PMID- 19152374
TI  - Targeted transduction of CD34+ hematopoietic progenitor cells in nonpurified
      human mobilized peripheral blood mononuclear cells.
AB  - BACKGROUND: Conventional gene-therapy applications of hematopoietic stem cells
      (HSCs) involve purification of CD34+ progenitor cells from the mobilized
      peripheral blood, ex vivo transduction of the gene of interest into them, and
      reinfusion of the transduced CD34+ progenitor cells into patients. Eliminating
      the process of purification would save labor, time and money, while enhancing
      HSCs viability, transplantability and pluripotency. Lentiviral vectors have been
      widely used in gene therapy because they infect both dividing and nondividing
      cells and provide sustained transgene expression. One of the exceptions to this
      rule is quiescent primary lymphocytes, in which reverse transcription of viral
      DNA is not completed. METHODS: In the present study, we tested the possibility of
      targeting CD34+ progenitor cells within nonpurified human mobilized peripheral
      blood mononuclear cells (mPBMCs) utilizing vesicular stomatitis virus G (VSV-G)
      pseudotyped lentiviral vectors, based on the assumption that the CD34+ progenitor
      cells would be preferentially transduced. To further enhance the specificity of
      vector transduction, we also examined utilizing a modified Sindbis virus envelope
      (2.2) pseudotyped lentiviral vector, developed in our laboratory, that allows
      targeted transduction to specific cell receptors via antibody recognition.
      RESULTS: Both the VSV-G and 2.2 pseudotyped vectors achieved measurable results
      when they were used to target CD34+ progenitor cells in nonpurified mPBMCs.
      CONCLUSIONS: Overall, the data obtained demonstrate the potential of ex vivo
      targeting of CD34+ progenitor cells without purification.

PMID- 19152375
TI  - Expression and homology modelling of sterol 14alpha-demethylase of Magnaporthe
      grisea and its interaction with azoles.
AB  - BACKGROUND: Magnaporthe grisea (Hebert) ME Barr infection is one of the most
      serious diseases for cultivated rice in the world. Sterol 14alpha-demethylase
      (CYP51) is an important drug target for microbial pathogenic infections. To
      exploit specific and effective fungicides for M. grisea better, the authors have
      analysed the characteristics of interaction between sterol 14alpha-demethylase
      from M. grisea (MGCYP51) and azoles. MGCYP51 with truncation of N-terminal
      residues was cloned and expressed in E. coli, difference binding spectra of
      MGCYP51 induced by addition of four commercial azoles were determined and
      molecular modelling of MGCYP51 based on the crystal structure of Mycobacterium
      tuberculosis Lehmann & Newman and docking with the azoles were performed.
      RESULTS: The affinity of the azoles for MGCYP51 was positively correlated with
      their hydrophobicity. Amino acid residues Tyr112, Phe120, Phe220, His308 and
      Phe497 of MGCYP51, forming a large hydrophobic cavity, are the key residues
      interacting with azole fungicides. Furthermore, Phe220 and Phe497 are fungus and
      species specific respectively. CONCLUSION: The results suggest that the more
      potent azole fungicides for MGCYP51 should possess more hydrophobic groups
      interacting with residues Phe220 and Phe497.

PMID- 19152376
TI  - The effect of salt content on the structure of iota-carrageenan systems: (23)Na
      DQF NMR and rheological studies.
AB  - (23)Na NMR spectroscopy has been used to study the effects of Na(+) ion
      concentrations on the structure of 1% (w/w) iota-carrageenan systems, a natural
      gelling polysaccharide used as a thickener in the food industry. Rheological and
      (23)Na T(1) relaxation time measurements revealed that gel formation correlates
      with decreases in ion mobility over the range of 0-3% (w/w) sodium content.
      (23)Na single-quantum (SQ) and double-quantum-filtered (DQF) NMR experiments
      performed on these systems provided evidence for a 'bound' sodium ion fraction in
      a specifically ordered environment. These results have allowed us to propose a
      model for the carrageenan gelation mechanism in the presence of Na(+) ions.

PMID- 19152377
TI  - Application of a (1)H delta-resolved 2D NMR experiment to the visualization of
      enantiomers in chiral environment, using sample spatial encoding and selective
      echoes.
AB  - We present the application of a 2D broadband homodecoupled proton NMR experiment
      to the visualization of enantiomers. In a chiral environment, the existence of
      diastereoisomeric intermolecular interactions can yield-generally slight
      variations of proton chemical shifts from one enantiomer to another. We show that
      this approach, which relies on a spatial encoding of the NMR sample, is
      particularly well suited to the analysis of enantiomeric mixtures, since it
      allows, within one single 2D experiment, to detect subtle chemical shift
      differences between enantiomers, even in the presence of several couplings. This
      sequence, which uses semiselective radio-frequency (rf) pulses combined to a z
      field gradient pulse, produces different selective echoes in various parts of the
      sample. The resulting homonuclear decoupling provides an original delta-resolved
      spectrum along the diagonal of the 2D map where it becomes possible to probe the
      chiral differentiation process through every proton site where the resulting
      variation in the chemical shift is detectable. We discuss the advantages and
      drawbacks of this approach, regarding other experiments which provide
      homodecoupled proton spectra. This methodology is applied to the observation of
      enantiomers of (1) ( +/- )2-methyl-isoborneol coordinated to europium (III)
      tris[3-(trifluoromethyl-hydroxymethylene)-(+)-camphorate] in isotropic solution,
      and (2) ( +/- )3-butyn-2-ol dissolved in a chiral liquid-crystal solvent, in
      order to show the robustness of this pulse sequence for a wide range of chiral
      samples.

PMID- 19152378
TI  - Consanguinity associated with increased risk for bipolar I disorder in Egypt.
AB  - We aimed to contrast rates of consanguinity among patients with bipolar I
      disorder (BP1) and controls in a population with customary consanguineous
      marriages (i.e., marriage between related individuals). Consanguinity increases
      risk for numerous monogenic and polygenic diseases. Whether the risk for BP1
      increases with consanguinity has not been investigated systematically. Two
      independent studies were conducted in Egypt: (1) Case-control study 93 patients
      with BP1, 90 screened adult control individuals, and available parents. The
      inbreeding coefficient/consanguinity rate was estimated in two ways: using 64 DNA
      polymorphisms ("DNA-based" rate); and from family history data ("self report");
      (2) Epidemiological survey: total of 1,584 individuals were screened, from whom
      self-reported consanguinity data were obtained for identified BP1 cases (n = 35)
      and 150 randomly selected, unaffected control individuals. DNA-based
      consanguinity rates showed significant case-control differences (P = 0.0039).
      Self-reported consanguinity rates were also elevated among BP1 patients in both
      samples (Study #1 OR = 2.66, 95% confidence intervals, CI: 1.34, 5.29; Study #2:
      OR = 4.64, 95% CI: 2.01, 10.34). In conclusion, two independent, systematic
      studies indicate increased consanguinity among Egyptian BP1 patients in the Nile
      delta region. Self-reported estimates of consanguinity are bolstered by DNA-based
      estimates, and both show significant case-control differences for BP1.

PMID- 19152380
TI  - Inappropriate cytotoxicity measurements.

PMID- 19152379
TI  - Ground plan of the insect mushroom body: functional and evolutionary
      implications.
AB  - In most insects with olfactory glomeruli, each side of the brain possesses a
      mushroom body equipped with calyces supplied by olfactory projection neurons.
      Kenyon cells providing dendrites to the calyces supply a pedunculus and lobes
      divided into subdivisions supplying outputs to other brain areas. It is with
      reference to these components that most functional studies are interpreted.
      However, mushroom body structures are diverse, adapted to different ecologies,
      and likely to serve various functions. In insects whose derived life styles
      preclude the detection of airborne odorants, there is a loss of the antennal
      lobes and attenuation or loss of the calyces. Such taxa retain mushroom body
      lobes that are as elaborate as those of mushroom bodies equipped with calyces.
      Antennal lobe loss and calycal regression also typify taxa with short nonfeeding
      adults, in which olfaction is redundant. Examples are cicadas and mayflies, the
      latter representing the most basal lineage of winged insects. Mushroom bodies of
      another basal taxon, the Odonata, possess a remnant calyx that may reflect the
      visual ecology of this group. That mushroom bodies persist in brains of
      secondarily anosmic insects suggests that they play roles in higher functions
      other than olfaction. Mushroom bodies are not ubiquitous: the most basal living
      insects, the wingless Archaeognatha, possess glomerular antennal lobes but lack
      mushroom bodies, suggesting that the ability to process airborne odorants
      preceded the acquisition of mushroom bodies. Archaeognathan brains are like those
      of higher malacostracans, which lack mushroom bodies but have elaborate olfactory
      centers laterally in the brain.

PMID- 19152382
TI  - Molecular cytogenetic evaluation of the mechanism of micronuclei formation
      induced by camptothecin, topotecan, and irinotecan.
AB  - We used the conventional bone marrow micronucleus test complemented with the
      fluorescent in situ hybridization with the minor satellite DNA probe to
      investigate the mechanisms of induction of micronuclei in mice treated with
      camptothecin and its clinical antineoplastic analogues topotecan and irinotecan.
      All experiments were performed with male Swiss albino mice. Single doses of 1
      mg/kg camptothecin or 0.6 mg/kg topotecan were injected intraperitoneally and
      bone marrow was sampled at 30 hr (camptothecin) or 24 hr (topotecan) after
      treatment. A dose of 60 mg/kg irinotecan was injected intravenously, once every
      fourth day for 13 days and bone marrow was sampled 24 hr after the last
      treatment. In animals treated with camptothecin, a total of 1.07% micronuclei
      were found and 70% of them were centromere-negative, indicating their formation
      by DNA strand breaks and reflecting the predominant clastogenic activity of
      camptothecin. Exposure to topotecan and irinotecan yielded 1.71 and 0.83%
      micronuclei, respectively. About 52.7 and 48.8% of the induced micronuclei,
      respectively, were centromere-positive, indicating their formation by whole
      chromosomes and reflecting the aneugenic activity of both compounds.
      Correspondingly, about 47.3 and 51.2% of the induced micronuclei, respectively
      were centromere-negative, demonstrating that topotecan and irinotecan not only
      induce chromosome loss but also DNA strand breaks. Both the clastogenic and
      aneugenic potential of these drugs can lead to the development of secondary
      tumors and abnormal reproductive outcomes. Therefore, the clinical use of these
      agents must be weighed against the risks of secondary malignancies in cured
      patients and persistent genetic damage of their potential offspring.

PMID- 19152381
TI  - Chlorophyllin significantly reduces benzo[a]pyrene-DNA adduct formation and
      alters cytochrome P450 1A1 and 1B1 expression and EROD activity in normal human
      mammary epithelial cells.
AB  - We hypothesized that chlorophyllin (CHLN) would reduce benzo[a]pyrene-DNA (BP
      DNA) adduct levels. Using normal human mammary epithelial cells (NHMECs) exposed
      to 4 microM BP for 24 hr in the presence or absence of 5 microM CHLN, we measured
      BP-DNA adducts by chemiluminescence immunoassay (CIA). The protocol included the
      following experimental groups: BP alone, BP given simultaneously with CHLN
      (BP+CHLN) for 24 hr, CHLN given for 24 hr followed by BP for 24 hr (preCHLN,
      postBP), and CHLN given for 48 hr with BP added for the last 24 hr (preCHLN,
      postBP+CHLN). Incubation with CHLN decreased BPdG levels in all groups, with 87%
      inhibition in the preCHLN, postBP+CHLN group. To examine metabolic mechanisms, we
      monitored expression by Affymetrix microarray (U133A), and found BP-induced up
      regulation of CYP1A1 and CYP1B1 expression, as well as up-regulation of groups of
      interferon-inducible, inflammation and signal transduction genes. Incubation of
      cells with CHLN and BP in any combination decreased expression of many of these
      genes. Using reverse transcription real time PCR (RT-PCR) the maximal inhibition
      of BP-induced gene expression, >85% for CYP1A1 and >70% for CYP1B1, was observed
      in the preCHLN, postBP+CHLN group. To explore the relationship between
      transcription and enzyme activity, the ethoxyresorufin-O-deethylase (EROD) assay
      was used to measure the combined CYP1A1 and CYP1B1 activities. BP exposure caused
      the EROD levels to double, when compared with the unexposed controls. The CHLN
      exposed groups all showed EROD levels similar to the unexposed controls.
      Therefore, the addition of CHLN to BP-exposed cells reduced BPdG formation and
      CYP1A1 and CYP1B1 expression, but EROD activity was not significantly reduced.

PMID- 19152383
TI  - Structural motifs modulating the carcinogenic risk of aromatic amines.
AB  - The structure alerts (SA) for carcinogenicity/mutagenicity are a repository of
      the science on chemical biological interactions; in addition, they have a crucial
      role in practical applications for risk assessment. In predictive toxicology, it
      is crucial that knowledge of SAs is accompanied by knowledge of the structural
      motifs that modulate their effects. Recently, we have compiled an updated list of
      SAs implemented in the expert system Tox-tree 1.50 (open source, freely
      available). These SAs are aimed at discriminating between active and inactive
      chemicals, and include only modulating factors with a high probability of
      eliminating completely the effect of the SA. Here we have examined the factors
      that modulate carcinogenic potency: this is an additional piece of information
      that can have a role in fine-tuning a risk assessment. The case study selected is
      the carcinogenic potential of the aromatic amines in rats and mice. As the
      carcinogenic potency of these compounds is different in mice and rats
      (correlation coefficient = 0.546), there are both agreements and differences in
      the pattern of these motifs. Differences are observed mainly for the motifs that
      decrease the carcinogenic potency of aromatic amines. In mice, substitutions
      ortho and meta to the amino group tend to decrease the potency, as well as -NO(2)
      in any position. In rats, these motifs affect the potency to a more limited
      extent. On the other hand, increasing effects are quite similar in the two
      animals and are exerted mainly by additional rings, tricyclic systems, five
      numbered rings, and N-heteroaromatic systems.

PMID- 19152384
TI  - Evidence for an interaction of schizophrenia susceptibility loci on chromosome
      6q23.3 and 10q24.33-q26.13 in Arab Israeli families.
AB  - A genome scan for schizophrenia related loci in Arab Israeli families by Lerer et
      al. [Lerer et al. (2003); Mol Psychiatry 8:488-498] detected significant evidence
      for linkage at chromosome 6q23. Subsequent fine mapping [Levi et al. (2005); Eur
      J Hum Genet 13:763-771], association [Amann-Zalcenstein et al. (2006); Eur J Hum
      Genet 14:1111-1119] and replication studies [Ingason et al. (2007); Eur J Hum
      Genet 15:988-991] identified AHI1 as a putative susceptibility gene. The same
      genome scan revealed suggestive evidence for a schizophrenia susceptibility locus
      in the 10q23-26 region. Genes at these two loci may act independently in the
      pathogenesis of the disease in our homogeneous sample of Arab Israeli families or
      may interact with each other and with other factors in a common biological
      pathway. The purpose of our current study was to test the hypothesis of genetic
      interaction between these two loci and to identify the type of interaction
      between them. The initial stage of our study focused on the 10q23-q26 region
      which has not been explored further in our sample. The second stage of the study
      included a test for possible genetic interaction between the 6q23.3 locus and the
      refined 10q24.33-q26.13 locus. A final candidate region of 19.9 Mb between
      markers D10S222 (105.3 Mb) and D10S587 (125.2 Mb) was found on chromosome 10 by
      non-parametric and parametric linkage analyses. These linkage findings are
      consistent with previous reports in the same chromosomal region. Two-locus
      multipoint linkage analysis under three complex disease inheritance models
      (heterogeneity, multiplicative, and additive models) yielded a best maximum LOD
      score of 7.45 under the multiplicative model suggesting overlapping function of
      the 6q23.3 and 10q24.33-q26.13 loci.

PMID- 19152385
TI  - Protein instability during HIC: evidence of unfolding reversibility, and apparent
      adsorption strength of disulfide bond-reduced alpha-lactalbumin variants.
AB  - A two-conformation, four-state model has been proposed to describe protein
      adsorption and unfolding behavior on hydrophobic interaction chromatography (HIC)
      resins. In this work, we build upon previous study and application of a four
      state model to the effect of salt concentration on the adsorption and unfolding
      of the model protein alpha-lactalbumin in HIC. Contributions to the apparent
      adsorption strength of the wild-type protein from native and unfolded
      conformations, obtained using a deuterium labeling technique, reveal the free
      energy change and kinetics of unfolding on the resin, and demonstrate that
      surface unfolding is reversible. Additionally, variants of alpha-lactalbumin in
      which one of the disulfide bonds is reduced were synthesized to examine the
      effects of conformational stability on apparent retention. Below the melting
      temperatures of the wild-type protein and variants, reduction of a single
      disulfide bond significantly increases the apparent adsorption strength
      (approximately 6-8 kJ/mol) due to increased instability of the protein. Finally,
      the four-state model is used to accurately predict the apparent adsorption
      strength of a disulfide bond-reduced variant.

PMID- 19152386
TI  - A family-based association study of the glutamate transporter gene SLC1A1 in
      obsessive-compulsive disorder in 378 families.
AB  - SLC1A encodes the neuronal and epithelial glutamate transporter and was
      previously tested as a candidate for obsessive-compulsive disorder (OCD) by
      several research groups. Recently, three independent research groups reported
      significant association findings between OCD and several genetic variants in
      SLC1A1. This study reports the results from a family-based association study,
      which examined the association between 13 single nucleotide polymorphisms (SNPs)
      within or in proximity to the SLC1A1 gene. Although we did not replicate
      association findings for those significant SNPs reported by previous studies, our
      study indicated a strong association signal with the SNP RS301443 (P-value =
      0.000067; Bonferroni corrected P-value = 0.0167) under a dominant model, with an
      estimated odds ratio of 3.5 (confidence interval: 2.66-4.50). Further, we
      conducted single SNP analysis after stratifying the full data set by the gender
      status of affected in each family. The P-value for RS301443 in families with the
      male affected was 0.00027, and the P-value in families with female affected was
      0.076. The fact that we identified a signal which was not previously reported by
      the other research groups may be due to differences in study designs and sample
      ascertainment. However, it is also possible that this significant SNP may be part
      of a regulator for SLC1A1, given that it is roughly 7.5 kb away from the boundary
      of the SLC1A1 gene. However, this potential finding needs to be validated
      biologically. Further functional studies in this region are planned by this
      research group.

PMID- 19152388
TI  - Selective propene epoxidation on immobilized au(6-10) clusters: the effect of
      hydrogen and water on activity and selectivity.
AB  - Epoxidation made easy: Subnanometer gold clusters immobilized on amorphous
      alumina result in a highly active and selective catalyst for propene epoxidation.
      The highest selectivity is found for gas mixtures involving oxygen and water,
      thus avoiding the use of hydrogen. Ab initio DFT calculations are used to
      identify key reaction intermediates and reaction pathways. The results confirm
      the high catalyst activity owing to the formation of propene oxide metallacycles.
      Al green, Au yellow, O red, and C gray.

PMID- 19152387
TI  - Genetic variation in 5HTTLPR is associated with emotional resilience.
AB  - Emotional resilience can be defined as the ability to maintain healthy and stable
      levels of psychological functioning in the wake of stress and trauma. Although
      genes that contribute to psychopathology (often in interaction with environmental
      stressors) are being detected with increasing consistency, genes that influence
      resilience to stress have been less studied. In this study, 423 undergraduate
      college students completed a psychometrically sound 10-item self-report measure
      of resilience (CDRISC-10) and provided blood for DNA. Linear and logistic
      regression analyses were used to model relationships between the serotonin
      transporter promoter polymorphism (5HTTLPR) and CDRISC-10 scores and categories,
      respectively. CDRISC-10 scores were normally distributed (mean 26.17, SD 5.88
      [range 5-40]). In models adjusting for ancestry proportion scores (to mitigate
      confounding by population stratification) and other covariates, each copy of the
      "s" allele of 5HTTLPR was associated with approximately 1-point lower CDRISC-10
      score. Each copy of the "s" allele was associated with increased (adjusted OR =
      1.53, 95% CI 1.06-2.21, P = 0.024) odds of being in the low resilient category
      (>1 SD below the mean), compared to being homozygous for the "l" allele. These
      findings suggest that variation in 5HTTLPR is associated with individual
      differences in emotional resilience, defined as an individual's ability to
      withstand and bounce back from stress. This relationship may explain the
      frequently observed interaction between 5HTTLPR and life stressors in predicting
      adverse mental health outcomes (e.g., depressive symptoms). Replication is
      needed, in concert with identification of other genes that influence emotional
      resilience and related phenotypes.

PMID- 19152390
TI  - Plug-based microfluidics with defined surface chemistry to miniaturize and
      control aggregation of amyloidogenic peptides.
AB  - Small with control: For miniaturization of protein aggregation experiments the
      interfacial chemistry must be controlled to avoid protein aggregation caused by
      interfacial adsorption. Plug-based microfluidics with defined surface chemistry
      (see schematic picture) can then be used to perform hundreds of aggregation
      experiments with volume-limited samples, such as cerebrospinal fluid from mice.

PMID- 19152391
TI  - Taming the highly reactive oxonium ion.
AB  - 'Onium rings: Incorporation of the trivalent oxygen atom as a structural element
      within the tricyclic core of 1-3 imparts unprecedented stability to this
      "extraordinary" class of tertiary oxonium ions. Cation 1 is the least reactive
      and can be refluxed in water for 72 hours with no noticeable decomposition.

PMID- 19152392
TI  - Synthesis and biological activity of argiotoxin 636 and analogues: selective
      antagonists for ionotropic glutamate receptors.
AB  - More discerning than the parent: Analogues of the polyamine toxin argiotoxin 636
      (shown docked in the ion channel of an ionotropic glutamate (iGlu) receptor; N
      blue, O red) distinguish subtypes of iGlu receptors. Depending on which of the
      two internal amine groups is replaced with a methylene group, the analogue
      inhibits one or other of two receptor subtypes as potently as the natural
      compound, which itself inhibits both subtypes nonselectively.

PMID- 19152393
TI  - Increased detection of HBV DNA in HBsAg-positive and HBsAg-negative South African
      HIV/AIDS patients enrolling for highly active antiretroviral therapy at a
      Tertiary Hospital.
AB  - This retrospective study investigated the prevalence of hepatitis B virus (HBV)
      in 192 stored sera from human immunodeficiency virus (HIV) positive South African
      patients initiating antiretroviral therapy (ART), and explored the implications
      of HBV-HIV co-infection on laboratory diagnosis of HBV. HBV serology (HBsAg, anti
      HBs and anti-HBc) and nested HBV PCR assays targeting the HBV polymerase gene
      were performed, with HBV DNA positive samples being quantified with Cobas Taqman
      HBV test 48 assay (Roche Diagnostics). The study found that 63% (121/192) of
      patients had past or present HBV infection, and 40.6% (78/192) had detectable HBV
      DNA. Also, 22.9% (44/192) of patients were HBsAg positive and HBV DNA positive,
      while 23% (34/148) of HBsAG negatives had occult HBV infections. Of the 78 HBV
      DNA positive samples, 62.8% had viral loads ranging from 10(2) to > or =10(8)
      IU/ml, and 37.2% had HBV viral loads <200 IU/ml. There was a statistically
      significant positive association between HBsAg-positivity and high viral loads,
      with 27% (12/44) of HBsAg positives having HBV viral loads between 10(4) and > or
      =10(8) IU/ml, compared to only 5.9% (2/34) of HBsAg negatives (relative risk:
      4.64; 95% confidence interval: 1.11, 19.35; chi-square P-value = 0.015). The
      study shows that the majority of HIV/AIDS patients initiating ART have either
      acute or chronic HBV infections, and further confirms that HIV remains a risk
      factor for occult HBV infections in South African patients as previously shown.
      The findings strongly support HBV screening in all HIV-positive patients
      initiating ART in South Africa, considering that current ART regimens include
      drugs with anti-HBV activity (e.g., lamivudine).

PMID- 19152394
TI  - Identification of mutations in a temperature-sensitive mutant (tsm5) of murine
      cytomegalovirus using complementary genome sequencing.
AB  - Identification of mutations in mutants derived chemically is a difficult and
      relatively random process. NimbleGen Comparative Genome Sequencing (CGS) was
      assessed as an inexpensive, rapid method of identifying mutations in the
      temperature-sensitive mutant tsm5 of the K181 (Birmingham) variant of murine
      cytomegalovirus (MCMV). This genome resequencing approach requires an established
      genome sequence as a reference. Comparison of tsm5 and the K181 (Birmingham)
      variant with the published K181 (Perth) MCMV genomic sequence revealed a total of
      10 synonymous and 15 non-synonymous SNPs in tsm5 and 14 of the latter were
      confirmed by sequencing. Thus, while CGS cannot be relied upon to identify
      correctly all mutations it was helpful for identifying a large number of
      mutations for further investigation that could contribute to the ts phenotype of
      tsm5.

PMID- 19152395
TI  - Severity and age of rotavirus diarrhea, but not socioeconomic conditions, are
      associated with rotavirus seasonality in Venezuela.
AB  - Rotavirus (RV) epidemiology presents differences between developing and developed
      countries among which are seasonality, age at first infection, variability of
      strain in circulation and severity of disease. Since, in Venezuela, we have
      distinct seasonal patterns of RV occurrence, we examined the epidemiological
      profile of RV disease associated to these differences by analyzing data from
      previous studies conducted in Venezuela. Data were collected from children <5
      years of age with diarrhea seen in six hospitals located in five cities. Socio
      demographic and clinical characteristics of RV illness were analyzed according to
      RV identification by ELISA assay and the seasonal patterns of RV circulation
      (marked versus minimal seasonality). A total of 6,742 episodes of diarrhea (1,820
      rotavirus positive and 4,922 rotavirus negative) were evaluated: 1,951 in
      Caracas, Cumana and Pto. Ordaz (minimal seasonality) and 4,791 in Merida and
      Valencia (marked seasonality). Mean age (months) of children with RV was 8.14 +/-
      6.74 and 12.21 +/- 9.62 (P < 0.0001) in areas with minimal and marked
      seasonality, respectively. RV disease was more frequent (33% vs. 24%; OR = 1.536;
      95% CI: 1.36-1.73), more severe (dehydration: 64% vs. 29%; OR = 4.436; 95% CI:
      3.61-5.44) and more common in infants than in older children (79% vs. 60%; OR =
      2.521; 95% CI: 2.01-3.14) in cities with minimal seasonality than in those with
      marked seasonality. Socioeconomic conditions were not associated with
      seasonality. In environments with minimal seasonality, children are infected with
      RV at younger ages and the disease is more severe regardless of malnutrition and
      poverty.

PMID- 19152396
TI  - Polymorphisms at GLUT1 gene are not associated with the development of TSP/HAM in
      Brazilian HTLV-1 infected individuals and the discovery of a new polymorphism at
      GLUT1 gene.
AB  - The development of HTLV-1 associated clinical manifestations, such as TSP/HAM and
      ATLL, occur in 2-4% of the infected population and it is still unclear why this
      infection remains asymptomatic in most infected carriers. Recently, it has been
      demonstrated that HTLV uses the Glucose transporter type 1 (GLUT1) to infect T
      CD4(+) lymphocytes and that single nucleotide polymorphisms (SNP) in the GLUT1
      gene are associated with diabetic nephropathy in patients with diabetes mellitus
      in different populations. These polymorphisms could contribute to a higher GLUT1
      protein expression on cellular membrane, facilitating the entry of HTLV and its
      transmission cell by cell. This could result in a higher provirus load and
      consequently in the development of TSP/HAM. To evaluate the role of GLUT1 gene
      polymorphisms in the development of TSP/HAM in HTLV-1 infected individuals, the
      g.22999G > T, g.15339T > C and c.-2841A > T sites were analyzed by PCR/RFLP or
      sequencing in 244 infected individuals and 102 normal controls. The proviral load
      of the HTLV-1 infected patients was also analyzed using Real Time Quantitative
      PCR. Genotypic and allelic frequencies of the three sites did not differ
      significantly between controls and HTLV-1 infected individuals. There was no
      difference in genotypic and allelic distributions among patients as to the
      presence or absence of HTLV-1 associated clinic manifestations. As regards the
      quantification of the provirus load, we observed a significant reduction in the
      asymptomatic individuals compared with the oligosymptomatic and TSP/HAM
      individuals. These results suggest that g.22999G > T, g.15339T > C, and c.-2841A
      > T SNP do not contribute to HTLV-1 infection nor to the genetic susceptibility
      of TSP/HAM in Brazilian HTLV-1 infected individuals.

PMID- 19152397
TI  - Occult hepatitis B in persons infected with HIV is associated with low CD4 counts
      and resolves during antiretroviral therapy.
AB  - Occult hepatitis B virus (HBV) is defined by the presence of plasma HBV DNA in
      individuals with HBV core antibodies (anti-HBc), but without HBV surface antigen
      (HBsAg). The prevalence of occult HBV in HIV-infected patients remains
      controversial, and the risk factors, clinical significance and effect of highly
      active antiretroviral therapy (HAART) are unknown. The aim of this study was to
      determine prevalence, risk factors, and clinical significance of occult HBV in
      HIV-infected patients and to evaluate the effect of HAART. Plasma HBV DNA levels
      were determined in 191 HIV positive, antiretroviral naive patients, who were anti
      HBc positive and HBsAg negative. Quantitative HBV DNA was determined using a
      Taqman real-time nested PCR. Additionally, plasma HIV RNA levels, CD4 cell
      counts, anti-HBs-antibodies, anti-HCV-antibodies, ALT, AST, and gammaGT were
      determined. Occult HBV (a plasma HBV DNA level >50 copies/ml) was detected in
      9/191 (4.7%) of the patients. Among 45 anti-HBs-negative patients (isolated anti
      HBc positive), the prevalence was 11.1%. Patients with occult HBV had
      significantly lower CD4 count compared to anti-HBc-positive/HBsAg negative/HBV
      DNA-negative patients (105 +/- 157 (median +/- SD) vs. 323 +/- 299 cells/mm(3), P
      = 0.019). When HAART (including lamivudine) was initiated in the patients with
      occult HBV, HBV DNA was no longer detectable in any of the patients during 3
      years of follow-up. In conclusion, occult HBV was associated with low CD4 counts
      and may be viewed as opportunistic reactivation of HBV that resolves as a
      consequence of HAART induced immune reconstitution and/or the effect of
      lamivudine.

PMID- 19152398
TI  - Seasonal shifts of group A rotavirus strains as a possible mechanism of
      persistence in the human population.
AB  - This article demonstrates how the seasonal predominance of a new rotavirus strain
      in Asuncion, Paraguay is correlated with a wide spectrum of age groups of
      children infected in that given season. Therefore, this study provides new
      evidence to support the idea that seasonal shift of rotavirus strains is a
      possible mechanism used by the virus to evade herd immunity (acquired by the
      population due to previous infections) and, thus, ultimately persist in that
      population.

PMID- 19152399
TI  - Prognostic factors of long-term CD4+count-guided interruption of antiretroviral
      treatment.
AB  - Aim of the study was to determine predictors of the duration of antiretroviral
      treatment interruption in patients infected with HIV. This pilot prospective,
      open-label, multicenter trial comprised 62 HIV-seropositive subjects who decided
      voluntarily to interrupt therapy after two or more years of successful HAART. The
      primary end-point was the time to patients being free of therapy before reaching
      a CD4+ cell count < or =350/microl. Fifteen of 62 patients remained in treatment
      interruption for more than 180 days. Patients restarting therapy had higher HIV
      DNA levels (P = 0.05), were treated more frequently with NNRTI-drugs (P = 0.02),
      had a shorter period of HAART (P = 0.046), and lower CD4+ cell counts after day
      14 of interruption of treatment (P = 0.04). Multivariate regression analysis
      showed that less than 323 baseline proviral HIV-DNA cp/10(6) PBMCs and more than
      564 CD4 cells/microl at day 14 after interruption were associated independently
      with a reduced risk of restarting treatment (P = 0.041 and P = 0.012,
      respectively). A score based on CD4+ cell counts at nadir, at baseline, at week 2
      of treatment interruption, and on baseline HIV-DNA values can identify patients
      with a prolonged period free safely of treatment.

PMID- 19152400
TI  - Long-term follow-up of patients with hepatitis C with a normal alanine
      aminotransferase.
AB  - An attempt was made to identify factors influencing the cumulative probability of
      an increased alanine aminotransferase (ALT) level and hepatocarcinogenesis in
      hepatitis C patients with a normal ALT level initially. A total of 398
      consecutive patients with a normal ALT level initially for 6 months or more and
      follow-up period longer than 3 years during the period January 1995 to December
      2004 were included. Patients were classified by ALT level into three groups:
      Group A (3-20 IU/L), Group B (21-30 IU/L), and Group C (31-35 IU/L). Factors
      associated with the cumulative probability of increased ALT level and
      hepotocarcinogenesis were evaluated. Women in groups B and C and men in Group C
      showed high cumulative probabilities of increased ALT levels. Factors associated
      with increased ALT were a high ALT level (Group B, relative risk; 1.758 [95%
      confidence interval: 1.290-2.392], P < 0.001, Group C, 3.328 [2.256-4.909], P <
      0.001), high lactate dehydrogenase level (2.352 [1.445-3.829], P = 0.001), or low
      total cholesterol level (1.957 [1.330-2.882], P = 0.001). Factors associated with
      incidence of hepatocellular carcinoma were increased age (3.088 [1.025-9.308], P
      = 0.045), high ALT level (Group C, 5.803 [1.530-22.066], P = 0.010), and high
      total bilirubin level (8.309 [2.235-30.888], P = 0.002). In patients with
      hepatitis C with a normal ALT level initially, an ALT level of 21-35 IU/L is a
      risk factor for an increased ALT level and hepatocarcinogenesis.

PMID- 19152401
TI  - Prevalence and type distribution of high-risk human papillomavirus infection in
      women undergoing voluntary cervical cancer screening in Italy.
AB  - The aim of this survey was to assess the prevalence and distribution of oncogenic
      human papillomavirus (HPV) genotypes in women who underwent screening for
      cervical cancer in Italy. The correlation of genotypes with the cytological
      results was also evaluated. Cervical samples were collected from 9,947 self
      referring women for cervical cancer screening. Participants were screened by
      liquid-based cytology and high-risk HPV testing using the Hybrid Capture 2 test.
      Positive samples were genotyped by PCR. Samples (1,474; 14.8%) were positive for
      high-risk HPV. The prevalence was 29.4% in the 15-19 years-group, decreasing
      progressively to 6.1% at 50-54 years of age and increasing to 12.2% in those aged
      over 65 years. HPV 16 was the genotype detected most frequently followed by HPV
      31, HPV 18, HPV 56, and HPV 51. HPV 16 or 18 were present in 4% of women with
      normal cytology and both were detected contemporarily in only 14 women. Twenty
      two percent of atypical squamous cells, 26% of low-grade and 56% of high-grade
      squamous intraepithelial lesions at cytology were positive for HPV 16 and/or 18.
      The prevalence of HPV infection in Italy is in agreement with that reported
      worldwide. HPV 16 was the prevalent genotype. The concomitant infection with HPV
      16 and HPV 18 (vaccine targets) was found rarely. Apart from HPV 16 and 18, there
      was a substantial presence of HPV genotypes against which the vaccines available
      currently have shown cross-protection efficacy. The findings of this study may
      contribute to reliable predictions on the potential efficacy of an HPV vaccine in
      clinical practice.

PMID- 19152402
TI  - Successful valganciclovir treatment of post-transplant cytomegalovirus infection
      in the presence of UL97 mutation N597D.
AB  - Mutations in the human cytomegalovirus (CMV) UL97 protein kinase are the most
      common mechanism of ganciclovir (GCV) resistance in the clinical setting. A CMV
      strain with a previously unrecognized UL97 mutation N597D was identified in the
      blood of a heart transplant recipient who experienced a persistent CMV infection
      with high viral loads accompanying pain and fever while receiving valganciclovir
      (valGCV) therapy. The N597D mutation was transferred by mutagenesis to an
      antiviral sensitive CMV strain for analysis of antiviral susceptibility by
      standardized phenotypic assay. Recombinant phenotyping showed N597D conferred a
      less than twofold increase in GCV IC(50) compared to the sensitive control
      strain. Despite the presence of this mutation, valGCV eventually resolved the
      infection after 6 weeks of therapy. A subsequent CMV reactivation was also
      responsive to valganciclovir. This case illustrates the diversity of UL97
      mutations in the codon segment 590-607 usually associated with GCV resistance,
      with some mutations producing minimal levels of resistance that do not preclude a
      therapeutic response to the drug. Accurate interpretation of genotypic test
      results ultimately requires experimental determination of the level of resistance
      conferred by newly discovered UL97 mutations.

PMID- 19152403
TI  - Analysis of gene transcription in sera during chronic hepatitis C infection.
AB  - Alternative, non-invasive techniques are necessary to monitor the progression of
      liver disease during chronic hepatitis C. Firstly, because serum is the most
      accessible material for studies using qPCR in microplates, gene transcription was
      compared in 219 selected genes involved in the pathogenesis of hepatitis C virus
      (HCV) infection between sera, PBMCs and liver samples collected simultaneously
      from five patients infected chronically. Secondly, using sera, gene profiles were
      compared between HCV-infected patients (n = 10) and healthy controls (n = 10). In
      addition, the influence of alcohol intake was examined in patients infected with
      HCV genotype-1. Firstly, amplifiable mRNAs were obtained in all samples. After
      amplification, significant correlations were observed between: liver versus
      serum; liver versus PBMCs; and serum versus PBMCs (r(2) = 0.37, r(2) = 0.54, r(2)
      = 0.49, respectively). A comparison of gene transcription by gene involved in T-
      and B-cell markers, adhesion molecules, apoptosis, liver matrix turnover and
      inflammation, revealed comparable, significant correlations between serum and
      liver, (r(2) = 0.30, r(2) = 0.60, r(2) = 0.51, r(2) = 0.51, r(2) = 0.26, and r(2)
      = 0.61 respectively). Secondly, a quantitative analysis of gene expression in
      sera between genotype-1b-infected patients and healthy controls revealed that 41
      genes involved closely in T-cell activation and apoptosis were over-expressed
      significantly in patients infected with HCV. In these patients, alcohol
      consumption was associated with an increased expression of six genes involved in
      the inflammatory response, together with a decrease of genes associated with
      dendritic cell function. It is concluded that in patients infected with HCV,
      serum can be used to evaluate expression of liver genes. Further prospective
      studies are clearly needed to validate the initial results and to define the
      relevant genes.

PMID- 19152404
TI  - Ultrasensitive assessment of residual HIV viraemia in HAART-treated patients with
      persistently undetectable plasma HIV-RNA: a cross-sectional evaluation.
AB  - Improvements in HIV-RNA assays have made accurate detection of as few as 2
      copies/ml possible. This study objective was the evaluation of ultrasensitive HIV
      RNA quantitation (beneath current threshold: 50 copies/ml) in patients receiving
      different antiretroviral regimens. A cross-sectional, ultrasensitive measurement
      of HIV-RNA levels (detection limit: 2.5 HIV-RNA copies/ml) was performed in 154
      HIV-1-infected patients receiving ARV therapy, all classed as full responders
      according to the 50 copies/ml cut-off. Patients were undergoing treatment with
      two nucleoside/nucleotide reverse transcriptase inhibitors (N/NtRTIs) plus
      nevirapine (NVP, n = 48), efavirenz (EFV, n = 57) or lopinavir/ritonavir (LPV/r,
      n = 49). Undetectable HIV-RNA (<2.5 copies/ml) occurred in 29/48 (60.4%), 24/57
      (42.1%) and 14/49 (28.6%) NVP, EFV and LPV/r recipients, respectively. Mean
      virological-suppression (<50 copies/ml) duration was 28.6 months (median = 22, SD
      = 17.8), and only in LPV/r recipients length of suppression was associated with
      significantly lower HIV-RNA levels (P = 0.015). Mean nadir CD4+ cell count of 270
      cells/mm(3) (median = 240, SD = 194.5) was significantly lower in the LPV/r arm
      (P < 0.001). Nadir CD4+ level correlated with virological suppression but had
      opposite trends between NVP (positive) and LPV/r (negative; two tailed P = 0.01).
      Logistic regression analysis showed NVP was the only independent factor
      associated with virologic suppression. NVP has demonstrated a distinct
      virological advantage at sub-clinical viral loads, possibly due to its greater
      penetration in extra-vascular compartments, warranting further investigation in
      the context of persistent low-level viraemia in long-term HAART.

PMID- 19152405
TI  - Accurate assessment of clinical nurses' work environments: response rate needed.
AB  - Improvement of hospital unit work environments is key to quality patient care,
      productivity, nurse retention, and job satisfaction. Accurate measurement of such
      environments is necessary prior to introduction and evaluation of improvement
      structures and strategies. Characteristics and attributes of work environments
      are group level phenomena. Accurate assessment of these phenomena requires survey
      response rates of sufficient size to ensure sample representativeness and data
      that can reliably be aggregated to group level. What is the sufficient response
      rate? This question was answered through psychometric testing of five random
      samples from the population of 23 M.D. Anderson Cancer Center clinical units that
      had 100% response rates on an environmental survey. Response rates of 40% or more
      had acceptable psychometric properties for unit-specific scales.

PMID- 19152406
TI  - Expression of macrophage inhibitory cytokine-1 in prostate cancer bone metastases
      induces osteoclast activation and weight loss.
AB  - BACKGROUND: Macrophage inhibitory cytokine-1 (MIC-1) belongs to the bone
      morphogenic protein/transforming growth factor-beta (BMP/TGF-beta) superfamily.
      Serum MIC-1 concentrations are elevated in patients with advanced prostate
      cancer. The effects of MIC-1 on prostate cancer bone metastases are unknown.
      METHODS: In vitro effects of MIC-1 on osteoblast differentiation and activity
      were analyzed with alkaline phosphatase and mineralization assays; osteoclast
      numbers were counted microscopically. MIC-1 effects on TLR9 expression were
      studied with Western blotting. Human Du-145 prostate cancer cells were stably
      transfected with a cDNA encoding for mature MIC-1 or with an empty vector. The in
      vivo growth characteristics of the characterized cells were studied with the
      intra-tibial model of bone metastasis. Tumor associated bone changes were viewed
      with X-rays, histology, and histomorphometry. Bone formation was assayed by
      measuring serum PINP. RESULTS: MIC-1 induced osteoblast differentiation and
      activity and osteoclast formation in vitro. These effects were independent of
      TLR9 expression, which was promoted by MIC-1. Both MIC-1 and control tumors
      induced mixed sclerotic/lytic bone lesions, but MIC-1 increased the osteolytic
      component of tumors. Osteoclast formation at the tumor-bone interface was
      significantly higher in the MIC-1 tumors, whereas bone formation was
      significantly higher in the control mice. At sacrifice, the mice bearing MIC-1
      tumors were significantly lighter with significantly smaller tumors. CONCLUSIONS:
      MIC-1 up-regulates TLR9 expression in various cells. MIC-1 stimulates both
      osteoblast and osteoclast differentiation in vitro, independently of TLR9. MIC-1
      over-expressing prostate cancer cells that grow in bone induce osteoclast
      formation and cachexia.

PMID- 19152407
TI  - A matched case-controlled study of 48 and 72 weeks of peginterferon plus
      ribavirin combination therapy in patients infected with HCV genotype 1b in Japan:
      amino acid substitutions in HCV core region as predictor of sustained virological
      response.
AB  - Substitution of amino acid (aa) 70 and 91 in the core region of HCV genotype 1b
      is a useful pretreatment predictor of efficacy of 48-week peginterferon (PEG-IFN)
      plus ribavirin (RBV) therapy. Here, we determined the efficacy of 72-week PEG
      IFN/RBV and the predictive factors to such therapy in a case-control study
      matched for sex, age, and periods from the start of treatment to initial point of
      HCV RNA-negative. We compared the treatment efficacy of 72-week regimen in 65
      patients with that of 48-week in 130 patients, who were infected with HCV
      genotype 1b and treated with PEG-IFN/RBV. They consisted mainly of late
      virological responders (LVR) (HCV RNA-positive at 12 weeks and negative at 24
      weeks after start of treatment). Sustained virological response (SVR) was
      achieved by 61.5% and 32.3% of patients of the 72- and 48-week groups,
      respectively, while non-virological response was noted in 9.2% and 29.2% of the
      respective groups. Multivariate analysis identified substitution of aa 70 and 91
      (Arg70 and/or Leu91) and duration of treatment (72-week) as independent
      parameters that significantly influenced SVR. For Arg70 and/or Leu91 of core
      region, SVR rate was significantly higher in 72- (68.0%) than 48-week group
      (37.8%). For wild-type of ISDR, SVR rate was significantly higher in 72- (61.2%)
      than in 48-week group (29.3%). We conclude that 72-week PEG-IFN/RBV improves SVR
      rate for LVR, especially those with Arg70 and/or Leu91 of core region or wild
      type of ISDR. Substitution of aa 70 and 91 is also a useful pretreatment
      predictor of response to 72-week PEG-IFN/RBV.

PMID- 19152408
TI  - Susceptibility of hepatitis B virus to lamivudine restored by resistance to
      adefovir.
AB  - Serial monotherapy and add-on regimes for treatment of chronic hepatitis B virus
      (HBV) infection may induce the accumulation of viral resistance mutations in
      patients, reducing the options for ongoing viral suppression. The induction of
      antiviral resistance by serial application of polymerase inhibitors does not
      necessarily imply that the subsequent combined use of the drugs will fail. Some
      HIV strains resistant to one polymerase inhibitor show increased susceptibility
      to another polymerase inhibitor. After failure of sequential lamivudine and
      adefovir monotherapy, two patients with hepatitis B changed to treatment with
      lamivudine plus adefovir and had renewed suppression of HBV. To study the
      mutational history of resistant HBV subpopulations in the two patients, a part of
      the HBV polymerase gene was amplified, cloned, sequenced, and analyzed for the
      presence of mutations, in sequential plasma samples. In both patients serial
      monotherapy caused the replacement in all HBV clones of wild-type virus by
      classical lamivudine resistant mutants (L180M and M204V/I), which were replaced
      subsequently by adefovir resistant mutants (A181V and N236T). When finally
      lamivudine was added to adefovir, the A181V adefovir mutation persisted in all
      clones and lamivudine-related mutations did not reappear. During 18 months of
      combination therapy, HBV-DNA levels decreased 10,000, respectively, 1,000-fold,
      despite the earlier resistance to lamivudine and adefovir. Although clinically
      insufficient, this effect indicates that HBV polymerase resistance mutations may
      be antagonistic, which is relevant if chronic HBV infection is to be treated by a
      combination of polymerase inhibitors.

PMID- 19152409
TI  - Association of lamivudine-resistant mutational patterns with the antiviral effect
      of adefovir in patients with chronic hepatitis B.
AB  - Adefovir has a potent antiviral activity as a rescue treatment against lamivudine
      resistant strains. The aim of this study was to assess the patterns of lamivudine
      resistant mutations and their influence on the virologic response to adefovir
      rescue therapy in patients with lamivudine-resistant chronic hepatitis B. Sixty
      seven patients with lamivudine-resistant chronic hepatitis B were treated with
      adefovir monotherapy. Baseline blood samples were analyzed for lamivudine
      resistant mutations via restriction fragment mass polymorphism. Virologic
      responses, ALT normalization and loss of HBeAg were assessed. Serum HBV DNA
      levels were measured using real-time PCR at baseline and 24 weeks of adefovir
      therapy. Of the 67 patients with chronic hepatitis B, 65 patients (97%) had
      lamivudine-resistant mutations in the YMDD motif [27 (41%) rtM204I, 22 (34%)
      rtM204V, and 16 (25%) rtM204I/V]. In addition to the YMDD mutations, the rtL180M,
      rtL80I, and rtV173L mutations were also present in 78%, 43%, and 11% of patients,
      respectively. The rtM204V mutation always accompanied rtL180M, and rtL80I was
      always observed in conjunction with rtM204I. Decrease in mean serum HBV did not
      differ between patients carrying the rtM204I versus rtM204V mutant at week 24 (
      3.3 vs. -3.3 log(10) copies/ml, respectively; P = 0.303). The presence of the
      rtL180M, rtL80I, and rtV173L did not significantly affect viral load reduction
      during adefovir administration. These results demonstrate that the rtL80I mutant
      is co-selected with rtM204I as a compensatory mutation in the same manner as
      rtL180M with rtM204V, and that adefovir shows similar antiviral efficacy against
      all of the evaluated patterns of lamivudine-resistant HBV mutations.

PMID- 19152410
TI  - Cell cycle perturbation in the hepatocytes of HCV core transgenic mice following
      common bile duct ligation is associated with enhanced p21 expression.
AB  - Hepatitis C virus (HCV) core protein has been reported to alter the cell cycle in
      vitro, but the data remain inconclusive, and in vitro experiments do not
      represent precisely events that occur in vivo, which may involve hepatic
      inflammation or regeneration. A group of double-transgenic mice carrying
      tetracycline transactivator (tTA) and HCV core that express conditionally the HCV
      core in the mature liver, and single-transgenic mice carrying only tTA were
      subjected to sham laparotomy, 43% partial hepatectomy, or common bile duct
      ligation. The cell cycle markers, including cyclin A, B1, D, E1, Mcm-2,
      phosphorylated histone 3 protein, Ki67, and p21Waf1/Cip1/Sdi1 (p21), were
      evaluated in liver samples obtained 3 days after the operation. No significant
      differences in the levels of any markers were observed between the double- and
      single-transgenic mice following sham laparotomy. Among the mice that underwent
      common bile duct ligation, the double-transgenic mice had lower levels of Ki67 (P
      = 0.0001), higher levels of cyclin D1 (P = 0.0001), and higher levels of p21
      expression than the single-transgenic mice. Among those that underwent partial
      hepatectomy, the double-transgenic mice had higher p21 expression levels, but no
      significant differences in the levels of any other markers were observed between
      the double- and single-transgenic mice. It is concluded that the HCV core alters
      the hepatocyte cell cycle in addition to inducing G1 arrest in vivo after common
      bile duct ligation, and is associated with enhanced p21 expression. This may
      account at least partially for the strong association between HCV-related
      hepatocarcinogenesis and hepatic inflammation/ fibrosis.

PMID- 19152411
TI  - Interaction between human papillomavirus type 5 E2 and polo-like kinase 1.
AB  - The E2 protein of the papillomavirus plays an essential role in the viral life
      cycle. Through a yeast two-hybrid screening, human polo-like kinase 1 was found
      to interact with human papillomavirus type 5 E2. Further characterization
      identified that the domains responsible for the interaction are the
      transactivation domain of HPV-5 E2 and the sequence between the kinase and the
      polo box domains of Plk1. In vivo, Plk1 and HPV-5 E2 are colocalized at the
      nuclear speckles. In the skin epithelium not infected with epidermodysplasia
      verruciformis associated HPVs, Plk1 is expressed in the stratum basale,
      indicating that the Plk1-HPV-5 E2 interaction likely occurs in the keratinocytes
      at the basal layer of the epithelium upon infection of HPV-5. Both HPV-5 E2 and
      Plk1 also interact with the E2 binding domain of Brd4. The E2 binding domain of
      Brd4 is phosphorylated by Plk1 in vitro, and this phosphorylation event is
      blocked by the presence of HPV-5 E2. Hence, these findings suggest the
      possibility that the cellular function of Brd4 is de-regulated by forming a
      complex with HPV-5 E2 in the infected epithelial cells.

PMID- 19152412
TI  - Mutations in the interferon sensitivity-determining region of hepatitis C virus
      genotype 2a correlate with response to pegylated-interferon-alpha 2a monotherapy.
AB  - The interferon sensitivity-determining region (ISDR) is thought to be inhibited
      by the double-stranded RNA-dependent protein kinase (PKR). Several studies have
      reported a relationship between the ISDR and interferon (IFN) responsiveness.
      However, this relationship is controversial. The aim of this study was to
      investigate whether genomic heterogeneity of the ISDR among patients with
      hepatitis C virus (HCV) genotype 2a affects the response to pegylated-IFN-alpha
      2a monotherapy. Eighty patients (47 men, 33 women; mean age: 54.2 +/- 12.9 years)
      infected with HCV genotype 2a were evaluated. HCV viral loads were determined by
      real-time PCR. The ISDR (amino acids 2193-2228) was examined by direct
      sequencing. Thirty-one patients received subcutaneous injections of pegylated-IFN
      alpha 2a (180 microg) once weekly for 24 weeks, and 35 patients received
      injections for 48 weeks. Fourteen patients withdrew from treatment. Of the
      remaining 66 patients, 51 (77.3%) showed a sustained virologic response. Factors
      related to sustained virologic response on multivariate analysis were rapid
      virologic response (negative HCV at 4 weeks; odds ratio: 0.033; 95% confidence
      interval (95% CI) 0.003-0.363; P = 0.0052) and the number of mutations in the
      ISDR (odds ratio: 0.025; 95% CI 0.001-0.476; P = 0.0141). There were no
      significant differences in other factors, including sex, age, aspartate
      aminotransferase, alanine aminotransferase, platelet count, duration of
      treatment, and HCV viral load. Rapid virologic response and the ISDR sequence
      variations are significantly associated with response to pegylated-IFN-alpha 2a
      monotherapy in Japanese patients with HCV genotype 2a.

PMID- 19152413
TI  - Primary human endothelial cells support direct but not antibody-dependent
      enhancement of dengue viral infection.
AB  - Microvascular plasma leakage is the hallmark of dengue hemorrhagic fever and
      dengue shock syndrome. The precise molecular mechanisms leading to microvascular
      leakage are yet to be determined, but dengue virus (DENV) infection and
      consequent endothelial cell death has been suggested as its major cause. However,
      the extent of endothelial cell permissiveness to DENV infection and the magnitude
      of cell death following DENV infection are controversial. To clarify this issue,
      we analyzed the kinetics and consequences of DENV infection of human umbilical
      vein endothelial cells (HUVEC) using a novel molecularly cloned DENV2-16681
      virus. Viral replication was detected as early as 24 hr post-infection by RT-PCR
      and plaque assays. However, merely 2% of HUVEC were DENV antigen-positive even
      after 96 hr of infection as measured by the FACS indirect immunofluorescence
      assays. Unlike monocytes/macrophages, HUVEC did not support antibody dependent
      enhancement of dengue viral infection due to a lack of FcgammaRI and FcgammaRII.
      Furthermore, DENV infection did not increase HUVEC apoptosis as compared to mock
      infected cells. Because in vitro only a small percentage of endothelial cells
      were productively infected in vitro with no significant apoptosis occurring in
      either infected or bystander cells, it would be important to re-examine whether
      direct dengue viral infection of endothelium is the major cause of the extensive
      vascular leakage observed in patients with dengue hemorrhagic fever and dengue
      shock syndrome.

PMID- 19152414
TI  - Detection of human bocavirus in respiratory, fecal, and blood samples by real
      time PCR.
AB  - Human bocavirus (HBoV) has been detected worldwide in respiratory samples. Two
      real-time PCR assays, targeting the non-structural protein (NP-1) and viral
      protein (VP-1) genes, were designed and validated to detect HBoV in patients with
      respiratory disease, gastroenteritis, or systemic illness. Sensitivity of the NP
      1 and VP-1 assays were equal to the conventional PCR assay previously described
      by Allander et al. [2005: Proc Natl Acad Sci USA 102: 12891-12896] being 100%,
      and giving specificity of 94% and 93%, respectively. There was no cross-reaction
      identified with unrelated respiratory agents, or to human DNA. The limits of
      detection were 10 copies of genomic DNA equivalents per reaction for both assays.
      The assays were used to screen three different sample populations, combined nose,
      and throat swabs (n = 96) from children with acute respiratory disease, fecal
      samples (n = 375) from adults, and children with gastroenteritis and whole blood
      (n = 229) collected from 31 immunocompromised children taken over an 18-month
      period. In total 17 (18%) respiratory samples and 18 (4.8%) fecal samples were
      identified as having HBoV present. Of the pediatric whole blood specimens
      investigated, HBoV was detected in six (2.6%) samples from four patients. In
      summary, two real-time PCR assays targeting different genes were designed and
      validated for use as screening methods for the detection of HBoV. HBoV was found
      in three different specimen types: parent-collected combined nose-throat swabs,
      fecal samples collected from symptomatic individuals and whole blood from
      immunocompromised children.

PMID- 19152415
TI  - Exceptional genetic variability of hepatitis B virus indicates that Rwanda is
      east of an emerging African genotype E/A1 divide.
AB  - In Western Africa, hepatitis B virus (HBV) genotype E predominates throughout a
      vast crescent spanning from Senegal to Namibia and at least to the Central
      African Republic to the East. Although from most of the eastern parts of sub
      Saharan Africa only limited sets of strains have been characterized, these belong
      predominantly to genotype A. To study how far the genotype E crescent extends to
      the East, a larger number of HBV strains from Rwanda were analyzed. Phylogenetic
      analysis of 45 S fragment sequences revealed strains of genotypes A (n = 30), D
      (n = 10), C (n = 4), and B (n = 1). Twelve genotype A sequences formed a new
      cluster clearly separated from the reference strains of the known sub-genotypes.
      Thus, with four genotypes and at least six sub-genotypes and a new cluster of
      genotype A strains, HBV shows an exceptional genetic variability in this small
      country, unprecedented in sub-Saharan Africa. Despite this exceptional genetic
      variability, not a single genotype E virus was found indicating that this country
      does not belong to the genotype E crescent, but is east of an emerging African
      genotype E/A1 divide.

PMID- 19152416
TI  - An improved approach to identify epidemiological and phylogenetic transmission
      pairs of source and contact tracing of hepatitis B.
AB  - The transmission of infectious diseases can be traced using epidemiological and
      molecular information. In the current study, the congruence was assessed between
      sequence data of the hepatitis B virus (HBV) and epidemiological information
      resulting from source and contact tracing of patients seen at the Municipal
      Public Health Service in Rotterdam between 2002 and 2005. HBV genotypes A-G were
      present in 62 acute and 334 chronic HBV patients. At the sequence level, the
      identical sequences of members of epidemiological transmission pairs and the
      rarity of such pairs provided strong support for correctness of the hypothesized
      transmission routes. The molecular support for epidemiological transmission pairs
      derived from source and contact tracing was further assessed by using topological
      constraints in parsimony analyses in agreement with epidemiological information,
      and by taking the presence of polymorphic sites of HBV within patients into
      account. This, in principle, allows mutations in epidemiological clusters. Of 22
      epidemiological clusters, six could be refuted, four clusters received support
      from the molecular analysis, and support for the remaining twelve clusters was
      ambiguous. Two of the four epidemiological pairs that received molecular support
      had diverged (by 3 and 15 mutations). These results show that levels of
      divergence cannot be used simply as an indicator of the likelihood that groups of
      sequences constitute transmission pairs. Instead, to confirm or refute
      transmission pairs, it is necessary to assess the likelihood of a common origin
      of HBV variants in epidemiologically defined transmission groups relative to the
      HBV diversity in the local community.

PMID- 19152417
TI  - Genetic variability of human immunodeficiency virus-1 in Bahia state, Northeast,
      Brazil: high diversity of HIV genotypes.
AB  - The HIV-1 genetic variability in Bahia state, Brazil, was investigated. DNA
      samples from 229 and 213 HIV-1-infected individuals were analyzed using the
      heteroduplex mobility assay (HMA) in gag and env fragments, respectively. One
      hundred seventy-five samples were characterized in both genes. Thirty-two subtype
      F and BF recombinant viruses were sequenced and analyzed by phylogenetic methods.
      The combination of HMA and sequencing results showed that seven different HIV-1
      genotypes comprised this sample: 147 (84%) B/B, 4 (2.3%) F/F, 3 (1.7%) B/F, 1
      (0.6%) F/B, 1 (0.6%) F/D, 1 (0.6%) BF/F, and 18 (10.3%) BF/B. A significant
      divergence was observed between these two techniques results (84.4%). This is
      explained by the low accuracy of the HMA for detecting recombinant viruses. These
      recombinants were unrelated to CRF12, while two sequences were related to CRF28
      and CRF29. Nineteen BF mosaics shared the same gag breakpoint. In conclusion, the
      use of HMA may be inappropriate in regions where different subtypes are co
      circulating. Subtype B is the most common genotype, however, an increased
      prevalence (13.1%) of different BF variants and a potentially new CRF suggest
      that recombination is occurring frequently in Bahia. These viruses were
      associated with women infected heterosexually. Finally, this study identified the
      presence of an F/D recombinant HIV-1 in Brazil.

PMID- 19152418
TI  - Evaluation of properties of chitosan as an adjuvant for inactivated influenza
      vaccines administered parenterally.
AB  - Studies on mice showed that chitosan as an adjuvant for H5 inactivated influenza
      vaccines administered intramuscularly enhances significantly antibody titers and
      protective efficiency not only against homologous influenza viruses, but also
      against drift variants. Chitosan adjuvanted vaccines induced high antibody titers
      after a single immunization and with a low dose of antigen. High antibody titers
      remained for at least 6 months. Chitosan adjuvanted vaccine stored at 4 degrees C
      preserves its adjuvant properties for at least 8 months. Chitosan stimulates
      proliferative and cytotoxic activity of splenic mononuclear leukocytes in mice
      and promotes an increase in the numbers of CD3, CD3/NK, I-AK (MHC II), and H-2Db
      (MHC I) cells. After intramuscular immunization, chitosan did not induce IgE
      antibodies and antibodies against chitosan itself. Chitosan is a promising
      adjuvant candidate for inactivated influenza vaccines administered parenterally.

PMID- 19152420
TI  - Identification of the novel KI Polyomavirus in paranasal and lung tissues.
AB  - KI is a novel polyomavirus identified in the respiratory secretions of children
      with acute respiratory symptoms. Whether this reflects a causal role of the virus
      in the human respiratory disease remains to be established. To investigate the
      presence of KIV in the respiratory tissue, we examined 20 fresh lung cancer
      specimens and surrounding normal tissue along with one paranasal and one lung
      biopsy from two transplanted children. KIV-VP1 gene was detected in 9/20 lung
      cancer patients and 2/2 transplanted patients. However, amplification of the
      sequence coding for the C-terminal part of the early region of KIV performed on
      the 11 positive cases was successful only in two malignant lung tissues, one
      surrounding normal tissue, and 1/2 biopsies tested. Phylogenetic analysis
      performed on the early region of KIV (including the four Italian isolates), BKV
      and JCV revealed the presence of three distinct clades. Within the KIV clade two
      sub-clades were observed. A sub-clade A containing the four Italian strains, and
      a sub-clade B comprising the Swedish and Australian isolates. Interestingly, the
      two Italian strains identified in normal tissue clustered together, whereas those
      detected in malignant tissue fell outside this cluster. In vitro studies are
      needed to investigate the transforming potential of KIV strains.

PMID- 19152421
TI  - Elements of morphology: standard terminology for the ear.
AB  - An international group of clinicians working in the field of dysmorphology has
      initiated the standardization of terms used to describe human morphology. The
      goals are to standardize these terms and reach consensus regarding their
      definitions. In this way, we will increase the utility of descriptions of the
      human phenotype and facilitate reliable comparisons of findings among patients.
      Discussions with other workers in dysmorphology and related fields, such as
      developmental biology and molecular genetics, will become more precise. Here we
      introduce the anatomy of the ear and define and illustrate the terms that
      describe the major characteristics of the ear.

PMID- 19152422
TI  - Elements of morphology: standard terminology for the nose and philtrum.
AB  - An international group of clinicians working in the field of dysmorphology has
      initiated the standardization of terms used to describe human morphology. The
      goals are to standardize these terms and reach consensus regarding their
      definitions. In this way, we will increase the utility of descriptions of the
      human phenotype and facilitate reliable comparisons of findings among patients.
      Discussions with other workers in dysmorphology and related fields, such as
      developmental biology and molecular genetics, will become more precise. Here we
      introduce the anatomy of the nose and philtrum, and define and illustrate the
      terms that describe the major characteristics of these body regions.

PMID- 19152419
TI  - High-risk HPV types in lesions of the uterine cervix of female commercial sex
      workers in the Philippines.
AB  - In order to prevent cervical cancer, vaccines against human papilloma virus types
      16 (HPV-16) and 18 (HPV-18) have been implemented worldwide. However, the HPV
      types that cause cancer can differ according to geographical area and ethnicity.
      In this new era of the HPV vaccine, it is important to elucidate the prevalent
      HPV types in each area. Therefore, the prevalence of HPV infection and cervical
      abnormalities among 369 female commercial sex workers in the Philippines were
      examined. HPV L1 gene was amplified by polymerase chain reaction (PCR) using
      modified GP5+/6+ primers, and genotyping was performed by sequencing cloned PCR
      products. HPV DNA was detected in 211 (57.2%) women, among whom 46 HPV types were
      identified. HPV-52 was most common and multiple-type infection was observed in
      44.5%. Among 56 women with abnormal cervical cytology (low- and high-grade
      squamous intraepithelial lesions and adenocarcinoma in situ), HPV-52 was most
      common (23.2%), followed by HPV-16 (19.6%), -58 (10.7%), and -67 (10.7%). Only
      27% of these women were positive for HPV-16 and -18. Multivariate analysis
      revealed that HPV-16, -39, -52, -67, and -82 were significantly associated with
      abnormal cytology. Repeated analysis of HPV-52 single-positive samples using the
      original GP5+/6+ PCR primers produced negative results in 57% of cases,
      suggesting that the prevalence of HPV-52 infection may have been underestimated
      in previous studies, and the current vaccines may not be sufficient for
      preventing infection and the development of premalignant lesions of the cervix in
      women in the Philippines.

PMID- 19152423
TI  - Proteomic profiling in pancreatic cancer with and without lymph node metastasis.
AB  - The aim of the study was to observe different protein profiles in pancreatic
      cancer with and without lymph node metastasis (LNM), and search for novel LNM
      associated proteins, which would help to understand the metastatic mechanisms and
      provide targets for therapeutic interventions. Cancer nests were manually
      miscrodissected from 8 LNM and 7 non-LNM pancreatic cancer tissues, and the
      protein extracts were then separated by difference gel electrophoresis (DIGE) and
      identified by MALDI-TOF-TOF. Four differently regulated proteins, ezrin, radixin,
      moesin, and c14orf166, were selected for further validation by Western blot and
      immunohistochemistry. In DIGE analysis, we identified 18 up-regulated proteins
      and 15 down-regulated proteins in LNM pancreatic cancer nests compared with non
      LNM ones. Western blot and immunohistochemical analyses confirmed that radixin,
      moesin and c14orf166, but not ezrin, had significantly higher expression levels
      in LNM pancreatic cancers than in non-LNM controls. In conclusion, the specific
      protein profiles found in this study might provide new insights into the
      mechanism of lymph node metastasis. For the first time, c14orf166 was identified
      asa novel metastasis-associated protein, and the roles of radixin, moesin and
      c14orf166 in cancer metastasis deserve further investigations.

PMID- 19152424
TI  - Efficient hepatocyte engraftment and long-term transgene expression after
      reversible portal embolization in nonhuman primates.
AB  - The feasibility of ex vivo gene therapy as an alternative to liver
      transplantation for the treatment of liver metabolic diseases needs to be
      analyzed in large animal models. This approach requires appropriate gene transfer
      vectors and effective hepatocyte engraftment. Lentiviral vectors have the ability
      to transduce nondividing differentiated cells, such as hepatocytes, and portal
      vein occlusion increases hepatocyte engraftment. We investigated whether
      reversible portal vein embolization combined with ex vivo lentivirus-mediated
      gene transfer is an effective approach for successful hepatocyte engraftment in
      nonhuman primates and whether the transgene remains expressed in the long term in
      transplanted hepatocytes in situ. Simian hepatocytes were isolated after left
      lobe resection, and the left and right anterior portal branches of animals were
      embolized with absorbable material. Isolated hepatocytes were labeled with
      Hoechst dye or transduced in suspension with lentiviruses expressing green
      fluorescent protein under the control of the human apolipoprotein A-II promoter
      and transplanted via the inferior mesenteric vein. The whole procedure was well
      tolerated. The embolized liver was revascularized within 2 weeks. The volume of
      nonembolized liver increased from 38.7% +/- 0.8% before embolization to 55.9% +/-
      1% after embolization and hepatocytes significantly proliferated (10.5% +/- 0.4%
      on day 3 after embolization). Liver repopulation after transplantation with
      Hoechst-labeled hepatocytes was 7.4% +/- 1.2%. Liver repopulation was 2.1% +/-
      0.2% with transduced hepatocytes, a proportion similar to that obtained with
      Hoechst-labeled cells, given that the mean transduction efficacy of simian
      hepatocyte population was 34%. Transgene expression persisted at 16 weeks after
      transplantation. CONCLUSION: We have developed a new approach to improve
      hepatocyte engraftment and to express a transgene in the long term in nonhuman
      primates. This strategy could be suitable for clinical applications.

PMID- 19152425
TI  - Synergism between smoking and alcohol consumption with respect to serum gamma
      glutamyltransferase.
AB  - There is increasing evidence that serum levels of the liver enzyme gamma
      glutamyltransferase (gamma-GT) are an important predictor of incidence and
      mortality of various diseases. Apart from alcohol consumption, body mass index
      and smoking have been found to be associated with serum levels, but little is
      known about potential interactions of these factors. The aim of this study was to
      assess the individual and joint impact of alcohol consumption and smoking on
      levels of gamma-GT, with particular attention to potential differences by sex.
      The study was based on data of 8465 subjects aged 50 to 74 years, obtained at
      baseline examination of the ESTHER study, a large population-based cohort study
      in Germany. Exposure-outcome relationships were assessed in women and men,
      adjusting for potential confounders by multiple regression. In both sexes,
      moderate to heavy alcohol consumption (100+ g/week) was associated with 1.7-fold
      increased odds of elevated gamma-GT (>50 IU/L) in reference to nonsmoking alcohol
      abstainers, whereas smoking by itself was unrelated to gamma-GT. However, when
      moderate to heavy alcohol consumption was present in combination with heavy
      smoking, the odds ratios (95% CI) increased to 2.9 (1.1-7.6) in women and to 3.8
      (2.2-6.6) in men (test for interaction between alcohol consumption and smoking:
      P(females) = 0.12, P(males) = 0.0017). CONCLUSION: Our results support the notion
      of a detrimental interaction between cigarette smoking and alcohol consumption as
      determinants of elevated serum gamma-GT, especially in men.

PMID- 19152426
TI  - Reassessing selection criteria prior to liver transplantation for hepatocellular
      carcinoma utilizing the Scientific Registry of Transplant Recipients database.
AB  - The current model of liver graft allocation in place in the United States favors
      transplantation of patients with small hepatocellular carcinomas (HCCs) within
      the Milan criteria (a single tumor up to 5 cm in diameter or up to three lesions,
      none larger than 3 cm). Although several reports have suggested that these
      criteria could be extended, there is currently no agreement on new selection
      tools. In this study, we performed an overview of 6478 adult recipients of an
      isolated first liver transplant registered in the Scientific Registry of
      Transplant Recipients (SRTR) database. From March 2002 to January 2008,
      increasing numbers of patients outside Milan criteria (P <or= 0.001) have been
      registered for a transplant, but they still represent less than 5% of the
      transplants performed for HCC. Of all the tested variables (tumor number, largest
      tumor size, and Milan and University of California San Francisco criteria), only
      total tumor volume (TTV; P <or= 0.05) and alpha fetoprotein (AFP; P <or= 0.001)
      could predict patient survival. While these two parameters demonstrated
      independent behaviors (no patient demonstrated an increase in both values), a
      composite score was defined, with patients with a TTV > 115 cm(3) or an AFP > 400
      ng/mL being outside criteria. The combined TTV/AFP score efficiently predicted
      posttransplant survival (hazard ratio = 2, 95% confidence interval = 1.7-2.4, P
      <or= 0.001); patients not meeting these criteria had a survival below 50% at 3
      years. CONCLUSION: According to the present SRTR data, Milan criteria are too
      restrictive, and patients with larger TTV can enjoy satisfactory posttransplant
      survivals. A composite patient selection score combining TTV and AFP was the most
      effective of all tested staging criteria for the prediction of posttransplant
      patient survival for candidates with HCC.

PMID- 19152428
TI  - Two novel CYP21A2 missense mutations in Italian patients with 21-hydroxylase
      deficiency: Identification and functional characterisation.
AB  - Steroid 21-hydroxylase deficiency is present in more than 90% of patients with
      congenital adrenal hyperplasia (CAH), an inherited metabolic disorder of adrenal
      steroidogenesis. Impaired enzymatic activity leads to the accumulation of
      metabolic intermediates (progesterone and 17-hydroxyprogesterone), which results
      in excessive androgen production and varied signs of virilisation. CYP21A2 is an
      active gene and encodes for the steroid 21-hydroxylase enzyme, whereas CYP21A1P
      is an inactive pseudogene that contains a series of deleterious mutations. The
      major part of disease- causing mutations in CYP21A2 alleles are CYP21A1P-derived
      sequence transferred to the active gene by macro or microconversion events. Only
      around 5% of all disease-causing CYP21A2 alleles harbour rare mutations that do
      not originate from the pseudogene. In this report, we report the characterisation
      of two novel CYP21A2 missense mutations (p.H119R and p.I194N) found in two
      unrelated Italian patients with nonclassic (NC) CAH clinical diagnosis.
      Functional in vitro assays for mutagenized CYP21 enzymes were performed in
      transiently transfected mammalian cells to test the residual enzyme activity and
      the apparent kinetic values. The residual activities obtained for p.H119R and
      p.I194N mutants allowed to classify them as NC-CAH associated mutations. These
      results correlate with the rate of severity of the patients' disease. Finally,
      the new p.H119R and p.I194N mutations should be included in the panel of those
      already listed for association with the NC form of 21-hydroxylase deficiency.

PMID- 19152427
TI  - Is the iron donor lipocalin 2 implicated in the pathophysiology of hereditary
      hemochromatosis?
AB  - Under normal conditions, iron is taken up by the cells through the transferrin
      mediated pathway. However, in hereditary hemochromatosis, a common iron
      overloading disorder associated with mutations in the HFE gene, iron in plasma
      exceeds transferrin-binding capacity, and non-transferrin-bound iron (NTBI)
      appears in the circulation of patients with iron overload. NTBI can be taken up
      by hepatocytes through a transferrin-independent pathway. Lipocalin 2 (Lcn2), a
      secreted protein of the lipocalin family, has emerged as the mediator of an
      alternative, transferrin-independent pathway for cellular iron delivery. To
      evaluate the importance of Lcn2 in the pathogenesis of hepatic iron loading in
      Hfe knockout mice, we generated HfeLcn2 double-deficient mice. Our studies
      revealed that deletion of Lcn2 in Hfe-knockout mice does not influence hepatic
      iron accumulation in Hfe(-/-) mice, or their response to iron loading, as the
      phenotype of HfeLcn2(-/-) mice remained indistinguishable from that of Hfe(-/-)
      mice. CONCLUSION: Lcn2 is not essential for iron delivery to hepatocytes in
      hemochromatosis.

PMID- 19152429
TI  - An assessment of erythroid response to epoetin alpha as a single agent versus in
      combination with granulocyte- or granulocyte-macrophage-colony-stimulating factor
      in myelodysplastic syndromes using a meta-analysis approach.
AB  - BACKGROUND: Epoetin alpha (EPO) continues to be the initial treatment of choice
      for most anemic patients with myelodysplastic syndromes (MDS). Over the years,
      different therapeutic strategies have been adopted to optimize the clinical
      benefits of EPO in this setting. METHODS: In the current meta-analysis of
      published literature, erythroid response (ER) rates with EPO as a single agent
      versus its combination with granulocyte-colony-stimulating factor (G-CSF) or
      granulocyte-macrophage-colony-stimulating factor (GM-CSF) were compared. RESULTS:
      The assessment indicated that the ER rates were comparable between the 2 EPO
      based therapeutic strategies. Furthermore, EPO monotherapy at a higher dose of
      60,000 to 80,000 U weekly produced significantly higher ER rates (64.5%) compared
      with the standard oncology dose of 30,000 to 40,000 U weekly either as a single
      agent (49%; P < .001) or in combination with G-CSF/GM-CSF (50.6% P = .007). In
      addition, when transfusion-dependent patients were assessed separately, both EPO
      monotherapy and its combination with G-CSF/GM-CSF produced comparable and
      appreciable levels of transfusion independence (28.8% and 24.8%, respectively).
      CONCLUSIONS: In the current meta-analysis, higher doses of EPO demonstrated
      better ER rates compared with EPO at standard doses alone or in combination with
      G-CSF/GM-CSF. Furthermore, the authors concluded that prospective clinical
      studies are warranted to evaluate the use of higher doses of EPO in anemic
      patients with MDS.

PMID- 19152430
TI  - Breast biopsy patterns and outcomes in Surveillance, Epidemiology, and End
      Results-Medicare data.
AB  - BACKGROUND: Despite known benefits to needle biopsy for suspicious breast
      lesions, variability in the use of this technique has been documented in
      practice. We sought to study the use of needle biopsy and open surgical biopsy in
      women with breast cancer, predictors of needle biopsy use, and the effect of
      biopsy choice on overall number of surgical procedures needed to treat breast
      cancer. METHODS: We analyzed Surveillance, Epidemiology, and End Results (SEER)
      Medicare data for 45,542 women diagnosed between 1991 and 1999 with ductal
      carcinoma in situ and stage I-II breast cancer. By using diagnosis and procedure
      codes from 3 months before to 6 months after the SEER diagnosis, we classified
      the initial biopsy as needle or surgical. By using multivariate logistic
      regression, we identified patient and tumor characteristics associated with
      needle biopsy use, and estimated the association between initial biopsy type and
      likelihood for multiple breast surgeries. RESULTS: Needle biopsy was the initial
      procedure for 11,073 (24.3%) women. In multivariate analyses, needle biopsy use
      varied significantly by race, year of diagnosis, and tumor size. After
      controlling for patient and tumor characteristics, needle biopsy use was
      associated with a reduced likelihood of multiple breast surgeries (odds ratio,
      0.35; 95% confidence interval, 0.34-0.37). CONCLUSIONS: Use of needle biopsy as
      the initial breast cancer procedure was more common among black women and those
      with larger tumors, and increased significantly over time. Providers should
      consider needle biopsy when clinically feasible as the initial breast procedure,
      because it may reduce the number of surgeries needed to treat breast cancer.

PMID- 19152431
TI  - Comparison of American Joint Committee on Cancer pathologic stage T3a versus T3b
      urothelial carcinoma: analysis of patient outcomes.
AB  - BACKGROUND: The radical cystectomy experience at Vanderbilt University Medical
      Center was scrutinized to determine whether there was a difference in survival
      between patients with lymph node-negative pathologic T3a versus pathologic T3b
      urothelial carcinoma of the bladder. METHODS: Pathologic and clinical data were
      reviewed on patients who underwent radical cystectomy for urothelial carcinoma
      between 1995 and 2005. We excluded patients with nontransitional cell cancer,
      lymph node disease, or with unknown lymph node status. Of the 790 reviewed
      patients, 75 patients (9.4%) were diagnosed with pathologic T3 urothelial cancer
      of the bladder. The impact of pathologic substaging (pT3a vs pT3b) was examined
      to determine the effect on overall, disease-specific, and recurrence-free
      survival. RESULTS: The mean age was 68.6 years (36 years to 83 years). Median
      overall follow-up was 25.3 months (1.13 months to 130.17 months). Median follow
      up for patients alive at last follow-up was 55.9 months (25.3 months to 130.2
      months). Actuarial overall survival at 5 years was 29.5% for pT3a and 29.3% for
      pT3b (P = .79). Actuarial disease-specific survival at 5 years was 54.1% for pT3a
      and 42.4% for pT3b (P = .21). Actuarial recurrence-free survival at 5 years was
      68.1% for pT3a and 71.9% for pT3b (P = .53). CONCLUSIONS: There were no
      significant differences in overall, disease-specific, or recurrence-free survival
      when comparing lymph node-negative pT3a versus pT3b urothelial cancer of the
      bladder following radical cystectomy. Simplification of pathologic staging for
      urothelial carcinoma of the bladder should be considered at future revisions of
      the American Joint Committee on Cancer staging system.

PMID- 19152432
TI  - Preoperative assessment enables the early detection and successful treatment of
      lymphedema.

PMID- 19152434
TI  - Understanding bladder cancer death: tumor biology versus physician practice.
AB  - BACKGROUND: To the authors' knowledge, the extent to which death from bladder
      cancer is attributable to tumor biology or physician practice patterns is
      unknown. For this reason, the relative importance of broadening indications for
      aggressive therapy has unclear implications. METHODS: Patients whose deaths were
      caused directly by bladder cancer were identified using institutional (n = 126
      patients) and administrative (n = 6326 patients) data sources. By using implicit
      review (clinical data, 2001-2005) and explicit algorithms (Surveillance,
      Epidemiology, and End Results [SEER]-Medicare, 1992-2002), the authors estimated
      the proportion of potentially avoidable deaths from bladder cancer. RESULTS:
      After an implicit review of clinical data, 40 of 126 deaths (31.7%) were
      classified as potentially avoidable. Compared with those patients who were deemed
      unsalvageable, these patients generally presented with nonmuscle-invasive disease
      (80% vs 25.6%; P < .001), received multiple courses of intravesical therapy
      (32.5% vs 1.2%; P < .001), and had a more protracted course from diagnosis to
      aggressive treatment (median, 23 months vs 2 months; P < .001). An explicit
      review of claims data indicated that between 31.6% and 46.8% of the 6326 bladder
      cancer deaths identified in the SEER-Medicare data potentially were avoidable,
      depending on the survivorship threshold chosen. Patients whose deaths potentially
      were avoidable more commonly presented with nonmuscle-invasive disease (66.7% vs
      24.7%; P < .0001) and lower grade disease (35.1% vs 15.1%; P < .0001).
      CONCLUSIONS: The greatest inroads into reducing death from bladder cancer likely
      hinge on earlier detection or improvement of systemic therapies. However,
      changing physician practice may translate into nontrivial reductions in bladder
      cancer mortality.

PMID- 19152435
TI  - A novel algorithm to improve pathologic stage prediction of clinically organ
      confined muscle-invasive bladder cancer.
AB  - BACKGROUND: An algorithm was created to predict pathologic stage in patients with
      clinically organ-confined muscle-invasive bladder cancer. METHODS: The sample
      consisted of 133 consecutive patients scheduled to undergo cystectomy. To develop
      a tool to predict nonorgan-confined disease before surgery, principal component
      analysis (PCA) was applied. Patients were stratified into a training set (n = 89)
      and a validation set (n = 44), and 7 parameters were evaluated: levels of
      carcinoembryonic antigen, cancer antigen (CA) 125, and carbohydrate antigen (CA)
      19-9; clinical stage; presence of hydronephrosis; presence of carcinoma in situ;
      and initial tumor size >3 cm. PCA was applied to the training set to determine
      the weight of each parameter. A PCA score was generated for each patient in the
      set, and a cutoff defining nonorgan-confined disease was established. The
      accuracy of the cutoff was quantified by the area under the receiver operator
      characteristics curve (AUC). The model was then applied to the validation set
      without recalculation; the AUC and the positive and negative predictive values of
      the validation set were calculated. RESULTS: On pathologic evaluation, 71
      patients (53%) were found to have organ-confined tumors and 62 patients (47%) had
      extravesical disease. The AUC was 0.85 in the training group (95% confidence
      interval [95% CI], 0.71-0.97) and 0.84 in the validation group (95% CI, 0.75
      0.93). The positive and negative predictive values in the validation group were
      88% (95% CI, 71%-96%) and 94% (95% CI, 71%-99%), respectively. CONCLUSIONS: The
      newly devised, internally validated, algorithm was 85% accurate in predicting
      nonorgan-confined bladder disease before cystectomy. Further external validation
      in a large cohort was recommended as still necessary.

PMID- 19152436
TI  - Iron supplementation and erythropoiesis-stimulatory agents in the treatment of
      cancer anemia.
AB  - Unresponsiveness to erythropoiesis-stimulatory agents (ESA), which occurs in 30%
      to 50% of patients, is a major limitation to the treatment of chemotherapy
      related anemia (CRA). This may be related in part to the dysregulation of iron
      metabolism, leading to functional iron deficiency. However, the use of iron
      supplementation during treatment with ESA has not been pursued as rigorously in
      anemic patients with cancer as it has in patients with chronic kidney disease. In
      this article, the authors discuss the role of iron supplementation in the setting
      of CRA in view of recent reports that have addressed this issue.

PMID- 19152437
TI  - The hair follicle barrier to involvement by malignant melanoma.
AB  - BACKGROUND: Melanoma characteristically grows within the epidermis along the
      dermal-epidermal junction, sometimes extending outward up to several centimeters
      beyond the foci of invasive tumors. Although follicular involvement by malignant
      melanoma is widely recognized, to the authors' knowledge no previously published
      data address this phenomenon. METHODS: To examine the growth characteristics of
      in situ melanomas in relation to the hair follicle microanatomy, the authors
      analyzed 100 cases of primary cutaneous melanomas (61 in situ and 39 invasive
      melanomas with significant in situ components) obtained from pathology clinical
      archives. RESULTS: Eighty-two (82%) cases of melanoma in situ demonstrated tumor
      cells within >or=1 hair follicles. Of those, 57 (69.5%) cases demonstrated the
      tumor cells only within the infundibulum. Extension of the tumor cells down to
      the isthmus was observed in 24 cases (29.3%). In only 1 exceptional case (1%)
      were tumor cells detected beneath the level of the hair follicle bulge.
      CONCLUSIONS: The authors postulate that a physiologic barrier restricts the
      intraepithelial spread of melanoma tumor cells at or beyond the level of the stem
      cell niche in the hair follicle bulge. Although the nature of this barrier
      remains to be elucidated, the distinct biologic characteristics of the hair
      follicle bulge may provide clues to understanding this phenomenon.

PMID- 19152438
TI  - Time to prostate-specific antigen nadir independently predicts overall survival
      in patients who have metastatic hormone-sensitive prostate cancer treated with
      androgen-deprivation therapy.
AB  - BACKGROUND: The objective of this study was to evaluate the relation between the
      kinetics of prostate-specific antigen (PSA) decline after the initiation of
      androgen-deprivation therapy (ADT) and overall survival (OS) in men with
      metastatic, hormone-sensitive prostate cancer (HSPC). METHODS: The authors'
      institutional database was used to identify a cohort of men with metastatic HSPC
      who were treated with ADT. Patients were included if they had at least 2 serum
      PSA determinations before PSA nadir and at least 1 serum PSA value available
      within 1 month of ADT initiation. Patient characteristics, PSA at ADT initiation,
      nadir PSA, time to PSA nadir (TTN), and PSA decline (PSAD) in relation to OS were
      analyzed. RESULTS: One hundred seventy-nine patients were identified, and they
      had a median follow-up after ADT initiation of 4 years. The median OS after ADT
      initiation was 7 years. The median PSA level at ADT initiation and PSA nadir were
      47 ng/mL and 0.28 ng/mL, respectively. On univariate analysis: TTN <6 months,
      PSAD >52 ng/mL per year, PSA nadir >or=0.2 ng/mL, PSA >or=47.2 ng/mL at ADT
      initiation, and Gleason score >7 were associated with shorter OS. On multivariate
      analysis, TTN <6 months, Gleason score >7, and PSA nadir >or=0.2 ng/mL
      independently predicted shorter OS. CONCLUSIONS: To the authors' knowledge, this
      was the first report to demonstrate that a faster time to reach a PSA nadir after
      the initiation of ADT was associated with shorter survival duration in men with
      metastatic HSPC. These results need confirmation but may indicate that a rapid
      initial response to ADT indicates more aggressive disease.

PMID- 19152439
TI  - Reducing bladder cancer deaths: the preemptive cystectomy approach.

PMID- 19152440
TI  - Factors associated with local and distant recurrence and survival in patients
      with resected nonsmall cell lung cancer.
AB  - BACKGROUND: This study assessed the impact of surgical, histopathologic and
      patient-related factors on the risks of local and distant recurrence and overall
      survival for patients with stages I through IIIA nonsmall cell lung carcinoma
      (NSCLC) undergoing definitive resection with or without adjuvant chemotherapy.
      METHODS: This study included 373 consecutive patients treated between 2000 and
      2005 who did not receive adjuvant or neoadjuvant radiotherapy, had at least 3
      months of follow-up, and did not have a history of other cancers within 5 years
      of the diagnosis of their NSCLC. Of these, 52% had pathologic stage IA disease,
      30% had stage IB, 5% had stage IIA, 8% had stage IIB and 5% had stage III
      disease. Forty-four patients received chemotherapy. RESULTS: The median follow-up
      was 33 months. Local failure rates at 2 years, 3 years, and 5 years were 16%,
      22%, and 32%, respectively; distant recurrence rates were 13%, 15%, and 21%,
      respectively. Multivariable analysis revealed that local recurrence was
      significantly associated with the presence of lymphatic or vascular invasion
      (LVI), the use of chemotherapy, and having diabetes; distant recurrence was
      significantly higher in patients with nonsquamous cell histology, those
      undergoing pneumonectomy, and those with more advanced TNM stage. Survival was
      significantly associated with age, history of myocardial infarction, performance
      of a pneumonectomy, histology, LVI, and the number of positive N1 lymph nodes.
      CONCLUSIONS: Local recurrence was the predominant type of failure in this series.
      Patient with diabetes or LVI may benefit from close surveillance and aggressive
      therapy of asymptomatic local recurrences, especially when chemotherapy is given
      in addition to surgery.

PMID- 19152441
TI  - High prevalence of BRAF mutation in a Brazilian cohort of patients with sporadic
      papillary thyroid carcinomas: correlation with more aggressive phenotype and
      decreased expression of iodide-metabolizing genes.
AB  - BACKGROUND: Although several studies undoubtedly demonstrated that BRAF mutation
      is an important genetic event in the pathogenesis of papillary thyroid carcinoma
      (PTC), its prognostic significance and correlation with less differentiated
      states remains unclear. It has been suggested that the discrepancy may be at
      least partially due to the insufficient number of cases analyzed, epidemiologic
      factors, and a combination of different variants of PTC included in these
      studies. METHODS: In this context, the prevalence of the BRAF mutation in a
      Brazilian cohort of PTCs (n = 120) was first assessed and correlated with
      clinicopathologic features. The BRAF exon 15 mutation was evaluated by direct
      sequencing. Furthermore, using quantitative polymerase chain reaction, the issue
      of whether the expression level of the iodide-metabolizing genes (NIS and TSHR)
      was correlated with BRAF mutational status was investigated. RESULTS: A high
      prevalence of the BRAF mutation was found in PTC cases (48%). The BRAF mutation
      was found to be significantly associated with the classic variant of PTC (66%; P
      < .0001), although it was found in the follicular variant as well (21%). Subtype
      stratification demonstrated that the BRAF V600E mutation was associated with
      tumor size, extrathyroid invasion, the presence of lymph node metastasis and risk
      of disease recurrence, and mortality in patients with the classic variant of PTC.
      Moreover, the expression levels of NIS and TSHR were remarkably lower in PTCs
      harboring the BRAF V600E mutation. CONCLUSIONS: These findings provide further
      evidence that BRAF might be associated with a more aggressive phenotype and less
      differentiated state due to decreased expression of iodide-metabolizing genes.
      The search for a BRAF mutation in the current study population appears to be
      valuable for predicting prognosis and guiding management in patients with PTC.

PMID- 19152443
TI  - Intussusception of the bowel in adults: a review.
AB  - Intussusception of the bowel is defined as the telescoping of a proximal segment
      of the gastrointestinal tract within the lumen of the adjacent segment. This
      condition is frequent in children and presents with the classic triad of cramping
      abdominal pain, bloody diarrhea and a palpable tender mass. However, bowel
      intussusception in adults is considered a rare condition, accounting for 5% of
      all cases of intussusceptions and almost 1%-5% of bowel obstruction. Eight to
      twenty percent of cases are idiopathic, without a lead point lesion. Secondary
      intussusception is caused by organic lesions, such as inflammatory bowel disease,
      postoperative adhesions, Meckel's diverticulum, benign and malignant lesions,
      metastatic neoplasms or even iatrogenically, due to the presence of intestinal
      tubes, jejunostomy feeding tubes or after gastric surgery. Computed tomography is
      the most sensitive diagnostic modality and can distinguish between
      intussusceptions with and without a lead point. Surgery is the definitive
      treatment of adult intussusceptions. Formal bowel resection with oncological
      principles is followed for every case where a malignancy is suspected. Reduction
      of the intussuscepted bowel is considered safe for benign lesions in order to
      limit the extent of resection or to avoid the short bowel syndrome in certain
      circumstances.

PMID- 19152442
TI  - Intestinal hormones and growth factors: effects on the small intestine.
AB  - There are various hormones and growth factors which may modify the intestinal
      absorption of nutrients, and which might thereby be useful in a therapeutic
      setting, such as in persons with short bowel syndrome. In part I, we focus first
      on insulin-like growth factors, epidermal and transferring growth factors,
      thyroid hormones and glucocorticosteroids. Part II will detail the effects of
      glucagon-like peptide (GLP)-2 on intestinal absorption and adaptation, and the
      potential for an additive effect of GLP2 plus steroids.

PMID- 19152444
TI  - Midkine translocated to nucleoli and involved in carcinogenesis.
AB  - Midkine (MK) is a heparin-binding growth factor with its gene first identified in
      embryonal carcinoma cells at early stages of retinoic acid-induced
      differentiation. MK is frequently and highly expressed in a variety of human
      carcinomas. Furthermore, the blood MK level is frequently elevated with advance
      of human carcinomas, decreased after surgical removal of the tumors. Thus, it is
      expected to become a promising marker for evaluating the progress of carcinomas.
      There is mounting evidence that MK plays a significant role in carcinogenesis
      related activities, such as proliferation, migration, anti-apoptosis,
      mitogenesis, transforming, and angiogenesis. In addition, siRNA and anti-sense
      oligonucleotides for MK have yielded great effects in anti-tumor activities.
      Therefore, MK appears to be a potential candidate molecular target of therapy for
      human carcinomas. In this paper, we review MK targeting at nucleoli in different
      tumor cells and its role in carcinogenesis to deepen our understanding of the
      mechanism of MK involved in carcinogenesis.

PMID- 19152445
TI  - Mycobacterium avium subspecies paratuberculosis and its relationship with Crohn's
      disease.
AB  - The hypothesis postulating that Mycobacterium avium paratuberculosis (MAP) is the
      cause of Crohn's disease (CD) has been circulating for many years. Advances in
      molecular techniques, such as polymerase chain reaction and culture methods, have
      enabled researchers to demonstrate that there is an association between MAP and
      CD. Recently, genome-wide association studies have identified novel
      susceptibility genes for CD, which are critical for generation of an adaptive
      immune response that is protective against intracellular pathogens, including M.
      tuberculosis infection. However, the role of MAP as a cause of CD suffered a
      setback with the report that administration of antimycobacterial therapy failed
      to lead to a sustained response in CD patients. Accordingly, this review sought
      neither to confirm nor refute this, but instead to survey recent literature on
      the role of MAP in CD.

PMID- 19152446
TI  - DNA-guided hepatitis B treatment, viral load is essential, but not sufficient.
AB  - Hepatitis B virus (HBV) infection is a global public health problem that concerns
      350 million people worldwide. Individuals with chronic hepatitis B (CHB) are at
      increased risk of developing liver cirrhosis, hepatic de-compensation and
      hepatocellular carcinoma. To maintain undetectable viral load reduces chronic
      infection complications. There is no treatment that eradicates HBV infection.
      Current drugs are expensive, are associated with adverse events, and are of
      limited efficacy. Current guidelines try to standardize the clinical practice.
      Nevertheless, controversy remains about management of asymptomatic patients with
      CHB who are hepatitis B e antigen (HBeAg)-positive with normal alanine
      aminotransferase, and what is the cut-off value of viral load to distinguish
      HBeAg-negative CHB patients and inactive carriers. We discuss in detail why DNA
      level alone is not sufficient to begin treatment of CHB.

PMID- 19152447
TI  - Reversal of multi-drug resistance by pSUPER-shRNA-mdr1 in vivo and in vitro.
AB  - AIM: To explore the possibility of reversing multi-drug resistance (MDR) to
      HepG2/mdr1 in vitro and in vivo with RNA interference (RNAi). METHODS: HepG2/mdr1
      was obtained by cloning the whole gene mdr1 into HepG2 cells. shRNA targeting
      sequence was designed to be homologous to the P-gp encoding MDR1 mRNA consensus
      sequence. pSUPER-shRNA/mdr1 was constructed using the enzyme-digested technique.
      HepG2/mdr1 cells were transfected with vectors of pSUPER-shRNA/mdr1 to measure
      their efficacy by real-time PCR for mdr1 mRNA, flow cytometry (FCM) for P-gp
      expression, and Rhodamine efflux, MTT method for HepG2/mdr1 function,
      respectively. In vivo, mice tumors were treated by injecting pSUPER-shRNA/mdr1 in
      situ and into intra-abdominal cavity. Tumors were collected to create cell
      suspension and cryosections after chemotherapy with adriamycin and mytomycin. The
      cell suspension was incubated in RPMI-1640 supplemented with G418 to screen
      stable cells for appreciating the reversal of MDR. Cryosections were treated with
      immunohistochemistry technique to show the effectiveness of transfection and the
      expression of P-gp. RESULTS: pSUPER-shRNA/mdr1 was successfully constructed,
      which was confirmed by sequencing. The MDR phenotype of HepG2/mdr1 was decreased
      significantly in vitro transfection. HepG2/mdr1 showing its MDR was reversed
      notably in P-gp expression (11.0% vs 98.2%, P<0.01). Real-time PCR showed that
      mRNA/mdr1 was lower in test groups than in control groups (18.73+/-1.33 vs
      68.03+/-2.21, P<0.001). Compared with HepG2, the sensitivity of HepG2/mdr1 and
      HepG2/mdr1-dsRNA cells to ADM was decreased by 1.64 times and 15.6 times,
      respectively. The accumulation of DNR in positive groups was decreased evidently.
      In vivo, the p-gp expression in positive groups was significantly lower than that
      in control groups (65.1% vs 94.1%, P<0.05). The tumor suppressing rate in test
      groups was 57.8%. After chemotherapy, the growth rate in test groups was lower
      than that in control groups (700.14+/-35.61 vs 1659.70+/-152.54, P<0.05). Similar
      results were also observed under fluorescence microscope, and confirmed by Image
      Pro Plus 4.5 analysis. CONCLUSION: pSUPER-shRNA/mdr1 vector system allows simple,
      stable and durable nonviral knockdown of P-gp by RNAi in malignant cells and
      animals to restore their sensitivity to adriamycin.

PMID- 19152448
TI  - Suppression of pancreatic carcinoma growth by activating peroxisome proliferator
      activated receptor gamma involves angiogenesis inhibition.
AB  - AIM: To study the possible actions and mechanisms of peroxisome proliferator
      activated receptor gamma (PPARgamma), a ligand-activated transcription factor, in
      pancreatic carcinogenesis, especially in angiogenesis. METHODS: Expressions of
      PPARgamma and retinoid acid receptor (RXRalpha) were examined by reverse
      transcription polymerase chain reaction (RT-PCR) with immunocytochemical
      staining. Pancreatic carcinoma cells, PANC-1, were treated either with 9-cis-RA,
      a ligand of RXRalpha, or with 15-deoxy-Delta(12,14) prostaglandin J(2) (15d
      PGJ(2)), a ligand of PPARgamma, or both. Antiproliferative effect was evaluated
      by cell viability using methyltetrazolium (MTT) assay. A pancreatic carcinoma
      xenograft tumor model of nude mice was established by inoculating PANC-1 cells
      subcutaneously. Rosiglitazone, a specific ligand of PPARgamma, was administered
      via water drinking in experimental group of nude mice. After 75 d, all mice were
      sacrificed. Expression of proliferating cell nuclear antigen (PCNA) in tumor
      tissue was examined with immunohistochemical staining. Expression of vascular
      endothelial growth factor (VEGF) mRNA in PANC-1 cells, which were treated with
      15d-PGJ(2) or 9-cis-RA at various concentrations or different duration, was
      detected by semi-quantitative RT-PCR. Effects of Rosiglitazone on changes of
      microvascular density (MVD) and VEGF expression were investigated in xenograft
      tumor tissue. Neovasculature was detected with immunohistochemistry staining
      labeled with anti-IV collagen antibody, and indicated by MVD. RESULTS: RT-PCR and
      immunocytochemical staining showed that PPARgamma and RXRalpha were expressed in
      PANC-1 cells at both transcription level and translation level. MTT assay
      demonstrated that 15d-PGJ(2), 9-cis-RA and their combination inhibited the growth
      of PANC-1 cells in a dose-dependent manner. 9-cis-RA had a combined inhibiting
      action with 15d-PGJ(2) on the growth of pancreatic carcinoma. In vivo studies
      revealed that Rosiglitazone significantly suppressed the growth of pancreatic
      carcinoma as compared to control group (0.48+/-0.23 cm(3) vs 2.488+/-0.59 cm(3),
      P<0.05), and the growth inhibition rate was 80.7%. Immunohistochemistry study
      showed that PCNA was down regulated in Rosiglitazone-treated group compared to
      the control group. 15d-PGJ(2), 9-cis-RA and their combination inhibited the
      expression of VEGF mRNA in PANC-1 cells in a dose- and time-dependent manner. MVD
      was decreased more significantly in Rosiglitazone-treated mice (10.67+/-3.07)
      than in the control group (31.44+/-6.06) (P<0.01). VEGF expression in xenograft
      tumor tissue was also markedly down-regulated in Rosiglitazone-treated mice.
      CONCLUSION: Activation of PPARgamma inhibits the growth of pancreatic carcinoma
      both in vitro and in vivo. Suppression of tumor angiogenesis by down-regulating
      the expression of VEGF may be one of the mechanisms by which PPARgamma activation
      inhibits the growth of pancreatic carcinoma.

PMID- 19152449
TI  - Capecitabine and irinotecan with and without bevacizumab for advanced colorectal
      cancer patients.
AB  - AIM: To investigate the efficacy and safety of cape-citabine plus irinotecan +/-
      bevacizumab in advanced or metastatic colorectal cancer patients. METHODS: Forty
      six patients with previously untreated, locally-advanced or metastatic colorectal
      cancer (mCRC) were recruited between 2001-2006 in a prospective open-label phase
      II trial, in German community-based outpatient clinics. Patients received a
      standard capecitabine plus irinotecan (CAPIRI) or CAPIRI plus bevacizumab (CAPIRI
      BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in
      cases of > grade 2 toxicity. The treatment choice of bevacizumab was at the
      discretion of the physician. The primary endpoints were response and toxicity and
      secondary endpoints included progression-free survival and overall survival.
      RESULTS: In the CAPIRI group vs the CAPRI-Bev group there were more female than
      male patients (47% vs 24%), and more patients had colon as the primary tumor site
      (58.8% vs 48.2%) with fewer patients having sigmoid colon as primary tumor site
      (5.9% vs 20.7%). Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev: 82%
      vs 58.6%. Partial response rates were 29.4% and 34.5%, and tumor control rates
      were 70.6% and 75.9%, respectively. No complete responses were observed. The
      median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI
      Bev, respectively. The median overall survival for CAPIRI was 15 mo (458 d) and
      for CAPIRI-Bev 24 mo (733 d). These differences were not statistically different.
      In the CAPIRI-Bev, group, two patients underwent a full secondary tumor resection
      after treatment, whereas in the CAPIRI group no cases underwent this procedure.
      CONCLUSION: Both regimens were well tolerated and offered effective tumor growth
      control in this outpatient setting. Severe gastrointestinal toxicities and
      thromboembolic events were rare and if observed were never fatal.

PMID- 19152450
TI  - Risk factors for colonic diverticular bleeding: a Westernized community based
      hospital study.
AB  - AIM: To evaluate the risk factors-other than nonsteroidal anti-inflammatory drugs
      for colonic diverticular bleeding in a westernized population. METHODS: One
      hundred and forty patients, treated for symptomatic diverticular disease in a
      community based hospital, were included. Thirty (21%) had signs of diverticular
      bleeding. Age, gender, and the results of colonoscopy were collected and compared
      to a group of patients with nonbleeding symptomatic diverticulosis. Records were
      reviewed for comorbidities, such as obesity, alcohol consumption, smoking habits
      and metabolic diseases. Special emphasis was put on arterial hypertension,
      cardiovascular events, diabetes mellitus, hyperuricemia and hypercholesterinemia.
      RESULTS: There was no difference between patients with diverticular hemorrhage
      and those with nonbleeding symptomatic diverticulosis regarding gender ratio
      (male/female 9/21 vs 47/63) and diverticular localisation. Bleeding patients
      differed in respect to age (73.4+/-9.9 vs 67. 8+/-13.0, P<0.013). Significant
      differences were found between both groups regarding the presence of
      hyperuricemia and use of steroids and nonsteroidal anti-inflammatory drugs.
      Patients with three concomitant metabolic diseases were also identified as being
      at risk of bleeding. A forward stepwise logistic regression analysis revealed
      steroids, hyperuricemia and the use of calcium-channel blockers as independent
      risk factors of bleeding. CONCLUSION: Beside nonsteroidal anti-inflammatory
      steroid drug use, antihypertensive medication and concomitant arteriosclerotic
      diseases are risk factors for colonic diverticular hemorrhage. Our results
      support the hypothesis of an altered arteriosclerotic vessel as the source of
      bleeding.

PMID- 19152451
TI  - Clinical expression of insulin resistance in hepatitis C and B virus-related
      chronic hepatitis: differences and similarities.
AB  - AIM: To investigate the prevalence of the clinical parameters of insulin
      resistance and diabetes in patients affected by chronic hepatitis C (CHC) or
      chronic hepatitis B (CHB). METHODS: We retrospectively evaluated 852 consecutive
      patients (726 CHC and 126 CHB) who had undergone liver biopsy. We recorded age,
      sex, ALT, type 2 diabetes and/or metabolic syndrome (MS), body mass index (BMI),
      and apparent disease duration (ADD). RESULTS: Age, ADD, BMI, prevalence of MS and
      diabetes in patients with mild/moderate liver fibrosis were significantly higher
      in CHC. However, the degree of steatosis and liver fibrosis evaluated in liver
      biopsies did not differ between CHC and CHB patients. At multivariate analysis,
      age, sex, BMI, ALT and diabetes were independent risk factors for liver fibrosis
      in CHC, whereas only age was related to liver fibrosis in CHB. We also evaluated
      the association between significant steatosis (>30%) and age, sex, BMI, diabetes,
      MS and liver fibrosis. Diabetes, BMI and liver fibrosis were associated with
      steatosis >30% in CHC, whereas only age and BMI were related to steatosis in CHB.
      CONCLUSION: These data may indicate that hepatitis C virus infection is a risk
      factor for insulin resistance.

PMID- 19152452
TI  - Effect of preoperative immunonutrition and other nutrition models on cellular
      immune parameters.
AB  - AIM: To evaluate the effects of preoperative immunonutrition and other nutrition
      models on the cellular immunity parameters of patients with gastrointestinal
      tumors before surgical intervention. In addition, effects on postoperative
      complications were examined. METHODS: Patients with gastrointestinal tumors were
      randomized into 3 groups. The immunonutrition group received a combination of
      arginine, fatty acids and nucleotides. The second and third group received normal
      nutrition and standard enteral nutrition, respectively. Nutrition protocols were
      administered for 7 d prior to the operation. Nutritional parameters, in
      particular prealbumin levels and lymphocyte subpopulations (CD4+, CD8+,
      CD16+/56+, and CD69 cells) were evaluated before and after the nutrition
      protocols. Groups were compared in terms of postoperative complications and
      duration of hospital stay. RESULTS: Of the 42 patients who completed the study,
      16 received immunonutrition, 13 received normal nutrition and 13 received
      standard enteral nutrition. prealbumin values were low in every group, but this
      parameter was improved after the nutritional protocol only in the immunonutrition
      group (13.64+/-8.83 vs 15.98+/-8.66, P=0.037). Groups were similar in terms of
      CD4+, CD16+/56, and CD69+ prior to the nutritional protocol; whereas CD8+ was
      higher in the standard nutrition group compared to the immunonutrition group.
      After nutritional protocols, none of the groups had an increase in their
      lymphocyte subpopulations. Also, groups did not differ in terms of postoperative
      complications and postoperative durations of hospital stay. CONCLUSION:
      Preoperative immunonutrition provided a significant increase in prealbumin
      levels, while it did not significantly alter T lymphocyte subpopulation counts,
      the rate of postoperative complications and the duration of hospital stay.

PMID- 19152453
TI  - Nonalcoholic fatty liver disease in asymptomatic Brazilian adolescents.
AB  - AIM: To evaluate the prevalence and clinical characteristics of Nonalcoholic
      fatty liver disease (NAFLD) among asymptomatic Brazilian adolescents. METHODS:
      Transversal observational study included asymptomatic adolescents with central
      obesity from private and public schools in Salvador-Bahia, northeastern Brazil.
      The children answered a questionnaire that included age, gender, race, and
      medical history, and were submitted to a complete physical exam and abdominal
      ultrasound. Biochemical exams included: ALT, AST, GGT, C reactive protein (CRP),
      fasting glucose, insulin, cholesterol and triglycerides. Criteria for NAFLD
      included: the presence of steatosis in ultrasound and/or high level of ALT,
      negative or occasional historic of intake of alcohol (<or= 140 g/wk), negative
      investigation for hepatitis A, B, C, auto-immune hepatitis, Wilson disease and
      hemochromatosis. RESULTS: From October, 2005 to October, 2006, the study included
      1801 subjects between 11 and 18 years of age and a mean age of 13.7+/-2.0 years.
      One hundred ninety-nine had central obesity. The prevalence of NAFLD was 2.3%,
      most of whom were male and white. Insulin resistance (IR) was observed in 22.9%
      of them and had positive correlations with ALT and GGT (P<0.05). Elevated CRP was
      observed in 6.9% of the cases; however, it was not associated with WC, IR or
      liver enzymes. CONCLUSION: The prevalence of NAFLD in Brazilian adolescents was
      low. The ethnicity may have influence this frequency in the population studied,
      which had a large proportion of African descendents.

PMID- 19152454
TI  - Analysis of the histologic features in the differential diagnosis of intrahepatic
      neonatal cholestasis.
AB  - AIM: To compare the histologic features of the liver in intrahepatic neonatal
      cholestasis (IHNC) with infectious, genetic-endocrine-metabolic, and idiopathic
      etiologies. METHODS: Liver biopsies from 86 infants with IHNC were evaluated. The
      inclusion criteria consisted of jaundice beginning at 3 mo of age and a hepatic
      biopsy during the 1st year of life. The following histologic features were
      evaluated: cholestasis, eosinophilia, giant cells, erythropoiesis, siderosis,
      portal fibrosis, and the presence of a septum. RESULTS: Based on the diagnosis,
      patients were classified into three groups: group 1 (infectious; n=18), group 2
      (genetic-endocrine-metabolic; n=18), and group 3 (idiopathic; n=50). There were
      no significant differences with respect to the following variables: cholestasis,
      eosinophilia, giant cells, siderosis, portal fibrosis, and presence of a septum.
      A significant difference was observed with respect to erythropoiesis, which was
      more severe in group 1 (Fisher's exact test, P=0.016). CONCLUSION: A significant
      difference was observed in IHNC of infectious etiology, in which erythropoiesis
      was more severe than that in genetic-endocrine-metabolic and idiopathic
      etiologies, whereas there were no significant differences among cholestasis,
      eosinophilia, giant cells, siderosis, portal fibrosis, and the presence of a
      septum.

PMID- 19152455
TI  - Application of stool-PCR test for diagnosis of Helicobacter pylori infection in
      children.
AB  - AIM: To evaluate the usefulness of stool-PCR test for diagnosis of Helicobacter
      pylori (H pylori) infection in pediatric populations. METHODS: Based on
      endoscopic features (including nodular gastritis, erosive duodenitis and ulcer)
      and/or a positive rapid urease test (RUT) obtained during endoscopy, 28 children
      from a group of children admitted to the Children's Medical Center of Tehran for
      persistent upper gastrointestinal problems were selected to compare biopsy-based
      tests with stool-PCR. Their gastric activity and bacterial density were graded by
      the updated Sydney system, and their first stool after endoscopy was stored at 
      70 degrees C. Biopsies were cultured on modified campy-blood agar plates and
      identified by gram-staining, biochemical tests, and PCR. Two methods of phenol
      chloroform and boiling were used for DNA extraction from H pylori isolates.
      Isolation of DNA from stool was performed using a stool DNA extraction kit
      (Bioneer Inc, Korea). PCR was performed using primers for detection of vacA,
      cagA, and 16srRNA genes in both isolates and stool. RESULTS: Sixteen out of 28
      child patients (57%) were classified as H pylori positive by biopsy-based tests,
      of which 11 (39%) were also positive by stool-PCR. Sensitivity and specificity of
      stool-PCR was 62.5% and 92.3% respectively. H pylori was observed in histological
      sections for 10 out of 11 stool-positive patients. Association was observed
      between higher score of H pylori in histology and positivity of stool-PCR. Also
      association was observed between the more severe form of gastritis and a positive
      stool-PCR. CONCLUSION: Association between higher score of H pylori in histology
      and a positive stool-PCR make it a very useful test for detection of H pylori
      active infection in children. We also suggest that a simple stool-PCR method can
      be a useful test for detection of H pylori virulence genes in stool.

PMID- 19152456
TI  - Endoscopic features predictive of gastric cancer in superficial lesions with
      biopsy-proven high grade intraepithelial neoplasia.
AB  - AIM: To investigate the macroscopic and clinico-pathologic features of gastric
      cancer in patients with biopsy-suggested high grade intraepithelial neoplasia.
      METHODS: Patients with biopsy-confirmed gastric high grade intraepithelial
      neoplasia were reviewed from January 2001 to March 2008. Pathologic sections were
      re-evaluated by two senior pathologists. Patients with an en-bloc resection of
      the lesion within two months after the diagnosis of high grade intraepithelial
      neoplasia were enrolled in the study. Clinical manifestations, endoscopic
      features, biopsy and surgical pathology of all patients were collected and
      analyzed. The data acquired were subjected to univariate and multivariate
      analysis. RESULTS: Seventy-two superficial gastric lesions with a pathologic
      diagnosis of high grade intraepithelial neoplasia based on biopsy specimens were
      enrolled. True high grade intraepithelial neoplasia was finally proved in 16
      lesions and gastric cancer in the rest 56 lesions, most of which (96.4%) were
      differentiated carcinomas. The result of univariate analysis indicated that the
      size and the presence of marked ulcer plaque or scar in a superficial lesion were
      independently associated with gastric cancer (P<0.05), when high grade
      intraepithelial neoplasia was diagnosed by biopsy pathology. The results of
      multivariate analysis revealed the size greater than 1.5 cm [odds ratio (OR)
      18.400, P<0.001] and the presence of 5-odd mm ulcer plaque or scar (OR 10.000,
      P=0.044) were associated with gastric cancer. Accordingly, the sensitivity,
      specificity and negative predictive value of multivariate analysis for predicting
      "true high grade intraepithelial neoplasia" was 87.5%, 89.3% and 96.2%,
      respectively. CONCLUSION: Macroscopic findings are of value in differentiation
      between high grade intraepithelial neoplasia and superficial gastric cancer. This
      may simplify patient work-up and save costs for patients and healthcare system.

PMID- 19152457
TI  - Fast track clinical pathway implications in esophagogastrectomy.
AB  - AIM: To investigate the feasibility of fast track clinical pathway for esophageal
      tumor resections. METHODS: One hundred and fourteen patients with esophageal
      carcinoma who underwent esophagogastrectomy from January 2006 to October 2007 in
      our department were studied. Fast track clinical pathway included analgesia
      control, fluid infusion volume control, early ambulation and enteral nutrition.
      Nasogastric tube was removed 3 d after operation and chest tube was removed 4 d
      after operation as a routine, and full liquid diet 5 d after operation. RESULTS:
      Among 114 patients (84 men and 30 women), 26 patients underwent fast track
      surgery, including 17 patients over 65 years old and 9 under 65 (P=0.014); 18
      patients who had preoperative complications could not bear fast track surgery
      (P<0.001). No significant differences in tolerance of fast track surgery were
      attributed to differences in gender, differentiated degree or stage of tumor,
      pathological type of tumor, or operative incision. The median length of hospital
      stay was 7 d (5-28 d), 4% patients were readmitted to hospital within 30 d of
      discharge. Three patients died and postoperative mortality was 2.6%. All 3
      patients had no determinacy to fast track surgery approach. CONCLUSION: The
      majority of patients with esophageal carcinoma can tolerate fast track surgery.
      Patients younger than 65 or who have no preoperative diseases have the best
      results. Median length of hospital stay has been reduced to 7 d.

PMID- 19152458
TI  - Postpartum spontaneous colonic perforation due to antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) is a multi-systemic disease being
      characterized by the presence of antiphospholipid antibodies that involves both
      arterial and venous systems resulting in arterial or venous thrombosis, fetal
      loss, thrombocytopenia, leg ulcers, livedo reticularis, chorea, and migraine. We
      document a previously unreported case of a 37-year-old female in whom APS was
      first manifested by infarction and cecal perforation following cesarean section.
      At laparotomy the underlying cause of colonic perforation was not clear and after
      resection of the affected bowel an ileo-colostomy was performed. The diagnosis of
      APS was established during post-operative hospital stay and the patient was
      commenced on warfarin. Eventually, she made a full recovery and had her stoma
      reversed after 4 mo. Pregnancy poses an increased risk of complications in women
      with APS and requires a more aggressive approach to the obstetric care. This
      should include full anticoagulation in the puerperium and frequent doppler
      ultrasound monitoring of uterine and umbilical arteries to detect complications
      such as pre-eclampsia and placental insufficiency.

PMID- 19152459
TI  - nm23H1 expression and its role in the evolution of non-gastrointestinal
      malignancies.
AB  - The role of nm23H1 genetic instability is not limited to gastrointestinal
      malignancies. A similar close relationship exists between nm23H1 genetic
      instability and other non gastrointestinal systemic malignancies. For instance,
      in oral malignant melanomas with lymphoid metastasis, the nm23H1 expression is
      significantly lower in contrast to tumors with no lymphoid metastasis. Similarly,
      increased metastasis is seen in non small cell lung cancers following down
      regulation of nm23H1 in conjunction with KAI-1 down regulation. There is an
      inverse relationship between tumor stage and metastasis and nm23H1 expression in
      individuals with prostate carcinomas and a similar relationship exists between
      microsatellite instability of the nm23H1 gene and ovarian carcinogenesis. For
      instance, nearly 70.5% of stage I-II ovarian tumors express nm23H1 in sharp
      contrast to only 25% of stage III-IV ovarian tumors. As is clearly evident,
      nm23H1 has a major role in gastrointestinal and non-gastrointestinal
      carcinogenesis. The coming few years will hopefully see the development of new
      strategies by virtue of which we can alter nm23H1 expression and thus decrease
      the risk of metastasis in malignant tumors.

PMID- 19152460
TI  - [Progress in diagnostic tests for osteoporoses].

PMID- 19152461
TI  - [Genetic diagnosis of pheochromocytoma].

PMID- 19152462
TI  - [Evidence based nursing in long-term care].

PMID- 19152463
TI  - [Clinical and diagnostic findings in rheumatism].

PMID- 19152464
TI  - [Clinical research and internal medicine specialists].

PMID- 19152465
TI  - [Evaluation of reasoning in clinical medicine].

PMID- 19152466
TI  - Testing the stability of the polyethylene acetabulum cemented on a frozen bone
      graft substrate on a model of an artificial hip joint.
AB  - The stability of the polyethylene acetabulum cemented on a substrate made of
      frozen bone grafts was investigated. The force was applied to the edge of the
      acetabulum and the magnitude of the force and resulting displacement were
      recorded. These tests were preceded by stress testing, during which the
      acetabulum was subjected to loading forces of 1 or 3 kN through 100,000 cycles.
      Additionally the influence of the thickness of grafts layer on the overall
      stability of an implant was also determined. The experiments proved that such
      factors as initial compacting of bone grafts, magnitude of the loading force and
      thickness of grafts layer greatly affect the stability of the artificial
      acetabulum.

PMID- 19152467
TI  - Durability evaluation of a friction couple intended for implantological
      stabilization of complete dentures.
AB  - The paper presents the results of the study of the titanium implant-elastomeric
      membrane attachment, conducted from the point of view of potential utilization of
      the results in forecasting the durability of retention elements representing a
      new solution of dentures based on implants. The examination was carried out using
      a device designed by the author, which allowed the simulation of the process of
      inserting and removing dentures. Titanium counter specimens, simulating implants,
      were subjected to surface modification through their sandblasting with 350 um and
      500 um abrasives, so as to diversify their roughness. The elastomeric membranes
      constituting a retention element of the attachment were made of a silicone
      material, Molloplast B. The influence of the number of cycles (one cycle meaning
      one insertion and removal of a denture) on the attachment's retention force was
      studied. In order to better reflect the natural conditions, the device was
      equipped with a chamber which made it possible to perform the examination in an
      artificial saliva environment. The study has shown that the application of the
      polymer material Molloplast B for constructing the new type retention elements of
      dentures based on implants ensures practically constant values of the
      attachment's retention force in the required 6-month utilization period. After
      the time of denture usage, being eight times longer than originally assumed, the
      loss of retention force does not exceed 43% in any of the attachments
      investigated and the retention force values still allow the attachments to
      operate, although their effectiveness is partly reduced.

PMID- 19152468
TI  - Influence of tongue activity on lower complete denture retention under biting
      forces.
AB  - Tongue activity constitutes a helpful factor in using complete dentures. It has
      not however been identified, to what extent the force of the tongue can directly
      stabilize the denture during the occurrence of biting forces. Dislodgement force
      of the denture held by the patients tongue shows a significant dependence on the
      tongue strength efficiency, however only few patients are able to analyze the
      mechanisms of using their tongues to stabilize the denture. The results of the
      FEM analysis show that the tongue has a strong advantageous influence on denture
      lateral stability during chewing and also during biting, and a slightly lower
      ability of counteracting the denture destabilization towards the front. The role
      played by the tongue in denture retention is not only that it locates the denture
      by means of tactile sensation but also that it supports the forces counteracting
      denture dislodgement.

PMID- 19152469
TI  - Assessment of biomechanical risk at work: practical approaches and tools.
AB  - The paper illustrates some methods and tools supporting work-related risk
      assessment with reference to ergonomics and biomechanics, in particular. These
      aspects will also be described through the analysis of two case studies in order
      to highlight the main characteristics and problems found during the application
      phase. Furthermore, using modelling and simulation software, the utility and
      reliability of such tools in support of the work-related risk assessment will
      also be evaluated.

PMID- 19152470
TI  - Strength of proximal humeral fraction fixation employing implants of various
      types--a study of porcine bones.
AB  - In this study, the authors assess the strength of proximal humerus fracture
      fixation using different methods. The strength, while pulling out the chosen
      single Kirschner wires implanted in porcine bone, has been examined. Tests
      concerning the strength of fixation with different types of implants have been
      carried out on prepared models. We observed the maximum strength of the bone
      single wire coupling for Kirschner wires of a 2.5 mm diameter with 100 mm thread
      where mean was 2396 N (SD 345). The mean strength of the 4 wires fracture
      fixation for Kirschner wires of a 2.5 mm diameter with 100 mm thread was 736 N
      (SD 229) and was similar to Kirschner wires of a 2.5 mm diameter with 10 mm
      thread where mean was 709 N (SD 191).

PMID- 19152471
TI  - Moments of muscular strength of knee joint extensors and flexors during
      physiotherapeutic procedures following anterior cruciate ligament reconstruction
      in males.
AB  - The objective of this paper was to evaluate maximal muscular strength moments of
      knee joint extensors and flexors in males subjected to physiotherapeutic
      procedures. 120 males were selected for the study. The first group consisted of
      54 patients who underwent a 6 month physiotherapy programme following anterior
      cruciate ligament (ACL) reconstruction. The control group comprised 54 males
      without knee joint injuries. The measurement of muscular strength moments was
      performed in healthy and affected knee joint flexor and extensor muscles
      postoperatively, during the 13th and 21st week of physiotherapy. The patients'
      results were next compared with the results obtained in the control group. During
      the 13th week of physiotherapy, the values of postoperative maximal strength
      moments in knee joints were significantly lower compared to the results obtained
      in non-operated limbs and in the control group. The introduction of individual
      loads adjusted to the course of ACL graft reconstruction and fixation in the bone
      tunnel resulted in the improvement of maximal muscle strength values in the
      patients' knee joints from 13 to 21 weeks postoperatively. During the 21st week
      of physiotherapy, the values of the muscular strengths in the operated limbs were
      similar to those obtained in non-operated limbs of the patients and in the
      control group.

PMID- 19152472
TI  - Usefulness of spectroscopy for biomedical engineering.
AB  - Modifications of phenylalanine amino acid after its exposure to near-infrared
      (NIR) radiation have been investigated using ATRFTIR (Attenuated Total
      Reflectance-Fourier Transform Infrared Spectroscopy). The process of amino acid
      aggregation after its exposure to NIR has been observed. A possible mechanism of
      amino acid dimer formation has been proposed with the help of theoretical
      calculations of quantum mechanics (MP2 and B3LYP/6-31 G* level) using the
      GAUSSIAN 03 package. The usefulness of spectroscopy for biomedical engineering is
      discussed. ATR-FTIR appears to be a powerful tool for measuring tissue damage in
      aqueous environments.

PMID- 19152473
TI  - Contribution of plantar pressure to the prevention and quantification of the
      muscle-skeletal injury risk in hiking trails--a pilot study.
AB  - Hiking trails have been growing in popularity in the health and well-being
      promotion. Consequently, the foot became an object of study in order to
      understand the discomfort and pain in the lower limb. The aims of the work were:
      1) to detect tendencies for behaviour of maximum values of plantar pressure
      (MaxP) during the walk on different slopes, 2) to contribute to the methodology
      of the difficulty level of hiking trails. Equations show strong tendencies (R2 >
      0.8) of behaviour of MaxP in the lateral zones of the heel, 4th and 5th
      metatarsus as well as in the plantar zone of the hallux. The analysis of the
      difficulty level of the hiking trails branches deserves a separate presentation,
      including the technical difficulty analysis (with a compulsory emphasis on the
      biomechanics) and information on the caloric consumption and on the slopes of
      each branch.

PMID- 19152474
TI  - Microscopic and histological analysis of the processes occurring in the aperture
      and wall of a coronary vessel after stent implantation.
AB  - The serious problem of angioplasty is restenosis, which relates to approx. 15-30%
      of all the patients subjected to the procedure. The present research was inspired
      by an attempt to explain this phenomenon and to analyse its causes. Two coronary
      arteries coming from the patients after stent implantation were subjected to
      analysis using light and electron microscopy. As a result of expansion of the
      stent and pressing the implant metallic structure into the artery wall, it comes
      to breaking the endothelium continuity, uncovering the structures of the
      intercellular matrix and the internal membrane and, consequently, to creation of
      a thrombus in the damaged area. As a result of the tissue response, the
      extracellular matrix is created and neointime formed.

PMID- 19152475
TI  - Computer modelling of ciliary motility.
AB  - This article is devoted to mathematical modelling of motility of a single cilium.
      After some simplifications, a mechanical model of a cilium as well as a
      mathematical model of the mechanism of ciliary motility were proposed. These
      models are based on the hypothesis which was formulated earlier.

PMID- 19152476
TI  - Biomechanical changes of hip joint following different types of corrective
      osteotomy--photoelastic studies.
AB  - The paper presents the results of some comparative experimental studies that show
      the biomechanical changes which appear following different types of corrective
      osteotomy. The photoelastic technique was applied to plane models. The
      modifications in the stress distribution on the contour after the osteotomy in
      comparison with the situation before surgery were studied. Three types of
      osteotomy are considered: valgus osteotomy, varus osteotomy and Chiari pelvis
      osteotomy. Using the same experimental technique, the distribution of the contact
      pressure at the interface between the polyethylene cup and the femoral head is
      investigated, for a total hip prosthesis, as the extreme solution in the case of
      advanced hip arthroses. Both a normal situation and the malposition of prosthetic
      components were analyzed.

PMID- 19152477
TI  - Clinical applications of urinary organic acids. Part 2. Dysbiosis markers.
AB  - Part 1 of this series focused on urinary organic acids as markers of
      detoxification; part 2 focuses on dysbiosis markers. Intestinal microbial growth
      is accompanied by the release of products of their metabolism that may be
      absorbed and excreted in urine. Several organic acids are known to be specific
      products of bacterial metabolic action on dietary polyphenols or unassimilated
      amino acids or carbohydrates. Associated gastrointestinal or neurological
      symptoms may result from irritation of the intestinal mucosa or systemic
      distribution of absorbed neurotoxic products. Detection of abnormally elevated
      levels of these products is a useful diagnostic tool for patients with
      gastrointestinal or toxicological symptoms. Test profiles of urinary organic
      acids associated with microbial overgrowth can include benzoate, hippurate,
      phenylacetate, phenylpropionate, cresol, hydroxybenzoate, hydroxyphenylacetate,
      hydroxyphenylpropionate and 3,4-dihydroxyphenylpropionate, indican,
      tricarballylate, D-lactate, and D-arabinitol. Effective treatments for the
      associated microbial overgrowths may be directed at reducing microbial
      populations, introducing favorable microbes, and restoring intestinal mucosal
      integrity.

PMID- 19152478
TI  - The role of enzyme supplementation in digestive disorders.
AB  - This article reviews various forms of enzyme supplementation used clinically in
      digestive and absorption disorders. Enzyme supplementation plays an integral role
      in the management of various digestive disorders, particularly with regard to
      exocrine pancreatic insufficiency. However, application of enzymes may also be
      beneficial for other conditions associated with poor digestion including lactose
      intolerance. Historically, porcine and bovine pancreatic enzymes have been the
      preferred form of supplementation for exocrine pancreatic insufficiency. Use of
      microbe-derived lipase has shown promise with studies indicating benefit similar
      to pancreatic enzymes, but at a lower dosage concentration and with a broader pH
      range. Safety and efficacy of enzymes derived from microbial species in the
      treatment of conditions such as malabsorption and lactose intolerance is
      promising. Plant-based enzymes, such as bromelain from pineapple, serve as
      effective digestive aids in the breakdown of proteins. Synergistic effects have
      been observed using a combination of animal-based enzymes and microbe-derived
      enzymes or bromelain.

PMID- 19152479
TI  - Inulin-type prebiotics--a review: part 1.
AB  - This article is part 1 of a two-part review of inulin-type prebiotics. Prebiotics
      are a category of nutritional compounds grouped together by the ability to
      promote the growth of specific beneficial (probiotic) gut bacteria. Inulin-type
      prebiotics contain fructans of the inulin-type. Fructans are a category of
      nutritional compounds that encompasses naturally occurring plant oligo- and
      polysaccharides in which one or more fructosyl-fructose linkages comprise the
      majority of glycosidic bonds. To be inulin-type a fructan must have beta (2(1)
      fructosyl-fructose glycosidic bonds, which gives inulin its unique structural and
      physiological properties, allowing it to resist enzymatic hydrolysis by human
      salivary and small intestinal digestive enzymes. Inulin-type prebiotics include
      fructooligosaccharides (FOS), oligofructose, and inulin - terms that have been
      used inconsistently in both the scientific literature and in food applications.
      Commercially available inulin-type prebiotics can be extracted from food
      (typically chicory root) or synthesized from a more fundamental molecule
      (typically sucrose). Depending on the starting source and degree of processing,
      inulin-type prebiotics can be produced with very different chemical compositions.
      Some inulin-type prebiotics are relatively high in free sugars (the
      monosaccharides fructose and glucose and the disaccharide sucrose), while others
      have most or all free sugars removed. Processing can also result in mixes
      consisting exclusively of inulin-type oligosaccharides, polysaccharides, or both.
      Because inulin, oligofructose, and FOS resist enzymatic digestion in the upper
      gastrointestinal tract, they reach the colon virtually intact where they undergo
      bacterial fermentation. All inulin-type prebiotics are bifidogenic - stimulating
      the growth of Bifidobacteria species. The effects they have on other gut
      organisms are less consistent. A minimal dose of inulin-type prebiotic appears to
      be needed to produce a bifidogenic effect. However, intra-individual response to
      an identical dose of the same inulin-type prebiotic, in terms of stimulation of
      total number of Bifidobacteria and individual Bifidobacteria species, can be
      variable. Research on therapeutic uses of inulin-type prebiotics will be covered
      in part 2 of this review.

PMID- 19152480
TI  - Additive activity of royal jelly and honey against Pseudomonas aeruginosa.
AB  - As natural products garner attention in the medical field, the emergence of
      antibiotic-resistant strains of bacteria has confounded the current use of
      antibiotic therapy, leading to the re-examination of earlier remedies such as
      honey and royal jelly (RJ). Four varieties of honey and one variety of freshly
      reaped RJ were used to evaluate the additive antimicrobial action against
      Pseudomonas aeruginosa (ATCC 27853). Initially, honey and RJ were used separately
      to determine their minimum inhibitory concentration (MIC) against the tested
      strain. Next, sub-MIC concentrations of honey and RJ were incorporated into media
      to determine the minimum additive inhibitory concentration. When tested
      separately, the MIC of the four varieties of honey ranged from 12-18 percent
      (volume/volume; v/v), and that of RJ was 4 percent (v/v). When combined with RJ,
      each honey variety tested showed a greater than 90-percent drop in MIC using 3
      percent (v/v) RJ, a 66.6-percent drop in MIC using 2-percent (v/v) RJ, and a 50
      percent MIC drop with 1-percent (v/v) RJ. The MIC of RJ dropped by 75 percent
      when used with the half concentration of honey that alone provides the MIC and by
      50 percent when used with one-third the concentration of honey that alone
      provides the MIC. A strong linear correlation exists between the MIC drop of each
      variety of honey and RJ. With increasing interest in the use of alternative
      therapies and as the development of antibiotic-resistant bacteria spreads, honey
      and RJ may receive renewed recognition as wound healers.

PMID- 19152481
TI  - Riboflavin. Monograph.

PMID- 19152482
TI  - Whey protein. Monograph.

PMID- 19152486
TI  - Directional gravity sensing in gravitropism.
AB  - Plants can reorient their growth direction by sensing organ tilt relative to the
      direction of gravity. With respect to gravity sensing in gravitropism, the
      classic starch statolith hypothesis, i.e., that starch-accumulating amyloplast
      movement along the gravity vector within gravity-sensing cells (statocytes) is
      the probable trigger of subsequent intracellular signaling, is widely accepted.
      Several lines of experimental evidence have demonstrated that starch is important
      but not essential for gravity sensing and have suggested that it is reasonable to
      regard plastids (containers of starch) as statoliths. Although the word statolith
      means sedimented stone, actual amyloplasts are not static but instead possess
      dynamic movement. Recent studies combining genetic and cell biological
      approaches, using Arabidopsis thaliana, have demonstrated that amyloplast
      movement is an intricate process involving vacuolar membrane structures and the
      actin cytoskeleton. This review covers current knowledge regarding gravity
      sensing, particularly gravity susception, and the factors modulating the function
      of amyloplasts for sensing the directional change of gravity. Specific emphasis
      is made on the remarkable differences in the cytological properties,
      developmental origins, tissue locations, and response of statocytes between root
      and shoot systems. Such an approach reveals a common theme in directional gravity
      sensing mechanisms in these two disparate organs.

PMID- 19152489
TI  - Metabolomics for functional genomics, systems biology, and biotechnology.
AB  - Metabolomics now plays a significant role in fundamental plant biology and
      applied biotechnology. Plants collectively produce a huge array of chemicals, far
      more than are produced by most other organisms; hence, metabolomics is of great
      importance in plant biology. Although substantial improvements have been made in
      the field of metabolomics, the uniform annotation of metabolite signals in
      databases and informatics through international standardization efforts remains a
      challenge, as does the development of new fields such as fluxome analysis and
      single cell analysis. The principle of transcript and metabolite cooccurrence,
      particularly transcriptome coexpression network analysis, is a powerful tool for
      decoding the function of genes in Arabidopsis thaliana. This strategy can now be
      used for the identification of genes involved in specific pathways in crops and
      medicinal plants. Metabolomics has gained importance in biotechnology
      applications, as exemplified by quantitative loci analysis, prediction of food
      quality, and evaluation of genetically modified crops. Systems biology driven by
      metabolome data will aid in deciphering the secrets of plant cell systems and
      their application to biotechnology.

PMID- 19152496
TI  - Anxiety disorders during childhood and adolescence: origins and treatment.
AB  - The present review summarizes our current knowledge of the development and
      management of anxiety in children and adolescents. Consideration is given to
      limitations of this knowledge and directions for future research. The review
      begins with coverage of the development and demographic correlates of anxiety in
      young people and then moves to systematic discussion of some of the key
      etiological factors, including genetics, temperament, parenting, and individual
      experiences. The second part of the review describes current treatment strategies
      and efficacy as well as factors thought to influence treatment outcome, including
      treatment features, child factors, and parent factors. The review concludes with
      brief coverage of some more recent developments in treatment including
      alternative models of delivery and prevention strategies.

PMID- 19152500
TI  - Effect of removing the amino-terminal hexapeptide of tropomyosin on the
      properties of the thin filament.
AB  - The role of the amino-terminal region of alpha-striated muscle tropomyosin has
      been analyzed by reconstituting thin filaments with a version of the protein
      lacking the first six amino acids. While Omp T-digested tropomyosin (residues 7
      284) does not bind significantly to F-actin at micromolar concentrations, an
      interaction is induced by skeletal troponin. At a moderate ionic strength (50 mM
      KCl), the apparent Kd values are 0.26 microM (with EGTA) and 1.6 microM (with
      Ca2+). At higher neutral salt (140 mM KCl), reconstitution is observed in the
      micromolar range only at high pCa (Kd = 1.3 microM). However, when chloride is
      replaced by acetate, the binding isotherms reach saturation under both extremes
      of Ca2+ [apparent Kd values of 0.32 microM (with EGTA) and 2.6 microM (with
      Ca2+)]. The induction of binding of truncated tropomyosin to F-actin by troponin
      is attributable, in part, to troponin-I, but whereas the amino-terminal fragment
      of troponin-T (N-Tn-T, residues 1-158) enhances the effect of troponin-I in the
      case of other tropomyosin products specifically, unacetylated tropomyosin
      (residues 1-284), and carboxypeptidase-digested tropomyosin (residues 1-273)
      [Heeley, D. H., et al. (1987) J. Biol. Chem. 262, 9971-9978], it is ineffective
      with regard to Omp T-digested tropomyosin, suggesting that cleavage has disrupted
      a binding site for this section of troponin-T. Thin filaments (with Ca2+)
      containing Omp T-digested tropomyosin activate the steady-state myosin-MgATPase
      to a greater extent than the integral system, consistent with the interaction
      between N-Tn-T and the amino-terminal region of tropomyosin having a regulatory
      function. At high pCa, the truncated system exhibits a less cooperative
      interaction with myosin-S1-ADP but the affinity for the ligand is stronger. In
      context with the current methodologies, the consequences of shortening
      tropomyosin at one end as opposed to the other are the reverse of each other.

PMID- 19152501
TI  - Pink1 forms a multiprotein complex with Miro and Milton, linking Pink1 function
      to mitochondrial trafficking.
AB  - Recessive mutations in Pink1 lead to a selective degeneration of dopaminergic
      neurons in the substantia nigra that is characteristic of Parkinson disease.
      Pink1 is a kinase that is targeted in part to mitochondria, and loss of Pink1
      function can alter mitochondrial morphology and dynamics, thus supporting a link
      between mitochondrial dysfunction and Parkinson disease etiology. Here, we report
      the unbiased identification and confirmation of a mitochondrial multiprotein
      complex that contains Pink1, the atypical GTPase Miro, and the adaptor protein
      Milton. Our screen also identified an interaction between Pink1 and Mitofilin.
      Based on previously established functions for Miro and Milton in the trafficking
      of mitochondria along microtubules, we postulate here a role for Pink1 in
      mitochondrial trafficking. Using subcellular fractionation, we show that the
      overexpression of Miro and Milton, both of which are known to reside at the outer
      mitochondrial membrane, increases the mitochondrial Pink1 pool, suggesting a
      function of Pink1 at the outer membrane. Further, we document that Pink1
      expressed without a mitochondrial targeting sequence can still be targeted to a
      mitochondria-enriched subcellular fraction via Miro and Milton. The latter
      finding is important for the interpretation of a previously reported protective
      effect of Pink1 expressed without a mitochondrial targeting sequence. Finally, we
      find that Miro and Milton expression suppresses altered mitochondrial morphology
      induced by loss of Pink1 function in cell culture. Our findings suggest that
      Pink1 functions in the trafficking of mitochondria in cells.

PMID- 19152503
TI  - Efficiently enhancing regioselective acylation of 5-azacytidine catalysed by
      Candida antarctica lipase B with co-solvent mixtures as the reaction media.
AB  - A comparative study of regioselective acylation of 5-azacytidine catalysed by CAL
      B (Candida antarctica lipase B) in co-solvent mixtures and in pure organic
      solvents was performed, to our knowledge for the first time, and it was shown
      that a remarkable enhancement in the initial rate and substrate conversion in the
      reaction could be achieved with co-solvents as the reaction medium instead of
      pure organic solvents. For the CAL-B-catalysed regioselective synthesis of 5'-O
      butyryl-5-azacytidine in co-solvent mixtures, the optimal conditions were as
      follows: optimal co-solvent mixture, hexane/pyridine (40/60, v/v); initial aw
      (water activity), 0.07; enzyme dosage, 50 units/ml; vinyl butyrate/5-azacytidine
      molar ratio, 15:1; temperature, 60  degrees C. Under the optimal conditions, v0
      (the initial reaction rate), C (the substrate conversion) and the
      regioselectivity of the reaction were 0.75 mM/min, 99.0% and above 99%
      respectively. Similar phenomena were observed in the CAL-B-catalysed
      regioselective acylation of 5-azacytidine with an extensive range of fatty acid
      vinyl esters (from C2 to C18). Compared with pure pyridine, the reactions were
      greatly accelerated in a hexane/pyridine (40/60, v/v) co-solvent mixture and 5
      azacytidine could be biotransformed into its derivative 5'-O-acyl-5-azacytidine
      at a much higher conversion rate (91.4-99.0% as against 40.2-43.5%). Meanwhile,
      adoption of a co-solvent mixture as the reaction medium could also greatly lower
      the enzyme dosage and the molar ratio of acyl donor to 5-azacytidine. 

PMID- 19152505
TI  - The function of ROCO proteins in health and disease.
AB  - The ROCO family of multidomain proteins extends across the eukaryotes, and has
      been implicated in numerous cellular processes. Following the description of
      mutations causing PD (Parkinson's disease) in a human representative of the ROCO
      family, LRRK2 (leucine-rich repeat kinase 2), a great deal of research has been
      carried out into these proteins. This review examines the published data
      regarding the roles the ROCO proteins are thought to play in cell processes, and
      how the structure and domain organization of these proteins relates to their
      function.

PMID- 19152504
TI  - The ribonome: a dominant force in co-ordinating gene expression.
AB  - The ribonome is the total cellular complement of RNAs and their regulatory
      factors functioning dynamically in time and space within ribonucleoprotein
      complexes. We theorize that the ribonome is an ancient central co-ordinator that
      has evolved to communicate on multiple levels to the proteome on the one hand
      (feed-forward), and the transcriptome and RNA processing machinery on the other
      (feed-back). Furthermore, the ribonome can potentially communicate to other cells
      horizontally with implications for biological information transfer and for the
      evolution of both RNA and DNA operating systems. The post-transcriptional RNA
      operon theory of co-regulated gene expression accounts for the co-ordinated
      dynamics of RNA-binding proteins within the cellular ribonome, thus allowing for
      the recombination and remodelling of the RNPs (ribonucleoproteins) to generate
      new combinations of functionally related proteins. Thus, post-transcriptional RNA
      operons form the core of the ribonomic operating system in which both their
      control and co-ordination govern outcomes. Within the ribonome, RNA-binding
      proteins control one another's mRNAs to keep the global mRNA environment in
      balance. We argue that these post-transcriptional ribonomic systems provide an
      information management and distribution centre for evolutionary expansion of
      multicellularity in tissues, organs, organisms, and their communities.

PMID- 19152506
TI  - Programming of hypothalamic neuropeptide gene expression in rats by maternal
      dietary protein content during pregnancy and lactation.
AB  - Epidemiological studies show a link between low birthweight and increased
      obesity. In contrast, slow growth during the lactation period reduces obesity
      risk. The present study investigates the potential underlying mechanisms of these
      observations. Rats were established as follows: (i) control animals [offspring of
      control dams fed a 20% (w/v) protein diet], (ii) recuperated animals [offspring
      of dams fed an isocaloric low-protein (8%, w/v) diet during pregnancy and nursed
      by control dams], and (iii) postnatal low protein animals (offspring of control
      dams nursed by low-protein-fed dams). Serum and brains were collected from fed
      and fasted animals at weaning. Expression of hypothalamic energy balance genes
      was assessed using in situ hybridization. Recuperated pups were smaller at birth,
      but caught up with controls by day 21 and gained more weight than controls
      between weaning and 12 weeks of age (P<0.05). At 21 days, they were
      hypoleptinaemic compared with controls in the fed state, with generally
      comparable hypothalamic gene expression. Postnatal low protein offspring had
      significantly lower body weights than controls at weaning and 12 weeks of age
      (P<0.001). At 21 days, they were hypoglycaemic, hypoinsulinaemic and
      hypoleptinaemic. Leptin receptor gene expression in the arcuate nucleus was
      increased in postnatal low protein animals compared with controls. Consistent
      with hypoleptinaemia, hypothalamic gene expression for the orexigenic
      neuropeptides NPY (neuropeptide Y) and AgRP (Agouti-related peptide) was
      increased, and that for the anorexigenic neuropeptides POMC (pro
      opiomelanocortin) and CART (cocaine- and amphetamine-regulated transcript) was
      decreased. These results suggest that the early nutritional environment can
      affect the development of energy balance circuits and consequently obesity risk.

PMID- 19152507
TI  - Cytochrome P450 oxidoreductase participates in nitric oxide consumption by rat
      brain.
AB  - In low nanomolar concentrations, NO (nitric oxide) functions as a transmitter in
      brain and other tissues, whereas near-micromolar NO concentrations are associated
      with toxicity and cell death. Control of the NO concentration, therefore, is
      critical for proper brain function, but, although its synthesis pathway is well
      characterized, the major route of breakdown of NO in brain is unclear. Previous
      observations indicate that brain cells actively consume NO at a high rate. The
      mechanism of this consumption was pursued in the present study. NO consumption by
      a preparation of central glial cells was abolished by cell lysis and recovered by
      addition of NADPH. NADPH-dependent consumption of NO localized to cell membranes
      and was inhibited by proteinase K, indicating the involvement of a membrane-bound
      protein. Purification of this activity yielded CYPOR (cytochrome P450
      oxidoreductase). Antibodies against CYPOR inhibited NO consumption by brain
      membranes and the amount of CYPOR in several cell types correlated with their
      rate of NO consumption. NO was also consumed by purified CYPOR but this activity
      was found to depend on the presence of the vitamin E analogue Trolox (6-hydroxy
      2,5,7,8-tetramethylchromane-2-carboxylic acid), included in the buffer as a
      precaution against inadvertent NO consumption by lipid peroxidation. In contrast,
      NO consumption by brain membranes was independent of Trolox. Hence, it appears
      that, during the purification process, CYPOR becomes separated from a partner
      needed for NO consumption. Cytochrome P450 inhibitors inhibited NO consumption by
      brain membranes, making these proteins likely candidates.

PMID- 19152509
TI  - Clinical effect of low-energy double-pass 1450 nm laser treatment for acne in
      Asians.
AB  - BACKGROUND: While the 1450 nm diode laser is highly effective for the treatment
      of acne, its use is associated with considerable pain. Low-energy, double-pass
      irradiation was attempted as an alternative to prevent the occurrence of pain as
      an adverse effect. PURPOSE: This study aimed to evaluate the clinical efficacy of
      low-energy, double-pass, 1450 nm diode laser treatment in the treatment of acne
      in Asian patients. METHODS: Thirty Japanese patients with inflammatory acne were
      treated with the low-energy, double-pass, 1450 nm diode laser at 2-4-week
      intervals. An open study was performed in patients that underwent at least five
      and up to 10 treatment sessions. The clinical effect was assessed using an acne
      grading scale. RESULTS: Of the 30 patients, 27 completed the study. The mean acne
      grades decreased from 3.9 to 1.4 (P<0.01) in the 27 patients. The pain was
      tolerated by 25 patients, and two patients required local anesthesia. No
      remarkable side effects occurred in any of the patients; all but a few patients
      had transient faint erythema. CONCLUSION: Low-energy, double-pass therapy is an
      alternative method that is beneficial for patients who complain of considerable
      pain. Furthermore, the method may have a lower risk of transient
      hyperpigmentation induced by cryogen spray, even in Asian patients who tend to
      develop inflammatory pigmentation.

PMID- 19152510
TI  - Population reference intervals for minimal erythemal doses in monochromator
      phototesting.
AB  - BACKGROUND/PURPOSE: Monochromator phototesting, to measure the minimal erythemal
      dose (MED), is useful in investigating patients with abnormal photosensitivity at
      different wavelengths. It relies on access to reliable, up-to-date data on the
      MED in normal individuals. The purpose of this study was to determine MED in
      normal subjects at different wavebands and compare these with historical
      controls. METHODS: The study group consisted of 415 normal individuals (349
      males) of skin types I-III living in Scotland. Age range was 18-83 years (median
      31 years). Phototesting was performed using a monochromator at prescribed
      wavelengths from 295 to 430 nm. All calibrations were traceable to the National
      Physical Laboratory. Quality systems were maintained to ISO 9001 and ISO 17025
      international standards and ultraviolet (UV) measurements accredited by the
      United Kingdom Accreditation Service (UKAS). RESULTS: The 95% reference interval
      (99% confidence interval for this) ranged from 6.8 to 27 mJ/cm(2) at 295 nm to
      >82,000 mJ/cm(2) at 430 nm. CONCLUSIONS: Results of the current investigation are
      broadly in agreement with values published 25 years ago by this centre. This
      validates the phototesting process based on the use of monochromators with
      attention to careful control of conditions during UV exposure and MED reading,
      supported by dosimetric calibration.

PMID- 19152511
TI  - Tanning as an addictive behavior: a literature review.
AB  - BACKGROUND: Recent studies have identified reinforcing properties associated with
      tanning and suggest a possible physiologic mechanism and addiction driving
      tanning behavior. OBJECTIVE: This article attempts to synthesize the existing
      literature on tanning and addiction to investigate possible associations.
      METHODS: We investigated a variety of substance dependence models to define what
      constitutes dependence/addiction and to determine how current studies on tanning
      meet these criteria. RESULTS: In some individuals, tanning has met Diagnostic and
      Statistical Manual criteria for a substance-related disorder or tanning-modified
      Cut Down, Annoyed, Guilt, Eye-opener criteria. Trial studies have demonstrated
      the induction of withdrawal symptoms in frequent tanners. LIMITATIONS: Additional
      studies are needed to investigate the associated dependency and addiction more
      fully and to elucidate its similarities to other better-known addictive
      syndromes. DISCUSSION: Tanning is a problem behavior, both as a health risk and
      as a possible dependency. Future studies, especially in the area of cognitive
      mapping and cue-related stimuli are needed. Imaging studies may be important in
      elucidating whether the same areas of the brain are involved in tanning addiction
      as in other addictive syndromes.

PMID- 19152512
TI  - Effect of ultraviolet radiation on the expression of pp38MAPK and furin in human
      keratinocyte-derived cell lines.
AB  - BACKGROUND: Ultraviolet radiation (UVR) is known to induce the activation of
      stress-inflammation signal transduction pathways, and to induce the activity of
      many proteases in skin cells. It is unknown whether the activation of proteases
      such as furin is related to changes in the phosphorylation status of p38MAPK.
      METHODS: The effect of UVR on immortalized keratinocyte (HaCaT) and squamous cell
      carcinoma (Colo16) cells was investigated with respect to cell survival,
      phosphorylation of p38MAPK, and the proprotein convertase, furin. The cells were
      exposed to either a low or a high dose of UVA and/or UVB and the viability was
      monitored over 48 h, along with changes in the intracellular expression of
      p38MAPK and furin. RESULTS: Low-dose UVA (2 kJ/m(2)) and/or UVB (0.2 kJ/m(2))
      radiation had no effect on cell viability, except in UVA-irradiated Colo16 cells.
      High UVA (20 kJ/m(2)) caused a loss of cell viability in HaCaT cells, but not in
      Colo16 cells. The opposite effect was seen in cells exposed to a high UVB dose (2
      kJ/m(2)). The viability of both cell cultures decreased when exposed to high-dose
      UVA+B radiation. UV irradiation downregulated the expression of phosphorylated
      p38 (pp38) in HaCaT cells irrespective of the UV dose and type. In Colo16 cells,
      UV radiation induced pp38 expression in the cells following exposure, with the
      highest increase in cells exposed to high-dose UVA. The expression of furin in UV
      irradiated HaCaT cells was similar to that seen for pp38 expression. In Colo16
      cells, UV radiation induced furin expression, with the highest increase seen in
      cells 24 h after exposure to both high-dose UVB and UVA+B radiation. CONCLUSION:
      The results show that there are differences between the effect of UV types and
      doses on cell function in the keratinocyte-derived cell lines examined in this
      study. The level of furin expression in Colo16 cells correlated to changes in
      pp38 levels in the cells following exposure to UV radiation, but not in HaCaT
      cells. From an improved understanding of the signalling pathways and their
      downstream events and how these may differ as a result of tumorigenesis, it may
      enable the development of inhibitors, which may have therapeutic applications.

PMID- 19152513
TI  - The development of a filter to enhance the efficacy and safety of excimer light
      (308 nm) therapy.
AB  - BACKGROUND: Excimer light (308 nm) therapy is a new ultraviolet (UV) B
      phototherapy for which the efficacy and resulting DNA damage are not well
      established. PURPOSE: To develop an effective and safe phototherapy using the
      excimer lamp, we studied the effects of different light cut-off filters, A and B.
      METHODS: Efficacy was evaluated by measuring apoptosis using fluorescence
      activated cell sorting analysis. DNA damage was evaluated by measuring
      cyclobutane pyrimidine dimers (CPDs). Light sources, including normal wave and
      short wave (SW) excimer light, broad-band (BB) UVB, and narrow-band (NB) UVB,
      were examined using the filters. A human skin equivalent model was also examined.
      RESULTS: The ratio of positive apoptosis to CPD formation normalized to the mean
      induced by NB-UVB was 5.7 using the excimer lamp without a filter, 6.3 using the
      excimer lamp with the A filter, 6.4 using the SW excimer lamp without a filter,
      and 4.2 using the BB-UVB. The A filter reduced CPD formation induced by the
      normal wave and SW excimer lamp. In the human skin equivalent model, the use of
      filters significantly decreased the amount of CPD-positive cells. CONCLUSIONS:
      These findings suggest that using the A filter with the excimer lamp increases
      the efficacy and safety of excimer light therapy.

PMID- 19152514
TI  - A pilot study to assess the efficacy of photodynamic therapy for Japanese
      patients with actinic keratosis in relation to lesion size and histological
      severity.
AB  - BACKGROUND/PURPOSE: Topical 5-aminolevulinic acid (ALA)-based photodynamic
      therapy (PDT) is effective for actinic keratosis (AK); few studies have examined
      Oriental patients. The aim of this study is to assess the efficacy of PDT for the
      treatment of Japanese AK patients classified by lesion size and histological
      severity. METHODS: Thirty patients with solitary AK lesions were divided into two
      groups according to diameter: a small lesion group (SL), diameter < or =10 mm and
      a larger lesion group (LL), diameter >10 mm, and histological severity: Group I
      (mild and moderate) and Group II (severe). After application of 20% ALA for 4 h,
      exposure to an excimer-dye laser at 630 nm was performed at a dose of 50 J/cm(2)
      three times at an interval of 7 days. Therapeutic effects were assessed and
      followed for 12 months. RESULTS: In all 10 SL patients, atypical cells
      disappeared after PDT and did not recur for 12 months. However, for the 20 LL
      patients, recurrence was seen in 2 of the 14 Group I patients, while 4 of 6 Group
      II patients showed residual tumor cells after the first PDT session. CONCLUSION:
      The present study demonstrated that ALA-PDT might be useful for treatment of
      Japanese AK. The therapeutic outcome might depend on the lesion size and the
      histopathological severity.

PMID- 19152515
TI  - Feasibility and accuracy of a newly developed hand-held device with a flat-type
      fluorescent lamp for measuring the minimal erythema dose for narrow-band UVB
      therapy.
AB  - BACKGROUND: Narrow-band ultraviolet B (NB-UVB) for the treatment of refractory
      skin diseases, such as psoriasis and atopic dermatitis, requires an adequate
      irradiation protocol based on the minimal erythema dose (MED) to establish an
      optimal dosage schedule. Although MED can be measured using a systemic-type
      irradiation unit, there are difficulties associated with this device. There is no
      standardized device available to determine the MED for NB-UVB. Here, we compared
      a conventional device with a newly developed device for measuring MED. METHOD:
      MED was measured in 16 psoriasis patients using both a conventional measuring
      device and the newly developed device, which comprised a hand-held NB-UVB (311
      313 nm) flat-type fluorescent lamp with neutral density filters having different
      transmittances ranging from 10% to 90%. This device was designed to be stably
      maintained on the skin surface and to provide a highly accurate measurement with
      only one UV irradiation exposure while also preventing UV radiation from leaking
      to nonirradiated areas. RESULTS: The MED values obtained from each patient were
      the same using both devices. CONCLUSION: One-time irradiation using the new hand
      held device with the NB-UVB flat-type fluorescent lamp is feasible and accurate
      for determining the MED to use in calculating the UV irradiation treatment dose.

PMID- 19152516
TI  - Precise determination of the erythema response of human skin to ultraviolet
      radiation and quantification of effects of protectors.
AB  - BACKGROUND: We describe highly reproducible methods for quantifying the erythema
      response of precisely selected areas (spots) of human skin to graded doses of
      ultraviolet radiation (UVR). These methods have permitted evaluation of the
      efficacy of protectors, such as sulforaphane from crucifers, that defend cells
      through induction of cytoprotective (phase 2) genes. METHODS: Spots on the back
      were precisely located by opaque, adhesive, vinyl templates provided with 16
      circular, 2.0 cm diameter occludable windows. Doses (100-800 mJ/cm(2)) of narrow
      band (311 nm) UVR were administered, and the erythema index (a(*)) was measured
      with a chromometer on treated and control areas, before and after radiation.
      RESULTS: Daily variations in basal a(*) values of each spot were much smaller
      than the differences of a(*) values among spots of one individual, or those of
      corresponding spots among different individuals. The increments in erythema
      responses to UVR (Delta a(*)) were similar despite large variations of basal a(*)
      of spots. The most appropriate measure of UVR-evoked erythema is therefore the
      Delta a(*) value for each spot, which is an independent observational entity.
      Delta a(*) was proportional to UVR dose, and independent of spot location. To
      evaluate effectiveness of protectors against UVR damage we paired horizontally
      adjacent spots for treatment and controls. Vertical or random spot pairing did
      not provide significantly higher consistency. Protective efficacy against UVR
      erythema is appropriately expressed as percent reduction in Delta a(*) values
      upon treatment with inducers. CONCLUSIONS: The protection of skin against UVR
      damage can be quantified precisely from changes in erythema index (Delta a(*))
      obtained with a chromometer.

PMID- 19152517
TI  - Milia complicating bullous polymorphic light eruption.
AB  - Polymorphic light eruption (PLE) is the most common photosensitivity disorder.
      Typically, PLE manifests in the spring or summer months as a recurrent pruritic
      papular and/or vesicular eruption occurring on photoexposed skin areas following
      sun exposure. The milia are caused by proliferative tendencies of the epithelium
      after injury. These may occur in areas of subepidermal bullous eruption. We
      report an original case of bullous PLE complicated by milia. Such association has
      not been reported previously.

PMID- 19152518
TI  - Photodynamic therapy for the treatment of a giant superficial basal cell
      carcinoma.
AB  - A 74-year-old man was referred to our department for the treatment of a 15 x 15
      cm superficial basal cell carcinoma (BCC) on his lumbar region. As surgical
      excision was considered too destructive, photodynamic therapy (PDT) was proposed.
      Methyl 5-aminolevulinate (MAL) cream was applied under occlusion for 3 h before
      illumination with a light-emitting diode lamp with an emission peak of 632 nm, a
      fluence rate of 83.3 mW/cm, and a light dose of 37 J/cm. A second MAL-PDT session
      was repeated 1 week later. The neoplastic area healed in 30 days. No recurrence
      has occurred after a 40-month follow-up period, but clinical observation
      continues. Although surgery still remains the treatment of choice for giant BCC,
      for which the local invasiveness and metastatic potential are well known, we
      offered our patient the option of PDT because we believed that classical surgery
      could hardly provide the same satisfactory outcome. As far as we know, this is
      the first case of giant BCC treated with PDT.

PMID- 19152519
TI  - Narrowband UVB treatment of pigmented purpuric lichenoid dermatitis (Gougerot
      Blum).
AB  - Pigmented purpuric dermatoses are a group of dermatoses characterized clinically
      by pinpoint petechia and purpura on a brown, red or yellow base. Five diseases
      are included in the group of pigmented purpuric eruptions which significantly
      overlap clinically and histologically. Phototherapy in various forms of purpuric
      dermatoses has been reported in literature previously. Here we present a case of
      pigmented purpuric lichenoid dermatitis which rapidly cleared with narrowband UVB
      therapy.

PMID- 19152520
TI  - Acne-photodynamic therapy with intra-lesional injection of 5-aminolevulinic acid.
AB  - Photodynamic therapy (PDT) is a treatment option for acne patients who fail to
      respond to conventional therapy. Although potent, we experience side effects such
      as erythema, exfoliation and dyspigmentation. In attempt to specify treatment and
      shorten the incubation time, we injected 5-aminolevulinic acid (ALA) to the
      individual lesion. The results of intralesional injection ILI-PDT and
      conventional PDT are compared in this study.

PMID- 19152521
TI  - Prevalences of chronic photodermatoses in Scotland.

PMID- 19152523
TI  - Non-odontogenic infections in dentistry.

PMID- 19152524
TI  - Bacterial infections of the oral mucosa.

PMID- 19152525
TI  - Oral mucosal fungal infections.

PMID- 19152526
TI  - Oral viral infections of adults.

PMID- 19152527
TI  - Oral viral infections of children.

PMID- 19152528
TI  - Parasitic infections affecting the oral cavity.

PMID- 19152529
TI  - Non-odontogenic abscesses in the head and neck region.

PMID- 19152530
TI  - Sinusitis.

PMID- 19152531
TI  - Pharyngotonsillitis.

PMID- 19152532
TI  - Respiratory tract infections and pneumonia.

PMID- 19152533
TI  - Infections of the esophagus and the stomach.

PMID- 19152534
TI  - Middle ear infections.

PMID- 19152535
TI  - Facial skin infections.

PMID- 19152536
TI  - Synchrony and cooperation.
AB  - Armies, churches, organizations, and communities often engage in activities-for
      example, marching, singing, and dancing-that lead group members to act in
      synchrony with each other. Anthropologists and sociologists have speculated that
      rituals involving synchronous activity may produce positive emotions that weaken
      the psychological boundaries between the self and the group. This article
      explores whether synchronous activity may serve as a partial solution to the free
      rider problem facing groups that need to motivate their members to contribute
      toward the collective good. Across three experiments, people acting in synchrony
      with others cooperated more in subsequent group economic exercises, even in
      situations requiring personal sacrifice. Our results also showed that positive
      emotions need not be generated for synchrony to foster cooperation. In total, the
      results suggest that acting in synchrony with others can increase cooperation by
      strengthening social attachment among group members.

PMID- 19152537
TI  - We infer rather than perceive the moment we decided to act.
AB  - A seminal experiment found that the reported time of a decision to perform a
      simple action was at least 300 ms after the onset of brain activity that normally
      preceded the action. In Experiment 1, we presented deceptive feedback (an
      auditory beep) 5 to 60 ms after the action to signify a movement time later than
      the actual movement. The reported time of decision moved forward in time linearly
      with the delay in feedback, and came after the muscular initiation of the
      response at all but the 5-ms delay. In Experiment 2, participants viewed their
      hand with and without a 120-ms video delay, and gave a time of decision 44 ms
      later with than without the delay. We conclude that participants' report of their
      decision time is largely inferred from the apparent time of response. The
      perception of a hypothetical brain event prior to the response could have, at
      most, a small influence.

PMID- 19152538
TI  - Tonic activity level in the right prefrontal cortex predicts individuals' risk
      taking.
AB  - Human risk taking is characterized by a large amount of individual heterogeneity.
      In this study, we applied resting-state electroencephalography, which captures
      stable individual differences in neural activity, before subjects performed a
      risk-taking task. Using a source-localization technique, we found that the
      baseline cortical activity in the right prefrontal cortex predicts individual
      risk-taking behavior. Individuals with higher baseline cortical activity in this
      brain area display more risk aversion than do other individuals. This finding
      demonstrates that neural characteristics that are stable over time can predict a
      highly complex behavior such as risk-taking behavior and furthermore suggests
      that hypoactivity in the right prefrontal cortex might serve as a dispositional
      indicator of lower regulatory abilities, which is expressed in greater risk
      taking behavior.

PMID- 19152539
TI  - The cost of anchoring on credit-card minimum repayments.

PMID- 19152540
TI  - The role of spatial attention in nonconscious processing: a comparison of face
      and nonface stimuli.
AB  - Recent findings from the masked priming paradigm have revealed a surprising
      influence of higher-level cognitive systems (i.e., attention) on nonconscious
      cognitive processes. These data have effectively undermined the long-standing
      assumption in cognitive science that nonconscious processes are carried out
      independently of attention and have quickly led to the opposite view that
      attention is a prerequisite for nonconscious processes. Here we present evidence
      for a middle position by showing that the dependence of nonconscious processes on
      attention varies with the type of information to be processed. Specifically, we
      found that nonconsciously perceived faces engaged cognitive processes regardless
      of attention, whereas nonface stimuli engaged cognitive processes only when
      attended. These qualitatively different patterns suggest two distinct processing
      routes: one that is modulated by visual attention and one that is not.

PMID- 19152541
TI  - Driving under the influence (of stress): evidence of a regional increase in
      impaired driving and traffic fatalities after the september 11 terrorist attacks.
AB  - Did the September 11 terrorist attacks elicit a subsequent increase in traffic
      fatalities? Gigerenzer (2004) argued that decreases in flying and increases in
      driving in the 3 months after the attacks led to 353 "surplus" traffic
      fatalities. We applied a more systematic analysis to the same data and found no
      evidence of a significant increase in miles driven or of a significant increase
      in traffic fatalities. However, we did find evidence for a regional effect of the
      attacks on driving behaviors. We hypothesized that geographic proximity to the
      attacks increased stress, which in turn decreased driving quality. Our analyses
      revealed that in the last 3 months of 2001, the Northeast exhibited a significant
      increase in traffic fatalities, as well as a significant increase in fatal
      accidents involving an alcohol- or drug-related citation. Increased stress
      related to physical proximity to the attacks may explain the increase in traffic
      fatalities.

PMID- 19152542
TI  - Effects of aging on functional connectivity of the amygdala for subsequent memory
      of negative pictures: a network analysis of functional magnetic resonance imaging
      data.
AB  - Aging is associated with preserved enhancement of emotional memory, as well as
      with age-related reductions in memory for negative stimuli, but the neural
      networks underlying such alterations are not clear. We used a subsequent-memory
      paradigm to identify brain activity predicting enhanced emotional memory in young
      and older adults. Activity in the amygdala predicted enhanced emotional memory,
      with subsequent-memory activity greater for negative stimuli than for neutral
      stimuli, across age groups, a finding consistent with an overall enhancement of
      emotional memory. However, older adults recruited greater activity in anterior
      regions and less activity in posterior regions in general for negative stimuli
      that were subsequently remembered. Functional connectivity of the amygdala with
      the rest of the brain was consistent with age-related reductions in memory for
      negative stimuli: Older adults showed decreased functional connectivity between
      the amygdala and the hippocampus, but increased functional connectivity between
      the amygdala and dorsolateral prefrontal cortices. These findings suggest that
      age-related differences in the enhancement of emotional memory might reflect
      decreased connectivity between the amygdala and typical subsequent-memory
      regions, as well as the engagement of regulatory processes that inhibit emotional
      responses.

PMID- 19152543
TI  - The irony of harmony: intergroup contact can produce false expectations for
      equality.
AB  - Positive intergroup contact has been a guiding framework for research on reducing
      intergroup tension and for interventions aimed at that goal. We propose that
      beyond improving attitudes toward the out-group, positive contact affects
      disadvantaged-group members' perceptions of intergroup inequality in ways that
      can undermine their support for social change toward equality. In Study 1,
      participants were assigned to either high- or low-power experimental groups and
      then brought together to discuss either commonalities between the groups or
      intergroup differences. Commonality-focused contact, relative to difference
      focused contact, produced heightened expectations for fair (i.e., egalitarian)
      out-group behavior among members of disadvantaged groups. These expectations,
      however, proved unrealistic when compared against the actions of members of the
      advantaged groups. Participants in Study 2 were Israeli Arabs (a disadvantaged
      minority) who reported the amount of positive contact they experienced with Jews.
      More positive intergroup contact was associated with increased perceptions of
      Jews as fair, which in turn predicted decreased support for social change.
      Implications for social change are considered.

PMID- 19152544
TI  - On the presumption of evidentiary independence: can confessions corrupt
      eyewitness identifications?
AB  - A confession is potent evidence, persuasive to judges and juries. Is it possible
      that a confession can also affect other evidence? The present study tested the
      hypothesis that a confession will alter eyewitnesses' identification decisions.
      Two days after witnessing a staged theft and making an identification decision
      from a lineup that did not include the thief, participants were told that certain
      lineup members had confessed or denied guilt during a subsequent interrogation.
      Among those participants who had made a selection but were told that another
      lineup member confessed, 61% changed their identifications. Among those
      participants who had not made an identification, 50% went on to select the
      confessor when his identity was known. These findings challenge the presumption
      in law that different forms of evidence are independent and suggest an important
      overlooked mechanism by which innocent confessors are wrongfully convicted:
      Potentially exculpatory evidence is corrupted by a confession itself.

PMID- 19152545
TI  - The "instrumentality" heuristic: why metacognitive difficulty is desirable during
      goal pursuit.
AB  - The literature overwhelmingly demonstrates that feelings of ease are good and
      that objects that are easy to process are much liked. We propose, and demonstrate
      across three experiments, that this is not the case when people are pursuing a
      goal. This is because people pursuing a goal (e.g., "become kinder") usually
      invest efforts in whichever means (e.g., donate to a particular charity) they
      perceive as most instrumental for attaining their goal. Consequently, in their
      minds there is a correspondence between instrumentality of a means and feelings
      of effort. This correspondence becomes reversed in people's minds during goal
      pursuit, and they also come to view an object that is associated with feelings of
      effort rather than ease as more instrumental for goal attainment and consequently
      more desirable. When an object is not a means to fulfill an accessible goal, or
      when goals relating to the means are not accessible, subjective feelings of ease
      improve evaluation, as found in previous research on ease of processing.

PMID- 19152546
TI  - Letter from the editor.

PMID- 19152547
TI  - The effect of aromatase inhibitors on bone metabolism.
AB  - Aromatase inhibitors increase the disease-free survival in patients with receptor
      positive breast cancer. Aromatase is a cytochrome P450 enzyme complex catalysing
      the conversion of androgens to oestrogens. These properties cause a significant
      increase in bone loss. In this MiniReview, we present data from the aromatase
      inhibitor studies and the studies designed to investigate aromatase inhibitor
      effect on bone metabolism. At the cellular level, oestrogen has profound effects
      on both osteoblasts and osteoclasts. Oestrogen decreases the osteoblastic
      production of resorptive cytokines and simultaneously increases the production of
      antireceptive cytokines, which leads to increased osteoclastic apoptosis and
      increased osteoblastic activity. Aromatase inhibitors inhibit the endogenous
      production of oestrogen by 50-90%. Studies designed to look at the effect of
      aromatase inhibitors on bone mineral density have shown a significant decrease in
      bone mineral density of the femoral neck in the aromatase inhibitor groups
      compared to placebo groups. Placebo-controlled studies lack statistical power to
      detect changes in fracture incidence; however, aromatase inhibitors increase the
      incidence of fractures in comparison with tamoxifen. We conclude that treatment
      with aromatase inhibitors leads to an increased bone loss and thus an increase in
      the risk of fractures in women with breast cancer.

PMID- 19152548
TI  - Capsaicin- and mustard oil-induced extracellular signal-regulated protein kinase
      phosphorylation in sensory neurons in vivo: effects of neurokinins 1 and 2
      receptor antagonists and of a nitric oxide synthase inhibitor.
AB  - Stimulation of primary sensory neurons with capsaicin or mustard oil leads to
      phosphorylation of extracellular signal-regulated protein kinase 1/2 (p-ERK1/2)
      via activation of transient receptor potential V1 (TRPV1) or TRPA1, respectively.
      p-ERK1/2 was determined by Western immunoblotting in the dorsal root ganglia and
      in the sciatic nerve of rats following either systemic or perineural capsaicin
      treatment, or mustard oil application to the hind paw skin. To investigate the
      possible involvement of neurokinin 1 (NK(1)) and NK(2) receptors as well as of
      nitric oxide, the selective antagonists, SR140333 for NK(1) and SR48968 for
      NK(2), and the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl
      ester (L-NAME), were employed. The increase of p-ERK1/2 after systemic capsaicin
      treatment was markedly attenuated by SR140333, while only the increase in the
      dorsal root ganglia was impaired by SR48968; in contrast, inhibition of nitric
      oxide synthase had no effect. Perineural capsaicin induced an increase in p
      ERK1/2 in the ipsilateral sciatic nerve and in the dorsal root ganglia. This
      effect was not influenced by SR140333 or L-NAME. We found for the first time that
      mustard oil application to the hind paw skin caused an increase in p-ERK1/2 in
      the sciatic nerve and in the dorsal root ganglia and only the phosphorylation in
      the latter was attenuated by SR140333 while L-NAME showed no effect. From the
      present results, it may be assumed that capsaicin- or mustard oil-induced p
      ERK1/2 in sensory neurons is not solely directly linked to TRPV1 or TRPA1
      channels, but under certain conditions NK(1)- and NK(2)-mediated mechanisms are
      involved.

PMID- 19152549
TI  - Effects of nimesulide, acetylsalicylic acid, ibuprofen and nabumetone on
      cyclooxygenase-1- and cyclooxygenase-2-mediated prostanoid production in healthy
      volunteers ex vivo.
AB  - : The beneficial actions of non-steroidal anti-inflammatory drugs (NSAIDs) have
      been associated with inhibition of cyclooxygenase-2 (COX-2), whereas some of
      their adverse effects are associated mainly with inhibition of COX-1. Selective
      COX-2 inhibitors reduce the risk of gastrointestinal adverse events, but increase
      the risk of thromboembolic events pointing to importance of optimal COX-1/COX-2
      inhibition in drug safety. We compared the effects of acetylsalicylic acid,
      ibuprofen, nabumetone and nimesulide on COX-1 and COX-2 pathways in healthy
      volunteers in an ex vivo set-up using single oral doses commonly used to treat
      acute pain. In a randomized, double-blind four-phase cross-over study, 15 healthy
      volunteers were given orally a single dose of either acetylsalicylic acid 500 mg,
      ibuprofen 400 mg, nabumetone 1 g or nimesulide 100 mg. Blood samples were drawn
      before and 1, 3, 6, 24 and 48 hr after the drug for the assessment of COX-1 and
      COX-2 activity. COX-1 activity was measured as thromboxane(2) production during
      blood clotting and COX-2 activity as endotoxin-induced prostaglandin E(2)
      synthesis in blood leucocytes. The data show that after a single oral dose these
      four NSAIDs have different profiles of action on COX-1 and COX-2. As expected,
      acetylsalicylic acid appeared to be COX-1-selective and ibuprofen effectively
      inhibited both COX-1 and COX-2. Nabumetone showed only a slight inhibitory effect
      on COX-1 and COX-2. Nimesulide caused almost complete suppression of COX-2
      activity and a partial reduction of COX-1 activity. This confirms the relative
      COX-2 selectivity of nimesulide.

PMID- 19152550
TI  - Ethylene glycol toxicity presenting with non-anion gap metabolic acidosis.
AB  - Ethylene glycol classically produces an elevated anion gap metabolic acidosis. We
      report a series of patients with ethylene glycol toxicity with a component of non
      anion gap metabolic acidosis without known associated confounding factors. A
      retrospective review of Poison Control Center records were searched more than 8
      years (2000-2007) for ethylene glycol and antifreeze. Cases were reviewed and
      excluded for miscoding, information calls, animal exposures, or non-ingestion
      exposures. The bicarbonate gap, or delta ratio (DR), was calculated using the
      formula: DR = (AG - 12)/[24 - measured serum where anion gap (AG) = [Na(+)] -
      [Cl(-)] - , all in mEq/l. Non-anion gap metabolic acidosis was considered present
      when the DR < 1. Of 254 cases, 175 were excluded. Of the remaining 79 cases, 14
      had a component of non-anion gap metabolic acidosis at presentation. Their
      calculated anion gap was 14-28, and measured serum ranged from 2-20 mEq/l. A
      normal anion gap was present in two patients who presented with non-anion gap
      metabolic acidosis. The DR ranged from 0.28-0.95. Seven out of 14 patients with
      non-anion gap metabolic acidosis had elevated serum [Cl(-)]. In the other cases,
      no explanation for the non-anion gap metabolic acidosis could be determined. The
      absence of a significant anion gap elevation in the setting of metabolic acidosis
      after ethylene glycol ingestion without other confounding factors (such as
      ethanol, lithium carbonate or bromide) has not previously been recognized.
      Clinicians should be aware of the potential for non-anion gap metabolic acidosis
      in patients with ethylene glycol toxicity, and should not exclude the diagnosis
      in patients who present with a non-anion gap metabolic acidosis. Further study is
      needed to determine the mechanisms by which this occurs.

PMID- 19152551
TI  - Fatal acute endosulfan toxicity: a case report.
AB  - Endosulfan is an organochlorine pesticide. It is banned in the USA and Europe,
      but use is unrestricted for insect control. Endosulfan causes many intentional
      and unintentional toxicities in developing countries and in Turkey. Acute
      exposure to endosulfan has rarely been reported in deaths due to ingestion. Here,
      a fatality of 61-year-old woman of a family who was poisoned due to ingestion of
      endosulfan has been reported. Based on autopsy findings, patient history and
      toxicological results, the cause of death was determined to be acute intoxication
      of endosulfan and the manner, unintentional toxicities. Endosulfan has
      histopathological toxic effects on many organs and this toxic effect occurs
      within a short period after ingestion. To prevent endosulfan poisoning, the usage
      of it must be restricted and even prohibited. To prevent death and to accelerate
      improvement, the organs that have more apparent histopathological injury should
      be considered and early and intensive supportive treatment be initiated.

PMID- 19152552
TI  - Circadian levels of serotonin in plasma and brain after oral administration of
      tryptophan in rats.
AB  - Serotonin, one of the most important neurotransmitters in the central nervous
      system, is synthesized by the amino acid, tryptophan. Given that this essential
      amino acid is consumed in the diet, the aim of this study was to evaluate the
      effect of orally administered L-tryptophan (125 mg/kg) on circadian variations in
      the levels of serotonin in brain and plasma. We used male Wistar rats of 14 +/- 2
      weeks of age (n = 240), maintained under conditions of a 12-hr light:dark cycle,
      and food and water ad libitum. Tryptophan administration was by gavage in a daily
      single dose at 7 p.m. for 7 days. The serotonin levels were measured by ELISA
      every hour at night (8 p.m. to 8 a.m.) and every 4 hr during daytime (8 a.m. to 8
      p.m.). The results show that in both the tryptophan-treated and untreated groups
      the highest values appeared during the beginning of the darkness with a peak at
      9, 10 and 11 p.m. in controls, and at 9 p.m. in the tryptophan-treated group.
      After tryptophan administration, the levels of serotonin were significantly
      higher in the plasma and all the brain regions analysed than in the control
      group. This increase of serotonin levels was greater in the pineal gland than in
      other brain regions, and the least in plasma. In conclusion, oral administration
      of tryptophan during 7 days enhances serotonin levels over a 24-hr period, and
      produces an advance in the peak of serotonin in both plasma and different brain
      regions.

PMID- 19152553
TI  - Effects on lipid peroxidation and antioxidative enzymes of Euonymus alatus in
      cultured rat hepatocytes.
AB  - The Euonymus alatus (Thunb.) Sieb. has long been used as a crude drug. In this
      paper, we investigate the effects of E. alatus on cultured hepatocyte cell system
      and lipid peroxidation in hydrogen peroxide (H(2)O(2)) treatment conditions. The
      study covers the physiological activity (the antioxidative activity and the
      nitrite-scavenging effect) of E. alatus. H(2)O(2) that can produce intracellular
      free radical was used for inducer of the peroxidation of cellular lipids.
      Treatment of E. alatus attenuated in cell killing enhanced by increasing
      concentrations of H(2)O(2). The increased malondialdehyde level induced by
      H(2)O(2) treatment was reduced by pre-treatment of E. alatus. Furthermore,
      addition of E. alatus in cell culture medium significantly reduced cell killing
      and content of intracellular antioxidants. Changes in nitrite-scavenging effect
      of E. alatus at various concentrations (5-25 mg/ml) and various pH levels (pH
      1.2, 4.2 and 6.0) were also observed. The present study was also done to
      investigate the effects of E. alatus on cultured hepatocyte cell system, H(2)O(2)
      induced cytotoxicity and antioxidative enzyme activities, including catalase,
      superoxide dismutase, glutathione peroxidase and glutathione S-transferase in
      H(2)O(2 )treatment conditions. E. alatus treatment had significant protective or
      elevating activities on these antioxidative enzyme activities compared to a
      normal group. The results indicate that E. alatus provides a strong antioxidant
      protection of cells against H(2)O(2)-induced oxidative stress.

PMID- 19152554
TI  - Evaluation of cytotoxic and cytostatic effects in Saccharomyces cerevisiae by
      poissoner quantitative drop test.
AB  - Biological models have long been used to establish the cytotoxicity and
      cytostaticity of natural and/or synthetic chemical compounds. Current assay
      techniques, however, typically require the use of expensive technological
      equipment or chemical reagents, or they lack adequate testing sensitivity. The
      poissoner quantitative drop test (PQDT) assay is a sensitive, inexpensive and
      accurate method for evaluation of cytotoxicity and/or cytostatic effects of
      multiple chemical compounds in a single experiment. In this study, the
      sensitivity of the PQDT assay was evaluated in a wild-type Saccharomyces
      cerevisiae strain using 4-nitroquinoline-N-oxide (4-NQO) and methyl
      methanesulfonate (MMS), both cytotoxic and genotoxic standard compounds, and
      cytostatic 5-fluorouracil, an antitumoral drug. Yeast cell colony growth was
      measured in culture media containing increasing concentrations of the three
      chemical agents. The results showed that the PQDT assay was able to clearly
      differentiate the cytotoxic effect of 4-NQO and MMS from the cytostatic effect of
      5-fluorouracil. Interestingly, the cytostatic effect of 5-fluorouracil followed
      an exponential decay curve with increasing concentrations, a phenomenon not
      previously described for this drug. The PQDT assay, in this sense, can be applied
      not only for cytotoxic/cytostatic assays, but also for pharmacodynamic studies
      using Saccharomyces cerevisiae as a model.

PMID- 19152556
TI  - Accuracy and quality of immunization information systems in forty-one low income
      countries.
AB  - OBJECTIVES: To measure the accuracy and quality of immunization information
      systems in a range of low-income countries eligible to receive GAVI support.
      METHODS: The Data Quality Audit (DQA) uses a WHO validated, standard methodology
      to compare data collected from health unit (HU) records of immunizations
      administered with reports of immunizations at central level and to collect
      quality indicators of the reporting system. The verification factor (VF), as a
      measure of accuracy, expresses the proportion of immunizations reported at
      national level that can be tracked down to the HU. A VF of 80% or above entitles
      countries to receive additional GAVI financial support. Quality indicators are
      assigned points which were summed to obtain quality scores (QS) at national,
      district and HU levels. DQAs included here were conducted between 2002 and 2005
      in 41 countries, encompassing 1082 primary healthcare units in 188 randomly
      selected districts. RESULTS: Almost half of countries obtained a VF below 80% and
      only nine showed consistently high VF and QS scores. The most frequent weaknesses
      in the information systems were inconsistency of denominators used to estimate
      coverage, poor availability of guidelines (e.g. for late reporting), incorrect
      estimations of vaccine wastage and lack of feedback on immunization performance.
      In all six countries that failed a first DQA and undertook a second DQA, the VF
      and all QSs improved, not all of them statistically significantly. CONCLUSIONS:
      The DQA is a diagnostic tool to reveal a number of crucial problems that affect
      the quality of immunization data in all tiers of the health system. It identifies
      good performance at HU and district levels which can be used as examples of best
      practices. The DQA methodology brings data quality issues to the top of the
      agenda to improve the monitoring of immunization coverage.

PMID- 19152557
TI  - Community intervention to promote rational treatment of acute respiratory
      infection in rural Nepal.
AB  - OBJECTIVE: To evaluate a community education program about treatment of acute
      respiratory infection (ARI). METHODS: First, community case definitions for
      severe and mild ARI were developed. The intervention was then evaluated using a
      controlled before-and-after design. Household surveys collected data about ARI
      treatment in 20 clusters, each based around a school and health facility.
      Treatment indicators included percentages of cases attending health facilities
      and receiving antibiotics. The intervention consisted of an education program in
      schools culminating in street theater performances, discussions with mothers
      after performances and training for community leaders and drug retailers by
      paramedics. The intervention was conducted in mid-2003. Indicators were measured
      before the intervention in Nov/Dec 2002 and again in Dec 2003/Jan 2004. RESULTS:
      Two thousand and seven hundred and nineteen households were surveyed and 3654
      under-fives were identified, of whom 377 had severe ARI. After implementing the
      intervention, health post (HP) attendance rose by 13% in under-fives with severe
      ARI and fell by 9% in under-fives with mild ARI (test of interaction, P = 0.01).
      Use of prescribed antibiotics increased in under-fives with severe ARI by 21% but
      only by 1% in under-fives with mild ARI (test of interaction, P = 0.38).
      Irrespective of ARI severity, the use of non-prescribed antibiotics dropped by 5%
      (P = 0.002), and consultation with female community health volunteers (FCHVs)and
      use of safe home remedies increased by 6.7% (P not estimated) and 5.7% (P =
      0.008) respectively. CONCLUSION: The intervention was implemented using local
      structures and in difficult circumstances, yet had a moderate impact. Thus it has
      the potential to effect large scale changes in behaviour and merits replication
      elsewhere.

PMID- 19152558
TI  - Access, sources and value of new medical information: views of final year medical
      students at the University of Nairobi.
AB  - OBJECTIVES: To evaluate final year medical students' access to new medical
      information. METHOD: Cross-sectional survey of final year medical students at the
      University of Nairobi using anonymous, self-administered questionnaires. RESULTS:
      Questionnaires were distributed to 85% of a possible 343 students and returned by
      44% (152). Half reported having accessed some form of new medical information
      within the previous 12 months, most commonly from books and the internet. Few
      students reported regular access; and specific, new journal articles were rarely
      accessed. Absence of internet facilities, slow internet speed and cost impeded
      access to literature; and current training seems rarely to encourage students to
      seek new information. CONCLUSION: Almost half the students had not accessed any
      new medical information in their final year in medical school. This means they
      are ill prepared for a career that may increasingly demand life-long, self
      learning.

PMID- 19152559
TI  - Isolation and culture of ovine and bubaline small and large pre-antral follicles:
      effect of cyclicity and presence of a dominant follicle.
AB  - Studies were conducted to examine the effects of the cyclicity and the presence
      of a dominant follicle (DF) in ovary on the recovery and in vitro growth of pre
      antral follicles (PFs) in sheep and buffalo. Small pre-antral follicles (SPFs,
      100-250 microm) and large pre-antral follicles (LPFs, 250-450 microm) were
      isolated from slaughterhouse ovaries in the breeding seasons by a mechanical and
      enzymatic method. The sheep and buffalo PFs were cultured in vitro for 6 and 15
      days, respectively, and examined for their growth, survival and antrum formation
      rates and growth rates of oocytes in cultured pre-antral follicles. The follicles
      of the sheep and buffalo were recovered and cultured simultaneously within
      replicates. The recovery rates (number per ovary) of both SPFs and LPFs were
      significantly (p < 0.05) higher in cyclic ewes (SPFs: 22.0 +/- 3.3 vs 12.1 +/-
      2.6 and LPFs: 16.0 +/- 3.6 vs 9.2 +/- 1.8) and buffaloes (SPFs: 9.2 +/- 1.3 vs
      4.1 +/- 1.0 and LPFs: 10.3 +/- 2.7 vs 5.4 +/- 0.7) compared with those recovered
      from acyclic ones. Presence of a DF in ovary significantly (p < 0.05) reduced the
      recovery rates of LPFs in ewes (9.06 +/- 2.7 vs 16.4 +/- 3.8) but had no effect
      in buffalo. Cyclicity of animals or follicular dominance had no effects on in
      vitro growth, survival and antrum formation rates and growth rates of oocytes in
      cultured PFs of SPFs and LPFs in both sheep and buffalo. The in vitro growth,
      survival and antrum formation rates of LPFs and growth rates of oocytes in
      cultured LPFs were significantly (p < 0.05) higher than those observed in SPFs in
      both sheep and buffalo. The overall recovery and growth rates of the PFs were
      lower in buffaloes compared with ewes.

PMID- 19152561
TI  - Special Care Dentistry Association consensus statement on sedation, anesthesia,
      and alternative techniques for people with special needs.
AB  - Many people with special needs (PSN) have difficulty having good oral health or
      accessing oral health services because of a disability or medical condition. The
      number of people with these conditions living in community settings and needing
      oral health services is increasing dramatically due to advances in medical care,
      deinstitutionalization, and changing societal values. Many of these individuals
      require additional supports beyond local anesthesia in order to receive dental
      treatment services. The purpose of this consensus statement is to focus on the
      decision-making process for choosing a method of treatment or a combination of
      methods for facilitating dental treatment for these individuals. These guidelines
      are intended to assist oral health professionals and other interested parties in
      planning and carrying out oral health treatment for PSN. Considerations for
      planning treatment and considerations for each of several alternative modalities
      are listed. Also discussed are considerations for the use of combinations of
      modalities and considerations for the repeated or frequent use of these
      modalities. Finally, the need to advocate for adequate education and
      reimbursement for the full range of support alternatives is addressed. The
      Special Care Dentistry Association (SCDA) is dedicated to improving oral health
      and well being of PSN. The SCDA hopes that these guidelines can help oral health
      professionals and other interested individuals and groups to work together to
      ensure that PSN can achieve a "lifetime of oral health."

PMID- 19152562
TI  - A review of guidelines for sedation, anesthesia,and alternative interventions for
      people with special needs.
AB  - There are significant numbers of people in our society with disabilities or other
      special needs. Their number and percentage are growing, in some cases,
      dramatically. Many of these individuals need special support in order to receive
      dental treatment. Modalities that can be used to provide dental treatment include
      pharmacological approaches to produce various levels of sedation or anesthesia.
      In addition to the use of medications, there are also techniques that employ
      behavioral or psychological interventions. In some circumstances, physical
      support or protective stabilization is used. There are also social supports and
      prevention strategies that can impact the individual's preparation for and need
      for dental treatment. This review of the numerous guidelines, which have been
      published for the use of sedation and anesthesia to facilitate the delivery of
      dental treatment, indicates that there are fewer guidelines for the inclusion of
      behavioral or psychological interventions or for the incorporation of social
      supports or prevention strategies. In addition, most published guidelines do not
      include considerations for people with special needs. There is a need for
      increased research and documentation of combined treatment modalities, and these
      combined approaches need to be incorporated into guidelines for patient care for
      people with special needs. There is also a need to advocate for reimbursement
      systems that support all appropriate treatment options so that practitioners can
      be free to recommend treatment options based on the efficacy and safety of each
      option.

PMID- 19152563
TI  - The dental patient with special needs: a review of indications for treatment
      under general anesthesia.
AB  - General anesthesia (GA) can play an important role in the facilitation of dental
      treatment for individuals who present with challenging behaviors. This article
      presents a review of the literature discussing indications for the utilization of
      GA in the treatment of dental patients with special needs.

PMID- 19152564
TI  - Risks of general anesthesia for the special needs dental patient.
AB  - The risk of dental rehabilitation under general anesthesia has multiple
      contributing factors. The literature has addressed the general anesthetic risk of
      dental general anesthesia and sedation in the operating room and the office
      settings, but more studies are needed to address the special needs population in
      particular. There is still a great need for more studies to assess the risk
      versus benefit for special need population as well as to stratify such risk in
      order to assist care providers in decision making as well as in sharing such risk
      concerns with patients, caretakers, and guardians. One recommended approach is to
      conduct a national retrospective study of patients treated under general
      anesthesia in the past 10 years in all the various settings and assess the
      associated risks and complications related to their physical status and the
      underlying physical and mental disabilities. The product of such a study could be
      a stratification of risk versus benefit as well as some guidelines for decision
      making as far as which kind of procedures should be conducted under general
      anesthesia while weighing the level of risk for the particular patient. Although
      access to care is not a direct risk factor, it can certainly deter timely
      treatment and intervention for patients with special needs.

PMID- 19152565
TI  - Providing deep sedation and general anesthesia for patients with special needs in
      the dental office-based setting.
AB  - This article discusses the issues of morbidity and mortality associated with deep
      sedation and general anesthesia specifically in the dental office-based setting
      for patients with special needs (PSN). A focused review of a particular
      environment and patient population was challenging as it was difficult to
      identify articles that discuss the unique scope of this subject. During the
      review of the literature, no article was identified that discussed this exact
      topic. There were articles that discussed the delivery of general anesthesia for
      PSN in an outpatient setting and associated issues of morbidity and mortality.
      There were also articles and sources of information that discussed the delivery
      of general anesthesia for other patient populations in the office-based setting.
      In an effort to support the scope of this article, some of these articles are
      discussed as they pertain to the subject of this article. In addition, an
      analysis of the author's practice over a 4-year period is discussed in an effort
      to present relevant data per the scope of this article. After reviewing the
      literature and the author's clinical practice, it appears that the incidence of
      mortality for PSN in the dental office-based setting is minimal and the incidence
      of morbidity for this same population is limited to relatively minor events.
      Ultimately, it was concluded that the delivery of general anesthesia for PSN in
      the dental office-based setting can be considered a very safe and successful
      procedure.

PMID- 19152566
TI  - Social supports and prevention strategies as adjuncts and alternatives to
      sedation and anesthesia for people with special needs.
AB  - People with special needs are assuming a more prominent place in our society. The
      number of people living in communities with medical, physical, and psychological
      conditions is increasing dramatically. In spite of the advances that people with
      special needs have made in recognition of their right to live in society and
      access services open to other people, their oral health is still significantly
      poorer than that of other groups. There are a number of modalities that can
      complement or replace pharmacological interventions and allow individuals to have
      dental treatment in a dental office or clinic. These include behavioral or
      psychological interventions and social support and prevention strategies. Social
      supports include care management and integration of oral health services with
      general health and social service systems. Preventive programs using modern
      "medical model" oral health prevention strategies also have the potential to
      reduce the burden of disease among people with special needs and therefore reduce
      the need for dental procedures. A social support system using community-based
      Dental Hygienists acting as Dental Coordinators, is described along with outcomes
      demonstrating improved oral health for people with special needs living in
      community residential care facilities. Combined social support systems and
      community prevention strategies have the potential to reduce the need for
      pharmacological interventions in order to maintain oral health in populations of
      people with special needs. Social supports and modern preventive strategies must
      be included in the range of options available in communities in order to improve
      and maintain oral health for people with special needs.

PMID- 19152567
TI  - Understanding basic behavioral support techniques as an alternative to sedation
      and anesthesia.
AB  - Patients with special needs often present a challenge for the dental care team.
      The exacting and surgical nature of dental procedures requires significant
      patient cooperation to ensure the safe delivery of care. Some individuals who
      have special care needs have difficulty cooperating during treatment, thus
      creating a potentially harmful situation. Modern dentistry, particularly
      pediatric dentistry, provides the dental team with a variety of strategies
      designed to enable the team to safely provide comprehensive care in the least
      restrictive manner. These techniques range from tell-show-do, to medical
      stabilization, to general anesthesia. The effective use of noninvasive,
      nonpharmacologic behavioral guidance/support techniques cannot only avoid the
      need for sedation or general anesthesia, they can teach the patient to develop
      coping skills that may enable them to receive comprehensive care in a traditional
      dental setting over a lifetime. Unfortunately, many providers are inadequately
      trained in behavioral support strategies. This paper presents a review of
      noninvasive, nonpharmacologic behavioral support techniques with discussion
      regarding their application to persons with special care needs.

PMID- 19152568
TI  - Psychological treatment of fearful and phobic special needs patients.
AB  - Dental fears and phobias trouble patients with and without special needs, and
      they are a problem for dentists, as well. This article reviews current research
      and literature related to methods used to alleviate dental fear and concludes
      that while some important psychological methods are available, much work is left
      to be done in this area. It is clear that there is an important role for
      psychological and behavioral input to the dentist-patient interaction. While
      dental phobia represents a class of special needs itself, patients with other
      important disabilities (e.g., physical or cognitive impairments) are sometimes
      comorbidly phobic, a condition often missed or misdiagnosed by treating
      practitioners. Office-based techniques that focus on relaxation, breathing,
      imagery, hypnosis, and effective use of operatory language are described. The
      methods advocated here can be used with patients having mild or moderate
      cognitive impairments. Readings are recommended for the dentist or auxiliary
      practitioner interested in learning these techniques.

PMID- 19152569
TI  - Consent, restraint, and people with special needs: a review.
AB  - Dentists providing treatment to individuals with developmental disabilities are
      often faced with unique medical/legal issues. Obtaining informed consent when a
      patient does not have capacity can be an involved process. Issues regarding
      therapeutic aides used for immobilization (i.e., restraint) during treatment may
      further complicate the situation. This area is controversial and has even
      resulted in legal difficulties for some dentists. Several topics related to the
      use of restraint are addressed in this article. A review of the literature and
      applicable laws pertaining to consent issues for people with special needs is
      presented and appropriate use of medical immobilization is discussed. Existing
      guidelines are reviewed. Informed consent and the use of restraint should be
      incorporated into overall guidelines for the use of anesthesia, sedation, and
      alternative behavior management techniques in providing dental care to patients
      with special needs.

PMID- 19152571
TI  - Scar assessment scales: a dermatologic overview.
AB  - BACKGROUND: This overview critically compares subjective assessment tools and
      available objective measurement tools with potential devices becoming available.
      Our goal is to lay out the benefits of each scar assessment scale in order to
      propose good management skills for scars along with strong metric skills.
      METHODS: Classifying a scar is important in daily clinical practice. Ultimately
      choosing which treatment modality best fits can become a challenge. Scar
      classification needs a more detailed and systematic approach. We researched all
      different factors contributing to scar formation to come up with a more detailed
      criteria. Such factors included pigmentation/vascularity, surface texture,
      surface area, thickness (scar height), and pliability. RESULTS: Few studies have
      assessed scars; each provided an assessment scale of their own. Each scale is
      compared on the basis of accuracy, reliability, convenience in terms of
      feasibility and price. CONCLUSIONS: There remains still no ideal objective
      measurement out there despite promise seen in subjective evaluation. Method
      refinement will however accelerate our knowledge and interventions - based on
      increasing study power with enhanced metrics.

PMID- 19152572
TI  - Cutaneous bioengineering instrumentation standardization: the Tissue Viability
      Imager.
AB  - BACKGROUND: Tissue Viability Imaging (TiVi) is a new bioengineering technology
      intended for remote two-dimensional mapping of skin red blood cell concentration
      (RBC(conc)). Before use in the laboratory, work-site and dermatology clinic,
      critical performance parameters of this emerging technology require careful
      evaluation. OBJECTIVE: To assess short- and long-term stability, image
      uniformity, distance and image size dependence, ambient light and curvature
      influence in a production batch of Tissue Viability Imagers. METHODS: Four Tissue
      Viability Imagers from the same production batch were evaluated at two
      laboratories (one industrial and one dermatological) with respect to critical
      parameter performance. RESULTS: The average systematic drift in sensitivity over
      time was 0.27% and <1.02% for all four units tested. Difference in sensitivity
      between units was limited to 4.1% and was due to offset rather than gain
      deviation. Spatial variation in image uniformity was below 3.08% and 1.93% in the
      corners and centre of an individual image, respectively. This spatial variation
      could be further reduced to 0.25% and 0.13%, respectively by image normalization.
      Ambient light from a 40 W bulb or a 11 W fluorescent light source at a distance
      of 50-60 cm above the object, reduced the recorded values by about 10%, while the
      camera to object distance and image size had no detectable influence on
      sensitivity. Curved objects, such as human forearm, demonstrated an edge effect
      limited to below 10%. CONCLUSION: The critical TiVi performance parameters
      evaluated proved stable in relation to expected variations in skin RBC(conc) over
      time. Calibration by way of a two-point method may reduce differences in
      sensitivity between instruments to further facilitate inter-laboratory comparison
      of results.

PMID- 19152573
TI  - Tissue viability imaging: mapping skin erythema.
AB  - BACKGROUND: Tissue Viability Imaging (TiVi) is an emerging bioengineering
      technology intended for two-dimensional mapping of skin erythema and blanching.
      Before TiVi can be effectively used in studies of diseased or damaged skin, the
      variability in normal skin red blood cell concentration (RBC(conc)) requires
      evaluation. OBJECTIVE: To demonstrate how TiVi maps spatial and temporal
      variations in normal skin RBC(conc) at the dorsal side of the hand at rest and
      during post-occlusive hyperemia. METHODS: Short-term and day-to-day variations in
      skin RBC(conc) were quantified at the dorsal side of the hand in four healthy
      volunteers at rest. In a separate study, the increase in skin RBC(conc) was
      recorded during post-occlusive hyperemia. RESULTS: A lower skin RBC(conc) (179
      184 TiVi units) was observed at the back of the hand and base of the thumb
      compared with areas adjacent to the nailfoldfold region of the fingers (190-213
      TiVi units). The short-term variation (within 70 s) was <2% in all areas of the
      dorsal side of the hand, while day-to-day variations were in the range 5-7% in
      the back of the hand and up to 10% in areas adjacent to the nailfold region. In
      the post-occlusive hyperemia phase, up to a 60% increase in skin RBC(conc) was
      observed in the early part of the reactive hyperemia phase. This increase in skin
      RBC(conc) successively decreased but remained about 18% above the pre-occlusion
      level after 30 min. CONCLUSION: Establishment of healthy skin RBC(conc) reference
      values is important for the design of versatile test procedures for assessment of
      skin damage caused by vibration tools, chemical exposure or peripheral vascular
      disease.

PMID- 19152574
TI  - Comparison of tissue viability imaging and colorimetry: skin blanching.
AB  - BACKGROUND: Operator-independent assessment of skin blanching is important in the
      development and evaluation of topically applied steroids. Spectroscopic
      instruments based on hand-held probes, however, include elements of operator
      dependence such as difference in applied pressure and probe misalignment, while
      laser Doppler-based methods are better suited for demonstration of skin
      vasodilatation than for vasoconstriction. OBJECTIVE: To demonstrate the potential
      of the emerging technology of Tissue Viability Imaging (TiVi) in the objective
      and operator-independent assessment of skin blanching. METHODS: The WheelsBridge
      TiVi600 Tissue Viability Imager was used for quantification of human skin
      blanching with the Minolta chromameter CR 200 as an independent colorimeter
      reference method. Desoximetasone gel 0.05% was applied topically on the volar
      side of the forearm under occlusion for 6 h in four healthy adults. In a separate
      study, the induction of blanching in the occlusion phase was mapped using a
      transparent occlusion cover. RESULTS: The relative uncertainty in the blanching
      estimate produced by the Tissue Viability Imager was about 5% and similar to that
      of the chromameter operated by a single user and taking the a(*) parameter as a
      measure of blanching. Estimation of skin blanching could also be performed in the
      presence of a transient paradoxical erythema, using the integrated TiVi software.
      The successive induction of skin blanching during the occlusion phase could
      readily be mapped by the Tissue Viability Imager. CONCLUSION: TiVi seems to be
      suitable for operator-independent and remote mapping of human skin blanching,
      eliminating the main disadvantages of methods based on hand-held probes.

PMID- 19152575
TI  - Use of digital photography and image analysis techniques to quantify erythema in
      health care workers.
AB  - BACKGROUND/AIMS: Nosocomial infections affect up to 26% of ICU patients.
      Compliance with the required hand hygiene procedures remains low, rarely
      exceeding 50%, with skin irritation as one of the main reasons for lack of
      conformity. The aim was to quantify the epidermal barrier effects, particularly
      erythema, from repetitive exposure to hand hygiene procedures among health care
      workers (HCWs) using an objective, reliable clinical method that could evaluate
      the entire hand surface. METHODS: The hand skin of HCWs was evaluated before the
      initial scrub and at the end of multiple 2-3 days work cycles during spring
      (n=54) and winter (n=60) trials. The skin condition was measured with live visual
      skin evaluation (LSG), digital image analysis (DIA) of high-resolution digital
      images, and visual perception evaluation (VPS) of image pairs. RESULTS: The HCWs
      had significantly higher values of erythema than the non-HCW control group with
      all methods. Knuckle erythema increased over the cycle in both seasons. It
      decreased during recovery in spring and continued to increase during recovery in
      winter. For the DIA area of excess redness, the quantitative measure of erythema,
      the decrease over the cycle in spring was significantly different than the
      increase over the cycle in winter. Minimal changes in area of excess redness
      occurred during recovery in both seasons. With the VPS, both judges found a
      decrease in erythema during recovery in spring and an increase during recovery in
      winter, indicating significant differences for spring vs. winter (P<0.05). No
      differences in VPS erythema were seen for either product set over the work cycle
      during spring. Correlations were observed for (1) results for the VPS vs. the LSG
      method and (2) between excess erythema (mu+sigma) from DIA and the VPS erythema
      scores. Relatively low correlations were found between the DIA and VPS methods,
      i.e., knuckle mu+sigma and VPS erythema. CONCLUSIONS: Significant work cycle
      effects for spring vs. winter were observed with DIA, while significant effects
      were found during the recovery period with VPS. DIA produced an objective
      quantitative measure of erythema that was not limited or influenced by other
      aspects of skin irritation (e.g., dryness, scaling) or texture encountered in the
      visual methods of LSG and VPS. The DIA method minimizes the difficulty in
      differentiating erythema severity. Standardization of image capture and
      processing allows assessment of skin condition across clinical locations. The VPS
      is a more reliable way to compare skin condition at different times, i.e.
      beginning vs. the end of a treatment cycle, because images are viewed
      simultaneously and can be carefully examined for differences.

PMID- 19152576
TI  - A multitechnique evaluation of topical corticosteroid treatment.
AB  - BACKGROUND/PURPOSE: Corticosteroids are widely prescribed for systemic or local
      treatment of inflammatory autoimmune disorders. Long-term therapy is associated
      with side effects and causes cutaneous atrophy of the epidermis and the dermis.
      The present study aims to evaluate with several noninvasive techniques, the skin
      modifications observed during corticosteroids treatment. The potential of skin
      mechanical measurement and ultrasound radio frequency (RF) signal analysis are
      proposed as new measures more closely related to the functional impairments.
      METHODS: Thirteen young healthy women volunteers had two applications per day on
      one arm of topical Clobetasol propionate 0.05% for 28 days, and they were
      followed for 28 days more. Skin modifications were studied by high-frequency
      ultrasound imaging, ultrasound RF signal analysis, optical coherence tomography
      and by the suction test. RESULTS: For all the techniques, a statistically
      significant change is observed with treatment. Large variations, around 30%, are
      observed for all techniques, but less for ultrasound imaging (10%). Dermis and
      epidermis thickness presented stable measurements on the nontreated zone. At the
      end of the study, measures returned to normal. The dynamic is mainly observed
      within the first 14 days of treatment and within the first 14 days after its
      cessation. CONCLUSION: Similar dynamics of skin modification during
      corticosteroid treatment was observed with very different techniques. Moreover,
      the potential of RF ultrasound analysis and mechanical skin measurement for
      characterizing skin structural and functional impairments has been evaluated.

PMID- 19152577
TI  - In vivo confocal laser scanning microscopy for non-invasive diagnosis of
      pemphigus foliaceus.
AB  - BACKGROUND/PURPOSE: In vivo confocal laser scanning microscopy (CLSM) is a modern
      non-invasive method for investigation of the skin that allows real-time
      visualization of individual cells and sub-cellular structures at resolution
      similar to the one provided by routine histopathology. Our aim was to investigate
      the potential of CLSM for non-invasive diagnosis of pemphigus foliaceus (PF).
      METHODS: Pre-existing and mechanically induced lesions in two cases of PF were
      examined by means of CLSM, parallel to routine histology, direct
      immunofluorescence microscopy and enzyme-linked immunosorbent assay performed in
      the same patients. RESULTS: The morphological features characteristic for PF,
      namely an intraepidermal blister with acantholytic cells in the blister cavity,
      were readily detectable by means of CLSM. The findings were consistent in both
      patients and across the investigated lesions. The confocal images were consistent
      with the routine histology of the pre-existing lesions. No differences in the
      confocal images of pre-existing lesions compared with mechanically induced ones
      were observed. CONCLUSIONS: Our findings suggest the potential of CLSM as a non
      invasive tool for the diagnosis of pemphigus and differentiation of its subtype.
      Although at present the method cannot replace the current diagnostic standards
      for pemphigus, it may be successfully used as in vivo non-invasive screening tool
      to facilitate the diagnosis and point to the need for further investigation of
      the patient.

PMID- 19152578
TI  - Quantitative magnetic resonance imaging of subcutaneous adipose tissue.
AB  - BACKGROUND/PURPOSE: Quantitative transverse relaxation time (T(2)) magnetic
      resonance (MR) imaging has been used with the aim to characterize subcutaneous
      adipose tissue. Protons in adipose tissue have a fast exchange behavior giving bi
      component transverse relaxation processes with short and long relaxation time
      values depending on the tissue properties. METHODS: MR images were acquired on a
      1 T Siemens MR scan using a multi-spin-echo sequence. A high sensitive surface
      coil, enabling low noise MR images with voxel size of 10 mm(3), was used for
      performing accurate quantitative T(2) imaging. These acquisition parameters were
      determined by a preliminary study performed on an oil phantom known to be a
      valuable model for mimicking in vivo adipose tissue. In vivo study of the thigh
      adipose tissue was carried out on 30 volunteers. 20 women with various clinically
      diagnosed cellulite grades and 10 males, among them five showed overweight.
      Tissue characterization was finally performed through the analysis of the T(2)
      distributions. RESULTS: Phantom study showed that improvements in the precision
      in T(2) measurement are obtained at the expense of the spatial resolution.
      Uncertainties in T(2) measurements are three times lower by considering a region
      of interest of 3 x 3 pixels compared with a pixel by pixel analysis. The in vivo
      study showed that women groups present higher mean short T(2S) component values
      than men. Histogram of T(2) distribution showed that the maximum amplitude is
      observed at a lower value for the overweight men group. In addition, larger
      values around the septae were visualized on the long relaxation time images.
      CONCLUSIONS: This study shows that precise T(2) map of adipose tissue can be
      computed. The balance between precision and spatial resolution is examined.
      Preliminary results relative to tissue organization and to difference between
      clinical groups proves the potential of the quantitative MRI.

PMID- 19152579
TI  - Comparison of closed chamber and open chamber evaporimetry.
AB  - BACKGROUND: Recently it has been asserted that a closed chamber evaporimeter, the
      VapoMeter, offers advantages over standard open chamber devices in measuring
      transepidermal water loss (TEWL). Purported improvements include the ability to
      take measurements at any angle, short reading times and insensitivity to external
      air currents. These claims are compelling, considering that measuring TEWL at
      diverse skin sites can be tedious, especially with children. The primary aim of
      this study was to compare the performance of closed and open chamber instruments
      when they were held at various angles and, secondly to evaluate the ability of
      the devices to discriminate between test conditions. METHODS: The performance of
      closed chamber (VapoMeter) and open chamber (DermaLab) evaporimeters were
      compared by measuring water vapor emitted from IMS Vitro-skin that had been
      hydrated to a predetermined level. Measurements were taken at three angles from
      vertical - 0 degrees, 45 degrees, and 90 degrees. Vitro-skin samples were weighed
      periodically throughout the experimental phase to verify water loss rates.
      RESULTS: Both the VapoMeter and the DermaLab yielded significantly lower water
      loss values when held at angles that varied from the vertical (0 degrees)
      position, indicating that the closed chamber device is no more capable of
      accurately measuring TEWL at any angle than an open chamber instrument. The
      DermaLab provided better discrimination than the VapoMeter when the instruments
      were held vertically, as is the only prescribed testing position for open-chamber
      instruments. The VapoMeter was easier to use than the DermaLab; however, there
      was evidence that the sealed chamber could become saturated under high water loss
      conditions. CONCLUSIONS: Previous assertions that the VapoMeter closed chamber
      evaporimeter is capable of measuring TEWL regardless of angle were not validated.
      Each device appeared capable of accurately estimating water loss rates only in
      the vertical position. Although the VapoMeter was easier to use than the open
      chamber device, its tendency to become saturated under high water loss conditions
      could be a disadvantage when assessing dynamic TEWL.

PMID- 19152580
TI  - Dynamic indentation on human skin in vivo: ageing effects.
AB  - BACKGROUND/PURPOSE: Knowledge of the mechanical properties of the human skin is
      very important for cosmetic and clinical research. Objective and quantitative
      measurements are essential to compare studies performed by different
      experimenters in different centres. The aim of this paper is to present a method
      to measure the viscoelastic properties of human skin in vivo using dynamic
      indentation. METHODS: A complete device to assess the stiffness and damping of
      skin has been developed. The frequency and strain amplitude range from 10 to 60
      Hz and from 1 to 10 mum. Tests on pure elastic inert materials have been
      performed to validate the device. An in vivo study including dynamic indentation,
      suction test, hydration measurement and topographic analysis has been performed
      on 46 subjects aged from 18 to 70 years, divided into three groups. RESULTS:
      Results on inert materials show the validity of the device developed. The
      mechanical behaviour of the skin can be described by a Kelvin-Voight model under
      dynamic indentation. A comparison with a suction test, hydration and topographic
      measurements shows that the stiffness and the damping measured by dynamic
      indentation correspond mainly to the natural tense state of the skin on the body
      due to the dermis. A weak correlation has been found between dynamic indentation
      and suction parameters. The complex modulus measured by dynamic indentation at 10
      Hz frequency stress ranges from 7.2 +/- 2.1 kPa for the oldest group to 10.7 +/-
      2.6 kPa for the youngest group. CONCLUSION: The device presented gives convincing
      results. The measurement of stiffness and damping complements the viscoelastic
      phenomenological parameters of the suction test.

PMID- 19152581
TI  - Characterization of the mechanical properties of a dermal equivalent compared
      with human skin in vivo by indentation and static friction tests.
AB  - BACKGROUND/AIMS: The study of changes in skin structure with age is becoming all
      the more important with the increase in life. The atrophy that occurs during
      aging is accompanied by more profound changes, with a loss of organization within
      the elastic collagen network and alterations in the basal elements. The aim of
      this study is to present a method to determine the mechanical properties of total
      human skin in vivo compared with dermal equivalents (DEs) using indentation and
      static friction tests. METHODS: A new bio-tribometer working at a low contact
      pressure for the characterization the mechanical properties of the skin has been
      developed. This device, based on indentation and static friction tests, also
      allows to characterize the skin in vivo and reconstructed DEs in a wide range of
      light contact forces, stress and strain. RESULTS: This original bio-tribometer
      shows the ability to assess the skin elasticity and friction force in a wide
      range of light normal load (0.5-2 g) and low contact pressure (0.5-2 kPa). The
      results obtained by this approach show identical values of the Young's modulus
      E(*) and the shear modulus G(*) of six DEs obtained from a 62-year-old subject
      (E(*)=8.5+/-1.74 kPa and G(*)=3.3+/-0.46 kPa) and in vivo total skin of 20
      subjects aged 55 to 70 years (E(*)=8.3+/-2.1 kPa, G(*)=2.8+/-0.8 kpa).

PMID- 19152582
TI  - Assessment of moisturizers and barrier function restoration using dynamic
      methods.
AB  - BACKGROUND/PURPOSE: Dynamic methods, such as the mathematical modelling of the
      transepidermal water loss curves that result from a plastic occlusion stress test
      (POST), enable the complete characterization of the dynamic water balance
      established between the deep and the superficial skin structures. Previous
      studies have indicated that this methodology was able to detect impaired barrier
      function and differentiate normal and dry skin. The objective of the present
      study is to apply the discriminative capacity of the model to the efficacy
      testing of moisturizing products. METHODS: A moisturizing cream containing urea
      was applied for 2 weeks to the lower leg of volunteers with dry skin. After this
      period, a POST was performed in the treated and control untreated site and a
      mathematical model was adjusted to the resulting desorption curves. RESULTS:
      Results indicate that, after treatment of the skin with the cream for 2 weeks,
      statistically different kinetic parameters are obtained in the treated site,
      which suggests an improvement in the water dynamic balance and skin barrier. The
      data generated by this study was compared with that obtained in a similar
      investigation that was performed a year earlier. Analysis of the dispersion of
      results indicates that the method has good reproducibility. CONCLUSIONS: These
      findings confirm that the method has enough sensitivity to assess in vivo the
      effect of moisturizers on human skin, and also that this evaluation can be
      performed in a shorter period than that required by the regression method. This
      methodology can also be considered more informative, because the analysis of the
      different parameters obtained by the model is indicative of the mechanism of
      action of the product applied to the skin.

PMID- 19152583
TI  - Abstracts of the 1st Joint World Congress of the International Society for
      Biophysics and Imaging of the Skin (ISBS) and the International Society for
      Digital Imaging of the Skin (ISDIS). May 7-10, 2008. Seoul, Korea.

PMID- 19152584
TI  - Evidence-based veterinary dermatology: a systematic review of interventions for
      Malassezia dermatitis in dogs.
AB  - The aim of this systematic review was to evaluate the efficacy of antifungal
      treatments for Malassezia dermatitis in dogs and, when possible, to propose
      recommendation for or against their use. Electronic searches were carried out
      using PubMed MEDLINE(R), CABDirect and CONSULTANT database. The volumes of
      Advances in Veterinary Dermatology, the proceedings of ESVD/ECVD and AAVD/ACVD
      congresses were hand-searched for studies relevant to this review. All articles
      and book chapters discussing treatment of Malassezia dermatitis were scanned for
      additional citations. Lastly, a request was sent to the Vetderm Listserv to share
      recent clinical trials. The analysis evaluated study design, methodology quality,
      subject enrolment quality, type of interventions and outcome measures. The
      searches identified 35 articles, and 14 trials that fulfilled the following
      selection criteria: (i) in vivo clinical trials, (ii) dogs showing clinical
      lesions of Malassezia dermatitis and (iii) enrolment of at least five dogs. Among
      these, only eight studies fulfilled the following additional criterion: (iv)
      prospective in vivo clinical trials reporting clinical and mycological outcome
      measures. A total number of 14 different treatment protocols included four
      blinded, randomized and controlled trials (quality of evidence grade A), four
      controlled studies lacking blinding and/or randomization (grade B), five open
      uncontrolled trials (grade C) and one descriptive study (grade D). This
      systematic review allowed us to recommend, with good evidence, the use of only
      one topical treatment of Malassezia dermatitis (2% miconazole nitrate +2%
      chlorhexidine, twice a week for 3 weeks) and with fair evidence the use of two
      systemic treatments with azole derivatives (ketoconazole, 10 mg kg(-1) day(-1)
      and itraconazole, 5 mg kg(-1) day(-1) for 3 weeks).

PMID- 19152585
TI  - Clinical, histopathological and epidemiological study of canine straelensiosis in
      the Iberian Peninsula (2003-2007).
AB  - Straelensiosis is a relatively new disease described in dogs and produced by a
      trombiculid larva known as Straelensia cynotis. Few cases have been reported in
      the English literature. Straelensiosis has been observed in Southern France and
      Northern Portugal causing a distinctive nodular dermatitis. The present study
      describes the clinical, histopathological and epidemiological features of 19
      cases diagnosed as straelensiosis in the north of Spain and Portugal (2003-2007).
      A follow-up of the animals after diagnosis was carried out. Differences with
      previously described cases were observed, especially concerning epidemiology and
      histopathology. The grade of response to different treatments and new microscopic
      features are discussed. The study concludes that S. cynotis can cause a nodular
      dermatitis in rural and hunting dogs in Spain and Portugal and is associated with
      particular seasonal and geographical factors.

PMID- 19152586
TI  - Investigations on the nature and pathogenicity of circulating antikeratinocyte
      antibodies in dogs with pemphigus foliaceus.
AB  - In humans with pemphigus foliaceus (PF), pathogenic autoantibodies are
      principally of IgG4 subclass and they cause superficial vesiculation when
      injected into neonatal mice. The objectives of this study were to determine the
      isotypes of circulating antikeratinocyte antibodies in dogs with PF, to assess
      whether serum antikeratinocyte antibody titres decreased during successful
      treatment, and to study whether such antibodies were pathogenic in passive
      transfers. Using indirect immunofluorescence with neonatal mouse skin substrates,
      circulating antikeratinocyte IgG antibodies were detected in 36 of 44 dogs with
      PF (82%). Serum autoantibodies belonged predominantly to IgG4 (three of 44; 80%)
      and IgG1 (30 of 44; 68%) subclasses. Antikeratinocyte IgG antibodies were
      detected in 16 of 20 normal dogs (80%), and these antibodies were IgG1 (16 of 20,
      80%) but rarely IgG4 (two of 20; 10%) isotypes. In four dogs, IgG4
      antikeratinocyte antibody titres decreased concomitantly to lesions nearing or
      reaching complete remission. In contrast, IgG or IgG1 titres remained stable or
      increased when lesions abated. Antikeratinocyte antibodies targeted mainly
      intercellular autoantigen(s) in the stratum granulosum, while in fewer dogs, such
      antibodies bound to cytoplasmic basal antigen(s). Intradermal injections of PF or
      pemphigus vulgaris (PV) IgG into neonatal mice caused subgranular or suprabasal
      acantholytic vesiculation without granulocyte infiltration, respectively. Similar
      transfers of normal dog IgG did not cause vesiculation. These observations
      suggest that antikeratinocyte IgG4 antibodies could be relevant to disease
      pathogenesis. Importantly, canine PF or PV IgG appear to be pathogenic when
      transferred passively into mice, causing vesiculation at epidermal levels similar
      to those of the natural disease.

PMID- 19152587
TI  - Plasma and ear tissue concentrations of enrofloxacin and its metabolite
      ciprofloxacin in dogs with chronic end-stage otitis externa after intravenous
      administration of enrofloxacin.
AB  - The purpose of this study was to measure the concentrations of enrofloxacin and
      its metabolite ciprofloxacin following intravenous administration of enrofloxacin
      in the plasma and ear tissue of dogs with chronic end-stage otitis undergoing a
      total ear canal ablation and lateral bulla osteotomy. The goals were to determine
      the relationship between the dose of enrofloxacin and the concentrations of
      enrofloxacin and ciprofloxacin, and determine appropriate doses of enrofloxacin
      for treatment of chronic otitis externa and media. Thirty dogs were randomized to
      an enrofloxacin-treatment group (5, 10, 15 or 20 mg kg(-1)) or control group (no
      enrofloxacin). After surgical removal, ear tissue samples (skin, vertical ear
      canal, horizontal ear canal, middle ear) and a blood sample were collected.
      Concentrations of enrofloxacin and ciprofloxacin in the plasma and ear tissue
      were measured by high performance liquid chromatography. Repeated measures models
      were applied to log-transformed data to assess dosing trends and Pearson
      correlations were calculated to assess concentration associations. Ear tissue
      concentrations of enrofloxacin and ciprofloxacin were significantly (P < 0.05)
      higher than plasma concentrations. Each 5 mg kg(-1 )increase in the dose of
      enrofloxacin resulted in a 72% and 37% increase in enrofloxacin and ciprofloxacin
      concentrations, respectively. For bacteria with an minimal inhibitory
      concentration of 0.12-0.15 or less, 0.19-0.24, 0.31-0.39 and 0.51-0.64 microg mL(
      1), enrofloxacin should be dosed at 5, 10, 15 and 20 mg kg(-1), respectively.
      Treatment with enrofloxacin would not be recommended for a bacterial organism
      intermediate or resistant in susceptibility to enrofloxacin since appropriate
      levels of enrofloxacin would not be attained.

PMID- 19152588
TI  - The ABCB1-1Delta mutation is not responsible for subchronic neurotoxicity seen in
      dogs of non-collie breeds following macrocyclic lactone treatment for generalized
      demodicosis.
AB  - P-glycoprotein (P-gp), encoded by the multiple drug resistance gene ABCB1 (also
      known as MDR1), is an integral component of the blood brain barrier crucial in
      limiting drug uptake into the central nervous system. Altered expression or
      function of P-gp, as seen in dogs of the collie lineage homozygous for the
      nt228(del4) mutation of the ABCB1 gene (ABCB1-1Delta), can result in potentially
      fatal neurotoxicosis, especially following administration of systemic macrocyclic
      lactones (SML). Occasionally, dogs from unrelated breeds develop subchronic signs
      of neurotoxicity when receiving SML to treat generalized demodicosis. It is
      possible that these dogs are heterozygous carriers of the ABCB1-1Delta mutation,
      resulting in decreased P-gp activity and central neurotoxicosis. Cheek swabs were
      collected from 28 dogs with generalized demodicosis that had shown subchronic
      signs of neurotoxicity following daily oral administration of ivermectin or other
      SML. Ten of these animals received concurrent systemic treatment with other
      confirmed or putative P-gp substrates. After DNA extraction, the relevant portion
      of the ABCB1 gene was amplified by polymerase chain reaction, and sequenced.
      Twenty-seven dogs were homozygous normal while one dog was heterozygous for the
      ABCB1-1Delta mutation. Therefore, with the exception of one dog, the observed
      neurotoxicity could not be attributed to the ABCB1-1Delta mutation. Possible
      explanations for the adverse reactions observed include pharmacological
      interactions (administration of SML with other P-gp substrates or inhibitors),
      excessively high doses, polymorphisms in P-gp expression, uncharacterized
      mutations in the ABCB1 gene or in another gene, or phenomena unrelated to the SML
      P-gp interaction.

PMID- 19152589
TI  - Successful treatment of sebaceous adenitis in a rabbit with ciclosporin and
      triglycerides.
AB  - A 4-year-old rabbit was presented with a chronic exfoliative dermatitis and
      patchy alopecia. General physical examination revealed no abnormalities. Skin
      scrapings and fungal culture were negative. A blood sample was obtained for a
      complete blood cell count and biochemical profile, and yielded results that were
      within normal limits. Radiographic examination of the thorax excluded the
      presence of a thymoma. Histopathology of the skin showed orthokeratotic
      hyperkeratosis, absence of sebaceous glands and mural lymphocytic folliculitis,
      consistent with sebaceous adenitis. Oral treatment was started with ciclosporin
      dissolved in a medium-chain triglyceride solution (Miglyol 812), combined with
      essential fatty acids and topical propylene glycol sprays. Within 2 months of
      treatment, complete regression of skin lesions and regrowth of hair was observed.
      Serum chemistry values including kidney and liver function tests remained within
      reference range during the course of treatment. Histopathological examination of
      control biopsies of the skin showed presence of normal sebaceous glands and
      active hair follicles. Treatment was changed to a different pharmaceutical
      formulation of ciclosporin without Miglyol and deterioration of clinical signs
      was noticed. Using pure Miglyol 812, however, resulted in a gradual improvement
      of 60%. A nearly complete response was again observed after re-administration of
      the combination ciclosporin/Miglyol. It is hypothesized that sebaceous adenitis
      in the rabbit is most likely due to an autoimmune reaction directed at the
      sebaceous glands and a defect in lipid metabolism. The outcome indicates that a
      combination of ciclosporin and Miglyol 812 is a promising new treatment for
      sebaceous adenitis in rabbits.

PMID- 19152590
TI  - Superficial necrolytic dermatitis associated with extrapancreatic glucagonoma in
      a dog.
AB  - An 11-year-old Shih Tzu presented with crusting and erythema, mainly on the
      abdomen and the root of the tail. Based on histopathological findings, blood
      examinations and necropsy findings, the condition was diagnosed as superficial
      necrolytic dermatitis associated with a glucagon-secreting extrapancreatic
      neuroendocrine tumour. Gross necropsy revealed tumour invasion into the spleen,
      liver, adrenal glands and mesenteric lymph nodes. Immunohistochemical analysis of
      the neoplastic cells revealed that the tumour was a glucagonoma, consistent with
      earlier findings of persistent glucagonaemia and hypoaminoacidaemia.

PMID- 19152591
TI  - Breed predisposition to congenital alacrima in dogs.
AB  - OBJECTIVE: To evaluate the clinical characteristics and breed predisposition of
      congenital alacrima in dogs. Animals studied Dogs with congenital
      keratoconjunctivitis sicca. PROCEDURES: A search of the medical records of the
      University of Tennessee Veterinary Teaching Hospital from 1974-2005 and the
      University of California-Davis Veterinary Teaching Hospital from 1986-2006 for
      dogs under 1 year of age with a diagnosis of keratoconjunctivitis sicca (KCS) was
      performed. These cases were further reviewed for dogs with a Schirmer's tear test
      I of <or= 5 mm/min before 6 months of age, with no known causes for KCS, which
      did not respond to appropriate KCS therapy; these cases were considered to have
      congenital alacrima. These breeds were compared to all other breeds using the
      Fisher's exact test with correction for multiple comparisons. RESULTS: Congenital
      alacrima was identified in 19 dogs representing 11 breeds and mixed breeds.
      Yorkshire Terriers and Bedlington Terriers were statistically overrepresented
      compared to reference populations (P < 0.01 and P = 0.04, respectively).
      CONCLUSIONS: Yorkshire terriers are significantly at risk for congenital alacrima
      compared to other breeds. The significance of the increase in congenital alacrima
      in Bedlington Terriers in this study may not be clinically relevant and may be
      due to the small total number of dogs of this breed that presented to the both
      hospitals. Based on the poor response to therapy in humans with congenital
      alacrima, it may be prudent to offer guarded prognoses for KCS in juvenile
      Yorkshire terriers.

PMID- 19152592
TI  - Corneal stromal invasive squamous cell carcinoma: a retrospective morphological
      description in 10 horses.
AB  - OBJECTIVE: To describe the pathomorphological features of corneal stromal
      invasive squamous cell carcinoma (CSI-SCC) in horses. MATERIAL AND METHODS: A
      total of 87 equine SCC in the Comparative Ocular Pathology Laboratory of
      Wisconsin database were retrieved. The signalment and anatomical distribution
      were summarized. Ten CSI-SCC out of 87 SCCs were further investigated focusing on
      pathomorphological description. All 10 cases were stained with H&E, periodic acid
      Schiff stain and Verhoeff's elastic stain. RESULTS: Four Appaloosas, two Quarter
      horses, two American Paint, one Pinto and one Thoroughbred horse were affected.
      The mean age at the time of enucleation/keratectomy was 16.7 +/- 5.2 years. Out
      of 10, five horses were clinically diagnosed as chronic stromal keratitis, 3 of
      10 had a previous biopsy diagnosed as SCC, 1 of 10 was described as stromal mass,
      and 1 of 10 as invasive SCC. Previous keratectomies before enucleation were
      performed in 3 of 10 horses, of which 2 also had additional
      lasertherapy/cryotherapy. Seven of 10 cases showed tumor infiltration in the
      anterior-mid stroma, 3/10 in the mid-deep stroma. The anterior epithelium had no
      contact with the CSI-SCC in 8 of 10 cases, 7 of 10 had intact and normal
      epithelium, and 3 of 10 showed intact, dysplastic corneal and conjunctival
      epithelium. The limbus was not pigmented in 8 of 10 specimens. There was a mild
      moderate lymphoplasmacytic inflammation between the neoplastic islands. Solar
      elastosis was present in 2 of 10 samples. CONCLUSION: The CSI-SCC shows a
      distinctive intrastromal tumor growth pattern with a smooth, intact corneal
      epithelium. The tumor can be underestimated and misdiagnosed as chronic active
      stromal keratitis. A deep biopsy is necessary for the definitive diagnosis.

PMID- 19152593
TI  - Comparison of capsular opacification and refractive status after placement of
      three different intraocular lens implants following phacoemulsification and
      aspiration of cataracts in dogs.
AB  - OBJECTIVE: To evaluate the effect of lens design and biomaterial on formation of
      posterior capsular opacification (PCO) and refractive correction. Animals studied
      Sixty dogs undergoing bilateral phacoemulsification for mature or diabetic
      cataracts. PROCEDURES: One randomly selected eye received a rounded edge 41D
      polymethyl-methacrylate (PMMA) intraocular replacement lens (IOL) and the
      contralateral eye received either a squared edge 41D hydrophilic acrylic IOL (n =
      35) or a squared edge 40D hydrophobic acrylic IOL (n = 25). At the (mean = 79
      day) reexamination period, PCO was graded using direct slit-lamp observation and
      by masked observer evaluation of digital images of the IOLs. Streak retinoscopy
      and B-mode ultrasound were performed at this period. RESULTS: The PCO score via
      direct slit-lamp was significantly lower for the hydrophilic acrylic IOL when
      compared to the PMMA IOL. Masked observer evaluation of digital images revealed
      that the acrylic IOLs had lower but generally not statistically significant PCO
      scores than the PMMA IOLs. Streak retinoscopy showed that the PMMA IOL was
      significantly closer to emmetropia (+0.44 D) when compared to either the
      hydrophilic acrylic (+0.96 D) or the hydrophobic acrylic (+1.2 D) IOLs. B-mode
      ultrasonography revealed the center of the hydrophilic acrylic IOL is 0.31 mm
      closer to the retina and the center of the hydrophobic acrylic IOL is 0.63 mm
      further from the retina when compared to the center of the PMMA to retina
      distance. CONCLUSIONS: Square edged foldable acrylic IOLs show a predisposition
      towards generating slightly less PCO than round edged PMMA IOLs in the early
      postoperative period, however, both acrylic IOLs had greater persistent hyperopia
      than the PMMA IOLs.

PMID- 19152594
TI  - Relationship of the iridocorneal angle, as measured using ultrasound
      biomicroscopy, with post-operative increases in intraocular pressure post
      phacoemulsification in dogs.
AB  - OBJECTIVE: To investigate the relationship of the iridocorneal angle as it
      appears on ultrasound biomicroscopy (UBM) to increases in IOP post
      phacoemulsification in the canine eye. Animals studied 47 eyes of 28 dogs of
      various age, sex, and breed. METHODS: The ciliary process and limbus were used as
      a reference points to measure the angle opening distance (AOD), which was set by
      multiplying 0.45 by the distance between the ciliary process and limbus (when
      measured from the ciliary process). Pressure measurements were taken at five set
      points: Before, immediately post-, one day post-, 1 week post-, and 1 month post
      phacoemulsification. RESULTS: A weak relationship between the AOD and the IOP one
      day post-phacoemulsification (Intercept: 2.83, Slope: -1.24, P-value: 0.0155) was
      observed. No relationship immediately post-operative (Intercept: 3.45, Slope: 
      1.34, P-value: 0.0651), 1 week post-phacoemulsification (Intercept: 2.31, Slope: 
      0.01, P-value: 0.9829), 1 month post-phacoemulsification (Intercept: 1.85, Slope:
      -0.49, P-value: 0.1533) was observed. The pre-operative measurements made with
      UBM were: Distance from limbus to ciliary process (DLCP): (Minimum: 1.152,
      Maximum: 2.992, Mean: 1.91, SD: 0.468); AOD (Minimum: 0.104, Maximum: 0.764,
      Mean: 0.40, SD: 0.172). CONCLUSIONS: The relationship between AOD as measured by
      UBM pre-operatively is weakly associated with IOP pressure elevations at day one
      post-phacoemulsification. Further study is required prospectively to establish
      the importance of this relationship. Initial measurements of the canine
      iridocorneal angle were created, suggesting a method to be used in the future to
      establish true canine normal measurements.

PMID- 19152595
TI  - Anti-inflammatory effects of topical supernatant from human amniotic membrane
      cell culture on canine deep corneal ulcer after human amniotic membrane
      transplantation.
AB  - The objective of this study was to examine the effect of topically applied human
      amniotic epithelial cell (HAEC) culture supernatant on corneal inflammatory
      reaction in dogs. Twenty-five dogs were randomly assigned into five groups. The
      control group consisted of five dogs with normal cornea. Inductions of corneal
      ulcers were performed using 0.45 cm trephine and human amniotic membrane was
      transplanted in 20 dogs. These 20 dogs were assigned into four treatment groups:
      topical antibiotic, topical corticosteroid, topical mock media and topical
      culture supernatant from HAEC, respectively. Administrations of the testing
      agents started at 24 h (h) after transplantation four times daily for nine
      consecutive days. Tears were collected before an operation 24 h after
      transplantation, but before application of the testing agents on consecutive odd
      days following transplantation. The concentrations of interleukin-1beta (IL
      1beta) and nitric oxide (NO) in tear fluid were measured using canine IL-1beta
      ELISA kit and Griess assay, respectively. Our analysis indicates that elevations
      of IL-1beta and NO concentrations are associated with inflammatory conditions in
      the eyes. Corticosteroid, a reference anti-inflammatory drug, and the culture
      supernatant from HAEC significantly decreased IL-1beta and NO concentrations. In
      addition, the clinical signs such as conjunctivitis and neovascularization were
      decreased in both topical corticosteroid and supernatant from HAEC treated
      groups. Mock and antibiotic solutions failed to decrease NO and IL-1beta
      concentrations. In conclusion, topical application of the culture supernatant
      from HAEC alleviated inflammation in induced-corneal ulcer of dogs, possibly via
      inhibition of IL-1beta and NO production.

PMID- 19152596
TI  - Effect of bovine freeze-dried amniotic membrane (Amnisite-BA) on uncomplicated
      canine corneal erosion.
AB  - OBJECTIVE: To evaluate the effectiveness of bovine freeze-dried amniotic membrane
      (FD-AM) (Amnisite-BA) in the surgical treatment of corneal ulceration in dogs.
      ANIMALS STUDIED: Eight normal Shih-tzu dogs. PROCEDURES: The corneas of 16 eyes
      were scored with an 8.0-mm trephine under general anesthetic and 100% ethanol was
      applied to remove a standardized button of corneal epithelium. The eyes were
      treated as described below and the corneas were evaluated 48 h later. The dogs
      were divided into four treatment groups: (i) control, (ii) amniotic membrane
      transplantation (AMT), (iii) nictitating membrane flap and (iv) contact lens. The
      proportion of the corneal wound that healed was calculated and all eyes were
      enucleated. Histological sections of cornea were assessed with the proliferating
      cell nuclear antigen (PCNA) assay. RESULTS: The proportion of corneas healed in
      the different treatment groups was (i) 38.02%, (ii) 89.15%, (iii) 52.31%, and
      (iv) 60.56%. Epithelial healing was significantly increased in the AMT group (ii)
      (P = 0.001) while groups (iii) and (iv) were not significantly different from the
      control group (P = 0.537 and P = 0.198, respectively). The number of PCNA
      positive cells was (i) 275.00, (ii) 740.50, (iii) 285.75 and (iv) 420.59, these
      varying compared with the control group with statistical significance of (ii) P =
      0.002, (iii) P = 0.999, and (iv) P = 0.467. The greatest healing rate and
      epithelial cell proliferation was achieved with AMT compared to the other
      treatment regimes. CONCLUSIONS: The results of this study show that FD-AM
      transplantation is an effective treatment for enhancing canine corneal wound
      healing and suggest that the approach will provide superior results compared to
      conventional treatments for the condition.

PMID- 19152597
TI  - Hormographiella aspergillata keratomycosis in a dog.
AB  - A 4-year-old, female, Border Collie was presented to the University of Bern
      Veterinary Teaching Hospital, because of a corneal lesion of 10 days duration.
      The axial cornea presented a whitish fluorescein-positive plaque with irregular
      margins. A diagnosis of keratomycosis was made based on cytology. Medical therapy
      with local broad-spectrum antibiotic and fluconazole was instituted. After 1 week
      of treatment, the improvement was deemed unsatisfactory. Therefore, a lamellar
      keratectomy and conjunctival pedicle flap were performed. After surgery, the
      cornea healed uneventfully. Histology confirmed the diagnosis of keratomycosis.
      The fungus could not be grown in culture and a precise etiological diagnosis
      could only be obtained with genetic identification of the fungus. A PCR technique
      was used to amplify the fungal genome from the cornea. Hormographiella
      aspergillata, the asexual reproductive form of the basidiomycete Coprinopsis
      cinerea, was identified. As advised in human medicine, we encourage the use of
      this molecular technique to obtain an early species diagnosis, allowing targeted
      medical therapy.

PMID- 19152598
TI  - Aspergillus flavus keratomycosis in a cat treated with topical 1% voriconazole
      solution.
AB  - An 8-year-old male castrated Domestic Short-haired cat was examined for a 1-week
      history of blepharospasm and mucoid ocular discharge OS. Examination revealed
      ulcerative keratitis with stromal loss, stromal infiltrate, corneal edema,
      perilimbal vascularization and miosis. Cytology of the cornea revealed multiple
      dichotomously branching, septate fungal hyphae and severe, predominantly
      neutrophilic inflammation. PCR of the cytology samples confirmed the presence of
      Aspergillus flavus while fungal and bacterial cultures were negative. Treatment
      with topical 1% voriconazole solution was successful in resolving the
      keratomycosis.

PMID- 19152599
TI  - Conjunctival xanthoma in a blue and gold macaw (Ara ararauna).
AB  - A 17-year-old female blue and gold macaw (Ara ararauna) presented for evaluation
      of a discreet, conjunctival mass of the OD. No other abnormalities were found on
      ophthalmic or physical examination. A heterophilic leukocytosis was present on
      the complete blood count, and elevated aspartate aminotransferase activity,
      creatinine kinase activity and cholesterol were present on the plasma
      biochemistry panel. Surgical removal of the mass was complete and no recurrence
      has occurred by six months after excision. Reduction of dietary fats was
      recommended to reduce serum cholesterol levels and reduce the likelihood of
      future occurrence of xanthomas in this bird.

PMID- 19152600
TI  - Keratoconjunctivitis associated with Toxoplasma gondii in a dog.
AB  - A 12-year-old Pug presented with a 3-mm corneal mass OD. The dog was currently
      being treated for keratoconjunctivitis sicca (KCS) and pigmentary keratitis OU. A
      superficial keratectomy followed by cryotherapy was performed OD. A
      histopathologic diagnosis of epithelial dysplasia and suppurative keratitis was
      made and the lesion resolved. Two months later, a yellow/tan conjunctival mass,
      diffuse chemosis and conjunctival thickening was discovered OD. Necrotizing
      conjunctivitis with protozoal parasites was diagnosed with histopathology.
      Complete blood count and a serum biochemistry panel were normal. Neospora caninum
      and Toxoplasma gondii titers were negative. The conjunctivitis resolved after a 6
      week course of oral clindamycin. Two months later, the patient presented with a
      similar conjunctival mass OS. Toxoplasma gondii was confirmed as the etiologic
      agent with immunohistochemical staining. Repeat T. gondii titers were negative.
      Oral clindamycin was re-instituted. The corneal biopsy was re-reviewed and
      protozoal organisms were discovered. Three months later, a recurrence was
      suspected and oral ponazuril was initiated for 28 days. There has been no
      evidence of recurrence since this treatment. Ocular toxoplasmosis is rare in the
      dog but reports have included episcleritis, scleritis, retinitis, anterior
      uveitis, ciliary epithelium hyperplasia, optic neuritis and polymyositis. To our
      knowledge, this is the first confirmed report of toxoplasmosis causing only
      corneal and conjunctival disease in the dog. We hypothesize that these localized
      lesions may be associated with topical immunomodulating therapy for KCS.
      Toxoplasmosis should be considered as a differential for canine conjunctivitis
      and corneal disease and has the potential to manifest in one or both eyes.

PMID- 19152602
TI  - Current issues relating to the transfusion of stored red blood cells.
AB  - The development of blood storage systems allowed donation and transfusion to be
      separated in time and space. This separation has permitted the regionalization of
      donor services with subsequent economies of scale and improvements in the quality
      and availability of blood products. However, the availability of storage raises
      the question of how long blood products can and should be stored and how long
      they are safe and effective. The efficacy of red blood cells was originally
      measured as the increment in haematocrit and safety began with typing and the
      effort to reduce the risk of bacterial contamination. Appreciation of a growing
      list of storage lesions of red blood cells has developed with our increasing
      understanding of red blood cell physiology and our experience with red blood cell
      transfusion. However, other than frank haemolysis, rare episodes of bacterial
      contamination and overgrowth, the reduction of oxygen-carrying capacity
      associated with the failure of some transfused cells to circulate, and the
      toxicity of lysophospholipids released from membrane breakdown, storage-induced
      lesions have not had obvious correlations with safety or efficacy. The safety of
      red blood cell storage has also been approached in retrospective epidemiologic
      studies of transfused patients, but the results are frequently biased by the fact
      that sicker patients are transfused more often and blood banks do not issue blood
      products in a random order. Several large prospective studies of the safety of
      stored red blood cells are planned.

PMID- 19152603
TI  - Effect of Haemostatic Control Resuscitation on mortality in massively bleeding
      patients: a before and after study.
AB  - BACKGROUND AND OBJECTIVES: Evidence supporting the use of platelets and plasma in
      resuscitation of massive bleedings is questionable. Current consensus guidelines
      recommend restrictive use. Our aim was to determine the effect of changing the
      transfusion practice on 30-day survival in massively bleeding patients. MATERIALS
      AND METHODS: Consecutive adult patients receiving more than 10 units of red blood
      cells (RBC) within 24 h 2 years prior to (2002-2003) and 2 years after (2005
      2006) a change in transfusion practice were included. In 2004, we implemented
      Haemostatic Control Resuscitation (HCR) with preemptive use of platelets and
      plasma, administered in transfusion packages, comprising 5 units of RBCs, 5 units
      of fresh-frozen plasma and 2 units of platelet concentrates (PC), when massive
      bleeding occurred or upon arrival at the emergency room and thereafter directed
      by thrombelastography throughout the peri- and postoperative period. RESULTS: In
      2005-2006, the 442 patients received more PCs within 24 h from admission [mean
      5.0 (SD 4.2) vs. 1.7 (2.0); P < 0.0001] and had a smaller decrease in platelet
      count during the bleeding episode [91.5 (81.2) vs. 119.7 (100.8) x 10(9)/l; P =
      0.0025] than the 390 patients treated in 2002-2003. Thirty-day mortality was
      reduced in 2005-2006 (20.4% vs. 31.5%; P = 0.0002) and at 90-day (22.4% vs.
      34.6%; P < 0.0001) as compared to 2002-2003. CONCLUSIONS: In patients who
      experience massive bleeding, HCR with platelets and plasma, as guided by
      thrombelastography, is associated with improved survival. While confirmation from
      a randomized controlled trial is urgently needed, HCR may be considered in these
      patients.

PMID- 19152604
TI  - Post-transfusion stability of haemoglobin mass.
AB  - BACKGROUND AND OBJECTIVES: Total haemoglobin mass (tHb) as a direct parameter of
      the blood system and ultimate target of all blood transfusions has not been
      evaluated for its post-transfusion survival and stability. Therefore, the purpose
      of this study was to investigate the latter which may also be relevant from an
      anti-doping perspective as autologous blood transfusions remain impossible to
      detect. MATERIALS AND METHODS: The tHb was determined by the CO rebreathing
      method prior to and after donation of 1 unit of whole blood, as well as prior to
      and after reinfusion (weekly up to 56 days) of the erythrocyte concentrate in 10
      men (28 +/- 7 years, 181 +/- 7 cm, 76 +/- 12 kg). RESULTS: The mean tHb content
      of the derived erythrocyte concentrate was 60 +/- 3 g, while the net tHb
      increases after transfusion of 51 g (95% confidence intervals 33-69 g) permitted
      proof of an elevated tHb for at least 56 days after transfusion. CONCLUSION: The
      results show that an elevated tHb induced by autologous transfusion allowed
      continuous identification although, as expected, a slow decrease of tHb has been
      revealed in the observation period. In reference to anti-doping, CO rebreathing
      permits proof of a supraphysiologically elevated tHb but possibly only if a
      stable baseline value is known.

PMID- 19152605
TI  - An improved method for the determination of Fc function of immunoglobulins.
AB  - BACKGROUND AND OBJECTIVES: The Fc function assay of immunoglobulin G is performed
      to ensure that the biological activity of the molecule is not compromised during
      purification and storage. The current British Pharmacopoeia (BP) method is
      cumbersome, time consuming and requires a continuous source of fresh red blood
      cells. We have modified the technique to improve the convenience, throughput and
      reproducibility of the assay by using frozen red blood cells, a microtitre plate
      format and electronic derivative analysis for processing results. MATERIALS AND
      METHOD: Immunoglobulin G samples were assayed using either the BP Fc function
      procedure or a new procedure incorporating frozen cells, microtitre format and
      electronic derivative analysis. RESULTS: The Fc function results demonstrated
      that there was no significant difference between the BP and the new improved
      procedure. CONCLUSION: In this study, we demonstrated that a new Fc function
      assay incorporating frozen red blood cells, microtitre format and derivative
      analysis of haemolysis curves has been shown to be comparable to the standard BP
      procedure. It offers a more convenient and quicker means of performing analysis
      of Fc function of immunoglobulins.

PMID- 19152606
TI  - A simple filtration system for red blood cell depletion and volume reduction in
      routine processing of human umbilical cord blood.
AB  - BACKGROUND AND OBJECTIVES: Currently, stem cells and other progenitor cells are
      obtained from human umbilical cord blood (HUCB) using a variety of methods that
      are designed primarily for red blood cell depletion and volume reduction prior to
      freezing and storage. Some of these methods are very cumbersome and involve
      several steps that may result in significant cell loss. Therefore, processes that
      minimize the loss of haematopoietic stem and progenitor cells (HSPC) remains very
      critical. In the present study, we describe a simple filtration process for
      achieving both volume reduction and red blood cell depletion in a 'closed sterile
      system' with significant recovery of viable HSPC. MATERIALS AND METHODS: About 80
      100 ml of HUCB were collected into citrate-phosphate-dextrose-adenine 1
      anticoagulant. Each HUCB was divided into 25-70-ml aliquots and then either
      diluted with isotonic saline or filtered without any prior dilution with an
      experimental Red Cell Volume Reduction System (RCVRS). The HSPCs were recovered
      by retrograde rinsing of the filter with an isotonic stem cell recovery solution.
      The viability, colony forming properties, leucocytes and CD34+ cells recoveries
      were determined. RESULTS: The mean volume of the HUCB before processing was
      reduced from 43.9 +/- 7.9 ml to 11.8 +/- 0.7 ml (n = 55) with red blood cell
      depletion of 85.2 +/- 3.7%. Diluting the HUCB with isotonic saline prior to
      processing with RCVRS increased the red blood cell depletion to 91.9 +/- 3.0% (n
      = 7) without any significant loss in viability or cell recovery. The mean
      viability of the RCVRS-processed HUCB was not significantly different from the
      control unprocessed blood (96.60 +/- 1.90 vs. 96.63 +/- 2.12%; P > 0.05). The
      mean recoveries of the CD34+ and the haematopoietic clonogenic progenitor cells
      with the filter were 83.9 +/- 26.8 (n = 40) and 99.9 +/- 27.9% (n = 35),
      respectively. CONCLUSION: The present results show that the RCVRS provides a
      simple and easy-to-use process for obtaining red blood cell depletion and volume
      reduction of HUCB with good cell viability and recoveries.

PMID- 19152607
TI  - International Society of Blood Transfusion Committee on terminology for red blood
      cell surface antigens: Macao report.

PMID- 19152608
TI  - Clinical and laboratory practices in investigation of suspected transfusion
      transmitted bacterial infection: a survey of Canadian hospitals.
AB  - Transfusion of a bacterially contaminated blood product can have serious
      consequences. We undertook an electronic survey of representative Canadian
      hospitals to determine current clinical and laboratory practices for
      investigating such reactions, prior to the development of national guidelines.
      There was considerable variability in symptoms and signs that would trigger
      investigation of possible contamination. The most frequent laboratory
      investigations performed were aerobic blood cultures of recipients and the
      residual component. If there is no residual product in the component bag, 36% of
      respondents would use a segment to perform testing. Guidelines could be helpful
      in improving and standardizing these practices.

PMID- 19152609
TI  - Human immunodeficiency virus 1 subtypes detected in Scottish blood donors.
AB  - The aim of our study was to determine human immunodeficiency virus 1 subtypes in
      Scottish blood donors. We were able to document virus subtypes present in this
      population over a period of 19 years and examine associated risk factors where
      available. Subtype B was found to be the predominant cause of human
      immunodeficiency virus 1 infection in Scottish blood donors with subtype C
      increasing in this population after 2002. Non-B subtypes were found mainly in
      heterosexuals but also in all other risk categories with the exception of men
      having sex with men (MSM). Within Scotland there is an increase in transmission
      via heterosexual contact and the consequential introduction of non-B subtypes.

PMID- 19152610
TI  - Accumulation of soluble inflammatory mediators between blood donation and pre
      storage leucocyte depletion.
AB  - BACKGROUND AND OBJECTIVES: Leucocyte-derived cytokines accumulate in stored whole
      blood. Pre-storage leucocyte depletion has reduced cytokine levels and,
      consequently, febrile non-haemolytic transfusion reactions. As leucocyte
      filtration and component separation can be performed until 24 h after donation,
      we hypothesized that within this time, inflammatory cytokines might accumulate.
      MATERIALS AND METHODS: Serial plasma samples were collected 4, 10 and 20 h after
      donation and cytokine concentrations were measured. RESULTS: Interleukin-8
      increased > 20-fold and soluble CD40 ligand > sixfold during the observation
      time, less pronounced changes for several other mediators were also observed.
      CONCLUSION: Leucocyte depletion within 10 h of blood donation will reduce the
      concentrations of pyrogenic mediators.

PMID- 19152611
TI  - Massive transfusion in patients with severe traumatic injuries.

PMID- 19152612
TI  - On the quality of transfused packed red blood cell concentrates in Trauma
      Registry of the Deutsche Gesellschaft fur Unfallchirurgie-affiliated centres and
      hospitals.

PMID- 19152613
TI  - Tibial plateau leveling osteotomy or tibial tuberosity advancement?
AB  - OBJECTIVE: To review the proposed biomechanical basis of the tibial plateau
      leveling osteotomy (TPLO) and tibial tuberosity advancement (TTA) and
      recommendations for these techniques. STUDY DESIGN: Literature review. METHODS:
      Literature search through Ovid Medline Plus, Pub Med, CAB Abstracts, and
      conference proceedings abstracts (August 1983 to March 2008). RESULTS: TPLO and
      TTA stabilize the cranial cruciate ligament (CrCL) deficient stifle joint
      neutralizing tibiofemoral shear forces by altering the geometry of the proximal
      aspect of the tibia. Stability is attained by placing the joint in a functionally
      greater flexion angle so that the patellar tendon angle (PTA) remains < or =90
      degrees. Both procedures target slightly differing endpoints, the significance of
      which is unknown. Many of the biomechanical variables investigated appear to
      favor the TTA; however, TPLO appears to have more clinical versatility. The
      clinical ramifications of these differences remain to be determined but the
      reported results for both procedures are comparable. Only the early results of
      these techniques have been reported, which is reflected in the relatively high
      number of complications associated with the early learning curve for both
      procedures. CONCLUSIONS: There are many similarities between TPLO and TTA
      although it remains to be fully elucidated if either procedure is superior and
      under what conditions. CLINICAL RELEVANCE: TPLO and TTA are effective at
      returning dogs with a CrCL-deficient stifle joint to good limb function. Surgeon
      discretion and case selection drive selection of TPLO or TTA based mostly on
      anecdotal evidence and personal experience.

PMID- 19152614
TI  - Effect of tibial plateau leveling osteotomy on femorotibial contact mechanics and
      stifle kinematics.
AB  - OBJECTIVE: To evaluate the effects of tibial plateau leveling osteotomy (TPLO) on
      femorotibial contact mechanics and 3-dimensional (3D) kinematics in cranial
      cruciate ligament (CrCL)-deficient stifles of dogs. STUDY DESIGN: In vitro
      biomechanical study. ANIMALS: Unpaired pelvic limbs from 8 dogs, weighing 28-35
      kg. METHODS: Digital pressure sensors placed subjacent to the menisci were used
      to measure femorotibial 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. Three-dimensional static poses of
      the stifle were obtained using a Microscribe digitizing arm. Each specimen was
      tested under normal, CrCL-deficient, and TPLO-treated conditions. Repeated
      measures analysis of variance with a Tukey post hoc test (P<.05) was used for
      statistical comparison. RESULTS: Significant disturbances to all measured contact
      mechanical variables were evident after CrCL transection, which corresponded to
      marked cranial tibial subluxation and increased internal tibial rotation in the
      CrCL-deficient stifle. No significant differences in 3D femorotibial alignment
      were observed between normal and TPLO-treated stifles; however, femorotibial
      contact area remained significantly smaller and peak contact pressures in both
      medial and lateral stifle compartments were positioned more caudally on the
      tibial plateau, when compared with normal. CONCLUSION: Whereas TPLO eliminates
      craniocaudal stifle instability during simulated weight bearing, the procedure
      fails to concurrently restore femorotibial contact mechanics to normal. CLINICAL
      RELEVANCE: Progression of stifle osteoarthritis in dogs treated with TPLO may be
      partly the result of abnormal stifle contact mechanics induced by altering the
      orientation of the proximal tibial articulating surface.

PMID- 19152615
TI  - Effect of tibial tuberosity advancement on femorotibial contact mechanics and
      stifle kinematics.
AB  - Objective- To evaluate the effects of tibial tuberosity advancement (TTA) on
      femorotibial contact mechanics and 3-dimensional kinematics in cranial cruciate
      ligament (CrCL)-deficient stifles of dogs. Study Design- In vitro biomechanical
      study. Animals- Unpaired pelvic limbs from 8 dogs, weighing 28-35 kg. Methods-
      Digital pressure sensors placed subjacent to the menisci were used to measure
      femorotibial 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 . Three-dimensional static poses of the stifle were
      obtained using a Microscribe digitizing arm. Each specimen was tested under
      normal, CrCL-deficient, and TTA-treated conditions. Repeated measures analysis of
      variance with a Tukey post hoc test (P<.05) was used for statistical comparison.
      Results- Significant disturbances to all measured contact mechanic parameters
      were evident after CrCL transection, which corresponded to marked cranial tibial
      subluxation and internal tibial rotation in the CrCL-deficient stifle. No
      significant differences in any contact mechanic and kinematic parameters were
      detected between normal and TTA-treated stifles. Conclusion- TTA eliminates
      craniocaudal stifle instability during simulated weight-bearing and concurrently
      restores femorotibial contact mechanics to normal. Clinical Relevance- TTA may
      mitigate the progression of stifle osteoarthritis in dogs afflicted with CrCL
      insufficiency by eliminating cranial tibial thrust while preserving the normal
      orientation of the proximal tibial articulating surface.

PMID- 19152616
TI  - Biomechanical comparison of two alternative tibial plateau leveling osteotomy
      plates with the original standard in an axially loaded gap model: an in vitro
      study.
AB  - OBJECTIVE: To compare the axial compression stiffness of osteotomized canine
      tibiae stabilized with Slocum, Securos, or Synthes plates after a tibial plateau
      leveling osteotomy (TPLO) procedure. STUDY DESIGN: In vitro, paired comparison of
      cadaveric tibial constructs subjected to mechanical testing under an axial load.
      SAMPLE POPULATION: Canine tibiae (n=16 pairs) from skeletally mature male and
      female dogs of various breeds (18-55 kg). METHODS: Tibial pairs (n=16) were
      randomly assigned to 1 of 2 study cohorts (n=8 pairs/cohort): cohort 1, tibial
      osteotomy stabilization with a Slocum or a Securos plate, or cohort 2, tibial
      osteotomy stabilization with a Slocum or a Synthes plate. One tibia from each
      pair was stabilized with 1 of each plate design assigned to the cohort after
      TPLO. A 3.2 mm osteotomy gap was maintained during plate application in all
      constructs. Load and axial displacement were recorded while constructs were
      loaded to 2000 N in axial compression. Failure loads were not reported because no
      distinct yield point or failure point was evident within the load range for many
      specimens. Failure modes were recorded for each construct, and photographs of
      typical failures were obtained. Stiffness (N/mm) was calculated from load
      displacement curves. Paired comparisons of mean stiffness were performed within
      study groups using a paired t-test. Significance was set at P<.05. RESULTS: The
      mean construct stiffnesses for the Slocum (383+/-183 N/mm) and Securos (258+/
      64.1 N/mm) constructs were not significantly different (P=.164; power=0.566). The
      mean construct stiffness for the Synthes constructs (486+/-91.0 N/mm) was
      significantly greater than that of the Slocum constructs (400+/-117 N/mm);
      P=.0468. Modes of failure for the Slocum (16/16) and Securos (8/8) constructs
      included plastic deformation of the implant with valgus deformity combined with
      fibular luxation (2/16 Slocum; 1/8 Securos) or fibular fracture (2/16 Slocum; 4/8
      Securos). Most Synthes constructs underwent elastic deformation (7/8). One
      Synthes construct fractured in the sagittal plane through the tibial plateau
      depression at the point of load application. CONCLUSIONS: The Slocum and Securos
      plate/tibia construct have similar stiffness, whereas the Synthes/tibia
      constructs are significantly stiffer than the Slocum/tibia constructs. Modes of
      fixation failure observed in this model were consistent with TPLO fixation
      failures observed clinically. CLINICAL RELEVANCE: Construct stiffness in axial
      load varies with implant type. Implants that confer higher stiffness to the
      construct may result in greater fixation stability in tibial metaphyseal
      osteotomies.

PMID- 19152617
TI  - Biomechanical analysis of the three-dimensional motion pattern of the canine
      cervical spine segment C4-C5.
AB  - OBJECTIVE: To study the kinematics of cervical spine segment C(4)-C(5) and its
      association with disc dimensions and the coupled motion (CM) in relation to
      primary motion (PM). STUDY DESIGN: Cadaveric biomechanical study. ANIMALS:
      Cadavers of large breed dogs (>20 kg; n=11). METHODS: Spines were freed from
      muscles. Radiographs were taken orthogonal to the C(4)-C(5) disc space and disc
      thickness, endplate width, and height were measured. Spines were mounted on a
      simulator for 3-dimensional motion analysis. Data were recorded with an
      optoelectronic motion analysis system. Range of motion (ROM) and neutral zone
      (NZ) were determined in the direction of flexion/extension, left/right lateral
      bending, and left/right axial rotation, as well as the ROM of CM. RESULTS: ROM in
      flexion and extension was similar; there was no CM in flexion/extension.
      Left/right axial rotation and left/right lateral bending were coupled to the same
      side. CM was 1.72 and 3.56 times the ROM of the PM in lateral bending and axial
      rotation, respectively. Disc dimensions were positively correlated with body
      weight. Flexion/extension magnitude was significantly reduced for larger
      endplates, but axial rotation was not influenced. Lateral bending had no
      correlation with weight or disc dimensions. CONCLUSION: Left/right lateral
      bending and left/right axial rotation are coupled differently in the C(4)-C(5)
      segment in dogs compared with humans. CLINICAL RELEVANCE: The canine C(4)-C(5)
      spinal segment has unique motion coupling patterns that should be considered for
      dynamic implant designs.

PMID- 19152618
TI  - Descriptive histomorphometric ingrowth analysis of the Zurich cementless canine
      total hip acetabular component.
AB  - OBJECTIVES: To (1) determine bone contact with the outer surface and ingrowth
      into the perforated outer shell of the Kyon acetabular component at 2, 6, and 12
      months after total hip replacement (THR) and (2) determine correlation between
      radiographic lucency surrounding the cup-bone interface and bone contact and
      ingrowth. STUDY DESIGN: Experimental study. ANIMALS: Large breed dogs (n=11) with
      and without hip dysplasia. METHODS: Force platform gait analysis was performed
      preoperatively and 2, 6, and 12 months after THR. Curvilinear length of lucency
      (CLL) was measured on pelvic radiographs. Tissue contact with the outer cup and
      ingrowth into the cup were determined histomorphometrically at 2, 6, and 12
      months. RESULTS: Peak vertical force and vertical impulse of the treated and
      control hind limb were not significantly different at any time. Median bone
      contact with the outer cup surface was 77%, 48%, and 76% at 2, 6, and 12 months,
      respectively. Median bone ingrowth into the cup perforations was 50%, 20%, and
      44% at 2, 6, and 12 months, respectively. Median bone ingrowth to the inner cup
      surface was minimal at any time. CLL did not correlate with bone ingrowth.
      CONCLUSIONS: Bone ingrowth into cup perforations occurred in each dog and was
      already present 2 months after THR, but most of the inner cup space remained
      vacant. CLINICAL RELEVANCE: Radiographic lucency surrounding the cup-bone
      interface does not allow assessment of bone contact with the outer surface or
      bone ingrowth into the Kyon cup in dogs without clinical problems.

PMID- 19152619
TI  - Zurich cementless total hip replacement: retrospective evaluation of 2nd
      generation implants in 60 dogs.
AB  - OBJECTIVE: To evaluate the results of application, and identify complications, of
      the 2nd generation of Zurich Cementless Total Hip Replacement (ZCTHR). STUDY
      DESIGN: Case series. ANIMALS: Client-owned dogs (n=60) that had ZCTHR (n=65).
      METHODS: Dogs with ZCTHR (2001-2003) with a minimum follow-up > or =6 months were
      evaluated. Data included signalment, cup position, longest follow-up,
      complications, management of complications and outcome. RESULTS: Mean follow-up
      was 22.68 months. Eleven cases (17%) had postoperative complications: femoral
      fracture (n=1; 1.5%), prosthesis luxation (7; 11%), cup loosening (2; 3%), and
      implant failure (1; 1.5%); 9 cases were successfully revised. Explantation of
      implants was performed in 1 case because of infection, and 1 dog was euthanatized
      after reluxation. CONCLUSIONS: ZCTHR can restore function in dogs affected by
      disabling diseases of the coxofemoral joint. The press-fit fixation of the cup
      allowed for corrections in cases of incorrect positioning. Cases with aseptic
      loosening were revised successfully by impacting larger cups. Newer stems of this
      generation are shot peening treated to increase their resistance to breakage. In
      our cases, infection is a disastrous event, leading to implant removal. After
      resolution of complications, a successful final outcome was achieved in 97% of
      THR. CLINICAL RELEVANCE: ZCTHR offers a reliable alternative for treating dogs
      with disabling diseases of the hip joints.

PMID- 19152620
TI  - Revision of cemented total hip arthroplasty with cementless components in three
      dogs.
AB  - OBJECTIVE: To report revision of cemented total hip arthroplasty failure with
      cementless components in 3 dogs. STUDY DESIGN: Clinical case reports. ANIMALS:
      Dogs with total hip arthroplasty failure (n=3). METHODS: Cementless total hip
      arthroplasty revision was performed in 3 dogs with previously cemented femoral
      and acetabular components. All dogs required revision of the femoral component
      and 1 dog also required revision of the acetabular component. RESULTS: Revisions
      resulted in a stable functional prosthesis with successful bone integration.
      CONCLUSIONS: Use of cementless components may be a viable option for revision of
      loosened cemented prosthesis after explantation of failed cemented canine total
      hip replacements. CLINICAL RELEVANCE: Failed canine-cemented total hip
      arthroplasties can be successfully revised with cementless components.

PMID- 19152621
TI  - Successful cementless cup reimplantation using cortical bone graft augmentation
      after an acetabular fracture and cup displacement.
AB  - OBJECTIVE: To report repair of a periprosthetic acetabular fracture with
      concurrent component displacement after cementless total hip arthroplasty (THA).
      STUDY DESIGN: Clinical case report. ANIMALS: Dog (n=1) with an acetabular
      fracture after THA. METHODS: Acetabular repair was performed on a highly
      comminuted periprosthetic acetabular fracture after cementless THA. A bulk,
      structural corticocancellous autograft from the ipsilateral ilial wing was used
      for repair and reconstruction of the dorsal acetabular wall before reimplantation
      of a cementless acetabular component. RESULTS: Repair of a periprosthetic
      acetabular fracture with a bulk structural autograft was successful in
      reconstruction of the dorsal acetabular wall and in reestablishing a stable,
      functional cementless THA acetabular prosthesis. CONCLUSIONS: Structural
      corticocancellous autografts from the ilium can be successfully used in repair of
      periprosthetic acetabular fractures after THA. CLINICAL RELEVANCE: Structural
      corticocancellous grafting from the ilium can be considered as a treatment option
      for repair of periprosthetic acetabular fractures after THA.

PMID- 19152622
TI  - Total hip replacement in an alpaca using a cementless implant.
AB  - OBJECTIVE: To report use of a cementless total hip prosthesis in an alpaca. STUDY
      DESIGN: Case report. ANIMALS: Alpaca (n=1) with chronic craniodorsal coxofemoral
      luxation. METHODS: A 2.5-year-old Suri alpaca, 3 months pregnant, was admitted
      for evaluation of acute onset severe left hind limb lameness (grade 4/5) of 6
      weeks duration. After diagnosis of craniodorsal luxation of the left femoral
      head, total hip replacement (THR) using a cementless implant was performed
      because of the poor prognosis for reduction of a chronic luxation. RESULTS: A
      press-fit prosthesis was used and the alpaca delivered a live cria 8 months
      later. Persistent mild mechanical lameness remained after surgery, with moderate
      reduction in mobility of the coxofemoral joint. The prosthesis was stable and
      correctly positioned at 7 weeks and at 9 months. There was mild exostosis
      surrounding the proximal aspect of the femur at 9 months, and Steinmann pins used
      to repair the trochanteric osteotomy were removed because of migration. At 1
      year, the alpaca has a slight gait abnormality, remains with the herd on pasture
      and has been re-bred. CONCLUSION: Chronic coxofemoral luxation in an alpaca can
      be managed by THR. CLINICAL RELEVANCE: THR is a viable treatment option in
      alpacas with severe coxofemoral disease.

PMID- 19152623
TI  - Comparison of alternate and simultaneous tensioning of wires in a single-ring
      fixator construct.
AB  - OBJECTIVE: To measure and compare the strain of wires tensioned with alternate
      (ALT) and simultaneous (SIM) tensioning in a single-ring fixator construct and
      compare the stiffness of these constructs under axial loading. STUDY DESIGN:
      Experimental mechanical study. SAMPLE POPULATION: Twenty-four, 84 mm diameter,
      single-ring constructs. METHODS: Twenty-four, 84 mm diameter, single-ring
      constructs were assembled using 2 1.6 mm wires placed at a 60 degrees angle
      tensioned with either ALT or SIM technique to 90 kg tension. Voltage data from a
      strain gauge were recorded during the wire-tensioning process, cyclic axial
      loading, and load-to-failure testing. Wire strains were calculated for each wire
      and compared within constructs and between ALT and SIM groups. Construct
      stiffness was compared between groups. RESULTS: There was no difference between
      the tensioning methods in final wire strains after initial tensioning for both
      the wire below the ring (W1; P=.698) and the wire above the ring (W2; P=.233).
      There was also no difference in final wire strains within each tensioning method
      group (ALT, P=.289; SIM, P=.583). Loss of wire strain (3.5-5%) occurred after
      cyclic loading for both wires in both groups. There was no difference in
      construct stiffness between the ALT and SIM groups (P=.126). Mode of failure was
      by wire breakage in all constructs and occurred most frequently in W1.
      CONCLUSION: ALT tensioning of wires produced similar wire strains within a single
      ring construct after initial tensioning to SIM tensioned wires. There was no
      difference in construct stiffness under axial loading between AIM and SIM
      tensioned constructs. CLINICAL RELEVANCE: ALT tensioning of wires in a single
      ring fixator construct can be used as an alternative to SIM tensioning, as
      similar initial wire tensions are achieved.

PMID- 19152624
TI  - Hilar liver resection in dogs.
AB  - OBJECTIVE: To describe hepatic vasculobiliary anatomy important to hilar liver
      lobe resection in the dog. STUDY DESIGN: Experimental study. ANIMALS: Canine
      cadavers (n=7). METHODS: The vasculobiliary system of 7 fresh canine livers was
      injected with a polymer. The parenchyma was dissected at the level of the hilus
      to determine the vascular and biliary supply to each liver lobe, and then
      macerated with a corrosion preparation. The information gathered was used to
      describe a surgical approach for hilar liver lobe resection. RESULTS: Each liver
      lobe had a single hepatic artery and biliary duct. The location of these
      structures was consistent, although minor variations existed (dorsal versus
      ventral to the lobar portal vein) in the left lateral lobe and papillary process
      in 2 specimens. Most liver lobes (34/49) were supplied by 1 lobar portal vein and
      drained by 1 lobar hepatic vein (39/49). The location of the portal and hepatic
      veins was consistent among specimens. CONCLUSIONS: The left division is the most
      mobile of the liver lobes and each lobe can be removed separately or en bloc.
      Because of the location of the hepatic veins, the central division is best
      removed as a single unit. The right lateral lobe can be removed individually or
      together with the caudate process. The papillary process is removed by itself.
      CLINICAL RELEVANCE: A hilar liver lobectomy technique can provide an alternative
      approach to conventional procedures for tumors that encroach upon the hilus of
      the liver.

PMID- 19152625
TI  - Lateral thoracic artery axial pattern flap in cats.
AB  - OBJECTIVE: To describe the location of the lateral thoracic artery (LTA),
      determine dimensions of an axial pattern flap based on this artery, and report
      use of this flap in 2 cats. STUDY DESIGN: Ex vivo study and case reports.
      ANIMALS: Cat cadavers (n=8); cats (n=2) with thoracic limb skin defects. METHODS:
      Dissection of the LTA was carried out on 1 side of each cadaver and the
      contralateral side was used for injection studies. In 4 specimens, the LTA was
      cannulated and injected with positive contrast material and the flap was raised
      and radiographed. In 4 specimens, the flap was injected with methylene blue.
      Adequacy of flap injection was subjectively evaluated and leakage of methylene
      blue from the cut edge was noted. RESULTS: The cutaneous location of the LTA
      caudal to the triceps muscle was confirmed. Mean flap size was 8.7 cm x 15.5 cm
      for a mature, average-sized cat. Perfusion of the entire flap was demonstrated
      and viability of the flap was confirmed in 2 clinical cases. CONCLUSION: The LTA
      flap is useful for repair of skin defects of the brachium and antebrachium in
      cats. CLINICAL RELEVANCE: The LTA flap is an alternative technique for repair of
      skin defects involving the thoracic limb of cats.

PMID- 19152626
TI  - Evaluation of a collagenase generated osteoarthritis biomarker in naturally
      occurring canine cruciate disease.
AB  - OBJECTIVE: To determine the clinical value of a novel osteoarthritis (OA)
      biomarker in detecting canine cruciate disease. STUDY DESIGN: Cross sectional
      clinical study. ANIMALS: Dogs (n=22) with cranial cruciate ligament (CCL) rupture
      and 12 control dogs. METHODS: Concentrations of collagenase-generated cleavage
      epitope of type II collagen (Col2-3/4C(long mono), or C2C) in serum, urine, and
      joint fluid were compared between a group of dogs with CCL rupture and a control
      group. Correlation of C2C concentrations to the clinical stage of stifle OA was
      also evaluated. RESULTS: There were no significant differences in C2C
      concentrations in serum, urine, and joint fluid between groups (P>.05).
      Subjective scores of lameness, joint effusion, osteophytosis were significantly
      more severe in the CCL rupture group compared with the control group (P<.05).
      There was no significant correlation of C2C concentrations with clinical stage of
      stifle OA (P>.05). CONCLUSION: This OA biomarker did not detect pathology
      associated with CCL rupture. Our results suggest that collagenase-specific
      degradation of type II collagen in articular cartilage may not be involved in the
      early stage of naturally occurring canine cruciate disease, and that pathology
      associated with naturally occurring CCL rupture is different from that of
      experimental OA model. CLINICAL RELEVANCE: C2C is not clinically useful in
      detecting CCL rupture in dogs.

PMID- 19152627
TI  - Validation of a rapid parathyroid hormone assay and intraoperative measurement of
      parathyroid hormone in dogs with benign naturally occurring primary
      hyperparathyroidism.
AB  - OBJECTIVES: To (1) validate a rapid chemiluminescent parathyroid hormone (PTH)
      assay, (2) determine it's usefulness locating a parathyroid nodule(s), and (3)
      determine if >50% decrease in PTH corresponds with excision of autonomously
      functioning parathyroid tissue. STUDY DESIGN: Prospective cohort study. ANIMALS:
      Dogs (n=12) with naturally occurring primary hyperparathyroidism and 25 healthy
      dogs. METHODS: The assay was validated with linearity, precision, and intermethod
      comparison. Preoperative and postoperative systemic plasma PTH concentrations,
      measured from saphenous venous blood, were compared. Intraoperative local PTH
      concentrations were measured in right and left jugular venous blood before and
      after surgical excision of the grossly abnormal parathyroid gland(s). RESULTS:
      Within run and day-to-day precisions were acceptable (coefficient of variation
      <15%). Dilutional parallelism was used to demonstrate high correlation between
      measured and calculated PTH concentrations (R(2)=0.99). The assay methods had
      good correlation but numerical results of the rapid assay were usually lower than
      the immunoradiometric assay. Seven of 12 dogs had uniglandular disease and five
      had multiglandular disease. Systemic and local PTH concentrations decreased >50%
      in all the dogs after excision of the parathyroid gland(s). Mean preoperative
      systemic plasma PTH concentrations were significantly higher than mean
      postoperative systemic concentrations. Local PTH concentrations could not be used
      reliably to differentiate the side of the autonomously functioning gland(s).
      Hypercalcemia resolved postoperatively in all the dogs. CONCLUSION: This assay
      measures PTH in dogs. Rapid PTH measurement provided documentation of decreased
      PTH concentration after removal of autonomously functioning parathyroid tissue.
      CLINICAL RELEVANCE: Use of this assay allows documentation of a significant
      decrease in PTH concentration after excision of autonomously functioning
      parathyroid tissue.

PMID- 19152628
TI  - The race for chemical and biological space: drug discovery and innovative
      technologies.

PMID- 19152629
TI  - AILERON Therapeutics.

PMID- 19152630
TI  - The thermolysin family (M4) of enzymes: therapeutic and biotechnological
      potential.
AB  - Zinc containing peptidases are widely distributed in nature and have important
      roles in many physiological processes. M4 family comprises numerous zinc
      dependent metallopeptidases that hydrolyze peptide bonds. A large number of these
      enzymes are implicated as virulence factors of the microorganisms that produce
      them and are therefore potential drug targets. Some enzymes of the family are
      able to function at the extremes of temperatures, and some function in organic
      solvents. Thereby enzymes of the thermolysin family have an innovative potential
      for biotechnological applications.

PMID- 19152631
TI  - Combining cluster analysis, feature selection and multiple support vector machine
      models for the identification of human ether-a-go-go related gene channel
      blocking compounds.
AB  - Blockade of the human ether-a-go-go related gene potassium channel is regarded as
      a major cause of drug toxicity and associated with severe cardiac side-effects. A
      variety of in silico models have been reported to aid in the identification of
      compounds blocking the human ether-a-go-go related gene channel. Herein, we
      present a classification approach for the detection of diverse human ether-a-go
      go related gene blockers that combines cluster analysis of training data, feature
      selection and support vector machine learning. Compound learning sets are first
      divided into clusters of similar molecules. For each cluster, independent support
      vector machine models are generated utilizing preselected MACCS structural keys
      as descriptors. These models are combined to predict human ether-a-go-go related
      gene inhibition of our large compound data set with consistent experimental
      measurements (i.e. only patch clamp measurements on mammalian cell lines). Our
      combined support vector machine model achieves a prediction accuracy of 85% on
      this data set and performs better than alternative methods used for comparison.
      We also find that structural keys selected on the basis of statistical criteria
      are associated with molecular substructures implicated in human ether-a-go-go
      related gene channel binding.

PMID- 19152633
TI  - Cationic amphiphilic polyproline helices: side-chain variations and cell-specific
      internalization.
AB  - Cell-penetrating peptides present an attractive and efficient tool for the
      delivery of a variety of cell impermeable cargoes across the cellular membrane.
      Cell-penetrating peptides usually consist of short basic peptide sequences that
      are internalized by a variety of cell lines. Most cell-penetrating peptides lack
      cell specificity, however, which greatly limits their use as efficient
      therapeutic agents. Herein, we present two cell-penetrating peptides displaying a
      type II polyproline helical backbone that are functionalized to contain six
      cationic moieties and two distinctive hydrophobic functionalities, namely
      isobutyl or benzyl groups. The uptake efficiency of these cationic amphiphilic
      polyproline helices was studied in seven different cell lines, six cancerous (MCF
      7, HOS, HT1080, HeLa, KB-FD, KB3-1) and one non-cancerous (WI 38). The cationic
      amphiphilic polyproline helix P11LRR at 50 microM showed high specificity toward
      MCF-7 breast cancer cells. Co-culture experiments with P11LRR demonstrated almost
      exclusive internalization by MCF-7 cells and not WI38. The replacement of the
      isobutyl hydrophobic group with a benzyl moiety resulted in a shift in uptake
      efficiency and specificity across some cell lines. These results demonstrate that
      the type of hydrophobic residues utilized in the creation of cell-penetrating
      peptides can strongly influence the extent and specificity of cellular
      internalization.

PMID- 19152632
TI  - Conformational dynamics of the flexible catalytic loop in Mycobacterium
      tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase.
AB  - In mycobacteria, the biosynthesis of the precursors to the essential isoprenoids,
      isopentenyl diphosphate and dimethylallyl pyrophosphate is carried out by the
      methylerythritol phosphate pathway. This route of synthesis is absent in humans,
      who utilize the alternative mevalonate acid route, thus making the enzymes of the
      methylerythritol phosphate pathway of chemotherapeutic interest. One such
      identified target is the second enzyme of the pathway, 1-deoxy-D-xylulose 5
      phosphate reductoisomerase. Only limited information is currently available
      concerning the catalytic mechanism and structural dynamics of this enzyme, and
      only recently has a crystal structure of Mycobacterium tuberculosis species of
      this enzyme been resolved including all factors required for binding. Here, the
      dynamics of the enzyme is studied in complex with NADPH, Mn2+, in the presence
      and absence of the fosmidomycin inhibitor using conventional molecular dynamics
      and an enhanced sampling technique, reversible digitally filtered molecular
      dynamics. The simulations reveal significant differences in the conformational
      dynamics of the vital catalytic loop between the inhibitor-free and inhibitor
      bound enzyme complexes and highlight the contributions of conserved residues in
      this region. The substantial fluctuations observed suggest that 1-deoxy-D
      xylulose 5-phosphate reductoisomerase may be a promising target for computer
      aided drug discovery through the relaxed complex method.

PMID- 19152634
TI  - The structural and functional role of the B-chain C-terminal arginine in the
      relaxin-3 peptide antagonist, R3(BDelta23-27)R/I5.
AB  - Relaxin-3, a member of the insulin superfamily, is involved in regulating stress
      and feeding behavior. It is highly expressed in the brain and is the endogenous
      ligand for the receptor RXFP3. As relaxin-3 also interacts with the relaxin
      receptor RXFP1, selective agonists and antagonists are crucial for studying the
      physiological function(s) of the relaxin-3/RXFP3 pair. The analog R3(BDelta23
      27)R/I5, in which a C-terminally truncated human relaxin-3 (H3) B-chain is
      combined with the INSL5 A-chain, is a potent selective RXFP3 antagonist and has
      an Arg residue remaining on the B-chain C-terminus as a consequence of the
      recombinant protein production process. To investigate the role of this residue
      in the RXFP3 receptor binding and activation, the analogs R3(BDelta23-27)R/I5 and
      R3(BDelta23-27)R containing the B-chain C-terminal Arg as well as R3(BDelta23
      27)/I5 and R3(BDelta23-27), both lacking the Arg, were chemically assembled and
      their secondary structure and receptor activity assessed. The peptides generally
      had a similar conformation but those with the extra Arg residue displayed a
      significantly increased affinity for the RXFP3. Interestingly, in contrast to
      R3(BDelta23-27)R and R3(BDelta23-27)R/I5, the peptide R3(BDelta23-27) is a weak
      agonist. This suggests that the C-terminal Arg, although increasing the affinity,
      alters the manner in which the peptide binds to the receptor and thereby prevents
      activation, giving R3(BDelta23-27)R/I5 its potent antagonistic activity.

PMID- 19152635
TI  - Peptide nanoparticles as novel immunogens: design and analysis of a prototypic
      severe acute respiratory syndrome vaccine.
AB  - Severe acute respiratory syndrome (SARS) is an infectious disease caused by a
      novel coronavirus that cost nearly 800 lives. While there have been no recent
      outbreaks of the disease, the threat remains as SARS coronavirus (SARS-CoV) like
      strains still exist in animal reservoirs. Therefore, the development of a vaccine
      against SARS is in grave need. Here, we have designed and produced a prototypic
      SARS vaccine: a self-assembling polypeptide nanoparticle that repetitively
      displays a SARS B-cell epitope from the C-terminal heptad repeat of the virus'
      spike protein. Biophysical analyses with circular dichroism, transmission
      electron microscopy and dynamic light scattering confirmed the computational
      design showing alpha-helcial nanoparticles with sizes of about 25 nm.
      Immunization experiments with no adjuvants were performed with BALB/c mice. An
      investigation of the binding properties of the elicited antibodies showed that
      they were highly conformation specific for the coiled-coil epitope because they
      specifically recognized the native trimeric conformation of C-terminal heptad
      repeat region. Consequently, the antisera exhibited neutralization activity in an
      in vitro infection inhibition assay. We conclude that these peptide nanoparticles
      represent a promising platform for vaccine design, in particular for diseases
      that are characterized by neutralizing epitopes with coiled-coil conformation
      such as SARS-CoV or other enveloped viruses.

PMID- 19152636
TI  - Probing the active site of Candida glabrata dihydrofolate reductase with high
      resolution crystal structures and the synthesis of new inhibitors.
AB  - Candida glabrata, a fungal strain resistant to many commonly administered
      antifungal agents, has become an emerging threat to human health. In previous
      work, we validated that the essential enzyme, dihydrofolate reductase, is a drug
      target in C. glabrata. Using a crystal structure of dihydrofolate reductase from
      C. glabrata bound to an initial lead compound, we designed a class of biphenyl
      antifolates that potently and selectively inhibit both the enzyme and the growth
      of the fungal culture. In this work, we explore the structure-activity
      relationships of this class of antifolates with four new high resolution crystal
      structures of enzyme:inhibitor complexes and the synthesis of four new
      inhibitors. The designed inhibitors are intended to probe key hydrophobic pockets
      visible in the crystal structure. The crystal structures and an evaluation of the
      new compounds reveal that methyl groups at the meta and para positions of the
      distal phenyl ring achieve the greatest number of interactions with the
      pathogenic enzyme and the greatest degree of selectivity over the human enzyme.
      Additionally, antifungal activity can be tuned with substitution patterns at the
      propargyl and para-phenyl positions.

PMID- 19152637
TI  - Aromatic organic compounds as scaffolds for metallocarboxypeptidase inhibitor
      design.
AB  - We have identified and characterized a set of quinoline, naphthalene and
      quinazoline derivatives as inhibitors of metallocarboxypeptidases, a class of
      metal-dependent proteolytic enzymes. The aromatic organic compounds were selected
      from a high-throughput screening survey and, with some exceptions, showed a good
      correlation between inhibitory potency and docking energy value. The in vitro
      inhibition tests gave K(i) values in the lower micromolar range for
      metallocarboxypeptidases with different specificities, and a tendency to behave
      as more powerful inhibitors of CPB was observed for most of the compounds tested.
      The kinetic results were further analyzed by structural analysis via molecular
      docking. The most potent aromatic organic inhibitor docks to human CPB mostly
      through burial of its hydrophobic moiety deep into the enzyme's active site cleft
      and by interacting with the catalytic zinc ion. The significance of our results
      in designing inhibitors against disease-related CPs from the identified ligands
      is examined herein.

PMID- 19152638
TI  - Development of predictive 3D-QSAR CoMFA and CoMSIA models for beta
      aminohydroxamic acid-derived tumor necrosis factor-alpha converting enzyme
      inhibitors.
AB  - A three-dimensional quantitative structure-activity relationship study was
      performed on a series of beta-aminohydroxamic acid-derived tumor necrosis factor
      alpha converting enzyme inhibitors employing comparative molecular field analysis
      and comparative molecular similarity indices analysis techniques to investigate
      the structural requirements for the inhibitors, and derive a predictive model
      that could be used for the design of novel tumor necrosis factor-alpha converting
      enzyme inhibitors. log P was used as an additional descriptor in the comparative
      molecular field analysis analysis to study the effects of lipophilic parameters
      on activity. Inclusion of log P did not improve the models significantly. The
      statistically significant model was established with 45 molecules, which were
      validated by a test set of 11 compounds. Ligand molecular superimposition on the
      template structure was performed by the atom-/shape-based root mean square fit
      and database alignment methods. Docked conformer based alignment (V) yielded the
      best predictive comparative molecular field analysis model = 0.673, = 0.860, F
      value = 86.073, predictive r (2) = 0.642, with two components, standard error of
      prediction = 0.394 and standard error of estimates = 0.243 while the comparative
      molecular similarity indices analysis model yielded = 0.635, = 0.858, F-value =
      84.451, predictive r (2) = 0.441 with three components, standard error of
      prediction = 0.393 and standard error of estimates = 0.245. The contour maps
      obtained from three-dimensional quantitative structure-activity relationship
      studies were appraised for activity trends for the molecules analyzed. The
      comparative molecular field analysis models exhibited good external predictivity
      as compared with that of comparative molecular similarity indices analysis
      models. The model generated through comparative molecular field analysis was
      validated with the IK-682. The data generated from this study may guide our
      efforts in designing and predicting the tumor necrosis factor-alpha converting
      enzyme inhibitory activity of novel molecules.

PMID- 19152639
TI  - Characterization of peptide 20-30 of follicle stimulating hormone receptor as an
      antagonist of receptor activity: significance of charged residues.
AB  - We had previously reported the region (20-30) from follicle stimulating hormone
      receptor as being an immunodominant epitope and the smallest reported peptide
      capable of inhibiting hormone binding. We now report it to be an effective
      antagonist of ligand-induced cAMP signalling as well. The region (20-30) of
      follicle stimulating hormone receptor has three charged residues, namely, E(22),
      D(26) and R(29) that are specific to follicle stimulating hormone receptor and
      are conserved in mammals. This study aimed to verify whether the charged residues
      contribute to the activity of the follicle stimulating hormone receptor peptide
      (20-30). This was done using analogs of follicle stimulating hormone receptor
      peptide (20-30), each having an alanine substitution for a corresponding charged
      residue. The analog peptides displayed a loss of activity and could not inhibit
      hormone binding or the subsequent signal transduction. The ability of follicle
      stimulating hormone receptor peptide (20-30) to bind antipeptide antibodies
      against follicle stimulating hormone receptor peptide (9-30) was either decreased
      or abolished with the alanine substituted analog peptides of follicle stimulating
      hormone receptor peptide (20-30). The loss of function led us to verify whether
      there was a conformational change as well. CD spectral analysis did not reveal a
      significant change. These observations indicate that the charged aminoacids
      present in follicle stimulating hormone receptor peptide (20-30) are crucial for
      the observed follicle stimulating hormone antagonistic activity. This information
      could form the basis for the design of novel compounds capable of functioning as
      follicle stimulating hormone antagonists.

PMID- 19152640
TI  - A specific pharmacophore model of Aurora B kinase inhibitors and virtual
      screening studies based on it.
AB  - In this study, 3D-pharmacophore models of Aurora B kinase inhibitors have been
      developed by using HipHop and HypoGen modules in Catalyst software package. The
      best pharmacophore model, Hypo1, which has the highest correlation coefficient
      (0.9911), consists of one hydrogen-bond acceptor, one hydrogen-bond donor, one
      hydrophobic aliphatic moiety and one ring aromatic feature. Hypo1 was validated
      by test set and cross-validation methods. And the specificity of Hypo1 to Aurora
      B inhibitors was examined with the use of selective inhibitors against Aurora B
      and its paralogue Aurora A. The results clearly indicate that Hypo1 can
      differentiate selective inhibitors of Aurora B from those of Aurora A, and the
      ring aromatic feature likely plays some important roles for the specificity of
      Hypo1. Then Hypo1 was used as a 3D query to screen several databases including
      Specs, NCI, Maybridge and Chinese Nature Product Database (CNPD) for identifying
      new inhibitors of Aurora B. The hit compounds were subsequently subjected to
      filtering by Lipinski's rule of five and docking studies to refine the retrieved
      hits, and some compounds selected from the top ranked hits have been suggested
      for further experimental assay studies.

PMID- 19152641
TI  - The fluorinated and chlorinated nuclear localization sequence of the SV 40 T
      antigen.
AB  - Nuclear uptake of the simian virus (SV) 40 T antigen is triggered by a specific
      nuclear localization sequence. However, such a nuclear localization sequence is
      only poorly taken up by the cytoplasm of cells when administered to the culture
      medium. Our aim was to improve the cytoplasmic uptake of the SV 40 T antigen
      nuclear localization sequence. Consequently, we synthesized novel fluorescein
      isothiocyanate-labelled conjugates containing the nuclear localization sequences
      of the SV 40 T antigen and either trichlorobenzoic or trifluorobenzoic acid.
      Applied at 260 microM such halogenated NLS conjugates were nuclearly taken up by
      75-85% of U373 and LN18 glioma cells and resulted in cell death. Nuclear staining
      and cell death were also found at lower concentrations (130 and 65 microM) of
      halogenated nuclear localization sequence conjugates. By contrast only a low
      cellular staining rate and no cell death could be observed after co-incubation
      with a trichlorobenzoic acid or trifluorobenzoic acid-lacking nuclear
      localization sequence conjugate and free, unbound trichlorobenzoic acid or
      trifluorobenzoic acid at the high concentration (260 microM). Such small non
      radioactive fluorinated and chlorinated nuclear localization sequences may be
      used as important components for future antiglioma drug development.

PMID- 19152642
TI  - Cholera toxin inhibitors studied with high-performance liquid affinity
      chromatography: a robust method to evaluate receptor-ligand interactions.
AB  - Anti-adhesion drugs may be an alternative to antibiotics to control infection of
      micro-organisms. The well-characterized interaction between cholera toxin and the
      cellular glycolipid GM1 makes it an attractive model for inhibition studies in
      general. In this report, we demonstrate a high-performance liquid affinity
      chromatography approach called weak affinity chromatography to evaluate cholera
      toxin inhibitors. The cholera toxin B-subunit was covalently coupled to porous
      silica and a (weak) affinity column was produced. The K(D) values of galactose
      and meta-nitrophenyl alpha-D-galactoside were determined with weak affinity
      chromatography to be 52 and 1 mM, respectively, which agree well with IC(50)
      values previously reported. To increase inhibition potency multivalent inhibitors
      have been developed and the interaction with multivalent glycopolypeptides was
      also evaluated. The affinity of these compounds was found to correlate with the
      galactoside content but K(D) values were not obtained because of the
      inhomogeneous response and slow off-rate from multivalent interactions. Despite
      the limitations in obtaining direct K(D) values of the multivalent
      galactopolypeptides, weak affinity chromatography represents an additional and
      valuable tool in the evaluation of monovalent as well as multivalent cholera
      toxin inhibitors. It offers multiple advantages, such as a low sample
      consumption, high reproducibility and short analysis time, which are often not
      observed in other methods of analysis.

PMID- 19152643
TI  - Synthesis and in vitro antibacterial activity of (2S)-N-(substitutedphenyl)-1
      [(2R)-2-[(formylhydroxyamino)methyl]-1-oxohexyl]-2-pyrrolidinecarboxamides as
      potential peptide deformylase inhibitors.
AB  - Gram-positive organisms have re-emerged as the major hospital pathogens, which
      make the unmet medical needs for antibacterial therapy even worse. In searching
      for potent agents against Gram-positive pathogens, novel (2S)-N
      (substitutedphenyl)-1-[(2R)-2-[(formylhydroxyamino)methyl]-1-oxohexyl]-2
      pyrrolidinecarboxamides, analogues of peptide deformylase inhibitor LBM-415 were
      designed, synthesized and evaluated for their antibacterial activities in vitro.
      Many of these compounds exhibited high potency against Gram-positive organisms
      compared with reference agent: LBM-415.

PMID- 19152647
TI  - Microcirculation in mixed arterial/venous ulcers and the surrounding skin:
      clinical study using a laser Doppler perfusion imager and capillary microscopy.
AB  - To treat mixed skin ulcers effectively, it is important to investigate skin
      microcirculation in greater detail. Therefore, we used laser Doppler perfusion
      imaging and capillary microscopy for assessing both subpapillary and nutritive
      microcirculation in four defined regions of the skin in 17 patients with mixed
      ulcers caused by a combination of peripheral arterial occlusive disease and
      chronic venous insufficiency. Laser Doppler area flux was significantly higher in
      the ulcer areas than in the areas without granulation tissue and those in intact
      skin. The flux in the scars was higher than that in the intact skin or in the
      ulcer areas without granulation tissue. Capillary density in the intact skin was
      higher than the densities in nongranulation tissue areas, granulation areas, and
      scar areas (p<0.001 for all comparisons). To conclude, the ulcer areas without
      granulation tissue did not show a healing tendency due to poor subpapillary and
      nutritive perfusion; the granulation tissue exhibited high subpapillary perfusion
      as a sign of healing. In the scars, sufficient blood supply could be detected in
      both layers as a sign of an almost complete healing process. Blood supply in the
      intact skin is, however, already affected by distorted microcirculation in the
      ulcers.

PMID- 19152648
TI  - Aging influences wound healing in patients with chronic lower extremity wounds
      treated in a specialized Wound Care Center.
AB  - With the dramatic increase in the aging population, the study and care of wounds
      in the elderly have become priority topics for both researchers and clinicians.
      The effects of aging on wound healing in humans have remained controversial. The
      study was a 5-year epidemiological evaluation of standardized data collected
      regularly during patients' visits at a specialized Wound Care Center with the aim
      to determine the key factors influencing the healing of chronic lower extremity
      wounds. In this analysis of 1,158 chronic wounds, the frequency of wound closure
      was statistically significantly lower in older patients compared with younger
      patients. The share of closed wounds decreased by nearly 25% in the elderly
      patients (>or=70 years). The relationship between the patient's age and the
      proportion of wound closure was nonlinear. The effect of aging on the frequency
      of wound closure of chronic wounds became clinically apparent after age 60. The
      chronicity of the wounds was illustrated by their recurrent nature, their long
      duration, the presence of multiple wounds, and the frequency of concurrent
      infection. Comorbidity was documented by the coprevalence of up to three
      underlying diseases related to impaired wound healing. The present study clearly
      showed that aging affects chronic wound healing negatively.

PMID- 19152646
TI  - Wound healing essentials: let there be oxygen.
AB  - The state of wound oxygenation is a key determinant of healing outcomes. From a
      diagnostic standpoint, measurements of wound oxygenation are commonly used to
      guide treatment planning such as amputation decision. In preventive applications,
      optimizing wound perfusion and providing supplemental O(2) in the perioperative
      period reduces the incidence of postoperative infections. Correction of wound
      pO(2) may, by itself, trigger some healing responses. Importantly, approaches to
      correct wound pO(2) favorably influence outcomes of other therapies such as
      responsiveness to growth factors and acceptance of grafts. Chronic ischemic
      wounds are essentially hypoxic. Primarily based on the tumor literature, hypoxia
      is generally viewed as being angiogenic. This is true with the condition that
      hypoxia be acute and mild to modest in magnitude. Extreme near-anoxic hypoxia, as
      commonly noted in problem wounds, is not compatible with tissue repair. Adequate
      wound tissue oxygenation is required but may not be sufficient to favorably
      influence healing outcomes. Success in wound care may be improved by a
      personalized health care approach. The key lies in our ability to specifically
      identify the key limitations of a given wound and in developing a multifaceted
      strategy to specifically address those limitations. In considering approaches to
      oxygenate the wound tissue it is important to recognize that both too little as
      well as too much may impede the healing process. Oxygen dosing based on the
      specific need of a wound therefore seems prudent. Therapeutic approaches
      targeting the oxygen sensing and redox signaling pathways are promising.

PMID- 19152649
TI  - Delayed reepithelialization and basement membrane regeneration after wounding in
      mice lacking CXCR3.
AB  - Wound healing is a complex, orchestrated series of biological events that is
      controlled by extracellular components that communicate between cell types to re
      establish lost tissue. We have found that signaling by ELR-negative CXC
      chemokines through their common CXCR3 receptor is critical for dermal maturation
      during the resolving phase. In addition there needs to be complete maturation of
      the epidermis and regeneration of a delineating basement membrane for proper
      functioning. The role of this ligand-receptor system appears confounding as one
      ligand, CXCL4/(PF4), is present during the initial dissolution and two others,
      CXCL10/(IP-10) and CXCL11/(IP-9/I-TAC), are expressed by keratinocytes in the
      later regenerative and resolving phases during which the basement membrane is re
      established. We examined CXCR3 signaling role in healing using a mouse lacking
      this receptor, as all three ligands act solely via the common receptor.
      Reepithelialization was delayed in CXCR3-deficient mice in both full and partial
      thickness excisional wounds. Even at 90 days postwounding, the epidermis of these
      mice appeared less mature with lower levels of E-cadherin and cytokeratin 18. The
      underlying basement membrane, a product of both dermal fibroblasts and epidermal
      keratinocytes, was not fully established with persistent diffuse expression of
      the matrix components laminin 5, collagen IV, and collagen VII throughout the
      wound bed. These results suggest that CXCR3 and its ligands play an important
      role in the re-establishment of the basement membrane and epidermis. These
      studies further establish the emerging signaling network that involves the CXCR3
      chemokine receptor and its ligands as a key regulator of wound repair.

PMID- 19152650
TI  - Effect of estrogen and progesterone on macrophage activation during wound
      healing.
AB  - Age-related impaired wound healing leads to substantial morbidity and mortality
      along with a large financial burden to health services. There is accumulating
      evidence that the tissue damage associated with chronic wounds is initiated and
      propagated by an inappropriately excessive inflammatory response. Research on age
      related impaired wound healing suggests that the decline in sex steroid hormones
      with age may have a substantial influence on the inflammatory response in vivo.
      Topical and systemic estrogen treatments have shown an increased rate of healing
      by reducing inflammation, however the underlying mechanisms are little
      understood. In vitro studies also suggest progesterone may play a role in
      modulating inflammation. Macrophages are essential mediators of inflammation and
      wound healing. Macrophages can be activated in a classical or alternative manner
      in parallel with the T(H)1/T(H)2 dichotomy, respectively. Using a murine
      incisional wound healing model this study was carried out to investigate the
      roles of estrogen and progesterone on macrophage activation during the wound
      healing response. Our findings suggest with a reduction of steroid hormones
      following ovariectomy, alternatively activated macrophage markers (Fizz1 and Ym1)
      were reduced, with this effect being reversed with the administration of estrogen
      or progesterone; suggesting that with the reduction of steroid hormones
      macrophages are activated in a classical manner, promoting inflammation, whereas
      estrogen or progesterone are contributing toward macrophage activation in an
      alternative manner, driving wound repair, angiogenesis, and remodeling.

PMID- 19152651
TI  - Characterizing omental adhesions by culturing cells isolated from a novel in vivo
      adhesion model.
AB  - Although it has been established that postoperative adhesions in the peritoneal
      cavity are the consequence of injury to the peritoneum, there is much controversy
      over the nature of the cells giving rise to this neotissue. Here, we establish a
      novel adhesiogenic model in the rabbit to analyze the phenotype and proliferation
      in vitro of cells comprising adhesion tissue seven days postsurgery. Adhesion
      free omentum tissue was used as control. Cells derived from adhesions and from
      the control omentum were subcultured and characterized through immunofluorescence
      and Western blotting procedures to determine markers of cell differentiation and
      pluripotential, and viability and proliferation assays. Our findings indicate the
      existence of a mesenchymal population in the omentum revealed by markers of
      pluripotent cells with high angiogenic capacity. This population seems to be
      responsible for the adhesions formed in response to mesothelial damage. Depending
      on the local environment, mesenchymal cells are capable of in vivo
      differentiation towards at least two different cell phenotypes rendering two
      types of adhesions with clearly differentiated characteristics. One type of
      adhesion shows a highly vascularized adipose morphology containing cells
      differentiating into a vascular lineage. The other adhesions are fibrous with
      large amounts of collagen and comprised mainly of myofibroblasts conferring less
      compliance to this tissue.

PMID- 19152652
TI  - Prostaglandin E1 prevents liver failure after excessive hepatectomy in the rat by
      up-regulating Cyclin C, Cyclin D1, and Bclxl.
AB  - Prostaglandin E1 (PGE1) has wide-ranging effects on cytoprotection and may play a
      role in preventing liver failure following excessive hepatectomy. We examined the
      effect of PGE1 on hepatocyte apoptosis and liver regeneration after 95%
      hepatectomy in a rat model. PGE1 or vehicle was intravenously administered 30
      minutes before and during hepatectomy. The extent of hepatocyte injury was
      evaluated by serum alanine aminotransferase and aspartate aminotransferase
      levels. To evaluate hepatocyte apoptosis and liver regeneration, terminal
      deoxynucleotidyl transferase dUTP nick end labeling staining and Ki67 labeling
      were performed. The expression levels of Bcl-xL, Bcl-2, Bax, Cyclin C, Cyclin D1,
      Cyclin E, p21, transforming growth factor-beta, plasminogen activator inhibitor
      1, and glyceraldehyde-2-phosphate dehydrogenase mRNA were also examined by
      reverse transcription-polymerase chain reaction. Survival was improved in the
      PGE1 group (26.6%), whereas all rats in the vehicle group died within 60 hours.
      PGE1 significantly suppressed the release of alanine aminotransferase and
      aspartate aminotransferase at 12 hours postoperatively. Pretreatment with PGE1
      significantly increased the Ki67-positive cell count and decreased the terminal
      deoxynucleotidyl transferase dUTP nick end labeling positive cell count after
      hepatectomy, and also significantly increased the expression levels of Bcl-xL,
      Cyclin C, and Cyclin D1. Our results suggest that pretreatment with PGE1 may
      increase survival following hepatectomy by salvaging the remaining liver tissue,
      which it does by inhibiting apoptosis and stimulating hepatocyte proliferation.

PMID- 19152653
TI  - Tyrosine phosphorylation of EGF-R and PDGF-R proteins during acute cutaneous
      wound healing process in mice.
AB  - The effect of topical application of epidermal growth factor (EGF) and platelet
      derived growth factors (PDGFs) on the levels of EGF-R and PDGF-R proteins and
      their tyrosine phosphorylation were analyzed during an acute cutaneous wound
      healing process in mice. The growth factor-treated wounds had optimum levels of
      receptor proteins as early as day 1 compared with the control, which had only a
      basal level. Analysis of the tyrosine phosphorylation of the receptor proteins in
      control and growth factor-treated wounds indicated that they were phosphorylated
      until day 5 after wounding. Only the mature forms of alpha-PDGF-R and beta-PDGF-R
      proteins were phosphorylated and not their precursors. Our results show that
      rapid attainment of maximum levels of growth factor receptor proteins and their
      tyrosine phosphorylation as early as day 1 and the maintenance of the same until
      day 3 appear to aid faster and better wound healing. Topical application of PDGF
      AA alone did not facilitate the wound healing process and it also antagonized the
      EGF-medicated wound healing when applied premixed with EGF or within 30 minutes
      after EGF application. Under these conditions, the receptor proteins were not
      phosphorylated. Thus, an increased and sustained level of EGF-R and PDGF-R
      proteins and their tyrosine phosphorylation appear to accelerate the wound
      healing process.

PMID- 19152654
TI  - Extracorporeal shock wave treatment modulates skin fibroblast recruitment and
      leukocyte infiltration for enhancing extended skin-flap survival.
AB  - Extracorporeal shock wave (ESW) treatment has a positive effect of rescuing
      ischemic skin flaps. This study assessed whether ESW treatment rescues the
      compromised flap tissue by suppressing the apoptosis of ischemic tissue and
      recruiting tissue remodeling. We used a random-pattern extended dorsal-skin-flap
      (10 x 3 cm) rodent model. Thirty-six male Sprague-Dawley rats were divided into
      three groups. Group I, the control group, received no treatment. Group II
      received one session of ESW treatment (500 impulses at 0.15 mJ/mm(2)) immediately
      after surgery. Group III received two sessions of ESW treatment, immediately and
      the day after the surgery. Results indicated that the necrotic area in the flaps
      in group II was significantly smaller than that of the flaps in group I (p<0.01).
      Transferase dUTP-nick end labeling (TUNEL) analysis revealed a significant
      decrease in the number of apoptotic cells in group II. Hydrogen peroxide
      (H(2)O(2)) expression in circulation blood was significantly decreased in group
      II on the day after ESW treatment. Immunohistochemical staining indicated that
      compared with no treatment, ESW treatment could substantially increase
      proliferating cell nuclear antigen (PCNA), endothelial nitric oxide synthase, and
      prolyl 4-hydroxylase (rPH) expression, reduce CD45 expression, and suppress 8
      hydroxyguanosine (8-OG) expression in the ischemic zone of the flap tissue. In
      conclusion, ESW treatment administered at an optimal dosage exerts a positive
      effect of rescuing ischemic extended skin flaps. The mechanisms of action of ESWs
      involve modulation of oxygen radicals, attenuation of leukocyte infiltration,
      decrease in tissue apoptosis, and recruitment of skin fibroblasts, which results
      in increased flap tissue survival.

PMID- 19152655
TI  - Prostaglandin E2 differentially regulates contraction and structural
      reorganization of anchored collagen gels by human adult and fetal dermal
      fibroblasts.
AB  - Contraction and remodeling of granulation tissue by fibroblasts is a crucial
      component of dermal wound healing. Postnatal wounds heal with imperfect repair
      and scar formation, whereas tissue repair in fetal wounds is regenerative.
      Prostaglandin E2 (PGE2) modulates the behavior of fibroblasts in the wound bed.
      This study was designed to investigate the mechanism by which PGE2 regulates an
      in vitro model of granulation tissue, anchored collagen gels, by human adult and
      fetal dermal fibroblasts. We hypothesized that PGE2 differentially regulates
      contraction and remodeling of anchored collagen gels by these fibroblast
      phenotypes. These results indicate that once tension was generated, fetal
      fibroblasts exerted lower contractile forces resulting in less collagen
      contraction. This coincided with less prominent stress fibers, yet fetal
      fibroblasts were able to substantially remodel the collagen architecture. This
      mechanism was differentially modulated by PGE2 and was mimicked with a PGE2
      receptor agonist, indicating a cyclic adenosine monophosphate (cAMP)-dependent
      mechanism through the EP2 receptor. However, direct up-regulation of cAMP led to
      decreases in contraction and remodeling by both fibroblast phenotypes indicating
      an altered signaling pathway. Therefore, targeting cAMP via the EP2 receptor
      could potentially decrease adult fibroblast contractile forces to the levels of
      the fetal fibroblast phenotype in order to decrease dermal scarring.

PMID- 19152656
TI  - Emblica officinalis exerts wound healing action through up-regulation of collagen
      and extracellular signal-regulated kinases (ERK1/2).
AB  - During wound healing, the wound site is rich in oxidants, such as hydrogen
      peroxide, mostly contributed by neutrophils and macrophages. Ascorbic acid and
      tannins of low molecular weight, namely emblicanin A (2,3-di-O-galloyl-4,6-(S)
      hexahydroxydiphenoyl-2-keto-glucono-delta-lactone) and emblicanin B (2,3,4,6-bis
      (S)-hexahydroxydiphenoyl-2-keto-glucono-delta-lactone) present in Emblica
      officinalis (emblica), have been shown to exhibit a very strong antioxidant
      action. We proposed that addition of these antioxidants to the wound
      microenvironment would support the repair process. The present investigation was
      undertaken to determine the efficacy of emblica on dermal wound healing in vivo.
      Full-thickness excision wounds were made on the back of the rat and topical
      application of emblica accelerated wound contraction and closure. Emblica
      increased cellular proliferation and cross-linking of collagen at the wound site,
      as evidenced by an increase in the activity of extracellular signal-regulated
      kinase 1/2, along with an increase in DNA, type III collagen, acid-soluble
      collagen, aldehyde content, shrinkage temperature and tensile strength. Higher
      levels of tissue ascorbic acid, alpha-tocopherol, reduced glutathione, superoxide
      dismutase, catalase, and glutathione peroxidase support the fact that emblica
      application promotes antioxidant activity at the wound site. In summary, this
      study provides firm evidence to support that topical application of emblica
      represents a feasible and productive approach to support dermal wound healing.

PMID- 19152657
TI  - Impaired cutaneous wound healing in mice lacking tetranectin.
AB  - Tetranectin was originally purified from human serum on the basis of plasminogen
      kringle 4-binding properties. Tetranectin enhances plasminogen activation by a
      tissue-type plasminogen activator so that it has been suggested to play a role in
      tissue remodeling. We have generated mice with a targeted disruption of the
      tetranectin gene to elucidate the biological function of tetranectin. In this
      study, we showed that wound healing was markedly delayed in tetranectin-null mice
      compared with wild-type mice. A single full-thickness incision was made in the
      dorsal skin. By 14 days after the incision, the wounds fully healed in all wild
      type mice based on the macroscopic closure; in contrast, the progress of wound
      healing in the tetranectin null mice appeared to be impaired. In histological
      analysis, wounds of wild-type mice showed complete reepithelialization and healed
      by 14 days after the incision. However, those of tetranectin-null mice never
      showed complete reepithelialization at 14 days. At 21 days after the injury, the
      wound healed and was covered with an epidermis. These results supported the fact
      that tetranectin may play a role in the wound healing process.

PMID- 19152658
TI  - Depth of penetration of negative pressure wound therapy into underlying tissues.
AB  - Negative pressure wound therapy has become ubiquitous in orthopedic surgery and
      it is therefore important to understand the physiologic conditions of this
      therapy. The purpose of this study was to determine the magnitude and depth of
      negative pressure transmission into underlying muscle tissue in a wound model. We
      hypothesized that the negative pressure is not transmitted beyond 2 mm into
      underlying muscle tissue. Using both an isolated muscle and a live animal wound
      model, we applied open cell foam dressing to the tissue. Using a series of vacuum
      assisted closure negative pressure settings (0, -75, -125, -200 mmHg)
      interstitial fluid pressure was measured in the underlying tissue with a solid
      state pressure transducer catheter at 1/10 mm depth intervals. In the ex vivo
      isolated-muscle model, the effect of negative pressure wound therapy on
      interstitial fluid pressure was extinguished and not significantly different than
      controls at a depth <2 mm. In the live animal wound model, the magnitude of
      interstitial fluid pressures corresponded directly with negative pressure
      settings (p<0.01) and inversely with depth into muscle (p<0.01). Interstitial
      fluid pressures were significantly (p<0.05) less than control interstitial fluid
      pressures (0 mmHg setting) at depths of 0.5, 0.4, and 0.9 mm below the
      foam/muscle interface when the applied pressures were -75, -125, and -200 mmHg,
      respectively. Negative pressure wound therapy penetrates no more than 1 mm into
      rabbit wound tissue at the highest negative pressure setting (-200 mmHg) when
      using open-cell foam dressing.

PMID- 19152659
TI  - FGF-10 and specific structural elements of dermatan sulfate size and sulfation
      promote maximal keratinocyte migration and cellular proliferation.
AB  - Fibroblast growth factor-10 (FGF-10) is essential for epithelial development,
      while other members of this family, such as FGF-7, are not. FGF-10 is abundantly
      released into wounds following injury, and likely an essential growth factor
      required for this process. To evaluate how activation of this growth factor is
      controlled, multiple glycosaminoglycans were combined with FGF-10 assayed by
      measurement of the proliferation of cell lines expressing FGF receptor-2-IIIb, or
      keratinocyte migration in an in vitro wound repair assay. Dermatan sulfate (DS)
      exhibited greater potency than heparan sulfate or other chondroitin sulfates
      found in wounds. Structural variants of DS between 10 and 20 disaccharides
      containing iduronic acid showed maximal capacity to enable FGF-10 receptor
      stimulation. Furthermore, FGF-10 and DS markedly enhanced migration of
      keratinocytes in an in vitro wound scratch assay, while FGF-7 or other
      glycosaminoglycans did not. These data strongly suggest that FGF-10 activity is
      uniquely important in wound repair and that specific DS structural properties are
      necessary to promote FGF-10 function. These observations identify a novel
      interplay between DS and FGF-10 in mediating wound repair.

PMID- 19152660
TI  - A novel cell-adhesive scaffold material for delivering keratinocytes reduces
      granulation tissue in dermal wounds.
AB  - Novel peptide-conjugated chitosan membranes were fabricated and used to deliver
      keratinocytes to dermal wounds in mice. Three active peptides of 12 or 13 amino
      acids each, RLVSYNGIIFFLK (A5G27), ASKAIQVFLLAG (A5G33), and AGTFALRGDNPQG (A99)
      were selected from a cell-adhesive peptide library of laminin, a major
      constituent of basement membrane. The peptides were synthesized and coupled to
      chitosan membranes, and the resulting peptide-chitosan membranes were tested for
      keratinocyte attachment. Two of the peptides that bind to cell surface heparin
      like receptors (A5G27 and A5G33) were found to promote strong keratinocyte
      attachment, whereas the one that binds to integrin (A99) was inactive.
      Subsequently, A5G27- and A5G33-chitosan membranes were tested as vehicles for
      keratinocyte delivery in a wound model. We found that keratinocytes were
      delivered into the full-thickness wound with either membrane. Using the A5G33
      chitosan membrane, we further evaluated the activity of the delivered
      keratinocytes in wound healing. Immunohistochemistry for granulation tissue
      markers, including tenascin and alpha-smooth muscle actin, showed that
      keratinocyte delivery by the present peptide-chitosan membranes in the wound bed
      provided a favorable condition for keratinocyte migration along the wound surface
      and reduced granulation tissue formation.

PMID- 19152661
TI  - Tissue engineering a model for the human ear: assessment of size, shape,
      morphology, and gene expression following seeding of different chondrocytes.
AB  - This study examines the tissue engineering of a human ear model through use of
      bovine chondrocytes isolated from four different cartilaginous sites (nasoseptal,
      articular, costal, and auricular) and seeded onto biodegradable poly(l-lactic
      acid) and poly(L-lactide-epsilon-caprolactone) (50 : 50) polymer ear-shaped
      scaffolds. After implantation in athymic mice for up to 40 weeks, cell/scaffold
      constructs were harvested and analyzed in terms of size, shape, histology, and
      gene expression. Gross morphology revealed that all the tissue-engineered
      cartilages retained the initial human auricular shape through 40 weeks of
      implantation. Scaffolds alone lost significant size and shape over the same
      period. Quantitative reverse transcription-polymerase chain reaction demonstrated
      that the engineered chondrocyte/scaffolds yielded unique expression patterns for
      type II collagen, aggrecan, and bone sialoprotein mRNA. Histological analysis
      showed type II collagen and proteoglycan to be the predominant extracellular
      matrix components of the various constructs sampled at different implantation
      times. Elastin was also present but it was found only in constructs seeded with
      auricular chondrocytes. By 40 weeks of implantation, tissue-engineered cartilage
      of costal origin became calcified, marked by a notably high relative gene
      expression level of bone sialoprotein and the presence of rigid, nodular
      protrusions formed by mineralizing rudimentary cartilaginous growth plates. The
      collective data suggest that nasoseptal, articular, and auricular cartilages
      represent harvest sites suitable for development of tissue-engineered human ear
      models with retention over time of three-dimensional construct architecture, gene
      expression, and extracellular matrix composition comparable to normal,
      nonmineralizing cartilages. Calcification of constructs of costal chondrocyte
      origin clearly shows that chondrocytes from different tissue sources are not
      identical and retain distinct characteristics and that these specific cells are
      inappropriate for use in engineering a flexible ear model.

PMID- 19152663
TI  - Development of a recombinant antigen-based ELISA for the sero-detection of
      porcine lymphotropic herpesviruses.
AB  - BACKGROUND: Xenotransplantation using pigs as donor species carries a risk for
      the activation of latent porcine herpesviruses and potential transmission to the
      human recipient. The porcine lymphotropic herpesviruses (PLHV-1, -2, -3) are
      widespread in domestic pigs and closely related to the human gammaherpesviruses,
      Epstein-Barr virus and Kaposi sarcoma herpesvirus, causing lymphoproliferative
      disorders. PLHV-1 has been associated with a porcine post-transplantation
      lymphoproliferative disorder (PTLD), affecting miniature swine after experimental
      transplantation. In human xenotransplantation, PLHV might be transferred to the
      transplant recipient and cause PTLD or related diseases. The elimination of PLHV
      from donor pigs is therefore necessary, and requires the availability of nucleic
      acid- and antibody-based detection methods. METHODS: The N- and C-terminal parts
      (gB1 and gB2) of the glycoprotein B gene of PLHV-1, -2 and -3 were cloned and
      expressed in Escherichia coli. Antisera were raised in mice. PLHV PCR was
      performed as published earlier. RESULTS: An ELISA was developed, using
      recombinant glycoprotein B of PLHV-1 as the antigen, and used for the analysis of
      groups of pigs, differing by age and origin. Seropositivity ranged from 38%
      (piglets) to 90% (gilts) and 100% (breeding sows, miniature pigs and pigs for
      slaughter). In comparison, PCR products of PLHV were found in the blood of 0 to
      80% of the pig groups. Additionally, a group of 12 piglets was tested repeatedly
      after birth until the age of 156 days. A decline of antibodies was found during
      the first 3 weeks after birth, followed by a rise in most pigs during the weeks
      thereafter. PLHV PCR products in the blood were only observed later than 3 weeks
      after birth. CONCLUSION: Newborn pigs may be passively protected by maternal
      antibodies against PLHV infection during the first 3 weeks post partum. The rise
      of antibody titers thereafter and the appearance of PLHV sequences in the blood
      possibly indicates de novo infection by contact to the infected mother sow. The
      PLHV-ELISA may aid in breeding PLHV-free pigs.

PMID- 19152664
TI  - Differential human serum-mediated neutralization of PERV released from pig cells
      transfected with variants of hDAF.
AB  - BACKGROUND: Expression of complement regulatory proteins (CRP) on pig endothelial
      cells (PEC) is an effective means of avoiding induction of hyperacute rejection
      by human sera. However, pig endogenous retrovirus (PERV) from PEC transfected
      with CRP may acquire resistance to human sera. This study investigated a form of
      transfected CRP that is easily expressed on PERV particles. METHODS: The PEC line
      was transfected with the Lac Z gene and PERV-B to investigate PERV infectivity
      using a Lac Z pseudo-type assay. The cDNAs of several modified DAF (CD55) were
      then transfected into the PEC(Lac Z)/P-B lines using lipofection. DAF expression
      was verified by FACS analysis. Complement-dependent PEC lysis was tested to
      verify the complement regulatory function of the expressed DAF. HEK293 cells were
      incubated with PEC culture supernatants with or without human sera. The
      inoculated 293 cells were histochemically stained and Lac Z-positive blue foci
      were counted. The rate of reduction in Lac Z-positive cells resulting from the
      addition of human serum was then calculated. In addition, to assess the
      localization of the expressed DAF, flotation sucrose density analysis was
      performed. RESULTS: While PERV released from PEC expressing delta-short consensus
      repeat 2 (delta-SCR2) DAF (lacking CRP function) showed no change in resistance
      to human serum compared to control cells, PERV from cells expressing delta-SCR1
      DAF (with CRP function) showed a significant increase in resistance. The DAF
      blocking antibody assay indicated that PERV from the DAF transfectants expressed
      DAF molecules on the surface of the retrovirus. While delta-SCR1 DAF (PI-anchor
      form) significantly inhibited the reduction of Lac Z-positive cells by human
      serum, the reduction of Lac Z-positive cells by human serum was less inhibited in
      the case of transmembrane (TM)-types of DAF-HLA-G, modified influenza
      hemagglutinin (HA) and MCP (delta-CYT form). However, the reduction in each TM
      type DAF was slightly less than that observed in naive and mock cells. The
      flotation sucrose density analysis of these transfectants indicated that the PI
      anchor form of DAF is a raft-associated protein, and most TM-types of DAF are non
      raft proteins. CONCLUSION: Induction of resistance to human serum in PERV,
      depends on the form of the CRP tail. The CRP/TM hybrid that does not associate
      with lipid rafts, is a suitable form of CRP for gene transduction.

PMID- 19152665
TI  - Experimental application of xenogenous antlerogenic cells in replacement of
      auricular cartilage in rabbits.
AB  - BACKGROUND: Regenerative medicine in the recent years aims at explaining
      involvement of stem cells in regenerative processes and applying this knowledge
      in fulfilling human needs to find new, more efficient therapeutic methods.
      Growing antlers constitute a model organ for examining regeneration processes of
      tissues because they are the only mammalian appendages capable of regeneration.
      The rate of growth of deer antlers makes them one of the quickest growing
      structures in mammals. The cells taking part in this process have a considerable
      proliferating potential. The aim of the study was to analyze the possibility of
      using xenogenous antlerogenic cells (AC) in regeneration of cartilaginous tissues
      in non-immunosuppressed animals. METHODS: We undertook to use a xenogenous
      implant consisting of cultured antlerogenic mesenchymal cells suspended in
      hemostatic sponge in the reconstruction of lesions of ear cartilage in nine
      rabbits. A surgical site was prepared half-way up the outer, dorsal part of the
      right ear. About 1 cm from the free edge of the ear, a centrally peduncled flap
      of skin and perichondrium was prepared, measuring 1.5 cm x 1.5 cm. The exposed
      cartilage was excised in an area of about 1 cm x 1 cm. In the operated rabbits,
      in the prepared perichondrial pocket, we placed a flake of Spongostan saturated
      with the suspension of AC. Xenogenous cell survival and regeneration abilities
      were determined by histologic, immunohistochemical, and electron microscopy
      analysis of the grafts. RESULTS: In each case, healing occurred properly and
      neither local inflammation, necrosis nor implant rejection was observed. The
      hyaline cartilage lesion was replaced by new fibrous cartilage. This is similar
      to the histologic process occurring in growing deer antlers. The histologic,
      immunohistochemical, and electron microscopy analysis demonstrated the presence
      (and thus possible participation) of exogenous cells in the reconstructive
      process. At the same time, the immune response was very weak, which was confirmed
      by immunohistochemical reactions. CONCLUSION: Implanted antlerogenic cells were
      not rejected and possibly took part in the reconstruction of missing sections of
      the scaffolding of the rabbits' ear cartilages (although the mechanism is yet
      unknown). Low immunogenicity of AC, simplicity, efficiency, and low costs of
      production of implant material are the benefits of this method. Further research
      should unequivocally answer the question whether the MIC-1 cells are or are not
      the long-sought-after ideal material for the reconstruction of cartilaginous
      tissue lesions in various species, including human.

PMID- 19152666
TI  - Biomechanical properties of ascending aorta and pulmonary trunk in pigs and
      humans.
AB  - BACKGROUND: This study aims to obtain the biomechanical properties of ascending
      aorta and pulmonary trunk between healthy humans and pigs of different months, so
      as to provide necessary biomechanical experimental basis for anastomosing blood
      vessel in pig-to-human heart xenotransplantation. METHODS: Ascending aorta and
      pulmonary trunks of the six deceased donors (male 4, female 2) and 42 Chinese
      Hubei white pigs aged 1-7 months were performed biomechanical test. The blood
      vessel was given periodic permanent loading and unloading, and repeated force
      deformation data were obtained. The elastic properties of the blood vessels were
      obtained by curve from experimental data. RESULTS: The biomechanical material
      constant of ascending aorta and pulmonary trunk of pigs did not increase with the
      increase of age (F = 14.569, P = 0.126). The biomechanical material constant of
      humans was basically similar to that of pigs aged 1-7 months (F = 12.264, P =
      0.225). The elastic modulus was the biggest in pigs aged 7 months in comparison
      with that in other ages (F = 27.425, P = 0.032). There was no significant
      difference of elastic modulus of corresponding blood vessel between humans and
      pigs of different months (F = 17.328, P = 0.215). CONCLUSIONS: Our present study
      suggests that there was no significant difference of elastic properties of
      ascending aorta and pulmonary trunks between humans and pigs. From biomechanical
      aspects, anastomosis of corresponding ascending aorta and pulmonary trunks in the
      process of pig-to-human heart xenotransplantation may be feasible.

PMID- 19152667
TI  - Assignment of the SLA alleles and reproductive potential of selective breeding
      Duroc pig lines.
AB  - BACKGROUND: Pigs with defined swine leukocyte antigen (SLA) haplotypes and their
      detailed information are useful for transplantation and immunological studies. We
      developed two herds of SLA homozygous Duroc pigs with novel SLA haplotypes and
      characterized their reproductive potential. METHODS: For selective inbreeding, a
      pair of Duroc pigs was chosen as initial breeders, and substantial breeding
      within progenies was carried out for eight generations. In the selective breeding
      Duroc pigs, SLA haplotypes were assigned by nucleotide sequence determination of
      reverse transcription polymerase chain reaction (RT-PCR) products of three SLA
      classical class I genes and two class II genes. Based on this sequence
      information, we developed a rapid and simple SLA class II DNA typing method by
      polymerase chain reaction-sequence specific primer (PCR-SSP) technique. As a
      complementary method for the characterization of the SLA haplotypes, genetic
      polymorphisms of 36 microsatellite (MS) markers within the SLA region were also
      analyzed in the selective breeding pigs with SLA homozygous/heterozygous
      haplotypes. RESULTS: Among the selective breeding pigs from the third to fifth
      generations, only two SLA haplotypes were identified by the RT-PCR based SLA
      typing method; Hp-27.30 (SLA-1*08an03, SLA-1*06an04, SLA-2*0102, SLA-3*0101
      DRB1*1101 and DQB1*0503) and Hp-60.13 (SLA-1*an02, SLA-2*1002, SLA-3*0502,
      DRB1*0403 and DQB1*0303). In these two SLA haplotypes, two class I haplotypes, Hp
      27.0 and Hp-60.0, are novel. Furthermore, two class II haplotypes, Hp-0.30 and Hp
      0.13, which were previously reported in Korean native pigs and pigs of Hanford
      breed, respectively, were also assigned by a simple assay using a PCR-SSP
      technique in the entire selective breeding stock. Moreover, two haplotype
      specific MS patterns were observed across the entire SLA region in the selective
      breeding (homozygous/heterozygous) pigs. No morphological abnormalities were
      observed in selective breeding pigs. The theoretical inbreeding coefficient at
      the eighth generation was 78.5%. In all generations of selective breeding pigs,
      litter sizes were comparable and weaning weights from the fifth to eighth
      generation produced progenies significantly lighter (P < 0.01) than those in the
      non-selective breeding pigs. CONCLUSIONS: We established and characterized SLA
      homozygous Duroc herds with two kinds of haplotypes that can be used as a new
      resource for transplantation and other biomedical studies.

PMID- 19152668
TI  - Immunologic analyses of bovine bone treated with a novel tissue sterilization
      process.
AB  - BACKGROUND: This study evaluates the efficacy of removal of xeno-antigens from
      bovine bone using a patented BioCleanse process for decellularization of
      allograft tissues for clinical implantation. BioCleanse deploys a combination of
      chemicals and several high pressure rinses to achieve standardized sterility
      assurance levels. This method produces sterile grafts without reducing allograft
      bone biomechanical properties and effectively removes cells, lipids, and other
      sources of antigenic material from human allografts for clinical use. METHODS: In
      this investigation, BioCleanse is evaluated for its potential in removing
      xenograft antigens from bovine bone grafts followed by immunologic evaluation in
      the subcutaneous pouch of immunocompetent rats. The alpha-galactosyl (alpha-gal)
      epitope with the structure Galalpha1-3Galbeta1-4GlcNAc-R constitutes a critical
      component of xenoantigens and its removal using BioCleanse from bovine bone was
      compared with tissue levels of unprocessed bone. The relative degree of antigen
      removal was also determined through measuring the pro-inflammatory cytokine,
      tumor necrosis factor (TNF)-alpha, and through the use of histologic grading of
      cellular infiltrates into bone. RESULTS: Compact cortical bone inhibited immune
      cell migration but cancellous bone demonstrated cellular increase and bone
      resorption in the untreated control group. The alpha-gal xenoantigen level was
      significantly lower in both cortical (P < 0.001) and cancellous bone (P < 0.001)
      compared with controls. TNF-alpha levels were significantly (P < 0.001) reduced
      compared with untreated controls when human acute monocytic leukemia cells were
      exposed to cortical or cancellous bone. CONCLUSIONS: BioCleanse effectively
      removed xenoantigens and inflammatory markers justifying a follow up study in
      primates to determine these benefits in a model that is primed with preformed
      xeno-antibodies responsible for hyperacute rejection in hard tissues.

PMID- 19152669
TI  - Chitosan/gelatin hydrogel as immunoisolative matrix for injectable bioartificial
      pancreas.
AB  - BACKGROUND: The feasibility of using chitosan/gelatin hydrogel as immunoisolative
      matrix to provide an additional protection to the microencapsulated islet cells
      was demonstrated in this study. We hope that the use of hydrogel can extend the
      functional longevity of microencapsulated islet cells during xenotransplantation.
      METHODS: Chitosan/gelatin solution with glycerol 2-phosphate disodium salt
      hydrate was prepared and utilized as a cell carrier. The biocompatibility of the
      chitosan/gelatin hydrogel was first established by using a mouse insulinoma cell
      line, NIT-1. Insulinoma cells were encapsulated in agarose as microspheres and
      then macroencapsulated in chitosan/gelatin hydrogel. In vitro cell activity,
      material-mediated cytotoxicity, cytokine-mediated cytotoxicity assay, and insulin
      secreting profiles of insulinoma/agarose microspheres macroencapsulated in
      chitosan/gelatin hydrogel were analyzed. For in vivo study, insulinoma/agarose
      microspheres with chitosan/gelatin solution was applied as an injectable
      bioartificial pancreas (BAPs). Insulinoma/agarose microspheres suspended in
      phosphate-buffered saline or in chitosan/gelatin solution was injected into the
      subcutaneous layer of diabetic rats. Non-fasting blood glucose (NFBG)
      concentration of rat was measured perioperatively. After pre-determined
      intervals, the chitosan/gelatin hydrogel containing insulinoma/agarose
      microspheres was retrieved for histologic examinations. RESULTS:
      Insulinoma/agarose microspheres macroencapsulated in hydrogel revealed functional
      activity and secreted insulin continually for 60 days in vitro. Chitosan/gelatin
      hydrogel was not cytotoxic to islet cells, and in contrast, the hydrogel showed
      cytoprotective effects against cytokine-mediated cytotoxicity. The NFBG of
      diabetic rats transplanted with free insulinoma/agarose microspheres was
      decreased to euglycemia but restored to hyperglycemia in 15 days. Contrarily, the
      NFBG of rats transplanted with insulinoma/agarose microspheres with hydrogel
      remained euglycemic for 42 days. Histologic sections revealed that the fibrous
      tissue envelopment and the infiltrated immune-related cells contributed to the
      dysfunction of BAPs. CONCLUSIONS: This study indicates that using
      chitosan/gelatin hydrogel as a cell carrier is feasible and can provide an
      additional protection for the microencapsulated islet cells during
      xenotransplantation.

PMID- 19152670
TI  - Xenotransplantation literature update: September-October 2008.

PMID- 19152674
TI  - Validation of previously identified serum biomarkers for breast cancer with SELDI
      TOF MS: a case control study.
AB  - BACKGROUND: Serum protein profiling seems promising for early detection of breast
      cancer. However, the approach is also criticized, partly because of difficulties
      in validating discriminatory proteins. This study's aim is to validate three
      proteins previously reported to be discriminative between breast cancer cases and
      healthy controls. These proteins had been identified as a fragment of inter-alpha
      trypsin inhibitor H4 (4.3 kDa), C-terminal-truncated form of C3a des arginine
      anaphylatoxin (8.1 kDa) and C3a des arginine anaphylatoxin (8.9 kDa). METHODS:
      Serum protein profiles of 48 breast cancer patients and 48 healthy controls were
      analyzed with surface-enhanced laser desorption/ionization time-of-flight mass
      spectrometry (SELDI-TOF MS). Differences in protein intensity between breast
      cancer cases and controls were measured with the Mann-Whitney U test and adjusted
      for confounding in a multivariate logistic regression model. RESULTS: Four peaks,
      with mass-to-charge ratio (m/z) 4276, 4292, 8129 and 8941, were found that were
      assumed to represent the previously reported proteins. M/z 4276 and 4292 were
      statistically significantly decreased in breast cancer cases compared to healthy
      controls (p < 0.001). M/z 8941 was decreased in breast cancer cases (p < 0.001)
      and m/z 8129 was not related with breast cancer (p = 0.87). Adjustment for sample
      preparation day, sample storage duration and age did not substantially alter
      results. CONCLUSION: M/z 4276 and 4292 both represented the previously reported
      4.3 kDa protein and were both decreased in breast cancer patients, which is in
      accordance with the results of most previous studies. M/z 8129 was in contrast
      with previous studies not related with breast cancer. Remarkably, m/z 8941 was
      decreased in breast cancer cases whereas in previous studies it was increased.
      Differences in patient populations and pre-analytical sample handling could have
      contributed to discrepancies. Further research is needed before we can conclude
      on the relevance of these proteins as breast cancer biomarkers.

PMID- 19152675
TI  - Older cancer patients' information and support needs surrounding treatment: An
      evaluation through the eyes of patients, relatives and professionals.
AB  - BACKGROUND: Providing cancer patients with adequate treatment information is
      important for patients' health, well-being and satisfaction. Nurses play an
      important role in patient education. So far, few studies focused on the specific
      information needs of older cancer patients surrounding chemotherapy treatment.
      Given the growing incidence of cancer among older individuals, insight in these
      needs is crucial. This article describes the views of older cancer patients,
      their relatives and professionals on older patients' specific communication needs
      regarding chemotherapy treatment. METHODS: A qualitative design was used. Five
      focus group interviews were held with older cancer patients and their partners
      (two groups) and professionals with a background in nursing, oncology,
      gerontology and/or patient-provider communication (three groups). In addition,
      face to face in-depth interviews were conducted with older cancer patients. A
      total number of 38 patients and relatives participated, with a mean age of 67.6
      years. The focus groups and interviews were audio-recorded for subsequent
      transcription and analysis. RESULTS: Older people have more difficulties
      processing and remembering information than younger ones. A trustful environment
      appears to be a prerequisite for reflection of older patients on the information
      provided and individualized information is essential to enhance memory of
      information. However, the results show that both patients and professionals
      experienced insufficient exploration of the patients' personal situation and
      individual information needs. Patients also strengthened the importance of
      sensitive communication, e.g. showing empathy en emotional support, throughout
      the continuum of cancer care. Moreover, potential areas of improvement were
      identified, including engaging the patients' relatives and encouraging patients
      and relatives to ask questions. CONCLUSION: Patient education should be more
      tailored to older cancer patients' individual information and support needs and
      abilities by exploring the required amount and content of information, treatment
      goals and expectations. Nurses can establish a trustful environment by showing
      empathy and emotional support. Recommendations are given to enhance recall of
      information in older patients; information giving should be more structured by
      summarizing and repeating the most important, personally relevant information. To
      adapt to specific information needs, communication training for nurses and the
      use of aids such as a question prompt sheet could be useful tools.

PMID- 19152676
TI  - Seasonal variance of 25-(OH) vitamin D in the general population of Estonia, a
      Northern European country.
AB  - BACKGROUND: Vitamin D has a wide variety of physiological functions in the human
      body. There is increasing evidence that low serum levels of this vitamin have an
      important role in the pathogenesis of different skeletal and extra-skeletal
      diseases. Vitamin D deficiency and insufficiency is common at northern latitudes.
      There are few population-based studies in the northern European region looking at
      the issue in a wider age group. We aimed to measure Vitamin D level in the
      general population of Estonia (latitude 59 degrees N), a North-European country
      where dairy products are not fortified with vitamin D. METHODS: The study
      subjects were a population-based random selection of 367 individuals (200 women
      and 167 men, mean age 48.9 +/- 12.2 years, range 25-70 years) from the registers
      of general health care providers. 25-(OH) vitamin D (25(OH)D) level and
      parathyroid hormone (PTH) were measured in summer and in winter. Additionally
      age, sex, body mass index (BMI) and self-reported sunbathing habits were
      recorded. RESULTS: The mean serum 25(OH)D concentration in winter was 43.7 +/- 15
      nmol/L and in summer 59.3 +/- 18 nmol/L (p < 0.0001). In winter 73% of the
      subjects had 25(OH)D insufficiency (25(OH)D concentration below 50 nmol/L) and 8%
      had deficiency (25(OH)D below 25 nmol/L). The corresponding percentages in summer
      were 29% for insufficiency and less than 1% for deficiency. PTH reached a plateau
      at around 80 nmol/L. BMI and age were inversely associated with 25(OH)D, but lost
      significance when adjusted for sunbathing habits. A difference in the seasonal
      25(OH)D amplitude between genders (p = 0.01) was revealed. CONCLUSION: Vitamin D
      insufficiency is highly prevalent throughout the year in a population without
      vitamin D dairy fortification living at the latitude of 59 degrees N.

PMID- 19152677
TI  - Evaluation of a microarray-hybridization based method applicable for discovery of
      single nucleotide polymorphisms (SNPs) in the Pseudomonas aeruginosa genome.
AB  - BACKGROUND: Whole genome sequencing techniques have added a new dimension to
      studies on bacterial adaptation, evolution and diversity in chronic infections.
      By using this powerful approach it was demonstrated that Pseudomonas aeruginosa
      undergoes intense genetic adaptation processes, crucial in the development of
      persistent disease. The challenge ahead is to identify universal infection
      relevant adaptive bacterial traits as potential targets for the development of
      alternative treatment strategies. RESULTS: We developed a microarray-based method
      applicable for discovery of single nucleotide polymorphisms (SNPs) in P.
      aeruginosa as an easy and economical alternative to whole genome sequencing.
      About 50% of all SNPs theoretically covered by the array could be detected in a
      comparative hybridization of PAO1 and PA14 genomes at high specificity (> 0.996).
      Variations larger than SNPs were detected at much higher sensitivities, reaching
      nearly 100% for genetic differences affecting multiple consecutive probe
      oligonucleotides. The detailed comparison of the in silico alignment with
      experimental hybridization data lead to the identification of various factors
      influencing sensitivity and specificity in SNP detection and to the
      identification of strain specific features such as a large deletion within the
      PA4684 and PA4685 genes in the Washington Genome Center PAO1. CONCLUSION: The
      application of the genome array as a tool to identify adaptive mutations, to
      depict genome organizations, and to identify global regulons by the "ChIP-on
      chip" technique will expand our knowledge on P. aeruginosa adaptation, evolution
      and regulatory mechanisms of persistence on a global scale and thus advance the
      development of effective therapies to overcome persistent disease.

PMID- 19152678
TI  - Valsalva maneuver, uncontrolled hypertension, asymmetric septal hypertrophy and
      dynamic outflow obstruction: a case report.
AB  - A 83-year-old woman presented with a 25-year history of hypertension which was
      long-standing, uncontrolled, severe hypertension because of irregular oral
      administration of antihypertensive drug underwent an echocardiographic
      examination as part of an evaluation of hypertension. She described chest
      distress associated with activity, syncope for three times in the past one year.
      On physical examination, she was in no acute distress, with a regular pulse rate
      and blood pressure of 185/115 mmHg. On auscultation, her lung fields were clear.
      There was a III/VI late peaking crescendo/decrescendo systolic murmur along the
      left sternal border radiating to the apex, which increased with standing and
      Valsalva's maneuver and decreased with squatting. There was no report of
      provocative maneuvers performed during auscultation. There was no edema.
      Transthoracic echocardiography showed a hyperdynamic left ventricle with markedly
      increased left ventricular wall thicknesses and asymmetrical septal hypertrophy.
      M-mode echocardiography showed systolic anterior motion of the mitral valve
      apparatus and midsystolic closure of the aortic valve. A dynamic left ventricular
      outflow tract obstruction was present, with a resting maximal instantaneous
      gradient of 55 mmHg. With the Valsalva maneuver, the gradient increased to 114
      mmHg. No any factors that could cause hypertension were found at kidney, adrenal
      gland and renal artery etc. by ultrasound and multislice compute tomography.

PMID- 19152679
TI  - A universal assay for detection of oncogenic fusion transcripts by oligo
      microarray analysis.
AB  - BACKGROUND: The ability to detect neoplasia-specific fusion genes is important
      not only in cancer research, but also increasingly in clinical settings to ensure
      that correct diagnosis is made and the optimal treatment is chosen. However, the
      available methodologies to detect such fusions all have their distinct short
      comings. RESULTS: We describe a novel oligonucleotide microarray strategy whereby
      one can screen for all known oncogenic fusion transcripts in a single experiment.
      To accomplish this, we combine measurements of chimeric transcript junctions with
      exon-wise measurements of individual fusion partners. To demonstrate the
      usefulness of the approach, we designed a DNA microarray containing 68,861
      oligonucleotide probes that includes oligos covering all combinations of chimeric
      exon-exon junctions from 275 pairs of fusion genes, as well as sets of oligos
      internal to all the exons of the fusion partners. Using this array, proof of
      principle was demonstrated by detection of known fusion genes (such as TCF3:PBX1,
      ETV6:RUNX1, and TMPRSS2:ERG) from all six positive controls consisting of
      leukemia cell lines and prostate cancer biopsies. CONCLUSION: This new method
      bears promise of an important complement to currently used diagnostic and
      research tools for the detection of fusion genes in neoplastic diseases.

PMID- 19152680
TI  - Expression of 5S rDNA in the oocytes of water frogs.
AB  - BACKGROUND: We report the expression pattern of 5S rDNA in the eggs of water
      frogs Rana lessonae, Rana ridibunda and Rana esculenta using the quantitative
      real-time PCR. This kind of research had never been performed before. RESULTS: 5S
      rDNA relative expression of the Rana ridibunda oocytes is approximately six times
      higher in comparison to the Rana lessonae oocytes. The oocytes of the
      investigated Rana esculenta frogs, in respect of 5S rDNA relative expression
      ratio, were very similar to the Rana ridibunda oocytes. CONCLUSION: We suggest
      the possibility of using 5S rDNA as the internal control gene, in the studies of
      relative mRNA quantitative assays in water frog oocytes, because of its
      characteristic specific expression pattern in the Rana lessonae, Rana ridibunda
      and Rana esculenta oocytes.

PMID- 19152681
TI  - The external validity of published randomized controlled trials in primary care.
AB  - BACKGROUND: A criticism of Randomized Controlled Trials (RCTs) in primary care is
      that they lack external validity, participants being unrepresentative of the
      wider population. Our aim was to determine whether published primary care-based
      RCTs report information about how the study sample is assembled, and whether this
      is associated with RCT characteristics. METHODS: We reviewed RCTs published in
      four primary care journals in the years 2001-2004. Main outcomes were: (1)
      eligibility fraction (proportion eligible of those screened), (2) enrolment
      fraction (proportion randomised of those eligible), (3) recruitment fraction
      (proportion of potential participants actually randomised), and (4) number of
      patients needed to be screened (NNS) in order to randomize one participant.
      RESULTS: A total of 148 RCTs were reviewed. One hundred and three trials (70%)
      reported the number of individuals assessed by investigators for eligibility, 119
      (80%) reported the number eligible for participation, and all reported the actual
      number recruited. The median eligibility fraction was 83% (IQR 40% to 100%), and
      the median enrolment fraction was 74% (IQR 49% to 92%). The median NNS was 2.43,
      with some trials reportedly recruiting every patient or practice screened for
      eligibility, and one trial screening 484 for each patient recruited. We found no
      association between NNS and journal, trial size, multi- or single-centre, funding
      source or type of intervention. There may be associations between provision of
      sufficient recruitment data for the calculation of NNS and funding source and
      type of intervention. CONCLUSION: RCTs reporting recruitment data in primary care
      suggest that once screened for eligibility and found to match inclusion criteria
      patients are likely to be randomized. This finding needs to be treated with
      caution as it may represent inadequate identification or reporting of the
      eligible population. A substantial minority of RCTs did not provide sufficient
      information about the patient recruitment process.

PMID- 19152682
TI  - Ethnic differences in cardiometabolic risk profile in an overweight/obese
      paediatric cohort in the Netherlands: a cross-sectional study.
AB  - BACKGROUND: Differences in prevalence of cardiometabolic risk factors between
      different ethnic groups are largely unknown. We determined the variation in
      cardiometabolic risk profile according to ethnicity in a cohort overweight/obese
      Dutch children. METHODS: An oral glucose tolerance test was performed in 516
      overweight/obese Dutch children of multi-ethnic origin, attending an obesity out
      patient clinic of an urban general hospital (mean age 10.6 +/- 3.2; 55.2% boys).
      Anthropometric parameters and blood samples were collected, and the prevalence of
      (components of) the metabolic syndrome (MetS) and insulin resistance were
      determined in each ethnic group. RESULTS: Major ethnic groups were Dutch native
      (18.4%), Turkish (28.1%), and Moroccan (25.8%). The remaining group (27.7%)
      consisted of children with other ethnicities. Turkish children had the highest
      mean standardized BMI compared to Dutch native children (P < 0.05). As compared
      to Moroccan children, they had a higher prevalence of MetS (22.8% vs. 12.8%), low
      HDL-cholesterol (37.9% vs. 25.8%), hypertension (29.7% vs. 18.0%) and insulin
      resistance (54.9% vs. 37.4%, all P < 0.05). Although Turkish children also had
      higher prevalences of forementioned risk factors than Dutch native children,
      these differences were not statistically significant. Insulin resistance was
      associated with MetS in the Turkish and Moroccan subgroup (OR 6.6; 95%CI, 2.4
      18.3 and OR 7.0; 95%CI, 2.1-23.1, respectively). CONCLUSION: In a Dutch cohort of
      overweight/obese children, Turkish children showed significantly higher
      prevalences of cardiometabolic risk factors relative to their peers of Moroccan
      descent. The prospective value of these findings needs to be established as this
      may warrant the need for differential ethnic-specific preventive measures.

PMID- 19152683
TI  - Identification and validation of clinical predictors for the risk of neurological
      involvement in children with hand, foot, and mouth disease in Sarawak.
AB  - BACKGROUND: Human enterovirus 71 (HEV71) can cause Hand, foot, and mouth disease
      (HFMD) with neurological complications, which may rapidly progress to fulminant
      cardiorespiratory failure, and death. Early recognition of children at risk is
      the key to reduce acute mortality and morbidity. METHODS: We examined data
      collected through a prospective clinical study of HFMD conducted between 2000 and
      2006 that included 3 distinct outbreaks of HEV71 to identify risk factors
      associated with neurological involvement in children with HFMD. RESULTS: Total
      duration of fever >or= 3 days, peak temperature >or= 38.5 degrees C and history
      of lethargy were identified as independent risk factors for neurological
      involvement (evident by CSF pleocytosis) in the analysis of 725 children admitted
      during the first phase of the study. When they were validated in the second phase
      of the study, two or more (>or= 2) risk factors were present in 162 (65%) of 250
      children with CSF pleocytosis compared with 56 (30%) of 186 children with no CSF
      pleocytosis (OR 4.27, 95% CI2.79-6.56, p < 0.0001). The usefulness of the three
      risk factors in identifying children with CSF pleocytosis on hospital admission
      during the second phase of the study was also tested. Peak temperature >or= 38.5
      degrees C and history of lethargy had the sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of 28%(48/174),
      89%(125/140), 76%(48/63) and 50%(125/251), respectively in predicting CSF
      pleocytosis in children that were seen within the first 2 days of febrile
      illness. For those presented on the 3rd or later day of febrile illness, the
      sensitivity, specificity, PPV and NPV of >or= 2 risk factors predictive of CSF
      pleocytosis were 75%(57/76), 59%(27/46), 75%(57/76) and 59%(27/46), respectively.
      CONCLUSION: Three readily elicited clinical risk factors were identified to help
      detect children at risk of neurological involvement. These risk factors may serve
      as a guide to clinicians to decide the need for hospitalization and further
      investigation, including cerebrospinal fluid examination, and close monitoring
      for disease progression in children with HFMD.

PMID- 19152684
TI  - Improved homology-driven computational validation of protein-protein interactions
      motivated by the evolutionary gene duplication and divergence hypothesis.
AB  - BACKGROUND: Protein-protein interaction (PPI) data sets generated by high
      throughput experiments are contaminated by large numbers of erroneous PPIs.
      Therefore, computational methods for PPI validation are necessary to improve the
      quality of such data sets. Against the background of the theory that most extant
      PPIs arose as a consequence of gene duplication, the sensitive search for
      homologous PPIs, i.e. for PPIs descending from a common ancestral PPI, should be
      a successful strategy for PPI validation. RESULTS: To validate an experimentally
      observed PPI, we combine FASTA and PSI-BLAST to perform a sensitive sequence
      based search for pairs of interacting homologous proteins within a large,
      integrated PPI database. A novel scoring scheme that incorporates both quality
      and quantity of all observed matches allows us (1) to consider also tentative
      paralogs and orthologs in this analysis and (2) to combine search results from
      more than one homology detection method. ROC curves illustrate the high efficacy
      of this approach and its improvement over other homology-based validation
      methods. CONCLUSION: New PPIs are primarily derived from preexisting PPIs and not
      invented de novo. Thus, the hallmark of true PPIs is the existence of homologous
      PPIs. The sensitive search for homologous PPIs within a large body of known PPIs
      is an efficient strategy to separate biologically relevant PPIs from the many
      spurious PPIs reported by high-throughput experiments.

PMID- 19152685
TI  - Transcriptomic and proteomic profiling of two porcine tissues using high
      throughput technologies.
AB  - BACKGROUND: The recent development within high-throughput technologies for
      expression profiling has allowed for parallel analysis of transcriptomes and
      proteomes in biological systems such as comparative analysis of transcript and
      protein levels of tissue regulated genes. Until now, such studies of have only
      included microarray or short length sequence tags for transcript profiling.
      Furthermore, most comparisons of transcript and protein levels have been based on
      absolute expression values from within the same tissue and not relative
      expression values based on tissue ratios. RESULTS: Presented here is a novel
      study of two porcine tissues based on integrative analysis of data from
      expression profiling of identical samples using cDNA microarray, 454-sequencing
      and iTRAQ-based proteomics. Sequence homology identified 2.541 unique transcripts
      that are detectable by both microarray hybridizations and 454-sequencing of 1.2
      million cDNA tags. Both transcript-based technologies showed high reproducibility
      between sample replicates of the same tissue, but the correlation across these
      two technologies was modest. Thousands of genes being differentially expressed
      were identified with microarray. Out of the 306 differentially expressed genes,
      identified by 454-sequencing, 198 (65%) were also found by microarray. The
      relationship between the regulation of transcript and protein levels was analyzed
      by integrating iTRAQ-based proteomics data. Protein expression ratios were
      determined for 354 genes, of which 148 could be mapped to both microarray and 454
      sequencing data. A comparison of the expression ratios from the three
      technologies revealed that differences in transcript and protein levels across
      heart and muscle tissues are positively correlated. CONCLUSION: We show that the
      reproducibility within cDNA microarray and 454-sequencing is high, but that the
      agreement across these two technologies is modest. We demonstrate that the
      regulation of transcript and protein levels across identical tissue samples is
      positively correlated when the tissue expression ratios are used for comparison.
      The results presented are of interest in systems biology research in terms of
      integration and analysis of high-throughput expression data from mammalian
      tissues.

PMID- 19152686
TI  - Determinants of mental health service use in the national mental health survey of
      the elderly in Singapore.
AB  - BACKGROUND: Despite high prevalence of mental health problems, only a minority of
      elderly people seek treatment. Although need-for-care factors are primary
      determinants of mental health service use, personal predisposing or enabling
      factors including health beliefs are important but are not well studied. METHOD:
      In the National Mental Health Survey of Elderly in Singapore, 2003, 1092 older
      adults aged 60 and above were interviewed for diagnosis of mental disorders
      (using Geriatric Mental State) and treatment, and their health beliefs about the
      curability of mental illness, embarrassment and stigma, easiness discussing
      mental problems, effectiveness and safety of treatment and trust in
      professionals. RESULTS: The prevalence of mental disorders was 13%, but only a
      third of mentally ill respondents had sought treatment. Increased likelihood of
      seeking treatment was significantly associated with the presence of a mental
      disorder (OR = 5.27), disability from mental illness (OR = 79.9), and poor or
      fair self-rated mental health (OR = 2.63), female gender (OR = 2.25), and formal
      education (OR = 2.40). The likelihood of treatment seeking was lower in those
      reporting financial limitations for medical care (OR = 0.38), but also higher
      household income (OR = 0.31). Negative beliefs showed no meaningful associations,
      but the positive belief that 'to a great extent mental illness can be cured' was
      associated with increased mental health service use (OR = 6.89). The availability
      of family caregiver showed a negative association (OR = 0.20). CONCLUSION: The
      determinants of mental health service use in the elderly included primary need
      factors, and female gender and socioeconomic factors. There was little evidence
      of influences by negative health beliefs, but a positive health belief that
      'mental illness can be cured' is a strongly positive determinant The influence of
      family members and care-givers on senior's use of mental health service should be
      further explored.

PMID- 19152687
TI  - Novel multicellular organotypic models of normal and malignant breast: tools for
      dissecting the role of the microenvironment in breast cancer progression.
AB  - INTRODUCTION: There is increasing recognition of the role of the microenvironment
      in the control of both normal and tumour cell behaviour. In the breast,
      myoepithelial cells and fibroblasts can influence tumour cell behaviour, with
      myoepithelial cells exhibiting a broad tumour-suppressor activity while
      fibroblasts frequently promote tumour growth and invasion. This study describes
      the development of physiologically relevant three-dimensional heterotypic culture
      systems containing mixed normal or tumour-derived breast populations and shows
      how such models can be used to dissect the interactions that influence cell
      behaviour. METHODS: Populations of luminal cells, myoepithelial cells and
      fibroblasts were isolated from normal and malignant breast tissue, characterised
      and compared with immortalised cell lines. Co-localisation of normal and
      malignant luminal cells with myoepithelial cells alone or with either normal or
      tumour-derived fibroblasts was studied. Cultures were grown for seven days, and
      then gels were fixed and whole gel immunofluorescence carried out to assess co
      localisation and polarisation. The potential role of matrix metalloproteinases
      (MMP) or hepatocyte growth factor(HGF)-c-met signalling in disrupting cellular
      organisation was investigated by incorporating inhibitors into cultures either
      alone or in combination. RESULTS: Over a culture period of seven days,
      myoepithelial cells organised themselves around luminal cell populations forming
      dual-cell co-units. Characterisation of co-units showed established basal
      polarity and differentiation analogous to their in vivo counterparts. Tumour cell
      co-units revealed subtle differences to normal co-units including disruption of
      basement membrane and loss of beta4-integrin, as described in ductal carcinoma in
      situ (DCIS) in vivo. Inclusion of normal fibroblasts had no influence on co-unit
      formation; however, inclusion of tumour-associated fibroblasts lead to disruption
      of co-unit organisation, and this was significantly inhibited in the presence of
      MMP and/or c-met inhibitors. CONCLUSIONS: To the best of the authors' knowledge,
      this study describes for the first time a co-culture model comprising three major
      components of normal and malignant breast: luminal cells, myoepithelial cells and
      stromal fibroblasts. These cells organise into structures recapitulating normal
      and DCIS breast, with homing of myoepithelial cells around the luminal
      population. Importantly, differences are exhibited between these systems
      reflecting those described in tissues, including a central role for tumour
      associated fibroblasts and MMPs in mediating disruption of normal structures.
      These findings support the value of these models in dissecting normal and tumour
      cell behaviour in an appropriate microenvironment.

PMID- 19152688
TI  - Global influences on milk purchasing in New Zealand--implications for health and
      inequalities.
AB  - BACKGROUND: Economic changes and policy reforms, consistent with economic
      globalization, in New Zealand in the mid-1980s, combined with the recent global
      demand for dairy products, particularly from countries undergoing a 'nutrition
      transition', have created an environment where a proportion of the New Zealand
      population is now experiencing financial difficulty purchasing milk. This
      situation has the potential to adversely affect health. DISCUSSION: Similar to
      other developed nations, widening income disparities and health inequalities have
      resulted from economic globalization in New Zealand; with regard to nutrition, a
      proportion of the population now faces food poverty. Further, rates of
      overweight/obesity and chronic diseases have increased in recent decades,
      primarily affecting indigenous people and lower socio-economic groups. Economic
      globalization in New Zealand has changed the domestic milk supply with regard to
      the consumer and may shed light on the link between globalization, nutrition and
      health outcomes. This paper describes the economic changes in New Zealand,
      specifically in the dairy market and discusses how these changes have the
      potential to create inequalities and adverse health outcomes. The implications
      for the success of current policy addressing chronic health outcomes is
      discussed, alternative policy options such as subsidies, price controls or
      alteration of taxation of recommended foods relative to 'unhealthy' foods are
      presented and the need for further research is considered. SUMMARY: Changes in
      economic ideology in New Zealand have altered the focus of policy development,
      from social to commercial. To achieve equity in health and improve access to
      social determinants of health, such as healthy nutrition, policy-makers must give
      consideration to health outcomes when developing and implementing economic
      policy, both national and global.

PMID- 19152689
TI  - Exercise and manual physiotherapy arthritis research trial (EMPART): a
      multicentre randomised controlled trial.
AB  - BACKGROUND: Osteoarthritis (OA) of the hip is a major cause of functional
      disability and reduced quality of life. Management options aim to reduce pain and
      improve or maintain physical functioning. Current evidence indicates that
      therapeutic exercise has a beneficial but short-term effect on pain and
      disability, with poor long-term benefit. The optimal content, duration and type
      of exercise are yet to be ascertained. There has been little scientific
      investigation into the effectiveness of manual therapy in hip OA. Only one
      randomized controlled trial (RCT) found greater improvements in patient-perceived
      improvement and physical function with manual therapy, compared to exercise
      therapy. METHODS AND DESIGN: An assessor-blind multicentre RCT will be undertaken
      to compare the effect of a combination of manual therapy and exercise therapy,
      exercise therapy only, and a waiting-list control on physical function in hip OA.
      One hundred and fifty people with a diagnosis of hip OA will be recruited and
      randomly allocated to one of 3 groups: exercise therapy, exercise therapy with
      manual therapy and a waiting-list control. Subjects in the intervention groups
      will attend physiotherapy for 6-8 sessions over 8 weeks. Those in the control
      group will remain on the waiting list until after this time and will then be re
      randomised to one of the two intervention groups. Outcome measures will include
      physical function (WOMAC), pain severity (numerical rating scale), patient
      perceived change (7-point Likert scale), quality of life (SF-36), mood (hospital
      anxiety and depression scale), patient satisfaction, physical activity (IPAQ) and
      physical measures of range of motion, 50-foot walk and repeated sit-to stand
      tests. DISCUSSION: This RCT will compare the effectiveness of the addition of
      manual therapy to exercise therapy to exercise therapy only and a waiting-list
      control in hip OA. A high quality methodology will be used in keeping with
      CONSORT guidelines. The results will contribute to the evidence base regarding
      the clinical efficacy for physiotherapy interventions in hip OA.

PMID- 19152690
TI  - Facts, values, and attention-deficit hyperactivity disorder (ADHD): an update on
      the controversies.
AB  - The Hastings Center, a bioethics research institute, is holding a series of 5
      workshops to examine the controversies surrounding the use of medication to treat
      emotional and behavioral disturbances in children. These workshops bring together
      clinicians, researchers, scholars, and advocates with diverse perspectives and
      from diverse fields. Our first commentary in CAPMH, which grew out of our first
      workshop, explained our method and explored the controversies in general. This
      commentary, which grows out of our second workshop, explains why informed people
      can disagree about ADHD diagnosis and treatment. Based on what workshop
      participants said and our understanding of the literature, we make 8 points. (1)
      The ADHD label is based on the interpretation of a heterogeneous set of symptoms
      that cause impairment. (2) Because symptoms and impairments are dimensional,
      there is an inevitable "zone of ambiguity," which reasonable people will
      interpret differently. (3) Many other variables, from different systems and tools
      of diagnosis to different parenting styles and expectations, also help explain
      why behaviors associated with ADHD can be interpreted differently. (4) Because
      people hold competing views about the proper goals of psychiatry and parenting,
      some people will be more, and others less, concerned about treating children in
      the zone of ambiguity. (5) To recognize that nature has written no bright line
      between impaired and unimpaired children, and that it is the responsibility of
      humans to choose who should receive a diagnosis, does not diminish the
      significance of ADHD. (6) Once ADHD is diagnosed, the facts surrounding the most
      effective treatment are complicated and incomplete; contrary to some popular
      wisdom, behavioral treatments, alone or in combination with low doses of
      medication, can be effective in the long-term reduction of core ADHD symptoms and
      at improving many aspects of overall functioning. (7) Especially when a child
      occupies the zone of ambiguity, different people will emphasize different values
      embedded in the pharmacological and behavioral approaches. (8) Truly informed
      decision-making requires that parents (and to the extent they are able, children)
      have some sense of the complicated and incomplete facts regarding the diagnosis
      and treatment of ADHD.

PMID- 19152691
TI  - Comparison of broad range 16S rDNA PCR and conventional blood culture for
      diagnosis of sepsis in the newborn: a case control study.
AB  - BACKGROUND: Early onset bacterial sepsis is a feared complication of the newborn.
      A large proportion of infants admitted to the Neonatal Intensive Care Unit (NICU)
      for suspected sepsis receive treatment with potent systemic antibiotics while a
      diagnostic workup is in progress. The gold standard for detecting bacterial
      sepsis is blood culture. However, as pathogens in blood cultures are only
      detected in approximately 25% of patients, the sensitivity of blood culture is
      suspected to be low. Therefore, the diagnosis of sepsis is often based on the
      development of clinical signs, in combination with laboratory tests such as a
      rise in C-reactive protein (CRP). Molecular assays for the detection of bacterial
      DNA in the blood represent possible new diagnostic tools for early identification
      of a bacterial cause. METHODS: A broad range 16S rDNA polymerase chain reaction
      (PCR) without preincubation was compared to conventional diagnostic work up for
      clinical sepsis, including BACTEC blood culture, for early determination of
      bacterial sepsis in the newborn. In addition, the relationship between known risk
      factors, clinical signs, and laboratory parameters considered in clinical sepsis
      in the newborn were explored. RESULTS: Forty-eight infants with suspected sepsis
      were included in this study. Thirty-one patients were diagnosed with sepsis, only
      6 of these had a positive blood culture. 16S rDNA PCR analysis of blinded blood
      samples from the 48 infants revealed 10 samples positive for the presence of
      bacterial DNA. PCR failed to be positive in 2 samples from blood culture positive
      infants, and was positive in 1 sample where a diagnosis of a non-septic condition
      was established. Compared to blood culture the diagnosis of bacterial proven
      sepsis by PCR revealed a 66.7% sensitivity, 87.5% specificity, 95.4% positive and
      75% negative predictive value. PCR combined with blood culture revealed bacteria
      in 35.1% of the patients diagnosed with sepsis. Irritability and feeding
      difficulties were the clinical signs most often observed in sepsis. CRP increased
      in the presence of bacterial infection. CONCLUSION: There is a need for PCR as a
      method to quickly point out the infants with sepsis. However, uncertainty about a
      bacterial cause of sepsis was not reduced by the PCR result, reflecting that
      methodological improvements are required in order for DNA detection to replace or
      supplement traditional blood culture in diagnosis of bacterial sepsis.

PMID- 19152692
TI  - Improved glycaemic control by switching from insulin NPH to insulin glargine: a
      retrospective observational study.
AB  - BACKGROUND: Insulin glargine (glargine) and insulin NPH (NPH) are two basal
      insulin treatments. This study investigated the effect on glycaemic control of
      switching from a NPH-based regimen to a glargine-based regimen in 701 patients
      with type 1 (n= 304) or type 2 (n= 397) diabetes, using unselected primary care
      data. METHODS: Data for this retrospective observational study were extracted
      from a UK primary care database (The Health Improvement Network). Patients were
      required to have at least 12 months of data before and after switching from NPH
      to glargine. The principal analysis was the change in HbA(1c) after 12 months
      treatment with glargine; secondary analyses included change in weight and total
      daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes
      reliable reporting of this outcome. Multivariate analyses were used to adjust for
      baseline characteristics and confounding variables. RESULTS: After adjustment,
      both diabetic cohorts showed statistically significant reductions in mean HbA(1c)
      12 months after the switch, by 0.38% (p < 0.001) in type 1 patients and 0.31% (p
      < 0.001) in type 2 patients. Improvement in HbA1c was positively correlated with
      baseline HbA(1c); patients with baseline HbA(1c) > or = 8% had reductions of
      0.57% (p < 0.001) and 0.47% (p < 0.001), respectively. There was no significant
      change in weight or total daily insulin dose while on glargine. The majority of
      patients received a basal-bolus regimen prior to and after the switch (mean 79.3%
      before and 77.2% after switch in type 1 patients, and 80.4% and 76.8%,
      respectively in type 2 patients, p > 0.05). CONCLUSION: In routine clinical
      practice, switching from NPH to glargine provides the opportunity for improving
      glycaemic control in diabetes patients inadequately controlled by NPH.

PMID- 19152693
TI  - Prediction of nuclear proteins using SVM and HMM models.
AB  - BACKGROUND: The nucleus, a highly organized organelle, plays important role in
      cellular homeostasis. The nuclear proteins are crucial for chromosomal
      maintenance/segregation, gene expression, RNA processing/export, and many other
      processes. Several methods have been developed for predicting the nuclear
      proteins in the past. The aim of the present study is to develop a new method for
      predicting nuclear proteins with higher accuracy. RESULTS: All modules were
      trained and tested on a non-redundant dataset and evaluated using five-fold cross
      validation technique. Firstly, Support Vector Machines (SVM) based modules have
      been developed using amino acid and dipeptide compositions and achieved a Mathews
      correlation coefficient (MCC) of 0.59 and 0.61 respectively. Secondly, we have
      developed SVM modules using split amino acid compositions (SAAC) and achieved the
      maximum MCC of 0.66. Thirdly, a hidden Markov model (HMM) based module/profile
      was developed for searching exclusively nuclear and non-nuclear domains in a
      protein. Finally, a hybrid module was developed by combining SVM module and HMM
      profile and achieved a MCC of 0.87 with an accuracy of 94.61%. This method
      performs better than the existing methods when evaluated on blind/independent
      datasets. Our method estimated 31.51%, 21.89%, 26.31%, 25.72% and 24.95% of the
      proteins as nuclear proteins in Saccharomyces cerevisiae, Caenorhabditis elegans,
      Drosophila melanogaster, mouse and human proteomes respectively. Based on the
      above modules, we have developed a web server NpPred for predicting nuclear
      proteins http://www.imtech.res.in/raghava/nppred/. CONCLUSION: This study
      describes a highly accurate method for predicting nuclear proteins. SVM module
      has been developed for the first time using SAAC for predicting nuclear proteins,
      where amino acid composition of N-terminus and the remaining protein were
      computed separately. In addition, our study is a first documentation where
      exclusively nuclear and non-nuclear domains have been identified and used for
      predicting nuclear proteins. The performance of the method improved further by
      combining both approaches together.

PMID- 19152694
TI  - The function of APC/CCdh1 in cell cycle and beyond.
AB  - The anaphase promoting complex/cyclosome (APC/C) is a multi-subunit E3 ubiquitin
      ligase playing essential functions in mitosis. It is conserved from yeast to
      human and relies on two adaptor proteins, Cdc20 and Cdh1, to bring in substrates.
      Both APCCdc20 and APCCdh1 are implicated in the control of mitosis through
      mediating ubiquitination and degradation of important mitotic regulators such as
      cyclin B1, securin, and Plk1. In addition, APCCdh1 is thought to prevent
      premature S phase entry by limiting the accumulation of mitotic cyclins in G1 and
      to regulate processes unrelated to cell cycle. In this review, we will summarize
      our current understanding of APCCdh1 function in cell cycle and beyond.

PMID- 19152695
TI  - Feasibility of laparoscopy for small bowel obstruction.
AB  - BACKGROUND: Adherential pathology is the most common cause of small bowel
      obstruction. Laparoscopy in small bowel obstruction does not have a clear role
      yet; surely it doesn't always represent only a therapeutic act, but it is always
      a diagnostic act, which doesn't interfere with abdominal wall integrity. METHODS:
      We performed a review without any language restrictions considering international
      literature indexed from 1980 to 2007 in Medline, Embase and Cochrane Library. We
      analyzed the reference lists of the key manuscripts. We also added a review based
      on international non-indexed sources. RESULTS: The feasibility of diagnostic
      laparoscopy is high (60-100%), while that of therapeutic laparoscopy is low (40
      88%). The frequency of laparotomic conversions is variable ranging from 0 to 52%,
      depending on patient selection and surgical skill. The first cause of laparotomic
      conversion is a difficult exposition and treatment of band adhesions. The
      incidence of laparotomic conversions is major in patients with anterior
      peritoneal band adhesions. Other main causes for laparotomic conversion are the
      presence of bowel necrosis and accidental enterotomies. The predictive factors
      for successful laparoscopic adhesiolysis are: number of previous laparotomies </=
      2, non-median previous laparotomy, appendectomy as previous surgical treatment
      causing adherences, unique band adhesion as phatogenetic mechanism of small bowel
      obstruction, early laparoscopic management within 24 hours from the onset of
      symptoms, no signs of peritonitis on physical examination, experience of the
      surgeon. CONCLUSION: Laparoscopic adhesiolysis in small bowel obstruction is
      feasible but can be convenient only if performed by skilled surgeons in selected
      patients. The laparoscopic adhesiolysis for small bowel obstruction is
      satisfactorily carried out when early indicated in patients with a low number of
      laparotomies resulting in a short hospital stay and a lower postoperative
      morbidity. Although a higher small bowel obstruction recurrence remains the major
      postoperative risk of the laparoscopic management of these patients.

PMID- 19152696
TI  - Effect of false positive and false negative rates on inference of binding target
      conservation across different conditions and species from ChIP-chip data.
AB  - BACKGROUND: ChIP-chip data are routinely used to identify transcription factor
      binding targets. However, the presence of false positives and false negatives in
      ChIP-chip data complicates and hinders analyses, especially when the binding
      targets for a specific transcription factor are compared across conditions or
      species. RESULTS: We propose an Expectation Maximization based approach to infer
      the underlying true counts of "positives" and "negatives" from the observed
      counts. Based on this approach, we study the effect of false positives and false
      negatives on inferences related to transcription regulation. CONCLUSION: Our
      results indicate that if there is a significant degree of association among the
      binding targets across conditions/species (log odds ratio > 4), moderate values
      of false positive and false negative rates (0.005 and 0.4 respectively) would not
      change our inference qualitatively (i.e. the presence or absence of conservation)
      based on the observed experimental data despite a significant change in the
      observed counts. However, if the underlying association is marginal, with odds
      ratios close to 1, moderate to large values of false positive and false negative
      rates (0.01 and 0.2 respectively) could mask the underlying association.

PMID- 19152697
TI  - Incidence and trends of low back pain hospitalisation during military service--an
      analysis of 387,070 Finnish young males.
AB  - BACKGROUND: There is evidence that low back pain (LBP) during young adulthood and
      military service predicts LBP later in life. The purpose of this study was to
      investigate the incidence and trends of LBP hospitalisation among Finnish
      military conscripts. METHODS: All male conscripts performing their compulsory
      military service during 1990-2002 were included in the study population.
      Altogether 387,070 military conscripts were followed throughout their six-to
      twelve-month service period. Data on LBP hospitalisations were obtained from the
      National Hospital Discharge Register. RESULTS: Altogether 7,240 LBP
      hospitalisations were identified among 5,061 (1.3%) male conscripts during the
      study period. The event-based incidence of LBP hospitalisation was 27.0 (95%
      confidence interval (CI): 25.7-28.2). In most cases, the diagnosis was
      unspecified LBP (n = 5,141, 71%) followed by lumbar disc disorders (n = 2,069,
      29%). Hospitalisation incidence due to unspecified LBP was 19.1 per 1,000 person
      years (95% CI: 18.3 to 20.4), and 7.8 per 1,000 person-years (95% CI: 6.7 to 8.3)
      due to lumbar disc disorders. The incidence of unspecified LBP remained
      unaltered, while hospitalisation due to lumbar disc disorders declined from 1993
      onwards. CONCLUSION: Although conscripts accepted into military training pass
      physician-performed examinations as healthy, young adults, LBP hospitalisation
      causes significant morbidity during military service.

PMID- 19152698
TI  - Clinical predictors for Legionella in patients presenting with community-acquired
      pneumonia to the emergency department.
AB  - BACKGROUND: Legionella species cause severe forms of pneumonia with high
      mortality and complication rates. Accurate clinical predictors to assess the
      likelihood of Legionella community-acquired pneumonia (CAP) in patients
      presenting to the emergency department are lacking. METHODS: We retrospectively
      compared clinical and laboratory data of 82 consecutive patients with Legionella
      CAP with 368 consecutive patients with non-Legionella CAP included in two studies
      at the same institution. RESULTS: In multivariate logistic regression analysis we
      identified six parameters, namely high body temperature (OR 1.67, p < 0.0001),
      absence of sputum production (OR 3.67, p < 0.0001), low serum sodium
      concentrations (OR 0.89, p = 0.011), high levels of lactate dehydrogenase (OR
      1.003, p = 0.007) and C-reactive protein (OR 1.006, p < 0.0001) and low platelet
      counts (OR 0.991, p < 0.0001), as independent predictors of Legionella CAP. Using
      optimal cut off values of these six parameters, we calculated a diagnostic score
      for Legionella CAP. The median score was significantly higher in Legionella CAP
      as compared to patients without Legionella (4 (IQR 3-4) vs 2 (IQR 1-2), p <
      0.0001) with a respective odds ratio of 3.34 (95%CI 2.57-4.33, p < 0.0001).
      Receiver operating characteristics showed a high diagnostic accuracy of this
      diagnostic score (AUC 0.86 (95%CI 0.81-0.90), which was better as compared to
      each parameter alone. Of the 191 patients (42%) with a score of 0 or 1 point,
      only 3% had Legionella pneumonia. Conversely, of the 73 patients (16%) with > or
      =4 points, 66% of patients had Legionella CAP. CONCLUSION: Six clinical and
      laboratory parameters embedded in a simple diagnostic score accurately identified
      patients with Legionella CAP. If validated in future studies, this score might
      aid in the management of suspected Legionella CAP.

PMID- 19152699
TI  - Quality assessment of diagnostic before-after studies: development of methodology
      in the context of a systematic review.
AB  - BACKGROUND: Quality assessment tools for primary studies of test accuracy are
      relatively well developed, although only one is validated (QUADAS), but very
      little work has been done to develop tools to quality-assess studies evaluating
      the impact of diagnostic testing on management of patients (diagnostic or
      therapeutic yield). The recent draft NICE Guide to the Methods of Technology
      Appraisal (2007) suggests QUADAS "as a useful starting point for appraising
      studies that evaluate the sensitivity and specificity of a test" but does not
      mention how to quality assess diagnostic or therapeutic yield studies, in
      particular diagnostic before-after studies. In the context of undertaking a rapid
      systematic review of structural neuroimaging in psychosis for NICE, we describe
      the modifications that we made to QUADAS, our experience of this in practice and
      in relation to published theory on diagnostic or therapeutic yield studies.
      METHODS: The QUADAS tool was assessed for use in the review by two systematic
      reviewers with in-depth knowledge of the clinical area being reviewed and the
      types of studies being found in the searches that could answer the clinical
      question. Modifications were made following discussion as considered appropriate.
      RESULTS: Two QUADAS questions were removed altogether and. four additional
      questions were developed to capture additional quality issues not addressed by
      QUADAS. However, the developed checklist only partially helped to discern
      implications of the study designs on the results given. CONCLUSION: The division
      between topic-specific and more generic quality items of relevance to diagnostic
      before-after studies is important. With more time, further work could have been
      done to create a better quality assessment tool, for example by incorporating
      some of the issues mentioned in previous work in this area. This paper is a
      discussion around quality assessment and is intended to offer insights into the
      types of issues that should be assessed. A quality assessment tool for diagnostic
      before-after studies that incorporates items from QUADAS and published theory
      needs to be further developed and validated.

PMID- 19152700
TI  - Quality of life in chemical warfare survivors with ophthalmologic injuries: the
      first results form Iran Chemical Warfare Victims Health Assessment Study.
AB  - BACKGROUND: Iraq used chemical weapons extensively against the Iranians during
      the Iran-Iraq war (1980-1988). The aim of this study was to assess the health
      related quality of life (HRQOL) in people who had ophthalmologic complications
      due to the sulfur mustard gas exposure during the war. METHODS: The Veterans and
      Martyrs Affair Foundation (VMAF) database indicated that there were 196 patients
      with severe ophthalmologic complications due to chemical weapons exposure. Of
      these, those who gave consent (n = 147) entered into the study. Quality of life
      was measured using the 36-item Short Form Health Survey (SF-36) and scores were
      compared to those of the general public. In addition logistic regression analysis
      was performed to indicate variables that contribute to physical and mental health
      related quality of life. RESULTS: The mean age of the patients was 44.8 (SD =
      8.7) ranging from 21 to 75 years. About one-third of the cases (n= 50) reported
      exposure to chemical weapons more than once. The mean exposure duration to sulfur
      mustard gas was 21.6 years (SD = 1.2). The lowest scores on the SF-36 subscales
      were found to be: the role physical and the general health. Quality of life in
      chemical warfare victims who had ophthalmologic problems was significantly lower
      than the general public (P < 0.001). The results obtained from logistic
      regression analysis indicated that those who did not participate in sport
      activities suffer from a poorer physical health (OR = 2.93, 95% CI = 1.36 to
      6.30, P = 0.006). The analysis also showed that poor mental health was associated
      with longer time since exposure (OR = 1.58, 95% CI = 1.04 to 2.39, P = 0.03) and
      lower education (OR = 3.03, 95% CI = 1.21 to 7.56, P = 0.01). CONCLUSION: The
      study findings suggest that chemical warfare victims with ophthalmologic
      complications suffer from poor health related quality of life. It seems that the
      need for provision of health and support for this population is urgent. In
      addition, further research is necessary to measure health related quality of life
      in victims with different types of disabilities in order to support and enhance
      quality of life among this population.

PMID- 19152701
TI  - Silica-based cationic bilayers as immunoadjuvants.
AB  - BACKGROUND: Silica particles cationized by dioctadecyldimethylammonium bromide
      (DODAB) bilayer were previously described. This work shows the efficiency of
      these particulates for antigen adsorption and presentation to the immune system
      and proves the concept that silica-based cationic bilayers exhibit better
      performance than alum regarding colloid stability and cellular immune responses
      for vaccine design. RESULTS: Firstly, the silica/DODAB assembly was characterized
      at 1 mM NaCl, pH 6.3 or 5 mM Tris.HCl, pH 7.4 and 0.1 mg/ml silica over a range
      of DODAB concentrations (0.001-1 mM) by means of dynamic light scattering for
      particle sizing and zeta-potential analysis. 0.05 mM DODAB is enough to produce
      cationic bilayer-covered particles with good colloid stability. Secondly,
      conditions for maximal adsorption of bovine serum albumin (BSA) or a recombinant,
      heat-shock protein from Mycobacterium leprae (18 kDa-hsp) onto DODAB-covered or
      onto bare silica were determined. At maximal antigen adsorption, cellular immune
      responses in vivo from delayed-type hypersensitivity reactions determined by foot
      pad swelling tests (DTH) and cytokines analysis evidenced the superior
      performance of the silica/DODAB adjuvant as compared to alum or antigens alone
      whereas humoral response from IgG in serum was equal to the one elicited by alum
      as adjuvant. CONCLUSION: Cationized silica is a biocompatible, inexpensive,
      easily prepared and possibly general immunoadjuvant for antigen presentation
      which displays higher colloid stability than alum, better performance regarding
      cellular immune responses and employs very low, micromolar doses of cationic and
      toxic synthetic lipid.

PMID- 19152702
TI  - Sexual behavior and drug consumption among young adults in a shantytown in Lima,
      Peru.
AB  - BACKGROUND: Risky sexual behaviors of young adults have received increasing
      attention during the last decades. However, few studies have focused on the
      sexual behavior of young adults in shantytowns of Latin America. Specifically,
      studies on the association between sexual behaviors and other risk factors for
      sexually transmitted infections (STI) and HIV/AIDS transmission, such as the
      consumption of illicit drugs or alcohol are scarce in this specific context.
      METHODS: The study participants were 393 men and 400 women between 18 and 30
      years of age, from a shantytown in Lima, Peru. Data were obtained via survey: one
      section applied by a trained research assistant, and a self-reporting section.
      Logistic regression was used to estimate associations between use of any illicit
      drug, high-risk sexual behaviors and reported STI symptoms, adjusting for alcohol
      consumption level and various socio-demographic characteristics. RESULTS: Among
      men, age of sexual debut was lower, number of lifetime sexual partners was
      higher, and there were higher risk types of sexual partners, compared to women.
      Though consistent condom use with casual partners was low in both groups,
      reported condom use at last intercourse was higher among men than women. Also, a
      lifetime history of illicit drug consumption decreased the probability of condom
      use at last sexual intercourse by half. Among men, the use of illicit drugs
      doubled the probability of intercourse with a casual partner during the last year
      and tripled the probability of reported STI symptoms. CONCLUSION: Drug
      consumption is associated with high-risk sexual behaviors and reported STI
      symptoms in a Lima shantytown after controlling for alcohol consumption level.
      Development of prevention programs for risky sexual behaviors, considering gender
      differences, is discussed.

PMID- 19152703
TI  - Nitric oxide gas phase release in human small airway epithelial cells.
AB  - BACKGROUND: Asthma is a chronic airway inflammatory disease characterized by an
      imbalance in both Th1 and Th2 cytokines. Exhaled nitric oxide (NO) is elevated in
      asthma, and is a potentially useful non-invasive marker of airway inflammation.
      However, the origin and underlying mechanisms of intersubject variability of
      exhaled NO are not yet fully understood. We have previously described NO gas
      phase release from normal human bronchial epithelial cells (NHBEs, tracheal
      origin). However, smaller airways are the major site of morbidity in asthma. We
      hypothesized that IL-13 or cytomix (IL-1beta, TNF-alpha, and IFN-gamma)
      stimulation of differentiated small airway epithelial cells (SAECs, generation 10
      12) and A549 cells (model cell line of alveolar type II cells) in culture would
      enhance NO gas phase release. METHODS: Confluent monolayers of SAECs and A549
      cells were cultured in Transwell plates and SAECs were allowed to differentiate
      into ciliated and mucus producing cells at an air-liquid interface. The cells
      were then stimulated with IL-13 (10 ng/mL) or cytomix (10 ng/mL for each
      cytokine). Gas phase NO release in the headspace air over the cells was measured
      for 48 hours using a chemiluminescence analyzer. RESULTS: In contrast to our
      previous result in NHBE, baseline NO release from SAECs and A549 is negligible.
      However, NO release is significantly increased by cytomix (0.51 +/- 0.18 and 0.29
      +/- 0.20 pl.s-1.cm-2, respectively) reaching a peak at approximately 10 hours.
      iNOS protein expression increases in a consistent pattern both temporally and in
      magnitude. In contrast, IL-13 only modestly increases NO release in SAECs
      reaching a peak (0.06 +/- 0.03 pl.s-1.cm-2) more slowly (30 to 48 hours), and
      does not alter NO release in A549 cells. CONCLUSION: We conclude that the airway
      epithelium is a probable source of NO in the exhaled breath, and intersubject
      variability may be due, in part, to variability in the type (Th1 vs Th2) and
      location (large vs small airway) of inflammation.

PMID- 19152704
TI  - Mechanical ventilation using non-injurious ventilation settings causes lung
      injury in the absence of pre-existing lung injury in healthy mice.
AB  - INTRODUCTION: Mechanical ventilation (MV) may cause ventilator-induced lung
      injury (VILI). Present models of VILI use exceptionally large tidal volumes,
      causing gross lung injury and haemodynamic shock. In addition, animals are
      ventilated for a relative short period of time and only after a 'priming'
      pulmonary insult. Finally, it is uncertain whether metabolic acidosis, which
      frequently develops in models of VILI, should be prevented. To study VILI in
      healthy mice, the authors used a MV model with clinically relevant ventilator
      settings, avoiding massive damage of lung structures and shock, and preventing
      metabolic acidosis. METHODS: Healthy C57Bl/6 mice (n = 66) or BALB/c mice (n =
      66) were ventilated (tidal volume = 7.5 ml/kg or 15 ml/kg; positive end
      expiratory pressure = 2 cmH2O; fraction of inspired oxygen = 0.5) for five hours.
      Normal saline or sodium bicarbonate were used to correct for hypovolaemia. Lung
      histopathology, lung wet-to-dry ratio, bronchoalveolar lavage fluid protein
      content, neutrophil influx and levels of proinflammatory cytokines and
      coagulation factors were measured. RESULTS: Animals remained haemodynamically
      stable throughout the whole experiment. Lung histopathological changes were
      minor, although significantly more histopathological changes were found after
      five hours of MV with a larger tidal volume. Lung histopathological changes were
      no different between the strains. In both strains and with both ventilator
      settings, MV caused higher wet-to-dry ratios, higher bronchoalveolar lavage fluid
      protein levels and more influx of neutrophils, and higher levels of
      proinflammatory cytokines and coagulation factors. Also, with MV higher systemic
      levels of cytokines were measured. All parameters were higher with larger tidal
      volumes. Correcting for metabolic acidosis did not alter endpoints. CONCLUSIONS:
      MV induces VILI, in the absence of a priming pulmonary insult and even with use
      of relevant (least injurious) ventilator settings. This model offers
      opportunities to study the pathophysiological mechanisms behind VILI and the
      contribution of MV to lung injury in the absence of pre-existing lung injury.

PMID- 19152705
TI  - An innovative approach for testing bioinformatics programs using metamorphic
      testing.
AB  - BACKGROUND: Recent advances in experimental and computational technologies have
      fueled the development of many sophisticated bioinformatics programs. The
      correctness of such programs is crucial as incorrectly computed results may lead
      to wrong biological conclusion or misguided downstream experimentation. Common
      software testing procedures involve executing the target program with a set of
      test inputs and then verifying the correctness of the test outputs. However, due
      to the complexity of many bioinformatics programs, it is often difficult to
      verify the correctness of the test outputs. Therefore our ability to perform
      systematic software testing is greatly hindered. RESULTS: We propose to use a
      novel software testing technique, metamorphic testing (MT), to test a range of
      bioinformatics programs. Instead of requiring a mechanism to verify whether an
      individual test output is correct, the MT technique verifies whether a pair of
      test outputs conform to a set of domain specific properties, called metamorphic
      relations (MRs), thus greatly increases the number and variety of test cases that
      can be applied. To demonstrate how MT is used in practice, we applied MT to test
      two open-source bioinformatics programs, namely GNLab and SeqMap. In particular
      we show that MT is simple to implement, and is effective in detecting faults in a
      real-life program and some artificially fault-seeded programs. Further, we
      discuss how MT can be applied to test programs from various domains of
      bioinformatics. CONCLUSION: This paper describes the application of a simple,
      effective and automated technique to systematically test a range of
      bioinformatics programs. We show how MT can be implemented in practice through
      two real-life case studies. Since many bioinformatics programs, particularly
      those for large scale simulation and data analysis, are hard to test
      systematically, their developers may benefit from using MT as part of the testing
      strategy. Therefore our work represents a significant step towards software
      reliability in bioinformatics.

PMID- 19152706
TI  - Acute abdomen caused by ingested chicken wishbone: a case report.
AB  - INTRODUCTION: An ingested foreign body often passes the gastrointestinal tract
      without any complications. Foreign bodies, such as dentures, fish bones, chicken
      bones, and toothpicks, have been known to cause perforation of the GI tract. CASE
      PRESENTATION: We are presenting a case of a fifty-year-old male with acute
      abdomen; diffuse fibro purulent peritonitis, i.e. ileum perforation, caused by
      accidentally ingesting a chicken wishbone. He was treated surgically with ileum
      resection, and temporary ileostomy. After four months, intestinal continuity was
      established in the second operation. CONCLUSION: Intestinal perforation by a
      chicken bone is rare and affects the left colon or distal ileum. The lack of
      information of ingestion and detection of chicken bones preoperatively are of
      interest to be considered in the differential diagnosis of acute abdomen, which
      in this case was treated surgically.

PMID- 19152707
TI  - Malaria transmission in two localities in north-western Argentina.
AB  - BACKGROUND: Malaria is one of the most important tropical diseases that affects
      people globally. The influence of environmental conditions in the patterns of
      temporal distribution of malaria vectors and the disease has been studied in
      different countries. In the present study, ecological aspects of the malaria
      vector Anopheles (Anopheles) pseudopunctipennis and their relationship with
      climatic variables, as well as the seasonality of malaria cases, were studied in
      two localities, El Oculto and Aguas Blancas, in north-western Argentina. METHODS:
      The fluctuation of An. pseudopunctipennis and the malaria cases distribution was
      analysed with Random Effect Poisson Regression. This analysis takes into account
      the effect of each climatic variable on the abundance of both vector and malaria
      cases, giving as results predicted values named Incidence Rate Radio. RESULTS:
      The number of specimens collected in El Oculto and Aguas Blancas was 4224
      (88.07%) and 572 (11.93%), respectively. In El Oculto no marked seasonality was
      found, different from Aguas Blancas, where high abundance was detected at the end
      of spring and the beginning of summer. The maximum mean temperature affected the
      An. pseudopunctipennis fluctuation in El Oculto and Aguas Blancas. When
      considering the relationship between the number of malaria cases and the climatic
      variables in El Oculto, maximum mean temperature and accumulated rainfall were
      significant, in contrast with Aguas Blancas, where mean temperature and humidity
      showed a closer relationship to the fluctuation in the disease. CONCLUSION: The
      temporal distribution patterns of An. pseudopunctipennis vary in both localities,
      but spring appears as the season with better conditions for mosquito development.
      Maximum mean temperature was the most important variable in both localities.
      Malaria cases were influenced by the maximum mean temperature in El Oculto, while
      the mean temperature and humidity were significant in Aguas Blancas. In Aguas
      Blancas peaks of mosquito abundance and three months later, peaks of malaria
      cases were observed. The study reported here will help to increase knowledge
      about not only vectors and malaria seasonality but also their relationships with
      the climatic variables that influence their appearances and abundances.

PMID- 19152708
TI  - Tobacco farming in rural Vietnam: questionable economic gain but evident health
      risks.
AB  - BACKGROUND: In order to provide evidence on health impacts of the tobacco
      industry on cultivators in Vietnam, this study aims to provide comparison between
      tobacco cultivation related revenue and expenditure in selected areas in rural
      Vietnam and examine the relationship between tobacco cultivation and self
      reported illness in the study population. METHODS: Two tobacco farming communes
      and two non-tobacco farming communes were selected for this study. In each
      selected commune, 120 households were sampled using two-stage cluster sampling
      technique. Local health workers were recruited and trained to conduct household
      interviews using structured questionnaire. RESULTS: Where the expenditure figures
      do not include personnel costs (as the farming work was almost always responsible
      by the family members themselves), it appeared that the average tobacco farmer
      did benefit financially from tobacco cultivation. However, if a personal
      opportunity cost was added to give a financial value to their labour, the profit
      from tobacco cultivation was seen to be minimal. The occurrences of 9 out of the
      16 health problems were statistically significant higher among tobacco growing
      farmers compared to that among non-tobacco farmers. Tobacco farming was shown to
      be the second strong predictor of self-reported health problems among the farmer
      (after the effect of old age). CONCLUSION: The present study provides evidence
      that can be used to increase public awareness about the harmful effects of
      tobacco growing.

PMID- 19152709
TI  - Quantifying the profile and progression of impairments, activity, participation,
      and quality of life in people with Parkinson disease: protocol for a prospective
      cohort study.
AB  - BACKGROUND: Despite the finding that Parkinson disease (PD) occurs in more than
      one in every 1000 people older than 60 years, there have been few attempts to
      quantify how deficits in impairments, activity, participation, and quality of
      life progress in this debilitating condition. It is unclear which tools are most
      appropriate for measuring change over time in PD. METHODS AND DESIGN: This
      protocol describes a prospective analysis of changes in impairments, activity,
      participation, and quality of life over a 12 month period together with an
      economic analysis of costs associated with PD. One-hundred participants will be
      included, provided they have idiopathic PD rated I-IV on the modified Hoehn &
      Yahr (1967) scale and fulfil the inclusion criteria. The study aims to determine
      which clinical and economic measures best quantify the natural history and
      progression of PD in a sample of people receiving services from the Victorian
      Comprehensive Parkinson's Program, Australia. When the data become available, the
      results will be expressed as baseline scores and changes over 3 months and 12
      months for impairment, activity, participation, and quality of life together with
      a cost analysis. DISCUSSION: This study has the potential to identify baseline
      characteristics of PD for different Hoehn & Yahr stages, to determine the
      influence of disease duration on performance, and to calculate the costs
      associated with idiopathic PD. Valid clinical and economic measures for
      quantifying the natural history and progression of PD will also be identified.
      TRIAL REGISTRATION: ACTRN12609000008224.

PMID- 19152710
TI  - TRIP-Br2 promotes oncogenesis in nude mice and is frequently overexpressed in
      multiple human tumors.
AB  - BACKGROUND: Members of the TRIP-Br/SERTAD family of mammalian transcriptional
      coregulators have recently been implicated in E2F-mediated cell cycle progression
      and tumorigenesis. We, herein, focus on the detailed functional characterization
      of the least understood member of the TRIP-Br/SERTAD protein family, TRIP-Br2
      (SERTAD2). METHODS: Oncogenic potential of TRIP-Br2 was demonstrated by (1)
      inoculation of NIH3T3 fibroblasts, which were engineered to stably overexpress
      ectopic TRIP-Br2, into athymic nude mice for tumor induction and (2)
      comprehensive immunohistochemical high-throughput screening of TRIP-Br2 protein
      expression in multiple human tumor cell lines and human tumor tissue microarrays
      (TMAs). Clinicopathologic analysis was conducted to assess the potential of TRIP
      Br2 as a novel prognostic marker of human cancer. RNA interference of TRIP-Br2
      expression in HCT-116 colorectal carcinoma cells was performed to determine the
      potential of TRIP-Br2 as a novel chemotherapeutic drug target. RESULTS:
      Overexpression of TRIP-Br2 is sufficient to transform murine fibroblasts and
      promotes tumorigenesis in nude mice. The transformed phenotype is characterized
      by deregulation of the E2F/DP-transcriptional pathway through upregulation of the
      key E2F-responsive genes CYCLIN E, CYCLIN A2, CDC6 and DHFR. TRIP-Br2 is
      frequently overexpressed in both cancer cell lines and multiple human tumors.
      Clinicopathologic correlation indicates that overexpression of TRIP-Br2 in
      hepatocellular carcinoma is associated with a worse clinical outcome by Kaplan
      Meier survival analysis. Small interfering RNA-mediated (siRNA) knockdown of TRIP
      Br2 was sufficient to inhibit cell-autonomous growth of HCT-116 cells in vitro.
      CONCLUSION: This study identifies TRIP-Br2 as a bona-fide protooncogene and
      supports the potential for TRIP-Br2 as a novel prognostic marker and a
      chemotherapeutic drug target in human cancer.

PMID- 19152711
TI  - A study of best positive predictors for sustained virologic response to
      interferon alpha plus ribavirin therapy in naive chronic hepatitis C patients.
AB  - BACKGROUND: The aim of this study was to determine the rate of sustained
      virological response (SVR) and various factors associated with response rates in
      chronic hepatitis C infected patients treated with interferon alpha and ribavirin
      combination therapy. METHODS: A retrospective review of patients data collected
      at this Centre from 2001 to 2007 was performed. Out of 731 consecutive patients
      400 patients that fulfilled the study criteria were evaluated and subsequently
      treated with a combination of interferon alpha 2b (3 MU subcutaneously three
      injections weekly) and ribavirin (800-1200 mg orally daily). Treatment were
      administered for either 24 weeks or 48 weeks and patients were followed for an
      additional 6 months thereafter. End of the treatment response (ETR), SVR and side
      effects were recorded. RESULTS: Out of 400 patients, 394 completed the entire
      treatment course and six patients discontinued treatment at month 2. Over 67%
      responded at the end of treatment and 16% suffered relapse. Among all treated
      patients, 47.6% males and 56.7% females had sustained viral response with a total
      combined sustained viral response rate of 50.5%. Rapid response was seen in 46.5%
      patients. In a multivariate logistic regression analysis, slow virological
      responders (adjusted OR 2.6 [95% CI 1.9-3.7]), HCV genotype 1&4 (adjusted OR 2.4
      [95% CI 1.7-3.5]), pre-treatment viral load > 0.2 MIU/mL (adjusted OR 2.2 [95% CI
      1.8-4.2]), Panjabi ethnic group (adjusted OR 1.6 [95% CI 1.0-3.2]) and Age > 40
      years (adjusted OR 1.5 [95% CI 0.9-2.4]) were independent risk factors for non
      response. Side effects were usual and tolerable and only 1.5% discontinued the
      treatment. CONCLUSION: The best positive predictor for SVR in this country are:
      rapid virologic response, HCV genotype 2 & 3, age < 40 years, ethnic race
      Pashtoons and pre-treatment viral load < 0.2 million IU/mL.

PMID- 19152712
TI  - Extramedullary myeloma in an HIV-seropositive subject. Literature review and
      report of an unusual case.
AB  - Myeloma is characterized by monoclonal bone marrow plasmacytosis, the presence of
      M-protein in serum and/or in urine and osteolytic bone lesions. HIV-seropositive
      subjects with myeloma are younger at the time of diagnosis of the tumour and
      usually the myeloma has a more aggressive clinical course than it does in HIV
      seronegative subjects. A case of an HIV-seropositive woman in whom myeloma was
      diagnosed following progressive swelling of the face, is reported. In addition to
      bone marrow plasmacytosis and the presence of M-protein in the serum, the patient
      had an extramedullary lesion affecting the oral cavity, maxilla, parotid gland
      and paranasal sinuses, and extending intracranially and intraorbitally.

PMID- 19152713
TI  - Livestock grazing intensity affects abundance of Common shrews (Sorex araneus) in
      two meadows in Denmark.
AB  - BACKGROUND: Current nature conservation in semi-natural grasslands often includes
      grazing and hay cutting, as well as the abandonment of draining. Semi-natural
      grassland and in particular meadows constitute important habitat type for a large
      number of animal species in today's fragmented and intensively cultivated
      landscape of Europe. Here we focus on the population characteristics of Common
      shrews Sorex araneus in relation to livestock grazing intensity in two wet
      meadows in western Denmark. RESULTS: High grazing intensity had a significant
      negative effect on Common shrew number compared to low grazing intensity and no
      grazing. Common shrew abundance was generally, but not significantly, higher on
      the low grazing intensity plots than on the ungrazed controls. No differences in
      body mass, sex ratio, or reproductive output between Common shrew individuals
      from the various grazing treatments were found. CONCLUSION: No negative effects
      of low intensity grazing on Common shrew abundance were found compared to the
      ungrazed control. Low intensity grazing thus seems a suitable management regime
      for Common shrews, when grazing is needed as part of the meadow management
      scheme. High intensity grazing on the other hand is not a suitable management
      tool.

PMID- 19152714
TI  - 5th international conference on conservative management of spinal deformities
      athens, Greece. 3-5 april 2008. Abstracts.

PMID- 19152715
TI  - Forage to concentrate ratio in Jonica breed goats: influence on lactation curve
      and milk composition.
AB  - The aim of the work is to evaluate the effects of different forage to concentrate
      rations on milk yield, composition and renneting properties of milk of Jonica
      breed goats. Twenty-four Jonica goats received diets with forage to concentrate
      ratio of 35/65, 50/50 or 65/35, providing respectively a low, medium and high
      energy level. Goats were divided into three homogenous groups and confined in
      individual pens for 152 days to assess the daily feed intake and milk yield and
      composition. The main conclusions show that animal body weight did not change
      significantly with the increasing levels of forage, whereas significant
      differences (P<0.05) for daily dry matter intake were observed in relation to the
      evolution of lactation. Milk production was influenced (P<0.05) by dietary
      treatments and was higher in the diet with the greatest energy level. Forage to
      concentrate ratios did not significantly affect milk characteristics, milk
      renneting properties, initial production, rate of increase until reaching the
      peak and rate of decline after peak production. However, the day of peak
      production and peak production of goats were linearly reduced when the level of
      forage increased within the diet. In conclusion, the results indicate that both
      forage to concentrate ratio and energy level improve goat's production without
      influencing the milk composition.

PMID- 19152716
TI  - Iodine nutritional status of children on the island of Tanna, Republic of
      Vanuatu.
AB  - OBJECTIVE: To evaluate the iodine nutritional status of children living on the
      island of Tanna, Republic of Vanuatu. DESIGN: Cross-sectional study. Urine and
      household salt samples were collected for iodine measurement. Thyroid volumes
      were measured by ultrasound. A food consumption frequency survey was carried out,
      particularly in relation to salt, iodine-rich foods and foods that containing
      thiocyanate, a potentially goitrogenic substance. Urinary thiocyanate levels were
      also measured. SETTING: Island rural communities in Tanna, Vanuatu. SUBJECTS: One
      hundred and fifty-three schoolchildren between 8 and 10 years of age from four
      locations on the island participated. RESULTS: The median urinary iodine
      excretion (UIE) among the children was 49 mg/l, indicating moderate iodine
      deficiency. This was corroborated by 27% of boys and 33% of girls having thyroid
      glands greater than the international standard for their age, and 36% of boys and
      45% of girls having thyroid glands greater than the international standard for
      their body surface area based on ultrasonography. There was a highly
      statistically significant inverse correlation between thyroid volume and UIE for
      boys and girls (r = -0.444, P = 0.001 and r = -0.319, P = 0.005, respectively).
      There was no correlation between thiocyanate and UIE or thyroid volume. Only 34%
      of children reported to consume fish (tinned or fresh) on a weekly basis.
      CONCLUSIONS: Against the common perception, the study has demonstrated that the
      children on the island of Tanna were in a state of moderate iodine deficiency.
      More data need to be collected from other Pacific Island countries in order to
      provide evidence for formulating public policy in prevention and control of
      iodine deficiency disorders in these nations.

PMID- 19152717
TI  - Independence of color and luminance edges in natural scenes.
AB  - Form vision is traditionally regarded as processing primarily achromatic
      information. Previous investigations into the statistics of color and luminance
      in natural scenes have claimed that luminance and chromatic edges are not
      independent of each other and that any chromatic edge most likely occurs together
      with a luminance edge of similar strength. Here we computed the joint statistics
      of luminance and chromatic edges in over 700 calibrated color images from natural
      scenes. We found that isoluminant edges exist in natural scenes and were not
      rarer than pure luminance edges. Most edges combined luminance and chromatic
      information but to varying degrees such that luminance and chromatic edges were
      statistically independent of each other. Independence increased along successive
      stages of visual processing from cones via postreceptoral color-opponent channels
      to edges. The results show that chromatic edge contrast is an independent source
      of information that can be linearly combined with other cues for the proper
      segmentation of objects in natural and artificial vision systems. Color vision
      may have evolved in response to the natural scene statistics to gain access to
      this independent information.

PMID- 19152718
TI  - The role of binocular vision in walking.
AB  - Despite the extensive investigation of binocular and stereoscopic vision,
      relatively little is known about its importance in natural visually guided
      behavior. In this paper, we explored the role of binocular vision when walking
      over and around obstacles. We monitored eye position during the task as an
      indicator of the difference between monocular and binocular performances. We
      found that binocular vision clearly facilitates walking performance. Walkers were
      slowed by about 10% in monocular vision and raised their foot higher when
      stepping over obstacles. Although the location and sequence of the fixations did
      not change in monocular vision, the timing of the fixations relative to the
      actions was different. Subjects spent proportionately more time fixating the
      obstacles and fixated longer while guiding foot placement near an obstacle. The
      data are consistent with greater uncertainty in monocular vision, leading to a
      greater reliance on feedback in the control of the movements.

PMID- 19152720
TI  - Frontal recess cells: a rare cause of frontal sinus pneumocoele.
AB  - BACKGROUND AND AIMS: A pneumocoele is a pathologically expanding, air-containing
      paranasal sinus. Pneumocoeles are uncommon entities, with very few cases reported
      in the literature. The most plausible aetiological theory is that of a one-way
      valve effect allowing air into the sinus under increased pressure without
      pressure equilibration. METHODS: Review of a frontal sinus pneumocoele caused by
      a type III frontal cell and intersinus septal cell. RESULTS: We present a patient
      with chronic sinusitis who developed a pneumocoele of her left frontal sinus with
      erosion into her orbit. This patient was a habitual, chronic nose-blower with a
      large type III frontal cell adjacent to an intersinus septal cell. CONCLUSION: We
      propose the new theory that, in our patient, such cells formed a one-way valve,
      causing air-trapping and pathological expansion of the frontal sinus. To our
      knowledge, there are no previously published cases that establish an association
      between large frontal cells and expansion of a pneumocoele.

PMID- 19152721
TI  - Parotid dermoid cyst: a rare entity.
AB  - OBJECTIVE: We report a rare case of parotid dermoid cyst. METHOD: A case report
      of parotid dermoid cyst is presented, as well as a brief review of the literature
      and a summary of the lesion's salient clinicopathological features. RESULTS: A 69
      year-old man presented with a slow-growing, soft tissue mass of the left parotid
      gland. Pre-operative evaluation included fine needle aspiration cytology and
      computed tomography. He subsequently underwent a superficial lobectomy; both the
      macroscopic and histopathological findings were consistent with a dermoid cyst.
      Although dermoids within the head and neck are not uncommon, such cysts have only
      rarely been encountered in the parotid gland. CONCLUSION: To our knowledge, there
      are only four previous case reports of parotid dermoid cyst in the English
      literature. Although the majority of cases of parotid dermoid cyst are diagnosed
      retrospectively, our case demonstrates the role of fine needle aspiration
      cytology and highlights the key cytological features suggestive of this entity.

PMID- 19152719
TI  - Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic
      prospects for neuroinflammation.
AB  - There is now a large body of data indicating that the cannabinoid receptor type 2
      (CB2) is linked to a variety of immune events. This functional relevance appears
      to be most salient in the course of inflammation, a process during which there is
      an increased number of receptors that are available for activation. Studies aimed
      at elucidating signal transduction events resulting from CB2 interaction with its
      native ligands, and of the role of exogenous cannabinoids in modulating this
      process, are providing novel insights into the role of CB2 in maintaining a
      homeostatic immune balance within the host. Furthermore, these studies suggest
      that the CB2 may serve as a selective molecular target for therapeutic
      manipulation of untoward immune responses, including those associated with a
      variety of neuropathies that exhibit a hyperinflammatory component.

PMID- 19152722
TI  - Functional oesophagoscopy: endoscopic evaluation of the oesophageal phase of
      deglutition.
AB  - BACKGROUND: The anatomy and function of the oropharynx and larynx during
      deglutition can be assessed using the flexible endoscope, but this evaluation
      does not provide information on the oesophagus. Guided observation of oesophageal
      swallowing enables extended dysphagia evaluation. OBJECTIVE: To assess the
      diagnostic utility of guided observation of oesophageal swallowing in the
      evaluation of dysphagia. STUDY DESIGN: Retrospective case series. METHODS:
      Procedures for guided observation of oesophageal swallowing were reviewed for
      oesophageal findings and compared with fluoroscopy and manometry. RESULTS: Twenty
      one patients underwent guided observation of oesophageal swallowing and
      concurrent videofluoroscopy and/or manometry. No complications of the former
      procedure occurred. The results of guided observation of oesophageal swallowing
      concurred with those of fluoroscopy in 15/21 cases (71 per cent) and with those
      of manometry in five of six (83 per cent) cases. Guided observation of
      oesophageal swallowing revealed anatomic pathology contributing to dysphagia in
      15/21 (71 per cent) patients. The procedure identified pathology not detected by
      fluoroscopy and manometry in 13/21 (62 per cent) patients. CONCLUSION: Guided
      observation of oesophageal swallowing appears to be a safe diagnostic tool with
      which to evaluate the oesophageal phase of deglutition.

PMID- 19152723
TI  - History of instruments used for mastoidectomy.
AB  - AIM: To present the historical development of specific instruments used for
      mastoidectomy and their resulting implications for this surgery. METHOD:
      Compilation of original written documents, trade catalogues and collections of
      instruments used in mastoid surgery, with a review of the secondary literature on
      the subject. RESULTS: The first surgical opening of the mastoid was performed by
      Petit in 1736 with a trepanation system. More than one and a half centuries
      later, in 1873, Schwartze codified the operation using chisels and gouges. At the
      end of the nineteenth century, Macewen introduced the electrical dental burr for
      mastoid surgery, but it remained largely unrecognised. At the beginning of the
      1950s, the systematic use of the microscope in ear surgery allowed generalised
      use of the drill and improvement of the suction-irrigation system. CONCLUSION:
      Three instrumental periods are recognisable in the history of mastoidectomy: the
      trepan period, the chisel and gouge period, and the electrical drill period.

PMID- 19152724
TI  - Pain versus bleeding risk following tonsillectomy: do patients and doctors agree?
AB  - OBJECTIVE: To investigate the differing opinions of patients and medical
      practitioners regarding the relative priorities of pain relief versus bleeding
      prevention following tonsillectomy. METHODS: Questionnaires were mailed out to
      adult patients, paediatric patients' parents, general practitioners and ENT
      surgeons. RESULTS: A total of 72/112 (64.3 per cent) questionnaires were
      returned. Adult patients, paediatric patients' parents, general practitioners and
      ENT surgeons all ranked bleeding as the most important factor when assessing
      risks related to tonsillectomy. Most adult patients indicated that they would
      accept a bleeding risk of 2 per cent; however, parents indicated that they would
      accept a higher bleeding risk (3 per cent) for their children in exchange for
      better pain control. CONCLUSIONS: Adult patients, paediatric patients' parents
      and doctors were slightly more inclined to 'trade-off' an increased post
      tonsillectomy bleeding risk in exchange for better post-tonsillectomy pain
      control, although concerns about post-operative haemorrhage remained the main
      priority for all groups.

PMID- 19152725
TI  - Suturing of Little's area of the nasal septum for epistaxis.
AB  - BACKGROUND: Epistaxis is a common condition presenting to emergency and ENT
      clinics. Most epistaxis bleeding originates from Little's area of the nasal
      septum. Some cases of refractory epistaxis cannot be resolved with packing or
      electrocoagulation. METHOD: The suturing technique applied is widely used in
      surgery. When faced with pulsatile, recurrent bleeding from Little's area of the
      nasal septum, all rhinologists should possess the skills to be able to suture the
      bleeding site, especially after failure of local cautery or packing. CASE REPORT:
      The authors have successfully treated four difficult cases of nasal bleeding from
      Little's area by suturing. CONCLUSION: This technique could eliminate the
      discomfort and complications of nasal packing. To the best of our knowledge, this
      report probably represents the first published case series of suturing of
      Little's area to treat recurrent nasal bleeding. More cases need to be treated in
      this way to enable further evaluation of the technique.

PMID- 19152726
TI  - Adenosquamous carcinoma of maxillary sinus: case showing complete response to S
      1.
AB  - BACKGROUND: Adenosquamous carcinoma is a very rare tumour which is characterised
      pathologically by the simultaneous presence of distinct areas of adenocarcinoma
      and squamous cell carcinoma. Generally, adenosquamous carcinoma has an aggressive
      clinical course and is associated with a poor prognosis. Most cases have been
      treated by surgery alone or combined with radiotherapy. Chemotherapy is rarely
      used in treating adenosquamous carcinoma, and it has been difficult to establish
      treatment guidelines due to the paucity of cases. CASE: We report a case of
      adenosquamous carcinoma which arose in the maxillary sinus of a 77-year-old man.
      Despite surgical treatment and chemoradiotherapy to the primary site, he
      developed bilateral neck metastases after the surgery. The patient was treated
      with S-1, a novel oral fluoropyrimidine anticancer agent, with a complete (albeit
      finite) response. CONCLUSION: This report presents the aggressive character of
      adenosquamous carcinoma and the possible role of S-1 in the treatment of this
      uncommon neoplasm.

PMID- 19152727
TI  - Adherence and persistence with omalizumab and fluticasone/salmeterol within a
      managed care population.
AB  - Asthma control requires adherence with pharmacologic therapy. A medication's mode
      of delivery may affect adherence. The purpose of this study was to compare
      medication persistence and adherence between patients newly treated with either
      an inhaled or injected asthma medication. Using a propensity-score-matched
      retrospective cohort study, we evaluated medication persistence and adherence
      over 1 year in adult asthma patients newly treated with omalizumab or fluticasone
      (500 microg)/salmeterol (50 microg) (FSC 500/50). Kaplan-Meier analysis was
      conducted to compare persistence between users of FSC 500/50 and omalizumab using
      the log-rank test. We conducted four sensitivity analyses. After propensity
      matching, the study sample included 213 omalizumab patients and 426 FSC 500/50
      patients, with no statistically significant differences between groups on
      baseline measures. Mean adherence rates were 64.6% for omalizumab and 29.5% for
      FSC 500/50 (p < 0.0001). Fifty-four percent of omalizumab users were persistent
      at 1 year compared with 18.5% of FSC 500/50 users (p < 0.0001). In sensitivity
      analyses, we stratified patients by evidence of allergy and the results did not
      change. Adherence was more than twice as high and persistence was almost twice as
      high among omalizumab compared with FSC 500/50 users. The direction of our
      findings was consistent across all sensitivity analyses. In both omalizumab and
      FSC 500/50 cohorts, persistence decreased substantially over 1 year. Our study
      suggests that injected medications may have advantages in asthma treatment. A
      comprehensive program to improve adherence should address not just administration
      route but also patient factors that prevent proper medication use.

PMID- 19152729
TI  - Migraine auras and the eyes of the mind.

PMID- 19152730
TI  - Therapeutic applications of repetitive transcranial magnetic stimulation in
      clinical neurorehabilitation.
AB  - Transcranial magnetic stimulation (TMS) was introduced nearly 20 years ago and
      has since been developed as a sophisticated tool for neuroscience research. It is
      an excellent technique that complements other non-invasive methods for studying
      human brain physiology. The aim of the present study was to review the basic
      concepts and principles of the repetitive TMS (rTMS) technique, gathering
      evidence of its applications in neurorehabilitation. Several clinical studies
      have reported that sessions of rTMS can improve some or all of the motor symptoms
      associated with Parkinson's disease, dystonia and stroke. However, since these
      changes are transient, it is premature to propose these applications as realistic
      therapeutic options, even though the rTMS technique has shown itself to be,
      potentially, a modulator of sensorimotor integration and neurogenesis. Future
      work in this area promises to advance our understanding of the pathophysiology of
      a wide range of neurological conditions, generate widely applicable diagnostic
      tools for clinical neurophysiology, and perhaps establish neuromodulation as a
      viable therapeutic option in neurorehabilitation.

PMID- 19152731
TI  - Charles Bonnet syndrome.
AB  - Charles Bonnet syndrome (CBS) is a disorder of visual hallucinations typically
      occurring in older patients with visual impairment or deafferentation of the
      visual cortex. In this paper, which reviews the relevant literature, the
      aetiologies, pathophysiology, and treatment of CBS are discussed. It is suggested
      that the ageing of the population, associated with an increased occurrence of
      vision and cerebral disorders, is leading to an increase in the incidence of CBS.

PMID- 19152732
TI  - Complications in major depressive disorder therapy: a review of magnetic
      resonance spectroscopy studies.
AB  - Advanced magnetic resonance imaging techniques, such as proton magnetic resonance
      spectroscopy (H-MRS), have helped to further understanding of the pathophysiology
      of major depressive disorder (MDD) and to shed light on mechanisms underlying the
      therapeutic response. Potential complications of MDD therapy constitute an
      important area of research. Interruption of the absorption of serotonin reuptake
      inhibitors (SSRIs) is associated with discontinuation syndrome, while
      electroconvulsive therapy (ECT) can lead to transient and persistent anterograde
      amnesia. This paper reviews studies, since 1994, that have used H-MRS to evaluate
      adverse effects and complications of MDD treatment, either with ECT or SSRIs.
      Three articles have been published on adverse effects and complications of MDD
      treatment and H-MRS. Two focused on the ECT-induced memory deterioration and
      showed no sign of hippocampal atrophy in MDD patients with a residual memory
      deterioration after ECT, but a significant mean increase of the signal from Cho
      containing compounds bilaterally, possibly due to an alteration of membrane
      turnover in the hippocampal region. The third paper showed that placebo-day
      Cho/Cr metabolite ratios were decreased in subjects with discontinuation
      syndrome, a finding that possibly reflects the dynamics of rostral anterior
      cingulate function. In spite of the limits deriving from the small number of
      papers published, our review demonstrated that H-MRS could be a useful instrument
      not only in evaluating therapy efficacy, but also for offering new insights into
      mechanisms underlying MDD treatments.

PMID- 19152733
TI  - Psychiatric symptoms related to the use of lamotrigine: a review of the
      literature.
AB  - Lamotrigine is an established anticonvulsant agent and also an effective
      maintenance therapy for bipolar disorder. In Italy it is approved for the
      treatment of epilepsy with partial seizures, partial seizures with secondary
      generalization and generalized seizures, both in monotherapy and as an add-on
      therapy in patients with refractory epilepsy; it is also approved for the
      prevention of depressive episodes in patients with bipolar disorder with a
      predominant depressive component. Lamotrigine is generally well tolerated;
      however, some psychiatric problems have been reported in patients using the drug
      to treat mental disorders (mainly bipolar) or epilepsy. The clinical features of
      these psychiatric side effects are: affective switches, full acute psychotic
      episodes, and hallucinations. In conclusion, lamotrigine is an effective drug,
      very useful in the therapy of epilepsy and mood disorders, but clinicians have to
      be aware of the risk that it can induce psychiatric symptoms or acute episodes.

PMID- 19152734
TI  - On the calculation of transcallosal conduction time using transcranial magnetic
      stimulation.
AB  - Transcallosal conduction time (TCT), based on the results of transcranial
      magnetic stimulation studies, is currently calculated as a function of the
      ipsilateral silent period (iSP) and of the motor evoked potential (MEP) obtained
      from a target muscle (TCTcurrent = iSP latency - MEP latency). We argue that this
      measure overestimates TCT and may lead to a bias in statistical group
      comparisons. We propose an alternative measure, TCTproposed, which we defined as
      TCTproposed = iSP latency - cSP latency, where cSP is the contralateral silent
      period. We report our results on the comparison of the two measures in twenty
      healthy individuals and provide a theoretical basis for TCTproposed.

PMID- 19152735
TI  - Pattern analysis of motor functional connectivity.
AB  - Functional connectivity among brain regions has been widely researched in terms
      of spatial maps or between-region connectivity strengths. Yet it is not easy to
      interpret the results of such research. In this paper, a pattern analysis
      framework based on the general linear model and the fuzzy c-means clustering
      algorithm is presented. This schema is applied to a real fMRI dataset from
      unilateral finger movement tasks. The patterns of connectivity between the
      associative parietal cortex and BA6, and between the cerebellum and BA6, were
      detected and demonstrated their close integration. The connectivity patterns
      between BA6 and the primary motor cortex reflected the asymmetrical motor
      function organization related to handedness. Patterns between BA6 and the primary
      sensory cortex were complicated, which reflected their highly functional
      specialization.

PMID- 19152736
TI  - Transient global amnesia: hippocampal magnetic resonance imaging abnormalities.
AB  - Transient global amnesia (TGA) is an episodic dysfunction of declarative memory
      that usually resolves within 12 hours and whose underlying pathophysiological
      mechanisms are still unclear. Recent studies, on the basis of transient focal
      high-signal abnormalities in the hippocampus on diffusion-weighted imaging (DWI),
      suggest involvement of memory circuits in the temporo-mesial region. Out of a
      total of 65 patients presenting with acute or subacute TGA between May 2004 and
      May 2008, we retrospectively analysed 21 in whom a DWI sequence was performed.
      Five patients showed a focal hippocampal signal alteration both on DWI and on
      conventional T2; this alteration was no longer detectable on follow-up MRI two
      months later. The presence of transient DWI and T2 alterations in the hippocampal
      formation suggests that TGA could have a multifactorial, non-vascular aetiology.
      The presence of local susceptibility to neuronal metabolic stress emerges as a
      likely hypothesis.

PMID- 19152737
TI  - Migraine as a process - challenges in the effective management of migraine.

PMID- 19152739
TI  - Circadian clock genes in reproductive tissues and the developing conceptus.
AB  - The circadian (near 24-h) clock is involved in the temporal organisation of
      physiological and biochemical activities of many organisms, including humans. The
      clock functions through the rhythmic transcription and translation of several
      genes, forming an oscillatory feedback loop. Genetic analysis has shown that the
      circadian clock exists in both a central circadian pacemaker (i.e. the
      suprachiasmatic nucleus of the hypothalamus), as well as in most peripheral
      tissues. In particular, the circadian clockwork genes are expressed in all female
      and male reproductive tissues studied so far, as well as in the conceptus itself.
      The current data clearly show a robust rhythm in female reproductive tissues, but
      whether rhythmicity also exists in male reproductive tissues remains uncertain.
      Although the conceptus also expresses most of the canonical circadian genes, the
      rhythmicity of their expression is still under investigation. Published data
      indicate that environmental and genetic manipulations influence reproductive
      function and fecundity, suggesting an important role for the circadian clock in
      reproduction, and possibly early development.

PMID- 19152740
TI  - Telomeres and reproductive aging.
AB  - Infertility, miscarriage and aneuploid offspring increase with age in women, and
      meiotic dysfunction underlies reproductive aging. How aging disrupts meiotic
      function in women remains unclear, but as women increasingly delay having
      children, solving this problem becomes an urgent priority. Telomeres consist of a
      (TTAGGG)(n) repeated sequence and associated proteins at chromosome ends, mediate
      aging in mitotic cells and may also mediate aging during meiosis. Telomeres
      shorten both during DNA replication and from the response to oxidative DNA
      damage. Oocytes do not divide in adult mammals, but their precursors do replicate
      during fetal oogenesis; eggs ovulated from older females have traversed more
      mitotic cell cycles before entering meiosis during fetal oogenesis than eggs
      ovulated from younger females. Telomeres also would be expected to shorten from
      inefficient DNA repair of oxidative damage, because the interval between fetal
      oogenesis and ovulation is exceptionally prolonged in women. We have tested the
      hypothesis that telomere shortening disrupts meiosis by shortening telomeres
      experimentally in mice, which normally do not exhibit age-related meiotic
      dysfunction. Interestingly, mouse telomeres are much longer than human telomeres,
      but genetic or pharmacological shortening of mouse telomeres recapitulates in
      mice the human reproductive aging phenotype as the mouse telomeres reach the
      length of telomeres from older women. These observations led us to propose a
      telomere theory of reproductive aging. Moreover, chronological oxidative stress
      increases with reproductive aging, leading to DNA damage preferentially at
      (TTAGGG)(n) repeats. Finally, if telomeres shorten with aging, how do they reset
      across generations? Telomerase could not play a significant role in telomere
      elongation during early development, because this enzyme is not active until the
      blastocyst stage, well after the stage when telomere elongation takes place.
      Rather, telomeres lengthen during the early cell cycles of development by a novel
      mechanism involving recombination and sister chromatid exchange. Telomere
      dysfunction resulting from oxidative stress, a DNA damage response or aberrant
      telomere recombination may contribute to reproductive aging-associated meiotic
      defects, miscarriage and infertility.

PMID- 19152741
TI  - Spermatogonial stem cells: unlimited potential.
AB  - Recent reports have demonstrated that adult cells can be reprogrammed to
      pluripotency, but mostly with genes delivered using retroviruses. Some of the
      genes are cancer causing; thus, these adult-derived embryonic stem (ES)-like
      cells cannot be used for therapy to cure human diseases. Remarkably, it has also
      been demonstrated recently by several groups that, in mice, spermatogonial stem
      cells (SSCs) can be reprogrammed to ES-like cells without the necessity of
      exogenously added genes. SSCs constitute one of the most important stem cell
      systems in the body, not only because they produce spermatozoa that transmit
      genetic information from generation to generation, but also because of the recent
      studies showing their remarkable plasticity. Very little is known about SSCs in
      humans, except for the earlier work of Clermont and colleagues who demonstrated
      that there are A(dark) and A(pale) spermatogonia, with the A(dark) referred to as
      the reserve stem cells and the A(pale) being the renewing stem cells. We now
      demonstrate that G protein-coupled receptor 125 (GPR125) may be a marker for
      human SSCs. Putative human SSCs can also be reprogrammed to pluripotency. We were
      able to achieve this result without the addition of genes, suggesting that human
      SSCs have considerable potential for cell-based, autologous organ regeneration
      therapy for various diseases.

PMID- 19152742
TI  - Embryonic gene expression profiling using microarray analysis.
AB  - Microarray technology enables the interrogation of thousands of genes at one time
      and therefore a systems level of analysis. Recent advances in the amplification
      of RNA, genome sequencing and annotation, and the lower cost of developing
      microarrays or purchasing them commercially, have facilitated the analysis of
      single preimplantation embryos. The present review discusses the components of
      embryonic expression profiling and examines current research that has used
      microarrays to study the effects of in vitro production and nuclear transfer.

PMID- 19152743
TI  - Genetic modification for bimaternal embryo development.
AB  - Full mammalian development typically requires genomes from both the oocyte and
      spermatozoon. Biparental reproduction is necessary because of parent-specific
      epigenetic modification of the genome during gametogenesis; that is, a maternal
      methylation imprint imposed during the oocyte growth period and a paternal
      methylation imprint imposed in pregonadal gonocytes. This leads to unequivalent
      expression of imprinted genes from the maternal and paternal alleles in embryos
      and individuals. It is possible to hypothesise that the maternal methylation
      imprint is necessary to prevent parthenogenesis, which extinguishes the
      opportunity for having descendents, whereas the paternal methylation imprint
      prevents parthenogenesis, ensuring that a paternal contribution is obligatory for
      any descendants. To date, there are several lines of direct evidence that the
      epigenetic modifications that occur during oocyte growth have a decisive effect
      on mammalian development. Using bimaternal embryos with two sets of maternal
      genomes, the present paper illustrates how parental methylation imprints are an
      obstacle to the progression of parthenogenesis.

PMID- 19152744
TI  - Nuclear transfer and oocyte cryopreservation.
AB  - Somatic cells can be reprogrammed to a totipotent state through nuclear transfer
      or cloning, because it has been demonstrated that the oocyte has the ability to
      reprogramme an adult nucleus into an embryonic state that can initiate the
      development of a new organism. Therapeutic cloning, whereby nuclear transfer is
      used to derive patient-specific embryonic stem cells, embraces an entire new
      opportunity for regenerative medicine. However, a key obstacle for human
      therapeutic cloning is that the source of fresh human oocytes is extremely
      limited. In the present review, we propose prospective sources of human oocytes
      by using oocyte cryopreservation, such as an oocyte bank and immature oocytes. We
      also address some potential issues associated with nuclear transfer when using
      cryopreserved oocytes. In the future, if the efficacy and efficiency of
      cryopreserved oocytes are comparable to those of fresh oocytes in human
      therapeutic cloning, the use of cryopreserved oocytes would be invaluable and
      generate a great impact to regenerative medicine.

PMID- 19152745
TI  - Cryopreservation of manipulated embryos: tackling the double jeopardy.
AB  - The aim of the present review is to provide information to researchers and
      practitioners concerning the reasons for the altered viability and the medium-
      and long-term consequences of cryopreservation of manipulated mammalian embryos.
      Embryo manipulation is defined herein as the act or process of manipulating
      mammalian embryos, including superovulation, AI, IVM, IVF, in vitro culture,
      intracytoplasmic sperm injection, embryo biopsy or splitting, somatic cell
      nuclear transfer cloning, the production of sexed embryos (by sperm sexing),
      embryo cryopreservation, embryo transfer or the creation of genetically modified
      (transgenic) embryos. With advances in manipulation technologies, the application
      of embryo manipulation will become more frequent; the proper prevention and
      management of the resulting alterations will be crucial in establishing an
      economically viable animal breeding technology.

PMID- 19152746
TI  - Altered gene expression in cloned piglets.
AB  - Studies on cloned pigs are scant compared with those in mice and cattle.
      Expression profiles of cloned pig embryos on full-term cloned pigs are even more
      limited owing to the limited availability of DNA microarray technology in the
      pig. We have conducted expression profile comparisons between pigs from somatic
      cell nuclear transfer and pigs from conventional breeding at birth and 1 month of
      age. Differentially expressed genes that are subjected to DNA methylation were
      also examined for their DNA methylation status. These data will be presented in
      the 2009 Annual Meeting of the International Embryo Transfer Society in San
      Diego. In the present review, we focus on summarising existing findings on
      epigenetic and other changes in cloned embryo, cloned pigs and their offspring by
      conventional breeding.

PMID- 19152747
TI  - Transcriptional heterogeneity in mouse embryonic stem cells.
AB  - The embryonic stem (ES) cell is a stem cell derived from early embryos that can
      indefinitely repeat self-renewing cell division cycles as an undifferentiated
      cell in vitro and give rise to all specialised cell types in the body. However,
      manipulating ES cell differentiation in vitro is a challenge due to, at least in
      part, heterogeneous gene induction. Recent experimental evidence has demonstrated
      that undifferentiated mouse ES cells maintained in culture exhibit heterogeneous
      expression of Dppa3, Nanog, Rex1, Pecam1 and Zscan4 as well as genes
      (Brachyury/T, Rhox6/9 and Twist2) normally expressed in specialised cell types.
      The Nanog-negative, Rex1-negative or T-positive ES cell subpopulation has a
      unique differentiation potential. Thus, studying the mechanism that generates ES
      cell subpopulations will improve manipulation of ES cell fate and help our
      understanding of the nature of embryonic development.

PMID- 19152748
TI  - Cloning endangered felids using heterospecific donor oocytes and interspecies
      embryo transfer.
AB  - Somatic cell nuclear transfer (SCNT) offers the possibility of preserving
      endangered species. It is one of the few technologies that avoids the loss of
      genetic variation and provides the prospect of species continuance, rather than
      extinction. Nonetheless, there has been a debate over the use of SCNT for
      preserving endangered species because of abnormal nuclear reprogramming, low
      efficiency and the involvement of extra mitochondrial DNA (mtDNA) of a different
      species in live offspring produced by interspecies SCNT. Despite these
      limitations, live endangered cloned animals have been produced. In the present
      paper, we describe recent research on the production of cloned embryos derived by
      fusion of wild felid fibroblast cells with heterospecific domestic cat cytoplasts
      and their viability after transfer into domestic cat recipients. In addition, we
      discuss epigenetic events that take place in donor cells and felid cloned embryos
      and mtDNA inheritance in wild felid clones and their offspring.

PMID- 19152749
TI  - Cloning from stem cells: different lineages, different species, same story.
AB  - Following nuclear transfer (NT), the most stringent measure of extensive donor
      cell reprogramming is development into viable offspring. This is referred to as
      cloning efficiency and quantified as the proportion of cloned embryos transferred
      into surrogate mothers that survive into adulthood. Cloning efficiency depends on
      the ability of the enucleated recipient cell to carry out the reprogramming
      reactions ('reprogramming ability') and the ability of the nuclear donor cell to
      be reprogrammed ('reprogrammability'). It has been postulated that
      reprogrammability of the somatic donor cell epigenome is inversely proportional
      to its differentiation status. In order to test this hypothesis,
      reprogrammability was compared between undifferentiated stem cells and their
      differentiated isogenic progeny. In the mouse, cells of divergent differentiation
      status from the neuronal, haematopoietic and skin epithelial lineage were tested.
      In cattle and deer, skeletal muscle and antler cells, respectively, were used as
      donors. No conclusive correlation between differentiation status and cloning
      efficiency was found, indicating that somatic donor cell type may not be the
      limiting factor for cloning success. This may reflect technical limitations of
      the NT-induced reprogramming assay. Alternatively, differentiation status and
      reprogrammability may be unrelated, making all cells equally difficult to
      reprogramme once they have left the ground state of pluripotency.

PMID- 19152750
TI  - A decade of progress since the birth of Dolly.
AB  - The greatest effect of the birth Dolly, the first cloned animal derived from an
      adult, has been in prompting biologists to consider ways of reprogramming adult
      nuclei to a pluripotent state directly. The first procedure depends upon use of
      viral vectors to introduce selected transcription factors, but this procedure is
      slow and very inefficient. Research in our laboratory has demonstrated that
      exposure of differentiated nuclei to an extract of embryo stem cells induces
      expression of key pluripotency genes within 8 h, suggesting that it may be
      possible to identify and use other factors to enhance direct reprogramming. A
      study of mechanisms that bring about changes in DNA methylation in early sheep
      embryos identified a developmental isoform of Dnmt1, the expression of which was
      limited to early stages of pregnancy. Reduction in the level of transcript of
      this isoform at the time of fertilisation caused sheep embryo development to
      cease at the early morula stage, revealing a key role for the isoform that
      remains to be characterised. The ability to obtain pluripotent cells from
      specific patients is providing important new opportunities to study inherited
      diseases when the causative mutation is not known. The initial objective of this
      research is not cell therapy, but to use cells with the characteristics of those
      in a patient who has inherited the disease to establish a high-throughput screen
      to identify drugs that are able to prevent progression of the symptoms of the
      disease. Research is in progress with cells from patients with amyotropic lateral
      sclerosis.

PMID- 19152751
TI  - From gametes to stem cells and back: basic biology and emerging applications.
      Proceedings of the Annual Conference of the International Embryo Transfer
      Society. January 3-7, 2009. San Diego, California, USA.

PMID- 19152771
TI  - [Arterial-hypertension prevalence in the general population of Martinique].
AB  - BACKGROUND: Since 1996, arterial hypertension has been recognized as one of the
      main health priorities in Martinique. However, its prevalence in the general
      population has never been measured. Furthermore, obesity is increasing in many
      countries and studies have shown that hypertension is more frequent in obese
      people than in people with normal body mass index. The objective of this survey
      is to measure hypertension prevalence in the general population and to study the
      link between hypertension, weight status and socioeconomic level. METHODS: Cross
      sectional study of randomly selected homes in randomly selected geographical
      islets. All household members in these homes constituted the eligible population.
      Arterial hypertension was defined as systolic pressure greater than 140mmHg
      and/or diastolic pressure greater than 90mmHg and/or antihypertensive treatment.
      Weight status was estimated using the body mass index. RESULTS: Study concerned
      1504 persons aged 16 years or older with a sex-ratio of 0.7 and an average age of
      48.3 years for men and 48.5 years for women, p=0.88. The prevalence rate of
      hypertension is 29% [IC(95%): 25.9-31.8] in the sample and declines to 22.5%
      [IC(95%): 20.1-25.1] using weighted data. The prevalence rate is 33.1% [IC(95%):
      30.2-36.6] for overweight and 20.1% [IC(95%): 17.8-22.6] for obesity. Being
      overweight is more frequent among persons with hypertension than among ones with
      normal blood pressure, 73.0 versus 47.4%; p<0.001. In those with hypertension,
      overweight does not differ significantly between men and women, but the
      prevalence of obesity is greater among women than among men (35.7 versus 20.6 %,
      p<0.05). CONCLUSION: The high prevalence of both hypertension and obesity in the
      general Martinican population has been confirmed by this study. Prevention
      actions are required to decrease the cardiovascular risk in this population.

PMID- 19152772
TI  - Functional magnetic resonance imaging reference phantom.
AB  - Functional magnetic resonance imaging (fMRI) is widely used to pinpoint active
      brain areas. Changes in neuronal activity modulate the local blood oxygenation
      level, and the associated modulation of the magnetic field homogeneity can be
      detected with magnetic resonance imaging. Thus, the blood oxygenation level
      dependent (BOLD) fMRI indirectly measures neuronal activity. Similar modulation
      of magnetic field homogeneity was here elicited by other means to generate a BOLD
      like change in a new phantom constructed to provide reference activations during
      fMRI. Magnetic inhomogeneities were produced by applying current to coils located
      near the phantom containing 1.5 ml of Gd-doped water. The signal-to-noise ratio
      of the images, produced by gradient-recalled echo-planar imaging, varied between
      104 and 107 at a selected voxel when the field was and was not inhomogenized,
      respectively. The contrast of signals between homogeneous and inhomogeneous
      conditions was generally stable, except in 3% of time points. During the periods
      of greatest deviations an observable change would have been detected in a
      simultaneously measured BOLD signal. Such changes could result from the imaging
      method or occur through glitches in hardware or alterations in the measurement
      environment. With identical measurement setups, the phantom could allow comparing
      intersession or intersubject brain activations.

PMID- 19152773
TI  - Alteration of diffusion tensor parameters in postmortem brain.
AB  - In autopsy of humans, there is usually an interval of hours to days between death
      and tissue fixation, during which the cadaver is stored below room temperature to
      retard tissue autolysis. We have attempted to model this process and evaluate the
      alteration in diffusion indices of the postmortem brain in pigs, which were kept
      at 4 degrees C. The pigs were scanned prior to death and at 3, 6, 9, 12, 18, 24,
      30, 36, 42, 48 and 72 h postmortem. Regions of interest were placed in the corpus
      callosum, internal capsule, periventricular and subcortical white matter
      anteriorly and posteriorly. There was a slight increase in fractional anisotropy
      (FA) in the first 3 h postmortem. The FA remained stable up to 72 h postmortem.
      There was a marked decrease in trace, eigenmajor (lambda major), eigenmedium
      (lambda medium) and eigenminor (lambda minor), particularly in the first 3 h
      following death. This study supports the utility of measuring diffusion
      anisotropy if the time elapsed between death and tissue fixation is within 3
      days. However, trace and eigenvalues decreased markedly within the first few
      hours postmortem. Therefore trace and eigenvalues obtained from ex vivo studies
      cannot be extrapolated to in vivo studies.

PMID- 19152774
TI  - Quantitative intact specimen magnetic resonance microscopy at 3.0 T.
AB  - In this report, we discuss the application of a methodology for high-contrast,
      high-resolution magnetic resonance microscopy (MRM) of murine tissue using a 3.0
      T imaging system. We employed a threefold strategy that included customized
      specimen preparation to maximize image contrast, three-dimensional data
      acquisition to minimize scan time and custom radiofrequency resonator design to
      maximize signal sensitivity. Images had a resolution of 100 x 78 x 78 microm(3)
      with a signal-to-noise ratio per voxel greater than 25:1 and excellent contrast
      to-noise ratios over a 30-min acquisition. We quantitatively validated the
      methods through comparisons of neuroanatomy across two lines of genetically
      engineered mice. Specifically, we were able to detect volumetric differences of
      as little as 9% between genetically engineered mouse strains in multiple brain
      regions that were predictive of underlying impairments in brain development. The
      overall methodology was straightforward to implement and provides ready access to
      basic MRM at field strengths that are widely available in both the laboratory and
      the clinic.

PMID- 19152775
TI  - Free-breathing 3-dimensional steady-state free precession coronary magnetic
      resonance angiography: comparison of four navigator gating techniques.
AB  - This work compared the performance of four navigator gating algorithms
      [accept/reject (A/R), diminishing variance algorithm (DVA), phase ordering with
      automatic window selection (PAWS) and retrospective gating (RETRO)] in
      suppressing respiratory motion artifacts in free-breathing 3D balanced steady
      state free precession coronary MRA. In 10 volunteers, the right coronary artery
      (RCA) or the left anterior descending artery (LAD) was imaged (both if time
      permitted) at 1.5 T with the four gating techniques in random order. Vessel
      signal, vessel contrast and motion suppression were scored by the consensus of
      two blinded readers. In 15 imaged vessels (nine RCA and six LAD), PAWS provided
      significantly better image quality than A/R (P<.05), DVA (P=.02) and RETRO
      (P=.002). While the quality difference between A/R and DVA was not statistically
      significant, both algorithms yielded significantly better image quality than
      RETRO. PAWS and DVA were the most efficient algorithms, providing an
      approximately 20% and 40% relative increase in average navigator efficiency
      compared to A/R and RETRO, respectively.

PMID- 19152776
TI  - [Dyspnea and handicap in chronic obstructive pulmonary disease: interaction of
      their mechanisms].
AB  - Today, dyspnea in chronic obstructive pulmonary disease (COPD) is attributed to
      thoracic distention secondary to bronchial obstruction and hyperventilation. It
      inevitably occurs during exercise, even in patients with little obstruction, when
      they are capable of the elevated and prolonged power output that necessitates
      substantial hyperventilation. Exercise intolerance is due mainly to dyspnea, but
      muscle fatigue is also involved, especially in COPD patients who are
      malnourished. Deterioration of muscle function follows a substantial reduction in
      daily physical activity. In malnourished and hypoxemic subjects, however,
      responsibility for this is attributed to diverse aggravating biological processes
      related to chronic low-grade inflammation and to accentuated oxidative stress.
      The drastic diminution of physical activity results from ventilatory and muscle
      impairment and from symptoms that make movement painful. Improvement of
      ventilatory and muscle function, however, does not lead to recovery that allows
      sufficient physical activity. The spiral of disengagement, a morbid,
      psychodynamic process, accompanies chronic diseases and has the strongest effect
      in patients who were not highly physically active before becoming ill.
      Improvement of this handicap therefore requires a comprehensive management of
      patients, not confined to the prescription of physical activity under medical
      supervision. The aim is to offer diverse treatment propositions that can produce
      sustainable behavioral change.

PMID- 19152777
TI  - [Prescribe clean intermittent self-catheterization].
AB  - Clean intermittent self-catheterization is the recommended mode of voiding in
      patients with urinary retention. CISC is a non-sterile catheterization, done by
      the patient himself to insure complete emptying of the bladder several times per
      day. Its prescription rests on well-established recommendations with a sufficient
      frequency of self-catheterization (minimum 4), collected volumes less than 400 mL
      and a diuresis higher than 1.5 L. Clean intermittent self-catheterization allows
      a reduction in complications of infection, protects the upper urinary tract and
      provides urinary continence for the patient. Asymptomatic bacteriuria is very
      frequent in patients treated with intermittent catheterization and does not
      justify antibiotic therapy. Only symptomatic urinary tract infections have to be
      treated by a short course of antibiotics. Patient education and personalized
      medical follow-up must ensure adapted management dependant on this voiding mode
      and its risk factors. A guideline is provided to prescribe clean intermittent
      self-catheterization with its indications, its advantages and complications, its
      medical surveillance and treatment of urinary tract infection. This procedure
      should be well-known to general practitioners who are responsible for the follow
      up of these patients.

PMID- 19152778
TI  - Severe acute ulcerated gastritis induced by salt.

PMID- 19152779
TI  - Influence of anesthetics on pharyngeal flap surgery: a 23-year study.
AB  - This study assessed the influence of anesthetics on early complications after
      pharyngeal flap surgery. A 23-year retrospective chart review was carried out of
      all patients at the authors' institution who underwent superiorly based
      pharyngeal flap surgery. Variables analyzed were gender, age at the time of
      surgery, cleft type, anesthesia procedure used and complications in the early
      postoperative period. 2299 patients (50% male; 50% female) who underwent
      pharyngeal flap surgery between 1980 and 2003 were reviewed. The highest number
      of surgeries was performed in patients aged 11-20 years. There were 1042 patients
      with at least one type of complication. Of these, 39 required reoperation to
      control complications such as bleeding and airway obstruction. There were no
      records of death. Vomiting and pain were the most frequent postoperative
      complications (16% and 14% of patients, respectively). Lower complication rates
      were observed when anesthesia protocols included sevoflurane, propofol and
      opioids.

PMID- 19152780
TI  - Reaction mixtures based on the CTAB-Dodecyl Epoxide-water microemulsion for the
      synthesis of novel Nucleo-Lipids.
AB  - Nucleotide-functionalized amphiphiles can be generated in an aqueous
      microemulsion based on the cationic surfactant CetylTrimethylAmmonium Bromide
      (CTAB). The lipophilic precursor, Dodecyl Epoxide (DE), was able to
      hydrophobically modify several types of nucleotides (NMPs) giving rise to the
      production of novel anionic Nucleo-Lipids (NL), through a ring-opening reaction
      occurring at level of the CTAB micellar interface. The coexistence of both
      cationic (CTAB) and NL monomers triggered the spontaneous formation of aqueous
      suspensions of onion-like aggregates, as confirmed by optical microscopy and
      spectroturbidimetry. The solubilization process of DE into CTAB micellar phase in
      the presence of NMPs was first characterised through conductometry. DLS data
      showed a gradual micellar swelling resulting in a higher oil uptake upon addition
      of NMPs in the starting liquid L(1) phase. An important result achieved in this
      study was obtained through the inspection of long-aged suspensions incubated with
      each of four different types of NMPs, including their binary equimolar
      combinations. Samples made with the complementary pairs AU and CG showed up very
      stable vesicular systems, unlike the other random base paired mixtures, where we
      found a coexistence of liquid crystalline domains in equilibrium with either
      transparent liquid phases or dense isotropic gel phases. The potential role of
      the molecular recognition on the self-assembly properties of NL monomers has been
      discussed.

PMID- 19152781
TI  - Adsorption of phosphate from aqueous solutions onto modified wheat residue:
      characteristics, kinetic and column studies.
AB  - Kinetic and column adsorption of phosphate from aqueous solution using modified
      wheat residue (MWS) as an adsorbent were studied in a batch reactor. The
      respective characteristic rate constants and activation energy were presented
      after linear and non-linear fitting. In addition, the effects of influent
      concentration of phosphate and flow rates on the column adsorption were also
      investigated. The results showed that the adsorption process could reach
      equilibrium in 10-15 min, and the pseudo-second-order equation generated the best
      agreement with experimental data for adsorption systems. The activation energy
      was 3.39 kJ mol(-1) indicating that the synthesis process was a physical
      adsorption. In the column tests, the increase of influent concentration and flow
      rate both decreased the breakthrough time, and the MWS-packed column exhibited
      excellent phosphate removal from aqueous solution. These results provide strong
      evidence of the potential of MWS for the technological applications of phosphate
      removal from aqueous solutions.

PMID- 19152782
TI  - Kinetic study on the binding of lectin to mannose residues in a polymer brush.
AB  - A disulfide-carrying polymer with many pendent mannose residues (dithiolated
      poly(2-methacryloyloxyethyl D-mannopyranoside)) was obtained by atom transfer
      radical polymerization (ATRP) method using 2-(2'-bromoisobutyroyloxy)ethyl
      disulfide as initiator. The obtained disulfide-carrying glycopolymer (DT-PMEMan)
      was accumulated as a polymer brush on a colloidal gold-immobilized glass
      substrate, and the binding processes of a lectin, Concanavalin A (Con A), to
      mannose residues in the polymer brush were examined using a UV-vis
      spectrophotometer with the help of a localized surface plasmon resonance. Con A
      showed a concentration-dependent specific binding to the glycopolymer brush, and
      the apparent association constant of Con A with mannose residues in the brush was
      much larger than the association constant for small sugars due to the so-called
      cluster effect. Furthermore, the glycopolymer brush-coated device had a detection
      limit lower than 5 nM. The glycopolymer-carrying device examined here is expected
      to expand our knowledge of recognition phenomena at the surface of polymer
      brushes.

PMID- 19152783
TI  - Ultrasensitive enhanced chemiluminescence enzyme immunoassay for the
      determination of alpha-fetoprotein amplified by double-codified gold
      nanoparticles labels.
AB  - A novel enhanced chemiluminescent (CL) immunoassay for ultrasensitive
      determination of alpha-fetoprotein (AFP) was reported. The method made full use
      of 4-(4'-iodo)phenylphenol (IPP) as a new potential signal enhancer and double
      codified gold nanoparticles (DC-AuNPs) labels modified with horseradish
      peroxidase (HRP)-conjugated anti-AFP used for further signal amplification. This
      protocol involved a sandwich format, in which the antigen in the sample was first
      captured by the immobilized primary antibody on the surface of magnetic beads,
      and then recognized by the second antibody labeled with DC-AuNPs. The combination
      of the remarkable sensitivity of the enhanced CL method and the use of AuNPs as
      an anti-AFP-HRP carrier for the enzymatic signal amplification, provided a linear
      response range of AFP from 0.008 to 0.3 ng mL(-1) with an extremely low detection
      limit of 5 pg mL(-1), much lower than those achieved by the classical enzyme
      linked immunosorbent assay (ELISA). This new system can be easily extended to a
      variety of immunodetection as well as DNA analysis.

PMID- 19152784
TI  - Blurring the edges in vertebrate sex determination.
AB  - Sex in vertebrates is determined by genetically or environmentally based signals.
      These signals initiate molecular cascades and cell-cell interactions within the
      gonad that lead to the adoption of the male or female fate. Previously,
      genetically and environmentally based mechanisms were thought to be distinct, but
      this idea is fading as a result of the unexpected discovery of coincident genetic
      and thermal influences within single species. Together with accumulating
      phylogenetic evidence of frequent transitions between sex-determining mechanisms,
      these findings suggest that genetic and environmental sex determination actually
      represent points on a continuum rather than discrete categories, and that
      populations may shift in one direction or the other in response to mutations or
      changing ecological conditions. Elucidation of the underlying molecular basis of
      sex determination in mice has yielded a bistable model of mutually antagonistic
      signaling pathways and feedback regulatory loops. This system would be highly
      responsive to changes in the upstream primary signal and may provide a basis for
      the rapid evolution of and transitions between different methods of sex
      determination.

PMID- 19152785
TI  - Genomics and the evolutionary origins of nervous system complexity.
AB  - Advances in genomics are leading to increased understanding of the evolution of
      complexity, especially by beginning to bridge genotype and phenotype. Here, using
      examples from nervous system evolution, we define general patterns of increased
      complexity seen across levels of biological organization. We also explore
      specific evolutionary mechanisms that increase complexity, namely those that
      increase the number of biological units (parts) in a system. We provide specific
      neurobiological examples of increased complexity in genes, gene networks, cell
      types, and tissues/organs. These examples illustrate that while a variety of
      different mechanisms increase biological complexity, they can be understood in a
      generalized comparative framework.

PMID- 19152786
TI  - Synthesis and 5-lipoxygenase inhibitory activity of new cinnamoyl and caffeoyl
      clusters.
AB  - Novel cinnamoyl and caffeoyl clusters were synthesized by multiple Cu(I)
      catalyzed [1,3]-dipolar cycloadditions and their anti-5-lipoxygenase inhibitory
      activity was tested. Caffeoyl cluster showed an improved 5-lipoxygenase
      inhibitory activity compared to caffeic acid, with caffeoyl trimer 16 and
      tetramer 19 showing the best 5-lipoxygenase inhibitory activity.

PMID- 19152787
TI  - Identification of a series of benzoxazoles as potent 5-HT6 ligands.
AB  - As part of our continuing efforts to identify therapeutics for CNS diseases such
      as schizophrenia and Alzheimer's disease (AD), we have been focused on the 5
      HT(6) receptor in order to identify potent and selective ligands as a potential
      treatment for cognitive dysfunction. Herein we report the identification of a
      novel series of benzoxazole derivatives as potent 5-HT(6) ligands. The synthesis
      and detailed SAR of this class of compounds are reported. The compounds have been
      shown to be full antagonists in a cyclic AMP functional assay.

PMID- 19152788
TI  - Solidification mechanisms of chitosan-glycerol phosphate/blood implant for
      articular cartilage repair.
AB  - OBJECTIVE: Chitosan-glycerol phosphate (chitosan-GP) is a unique polymer solution
      that is mixed with whole blood and solidified over microfractured or drilled
      articular cartilage defects in order to elicit a more hyaline repair cartilage.
      For clinical ease-of-use, a faster in situ solidification is preferred.
      Therefore, we investigated the mechanisms underlying chitosan-GP/blood implant
      solidification. METHODS: In vitro solidification of chitosan-GP/blood mixtures,
      with or without added clotting factors, was evaluated by thromboelastography.
      Serum was analyzed for the onset of thrombin, platelet, and FXIII activation. In
      vivo solidification of chitosan-GP/blood mixtures, with and without clotting
      factors, was evaluated in microdrilled cartilage defects of adult rabbits (N=41
      defects). RESULTS: Chitosan-GP/blood clots solidified in an atypical biphasic
      manner, with higher initial viscosity and minor platelet activation followed by
      the development of clot tensile strength concomitant with thrombin generation,
      burst platelet and FXIII activation. Whole blood and chitosan-GP/blood clots
      developed a similar final clot tensile strength, while polymer-blood clots showed
      a unique, sustained platelet factor release and greater resistance to lysis by
      tissue plasminogen activator. Thrombin, tissue factor (TF), and recombinant human
      activated factor VII (rhFVIIa) accelerated chitosan-GP/blood solidification in
      vitro (P<0.05). Pre-application of thrombin or rhFVIIa+TF to the surface of
      drilled cartilage defects accelerated implant solidification in vivo (P<0.05).
      CONCLUSIONS: Chitosan-GP/blood implants solidify through coagulation mechanisms
      involving thrombin generation, platelet activation and fibrin polymerization,
      leading to a dual fibrin-polysaccharide clot scaffold that resists lysis and is
      physically more stable than normal blood clots. Clotting factors have the
      potential to enhance the practical use, the residency, and therapeutic activity
      of polymer-blood implants.

PMID- 19152789
TI  - [Bipolar forearm dislocation or floating forearm (a case report)].
AB  - Bipolar dislocation of the forearm or floating forearm is a rare injury. It
      combines concomitant elbow and wrist dislocation. Only six cases have been
      reported in the literature. The diagnosis of wrist dislocation may initially be
      missed and therefore the prognosis will be worse. The authors report a case of a
      bipolar dislocation with a posterior dislocation of the elbow and a perilunate
      dislocation of the wrist.

PMID- 19152790
TI  - History of forensic medicine in Turkey.
AB  - Turkey has a short history of forensic medicine compared to the developed
      countries. Sultan Mahmud II established the first medical school of the Ottoman
      Empire named as Mekteb-i Tibbiye-i Sahane to provide health services to the army
      in 1839 [Gok S. Tomorrow, today and yesterday of the forensic medicine. 1st ed.
      Istanbul: Temel printing office; 1995]. It is also accepted as an important
      milestone of both medical education and forensic medicine in Turkey [Gok S and
      Ozen C. History and organization of forensic. 1st ed. Istanbul: Istanbul
      University Cerrahpasa Medical School Publications; 1982]. The first lecturer of
      forensic medicine at Mekteb-i Tibbiye-i Sahane was Dr. Charles Ambroise Bernard
      (C.A.). and he was also the first to perform autopsy in the history of Ottoman
      Empire [Gok, 1995]. Approximately 40 years after the first forensic medicine
      lecture in 1879, the Department of Medical Jurisprudence was established as a
      division of Zabita Tababet-i Adliye (Law Enforcement Office) in Istanbul
      [Sehsuvaroglu and Ozen. History and development of forensic medicine in the world
      and in our country. Mag Istanbul Univ Med Fac 1974;36(60)]. This paper documents
      the first two cases of autopsies performed in Turkey with the original papers
      from the National Library.

PMID- 19152791
TI  - Suite of finite element algorithms for accurate computation of soft tissue
      deformation for surgical simulation.
AB  - Real time computation of soft tissue deformation is important for the use of
      augmented reality devices and for providing haptic feedback during operation or
      surgeon training. This requires algorithms that are fast, accurate and can handle
      material nonlinearities and large deformations. A set of such algorithms is
      presented in this paper, starting with the finite element formulation and the
      integration scheme used and addressing common problems such as hourglass control
      and locking. The computation examples presented prove that by using these
      algorithms, real time computations become possible without sacrificing the
      accuracy of the results. For a brain model having more than 7,000 degrees of
      freedom, we computed the reaction forces due to indentation with frequency of
      around 1,000 Hz using a standard dual core PC. Similarly, we conducted simulation
      of brain shift using a model with more than 50,000 degrees of freedom in less
      than one minute. The speed benefits of our models result from combining the Total
      Lagrangian formulation with explicit time integration and low order finite
      elements.

PMID- 19152792
TI  - Collagen telopeptide (serum CTX) and its relationship with the size and number of
      lesions in osteonecrosis of the jaws in cancer patients on intravenous
      bisphosphonates.

PMID- 19152793
TI  - Sequence assembly.
AB  - Despite the rapidly increasing number of sequenced and re-sequenced genomes, many
      issues regarding the computational assembly of large-scale sequencing data have
      remain unresolved. Computational assembly is crucial in large genome projects as
      well for the evolving high-throughput technologies and plays an important role in
      processing the information generated by these methods. Here, we provide a
      comprehensive overview of the current publicly available sequence assembly
      programs. We describe the basic principles of computational assembly along with
      the main concerns, such as repetitive sequences in genomic DNA, highly expressed
      genes and alternative transcripts in EST sequences. We summarize existing
      comparisons of different assemblers and provide a detailed descriptions and
      directions for download of assembly programs at:
      http://genome.ku.dk/resources/assembly/methods.html.

PMID- 19152794
TI  - Neuropeptides in the rat corpus cavernosum and seminal vesicle: effects of age
      and two types of diabetes.
AB  - AIMS: To observe the development of neuropathic changes in two types of
      experimental diabetes using changes in concentrations of NPY, CGRP and amines in
      the corpora cavernosa and seminal vesicles. Type I diabetes was studied in Wistar
      rats after 12 and 16 weeks of STZ-induced hyperglycaemia, and Type II diabetes
      was studied in prediabetic GK rats aged 52 weeks. Both were compared with age
      matched normal Wistar rats. METHODS: NPY and CGRP were estimated using
      radioimmunoassay, and amines using HPLC. RESULTS: There were significant changes
      in [CGRP] in the normal corpus cavernosum and in [NPY] in the normal seminal
      vesicle with age. STZ-diabetes, induced at 10 weeks of age, resulted in
      significant elevation of [NPY] and [CGRP] in the corpora cavernosa and seminal
      vesicles after 12 and 16 weeks of hyperglycaemia, relative to age-matched control
      rats. The GK rats were intolerant of glucose at 52 weeks of age, but did not have
      raised fasting blood glucose levels. [NPY], [CGRP] and [noradrenaline] in corpora
      cavernosa were significantly increased in the prediabetic GK animals relative to
      age-matched Wistar control rats. The seminal vesicles of GK rats showed a
      significant increase in [NPY], a non-significant increase in [CGRP], and a fall
      in [noradrenaline] relative to the age-matched Wistar controls. CONCLUSIONS: The
      results indicate increased levels of NPY and noradrenaline in autonomic nerves,
      and of CGRP in sensory nerves, innervating the corpus cavernosum in Type I and in
      prediabetic Type II GK rats.

PMID- 19152795
TI  - Damage recognition by UV damage endonuclease from Schizosaccharomyces pombe.
AB  - UV damage endonuclease (UVDE) from Schizosaccharomyces pombe initiates repair of
      UV lesions and abasic sites by nicking the DNA 5' to the damaged site. In this
      paper we show that in addition UVDE incises DNA containing a single-strand nick
      or gap, but that the enzymatic activity on these substrates as well as on abasic
      sites strongly depends on the presence of a neighbouring pyrimidine residue. This
      indicates that, although UVDE may have been derived from an ancestral AP
      endonuclease its major substrate is a UV lesion and not an AP site. We propose
      that UVDE rotates two nucleotides into a pocket of the protein in order to bring
      the scissile bond close to the active site and that purine bases are excluded
      from this pocket. We also show that in the DNA complex residue Tyr-358 of UVDE
      penetrates the DNA helix causing unstacking of two residues opposite the lesion,
      thereby stabilizing the protein-DNA interaction, most likely by promoting bending
      of the DNA. In the absence of Tyr-358 the enzyme exhibits an increased catalytic
      activity on UV-induced lesions, but only at a lower pH of 6.5. At physiological
      conditions (pH 7.5) the mutant protein completely looses its catalytic activity
      although it can still bind to the DNA. We propose that in addition to stabilizing
      the bend in the DNA the hydrophobic side chain of Tyr-358 shields the active site
      from exposure to the solvent.

PMID- 19152796
TI  - The cryopreservation of high concentrated PBMC for dendritic cell (DC)-based
      cancer immunotherapy.
AB  - Peripheral blood mononuclear cells (PBMC) have been accepted as a unique material
      for cancer immunotherapy using dendritic cells (DC) or activated lymphocytes that
      are being developed as an alternative or adjuvant to conventional therapies such
      as surgery, chemotherapy and radiation treatment. Although successful
      cryopreservation of large numbers of PBMC is critical for the immunotherapy,
      subsequent functional study of the effects of PBMC cryopreservation on
      differentiation into immune cells has not been well defined. In this study, over
      1.0 x 10(8)cells/ml PBMC were cryopreserved as long as 52 weeks using a
      controlled-rate freezer (CRF) and stored in a vapor phase of liquid nitrogen
      tank. The effect of PBMC cryopreservation on differentiation into DC was studied
      by comparing the phenotypic and functional properties of immature DC (iDC) and
      mature DC (mDC) derived from cryopreserved PBMC to those from fresh PBMC. The
      results show that cryopreservation of PBMC at a fairly high cell concentration
      does not significantly affect cell recovery, viability, or phenotypes of PBMC.
      After differentiation into DC, iDC and mDC derived from cryopreserved PBMC had
      their typical phenotypes and function equivalent to those derived from fresh
      PBMC. Therefore, the improved cryopreservation process of PBMC described in this
      study is available for DC-based cancer immunotherapy.

PMID- 19152797
TI  - A functional interaction between Irx and Meis patterns the anterior hindbrain and
      activates krox20 expression in rhombomere 3.
AB  - Patterning of the vertebrate hindbrain involves a segmentation process leading to
      the formation of seven rhombomeres along the antero-posterior axis. While recent
      studies have shed light on the mechanisms underlying progressive subdivision of
      the posterior hindbrain into individual rhombomeres, the early events involved in
      anterior hindbrain patterning are still largely unknown. In this paper we
      demonstrate that two zebrafish Iroquois transcription factors, Irx7 and Irx1b,
      are required for the proper formation and specification of rhombomeres 1 to 4
      and, in particular, for krox20 activation in r3. We also show that Irx7
      functionally interacts with Meis factors to activate the expression of anterior
      hindbrain markers, such as hoxb1a, hoxa2 and krox20, ectopically in the anterior
      neural plate. Then, focusing on krox20 expression, we show that the effect of
      Irx7 and Meis1.1 is mediated by element C, a conserved cis-regulatory element
      involved in krox20 activation in the hindbrain. Together, our data point to an
      essential function of Iroquois transcription factors in krox20 activation and,
      more generally, in anterior hindbrain specification.

PMID- 19152798
TI  - Lateral-flow immunoassay for detecting drug-induced inhibition of mitochondrial
      DNA replication and mtDNA-encoded protein synthesis.
AB  - Drug-induced mitochondrial toxicity can occur as a result of inhibition of
      mitochondrial DNA (mtDNA) replication as with certain nucleoside reverse
      transcriptase inhibitors or inhibition of mtDNA-encoded protein synthesis as with
      certain antibacterials. Both types of dysfunction have the overall effect of
      reducing the level of proteins encoded by mtDNA. A lateral-flow immunoassay which
      measures the levels of both a mtDNA-encoded protein and a nuclear DNA-encoded
      protein allows simple and rapid determination of the ratio of these 2 proteins
      and, hence, identifies changes in mtDNA-encoded protein levels. Here, we describe
      an assay that compares the level of Complex IV (cytochrome c oxidase), a
      mitochondrial protein which has 3 subunits encoded by mtDNA and made by
      mitochondrial ribosomes, with that of frataxin, a protein encoded by nuclear DNA
      and made by cytosolic ribosomes. We tested a selection of antibacterials and
      antiretrovirals in cells and show that the ratio of Complex IV: frataxin
      decreases when a drug inhibits either mtDNA replication or mtDNA-encoded protein
      synthesis. The results obtained with the assay were confirmed by Western blotting
      and immunocytochemical analysis. The assay has high reproducibility, requires
      small amounts of sample, is quantitative, and is able to identify drugs which
      ultimately lead to a decrease in mtDNA-encoded proteins.

PMID- 19152799
TI  - Model for substrate interactions in C5a peptidase from Streptococcus pyogenes: A
      1.9 A crystal structure of the active form of ScpA.
AB  - The crystal structure of an active form of ScpA has been solved to 1.9 A
      resolution. ScpA is a multidomain cell-envelope subtilase from Streptococcus
      pyogenes that cleaves complement component C5a. The catalytic triad of ScpA is
      geometrically consistent with other subtilases, clearly demonstrating that the
      additional activation mechanism proposed for the Streptococcus agalactiae
      homologue (ScpB) is not required for ScpA. The ScpA structure revealed that
      access to the catalytic site is restricted by variable regions in the catalytic
      domain (vr7, vr9, and vr11) and by the presence of the inserted protease
      associated (PA) domain and the second fibronectin type III domains (Fn2).
      Modeling of the ScpA-C5a complex indicates that the substrate binds with carboxyl
      terminal residues (65-74) extended through the active site and core residues (1
      64) forming exosite-type interactions with the Fn2 domain. This is reminiscent of
      the two-site mechanism proposed for C5a binding to its receptor. In the nonprime
      region of the active site, interactions with the substrate backbone are predicted
      to be more similar to those observed in kexins, involving a single beta-strand in
      the peptidase. However, in contrast to kexins, there would be diminished emphasis
      on side-chain interactions, with little charged character in the S3-S1 and S6-S4
      subsites occupied by the side chains of residues in vr7 and vr9. Substrate
      binding is anticipated to be dominated by ionic interactions in two distinct
      regions of ScpA. On the prime side of the active site, salt bridges are predicted
      between P1', P2', and P7' residues, and residues in the catalytic and PA domains.
      Remote to the active site, a larger number of ionic interactions between residues
      in the C5a core and the Fn2 domain are observed in the model. Thus, both PA and
      Fn2 domains are expected to play significant roles in substrate recognition.

PMID- 19152800
TI  - In vivo treatment with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
      induces organ-specific alterations in in vitro repair of DNA
      pyridyloxobutylation.
AB  - To investigate the mechanisms responsible for inter-organ differences in
      susceptibility to 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK)-induced
      carcinogenesis, the objectives were to compare DNA repair activities of extracts
      from mouse lung and liver towards NNK-induced pyridyloxobutyl (POB) damage to
      plasmid DNA, and to determine if and the mechanism by which in vivo NNK treatment
      of mice alters DNA repair. Repair activity of POB adducts was three times greater
      in mouse liver than in mouse lung (P<0.05). Repair activities of lung extracts
      from mice 4 or 24 h post-NNK treatment were 30-45% those of control (P<0.05).
      Conversely, POB adduct repair was 2-3 times higher in liver extracts from NNK
      treated mice than in controls (4 h, 24 h, P<0.05). NNK treatment also decreased
      incision of POB adducts by 92% (4 h, P<0.05) in lung and increased incision by
      169% (24 h, P<0.05) in liver. NNK decreased immunoreactive levels of the incision
      protein RPA in lung (P<0.05) 4 h post-treatment but increased immunoreactive lung
      RPA and XPB after 24 h (P<0.05). In liver, levels of immunoreactive proteins,
      XPA, XPB and ERCC1 were increased after NNK treatment (24 h, P<0.05). Binding of
      XPA and XPB from liver extracts to POB adducts increased following NNK treatment,
      while binding of XPA and XPB from lung decreased (4 h, 24 h). These results
      suggest that lower incision activity of nucleotide excision repair and NNK
      mediated alterations in levels and activities of key incision proteins contribute
      to the relative susceptibility of mouse lung to NNK-induced carcinogenesis.

PMID- 19152801
TI  - Editorial comment on Nan, Y., Knosche, T. R., & Luo, Y.-J. (2006). Counting in
      everyday life: discrimination and enumeration. Neuropsychologia, 44, 1103-1113.

PMID- 19152802
TI  - The synthesis of 13alpha-androsta-5,16-diene derivatives with carboxylic acid,
      ester and carboxamido functionalities at position-17 via palladium-catalyzed
      carbonylation.
AB  - 17-Alkoxycarbonyl- and 17-carboxamido-3beta-hydroxy-13alpha-androsta-5,16-diene
      derivatives were synthetized in high yields in the palladium-catalyzed
      carbonylation reactions of the corresponding 3beta-hydroxy-17-iodo-13alpha
      androsta-5,16-diene. This substrate with a 17-iodo-16-ene functionality was
      obtained from the 17-keto derivative via its 17-hydrazone, which was treated with
      iodine in the presence of a base (1,1,3,3-tetramethylguanidine). 17-Carboxamides
      were obtained by chemoselective aminocarbonylation through the use of amines,
      including amino acid esters, as N-nucleophiles. The 17-methoxycarbonyl-16-ene
      derivative was synthetized by using methanol as O-nucleophile. The parent
      compound of this series, the 17-carboxylic acid derivative, was formed in the
      presence of water via hydroxycarbonylation.

PMID- 19152803
TI  - Steroidal saponins from Tribulus terrestris.
AB  - Five new steroidal saponins were isolated from the fruits of Tribulus terrestris.
      Their structures were fully established by spectroscopic and chemical analysis as
      (23S,25S)-5alpha-spirostane-24-one-3beta,23-diol-3-O-{alpha-l-rhamnopyranosyl-(1-
      >2)-O-[beta-d-glucopyranosyl-(1-->4)]-beta-d-galactopyranoside} (1), (24S,25S)
      5alpha-spirostane-3beta,24-diol-3-O-{alpha-l-rhamnopyranosyl-(1-->2)-O-[beta-d
      glucopyranosyl-(1-->4)]-beta-d-galactopyranoside} (2), 26-O-beta-d-glucopyranosyl
      (25R)-5alpha-furostan-2alpha,3beta,22alpha,26-tetraol-3-O-{beta-d-glucopyranosyl
      (1-->2)-O-beta-d-glucopyranosyl-(1-->4)-beta-d-galactopyranoside} (3), 26-O-beta
      d-glucopyranosyl-(25R)-5alpha-furostan-20(22)-en-2alpha,3beta,26-triol-3-O-{beta
      d-glucopyranosyl-(1-->2)-O-beta-d-glucopyranosyl-(1-->4)-beta-d
      galactopyranoside} (4), and 26-O-beta-d-glucopyranosyl-(25S)-5alpha-furostan-12
      one-22-methoxy-3beta,26-diol-3-O-{alpha-l-rhamnopyranosyl-(1-->2)-O-[beta-d
      glucopyranosyl-(1-->4)]-beta-d-galactopyranoside} (5). The isolated compounds
      were evaluated for cytostatic activity against HL-60 cells.

PMID- 19152804
TI  - Estrogen and progesterone interactive effects in postconfluent MCF-7 cell
      culture.
AB  - 17beta-Estradiol (E2) stimulates morphological differentiation of an MCF-7 human
      mammary carcinoma cell line resulting in the development of multicellular rounded
      nodules (foci) above the epithelial monolayer. Examining the combined effect of
      progesterone (P4) and E2 on foci formation we detected P4-dependent foci
      enlargement and phenotypic modification. Notably, P4 dose-dependently potentiated
      lower dose E2-induced increases in foci numbers. We detected P4-dependent changes
      in cytoskeleton protein expression levels and accelerated cell division. P4 alone
      or in combination with E2 additively modified the expression of adhesion proteins
      and stimulated expression of tropomyosin (Tm). Antiprogestin and antiestrogen
      pretreatment abrogated P4-dependent increases in foci number and stimulation of
      Tm expression, indicating involvement of both E2 and P4 receptor signaling. Novel
      aspects of endocrine-regulated changes in microfilament and adhesion protein
      composition are discussed in association with tumorigenesis and metastatic
      capability in breast carcinoma cells.

PMID- 19152805
TI  - Synergistic effect of polymorphisms of paraoxonase gene cluster and arsenic
      exposure on electrocardiogram abnormality.
AB  - Arsenic has been linked to increased prevalence of cancer and cardiovascular
      disease (CVD), but the long-term impact of arsenic exposure remains unclear.
      Human paraoxonase (PON1) is a high-density lipoprotein-associated antioxidant
      enzyme which hydrolyzes oxidized lipids and is thought to be protective against
      atherosclerosis, but evidence remains limited to case-control studies. Only
      recently have genes encoding enzymes responsible for arsenic metabolism, such as
      AS3MT and GSTO, been cloned and characterized. This study was designed to
      evaluate the synergistic interaction of genetic factors and arsenic exposure on
      electrocardiogram abnormality. A total of 216 residents from three tap water
      implemented villages of previous arseniasis-hyperendemic regions in Taiwan were
      prospectively followed for an average of 8 years. For each resident, a 12-lead
      conventional electrocardiogram (ECG) was recorded and coded by Minnesota Code
      standard criteria. Eight functional polymorphisms of PON1, PON2, AS3MT, GSTO1,
      and GSTO2 were examined for genetic susceptibility to ECG abnormality. Among 42
      incident cases with ECG deterioration identified among 121 baseline-normal
      subjects, arsenic exposure was significantly correlated with incidence of ECG
      abnormality. In addition, polymorphisms in two paraoxonase genes were also found
      associated with the incidence of ECG abnormality. A haplotype R-C-S constituted
      by polymorphisms of PON1 Q192R, -108C/T and PON2 C311S was linked to the
      increased risk. Subjects exposed to high levels of As (cumulative As exposure
      >14.7 ppm-year or drinking artesian well water >21 years) and carrying the R-C-S
      haplotype had significantly increased risks for ECG abnormality over those with
      only one risk factor. Results of this study showed a long-term arsenic effect on
      ECG abnormality and significant gene-gene and gene-environment interactions
      linked to the incidence of CVD. This finding might have important implications
      for a novel and potentially useful biomarker of arsenic risk.

PMID- 19152806
TI  - Continuous exposure to low concentrations of methylmercury impairs cerebellar
      granule cell migration in organotypic slice culture.
AB  - Chronic, low-level perinatal exposure to methylmercury (MeHg) is associated with
      neurological and motor deficits that appear to result from cerebellar
      dysfunction. Neuropathological studies suggest that these deficits are due to
      impaired cerebellar granule cell (CGC) migration. Although neuronal migration in
      vivo and in vitro has been shown to be impaired during acute and/or high level
      exposure to MeHg, the cellular effects of chronic exposure to submicromolar and
      micromolar levels of MeHg during development are not clear. The majority of CGC
      migration in rats occurs between postnatal days 8 and 14 (P8 and 14); migration
      peaks on P10 and 11. Organotypic cultures of parasagittal slices of cerebellum
      from P8 rats were exposed to low levels of MeHg (0.2-5.0microM) for 3 or 7 days,
      and CGC viability and migration were assessed. MeHg-induced cell death was time-
      and concentration-dependent. After 3 days of exposure CGC viability decreased in
      3microM MeHg and declined to 42.7% in 5microM MeHg. Cultures treated with MeHg
      for 7 days showed decreased CGC viability in 1microM MeHg, which declined to
      62.8% in 3microM MeHg. CGC migration was assessed by BrdU pulse-chase labeling.
      Migration into the internal granule cell layer (IGL) was impaired in cultures
      exposed to >or=1microM MeHg for 3 days or >or=0.5microM for 7 days. CGCs failed
      to initiate migration from the external germinal cell layer at the same level of
      exposure. For those cells which initiated migration, MeHg reduced the number that
      migrated into the IGL. This implied a slowing of migration once it had begun.
      These effects occurred with no overall change in cerebellar cortical structure,
      or loss of granule cell viability. Thus, chronic exposure to low micromolar
      concentrations of MeHg impairs development of the cerebellar cortex in a slice
      culture model.

PMID- 19152807
TI  - The Lantern: an ultra-light micro-drive for multi-tetrode recordings in mice and
      other small animals.
AB  - In vivo electrophysiological recordings from groups of distinguishable neurons in
      behaving mice is a technique with a rapidly growing appeal, particularly because
      it can be combined with gene targeting techniques. This methodology is deemed
      essential for achieving a flexible and versatile coupling of molecular-genetic
      manipulations with behavioral and system level analyses of the nervous system.
      One major obstacle in obtaining this technological integration is the relatively
      high weight and bulk size of the available implantable devices for ensemble
      recordings as compared to the size of the animal. This imposes considerable
      physical stress on the animals and may prevent them from performing complex
      behavioral tasks for more than a few minutes. We developed a novel micro-drive
      which allows independent day-to-day positioning of up to 6 tetrodes in the mouse
      brain, with an extremely reduced weight and size. The system is based on an
      "exoskeleton" as its structural element, and allows a completely rectilinear path
      of the electrodes inside the drive and into the brain. Tests showed that mice can
      tolerate the chronically implanted device very well up to 12 weeks after
      implantation, while exhibiting normal behavior. Cell yields and stability
      obtained with this drive in two different brain areas (the hippocampus and
      orbitofrontal cortex) were comparable to those of traditional recording systems,
      usually applied to rats. The device may greatly expand possibilities to combine
      gene targeting and ensemble recording techniques, in behaviorally varied as well
      as cognitively demanding settings.

PMID- 19152808
TI  - Purification of anatid herpesvirus 1 particles by tangential-flow ultrafiltration
      and sucrose gradient ultracentrifugation.
AB  - Anatid herpesvirus 1 (AHV-1) infection causes substantial economic losses to the
      world-wide waterfowl production. However, little is known about the efficient
      method used to study the purification of AHV-1 and the negative staining
      morphology of the purified virus particles. This lack of knowledge is one of the
      important factors that have affected the progress of research studies on AHV-1
      molecular virology to such an extent that they are lagging far behind those on
      other members of the same family Herpesviridae. Therefore, an efficient method
      for purifying AHV-1 from cell-culture medium has been developed. Abundant AHV-1
      particles, whose morphological features match those of herpesvirus, were obtained
      by using the following procedures: (1) conventional differential centrifugation
      for removal of debris after cell disruption, (2) tangential-flow ultrafiltration
      coupled with sucrose density gradient ultracentrifugation for isolation of the
      virus, and (3) conventional differential ultracentrifugation for virus
      concentration. The purified AHV-1 particles were subjected to transmission
      electron microscopy (TEM), infectivity and recovery tests, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting assay, and agar gel
      diffusion test (AGDT). The results of examinations revealed that purified AHV-1
      particles were free of visible contamination or degradation. The purified AHV-1
      particles were biologically active and were successful in initiating infection
      upon inoculation into susceptible duck embryo fibroblast. The procedures are
      reliable technically and feasible for purification of large volumes of viruses.

PMID- 19152809
TI  - Rapid identification of viruses causing sugarcane mosaic by direct sequencing of
      RT-PCR products from crude extracts: a method for large scale virus surveys.
AB  - Sugarcane mosaic virus (SCMV) and sorghum mosaic virus (SrMV) diversity studies
      are important to characterize virus populations in sugarcane producing areas,
      enabling (i) identification of shifts in predominant strains, (ii) detecting
      associations of strains with specific varieties, and (iii) possibly exposing the
      appearance of new strains which may affect the performance of varieties in a
      region. Recent studies have shown significant sequence variability within SCMV
      populations around the world, indicating that isolate identification would be
      best achieved by direct analysis of sequence data. Because virus sequence-based
      studies that require the characterization of large numbers of isolates may be
      impractical using standard sample preparation and processing methodology, a
      simple protocol that yields quality sequence information, requiring neither viral
      RNA purification nor cloning of RT-PCR products was developed. Rapid virus
      release extracts are obtained by submerging a portion of leaf tissue into an
      extraction buffer, followed by a brief incubation at 95 degrees C. An aliquot of
      the extract is pipetted into an RT-PCR amplification mix for the detection of
      SCMV and the SrMV coat protein gene fragments. RT-PCR fragments are sequenced
      directly using oligonucleotide primers similar to the RT-PCR primers, yielding
      sequence information of an adequate quality. This rapid, cost effective protocol
      is practical for large scale virus diversity and evolutionary studies.

PMID- 19152810
TI  - Neutralizing monoclonal antibodies to different clades of Influenza A H5N1
      viruses.
AB  - Four IgG(1kappa) monoclonal antibodies (mAbs) against Influenza
      A/Chicken/Vietnam/8/2004 (H5N1) virus are described. Three of these showed
      neutralizing activities against H5N1 strains from clades 1, 2 and 3 using a
      retroviral pseudotype or live virus microneutralization assay. In the pseudotype
      assay, the IC(90) neutralizing titre range was >1600-51,200, and with the
      microneutralization was 80> or =10,240. MAb 1C1 showed strong neutralizing
      activities in both assays. All four mAbs reacted specifically to the immunogen by
      immunohistochemical staining and to A/Hong Kong/483/1997 (H5N1) and
      A/Thailand/1(KAN-1)/2004 (H5N1)-infected MDCK cells by immunofluorescence. ELISA
      titrations of the mAbs showed specificity for H5N1 haemagglutinin (HA) and no
      cross-reactivity to 15 other Influenza A subtypes. Only mAbs 1C1 and the non
      neutralizing 1F7 reacted with HA(1), the cleaved subunit of HA, by Western blot.
      These results suggest that the mAbs recognize distinct or overlapping epitopes
      and will be useful reagents for construction of specific rapid point-of-care
      assays or for therapeutic use.

PMID- 19152812
TI  - Autophagy in the cardiovascular system.
AB  - Autophagy is a catabolic pathway for bulk turnover of long-lived proteins and
      organelles via lysosomal degradation. Growing evidence reveals that autophagy is
      involved in the progression or prevention of many human diseases. Here we discuss
      the role of autophagy in the normal heart, in heart disease and atherosclerosis.
      In the heart, autophagy functions predominantly as a pro-survival pathway during
      cellular stress by removing protein aggregates and damaged organelles, protecting
      the heart against famine, excessive beta-adrenergic stimulation and ischemia.
      However, when severely triggered, e.g. during reperfusion, the autophagic
      machinery may lead to cell death. Furthermore, autophagy modulates cardiac
      hypertrophy and the transition from hypertrophy to heart failure. During aging,
      lipofuscin is formed via autophagy in the heart and impairs autophagy. Basal
      autophagy in atherosclerotic plaques is a survival mechanism safeguarding plaque
      cells against cellular distress, in particular oxidative injury, metabolic stress
      and inflammation, by removing harmful oxidatively modified proteins and damaged
      components. Hence, autophagy is anti-apoptotic and contributes to cellular
      recovery in an adverse environment. However, excessively stimulated autophagy
      causes autophagic death in plaque cells and is detrimental. Ceroid that is formed
      via autophagy in atherosclerotic arteries impairs autophagy and induces
      apoptosis. Basal autophagy can be intensified by appropriate drugs and
      pharmacological approaches have been developed to stabilize rupture-prone plaques
      through selective induction of macrophage autophagic death, without affecting the
      plaque stabilizing smooth muscle cells.

PMID- 19152811
TI  - D-cycloserine accelerates the extinction of cocaine-induced conditioned place
      preference in C57bL/c mice.
AB  - Recently, it was shown that D-cycloserine (DCS, a NMDA partial agonist)
      facilitated extinction of fear as well as cocaine conditioned place preference
      (CPP) in rats. METHODS: The present study examined the effects of DCS (15 mg/kg
      i.p. and 30 mg/kg i.p.) on extinction and renewal of cocaine-induced CPP in
      C57bL/c mice. In parallel, we examined the effects of DCS on locomotor activity.
      RESULTS: Extinction to cocaine CPP was significantly faster with DCS than with
      vehicle treatment (three versus six sessions, respectively). After extinction was
      achieved, mice were retested for CPP 1 and 2 weeks later. All animals maintained
      extinction to CPP 1 week later, but at 2 weeks, the vehicle and the 15 mg/kg DCS
      treated animals maintained the extinction, but the 30 mg/kg DCS-treated mice had
      renewed CPP. During induction of cocaine CPP, mice displayed enhanced locomotor
      activity following treatment with cocaine, as expected, based on previous
      literature. During extinction, there were no differences in locomotor activity
      between the vehicle and the 15 mg/kg DCS-treated mice, whereas the 30 mg/kg DCS
      treated animal showed significant locomotor activity inhibition. These results
      corroborate in mice the previously reported acceleration of extinction to cocaine
      induced CPP by DCS in rats. However, we also show that the higher DCS doses
      facilitated CPP reestablishment after extinction. Thus, while DCS could be
      beneficial in accelerating the extinction to conditioned responses in addiction
      it could, at higher doses, increase the risk of relapse. Thus, studies evaluating
      the beneficial therapeutic effects of DCS should assess not only the short-term
      effects but also the potential of longer lasting undesirable effects.

PMID- 19152813
TI  - Emergence of new strains of Watermelon mosaic virus in South-eastern France:
      evidence for limited spread but rapid local population shift.
AB  - Severe symptoms caused by Watermelon mosaic virus (WMV) in zucchini squash leaves
      and fruits have been observed since 1999 in South-eastern (SE) France. Their
      appearance correlates with the introduction of new, "emerging" (EM) isolates
      distant at the molecular level from the "classic" (CL) isolates present for more
      than 30 years. To understand the origin and spread of EM isolates, a survey was
      performed between 2004 and 2007. WMV isolates collected were characterized by
      sequencing part of the polymerase and coat protein coding regions. This revealed
      the presence of EM isolates in SE France only, whereas CL isolates were
      widespread throughout the country. Besides, four subgroups of EM isolates were
      observed in SE France, suggesting multiple introductions. Recombinants between CL
      and EM groups, which probably arose locally, were observed during the survey. A
      strong geographic structure that remained stable during the 4 years was observed
      between different EM isolates. Our results showed that EM isolates did not spread
      over long distances, but rapidly replaced the pre-existing CL isolates in all
      sites where both groups occurred.

PMID- 19152814
TI  - Seed, soil and vegetative transmission contribute to the spread of pecluviruses
      in Western Africa and the Indian sub-continent.
AB  - Peanut clump and sugarcane red leaf mottle diseases are caused by viruses of the
      genus Pecluvirus. Indian peanut clump virus occurs in the Indian sub-continent
      and Peanut clump virus in West Africa. A feature of these viruses is that they
      are both seed and soil transmitted. Both modes of transmission contribute to long
      term persistence and field spread. Data on seed transmission in pearl millet,
      virus movement within the plant and virus diversity based on RNA-1 partial
      sequences are presented. This study emphasizes that pecluviruses are also viruses
      of cereals infecting sorghum and pearl millet, and highlights a correlation
      between the countries cultivating these two crops and the virus distribution.
      Ways of controlling pecluviruses and their vector, Polymyxa graminis, taking into
      account the virus dissemination routes, are proposed.

PMID- 19152815
TI  - Molecular epidemiology of Zucchini yellow mosaic virus in France: an historical
      overview.
AB  - Cucurbit viruses are involved in complex and changing pathosystems in France,
      with new virus strains or species regularly reported. Zucchini yellow mosaic
      virus (ZYMV) is an archetypal emerging virus that was reported in France in 1979.
      It has since caused sporadic but occasionally very severe economic losses and its
      epidemiology still remains poorly understood. Partial sequencing of the viral
      genome has been used to characterize ZYMV isolates that occurred over a 29-year
      period in experimental plots at Montfavet, France (n=227), or that were received
      through a national survey for cucurbit viruses conducted in France from 2004 to
      2007 (n=198). A total of 34 haplotypes were differentiated belonging to five
      molecular groups, three including isolates already described in France and two
      corresponding to isolates that emerged in France within the last 5 years.
      Comparison of haplotypes found at one location during successive years revealed
      contrasting situations. When they were either the same or closely related
      haplotypes, this suggested the availability of overwintering hosts, whereas when
      they belonged to different molecular groups this indicated shifts in viral
      populations with possible new introductions. The contribution of molecular
      epidemiology in tracing the origin of ZYMV in the French West Indies is also
      reviewed.

PMID- 19152816
TI  - The role of plant biosecurity in preventing and controlling emerging plant virus
      disease epidemics.
AB  - A number of research strategies have been initiated over the last decade to
      enhance plant biosecurity capacity at the pre-border, border and post-border
      frontiers. In preparation for emerging plant virus epidemics, diagnostic manuals
      for economically important plant viruses that threaten local industries have been
      developed and validated under local conditions. Contingency plans have also been
      prepared that provide guidelines to stakeholders on diagnostics, surveillance,
      survey strategies, epidemiology and pest risk analysis. Reference collections
      containing validated positive virus controls have been expanded to support a wide
      range of biosecurity sciences. Research has been conducted to introduce high
      throughput diagnostic capabilities and the design and development of advanced
      molecular techniques to detect virus genera. These diagnostic tools can be used
      by post entry quarantine agencies to detect known and unknown plant viral agents.
      Pre-emptive breeding strategies have also been initiated to protect plant
      industries if and when key exotic viruses become established in localized areas.
      With the emergence of free trade agreements between trading partners there is a
      requirement for quality assurance measures for pathogens, including viruses,
      which may occur in both the exporting and importing countries. These measures are
      required to ensure market access for the exporting country and also to minimize
      the risk of the establishment of a damaging virus epidemic in the importing
      country.

PMID- 19152817
TI  - Newcastle disease virus-induced cytopathic effect in infected cells is caused by
      apoptosis.
AB  - The velogenic Newcastle disease virus (NDV) causes highly infectious and
      economically significant Newcastle disease (ND) in birds of various species. In
      cell culture NDV induces cytopathic effect (CPE) characterized by rounding,
      vacuolation, syncytia formation and cell death. Aside from cell to cell fusion
      caused by the F and HN glycoprotein of the virus molecular events leading to cell
      death are not known. In the current study, NDV-infected Vero cells, at 48 h p.i.,
      showed nuclear condensation, cytoplasm blebbing, DNA fragmentation, and
      phosphatidylserine translocation to the cell surface. In addition, virus-infected
      cells demonstrated decreased DNA content and an increased Bax to Bcl-2 ratio, p53
      level and caspase 3, 8, 9 expression compared to mock-infected cells. Based on
      these results, it was concluded that CPE in NDV-infected cells was caused by to
      the induction of apoptosis with the involvement of p53 and the Bax, dependent
      apoptotic pathways.

PMID- 19152818
TI  - Newer insecticides for plant virus disease management.
AB  - Effective management of insect and mite vectors of plant pathogens is of crucial
      importance to minimize vector-borne diseases in crops. Pesticides play an
      important role in managing vector populations by reducing the number of
      individuals that can acquire and transmit a virus, thereby potentially lowering
      disease incidence. Certain insecticides exhibit properties other than lethal
      toxicity that affect feeding behaviours or otherwise interfere with virus
      transmission. To evaluate the potential of various treatments against the Bemisia
      tabaci-transmitted Cucurbit yellow stunting disorder virus (CYSDV), insecticide
      field trials were conducted in Yuma, AZ, USA, during spring and autumn growing
      seasons. Differences in vector-intensity each season led to mixed results, but at
      least five insecticide treatments showed promise in limiting virus spread during
      spring 2008. Increasing concern among growers in this region regarding recent
      epidemics of CYSDV is leading to more intensive use of insecticides that
      threatens to erupt into unmanageable resistance. Sustainability of insecticides
      is an important goal of pest management and more specifically resistance
      management, especially for some of the most notorious vector species such as B.
      tabaci and Myzus persiscae that are likely to develop resistance.

PMID- 19152819
TI  - Behavioural aspects influencing plant virus transmission by homopteran insects.
AB  - Homopterans including aphids, whiteflies and leafhoppers are the major vectors of
      viruses comprising more than 80% of insect-transmitted viruses which represents
      close to 400 virus species within 39 different genera. Host plant recognition by
      homopterans requires a series of steps that are linked to plant virus
      transmission, including host searching or pre-alighting behaviour, probing on
      superficial tissues, settlement and stylet penetration to the target feeding
      tissues and salivation and continuous sap ingestion from the preferred feeding
      site. This review considers how vector behaviour influences the transmission and
      spread of plant viruses depending on the type of virus-vector relationship. Most
      studies have concentrated on aphid-transmitted viruses and particular probing and
      feeding behavioural processes and activities leading to the transmission of
      cuticula-borne and circulative viruses have been identified. The review also
      focuses on which are the most likely retention sites within the insect's body of
      cuticula-borne viruses. Finally, the influences of virus infection on vector
      behaviour such as changes in the attractiveness, settlement or feeding preference
      together with changes on vector performance (development, fecundity, rate of
      population increase and survival) are discussed.

PMID- 19152820
TI  - Epidemiology and integrated management of persistently transmitted aphid-borne
      viruses of legume and cereal crops in West Asia and North Africa.
AB  - Cool-season food legumes (faba bean, lentil, chickpea and pea) and cereals (bread
      and durum wheat and barley) are the most important and widely cultivated crops in
      West Asia and North Africa (WANA), where they are the main source of
      carbohydrates and protein for the majority of the population. Persistently
      transmitted aphid-borne viruses pose a significant limitation to legume and
      cereal production worldwide. Surveys conducted in many countries in WANA during
      the last three decades established that the most important of these viruses are:
      Faba bean necrotic yellows virus (FBNYV: genus Nanovirus; family Nanoviridae),
      Bean leafroll virus (BLRV: genus Luteovirus; family Luteoviridae), Beet western
      yellows virus (BWYV: genus Polerovirus; family Luteoviridae), Soybean dwarf virus
      (SbDV: genus Luteovirus; family Luteoviridae) and Chickpea chlorotic stunt virus
      (CpCSV: genus Polerovirus; family Luteoviridae) which affect legume crops, and
      Barley yellow dwarf virus-PAV (BYDV-PAV: genus Luteovirus; family Luteoviridae),
      Barley yellow dwarf virus-MAV (BYDV-MAV: genus Luteovirus; family Luteoviridae)
      and Cereal yellow dwarf virus-RPV (CYDV-RPV: genus Polerovirus; family
      Luteoviridae) which affect cereal crops. Loss in yield caused by these viruses is
      usually high when infection occurs early in the growing season. Many aphid vector
      species for the above-mentioned viruses are reported to be prevalent in the WANA
      region. In addition, in this region many wild species (annual or perennial) were
      found infected with these viruses and may play an important role in their ecology
      and spread. Fast spread of these diseases was always associated with high aphid
      vector populations and activity. Although virus disease management can be
      achieved by combining several control measures, development of resistant
      genotypes is undoubtedly one of the most appropriate control methods. Over the
      last three decades barley and wheat genotypes resistant to BYDV, faba bean
      genotypes resistant to BLRV, and lentil genotypes resistant to BLRV, FBNYV and
      SbDV have been successfully identified. Moreover, progress has been made in
      disease management of some of these viruses using a combination of management
      options. Experience gathered over the last few decades clearly showed that no
      single method of virus disease control suffices to reduce yield losses in legume
      and cereal crops.

PMID- 19152821
TI  - Non-cultivated plants of the Tallgrass Prairie Preserve of northeastern Oklahoma
      frequently contain virus-like sequences in particulate fractions.
AB  - The diversity of viruses associated with non-cultivated plants was assessed from
      plant samples collected in the Tallgrass Prairie Preserve of northeastern
      Oklahoma, USA. The samples were processed to determine the sequences of nucleic
      acids extracted from the virus-like particle fraction of plant homogenates.
      Sequences from 95 specimens of 52 plant species included those of probable origin
      from the genomes of plants (including retroelements), bacteria, fungi, other
      organisms, and viruses. Virus-like sequences were identified in sequences from
      25% of the specimens, coming from 19% of the plant species. Evidence of a member
      of the genus Tymovirus was found in 16 specimens of 6 plant species, making it
      the most predominant virus associated with the sampled plants. There was evidence
      of the presence of more than one virus in each of six specimens.

PMID- 19152822
TI  - Differences in food supplies of U.S. households with and without overweight
      individuals.
AB  - Household food supplies of families with at least one child 12 years or younger
      (n=100) were inventoried in order to describe its nutrient content and compare
      food supplies of families with and without overweight individuals (i.e., healthy
      vs. overweight mothers; healthy vs. overweight fathers; healthy vs. overweight
      child[ren]). Nutrient adequacy ratios (NAR) for carbohydrate, dietary fiber,
      calcium, iron, total fat, and saturated fat were approximately one indicating
      amounts available per 2000 calories approximately equaled the Daily Value. NARs
      for protein, sugar, vitamin A, vitamin C, and sodium exceeded one and cholesterol
      NAR was less than one. Households were similar in number of household members,
      days until they planned to grocery shop again, and total days of meals and snacks
      to be served from household food supplies until the next grocery shopping trip.
      Frozen vegetables contributed significantly greater amounts of calories,
      carbohydrates, fat, and protein and meat supplied significantly more fat and
      protein in households with overweight fathers than in households with healthy
      weight fathers. In households with an overweight child, grains supplied
      significantly more protein and carbohydrate than in comparison households.
      Encouraging healthful changes to the home food supply may result in improvements
      in dietary intake and overall weight status.

PMID- 19152823
TI  - Low serum BDNF and food intake regulation: a possible new explanation of the
      pathophysiology of eating disorders.
AB  - BACKGROUND: Several lines of evidence suggest that brain-derived neurotrophic
      factor (BDNF) plays an important role in weight regulation and eating behavior,
      and poorly balanced diets lead to a decrease in blood BDNF levels. However,
      studies regarding BDNF blood levels in eating disorders (ED) have yielded
      inconsistent results. We measured serum concentrations of BDNF and assessed
      behavior and cognition related to eating in ED patients and control subjects.
      METHODS: Forty female drug-free patients [19 with anorexia nervosa (AN), 21 with
      bulimia nervosa (BN)], who did not meet the diagnostic criteria for depressive
      disorder, and 24 age-matched normal control subjects were enrolled in the current
      study. We evaluated eating-related psychopathology and depressive symptoms using
      the Eating Disorder Inventory-2 (EDI-2), Eating Attitude Test-26 (EAT-26) and the
      Hamilton Depression Rating Scale (HDRS), and measured serum BDNF levels by an
      enzyme-linked immunosorbent assay. RESULTS: Compared to normal controls, serum
      levels of BDNF were significantly reduced in AN, but not in BN. There was a
      significant positive correlation between serum BDNF levels and BMI in both AN
      patients (r=.649, p=.003) and BN patients (r=.626, p=.002). However, no
      correlation between serum BDNF levels and BMI was detected in the controls.
      Furthermore, there was a significant negative correlation between serum BDNF
      levels and the oral control subscale scores of EAT in both AN patients (r=-.506,
      p=.027) and BN patients (r=-.511, p=.018); whereas, no correlation was detected
      in normal controls. CONCLUSION: Our study demonstrated that individuals showing
      more extreme food intake regulation were those with lower serum BDNF levels. This
      finding is contrary to that in mice where mice with reduced BDNF levels showed
      aberrant eating behavior. This result suggests that BDNF is no longer functioning
      appropriately in ED patients, which could be an important factor in the
      pathophysiological of ED.

PMID- 19152824
TI  - The antigenotoxic activities of cactus (Opuntia ficus-indica) cladodes against
      the mycotoxin zearalenone in Balb/c mice: prevention of micronuclei, chromosome
      aberrations and DNA fragmentation.
AB  - Zearalenone (ZEN) is a potent estrogenic metabolite. Evidence of its cytotoxicity
      and genotoxicity has recently emerged from several reports. This study was
      conducted to evaluate the ability of cactus (Opuntia ficus-indica) cladodes to
      protect Balb/c mice against ZEN induced genotoxicity. To this end, the effect of
      a single dose of ZEN (40 mg/kg b.w.) alone and with extract of cactus cladodes
      (25, 50 and 100 mg/kg b.w.) was monitored by measuring: (i) micronuclei induction
      in bone marrow cells, (ii) chromosome aberrations mainly breaks and gaps in bone
      marrow cells also and finally and (iii) DNA fragmentation in liver and kidney.
      Our results clearly show that ZEN is genotoxic to Balb/c mice. It induces DNA
      damage as indicated by DNA fragmentation, micronuclei and chromosomal aberrations
      in bone marrow cells. It is of note that cactus cladodes extract assayed alone at
      high dose (100 mg/kg b.w.) was found completely safe and did not induce any
      genotoxic effects. The simultaneous administration of cactus cladodes extract
      with ZEN resulted in an efficient prevention of micronuclei (the number of PCE MN
      decreased from 71.3+/-6.1 for animals treated with Zen to 32.6+/-15.5 for animals
      treated with cactus cladodes), chromosomal aberrations frequency (the % of
      chromosomal aberrations decreased from 38.3+/-3.0 to 18.6+/-1.1) in bone marrow
      cells and of DNA fragmentation compared to the group treated with ZEN alone. It
      could be concluded that cactus cladodes extract was effective in the protection
      against ZEN genotoxicity. This could be relevant, particularly with the emergent
      demand for natural products which may neutralize the genotoxic effects of the
      multiple food contaminants.

PMID- 19152825
TI  - Methoxy VO-salen complex: in vitro antioxidant activity, cytotoxicity evaluation
      and protective effect on CCl4-induced oxidative stress in rats.
AB  - Reactive oxygen species (ROS) play crucial roles in normal physiological
      processes. However, the overproduction of ROS is involved in the onset of many
      degenerative diseases. Regarding this fact, discovery of new antioxidants is
      interesting for many research groups. In this study, we evaluated the antioxidant
      properties of a methoxy VO-salen (MetVO-salen) complex employing various in vitro
      systems. In addition, the cytotoxic effect of MetVO-salen was assessed based on
      MTT in treated K562 cells. In an in vivo approach, the protective effect of MetVO
      salen against CCl(4)-induced oxidative stress in rats was also investigated in
      terms of superoxide dismutase (SOD) and catalase (CAT) activities, as well as in
      terms of the levels of malondialdehyde (MDA) and glutathione (GSH). Our results
      indicated that MetVO-salen has an effective capability in scavenging superoxide
      (O*2-) and hydrogen peroxide (H(2)O(2)) radicals in a dose-dependent manner. In
      vivo results also showed that the administration of MetVO-salen to the CCl(4)
      treated rats caused a significant (222%) increase in SOD activity, a 59%
      enhancement in GSH content and a 31% decrease in the level of MDA compared to the
      CCl(4)-treated control rats. Overall, MetVO-salen appears to be an effective
      antioxidant and is quite suitable for further biological evaluation.

PMID- 19152826
TI  - A simple pre-treatment of aluminium cookware to minimize aluminium transfer to
      food.
AB  - In this work, we studied aluminium leaching from cookware to food under the
      effect of citric acid that is commonly found in foods and beverages. The authors
      showed that boiling the cookware in water prior to cooking is suitable for the
      decrease of aluminium leaching into food by a factor up to sixty (with a
      corresponding decrease of the aluminium intake by consumers). The effect of the
      pre-treatment has been studied by scanning electron microscopy and X-Ray
      diffraction and the effect has been attributed to changes in the structure and
      morphology of the passivation layer, from an initial heterogeneous layer to a
      surface uniformly covered with fine needles of Boehmite (alpha-AlOOH).

PMID- 19152827
TI  - Sildenafil attenuates renal injury in an experimental model of rat cisplatin
      induced nephrotoxicity.
AB  - Sildenafil is the first commercially available selective inhibitor of
      phosphodiesterase-5 (PDE5) and is widely used for the treatment of erectile
      dysfunction. In recent years, investigations of the role of sildenafil in
      cardioprotection in animal models have received considerable interest. We
      evaluated whether sildenafil can attenuate cisplatin-induced nephrotoxicity in a
      rat experimental model. Male Sprague-Dawley rats were divided into five groups:
      control rats, sildenafil-control rats, cisplatin-injected rats (5 mg kg(-1) IP,
      single dose), sildenafil-treated cisplatin-injected rats (0.4 mg kg(-1), daily),
      and sildenafil+NG-nitro-l-arginine methyl ester hydrochloride (l-NAME)-treated
      rats. The molecular, functional, and structural parameters of the kidney were
      measured. At 96 h after cisplatin injection, serum levels of creatinine were
      lower in rats treated with both sildenafil+cisplatin compared with rats treated
      with cisplatin alone, and renal iNOS and eNOS expression was significantly higher
      in sildenafil+cisplatin-treated rats compared with rats treated with cisplatin
      alone (all P<0.05). Renal Bax gene and protein expression was significantly
      higher in cisplatin-treated rats compared with control rats, and sildenafil
      treatment significantly reduced the levels of Bax and increased the renal Bax/Bcl
      2 ratio (P<0.05). Sildenafil treatment also reduced renal caspase-3 activation
      and TUNEL-positive apoptotic cells. These data suggest that sildenafil attenuates
      experimental cisplatin-induced nephrotoxicity by preventing apoptosis.

PMID- 19152828
TI  - New insights into the human body iron metabolism analyzed by a Petri net based
      approach.
AB  - Iron homeostasis is one of the most important biochemical processes in the human
      body. Despite this fact, the process is not fully understood and until recently
      only rough descriptions of parts of the process could be found in the literature.
      Here, an extension of the recently published formal model of the main part of the
      process is presented. This extension consists in including all known mechanisms
      of hepcidin regulation. Hepcidin is a hormone synthesized in the liver which is
      mainly responsible for an inhibition of iron absorption in the small intestine
      during an inflammatory process. The model is expressed in the language of Petri
      net theory which allows for its relatively easy analysis and simulation.

PMID- 19152829
TI  - Factors involved in inflammation-induced developmental white matter damage.
AB  - Developmental white matter damage is a brain pathology associated with several
      long-term neurological disorders. An inflammatory insult has been suggested as
      the major instigating event. This study investigated the relative influence of
      inflammation, blood-brain barrier permeability and glial ontogeny in white matter
      damage. Systemic inflammation was induced in Monodelphis domestica (opossum) by
      serial intraperitoneal injections of lipopolysaccharide at different stages of
      brain development. Volume of white matter was estimated for the external capsule.
      Blood-brain barrier permeability was assessed immunocytochemically. Quantitative
      RT-PCR was used to measure relative levels of mRNA for IL-1beta, IL-6 and COX-2.
      Developmental changes in numbers and appearance of microglia and astrocytes were
      estimated. Results showed that in response to systemic inflammation, white matter
      was reduced in the external capsule during a circumscribed period only. At the
      same developmental stage blood-brain barrier permeability was altered, cerebral
      inflammatory response was present and numbers of microglia increased. However,
      the periods of altered blood-brain barrier permeability and the cerebral
      inflammatory response were longer than the period of the external capsule's
      susceptibility to white matter damage, which coincided with the developmental
      increase in the number of astrocytes in this tract. Thus, the mechanism of white
      matter damage following systemic inflammation is multifactorial, including
      cerebral inflammation and breakdown of brain barriers occurring simultaneously at
      specific stages of glial cell development.

PMID- 19152830
TI  - Modifying effects of prepubertal exposure to potassium perchlorate and
      tetrabromobisphenol A on susceptibility to N-bis(2-hydroxypropyl)nitrosamine- and
      7,12-dimethylbenz(a)anthracene-induced carcinogenesis in rats.
AB  - Early life exposure to certain kinds of chemicals is of concern because of a
      possible increase in cancer risk, but relevant data are limited. In the present
      experiment, modifying effects of prepubertal administration of potassium
      perchlorate (KClO(4)) and tetrabromobisphenol A (TBBPA) on susceptibility to
      multi-organ carcinogenesis were evaluated. F344 dam rats were administered 0%
      (control), 0.01%, 0.1% or 1% TBBPA in diet or 0.01% KClO(4) in drinking water
      after parturition. Their weaned offspring in each group were treated for 2 weeks
      in the same manner. From 6 weeks of age, all offspring were treated with N-bis(2
      hydroxypropyl)nitrosamine in drinking water for 4 weeks. In addition the females
      at 7 weeks of age were gavaged once with 7,12-dimethylbenz(a)anthracene. At weeks
      39 and 47 of age, the males and females, respectively, were euthanized and the
      liver, kidney, lung, esophagus, thyroid, urinary bladder, testis, epididymis,
      ovary and mammary gland were histopathologically examined. The incidences of
      thyroid follicular adenomas in 1% TBBPA females (p<0.05) and of transitional cell
      papillomas in the urinary bladder of 0.01%, 0.1% and 1% TBBPA females were
      increased (p<0.05) as compared to the controls. These results indicate that
      prepubertal exposure to TBBPA raises susceptibility to thyroid and urinary
      bladder tumorigenesis in rats. Although causes of the effect on thyroid
      carcinogenesis might be direct and/or indirect hormonal actions, further studies
      are needed for confirmation.

PMID- 19152831
TI  - Steroidogenesis-disrupting compounds can be effectively studied for major
      fertility-related endpoints using in vitro cultured mouse follicles.
AB  - Biologically relevant bioassays are needed to test various endocrine disrupters
      (EDs). A mouse follicle culture model could allow measuring steroidogenic enzyme
      function in combination with oocyte growth and meiotic maturation using routine
      methodology. Three steroidogenesis-disrupting 'model' chemicals were tested;
      vorozole (VOR), aminoglutethimide (AMG), and ketoconazole (KCZ). Along with
      visual assessment of follicular growth, differentiation and oocyte growth and
      maturation by conventional light microscopy, steroid secretion measurements
      allowed to confirm literature findings from in vivo animal studies and more
      complex in vitro tests. The bioassay was applied for a dose-response study of
      mono(2-ethylhexyl)phthalate (MEHP), a chemical known to disrupt several
      steroidogenic enzymes. This bioassay was able to confirm an increased
      inactivation of E(2) to E(1) and an induced precocious progesterone increase,
      implying that MEHP can disrupt follicle differentiation and impact the
      reproductive axis. This in vitro ovarian model allows to reduce animal use by
      performing synchronous culture of large numbers of early preantral ovarian mouse
      follicles and is informative on multiple fertility-related endpoints.

PMID- 19152832
TI  - Dermal microdialysis of inflammatory markers induced by aliphatic hydrocarbons in
      rats.
AB  - In the present study we made an attempt to understand the skin irritation cascade
      of selected aliphatic hydrocarbons using microdialysis technique. Microdialysis
      probes were inserted into dermis in the dorsal skin of hairless rats. After 2h of
      probes insertion, occlusive dermal exposure (2h) was carried out with 230 microl
      of nonane, dodecane and tetradecane, using Hill top chambers((R)). Inflammatory
      biomarkers such as substance P (SP), alpha-melanocyte stimulating hormone (alpha
      MSH) Interleukin 6 (IL-6) and prostaglandin E2 (PGE(2)) were analyzed in the
      dialysis samples by enzyme immunoassay (EIA). SP, alpha-MSH and IL6 were released
      in significant amounts following the dermal exposure of nonane and dodecane,
      whereas tetradecane did not induce any of these markers in significant amounts
      compared to control. Nonane increased the PGE(2) levels in significant amounts
      within 2h of chemical exposure compared to dodecane and tetradecane. IL-6
      response was found to be slow and 2-3-fold increase in IL-6 levels was observed
      after 5h following nonane and dodecane application. The magnitude of skin
      irritation exerted by all three chemicals was in the order of
      nonane>or=dodecane>or=tetradecane. The results demonstrate that microdialysis can
      be used to measure the inflammatory biomarkers in the skin irritation studies and
      irritation response of chemicals was quantifiable by this method. In conclusion,
      microdialysis was found to be an excellent tool to measure several inflammatory
      biomarkers as a function of time after dermal exposures with irritant chemicals.

PMID- 19152833
TI  - Central inhibition of interleukin-1beta ameliorates sickness behavior in aged
      mice.
AB  - In elderly individuals high levels of interleukin-1beta (IL-1beta) in the brain
      have been implicated in infection-related behavioral pathologies but this has not
      been directly tested. Therefore, the current study investigated if sickness
      behavior in aged animals elicited by peripheral injection of lipopolysaccharide
      (LPS) is mediated through central IL-1beta. Adult and aged mice were injected
      intracerebroventricularly with either saline or IL-1ra (4mug) immediately prior
      to intraperitoneal administration of saline or LPS (10mug) and locomotor and
      social behaviors were assessed. As anticipated, LPS depressed locomotor activity
      and social behavior in both adult and aged mice but the behavioral deficits were
      markedly greater in the aged at 24h. Pretreatment with IL-1ra did not affect LPS
      induced sickness behavior in adults; however, in aged mice IL-1ra attenuated LPS
      induced sickness behavior, restoring it to the level exhibited by young adults.
      Twenty-four hours post-injection hippocampal and hypothalamic tissues were
      collected to determine IL-1beta mRNA expression. Neither LPS nor IL-1ra affected
      IL-1beta mRNA levels in adults, presumably because any effect of LPS had
      dissipated by 24h. In contrast, IL-1beta mRNA was markedly higher in aged mice
      24h after LPS, and prior treatment with IL-1ra either blocked or attenuated this
      effect in the hippocampus and hypothalamus, respectively. Taken together these
      data provide the first direct evidence that central IL-1beta is responsible for
      the severe sickness behavior observed in aged animals after LPS treatment. Thus,
      inhibiting the central actions of IL-1beta may be useful for minimizing
      behavioral complications in older individuals with an infection.

PMID- 19152834
TI  - Noradrenergic neurons expressing Fos during waking and paradoxical sleep
      deprivation in the rat.
AB  - Noradrenaline is known to induce waking (W) and to inhibit paradoxical sleep (PS
      or REM). Both roles have been exclusively attributed to the noradrenergic neurons
      of the locus coeruleus (LC, A6), shown to be active during W and inactive during
      PS. However, the A1, A2, A5 and A7 noradrenergic neurons could also be
      responsible. Therefore, to determine the contribution of each of the
      noradrenergic groups in W and in PS inhibition, rats were maintained in
      continuous W for 3h in a novel environment or specifically deprived of PS for 3
      days, with some of them allowed to recover from this deprivation. A double
      immunohistochemical labeling with Fos and tyrosine hydroxylase was then
      performed. Thirty percent of the LC noradrenergic cells were found to be Fos
      positive after exposure to the novel environment and less than 2% after PS
      deprivation. In contrast, a significant number of double-labeled neurons (up to
      40% of the noradrenergic neurons) were observed in the A1/C1, A2 and A5 groups,
      after both novel environment and PS deprivation. After PS recovery and in control
      condition, less than 1% of the noradrenergic neurons were Fos-immunoreactive,
      regardless of the noradrenergic group. These results indicate that the brainstem
      noradrenergic cell groups are activated during W and silent during PS. They
      further suggest that the inhibitory effect of noradrenaline on PS may be due to
      the A1/C1, A2 and to a lesser degree to A5 neurons but not from those of the LC
      as previously hypothesized.

PMID- 19152835
TI  - Prediction of drug distribution within blood.
AB  - Drug distribution in blood, defined as drug blood-to-plasma concentration ratio
      (R(b)), is a fundamental pharmacokinetic parameter. It relates the plasma
      clearance to the blood clearance, enabling the physiological interpretation of
      this parameter. Although easily experimentally determined, R(b) values are
      lacking for the vast majority of drugs. We present a systematic approach using
      mechanistic, partial least squares (PLS) regression and artificial neural network
      (ANN) models to relate various in vitro and in silico molecular descriptors to a
      dataset of 93 drug R(b) values collected in the literature. The ANN model
      resulted in the best overall approach, with r(2)=0.927 and r(2)=0.871 for the
      train and the test sets, respectively. PLS regression presented r(2)=0.557 for
      the train and r(2)=0.656 for the test set. The mechanistic model provided the
      worst results, with r(2)=0.342 and, additionally, is limited to drugs with a
      basic ionised group with pKa<7. The ANN model for drug distribution in blood can
      be a valuable tool in clinical pharmacokinetics as well as in new drug design,
      providing predictions of R(b) with a percentage of correct values within a 1.25
      fold error of 86%, 84% and 87% in the train, test and validation set of data.

PMID- 19152836
TI  - Expression, purification and characterization of aprotinin and a human analogue
      of aprotinin.
AB  - Aprotinin is a Kunitz-type inhibitor with a relatively broad specificity. It has
      been shown to be clinically useful for the management of hemorrhagic
      complications. In this report, small ubiquitin-related modifier (SUMO) linked
      with a hexa-histidine tag was used as a fusion partner for the production of
      recombinant aprotinin and a human aprotinin analogue (cloned form human cDNA
      library). Both fusion proteins were overexpressed mainly as inclusion bodies in
      Escherichia coli and accounted for approximately 28% of the total cell proteins.
      After purification by Ni-Sepharose affinity chromatography and renaturation, the
      fusion proteins were cleaved with SUMO protease 1. Aprotinin and its analogue
      were separated from the fusion partner by the subtractive chromatography using Ni
      Sepharose and then further purified with CM-cellulose. Kinetic studies
      demonstrated that the amidolytic activity of plasmin was competitively inhibited
      by recombinant aprotinin with a K(i) of 8.6+/-2.4 nM, which was similar to the
      K(i) (7.5+/-2.7 nM) of natural aprotinin. The K(i) of human aprotinin analogue
      was 22.7+/-6.5 nM. The expression strategy described in this study allows
      convenient high yield and easy purification of small recombinant protease
      inhibitors with complete native sequences.

PMID- 19152837
TI  - Multiple gene genealogies and phenotypic data reveal cryptic species of the
      Botryosphaeriaceae: a case study on the Neofusicoccum parvum/N. ribis complex.
AB  - Neofusicoccum parvum and N. ribis (Botryosphaeriaceae, Ascomycetes) are closely
      related, plant pathogenic fungi with a world-wide distribution on a wide range of
      woody hosts. Species boundaries in the N. parvum/N. ribis complex have eluded
      definition, despite the application of various tools for characterisation. In
      this study, we test the hypothesis that only one species exists amongst isolates
      from the N. parvum/N. ribis complex, identified from Syzygiumcordatum trees
      across their native distribution in South Africa. Genealogical concordance
      phylogenetic species recognition (GCPSR) was applied based on concordance of
      genealogies obtained from DNA sequence data for five nuclear loci. These data
      showed that the single species hypothesis must be rejected. Rather, all analyses
      support the existence of three previously unrecognised, cryptic species within
      the N. parvum/N.ribis complex from S. cordatum, in addition to N. parvum and N.
      ribis. The three lineages reflecting these cryptic taxa are sympatric across
      their geographical range, indicating barriers to gene flow other than geographic
      isolation. Phenotypic characters failed to detect all the species uncovered by
      the GCPSR. Sequence data of the Internal Transcribed Spacer (ITS) of the
      ribosomal DNA locus, which is thought to be useful for barcoding in fungi, did
      not distinguish all the species with confidence. RNA polymerase II subunit (RPB2)
      was the most informative to distinguish all the species a posteriori to the
      application of GCPSR. The results reflect the critical importance of using
      multiple gene genealogies and adequate sampling to identify cryptic species and
      to characterise the true diversity within the Botryosphaeriaceae.

PMID- 19152838
TI  - Expression of three gonadotropin subunits in Southern catfish gonad and their
      possible roles during early gonadal development.
AB  - The three gonadotropin (GtH) subunit cDNAs, GtHalpha, FSHbeta and LHbeta, which
      contain complete open reading frames were isolated from Southern catfish (Silurus
      meridionalis Chen) ovary. RT-PCR revealed that GtHalpha, FSHbeta and LHbeta mRNA
      were expressed in ovary, female and male pituitaries, but not in testis. Ontogeny
      study showed that GtHalpha and FSHbeta expressed in ovary from 25 dah (days after
      hatching) and LHbeta expressed from 40 dah onwards. The expression levels of
      these genes in all-female Southern catfish gonad were down-regulated after
      treatment with tamoxifen from 5 to 25 dah when measured at 65 dah. These results
      indicated the involvement of the three subunits in gonadal development and sexual
      differentiation.

PMID- 19152839
TI  - Targeting virulence: a new paradigm for antifungals.
AB  - In the recent past, we have found ourselves in need of truly novel antifungal
      drugs as drug resistance in fungi has been evolving. Moreover, effective therapy
      has become particularly important as the number of immuno-compromised patients
      with life-threatening fungal infections increases. Fortunately, during the last
      few years, virulence factors of fungi and their inhibitors have, at least to some
      extent, been discovered and characterized. This should provide new options for
      the development of potential antifungal therapeutics. Inhibitors of the secreted
      aspartic proteinase of Candida albicans might turn out to be particularly
      rewarding.

PMID- 19152840
TI  - Translational strategies for development of monoclonal antibodies from discovery
      to the clinic.
AB  - Successful strategies for the development of monoclonal antibodies require
      integration of knowledge with respect to target antigen properties, antibody
      design criteria such as affinity, isotype selection, Fc domain engineering, PK/PD
      properties and antibody cross-reactivity across species from the early stages of
      antibody development. Biophysical measurements are one of the critical components
      necessary for the design of effective translational strategies for lead selection
      and evaluation of relevant animal species for preclinical safety and efficacy
      studies. Incorporation of effective translational strategies from the early
      stages of the antibody development process is a necessity; when considered it not
      only reduces development time and cost, but also fosters implementation of
      rational decision-making throughout all phases of antibody development.

PMID- 19152841
TI  - Comparative proteomic studies of root-microbe interactions.
AB  - The growth and performance of roots are significantly influenced by microbes
      colonizing the rhizosphere, including bacteria, fungi and nematodes. These root
      microbe interactions can be beneficial, neutral or detrimental to the plant host.
      To improve plant growth, the use of specific soil microbes could be an affordable
      and sustainable strategy. A growing number of proteomic studies are focusing on
      determining the effects that microbes have on roots, in order to identify genes
      and proteins that are specifically induced by microbes. Studies have particularly
      focused on two mutualistic symbioses of roots, those of legumes with nitrogen
      fixing rhizobia and those of a large range of plants with mycorrhizal fungi. In
      addition, the pathogenic relationships between roots and endoparasitic nematodes,
      fungi and oomycetes have been studied to unravel the molecular communication
      between roots and pathogenic microbes. These studies have led to new insights
      into the detection of microbial signal molecules by plants, the balancing of
      defense responses, nutrient exchange and the alteration of plant development by
      microbes. This review highlights some of the recent advances gained by proteomic
      studies focusing on symbiotic and pathogenic root-microbe interactions.

PMID- 19152842
TI  - Understanding and utilising mammalian venom via a platypus venom transcriptome.
AB  - Only five mammalian species are known to be venomous, and while a large amount of
      research has been carried out on reptile venom, mammalian venom has been poorly
      studied to date. Here we describe the status of current research into the venom
      of the platypus, a semi-aquatic egg-laying Australian mammal, and discuss our
      approach to platypus venom transcriptomics. We propose that such construction and
      analysis of mammalian venom transcriptomes from small samples of venom gland, in
      tandem with proteomics studies, will allow the identification of the full range
      of mammalian venom components. Functional studies and pharmacological evaluation
      of the identified toxins will then lay the foundations for the future development
      of novel biomedical substances. A large range of useful molecules have already
      been identified in snake venom, and many of these are currently in use in human
      medicine. It is therefore hoped that this basic research to identify the
      constituents of platypus venom will eventually yield novel drugs and new targets
      for painkillers.

PMID- 19152843
TI  - T box transcription antitermination riboswitch: influence of nucleotide sequence
      and orientation on tRNA binding by the antiterminator element.
AB  - Many bacteria utilize riboswitch transcription regulation to monitor and
      appropriately respond to cellular levels of important metabolites or effector
      molecules. The T box transcription antitermination riboswitch responds to cognate
      uncharged tRNA by specifically stabilizing an antiterminator element in the 5'
      untranslated mRNA leader region and precluding formation of a thermodynamically
      more stable terminator element. Stabilization occurs when the tRNA acceptor end
      base pairs with the first four nucleotides in the seven nucleotide bulge of the
      highly conserved antiterminator element. The significance of the conservation of
      the antiterminator bulge nucleotides that do not base pair with the tRNA is
      unknown, but they are required for optimal function. In vitro selection was used
      to determine if the isolated antiterminator bulge context alone dictates the mode
      in which the tRNA acceptor end binds the bulge nucleotides. No sequence
      conservation beyond complementarity was observed and the location was not
      constrained to the first four bases of the bulge. The results indicate that
      formation of a structure that recognizes the tRNA acceptor end in isolation is
      not the determinant driving force for the high phylogenetic sequence conservation
      observed within the antiterminator bulge. Additional factors or T box leader
      features more likely influenced the phylogenetic sequence conservation.

PMID- 19152844
TI  - [Milk adulterated with melamine: another scandal in public health].

PMID- 19152845
TI  - [Drug supply chain safety in hospitals: current data and experience of the
      Grenoble university hospital].
AB  - Drug supply chain safety has become a priority for public health which implies a
      collective process. This process associates all health professionals including
      the pharmacist who plays a major role. The objective of this present paper is to
      describe the several approaches proven effective in the reduction of drug-related
      problem in hospital, illustrated by the Grenoble University Hospital experience.
      The pharmacist gets involved first in the general strategy of hospital drug
      supply chain, second by his direct implication in clinical activities. The
      general strategy of drug supply chain combines risk management, coordination of
      the Pharmacy and Therapeutics Committee, selection and purchase of drugs and
      organisation of drug supply chain. Computer management of drug supply chain is a
      major evolution. Nominative drug delivering has to be a prior objective and its
      implementation modalities have to be defined: centralized or decentralized in
      wards, manual or automated. Also, new technologies allow the automation of
      overall drug distribution from central pharmacy and the implementation of
      automated drug dispensing systems into wards. The development of centralised drug
      preparation allows a safe compounding of high risk drugs, like cytotoxic drugs.
      The pharmacist should develop his clinical activities with patients and other
      health care professionals in order to optimise clinical decisions (medication
      review, drug order analysis) and patients follow-up (therapeutic monitoring,
      patient education, discharge consultation).

PMID- 19152846
TI  - [PICS: pharmaceutical inspection cooperation scheme].
AB  - The pharmaceutical inspection cooperation scheme (PICS) is a structure containing
      34 participating authorities located worldwide (October 2008). It has been
      created in 1995 on the basis of the pharmaceutical inspection convention (PIC)
      settled by the European free trade association (EFTA) in1970. This scheme has
      different goals as to be an international recognised body in the field of good
      manufacturing practices (GMP), for training inspectors (by the way of an annual
      seminar and experts circles related notably to active pharmaceutical ingredients
      [API], quality risk management, computerized systems, useful for the writing of
      inspection's aide-memoires). PICS is also leading to high standards for GMP
      inspectorates (through regular crossed audits) and being a room for exchanges on
      technical matters between inspectors but also between inspectors and
      pharmaceutical industry.

PMID- 19152847
TI  - [Beyond the diagnosis of a genetic disease, the question of informing the
      relatives].
AB  - The examination of a person's genetic characteristics is not a classic
      diagnostic. It concerns the gene pool of an entire family. It is valid in the
      present and may affect some part of the future. The diseases that it reveals,
      sometime very serious ones, may or may not be treated. But genetic advice allows
      sometimes to preventing some of these diseases. The 2004 Bioethics Law makes the
      provision that in case a serious genetic anomaly is diagnosed during the
      examination of a person's genetic characteristics, the medical doctor informs the
      person or its legal representative of the risks that his silence could cause to
      the potentially concerned family members as long as prevention measures or care
      can be offered to them. For these reasons, besides the specificity of the
      diagnostic for the person directly concerned, there is also the question of the
      right of other people, like family members, to be informed of the diagnostic. As
      such, there is an ethical conflict between medical confidentiality owed to each
      patient and the duty of information. The pharmacist must know the medical
      confidentiality rules that frame this information. He must also know the
      different patient attitudes and must be able to encourage him to inform his
      family because the future if not the life of others may depend on this
      information.

PMID- 19152848
TI  - [Public health and the pharmacist: a challenge of importance regarding training].
AB  - Public health aims at preventing, promoting and restoring populations' health. As
      a public health actor, the chemist must be aware of the collective and social
      dimension of health problems. Moreover, in the exercise of his/her duties, the
      chemist has specific public health actions either in a dispensary, or in a
      hospital, or in industries or in new trades related to risk assessment. To fulfil
      these needs, public health teaching tries to pass on both a knowledge, an ability
      and a method. Lectures given all along the pharmaceutical formation will be
      presented. Concerning research and experts' report in public health,
      pharmacoepidemiology and environmental risks assessment and management are the
      most suitable fields for chemists' intervention.

PMID- 19152849
TI  - [Photodynamic therapy: principles and therapeutic indications].
AB  - Photodynamic therapy consists in destroying a tumoral or a non tumoral tissue by
      the effect of both a photosensitizing molecule and a laser light. This simple
      concept has needed numerous years in order to be used in routine treatments with
      both photosensitizers and laser light delivered optimally. Researches in
      chemistry lead to new porphyrin and bacteriochlorophyl derivatives which
      alleviate the decrease of light absorption by endogenous molecules and in
      consequence allow a deeper light penetration. Short half-life of these compounds
      allows an easier treatment monitoring. In parallel, improvements in both laser
      technology and fibers allow new indications in various pathologies. First
      applications took place in treatment of respiratory, digestive and urologic
      cancers. The biggest success to date is recorded in ophthalmology with the
      treatment of age related macular degeneration. New approaches are explored and
      clinical studies are ongoing.

PMID- 19152850
TI  - [Pharmaceutical consultation for liver transplant patients: a contribution to
      therapeutic education].
AB  - The pharmaceutical consultation offered to liver transplant patients is one of
      the components of therapeutic education. The content of this consultation has
      been designed on the basis of research results led in the field of health
      communication. This research has highlighted the need to clarify to the patient
      the aims and format of the consultation, to obtain patient approval, and to
      elicit patient participation in the elaboration of the treatment plan. Studying
      and taking into account patient representations of transplantation, of transplant
      treatment and rejection is indispensable to the design of an efficient
      communication plan. Setting up this consultation requires initial training or
      continuing vocational training of the pharmacist - this training will address
      issues in psychology, cognitive science and health communication. No such
      training is currently available in universities and needs to be set up. It should
      be followed by practice and training during internships in hospitals and
      community pharmacies.

PMID- 19152851
TI  - [The ignorance of cannabis toxic effects, why should we fight it?].

PMID- 19152852
TI  - Preface. Methods in Enzymology (fluorescence 2008).

PMID- 19152853
TI  - A method in enzymology for measuring hydrolytic activities in live cell
      environments.
AB  - The capability of determining the physiologic role(s) of cellular enzymes
      requires probes with access to all intracellular and extracellular environments.
      Importantly, reporter molecules must be able to cross not only the plasma
      membrane but also enter organelles inside live cells without disturbing the
      physiologic integrity of the system under study. Additionally, each enzyme must
      recognize a probe by the same linear and conformational characteristics as it
      would a physiologic substrate or inhibitor. This chapter focuses on the design
      and use of cell- and tissue-permeable fluorogenic protease substrates. Their
      applications, which are far-reaching, include measurements for apoptosis,
      cytotoxicity, inflammation, cancer metastasis, and viral infections such as HIV.
      Recently, substitution of amino acids with nucleotides in the probe backbone has
      allowed measurements of nuclease activities and hybridization of oligonucleotides
      inside live cells and an example thereof is presented.

PMID- 19152854
TI  - Heterogeneity of fluorescence determined by the method of area-normalized time
      resolved emission spectroscopy.
AB  - Heterogeneity of fluorescence due to multiple fluorophores or emitter species is
      a common problem in using fluorescent molecules to probe the structure, dynamics,
      and properties of microheterogeneous media (micelles, membranes, proteins, etc.)
      and biological media. Time-resolved emission spectra (TRES) and area-normalized
      TRES (TRANES) are useful to identify unambiguously emission from a single species
      (homogeneity) and emission from two species (dual emission). The features in
      TRANES spectra that are characteristic of solvation dynamics associated with
      single species and two species, and many other cases are also described.

PMID- 19152855
TI  - Multiparametric probing of microenvironment with solvatochromic fluorescent dyes.
AB  - We describe new methodology for multiparametric probing of weak non-covalent
      interactions in the medium based on response of environment-sensitive fluorescent
      dyes. The commonly used approach is based on correlation of one spectroscopic
      parameter (e.g. wavelength shift) with environment polarity, which describes a
      superposition of universal and specific (such as hydrogen bonding) interactions.
      In our approach, by using several independent spectroscopic parameters of a dye,
      we monitor simultaneously each individual type of the interactions. For deriving
      these extra parameters the selected dye should exist in several excited and/or
      ground states. In the present work, we applied 4'-(diethylamino)-3
      hydroxyflavone, which undergoes the excited-state intramolecular proton transfer
      (ESIPT) and thus exhibits an additional emission band belonging to an ESIPT
      product (tautomer) form of the dye. The spectroscopic characteristics of the
      excited normal and the tautomer states as well as of the ESIPT reaction of the
      dye are differently sensitive to the different types of interactions with
      microenvironment and therefore can be used for its multiparametric description.
      The new methodology allowed us to monitor simultaneously three fundamental
      physicochemical parameters of probe microenvironment: polarity, electronic
      polarizability and H-bond donor ability. The applications of this approach to
      binary solvent mixtures, reverse micelles, lipid bilayers and binding sites of
      proteins are presented and the limitations of this approach are discussed. We
      believe that the methodology of multiparametric probing will extend the
      capabilities of fluorescent probes as the tools in biomolecular and cellular
      research.

PMID- 19152856
TI  - Site-selective Red-Edge effects.
AB  - Observation of Red Edge effects is the basis of unique methodology that allows
      combination of site-photoselection with dynamics of molecular relaxations. The
      important dynamic information on molecular level can be obtained even by simple
      recording of steady-state fluorescence using the lifetime as the time marker. The
      extension to time domain allows distinguishing these relaxations from other
      dynamic processes that influence the excited-state energies. In this Chapter I
      briefly discuss the background of this technique and concentrate on quantitative
      measure of these effects and on importance of their distinction from ground-state
      heterogeneity. The peculiarity of Trp emission in proteins and the optimal
      selection of fluorescence probes are discussed. The Red Edge excitations
      influence dramatically the excited-state reactions that are coupled with
      dielectric relaxations and this opens a new fascinating prospect for protein and
      biomembrane studies.

PMID- 19152857
TI  - Fluorescence approaches to quantifying biomolecular interactions.
AB  - This review is conceived as an introductory text to aid in the understanding and
      conception of fluorescence-based measurements of biomolecular interactions. The
      major fluorescence observables are introduced briefly. Next, the criteria that
      are involved in the choice of the fluorescent probe are discussed in terms of
      their advantages and disadvantages for different types of experiments. The last
      sections deal with the experimental design for fluorescence-based assays aimed at
      detecting different types of biomolecular interactions. Included in our examples
      are protein-ligand interactions, protein-nucleic acid interactions, aqueous phase
      protein-protein interactions and protein interactions in or at the cell membrane.
      We hope that this introduction will be of use to students and researchers
      considering the use of fluorescence in their work.

PMID- 19152858
TI  - Forster resonance energy transfer measurements of transmembrane helix
      dimerization energetics.
AB  - Lateral interactions between hydrophobic transmembrane (TM) helices in membranes
      underlie the folding of multispan membrane proteins and signal transduction by
      receptor tyrosine kinases (RTKs). Quantitative measurements of dimerization
      energetics in membranes are required to uncover the physical principles behind
      these processes. Here, we overview how FRET measurements can be used to determine
      the thermodynamics of TM helix homo- and heterodimerization in vesicles and in
      supported bilayers. Such measurements can shed light on the molecular mechanism
      behind pathologies arising due to single-amino acid mutations in membrane
      proteins.

PMID- 19152859
TI  - Application of single-molecule spectroscopy in studying enzyme kinetics and
      mechanism.
AB  - This chapter reviews recent developments in the application of single-molecule
      spectroscopy (SMS) to studies of enzyme kinetics and mechanism. Protocols for
      conducting single-molecule experiments on enzymes, based largely on the
      experience in our laboratory, are provided, including methods of sample
      preparation, instrumentation, and data analysis. We also address general issues
      related to the design of meaningful single-molecule experiments and include
      specific examples of the application of SMS to enzyme studies, which reveal new
      and intriguing aspects of enzyme behavior, including static and dynamic
      heterogeneity, as well as subunit cooperativity. Finally, we discuss the
      advantages of employing single-molecule approach in obtaining new information
      beyond ensemble studies.

PMID- 19152860
TI  - Ultrafast fluorescence spectroscopy via upconversion applications to biophysics.
AB  - This chapter reviews basic concepts of nonlinear fluorescence upconversion, a
      technique whose temporal resolution is essentially limited only by the pulse
      width of the ultrafast laser. Design aspects for upconversion
      spectrophotofluorometers are discussed, and a recently developed system is
      described. We discuss applications in biophysics, particularly the measurement of
      time-resolved fluorescence spectra of proteins (with subpicosecond time
      resolution). Application of this technique to biophysical problems such as
      dynamics of tryptophan, peptides, proteins, and nucleic acids is reviewed.

PMID- 19152861
TI  - Use of fluorescence resonance energy transfer (FRET) in studying protein-induced
      DNA bending.
AB  - The specific association of many DNA-binding proteins with DNA frequently results
      in significant deformation of the DNA. Protein-induced DNA bends depend on the
      protein, the DNA sequence, the environmental conditions, and in some cases are
      very substantial, implying that DNA bending has important functional
      significance. The precise determination of the DNA deformation caused by proteins
      under various conditions is therefore of importance for understanding the
      biological role of the association. This review considers methods for the
      investigation of protein-induced DNA bending by measuring the change in
      fluorescence resonance energy transfer (FRET) between fluorophores placed at the
      ends of the target DNA duplex. This FRET technique is particularly efficient when
      the protein-induced bend in the DNA is considerable and results in a significant
      decrease in the distance between the DNA ends bearing the fluorophores. However,
      in the case of small bends the change of distance between the ends of short DNA
      duplexes, as typically used in protein binding experiments (about 16-20 bp), is
      too small to be detected accurately by FRET. In such cases the change of the
      distance between the fluorophores can be increased by using levers attached to
      the binding site, that is, using two bulges to construct a U-shaped DNA in which
      the central part contains the protein-binding site and the fluorophores are
      attached to the ends of the perpendicularly directed arms.

PMID- 19152862
TI  - Fluorescent pteridine probes for nucleic acid analysis.
AB  - This chapter is focused on the fluorescent pteridine guanine analogs, 3MI and 6MI
      and on the pteridine adenine analog, 6MAP. A brief overview of commonly used
      methods to fluorescently label oligonucleotides reveals the role the pteridines
      play in the extensive variety of available probes. We describe the fluorescence
      characteristics of the pteridine probes as monomers and incorporated into DNA and
      review a variety of applications including changes in fluorescence intensity,
      anisotropies, time resolved studies, two photon excitation and single molecule
      detection.

PMID- 19152863
TI  - Single-molecule fluorescence methods for the analysis of RNA folding and
      ribonucleoprotein assembly.

PMID- 19152864
TI  - Using fluorophore-labeled oligonucleotides to measure affinities of protein-DNA
      interactions.
AB  - Changes in fluorescence emission intensity and anisotropy can reflect changes in
      the environment and molecular motion of a fluorophore. Researchers can capitalize
      on these characteristics to assess the affinity and specificity of DNA-binding
      proteins using fluorophore-labeled oligonucleotides. While there are many
      advantages to measuring binding using fluorescent oligonucleotides, there are
      also some distinct disadvantages. Here we describe some of the relevant issues
      for the novice, illustrating key points using data collected with a variety of
      labeled oligonucleotides and the relaxase domain of F plasmid TraI. Topics
      include selection of a fluorophore, experimental design using a fluorometer
      equipped with an automatic titrating unit, and analysis of direct binding and
      competition assays.

PMID- 19152865
TI  - Identifying small pulsatile signals within noisy data: a fluorescence
      application.
AB  - One of the most challenging scientific data analysis quandaries is the
      identification of small intermittent irregularly spaced pulsatile signals in the
      presence of large amounts of heteroscedastic experimental measurement
      uncertainties. We present an application of the use of AutoDecon to a typical
      fluorescence and/or spectroscopic data sampling paradigm, which is to detect a
      single fluorophore in the presence of high background emission. Our calculations
      demonstrate that single events can be reliably detected by AutoDecon with a
      signal-to-noise ratio of 3/20. AutoDecon was originally developed for the
      analysis of pulsatile hormone-concentration time-series data measured in human
      serum. However, AutoDecon has applications within many other scientific fields,
      such as fluorescence measurements where the goal is to count single analyte
      molecules in clinical samples.

PMID- 19152866
TI  - Determination of zinc using carbonic anhydrase-based fluorescence biosensors.
AB  - This chapter summarizes the use of carbonic anhydrase (CA)-based fluorescent
      indicators to determine free zinc in solution, in cells, and in subcellular
      organelles. Expression (both in situ and in vitro) and preparation of CA-based
      indicators are described, together with techniques of their use, and procedures
      to minimize contamination. Recipes for zinc buffers are supplied.

PMID- 19152867
TI  - Instrumentation for fluorescence-based fiber optic biosensors.
AB  - This chapter summarizes the construction principles, operation, and calibration
      of (single-fiber) fluorescence-based fiber optic sensors. These sensors transduce
      recognition of a chemical analyte by a transducer such as a protein molecule as a
      change in fluorescence wavelength or lifetime that can be measured remotely
      through a length of fiber optic. Examples are given of determination of metal
      ions in aqueous solution by fluorescence ratio and lifetime. Included are
      descriptions of instruments, alignment procedures, identification of noise
      sources, use of calibration standards, factors in the use of long fibers for
      sensing, issues in field and shipboard operation, and probe preparation.

PMID- 19152868
TI  - Comparison of one-year outcomes between 23- and 20-gauge vitrectomy for
      preretinal membrane.
AB  - PURPOSE: To compare the outcomes of transconjunctival sutureless 23-gauge
      vitrectomy and conventional 20-gauge vitrectomy 1 year after removal of
      preretinal membrane. DESIGN: Retrospective, consecutive, comparative case series.
      METHODS: One hundred consecutive eyes with a preretinal membrane underwent either
      23- and 20-gauge vitrectomy. The rate of improvement of the logarithm minimum
      angle of resolution visual acuity (VA) was calculated by the formula: (various
      postoperative values-preoperative values) x 100/ (1 year postoperative values
      preoperative values). RESULTS: No significant differences were found between the
      groups in the preoperative and postoperative VAs. The VA improvement was higher
      and the surgically induced corneal astigmatism was lower 1 week postoperatively
      in the 23-gauge group compared with the 20-gauge group (P = .006 and P = .001,
      respectively). The flare values in the anterior chamber measured by laser flare
      meter preoperatively and 1 week postoperatively did not differ between the
      groups. The surgical time was significantly (P = .023) shorter in the 23-gauge
      group than in the 20-gauge group. No apparent complications developed in either
      group. CONCLUSION: Transconjunctival sutureless 23-gauge vitrectomy appears
      effective for preretinal membrane surgery with an acceptable safety profile.
      Transconjunctival sutureless 23-gauge vitrectomy may be a treatment option for
      preretinal membranes.

PMID- 19152869
TI  - Enhanced depth imaging optical coherence tomography of retinal pigment epithelial
      detachment in age-related macular degeneration.
AB  - PURPOSE: To describe the internal structure of pigment epithelial detachments
      (PEDs) seen in eyes with age-related macular degeneration (AMD) as imaged with
      enhanced depth imaging (EDI) spectral-domain optical coherence tomography (OCT).
      DESIGN: Retrospective observational case series. METHODS: The images were
      obtained by positioning a spectral-domain OCT device close enough to the eye to
      obtain an inverted image and 7 sections, each comprised of 100 averaged scans,
      were obtained within a 5 degrees x 15 degrees or larger rectangle to encompass
      the PED and accompanying neovascularization if present. The resultant images were
      reinverted and compared with fluorescein and indocyanine green angiographic
      findings. RESULTS: The full extent of the choroid was visualized under the PED in
      each of the 22 consecutive eyes imaged with EDI OCT. The entire PED cavity filled
      with hyperreflective tissue in 11 eyes. In the remaining 11 regions, what
      appeared to be serous fluid and collections of reflective material were found
      within the PED. The reflective material was seen to be contiguous with subretinal
      pigment epithelial neovascularization, had angiographic suggestive of
      fibrovascular proliferation, and was seen to course up along the back surface of
      the retinal pigment epithelium (RPE). Intravitreal ranibizumab injection caused
      PED flattening with apparent contracture of the accumulated material within the
      PED. CONCLUSIONS: PEDs in the context of AMD show material suggestive of
      choroidal neovascularization, frequently on the back surface of the RPE. These
      findings can help explain the pathogenesis of PEDs, retinal vascular anastomosis
      with choroidal neovascularization, and RPE tears.

PMID- 19152870
TI  - Late recurrence of retinal detachment following successful vitreous surgery for
      stages 4B and 5 retinopathy of prematurity.
AB  - PURPOSE: To determine the incidence and possible causes of a late recurrence of a
      retinal detachment (RD) in eyes with stages 4B and 5 retinopathy of prematurity
      (ROP), in which the retina was once reattached by lensectomy and vitrectomy.
      DESIGN: Retrospective, comparative case series. METHODS: The medical records of
      124 eyes of 99 infants and children <2 years of age at the time of initial
      vitrectomy, in which the retina had been reattached for at least 1 year, were
      reviewed. The incidence of a recurrence of the RD >1 year after the initial
      surgery for eyes at stage 4B ROP (42 eyes) was compared with that in eyes at
      stage 5 ROP (82 eyes). The onset and symptoms were evaluated. RESULTS: A
      recurrent RD occurred in 2 eyes (5%) at stage 4B ROP and 18 eyes (22%) at stage 5
      ROP (P = .01). The recurrence developed at 2 to 10 years of age (median, 4
      years). Prior to the recurrence, clear signs of traction on the peripheral retina
      were detected in 10 eyes (50%): localized residual RDs in 8 eyes, and peripheral
      retinal breaks in 2 eyes. Dense vitreous hemorrhage was present in 5 eyes (25%)
      at the time of the recurrence. CONCLUSIONS: The retina of eyes at stage 5 ROP is
      more vulnerable to a recurrence of the RD than in eyes at stage 4B after being
      attached by vitrectomy. The time of recurrence varies widely, and the presence of
      traction on the peripheral retina may be a sign of a recurrence.

PMID- 19152871
TI  - Five-year follow-up optic disc findings of the Collaborative Initial Glaucoma
      Treatment Study.
AB  - PURPOSE: To determine the effect of intraocular pressure (IOP) lowering on the
      optic disc in patients of the Collaborative Initial Glaucoma Treatment Study
      (CIGTS) after 5 years. DESIGN: Randomized clinical trial. METHODS: The baseline
      and 5-year stereoscopic optic disc photographs of 348 eyes (patients) randomized
      to medical or surgical treatment of open-angle glaucoma (OAG) were assessed by 2
      independent readers for change in a masked side-by-side comparison, and confirmed
      by an independent committee. RESULTS: Three hundred and three (87.1%) eyes showed
      no change, 22 (6.3%) showed enlargement of the cup along any meridian
      (progression), and 23 (6.6%) showed a reduction in the cup along any meridian
      (reversal of cupping). Incidence of optic disc progression was higher (P = .007)
      in the medicine group, 18/185 (10%) than in the surgical group 4/163 (3%); and
      the incidence of reversal of cupping was higher (P < .001) in the surgical group,
      21/163 (13%), than the medicine group, 2/185 (1%), (P < .001). Visual field (VF)
      worsening (mean deviation) was significantly associated with progression of optic
      disc cupping (P < .001). Reversal of cupping was also associated with lower
      postoperative IOP (P < .001). Reversal of cupping was not associated with
      improvement of either visual acuity or central VFs. CONCLUSIONS: Surgery prevents
      or delays glaucomatous progression as measured by optic disc criteria in patients
      with early OAG. Reversal of cupping occurs more frequently in the surgical group
      than in the medical treatment group. Reversal is associated with lower IOP, but
      is not associated with improved visual function.

PMID- 19152872
TI  - Central corneal thickness and its associations with ocular and systemic factors:
      the Singapore Malay Eye Study.
AB  - PURPOSE: To examine the association between central corneal thickness (CCT) and
      potential systemic and ocular factors affecting CCT in an Asian population.
      DESIGN: Population-based cross-sectional study. METHODS: A total of 3,280 (78.7%
      response) adults aged 40 to 80 years of Malay ethnicity living in Singapore
      underwent a standardized interview and ocular and systemic examination at a
      centralized study clinic. CCT was measured with an ultrasound pachymeter. Blood
      samples were obtained to determine serum glucose, cholesterol, and triglyceride
      levels, and urine samples to determine glomerular filtration rate. The presence
      of diabetes, hypertension, chronic kidney disease (CKD), and metabolic syndrome
      were defined based on a combination of investigation results and participant's
      history. RESULTS: CCT was obtained from 3,239 individuals. CCT was normally
      distributed with a mean of 541.2 microm in the right eye. While controlling for
      age and gender, CCT was greater in individuals with higher body mass index (BMI)
      (P = .038), greater intraocular pressure (IOP) (P < .001), greater axial length
      (P = .005), and greater radius of corneal curvature (P < .001). Individuals with
      CKD (P = 0.012) and metabolic syndrome (P < .001) also had greater CCT.
      CONCLUSION: CCT is associated with higher IOP, longer axial length, and greater
      radius of corneal curvature, as well as higher BMI, metabolic syndrome, and CKD.

PMID- 19152874
TI  - Daily mood patterns and bulimic behaviors in the natural environment.
AB  - OBJECTIVE: Negative affect has been purported to play an important role in the
      etiology and maintenance of bulimic behaviors. The objective of this study was to
      identify daily mood patterns in the natural environment exhibited by individuals
      with bulimia nervosa and to examine the relationship between these patterns and
      bulimic behaviors. METHOD: One hundred thirty-three women aged 18-55 meeting DSM
      IV criteria for bulimia nervosa were recruited through clinical referrals and
      community advertisements. Ecological momentary assessment was used to collect
      multiple ratings of negative affect, binge eating and purging each day for a two
      week period using palmtop computers. Latent growth mixture modeling was used to
      identify daily mood patterns. RESULTS: Nine distinct daily mood patterns were
      identified. The highest rates of binge eating and purging episodes occurred on
      days characterized by stable high negative affect or increasing negative affect
      over the course of the day. CONCLUSIONS: These findings support the conclusion
      that negative mood states are intimately tied to bulimic behaviors and may in
      fact precipitate such behavior.

PMID- 19152873
TI  - Retinal vessel diameter and the incidence of coronary artery disease in type 1
      diabetes.
AB  - PURPOSE: To examine the relationship between retinal vessel diameter and coronary
      artery disease (CAD) incidence in type 1 diabetes (T1D) using data from the
      Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. DESIGN:
      Prospective cohort study of childhood-onset T1D. METHODS: Data are from 448
      participants who had retinal photographs taken at baseline examination (May 1986
      to November 1988) and no history of laser photocoagulation. Computer-assisted
      grading was used to measure retinal arteriolar and venular caliber. CAD incidence
      (CAD death, myocardial infarction, revascularization/stenosis > or =50%, ischemic
      electrocardiogram, or physician-diagnosed angina) was ascertained over a median
      follow-up time of 18 years (range, 2 months to 20.5 years). RESULTS: Mean
      baseline arteriolar and venular caliber were 180.0 microm (standard deviation
      [SD], 15.2 microm) and 273.3 microm (SD, 28.0 microm), respectively; 80 (17.9%)
      CAD events occurred during follow-up. After covariate adjustment for T1D
      duration, gender, hypertension, serum lipids, and smoking status, smaller
      arteriolar caliber was significantly associated with CAD (hazard ratio [HR],
      1.42; P = .03), but larger venular caliber was not. A vessel diameter-gender
      interaction term was significant for arteriolar caliber (P = .006). Stratified by
      gender, smaller arteriolar caliber was significantly associated with the
      incidence of CAD in women (HR, 1.92; P = .004), but not men. Venular caliber was
      not associated with CAD in either gender. CONCLUSION: Smaller arteriolar caliber
      may indicate an increased risk of CAD in women, but not men, with T1D. Additional
      studies are needed to further examine the role of microvascular disease in the
      pathogenesis of CAD in women with T1D.

PMID- 19152875
TI  - Recognition and classification of colon cells applying the ensemble of
      classifiers.
AB  - The paper presents the application of an ensemble of classifiers for the
      recognition of colon cells on the basis of the microscope colon image. The solved
      task include: segmentation of the individual cells from the image using the
      morphological operations, the preprocessing stages, leading to the extraction of
      features, selection of the most important features, and the classification stage
      applying the classifiers arranged in the form of ensemble. The paper presents and
      discusses the results concerning the recognition of four most important colon
      cell types: eosinophylic granulocyte, neutrophilic granulocyte, lymphocyte and
      plasmocyte. The proposed system is able to recognize the cells with the accuracy
      comparable to the human expert (around 5% of discrepancy of both results).

PMID- 19152876
TI  - Molecular modeling and dynamics simulation of human cyclin-dependent kinase 3
      complexed with inhibitors.
AB  - The complex CDK3-cyclin is involved in the control of the progression of G0.
      While the mechanisms governing early and late G1 progression are well understood,
      very little is known about the G0-G1 transition. Human CDK3 is closely related to
      cyclin-dependent kinase 2 (CDK2). Since there is no crystallographic structure of
      human CDK3, this work describes for the first time a molecular model of human
      CDK3 complexed with several inhibitors. Comparison of the binary complexes with
      different inhibitors strongly indicates that those inhibitors should inhibit CDK3
      as well as CDK2.

PMID- 19152877
TI  - Embryo quality and implantation rate in two different culture media: ISM1 versus
      Universal IVF Medium.
AB  - OBJECTIVE: To compare the outcome of two different culture media marketed by the
      MediCult AS Company (Jyllinge, Denmark)-Universal IVF Medium and ISM1 Medium
      culture-which, in addition to glucose, pyruvate, and energy-providing components,
      also contain amino acids, nucleotides, vitamins, and cholesterol. DESIGN:
      Laboratory and retrospective clinical study. SETTING: University teaching
      hospital. PATIENT(S): A total of 726 patients, undergoing IVF-intracytoplasmic
      sperm injection procedure, comparable in mean age range, oocyte retrieval, and
      infertility indication, were included in the study. Laboratory quality and
      standard procedures were maintained unaffected. INTERVENTION(S): Oocyte
      retrieval, different embryo culture media. MAIN OUTCOME MEASURE(S): Embryo
      quality, ongoing pregnancy, and implantation rate. RESULT(S): The frequency of
      good-quality embryos (79% vs. 74%) and the percentages of ongoing pregnancy
      (27.5% vs. 18%) and implantation rate (15% vs. 10%) were significantly higher in
      the group treated with ISM1 Medium rather than Universal IVF Medium.
      CONCLUSION(S): ISM1 Medium culture seems to improve the performance of embryonic
      growth and development, as well as increasing the percentage of pregnancy.

PMID- 19152878
TI  - Endometriosis of the soleus and gastrocnemius muscles.
AB  - OBJECTIVE: To document a rare case of endometriosis in the soleus and
      gastrocnemius muscles. DESIGN: Case report. SETTING: Tertiary care center.
      PATIENT(S): A 30-year-old fertile woman presented with moderate dysmenorrhea
      associated with calf pain and bulging that had been gradually worsening over the
      last years, particularly during menses. A mass in the soleus and gastrocnemius
      muscles was identified in ultrasonography and magnetic resonance imaging.
      INTERVENTION(S): Endometriosis was diagnosed by incisional biopsy on the basis of
      histopathology, and wide excisional biopsy was performed. MAIN OUTCOME
      MEASURE(S): Unusual clinical presentation of endometriosis. RESULT(S): The
      patient was disease free for 2 months. Recurrence of the lesion was then
      diagnosed, and a new surgical approach was planned. CONCLUSION(S): Endometriosis
      in muscles is a rare event, and existing theories are not totally sufficient in
      explaining it.

PMID- 19152879
TI  - Successful pregnancy after treatment for ovarian malignant teratoma with growing
      teratoma syndrome.
AB  - OBJECTIVE: To report a case of successful IVF-pregnancy after treatment for
      ovarian growing teratoma syndrome. DESIGN: Case report. SETTING: Gynecologic
      department at a university hospital. PATIENT(S): A 20-year-old woman, gravida 0
      para 0, was diagnosed with malignant teratoma of the ovary. She was treated by
      unilateral salpingo-oophorectomy and chemotherapy. A couple of years later she
      was diagnosed with growing teratoma syndrome. INTERVENTION(S): Fertility
      preserving surgery with unilateral salpingo-oophorectomy and chemotherapy. In
      vitro fertilization. MAIN OUTCOME MEASURE(S): Disease free, successful pregnancy.
      RESULT(S): After treatment for ovarian immature teratoma and growing teratoma
      syndrome the patient was free of the disease. She underwent in vitro
      fertilization treatment with autologous embryo transfer and gave birth to a
      healthy child. CONCLUSION(S): Growing teratoma syndrome is an extremely rare
      metastatic complication of a malignant germ cell tumor after a combination
      treatment with surgery and adjuvant chemotherapy. This case shows that successful
      pregnancy outcome is possible after effective treatment for ovarian growing
      teratoma syndrome.

PMID- 19152880
TI  - Proximal black esophagus: a case report and review of the literature.

PMID- 19152881
TI  - Peroral direct cholangioscopic lithotripsy with a standard upper endoscope for
      difficult bile duct stones (with videos).

PMID- 19152882
TI  - Pericardial tumor diagnosed by EUS-guided FNA (with video).

PMID- 19152883
TI  - Efficacy of a reverse-phase polymer as a submucosal injection solution for EMR: a
      comparative study (with video).
AB  - INTRODUCTION: Reverse-phase polymers undergo a temperature-dependent liquid-to
      gel transition that may provide a more durable cushion for EMR and could yield
      improvements in safety and efficacy. OBJECTIVE: Our purpose was to assess the
      efficacy of poloxamer solution PS137-25 as a submucosal injection. DESIGN:
      Comparative study among 3 different solutions for EMR using ex vivo and in vivo
      porcine models. INTERVENTIONS: A total of 120 gastric submucosal cushions were
      performed in fresh ex vivo porcine stomachs with saline solution 0.9% (n = 40),
      hydroxypropyl methylcellulose (HPMC) (n = 40), and PS137-25 (n = 40). Five in
      vivo porcine colon EMRs were then performed. MAIN OUTCOME MEASUREMENTS: Height
      and duration of submucosal cushions were measured in the ex vivo model, and the
      usefulness of reverse-phase polymers was assessed by in vivo en bloc resection.
      RESULTS: Ex vivo: The height of mucosal elevation was greater with PS137-25 (10.3
      +/- 2.2 mm) than with saline solution (8.3 +/- 2.6 mm) or HPMC (9.05 +/- 2.3 mm,
      not significant). All submucosal elevations with PS137-25 lasted longer (more
      than 20 minutes) than with saline solution (20.9 +/- 11 minutes, P < .01) or HPMC
      (89 +/- 32 minutes, P < .01). After 120 minutes, the elevations obtained with
      PS137-25 showed no differences in size, shape, or consistency from initial
      measurements. In vivo: All 5 EMRs were successfully performed after 1 injection
      of PS137-25. No repeat injections were needed. During resection, a large gel
      cushion was noted. CONCLUSIONS: Mucosal elevation with PS137-25 is more durable
      than with other substances, with no changes in size or consistency observed over
      120 minutes. Additionally, reverse-phase polymers performed well in in vivo colon
      EMRs. These results suggest that reverse-phase polymers may provide increased
      safety and efficacy for EMR procedures.

PMID- 19152884
TI  - Unique endoscopy findings in collagenous colitis.

PMID- 19152885
TI  - Endoscopic transduodenal drainage of an abscess arising after EUS-FNA of a
      duodenal GI stromal tumor.

PMID- 19152886
TI  - Endoscopic snare papillectomy by using a balloon catheter for an unexposed
      ampullary adenoma with intraductal extension (with videos).

PMID- 19152887
TI  - EUS-guided self-expandable stent placement in 1 step: a new method to treat
      pancreatic abscess.

PMID- 19152888
TI  - Esophageal tuberculosis: an unusual cause of dysphagia.

PMID- 19152889
TI  - Endoscopic treatment of recurrent congenital tracheoesophageal fistula with
      Histoacryl glue via the esophagus.

PMID- 19152890
TI  - Transrectal natural orifice transluminal endoscopic surgery for umbilical hernia
      repair in a human cadaver (with video).

PMID- 19152891
TI  - Double-balloon enteroscopy in the diagnosis and treatment of hemorrhage from
      small-bowel lymphangioma: a case report.

PMID- 19152892
TI  - Evaluation and validation of computed virtual chromoendoscopy in early gastric
      cancer.
AB  - BACKGROUND: The Flexible spectral Imaging Color Enhancement (FICE) system
      estimates the spectrum reflectance from a white-light endoscopic image and
      reconstitutes a color image from the wavelength, including useful information
      about the GI tract. The aim of this study was to investigate the usefulness of
      FICE with a specific wavelength in the assessment of early gastric cancers
      (EGCs), and the relationship between the FICE visualization and blood vessels.
      DESIGN: A retrospective study. SETTING: Department of Endoscopy, Hiroshima
      University, Hiroshima, Japan. PATIENTS AND MAIN OUTCOME MEASUREMENTS: The study
      subjects consisted of 100 patients with EGCs (78 differentiated, 22
      undifferentiated) who underwent an endoscopic or surgical resection. We analyzed
      the wavelengths to generate the maximum difference of the spectral reflectance
      between the normal gastric mucosa and the EGCs. We observed the same visual field
      first with white-light endoscopy and then with the FICE system. Then, we scored
      the demarcation of color between the cancer and the normal mucosa of white-light
      endoscopic observation and FICE observation, each without magnification. We
      examined the relationship between the score of the FICE image and the section of
      the vascular space. RESULTS: The wavelength that generated the maximum difference
      in the tissue was 530 nm. The score of the FICE observation improved in 46 cases
      (46%), was unchanged in 54 cases (54%), and decreased in no cases (0%). There was
      a correlation between the score of the FICE images and the section of the
      vascular spaces. CONCLUSIONS: The FICE observation demonstrated that setting the
      wavelength at 530 nm resulted in an improvement in the visualization of the EGCs.
      It is thought that the FICE system is noninvasive and may more easily detect EGC
      without dye during both routine and detailed examinations.

PMID- 19152893
TI  - Submucosal tumor-like mucinous gastric adenocarcinoma showing mucin waterfall.

PMID- 19152894
TI  - Gastric erosion associated with left ventricular assist device: new technology,
      new complication.

PMID- 19152895
TI  - Pancreaticoscopy with miniprobe-based confocal laser-scanning microscopy of an
      intraductal papillary mucinous neoplasm (with video).

PMID- 19152896
TI  - Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of
      the PANDA study.
AB  - BACKGROUND: The role of pancreatic cyst fluid DNA analysis in evaluating
      pancreatic cysts remains unclear. OBJECTIVE: Our purpose was to evaluate the
      utility of a detailed DNA analysis of pancreatic cyst fluid to diagnose mucinous
      and malignant cysts. DESIGN: Prospective, multicenter study. PATIENTS: Patients
      with pancreatic cysts presenting for EUS evaluation. INTERVENTION: EUS-guided
      pancreatic cyst aspirates cytology evaluation, carcinoembryonic antigen (CEA)
      level determination, and a detailed DNA analysis; incorporating DNA
      quantification, k-ras mutation and multiple allelic loss analysis, mutational
      amplitude, and sequence determination. MAIN OUTCOME MEASUREMENTS: Cyst fluid
      analysis compared with surgical pathologic or malignant cytologic examination.
      RESULTS: The study cohort consisted of 113 patients with 40 malignant, 48
      premalignant, and 25 benign cysts. Cyst fluid k-ras mutation was helpful in the
      diagnosis of mucinous cysts (odds ratio 20.9, specificity 96%), whereas receiver
      operator characteristic curve analysis indicated optimal cutoff points for
      allelic loss amplitude (area under the curve [AUC] 0.79; optimal value > 65%) and
      CEA (AUC 0.74; optimal value >148 ng/mL). Components of DNA analysis detecting
      malignant cysts included allelic loss amplitude over 82% (AUC 0.9) and high DNA
      amount (optical density ratio >10, AUC 0.79). The criteria of a high amplitude k
      ras mutation followed by allelic loss showed maximum specificity (96%) for
      malignancy. All malignant cysts with negative cytologic evaluation (10/40) could
      be diagnosed as malignant by using DNA analysis. LIMITATIONS: Limited follow-up,
      selection bias. CONCLUSIONS: Elevated amounts of pancreatic cyst fluid DNA, high
      amplitude mutations, and specific mutation acquisition sequences are indicators
      of malignancy. The presence of a k-ras mutation is also indicative of a mucinous
      cyst. DNA analysis should be considered when cyst cytologic examination is
      negative for malignancy.

PMID- 19152897
TI  - Diagnosing Barrett's esophagus: reliability of clinical and pathologic diagnoses.
AB  - BACKGROUND: The accuracy of a Barrett's esophagus diagnosis is not well studied.
      OBJECTIVE: Our purpose was to evaluate the accuracy of a clinical Barrett's
      esophagus diagnosis and the reproducibility of an esophageal intestinal
      metaplasia diagnosis. METHODS: All patients with a Barrett's esophagus diagnosis
      between 1994 and 2005 were identified by use of International Classification of
      Disease (ICD) and Systematized Nomenclature of Medicine (SNOMED) coding. Subsets
      received manual record review (endoscopy/pathology reports), slide review by a
      referral pathologist (interrater reliability), and 2 blinded reviews by the same
      pathologist (intrarater reliability). SETTING: An integrated health services
      delivery system. MAIN OUTCOME MEASUREMENTS: Accuracy of electronic clinical
      diagnosis and reproducibility of esophageal intestinal metaplasia diagnosis.
      RESULTS: A total of 2470 patients coded with Barrett's esophagus underwent record
      review; a subgroup (616) received manual pathology slide review. Review confirmed
      a Barrett's esophagus diagnosis for 1533 (61.9%) patients: 437 of 798 subjects
      (54.8%) with a SNOMED diagnosis alone, 153 of 671 subjects (26.8%) with an ICD
      diagnosis alone, and 940 of 1101 subjects (85%) who had both a SNOMED and an ICD
      diagnosis. The same metaplasia diagnosis occurred with 88.3% of subjects
      (original vs referral pathologist, interrater reliability; kappa = .42, 95% CI,
      0.34-0.48). The referral pathologist made the same metaplasia diagnosis twice for
      a given patient for 88.6% of subjects (intrarater reliability, 2 reviews by same
      pathologist; kappa = 0.65, 95% CI, 0.35-0.93). LIMITATIONS: The accuracy of a
      Barrett's esophagus diagnosis likely represents the minimum number, given the
      strict criteria. CONCLUSIONS: A community pathologist's diagnosis of esophageal
      intestinal metaplasia is likely to be confirmed by a referral pathologist.
      Electronic diagnoses of Barrett's esophagus overestimate the prevalence, although
      they are usually confirmed in patients with both a SNOMED and ICD diagnosis of
      Barrett's esophagus.

PMID- 19152898
TI  - Successful transgastric drainage of a large mucinous adenocarcinoma of the
      stomach for palliation of malignant gastric luminal obstruction.

PMID- 19152899
TI  - Pneumothorax, pneumomediastinum, pneumoperitoneum, pneumoretroperitoneum, and
      subcutaneous emphysema after ERCP.

PMID- 19152900
TI  - EUS-FNA diagnosis of single pancreatic metastasis of liposarcoma.

PMID- 19152901
TI  - Pancreatic endocrine tumor EUS-guided FNA DNA microsatellite loss and mortality.
AB  - BACKGROUND: The clinical course of pancreatic endocrine tumors (PET) depends on
      tumor size, the presence of invasion or metastasis, the Ki-67 index, mitoses per
      high power field, and mutational damage. Most of this information is not
      available before surgery for clinical decision making or prognostication.
      OBJECTIVE: To evaluate PET EUS-guided FNA (EUS-FNA) microsatellite loss analysis
      in the context of PET-related mortality. DESIGN: A single institution
      retrospective cohort. PATIENTS: Patients with PET diagnosed by EUS-FNA who
      underwent DNA microsatellite loss analysis and at least 1 year of follow-up or
      subsequent death. INTERVENTION: PET microsatellite loss analysis results and
      current clinical status were compared. RESULTS: Twenty-nine patients were
      included in the final analysis; the mean age of the patients was 57 years, and 10
      were women (35%). The mean follow-up was 33.7 months (median 30 months, range 2
      66 months). Twelve patients had disease progression, and 8 died, all from disease
      specific causes. Malignant PET contained multiple microsatellite losses, with a
      median fractional allelic loss (FAL) of 0.37 (range 0.12-0.69, interquartile
      range [IQR] 0.23-0.42), significantly different from benign PET, median FAL 0
      (range 0-0.18, IQR 0-0.08, P < .0001). Survival analysis revealed a significant
      difference in disease recurrence or progression at 2 years (P < .0001) and in the
      5-year survival between patients with FAL </=0.2 compared with >0.2 (P < .0001).
      Logistic regression could not be performed because of the perfect association
      between an FAL >0.2 and disease status or mortality. LIMITATIONS: Retrospective
      design, referral bias, and DNA analysis availability. CONCLUSIONS: PET EUS-FNA
      microsatellite loss analysis provides preoperative prognostic information. An FAL
      >0.2 is not only associated with disease progression but also with mortality.

PMID- 19152902
TI  - Risk factors for the detection of Barrett's esophagus in patients with erosive
      esophagitis.
AB  - BACKGROUND: Barrett's esophagus (BE) results from metaplastic healing of injured
      esophageal mucosa after erosive esophagitis (EE). OBJECTIVE: Our purpose was to
      determine whether severity of esophagitis, indication for endoscopy, or proton
      pump inhibitor treatment affects the subsequent incidence of BE diagnosis in
      patients found to have EE on EGD performed for any indication. DESIGN: We
      identified patients with primary or secondary International Classification of
      Diseases, 9th revision diagnosis codes of EE from 1996 to 2006 who had at least 2
      EGDs on record. Patients with prevalent BE on the first EGD were excluded.
      SETTING: Inpatients and outpatients at Stanford University and Palo Alto Veterans
      Affairs Health Care System. INTERVENTIONS: Retrospective review of EGD and
      pathology reports to confirm BE. MAIN OUTCOME MEASUREMENTS: Detection of BE after
      diagnosis of EE. RESULTS: A total of 1095 patients were identified between 1996
      and 2000, and 102 (9%) were included. Sixty-two (61%) patients were veterans, 87
      (85%) were male, and 83 (81%) were white. The mean (+/-SD) age was 58 +/- 14
      years (range 24-83 years). BE was detected in 9 (9%) patients (95% CI, 4.5%
      17.6%) over a mean of 13.3 +/- 5.7 months (range 1-53.5 months), and all had
      prior grade 4 esophagitis. The mean BE length was 4 +/- 1.8 cm (range 1-18 cm).
      Six patients had upper GI bleeding as the indication for EGD, whereas the other 3
      complained of dysphagia. The association of grade 4 esophagitis (P = .01) and GI
      hemorrhage (P = .01) to the subsequent detection of BE was highly statistically
      significant. LIMITATIONS: Retrospective study, small number of patients with BE
      after EE. All patients were receiving care at tertiary medical centers.
      CONCLUSIONS: BE was detected in 9% of patients with prior EE and was detected
      exclusively on follow-up of patients with severe esophagitis. The majority of the
      patients found to have BE had upper GI bleeding as the presentation for EGD.

PMID- 19152903
TI  - EUS placement of metal fiducials by using a backloaded technique with bone wax
      seal.

PMID- 19152904
TI  - Significance of colonoscope length in cecal insertion time.
AB  - BACKGROUND: According to a previous study, a longer insertion time was associated
      with inadequate bowel cleansing, advanced age, constipation, surgical history,
      sex, and a low body mass index. However, there are only a few studies on the
      association between cecal insertion time and colonoscope length (long vs
      intermediate). OBJECTIVE: To assess the association of colonoscope length and
      cecal insertion time. DESIGN: Prospective comparative trial, with systematic
      assignment to colonoscope length. PATIENTS: A total of 998 colonoscopic
      examinations were performed by a single endoscopist, who used video colonoscopes.
      MAIN OUTCOME MEASUREMENTS: Cecal insertion times and their potential covariates.
      RESULTS: The mean (+/-SEM) age was 49.06 +/- 0.4 years, 61% were men, and the
      mean (+/-SEM) body mass index was 24.17 +/- 2.96. The mean (+/-SEM) cecal
      insertion time was 4.68 +/- 0.09 minutes. Multivariate regression analysis
      demonstrated that sex (female, P = .000), colonoscope length (long, P = .000),
      increasing age (P = .000), percentage of body fat (P = .006), and inadequate
      bowel cleansing (P = .002) were independent factors associated with a longer
      insertion time. LIMITATIONS: All procedures were performed by only one
      gastroenterologist, so the individual characteristics of colonoscopic procedures
      could be affected by a consequent bias. CONCLUSIONS: This large, cross-sectional
      study identified colonoscope length as a useful factor that affected cecal
      insertion time.

PMID- 19152905
TI  - Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk
      lesions: a series of meta-analyses.
AB  - BACKGROUND AND OBJECTIVE: Optimal endoscopic hemostasis remains undetermined.
      This was a systematic review of contemporary methods of endoscopic hemostasis for
      patients with bleeding ulcers that exhibited high-risk stigmata. SETTING:
      Randomized trials that evaluated injection, thermocoagulation, clips, or
      combinations of these were evaluated from MEDLINE, EMBASE, and CENTRAL (1990
      2006). PATIENTS: A total of 4261 patients were evaluated. OUTCOMES: Outcomes were
      rebleeding (primary), surgery, and mortality (secondary). Summary statistics were
      determined; publication bias and heterogeneity were sought by using funnel plots
      or by subgroup analyses and meta-regression. RESULTS: Forty-one trials assessed
      4261 patients. All endoscopic therapies decreased rebleeding versus
      pharmacotherapy alone, including sole intravenous (IV) proton pump inhibition
      (PPI) (OR 0.56 [95% CI, 0.34-0.92]); only one trial assessed high-dose IV PPI.
      Injection alone was inferior compared with other methods, except for thermal
      hemostasis (OR 1.02 [95% CI, 0.74-1.40]), with a strong trend of increased
      rebleeding if 1 injectate is used rather than 2 (OR 1.40 [95% CI, 0.95-2.05]).
      Injection followed by thermal therapy did not decrease rebleeding compared with
      clips (OR 0.82 [95% CI, 0.28-2.38]) or thermal therapy alone (OR 0.79 [95% CI,
      0.24-2.62]). Subgroup analysis, however, suggested that injection followed by
      thermal therapy was superior to thermal therapy alone. Clips were superior to
      thermal therapy (OR 0.24 [95% CI, 0.06-0.95]) but, when followed by injection,
      were not superior to clips alone (OR 1.30 [95% CI, 0.36-4.76]). Surgery or
      mortality was not altered in most comparisons. CONCLUSIONS: All endoscopic
      treatments are superior to pharmacotherapy alone; only 1 study assessed high-dose
      IV PPI. Optimal endoscopic therapies include thermal therapy or clips, either
      alone or in combination with other methods. Additional data are needed that
      compare injection followed by thermal therapy to clips alone or clips combined
      with another method.

PMID- 19152906
TI  - The use of carbon dioxide for insufflation during GI endoscopy: a systematic
      review.
AB  - BACKGROUND: Insufflation of the lumen is required for visualization during GI
      endoscopy. Carbon dioxide (CO(2)) has been proposed as an alternative to room air
      for insufflation. OBJECTIVES: To assess the safety and efficacy of CO(2)
      insufflation for endoscopy. DESIGN: Systematic review that focuses on evidence
      from randomized controlled trials (RCT). METHODS: Two investigators independently
      searched MEDLINE from 1950 to February 13, 2008, to identify all articles that
      reported the use of CO(2) in a GI endoscopy application. Bibliographies of
      relevant articles were also hand searched to identify other pertinent reports.
      Data from RCTs, as well as from nonrandomized studies, were extracted. RESULTS:
      Nine RCTs were identified that compared CO(2) and air insufflation for GI
      endoscopy. Fifteen other nonrandomized studies or reports were also reviewed. In
      the 8 RCTs in which postprocedural pain was assessed, pain was lower in the CO(2)
      insufflation group compared with the air group. Two RCTs found decreased flatus
      in the CO(2) group compared with the air group, and 3 RCTs showed there was
      decreased bowel distention on abdominal radiography in the CO(2) group compared
      with the air group. Also, in all 9 RCTs and 6 additional studies in which safety
      was assessed, there was no CO(2) retention and no adverse pulmonary events
      related to CO(2) insufflation. LIMITATIONS: Because of study heterogeneity, meta
      analytic techniques could not be used. CONCLUSIONS: Consistent RCT evidence
      indicates that CO(2) insufflation is associated with decreased postprocedural
      pain, flatus, and bowel distention. CO(2) insufflation also appears to be safe in
      patients without severe underlying pulmonary disease.

PMID- 19152907
TI  - Portal-vein embolization after sclerotherapy treatment of bleeding gastric
      varices: report of a case with long-term follow-up.

PMID- 19152908
TI  - Left adrenal gland hemorrhage as a complication of EUS-FNA.

PMID- 19152909
TI  - Are bowel purgatives and prokinetics useful for small-bowel capsule endoscopy? A
      prospective randomized controlled study.
AB  - BACKGROUND: Capsule endoscopy (CE) is limited by incomplete small-bowel transit
      and poor view quality in the distal bowel. Currently, there is no consensus
      regarding the use of bowel purgatives or prokinetics in CE. OBJECTIVE: To
      evaluate the usefulness of bowel purgatives and prokinetics in small-bowel CE.
      DESIGN: Prospective single-blind randomized controlled study. SETTING: Academic
      endoscopy unit. PATIENTS: A total of 150 patients prospectively recruited.
      INTERVENTION: Patients were randomized to 1 of 4 preparations: "standard" (fluid
      restriction then nothing by mouth 12 hours before the procedure, water and
      simethicone at capsule ingestion [S]); "standard" + 10 mg oral metoclopramide
      before the procedure (M); Citramag + senna bowel-purgative regimen the evening
      before CE (CS); Citramag + senna + 10 mg metoclopramide before the procedure
      (CSM). MAIN OUTCOME MEASUREMENTS: Gastric transit time (GTT) and small-bowel
      transit time (SBTT), completion rates (CR), view quality, and patient
      acceptability. SECONDARY OUTCOME MEASURES: positive findings, diagnostic yield.
      RESULTS: No significant difference was noted among groups for GTT (median
      [minutes] M, CS, and CSM vs S: 17.3, 24.7, and 15.1 minutes vs 16.8 minutes,
      respectively; P = .62, .18, and .30, respectively), SBTT (median [minutes] M, CS,
      and CSM vs S: 260, 241, and 201 vs 278, respectively; P = .91, .81, and .32,
      respectively), or CRs (85%, 85%, and 88% vs 89% for M, CS, and CSM vs S,
      respectively; P = .74, .74, and 1.00, respectively). There was no significant
      difference in view quality among groups (of 44: 38, 37, and 40 vs 37 for M, CS,
      and CSM, vs S, respectively; P = .18, .62, and .12, respectively). Diagnostic
      yield was similar among the groups. CS and CSM regimens were significantly less
      convenient (P < .001), and CS was significantly less comfortable (P = .001) than
      standard preparation. CONCLUSIONS: Bowel purgatives and prokinetics do not
      improve CRs or view quality at CE, and bowel purgatives reduce patient
      acceptability.

PMID- 19152910
TI  - Endoscopic treatment of gastroesophageal varices in young infants with
      cyanoacrylate glue: a pilot study.
AB  - BACKGROUND: In children, endoscopic sclerotherapy and variceal ligation (EVL) are
      the most used techniques for the treatment of gastroesophageal variceal bleeding
      (VB). However, these techniques achieve poor results in cases of gastric variceal
      bleeding, and EVL is not applicable in young infants. OBJECTIVE: Our purpose was
      to evaluate the feasibility, efficacy, and safety of cyanoacrylate glue injection
      for the treatment of gastroesophageal varices in young infants. DESIGN: Single
      center prospective study. PATIENTS: From 2001 to 2005, 8 young infants (<or=2
      years old, <or=10 kg) with portal hypertension and gastroesophageal varices
      underwent treatment with N-butyl-2-cyanoacrylate. MAIN OUTCOME MEASUREMENTS:
      Demographic data and the results were registered and analyzed at 1, 6, and 12
      months after treatment. RESULTS: The mean age and weight were 1.3 +/- 0.42 years
      (range 0.8 to 1.9 years) and 8.5 +/- 1.6 kg (range 5.5 to 10 kg). Glue injection
      was successfully performed in all infants. The mean volume injected was 1.15 +/-
      0.62 mL (range 0.5 to 2 mL). Immediate control of bleeding was achieved in all
      cases. Ulcer bleeding as a complication was observed in 1 case. Varices relapse
      with bleeding was observed in 3 of 8 (37.5%) patients after a mean of 12.5 +/-
      10.6 weeks (range 5 to 20 weeks). Patients with variceal rebleeding were
      retreated. Varices eradication was achieved in all cases after a mean of 1.4 +/-
      0.52 sessions (range 1 to 2 sessions). LIMITATIONS: Open prospective series with
      a relatively small number of patients. CONCLUSION: In young infants, the use of
      cyanoacrylate glue is safe and effective for the treatment of gastroesophageal
      VB.

PMID- 19152911
TI  - Factors influencing patient satisfaction when undergoing endoscopic procedures.
AB  - BACKGROUND: Limited data are available regarding the best mechanism and timing
      for assessing patient satisfaction with endoscopy. OBJECTIVE: To identify factors
      related to patient satisfaction with endoscopy and to determine if satisfaction
      after the procedure correlates with measurements at a later date. DESIGN: A
      prospective cohort study. SETTING: Tertiary academic hospital. PATIENTS: Patients
      undergoing EGD, colonoscopy, or both. INTERVENTIONS: Patients received
      preprocedure and postprocedure questionnaires on the procedure day. A third
      questionnaire (telephone or mail) was administered at least 1 week later. MAIN
      OUTCOME MEASUREMENTS: Satisfaction scores. RESULTS: A total of 261 patients were
      studied (53% men). The mean age was 55 +/- 14 years. A total of 226 patients
      (86.6%) were very satisfied with their endoscopy. Factors positively associated
      with satisfaction were as follow: doctor's personal manner (odds ratio [OR] 3.00
      [95% CI, 1.80-5.03]), doctor's technical skills (OR 2.65 [95% CI, 1.55-4.51]),
      nurse's personal manner (OR 2.84 [95% CI, 1.74-4.63]), physical environment (OR
      1.75 [95% CI, 1.16-2.64]), and more time with doctor discussing the procedure (OR
      1.66 [95% CI, 1.02-2.69]). Higher levels of pain or discomfort were associated
      with less satisfaction (OR 0.57 [95% CI, 0.36-0.90]). A total of 141 of 261
      patients (54%) were reached for follow-up (mean [SD] 39 +/- 26 days). These
      patients were less satisfied (rating dropped mean 0.35 points, P = .03) than
      those questioned sooner after the procedure and recalled experiencing more pain
      (rating increased mean 0.44 points, P = 0.01). LIMITATION: Single center.
      CONCLUSIONS: This study identified several factors that impacted patient
      satisfaction. Most patients initially appeared very satisfied, perhaps because of
      residual sedation and the distinct setting of the surveys. However, patient
      satisfaction tended to decrease over time, possibly because of recall bias.
      Future studies with patient satisfaction may require assessment at a date further
      removed from their endoscopy.

PMID- 19152912
TI  - Efficacy and safety of the new WallFlex enteral stent in palliative treatment of
      malignant gastric outlet obstruction (DUOFLEX study): a prospective multicenter
      study.
AB  - BACKGROUND: Gastric outlet obstruction (GOO) is most commonly a complication of
      advanced distal gastric, periampullary, or duodenal malignancy. Palliation of
      obstruction is the primary aim of treatment in most of these patients. Self
      expandable metal stents have emerged as an effective treatment option. OBJECTIVE:
      Our purpose was to investigate the efficacy and safety of a newly developed
      enteral metal stent (WallFlex). DESIGN: Prospective multicenter cohort study.
      SETTING: Three tertiary referral centers (2 academic). PATIENTS: Fifty-one
      consecutive patients with symptomatic malignant GOO from January 2005 to February
      2006. INTERVENTION: Placement of a self-expandable metallic stent (WallFlex).
      MAIN OUTCOME MEASUREMENTS: The primary end point was defined as improvement of
      the GOO scoring system for the remainder of the patients' lives. Secondary end
      points focused on efficacy and safety and global quality of life. RESULTS: The
      Gastric Outlet Obstruction Scoring System score improved (P < .001), the body
      mass index decreased (P < .001), and the World Health Organization performance
      score improved (P = .002) when the score before stenting was compared with the
      mean score until death. Global quality of life did not improve. Technical and
      clinical success was achieved in 98% and 84% of the patients. Median survival was
      62 days (75% alive at 35 days, 25% alive at 156 days). Median stent patency was
      307 days (75% functional at 135 days, 25% functional at 470 days). Stent
      dysfunction was proved in 7 patients (14%), migration in 1 (2%), and tumor
      overgrowth or ingrowth in 6 (12%). LIMITATIONS: Lack of a control group.
      CONCLUSION: Placement of a WallFlex enteral stent in patients with nonresectable
      malignant GOO is safe and provides a statistically significant and clinically
      relevant relief of obstructive symptoms with a low need for reintervention.

PMID- 19152913
TI  - Nutrient-mediated teratogenesis and fuel-mediated teratogenesis: two pathways of
      intrauterine programming of diabetes.
AB  - The epidemic of diabetes is spreading quickly to the poor and the deprived.
      Nutrition during fetal life influences the future risk for diabetes; and both
      under- and overnutrition contribute and coexist in rapid-transition countries.
      Nutrient imbalance seems particularly important; for example, low maternal
      vitamin B(12) status coupled with high folate predicted higher adiposity and
      insulin resistance in Indian children, suggesting a role for 1-C (methyl) group
      donors in fetal programming. Maternal hyperglycemia worsens the situation.
      Improving the early-life environment may be more cost-effective for preventing
      diabetes than controlling lifestyle factors alone in later life.

PMID- 19152914
TI  - Catechin reduces atherosclerotic lesion development in apo E-deficient mice: a
      transcriptomic study.
AB  - Much experimental evidence supports a protective role of dietary flavonoids
      against cardiovascular diseases. The aim of the present study was to investigate
      the anti-atherosclerotic effects of catechin supplemented in the diet of apoE
      deficient mice at a low nutritional level and to explore the mechanisms of action
      by a transcriptomic approach. After 6 weeks of supplementation, atherosclerotic
      lesions were assessed by histomorphometry and several markers of lipid,
      inflammation and oxidative stress status were evaluated. Analysis of the global
      gene expression in the aorta was carried out using pangenomic arrays. Catechin
      supplementation reduced the mean atherosclerotic lesion area by 32% but had no
      effect on total cholesterol and triacylglycerol levels in the plasma and the
      liver. The plasma antioxidant capacity (FRAP) and inflammatory status (serum
      amyloid A) were unchanged. The expression of 450 genes was significantly modified
      by catechin supplementation. Some of the most significantly down-regulated genes
      included genes coding for adhesion molecules such as CD34 and PSGL-1 known to
      play a key role in leukocyte adhesion to the endothelium. Other genes involved in
      energy metabolism, lipid metabolism and lipids trafficking such as FABP4, LPL and
      SCARA5 were down-regulated and may contribute to the atheroprotective effect of
      catechin. This work shows that transcriptomic allows characterizing the
      biological effects of low doses of flavonoids where common markers were not
      significantly affected.

PMID- 19152915
TI  - Inflammation and adverse cardiovascular outcome in patients with renal artery
      stenosis and peripheral artery disease.
AB  - OBJECTIVES: We hypothesized that high sensitivity C-reactive protein (hs-CRP) and
      the presence of renal artery stenosis (RAS) might conjointly predict future major
      adverse cardiovascular events (MACE) in patients with peripheral artery disease
      (PAD). BACKGROUND: Clinical outcome in PAD is determined by the extent of
      atherosclerosis affecting additional vascular beds and the activity of the
      atherosclerotic process reflected by inflammatory serum markers. Data on the
      predictive value of hs-CRP on outcome in PAD patients with RAS is limited.
      METHODS: We prospectively enrolled 447 PAD patients who were admitted to our
      institution for angioplasty. Preintervention hs-CRP was assessed and renal
      angiograms were obtained. Patients were then followed clinically for the
      occurrence of MACE for median 15.6 months. Serum creatinine was obtained in all
      patients at 12 months. RESULTS: Incidental RAS >or=60% at baseline was found in
      68 patients (15.2%), MACE were recorded in 111 patients during follow-up. Hs-CRP
      was significantly associated with the occurrence of MACE (p<0.001) and with 12
      months creatinine levels (p=0.005). Adjusted hazard ratios for MACE for
      increasing quartiles of hs-CRP as compared to the lowest quartile were 1.11 (95%
      CI 0.53-2.35), 1.06 (95% CI 0.50-2.26) and 2.79 (95% CI 1.47-5.28). Analyzing
      joint effects of hs-CRP and RAS, we observed no significant interaction.
      CONCLUSION: Hs-CRP predicts cardiovascular and renal outcome in PAD patients
      irrespective of the presence of RAS. Patients with hs-CRP levels above 0.88 mg/dL
      were at particularly high risk for MACE.

PMID- 19152916
TI  - The up-regulation of monocyte chemoattractant protein-1 (MCP-1) in Ea.hy 926
      endothelial cells under long-term low folate stress is mediated by the p38 MAPK
      pathway.
AB  - OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1), encoded by the CCL2 gene,
      plays an important role in the initiation and progression of atherosclerosis.
      Ea.hy 926 endothelial cells grown under low folate conditions (LO cells)
      synthesize more MCP-1 mRNA and secrete more MCP-1 protein than folate-replete
      control cells (HI cells). We investigated the mechanisms underlying the
      modulation of MCP-1 expression by long-term "folate stress". METHODS AND RESULTS:
      CCL2 transcription, assessed using promoter-reporter assays, is up-regulated in
      LO cells relative to HI cells, whereas MCP-1 mRNA stability is unchanged. This
      quantitative transcriptional bias under chronic low folate conditions is not
      attributable to differences in active NF-kappaB, but is associated with elevated
      levels of both total p38 and phospho-p38 that are detectable by Western
      immunoblotting. Transient, acute methotrexate-mediated folate depletion or
      exposure to high concentrations of homocysteine (Hcy) had no effect on MCP-1
      synthesis by Ea.hy 926 cells. The p38 inhibitor SB-203580 abolished the excess
      MCP-1 production by LO cells. The quantitative transcriptional bias of CCL2 in LO
      cells was retained following massive induction by TNF-alpha. CONCLUSION: During
      long-term folate stress, p38 is the primary determinant of CCL2 transcription.
      Long-term folate insufficiency "primes" Ea.hy 926 endothelial cells to have a
      quantitatively more vigorous response to cytokine-mediated inflammatory stress.

PMID- 19152917
TI  - The effect of sliding velocity on chondrocytes activity in 3D scaffolds.
AB  - Sliding motion and shear are important mediators for the synthesis of cartilage
      matrix and surface molecules. This study investigated the effects of velocity
      magnitude and motion path on the response of bovine chondrocytes cultured in
      polyurethane scaffolds and subjected to oscillation against a ceramic ball. In
      order to vary velocity magnitude, the ball oscillated +/-25 degrees at 0.01, 0.1,
      and 1Hz to generate 0.28, 2.8, and 28mm/s, respectively. The median velocity of
      these 'open' motion trajectories was tested against 'closed' motion trajectories
      in that the scaffold oscillated +/-20 degrees against the ball at 1Hz, reaching
      2.8mm/s. Constructs were loaded twice a day for 1h over 5 days. Gene expression
      of cartilage oligomeric matrix protein (COMP), proteoglycan 4 (PRG4, lubricin),
      and hyaluronan synthase 1 (HAS1) and release of COMP, PRG4, and hyaluronan (HA)
      were analyzed. Velocity magnitude determined both gene expression and release of
      target molecules. Using regression analysis, there was a positive and significant
      relationship with all outcome variables. However, only COMP reacted significantly
      at 0.28mm/s, while all other measured variables were considerably up-regulated at
      28mm/s. Motion path characteristics affected COMP, but not PRG4 and HAS1/HA. To
      conclude, velocity magnitude is a critical determinant for cellular responses in
      tissue engineered cartilage constructs. The motion type also plays a role.
      However, different molecules are affected in different ways. A molecule specific
      velocity threshold appears necessary to induce a significant response. This
      should be considered in further studies investigating the effects of continuous
      or intermittent motion.

PMID- 19152918
TI  - Human stability in the erect stance: Alcohol effects and audio-visual
      perturbations.
AB  - AIM: In this article, we discuss the connection between alcohol and the control
      strategies carried out by the central nervous system to maintain the erect
      stance. Audio-visual perturbations were coupled with the consumption of an
      alcoholic beverage to simulate the possible perturbation affecting people at
      disco clubs, and the effects measured with a stabilometric platform. METHODS: We
      studied the statokinesigrams (SKG) of 14 volunteers; 11 of them were healthy, 3
      were injured. We made a series of numerical tests using a stabilometric platform
      to record the statokinesigrams. The tests were carried out using statistical
      methods, time-series analysis, and applying the "p" parameter, recently proposed
      by Pascolo and Marini [2006. On the introduction of a new parameter for the
      analysis of posture. Europa Medicophysica, 42, 145-149] as a new tool to evaluate
      the reactions of the central control system with respect to posture-affecting
      diseases (for instance Parkinson) and perturbations. CONCLUSION: This work shows
      that it is theoretically possible to define non-invasive parameters able to
      distinguish sober subjects from drunk subjects, with an evaluation that only uses
      a stabilometric platform.

PMID- 19152919
TI  - Changes in urinary stone risk factors in hypocitraturic calcium oxalate stone
      formers treated with dietary sodium supplementation.
AB  - PURPOSE: We investigated the effects of supplemental dietary sodium on risk
      factors for urinary stone disease in stone forming patients with hypocitraturia.
      MATERIALS AND METHODS: Ten patients diagnosed with recurrent isolated
      hypocitraturic calcium urolithiasis were identified. Baseline 24-hour urinalysis
      was performed with patients on their regular diet, including citrate replacement
      with 20 mEq potassium citrate 3 times per day. Strict daily dietary logs were
      kept for a 7-day period, during which patients had normal oral intake and
      potassium citrate replacement. Patients then received supplemental sodium
      chloride for 1 week (1 gm orally 3 times per day), in addition to their regular
      diets and potassium citrate supplementation. Dietary logs were continued and 24
      hour urinalysis was performed at the end of 1 week of supplemental sodium. Risk
      factors for urinary stone disease were compared using the Student t test and
      ANOVA. RESULTS: Two patients were unable to comply with sodium supplementation
      based on 24-hour urinalysis and, therefore, they were excluded from study. The
      remaining 8 patients were analyzed. Patients on supplemental dietary sodium
      demonstrated significantly increased mean urinary voided volume (933 ml per day
      above baseline, p <0.05) and mean urinary sodium excretion (66 mEq per day above
      baseline, p <0.05). There was no statistically significant change in urinary
      calcium, oxalate or uric acid. The urinary supersaturation relative risk ratio
      decreased for calcium oxalate stones (0.93 vs 0.63, p <0.05), while those of
      brushite, struvite and uric acid were not different before vs after supplemental
      sodium. CONCLUSIONS: Dietary sodium supplementation resulted in an increased
      voided urine volume and decreased the relative risk supersaturation ratio for
      calcium oxalate stones in patients with a history of hypocitraturic calcium
      oxalate nephrolithiasis. Urinary calcium excretion as well as other urine
      parameters that are risk factors for nephrolithiasis was not changed. Sodium
      restriction may be inappropriate in patients with hypocitraturia and recurrent
      urinary stones. Sodium supplementation may be beneficial in these patients
      because it results in voluntary increased fluid intake.

PMID- 19152921
TI  - Modified York-Mason technique for repair of iatrogenic rectourinary fistula: the
      montsouris experience.
AB  - PURPOSE: Rectourinary fistula is a devastating complication of rectal and
      genitourinary surgery. Spontaneous closure is rarely successful and failure in
      conservative management calls for surgical intervention. We present our
      experience with rectourinary fistula repair using a modified York-Mason
      technique. MATERIALS AND METHODS: We retrospectively reviewed the medical records
      of all 12 patients who underwent modified York-Mason repair at our institution
      between 1998 and 2008. Rectourinary fistula developed in 10 patients after
      radical prostatectomy and in 2 following high intensity focused ultrasound. Six
      patients were initially treated with fecal diversion. Our approach begins with a
      transanal incision at the 2 o'clock position representing a modification of the
      classically described midline incision extending from the coccyx to the anal
      verge. Key aspects of the York-Mason procedure are maintained. However, we do not
      close the urethra after fistula excision, and instead perform a multilayer,
      nonoverlapping closure of the anterior rectal wall only. RESULTS: With a median
      followup of 22 months we observed the complete resolution of rectourinary fistula
      in all 12 patients. Three patients required multiple York-Mason procedures to
      achieve resolution of symptoms. All patients reported intact fecal continence.
      Median operative time and estimated blood loss were 63 minutes and 100 ml,
      respectively. Median hospital stay was 4 days. CONCLUSIONS: Our modified York
      Mason technique is safe and effective for the repair of small, iatrogenic
      rectourinary fistula. We report 75%, 92% and 100% rectourinary fistula resolution
      after 1, 2 and 3 York-Mason procedures, respectively, with 100% fecal continence.
      This technique can be performed multiple times without a significant increase in
      operative time, estimated blood loss or fecal incontinence.

PMID- 19152922
TI  - Recovery of erectile function after unilateral and bilateral cavernous nerve
      interposition grafting during radical pelvic surgery.
AB  - PURPOSE: The use of cavernous nerve interposition grafting to preserve erectile
      function in men who require neurovascular bundle resection for cancer control is
      controversial. We report outcomes and predictors of cavernous nerve interposition
      grafting in men undergoing unilateral grafting during radical prostatectomy or
      bilateral grafting during radical cystectomy and prostatectomy with autologous
      nerve grafts. MATERIALS AND METHODS: We retrospectively reviewed the electronic
      records of 36 patients who underwent cavernous nerve interposition grafting
      between 2003 and 2006. Postoperatively erectile function was assessed with the
      International Index of Erectile Function 15-item questionnaire. Predictors of
      potency, including age at surgery, time since surgery and prostate specific
      antigen at surgery, were assessed by univariate analysis. RESULTS: A total of 33
      patients (92% response rate) were followed for a median of 32, 25 and 11 months
      after bilateral grafting during radical cystectomy (10), unilateral grafting
      during radical prostatectomy (20), and bilateral grafting during radical
      cystectomy and prostatectomy (3), respectively. The rate of potency, defined as
      the ability to attain and maintain erection sufficient for penetration at least
      50% of the time with or without phosphodiesterase-5 inhibitors, was 31% (5 of 13
      men) for unilateral grafts, 38% (5 of 16) for bilateral grafts and 30% (3 of 10)
      for bilateral grafts during radical cystectomy. Age at surgery was the only
      significant determinant of potency and it showed an inverse relationship in the
      bilateral nerve graft group (p = 0.02). CONCLUSIONS: Cavernous nerve
      interposition grafting appears to have a role in the recovery of erectile
      function. To our knowledge this study represents the largest series of cavernous
      nerve interposition grafting during cystectomy and it suggests that this should
      be considered during bilateral neurovascular bundle resection.

PMID- 19152925
TI  - Urinary tract infections in women with type 1 diabetes mellitus: survey of female
      participants in the epidemiology of diabetes interventions and complications
      study cohort.
AB  - PURPOSE: We determined the prevalence of and risk factors for urinary tract
      infection in women with type 1 diabetes, and compared the prevalence of cystitis
      to that in nondiabetic women. MATERIALS AND METHODS: Women enrolled in the
      Epidemiology of Diabetes Interventions and Complications study were surveyed at
      year 10 as part of the Uro-EDIC study to assess the prevalence of cystitis and
      pyelonephritis in the preceding 12 months. Multivariate logistic regression
      models including measures of glycemic control and vascular complications of type
      1 diabetes were used for risk factor analyses. The prevalence of cystitis in Uro
      EDIC women was compared to that in a nondiabetic subset of women participants in
      the National Health and Nutrition Examination Survey III (NHANES III). RESULTS: A
      total of 550 women participated in the Uro-EDIC survey. The prevalence of
      cystitis and pyelonephritis in the preceding 12 months was 15% and 3%,
      respectively. Duration of diabetes, hemoglobin A1C, retinopathy, neuropathy,
      nephropathy, composite vascular complication score and intensive glycemic therapy
      during the Diabetes Control and Complications Trial, and Diabetes Control and
      Complications Trial cohort were not associated with cystitis or pyelonephritis.
      Sexual activity was associated with increased cystitis risk (adjusted OR 8.28;
      95% CI 1.45, 158.32; p = 0.01). The adjusted prevalence of cystitis was 19.1% in
      Uro-EDIC women and 23.1% in NHANES III participants (adjusted OR 0.78; 95% CI
      0.51, 1.22; p = 0.28). CONCLUSIONS: In Uro-EDIC women sexual activity rather than
      measures of diabetes control and complications was the main risk factor for
      urinary tract infection. The prevalence of cystitis was similar to that in
      nondiabetic women participants in NHANES III.

PMID- 19152926
TI  - AUA Best Practice Statement for the prevention of deep vein thrombosis in
      patients undergoing urologic surgery.

PMID- 19152928
TI  - How useful and realistic is the uro trainer for training transurethral prostate
      and bladder tumor resection procedures?
AB  - PURPOSE: We evaluated the face and content validity (novice and expert opinions
      of realism and usefulness) of the Uro Trainer (Karl Storz GmbH, Tuttlingen,
      Germany), a simulator for transurethral resection procedures, to ascertain
      whether it is justifiable to continue the validation process by performing
      prospective experimental studies. MATERIALS AND METHODS: Between 2006 and 2008,
      104 urologists and urology residents performed a transurethral bladder tumor
      resection and/or transurethral prostate resection procedure on the Uro Trainer,
      and rated simulator usefulness and realism on a 10-point scale (1-not at all
      useful/realistic/poor, 10-very useful/realistic/excellent). Participants were
      classified as experts (more than 50 procedures performed) or novices (50 or fewer
      procedures performed). Because the literature offered no guidelines for
      interpreting our data, we used criteria from other studies to interpret the
      results. RESULTS: A total of 161 questionnaires were analyzed from 97 (21%
      experts, 79% novices) and 64 (30% experts, 70% novices) participants who
      performed transurethral prostate resection and transurethral bladder tumor
      resection procedures, respectively. Mean usefulness, realism and overall scores
      varied from 5.6 to 8.2 (SD 1.4-2.5). Measured by validity criteria from other
      studies, Uro Trainer face and content validity was unsatisfactory, with ratings
      on only 3%, 5% and 8% of the parameters interpreted as positive, moderately
      acceptable and good, respectively. CONCLUSIONS: Measured against criteria from
      other validation studies, Uro Trainer face and content validity appears to be
      unsatisfactory. Modification of the simulator seems advisable before further
      experimental validation studies are initiated. The lack of general guidelines for
      establishing face and content validity suggests a need for consensus about
      appropriate methods for evaluating the validity of simulators.

PMID- 19152929
TI  - Use of high fidelity operating room simulation to assess and teach communication,
      teamwork and laparoscopic skills: initial experience.
AB  - PURPOSE: Structured opportunities for learning communication, teamwork and
      laparoscopic principles are limited for urology residents. We evaluated and
      taught teamwork, communication and laparoscopic skills to urology residents in a
      simulated operating room. MATERIALS AND METHODS: Scenarios related to laparoscopy
      (insufflator failure, carbon dioxide embolism) were developed using mannequins,
      urology residents and nurses. These scenarios were developed based on
      Accreditation Council for Graduate Medical Education core competencies and
      performed in a simulation center. Between the pretest scenario (insufflation
      failure) and the posttest scenario (carbon dioxide embolism) instruction was
      given on teamwork, communication and laparoscopic skills. A total of 19 urology
      residents participated in the training that involved participation in at least 2
      scenarios. Performance was evaluated using validated teamwork instruments,
      questionnaires and videotape analysis. RESULTS: Significant improvement was noted
      on validated teamwork instruments between scenarios based on resident (pretest
      24, posttest 27, p = 0.01) and expert (pretest 16, posttest 25, p = 0.008)
      evaluation. Increased teamwork and team performance were also noted between
      scenarios on videotape analysis with significant improvement for adherence to
      best practice (p = 0.01) and maintenance of positive rapport among team members
      (p = 0.02). Significant improvement in the setup of the laparoscopic procedure
      was observed (p = 0.01). Favorable face and content validity was noted for both
      scenarios. CONCLUSIONS: Teamwork, intraoperative communication and laparoscopic
      skills of urology residents improved during the high fidelity simulation course.
      Face and content validity of the individual sessions was favorable. In this study
      high fidelity simulation was effective for assessing and teaching Accreditation
      Council for Graduate Medical Education core competencies related to
      intraoperative communication, teamwork and laparoscopic skills.

PMID- 19152930
TI  - Urinary incontinence among women with type 1 diabetes--how common is it?
AB  - PURPOSE: We compared the prevalence, level of bother and effect on daily
      activities of urinary incontinence among women with type 1 diabetes enrolled in
      the Epidemiology of Diabetes Interventions and Complications study to a
      population based sample of women with normal glucose. MATERIALS AND METHODS: We
      performed a cross-sectional analysis of women with type 1 diabetes and normal
      glucose tolerance using 2 study populations. The Diabetes Control and
      Complications Trial cohort followup, Epidemiology of Diabetes Interventions and
      Complications, began in 1994. In 2004 women participants (550) completed a self
      administered questionnaire on urinary incontinence. Our primary outcome was
      weekly or greater incontinence, overall and by type. Prevalence of urinary
      incontinence was compared to a subgroup of women with normal glucose in the 2001
      to 2002 National Health and Nutrition Examination Survey (NHANES). RESULTS:
      Overall 65% of women with type 1 diabetes reported any urinary incontinence (17%
      reported weekly incontinence). Nearly 40% of these women were greatly bothered by
      their incontinence and 9% believed it affected their day-to-day activities. Women
      with type 1 diabetes had a nearly 2-fold greater prevalence of weekly urge
      incontinence compared to those without diabetes in the NHANES cohort (8.8% vs
      4.5%, p = 0.01). CONCLUSIONS: Urinary incontinence is common in women with type 1
      diabetes and the prevalence of weekly urge incontinence is far greater compared
      to that in women with normal glucose levels. Moreover, the prevalence of urinary
      incontinence in women with type 1 diabetes was greater than that of neuropathy,
      retinopathy and nephropathy. These findings highlight the importance of screening
      for urinary incontinence among women with type 1 diabetes. Studies examining
      factors associated with urinary incontinence in women with type 1 diabetes are
      warranted.

PMID- 19152931
TI  - Histological inflammatory response to transvaginal polypropylene mesh for pelvic
      reconstructive surgery.
AB  - PURPOSE: We prospectively evaluated the histological inflammatory response to the
      large polypropylene transvaginal mesh used for pelvic organ prolapse surgery.
      MATERIALS AND METHODS: Ten patients and 8 controls underwent vaginal punch biopsy
      sampling before surgery and patients also underwent it 1 year after pelvic
      reconstructive surgery using polypropylene mesh. Foreign body response to the
      mesh was assessed using a combination of histological, semiquantitative and
      computerized image based analysis. RESULTS: Compared to preoperative histology
      there was a significant postoperative increase in macrophage and mast cell counts
      (p = 0.03 and 0.01) but no significant changes in the count of cells involved
      primarily in the infectious cell response or collagen density and the elastin
      area fraction at the mesh-tissue interface (p = 0.2 and 0.3, respectively). Three
      cases of mild granuloma formation and 2 of mild erosion were observed. There was
      no significant change in epithelial thickness when comparing preoperative and
      postoperative samples. CONCLUSIONS: When used for pelvic reconstructive surgery,
      macroporous monofilament polypropylene mesh induces a mild but persistent foreign
      body reaction.

PMID- 19152932
TI  - Impact of long-term potassium citrate therapy on urinary profiles and recurrent
      stone formation.
AB  - PURPOSE: Potassium citrate therapy has become one of the cornerstones of medical
      stone management. We elucidated the long-term effects of potassium citrate on
      urinary metabolic profiles and its impact on stone formation rates. MATERIALS AND
      METHODS: We performed a retrospective cohort study in patients treated at the
      Comprehensive Kidney Stone Center at our institution between 2000 and 2006.
      Patients with pre-therapy and post-therapy 24-hour urinary profiles available who
      remained on potassium citrate for at least 6 months were included in the
      analysis. RESULTS: Of the 1,480 patients with 24-hour urinary profiles 503 met
      study inclusion criteria. Mean therapy duration was 41 months (range 6 to 168).
      Overall a significant and durable change in urinary metabolic profiles was noted
      as soon as 6 months after the onset of therapy. These changes included increased
      urinary pH (5.90 to 6.46, p <0.0001) and increased urinary citrate (470 to 700 mg
      a day, p <0.0001). The stone formation rate also significantly decreased after
      the initiation of potassium citrate from 1.89 to 0.46 stones per year (p
      <0.0001). There was a 68% remission rate and a 93% decrease in the stone
      formation rate. CONCLUSIONS: Potassium citrate provides a significant alkali and
      citraturic response during short-term and long-term therapy with the change in
      urinary metabolic profiles sustained as long as 14 years of treatment. Moreover,
      long-term potassium citrate significantly decreases the stone formation rate,
      confirming its usefulness in patients with recurrent nephrolithiasis.

PMID- 19152933
TI  - Seminal plasma survivin in fertile and infertile males.
AB  - PURPOSE: We assessed survivin (an inhibitor of apoptosis) protein in the seminal
      plasma of infertile and fertile males. MATERIALS AND METHODS: Seminal plasma
      survivin was estimated by enzyme-linked immunosorbent assay in 23 healthy fertile
      volunteers, 22 men with oligo-asthenozoospermia, 37 with nonobstructive
      azoospermia and 12 with obstructive azoospermia. Histopathology and testicular
      sperm extraction were done in testicular tissue biopsies from obstructive
      azoospermia and nonobstructive azoospermia cases. RESULTS: Mean seminal survivin
      was highest in fertile controls, less in oligo-asthenozoospermic cases and low in
      nonobstructive azoospermia cases with significant differences. In obstructive
      azoospermia cases seminal plasma survivin was absent. Seminal survivin positively
      correlated with sperm concentration and total sperm motility, and negatively
      correlated with the percent of sperm abnormal forms. Seminal survivin was
      detectable in nonobstructive azoospermia cases in which testicular sperm
      extraction was successful but absent in such cases when testicular sperm
      extraction was unsuccessful. CONCLUSIONS: Seminal survivin is testicular in
      origin. It is related to spermatogenesis and sperm motility processes. Seminal
      survivin was related to successful testicular sperm extraction in nonobstructive
      azoospermia cases.

PMID- 19152934
TI  - A novel pull-through technique for the surgical management of idiopathic
      hydrocele.
AB  - PURPOSE: Standard surgical procedures for hydrocele may cause postoperative
      discomfort, temporary limitation of normal activities and complications, such as
      hematoma, infection, persistent swelling, chronic pain and decreased fertility.
      We describe a new technique in an effort to decrease these complications.
      MATERIALS AND METHODS: Between April 2004 and December 2006, 21 patients
      underwent hydrocelectomy, which was bilateral in 1. Through a 15 mm transverse
      scrotal incision the tunica vaginalis parietalis was identified and grasped.
      Under gentle traction the sac was dissected bluntly and delivered out of the
      incision. The fully mobilized tunica was excised by electrocautery at its base,
      followed by wound closure. Patients were discharged home within 24 hours after
      surgery and were followed at 6-month intervals for a minimum of 18 months.
      RESULTS: Mean operative time was 27.3 minutes. Postoperatively hematoma or wound
      infection was not evident in any case. Mild scrotal edema usually subsided within
      a few days after the procedure. Two patients with persistent edema and hardening
      of the scrotum required additional bed rest and anti-inflammatory agents.
      Patients were able to resume normal daily activity an average of 6 days after
      surgery (range 3 to 21). Cure was achieved in 21 of the 22 hydrocele cases (95%).
      CONCLUSIONS: Our pull-through technique enables the surgeon to remove large
      hydrocele sacs through a small incision and with minimal dissection under direct
      vision of the testicular structures, resulting in early recovery and minimal
      complications. This procedure may be a viable option for the surgical management
      of idiopathic hydrocele.

PMID- 19152935
TI  - Natural history of residual fragments following percutaneous nephrostolithotomy.
AB  - PURPOSE: We reviewed the natural history of residual fragments after percutaneous
      nephrostolithotomy. MATERIALS AND METHODS: From April 1999 to January 2007 a
      total of 728 patients underwent percutaneous nephrostolithotomy at our medical
      center including 527 with a minimum documented radiographic followup of 6 months.
      Of these patients 42 (8%) with residual fragments on postoperative computerized
      tomography were observed rather than subjected to second look flexible
      nephroscopy. Computerized tomography was reviewed to define location, size and
      number of residual fragments. The primary study end point was a stone related
      event defined as growth of a residual fragment, or need for emergency room visit,
      hospitalization or additional intervention attributable to the residual fragment.
      Univariate and multivariate analyses were performed to determine predictors of a
      stone related event. RESULTS: The median residual fragment size was 2 mm (range,
      1 to 12). There were 18 patients (43%) who experienced a stone related event at a
      median of 32 months after percutaneous nephrostolithotomy (range 4 to 95). On
      univariate analysis residual fragment location in the renal pelvis or ureter (p =
      0.02), maximum residual fragment size larger than 2 mm (p = 0.03) and cumulative
      residual fragment size (p = 0.03) predicted a stone related event. On
      multivariate analysis only maximum residual fragment size larger than 2 mm (HR
      3.9, p = 0.01) and location in the renal pelvis or ureter (HR 4.4, p = 0.01)
      independently predicted a stone event. CONCLUSIONS: The size and location of post
      percutaneous nephrostolithotomy residual fragments correlate with stone related
      events. Larger fragments are more likely to require secondary surgical
      intervention. Second look flexible nephroscopy may be of benefit in patients with
      residual fragments larger than 2 mm or in those with fragments located in the
      renal pelvis or ureter.

PMID- 19152936
TI  - Caliceal diverticula in children: natural history and management.
AB  - PURPOSE: The natural history of caliceal diverticula in children is unknown. We
      review our series of children with caliceal diverticula to examine the
      presentation, natural history and management. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 22 children presenting with caliceal
      diverticula between 1983 and 2006. All pertinent clinical data were recorded,
      including demographics, imaging studies, treatment and clinical outcome. RESULTS:
      A total of 22 children had 23 caliceal diverticula. There were 14 girls and 8
      boys who presented at a mean age of 5.4 +/- 3.1 years (range 0.2 to 12). At
      clinical presentation 10 patients had febrile urinary tract infection, 2 had
      hematuria, 2 had abdominal pain, 1 had flank pain and 8 were asymptomatic. Mean
      diameter of all caliceal diverticula was 2.2 +/- 1.7 cm. All patients underwent
      voiding cystourethrogram. Two patients (9%) had concomitant ipsilateral caliceal
      diverticula and vesicoureteral reflux. A total of 10 patients with caliceal
      diverticula (43%) were treated at a mean of 3.0 +/- 2.3 years after initial
      presentation due to symptomatic enlargement in 5, symptomatic calculus in 3,
      complicated abscess in 1 and urosepsis in 1. Treatment modalities included
      percutaneous ablation, open marsupialization/ablation, partial nephrectomy and
      laparoscopic marsupialization/ablation. There were no recurrences during a mean
      followup of 3.1 +/- 2.9 years (range 0.1 to 10.1) in these 10 patients. In the 13
      caliceal diverticula (57%) that were observed mean followup was 6 +/- 3.7 years
      (range 1.2 to 10.5). These caliceal diverticula were stable in size and remained
      asymptomatic. CONCLUSIONS: Caliceal diverticula in children are rare. Most
      caliceal diverticula remain stable and asymptomatic but approximately 20% may
      have symptomatic enlargement that may warrant surgical management. Given the
      morbidity associated with caliceal diverticula and concomitant vesicoureteral
      reflux, evaluation for ipsilateral reflux is mandatory. Overall approximately 43%
      of children with caliceal diverticula require surgical intervention, and various
      treatment options are available.

PMID- 19152937
TI  - Artificial urinary sphincter versus male sling for post-prostatectomy
      incontinence--what do patients choose?
AB  - PURPOSE: Early outcomes of the male sling to correct post-prostatectomy
      incontinence have been promising in select patients. Long-term data are lacking
      to determine whether the male sling is as effective as the artificial urinary
      sphincter, which is the current gold standard. Because the male sling offers the
      significant advantage of avoiding a mechanical device but without established
      success, we determined the patient preference for the male sling vs the
      artificial urinary sphincter. MATERIALS AND METHODS: We reviewed the charts of
      133 men with post-prostatectomy incontinence who underwent the first procedure to
      correct incontinence. After urodynamics the surgeon recommended an artificial
      urinary sphincter or a male sling and patients were told the artificial urinary
      sphincter satisfaction rate and shorter term data on the male sling. Patients
      with high grade post-prostatectomy incontinence (pad weight greater than 400
      gm/24 hours) were recommended to receive an artificial urinary sphincter, those
      with moderate post-prostatectomy incontinence (pad weight 100 to 400 gm/24 hours)
      were recommended to receive an artificial urinary sphincter or a male sling and
      those with mild post-prostatectomy incontinence (pad weight less than 100 gm/24
      hours) were recommended to receive a male sling. RESULTS: A total of 84 male
      sling (63%) and 49 artificial urinary sphincter (37%) procedures were performed.
      The surgeon recommendation was an artificial urinary sphincter in 63 men (47%)
      and a male sling in 46 (35%). A total of 24 men (18%) were given the option of
      either procedure. All patients recommended to receive a male sling chose it. When
      an artificial urinary sphincter was recommended, 75% of patients chose it, while
      25% chose a male sling. When given a choice, 92% of patients chose a male sling
      and 8% chose an artificial urinary sphincter. CONCLUSIONS: Most patients adhere
      to the surgeon recommendation. When men with post-prostatectomy incontinence are
      offered the choice of an artificial urinary sphincter vs a male sling, the
      opportunity to avoid using a mechanical device is preferable to undergoing a well
      established procedure. Men who strongly wish to avoid a mechanical device are
      willing to go against the surgeon recommendation for an artificial urinary
      sphincter.

PMID- 19152938
TI  - Outcome analysis of urethral wall stent insertion with artificial urinary
      sphincter placement for severe recurrent bladder neck contracture following
      radical prostatectomy.
AB  - PURPOSE: We present outcome and quality of life analyses for the treatment of
      post-radical prostatectomy bladder neck contracture with urethral wall stent
      insertion and subsequent artificial urinary sphincter placement. MATERIALS AND
      METHODS: A retrospective analysis from June 2001 to September 2007 identified 25
      consecutive men who underwent urethral wall stent placement for severe, recurrent
      bladder neck contracture despite aggressive transurethral resection after radical
      prostatectomy. Assessment of symptoms and quality of life impact from urinary
      incontinence was conducted with a self-administered, standardized questionnaire.
      Nonparametric testing was used for comparing covariates among groups. Univariate
      Cox proportional hazards modeling was used to assess predictors of treatment
      failure. P values are double-sided and are considered statistically significant
      if </=0.05. RESULTS: Etiology of recurrent bladder neck contracture was radical
      prostatectomy in all patients. Concurrent severe stress incontinence before
      treatment of bladder neck contracture was noted in 23 of 25 patients (92%).
      Before urethral wall stent insertion a median of 3 (IQR 2 to 5) failed endoscopic
      treatments were performed. Bladder neck contracture stabilization with insertion
      of 1 urethral wall stent was noted in 13 of 25 (52%) patients with a median
      followup of 2.9 years from last urethral wall stent insertion. Multiple urethral
      wall stent insertions (range 2 to 4) salvaged an additional 6 of 25 (24%)
      patients and failure to obtain patency was observed in 6 of 25 (24%). All
      patients responded to the questionnaire and quality of life improvement was noted
      in 23 of 25 patients (92%). CONCLUSIONS: Urethral wall stent and delayed
      artificial urinary sphincter placement for treatment of severe, recurrent bladder
      neck contracture and incontinence after radical prostatectomy is associated with
      improvement in quality of life. Long-term followup is required to further
      delineate the efficacy of this treatment approach.

PMID- 19152939
TI  - Perineal anastomotic urethroplasty for posttraumatic urethral stricture with or
      without previous urethral manipulations: a review of 61 cases with long-term
      followup.
AB  - PURPOSE: We retrospectively analyzed cases of anastomotic urethroplasty for
      posttraumatic urethral strictures that were done at our center. Surgical and
      functional outcomes were evaluated. The impact of previous urethral manipulations
      was assessed. MATERIAL AND METHODS: Between 1993 and 2006, 61 males were treated
      with anastomotic urethroplasty because of urethral trauma after pelvic fracture.
      Mean followup was 67 months (range 19 to 173). In 21 of the 61 cases (34.4%)
      urethral manipulation had been performed previously (secondary cases) but had
      failed. All patients were treated via the perineal approach. RESULTS: In 9
      patients (14.8%) recurrence was reported. The recurrence rate was higher in
      patients who underwent former treatment than in primary patients (19% vs 12.5%).
      Posttraumatic impotence was reported by 20 patients (32.8%) but in 2 erectile
      function was restored after treatment. One patient had minor stress incontinence.
      In 2 secondary cases the rectum was injured during the procedure but could be
      repaired. CONCLUSIONS: Anastomotic urethroplasty via the perineal approach is an
      excellent treatment for posttraumatic urethral stricture. Results are good at
      long-term followup. Although statistical significance has not been attained,
      failures and complications seem to be higher in patients who have already
      undergone failed urethroplasty.

PMID- 19152940
TI  - Semirigid ureteroscopy for ureteral stones: a multivariate analysis of
      unfavorable results.
AB  - PURPOSE: We determined the factors predicting unfavorable results of semirigid
      ureteroscopy for ureteral calculi. MATERIALS AND METHODS: We reviewed the
      computerized files of 841 patients who underwent a total of 908 ureteroscopic
      procedures for ureteral stones from January 2003 through December 2006. A
      semirigid 6/7.5Fr ureteroscope was used in pediatric patients and an 8/10Fr or
      8.5/11.5Fr ureteroscope was used in adults. Patients with favorable results were
      those who became stone-free after a single ureteroscopic procedure without any
      complications. They were compared with patients who had unfavorable results using
      univariate (chi-square and t tests) and multivariate (logistic regression)
      statistical tests to identify risk factors for unfavorable results. RESULTS: The
      study included 567 males and 274 females with a mean age of 48.5 years (range 2
      to 81). The complication rate was 6.7% (61 procedures). The stone-free rate after
      a single ureteroscopic intervention was 87% (791 procedures). Favorable results
      were documented in 751 procedures (82.7%). Significant factors for unfavorable
      results were proximal ureteral stones, ureteroscopy done by surgeons other than
      experienced endourologists, stone impaction and stone width (relative risk 4,
      2.5, 1.8 and 1.2, respectively). CONCLUSIONS: Semirigid ureteroscopy is a safe
      and highly effective treatment modality for ureteral stones.

PMID- 19152942
TI  - The relationship between COL3A1 exon 31 polymorphism and pelvic organ prolapse.
AB  - PURPOSE: We investigated the role of COL3A1 exon 31 polymorphism (a single base
      substitution from guanine to adenine at +2092), resulting in the replacement of
      alanine with threonine at the 698th amino acid of COL3A1, in the pathogenesis of
      pelvic organ prolapse. MATERIALS AND METHODS: A total of 72 postmenopausal Korean
      women who were not on hormonal replacement therapy and who had a history of
      vaginal childbirth were enrolled in this study. The patient group consisted of 36
      women diagnosed with stage II or greater pelvic organ prolapse irrespective of
      urodynamic stress incontinence. The control group consisted of 36 healthy
      volunteers with pelvic organ prolapse quantification system stage 0 or I disease
      without urodynamic stress incontinence. After extracting the genomic DNA from
      peripheral blood leukocytes the polymorphism of exon 31 of COL3A1 was typed by
      restriction fragment length polymorphism (Alu I restriction fragment length
      polymorphism) and confirmed by direct sequencing. RESULTS: Frequency of the G
      allele was significantly higher in patients with pelvic organ prolapse than in
      controls (0.8 vs 0.6, p = 0.002). In women with the G allele the OR for pelvic
      organ prolapse was 3.2 (95% CI 1.4-7.3). CONCLUSIONS: COL3A1 exon 31 polymorphism
      may have a role in determining the risk of pelvic organ prolapse in women with
      risk factors such as aging, vaginal childbirth and hypoestrogenism.

PMID- 19152943
TI  - The effect of ankle position on pelvic floor muscle contraction activity in
      women.
AB  - PURPOSE: Stress urinary incontinence is extremely common in women. Conservative
      management includes pelvic floor muscle exercises to increase strength and
      muscular contraction forces to improve incontinence. We examined the effects of
      passive and active ankle flexion on pelvic floor muscle activity during
      exercises. MATERIALS AND METHODS: A total of 31 married women performed random
      pelvic floor muscle contractions while standing, and in 8 passive and active
      positions while pelvic floor muscle activity was simultaneously measured by
      electromyography. RESULTS: All ankle positions resulted in greater pelvic floor
      muscle activity than the horizontal foot position. Significantly greater muscle
      activity was seen with ankles in the plantar position with raised arms (p =
      0.0051). CONCLUSIONS: Pelvic floor muscle exercises performed with active ankle
      positions may increase the effectiveness of these exercises. Further studies are
      required to elucidate mechanisms for this finding.

PMID- 19152944
TI  - Repair of giant vesicovaginal fistulas.
AB  - PURPOSE: We evaluated the long-term success rate of an abdominovaginal approach
      using a rotational bladder flap to repair giant vesicovaginal fistula. MATERIALS
      AND METHODS: A total of 35 patients were included in this study. Of these
      patients 28 had a large vesicovaginal fistula and 7 had complete loss of the
      urethral floor. Fistula etiology was secondary to obstructed labor in 25
      patients, the result of iatrogenic surgical injuries in 5, sling erosion in 3 and
      pelvic irradiation in 2. Using combined abdominal and vaginal approaches the
      bladder was bisected sagittally, and a bladder flap was rotated downward and
      medially to fill the extensive fistula defect. An additional vascularized flap
      was interposed in 23 patients including gracilis muscle flap in 13, omental flap
      in 5, peritoneal flap in 2 and Martius flap in 3. RESULTS: Fistulas were
      successfully repaired in 31 of 35 patients (88%). The remaining 4 patients
      underwent surgical correction with a second, more limited repair. This group
      included 2 patients with fistula from obstructed labor, 1 due to sling erosion
      and 1 due to irradiation. CONCLUSIONS: A combined abdominovaginal approach with
      the use of a generous rotational bladder flap for repair of a complex
      vesicovaginal fistula allowed for excellent results. There was a high success
      rate on the first attempt due to the excellent exposure and healthy, well
      vascularized tissue used for repair.

PMID- 19152945
TI  - Centers of excellence concept and penile prostheses: an outcome analysis.
AB  - PURPOSE: Outcome analysis has shown that the center of excellence concept, in
      which all of a specific type of surgery is done by 1 surgeon rather than by
      multiple surgeons in a group, provides superior outcomes for total joint
      replacement, radical cancer and heart valve surgery. We compared penile
      prosthesis implantation outcomes between the center of excellence and multiple
      surgeon approaches in a large, single specialty urological surgical practice.
      MATERIALS AND METHODS: Between February 2001 and August 2004 a total of 57 penile
      prostheses were implanted by 10 surgeons at a large urology practice (multiple
      surgeon group). Between July 2004 and April 2005 a total of 57 penile prostheses
      were placed by a single surgeon (center of excellence group). Chart review of the
      2 patient groups was performed. RESULTS: The patient groups showed no statistical
      differences in age, race, cause of impotence or percent with diabetes. The median
      cylinder length of prostheses placed by the center of excellence surgeon was 2 cm
      greater than the length of the cylinders placed by the multiple surgeon team (p
      <0.0001). Excluding cases requiring additional procedures the median placement
      time was considerably shorter for the center of excellence surgeon than for the
      multiple surgeon team (34 vs 94 minutes, p <0.0001). There were 8 iatrogenic
      failures (infection, erosion and poor positioning) requiring surgical removal in
      the multiple surgeon group but none in the COE group (p <0.05). Although followup
      for the multiple surgeon team was longer, Kaplan-Meier revision-free survival
      curves showed significantly longer survival for the center of excellence group
      (log rank test p = 0.0283). CONCLUSIONS: The center of excellence concept in
      penile prosthesis surgery appears to deliver superior surgical outcomes in terms
      of shorter operative time, longer cylinders and fewer iatrogenic complications.

PMID- 19152948
TI  - Stress and coping of parents of young children diagnosed with bladder exstrophy.
AB  - PURPOSE: Previous studies have examined the psychological impact that living with
      bladder exstrophy has on patients. However, little is known about how parents of
      children diagnosed with this condition are affected. We examine how parents
      caring for children diagnosed with bladder exstrophy are impacted. An increased
      understanding of the stressors these parents face may lead to the development of
      appropriate parenting interventions, which may ultimately affect psychosocial and
      health outcomes in the child. MATERIALS AND METHODS: All parents of children 10
      years and younger treated for bladder exstrophy at our institution were selected
      from a centralized database. A total of 20 parents (65% of the eligible
      population) completed standardized questionnaires assessing pediatric specific
      parenting stress (Pediatric Inventory for Parents) and coping (Ways of Coping
      Questionnaire). RESULTS: Parents identified several common stressors (eg worrying
      about the long-term impact of the illness, helping the child with his/her hygiene
      needs) and overall reported using adaptive ways of coping (ie planful problem
      solving, seeking social support, positive reappraisal). However, when they
      experienced increased stress they reported using more nonadaptive ways of coping
      (ie escape/avoidance and distancing). CONCLUSIONS: Overall the findings of our
      study suggest that parents of children diagnosed with bladder exstrophy
      experience a significant amount of stress. In fact, parents in our study
      indicated experiencing similar frequency and difficulty of stress compared to
      parents of the same aged children diagnosed with type 1 diabetes. Increased
      stress can have negative consequences for parents and children. Future directions
      and implications of these findings are discussed.

PMID- 19152949
TI  - Development of a scoring system from noncontrast computerized tomography
      measurements to improve the selection of upper ureteral stone for extracorporeal
      shock wave lithotripsy.
AB  - PURPOSE: We investigated the role of noncontrast computerized tomography in
      predicting the treatment outcome of shock wave lithotripsy on upper ureteral
      stones to formulate a clinical algorithm to facilitate clinical management.
      MATERIALS AND METHODS: Adult patients with upper ureteral stones confirmed by
      noncontrast computerized tomography and scheduled for primary in situ shock wave
      lithotripsy were prospectively recruited. Standardized treatment was performed on
      each patient. The primary end point was stone-free status at 3 months.
      Pretreatment noncontrast computerized tomography was assessed by a single
      radiologist blinded to the clinical parameters. Predictive values of computerized
      tomography measurements on the treatment outcome were then assessed. RESULTS:
      Between October 2004 and July 2007 a total of 94 patients (60 male and 34 female)
      were recruited for the study. Logistic regression showed that stone volume, mean
      stone density and skin-to-stone distance were potential predictors of successful
      treatment. From ROC curves the optimum cutoff for predicting treatment outcomes
      for stone volume, mean stone density and skin-to-stone distance was 0.2 cc, 593
      HU and 9.2 cm, respectively. A simple scoring system was constructed based on the
      3 factors of stone volume less than 0.2 cc, mean stone density less than 593 HU
      or skin-to-stone distance less than 9.2 cm. The stone-free rate for patients
      having 0, 1, 2 and 3 factors was 17.9%, 48.4%, 73.3% and 100%, respectively
      (linear-by-linear association test 22.83, p <0.001). CONCLUSIONS: Stone volume,
      mean stone density and skin-to-stone distance were potential predictors of the
      successful treatment of upper ureteral stones with shock wave lithotripsy. A
      scoring system based on these 3 factors helps separate patients into outcome
      groups and facilitates treatment planning.

PMID- 19152950
TI  - Perfluorinated organic contaminants in sediment and aquatic wildlife, including
      sharks, from Georgia, USA.

PMID- 19152951
TI  - Glycosylation of sesamol by cultured plant cells.
AB  - The glycosylation of sesamol was investigated using cultured cells of Nicotiana
      tabacum and Eucalyptus perriniana. The cultured suspension cells of N. tabacum
      converted sesamol into its beta-glucoside (7%) as well as the disaccharide,
      sesamyl 6-O-(beta-D-glucopyranosyl)-beta-D-glucopyranoside (beta-gentiobioside,
      30%). On the other hand, sesamyl 6-O-(alpha-L-rhamnopyranosyl)-beta-D
      glucopyranoside (beta-rutinoside, 56%), together with the beta-glucoside (3%),
      was produced when sesamol was incubated with suspension cells of E. perriniana.

PMID- 19152952
TI  - A multilevel analysis of condom use among adolescents in the European Union.
AB  - OBJECTIVES: This study examined which individual and national factors affect
      condom use among adolescents. STUDY DESIGN: Multilevel analysis. METHODS: This
      study reviewed the data on bullying, alcohol use and condom use provided by 18
      European countries and subnational entities in the Health Behaviour in School
      Aged Children survey. Another eight contextual variables were also analysed.
      Three multilevel logistic regression models were applied consecutively (analysing
      for crude geographical and school variance in condom use, adjusting for gender
      and adjusting all variables for one another). RESULTS: Among the 15-year-olds
      studied, 7.0% of the total variance in condom use was explained by school-related
      factors (intraschool-level correlation) and 5.8% by national/subnational factors.
      In the empty model, condom use was significantly associated with gender, alcohol
      consumption, predominant national religion and national prevalence of human
      immunodeficiency virus (HIV). In the full model, there was also a significant
      association with the Human Development Index ranking, gross domestic product,
      Gini coefficient and the Gender-related Development Index. CONCLUSIONS: This
      study suggests that while alcohol, gender, human development level, income,
      religion and HIV prevalence affect condom use in young Europeans, these factors
      do not explain all or even most of the variation. Nonetheless, since some of
      these factors are not traditionally associated with young people's sexual and
      reproductive health, these findings should enable more nuanced health policy
      programming.

PMID- 19152953
TI  - Effects of phonophoresis with Arnica montana onto acute inflammatory process in
      rat skeletal muscles: an experimental study.
AB  - This study aimed at verifying the effects of phonophoresis associated with Arnica
      montana on the acute phase of an inflammatory muscle lesion. Forty Wistar male
      rats (300+/-50 g), of which the Tibialis Anterior muscle was surgically lesioned,
      were divided into four groups (n=10 each): control group received no treatment;
      the ultrasound group (US) was treated in pulsed mode with 1-MHz frequency, 0.5
      W/cm(2) intensity (spatial and temporal average - SATA), duty cycle of 1:2 (2 ms
      on, 4 ms off, 50%), time of application 3 min per session, one session per day,
      for 3 days; the phonophoresis or ultrasound plus arnica (US+A) group was treated
      with arnica with the same US parameters plus arnica gel; and the arnica group (A)
      was submitted to massage with arnica gel, also for 3 min, once a day, for 3 days.
      Treatment started 24h after the surgical lesion. On the 4th day after lesion
      creation, animals were sacrificed and sections of the lesioned, inflamed muscle
      were removed for quantitative (mononuclear and polymorphonuclear cell count) and
      qualitative histological analysis. Collected data from the 4 groups were
      statistically analyzed and the significance level set at p<0.05. Results show
      higher mononuclear cell density in all three treated groups with no significant
      difference between them, but values were significantly different (p<0.0001) when
      compared to control group's. As to polymorphonuclear cell density, significant
      differences were found between control group (p=0.0134) and US, US+A and A
      groups; the arnica group presented lesser density of polymorphonuclear cells when
      compared (p=0.0134) to the other groups. No significant difference was found
      between US and US+A groups. While the massage with arnica gel proved to be an
      effective anti-inflammatory on acute muscle lesion in topic use, these results
      point to ineffectiveness of Arnica montana phonophoresis, US having seemingly
      checked or minimized its anti-inflammatory effect.

PMID- 19152954
TI  - Rapid column-mode removal of arsenate from water by crosslinked poly(allylamine)
      resin.
AB  - Performances of crosslinked poly(allylamine) resin (PAA) as arsenate (As(V))
      adsorbent were studied using a column packed with PAA in hydrochloride form. PAA
      has a high amino group content of 14.6 mmol/g in free amine form and a high
      chloride content of 10.2 mmol/g in hydrochloride form. Its wet volumes in water
      were 4.5 and 3.1 mL/g in hydrochloride and free amine forms, respectively,
      indicating its high hydrophilicity. Breakthrough capacities for As(V) were
      evaluated changing conditions of adsorption operations: pH of feeds from 2.2 to
      7.0, concentration of As(V) in feeds from 0.020 to 2.0 mM, and feed flow rate
      from 250 to 4000 h(-1) in space velocity. Breakthrough capacities increased from
      2.6 to 3.4 mmol/g with a decrease in pH from 7.0 and 2.2, and also from 0.81 to
      2.8 mmol/g with an increase in As(V) concentration from 0.020 to 2.0mM. When feed
      flow rate increased from 250 to 4000 h(-1), breakthrough capacities changed form
      3.5 to 0.81 mmol/g. Because of non-Hofmeister anion selectivity behavior of PAA,
      the interference of chloride and nitrate was minor. Although PAA slightly
      preferred As(V) to sulfate, the latter more markedly interfered with uptake of
      As(V) than chloride and nitrate. Competitive uptake of As(V) and phosphate
      revealed that PAA slightly preferred phosphate to As(V). The adsorbed As(V) was
      quantitatively eluted with 2M HCl and PAA was simultaneously regenerated into
      hydrochloride form. All results were obtained using the same column without
      change of the packed PAA and any deterioration in column performances for 4
      months.

PMID- 19152955
TI  - Short-term exposure to dioxin impairs bone tissue in male rats.
AB  - Chronic and sub-chronic studies in rats have previously shown that dioxin-like
      compounds impair the bone tissue homeostasis. In the present study, tibiae and
      serum were analyzed to study possible effects of short term dioxin exposure on
      rats. Two month old (ca. 200g) male rats were injected with 50microg 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) kg(-1) bw and tibiae were excised 5d following
      the exposure. Bone composition, dimensions and strength were analyzed by pQCT and
      three-point bending test on tibiae. In addition, detailed bone composition was
      analyzed by optical emission spectroscopy (ICP-OES) and Fourier transform
      infrared spectrometry (FTIR). Analysis of the serum bone biomarkers procollagen
      type-I N-terminal propeptide (PINP) and carboxyterminal cross linking
      teleopeptide (CTX) were also performed. pQCT-results showed alterations in the
      metaphysis, with a significant decrease in trabecular bone cross-sectional area (
      19%, p<0.05) and a significant increase in total bone mineral density (+7%,
      p<0.05) in TCDD-exposed rats. Analyses of the bones by ICP-OES and FTIR showed
      that bones from exposed rats had a higher relative proportion of crystalline
      phosphate (+13% for a1080 and +11% for a1113, p<0.05) and lower acid phosphate
      content (-22% for a1145, p<0.05), resembling the composition of more mature
      bones. Serum analysis showed that the bone formation marker PINP was decreased (
      37%, p<0.05) and that the bone resorption marker CTX was increased (+14%, p<0.05)
      indicating a net loss of bone tissue. In conclusion, 5d of exposure to TCDD was
      sufficient to negatively affect bone tissue in male rats.

PMID- 19152956
TI  - An improved method for assessing relative nucleophilic substitution reactivities
      of polychlorinated benzenes.
AB  - An existing substitution reaction method was improved as part of a system to
      measure the persistency of selected chemicals in the environment by evaluating
      their chemical reactivity. Hexachlorobenzene (HCB), pentachlorobenzene, 1,2,4,5
      tetrachlorobenzene and 1,2,4-trichlorobenzene were selected as model compounds.
      Sodium methoxide in methanol was used as a nucleophile and found to be stable for
      at least 35 days after preparation. The substitution reaction system was modified
      so that nitrogen protection was not necessary to avoid oxidation and hydrolysis
      effects, which led to improved results. The reactivity of polychlorinated
      benzenes (PCBz), which substituted chlorine for methoxide according to a second
      order rate constant, increased as the number of chlorine atoms on the benzene
      ring increased. HCB was selected as a standard for the k(2) calculations of the
      substitution reactions. A normalized k(2) (k(N)) was calculated as
      k(N)=k(PCBz)/k(HCB). GC-MS analysis confirmed that the reactions were pure
      nucleophilic aromatic substitutions without side reactions.

PMID- 19152957
TI  - Mapping of background air pollution at a fine spatial scale across the European
      Union.
AB  - BACKGROUND: There is a need to understand much more about the geographic
      variation of air pollutants. This requires the ability to extrapolate from
      monitoring stations to unsampled locations. The aim was to assess methods to
      develop accurate and high resolution maps of background air pollution across the
      EU. METHODS: We compared the validity of ordinary kriging, universal kriging and
      regression mapping in developing EU-wide maps of air pollution on a 1x1 km
      resolution. Predictions were made for the year 2001 for nitrogen dioxide (NO(2)),
      fine particles <10 microm (PM(10)), ozone (O(3)), sulphur dioxide (SO(2)) and
      carbon monoxide (CO) using routine monitoring data in Airbase. Predictor
      variables from EU-wide databases were land use, road traffic, population density,
      meteorology, altitude, topography and distance to sea. Models were developed for
      the global, rural and urban scale separately. The best method to model
      concentrations was selected on the basis of predefined performance measures
      (R(2), Root Mean Square Error (RMSE)). RESULTS: For NO(2), PM(10) and O(3)
      universal kriging performed better than regression mapping and ordinary kriging.
      Validation of the final universal kriging estimates with results from all
      validation sites gave R(2)-values and RMSE-values of 0.61 and 6.73 microg/m(3)
      for NO(2); 0.45 and 5.19 microg/m(3) for PM(10); and 0.70 and 7.69 microg/m(3)
      for O(3). For SO(2) and CO none of the three methods was able to provide a
      satisfactory prediction. CONCLUSION: Reasonable prediction models were developed
      for NO(2), PM(10) and O(3) on an EU-wide scale. Our study illustrates that it is
      possible to develop detailed maps of background air pollution using EU-wide
      databases.

PMID- 19152958
TI  - Long-term safety, tolerability, and efficacy of duloxetine in the treatment of
      fibromyalgia.
AB  - OBJECTIVES: To assess the long-term safety, tolerability, and efficacy of
      duloxetine in patients with fibromyalgia. METHODS: We report results from the 6
      month extension phases of 2 randomized, double-blind, placebo-controlled clinical
      trials having 6-month placebo-controlled phases. In Study 1, all patients
      received duloxetine 120 mg/d after 28 weeks on placebo or duloxetine 60 or 120
      mg/d. In Study 2, patients taking placebo were titrated to duloxetine 60 mg/d
      after 27 weeks on treatment, while duloxetine-treated patients remained on their
      dosages of 60 or 120 mg/d. Safety and tolerability were assessed via
      discontinuation rates, treatment-emergent adverse events (TEAEs), and changes in
      vital signs and laboratory measures. The primary efficacy measure was the Brief
      Pain Inventory average pain severity score. RESULTS: The percentage of patients
      entering and completing the extension phase was 56% (156/278) for Study 1 and 69%
      (140/204) for Study 2. Groups titrating from placebo to duloxetine showed the
      highest discontinuation rates due to an adverse event (Study 1, 25%; Study 2,
      19%) and TEAE rates (Study 1, 82%; Study 2, 77%). The most common TEAEs were
      nausea and dry mouth. No significant within-group changes in blood pressure
      occurred in any group. Significant within-group mean increases in pulse (bpm)
      were observed in the placebo/duloxetine 120 mg group in Study 1 (3.7 [SD = 11.2],
      P <or= 0.01) and the placebo/duloxetine 60 mg group in Study 2 (4.8 [SD = 10.2],
      P <or= 0.001). Most treatment groups showed small mean change improvements in the
      Brief Pain Inventory average pain severity score. CONCLUSIONS: These findings
      support a positive risk/benefit profile for duloxetine in the long-term treatment
      of fibromyalgia.

PMID- 19152959
TI  - Bronchoalveolar lavage fluid in scleroderma interstitial lung disease: technical
      aspects and clinical correlations: review of the literature.
AB  - OBJECTIVES: Bronchoalveolar lavage (BAL) has been used for clinical and research
      purposes in scleroderma interstitial lung disease (SSc-ILD). However,
      inconsistencies regarding technical aspects of BAL are obstacles in the
      reproducibility and interpretation of BAL results. This review summarizes
      clinical correlations and methodological issues of using BAL in the assessment of
      patients with SSc-ILD. In addition, we review the investigational use of BAL in
      SSc-ILD. METHODS: The PubMed database from inception through May 2008 was
      searched using the following keywords: "systemic sclerosis, scleroderma,
      interstitial lung disease, and bronchoalveolar lavage." The search was limited to
      English-language studies that included at least 15 SSc patients that had BAL.
      RESULTS: An increased percentage of neutrophils, eosinophils, and/or lymphocytes,
      often referred to as "alveolitis," was reported in a significant percentage of
      SSc patients (range, 38 to 100%) irrespective of patient selection criteria,
      cytological cutoff values, or technical aspects of BAL processing. Alveolitis is
      associated with more severe lung impairment as defined by lung function tests and
      overall lung high-resolution computed tomography scores, but there is
      insufficient evidence at this time to recommend BAL cytology as an independent
      predictor of outcome in SSc-ILD patients. Myofibroblasts have been cultured from
      BAL fluid, and inflammatory and fibrogenic mediators can be measured in the
      supernatant of BAL fluid from patients with SSc-ILD. CONCLUSIONS: Further studies
      using standardized BAL protocols are required to establish the role of BAL fluid
      in the clinical evaluation of SSc-ILD. When performed for research purposes, BAL
      has provided valuable insight into the pathogenesis of SSc-ILD.

PMID- 19152960
TI  - Polarization optical analysis of the surface structures of various fungi.
AB  - Vicinal hydroxyl groups of the sugar compounds sialic acid and 9-O-acyl sialic
      acid can be visualised for polarization optical analysis on the surface of
      different fungi using several topo-optical reactions. We investigated the
      presence of these molecules in cultures of Cryptococcus neoformans (heterogeneous
      form), Saccharomyces cerevisiae, Candida albicans, Candida glabrata, Candida
      krusei and Candida tropicalis by topo-optical reactions. Additionally, we
      examined brain and stomach tissues of patients with infections by C. neoformans
      and C. albicans, respectively. The results suggest a highly fashioned orientation
      of the sugar chains on the fungal surface. Terminal sialic- and O-acyl sialic
      acid residues are permanently present and orientated in a highly specific way in
      the cell wall of fungi. Based on the polarization optical analysis after the ABT
      r (anisotropic PAS-r), the linear oriented hydroxyl groups of the sugar molecules
      are localized either perpendicular or parallel to the surface coat, depending on
      the species. According to the orientation of the vicinal hydroxyl groups, the
      oligosaccharide chains are orientated vertically. The capsule of the
      heterogeneous form of C. neoformans presented an especially strong metachromatic
      reaction and anisotropy. It is especially remarkable that the sterical
      orientation of sugar chains, and the terminal sialic acid and 9-O-acyl sialic
      acid molecules, was opposite in the inner and outer layer of the capsule.

PMID- 19152961
TI  - Topo-optical investigations of AA-amyloid deposits from various species.

PMID- 19152962
TI  - Comparative efficacies of procalcitonin and conventional inflammatory markers for
      prediction of renal parenchymal inflammation in pediatric first urinary tract
      infection.
AB  - OBJECTIVES: To compare the reliability of procalcitonin (PCT) with conventional
      laboratory parameters in predicting for renal parenchymal inflammation (RPI).
      METHODS: The study cohort consisted of 57 children who were admitted for a first
      episode urinary tract infection. All patients underwent measurement of the
      leukocyte count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),
      and serum PCT. RPI was evaluated by technetium-99m dimercaptosuccinic acid (DMSA)
      scintigraphy within 7 days of admission. If the first DMSA findings were
      abnormal, another analysis was performed 6 months later. The cutoff points for
      ESR, CRP, and PCT were established by comparing the areas under their receiver
      operating characteristic curves. Statistical analysis was performed using 1-way
      analysis of variance. RESULTS: Of the 57 children, 27 were diagnosed with RPI on
      the basis of positive DMSA results. The ESR, CRP, and PCT levels were
      significantly greater (P < .001) in the patients with RPI than in those without
      RPI. In contrast, the leukocyte count was the same in both groups (P > .05). PCT
      was a more sensitive and specific marker for differentiating upper and lower
      urinary tract infection than ESR and CRP. Persistent lesions at the site of
      previous RPI were found in 12 patients in the follow-up DMSA analysis, with total
      regression evident in the remaining 15. The PCT levels were significantly greater
      in those with persistent renal lesions than in those with total regression (P =
      .005). CONCLUSIONS: Serum PCT is a more reliable biologic marker than the ESR,
      CRP, or leukocyte count for the early prediction of RPI in children with a first
      episode of urinary tract infection. In addition, the greater the elevation of PCT
      at admission, the more positive the correlation for subsequent permanent renal
      damage.

PMID- 19152964
TI  - Prenatal determinants of neonatal lung function in high-risk newborns.
AB  - BACKGROUND: Neonatal lung function is suspected to be associated with wheezy
      disorders, but little is known about risk factors for the early lung function.
      OBJECTIVES: To study prenatal determinants of neonatal lung function. METHODS:
      This is a clinical, prospective birth cohort study of 411 newborns, the
      Copenhagen Prospective Study on Asthma in Childhood, in a single-center research
      clinic dedicated solely to this longitudinal birth cohort study. Lung function
      was determined at 1 month of age by infant spirometry (the raised volume rapid
      thoraco-abdominal compression technique) and bronchial responsiveness to
      methacholine by transcutaneous oxygen measurements. Risk factor analyses included
      anthropometrics; demographics; socioeconomic factors; parental atopic history;
      previous deliveries; exposures during the third trimester to the mother's
      smoking, alcohol, and medicines; third trimester pregnancy complications
      including mother's asthma status; and mode of delivery. RESULTS: Lung function
      was determined in 404 neonates, age 6 weeks. Neonates with body mass index in the
      upper quartile had 14% lower baseline forced expiratory volume at 0.5 second, and
      neonates of mothers smoking during the third trimester had 7% lower baseline
      forced expiratory volume at 0.5 second. Sex or parental atopic disease did not
      affect the neonatal lung function and bronchial responsiveness. Maternal intake
      of paracetamol during the third trimester was associated with doubling of the
      bronchial responsiveness in the neonates, but the statistical significance may
      have been driven by outliers. Bronchial responsiveness exhibited a parabola
      development with tripling of bronchial responsiveness reaching the nadir at 3
      months of age, but this needs replication in a study with repetitive measurements
      within individuals. CONCLUSION: High body mass index in newborns and mothers
      smoking is associated with reduced neonatal lung function. This suggests that the
      association between body proportion and wheezing disorders may be a result of
      shared genes or prenatal nutrition.

PMID- 19152963
TI  - Selective deregulation in chemokine signaling pathways of CD4+CD25(hi)CD127(lo)/(
      ) regulatory T cells in human allergic asthma.
AB  - BACKGROUND: CD4+CD25(hi)CD127(lo)/(-) regulatory T cells have been suggested to
      be critical regulators of inflammatory processes in allergic asthma. Recent
      studies reported a selective decrease in the frequency of regulatory T cells in
      the bronchoalveolar lavage fluid of allergic asthmatic (AA) subjects, prompting
      the possibility of defective recruitment of these cells to the airway in response
      to chemokines produced during asthmatic inflammation. OBJECTIVES: This study
      aimed to characterize the chemotactic profile of circulating regulatory T cells
      in AA subjects in response to chemokines abundantly produced in airway
      inflammation, such as CCL1, CCL17, and CCL22. METHODS: The study was performed in
      a cohort of 26 AA, 16 healthy control, and 16 non-AA subjects. We used chemotaxis
      assays to evaluate cell migration, flow cytometry to examine chemokine receptor
      expression, and phospho-ELISA to study consequent signaling pathways in
      regulatory T cells. RESULTS: Regulatory T cells, but not CD4+CD25(-)T cells, from
      AA subjects showed decreased chemotactic responses, specifically to CCL1, in
      comparison with their healthy control and non-AA counterparts. Decreased CCL1
      mediated chemotaxis in AA regulatory T cells was associated with decreased
      phosphorylation of protein kinase B (AKT), a protein involved in chemokine
      intracellular signaling. Furthermore, the decreased chemotactic response to CCL1
      in AA regulatory T cells significantly correlated with asthma severity and
      decreased pulmonary function in AA subjects. CONCLUSIONS: These results provide
      the first evidence of dysfunction in the chemokine signaling pathway in AA
      regulatory T cells.

PMID- 19152965
TI  - Proviral integration site for Moloney murine leukemia virus 1, but not
      phosphatidylinositol-3 kinase, is essential in the antiapoptotic signaling
      cascade initiated by IL-5 in eosinophils.
AB  - BACKGROUND: Eosinophil differentiation, activation, and survival are largely
      regulated by IL-5. IL-5-mediated transmembrane signal transduction involves both
      Lyn-mitogen-activated protein kinases and Janus kinase 2-signal transducer and
      activator of transcription pathways. OBJECTIVE: We sought to determine whether
      additional signaling molecules/pathways are critically involved in IL-5-mediated
      eosinophil survival. METHODS: Eosinophil survival and apoptosis were measured in
      the presence and absence of IL-5 and defined pharmacologic inhibitors in vitro.
      The specific role of the serine/threonine kinase proviral integration site for
      Moloney murine leukemia virus (Pim) 1 was tested by using HIV-transactivator of
      transcription fusion proteins containing wild-type Pim-1 or a dominant-negative
      form of Pim-1. The expression of Pim-1 in eosinophils was analyzed by means of
      immunoblotting and immunofluorescence. RESULTS: Although pharmacologic inhibition
      of phosphatidylinositol-3 kinase (PI3K) by LY294002, wortmannin, or the selective
      PI3K p110delta isoform inhibitor IC87114 was successful in each case, only
      LY294002 blocked increased IL-5-mediated eosinophil survival. This suggested that
      LY294002 inhibited another kinase that is critically involved in this process in
      addition to PI3K. Indeed, Pim-1 was rapidly and strongly expressed in eosinophils
      after IL-5 stimulation in vitro and readily detected in eosinophils under
      inflammatory conditions in vivo. Moreover, by using specific protein transfer, we
      identified Pim-1 as a critical element in IL-5-mediated antiapoptotic signaling
      in eosinophils. CONCLUSIONS: Pim-1, but not PI3K, plays a major role in IL-5
      mediated antiapoptotic signaling in eosinophils.

PMID- 19152966
TI  - Determinants of allergenicity.
AB  - The question "What makes an allergen an allergen?" has puzzled generations of
      researchers, and we still do not have a conclusive answer. Despite increasing
      knowledge about the molecular and functional characteristics of allergens that
      have been identified, we still do not fully understand why some proteins are
      clinically relevant allergens and most are not. Different approaches have been
      taken to identify the structural and functional features of allergens, aiming at
      developing methods to predict allergenicity and thus to identify allergens.
      However, none of these methods has allowed a reliable discrimination between
      allergenic and nonallergenic compounds on its own. This review sums up diverse
      determinants that contribute to the phenomenon of allergenicity and outlines that
      in addition to the structure and function of the allergen, factors derived from
      allergen carriers, the environment, and the susceptible individual are of
      importance.

PMID- 19152967
TI  - A hypoallergenic variant of Der p 1 as a candidate for mite allergy vaccines.
AB  - BACKGROUND: Recombinant hypoallergens that display reduced allergenicity but
      retain T-cell reactivity represent promising candidates to improve the safety and
      efficacy of allergen-specific vaccines or immunotherapy. OBJECTIVE: The current
      study reports the immunologic characterization of a hypoallergenic variant of the
      major mite allergen Der p 1. METHODS: The recombinant proform of Der p 1 (ProDer
      p 1) was expressed in Escherichia coli (ProDer p 1 coli), purified and
      characterized at the level of its secondary structure, and IgE and T-cell
      reactivities. Moreover, the prophylactic potential of ProDer p 1 coli
      vaccinations was evaluated in a murine Der p 1 sensitization model. RESULTS:
      After purification and refolding, ProDer p 1 coli remained aggregated with a
      higher beta-sheet content and altered Der p 1 conformational epitopes compared
      with the correctly folded monomeric ProDer p 1 produced in Chinese hamster ovary
      cells. Both ProDer p 1 forms were able to retain the Der p 1-specific T-cell
      reactivity but direct ELISA, competitive inhibition, and rat basophil leukemia
      assays clearly showed that ProDer p 1 coli displays a very weak IgE reactivity.
      Mice vaccinations with aggregated ProDer p 1 adjuvanted with alum induced a T(H)1
      biased immune response that prevented the subsequent allergic response after Der
      p 1 sensitization and airway challenge with aerosolized mite extracts.
      Furthermore, ProDer p 1 coli treatment inhibited the development of airway
      eosinophilia and airway hyperresponsiveness to inhaled methacholine. CONCLUSION:
      Aggregated forms of Der p 1 could represent hypoallergens suitable for the
      prevention of mite allergy.

PMID- 19152968
TI  - Exposure to traffic: lung function and health status in adults with asthma.
AB  - BACKGROUND: Exposure to traffic has been associated with asthma outcomes in
      children, but its effect on asthma in adults has not been well studied.
      OBJECTIVE: To test the hypothesis that lung function and health status are
      associated with traffic exposures. METHODS: We measured FEV(1) % predicted,
      general health status using the Physical Component Scale of the 12-item Short
      Form (SF-12 PCS), and quality of life (QoL) using the Marks Asthma Quality of
      Life questionnaire in a cohort of adults with asthma or rhinitis (n = 176; 145
      with asthma). We assessed exposures to traffic by geocoding subjects' residential
      addresses and assigning distance to roadways. Associations between distance to
      nearest roadway and distance to nearest major roadway and FEV(1) % predicted or
      SF-12 PCS were studied by using linear regression. RESULTS: FEV(1) % predicted
      was positively associated with distance from both nearest roadway (P = .01) and
      nearest major roadway (P = .02). SF-12 PCS and QoL were not significantly
      associated with either traffic variable. Adjustment for income, smoking, and
      obesity did not substantively change the associations of the traffic variables
      with FEV(1) % predicted (P = .04 for nearest roadway and P = .02 for nearest
      major roadway) and did not cause associations with either SF-12 PCS or QoL to
      become significant. CONCLUSIONS: Traffic exposure was associated with decreased
      lung function in adults with asthma.

PMID- 19152969
TI  - High-titer IgE antibody specific for pollen allergens in northern California is
      associated with both wheezing and total serum IgE.

PMID- 19152970
TI  - Pathogenicity of IgE in autoimmunity: successful treatment of bullous pemphigoid
      with omalizumab.

PMID- 19152971
TI  - Neuronal gene delivery by negatively charged pullulan-spermine/DNA anioplexes.
AB  - Nonviral gene transfer to neurons remains unreliable due to a lack of effective
      and nontoxic vectors. Here, we achieved effective neuronal gene delivery through
      salt-free complexation of plasmid DNA and pullulan-spermine, a conjugate prepared
      from a naturally derived polysaccharide and polyamine. Specifically, at low
      spermine nitrogen:DNA phosphate (N:P) ratios, complexes formed with zeta
      potential and diameter of approximately-40mV and 350nm, respectively. Higher N:P
      ratios increased the zeta-potential to approximately +10mV. All complexes were
      stable for at least 1 week and protected DNA from degradation. In vitro
      transfection of rat sensory neurons occurred at all N:P ratios, but uniquely,
      efficiency was highest for anionic complexes (anioplexes). Subsequent analyses
      revealed the inhibition of reporter gene expression by asialofetuin (1mg/ml) and
      methyl-beta-cyclodextrin (5mm), indicating utilization of glycoprotein-specific
      interactions and lipid rafts for uptake and intracellular trafficking. In marked
      contrast to a commercial cationic lipid reagent, anioplexes did not exhibit
      measurable cytotoxicity at up to 20microg/ml DNA. Additionally, transfection
      efficiency was maintained in the presence of serum and antibiotics. Based on
      these favorable properties, we successfully established two transfection methods
      for cultured adult sensory neurons and tissue explants. Collectively, these data
      suggest that negatively charged pullulan-spermine/DNA anioplexes could represent
      an effective gene delivery technology, particularly for neurons.

PMID- 19152972
TI  - The influence of the sequential delivery of angiogenic factors from affinity
      binding alginate scaffolds on vascularization.
AB  - This study describes the features of tissue-engineering scaffold capable of
      sequentially delivering three angiogenic factors. The scaffold consists of
      alginate-sulfate/alginate, wherein vascular endothelial growth factor (VEGF)
      platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta1
      (TGF-beta1) are bound to alginate-sulfate with an affinity similar to that
      realized upon their binding to heparin. Factor release rate from the scaffold was
      correlated with the equilibrium binding constants of the factors to the matrix,
      thus enabling the sequential delivery of VEGF, PDGF-BB and TGF-beta1. In alginate
      scaffolds lacking alginate-sulfate, release of the adsorbed proteins was
      instantaneous. After subcutaneous implantation for 1 and 3 months in rats, the
      blood vessel density and percentage of mature vessels were 3-fold greater in the
      triple factor-bound scaffolds than in the factor-adsorbed or untreated scaffolds.
      Moreover, vascularization within the triple factor-bound scaffolds was superior
      to that found in scaffolds delivering only basic fibroblast growth factor.
      Application of this novel scaffold may be extended to the combined delivery of
      additional heparin-binding angiogenic factors or combinations of growth factors
      active in different tissue regeneration processes.

PMID- 19152973
TI  - The control of anchorage-dependent cell behavior within a hydrogel/microcarrier
      system in an osteogenic model.
AB  - The use of injectable hydrogels for tissue engineering purposes such as bone
      regeneration has been hampered by the mass depletion of cells after
      encapsulation, due to the lack of a proper interface between hydrogel matrices
      and osteo-progenitor cells. Efforts to graft bioactive molecules as cell
      attachment moieties have achieved limited success. In this study, we devised a
      solution to promote cellular focal adhesion within hydrogels, and elicit the
      mechanism behind cellular survival/death therein. We found that the fulfillment
      of ligation between cellular integrins and extracellular ligands, instead of the
      expression of integrins per se, is essential to avoid apoptosis in gel
      encapsulated anchorage-dependent cells (ADCs). Absence of such ligation brought
      about mass cell death in our osteogenic model with osteoblasts (as representative
      of ADCs) and failure of osteogenic commitment of mesenchymal stem cells (as
      representative of anchorage-dependent progenitors). We have designed a gel-based
      composite system that works as a suspension of injectable cell-laden
      microcarriers in hydrogel, as compared to the conventional cell-suspended
      hydrogels. Injectable microscopic anchors (microcarriers) not only provide
      platforms for cellular focal adhesion but also facilitate the cells to overcome
      gel enlacement and fully spread out into their natural morphology. Further in
      vitro and in vivo osteogenic investigations show the composites to be a competent
      potential injectable vehicle for the conveyance of ADCs and regenerations of bone
      and other tissues.

PMID- 19152974
TI  - Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue
      engineering.
AB  - Mimicking certain features (e.g. nanoscale topography and biological cues) of
      natural extracellular matrix (ECM) is advantageous for the successful
      regeneration of damaged tissue. In this study, nanofibrous gelatin/apatite (NF
      gelatin/apatite) composite scaffolds have been fabricated to mimic both the
      physical architecture and chemical composition of natural bone ECM. A thermally
      induced phase separation (TIPS) technique was developed to prepare nanofibrous
      gelatin (NF-gelatin) matrix. The NF-gelatin matrix mimicked natural collagen
      fibers and had an average fiber diameter of about 150nm. By integrating the TIPS
      method with porogen leaching, three-dimensional NF-gelatin scaffolds with well
      defined macropores were fabricated. In comparison to Gelfoam (a commercial
      gelatin foam) with similar pore size and porosity, the NF-gelatin scaffolds
      exhibited a much higher surface area and mechanical strength. The surface area
      and compressive modulus of NF-gelatin scaffolds were more than 700 times and 10
      times higher than that of Gelfoam, respectively. The NF-gelatin scaffolds also
      showed excellent biocompatibility and mechanical stability. To further enhance
      pre-osteoblast cell differentiation as well as improving mechanical strength,
      bone-like apatite particles (<2microm) were incorporated onto the surface of NF
      gelatin scaffolds via a simulated body fluid (SBF) incubation process. The NF
      gelatin/apatite scaffolds 5 days after SBF treatment showed significantly higher
      mechanical strength than NF-gelatin scaffolds 5 days after SBF treatment.
      Furthermore, the incorporated apatite in the NF-gelatin/apatite composite
      scaffold enhanced the osteogenic differentiation. The expression of BSP and OCN
      in the osteoblast-(NF-gelatin/apatite composite) constructs was about 5 times and
      2 times higher than in the osteoblast-(NF-gelatin) constructs 4 weeks after cell
      culture. The biomimetic NF-gelatin/apatite scaffolds are, therefore, excellent
      for bone tissue engineering.

PMID- 19152975
TI  - The role of doxorubicin in non-viral gene transfer in the lung.
AB  - Proteasome inhibitors have been shown to increase adeno-associated virus (AAV)
      mediated transduction in vitro and in vivo. To assess if proteasome inhibitors
      also increase lipid-mediated gene transfer with relevance to cystic fibrosis
      (CF), we first assessed the effects of doxorubicin and N-acetyl-l-leucinyl-l
      leucinal-l-norleucinal in non-CF (A549) and CF (CFTE29o-) airway epithelial cell
      lines. CFTE29o- cells did not show a response to Dox or LLnL; however, gene
      transfer in A549 cells increased in a dose-related fashion (p < 0.05), up to
      approximately 20-fold respectively at the optimal dose (no treatment: 9.3 x 10(4)
      +/- 1.5 x 10(3), Dox: 1.6 x 10(6)+/-2.6 x 10(5), LLnL: 1.9 x 10(6) +/- 3.2 x
      10(5)RLU/mg protein). As Dox is used clinically in cancer chemotherapy we next
      assessed the effect of this drug on non-viral lung gene transfer in vivo. CF
      knockout mice were injected intraperitoneally (IP) with Dox (25-100 mg/kg)
      immediately before nebulisation with plasmid DNA carrying a luciferase reporter
      gene under the control of a CMV promoter/enhancer (pCIKLux) complexed to the
      cationic lipid GL67A. Dox also significantly (p < 0.05) increased expression of a
      plasmid regulated by an elongation factor 1alpha promoter (hCEFI) approximately 8
      fold. Although administration of Dox before lung gene transfer may not be a
      clinically viable option, understanding how Dox increases lung gene expression
      may help to shed light on intracellular bottle-necks to gene transfer, and may
      help to identify other adjuncts that may be more appropriate for use in man.

PMID- 19152977
TI  - T cell function in chronic myeloid leukemia and its treatment with tyrosine
      kinase inhibitors--clues from and for sarcoidosis.

PMID- 19152978
TI  - All-distance visual acuity and contrast visual acuity in eyes with a refractive
      multifocal intraocular lens with minimal added power.
AB  - PURPOSE: To compare visual acuity (VA) from far to near distances, photopic and
      mesopic contrast VA, and contrast VA in the presence of a glare source (glare
      VA), between eyes with a new refractive multifocal intraocular lens (IOL) with
      added power of only +3.0 diopters and those with a monofocal IOL. DESIGN:
      Comparative, nonrandomized, interventional study. PARTICIPANTS: Forty-four eyes
      of 22 patients who were scheduled for implantation of a refractive multifocal IOL
      (Hoya SFX MV1; Tokyo, Japan) and 44 eyes of 22 patients scheduled for
      implantation of a monofocal IOL. INTERVENTION: All patients underwent
      phacoemulsification with bilateral implantation of either multifocal or monofocal
      IOLs. MAIN OUTCOME MEASURES: At approximately 3 months after surgery, monocular
      and binocular VA from far to near distances was measured using the all-distance
      vision tester (Kowa AS-15; Tokyo, Japan), whereas photopic and mesopic contrast
      VA and glare VA were examined using the Contrast Sensitivity Accurate Tester
      (Menicon CAT-2000, Nagoya, Japan). Pupillary diameter and the degree of IOL
      decentration and tilt were correlated with VA at all distances. RESULTS: Mean VA
      in both the multifocal and monofocal IOL groups decreased gradually from far to
      near distances. When comparing the 2 groups, however, both uncorrected and best
      distance-corrected intermediate VA at 0.5 m and near VA at 0.3 m in the
      multifocal IOL group were significantly better than those in the monofocal IOL
      group (P<or=0.0037), although there was no significant difference in far VA or in
      intermediate VA at 0.7 and 1.0 m. Photopic and mesopic contrast VA and glare VA
      were similar between the 2 groups. In both the multifocal and monofocal IOL
      groups, no significant correlation was found between VA at any distance and
      pupillary diameter or between VA and the degree of IOL decentration and tilt.
      CONCLUSIONS: A new refractive multifocal IOL with minimal added power provides
      significantly better intermediate and near VA than does a monofocal IOL; contrast
      VA and glare VA are not impaired with this multifocal IOL. Visual acuity at all
      distances with this IOL is not correlated with pupillary diameter or with IOL
      decentration and tilt.

PMID- 19152976
TI  - Connective tissue and related disorders and preterm birth: clues to genes
      contributing to prematurity.
AB  - To identify candidate genes contributing to preterm birth, we examined the
      existing literature on the association between known disorders of connective
      tissue synthesis and metabolism and related diseases and prematurity. Our
      hypothesis was that abnormal matrix metabolism contributes to prematurity by
      increasing risk of preterm premature rupture of membranes (PPROM) and cervical
      incompetence. Based on this review, we identified gene mutations inherited by the
      fetus that could predispose to preterm birth as a result of PPROM. The
      responsible genes include COL5A1, COL5A2, COL3A1, COL1A1, COL1A2, TNXB, PLOD1,
      ADAMTS2, CRTAP, LEPRE1 and ZMPSTE24. Marfan syndrome, caused by FBN1 mutations,
      and polymorphisms in the COL1A1 and TGFB1 genes have been associated with
      cervical incompetence. We speculate that an analysis of sequence variation at the
      loci noted above will reveal polymorphisms that may contribute to susceptibility
      to PPROM and cervical incompetence in the general population.

PMID- 19152979
TI  - Emergence of community-associated methicillin-resistant Staphylococcus aureus (CA
      MRSA) in Southeast Austria.

PMID- 19152980
TI  - Recommendations for the prevention of secondary Haemophilus influenzae type b
      (Hib) disease.
AB  - Haemophilus influenzae serotype b (Hib) can cause severe life threatening disease
      in healthy individuals, with over 80% of cases in the pre-vaccine era occurring
      in children under five years of age. The introduction of Hib conjugate vaccine
      into routine childhood immunisation programmes has resulted in a dramatic
      reduction in the incidence of invasive Hib disease across all age groups. The
      objective of this paper is to update existing UK guidelines on the prevention of
      Hib disease among contacts of an index case by reviewing the original literature
      and the current epidemiology of Hib carriage and invasive disease. Household
      contacts of individuals who develop invasive Hib disease are at higher risk of
      developing secondary Hib infection themselves, particularly if the contact is a
      young child or is immunosuppressed. Pre-school contacts of young children with
      invasive Hib disease are also at higher risk of developing secondary Hib
      infection. Rifampicin at a dose of 20mg/kg/day for 4 days is highly effective in
      eradicating pharyngeal carriage of Hib and reducing the risk of invasive Hib
      disease among household and pre-school contacts. Children under 10 years of age
      who develop invasive Hib disease should also receive rifampicin chemoprophylaxis
      to eliminate carriage and have Hib antibody levels tested around four weeks after
      infection. Hib vaccine failure cases should additionally have immunoglobulin
      concentrations measured and be assessed for evidence of an immune deficiency. If
      there is a vulnerable individual (child younger than 10 years or an
      immunosuppressed or asplenic individual of any age) among the household contacts
      of a case, all members of that household, including the index case, should
      receive chemoprophylaxis. All children younger than 10 years in the household
      should be appropriately vaccinated against Hib. Where more than one case occurs
      in a pre-school or primary school setting, chemoprophylaxis should be offered to
      all room contacts (including staff), and unimmunised and partially immunised
      children younger than 10 years should complete their primary immunisations,
      including a booster dose, as soon as possible. Families of children attending the
      same pre-school or primary school as an index case should be advised to seek
      medical advice if their child becomes unwell.

PMID- 19152981
TI  - Fate and effects of octylphenol in a Microcystis aeruginosa culture medium.
AB  - Octylphenol (OP) is a xenobiotic with endocrine disrupting properties found in
      freshwaters worldwide. Its effects have been studied in organisms with nuclear
      receptors but effects on phytoplankton communities are poorly characterized,
      despite the fact that these organisms are constantly exposed to this compound.
      For this reason fate and effects of OP in the cyanobacterium Microcystis
      aeruginosa were assessed from 10 nM to 5 microM OP concentration. Up to a test
      concentration of 250 nM, OP removal increased significantly in the presence of
      cyanobacteria, the compound half-life in the absence of cells being 15 days
      against 9 days in the presence of the cells. Only 4% of the total OP removed was
      found bound to the cells, indicating an active metabolization of the compound.
      Moreover, the role of the exudates produced by M. aeruginosa, in the OP removal
      from culture medium, was assessed. Culture medium with exudates, resulting from a
      7-day growth of M. aeruginosa, spiked with 50 nM OP, showed a higher half-life
      (22 days). Compared to culture medium without exudates, it can be hypothesized
      that higher organic matter concentrations make the hydrolysis or photolysis of OP
      more difficult. In culture media, the cells of M. aeruginosa could compensate and
      even counteract this, as OP half-life was shortened. At higher OP levels (1.25
      and 5 microM) M. aeruginosa growth was impaired, indicating toxic effects. This
      shortage of biomass prevented the M. aeruginosa-assisted OP withdrawal from the
      culture media.

PMID- 19152982
TI  - Genetic variability of hepatitis B virus and response to antiviral treatments:
      searching for a bigger picture.

PMID- 19152983
TI  - Moving on a roundabout at the end of life-What counts? Waiting times for transfer
      to sheltered accommodation for older people in Sweden.
AB  - In Sweden, increased care in ordinary housing has contributed to a reduction of
      rooms in sheltered accommodation. The allocation of rooms has become stricter.
      Only those whose care needs cannot be met in any other ways are allocated such
      accommodation. The aim was to explore the waiting time between the transfer
      decision and the accomplishment of the move from the initial form of care to
      sheltered accommodation as well as whether there were differences in waiting time
      in relation to certain demographic data. METHOD: 445 decision documents were
      analysed. Mean and 95% confidence intervals (CI) for waiting time and date of the
      move to sheltered accommodation were calculated. Differences between mean age and
      waiting time were analysed using Student's T-test. Effects of age, gender and
      cohabitation on waiting time were estimated by means of multifactor linear
      regression. RESULTS: The main finding was that the difference in mean waiting
      time was shortest when moving from hospital, irrespective of destination. There
      were no significant differences in waiting time in relation to gender, age or
      cohabitation. CONCLUSION: The reason for a move was often described by means of
      abstract standard formulations. There is a need for standardised models and
      assessment instruments in order to ensure older people's safety and to compare
      different forms of accommodation.

PMID- 19152984
TI  - Effect of gefitinib on N-nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone induced lung tumorigenesis in A/J mice.
AB  - Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR
      TKI). N-Nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a
      potent carcinogen found in tobacco smoke, induces lung tumors in A/J mice. NNK
      induces cellular transformation resulting in the over-expression of EGFR.
      Accordingly, EGFR may be a target for cancer prevention. In this study, we
      investigated the effect of gefitinib on NNK-induced tumorigenesis and the
      carcinogenicity of gefitinib in A/J mice. A total of 180 four-week-old female A/J
      mice were randomly divided into six groups: group 1 (controls), treated with
      deionized water; group 2, treated with 5 mg/kg p.o. gefitinib; group 3, treated
      with 50 mg/kg p.o. gefitinib (to test the carcinogenicity of gefitinib); group 4
      (controls for NNK treatment), treated with deionized water; group 5, treated with
      5 mg/kg p.o. gefitinib; and group 6, treated with 50 mg/kg p.o. gefitinib and
      injected with NNK once at 8 weeks of age to test the chemopreventive activity of
      gefitinib. Gefitinib was given once a day, 5 days a week by gavage, beginning at
      4 weeks of age and continuing for 26 weeks. All mice were sacrificed at 30 weeks
      of age. The multiplicities of the NNK-induced lung tumors were significantly
      suppressed in a dose-dependent manner. Gefitinib had no effect on body weight at
      a low dose. The administration of gefitinib alone for 26 weeks did not induce
      tumorigenesis; instead, it significantly suppressed the incidence of spontaneous
      tumors in the mice, in contrast with other anti-cancer agents. Gefitinib did not
      induce lung fibrosis when compared with control mice by Azan-Mallory staining.
      Our results suggest that gefitinib has a weak but significant chemopreventive
      effect with no carcinogenicity or pulmonary toxicity in A/J mice.

PMID- 19152985
TI  - HCMV infection of PDCs deviates the NK cell response into cytokine-producing
      cells unable to perform cytotoxicity.
AB  - Plasmacytoid dendritic cells (PDCs) are thought to induce natural killer (NK)
      cell CD69 expression, cytotoxicity, and cytokine secretion. Since human
      cytomegalovirus (HCMV) interferes with multiple functions of infected cells, we
      investigated whether the HCMV infection of PDCs affects NK cell activation. Human
      PDCs infected with HCMV strain VR1814 at multiplicity of infection (MOI) 10 or
      stimulated with control CpG-A were cocultured with human NK cells in an
      autologous system. As expected, CpG-stimulation of PDCs increased expression of
      the NK cell activation marker CD69, enhanced cytotoxicity and stimulated
      secretion of tumor necrosis factor (TNF)-alpha and IFN-alpha, but not IFN-gamma,
      and induced NK cell migration. In contrast, incubation with HCMV-infected PDCs
      induced CD69 expression, migration and elevated production of both TNF-alpha and
      IFN-gamma by NK cells, but these cells did not exhibit enhanced cytotoxicity.
      Also, HCMV-infected PDCs were unable to induce increased intracellular perforin
      levels. Thus, HCMV infection of PDCs induce NK cells to increase CD69 expression
      and produce inflammatory cytokines, but infected PDCs are unable to induce NK
      cell cytotoxicity. This NK cell phenotype with impaired killing abilities, but
      enhanced production of inflammatory cytokines may instead facilitate reactivation
      and replication of HCMV. This data indicate that HCMV can target PDCs through
      novel dual strategies that may result in evasion of the innate immune response at
      the same time as facilitating virus reactivation and replication early in the
      infection, through enhanced inflammation.

PMID- 19152986
TI  - Selective noradrenergic vulnerability in alpha-synuclein transgenic mice.
AB  - Classical pathological signs of Parkinson's disease (PD) include loss of
      dopaminergic neurons in substantia nigra (SN) and noradrenergic neurons in locus
      coeruleus (LC), and deposition of Lewy bodies rich in the presynaptic protein
      alpha-synuclein (ASYN). Mammalian genetic models based on ASYN overexpression,
      however, have generally not reproduced the profound dopaminergic deficit of PD
      and do not display classical PD phenotypes. In the current study we examined
      these catecholaminergic systems in transgenic (Tg) mice expressing the A53T
      mutant of human ASYN under the Prion promoter. Surprisingly we detected a
      substantial reduction in norepinephrine (NE), but not dopamine (DA), levels in
      spinal cord, olfactory bulb and striatum of aged (15-month-old), but not young (4
      month-old) transgenic compared to control mice. In spinal cord and olfactory bulb
      of 15-month-old Tg mice there was an age-dependent decrease in tyrosine
      hydroxylase (TH) protein levels, which in spinal cord was accompanied by a
      decrease in TH-positive terminals detected by immunohistochemistry. There was no
      difference in the number of TH-positive neuron cell bodies in SN or LC between Tg
      and control mice. We conclude that aberrant ASYN, expressed in both SN and LC,
      induces preferential degeneration of noradrenergic terminals. These observations
      suggest that in mice the NE may be more vulnerable than the DA system to the
      toxic effects of aberrant alpha-synuclein, and are in line with the major damage
      to the NE system that occurs in patients with PD.

PMID- 19152987
TI  - Synthesis and evaluation of antibacterial activities of andrographolide
      analogues.
AB  - Andrographolide (Andro), the main active component of the herb Andrographis
      paniculata, has been used for many years to treat a variety of diseases including
      bacterial and viral infections. Andro was recently reported to act by inhibiting
      the bacterial quorum sensing system. We have synthesized several Andro analogues
      and investigated their antibacterial activity and mechanism of action. The new
      compounds were found to be much more potent than the parent Andro in inhibiting
      bacterial growth and quorum sensing system. Compounds 5 and 7 significantly
      reduced virulence factor production. Compound 7 completely inhibited Pseudomonas
      aeruginosa (P. aeruginosa) biofilm formation, and exhibited synergistic activity
      with conventional antibiotics. These findings suggest that compound 7 may be the
      basis for future drug development to combat the unmet needs of virulence factor
      production, biofilm formation and antibiotic resistance.

PMID- 19152988
TI  - Perceiving and practicing the nature of nursing in Poland.
AB  - INTRODUCTION: The social and political transition taking place in Poland during
      the last decade has resulted in changes in the system of education. The results
      of empirical studies indicate that both the system of education and the period of
      its transition exerted an influence on the qualifications of nurses. AIM: The
      focus of the study was the relationship between the selected education factors
      and the occupational experience of nurses. METHODS: The study was conducted by
      the method of a diagnostic survey with the use of the authors' version of a
      questionnaire form. The variables were tested by means of chi-square test and
      Spearman's correlation test. The investigations covered a group of 324
      occupationally active nurses in area of the city of Lublin. CONCLUSIONS: The
      analysis indicates that among many variables concerning education and
      occupational improvement, only the type of education (1st and 2nd level of
      occupational differentiation) has a statistically significant effect on auto
      defining of nursing in the the nature of occupational activities performed.

PMID- 19152989
TI  - Negotiating credibility: first-time mothers' experiences of contact with the
      labour ward before hospitalisation.
AB  - OBJECTIVE: to explore Norwegian nulliparous women's experiences of communication
      and contact with midwives at the labour ward in the early phase of labour.
      DESIGN: a qualitative study based on in-depth interviews. PARTICIPANTS: 17 women
      expecting their first baby. FINDINGS: four themes that emerged in the collected
      material seem to be central to how the labouring women decided to make contact
      with the labour ward and how they experienced this contact with the staff: (a)
      negotiating on two fronts, (b) avoiding being sent home, (c) searching for
      regularity, and (d) experiencing vulnerability. CONCLUSIONS: the study shows how
      women in labour for the first time negotiate their credibility with midwives
      through the requisite pattern of regularity, and also shows their vulnerability
      in attempting to avoid being sent home from hospital because it is 'too soon' to
      be admitted. It also argues that the midwifery profession is ambivalent about the
      paradigm to which it conforms in its contact with women in early labour.
      IMPLICATIONS FOR PRACTICE: the findings of this study show that the way in which
      questions are asked in this phase is very important. Midwives should be aware
      that if they only ask the 'standard question' related to the pattern of
      contraction regularity, they might lose vital information and also deprive the
      woman of the chance to verbalise her experiences and her needs as she perceives
      them. If the focus is shifted from the rigid instructions that women are given to
      an emphasis on the women's actual experiences, the need for negotiation will
      probably diminish. The task of assessing and evaluating women in early labour
      need not necessarily be performed inside the ordinary labour ward, but may be
      done in a more home-like environment outside the hospital or in the woman's home.

PMID- 19152990
TI  - Ion activity and distribution of heavy metals in acid mine drainage polluted
      subtropical soils.
AB  - The oxidative dissolution of mine wastes gives rise to acidic, metal-enriched
      mine drainage (AMD) and has typically posed an additional risk to the
      environment. The poly-metallic mine Dabaoshan in South China is an excellent test
      site to understand the processes affecting the surrounding polluted agricultural
      fields. Our objectives were firstly to investigate metal ion activity in soil
      solution, distribution in solid constituents, and spatial distribution in
      samples, secondly to determine dominant environment factors controlling metal
      activity in the long-term AMD-polluted subtropical soils. Soil Column Donnan
      Membrane Technology (SC-DMT) combined with sequential extraction shows that
      unusually large proportion of the metal ions are present as free ion in the soil
      solutions. The narrow range of low pH values prevents any pH effects during the
      binding onto oxides or organic matter. The differences in speciation of the soil
      solutions may explain the different soil degradation observed between paddy and
      non-paddy soils.

PMID- 19152991
TI  - The emergence of global health partnerships as facilitators of access to
      medication in Africa: a narrative policy analysis.
AB  - Over the last decade global health partnerships (GHPs) have been formed to
      provide a better policy response to Africa's health problems. This paper uses
      narrative policy analysis to explain the historical processes and challenges
      facing national and global health policy in facilitating access to medication in
      African countries. An overview of the historical context of events leading to the
      creation of GHPs is followed by a content and context analysis of two GHPs - Roll
      Back Malaria partnership and the Accelerating Access Initiative. The historical
      narratives implicitly reflect the context in which policy decisions are produced
      and implemented. The deployment of GHPs in Africa reflects a convergence of the
      competing and conflicting narratives, in relating to strategies previously
      promoted by various multilateral and bilateral development agencies,
      international civil society organizations, and the private commercial industry to
      facilitate access to medication.

PMID- 19152992
TI  - Barriers and facilitators related to mammography use among lower educated Mexican
      women in the USA.
AB  - This study explores barriers to and facilitators of breast cancer screening and
      how people in a woman's social network influence these screening behaviors. A
      total of 40 semi-structured qualitative interviews were conducted in rural
      Washington State (USA) among Mexican women aged 50 and over. Eligible women
      reported either having had a mammogram within the last two years, over two years
      ago, or never. We found that lack of health insurance, the perception that the
      mammogram is painful, and fear of finding cancer were cited as barriers to
      participation in mammography screening. Women who had lived in the US for a
      shorter period were more likely to report never having had a mammogram than women
      who had lived in the US for a longer period. Women often cited daughters and
      female friends as those from whom they received advice or encouragement to
      receive a mammogram. Few differences were found related to network size and
      mammography use among the groups. These findings may be useful in designing
      interventions to promote mammography use. Including daughters in intervention
      activities may help facilitate mammography use among Mexican women.

PMID- 19152994
TI  - Counter design influences the privacy of patients in health care.
AB  - A re-furnishing of counter areas in primary health care was used to assess
      patient privacy and its influences on the nature of conversations in a controlled
      experiment. Patients in two community-based pharmacies in the Netherlands were
      assigned to enclosed counters and a queue at distance, or to counters that
      exposed patients mutually and a closer queue. Patients assigned to counters with
      reduced sight were more satisfied with the privacy than patients at visually
      exposed counters. However, in comparison with visually exposed pharmacy counters,
      conversations of patients at enclosed counters could still be overheard and did
      not have different conversations to other patients. Architectural design of
      health-care institutions has potential to positively influence perceived patient
      privacy in areas in where multiple patient-staff communications routinely occur
      and where patient privacy is an important issue, but enclosed counters with a
      queue at distance do not prevent incidental disclosure of individually
      identifiable health information.

PMID- 19152993
TI  - Early origins of health disparities: burden of infection, health, and
      socioeconomic status in U.S. children.
AB  - Recent work in biodemography has suggested that lifetime exposure to infection
      and inflammation may be an important determinant of later-life morbidity and
      mortality. Early exposure to infections during critical periods can predispose
      individuals to chronic disease, in part through the reallocation of energy away
      from development needed for immune and inflammatory responses. Furthermore,
      markers of inflammation are known to vary by socioeconomic status in adults and
      may contribute to overall socioeconomic health inequalities, but little is known
      about how the sources of this inflammation differ over the life course. This
      paper uses novel biomarker data from the Third National Health and Nutrition
      Examination Survey (NHANES III) to test the association of the burden of common
      chronic infections (Helicobacter pylori (H. pylori), cytomegalovirus (CMV),
      herpes simplex virus-1 (HSV-1), hepatitis A and hepatitis B) with height-for-age
      and asthma/chronic respiratory conditions in U.S. children ages 6 and older, and
      the association of these chronic infections to children's socioeconomic status. A
      higher burden of infection is found to be associated with lower height-for-age as
      well as an increased likelihood of asthma net of race/ethnicity, family income,
      and parental education. Children with lower family income, lower parental
      education, and non-white race/ethnicity have a higher likelihood of infection
      with several individual pathogens as well as the overall burden of infection.
      Differential exposure and/or susceptibility to infections may be one mechanism
      through which early social factors get embodied and shape later-life health
      outcomes.

PMID- 19152995
TI  - The relational underpinnings of quality internal auditing in medical clinics in
      Israel.
AB  - Internal auditing is a key mechanism in enhancing organizational reliability.
      However, research on the ways quality internal auditing is enabled through
      learning, deterrence, motivation and process improvement is scant. In particular,
      the relational underpinnings of internal auditing have been understudied. This
      study attempts to address this need by examining how organizational trust,
      perceived organizational support and psychological safety enable internal
      auditing. Data collected from employees in medical clinics of one of the largest
      healthcare organizations in Israel at two points in time six months apart. Our
      results show that organizational trust and perceived organizational support are
      positively related to psychological safety (measured at time 1), which, in turn,
      is associated with internal auditing (measured at time 2).

PMID- 19152996
TI  - Experimental assessment of calvarial bone defect re-ossification stimulation
      using low-intensity pulsed ultrasound.
AB  - Ultrasound treatment has been proposed by several authors to enhance the repair
      of long bone injury. The present study investigated in a murine model the
      treatment by low-intensity pulsed ultrasound (LIPUS) of calvarial flat bone
      defect. The animals were operated to create bone defect and exposed to ultrasound
      for 5 min per day, 5 d per week, during two weeks. Two intensities of ultrasound
      (1 MHz, 100 Hz pulse repetition frequency and 20% duty cycle) were investigated:
      100 and 300 mW/cm(2) spatial-averaged, time-averaged. Re-ossification surface and
      volume were determined after 30 and 60 days using computerized X-ray tomography
      in all animals of the control and treated groups. The results showed a
      significant increase of bone re-ossification in the group treated with the higher
      intensity ultrasound (mean value of 18% volume reconstruction), whereas lower
      bone reconstruction was observed in the lower-intensity and control groups
      (respective mean values of 10 and 12% volume reconstruction).

PMID- 19152997
TI  - Contrast biases the autocorrelation phase shift estimation in Doppler tissue
      imaging.
AB  - Quantitative assessment of regional myocardial function at rest and during stress
      with Doppler tissue imaging (DTI) plays an important role in daily routine
      echocardiography. However, reliable visual analysis is largely dependent on image
      quality and adequate border delineation, which still remains a challenge in a
      significant number of patients. In this respect, an ultrasound contrast agent
      (UCA) is often used to improve visualization in patients with suboptimal image
      quality. The knowledge of how DTI measurements will be affected by UCA present in
      the tissue is therefore of significant importance for an accurate interpretation
      of local myocardial motion. The aim of this paper was to investigate how signal
      contribution from UCA and nonlinear wave propagation influence the performance of
      the autocorrelation phase shift estimator used for DTI applications. Our results
      are based on model experiments with a clinical 2-D grayscale scanner and
      computational simulations of the DTI velocity estimator for synthetically-derived
      pulses, simulated bubble echoes and experimentally-sampled RF data of transmitted
      pulses and backscattered contrast echoes. The results show that destruction of
      UCA present in the tissue will give rise to an apparent bidirectional velocity
      bias of individual velocity estimates, but that spatial averaging of individual
      velocity measurements within a region-of-interest will result in a negative bias
      (away from the transducer) of the estimated mean or mean peak velocity. The UCA
      destruction will also have a significant impact on the measured integrated mean
      velocity over time, i.e., displacement. To achieve improved visualization with
      UCA during DTI-examinations, we either recommend that it is performed at low
      acoustic powers, mechanical index <or=0.3, thereby minimizing the effects from
      bubble rupture, or that each Doppler pulse package is preceded by a destruction
      burst similar to "Flash imaging" to clear the target area of contrast
      microbubbles.

PMID- 19152999
TI  - Statistical region-based segmentation of ultrasound images.
AB  - Segmentation of ultrasound images is a challenging problem due to speckle, which
      corrupts the image and can result in weak or missing image boundaries, poor
      signal to noise ratio and diminished contrast resolution. Speckle is a random
      interference pattern that is characterized by an asymmetric distribution as well
      as significant spatial correlation. These attributes of speckle are challenging
      to model in a segmentation approach, so many previous ultrasound segmentation
      methods simplify the problem by assuming that the speckle is white and/or
      Gaussian distributed. Unlike these methods, in this article we present an
      ultrasound-specific segmentation approach that addresses both the spatial
      correlation of the data as well as its intensity distribution. We first
      decorrelate the image and then apply a region-based active contour whose motion
      is derived from an appropriate parametric distribution for maximum likelihood
      image segmentation. We consider zero-mean complex Gaussian, Rayleigh, and Fisher
      Tippett flows, which are designed to model fully formed speckle in the in
      phase/quadrature (IQ), envelope detected, and display (log compressed) images,
      respectively. We present experimental results demonstrating the effectiveness of
      our method and compare the results with other parametric and nonparametric active
      contours.

PMID- 19152998
TI  - Glomerular capillary hemorrhage induced in rats by diagnostic ultrasound with gas
      body contrast agent produces intratubular obstruction.
AB  - Glomerular capillary hemorrhage (GCH) induced by ultrasonic cavitation during
      diagnostic imaging represents a unique contrast agent-related nephron injury.
      Consequences of GCH during 1.5-MHz diagnostic ultrasound with contrast agent were
      examined by histologic methods in rats. Definity was infused at 10 microl/kg/min
      for 5 min at the start of 8 min of intermittent image-exposure, with 2.3 MPa in
      situ peak rarefactional pressure amplitude. Kidney samples were taken for
      histology at 5 min, 30 min, 4 h, 2 d, 1 week and 4 weeks post exposure. In
      addition, samples were taken at 4 h from groups treated with heparin or
      aminocaproic acid. GCH was found in 61% of glomeruli in the center of the scan
      plane 5 min after exposure, which declined (p < 0.05) to 36.3% after 4 h. The
      width of Bowman's space was significantly increased for glomeruli with GCH
      relative to glomeruli without GCH (p < 0.05), consistent with tubular
      obstruction. Antibody staining revealed fibrin clotting in Bowman's space in 4-h
      samples and this persisted in the 2-d samples. Heparin reduced and aminocaproic
      acid increased the GCH seen in 4-h samples. Tubular dilation was evident with
      injury to the epithelium after 2 d. After one week, areas of inflammatory cell
      infiltration were present. After four weeks, areas of interstitial fibrosis were
      revealed by Masson's trichrome stain. The consequences of GCH induced by
      diagnostic ultrasound with contrast agents include rupture of glomerular
      capillaries, procoagulant activity resulting in intratubular obstruction, and the
      potential for progression of the resulting tubular injury toward interstitial
      fibrosis.

PMID- 19153000
TI  - Measurement of the dispersion and attenuation of cylindrical ultrasonic guided
      waves in long bone.
AB  - Osteoporotic bones are likely to have less cortical bone than healthy bones. The
      velocities of guided waves propagating in a long cylindrical bone are very
      sensitive to bone properties and cortical thickness (CTh). This work studies the
      dispersion and attenuation of ultrasonic guided waves propagating in long
      cylindrical bone. A hollow cylinder filled with a viscous liquid was used to
      model the long bone and then to calculate the theoretical phase and group
      velocities, as well as the attenuation of the waves. The generation and selection
      of guided wave modes were based on theoretical dispersive curves. The phase
      velocity and attenuation of cylindrical guided wave modes, such as L(0,1), L(0,2)
      and L(0,3), were measured in bovine tibia using angled beam transducers at
      various propagation distances ranging from 75 to 160 mm. The results showed that
      the phase velocity of the L(0,2) guided wave mode decreased with an increase in
      CTh. The attenuation of the low cylindrical guided wave modes was a nonlinear
      function that increased with propagation distance and mode order. The L(0,2) mode
      had a different attenuation for each CTh. The experimental results were in good
      agreement with the predicted values. Cylindrical guided waves of low-frequency
      and low-order have been shown to demonstrate more dispersion and less attenuation
      and should, therefore, be used to evaluate long bone.

PMID- 19153002
TI  - The effect of mineral carrier composition on phosphate-accumulating bacteria
      immobilization.
AB  - The goal of this study was to determine the dynamics and yield of immobilization
      of the phosphate-accumulating bacterium Acinetobacter junii on mineral carriers.
      As mineral carriers natural clinoptilolite tuff from Turkey (T) and Serbia (S)
      and natural bentonite (TER), in original and magnesium (Mg)-exchanged form were
      used. The key feature which determined the extent of immobilization of A. junii
      was the type of carrier; the immobilization yield decreased in order T>TER>S. The
      number of immobilized cells was significantly higher for the Mg-exchanged
      carriers when compared to their original counterparts (95 and 75 x 10(8)CFU g(-1)
      for T, 74 and 58 x 10(8)CFU g(-1) for TER, 19 and 6 x 10(8)CFU g(-1) for S). The
      Mg-exchanged T and S displayed a prolonged biofilm growth up to 24h, while the
      original counterparts reached the mature biofilm after 12h of incubation. Both
      forms of TER reached the mature biofilm after 24h of incubation, due to swelling
      property of the material. The number of immobilized cells correlated
      significantly negatively with particle size of the carrier, indicating that
      particle size is another important feature which determined the extent of
      immobilization. The Mg-exchange of original carriers resulted in significant
      increase of the zeta potential. When all of the materials were compared, the
      increase of the zeta potential of carriers correlated negatively with the number
      of immobilized cells, suggesting that the zeta potential of material is not a
      crucial factor which determined the immobilization of cells.

PMID- 19153001
TI  - Should all patients with non-muscle-invasive bladder cancer receive early
      intravesical chemotherapy after transurethral resection? The results of a
      prospective randomised multicentre study.
AB  - BACKGROUND: To decrease recurrences in non-muscle-invasive bladder cancer
      (NMIBC), the European Association of Urology (EAU) guidelines recommend
      immediate, intravesical chemotherapy after transurethral resection (TUR) for all
      patients with Ta/T1 tumours. OBJECTIVE: To study the benefits of a single, early,
      intravesical instillation of epirubicin after TUR in patients with low- to
      intermediate-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: In this prospective
      randomised multicentre trial, 305 patients with primary as well as recurrent low-
      to intermediate-risk (Ta/T1, G1/G2) tumours were enrolled between 1997 and 2004.
      Patients were randomly allocated to receive 80 mg of epirubicin in 50 ml of
      saline intravesically within 24 h of TUR or no further treatment after TUR.
      MEASUREMENTS: The primary end point was time to first recurrence. RESULTS AND
      LIMITATIONS: A total of 219 patients remained for analysis after exclusions. The
      median follow-up time was 3.9 yr. During the study period, 62% (63 of 102) of the
      patients in the epirubicin group and 77% (90 of 117) in the control group
      experienced recurrence (p=0.016). In a multivariate model, the hazard ratio (HR)
      for recurrence was 0.56 (p=0.002) for early instillation of epirubicin versus no
      treatment. In a subgroup analysis, the treatment had a profound recurrence
      reducing effect on patients with primary, solitary tumours, whereas it provided
      no benefits in patients with recurrent or multiple tumours. Furthermore, patients
      with a modified European Organisation for Research and Treatment of Cancer
      (EORTC) risk score of 0-2 with and without single instillation had recurrence
      rates of 41% and 69%, respectively (p=0.003), whereas the corresponding rates for
      those with a risk score of > or = 3 were 81% and 85%, respectively (p=0.35).
      CONCLUSIONS: A single, early instillation of epirubicin after TUR for NMIBC
      reduces the likelihood of tumour recurrence; however, the benefit seems to be
      minimal in patients at intermediate or high risk of recurrence. Future trials
      will determine the value of early instillation in addition to serial
      instillations in NMIBC.

PMID- 19153003
TI  - Nitrogen dioxide formation in the gliding arc discharge-assisted decomposition of
      volatile organic compounds.
AB  - To apply gliding arc discharge (GAD) plasma processing to volatile organic
      compounds (VOCs) emission control, the formation of NO(2) as an undesired
      byproduct needs to be addressed. Comparative results of effluent temperature and
      product concentrations between experiment and thermodynamic equilibrium
      calculation show that the NO(2) formation in dry air GAD is totally out of
      thermodynamic equilibrium. Meanwhile, obvious NO (A(2)Sigma+)) and N(2)(+)
      (B(2)Sigma(u)(+)) are detected as the major reactive species in the dry air GAD
      plasma region. These results suggest that the thermal (or Zeldovich) NO(x)
      formation mechanism is not significant in GAD system, while the energy level and
      the density of electrons in the plasma region will severely influence the NO(2)
      formation. The presence of 500 ppm VOCs in the feed gases shows a limiting
      influence on the NO(2) formation, which is in the order of aromatic hydrocarbon
      (C(6)H(6) and C(7)H(8))>straight-chain hydrocarbon (C(4)H(10) and
      C(6)H(14))>halogenated hydrocarbon (CCl(4)). The influences of VOCs chemical
      structure, supply voltage, feed gas humidity, and reactor geometry on NO(2)
      formation are investigated, and the results correspond to above mechanism
      analysis. Based on the above, the possible pathways of the inhibition of NO(2)
      formation in GAD-assisted VOCs decomposition process are discussed.

PMID- 19153004
TI  - The performance of iodine on the removal of elemental mercury from the simulated
      coal-fired flue gas.
AB  - In order to facilitate the removal of elemental mercury (Hg(0)) in flue gas,
      iodine was used as the oxidant to convert Hg(0) to the oxidized or particulate
      bound form. The removal of Hg(0) by the homogenous gas phase reaction and the
      heterogeneous particle-involved reactions was investigated under various
      conditions, and a method to test the particle-involved reaction kinetics was
      developed. Iodine was found to be efficient in Hg(0) oxidation, with a 2nd-order
      rate constant of about 7.4(+/-0.2)x10(-17)cm(3)molecules(-1)s(-1) at 393 K.
      Nitric oxide showed significant inhibition in the homogenous gas reaction of
      Hg(0) oxidation. The oxidation of Hg(0) with iodine can be greatly accelerated in
      the presence of fly-ash or powder activated carbon. SO(2) slightly reduced Hg(0)
      removal efficiency in the particle-involved reaction. It was estimated that Hg(0)
      removal efficiency was as high as 70% by adding 0.3 ppmv iodine into the flue gas
      with 20 g/m(3) of fly-ash. In addition, the predicted removal efficiency of Hg(0)
      was as high as 90% if 10mg/m(3) of activated carbon and 0.3 ppmv iodine were
      injected into the flue gas with fly-ash. The results suggest that the combination
      of iodine with fly-ash and/or activated carbon can efficiently enhance the
      removal of Hg(0) in coal-fired flue gas.

PMID- 19153005
TI  - The potential of compost-based biobarriers for Cr(VI) removal from contaminated
      groundwater: column test.
AB  - This paper presents the results of a column reactor test, aiming at evaluating
      the performance of a biological permeable barrier made of low-cost waste
      materials, for Cr(VI) removal from contaminated groundwater. A 1:1 by volume
      mixture of green compost and siliceous gravel was tested as reactive medium in
      the experimental activity. A 10mg/l Cr(VI) contaminated solution was used and the
      residual Cr(VI) concentration along the column height and in the outlet was
      determined in the water samples collected daily. Also pH, redox potential and COD
      were analyzed. At the end of the test, the reactive medium was characterized in
      terms of Cr(VI) and total chromium. The Cr(VI) removal efficiency was higher than
      99% during the entire experimental activity. The influence of the biological
      activity on Cr(VI) removal efficiency was evaluated by varying the organic carbon
      and nitrogen dosages in the contaminated solution fed to the system; a removal
      decrease was observed when the organic carbon was not enough to sustain the
      microbial metabolism. The Cr(VI) removal was strictly linked to the biological
      activity of the native biomass of compost. No Cr(III) was detected in the outlet:
      the Cr(III) produced was entrapped in the solid matrix. Two main processes
      involved were: adsorption on the organic-based matrix and reduction into Cr(III)
      mediated by the anaerobic microbial metabolism of the bacteria residing in green
      compost. Siliceous gravel was used as the structure matrix, since its
      contribution to the removal was almost negligible. Thanks to the proven
      efficiency and to the low-cost, the reactive medium used can represent a valid
      alternative to conventional approaches to chromium remediation.

PMID- 19153006
TI  - Large eddy simulation of fire-induced buoyancy driven plume dispersion in an
      urban street canyon under perpendicular wind flow.
AB  - The dispersion of fire-induced buoyancy driven plume in and above an idealized
      street canyon of 18 m (width) x 18 m (height) x 40 m (length) with a wind flow
      perpendicular to its axis was investigated by Fire Dynamics Simulator (FDS),
      Large Eddy Simulation (LES). Former studies, such as that by Oka [T.R. Oke,
      Street design and urban canopy layer climate, Energy Build. 11 (1988) 103-113],
      Gayev and Savory [Y.A. Gayev, E. Savory, Influence of street obstructions on flow
      processes within street canyons. J. Wind Eng. Ind. Aerodyn. 82 (1999) 89-103],
      Xie et al. [S. Xie, Y. Zhang, L. Qi, X. Tang, Spatial distribution of traffic
      related pollutant concentrations in street canyons. Atmos. Environ. 37 (2003)
      3213-3224], Baker et al. [J. Baker, H. L. Walker, X. M. Cai, A study of the
      dispersion and transport of reactive pollutants in and above street canyons--a
      large eddy simulation, Atmos. Environ. 38 (2004) 6883-6892] and Baik et al. [J.
      J. Baik, Y.-S. Kang, J.-J. Kim, Modeling reactive pollutant dispersion in an
      urban street canyon, Atmos. Environ. 41 (2007) 934-949], focus on the flow
      pattern and pollutant dispersion in the street canyon with no buoyancy effect.
      Results showed that with the increase of the wind flow velocity, the dispersion
      pattern of a buoyant plume fell into four regimes. When the wind flow velocity
      increased up to a certain critical level, the buoyancy driven upward rising plume
      was re-entrained back into the street canyon. This is a dangerous situation as
      the harmful fire smoke will accumulate to pollute the environment and thus
      threaten the safety of the people in the street canyon. This critical re
      entrainment wind velocity, as an important parameter to be concerned, was further
      revealed to increase asymptotically with the heat/buoyancy release rate of the
      fire.

PMID- 19153007
TI  - An attractive agro-industrial by-product in environmental cleanup: dye
      biosorption potential of untreated olive pomace.
AB  - This research deals with the evaluation of highly available and cost effective
      waste biomass of olive pomace for the removal of reactive textile dye, RR198 from
      aqueous medium and a real effluent. The experiments were conducted to assess the
      effects of process variables such as initial pH, biosorbent dosage, contact time,
      temperature and ionic strength. The results showed that the highest dye
      biosorption capacity was found at pH 2 and the needed time to reach the
      biosorption equilibrium was 40 min with a biosorbent concentration of 3.0 g L(
      1). The sorption kinetics of dye was best described by the pseudo-second-order
      kinetic model. The equilibrium biosorption data were analyzed by Langmuir,
      Freundlich and Dubinin-Radushkevich isotherm models and the results from the
      isotherm studies showed that the RR198 biosorption process occurred on a
      homogenous surface of the biosorbent. The waste biomass of olive oil industry
      displayed biosorption capacities ranging from 6.05 x 10(-5) to 1.08 x 10(-4)mol
      g(-1) at different temperatures. The negative values of Delta G degrees and the
      positive value of Delta H degrees suggest that the biosorption process for RR198
      was spontaneous and endothermic. Dye-biosorbent interactions were examined by
      FTIR and SEM analysis. Finally, high biosorption yield of olive waste for the
      removal of RR198 dye from real wastewater makes it possible that the olive pomace
      could be applied widely in wastewater treatment as biosorbent taking into account
      that no pretreatment on the solid residue is carried out.

PMID- 19153008
TI  - Sorption of arsenate and dichromate on polymerin, Fe(OH)x-polymerin complex and
      ferrihydrite.
AB  - Dihydrogenarsenate [H(2)AsO(4)(-), As(V)] or dichromate [Cr(2)O(7)(2-), Cr(VI)]
      at pH=4.0 showed to be sorbed on a Fe(OH)(x)-polymerin complex and ferrihydrite
      to a greater extent than on polymerin, the organic polymeric fraction of olive
      oil mill wastewater (OMW). In particular, the maximum amount (x(m)) of arsenate
      sorbed on Fe(OH)(x)-polymerin complex was similar to that on ferrihydrite (880.26
      and 743.02 mmol kg(-1), respectively), and was much greater than that sorbed on
      polymerin (384.25 mmol kg(-1)). The sorption of dichromate was to a comparable
      extent on Fe(OH)(x)-polymerin complex and ferrihydrite (205.90 and 254.88 mmol
      kg(-1), respectively). Cr(III), a less toxic chromium form, mainly, and Cr(V)
      were indeed the effective forms sorbed on polymerin (200 mmol kg(-1)), as a
      consequence of the redox reaction of the strongly toxic Cr(VI) with the CH(2)OH
      groups of the polysaccharide moiety of this bio-sorbent, according to the data
      deriving from XPS and DRIFT analyses. The potential exploitation of the selected
      sorbents for the removal of As(V) or Cr(VI) from aqueous effluents is briefly
      discussed.

PMID- 19153009
TI  - Treatment of cyanide effluents by oxidation and adsorption in batch and column
      studies.
AB  - In this study the removal of free cyanide from aqueous solutions by air oxidation
      and adsorption was investigated. Effects of air and pure oxygen, and catalyst on
      the rate and extent of the removal of cyanide were studied. It was found that the
      oxidative removal of cyanide by air/oxygen was very limited although it tended to
      improve in the presence of pure oxygen and catalyst such as activated carbon (AC)
      and copper sulphate. In the presence of continuous aeration, the non-oxidative
      removal of cyanide was correlated with a decrease in pH effected apparently by
      the transfer of carbon dioxide from air phase into the medium. The removal of
      cyanide by adsorption on activated carbon, nut shell (NS) and rice husk (RH) was
      also examined. Adsorption capacity of activated carbon was shown to be
      significantly enhanced via impregnation of activated carbons with metals such as
      copper (AC-Cu) and silver (AC-Ag). In the column tests, the breakthrough capacity
      of adsorbents was found to be in an increasing order of RH<AC<AC-Cu<<AC-Ag.

PMID- 19153011
TI  - The influence of Cu addition on precipitation in Fe-Cr-Ni-Al-(Cu) model alloys.
AB  - Precipitation in Fe-Cr-Ni-Al-(Cu) model alloys was investigated after ageing for
      0.25, 3, 10 and 100h at 798K. Characterization of nanoscale precipitates was
      performed using three-dimensional atom probe microscopy and transmission electron
      microscopy. The precipitates are found to be enriched in Ni and Al (Cu) and
      depleted in Fe and Cr. After 0.25h of ageing the number density of precipitates
      is approximately 8x10(24)m((-3)), their volume fraction is about 15.5% and they
      are near-spherical with an average diameter of about 2-3nm. During further ageing
      the precipitates in the both alloys grow, but the coarsening behaviour is
      different for both alloys. The precipitates of the Cu-free alloy grow much faster
      compared with the Cu-containing alloy and their density decreases. Precipitates
      in Cu-free alloy change to plate shaped even after 10h of ageing, whereas those
      of Cu-containing alloy remain spherical up to 10h of ageing. The influence of Cu
      addition on precipitation in these model alloys is discussed with respect to the
      different coarsening mechanisms.

PMID- 19153010
TI  - Assessment of trace metal levels in some moss and lichen samples collected from
      near the motorway in Turkey.
AB  - In this study, 14 different lichen and moss samples were collected from near the
      Sivas-Tokat motorway (5-25 m), control samples were collected from uncontaminated
      locations (1000-3000 m) during 2005. Samples were analyzed using flame and
      graphite furnace atomic absorption spectrometry after microwave digestion. The
      maximum metal concentrations were found to be as 468.1 microg/g (Fe), 270.5
      microg/g (Mn), 67.6 microg/g (Zn), 53.3 microg/g (Pb), 79.6 microg/g (Ni), 33.9
      microg/g (Cr), 29.6 microg/g (Cu) and 5.7 microg/g (Cd) for mosses, 455.5
      microg/g (Fe), 170.5 microg/g (Mn), 77.6 microg/g (Zn), 6.5 microg/g (Pb), 10.1
      microg/g (Ni), 3.8 microg/g (Cr), 25.6 microg/g (Cu) and 1.5 microg/g (Cd)
      microg/g for lichens. The concentration of trace metals in samples is depended on
      moss and lichen species. Some species is accumulated trace metals at high ratio.

PMID- 19153012
TI  - Development of a real-time PCR assay for the detection of Trichinella spiralis in
      situ.
AB  - Trichinellosis is a widespread zoonotic disease caused by nematodes of the genus
      Trichinella. Most human infections are caused by Trichinella spiralis, with pig
      meat being the main source of infection. As a consequence, all countries in the
      EU inspect slaughtered animals to prevent the distribution of infected meat to
      consumers. However, Trichinella spp. infect nearly all orders of mammals and so
      wildlife monitoring is often required in regions that want to provide evidence of
      negligible risk of infection in pigs. Surveys of the parasite in the Red fox are
      generally accepted as evidence of the wildlife reservoir. The EU reference method
      of detection in food animals for human consumption involves digestion of the host
      muscle followed by microscopic screening of the resultant sediment for trichinae
      and the method has been adapted for use with foxes. This work describes the
      development of a real-time PCR assay for the detection of Trichinella in fox
      tissue. The assay was designed to the Internal Transcribed Spacer 2 region of the
      Trichinella genome. Initial assay development was carried out using infected
      mouse tissue, as positive foxes have not been reported in the UK since 1957. The
      developed assay, which was shown to be specific for T. spiralis, was then tested
      using fox muscle spiked with isolated larvae at the rate of 1 larva per gram
      (LPG) of muscle tissue, as this is the theoretical detection limit using the
      digest method, as well as 0.5 and 0.1 LPG. The PCR assay was shown to detect the
      larvae at the higher infection rates and, by testing dilutions of the extracted
      DNA, it was demonstrated that a potential limit of detection of approx. 0.01
      larvae per gram of tissue homogenate may be possible.

PMID- 19153013
TI  - Evaluation of the FAMACHA system for detecting the severity of anaemia in sheep
      from southern Italy.
AB  - Since it was first developed in South Africa, the FAMACHA system has been
      successfully tested in different geographic area where Haemonchus contortus is
      the major gastrointestinal (GI) strongyle species of sheep. The present study,
      the first on the use of the FAMACHA system in Italy, was aimed at obtaining a
      complete haematological profile in sheep with GI strongyle infection, in order to
      evaluate the validity of the FAMACHA system for detecting the severity of anaemia
      in sheep from southern Italy. Between April and September 2006, 793 blood and
      faecal samples were collected from 137 adult sheep of different local breeds of
      the Campania region (southern Italy). Each study animal was monthly subjected to
      blood collection, GI strongyle fecal egg counts (FEC) and a complete clinical
      examination, with particular attention to the colour of ocular mucous membranes.
      The FAMACHA score values (from 1 to 5) were compared to Hematocrit (Hct) and
      Haemoglobin (Hb) values. Considering the FAMACHA score number "3" as borderline
      value for anaemia, the eye score values for anaemic animals were considered in
      the categories of 4 and 5 (Group 4-5) or of 3, 4 and 5 (Group 3-4-5),
      respectively. Anaemia due to GI strongyle infection was considered when the Hct
      and/or Hb values were under 27% and 9g/dl, respectively. The correlation between
      FAMACHA score and both Hb and Hct was significant (P<0.001) and negative;
      however, the low correlation coefficients indicated a weak negative association
      between FAMACHA and either Hb and Hct parameters. The sensitivity, specificity,
      predictive negative value (NPV) and predictive positive value (PPV) of the
      FAMACHA system were calculated. The highest values of sensitivity were 66% and
      60% in the Group 3-4-5 for Hct and Hb, respectively. The highest values of
      specificity were 98% in the Group 4-5, for Hb and Hct, respectively. In the Group
      3-4-5, the specificity was 60% and 62% for Hb and Hct, respectively. The NPV was
      92% (Hct) and 84% (Hb) in the Group 3-4-5, while it was 87% (Hct) and 78% (Hb) in
      the Group 4-5. The PPV, for the others categories considered (Hb, Hct, Group 4-5
      and 3-4-5), was always below 54%. In conclusion, in the present study, the
      FAMACHA system showed a low sensitivity in detecting anemic sheep; these findings
      indicate that in southern Italy, under our experimental conditions, FAMACHA may
      represent an additional element that can integrate clinical examinations. It is
      important that such evaluations are performed in each region before the system is
      implemented, as there could be local issues that affect the accuracy of the
      system.

PMID- 19153014
TI  - Depression as an evolutionary adaptation: implications for the development of
      preclinical models.
AB  - Several authors have suggested that rather than being a disease state, depression
      is an evolutionary adaptation to human social organization. Adaptations are
      produced in response to selection pressures and similar adaptations may easily
      have evolved in a range of other species. The current paper seeks to identify the
      social pressures that may lead to a species developing depression as an
      adaptation and the potential benefits that this may confer. It also examines
      whether rats and mice, the species most commonly used to model depression in the
      laboratory, have social organizations in which selection pressures towards the
      development of depression as an adaptation are likely to exist. It is proposed
      that depression is a useful adaptation in group-living animals, where there is
      competition for a social rank that gives reproductive advantage over others. The
      cluster of symptoms associated with depression include altered activity patterns,
      reduced sociability and appetite, and increased submissiveness. This combination
      strongly suggests that the function of depression is to reduce the likelihood of
      an individual being subject to further attack once they have lost social status
      and so increase their chances of survival in the period immediately following
      this. Successful transition from high to low status may provide further
      opportunities to reproduce. Hence, animals that become depressed during this
      critical period gain a reproductive advantage over those that do not, as these
      are either killed or expelled from the group. Wild mice do not have social
      hierarchies and are highly territorial. Wild rats do have social hierarchies
      however these only compete for reproductive advantage at the level of the sperm,
      and social status does not translate into significantly greater access to mates.
      Therefore, there are no selection pressures in these species towards the
      development of depression and so it is most unlikely that rats and mice have this
      adaptation. It is concluded that current models of depression based on rats and
      mice are in reality models of monoamine activity and that progression beyond this
      tautology requires future models to be developed using species selected on the
      basis of their social organizations in the wild. Hendrie and Pickles, Medical
      Hypotheses.

PMID- 19153015
TI  - Diagnostic utility of CD56 immunohistochemistry in papillary carcinoma of the
      thyroid.
AB  - Diagnosis of papillary thyroid carcinoma (PTC), in many but not all cases, is an
      easily achievable diagnosis with almost minimal interobservable variability
      between pathologists. However, some cases of PTC, particularly the follicular
      variant, are quite challenging and show wide interobservable variability even
      among expert thyroid pathologists. Since proper diagnosis of PTC is crucial as it
      affects patients' clinical management and prognosis, indications of PTC must be
      clearly apparent to be an objective rather than a subjective diagnosis.
      Unfortunately, to date, immunohistochemistry and molecular studies have failed to
      fully solve this problem. In this study, we assessed the protein expression and
      loss using antibodies against CD56 in normal follicular thyroid epithelium,
      follicular thyroid lesions, and follicular thyroid neoplasms in an attempt to
      evaluate its diagnostic value. A total of 185 cases were studied with tissues
      from 75 carcinomas (72 papillary, 2 follicular, 1 Hurthle cell) and 35 adenomas
      (32 follicular and 3 Hurthle cell) evaluated by immunohistochemistry for the
      expression of this marker. Non-neoplastic thyroids included 65 cases: nodular
      hyperplasia (n=25), thyrotoxic hyperplasia (Grave's disease) (n=5), lymphocytic
      thyroiditis (n=19), and Hashimoto's thyroiditis (n=6). Ten cases of normal
      thyroids from radical laryngectomies for laryngeal squamous cell carcinomas were
      also studied. The marker pattern and intensity of staining were scored. Positive
      expression of the markers in 10% or more of follicular epithelium within the
      tumor or lesional cells was considered positive. An expression of <10% was
      considered to be negative. Diffuse CD56 expression was consistently present in
      normal, lesional, and neoplastic follicular epithelium, except for PTC, including
      the follicular variant. We concluded that CD56 is of value to distinguish PTC
      from other thyroid follicular pathology/histology with a sensitivity of 100% and
      a specificity of 100%. We suggest that CD56 is extremely useful in the diagnosis
      of PTC, including the follicular variant, and to distinguish it from other
      follicular cell-derived thyroid tumors/lesions. Application of CD56 by a group of
      expert pathologists on a larger series of follicular thyroid neoplasms of
      uncertain malignant potentials may potentially provide an objective diagnostic
      tool.

PMID- 19153016
TI  - Re-evaluation of 6th edition of AJCC staging system for nasopharyngeal carcinoma
      and proposed improvement based on magnetic resonance imaging.
AB  - PURPOSE: To use magnetic resonance imaging to re-evaluate and improve the 6th
      edition of the International Union Against Cancer/American Joint Committee on
      Cancer staging system for nasopharyngeal carcinoma. METHODS AND MATERIALS: We
      performed a retrospective review of the data from 924 biopsy-proven nonmetastatic
      nasopharyngeal carcinoma cases. All patients had undergone magnetic resonance
      imaging examinations and received radiotherapy as their primary treatment.
      RESULTS: The T classification, N classification, and stage group were independent
      predictors. No significant differences in the local failure hazards between
      adjacent T categories were observed between Stage T2b and T1, Stage T2b and T2a,
      and Stage T2b and T3. Although the disease failure hazards for Stage T1 were
      similar to those for Stage T2a, those for Stage T2b were similar to those for
      Stage T3. Survival curves of the different T/N subsets showed a better
      segregation when Stage T2a was downstaged to T1, T2b and T3 were incorporated
      into T2, and the nodal greatest dimension was rejected. The disease failure
      hazard for T3N0-N1 subsets were similar to those of the T1-T2N1 subsets belonging
      to Stage II; the same result was found for the T4N0-N2 subsets in the sixth
      American Joint Committee on Cancer staging system. However, the staging system we
      propose shows more consistent hazards within the same stage group and better
      survival discrimination among T categories, N categories, and overall stages.
      CONCLUSION: Using the 6th American Joint Committee on Cancer staging system
      produces an acceptable distribution of patient numbers and segregation of
      survival curves among the different stage groups. The prognostic accuracy of the
      staging system could be improved by recategorizing the T, N, and group stage
      criteria.

PMID- 19153017
TI  - Patterns of methamphetamine use and symptoms of depression among young adults in
      northern Thailand.
AB  - INTRODUCTION: Depression often co-occurs with amphetamine type stimulant use and
      can negatively impact drug treatment outcomes. Understanding the temporal
      relationship between depressive symptoms and methamphetamine use can further
      inform both treatment and mental health options. METHODS: Methamphetamine users
      aged 18-25 years were enrolled in a 12-month randomized behavioral trial in
      Thailand. Questionnaires were administered every 3 months and included
      information on substance use and depressive symptoms. Pattern of methamphetamine
      use during follow-up was characterized into four groups: early cessation, late
      cessation, relapse and persistent use. Multinomial logistic regression was used
      to determine the impact of baseline depressive symptoms (CES-D score and % > or
      =22) on patterns of methamphetamine use during follow-up. Linear and logistic
      regression was used to determine the impact of patterns of methamphetamine use on
      depressive symptoms at the end of the trial. RESULTS: No association was found
      between baseline depressive symptoms and subsequent patterns of methamphetamine
      use. A significant relationship was found between patterns of methamphetamine use
      and ensuing depressive symptoms, with those achieving cessation experiencing
      lower levels of depressive symptoms. DISCUSSION: Many symptoms of depression may
      resolve with cessation or reduction in methamphetamine use. Clinical and
      community-based efforts that facilitate drug users' attempts to stop using drugs
      should be supported as they may contribute to positive cessation outcomes and
      help to improve overall mental health.

PMID- 19153018
TI  - Real-time RT-PCR for detection of equine influenza and evaluation using samples
      from horses infected with A/equine/Sydney/2007 (H3N8).
AB  - Equine influenza (EI) virus (H3N8) was identified in the Australian horse
      population for the first time in August 2007. The principal molecular diagnostic
      tool used for detection was a TaqMan real-time reverse transcription-polymerase
      chain reactions (RT-PCR) assay specific for the matrix (MA) gene of influenza
      virus type A (IVA). As this assay is not specific for EI, we developed a new EI
      H3-specific TaqMan assay targeting the haemagglutinin (HA) gene of all recent EI
      H3 strains. The IVA and the EI H3 TaqMan assays were assessed using in vitro
      transcribed RNA template, virus culture, diagnostic samples from the outbreak and
      samples from experimentally infected horses. The EI H3 TaqMan assay had a higher
      diagnostic sensitivity (DSe) when compared to the IVA TaqMan assay and also when
      using a conventional PCR for EI H3 as a standard of comparison. The performance
      of both TaqMan assays was compared with an antigen detection ELISA and virus
      isolation using nasal swabs collected daily from horses experimentally infected
      with the outbreak strain A/equine/Sydney/2888-8/2007. The EI H3 TaqMan assay was
      the most sensitive of the assays, able to detect EI from day 1 or 2 post
      challenge, as early as virus isolation, and before clinical signs of disease were
      observed.

PMID- 19153019
TI  - Age- and sex-related changes in the soft tissues of the orbital region.
AB  - The orbital region plays a predominant role in the evaluation of the craniofacial
      complex. In the current study information about normal sex-related dimensions of
      the orbital region, and growth, development and aging, were provided. The three
      dimensional coordinates of several soft-tissue landmarks on the orbits and face
      were obtained by a non-invasive, computerized electromagnetic digitizer in 531
      male and 357 female healthy subjects aged 4-73 years. From the landmarks,
      biocular and intercanthal widths, paired height and inclination of the orbit
      relative to both the true horizontal (head in natural head position) and
      Frankfurt plane, length and inclination of the eye fissure, the relevant ratios,
      soft-tissue orbital area, were calculated, and averaged for age and sex.
      Comparisons were performed by factorial analysis of variance. Biocular and
      intercanthal widths, length of the eye fissure, soft-tissue orbital area, and the
      inclination of the orbit relative to the true horizontal, were significantly
      larger in men than in women (p<0.01), with a significant effect of age (p<0.001),
      and significant agexsex interactions (p<0.001). Orbital height, and the height-to
      width ratio increased as a function of age (p<0.001), but without gender-related
      differences. The inclination of the orbit relative to Frankfurt plane, and the
      inclination of the eye fissure did not differ between men and women, but modified
      as a function of age (p<0.001), with different sex-related patterns (sexxage
      interaction, p<0.001). On average, the paired measurements were symmetric, with
      similar values within each sex and age group. Overall, when compared to
      literature data, some differences were found due to both ethnicity, and different
      instruments. Nevertheless, during childhood, adolescence, and young adulthood,
      the age-related trends for linear dimensions were similar to those found in
      previous studies, while no previous data exist for older adults. During aging an
      increment in soft-tissue orbital area was found, with a progressive downward
      shift of landmark orbitale. Data collected in the present investigation could
      serve as a data base for the quantitative description of human orbital morphology
      during normal growth, development and aging. Forensic applications (evaluations
      of traumas, craniofacial alterations, teratogenic-induced conditions, facial
      reconstruction, aging of living and dead persons, personal identification) may
      also benefit from age- and sex-based data banks.

PMID- 19153020
TI  - Air pressure-sensing ability of the middle ear-Investigation of sensing regions
      and appropriate measurement conditions.
AB  - OBJECTIVE: To study the association between ear diseases and the ability of the
      middle ear to sense air pressure changes, we elucidated the appropriate
      conditions for measurements and confirmed the pressure-sensing regions while
      quantitatively assessing the pressure-sensing ability of normal ears and of ears
      with traumatic perforation of the tympanic membrane. METHODS: In 318 normal ears
      (159 volunteers), an air pressure of 40daPas(-1) was loaded on to the external
      auditory canals to measure the minimum pressure sensed by subjects as a result of
      air pressure changes. The minimum pressure was defined as the minimum sensory
      threshold for air pressure loading (MSTAP; daPa). In 40 of 318 normal ears (20
      volunteers), the MSTAP was measured at 10daPas(-1). Next, topical anesthesia was
      administered to 5 normal ears (5 volunteers), and the MSTAP was measured. In 7
      ears with traumatic tympanic membrane perforation (7 cases), the MSTAP was also
      measured at the first medical examination. The data were analyzed using Stat View
      5.0 (SAS Institute Inc., Cary, NC, USA). To test the significance of the data,
      the Mann-Whitney U-test and the Wilcoxon test were used. RESULTS: The mean (+/
      S.D.) MSTAP at 40daPas(-1) was -39.2+/-12.2daPa with negative pressure and 39.5+/
      12.4daPa with positive pressure. At 10daPas(-1), the MSTAP was -70.3+/-25.0daPa
      with negative pressure and 72.5+/-22.7daPa with positive pressure, and both the
      mean and S.D. values were higher than those obtained at 40daPas(-1). Briefly, the
      MSTAP at 40daPas(-1) produced less variance than that at 10daPas(-1). The MSTAP
      demonstrated gender- and age-related variations. Moreover, it increased after
      topical anesthesia was administered to the tympanic membrane. The MSTAP in
      patients with traumatic tympanic membrane perforation was -205.0+/-26.3daPa with
      negative pressure and 206.0+/-26.7daPa with positive pressure, and was
      significantly higher than that observed in case of normal ears. CONCLUSION: For
      obtaining accurate measurements while estimating the pressure-sensing ability of
      the middle ear, the rate of pressure loading should be considered. Although we
      assume that the middle ear has pressure-sensing regions other than the tympanic
      membrane, we conclude that the tympanic membrane is the most sensitive pressure
      sensing region in the middle ear.

PMID- 19153021
TI  - Developmental characteristics of visual cognitive function during childhood
      according to exploratory eye movements.
AB  - To evaluate the development of visual cognitive function in childhood, we
      examined exploratory eye movements in 84 healthy subjects viewing picture-based
      stimuli. Age-defined groups included 4- to 6-year-olds, 7-year-olds, 10-year
      olds, 14-year-olds, 16-year-olds, and adults. In each group, 7 subjects were male
      and 7 were female. Exploratory eye movements, recorded as gaze points using an
      eye-mark recorder, were analyzed in terms of the total number of gaze points
      (TNGP); total eye-scanning length of gaze points (TESL); total number of gaze
      points on the left (l TNGP) and right (r TNGP) of the screen; and responsive
      search score (RSS) on the left (l RSS) and right (r RSS) of the screen. Both the
      TESL and TNGP increased significantly with age. The TESL and TNGP of 16-year-olds
      and adults viewing a repeat-comparison figure were significantly greater than
      when viewing a comparison figure. During the repeat-comparisons, the TNGP in 4-
      to 6-year-olds was greater on the right than the left; the opposite was true in
      16-year-olds and adults. The RSS in 4- to 10-year-olds was greater on the right
      than the left; 16-year-olds and adults showed the reverse findings. Thus, in the
      repeat-comparison task, TNGP, TESL, TNGP, and RSS differences between left and
      right visual fields are useful biologic markers for estimating the development of
      visual cognitive function.

PMID- 19153022
TI  - MR imaging for predicting the recurrence of pancreatic carcinoma after surgical
      resection.
AB  - OBJECTIVE: To study the relationship of characteristics of pancreatic carcinoma
      on MR imaging to tumor recurrence time after surgical resection. MATERIALS AND
      METHODS: Twenty-seven patients with pancreatic carcinoma were followed up at
      least 2 years after surgical resection of the tumor. All patients had MR imaging
      within 1 month before surgery. The tumor's size, signal intensity, local and
      vascular invasion, abdominal lymphadenopathy on MR imaging and the positive
      surgical margin were noted. The results from MR imaging were compared with the
      duration after surgery until tumor recurrence and with the positive surgical
      margin. RESULTS: 59% of patients had various degree of extrapancreatic invasion.
      The tumor recurrence times were, respectively, 24+/-21 months and 26+/-29 months
      in patients with and without vascular invasion (P=0.79). The combination of
      vascular with local invasion showed a correlation to the time of tumor recurrence
      (r=-0.34; P<0.05). Patients with positive surgical margins had a higher local
      invasion score on MR imaging and a shorter recurrence time than those with
      negative surgical margins. The number and size of lymph nodes were not related
      with tumor recurrence time. CONCLUSION: MR imaging was useful for predicting the
      recurrence of pancreatic carcinoma after surgical resection. Local invasion
      associated with and without vascular invasion on MR imaging was the indicator for
      the tumor recurrence.

PMID- 19153023
TI  - The medical consultation viewed as a value chain: a neurobehavioral approach to
      emotion regulation in doctor-patient interaction.
AB  - OBJECTIVE: To present a model of the medical consultation as a value chain, and
      to apply a neurobehavioral perspective to analyze each element in the chain with
      relevance for emotion regulation. METHODS: Current knowledge on four elements in
      medical consultations and neuroscientific evidence on corresponding basic
      processes are selectively reviewed. RESULTS: The four elements of communication
      behaviours presented as steps in a value chain model are: (1) establishing
      rapport, (2) patient disclosure of emotional cues and concerns, (3) the doctor's
      expression of empathy, and (4) positive reappraisal of concerns. CONCLUSION: The
      metaphor of the value chain, with emphasis on goal orientation, helps to
      understand the impact of each communicative element on the outcome of the
      consultation. Added value at each step is proposed in terms of effects on outcome
      indicators; in this case patients affect regulation. Neurobehavioral mechanisms
      are suggested to explain the association between communication behaviour and
      affect regulation outcome. PRACTICE IMPLICATIONS: The value chain metaphor and
      the emphasis on behaviour-outcome-mechanisms associations may be of interest as
      conceptualizations for communications skills training.

PMID- 19153024
TI  - Circulating tumour cells during laparoscopic and open surgery for primary colonic
      cancer in portal and peripheral blood.
AB  - BACKGROUND: The objective of this study was to detect and quantify circulating
      tumour cells (CTC) in peripheral and portal blood of patients who had open or
      laparoscopic surgery for primary colonic cancer. METHODS: Patients in the
      laparoscopic-group were operated on in a medial to lateral approach ("vessels
      first"), in the open-group a lateral to medial approach was applied. The
      enumeration of CTC was performed with the CellSearch System. Intra-operative
      samples were taken paired-wise (from peripheral and portal circulation) directly
      after entering the abdominal cavity (T1), after mobilisation of the tumour baring
      segment (T2), and after tumour resection (T3). Ploidy of both the CTC and tissue
      of the primary tumour was determined for chromosome 1, 7, 8 and 17. RESULTS:
      Thirty-one patients were included; 18 patients had open surgery, 13 patients were
      operated on laparoscopically. The percentage of samples with CTC at T1 was 7% in
      peripheral blood and 54% in portal blood (p=0.002). At T2, 4% and 31%
      respectively (p=0.031). And at T3, 4% and 26% respectively (p=0.125). The
      cumulative percentage of samples with CTC was significantly higher during open
      surgery as compared to the laparoscopic approach. Both the CTC and tissue of the
      primary tumour were diploid for chromosome 1, 7, 8 and 17. CONCLUSION: The
      detection rate and quantity of CTC is significantly increased intra-operatively
      and is significantly higher in portal blood compared to peripheral blood.
      Significantly less CTC were detected during laparoscopic surgery probably as
      result of the medial to lateral approach.

PMID- 19153025
TI  - Pulmonary metastasectomy in colorectal cancer: time for a trial.
AB  - Pulmonary metastasectomy is undertaken for a range of cancers. The questions we
      raise here are specifically related to colorectal cancer, the commonest tumour
      for which pulmonary metastasectomy is undertaken. The primary objective of
      metastasectomy is to increase survival. There are no randomised trials in support
      of this practice nor are there any other forms of controlled studies. We present
      a critical look at the assumption of efficacy for this surgery and propose that a
      trial is needed and suggest a trial design.

PMID- 19153026
TI  - [Suspected child abuse: a perilous situation for practician?].

PMID- 19153027
TI  - A case of coronary artery fistula between a coronary artery and the left atrium
      following maze procedure.
AB  - The authors report a case of a coronary artery fistula (CAF) after mitral
      valvuloplasty and a maze procedure. A 73-year-old man was admitted to the
      hospital with congestive heart failure. He had undergone mitral valvuloplasty and
      a maze procedure 10 years previously. An abnormal Doppler flow signal in the left
      atrium was incidentally found on transthoracic echocardiography. It was diagnosed
      as a CAF on transesophageal echocardiography and other imaging modalities. The
      detection of the abnormal flow just after the operation suggested a causal
      relationship between this fistula and the preceding surgical procedure. Acquired
      CAF following cardiac surgery is a rare abnormality. However, if abnormal flow is
      found on transthoracic echocardiography after cardiac surgery, this abnormality
      should be kept in mind.

PMID- 19153028
TI  - Changes in soft tissue profile after mandibular setback surgery in Class III
      subjects.
AB  - The aim of this study was to investigate changes in hard and soft tissue profile
      after mandibular setback surgery. Lateral cephalograms of 25 Class III subjects
      were assessed before and 1.5+/-0.4 years after mandibular setback surgery. Paired
      t test, Pearson correlation test and linear regression analysis were used to
      evaluate the changes in soft tissue profile. Significant changes were found in
      skeletal (SNB -3.6+/-0.9 degrees, ANB 3.7+/-1.0 degrees, overjet 5.0+/-1.2 and
      overbite 2.5+/-1.1 mm, P<0.001), soft tissue (facial convexity 5.9+/-1.6 degrees,
      P<0.001; labiomental fold 0.6+/-0.6 mm, P<0.001; upper and lower lip protrusion
      0.5+/-0.8 mm, P<0.01; -3.3+/-1.2 mm, P<0.001), and upper and lower lip lengths
      (0.9+/-1.2mm, P<0.01; -1.8+/-2.1 mm, P<0.001). Correlations were found between
      facial convexity and SNB and ANB angles and between upper lip length and SNB and
      ANB angles. The change in lower lip length was correlated with SNB, ANB, overjet
      and overbite. Lower lip retrusion was correlated with overjet and a significant
      correlation was found between the retrusion of lower incisor and lower lip.
      Mandibular setback surgery was effective in producing an orthognathic profile in
      adult Class III subjects with mandibular prognathism.

PMID- 19153029
TI  - Effects of the preoperative administration of Yunnan Baiyao capsules on
      intraoperative blood loss in bimaxillary orthognathic surgery: a prospective,
      randomized, double-blind, placebo-controlled study.
AB  - Yunnan Baiyao is a well-known Chinese herbal medicine that has been used as a
      haemostatic drug for nearly 100 years. The aim of this clinical trial was to
      evaluate the efficacy and safety of Yunan Baiyao capsules on the reduction of
      blood loss in bimaxillary orthognathic surgery. 87 consecutive patients scheduled
      for simultaneous maxillary Le Fort I osteotomies and bilateral sagittal split
      ramus osteotomies (BSSRO) were enrolled in a prospective, randomized, double
      blind, placebo-controlled clinical trial. Patients were administered Yunnan
      Baiyao capsules or placebo capsules, orally for 3 days before surgery.
      Intraoperative blood loss was estimated and the safety of Yunnan Baiyao capsules
      was evaluated. The total blood loss in the Yunnan Baiyao group (mean, 330.5+/
      134.4 ml) was significantly lower than in the control group (mean, 420.3+/-175.9
      ml). No allergic reactions, thromboembolic events or other side effects were
      recorded in this trial. It can be concluded that the preoperative use of Yunnan
      Baiyao capsules, in combination with hypotension anaesthesia, results in a
      reduction in intraoperative blood loss in bimaxillary orthognathic surgery.
      Yunnan Baiyao capsules are an effective and safe haemostatic Chinese medicine.

PMID- 19153031
TI  - In vitro activities of daptomycin, tigecycline, linezolid and eight other
      antibiotics, alone and in combination, against 41 Staphylococcus spp. clinical
      isolates from bone and joint infections.

PMID- 19153030
TI  - Clinico-epidemiological analysis of orofacial rhabdomyosarcoma in a Nigerian
      population.
AB  - Rhabdomyosarcoma (RMS) is a malignant soft tissue neoplasm, with varying degrees
      of striated muscle cell differentiation and a relative predilection for the head
      and neck region. The objectives of this study were to determine the clinical and
      histological patterns of RMS, to assess the sociodemographic profile of reported
      RMS cases, and to highlight the management challenges and outcomes of these cases
      in a country lacking resources such as Nigeria. Patients diagnosed with RMS,
      based on clinical and histological evaluation, and recorded in the cancer
      registry of two maxillofacial centres in Nigeria were reviewed. 21 patients met
      the inclusion criteria for this study. Their ages ranged from 24 days to 42
      years. In all of them multiple anatomical sites were involved. The primary site
      of the lesion could not be determined. Embryonal and alveolar subtypes were
      mainly found in the maxilla. There was no statistically significant association
      between the site of the lesion and the histological type (p=0.39). The patients'
      age was statistically significantly associated with the histological type
      (p=0.008). Most patients reported at an advanced stage, contributing to the poor
      prognosis and management outcome of cases evaluated.

PMID- 19153032
TI  - In vitro activity of tigecycline and 10 other antimicrobials against clinical
      isolates of the genus Corynebacterium.
AB  - We studied the in vitro activity of tigecycline and 10 other commonly used
      antibiotics against 135 clinical isolates of non-diphtheria Corynebacterium spp.
      using the Etest system. Tigecycline minimum inhibitory concentrations for 50% and
      90% of the organisms (MIC(50) and MIC(90) values, respectively, in mg/L) were:
      Corynebacterium urealyticum, 0.094 and 0.125; Corynebacterium amycolatum, 0.125
      and 2; Corynebacterium jeikeium, 0.094 and 0.75; Corynebacterium coyleae, 0.064
      and 0.064; Corynebacterium striatum, 0.064 and 1; Corynebacterium aurimucosum,
      0.094 and 0.125; and Corynebacterium afermentans, 0.064 and 0.094. The activities
      of all other antimicrobials were variable, with good activity of glycopeptides,
      linezolid, quinupristin/dalfopristin and daptomycin and with resistance to
      macrolides in a high number of isolates. Tigecycline is a good alternative for
      the therapy of infections caused by non-diphtheria corynebacteria.

PMID- 19153033
TI  - Triazole-resistant candidaemia following posaconazole exposure.

PMID- 19153034
TI  - Effectiveness of low-dose daptomycin in the treatment of vancomycin-resistant
      enterococcal urinary tract infections.

PMID- 19153035
TI  - The effect of sodium cholate aggregates on thermoreversible gelation of PNIPAM.
AB  - Additives like salts and surfactants can alter the phase transition temperature
      of poly(N-isopropylacrylamide) (PNIPAM). The inclusion of a biological surfactant
      like sodium cholate (NaC) into PNIPAM could lead a better biocompatibility when
      the materials are used for biomedical applications. The phase transition behavior
      of PNIPAM was studied in presence of NaC. DSC study shows that the presence of
      NaC broadens the phase transition endotherm of PNIPAM, which is also accompanied
      by a small shift of the critical solution temperature (CST) to lower temperature.
      The results were compared with the optical measurements like, turbidity, DLS,
      fluorescence and rheology and it was observed that optical techniques are the
      best suitable for finding the onset temperature of gelation. The effect of the
      NaC bile salt is in contrast to the effect of conventional surfactants which are
      known to shift the CST to higher values, due to mutual solubilization. A study of
      fluorescence spectroscopic parameters like fluorescence anisotropy, spectral
      shift, intensity and DLS measurements suggest that a NaC-induced aggregation
      could be responsible for this unusual observation.

PMID- 19153036
TI  - Waste-to-energy: A review of the status and benefits in USA.
AB  - The USA has significant experience in the field of municipal solid waste
      management. The hierarchy of methodologies for dealing with municipal solid
      wastes consists of recycling and composting, combustion with energy recovery
      (commonly called waste-to-energy) and landfilling. This paper focuses on waste-to
      energy and especially its current status and benefits, with regard to GHG, dioxin
      and mercury emissions, energy production and land saving, on the basis of
      experience of operating facilities in USA.

PMID- 19153037
TI  - Biofuel cell and phenolic biosensor based on acid-resistant laccase
      glutaraldehyde functionalized chitosan-multiwalled carbon nanotubes nanocomposite
      film.
AB  - To immobilize laccase (Lac) from Trametes versicolor that shows its maximum
      enzymatic activity in acidic aqueous solutions, the biopolymer chitosan (CS) was
      chemically modified with glutaraldehyde (GA) to form GA functionalized CS
      (GAfCS), which was then allowed to react with Lac to form a Lac-GAfCS composite
      that is robust in weakly acidic solutions (two-step protocol), as confirmed by
      quartz crystal microbalance and durability tests. The Lac-GAfCS-multiwalled
      carbon nanotubes (MWCNTs)/glassy carbon (GC) electrode exhibited good catalytic
      activity towards O(2) reduction in the presence of 2,2'-azinobis (3
      ethylbenzothiazoline-6-sulfonate) diammonium salt (ABTS), and the pH-dependent
      enzymatic activity of the immobilized Lac towards O(2) reduction was examined. A
      glucose/air biofuel cell was fabricated, with the Lac-GAfCS-MWCNTs/GC electrode
      as the biocathode and a glucose oxidase (GOx)-GAfCS-MWCNTs/GC electrode as the
      bioanode in a Nafion membrane-separated acetate buffer solution (pH 5.0). The
      biofuel cell output a maximum power density of 9.6 microW/cm(2), an open-circuit
      cell voltage of 0.19V, and a short-circuit current density of 114 microA/cm(2),
      respectively, as measured with an electrochemical noise (ECN) apparatus.
      Furthermore, the Lac-GAfCS-MWCNTs/GC electrode was applied to determine catechol
      in Britton-Robinson buffer solution (pH 3.0), with a linear range of 0.1-50
      microM and a limit of detection of 20 nM. In comparison with the direct use of GA
      for one-pot Lac-GA-CS or Lac-GA crosslinking to immobilize Lac, the use of
      macromolecular GAfCS in the proposed two-step protocol was proven to be less
      harmful to the enzymatic activity and thus more suitable for immobilizing the
      enzyme to construct the biofuel cell and biosensor. This work may be helpful for
      exploiting the popular biocompatible CS as an acid-resistant film matrix for many
      other biotechnology applications, and the proposed two-step crosslinking protocol
      is recommended for high-activity immobilization of other biomolecules.

PMID- 19153038
TI  - Portable optical immunosensor for highly sensitive detection of microcystin-LR in
      water samples.
AB  - Fast and sensitive detection of microcystin-LR (MC-LR) was conducted with a
      portable trace organic pollutant analyzer (TOPA) based on the principle of
      immunoassay and total internal reflection fluorescence. The reusable fiber optic
      probe surface was produced by covalently immobilizing a MC-LR-ovalbumin (MC-LR
      OVA) conjugate onto a self-assembled thiol-silane monolayer of fiber optic probe
      through a heterobifunctional reagent. It has been established that the MC-LR-OVA
      immobilized fiber optic probe is highly resistive to non-specific binding of
      proteins, while bound anti-MC-LR antibody can easily be eluted from the
      immunosurface with high recoveries (more than 150 assay cycles) in the way of
      pepsin solution, without any damage to the surface-immobilized MC-LR derivatives.
      One assay cycle including surface regeneration was less than 20 min. For the
      standard curve, the limit of detection (LOD) of 0.03 microg/L and the
      quantitative detection range of 0.1-10.1 microg/L was obtained when the
      concentration of antibody labeled by Cy5.5 was 0.28 microg/mL. Cross-reactivity
      against a few compounds structurally similar to MC-LR was little. The developed
      immunosensor method was applied to the monitoring of MC-LR in various types of
      water. The recovery of MC-LR added to water samples at different concentrations
      ranged from 80 to 110% with relative standard deviation (R.S.D.) values less than
      5%. The immunoassay performance of the TOPA was validated with respect to
      conventional high-performance liquid chromatography, and the correlation between
      methods was in good agreement (r(2)=0.9978). The TOPA is a portable, easy-to-use,
      and robust immunoassay system and commercially obtained from the company JQ
      environ Co. Ltd. (China).

PMID- 19153039
TI  - Nitric oxide delivery to cancer: why and how?
AB  - Hypoxia and blood flow heterogeneities are characteristics of solid tumours and
      are major obstacles for therapy. Exploiting the biology of nitric oxide (NO), a
      small radical with multiple functions, is particularly attractive to circumvent
      these sources of resistance and to sensitise tumour to cytotoxic treatments such
      as radiotherapy and chemotherapy. Indeed, while NO mediates angiogenic effects,
      NO may also promote tumour perfusion, drug delivery and oxygenation. Different
      strategies to deliver NO to tumours and pertaining to the FECS-EJC award
      laureate's work are reviewed, with a focus on their therapeutic potential. The
      development of techniques to monitor how and to which extent NO delivery
      influences the phenotype of a given tumour in a given patient is also discussed.

PMID- 19153040
TI  - Adzuki bean: a new resource of biocatalyst for asymmetric reduction of aromatic
      ketones with high stereoselectivity and substrate tolerance.
AB  - A new resource of biocatalyst for asymmetric reduction of aromatic ketones has
      been discovered for the first time from a common plant seed, adzuki bean, i.e.
      Phaseolus angularis (Willd.) W.F. Wight. The study investigated the best methods
      to prepare the biocatalyst and its ability to reduce ketones. Our results
      indicated that the biocatalyst from adzuki bean could reduce various aromatic
      ketones at relatively high concentrations (e.g. 100mM), exhibiting excellent
      stereoselectivity (>98% e.e.). In addition, it was found that NADPH acts as the
      reducing cofactor, which can be regenerated by the crude enzyme system itself
      using glucose as an auxiliary substrate.

PMID- 19153041
TI  - Characterization of bioflocculants from biologically aerated filter backwashed
      sludge and its application in dying wastewater treatment.
AB  - In this study, the feasibility of bioflocculant extraction from backwashing
      sludge to reduce its production costs was investigated. Results showed that
      ultrasound and base treatment could significantly enhance bioflocculant
      extraction efficiency, however, flocculating activity was affected. It was
      observed that bioflocculants extracted from sludge of pH 11.0 had no flocculating
      activity. In contrast, bioflocculants extracted from sludge of pH 5.0, named as M
      1, had good flocculating activity. To further study the flocculating activity of
      M-1, factors such as bioflocculant dosage, temperature and pH of the reaction
      solution were tested. The optimal conditions were 6.0mg/l bioflocculant dosage
      and pH 5.0, at a temperature of 10 degrees C. Under these conditions, the
      flocculating rate of kaolin clay was 92.67%. The effectiveness of such
      bioflocculants in the decolorization of synthetically dyed wastewater was then
      examined. In flocculating methylene blue and fast blue in aqueous solutions,
      decolorization efficiency levels were 82.9% and 77.8%, respectively.

PMID- 19153042
TI  - Biosynthetic studies of spiroleptosphol.
AB  - Studies of the biosynthesis of spiroleptosphol (1) revealed that 1 comprised a
      heptaketide (C1, C5-C10, and C12-C18 moiety), two methyl carbons (C19 and C20)
      from methionine, and a C(3) unit (C3, C4, and C11 moiety) derived through the TCA
      cycle.

PMID- 19153043
TI  - Sensitivity and specificity of fall detection in people aged 40 years and over.
AB  - About one third of home-dwelling people over 65 years of age fall each year.
      Falling, and the fear of falling, is one of the major health risks that affects
      the quality of life among older people, threatening their independent living. In
      our pilot study, we found that fall detection with a waist-worn triaxial
      accelerometer is reliable with quite simple detection algorithms. The aim of this
      study was to validate the data collection of a new fall detector prototype and to
      define the sensitivity and specificity of different fall detection algorithms
      with simulated falls from 20 middle-aged (40-65 years old) test subjects.
      Activities of daily living (ADL) performed by the middle-aged subjects, and also
      by 21 older people (aged 58-98 years) from a residential care unit, were used as
      a reference. The results showed that the hardware platform and algorithms used
      can discriminate various types of falls from ADL with a sensitivity of 97.5% and
      a specificity of 100%. This suggests that the present concept provides an
      effective method for automatic fall detection.

PMID- 19153044
TI  - Outcomes for combined anterior and posterior surgical approaches for patients
      with multisegmental cervical spondylotic myelopathy.
AB  - Corpectomy is widely used to treat cervical spondylotic myelopathy (CSM).
      However, when this technique alone is performed at 1 or 2 levels for a
      multisegmental involvement (3 or more vertebrae), the incidence of post-operative
      complications is high. The optimal treatment for multisegmental CSM is still
      debatable. The aim of this study was to assess clinical and radiological outcomes
      for patients with multisegmental CSM who underwent combined anterior and
      posterior (AP) surgical approaches. Forty adults (17 women and 23 men; age range,
      41-76 y) treated at our center between 2004 and 2007 were reviewed
      retrospectively. Their neurological function was assessed at different times
      using the Nurick classification (Grades 0 [root symptoms only] to 5 [wheelchair-
      or bed-bound]). Patients' satisfaction with the surgery was evaluated using
      Odom's criteria (poor, fair, good, or excellent). Pre-operatively, 20% of
      patients were assessed as Nurick Grade 0, 60% as Grade 1, and 20% as Grade 2. At
      the 1-year follow-up, only 10% of patients were assessed as Grade 1. At 1 year
      after surgery, 85% of patients rated their satisfaction with the operation as
      "excellent" and 15% rated it as "good". These outcomes suggest that, when surgery
      is indicated and patients with multisegmental CSM are carefully selected, the
      combined AP approach yields symptom relief comparable to that of corpectomy alone
      and a lower incidence of post-operative complications.

PMID- 19153045
TI  - Aquaporin-4 expression is increased in edematous meningiomas.
AB  - Peritumoral edema is frequently present in meningiomas and can result in serious
      morbidity and mortality. The aquaporins (AQPs) are a family of membrane protein
      water channels with an integral role in water transport and maintenance of fluid
      balance. AQP4, increased in edematous human brain tumors such as astrocytomas and
      metastases, is present in the astrocytic foot processes adjacent to endothelial
      cells and may therefore have a role in cerebral edema formation. The objective of
      this study is to investigate the expression of AQP4 in meningiomas and to
      correlate their expression with peritumoral edema. Fresh human meningioma
      specimens (17) were obtained and immunohistochemical staining and Western blot
      analysis was performed for AQP4. The peritumoral edema index (EI) was calculated
      based on MRI post-processed to calculate the tumor and edema volume.
      Overexpression of AQP4 was associated with significant peritumoral edema.
      Immunohistochemistry showed upregulation of AQP4 throughout the specimens.
      Therefore, we conclude that increased expression of AQP4 is associated with
      peritumoral edema in meningiomas. This suggests that AQP4 overexpression can lead
      to abnormal water transport and edema formation in meningiomas. The inhibition of
      AQP4 water channels is a potential therapeutic option to reduce the adverse
      effects of peritumoral edema in meningiomas.

PMID- 19153046
TI  - Serum vitamin B12, folate, and homocysteine levels and their association with
      clinical and electrophysiological parameters in multiple sclerosis.
AB  - Patients with multiple sclerosis (MS) may have low serum vitamin B12 and folate
      levels and high levels of homocysteine. We aimed to evaluate serum vitamin B12,
      folate, homocysteine, mean corpuscular volume (MCV), hemoglobin (Hb), and
      hematocrit (Hct) levels in patients with MS. We examined the relationship between
      these parameters and age, sex, disease type, age at onset, disease duration,
      Expanded Disability Status Score, immunoglobulin G (IgG) index, oligoclonal band
      presence, visual evoked potentials (VEP) and posterior tibial somatosensory
      evoked potentials (SEP). These parameters were evaluated in 35 patients during an
      acute attack and compared to data collected from 30 healthy individuals (control
      subjects). Serum vitamin B12, folate, homocysteine, Hb, and Hct levels and MCV
      were low in a proportion of patients with MS (20%, 14.3%, 20%, 6.7%, 3.3% and 10%
      respectively), whereas only vitamin B12 and folate levels were low in only 3.3%
      of the control subjects. Homocysteine levels were high in 20% of patients with MS
      but were within normal limits in the control group. Elevated Hct levels were
      significantly correlated (p<0.05) with prolonged posterior tibial SEP P1 and P2
      latencies compared to the control subjects. Patients with MS who had prolonged
      VEP and posterior tibial SEP P1 and P2 latencies also had lower vitamin B12
      levels compared to patients with normal latencies. Thus, we found a significant
      relationship between MS and vitamin B12 deficiency, and also demonstrated a
      relationship between vitamin B12 deficiency, VEP and posterior tibial SEP in MS.

PMID- 19153047
TI  - 5'-O-Aliphatic and amino acid ester prodrugs of (-)-beta-D-(2R,4R)-dioxolane
      thymine (DOT): synthesis, anti-HIV activity, cytotoxicity and stability studies.
AB  - A series of (-)-beta-D-(2R,4R)-dioxolane-thymine-5'-O-aliphatic acid esters as
      well as amino acid esters were synthesized as prodrugs of (-)-beta-D-(2R,4R)
      dioxolane-thymine (DOT). The compounds were evaluated for anti-HIV activity
      against HIV-1(LAI) in human peripheral blood mononuclear (PBM) cells as well as
      for their cytotoxicity in PBM, CEM and Vero cells. Improved anti-HIV potency in
      vitro was observed for the compound 2-4 (5'-O-aliphatic acid esters) without
      increase in cytotoxicity in comparison to the parent drug. Chemical and enzymatic
      hydrolysis of the prodrugs was also studied, in which the prodrugs exhibited good
      chemical stability with the half-lives from 3 h to 54 h at pH 2.0 and 7.4
      phosphate buffer. However, the prodrugs were relatively labile to porcine
      esterase with the half-lives from 12.3 to 48.0 min.

PMID- 19153048
TI  - Neutron radiography determination of water diffusivity in fired clay brick.
AB  - The real time neutron and gamma radiography station at Maria reactor, Institute
      of Atomic Energy, Swierk, Poland, was used to investigate the isothermal water
      absorption into fired clay brick samples. The investigated brick is different
      from the bricks reported in El Abd and Milczarek [2004. Neutron radiology study
      of water absorption in porous building materials: anomalous diffusing analysis.
      J. Phys. D: Appl. Phys. 37, 2305-2313] in density and chemical composition.
      Neutron radiography images were acquired regularly as the absorption time
      elapses. The water content, theta, along the flow direction, x, namely the water
      profiles theta(x,t) and the water front position as a function of the absorption
      time, t, were extracted from neutron radiography images. The results were
      discussed in terms of the macroscopic theory of water infiltration in unsaturated
      porous media. It was shown that the water front position followed the square root
      t-scaling (x(m)=phi(m) square root t) and the profiles (theta-phi) converged to a
      universal one master curve. The water diffusivity was analytically determined
      from the experimental results. It has the so-called hypo-diffusive character,
      namely its gradient with respect to the water content is positive. Neutron
      radiography is a powerful method to distinguish among the unsaturated flow in
      different porous construction materials.

PMID- 19153049
TI  - The Arabidopsis Ethylene-Insensitive 2 gene is required for lead resistance.
AB  - The Arabidopsis Ethylene-Insensitive 2 (EIN2) gene has been shown to be involved
      in the regulation of abiotic and biotic stresses, including ozone stress, high
      salt, oxidative stress and disease resistance. However, little is known about the
      role of EIN2 gene in lead (Pb) resistance in Arabidopsis. In this study, we
      showed that EIN2 gene is required for Pb(II) resistance in Arabidopsis. EIN2 gene
      was induced by Pb(II) treatment, and the ein2-1 mutant showed enhanced
      sensitivity to Pb(II). A higher Pb content was detected in ein2-1 plants than in
      wild-type plants when subjected to Pb(II) treatment, which was associated, at
      least in part, with reduction in expression of AtPDR12 gene, a pump excluding
      Pb(II) and/or Pb(II)-containing toxic compounds from the cytoplasm. Moreover, the
      ein2-1 mutation also impaired glutathione (GSH)-dependent Pb(II) resistance,
      which was related to constitutive reduction of express of GSH1 gene involved in
      GSH synthesis and consequently reduced GSH content. Taken together, all these
      results suggest that EIN2 gene mediates Pb(II) resistance, at least in part,
      through two distinct mechanisms, a GSH-dependent mechanism and a GSH-independent
      AtPDR12-mediated mechanism.

PMID- 19153050
TI  - alpha-l-Arabinofuranosidase from strawberry fruit: cloning of three cDNAs,
      characterization of their expression and analysis of enzymatic activity in
      cultivars with contrasting firmness.
AB  - Softening of fleshy fruits during ripening is associated to catabolism of cell
      wall components. In strawberry, pectin degradation, as well as loss of neutral
      sugars (mainly arabinose), increases during ripening, and probably contributes to
      fruit softening. In this work, we report the activity of alpha-l
      arabinofuranosidase (alpha-l-arafase) and the expression of related genes in
      strawberry. Activity of alpha-l-arafase was measured during ripening of cultivars
      with contrasting firmness. An important increment in the specific activity of
      alpha-l-arafase was detected during ripening in both cultivars. However, in the
      softest one (Toyonoka) the specific activities were higher than in the firmest
      (Camarosa). A combination of semi quantitative reverse transcriptase-PCR (RT-PCR)
      with degenerate primers and a screening of a cDNA library allowed the isolation
      and cloning of three cDNAs encoding putative alpha-l-arafases (FaAra1, FaAra2 and
      FaAra3). The deduced proteins revealed that FaAras belong to the glycoside
      hydrolase family 51 and not to glycoside hydrolase family 3. Expression studies,
      carried out by means of Northern-blot and semi quantitative RT-PCR, revealed that
      FaAras were predominantly expressed in fruit tissue and detected over the entire
      ripening process. Due to similarity of FaAras sequences, Northern-blot analysis
      probably grouped the expression of the three genes. The expression was high at
      small green stage, decreased at white stage and increased thereafter. The
      increment of the expression from white to 50% red stage was more evident in the
      softest cultivar (Toyonoka). Semi quantitative RT-PCR analysis allowed
      determining the expression of individual FaAras. The expression of the three
      genes was detected in all developmental and ripening stages. However, differences
      in expression levels could be detected between cultivars. In the softest
      cultivar, the expression of the three FaAras was higher at 50% and 75% red
      stages, and in the case of FaAra3 a higher expression was found also at 100% red
      stage. Overall, specific activity of alpha-l-arafase was higher in the softest
      cultivar; such activity reflects the expression of at least three putative FaAra
      genes.

PMID- 19153051
TI  - BCL11A represses HBG transcription in K562 cells.
AB  - BCL11A on chromosome 2p16 was recently shown to be a major quantitative trait
      locus for Hb F level and F-cell number in several populations with or without
      beta-hemoglobinopathy. We now show that BCL11A isoforms are expressed in K562
      cells. Butyrate induction of HBG globin production in K562 is associated with
      reduced BCL11A. Conversely, augmented expression of BCL11A in K562 cells through
      transfection of BCL11A expression vector results in more than 50% reduction of
      HBG promoter transcription activity. This transcription repression can be
      abrogated by sodium butyrate. BCL11A binds to GGCCGG motif in nucleotide -56 to 
      51 on the HBG proximal promoter. Together, these data are consistent with BCL11A
      being able to bind to a core motif in the HBG proximal promoter, recruit and
      interact with partners to form a repression complex, leading to deacetylation of
      histones and down-regulation of the HBG transcription.

PMID- 19153052
TI  - A compendium of placebo-controlled trials of the risks/benefits of
      pharmacological treatments for insomnia: the empirical basis for U.S. clinical
      practice.
AB  - For many years practitioners have had limited data from double-blind, placebo
      controlled studies to guide the types of decision-making needed to optimally
      manage patients with insomnia in clinical practice. However, in recent years
      there has been a great increase in insomnia research studies that address issues
      of clinical importance. This body of work represents an increasingly useful
      empirical basis for making clinical practice decisions. The purpose of this
      article is to compile the body of work on the pharmacological management of
      insomnia to make it available in as accessible form as possible for optimal
      application in clinical practice with the hopes that doing so will decrease the
      gap separating the available research and the clinical management of insomnia
      and, thereby, improve the care of the many individuals who suffer from this
      condition. The review of studies consists of the following sections: 1) basic
      pharmacology; 2) double-blind, placebo-controlled trials in adults with primary
      insomnia; 3) double-blind, placebo-controlled trials in elderly patients with
      primary insomnia; 4) adverse effects reported in placebo-controlled trials in
      elderly primary insomnia patients; 5) double-blind, placebo-controlled trials in
      adults and the elderly as a function of treatment duration; 6) double-blind,
      placebo-controlled trials of the treatment of comorbid insomnia. Issues related
      to the application of these data to clinical practice are discussed in the text.

PMID- 19153053
TI  - Narcolepsy in childhood.
AB  - Narcolepsy is a chronic disease commonly diagnosed in middle adulthood. However,
      the first symptoms often appear in childhood and/or adolescence. Pediatric cases
      of narcolepsy are among the most often underrecognised and underdiagnosed
      diseases. This fact raises questions about the reasons for such diagnostic delay
      from the clinical point of view, and what kind of help can be expected from
      auxiliary diagnostic examinations. The aim of the review is to stress some
      specific features of the clinical picture in children, to discuss the role of
      auxiliary examinations at the onset of the disease including sleep studies, tests
      for human leukocyte antigens (HLAs), and cerebrospinal fluid hypocretin (Hcrt)
      measurement, and to draw attention to the most common cases of pediatric
      misdiagnosis. Frequent cataplectic attacks at an early age should lead to
      detailed clinical, neuroimaging and genetic examinations to rule out a secondary
      etiology. Beside the typical symptoms (excessive daytime sleepiness, cataplexy,
      sleep paralysis, hypnagogic/hypnopompic hallucinations), some additional features
      including obesity and nocturnal bulimia can appear. Also poor school performance
      and emotional disorder are common complaints. Treatment should start as early as
      possible to avoid the development of problems with progress at school, and close
      cooperation between school and family should be maintained.

PMID- 19153054
TI  - Mice as potential carriers of infectious bursal disease virus in chickens.
AB  - To investigate the role of mice as potential carriers of infectious bursal
      disease virus (IBDV), three mice were inoculated with a very virulent strain of
      IBDV and allowed to have contact with three uninoculated mice. Faeces, intestine
      and pooled liver and spleen collected from inoculated mice 12 and 24 h post
      inoculation were positive for IBDV by reverse transcriptase-polymerase chain
      reaction (PCR)-nested PCR (RT-PCR-nPCR). IBDV was detected by RT-PCR-nPCR in 3/3
      samples of intestine and 2/3 samples of pooled liver and spleen from uninoculated
      in-contact mice at 24 h after exposure. Chickens developed clinical signs of IBD
      and died when inoculated with faecal extracts prepared from mice 24 h after
      inoculation with IBDV. Bursae were atrophied and positive for IBDV by RT-PCR
      nPCR.

PMID- 19153055
TI  - Discovery of a new biomarker for the mucopolysaccharidoses (MPS), dipeptidyl
      peptidase IV (DPP-IV; CD26), by SELDI-TOF mass spectrometry.
AB  - Surface enhanced laser desorption/ionisation time of flight (SELDI-TOF) mass
      spectrometry has been used to search for new protein biomarkers in the plasma of
      patients with mucopolysacharidoses (MPS). Differences in the levels of some
      plasma proteins, particularly the apolipoprotein ApoCI, were observed between MPS
      patients and normal controls, using the different chromatographic surfaces
      (ProteinChips). ApoCI was identified by both its mass and by immunological
      techniques. In plasma, it exists in two forms, ApoCI and a truncated form which
      lacks two N-terminal amino acids, ApoCI'. In controls, the ratio of ApoCI':ApoCI
      observed using the cation-exchange surface (CM10) was approximately 1:2 whereas
      in most MPS patients it varied from 1:1 to 1:0.8. The ratio of ApoCI':ApoCI in
      plasma is determined by the activity of dipeptidyl peptidase IV, DPP-IV (also
      known as the leucocyte antigen CD26), which was found to be elevated up to 3-fold
      in MPS patients. The DPP-IV activity decreased in MPS I patients undergoing
      enzyme replacement therapy, indicating that it could be a useful biomarker for
      monitoring the efficacy of treatment in MPS disease. As DPP-IV has an important
      regulatory role in metabolism, it is possible that its elevation could cause some
      of the secondary pathology in MPS, and inhibition of DPP-IV might have a role in
      MPS therapy.

PMID- 19153057
TI  - Intensification of sonochemical decolorization of anthraquinonic dye Acid Blue 25
      using carbon tetrachloride.
AB  - In this work, the influence of CCl(4) on the sonochemical decolorization of
      anthraquinonic dye Acid Blue 25 (AB25) in aqueous medium was investigated using
      high frequency ultrasound (1700 kHz). This frequency, reputed ineffective, was
      tested in order to introduce the ultrasound waves with high frequency in the
      field of degradation or removal of dyes from wastewater, due to its limited use
      in this field, and to increase the application of high frequency ultrasound wave
      in the field of environmental protection. The effects of various parameters such
      as the concentration of CCl(4), frequency (22.5 and 1700 kHz), solution pH,
      temperature and tert-butyl alcohol adding on the decolorization rate of AB25 was
      studied. The obtained results clearly demonstrated the significant
      intensification of AB25 decolorization in the presence of CCl(4). The enhancement
      effect of CCl(4) increased by decreasing temperature and by increasing the CCl(4)
      concentration. The pH has a significant influence on the bleaching of dye both in
      the absence and presence of CCl(4). The three investigated dosimeter methods (KI
      oxidation, Fricke reaction and H(2)O(2) production) well corroborate the
      improvement of the sonochemical effects in the presence of CCl(4). The best
      sonochemical decolorization rate of AB25 in aqueous solution both in the absence
      and presence of CCl(4) is observed to occur at 1700 kHz compared to 22.5 kHz. The
      sonochemical oxidation of CCl(4) generates oxidizing species in the liquid phase
      that are highly beneficial for oxidation of hydrophilic and non-volatile
      pollutant, such as dyes, because they are less susceptible to free radical attack
      due to lower stability of the generated free radicals.

PMID- 19153056
TI  - Tuberculosis and HIV: a global menace exacerbated via sex trafficking.
AB  - OBJECTIVE: Global tuberculosis (TB) elimination requires recognition and
      management of TB/HIV co-infected individuals, including those in marginalized
      and/or understudied populations. We sought to examine the prevalence of TB among
      repatriated sex trafficked Nepalese girls and women in whom a high HIV prevalence
      was previously reported. METHODS: We reviewed case records for cases of TB among
      287 sex trafficked girls and women repatriated to a single, rehabilitation non
      governmental organization in Kathmandu, Nepal between 1997 and 2005. TB case
      detection was based on sputum smear results for acid-fast bacilli, radiographs,
      or histories, as reported in medical tests and/or case records. RESULTS: There
      were 17 cases of TB that developed after rescue within the sample of girls and
      women who were aged 7-32 years when they were trafficked. The majority of cases
      (70%) were likely pulmonary TB. Nearly 9 in 10 individuals who developed TB were
      HIV co-infected. CONCLUSIONS: Although preliminary in nature, our findings
      highlight the need for more comprehensive exploration of TB prevalence within sex
      trafficked populations, particularly in light of the large numbers of individuals
      who are sex trafficked in South Asia, the high prevalence of HIV documented in
      this group, and the risk of transmission of TB from and to others.

PMID- 19153058
TI  - Noninvasive in situ identification and band assignments of some pharmaceutical
      excipients inside USP vials with FT-near-infrared spectroscopy.
AB  - For the manufacture of dosage forms all ingredients must be reliably identified.
      In this paper, the suitability of FT-NIR spectroscopy to identify potassium
      sorbate, sodium starch glycollate, calcium ascorbate, calcium carbonate,
      candelilla wax, maltosextrin, monohydrated and anhydrous lactose inside USP vials
      was investigated. Differentiation between the anhydrous and monohydrated forms of
      lactose was found to be possible by studying the regions of the near-infrared
      spectrum corresponding to the combination and first overtone stretching
      frequencies of water. The results show unequivocally the potential of FT-NIR
      spectroscopy for rapid, in situ and non-destructive identification of
      pharmaceutical excipients.

PMID- 19153059
TI  - Attitudes, knowledge and behaviours with regard to skin cancer: a literature
      review.
AB  - In recent years there has been a dramatic increase in the prevalence of skin
      cancer worldwide. There has been a huge amount of research literature on skin
      cancer especially in the last 10-15 years. There is no doubt that this is in
      direct relation to the increases in prevalence of the disease on a worldwide
      basis. Australian and American research has led in the field and again it is
      probable that this has been due to the increase in rates of skin cancer in those
      countries. This paper provides a comprehensive review of the existing
      international literature in the area.

PMID- 19153060
TI  - Evaluation study to ascertain the impact of the clinical academic coaching role
      for enhancing student learning experience within a clinical masters education
      programme.
AB  - AIM: To explore the appropriateness of clinical academic coaching role as a tool
      for enhancing student learning and the development of advanced academic and
      clinical practice skills for nurses. BACKGROUND: Coaching involves a relationship
      between individuals characterised by analyzing and communicating mutually
      understood objectives and motivating others. Coaching is beneficial for
      developing those entering new positions with higher level responsibilities.
      METHOD: A two stage evaluation involved analysis of structured questionnaires
      distributed to students registered for a postgraduate advanced clinical practice
      programme and ten interviews with students and coaches. Data was analysed to
      develop understanding of how coaches were experienced by students as an aid to
      learning. FINDINGS: Data indicates the role supported students through transition
      and provided learning support at crucial times in the academic journey. Specific
      skills and behaviours enhanced the coach-student relationship. The coach's
      understanding of the clinical context was pivotal, as was effective preparation
      to undertake the coaching role. CONCLUSION: Supporting students to make the
      transition into advanced practice roles is a prominent issue within current
      healthcare literature. Clinical coaching enhances learning through a strong and
      coherent partnership between the student, their practice context and the academic
      journey.

PMID- 19153061
TI  - Practice development and the potential for integrating transformational practice
      with research: a response to Editorial: Thompson, D.R., Watson, R., Quinn, T.,
      Worrall-Carter, L., O'Connell, B. 2008. Practice development: what is it and why
      should we be doing it? Nurse Education in Practice 8, 221-222.

PMID- 19153062
TI  - CD4(+)CD25(+)CD127(low/-) regulatory T cells express Foxp3 and suppress effector
      T cell proliferation and contribute to gastric cancers progression.
AB  - Increased populations of regulatory T cells (Tregs) impair anti-tumor immunity.
      Recently, the transcription factor Foxp3 has been reported to play a key role in
      CD4(+)CD25(+) regulatory T cell function and represents a specific marker for
      these cells. However, Foxp3 is a nuclear protein and is of limited value in the
      isolation of Tregs, which is a major reason that many functionally relevant
      aspects of Treg cells are still unknown. Here, we have characterized
      CD4(+)CD25(+)CD127(low/)- as the surface marker of regulatory T cells in gastric
      cancer. 88.1-96.1%of CD25(+)CD127(low/-) T cells expressed Foxp3, the frequency
      of CD4(+)CD25(+)CD127(low/-) regulatory T cells in the peripheral blood of
      gastric cancer patients was significantly higher than that in healthy controls.
      Increased CD4(+)CD25(+)CD127(low/-) regulatory T cells were also present in the
      tumor microenvironment, such as those found in the ascites fluid, tumor tissue or
      adjacent lymph nodes. Particularly those Treg cells associated with the TNM
      stage. In addition, we found that CD4(+)CD25(+)CD127(low/-) Tregs suppressed
      effector T cell proliferation and also correlated to advanced stage of gastric
      cancer. Thus, CD4(+)CD25(+)CD127(low/-) can be used as a selective biomarker to
      enrich human Treg cells and also to perform functional in vitro assays in gastric
      cancer.

PMID- 19153063
TI  - Computed tomography assessment of valvular morphology, function, and disease.
AB  - Recent advancement in computed tomography angiography (CTA) has enabled the
      noninvasive delineation of cardiac valves using this method. Although
      echocardiography is the current standard, CTA is a valuable complementary imaging
      method to evaluate valvular morphology and function. In addition, CTA may
      contribute to the assessment of both congenital and acquired valvular heart
      disease, infectious endocarditis, and postsurgical complications of valve
      replacement.

PMID- 19153064
TI  - Promotion effect of Schisandra nigra on the growth of hair.
AB  - This study was conducted to evaluate the effect of Schisandra nigra, a plant
      native to Jeju Island, South Korea, on the promotion of hair growth. When rat
      vibrissa follicles were treated with 85% ethanol (EtOH) extract of S. nigra, the
      hair-fiber lengths of the vibrissa follicles increased significantly. In
      addition, after topical application of the EtOH extract of S. nigra onto the back
      of C57BL/6 mice every other day, anagen progression of the hair shaft was
      induced. Moreover, the extract increased both the expression of proliferating
      cell nuclear antigen (PCNA) in the bulb matrix region and the proliferation of
      immortalized vibrissa dermal papilla cells. In order to determine the mechanism
      by which S. nigra promotes hair growth, we examined its relationship with the
      transforming growth factor-beta2 (TGF-beta2) signal pathway, which is known to be
      a regulator of catagen induction. When the vibrissa follicles in the anagen phase
      were treated with S. nigra extract for 7 days, the expression of TGF-beta2 in the
      bulb matrix region was found to be lower than that of the control follicles that
      were expected to be in the anagen-catagen transition phase. These results suggest
      that S. nigra extract has the potential to promote hair growth via down
      regulation of TGF-beta2 and the proliferation of dermal papilla.

PMID- 19153065
TI  - Cisplatin-induced acral erythema.

PMID- 19153066
TI  - Efficacy of adalimumab in recalcitrant hidradenitis suppurativa.

PMID- 19153067
TI  - A demodicosis case which responded to systemic ivermectin.

PMID- 19153068
TI  - Promoter methylation status of p15 and p21 genes in HPP-CFCs of bone marrow of
      patients with psoriasis.
AB  - Psoriasis is an inflammatory disease related to dysfunctional immunity. The
      dysfunctional immunity may influence the haematopoietic microenvironment or
      haematopoiesis in psoriasis. However, direct evidence is lacking. Our objective
      was to investigate the proliferation of hematopoietic cells from psoriatic
      patients and any link between the promoter methylation status of p15 and p21
      genes and the colony formation ability of high proliferative potential colony
      forming cells (HPP-CFCs). Marrow mononuclear cells were isolated from the bone
      marrow of psoriatic patients and normal controls by density gradient
      centrifugalization. Colony forming assays of HPP-CFCs were performed in vitro in
      methylcellulose semi-solid culture medium. mRNA expression and the promoter
      methylation status of p15 and p21 genes in HPP-CFCs were studied by semi
      quantitative RT-PCR and methylation-specific PCR respectively. In methycellulose
      semi-solid culture system, the colony count of HPP-CFCs in bone marrow of
      psoriatic patients was significantly less than that of normal controls. Moreover,
      significantly lower positive frequencies of promoter methylation and higher
      transcription levels for p15 and p21 genes were observed in psoriasis in
      comparison to normal volunteers. The lower promoter methylation of p15 and p21
      genes may be an important mechanism for the dysfunctional growth regulation
      pathways in HPP-CFCs in psoriasis.

PMID- 19153069
TI  - Cognitive dysfunction after surgery and anaesthesia: what can we tell the
      grandparents?
AB  - 'Grandpa was never the same after his operation!'. This statement describes a
      myriad of possible clinical difficulties that can afflict older people after
      hospitalisation for major surgery. We summarise the evidence pertaining to the
      phenomenon of Postoperative Cognitive Dysfunction, a condition defined as an
      abnormality on neuropsychological testing, which is said to afflict up to 14% of
      over 70 years olds undergoing elective surgery. So far none of the expected
      surgical, anaesthetic and environmental risk factors have been convincingly
      demonstrated to be responsible for this observed deterioration. While recognising
      the high incidence of the condition as an neuropsychological entity we accept
      that it is difficult to translate this into a reliable estimate of clinical risk
      for the individual patient.

PMID- 19153070
TI  - Therapy-resistant anaemia in congenital nephrotic syndrome of the Finnish type-
      implication of EPO, transferrin and transcobalamin losses.
AB  - Congenital nephrotic syndrome of the Finnish type (CNF) is due to NPHS1 mutation
      and is responsible for a variety of urinary protein losses. We report the case of
      a 4-month-old girl with a particularly severe form (proteinuria approximately 150
      g/l) of CNF. She developed severe non-regenerative anaemia requiring bi-monthly
      blood transfusions despite daily EPO (600 UI/kg) and iron supplementation.
      Epoetin pharmacokinetics revealed a urinary loss of 27% of the given dose within
      the first 24 h after IV injection. However, plasma levels remained increased
      after 24 h (228 UI/l). Plasma transferrin and transcobalamin levels were
      undetectable. Atransferrinaemia and atranscobalaminaemia seem to be responsible
      for disturbed erythropoiesis.

PMID- 19153071
TI  - Dexamethasone enhances basal and TNF-alpha-stimulated production of PAI-1 via the
      glucocorticoid receptor regardless of 11beta-hydroxysteroid dehydrogenase 2
      status in human proximal renal tubular cells.
AB  - BACKGROUND: Long-term treatment with glucocorticoids (GCs) reportedly exaggerates
      renal fibrosis in chronic progressive inflammatory kidney disease. GCs induce the
      gene expression of plasminogen activator inhibitor-1 (PAI-1), a fibrosis enhancer
      in non-renal cells. Tumour necrosis factor-alpha (TNF-alpha) reduces the gene
      expression of 11beta-hydroxysteroid dehydrogenase (HSD) 2, an inactivator of GCs,
      and may enhance GC activity. However, the individual and collective effects of
      adrenal steroids, TNF-alpha and HSD2 status on PAI-1 production are unknown in
      human proximal renal tubular epithelial cells (HPTECs). METHODS: Confluent HPTECs
      were treated with adrenal steroids (10 nM to 10 microM) or TNF-alpha (10 ng/ml)
      for up to 48 h. The mRNA amounts of the target genes were determined by TaqMan
      quantitative PCR, and the PAI-1 protein amounts were measured by an immunoassay.
      RESULTS: Dexamethasone (DXA) maximally increased the amounts of PAI-1 mRNA and
      protein at 100 nM. Aldosterone (Ald) increased PAI-1 expression dose dependently,
      but the effect was over 100-fold weaker than that of DXA. The PAI-1-increasing
      effects of DXA and Ald were abolished completely by U-486, a specific inhibitor
      of the glucocorticoid receptor (GR) but not by spironolactone, a specific
      inhibitor of the mineralocorticoid receptor. The effect of DXA was also blocked
      partially by AG1478 and herbimycin A, tyrosine kinase inhibitors. DXA further
      increased TNF-alpha-stimulated PAI-1 expression via the GR. Although TNF-alpha
      treatment caused an 80% reduction in the gene expression of HSD2, an inactivator
      of GCs, HSD2 inhibition did not enhance DXA-induced PAI-1 production.
      CONCLUSIONS: DXA induces basal and TNF-alpha-stimulated PAI-1 expression via the
      GR pathway, regardless of HSD2 status in HPTECs. Excess GCs may serve as a pro
      fibrotic factor in chronic inflammatory kidney diseases.

PMID- 19153072
TI  - Fine mapping association study and functional analysis implicate a SNP in MSMB at
      10q11 as a causal variant for prostate cancer risk.
AB  - A single nucleotide polymorphism (SNP) at 10q11 (rs10993994) in the 5' region of
      the MSMB gene was recently implicated in prostate cancer risk in two genome-wide
      association studies. To identify possible causal variants in the region, we
      genotyped 16 tagging SNPs and imputed 29 additional SNPs in approximately 65 kb
      genomic region at 10q11 in a Swedish population-based case-control study (CAncer
      of the Prostate in Sweden), including 2899 cases and 1722 controls. We found
      evidence for two independent loci, separated by a recombination hotspot,
      associated with prostate cancer risk. Among multiple significant SNPs at locus 1,
      the initial SNP rs10993994 was most significant. Importantly, using an MSMB
      promoter reporter assay, we showed that the risk allele of this SNP had only 13%
      of the promoter activity of the wild-type allele in a prostate cancer model,
      LNCaP cells. Curiously, the second, novel locus (locus 2) was within NCOA4 (also
      known as ARA70), which is known to enhance androgen receptor transcriptional
      activity in prostate cancer cells. However, its association was only weakly
      confirmed in one of the three additional study populations. The observations that
      rs10993994 is the strongest associated variant in the region and its risk allele
      has a major effect on the transcriptional activity of MSMB, a gene with
      previously described prostate cancer suppressor function, together suggest the T
      allele of rs10993994 as a potential causal variant at 10q11 that confers
      increased risk of prostate cancer.

PMID- 19153073
TI  - Gene-body hypermethylation of ATM in peripheral blood DNA of bilateral breast
      cancer patients.
AB  - Bilaterality of breast cancer is an indicator of constitutional cancer
      susceptibility; however, the molecular causes underlying this predisposition in
      the majority of cases is not known. We hypothesize that epigenetic misregulation
      of cancer-related genes could partially account for this predisposition. We have
      performed methylation microarray analysis of peripheral blood DNA from 14 women
      with bilateral breast cancer compared with 14 unaffected matched controls
      throughout 17 candidate breast cancer susceptibility genes including BRCA1,
      BRCA2, CHEK2, ATM, ESR1, SFN, CDKN2A, TP53, GSTP1, CDH1, CDH13, HIC1, PGR, SFRP1,
      MLH1, RARB and HSD17B4. We show that the majority of methylation variability is
      associated with intragenic repetitive elements. Detailed validation of the tiled
      region around ATM was performed by bisulphite modification and pyrosequencing of
      the same samples and in a second set of peripheral blood DNA from 190 bilateral
      breast cancer patients compared with 190 controls. We show significant
      hypermethylation of one intragenic repetitive element in breast cancer cases
      compared with controls (P = 0.0017), with the highest quartile of methylation
      associated with a 3-fold increased risk of breast cancer (OR 3.20, 95% CI 1.78
      5.86, P = 0.000083). Increased methylation of this locus is associated with lower
      steady-state ATM mRNA level and correlates with age of cancer patients but not
      controls, suggesting a combined age-phenotype-related association. This research
      demonstrates the potential for gene-body epigenetic misregulation of ATM and
      other cancer-related genes in peripheral blood DNA that may be useful as a novel
      marker to estimate breast cancer risk. ACCESSION NUMBERS: The microarray data and
      associated .BED and .WIG files can be accessed through Gene Expression Omnibus
      accession number: GSE14603.

PMID- 19153074
TI  - The SRY-HMG box gene, SOX4, is a target of gene amplification at chromosome 6p in
      lung cancer.
AB  - The search for oncogenes is becoming increasingly important in cancer genetics
      because they are suitable targets for therapeutic intervention. To identify novel
      oncogenes, activated by gene amplification, we analyzed cDNA microarrays by high
      resolution comparative genome hybridization and compared DNA copy number and mRNA
      expression levels in lung cancer cell lines. We identified several amplicons
      (5p13, 6p22-21, 11q13, 17q21 and 19q13) that had a concomitant increase in gene
      expression. These regions were also found to be amplified in lung primary
      tumours. We mapped the boundaries and measured expression levels of genes within
      the chromosome 6p amplicon. The Sry-HMG box gene SOX4 (sex-determining region Y
      box 4), which encodes a transcription factor involved in embryonic cell
      differentiation, was overexpressed by a factor of 10 in cells with amplification
      relative to normal cells. SOX4 expression was also stronger in a fraction of lung
      primary tumours and lung cancer cell lines and was associated with the presence
      of gene amplification. We also found variants of SOX4 in lung primary tumours and
      cancer cell lines, including a somatic mutation that introduced a premature stop
      codon (S395X) at the serine-rich C-terminal domain. Although none of the variants
      increased the transactivation ability of SOX4, overexpression of the wildtype and
      of the non-truncated variants in NIH3T3 cells significantly increased the
      transforming ability of the weakly oncogenic RHOA-Q63L. In conclusion, our
      results show that, in lung cancer, SOX4 is overexpressed due to gene
      amplification and provide evidence of oncogenic properties of SOX4.

PMID- 19153075
TI  - Expression of mutant beta2 nicotinic receptors during development is crucial for
      epileptogenesis.
AB  - Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a focal form of
      epilepsy characterized by seizures occurring during non-REM sleep. We have
      developed and characterized the first mouse model for ADNFLE type III carrying
      the V287L mutation of the beta2 subunit of neuronal nicotinic receptor. Mice
      expressing mutant receptors show a spontaneous epileptic phenotype by
      electroencephalography with very frequent interictal spikes and seizures.
      Expression of the mutant beta2 subunit is driven by a neuronal-specific
      tetracycline-controlled promoter, which allows planned silencing of transgene
      expression in a reversible fashion and tracking the involvement of mutant
      receptor in crucial phases of epileptogenesis. We found that restricted silencing
      during development is sufficient to prevent the occurrence of epileptic seizures
      in adulthood. Our data indicate that mutant nicotinic receptors are responsible
      for abnormal formation of neuronal circuits and/or long-lasting alteration of
      network assembly in the developing brain, thus leading to epilepsy.

PMID- 19153076
TI  - Biocide susceptibility of the Burkholderia cepacia complex.
AB  - OBJECTIVES: The Burkholderia cepacia complex (Bcc) species are important
      opportunistic pathogens with intrinsic antibiotic resistance. They are also well
      known as contaminants of disinfectants, yet their biocide susceptibility has not
      been studied in detail. We investigated Bcc biocide susceptibility and correlated
      it to their taxonomy, antibiotic susceptibility and ability to form biofilms.
      METHODS: Genetically distinct Bcc strains belonging to 12 of the defined species
      were examined. Biocide susceptibility was assessed by (i) broth dilution MIC
      assays, (ii) agar growth-based MBC screens and (iii) suspension tests. Antibiotic
      MIC was determined by Etest strips, and the ability to form biofilms was examined
      in a 96-well plate assay. RESULTS: Biocide susceptibility varied across the Bcc
      complex with high MIC recorded for chlorhexidine (>100 mg/L), cetylpyridinium
      chloride (>200 mg/L), triclosan (>500 mg/L), benzalkonium chloride (>400 mg/L)
      and povidone (>50 000 mg/L). Species-dependent differences were apparent only for
      cetylpyridinium chloride. There was no correlation between biocide susceptibility
      and (i) antibiotic susceptibility or (ii) the ability to form biofilms. Biocide
      MBC was considerably higher than the MIC (chlorhexidine, 6-fold greater;
      cetylpyridinium chloride, 20-fold greater). Cystic fibrosis outbreak strains
      (Burkholderia multivorans Glasgow strain and Burkholderia cenocepacia ET12)
      possessed elevated chlorhexidine resistance, and Bcc bacteria were also shown to
      remain viable in current commercial biocide formulations. CONCLUSIONS: Bcc
      bacteria are resistant to a wide range of biocides and further representatives of
      this group should be included as reference strains in the development of new anti
      infectives and commercial formulations.

PMID- 19153077
TI  - The impact of mental health and traumatic life experiences on antiretroviral
      treatment outcomes for people living with HIV/AIDS.
AB  - Potent antiretroviral therapy (ART) has transformed HIV from a death sentence to
      a chronic illness. Accordingly, the goal of HIV care has shifted from delaying
      death to achieving optimal health outcomes through ART treatment. ART treatment
      success hinges on medication adherence. Extensive research has demonstrated that
      the primary barriers to ART adherence include mental illness, especially
      depression and substance abuse, as well as histories of traumatic experiences
      such as childhood sexual and physical abuse. These psychosocial factors are
      highly prevalent in people living with HIV/AIDS (PLWHA) and predict poor ART
      adherence, increased sexual risk behaviours, ART treatment failure, HIV disease
      progression and higher mortality rates. The efficacy of standard mental health
      interventions, such as antidepressant treatment and psychotherapy, has been well
      defined, and a small but growing body of research demonstrates the potential for
      such interventions to improve ART adherence and reduce sexual risk behaviours.
      Despite this evidence, mental disorders in PLWHA frequently go undiagnosed and
      untreated. Challenges to the provision of mental healthcare for PLWHA in HIV
      clinical settings include time and resource constraints, lack of expertise in
      psychiatric diagnosis and treatment, and lack of available mental health referral
      services. Future research should prioritize the evaluation of mental health
      interventions that are cost-effective and feasible for widespread integration
      into HIV clinical care; the impact of such interventions on ART adherence and
      clinical outcomes; and interventions to identify individuals with histories of
      traumatic experiences and to elucidate the mechanisms through which such
      histories pose barriers to effective HIV treatment.

PMID- 19153078
TI  - Pharmacokinetic evaluation of linezolid in patients with major thermal injuries.
AB  - AIMS: To evaluate the pharmacokinetics of linezolid following its administration
      in patients with major thermal injuries and in a group of healthy volunteers.
      METHODS: In an open-label, multicentre design with two parallel groups, a group
      of patients with major thermal injuries (>20% body area) and a group of age-, sex
      and weight-matched healthy volunteers, subjects received a single 600 mg
      intravenous dose of linezolid. Serial blood and urine collections were made and
      the concentrations of linezolid in these samples were determined by HPLC. Non
      compartmental analyses were used to describe the pharmacokinetic disposition of
      linezolid. RESULTS: C(max) concentrations and the volume of distribution at
      steady state (V(ss)) were not statistically different (P > 0.05) between the two
      groups of subjects. In contrast, values describing clearance [elimination rate
      constant (k(el)), t(1/2) and mean residence time (MRT)] were significantly
      different (P < 0.05) in patients with thermal injuries compared with volunteers,
      which lead to an approximate reduction by half in AUC(0-infinity) from 98.1
      mg.h/L (volunteers) to 42.5 mg.h/L (patients). Although renal clearance was
      similar in the two groups (24.7 +/- 23 versus 30.6 +/- 14.3 mL/min; P = 0.156),
      non-renal clearance was substantially increased (323 +/- 191 versus 80.4 +/- 27.5
      mL/min) in the patients with thermal injuries, though this difference did not
      achieve statistical significance (P = 0.063). CONCLUSIONS: The pharmacokinetics
      of linezolid are altered in patients with major thermal injuries, mainly as a
      result of increased non-renal clearance. These changes are of sufficient
      magnitude that linezolid concentrations may be sub-therapeutic in some patients
      and we suggest that the dosage interval may need to be decreased in this patient
      population.

PMID- 19153079
TI  - Comparison of the pharmacodynamics of imipenem in patients with ventilator
      associated pneumonia following administration by 2 or 0.5 h infusion.
AB  - OBJECTIVES: The aim of this study was to compare the t > MICs of imipenem between
      administration by a 2 h infusion with a 0.5 h infusion. METHODS: The study was a
      randomized three-way crossover in nine patients with ventilator-associated
      pneumonia. Each subject received imipenem in three regimens consecutively: (i) a
      0.5 h infusion of 0.5 g every 6 h for 24 h; (ii) a 2 h infusion of 0.5 g every 6
      h for 24 h; and (iii) a 2 h infusion of 1 g every 6 h for 24 h. RESULTS:
      Following the 0.5 h infusion of 0.5 g of imipenem, the percentages of the t > 4 x
      MICs of 4, 2 and 1 mg/L were 20.32 +/- 9.32%, 44.11 +/- 16.40% and 64.67 +/-
      20.56% of a 6 h interval, respectively. For the 2 h infusion of 0.5 g of
      imipenem, the percentages of the t > 4 x MICs of 4, 2 and 1 mg/L were 17.71 +/-
      19.27%, 53.75 +/- 19.30% and 76.54 +/- 17.36% of a 6 h interval, respectively.
      For the 2 h infusion of 1 g of imipenem, the percentages of the t > 4 x MICs of
      4, 2 and 1 mg/L were 60.26 +/- 23.96%, 77.78 +/- 20.11% and 93.35 +/- 8.26% of a
      6 h interval, respectively. CONCLUSIONS: The 2 h infusions of imipenem resulted
      in greater t > MICs than the 0.5 h infusion. For infections caused by pathogens
      with high MICs, a 2 h infusion of 1 g of imipenem every 6 h can provide plasma
      concentrations above the MIC of 4 mg/L for 60% of a 6 h interval.

PMID- 19153080
TI  - Comparison of the in vitro effects of amoxicillin and ampicillin on the
      polymorphonuclear neutrophil respiratory burst.
AB  - OBJECTIVES: The aim was to compare the in vitro effects of amoxicillin and
      ampicillin on the oxidative metabolism of polymorphonuclear neutrophils (PMNs).
      METHODS: Superoxide radical anion production by PMNs, stimulated or not by
      various exogenous stimulants and in contact with increasing antibiotic
      concentrations, was measured using spectrophotometric methods. RESULTS: Whereas a
      pro-oxidative action of amoxicillin on PMNs was obtained without exogenous
      stimulation or with opsonized zymosan (OZ), the O(2)(-) production by PMNs
      incubated with ampicillin did not increase significantly. CONCLUSIONS: This
      amoxicillin pro-oxidative effect could be due to the activation of the PMN NADPH
      oxidase, to its induction by a membrane effect or via the OZ pathway. It probably
      reinforces amoxicillin intrinsic bactericidal action and might partly explain the
      severe rashes sometimes occurring with amoxicillin treatment.

PMID- 19153081
TI  - A regulatory role of the Bateman domain of IMP dehydrogenase in adenylate
      nucleotide biosynthesis.
AB  - The Bateman domain (CBS subdomain) of IMP dehydrogenase (IMPDH), a rate-limiting
      enzyme of the de novo GMP biosynthesis, is evolutionarily conserved but has no
      established function. Deletion of the Bateman domain has no effect on the in
      vitro IMPDH activity. We report that in vivo deletion of the Bateman domain of
      IMPDH in Escherichia coli (guaB(DeltaCBS)) sensitizes the bacterium to growth
      arrest by adenosine and inosine. These nucleosides exert their growth inhibitory
      effect via a dramatic increase in the intracellular adenylate nucleotide pool,
      which results in the enhanced allosteric inhibition of PRPP synthetase and
      consequently a PRPP deficit. The ensuing starvation for pyrimidine nucleotides
      culminates in growth arrest. Thus, deletion of the Bateman domain of IMPDH
      derepresses the synthesis of AMP from IMP. The growth inhibitory effect of
      inosine can be rescued by second-site suppressor mutations in the genes
      responsible for the conversion of inosine to AMP (gsk, purA, and purB) as well as
      by the prsA1 allele, which encodes a PRPP synthetase that is insensitive to
      allosteric inhibition by adenylate nucleotides. Importantly, the guaB(DeltaCBS)
      phenotype can be complemented in trans by a mutant guaB allele, which encodes a
      catalytically disabled IMPDH(C305A) protein containing an intact Bateman domain.
      We conclude that the Bateman domain of IMPDH is a negative trans-regulator of
      adenylate nucleotide synthesis, and that this role is independent of the
      catalytic function of IMPDH in the de novo GMP biosynthesis.

PMID- 19153082
TI  - Crystal Structures of Human MdmX (HdmX) in Complex with p53 Peptide Analogues
      Reveal Surprising Conformational Changes.
AB  - p53 tumor suppressor activity is negatively regulated through binding to the
      oncogenic proteins Hdm2 and HdmX. The p53 residues Leu(26), Trp(23), and Phe(19)
      are crucial to mediate these interactions. Inhibiting p53 binding to both Hdm2
      and HdmX should be a promising clinical approach to reactivate p53 in the cancer
      setting, but previous studies have suggested that the discovery of dual Hdm2/HdmX
      inhibitors will be difficult. We have determined the crystal structures at 1.3 A
      of the N-terminal domain of HdmX bound to two p53 peptidomimetics without and
      with a 6-chlorine substituent on the indole (which binds in the same subpocket as
      Trp(23) of p53). The latter compound is the most potent peptide-based antagonist
      of the p53-Hdm2 interaction yet to be described. The x-ray structures revealed
      surprising conformational changes of the binding cleft of HdmX, including an
      "open conformation" of Tyr(99) and unexpected "cross-talk" between the Trp and
      Leu pockets. Notably, the 6-chloro p53 peptidomimetic bound with high affinity to
      both HdmX and Hdm2 (K(d) values of 36 and 7 nm, respectively). Our results
      suggest that the development of potent dual inhibitors for HdmX and Hdm2 should
      be feasible. They also reveal possible conformational states of HdmX, which
      should lead to a better prediction of its interactions with potential biological
      partners.

PMID- 19153084
TI  - The effectiveness of a hospital diabetes outreach service in supporting care for
      acutely admitted patients with diabetes.
AB  - BACKGROUND: Patients with diabetes have increased frequency of hospital
      admissions and longer lengths of stay compared to patients without diabetes. Our
      specialist diabetes inpatient service was reconfigured to deliver a proactive
      diabetes outreach service to improve the overall care of this population. AIMS:
      To ascertain the effect of a structured diabetes outreach service to acutely
      admitted patients with diabetes on avoidable admissions, delayed discharges and
      appropriate diabetes related follow-up plans. METHODS: Audits were carried out
      before and 4 months after the introduction of a diabetes outreach service. The
      proportion of patients under care of the diabetes team, avoidable admissions,
      delayed discharges and existence of effective follow-up plans were compared pre-
      and post-implementation of this outreach service. RESULTS: The number of
      inpatients with diabetes fell by 35% (83 on a typical day pre-outreach vs. 53
      post-outreach) despite a similar number of total medical admissions in that month
      (1449 vs.1459). This was due to a reduction in those admitted with diabetes
      related (13 vs. 5) and general medical (29 vs. 10) problems whilst numbers
      requiring other specialist care (41 vs. 39) remained unchanged. The proportion of
      patients under the care of diabetes team rose (23% vs. 73%) while those with
      avoidable admissions (18% vs. 7%), delayed discharges (17% vs. 2%) and
      inappropriate discharge plans (65% vs. 11%) all fell. CONCLUSION: This
      reformatted service was associated with a marked improvement in a number of
      parameters relevant to inpatient care.

PMID- 19153083
TI  - MEK1 binds directly to betaarrestin1, influencing both its phosphorylation by ERK
      and the timing of its isoprenaline-stimulated internalization.
AB  - betaArrestin is a multifunctional signal scaffold protein. Using SPOT immobilized
      peptide arrays, coupled with scanning alanine substitution and mutagenesis, we
      show that the MAPK kinase, MEK1, interacts directly with betaarrestin1. Asp(26)
      and Asp(29) in the N-terminal domain of betaarrestin1 are critical for its
      binding to MEK1, whereas Arg(47) and Arg(49) in the N-terminal domain of MEK1 are
      critical for its binding to betaarrestin1. Wild-type FLAG-tagged betaarrestin1 co
      immunopurifies with MEK1 in HEKB2 cells, whereas the D26A/D29A mutant does not.
      ERK-dependent phosphorylation at Ser(412) was compromised in the D26A/D29A
      betaarrestin1 mutant. A cell-permeable, 25-mer N-stearoylated betaarrestin1
      peptide that encompassed the N-domain MEK1 binding site blocked
      betaarrestin1/MEK1 association in HEK cells and recapitulated the altered
      phenotype seen with the D26A/D29A-betaarrestin1 in compromising the ERK-dependent
      phosphorylation of betaarrestin1. In addition, the MEK disruptor peptide promoted
      the ability of betaarrestin1 to co-immunoprecipitate with endogenous c-Src and
      clathrin, facilitating the isoprenaline-stimulated internalization of the beta(2)
      adrenergic receptor.

PMID- 19153086
TI  - Genes for "Reverse" fruit striping in squash (Cucurbita pepo).
AB  - Longitudinal striping is a common fruit color pattern in Cucurbita pepo and is
      conferred by any of several alleles at the light coloration-1 locus. Normally,
      dark stripes appear over the fruit surface areas between the 10 main subepidermal
      vein tracts with the lighter background color over and adjacent to these vein
      tracts. Less commonly, the striping is "reversed," that is, lighter than the
      background color. The present work was conducted to elucidate the mode of
      inheritance of reverse striping. The results indicated that reverse striping is
      conferred by the complementary interaction of an allele for striping with a
      heretofore unidentified allele at the light coloration-2 locus which is hereby
      designated l-2(R). Fruits of plants carrying an allele for striping and that are
      homozygous for l-2(R) have completely reversed striping, whereas those
      heterozygous for l-2(R) have striping that is completely normal or that is
      partially normal and partially reversed.

PMID- 19153085
TI  - Evolution of microsatellite loci in the adaptive radiation of Hawaiian
      honeycreepers.
AB  - Previous studies have examined germ-line mutations to infer the processes that
      generate and maintain variability in microsatellite loci. Few studies, however,
      have examined patterns to infer processes that act on microsatellite loci over
      evolutionary time. Here, we examine changes in 8 dinucleotide loci across the
      adaptive radiation of Hawaiian honeycreepers. The loci were found to be highly
      variable across the radiation, and we did not detect ascertainment bias with
      respect to allelic diversity or allele size ranges. In examining patterns at the
      sequence level, we found that changes in flanking regions, repeat motifs, or
      repeat interruptions were often shared between closely related species and may be
      phylogenetically informative. Genetic distance measures based on microsatellites
      were strongly correlated with those based on mitochondrial DNA (mtDNA) sequences
      as well as with divergence time up to 3 My. Phylogenetic inferences based on
      microsatellite genetic distances consistently recovered 2 of the 4 honeycreeper
      clades observed in a tree based on mtDNA sequences but differed from the mtDNA
      tree in the relationships among clades. Our results confirm that microsatellite
      loci may be conserved over evolutionary time, making them useful in population
      level studies of species that diverged from the species in which they were
      characterized as long as 5 Ma. Despite this, we found that their use in
      phylogenetic inference was limited to closely related honeycreeper species.

PMID- 19153087
TI  - The Registry of the German Competence NETwork on Atrial Fibrillation: patient
      characteristics and initial management.
AB  - AIMS: The aim of this study was to describe the characteristics of patients with
      atrial fibrillation (AF) enrolled in the Central Registry of the German
      Competence NETwork on Atrial Fibrillation (AFNET) and to assess current medical
      practice in patients treated at various levels of medical care in Germany.
      METHODS AND RESULTS: From February 2004 to March 2006, 9582 ambulatory and
      hospitalized patients with ECG-documented AF were enrolled by 194 participating
      study centres from all levels of medical care in Germany. Clinical type of AF was
      reported as paroxysmal in 2893, persistent in 1873, and permanent in 3134
      patients or classified as a first episode in 1035 patients. Predisposing
      conditions were common and present in 87.6% of the patients. Most patients were
      symptomatic with AF (75.1%). Rhythm control in persistent AF was provided to
      53.4% of the symptomatic patients and to 47.8% of the patients without symptoms.
      Anticoagulation for stroke prevention was given to 71.4% of the patients
      considered eligible by applicable guidelines and to 48.4% of patients with low
      risk where guidelines do not recommend anticoagulation. CONCLUSION: This registry
      provides insight into current medical care of patients with AF in Germany. The
      use of oral anticoagulation in eligible patients was among the highest reported,
      whereas decisions on rate and rhythm control often do not follow current
      recommendations.

PMID- 19153088
TI  - Single-centre use of implantable loop recorders in patients with congenital heart
      disease.
AB  - AIMS: To determine the efficacy of the implantable loop recorder (ILR) in
      patients with congenital heart disease. METHODS AND RESULTS: Retrospective data
      analyses of all patients with congenital heart disease undergoing ILR
      implantation in a congenital cardiac centre. Of 78 ILRs implanted between July
      2000 and October 2007, 22 (15 male) patients had congenital heart disease. The
      median age at implantation was 15.5 years (7.0-46.5). Six patients had
      neurodevelopmental delay. Indications for implantation were syncope (n = 15),
      palpitations (n = 4), and pre-syncope (n = 3). Median implantation time was 19
      months (1-30). Explantation data were available in 16 patients (73%). Implantable
      loop recorders were explanted following establishment of positive diagnosis (n =
      3), negative diagnosis (n = 7), and at the end of battery life (n = 4). One
      patient died with the ILR in situ. One device eroded after 2 months without
      further complication. Following ILR interrogation, diagnosed arrhythmias included
      ventricular tachycardia (n = 2) and sinus node dysfunction (n = 1). On the basis
      of these findings, two patients had intracardiac defibrillators and one patient
      had a dual-chamber pacemaker implanted. CONCLUSION: Implantable loop recorders
      lead to a positive or negative arrhythmic diagnosis following explantation in 71%
      of patients with congenital heart disease. This is particularly beneficial in
      patients with neurodevelopmental delay where accurate history is often limited.

PMID- 19153089
TI  - Genetic aspects of vasovagal syncope: a systematic review of current evidence.
AB  - Knowledge on the aetiology of vasovagal syncope (VVS) is of great importance to
      optimize its diagnostic and therapeutic options. To unravel the largely unknown
      pathophysiology, studies on genetic aspects of VVS can be of use. This systematic
      review on all available literature aims to provide an overview of the current
      knowledge of VVS genetics. The MEDLINE and EMBASE database were systematically
      searched for all studies discussing genetic factors as a cause of VVS. Hereditary
      aspects of VVS were studied in 19 studies. Six studies determined a positive
      family history in, respectively, 19-90% of the VVS patients. These numbers,
      however, are not higher than the cumulative incidence of VVS in the general
      population (35-39%). Four studies examined potential genetic polymorphisms
      associated with VVS. Only a Gly389 allele was more frequently present in VVS
      patients with a positive HUT test, although the significance level was set much
      higher than usual in genetic studies, and this result has not been replicated so
      far. Knowledge on genetic aspects of VVS could be very useful in clinical
      practice and research, but the current evidence that it has a genetic basis is
      not very strong.

PMID- 19153090
TI  - Improving the patient's experience of IVF/ICSI: a proposal for an ovarian
      stimulation protocol with GnRH antagonist co-treatment.
AB  - Patients undergoing IVF/ICSI frequently experience substantial treatment burden,
      risk and psychological distress. These three related elements contribute to a
      negative patient experience that can lead to treatment discontinuation if
      pregnancy is not achieved. One approach to minimize these factors is the use of
      protocols designed to achieve high term, singleton birth rates per IVF treatment
      started, while improving the patient's welfare. Gonadotrophin-releasing hormone
      (GnRH) antagonists may be suitable for inclusion in such a protocol. In clinical
      trial data and meta-analyses, treatment with these agents is associated with
      similar live birth rates but reduced treatment burden (duration and side effects)
      and less risk of ovarian stimulation syndrome, compared with GnRH agonist long
      protocols. GnRH antagonists may also be associated with reduced psychological
      distress compared with agonists, but so far, the evidence for this is
      inconclusive. To facilitate the implementation of treatments that optimize the
      patient's experience, a simple GnRH antagonist protocol for use in predicted
      normal responders is proposed.

PMID- 19153091
TI  - Low-dose aspirin and uterine haemodynamics on the day of embryo transfer in women
      undergoing IVF/ICSI: a randomized, placebo-controlled, double-blind study.
AB  - BACKGROUND: Increased uterine artery (UtA) vascular impedance at the time of
      embryo transfer can decrease implantation and pregnancy rates in women undergoing
      IVF/ICSI. We hypothesized that low-dose aspirin decreases UtA vascular impedance
      on the day of embryo transfer in unselected IVF/ICSI patients when medication is
      started concomitantly with controlled ovarian stimulation. In addition, as
      secondary outcome measures, we investigated whether low-dose aspirin decreases
      the incidence of non-optimal (bilateral UtA PI > or = 3.0) uterine haemodynamics
      and whether it affects arcuate, radial and spiral artery vascular impedances and
      endometrial thickness. METHODS: A total of 122 women who underwent IVF/ICSI were
      randomized to receive 100 mg aspirin (n = 61) or placebo (n = 61) daily, starting
      on the first day of gonadotrophin stimulation. Doppler ultrasonography was
      performed on the day of embryo transfer. RESULTS: Embryo transfer took place in
      57 women in the aspirin group and in 56 women in the placebo group. UtA mean PI
      values did not differ significantly between the groups. The incidence of non
      optimal uterine haemodynamics was lower in the aspirin group than in the placebo
      group (P = 0.03). Other secondary outcome measures did not differ between the
      groups. CONCLUSIONS: In unselected IVF/ICSI women, low-dose aspirin therapy, when
      started concomitantly with controlled ovarian stimulation, did not affect UtA
      vascular impedance on the day of embryo transfer. However, the incidence of non
      optimal uterine haemodynamics was significantly lower in the aspirin group than
      in the placebo group. ClinicalTrials.gov: NCT00683202.

PMID- 19153092
TI  - Assessment of ovarian reserve in adult childhood cancer survivors using anti
      Mullerian hormone.
AB  - BACKGROUND: The aim was to assess possible treatment-induced gonadal damage in a
      cohort of adult female childhood cancer survivors (CCS) using anti-Mullerian
      hormone (AMH), the most sensitive marker of ovarian reserve. METHODS: A total
      cohort of 185 survivors was compared with 42 control subjects. The median follow
      up time was 18.1 years (range 4.1-43.2 year). RESULTS: Median AMH concentrations
      in the analysed cohort were not different from controls (median 1.7 versus 2.1
      microg/l; P = 0.57). However, AMH levels were lower than the 10th percentile of
      normal values in 27% (49/182) of our survivors. In addition, 43% (79/182) had AMH
      levels lower than 1.4 microg/l, a previously established cut-off value which
      predicts ongoing pregnancy after assisted reproduction. There were no differences
      in AMH levels in subgroups classified according to disease. However, survivors
      treated with three or more procarbazine containing chemotherapy cycles had
      significantly lower AMH levels than controls (median 0.5 microg/l; P = 0.004).
      Also survivors treated with abdominal or total body irradiation had significantly
      lower AMH levels than controls (median < 0.1 microg/l; P < 0.001). CONCLUSIONS:
      AMH can be used to identify subgroups of CCS at risk for decreased fertility or
      premature ovarian failure. In these survivors, options for fertility preservation
      should be considered prior to starting treatment since they may be at risk for
      poor chances of pregnancy after assisted reproductive treatment.

PMID- 19153093
TI  - NICE public health guidance: what's new?

PMID- 19153094
TI  - Cochrane Public Health Review Group update: incorporating research generated
      outside of the health sector.

PMID- 19153095
TI  - Association of individual network social capital with abdominal adiposity,
      overweight and obesity.
AB  - BACKGROUND: Limited research has examined the association of individual trust,
      participation and social capital with obesity using objective measures of waist
      circumference (WC), body mass index (BMI) and network measures of social capital.
      METHODS: Data were obtained from a representative sample of Montreal residents.
      Participants completed questionnaires that included a position generator for
      collecting network social capital data. Measures of WC, height and weight were
      collected by registered nurses. To estimate associations with cardiometabolic
      risk, data on WC for individuals with BMI between 18.5 and 34.9 were extracted
      for analysis (n = 291). Using a proportional odds model with clustered robust
      standard errors, we evaluated the association of three different measures of
      individual social capital with elevated and substantially elevated WC and
      overweight and obesity categories of BMI. These measures were then evaluated in
      their associations with elevated WC and BMI, adjusting for socio-demographic and
      behavioral covariates. RESULTS: Network social capital was inversely associated
      with the likelihood of being in an elevated WC risk category (odds ratio (OR) =
      0.81, 95% confidence intervals (CI: 0.69, 0.96) and higher BMI category (OR =
      0.81, 95% CI: 0.71, 0.92). CONCLUSION: Higher individual network social capital
      is associated with a lower likelihood of elevated WC risk and overweight and
      obesity.

PMID- 19153096
TI  - Hospital-acquired infections before and after healthcare reorganization in a
      tertiary university hospital in Norway.
AB  - BACKGROUND: To evaluate hospital-acquired infections (HAIs) in somatic (all
      admissions other than psychiatric) and psychiatric patients admitted to a
      tertiary university hospital in Oslo, before and after reorganization of the
      Norwegian healthcare system in 2002. METHODS: Point prevalence studies were
      conducted four times per annum and over the period from 1995 to 2007. RESULTS: A
      total of 57,360 patients were studied over the whole time period: 80.5% in
      somatic wards and 19.5% in psychiatric wards. The HAI rate was 6.9%, of which
      8.1% were somatic and 1.9% psychiatric. 13.4% of operated patients had HAI,
      including 6.2% due to surgical wound infections. In somatic wards, 0.6-1% were re
      admitted with HAI, 15.2-23% had infections and 18-23% used antibiotics. There was
      a reduction in HAI until 2002. From 2003 on, HAI increased (P = 0.010) in somatic
      wards (P = 0.002), in non-operated patients (P = 0.024) and in extra costs. In
      2002, the Norwegian healthcare system was reorganized. This reorganization led to
      a 30% increase in somatic patients treated from 2003 to 2007 (P = 0.054), 27%
      increase in the total workload per work position (P = 0.024) and 23.5% decrease
      in internal service work. CONCLUSION: A declining trend of HAI was observed from
      1995 to 2002 at the tertiary university hospital in Norway. In 2002, the
      Norwegian healthcare system was reorganized. From 2003 to 2007, HAI increased
      significantly as did the number of somatic patients and workload at our hospital.

PMID- 19153097
TI  - Overexpression of glutamate-cysteine ligase protects human COV434 granulosa
      tumour cells against oxidative and gamma-radiation-induced cell death.
AB  - Ionizing radiation is toxic to ovarian follicles and can cause infertility.
      Generation of reactive oxygen species (ROS) has been implicated in the toxicity
      of ionizing radiation in several cell types. We have shown that depletion of the
      antioxidant glutathione (GSH) sensitizes follicles and granulosa cells to
      toxicant-induced apoptosis and that supplementation of GSH is protective. The
      rate-limiting reaction in GSH biosynthesis is catalysed by glutamate-cysteine
      ligase (GCL), which consists of a catalytic subunit (GCLC) and a regulatory
      subunit (GCLM). We hypothesized that overexpression of Gclc or Gclm to increase
      GSH synthesis would protect granulosa cells against oxidant- and radiation
      induced cell death. The COV434 line of human granulosa tumour cells was stably
      transfected with vectors designed for the constitutive expression of Gclc, Gclm,
      both Gclc and Gclm or empty vector. GCL protein and enzymatic activity and total
      GSH levels were significantly increased in the GCL subunit-transfected cells. GCL
      transfected cells were resistant to cell killing by treatment with hydrogen
      peroxide compared to control cells. Cell viability declined less in all the GCL
      subunit-transfected cell lines 1-8 h after 0.5 mM hydrogen peroxide treatment
      than in control cells. We next examined the effects of GCL overexpression on
      responses to ionizing radiation. ROS were measured using a redox-sensitive
      fluorogenic dye in cells irradiated with 0, 1 or 5 Gy of gamma-rays. There was a
      dose-dependent increase in ROS within 30 min in all cell lines, an effect that
      was significantly attenuated in Gcl-transfected cells. Apoptosis, assessed by
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end
      labelling and activated caspase-3 immunoblotting, was significantly decreased in
      irradiated Gclc-transfected cells compared to irradiated control cells.
      Suppression of GSH synthesis in Gclc-transfected cells reversed resistance to
      radiation. These findings show that overexpression of GCL in granulosa cells can
      augment GSH synthesis and ameliorate various sequelae associated with exposure to
      oxidative stress and irradiation.

PMID- 19153098
TI  - Evaluation of the management of heart failure in primary care.
AB  - BACKGROUND: The extent to which guidelines for the treatment of heart failure are
      currently followed in primary care in the UK is unclear. OBJECTIVE: To evaluate
      the prevalence of heart failure and the pharmacological management of heart
      failure in relation to European Society of Cardiology (ESC) and National
      Institute for Health and Clinical Excellence guidelines. METHODS: Retrospective
      cohort study using routinely collected data from 163 general practices across
      Great Britain contributing data to the Doctors Independent Network (DIN-LINK)
      database over a 5-year period until December 31, 2006. RESULTS: From a patient
      population of nearly 1.43 million, 9311 patients with heart failure were
      identified [mean age 78 years (SD 12)], giving an estimated prevalence of 0.7%.
      Of these, 7410 (79.6%) were prescribed a loop diuretic, 6620 (71.1%) were
      prescribed an angiotensin-converting enzyme (ACE) inhibitor or ARB, 3403 (36.6%)
      were prescribed beta-blockers but only 2732 (29.3%) were prescribed an ACE
      inhibitor or ARB and a beta-blocker in combination. Thirty-five per cent of
      patients prescribed ACE inhibitor and 11.5% of those prescribed beta-blockers met
      ESC guideline target doses. Age, gender and comorbidity predicted whether
      patients received beta-blocker or ACE inhibitor with younger males being more
      likely to receive maximal therapy. CONCLUSIONS: These data suggest that while
      most patients with heart failure receive an ACE inhibitor/ARB in primary care,
      few are titrated to target dose and many do not receive a beta-blocker. Optimum
      treatment appears to be most likely for young men. New strategies are required to
      ensure equitable and optimal treatment for all.

PMID- 19153099
TI  - Currying the heart: curcumin and cardioprotection.
AB  - Curcumin (diferuoylmethane) is the active ingredient of turmeric (curcuma longa).
      There has been a surge of research in its anti-inflammatory and antioxidative
      properties, and its cardiovascular effects. A host of studies in in vitro and in
      vivo models of cardiac injury show that curcumin treatment reduces reactive
      oxygen species generation, monocyte adhesion to activated endothelial cells, and
      phosphorylation of c-Jun N-terminal kinase, p38 mitogen activated protein kinase
      and signal transducer and activator of transcription-3, and subsequent downstream
      signals. These alterations lead to preservation of myocardial function following
      ischemic or biochemical insult to the heart. Recent studies in models of pressure
      overload show that curcumin can reduce cardiac remodeling by altering
      reninangiotensin-system-transforming growth factor beta1 and collagen axis.
      Studies need to be done in humans to define the potential of curcumin in
      limitation of cardiac injury and preservation of cardiac function following
      ischemia.

PMID- 19153100
TI  - CAG repeat polymorphism of the MEF2A gene is not associated with the risk of
      coronary artery disease among Taiwanese.
AB  - A 21-bp deletion mutation of the exon 11 of the myocyte enhancer factor-2A
      (MEF2A) gene was shown to cause familial coronary artery disease. This finding
      raises the possibility that MEF2A variants may contribute to the risk of coronary
      artery disease. In total, 258 patients with coronary artery disease and 258
      controls were analyzed for the MEF2A variants. The analysis revealed that all
      patients were negative for Pro279Leu and 21-bp deletion mutations in exons 7 and
      11, respectively. The distribution of the allele frequencies of MEF2A exon 11 CAG
      repeat (CAG)n polymorphism was similar in both patients and controls; Further, no
      significant association was noted between MEF2A exon 11 (CAG)n polymorphism and
      the risk of myocardial infarction. Our data suggest that there is no evidence of
      an association between the MEF2A exon 11 (CAG)n polymorphism and the risk of
      coronary artery disease/myocardial infarction in the Chinese population in
      Taiwan.

PMID- 19153101
TI  - The association of active and passive smoking with peripheral arterial disease:
      results from NHANES 1999-2004.
AB  - We aim to quantify the association between different forms of tobacco use and
      peripheral arterial disease (PAD) and to characterize the association between
      secondhand smoke exposure and PAD in a large nationally representative sample of
      the US population. We observed significant associations between current and
      former cigarette smoking and PAD. The association between noncigarette forms of
      tobacco and PAD was not significant even after adjustment for clinical and
      demographic variables. Secondhand smoke was not significantly associated with
      PAD. Interestingly, a ;;threshold phenomenon'' for tobacco exposure was
      demonstrated for PAD occurrence. Individuals with serum cotinine >155 ng/ mL were
      at significantly higher risk of having PAD as compared with a nonexistent or a
      minimal risk below this threshold value. Lack of association between PAD and
      secondhand smoke exposure in conjunction with the threshold phenomenon described
      above leads us to speculate existence of striking differences between the
      systemic circulation and lower extremity vasculature in terms of pathogenesis of
      atherosclerosis.

PMID- 19153102
TI  - Observations of a magnetic microstructure in a Co-CoO obliquely evaporated tape
      using electron holography.
AB  - The magnetic microstructure in a Co-CoO obliquely evaporated tape that was
      subjected to a recording bit length of 250 nm was studied using electron
      holography. The reconstructed phase image demonstrated a periodic pattern of
      magnetic flux loops that were inclined to the film normal due to a well-developed
      columnar structure. When a magnetic field was applied to the tape for observing
      the remanent state by holography, the periodic pattern of the flux loops
      gradually disappeared. Interestingly, on applying a large magnetic field, the
      contour lines in the reconstructed phase image became approximately parallel to
      the longitudinal axis of the sliced tape, i.e. the contour lines were made to
      virtually deviate from the easy magnetization axis. The observations were
      supported by a computer simulation in which the effect of the stray magnetic
      field was considered.

PMID- 19153104
TI  - Autoantibody profiling in patients with very early rheumatoid arthritis: a follow
      up study.
AB  - OBJECTIVE: To investigate time courses of autoantibody profiles in patients with
      early arthritis. PATIENTS AND METHODS: A total of 200 patients with very early
      arthritis (<3 months duration), among them 102 patients with a final diagnosis of
      rheumatoid arthritis (RA) and 98 with other rheumatic diseases, were followed up
      for several years. First follow-up testing was performed in all patients (mean 5
      months from baseline), and 82 patients with RA and 35 patients without RA were
      available for last follow-up testing (mean 32 months from baseline). IgM
      rheumatoid factor (RF) was measured by nephelometry, IgA-RF, IgG-RF and anti
      cyclic citrullinated peptide antibodies (ACPA) by ELISA, and anti-RA33 antibodies
      were determined by immunoblotting. RESULTS: At baseline, IgA-RF was detectable in
      29% and IgG-RF in 14% of patients with RA while IgM-RF>50 IU/ml (RF50) was
      positive in 45% of the patients; specificities were 97%, 99% and 96%,
      respectively. However, the vast majority of patients positive for IgA-RF or IgG
      RF were also positive for RF50 or ACPA. During follow-up, the prevalence of ACPA
      slightly increased while prevalence of all RF subtypes and anti-RA33 decreased.
      Remarkably, the number of patients positive for RF50 and/or ACPA remained
      constant, and these patients had a highly increased risk for developing erosive
      disease in contrast to patients solely positive for anti-RA33. CONCLUSIONS:
      Testing for RF subtypes did not provide additional diagnostic information.
      Patients positive for RF50 and/or ACPA had an unfavourable prognosis,
      irrespectively of changes in the antibody profile during follow-up, whereas anti
      RA33 positivity was inversely associated with erosiveness at baseline and at
      later time points.

PMID- 19153103
TI  - Junctional adhesion molecule-A is abnormally expressed in diffuse cutaneous
      systemic sclerosis skin and mediates myeloid cell adhesion.
AB  - OBJECTIVE: To investigate the role of junctional adhesion molecule-A (JAM-A) in
      the pathogenesis of systemic sclerosis (SSc). METHODS: Biopsy specimens from
      proximal and distal arm skin and serum were obtained from patients with SSc and
      normal volunteers. To determine the expression of JAM-A on SSc dermal fibroblasts
      and in SSc skin, cell surface ELISAs and immunohistology were performed. An ELISA
      was designed to determine the amount of soluble JAM-A (sJAM-A) in serum. Myeloid
      U937 cell-SSc dermal fibroblast and skin adhesion assays were performed to
      determine the role of JAM-A in myeloid cell adhesion. RESULTS: The stratum
      granulosum and dermal endothelial cells (ECs) from distal arm SSc skin exhibited
      significantly decreased expression of JAM-A in comparison with normal volunteers.
      However, sJAM-A was increased in the serum of patients with SSc compared with
      normal volunteers. Conversely, JAM-A was increased on the surface of SSc compared
      with normal dermal fibroblasts. JAM-A accounted for a significant portion of U937
      binding to SSc dermal fibroblasts. In addition, JAM-A contributed to U937
      adhesion to both distal and proximal SSc skin. CONCLUSIONS: JAM-A expression is
      dysregulated in SSc skin. Decreased expression of JAM-A on SSc ECs may result in
      a reduced response to proangiogenic basic fibroblast growth factor. Increased JAM
      A expression on SSc fibroblasts may serve to retain myeloid cells, which in turn
      secrete angiogenic factors.

PMID- 19153105
TI  - Animal models and potential mechanisms of plaque destabilisation and disruption.
AB  - Studies of the pathophysiological mechanism of both acute coronary syndromes and
      plaque stabilising treatment are driving the development of animal models of
      vulnerable plaque. In contrast to advances in human studies of pathology, the
      definition, criteria and classification of vulnerable and ruptured plaques in
      animal models are still in dispute. Many approaches to increasing the intrinsic
      vulnerability of plaques or extrinsic forces on plaques have been reported.
      However, an ideal animal model mimicking human plaque rupture is still lacking,
      and the exact cellular and molecular mechanisms of plaque progression are not
      fully understood. This review summarises current progress in animal model studies
      related to plaque destabilisation and disruption and the possible mechanisms
      involved.

PMID- 19153106
TI  - Feature binding in the feedback layers of area V2.
AB  - The visual features of an object are processed by multiple, functionally
      specialized areas of cerebral cortex. When several objects are seen
      simultaneously, what mechanism preserves the association of features that belong
      to a single item? We address this question-known as the "binding problem"-by
      examining combinatorial feature selectivity of neurons in area V2. In recording
      from anesthetized macaques, we estimate that dual selectivity for chromatic and
      spatiotemporal attributes is 50% more common (27% vs. 18% sampling frequency) in
      superficial and deep layer neurons receiving feedback connections from higher
      areas, compared with layer 4-3 neurons relaying ascending signals. The operation
      of feedback pathways is thought to mediate attentional modulation of activity
      that may achieve binding through acting to select one single object for higher
      representation and filtering out competing objects. We propose that dual
      selective neurons perform a "bridging" function, mediating the transfer of
      feedback-induced bias between feature dimensions. The bias can be propagated
      through V2 output neurons (of unitary selectivity) to higher levels of
      specialized processing and so promote selection of the target object's
      representation among multiple feature maps. The bridging function would thus act
      to unify the outcome of parallel, object-selective processes taking place along
      segregated visual pathways.

PMID- 19153108
TI  - The brain's intention to imitate: the neurobiology of intentional versus
      automatic imitation.
AB  - Whenever we observe a movement of a conspecific, our mirror neuron system becomes
      activated, urging us to imitate the observed movement. However, because such
      automatic imitation is not always appropriate, an inhibitive component keeping us
      from imitating everything we see seems crucial for an effective social behavior.
      This becomes evident from neuropsychological conditions like echopraxia, in which
      this suppression is absent. Here, we unraveled the neurodynamics underlying this
      proposed inhibition of automatic imitation by measuring and manipulating brain
      activity during the execution of a stimulus-response compatibility paradigm.
      Within the identified connectivity network, right middle/inferior frontal cortex
      sends neural input concerning general response inhibition to right premotor
      cortex, which is involved in automatic imitation. Subsequently, the fully
      prepared imitative response is sent to left opercular cortex that functions as a
      final gating mechanism for intentional imitation. We propose an informed
      neurocognitive model of inhibition of automatic imitation, suggesting a
      functional dissociation between automatic and intentional imitation.

PMID- 19153107
TI  - Mapping the regulator of G protein signaling 4 (RGS4): presynaptic and
      postsynaptic substrates for neuroregulation in prefrontal cortex.
AB  - Regulator of G protein signaling 4 (RGS4) regulates intracellular signaling via G
      proteins and is markedly reduced in the prefrontal cortex (PFC) of patients with
      schizophrenia. Characterizing the expression of RGS4 within individual neuronal
      compartments is thus key to understanding its actions on individual G protein
      coupled receptors (GPCRs). Here we present an ultrastructural reference map of
      RGS4 protein in macaque PFC based on immunogold electron microscopic analysis. At
      the soma, all labeling was asynaptic and affiliated with subsurface cistern
      microdomains of pyramidal neurons. The nucleus displayed most of
      immunoreactivity. RGS4 levels were particularly high along proximal apical
      dendrites and markedly decreased with distance from the soma; clustered label was
      present at the bifurcation into second-order branches. In distal dendrites and in
      spines, the protein was found flanking or directly facing the postsynaptic
      density of symmetric and asymmetric synapses. Axons also expressed RGS4. In fact,
      the density and distribution of pre- and postsynaptic labeling was correlated
      with the axon ultrastructure and the type of established synapses. The data
      indicate that RGS4 is strategically positioned to regulate not only postsynaptic
      but also presynaptic signaling in response to synaptic and nonsynaptic GPCR
      activation, having broad yet highly selective influences on multiple aspects of
      PFC cellular physiology.

PMID- 19153110
TI  - What men who have sex with men think about the human papillomavirus vaccine.
AB  - This study aimed to ascertain the attitudes of men who have sex with men (MSM) to
      the human papillomavirus (HPV) vaccine and to determine the age at which MSM
      would be willing to ask for the HPV vaccine in relation to their age of sexual
      debut. Of 205 MSM attending the Melbourne Sexual Health Centre between December
      2007 and January 2008, 200 (98%; median age 27 years) completed the study
      questionnaire. Only 30% were aware that there was a vaccine available for
      protection against infection with certain HPV types. When informed of the
      increased risk of anal cancer among MSM, 47% of MSM indicated that they would be
      willing to pay $A450 for the vaccine course. A total of 93% indicated that they
      would be willing to disclose that they were MSM to a health professional in order
      to obtain the vaccine for free, but not until a median age of 20 years: 2 years
      after the median age of sexual debut (18 years) and after a median of 15 sexual
      partners. If the HPV vaccine is targeted to MSM, the challenge will be for MSM to
      be vaccinated before they acquire HPV infection.

PMID- 19153109
TI  - A case-control study on occupational risk factors for sino-nasal cancer.
AB  - OBJECTIVES: Sino-nasal cancer has been consistently associated with exposure to
      wood dust, leather dust, nickel and chromium compounds; for other occupational
      hazards, the findings are somewhat mixed. The aim of this study was to
      investigate the risk of sino-nasal epithelial cancer (SNEC) by histological type
      with prior exposure to suspected occupational risk factors and, in particular,
      those in metalworking. METHODS: Between 1996 and 2000, incident cases were
      collected on a monthly basis from hospitals throughout the Piedmont region of
      Italy by the regional Sino-nasal Cancer Registry. A questionnaire on occupational
      history, completed by 113 cases and 336 hospital controls, was used to assign
      exposure to occupational hazards. The relationship between SNEC and cumulative
      exposure to these hazards was explored using unconditional logistic regression to
      statistically adjust for age, sex, smoking and co-exposures, allowing for a 10
      year latency period. RESULTS: The risk of adenocarcinoma was significantly
      increased with ever-exposure to wood dust (odds ratio; OR = 58.6), and to leather
      dust (OR = 32.8) and organic solvents (OR = 4.3) after controlling for wood dust,
      whereas ever-exposure to welding fumes (OR = 3.7) and arsenic (OR = 4.4)
      significantly increased the risk for squamous cell carcinoma. For each of these
      hazards, a significant increasing trend in risk across ordered cumulative
      exposure categories was found and, except for arsenic, a significantly increased
      risk with ever-exposure at low intensity. Treating cumulative exposure on a
      continuous scale, a significant effect of textile dusts was also observed for
      adenocarcinoma. For a mixed group of other histological types, a significant
      association was found with wood dust and organic solvents. CONCLUSIONS: Some
      occupational risk factors for SNEC were confirmed, and dose-response
      relationships were observed for other hazards that merit further investigation.
      The high risk for adenocarcinoma with low-intensity exposure to wood dust lends
      support for a reduction in the occupational threshold value.

PMID- 19153111
TI  - Activity and safety of a prolonged daily schedule of zoledronic acid in a patient
      with bone metastases from urothelial carcinoma.

PMID- 19153112
TI  - Docetaxel 100 versus 80 mg/m2 as adjuvant treatments of early breast cancer: an
      exploratory analysis of a randomised trial.

PMID- 19153113
TI  - High-resolution lymphoscintigraphy is essential for recognition of the
      significance of internal mammary nodes in breast cancer.
AB  - BACKGROUND: Sentinel node biopsy (SNB) of internal mammary nodes (IMNs) in breast
      cancer is controversial. Most centers rarely identify IMN on lymphoscintigraphy
      but others report up to 45% of cases. Controversy relates to the technique of
      lymphatic mapping, safety of IMN SNB, the significance of positive IMN, and
      potential to impact survival. METHODS: Assessment of drainage rates from two
      unrelated nuclear medicine departments' databases. Review of related literature.
      RESULTS: High-resolution lymphoscintigraphy results in IMN drainage in one-third
      of breast cancers. There is a learning curve for the technique. In 1754
      consecutive cases, internal mammary drainage occurred in 53% of medial tumors,
      37% midline tumors and 24% of lateral tumors (overall 34%). Extended radical
      mastectomy series also demonstrate the (approximately) 1/3 ratio when comparing
      IMN positivity rates to axillary node positivity rates (18.8% : 48.3%) and in
      node-positive patients (31% : 100%). The management altering potential of IMN
      assessment and potential survival impact are discussed. CONCLUSIONS: IMN mapping
      gives information that alters management in up to one-third of cases. These rates
      of IMN drainage are reproducible and reflect lymphatic density and anatomy of the
      breast. A priority need exists to establish a collaborative clinical trial to
      clarify the value of IMN assessment.

PMID- 19153114
TI  - Osteosarcoma in adolescents and adults: survival analysis with and without lung
      metastases.
AB  - BACKGROUND: Survival data are still limited and controversial about adult
      patients with osteosarcoma as older group of patients has mostly been excluded
      from the historical trials. PATIENTS AND METHODS: Patients with osteosarcoma,
      from 1986 to 2003, in a single center, were reviewed. Survival according to a
      cutoff age of 40 was studied. Patients with lung metastases were identified.
      Variables at first lung involvement including time to first lung metastases,
      multiplicity and size of the metastatic lesions and use of chemotherapy were all
      analyzed. RESULTS: A total of 247 patients, with age range of 14-77 years, were
      reviewed. Five-year survival is 66% with no difference between patients <40 or
      >or=40 years. Eighty-five patients, with either synchronous or metachronous lung
      involvement, have 3-year postlung metastases survival (PLMS) of 30%. Forty-seven
      patients (55.3%) underwent lung resection with 3-year PLMS of 38% compared with
      16% for nonoperated patients (P = 0.00023). Patients who developed lung
      metastases within a year and have fewer than four lung lesions have better PLMS
      (P < 0.0001 for both). CONCLUSIONS: Older patients have identical survival to
      pediatric population and should have a similar management approach. Complete
      metastectomy is the key issue for prolonged survival. Time to lung metastases and
      number of lung lesions are the most important prognostic factors.

PMID- 19153115
TI  - Combination of surgery and chemotherapy and the role of targeted agents in the
      treatment of patients with colorectal liver metastases: recommendations from an
      expert panel.
AB  - The past 5 years have seen the clear recognition that the administration of
      chemotherapy to patients with initially unresectable colorectal liver metastases
      can increase the number of patients who can undergo potentially curative
      secondary liver resection. Coupled with this, recent data have emerged that show
      that perioperative chemotherapy confers a disease-free survival advantage over
      surgery alone in colorectal cancer (CRC) patients with initially resectable liver
      disease. The purpose of this paper is to build on the existing knowledge and
      review the issues surrounding the use of chemotherapy +/- targeted agents
      combined with surgery in the treatment of CRC patients with liver metastases,
      with a view to providing clinical recommendations. An international panel of 21
      experts in colorectal oncology comprising liver surgeons and medical oncologists
      reviewed the available evidence. In a major change to clinical practice, the
      panel's recommendation was that the majority of patients with CRC liver
      metastases should be treated up front with chemotherapy, irrespective of the
      initial resectability status of their metastases.

PMID- 19153116
TI  - Efficacy of FOLFIRI-3 (irinotecan D1,D3 combined with LV5-FU) or other irinotecan
      based regimens in oxaliplatin-pretreated metastatic colorectal cancer in the
      GERCOR OPTIMOX1 study.
AB  - BACKGROUND: Second-line irinotecan-based chemotherapy is commonly used in
      metastatic colorectal cancers after first-line oxaliplatin-based chemotherapy. No
      standard schedule of irinotecan has been established in this situation. PATIENTS
      AND METHODS: Metastatic colorectal cancer patients included in the OPTIMOX1 phase
      III study received first-line oxaliplatin-based chemotherapy (FOLFOX). No second
      line was defined in the protocol, but data concerning second line were
      prospectively registered. Inclusion criterion was patients receiving an
      irinotecan-based second-line chemotherapy. Second-line progression-free survival
      (PFS) and tumor response were evaluated according to type of irinotecan-based
      regimen administered. RESULTS: A total of 342 patients received irinotecan-based
      chemotherapy as second-line chemotherapy: FOLFIRI-3 [n = 109, irinotecan 100
      mg/m(2) days 1 and 3 combined with leucovorin (LV) 400 mg/m(2) day 1 and 46-h
      continuous 5-fluorouracil (5-FU) 2000 mg/m(2)], FOLFIRI-1 (n = 112, irinotecan
      180 mg/m(2) day 1 combined with LV 400 mg/m(2) day 1, 5-FU bolus 400 mg/m(2) and
      46-h continuous 5-FU 2400 mg/m(2)) and other various irinotecan-based regimens (n
      = 121). Median second-line PFS was 3.0 months (FOLFIRI-3: 3.7 months; FOLFIRI-1:
      3.0 months; other regimens: 2.3 months). In multivariate analysis, FOLFIRI-3
      regimen (relative risk 0.43, 95% confidence interval 0.28-0.68, P = 0.0003) and
      lactate deshydrogenase level at inclusion (P = 0.0006) in OPTIMOX1 were
      associated with a longer second-line PFS. CONCLUSION: In unselected patients
      pretreated with oxaliplatin, PFS in second line appeared to be improved by
      FOLFIRI-3 regimen.

PMID- 19153117
TI  - High coexpression of both insulin-like growth factor receptor-1 (IGFR-1) and
      epidermal growth factor receptor (EGFR) is associated with shorter disease-free
      survival in resected non-small-cell lung cancer patients.
AB  - BACKGROUND: Insulin-like growth factor receptor-1 (IGFR-1) represents a novel
      molecular target in non-small-cell lung cancer (NSCLC). IGFR-1 and epidermal
      growth factor receptor (EGFR) activation is essential to mediate tumor cell
      survival, proliferation and invasion. We explored the correlation between IGFR-1
      and EGFR, their relationship with clinicopathological parameters and their impact
      on outcome in resected stage I-III NSCLC patients. PATIENTS AND METHODS: Tumors
      from 125 surgical NSCLC patients were evaluated for IGFR-1 and EGFR expression by
      immunohistochemistry. Kaplan-Meier estimates of survival and time to recurrence
      were calculated for clinical variables and biologic markers using the Cox model
      for multivariate analysis. RESULTS: IGFR-1 protein overexpression was detected in
      36.0% of NSCLC patients and was associated with larger tumor size (P = 0.04) but
      not with other clinical or biological characteristics. EGFR protein
      overexpression was observed in 55.2% of NSCLC, more frequently in squamous cell
      carcinoma (SCC) than non-SCC (63.7% versus 36.3%, chi(2) = 9.8, P = 0.001). IGFR
      1 protein expression was associated with EGFR protein expression (P = 0.03). At
      the multivariate analysis, high coexpression of both IGFR-1 and EGFR was a
      significant prognostic factor of worse disease-free survival (DFS) (hazard ratio
      2.51, P = 0.01). CONCLUSION: A statistically significant association was observed
      between high coexpression of both IGFR-1 and EGFR and worse DFS in early NSCLC
      patients.

PMID- 19153118
TI  - Expert opinion on the use of anthracyclines in patients with advanced breast
      cancer at cardiac risk.
AB  - Anthracyclines are considered to be among the most active agents for the
      treatment of breast cancer. However, their use is limited by cumulative, dose
      related cardiotoxicity. Such cardiotoxicity results in a permanent loss of
      cardiac myocytes and a progressive reduction in cardiac function following each
      subsequent dose of anthracycline. Initially, damage to the heart is subclinical;
      however, increasingly impaired cardiac function can result in cardiovascular
      symptoms, with serious cardiac injury resulting in chronic heart failure. Since
      the early detection and treatment of cardiotoxicity can reduce its clinical
      effects, it is important that oncologists are aware of these adverse effects and
      manage them appropriately. This review examines the risk factors for
      anthracycline-associated cardiotoxicity and offers recommendations on strategies
      to reduce the cardiotoxicity of anthracyclines in the management of patients with
      advanced breast cancer.

PMID- 19153119
TI  - The antidiabetic drug metformin: a pharmaceutical AMPK activator to overcome
      breast cancer resistance to HER2 inhibitors while decreasing risk of
      cardiomyopathy.

PMID- 19153120
TI  - Pharmacokinetics of sunitinib in an obese patient with a GIST.

PMID- 19153121
TI  - Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in
      patients with advanced gastric cancer: a randomised phase III noninferiority
      trial.
AB  - BACKGROUND: To compare capecitabine/cisplatin with 5-fluorouracil/cisplatin as
      first-line treatment for advanced gastric cancer (AGC). PATIENTS AND METHODS: In
      this randomised, open-label, phase III study, patients received cisplatin (80
      mg/m(2) i.v. day 1) plus oral capecitabine (1000 mg/m(2) b.i.d., days 1-14) (XP)
      or 5-FU (800 mg/m(2)/day by continuous infusion, days 1-5) (FP) every 3 weeks.
      The primary end point was to confirm noninferiority of XP versus FP for
      progression-free survival (PFS). RESULTS: A total of 316 patients were randomised
      to XP (n = 160) or FP (n = 156). In the per-protocol population, median PFS for
      XP (n = 139) versus FP (n = 137) was 5.6 versus 5.0 months. The primary end point
      was met with an unadjusted hazard ratio (HR) of 0.81 [95% confidence interval
      (CI) 0.63-1.04, P < 0.001 versus noninferiority margin of 1.25]. Median overall
      survival was 10.5 versus 9.3 months for XP versus FP (unadjusted HR = 0.85, 95%
      CI 0.64-1.13, P = 0.008 versus noninferiority margin of 1.25). The most common
      treatment-related grade 3/4 adverse events in XP versus FP patients were as
      follows: neutropenia (16% versus 19%), vomiting (7% versus 8%), and stomatitis
      (2% versus 6%). CONCLUSIONS: XP showed significant noninferiority for PFS versus
      FP in the first-line treatment of AGC. XP can be considered an effective
      alternative to FP.

PMID- 19153122
TI  - Phase II study with oxaliplatin and S-1 for patients with metastatic colorectal
      cancer.
AB  - BACKGROUND: To evaluate the efficacy and safety of the combination of oxaliplatin
      and S-1 (OS) in treating metastatic colorectal cancer. PATIENTS AND METHODS:
      Eligible patients were those with measurable lesions, no previous history of
      chemotherapy (except adjuvant chemotherapy), an age of 18-70 years, and an
      Eastern Cooperative Oncology Group performance status of zero to two. Oxaliplatin
      130 mg/m(2) was administered i.v. on day 1, and S-1 40 mg/m(2) b.i.d. was
      administered orally on days 1-14, every 3 weeks. RESULTS: Forty-eight patients
      (median age, 56 years) were enrolled: 23 had colon cancer, seven rectosigmoid
      colon cancer; and 18 rectal cancer. Of the 48 patients, 31 were diagnosed with
      metastatic cancer and 17 had relapsed cancer after surgery, with adjuvant
      chemotherapy or chemoradiotherapy. In total, 413 cycles were administered (median
      6 per patient; range 2-24). Toxicity was evaluated in 48 patient and response in
      46. Major toxic effects were grade 3/4 thrombocytopenia (13%) and neutropenia
      (10%). The overall response rate was 54% [95% confidence interval (CI) 40% to
      68%]. The median time to progression and median survival time were 8.5 (95% CI
      6.2-10.9) months and 27.2 (95% CI 20.3-34.0) months, respectively. CONCLUSIONS:
      These data indicate that the OS regimen is effective and well tolerated in
      patients with advanced colorectal cancer.

PMID- 19153123
TI  - Prognostic nomogram for predicting the 5-year probability of developing
      metastasis after neo-adjuvant chemotherapy and definitive surgery for AJCC stage
      II extremity osteosarcoma.
AB  - BACKGROUND: In this retrospective study, we developed and internally validate a
      nomogram for predicting 5-year metastasis probability for nonmetastatic extremity
      osteosarcoma. PATIENTS AND METHODS: We reviewed 365 osteosarcoma patients treated
      at our institute from 1990 to 2003. Clinicopathologic variables were recorded.
      Multivariate analysis using Cox proportional hazards regression was done and this
      Cox model was used as the basis for the nomogram. RESULTS: By American Joint
      Committee on Cancer (AJCC) staging system, 141 patients (38.6%) were stage IIA
      and 224 (61.4%) were stage IIB. Multivariate Cox model identified patient age at
      diagnosis, tumor size, humeral location, and tumor necrosis rate after
      chemotherapy as correlated with metastasis-free survival. The degree of
      contribution of each covariate to the total point was tumor location, tumor
      necrosis rate, maximal tumor diameter, and age in decreasing order. The
      concordance index for the model was 0.78. Nomogram discrimination was superior to
      that of AJCC stage (concordance index 0.78 versus 0.68; P = 0.02) and histologic
      response grouping (concordance index 0.78 versus 0.69; P = 0.0004). CONCLUSIONS:
      We devised a nomogram for nonmetastatic osteosarcoma that proposes improved
      estimates of metastasis over AJCC staging system or tumor necrosis rate. We
      suggest that this nomogram allows individualized risk assessments and could be
      used as the basis for risk-adapted therapy.

PMID- 19153125
TI  - Re-evaluation of the prolactin receptor expression in human breast cancer.
AB  - The pituitary hormone PRL is involved in tumorigenesis in rodents and humans. PRL
      promotes proliferation, survival and migration of cancer cells acting via the PRL
      receptor (PRLR). Aiming to perform a large-scale immunohistochemical (IHC)
      screening of human mammary carcinomas for PRLR expression, we evaluated the
      specificity of commercially available anti-human PRLR antibodies (B6.2, U5, PRLRi
      pAb, 1A2B1, 250448 and H-300). The latter three antibodies were found to
      specifically recognise PRLR. The relative PRLR expression level detected with
      these antibodies closely reflected the level of (125)I-PRL binding to the cell
      surface. The monoclonal antibody (mAb) 250448 was specific for the N
      ()glycosylated form of PRLR and blocked PRL binding and signalling. The PRLRi
      polyclonal antibody recognised cytokeratin-18. The mAb B6.2, previously used in a
      number of studies, was found to lack specificity for PRLR and to rather recognise
      a PRLR-associated protein. The mAb U5 raised against the rat PRLR did not cross
      react with the human receptor. Only one mAb, 1A2B1, was found useful for
      detection of PRLR in IHC applications. This antibody recognised PRLR expressed in
      human breast cancer cell lines and decidual cells in tissue sections of human
      placenta. Screening of 160 mammary adenocarcinomas demonstrated significant
      immunoreactivity in only four tumours, indicating that PRLR is generally not
      strongly upregulated in human breast cancer. However, even a very low level of
      PRLR expression was found to be sufficient to mediate PRL responsiveness in
      breast cancer cell lines.

PMID- 19153124
TI  - Phase II trial of the farnesyltransferase inhibitor tipifarnib plus fulvestrant
      in hormone receptor-positive metastatic breast cancer: New York Cancer Consortium
      Trial P6205.
AB  - BACKGROUND: Fulvestrant produces a clinical benefit rate (CBR) of approximately
      45% in tamoxifen-resistant, hormone receptor (HR)-positive metastatic breast
      cancer (MBC) and 32% in aromatase inhibitor (AI)-resistant disease. The
      farnesyltransferase inhibitor tipifarnib inhibits Ras signaling and has
      preclinical and clinical activity in endocrine therapy-resistant disease. The
      objective of this study was to determine the efficacy and safety of tipifarnib
      fulvestrant combination in HR-positive MBC. PATIENTS AND METHODS: Postmenopausal
      women with no prior chemotherapy for metastatic disease received i.m. fulvestrant
      250 mg on day 1 plus oral tipifarnib 300 mg twice daily on days 1-21 every 28
      days. The primary end point was CBR. RESULTS: The CBR was 51.6% [95% confidence
      interval (CI) 34.0% to 69.2%] in 31 eligible patients and 47.6% (95% CI 26.3% to
      69.0%) in 21 patients with AI-resistant disease. A futility analysis indicated
      that it was unlikely to achieve the prespecified 70% CBR. Tipifarnib dose
      modification was required in 8 of 33 treated patients (24%). CONCLUSIONS: The
      target CBR of 70% for the tipifarnib-fulvestrant combination in HR-positive MBC
      was set too high and was not achieved. The 48% CBR in AI-resistant disease
      compares favorably with the 32% CBR observed with fulvestrant alone in prior
      studies and merit further clinical and translational evaluation.

PMID- 19153126
TI  - FDA allows drug firms to distribute journal articles about unapproved uses.

PMID- 19153128
TI  - Definitive characterisation of adrenal lesions.

PMID- 19153131
TI  - Symptom burden and quality of life in end-stage renal disease: a study of 179
      patients on dialysis and palliative care.
AB  - Palliative care for end-stage renal disease (ESRD) is developing in Hong Kong.
      This is the first local study to explore the symptom burden and quality of life
      (QOL) of ESRD patients on chronic dialysis and palliative care. This was a
      prospective cross-sectional study conducted on ESRD patients in a hospital in
      Hong Kong from January 2006 to April 2007. Data collected included demographics,
      socioeconomic status, modified Charlson Comorbidity Index (CCI), prevalence and
      intensity of 23 ESRD-related symptoms as rated by numerical rating scale (0-10),
      Brief Pain Inventory and QOL by MOS SF-36. A total of 179 ESRD patients completed
      the study; 45 patients (25.1%) were in the palliative care group and 134 patients
      (74.9%) in the dialysis group. The palliative care group were older (73.1 +/- 7.1
      vs 58.2 +/- 11.4 years, P < 0.001), had marginally higher modified CCI (8.5 +/-
      1.9 vs 6.1 +/- 2.4, P = 0.05), had more diabetics (62.2 vs 35.8%, P < 0.001) and
      were of poorer socioeconomic status than the dialysis group. The mean number of
      symptoms was 8.2 +/- 3.9 and 9.3 +/- 4.7 in the palliative care and the dialysis
      group, respectively (P = NS). Fatigue, cold aversion, pruritus, lower torso
      weakness and difficulty sleeping were the five most prevalent symptoms in both
      groups, and were also among the most intense symptoms. QOL was significantly
      impaired in both groups. Scores of all QOL domains correlated negatively with the
      number of symptoms (P < 0.001). Our ESRD patients under palliative care and
      dialysis had overlapping symptom prevalence and intensity, significant symptom
      burden and impaired QOL.

PMID- 19153132
TI  - Assessment of iron status and the role for iron-replacement therapy in anaemic
      cancer patients under the care of a specialist palliative care unit.
AB  - Anaemia is common in advanced cancer, may develop for several reasons, and is not
      always symptomatic. Our observations of the seemingly indiscriminate prescription
      of iron-replacement therapy (IRT) for anaemic palliative care patients, and our
      practice of discontinuing IRT in patients with normal red-cell indices, prompted
      a study to determine (1) the prevalence of anaemia in our patients, (2) what
      proportion had iron deficiency, (3) the prevalence and benefits of IRT and (4)
      the prevalence of side effects attributable to IRT. The prevalence of anaemia was
      65%. We found a 9% prevalence of iron deficiency, and suggestive but inconclusive
      evidence of iron deficiency in a further 41%, but only three (27%) of these
      patients had typical iron deficiency red-cell indices. Only two patients within
      the study population were taking IRT. Haemoglobin increased significantly in one,
      but fell in the other, and both experienced side effects attributable to iron.
      IRT should neither be indiscriminately prescribed nor withheld for anaemic
      palliative care patients, and the decision should not be based on red-cell
      indices alone. When symptomatic anaemia is found in patients whose general
      condition indicates that IRT would be acceptable, iron status should be fully
      assessed. A therapeutic trial of IRT may be justified where ferritin is elevated,
      but other parameters suggest iron deficiency.

PMID- 19153129
TI  - Publication guidelines for quality improvement studies in health care: evolution
      of the SQUIRE project.
AB  - In 2005 we published draft guidelines for reporting studies of quality
      improvement, as the initial step in a consensus process for development of a more
      definitive version. The current article contains the revised version, which we
      refer to as standards for quality improvement reporting excellence (SQUIRE). This
      narrative progress report summarises the special features of improvement that are
      reflected in SQUIRE, and describes major differences between SQUIRE and the
      initial draft guidelines. It also briefly describes the guideline development
      process; considers the limitations of and unresolved questions about SQUIRE;
      describes ancillary supporting documents and alternative versions under
      development; and discusses plans for dissemination, testing, and further
      development of SQUIRE.

PMID- 19153133
TI  - The existential impact of starting corticosteroid treatment as symptom control in
      advanced metastatic cancer.
AB  - Treatment with corticosteroids often results in increased appetite, reduced
      nausea and improved well-being in patients with advanced metastatic cancer.
      Therefore, we have studied the existential impact of starting corticosteroid
      treatment as symptom control in this patient group using qualitative content
      analysis with both a descriptive and an interpretative focus. Ten patients were
      interviewed before and after 1 week of treatment with 4 mg betamethasone. Prior
      to treatment, patients reported distressing symptoms, deterioration and
      diminished autonomy, symbolising threat and death. Corticosteroid treatment
      produced symptom relief in the majority of the patients. They reported enhanced
      physical abilities and experienced feelings of a more normalized life and
      strengthened autonomy, symbolising health and hope. This transfer from threat to
      hope has important existential consequences in end-of-life care and should be
      addressed when communicating goals of treatment and care with the patient and
      family.

PMID- 19153134
TI  - FrameDP: sensitive peptide detection on noisy matured sequences.
AB  - SUMMARY: Transcriptome sequencing represents a fundamental source of information
      for genome-wide studies and transcriptome analysis and will become increasingly
      important for expression analysis as new sequencing technologies takes over array
      technology. The identification of the protein-coding region in transcript
      sequences is a prerequisite for systematic amino acid-level analysis and more
      specifically for domain identification. In this article, we present FrameDP, a
      self-training integrative pipeline for predicting CDS in transcripts which can
      adapt itself to different levels of sequence qualities. AVAILABILITY: FrameDP for
      Linux (web-server and underlying pipeline) is available at
      {{http://iant.toulouse.inra.fr/FrameDP}} for direct use or a standalone
      installation.

PMID- 19153135
TI  - The protein-small-molecule database, a non-redundant structural resource for the
      analysis of protein-ligand binding.
AB  - MOTIVATION: An enabling resource for drug discovery and protein function
      prediction is a large, accurate and actively maintained collection of
      protein/small-molecule complex structures. Models of binding are typically
      constructed from these structural libraries by generalizing the observed
      interaction patterns. Consequently, the quality of the model is dependent on the
      quality of the structural library. An ideal library should be non-biased and
      comprehensive, contain high-resolution structures and be actively maintained.
      RESULTS: We present a new protein/small-molecule database (the PSMDB) that offers
      a non-redundant set of holo PDB complexes. The database was designed to allow
      frequent updates through a fully automated process without manual annotation or
      filtering. Our method of database construction addresses redundancy at both the
      protein and the small-molecule level. By efficiently handling structures with
      covalently bound ligands, we allow our database to include a larger number of
      structures than previous methods. Multiple versions of the database are available
      at our web site, including structures of split complexes--the proteins without
      their binding ligands and the non-covalently bound ligands within their native
      coordinate frame. AVAILABILITY: http://compbio.cs.toronto.edu/psmdb

PMID- 19153136
TI  - Sequence-based prediction of protein interaction sites with an integrative
      method.
AB  - MOTIVATION: Identification of protein interaction sites has significant impact on
      understanding protein function, elucidating signal transduction networks and drug
      design studies. With the exponentially growing protein sequence data, predictive
      methods using sequence information only for protein interaction site prediction
      have drawn increasing interest. In this article, we propose a predictive model
      for identifying protein interaction sites. Without using any structure data, the
      proposed method extracts a wide range of features from protein sequences. A
      random forest-based integrative model is developed to effectively utilize these
      features and to deal with the imbalanced data classification problem commonly
      encountered in binding site predictions. RESULTS: We evaluate the predictive
      method using 2829 interface residues and 24,616 non-interface residues extracted
      from 99 polypeptide chains in the Protein Data Bank. The experimental results
      show that the proposed method performs significantly better than two other
      sequence-based predictive methods and can reliably predict residues involved in
      protein interaction sites. Furthermore, we apply the method to predict
      interaction sites and to construct three protein complexes: the DnaK molecular
      chaperone system, 1YUW and 1DKG, which provide new insight into the sequence
      function relationship. We show that the predicted interaction sites can be
      valuable as a first approach for guiding experimental methods investigating
      protein-protein interactions and localizing the specific interface residues.
      AVAILABILITY: Datasets and software are available at
      http://ittc.ku.edu/~xwchen/bindingsite/prediction.

PMID- 19153137
TI  - Commentary: Is structural equation modelling a step forward for epidemiologists?

PMID- 19153138
TI  - A self-cleaving DNA enzyme modified with amines, guanidines and imidazoles
      operates independently of divalent metal cations (M2+).
AB  - The selection of modified DNAzymes represents an important endeavor in expanding
      the chemical and catalytic properties of catalytic nucleic acids. Few examples of
      such exist and to date, there is no example where three different modified bases
      have been simultaneously incorporated for catalytic activity. Herein, dCTP, dATP
      and dUTP bearing, respectively, a cationic amine, an imidazole and a cationic
      guanidine, were enzymatically polymerized on a DNA template for the selection of
      a highly functionalized DNAzyme, called DNAzyme 9-86, that catalyzed (M(2+))
      independent self-cleavage under physiological conditions at a single
      ribo(cytosine)phosphodiester linkage with a rate constant of (0.134 +/- 0.026)
      min(-1). A pH rate profile analysis revealed pK(a)'s of 7.4 and 8.1, consistent
      with both general acid and base catalysis. The presence of guanidinium cations
      permits cleavage at significantly higher temperatures than previously observed
      for DNAzymes with only amines and imidazoles. Qualitatively, DNAzyme 9-86
      presents an unprecedented ensemble of synthetic functionalities while
      quantitatively it expresses one of the highest reported values for any self
      cleaving nucleic acid when investigated under M(2+)-free conditions at 37 degrees
      C.

PMID- 19153139
TI  - Dissecting the splicing mechanism of the Drosophila editing enzyme; dADAR.
AB  - In Drosophila melanogaster, the expression of adenosine deaminase acting on RNA
      is regulated by transcription and alternative splicing so that at least four
      different isoforms are generated that have a tissue-specific splicing pattern.
      Even though dAdar has been extensively studied, the complete adult expression
      pattern has yet to be elucidated. In the present study, we investigate mature
      transcripts of dAdar arising from different promoters. Two predominant isoforms
      of dAdar are expressed in gonads and dAdar is transcribed from both the embryonic
      and the adult promoters. Furthermore, full-length transcripts containing the
      alternatively spliced exon-1 are expressed in a tissue-specific manner. The
      splicing factor B52/SRp55 binds within the alternative spliced exon 3a and plays
      a role in this alternative splicing event.

PMID- 19153140
TI  - Generation of single-chain LAGLIDADG homing endonucleases from native homodimeric
      precursor proteins.
AB  - Homing endonucleases (HEs) cut long DNA target sites with high specificity to
      initiate and target the lateral transfer of mobile introns or inteins. This high
      site specificity of HEs makes them attractive reagents for gene targeting to
      promote DNA modification or repair. We have generated several hundred
      catalytically active, monomerized versions of the well-characterized homodimeric
      I-CreI and I-MsoI LAGLIDADG family homing endonuclease (LHE) proteins.
      Representative monomerized I-CreI and I-MsoI proteins (collectively termed mCreIs
      or mMsoIs) were characterized in detail by using a combination of biochemical,
      biophysical and structural approaches. We also demonstrated that both mCreI and
      mMsoI proteins can promote cleavage-dependent recombination in human cells. The
      use of single chain LHEs should simplify gene modification and targeting by
      requiring the expression of a single small protein in cells, rather than the
      coordinate expression of two separate protein coding genes as is required when
      using engineered heterodimeric zinc finger or homing endonuclease proteins.

PMID- 19153141
TI  - Functional links between clustered microRNAs: suppression of cell-cycle
      inhibitors by microRNA clusters in gastric cancer.
AB  - microRNAs (miRNAs) play integral roles in diverse processes including
      tumorigenesis. miRNA gene loci are often found in close conjunction, and such
      clustered miRNA genes are transcribed from a common promoter to generate
      polycistronic primary transcript. The primary transcript (pri-miRNA) is then
      processed by two RNase III proteins to release the mature miRNAs. Although it has
      been speculated that the miRNAs in the same cluster may play related biological
      functions, this has not been experimentally addressed. Here we report that the
      miRNAs in two clusters (miR-106b approximately 93 approximately 25 and miR-222
      approximately 221) suppress the Cip/Kip family members of Cdk inhibitors
      (p57(Kip2), p21(Cip1) and p27(Kip1)). We show that miR-25 targets p57 through the
      3'-UTR. Furthermore, miR-106b and miR-93 control p21 while miR-222 and miR-221
      regulate both p27 and p57. Ectopic expression of these miRNAs results in
      activation of Cdk2 and facilitation of G1/S phase transition. Consistent with
      these results, both clusters are abnormally upregulated in gastric cancer tissues
      compared to the corresponding normal tissues. Ectopic expression of miR-222
      cluster enhanced tumor growth in the mouse xenograft model. Our study
      demonstrates the functional associations between clustered miRNAs and further
      implicates that effective cancer treatment may require a combinatorial approach
      to target multiple oncogenic miRNA clusters.

PMID- 19153142
TI  - The genetic influence on radiographic osteoarthritis is site specific at the
      hand, hip and knee.
AB  - OBJECTIVE: To identify whether a shared genetic influence accounts for the
      occurrence of OA at different skeletal sites. METHODS: Multivariate modelling of
      data on prevalent radiographic OA at the hand (DIP, PIP and CMC joints), hip and
      knee joints assessed in 992 monozygotic and dizygotic female twin participants
      from the TwinsUK Registry. RESULTS: OA at all the five joint sites was heritable.
      Genetic influences were strongly correlated among joints in the hand; however,
      there was little evidence of common genetic pathways to account for the co
      occurrence of OA at the hand, hip and knee. CONCLUSIONS: While genetic influences
      are important in explaining the variation in occurrence of OA at the hand, hip
      and knee, there is no evidence that common or shared genetic factors determine
      the occurrence of disease across all these skeletal sites. The findings suggest
      that there are important aetiological differences in the disease that are site
      specific in women. These results have implications for the design of studies
      examining the genetic basis of OA as well as for strategies aimed at preventing
      and treating the disease.

PMID- 19153143
TI  - Safety of combination therapy with rituximab and etanercept for patients with
      rheumatoid arthritis.

PMID- 19153144
TI  - Employment and work disability in systemic lupus erythematosus: a systematic
      review.
AB  - OBJECTIVES: Many studies have provided information on employment and work
      disability (WD) rates in patients with SLE, yet are often limited by small sample
      sizes, poor generalizability or fail to examine the risks and outcomes of WD. Our
      objective was to systematically review the literature on WD in SLE to identify a
      more generalizable point estimate and range of WD in SLE patients. METHODS: A
      search was conducted using Medline, EMBase, PubMed and Cochrane databases to
      identify publications related to SLE and employment and/or WD. Characteristics of
      the study samples and employment/WD data were extracted. Descriptive statistics,
      a test for heterogeneity and random effects models were performed to obtain
      pooled estimates of employment and WD rates for all patients. RESULTS: Twenty-six
      studies with a total of 9886 SLE patients were found; however, not all patients
      were reviewed for WD. Larger studies demonstrated the prevalence of WD at 20-40%,
      and pooled estimates found that 46% (95% CI 40%, 52%) were employed with SLE and
      34% (95% CI 24%, 44%) had WD. WD was related to psychosocial and disease-related
      factors including age, race, socioeconomic status (SES), education, disease
      activity and duration, pain, fatigue, anxiety and neurocognitive involvement.
      CONCLUSIONS: This study provides strong evidence that costs of SLE may be very
      high due to job loss at a younger age in SLE patients, and identifies some risk
      factors associated with WD, which should be targeted by interventions aimed at
      preventing job loss.

PMID- 19153145
TI  - Circulating endothelial cells and rheumatoid arthritis: relationship with plasma
      markers of endothelial damage/dysfunction.
AB  - OBJECTIVES: RA is associated with endothelial cell dysfunction (ECD) and
      increased cardiovascular mortality and morbidity. Circulating endothelial cells
      (CECs) are a novel marker of severe endothelial damage. We hypothesized altered
      CECs in patients with RA compared with community controls (CCs) and hospital
      controls (HCs, with diabetes and hypertension) correlate with established plasma
      markers of inflammation and of ECD. METHODS: CECs (CD146-immunobeads), von
      Willebrand factor, soluble E-selectin, soluble intercellular adhesion molecule-1,
      soluble vascular endothelial adhesion molecule-1 (sVCAM, all ELISA) and C
      reactive protein (CRP, immunonephelometry) were measured in 57 patients with RA,
      45 CC and 23 HC patients. RESULTS: CECs in RA [median/interquartile range 8 (5
      13.5) cells/ml] were elevated compared with either CC [4 (2-8.5) cells/ml] or HC
      [4 (1-8) cells/ml] (both P < 0.001). Levels of CECs did not correlate with other
      markers of ECD or of inflammation but did correlate inversely with sVCAM.
      CONCLUSION: Evidence of endothelial damage in the form of mildly increased
      numbers of CECs is present in RA and is independent of plasma markers of
      inflammation and of ECD.

PMID- 19153146
TI  - Comment on: The use of MRI in early RA.

PMID- 19153147
TI  - Decreased binding of the D3 dopamine receptor-preferring ligand [11C]-(+)-PHNO in
      drug-naive Parkinson's disease.
AB  - The D(3) dopamine (DA) receptor is a member of the D(2)-like DA receptor family.
      While the D(2) receptor is abundant especially in motor-regions of the striatum,
      the D(3) receptor shows a relative abundance in limbic regions and globus
      pallidus. This receptor is of current interest in neurology because of its
      potential involvement in psychiatric and motor complications in Parkinson's
      disease and the possibility that dopamine D(3)-preferring agonist therapy might
      delay progression of the disorder. Preclinical data indicate that striatal levels
      of the D(3) (but not the D(2)) DA receptor are decreased following lesion of
      nigrostriatal DA neurons; at present, there are no in vivo data on this receptor
      subtype in Parkinson's disease. The objective of this positron emission
      tomography study was to compare [(11)C]-(+)-PHNO (D(3) versus D(2) preferring)
      and [(11)C]raclopride (D(3) = D(2)) binding in brain of non-depressed, non
      demented, dopaminergic drug-naive patients with early-stage Parkinson's disease
      (n = 10), relative to matched-controls (n = 9). Parkinson's disease was
      associated with a trend for bilaterally decreased [(11)C]-(+)-PHNO (but not
      [(11)C]raclopride) binding in the D(3)-rich ventral striatum (-11%, P = 0.07) and
      significantly decreased binding in globus pallidus (-42%, P = 0.02). In contrast,
      in the primarily D(2)-populated putamen, both [(11)C]-(+)-PHNO (25%, P = 0.02)
      and [(11)C]raclopride (25%, P < 0.01) binding were similarly increased,
      especially on the side contra-lateral to the symptoms. In the midbrain,
      presumably containing D(3) receptors localized to the substantia nigra, [(11)C]
      (+)-PHNO binding was normal. Decreased [(11)C]-(+)-PHNO to [(11)C]raclopride
      ratio correlated with motor deficits and lowered-mood (P < 0.02). Our imaging
      data suggest that brain DA neuron loss in the human causes region-specific
      differential changes in DA D(2) and D(3) receptors with D(3) receptor
      'downregulation' possibly related to some motor and mood problems in Parkinson
      disease. D(3) receptor levels might be a determinant vulnerability factor
      underlying side-effects associated with treatment; hence, these initial findings
      provide valuable baseline information to understand the role of D(3) receptors in
      response to Parkinson's disease medication.

PMID- 19153148
TI  - Neurological practice in the Centuriae of Amatus Lusitanus.
AB  - Amatus Lusitanus, a Portuguese Jew who gained notoriety as one of the most famous
      physician-scientists in XVI century Europe published collections of case
      histories--Centuriae--describing his most interesting patients. The Renaissance
      was a transitional period for medicine and the neurological sciences, which if
      still dominated by the humoral and ventricular-pneumatic doctrines, were taking
      the first steps away from them. We analysed the Centuriae for neurological and
      psychiatric cases in order to appreciate neurological practice in this period and
      selected one hundred which fit those diagnostic categories. The Centuriae contain
      cases of CNS infection and trauma, epilepsy, apoplexy and depressed states of
      consciousness (including coma, carus, lethargy and cataphora), headache and
      vertigo, tumours, cranial nerve paralysis, melancholy, anatomical and
      physiological observations, as well as a short treatise on cranial traumatology.
      The most relevant observations point to the importance of the brain parenchyma in
      cognition, provide original observations of epidemic lethargic encephalitis,
      describe the neurological consequences of syphilis, including the first
      description of tertiary syphilis, attempt to distinguish mania from melancholy,
      extensively describe medical and surgical treatment of cranial trauma, document
      the first use of anatomical dissection to study a case of brain abscess, negate
      Galen's view of the optic nerves as hollow, and describe the use of new drugs
      such as guaiac wood for the treatment of headache. The Centuriae not only provide
      insight into neurological clinical practice in the XVI century, but also
      emphasize the role of Amatus Lusitanus as an important precursor of this
      discipline, given his numerous original observations.

PMID- 19153149
TI  - Early seizure frequency and aetiology predict long-term medical outcome in
      childhood-onset epilepsy.
AB  - In clinical practice, it is important to predict as soon as possible after
      diagnosis and starting treatment, which children are destined to develop
      medically intractable seizures and be at risk of increased mortality. In this
      study, we determined factors predictive of long-term seizure and mortality
      outcome in a population-based cohort of 102 children. At the end of the 40-year
      median follow-up, since their first seizure before the age of 16 years, 95 (93%)
      of 102 patients had entered one or more one-year remissions (1YR). In contrast, 7
      (7%) patients never experienced any 1YR and their epilepsy was considered drug
      resistant. Two factors present early in the course of treatment were found to be
      associated with adverse outcome. Having weekly seizures during the first year of
      treatment carried an 8-fold risk [hazard ratio 8.2 (1.6-43.0), P = 0.0125] of
      developing drug resistant epilepsy and a 2-fold risk of never entering terminal
      1YR [hazard ratio 2.7 (1.5-5.0), P = 0.0010]. Having weekly seizures prior to
      treatment only slightly increased the risk to never enter terminal 1YR [hazard
      ratio 1.7 (1.04-2.9), P = 0.0350]. Thirteen of 102 patients (13%) died during
      follow-up. Long-term mortality was 9-fold higher for patients with symptomatic
      epilepsy [hazard ratio 9.0 (1.8-44.8), P = 0.0071]. Mortality was not, however,
      increased by having weekly seizures prior to or during the first year of
      treatment versus fewer seizures. Early seizure frequency can predict long-term
      seizure control during antiepileptic drug treatment, but not mortality.
      Aetiology, however, is predictive of both seizure outcome and mortality in
      childhood-onset epilepsy. Using these criteria allows early identification of
      children destined to develop intractable epilepsy and increased mortality.

PMID- 19153150
TI  - Neural correlates of motor dysfunction in children with traumatic brain injury:
      exploration of compensatory recruitment patterns.
AB  - Traumatic brain injury (TBI) is a common form of disability in children.
      Persistent deficits in motor control have been documented following TBI but there
      has been less emphasis on changes in functional cerebral activity. In the present
      study, children with moderate to severe TBI (n = 9) and controls (n = 17) were
      scanned while performing cyclical movements with their dominant and non-dominant
      hand and foot according to the easy isodirectional (same direction) and more
      difficult non-isodirectional (opposite direction) mode. Even though the children
      with TBI were shown to be less successful on various items of a clinical motor
      test battery than the control group, performance on the coordination task during
      scanning was similar between groups, allowing a meaningful interpretation of
      their brain activation differences. fMRI analysis revealed that the TBI children
      showed enhanced activity in medial and anterior parietal areas as well as
      posterior cerebellum as compared with the control group. Brain activation
      generally increased during the non-isodirectional as compared with the
      isodirectional mode and additional regions were involved, consistent with their
      differential degree of difficulty. However, this effect did not interact with
      group. Overall, the findings indicate that motor impairment in TBI children is
      associated with changes in functional cerebral activity, i.e. they exhibit
      compensatory activation reflecting increased recruitment of neural resources for
      attentional deployment and somatosensory processing.

PMID- 19153151
TI  - Live imaging of Toll-like receptor 2 response in cerebral ischaemia reveals a
      role of olfactory bulb microglia as modulators of inflammation.
AB  - Activation of microglial cells in response to ischaemic injury, inflammatory
      and/or immune stimuli is associated with the marked induction of Toll-like
      receptor 2 (TLR2). At present, little is known about the spatial and temporal
      sequence of events, micro-regional specificities and the potential long term role
      of the TLR2 response to brain injuries. To investigate microglial activation/TLR2
      response in real time, we generated a transgenic mouse model bearing the dual
      reporter system luciferase/green fluorescent protein under transcriptional
      control of a murine TLR2 promoter. In this model, transcriptional activation of
      TLR2 was visualized in the brains of live animals using
      biophotonic/bioluminescence molecular imaging and a high resolution/sensitivity
      charged coupled device camera. It was found that TLR2 induction/microglial
      activation has a marked chronic component after ischaemic injury and may last
      several months after the initial attack. The pro-inflammatory response was not
      restricted to the site of ischaemic injury but was also evident in the olfactory
      bulb. A significant TLR2 response was first seen in the olfactory bulb 6 h after
      stroke and several hours before the increase in photon emission over the site of
      infarction. This sequence of events was further confirmed by
      immunohistochemistry. A similar early TLR2 response from olfactory bulb microglia
      was observed in the brain's immune response to pathogens. We therefore propose
      that, owing to their unique situation, receiving and translating numerous inputs
      from the brain as well as from the environment, olfactory bulb microglia may
      serve as sensors and/or modulators of brain inflammation.

PMID- 19153152
TI  - Cholinergic modulation of the cerebral metabolic response to citalopram in
      Alzheimer's disease.
AB  - Pre-clinical and human neuropharmacological evidence suggests a role of
      cholinergic modulation of monoamines as a pathophysiological and therapeutic
      mechanism in Alzheimer's disease. The present study measured the effects of
      treatment with the cholinesterase inhibitor and nicotinic receptor modulator,
      galantamine, on the cerebral metabolic response to the selective serotonin
      reuptake inhibitor, citalopram. Seven probable Alzheimer's disease patients and
      seven demographically comparable controls underwent two positron emission
      tomography (PET) glucose metabolism scans, after administration of a saline
      placebo infusion (Day 1) and after citalopram (40 mg, IV, Day 2). The scan
      protocol was repeated in the Alzheimer's disease patients 2 months after
      titration to a 24 mg galantamine dose. At baseline, cerebral glucose metabolism
      was reduced in Alzheimer's disease patients relative to controls in right middle
      temporal, left posterior cingulate and parietal cortices (precuneus and inferior
      parietal lobule), as expected. Both groups demonstrated acute decreases in
      cerebral glucose metabolism after citalopram to a greater extent in the
      Alzheimer's disease patients. In the patients, relative to the controls,
      citalopram decreased glucose metabolism to a greater extent in middle frontal
      gyrus (bilaterally), left middle temporal gyrus and right posterior cingulate
      prior to treatment. Galantamine treatment alone increased metabolism in the right
      precuneus, right inferior parietal lobule and right middle occipital gyrus. In
      contrast, during galantamine treatment, citalopram increased metabolism in the
      right middle frontal gyrus, right post-central gyrus, right superior and middle
      temporal gyrus and right cerebellum. The combined cerebral metabolic effects of
      galantamine and citalopram suggest, consistent with preclinical data, a
      synergistic interaction of cholinergic and serotonergic systems.

PMID- 19153153
TI  - Cerebellar ataxia with elevated cerebrospinal free sialic acid (CAFSA).
AB  - In order to identify new metabolic abnormalities in patients with complex
      neurodegenerative disorders of unknown aetiology, we performed high resolution in
      vitro proton nuclear magnetic resonance spectroscopy on patient cerebrospinal
      fluid (CSF) samples. We identified five adult patients, including two sisters,
      with significantly elevated free sialic acid in the CSF compared to both the
      cohort of patients with diseases of unknown aetiology (n = 144; P < 0.001) and a
      control group of patients with well-defined diseases (n = 91; P < 0.001). All
      five patients displayed cerebellar ataxia, with peripheral neuropathy and
      cognitive decline or noteworthy behavioural changes. Cerebral MRI showed mild to
      moderate cerebellar atrophy (5/5) as well as white matter abnormalities in the
      cerebellum including the peridentate region (4/5), and at the periventricular
      level (3/5). Two-dimensional gel analyses revealed significant hyposialylation of
      transferrin in CSF of all patients compared to age-matched controls (P < 0.001)-
      a finding not present in the CSF of patients with Salla disease, the most common
      free sialic acid storage disorder. Free sialic acid content was normal in
      patients' urine and cultured fibroblasts as were plasma glycosylation patterns of
      transferrin. Analysis of the ganglioside profile in peripheral nerve biopsies of
      two out of five patients was also normal. Sequencing of four candidate genes in
      the free sialic acid biosynthetic pathway did not reveal any mutation. We
      therefore identified a new free sialic acid syndrome in which cerebellar ataxia
      is the leading symptom. The term CAFSA is suggested (cerebellar ataxia with free
      sialic acid).

PMID- 19153154
TI  - Differential endogenous pain modulation in complex-regional pain syndrome.
AB  - Endogenous pain modulation may provide facilitation or inhibition of nociceptive
      input by three main mechanisms. Firstly, modification of synaptic strength in the
      spinal dorsal horn may increase or decrease transmission of nociceptive signals
      to the brain. Secondly, local dorsal horn interneurons provide both feed-forward
      and feed-back modulation to spinothalamic and spinobulbar projection neurons.
      Thirdly, descending systems originating in the brainstem exert top-down
      modulation of nociceptive input at the spinal level. Not much is known on the
      activity of these systems in complex regional pain syndrome (CRPS). CRPS is a
      chronic pain condition characterized by burning pain and abnormalities in the
      sensory, motor and autonomous nervous system. In the present study, we tested
      changes in endogenous pain modulation in 27 CRPS patients compared with age
      matched healthy controls. We applied repetitive noxious electrical stimuli
      (stimulation frequency 1 Hz) at the dorsal aspect of affected and unaffected
      hands in patients and to corresponding hands in controls. As known from previous
      studies this protocol simultaneously activates inhibitory and facilitatory pain
      modulating systems. This results in adaptation to the repetitive noxious
      stimulus, and simultaneously and at the same site, in development of an area of
      pinprick hyperalgesia. We measured (i) pain adaptation during the course of
      stimulation and (ii) the provoked area of pinprick hyperalgesia. These parameters
      were used as activity measures of pain inhibitory and pain facilitatory systems.
      As both measures result from gross inhibitory and gross facilitatory activity in
      pain modulatory systems, pain adaptation reflects net pain inhibition and area of
      pinprick hyperalgesia net pain facilitation. We found (i) decreased adaptation to
      painful electrical stimuli on both affected and unaffected hands of CRPS patients
      compared to healthy controls and (ii) increased areas of hyperalgesia on affected
      hands of CRPS patients compared to unaffected hands of CRPS patients and healthy
      controls. These findings imply a shift from inhibition towards facilitation of
      nociceptive input in CRPS patients, based on differential activation of
      subcomponents of the endogenous pain modulatory system. The differences were not
      correlated with duration of the disease, pain intensity, autonomic or motor
      function scores, presence or degree of evoked pain. However, significant
      correlation was found with the extent of adaptation and hyperalgesia on the
      unaffected hand. Thus, we hypothesize that differential activity in endogenous
      pain modulating systems may be not only a result of CRPS, but a potential risk
      factor for its development.

PMID- 19153156
TI  - BARREN INFLORESCENCE2 interaction with ZmPIN1a suggests a role in auxin transport
      during maize inflorescence development.
AB  - Polar auxin transport, mediated by the PIN-FORMED (PIN) class of auxin efflux
      carriers, controls organ initiation in plants. In maize, BARREN INFLORESCENCE2
      (BIF2) encodes a serine/threonine protein kinase co-orthologous to PINOID (PID),
      which regulates the subcellular localization of AtPIN1 in Arabidopsis. We show
      that BIF2 phosphorylates ZmPIN1a, a maize homolog of AtPIN1, in vitro and
      regulates ZmPIN1a subcellular localization in vivo, similar to the role of PID in
      Arabidopsis. In addition, bif2 mutant inflorescences have lower auxin levels
      later in development. We propose that BIF2 regulates auxin transport through
      direct regulation of ZmPIN1a during maize inflorescence development.

PMID- 19153155
TI  - Social conceptual impairments in frontotemporal lobar degeneration with right
      anterior temporal hypometabolism.
AB  - Inappropriate social behaviours are early and distinctive symptoms of the
      temporal and frontal variants of frontotemporal lobar degeneration (FTLD).
      Knowledge of social behaviour is essential for appropriate social conduct. It is
      unknown, however, in what way this knowledge is degraded in FTLD. In a recent
      functional MRI study, we have identified a right-lateralized superior anterior
      temporal lobe (aTL) region showing selective activation for 'social concepts'
      (i.e. concepts describing social behaviour: e.g. 'polite', 'stingy') as compared
      with concepts describing less socially relevant animal behaviour ('animal
      function concepts': e.g. 'trainable', 'nutritious'). In a further fMRI study,
      superior aTL activation was independent of the context of actions and feelings
      associated with these social concepts. Here, we investigated whether the right
      superior sector of the aTL is necessary for context-independent knowledge of
      social concepts. We assessed neuronal glucose uptake using 18-fluoro-deoxy
      glucose-positron emission tomography (FDG-PET) and a novel semantic
      discrimination task which probed knowledge of social and animal function concepts
      in patients with FTLD (n = 29) and corticobasal syndrome (n = 18). FTLD and
      corticobasal syndrome groups performed equally poorly on animal function concepts
      but FTLD patients showed more pronounced impairments on social concepts than
      corticobasal syndrome patients. FTLD patients with right superior aTL
      hypometabolism, as determined on individual ROI analyses, were significantly more
      impaired on social concepts than on animal function concepts. FTLD patients with
      selective impairments for social concepts, as determined on individual
      neuropsychological profiles, showed higher levels of inappropriate social
      behaviours ('disinhibition') and demonstrated more pronounced hypometabolism in
      the right superior aTL, the left temporal pole and the right lateral
      orbitofrontal and dorsomedial prefrontal cortex as compared with FTLD patients
      showing selective impairments of animal function concepts. Combining both FTLD
      subgroup analyses, based on anatomical and neuropsychological criteria, by using
      inclusive masks, revealed the right superior aTL as associated with selective
      impairments of social concepts in both analyses. These results corroborate the
      hypothesis that the right aTL is necessary for representing conceptual social
      knowledge. Further, we provide first evidence for the potential importance of
      conceptual social knowledge impairments as contributing to behavioural symptoms
      of FTLD.

PMID- 19153157
TI  - Molecular characterization of a putative sucrose:fructan 6-fructosyltransferase
      (6-SFT) of the cold-resistant Patagonian grass Bromus pictus associated with
      fructan accumulation under low temperatures.
AB  - Fructans are fructose polymers synthesized from sucrose in the plant vacuole.
      They represent short- and long-term carbohydrate reserves and have been
      associated with abiotic stress tolerance in graminean species. We report the
      isolation and characterization of a putative sucrose:fructan 6
      fructosyltransferase (6-SFT) gene from a Patagonian grass species, Bromus pictus,
      tolerant to drought and cold temperatures. Structural and functional analyses of
      this gene were performed by Southern and Northern blot. Sugar content, quality
      and fructosyltransferase activity were studied using HPAEC-PAD (high-pH anion
      exchange chromatography with pulsed amperometric detection), enzymatic and
      colorimetric assays. The putative 6-SFT gene had all the conserved motifs of
      fructosyl-transferase and showed 90% identity at the amino acid level with other
      6-SFTs from winter cereals. Expression studies, and determination of sugar
      content and fructosyl-transferase activity were performed on five sections of the
      leaf. Bp6-SFT was expressed predominantly in leaf bases, where
      fructosyltransferase activity and fructan content are higher. Bp6-SFT expression
      and accumulation of fructans showed different patterns in the evaluated leaf
      sections during a 7 d time course experiment under chilling treatment. The
      transcriptional pattern suggests that the B. pictus 6-SFT gene is highly
      expressed in basal leaf sections even under control temperate conditions, in
      contrast to previous reports in other graminean species. Low temperatures caused
      an increase in Bp6-SFT expression and fructan accumulation in leaf bases. This is
      the first study of the isolation and molecular characterization of a
      fructosyltransferase in a native species from the Patagonian region. Expression
      in heterologous systems will confirm the functionality, allowing future
      developments in generation of functional markers for assisted breeding or
      biotechnological applications.

PMID- 19153158
TI  - Defining the role of GABA in cortical development.
AB  - Of the many signals in the developing nervous system, GABA (gamma-aminobutyric
      acid) has been shown to be one of the earliest neurotransmitters present. Unlike
      in the adult, where this transmitter acts synaptically to inhibit neurons, during
      development, GABA can depolarize progenitor cells and their progeny due to their
      high intracellular chloride concentration. This early form of GABA signalling may
      provide the main excitatory drive for the immature cortical network and play a
      central role in regulating cortical development. Many features of GABA signalling
      are conserved in different species and are recapitulated during neurogenesis in
      the adult brain, demonstrating the importance of this versatile molecule in
      driving cortical formation. Here, we present recent evidence supporting the
      multiple functions of GABA during embryonic development and adult neurogenesis,
      from regulating progenitor proliferation to influencing the migration and
      maturation of newborn neurons.

PMID- 19153159
TI  - Voltage-dependent and -independent titration of specific residues accounts for
      complex gating of a ClC chloride channel by extracellular protons.
AB  - The ClC transport protein family comprises both Cl(-) ion channel and H(+)/Cl(-)
      and H(+)/NO(3)(-) exchanger members. Structural studies on a bacterial ClC
      transporter reveal a pore obstructed at its external opening by a glutamate side
      chain which acts as a gate for Cl(-) passage and in addition serves as a staging
      post for H(+) exchange. This same conserved glutamate acts as a gate to regulate
      Cl(-) flow in ClC channels. The activity of ClC-2, a genuine Cl(-) channel, has a
      biphasic response to extracellular pH with activation by moderate acidification
      followed by abrupt channel closure at pH values lower than approximately 7. We
      have now investigated the molecular basis of this complex gating behaviour.
      First, we identify a sensor that couples extracellular acidification to complete
      closure of the channel. This is extracellularly-facing histidine 532 at the N
      terminus of transmembrane helix Q whose neutralisation leads to channel closure
      in a cooperative manner. We go on to show that acidification-dependent activation
      of ClC-2 is voltage dependent and probably mediated by protonation of pore gate
      glutamate 207. Intracellular Cl(-) acts as a voltage-independent modulator, as
      though regulating the pK(a) of the protonatable residue. Our results suggest that
      voltage dependence of ClC-2 is given by hyperpolarisation-dependent penetration
      of protons from the extracellular side to neutralise the glutamate gate deep
      within the channel, which allows Cl(-) efflux. This is reminiscent of a partial
      exchanger cycle, suggesting that the ClC-2 channel evolved from its transporter
      counterparts.

PMID- 19153160
TI  - The spatial pattern of exocytosis and post-exocytic mobility of synaptopHluorin
      in mouse motor nerve terminals.
AB  - We monitored the spatial distribution of exo- and endocytosis at 37 degrees C in
      mouse motor nerve terminals expressing synaptopHluorin (spH), confirming and
      extending earlier work at room temperature, which had revealed fluorescent 'hot
      spots' appearing in repeatable locations during tetanic stimulation. We also
      tested whether hot spots appeared during mild stimulation. Averaged responses
      from single shocks showed a clear fluorescence jump, but revealed no sign of hot
      spots; instead, fluorescence rose uniformly across the terminal. Only after 5-25
      stimuli given at high frequency did hot spots appear, suggesting a novel
      initiation mechanism. Experiments showed that about half of the surface spH
      molecules were mobile, and that spH movement occurred out of hot spots,
      demonstrating their origin as exocytic sources, not endocytic sinks. Taken
      together, our results suggest that synaptic vesicles exocytose equally throughout
      the terminal with mild stimulation, but preferentially exocytose at specific,
      repeatable locations during tetanic stimulation.

PMID- 19153161
TI  - The effects of membrane potential, SR Ca2+ content and RyR responsiveness on
      systolic Ca2+ alternans in rat ventricular myocytes.
AB  - Previous work has shown that small depolarizing pulses produce a beat to beat
      alternation in the amplitude of the systolic Ca(2+) transient in ventricular
      myocytes. The aim of the present work was to investigate the role of changes of
      SR Ca(2+) content and L-type Ca(2+) current in this alternans. As the amplitude
      of the depolarizing pulse was increased from 10 to 30 mV the magnitude of
      alternans decreased. Confocal linescan studies showed that this was accompanied
      by an increase in the number of sites from which Ca(2+) waves propagated. A
      sudden decrease in the depolarisation amplitude resulted in three classes of
      behaviour: (1) a gradual decrease in Ca(2+) transient amplitude before alternans
      developed accompanied by a loss of SR Ca(2+), (2) a gradual increase in Ca(2+)
      transient amplitude before alternans accompanied by a gain of SR Ca(2+), and (3)
      immediate development of alternans with no change of SR content. We conclude that
      alternans develops if the combination of decreased opening of L-type channels and
      change of SR Ca(2+) content results in spatially fragmented release from the SR
      as long as there is sufficient Ca(2+) in the SR to sustain wave propagation.
      Potentiation of the opening of the ryanodine receptor (RyR) by low concentrations
      of caffeine (100 microm) abolished alternans for a few pulses but the alternans
      then redeveloped once SR Ca(2+) content fell to the new threshold for wave
      propagation. Finally we show evidence that inhibiting L-type Ca(2+) current with
      200 mum Cd(2+) produces alternans by means of a similar fragmentation of the
      Ca(2+) release profile and propagation of mini-waves of Ca(2+) release.

PMID- 19153162
TI  - Excitation-contraction coupling gain in ventricular myocytes: insights from a
      parsimonious model.
AB  - We present a minimal mathematical model of Ca(2+) spark triggering under voltage
      clamp conditions in ventricular myocytes. The model predicts changes in
      excitation-contraction coupling 'gain' that result from diverse experimental
      interventions. We compare model results to several sets of data, and, in so
      doing, place apparent constraints on physiologically relevant model parameters.
      Specifically, the analysis suggests that many L-type Ca(2+) channel openings can
      potentially trigger each Ca(2+) spark, but the probability that an individual
      opening will trigger a spark is low. This procedure helps to reconcile
      contradictory results obtained in recent studies; moreover, this new model should
      be a useful tool for understanding changes in gain that occur physiologically and
      in disease.

PMID- 19153163
TI  - Consequences of axon guidance defects on the development of retinotopic receptive
      fields in the mouse colliculus.
AB  - Gradients of molecular factors pattern the developing retina and superior
      colliculus (SC) and guide retinal ganglion cell (RGC) axons to their appropriate
      central target perinatally. During and subsequent to this period, spontaneous
      waves of action potentials sweep across the retina, providing an instructive
      topographic signal based on the correlations of firing patterns of neighbouring
      RGCs. How these activity-independent and activity-dependent factors interact
      during retinotopic map formation remains unclear. A typical phenotype of mutant
      mice lacking genes for one or more RGC axon guidance molecules is the presence of
      topographically inappropriate projections or 'ectopic spots'. Here, we examine
      mice that lack functional bone morphogenetic protein receptors (BMPRs) in the
      retina. Retinal BMP controls the graded expression of RGC axon guidance
      molecules, resulting in some dorsal RGCs projecting ectopically to locations in
      the SC that normally receive input from ventral retina. We examine the
      consequences of this anatomical phenotype in vivo by studying the receptive field
      (RF) properties of neurons in the superficial SC. We observe a mixture of
      physiological phenotypes in BMPR mutant mice; notably we find some neurons with
      ectopic RFs displaced in elevation, corresponding to the observed anatomical
      defect. However, in a result not necessarily congruent with the presence of focal
      ectopic projections, some neurons have split, enlarged and patchy/distorted RFs.
      These results are consistent with the effects of spontaneous retinal waves acting
      upon a disrupted molecular template, and they place significant limits on the
      form of an activity-dependent learning rule for the development of
      retinocollicular projections.

PMID- 19153164
TI  - Medications as risk factors of Stevens-Johnson syndrome and toxic epidermal
      necrolysis in children: a pooled analysis.
AB  - OBJECTIVE: The aim of this study was to determine the relation of medications to
      the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in children
      <15 years of age. METHODS: We conducted a pooled analysis by using data from 2
      multicenter international case-control studies: the severe cutaneous adverse
      reaction (SCAR) study and the multinational severe cutaneous adverse reaction
      (EuroSCAR) study conducted in France, Germany, Italy, Portugal, the Netherlands,
      Austria, and Israel. We selected case subjects aged <15 years, hospitalized for
      Stevens-Johnson syndrome, Stevens-Johnson syndrome/toxic epidermal necrolysis
      overlap, or toxic epidermal necrolysis, and age-, gender-, and country-matched
      hospital controls. Pooled crude odds ratios were estimated and adjusted for
      confounding by multivariate methods when numbers permitted. RESULTS: Our study
      included 80 cases and 216 matched controls. Antiinfective sulfonamides,
      phenobarbital, carbamazepine, and lamotrigine were strongly associated with the
      risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. Significant
      associations were highlighted in univariate analysis for valproic acid and
      nonsteroidal antiinflammatory drugs as a group and for acetaminophen
      (paracetamol) in multivariate analysis. CONCLUSIONS: We confirmed 4 previously
      highly suspected drug risk factors for Stevens-Johnson syndrome/toxic epidermal
      necrolysis in children: antiinfective sulfonamides, phenobarbital, carbamazepine,
      and lamotrigine. Among more unexpected risk factors, we suspect that
      acetaminophen (paracetamol) use increases the risk of Stevens-Johnson syndrome or
      toxic epidermal necrolysis.

PMID- 19153165
TI  - Amplitude-integrated electroencephalography in the NICU: frequent artifacts in
      premature infants may limit its utility as a monitoring device.
AB  - BACKGROUND: Amplitude-integrated electroencephalography has become an important
      tool for assessing cortical status noninvasively. Newer units have the additional
      feature of visualizing the raw electroencephalogram, which has resulted in the
      identification of frequent artifacts. OBJECTIVE: To highlight the problem of
      artifacts and to introduce caution when using the amplitude-integrated
      electroencephalography technique to assess cortical function in the premature
      population. METHODS: Ten premature infants were evaluated. Compressed amplitude
      integrated electroencephalography recordings were made by using a pair of
      standard electroencephalogram electrodes attached to the scalp frontotemporal
      areas. Impedance was maintained at <10 kOmega. Continuous amplitude-integrated
      electroencephalography recordings were performed for at least 60 minutes on
      several occasions in the first month. Artifacts were identified as follows: large
      amplitude difference between the wave peaks and troughs, a jagged appearance to
      wave peaks and troughs, and large deflections of the overall tracing in either a
      positive or negative direction from baseline. RESULTS: Forty-eight amplitude
      integrated electroencephalography recordings were reviewed. Of 1683 total
      segments analyzed, 529 (31.4%) were categorized as normal brain waves, 1013
      (60.2%) as artifacts, and 142 (8.4%) as indeterminate. Generally, when the
      amplitude-integrated electroencephalography tracing is of modest amplitude,
      normal brain waves predominated, whereas with upward spikes in amplitude the
      accompanying raw electroencephalogram was classified as artifact. CONCLUSIONS:
      Artifacts contribute substantially to the amplitude-integrated
      electroencephalography tracing, rendering it problematic as an assessment tool in
      premature infants. Artifacts may be influenced by muscle activity, electrode
      positioning, and application techniques. Caution is recommended when using
      amplitude-integrated electroencephalography as an assessment tool in this
      population.

PMID- 19153166
TI  - Modelling the evolution of multi-gene families.
AB  - A number of biological processes can lead to genes being copied within the genome
      of some given species. Duplicate genes of this form are called paralogs and such
      genes share a high degree sequence similarity as well as often having closely
      related functions. Some genes have become widely duplicated to form multigene
      families in which the copies are distributed both within the genomes of
      individual species and across different species. Statistical modelling of gene
      duplication and the evolution of multi-gene families currently lags behind well
      established models of DNA sequence evolution despite an increasing volume of
      available data, but the analysis of multi-gene families is important as part of a
      wider effort to understand evolution at the genomic level. This article reviews
      existing approaches to modelling multi-gene families and presents various
      challenges and possibilities for this exciting area of research.

PMID- 19153167
TI  - Selection of covariance patterns for longitudinal data in semi-parametric models.
AB  - The use of patterned covariance structures in the parametric analysis of
      longitudinal data is both elegant and efficient. However, this strategy has not
      been well studied for semi-parametric models for analysing such data. We propose
      to estimate the covariance matrix in the semi-parametric model by rearranging the
      non-parametric component as a profiled linear function of the data and using a
      local smoothing technique. This results in a parametric regression formulation
      that enables us to construct likelihood functions and use various information
      criteria to select the best fitting covariance matrix. We apply our method to
      reanalyse data from a two-armed clinical trial for Scleroderma patients and show
      our method is more efficient for estimating the parametric components in the semi
      parametric model.

PMID- 19153168
TI  - Probabilistic models and machine learning in structural bioinformatics.
AB  - Structural bioinformatics is concerned with the molecular structure of
      biomacromolecules on a genomic scale, using computational methods. Classic
      problems in structural bioinformatics include the prediction of protein and RNA
      structure from sequence, the design of artificial proteins or enzymes, and the
      automated analysis and comparison of biomacromolecules in atomic detail. The
      determination of macromolecular structure from experimental data (for example
      coming from nuclear magnetic resonance, X-ray crystallography or small angle X
      ray scattering) has close ties with the field of structural bioinformatics.
      Recently, probabilistic models and machine learning methods based on Bayesian
      principles are providing efficient and rigorous solutions to challenging problems
      that were long regarded as intractable. In this review, I will highlight some
      important recent developments in the prediction, analysis and experimental
      determination of macromolecular structure that are based on such methods. These
      developments include generative models of protein structure, the estimation of
      the parameters of energy functions that are used in structure prediction, the
      superposition of macromolecules and structure determination methods that are
      based on inference. Although this review is not exhaustive, I believe the
      selected topics give a good impression of the exciting new, probabilistic road
      the field of structural bioinformatics is taking.

PMID- 19153169
TI  - Considerations for the processing and analysis of GoldenGate-based two-colour
      Illumina platforms.
AB  - Illumina's GoldenGate technology is a two-channel microarray platform that allows
      for the simultaneous interrogation of about 1,500 locations in the genome.
      GoldenGate has proved a flexible platform not only in the choice of those 1,500
      locations, but also in the choice of the property being measured at them. It
      retains the desirable properties of Illumina's BeadArrays in that the probes (in
      this case 'beads') are randomly arranged across the microarray, there are
      multiple instances of each probe and many samples can be processed
      simultaneously. As for other Illumina technologies, however, these properties are
      not exploited as they might be. Here we review the various common adaptations of
      the GoldenGate platform, review the analysis methods that are associated with
      each adaptation and then, with the aid of a number of example data sets we
      illustrate some of the improvements that can be made over the default analysis.

PMID- 19153170
TI  - Can a mini-bypass circuit improve perfusion in cardiac surgery compared to
      conventional cardiopulmonary bypass?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether the 'mini-bypass technique' can give
      a reduction in complications after cardiac surgery compared to the conventional
      cardiopulmonary bypass circuit. Altogether 144 papers were found using the
      reported search, of which 14 represented the best evidence to answer the clinical
      question. The authors, journal, date and country of publication, patient group
      studied, study type, relevant outcomes and results of these papers are tabulated.
      We conclude that 10 out of these 14 studies show reduced hemodilution, 7 show
      reduced red blood cell transfusion, 2 show reduced fresh frozen plasma use (one
      showing increased use), and 2 show reduced platelet use. Three studies show
      reduced postoperative blood loss, but one shows increased blood loss. Three
      studies show better renal function. Four studies show a better cardiac index and
      2 show shorter intensive care unit stay. One study found an increased minute
      volume and reduced oxygenation for one hour post-mini-bypass. Six studies find
      significantly reduced inflammatory markers, and 5 measure superior myocardial
      protection. There are several anecdotal references to a 'learning curve' with
      this technique but no significant morbidity with complications arising from this
      were found. Mini-bypass seems to be a promising technique with many documented
      benefits in studies reporting as many as 1000 patients undergoing this technique.

PMID- 19153171
TI  - The contribution of cerebrospinal fluid oligoclonal bands to the early diagnosis
      of multiple sclerosis.
AB  - BACKGROUND: McDonald Criteria (MDC) have been validated in selected patients at
      high risk for multiple sclerosis (MS). However, possible overdiagnosis of MS can
      represent critical issues in less controlled clinical settings. OBJECTIVE: To
      assess the contribution of oligoclonal bands (OB) to MS diagnosis in current
      clinical practice. METHODS: We included all the patients admitted to our
      Department since 2001 who had undergone diagnostic workup for a possible MS
      diagnosis, followed up for at least 1 year. We assessed the accuracy of MDC, OB,
      and two MDC definitions of dissemination in space (DIS-MRI: fulfillment of MRI
      criteria, DIS-OB: two MRI lesions+OB). RESULTS: We included 118 patients (median
      follow-up 4.0 years). Twenty-eight cases received an alternative diagnosis,
      whereas none of these presented OB, 43% fulfilled the DIS-MRI criteria. OB were
      present in 70% of the remaining 90 patients. By the end of the follow-up, 56% of
      the diagnoses had converted to clinically definite MS and OB showed higher
      accuracy than DIS-MRI fulfillment (70% vs 58%). Moreover, after 1 year and at the
      end of the follow-up, DIS-OB yielded a higher Specificity level in comparison
      with DIS-MRI. CONCLUSION: OB can improve overall diagnostic Accuracy by
      increasing Specificity and negative predictive value.

PMID- 19153172
TI  - Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis.
AB  - BACKGROUND: Cell and animal experiments have shown that beta-site APP-cleaving
      enzyme 1 (BACE1) may be involved in myelination. OBJECTIVE: Here, we assess the
      association of cerebrospinal fluid (CSF) BACE1 activity with multiple sclerosis
      (MS). METHODS: BACE1 activity and levels of secreted amyloid precursor protein
      (APP) and amyloid-beta (Abeta) isoforms were analyzed in CSF from 100 patients
      with MS and 114 neurologically healthy controls. Patients with systemic lupus
      erythematosus (SLE), 26 with and 41 without cerebral engagement, were also
      included to enable comparisons with regards to another autoimmune disease. A
      subset of patients with MS and controls underwent a second lumbar puncture after
      10 years. RESULTS: MS patients had lower CSF BACE1 activity than controls (P =
      0.03) and patients with cerebral SLE (P < 0.001). Patients with cerebral SLE had
      higher BACE1 activity than any other group (P < 0.05 for all comparisons). BACE1
      activity correlated with the different amyloid markers in all study groups. BACE1
      activity decreased over 10 years in the MS group (P = 0.039) and correlated
      weakly with clinical disease severity scores in an inverse manner. CONCLUSIONS:
      These results suggest an involvement of BACE1 in the MS disease process.

PMID- 19153173
TI  - Matrix metalloproteinase-9 and matrix metalloproteinase-2 as biomarkers of
      various courses in multiple sclerosis.
AB  - BACKGROUND: Matrix metalloproteinases are notable contributors to
      neuroinflammation and blood-brain barrier disruption in multiple sclerosis (MS).
      OBJECTIVE: The goal of this study was to determine the serum levels of matrix
      metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), and their tissue
      inhibitors (TIMP-1) and (TIMP-2), and to investigate their possible relations to
      type, disability, and severity of MS. MATERIALS AND METHODS: Eighty-seven
      patients with definite MS according to the McDonald criteria and 50 healthy
      controls were enrolled in the study. Their clinical status was evaluated with the
      Expanded Disability Status Scale. Serum levels were analyzed by enzyme-linked
      immunoassay. RESULTS: A significant elevation in MMP-9 serum levels and in the
      MMP-9/TIMP-1 ratio was found in the whole MS group (P<0.001), in the relapsing
      remitting MS (RRMS) (P<0.001), and secondary-progressive MS (SPMS) (P<0.001)
      groups when compared with the controls. A significant elevation in MMP-2 serum
      levels and in the MMP-2/TIMP-2 ratio was observed in the primary progressive
      (P<0.001) and the SPMS (P<0.002) groups when compared with the RRMS group, and
      this increase was also associated with the disability (P<0.001) and severity
      (P<0.05) of the disease. CONCLUSION: We confirmed that metalloproteinases are
      useful biological markers in MS, providing information about the clinical type,
      disability, and severity of the disease.

PMID- 19153174
TI  - Effects of infectious mononucleosis and HLA-DRB1*15 in multiple sclerosis.
AB  - BACKGROUND: Both human leukocyte antigen (HLA)-DRB1*15 and Epstein-Barr virus
      infection presenting as infectious mononucleosis (IM) are recognized as risk
      factors for multiple sclerosis (MS). However, their combined effect and possible
      interaction on MS risk is not known. OBJECTIVE: To assess the association between
      HLA-DRB1*15 and risk of MS in persons with and without IM. METHODS: We compared
      the prevalence of DRB1*15 in MS patients with (n = 76) and without (n = 1,836) IM
      with the corresponding distributions in blood donors with (n = 62) and without (n
      = 484) IM histories. This allowed us to estimate the relative risk of MS
      associated with DRB1*15 in the presence and absence, respectively, of previous
      IM. We then estimated the interaction between DRB1*15 and IM as the ratio of the
      two individual odds ratios. RESULTS: In IM-naive individuals, DRB1*15 carried a
      2.4-fold (95% confidence interval [CI], 2.0-3.0) increased MS risk. In contrast,
      among persons with IM history, DRB1*15 was associated with a 7.0-fold (95% CI,
      3.3-15.4) increased MS risk. Thus, the MS risk conferred by HLA-DRB1*15 was 2.9
      (95% CI, 1.3-6.5)-fold stronger in the presence than in the absence of IM.
      Combined with previous results, this result indicates that DRB1*15-positive
      persons with a history of IM may be at a 10.0-fold (95% CI, 6.0-17.9) increased
      risk of MS compared with persons who are DRB1*15 and IM-naive. CONCLUSION:
      DRB1*15 and IM may act in synergy causing MS.

PMID- 19153175
TI  - Motor evoked potentials in clinically isolated syndrome suggestive of multiple
      sclerosis.
AB  - The aim of the present study was to determine the sensitivity and the profile of
      motor evoked potentials (MEP) in patients with clinically isolated syndrome (CIS)
      suggestive of multiple sclerosis (MS). We measured the central motor conduction
      time (CMCT), amplitude ratio (AR), and surface ratio (SR) in tibialis anterior
      and first dorsal interosseous muscles in 22 patients with CIS. In 12 patients,
      the triple stimulation technique (TST) was also performed. AR was abnormal in 50%
      of patients, CMCT in 18% of patients, and TST in 25% of patients. AR had the
      highest sub-clinical sensitivity and the best positive predictive value. In the
      absence of clinical pyramidal signs, an early AR decrease seems to result from
      demyelination inducing excessive temporal dispersion of the MEP, while in
      territories with clinical pyramidal signs, it seems to result from conduction
      failure, which suggests that clinical pyramidal signs may be attributable to
      conduction failure. This study demonstrates that MEP, especially the AR, is
      sensitive to motor pathway dysfunction right from the early stages of MS.

PMID- 19153176
TI  - The burden of mental comorbidity in multiple sclerosis: frequent, underdiagnosed,
      and undertreated.
AB  - BACKGROUND: Mental comorbidity is common in multiple sclerosis (MS), but some
      studies suggest that mental comorbidity may be underrecognized and undertreated.
      OBJECTIVE: Using the North American Research Committee on MS Registry, we
      assessed the frequency of mental comorbidities in MS and sociodemographic
      characteristics associated with diagnosis and treatment of depression. METHODS:
      We queried participants regarding depression, anxiety, bipolar disorder, and
      schizophrenia. Depressive symptoms were assessed using the Center for
      Epidemiologic Studies Depression Scale (CESD); a score>or=21 indicated probable
      major depression. RESULTS: Mental comorbidity affected 4264 (48%) responders;
      depression most frequently (4012, 46%). Among participants not reporting mental
      comorbidity, 751 (16.2%) had CESD scores>or=21 suggesting undiagnosed depression.
      Lower socioeconomic status was associated with increased odds of depression
      (Income $15,000-30,000 vs >$100,000 OR 1.34; 1.11-1.62), undiagnosed depression
      (Income $15,000-30,000 vs >$100,000 OR 1.52; 1.08-2.13), and untreated depression
      (<high school vs postgraduate degree OR 3.13; 1.65-5.99). CONCLUSIONS: Mental
      comorbidity remains underdiagnosed and undertreated in MS. Patients of lower
      socioeconomic status bear a disproportionate share of the burden of depression.

PMID- 19153177
TI  - Prognostic utility of 64-slice computed tomography in patients with suspected but
      no documented coronary artery disease.
AB  - AIMS: Although multislice computed tomography (MSCT) detects obstructive coronary
      artery disease (CAD) with high diagnostic accuracy, there is a paucity of long
      term prognostic data. We sought to assess the incremental prognostic value of 64
      slice CT in patients with suspected but no documented CAD. METHODS AND RESULTS:
      Coronary MSCT was performed on 227 individuals (61% men, mean age 54 +/- 12
      years, 63% with intermediate pre-test probability) without documented CAD,
      referred for coronary evaluation. Coronary artery disease by MSCT was categorized
      as follows: none or mild CAD (<50%, n = 172), > or =50% in one vessel (n = 23),
      two vessels [or in the proximal left anterior descending (LAD), n = 12], and
      three vessels (or in two vessels including the proximal LAD or left main, n =
      20). Baseline risk factors, length of follow-up, and major adverse cardiac events
      (MACE), including cardiac death, myocardial infarction (MI), and coronary
      revascularization were recorded. Over a mean follow-up of 2.3 +/- 0.8 years,
      there were 18 MACE [including four hard events (one cardiac death and three
      MIs)]. Also, patients with one or more vessel obstructive CAD had increased hard
      events compared with those with less than one-vessel disease (log-rank statistic
      P-value 0.01). One or more vessel obstructive CAD was a significant predictor of
      MACE on univariable and multivariable Cox proportional survival analysis [hazard
      ratios 29.1 (6.7-126.6) and 9.82 (3.58-27.01), respectively, both P < 0.0001]. In
      172 patients, with no or mild CAD, there was 99% freedom from MACE during follow
      up. CONCLUSION: Multislice computed tomography-classified extent of CAD provides
      incremental prognostic information in patients with suspected but no documented
      CAD.

PMID- 19153178
TI  - Cystatin C and cardiovascular mortality in patients with coronary artery disease
      and normal or mildly reduced kidney function: results from the AtheroGene study.
AB  - AIMS: Chronic kidney disease is associated with increased risk of cardiovascular
      disease. Cystatin C is a promising marker to reliably mirror renal function. The
      role of cystatin C in patients with coronary artery disease (CAD) and normal or
      mildly reduced kidney function is the subject of current investigation. METHODS
      AND RESULTS: In 2162 patients, over the whole spectrum of CAD, baseline cystatin
      C concentrations were measured. Patients with an estimated glomerular filtration
      rate of < or =60 mL/min per 1.73 m(2) (n = 295) were excluded. In patients with
      complete follow-up information (n = 1827), 66 cardiovascular deaths were
      registered during a median follow-up of 3.65 years. Logarithmically transformed,
      standardized cystatin C was associated with cardiovascular death [hazard ratio:
      1.94, 95% confidence interval (CI): 1.59-2.37, P < 0.001]. A potential threshold
      effect was observed; patients in the upper quartile had a 3.87-fold (95% CI: 2.33
      6.42; P < 0.001) risk of mortality compared with the pooled lower quartiles. This
      risk association remained robust after adjustment for potential confounders
      including classical risk factors and N-terminal pro B-type natriuretic peptide.
      Serum creatinine was not associated with the outcome in this group of patients
      with normal renal function. CONCLUSION: Results of this prospective study show
      that cystatin C is a potent predictor of cardiovascular mortality beyond
      classical risk factors in patients with CAD and normal or mildly reduced kidney
      function.

PMID- 19153179
TI  - Predictors and time-related impact of distal embolization during primary
      angioplasty.
AB  - AIMS: We sought to identify predictors of distal embolization (DE) occurring
      during primary percutaneous coronary intervention (p-PCI) as well as to assess
      its impact on both myocardial reperfusion and necrosis, according to time-to
      treatment. METHODS AND RESULTS: Clinical and angiographic characteristics were
      prospectively assessed in 400 consecutive patients who underwent p-PCI, in order
      to identify predictors of DE. The impact of DE on Thrombolysis in Myocardial
      Infarction (TIMI) flow, myocardial blush, and troponin I (TnI) was assessed
      according to symptom onset-to-balloon time. DE occurred in 64 (16%) patients and
      did not change with time-to-treatment (P = 0.87). The occlusion pattern of
      infarct-related artery (IRA), treatment of right coronary artery, higher TIMI
      thrombus score, longer lesion, and large IRA diameter were predictors of DE. The
      rate of TIMI 0/1 and myocardial blush 0/1 was higher in patients exhibiting DE
      when time-to-treatment was < or =6 h (P < 0.0001), while TnI was higher in
      patients with DE when time-to-treatment was <3 h. CONCLUSION: DE during p-PCI
      occurs more often in the presence of high thrombus burden lesion. It reduces the
      effectiveness of myocardial reperfusion within 6 h and enhances myocardial damage
      within 3 h after symptom onset. Afterwards, it does not affect myocardial
      reperfusion or the extent of myocardial damage.

PMID- 19153180
TI  - MR vs CT imaging: low rectal cancer tumour delineation for three-dimensional
      conformal radiotherapy.
AB  - Modern three-dimentional radiotherapy is based upon CT. For rectal cancer, this
      relies upon target definition on CT, which is not the optimal imaging modality.
      The major limitation of CT is its low inherent contrast resolution. Targets
      defined by MRI could facilitate smaller, more accurate, tumour volumes than CT.
      Our study reviewed imaging and planning data for 10 patients with locally
      advanced low rectal cancer (defined as < 6 cm from the anal verge on digital
      examination). Tumour volume and location were compared for sagittal pre-treatment
      MRI and planning CT. CT consistently overestimated all tumour radiological
      parameters. Estimates of tumour volume, tumour length and height of proximal
      tumour from the anal verge were larger on planning CT than on MRI (p < 0.05).
      Tumour volumes defined on MRI are smaller, shorter and more distal from the anal
      sphincter than CT-based volumes. For radiotherapy planning, this may result in
      smaller treatment volumes, which could lead to a reduction in dose to organs at
      risk and facilitate dose escalation.

PMID- 19153181
TI  - Evaluation of the potential of hexamethylenetetramine, compared with
      tirapazamine, as a combined agent with {gamma}-irradiation and cisplatin
      treatment in vivo.
AB  - The purpose of this investigation was to compare the effect on intratumour
      quiescent (Q) cells in vivo of hexamethylenetetramine (HMTA) or tirapazamine
      (TPZ) in combination with gamma-irradiation and cisplatin treatment. Squamous
      cell carcinoma (SCC) VII tumour-bearing mice were administered 5-bromo-2'
      deoxyuridine (BrdU) continuously to label all intratumour proliferating (P)
      cells. The mice then received HMTA or TPZ intraperitoneally or continuously with
      or without gamma-irradiation or cisplatin treatment. Other tumour-bearing mice
      received HMTA or TPZ intraperitoneally immediately after gamma-irradiation.
      Immediately after gamma-irradiation or cisplatin treatment following HMTA or TPZ,
      or 24 h after gamma-irradiation followed by HMTA or TPZ, the response of Q cells
      was assessed in terms of the micronucleus frequency using immunofluorescence
      staining for BrdU. The response of all tumour cells (P + Q) was determined from
      the BrdU-non-treated tumours. HMTA was more toxic to the subset of Q cells than
      to the population of tumour cells as a whole, similar to the findings for TPZ.
      The radiosensitising effect of HMTA was similar to that of TPZ in both all cells
      and Q cells. The recovery-inhibiting effect of HMTA was reliable, but not as
      great as that of TPZ. The cisplatin sensitivity-enhancing effect of HMTA was
      similar to or slightly greater than that of TPZ. Continuous administration of
      both HMTA and TPZ resulted in higher radiosensitivity- and cisplatin sensitivity
      enhancing effects than did a single i.p. administration. We concluded that, in
      terms of the total tumour cell killing effect, including killing of Q cells,
      gamma-irradiation and cisplatin treatment combined with continuous HMTA
      administration is a promising strategy given that HMTA is used in clinics.

PMID- 19153182
TI  - Three-dimensional simulation of lung nodules for paediatric multidetector array
      CT.
AB  - The purpose of this study was to develop and validate a technique for three
      dimensional (3D) modelling of small lung nodules on paediatric multidetector
      array computed tomography (MDCT) images. Clinical images were selected from 21
      patients (<18 years old) who underwent MDCT examinations. Sixteen of the patients
      had one or more real lung nodules with diameters between 2.5 and 6 mm. A
      mathematical simulation technique was developed to emulate the 3D characteristics
      of the real nodules. To validate this technique, MDCT images of 34 real nodules
      and 55 simulated nodules were randomised and rated independently by four
      experienced paediatric radiologists on a continuous scale of appearance between 0
      (definitely not real) and 100 (definitely real). Receiver operating
      characteristic (ROC) analysis, t-test, and equivalence test were performed to
      assess the radiologists' ability to distinguish between simulated and real
      nodules. The two types of nodules were also compared in terms of measured shape
      and contrast profile irregularities. The areas under the ROC curves were 0.59,
      0.60, 0.40, and 0.63 for the four observers. Mean score differences between
      simulated and real nodules were -8, -11, 13, and -4 for the four observers with p
      values of 0.17, 0.06, 0.17, and 0.26, respectively. The simulated and real
      nodules were perceptually equivalent and had comparable shape and contrast
      profile irregularities. In conclusion, mathematical simulation is a feasible
      technique for creating realistic small lung nodules on paediatric MDCT images.

PMID- 19153183
TI  - Evaluation of image quality in portal imaging using a combination of a storage
      phosphor plate and diagnostic cassette.
AB  - It is useful to utilise a computed radiography system with a combination of
      storage phosphor plates and therapy cassettes for portal images. However, the
      therapy cassette has some disadvantages. The objective of the present study was
      to determine whether the disadvantages of a diagnostic cassette could be overcome
      to obtain clinically useful portal images. A storage phosphor plate has 0.3 mm of
      lead foil on the distal surface to reduce backscattered radiation. When the plate
      is reversed, the lead foil acts as a front intensifying screen, similar to the
      metal plate of a therapy cassette. We reversed a combination of the diagnostic
      cassette and storage phosphor plate and obtained portal images of the contrast
      detail phantom and the Rando phantom (The Phantom Laboratory, Salem, NY) using
      three types of cassettes: a reversed diagnostic cassette, a therapy cassette and
      a diagnostic cassette. The image quality was subjectively evaluated. The Friedman
      and Wilcoxon tests were applied for statistical analyses. Evaluation of images
      for the contrast-detail phantom revealed that the reversed diagnostic cassette
      was inferior to the therapy cassette and superior to the diagnostic cassette, and
      that the differences were significant (p<0.017). There was no significant
      difference between the reversed diagnostic cassette and therapy cassette (p>0.05)
      for the Rando phantom. Portal images obtained using the reversed diagnostic
      cassette were of sufficiently high quality for clinical use as determined by
      Rando phantom studies.

PMID- 19153184
TI  - Rheumatoid arthritis: a novel radiographic projection for hand assessment.
AB  - Rheumatoid arthritis (RA) is the most common form of inflammatory disease,
      affecting 1-2% of the population. Posteroanterior (PA) and Brewerton projections
      are well established in radiographic practice for scoring and monitoring RA, but
      there is little evidence to demonstrate the diagnostic efficacy of these
      techniques. This work, by varying the positioning of a cadaveric hand,
      investigates whether an alternative radiographic projection could yield greater
      diagnostic information than the traditional techniques. Phase I of the study
      evaluated moving the hand 15 degrees from the anteroposterior position and then
      in 5 degrees increments in four directions: medial rotation, lateral rotation,
      flexion of the wrist and extension of the wrist. Phase II of the study took the
      optimum projections from Phase I and further manipulated these positions in a
      direction at right angles to the original position. Images were scored based on
      joint space visualisation in 29 joints. Results demonstrated that significantly
      higher diagnostic efficacy was evident with 15 degrees lateral rotation of the
      hand or 15 degrees flexion at the wrist compared to the Brewerton projection.
      Either projection is recommended, but on the basis of patient comfort, the latter
      of these novel positions, now known as the UCD projection, was chosen as the
      optimum procedure to replace the Brewerton projection. The value of using
      cadavers for the establishment of optimum radiographic procedures is highlighted.

PMID- 19153185
TI  - Nephrostomy insertion for patients with bilateral ureteric obstruction caused by
      prostate cancer.
AB  - Ureteric obstruction causing renal failure is a serious complication of advanced
      prostate cancer. Percutaneous nephrostomies (PCNs) are used to decompress the
      obstructed kidney(s). This study aims to identify whether bilateral PCN insertion
      confers any advantage over unilateral PCN insertion for patients with bilateral
      ureteric obstruction. In a cohort of 25 patients, 18 underwent bilateral and 7
      underwent unilateral PCN insertion. The mean survival time following PCN was 7.5
      months for all patients. The data suggest that the nadir serum creatinine after
      PCN insertion was similar, independent of whether one or two nephrostomies were
      inserted. There was also little difference in the serum creatinine levels at the
      time of death, suggesting that survival after PCN insertion is based on the
      aggressiveness of the prostate cancer as opposed to the number of nephrostomies
      inserted.

PMID- 19153186
TI  - Non-small-cell lung cancer dimensions: CT-pathological correlation and
      interobserver variation.
AB  - The aim of the study was to identify the most accurate CT window level setting
      for the measurement of non-small-cell lung cancer to optimise CT planning for
      radiotherapy treatment. 27 patients who underwent resection for non-small-cell
      lung cancer in a single institution were studied. The maximal superior-inferior,
      anteroposterior and mediolateral dimensions of the resected tumours were measured
      by a consultant pathologist. Two radiologists made corresponding measurements
      using pre-operative CT scans independently of each other and of the pathologist's
      findings. The measurements were obtained using four different CT window settings.
      The mean pathological size of the superior-inferior tumours, the anteroposterior
      tumours and the mediolateral tumours was 32 mm, 28 mm and 25 mm, respectively. A
      total of 648 CT measurements were taken, of which 321 were within +/-5 mm of the
      pathological size (49.5%). There was significant interobserver variability
      between the two radiologists. There was poor correlation between the pathological
      and radiological measurements of tumour size. Significant interobserver
      variability was noted between the two radiologists and no window setting could be
      identified as being superior in accurately assessing the tumour size.

PMID- 19153187
TI  - Quantification of left-to-right shunting in adult congenital heart disease: phase
      contrast cine MRI compared with invasive oximetry.
AB  - Atrial septum defects (ASDs), ventricular septum defects (VSDs) and patent ductus
      arteriosus (PDA) are the most common adult congenital heart defects. The degree
      of left-to-right shunting as assessed by the ratio of flow in the pulmonary (Qp)
      and systemic circulation (Qs) is crucial in the management of these conditions.
      This study compared phase-contrast cine magnetic resonance imaging (PC-MRI), a
      non-invasive imaging technique, with invasive oximetry for the measurement of
      shunt volumes during cardiac catheterisation in adults with left-to-right
      shunting. Both invasive oximetry and shunt quantification by PC-MRI (1.5 T
      scanner; Sonata, Siemens Medical Solutions) were performed on 21 patients with
      left-to-right shunting (14 ASD, 5 VSD, 2 PDA) and data on Qp/Qs ratios and left
      to-right shunt fraction compared. Mean Qp/Qs ratios assessed by PC-MRI and
      oximetry were 2.10+/-0.76 and 1.96+/-0.77, respectively (p = 0.37). Mean shunt
      fraction was 46.3+/-19.6% when calculated by PC-MRI and 42.3+/-20.1% when
      obtained by oximetry (p = 0.12). There was a strong correlation of Qp/Qs ratios
      and shunt fraction between both methods (r = 0.61, p < 0.01 and r = 0.84, p <
      0.0001, respectively). The two methods had a good agreement according to Bland
      and Altman plots with a small but non-significant overestimation of Qp/Qs-ratios
      and shunt fraction by PC-MRI. On receiver operating characteristic analysis, the
      sensitivity and specificity of PC-MRI to detect an oximetry-derived Qp/Qs ratio
      of > or =1.5:1 were 93% and 100% at a PC-MRI threshold of a Qp/Qs ratio > or
      =1.75:1 (area under curve (AUC) = 0.99). Quantification of left-to-right shunting
      can be performed reliably and accurately by PC-MRI and the data obtained by this
      method correlate closely to those from invasive oximetry.

PMID- 19153188
TI  - Three-dimensional ultrasound measurement of cervical lymph node volume.
AB  - This study evaluated the accuracy of three-dimensional (3-D) ultrasound
      measurement of lymph node volume, and investigated the normal variations of
      cervical nodal volume. The volumes of 12 porcine neck lymph nodes were measured
      with 3-D ultrasound and calculated from two-dimensional (2-D) ultrasound using
      the ellipsoid formula, and compared with the volume measured by the water
      displacement method. 3-D ultrasound of cervical nodes was performed in 100
      subjects, and the volumes of all ultrasound-detectable cervical nodes were
      measured. Results showed that the mean absolute errors of 3-D ultrasound and the
      2-D ellipsoid formula method were 0.042 ml and 0.372 ml, respectively, and the
      mean percentage errors in measurement were 4.4% and 17.8%, respectively. In
      total, 830 nodes were detected in the subjects. Upper cervical nodes (0.48+/-0.47
      ml) were significantly larger than submandibular nodes (0.39+/-0.24 ml) (p<0.05),
      and these two groups of lymph nodes were significantly larger than parotid (0.1+/
      0.06 ml) and posterior triangle (0.1+/-0.11 ml) nodes (p<0.05). There was no
      significant variation of normal cervical node volume with advancing age (p>0.05).
      Men aged 20-29 years had significantly larger cervical nodes than women of the
      same age group (p<0.05), whereas there was no significant gender difference in
      nodal volume in other age groups (p>0.05). 3-D ultrasound measurement of cervical
      nodal volume is feasible. In vitro study showed that 3-D ultrasound had a lower
      mean error than the 2-D ellipsoid formula method in the measurement of cervical
      nodal volume. This study provides baseline information on the normal variations
      of cervical lymph node volume, as measured by 3-D ultrasound.

PMID- 19153189
TI  - Bivariate meta-analysis of sensitivity and specificity of radiographers' plain
      radiograph reporting in clinical practice.
AB  - Studies of diagnostic accuracy often report paired tests for sensitivity and
      specificity that can be pooled separately to produce summary estimates in a meta
      analysis. This was done recently for a systematic review of radiographers'
      reporting accuracy of plain radiographs. The problem with pooling sensitivities
      and specificities separately is that it does not acknowledge any possible
      (negative) correlation between these two measures. A possible cause of this
      negative correlation is that different thresholds are used in studies to define
      abnormal and normal radiographs because of implicit variations in thresholds that
      occur when radiographers' report plain radiographs. A method that allows for the
      correlation that can exist between pairs of sensitivity and specificity within a
      study using a random effects approach is the bivariate model. When estimates of
      accuracy as a fixed-effects model were pooled separately, radiographers' reported
      plain radiographs in clinical practice at 93% (95% confidence interval (CI) 92
      93%) sensitivity and 98% (95% CI 98-98%) specificity. The bivariate model
      produced the same summary estimates of sensitivity and specificity but with wider
      confidence intervals (93% (95% CI 91-95%) and 98% (95% CI 96-98%), respectively)
      that take into account the heterogeneity beyond chance between studies. This
      method also allowed us to calculate a 95% confidence ellipse around the mean
      values of sensitivity and specificity and a 95% prediction ellipse for individual
      values of sensitivity and specificity. The bivariate model is an improvement on
      pooling sensitivity and specificity separately when there is a threshold effect,
      and it is the preferred method of choice.

PMID- 19153190
TI  - Glycine-extended gastrin inhibits apoptosis in Barrett's oesophageal and
      oesophageal adenocarcinoma cells through JAK2/STAT3 activation.
AB  - Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) are regarded as
      complications of gastro-oesophageal reflux disease, although all the factors that
      contribute to the development of these lesions are unknown. Acid suppressive
      drugs are widely used for symptomatic therapy of reflux disease but may induce
      hypersecretion of gastrin peptides. Amidated gastrin (G-17) has been shown to be
      a growth factor for OAC cells. We have examined the effects of glycine-extended
      gastrin (G-Gly), an alternative product of progastrin processing on apoptosis in
      the QhERT Barrett's oesophageal cell line and OE33 and BIC-1 OAC cells. G-Gly
      inhibited serum-starvation and camptothecin-induced apoptosis in all three cell
      lines, G-17 was only effective in OE33 cells. By contrast to the effects of G-17,
      the anti-apoptotic effect of G-Gly was independent of both the CCK(2) receptor
      and cyclo-oxygenase-2 activity. G-Gly stimulated JAK2 phosphorylation and kinase
      activity and JAK2-dependent STAT3 phosphorylation and transcriptional activity. G
      Gly also increased mRNA and protein levels of the anti-apoptotic proteins
      survivin and BCL2L1 but did not affect the levels of BAD, BAX or BCL-2. Novel
      small molecule inhibitors of JAK2 and STAT3 as well as STAT3 siRNA blocked the
      anti-apoptotic effects of G-Gly and inhibited the induction of survivin and
      BCL2L1 in OE33 cells. We conclude that G-Gly inhibits apoptosis in BO and OAC via
      mechanisms distinct from those activated by G-17 and involving JAK2 and STAT3
      activation. Release of gastrin peptides in response to acid suppressive therapy
      may adversely influence the dynamics of the epithelium in BO.

PMID- 19153191
TI  - Effects of oviductal fluid on the development, quality, and gene expression of
      porcine blastocysts produced in vitro.
AB  - In mammals, fertilization and early pre-implantation development occur in the
      oviduct. Previous results obtained in our laboratory have identified specific
      molecules in the oviduct that affect porcine sperm-egg interactions. The aim of
      the present study was to determine whether the contact between oocytes and
      oviductal fluid also affect embryo development, quality, and gene expression. In
      vitro matured porcine oocytes were exposed to bovine oviductal fluid (bOF) for 30
      min prior to fertilization. Cleavage and blastocyst development rates were
      significantly higher from bOF-treated oocytes than from untreated oocytes.
      Blastocysts obtained from bOF-treated oocytes had significantly greater total
      cell numbers than those obtained from untreated oocytes. Using real-time PCR,
      grade 1 (very good morphological quality) and grade 2 (good morphological
      quality) blastocysts were analyzed for gene transcripts related to apoptosis
      (BAX, BCL2L1), mitochondrial DNA (mtDNA) transcription/replication (POLG, POLG2,
      and TFAM), blastomere connection and morula compaction (GJA1), and blastocyst
      formation and pluripotency (POU5F1). We found that the entire set of genes
      analyzed was differentially expressed between grade 1 and 2 blastocysts.
      Furthermore, bOF treatment reduced the ratio of BAX to BCL2L1 transcripts and
      enhanced the abundance of TFAM transcripts in grade 2 blastocysts. Not only do
      these findings demonstrate that factors within the bOF act on porcine oocytes
      both quickly and positively, but they also suggest that such factors could
      promote embryo development and quality by protecting them against adverse impacts
      on mtDNA transcription/replication and apoptosis induced by the culture
      environment.

PMID- 19153192
TI  - Analysis of DNA methylation of multiple genes in microdissected cells from
      formalin-fixed and paraffin-embedded tissues.
AB  - A procedure for simultaneous quantification of DNA methylation of several genes
      in minute amounts of sample material was developed and applied to microdissected
      formalin-fixed and paraffin-embedded breast tissues. The procedure is comprised
      of an optimized bisulfite treatment protocol suitable for samples containing only
      few cells, a multiplex preamplification and subsequent locus specific
      reamplification, and a novel quantitative bisulfite sequencing method based on
      the incorporation of a normalization domain into the PCR product. A real-time PCR
      assay amplifying repetitive elements was established to quantify low amounts of
      bisulfite-treated DNA. Ten prognostic and diagnostic epigenetic breast cancer
      biomarkers (PITX2, RASSF1A, PLAU, LHX3, PITX3, LIMK1, SLITRK1, SLIT2, HS3ST2, and
      TFF1) were analyzed in tissue samples obtained from two patients with invasive
      ductal carcinoma of the breast. The microdissected samples were obtained from
      several areas within the tumor tissue, including intraductal and invasive
      carcinoma, adenosis, and normal ductal epithelia of adjacent normal tissue, as
      well as stroma, tumor infiltrating lymphocytes, and adipose tissue. Overall,
      reliable quantification was possible for all genes. For most genes, increased DNA
      methylation in invasive and intraductal carcinoma cells compared with other
      tissue components was observed. For TFF1, decreased methylation levels were
      observed in tumor cells.

PMID- 19153193
TI  - Characterization of the mechanisms involved in the increased renal elimination of
      bromosulfophthalein during cholestasis: involvement of Oatp1.
AB  - The kidneys and liver are the major routes for organic anion elimination. We have
      recently shown that acute obstructive jaundice is associated with increased
      systemic and renal elimination of two organic anions, p-aminohippurate and
      furosemide, principally excreted through urine. This study examined probable
      adaptive mechanisms involved in renal elimination of bromosulfophthalein (BSP), a
      prototypical organic anion principally excreted in bile, in rats with acute
      obstructive jaundice. Male Wistar rats underwent bile duct ligation (BDL rats).
      Pair-fed sham-operated rats served as controls. BSP renal clearance was performed
      by conventional techniques. Renal organic anion-transporting polypeptide 1
      (Oatp1) expression was evaluated by immunoblotting and IHC. Excreted, filtered,
      and secreted loads of BSP were all higher in BDL rats compared with Sham rats.
      The higher BSP filtered load resulted from the increase in plasma BSP
      concentration in BDL rats, because glomerular filtration rate showed no
      difference with the Sham group. The increase in the secreted load might be
      explained by the higher expression of Oatp1 observed in apical membranes from
      kidneys of BDL animals. This likely adaptation to hepatic injury, specifically in
      biliary components elimination, might explain, at least in part, the huge
      increase in BSP renal excretion observed in this experimental model.

PMID- 19153194
TI  - Disruption of Nfic causes dissociation of odontoblasts by interfering with the
      formation of intercellular junctions and aberrant odontoblast differentiation.
AB  - We reported previously that Nfic-deficient mice exhibit short and abnormal molar
      roots and severely deformed incisors. The objective of this study is to address
      the mechanisms responsible for these changes using morphological, IHC, and RT-PCR
      analysis. Nfic-deficient mice exhibited aberrant odontoblasts and abnormal dentin
      formation in molar roots and the labial crown analog of incisors. The most
      striking changes observed in these aberrant odontoblasts were the loss of
      intercellular junctions and the decreased expression of ZO-1 and occludin. As a
      result, they became dissociated, had a round shape, and lost their cellular
      polarity and arrangement as a sheet of cells. Furthermore, the dissociated
      odontoblasts became trapped in dentin-like mineralized tissue, resembling
      osteodentin in the overall morphology. These findings suggest that loss of the
      Nfic gene interferes with the formation of intercellular junctions that causes
      aberrant odontoblast differentiation and abnormal dentin formation. Collectively,
      these changes in odontoblasts contributed to development of molars with short and
      abnormal roots in Nfic-deficient mice.

PMID- 19153196
TI  - Tight junction proteins in human Schwann cell autotypic junctions.
AB  - Tight junctions (TJs) form physical barriers in various tissues and regulate
      paracellular transport of ions, water, and molecules. Myelinating Schwann cells
      form highly organized structures, including compact myelin, nodes of Ranvier,
      paranodal regions, Schmidt-Lanterman incisures, periaxonal cytoplasmic collars,
      and mesaxons. Autotypic TJs are formed in non-compacted myelin compartments
      between adjacent membrane lamellae of the same Schwann cell. Using indirect
      immunofluorescence and RT-PCR, we analyzed the expression of adherens junction (E
      cadherin) and TJ [claudins, zonula occludens (ZO)-1, occludin] components in
      human peripheral nerve endoneurium, showing clear differences with published
      rodent profiles. Adult nerve paranodal regions contained E-cadherin, claudin-1,
      claudin-2, and ZO-1. Schmidt-Lanterman incisures contained E-cadherin, claudin-1,
      claudin-2, claudin-3, claudin-5, ZO-1, and occludin. Mesaxons contained E
      cadherin, claudin-1, claudin-2, claudin-3, ZO-1, and occludin. None of the
      proteins studied were associated with nodal inter-Schwann cell junctions. Fetal
      nerve expression of claudin-1, claudin-3, ZO-1, and occludin was predominantly
      punctate, with a mesaxonal labeling pattern, but paranodal (ZO-1, claudin-3) and
      Schmidt-Lanterman incisure (claudins-1 and -3) expression profiles typical of
      compact myelin were visible by gestational week 37. The clear differences
      observed between human and published rodent nerve profiles emphasize the
      importance of human studies when translating the results of animal models to
      human diseases.

PMID- 19153195
TI  - Gastric mucus alterations associated with murine Helicobacter infection.
AB  - The C57BL/6 mouse has been shown to develop gastric adenocarcinoma after
      Helicobacter felis infection. This model was used to determine whether mucin and
      trefoil factor (TFF) expression after infection was altered in a similar fashion
      to the changes seen in the protective gastric mucus layer of the human stomach
      after H. pylori infection. Our results indicate that this mouse model mimics many
      of the changes seen after human H. pylori infection, including increased
      expression of muc4 and muc5b and loss of muc5ac. These alterations in mucin
      expression occurred as early as 4 weeks postinfection, before the development of
      significant mucous metaplasia or gastric dysplasia. The decrease in muc5ac
      expression occurred only in the body of the stomach and was not secondary to the
      adaptive immune response to infection, because a similar decrease in expression
      was seen after infection of B6.Rag-1(-/-) mice, which lack B and T cells.
      Intriguingly, the increased expression of Muc4 and Muc5b in infected C57BL/6 mice
      was not seen in the infected B6.Rag-1(-/-) mice. Because B6.Rag-1(-/-) mice do
      not develop gastric pathology after H. felis infection, these findings point to
      the potential role of Muc4 and Muc5b in disease progression. This manuscript
      contains online supplemental material at http://www.jhc.org. Please visit this
      article online to view these materials.

PMID- 19153197
TI  - Exposure variability and image quality in computed radiography.
AB  - PURPOSE: To evaluate the effect of a wide range of exposure techniques on the
      overall quality of the computed radiography (CR) image. METHODS: A Fuji FCR 1
      Shot QC Phantom was exposed to mAs values ranging from 1 to 125, yielding 8
      exposure groups. Five CR imaging plates were exposed, processed and printed for
      each exposure group. Image quality was evaluated by measuring the optical
      density, density differences and number of line pairs visualized. RESULTS: The
      findings indicate that variability in radiation exposure to the CR imaging plate
      does not adversely affect the quality of the digital image. Optical density and
      low-density differences were stable throughout the wide range of exposures.
      Radiographic contrast appeared to decrease for the high-density differences when
      exposed to higher-than-needed exposures, and resolution appeared to be
      compromised at extreme low-radiation exposures. CONCLUSION: The results of this
      experimental study are consistent with the digital imaging literature in that a
      radiation exposure technique above or below the optimum level will produce a
      diagnostic-quality image. Radiographers must become more knowledgeable about
      digital imaging systems so they can produce quality images with the least amount
      of exposure to their patients.

PMID- 19153198
TI  - Compassion: the vital element.

PMID- 19153199
TI  - Preventing drug-resistant infections in health care.
AB  - Health care-acquired infections (HAIs) affect millions of health care workers and
      patients every year and are becoming increasingly resistant to common treatments.
      These dangerous infections are largely preventable, but are created primarily by
      the inappropriate administration of antibiotics and spread by inadequate
      infection control practices by health care workers. Many institutions currently
      do not report or effectively control HAI outbreaks, but the regulatory climate is
      changing and medical imaging personnel have an important role in preventing the
      spread of HAIs. This article introduces contamination types and transmission
      facets of the HAI problem. Physical reservoirs in the health care environment are
      identified and the epidemiology, surveillance and control of emerging multidrug
      resistant bacteria are reviewed.

PMID- 19153200
TI  - Thyroid cancer in adults.
AB  - This article provides an overview of thyroid cancer, an increasingly common but
      highly treatable disease. Types of thyroid cancer, staging systems, diagnostic
      techniques and treatment options are discussed.

PMID- 19153201
TI  - The augmented breast.
AB  - Augmented breasts present special challenges for medical imaging. This article
      reviews mammographic techniques and other imaging modalities used to screen for
      and diagnose breast disease in patients with augmented breasts. Other topics
      include different types of breast implants and surgical techniques used for
      implantation, as well as overviews of breast disease and mammographic reporting.

PMID- 19153202
TI  - Molecular imaging detects breast cancer.

PMID- 19153203
TI  - Faculty guide to rubrics.

PMID- 19153205
TI  - Evidence based medical imaging (EBMI).
AB  - BACKGROUND: The evidence based paradigm was first described about a decade ago.
      Previous authors have described a framework for the application of evidence based
      medicine which can be readily adapted to medical imaging practice. PURPOSE: This
      paper promotes the application of the evidence based framework in both the
      justification of the choice of examination type and the optimisation of the
      imaging technique used. METHODS: The framework includes five integrated steps:
      framing a concise clinical question; searching for evidence to answer that
      question; critically appraising the evidence; applying the evidence in clinical
      practice; and, evaluating the use of revised practices. RESULTS: This paper
      illustrates the use of the evidence based framework in medical imaging (that is,
      evidence based medical imaging) using the examples of two clinically relevant
      case studies. In doing so, a range of information technology and other resources
      available to medical imaging practitioners are identified with the intention of
      encouraging the application of the evidence based paradigm in radiography and
      radiology. CONCLUSION: There is a perceived need for radiographers and
      radiologists to make greater use of valid research evidence from the literature
      to inform their clinical practice and thus provide better quality services.

PMID- 19153206
TI  - Easing the lateral hip exam.

PMID- 19153207
TI  - Patient page. Upper extremity radiography.

PMID- 19153208
TI  - Analysis of signaling pathways related to cell proliferation stimulated by
      insulin analogs in human mammary epithelial cell lines.
AB  - Insulin and insulin analogs stimulate proliferation of human mammary epithelial
      cells. We identified and analyzed the signaling pathways related to cell
      proliferation induced by regular insulin and by four insulin analogs presently
      approved for therapeutical use. Benign and malignant mammary cell lines showing
      different insulin receptor (IR) and IGF-I receptor (IGF-IR) expression patterns
      were studied. Cell proliferation was studied by crystal violet staining (BrdU
      FACS analysis). Activation of insulin and IGF signaling pathways was studied by
      analysis of the phosphorylation status of IGF-IR and of key signaling proteins of
      the phosphoinositide 3-kinase (PI3K)/Akt and MAP kinase pathways, by the use of
      specific PI3K and MAP kinase inhibitors, and by silencing of IR and IGF-IR.
      Lantus stimulated the growth of MCF7 cells, which show high IGF-IR/IR ratio,
      significantly at 0.3 nmol/l, while regular insulin (Actrapid and bovine insulin)
      and other insulin analogs (Novorapid, Humalog, and Levemir) stimulated cell
      growth at 1.5-15 nmol/l concentrations. No difference between Lantus and the
      other insulin analogs was observed regarding growth stimulation of MCF10A cells
      showing low IGF-IR/IR ratio. Growth stimulation of MCF7 cells by Lantus was
      mainly due to strong activation of the IGF-IR and the MAP kinase pathway. Regular
      insulin and other insulin analogs tested activated mainly the IR and the PI3K/Akt
      pathway. We conclude that unlike regular insulin and other insulin analogs,
      Lantus strongly activates the IGF-IR and the MAP kinase pathway in MCF7 cells and
      is a strong mitogen for cells characterized by a high-IGF-IR/IR ratio.

PMID- 19153209
TI  - Array-comparative genomic hybridization in sporadic benign pheochromocytomas.
AB  - Pheochromocytomas (PCC) are catecholamine-producing tumors arising from the
      adrenal medulla that occur either sporadically or in the context of hereditary
      cancer syndromes, such as multiple endocrine neoplasia type 2 (MEN2), von Hippel
      Lindau disease (VHL), neurofibromatosis type 1, and the PCC-paraganglioma
      syndrome. Conventional comparative genomic hybridization studies have shown loss
      of 1p and 3q in the majority of sporadic and MEN2-related PCC, and 3p and 11p
      loss in VHL-related PCC. The development of a submegabase tiling resolution array
      enabled us to perform a genome-wide high-resolution analysis of 36 sporadic
      benign PCC. The results show that there are two distinct patterns of
      abnormalities in these sporadic PCC, one consisting of loss of 1p with or without
      concomitant 3q loss in 20/36 cases (56%), the other characterized by loss of 3p
      with or without concomitant 11p loss in 11/36 (31%). In addition, we found loss
      of chromosome 22q at high frequency (35%), as well as the novel finding of high
      frequency chromosome 21q loss (21%). We conclude that there appear to be two
      subgroups of benign sporadic PCC, one of which has a pattern of chromosomal
      abnormalities that is comparable with PCC from patients with MEN2 and the other
      that is comparable with the PCC that arise in patients with VHL disease. In
      addition, genes on 21q and 22q might play a more important role in PCC
      pathogenesis than had been assumed thus far.

PMID- 19153210
TI  - Obestatin stimulates Akt signalling in gastric cancer cells through beta-arrestin
      mediated epidermal growth factor receptor transactivation.
AB  - Obestatin was identified as a gut peptide encoded by the ghrelin gene that
      interacts with the G protein-coupled receptor, GPR39. In this work, a sequential
      analysis of its transmembrane signalling pathway has been undertaken to
      characterize the intracellular mechanisms responsible for Akt activation. The
      results show that Akt activation requires the phosphorylation of T308 in the A
      loop by the phosphoinositide-dependent kinase 1 (PDK1) and S473 within the HM by
      the mammalian target of rapamycin (mTOR) kinase complex 2 (mTORC2: Rictor, mLST8,
      mSin1, mTOR kinase) with participation neither of G(i)(/o)-protein nor Gbetagamma
      dimers. Obestatin induces the association of GPR39/beta-arrestin 1/Src signalling
      complex resulting in the transactivation of the epidermal growth factor receptor
      (EGFR) and downstream Akt signalling. Upon administration of obestatin,
      phosphorylation of mTOR (S2448) and p70S6K1 (T389) rise with a time course that
      parallels that of Akt activation. Based on the experimental data obtained, a
      signalling pathway involving a beta-arrestin 1 scaffolding complex and EGFR to
      activate Akt signalling is proposed.

PMID- 19153211
TI  - Azacitidine improves antitumor effects of docetaxel and cisplatin in aggressive
      prostate cancer models.
AB  - One of the major obstacles in the treatment of hormone-refractory prostate cancer
      (HRPC) is the development of chemoresistant tumors. The aim of this study is to
      evaluate the role of azacitidine as chemosensitizing agent in association with
      docetaxel (DTX) and cisplatin using two models of aggressive prostate cancer, the
      22rv1, and PC3 cell lines. Azacitidine shows antiproliferative effects associated
      with increased proportion of cells in G0/G1 and evident apoptosis in 22rv1 cells
      and increased proportion of cells in G2/M phase with the absence of acute cell
      killing in PC3 cells. In vivo, azacitidine (0.8 mg/kg i.p.) reduced tumor
      proliferation and induced apoptosis in both xenografts upmodulating the
      expression of p16INKA, Bax, Bak, p21/WAF1, and p27/KIP1, and inhibiting the
      activation of Akt activity and the expression of cyclin D1, Bcl-2, and Bcl-XL. In
      vitro treatments with azacitidine lead to upregulation of cleaved caspase 3 and
      PARP. BCl2 antagonists, such as HA-14-1, enhanced the effects of azacitidine in
      these two prostate cancer models. In addition, azacitidine showed synergistic
      effects with both DTX and cisplatin. In vivo this agent caused tumor growth delay
      without complete regression in xenograft systems. Azacitidine sensitized PC3 and
      22rv1 xenografts to DTX and cisplatin treatments. These combinations were also
      tolerable in mice and superior to either agent alone. As DTX is the standard
      first-line chemotherapy for HRPC, the development of DTX-based combination
      therapies is of great interest in this disease stage. Our results provide a
      rationale for clinical trials on combination treatments with azacitidine in
      patients with hormone-refractory and chemoresistant prostate tumors.

PMID- 19153213
TI  - Invited commentary: built environment and obesity among older adults--can
      neighborhood-level policy interventions make a difference?
AB  - Obesity is more prevalent and its consequences severe among middle-aged and older
      adults. Efforts to understand and address neighborhood-level causes of obesity in
      this population offer the potential to enhance health and reduce the costs of
      obesity for everyone. The accompanying paper by Li et al. (Am J Epidemiol.
      2009;169(4):401-408) presents new data on the apparently significant interaction
      between neighborhood and individual characteristics on 1-year change in body
      weight and waist circumference. Despite methodological limitations in
      measurement, this paper supports the importance of future research that considers
      the complex relation between people and where they live. Efforts to design
      neighborhood-level policy interventions to effectively address the problem of
      obesity will require greater interdisciplinary collaboration.

PMID- 19153214
TI  - Built environment and 1-year change in weight and waist circumference in middle
      aged and older adults: Portland Neighborhood Environment and Health Study.
AB  - This study examined neighborhood built environment characteristics (fast-food
      restaurant density, walkability) and individual eating-out and physical activity
      behaviors in relation to 1-year change in body weight among adults 50-75 years of
      age at baseline. The authors surveyed 1,145 residents recruited from 120
      neighborhoods in Portland, Oregon. During the 1-year follow-up (2006-2007 to 2007
      2008), mean weight increased by 1.72 kg (standard deviation, 4.3) and mean waist
      circumference increased by 1.76 cm (standard deviation, 5.6). Multilevel analyses
      revealed that neighborhoods with a high density of fast-food outlets were
      associated with increases of 1.40 kg in weight (P<0.05) and 2.04 cm in waist
      circumference (P<0.05) among residents who visited fast-food restaurants
      frequently. In contrast, high-walkability neighborhoods were associated with
      decreases of 1.2 kg in weight (P<0.05) and 1.57 cm in waist circumference
      (P<0.05) among residents who increased their levels of vigorous physical activity
      during the 1-year assessment period. Findings point to the negative influences of
      the availability of neighborhood fast-food outlets and individual unhealthy
      eating behaviors that jointly affect weight gain; however, better neighborhood
      walkability and increased levels of physical activity are likely to be associated
      with maintaining a healthy weight over time.

PMID- 19153215
TI  - Vascular function, inflammation, and variations in cardiac autonomic responses to
      particulate matter among welders.
AB  - Patients with health conditions associated with impaired vascular function and
      inflammation may be more susceptible to the adverse health effects of fine
      particulate (particulate matter with a mass median aerodynamic diameter of </=2.5
      mum (PM(2.5))) exposure. In 2006, the authors conducted a panel study to
      investigate directly whether vascular function and inflammation (assessed by C
      reactive protein) modify PM(2.5)-associated reductions in heart rate variability
      among 23 young male workers (mean age, 40 years) from Massachusetts. Concurrent
      24-hour ambulatory electrocardiogram and personal PM(2.5) exposure information
      was collected over a total of 36 person-days, including either or both welding
      and nonwelding days. Linear mixed models were used to examine the 5-minute
      standard deviation of normal-to-normal intervals (SDNN) in relation to the moving
      PM(2.5) averages in the preceding 1-4 hours. C-reactive protein levels and 3
      measures of vascular function (augmentation index, mean arterial pressure, and
      pulse pressure) were determined at baseline. The authors observed an inverse
      association between the 1-hour PM(2.5) and 5-minute SDNN. Greater SDNN declines
      were observed among those with C-reactive protein (P(interaction) < 0.001) and
      augmentation index (P = 0.06) values at or above the 75th percentile and pulse
      pressure values below the 75th percentile (P < 0.001). Systemic inflammation and
      poorer vascular function appear to aggravate particle-related declines in heart
      rate variability among workers.

PMID- 19153216
TI  - Different methods of balancing covariates leading to different effect estimates
      in the presence of effect modification.
AB  - A number of covariate-balancing methods, based on the propensity score, are
      widely used to estimate treatment effects in observational studies. If the
      treatment effect varies with the propensity score, however, different methods can
      give very different answers. The authors illustrate this effect by using data
      from a United Kingdom-based registry of subjects treated with anti-tumor necrosis
      factor drugs for rheumatoid arthritis. Estimates of the effect of these drugs on
      mortality varied from a relative risk of 0.4 (95% confidence interval: 0.16,
      0.91) to a relative risk of 1.3 (95% confidence interval: 0.8, 2.25), depending
      on the balancing method chosen. The authors show that these differences were due
      to a combination of an interaction between propensity score and treatment effect
      and to differences in weighting subjects with different propensity scores. Thus,
      the methods are being used to calculate average treatment effects in populations
      with very different distributions of effect-modifying variables, resulting in
      different overall estimates. This phenomenon highlights the importance of careful
      selection of the covariate-balancing method so that the overall estimate has a
      meaningful interpretation.

PMID- 19153219
TI  - The American Society for Cell Biology, 48th Annual Meeting San Francisco, CA,
      December 13-17, 2008.

PMID- 19153220
TI  - Essential and unique roles of PIP5K-gamma and -alpha in Fcgamma receptor-mediated
      phagocytosis.
AB  - The actin cytoskeleton is dynamically remodeled during Fcgamma receptor
      (FcgammaR)-mediated phagocytosis in a phosphatidylinositol (4,5)-bisphosphate
      (PIP(2))-dependent manner. We investigated the role of type I
      phosphatidylinositol 4-phosphate 5-kinase (PIP5K) gamma and alpha isoforms, which
      synthesize PIP(2), during phagocytosis. PIP5K-gamma-/- bone marrow-derived
      macrophages (BMM) have a highly polymerized actin cytoskeleton and are defective
      in attachment to IgG-opsonized particles and FcgammaR clustering. Delivery of
      exogenous PIP(2) rescued these defects. PIP5K-gamma knockout BMM also have more
      RhoA and less Rac1 activation, and pharmacological manipulations establish that
      they contribute to the abnormal phenotype. Likewise, depletion of PIP5K-gamma by
      RNA interference inhibits particle attachment. In contrast, PIP5K-alpha knockout
      or silencing has no effect on attachment but inhibits ingestion by decreasing
      Wiskott-Aldrich syndrome protein activation, and hence actin polymerization, in
      the nascent phagocytic cup. In addition, PIP5K-gamma but not PIP5K-alpha is
      transiently activated by spleen tyrosine kinase-mediated phosphorylation. We
      propose that PIP5K-gamma acts upstream of Rac/Rho and that the differential
      regulation of PIP5K-gamma and -alpha allows them to work in tandem to modulate
      the actin cytoskeleton during the attachment and ingestion phases of
      phagocytosis.

PMID- 19153221
TI  - Reversible binding and rapid diffusion of proteins in complex with inositol
      lipids serves to coordinate free movement with spatial information.
AB  - Polyphosphoinositol lipids convey spatial information partly by their
      interactions with cellular proteins within defined domains. However, these
      interactions are prevented when the lipids' head groups are masked by the
      recruitment of cytosolic effector proteins, whereas these effectors must also
      have sufficient mobility to maximize functional interactions. To investigate
      quantitatively how these conflicting functional needs are optimized, we used
      different fluorescence recovery after photobleaching techniques to investigate
      inositol lipid-effector protein kinetics in terms of the real-time dissociation
      from, and diffusion within, the plasma membrane. We find that the protein-lipid
      complexes retain a relatively rapid ( approximately 0.1-1 microm(2)/s) diffusion
      coefficient in the membrane, likely dominated by protein-protein interactions,
      but the limited time scale (seconds) of these complexes, dictated principally by
      lipid-protein interactions, limits their range of action to a few microns.
      Moreover, our data reveal that GAP1(IP4BP), a protein that binds PtdIns(4,5)P(2)
      and PtdIns(3,4,5)P(3) in vitro with similar affinity, is able to "read"
      PtdIns(3,4,5)P(3) signals in terms of an elongated residence time at the
      membrane.

PMID- 19153222
TI  - Antagonism between Smad1 and Smad2 signaling determines the site of distal
      visceral endoderm formation in the mouse embryo.
AB  - The anterior-posterior axis of the mouse embryo is established by formation of
      distal visceral endoderm (DVE) and its subsequent migration. The precise
      mechanism of DVE formation has remained unknown, however. Here we show that bone
      morphogenetic protein (BMP) signaling plays dual roles in DVE formation. BMP
      signaling is required at an early stage for differentiation of the primitive
      endoderm into the embryonic visceral endoderm (VE), whereas it inhibits DVE
      formation, restricting it to the distal region, at a later stage. A Smad2
      activating factor such as Activin also contributes to DVE formation by generating
      a region of VE positive for the Smad2 signal and negative for Smad1 signal. DVE
      is thus formed at the distal end of the embryo, the only region of VE negative
      for the Smad1 signal and positive for Smad2 signal. An inverse relation between
      the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests
      an involvement of antagonism between Smad1- and Smad2-mediated signaling.

PMID- 19153223
TI  - Histone hypercitrullination mediates chromatin decondensation and neutrophil
      extracellular trap formation.
AB  - Peripheral blood neutrophils form highly decondensed chromatin structures, termed
      neutrophil extracellular traps (NETs), that have been implicated in innate immune
      response to bacterial infection. Neutrophils express high levels of
      peptidylarginine deiminase 4 (PAD4), which catalyzes histone citrullination.
      However, whether PAD4 or histone citrullination plays a role in chromatin
      structure in neutrophils is unclear. In this study, we show that the
      hypercitrullination of histones by PAD4 mediates chromatin decondensation.
      Histone hypercitrullination is detected on highly decondensed chromatin in HL-60
      granulocytes and blood neutrophils. The inhibition of PAD4 decreases histone
      hypercitrullination and the formation of NET-like structures, whereas PAD4
      treatment of HL-60 cells facilitates these processes. The loss of heterochromatin
      and multilobular nuclear structures is detected in HL-60 granulocytes after PAD4
      activation. Importantly, citrullination of biochemically defined avian nucleosome
      arrays inhibits their compaction by the linker histone H5 to form higher order
      chromatin structures. Together, these results suggest that histone
      hypercitrullination has important functions in chromatin decondensation in
      granulocytes/neutrophils.

PMID- 19153224
TI  - Coinfection with two closely related alphaherpesviruses results in a highly
      diversified recombination mosaic displaying negative genetic interference.
AB  - Phylogenetic studies of the emergence and spread of natural recombinants in
      herpesviruses infecting humans and animals have been reported recently. However,
      despite an ever-increasing amount of evidence of recombination in herpesvirus
      history, the recombination process and the consequences on the genetic diversity
      of the progeny remain poorly characterized. We addressed this issue by using
      multiple single-nucleotide polymorphisms (SNPs) differentiating the two subtypes
      of an alphaherpesvirus, bovine herpesvirus 1 (BoHV-1). Analysis of a large sample
      of progeny virions obtained in a single growth cycle of coinfected BoHV-1 strains
      provided a prospective investigation of the recombination dynamics by using SNPs
      as recombination markers. We found that the simultaneous infection with two
      closely related herpesviruses results in a highly diversified recombination
      mosaic. From the analysis of multiple recombinants arising in the progeny, we
      provide the first evidence of genetic interference influencing the recombination
      process in herpesviruses. In addition, we report striking differences in the
      levels of recombination frequency observed along the BoHV-1 genome. With
      particular emphasis on the genetic structure of a progeny virus population rising
      in vitro, our data show to which extent recombination participates to the genetic
      diversification of herpesviruses.

PMID- 19153225
TI  - Are human P[14] rotavirus strains the result of interspecies transmissions from
      sheep or other ungulates that belong to the mammalian order Artiodactyla?
AB  - A limited number of human G6P[14] rotavirus strains that cause gastroenteritis in
      humans have been isolated in Europe and Australia. The complete genome sequences
      were determined for five of these human strains--B10925-97 (isolated in Belgium
      in 1997), 111/05-27 (Italy, 2005), PA169 (Italy, 1987), MG6 (Australia, 1993),
      and Hun5 (Hungary, 1997)--and their genetic relatedness to animal rotavirus
      strains was evaluated by sequencing the complete genome of the sheep rotavirus
      OVR762 (G8P[14]; Spain, 2002), the guanaco (Lama guanicoe) rotavirus strains
      Arg/Chubut/99 and Arg/Rio Negro/98 (G8P[14] and G8P[1], respectively; Argentina,
      1999 and 1998), the sable antelope strain RC-18/08 (G6P[14]; South Africa, 2008),
      and the bovine rotavirus strain Arg/B383/98 (G15P[11]; Argentina, 1998). These
      analyses revealed an overall consensus genomic constellation (G6/G8)-P[14]-I2
      (R2/R5)-C2-M2-(A3/A11)-N2-T6-(E2/E12)-H3, together with a few gene reassortments,
      and the phylogenetic analyses confirmed that the P[14] human strains evaluated in
      this study were closely related to rotavirus strains isolated from sheep, cattle,
      goats, guanacos, and antelopes and to rabbits (albeit to a lesser extent),
      suggesting that one (or more) of these animal species might be the source of the
      human G6P[14] strains. The main feature of the genotype and phylogenetic analyses
      was the close overall genomic relatedness between the five human G6P[14]
      rotavirus strains and the ovine and antelope rotavirus strains. Taken together,
      these data strongly suggest a common origin for the human P[14] strains and those
      of the even-toed ungulates belonging to the mammalian order Artiodactyla, with
      sheep probably playing a key role in the interspecies transmission responsible
      for the introduction of P[14] rotavirus strains into the human population.

PMID- 19153226
TI  - Characterization of Lassa virus cell entry and neutralization with Lassa virus
      pseudoparticles.
AB  - The cell entry and humoral immune response of the human pathogen Lassa virus
      (LV), a biosafety level 4 (BSL4) Old World arenavirus, are not well
      characterized. LV pseudoparticles (LVpp) are a surrogate model system that has
      been used to decipher factors and routes involved in LV cell entry under BSL2
      conditions. Here, we describe LVpp, which are highly infectious, with titers
      approaching those obtained with pseudoparticles displaying G protein of vesicular
      stomatitis virus and their the use for the characterization of LV cell entry and
      neutralization. Upon cell attachment, LVpp utilize endocytic vesicles for cell
      entry as described for many pH-dependent viruses. However, the fusion of the LV
      glycoproteins is activated at unusually low pH values, with optimal fusion
      occurring between pH 4.5 and 3, a pH range at which fusion characteristics of
      viral glycoproteins have so far remained largely unexplored. Consistent with a
      shifted pH optimum for fusion activation, we found wild-type LV and LVpp to
      display a remarkable resistance to exposure to low pH. Finally, LVpp allow the
      fast and quantifiable detection of neutralizing antibodies in human and animal
      sera and will thus facilitate the study of the humoral immune response in LV
      infections.

PMID- 19153227
TI  - E7 oncoprotein of novel human papillomavirus type 108 lacking the E6 gene induces
      dysplasia in organotypic keratinocyte cultures.
AB  - The genome organization of the novel human papillomavirus type 108 (HPV108),
      isolated from a low-grade cervical lesion, deviates from those of other HPVs in
      lacking an E6 gene. The three related HPV types HPV103, HPV108, and HPV101 were
      isolated from cervicovaginal cells taken from normal genital mucosa (HPV103) and
      low-grade (HPV108) and high-grade cervical (HPV101) intraepithelial neoplasia (Z.
      Chen, M. Schiffman, R. Herrero, R. DeSalle, and R. D. Burk, Virology 360:447-453,
      2007, and this report). Their unusual genome organization, against the background
      of considerable phylogenetic distance from the other HPV types usually associated
      with lesions of the genital tract, prompted us to investigate whether HPV108 E7
      per se is sufficient to induce the above-mentioned clinical lesions. Expression
      of HPV108 E7 in organotypic keratinocyte cultures increases proliferation and
      apoptosis, focal nuclear polymorphism, and polychromasia. This is associated with
      irregular intra- and extracellular lipid accumulation and loss of the epithelial
      barrier. These alterations are linked to HPV108 E7 binding to pRb and inducing
      its decrease, an increase in PCNA expression, and BrdU incorporation, as well as
      increased p53 and p21(CIP1) protein levels. A delay in keratin K10 expression,
      increased expression of keratins K14 and K16, and loss of the corneal proteins
      involucrin and loricrin have also been noted. These modifications are suggestive
      of infection by a high-risk papillomavirus.

PMID- 19153228
TI  - The major portal of entry of koi herpesvirus in Cyprinus carpio is the skin.
AB  - Koi herpesvirus (KHV), recently designated Cyprinid herpesvirus 3, is the
      causative agent of a lethal disease in koi and common carp. In the present study,
      we investigated the portal of entry of KHV in carp by using bioluminescence
      imaging. Taking advantage of the recent cloning of the KHV genome as a bacterial
      artificial chromosome (BAC), we produced a recombinant plasmid encoding a firefly
      luciferase (LUC) expression cassette inserted in the intergenic region between
      open reading frame (ORF) 136 and ORF 137. Two viral strains were then
      reconstituted from the modified plasmid, the FL BAC 136 LUC excised strain and
      the FL BAC 136 LUC TK revertant strain, including a disrupted and a wild-type
      thymidine kinase (TK) locus, respectively. In vitro, the two recombinant strains
      replicated comparably to the parental FL strain. The FL BAC 136 LUC TK revertant
      strain was shown in vitro to induce a bioluminescent signal allowing the
      detection of single positive cells as early as 24 h postinfection, while in vivo,
      it induced KHV infection in carp that was indistinguishable from that induced by
      the parental FL strain. To identify the KHV portal of entry, carp were analyzed
      by bioluminescence imaging at different times postinfection with the FL BAC 136
      LUC TK revertant strain. These analyses demonstrated that the skin of the fish
      covering the fins and also the body is the major portal of entry for KHV in carp.
      Finally, to further demonstrate the role of the skin as the KHV portal of entry,
      we constructed an original system, nicknamed "U-tube," to perform percutaneous
      infection restricted to the posterior part of the fish. All the data obtained in
      the present study demonstrate that the skin, and not the gills, is the major
      portal of entry for KHV in carp.

PMID- 19153229
TI  - Regulatory T cells promote early influx of CD8+ T cells in the lungs of
      respiratory syncytial virus-infected mice and diminish immunodominance
      disparities.
AB  - In addition to regulating autoimmunity and antitumor immunity, CD4(+) CD25(+)
      FoxP3(+) natural regulatory T (Treg) cells are global regulators of adaptive
      immune responses. Depletion of these cells with the anti-CD25 antibody PC61 prior
      to primary respiratory syncytial virus (RSV) infection was partial but had
      several effects on the RSV-specific CD8(+) response in a hybrid mouse model.
      Mediastinal lymph node and spleen epitope-specific CD8(+) T-cell responses were
      enhanced in Treg-cell-depleted mice at all time points following infection, but
      responses of Treg-cell-depleted lung show a strikingly different pattern than
      lymphoid organ responses, with an initial delay in the CD8(+) T-cell response.
      The delay in the CD8(+) T-cell response correlated with a delay both in the early
      phase of viral clearance and in illness in Treg-cell-depleted mice compared to
      isotype-treated controls. The lungs of Treg-cell-depleted mice were shown to have
      increased lung chemokine and cytokine levels 7 days postinfection despite lower
      CD8(+) T-cell responses. Following the early delay in the lung response, CD8(+) T
      cell responses at later infection time points were enhanced and increased the
      severity of illness in depleted mice. Finally, decreasing regulatory T-cell
      control of the CD8(+) T-cell response had a greater effect on response of the
      dominant K(d)-restricted M2 epitope consisting of amino acids 82 to 90 (K(d)M2(82
      90)) than on the subdominant D(b)M(187-195) epitope response, indicating that
      regulatory T cells modulate immunodominance disparities in epitope-specific
      CD8(+) T-cell responses following primary RSV infection.

PMID- 19153230
TI  - HLA-associated viral mutations are common in human immunodeficiency virus type 1
      elite controllers.
AB  - Elite controllers (EC) of human immunodeficiency virus type 1 (HIV-1) maintain
      viremia below the limit of detection without antiretroviral treatment. Virus
      specific cytotoxic CD8(+) T lymphocytes are believed to play a crucial role in
      viral containment, but the degree of immune imprinting and compensatory mutations
      in EC is unclear. We obtained plasma gag, pol, and nef sequences from HLA-diverse
      subjects and found that 30 to 40% of the predefined HLA-associated polymorphic
      sites show evidence of immune selection pressure in EC, compared to approximately
      50% of the sites in chronic progressors. These data indicate ongoing viral
      replication and escape from cytotoxic T lymphocytes are present even in strictly
      controlled HIV-1 infection.

PMID- 19153231
TI  - Ebola virus protein VP35 impairs the function of interferon regulatory factor
      activating kinases IKKepsilon and TBK-1.
AB  - The Ebola virus (EBOV) VP35 protein antagonizes the early antiviral alpha/beta
      interferon (IFN-alpha/beta) response. We previously demonstrated that VP35
      inhibits the virus-induced activation of the IFN-beta promoter by blocking the
      phosphorylation of IFN-regulatory factor 3 (IRF-3), a transcription factor that
      is crucial for the induction of IFN-alpha/beta expression. Furthermore, VP35
      blocks IFN-beta promoter activation induced by any of several components of the
      retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5
      (MDA-5)-activated signaling pathways including RIG-I, IFN-beta promoter
      stimulator 1 (IPS-1), TANK-binding kinase 1 (TBK-1), and IkappaB kinase epsilon
      (IKKepsilon). These results suggested that VP35 may target the IRF kinases TBK-1
      and IKKepsilon. Coimmunoprecipitation experiments now demonstrate physical
      interactions of VP35 with IKKepsilon and TBK-1, and the use of an IKKepsilon
      deletion construct further demonstrates that the amino-terminal kinase domain of
      IKKepsilon is sufficient for interactions with either IRF-3 or VP35. In vitro,
      either IKKepsilon or TBK-1 phosphorylates not only IRF-3 but also VP35. Moreover,
      VP35 overexpression impairs IKKepsilon-IRF-3, IKKepsilon-IRF-7, and IKKepsilon
      IPS-1 interactions. Finally, lysates from cells overexpressing IKKepsilon contain
      kinase activity that can phosphorylate IRF-3 in vitro. When VP35 is expressed in
      the IKKepsilon-expressing cells, this kinase activity is suppressed. These data
      suggest that VP35 exerts its IFN-antagonist function, at least in part, by
      blocking necessary interactions between the kinases IKKepsilon and TBK-1 and
      their normal interaction partners, including their substrates, IRF-3 and IRF-7.

PMID- 19153232
TI  - Severe acute respiratory syndrome coronavirus nsp9 dimerization is essential for
      efficient viral growth.
AB  - The severe acute respiratory syndrome coronavirus (SARS-CoV) devotes a
      significant portion of its genome to producing nonstructural proteins required
      for viral replication. SARS-CoV nonstructural protein 9 (nsp9) was identified as
      an essential protein with RNA/DNA-binding activity, and yet its biological
      function within the replication complex remains unknown. Nsp9 forms a dimer
      through the interaction of parallel alpha-helices containing the protein-protein
      interaction motif GXXXG. In order to study the role of the nsp9 dimer in viral
      reproduction, residues G100 and G104 at the helix interface were targeted for
      mutation. Multi-angle light scattering measurements indicated that G100E, G104E,
      and G104V mutants are monomeric in solution, thereby disrupting the dimer.
      However, electrophoretic mobility assays revealed that the mutants bound RNA with
      similar affinity. Further experiments using fluorescence anisotropy showed a 10
      fold reduction in RNA binding in the G100E and G104E mutants, whereas the G104V
      mutant had only a 4-fold reduction. The structure of G104E nsp9 was determined to
      2.6-A resolution, revealing significant changes at the dimer interface. The nsp9
      mutations were introduced into SARS-CoV using a reverse genetics approach, and
      the G100E and G104E mutations were found to be lethal to the virus. The G104V
      mutant produced highly debilitated virus and eventually reverted back to the wild
      type protein sequence through a codon transversion. Together, these data indicate
      that dimerization of SARS-CoV nsp9 at the GXXXG motif is not critical for RNA
      binding but is necessary for viral replication.

PMID- 19153233
TI  - Expression of murine APOBEC3 alleles in different mouse strains and their effect
      on mouse mammary tumor virus infection.
AB  - Recent work has shown that mouse APOBEC3 restricts infection by mouse mammary
      tumor virus (MMTV) and murine leukemia virus (MLV) and that there are polymorphic
      APOBEC3 alleles found in different inbred mouse strains. For example, C57BL/6
      mice, which are resistant to Friend MLV (F-MLV), encode a APOBEC3 gene different
      from that encoded by F-MLV-susceptible BALB/c mice; the predominant RNA produced
      in C57BL/6 mice lacks exon 5 (mA3(-5)) and encodes a protein with 15 polymorphic
      amino acids. It has also been reported that BALB/c mice produce only a variant
      RNA that lacks exon 2 (mA3(-2)). In this study, we examined the effect of these
      polymorphic APOBEC3 proteins on MMTV infection. We found that the major RNA made
      in C57BL/6 and B10.BR mice lacks exon 5 but that BALB/c and C3H/HeN mice
      predominantly express an RNA that contains all nine exons. In addition to
      producing the splice variant, C57BL/6 and B10.BR cells and tissues had levels of
      mA3 RNA fivefold higher than those from BALB/c and C3H/HeN mice. A cloned C57BL/6
      derived mA3 protein lacking exon 5 inhibited MMTV infection better than a cloned
      full-length protein derived from 129/Ola RNA when packaged into MMTV virions. We
      also tested dendritic cells derived from different inbred mouse strains for their
      abilities to be infected by MMTV and showed that susceptibility to infection
      correlated with the presence of the exon 5-encoding allele. In vivo
      susceptibility to infection cosegregated with the inherited mA3 allele in a
      C57BL/6 x BALB/c backcross analysis. Moreover, virus produced in vivo in the
      mammary tissue of mA3 knockout and BALB/c mice was more infectious than that
      produced in the tissue of C57BL/6 mice. These data indicate that mA3 plays a role
      in the genetics of susceptibility and resistance to MMTV infection.

PMID- 19153234
TI  - HR-2 mutations in human immunodeficiency virus type 1 gp41 restore fusion
      kinetics delayed by HR-1 mutations that cause clinical resistance to enfuvirtide.
AB  - Enfuvirtide (ENF) prevents the entry of human immunodeficiency virus type 1 (HIV
      1) into cells by binding to the HR-1 region of the viral envelope (Env) protein
      gp41 subunit. Resistance to ENF arises via mutations in the drug binding site in
      HR-1. In addition, HR-2 mutations are commonly observed in ENF-resistant Env
      proteins, though their role remains unclear. We explored the mechanistic basis
      for clinical resistance to ENF and the role of HR-2 mutations. Using panels of
      ENF resistance-associated mutants for two patients, we found that mutations in HR
      1 slowed the fusion kinetics and that mutations in HR-2 restored fusion rates. We
      assessed the differences in the rates of fusion of these mutants from a
      temperature-arrested state and observed similar trends, suggesting that the step
      of delay occurs after coreceptor engagement. Sensitivity to neutralizing
      antibodies was unchanged by the HR-1 and HR-2 mutants in each panel. Since this
      result was in contrast to those of a previous in vitro analysis where enhanced
      sensitivity to neutralization was demonstrated for heterologous Envs with ENF
      resistance-associated HR-1 changes, we examined the context dependence of HR-1
      and HR-2 mutations by transferring the mutations seen in one patient into the Env
      context of another. These studies revealed that some, but not all, HR-1
      mutations, when placed out of context (i.e., in a patient Env where they did not
      originally arise), enhance sensitivity to neutralizing antibodies. However, in
      most cases, HR-1 mutations in ENF-treated patients evolve in a manner that
      preserves pretreatment neutralization sensitivity so as to evade the pressures of
      the immune system.

PMID- 19153235
TI  - Biochemical, biophysical, and mutational analyses of subunit interactions of the
      human cytomegalovirus nuclear egress complex.
AB  - Nuclear egress, the trafficking of herpesvirus nucleocapsids from the nucleus to
      the cytoplasm, involves two conserved viral proteins that form a complex at the
      nuclear envelope, referred to as the nuclear egress complex. In human
      cytomegalovirus, these two proteins are called UL50 and UL53. To study UL50 and
      UL53 in molecular detail, these proteins were expressed in bacteria and purified.
      To obtain highly expressed, pure proteins, it was necessary to truncate both
      constructs based on sequence conservation and predicted secondary structural
      elements. Size exclusion chromatography and analytical ultracentrifugation
      studies indicated that the truncated form of UL50 is a monomer in solution, that
      the truncated form of UL53 is a homodimer, and that, when mixed, the two proteins
      form a heterodimer. To identify residues of UL53 crucial for homodimerization and
      for heterodimerization with UL50, we constructed and expressed mutant forms of
      UL53 containing alanine substitutions in a predicted helix. Isothermal titration
      calorimetry was used to measure the binding affinities of the UL53 mutants to
      UL50. UL53 residues, the replacement of which reduced binding to UL50, form a
      surface on one face of the predicted helix. Moreover, most of the substitutions
      that reduce UL53-UL50 interactions also reduced homodimerization. Substitutions
      that reduced the interaction between UL50 and UL53 in vitro also reduced
      colocalization of full-length UL50 and UL53 at the nuclear rim in transfected
      cells. These results demonstrate direct protein-protein interactions between
      these proteins that are likely to be mediated by a helix, and they have
      implications for understanding nuclear egress and for drug discovery.

PMID- 19153236
TI  - Macrophages in vaginal but not intestinal mucosa are monocyte-like and permissive
      to human immunodeficiency virus type 1 infection.
AB  - Mucosal surfaces play a major role in human immunodeficiency virus type 1 (HIV-1)
      transmission and pathogenesis, and yet the role of lamina propria macrophages in
      mucosal HIV-1 infection has received little investigative attention. We report
      here that vaginal and intestinal macrophages display distinct phenotype and HIV-1
      permissiveness profiles. Vaginal macrophages expressed the innate response
      receptors CD14, CD89, CD16, CD32, and CD64 and the HIV-1 receptor/coreceptors
      CD4, CCR5, and CXCR4, similar to monocytes. Consistent with this phenotype, green
      fluorescent protein-tagged R5 HIV-1 entered macrophages in explanted vaginal
      mucosa as early as 30 min after inoculation of virus onto the epithelium, and
      purified vaginal macrophages supported substantial levels of HIV-1 replication by
      a panel of highly macrophage-tropic R5 viruses. In sharp contrast, intestinal
      macrophages expressed no detectable, or very low levels of, innate response
      receptors and HIV-1 receptor/coreceptors and did not support HIV-1 replication,
      although virus occasionally entered macrophages in intestinal tissue explants.
      Thus, vaginal, but not intestinal, macrophages are monocyte-like and permissive
      to R5 HIV-1 after the virus has translocated across the epithelium. These
      findings suggest that genital and gut macrophages have different roles in mucosal
      HIV-1 pathogenesis and that vaginal macrophages play a previously
      underappreciated but potentially important role in mucosal HIV-1 infection in the
      female genital tract.

PMID- 19153237
TI  - Blocking interhost transmission of influenza virus by vaccination in the guinea
      pig model.
AB  - Interventions aimed at preventing viral spread have the potential to effectively
      control influenza virus in all age groups, thereby reducing the burden of
      influenza illness. For this reason, we have examined the efficacy of vaccination
      in blocking the transmission of influenza viruses between guinea pigs. Three
      modes of immunization were compared: (i) natural infection; (ii) intramuscular
      administration of whole, inactivated influenza virus in 2 doses; and (iii)
      intranasal inoculation with live attenuated influenza virus in 2 doses. The
      ability of each immunization method to block the spread of a homologous
      (A/Panama/2007/99) H3N2 subtype and a heterologous (A/Wisconsin/67/05) H3N2
      subtype influenza virus was tested. We found that previous infection through a
      natural route provided sterilizing immunity against both homologous and
      heterologous challenges; thus, no transmission to or from previously infected
      animals was observed. Vaccination with an inactivated influenza virus vaccine, in
      contrast, did not prevent guinea pigs from becoming infected upon challenge with
      either virus. Thus, both intranasal inoculation and exposure to an acutely
      infected guinea pig led to the infection of vaccinated animals. Vaccination with
      inactivated virus did, however, reduce viral load upon challenge and decrease the
      number of secondary transmission events from vaccinated animals to naive cage
      mates. Vaccination with a live attenuated virus was found to be more efficacious
      than vaccination with inactivated virus, resulting in sterilizing immunity
      against homologous challenge and full protection against the transmission of the
      homologous and heterologous viruses to naive contacts. In conclusion, we have
      shown that the guinea pig model can be used to test influenza virus vaccines and
      that the efficiency of transmission is a valuable readout when vaccine efficacy
      is evaluated.

PMID- 19153238
TI  - Induction of APOBEC3 in vivo causes increased restriction of retrovirus
      infection.
AB  - APOBEC3 proteins are important cellular factors that restrict infection by a
      number of viruses, including human immunodeficiency virus type 1 (HIV-1).
      Previously, we found that the mouse APOBEC3 (mA3) restricts infection by mouse
      mammary tumor virus (MMTV) in its natural host. Dendritic cells (DCs) are the
      first in vivo targets of MMTV infection. In this study, we demonstrate that mA3
      expressed in target cells restricts MMTV infection in DCs ex vivo and in vivo. By
      comparing infection of DCs from mA3(+/+) and mA3(-/-) mice with one-hit viruses,
      we show that mA3 expression in target cells blocked MMTV infection at a postentry
      step and acted together with virion-packaged mA3 to inhibit infection. Similar
      results were obtained upon infection of mouse DCs with HIV-1 cores pseudotyped
      with vesicular stomatitis virus G protein. In addition, treatment of cells or
      mice with lipopolysaccharide (LPS) caused increased levels of mA3 expression and
      rendered them resistant to MMTV infection. Alpha interferon treatment had a
      similar effect. This LPS-induced resistance to infection was seen only in
      mA3(+/+) mice and not in mA3(-/-) mice, arguing that mA3 is the major anti-MMTV
      restriction factor that is induced upon DC maturation. Thus, increasing the
      levels of this intrinsic antiretroviral factor in vivo can lead to increased
      levels of restriction because of higher levels of both cell-intrinsic as well as
      virion-packaged APOBEC3.

PMID- 19153239
TI  - The NS4A protein of hepatitis C virus promotes RNA-coupled ATP hydrolysis by the
      NS3 helicase.
AB  - Nonstructural protein 3 (NS3) is an essential replicative component of the
      hepatitis C virus (HCV) and a member of the DExH/D-box family of proteins. The C
      terminal region of NS3 (NS3hel) exhibits RNA-stimulated NTPase and helicase
      activity, while the N-terminal serine protease domain of NS3 enhances RNA binding
      and unwinding by NS3hel. The nonstructural protein 4A (NS4A) binds to the NS3
      protease domain and serves as an obligate cofactor for NS3 serine protease
      activity. Given its role in stimulating protease activity, we sought to determine
      whether NS4A also influences the activity of NS3hel. Here we show that NS4A
      enhances the ability of NS3hel to bind RNA in the presence of ATP, thereby acting
      as a cofactor for helicase activity. This effect is mediated by amino acids in
      the C-terminal acidic domain of NS4A. When these residues are mutated, one
      observes drastic reductions in ATP-coupled RNA binding and duplex unwinding by
      NS3. These same mutations are lethal in HCV replicons, thereby establishing in
      vitro and in vivo that NS4A plays an important role in the helicase mechanism of
      NS3 and its function in replication.

PMID- 19153240
TI  - Biarsenical labeling of vesicular stomatitis virus encoding tetracysteine-tagged
      m protein allows dynamic imaging of m protein and virus uncoating in infected
      cells.
AB  - A recombinant vesicular stomatitis virus (VSV-PeGFP-M-MmRFP) encoding enhanced
      green fluorescent protein fused in frame with P (PeGFP) in place of P and a
      fusion matrix protein (monomeric red fluorescent protein fused in frame at the
      carboxy terminus of M [MmRFP]) at the G-L gene junction, in addition to wild-type
      (wt) M protein in its normal location, was recovered, but the MmRFP was not
      incorporated into the virions. Subsequently, we generated recombinant viruses
      (VSV-PeGFP-DeltaM-Mtc and VSV-DeltaM-Mtc) encoding M protein with a carboxy
      terminal tetracysteine tag (Mtc) in place of the M protein. These recombinant
      viruses incorporated Mtc at levels similar to M in wt VSV, demonstrating recovery
      of infectious rhabdoviruses encoding and incorporating a tagged M protein.
      Virions released from cells infected with VSV-PeGFP-DeltaM-Mtc and labeled with
      the biarsenical red dye (ReAsH) were dually fluorescent, fluorescing green due to
      incorporation of PeGFP in the nucleocapsids and red due to incorporation of ReAsH
      labeled Mtc in the viral envelope. Transport and subsequent association of M
      protein with the plasma membrane were shown to be independent of microtubules.
      Sequential labeling of VSV-DeltaM-Mtc-infected cells with the biarsenical dyes
      ReAsH and FlAsH (green) revealed that newly synthesized M protein reaches the
      plasma membrane in less than 30 min and continues to accumulate there for up to 2
      1/2 hours. Using dually fluorescent VSV, we determined that following adsorption
      at the plasma membrane, the time taken by one-half of the virus particles to
      enter cells and to uncoat their nucleocapsids in the cytoplasm is approximately
      28 min.

PMID- 19153241
TI  - An invariant surface patch on the TRIM5alpha PRYSPRY domain is required for
      retroviral restriction but dispensable for capsid binding.
AB  - TRIM5alpha is a retrovirus restriction factor in the host cell cytoplasm that
      blocks infection before provirus establishment. Restriction activity requires
      capsid (CA)-specific recognition by the PRYSPRY domain of TRIM5alpha. To better
      understand the restriction mechanism, nine charge-cluster-to-triple-alanine
      mutants in the TRIM5alpha PRYSPRY domain were assessed for CA-specific
      restriction activity. Five mutants distributed along the TRIM5alpha PRYSPRY
      primary sequence disrupted restriction activity against N-tropic murine leukemia
      virus and equine infectious anemia virus. Modeling of the TRIM5alpha PRYSPRY
      domain based on the crystal structures of PRYSPRY-19q13.4.1, GUSTAVUS, and TRIM21
      identified a surface patch where disruptive mutants clustered. All mutants in
      this patch retained CA-binding activity, a reticular distribution in the
      cytoplasm, and steady-state protein levels comparable to those of the wild type.
      Residues in the essential patch are conserved in TRIM5alpha orthologues and in
      closely related paralogues. The same surface patch in the TRIM18 and TRIM20
      PRYSPRY domains is the site of mutants causing Opitz syndrome and familial
      Mediterranean fever. These results indicate that, in addition to CA-specific
      binding, the PRYSPRY domain possesses a second function, possibly binding of a
      cofactor, that is essential for retroviral restriction activity by TRIM5alpha.

PMID- 19153242
TI  - A key role for heat shock protein 70 in the localization and insertion of
      tombusvirus replication proteins to intracellular membranes.
AB  - Plus-stranded RNA viruses coopt host proteins to promote their robust replication
      in infected hosts. Tomato bushy stunt tombusvirus (TBSV) is a model virus that
      can replicate a small replicon RNA in Saccharomyces cerevisiae and in plants. The
      tombusvirus replicase complex contains heat shock protein 70 (Hsp70), an abundant
      cytosolic chaperone, which is required for TBSV replication. To dissect the
      function of Hsp70 in TBSV replication, in this paper we use an Hsp70 mutant (ssa1
      ssa2) yeast strain that supports a low level of TBSV replication. Using confocal
      laser microscopy and cellular fractionation experiments, we find that the
      localization of the viral replication proteins changes to the cytosol in the
      mutant cells from the peroxisomal membranes in wild-type cells. An in vitro
      membrane insertion assay shows that Hsp70 promotes the integration of the viral
      replication proteins into subcellular membranes. This step seems to be critical
      for the assembly of the viral replicase complex. Using a gene-silencing approach
      and quercetin as a chemical inhibitor to downregulate Hsp70 levels, we also
      confirm the significance of cytosolic Hsp70 in the replication of TBSV and other
      plant viruses in a plant host. Taken together, our results suggest that cytosolic
      Hsp70 plays multiple roles in TBSV replication, such as affecting the subcellular
      localization and membrane insertion of the viral replication proteins as well as
      the assembly of the viral replicase.

PMID- 19153243
TI  - Differential roles of migratory and resident DCs in T cell priming after mucosal
      or skin HSV-1 infection.
AB  - Although mucosal surfaces represent the main portal of entry for pathogens, the
      mechanism of antigen presentation by dendritic cells (DCs) that patrol various
      mucosal tissues remains unclear. Instead, much effort has focused on the
      understanding of initiation of immune responses generated against antigens
      delivered by injection. We examined the contributions of migratory versus lymph
      node-resident DC populations in antigen presentation to CD4 and CD8 T cells after
      needle injection, epicutaneous infection, or vaginal mucosal herpes simplex virus
      (HSV) 1 infection. We show that upon needle injection, HSV-1 became lymph-borne
      and was rapidly presented by lymph node-resident DCs to CD4 and CD8 T cells. In
      contrast, after vaginal HSV-1 infection, antigens were largely presented by
      tissue-derived migrant DCs with delayed kinetics. In addition, migrant DCs made
      more frequent contact with HSV-specific T cells after vaginal infection compared
      with epicutaneous infection. Thus, both migrant and resident DCs play an
      important role in priming CD8 and CD4 T cell responses, and their relative
      importance depends on the mode of infection in vivo.

PMID- 19153244
TI  - Host ER-parasitophorous vacuole interaction provides a route of entry for antigen
      cross-presentation in Toxoplasma gondii-infected dendritic cells.
AB  - Toxoplasma gondii tachyzoites infect host cells by an active invasion process
      leading to the formation of a specialized compartment, the parasitophorous
      vacuole (PV). PVs resist fusion with host cell endosomes and lysosomes and are
      thus distinct from phagosomes. Because the parasite remains sequestered within
      the PV, it is unclear how T. gondii-derived antigens (Ag's) access the major
      histocompatibility complex (MHC) class I pathway for presentation to CD8(+) T
      cells. We demonstrate that recruitment of host endoplasmic reticulum (hER) to the
      PV in T. gondii-infected dendritic cells (DCs) directly correlates with cross
      priming of CD8(+) T cells. Furthermore, we document by immunoelectron microscopy
      the transfer of hER components into the PV, a process indicative of direct fusion
      between the two compartments. In strong contrast, no association between hER and
      phagosomes or Ag presentation activity was observed in DCs containing
      phagocytosed live or dead parasites. Importantly, cross-presentation of parasite
      derived Ag in actively infected cells was blocked when hER retrotranslocation was
      inhibited, indicating that the hER serves as a conduit for the transport of Ag
      between the PV and host cytosol. Collectively, these findings demonstrate that
      pathogen-driven hER-PV interaction can serve as an important mechanism for Ag
      entry into the MHC class I pathway and CD8(+) T cell cross-priming.

PMID- 19153250
TI  - Jeremy Farrar: When disaster strikes. Interview by Amy Maxmen.
AB  - Jeremy Farrar had not intended to be at the forefront of avian influenza
      research. But as the director of the Oxford University Clinical Research Unit in
      Ho Chi Minh City, the bird flu outbreak found him.

PMID- 19153251
TI  - On the trail of disease in Southeast Asia.

PMID- 19153252
TI  - Characterization of antennal trichoid sensilla from female southern house
      mosquito, Culex quinquefasciatus Say.
AB  - Culex quinquefasciatus, the southern house mosquito, is highly dependent on its
      olfactory system for vector-related activities such as host seeking and
      oviposition. The antennae are the primary olfactory organs in mosquitoes. We
      describe 5 morphological types of sensilla on the antenna of C. quinquefasciatus:
      1) a pair of sensilla coeloconica located at the distal tip, 2) long and short
      sensilla chaetica present on all 13 antennal flagella, 3) sensilla ampullacea
      found on the 2 proximal-most flagella, 4) 2 morphological types of grooved pegs
      dispersed throughout the flagella, and 5) 5 morphological subtypes of sensilla
      trichodea distributed among all flagella. Antennal trichoid and grooved peg
      sensilla of mosquitoes have been demonstrated to house the olfactory receptor
      neurons (ORNs) that detect many of the odors involved in eliciting vector-related
      behaviors. In order to initiate the functional characterization of the peripheral
      olfactory system in female C. quinquefasciatus, we mapped the physiological
      responses of all 5 morphological subtypes of sensilla trichodea to an odor panel
      of 44 behaviorally relevant odor compounds. We identified 17 functional classes
      of sensilla trichodea: 3 short sharp-tipped, 9 short blunt-tipped type I, and 5
      short blunt-tipped type II sensilla. One morphological subtype remains
      unclassified as the long sharp-tipped sensilla did not respond to any of the
      volatiles tested. The functional classes of the ORNs were analyzed with respect
      to stimulus response profiles, stimuli sensitivity, and temporal coding patterns.
      Comparisons with other functionally classified mosquito antennal sensilla
      trichodea are discussed.

PMID- 19153253
TI  - The strength of selection against the yeast prion [PSI+].
AB  - The [PSI(+)] prion causes widespread readthrough translation and is rare in
      natural populations of Saccharomyces, despite the fact that sex is expected to
      cause it to spread. Using the recently estimated rate of Saccharomyces
      outcrossing, we calculate the strength of selection necessary to maintain
      [PSI(+)] at levels low enough to be compatible with data. Using the best
      available parameter estimates, we find selection against [PSI(+)] to be
      significant. Inference regarding selection on modifiers of [PSI(+)] appearance
      depends on obtaining more precise and accurate estimates of the product of yeast
      effective population size N(e) and the spontaneous rate of [PSI(+)] appearance m.
      The ability to form [PSI(+)] has persisted in yeast over a long period of
      evolutionary time, despite a diversity of modifiers that could abolish it. If
      mN(e) < 1, this may be explained by insufficiently strong selection. If mN(e) >
      1, then selection should favor the spread of [PSI(+)] resistance modifiers. In
      this case, rare conditions where [PSI(+)] is adaptive may permit its persistence
      in the face of negative selection.

PMID- 19153254
TI  - Reduced fertility of Drosophila melanogaster hybrid male rescue (Hmr) mutant
      females is partially complemented by Hmr orthologs from sibling species.
AB  - The gene Hybrid male rescue (Hmr) causes lethality in interspecific hybrids
      between Drosophila melanogaster and its sibling species. Hmr has functionally
      diverged for this interspecific phenotype because lethality is caused
      specifically by D. melanogaster Hmr but not by D. simulans or D. mauritiana Hmr.
      Hmr was identified by the D. melanogaster partial loss-of-function allele Hmr1,
      which suppresses hybrid lethality but has no apparent phenotype within pure
      species D. melanogaster. Here we have investigated the possible function of Hmr
      in D. melanogaster females using stronger mutant alleles. Females homozygous for
      Hmr mutants have reduced viability posteclosion and significantly reduced
      fertility. We find that reduced fertility of Hmr mutants is caused by a reduction
      in the number of eggs laid as well as reduced zygotic viability. Cytological
      analysis reveals that ovarioles from Hmr mutant females express markers that
      distinguish various stages of wild-type oogenesis, but that developing egg
      chambers fail to migrate posteriorly. D. simulans and D. mauritiana Hmr+
      partially complement the reduced fertility of a D. melanogaster Hmr mutation.
      This partial complementation contrasts with the complete functional divergence
      previously observed for the interspecific hybrid lethality phenotype. We also
      investigate here the molecular basis of hybrid rescue associated with a second D.
      melanogaster hybrid rescue allele, In(1)AB. We show that In(1)AB is mutant for
      Hmr function, likely due to a missense mutation in an evolutionarily conserved
      amino acid. Two independently discovered hybrid rescue mutations are therefore
      allelic.

PMID- 19153255
TI  - Rice Pi5-mediated resistance to Magnaporthe oryzae requires the presence of two
      coiled-coil-nucleotide-binding-leucine-rich repeat genes.
AB  - Rice blast, caused by the fungus Magnaporthe oryzae, is one of the most
      devastating diseases of rice. To understand the molecular basis of Pi5-mediated
      resistance to M. oryzae, we cloned the resistance (R) gene at this locus using a
      map-based cloning strategy. Genetic and phenotypic analyses of 2014 F2 progeny
      from a mapping population derived from a cross between IR50, a susceptible rice
      cultivar, and the RIL260 line carrying Pi5 enabled us to narrow down the Pi5
      locus to a 130-kb interval. Sequence analysis of this genomic region identified
      two candidate genes, Pi5-1 and Pi5-2, which encode proteins carrying three motifs
      characteristic of R genes: an N-terminal coiled-coil (CC) motif, a nucleotide
      binding (NB) domain, and a leucine-rich repeat (LRR) motif. In genetic
      transformation experiments of a susceptible rice cultivar, neither the Pi5-1 nor
      the Pi5-2 gene was found to confer resistance to M. oryzae. In contrast,
      transgenic rice plants expressing both of these genes, generated by crossing
      transgenic lines carrying each gene individually, conferred Pi5-mediated
      resistance to M. oryzae. Gene expression analysis revealed that Pi5-1 transcripts
      accumulate after pathogen challenge, whereas the Pi5-2 gene is constitutively
      expressed. These results indicate that the presence of these two genes is
      required for rice Pi5-mediated resistance to M. oryzae.

PMID- 19153256
TI  - A new family of Ty1-copia-like retrotransposons originated in the tomato genome
      by a recent horizontal transfer event.
AB  - Rider is a novel and recently active Ty1-copia-like retrotransposon isolated from
      the T3238fer mutant of tomato. Structurally, it is delimited by a duplication of
      target sites and contains two long terminal direct repeats and an internal open
      reading frame, which encodes a Ty1-copia-type polyprotein with characteristic
      protein domains required for retrotransposition. The family of Rider elements has
      an intermediate copy number and is scattered in the chromosomes of tomato. Rider
      family members in the tomato genome share high sequence similarity, but different
      structural groups were identified (full-size elements, deletion derivatives, and
      solo LTRs). Southern blot analysis in Solanaceae species showed that Rider was a
      Lycopersicon-specific element. Sequence analysis revealed that among other
      plants, two Arabidopsis elements (named as Rider-like 1 and Rider-like 2) are
      most similar to Rider in both the coding and noncoding regions. RT-PCR analysis
      indicates that Rider is constitutively expressed in tomato plants. The phylogeny
      based parsimony analysis and the sequence substitution analyses of these data
      suggest that these Rider-like elements originated from a recent introgression of
      Rider into the tomato genome by horizontal transfer 1-6 million years ago.
      Considering its transcriptional activity and the recent insertion of the element
      into at least two genes, Rider is a recently active retrotransposon in the tomato
      genome.

PMID- 19153257
TI  - Comparative analysis of Pdf-mediated circadian behaviors between Drosophila
      melanogaster and D. virilis.
AB  - A group of small ventrolateral neurons (s-LN(v)'s) are the principal pacemaker
      for circadian locomotor rhythmicity of Drosophila melanogaster, and the pigment
      dispersing factor (Pdf) neuropeptide plays an essential role as a clock messenger
      within these neurons. In our comparative studies on Pdf-associated circadian
      rhythms, we found that daily locomotor activity patterns of D. virilis were
      significantly different from those of D. melanogaster. Activities of D. virilis
      adults were mainly restricted to the photophase under light:dark cycles and
      subsequently became arrhythmic or weakly rhythmic in constant conditions. Such
      activity patterns resemble those of Pdf(01) mutant of D. melanogaster.
      Intriguingly, endogenous D. virilis Pdf (DvPdf) expression was not detected in
      the s-LN(v)-like neurons in the adult brains, implying that the Pdf(01)-like
      behavioral phenotypes of D. virilis are attributed in part to the lack of DvPdf
      in the s-LN(v)-like neurons. Heterologous transgenic analysis showed that cis
      regulatory elements of the DvPdf transgene are capable of directing their
      expression in all endogenous Pdf neurons including s-LN(v)'s, as well as in non
      Pdf clock neurons (LN(d)'s and fifth s-LN(v)) in a D. melanogaster host. Together
      these findings suggest a significant difference in the regulatory mechanisms of
      Pdf transcription between the two species and such a difference is causally
      associated with species-specific establishment of daily locomotor activity
      patterns.

PMID- 19153258
TI  - The interaction of knotted1 and thick tassel dwarf1 in vegetative and
      reproductive meristems of maize.
AB  - In Arabidopsis, SHOOT MERISTEMLESS (STM) and CLAVATA1 (CLV1) competitively
      regulate meristem homeostasis. Here, we explore the interaction of their maize
      homologs knotted1 (kn1) and thick tassel dwarf1 (td1). kn1 mutants form fewer
      lateral organs and td1 inflorescences are fasciated with additional floral
      organs. Double mutants show kn1 epistatic to td1 in seedling and ear development
      but dose-sensitivity exists later to promote leaf initiation. Thus kn1 and td1
      function in a pathway to maintain meristem homeostasis but their products may
      interact with different partners during development.

PMID- 19153260
TI  - Selective genotyping and phenotyping strategies in a complex trait context.
AB  - Selective genotyping and phenotyping strategies are used to lower the cost of
      quantitative trait locus studies. Their efficiency has been studied primarily in
      simplified contexts--when a single locus contributes to the phenotype, and when
      the residual error (phenotype conditional on the genotype) is normally
      distributed. It is unclear how these strategies will perform in the context of
      complex traits where multiple loci, possibly linked or epistatic, may contribute
      to the trait. We also do not know what genotyping strategies should be used for
      nonnormally distributed phenotypes. For time-to-event phenotypes there is the
      additional question of choosing follow-up time duration. We use an information
      perspective to examine these experimental design issues in the broader context of
      complex traits and make recommendations on their use.

PMID- 19153261
TI  - The fixation probability of rare mutators in finite asexual populations.
AB  - A mutator is an allele that increases the mutation rate throughout the genome by
      disrupting some aspect of DNA replication or repair. Mutators that increase the
      mutation rate by the order of 100-fold have been observed to spontaneously emerge
      and achieve high frequencies in natural populations and in long-term laboratory
      evolution experiments with Escherichia coli. In principle, the fixation of
      mutator alleles is limited by (i) competition with mutations in wild-type
      backgrounds, (ii) additional deleterious mutational load, and (iii) random
      genetic drift. Using a multiple-locus model and employing both simulation and
      analytic methods, we investigate the effects of these three factors on the
      fixation probability Pfix of an initially rare mutator as a function of
      population size N, beneficial and deleterious mutation rates, and the strength of
      mutations s. Our diffusion-based approximation for Pfix successfully captures
      effects ii and iii when selection is fast compared to mutation (micro/s<<1). This
      enables us to predict the conditions under which mutators will be evolutionarily
      favored. Surprisingly, our simulations show that effect i is typically small for
      strong-effect mutators. Our results agree semiquantitatively with existing
      laboratory evolution experiments and suggest future experimental directions.

PMID- 19153262
TI  - Assessing blood pressure control in dialysis patients: finally a step forward.

PMID- 19153263
TI  - Dry-weight reduction in hypertensive hemodialysis patients (DRIP): a randomized,
      controlled trial.
AB  - Volume excess is thought to be important in the pathogenesis of hypertension
      among hemodialysis patients. To determine whether additional volume reduction
      will result in improvement in blood pressure (BP) among hypertensive patients on
      hemodialysis and to evaluate the time course of this response, we randomly
      assigned long-term hypertensive hemodialysis patients to ultrafiltration or
      control groups. The additional ultrafiltration group (n=100) had the dry weight
      probed without increasing time or duration of dialysis, whereas the control group
      (n=50) only had physician visits. The primary outcome was change in systolic
      interdialytic ambulatory BP. Postdialysis weight was reduced by 0.9 kg at 4 weeks
      and resulted in -6.9 mm Hg (95% CI: -12.4 to -1.3 mm Hg; P=0.016) change in
      systolic BP and -3.1 mm Hg (95% CI: -6.2 to -0.02 mm Hg; P=0.048) change in
      diastolic BP. At 8 weeks, dry weight was reduced 1 kg, systolic BP changed -6.6
      mm Hg (95% CI: -12.2 to -1.0 mm Hg; P=0.021), and diastolic BP changed -3.3 mm Hg
      (95% CI: -6.4 to -0.2 mm Hg; P=0.037) from baseline. The Mantel-Hanzel combined
      odds ratio for systolic BP reduction of > or =10 mm Hg was 2.24 (95% CI: 1.32 to
      3.81; P=0.003). There was no deterioration seen in any domain of the kidney
      disease quality of life health survey despite an increase in intradialytic signs
      and symptoms of hypotension. The reduction of dry weight is a simple,
      efficacious, and well-tolerated maneuver to improve BP control in hypertensive
      hemodialysis patients. Long-term control of BP will depend on continued
      assessment and maintenance of dry weight.

PMID- 19153259
TI  - Historical divergence and gene flow in the genus Zea.
AB  - Gene flow plays a fundamental role in plant evolutionary history, yet its role in
      population divergence--and ultimately speciation--remains poorly understood. We
      investigated gene flow and the modalities of divergence in the domesticated Zea
      mays ssp. mays and three wild Zea taxa using sequence polymorphism data from 26
      nuclear loci. We described diversity across loci and assessed evidence for
      adaptive and purifying selection at nonsynonymous sites. For each of three
      divergence events in the history of these taxa, we used approximate Bayesian
      simulation to estimate population sizes and divergence times and explicitly
      compare among alternative models of divergence. Our estimates of divergence times
      are surprisingly consistent with previous data from other markers and suggest
      rapid diversification of lineages within Zea in the last approximately 150,000
      years. We found widespread evidence of historical gene flow, including evidence
      for divergence in the face of gene flow. We speculate that cultivated maize may
      serve as a bridge for gene flow among otherwise allopatric wild taxa.

PMID- 19153264
TI  - Dietary salt intake, salt sensitivity, and cardiovascular health.

PMID- 19153265
TI  - Effect of the direct Renin inhibitor aliskiren, the Angiotensin receptor blocker
      losartan, or both on left ventricular mass in patients with hypertension and left
      ventricular hypertrophy.
AB  - BACKGROUND: Left ventricular (LV) hypertrophy, a marker of cardiac end-organ
      damage, is associated with an increased risk of cardiovascular morbidity and
      mortality. Inhibitors of the renin-angiotensin-aldosterone system may reduce LV
      mass to a greater extent than other antihypertensive agents. We compared the
      effect of aliskiren, the first orally active direct renin inhibitor, the
      angiotensin-receptor blocker losartan, and their combination on the reduction of
      LV mass in hypertensive patients. METHODS AND RESULTS: We randomized 465 patients
      with hypertension, increased ventricular wall thickness, and body mass index >25
      kg/m(2) to receive aliskiren 300 mg, losartan 100 mg, or their combination daily
      for 9 months. Patients were treated to standard blood pressure targets with add
      on therapy, excluding other inhibitors of the renin-angiotensin-aldosterone
      system and beta-blockers. Patients underwent cardiovascular magnetic resonance
      imaging for assessment of LV mass at baseline and at study completion. The
      primary objective was to compare change in LV mass index from baseline to follow
      up in the combination and losartan arms; the secondary objective was to determine
      whether aliskiren was noninferior to losartan in reducing LV mass index from
      baseline to follow-up. Systolic and diastolic blood pressures were reduced
      similarly in all treatment groups (6.5+/-14.9/3.8+/-10.1 mm Hg in the aliskiren
      group; 5.5+/-15.6/3.7+/-10.7 mm Hg in the losartan group; 6.6+/-16.6/4.6+/-10.5
      mm Hg in the combination arm; P<0.0001 within groups, P=0.81 between groups). LV
      mass index was reduced significantly from baseline in all treatment groups (4.9-,
      4.8-, and 5.8 g/m(2) reductions in the aliskiren, losartan, and combination arms,
      respectively; P<0.0001 for all treatment groups). The reduction in LV mass index
      in the combination group was not significantly different from that with losartan
      alone (P=0.52). Aliskiren was as effective as losartan in reducing LV mass index
      (P<0.0001 for noninferiority). Safety and tolerability were similar across all
      treatment groups. CONCLUSIONS: Aliskiren was as effective as losartan in
      promoting LV mass regression. Reduction in LV mass with the combination of
      aliskiren plus losartan was not significantly different from that with losartan
      monotherapy, independent of blood pressure lowering. These findings suggest that
      aliskiren was as effective as an angiotensin receptor blocker in attenuating this
      measure of myocardial end-organ damage in hypertensive patients with LV
      hypertrophy.

PMID- 19153266
TI  - Deficiency of the NR4A neuron-derived orphan receptor-1 attenuates neointima
      formation after vascular injury.
AB  - BACKGROUND: The neuron-derived orphan receptor-1 (NOR1) belongs to the
      evolutionary highly conserved and most ancient NR4A subfamily of the nuclear
      hormone receptor superfamily. Members of this subfamily function as early
      response genes regulating key cellular processes, including proliferation,
      differentiation, and survival. Although NOR1 has previously been demonstrated to
      be required for smooth muscle cell proliferation in vitro, the role of this
      nuclear receptor for the proliferative response underlying neointima formation
      and target genes trans-activated by NOR1 remain to be defined. METHODS AND
      RESULTS: Using a model of guidewire-induced arterial injury, we demonstrate
      decreased neointima formation in NOR1(-/-) mice compared with wild-type mice. In
      vitro, NOR1-deficient smooth muscle cells exhibit decreased proliferation as a
      result of a G(1)-->S phase arrest of the cell cycle and increased apoptosis in
      response to serum deprivation. NOR1 deficiency alters phosphorylation of the
      retinoblastoma protein by preventing mitogen-induced cyclin D1 and D2 expression.
      Conversely, overexpression of NOR1 induces cyclin D1 expression and the
      transcriptional activity of the cyclin D1 promoter in transient reporter assays.
      Gel shift and chromatin immunoprecipitation assays identified a putative response
      element for NR4A receptors in the cyclin D1 promoter, to which NOR1 is recruited
      in response to mitogenic stimulation. Finally, we provide evidence that these
      observations are applicable in vivo by demonstrating decreased cyclin D1
      expression during neointima formation in NOR1-deficient mice. CONCLUSIONS: These
      experiments characterize cyclin D1 as an NOR1-regulated target gene in smooth
      muscle cells and demonstrate that NOR1 deficiency decreases neointima formation
      in response to vascular injury.

PMID- 19153267
TI  - Altered bone morphogenetic protein and transforming growth factor-beta signaling
      in rat models of pulmonary hypertension: potential for activin receptor-like
      kinase-5 inhibition in prevention and progression of disease.
AB  - BACKGROUND: Recent genetic studies have highlighted the role of the bone
      morphogenetic protein (BMP)/transforming growth factor (TGF)-beta signaling
      pathways in the pathogenesis of familial pulmonary arterial hypertension (PAH).
      It remains unclear whether alterations in these pathways contribute to other
      forms of pulmonary hypertension and to what extent these changes can be exploited
      for therapeutic intervention. METHODS AND RESULTS: We studied BMP/TGF-beta
      signaling in 2 rat models of PAH due to chronic hypoxia and monocrotaline. In
      both models, there was a significant reduction in lung BMP type IA receptor and
      BMP type II receptor mRNA expression, although these changes were more pronounced
      in the monocrotaline model. This was accompanied by a reduction in lung levels of
      phospho-Smad1/5 and Id (inhibitor of DNA binding) gene expression in the
      monocrotaline model. In contrast, we observed increased TGF-beta activity, again
      more marked in the monocrotaline model, as evidenced by increased phospho-Smad2/3
      and increased expression of TGF-beta-regulated genes. Immunohistochemistry
      revealed increased TGF-beta(1) expression in pulmonary artery smooth muscle cells
      and macrophages surrounding remodeled pulmonary arteries in monocrotaline rats.
      Inhibition of activin receptor-like kinase-5 signaling in vivo with the selective
      small-molecule inhibitor IN-1233 prevented PAH, right ventricular hypertrophy,
      and vascular remodeling after monocrotaline injection and inhibited the
      progression of established PAH in this model. No significant effect was observed
      in hypoxic PAH. In vitro studies confirmed that TGF-beta stimulated migration of
      distal rat pulmonary artery smooth muscle cells and that this effect was
      inhibited by IN-1233. CONCLUSIONS: Disruption of BMP/TGF-beta signaling is more
      pronounced in the monocrotaline model of PAH than in the chronic hypoxia model.
      Increased TGF-beta activity is associated with greater macrophage recruitment
      with monocrotaline treatment. Inhibition of TGF-beta signaling via activin
      receptor-like kinase-5 prevents development and progression of PAH in the
      monocrotaline model and may involve inhibition of pulmonary artery smooth muscle
      cell migration.

PMID- 19153268
TI  - Long-term trends in first hospitalization for heart failure and subsequent
      survival between 1986 and 2003: a population study of 5.1 million people.
AB  - BACKGROUND: We examined whether population-level hospitalization rates for heart
      failure (HF) and subsequent survival have continued to improve since the turn of
      the century. We also examined trends in the prescribing of evidence-based
      pharmacological treatment for HF. METHODS AND RESULTS: All patients in Scotland
      hospitalized with a first episode of HF between 1986 and 2003 were followed up
      until death or the end of 2004. Prescriptions of evidence-based treatments issued
      from 1997 to 2003 by a sample of primary care practices were also examined. A
      total of 116 556 individuals (52.6% women) had a first hospital discharge for HF.
      Age-adjusted first hospitalization rates for HF (per 100 000; 95% CI in
      parentheses) rose from 124 (119 to 129) in 1986 to 162 (157 to 168) in 1994 and
      then fell to 105 (101 to 109) in 2003 in men; in women, they rose from 128 (123
      to 132) in 1986 to 160 (155 to 165) in 1993, falling to 101 (97 to 105) in 2003.
      Case-fatality rates fell steadily over the period. Adjusted 30-day case-fatality
      rates fell after discharge (adjusted odds [2003 versus 1986] 0.59 [95% CI 0.45 to
      0.63] in men and 0.77 [95% CI 0.67 to 0.88] in women). Adjusted 1- and 5-year
      survival improved similarly. Median survival increased from 1.33 to 2.34 years in
      men and from 1.32 to 1.79 years in women. Age-adjusted prescribing rates for
      angiotensin-converting enzyme inhibitors, beta-blockers, and spironolactone
      increased from 1997 to 2003 (all P<0.0001 for trend). CONCLUSIONS: After rising
      between 1986 and 1994, rates of first hospitalization for HF declined. Case
      fatality rates also fell. Prescribing rates for HF therapies increased from 1997
      to 2003. These findings suggest that improvements in the prevention and treatment
      of HF may have had progressive, sustained effects on outcomes at the population
      level; however, prognosis remains poor in HF.

PMID- 19153270
TI  - Discordant secular trends in elevated blood pressure and obesity in children and
      adolescents in a rapidly developing country.
AB  - BACKGROUND: The effect of the increasing prevalence of obesity on blood pressure
      (BP) secular trends is unclear. We analyzed BP and body mass index secular trends
      between 1998 and 2006 in children and adolescents of the Seychelles, a rapidly
      developing island state in the African region. METHODS AND RESULTS: School-based
      surveys were conducted annually between 1998 and 2006 among all students in 4
      school grades (kindergarten and 4th, 7th, and 10th years of compulsory school).
      We used the Centers for Disease Control and Prevention criteria to define obesity
      and elevated BP. The same methods and instruments were used in all surveys. Some
      25 586 children and adolescents 4 to 18 years of age contributed 43 867
      observations. Although the prevalence of obesity in boys and girls increased from
      5.1% and 6.0%, respectively, in 1998 to 2000 to 8.0% and 8.7% in 2004 to 2006,
      the prevalence of elevated BP decreased from 8.4% and 9.8% to 6.9% and 7.8%.
      During the interval, mean age-adjusted body mass index increased by 0.57 kg/m(2)
      in boys and 0.58 kg/m(2) in girls. Mean age- and height-adjusted systolic BP
      decreased by -3.0 mm Hg in boys and -2.8 mm Hg in girls, whereas mean diastolic
      BP did not change substantially in boys (-0.2 mm Hg) and increased slightly in
      girls (0.4 mm Hg). CONCLUSIONS: At a population level, the marked increase in the
      prevalence of obesity in children and adolescents in the Seychelles was not
      associated with a commensurate secular rise in mean BP.

PMID- 19153269
TI  - Ambient air pollution exaggerates adipose inflammation and insulin resistance in
      a mouse model of diet-induced obesity.
AB  - BACKGROUND: There is a strong link between urbanization and type 2 diabetes
      mellitus. Although a multitude of mechanisms have been proposed, there are no
      studies evaluating the impact of ambient air pollutants and the propensity to
      develop type 2 diabetes mellitus. We hypothesized that exposure to ambient fine
      particulate matter (<2.5 mum; PM(2.5)) exaggerates diet-induced insulin
      resistance, adipose inflammation, and visceral adiposity. METHODS AND RESULTS:
      Male C57BL/6 mice were fed high-fat chow for 10 weeks and randomly assigned to
      concentrated ambient PM(2.5) or filtered air (n=14 per group) for 24 weeks.
      PM(2.5)-exposed C57BL/6 mice exhibited marked whole-body insulin resistance,
      systemic inflammation, and an increase in visceral adiposity. PM(2.5) exposure
      induced signaling abnormalities characteristic of insulin resistance, including
      decreased Akt and endothelial nitric oxide synthase phosphorylation in the
      endothelium and increased protein kinase C expression. These abnormalilties were
      associated with abnormalities in vascular relaxation to insulin and
      acetylcholine. PM(2.5) increased adipose tissue macrophages (F4/80(+) cells) in
      visceral fat expressing higher levels of tumor necrosis factor-alpha/interleukin
      6 and lower interleukin-10/N-acetyl-galactosamine specific lectin 1. To test the
      impact of PM(2.5) in eliciting direct monocyte infiltration into fat, we rendered
      FVBN mice expressing yellow fluorescent protein (YFP) under control of a monocyte
      specific promoter (c-fms, c-fms(YFP)) diabetic over 10 weeks and then exposed
      these mice to PM(2.5) or saline intratracheally. PM(2.5) induced YFP cell
      accumulation in visceral fat and potentiated YFP cell adhesion in the
      microcirculation. CONCLUSIONS: PM(2.5) exposure exaggerates insulin resistance
      and visceral inflammation/adiposity. These findings provide a new link between
      air pollution and type 2 diabetes mellitus.

PMID- 19153271
TI  - Long-term effects of enzyme replacement therapy on fabry cardiomyopathy: evidence
      for a better outcome with early treatment.
AB  - BACKGROUND: Enzyme replacement therapy with recombinant alpha-galactosidase A
      reduces left ventricular hypertrophy and improves regional myocardial function in
      patients with Fabry disease during short-term treatment. Whether enzyme
      replacement therapy is effective in all stages of Fabry cardiomyopathy during
      long-term follow-up is unknown. METHODS AND RESULTS: We studied 32 Fabry patients
      over a period of 3 years regarding disease progression and clinical outcome under
      enzyme replacement therapy. Regional myocardial fibrosis was assessed by magnetic
      resonance imaging late-enhancement technique. Echocardiographic myocardial mass
      was calculated with the Devereux formula, and myocardial function was quantified
      by ultrasonic strain-rate imaging. In addition, exercise capacity was measured by
      bicycle stress test. All measurements were repeated at yearly intervals. At
      baseline, 9 patients demonstrated at least 2 fibrotic left ventricular segments
      (severe myocardial fibrosis), 11 had 1 left ventricular segment affected (mild
      fibrosis), and 12 were without fibrosis. In patients without fibrosis, enzyme
      replacement therapy resulted in a significant reduction in left ventricular mass
      (238+/-42 g at baseline, 202+/-46 g at 3 years; P for trend <0.001), an
      improvement in myocardial function (systolic radial strain rate, 2.3+/-0.4 and
      2.9+/-0.6 seconds(-1), respectively; P for trend=0.045), and a higher exercise
      capacity obtained by bicycle stress exercise (106+/-14 and 122+/-26 W,
      respectively; P for trend=0.014). In contrast, patients with mild or severe
      fibrosis showed a minor reduction in left ventricular hypertrophy and no
      improvement in myocardial function or exercise capacity. CONCLUSIONS: These data
      suggest that treatment of Fabry cardiomyopathy with recombinant alpha
      galactosidase A should best be started before myocardial fibrosis has developed
      to achieve long-term improvement in myocardial morphology and function and
      exercise capacity.

PMID- 19153272
TI  - Endothelial progenitor cells restore renal function in chronic experimental
      renovascular disease.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) promote neovascularization and
      endothelial repair. Renal artery stenosis (RAS) may impair renal function by
      inducing intrarenal microvascular injury and remodeling. We investigated whether
      replenishment with EPCs would protect the renal microcirculation in chronic
      experimental renovascular disease. METHODS AND RESULTS: Single-kidney
      hemodynamics and function were assessed with the use of multidetector computed
      tomography in vivo in pigs with RAS, pigs with RAS 4 weeks after intrarenal
      infusion of autologous EPCs, and controls. Renal microvascular remodeling and
      angiogenic pathways were investigated ex vivo with the use of micro-computed
      tomography, histology, and Western blotting. EPCs increased renal expression of
      angiogenic factors, stimulated proliferation and maturation of new vessels, and
      attenuated renal microvascular remodeling and fibrosis in RAS. Furthermore, EPCs
      normalized the blunted renal microvascular and filtration function. CONCLUSIONS:
      The present study shows that a single intrarenal infusion of autologous EPCs
      preserved microvascular architecture and function and decreased microvascular
      remodeling in experimental chronic RAS. It is likely that restoration of the
      angiogenic cascade by autologous EPCs involved not only generation of new vessels
      but also acceleration of their maturation and stabilization. This contributed to
      preserving the blood supply, hemodynamics, and function of the RAS kidney,
      supporting EPCs as a promising therapeutic intervention for preserving the kidney
      in renovascular disease.

PMID- 19153273
TI  - Acute kidney injury after cardiac surgery: focus on modifiable risk factors.
AB  - BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is a major health
      issue. Lacking effective therapies, risk factor modification may offer a means of
      preventing this complication. The objective of the present study was to identify
      and determine the prognostic importance of such risk factors. METHODS AND
      RESULTS: Data from a multicenter cohort of 3500 adult patients who underwent
      cardiac surgery at 7 hospitals during 2004 were analyzed (using multivariable
      logistic regression modeling) to determine the independent relationships between
      3 thresholds of AKI (>25%, >50%, and >75% decrease in estimated glomerular
      filtration rate within 1 week of surgery or need for postoperative dialysis) with
      death rates, as well as to identify modifiable risk factors for AKI. The 3
      thresholds of AKI occurred in 24% (n=829), 7% (n=228), and 3% (n=119) of the
      cohort, respectively. All 3 thresholds were independently associated with a >4
      fold increase in the odds of death and could be predicted with several
      perioperative variables, including preoperative intra-aortic balloon pump use,
      urgent surgery, and prolonged cardiopulmonary bypass. In particular, 3
      potentially modifiable variables were also independently and strongly associated
      with AKI. These were preoperative anemia, perioperative red blood cell
      transfusions, and surgical reexploration. CONCLUSIONS: AKI after cardiac surgery
      is highly prevalent and prognostically important. Therapies aimed at mitigating
      preoperative anemia, perioperative red blood cell transfusions, and surgical
      reexploration may offer protection against this complication.

PMID- 19153275
TI  - Images in cardiovascular medicine. Three-dimensional remodeling of cardiomyocytes
      in a patient with aortic stenosis: scanning electron microscopy.

PMID- 19153274
TI  - Declining severity of myocardial infarction from 1987 to 2002: the
      Atherosclerosis Risk in Communities (ARIC) Study.
AB  - BACKGROUND: Death rates for coronary heart disease have been declining in the
      United States, but the reasons for this decline are not clear. One factor that
      could contribute to this decline is a reduction in the severity of acute
      myocardial infarction (MI). We hypothesized that for those patients hospitalized
      in the Atherosclerosis Risk in Communities (ARIC) Study with acute incident MI,
      there was a decline in MI severity from 1987 to 2002. METHODS AND RESULTS: The
      community surveillance component of the ARIC Study consisted of tracking
      residents 35 to 74 years of age with hospitalized MI or fatal coronary heart
      disease in 4 diverse communities. For incident, hospitalized MI, a probability
      sample of hospital discharges was validated and an MI classification was assigned
      according to an algorithm consisting of chest pain, ECG evidence, and cardiac
      biomarkers. Severity indicators were chosen from abstracted hospital charts
      validated as a definite or probable MI. With few exceptions, the MI severity
      indicators suggested a significant decline in the severity of MI during the
      period of 1987 to 2002. The percent of MI cases with major ECG abnormalities
      decreased as evidenced by a 1.9%/y (P=0.002) decline in the proportion of those
      with initial ST-segment elevation, a 3.9%/y (P<0.001) decline in those with
      subsequent Q-waves, and a 4.5%/y (P<0.001) decline in those with any major Q
      wave. Maximum creatine kinase and creatine kinase-MB values declined (5.2% and
      7.6%; P<0.001, P<0.001 per year, respectively), although in the later years,
      maximum troponin I values remained stable (1.1%/y decline; P=0.66). The percent
      with shock declined (5.7%/y; P<0.001), although those with congestive heart
      failure remained stable. A combined severity score, the Predicting Risk of Death
      in Cardiac Disease Tool (PREDICT) score, also declined (0.2%/y; P<0.001). Results
      for blacks paralleled those of the entire group, as did results for women.
      CONCLUSIONS: Evidence from ARIC community surveillance suggests that the severity
      of acute MI has declined among community residents hospitalized for incident MI.
      This reduction in severity may have contributed, along with other factors, to the
      decline in death rates for coronary heart disease.

PMID- 19153277
TI  - Letter by Kaplan regarding article, "Bacteremia associated with toothbrushing and
      dental extraction".

PMID- 19153276
TI  - Letter by Bocelli et al regarding article, "A novel method of expressing left
      ventricular mass relative to body size in children".

PMID- 19153279
TI  - Treating the long-QT syndrome in the era of implantable defibrillators.

PMID- 19153280
TI  - Ross procedure at the crossroads.

PMID- 19153281
TI  - Assessing cardiovascular risk: should we discard diastolic blood pressure?

PMID- 19153282
TI  - Developing hearts need their SPEG.

PMID- 19153283
TI  - Real-time 3-dimensional echocardiography: an integral component of the routine
      echocardiographic examination in adult patients?

PMID- 19153284
TI  - Framework for patient safety research and improvement.

PMID- 19153285
TI  - Images in cardiovascular medicine. Diagnosis of large-vessel vasculitis by [18F]
      fluorodeoxyglucose-positron emission tomography.

PMID- 19153286
TI  - Evolution of midface rejuvenation.
AB  - Age is the most significant factor contributing to the overall change in the
      appearance of an individual's facial features over time. This gradual process of
      structural weakening of the face begins during the third decade and continues to
      worsen during the remainder of an individual's lifetime. In this article we
      discuss how the approach to midface rejuvenation has evolved over time owing to
      our increased understanding of the aging process. In addition, we discuss
      specific techniques that we employ that have helped us achieve more natural and
      lasting results.

PMID- 19153287
TI  - The case for open forehead rejuvenation: a review of 1004 procedures.
AB  - OBJECTIVE: To review the role of open forehead procedures in upper-face
      rejuvenation. METHODS: The clinical records of consecutive patients undergoing a
      coronal or trichophytic brow-lift from July 1, 1993, to June 30, 2005, were
      reviewed. Patient demographics and complication rates were tabulated and compared
      with published rates for endoscopic brow-lifts. Patient questionnaires were sent
      to correlate subjective outcome measures with objective clinical record data. To
      obtain population-based perceptions, 200 women aged 30 to 70 years were surveyed
      at a local mall. RESULTS: A total of 628 coronal and 376 trichophytic forehead
      lifts were performed for which there were clinical records. There were 6
      revisions (0.57%), no hematomas, 12 cases of permanent numbness (1.20%), 7 cases
      of permanent alopecia (0.70%), and no cases of permanent frontal branch weakness.
      The adjusted response rate for the questionnaire was 64.0% (416 of 650).
      CONCLUSIONS: Open procedures in this series had a complication rate equal to or
      lower than published rates in endoscopic brow-lift series. Open brow-lift
      procedures are an effective means of upper-face rejuvenation and, when performed
      correctly, demonstrate high rates of patient satisfaction.

PMID- 19153288
TI  - Free cartilage grafts and healing by secondary intention: a viable reconstructive
      combination after excision of nonmelanoma skin cancer in the nasal alar region.
AB  - OBJECTIVE: To assess the feasibility and outcome of free cartilage grafts left to
      heal by secondary intention in the reconstruction of nasal alar skin defects.
      DESIGN: We describe the retrospective analysis of 13 patients who were treated in
      a single department with the use of free cartilage grafts in combination with
      secondary intention healing for reconstruction of the alar subunit and lateral
      nasal wall defects after Mohs surgery for cutaneous cancer. Outcome measures
      included patient and surgeon satisfaction, alar retraction, cartilage extrusion,
      nasal valve collapse, revision rate, and time to healing. RESULTS: All wounds
      healed uneventfully by secondary intention, and the results were gauged as at
      least satisfactory by the patient and the surgeon. In 3 patients, minor aesthetic
      faults were evident; in 1 patient, the underlying cartilage was prominent and a
      hypertrophic scar also developed; in 1 patient, there was some alar notching; and
      in 1 other patient, a hypertrophic scar developed. One patient had a functional
      complaint of nasal blockage on the side that was surgically treated. CONCLUSIONS:
      Free cartilage implants in combination with secondary intention healing is a
      relatively simple, cost-effective, 1-stage technique. Our results demonstrate
      that this alternative reconstructive method is a viable option for small and deep
      defects of the alar subunit and the nasal sidewall of the nose. The donor site
      morbidity is limited to the ear.

PMID- 19153289
TI  - Autologous fat grafting: long-term evidence of its efficacy in midfacial
      rejuvenation.
AB  - OBJECTIVE: To provide quantitative objective data demonstrating the longevity and
      amount of volume augmentation in the midface obtained with autologous fat
      grafting. METHODS: A prospective analysis of all patients who underwent
      autologous fat transfer to the midface region at our private practice and were
      followed up for at least 1 year. Three-dimensional imaging was performed with a
      Canfield Scientific Vectra camera and software, with quantitative volume
      measurements evaluating the amount of postoperative volume change. RESULTS:
      Thirty-three patients (66 hemiface-midface regions) were included in the study.
      The mean follow-up time was 16 months. The mean amount of autologous fat injected
      into each midface region was 10.1 mL. Overall, the mean absolute volume
      augmentation measured at their last postoperative visit was 3.3 mL (31.8% take).
      There was variability between patients in the volume amount and percentage that
      remained. Touch-up procedures were performed in 8 patients. CONCLUSIONS: To our
      knowledge, this study is the first clinical quantification of autologous fat
      transfer and/or grafting in the literature that provides definitive evidence on
      the amount as well as the resultant longevity in the midface. Autologous fat
      transfer to the midface has definite long-term volume augmentation results. On
      average, approximately 32% of the injected volume remains at 16 months. However,
      some variability exists in the percentage of volume that remains that may require
      a touch-up procedure.

PMID- 19153290
TI  - Efficacy of Crosseal fibrin sealant (human) in rhytidectomy.
AB  - OBJECTIVE: To examine the potential efficacy of Crosseal (the human protein,
      bovine component-free fibrin sealant) (OMRIX Biopharmaceuticals, Ltd, Brussels,
      Belgium) to reduce ecchymoses and hematoma formation in patients undergoing
      rhytidectomy. METHODS: Before initiation of the study, approval was obtained from
      the US Food and Drug Administration for an Investigational New Drug Application
      and off-label use of Crosseal and from the Institutional Review Board of the
      University of California, Davis. Patients undergoing rhytidectomy with or without
      concomitant procedures were voluntarily enrolled without compensation in the
      study (N = 9). Patients were randomized according to which side of the
      rhytidectomy the tissue sealant was placed. In all patients in the study, 1 side
      of the rhytidectomy was treated with Crosseal; the other, untreated side was used
      as a control. Before closure of the skin, 2 mL of Crosseal was sprayed through a
      pressure regulator under the skin flap of the dissected area of the rhytidectomy
      only on 1 side. The skin was pretrimmed before placement and closed in standard
      fashion. A pressure dressing was left in place for 3 days before removal. Nine
      patients were originally enrolled in the study. On postoperative days 3 and 7,
      photographs were taken of the patients. The photographs were judged by 5
      independent reviewers who were blinded as to which side had been treated with
      Crosseal. The judges rated the degree of ecchymoses on a scale of 1 (minimal) to
      10 (severe) and were asked their opinion as to which side of the facelift had
      been treated with Crosseal. These results were compared using statistical
      analysis. Also on days 3 and 7, patients were examined for seroma or hematoma
      formation on each side of the face. RESULTS: Our study demonstrated efficacy of
      Crosseal in reducing ecchymoses and swelling in all patients. The mean score for
      ecchymosis on the Crosseal-treated side was 4.5 and on the untreated (control)
      side was 6.2 (P < .01, Wilcoxon rank sum test). The rate of hematoma or seroma
      formation was 22% (2 of 9 patients) for the untreated side vs 0% (0 of 9
      patients) for the treated side. This did not reach statistical significance (P =
      .43, Fisher exact test). Small hematomas developed in 2 patients on the control
      side, which were needle aspirated. There were no known long-term complications
      from either the use of Crosseal or the rhytidectomy. CONCLUSION: Crosseal is
      efficacious in reducing ecchymoses after rhytidectomy.

PMID- 19153291
TI  - Brow elevation ratio: a new method of brow analysis.
AB  - OBJECTIVE: To introduce a novel quantitative method measuring preoperative and
      postoperative brow position and apply it to a cohort of patients undergoing
      endoscopic brow suspension. DESIGN: Retrospective review of patients who
      underwent endoscopic brow- and forehead-lift using a consistent operative
      technique and method of fixation. Changes in brow position were measured using
      standardized digital photographs of patients taken before and after surgery. Brow
      elevation was determined using a novel measurement system based on the ratio of
      the vertical height of the brow to the distance between the lateral corneal
      limbus and the medial canthus. RESULTS: Sixteen consecutive patients (32
      eyebrows) underwent surgery between January 7, 2003, and January 15, 2006,
      without any major complications. With follow-up ranging from 6 to 31 months (mean
      follow-up, 18 months), a statistically significant elevation of brow position was
      found. Mean brow ratio measurements increased by 18.0% on the right side and
      16.1% on the left side, for an overall mean increase in brow position of 17.1%.
      The brow elevation ratio remained increased by a mean of 16.8% for patients who
      were followed up for almost 2 years and beyond. CONCLUSIONS: The brow elevation
      ratio can be applied to patients undergoing brow suspension procedures with
      standard office photography. The ratios provide the surgeon with a quantitative
      dimension for assessing outcomes of brow elevation and can be used in comparative
      analysis of each patient's baseline brow position.

PMID- 19153292
TI  - Injectable cartilage: using alginate and human chondrocytes.
AB  - OBJECTIVE: To create engineered cartilage through an injectable medium that could
      be used as a minimally invasive implant material. METHODS: Human nasal septal
      chondrocytes, carried in an alginate polymer, were injected and molded
      percutaneously into nude mice and developed in vivo. The cartilage was harvested
      from 14 to 38 weeks and analyzed through gross, histological,
      immunohistochemical, and biochemical analysis. RESULTS: Of the 15 explants, 14
      (93%) resembled native cartilage on gross analysis. The injections maintained
      their overall appearance with some loss of definition. On histological analysis,
      6 of the explants (40%) appeared similar to native cartilage throughout the
      sample. Eight of the explants (53%) resembled native cartilage; however, there
      were some areas of fibrous tissue differentiation. The neocartilage stained
      positive for type II collagen. Explants harvested at week 26 or later and the
      samples that histologically resembled native cartilage had similar hydroxyproline
      content to native septal cartilage. CONCLUSIONS: Injectable, autologous cartilage
      may be the answer to the long search for the ideal implant in facial plastic
      surgery. Alginate and human chondrocytes can be used to create an injection that
      may be molded and maintains its overall size and shape, with some loss of
      definition, for at least 38 weeks after injection.

PMID- 19153293
TI  - Maxillofacial injuries and violence against women.
AB  - OBJECTIVE: To determine if patterns of facial injuries differed between those of
      female assault victims with maxillofacial injuries and those of female patients
      with maxillofacial injuries from other causes. METHODS: We reviewed the medical
      and dental records of 326 adult female facial trauma patients treated by
      otolaryngologists and oral/maxillofacial surgeons at the University of Kentucky
      Medical Center. Information abstracted included date of injury, dates of
      presentation for medical attention, mechanism(s) of injury, diagnoses, and
      treatments. RESULTS: While victims of intimate partner violence were more likely
      to have zygomatic complex fractures, orbital blow-out fractures, and intracranial
      injuries than were other patients with facial trauma, women assaulted by unknown
      or unidentified assailants were more likely to have mandible fractures (P =
      .004). CONCLUSION: These results in conjunction with other presenting
      circumstances, such as delay in presentation, can assist the surgeon treating
      patients with maxillofacial injury in recognizing interpersonal violence against
      women.

PMID- 19153294
TI  - Use of customized polyetheretherketone (PEEK) implants in the reconstruction of
      complex maxillofacial defects.
AB  - Extensive maxillofacial defects resulting from trauma or oncologic resection
      present reconstructive challenges. Various autografts and alloplastic materials
      in conjunction with standard soft-tissue techniques have been used in the
      reconstruction of these types of defects. Polyetheretherketone (PEEK) is a
      semicrystalline polyaromatic linear polymer exhibiting an excellent combination
      of strength, stiffness, durability, and environmental resistance. Recent
      investigations of PEEK as a biomaterial resulted in the successful treatment of
      cervical disk disease. We describe a series of 4 patients whose defects were
      reconstructed using customized PEEK implants. All had excellent postoperative
      aesthetic and functional results without complications such as infections or
      extrusions. Because PEEK implants are customizable, easily workable, inert, and
      nonporous, they represent an ideal alloplastic material for maxillofacial
      reconstruction.

PMID- 19153295
TI  - Image-guided titanium implantation for craniofacial prosthetics.
AB  - Osseointegration implants have revolutionized craniofacial prosthetic
      reconstruction. Implant placement relies on adequate thickness and quality of
      bone to permit osseointegration. Positioning the implant is critical in
      craniofacial reconstruction because surface contours of the prosthesis must be
      preserved while housing attachment components securely and discretely. Also, the
      position of the final prosthesis must transition to native tissue smoothly. We
      report on the use of intraoperative stereotactic image guidance in the placement
      of implants for orbital, nasal, and auricular prosthetic reconstruction. Clinical
      data, intraoperative images, and postoperative rehabilitated results are
      presented to demonstrate the utility of the application of stereotactic image
      guidance for implant placement. In our experience, stereotactic image guidance
      facilitates optimal implant site selection if there is abnormal bone quantity or
      quality.

PMID- 19153296
TI  - Carbon dioxide laser resurfacing.

PMID- 19153297
TI  - Internal nasal valve collapse.

PMID- 19153299
TI  - Pablo Picasso's Girl Before a Mirror: the agony of imagined ugliness.

PMID- 19153300
TI  - Pediatric otolaryngology in the United States: demographics, workforce
      perceptions, and current practices.
AB  - OBJECTIVES: To evaluate self-reported workforce needs and demands, professional
      activities, and the clinical practices of pediatric otolaryngologists in the
      United States for the purpose of better understanding the pediatric
      otolaryngology workforce and predicting manpower needs. DESIGN: A Web-based
      survey was sent to all members of the American Society of Pediatric
      Otolaryngology (ASPO). It achieved a 39.3% response rate, with a total of 99 US
      member respondents. We compared this sample to the overall US ASPO membership to
      determine if our respondent cohort was representative of ASPO demographics.
      PARTICIPANTS: All members of ASPO. MAIN OUTCOME MEASURES: Responses were
      categorized by demographics and nature of respondent practice (academic vs
      private practice). RESULTS: Respondents were representative of the US ASPO
      membership. Most of the respondents practiced in an academic setting (n = 70;
      70%). Academicians reported seeing a higher percentage of patients with Medicaid
      public insurance than did private practitioners (34% vs 25.0%) (P = .03).
      Academicians spent a greater portion of their time than private practitioners on
      research (14.4% vs 6.6% of time) (P < .001) and teaching (26.9% vs 12.8% of time)
      (P = .002). With the exception of choanal atresia repair, there were no
      differences in the types of airway, otologic, head and neck, and plastic and
      reconstructive surgery performed by the 2 groups. Although fewer than half of the
      respondents (47%; n = 44) believed that there presently is a shortage of
      pediatric otolaryngology manpower, most (68%; n = 63) (P = .01) believed that
      there would be a shortage in 5 years. CONCLUSIONS: Pediatric otolaryngologists
      predict an increased demand for their services in the near future. The only
      differences in the clinical practices of academic and private pediatric
      otolaryngologists are patient payer mix and the amount of time devoted to
      teaching.

PMID- 19153301
TI  - Nationwide trends in pediatric Staphylococcus aureus head and neck infections.
AB  - OBJECTIVES: To evaluate the epidemiologic manifestations of pediatric
      Staphylococcus aureus head and neck infections nationwide and to identify
      possible trends in the antibiotic drug susceptibility of S aureus during a 6-year
      period. DESIGN: Retrospective review of microbiologic data from a peer-reviewed
      national database. SETTING: More than 300 hospitals nationwide. PATIENTS: All
      pediatric patients with head and neck infections involving S aureus. MAIN OUTCOME
      MEASURES: Anatomic sites were divided into oropharynx/neck, sinonasal, and
      otologic infection categories. Demographic and antimicrobial drug susceptibility
      patterns were reviewed. RESULTS: A total of 21,009 pediatric head and neck S
      aureus infections that occurred between January 2001 and December 31, 2006 were
      gathered from the database. Predominance was observed in the oropharyngeal/neck
      category (60.3%). For all sites, the mean patient age was 6.7 years (range, 0-18
      years), with a 51.7% male predominance. There was a high occurrence in the North
      East Central region of the United States. Overall, methicillin-resistant S aureus
      was seen in 21.6% of all patient isolates (n = 4534), with rates of 11.8%, 12.5%,
      18.1%, 27.2%, 25.5%, and 28.1% for 2001 through 2006, respectively. This
      represents a 16.3% increase in methicillin-resistant S aureus during these 6
      years for all pediatric head and neck S aureus infections. CONCLUSIONS: There is
      an alarming nationwide increase in the prevalence of pediatric methicillin
      resistant S aureus head and neck infections. Disparities in the treatment of
      various head and neck infections nationwide may contribute to the regional
      differences in the prevalence of such infections. Judicious use of antibiotic
      agents and increased effectiveness in diagnosis and treatment are warranted to
      reduce further antimicrobial drug resistance in pediatric head and neck
      infections.

PMID- 19153302
TI  - Rate of concurrent otitis media in upper respiratory tract infections with
      specific viruses.
AB  - OBJECTIVE: To estimate the coincidence of new otitis media (OM) for first
      nasopharyngeal detections of the more common viruses by polymerase chain reaction
      (PCR). New OM episodes are usually coincident with a viral upper respiratory
      tract infection (vURTI), but there are conflicting data regarding the association
      between specific viruses and OM. DESIGN: Longitudinal (October-March),
      prospective follow-up of children for coldlike illness (CLI) by diary, middle ear
      status by pneumatic otoscopy, and vURTI by PCR. SETTING: Academic medical
      centers. PARTICIPANTS: A total of 102 families with at least 2 children aged
      between 1 and 5 years (213 children; mean [SD] age, 3.7 [1.5] years; 110 male;
      and 176 white) were recruited from the local communities at 2 study sites by
      advertisement. MAIN OUTCOME MEASURES: New OM and CLI episodes and nasopharyngeal
      virus detections. RESULTS: A total of 176 children (81%) had isolated PCR
      detection of at least 1 virus. The OM coincidence rates were 62 of 144 (44%) for
      rhinovirus, 15 of 27 (56%) for respiratory syncytial virus, 8 of 11 (73%) and 1
      of 5 (20%) for influenza A and B, respectively, 6 of 12 (50%) for adenovirus, 7
      of 18 (39%) for coronavirus, and 4 of 11 (36%) for parainfluenza virus detections
      (P = .37). For rhinovirus, new OM occurred in 50% of children with and 32%
      without a concurrent CLI (P = .15), and OM risk was predicted by OM and
      breastfeeding histories and by daily environment outside the home. CONCLUSIONS:
      New OM was associated with nasopharyngeal detection of all assayed viruses
      irrespective of the presence or absence of a concurrent CLI. Differences among
      viruses were noted, but statistical significance was not achieved, possibly
      because of the low power associated with the small number of nonrhinovirus
      detections.

PMID- 19153303
TI  - Rapid maxillary expansion for the treatment of nasal obstruction in children
      younger than 12 years.
AB  - OBJECTIVE: To assess short- and long-term effects of rapid maxillary expansion
      (RME) on nasal flow in young children. Since RME has been reported to positively
      influence nasal obstruction in subjects with respiratory problems by reducing
      nasal resistance, a similar efficacy of RME could be expected in children with
      deciduous and/or mixed dentition who are affected by maxillary constriction and
      nasal obstruction from a different cause. DESIGN: Prospective study of children
      younger than 12 years, with different grades of malocclusion and oral breathing.
      Data included active anterior rhinomanometry in both the supine and orthostatic
      positions, as well as radiographic cephalometric measurements. SETTING: Tertiary
      care university hospital. Data were prospectively collected from 2005 to 2007.
      PATIENTS: Nasal flow and resistance were measured in 65 children younger than 12
      years, with mixed or deciduous dentition and different grades of malocclusion and
      oral breathing. MAIN OUTCOME MEASURE: Efficacy of RME for resolution of maxillary
      constriction. RESULTS: After RME, an improvement of nasal flow and resistance has
      been recorded in patients, in the supine position, who presented both anterior
      and posterior obstruction. Less notable changes were shown in isolated forms of
      obstruction and in the orthostatic position. CONCLUSION: In cases of maxillary
      constriction and nasal airway obstruction, RME has proved to be efficient for the
      improvement of nasal respiration in children via a widening effect on the
      nasopharyngeal cavity.

PMID- 19153304
TI  - Existence of important variations in the United States in the treatment of
      pediatric mastoiditis.
AB  - OBJECTIVE: To determine national variations in resource utilization in the
      treatment of pediatric mastoiditis. DESIGN: Retrospective review. SETTING:
      National pediatric inpatient database. PATIENTS: The Kids' Inpatient Database for
      2003 was used to extract data for admissions for mastoiditis. RESULTS: A total of
      1049 patients (57% were male, and the mean age was 6.3 years) were identified.
      Median total charges for an admission were $9600; total charges were less than
      $28,604 in 90% of admissions. The mean length of stay (LOS) was 4.3 days (range,
      0-87 days). A total of 792 procedures were performed; 50.0% of patients underwent
      tympanostomy tube placement and/or myringocentesis, and 21.6% underwent
      mastoidectomy. The LOS for nonsurgical patients was 3.7 days. The LOS for
      children undergoing tube placement was 4.6 days, with mean total charges of
      $15,713; for mastoidectomy, the LOS was 5.5 days, with mean total charges of
      $23,185. The primary payer was private insurance in 51.5% and Medicaid in 39.4%.
      Predictors of increased charges were treatment at teaching hospitals (P = .005),
      treatment at children's hospitals (P < .001), LOS (P < .001), the number of
      procedures (P < .001), and hospital region (P = .003). Wide geographic variation
      was noted with respect to the mean total charges per admission, which ranged from
      $5016 to $35,898. CONCLUSIONS: In 2003, the median charge for a pediatric
      mastoiditis admission was $9600; 50% of patients underwent tympanostomy tube
      placement, and about 21.6% underwent a mastoidectomy. There was wide variation in
      total charges for admissions. Resource utilization was higher in teaching
      hospitals and in children's' hospitals.

PMID- 19153305
TI  - Gene expression differences in infected and noninfected middle ear complementary
      DNA libraries.
AB  - OBJECTIVES: To investigate genetic differences in middle ear mucosa (MEM) with
      nontypeable Haemophilus influenzae (NTHi) infection. Genetic upregulation and
      downregulation occurs in MEM during otitis media (OM) pathogenesis. A
      comprehensive assessment of these genetic differences using the techniques of
      complementary DNA (cDNA) library creation has not been performed. DESIGN: The
      cDNA libraries were constructed from NTHi-infected and noninfected chinchilla
      MEM. Random clones were picked, sequenced bidirectionally, and submitted to the
      National Center for Biotechnology Information (NCBI) Expressed Sequence Tags
      database, where they were assigned accession numbers. These numbers were used
      with the basic local alignment search tool (BLAST) to align clones against the
      nonredundant nucleotide database at NCBI. RESULTS: Analysis with the Web-based
      statistical program FatiGO identified several biological processes with
      significant differences in numbers of represented genes. Processes involved in
      immune, stress, and wound responses were more prevalent in the NTHi-infected
      library. S100 calcium-binding protein A9 (S100A9); secretory leukoprotease
      inhibitor (SLPI); beta(2)-microglobulin (B2M); ferritin, heavy-chain polypeptide
      1 (FTH1); and S100 calcium-binding protein A8 (S100A8) were expressed at
      significantly higher levels in the NTHi-infected library. Calcium-binding
      proteins S100A9 and S100A8 serve as markers for inflammation and have
      antibacterial effects. Secretory leukoprotease inhibitor is an antibacterial
      protein that inhibits stimuli-induced MUC1, MUC2, and MUC5AC production.
      CONCLUSIONS: A number of genes demonstrate changes during the pathogenesis of OM,
      including SLPI, which has an impact on mucin gene expression; this expression is
      known to be an important regulator in OM. The techniques described herein provide
      a framework for future investigations to more thoroughly understand molecular
      changes in the middle ear, which will likely be important in developing new
      therapeutic and intervention strategies.

PMID- 19153306
TI  - Assessment of saccular function in children with sensorineural hearing loss.
AB  - OBJECTIVE: To investigate saccular function using vestibular evoked myogenic
      potentials in children with congenital or early acquired sensorineural hearing
      loss. DESIGN: Retrospective cohort study. SETTING: Pediatric tertiary referral
      center. PATIENTS: Twenty-three children with bilateral sensorineural hearing loss
      (severe to profound in 22 cases, moderate in 1 case) underwent evaluation of
      saccular function. Twelve pediatric subjects with normal hearing were included in
      the study as the control group. INTERVENTIONS: Otologic examination, computed
      tomography of the temporal bone, audiometry, tympanometry, and vestibular evoked
      myogenic potential testing. MAIN OUTCOME MEASURE: Differences in threshold,
      amplitude, and P1 and N1 latencies of vestibular evoked myogenic potentials
      between children with normal-hearing and hearing-impaired children. RESULTS:
      Abnormal vestibular evoked myogenic potentials were found in 21 of 23 children
      (91%) with sensorineural hearing loss. The thresholds of vestibular evoked
      myogenic potential were significantly higher (P <.001) and the amplitudes were
      lower in children with sensorineural hearing loss than those in children with
      normal hearing. There were no differences in the P1 and N1 latencies between the
      2 groups. CONCLUSIONS: The impairment of saccular function, indicated by the
      abnormal findings in the vestibular evoked myogenic potential, is often
      associated with sensorineural hearing loss in the pediatric population. Although
      saccular dysfunction may create a vestibular deficit, its manifestations can vary
      and be easily overlooked in children. Considering the high percentage of abnormal
      findings in our study, we recommend that deaf and hard-of-hearing children
      undergo vestibular evaluation. Vestibular evoked myogenic potential testing is an
      easy and reliable procedure to evaluate saccular function in children.

PMID- 19153307
TI  - A novel murine model for the examination of experimental subglottic stenosis.
AB  - OBJECTIVE: To develop a novel mouse model of acquired subglottic stenosis (SGS)
      using heterotopic transplanted laryngotracheal complexes (LTCs). DESIGN: Pilot
      randomized controlled animal study. SUBJECTS: Forty-eight C57BL/6 mice.
      INTERVENTIONS: Twenty-four donor C57BL/6 mice underwent LTC harvesting. The LTCs
      were then implanted deep to a cutaneous dorsal flap in 24 allogenic recipients.
      Sixteen LTCs underwent direct subglottic injury before transplantation, while 8
      control LTCs were transplanted without injury. Transplanted LTCs were harvested
      1, 2, 3, and 4 weeks after surgery. Tissues were fixed and cut transversely in 6
      microm sections from the larynx to the second tracheal ring. Movat pentachrome
      staining was performed for connective tissue and morphometric analysis. Digital
      images of the subglottis were captured at x 20 magnification. The thicknesses of
      the lamina propria and the epithelium were measured at 5 random and equally
      spaced locations within the subglottic lumen. Vascular endothelial growth factor
      164 (VEGF 164) and transforming growth factor beta1 (TGF-beta1)
      immunohistochemistry was performed on representative sections. RESULTS: Lamina
      propria thickness was significantly greater in transplanted LTCs 3 and 4 weeks
      after injury compared with controls (P = .03, P = .01, respectively). Combined
      results (groups harvested at 1-4 weeks) revealed a significant difference between
      all 8 control animals and all 16 experimental animals (P < .001). Epithelial
      thickness was also greater in the transplanted LTCs 2, 3, and 4 weeks after
      injury to the subglottis compared with controls (P = .04 for weeks 2 through 4).
      Movat pentachrome staining showed random distributions and high concentrations of
      connective tissue within the lamina propria of the subglottis. The VEGF 164 and
      TGF-beta1 staining patterns were consistent with previous in vivo models of SGS.
      CONCLUSION: Heterotopic transplanted LTCs in mice can provide an inexpensive and
      flexible model for experimental investigation of acquired SGS.

PMID- 19153308
TI  - Optical microscopy of the pediatric vocal fold.
AB  - OBJECTIVES: To compare and contrast 4 optical imaging techniques for evaluating
      the developing microstructure of the pediatric vocal fold and to identify the
      optimal strategy for in vivo imaging. DESIGN: Prospective study. SETTING:
      Academic medical center. PATIENTS: A total of 6 laryngeal specimens: 5 pediatric
      (ages 10 months to 16 years) (4 from cadavers and 1 from a living patient
      immediately after laryngectomy) and 1 cadaveric young adult specimen (age, 23
      years). INTERVENTION: Sequential noninvasive optical imaging of pediatric vocal
      fold specimens using optical frequency domain imaging (OFDI), angle-resolved OFDI
      (AR-OFDI), spectrally encoded confocal microscopy (SECM), and full-field optical
      coherence microscopy (FF-OCM), followed by fixation, sectioning, and histologic
      analysis of the same specimen for comparison. MAIN OUTCOME MEASURE: Correlation
      between the microstructure observed using the 4 noninvasive optical imaging
      techniques and with the results of histopathologic analysis for the same
      specimen. RESULTS: A successful in vivo imaging technique for developmental
      assessment of the pediatric vocal fold would include visualization of distinct
      layers (epithelium, lamina propria, and muscularis mucosa) and allow for
      identification of the individual cells composing the layers. The OFDI and AR-OFDI
      techniques provide a global assessment of the microstructure of the pediatric
      vocal fold to a depth of 1200 mum but lack the ability to distinguish cellular
      and subcellular structures. The FF-OCM technique allows for visualization with
      improved cellular detail (1-mum resolution), but the image acquisition speed is
      too slow for clinical use. The SECM technique has a faster acquisition rate and
      shows good cellular and subcellular detail to a depth of 250 mum. CONCLUSIONS:
      The OFDI and SECM techniques were identified as promising and complementary
      candidates for in vivo cellular and subcellular imaging of the epithelium,
      basement membrane, and lamina propria of the pediatric vocal fold. To further
      validate the clinical potential of these techniques, a handheld SECM probe has
      been developed and demonstrated for in vivo evaluation of the pediatric vocal
      fold.

PMID- 19153310
TI  - Airway management in children with mucopolysaccharidoses.
AB  - OBJECTIVE: To review of the natural history of airway disease in children with
      muccopolysaccharidoses (MPSs), which represent a group of hereditary progressive
      disorders caused by excessive accumulation of glycosaminoglycans in various
      tissues. DESIGN: Retrospective medical chart review. SETTING: Tertiary referral
      academic medical center. PATIENTS: Twenty-seven children with MPSs. MAIN OUTCOME
      MEASURES: A review of the medical charts of 27 children with MPSs between
      February 1, 1984, and February 1, 2004, was performed to examine the natural
      history of airway disease. RESULTS: Clinically upper airway obstruction was noted
      in 19 patients (70%) and necessitated a tracheotomy in 3 patients (11%). Fourteen
      of the 27 patients underwent bone marrow transplantation, and successful
      engraftment resulted in a significant decrease in obstructive symptoms in 13 of
      the 14 patients. CONCLUSIONS: Patients affected by MPSs require the vigilant
      attention of the otolaryngologist, as sleep apnea and upper airway obstruction
      are common complications. Successful bone marrow engraftment may alter the
      natural history of airway disease and result in substantial improvement in
      symptomatic airway disease in children with MPSs.

PMID- 19153309
TI  - Expression profiling of inflammatory mediators in pediatric sinus mucosa.
AB  - OBJECTIVE: To evaluate gene expression by microarray analyses of inflammatory
      mediators in the sinus mucosa of children with and without chronic rhinosinusitis
      (CRS). DESIGN: Prospective molecular genetics analysis. SETTING: Children's
      National Medical Center, Washington, DC. SUBJECTS: Eleven patients with CRS who
      underwent endoscopic sinus surgery and 10 control children who underwent
      craniofacial resection or neurosurgical procedures. MAIN OUTCOME MEASURES: Gene
      expression levels of sinus tissue from 6 patients with CRS and 6 controls and
      messenger RNA expression levels of upregulated inflammatory/immune response
      genes, as well as cytokines of interest, determined by quantitative reverse
      transcription-polymerase chain reaction. RESULTS: Gene expression using the Plier
      algorithm yielded the most consistent grouping of samples: 96 genes were
      significantly upregulated more than 2-fold, and 123 genes were downregulated by
      at least 50% in the CRS sinus tissues compared with controls (P < .05).
      GeneSpring analysis demonstrated significant changes in several ontology
      categories in the CRS samples, including inflammatory/immune response genes. The
      chemokines CXCL13 and CXCL5, serum amyloid A, serpin B4, and defensin beta1 were
      highly upregulated (> or =5-fold). Increased expression of these genes was
      validated by quantitative reverse transcription-polymerase chain reaction in an
      independent set of tissues. Expression levels of interleukins 5, 6, and 8 were
      similar in both cohorts; these results were validated by reverse transcription
      polymerase chain reaction. CONCLUSIONS: Microarray analyses of sinus mucosa in
      children with CRS showed an increased expression of inflammatory genes involved
      in innate and adaptive immune systems. This technology can be successfully used
      to identify genes implicated in the pathogenesis of pediatric CRS.

PMID- 19153311
TI  - Long-term results of innominate artery reimplantation for tracheal compression.
AB  - OBJECTIVE: To evaluate the safety and long-term efficacy of innominate artery
      reimplantation as treatment for innominate artery compression syndrome. DESIGN:
      Retrospective medical record review from January 1, 1992, to December 31, 2007,
      and telephone interview. SETTING: Children's hospital. PATIENTS: Twenty-two
      children with innominate artery compression of the trachea requiring surgical
      intervention. INTERVENTION: Innominate artery reimplantation for innominate
      artery compression syndrome. MAIN OUTCOME MEASURES: Respiratory symptoms, rigid
      bronchoscopy results, operative time, estimated blood loss, duration of
      hospitalization, and complications. RESULTS: Twenty-two patients were seen with
      innominate artery compression of the trachea causing respiratory distress. The
      diagnosis was made based on chest magnetic resonance images, computed tomographic
      angiograms, and rigid bronchoscopy results demonstrating significant (>75%)
      tracheal stenosis. Following innominate artery reimplantation, 19 patients (86%)
      had complete resolution of symptoms and discontinuation of respiratory support.
      Two patients had partial resolution, and 1 patient had no improvement. The time
      course of resolution was immediate in 13 patients, after 3 months in 1 patient,
      and unknown in 5 patients. The mean operative time was 73 minutes, with a mean
      estimated blood loss of 18 mL. The mean postoperative duration of hospitalization
      was 6.5 days, with a mode and median stay of 3 days. One patient required
      prolonged intubation (5 days), and another patient developed postpericardiotomy
      syndrome. Telephone interview of 10 patients at a mean of 5 years after surgery
      revealed continued resolution of respiratory symptoms if previously resolved and
      no long-term complications. CONCLUSIONS: Innominate artery reimplantation is a
      safe and effective treatment for innominate artery compression syndrome.
      Resolution of symptoms occurs quickly in most patients, with excellent long-term
      results.

PMID- 19153312
TI  - The role of tonsillectomy in pediatric IgA nephropathy.
AB  - OBJECTIVES: To review pediatric cases of IgA nephropathy (IgAN) in 6 patients who
      underwent tonsillectomy and had marked improvement of their renal symptoms and to
      review the appropriate indications for tonsillectomy for this disease. DESIGN:
      Retrospective case series. SETTING: Academic medical center. PATIENTS: Six
      children (age range, 8-15 years) with renal biopsy-proved IgAN who were referred
      by a pediatric nephrologist for recurrent tonsillitis. INTERVENTION:
      Tonsillectomy. MAIN OUTCOME MEASURES: Resolution of clinical features of IgAN,
      including proteinuria, gross and microscopic hematuria, and stabilization of
      renal function. RESULTS: The 6 patients in this series had marked clinical and
      laboratory improvement of their nephropathy. CONCLUSIONS: In a select group of
      pediatric cases of IgAN with mild to moderate disease and recurrent tonsillitis,
      tonsillectomy can be a useful adjuvant treatment to improve urinary symptoms and
      renal function. IgA nephropathy is a common indication for tonsillectomy in Japan
      but is seen less often in the United States. Otolaryngologists should be aware of
      this indication for tonsillectomy.

PMID- 19153313
TI  - Recurrent laryngeal nerve monitoring during thyroidectomy and related cervical
      procedures in the pediatric population.
AB  - OBJECTIVES: To gather data on, and assess the applicability of, intraoperative
      recurrent laryngeal nerve (RLN) monitoring during thyroidectomy and related
      cervical procedures in children and adolescents. Recurrent laryngeal nerve trauma
      is one of the most serious complications of surgery in the anterior neck
      compartment. Numerous studies have demonstrated the utility of intraoperative
      monitoring of the RLN in adult thyroid surgery to prevent such injury. Although
      the risk of RLN injury is reportedly higher in the pediatric population, little
      data exist regarding the use of intraoperative RLN monitoring in children and
      adolescents. DESIGN: Retrospective case series review. SETTING: A pediatric
      otolaryngology practice in a tertiary care hospital. PATIENTS: Five patients
      undergoing surgical excision of thyroid neoplasms or branchial pouch anomalies.
      INTERVENTIONS: During surgical excision, intraoperative RLN monitoring was
      performed with use of the Xomed NIM II monitor and Xomed RLN monitoring
      endotracheal tube, which allow for both passive and stimulation-evoked
      electromyographic monitoring of the thyroarytenoid muscle. MAIN OUTCOME MEASURES:
      True vocal fold mobility as assessed by postoperative flexible laryngoscopy.
      RESULTS: Intraoperative RLN monitoring was performed successfully for up to 4
      hours. Such monitoring facilitated the identification of the RLN and was
      predictive of the subsequent presence or absence of postoperative RLN paresis.
      CONCLUSIONS: Intraoperative RLN monitoring can be a useful tool during cervical
      procedures that place the RLN at risk in children and adolescents. As has been
      demonstrated in adults, it is a safe and reliable technique that can be
      predictive of and may lessen the risk of RLN morbidity in this younger patient
      population.

PMID- 19153314
TI  - Eosinophilic esophagitis in children: a pathologic or clinicopathologic
      diagnosis?
AB  - OBJECTIVE: To determine the accuracy of histopathologic diagnosis in
      distinguishing eosinophilic esophagitis (EE) from gastroesophageal reflux disease
      (GERD) in children with upper aerodigestive symptoms. DESIGN: Masked review of
      esophageal biopsy findings and comparison with each child's established clinical
      diagnosis. SETTING: A tertiary care multidisciplinary aerodigestive center.
      PATIENTS: Children were selected from a longitudinal database of all children
      referred for upper aerodigestive symptoms who underwent a comprehensive
      evaluation between September 1, 2004, and September 1, 2007. Three groups were
      recognized based on clinical presentation, initial histologic review, and
      therapeutic response: children with EE, GERD, or neither. INTERVENTION: Review of
      esophageal biopsy findings by a pathologist masked to the child's clinical or
      previous pathologic diagnosis. MAIN OUTCOME MEASURE: Masked histopathologic
      diagnosis of EE, GERD, or neither. RESULTS: Medical records from 31 patients were
      reviewed (11 children with EE, 10 with GERD, and 10 with neither). Diagnostic
      concurrence between the masked pathologic diagnosis and the established
      clinicopathologic diagnosis was 64% in children with EE, 70% in children with
      GERD, and 100% in children with neither. The 4 cases of EE that did not concur
      were misclassified as GERD when esophageal specimens were evaluated by
      histopathologic means alone. A clinicopathologic schema for EE developed by
      gastroenterologists accurately identified 82% of children with EE. CONCLUSIONS:
      The distinction between EE and GERD cannot be reliably made on histopathologic
      evidence alone in children with upper aerodigestive symptoms. Despite the recent
      gastroenterology consensus statement regarding the clinicopathologic diagnosis of
      EE, children with primary airway symptoms in whom EE is suspected represent a
      diagnostic dilemma.

PMID- 19153315
TI  - The natural history of vincristine-induced laryngeal paralysis in children.
AB  - OBJECTIVE: To outline the natural history of vincristine-induced laryngeal
      paralysis (VLP) in children. DESIGN: Retrospective case series and review of
      reported cases in the English-language literature. SETTING: Tertiary pediatric
      center. PATIENTS: The study included all children with a confirmed diagnosis of
      VLP by inspection and with complete clinical information. The sources for patient
      identification were a prospectively kept database and a review of the English
      language literature, conducted on PubMed since 1966, as well as a bibliography
      search. MAIN OUTCOME MEASURES: Charts and literature were reviewed for
      demographics, primary diagnosis, other diagnoses, and duration and method of
      treatment. The prevalence of VLP, locally, was also calculated. RESULTS: Four
      children (3 boys and 1 girl) were identified in our database over a 5(1/2)-year
      period, and 10 children (1 girl, 8 boys, and 1 with sex omitted) were described
      in the English-language literature. Four children had unilateral vocal fold
      paralysis only, all left-sided. The median age was 2.6 years. Acute lymphoblastic
      leukemia was the underlying diagnosis in 8 patients. Two patients had Down
      syndrome, and 1 patient had Charcot-Marie-Tooth disease, type 1. Only 2 patients
      required tracheotomies, and 1 patient was treated temporarily with bilevel
      positive-pressure ventilation. The median duration of paralysis was 6.8 weeks.
      The prevalence of VLP was 1.36%. CONCLUSIONS: The data suggest that VLP is
      probably underreported and possibly underdiagnosed. Endoscopic inspection is a
      must in all patients with airway symptoms who are receiving vincristine therapy.
      Early recognition of VLP is mandatory, as it is reversible, has a good prognosis,
      and usually needs only interruption of vincristine therapy and conservative
      treatment.

PMID- 19153317
TI  - Attending work hour restrictions: is it time?

PMID- 19153318
TI  - Outcomes and predictors of mortality and stoma formation in surgical management
      of colonoscopic perforations: a multicenter review.
AB  - OBJECTIVES: To perform a retrospective review of all patients with colonoscopic
      perforations managed in hospitals within the Eastern New Territories region of
      Hong Kong and to determine the predictors of mortality and stoma formation in
      patients with colonoscopic perforations. DESIGN: Retrospective computer-based
      review. SETTING: Multicenter (1 university teaching hospital and 2 district
      hospitals). METHODS: We reviewed the outcomes of patients with colonoscopic
      perforations surgically managed between January 1, 1998, and December 31, 2005.
      Predictors of mortality and stoma formation were identified with multivariable
      analysis. MAIN OUTCOME MEASURES: Mortality and stoma rates and their predictors.
      RESULTS: A total of 37,971 colonoscopies were performed during the study period,
      and 43 colonoscopic perforations were identified. The overall perforation rate
      was 0.113% and represented a decreasing trend. There was no significant
      difference in the perforation rate between gastroenterologists (0.148%) and
      surgeons (0.091%) (P = .15). Perforations that occurred during diagnostic
      colonoscopies were significantly larger than those that occurred during
      therapeutic colonoscopies (P = .04), and the patients presented earlier (P =
      .02). Surgical intervention was performed in 39 patients. The overall morbidity
      and mortality rate was 48.7% and 25.6%, respectively. The stoma rate was 38.5%.
      The predictors of stoma formation include moderate to severe peritoneal
      contamination and the presence of malignant colonic neoplasms (P = .01 and P =
      .008, respectively). The predictors of mortality include American Society of
      Anesthesiologists class 3 or higher and antiplatelet therapy (P = .009 and P =
      .001, respectively). CONCLUSIONS: Colonoscopic perforations were in a decreasing
      trend. Patients with predictors of mortality should not be treated
      conservatively. Other options of large bowel investigations should be considered
      in high-risk patients when the potential diagnostic yield is low.

PMID- 19153319
TI  - Racial disparities among patients with lung cancer who were recommended operative
      therapy.
AB  - HYPOTHESIS: Health care system and provider biases and differences in patient
      characteristics are thought to be prevailing factors underlying racial
      disparities. The influence of these factors on the receipt of care would likely
      be mitigated among patients who are recommended optimal therapy. We hypothesized
      that there would be no significant evidence of racial disparities among patients
      with early-stage lung cancer who are recommended surgical therapy. DESIGN,
      SETTING, AND PATIENTS: Retrospective cohort study of patients in the
      Surveillance, Epidemiology, and End Results-Medicare database who were diagnosed
      with stage I or II lung cancer between January 1, 1992, and December 31, 2002
      (follow-up through December 31, 2005). MAIN OUTCOME MEASURES: Receipt of lung
      resection and overall survival. RESULTS: Among 17,739 patients who were
      recommended surgical therapy (mean [SD] age, 75 [5] years; 89% white, 6% black),
      black patients less frequently underwent resection compared with white patients
      (69% vs 83%, respectively; P < .001). After adjustment, black race was associated
      with lower odds of receiving surgical therapy (odds ratio = 0.43; 99% confidence
      interval, 0.36-0.52). Unadjusted 5-year survival rates were lower for black
      patients compared with white patients (36% vs 42%, respectively; P < .001). After
      adjustment, there was no significant association between race and death (hazard
      ratio = 1.03; 99% confidence interval, 0.92-1.14) despite a 14% difference in
      receipt of optimal therapy. CONCLUSIONS: Even among patients who were recommended
      surgical therapy, black patients underwent lung resection less often than white
      patients. Unexpectedly, racial differences in the receipt of optimal therapy did
      not appear to affect outcomes. These findings suggest that distrust, beliefs and
      perceptions about lung cancer and its treatment, and limited access to care
      (despite insurance) might have a more dominant role in perpetuating racial
      disparities than previously recognized.

PMID- 19153320
TI  - Endoluminal full-thickness plication and radiofrequency treatments for GERD: an
      outcomes comparison.
AB  - HYPOTHESIS: Endoluminal therapies have emerged as adjuncts for the treatment of
      gastroesophageal reflux disease (GERD) in select patients. OBJECTIVE: To compare
      the effectiveness of endoscopic full-thickness plication and endoscopic
      radiofrequency treatments for patients with GERD. PATIENTS: A total of 126
      patients who underwent either endoscopic full-thickness plication (FTP) of the
      gastric cardia or endoscopic radiofrequency (RF) treatment of the esophagogastric
      junction during a 4-year period were included (68 underwent RF and 58 underwent
      FTP). INTERVENTIONS: Follow-up data was obtained for 51% of patients (mean follow
      up, 6 months). MAIN OUTCOME MEASURES: Comparison of medication use, symptom
      scores, and pH values at baseline and follow-up. RESULTS: In the RF group,
      patients with moderate to severe heartburn decreased from 55% to 22% (P < .01),
      and proton pump inhibitor (PPI) use decreased from 84% to 50% (P = .01).
      Decreases were also seen for dysphagia, voice symptoms, and cough. Percentage of
      time the pH was less than 4 was unchanged. In the FTP group, patients with
      moderate to severe heartburn decreased from 53% to 43% (P = .3), and PPI use
      decreased from 95% to 43% (P = .01). Percentage of time the pH was less than 4
      decreased from 10.0% to 6.1% (P = .05). Decreases were also seen for
      regurgitation, voice symptoms, and dysphagia. There was no change in scores for
      chest pain or asthma in either group. CONCLUSIONS: For patients with GERD, RF and
      FTP both resulted in a decrease in both PPI use and in scores for voice symptoms
      and dysphagia. In addition, RF resulted in decreased heartburn and cough, while
      FTP resulted in the most dramatic reduction in regurgitation. Our experience
      indicates that both procedures are effective, providing symptomatic relief and
      reduction in PPI use. For patients whose chief complaint is regurgitation, FTP
      may be the preferred procedure.

PMID- 19153321
TI  - Outcomes of laparoscopic liver resection for lesions located in the right side of
      the liver.
AB  - HYPOTHESIS: Laparoscopic right-sided liver resection may be feasible and safe.
      DESIGN: Retrospective analysis. SETTING: Department of surgery at a university
      hospital. PATIENTS: Of 103 consecutive laparoscopic liver resections performed
      from May 1, 2003, to April 30, 2007, 46 patients underwent a right-sided
      laparoscopic liver resection. Six operations required conversion (13%) to open
      surgery. Overall, data from 40 patients with benign liver tumors (n = 2),
      intrahepatic duct stones (n = 3), liver metastasis from colorectal cancer (n =
      8), and hepatocellular carcinomas (n = 27) were analyzed. MAIN OUTCOME MEASURES:
      Feasibility and operative outcome. RESULTS: The operations included 12 major
      resections (5 right hemihepatectomy and 7 right posterior sectionectomy) and 28
      minor resections (14 segmentectomy and 14 tumorectomy). No operative mortality,
      subsequent operation, or life-threatening complications occurred. Overall, 11
      patients (28%) experienced complications; 2 had bile leakage, 6 had perihepatic
      fluid collection, 2 had prolonged ascites, and 1 had pleural effusion. All
      recovered after conservative management. The mean operation time was 300 minutes,
      the mean blood loss was 620 mL, and the mean hospital stay was 11 days. For
      lesions located at segment VII or VIII (n = 15), the mean operation time and
      amount of blood loss in those receiving a minor liver resection were similar to
      those who received a major resection (P = .21 and .88, respectively). CONCLUSION:
      Although greater technical refinement is required for a minor resection in the
      superior part of the right side of the liver, laparoscopic right-sided liver
      resection is feasible and safe.

PMID- 19153322
TI  - Utility of the surgical apgar score: validation in 4119 patients.
AB  - OBJECTIVES: To confirm the utility of a 10-point Surgical Apgar Score to rate
      surgical outcomes in a large cohort of patients. DESIGN: Using electronic
      intraoperative records, we calculated Surgical Apgar Scores during a period of 2
      years (July 1, 2003, through June 30, 2005). SETTING: Major academic medical
      center. PATIENTS: Systematic sample of 4119 general and vascular surgery patients
      enrolled in the National Surgical Quality Improvement Program surgical outcomes
      database at a major academic medical center. MAIN OUTCOME MEASURES: Incidence of
      major postoperative complications and/or death within 30 days of surgery.
      RESULTS: Of 1441 patients with scores of 9 to 10, 72 (5.0%) developed major
      complications within 30 days, including 2 deaths (0.1%). By comparison, among 128
      patients with scores of 4 or less, 72 developed major complications (56.3%;
      relative risk, 11.3; 95% confidence interval, 8.6-14.8; P < .001), of whom 25
      died (19.5%; relative risk, 140.7; 95% confidence interval, 33.7-587.4; P <
      .001). The 3-variable score achieves C statistics of 0.73 for major complications
      and 0.81 for deaths. CONCLUSIONS: The Surgical Apgar Score provides a simple,
      immediate, objective means of measuring and communicating patient outcomes in
      surgery, using data routinely available in any setting. The score can be
      effective in identifying patients at higher- and lower-than-average likelihood of
      major complications and/or death after surgery and may be useful for evaluating
      interventions to prevent poor outcomes.

PMID- 19153323
TI  - Proposal to subclassify stage IV gastric cancer into IVA, IVB, and IVM.
AB  - OBJECTIVE: This study examined the prognosis of patients with stage IV gastric
      cancer by subgroups after surgical treatment. DESIGN: Retrospective study.
      SETTING: Tertiary care referral center. PATIENTS: A total of 1056 patients with
      stage IV gastric cancer who underwent gastrectomy from January 1, 1995, through
      December 31, 2006, were divided into the following 3 groups: T4N1-3M0 (group 1),
      T1-3N3M0 (group 2), and T(any)N(any)M1 (group 3). MAIN OUTCOME MEASURES: The
      clinicopathological characteristics, recurrence pattern, and survival were
      compared among the 3 groups. RESULTS: There was a significant difference in the
      surgical curability, operation type, Lauren classification, histological
      differentiation, lymphatic invasion, number of lymph nodes retrieved, and
      adjuvant therapy among the 3 groups. The 5-year survival rates in groups 1, 2,
      and 3 were 18.3%, 27.1%, and 9.3%, respectively (P < .001). After R0 resection,
      locoregional recurrence (40.9%) followed by peritoneal recurrence (27.3%) was
      most common in group 1, whereas distant (30.2%) and peritoneal recurrence (26.7%)
      were most common in group 2. Multivariate analysis showed the following
      significant prognostic factors for survival: surgical curability and adjuvant
      therapy for group 1; surgical curability, surgical extent, adjuvant therapy, and
      number of retrieved lymph nodes for group 2; and surgical extent and chemotherapy
      for group 3. CONCLUSIONS: Each subgroup of stage IV gastric cancer had different
      clinical outcomes, including histological behavior, recurrence pattern, survival,
      and prognostic factors. Therefore, subclassification of stage IV gastric cancer
      into IVA (T1-3N3M0), IVB (T4N1-3M0), and IVM (T[any]N[any]M1) might be useful for
      a more accurate prediction of prognosis and selection of appropriate therapeutic
      options.

PMID- 19153324
TI  - Risk factors and management of ascites after liver resection to treat
      hepatocellular carcinoma.
AB  - OBJECTIVES: To identify risk factors for a massive amount of ascites after liver
      resection to treat hepatocellular carcinoma and to evaluate our postoperative
      management strategy. DESIGN: Case-control study. SETTING: University hospital.
      PATIENTS: Two hundred three patients who underwent liver resection to treat
      hepatocellular carcinoma between January 1, 2003, and December 31, 2004. MAIN
      OUTCOME MEASURES: Presence or absence of a large number of ascites (LA), defined
      as postoperative daily ascitic fluid drainage exceeding 10 mL per kilogram of
      body weight, and operative morbidity, mortality, and treatment costs. RESULTS: A
      large number of ascites developed in 31 patients (15%). Multivariate analysis
      revealed that blood loss greater than 1000 mL (relative risk, 6.38; 95%
      confidence interval, 2.19-20.7; P = .001) and preoperative platelet count less
      than 100 x 10(3)/microL (4.75; 1.75-13.1; P = .002) independently increased the
      risk of LA. In patients with LA, urinary output on postoperative days 1 to 3 was
      significantly lower than in patients without LA, and daily ascitic fluid volume
      tended to peak on postoperative day 7. No operative mortality was related to
      liver failure; however, patients with LA required a larger volume of fresh frozen
      plasma than those without LA (median [range], 1600 [0-16 800] mL vs 480 [0-5760]
      mL; P < .001), resulting in higher hospital costs. CONCLUSIONS: Large blood loss
      and low platelet count were independent risk factors for LA. Although it was
      possible to safely manage postoperative ascites using routine administration of
      diuretic agents and fresh frozen plasma, step-by-step trials are required to
      reduce the need for transfusion of fresh frozen plasma.

PMID- 19153325
TI  - Cystic parathyroid lesions: functional and nonfunctional parathyroid cysts.
AB  - HYPOTHESIS: Functional parathyroid cysts (FPCs) and nonfunctional parathyroid
      cysts (NPCs) are 2 distinct clinical and histologic entities. DESIGN: Review of
      prospective clinical database records. SETTING: Tertiary academic center.
      PATIENTS: Patients enrolled in a prospective surgical database between January 1,
      1990, and May 31, 2007. INTERVENTION: Cervical exploration for primary
      hyperparathyroidism or cervical mass. MAIN OUTCOME MEASURES: Age, sex, morbidity,
      imaging results, pathologic findings, cyst characteristics (size, location, and
      fluid), and perioperative calcium and parathyroid hormone levels. RESULTS: Cystic
      parathyroid lesions were found in 48 of 1769 patients (3%) studied. Functional
      parathyroid cysts were more common than NPCs, arising in 41 of 48 patients (85%),
      and showed no predisposition for sex or embryologic origin. Single-photon
      emission computed tomographic imaging failed to localize FPCs in 12 of 37
      patients (32%). The fluid in FPCs was clear or colorless in 9 of 15 characterized
      specimens (60%). Rupture of cystic parathyroid lesions during resection was
      associated with prolonged elevation of intraoperative parathyroid hormone levels
      (P =.045). Cystic parathyroid lesions weighing 4 g or more were associated with
      the development of postoperative symptomatic hypocalcemia (P =.03). Functional
      parathyroid cysts occurred exclusively in adenomas with cystic change, whereas
      NPCs (with 1 exception) were without associated adenoma on final histologic
      examination. CONCLUSIONS: Cystic parathyroid lesions often contain turbid or
      colored fluid, and FPCs are more common than NPCs. Neck cysts of uncertain origin
      should be diagnostically aspirated for parathyroid hormone content. During
      resection, cyst rupture should be avoided, and patients with large cysts should
      be managed expectantly to forestall the development of symptomatic hypocalcemia.
      Functional parathyroid cysts and NPCs are likely 2 separate clinical and
      histologic entities.

PMID- 19153326
TI  - Indication of the extent of hepatectomy for hepatocellular carcinoma on cirrhosis
      by a simple algorithm based on preoperative variables.
AB  - OBJECTIVE: To produce a model indicating the extent of hepatectomy for
      hepatocellular carcinoma on cirrhosis based on easily available preoperative
      data. DESIGN: Retrospective study based on multicenter prospectively updated
      databases. SETTING: Two tertiary referral centers specializing in hepatobiliary
      surgery. PATIENTS: A total of 466 patients undergoing hepatectomy for
      hepatocellular carcinoma on cirrhosis between 1995 and 2006. MAIN OUTCOME
      MEASURES: To create a decision tree for safe liver resection based on factors
      affecting irreversible postoperative liver failure (IPLF). RESULTS: A total of 23
      patients (4.9%) developed IPLF. The model for end-stage liver disease (MELD)
      score (categorized as <9, 9-10, and >10; P < .05 for all comparisons) and extent
      of hepatectomy were independent predictors of IPLF. In patients with a MELD score
      of less than 9, the IPLF rate was 0.4%. In patients with a MELD score of 9 or 10,
      the IPLF rate was 1.2% for resections of less than 1 segment, 5.1% for
      segmentectomies or bisegmentectomies, and 11.1% for major hepatectomies. In this
      category of MELD, serum sodium levels identified a low-risk group (sodium > or
      =140 mEq/L; to convert to millimoles per liter, multiply by 1.0) not experiencing
      IPLF and a high-risk group (sodium <140 mEq/L) in which resections of less than 1
      segment led to an IPLF rate of 2.5% and resections of 1 segment or more led to an
      IPLF rate of more than 5% (P < .05). In patients with a MELD score of more than
      10, the IPLF rate was more than 15% in all types of hepatectomies. CONCLUSION: A
      simple algorithm based on the MELD score and serum sodium level can indicate the
      maximum tolerable extent of hepatectomy for hepatocellular carcinoma on
      cirrhosis.

PMID- 19153327
TI  - Significant variations in mortality occur at similarly designated trauma centers.
AB  - HYPOTHESIS: Mortality rates vary across designated trauma centers (TC), even
      after controlling for injury severity. DESIGN: Retrospective analysis of state
      trauma registry data. SETTING: Designated Level 1 and 2 TCs in 2003 in a large
      Southwestern state. PATIENTS: Adult trauma patients (n = 18,584) treated at 15
      designated Level 1 and 2 TCs. MAIN OUTCOME MEASURES: Risk-adjusted survival was
      calculated for each trauma center using logistic regression analysis to adjust
      for differences in age, sex, race, injury mechanism, and injury severity. The
      model was developed using half of the study population and validated in the
      remaining half. It was then applied to the entire study population, with
      inclusion of TC identification codes. Observed vs Expected survival ratios were
      then calculated for each TC. Adjusted odds ratios (OR) for survival at each TC
      were also calculated. RESULTS: Adjusted OR of survival were significantly
      different from crude OR at 6 of the 14 TCs, underscoring the importance of risk
      adjustment when performing quality comparisons. One TC performed significantly
      worse than the others, 8 achieved significantly better survival, and 5 performed
      the same as the referent. Observed vs Expected ratios demonstrated that one
      trauma center had significantly worse severity-adjusted outcomes, some were
      marginal, some performed as well as expected, and none performed better than
      expectations. CONCLUSIONS: Considerable variations in risk-adjusted mortality
      rates exist across similarly designated TCs. Such variability in outcomes may
      reflect variations in quality of care, and reasons for this discrepancy should be
      explored as the next step in the trauma care quality improvement process.

PMID- 19153328
TI  - Antiplatelet agents in the perioperative period.
AB  - OBJECTIVE: To determine the use of the 3 major classes of antiplatelet drugs
      (aspirin, thienopyridines, and glycoprotein IIb/IIIa inhibitors), their
      management in the perioperative period, and the risks associated with premature
      withdrawal. DATA SOURCES: We reviewed the PubMed, EMBASE, and Cochrane databases
      using the terms antiplatelet agents in the perioperative period, antiplatelet
      agents and management of bleeding, drug-eluting stents and stent thrombosis,
      substitutes for antiplatelet agents, and premature withdrawal of antiplatelet
      agents. STUDY SELECTION: Randomized, double-blind, placebo-controlled trials;
      prospective observational studies; review articles; clinical registry data; and
      guidelines of professional bodies pertaining to antiplatelet agents were
      included. DATA EXTRACTION AND SYNTHESIS: Two researchers independently read the
      selected abstracts and selected the studies that matched the inclusion criteria.
      Any discordance between the 2 researchers was resolved by discussion so that 99
      articles were finally included. CONCLUSIONS: Aspirin use should not be stopped in
      the perioperative period unless the risk of bleeding exceeds the thrombotic risk
      from withholding the drug. With the exception of recent drug-eluting stent
      implantation, clopidogrel bisulfate use should be stopped at least 5 days prior
      to most elective surgery. Use of glycoprotein IIb/IIIa inhibitors must be
      discontinued preoperatively for more than 12 hours to allow normal hemostasis.
      Premature withdrawal of antiplatelet agents is associated with a 10% risk of all
      vascular events. Following drug-eluting stent implantation, withdrawal is
      associated with stent thrombosis and potentially fatal consequences. No
      definitive guidelines exist to manage patients who are actively bleeding while
      taking these drugs.

PMID- 19153329
TI  - The formula for a successful laparoscopic skills curriculum.
AB  - Although multiple simulators have been validated as effective training tools,
      curriculum development is lagging, and considerable work is needed to determine
      the best methods for training. This article identifies the factors that influence
      the successful incorporation of simulator training into the resident curriculum,
      reviews the evidence regarding laparoscopic curriculum development in the
      surgical literature, and provides a formula for effective curriculum design. A
      successful laparoscopic skills curriculum depends on many factors including
      participant motivation, available resources and personnel, and trainee and
      faculty commitment. It should encompass goal-oriented training, sensitive and
      objective performance metrics, appropriate methods of instruction and feedback,
      deliberate, distributed, and variable practice, an amount of overtraining,
      maintenance training, and a cognitive component. A curriculum that follows these
      principles is likely to spark trainee interest, ensure their satisfaction and
      participation in training sessions, and lead to an effective and efficient way of
      acquiring new skills using simulators. A skills curriculum is a dynamic process
      that should be tailored to individual needs and be continuously optimized based
      on accumulated evidence and experience.

PMID- 19153330
TI  - Renal transplant in HIV-positive patients: long-term outcomes and risk factors
      for graft loss.
AB  - In the highly active antiretroviral therapy era of improved survival for patients
      living with human immunodeficiency virus (HIV), chronic kidney disease now
      accounts for more than 10% of HIV-related deaths. The role of kidney transplant
      among HIV-positive patients with end-stage renal disease is under consideration,
      but concerns remain regarding allocation of kidneys to these patients when long
      term benefit has not been firmly established. We evaluated 39,501 patients
      undergoing a renal transplant between January 1, 2004, and June 30, 2006,
      identified through the United Network for Organ Sharing national registry and
      found that, although long-term allograft survival is lower among HIV-positive
      recipients, controllable risk factors may explain this disparity. With proper
      donor selection and transplant recipient management, including the avoidance of
      prolonged cold ischemic time, use of living donors, and determination of optimal
      immunosuppression dosing before transplant, long-term graft survival comparable
      to that in HIV-negative patients can be achieved.

PMID- 19153331
TI  - Image of the month. Gastrointestinal stromal tumor.

PMID- 19153332
TI  - Image of the month. Low-grade, nonfunctioning cystic pancreatic endocrine
      neoplasm.

PMID- 19153333
TI  - Futility and end-of-life organ donation after traumatic injuries: caring for
      organs or patients.

PMID- 19153334
TI  - Undertriage of elderly trauma patients to state-designated trauma centers: the
      authors' response.

PMID- 19153335
TI  - Elevation of parathyroid hormone levels in children who underwent
      parathyroidectomy for hyperparathyroidism.

PMID- 19153336
TI  - Duodenal hematoma in thrombasthenia.

PMID- 19153337
TI  - Is it truly a spontaneous duodenal hematoma?

PMID- 19153338
TI  - Treatment of epidermolysis bullosa simplex, Weber-Cockayne type, with botulinum
      toxin type A.

PMID- 19153339
TI  - Topical tretinoin therapy and all-cause mortality.
AB  - OBJECTIVE: To evaluate the relation of topical tretinoin, a commonly used
      retinoid cream, with all-cause mortality in the Veterans Affairs Topical
      Tretinoin Chemoprevention Trial (VATTC). The planned outcome of this trial was
      risk of keratinocyte carcinoma, and systemic administration of certain retinoid
      compounds has been shown to reduce risk of this cancer but has also been
      associated with increased mortality risk among smokers. DESIGN: The VATTC Trial
      was a blinded randomized chemoprevention trial, with 2- to 6-year follow-up.
      Oversight was provided by multiple independent committees. SETTING: US Department
      of Veterans Affairs medical centers. Patients A total of 1131 veterans were
      randomized. Their mean age was 71 years. Patients with a very high estimated
      short-term risk of death were excluded. Interventions Application of tretinoin,
      0.1%, or vehicle control cream twice daily to the face and ears. MAIN OUTCOME
      MEASURES: Death, which was not contemplated as an end point in the original study
      design. RESULTS: The intervention was terminated 6 months early because of an
      excessive number of deaths in the tretinoin-treated group. Post hoc analysis of
      this difference revealed minor imbalances in age, comorbidity, and smoking
      status, all of which were important predictors of death. After adjusting for
      these imbalances, the difference in mortality between the randomized groups
      remained statistically significant. CONCLUSIONS: We observed an association of
      topical tretinoin therapy with death, but we do not infer a causal association
      that current evidence suggests is unlikely.

PMID- 19153340
TI  - Estrogen receptor expression in cutaneous melanoma: a real-time reverse
      transcriptase-polymerase chain reaction and immunohistochemical study.
AB  - OBJECTIVE: To evaluate estrogen receptor (ER) expression in human melanoma
      tissues and in the adjacent healthy skin with the aim of explaining whether the
      ERalpha:ERbeta expression ratio has a role in neoplastic progression. DESIGN:
      Prospective study. SETTING: Department of Dermatology, University of Florence,
      Florence, Italy. Patients Fourteen patients, 12 with cutaneous melanoma (6 women
      and 6 men) and 2 with melanocytic nevi (1 woman and 1 man). MAIN OUTCOME
      MEASURES: Using quantitative reverse transcriptase-polymerase chain reaction and
      immunohistochemical analysis, we analyzed ERalpha and ERbeta messenger RNA (mRNA)
      and ERbeta protein expression in cutaneous melanoma and in the healthy skin
      surrounding the lesions. RESULTS: All melanocytic lesions expressed detectable
      levels of ERalpha and ERbeta mRNA as well as ERbeta protein. Dividing melanoma
      cases into 2 groups according to Breslow thickness, we found lower ERalpha and
      ERbeta mRNA levels and lower ERbeta protein levels in thicker, more invasive
      tumors. CONCLUSIONS: These observations suggest a role for ERs in the metastatic
      process of melanoma cells, pointing at the possibility of using ERbeta expression
      as a prognostic indicator of melanoma. The possibility of distinguishing
      proliferative melanomas, which are associated with dismal prognosis, from the so
      called dormant melanomas opens up novel avenues in tailoring individual
      treatments, as already happens for other tumors.

PMID- 19153341
TI  - Non-sexually related acute genital ulcers in 13 pubertal girls: a clinical and
      microbiological study.
AB  - OBJECTIVE: To describe the clinical and microbiological features of acute genital
      ulcers (AGU), which have been reported in virgin adolescents, predominantly in
      girls. DESIGN: Descriptive study. We collected data on the clinical features,
      sexual history, blood cell count, biochemistry, microbiological workup, and 1
      year follow-up. SETTING: Departments of dermatology of 3 university hospitals in
      Paris. Patients Thirteen immunocompetent female patients with a first flare of
      non-sexually transmitted AGU. MAIN OUTCOME MEASURES: Clinical and microbiological
      data, using a standardized form. RESULTS: Mean age was 16.6 years (range, 11-19
      years). Eleven patients denied previous sexual contact. A fever or flulike
      symptoms preceded AGU in 10 of the 13 patients (77%), with a mean delay of 3.8
      days before the AGU onset (range, 0-10 days). The genital ulcers were bilateral
      in 10 patients. The final diagnosis was Epstein-Barr virus primary infection in 4
      patients (31%) and Behcet disease in 1 patient (8%). No other infectious agents
      were detected in this series. CONCLUSIONS: We recommend serologic testing for
      Epstein-Barr virus with IgM antibodies to viral capsid antigens in non-sexually
      related AGU in immunocompetent patients. Further microbiological studies are
      required to identify other causative agents.

PMID- 19153342
TI  - The role of online support communities: benefits of expanded social networks to
      patients with psoriasis.
AB  - OBJECTIVE: To determine the demographics, usage patterns, attitudes, and
      experiences of online support site users. DESIGN: Online survey. Patients A total
      of 260 subjects recruited from 5 online psoriasis support groups. MAIN OUTCOME
      MEASURES: An exploratory analysis was performed to determine demographic and
      disease characteristics of online support site users. Perceived benefits were
      also documented. RESULTS: The mean (SD) age of respondents was 40.1 (11.5) years
      (range, 18-75 years), most (75.7%) were white, female (60.4%), and college
      educated (84.3%). Key factors associated with use of online support sites
      included availability of resources (95.3%), convenience (94.0%), access to good
      advice (91.0%), and the lack of embarrassment when dealing with personal issues
      (90.8%). The most common activities were posting messages (65.0%) and searching
      for information (63.1%). Nearly half of all respondents perceived improvements in
      their quality of life (49.5%) and psoriasis severity (41.0%) since joining the
      site. Intensity of participation in online support activities was associated with
      improved quality of life (P = .002), but not with improvements in psoriasis
      severity. CONCLUSIONS: Our data demonstrate that psoriasis virtual communities
      offer users both a valuable educational resource and a source of psychological
      and social support. Such benefits could be further enhanced by physician
      engagement within these communities.

PMID- 19153343
TI  - Subcutaneous trigger point causing radiating postsurgical pain.
AB  - BACKGROUND: The immediate onset of severe postoperative pain, especially pain
      radiating distant from the incision site, is uncommon after dermatologic surgery.
      OBSERVATION: A 37-year-old woman undergoing excision of a nevus from the left
      side of her midback had an exquisitely tender spot along the incision lines. This
      tender spot was hard to anesthetize and was clinically visible, after excision of
      the nevus, as a fibrous bundle in the subcutaneous plane. She presented in the
      immediate postoperative period with referred (distant) pain extending down the
      ipsilateral arm that was caused by a thoracic subcutaneous trigger point.
      CONCLUSION: Surgeons and pain management specialists should be aware of this
      potential cause of immediate postoperative pain to prevent unnecessary medical or
      surgical interventions in the postoperative period.

PMID- 19153344
TI  - Relation between animal-type melanoma and reduced nuclear expression of
      glutathione S-transferase pi.
AB  - BACKGROUND: Animal-type melanoma (ATM) is a rare variant of the tumor showing
      diffuse, heavily pigmented neoplastic cells in the dermis. Despite the high mean
      thickness of the lesions, reports seem to indicate a less aggressive behavior and
      a better survival rate for ATM compared with conventional melanoma, but the
      underlying pathways related to this favorable outcome are still unknown.
      OBSERVATIONS: Five women and 2 men aged 20 to 92 years presented with pigmented
      skin nodules (n = 5) or plaques (n = 2), varying in size from 1.0 to 4.5 cm.
      Findings from microscopic examination showed monotypic-appearing melanocytes with
      abundant intracytoplasmic melanin in a nodular or fascicular arrangement (mean
      Breslow thickness, 4.97 mm). Immunohistochemical analysis of ATM cells
      demonstrated the typical positive staining for S-100, vimentin, HMB-45, and melan
      A. The investigation of the pi isoform of glutathione S-transferase, a family of
      enzymes involved in tumor progression, revealed that nuclear expression is
      reduced in ATMs compared with control melanomas, whereas results from cytoplasmic
      staining did not vary. One patient died of cardiac failure without evidence of
      disease progression; the remaining patients are disease-free at 3 (n = 4) and 5
      years (n = 3). CONCLUSIONS: Our findings confirm that ATM is a variant of
      melanoma with distinctive clinical and histological features. Low nuclear
      expression of glutathione S-transferase pi expression is a characteristic of ATM
      and could add new insight to better understand the unusual biological behavior of
      this rare neoplasm.

PMID- 19153345
TI  - Minocycline-induced drug hypersensitivity syndrome followed by multiple
      autoimmune sequelae.
AB  - BACKGROUND: Drug hypersensitivity syndrome (DHS) is a severe, multisystem adverse
      drug reaction that may occur following the use of numerous medications, including
      anticonvulsants, sulfonamides, and minocycline hydrochloride. Long-term
      autoimmune sequelae of DHS have been reported, including hypothyroidism.
      OBSERVATIONS: A 15-year-old female adolescent developed DHS 4 weeks after
      starting minocycline therapy for acne vulgaris. Seven weeks later she developed
      autoimmune hyperthyroidism (Graves disease), and 7 months after discontinuing
      minocycline therapy she developed autoimmune type 1 diabetes mellitus. In
      addition, she developed elevated titers of several markers of systemic autoimmune
      disease, including antinuclear, anti-Sjogren syndrome A, and anti-Smith
      antibodies. CONCLUSIONS: Minocycline-associated DHS may be associated with
      multiple autoimmune sequelae, including thyroid disease, type 1 diabetes
      mellitus, and elevated markers of systemic autoimmunity. Long-term follow-up is
      needed in patients with DHS to determine the natural history of DHS-associated
      sequelae.

PMID- 19153346
TI  - Twelve-year analysis of severe cases of drug reaction with eosinophilia and
      systemic symptoms: a cause of unpredictable multiorgan failure.
AB  - BACKGROUND: Factors implicated in the severity of drug reaction with eosinophilia
      and systemic symptoms (DRESS) have not been identified. We retrospectively
      describe and analyze severe cases of DRESS defined by history of intensive care
      unit admission and death due to DRESS. OBSERVATIONS: Of 15 patients
      retrospectively recruited in France, 14 were admitted to the intensive care unit
      and 3 died. The culprit drugs were already known to cause or trigger DRESS:
      allopurinol, minocycline hydrochloride, anticonvulsants, sulfonamides, and
      antibiotics. Visceral involvement with severe manifestations responsible for
      intensive care unit admission or death was variable and often multiple
      (pneumonitis, hepatitis, renal failure, encephalitis, hemophagocytosis, cardiac
      failure, and pancytopenia) and resulted in multiorgan failure in 11 patients.
      These severe complications sometimes developed late in DRESS. Human herpesvirus 6
      infection was demonstrated in 6 of 7 patients. In addition, human herpesvirus 6
      infection was demonstrated in involved viscera in 2 patients. CONCLUSIONS: Severe
      DRESS is rare. Some specificities of visceral involvement were associated with
      allopurinol and minocycline. However, visceral involvement comprising multiorgan
      failure seemed to be unpredictable. Better knowledge of DRESS is necessary to
      propose specific and prompt treatment. Early demonstration of human herpesvirus 6
      reactivation could be considered a prognostic factor for identifying patients at
      higher risk and, hence, needs to be evaluated.

PMID- 19153347
TI  - Estrogen receptor expression in cutaneous melanoma.

PMID- 19153349
TI  - Subcutaneous nodules in an infant. Neuroblastoma.

PMID- 19153348
TI  - Dealing with unanticipated mortality in a large randomized clinical trial of
      topical tretinoin.

PMID- 19153350
TI  - Asymptomatic, edematous upper lip in a 39-year-old woman. Cheilitis granulomatosa
      (CG).

PMID- 19153351
TI  - Acral atrophic papules, petechia, and patches of alopecia. Syringotropic mycosis
      fungoides (MF).

PMID- 19153352
TI  - Erythematous papules on the legs. IgM storage papules in association with WM.

PMID- 19153353
TI  - The antibacterial activity of clove essential oil against Propionibacterium acnes
      and its mechanism of action.

PMID- 19153354
TI  - Long-term maintenance of a successful occupational sun safety intervention.

PMID- 19153355
TI  - Lymphangiogenesis induced by surgery: a risk for melanoma metastasis.

PMID- 19153356
TI  - Truncal pruritic papular eruption and palmar hyperhidrosis after spinal cord
      contusion.

PMID- 19153357
TI  - Clinical and dermoscopic features of porokeratosis of Mibelli.

PMID- 19153358
TI  - Progression of undiagnosed cutaneous T-cell lymphoma during efalizumab therapy.

PMID- 19153359
TI  - Exacerbation of undiagnosed mycosis fungoides during treatment with etanercept.

PMID- 19153360
TI  - Severe symptomatic hypocalcemia in a patient with RDEB treated with intravenous
      zoledronic acid.

PMID- 19153361
TI  - Necrotizing soft-tissue infection caused by both Candida glabrata and
      Streptococcus agalactiae.

PMID- 19153362
TI  - Limited cutaneous systemic sclerosis induced by paclitaxel in a patient with
      breast cancer.

PMID- 19153363
TI  - Lipoatrophy associated with interferon alfa adjuvant therapy for melanoma.

PMID- 19153364
TI  - Pityriasis rubra pilaris responding rapidly to adalimumab.

PMID- 19153365
TI  - When Galeni met Paracelsus: a paleodermatological case of luetic gumma care.

PMID- 19153366
TI  - skINsight lessons in reflectance confocal microscopy: rapid diagnosis of
      pigmented basal cell carcinoma.

PMID- 19153367
TI  - Clinical reasoning: a case of Wegener granulomatosis complicated by seizures and
      headaches: curiouser and curiouser.

PMID- 19153369
TI  - Seizures and arrhythmias: Differing phenotypes of a common channelopathy?

PMID- 19153370
TI  - Incidence of acquired demyelination of the CNS in Canadian children.
AB  - BACKGROUND: The incidence of acquired demyelination of the CNS (acquired
      demyelinating syndromes [ADS]) in children is unknown. It is important that
      physicians recognize the features of ADS to facilitate care and to appreciate the
      future risk of multiple sclerosis (MS). OBJECTIVE: To determine the incidence,
      clinical features, familial autoimmune history, and acute management of Canadian
      children with ADS. METHODS: Incidence and case-specific data were obtained
      through the Canadian Pediatric Surveillance Program from April 1, 2004, to March
      31, 2007. Before study initiation, a survey was sent to all pediatric health care
      providers to determine awareness of MS as a potential outcome of ADS in children.
      RESULTS: Two hundred nineteen children with ADS (mean age 10.5 years, range 0.66
      18.0 years; female to male ratio 1.09:1) were reported. The most common
      presentations were optic neuritis (ON; n = 51, 23%), acute disseminated
      encephalomyelitis (ADEM; n = 49, 22%), and transverse myelitis (TM; n = 48, 22%).
      Children with ADEM were more likely to be younger than 10 years, whereas children
      with monolesional ADS (ON, TM, other) were more likely to be older than 10 years
      (p < 0.001). There were 73 incident cases per year, leading to an annual
      incidence of 0.9 per 100,000 Canadian children. A family history of MS was
      reported in 8%. Before study initiation, 65% of physicians indicated that they
      considered MS as a possible outcome of ADS in children. This increased to 74% in
      year 1, 81% in year 2, and 87% in year 3. CONCLUSION: The incidence of pediatric
      acquired demyelinating syndromes (ADS) is 0.9 per 100,000 Canadian children. ADS
      presentations are influenced by age.

PMID- 19153371
TI  - X-linked distal hereditary motor neuropathy maps to the DSMAX locus on chromosome
      Xq13.1-q21.
AB  - OBJECTIVE: To clinically characterize and map the gene locus in a three
      generation family with an X-linked adult-onset distal hereditary motor
      neuropathy. METHODS: Microsatellite markers spanning the juvenile distal spinal
      muscular atrophy (DSMAX) locus were genotyped and analyzed using genetic linkage
      analysis. The promoter, untranslated and coding region of the gap junction beta1
      (GJB1) gene was sequenced. Nine positional candidate genes were screened for
      disease mutations using high-resolution melt (HRM) analysis. RESULTS: The family
      showed significant linkage to markers on chromosome Xq13.1-q21. Haplotype
      construction revealed a disease-associated haplotype between the markers DXS991
      and DX5990. Sequence analysis excluded pathogenic changes in the coding and
      promoter regions of the GJB1 gene. Additional fine mapping in the family refined
      the DSMAX locus to a 1.44-cM interval between DXS8046 and DXS8114. HRM analysis
      did not identify disease-associated mutations in the coding region of nine
      candidate genes. CONCLUSION: We have identified a family with adult-onset distal
      hereditary motor neuropathy that refines the locus reported for juvenile distal
      spinal muscular atrophy (DSMAX) on chromosome Xq13.1-q21. Exclusion of mutations
      in the coding and regulatory region of the GJB1 gene eliminated the CMTX1 locus
      as a cause of disease in this family. Nine positional candidate genes in the
      refined interval underwent mutation analysis and were eliminated as the
      pathogenic cause of DSMAX in this family. The syndrome in this family may be
      allelic to the juvenile distal spinal muscular atrophy first reported at this
      locus.

PMID- 19153372
TI  - Personality and lifestyle in relation to dementia incidence.
AB  - OBJECTIVE: High neuroticism has been associated with a greater risk of dementia,
      and an active/socially integrated lifestyle with a lower risk of dementia. The
      aim of the current study was to explore the separate and combined effects of
      neuroticism and extraversion on the risk of dementia, and to examine whether
      lifestyle factors may modify this association. METHODS: A population-based cohort
      of 506 older people with no dementia from the Kungsholmen Project, Stockholm,
      Sweden, was followed up for an average of 6 years. Personality traits were
      assessed using the Eysenck Personality Inventory. Dementia was diagnosed by
      specialists according to DSM-III-R criteria. RESULTS: Neither high neuroticism
      nor low extraversion alone was related to significantly higher incidence of
      dementia. However, among people with an inactive or socially isolated lifestyle,
      low neuroticism was associated with a decreased dementia risk (hazard ratio [HR]
      = 0.51, 95% confidence interval [CI] = 0.27-0.96). When compared to persons with
      high neuroticism and high extraversion, a decreased risk of dementia was detected
      in individuals with low neuroticism and high extraversion (HR = 0.51, 95% CI =
      0.28-0.94), but not among persons with low neuroticism and low extraversion (HR =
      0.95, 95% CI = 0.57-1.60), nor high neuroticism and low extraversion (HR = 0.97
      95% CI = 0.57-1.65). Stratified analysis by lifestyle showed that the inverse
      association of low neuroticism and high extraversion in combination was present
      only among the inactive or socially isolated persons. CONCLUSION: Low neuroticism
      in combination with high extraversion is the personality trait associated with
      the lowest dementia risk; however, among socially isolated individuals even low
      neuroticism alone seems to decrease dementia risk.

PMID- 19153373
TI  - Autosomal dominant subcortical gliosis presenting as frontotemporal dementia.
AB  - OBJECTIVE: To describe a multigenerational kindred with a frontotemporal dementia
      clinical syndrome (FTDS), extensive subcortical gliosis pathology, and autosomal
      dominant genetics. METHODS: Clinical, imaging, and pathologic evaluations of
      multiple family members. RESULTS: Symptom onset commonly occurred in the fifth or
      sixth decade, although some kindred members did not develop obvious symptoms
      until their eighth decade. White matter changes were prominent on both MRI and CT
      imaging. Results from six brain autopsy evaluations showed consistent but varying
      degrees of pathology that, while unique, share some histologic similarities with
      leukodystrophies. These brains were notably devoid of both tau- and ubiquitin
      containing inclusions. CONCLUSIONS: Subcortical gliosis in this kindred arises
      from mutation of a novel gene or else represents a unique frontotemporal dementia
      clinical syndrome variant caused by mutation of an already known gene. Clinical
      relevance and research implications are discussed.

PMID- 19153375
TI  - Genetics of epilepsy syndromes starting in the first year of life.
AB  - BACKGROUND: Incidence rates of epilepsy in children are highest during the first
      year of life. Most frequently, epilepsy results from a metabolic or structural
      defect in the brain. However, some infants have clearly delineated epilepsy
      syndromes for which no underlying etiology can be identified except for a genetic
      predisposition. METHODS: We reviewed the current knowledge on the genetics of
      epilepsy syndromes starting in the first year of life. We focus on those epilepsy
      syndromes without a clear structural or metabolic etiology. RESULTS: Recent
      molecular studies have led to the identification of the responsible gene defects
      for several of the monogenetic epilepsy syndromes with onset in the first year of
      life. DISCUSSION: This knowledge has consequences for clinical practice as it
      opens new perspectives for genetic testing, improving early diagnosis, and
      facilitating genetic counseling. This overview of epilepsy syndromes and
      associated gene defects might serve as a basis for the selection of patients in
      whom genetic testing can be helpful.

PMID- 19153374
TI  - Plasma Abeta, homocysteine, and cognition: the Vitamin Intervention for Stroke
      Prevention (VISP) trial.
AB  - BACKGROUND: Amyloid-beta protein (Abeta) plays a key role in Alzheimer disease
      (AD) and is also implicated in cerebral small vessel disease. Serum total
      homocysteine (tHcy) is a risk factor for small vessel disease and cognitive
      impairment and correlates with plasma Abeta levels. To determine whether this
      association results from a common pathophysiologic mechanism, we investigated
      whether vitamin supplementation-induced reduction of tHcy influences plasma Abeta
      levels in the Vitamin Intervention in Stroke Prevention (VISP) study. METHODS:
      Two groups of 150 patients treated with either the high-dose or low-dose
      formulation of pyridoxine, cobalamin, and folic acid in a randomized, double
      blind fashion were selected among the participants in the VISP study without
      recurrent stroke during follow-up and in the highest 10% of the distribution for
      baseline tHcy levels. Concentrations of plasma Abeta with 40 (Abeta40) and 42
      (Abeta42) amino acids were measured at baseline and at the 2-year visit. RESULTS:
      tHcy levels significantly decreased with vitamin supplementation in both groups.
      tHcy were strongly correlated with Abeta40 but not Abeta42 concentrations. There
      was no difference in the change in Abeta40, Abeta42 (p = 0.40, p = 0.35), or the
      Abeta42/Abeta40 ratio over time (p = 0.86) between treatment groups. Abeta
      measures were not associated with cognitive change. CONCLUSIONS: This double
      blind randomized controlled trial of vitamin therapy demonstrates a strong
      correlation between serum tHcy and plasma Abeta40 concentrations in subjects with
      ischemic stroke. Treatment with high dose vitamins does not, however, influence
      plasma levels of Abeta, despite their effect on lowering tHcy. Our results
      suggest that although tHcy is associated with plasma Abeta40, they may be
      regulated by independent mechanisms.

PMID- 19153376
TI  - Gamma-hydroxybutyric acid and its relevance in neurology.

PMID- 19153377
TI  - A case of ALS-FTD in a large FALS pedigree with a K17I ANG mutation.

PMID- 19153378
TI  - Inflammatory pseudotumor associated with HIV, JCV, and immune reconstitution
      syndrome.

PMID- 19153379
TI  - Ocular flutter as the first manifestation of Lyme disease.

PMID- 19153380
TI  - Intranasal insulin improves cognition and modulates beta-amyloid in early AD.

PMID- 19153381
TI  - Transmissible spongiform encephalopathy in the 21st Century: neuroscience for the
      clinical neurologist.

PMID- 19153382
TI  - Voluntary partial retraction of: Recessive inheritance and variable penetrance of
      slow-channel congenital myasthenic syndromes.

PMID- 19153384
TI  - Obama and the opportunity to eliminate nuclear weapons.

PMID- 19153385
TI  - Defining and disseminating the hospital-at-home model.

PMID- 19153386
TI  - Doctors crossing borders: Europe's new reality.

PMID- 19153387
TI  - Colour-coded wristbands confusing.

PMID- 19153388
TI  - Alternative isotope sources.

PMID- 19153390
TI  - Perfect predilections.

PMID- 19153391
TI  - Research foundations tight-lipped about investment losses.

PMID- 19153392
TI  - Hard hearts and horse-drawn carts.

PMID- 19153393
TI  - Irish eyes smiling as dispensing fees are lifted.

PMID- 19153394
TI  - Avoiding hospital admission through provision of hospital care at home: a
      systematic review and meta-analysis of individual patient data.
AB  - BACKGROUND: Avoidance of admission through provision of hospital care at home is
      a scheme whereby health care professionals provide active treatment in the
      patient's home for a condition that would otherwise require inpatient treatment
      in an acute care hospital. We sought to compare the effectiveness of this method
      of caring for patients with that type of in-hospital care. METHODS: We searched
      the MEDLINE, EMBASE, CINAHL and EconLit databases and the Cochrane Effective
      Practice and Organisation of Care Group register from the earliest date in each
      database until January 2008. We included randomized controlled trials that
      evaluated a service providing an alternative to admission to an acute care
      hospital. We excluded trials in which the program did not offer a substitute for
      inpatient care. We performed meta-analyses for trials for which the study
      populations had similar characteristics and for which common outcomes had been
      measured. RESULTS: We included 10 randomized trials (with a total of 1327
      patients) in our systematic review. Seven of these trials (with a total of 969
      patients) were deemed eligible for meta-analysis of individual patient data, but
      we were able to obtain data for only 5 of these trials (with a total of 844
      patients [87%]). There was no significant difference in mortality at 3 months for
      patients who received hospital care at home (adjusted hazard ratio [HR] 0.77, 95%
      confidence interval [CI] 0.54-1.09, p = 0.15). However, at 6 months, mortality
      was significantly lower for these patients (adjusted HR 0.62, 95% CI 0.45-0.87, p
      = 0.005). Admissions to hospital were greater, but not significantly so, for
      patients receiving hospital care at home (adjusted HR 1.49, 95% CI 0.96-2.33, p =
      0.08). Patients receiving hospital care at home reported greater satisfaction
      than those receiving inpatient care. These programs were less expensive than
      admission to an acute care hospital ward when the analysis was restricted to
      treatment actually received and when the costs of informal care were excluded.
      INTERPRETATION: For selected patients, avoiding admission through provision of
      hospital care at home yielded similar outcomes to inpatient care, at a similar or
      lower cost.

PMID- 19153395
TI  - Hepatitis B immunization strategies: timing is everything.

PMID- 19153396
TI  - A patient with loss of vision in the right eye and neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 is a common autosomal dominant condition that affects
      about 1 in 5000 people. We describe a 75-year-old man who, in addition to many
      classic developmental changes of the disease in his skin, eyes and nervous
      system, had blindness in his right eye as a complication.

PMID- 19153398
TI  - Information exchange between provider and patient.

PMID- 19153399
TI  - Quieten your inner critic.

PMID- 19153403
TI  - Discoloration of skin and urine after treatment with hydroxocobalamin for cyanide
      poisoning.

PMID- 19153404
TI  - The overnight smackdown: avoiding on-call arguments.

PMID- 19153405
TI  - Agranulocytosis after consumption of cocaine adulterated with levamisole.

PMID- 19153406
TI  - QTc interval screening in methadone treatment.
AB  - DESCRIPTION: An independent panel developed cardiac safety recommendations for
      physicians prescribing methadone. METHODS: Expert panel members reviewed and
      discussed the following sources regarding methadone: pertinent English-language
      literature identified from MEDLINE and EMBASE searches (1966 to June 2008),
      national substance abuse guidelines from the United States and other countries,
      information from regulatory authorities, and physician awareness of adverse
      cardiac effects. RECOMMENDATION 1 (DISCLOSURE): Clinicians should inform patients
      of arrhythmia risk when they prescribe methadone. RECOMMENDATION 2 (CLINICAL
      HISTORY): Clinicians should ask patients about any history of structural heart
      disease, arrhythmia, and syncope. RECOMMENDATION 3 (SCREENING): Obtain a
      pretreatment electrocardiogram for all patients to measure the QTc interval and a
      follow-up electrocardiogram within 30 days and annually. Additional
      electrocardiography is recommended if the methadone dosage exceeds 100 mg/d or if
      patients have unexplained syncope or seizures. RECOMMENDATION 4 (RISK
      STRATIFICATION): If the QTc interval is greater than 450 ms but less than 500 ms,
      discuss the potential risks and benefits with patients and monitor them more
      frequently. If the QTc interval exceeds 500 ms, consider discontinuing or
      reducing the methadone dose; eliminating contributing factors, such as drugs that
      promote hypokalemia; or using an alternative therapy. RECOMMENDATION 5 (DRUG
      INTERACTIONS): Clinicians should be aware of interactions between methadone and
      other drugs that possess QT interval-prolonging properties or slow the
      elimination of methadone.

PMID- 19153407
TI  - Summaries for patients. QTc interval screening in methadone treatment.

PMID- 19153408
TI  - Summaries for patients. Does measuring genetic variations at chromosome 9p21.3
      help to predict cardiovascular disease in women?

PMID- 19153409
TI  - Cardiovascular disease risk prediction with and without knowledge of genetic
      variation at chromosome 9p21.3.
AB  - BACKGROUND: Although genetic variation at chromosome 9p21.3 is associated with
      incident cardiovascular disease, it is unclear whether screening for this
      polymorphism improves risk prediction. OBJECTIVE: To determine whether knowledge
      of variation at chromosome 9p21.3 provides predictive information beyond that
      from other readily available risk factors. DESIGN: Prospective cohort study.
      SETTING: United States. PATIENTS: 22 129 female white health professionals
      participating in the Women's Genome Health Study, initially without any major
      chronic disease, who were prospectively followed over a median of 10.2 years for
      incident cardiovascular disease. MEASUREMENTS: Polymorphism at rs10757274 in
      chromosome 9p21.3 and additional cardiovascular disease risk factors (blood
      pressure, smoking status, diabetes, blood levels of cholesterol, high-sensitivity
      C-reactive protein, and family history of premature myocardial infarction).
      RESULTS: Polymorphism at rs10757274 was associated with an adjusted hazard ratio
      for incident cardiovascular disease of 1.25 (95% CI, 1.04 to 1.51) for the AG
      genotype and 1.32 (CI, 1.07 to 1.63) for the GG genotype. However, the addition
      of the genotype to a prediction model based on traditional risk factors, high
      sensitivity C-reactive protein, and family history of premature myocardial
      infarction had no effect on model discrimination as measured by the c-index
      (0.807 to 0.809) and did not improve the Net Reclassification Improvement score (
      0.2%; P = 0.59) or the Integrated Discrimination Improvement score (0.0; P =
      0.18). LIMITATION: Study participants were all white women. CONCLUSION: In this
      large prospective cohort of white women, genetic variation in chromosome 9p21.3
      was associated with incident cardiovascular disease but did not improve on the
      discrimination or classification of predicted risk achieved with traditional risk
      factors, high-sensitivity C-reactive protein, and family history of premature
      myocardial infarction.

PMID- 19153410
TI  - Cost-effectiveness of using pharmacogenetic information in warfarin dosing for
      patients with nonvalvular atrial fibrillation.
AB  - BACKGROUND: Variants in genes involved in warfarin metabolism and sensitivity
      affect individual warfarin requirements and the risk for bleeding. Testing for
      these variant alleles might allow more personalized dosing of warfarin during the
      induction phase. In 2007, the U.S. Food and Drug Administration changed the
      labeling for warfarin (Coumadin, Bristol-Myers Squibb, Princeton, New Jersey),
      suggesting that clinicians consider genetic testing before initiating therapy.
      OBJECTIVE: To examine the cost-effectiveness of genotype-guided dosing versus
      standard induction of warfarin therapy for patients with nonvalvular atrial
      fibrillation. DESIGN: Markov state transition decision model. DATA SOURCES:
      MEDLINE searches and bibliographies from relevant articles of literature
      published in English. TARGET POPULATION: Outpatients or inpatients requiring
      initiation of warfarin therapy. The base case was a man age 69 years with newly
      diagnosed nonvalvular atrial fibrillation and no contraindications to warfarin
      therapy. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Genotype
      guided dosing consisting of genotyping for CYP2C9*2, CYP2C9*3, and/or VKORC1
      versus standard warfarin induction. OUTCOME MEASURES: Effectiveness was measured
      in quality-adjusted life-years (QALYs), and costs were in 2007 U.S. dollars.
      RESULTS: In the base case, genotype-guided dosing resulted in better outcomes,
      but at a relatively high cost. Overall, the marginal cost-effectiveness of
      testing exceeded $170 000 per QALY. On the basis of current data and cost of
      testing (about $400), there is only a 10% chance that genotype-guided dosing is
      likely to be cost-effective (that is, <$50 000 per QALY). Sensitivity analyses
      revealed that for genetic testing to cost less than $50 000 per QALY, it would
      have to be restricted to patients at high risk for hemorrhage or meet the
      following optimistic criteria: prevent greater than 32% of major bleeding events,
      be available within 24 hours, and cost less than $200. LIMITATION: Few published
      studies describe the effect of genotype-guided dosing on major bleeding events,
      and although these studies show a trend toward decreased bleeding, the results
      are not statistically significant. CONCLUSION: Warfarin-related genotyping is
      unlikely to be cost-effective for typical patients with nonvalvular atrial
      fibrillation, but may be cost-effective in patients at high risk for hemorrhage
      who are starting warfarin therapy.

PMID- 19153411
TI  - High-density lipoprotein particle size and concentration and coronary risk.
AB  - BACKGROUND: High-density lipoprotein (HDL) cholesterol levels are inversely
      related to risk for coronary artery disease (CAD). Because HDL particles are
      heterogeneous in size and composition, they may be differentially associated with
      other cardiovascular risk factors and with cardiovascular risk. OBJECTIVE: To
      study the independent relationships of HDL size and particle concentration to
      risk for future CAD. DESIGN: Nested case-control study within the EPIC (European
      Prospective Investigation into Cancer and Nutrition)-Norfolk cohort; baseline
      survey between 1993 and 1997, follow-up until November 2003. SETTING: Norfolk,
      United Kingdom. PARTICIPANTS: Case patients were 822 apparently healthy men and
      women who developed CAD during follow-up. Control participants were 1401
      participants who remained without CAD and were matched to case patients by sex,
      age, and enrollment time. MEASUREMENTS: First CAD event leading to either
      hospitalization or death. RESULTS: Nuclear magnetic resonance spectroscopy
      measured HDL particle concentration (mean, 33.9 micromol/L [SD, 5] vs. 32.9
      micromol/L [SD, 6]; P < 0.001) and HDL size (mean, 8.9 nm [SD, 0.5] vs. 8.8 nm
      [SD, 0.5]; P < 0.001), as well as gradient gel electrophoresis-measured HDL size
      (mean, 8.9 nm [SD, 0.4] vs. 8.8 nm [SD, 0.4]; P = 0.005) were lower in case
      patients than in control participants. High-density lipoprotein size and HDL
      particle concentration were only weakly correlated (r = 0.08, for those measured
      with nuclear magnetic resonance spectroscopy; r = 0.10, for those measured with
      gradient gel electrophoresis). High-density lipoprotein size was strongly
      associated with risk factors characteristic of the metabolic syndrome, including
      waist-to-hip ratio, triglyceride level, and apolipoprotein B level, whereas HDL
      particle concentration was not. Both HDL size and HDL particle concentration were
      independently associated with CAD risk. The association between HDL size and CAD
      risk was abolished on adjustment for apolipoprotein B and triglyceride levels
      (adjusted odds ratio, 1.00 [95% CI, 0.71 to 1.39] for top vs. bottom quartile),
      whereas HDL particle concentration remained independently associated with CAD
      risk (adjusted odds ratio, 0.50 [CI, 0.37 to 0.66]). LIMITATION: Measurements
      were performed in nonfasting blood samples, and residual confounding cannot be
      excluded. CONCLUSION: Both HDL size and HDL particle concentration were
      independently associated with other cardiovascular risk factors and with the risk
      for CAD. The relationship between HDL size and CAD risk was explained by markers
      associated with the metabolic syndrome, indicating that part of the relationship
      between HDL cholesterol and CAD risk is merely a reflection of this metabolic
      risk.

PMID- 19153412
TI  - Narrative review: effect of bariatric surgery on type 2 diabetes mellitus.
AB  - Bariatric surgery leads to substantial and durable weight reduction. Nearly 30%
      of patients who undergo bariatric surgery have type 2 diabetes, and for many of
      them, diabetes resolves after surgery (84% to 98% for bypass procedures and 48%
      to 68% for restrictive procedures). Glycemic control improves in part because of
      caloric restriction but also because gut peptide secretion changes. Gut peptides,
      which mediate the enteroinsular axis, include the incretins glucagon-like peptide
      1 and glucose-dependent insulinotropic peptide, as well as ghrelin and peptide
      YY. Bariatric surgery (particularly bypass procedures) alters secretion of these
      gut hormones, which results in enhanced insulin secretion and sensitivity. This
      review discusses the various bariatric procedures and how they alter the
      enteroinsular axis. Familiarity with these effects can help physicians decide
      among the different surgical procedures and avoid postoperative hypoglycemia.

PMID- 19153413
TI  - Who should receive life support during a public health emergency? Using ethical
      principles to improve allocation decisions.
AB  - A public health emergency, such as an influenza pandemic, will lead to shortages
      of mechanical ventilators, critical care beds, and other potentially life-saving
      treatments. Difficult decisions about who will and will not receive these scarce
      resources will have to be made. Existing recommendations reflect a narrow
      utilitarian perspective, in which allocation decisions are based primarily on
      patients' chances of survival to hospital discharge. Certain patient groups, such
      as the elderly and those with functional impairment, are denied access to
      potentially life-saving treatments on the basis of additional allocation
      criteria. We analyze the ethical principles that could guide allocation and
      propose an allocation strategy that incorporates and balances multiple morally
      relevant considerations, including saving the most lives, maximizing the number
      of "life-years" saved, and prioritizing patients who have had the least chance to
      live through life's stages. We also argue that these principles are relevant to
      all patients and therefore should be applied to all patients, rather than
      selectively to the elderly, those with functional impairment, and those with
      certain chronic conditions. We discuss strategies to engage the public in setting
      the priorities that will guide allocation of scarce life-sustaining treatments
      during a public health emergency.

PMID- 19153414
TI  - Personalized genetic prediction: too limited, too expensive, or too soon?

PMID- 19153415
TI  - Preparation.

PMID- 19153416
TI  - Could performance-enhancing drugs be responsible for small pituitary volume in
      retired boxers?

PMID- 19153417
TI  - The first use of penicillin in the United States.

PMID- 19153418
TI  - The first use of penicillin in the United States.

PMID- 19153419
TI  - The rise of the term "prehypertension".

PMID- 19153420
TI  - Does furosemide have a role in the management of hypercalcemia?

PMID- 19153421
TI  - The first use of penicillin in the United States.

PMID- 19153422
TI  - First case report of community-acquired pneumonia due to Tsukamurella pulmonis.

PMID- 19153423
TI  - Will all health care reform lead back to Medicaid?

PMID- 19153424
TI  - Factors associated with bone metastasis in breast cancer: a preliminary study in
      an Indonesian population.
AB  - AIM: to know the characteristics of breast cancer patients with bone metastasis
      and its risk factors. METHODS: this was a cross-sectional study on breast cancer
      patients in Dharmais Cancer Hospital between 1998 and 2002. Data were retrieved
      from medical records and consisted of age, history of hormonal contraceptive use,
      histopathological type, estrogen receptor (ER) and progesteron receptor (PR)
      expression, c-erbB-2 and cathepsin D expressions. RESULTS: a total of 197 cases
      were recruited between the study period. Almost all patients were women with a
      mean age of 47 years old. The majority of patients were between 36 and 55 years
      old (69.1%) with a peak between 46 and 50 years. About 70% of the patients had
      already had advanced diseases (III and IV). Invasive ductal carcinoma was the
      commonest histopathological type (80%). The expression of ER, PR, c-erbB-2, and
      cathepsin D were evaluated in 55 patients. Metastases were found to occur in bone
      (24.4%), lungs (20.8%), and liver (10.7%). Among patients with bone metastasis,
      36 patients ((75%) were more than 40 years old and 32 (66.7%) had invasive ductal
      carcinomas. There was a significant correlation (p=0.011) between bone metastasis
      and histopathological type. No significant correlation was found between the use
      of hormonal contraceptives, ER/PR expression, c-erbB-2 and cathepsin D and bone
      metastasis. CONCLUSION: most breast cancer patients came in an already advanced
      stage, either locally or distant metastasis. The most common site of metastasis
      was the bone, followed by lungs and liver. Histopathological type of invasive
      ductal carcinoma was associated to the higher incidence of bone metastasis.
      Further studies are needed to identify patients with high risk of bone
      metastasis. There is also a need to evaluate predictive factors for the
      occurrence of bone metastasis at earlier stage.

PMID- 19153426
TI  - Is stenting a preferred option for unprotected left main coronary artery disease
      in the drug-eluting stent era?
AB  - Coronary artery bypass graft (CABG) has been the established treatment for left
      main coronary artery (LMCA) disease. However, despite continuous evolution of
      CABG including arterial grafting, advancement of cardioplegia, introduction of
      off-pump CABG, and improved pre-operative risk assessment, CABG has inherent
      limitations related to operation, such as peri-operative mortality, prolonged
      hospital stay and rehabilitation, and long-term graft patency. LMCA disease has
      been considered to be a challenge for interventional cardiologist for more than
      25 years. In the bare metal stent (BMS) era, early results were very promising,
      but the long-term results were not sufficient to replace CABG, mainly because of
      the high restenosis rate. The early experience with drug-eluting stent (DES) in
      unprotected LMCA reveals reduced rates of restenosis and associated clinical
      outcomes when compared with patients who were treated with BMS. Moreover, recent
      non-randomized study demonstrated that no differences in either mortality or the
      combined occurrence of major adverse cardiovascular and cerebrovascular events
      were observed at the 1-year follow-up between DES and CABG. However, up to now,
      effectiveness of DES is not enough to replace CABG in LMCA revascularization. The
      ongoing randomized trial comparing DES vs. CABG (PRE-COMBAT and SYNTAX) may help
      to address this issue. Based on these trials, it is likely that, for selected
      patients, DES may be regarded as a preferred revascularization strategy for LMCA
      disease.

PMID- 19153427
TI  - Late stent thrombosis with drug-eluting stents: the price to pay to prevent
      restenosis?
AB  - Drug-eluting stents have revolutionized the management of patients with coronary
      artery disease by decreasing the incidence of restenosis and the need for repeat
      revascularization. Recent data indicate that they may, however, be associated
      with a small but significant increase in the risk of late stent thrombosis
      compared with bare-metal stents. In this review, we discuss the incidence,
      pathogenesis, and predictors of stent thrombosis, the most important being
      premature cessation of dual antiplatelet therapy. Drug-eluting stent implantation
      needs to be carefully considered in every patient, and the risk of stent
      thrombosis and bleeding needs to be weighed against the risk of restenosis.
      Current guidelines recommend that dual antiplatelet therapy should be continued
      for at least 1 year following drug-eluting stent implantation, although the
      optimal duration of therapy is yet unknown.

PMID- 19153428
TI  - Percutaneous aortic valves: emerging.

PMID- 19153429
TI  - Stem-cell therapy for ischaemic cardiomyopathy.

PMID- 19153430
TI  - Percutaneous coronary intervention in China: registries and trials.

PMID- 19153432
TI  - Interventional practice in Australia and New Zealand: current trends.

PMID- 19153433
TI  - Computed tomography scan for cardiac interventions.

PMID- 19153434
TI  - Intravascular ultrasonography: using imaging endpoints in coronary
      atherosclerosis trials.

PMID- 19153435
TI  - Interventional cardiology: the past, present, and the future.

PMID- 19153436
TI  - Pathology of drug-eluting stents: implications for coronary intervention.
AB  - BACKGROUND: Polymer-based sirolimus (Cypher) and paclitaxel (Taxus) drug-eluting
      stents (DES) have become the treatment of choice for patients with symptomatic
      coronary artery disease. While these stents have reduced rates of restenosis and
      target lesion revascularization compared with bare metal stents (BMS), late
      thrombosis [i.e. stent thrombosis occurring > 30 days after percutaneous coronary
      intervention (PCI)], an often life-threatening complication, has emerged as a
      major safety concern. METHODS AND RESULTS: Using human pathological data, we have
      demonstrated that the current generation US Food and Drug Administration (FDA)
      Cypher and Taxus DES cause substantial impairment of arterial healing, defined as
      impaired re-endothelialization, persistent fibrin deposition, and absence or
      focal presence of smooth muscle cells covering the stent struts compared with
      BMS. This delay in healing constitutes the most important pathological substrate
      underlying cases of late DES thrombosis. CONCLUSIONS: This review will focus on
      the effects of these vascular implants in both animals and humans, especially as
      they relate to the process of late-stent thrombosis. We will use these data to
      make practical recommendations regarding anatomic and lesion considerations that
      may help the interventionalist to minimize the late thrombotic risk of these
      devices.

PMID- 19153437
TI  - Taxus vs. Cypher: making sense of the 'evidence-based' data.

PMID- 19153438
TI  - Newer stents: looking at the horizon.
AB  - More challenging and complex lesions are being treated with drug:eluting stents.
      This review examines advances in some of the commercially available stents
      together with important new stents under development. These include stents with
      novel platforms for drug elution, biodegradable, and bioabsorbable polymer/stents
      and stents dedicated to specific lesions. It also discusses novel pharmacological
      agents aimed at targeting inflammation and restenosis together with bio
      engineered stents and combination drug therapies.

PMID- 19153439
TI  - Diabetic multivessel disease: stenting vs. coronary artery bypass grafting.

PMID- 19153440
TI  - Revascularizing diabetics: the CARDia trial.

PMID- 19153441
TI  - Percutaneous coronary intervention for acute myocardial infarction: current
      strategy in the lab.

PMID- 19153442
TI  - Diverse DES usage: Indian perspective and data.

PMID- 19153443
TI  - Bifurcation stenting with drug-eluting stents.

PMID- 19153444
TI  - Crystals on the cover for 2009.

PMID- 19153445
TI  - The structure of Rph, an exoribonuclease from Bacillus anthracis, at 1.7 A
      resolution.
AB  - Maturation of tRNA precursors into functional tRNA molecules requires trimming of
      the primary transcript at both the 5' and 3' ends. Cleavage of nucleotides from
      the 3' stem of tRNA precursors, releasing nucleotide diphosphates, is
      accomplished in Bacillus by a phosphate-dependent exoribonuclease, Rph. The
      crystal structure of this enzyme from B. anthracis has been solved by molecular
      replacement to a resolution of 1.7 A and refined to an R factor of 19.3%. There
      is one molecule in the asymmetric unit; the crystal packing reveals the assembly
      of the protein into a hexamer arranged as a trimer of dimers. The structure shows
      two sulfate ions bound in the active-site pocket, probably mimicking the
      phosphate substrate and the phosphate of the 3'-terminal nucleotide of the tRNA
      precursor. Three other bound sulfate ions point to likely RNA-binding sites.

PMID- 19153446
TI  - The structure of d(CACACG).d(CGTGTG).
AB  - The crystal structure of d(CACACG).d(CGTGTG) was solved to a resolution of 2.05 A
      in space group P2(1). The duplex assumes the left-handed Z-DNA structure. The
      presence of two A.T base pairs in the hexamer does not greatly affect the
      conformation. The most significant changes compared with the regular structure of
      Z-DNA are in the values of twist in the central portion of the helix. This
      variation, as well as others in the values of roll, inclination etc., follow the
      pattern observed previously in the structure of d(CGCACG).d(CGTGCG).

PMID- 19153447
TI  - Crystallization and preliminary X-ray diffraction analysis of the complex between
      a human anti-interferon antibody fragment and human interferon alpha-2A.
AB  - Recombinant human interferon alpha-2A (rhIFN-alpha-2A) has been crystallized in
      complex with the recombinantly produced Fab fragment of a therapeutic monoclonal
      antibody (MEDI545; IgG1/kappa) which targets several human interferon alpha
      subtypes. This constitutes the first reported crystals of a human type I
      interferon bound to an antibody. The orthorhombic crystals belonged to either
      space group I222 or I2(1)2(1)2(1), with unit-cell parameters a = 134.82, b =
      153.26, c = 163.49 A. The diffraction of the crystals extended to 3.0 A
      resolution. The asymmetric unit contained two Fab-rhIFN-alpha-2A complexes. This
      corresponded to a crystal volume per protein weight (V(M)) of 3.02 A(3) Da(-1)
      and a solvent content of 59.3%. The corresponding three-dimensional structure is
      expected to shed light on the mechanism of action of MEDI545 and the molecular
      basis of its specificity.

PMID- 19153448
TI  - Crystallization and preliminary X-ray analysis of a C-terminal fragment of FlgJ,
      a putative flagellar rod cap protein from Salmonella.
AB  - The formation of the bacterial flagellar axial structure, including the filament,
      the hook and the rod, requires the attachment of a cap complex to the distal end
      of the growing structure. Because the rod penetrates the peptidoglycan (PG)
      layer, the rod cap complex is thought to have PG-hydrolyzing activity. FlgJ is a
      putative rod cap protein whose C-terminal region shows sequence similarity to
      known muramidases. In this study, FlgJ(120-316), a C-terminal fragment of FlgJ
      which contains the muramidase region, was overproduced, purified and
      crystallized. Crystals were obtained by the sitting-drop vapour-diffusion
      technique using PEG 3350 as a crystallizing agent and belonged to the
      orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 38.8, b =
      43.9, c = 108.5 A. Anomalous difference Patterson maps calculated from the
      diffraction data set of a selenomethionine-labelled crystal showed significant
      peaks in the Harker sections, indicating that the data were suitable for
      structure determination.

PMID- 19153449
TI  - Crystallization and preliminary X-ray diffraction analysis of GCIP/HHM
      transcriptional regulator.
AB  - GCIP/HHM is a human nuclear protein that is implicated in regulation of cell
      proliferation. Its primary structure contains helix-loop-helix and leucine-zipper
      motifs but lacks a DNA-binding basic region. Native and selenomethionine
      derivatized (SeMet) crystals of full-length GCIP/HHM were obtained using the
      hanging-drop vapour-diffusion method. The crystals were greatly improved by
      adding tris(2-carboxyethyl)phosphine as a reducing reagent and diffracted to 3.5
      A resolution. Preliminary phase calculations using the data set obtained from the
      SeMet crystal suggested that the crystal belonged to space group P3(2)21 and
      contained one molecule per asymmetric unit. Structure determination by the
      multiple-wavelength anomalous dispersion method using the SeMet crystals is in
      progress.

PMID- 19153451
TI  - Overexpression, purification, characterization and preliminary crystallographic
      study of phosphoglycolate phosphatase from Shigella flexneri 2a strain 301.
AB  - Phosphoglycolate phosphatase has a salvage function in the metabolism of the 2
      phosphoglycolate formed during bacterial DNA repair. In order to better
      understand its dimerization behaviour, the influence of metal ions on its
      activity and its catalytic mechanism at the molecular level, recombinant
      phosphoglycolate phosphatase from Shigella flexneri was overexpressed, purified,
      characterized and crystallized by the hanging-drop vapour-diffusion method at 291
      K using polyethylene glycol 3500 as a precipitant and zinc acetate as an
      additive. The crystals belonged to space group R3, with unit-cell parameters a =
      88.1, b = 88.1, c = 259.2 A, corresponding to the presence of two molecules in
      the asymmetric unit. SeMet-labelled protein was also prepared and crystallized
      for use in phase determination. Initial structure determination using the
      multiwavelength anomalous dispersion (MAD) method clearly revealed that SfPGPase
      bears an alpha-helical cap domain that differs from that of a previously reported
      orthologue.

PMID- 19153450
TI  - Crystallization and diffraction patterns of the oxy and cyano forms of the Lucina
      pectinata haemoglobins complex.
AB  - The native oxygen-carrier haemoglobins complex (HbII-III) is composed of
      haemoglobin II (HbII) and haemoglobin III (HbIII), which are found in the
      ctenidia tissue of the bivalve mollusc Lucina pectinata. This protein complex was
      isolated and purified from its natural source and crystallized using the vapour
      diffusion and capillary counter-diffusion methods. Oxy and cyano derivatives of
      the complex crystallized using several conditions, but the best crystals in terms
      of quality and size were obtained from sodium formate pH 5 using the counter
      diffusion method in a single capillary. Crystals of the oxy and cyano complexes,
      which showed a ruby-red colour and nonsingular prismatic shapes, scattered X-rays
      to resolution limits of 2.15 and 2.20 A, respectively, using a 0.886 A
      synchrotron-radiation source. The crystals belonged to the tetragonal system,
      space group P4(2)2(1)2, with unit-cell parameters a = b = 74.07, c = 152.07 and a
      = b = 73.83, c = 152.49 A for the oxy and cyano complexes, respectively. The
      asymmetric unit of both crystals is composed of a single copy of the heterodimer,
      with Matthew coefficients (V(M)) of 3.08 and 3.06 A(3) Da(-1) for the oxy and
      cyano complexes, respectively, which correspond to a solvent content of
      approximately 60.0% by volume.

PMID- 19153452
TI  - Crystallization and preliminary crystallographic analysis of cgHle, a homoserine
      acetyltransferase homologue, from Corynebacterium glutamicum.
AB  - CgHle is an enzyme that is encoded by gene cg0961 from Corynebacterium
      glutamicum. The physiological function of cgHle is so far unclear. Bioinformatic
      annotations based on sequence homology indicated that cgHle may be an acetyl
      CoA:homoserine acetyl transferase and as such may be involved in methionine
      biosynthesis, but recent evidence has shown that it is an esterase that catalyzes
      the hydrolysis of acetyl esters. Here, the crystallization of cgHle in two
      orthorhombic crystal forms, a trigonal crystal form and a monoclinic crystal form
      is described. The trigonal crystals have a solvent content of 83.7%, which is one
      of the highest solvent contents ever found for protein crystals. One of the
      orthorhombic crystals diffracted X-rays to at least 1.2 A resolution.

PMID- 19153453
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of
      glutathionylated Trx1 C33S mutant from yeast.
AB  - Thioredoxins (Trxs) are a family of small redox-active proteins that are found in
      all living organisms. In Saccharomyces cerevisiae, two cytosolic Trxs (Trx1 and
      Trx2) and one mitochondrial Trx (Trx3) have previously been identified. In this
      work, cytosolic Trx1 containing a C33S mutant was overexpressed, purified,
      glutathionylated and crystallized using the hanging-drop vapour-diffusion method.
      A set of X-ray diffraction data was collected to 1.80 A resolution. The crystal
      belonged to space group P1, with unit-cell parameters a = 38.53, b = 38.81, c =
      41.70 A, alpha = 72.91, beta = 87.51, gamma = 60.58 degrees.

PMID- 19153454
TI  - Purification and crystallization of Cor a 9, a major hazelnut allergen.
AB  - Hazelnut (Corylus avellana) is one of the food sources that induce allergic
      reaction in a subpopulation of people with food allergy. The 11S legumin-like
      seed-storage protein from hazelnut has been identified as one of the major
      hazelnut allergens and named Cor a 9. In this study, Cor a 9 was extracted from
      hazelnut kernels using a high-salt solution and was purified by desalting out and
      FPLC to a highly purified state. Diffraction-quality single crystals were
      obtained using the hanging-drop vapour-diffusion method. Diffraction data were
      collected and a structure solution has been obtained by molecular-replacement
      calculations. Further refinement of the structure is currently in progress.

PMID- 19153456
TI  - Cloning, expression, crystallization and preliminary X-ray crystallographic
      analysis of glutamyl-tRNA synthetase (Xoo1504) from Xanthomonas oryzae pv.
      oryzae.
AB  - The gltX gene from Xanthomonas oryzae pv. oryzae (Xoo1504) encodes glutamyl-tRNA
      synthetase (GluRS), one of the most important enzymes involved in bacterial
      blight (BB), which causes huge production losses of rice worldwide. GluRS is a
      class I-type aminoacyl-tRNA synthetase (aaRS) that is primarily responsible for
      the glutamylation of tRNA(Glu). It plays an essential role in protein synthesis,
      as well as the regulation of cells, in all organisms. As it represents an
      important target for the development of new antibacterial drugs against BB,
      determination of the three-dimensional structure of GluRS is essential in order
      to understand its catalytic mechanism. In order to analyze its structure and
      function, the gltX gene was cloned and the GluRS enzyme was expressed, purified
      and then crystallized. A GluRS crystal belonging to the monoclinic space group C2
      diffracted to 2.8 A resolution and had unit-cell parameters a = 186.8, b = 108.4,
      c = 166.1 A, beta = 96.3 degrees . The unit-cell volume of the crystal allowed
      the presence of six to eight monomers in the asymmetric unit, with a
      corresponding Matthews coefficient (V(M)) range of 2.70-2.02 A(3) Da(-1) and a
      solvent-content range of 54.5-39.3%.

PMID- 19153455
TI  - Crystallization and preliminary X-ray analysis of FliJ, a cytoplasmic component
      of the flagellar type III protein-export apparatus from Salmonella sp.
AB  - The axial component proteins of the bacterial flagellum are synthesized in the
      cytoplasm and then translocated into the central channel of the flagellum by the
      flagellar type III protein-export apparatus for self-assembly at the distal
      growing end of the flagellum. FliJ is an essential cytoplasmic component of the
      export apparatus. In this study, Salmonella FliJ with an extra three residues
      (glycine, serine and histidine) attached to the N-terminus as the remainder of a
      His tag (GSH-FliJ) was purified and crystallized. Crystals were obtained by the
      sitting-drop vapour-diffusion technique using PEG 300 as a precipitant. GSH-FliJ
      crystals grew in the hexagonal space group P6(1)22 or P6(5)22. While the native
      crystals diffracted to 3.3 A resolution, the diffraction resolution limit of
      mercury derivatives was extended to 2.1 A. Anomalous and isomorphous difference
      Patterson maps of the mercury-derivative crystal showed significant peaks in
      their Harker sections, indicating the usefulness of the derivative data for
      structure determination.

PMID- 19153457
TI  - Cloning, expression, purification, crystallization and preliminary X-ray analysis
      of the pilus-associated sortase C from Streptococcus pneumoniae.
AB  - The pilus-associated sortase C from Streptococcus pneumoniae (SrtC or Srt-2) acts
      as a polymerase for the pilus subunit proteins RrgA and RrgB. Here, the
      crystallization and preliminary X-ray diffraction analysis of three crystal forms
      of SrtC are reported. One crystal form belongs to space group P2(1)2(1)2(1), with
      unit-cell parameters a = 48.9, b = 96.9, c = 98.9 A, alpha = beta = gamma = 90
      degrees . The other two crystal forms belong to space group P222, with unit-cell
      parameters a = 48.8, b = 97.2, c = 99.2 A, alpha = beta = gamma = 90 degrees and
      a = 48.6, b = 96.5, c = 98.8 A, alpha = beta = gamma = 90 degrees , respectively.
      Preliminary analysis indicates the presence of two molecules in the asymmetric
      unit of the crystal for all three forms.

PMID- 19153458
TI  - X-ray diffraction analysis of a human tRNA(Gly) acceptor-stem microhelix
      isoacceptor at 1.18 A resolution.
AB  - Interest has been focused on comparative X-ray structure analyses of different
      tRNA(Gly) acceptor-stem helices. tRNA(Gly)/glycyl-tRNA synthetase belongs to the
      so-called class II system, in which the tRNA identity elements consist of simple
      and unique determinants that are located in the tRNA acceptor stem and the
      discriminator base. Comparative structure investigations of tRNA(Gly)
      microhelices provide insight into the role of tRNA identity elements. Predominant
      differences in the structures of glycyl-tRNA synthetases and in the tRNA identity
      elements between prokaryotes and eukaryotes point to divergence during the
      evolutionary process. Here, the crystallization and high-resolution X-ray
      diffraction analysis of a human tRNA(Gly) acceptor-stem microhelix with sequence
      5'-G(1)C(2)A(3)U(4)U(5)G(6)G(7)-3', 5'-C(66)C(67)A(68)A(69)U(70)G(71)C(72)-3' is
      reported. The crystals belonged to the monoclinic space group C2, with unit-cell
      parameters a = 37.32, b = 37.61, c = 30.47 A, beta = 112.60 degrees and one
      molecule per asymmetric unit. A data set was collected using synchrotron
      radiation and data were processed within the resolution range 50.0-1.18 A. The
      structure was solved by molecular replacement.

PMID- 19153460
TI  - Features of homotetrameric molecular association in protein crystals.
AB  - The crystal structures of proteins showing homotetrameric association, a common
      feature observed in many lectins, have been analyzed in order to understand the
      characteristics of tetrameric association in terms of the arrangement of subunits
      and their biological significance. The analysis could group the tetramer units
      into the following four categories. (i) Tetrahedral molecules, in which the four
      monomers form a nearly perfect tetrahedral arrangement. The angle between the
      axes of any two monomers is approximately 109 degrees. (ii) Molecules that form a
      sandwiched dimer of dimers in which the two dimers are arranged perpendicular to
      each other, one upon the other. (iii) Planar molecules, in which the four
      monomers lie in one plane and the corresponding sides of adjacent monomers face
      in opposite directions. This can be considered as a flattened tetrahedral shape.
      (iv) Planar closed molecules, in which all four monomers lie in one plane
      arranged in a head-to-tail fashion in a square. The first group and its variant,
      the third group, are the most commonly found arrangements in crystal structures.
      Each arrangement has its own importance for biological function. Some tetrameric
      assemblies that deviate from the majority described above also have relevance to
      their biological function.

PMID- 19153461
TI  - Structure of NS1A effector domain from the influenza A/Udorn/72 virus.
AB  - The nonstructural protein NS1A from influenza virus is a multifunctional
      virulence factor and a potent inhibitor of host immunity. It has two functional
      domains: an N-terminal 73-amino-acid RNA-binding domain and a C-terminal effector
      domain. Here, the crystallographic structure of the NS1A effector domain of
      influenza A/Udorn/72 virus is presented. Structure comparison with the NS1
      effector domain from mouse-adapted influenza A/Puerto Rico/8/34 (PR8) virus
      strain reveals a similar monomer conformation but a different dimer interface.
      Further analysis and evaluation shows that the dimer interface observed in the
      structure of the PR8 NS1 effector domain is likely to be a crystallographic
      packing effect. A hypothetical model of the intact NS1 dimer is presented.

PMID- 19153462
TI  - The Biomolecular Crystallization Database Version 4: expanded content and new
      features.
AB  - The Biological Macromolecular Crystallization Database (BMCD) has been a publicly
      available resource since 1988, providing a curated archive of information on
      crystal growth for proteins and other biological macromolecules. The BMCD content
      has recently been expanded to include 14 372 crystal entries. The resource
      continues to be freely available at http://xpdb.nist.gov:8060/BMCD4. In addition,
      the software has been adapted to support the Java-based Lucene query language,
      enabling detailed searching over specific parameters, and explicit search of
      parameter ranges is offered for five numeric variables. Extensive tools have been
      developed for import and handling of data from the RCSB Protein Data Bank. The
      updated BMCD is called version 4.02 or BMCD4. BMCD4 entries have been expanded to
      include macromolecule sequence, enabling more elaborate analysis of relations
      among protein properties, crystal-growth conditions and the geometric and
      diffraction properties of the crystals. The BMCD version 4.02 contains greatly
      expanded content and enhanced search capabilities to facilitate scientific
      analysis and design of crystal-growth strategies.

PMID- 19153464
TI  - Distal histidine conformational flexibility in dehaloperoxidase from Amphitrite
      ornata.
AB  - The enzyme dehaloperoxidase (DHP) from the terebellid polychaete Amphitrite
      ornata is a heme protein which has a globin fold but can function as both a
      hemoglobin and a peroxidase. As a peroxidase, DHP is capable of converting 2,4,6
      trihalophenols to the corresponding 2,6-dihaloquinones in the presence of
      hydrogen peroxide. As a hemoglobin, DHP cycles between the oxy and deoxy states
      as it reversibly binds oxygen for storage. Here, it is reported that the distal
      histidine, His55, exhibits conformational flexibility in the deoxy form and is
      consequently observed in two solvent-exposed conformations more than 9.5 A away
      from the heme. These conformations are analogous to the open conformation of
      sperm whale myoglobin. The heme iron in deoxy ferrous DHP is five-coordinate and
      has an out-of-plane displacement of 0.25 A from the heme plane. The observation
      of five-coordinate heme iron with His55 in a remote solvent-exposed conformation
      is consistent with the hypothesis that His55 interacts with heme iron ligands
      through hydrogen bonding in the closed conformation. Since His55 is also
      displaced by the binding of 4-iodophenol in an internal pocket, these results
      provide new insight into the correlation between heme iron ligation, molecular
      binding in the distal pocket and the conformation of the distal histidine in DHP.

PMID- 19153463
TI  - Structures of the multicomponent Rieske non-heme iron toluene 2,3-dioxygenase
      enzyme system.
AB  - Bacterial Rieske non-heme iron oxygenases catalyze the initial hydroxylation of
      aromatic hydrocarbon substrates. The structures of all three components of one
      such system, the toluene 2,3-dioxygenase system, have now been determined. This
      system consists of a reductase, a ferredoxin and a terminal dioxygenase. The
      dioxygenase, which was cocrystallized with toluene, is a heterohexamer containing
      a catalytic and a structural subunit. The catalytic subunit contains a Rieske
      [2Fe-2S] cluster and mononuclear iron at the active site. This iron is not
      strongly bound and is easily removed during enzyme purification. The structures
      of the enzyme with and without mononuclear iron demonstrate that part of the
      structure is flexible in the absence of iron. The orientation of the toluene
      substrate in the active site is consistent with the regiospecificity of oxygen
      incorporation seen in the product formed. The ferredoxin is Rieske type and
      contains a [2Fe-2S] cluster close to the protein surface. The reductase belongs
      to the glutathione reductase family of flavoenzymes and consists of three
      domains: an FAD-binding domain, an NADH-binding domain and a C-terminal domain. A
      model for electron transfer from NADH via FAD in the reductase and the ferredoxin
      to the terminal active-site mononuclear iron of the dioxygenase is proposed.

PMID- 19153465
TI  - Structure of relaxed-state human hemoglobin: insight into ligand uptake,
      transport and release.
AB  - Hemoglobin was one of the first protein structures to be determined by X-ray
      crystallography and served as a basis for the two-state MWC model for the
      mechanism of allosteric proteins. Since then, there has been an ongoing debate
      about whether Hb allostery involves the unliganded tense T state and the liganded
      relaxed R state or whether it involves the T state and an ensemble of liganded
      relaxed states. In fact, the former model is inconsistent with many functional
      observations, as well as the recent discoveries of several relaxed-state Hb
      structures such as RR2, R3 and R2. One school of thought has suggested the R2
      state to be the physiologically relevant relaxed end state, with the R state
      mediating the T-->R2 transition. X-ray studies have been performed on human
      carbonmonoxy Hb at a resolution of 2.8 A. The ensuing liganded quaternary
      structure is different from previously reported liganded Hb structures. The
      distal beta-heme pocket is the largest when compared with other liganded Hb
      structures, partly owing to rotation of betaHis63(E7) out of the distal pocket,
      creating a ligand channel to the solvent. The structure also shows unusually
      smaller alpha- and beta-clefts. Results from this study taken in conjunction with
      previous findings suggest that multiple liganded Hb states with different
      quaternary structures may be involved in ligand uptake, stabilization, transport
      and release.

PMID- 19153466
TI  - Sugar-complex structures of the C-half domain of the galactose-binding lectin
      EW29 from the earthworm Lumbricus terrestris.
AB  - R-type lectins are one of the most prominent types of lectin; they exist
      ubiquitously in nature and mainly bind to the galactose unit of sugar chains. The
      galactose-binding lectin EW29 from the earthworm Lumbricus terrestris belongs to
      the R-type lectin family as represented by the plant lectin ricin. It shows
      haemagglutination activity and is composed of a single peptide chain that
      includes two homologous domains: N-terminal and C-terminal domains. A truncated
      mutant of EW29 comprising the C-terminal domain (rC-half) has haemagglutination
      activity by itself. In order to clarify how rC-half recognizes ligands and shows
      haemagglutination activity, X-ray crystal structures of rC-half in complex with D
      lactose and N-acetyl-D-galactosamine have been determined. The structure of rC
      half is similar to that of the ricin B chain and consists of a beta-trefoil fold;
      the fold is further divided into three similar subdomains referred to as
      subdomains alpha, beta and gamma, which are gathered around the pseudo-threefold
      axis. The structures of sugar complexes demonstrated that subdomains alpha and
      gamma of rC-half bind terminal galactosyl and N-acetylgalactosaminyl glycans. The
      sugar-binding properties are common to both ligands in both subdomains and are
      quite similar to those of ricin B chain-lactose complexes. These results indicate
      that the C-terminal domain of EW29 uses these two galactose-binding sites for its
      function as a single-domain-type haemagglutinin.

PMID- 19153467
TI  - The structure of the BIR3 domain of cIAP1 in complex with the N-terminal peptides
      of SMAC and caspase-9.
AB  - The inhibitor of apoptosis protein (IAP) family of molecules inhibit apoptosis
      through the suppression of caspase activity. It is known that the XIAP protein
      regulates both caspase-3 and caspase-9 through direct protein-protein
      interactions. Specifically, the BIR3 domain of XIAP binds to caspase-9 via a
      ;hotspot' interaction in which the N-terminal residues of caspase-9 bind in a
      shallow groove on the surface of XIAP. This interaction is regulated via SMAC,
      the N-terminus of which binds in the same groove, thus displacing caspase-9. The
      mechanism of suppression of apoptosis by cIAP1 is less clear. The structure of
      the BIR3 domain of cIAP1 (cIAP1-BIR3) in complex with N-terminal peptides from
      both SMAC and caspase-9 has been determined. The binding constants of these
      peptides to cIAP1-BIR3 have also been determined using the surface plasmon
      resonance technique. The structures show that the peptides interact with cIAP1 in
      the same way that they interact with XIAP: both peptides bind in a similar
      shallow groove in the BIR3 surface, anchored at the N-terminus by a charge
      stabilized hydrogen bond. The binding data show that the SMAC and caspase-9
      peptides bind with comparable affinities (85 and 48 nM, respectively).

PMID- 19153468
TI  - Structure of a highly stable mutant of human fibroblast growth factor 1.
AB  - Fibroblast growth factors (FGFs) are involved in diverse cellular processes such
      as cell migration, angiogenesis, osteogenesis, wound healing and embryonic and
      foetal development. Human acidic fibroblast growth factor (FGF-1) is the only
      member of the FGF family that binds with high affinity to all four FGF receptors
      and thus is considered to be the human mitogen with the broadest specificity.
      However, pharmacological applications of FGF-1 are limited owing to its low
      stability. It has previously been reported that the introduction of single
      mutations can significantly improve the stability of FGF-1 and its resistance to
      proteolytic degradation. Here, the structure of the Q40P/S47I/H93G triple mutant
      of FGF-1, which exhibits much higher stability, a prolonged half-life and
      enhanced mitogenic activity, is presented. Compared with the wild-type structure,
      three localized conformational changes in the stable triple mutant were observed,
      which is in agreement with the perfect energetic additivity of the single
      mutations described in a previous study. The huge change in FGF-1 stability (the
      denaturation temperature increased by 21.5 K, equivalent to DeltaDeltaG(den) =
      24.3 kJ mol(-1)) seems to result from the formation of a short 3(10)-helix
      (position 40), an improvement in the propensity of amino acids to form beta
      sheets (position 47) and the rearrangement of a local hydrogen-bond network
      (positions 47 and 93).

PMID- 19153469
TI  - Structural and functional role of water molecules in bovine pancreatic
      phospholipase A(2): a data-mining approach.
AB  - The water molecules in 25 (21 high-resolution and four atomic resolution) crystal
      structures of bovine pancreatic phospholipase A(2) have been analyzed in order to
      identify the invariant water molecules and their possible roles. A total of 24
      water molecules have been identified that are invariant in all 25 crystal
      structures examined. These include the catalytic water molecule, which is
      directly involved in the enzyme mechanism, and the conserved structural water
      molecule, which stabilizes the extended hydrogen-bonding network of the active
      site. Furthermore, many other water molecules stabilize the structure, whilst a
      few have been found to maintain the active-site geometry and provide coordination
      to the functionally important calcium ion. The invariant water molecules have
      been carefully examined and their possible roles in the structure and/or function
      are discussed. Molecular-dynamics studies of all 25 crystal structures have also
      been carried out and the results provide a good explanation of and support the
      findings obtained from the crystal structures.

PMID- 19153471
TI  - Hans C. Freeman (1929-2008).

PMID- 19153470
TI  - Atomic resolution structure of pseudoazurin from the methylotrophic denitrifying
      bacterium Hyphomicrobium denitrificans: structural insights into its
      spectroscopic properties.
AB  - The crystal structure of native pseudoazurin (HdPAz) from the methylotrophic
      denitrifying bacterium Hyphomicrobium denitrificans has been determined at a
      resolution of 1.18 A. After refinement with SHELX employing anisotropic
      displacement parameters and riding H atoms, R(work) and R(free) were 0.135 and
      0.169, respectively. Visualization of the anisotropic displacement parameters as
      thermal ellipsoids provided insight into the atomic motion within the perturbed
      type 1 Cu site. The asymmetric unit includes three HdPAz molecules which are
      tightly packed by head-to-head cupredoxin dimer formation. The shape of the Cu
      atom ellipsoid implies significant vibrational motion diagonal to the equatorial
      xy plane defined by the three ligands (two His and one Cys). The geometric
      parameters of the type 1 Cu site in the HdPAz structure differ unambiguously from
      those of other pseudoazurins. It is demonstrated that their structural aspects
      are consistent with the unique visible absorption spectrum.

PMID- 19153473
TI  - Codon and aminoacid usage patterns in mycobacteria.
AB  - The large number of organisms and of genes sequenced at the present time permits
      now to study molecular evolution in such lower clades as genera, species, and
      subspecies. Here, we focus our attention on the genus Mycobacterium, in which we
      examined codon and aminoacid usage in 13 species, and in 12 subspecies for a
      total of 8,836,513 codons from 26,755 sequences. Within the genus Mycobacterium,
      frequencies of codon and aminoacid usage correlate between species and between
      subspecies. In the groups studied, aminoacid molecular weight and codon
      degeneracy influence correlations between frequencies, while GC content is the
      main factor influencing the effective number of codons. The coding GC, which is
      highly correlated with total genomic GC content, seems to be the main factor
      influencing present synonymous codon usage in the genus. In particular, the GC
      content at the 3rd base position seems to shape heavily the effective number of
      codons, giving indication that here mutational bias dominates over translational
      selection. Evolutionary trees based on codon and aminoacid usage are consistent
      with traditional phylogenies of species within the genus.

PMID- 19153474
TI  - Aggressive natural killer cell leukemia: is Epstein-Barr virus negativity an
      indicator of a favorable prognosis?
AB  - Aggressive natural killer (NK) cell leukemia (ANKL) is a prototype of an Epstein
      Barr virus (EBV)-associated lymphoid malignancy, which is characterized by a
      fulminant clinical course and a median survival interval <2 months. EBV
      negativity in ANKL is uncommon, and the characteristics of EBV-negative ANKL are
      not well defined. We compared the clinicopathological characteristics of EBV
      negative ANKL patients (group 1, n = 2) with those of EBV-positive ANKL patients
      (group 2, n = 14) and reviewed the literature for reports on EBV-negative ANKL
      cases. EBV-negative and EBV-positive ANKL patients had similar clinical and
      pathological characteristics, but EBV-negative patients had a longer survival
      than EBV-positive patients (11.5 vs. 1.5 months, respectively). EBV-negative
      patients achieved complete remission, but tumors often relapsed after a short
      interval. In conclusion, EBV-negative ANKL is an uncommon malignancy that pursues
      a less aggressive clinical course than EBV-positive ANKL.

PMID- 19153475
TI  - Methylation status of promoter-associated CpG islands in primary acute myeloid
      leukemia.

PMID- 19153476
TI  - Increased serum 90K and Galectin-3 expression are associated with advanced stage
      and a worse prognosis in diffuse large B-cell lymphomas.
AB  - The role of 90K and galectin-3 in cell-to-extracellular matrix adhesion and tumor
      metastasis has been reported, but little is known about their role in the
      prognosis and extranodal involvement of diffuse large B-cell lymphomas (DLBCL).
      Thus, we measured serum 90K concentration by enzyme-linked immunosorbent assay
      and tissue expression of galectin-3 by immunohistochemistry in newly diagnosed
      DLBCL patients. The mean serum 90K concentration was higher in DLBCL than in
      healthy controls (1,408.81 +/- 89.45 vs. 980.94 +/- 58.69 ng/ml, p = 0.036). High
      serum 90K (median value >or=1,249.50 ng/ml) and high galectin-3 expression (grade
      3 positive staining in >75% of cells) showed a significant association with stage
      III/IV, >or=2 extranodal involvements and risk of high/high-intermediate
      international prognostic index (p < 0.05). The complete response (CR) rate
      (86.9%, 20/23) in the low 90K group was higher than in the high 90K group (56.5%,
      13/23). Among 14 patients with high galectin-3 expression, only 6 patients showed
      CR (42.9%). The time to progression and overall survival were shorter in the
      group with high 90K and galectin-3 expression (p < 0.05). In conclusion, serum
      90K and galectin-3 expression might be useful markers to indicate the extent of
      lymphoma involvement and prognosis in DLBCL.

PMID- 19153478
TI  - Nitric oxide metabolites, leukocyte activation markers and oxidative status in
      dialyzed subjects.
AB  - AIMS: Our purpose was to evaluate, in a group of 42 end-stage renal disease
      patients who regularly undergo hemodialysis, some indexes of leukocyte
      activation, nitric oxide metabolites (NOx) and other parameters that reflect the
      oxidative stress before and after a standard hemodialysis session. METHODS:
      Elastase and myeloperoxidase (MPO) were determined by means of ELISA. The NO
      production was evaluated by a micromethod which measures the concentration of
      NOx. The oxidation of polyunsaturated fatty acids was evaluated in plasma by
      detection of thiobarbituric acid-reactive substances (TBARS). Total antioxidant
      status (TAS) was obtained using spectrophotometry. RESULTS: At baseline, we
      observed an increase of elastase, NOx, TBARS and TAS, without any variation of
      MPO. After the dialysis session, we found an increase in elastase and MPO, a
      decrease in NOx and TAS and no variation in TBARS. No modification occurred after
      subdividing the patients in two subgroups. CONCLUSIONS: Our data confirm the
      involvement of leukocytes and oxidative stress in hemodialysis patients.

PMID- 19153479
TI  - Man-in-the-barrel syndrome with combination of infarctions in the anterior spinal
      artery and posterior inferior cerebellar artery territories.

PMID- 19153477
TI  - Polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) are associated
      with albuminuria in hypertensive African Americans: the HyperGEN study.
AB  - BACKGROUND: MYH9 is a podocyte-expressed gene encoding nonmuscle myosin IIA that
      is associated with idiopathic and human immunodeficiency virus-associated focal
      segmental glomerulosclerosis (FSGS) and hypertensive end-stage renal disease in
      African Americans. METHODS: Four single nucleotide polymorphisms comprising the
      major MYH9 E1 risk haplotype were tested for association with estimated
      glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (ACR) in
      2,903 HyperGEN participants (1,458 African Americans (AA) in 895 families and
      1,445 European Americans (EA) in 859 families) to determine the role of MYH9 in
      subclinical nephropathy. Association analyses employed general linear models in
      unrelated probands and generalized estimating equations in families. Adjustment
      was performed for age, sex, diabetes, BMI, medications, and mean arterial
      pressure separately in each race. RESULTS: Mean (SD) eGFR and ACR were 74.3
      (16.0) ml/min/1.73 m(2) and 20.3 (119.9) mg/g in EA, and 88.6 (20.9) ml/min/1.73
      m(2) and 76.8 (394.5) mg/g in AA (both p < 0.0001 across ethnicities). Urine ACR
      was associated with rs3752462 (p = 0.01) and rs4821481 (p = 0.05) in unrelated AA
      and with rs4821481 (p = 0.03), rs2032487 (p = 0.04) and the E1 3224 haplotype (p
      = 0.013) in AA families. Single nucleotide polymorphisms and the haplotype were
      not associated with ACR in EA or with eGFR in either ethnic group. CONCLUSIONS:
      MYH9 variants are associated with albuminuria in hypertensive AA. The strength of
      the association was weaker than that in FSGS and hypertensive end-stage renal
      disease. MYH9 risk variants appear to be associated with primary FSGS with
      secondary hypertension, although nephrosclerosis may develop in response to
      hypertension in subjects homozygous for the MYH9 E1 risk haplotype.

PMID- 19153480
TI  - Bilateral vertebral-artery-dissecting aneurysm causing subarachnoid hemorrhage
      cured by staged endovascular reconstruction after occlusion.

PMID- 19153481
TI  - Reversibility of basilar artery stenosis following timely treatment of temporal
      arteritis.

PMID- 19153483
TI  - Epigenetic alterations in cholangiocarcinoma-sustained IL-6/STAT3 signaling in
      cholangio- carcinoma due to SOCS3 epigenetic silencing.
AB  - Cholangiocarcinoma (CCA) is a highly lethal malignant tumor arising from the
      biliary tract epithelium, characterized by its typically late clinical
      presentation and lack of effective therapeutic modalities. Chronic inflammatory
      conditions, including primary sclerosing cholangitis, liver fluke infestation and
      hepatolithiasis, are listed in the risk factors, but for most cases of CCA the
      cause is unknown. Recent advances in molecular pathogenesis have highlighted the
      importance of epigenetic alterations including promoter hypermethylation and
      histone deacetylation in addition to genetic changes in the process of
      cholangiocarcinogenesis. This review provides a comprehensive overview of the
      genes hypermethylated in CCA to date and their putative roles in
      cholangiocarcinogenesis. Among genes hypermethylated, we found the CpG island
      hypermethylation in suppressor of cytokine signaling 3 (SOCS3) gene promoter in
      CCA. Interleukin-6 (IL-6)-mediated signal transducers and activators of
      transcription 3 (STAT3) activation are aberrantly sustained in CCA cells,
      resulting in resistance to apoptosis. SOCS3 controls the IL-6/STAT3 signaling
      pathway by a classic feedback loop. Indeed, SOCS3 epigenetic silencing is
      responsible for sustained IL-6/STAT3 signaling in CCA. These findings provide new
      perspectives for epigenetic therapy to restore SOCS3 in this cancer.

PMID- 19153484
TI  - Proposal of a new hypothesis on the development of colorectal epithelial
      neoplasia: nonspecific inflammation--colorectal Paneth cell metaplasia-
      colorectal epithelial neoplasia.
AB  - Colorectal epithelial neoplasia (CR-EN), both adenoma and adenocarcinoma, may
      develop from the essential tubules of the colorectum. In order to conclude the
      carcinogenesis of the colorectal cancer more clearly, the biological features
      including the genetic abnormality of the nonneoplastic mucosal epithelium of
      colon and rectum, which coexist in connection with CR-EN, should be investigated.
      In this review, the importance of Paneth cell metaplasia of colorectum as one of
      the original mucosal regions of the development of CR-EN, and the new hypothesis
      on the development of CR-EN (nonspecific inflammation - colorectal Paneth cell
      metaplasia - colorectal epithelial neoplasia) are examined.

PMID- 19153485
TI  - Investigation of gastric emptying disorders in patients with functional dyspepsia
      reveals impaired inhibitory gastric emptying regulation in the early postcibal
      period.
AB  - BACKGROUND/AIMS: The aim of the study was to investigate gastric emptying
      profiles in patients with postprandial distress syndrome (PDS) as a means to
      understand relationships between gastric emptying and dyspepsia. METHODS: Gastric
      emptying times were measured using a (13)C breath test. In addition to
      comparisons of (13)C half excretion times (t 1/2 ex) between patients with PDS
      and healthy subjects, gastric emptying (%dose/h) curves were analyzed using a
      multipeak curve-fitting technique, and fitted curves were differentiated to
      measure the slope of curves for each time point. RESULTS: (1) During the early
      postcibal period, the slope of %dose/h curves in 27% of patients with PDS was
      larger than the average slope derived from healthy subjects. The t 1/2 ex was
      also higher in these patients relative to healthy subjects. (2) During the
      midpostcibal period, the slope of %dose/h curves in 36% of PDS patients was
      larger than the average slope derived from healthy subjects. There was a trend
      toward lower t 1/2 ex values for these patients relative to control subjects. (3)
      When t 1/2 ex was calculated overall, however, there was no significant
      difference between healthy subjects and patients with PDS. CONCLUSION: Our
      findings document abnormal gastric outflow in patients with PDS. In some
      patients, there appears to be a significant correspondence between PDS-related
      dyspepsia and accelerated gastric emptying in the early postcibal period, whereas
      other patients showed a similar correspondence between dyspepsia and impaired
      inhibitory gastric emptying regulation in the midpostcibal period.

PMID- 19153486
TI  - Stepwise diagnosis and treatment from uninvestigated dyspepsia to functional
      dyspepsia in clinical practice in Japan: proposal of a 4-step algorithm.
AB  - BACKGROUND/AIM: Management of dyspepsia may differ between countries. In Japan,
      Helicobacter pylori infection should be considered because of the high prevalence
      of the infection and the related diseases. I tried to propose an algorithm for
      stepwise diagnosis and treatment from uninvestigated dyspepsia to functional
      dyspepsia in clinical practice in Japan. METHODS: A proposal was made from my
      personal review of published studies. RESULTS: A 4-step algorithm was proposed.
      In the first step, organic, systemic or metabolic diseases are excluded and
      nonulcer dyspepsia (NUD) is diagnosed. The second step is to test and treat H.
      pylori infection for NUD patients. In the third step, proton pump inhibitor (PPI)
      responsive NUD is discriminated by PPI. Nonresponsive patients in the third step
      are diagnosed as having PPI-resistant NUD. In the fourth step, functional
      dyspepsia is diagnosed with the Rome III questionnaire. In this algorithm, it is
      not necessary to do special function tests for functional gastrointestinal
      disorders. Treatment options are automatically restricted in each step.
      CONCLUSIONS: The proposed 4-step algorithm may be useful in clinical practice for
      the diagnosis from uninvestigated dyspepsia to functional dyspepsia in Japan.
      With this stepwise algorithm, treatment options are restricted in each step and
      the management of dyspepsia may be easier.

PMID- 19153487
TI  - Adiposity and gastrointestinal malignancy.
AB  - Recent epidemiologic studies have shown a positive association between obesity
      and certain cancers. Our retrospective studies show that hypertriglyceridemia is
      an independent risk factor for the development of colonic adenoma and nodal
      metastasis in early gastric and esophageal cancer in men. High-fat condition may
      be favorable for the growth of malignant cells. Serum level of adiponectin is
      reduced in patients with advanced gastric cancer, which may be associated with
      the positive link between adiposity and cancer. In early gastric cancer, patients
      with undifferentiated type have lower fat volume than those with differentiated
      type. Adiposity appears to be closely related with various aspects in
      pathophysiology of gastrointestinal malignancy.

PMID- 19153488
TI  - The difference in p53 mutations between cancers of the upper and lower
      gastrointestinal tract.
AB  - BACKGROUND: p53 gene mutations have been reported in over half of all human
      cancers and they appear to occur in the early stage of cancer, thus indicating
      the important role that such mutations may play in the carcinogenesis of the
      digestive tract. This study investigated the differences in p53 abnormalities
      between cancers of the upper and lower gastrointestinal tract. MATERIALS AND
      METHODS: The DNA of 354 specimens of gastrointestinal cancer (esophagus 85,
      stomach 112, colon 157) was extracted and then p53 gene mutations were
      investigated by direct sequencing; the loss of heterozygosity was also
      synchronously analyzed in all cases. RESULTS: (1) p53 gene mutation: p53 gene
      mutations were found in 41 samples (48.2%) in the esophagus, 18 samples (16.0%)
      in the stomach and 36 samples (22.9%) in the colon. p53 mutations were more
      frequently identified in well-differentiated cancers and a close correlation was
      recognized between p53 mutations and loss of heterozygosity. (2) Mutation
      spectrum: the ratio of transversion was 43.9% in esophagus, 33.3% in stomach and
      25.0% in the colon tumors. Reciprocally, the ratio of transition was 31.7, 66.7,
      and 72.2%, respectively. DISCUSSION: The frequency of p53 transversion mutations
      was extremely high in the upper digestive tract, whereas transition mutations
      were more frequently observed in the lower digestive tract. The investigation of
      the spectrum of mutations in p53 is therefore expected to lead to a better
      understanding of the agents responsible for inducing cancer.

PMID- 19153489
TI  - Pathological diagnosis of early colorectal carcinoma and its clinical
      implications.
AB  - This review consists of 6 sections: (1) pathological diversity of cancer and the
      correlation between 'zokushutsu' (budding/sprouting) and lymph node metastasis;
      (2) genetic analysis and metastasis in the gastrointestinal tract; (3) conditions
      requiring resection after endoscopic treatment; (4) improvement of methods used
      to measure depth of submucosal invasion in the Ip type; (5) Japanese
      morphological classification of colorectal neoplastic lesions in terms of the
      clinical pathology and genetics of laterally spreading tumors; (6) villous
      tumors.

PMID- 19153490
TI  - Caught up with time.

PMID- 19153491
TI  - Cystic nonfunctioning pancreatic endocrine neoplasm presenting communication with
      main pancreatic duct.

PMID- 19153492
TI  - Increased risk of anastomotic leakage with diclofenac treatment after
      laparoscopic colorectal surgery.
AB  - BACKGROUND: Over a period our department experienced an unexpected high frequency
      of anastomotic leakages. After diclofenac was removed from the postoperative
      analgesic regimen, the frequency dropped. This study aimed to evaluate the
      influence of diclofenac on the risk of developing anastomotic leakage after
      laparoscopic colorectal surgery. METHODS: This was a retrospective case-control
      study based on 75 consecutive patients undergoing laparoscopic colorectal
      resection with primary anastomosis. In period 1, patients received diclofenac 150
      mg/day. In period 2, diclofenac was withdrawn and the patients received an opioid
      analgesic instead. The primary outcome parameter was clinically significant
      anastomotical leakage verified at reoperation. RESULTS: 1/42 patients in the no
      diclofenac group compared with 7/33 in the diclofenac group had an anastomotic
      leakage after operation (p = 0.018). In a multivariate regressional analysis,
      none of the recorded factors were significantly associated with the frequency of
      anastomotical leakages when diclofenac treatment was omitted from the model.
      CONCLUSIONS: We found an increased number of clinically significant anastomotic
      leakages in patients receiving oral diclofenac for postoperative analgesia. There
      is an urgent need to test our hypothesis in prospective randomized clinical
      trials and to examine whether our findings can be extended to open surgery and to
      other NSAIDs.

PMID- 19153493
TI  - Clinical characteristics of gastric cancer associated with pregnancy.
AB  - BACKGROUND/AIMS: This study was conducted to evaluate the clinical features and
      treatment outcome of gastric cancer associated with pregnancy. METHODS:
      Clinicopathologic characteristics of 15 patients who were diagnosed as having
      gastric cancer during pregnancy or within 1 year after delivery (the P-related
      group) were compared with those of 53 age-matched pregnancy-unrelated gastric
      cancer patients (the control group). RESULTS: Significant differences were found
      in tumor stage and surgical curability; the numbers of stage IV disease were 12
      (80%) and 21 (40%; p = 0.006), and those of curative resection were 4 (27%) and
      20 (62%; p = 0.02) in the P-related and the control group, respectively. Three
      year survival rate was significantly lower in the P-related group (23.3%) than in
      the control group (52.8%; p = 0.007). In the P-related group, only 3 patients,
      including one patient diagnosed using endoscopy, survived without recurrences. In
      the multivariate analysis, pregnancy was not identified as an independent risk
      factor associated with poor outcome. CONCLUSION: Gastric cancer associated with
      pregnancy is discovered at its advanced stage and consequently shows a dismal
      prognosis. Considering that the patients who underwent curative resection have a
      favorable prognosis, primary efforts should be focused on early diagnosis.

PMID- 19153494
TI  - A case of amyoplasia in a monochorionic twin pregnancy: a sequela from twin-twin
      transfusion syndrome?
AB  - OBJECTIVE: To present and discuss the sonographic and clinical findings in one
      twin of a monochorionic pair affected by amyoplasia. METHODS: On ultrasound
      examination at 21 weeks in a monochorionic twin pregnancy, twin I was smaller,
      hydropic, with multiple contractures consistent with amyoplasia and
      oligohydramnios. Twin II was anatomically normal with polyhydramnios. RESULTS:
      The twins were delivered at 28 weeks' gestation. The clinical findings were
      consistent with twin-twin transfusion syndrome (TTTS). CONCLUSION: It is
      postulated that TTTS may be a causative factor in the excessive incidence of
      amyoplasia in monozygotic twin pregnancy.

PMID- 19153495
TI  - 2009--Building on our achievements.

PMID- 19153496
TI  - Ectopic fat deposition and the metabolic syndrome in obese children and
      adolescents.
AB  - AIMS: We examined the impact of varying degrees of obesity on the prevalence of
      the metabolic syndrome and its relation to ectopic fat deposition in a large,
      multi-ethnic cohort of children and adolescents. METHODS: A standard glucose
      tolerance test was administered to 438 obese, 31 overweight and 20 nonobese
      children and adolescents. Baseline measures included blood pressure and plasma
      lipid and insulin levels. In a subset of 118 subjects, abdominal fat distribution
      was measured by magnetic resonance imaging (MRI) and further stratified into
      tertiles based on the proportion of abdominal fat in the visceral depot. Liver
      fat was measured by fast MRI and intramyocellular fat by proton magnetic
      resonance spectroscopy. RESULTS: Overall, the prevalence of the metabolic
      syndrome increased with the severity of obesity. In the subset of 118 obese
      adolescents undergoing MRI, there were no differences in age or body mass index z
      scores across tertiles. However, as the proportion of visceral fat increased,
      subcutaneous fat decreased. There were significant increases in the occurrence of
      hepatic steatosis, insulin resistance and metabolic syndrome, with subjects in
      tertile 3 being 5.2-times more likely to have the metabolic syndrome than those
      in tertile 1. CONCLUSIONS: The prevalence of the metabolic syndrome is high in
      obese children and adolescents and increases with worsening obesity. Obese
      adolescents with a high proportion of visceral fat and relatively low abdominal
      subcutaneous fat have a phenotype reminiscent of partial lipodystrophy: hepatic
      steatosis, profound insulin resistance and an increased risk of the metabolic
      syndrome.

PMID- 19153497
TI  - Primary aldosteronism.
AB  - BACKGROUND: Hypertension is one of the world's leading risk factors for morbidity
      and mortality. Most affected individuals have primary hypertension, while the
      most common cause of secondary hypertension is primary aldosteronism (6-10%).
      PRIMARY ALDOSTERONISM: Clinical manifestations include hypertension, hypokalemic
      alkalosis, renal dysfunction, nephrogenic diabetes insipidus, muscle weakness,
      paresthesias, tetany and, in severe cases, paralysis. The cardiovascular risks
      for patients with primary aldosteronism are greater than those for patients with
      primary hypertension. Compared with normotensive subjects, patients with primary
      aldosteronism have a 4.2-fold greater risk of stroke, a 6.5-fold greater risk of
      myocardial infarction and a 12.1-fold greater risk of atrial fibrillation.
      DIAGNOSIS: Patients with hypertension are screened for primary aldosteronism
      based on the plasma aldosterone to plasma renin activity ratio. A value >30
      constitutes a positive result. The diagnosis must be confirmed using one of four
      available aldosterone suppression tests. Lateralization of aldosterone
      hypersecretion is documented by adrenal venous sampling. MANAGEMENT: The
      foundation of primary aldosteronism management is normalization of circulating
      aldosterone and/or mineralocorticoid blockade. Optimal treatment of unilateral
      disease is adrenalectomy; spironolactone is the treatment of choice for bilateral
      disease.

PMID- 19153498
TI  - Is epigenetics an important link between early life events and adult disease?
AB  - BACKGROUND: Epigenetic mechanisms provide one potential explanation for how
      environmental influences in early life cause long-term changes in chronic disease
      susceptibility. Whereas epigenetic dysregulation is increasingly implicated in
      various rare developmental syndromes and cancer, the role of epigenetics in
      complex chronic diseases, such as cardiovascular disease, type 2 diabetes and
      obesity, remains largely uncharacterized. Extensive work in animal models is
      required to develop specific hypotheses that can be practicably tested in humans.
      ANIMAL MODELS: We have developed a mouse model showing that methyl donor
      supplementation prevents transgenerational amplification of obesity, suggesting a
      role for DNA methylation in the developmental establishment of body weight
      regulation. CONCLUSIONS: Coupling such models with recently developed epigenomic
      technologies should ultimately enable us to determine if epigenetics is an
      important link between early life events and adult disease.

PMID- 19153499
TI  - Recent progress in the genetics of diabetes.
AB  - BACKGROUND: Nearly 21 million people in the United States, or 7% of the
      population, are estimated to have diabetes. The incidence and prevalence of
      diabetes differ by ethnicity; however, both type 1 diabetes (T1D) and type 2
      diabetes (T2D) occur in all groups. The etiology of diabetes is multifactorial,
      involving both genetic and environmental factors. Advances in technology, leading
      to the identification of over a dozen candidate genes, have accelerated the
      search for genetic factors contributing to the risk of diabetes. To date,
      surprisingly little data exist to suggest there are common genetic pathways
      leading to development of T1D and T2D. These common forms of diabetes have
      complex genetic (and environmental) risk factors, making prediction and
      prevention difficult. Nonetheless, detection of diabetes susceptibility genes may
      facilitate identification of novel pathways that can serve as therapeutic targets
      and lead to disease prevention.

PMID- 19153500
TI  - Metabolic journey to healthy longevity.
AB  - BACKGROUND: The process of aging is associated with progressive remodeling. The
      age-dependent remodeling process mainly affects anthropometrics and endocrine
      function, which subsequently impact metabolic factors. In some individuals, e.g.,
      the very select group of healthy centenarians, the remodeling process is
      successful. The reasons why centenarians are able to reach the extreme limits of
      human life span are still largely unknown; however, several studies in humans
      have shown that longevity is associated with a significant improvement in glucose
      handling - mainly, a rise in insulin sensitivity and a decline in plasma insulin
      like growth factor I levels. CONCLUSIONS: Caloric restriction seems to be the
      best positive modulator of metabolism to achieve longevity. Other specific
      metabolic adaptations, even those genetically induced, might also play a role in
      the health of centenarians.

PMID- 19153502
TI  - Pitfalls of insulin-like growth factor I assays.
AB  - BACKGROUND: Immunoassays that measure circulating concentrations of insulin-like
      growth factor I (IGF-I) are increasingly used to diagnose and monitor growth
      hormone (GH)-related diseases. Specifically, IGF-I measured by immunoassay is
      used to diagnose GH deficiency and acromegaly, and to monitor treatment efficacy
      in patients with acromegaly, particularly those treated with the GH receptor
      antagonist pegvisomant, as measurement of circulating GH is no longer suitable
      for monitoring disease activity. While techniques for measuring IGF-I have
      evolved over the decades, immunoassays are still the primary tool used in routine
      laboratories. Immunoassays depend on the interaction between antibodies and the
      analyte, and all factors that modify the accessibility of the epitopes recognized
      by the antibodies can influence results. With IGF-I assays, interference from
      binding proteins is an important variable affecting assay results. CONCLUSIONS:
      It is generally accepted that assay- and age-specific reference ranges are
      mandatory for meaningful interpretation of IGF-I concentrations. High-quality,
      method-specific reference ranges and a high degree of methodological consistency
      in the assay are essential for reliable comparison of results across studies and
      for long-term monitoring of individual patients.

PMID- 19153503
TI  - ACROSTUDY: Status Update on 469 Patients.
AB  - BACKGROUND: ACROSTUDY is an international noninterventional surveillance study
      open to all patients with acromegaly treated with the growth hormone antagonist
      pegvisomant. This web-based registry contains data reflecting actual clinical
      care of patients, and it is being used to monitor the long-term safety and
      efficacy of pegvisomant therapy for acromegaly. Since ACROSTUDY was launched in
      2004, there has been an increase in cumulative patient recruitment from 116
      patients in 2005 to over 500 by mid-2008. As of May 2008, over 300 centers in 10
      countries have contributed data from 469 patients. At the time of inclusion, 84%
      of patients had already been treated with pegvisomant. Of the 469 patients, the
      majority had received somatostatin analogue treatment (63% had received
      octreotide and 34% had received lanreotide); 20% reported no prior medical
      treatment. Overall, 74% had prior transsphenoidal surgery, 3% had undergone
      craniotomy and 35% had received radiation therapy (including stereotactic
      radiosurgery). Interestingly, 67% were treated with pegvisomant alone at study
      start, 4% took pegvisomant with a dopamine agonist, 26% with a somatostatin
      analogue and 3% took pegvisomant with both types of analogues. The starting dose
      of pegvisomant was 10 mg/day for 65% of patients treated with subcutaneous daily
      injections, and the mean insulin-like growth factor I (IGF-I) concentration at
      baseline was 526 ng/ml. Annual assessments since study launch in 2004 found 62
      78% of patients had normal IGF-I levels after 1-4 years of pegvisomant treatment
      at mean doses of 18.7-22 mg/day. Adverse events were reported for 13% of
      patients, including 6 serious adverse events considered possibly related to the
      drug. An increase in tumor size relative to the size at start of pegvisomant
      therapy was reported for 24 of the 469 patients (5.1%). Liver function test
      results more than twice the upper limit of normal were observed in 7.7%.
      CONCLUSIONS: Further analyses of the ACROSTUDY database will provide a better
      understanding of pegvisomant treatment in clinical practice.

PMID- 19153504
TI  - Insulin-like growth factor I and growth responses during the first year of growth
      hormone treatment in KIGS patients with idiopathic growth hormone deficiency,
      acquired growth hormone deficiency, turner syndrome and born small for
      gestational age.
AB  - BACKGROUND AND METHODS: We assessed the value of in- sulin-like growth factor I
      (IGF-I) monitoring during growth hormone (GH) treatment by retrospectively
      examining the relationships between (1) GH dose and IGF-I response, (2) baseline
      serum IGF-I concentration and growth response and (3) serum IGF-I response and
      growth response after 1 year of GH treatment among patients in the Pfizer
      International Growth Study database (KIGS). KIGS patients were eligible for the
      study if they were classified as having idiopathic GH deficiency, acquired GH
      deficiency, Turner syndrome or were born small for gestational age. RESULTS:
      Correlations between GH dose and IGF-I response and between pretreatment IGF-I
      values and first-year growth response were weak across all groups. Correlations
      between the IGF-I response and growth response after 1 year of treatment were
      greater than those between baseline serum IGF-I values and first-year growth
      response. Pre- and posttreatment clinical characteristics were consistently
      different across all groups, but the numerous technical factors affecting these
      relationships are remediable. CONCLUSIONS: IGF-I monitoring during GH therapy is
      a valuable tool to monitor compliance and ensure that IGF-I levels do not exceed
      the normal range for extended periods. IGF-I monitoring may help clinicians
      increase GH doses as needed during puberty to achieve normal serum IGF-I values
      and normal or enhanced growth.

PMID- 19153505
TI  - Use of recombinant human growth hormone in children with thalassemia.
AB  - BACKGROUND: Growth failure occurs in children with chronic anemias and, in
      particular, in approximately 30% of those with thalassemia. METHODS: We assessed
      recombinant human growth hormone (rhGH) use in a large cohort of children with
      thalassemia enrolled in the Pfizer International Growth Study Database (KIGS).
      RESULTS: We identified 147 short children with thalassemia who were treated with
      rhGH in KIGS. Of these, approximately 40% had a primary diagnosis of GH
      deficiency (GHD). They had low birth weight, short parents, reduced genetic
      height potential, low insulin-like growth factor I levels and delayed bone age.
      Treatment with rhGH for 1 year resulted in a significantly increased growth rate
      regardless of underlying GH or pubertal status. Although the resultant growth
      rates for thalassemic children were significantly higher than at baseline, they
      were less than those seen in similarly treated short children with or without
      GHD. CONCLUSIONS: GH testing should be performed in short thalassemic children,
      and those with GHD should be treated with rhGH. The value of rhGH therapy in
      short thalassemic children without GHD is less clear-cut and requires further
      study regarding final height outcome.

PMID- 19153507
TI  - Turner syndrome 2008.
AB  - BACKGROUND: Fetuses with prenatal diagnoses of 45,X Turner syndrome (TS) and
      abnormal fetal ultrasounds have poor prognoses for survival, but with modern
      medical management, those that do survive to birth may have good clinical
      outcomes. Fetuses with incidental diagnoses of mosaicism for 45,X associated with
      normal ultrasounds have a high survival rate and may have no or only mild
      features of TS. CURRENT GUIDELINES: At present, appropriate treatment for girls
      with TS may include growth-promoting therapy and pubertal induction with the dual
      aims of optimizing adult height and facilitating psychosocial adjustment. Current
      recommendations advocate mimicking normal physiology as much as possible, with
      use of microdose estradiol to initiate puberty. Healthcare providers should play
      a role in helping girls psychosocially adapt to ovarian failure. We now recognize
      there is an unacceptably high rate of premature mortality in adults with TS,
      mainly because of complications from congenital heart disease. Cardiac magnetic
      resonance imaging is recommended to screen for individuals at high risk for
      serious complications.

PMID- 19153508
TI  - Update on the role of aromatase inhibitors in growth disorders.
AB  - BACKGROUND: Without oestrogen action, the fusion of the growth plates is
      postponed and longitudinal growth continues for an exceptionally long period of
      time. Aromatase inhibitors that block oestrogen biosynthesis have therefore
      emerged as a new potential treatment option for children with short stature.
      Results from three prospective randomised controlled trials using potent third
      generation aromatase inhibitors have recently been published. These studies all
      show that treatment with the aromatase inhibitors letrozole and anastrozole
      effectively delays bone maturation and increases predicted adult height in boys
      with constitutional delay of growth and puberty (CDGP), idiopathic short stature
      and growth hormone deficiency. Long-term follow-up data from the study in which
      boys with CDGP were treated with letrozole for 1 year during adolescence suggest
      that the achieved gain in predicted adult height also results in taller final
      adult height. CONCLUSIONS: Until the safety profile of aromatase inhibitors,
      particularly their qualitative effects on bone development, is established, use
      of these agents must be considered experimental in treating short stature.

PMID- 19153509
TI  - Peripheral precocious puberty: causes and current management.
AB  - BACKGROUND: Peripheral precocious puberty (PPP) results from sex steroid exposure
      by a process other than activation of the hypothalamic-pituitary-gonadal axis. It
      is much less common than central precocious puberty and may be congenital or
      acquired. Causes of PPP range from well-characterized genetic mutations to those
      conditions without a known etiology (idiopathic). Medical evaluation and
      treatment of affected children is guided by the presenting features and ultimate
      diagnosis. CONCLUSIONS: Carefully executed and collaborative multicenter
      investigations are essential to expand our knowledge of the underlying
      pathophysiology, optimal therapy and ultimate outcomes in children with PPP.

PMID- 19153510
TI  - Introduction: unresolved issues in the management of children with idiopathic
      short stature.

PMID- 19153511
TI  - Optimizing growth hormone dosing in children with idiopathic short stature.
AB  - BACKGROUND: In the last 2 decades, recombinant human growth hormone (rhGH)
      therapy for children with idiopathic short stature (ISS) has demonstrated varying
      degrees of efficacy. Based on prediction models for this population developed
      from registry databases and extensive clinical experience, these differences have
      been attributed to age at diagnosis, dose of rhGH, parental height, treatment
      compliance, GH sensitivity, effectiveness of GH receptors, potency of the
      postreceptor signaling cascade, insulin-like growth factor I transcriptional and
      translational efficiency and epiphyseal responsiveness. CONCLUSIONS: Although
      there are no universally accepted biochemical criteria for determining when to
      initiate GH therapy for children with ISS, both molecular and biochemical factors
      may contribute to the success of therapy and play a significant role to maximize
      adult height.

PMID- 19153512
TI  - Management of idiopathic short stature: psychological endpoints, assessment
      strategies and cognitive-behavioral intervention.
AB  - BACKGROUND: In 2007, a Conference on Idiopathic Short Stature (ISS) endorsed the
      definition of ISS as a statistical (auxologic) rather than a medical (pathologic)
      deviation from the norm. Consequently, the ultimate criteria for evaluation of
      treatment in ISS shift from medical to psychological endpoints. OBJECTIVE: This
      review synthesizes empirical evidence of psychological outcomes in treated and
      untreated subjects with ISS, recommendations from the recent ISS Consensus
      Conference, theoretical concepts from pediatric psychology and rationales used
      for various intervention strategies to better evaluate and manage psychological
      endpoints in ISS in accordance with the Consensus Conference definition. METHODS:
      Different measures of psychological outcome in ISS are reviewed to explain
      apparent heterogeneity among empirical study findings. Key issues include: (1)
      adaptation to major stressors associated with short stature (e.g., bullying, peer
      relations) and the correlation of adaptation failure with low socioeconomic
      status and impaired quality of life in adulthood; (2) development of valid and
      sensitive assessment tools; (3) clinical decision-making based on psychological
      assessment, ethical principles concerning informed consent and expectation of
      benefit from psychological treatment and (4) intervention approaches including
      counselling, cognitive-behavioral therapy, assertiveness training and growth
      hormone therapy. CONCLUSIONS: There are different but complementary strategies
      for medical and psychological enhancement of psychosocial outcome in subjects
      with ISS.

PMID- 19153513
TI  - Preserving fertility in prepubertal children.
AB  - BACKGROUND: As a result of advances in treatment, almost 80% of children and
      adolescents who currently receive a diagnosis of cancer become long-term
      survivors. Potential adverse consequences of treatment include impaired puberty
      and fertility due to gonadal removal, genital tract injury or damage to germ
      cells from adjuvant therapy. In recent years, treatment of solid tumors and
      hematological malignancies has been modified in an attempt to minimize damage to
      the reproductive system. Simultaneously, advances in assisted reproductive
      technologies have led to new possibilities for the prevention and treatment of
      infertility. We review experimental data in animal models and clinical experience
      in adults and discuss strategies to preserve fertility in prepubertal children.
      CONCLUSIONS: Fertility preservation should now be considered in children facing
      cancer treatment that has a high risk of gonadal toxicity including high-dose
      chemotherapy and bilateral irradiation of the gonads at toxic doses.

PMID- 19153514
TI  - A 5-year-old boy with cryptorchidism and pubic hair: investigation and management
      of apparent male disorders of sex development in mid-childhood.
AB  - BACKGROUND: Late presentation of congenital adrenal hyperplasia as a 46,XX
      disorder of sex development due to 11-beta hydroxylase deficiency is uncommon.
      Such a case raises issues regarding appropriate investigation and management.
      CASE HISTORY: A 5-year-old boy who had recently moved to the United Kingdom
      presented at the endocrinology clinic with recurrent abdominal pain. He was
      normotensive and had a history of ambiguous genitalia since birth, a relatively
      small penis, bilateral cryptorchidism and pubic hair. A systematic workup
      revealed low anti-Mullerian hormone levels for age and sex and elevated serum
      testosterone, androstenedione and deoxycortisol levels. A urinary steroid profile
      confirmed a diagnosis of 11-beta hydroxylase deficiency. The child's karyotype
      was 46,XX. Further genetic analysis revealed a compound heterozygote mutation in
      the CYP11B1 gene. Ultrasound scan showed evidence of Mullerian structures and
      accumulation of menstrual blood in the vagina (haematocolpos). Following
      discussion at a multidisciplinary clinic, the patient did not undergo sex
      reassignment and subsequently proceeded to surgery for removal of the Mullerian
      structures. CONCLUSIONS: This case emphasizes the importance of a systematic
      approach to investigation of older children presenting with apparent male
      undermasculinisation. It also raises important issues about gender reassignment
      in mid-childhood and the indications for removal of Mullerian organs in a 46,XX
      boy.

PMID- 19153515
TI  - Two puzzling cases of thyroid dysgenesis.
AB  - BACKGROUND: In the last couple of years, different genes that play major roles in
      embryonic thyroid development have been identified. Several mutations, e.g.,
      NKX2.1, FOXE1 and PAX8, were identified in patients with congenital
      hypothyroidism due to thyroid dysgenesis. However, the pathophysiology of most
      cases of thyroid dysgenesis remains unknown. Due to the sporadic occurrence and
      discordance observed in monozygotic twins, a classic genetic hypothesis for
      thyroid dysgenesis is improbable. CASE REPORT: We present two pairs of
      monozygotic twins discordant for thyroid dysgenesis that exemplify these
      conceptual difficulties. CONCLUSIONS: Identification of the epigenetic
      differences observed in monozygotic twins discordant for thyroid dysgenesis may
      be crucial in discovering the pathogenesis of thyroid dysgenesis.

PMID- 19153517
TI  - Adrenocortical cancer treatment.
AB  - BACKGROUND: With a reported incidence of 1 to 2 cases per million, adrenocortical
      cancer (ACC) is a rare disease with poor prognosis. Age distribution shows two
      peaks: early childhood and between age 40 and 50 years, with females more
      frequently affected. Sequelae can include Cushing syndrome, virilization and
      hypertension or local symptoms consistent with abdominal obstruction. Although
      most cases of ACC are of sporadic origin, they may also occur as part of a
      congenital or familial disease in which the genetic abnormalities are well
      established. ACC can also be discovered incidentally in asymptomatic individuals.
      In sporadic ACC, some molecular modifications are commonly observed (i.e.,
      overexpression of insulin-like growth factor II or vascular endothelial growth
      factor and somatic mutations of tumor protein 53). When surgical resection of the
      tumor is impossible or ineffective, chemotherapy with etoposide, doxorubicin and
      cisplatin plus mitotane or with streptozotocin plus mitotane is frequently used;
      however, the overall survival rates are disappointing. CONCLUSIONS: Hormonal
      evaluation is essential to diagnose ACC and the prognosis depends on many
      factors. New treatments, such as insulin-like growth factor I receptor
      antibodies, tyrosine kinase inhibitors and other antiangiogenic compounds, are
      now being intensively investigated to identify better therapies for this
      extremely severe malignant neoplasia.

PMID- 19153518
TI  - Update on familial pituitary tumors: from multiple endocrine neoplasia type 1 to
      familial isolated pituitary adenoma.
AB  - BACKGROUND: Pituitary adenomas occur in a familial setting in about 5% of all
      cases and over half of these are due to multiple endocrine neoplasia type 1
      (MEN1) and Carney complex (CNC). Since the late 1990s, we have described non
      MEN1/CNC familial pituitary tumors that include all tumor phenotypes and have
      named this condition 'familial isolated pituitary adenoma' (FIPA). Clinical
      features of FIPA differ from those of sporadic pituitary adenomas in that
      patients with FIPA are often younger and have larger tumors at diagnosis. About
      15% of FIPA patients have mutations in the aryl hydrocarbon receptor interacting
      protein gene (AIP), which indicates that FIPA may have a diverse genetic
      pathophysiology. We review the clinical features of FIPA, the tumor pathologies
      found in this setting and the genetic/molecular data that have been recently
      reported. CONCLUSIONS: Clinically relevant pituitary adenomas are more common
      than previously thought and occur in a familial setting in about 5% of cases
      overall. Therefore, specific questioning regarding family history of pituitary
      disease should be part of the workup of all patients with pituitary adenomas, not
      just those with acromegaly. FIPA is a useful clinical framework to study the
      features of pituitary adenomas that occur in a familial setting since it
      encompasses all tumor phenotypes and heterogeneous/homogeneous expression among
      affected family members.

PMID- 19153519
TI  - New guidelines for the diagnosis of growth hormone deficiency in adults.
AB  - BACKGROUND: The task of diagnosing growth hormone deficiency (GHD) in adults is
      cumbersome because of the paucity of biological endpoints. Consequently, over the
      past decade different organizations have attempted to develop homogeneous
      criteria and methodology for worldwide use. GHD should be biochemically confirmed
      within an appropriate clinical context - but only if there is the intention to
      treat. Clinically, patients investigated for GHD should include those with signs
      and symptoms or a past history of hypothalamo-pituitary dysfunction and those
      with a history of cranial irradiation, tumour treatment, traumatic brain injury
      or subarachnoid haemorrhage. CONCLUSIONS: Subjects with >/=3 pituitary hormone
      deficiencies plus a low insulin-like growth factor I level do not need
      provocative testing. For those who must be tested, arguably the most commonly
      used provocative tests are the insulin tolerance test and the glucagon, GH
      releasing hormone (GHRH) + arginine and GHRH + GH-releasing hexapeptide tests.
      Cutoffs differ across tests and results may be influenced by gender, age, body
      mass index and the assay reference preparation.

PMID- 19153520
TI  - Treatment of growth hormone deficiency in adults.
AB  - BACKGROUND: The Growth Hormone Research Society held a Consensus Workshop in
      Sydney, Australia, in March 2007 to review advances in the management of growth
      hormone (GH) deficiency in adults and to update consensus recommendations.
      OBJECTIVE: This short review summarizes key background information presented at
      the workshop and the consensus recommendations that followed. CONCLUSIONS: The
      benefits of GH replacement in GH-deficient adults are evident throughout life.
      Clinical response to treatment should be assessed by monitoring biochemistry
      values, body composition and quality of life. There is no evidence that GH
      replacement increases the risk of tumour recurrence or de novo malignancy.

PMID- 19153521
TI  - Recent challenges in the diagnosis of Cushing's syndrome.
AB  - BACKGROUND: The diagnosis of Cushing's syndrome still represents a challenge for
      the endocrinologist. Correct implementation and interpretation of diagnostic
      procedures require expertise and a high degree of clinical knowledge. The
      diagnosis should be established based on results of two or more concordant first
      line tests (e.g., urinary free cortisol, midnight serum cortisol and low-dose
      dexamethasone testing); otherwise, second-line tests such as the dexamethasone
      suppressed corticotrophin-releasing hormone (CRH) test, desmopressin stimulation
      or later reevaluation can confirm/exclude the diagnosis. Aetiological diagnosis
      requires measurement of plasma corticotrophin (ACTH) to distinguish between ACTH
      dependent (pituitary or extrapituitary ACTH-secreting tumors) and ACTH
      independent Cushing's syndrome (adrenal cortisol-secreting lesions), and the
      possible detection of normal ACTH levels in patients with adrenal Cushing's
      syndrome must be kept in mind. Lastly, the differential diagnosis between
      pituitary and ectopic ACTH secretion can be performed using CRH testing, high
      dose dexamethasone suppression and inferior petrosal sinus sampling. CONCLUSIONS:
      The different epidemiology of the two entities and the incomplete diagnostic
      accuracy of diagnostic procedures mandate careful evaluation of test results.

PMID- 19153523
TI  - Ghrelin and new metabolic frontiers.
AB  - BACKGROUND: A growing body of literature has profiled the complex identities and
      interactions of ghrelin analogues and their known and unknown receptors, which
      constitute the ghrelin system. In humans, acylated ghrelin (AG) induces a rapid
      rise in glucose and insulin levels. However, coadministration of unacylated
      ghrelin (UAG) counteracts this effect. Accumulating data support the existence of
      a specific receptor for UAG in addition to the corticotropin-releasing factor 2
      receptor and the growth hormone secretagogue type 1a receptor. Preclinically,
      mice that overexpress UAG exhibit decreased body weight, food intake, free fatty
      acid levels and fat pad mass weight and moderately decreased linear growth. In
      humans, intravenous infusion of UAG in normal subjects enhances the early insulin
      response to meals, improves glucose metabolism and insulin sensitivity and
      inhibits lipolysis. CONCLUSIONS: AG and UAG play an important regulatory role in
      metabolism.

PMID- 19153524
TI  - Bone and metabolism: a complex crosstalk.
AB  - BACKGROUND: Until recently, communication from metabolism to bone was considered
      purely unidirectional, involving complex interactions among an adipocyte-derived
      factor (leptin), the sympathetic nervous system and neuropeptides. However,
      studies in animal models now show that bone regulates glucose metabolism and fat
      mass via the uncarboxylated form of an osteoblast-derived factor (osteocalcin).
      These findings not only demonstrate that energy metabolism regulates bone
      remodeling through neural relays, but also that the skeleton acts as an endocrine
      tissue that regulates metabolic homeostasis. CONCLUSIONS: Further study is needed
      to understand the physiological role of these complex interactions in man and
      their implications for human diseases.

PMID- 19153526
TI  - Cushing's disease in dogs and humans.
AB  - BACKGROUND: Cushing's disease (CD) is a common endocrinological disorder in dogs
      with an estimated incidence of 1 to 2 cases/1,000 dogs/year. This is in contrast
      to humans in whom CD is rare. The clinical presentation of CD, however, is highly
      similar between dogs and humans, with characteristic signs, such as abdominal
      obesity, weight gain, fatigue, muscle atrophy and skin changes. Canine CD may
      therefore serve as an animal model for human CD, especially since therapeutic
      canine hypophysectomy can generate substantial amounts of primary corticotroph
      adenoma tissue for in vitro research purposes. In a recent study, we found that
      dopamine (DA) D(2) and somatostatin (SS) receptor subtypes are well expressed in
      canine corticotroph adenomas, but there are some distinct differences compared
      with the expression profile observed in human CD. These differences need to be
      considered when using canine CD as a model to evaluate the efficacy of novel
      DA/SS compounds for potential use in human CD. CASE REPORT: This case involves an
      8-year-old female dog that developed signs of exercise intolerance, muscle
      weakness and polyuria/polydipsia due to an adrenocorticotropic hormone-secreting
      pituitary adenoma. The dog underwent curative transsphenoidal hypophysectomy and
      has remained in complete remission in the 3.5 years since surgery.

PMID- 19153527
TI  - Endocrine diseases in animals.
AB  - BACKGROUND: Several endocrine disorders that affect humans also occur as
      endocrinopathies in companion animals. Spontaneous endocrine disorders in animals
      may provide valuable information for their counterparts in human endocrinology.
      For example, the discovery of progesterone-induced growth hormone production in
      the mammary gland of dogs may have important consequences for understanding the
      pathogenesis of breast cancer in women. In addition, the majority of diabetic
      cats have a type of diabetes mellitus that closely resembles type 2 diabetes
      mellitus in humans and therefore may serve as an animal model for this disease in
      humans. This review describes several endocrine diseases in companion animals
      that are quite similar to those in humans and emphasizes their usefulness as
      spontaneous animal models for human endocrine disorders.

PMID- 19153530
TI  - Endoscopic repair of supraorbital ethmoid cerebrospinal fluid leaks.
AB  - OBJECTIVE: To examine the clinical and anatomical characteristics of patients
      with supraorbital ethmoid (SOE) cerebrospinal fluid (CSF) leaks and
      encephaloceles and identify specific considerations unique to their management.
      METHODS: Retrospective review of patients who underwent repair of SOE CSF leaks
      at our institution from 2003 to 2007. RESULTS: The majority of patients were
      women (5/8), middle-aged (mean: 54.9 years) and had a high body mass index (mean
      42.3). Intracranial pressures (ICPs) were elevated in 6/8 patients. Anatomically,
      6/8 patients had defects medial to the medial orbital wall (MOW; mean distance:
      4.15 mm) and 2/8 had defects lateral to the MOW (mean distance: 8.14 mm). Seven
      out of 8 were successfully repaired endoscopically, and 1 patient with a lateral
      defect required an adjunctive trephination. CONCLUSIONS: Patients with
      spontaneous SOE CSF leaks have unique clinical characteristics that include
      obesity and elevated ICP. Extension of a skull base defect lateral to the MOW and
      a narrow anterior-posterior diameter of the frontal recess are technical
      obstacles to endoscopic repair and may necessitate an adjunctive external
      approach.

PMID- 19153531
TI  - Human basophils and cytokines/chemokines.
AB  - Basophils comprise the smallest population in human peripheral blood leukocytes.
      The role of basophils in the pathogenesis of allergic diseases has long been
      obscure, although their accumulation and activation in tissues have suggested
      their potential importance. Recent advances in the field of basophil biology have
      indicated that cytokines and chemokines are the primary regulators of basophil
      functions. In addition, various functions of these cells seem differently
      modulated. The evidence strongly supports the notion that basophils exposed to
      these substances and allergens will behave as unique effector cells that
      presumably play proinflammatory roles in type I allergic reactions.

PMID- 19153532
TI  - New insights into the roles for basophils in acute and chronic allergy.
AB  - Basophils represent less than 1% of peripheral blood leukocytes. They are often
      recruited to the site of allergic inflammation, albeit in small numbers. However,
      it remained uncertain whether basophils play any significant role in allergic
      reactions or act as minor and redundant 'circulating mast cells'. We have
      recently demonstrated that basophils play critical roles in systemic anaphylaxis
      and chronic allergic inflammation, distinctively from mast cells. Basophils are
      one of the major players in the IgG- but not IgE-mediated systemic anaphylaxis,
      in contrast to mast cells. In response to the allergen-IgG immune complexes,
      basophils release the platelet-activating factor rather than histamine as the
      major chemical mediator to induce the systemic anaphylaxis. The depletion of
      basophils protects mice from death due to anaphylactic shock. Basophils also play
      a crucial role in the development of the IgE-mediated chronic allergic
      inflammation with massive eosinophil infiltration in the skin, independently of T
      cells and mast cells, even though basophils account for only approximately 2% of
      the infiltrates. The basophil depletion shows a therapeutic effect on on-going
      allergic inflammation. Accumulating evidence suggests that basophils function as
      initiators rather than effectors of the chronic allergic inflammation. Thus,
      basophils and their products seem to be promising therapeutic targets for
      allergic disorders.

PMID- 19153533
TI  - Origin of basophils and mast cells.
AB  - Basophils and mast cells are major players in the progression of allergic
      disorders. Although both cell types originate from hematopoietic stem cells,
      their lineage commitment pathways and mechanisms have been unsolved issues in
      hematology. Recent advances in the multicolor FACS system enable the prospective
      isolation of progenitor populations whose readouts are restricted to basophil
      and/or mast cell lineages. These newly-isolated progenitor subsets are helpful to
      understand the developmental machinery of basophil and mast cell lineages,
      leading to the possible exploitation of a novel therapeutic strategy for allergic
      and autoimmune disorders. In this review, we summarize the recent progress in our
      understanding of the basophil/mast cell ontogeny on a cellular basis.

PMID- 19153534
TI  - Molecular mechanism of the additive effects of leukotriene modifier in asthmatic
      patients receiving steroid therapy.
AB  - BACKGROUND: The addition of leukotriene modifier (LM) may be a useful approach
      for uncontrollable asthma despite treatment with inhaled corticosteroid (ICS),
      especially in asthmatics comorbid with allergic rhinitis (AR), although little is
      known about its molecular mechanism. We evaluated the additive effects of LM with
      ICS on pulmonary function and airway inflammation in asthmatics with or without
      AR. METHODS: Eighteen uncontrolled steroid-treated asthmatics, nine with and nine
      without AR, were enrolled. Spirometry, peak expiratory flow (PEF) measurements,
      and exhaled breath condensate sampling were performed before and 8 weeks after LM
      administration. The lowest PEF over the course of one week, expressed as a
      percentage of the highest PEF (Min%Max PEF), was used as an index of fluctuation
      of the airway caliber. Airway cytokine expression was analyzed with a protein
      array. RESULTS: A significant improvement in forced expiratory volume in one
      second as a percentage of the predicted value (%FEV(1)) and Min%Max PEF was seen
      in the subgroup of asthma with AR. Although there was no significant difference
      in the baseline cytokine values between the groups, the exhaled RANTES level was
      significantly reduced by LM in the asthma with AR group. The changes in the
      RANTES level were significantly related to the changes in the %FEV(1) and Min%Max
      PEF values. CONCLUSIONS: LM caused a greater improvement in pulmonary function
      and airway inflammation in asthmatics with AR. The RANTES-mediated pathway may be
      involved in the improvement of the airflow limitation and airway lability by LM
      additive therapy in asthmatics receiving steroid therapy.

PMID- 19153535
TI  - Age-related changes of transforming growth factor beta1 in Japanese children.
AB  - BACKGROUND: Transforming growth factor beta1 (TGF beta 1) is an important factor
      in immunomodulation. The expression of TGF beta 1 has been shown to be influenced
      by the C-509T polymorphism in the TGF beta 1 gene. We investigated age-related
      changes of plasma TGF beta 1 levels in a birth-cohort study. In addition, the
      genotypes of the C-509T polymorphism were investigated in allergic and non
      allergic subjects. METHODS: Sixty-four neonates who met the following criteria
      were enrolled in this cohort study: 1) full-term vaginally delivery; 2) underwent
      DNA polymorphism analysis; and 3) questionnaire forms were filled out by parents
      at 0, 6 and 14 months of age. The umbilical cord blood at 0 months and peripheral
      blood at 6, and 14 months were collected. Plasma TGF beta1 levels were measured
      at 0, 6 and 14 months of age. Genomic DNA was extracted from their umbilical cord
      blood. The genotype of the subjects was examined for the presence of C-509T.
      RESULTS: The plasma TGF beta 1 level at 6 months was the highest of the 3
      measurements (at 0, 6, and 14 months of age). The TGF beta 1 levels at 14 months
      in allergic subjects were significantly higher than those in non-allergic
      subjects (p = 0.03). All subjects with bronchial asthma (n = 3) had the TT
      genotype of the C-509T polymorphism. CONCLUSIONS: The plasma TGF beta 1 levels
      change with age. In addition, TGF beta 1 may play a role in the pathogenesis of
      bronchial asthma.

PMID- 19153536
TI  - Activation of eosinophils by lipopolysaccharide-induced monocyte-derived
      cytokines.
AB  - BACKGROUND: Interactions between eosinophils and monocytes after
      lipopolysaccharide inhalation are yet to be investigated. The mechanism of
      eosinophil activation induced by lipopolysaccharide in the presence of monocytes
      was investigated. METHODS: Expression of ICAM-1 and Mac-1 on eosinophils was
      evaluated after lipopolysaccharide stimulation in the presence of monocytes or
      monocyte culture supernatants. Cytokines in the supernatant of lipopolysaccharide
      stimulated monocytes were measured using a cytokine array. RESULTS: Expression of
      ICAM-1 and Mac-1 on eosinophils was up-regulated after lipopolysaccharide
      stimulation in the presence of monocytes or monocyte culture supernatant.
      Lipopolysaccharide induced secretion of ENA-78, GMCSF, GRO, IL-1 beta, IL-6, IL
      10, MCP-1, TNF-alpha and MIP-3 alpha from monocytes. The up-regulation of ICAM-1,
      but not Mac-1, on eosinophils was attenuated by anti-TNF-alpha neutralizing
      antibody. CONCLUSIONS: Monocyte-derived TNF-alpha plays an important role in the
      up-regulation of ICAM-I on eosinophils induced by lipopolysaccharides.

PMID- 19153537
TI  - Various expression patterns of alpha1 and alpha2 genes in IgA deficiency.
AB  - BACKGROUND: IgA deficiency (IgAD) is the most common immunodeficiency, however
      the pathogenesis in most cases of IgAD is unknown. There are 2 subclasses of IgA,
      IgA1 and IgA2, and its heavy chains are encoded by 2 different genes, the alpha1
      and alpha2 genes. To investigate the molecular pathogenesis of IgA deficiency, it
      is important to evaluate each of the expressions of IgA1 and IgA2 separately.
      METHODS: In this study, we report on the reverse transcriptase (RT)-PCR method in
      which alpha1 and alpha2 mRNAs can be separately evaluated. This method is based
      on electrophoretic separation using the difference of 39 bases between alpha1 and
      alpha2 mRNAs. Three selective, 5 partial and 2 secondary IgAD patients were
      examined. RESULTS: In the 3 selective IgAD patients, no alpha1 or alpha2 mRNA
      expression was detected. In the 5 partial IgAD patients, various alpha1 and
      alpha2 mRNA expression patterns were found. One of the partial IgAD patients
      showed only alpha2 gene expression, but not alpha1 gene expression, and was found
      to show an alpha1 gene deletion together with gamma 2 and epsilon gene deletions.
      His plasma IgA2 level was within the normal range. CONCLUSIONS: Patients with an
      alpha1 gene deletion can be considered as having partial IgAD. Using this method,
      we identified the second case of alpha1 gene deletion in Japan, and classified
      IgAD patients on the basis of alpha1 and alpha2 expression.

PMID- 19153538
TI  - Aging exacerbates restraint stress-induced inhibition of antigen-specific
      antibody production in mice.
AB  - BACKGROUND: We have recently found that exposure to acute restraint stress
      suppresses antigen-specific antibody production, including IgE, in a murine model
      of allergic rhinitis. Although age-related alterations in immune responses are
      known, it remains unclear whether aging modulates the antibody production under
      stressful conditions. In this study, we set out to determine the effects of aging
      on antibody production under acute restraint stress in mice. METHODS: Both young
      and aged CBA/J mice were repeatedly sensitized intranasally with phospholipase A2
      (PLA2) without adjuvants. Restraint stress was applied using uniform cylinders
      once a week for a continuous 8h period, on 5 occasions in total. Blood samples
      were taken at 0, 20 and 30 days after primary sensitization, and production of
      PLA2-specific antibodies and levels of IL-4, IFN-gamma, IL-10 and IL-1 beta in
      sera were determined by ELISA. RESULTS: Repeated intranasal sensitization with
      PLA2 induced PLA2-specific IgE, IgG1 and IgG2a production in aged mice. We found
      that exposure to restraint stress significantly inhibited production of PLA2
      specific IgE, IgG1 and IgG2a in aged mice. In addition, antibody production under
      restraint stress decreased significantly in aged mice when compared with young
      mice. No IL-4, IFN-gamma, IL-10 or IL-1 beta were detected in sera from non
      stressed or stressed aged mice. CONCLUSIONS: Aging exacerbates the
      immunosuppressive role of acute restraint stress in antigen-specific antibody
      production in mice.

PMID- 19153539
TI  - Enhanced goblet cell hyperplasia in HDC knockout mice with allergic airway
      inflammation.
AB  - BACKGROUND: Histamine is known to have immunoregulatory roles in allergic
      reactions through histamine receptor 1 (H1R), H2R, H3R and H4R. However, its role
      in goblet cell hyperplasia in the airways of asthma patients is yet to be
      clarified. OBJECTIVE: This study was designed to examine the role of histamine in
      goblet cell hyperplasia using histamine-deficient mice (Hdc-/- mice) with
      allergic airway inflammation. METHODS: Wild-type and Hdc-/- C57BL/6 mice were
      sensitized with ovalbumin (OVA). After a 2-week exposure to OVA, goblet cell
      hyperplasia was evaluated. Cell differentials and cytokines in BALF were
      analyzed. The mRNA levels of MUC5AC and Gob-5 gene were determined
      quantitatively. RESULTS: The number of eosinophils in BALF increased in both the
      sensitized wild-type mice and Hdc-/- mice with OVA inhalation. In addition, the
      numbers of alveolar macrophages and lymphocytes in BALF increased significantly
      in the sensitized Hdc-/- mice with OVA inhalation compared to the wild-type mice
      under the same conditions. The concentrations of Interleukin-4 (IL-4), IL-5, IL
      13, Interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and IL
      2 in the BALF all increased significantly in both groups compared to those
      exposed to saline. In particular, the concentration of TNF-alpha in the Hdc-/-
      mice exposed to OVA was significantly higher than that in the wild-type mice
      under the same conditions. The mRNA levels of Gob-5 and MUC5AC, and the ratio of
      the goblet cells in the airway epithelium significantly increased in Hdc-/- mice
      exposed to OVA compared to wild-type mice. CONCLUSIONS: These results suggested
      that histamine may play a regulatory role in goblet cell hyperplasia in allergic
      airway inflammation.

PMID- 19153540
TI  - Acute allergic reaction due to milk proteins contaminating lactose added to
      corticosteroid for injection.
AB  - We encountered two patients with severe cow's milk allergy who reacted strongly
      to an injection of methylprednisolone sodium succinate (Sol-Medrol 40 mg Pfizer,
      Japan). They came to our hospital because of an asthmatic attack or urticaria and
      were treated with Sol-Medrol 40 mg. After the injection, the allergic reaction
      was immediate. Skin prick tests demonstrated that the beta-lactoglobulin
      contaminating the lactose of the drug preparation caused the immediate allergic
      reaction.

PMID- 19153541
TI  - Use of the DISCERN instrument by patients and health professionals to assess
      information resources on treatments for asthma and atopic dermatitis.
AB  - BACKGROUND: As patients share in the decision-making process regarding treatments
      they receive, it is important that they can discriminate between reliable and
      unreliable sources of information about potential treatments. METHODS: In this
      study, health professionals and patients were asked to assess the reliability of
      information contained in pamphlets on treatments for asthma and atopic dermatitis
      using a new Japanese translation of an instrument called DISCERN. The scores
      given by both groups were analyzed to assess inter-rater agreement. The same
      DISCERN instrument was used by health professionals to evaluate websites on
      treatments for atopic dermatitis and the degree of inter-rater agreement was
      assessed again. RESULTS: There was a greater inter-rater agreement between health
      professionals than between patients. When health professionals used the
      instrument to evaluate websites, the final rankings given were consistent between
      different raters, showing good inter-rater agreement. CONCLUSIONS: We conclude
      that DISCERN is useful for evaluating the reliability of medical information both
      in pamphlets and on the internet, although it is used more effectively by health
      professionals than by patients. Further studies are needed on the use of DISCERN
      by patients in evaluating websites containing medical information.

PMID- 19153542
TI  - Cost analysis and sociomedical aspects of the conservative and surgical treatment
      of hip osteoarthritis.
AB  - INTRODUCTION: Hip osteoarthritis (OA) is one of the most common causes of pain,
      physical disability and marked impairment of patients' physical fitness and
      mobility. Insufficient funding for health care contributes to prolonged waiting
      times for total hip replacement (THR) surgery, which has been proven to be the
      only effective treatment for OA. Average waiting time in Poland is estimated at 2
      2.5 years. Objective. To carry out a retrospective comparative analysis of the
      cost of THR surgery vs. conservative treatment for OA in a variety of
      sociomedical aspects while patients are awaiting THR. MATERIAL AND METHODS: Two
      groups of patients were compared. Group I consisted of 77 patients awaiting THR
      and treated with physical therapy and drugs. Group II consisted of 91 patients
      who underwent THR. Evaluations and comparisons were based on a modified WOMAC
      index, the SF-8 survey and estimates of pharmacological, procedural and
      orthopaedic equipment expenditures. RESULTS: Prolonged waiting times and the
      associated conservative treatment costs, including drugs, physical therapy,
      sanatorium, orthopaedic equipment, transport, sickness benefits and costs of
      pharmacological treatment of complications, were shown to be approximately twice
      higher compared to the cost of surgical treatment. Apart from financial costs,
      other significant aspects should also be noted, such as deterioration of the
      patient's life quality and psychosocial health, and prolonged anguish.
      CONCLUSIONS: Pharmacological treatment, rehabilitation, physical therapy and
      other methods appear to be inefficient in patients with hip OA awaiting THR and
      their costs are twice as high. Additionally, NSAID drugs produce GI ulcers in 25%
      of the patients. Psychosocial problems are also common for these patients.
      Surgical treatment produces a radical improvement of the quality of life and
      ameliorates psychosocial problems. Therefore, hip OA costs can only be reduced by
      shorter waiting times, which can be accomplished through an increase in funding
      resulting in wider access to the procedure.

PMID- 19153543
TI  - Clinical and functional profile of patients with the Painful Shoulder Syndrome
      (PSS).
AB  - BACKGROUND: The Painful Shoulder Syndrome (PSS) is characterized by varying
      degrees of pain and functional limitation. The aim of this study is to describe
      the clinical and functional profile of these patients. MATERIAL AND METHODS: 136
      patients undergoing clinical treatment for PSS were evaluated by a questionnaire
      regarding the following variables: sex, age, occupation, affected shoulder and
      its dominance, image diagnosis, pain location, intensity and characteristics,
      physical activity involving the shoulder, preferential position of upper limbs
      during occupational activity, limitation of movements during activities o daily
      living, and job absenteeism. RESULTS: 74.3% of the patients were women (p<0.001),
      and 54.4% were at or below the mean age of 50+/-12.5 years. The right shoulder
      was affected most frequently (58.8%) and dominant (91.9%). Rotator cuff tear was
      the most frequent shoulder pathology (75.4%). Treatment was sought more commonly
      in the chronic stage of pain (61.0%). Pain, moderate in intensity, predominated
      in males (54.3%) and severe pain was more frequent in females (47.5%), restricted
      to the shoulder in 44.1% and worsening at night (50%). The upper limbs were used
      more frequently below shoulder level during usual daily activities (68.4%), and
      limitation of movements was present mainly in women (63.4%, p=0.017). CONCLUSION:
      Rotator cuff tear is the most frequent cause of PSS. PSS produces pain and
      functional limitation, especially in women.

PMID- 19153544
TI  - Analysis of three-dimensional motion of the glenohumeral joint in impingement
      syndrome.
AB  - INTRODUCTION: Impingement syndrome (IS) is one of the most common causes of
      progressive dysfunctions of the shoulder joint. The aim of the study was to
      evaluate the changes in the joint's mobility in patients with IS and to find
      correlations between the angular values of particular motion ranges. MATERIAL AND
      METHOD: The study involved 58 people aged 24-85 years, treated for IS from 2004
      to 2006. The average duration of the disease was 40 months. A comparative
      examination of active mobility on the healthy and affected side was carried out
      according to the SFTR method. RESULTS: A comparison of mean values of the motion
      ranges indicated significant limitations of active mobility in the affected
      shoulder. The greatest mobility deficit was found in the external rotation range.
      Moreover, there was a statistically significant correlation between the angular
      values of internal rotation and the values of the remaining motion ranges.
      CONCLUSIONS: Impingement syndrome.

PMID- 19153546
TI  - Per-operative vibration analysis: a valuable tool for defining correct stem
      insertion: preliminary report.
AB  - BACKGROUND: Defining the stem insertion end point during total hip replacement
      still relies on the surgeon's feeling. When a custom-made stem prosthesis with an
      optimal fit into the femoral canal is used, the risk of per-operative fractures
      is even greater than with standard prostheses. Vibration analysis is used in
      other clinical settings and has been tested as a means to detect optimal stem
      insertion in the laboratory. The first per-operative use of vibration analysis
      during non-cemented custom-made stem insertion in 30 patients is reported here.
      MATERIALS AND METHODS: Thirty patients eligible for total hip replacement with
      uncemented stem prosthesis were included. The neck of the stem was connected with
      a shaker that emitted white noise as excitation signal and an impedance head that
      measured the frequency response. The response signal was sent to a computer that
      analyzed the frequency response function after each insertion phase. A technician
      present in the operating theatre but outside the laminated airflow provided feed
      back to the surgeon. RESULTS: The correlation index between the frequency
      response function measured during the last two insertion hammering sessions was
      >0.99 in 86.7% of the cases. In four cases the surgeon stopped the insertion
      procedure because of a perceived risk of fracture. Two special cases illustrating
      the potential benefit of per-operative vibration analysis are described.
      CONCLUSIONS: The results of intra-operative vibration analysis indicate that this
      technique may be a useful tool assisting the orthopaedic surgeon in defining the
      insertion endpoint of the stem. The development of a more user-friendly device is
      therefore warranted.

PMID- 19153545
TI  - Intramedullary osteosynthesis with gamma nail in treatment of peritrochanteric
      fractures of the femur.
AB  - INTRODUCTION: The treatment of peritrochanteric fractures of the femur,
      particularly in elderly people is a therapeutic challenge for the surgeon, not
      only due to the patient's age but also the type of fracture. The aim of the
      present paper is to assess the efficacy of closed intramedullary osteosynthesis
      with a gamma nail in the treatment of peritrochanteric fractures depending on the
      type of fracture and patient age. MATERIAL AND METHODS: The study involved 109
      patients treated at the Orthopaedic and Trauma Department of A. Sokolowski
      Hospital in Walbrzych in 2006. The mean age of the patients was 72 years (range
      15-95). The follow-up period was 6-20 months, 15 months on average. A detailed
      assessment involved 97 patients aged 50 years and older. The study utilised AO
      and Kyle's classifications of fractures; the criteria of Golec and the 27th
      Congress of the Polish Society of Orthopaedics and Traumatology (PSOT) were used
      for radiographic assessment; and the Harris scale was used for functional
      assessment. RESULTS: According to the standards of radiographic assessment, 75%
      of patients had excellent and good results, indicating good mechanical efficacy
      of intramedullary fixation and good fracture consolidation. According to the
      Harris scale, 13% of the patients achieved poor scores in the functional
      assessment. The poor results were related to the age of the patients and co
      existing general diseases rather than to the degree of fracture instability.
      CONCLUSIONS: In stable peritrochanteric fractures of the femur, intramedullary
      gamma nailing was associated with good and excellent results irrespective of the
      patient's age. Poorer functional results in patients aged 71 or older were due to
      poorer pre-injury general health and local status of the patient.

PMID- 19153547
TI  - Estimation of vastus medialis' excitability in cases of lateral patellar
      instability in children.
AB  - BACKGROUND: The aim of this study was to evaluate the excitability of the vastus
      medialis muscle in children with lateral patellar instability, because it is
      assumed that, apart from restoring the elasticity of passive lateral restraints,
      the main goal of rehabilitation of this dysfunction is strengthening of the
      vastus medialis. MATERIALS AND METHODS: Measurements were done in 56 patients
      (mean age 15.9 years) in the study group and 38 patients (mean age 15.2 years) in
      the control group. The study was carried out from October 2006 to April 2007.
      Neuro-muscular-excitability was assessed by determining rheobase. A Sonopuls 992
      apparatus was used for this purpose. RESULTS: 72 measurements were taken in the
      study group, with a mean value of rheobase of 15.3 mA(+/-4.9). In the control
      group, 76 measurements were taken and the mean value of rheobase was 11.5 mA(+/
      4.1). CONCLUSIONS: 1. Vastus medialis muscles in children with lateral patellar
      instability display significantly higher mean values of rheobase in comparison to
      mean values from the control group, i.e they are less excitable. Consequently,
      measuring rheobase in the vastus medialis in children with lateral patellar
      instability is an objective method for the assessment of treatment and
      rehabilitation outcomes. 2. Strengthening the vastus medialis muscle, the only
      active medial stabilizer of patella, is one of the most important elements of
      rehabilitation in children with signs of lateral patellar instability because it
      has lower excitability in these children than in healthy children.

PMID- 19153548
TI  - New trends in the treatment of osteogenesis imperfecta type III - own experience.
AB  - INTRODUCTION: Osteogenesis imperfecta (OI) is a genetic disorder caused by a
      mutation in the genes that encode the chains of type I collagen. Clinical
      manifestations include increased bone fragility and blue sclerae. OI type III is
      the most severe form with fractures occurring already in utero. Fracture
      immobilisation and orthopaedic surgery are the mainstay of treatment for patients
      with OI, and are combined with rehabilitation and bisphosphonate therapy.
      PATIENTS AND METHODS: The study involved 8 children with osteogenesis imperfecta
      type III, aged 1 month to 6 years. All of them were treated with cyclic
      intravenous infusions of pamidronate. Laboratory studies conducted before and
      after each 3-day cycle of pamidronate therapy included complete blood count,
      serum calcium, phosphorus, magnesium, osteocalcin, and calcium/creatinine index
      in morning urine and collagen type I cross-linked N-telopeptide (NTx). Infant
      total body densitometric scans were obtained in 5/8 patients. RESULTS: Patients
      were treated for periods of 3-58 months. Fracture rates decreased with treatment
      in all patients compared to the prenatal period. Pamidronate also slowed down
      bone turnover, and particularly the resorption rate. The most common side effects
      during treatment included hypocalcaemia (7/8 patients) and fever (up to 39
      degrees C) after the first cycle of treatment. CONCLUSION: Symptomatic
      bisphosphonate therapy in children with osteogenesis imperfecta ameliorated the
      clinical course (decreased bone pain and reduced incidence of fractures).
      Pamidronate therapy had a positive impact on functional parameters such as
      independence in everyday activities and better mobility. The treatment was safe.

PMID- 19153549
TI  - Evaluation of bone mineral density and bone metabolism in children with multiple
      bone fractures.
AB  - BACKGROUND: The aim of the study was to carry out a comprehensive analysis of
      determinants of multiple bone fractures in children with regard to densitometric
      indices and markers of bone metabolism. MATERIAL AND METHODS: The study involved
      112 children aged 5-18 years, including 81 patients with a history of at least 3
      bone fractures and 31 healthy patients in a control group. Total body and spinal
      DXA densitometry of the skeleton (DPX-L apparatus, Lunar) was carried out in all
      children. Laboratory assays comprised the determination of calcium, phosphorus,
      magnesium (in the serum and 24-hour urine collection), parathormone, liver
      metabolite of vitamin D, osteocalcin, bone alkaline phosphatase, and N-terminal
      cross-linked telopeptide of collagen type I (NTx). RESULTS: Mean values of DXA Z
      score, both in total body and in spinal scans, were significantly lower in
      children with multiple fractures as compared to controls. In children with
      multiple fractures, there was a higher prevalence of hypercalciuria,
      hypermagnesuria and hyperphosphaturia. Decreased levels of the liver metabolite
      of vitamin D were observed in 20/81 (24.7%) patients in this group and in 6/31
      controls. Other findings included a higher level of NTx in 38/75 (50.7%) patients
      with fractures, an increased activity of bone alkaline phosphatase in 29, and of
      osteocalcin in 12 patients. In this group, there was a significant negative
      correlation between biochemical bone turnover markers and low bone mass. Also,
      lower DXA Z-scores were found in children with higher urinary calcium excretion.
      CONCLUSIONS: 1. Decreased bone mineral density was the most frequent risk factor
      for bone fractures in children; it was found in about 2/3 of the patients with
      multiple bone fractures. 2. Accelerated bone turnover, and, particularly,
      increased bone resorption, indicates a derangement of bone metabolism in children
      with multiple fractures. 3. Repeated fractures during the body growth period are
      an indication for a quantitative evaluation of bone mass, calcium-phosphate
      metabolism and bone turnover markers.

PMID- 19153550
TI  - Diagnostic difficulties in pigmented villonodular synovitis. Presentation of
      cases.
AB  - Pigmented villonodular synovitis is a rare entity. There are limited and diffuse,
      intra- and extraarticular forms. In the literature, this condition has been
      called xanthoma, xanthogranuloma, villous arthritis, pigmented villonodular
      synovitis, xanthomatous giant cell tumour, giant cell tumour of tendon sheath,
      giant cell fibrohemangioma, benign synovioma. The paper presents two cases in
      which, due to ignorance of this disease, patients were primarily qualified for
      oncological treatment: chemotherapy and radical resection or limb amputation. In
      both cases synovectomy produced good clinical outcomes although the procedures
      were not radical. It is necessary to unify the naming of pigmented villonodular
      synovitis because various names can be misunderstood by clinicians.
      Investigations indicating a non-inflammatory aetiology and reports of potential
      malignancy suggest that the terms inflammation or synovitis should no longer be
      used.

PMID- 19153551
TI  - Difficult removal of an epidural catheter in a postpartum woman.

PMID- 19153552
TI  - Recombinant human activated protein C and strict glycemic control in sepsis:
      mutually exclusive strategies?

PMID- 19153554
TI  - Non-invasive ventilation outside the Intensive Care Unit for acute respiratory
      failure: the perspective of the general ward nurses.
AB  - BACKGROUND: The introduction of non-invasive ventilation outside the Intensive
      Care Unit (ICU) is an increasing phenomenon, motivated by the shortage of
      intensive care beds and growing confidence with the technique. However, although
      general ward nurses are responsible for carrying out the daily management of the
      treatment and the extra monitoring it requires, their perspective on non-invasive
      ventilation (NIV) has never before been studied, and as a result their training
      is often neglected. METHODS: A questionnaire was administered to the nurses of
      four non-intensive wards. The questionnaire addressed several issues, including
      the extent of the nurses' involvement in the decision to start the treatment,
      their relationship with the ward physicians and the Medical Emergency Team (MET),
      the monitoring, incidence, and management of errors and complications, the
      adhesion to the prescribed ventilatory program, and the desired training.
      RESULTS: Out of 115 nurses, 90 completed the questionnaire (78.3%). Of this
      group, 67% did not feel involved in the decision-making process, and half felt
      they were inadequately informed. Approximately one third reported that they did
      not have adequate consultations with the doctors in the ward or with the MET.
      Only 13% of the nurses stated that the training was adequate (0% in medical
      wards). CONCLUSIONS: Nurses indicated a strong demand for training on NIV, in
      order to improve their involvement with the therapeutic program and for better
      communication with the MET and ward doctors. We conclude that active research
      towards understanding their point of view should be included as part of the
      quality control of NIV treatments outside the ICU.

PMID- 19153556
TI  - Human embryonic stem cells: 10 years on.
AB  - Substantial advances in the biology of human embryonic stem (ES) cells, and the
      technology for working with them, have been made over the past 10 years.
      Regulatory frameworks for their study are well developed, although some countries
      remain particularly restrictive. Markers and criteria for characterising human ES
      cells are also generally agreed, and protocols for promoting their
      differentiation are being established, providing the groundwork for the
      development of applications over the next 10 years. The recent appearance of
      technology to convert somatic cells to 'induced Pluripotent Stem Cells' closely
      resembling ES cells will certainly speed up these developments.

PMID- 19153555
TI  - Genetically engineered resistance for MMP collagenases promotes abdominal aortic
      aneurysm formation in mice infused with angiotensin II.
AB  - Clinical evidence links increased aortic collagen content and stiffness to
      abdominal aortic aneurysm (AAA) formation. However, the possibility that excess
      collagen contributes to AAA formation remains untested. We investigated the
      hypothesis that augmented collagen promotes AAA formation, and employed apoE-null
      mice expressing collagenase-resistant mutant collagen (Col(R/R)/apoE(-/-)),
      heterozygote (Col(R/+)/apoE(-/-)), or wild-type collagen (Col(+/+)/apoE(-/-))
      infused with angiotensin II to induce AAA. As expected, the aortas of
      Col(R/R)/apoE(-/-) mice contained more interstitial collagen than those from the
      other groups. Angiotensin II treatment elicited more AAA formation in
      Col(R/R)/apoE(-/-) mice than Col(R/+)/apoE(-/-) or Col(+/+)/apoE(-/-) mice.
      Aortic circumferences correlated positively with collagen content, determined by
      picrosirius red and Masson trichrome staining. Mechanical testing of aortas of
      Col(R/R)/apoE(-/-) mice showed increased stiffness and susceptibility to
      mechanical failure compared to those of Col(+/+)/apoE(-/-) mice. Optical analysis
      further indicated altered collagen fiber orientation in the adventitia of
      Col(R/R)/apoE(-/-) mice. These results demonstrate that collagen content
      regulates aortic biomechanical properties and influences AAA formation.

PMID- 19153557
TI  - Neural fractalkine expression is closely linked to pain and pancreatic neuritis
      in human chronic pancreatitis.
AB  - The chemokine fractalkine induces migration of inflammatory cells into inflamed
      tissues, thereby aggravating inflammatory tissue damage and fibrosis.
      Furthermore, fractalkine increases neuropathic pain through glial activation,
      which can be diminished by blocking of its receptor, CX3CR1, through neutralizing
      antibodies. As chronic pancreatitis (CP) is characterized by tissue infiltration
      of inflammatory cells, fibrosis, pancreatic neuritis and severe pain, the roles
      of fractalkine and CX3CR1 were investigated in CP (n=61) and normal pancreas (NP,
      n=21) by QRT-PCR, western blot and immunohistochemistry analyses. Their
      expression correlated with the severity of pancreatic neuritis, fibrosis,
      intrapancreatic nerve fiber density and hypertrophy, pain, CP duration and with
      the amount of inflammatory cell infiltrate immuno-positive for CD45 and CD68. To
      investigate the influence of fractalkine on pancreatic fibrogenesis, human
      pancreatic stellate cells (hPSCs) were isolated from patients with CP, incubated
      with fractalkine and then Collagen-1 and alpha-smooth muscle actin (alpha-SMA)
      expressions were measured. CX3CR1, but not fractalkine, mRNA was overexpressed in
      CP. In contrast, the protein levels of both CX3CR1 and fractalkine were
      upregulated. Neuro-immunoreactivity for fractalkine and CX3CR1 was strongest in
      patients suffering from severe pain and pancreatic neuritis. Long-term suffering
      from CP was noticeably related to increased neural immunoreactivity of
      fractalkine. Furthermore, fractalkine and CX3CR1 mRNA overexpressions were
      associated with enhanced lymphocyte and macrophage infiltration. Advanced
      fibrosis was associated with increased fractalkine expression, whereas in vitro
      fractalkine had no significant impact on collagen-1 and alpha-SMA expressions in
      hPSCs. Therefore, pancreatic fractalkine expression appears to be linked to
      visceral pain and to the recruitment of inflammatory cells into the pancreatic
      tissue and nerve fibers, with subsequent pancreatic neuritis. However, pancreatic
      fibrogenesis is probably indirectly influenced by fractalkine. Taken together,
      these novel findings suggest that CX3CR1 represents a potential novel therapeutic
      target to reduce inflammation and modulate pain in CP.

PMID- 19153559
TI  - Is intravenous recombinant plasminogen activator effective up to 4.5 h after
      onset of ischemic stroke?
AB  - Randomized, controlled trials and subsequent observational studies in routine
      clinical practice have shown that intravenous recombinant tissue plasminogen
      activator is safe and effective when used in selected patients within 3h of the
      onset of acute ischemic stroke. Results of the ECASS III (European Cooperative
      Acute Stroke Study III) trial have now confirmed the finding of a previous meta
      analysis of data from individual patients from smaller trials, which showed that
      the time-window for benefit actually extends to 4.5h. However, the absolute
      benefit of treatment falls substantially with time after the onset of ischemic
      stroke and clinicians should, therefore, still aim to treat patients with
      intravenous recombinant tissue plasminogen activator within 90 min of stroke
      onset, if at all possible. Ongoing trials aim to determine whether eligibility
      for thrombolysis can be extended in other ways, such as to patients aged over 80
      years, patients with severe stroke, or patients with lacunar stroke.

PMID- 19153560
TI  - Primary prevention of cardiovascular events in diabetes: is there a role for
      aspirin?
AB  - The POPADAD (Prevention Of Progression of Arterial Disease And Diabetes) study
      did not show a benefit for low-dose aspirin therapy or administration of
      antioxidants for the primary prevention of cardiovascular disease events in
      individuals with diabetes and asymptomatic peripheral arterial disease. Although
      low-dose aspirin continues to be recommended in international guidelines, no
      convincing trial-based evidence exists that supports its routine use for primary
      prevention of cardiovascular disease in people with diabetes. This paradox is
      unhelpful and the guidelines should be relaxed until definitive evidence becomes
      available.

PMID- 19153561
TI  - Does low-dose growth hormone therapy improve the body composition of patients
      infected with HIV?
AB  - Use of highly active antiretroviral therapy in patients infected with HIV can
      lead to lipodystrophy, a condition characterized by changes in body-fat
      distribution. In addition, infected individuals often exhibit relative growth
      hormone (GH) deficiency. Treatment with supraphysiological levels of GH improves
      body composition in these patients, but is associated with adverse effects. In
      this Practice Point commentary, we discuss an 18-month, randomized, double-blind,
      placebo-controlled study of low-dose GH therapy in 56 HIV-positive adults with
      lipodystrophy and relative GH deficiency. Lo et al. found that administration of
      low-dose GH (mean 0.33 mg daily) led to improvements in body composition (e.g.
      visceral adipose-tissue area), diastolic blood pressure and triglyceride levels.
      Furthermore, this treatment regimen was not associated with an increased
      incidence of adverse events compared with placebo. Here, we discuss the
      implications of the findings of Lo et al., and describe additional strategies
      that might be used to treat lipodystrophy in HIV-positive individuals.

PMID- 19153558
TI  - Chloride channels as drug targets.
AB  - Chloride channels represent a relatively under-explored target class for drug
      discovery as elucidation of their identity and physiological roles has lagged
      behind that of many other drug targets. Chloride channels are involved in a wide
      range of biological functions, including epithelial fluid secretion, cell-volume
      regulation, neuroexcitation, smooth-muscle contraction and acidification of
      intracellular organelles. Mutations in several chloride channels cause human
      diseases, including cystic fibrosis, macular degeneration, myotonia, kidney
      stones, renal salt wasting and hyperekplexia. Chloride-channel modulators have
      potential applications in the treatment of some of these disorders, as well as in
      secretory diarrhoeas, polycystic kidney disease, osteoporosis and hypertension.
      Modulators of GABA(A) (gamma-aminobutyric acid A) receptor chloride channels are
      in clinical use and several small-molecule chloride-channel modulators are in
      preclinical development and clinical trials. Here, we discuss the broad
      opportunities that remain in chloride-channel-based drug discovery.

PMID- 19153562
TI  - Does tibolone reduce the risk of fracture in older postmenopausal women with
      osteoporosis?
AB  - This Practice Point commentary discusses a double-blind, placebo-controlled trial
      by Cummings et al. that investigated the effects of tibolone 1.25 mg per day in
      4,534 postmenopausal women (mean age 68 years) with osteoporosis. Tibolone is a
      synthetic steroid with estrogenic, progestational and androgenic effects. It has
      been used as an alternative to estrogen to treat menopausal symptoms for 30
      years. Cummings et al. found that tibolone reduced the incidence of vertebral
      fractures by 45%, nonvertebral fractures by 26%, breast cancer by 68% and colon
      cancer by 69%. The trial was discontinued 2 months before a median treatment time
      of 3 years because the major end point (reduction of fractures) was reached. In
      addition, tibolone increased the risk of stroke, although the absolute risk was
      small. Similarly to other compounds with estrogenic activity that increase the
      risk of stroke, such as estrogen and selective estrogen-receptor modulators,
      clinicians must weigh the risks and benefits of therapy for individual patients.
      This risk might be lower in women aged 50-60 years than in those aged >60 years.

PMID- 19153564
TI  - Evolution of nonsurgical therapy for colorectal cancer.
AB  - The management of colorectal cancer (CRC) has changed considerably in the past 15
      years with the introduction of multiple novel active therapeutic agents.
      Chemotherapy regimens combining a fluoropyrimidine with either oxaliplatin or
      irinotecan are standard first-line and second-line therapy for advanced and
      metastatic disease. The first-line use of these combinations produces tumor
      response rates of approximately 50% and a median overall survival of
      approximately 20 months. Addition of bevacizumab to first-line treatment and
      addition of cetuximab to salvage therapy for patients who fail to respond to
      irinotecan have contributed to further increases in tumor response rates and
      enhanced progression-free survival. Such approaches have produced only marginal
      overall survival benefits, however, and entail considerable cost. Adjuvant
      chemotherapy, delivered after surgical resection of the primary tumor, increases
      cure rates by approximately 10% for stage III disease and approximately 3-4% for
      stage II disease. Encouraging reductions in local relapse rates have been
      observed in patients with early rectal cancer who have undergone
      chemoradiotherapy, and increasingly complex regimens are currently being explored
      in phase II clinical trials in an attempt to increase both the operability and
      long-term local control of CRC. The greater the therapeutic choice, the greater
      the cost (both financial and in terms of toxicity), thus the keener the clinical
      community becomes to develop biomarkers to select patient populations who will be
      most likely to benefit from a specific agent.

PMID- 19153565
TI  - How to critically appraise an article.
AB  - Critical appraisal is a systematic process used to identify the strengths and
      weaknesses of a research article in order to assess the usefulness and validity
      of research findings. The most important components of a critical appraisal are
      an evaluation of the appropriateness of the study design for the research
      question and a careful assessment of the key methodological features of this
      design. Other factors that also should be considered include the suitability of
      the statistical methods used and their subsequent interpretation, potential
      conflicts of interest and the relevance of the research to one's own practice.
      This Review presents a 10-step guide to critical appraisal that aims to assist
      clinicians to identify the most relevant high-quality studies available to guide
      their clinical practice.

PMID- 19153566
TI  - Reassuring results with regard to the effect of donor nephrectomy on
      cardiovascular outcomes.
AB  - This article discusses the conclusions of a retrospective cohort study reported
      by Garg et al. on behalf of the Donor Nephrectomy Outcomes Research (DONOR)
      Network. This study compared the incidence of cardiovascular events in a cohort
      of kidney donors with that in a matched control population, to establish whether
      living kidney donation is associated with increased cardiovascular risk. Garg et
      al. found that living kidney donors had a very low risk of death or
      cardiovascular events that was not significantly different to that of the control
      population (2.0 vs 2.7 events per 1,000 person-years; hazard ratio 0.7, 95% CI
      0.4-1.2). During follow-up, hypertension was diagnosed more frequently among
      donors than controls, but this finding might reflect the close monitoring of
      donors. Although the study provides reassuring information for counseling
      potential kidney donors, the sample of patients was not sufficiently large to
      resolve uncertainties over the influence of reduced kidney function on the risk
      of cardiovascular disease.

PMID- 19153563
TI  - Diagnosis and management of fistulizing Crohn's disease.
AB  - The transmural inflammation characteristic of Crohn's disease predisposes
      patients to the formation of fistulas. Up to 50% of patients with Crohn's disease
      are affected by fistulas, which is a major problem given the considerable
      morbidity associated with this complication. Appropriate treatment of fistulas
      requires knowledge of specific pharmacological and surgical therapies. Treatment
      options depend on the severity of symptoms, fistula location, the number and
      complexity of fistula tracts, and the presence of rectal complications. Internal
      fistulas, such as ileoileal or ileocecal fistulas, are mostly asymptomatic and do
      not require intervention. By contrast, perianal fistulas can be painful and
      abscesses may develop that require surgical drainage with or without seton
      placement, transient ileostomy, or in severe cases, proctectomy. This Review
      describes the epidemiology and pathology of fistulizing Crohn's disease.
      Particular focus is given to external and perianal fistulas, for which treatment
      options are well established. Available therapeutic options, including novel
      therapies, are discussed. Wherever possible, practical and evidence-based
      treatment regimens for Crohn's disease-associated fistulas are provided.

PMID- 19153567
TI  - Optimal timing of surgery after preoperative chemoradiotherapy for rectal cancer.
AB  - The timing of surgery in rectal cancer treatment after neoadjuvant
      chemoradiotherapy is debated, mainly because of downsizing and repopulation of
      tumor cells. The retrospective analysis of prospectively collected data from a
      series of patients with locally advanced rectal cancer by Lim et al. has tried to
      evaluate whether timing of surgery after neoadjuvant chemoradiotherapy has any
      effect on tumor regression, sphincter preservation, local recurrence rate or
      overall survival. The study included 397 patients who had received
      chemoradiotherapy and surgery with different time intervals between the use of
      these modalities. No differences regarding all four parameters were found in
      patients with a time interval less or greater than 41 days. Some methodological
      reasons can be discussed, but the only way to answer the question of timing is,
      of course, to do a randomized trial.

PMID- 19153568
TI  - Should irinotecan or etoposide be used in combination with carboplatin for small
      cell lung cancer?
AB  - Little progress has been made in the treatment of small cell lung cancer over the
      past two decades. Superiority of combined irinotecan-cisplatin over standard
      etoposide-cisplatin in a Japanese phase III trial was not confirmed in two
      subsequent US studies. In this Practice Point we discuss a randomized, phase III
      trial by Hermes and colleagues, which included 220 patients with extensive
      disease small cell lung cancer and showed superiority of carboplatin-irinotecan
      versus carboplatin-oral etoposide. In this trial, 47% of patients had a
      performance status > or = 3 and 35% were older than 70 years, which represents a
      typical clinical practice population of patients; however, oral administration of
      etoposide and an arbitrary dose reduction in elderly and unfit patients represent
      limitations of the study. A European trial of irinotecan-carboplatin versus
      intravenous etoposide-carboplatin has completed accrual and results will be
      analyzed in 2009. Although the results of the study by Hermes et al. are of
      interest, substitution of etoposide by irinotecan can not be recommended.

PMID- 19153569
TI  - Fludarabine, cyclophosphamide and rituximab for chronic lymphocytic leukemia: no
      country for old men?
AB  - The combination of fludarabine, cyclophosphamide and rituximab is regarded as the
      gold-standard treatment for chronic lymphocytic leukemia in many parts of the
      world, although rituximab has not yet been licensed for this use. To date, no
      randomized, controlled trials have been fully published that demonstrate the
      superiority of this regimen over other treatments. The results of an open-label,
      phase II trial with long-term follow-up data on 300 patients with chronic
      lymphocytic leukemia treated with this regimen are discussed here. Although this
      study reported impressive efficacy, information on modern prognostic markers such
      as immunoglobulin gene mutational status and chromosomal deletions was absent,
      and so it is impossible to say whether the most challenging cases, as identified
      by these markers, were included in the trial. The most important toxicity was
      prolonged cytopenia, which occurred both at the end of treatment and later after
      bone-marrow recovery. At least half of patients with chronic lymphocytic leukemia
      are over 70 years of age and this regimen might be too toxic for such
      individuals.

PMID- 19153570
TI  - Does statin use affect the risk of developing prostate cancer?
AB  - This commentary discusses the findings of Agalliu and colleagues, who performed a
      population-based, case-control study on the association between statin drugs and
      prostate cancer risk. Consistent with recent studies, statins were not associated
      with overall prostate cancer risk, but users had a possible lower risk of
      advanced disease. Obese men taking a statin had a higher risk of prostate cancer
      than those not taking a statin; however, a previously conducted, large,
      prospective, cohort study did not observe this association. This unexpected
      finding by Agalliu et al. could be a chance result, or could have arisen because
      of complex bias. Although statins might favorably affect men's prostate health,
      evidence is too limited to recommend statin use for the prevention of advanced
      prostate cancer. Consideration of the harms and benefits when prescribing a
      statin for vascular indications, including in obese men, should not presently
      include prostate cancer risk.

PMID- 19153571
TI  - Epidural steroid injections in the management of a patient with spinal stenosis
      and urinary urgency.
AB  - BACKGROUND: A 79-year-old woman with a history of chronic back pain and urinary
      urgency presented to a spine center for treatment and evaluation for axial low
      back pain. The patient described the back pain as severe with intermittent
      radiation into the right leg; her pain intensity was 7 out of 10 on a visual
      analog scale. She described her sense of urgency as severe, and could delay
      urination for 10 min or less. She described her bladder control as 6 out of 10 on
      the urgency perception score (with 0 being perfect control). INVESTIGATIONS:
      Physical examination, including manual muscle testing, test for sensation to fine
      touch, reflex assessment and assessment of gait pattern, and MRI of the lumbar
      spine. DIAGNOSIS: Overactive bladder associated with severe central-canal
      stenosis at L4-5, in the setting of anterolisthesis. MANAGEMENT: Fluoroscopically
      guided caudal epidural steroid injection; 60 mg of triamcinolone, 3 ml of 1%
      lidocaine hydrochloride and 3 ml of normal saline, injected in increments.

PMID- 19153572
TI  - Is neonatal circumcision clinically beneficial? Argument against.

PMID- 19153573
TI  - Is the tension-free vaginal tape procedure for stress urinary incontinence safe
      and effective in the long term?
AB  - This Practice Point discusses the study by Nilsson and colleagues, who reported
      the first 10-year follow-up outcome analysis of patients who underwent a tension
      free vaginal tape procedure for stress urinary incontinence. The study, however,
      leaves some issues open to question. Long duration of follow-up is a strength of
      the study, but also presents problems associated with patients' recall.
      Subjective outcome assessment might change as a patient ages, and clinical
      evidence suggests that differences in subjective outcomes exist between short
      term and longer-term follow-up. In addition, Nilsson et al. did not report
      functional complications or healing abnormalities. De novo storage symptoms are
      not negligible after tension-free vaginal tape procedures; nor are healing
      abnormalities (e.g. mesh erosion). Clear guidelines need to be developed for the
      long-term outcome assessment of urinary incontinence and its treatments, and
      subjective outcomes must be adequately incorporated into evaluation.

PMID- 19153574
TI  - Interactions between BDNF Val66Met polymorphism and early life stress predict
      brain and arousal pathways to syndromal depression and anxiety.
AB  - Individual risk markers for depression and anxiety disorders have been identified
      but the explicit pathways that link genes and environment to these markers remain
      unknown. Here we examined the explicit interactions between the brain-derived
      neurotrophic factor (BDNF) Val66Met gene and early life stress (ELS) exposure in
      brain (amygdala-hippocampal-prefrontal gray matter volume), body (heart rate),
      temperament and cognition in 374 healthy European volunteers assessed for
      depression and anxiety symptoms. Brain imaging data were based on a subset of 89
      participants. Multiple regression analysis revealed main effects of ELS for body
      arousal (resting heart rate, P=0.005) and symptoms (depression and anxiety,
      P<0.001) in the absence of main effects for BDNF. In addition, significant BDNF
      ELS interactions indicated that BDNF Met carriers exposed to greater ELS have
      smaller hippocampal and amygdala volumes (P=0.013), heart rate elevations
      (P=0.0002) and a decline in working memory (P=0.022). Structural equation path
      modeling was used to determine if this interaction predicts anxiety and
      depression by mediating effects on the brain, body and cognitive measures. The
      combination of Met carrier status and exposure to ELS predicted reduced gray
      matter in hippocampus (P<0.001), and associated lateral prefrontal cortex
      (P<0.001) and, in turn, higher depression (P=0.005). Higher depression was
      associated with poorer working memory (P=0.005), and slowed response speed. The
      BDNF Met-ELS interaction also predicted elevated neuroticism and higher
      depression and anxiety by elevations in body arousal (P<0.001). In contrast, the
      combination of BDNF V/V genotype and ELS predicted increases in gray matter of
      the amygdala (P=0.003) and associated medial prefrontal cortex (P<0.001), which
      in turn predicted startle-elicited heart rate variability (P=0.026) and higher
      anxiety (P=0.026). Higher anxiety was linked to verbal memory, and to
      impulsivity. These effects were specific to the BDNF gene and were not evident
      for the related 5HTT-LPR polymorphism. Overall, these findings are consistent
      with the correlation of depression and anxiety, yet suggest that partially
      differentiated gene-brain cognition pathways to these syndromes can be
      identified, even in a nonclinical sample. Such findings may aid establishing an
      evidence base for more tailored intervention strategies.

PMID- 19153575
TI  - Organization and dynamics of PDZ-domain-related supramodules in the postsynaptic
      density.
AB  - As the major components of the postsynaptic density of excitatory neuronal
      synapses, PDZ-domain-containing scaffold proteins regulate the clustering of
      surface glutamate receptors, organize synaptic signalling complexes, participate
      in the dynamic trafficking of receptors and ion channels, and coordinate
      cytoskeletal dynamics. These scaffold proteins often contain multiple PDZ
      domains, with or without other protein-binding modules, and they usually lack
      intrinsic enzymatic activities. Recent biochemical and structural studies have
      shown that tandemly arranged PDZ domains often serve as structural and functional
      supramodules that could regulate the organization and dynamics of synaptic
      protein complexes, thus contributing to the broad range of neuronal activity.

PMID- 19153577
TI  - Conflict-induced behavioural adjustment: a clue to the executive functions of the
      prefrontal cortex.
AB  - The behavioural adjustment that follows the experience of conflict has been
      extensively studied in humans, leading to influential models of executive-control
      adjustment. Recent studies have revealed striking similarities in conflict
      induced behavioural adjustment between humans and monkeys, indicating that
      monkeys can provide a model to study the underlying neural substrates and
      mechanisms of such behaviour. These studies have advanced our knowledge about the
      role of different prefrontal brain regions, including the anterior cingulate
      cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC), in executive-control
      adjustment and suggest a pivotal role for the DLPFC in the dynamic tuning of
      executive control and, consequently, in behavioural adaptation to changing
      environments.

PMID- 19153578
TI  - Identity crisis for adult periventricular neural stem cells: subventricular zone
      astrocytes, ependymal cells or both?
AB  - A population of neural stem cells (NSCs) resides adjacent to the lateral
      ventricles in the adult mammalian brain. Despite knowledge of their existence
      since the early 1990s, their identity remains controversial, with evidence
      suggesting that they may be ependymal cells, glial fibrillary acidic protein
      (GFAP)-expressing subventricular zone (SVZ) cells or several distinct NSC
      populations. This issue has major implications for the therapeutic use of NSCs as
      well as for the study and treatment of brain cancers. Recent studies have both
      shed light on the issue and added to the controversy.

PMID- 19153576
TI  - The molecular and cellular biology of enhanced cognition.
AB  - Most molecular and cellular studies of cognitive function have focused on either
      normal or pathological states, but recent research with transgenic mice has
      started to address the mechanisms of enhanced cognition. These results point to
      key synaptic and nuclear signalling events that can be manipulated to facilitate
      the induction or increase the stability of synaptic plasticity, and therefore
      enhance the acquisition or retention of information. Here, we review these
      surprising findings and explore their implications to both mechanisms of learning
      and memory and to ongoing efforts to develop treatments for cognitive disorders.
      These findings represent the beginning of a fundamental new approach in the study
      of enhanced cognition.

PMID- 19153579
TI  - Hydration increases cell metabolism.

PMID- 19153580
TI  - The effect of a low-fat, high-protein or high-carbohydrate ad libitum diet on
      weight loss maintenance and metabolic risk factors.
AB  - BACKGROUND: High-protein (HP) diets are often advocated for weight reduction and
      weight loss maintenance. OBJECTIVE: The aim was to compare the effect of low-fat,
      high-carbohydrate (HC) and low-fat, HP ad libitum diets on weight maintenance
      after weight loss induced by a very low-calorie diet, and on metabolic and
      cardiovascular risk factors in healthy obese subjects. DESIGN: Forty-eight
      subjects completed the study that consisted of an energy restriction period of 5
      6 weeks followed by a weight maintenance period of 12 weeks. During weight
      maintenance subjects received maltodextrin (HC group) or protein (HP group)
      (casein (HPC subgroup) or whey (HPW subgroup)) supplements (2 x 25 g per day),
      respectively and consumed a low-fat diet. RESULTS: Subjects in the HP diet group
      showed significantly better weight maintenance after weight loss (2.3 kg
      difference, P=0.04) and fat mass reduction (2.2 kg difference, P=0.02) than
      subjects in the HC group. Triglyceride (0.6 mM difference, P=0.01) and glucagon
      (9.6 pg ml(-1) difference, P=0.02) concentrations increased more in the HC diet
      group, while glucose (0.3 mM difference, P=0.02) concentration increased more in
      the HP diet group. Changes in total cholesterol, low-density lipoprotein
      cholesterol, high-density lipoprotein-cholesterol, insulin, HOMAir index, HbA1c,
      leptin and adiponectin concentrations did not differ between the diets. No
      differences were found between the casein- or whey-supplemented HP groups.
      CONCLUSIONS: These results show that low-fat, high-casein or whey protein weight
      maintenance diets are more effective for weight control than low-fat, HC diets
      and do not adversely affect metabolic and cardiovascular risk factors in weight
      reduced moderately obese subjects without metabolic or cardiovascular
      complications.

PMID- 19153581
TI  - Common genetic variation near MC4R is associated with eating behaviour patterns
      in European populations.
AB  - Both rs17782313 (near MC4R) and rs1421085 (FTO) polymorphisms have been
      consistently associated with increased risk of obesity and with body mass index
      (BMI) variation. An effect of both polymorphisms on satiety has recently been
      suggested. We genotyped rs17782313 and rs1421085 in 5764 relatives from 1109
      French pedigrees with familial obesity, 1274 Swiss class III obese adults as well
      as in 4877 French adults and 5612 Finnish teenagers from two randomly selected
      population cohorts. In all subjects, eating behaviour traits were documented
      through questionnaires. We first assessed the association of both single
      nucleotide polymorphisms with BMI and then studied eating behaviour. Under an
      additive model, the rs17782313-C MC4R allele showed a trend towards higher
      percentages of snacking in both French obese children (P=0.01) and Swiss obese
      adults (P=0.04) as well as in adolescents from the Finnish general population
      (P=0.04). In French adults with familial obesity, this allele tended to be also
      associated with a higher Stunkard hunger score (P=0.02) and in obese children
      with a higher prevalence of eating large amounts of food (P=0.04). However, no
      consistent association of the FTO rs1421085-C allele and available eating
      behaviour trait was found in our studied populations. The rs17782313-C allele
      nearby MC4R may modulate eating behaviour-related phenotypes in European obese
      and randomly selected populations, in both children and adults, supporting a
      regulatory role of this genetic variant on eating behaviour, as previously shown
      for MC4R non-synonymous loss-of-function mutations. The potential effect of the
      obesity-associated FTO gene on eating behaviour deserves additional
      investigation.

PMID- 19153582
TI  - Effect of a lifestyle intervention on change in cardiorespiratory fitness in
      adults with type 2 diabetes: results from the Look AHEAD Study.
AB  - OBJECTIVE: To examine the effect of an intensive lifestyle weight loss
      intervention (ILI) compared to diabetes support and education (DSE) on changes in
      fitness and physical activity in the Look AHEAD trial. DESIGN: Randomized
      clinical trial to compare a lifestyle intervention for weight loss with a DSE
      condition in individuals with type 2 diabetes. SUBJECTS: Data from 4376
      overweight or obese adults with type 2 diabetes (age=58.7+/-6.8 years, body mass
      index (BMI)=35.8+/-5.8 kg/m(2)) who completed 1 year of the Look AHEAD trial and
      had available fitness data were analyzed. INTERVENTION: Subjects were randomly
      assigned to DSE or ILI. DSE received standard care plus three education sessions
      over the 1-year period. ILI included individual and group contact throughout the
      year, restriction in energy intake and 175 min per week of prescribed physical
      activity. MEASUREMENTS: Fitness was assessed using a submaximal graded exercise
      test. Physical activity was assessed by questionnaire in a subset of 2221
      subjects. RESULTS: Change in fitness was statistically greater in ILI vs DSE
      after adjustment for baseline fitness (20.9 vs 5.7%; P<0.0001). Multivariate
      analysis showed that change in fitness was greater in overweight vs obese Class
      II and III (P<0.05). Physical activity increased by 892+/-1694 kcal per week in
      ILI vs 108+/-1254 kcal per week in DSE (P<0.01). Changes in fitness (r=0.41) and
      physical activity (r=0.42) were significantly correlated with weight loss
      (P<0.0001). CONCLUSIONS: The ILI was effective in increasing physical activity
      and improving cardiorespiratory fitness in overweight and obese individuals with
      type 2 diabetes. This effect may add to weight loss in improving metabolic
      control in patients in lifestyle intervention programs.

PMID- 19153583
TI  - Multivitamin supplementation of Wistar rats during pregnancy accelerates the
      development of obesity in offspring fed an obesogenic diet.
AB  - OBJECTIVE: The effect of gestational multivitamin supplementation on the
      development of obesity in rat offspring fed an obesogenic diet was investigated.
      DESIGN: Pregnant Wistar rats (n=10 per group) were fed the AIN-93G diet with the
      recommended vitamin (RV) content or a 10-fold increase (high vitamin, HV). At
      weaning, 10 males and 10 females, from separate dams, and from each gestational
      diet group were weaned to the liquid obesogenic diet for 48 weeks post-weaning.
      MEASUREMENTS: Body weight (BW) was measured weekly, and food intake over 24 h was
      measured once every 3 weeks for 24 weeks. Every 4 weeks, after an overnight fast,
      food intake over 1 h was measured 30 min after a gavage of water or glucose. An
      oral glucose tolerance test (OGTT) was carried out every 3-5 weeks. Post-weaning
      fasting glucose, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), and systolic
      blood pressure (SBP) were measured. RESULTS: No difference in BW at birth or
      litter size was observed. Males and females from HV dams gained 17% (P<0.05) and
      37% (P<0.001) more BW at 48 weeks post-weaning, and consumed 18% (P=0.07) and 20%
      (P<0.05) more food. One-hour food intake after water and glucose preloads was 27%
      (P<0.01) and 34% (P<0.05) higher in males from HV dams. Fasting ghrelin and GLP-1
      were 27 and 32% higher in males from HV dams at weaning (P<0.05). Blood glucose
      response to the OGTT was greater in both males and females from HV dams at 13
      weeks post-weaning (P<0.05), and the insulin resistance index was 76 and 43%
      higher in females from HV dams at 14 and 28 weeks post-weaning (P<0.05). SBP was
      23 and 16% higher at 44 weeks post-weaning in male and females (P<0.01).
      CONCLUSION: High multivitamin intake during pregnancy increases the phenotypic
      expression of obesity and components of the metabolic syndrome in both female and
      male rats fed an obesogenic diet.

PMID- 19153586
TI  - Whole-body vibration and weight loss: truth or consequence?

PMID- 19153585
TI  - Impact of overweight and obesity on hospitalization: race and gender differences.
AB  - OBJECTIVE: To examine associations between weight status and number of all-cause
      and cause-specific hospitalizations overall, and by race and gender. DESIGN:
      Longitudinal cohort study. SUBJECTS: White and black adults (n=15 355) from the
      Atherosclerosis Risk in Communities Study who were normal weight (body mass
      index: >or=18.5 to <25.0 kg m(-2); n=4997), overweight (>or=25.0 to <30.0 kg m(
      2); n=6100), or obese (>or=30.0 kg m(-2); n=4258) at baseline. MEASUREMENTS:
      Information on hospitalizations was collected using community and cohort
      surveillance methods. Negative binomial models adjusted for race, gender, field
      center, age, physical activity, education level, smoking status, alcoholic
      beverage consumption and health insurance at baseline. Adjusted numbers of
      hospitalizations were calculated after setting covariates to the mean value (for
      continuous variables) or to the average distribution (for categorical variables)
      observed in the entire cohort and are expressed as the number of hospitalizations
      per 1000 adults followed over a period of 13 years. RESULTS: The covariate
      adjusted average number of all-cause hospitalizations was 1316 per 1000 normal
      weight, 1543 per 1000 overweight and 2025 per 1000 obese. Normal weight women had
      significantly fewer hospitalizations than normal weight men (1173 versus 1515 per
      1000), but the increase associated with being obese on the number of all-cause
      hospitalizations was larger in women than men (791 versus 589 per 1000). There
      was no significant difference detected between the number of hospitalizations in
      normal weight whites and blacks, and the increase in hospitalizations with
      overweight or obesity was also not different. Effects of weight status on several
      primary causes of hospitalization differed by gender and race group. CONCLUSION:
      Our work suggests that obesity prevention may reduce hospitalizations, a major
      component of rising healthcare costs. The impact of successful obesity prevention
      is likely to be larger in women than in men, and similar in blacks and whites.

PMID- 19153588
TI  - Physician utilization among adults with traumatic spinal cord injury in Ontario:
      a population-based study.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To describe the physician
      utilization patterns (family physicians (FP), specialist and emergency department
      (ED) visits) of adults with traumatic spinal cord injury (SCI) 1 year after the
      initial injury. SETTING: Ontario, Canada. METHODS: A total of 559 individuals
      with a traumatic SCI were identified. Five administrative databases were linked
      to examine health-care utilization in acute care, inpatient rehabilitation,
      chronic care rehabilitation, outpatient physician visits and ED visits. Factors
      predicting frequent physician, specialist and ED use were identified. RESULTS:
      The mean number of physician visits for traumatic SCI patients during the first
      year after their injury onset was 31.7 (median 26). FPs had the greatest number
      of visits (mean 11.6, median 7) followed by physiatrists (mean 6.1, median 2).
      Factors predicting 50 or more physician visits included age 70 or above (OR=3.6,
      95% CI=2.0-6.5), direct discharge to chronic care (OR=3.6, 95% CI=1.0-13.1) and
      in-hospital complication (OR=2.34, 95% CI=1.3-4.3). Age 70 or less (OR=0.19, 95%
      CI=0.0-0.9) and direct discharge to chronic care were associated with 50 or more
      specialist visits. Only rurality predicted two or more visits to the ED.
      CONCLUSIONS: Individuals with traumatic SCI show significant physician
      utilization, especially among their FPs and physiatrists. Although the factors
      predicting higher physician and specialist utilization may reflect individuals
      with the most severe impairment, comorbid conditions or lack of social support,
      the model for higher ED visits may point to limited accessibility to/availability
      of primary care services for SCI patients in rural regions.

PMID- 19153589
TI  - Relationship between median nerve somatosensory evoked potentials and spinal cord
      injury levels in patients with quadriplegia.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To observe if there is a
      relationship between the level of injury by the American Spinal Cord Injury
      Association (ASIA) and cortical somatosensory evoked potential (SSEP) recordings
      of the median nerve in patients with quadriplegia. SETTING: Rehabilitation
      Outpatient Clinic at the university hospital in Brazil. METHODS: Fourteen
      individuals with quadriplegia and 8 healthy individuals were evaluated.
      Electrophysiological assessment of the median nerve was performed by evoked
      potential equipment. The injury level was obtained by ASIA. N(9), N(13) and N(20)
      were analyzed based on the presence or absence of responses. The parameters used
      for analyzing these responses were the latency and the amplitude. Data were
      analyzed using mixed-effect models. RESULTS: N(9) responses were found in all
      patients with quadriplegia with a similar latency and amplitude observed in
      healthy individuals; N(13) responses were not found in any patients with
      quadriplegia. N(20) responses were not found in C5 patients with quadriplegia but
      it was present in C6 and C7 patients. Their latencies were similar to healthy
      individuals (P>0.05) but the amplitudes were decreased (P<0.05). CONCLUSION: This
      study suggests that the SSEP responses depend on the injury level, considering
      that the individuals with C6 and C7 injury levels, both complete and incomplete,
      presented SSEP recordings in the cortical area. It also showed a relationship
      between the level of spinal cord injury assessed by ASIA and the median nerve
      SSEP responses, through the latency and amplitude recordings.

PMID- 19153590
TI  - Dual-energy X-ray absorptiometry overestimates bone mineral density of the lumbar
      spine in persons with spinal cord injury.
AB  - BACKGROUND: Bone mineral density (BMD) of the lumbar spine (L-spine) has been
      reported to be normal or increased in persons with chronic spinal cord injury
      (SCI). OBJECTIVE: To determine BMD of the L-spine by dual-energy X-ray
      absorptiometry (DXA) and quantitative computerized tomography (qCT) in men with
      chronic SCI compared with able-bodied controls. DESIGN: Cross-sectional,
      comparative study. SETTING: Clinical research unit, Veterans Affairs Medical
      Center, Bronx, NY, USA and Kessler Institute of Rehabilitation, West Orange, NJ,
      USA. METHODS: Measurements of the L-spine were made in 20 men with SCI and
      compared with 15 able-bodied controls. The DXA images were acquired on a GE Lunar
      DPX-IQ. The qCT images of the L-spine were acquired on a Picker Q series
      computerized tomographic scanner. RESULTS: The mean ages for the SCI and control
      groups were 44+/-13 vs 42+/-9 years, and the duration of injury of the group with
      SCI was 14+/-11 years. There were no significant differences between the SCI and
      control groups for L-spine DXA BMD (1.391+/-0.210 vs 1.315+/-0.178 g/m(2)) or for
      L-spine DXA T-score (1.471+/-1.794 vs 0.782+/-1.481). L-spine qCT BMD was
      significantly lower in the SCI compared with the control group (1.296+/-0.416 vs
      1.572+/-0.382 g/m(2), P=0.05); the T-score approached significance (-1.838+/
      1.366 vs -0.963+/-1.227, P=0.059). Subjects with moderate degenerative joint
      disease (DJD) had significantly higher T-scores by DXA than those without or with
      mild DJD. CONCLUSION: Individuals with SCI who have moderate to severe DJD may
      have bone loss of the L-spine that may be underestimated by DXA, reducing
      awareness of the risk of fracture.

PMID- 19153591
TI  - Biomarkers in spinal cord injury.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: In traumatic spinal cord injury
      (SCI), much effort has been put into the evaluation of SCI severity and the
      prediction of recovery potential. An accurate prediction of the initial damage of
      the spinal cord that differentiates between the severities of SCI however, may
      help physicians in choosing a particular neuroprotective treatment in the acute
      phase. Neurochemical biomarkers may possibly fulfil these requirements. The aim
      of this review was to describe (1) the current status of neurochemical biomarkers
      in SCI; (2) their potential diagnostic role in SCI. METHODS: MEDLINE was searched
      from 1966 to 2008 to identify publications concerning biomarkers in traumatic
      SCI. RESULTS: The biomarkers S-100beta, neuron-specific enolase, neurofilament
      light chain, and Glial fibrillary acidic protein are significantly increased in
      cases of (experimental) spinal cord injury. Furthermore, increased serum
      concentrations of S-100beta have been correlated with an unfavourable functional
      outcome. Although biomarkers in SCI show promising results, considerations and
      shortcomings, such as polytrauma, haemolysis, extracerebral sources, and poor
      resuscitation, must be studied in greater detail before biomarkers can be
      utilised in the clinical care of SCI. CONCLUSIONS: Quantitative standards for
      determining the extent of SCI during the acute phase must be developed and
      validated. Even though increased concentrations of neurochemical biomarkers have
      been identified in patients with SCI, these do not yet provide a sensitive
      prognostic tool. Considering the limited availability of sensitive prognostic
      tools, neurochemical biomarkers of SCI should be evaluated and validated in
      future clinical trials.

PMID- 19153592
TI  - Complement activation and coagulation in xenotransplantation.
AB  - Xenotransplantation using porcine donors holds tremendous promise for alleviating
      the chronic shortage of human organ donors. However, transplantation from pigs
      into higher primates triggers a vigorous immune response involving complement
      activation and thrombosis. Hyperacute rejection can be prevented by using donors
      in which GalT, the gene responsible for the predominant target of anti-pig
      natural antibodies, has been deleted. Unfortunately, the adaptive response to
      GalT knockout (KO) organs has been difficult to immunosuppress. The focus has
      shifted to identifying additional genetic modifications that will extend
      xenograft survival beyond the several months currently achievable. Which gene(s)
      should be added to the GalT KO background is open to debate. Overexpression of a
      complement regulatory factor(s) seems a logical first choice, supported by recent
      in vitro data but not yet validated in preclinical models. The next obvious
      candidate would be an anticoagulant protein(s) to deal with the dysregulated
      coagulation that is almost invariably associated with xenograft rejection.
      Several potentially useful molecules have been identified, although this study is
      yet to be translated to the pig. Our understanding of the mechanisms of GalT KO
      xenograft rejection continues to grow, providing a rational basis for tailoring
      further genetic modification of the donor and immunosuppression of the recipient.

PMID- 19153593
TI  - Human respiratory syncytial virus infects and induces activation markers in mouse
      B lymphocytes.
AB  - Human respiratory syncytial virus (HRSV) is the most common cause of severe
      respiratory infections in infants and young children, often leading to
      hospitalization. Although human airway epithelial cells are the main target of
      HRSV, it has been reported that this virus can also infect professional antigen
      presenting cells such as macrophages and dendritic cells, promoting upregulation
      of maturation markers. Here, we report that mouse spleen B220(+) B lymphocytes
      were susceptible to HRSV infection in vitro, probably involving a
      glycosaminoglycan-dependent mechanism. In contrast, neither CD4(+) nor CD8(+) T
      lymphocytes were infected. In B lymphocytes, HRSV infection upregulated major
      histocompatibility complex (MHC) class II but not MHC class I molecules and
      induced the expression of the activation marker CD86.

PMID- 19153594
TI  - Isolation and characterization of liver epithelial progenitor cells from normal
      adult rhesus monkeys (Macaca mulatta).

PMID- 19153595
TI  - The TAK1-JNK cascade is required for IRF3 function in the innate immune response.
AB  - Interferon regulatory factor (IRF)3 is critical for the transcriptional induction
      of chemokines and cytokines during viral or bacterial invasion. The kinases Tank
      binding kinase (TBK)1 and Ikappa B kinase (IKK)epsilon can phosphorylate the C
      terminal part of IRF3 and play important roles in IRF3 activation. In this study,
      we show that another kinase, c-Jun-NH(2)-terminal kinase (JNK), phosphorylates
      IRF3 on its N-terminal serine 173 residue, and TAK1 can stimulate IRF3
      phosphorylation via JNK. JNK specific inhibitor SP600125 inhibits the N-terminal
      phosphorylation without affecting the C-terminal phosphorylation. In addition,
      IRF3-mediated gene expressions on lipopolysaccharide (LPS) or polyinosinic
      cytidylic acid (polyI:C) treatment are severely impaired by SP600125, as well as
      for reporter gene assay of IRF3 activation. Knockdown of TAK1 further confirmed
      these observations. Interestingly, constitutive active IRF3(5D) can be inhibited
      by SP600125; JNK1 can synergize the action of IRF3(5D), but not the S173A
      IRF3(5D) mutant. More importantly, polyI:C failed to induce the phosphorylation
      of mutant S173A and SP600125 dramatically abrogated IRF3 phosphorylation and
      dimerization that was stimulated by polyI:C. Thus, this study demonstrates that
      the TAK1-JNK cascade is required for IRF3 function, in addition to
      TBK1/IKKvarepsilon, uncovering a new mechanism for mitogen-activated protein
      (MAP) kinase to regulate the innate immunity.

PMID- 19153596
TI  - Visualization and orchestration of the dynamic molecular society in cells.

PMID- 19153597
TI  - DOG 1.0: illustrator of protein domain structures.

PMID- 19153598
TI  - TGF-beta-induced epithelial to mesenchymal transition.
AB  - During development and in the context of different morphogenetic events,
      epithelial cells undergo a process called epithelial to mesenchymal transition or
      transdifferentiation (EMT). In this process, the cells lose their epithelial
      characteristics, including their polarity and specialized cell-cell contacts, and
      acquire a migratory behavior, allowing them to move away from their epithelial
      cell community and to integrate into surrounding tissue, even at remote
      locations. EMT illustrates the differentiation plasticity during development and
      is complemented by another process, called mesenchymal to epithelial transition
      (MET). While being an integral process during development, EMT is also
      recapitulated under pathological conditions, prominently in fibrosis and in
      invasion and metastasis of carcinomas. Accordingly, EMT is considered as an
      important step in tumor progression. TGF-beta signaling has been shown to play an
      important role in EMT. In fact, adding TGF-beta to epithelial cells in culture is
      a convenient way to induce EMT in various epithelial cells. Although much less
      characterized, epithelial plasticity can also be regulated by TGF-beta-related
      bone morphogenetic proteins (BMPs), and BMPs have been shown to induce EMT or MET
      depending on the developmental context. In this review, we will discuss the
      induction of EMT in response to TGF-beta, and focus on the underlying signaling
      and transcription mechanisms.

PMID- 19153599
TI  - Lysine 63-linked polyubiquitin chain may serve as a targeting signal for the 26S
      proteasome.
AB  - Recruitment of substrates to the 26S proteasome usually requires covalent
      attachment of the Lys48-linked polyubiquitin chain. In contrast, modifications
      with the Lys63-linked polyubiquitin chain and/or monomeric ubiquitin are
      generally thought to function in proteasome-independent cellular processes.
      Nevertheless, the ubiquitin chain-type specificity for the proteasomal targeting
      is still poorly understood, especially in vivo. Using mass spectrometry, we found
      that Rsp5, a ubiquitin-ligase in budding yeast, catalyzes the formation of Lys63
      linked ubiquitin chains in vitro. Interestingly, the 26S proteasome degraded well
      the Lys63-linked ubiquitinated substrate in vitro. To examine whether Lys63
      linked ubiquitination serves in degradation in vivo, we investigated the
      ubiquitination of Mga2-p120, a substrate of Rsp5. The polyubiquitinated p120
      contained relatively high levels of Lys63-linkages, and the Lys63-linked chains
      were sufficient for the proteasome-binding and subsequent p120-processing. In
      addition, Lys63-linked chains as well as Lys48-linked chains were detected in the
      26S proteasome-bound polyubiquitinated proteins. These results raise the
      possibility that Lys63-linked ubiquitin chain also serves as a targeting signal
      for the 26S proteaseome in vivo.

PMID- 19153600
TI  - Recruitment of a chromatin remodelling complex by the Hog1 MAP kinase to stress
      genes.
AB  - For efficient transcription, RNA PolII must overcome the presence of nucleosomes.
      The p38-related MAPK Hog1 is an important regulator of transcription upon
      osmostress in yeast and thereby it is involved in initiation and elongation.
      However, the role of this protein kinase in elongation has remained unclear.
      Here, we show that during stress there is a dramatic change in the nucleosome
      organization of stress-responsive loci that depends on Hog1 and the RSC chromatin
      remodelling complex. Upon stress, the MAPK Hog1 physically interacts with RSC to
      direct its association with the ORF of osmo-responsive genes. In RSC mutants,
      PolII accumulates on stress promoters but not in coding regions. RSC mutants also
      display reduced stress gene expression and enhanced sensitivity to osmostress.
      Cell survival under acute osmostress might thus depend on a burst of
      transcription that in turn could occur only with efficient nucleosome eviction.
      Our results suggest that the selective targeting of the RSC complex by Hog1
      provides the necessary mechanistic basis for this event.

PMID- 19153601
TI  - Estrogenic GPR30 signalling induces proliferation and migration of breast cancer
      cells through CTGF.
AB  - The steroid hormone oestrogen can signal through several receptors and pathways.
      Although the transcriptional responses mediated by the nuclear oestrogen
      receptors (ER) have been extensively characterized, the changes in gene
      expression elicited by signalling through the membrane-associated ER GPR30 have
      not been studied. We show here for ER-negative human breast cancer cells that the
      activation of GPR30 signalling by oestrogen or by hydroxytamoxifen (OHT), an ER
      antagonist but GPR30 agonist, induces a transcription factor network, which
      resembles that induced by serum in fibroblasts. The most strongly induced gene,
      CTGF, appears to be a target of these transcription factors. We found that the
      secreted factor connective tissue growth factor (CTGF) not only contributes to
      promote proliferation but also mediates the GPR30-induced stimulation of cell
      migration. These results provide a framework for understanding the physiological
      and pathological functions of GPR30. As the activation of GPR30 by OHT also
      induces CTGF in fibroblasts from breast tumour biopsies, these pathways may be
      involved in promoting aggressive behaviour of breast tumours in response to
      endogenous oestrogens or to OHT being used for endocrine therapy.

PMID- 19153602
TI  - Replication protein A (AtRPA1a) is required for class I crossover formation but
      is dispensable for meiotic DNA break repair.
AB  - Replication protein A (RPA) is involved in many aspects of DNA metabolism
      including meiotic recombination. Many species possess a single RPA1 gene but
      Arabidopsis possesses five RPA1 paralogues. This feature has enabled us to gain
      further insight into the meiotic role of RPA1. Proteomic analysis implicated one
      of the AtRPA1 family (AtRPA1a) in meiosis. Immunofluorescence studies confirmed
      that AtRPA1a is associated with meiotic chromosomes from leptotene through to
      early pachytene. Analysis of an Atrpa1a mutant revealed that AtRPA1a is not
      essential at early stages in the recombination pathway. DNA double-strand breaks
      are repaired in Atrpa1a, but the mutant is defective in the formation of
      crossovers, exhibiting a 60% reduction in chiasma frequency. Consistent with
      this, localization of recombination proteins AtRAD51 and AtMSH4 appears normal,
      whereas the numbers of AtMLH1 and AtMLH3 foci at pachytene are significantly
      reduced. This suggests that the defect in Atrpa1a is manifested at the stage of
      second-end capture. Analysis of Atrpa1a/Atmsh4 and Atrpa1a/Atmlh3 double mutants
      indicates that loss of AtRPA1a predominantly affects the formation of class I,
      interference-dependent crossovers.

PMID- 19153603
TI  - Raf kinase inhibitory protein suppresses a metastasis signalling cascade
      involving LIN28 and let-7.
AB  - Raf kinase inhibitory protein (RKIP) negatively regulates the MAP kinase (MAPK),
      G protein-coupled receptor kinase-2, and NF-kappaB signalling cascades. RKIP has
      been implicated as a metastasis suppressor for prostate cancer, but the mechanism
      is not known. Here, we show that RKIP inhibits invasion by metastatic breast
      cancer cells and represses breast tumour cell intravasation and bone metastasis
      in an orthotopic murine model. The mechanism involves inhibition of MAPK, leading
      to decreased transcription of LIN28 by Myc. Suppression of LIN28 enables enhanced
      let-7 processing in breast cancer cells. Elevated let-7 expression inhibits
      HMGA2, a chromatin remodelling protein that activates pro-invasive and pro
      metastatic genes, including Snail. LIN28 depletion and let-7 expression suppress
      bone metastasis, and LIN28 restores bone metastasis in mice bearing RKIP
      expressing breast tumour cells. These results indicate that RKIP suppresses
      invasion and metastasis in part through a signalling cascade involving MAPK, Myc,
      LIN28, let-7, and downstream let-7 targets. RKIP regulation of two pluripotent
      stem cell genes, Myc and LIN28, highlights the importance of RKIP as a key
      metastasis suppressor and potential therapeutic agent.

PMID- 19153604
TI  - Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin
      3.
AB  - Deubiquitinating enzymes (DUBs) control the ubiquitination status of proteins in
      various cellular pathways. Regulation of the activity of DUBs, which is
      critically important to cellular homoeostasis, can be achieved at the level of
      gene expression, protein complex formation, or degradation. Here, we report that
      ubiquitination also directly regulates the activity of a DUB, ataxin-3, a
      polyglutamine disease protein implicated in protein quality control pathways.
      Ubiquitination enhances ubiquitin (Ub) chain cleavage by ataxin-3, but does not
      alter its preference for K63-linked Ub chains. In cells, ubiquitination of
      endogenous ataxin-3 increases when the proteasome is inhibited, when excess Ub is
      present, or when the unfolded protein response is induced, suggesting that the
      cellular functions of ataxin-3 in protein quality control are modulated through
      ubiquitination. Ataxin-3 is the first reported DUB in which ubiquitination
      directly regulates catalytic activity. We propose a new function for protein
      ubiquitination in regulating the activity of certain DUBs and perhaps other
      enzymes.

PMID- 19153605
TI  - Structure of the F-spondin domain of mindin, an integrin ligand and pattern
      recognition molecule.
AB  - Mindin (spondin-2) is an extracellular matrix protein of unknown structure that
      is required for efficient T-cell priming by dendritic cells. Additionally, mindin
      functions as a pattern recognition molecule for initiating innate immune
      responses. These dual functions are mediated by interactions with integrins and
      microbial pathogens, respectively. Mindin comprises an N-terminal F-spondin (FS)
      domain and C-terminal thrombospondin type 1 repeat (TSR). We determined the
      structure of the FS domain at 1.8-A resolution. The structure revealed an eight
      stranded antiparallel beta-sandwich motif resembling that of membrane-targeting
      C2 domains, including a bound calcium ion. We demonstrated that the FS domain
      mediates integrin binding and identified the binding site by mutagenesis. The
      mindin FS domain therefore represents a new integrin ligand. We further showed
      that mindin recognizes lipopolysaccharide (LPS) through its TSR domain, and
      obtained evidence that C-mannosylation of the TSR influences LPS binding. Through
      these dual interactions, the FS and TSR domains of mindin promote activation of
      both adaptive and innate immune responses.

PMID- 19153606
TI  - Two-polymerase mechanisms dictate error-free and error-prone translesion DNA
      synthesis in mammals.
AB  - DNA replication across blocking lesions occurs by translesion DNA synthesis
      (TLS), involving a multitude of mutagenic DNA polymerases that operate to protect
      the mammalian genome. Using a quantitative TLS assay, we identified three main
      classes of TLS in human cells: two rapid and error-free, and the third slow and
      error-prone. A single gene, REV3L, encoding the catalytic subunit of DNA
      polymerase zeta (pol zeta), was found to have a pivotal role in TLS, being
      involved in TLS across all lesions examined, except for a TT cyclobutane dimer.
      Genetic epistasis siRNA analysis indicated that discrete two-polymerase
      combinations with pol zeta dictate error-prone or error-free TLS across the same
      lesion. These results highlight the central role of pol zeta in both error-prone
      and error-free TLS in mammalian cells, and show that bypass of a single lesion
      may involve at least three different DNA polymerases, operating in different two
      polymerase combinations.

PMID- 19153607
TI  - Structural basis for translational inhibition by the tumour suppressor Pdcd4.
AB  - Pdcd4 is a tumour suppressor protein. It inhibits translation through interaction
      with translation initiator eIF4A, resulting in the suppression of neoplastic
      transformation and tumour invasion. Here, we present the crystal structures of an
      N-terminal-truncated Pdcd4 in free form and in complex with eIF4A. Upon binding
      to eIF4A, Pdcd4 undergoes a marked conformational change to form a heterotrimeric
      complex with eIF4A, with one Pdcd4 binding to two eIF4A molecules in two
      different modes. The binding of Pdcd4 to eIF4A is required to inhibit the
      enzymatic activity of eIF4A, translation initiation, and AP-1-dependent
      transcription. Both MA3 domains are required to efficiently compete with the C
      terminal domain of eIF4G (eIF4Gc) for binding to eIF4A whereas a single MA3 is
      sufficient to inhibit translation. Our structural and mutational analyses reveal
      that Pdcd4 inhibits translation initiation by trapping eIF4A in an inactive
      conformation, and blocking its incorporation into the eIF4F complex.

PMID- 19153608
TI  - TRPP2 channels regulate apoptosis through the Ca2+ concentration in the
      endoplasmic reticulum.
AB  - Ca(2+) is an important signalling molecule that regulates multiple cellular
      processes, including apoptosis. Although Ca(2+) influx through transient receptor
      potential (TRP) channels in the plasma membrane is known to trigger cell death,
      the function of intracellular TRP proteins in the regulation of Ca(2+)-dependent
      signalling pathways and apoptosis has remained elusive. Here, we show that TRPP2,
      the ion channel mutated in autosomal dominant polycystic kidney disease (ADPKD),
      protects cells from apoptosis by lowering the Ca(2+) concentration in the
      endoplasmic reticulum (ER). ER-resident TRPP2 counteracts the activity of the
      sarcoendoplasmic Ca(2+) ATPase by increasing the ER Ca(2+) permeability. This
      results in diminished cytosolic and mitochondrial Ca(2+) signals upon stimulation
      of inositol 1,4,5-trisphosphate receptors and reduces Ca(2+) release from the ER
      in response to apoptotic stimuli. Conversely, knockdown of TRPP2 in renal
      epithelial cells increases ER Ca(2+) release and augments sensitivity to
      apoptosis. Our findings indicate an important function of ER-resident TRPP2 in
      the modulation of intracellular Ca(2+) signalling, and provide a molecular
      mechanism for the increased apoptosis rates in ADPKD upon loss of TRPP2 channel
      function.

PMID- 19153609
TI  - Structure, interaction and real-time monitoring of the enzymatic reaction of wild
      type APOBEC3G.
AB  - Human APOBEC3G exhibits anti-human immunodeficiency virus-1 (HIV-1) activity by
      deaminating cytidines of the minus strand of HIV-1. Here, we report a solution
      structure of the C-terminal deaminase domain of wild-type APOBEC3G. The
      interaction with DNA was examined. Many differences in the interaction were found
      between the wild type and recently studied mutant APOBEC3Gs. The position of the
      substrate cytidine, together with that of a DNA chain, in the complex, was
      deduced. Interestingly, the deamination reaction of APOBEC3G was successfully
      monitored using NMR signals in real time. Real-time monitoring has revealed that
      the third cytidine of the d(CCCA) segment is deaminated at an early stage and
      that then the second one is deaminated at a late stage, the first one not being
      deaminated at all. This indicates that the deamination is carried out in a strict
      3' --> 5' order. Virus infectivity factor (Vif) of HIV-1 counteracts the anti-HIV
      1 activity of APOBEC3G. The structure of the N-terminal domain of APOBEC3G, with
      which Vif interacts, was constructed with homology modelling. The structure
      implies the mechanism of species-specific sensitivity of APOBEC3G to Vif action.

PMID- 19153610
TI  - Regulation of Notch and Wingless signalling by phyllopod, a transcriptional
      target of the EGFR pathway.
AB  - Spatial and temporal control of Notch and Wingless (Wg) pathways during
      development is regulated at multiple levels. Here, we present an analysis of
      Phyllopod as a coordinated regulator of these two critical signal transduction
      pathways. Phyl specifically helps traffic Notch and Wg pathway components within
      early endocytic vesicles, thereby controlling the amount of processed signal
      available for causing a transcriptional response within the nucleus. In
      Drosophila, the EGFR pathway transcriptionally activates phyl whose product then
      blocks Notch and Wg signalling pathways. This provides a mechanistic basis for an
      antagonistic relationship between receptor tyrosine kinase and Notch/Wg pathways
      during development. Furthermore, this study identifies a Phyl-regulated class of
      endosomal vesicles that specifically include components of Notch and Wg
      signalling.

PMID- 19153611
TI  - Differential targeting of Tetrahymena ORC to ribosomal DNA and non-rDNA
      replication origins.
AB  - The Tetrahymena thermophila origin recognition complex (ORC) contains an integral
      RNA subunit, 26T RNA, which confers specificity to the amplified ribosomal DNA
      (rDNA) origin by base pairing with an essential cis-acting replication
      determinant--the type I element. Using a plasmid maintenance assay, we identified
      a 6.7 kb non-rDNA fragment containing two closely associated replicators, ARS1-A
      (0.8 kb) and ARS1-B (1.2 kb). Both replicators lack type I elements and hence
      complementarity to 26T RNA, suggesting that ORC is recruited to these sites by an
      RNA-independent mechanism. Consistent with this prediction, although ORC
      associated exclusively with origin sequences in the 21 kb rDNA minichromosome,
      the interaction between ORC and the non-rDNA ARS1 chromosome changed across the
      cell cycle. In G(2) phase, ORC bound to all tested sequences in a 60 kb interval
      spanning ARS1-A/B. Remarkably, ORC and Mcm6 associated with just the ARS1-A
      replicator in G(1) phase when pre-replicative complexes assemble. We propose that
      ORC is stochastically deposited onto newly replicated non-rDNA chromosomes and
      subsequently targeted to preferred initiation sites prior to the next S phase.

PMID- 19153613
TI  - Plant MTs-long neglected members of the metallothionein superfamily.
AB  - Occurrence of metallothioneins (MTs) was initially thought to be restricted to
      the animal kingdom, and the corresponding functions such as detoxification of
      heavy metal ions were assumed to be taken over in plants by the enzymatically
      synthesized phytochelatins. This perception was revised in the past years, and
      the existence of plant metallothioneins is generally accepted. Compared to the
      vertebrate forms, members of the plant MT family display a significantly larger
      sequence diversity, however, surprisingly little information is available
      concerning their possible functions, properties, and structures. Gene expression
      studies, and thus studies on the mRNA level, are the major source of data aiming
      at elucidating the function of plant MTs. However, so far it is not possible to
      unambiguously assign a specific function to a given metallothionein as proposed
      functions overlap, are complementary to each other, or even contradictory results
      are obtained. With respect to the structures and properties of plant
      metallothioneins even less scientific contributions are available illustrating
      the early stages, in which this research area resides. Existing data covers the
      metal ion content of the different plant metallothionein species and the pH
      stabilities of the resulting metal-thiolate clusters. Further, for a limited
      selection of proteins the number of clusters formed has been proposed and
      predictions towards the secondary structure of the protein backbone made. A
      recently determined three-dimensional structure of the larger domain of the wheat
      metallothionein E(c)-1 describes a metal ion coordination mode unprecedented for
      any metallothionein so far.

PMID- 19153612
TI  - Ciliary targeting motif VxPx directs assembly of a trafficking module through
      Arf4.
AB  - Dysfunctions of primary cilia and cilia-derived sensory organelles underlie a
      multitude of human disorders, including retinal degeneration, yet membrane
      targeting to the cilium remains poorly understood. Here, we show that the newly
      identified ciliary targeting VxPx motif present in rhodopsin binds the small
      GTPase Arf4 and regulates its association with the trans-Golgi network (TGN),
      which is the site of assembly and function of a ciliary targeting complex. This
      complex is comprised of two small GTPases, Arf4 and Rab11, the Rab11/Arf effector
      FIP3, and the Arf GTPase-activating protein ASAP1. ASAP1 mediates GTP hydrolysis
      on Arf4 and functions as an Arf4 effector that regulates budding of post-TGN
      carriers, along with FIP3 and Rab11. The Arf4 mutant I46D, impaired in ASAP1
      mediated GTP hydrolysis, causes aberrant rhodopsin trafficking and cytoskeletal
      and morphological defects resulting in retinal degeneration in transgenic
      animals. As the VxPx motif is present in other ciliary membrane proteins, the
      Arf4-based targeting complex is most likely a part of conserved machinery
      involved in the selection and packaging of the cargo destined for delivery to the
      cilium.

PMID- 19153614
TI  - N-Heterocyclic carbenes/imidazolium salts as substrates in catalysis: the
      catalytic 2-substitution and annulation of heterocyclic compounds.
AB  - N-Heterocyclic carbenes (NHCs) are commonly regarded as strong donor ligands that
      are valuable in coordination chemistry and catalysis. Many reports describing
      this aspect of their chemistry have been published. The alternative view of NHCs
      as reaction intermediates has been little explored, and yet excellent examples
      exist and will be reviewed in this perspective. Group 10 hydrocarbyl complexes of
      NHCs [(R)(NHC)ML(2) where R = H, alkyl, aryl, acyl; M = Ni, Pd, Pt] undergo a
      facile reductive elimination to generate M(0) and R-substituted-azolium salt as
      products. On the other hand, 2-Hazolium salts will oxidatively add to M(0)
      complexes to afford reactive NHC-M-H compounds, suitable as catalysts for
      selected reactions. Combining the oxidative addition and reductive elimination
      steps into a single cycle, in the presence of an alkene, provides of a novel and
      potentially exciting, atom efficient catalytic C-C bond forming process for the
      substitution, and annulation of heterocyclic rings.

PMID- 19153615
TI  - Activation of B-H bonds by an oxo-rhenium complex.
AB  - The isolation and structural characterization by X-ray diffraction of
      (PPh(3))(2)(O)(I)Re(H)OBcat and (PPh(3))(2)(O)(I)Re(H)OBpin from the reaction of
      ReIO(2)(PPh(3))(2) with the boranes catecholborane (HBcat) and pinacolborane
      (HBpin) unequivocally shows the first example of activation of B-H bond by a high
      valent oxo-rhenium complex.

PMID- 19153616
TI  - A low-coordinate nickel(ii) hydride complex and its reactivity.
AB  - The preparation of a novel dinuclear nickel(ii) hydride complex and its
      reactivity that often leads to nickel(i) compounds is described.

PMID- 19153617
TI  - Carbonyl-ruthenium substituted alpha-Keggin-tungstosilicate, [alpha
      SiW(11)O(39)Ru(II)(CO)](6-): synthesis, structure, redox studies and reactivity.
AB  - The carbonyl-ruthenium substituted undecatungstosilicate [alpha
      SiW(11)O(39)Ru(II)(CO)](6-) () was isolated as a caesium salt and successfully
      characterized by using (183)W and (13)C NMR, elemental analysis, IR, UV-vis and
      cyclic voltammetry (CV). Polyanion represents the first example of a metal
      carbonyl moiety being fully incorporated into the polyoxometalate (POM). As a
      result, the Ru(CO) moiety became redox active and was reversibly oxidized to the
      one-electron ruthenium(iii) derivative, [alpha-SiW(11)O(39)Ru(III)(CO)](5-). This
      Ru(III)(CO) moiety was unexpectedly stable in aqueous solution compared to the
      organo-ruthenium carbonyl derivatives and could be detected by using UV-vis and
      in situ IR coupled with electrolysis. The oxidized ruthenium(iii) derivative
      slowly released CO in aqueous solution, resulting in the aqua species [alpha
      SiW(11)O(39)Ru(III)(H(2)O)](5-) and then the dimeric POM species by condensation.
      Furthermore, could be converted to the corresponding aqua polyanion by photo
      irradiation.

PMID- 19153618
TI  - Ru(III)-based compounds with sulfur donor ligands: synthesis, characterization,
      electrochemical behaviour and anticancer activity.
AB  - In recent years, Ru(iii) complexes have emerged as a new class of effective
      anticancer agents against tumors that proved to be resistant to all other
      chemotherapeutic drugs currently in clinical use. To extend our previous studies
      on metal complexes containing sulfur-donor ligands, we report here on the
      synthesis and characterization, by means of several spectroscopic and analytical
      techniques, some [Ru(RSDT)(3)] and [Ru(2)(RSDT)(5)]Cl complexes with
      dithiocarbamato ligands derived from methyl/ethyl/tert-butyl esters of sarcosine.
      Their electrochemical behaviour was also studied by cyclic voltammetry. All the
      complexes were tested for their cytotoxicity on a panel of human tumor cell lines
      showing highly significant antitumor activity. The chemical and biological
      properties of the newly synthesized complexes, were compared with those of
      [Ru(DMDT)(3)] and [Ru(2)(DMDT)(5)]Cl species (DMDT = N,N-dimethyldithiocarbamate)
      whose chemical (not biological) characterization has been already reported in
      literature.

PMID- 19153619
TI  - Synthesis of Pd complexes directly linked to the light-absorbing [(bpy)(3)Ru](2+)
      unit and their photochemical reactions toward styrenes.
AB  - A series of bipyridyl-Pd and Rh complexes containing a [(bpy)(3)Ru](2+) or
      [(bpy)(2)Ru(phen)](2+) (bpy = 2,2'-bipyridyl, phen = 1,10-phenanthroline) moiety
      as visible-light absorbing unit was synthesized. The complexes were synthesized
      via a Suzuki-Miyaura coupling reaction between the Ru complexes having a 4-bromo
      2,2'-bipyridyl ligand and a 2,2'-bipyridyl-4-boronic acid and a subsequent
      reaction with various mononuclear Pd and Rh precursors. There was a noticeable
      structural difference between the QP (2,2':4',4'':2'',2'''-quaterpyridyne) and PB
      (5-(2,2'-bipyridyl)-yl-1,10-phenanthroline) complexes, which involved the
      dihedral angles within the bridging ligand; the PB complexes possessed large
      dihedral angles but the QP complexes showed small values. This structural
      difference clearly indicated a strong pi-conjugation through the QP ligand. The
      electrochemical and photophysical properties of the QP and PB complexes were
      compared with the parent mononuclear Ru complexes, such as [(bpy)(3)Ru](2+),
      [(bpy)(2)Ru(phen)](2+), and [(bpy)(2)Ru(bpm)](2+) (bpm = 2,2'-bipyrimidine). The
      QP and PB complexes showed a (3)MLCT life time that was similar to
      [(bpy)(3)Ru](2+) and [(bpy)(2)Ru(phen)](2+), which was about 10 times longer (ca.
      1 mus) than the corresponding bpm complexes. Reactivity studies with Pd complexes
      toward styrene dimerizations were examined. The reaction proceeded under visible
      light irradiated conditions and the reactivity of the QP complexes was much
      higher than the corresponding PB complexes. Substantial acceleration of the
      reaction was observed with the introduction of an Me substituent on the bipyridyl
      ligand.

PMID- 19153620
TI  - Controlling the extent of pi-backbonding in platinum(ii) terpyridyl systems: a
      detailed kinetic, mechanistic and computational approach.
AB  - The rate of substitution of the chloride ligand from [Pt(terpy)Cl](+) () (where
      terpy = 2,2':6',2''-terpyridine) and its corresponding analogue
      [Pt((t)Bu(3)terpy)Cl](+) () (where (t)Bu(3)terpy = 4,4',4''-tri-tert-butyl
      2,2':6',2''-terpyridine) by a series of neutral and anionic nucleophiles, viz.
      thiourea (TU), 1,3-dimethyl-2-thiourea (DMTU), 1,1,3,3-tetramethyl-2-thiourea
      (TMTU), iodide (I(-)) and thiocyanate (SCN(-)), was determined under pseudo first
      order conditions as a function of concentration and temperature using standard
      stopped-flow spectrophotometric techniques. The observed pseudo first-order rate
      constants for the substitution reactions obeyed the simple rate law k(obs) =
      k(2)[nucleophile]. Second-order kinetics and negative activation entropies
      support an associative mode of activation. The rate of substitution of chloride
      is observed to decrease with an increase in the steric bulk of the neutral
      nucleophiles, whilst rate of substitution by I(-) was observed to be faster than
      that by SCN(-), in correlation with their polarizability and the softness of the
      metal centre. A comparison of the second-order rate constants, k(2), at 298 K,
      obtained for the substitution reactions of and shows that the introduction of
      strong sigma-donating groups on the periphery of the terpyridyl backbone in
      results in a corresponding decrease in the reactivity. DFT calculations at the
      B3LYP/LACVP** level of theory for the two complexes, and , and a series of
      similar analogues containing either electron-donating or electron-withdrawing
      groups in the periphery positions demonstrate that the introduction of electron
      donating groups decreases the positive charge on the metal centre and increases
      energy separation of the frontier molecular orbitals (E(HOMO)-E(LUMO)) of the
      ground state platinum(ii) complexes leading to a less reactive metal centre
      whilst the introduction of electron-withdrawing groups has an opposite effect
      leading to increased reactivity of the metal centre.

PMID- 19153621
TI  - Metalloporphyrin anion sensors: the effect of the metal centre on the anion
      binding properties of amide-functionalised and tetraphenyl metalloporphyrins.
AB  - This article describes the synthesis and anion binding properties of a series of
      'picket fence' metalloporphyrin complexes, within which the metal centre is
      systematically varied. The porphyrin structure contains four amide bonds and is
      the same for each metal. The anion binding properties of these receptors are
      further contrasted with those of their tetraphenylporphyrin congeners to
      elucidate both the effect of the metal centre and the influence of the amide
      groups on the anion recognition process. Anion binding was demonstrated using
      UV/visible and (1)H NMR spectroscopies, electrochemistry and luminescence. The
      metal centre was found to be highly influential in the strength and selectivity
      of binding; for example, the cadmium and mercury complexes exhibited far greater
      affinities for anions than the zinc complexes in competitive solvents such as
      DMSO. The amide functionalities were found to enhance the anion binding process.

PMID- 19153622
TI  - Curly-curly, loop-loop: homoleptic metal(ii) complexes of pyridinecarbaldehyde 4'
      (2,2':6',2''-terpyridyl)hydrazones and their coordination polymers.
AB  - The ligands 4-, 3- and 2-pyridinecarbaldehyde 4'-(2,2':6',2''
      terpyridyl)hydrazone (, and ) have been prepared and characterized. In the
      homoleptic iron(ii) and ruthenium(ii) complexes, the nitrogen donor atoms of the
      pendant pyridine rings subtend an obtuse angle ( approximately 155 degrees ) at
      the metal centre, thus providing an expanded ligand, which can be used for the
      assembly one-dimensional coordination polymers with an undulating backbone.
      Protonation of the pendant pyridine rings in [FeL(2)](2+) (L = , , ) or
      [RuL(2)](2+) (L = , ) leads to a colour change from purple to blue, or red to
      pink, respectively, as the MLCT band shifts to a lower energy. The structural
      data for [Fe(H)()][PF(6)](3).3.5MeCN.2.5H(2)O (where [H](+) is the monoprotonated
      ligand) show that the [Fe(H)()](3+) cations form one-dimensional chains supported
      by N(py)HN(py) hydrogen bonds and that the undulating chains pack to give a
      porous material, with channels that accommodate the anions and solvent molecules.
      A single-crystal X-ray diffraction determination of
      {[Fe(NCS)(2)(Ru()(2))(2)][Fe(2)(NCS)(6)(OEt)(2)(EtOH)(2)][NCS](2).4EtOH.H(2)O}(n)
      reveals that pairs of [Ru()(2)](2+) cations connect {Fe(NCS)(2)} units to give a
      one-dimensional polymer comprising of linked metallamacrocycles.

PMID- 19153623
TI  - Wiring terpyridine: approaches to alkynylthienyl 2,2':6',2''-terpyridines.
AB  - The reaction of triisopropylsilylethyne or trimethylsilylethyne with 4'-(5-bromo
      2-thienyl)-2,2':6',2''-terpyridine () leads to 4'-(5-triisopropylsilylethynyl-2
      thienyl)-2,2':6',2''-terpyridine () or 4'-(5-trimethylsilylethynyl-2-thienyl)
      2,2':6',2''-terpyridine (). The latter compound may be deprotected to give 4'-(5
      ethynyl-2-thienyl)-2,2':6',2''-terpyridine (). Treatment of the complexes
      [Ru()(2)][PF(6)](2), [Ru(tpy)()][PF(6)](2) and [Ru()(2)][PF(6)](2) ( = 4'-(4
      bromo-2-thienyl)-2,2':6',2''-terpyridine) with triisopropylsilylethyne yields the
      corresponding homoleptic and heteroleptic alkynylthienyl-terminated ruthenium(ii)
      complexes, for which spectroscopic and electrochemical data are presented. The
      reaction of [RuCl(2)(DMSO)(4)] with leads to [Ru()(2)][PF(6)](2), in which the
      tpy ligands bear conjugated thienyl and alkynyl groups; the latter can also be
      accessed by deprotection of [Ru()(2)][PF(6)](2). The single-crystal structures of
      ligands and , and of [Ru()(tpy)][BPh(4)](2).1.3MeCN,
      [Ru()(2)][PF(6)](2).2MeNO(2), 2{[Ru()(2)][PF(6)](2)}.5MeCN, [Ru()(2)][PF(6)](2)
      and [Ru()(2)][PF(6)](2).MeCN are presented, and among the homoleptic complexes,
      pi-stacking interactions between thiophene and pyridine rings leading to pairs of
      associated cations provide a common structural motif.

PMID- 19153624
TI  - Some transition metal complexes derived from mono- and di-ethynyl
      perfluorobenzenes.
AB  - Transition metal alkynyl complexes containing perfluoroaryl groups have been
      prepared directly from trimethylsilyl-protected mono- and di-ethynyl
      perfluoroarenes by simple desilylation/metallation reaction sequences. Reactions
      between Me(3)SiC[triple bond, length as m-dash]CC(6)F(5) and RuCl(dppe)Cp' [Cp' =
      Cp, Cp*] in the presence of KF in MeOH give the monoruthenium complexes
      Ru(C[triple bond, length as m-dash]CC(6)F(5))(dppe)Cp' [Cp' = Cp (); Cp* ()],
      which are related to the known compound Ru(C[triple bond, length as m
      dash]CC(6)F(5))(PPh(3))(2)Cp (). Treatment of Me(3)SiC[triple bond, length as m
      dash]CC(6)F(5) with Pt(2)(mu-dppm)(2)Cl(2) in the presence of NaOMe in MeOH gave
      the bis(alkynyl) complex Pt(2)(mu-dppm)(2)(C[triple bond, length as m
      dash]CC(6)F(5))(2) (). The Pd(0)/Cu(i)-catalysed reactions between Au(C[triple
      bond, length as m-dash]CC(6)F(5))(PPh(3)) and Mo( identical withCBr)(CO)(2)Tp*
      [Tp* = hydridotris(3.5-dimethylpyrazoyl)borate], Co(3)(mu(3)-CBr)(mu-dppm)(CO)(7)
      or IC[triple bond, length as m-dash]CFc [Fc = (eta(5)-C(5)H(4))FeCp] afford Mo(
      identical withCC[triple bond, length as m-dash]CC(6)F(5))(CO)(2)Tp* (),
      Co(3)(mu(3)-CC[triple bond, length as m-dash]CC(6)F(5))(mu-dppm)(CO)(7) () and
      FcC[triple bond, length as m-dash]CC[triple bond, length as m-dash]CC(6)F(5) (),
      respectively. The diruthenium complexes 1,4-{Cp'(PP)RuC[triple bond, length as m
      dash]C}(2)C(6)F(4) [(PP)Cp' = (PPh(3))(2)Cp (); (dppe)Cp (); (dppe)Cp* ()] are
      prepared from 1,4-(Me(3)SiC[triple bond, length as m-dash]C)(2)C(6)F(4) in a
      manner similar to that described for the monoruthenium complexes -. The non
      fluorinated complexes 1,4-{Cp'(PP)RuC[triple bond, length as m-dash]C}(2)C(6)H(4)
      [(PP)Cp' = (PPh(3))(2)Cp (); (dppe)Cp (); (dppe)Cp* ()], prepared for comparison,
      are obtained from 1,4-(Me(3)SiC[triple bond, length as m-dash]C)(2)C(6)H(4).
      Spectro-electrochemical studies of the ruthenium aryl and arylene alkynyl
      complexes - and -, together with DFT-based computational studies on suitable
      model systems, indicate that perfluorination of the aromatic ring has little
      effect on the electronic structures of these compounds, and that the frontier
      orbitals have appreciable diethynylphenylene character. Molecular structure
      determinations are reported for the fluoroaromatic complexes , , , and .

PMID- 19153625
TI  - Pentadentate thiosemicarbazones as versatile chelating systems. A comparative
      structural study of their metallic complexes.
AB  - We have prepared some transition and post-transition metal complexes derived from
      the pentadentate thiosemicarbazone ligand bis(4-N-ethylthiosemicarbazone)-2,6
      diacetylpyridine H(2)L(Et), by both chemical and electrochemical procedures. The
      complexes have been synthesised and fully characterised, including the crystal
      structures for the ligand H(2)L(Et) and its manganese, cadmium and lead
      complexes. We have also performed multinuclear (109)Ag, (113)Cd, (119)Sn and
      (207)Pb studies for silver, cadmium, tin and lead compounds, respectively.
      Moreover we present here a comparative study on the different structures found
      for pentadentate thiosemicarbazonate complexes, trying to check the influence of
      different factors, such as experimental procedure, size of metal, structure of
      the ligand, and metal oxidation state, on the final structure of the complex
      formed. Our aim is gaining a better insight into the coordination trends of
      pentadentate thiosemicarbazone ligands.

PMID- 19153626
TI  - Subtle structural variation in copper metal-organic frameworks: syntheses,
      structures, magnetic properties and catalytic behaviour.
AB  - Two new copper metal-organic frameworks containing 5-nitro-1,3
      benzenedicarboxylate (5-nbdc) have been prepared from the reaction between
      Cu(NO(3))(2).3H(2)O and H(2)(5-nbdc) in DMF at different temperatures. Single
      crystal X-ray structures of {[Cu(2)(5-nbdc)(2)(DMF)(2)].2DMF}(infinity) () and
      {[Cu(2)(5-nbdc)(2)(DMF)(2)].3(1/3)DMF}(infinity) () revealed similar sheet
      structures, containing triangular and hexagonal pores, but differences in the
      stacking of the sheets. Magnetic measurements on and are consistent with
      antiferromagnetic dimers containing a small quantity of paramagnetic impurity.
      The desolvated forms of and were applied as Lewis acid catalysts in the
      acetylation of methyl 4-hydroxybenzoate. When the reaction between
      Cu(NO(3))(2).3H(2)O and H(2)(5-nbdc) was carried out in a mixture of DMF and
      water, the reaction gave metallomacrocycles of formula [Cu(6)(5
      nbdc)(6)(H(2)O)(12)(DMF)(6)] (). These assemble through hydrogen-bonding
      interactions to form a gross structure in which the macrocycle pores align into
      channels. The reaction between Cu(NO(3))(2).3H(2)O and 5-methylsulfanylmethyl-1,3
      benzenedicarboxylic acid, H(2)(5-msbdc), in DMF-water gave {[Cu(2)(5
      msbdc)(2)(OH(2))(2)].3DMF}(infinity) (), which contains similar sheets to those
      in and , whereas the reaction with 5-amino-1,3-benzenedicarboxylic acid, H(2)(5
      abdc), gave {[Cu(2)(5-abdc)(2)(DMF)(2)]}(infinity) (), which has a previously
      reported network based on sheets containing rhombohedral pores. The reaction
      between Cu(NO(3))(2).3H(2)O and 2-methoxy-1,3-benzenedicarboxylic acid, H(2)(2
      mbdc), in DMF gave [Cu(2)(2-mbdc)(2)(DMF)(2)] (). The presence of the substituent
      in the 2-position removes the co-planarity of the carboxylate groups, and the
      sheet structure adopted by contains rhomboidal pores.

PMID- 19153628
TI  - First stable reduced form of [Co(5)](+10): fine tuning of linear pentacobalt(ii)
      complexes containing delocalized metal-metal bonds through ligand modification.
AB  - Pentacobalt EMACs [Co(5)(mu(5)-dpzpda)(4)X(2)] (X = Cl(-) (), NCS(-) ()) with
      fine-tuning of the supporting ligand based on the tripyridyldiamine ligand, N,N'
      di(pyrazin-2-yl)pyridine-2,6-diamine (H(2)dpzpda), and their reduced form
      (Ph(4)P)[Co(5)(mu(5)-dpzpda)(4)X(2)] (X = Cl(-) (), NCS(-) ()) were first
      synthesized and structurally characterized. The structures of showed direct Co-Co
      bonds with Co-Co distances in the range 2.2385(7)-2.2888(15) A, and valence
      electrons delocalized through the whole metal chain with distances of longer than
      9.06 A. The distances of the inner Co-Co bonds and the Co-axial ligands became
      longer after reduction, whereas no significant change was observed in the
      distances of the outer Co-Co bonds and Co-N (supporting ligand) bonds, which was
      consistent with the MO analysis. Electrochemical studies on both and showed one
      reversible oxidation and one reversible reduction at E(1/2) = +0.82 and -0.05 V
      for , and at E(1/2) = +0.89 and +0.02 V for , respectively. The redox reactions
      of the thiocyanate complex happened at higher potentials than the chloride
      complex . A magnetism study of revealed anomalous magnetic behaviour similar to
      that of heptacobalt EMACs, and a deviation from the Curie-Weiss law was observed.
      The chi(M)T value at 300 K is 0.84 and 1.16 emu K mol(-1) for and , respectively,
      suggesting spin-equilibrium or a spin-admixture between doublet and quartet
      states arising from the Boltzmann distribution over different energy levels.
      Similar results were obtained for and , showing intermediate chi(M)T values
      between a diamagnetic and a triplet state of 0.15-0.96 emu K mol(-1) in the
      temperature range 5-300 K. The structural and magnetic results were interpreted
      through an EHMO study.

PMID- 19153627
TI  - d(10)-Metal coordination polymers based on analogue di(pyridyl)imidazole
      derivatives and 4,4'-oxydibenzoic acid: influence of flexible and angular
      characters of neutral ligands on structural diversity.
AB  - A series of mixed-ligand coordination complexes, namely [Zn(L(1))(oba)] (),
      [Cd(L(1))(oba)] (), [Zn(2)(L(2))(oba)(2)].8H(2)O (), [Cd(2)(L(2))(oba)(2)].2H(2)O
      (), [Zn(3)(L(3))(oba)(3)] (), [Cd(2)(L(3))(oba)(2)].(L(3)) (),
      [Cd(L(4))(oba)].H(2)O () and [Cd(L(5))(oba)].3H(2)O (), where L(1) = 2-(2
      pyridyl)imidazole, L(2) = 1,4-bis[2-(2-pyridyl)imidazol-1-yl]butane, L(3) = 1,4
      bis[2-(2-pyridyl)imidazol-1-ylmethyl]benzene, L(4) = 1,3-bis[2-(2
      pyridyl)imidazol-1-ylmethyl]benzene, L(5) = 1,2-bis[2-(2-pyridyl)imidazol-1
      ylmethyl]benzene and H(2)oba = 4,4'-oxydibenzoic acid, have been synthesized
      under hydrothermal conditions. Their structures have been determined by single
      crystal X-ray diffraction analyses and further characterized by elemental
      analyses, IR spectra, and thermogravimetric (TG) analyses. In compounds and ,
      oba(2-), L(1) ligand and Zn(II) or Cd(II) ions assemble to form the parallel
      chains or parallel sheets which are linked by the weak hydrogen bonding and pipi
      stacking interactions to give the 2D supramolecular sheet or 3D supramolecular
      net, respectively. For , L(2) ligands connect [Zn(oba)] chains to generate a
      unusual (10,3)-b topological structure which is the first example for eight-fold
      interpenetrating framework based on the (10,3)-b net. In , L(2) ligands link
      [Cd(oba)] double-chains to give a 2D sheet which is assembled by pipi stacking
      interactions to obtain a 3D supramolecular net. In , L(3) ligands link Zn(II)
      ions from alpha-Po net formed by Zn(II) ions and oba(2-) anions to show a novel
      3D 8-connected self-penetrating framework with the unreported (4(16).6(11).8)
      topological structure. In , the double-chains constructed by Cd(II) and oba(2-)
      anions are linked by one kind of L(3) ligand to form a layer-like structure which
      is assembled by pipi stacking interactions to show a 3D supramolecular structure.
      In , oba(2-) anions coordinate to Cd(II) cations to form chains which are
      connected by L(4) to form a four-fold interpenetrating diamond network. In , the
      weak hydrogen bonding and pipi stacking interactions connect the [Cd(L(5))(oba)]
      chains to give a 2D supramolecular sheet. By careful inspections of the
      structures of , we believe that the different flexible and angular neutral
      ligands, coordination geometries of metal centers and weak interactions (hydrogen
      bonds and pipi stacking interactions) are crucial factors for the formation of
      the different structures. The photoluminescent properties of have been studied in
      the solid state at room temperature.

PMID- 19153629
TI  - A flexible 1,8-naphthyridyl derivative and its Zn(II) complexes: synthesis,
      structures, spectroscopic properties and recognition of Cd(II).
AB  - A flexible ligand bis(7-methyl-1,8-naphthyridine-2-ylamino)methane (), having
      kappa(4)-chelating and kappa(2)-bridging modes, and its intriguing structural
      complexes of Zn(II) with mu-OH, kappa(1)-OAc, mu-kappa(1)-OAc and mu-kappa(2)-OAc
      ligands, [Zn(2)()(2)(OH)](ClO(4))(3) (), [Zn(4)()(2)(OAc)(6)(OH)(2)].CH(2)Cl(2)
      (.CH(2)Cl(2)) and [Zn(5)()(2)(OAc)(10)](n).4nH(2)O (.4H(2)O) were synthesized and
      their structures were determined by X-ray crystallography. These compounds
      exhibited intense blue fluorescent emissions with a lambda(max) in the range of
      380-410 nm in CH(2)Cl(2), CH(3)CN and CH(3)OH solutions, and solid-state
      emissions centered at 416, 463, 490 and 451 nm were observed for the compounds ,
      , and at room temperature, respectively. The investigated fluorescence properties
      of associated with various metal ions showed that the fluorescence enhancement of
      with Cd(II) was more sensitive than with other interfering cations.

PMID- 19153630
TI  - In search of molecular precursors for cadmium sulfide-new complexes with a sulfur
      rich kernel: cadmium(ii) tri-tert-butoxysilanethiolates with additional
      diethyldithiocarbamato ligand.
AB  - The reaction of dimeric bis(tri-tert-butoxysilanethiolato)cadmium(ii)
      [Cd{SSi(OBu(t))(3)}(2)](2) with diethyldithiocarbamate sodium salt in the
      presence of quaternary ammonium salts resulted in formation of three new
      heteroleptic cadmium(ii) complexes-the first silanethiolate species possessing
      additionally other S-donor ligands. Neutral as well as ionic compounds and can be
      obtained with a good yield depending on the quaternary salt and solvent used.
      Their X-ray structures have been determined-complex
      [Cd{SSi(OBu(t))(3)}(S(2)CNEt(2))](2) turned out to be dimeric in the solid state,
      while and are monometallic species with a [Cd{SSi(OBu(t))(3)}(2)(S(2)CNEt(2))](-)
      anion. The cadmium atom in each case has been found tetra-coordinated with a
      distorted CdS(4) kernel. Elemental and spectral analyses (IR, NMR, UV-vis) were
      carried out. Thin films of and prepared on SiO(2) substrates via spin coating
      technique were analysed by AFM and XPS. The thermal decomposition product of was
      analysed using XRD, EDS, SEM and TEM measurements and identified as hexagonal
      CdS.

PMID- 19153631
TI  - Organo-aluminium and -gallium complexes with omega-NH-functional alkoxide
      ligands.
AB  - The aminoalcohols MeNH(CH(2))(2)OH (), (t)BuNH(CH(2))(2)OH (), MeNH(CH(2))(3)OH
      (), (t)BuNH(CH(2))(3)OH () and MeNHCH(2)CMe(2)CH(2)OAlMe(2) () have been reacted
      with AlMe(3) to give the five corresponding aminoalkoxides of the general formula
      RNH-X-AlMe(2)- (X = organic spacer between N and O). (t)BuNHCH(2)CMe(2)CH(2)OH ()
      reacts with AlMe(3) to give [(t)BuNHCH(2)CMe(2)CH(2)OAlMe(2)].AlMe(3) (.AlMe(3)).
      Analogous reactions of the aminoalcohols , , and with Al(t)Bu(3), GaMe(3) and
      Ga(t)Bu(3) afforded the corresponding aminoalkoxides of the general formula RNH-X
      MR'(2)- (MR'(2) = Al(t)Bu(2)), - (MR'(2) = GaMe(2)) and - (MR'(2) = Ga(t)Bu(2)).
      The compounds were characterised by NMR spectroscopy, elemental analyses and mass
      spectrometry. Crystal structures were determined for , , .AlMe(3), , , and .
      Compounds and dimerise via Al(2)O(2) rings, while the amino-functions form
      intramolecular Al-N bonds. Compounds and form monomers with intramolecular Ga-N
      bonds. Compounds and are dimers via Ga(2)O(2) rings but in contrast to and
      without formation of intramolecular Ga-N bonds. .AlMe(3) also forms a monomeric
      compound with intramolecular AlN bond and a further AlMe(3) unit bonded to the O
      atom. The dynamic behaviour of and was investigated by variable-temperature NMR
      spectroscopy. Some compounds have different aggregation in solid and fluid
      phases.

PMID- 19153632
TI  - Unexpected effect of the ring on the extent of Si...H interligand interactions in
      half-sandwich silyl hydrides of ruthenium.
AB  - This paper reports preparation of new silyl hydride complexes of ruthenium
      supported by the Cp/PR(3) ligand set. It is shown that the easiest and most
      general route to these complexes is provided by the thermal reaction of
      [RuCp(PR(3))(H)(3)] with hydrosilanes. Complexes [RuCp(PR(3))(H)(2)(SiMe(2)Cl)]
      exhibit Interligand Hypervalent Interactions (IHI) between the hydride and silyl
      ligands. Comparison of the X-ray structures of complexes
      [RuCp(PPr(i)(3))(H)(2)(SiMe(2)Cl)], [RuCp(PPhPr(i)(2))(H)(2)(SiMe(2)Cl)], and
      [RuCp(PPh(3))(H)(2)(SiMe(2)Cl)] shows that the IHI weakens with the decreasing
      electron-releasing ability of the phosphine. Comparison of the X-ray structure of
      [RuCp(PPh(3))(H)(2)(SiMe(2)Cl)] with the structure of the previously reported
      complex [RuCp*(PPh(3))(H)(2)(SiMe(2)Cl)] reveals that the lack of IHI in the
      latter compound is due to unfavourable steric interactions between the bulkier
      Cp* ring and the SiMe(2)Cl group.

PMID- 19153633
TI  - Genome-based expression profiles as a single standardized microarray platform for
      the diagnosis of experimental interstitial cystitis: an array of 75 genes model.
AB  - INTRODUCTION AND HYPOTHESIS: To investigate the molecular signature underlying
      experimental interstitial cystitis (IC) using cDNA microarray. METHODS:
      Microarray gene expression profiles are studied in bladder epithelium of C57BL/6
      mice with ovalbumin or substance P-induced experimental IC versus Escherichia
      coli lipopolysaccharide-induced bacterial cystitis. RESULTS: Main findings are
      summarized as follows: firstly, a "75-gene" model was discovered to contain high
      expressions of bladder epithelium which feature in experimental IC. Secondly,
      glucose, lipid, nucleotide, xenobiotics, and amino acid metabolisms are involved
      in. Thirdly, T-cell-mediated immune and inflammatory responses are observed.
      Fourthly, Wnt, Tgf-beta, Mapk, and insulin growth factor receptor signaling
      pathways are also involved in. In addition, experimental IC leads to Ephrin- and
      Semaphorin-mediated axon guidance promoting parasympathetic inflammatory
      reflexes. CONCLUSIONS: Further characterization of human IC-induced gene
      expression profiles would enable the use of genome-based expression profiling for
      the therapeutic targets and diagnosis of IC.

PMID- 19153634
TI  - Differential drug responses on native GABA(A) receptors revealing heterogeneity
      in extrasynaptic populations in cultured hippocampal neurons.
AB  - Hippocampal pyramidal neurons potentially express multiple subtypes of GABA(A)
      receptors at extrasynaptic locations that could therefore respond to different
      drugs. We activated extrasynaptic GABA(A) receptors in cultured rat hippocampal
      pyramidal neurons and measured single-channel currents in order to compare the
      actions of two drugs that potentially target different GABA(A) receptor subtypes.
      Despite the possible difference in receptor targets of etomidate and diazepam,
      the two drugs were similar in their actions on native extrasynaptic GABA(A)
      receptors. Each drug produced three distinct responses that differed
      significantly in current magnitude, implying heterogeneous GABA(A) receptor
      populations. In the majority of patches, drug application increased both the
      single-channel conductance (>40 pS) and the open probability of the channels. By
      contrast, in the minority of patches, drug application caused an increase in open
      probability only. In the third group high-conductance channels were observed upon
      GABA activation and drug application increased their open probability only. The
      currents potentiated by etomidate or diazepam were substantially larger in
      patches displaying high-conductance GABA channels compared to those displaying
      only low-conductance channels. Factors contributing to the large magnitude of
      these currents were the long mean open time of high-conductance channels and the
      presence of multiple channels in these patches. In conclusion, we suggest that
      the local density of extrasynaptic GABA(A) receptors may influence their single
      channel properties and may be an additional regulating factor for tonic
      inhibition and, importantly, differential drug modulation.

PMID- 19153635
TI  - Bladder dysfunction in subacute combined degeneration: a clinical, MRI and
      urodynamic study.
AB  - OBJECTIVE: In view of the paucity of studies on micturition disturbance in
      subacute combined degeneration (SACD), this prospective study reports micturition
      disturbance in SACD and correlations with urodynamic and MRI findings. METHODS:
      SACD was diagnosed by clinical features and low serum B12 level (< 211 pg/ml)
      and/or megaloblastic bone marrow. Micturition disturbances were categorized into
      voiding and storage symptoms and scored using the American Urological Association
      Symptoms (AUAS) score. Spinal MRI and urodynamic studies were carried out.
      Patients were treated with vitamin B12 1000 microg daily i.m. and outcome was
      defined at 6 months into complete, partial and poor. RESULTS: Eight patients with
      SACD aged 53.8 (44-70) years were included; 2 of whom were females. The mean
      duration of illness was 2.2 (1-120) months. All had walking difficulty, 2 were
      wheelchair bound and 4 bedridden. Lower limb spasticity and joint position
      impairment were present in all; ankle reflex was absent and pinprick sensation
      reduced distally in 4 patients each. T2 hyperintensity in the posterior spinal
      cord was present in 5 and in subcortical white matter in 2 patients. Five
      patients had storage, 7 voiding and 4 had both dysfunctions. AUAS score was 14.63
      (4-35). On urodynamic study, detrusor areflexia was present in 2, neurogenic
      detrusor overactivity with high pressure voiding in 3 and normal in 2 patients.
      The urinary symptoms improved in all (AUAS score 3.67). Repeat urodynamic study
      in 2 patients, who had detrusor areflexia improved. At 6 mo, 3 patients had
      complete, 4 partial and 1 poor recovery. CONCLUSION: Bladder symptoms occur in
      advanced cases of SACD; both detrusor areflexia and neurogenic detrusor
      overactivity with high pressure voiding occur and respond to B12 therapy.

PMID- 19153636
TI  - Klebsiella meningoencephalitis presenting like embolic ischemic stroke.

PMID- 19153638
TI  - Homozygosity for a NOTCH3 mutation in a 65-year-old CADASIL patient with mild
      symptoms: a family report.

PMID- 19153637
TI  - Impaired performance on the Wisconsin Card Sorting Test under left- when compared
      to right-sided deep brain stimulation of the subthalamic nucleus in patients with
      Parkinson's disease.
AB  - Over the past decade, deep brain stimulation (DBS) has become an effective
      treatment option for managing severe Parkinson's disease (PD). However, evidence
      is accumulating that DBS of target sites like the subthalamic nucleus (STN) can
      result in unintended cognitive effects that lie beyond motor control. The aim of
      the present study was to evaluate whether changes in executive task performance
      after chronic DBS might be predominantly associated with the stimulation of only
      one hemisphere. Eight patients with PD who had undergone DBS treatment of the STN
      were selected to participate in the study. Using a repeated measurements design,
      they underwent a neuropsychological examination under unilateral left- and right
      sided stimulation in order to investigate laterality effects in their performance
      on the Wisconsin Card Sorting Test. All patients showed a significant improvement
      in motor symptoms postoperatively. Selected aspects of executive task performance
      were compromised under left- when compared to right-sided stimulation.
      Performance measures were unrelated to demographic, neurological, and behavioral
      characteristics of the patients. Findings are consistent with the emerging
      evidence that the STN is not only involved in motor control, but also
      participates in functions of the cognitive domain. Moreover, results raise the
      possibility that the left and right hemisphere might differ in their
      vulnerability to tolerate side effects on executive functions of DBS treatment.
      Potential consequences for future research questions and the management of
      cognitive side effects are discussed.

PMID- 19153639
TI  - Molecular evolution of human influenza A viruses in a local area during eight
      influenza epidemics from 2000 to 2007.
AB  - A total of 1,041 human influenza A virus isolates were collected at a clinic in
      Niigata, Japan, during eight influenza seasons from 2000 to 2007. The H3N2
      subtype accounted for 75.4% of the isolates, and the rest were H1N1. Extremely
      high rates of amantadine-resistant strains of H3N2 subtype were observed in
      2005/2006 (100%) and 2006/2007 (79.4%), while amantadine-resistant strains of
      H1N1 subtype were only detected in 2006/2007 (48.2%). Sequence and phylogenetic
      analysis of the HA1 subunit of the hemagglutinin (HA) gene revealed a
      characteristic linear trunk in the case of H3N2 viruses and a multi-furcated tree
      in the case of H1N1 and showed a higher sequence diversity among H3N2 strains
      than H1N1 strains. Mutations in the HA1 from both subtypes were mainly found in
      the globular region, and only one-third of these were retained for two or more
      successive years. Higher diversity of H3N2 viruses was mainly attributable to a
      higher fixation rate of non-synonymous mutations and to a lesser extent to a
      higher nucleotide substitution rate than for H1N1. Our analysis showed evidence
      of four positively selected sites in the HA1 of H1 and five sites in that of H3,
      four of which were novel. Finally, acquisition or loss of N-glycosylation sites
      was shown to contribute to the evolution of influenza A virus, especially in the
      case of H3N2, which had a higher tendency to acquire new glycosylation sites.

PMID- 19153640
TI  - Relationship between U83 gene variation in human herpesvirus 6 and secretion of
      the U83 gene product.
AB  - The betaherpesvirus human herpesvirus 6 (HHV-6) has two variants. The U83 gene
      product of strain HST is a chemoattractant for monocytes. Here, we describe U83
      gene variations that accumulated in variants A and B. A gene-variation hot spot
      was examined in 36 different strains and one donor DNA sample. U83 gene
      variations accumulated in variant A and in reactivated variant B after
      transplantation. None of the variant-A viruses encoded the signal peptide found
      in the B variant. U83 gene sequencing suggested that the variant A and B groups
      were separate, and that the variant B viruses could be further divided into the
      HST-Z29 type and another type with a shorter signal peptide. In a eukaryotic
      expression system, the HST-Z29 type of U83 gene product was secreted into the
      medium, a frame-shifted HST-Z29 type was partially secreted, and the variant-A
      type and a first-methionine knockout of the HST-Z29 type were not secreted.

PMID- 19153641
TI  - Genome segment reassortment identifies non-structural protein NS3 as a key
      protein in African horsesickness virus release and alteration of membrane
      permeability.
AB  - The role of African horsesickness virus (AHSV) nonstructural membrane protein NS3
      in determining the effects of AHSV infection on Vero cells was examined. NS3
      protein sequences are highly variable and cluster into three phylogenetic groups,
      alpha, beta, and gamma. Three AHSV strains, with NS3 from alpha, beta, or gamma,
      were shown to have quantitatively different phenotypes in Vero cells.
      Reassortants between these strains, in which the S10 genome segment encoding NS3
      was exchanged alone or with other segments, were generated and compared to
      parental strains. Exchange of the NS3 gene resulted in changes in virus release,
      membrane permeability and total virus yield, indicating an important role for NS3
      in these viral properties. Differences in the cytopathicity and the effect on
      cell viability between the parental strains could not be associated with NS3
      alone, and it is likely that a number of viral and host factors play a role.

PMID- 19153642
TI  - D-Aspartate binding sites in rat Harderian gland.
AB  - Radioligand binding of D-[(3)H]aspartic and L-[(3)H]glutamic acids to plasma
      membranes from rat Harderian gland was evaluated. Binding was optimal under
      physiological conditions of pH and temperature, and equilibrium was reached
      within 50 min. Specific binding for D-Asp and L-Glu was saturable, and Eadie
      Hofstee analysis revealed interaction with a single population of binding sites
      (for D-Asp K(d) = 860 +/- 28 nM, B(max) = 27.2 +/- 0.5 pmol/mg protein; for L
      Glu, K(d) = 580 +/- 15 nM and B(max) = 51.3 +/- 0.8 pmol/mg protein). L
      [(3)H]glutamate had higher affinity and a greater percentage of specific binding
      than did D-[(3)H]aspartate. The pharmacological binding specificity of L
      [(3)H]glutamate indicated an interaction with NMDA-type receptors. Specifically,
      the order of potency of the displacing compound tested was L-Glu > D-Asp > NMDA >
      MK801 > D-AP5 > glycine. For D-[(3)H]aspartate, the data revealed an interaction
      of D: -Asp with either NMDA-type receptors or putative specific binding sites.

PMID- 19153643
TI  - Microscopic hematuria is associated with low bone mineral density in aged women
      and men.
AB  - Little is known concerning renal or urological risk factors for osteoporosis. The
      aim of this study was to explore an association between urinalysis and bone
      mineral density (BMD) in 4,835 Japanese adults. Participants were 4,835
      individuals (female 3,683; male 1,152) aged 50 years and over who received a
      health check-up between January 1995 and March 2006 in Japan. BMD of the distal
      radius and ulna of the non-dominant forearm was measured by the dual-energy X-ray
      absorptiometry (DXA) method using a DTX-200 Dexacare osteometer (Osteometer
      MediTech A/S, Rodovre, Denmark). Urine variables were protein, and red blood
      cells (RBCs) and white blood cells (WBCs) in urine sediment (categorized as <1, 1
      4, 5-9, or >or=10 cells per high-power microscopic field). Average age was 58.9
      years (SD 5.6) in women, and 60.5 years (SD 6.2) in men. Simple linear regression
      analysis showed that urinary RBCs were associated with BMD in women (beta = or
      5.88 x 10(-3), R (2) = 0.004, p < 0.0001) and men (beta = or-1.34 x 10(-2), R (2)
      = 0.013, p = 0.0001). These associations held when possible confounders were
      adjusted (beta = or-2.05 x 10(-3), R (2) = 0.001, p = 0.0338 for women and beta
      =or -5.67 x 10(-3), R (2) = 0.006, p = 0.0163 for men). Microscopic hematuria is
      associated with forearm BMD in women and men aged 50 years and over. Further
      studies should be conducted to determine the mechanisms underlying this
      association.

PMID- 19153644
TI  - Delayed repair for traumatic abdominal wall hernia: is it safe?
AB  - Abdominal wall hernias after trauma have been recognized for more than a century,
      with the first case reported as occurring after a fall. Traumatic abdominal wall
      hernias (TAWHs) after blunt trauma are uncommon. The timing of definitive repair,
      early or delayed, is not clear. We report a case on TAWH and mesenteric avulsion,
      highlighting the reasons for immediate or delayed repair. A single case study can
      hardly be considered as a basis for profound changes in the management of post
      traumatic hernias. However, damage to all layers of the abdominal wall indicates
      high-energy trauma. In such cases, the damage is not, in all probability, limited
      to the integumentary system. For the moment, the timing of surgery in any TAWH
      should be considered differently according to the trauma, the wall defect,
      clinical and radiological findings, associated injuries, and the clinical status
      of the patient.

PMID- 19153645
TI  - Incarcerated hernia: to reduce or not to reduce?
AB  - PURPOSE: Before the advent of general anesthesia, taxis (hernia reduction) was
      the treatment of choice of incarcerated hernia but, over the years, its use
      subsided in favor of urgent herniorrhaphy. The role of taxis for incarcerated
      hernias in a growing geriatric population must be reexamined. METHODS: We
      attempted taxis in 101 adult patients diagnosed with anterior abdominal wall
      incarcerated hernia. Following successful taxis, patients were hospitalized for a
      24-h period of observation to obviate any complications of taxis. Upon their
      discharge, the patients were advised to follow with an elective hernia repair.
      Unsuccessful attempts at taxis were followed by emergency surgery. The gender of
      the patient, type of hernia, time lapse since incarceration, and signs of
      intestinal occlusion were recorded and mortality and morbidity rates were
      calculated. RESULTS: Taxis was successful in 60.3% of cases. No taxis-related
      complication was observed, even though the mean delay in presentation since
      incarceration was 12 h. Mortality and morbidity within the taxis group were null.
      CONCLUSION: Taxis is a feasible and safe maneuver pending an eventual surgical
      treatment. By offering better conditions at a later repair, the mortality and
      morbidity may be considerably lowered. Further studies are needed in order to
      elucidate various aspects of this two-stage treatment of incarcerated hernia.

PMID- 19153646
TI  - Three-year follow-up of modified Lichtenstein inguinal hernioplasty using
      lightweight poliglecaprone/polypropylene mesh.
AB  - BACKGROUND: This prospective cohort study evaluated whether partially absorbable
      monofilament mesh could influence postoperative pain and time of the return to
      normal activity while not increasing recurrence in modified Lichtenstein inguinal
      hernioplasty. METHODS: Two hundred and forty-two patients were operated on using
      poliglecaprone/polypropylene mesh. A modified Lichtenstein technique was used
      (more stitches and larger margin of mesh on the inguinal ligament, additional
      suture near the pubic bone). Follow-up data were collected at 3 years. The
      objective was to assess the incidence of late persistent postoperative pain and
      the recurrence rate. RESULTS: The follow-up rate reached 88.37%. The recurrence
      rate was 2.2% (four patients). All recurrences appeared within the first 12
      months. Slight discomfort, feelings of stiffness, and the occasional appearance
      of foreign bodies that did not influence daily activity were noted in 20 patients
      (10.8%). Chronic pain was found in 22 patients (11.1%), but only affected the
      daily activities of seven (3.24%). Only one patient suffering from pain described
      it as stronger than before the operation. CONCLUSIONS: The use of partially
      absorbable light mesh reduces postoperative pain at long-term follow-up. The
      recurrence rate was not increased at 36 months follow-up.

PMID- 19153647
TI  - Italian multicentre study of peroneal mononeuropathy: multiperspective follow-up.
AB  - The main objective of this study is to assess the course of peroneal
      mononeuropathy (PM). The study design includes Clinical and Prospective study.
      The setting involves neurophysiological Service. From November 2002 to January
      2004, we enroled 69 consecutive patients and prospectively followed up 49
      patients with multiple measurements. Comparison was made between follow-up and
      baseline values, and baseline factors were used to predict the PM evolution in
      multiple regression analysis. At follow-up, we observed a significant improvement
      of all clinical, neurophysiological and disability measurements, and physical
      aspects of quality of life (QoL). Greater muscle strength of tibialis anterior
      and higher conduction velocity of peroneal nerve at baseline were seen to be
      positive prognostic factors. A better evolution of mental aspects of QoL was
      observed in the subacute group and in younger patients, while a better physical
      evolution in QoL was observed in women. Rehabilitation is ambiguously associated
      with a better Deambulation Index but lower ratings in mental aspects of QoL. In
      conclusion, PM shows a positive spontaneous course and rehabilitation seems to
      help the recovery of deambulation. Further studies on the effects of conventional
      rehabilitation are needed.

PMID- 19153648
TI  - Coping strategies, psychological variables and their relationship with quality of
      life in multiple sclerosis.
AB  - The aim of this study was to assess the impact of psychological features in the
      choice of coping strategies in multiple sclerosis (MS) patients, and their
      influence on quality of life (QoL). One hundred four patients (72 women, age 45.3
      +/- 10.9 years, disease duration 17.9 +/- 13.2 years, Expanded Disability Status
      Scale 2.8 +/- 2.0) were assessed through the Beck Depression Inventory, the State
      Trait Anxiety Inventory, the Eysenck Personality Questionnaire, the Coping
      Orientation for Problem Experiences-New Italian version and the MSQoL-54. MS
      patients were less likely to use problem-focused strategies, whereas avoiding
      strategies were adopted more frequently. The use of positive strategies
      positively influenced both mental and overall QoL. Depression had a negative
      impact on all QoL domains and anxiety on mental domains. These data point out the
      importance of a comprehensive assessment of MS patients. Orienting therapeutic
      interventions, to oppose depression and anxiety and to favour more appropriate
      coping strategies can improve the patients' QoL.

PMID- 19153650
TI  - Jactatio extra-capitis and migraine suppression.
AB  - Sleep often terminates migraine headaches, and sleep disorders occur with greater
      prevalence in individuals with chronic or recurrent headaches. Rhythmic head,
      limb or body movements are common in children before falling asleep, but they
      very rarely persist into adolescence and adulthood, or appear de novo later in
      life as sleep-related rhythmic movement disorders. A 22-year-old female with
      migraine without aura and history of early childhood pre-dormital body rocking
      (jactatio) discovered that unilateral slow rhythmic movements of her right foot
      greatly facilitated falling sound asleep while reclining. Sleep served every time
      to terminate her migraine attack. Rhythmic movements may serve on occasion as a
      therapeutic hypnotic maneuver in migraine sufferers.

PMID- 19153649
TI  - The assessment of beta amyloid, tau protein and cystatin C in the cerebrospinal
      fluid: laboratory markers of neurodegenerative diseases.
AB  - To assess the role of tau protein, beta-amyloid(1-42) and cystatin C in the
      diagnostics of Alzheimer dementia (AD) and other neurodegenerative diseases (ND)
      by comparing to the control groups (CG). The levels of tau protein, beta
      amyloid(1-42) and cystatin C were assessed in the set of 69 patients (AD + ND, 33
      males, 36 females, aged 22-90, mean 60.5 + 16.1 years), and in a control group of
      69 subjects without the affection of the central nervous system (CGAD + CGND, 33
      males, 36 females, aged 20-91, mean 60.5 + 16.0 years). Statistically significant
      increased tau protein levels (P = 0.0001) and index tau/beta-amyloid(1-42) levels
      (P = 0.0002) were shown in the group of AD patients, compared to the group of ND
      patients. One-way ANOVA analysis with Bonferonni post hoc test did not show any
      significant differences of the cystatin C values between any of the compared
      groups. ROC analysis showed at least one tie between the positive actual state
      group (AD) and the negative actual state group (ND) by CSF cystatin C and at
      least one tie between the positive actual state group and the negative actual
      state group by CSF tau protein. Our study confirmed previously reported results
      only in part. While tau protein seems to be quite a reliable marker of AD, the
      role of beta-amyloid(1-42) and cystatin C in AD diagnosis remains at least
      questionable.

PMID- 19153651
TI  - Apolipoprotein M affecting lipid metabolism or just catching a ride with
      lipoproteins in the circulation?
AB  - Apolipoprotein M (apoM) is a novel apolipoprotein found mainly in high-density
      lipoproteins (HDL). Its function is yet to be defined. ApoM (25 kDa) has a
      typical lipocalin ss-barrel fold and a hydrophobic pocket. Retinoids bind apoM
      but with low affinity and may not be the natural ligands. ApoM retains its signal
      peptide, which serves as a hydrophobic anchor to the lipoproteins. This prevents
      apoM from being lost in the urine. Approximately 5% of HDL carries an apoM
      molecule. ApoM in plasma (1 microM) correlates strongly with both low-density
      lipoprotein (LDL) and HDL cholesterol, suggesting a link to cholesterol
      metabolism. However, in casecontrol studies, apoM levels in patients with
      coronary heart disease (CHD) and controls were similar, suggesting apoM levels
      not to affect the risk for CHD in humans. Experiments in transgenic mice
      suggested apoM to have antiatherogenic properties; possible mechanisms include
      increased formation of pre-ss HDL, enhanced cholesterol mobilization from foam
      cells, and increased antioxidant properties.

PMID- 19153652
TI  - Bitter peptides and bitter taste receptors.
AB  - Bitter peptides are a structurally diverse group of oligopeptides often generated
      in fermented, aged, and hydrolyzed food products that make them unfavorable for
      consumption. Humans perceive bitterness by a repertoire of 25 human bitter
      receptors, termed T2Rs. Knowledge of the structural features of bitter receptors
      and of the factors that stimulate bitter receptors will aid in understanding the
      mechanism responsible for bitter taste perception. This article reviews the
      current knowledge regarding structural features of bitter peptides and bitter
      taste receptors.

PMID- 19153653
TI  - The role of microRNAs in metastasis and epithelial-mesenchymal transition.
AB  - For a tumour cell to metastasize it must successfully negotiate a number of
      events, requiring a series of coordinated changes in the expression of many
      genes. MicroRNAs are small non-coding RNA molecules that post-transcriptionally
      control gene expression. As microRNAs are now recognised as master regulators of
      gene networks and play important roles in tumourigenesis, it is no surprise that
      microRNAs have recently been demonstrated to have central roles during
      metastasis. Recent work has also demonstrated critical roles for microRNAs in
      epithelial-mesenchymal transition, a phenotypic change underlain by altered gene
      expression patterns that is believed to mirror events in metastatic progression.
      These findings offer new potential for improved prognostics through expression
      profiling and may represent novel molecular treatment targets for future therapy.
      In this review, we summarise the multistep processes of metastasis and epithelial
      mesenchymal transition and describe the recent discoveries of microRNAs that
      participate in controlling these processes.

PMID- 19153654
TI  - DNA repair in mammalian cells: DNA double-strand break repair: how to fix a
      broken relationship.
AB  - DNA double-strand breaks (DSBs) arise in cells from endogenous and exogenous
      attacks on the DNA backbone, but also as a direct consequence of replication
      failures. Proper repair of all these DSBs is essential for genome stability.
      Repair of broken chromosomes is a challenge for dividing cells that need to
      distribute equal genetic information to daughter cells. Consequently, eukaryotic
      organisms have evolved multi-potent and efficient mechanisms to repair DSBs that
      are primarily divided into two types of pathways: nonhomologous end joining
      (NHEJ) and homologous recombination (HR). Here we briefly describe how eukaryotic
      cells sense DSBs and trigger cell cycle arrest to allow repair, and we review the
      mechanisms of both NHEJ and HR pathways and the choice between them. (Part of a
      Multi-author Review).

PMID- 19153655
TI  - DNA Repair in mammalian cells: Mismatched repair: variations on a theme.
AB  - Complementary base pairing underlies the genetic template function of the DNA
      double helix. Therefore, to assure faithful DNA transactions, cells must adhere
      to a strict application of the Watson-Crick base pairing principle.Yet,
      mispairing does arise in DNA, most frequently as a result of DNA polymerase
      errors or base damage. These mismatches need be rectified to avoid mutation.
      Sometimes, however, mispairing is actively induced to trigger mutagenesis. This
      happens in activated B-lymphocytes, where the targeted generation and processing
      of G.U mismatches contributes to somatic hypermutation and antibody
      diversification. Non-mutagenic mismatches arise in heteroduplex intermediates of
      homologous recombination, and their processing helps restrict homeologous
      recombination. Depending on the type of mismatch and the biological context of
      its occurrence, cells must apply appropriate strategies of repair to properly
      control mutagenesis. This review will illustrate conceptual and functional
      challenges of cellular mismatch correction on typical examples of mutagenic base
      base mismatches. (Part of a Multi-author Review).

PMID- 19153656
TI  - DNA repair in mammalian cells: Transcription-coupled DNA repair: directing your
      effort where it's most needed.
AB  - Arrest of transcription at sites of DNA damage represents a strong signal for
      apoptosis. To overcome the impasse represented by transcription complexes
      arrested at sites of damage, cells have evolved a specialized nucleotide excision
      repair (NER) pathway called transcription-coupled DNA repair (TCR), dedicated to
      removal of transcription-blocking lesions from the genome. This repair pathway
      was discovered in Phil Hanawalt's laboratory 20 years ago, but the mechanistic
      details are still subject of intense research. This article will review the
      recent literature on the subject with emphasis on how lesions affect the
      elongation step of transcription and how the initial steps of TCR occur in human
      cells. (Part of a Multi-author Review).

PMID- 19153657
TI  - DNA repair in mammalian cells : Nucleotide excision repair: variations on
      versatility.
AB  - Nucleotide excision repair (NER) is one of the most versatile DNA repair systems.
      It can be subdivided into several, differentially regulated, subpathways: global
      genome repair (GGR), transcription-coupled repair (TCR), and transcription domain
      associated repair (DAR). This review begins with a brief overview of the numerous
      types of DNA lesions handled by NER, and proceeds to describe in detail the
      molecular mechanisms of NER. It then addresses heterogeneities in NER activity in
      physiological situations (e. g. in differentiated cells) and explores the
      underlying regulatory mechanism. It then reviews several inherited diseases
      associated with NER deficiencies: xeroderma pigmentosum, Cockayne syndrome,
      trichothiodystrophy, UV-sensitive syndrome. It concludes by discussing several
      currently unresolved issues, relating either to the cause of the above diseases
      or to the mechanistic details of the various NER subpathways and of their
      regulation. (Part of a Multi-author Review).

PMID- 19153658
TI  - DNA repair in mammalian cells: Base excision repair: the long and short of it.
AB  - Base excision repair (BER) is the primary DNA repair pathway that corrects base
      lesions that arise due to oxidative, alkylation, deamination, and
      depurinatiation/depyrimidination damage. BER facilitates the repair of damaged
      DNA via two general pathways - short-patch and long-patch. The shortpatch BER
      pathway leads to a repair tract of a single nucleotide. Alternatively, the long
      patch BER pathway produces a repair tract of at least two nucleotides. The BER
      pathway is initiated by one of many DNA glycosylases, which recognize and
      catalyze the removal of damaged bases. The completion of the BER pathway is
      accomplished by the coordinated action of at least three additional enzymes.
      These downstream enzymes carry out strand incision, gap-filling and ligation. The
      high degree of BER conservation between E. coli and mammals has lead to advances
      in our understanding of mammalian BER. This review will provide a general
      overview of the mammalian BER pathway. (Part of a Multi-author Review).

PMID- 19153659
TI  - DNA repair in mammalian cells: Direct DNA damage reversal: elegant solutions for
      nasty problems.
AB  - The genomic integrity of all living organisms is constantly jeopardized by
      physical [e.g. ultraviolet (UV) light, ionizing radiation] and chemical (e.g.
      environmental pollutants, endogenously produced reactive metabolites) agents that
      damage the DNA. To overcome the deleterious effects of DNA lesions, nature
      evolved a number of complex multi-protein repair processes with broad, partially
      overlapping substrate specificity. In marked contrast, cells may use very simple
      repair systems, referred to as direct DNA damage reversal, that rely on a single
      protein, remove lesions in a basically error-free manner, show high substrate
      specificity, and do not involve incision of the sugar-phosphate backbone or base
      excision. This concise review deals with two types of direct DNA damage reversal:
      (i) the repair of alkylating damage by alkyltransferases and dioxygenases, and
      (ii) the repair of UV-induced damage by spore photoproduct lyases and
      photolyases. (Part of a Multi-author Review).

PMID- 19153660
TI  - DNA repair in mammalian cells: So DNA repair really is that important?

PMID- 19153661
TI  - Cellular mechanisms regulating human melanogenesis.
AB  - The major differentiated function of melanocytes is the synthesis of melanin, a
      pigmented heteropolymer that is synthesized in specialized cellular organelles
      termed melanosomes. Mature melanosomes are transferred to neighboring
      keratinocytes and are arranged in a supranuclear cap, protecting the DNA against
      incident ultraviolet light (UV) irradiation. The synthesis and distribution of
      melanin in the epidermis involves several steps: transcription of melanogenic
      proteins, melanosome biogenesis, sorting of melanogenic proteins into the
      melanosomes, transport of melanosomes to the tips of melanocyte dendrites and
      finally transfer into keratinocytes. These events are tightly regulated by a
      variety of paracrine and autocrine factors in response to endogenous and
      exogenous stimuli, principally UV irradiation.

PMID- 19153662
TI  - Regulation of mitochondrial aconitase by phosphorylation in diabetic rat heart.
AB  - Mitochondrial dysfunction and protein kinase C (PKC) activation are consistently
      found in diabetic cardiomyopathy but their relationship remains unclear. This
      study identified mitochondrial aconitase as a downstream target of PKC activation
      using immunoblotting and mass spectrometry, and then characterized
      phosphorylation-induced changes in its activity in hearts from type 1 diabetic
      rats. PKCbeta(2) co-immunoprecipitated with phosphorylated aconitase from
      mitochondria isolated from diabetic hearts. Augmented phosphorylation of
      mitochondrial aconitase in diabetic hearts was found to be associated with an
      increase in its reverse activity (isocitrate to aconitate), while the rate of the
      forward activity was unchanged. Similar results were obtained on phosphorylation
      of mitochondrial aconitase by PKCbeta(2) in vitro. These results demonstrate the
      regulation of mitochondrial aconitase activity by PKC-dependent phosphorylation.
      This may influence the activity of the tricarboxylic acid cycle, and contribute
      to impaired mitochondrial function and energy metabolism in diabetic hearts.

PMID- 19153663
TI  - Misregulated RNA Pol II C-terminal domain phosphorylation results in apoptosis.
AB  - Misregulation of the level of RNA polymerase II carboxyl-terminal domain (CTD)
      phosphatase, Fcp1, in Drosophila results in high level of caspase-mediated
      apoptosis. Apoptosis induction by Fcp1 misregulation requires the presence of
      Drosophila melanogaster (Dm)p53, but occurs without the transcriptional
      activation of Dmp53 proapoptotic targets rpr, ark, and hid. Overproduction of a
      transcription activation-defective mutant Dmp53 protein increases, while Dmp53
      null background decreases significantly the level of apoptosis in Fcp1
      misregulated animals. Generating the apoptotic signal does not require the
      function of the ATM and Rad3-related kinase (ATR), and no significant level of
      nucleo-cytoplasmic translocation of Dmp53 is detectable in cells expressing Fcp1
      at an abnormal level. Immunostaining of larval salivary gland polytene
      chromosomes with anti-Dmp53 antibodies indicates Dmp53 localization at several
      transcriptionally active chromosomal regions in wild-type cells, while in Fcp
      misregulated cells the association of Dmp53 with specific chromosomal sites is
      decreased.

PMID- 19153664
TI  - A complex of Shc and Ran-GTPase localises to the cell nucleus.
AB  - The three isoforms of the adaptor protein Shc play diverse roles in cell
      signalling. For example, the observation of p46 Shc in the nuclei of
      hepatocellular carcinoma cells suggests a function quite distinct from the better
      characterised cytoplasmic role. Ligands responsible for the transport of various
      Shc isoforms into organelles such as the nucleus have yet to be reported. To
      identify such ligands a far western approach was used to determine the p52 Shc
      interactome. The Ran-GTPase nuclear transport protein was identified and found to
      bind to p52 Shc in vitro with low micromolar affinity. Co-immunoprecipitation,
      pull down and fluorescence lifetime imaging microscopy experiments in stable
      cells confirmed cellular interaction and nuclear localisation. The nuclear
      transport factor protein NTF2, which functions in cohort with Ran, was shown to
      form a complex with both RAN and Shc, suggesting a mechanism for Shc entry into
      the nucleus as part of a tertiary complex.

PMID- 19153665
TI  - CD20-related signaling pathway is differently activated in normal and dystrophic
      circulating CD133(+) stem cells.
AB  - Among the heterogeneous population of circulating hematopoietic and endothelial
      progenitors, we identified a subpopulation of CD133(+) cells displaying myogenic
      properties. Unexpectedly, we observed the expression of the B-cell marker CD20 in
      blood-derived CD133(+) stem cells. The CD20 antigen plays a role in the
      modulation of intracellular calcium homeostasis through signaling pathways
      activation. Several observations suggest that an increase in intracellular
      calcium concentration ([Ca(2+)](i)) could be involved in the etiology of the
      Duchenne muscular dystrophy (DMD). Here, we show that a CD20-related signaling
      pathway able to induce an increase in [Ca(2+)](i) is differently activated after
      brain derived neurotrophic factor (BDNF) stimulation of normal and dystrophic
      blood-derived CD133(+) stem cells, supporting the assumption of a "CD20-related
      calcium impairment" affecting dystrophic cells. Presented findings represent the
      starting point toward the expansion of knowledge on pathways involved in the
      pathology of DMD and in the behavior of dystrophic blood-derived CD133(+) stem
      cells.

PMID- 19153667
TI  - Novel methods of genome shuffling in Saccharomyces cerevisiae.
AB  - Genome shuffling can improve complex phenotypes; however, there are several
      obstacles towards its broader applicability due to increased complexity of
      eukaryotic cells. Here, we describe novel, efficient and reliable methods for
      genome shuffling to increase ethanol production of Saccharomyces cerevisiae.
      Using yeast sexual and asexual reproduction by itself, mutant diploid cells were
      shuffled through highly efficient sporulation and adequate cross among the
      haploid cells, followed by selection on the special plates. The selected strain
      obtained after three round genome shuffling not only distinctly improved the
      resistance to ethanol, but also, increased ethanol yield by up to 13% compared
      with the control.

PMID- 19153666
TI  - A sperm GPI-anchored protein elicits sperm-cumulus cross-talk leading to the
      acrosome reaction.
AB  - The acrosome reaction has long been thought to be induced by the zona pellucida.
      Here we report the identification and function of a novel human sperm
      glycosylphosphatidylinositol (GPI)-anchored membrane protein, NYD-SP8. The
      release of the protein during sperm-egg interaction and its binding to the
      cumulus, the first layer of egg investment, elicits cross-talk between the
      gametes and produces calcium dependant release of progesterone, which lead to the
      acrosome reaction. An in vivo mouse model of NYD-SP8 immunization is also
      established showing a reduced fertility rate. Thus, contrary to accepted dogma,
      our study demonstrates for the first time that, prior to reaching the zona
      pellucida, sperm may release a surface protein that acts on the cumulus cells
      leading to the acrosome reaction, which may be important for determining the
      outcome of fertilization.

PMID- 19153668
TI  - Emerging role of nuclear protein 1 (NUPR1) in cancer biology.
AB  - NUPR1, or p8 or com1, was first identified from rat pancreas during acute
      pancreatitis and later as a gene whose expression was upregulated in metastatic
      breast cancer cells. NUPR1 is a molecule whose expression is upregulated in
      response to stress and is hence influenced by the host microenvironment. While
      NUPR1 has been implicated in several diseases, there is no singular biochemical
      pathway that can be attributed to its role in cancer. NUPR1 has been found to aid
      the establishment of metastasis and to play a key role in the progression of
      several malignancies including those of breast, thyroid, brain and pancreas.
      NUPR1 has been implicated in inducing chemoresistance in pancreatic and breast
      cancer cells, protecting them from apoptosis and making tumor cells genetically
      unstable. In prostate cancer, however, NUPR1 appears to have tumor suppressive
      activity. Understanding the mechanism of action of the multifaceted functions of
      NUPR1 may open up new dimensions towards creating novel therapies against cancer
      as well as other pathologies. This review draws on several published studies on
      NUPR1, mainly in cancer biology, and assesses NUPR1 from the perspective of its
      functional role in making cancer cells resistant to the action of conventional
      chemotherapeutic drugs.

PMID- 19153669
TI  - E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer.
AB  - The embryonic program 'epithelial-mesenchymal transition' (EMT) is activated
      during tumor invasion in disseminating cancer cells. Characteristic to these
      cells is a loss of E-cadherin expression, which can be mediated by EMT-inducing
      transcriptional repressors, e.g. ZEB1. Consequences of a loss of E-cadherin are
      an impairment of cell-cell adhesion, which allows detachment of cells, and
      nuclear localization of beta-catenin. In addition to an accumulation of cancer
      stem cells, nuclear beta-catenin induces a gene expression pattern favoring tumor
      invasion, and mounting evidence indicates multiple reciprocal interactions of E
      cadherin and beta-catenin with EMT-inducing transcriptional repressors to
      stabilize an invasive mesenchymal phenotype of epithelial tumor cells.

PMID- 19153670
TI  - The mitotic functions of integrin-linked kinase.
AB  - The cytoskeleton is composed of three major constituents: actin filaments,
      intermediate filaments and microtubules. These are vital for numerous normal
      cellular processes including cell spreading and migration, intracellular
      organelle transport, mechanical strength, mitosis and cytokinesis. Deregulation
      of cytoskeletal components can lead to cells developing several oncogenic
      phenotypes; for example increased migration and invasiveness, defects in cellular
      morphogenesis and genetic instabilities due to errors in mitosis and cytokinesis.
      Integrin-linked kinase (ILK) is a protein with well established roles in
      regulating actin cytoskeletal reorganization, survival, proliferation, cell
      migration, invasion and epithelial to mesenchymal transition, and is therefore
      essential to normal cell physiology. In addition, ILK is overexpressed or
      deregulated in a number of human cancers and when experimentally overexpressed
      leads to the acquisition of a number of oncogenic phenotypes, some of which, such
      as increased cell migration, are actin-dependent. Here we shall focus on the
      recent finding that ILK also regulates the microtubule cytoskeleton and is
      involved in mitotic spindle organization. Therefore its deregulation may also
      lead to errors in cell division causing genomic instability, potentially further
      contributing to cancer development. In light of these findings, the therapeutic
      potential of the anti-mitotic effects of genetic or pharmacological inhibition of
      ILK will also be discussed.

PMID- 19153671
TI  - Invadopodia: specialized tumor cell structures for the focal degradation of the
      extracellular matrix.
AB  - Invasive tumor-derived or transformed cells, cultured on a flat extracellular
      matrix substratum, extend specialized proteolytically active plasma membrane
      protrusions. These structures, termed invadopodia, are responsible for the focal
      degradation of the underlying substrate. Considerable progress has been made in
      recent years towards understanding the basic molecular components and regulatory
      circuits and the ultrastructural features of invadopodia. This has generated
      substantial interest in invadopodia as a paradigm to study the complex
      interactions between the intracellular trafficking, signal transduction and
      cytoskeleton regulation machineries; hopes are high that they may also represent
      valid biological targets to help advance the anti-cancer drug discovery process.
      Current knowledge will be reviewed here with an emphasis on the many open
      questions in invadopodia biology.

PMID- 19153672
TI  - Proteolytic interstitial cell migration: a five-step process.
AB  - Cell migration is a multi-step process that leads to the actin-driven
      translocation of cells on or through tissue substrate. Basic steps involved in
      cell migration have been defined for two-dimensional haptokinetic migration
      which, however, does not provide physical constraints imposed by three
      dimensional interstitial tissues. We here describe the process of pericellular
      proteolysis that leads to extracellular matrix (ECM) degradation and realignment
      during cell movement and integrate it into established steps of cell migration.
      After actin-driven leading edge protrusion (step I) and anterior formation of
      integrin-mediated focal interactions to the substrate (step II), ECM breakdown is
      focalized towards physical ECM barriers several micrometer rearward of the
      leading edge (step III). Actomyosin-mediated cell contraction (step IV) then
      leads to rear-end retraction and forward sliding of cell body and nucleus so that
      a small tube-like matrix defect bordered by realigned ECM fibers becomes apparent
      (step V). Pericellular proteolysis is thus integral to the migration cycle and
      serves to widen ECM gaps and thereby lowers physical stress upon the cell body,
      which ultimately leads to aligned higher-oder ECM patterns.

PMID- 19153674
TI  - The cytoskeleton and cancer.
AB  - Cancer is a disease in which many of the characteristics of normal cell behavior
      are lost or perturbed. Uncontrolled cell proliferation and inappropriate cell
      survival are common features of all cancers, but in addition defects in cellular
      morphogenesis that lead to tissue disruption, the acquisition of inappropriate
      migratory and invasive characteristics and the generation of genomic instability
      through defects in mitosis also accompany progression of the disease. This volume
      is focused on the actin and microtubule cytoskeletons, key players that underpin
      these cellular processes. Actin and tubulin form highly versatile, dynamic
      polymers that are capable of organizing cytoplasmic organelles and intracellular
      compartments, defining cell polarity and generating both pushing and contractile
      forces. In the cell cycle, these two cytoskeletal structures drive chromosomal
      separation and cell division. During morphogenesis, they determine cell shape and
      polarity, and promote stable cell-cell and cell-matrix adhesions through their
      interactions with cadherins and integrins, respectively. Finally, during cell
      migration they generate protrusive forces at the front and retraction forces at
      the rear. These are all aspects of cell behavior than often go awry in cancer.
      This volume brings together those interested in understanding the contribution of
      the actin and microtubule cytoskeletons to the cell biology of cancer.

PMID- 19153673
TI  - Mechanics, malignancy, and metastasis: the force journey of a tumor cell.
AB  - A cell undergoes many genetic and epigenetic changes as it transitions to
      malignancy. Malignant transformation is also accompanied by a progressive loss of
      tissue homeostasis and perturbations in tissue architecture that ultimately
      culminates in tumor cell invasion into the parenchyma and metastasis to distant
      organ sites. Increasingly, cancer biologists have begun to recognize that a
      critical component of this transformation journey involves marked alterations in
      the mechanical phenotype of the cell and its surrounding microenvironment. These
      mechanical differences include modifications in cell and tissue structure,
      adaptive force-induced changes in the environment, altered processing of
      micromechanical cues encoded in the extracellular matrix (ECM), and cell-directed
      remodeling of the extracellular stroma. Here, we review critical steps in this
      "force journey," including mechanical contributions to tissue dysplasia, invasion
      of the ECM, and metastasis. We discuss the biophysical basis of this force
      journey and present recent advances in the measurement of cellular mechanical
      properties in vitro and in vivo. We end by describing examples of molecular
      mechanisms through which tumor cells sense, process and respond to mechanical
      forces in their environment. While our understanding of the mechanical components
      of tumor growth, survival and motility remains in its infancy, considerable work
      has already yielded valuable insight into the molecular basis of force-dependent
      tumor pathophysiology, which offers new directions in cancer chemotherapeutics.

PMID- 19153675
TI  - Actin and microtubule cytoskeletons in the development and maintenance of cancer
      phenotypes. Preface.

PMID- 19153676
TI  - Surface ozone measurements in the southwest of the Iberian Peninsula (Huelva,
      Spain).
AB  - INTRODUCTION: Photochemical ozone pollution of the lower troposphere (LT) is a
      very complex process involving meteorological, topographic emissions and chemical
      parameters. Ozone is considered the most important air pollutant in rural,
      suburban and industrial areas of many sites in the world since it strongly
      affects human health, vegetation and forest ecosystems, and its increase during
      the last decades has been significant. In addition, ozone is a greenhouse gas
      that contributes to climate change. For these reasons, it is necessary to carry
      out investigations that determine the behaviour of ozone at different locations.
      The aim of this work is to understand the levels and temporal variations of
      surface ozone in an industrial-urban region of the Southwest Iberian Peninsula.
      MATERIALS AND METHODS: The study is based on ozone hourly data recorded during a
      6-year period, 2000 to 2005 at four stations and meteorological data from a
      coastal station. The stations used were El Arenosillo and Cartaya--both coastal
      stations, Huelva--an urban site and Valverde--an inland station 50 km away from
      the coastline. The general characteristics of the ozone series, seasonal and
      daily ozone cycles as well as number of exceedances of the threshold established
      in the European Ozone Directive have been calculated and analysed. RESULTS:
      Analysis of the meteorological data shows that winter-autumn seasons are governed
      by the movement of synoptic weather systems; however, in the spring-summer
      seasons, both synoptic and mesoescale conditions exist. Average hourly ozone
      concentrations range from 78.5 +/- 0.1 microg m(-3) at Valverde to 57.8 +/- 0.2
      microg m(-3) at Huelva. Ozone concentrations present a seasonal variability with
      higher values in summer months, while in wintertime, lower values are recorded. A
      seasonal daily evolution has also been found with minimum levels around 08:00
      UTC, which occurs approximately 1-1.5 h after sunrise, whereas the maximum is
      reached at about 16:00 UTC. Furthermore, during summer, the maximum value at El
      Arenosillo and Valverde stations remains very uniformed until 20:00 UTC. These
      levels could be due to the photochemical production in situ and also to the
      horizontal and vertical ozone transport at El Arenosillo from the reservoir
      layers in the sea and in the case of Valverde, the horizontal transport, thanks
      to the marine breeze. Finally, the data have been evaluated relative to the
      thresholds defined in the European Ozone Directive. The threshold to protect
      human health has been exceeded during the spring and summer months mainly at El
      Arenosillo and Valverde. The vegetation threshold has also been frequently
      exceeded, ranging from 131 days at Cartaya up to 266 days at Valverde.
      DISCUSSION: The results in the seasonal and daily variations demonstrate that El
      Arenosillo and Valverde stations show higher ozone concentrations than Cartaya
      and Huelva during the spring and summer months. Under meteorological conditions
      characterized by land-sea breeze circulation, the daytime sea breeze transports
      the emissions from urban and industrial sources in the SW further inland. Under
      this condition, the area located downwind to the NE is affected very easily by
      high ozone concentrations, which is the case for the Valverde station.
      Nevertheless, according to this circulation model, the El Arenosillo station
      located at the coast SE from these sources is not directly affected by their
      emissions. The ozone concentrations observed at El Arenosillo can be explained by
      the ozone residual layer over the sea, similar to other coastal sites in the
      Mediterranean basin. CONCLUSIONS: The temporal variations of the ozone
      concentrations have been studied at four measurement sites in the southwest of
      the Iberian Peninsula. The results obtained point out that industrial and urban
      emissions combined with specific meteorological conditions in spring and summer
      cause high ozone levels which exceed the recommended threshold limits and could
      affect the vegetation and human health in this area. RECOMMENDATIONS AND
      PERSPECTIVES: This work is the first investigation related to surface ozone in
      this region; therefore, the results obtained may be a useful tool to air quality
      managers and policy-makers to apply possible air control strategies towards a
      reduction of ozone exceedances and the impact on human health and vegetation. Due
      to the levels, variability and underlying boundary layer dynamics, it is
      necessary to extend this research in this geographical area with the purpose of
      improving the understanding of photochemical air pollution in the Western
      Mediterranean Basin and in the south of the Iberian Peninsula.

PMID- 19153677
TI  - Adherence to weekly oral bisphosphonate therapy: cost of wasted drugs and
      fractures.
AB  - In an observational cohort of patients treated with biphosphonates (BP), we
      observed that poor adherence to these drugs causes important expenditures in
      terms of avoidable fractures. Of particular interest are the amounts of money
      wasted by patients who did not take their BPs long enough to obtain a clinical
      benefit. INTRODUCTION: A large proportion of patients initiated with oral weekly
      BP therapy stop their treatment within the first year. The objective of this
      study was to estimate the impact of the poor adherence to BPs in terms of drug
      wasted and avoidable fractures. METHODS: The study was done on primary and
      secondary prevention cohorts from the Regie de l'assurance maladie du Quebec
      (Quebec). The concept of the "point of visual divergence" was used to determine
      the amount of wasted drug. The risk of fracture was estimated using Cox
      regression models. The hazard ratios of compliant patients (+80%) versus non
      compliant patients were used to estimate the number of fractures saved. RESULTS:
      The cost of wasted drugs was $25.87 per patient initiated in the primary
      prevention cohort and $30.52 in the secondary prevention cohort. If all patients
      had been compliant, 110 fractures would have been avoided in the primary
      prevention cohort and 19 fractures in the secondary prevention cohort. The cost
      of these avoidable fractures per patient initiated on BP therapy was $62.95 in
      primary prevention cohort and $330.84 in secondary prevention cohort.
      CONCLUSIONS: This study confirms that poor adherence to oral BPs leads to a
      significant waste of money and avoidable fractures.

PMID- 19153679
TI  - Future role for selective phospholipase A2 inhibitors in the prevention of
      atherosclerotic cardiovascular disease.

PMID- 19153678
TI  - Effects of long-term strontium ranelate treatment on vertebral fracture risk in
      postmenopausal women with osteoporosis.
AB  - SUMMARY: Vertebral fractures are a major adverse consequence of osteoporosis. In
      a large placebo-controlled trial in postmenopausal women with osteoporosis,
      strontium ranelate reduced vertebral fracture risk by 33% over 4 years,
      confirming the role of strontium ranelate as an effective long-term treatment in
      osteoporosis. INTRODUCTION: Osteoporotic vertebral fractures are associated with
      increased mortality, morbidity, and loss of quality-of-life (QoL). Strontium
      ranelate (2 g/day) was shown to prevent bone loss, increase bone strength, and
      reduce vertebral and peripheral fractures. The preplanned aim of this study was
      to evaluate long-term efficacy and safety of strontium ranelate. METHODS: A total
      of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate
      or placebo for 4 years, followed by a 1-year treatment-switch period for half of
      the patients. Primary efficacy criterion was incidence of patients with new
      vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were
      also evaluated. RESULTS: Over 4 years, risk of vertebral fracture was reduced by
      33% with strontium ranelate (risk reduction = 0.67, p < 0.001). Among patients
      with two or more prevalent vertebral fractures, risk reduction was 36% (p <
      0.001). QoL, assessed by the QUALIOST(R), was significantly better (p = 0.025),
      and patients without back pain were greater (p = 0.005) with strontium ranelate
      than placebo over 4 years. Lumbar BMD increased over 5 years in patients who
      continued with strontium ranelate, while it decreased in patients who switched to
      placebo. Emergent adverse events were similar between groups. CONCLUSION: In this
      4- and 5-year study, strontium ranelate is an effective and safe treatment for
      long-term treatment of osteoporosis in postmenopausal women.

PMID- 19153681
TI  - Online tools for predicting integral membrane proteins.
AB  - We identify and describe a set of tools readily available for integral membrane
      protein prediction. These tools address two problems: finding potential
      transmembrane proteins in a pool of new sequences, and identifying their
      transmembrane regions. All methods involve comparing the query protein against
      one or more target models. In the simplest of these, the target "model" is
      another protein sequence, while the more elaborate methods group together the
      entire set of t ansmembrane helical or transmembrane beta-barrel proteins. In
      general, prediction accuracy either in identifying new integral membrane proteins
      or transmembrane regions of known integral membrane proteins depends strongly on
      how closely the query fits the model. Because of this, the best approach is an
      opportunistic one: submit the protein of interest to all methods and choose the
      results with the highest confidence scores.

PMID- 19153680
TI  - Anti-factor VIII antibodies (Inhibitors) in hemophilia A: in dire need of basic
      and therapeutic research.

PMID- 19153682
TI  - In silico identification of novel G protein coupled receptors.
AB  - G-protein coupled receptors (GPCRs) are a superfamily of membrane integral
      proteins responsible for a large number of physiological functions. Approximately
      50% of marketed drugs are targeted toward a GPCR. Despite showing a high degree
      of structural homology, there is a large variance in sequence within the GPCR
      superfamily which has lead to difficulties in identifying and classifying
      potential new GPCR proteins. Here the various computational techniques that can
      be used to characterize a novel GPCR protein are discussed, including both
      alignment-based and alignment-free approaches. In addition, the application of
      homology modeling to building the three-dimensional structures of GPCRs is
      described.

PMID- 19153683
TI  - Transcriptome-based identification of candidate membrane proteins.
AB  - A full understanding of leukocyte responses to external stimuli requires
      knowledge of the full complement of proteins found on their surfaces. Systematic
      examination of the mammalian cell surfaces at the protein level is hampered by
      technical difficulties associated with proteomic analysis of so many membrane
      proteins and the large amounts of starting material required. The use of
      transcriptomic analyses avoids challenges associated with protein stability and
      separation and enables the inclusion of an amplification step; thus allowing the
      use of cell numbers applicable to the study of sub populations of, for example,
      primary lymphocytes. Here we present a transcriptomic methodology based on Serial
      Analysis of Gene Expression (SAGE) to recover an essentially complete and
      quantitative profile of mRNA species in a particular cell. We discuss how, using
      bioinformatic tools accessible to standard desktop computers, plasma membrane
      proteins can be identified in silico, from this list. While we describe the use
      of this approach to characterise the cell surface protein complement of a resting
      CD8(+) T-cell clone, it is theoretically applicable to any cell surface, where a
      suitable pure population of cells is available.

PMID- 19153684
TI  - Separation of thylakoid membrane proteins by sucrose gradient ultracentrifugation
      or blue native-SDS-PAGE two-dimensional electrophoresis.
AB  - Generally, a combination of two or more chromatographic and/or electrophoretic
      methods is conducted to separate membrane protein complexes. Here we describe how
      thylakoid membrane protein complexes from the photosynthetic apparatus can be
      successfully separated by two main steps: preparative methods that enable
      purification of membrane protein complexes in the native (intact) form, and
      analytical methods that allow resolution of each membrane protein. Thus,
      separation of intact supercomplexes was achieved by solubilisation of the sample
      using mild detergents followed either by sucrose gradient ultracentrifugation or
      by blue native gel (BNG) electrophoresis. Complexes, thus, recovered were then
      resolved further using either reversed phase liquid chromatography or SDS-PAGE
      respectively.

PMID- 19153685
TI  - Extraction of yeast mitochondrial membrane proteins by solubilization and
      detergent/polymer aqueous two-phase partitioning.
AB  - Identification and characterization of membrane proteins is of increasing
      importance in modern proteomic studies. It is of central interest to have access
      to methods that combine efficient solubilization with enrichment of proteins and
      intact protein complexes. Separation methods have been developed based on
      nondenaturing detergent extraction of yeast mitochondrial membrane proteins
      followed by enrichment of hydrophobic proteins in aqueous two-phase system.
      Combining the zwitterionic detergent Zwittergent 3-10 and the nonionic detergent
      Triton X-114 results in a complementary solubilization of proteins, which is
      similar to that of the anionic detergent sodium dodecyl sulfate (SDS) but with
      the important advantage of being nondenaturing. Detergent/polymer two-phase
      system partitioning offers removal of soluble proteins, which can be further
      improved by manipulation of the driving forces governing protein distribution
      between the phases. Integral and peripheral membrane protein subunits from intact
      membrane protein complexes partition to the detergent phase while soluble
      proteins are found in the polymer phase. A protocol is presented which combines
      nondenaturing solubilization of membrane proteins with extraction in
      detergent/polymer two-phase system for application in proteomic studies as a mild
      and efficient method for enrichment of membrane proteins and membrane protein
      complexes.

PMID- 19153686
TI  - 16-BAC/SDS-PAGE analysis of membrane proteins of yeast mitochondria purified by
      free flow electrophoresis.
AB  - Mitochondria are essential organelles in cellular metabolism. These organelles
      are bounded by two membranes, the outer and inner membrane. Especially the inner
      membrane comprises a high content of proteins, for example, the protein complexes
      of the respiratory chain. High-resolution separation and analysis of such
      membrane proteins, for example, by two-dimensional gel electrophoresis (2-DE), is
      hampered by their hydrophobicity and tendency for aggregation. Here, we describe
      the separation of mitochondrial membrane proteins of Saccharomyces cerevisiae by
      16-benzyldimethyl-n-hexadecylammonium chloride/sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (16-BAC/SDS-PAGE). This method enables the
      separation of membrane proteins owing to the solubilizing power of the ionic
      detergents 16-BAC and SDS, respectively. Mitochondria were isolated from yeast
      cultures by differential centrifugation and were further purified by free flow
      electrophoresis (FFE) in zone-electrophoretic mode (ZE). Subsequently, membrane
      proteins from ZE-FFE-purified mitochondria were enriched by carbonate extraction
      and subjected to 16-BAC/SDS-PAGE. The resulting protein spot patterns were
      visualized by a highly sensitive fluorescence stain with ruthenium-II
      bathophenantroline disulfonate chelate (RuBP), and by colloidal Coomassie
      staining. Proteins were identified by Maldi-Tof mass spectrometry and peptide
      mass fingerprinting.

PMID- 19153687
TI  - Sequential detergent extraction prior to mass spectrometry analysis.
AB  - Sequential detergent extraction of proteins from eukaryotic cells has been used
      to increase proteome coverage of 2D-PAGE. We have adapted sequential detergent
      extraction for use with the high-throughput non-electrophoretic proteomics method
      of liquid chromatography and electrospray ionisation tandem mass spectrometry.
      This method of extraction yields comprehensive proteomes that include up to twice
      as many membrane proteins as other published methods. Two thirds of these
      membrane proteins have more than one transmembrane domain and many of these have
      multiple transmembrane domains. Since sequential detergent extraction (SDE)
      separates proteins based upon their physicochemistry and sub-cellular
      localisation, this method also provides useful data about cellular localisation.

PMID- 19153688
TI  - Enrichment of brain plasma membranes by affinity two-phase partitioning.
AB  - Plasma membranes encompass a complex and varying set of proteins essential to
      life. In addition, plasma membrane proteins represent the majority of all known
      drug targets. The characterization of plasma membrane proteomes is, therefore, of
      eminent importance. A current bottleneck is the lack of efficient protocols to
      isolate plasma membranes from tissues or entire organs. To this end, we recently
      established a simple and effective isolation procedure which is based on aqueous
      polymer two-phase systems. In this chapter, we provide a detailed protocol for
      the isolation of plasma membranes from brain tissue, which could easily be
      adapted to other sources.

PMID- 19153689
TI  - Protocol to enrich and analyze plasma membrane proteins.
AB  - This chapter describes a procedure for isolation and analysis of fractions
      enriched in plasma membranes from minute amounts of tissue. It consists of a
      method for extraction and fractionation of membranes and a method for enzymatic
      digestion of membrane proteins without use of detergents. The method for
      isolation of membranes comprises of a stepwise depletion of nonintegral membrane
      molecules from entire tissue homogenate by high-salt, carbonate, and urea washes
      followed by a treatment of the membranes with sublytic concentrations of a
      detergent and enrichment of the plasma membranes by a density gradient
      fractionation. Fluorometric assays for protein content and plasma membrane marker
      activity allow calculation of the yield and extent of plasma membrane enrichment.
      Reduction, carboxymethylation, and digestion with endoproteinase Lys-C are
      carried out on nonsolubilized membranes. The entire procedure allows processing
      and preparation of samples from 10-20 mg tissue, and therefore, can be extremely
      helpful for proteomic profiling of biopsy-size clinical samples.

PMID- 19153690
TI  - Proteomic analysis of the lymphocyte plasma membrane using cell surface
      biotinylation and solution-phase isoelectric focusing.
AB  - Plasma membrane (PM) proteins are of particular interest to cell biologists
      because of their role in transducing information from the external environment to
      the cell interior, and because of their potential as therapeutic targets. The
      hydrophobicity and large size of these proteins renders their analysis by
      conventional proteomic approaches using 2D-electrophoresis problematic, limiting
      our ability to evaluate alterations of cell surface architecture as a function of
      varying physiological, pathological, or developmental state.In this chapter, we
      describe a simple method for enrichment and separation of plasma membrane
      proteins, prior to their identification by tandem mass spectrometry. Cell surface
      proteins are labeled with biotin using a reagent which does not enter the cell,
      purified by differential centrifugation and then affinity captured with
      streptavidin-agarose beads, before separation by a combination of solution-phase
      isoelectric focusing, and gradient gel electrophoresis, resulting in highly
      enriched membrane protein fractions suitable for characterization by mass
      spectrometry. We discuss the application of this protocol to the semiquantitative
      comparison of the plasma membrane proteins from resting and activated murine
      lymphocytes.

PMID- 19153691
TI  - Identification of target membrane proteins as detected by phage antibodies.
AB  - The discovery of novel target antigens for antibody-based immunotherapy is still
      a major challenge. Antibody phage display is one of the technologies that is
      widely applied for the identification of novel cell surface molecules on intact
      eukaryotic cells and many reports describe the isolation of phage-antibodies
      binding to restricted cell populations such as cells in a certain pathological
      condition. However, the transition from cell-specific phage antibodies to the
      identification of the target antigens is still a major hurdle. Herein a method is
      described for the identification of these cell surface molecules using two
      complementary technologies. A genomic approach based on expression cloning can be
      used when cDNA libraries and antigen-negative cells are available. Otherwise, a
      proteomic approach based on small scale immunoprecipitation followed by large
      scale purification and mass-spectrometry-based identification can be applied.
      Correct identification of the antigens is confirmed using technologies such as
      recombinant expression of the target antigen followed by immunoprecipitation or
      cDNA transfection and FACS analysis.

PMID- 19153692
TI  - Membrane protease degradomics: proteomic identification and quantification of
      cell surface protease substrates.
AB  - The modification of cell surface proteins by plasma membrane and soluble
      proteases is important for physiological and pathological processes. Methods to
      identify shed and soluble substrates are crucial to further define the substrate
      repertoire, termed the substrate degradome, of individual proteases. Identifying
      protease substrates is essential to elucidate protease function and involvement
      in different homeostatic and disease pathways. This characterisation is also
      crucial for drug target identification and validation, which would then allow the
      rational design of specific targeted inhibitors for therapeutic intervention. We
      describe two methods for identifying and quantifying shed cell surface protease
      targets in cultured cells utilising Isotope-Coded Affinity Tags (ICAT) and
      Isobaric Tags for Relative and Absolute Quantification (iTRAQ). As a model system
      to develop these techniques, we chose a cell-membrane expressed matrix
      metalloproteinase, MMP-14, but the concepts can be applied to proteases of other
      classes. By over-expression, or conversely inhibition, of a particular protease
      with careful selection of control conditions (e.g. vector or inactive protease)
      and differential labelling, shed proteins can be identified and quantified by
      mass spectrometry (MS), MS/MS fragmentation and database searching.

PMID- 19153693
TI  - Purification of basolateral integral membrane proteins by cationic colloidal
      silica-based apical membrane subtraction.
AB  - Epithelial cell polarity mediates many essential biological functions and
      perturbation of the apical/basolateral divide is a hallmark of epithelial to
      mesenchymal transition in carcinoma. Therefore, correct targeting of proteins to
      the apical and basolateral surfaces is essential to proper epithelial cell
      function. However, proteomic characterisation of apical/basolateral sorting has
      been largely ignored, due to ineffectual separation techniques and contamination
      of plasma-membrane preparations with housekeeping proteins. Here we describe a
      method that strips the apical membrane from the adherent cells and releases the
      intracellular contents, thereby leaving the basolateral membrane available for
      stringent washes and collection. Analysis of the basolateral membrane of an
      adherent colon adenocarcinoma cell line resulted in 66% of identified proteins
      being integral membrane proteins, which possessed either a transmembrane domain
      or lipid modification, including 35 CD antigens. Based on the abundance of
      peptides from basolateral marker proteins, this method efficiently captures
      basolateral integral membrane proteins, with minimal contamination from other
      membranes and basic proteins.

PMID- 19153694
TI  - Moving closer to the lipid raft proteome using quantitative proteomics.
AB  - Lipid rafts are small subdomains of the plasma membrane enriched in cholesterol,
      sphingolipids, saturated phospholipids and specific proteins. They are thought to
      act as coordination centres for signal transduction pathways so their protein
      composition is of particular biological interest. Rafts are refractory to
      solubilization in non-ionic detergents so they can be biochemically enriched by
      floatation on a sucrose density gradient but several other membranes co-migrate
      with rafts in such a procedure. Qualitative proteomic analysis of such detergent
      resistant membranes fails to distinguish true raft proteins from co-migrating
      contaminants. This chapter describes a quantitative proteomic application of
      Stable Isotope Labelling by Amino acids in Cell culture (SILAC) for
      distinguishing true raft proteins in detergent-resistant preparations.

PMID- 19153695
TI  - Use of sequential chemical extractions to purify nuclear membrane proteins for
      proteomics identification.
AB  - The nuclear envelope (NE) is a double membrane system that is both a part of the
      endoplasmic reticulum and part of the nucleus. As its constituent proteins tend
      to be highly complexed with nuclear and cytoplasmic components, it is notoriously
      difficult to purify. Two methods can reduce this difficulty for the
      identification of nuclear membrane proteins: comparison to contaminating
      membranes and chemical extractions to enrich for certain groups of proteins. The
      purification of nuclear envelopes and contaminating microsomal membranes is
      described here along with procedures for chemical extraction using salt and
      detergent, chaotropes, or alkaline solutions. Each extraction method enriches for
      different combinations of nuclear envelope proteins. Finally, we describe the
      analysis of these fractions with MudPIT, a proteomics methodology that avoids gel
      extraction of bands to facilitate identification of minor proteins and membrane
      proteins that do not resolve well on gels. Together these three approaches can
      significantly increase the output of proteomics studies aimed at identifying the
      protein complement of subcellular membrane systems.

PMID- 19153696
TI  - Isolation of extracellular membranous vesicles for proteomic analysis.
AB  - Membranous vesicles are constitutively released by a multitude of cell types.
      Following fusion of multivesicular bodies with the plasma membrane, endocytic
      vesicles, 30-90 nm in size termed exosomes are released extracellularly. Whilst
      several groups have reported the presence of exosomes in cell-culture conditioned
      medium, their biological and physiological functions still remain unclear. In
      addition, exosomes have been detected in body fluids associated with disease,
      further demonstrating their potential as diagnostic biomarkers. This protocol
      employs size filtration followed by ultracentrifugation to isolate and purify
      exosomes from the colon carcinoma cell line LIM 1215. Morphological visualisation
      and characterisation is based on electron microscopy and western blotting, whilst
      protein identification is achieved using a combination of 1D SDS-PAGE and LC
      MS/MS.

PMID- 19153697
TI  - Enrichment of human platelet membranes for proteomic analysis.
AB  - Platelets (thrombocytes) are the smallest human blood cells and are pivotal in
      processes of hemostasis and thrombosis. Central to their function, the activation
      of platelets includes a complex interplay of adhesion and signalling molecules
      mediated via the plasma and inner membrane. Because platelets are enucleated, the
      analysis of the proteome is the best way to approach their biology. Here, we
      employ mass spectrometry (MS)-based proteomics to characterise membrane proteins
      derived from non-stimulated human platelets. This protocol details the extraction
      and purification of platelet membrane proteins from whole blood using SDS-PAGE in
      conjunction with LC-MS/MS. This method allowed the identification, and
      characterization of 207 platelet membrane proteins (PMP) from approximately 9.95
      x 10(9) platelets (16).

PMID- 19153698
TI  - Detergents and chaotropes for protein solubilization before two-dimensional
      electrophoresis.
AB  - Because of the outstanding ability of two-dimensional electrophoresis to separate
      complex mixtures of intact proteins, it would be advantageous to apply it to all
      types of proteins, including hydrophobic and membrane proteins. Unfortunately,
      poor solubility hampers the analysis of these molecules. As these problems arise
      mainly in the extraction and isoelectric focusing steps, the solution is to
      improve protein solubility under the conditions prevailing during isoelectric
      focusing. This chapter describes the use of chaotropes and novel detergents to
      enhance protein solubility during sample extraction and isoelectric focussing,
      and discusses the contribution of these compounds to improving proteomic analysis
      of membrane proteins.

PMID- 19153699
TI  - Two-dimensional separation of membrane proteins by 16-BAC-SDS-PAGE.
AB  - Defining membrane proteomes is fundamental to our understanding of many
      physiological and pathophysiological processes. Their separation and
      identification is hence a key issue in basic and biomedical research. Due to
      their hydrophobic character, few high-resolution techniques for separation are
      available for qualitative and quantitative approaches. For gel-based methods, the
      two-dimensional 16-BAC/SDS-PAGE is the method of choice. This technique separates
      proteins in the first dimension using an acidic buffer system and the cationic
      detergent benzyldimethyl-n-hexadecylammonium chloride (16-BAC) and in the second
      dimension by SDS-PAGE. Here, we describe a detailed protocol for the separation
      of proteins by 16-BAC/SDS-PAGE.

PMID- 19153700
TI  - MudPIT analysis: application to human heart tissue.
AB  - Although two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) has been
      used as the standard proteomic approach for separating proteins in a complex
      mixture, this technique has many drawbacks. These include a limited molecular
      mass range, poor separation of highly acidic or basic proteins, and exclusion of
      the majority of membrane proteins from analysis. Considering the important
      functions of many membrane proteins, such as receptors, ion transporters, signal
      transducers, and cell adhesion proteins, it is increasingly important that these
      proteins are not excluded during the global proteomic analysis of cellular
      systems. Multidimensional Protein Identification Technology (MudPIT) offers a gel
      free alternative to 2D-PAGE for the analysis of both membrane and soluble
      proteins.The goal of this chapter is to provide detailed methods for using MudPIT
      to profile both membrane and soluble proteins in complex unfractionated samples.
      Methods discussed will include tissue homogenization, sample preparation, MudPIT,
      data analysis, and an application for the analysis of unfractionated total tissue
      homogenate from human heart.

PMID- 19153701
TI  - Liquid chromatography MALDI MS/MS for membrane proteome analysis.
AB  - Liquid chromatography (LC) can be combined with matrix-assisted laser-desorption
      ionization (MALDI) mass-spectrometry (MS) by using automated off-line fraction
      collection of eluates onto a MALDI plate. Commercial tandem MS systems are
      available for generating product ion spectra of MALDI-produced peptide ions. The
      MALDI MS/MS spectra can be searched against a proteome database for protein
      identification. In this chapter, a protocol of sequential solubilization and
      digestion of membrane proteins involving methanol- and SDS-assisted trypsin
      digestion and microwave-assisted acid hydrolysis is presented. The process of LC
      eluate deposition onto a MALDI plate along with practical considerations for
      achieving optimal performance of eluate deposition is described. Issues related
      to MALDI MS and MS/MS spectral acquisition are discussed. Database searching and
      manual inspection of MS/MS spectra of singly charged MALDI-produced peptide ions
      for positive protein identification are also addressed.

PMID- 19153702
TI  - Cysteinyl-tagging of integral membrane proteins for proteomic analysis using
      liquid chromatography-tandem mass spectrometry.
AB  - Membrane proteomic analysis is of considerable interest due to the role of
      receptors, ion channels, and membrane-associated proteins that are critical
      components in cellular control and differentiation. Consequently, proteomic
      investigations of membrane proteins under a variety of conditions and stimuli are
      being conducted. Although abundant and biologically significant, large-scale
      proteomic analysis of highly hydrophobic integral membrane proteins containing
      multiple transmembrane domains (TMDs) is more difficult and requires alternative
      methods than those routinely used for whole-cell proteomic studies. This chapter
      contains a method for extraction, solubilization, cysteinyl-labeling,
      proteolysis, and identification of hydrophobic integral membrane proteins for
      large-scale proteomic analysis using liquid chromatography-tandem mass
      spectrometry (LC/MS/MS). Application of this method enables proteome-wide
      identification of integral membrane proteins from both bacterial and plant
      tissues. The method is also amenable to quantifying integral membrane protein
      expression and posttranslational modifications using isotopically enriched media
      or various stable isotope-labeling and/or affinity isolation reagents such as
      iTRAQ and cICAT. Since the protocol can easily be extended to various cell and
      tissue types, we anticipate that the method will be of interest to those who are
      trying to characterize the membrane proteome and gain some insight regarding the
      role of receptors, ion channels, and other membrane proteins involved in signal
      transduction and cellular differentiation pathways.

PMID- 19153703
TI  - Quantitative proteomics analysis of pancreatic zymogen granule membrane proteins.
AB  - Pancreatic zymogen granules (ZG) are specialized for digestive enzyme storage and
      regulated secretion in the exocrine pancreas and are a classical model for
      studying secretory granule function. To understand the function of this
      organelle, we have conducted a proteomic study to identify the ZG membrane
      proteins from ZGs purified by Percoll gradient centrifugation. By combining
      multiple separation strategies including two-dimensional gel electrophoresis and
      two-dimensional liquid chromatography with tandem mass spectrometry (TMS), we
      identified 101 proteins from purified ZG membranes including a large number of
      proteins previously unknown on ZG membranes. To distinguish intrinsic membrane
      proteins from soluble and peripheral membrane proteins, a quantitative proteomics
      strategy was developed to measure the enrichment of intrinsic membrane proteins
      through the purification steps by labeling crude, KBr-, and Na(2)CO(3)-washed ZG
      membranes with multiplexed isobaric tags (iTRAQ), 114, 116 and 117, respectively.
      The proteins with 117:114 ratios greater than one correlated well with known or
      predicted intrinsic membrane proteins.

PMID- 19153704
TI  - [Is opioid-induced immunosuppression a clinically relevant problem? Innocent
      until proven guilty!].

PMID- 19153705
TI  - [Clinical evaluation of a pressure release valve for paediatric cuffed tracheal
      tubes].
AB  - OBJECTIVE: The safe use of cuffed tracheal tubes for children necessitates a cuff
      pressure limitation at 20-25 cmH2O. The aim of the study was to evaluate the
      reliability and benefit of a new cuff pressure release valve (opening pressure 20
      cmH2O) for children intubated with a cuffed tracheal tube. METHODS: In a
      prospective, observational trial cuff pressure was recorded in paediatric and
      adolescent patients intubated with a cuffed tracheal tube during
      sevoflurane/nitrous oxide anaesthesia. The cuff pressure release valve was
      interposed between the cuff manometer and the pilot balloon. In 25 patients
      measurements were started at the initial opening pressure (group A) and in a
      further 25 patients measurements were started at the minimal sealing cuff
      pressure (group B). RESULTS: A total of 50 patients, aged from 0.4 to 17.8 years
      (median 7.4 years) were enrolled in the study. The opening pressure measured
      (group A) was 19.7+/-0.8 cmH(2)O and the cuff sealing pressure (group B) was
      11.7+/-2.9 cmH2O (range 6-16 cmH2O). Mean cuff pressure values in group A were
      20.4+/-1.6 cmH2O and 16.5+/-3.3 cmH2O in group B. In one patient (group A) the
      cuff pressure exceeded 25 cmH2O and was manually decreased to 20 cmH2O. In total,
      24 filling procedures (group A 14; group B 10) were required during 103.1 h of
      investigation because of cuff pressure drop and audible air leakage, mainly
      caused by cuff pressure increases and consequent releases during patient
      positioning. CONCLUSION: Our data demonstrate that the tested cuff pressure
      release valve was useful and reliable to limit cuff pressure in tracheal
      intubated children and adolescents within an acceptable pressure range.

PMID- 19153706
TI  - [Surgery of malignant pancreatic tumors].
AB  - Ductal adenocarcinoma is the most common malignant tumor of the pancreas. Despite
      great efforts in basic and clinical pancreatic cancer research, the prognosis
      remains poor with an overall 5-year survival rate of less than 5%. Complete
      surgical resection represents the only curative treatment option and 5-year
      survival rates of 20-25% can be achieved following curative resection and
      adjuvant chemotherapy. Although pancreatic surgery is considered one of the most
      technically demanding and challenging procedures, there has been constant
      progress in surgical techniques and advances in perioperative care with a modern
      interdisciplinary approach including anesthesiology, oncology, radiology and
      nursing. This has reduced morbidity and especially mortality rates in high-volume
      centers. Among extended resection procedures multivisceral and venous resections
      are technically feasible and should be considered if a complete tumor resection
      can be achieved. Multimodal regimens have shown promising results, however, only
      adjuvant chemotherapy is supported by solid evidence from randomized controlled
      trials.

PMID- 19153708
TI  - Four rice QTL controlling number of spikelets per panicle expressed the
      characteristics of single Mendelian gene in near isogenic backgrounds.
AB  - Development of quantitative trait loci (QTL) near isogenic lines is a crucial
      step to QTL isolation using the strategy of map-based cloning. In this study, a
      recombinant inbred line (RIL) population derived from two indica rice varieties,
      Zhenshan 97 and HR5, was employed to map QTL for spikelets per panicle (SPP). One
      major QTL (qSPP7) and three minor QTL (qSPP1, qSPP2 and qSPP3) were identified on
      chromosomes 7, 1, 2 and 3, respectively. Four sets of near isogenic lines (NILs)
      BC(4)F(2) targeted for the four QTL were developed by following a standard
      procedure of consecutive backcross, respectively. These QTL were not only
      validated in corresponding NILs, but also explained amounts of phenotypic
      variation with much larger LOD scores compared with those identified in RILs. SPP
      in the four QTL-NILs expressed bimodal or discontinuous distributions and
      followed the expected segregation ratio of single Mendelian factor by progeny
      test. Finally, qSPP1, qSPP2, qSPP3 and qSPP7 were respectively mapped to a locus,
      0.5 cM from MRG2746, 0.6 cM from MRG2762, 0.8 cM from RM49 and 0.7 cM from
      MRG4436, as co-dominant markers on the basis of progeny tests. These results
      indicate no matter how small effect minor QTL is, QTL may still express the
      characteristics of single Mendelian factor in NILs and isolation of minor QTL
      will be possible using high quality NILs. Pyramiding these QTL into a variety
      will largely enhance rice grain yield.

PMID- 19153707
TI  - [A critical assessment of phytotherapy for prostate cancer].
AB  - Prostate cancer patients increasingly use complementary and alternative medicines
      to support the body's immune system in addition to conventional treatment to
      minimize morbidity associated with conventional treatment, to enhance the quality
      of life, and ultimately in the hope to cure cancer when conventional treatment
      fails. As there is a large variety of phytomedicines promoted as potential
      treatment for prostate cancer, the aim of this review was to differentiate
      between preventive and therapeutic approaches and evaluate which phytochemicals
      might be suited for therapy of prostate cancer. Therefore, preclinical in vitro
      and in vivo data as well as clinical trials with phytosubstances such as
      genistein, lycopene, epigallocatechin gallate, resveratrol, and mistletoe were
      assessed. The presented data show that at present there is no clinical evidence
      that phytochemicals might have a therapeutic use in prostate cancer in relation
      to reduction of tumor progression or improved survival. The question about an
      improved immune function or quality of life remains open. Potentially the use of
      phytochemicals could play a role in a preventive setting.

PMID- 19153709
TI  - Identification and mapping of Pi41, a major gene conferring resistance to rice
      blast in the Oryza sativa subsp. indica reference cultivar, 93-11.
AB  - The Oryza sativa subsp. indica reference cultivar (cv.), 93-11 is completely
      resistant to many Chinese isolates of the rice blast fungus. Resistance
      segregated in a 3:1 (resistance/susceptible) ratio in an F(2) population from the
      cross between 93-11 and the japonica reference cv. Nipponbare, when challenged
      with two independent blast isolates. The chromosomal location of this monogenic
      resistance was mapped to a region of the long arm of chromosome 12 by bulk
      segregant analysis, using 180 evenly distributed SSR markers. Five additional SSR
      loci and nine newly developed PCR-based markers allowed the target region to be
      reduced to ca. 1.8 cM, equivalent in Nipponbare to about 800 kb. In the reference
      sequence of Nipponbare, this region includes an NBS-LRR cluster of four genes.
      The known blast resistance gene Pi-GD-3 also maps in this region, but the 93-11
      resistance was distinguishable from Pi-GD-3 on the basis of race specificity. We
      have therefore named the 93-11 resistance Pi41. Seven markers completely linked
      to Pi41 will facilitate both marker-assisted breeding and gene isolation cloning.

PMID- 19153710
TI  - EST, COSII, and arbitrary gene markers give similar estimates of nucleotide
      diversity in cultivated tomato (Solanum lycopersicum L.).
AB  - Because cultivated tomato (Solanum lycopersicum L.) is low in genetic diversity,
      public, verified single nucleotide polymorphism (SNP) markers within the species
      are in demand. To promote marker development we resequenced approximately 23 kb
      in a diverse set of 31 tomato lines including TA496. Three classes of markers
      were sampled: (1) 26 expressed-sequence tag (EST), all of which were predicted to
      be polymorphic based on TA496, (2) 14 conserved ortholog set II (COSII) or
      unigene, and (3) ten published sequences, composed of nine fruit quality genes
      and one anonymous RFLP marker. The latter two types contained mostly noncoding
      DNA. In total, 154 SNPs and 34 indels were observed. The distributions of
      nucleotide diversity estimates among marker types were not significantly
      different from each other. Ascertainment bias of SNPs was evaluated for the EST
      markers. Despite the fact that the EST markers were developed using SNP
      prediction within a sample consisting of only one TA496 allele and one additional
      allele, the majority of polymorphisms in the 26 EST markers were represented
      among the other 30 tomato lines. Fifteen EST markers with published SNPs were
      more closely examined for bias. Mean SNP diversity observations were not
      significantly different between the original discovery sample of two lines (53
      SNPs) and the 31 line diversity panel (56 SNPs). Furthermore, TA496 shared its
      haplotype with at least one other line at 11 of the 15 markers. These data
      demonstrate that public EST databases and noncoding regions are a valuable source
      of unbiased SNP markers in tomato.

PMID- 19153712
TI  - Lectin extracted from Canavalia grandiflora seeds presents potential anti
      inflammatory and analgesic effects.
AB  - Neutrophil migration is responsible for tissue damage observed in inflammatory
      diseases and is also implicated in inflammatory nociception. The use of lectins
      has been demonstrated to be effective in different activities including anti
      inflammatory, antimicrobial, and in cancer therapy. In this study, we addressed
      the potential use of a lectin from Canavalia grandiflora seeds (ConGF) to control
      neutrophil migration and inflammatory hypernociception. Pretreatment of the
      animals intravenously (15 min before) with ConGF inhibited neutrophil migration
      to the peritoneal cavity in a dose-dependent fashion confirmed by an inhibition
      of rolling and adhesion of leukocytes by intravital microscopy. Another set of
      experiments showed that pretreatment of the animals with ConGF inhibited the
      mechanical hypernociception in mice induced by the i.pl. injection of carrageenan
      or formalin. This anti-nociceptive effect correlated with an effective blockade
      of neutrophil influx, as assessed by the hind paw tissue myeloperoxidase levels.
      Furthermore, ConGF had important inhibitory effects on the mouse carrageenan
      induced paw edema. In addition, animals treated with ConGF showed inhibition of
      cytokines release. In conclusion, we demonstrated that the lectin ConGF inhibits
      neutrophil migration and mechanical inflammatory hypernociception.

PMID- 19153713
TI  - Where is TRPV1 expressed in the bladder, do we see the real channel?
AB  - Transient receptor potential channel-vanilloid subfamily member 1 (TRPV1) is an
      important target in the treatment of bladder overactivity. This receptor is
      suggested to function as a mechanosensor in the normal bladder and to mediate the
      development of bladder overactivity during cystitis. Our aim was to determine the
      cellular distribution of TRPV1 in mouse and rat bladder tissue. We used three
      different commercial TRPV1 antibodies to perform immunohistochemistry on bladder
      tissue from rats and wild-type and TRPV1(-/-) mice, using trigeminal ganglia as a
      control tissue for TRPV1 expression. Although two of the antibodies seemed to
      react specifically in trigeminal ganglion tissue, all the antibodies produced a
      similar staining pattern in the urothelium of wild-type and TRPV1(-/-) mice.
      These data show that TRPV1 antibodies can cause an aspecific immunostaining in
      bladder tissue, urging for additional research to confirm the exact distribution
      of TRPV1 in bladder. In conclusion, we think that the use of negative controls on
      knockout mice, whenever available, is mandatory when conducting
      immunohistochemical localization studies.

PMID- 19153714
TI  - The transmembrane beta-subunits KCNE1, KCNE2, and DPP6 modify pharmacological
      effects of the antiarrhythmic agent tedisamil on the transient outward current
      Ito.
AB  - Accessory beta-subunits modulate the pharmacology of ion channel blockers. The
      aim was to investigate differences in effects of the antiarrhythmic agent and
      open-channel blocker tedisamil on transient outward current I(to) (Kv4.3) when
      coexpressed with beta-subunits potassium voltage-gated channel, Isk-related
      family, member 1 (KCNE1), potassium voltage-gated channel, Isk-related family,
      member 2 (KCNE2), or dipeptidyl-aminopeptidase-like protein 6 (DPP6) which
      modulate I(to) kinetics. Tedisamil inhibited I(to) with IC(50) values of 16
      microM for Kv4.3+KChIP2, 11 microM in the presence of KCNE1, and 14 microM for
      KCNE2. Values were higher in the presence of DPP6 or DPP6+KCNE2 (35 and 26
      microM). K(d) values of tedisamil binding and rate constants were not affected by
      KCNE or DPP6. I(to) kinetics were accelerated by KCNE and DPP6, inactivation to a
      larger extent with DPP6. Tedisamil did not affect activation time course but
      apparently accelerated inactivation in all channel subunit combinations tested.
      Deletion of the intracellular domain of KCNE2 or DPP6 resulted in slowing of
      kinetics and increased tedisamil sensitivity (IC(50) 4 and 7 microM). It is
      concluded that apparent effects of DPP6 and deletion mutants (KCNE2 and DPP6) are
      due to the acceleration or slowing effects of the beta-subunits on I(to)
      kinetics.

PMID- 19153716
TI  - Comparison of the discriminative stimulus effects of salvinorin A and its
      derivatives to U69,593 and U50,488 in rats.
AB  - BACKGROUND AND RATIONALE: Research interests regarding the psychopharmacology of
      salvinorin A have been motivated by the recreational use and widespread media
      focus on the hallucinogenic plant, Salvia divinorum. Additionally, kappa opioid
      (KOP) receptor ligands may have therapeutic potential in the treatment of some
      neuropsychiatric conditions, including drug dependence and mood disorders.
      Salvinorin A is a selective KOP agonist, but only a few studies have explored the
      discriminative stimulus effects of this compound. OBJECTIVE: This study compared
      the discriminative stimulus effects of salvinorin A and two synthetic derivatives
      of salvinorin B to the KOP agonists, U69,593 and U50,488. MATERIALS AND METHODS:
      Sixteen male Sprague-Dawley rats trained to discriminate U69,593 (0.13 mg/kg,
      s.c., N = 8) or U50,488 (3.0 mg/kg, i.p., N = 8) under a fixed-ratio 20 schedule
      of food reinforcement were administered substitution tests with salvinorin A
      (0.125-3.0 mg/kg, i.p.). The animals trained to discriminate U69,593 were also
      administered substitution tests with salvinorin B ethoxymethyl ether (0.005-0.10
      mg/kg, i.p.) and salvinorin B methoxymethyl ether (0.03-0.10 mg/kg, i.p.).
      Another eight rats were trained to discriminate 2.0 mg/kg salvinorin A and tested
      with U69,593 (0.04-0.32 mg/kg) and U50,488 (0.4-3.2 mg/kg). RESULTS: Salvinorin A
      and both synthetic derivatives of salvinorin B substituted completely for
      U69,593. Additionally, cross-generalization was observed between salvinorin A and
      both KOP agonists. CONCLUSION: These findings support previous reports indicating
      that the discriminative stimulus effects of salvinorin A are mediated by kappa
      receptors. Future studies may assist in the development and screening of
      salvinorin A analogs for potential pharmacotherapy.

PMID- 19153715
TI  - Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and
      intake in ethanol-dependent and nondependent rats.
AB  - RATIONALE: Two pharmacotherapies are approved for treating alcohol craving
      (acamprosate and naltrexone), but both have shown mixed findings in animals and
      humans. OBJECTIVES: The present experiments utilized a "reinforcer blocking"
      approach (i.e., rats were able to consume ethanol during treatment) to better
      understand the efficacy of these treatments for ethanol seeking and drinking
      using ethanol-dependent and nondependent rats. MATERIALS AND METHODS: In
      "nondependent" experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone
      0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant
      sessions with a low response requirement to gain access to reinforcers for 20
      min. For "dependent" experiments, rats were made dependent in vapor/inhalation
      chambers. RESULTS: Acamprosate and naltrexone had similar effects on intake in
      nondependent and dependent rats; neither drug was selective for ethanol over
      sucrose drinking. In nondependent animals, naltrexone was more efficacious at
      more doses than acamprosate, and acamprosate's effects were limited to a dose
      that also had adverse effects on body weight. Both pharmacotherapies showed more
      selectivity when examining reinforcer seeking. In nondependent rats, acamprosate
      and naltrexone had response-attenuating effects in ethanol, but not sucrose,
      groups. In dependent animals, acamprosate had selective effects limited to a
      decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol
      seeking in nondependent rats. CONCLUSIONS: The naltrexone-induced decreases in
      seeking suggested a change in incentive motivation which was selective for
      ethanol in nondependent rats. The "nondependent" paradigm may model early stages
      of "problem drinking" in humans, and the findings suggest that naltrexone could
      be a good intervention for this level of alcohol abuse and relapse prevention.

PMID- 19153717
TI  - Rapid determination of ascorbic acid, dehydroascorbic acid, and total vitamin C
      by electrochemiluminescence with a thin-layer electrochemical cell.
AB  - This paper reports on a rapid and sensitive method for the simultaneous
      determination of ascorbic acid (H(2)A), dehydroascorbic acid (DHA), and total
      vitamin C by electrochemiluminescence (ECL) using a thin-layer electrochemical
      cell. Significant ECL signals can be generated by the anodic oxidation of
      Ru(bpy)(3) (2+) in the presence of H(2)A or DHA in pH 8.8 phosphate buffer
      solution. Because of the extremely small dead volume of the thin-layer cell
      (approximately 1.5 microL), almost all amount of H(2)A is assumed to be
      completely oxidized to DHA with a short pre-electrolysis step. As a result, it is
      possible to determine the reductive vitamin C (H(2)A) by square wave voltammetry
      before the pre-electrolysis step, while total vitamin C (sum of H(2)A and DHA) is
      able to be determined at a subsequent ECL step. The method was employed for the
      determination of vitamin C in commercial beverages with the analytical results in
      good agreement with the certified values.

PMID- 19153718
TI  - Three-dimensional depth profiling of molecular structures.
AB  - Molecular time of flight secondary ion mass spectrometry (ToF-SIMS) imaging and
      cluster ion beam erosion are combined to perform a three-dimensional chemical
      analysis of molecular films. The resulting dataset allows a number of artifacts
      inherent in sputter depth profiling to be assessed. These artifacts arise from
      lateral inhomogeneities of either the erosion rate or the sample itself. Using a
      test structure based on a trehalose film deposited on Si, we demonstrate that the
      "local" depth resolution may approach values which are close to the physical
      limit introduced by the information depth of the (static) ToF-SIMS method itself.

PMID- 19153719
TI  - Affinity capturing for targeting proteins into micro and nanostructures.
AB  - Protein immobilization into micro and nanoscaled patterns opens exciting
      possibilities in fundamental and applied research. Developing efficient capturing
      techniques while preserving the structural and functional integrity of the
      proteins on surfaces is a key challenge for surface scientists. In this paper,
      current techniques for site-specific protein immobilization into engineered
      surface architectures are reviewed. Fundamental principles for functional protein
      immobilization on solid supports are discussed and popular affinity-based
      recognition pairs and their application for capturing proteins into nano and
      microstructures are presented.

PMID- 19153720
TI  - Fluorescence study of the dynamic interaction between E1(145-162) sequence of
      hepatitis GB virus C and liposomes.
AB  - The physicochemical characterization of the peptide sequence E1(145-162)
      corresponding to the structural protein E1 of the hepatitis G virus was done by
      studying its interaction with model membranes. Small unilamellar vesicles (SUVs)
      of dimyristoylphosphatidylglycerol or dimyristoylphosphatidylcholine were chosen
      as mimetic membranes. Peptide incorporation and location in the phospholipid
      bilayer was investigated by fluorescence anisotropy with SUVs labeled with
      diphenylhexatriene (DPH) or trimethylammonium-DPH. The addition of the peptide
      E1(145-162) showed significant changes in the anisotropy values of the probe
      located at the air/water interface. These results indicate that the peptide
      E1(145-162) preferably interacts with the lipid surface without penetrating
      inside the bilayer. A series of fluorescence experiments based on tryptophan
      peptide fluorescence were modeled by means of multivariate curve resolution
      alternating least squares (MCR-ALS) algorithm to further study the peptide
      interaction with bilayers at different temperatures. The preliminary results
      obtained with MCR-ALS showed how the peptide concentration decay is directly
      linked to the appearance of a new specie, which corresponds to the lipid-peptide
      binding. These results provide useful information for the design of synthetic
      immunopeptides that can be incorporated into a liposomal system with potential to
      promote a direct delivery of the membrane-incorporated immunogen to the
      immunocompetent cells, thus increasing the immuno response from the host.

PMID- 19153721
TI  - Characterization of lipid extracts from brain tissue and tumors using Raman
      spectroscopy and mass spectrometry.
AB  - Brain tissue is characterized by high lipid content. The amount of lipids
      decreases, and its composition changes in the most frequent primary brain tumor,
      the glioma. Scope of the current paper was to extract quantitatively lipids from
      porcine and human brain tissue as well as from five human gliomas using a
      modified protocol according to Folch. The lipid extracts were studied by Raman
      spectroscopy with 785 nm excitation and by mass spectrometry with electron impact
      ionization. Porcine and human brain tissues have similar water and lipid content
      and show similar Raman and mass spectra. In contrast, gliomas are characterized
      by increased water content and decreased lipid content. Elevated
      phosphatidylcholine to cholesterol ratios in lipid extracts of gliomas were
      indicated by Raman bands of the choline group and cholesterol. Due to its higher
      sensitivity, mass spectrometry detected increased levels of cholesterol ester
      relative to cholesterol in lipid extracts of gliomas. For comparison, thin tissue
      sections were prepared from the glioma specimens before lipid extraction;
      infrared spectroscopic images were recorded and analyzed by a supervised
      classification model. This study demonstrates how to improve the analysis of
      brain tumors and to complement the diagnosis of brain pathologies using a
      multimodal approach.

PMID- 19153722
TI  - X-ray diffraction and scanning electron microscopy of galvannealed coatings on
      steel.
AB  - The formation of Fe-Zn intermetallic compounds, as relevant in the commercial
      product galvannealed steel sheet, was investigated by scanning electron
      microscopy and different methods of X-ray diffraction. A scanning electron
      microscope with high resolution was applied to investigate the layers of the
      galvannealed coating and its topography. Grazing incidence X-ray diffraction
      (GID) was preferred over conventional Bragg-Brentano geometry for analysing thin
      crystalline layers because of its lower incidence angle alpha and its lower depth
      of information. Furthermore, in situ experiments at an environmental scanning
      electron microscope (ESEM) with an internal heating plate and at an X-ray
      diffractometer equipped with a high-temperature chamber were carried out. Thus,
      it was possible to investigate the phase evolution during heat treatment by X-ray
      diffraction and to display the growth of the zeta crystals in the ESEM.

PMID- 19153723
TI  - Dual coding of visual asymmetries in the pigeon brain: the interaction of bottom
      up and top-down systems.
AB  - The pigeon's visual system is an excellent model to investigate the ontogenetic
      and the neuronal foundations of cerebral asymmetries. Before hatching,
      lateralized visual stimulation induces structural asymmetries within the
      tectofugal pathway during a critical time window. Interhemispheric control
      mechanisms emerge presumably after hatching and stabilize these induced
      asymmetries. Once established, visual asymmetry in pigeons displays a left
      hemispheric dominance for complex learning and discrimination tasks and unravels
      how the interplay between bottom-up and top-down mechanisms generate a
      lateralized, hemispheric-specific visual analysis. The ascending visual
      (tectofugal) pathway displays cell size asymmetries and directs more bilateral
      visual information towards the left hemisphere. This bottom- up system is
      controlled by telencephalic top-down projections, which affect intra- and/or
      interhemispheric inhibitory systems in a presumably lateralized manner. Such a
      flexible organization allows the control of information transfer depending on the
      visual input and hence adapt the dominant processing mode to environmental
      requirements.

PMID- 19153724
TI  - Velocity control in Parkinson's disease: a quantitative analysis of isochrony in
      scribbling movements.
AB  - An experiment was conducted to contrast the motor performance of three groups (N
      = 20) of participants: (1) patients with confirmed Parkinson Disease (PD)
      diagnose; (2) age-matched controls; (3) young adults. The task consisted of
      scribbling freely for 10 s within circular frames of different sizes. Comparison
      among groups focused on the relation between the figural elements of the trace
      (overall size and trace length) and the velocity of the drawing movements.
      Results were analysed within the framework of previous work on normal individuals
      showing that instantaneous velocity of drawing movements depends jointly on trace
      curvature (Two-thirds Power Law) and trace extent (Isochrony principle). The
      motor behaviour of PD patients exhibited all classical symptoms of the disease
      (reduced average velocity, reduced fluency, micrographia). At a coarse level of
      analysis both isochrony and the dependence of velocity on curvature, which are
      supposed to reflect cortical mechanisms, were spared in PD patients. Instead,
      significant differences with respects to the control groups emerged from an in
      depth analysis of the velocity control suggesting that patients did not scale
      average velocity as effectively as controls. We factored out velocity control by
      distinguishing the influence of the broad context in which movement is planned-
      i.e. the size of the limiting frames--from the influence of the local context-
      i.e. the linear extent of the unit of motor action being executed. The balance
      between the two factors was found to be distinctively different in PD patients
      and controls. This difference is discussed in the light of current theorizing on
      the role of cortical and sub-cortical mechanisms in the aetiology of PD. We argue
      that the results are congruent with the notion that cortical mechanisms are
      responsible for generating a parametric template of the desired movement and the
      BG specify the actual spatio-temporal parameters through a multiplicative gain
      factor acting on both size and velocity.

PMID- 19153725
TI  - A longitudinal study of prospective control in catching by full-term and preterm
      infants.
AB  - Prospective control when catching moving toys was studied longitudinally in full
      term and preterm infants between the ages of 22 and 48 weeks. The toy's distance
      and time to the catching place and its velocity were explored as possible timing
      strategies used by infants to start their hand movement. The aim of the study was
      to find evidence for a shift in timing strategy and whether there were
      differences between full-term and preterm infants. In addition, it was
      investigated how infants continuously guided their hands to the toy and whether
      this guidance was influenced by their use of timing strategy. The toy approached
      the infants from the side with different constant velocities and constant
      accelerations. Results showed that there was little difference between full-term
      and preterm infants' use of timing strategies. Initially, infants used a distance
      or velocity-strategy, possibly causing them to have many unsuccessful catches.
      After a shift to a time-strategy, infants appeared to increase the number of
      successful catches and performed longer and more functional tau-couplings between
      the hand and the toy. One preterm infant did not switch to a time-strategy, and
      frequently missed the moving toy. The same infant also showed less functional tau
      coupling with non-controlled collisions between the hand and the toy. More follow
      up research is needed to investigate whether problems with extracting the
      relevant perceptual information for action could be an early indication of later
      perceptuo-motor difficulties.

PMID- 19153727
TI  - Identification and characterization of a novel nitrilase from Pseudomonas
      fluorescens Pf-5.
AB  - Nitrile groups are catabolized to the corresponding acid and ammonia through one
      step reaction involving a nitrilase. Here, we report the use of bioinformatic and
      biochemical tools to identify and characterize the nitrilase (NitPf5) from
      Pseudomonas fluorescens Pf-5. The nitPf5 gene was identified via sequence
      analysis of the whole genome of P. fluorescens Pf-5 and subsequently cloned and
      overexpressed in Escherichia coli. DNA sequence analysis revealed an open-reading
      frame of 921 bp, capable of encoding a polypeptide of 307 amino acids residues
      with a calculated isoelectric point of pH 5.4. The enzyme had an optimal pH and
      temperature of 7.0 degrees C and 45 degrees C, respectively, with a specific
      activity of 1.7 and 1.9 micromol min(-1) mg protein(-1) for succinonitrile and
      fumaronitrile, respectively. The molecular weight of the nitrilase as determined
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration
      chromatography was 33,000 and 138,000 Da, respectively, suggesting that the
      enzyme is homotetrameric. Among various nitriles, dinitriles were the preferred
      substrate of NitPf5 with a K (m) = 17.9 mM and k (cat)/K (m) = 0.5 mM(-1) s(-1)
      for succinonitrile. Homology modeling and docking studies of dinitrile and
      mononitrile substrate into the active site of NitPf5 shed light on the substrate
      specificity of NitPf5. Although nitrilases have been characterized from several
      other sources, P. fluorescens Pf-5 nitrilase NitPf5 is distinguished from other
      nitrilases by its high specific activity toward dinitriles, which make P.
      fluorescens NitPf5 useful for industrial applications, including enzymatic
      synthesis of various cyanocarboxylic acids.

PMID- 19153728
TI  - Construction of an Escherichia coli to Bacillus thuringiensis shuttle vector for
      large DNA fragments.
AB  - Shuttle vectors for Bacillus thuringiensis or Bacillus cereus usually cannot hold
      fragments larger than 20 kb. With the development of genome research, shuttle
      vectors with higher loading capacity are necessary. We constructed an Escherichia
      coli to B. thuringiensis shuttle vector, pEMB0557, with a large loading capacity.
      This vector incorporated the ori60 replicon from B. thuringiensis subsp. kurstaki
      YBT-1520, erythromycin resistance (B. thuringiensis), and chloromycetin
      resistance (E. coli) genes. A bacterial artificial chromosome library of B.
      thuringiensis strain CT-43 was constructed and pEMB0557 was able to accommodate
      at least a 70-kb DNA fragment. Simultaneously, the cry1B gene on a 40-kb fragment
      could express a 140-kDa protein in plasmid-cured B. thuringiensis BMB171. Due to
      its high capacity and utility in expressing exogenous genes, pEMB0557 will be
      useful in cloning (especially silencing genes) and expressing large DNA fragments
      (e.g., gene clusters) in B. thuringiensis. Plasmid pEMB0557 provides a new tool
      for B. thuringiensis genome or B. cereus group research.

PMID- 19153729
TI  - A flow injection analysis system with encapsulated high-density Saccharomyces
      cerevisiae cells for rapid determination of biochemical oxygen demand.
AB  - The biochemical oxygen demand (BOD) determination was studied using a novel flow
      injection analysis (FIA) system with encapsulated Saccharomyces cerevisiae cells
      and an oxygen electrode and was compared with conventional 5-day BOD tests. S.
      cerevisiae cells were packed in a calcium alginate capsule at a dry cell weight
      of 250 g/l of capsule core. The level of dissolved oxygen (DO) was reduced due to
      the enhanced respiratory activity of the microbial cells when the injected
      nutrient passed through the bioreactor. The decrease in DO (DeltaDO) was
      intensified with the amount of microbial cells packed in the bioreactor. However,
      the specific DeltaDO decreased as the amount of cells loaded in the bioreactor
      increased. The DeltaDO value was dependent on the pH and temperature of the
      mobile phase and reached its maximum value at 35 degrees C and pH 7-8. Also,
      DeltaDO became larger at longer response times as the flow rate of the mobile
      phase decreased. The measurement of DeltaDO was repeated more than six times
      consecutively using a 20-ppm standard glucose and glutamic acid solution, which
      confirmed the reproducibility with a standard deviation of 0.95%. A strong linear
      correlation between DeltaDO and BOD was also observed. The 5-day BOD values of
      actual water and wastewater samples were in accordance with the BOD values
      obtained by this FIA method using encapsulated S. cerevisiae cells. Unlike the
      cell-immobilized bead system, there was no contamination of the bioreactor
      resulting from any leak of yeast cells from the sensor capsules during BOD
      measurements.

PMID- 19153730
TI  - Development of a quantitative PCR method to differentiate between viable and
      nonviable bacteria in environmental water samples.
AB  - Ethidium monoazide bromide (EMA) treatment of pure culture and environmental
      waters at low concentrations (1.0-7.5 microg/ml) indicated effective enumeration
      of viable and viable but nonculturable Escherichia coli in pure cultures, creek
      waters, and secondary activated sludge effluent samples by quantitative
      polymerase chain reaction (qPCR) amplification of the uidA and fliC gene targets
      at turbidity values < 10 NTU. However, EMA treatment was not effective in primary
      clarifier and secondary trickling filter effluents where turbidities were > or =
      10 NTU. In viable pure cultures, rapidly dividing and senescent cells were most
      affected by increasing EMA concentrations. Amplification of heat-killed pure
      bacterial cultures decreased 4 to 6 logs depending on EMA concentration and
      culture age. The greatest difference was observed in 5-h cultures using 7.5
      microg/ml EMA. Turbidity (> or = 100 NTU) in environmental samples inhibited EMA
      effectiveness on viability discrimination. Enumeration of E. coli in certain
      wastewaters using EMA-qPCR was similar to culture suggesting that EMA treatment
      could be incorporated into qPCR assays for the quantification of viable bacteria
      increasing assay time no more than 30 min. Our results indicate that EMA can be
      used in routine qPCR assays, but optimum conditions for exposure must be
      identified for each sample type due to sample matrix effects such as turbidity.

PMID- 19153731
TI  - Hybrid PET-dynamic CECT in the management of breast cancer.

PMID- 19153732
TI  - What role for recombinant human TSH in the treatment of metastatic thyroid
      cancer?

PMID- 19153733
TI  - One-day or two-day procedure for sentinel node biopsy in melanoma?
AB  - PURPOSE: We compared the outcome of a 1-day and a 2-day sentinel node (SN) biopsy
      procedure, evaluated in terms of lymphoscintigraphic, surgical and pathological
      findings. METHODS: We studied 476 patients with melanoma from two melanoma
      centres using static scintigraphy and blue dye. A proportional odds model was
      used for statistical analysis. RESULTS: The number of SNs visualized at
      scintigraphy increased significantly with time from injection to scintigraphy and
      activity left in the patient at scintigraphy, and depended on the melanoma
      location. The number of SNs removed at surgery increased with the number of SNs
      visualized at scintigraphy and time from injection to surgery. The frequency of
      nodal metastasis increased with increasing thickness and Clark level of the
      melanoma, and was highest for two SNs visualized at scintigraphy. CONCLUSION:
      This study showed that early vs. late imaging and surgery do make a difference on
      the outcome of the SN procedure and confirmed the importance of the scintigraphic
      visualization of all true SNs.

PMID- 19153734
TI  - Cardiac and autonomic nerve function after reduced-intensity stem cell
      transplantation for hematologic malignancy in patients with pre-transplant
      cardiac dysfunction.
AB  - Recent reports have shown that cardiomyopathy caused by hemochromatosis in severe
      aplastic anemia is reversible after reduced-intensity allogeneic stem-cell
      transplantation (RIST). We comprehensively evaluated cardiac and autonomic nerve
      function to determine whether cardiac dysfunction due to causes other than
      hemochromatosis is attenuated after RIST. In five patients with cardiac
      dysfunction before transplant, we analyzed the changes in cardiac and autonomic
      nerve function after transplant, using electrocardiography (ECG),
      echocardiography, radionuclide angiography (RNA), serum markers, and heart rate
      variability (HRV), before and up to 100 days after transplant. There was no
      significant improvement in cardiac function in any patient and no significant
      alteration in ECG, echocardiogram, RNA, or serum markers. However, on time-domain
      analysis of HRV, the SD of normal-to-normal RR intervals (SDNN) and the
      coefficient of variation of the RR interval (CVRR) decreased significantly 30 and
      60 days after transplant (P = 0.04 and 0.01, respectively). Similarly, on
      frequency-domain analysis of HRV, low and high frequency power (LF and HF)
      significantly and temporarily decreased (P = 0.003 and 0.03, respectively).
      Notably, in one patient who had acute heart failure after transplantation, the
      values of SDNN, CVRR, r-MSSD, LF, and HF at 30 and 60 days after transplantation
      were the lowest of all the patients. In conclusion, this study suggests that (a)
      RIST is well-tolerated in patients with cardiac dysfunction, but we cannot expect
      improvement in cardiac dysfunction due to causes other than hemochromatosis; and
      (b) monitoring HRV may be useful in predicting cardiac events after RIST.

PMID- 19153735
TI  - Exposure of human leukemia NB4 cells to increasing concentrations of selenite
      switches the signaling from pro-survival to pro-apoptosis.
AB  - Selenium at low concentrations has a chemopreventive role against cancer, while
      at high concentrations, selenite exerts a direct antitumor effect. However, the
      mechanisms behind these effects remain elusive. In this study, we found that
      different concentrations of selenite triggered different signal pathways in human
      leukemia NB4 cells. Low concentrations of selenite elicited mild endoplasmic
      reticulum (ER) stress and mediated cell survival by activating unfolded protein
      response signaling, whereas high concentrations of selenite induced severe ER
      stress and caused cell death by activation of the pro-apoptotic transcription
      factors GADD153. In addition, selenite at low concentrations activated other anti
      apoptotic pathways, such as AKT and ERK, whereas high concentrations of selenite
      induced activation of p53 and oxidative stress, which mediated the antitumor
      activity of selenite by causing mitochondrial dysfunction and caspase activation.
      These findings uncover the molecular mechanisms of the chemopreventive and
      antitumor effects of different concentrations of selenite.

PMID- 19153736
TI  - Indomethacin overcomes doxorubicin resistance by decreasing intracellular content
      of glutathione and its conjugates with decreasing expression of gamma
      glutamylcysteine synthetase via promoter activity in doxorubicin-resistant
      leukemia cells.
AB  - Drug resistance continues to be a serious problem in cancer therapy. We
      investigated whether indomethacin, which inhibits cyclooxygenases, is able to
      overcome doxorubicin resistance in K562/ADR leukemia cells. Indomethacin at 10
      microM increased the cytotoxicity of doxorubicin and vincristine in K562/ADR
      cells. Intracellular glutathione content was elevated in K562/ADR cells.
      Indomethacin treatment decreased glutathione content and glutathione-conjugates
      in K562/ADR cells. Increased expression of gamma-glutamylcysteine synthetase
      (gamma-GCS) was observed in K562/ADR cells, but this expression was decreased by
      indomethacin treatment. The activity of the gamma-GCS promoter from K562/ADR
      cells decreased after indomethacin treatment in MDA231 cells. These data strongly
      suggest that the cyclooxygenase inhibitor indomethacin increases the cytotoxicity
      of doxorubicin by decreasing the intracellular contents of glutathione and its
      conjugates with decreasing expression of gamma-GCS by inhibiting gamma-GCS
      promoter activity.

PMID- 19153737
TI  - Adding low dose tacrolimus in rheumatoid arthritis patients with an inadequate
      response to tumor necrosis factor inhibitor therapies.
AB  - In the present study, we retrospectively evaluate the efficacy of low dose
      tacrolimus (TAC) as add-on therapy in refractory rheumatoid arthritis (RA)
      despite a combination of tumor necrosis factor (TNF) inhibitor and methotrexate
      (MTX) using consecutive case series of five patients with active RA (mean disease
      duration 2.3 years) despite MTX and TNF inhibitors for at least 3 months (mean
      9.5 months) treated with low dose TAC (1.5-2 mg/day) for at least 6 months (mean
      1.8 years). Clinical and radiographic efficacy was assessed according to the
      European league against rheumatism response criteria and the modified Sharp
      method, respectively. At 1 year, three patients reached to remission. The mean
      yearly progression of radiographic joint damage of all five patients after the
      onset of TAC was significantly decreased compared to that observed during anti
      TNF therapy without TAC (p = 0.04). One patient temporally discontinued the
      treatment because of herpes zoster. In RA patients with inadequate response to
      MTX and a TNF inhibitor, additions of low dose TAC markedly improved clinical
      variables including radiographic scores without remarkable detrimental effects.
      It seems that TAC in combination with MTX and TNF inhibitors may be a hopeful
      treatment option for RA patients with inadequate response to anti-TNF therapy.

PMID- 19153738
TI  - Neurological complications of ankylosing spondylitis: neurophysiological
      assessment.
AB  - Studies examined the neurological involvement of ankylosing spondylitis (AS) are
      limited. This study aimed to assess the frequency of myelopathy, radiculopathy
      and myopathy in AS correlating them to the clinical, radiological and laboratory
      parameters. Included were 24 patients with AS. Axial status was assessed using
      bath ankylosing spondylitis metrology index (BASMI). Patients underwent (a)
      standard cervical and lumbar spine and sacroiliac joint radiography, (b)
      somatosensory (SSEP) and magnetic motor (MEP) evoked potentials of upper and
      lower limbs, (c) electromyography (EMG) of trapezius and supraspinatus muscles.
      Patients' mean age and duration of illness were 36 and 5.99 years. Bath
      ankylosing spondylitis metrology index mean score was 4.6. Twenty-five percent (n
      = 6) of patients had neurological manifestations, 8.3% of them had myelopathy and
      16.7% had radiculopathy. Ossification of the posterior (OPLL) and anterior (OALL)
      longitudinal ligaments were found in 8.3% (n = 2) and 4.2% (n = 1). About 70.8%
      (n = 17) had >or=1 neurophysiological test abnormalities. Twelve patients (50%)
      had SSEP abnormalities, seven had prolonged central conduction time (CCT) of
      median and/or ulnar nerves suggesting cervical myelopathy. Six had delayed
      peripheral or root latencies at Erb's or interpeak latency (Erb's-C5) suggesting
      radiculopathy. Motor evoked potentials was abnormal in 54% (n = 13). Twelve (50%)
      and five (20.8%) patients had abnormal MEP of upper limbs and lower limbs,
      respectively. About 50% (n = 12) had myopathic features of trapezius and
      supraspinatus muscles. Only 8.3% (n = 2) had neuropathic features. We concluded
      that subclinical neurological complications are frequent in AS compared to
      clinically manifest complications. Somatosensory evoked potential and MEP are
      useful to identify AS patients prone to develop neurological complications.

PMID- 19153739
TI  - Analysis of genetic stability at SSR loci during somatic embryogenesis in
      maritime pine (Pinus pinaster).
AB  - Somatic embryogenesis (SE) is a propagation tool of particular interest for
      accelerating the deployment of new high-performance planting stock in
      multivarietal forestry. However, genetic conformity in in vitro propagated plants
      should be assessed as early as possible, especially in long-living trees such as
      conifers. The main objective of this work was to study such conformity based on
      genetic stability at simple sequence repeat (SSR) loci during somatic
      embryogenesis in maritime pine (Pinus pinaster Ait.). Embryogenic cell lines
      (ECLs) subjected to tissue proliferation during 6, 14 or 22 months, as well as
      emblings regenerated from several ECLs, were analyzed. Genetic variation at seven
      SSR loci was detected in ECLs under proliferation conditions for all time points,
      and in 5 out of 52 emblings recovered from somatic embryos. Three of these five
      emblings showed an abnormal phenotype consisting mainly of plagiotropism and loss
      of apical dominance. Despite the variation found in somatic embryogenesis-derived
      plant material, no correlation was established between genetic stability at the
      analyzed loci and abnormal embling phenotype, present in 64% of the emblings. The
      use of microsatellites in this work was efficient for monitoring mutation events
      during the somatic embryogenesis in P. pinaster. These molecular markers should
      be useful in the implementation of new breeding and deployment strategies for
      improved trees using SE.

PMID- 19153740
TI  - The promoter of the Arabidopsis thaliana BAN gene is active in proanthocyanidin
      accumulating cells of the Brassica napus seed coat.
AB  - As part of an ongoing research program dedicated to the understanding of
      proanthocyanidin (PA) accumulation in Brassica napus seed coat, transgenic
      rapeseed plants carrying a 2.3-kb fragment of the Arabidopsis thaliana BAN
      promoter (ProAtBAN) fused to the uidA reporter gene (GUS) were generated.
      Analysis of these plants revealed that ProAtBAN was activated in B. napus seed
      coat, following a spatio-temporal pattern that was very similar to the PA
      deposition profile in rapeseed and also to the one previously described in
      Arabidopsis. ProAtBAN activity occurred as soon as the early stages of
      embryogenesis and was restricted to the cells where PAs were shown to accumulate.
      Therefore, the Arabidopsis BAN promoter can be used to trigger gene expression in
      B. napus seed coat for both genetic engineering and functional validation of
      candidate genes. In addition, these data strongly suggest that the
      transcriptional regulatory network of the BAN gene is conserved between
      Arabidopsis and rapeseed. This is consistent with the fact that similarity
      searches of the public rapeseed sequence databases allowed recovering the
      rapeseed homologs for several BAN regulators, namely TT1, TT2, TT8, TT16 and
      TTG1, which have been previously described in Arabidopsis.

PMID- 19153741
TI  - Is there a role for virtual otoscopy in the preoperative assessment of the
      ossicular chain in chronic suppurative otitis media? Comparison of HRCT and
      virtual otoscopy with surgical findings.
AB  - The aim of this study was to assess the role of virtual otoscopy and 3D ossicular
      reconstruction in the preoperative assessment of the ossicles in chronic
      suppurative otitis media. Thirty three patients of chronic suppurative otitis
      media with conductive deafness (air-bone gap > 35 dB) were included in this
      prospective study. All patients underwent axial multidetector CT. The axial CT
      data set was utilized for multiplanar 2D reformations as well as virtual otoscopy
      (VO) and 3D reconstructions. The imaging findings on these two techniques were
      read independently by two radiologists with respect to different parts of the
      ossicular chain by using a three-point scoring system and were compared with
      surgical findings. Both imaging techniques had comparable accuracy for evaluation
      of larger ossicular parts. However, for evaluation of stapes superstructure,
      VO/3D images were more accurate (85.29%) than 2D images (76.97%). Assessment of
      the lenticular process and incudostapedial joint by HRCT and 2D reformatted
      images was not reliable (P > 0.1); however, significant correlation (P < 0.001)
      was present between VO/3D and the operative findings. Virtual otoscopy improves
      evaluation of the ossicular chain particularly that of smaller structures such as
      the lenticular process, incudostapedial joint and stapes superstructure which may
      influence decisions regarding planning of ossiculoplasty.

PMID- 19153742
TI  - Development of molecular imaging in the European radiological community.
AB  - The recent and concomitant advances in molecular biology and imaging for
      diagnosis and therapy will place in vivo imaging techniques at the centre of
      their clinical transfer. Before that, a wide range of multidisciplinary
      preclinical research is already taking place. The involvement of radiologists in
      this new field of imaging sciences is therefore absolutely mandatory during these
      two phases of development. Achievement of such objectives requires the refinement
      of strategy within the European radiological community and the European Society
      of Radiology (ESR) will have to drive a number of actions to stimulate the
      younger generation of radiologists and to facilitate their access to knowledge.
      For that purpose, a molecular imaging (MI) subcommittee of the ESR Research
      Committee based on a group of involved radiologists will be constituted to
      develop contacts with other constitutive committees and associated societies to
      provide proposals to our community.

PMID- 19153743
TI  - Comparison of four embolic materials for portal vein embolization: experimental
      study in pigs.
AB  - Different embolic materials for portal vein embolization (PVE) were evaluated.
      Twenty pigs received left and median PVE. Hydrophilic phosphorylcholine, N-butyl
      cyanoacrylate, hydrophilic gel, and polyvinyl alcohol (PVA) particles measuring
      either 50-150 microm or 700-900 microm were used in five pigs each. Portography
      and portal vein pressure measurement were performed before, immediately after
      PVE, and before being euthanized at day 7. Tissue wedges from embolized, and non
      embolized liver were obtained for pathology. After complete embolization,
      recanalization occurred at 7 days in one gel and one 700-900 PVA embolization.
      Post-PVE increase in portal pressure was found in all groups (p = 0.01). The area
      of the hepatic lobules in non-embolized liver was larger than in the embolized
      liver in all groups (p = 0.001). The ratios of the areas between non
      embolized/embolized livers were 1.65, 2.19, 1.57, and 1.32 for gel, NBCA, 50-150
      PVA and 700-900 PVA, respectively; the ratios of fibrosis between the embolized
      and non-embolized livers were 1.37, 3.01, 3.49, and 2.11 for gel, NBCA, 50-150
      PVA and 700-900 PVA, respectively. Hepatic lobules in non-embolized liver were
      significantly larger with NBCA than in other groups (p = 0.01). Fibrosis in
      embolized liver was significantly higher for NBCA and 50-150 PVA (p = 0.002). The
      most severe changes in embolized and non-embolized liver were induced by 50-150
      PVA and NCBA PVE.

PMID- 19153744
TI  - Dual-energy CT iodine overlay technique for characterization of renal masses as
      cyst or solid: a phantom feasibility study.
AB  - The aim of this study was to assess the ability of dual-energy computed
      tomography (DECT) to classify phantom renal lesions as cysts or enhancing masses.
      Six cylinders ranging in diameter from 0.5 to 3.0 cm were filled with distilled
      water or titrated iodinated contrast solutions with CT attenuation values at 120
      kVp of 0 Hounsfield units (HU) for a cyst proxy or 10, 20, or 40 HU to represent
      enhancing masses. These were placed in a 12-cm-diameter renal phantom containing
      pureed beef mixed with iodinated contrast medium to simulate enhancing renal
      parenchyma of 100 and 250 HU and submerged within a 28-cm water bath. These
      combinations produced 48 individual phantom renal lesions of differing sizes,
      internal and parenchymal enhancement (12 cysts and 36 enhancing masses). DECT
      using 80 and 140 kVp was performed on a dual-source CT scanner. Commercial
      software created a color-encoded overlay indicating the location of iodine within
      the phantom. The lesions were individually graded as a cyst or enhancing mass by
      blinded, consensus interpretation of two genitourinary radiologists. Thirty-five
      of 36 enhancing masses and 10/12 cysts were correctly identified, equating to a
      sensitivity and specificity of 97% (95% CI 84-100%) and 83% (95% CI 51-97%),
      respectively. All lesions of 20- and 40-HU enhancement and 92% of 10-HU lesions
      were identified correctly. In a phantom model, the DECT iodine overlay technique
      is highly sensitive in detecting enhancing renal masses. Refinement of the
      technique remains necessary to improve specificity. If validated in patients,
      this may obviate the need for unenhanced acquisitions for renal mass
      characterization.

PMID- 19153745
TI  - Ultrasound-guided removal of foreign bodies: personal experience.
AB  - Foreign bodies (FBs) retained in the soft tissues are a common reason for medical
      consultation, and usually consist of wooden or metal splinters or glass shards.
      Failure to remove foreign bodies is likely to give rise to acute or late
      complications, such as allergies, inflammation or infection, that may be severe.
      The surgical removal of an FB is invasive, costly and technically challenging.
      The procedure may fail in some cases and carries the risk of complications. Our
      study describes a technique for the ultrasound-guided removal of an FB, devised
      from our experience, and demonstrates its advantages over the standard surgical
      procedure. Sixty-two patients (43 males and 19 females aged from 9 to 65 years,
      median age 31 years) presented at our institution between October 2005 and June
      2008 with suspected foreign bodies retained in the soft tissues of various body
      districts. Radiographic and/or ultrasound diagnosis was established by a
      radiologist expert in musculoskeletal sonography. The same radiologist helped by
      a nurse subsequently undertook the ultrasound-guided removal in the outpatient's
      clinic according to the technique described in the paper. ATL 5000 and PHILIPS
      iu22 ultrasound systems were used with high-frequency linear-array probes,
      sterile material, local anaesthetic (lidocaine 2%), scapels and surgical forceps.
      Antibiotic prophylaxis with amoxicillin and clavulanic acid were prescribed to
      all patients for 7 days after the procedure. Ninety-five FBs (39 glass, 35 metal,
      17 vegetable, 2 plastic, 2 stone) were successfully removed under ultrasound
      guidance in all patients and the procedure took between 15 and 30 min. No
      complications arose either during or after the procedure. Seventy-five skin
      incisions were made and the wounds closed with Steri-Strips in 73/75 cases,
      whereas skin sutures were used in 2/75 cases. No complications arose either
      during or after the procedure. Ultrasound-guided removal of an FB retained in the
      soft tissues is a good alternative to surgery as is its relatively
      straightforward, inexpensive, repeatable and carries a low risk of complications.
      In addition, failure to remove an FB does not preclude traditional surgical
      removal. The advantages of this real-time procedure and the use of small
      instruments minimize bleeding time and avoid injury to surrounding structures.
      Patient compliance is enhanced by the fact that the procedure has little or no
      aesthetic impact. These encouraging results suggest ultrasound-guided removal as
      a first-choice procedure for the extraction of foreign bodies.

PMID- 19153746
TI  - Epithelioid hemangioendothelioma of thoracic vertebra: a case report (2008: 11b).
AB  - Epithelioid hemangioendothelioma is a rare, low-grade malignant
      hemangioendothelioma first reported in 1982. The disease is more likely to occur
      between 20 and 30 years with a 2:1 male-to-female ratio. Epithelioid
      hemangioendothelioma may occur in multiple organs and tissues, but it rarely
      involves the skeleton. We present a case in a thoracic vertebra.

PMID- 19153748
TI  - [Visual ergonomy and flying safety. The importance of recognizing the
      instruments].
AB  - While flying, more than 90% of all relevant information reaches the pilots
      visually, the so-called primary flight display providing the most important
      information. The size, brightness, contrast, and color perception of these
      instruments are important for precise recognition. We discuss the results from a
      study of new flying instruments.

PMID- 19153749
TI  - The Siberian timberman Acanthocinus aedilis: a freeze-tolerant beetle with low
      supercooling points.
AB  - Larvae of the Siberian timberman beetle Acanthocinus aedilis display a number of
      unique features, which may have important implications for the field of cold
      hardiness in general. Their supercooling points are scattered over a wide
      temperature range, and some individuals have supercooling points in the low range
      of other longhorn beetles. However, they differ from other longhorn beetles in
      being tolerant to freezing, and in the frozen state they tolerate cooling to
      below -37 degrees C. In this respect they also differ from the European timberman
      beetles, which have moderate supercooling capacity and die if they freeze. The
      combination of freezing tolerance and low supercooling points is unusual and
      shows that freezing at a high subzero temperature is not an absolute requirement
      for freezing tolerance. Like other longhorn beetles, but in contrast to other
      freeze-tolerant insects, the larvae of the Siberian timberman have a low
      cuticular water permeability and can thus stay supercooled for long periods
      without a great water loss. This suggests that a major function of the
      extracellular ice nucleators of some freeze-tolerant insects may be to prevent
      intolerable water loss in insects with high cuticular water permeability, rather
      than to create a protective extracellular freezing as has generally been assumed.
      The freezing tolerance of the Siberian timberman larvae is likely to be an
      adaptation to the extreme winter cold of Siberia.

PMID- 19153750
TI  - The management of completely resected childhood intracranial ependymoma: the
      argument for observation only.
AB  - INTRODUCTION: The management of children with completely resected intracranial
      ependymomas is controversial. We favor deferring adjuvant radiotherapy in low
      risk patients, whereas others recommend radiotherapy. REVIEW: This article
      reviews the available evidence for and against deferring radiotherapy in children
      with low-risk completely resected childhood ependymomas.

PMID- 19153751
TI  - A review on the management of epilepsy associated with hypothalamic hamartomas.
AB  - INTRODUCTION: Hypothalamic hamartomas are rare congenital malformations located
      in the region of the tuber cinereum and third ventricle. Patients may be
      asymptomatic, but the usual presentation is gelastic seizures, precocious
      puberty, and/or developmental delay. CLINICAL PRESENTATION: Without surgical
      intervention, the gelastic seizures, which are typically present in childhood,
      may progress to other seizure types, including generalized epilepsy, and are
      generally refractory to antiepileptic drugs. SUMMARY: This review will discuss
      the clinical and electrophysiologic aspects of these lesions, as well as
      treatment options, including surgery, endoscopy, and radiosurgery.

PMID- 19153752
TI  - Rasmussen encephalitis: long-term outcome after surgery.
AB  - BACKGROUND AND PURPOSE: Rasmussen encephalitis (RE) is characterized by
      intractable epilepsy, progressive hemiparesis, and unilateral hemispheric
      atrophy. The progression of the symptoms to significant neurological impairment
      usually occurs within months to a few years. RE causes are unknown, although
      evidence of an autoimmune process has been extensively described in the
      literature. Antiepileptic drugs are usually not effective to control seizures or
      cerebral atrophy; despite data supporting a beneficial effect of early
      immunosuppressive and immunomodulatory interventions, for intractable seizures in
      RE patients with advanced disease, epilepsy surgery in the form of hemispheric
      disconnection has been considered the treatment of choice. This work describes
      the clinical and electrographic analyses, as well as the post-operative evolution
      of patients with RE. MATERIALS AND METHODS: This work includes all the patients
      with RE evaluated from January 1995 to January 2008 by the Ribeirao Preto
      Epilepsy Surgery Program (CIREP), taking variables such as gender; age at
      epilepsy onset; seizure semiology; seizure frequency; interictal and ictal
      electroencephalographic (EEG) findings; age at surgery, when done; duration of
      epilepsy; surgery complications; follow-up duration; anatomo-pathological
      findings; post-surgery seizure; language and cognitive outcome; and anti
      epileptic drug treatment after surgery into account. RESULTS: Twenty-five
      patients were evaluated; thirteen were female. Mean age of epilepsy onset was
      4.4+/-2.0 years. There were no differences between patients with slow and fast
      evolution with respect to age of epilepsy onset (p=0.79), age at surgery
      (p=0.24), duration of epilepsy (0.06), and follow-up (p=0.40). There were no
      correlations between the presence of bilateral EEG abnormalities or the absence
      of spikes and post-operative seizure outcome (p=0.06). Immunomodulatory therapy
      was tried in 12 patients (48%). Twenty-three patients underwent surgery. The mean
      follow-up was 63.3 months. Eleven patients had total seizure control. Twelve
      individuals persisted with seizures consisting of mild facial jerks (six
      patients), occasional hemigeneralized tonic-clonic seizures (three patients), and
      frequent tonic-clonic seizures (three patients). Mental and language impairment
      was observed in 15 and 12 patients, after surgery, respectively. Eight patients
      presented post-operative cognitive decline, while only two patients had cognitive
      improvement. Comparing pre- and post-operative language deficits, 66.7% of the 12
      patients with language disturbance did not improve after surgery. CONCLUSIONS:
      This retrospective study reported the clinical and electrographic analysis, as
      well as the evolution of 23 patients with RE. Patients were divided into two
      groups: fast evolution and slow evolution to hemiparesis and epilepsia partialis
      continua. These groups may represent different RE substrates. Fourteen patients
      achieved satisfactory seizure control, three patients had partial response to
      surgery, and five patients had maintenance of the pre-operative condition. All
      patients with left-side involvement presented with some language disturbance,
      which did not improve after surgery in 66.6% of patients. Cognitive evaluation
      showed that the majority of the patients did not have any significant
      improvement, and 38.1% had cognitive deterioration after surgery.

PMID- 19153753
TI  - [Imaging techniques for giant cell arteritis. Ultrasound and MRI].
AB  - This article summarizes the examination technique, typical findings,
      interpretation and limitations of ultrasound diagnosis in patients with giant
      cell arteritis. Colour-coded sonography of the temporal artery has gained
      increasing attention. If experienced ultrasound examiners are available,
      diagnosis of giant cell arteritis in patients with a typical clinical
      constellation can be made based solely on sonographic findings, in particular by
      a hypoechogenic halo. The hitherto probably under-diagnosed large vessel variant
      of giant cell arteritis shows characteristic findings with a simple and quick
      ultrasound examination of the proximal arm arteries. High resolution MRI has been
      shown to be a promising technique for non-invasive imaging of giant cell
      arteritis. Mural inflammatory changes of the superficial temporal arteries can be
      depicted and the cranial involvement pattern can be readily assessed and in
      combination with MR angiography extracranial involvement can be determined within
      the same investigation. Aortitis is a feared complication of giant cell arteritis
      but can be detected and inflammatory stenoses of the aortic branch vessels can
      also be revealed. In the hands of an experienced operator ultrasonography can be
      regarded as the non-invasive imaging modality of first choice whereas MRI is more
      expensive and may not be as widely available. However, its imaging acquisition is
      standardized and is more observer-independent. Reading of the images is a routine
      task for a vascular radiologist and larger areas of the vasculature can be
      simultaneously assessed.

PMID- 19153754
TI  - Aggressive angiomyxoma of vulva recurring 8 years after initial diagnosis.
AB  - BACKGROUND: Aggressive angiomyxoma is an uncommon soft tissue tumor which
      preferentially involves pelvic and vulvoperineal regions of young adult females.
      The typical characteristics include gelatinous appearance and locally
      infiltrative nature without evidence of nuclear atypia or mitosis. Treatment
      involves surgery, but local recurrence is high in spite of apparently complete
      surgical resection. CASE: A 28-year-old woman who had had a history of surgically
      excised aggressive angiomyxoma of vulva presented with a complaint of vulvar
      mass. The mass was removed and histopathologic examination revealed an aggressive
      angiomyxoma without necrosis, atypia, and mitosis. CONCLUSION: Aggressive
      angiomyxoma should be kept in mind when an asymptomatic and slow-growing vulvar
      mass is detected in young females. The surgery should aim wide local excision and
      long-term follow-up is necessary due to high rate of local recurrence.

PMID- 19153755
TI  - Ancillary p16(INK4a) adds no meaningful value to the performance of ER/PR/Vim/CEA
      panel in distinguishing between primary endocervical and endometrial
      adenocarcinomas in a tissue microarray study.
AB  - PURPOSE: Endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA)
      are uterine malignancies that have differing biological behavior. The choice of
      appropriate therapeutic plan depends indeed on the tumor's site of origin. In
      this study, we not only compare the individual expression status of five
      immunomarkers (ER, PR, Vim, CEA, and p16(INK4a)), but also evaluate whether
      p16(INK4a) adds value to the ER/PR/Vim/CEA panel characteristics in
      distinguishing between primary ECA and EMA. METHODS: A tissue microarray (TMA)
      was constructed using paraffin-embedded, formalin-fixed tissues from 35
      hysterectomy specimens, including 14 ECA and 21 EMA. TMA sections were
      immunostained with five anti-bodies, by avidin-biotin complex (ABC) method for
      antigen visualization. The staining intensity and area extent of the
      immunohistochemical (IHC) reactions were appraised by using the semi-quantitative
      scoring system. RESULTS: The four respective markers (ER, PR, Vim, CEA) and their
      combined panel expressions showed significant (p < 0.05) frequency differences
      between ECA and EMA tumors. The p16(INK4a) marker also revealed a significant
      frequency difference (p < 0.05) between the two sites of origin, but did not
      demonstrate to have any supplementary value to the 4-marker panel. CONCLUSION:
      According to our data, when there is histomorphological and clinical doubt as to
      the primary site of origin, we recommend that the conventional 4-marker
      (ER/PR/Vim/CEA) panel is appropriate. Ancillary p16(INK4a)-marker testing does
      not add value to the 4-marker panel in distinguishing between primary ECA and
      EMA.

PMID- 19153756
TI  - How reliable are the risk estimates for X-ray examinations in forensic age
      estimations? A safety update.
AB  - Possible biological side effects of exposure to X-rays are stochastic effects
      such as carcinogenesis and genetic alterations. In recent years, a number of new
      studies have been published about the special cancer risk that children may
      suffer from diagnostic X-rays. Children and adolescents who constitute many of
      the probands in forensic age-estimation proceedings are considerably more
      sensitive to the carcinogenic risks of ionizing radiation than adults.
      Established doses for X-ray examinations in forensic age estimations vary from
      less than 0.1 microSv (left hand X-ray) up to more than 800 microSv (computed
      tomography). Computed tomography in children, as a relatively high-dose
      procedure, is of particular interest because the doses involved are near to the
      lower limit of the doses observed and analyzed in A-bombing survivor studies.
      From these studies, direct epidemiological data exist concerning the lifetime
      cancer risk. Since there is no medical indication for forensic age examinations,
      it should be stressed that only safe methods are generally acceptable. This paper
      reviews current knowledge on cancer risks associated with diagnostic radiation
      and aims to help forensic experts, dentists, and pediatricians evaluate the risk
      from radiation when using X-rays in age-estimation procedures.

PMID- 19153757
TI  - Frequent spontaneous eyeblink activity associated with reduced conjunctival
      surface (trigeminal nerve) tactile sensitivity.
AB  - BACKGROUND: A number of recent studies have reported high spontaneous eyeblink
      rate (SEBR) values in apparently normal subjects, but the reasons for this are
      unclear. METHODS: An assessment was made of SEBR, in 60 educated adult male
      subjects aged between 22 and 40 years, over a period of 5 min in silence. Half of
      the subjects were classified as having frequent eyeblink activity. All subjects
      also had their corneal and conjunctival touch (tactile) sensitivity assessed with
      a Cochet-Bonnet aesthesiometer immediately after the video recording of SEBR.
      RESULTS: SEBR ranged from 4.6 to 43.5 (mean 18.6) eyeblinks/min. The SEBR was
      26.8 +/- 6.0 eyeblinks/min for those with frequent eyeblink activity as compared
      to just 10.3 +/- 3.5 eyeblinks/min for those with normal eyeblink activity (p <
      0.001). There was no difference in palpebral aperture or exposed ocular surface
      area between the two groups. The average central corneal sensitivity was only
      marginally different between the two groups (56.8 +/- 2.8 mm vs 58.5 +/- 2.3 mm)
      but the conjunctival threshold sensitivity was substantially different (at 23.8
      +/- 4.3 mm vs 28.5 +/- 3.5 mm; p < 0.001). SEBR was inversely correlated with the
      conjunctival sensitivity in those with frequent eyeblink activity (p < 0.001).
      CONCLUSIONS: Our study provides a clue as to the mechanism of inhibition of
      spontaneous eyeblink activity, namely that a certain level of ocular surface
      (conjunctival) sensitivity is required to keep SEBR low.

PMID- 19153758
TI  - Systemic hypoxia affects cardiac autonomic activity and vascular hemodynamic
      control modulated by physical stimulation.
AB  - This study investigates how various hypoxic interventions affect cardiac
      autonomic activity and hemodynamic control during posture change and the Valsalva
      maneuver. Ten healthy sedentary men exposed to 12, 15 and 21% O(2) for 1 h in a
      normobaric hypoxia chamber in a random order. Before and after various O(2)
      concentrations were administered, subjects performed the sit-up test and Valsalva
      maneuver, respectively. An impedance plethysmography was utilized to measure
      blood pressure (BP) and vascular hemodynamics, whereas spectral analysis of heart
      rate variability (HRV) was performed to determine cardiac autonomic activity.
      Analytical results can be summarized as follows: while the patient rests in a
      supine position, exposure to 12% O(2) reduces the ratio of lower to upper
      extremity systolic BP, which is accompanied by (1) suppressed arterial reactive
      hyperemia and increased venous flow resistance, as well as (2) decreased total
      power and high frequency (HF) and increased low frequency (LF) and the ratio of
      LF to HF. Moreover, the hypoxia-induced changes of time and frequency domains in
      HRV at resting supine disappear following the sit-up test, whereas this hypoxic
      exposure attenuates the BP and heart rate responses to the Valsalva maneuver.
      Conversely, resting and physical stimuli-mediated HRV and vascular hemodynamic
      values are unaltered by both 15 and 21% O(2) exposures. We conclude that acute
      hypoxic exposure affects cardiovascular autonomic functions, with reactions
      determined by the intervening O(2) concentrations. Moreover, the BP and cardiac
      autonomic responses to 12% O(2), but not 15% O(2), exposure are depressed while
      performing posture change and the Valsalva maneuver.

PMID- 19153759
TI  - Effects of strength training and detraining on regional muscle in young and older
      men and women.
AB  - To examine the effects of 9 weeks of strength training (ST) and 31 weeks of
      detraining on regional muscle area in young and older men and women, three
      regions of the quadriceps muscle area (proximal, middle, and distal) were
      measured via MRI in 11 men ages 20-30, 11 men ages 65-75, 10 women ages 20-30,
      and 11 women ages 65-75. These effects were assessed by determining the
      difference between the control limb and the trained limb (T-UT) at all three time
      points. This design provided control for possible influences of biological,
      methodological, seasonal variations, as well as influences due to attention or
      genetic differences that commonly occur between experimental and control groups.
      There were no significant differences in any of the three regions at any of the
      three time points, when comparing subjects by age. However, men had significantly
      greater T-UT CSA at the after ST time point [6.9 (3.7) cm(2)] when compared with
      women [2.8 (3.7) cm(2), P < 0.05]. Baseline T-UT CSA was higher than after
      detraining T-UT CSA for young men in the proximal and middle regions [0.1 (3.6),
      0.4 (3.6) cm(2) vs. 2.8 (4.0), 2.4 (3.6) cm(2), P < 0.05], but there were no
      significant differences within the other three groups. These data indicate that
      sex may influence changes in regional CSA after ST, whereas age does not
      influence regional muscle gain or loss due to ST or detraining.

PMID- 19153760
TI  - Anatomical predictors of maximum isometric and concentric knee extensor moment.
AB  - The most important anatomical determinants of in vivo joint moment magnitude have
      yet to be defined. Relationships between maximal knee extensor moment and
      quadriceps muscle volume, anatomical (ACSA) and physiological (PCSA) cross
      sectional area, muscle architecture and moment arm (MA) were compared. Nineteen
      untrained men and women performed maximal isokinetic knee extensions under
      isometric conditions (90 degrees joint angle) and at 30 degrees and 300 degrees
      s(-1). Magnetic resonance and ultrasound imaging techniques were used to measure
      vastus lateralis PCSA and fascicle length (FL), quadriceps ACSA, volume and
      patellar tendon MA. Muscle volume was the best predictor of extensor moment
      measured isometrically (R(2) = 0.60) and at 30 degrees s(-1)(R (2) = 0.74). PCSA
      x FL was the best predictor of moment at 300 degrees s(-1) (R(2) = 0.59). MA was
      not an important predictor. ACSA was the second best predictor at all three
      speeds and could be recommended as an ideal measure given its relative ease of
      measurement.

PMID- 19153761
TI  - Physical exercise increases mitochondrial function and reduces oxidative damage
      in skeletal muscle.
AB  - The present study investigated mitochondrial adaptations and oxidative damage
      after 4 and 8 weeks of running training in skeletal muscle of mice. Twenty-one
      male mice (CF1, 30-35 g) were distributed into the following groups (n = 7):
      untrained (UT); trained-4 weeks (T4); trained-8 weeks (T8). Forty-eight hours
      after the last training session the animals were killed by decapitation and
      quadriceps (red portion) were removed and stored at -70 degrees C. Succinate
      dehydrogenase (SDH), complexes I, II, II-III and IV, lipoperoxidation (TBARS),
      protein carbonyls (PC) and total thiol content were measured. Results show that
      endurance training (8-wk) increases the SDH activity and complexes (I, II, III,
      IV), decreases oxidative damage (TBARS, CP) and increases total thiol content in
      skeletal muscle when compared to untrained animals. In conclusion, eight weeks of
      running training are necessary for increases in mitochondrial respiratory chain
      enzyme activities to occur, in association with decreased oxidative damage.

PMID- 19153762
TI  - Learning flexible sensori-motor mappings in a complex network.
AB  - Given the complex structure of the brain, how can synaptic plasticity explain the
      learning and forgetting of associations when these are continuously changing? We
      address this question by studying different reinforcement learning rules in a
      multilayer network in order to reproduce monkey behavior in a visuomotor
      association task. Our model can only reproduce the learning performance of the
      monkey if the synaptic modifications depend on the pre- and postsynaptic
      activity, and if the intrinsic level of stochasticity is low. This favored
      learning rule is based on reward modulated Hebbian synaptic plasticity and shows
      the interesting feature that the learning performance does not substantially
      degrade when adding layers to the network, even for a complex problem.

PMID- 19153763
TI  - The systems analysis approach to mechanosensory coding.
AB  - An important problem in neuroscience is to obtain quantitative knowledge of how
      information is represented, or encoded, in the signals that nerve cells process
      and transmit. Sensory receptors have provided important models for the study of
      neural coding because their inputs can often be relatively easily controlled and
      measured, while the resultant activity is recorded. A variety of engineering
      concepts have been successfully applied to physiological sciences, particularly
      those related to control of dynamic systems. Linear systems analysis was one of
      the earliest methods used to probe sensory coding, and measurements such as step
      responses and frequency responses have become standard tools for describing
      sensory functions. Modern systems analysis has evolved to provide accurate and
      efficient linear identification of encoding in sensory receptors that use either
      graded potentials or action potentials. It has also led to nonlinear systems
      analysis, the creation of parametric nonlinear models, and measures of
      information coding by sensory neurons. These methods promise to provide important
      new knowledge about sensory systems in the future, especially when complemented
      with parallel biophysical and molecular studies of sensory neurons.
      Mechanoreceptors provided some of the earliest preparations for the investigation
      of neural coding, and both the linear and nonlinear properties of wide variety of
      vertebrate and invertebrate mechanoreceptors continue to be explored.

PMID- 19153764
TI  - Ciliar functions in the nephron.
AB  - The primary cilium is a microtubule-based nonmotile organelle that is found on
      most cells in the mammalian body. Once regarded as a vestigial organelle, it has
      been recently shown to play unforeseen roles in mammalian physiology and tissue
      homeostasis. In kidney epithelial cells, the primary cilium plays a fundamental
      role in tubule organization and function and it is now considered to serve as a
      versatile mechanosensor and chemosensor. Diseases related to kidney primary cilia
      include autosomal polycystic kidney disease, recessive polycystic kidney disease,
      Bardet-Biedl syndrome, and nephronophthisis. Multiple proteins whose functions
      are disrupted in cystic kidney diseases have been localized in the primary
      cilium. This review provides a general introduction to the cell biology and
      function of renal primary cilia and an overview of cilia-related kidney diseases.

PMID- 19153765
TI  - Indigenous traditional medicine: in vitro anti-giardial activity of plants used
      in the treatment of diarrhea.
AB  - The ethnopharmacology for treatment of parasitic infections facilitates and
      directs the search for new chemical entities. In this direction, this study
      evaluated the cytotoxicity in vitro, against trophozoites of Giardia lamblia, of
      aqueous extracts of leaves Achyrocline satureioides (Lam.) DC., barks of Eugenia
      uniflora L., aerial parts of Foeniculum vulgare Miller, and barks of Psidium
      guajava L. These plants are traditionally used for the treatment of diarrhea by
      the indigenous population Mbya-Guarani, located at the Lomba do Pinheiro, Porto
      Alegre, Rio Grande do Sul, Brazil. The in vitro susceptibility qualitative
      analysis of G. lamblia to aqueous extracts was performed in serial dilutions from
      2.5 to 0.02 mg/mL. Results revealed the minimal inhibitory concentrations: 0.313
      mg/mL for A. satureioides and E. uniflora, 0.02 mg/mL for P. guajava, and F.
      vulgare did not present any cytotoxic effect. Quantitative assays of viable
      trophozoites, showed that A. satureioides presented the highest cytotoxic effect
      (93.5%), followed by P. guajava (82.2%), and E. uniflora (67.3%). Indigenous
      Guarani use mainly A. satureioides for the treatment of diarrhea, revealing the
      conformity with results obtained in vitro. Bioguided assays are necessary to
      identify the compounds responsible for the activity of the aqueous extract of A.
      satureioides.

PMID- 19153766
TI  - The CCTTT pentanucleotide microsatellite in iNOS promoter influences the clinical
      outcome in P. falciparum infection.
AB  - To assess the hypothesis that nitric oxide (NO) is critical in the pathogenesis
      of cerebral malaria, we analyzed those single nucleotide polymorphisms (SNPs) and
      microsatellite (MS) of the promoter region of inducible nitric oxide synthase
      (iNOS) gene which are known to enhance the NO production in vivo. A total of 428
      (204 severe, 224 mild) adult patients living in the eastern part of India were
      analyzed. The single nucleotide substitutions -954G-->C was found to be very
      rare, and -1173C-->T was absent in this population. But interestingly, longer
      forms of MS were found to be significantly associated with severe malaria (OR =
      2.89, 95% CI = 1.955-4.295, P < 0.0001), and the linear regression analysis
      revealed that the risk of severe malaria significantly increases as the summed
      repeat number in an individual increase (OR = 1.16, P = 0.0013). Further, the
      median plasma level of nitrate/nitrite (NOx) was observed to be high in mild
      patients compared to severe patients, and the level of parasitemia was
      significantly low among mild patients than severe ones. These findings suggest
      that the CCTTT repeats in iNOS may play a key role in the pathogenesis of severe
      malaria.

PMID- 19153768
TI  - An invasive dandelion unilaterally reduces the reproduction of a native congener
      through competition for pollination.
AB  - The impact of invasive alien species on native species is of increasing global
      concern. Invasive plants have various negative effects on natives through
      competition; however, relatively little is known about competition for
      pollination. The relationship between Japanese native dandelions (Taraxacum spp.)
      and invasive congeners may be a typical case of such an interaction. For example,
      native dandelions are being replaced by invasive congeners, especially in urban
      and suburban areas of Japan. To explain this phenomenon, we hypothesized that
      when natives are mixed with attractive invasives, natives may suffer from reduced
      seed set because invasives deprive natives of pollinators or because pollinators
      frequently move between species, resulting in interspecific pollen transfer. To
      test this hypothesis, we studied the effect of the invasive dandelion T.
      officinale on the pollination and seed set of the native T. japonicum using
      artificial arrays of monospecific and mixed-species plots as well as natural
      populations. Taraxacum officinale attracted more pollinator visits, perhaps
      because it produced more nectar than T. japonicum. The number of pollinator
      visits to T. japonicum was reduced when the congeners were grown together, and
      pollinators moved frequently between the two species. The proportion of seed set
      for T. japonicum was reduced in the presence of T. officinale in both artificial
      arrays and natural populations. These results support our hypothesis that
      interspecific competition for pollination plays an important role in the recent
      replacement of native dandelions by invasive congeners in Japan. Because invasive
      dandelions are apomicts, negative effects are incurred only by sexual natives.
      Thus, this system can be recognized as a rare case of interspecific interaction
      through pollination.

PMID- 19153767
TI  - Dissection of the Candida albicans class I chitin synthase promoters.
AB  - Maintenance of the integrity of the cell wall in fungi is essential. One
      mechanism that cells use to maintain cell wall integrity in response to cell wall
      damage is to up-regulate chitin synthesis. In Candida albicans, the PKC cell wall
      integrity, Ca(2+)/calcineurin and high osmolarity glycerol (HOG) signalling
      pathways co-ordinately regulate chitin synthesis in response to cell wall stress.
      The transcription factors downstream of these pathways and their DNA binding
      sites within the promoters of target genes are well characterised in
      Saccharomyces cerevisiae, but not in C. albicans. The promoters of the C.
      albicans class I CHS genes (CaCHS2 and CaCHS8) were functionally dissected with
      the aim of identifying and characterising the transcription factors and promoter
      elements that mediate the transcriptional up-regulation of CaCHS2 and CaCHS8 in
      response to cell wall stress. This analysis provided evidence that the PKC cell
      wall integrity pathway may operate through RLM1-elements in the CaCHS2 and CaCHS8
      promoters, but that promoter sequences that respond to the Ca(2+)/calcineurin and
      HOG signalling pathways in S. cerevisiae did not directly regulate chitin
      synthase 2 and 8 gene transcription in C. albicans.

PMID- 19153769
TI  - Improved glutathione production by gene expression in Pichia pastoris.
AB  - To utilize Pichia pastoris to produce glutathione, an intracellular expression
      vector harboring two genes (gsh1 and gsh2) from Saccharomyces cerevisiae encoding
      enzymes involved in glutathione synthesis and regulated by the glyceraldehyde-3
      phosphate dehydrogenase (GAP) promoter was transformed into P. pastoris GS115.
      Through Zeocin resistance and expression screening, a transformant that had
      higher glutathione yield (217 mg/L) in flask culture than the host strain was
      obtained. In fed-batch culture process, this recombinant strain displayed high
      activity for converting precursor amino acids into glutathione. The glutathione
      yield and biomass achieved 4.15 g/L and 98.15 g (dry cell weight, DCW)/L,
      respectively, after 50 h fermentation combined with addition of three amino acids
      (15 mmol/L glutamic acid, 15 mmol/L cysteine, and 15 mmol/L glycine).

PMID- 19153770
TI  - Kinetic analysis of hybridoma cells viability under mechanical shear stress with
      and without serum protection.
AB  - The effect of a well-defined mild shear stress on hybridoma cell viability (HB
      8852) in a serum-free culture medium has been analysed, and the role as shear
      protector of different concentrations of fetal bovine serum have been studied.
      Samples harvested from cultures in their late exponential growth phase, were
      subjected in a rheometer to a constant shear stress of 0.41 +/- 0.02 Pa, and the
      evolution of viable and total cell concentrations was determined and compared
      with static controls. A simple segregated kinetic model for the viable and dead
      cells was used to know the effect of serum concentration on the specific cell
      growth and death rate of the cells.

PMID- 19153771
TI  - Coenzyme Q10 production by Rhodobacter sphaeroides in stirred tank and in airlift
      bioreactor.
AB  - A higher Coenzyme Q(10) (CoQ(10)) concentration of 25.04 mg/l was found in
      airlift bioreactor than the value of 18.11 mg/l obtained in stirred tank under
      the aerobic-dark cultivation of Rhodobacter sphaeroides. Aeration rate didn't
      show obvious impact to CoQ(10) production in airlift bioreactor. The fed-batch
      operation in airlift bioreactor could increase the biomass concentration and led
      to the maximum CoQ(10) concentration of 33.91 mg/l measured, but a lower CoQ(10)
      cell content (3.5 mg CoQ(10)/DCW) was observed in the fed-batch operation as
      compared to the batch operation. To enhance the CoQ(10) content, an aeration
      change strategy was proposed in the fed-batch operation of airlift bioreactor.
      This strategy led to the maximum CoQ(10) concentration of 45.65 mg/l, a 35%
      increase as compared to the simple fed-batch operation. The results of this study
      suggested that a fed-batch operation in airlift bioreactor accompanying aeration
      change could be suitable for CoQ(10) production.

PMID- 19153772
TI  - Recent advances in chronic dialysis and renal transplantation in children.

PMID- 19153773
TI  - A fatal case of cerebral oedema with hyponatraemia and massive polyuria after
      renal transplantation.
AB  - We report the case of a child who died from severe cerebral oedema in the context
      of hyponatraemia and extreme polyuria immediately after renal transplantation.
      The patient was treated according to a standard post-transplantation protocol,
      receiving 0.45% saline solution for urine output replacement. The case highlights
      the dangers of massive fluid therapy in the context of polyuria and, therefore,
      the need for intensive monitoring.

PMID- 19153774
TI  - Transient parenchymal defects may occur in kidney transplants during urine
      infections.

PMID- 19153775
TI  - Increased nitric oxide production by T- and B-cells in idiopathic nephrotic
      syndrome.
AB  - The pathogenesis of idiopathic nephrotic syndrome (INS) remains unclear. To study
      the role of nitric oxide (NO) in INS, we measured intracellular NO produced by T-
      and B-cells using a novel fluorescent indicator. Twelve children with INS (mean
      age 7.3 years; group A-1: in relapse, group A-2: in remission) were enrolled in
      the study together with 16 children with other renal diseases (9.5 years; group
      B) and 42 healthy control children (7.7 years; group C). The amount of NO
      produced by CD3+ cells (T-cells) and CD19+ cells (B-cells) and of plasma NO(x)
      was measured by flow cytometry and colorimetry, respectively. The average amount
      of NO produced by CD3+ and CD19+ cells in group A-1 subjects was significantly
      higher than that produced by these cells in group A-2 and B patients and the
      healthy controls (group C), respectively (P < 0.01), and it decreased after the
      patients achieved remission (P < 0.01). Plasma NO(x) levels in group A-1 patients
      was also highest among the different groups (P < 0.01). There were no significant
      differences in intracellular NO and plasma NO(x) among group A-2, B, and C
      subjects (P > 0.05). A significant correlation between plasma NO(x) and urinary
      protein excretion was found only in group A patients and not in group B patients.
      We conclude that an aberrant immune system may exist not only in T-cells but also
      in B-cells, and NO may play some role in INS.

PMID- 19153776
TI  - Salt-losing nephrogenic diabetes insipidus caused by fetal exposure to
      angiotensin receptor blocker.
AB  - The administration of angiotensin-converting enzyme inhibitors (ACEIs) or
      angiotensin type 1 receptor blockers (ARBs) to pregnant women has been reported
      to cause ACEI/ARB fetopathy, including oligohydramios, pulmonary hypoplasia,
      renal insufficiency, limb contracture, and fetal hypotension in the child. Most
      of the patients die or develop end-stage renal failure during the neonatal
      period. The long-term prognosis of renal dysfunctions of patients with ARB
      fetopathy has not been reported. We report two pediatric cases, a 6- and 2-year
      old boy, respectively, with ARB fetopathy whose renal functions were thoroughly
      evaluated after recovery from neonatal renal failure. Both patients showed (1)
      mildly decreased glomerular filtration rate, (2) no significant proximal tubular
      dysfunctions, and (3) salt-losing nephrogenic diabetes insipidus, while the
      excretion of arginine vasopressin and urine level of cyclic AMP were increased.
      The data on these two patients indicate that the administration of ARB to the
      fetus profoundly impairs the urine concentrating ability, probably due to
      papillary atrophy and the disturbed formation of the osmotic gradient in the
      medulla, which have been confirmed in neonatal rats administered with ACEIs or
      ARBs. ACEIs/ARBs must not be administered to pregnant women.

PMID- 19153777
TI  - [High utilization of health care services by fibromyalgia patients].

PMID- 19153778
TI  - Field persistence of the edible ectomycorrhizal fungus Lactarius deliciosus:
      effects of inoculation strain, initial colonization level, and site
      characteristics.
AB  - Pinus pinea plants were inoculated with different strains of the edible
      ectomycorrhizal fungus Lactarius deliciosus. The inoculated plants were
      established in six experimental plantations in two sites located in the
      Mediterranean area to determine the effect of the initial colonization level and
      the inoculated strain on fungal persistence in the field. Ectomycorrhizal root
      colonization was determined at transplantation time and monitored at different
      times from uprooted plants. Extraradical soil mycelium biomass was determined
      from soil samples by TaqMan(R) real-time polymerase chain reaction (PCR). The
      results obtained indicate that the field site played a decisive role in the
      persistence of L. deliciosus after outplanting. The initial colonization level
      and the selection of the suitable strain were also significant factors but their
      effect on the persistence and spread of L. deliciosus was conditioned by the
      physical-chemical and biotic characteristics of the plantation soil and,
      possibly, by their influence in root growth. Molecular techniques based on real
      time PCR allowed a precise quantification of extraradical mycelium of L.
      deliciosus in the field. The technique is promising for non-destructive
      assessment of fungal persistence since soil mycelium may be a good indicator of
      root colonization. However, the accuracy of the technique will ultimately depend
      on the development of appropriate soil sampling methods because of the high
      variability observed.

PMID- 19153780
TI  - Acylthiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors:
      docking studies and ligand-based CoMFA and CoMSIA analyses.
AB  - Acylthiocarbamates (ATCs) have been identified as a class of potent non
      nucleoside HIV-1 reverse transcriptase (RT) inhibitors. A computational strategy
      based on molecular docking studies followed by comparative molecular fields
      analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA)
      was used to identify the most important features impacting ATC antiretroviral
      activity. The CoMSIA model proved to be the more predictive, with r(2)(ncv) =
      0.89, r(cv)(2) = 0.38, standard error of estimate (SEE) = 0.494, F = 84, and
      r(2)(pred) = 0.81. The results of these studies will be useful in designing new
      ATCs with improved potency, also against clinically relevant resistant mutants.

PMID- 19153779
TI  - Iron binding effects on the kinetic stability and unfolding energetics of a
      thermophilic phenylalanine hydroxylase from Chloroflexus aurantiacus.
AB  - The effects of non-heme iron binding on the function, structure, and stability of
      a monomeric phenylalanine hydroxylase from the thermophile Chloroflexus
      aurantiacus (caPAH) were investigated. Comparative studies on holo (iron-bound)
      and apo (iron-depleted) caPAH indicated that iron(II) binding does not
      significantly affect the overall structure of the enzyme. Thermal denaturation
      studies performed using differential scanning calorimetry showed that the
      unfolding reaction was kinetically controlled and that holo-caPAH displayed a
      large increase in thermal stability (approximately 15 degrees C upshift in the T
      (m) value) compared with the apoenzyme. Analysis using a simple irreversible two
      state model also showed a higher kinetic stability for holo-caPAH at optimal
      growth temperature (denaturing approximately 8 times more slowly than the apo
      form at 55 degrees C). Experiments performed in the presence of urea in
      combination with structure-energetics calculations suggest that iron binding
      reduces the change in accessible surface area exposed in the unfolding transition
      state (from approximately 36% to approximately 5% of the total change in
      accessible surface area) and also the surface involved in water-unsatisfied
      broken internal contacts (solvation barriers). Additional comparative analyses
      using phenylalanine hydroxylase from mesophilic and psychrophilic organisms
      suggest that, in addition to its catalytic role, the non-heme iron serves to
      enhance the kinetic stability of phenylalanine hydroxylase at the optimal growth
      temperature of the organism.

PMID- 19153781
TI  - De(side chain) model of epothilone: bioconformer interconversions DFT study.
AB  - Using ab initio methods, we have studied conformations of the
      de(sidechain)de(dioxy)difluoroepothilone model to quantify the effect of
      stability change between the exo and endo conformers of the epoxy ring. The DFT
      minimization of the macrolactone ring reveals four low energy conformers,
      although MP2 predicted five stable structures. The model tested with DFT hybride
      functional (B3LYP/6-31+G(d,p)) exhibits the global minimum for one of the exo
      forms (C), experimentally observed in the solid state, but unexpectedly with the
      MP2 electron correlation method for the virtual endo form (W). Using the QST3
      technique, several pathways were found for the conversion of the low energy
      conformers to the other low energy exo representatives, as well as within the
      endo analog subset. The potential energy relationships obtained for several exo
      forms suggest a high conformational mobility between three, experimentally
      observed, conformers. The high rotational barrier, however, excludes direct
      equilibrium with experimental EC-derived endo form S. The highest calculated
      transition state for the conversion of the most stable exo M interligand to the
      endo S form is approximately a 28 kcal/mol above the energy of the former. The
      two-step interconversion of the exo H conformer to the endo S requires at least
      28 kcal/mol. Surprisingly, we found that the transition state energy of the H
      form to the virtual endo W has the acceptable value of about 9 kcal/mol and the
      next energy barrier for free interconversion of endo W to endo S is 13 kcal/mol.

PMID- 19153782
TI  - Familial hemiplegic migraine: linkage to chromosome 14q32 in a Spanish kindred.
AB  - We sought to map the disease-causing gene in a large Spanish kindred with
      familial hemiplegic migraine (FHM). Patients were classified according to the
      ICHD-II criteria. After ruling out linkage to known migraine genetic loci, a
      single nucleotide polymorphism-based, 0.62-cM density genome-wide scan was
      performed. Among 13 affected subjects, FHM was the prevailing migraine phenotype
      in six, migraine with aura in four and migraine without aura in three. Linkage
      analysis revealed a disease locus in a 4.15-Mb region on 14q32 with a maximum two
      point logarithm of odds (LOD) score of 3.1 and a multipoint parametric LOD score
      of 3.8. This genomic region does not overlap with the reported migraine loci on
      14q21-22. Sequence analysis of three candidate genes in the region, SLC24A4,
      ATXN3 and ITPK1, failed to show disease-causing mutations in our patients.
      Genetic heterogeneity in FHM may be greater than previously suspected.

PMID- 19153783
TI  - Invasive Streptococcus pneumoniae infections in children and older adults in the
      north of Spain before and after the introduction of the heptavalent pneumococcal
      conjugate vaccine.
AB  - In the last two decades, an increasing trend in the incidence of pneumococcal
      disease in Europe has been reported. We investigated the effect of the use of the
      heptavalent pneumococcal conjugate vaccine (PCV7) in an area of northern Spain,
      where all recorded cases of invasive pneumococcal diseases (IPD) were included (n
      = 450; 91 between 1996-2007 in children aged <5 years and 359 between 1998-2007
      in adults aged >64 years). All isolates were serotyped. In children, the overall
      IPD incidence did not significantly decrease after the introduction, in late
      2001, of PCV7. However, the incidence of PCV7 serotypes significantly decreased
      by 137.2% from 31.59 cases/100,000 population in 1996-2001 to 13.42 in 2002-2007
      (95% confidence interval [CI] -27.2 to -342.4%), as did the overall rates of
      penicillin resistance (from 45.6 to 18.6%) and multiresistance (from 30.3 to
      11%). In older adults, the overall IPD incidence showed a non-significant
      increase due to non-PCV7 serotypes, which seemed to continue a previous trend in
      our region.

PMID- 19153786
TI  - Bacterial intein-like domains of predatory bacteria: a new domain type
      characterized in Bdellovibrio bacteriovorus.
AB  - We report a new family of bacterial intein-like domains (BILs) identified in ten
      proteins of four diverse predatory bacteria. BILs belong to the HINT
      (Hedgehog/Intein) superfamily of domains that post-translationally self-process
      their protein molecules by protein splicing and self-cleavage. The new, C-type,
      BILs appear with other domains, including putative predator-specific domain 1
      (PPS-1), a new domain typically appearing immediately upstream of C-type BILs.
      The Bd2400 protein of the obligate predator Bdellovibrio bacteriovorus includes a
      C-type BIL and a PPS-1 domains at its C-terminal part, and a signal peptide and
      two polycystic kidney disease domains at its N-terminal part. We demonstrate the
      in vivo transcription, translation, secretion, and processing of the B.
      bacteriovorus protein, and the in vitro autocatalytic N-terminal cleavage
      activity of its C-type BIL. Interestingly, whereas the Bd2400 gene is
      constitutively expressed, its protein product is differentially processed
      throughout the dimorphic life cycle of the B. bacteriovorus predator. The modular
      structure of the protein, its localization, and complex processing suggest that
      it may be involved in the interaction between the predator and its prey.

PMID- 19153788
TI  - [Prescription tip: prescribing using the motto "More helps more"].

PMID- 19153787
TI  - In vivo comparison of atherosclerotic plaque progression with vessel wall strain
      and blood flow velocity in apoE(-/-) mice with MR microscopy at 17.6 T.
AB  - OBJECT: At present, in vivo plaque characterization in mice by MRI is typically
      limited to the visualization of vascular lesions with no accompanying analysis of
      vessel wall function. The aim of this study was to analyze the influence of
      atherosclerotic plaque development on the morphological and mechanical
      characteristics of the aortic vessel wall in a pre-clinical murine model of
      atherosclerosis. MATERIALS AND METHODS: Groups of apolipoprotein E-deficient
      (apoE(-/-)) and C57BL/6J control mice fed a high-fat diet were monitored over a
      12-week time period by high-field MRI. Multi-Slice-Multi-Spin-Echo and Phase
      Contrast MRI sequences were employed to track changes to aortic vessel wall area,
      blood flow velocity and distensibility. RESULTS: After 6- and 12-weeks,
      significant changes in vessel wall area and circumferential strain were detected
      in the apoE(-/-) mice relative to the control animals. Blood flow velocity and
      intravascular lumen remained unchanged in both groups, findings that are in
      agreement with the theory of positive remodeling of the ascending aorta during
      plaque progression. CONCLUSION: This study has demonstrated the application of
      high-field MRI for characterizing the temporal progression of morphological and
      mechanical changes to murine aortic vasculature associated with atherosclerotic
      lesion development.

PMID- 19153789
TI  - [Allergic contact dermatitis].

PMID- 19153790
TI  - Exceptional LINE density at V1R loci: the Lyon repeat hypothesis revisited on
      autosomes.
AB  - The mammalian olfactory system utilizes three large receptor families: the
      olfactory receptors (ORs) of the main nose and the vomeronasal type-1 and type-2
      receptor genes (V1Rs and V2Rs) of the vomeronasal organ. We find that these loci
      are among the most long interspersed nuclear element (LINE)-dense regions of
      mammalian genomes. We investigate two evolutionary models to account for this
      cohabitation. First, we investigate an adaptive selection model, in which LINEs
      have contributed to expansions of mouse V1R repertoires. We find that even
      evolutionarily stable V1R loci are exceptionally LINE-rich compared to other
      genome loci, including loci containing other large gene clusters. Also, a more
      detailed analysis of specific V1R duplications does not reveal LINE patterns
      predicted by common LINE-mediated duplication mechanisms. Next, we investigate
      neutral models, in which LINEs were tolerated by, but not advantageous for,
      surrounding V1R genes. We find that V1R loci are exceptionally LINE-rich compared
      to other regions of similar AT base composition, and that duplicated V1R gene
      blocks are generally depleted of LINE elements, suggesting that these loci did
      not become densely populated with LINEs simply as a consequence of targeted
      integration or passive multiplication along with the genes. Finally, we show that
      individual LINE repeats of a given age at V1R, V2R, and OR loci exhibit a
      significantly longer average length than at other autosomal loci, suggesting a
      reduced tendency for these LINEs to be disrupted. We speculate that LINEs at V1R,
      V2R, and OR loci might be selectively retained because they contribute to allelic
      regulation of these three gene families.

PMID- 19153791
TI  - Genotoxic and mutagenic potential of agricultural soil irrigated with tannery
      effluents at Jajmau (Kanpur), India.
AB  - It is a common practice in India to irrigate agricultural fields with wastewater
      originating from industries and domestic sources. At Jajmau (Kanpur), India,
      tannery effluent is used for irrigation purposes. This practice has been
      polluting the soil directly and groundwater and food crops indirectly. This study
      is aimed at evaluating the mutagenic impact of soil irrigated with tannery
      effluent. Soil extracts were prepared using four organic solvents
      (dichloromethane, methanol, acetonitrile, and acetone) and tested with Ames
      Salmonella/microsome test and DNA repair-defective E. coli k-12 mutants. Gas
      Chromatography-mass spectrometric analysis of soil samples revealed the presence
      of a large number of organic compounds including bis(2-ethylhexyl)phthalate,
      benzene, 1,3-hexadien-5-yne, 2,4-bis(1,1-dimethyl)phenol, Docosane, 10
      methylnonadecane, and many higher alkanes. The soil extracts exhibited
      significant mutagenicity with Ames tester strains. TA98 was found to be the most
      sensitive strains to all the soil extracts, producing maximum response in terms
      of mutagenic index of 14.2 (-S9) and 13.6 (+S9) in the presence of
      dichloromethane extract. Dichloromethane-extracted soil exhibited a maximum
      mutagenic potential of 17.3 (-S9) and 20.0 (+S9) revertants/mg soil equivalent in
      TA100. Methanol, acetonitrile, and acetone extracts were also found to be
      mutagenic. A significant decline in the survival of DNA repair-defective E. coli
      K-12 mutants was observed compared to their isogenic wild-type counterparts when
      treated with different soil extracts. PolA mutant was found to be the most
      sensitive strain toward all four soil extracts.

PMID- 19153792
TI  - Epistasis between QTLs for bone density variation in Copenhagen x dark agouti F2
      rats.
AB  - The variation in several of the risk factors for osteoporotic fracture, including
      bone mineral density (BMD), has been shown to be strongly influenced by genetic
      differences. However, the genetic architecture of BMD is complex in both humans
      and in model organisms. We previously reported quantitative trait locus (QTL)
      results for BMD from a genome screen of 828 F2 progeny of Copenhagen and dark
      agouti rats. These progeny also provide an excellent opportunity to search for
      epistatic effects, or interaction between genetic loci, that contribute to
      fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed
      along with weight-adjusted bone density (DXA and pQCT) phenotypic data using the
      R/qtl software package. Genotype and phenotype data were permuted to determine
      genome-wide significance thresholds for the full model and epistasis
      (interaction) LOD scores corresponding to an alpha level of 0.01. A novel locus
      on chromosome 15 and a previously reported chromosome 14 QTL demonstrated a
      strong epistatic effect on BMD at the femur by DXA (LOD = 5.4). Two novel QTLs on
      chromosomes 2 and 12 were found to interact to affect total BMD at the femur
      midshaft by pQCT (LOD = 5.0). These results provide new information regarding the
      mode of action of previously identified QTL in the rat, as well as identifying
      novel loci that act in combination with known QTL or with other novel loci to
      contribute to BMD variation.

PMID- 19153793
TI  - Enriching rotifers with "premium" microalgae. Nannochloropsis gaditana.
AB  - The nutritive quality of Nannochloropsis gaditana cultured semicontinuously with
      different daily renewal rates was tested as a diet for short-term enrichment of
      the rotifer Brachionus plicatilis. After 24 h, dramatic differences in the
      survival, dry weight, and biochemical composition of the rotifers depending on
      the renewal rate of microalgal cultures were observed. Survival after the feeding
      period increased with increasing renewal rates. Rotifers fed microalgae from low
      renewal rate, nutrient-deficient cultures showed low dry weight and organic
      contents very similar to those of the initial rotifers that were starved for 12 h
      before the start of the feeding period. On the contrary, rotifers fed nutrient
      sufficient microalgal cells underwent up to twofold increases of dry weight and
      protein, lipid, and carbohydrate contents with regard to rotifers fed nutrient
      depleted N. gaditana. Consequently, feed conversion rate decreased in these
      conditions, indicating a better assimilation of the microalgal biomass obtained
      at high renewal rates. No single microalgal biochemical parameter among those
      studied can explain the response of the filter feeder. Similarly to gross
      composition, EPA and n-3 contents in rotifers fed microalgae from nutrient
      sufficient cultures were double than the contents found in rotifers fed nutrient
      limited microalgae. In addition, very high positive correlations between the
      contents of EPA and n-3 in N. gaditana and B. plicatilis were observed. These
      results demonstrate that selecting the appropriate conditions of semicontinuous
      culture can strongly enhance the nutritional value of microalgae that is
      reflected in the growth and biochemical composition of the filter-feeder even in
      short exposure periods.

PMID- 19153794
TI  - Visualization of phosphoinositides via the development of the transient
      expression system of a cyan fluorescent protein in the red alga Porphyra
      yezoensis.
AB  - Phosphoinositides (PIs) play important roles in signal transduction pathways and
      the regulation of cytoskeleton and membrane functions in eukaryotes. Subcellular
      localization of individual PI derivative is successfully visualized in yeast,
      animal, and green plant cells using PI derivative-specific pleckstrin homology
      (PH) domains fused with a variety of fluorescent proteins; however, expression of
      fluorescent proteins has not yet been reported in any red algal cells. In the
      present study, we developed the system to visualize these PIs using human PH
      domains fused with a humanized cyan fluorescent protein (AmCFP) in the red alga
      Porphyra yezoensis. Plasma membrane localization of AmCFP fused with the PH
      domain from phospholipase Cdelta1 and Akt1, but not Bruton's tyrosine kinase, was
      observed in cell wall-free monospores, demonstrating the presence of
      phosphatidylinositol-4,5-bisphosphate and phosphatidylinositol-3,4-bisphosphate
      in P. yezoensis cells. This is the first report of the successful expression of
      fluorescent protein and the monitoring of PI derivatives in red algal cells. Our
      system, based on transient expression of AmCFP, could be applicable for the
      analysis of subcellular localization of other proteins in P. yezoensis and other
      red algal cells.

PMID- 19153795
TI  - Caterpillar footprints as host location kairomones for Cotesia marginiventris:
      persistence and chemical nature.
AB  - Herbivores walking over the epicuticular wax layer of a plant may leave tracks
      that disclose their presence to hunting predators or parasitoids. The braconid
      wasp Cotesia marginiventris is a solitary parasitoid of young noctuid
      caterpillars. It can locate potential hosts from a distance by orienting toward
      the scent of herbivore-damaged plants. Upon landing on the caterpillars' food
      plant, the female parasitoid searches for further cues (kairomones) that confirm
      the presence of a suitable host. In a previous study, we showed that C.
      marginiventris recognizes the chemical footprints of absent Spodoptera frugiperda
      caterpillars on a leaf. Here, we report on the persistence and chemical nature of
      this host location kairomone. In a series of behavioral assays, we confirmed that
      caterpillars of S. frugiperda leave chemical tracks that elicit characteristic
      antennation behavior in C. marginiventris for up to 2 days. Both hexane extracts
      of caterpillar footprints and of the larvae's ventral cuticle induced antennation
      and contained almost identical long-chain hydrocarbons, thus suggesting the
      prolegs and claspers as the kairomones' main source. A series of linear C(21) to
      C(32) alkanes accounted for ca 90% of all identified compounds. Female wasps
      showed significant antennation responses on leaves treated with a reconstructed
      blend of these n-alkanes. However, wasp responses were relatively weak.
      Therefore, we presume that minor compounds, such as monomethyl-branched alkanes,
      which were also found, may contribute additionally to host recognition.

PMID- 19153796
TI  - Is (-)-catechin a novel weapon of spotted knapweed (Centaurea stoebe)?
AB  - The novel weapons hypothesis states that some invasive weed species owe part of
      their success as invaders to allelopathy mediated by allelochemicals that are new
      to the native species. Presumably, no resistance has evolved among the native
      species to this new allelochemical (i.e., the novel weapon). In their native
      habitat, however, the plants that co-evolved with these invasive species have
      theoretically evolved defenses that obviate the allelochemical advantage.
      Previous studies have claimed that catechin is such a novel weapon of spotted
      knapweed (Centaurea stoebe = C. maculosa), an invasive species in the non-native
      habitat of North America. These studies indicated that (-)-catechin is more
      phytotoxic than (+)-catechin. Other studies have not found sufficient catechin in
      field soils to support this theory. We report that (-)-catechin and (+)-catechin
      are essentially equal, but poorly phytotoxic to a variety of plant species in
      bioassays without soil. In a dose/response experiment with Montana soils, we
      found the lowest dose for a growth reduction of two native Montana grasses
      (Koeleria macrantha and Festuca idahoensis) by a racemic mixture of (+/-)
      catechin that ranged from about 25 to 50 mM, concentrations, orders of magnitude
      higher than expected in nature. Autoclaving the soil before adding the catechin
      did not affect the activity of catechin. We found (-)-catechin to be a potent
      antioxidant, in contrast to a previous claim that it acts as an allelochemical by
      causing oxidative stress. Our findings suggest that catechin is not a novel
      weapon of spotted knapweed and that other allelochemical(s) or alternative
      mechanisms must be found to explain the success of this species as an invader in
      North America.

PMID- 19153797
TI  - Assessment of the allelopathic potential of Juniperus ashei on germination and
      growth of Bouteloua curtipendula.
AB  - Potential allelopathic compounds of Juniperus ashei Buchh. (Ashe juniper) and
      their effect on a native grass were determined in laboratory and field studies.
      Solid-phase microextraction and gas chromatography/mass spectrometry were used to
      determine if monoterpenes found in the essential oils of J. ashei are released in
      leaf and litter leachate, as well as volatilized from leaf tissue. Camphor,
      bornyl acetate, and limonene were found in leaf and fresh litter leachates;
      however, degraded litter did not contain any of these compounds. Camphor was the
      most common potentially allelopathic compound found in J. ashei leaf and litter
      leachate and in volatiles from leaf tissue. The effects of leaf and litter tissue
      on the germination of Bouteloua curtipendula (Michx.) Torr. (side-oats grama) was
      tested by using the "sandwich agar method". The highest germination of B.
      curtipendula (29.6%) occurred in the control, which was significantly higher than
      fresh litter (13.2%) and degraded litter (16.2%). The lowest germination (6.2%)
      occurred with J. ashei leaves. In the field experiment, aboveground dry mass of
      B. curtipendula was evaluated in relation to position within the canopy and
      intercanopy of J. ashei adult trees when light and water were held constant
      across locations. Aboveground dry mass of B. curtipendula was significantly
      greater in the intercanopies of J. ashei (163.7 g m(2)) compared to the dry mass
      in the understory (44.8 g m(2)) and dripline (44.5 g m(2)), suggesting some
      negative influence by J. ashei. Chemical analyses indicate that monoterpenes are
      released through leaching and volatilization from J. ashei, and germination and
      field studies suggest that these compounds inhibit B. curtipendula.

PMID- 19153798
TI  - Behavioral evidence for a contact sex pheromone component of the emerald ash
      borer, Agrilus planipennis Fairmaire.
AB  - The cuticular hydrocarbon profiles of emerald ash borers, Agrilus planipennis,
      were examined to determine if there are differences in these compounds between
      the sexes. We also assessed feral male EAB in the field for behavioral changes
      based on the application of a female-specific compound to dead, solvent-washed
      beetles. Males in the field spent significantly more time attempting copulation
      with dead, pinned female beetles coated with a three-beetle-equivalent dose of 3
      methyltricosane than with solvent-washed beetles or those coated in 3
      methyltricosane at lower concentrations. Males in the field spent the most time
      investigating pinned dead, unwashed female beetles. In the laboratory, sexually
      mature males were presented with one of several mixtures applied in hexane to
      filter paper disks or to the elytra of dead female beetles first washed in
      solvent. Male EAB also spent more time investigating dead beetles treated with
      solution applications that contained 3-methyltricosane than dead beetles and
      filter paper disks treated with male body wash or a straight-chain hydrocarbon
      not found on the cuticle of EAB.

PMID- 19153799
TI  - Detection and discrimination of mixed odor strands in overlapping plumes using an
      insect-antenna-based chemosensor system.
AB  - Olfactory signals, a major means of communication in insects, travel in the form
      of turbulent odor plumes. In terrestrial environments, an odor blend emitted from
      a single point source exists in every strand of the plume, whereas, in confluent
      plumes from two different odor sources, the strands have some chance of being
      coincident and comprising a new third odor in those strands. Insects have the
      ability to detect and interpret necessary olfactory information from individual
      filamentous odor strands in complex multifilament odor plumes. However,
      behaviorists have had no way to measure the stimulus situations they are
      presenting to their temporally acute insect subjects when performing Y-tube
      olfactometer or confluent pheromone plume wind tunnel assays. We have
      successfully measured the degree of plume-strand mixing in confluent plumes in a
      wind tunnel by using a multichannel insect-antenna-based chemosensor. A PC-based
      computer algorithm to analyze antennal signals from the probe portion of the
      system performed real-time signal processing and, following a short training
      session, classified individual odorant/mixture strands at sub-second temporal
      resolution and a few tens of millimeters of spatial resolution. In our studies,
      the chemosensor classified a higher frequency of strands of two different
      odorants emitted from two closely spaced filter papers as being "mixed" when the
      sources were located only 1 or 2 cm apart than when the sources were 5 or 10 cm
      apart. These experiments demonstrate the chemosensor's potential to be used for
      measuring odor stimulus situations in more complex multiple-plume environments.

PMID- 19153800
TI  - Integrating psychology within the globalizing world: a requiem to the post
      modernist experiment with Wissenschaft.
AB  - Since the new beginning in 2007 of Integrative Psychological & Behavioral Science
      we have brought out to the open both the reasons why the ever-widening research
      enterprise in psychology has largely failed to produce general knowledge, and to
      point to promising new directions in the field. The post-modernist turn in
      psychology is now over, and it is an interesting task to return to creating a
      universal science of psychology that is context-sensitive, and culture-inclusive.
      The latter goal entails a renewed focus upon qualitative analyses of time-based
      processes, close attention to the phenomena under study, and systematic (single
      system-based-usually labeled idiographic) focus in empirical investigations.
      Through these three pathways centrality of human experiencing of culturally
      constructed worlds is restored as the core of psychological science. Universal
      principles are evident in each and every single case. Transcending post-modernist
      deconstruction of science happens through active international participation and
      a renewed focus on creating general theories. Contemporary psychology is global
      in ways that no longer can any country's socio-political world view dominate the
      field. Such international equality of contributions grants innovation of the core
      of the discipline, and safeguards it against assuming any single cultural myth
      story as the axiomatic basis for the discipline.

PMID- 19153801
TI  - Bacterial diversity in surface sediments from the Pacific Arctic Ocean.
AB  - In order to assess bacterial diversity within four surface sediment samples (0-5
      cm) collected from the Pacific Arctic Ocean, 16S ribosomal DNA clone library
      analysis was performed. Near full length 16S rDNA sequences were obtained for 463
      clones from four libraries and 13 distinct major lineages of Bacteria were
      identified (alpha, beta, gamma, delta and epsilon-Proteobacteria, Acidobacteria,
      Bacteroidetes, Chloroflexi, Actinobacteria, Firmicutes, Planctomycetes,
      Spirochetes, and Verrucomicrobia). alpha, gamma, and delta-Proteobacteria,
      Acidobacteria, Bacteroidetes, Actinobacteria were common phylogenetic groups from
      all the sediments. The gamma-Proteobacteria were the dominant bacterial lineage,
      representing near or over 50% of the clones. Over 35% of gamma-Proteobacteria
      clones of four clone library were closely related to cultured bacterial isolates
      with similarity values ranging from 94 to 100%. The community composition was
      different among sampling sites, which potentially was related to geochemical
      differences.

PMID- 19153802
TI  - Chronic diarrhea caused by Hymenolepis nana in a renal transplant recipient.

PMID- 19153803
TI  - Autonomic neuropathy in hemodialysis patients: questionnaires versus clinical
      tests.
AB  - AIM: Uremic neuropathy (UN) is a typical complication of long-term dialysis
      therapy and may manifest as distal, symmetric, and both senso-motoric and
      autonomic nerve dysfunction. Its clinical picture is highly variable and it is
      not known how the symptoms of UN reported by chronic dialysis patients correspond
      to positive results of clinical tests for autonomic dysfunction. The objective of
      this study was to compare the prevalence of self-reported symptoms of autonomic
      neuropathy (AN) revealed in patient questionnaires with the prevalence of
      findings from objective clinical tests. METHODS: The study group included 45
      patients (26 males, 19 females), mean age 60 +/- 15.5 years, on chronic
      hemodialysis for 7.8 +/- 2.6 years. In all subjects, blood pressure (BPci) and
      heart rate (HRci) variability indexes (calculated as BP and HR during Ewing and
      Clarke' tests divided by HR and BP at rest) were measured using the Finapres
      which records beat-to-beat blood pressure and heart rate. Additionally, patients
      completed seven-question questionnaires which assessed the presence of most
      typical AN symptoms. The control group comprised 12 healthy subjects (age 52 +/-
      19.5 years). RESULTS: The results from the questionnaires showed that falls of BP
      occurred in 73% of patients, itching of skin in 42%, constipation or diarrhea in
      33%, filling of stomach in 25%, and decreased sweating in 17%. Altogether 85.9%
      of patients reported one or more subjective symptoms of neuropathy. In contrast,
      modified Ewing and Clarke's test revealed that only 17.7% of participants
      demonstrated overt pathologies. Neither blood pressure nor heart rate
      changeability indexes in patients and healthy subjects showed significant
      differences with the exception of intense inhalation and static effort.
      CONCLUSIONS: Our results show much higher frequency of subjective symptoms of AN
      in chronic dialysis patients than objective symptoms detected with clinical
      tests.

PMID- 19153804
TI  - Hemolytic anemia after ABO nonidentical living donor kidney transplantation.
AB  - INTRODUCTION: ABO compatible non-identical kidney transplants are used
      frequently. Acquired hemolytic anemia has been reported after ABO mismatched
      transplantation. Patients of A, B or AB blood groups may receive organs from ABO
      compatible, but non-identical donors, mostly from O blood group donors. It may
      also occur in patients of the AB blood group who receive a kidney from a donor of
      the A or B blood groups. PATIENTS AND METHODS: ABO non-identical living donor
      kidney transplantation was done in 214 cases. All studied patients received
      kidneys from one haplotype HLA mismatched living donors and had pretransplant non
      specific blood transfusions. There were 164 males and 50 females with a mean age
      of 30 years. Ten patients with cyclosporine (CsA)-based therapy developed
      hemolysis. CsA was stopped in patients maintained on triple immunosuppression
      (pred, CsA, AZA) and shifted to azathioprine in patients maintained on pred CsA
      therapy. In all patients pretransplant antibody screen, direct antiglobulin test
      (DAT) and cytotoxic cross match were all negative. RESULTS: The prognosis was
      excellent in nine patients, and one died from severe hemolysis. Hemolytic anemia
      was more frequent among blood group A recipients (60% of our cases) and more
      severe among recipient blood group B. Six patients received antigen-negative
      packed RBCs. Univariate analysis demonstrated significant impact for recipient
      age, donor sex, number of pretransplant blood transfusions, primary
      immunosuppression, time to onset of diuresis, recipient and donor blood groups.
      Multivariate analysis restricted the significance to blood group of donor and
      recipient, time to onset of diuresis and primary immunosuppression. CONCLUSIONS:
      Post transplant hemolysis is infrequent after renal transplantation; however, it
      may occur with compatible, non-identical ABO blood group donors. Blood group of
      donor and recipient, time to onset of diuresis and primary immunosuppression
      (mainly CsA) were significant risk factors in hemolytic anemia in patients after
      ABO non-identical living donor kidney transplantation. The condition is usually
      mild and self limited, and change of immunosuppression (stop CsA) can treat the
      condition.

PMID- 19153805
TI  - Nocturnal hemodialysis.
AB  - With the increasing number of patients with end stage renal disease comes an
      increasingly urgent need for renal replacement therapy that is both clinically
      effective and cost effective. This article explores some of the advantages of
      nocturnal hemodialysis as well as some of the barriers to its use.

PMID- 19153807
TI  - Resin glycosides from the leaves and stems of Ipomoea digitata.
AB  - Alkaline hydrolysis of the ether-soluble resin glycoside (jalapin) fraction of
      the leaves and stems of Ipomoea digitata L. (Convolvulaceae) gave six organic
      acids, isobutyric, (S)-2-methylbutyric, tiglic, n-decanoic, n-dodecanoic, and
      cinnamic acids, and two glycosidic acids, quamoclinic acid A and operculinic acid
      A. Further, a new genuine resin glycoside, named digitatajalapin I, was isolated
      from the jalapin fraction, along with three known resin glycosides. Their
      structures have been determined on the basis of chemical and spectroscopic data.

PMID- 19153806
TI  - A comparative psychophysical approach to visual perception in primates.
AB  - Studies on the visual processing of primates, which have well developed visual
      systems, provide essential information about the perceptual bases of their higher
      order cognitive abilities. Although the mechanisms underlying visual processing
      are largely shared between human and nonhuman primates, differences have also
      been reported. In this article, we review psychophysical investigations comparing
      the basic visual processing that operates in human and nonhuman species, and
      discuss the future contributions potentially deriving from such comparative
      psychophysical approaches to primate minds.

PMID- 19153808
TI  - Scoring confidence index: statistical evaluation of ligand binding mode
      predictions.
AB  - Protein-ligand docking programs can generate a large number of possible binding
      orientations for each ligand candidate. The challenge is to identify the
      orientations closest to the native binding mode using a scoring method. Many
      different scoring functions have been developed for protein-ligand scoring, but
      their performance on binding mode prediction is often target-dependent. In this
      study, a statistical approach was employed to provide a confidence measure of
      scoring performance in finding close to the correct docked ligand orientations.
      It exploits the fact that the scores provided by an adequately performing scoring
      function generally improve as the ligand binding modes get closer to the correct
      native orientation. For such cases, the correlation coefficient of scores versus
      distances is expected to be highest when the most native-like orientation is used
      as a reference. This correlation coefficient, called the correlation-based score
      (CBScore), was used as an indicator of how far the docked pose was from the
      native orientation. The correlation between the original scores and CBScores as
      well as the range of CBScores were found to be good measures of scoring
      performance. They were combined into a single quantity, called the scoring
      confidence index. High values of the scoring confidence index were indicative of
      pronounced and relatively smooth binding energy landscapes with easily
      discernable global minima, resulting in reliable binding mode predictions. Low
      values of this index reflected rugged energy landscapes making the prediction of
      the correct binding mode very difficult and often unreliable. The diagnostic
      ability of the scoring confidence index was tested on a non-redundant set of 50
      protein-ligand complexes scored with three commonly employed scoring functions:
      AffiScore, DrugScore and X-Score. Binding mode predictions were found to be three
      times more reliable for complexes with scoring confidence indices in the upper
      half than for cases with values in the lower half of the resulting range of 0
      1.6. This new confidence measure of scoring performance is expected to be a
      valuable tool for virtual screening applications.

PMID- 19153809
TI  - Structure-function relationships in the bifunctional ferrisiderophore FpvA
      receptor from Pseudomonas aeruginosa.
AB  - FpvA is the primary outer membrane transporter required for iron acquisition via
      the siderophore pyoverdine (Pvd) in Pseudomonas aeruginosa. FpvA, like other
      ferrisiderophore transporters, consists of a membrane-spanning beta-barrel
      occluded by a plug domain. The beta-strands of the barrel are connected by large
      extracellular loops and periplasmic turns. Like some other TonB-dependent
      transporters, FpvA has a periplasmic domain involved in a signalling cascade that
      regulates expression of genes required for ferrisiderophore transport. Here, the
      structures of FpvA in different loading states are analysed in light of
      mutagenesis data. This analysis highlights the roles of different protein domains
      in Pvd-Fe uptake and the signalling cascade and reveals a strong correlation
      between Pvd-Fe transport and activation of the signalling cascade. It is likely
      that conclusions drawn for FpvA will be relevant to other TonB-dependent
      ferrisiderophore transport and signalling proteins.

PMID- 19153810
TI  - Genetic changes in plant growth and their associations with chromosomes from
      Gossypium barbadense L. in G. hirsutum L.
AB  - Cotton (Gossypium spp.) plant growth is an important time-specific agronomic
      character that supports the development of squares, flowers, boll retention, and
      yield. With the use of a mixed linear model approach, we investigated 14 cotton
      chromosome substitution (CS-B) lines and their chromosome-specific F(2) hybrids
      for genetic changes in plant growth that was measured during the primary
      flowering time under two environments. The changes in additive and dominance
      variances for plant height and number of mainstem nodes are reported, showing
      that additive effects for these two traits were a key genetic component after
      initial flowering occurred in the field. Time-specific genetic variance
      components were also detected where phenotypic values observed at time t were
      conditioned on the events occurring at time t - 1, demonstrating new genetic
      variations arising at several time intervals during plant growth. Results also
      revealed that plant height and number of nodes shared some common influence due
      to additive effects during plant development. With the comparative analyzes,
      chromosomes associated with the genetic changes in plant growth were detected.
      Therefore, these results should add new understanding of the genetics underlying
      these time-specific traits.

PMID- 19153811
TI  - Microbial populations related to PAH biodegradation in an aged biostimulated
      creosote-contaminated soil.
AB  - A previous bioremediation survey on a creosote-contaminated soil showed that
      aeration and optimal humidity promoted depletion of three-ringed polycyclic
      aromatic hydrocarbons (PAHs), but residual concentrations of four-ringed
      benzo(a)anthracene (B(a)A) and chrysene (Chry) remained. In order to explain the
      lack of further degradation of heavier PAHs such as four-ringed PAHs and to
      analyze the microbial population responsible for PAH biodegradation, a chemical
      and microbial molecular approach was used. Using a slurry incubation strategy,
      soil in liquid mineral medium with and without additional B(a)A and Chry was
      found to contain a powerful PAH-degrading microbial community that eliminated 89%
      and 53% of the added B(a)A and Chry, respectively. It is hypothesized that the
      lack of PAH bioavailability hampered their further biodegradation in the unspiked
      soil. According to the results of the culture-dependent and independent
      techniques Mycobacterium parmense, Pseudomonas mexicana, and Sphingobacterials
      group could control B(a)A and Chry degradation in combination with several
      microorganisms with secondary metabolic activity.

PMID- 19153812
TI  - Effect of fungal infection on reproductive potential and survival time of
      Tetranychus urticae (Acari: Tetranychidae).
AB  - The effect of fungal infection on the reproductive potential of two-spotted
      spider mite, Tetranychus urticae, was evaluated as part of the full biocontrol
      potential of three entomopathogenic fungi by modeling of fecundity probability.
      Female mites (<or=2-day-old) on leaves were exposed to the sprays of Beauveria
      bassiana, Paecilomyces fumosoroseus and Metarhizium anisopliae at the
      concentrations of 1.13 x 10(3), 1.55 x 10(3) and 0.95 x 10(3) deposited conidia
      mm(-2) and then individually reared at 25 degrees C and 12:12 L:D for
      oviposition. Mite mortalities 10 days after spraying were 73.1, 75.4 and 67.9% in
      the fungal treatments versus 15.5% in control. On average, females infected by
      the three fungal species survived 5.8, 6.2 and 6.3 days, and laid 3.1, 4.0 and
      4.0 eggs per capita, respectively. These were 3-4 fold lower than the control
      fecundity at 12.3. The cumulative probabilities [P(m <or= N)] for the counts of
      infected and non-infected (control) females laying m eggs per capita (m <or= N)
      during 10 days fit very well the equation P(m <or= N) = 1/[1 + exp(a + bm)] (r(2)
      >or= 0.98), yielding a solution to the probability for the female mites to
      achieve a specific fecundity {P(m <or= N)-P[m <or= (N - 1)]}. Consequently, the
      infected mites had 71-78% chance to lay <or=5 eggs per capita but only 5-8% to
      deposit >10 eggs despite some variation among the tested fungi. In contrast, the
      chances for the non-infected mites to achieve the low and high fecundities were
      23 and 55%. The fitted probabilities provide a full coverage of the fecundity
      potential of infected versus non-infected mites and are more informative than the
      mean fecundities.

PMID- 19153813
TI  - Modelling the potential distribution of the invasive tomato red spider mite,
      Tetranychus evansi (Acari: Tetranychidae).
AB  - Predicting the potential geographical distribution of a species is particularly
      important for pests with strong invasive abilities. Tetranychus evansi Baker &
      Pritchard, possibly native to South America, is a spider mite pest of solanaceous
      crops. This mite is considered an invasive species in Africa and Europe. A CLIMEX
      model was developed to predict its global distribution. The model results fitted
      the known records of T. evansi except for some records in dry locations. Dryness
      as well as excess moisture stresses play important roles in limiting the spread
      of the mite in the tropics. In North America and Eurasia its potential
      distribution appears to be essentially limited by cold stress. Detailed potential
      distribution maps are provided for T. evansi in the Mediterranean Basin and in
      Japan. These two regions correspond to climatic borders for the species. Mite
      establishment in these areas can be explained by their relatively mild winters.
      The Mediterranean region is also the main area where tomato is grown in open
      fields in Europe and where the pest represents a threat. According to the model,
      the whole Mediterranean region has the potential to be extensively colonized by
      the mite. Wide expansion of the mite to new areas in Africa is also predicted.
      Agricultural issues highlighted by the modelled distribution of the pest are
      discussed.

PMID- 19153814
TI  - Dietary protein content influences both growth and size distribution of anterior
      and posterior muscle fibres in juveniles of Pagellus bogaraveo (Brunnich).
AB  - Muscle cellularity was studied in Pagellus bogaraveo juveniles fed on diets with
      different protein contents. Measured in transversal body sections, at both post
      opercular and post-anal locations, the morphometric variables estimated were:
      total muscle area (A), total number of fibres (N), number of fibres per unit area
      of muscle (N (A)) and cross-sectional fibre area (a) of the two main muscle fibre
      types. At the end of the experiment fish fed on diets having more than 40% of
      protein displayed significantly higher body weight. Fish fed on protein-rich
      diets exhibited greater a and N. For fish fed on 30 and 50% protein diets the
      morphometric parameters measured grew linearly with the fish weight. High-protein
      diets favoured muscle hyperplasia. When comparing rostral and caudal locations, a
      greater N and a smaller a of posterior red fibres were the consistent differences
      found-a fact, to our knowledge, so far unreported for fish.

PMID- 19153815
TI  - Footsteps of the European society for muscle research (1971-2008).

PMID- 19153816
TI  - Characterization of type I, III and V collagens in high-density cultured
      tenocytes by triple-immunofluorescence technique.
AB  - The purpose of this study is to examine the intracellular distribution of
      collagen types I, III and V in tenocytes using triple-label immunofluorescence
      staining technique in high-density tenocyte culture on Filter Well Inserts (FWI).
      The tenocytes were incubated for 4 weeks under monolayer conditions and for 3
      weeks on FWI. At the end of the third week of high-density culture, we observed
      tenocyte aggregation followed by macromass cluster formation. Immunofluorescence
      labeling with anti-collagen type I antibody revealed that the presence of
      collagen type I was mostly around the nucleus. Type III collagen was more
      diffused in the cytoplasm. Type V collagen was detected in fibrillar and
      vesicular forms in the cytoplasm. We conclude that, the high-density culture on
      FWI is an appropriate method for the production of tenocytes without loosing
      specialized processes such as the synthesis of different collagen molecules. We
      consider that the high-density culture system is suitable for in vitro
      applications which affect tendon biology and will improve our understanding of
      the biological behavior of tenocytes in view of adequate matrix structure
      synthesis. Such high-density cultures may serve as a model system to provide
      sufficient quantities of tenocytes to prepare tenocyte-polymer constructs for
      tissue engineering applications in tendon repair.

PMID- 19153817
TI  - Prevalence of Bovine viral diarrhoea virus (BVDV) antibodies among sheep and
      goats in India.
AB  - The aim of this study was to determine the prevalence of pestivirus antibodies in
      sheep and goats in India. A total of 2803 serum samples collected between 2004
      and 2008 from 1777 sheep in 92 flocks and 1026 goats in 63 flocks belonging to 13
      states were tested by competition ELISA for detection of pestivirus antibodies.
      In sheep, the true prevalence rate was 23.4% (95% confidence interval: 22.9%
      27.0%) and in goats it was 16.9% (95% CI: 16.4%-21.3%). The flock level
      seroprevalence was 66.3% for sheep and 54.0% for goats. Geographical variation in
      individual and flock prevalence was highly significant. A significant association
      (p < 0.05) was found between sheep and goat flocks having cattle contact and the
      flock level seroprevalence. The seroprevalence was lower in 6 months-1 year age
      group compared to the 1-2 year and >2 year age groups in both sheep and goats.
      Cross neutralization studies on 61 seropositive sheep and 34 seropositive goat
      samples representing all positive flocks, exhibited > four fold higher titre to
      bovine viral diarrhoea virus type 1 (BVDV-1) in 41 sheep and 23 goat samples and
      to BVDV-2 in one sheep and goat each. This study for the first time showed
      serological evidence of wide spread BVDV infections in Indian sheep and goats,
      with BVDV-1 predominating and BVDV-2 occasionally besides highlighting the
      potential risk of infection to other species, which needs to be considered
      whenever BVD control measures are initiated.

PMID- 19153818
TI  - Characteristics of patients using psychoactive drugs in Karachi, Pakistan.
AB  - OBJECTIVES: To assess the distribution of various characteristics related to use
      of psychoactive drugs and the differences by gender. METHOD: A case-series study
      was conducted at the out-patient clinic affiliated with a teaching hospital in
      Karachi, Pakistan. After taking consent to participate, 118 adult patients who
      visited these clinics for consultation for any reason and were taking
      psychoactive drug(s) were interviewed. RESULTS: Over 40% of the study subjects
      were taking psychoactive drugs without an advice from their doctor. In all, 78%
      were taking psychoactive drugs for >6 months and 67% were using these drugs on a
      regular basis. Over 85% were using these for induction of sleep and 59% for
      relaxation. Seventy-five percent of study participants reported that they can
      afford these pills and over 46% were able to get these drugs easily;
      significantly more men compared to women (58% vs. 39%; difference of proportion =
      -19.7; 95% CI = -37, -1.5). All other studied characteristics were equally
      distributed among men and women. CONCLUSION: In this study a substantial number
      of cases were using psychoactive drugs without doctors' advice. Patient education
      and health awareness sessions may be helpful in preventing inappropriate use of
      psychotropic drugs.

PMID- 19153820
TI  - Multidetector-row computed tomographic evaluation of myocardial perfusion in
      reperfused chronic myocardial infarction: value of color-coded perfusion map in a
      porcine model.
AB  - We aimed to develop color-coded CT perfusion maps (CPM) of infarcted myocardium
      and assess the utility of CPM in evaluating ischemic heart disease on a cardiac
      multi-detector CT (MDCT) in a porcine reperfused-myocardial-infarction model.
      Myocardial infarctions were induced by 30 min occlusions of the proximal left
      anterior descending coronary artery (LAD) in 17 healthy adult female pigs. First
      pass and 5 min-delayed cardiac MDCTs were performed after 4 weeks of LAD
      occlusion. Myocardial CPMs were obtained by using the CPM program.
      Triphenyltetrazolium chloride (TTC)-staining was performed on the cardiac
      specimens. We analyzed the intermodality agreement on the size and location of
      the myocardial infarctions. TTC staining revealed myocardial infarction in 16 of
      17 pigs, and 15 of these (94%) showed matched infarcts on the CPM and first-pass
      images. The areas of perfusion deficit noted in early arterial phase images and
      CPM coincided exactly with the areas of poor TTC staining in 12 of 15 pigs (80%).
      In the three remaining pigs, the areas of poor TTC staining were larger than
      those of a perfusion deficit demonstrated by either early arterial phase images
      or CPM. The agreement between these tests is calculated to be moderate to good (k
      = 0.736, P < 0.05). Ten myocardial segments in 4 of the 15 pigs (27%) with
      hypoattenuated myocardium showed a delayed enhancement on the 5 min-delayed
      images. Contrast-enhanced MDCT was useful and accurate in detecting chronic
      myocardial infarction; CPM was helpful in visualizing the infarcted myocardium.

PMID- 19153821
TI  - MSMEG_4626 ribonuclease from Mycobacterium smegmatis.
AB  - The MSMEG_4626 gene was cloned from Mycobacterium smegmatis MC2 155. It codes for
      a protein of 1,037 amino acids, identified as ribonuclease E by matching to the
      protein family HMM TIGR00757. The protein was expressed and purified. Although
      its calculated molecular weight is 112.7 kDa, it has an aberrant mobility in SDS
      polyacrylamide gels, like other ribonuclease E enzymes (it migrates as a 180 kDa
      protein). The central part of the protein displays high similarity to the
      catalytic domains of other RNase E enzymes. Mass spectrometric analysis revealed
      the presence of the chaperonin GroEL, ribosomal proteins, a negative regulator of
      genetic competence and GTP pyrophosphokinase in the affinity-purified
      preparation. It is a very unstable protein; despite the use of protease
      inhibitors in addition to the full-length RNase E its proteolytic fragments were
      detected.

PMID- 19153822
TI  - Consistency of self-reported first-degree family history of cancer in a
      population-based study.
AB  - The aim of this study was to assess the prevalence and consistency of self
      reported family history of cancer among first-degree relatives (FDR) in a
      population-based study. Women at primary care units (PCU) were submitted to a
      questionnaire about cancer family history. Consistency of the report was
      determined by comparing self-reported history at the PCU to data from subsequent
      genetic evaluations and/or cancer confirmatory documents. Consistency in relation
      to degree of education, reported tumor type and reported age at cancer diagnosis
      in FDR was assessed. In 8,881 women interviewed, the prevalence of cancer in an
      FDR was 25.14% (CI 95%: 24.14; 25.94). Mean age was 40.29 years and most (70.26%)
      had < or = 8 years of education. There was a good agreement of self-reported
      cancer history at the PCU and in subsequent genetic evaluations [Kappa
      coefficient = 0.76 (P < 0.05)]. Inconsistencies were not related to low literacy
      (chi (2) = 2.027; P = 0.363). Consistency of the reported information for cancer
      status, cancer type and age of onset was 92.59%, 85.33% and 92.64%, respectively.
      The prevalence of cancer history in an FDR was similar to previous reports in
      other populations. Consistency and reliability of the self-reported information
      was high, regardless of educational level.

PMID- 19153823
TI  - Composite carcinoma of the stomach associated with sarcoid-like granulomas.
AB  - Composite glandular/exocrine-endocrine carcinoma of the gastrointestinal tract is
      a special tumor type composed of common adenocarcinoma and the neuroendocrine
      component comprising at least one-third of the whole tumor area. These tumors are
      rare in the stomach and mostly published as case reports. We describe a further
      case of a 36-year-old man being unique in that it was associated with extensive
      formation of sarcoid-like granulomas. Tumor consisted of, predominantly poorly
      differentiated, intestinal-type adenocarcinoma and poorly differentiated
      neuroendocrine, small cell carcinoma. The adenocarcinomatous and neuroendocrine
      areas were separated, but closely juxtaposed with focal areas showing gradual
      transition from one to another. Perigastric lymph node metastases corresponded
      either to neuroendocrine or adenocarcinomatous component. On
      immunohistochemistry, the exocrine part was positive for cytokeratin 7, whereas
      superficial well-differentiated parts showed positivity with cytokeratin 20 as
      well. The neuroendocrine component was negative with those two types of
      cytokeratin. Both adenocarcinomatous and neuroendocrine tumor portions showed
      carcinoembryonic antigen (CEA) immunoexpression. Neuroendocrine markers
      (chromogranin A, synaptophysin and neuron-specific enolase) were diffusely
      positive in the neuroendocrine component, and found only in the scattered cells
      within the neoplastic glands of the adenocarcinoma. Entire gastric mucosa and all
      perigastric lymph nodes were extensively affected by noncaseating, sarcoid-like
      granulomas. The absence of any clinical manifestations combined with the negative
      results of chest radiograph and laboratory test for the serum angiotensin
      converting enzyme argued against the possibility of systemic sarcoidosis.

PMID- 19153824
TI  - Psychology and medical education: collaborations for culturally responsive care.
AB  - Recent years have witnessed an increasing attention to the vast and alarming
      health disparities in the United States. This paper explores provider factors in
      health disparities, considering the role of medical education in training health
      care providers to practice culturally responsive health care toward a diminution
      of health inequalities. The paper begins with a description of culturally
      responsive care along with an overview of the key elements of a comprehensive
      curriculum for health care providers in this arena. Next, the paper explores the
      key contributions from the field of psychology to collaborative instruction of
      health care providers in the areas of attitudes/awareness, knowledge and skills
      components of culturally responsive care. Finally, the paper concludes with a
      description of collaborative teaching from a family medicine residency program
      where a 33-h 'cultural medicine curriculum within the curriculum' is delivered
      over the course of 3 years.

PMID- 19153825
TI  - Molecular analysis of duck enteritis virus US3, US4, and US5 gene.
AB  - Here, we first present unique short (US)3, US4, and US5 gene sequences, with
      analysis, of duck enteritis virus (DEV) vaccine strain C-KCE. The assembled
      sequence comprises 5,742 nucleotides, which are amplified from the DEV genome by
      single oligonucleotide-nested polymerase chain reaction with primers designed
      according to our previous acquired sequence deposited in GenBank (accession no.
      EF619046). The predicted gene arrangement is colinear with the alphaherpesvirus
      herpes simplex virus within the US region. The N-glycosylated sites, signal
      peptide, transmembrane helices, RNA polymerase II transcriptional control
      elements, and polyadenylation signal, were predicted with network prediction
      programs. Phylogenetic analysis of the three putative proteins revealed that they
      had a close evolutionary relationship with the subfamily of Alphaherpesvirinae.

PMID- 19153826
TI  - The evolution of Epstein-Barr virus inferred from the conservation and mutation
      of the virus glycoprotein gp350/220 gene.
AB  - To study variations of Epstein-Barr virus (EBV), we analyzed the gp350/220 gene
      for several cell lines and Japanese wild isolates using direct sequencing. The N
      terminal region was highly conserved in all EBVs except for Jijoye/P3HR-1 and a
      few isolates. The variation of the region coincided with EBV types A and B (also
      referred to as types 1 and 2) and were, respectively, designated as the types a
      and b. The type A/a was detected in most Japanese cell lines and wild isolates,
      and was classified as China1 type with latent membrane protein (LMP) 1 gene. The
      type B/b was detected in only a few wild isolates with the Med and China2 types.
      The C-terminus had more diversity than the N-terminus and lacked the divergence
      between types A/a and B/b. The phylogenetic analyses of the gp350/220 and LMP1
      genes may suggest a mode of EBV evolution into types A/a and B/b and then to LMP1
      subtypes.

PMID- 19153827
TI  - Sensory over-responsivity in elementary school: prevalence and social-emotional
      correlates.
AB  - Sensory over-responsivity (SOR) towards tactile and auditory input can impact
      children's participation in academic and social activities; however the
      prevalence of SOR behaviors and their relation to social-emotional problems and
      competence has not been rigorously studied. This study investigated SOR in a
      representative sample of elementary school-aged children (n = 925, 50% boys, ages
      7-11 years) who were followed from infancy. Sixteen percent of parents reported
      that at least four tactile or auditory sensations bothered their children. Being
      bothered by certain sensations was common while others were relatively rare.
      Parents of children with versus without elevated SOR in school-age reported
      higher frequencies of early and co-occurring internalizing, externalizing, and
      dysregulation problems, and lower levels of concurrent adaptive social behaviors.
      Early identification of elevated SOR and assessment of concurrent social
      emotional status are important to minimize their impact on social adaptive
      behaviors at school age.

PMID- 19153828
TI  - Adjuvant goserelin and ovarian preservation in chemotherapy treated patients with
      early breast cancer: results from a randomized trial.
AB  - The purpose of this randomized study was to examine if goserelin concomitant to
      CMF-chemotherapy as adjuvant treatment for premenopausal breast cancer, protects
      the ovaries from premature failure. A total of 285 premenopausal breast cancer
      patients, in a randomized adjuvant trial (Zoladex in premenopausal patients
      (ZIPP)), were assigned to a study on ovarian function. Node positive patients
      were assigned to CMF-(cyclophosphamide, methotrexate and 5-fluorouracil)
      chemotherapy in addition to endocrine therapy. All patients were randomly
      assigned to receive 2 years of goserelin, goserelin plus tamoxifen, tamoxifen
      alone or no endocrine treatment. We studied, if menses were affected in the
      treatment groups, up to 36 months after randomization. One year after completed
      CMF- and endocrine therapy, 36% of the women in the goserelin group reported
      menses, compared to 7% in the goserelin plus tamoxifen group, 13% in the
      tamoxifen group and 10% of the controls. Among women treated with goserelin,
      there was a statistically significant increase in the proportion of menstruating
      women, 1 year after completed treatment compared to at 24 months of treatment (P
      = 0.006), in contrast to all other treatment groups, who were unchanged or more
      often amenorrheic. In our study, there is some evidence of protective effect of
      goserelin on ovarian function in CMF treated women. This effect was not observed
      in the combined tamoxifen and goserelin treatment.

PMID- 19153829
TI  - Lapatinib plus capecitabine versus capecitabine alone for HER2+ (ErbB2+)
      metastatic breast cancer: quality-of-life assessment.
AB  - The randomized phase III trial EGF100151 demonstrated that the combination of
      lapatinib plus capecitabine (L + C) significantly improved time to progression
      (TTP) compared with capecitabine alone (C) in heavily pretreated patients with
      HER2+ (ErbB2+) advanced or metastatic breast cancer. This analysis assessed the
      effects of study treatments on quality of life (QOL) among patients in EGF100151.
      Quality of life was assessed using the Functional Assessment of Cancer Therapy
      Breast (FACT-B) and EuroQoL (EQ-5D) questionnaires. Patients completed
      questionnaires during efficacy and safety assessment visits (i.e., at screening
      visit, every 6 weeks for the first 24 weeks, every 12 weeks thereafter, and at
      discontinuation of study treatment). Primary analyses compared the treatment
      groups based on change from baseline QOL. Exploratory analyses compared
      proportion of patients achieving minimum important differences (MID) in QOL
      scores and the relationship between QOL and tumor status. Quality of life for
      patients in both treatment groups was maintained during 24 weeks of follow-up.
      Adjusted mean changes from baseline in all QOL scores for the L + C arm were
      comparable to those for the C arm. The between-group differences ranged from 0.7
      to 2.2 (FACT-B total) and 0.3 to 1.8 (EQ-5D visual analog scale) and were
      consistently in favor of the L + C arm, although not statistically significant.
      Patients with an objective tumor response or stable disease showed clinically
      meaningful differences in QOL scores compared to patients with progressive
      disease. A greater proportion of patients receiving L + C versus C achieved the
      MID for all five QOL scores, although differences were not statistically
      significant. The addition of lapatinib to capecitabine significantly increases
      TTP without any evidence of a deleterious effect on patients' QOL, confirming its
      clinical benefit in this heavily pretreated patient population with advanced
      HER2+ breast cancer that has progressed on trastuzumab therapy.

PMID- 19153831
TI  - Breast cancer in a transitional society over 18 years: trends and present status
      in Shanghai, China.
AB  - As a metropolis with rapid social and economic development over the past three
      decades, Shanghai has a breast cancer incidence that surpasses all other cancer
      registries in China. In order to estimate the regular changing patterns of female
      breast cancer in urban Shanghai, population-based incidence data from 1975 to
      2004 were studied. In addition, a one-hospital-based in-patient database of 7,443
      female breast cancer patients treated surgically between January-1990 and July
      2007 were reviewed, retrospectively. We observed that breast cancer incidence
      increased dramatically over the past 30 years and documented a peak incidence
      represented by the middle-age group (45-59 years), which emerged in the last 20
      years. The incidence peak moved from the 40-44 year group in the previous two
      decades to the 50-54 year group in the most recent decade. Median age at
      diagnosis was earlier in Shanghai than in the western countries, although it
      increased from 47.5-year in 1990 to 50-year in 2007. Considerably higher exposure
      to reproductive risk factors and relatively fewer hormone-dependent cases were
      observed. The proportion of asymptomatic cases detected by screening gradually
      increased, as well as that of early-stage cases (from 78.6% in 1990 to 93.3% in
      2007) and carcinoma in situ (14.7% in 2007). Analysis of surgical treatment
      patterns suggested a trend of less-invasive options. Both age of peak incidence
      and median age at diagnosis increase with time, which suggests that increased
      incidence trending along with increasing age, will be observed in the future.
      Consequently, specific screening protocol should be refined to consider birth
      cohorts.

PMID- 19153830
TI  - Association between CYP2D6 genotype and tamoxifen-induced hot flashes in a
      prospective cohort.
AB  - Women with reduced CYP2D6 activity have low endoxifen concentrations and likely
      worse long term benefits from tamoxifen. We investigated the association between
      CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. We
      collected hot flash frequency and severity data over 12 months from 297 women
      initiating tamoxifen. We performed CYP2D6 genotyping using the AmpliChip CYP450
      test and correlated inherited genetic polymorphisms in CYP2D6 and tamoxifen
      induced hot flashes. Intermediate metabolizers had greater mean hot flash scores
      after 4 months of tamoxifen therapy (44.3) compared to poor metabolizers (20.6, P
      = 0.038) or extensive metabolizers (26.9, P = 0.011). At 4 months, we observed a
      trend toward fewer severe hot flashes in poor metabolizers compared to
      intermediate plus extensive metabolizers (P = 0.062). CYP2D6 activity may be a
      modest predictive factor for tamoxifen-induced hot flashes. The presence or
      absence of hot flashes should not be used to determine tamoxifen's efficacy.

PMID- 19153832
TI  - N-acetyl cysteine enhances imatinib-induced apoptosis of Bcr-Abl+ cells by
      endothelial nitric oxide synthase-mediated production of nitric oxide.
AB  - INTRODUCTION: Imatinib, a small-molecule inhibitor of the Bcr-Abl kinase, is a
      successful drug for treating chronic myeloid leukemia (CML). Bcr-Abl kinase
      stimulates the production of H(2)O(2), which in turn activates Abl kinase. We
      therefore evaluated whether N-acetyl cysteine (NAC), a ROS scavenger improves
      imatinib efficacy. MATERIALS AND METHODS: Effects of imatinib and NAC either
      alone or in combination were assessed on Bcr-Abl(+) cells to measure apoptosis.
      Role of nitric oxide (NO) in NAC-induced enhanced cytotoxicity was assessed using
      pharmacological inhibitors and siRNAs of nitric oxide synthase isoforms. We
      report that imatinib-induced apoptosis of imatinib-resistant and imatinib
      sensitive Bcr-Abl(+) CML cell lines and primary cells from CML patients is
      significantly enhanced by co-treatment with NAC compared to imatinib treatment
      alone. In contrast, another ROS scavenger glutathione reversed imatinib-mediated
      killing. NAC-mediated enhanced killing correlated with cleavage of caspases, PARP
      and up-regulation and down regulation of pro- and anti-apoptotic family of
      proteins, respectively. Co-treatment with NAC leads to enhanced production of
      nitric oxide (NO) by endothelial nitric oxide synthase (eNOS). Involvement of
      eNOS dependent NO in NAC-mediated enhancement of imatinib-induced cell death was
      confirmed by nitric oxide synthase (NOS) specific pharmacological inhibitors and
      siRNAs. Indeed, NO donor sodium nitroprusside (SNP) also enhanced imatinib
      mediated apoptosis of Bcr-Abl(+) cells. CONCLUSION: NAC enhances imatinib-induced
      apoptosis of Bcr-Abl(+) cells by endothelial nitric oxide synthase-mediated
      production of nitric oxide.

PMID- 19153833
TI  - Blue maize: morphology and starch synthase characterization of starch granule.
AB  - The use of pigmented maize varieties has increased due to their high anthocyanins
      content, but very few studies are reported about the starch properties of these
      grains. The aim of this work was to isolate the starch granules from pigmented
      blue maize and carry out the morphological, physicochemical, and biochemical
      characterization studies. The proximate composition of starch granules showed
      high protein contents, after purification, the blue maize starch presented lower
      protein amount than starch from white maize (control). Although the purity of
      starch granules was increased, the damaged starch (determined for the Maltase
      cross absence) was also increased. Scanning electron microscopy showed the
      presence of some pores and channels in the blue maize starch. The electrophoretic
      protein profiles showed differences in the bands that correspond to the enzymes
      involved in the starch biosynthesis; these differences could explain the
      variation in morphological characteristics of blue maize starches against starch
      from white maize.

PMID- 19153835
TI  - Water purification by sulfide-containing activated carbon.
AB  - We investigated a new kind of activated carbon named gaiasafe-Formstoff as an
      agent for powerful heavy metal reduction. This activated carbon contains highly
      dispersed sulfide compounds. Our investigations with lead containing wastewaters
      showed an outstanding metal sulfide precipitation power of the new agent. The
      lead reduction rates are independent of wastewater parameters like lead
      concentration and complexing agent concentration. Contacted as powder or as a
      fixed bed with wastewater gaiasafe-Formstoff showed the best cleaning capacity in
      comparison to all other agents tested. Investigations with gaiasafe-Formstoff
      about its ability to reduce the contents of further heavy metals in wastewater
      are under way. The gaiasafe-Formstoff reaction products with wastewater represent
      an energy-rich and raw material-rich resource when fed to metallurgical
      processes.

PMID- 19153836
TI  - Concentrations of phthalate esters and identification of other additives in PVC
      children's toys.
AB  - This study was intended to provide data on the composition of soft PVC toys,
      addressing the widest practicable range of chemical additives and including non
      phthalate additives. The study also included toys from as many countries as
      possible, since for many, no data were available. A total of 72 toys were
      purchased in 17 countries. The majority (64) were PVC or had PVC sections. In
      almost all the soft PVC toys analysed, phthalates comprised a sizeable proportion
      (most frequently 10-40%) of the total weight of the toy. The predominant
      phthalates detected were diisononyl phthalate (DINP) and di(2-ethylhexyl)
      phthalate (DEHP). Other phthalates identified in high concentrations in some toys
      include isomeric mixes of diisooctyl phthalate (DIOP) and diisodecyl phthalate
      (DIDP). The estrogenic chemical nonylphenol was isolated from 13 toys, while 2
      toys were found to contain the fungicide Fungitrol 11 (Folpet). 78% of PVC toys
      contained one or more extractable organic compounds in addition to those reported
      above.

PMID- 19153837
TI  - The natural production of organobromine compounds.
AB  - Organobromine chemicals are produced naturally by an array of biological and
      other chemical processes in our environment. Some of these compounds are
      identical to man-made organobromine compounds, such as methyl bromide, bromoform,
      and bromophenols, but many others are entirely new moleclar entities, often
      possessing extraordinary and important biological properties. Although only a few
      natural organobromine compounds had been discovered up to 1968, this number as of
      early 1999 is more than 1,600, and new examples are being discovered continually.
      Organobromine compounds are produced naturally by marine creatures (sponges,
      corals, sea slugs, tunicates, sea fans) and seaweed, plants, fungi, lichen,
      algae, bacteria, microbes, and some mammals. Many of these organobromine
      compounds are used in chemical defense, to facilitate food gathering, or as
      hormones.

PMID- 19153841
TI  - SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic
      substances for the North American Great Lakes. Part I: Structure of the scoring
      and ranking system.
AB  - Hundreds of chemical contaminants have been identified in the Great Lakes System
      of North America. Depending on the agency or organization, various subset lists
      of these contaminants have been identified as chemicals of potential concern.
      However, there is no agreement on the method that should be used to make
      management decisions. Except for consensus on approximately 40 chemicals that
      most North American agencies agree can cause deleterious effects if released into
      the environment, no agreement has been reached regarding the priority that
      contaminants should receive for further action. That leaves hundreds of chemicals
      that have been, are being, or potentially could be released into the environment
      that have not been evaluated yet. A profile for potential chemicals of concern is
      generally thought to include persistence in the environment, potential to
      bioaccumulate, and ability to cause toxic effects at environmentally relevant
      concentrations. Except for the International Joint Commission's definition of
      persistence (> 8 weeks residence time in air, water, soil or sediment), there is
      little concurrence about what defines these characteristics. For instance, the
      State of Michigan currently has no established definitions or profiles of
      persistent, bioaccumulative, toxic substances. Furthermore, there is no standard
      process to rank chemicals relative to these characteristics. The Chemical Scoring
      and Ranking Assessment Model (SCRAM) has been developed to provide a process to
      rank-order chemicals based on these characteristics. The SCRAM system was
      developed primarily for use in the Great Lakes region of North America and
      particularly in Michigan, but it is not site-specific. Use of this system may
      assist in pollution prevention activities and other future chemical control
      efforts, allowing attention to be focused first on those chemicals likely to
      present the greatest hazard.

PMID- 19153844
TI  - Analysis of masseter muscle oxygenation and mandibular movement during
      experimental gum chewing with different hardness.
AB  - OBJECTIVE: The purpose of this study was to analyze masseter muscle oxygenation
      changes and mandibular movements in the experimental chewing of gums with
      different hardness. MATERIAL AND METHODS: Subjects for this experiment comprised
      23 male volunteers with normal occlusion. Mean age (SD) was 28.3 (2.2) years.
      Three kinds of gum with mean fracture stresses of 3.52 x 10(4) N/m(2) (Gum 1),
      5.35 x 10(4) N/m(2) (Gum 2), and 14.0 x 10(4) N/m(2) (Gum 3) were used. The
      subjects were instructed to chew gum for 80 s (100 strokes) on the voluntary
      chewing side at a pace of 1.25 strokes/s. Oxygen saturation in the masseter
      muscle and mandibular movement during gum chewing were recorded simultaneously
      using near-infrared spectroscopy tissue oximetry and mandibular kinesiography.
      RESULTS: For Gum 1, no subjects showed any significant changes in oxygen
      saturation during gum chewing. For Gum 2, 10 subjects showed no significant
      changes, whereas the other 13 showed significant decreases in oxygen saturation.
      For Gum 3, significant decreases were seen in all subjects. Chewing motions were
      larger and velocity was higher in gum chewing with decreases in masseter muscle
      oxygen saturation compared to chewing showing no significant changes.
      CONCLUSIONS: The results suggest that the harder texture of gum enlarges chewing
      motion and increases chewing velocity, with an increase in the contribution of
      anaerobic metabolism to energy yield in masseter muscle. Differences in the
      responses to gum hardness may indicate individual differences in muscle fatigue
      tendencies when chewing harder foods.

PMID- 19153845
TI  - Canal wall reconstruction and mastoid obliteration in canal wall down
      tympanomastoidectomized patients.
AB  - CONCLUSION: Posterior canal reconstruction using autogenous bone pate and mastoid
      obliteration with allogenous cancellous bone chips (ACBCs) is a useful method to
      eliminate cavity problems after canal wall down tympanomastoidectomy (CWDT). It
      is also an appropriate method to obtain adequate middle ear space for hearing
      gain and to apply hearing aids for patients with poor eustachian tube function
      after surgery. OBJECTIVE: This study was performed to suggest a new technique for
      posterior canal reconstruction and mastoid obliteration and to evaluate the
      outcome of the surgery. PATIENTS AND METHODS: The entire posterior canal was
      reconstructed with autogenous bone pate, and the new isolated mastoid cavity was
      obliterated with ACBCs in patients who had undergone CWDT and suffered from
      cavity problems. Outcomes were measured by external auditory canal shape,
      condition of the neotympanum, hearing outcome, improvement of cavity problems,
      and surgical complications. RESULTS: In 90.9%, the reconstructed canal wall
      maintained a cylindrical shape. The drum healed without perforation/retraction in
      90.9%. The average air-bone gap value was 34.5 dB hearing level (HL) before the
      staged operation and 17.8 dB HL after the staged operation; 95.5% had no more
      cavity problems. Minor postauricular wound infection was the most common
      complication (13.6%).

PMID- 19153843
TI  - Cellular and molecular neurobiology of brain preconditioning.
AB  - The tolerant brain which is a consequence of adaptation to repeated nonlethal
      insults is accompanied by the upregulation of protective mechanisms and the
      downregulation of prodegenerative pathways. During the past 20 years, evidence
      has accumulated to suggest that protective mechanisms include increased
      production of chaperones, trophic factors, and other antiapoptotic proteins. In
      contrast, preconditioning can cause substantial dampening of the organism's
      metabolic state and decreased expression of proapoptotic proteins. Recent
      microarray analyses have also helped to document a role of several molecular
      pathways in the induction of the brain refractory state. The present review
      highlights some of these findings and suggests that a better understanding of
      these mechanisms will inform treatment of a number of neuropsychiatric disorders.

PMID- 19153846
TI  - Long-term follow-up of infants (4-11 months) fitted with cochlear implants.
AB  - CONCLUSION: In this study the outcomes from several indices (Category of Auditory
      Performance, CAP; Peabody Picture Vocabulary Test (Revised), PPVT-R; Test of
      Reception of Grammar, TROG; and Speech Intellegibility Rating, SIR) in three
      groups of children with different ages at implantation (from 4 to 36 months) with
      a follow-up time from 4 to 9 years demonstrate that very early cochlear
      implantation (<11 months) provides normalization of audio-phonologic parameters
      with no complications. OBJECTIVES: The aim of the present study was to
      investigate the efficacy of cochlear implants (CIs) in infants who were implanted
      at < 11 months of age versus children operated at later age (i.e. 12-36 months)
      and to document whether children who receive a CI below 11 months of age are able
      to achieve age-appropriate expected spoken language skills, at a follow-up time
      from 4 to 9 years. SUBJECTS AND METHODS: From November 1998 to November 2007, 185
      children received CIs and 34 received auditory brainstem implants in our
      department. The present study focuses on 13 children implanted at ages younger
      than 12 months (4-11 months; mean, 8.2; SD = 2.4) and fitted with CIs between
      November 1998 and March 2004. To avoid bias these children were selected from a
      larger longitudinal cohort of pediatric CI recipients fitted with CIs because
      they all were implanted with the same cochlear device (Nucleus CI 24 M) during
      the same period. Postoperatively auditory abilities were evaluated at the latest
      follow-up, from 4 to 9 years after surgery, with CAP, PPVT-R, TROG, and SIR. The
      results obtained in this group of 13 children were compared with those obtained
      in two groups of children implanted at later ages (12-23 and 24-36 months,
      respectively). RESULTS: No complication has been observed so far. The highest
      score of CAP function was achieved in all the three groups but at different
      intervals from CI activation as function of age at CI implantation. The rate of
      receptive language growth (PPVT-R) provides distinctive evidence that only the
      scores of the first group overlap the line of normal-hearing children, whereas
      the second and third group never reached the values of normal peers even after 9
      years of CI use. TROG outcomes clearly indicate that only children from the first
      group (77%) are in the 76-100 percentile at 5 years follow-up. At 9 years follow
      up, 100% of children in the first group, 38% in the second group, and 20% in the
      third group are in the 76-100 percentile. The SIR outcomes at the 5 years follow
      up indicate that none of children was identified within the first two categories,
      only children from the third group (18%) were identified in category 3, all
      infants of the first group, 80% of group 2, and 63% of the third group were
      identified in category 5. At the 9 years follow-up, the number of children from
      the third group identified in category 3 was reduced to 10%, the second and third
      groups displayed a slightly higher percentage of children in category 5, but the
      difference from the values observed at the 5-year follow-up is not significant.

PMID- 19153847
TI  - The influence of cholesterol on the motility of cochlear outer hair cells and the
      motor protein prestin.
AB  - CONCLUSIONS: We provide evidence that cholesterol reduces electromotility in a
      dose-dependent matter. The data show that cholesterol modulates electromotility
      mainly by influencing the motor protein prestin, less by affecting the passive
      membrane properties. OBJECTIVES: Elevated serum cholesterol is linked to inner
      ear disorders and may influence hearing by altering membrane properties of outer
      hair cells (OHCs) and by affecting the motor protein prestin. In this study we
      wanted to determine whether cholesterol modulates the electromotility of OHCs and
      if this modulation results from effects on the membrane properties or on the
      motor protein prestin. MATERIALS AND METHODS: The motile responses of 12 isolated
      OHCs were investigated at increasing concentrations of 0, 0.1, and 1 mM
      extracellular cholesterol using the patch clamp technique and continuous video
      image analysis. To study effects on prestin, experiments were performed in 12
      cells with half activated protein function and concentrations of 0 and 1 mM
      cholesterol. RESULTS: Cholesterol at a concentration of 0.1 mM had no effect on
      motility. A concentration of 1 mM reduced maximal evoked shortening significantly
      by 29% in the depolarizing and by 9% in the hyperpolarizing direction.
      Investigating half activated motor proteins, 1 mM cholesterol reduced movements
      significantly by 18%, elongations decreased nonsignificantly by 5%.

PMID- 19153848
TI  - Use of anatomic or invasive markers in association with skin surface registration
      in image-guided surgery of the temporal bone.
AB  - CONCLUSION: The use of an invasive marker in the ipsilateral temporal bone with
      mid-facial skin contouring for registration improved the position accuracy (PA)
      to levels required for otological and neuro-otological procedures. OBJECTIVE: The
      aim of this study was to compare the PA after skin contouring with the
      combination of anatomic landmarks or a local invasive marker and skin surface
      registration for intratemporal computer-assisted navigation. PATIENTS AND
      METHODS: Thirty-three patients undergoing a lateral skull base procedure with the
      Digipointeur system (Collin, Bagneux, France) based on CT scan were included in
      this study. Registration was obtained by a mid-facial skin contouring. In the
      first protocol (n=8), PA was evaluated and the position corrected for three
      intratemporal landmarks before evaluation of the target (round window). In a
      second protocol (n=25), a titanium screw was placed in the ipsilateral mastoid
      region before imaging. PA was measured before and after screw registration for
      five intratemporal landmarks. RESULTS: In the first protocol, PA did not improve
      after the registration of the landmarks, and PA of the target was evaluated as
      4.9+/-0.64 mm. In the second protocol, PA was reduced after screw registration
      for all landmarks with a mean PA ranging from 0 to 2.3 mm.

PMID- 19153849
TI  - Time to diagnosis in the National Registry of Veterans with Amyotrophic Lateral
      Sclerosis.
AB  - Our objective was to determine the interval from symptom onset to diagnosis, and
      to evaluate associated factors in a cohort of U.S. Veterans with motor neuron
      diseases. We retrospectively evaluated 1359 patients enrolled in the National
      Registry of Veterans with Amyotrophic Lateral Sclerosis (ALS). The main outcome
      measures were time from symptom onset to first diagnosis and to second opinion.
      Predictor variables included age at symptom onset, year of symptom onset, race,
      onset site, final diagnosis, number of diagnostic tests performed and clinical
      sites visited. Median time to first diagnosis was 11 months; median time to
      second opinion was two months. In a multivariable model, more recent calendar
      year of symptom onset, younger age, bulbar onset and a diagnosis of ALS versus
      non-ALS motor neuron disease were all significantly associated with a shorter
      time to first diagnosis. Later year of symptom onset and white race were
      significantly associated with a shorter time to second opinion. While the
      interval from symptom onset to diagnosis, and many of the associated factors are
      similar between our large cohort of U.S. Veterans with ALS and other smaller
      published cohorts, we found that the diagnostic interval among U.S. Veterans has
      significantly decreased over time.

PMID- 19153851
TI  - Lamp oil poisoning: did the European guideline reduce the number and severity of
      intoxications?
AB  - INTRODUCTION: In 1997, a European guideline concerning the viscosity and surface
      tension of lamp oil was adopted to reduce instances and severity of lamp oil
      intoxications. In 2005, the Dutch National Poisons Information Centre
      investigated lamp oil intoxications to determine whether they differed in
      severity from the intoxications reported before the guideline was adopted.
      METHODS: We compared the data prospectively collected on lamp oil intoxications
      reported to our center in 2005 and in 1996. RESULTS: In 2005 and 1996,
      respectively 152 and 165 cases were included. The frequency of the symptoms and
      diagnosed pneumonitis did not differ significantly between those years. In 2005,
      ingestion of a transparent lamp oil seemed to be associated with a greater risk
      of serious respiratory symptoms than ingestion of colored oil. CONCLUSION:
      Despite the directive, frequency and severity of symptoms of lamp oil ingestions
      remain disturbing. Consequently, further actions concerning packaging and
      labeling of lamp oil, design of oil lamps, education of parents, and additions to
      the current guideline should be considered.

PMID- 19153852
TI  - Subcutaneous Crotaline Fab antivenom for the treatment of rattlesnake
      envenomation in a porcine model.
AB  - INTRODUCTION: This study was designed to investigate whether the local,
      subcutaneous injection of Crotaline Fab antivenom (CroFab) at the rattlesnake
      envenomation site would result in less extremity edema when compared to
      intravenous (i.v.) antivenom infusion alone. METHODS: This is a randomized, three
      arm laboratory experiment using a porcine model. Each animal was anesthetized,
      intubated, and maintained on mechanical ventilation. About 6 mg/kg of Crotalus
      atrox venom was injected subcutaneously at the hock of the right hind leg.
      Animals were then randomized to immediately receive subcutaneous and i.v.
      antivenom (SC/IV), i.v. antivenom only, or saline control. SC/IV animals received
      two vials of CroFab subcutaneously at the envenomation site and two vials
      intravenously. IV animals received four vials of CroFab intravenously. Limb edema
      was tracked by serial circumference and volumetric measurements over an 8-h
      period. Limb circumference was measured at four pre-determined locations hourly.
      Limb volume was measured by a water displacement method at baseline, 4, and 8 h.
      RESULTS: Twenty-six animals were randomized to the three treatment groups. The
      SC/IV and IV arms included nine animals each. Two animals in the SC/IV group died
      suddenly during the study, leaving seven animals for data analysis. There were
      eight controls. Increasing limb edema was observed in all groups. No differences
      were detected in limb circumferences or limb volumes between control and either
      treatment arms. CONCLUSION: In this porcine model of crotaline envenomation, no
      differences in limb edema were found between animals treated with SC/IV or IV
      CroFab when compared to saline controls.

PMID- 19153853
TI  - Preparation of crotaline F-ab antivenom (CroFab) with automated mixing methods:
      in vitro observations.
AB  - BACKGROUND: Crotaline Polyvalent Ovine Fab antivenom (CroFab, Savage Laboratories
      and Protherics Inc., Brentwood, TN, USA) preparation requires that the
      lyophilized powder be manually reconstituted before use. We compared automated
      methods for driving the product into solution with the standard manual method of
      reconstitution, and the effect of repeated rinsing of the product vial, on the
      per-vial availability of antivenom. METHODS: Normal saline (NS, 10 mL) was added
      to 12 vials of expired CroFab. Vials were assigned in pairs to each of six mixing
      methods, including one pair mixed manually as recommended by the product package
      insert. Each vial's contents were diluted to a final volume of 75 mL of normal
      saline. Protein concentration was measured with a colorimetric assay. The fluid
      left in each vial was removed and the vial was washed with 10 mL NS. RESULTS:
      Total protein yield from each step was calculated. There was no significant
      change in protein yield among three of five automated mixing methods when
      compared to manual reconstitution. Repeat rinsing of the product vial with an
      additional 10 mLs of fluid added to the protein yield regardless of the mixing
      method used. DISCUSSION: We found slightly higher protein yields with all
      automated methods compared to manual mixing, but only two of five comparisons
      with the standard mixing method demonstrated statistical significance. However,
      for all methods tested, the addition of a second rinsing and recovery step
      increased the amount of protein recovered considerably, presumably by allowing
      solution of protein trapped in the foamy residues. CONCLUSION: Automated mixing
      methods and repeat rinsing of the product vial may allow higher protein yields in
      the preparation of CroFab antivenom.

PMID- 19153854
TI  - Transportation of peripheral blood progenitor cell products: effects of time,
      temperature and cell concentration.
AB  - BACKGROUND AIMS: Peripheral blood progenitor cell (PBPC) products are often
      transported at high cell concentrations (>200x10(9)/L) over long distances,
      requiring >36 h transport time. METHODS: Fresh PBPC samples from 12 healthy
      donors were studied with various viability assays regarding the effects of
      temperature, cell concentration and duration of storage. RESULTS: Trypan blue
      exclusion was far less sensitive to cell damage than two-color fluorescence for
      CD34 and 7-AAD, and colony-forming unit-granulocyte-macrophage (CFU-GM) assays;
      the latter assay proved the most sensitive. All products stored at 4 degrees C
      maintained their viability for up to 4 days. Thus, at 96 h, recovery of viable
      CD34(+) cells was still 82%, and of CFU-GM 57%, even at concentrations of
      200x10(9)/L. Higher storage temperatures rapidly decreased the viability, with
      extensive variation between donors. At room temperature 80% of viable CD34(+)
      cells and >90% of CFU-GM were lost after 48 h of storage at 200x10(9)/L. Lower
      cell concentrations allowed storage at higher temperatures: at 17 degrees C a
      concentration of 50x10(9)/L resulted in only 5% loss of viable CD34(+) cells
      after 48 h, while the loss was >30% at 200x10(9)/L. CONCLUSIONS: PBPC products
      should be transported at 4 degrees C. Dilution of the product may partly
      compensate for slightly higher temperatures. Trypan blue exclusion should be
      abandoned as a method for assessing viability after prolonged transportation.
      Proliferative assays should be used to validate transportation conditions.

PMID- 19153855
TI  - Activated autologous T cells exert an anti-B-cell chronic lymphatic leukemia
      effect in vitro and in vivo.
AB  - BACKGROUND AIMS: The impact of chronic lymphatic leukemia (CLL) tumor burden on
      the autologous immune system has already been demonstrated. This study attempted
      to elucidate the molecular mechanisms underlying T-cell immunologic deficiencies
      in CLL. METHODS: Freshly isolated CD3(+) T cells from patients with a diagnosis
      of CLL and healthy donors were analyzed by gene expression profiling. Activated T
      cells from 20 patients with CLL were tested in vitro for cytotoxicity against
      mutated and unmutated autologous B cells and DAUDI, K562 and P815 cell lines. To
      investigate T-cell mediated cytotoxicity in vivo, we co-transplanted OKT3
      activated T lymphocytes and autologous B-cell CLL (B-CLL) cells into NOD/SCID
      mice. RESULTS: Gene expression profiles of peripheral blood T cells from B-CLL
      patients showed 25 down-regulated, and 31 up-regulated, genes that were mainly
      involved in cell differentiation, proliferation, survival, apoptosis,
      cytoskeleton formation, vesicle trafficking and T-cell activation. After culture,
      the T-cell count remained unchanged, CD8 cells expanded more than CD4 and a
      cytotoxicity index >30% was present in 5/20 patients. Cytotoxicity against B
      autologous leukemic cells did not correlate with B-cell mutational status. Only
      activated T cells exerting cytotoxicity against autologous leukemic B cells
      prevented CLL in a human-mouse chimera. CONCLUSIONS: This study indicates that
      patients with CLL are affected by a partial immunologic defect that might be
      somewhat susceptible to repair. This study identifies the molecular pathways
      underlying T-cell deficiencies in CLL and shows that cytotoxic T-cell functions
      against autologous B-CLL can be rebuilt at least in part in vitro and in vivo.

PMID- 19153858
TI  - A comparison of match demands between elite and semi-elite rugby league
      competition.
AB  - The purpose of this study was to examine differences in physical performance and
      game-specific skills between elite and semi-elite rugby league players during
      match-play. Time-motion analysis was used to determine physical and game-specific
      skill match demands in 17 elite and 22 semi-elite rugby league players. Physical
      performance (time, intensity of exercise, frequency, repeated-sprint ability, and
      speed measures) and game-specific skill measures (ball carries, supports, ball
      touches, play-the-balls, and tackles) were recorded per minute of playing time.
      The main findings were that total intensity (elite: 108.9 +/- 10.6 m . min(-1);
      semi-elite: 102.3 +/- 9.7 m . min(-1)), high-intensity exercise (elite: 36.7 +/-
      9.8 m . min(-1); semi-elite: 29.6 +/- 7.8 m . min(-1)), mean playing speed
      (elite: 6.6 +/- 0.6 km . h(-1); semi-elite: 6.2 +/- 0.6 km . h(-1)), and support
      play (elite: 0.29 +/- 0.16 . min(-1); semi-elite: 0.15 +/- 0.09 . min(-1)) were
      all higher during first-half match-play in the elite than semi-elite players (P <
      0.01). The elite players experienced decrements in most physical performance
      measures during the second-half of match-play (P < 0.01), which was not evident
      in the semi-elite players (P > 0.01). There were no differences in most physical
      performance and game-specific skill measures for the match between the two
      playing standards. These results show that while the two standards of competition
      have similar game-specific skills and physical demands during a match, there is
      variation within a match according to standard. Specifically, the higher physical
      demands placed on elite players during the first half could result in the earlier
      onset of physical fatigue towards the end of a match.

PMID- 19153859
TI  - Anthropometric and performance measures for the development of a talent detection
      and identification model in youth handball.
AB  - The first part of this study examined in which basic morphological and fitness
      measures Under-14 (n=34) and Under-16 (n=47) male youth handball players differ
      from reference samples of the same age (n=430 and n=570, respectively). To help
      develop a talent identification model, the second part of the study investigated
      which specific morphological and performance measures describe differences
      between elite (n=18) and non-elite (n=29) Under-16 youth handball players. The
      results showed that Under-16 handball players were significantly taller than the
      reference group; this was not the case in the Under-14 age group. Physical
      fitness in handball players was significantly better than in the reference
      groups. Multivariate analysis of covariance (maturation and chronological age as
      covariates) showed that the Under-16 elite players were heavier and had greater
      muscle circumferences than their non-elite peers. Elite players scored
      significantly better on strength, speed and agility, and cardiorespiratory
      endurance but not on balance, upper limb speed, flexibility or upper body
      muscular endurance. Maturation was a significant covariate in anthropometric
      measures but not in physical performance. Discriminant analysis between elite and
      non-elite players revealed that height, running speed, and agility are important
      parameters for talent identification. Specific anthropometric measures, in
      addition to some performance measures, are useful for talent identification in
      youth handball.

PMID- 19153860
TI  - Relationships between stroke parameters and critical swimming speed in a sprint
      interval training set.
AB  - The aim of this study was to determine whether a relationship exists between
      stroke parameters and critical swimming speed (which is defined as the speed that
      can theoretically be maintained without exhaustion). Stroke parameters (stroke
      rate and length) and velocity were recorded for each 25-m length during a
      controlled sprint interval training set in which participants swam one of the
      four competitive strokes at a range of intensities below, at, and above critical
      speed. Eleven participants (8 females, 3 males; age 17.9 +/- 0.9 years) completed
      a progressive (descending) set of 8 x 100 m repetitions in a 25-m pool according
      to target times that ranged in intensity from 65% to 100% of the swimmer's best
      time (the intensity for each repetition increased by 5% throughout the set). The
      data showed that participants reached critical speed on the fourth repetition and
      that substantial and unpredictable changes in stroke parameters occurred once
      critical speed had been reached. Specifically, post-critical speed stroke rate
      and stroke length were significantly (P < 0.01) greater and less, respectively,
      than the pre-critical speed values, and these changes occurred in an abrupt and
      non-linear manner. Overall, the findings suggest that critical speed represents a
      transition point between two different sets of stroke parameter relationships-
      one for low-intensity aerobic swimming and one for high-intensity anaerobic
      swimming.

PMID- 19153861
TI  - Peaking for optimal performance: Research limitations and future directions.
AB  - A key element of the physical preparation of athletes is the taper period in the
      weeks immediately preceding competition. Existing research has defined the taper,
      identified various forms used in contemporary sport, and examined the
      prescription of training volume, load, intensity, duration, and type (progressive
      or step). Current limitations include: the lack of studies on team, combative,
      racquet, and precision (target) sports; the relatively small number of randomized
      controlled trials; the narrow focus on a single competition (single peak)
      compared with multiple peaking for weekly, multi-day or multiple events; and
      limited understanding of the physiological, neuromuscular, and biomechanical
      basis of the taper. Future research should address these limitations, together
      with the influence of prior training on optimal tapering strategies, and the
      interactions between the taper and long-haul travel, heat, and altitude.
      Practitioners seek information on how to prescribe tapers from season to season
      during an athlete's career, or a team's progression through a domestic league
      season, or multi-year Olympic or World Cup cycle. Practical guidelines for
      planning effective tapers for the Vancouver 2010 and London 2012 Olympics will
      evolve from both experimental investigations and modelling of successful tapers
      currently employed in a wide range of sports.

PMID- 19153862
TI  - Difference-based meta-analytic procedures for between-participant and/or within
      participant designs: a tutorial review for sports and exercise scientists.
AB  - The aim of this paper is to provide a contemporary summary of statistical and non
      statistical meta-analytic procedures that have relevance to the type of
      experimental designs often used by sport scientists when examining
      differences/change in dependent measure(s) as a result of one or more independent
      manipulation(s). Using worked examples from studies on observational learning in
      the motor behaviour literature, we adopt a random effects model and give a
      detailed explanation of the statistical procedures for the three types of raw
      score difference-based analyses applicable to between-participant, within
      participant, and mixed-participant designs. Major merits and concerns associated
      with these quantitative procedures are identified and agreed methods are reported
      for minimizing biased outcomes, such as those for dealing with multiple dependent
      measures from single studies, design variation across studies, different metrics
      (i.e., raw scores and difference scores), and variations in sample size. To
      complement the worked examples, we summarize the general considerations required
      when conducting and reporting a meta-analysis, including how to deal with
      publication bias, what information to present regarding the primary studies, and
      approaches for dealing with outliers. By bringing together these statistical and
      non-statistical meta-analytic procedures, we provide the tools required to
      clarify understanding of key concepts and principles.

PMID- 19153864
TI  - Movement coordination patterns in triple jump training drills.
AB  - The aim of this study was to determine the effectiveness of training drills in
      replicating the lower extremity coordination patterns used during the triple
      jump. Three-dimensional kinematic data and synchronized ground reaction force
      data were collected during the hop-step transition of a triple jump and four
      related training drills. Relative motion plots and a modified version of the
      vector coding technique were used to quantify the coordination patterns of the
      lower extremities. Differences were observed in the coordination patterns between
      the triple jump and static drills, but not between the triple jump and dynamic
      drills, and these differences were mainly in the swing (free) leg. The results of
      this study suggest that if the primary purpose of the training drills is to
      replicate the movement patterns used in the triple jump, then dynamic drills are
      more effective than static drills. In addition, coaches should focus on the use
      of the free leg during these training drills so that the coordination patterns
      more closely replicate the triple jump. Finally, to provide a more holistic
      evaluation of training drills, future studies should investigate the similarity
      of the physical and musculoskeletal demands of jumps and drills.

PMID- 19153865
TI  - Social physique anxiety and physical activity in early adolescent girls: the
      influence of maturation and physical activity motives.
AB  - In this study, we examined the influence of maturation on social physique
      anxiety, the relationship between social physique anxiety and current and future
      physical activity levels, and the influence of motives for physical activity on
      this relationship in early adolescent girls (n=162; mean age = 11.8 +/- 0.3
      years). Participants completed the Pubertal Development Scale, the modified
      Social Physique Anxiety Scale, and the Motives for Physical Activity Scale at
      baseline and the Physical Activity Questionnaire for Older Children at baseline
      and 6 months later. The girls became less active across the 6 months and girls in
      the early stages of maturation had significantly lower social physique anxiety
      than the girls in the middle and late stages of maturation. Social physique
      anxiety was not related to current or future physical activity in the sample as a
      whole. Cluster analysis identified four groups with different motive profiles and
      the High Appearance and Fitness group demonstrated a moderate negative
      relationship between social physique anxiety and physical activity at phase 1,
      whereas the other groups did not. These findings indicate that social physique
      anxiety may increase with maturation and the relationship between social physique
      anxiety and physical activity is dependent on reasons for being active. For girls
      who are motivated to be active primarily by body-related reasons, social physique
      anxiety is likely to lead to lower levels of physical activity.

PMID- 19153866
TI  - High-intensity running in English FA Premier League soccer matches.
AB  - The aims of this study were to (1) determine the activity profiles of a large
      sample of English FA Premier League soccer players and (2) examine high-intensity
      running during elite-standard soccer matches for players in various playing
      positions. Twenty-eight English FA Premier League games were analysed during the
      2005-2006 competitive season (n=370), using a multi-camera computerised tracking
      system. During a typical match, wide midfielders (3138 m, s=565) covered a
      greater distance in high-intensity running than central midfielders (2825 m, s=
      73, P=0.04), full-backs (2605 m, s=387, P < 0.01), attackers (2341 m, s=575, P <
      0.01), and central defenders (1834 m, s=256, P < 0.01). In the last 15 min of a
      game, high-intensity running distance was approximately 20% less than in the
      first 15-min period for wide midfielders (467 m, s=104 vs. 589 m, s=134, P <
      0.01), central midfielders (429 m, s=106 vs. 534 m, s=99, P < 0.01), full-backs
      (389 m, s=95 vs. 481 m, s=114, P < 0.01), attackers (348 m, s=105 vs. 438 m,
      s=129, P < 0.01), and central defenders (276 m, s=93 vs. 344 m, s=80, P < 0.01).
      There was a similar distance deficit for high-intensity running with (148 m, s=78
      vs. 193 m, s=96, P < 0.01) and without ball possession (229 m, s=85 vs. 278 m,
      s=97, P < 0.01) between the last 15-min and first 15-min period of the game. Mean
      recovery time between very high-intensity running bouts was 72 s (s=28), with a
      28% longer recovery time during the last 15 min than the first 15 min of the game
      (83 s, s=26 vs. 65 s, s=20, P < 0.01). The decline in high-intensity running
      immediately after the most intense 5-min period was more evident in attackers
      (216 m, s=50 vs. 113 m, s=47, P < 0.01) and central defenders (182 m, s=26 vs. 96
      m, s=39, P < 0.01). The results suggest that high-intensity running with and
      without ball possession is reduced during various phases of elite-standard soccer
      matches and the activity profiles and fatigue patterns vary among playing
      positions. The current findings provide valuable information about the high
      intensity running patterns of a large sample of elite-standard soccer players,
      which could be useful in the development and prescription of specific training
      regimes.

PMID- 19153867
TI  - The effects of vibration on explosive and reactive strength when applying
      individualized vibration frequencies.
AB  - The aim of this study was to assess the effects of 8 weeks of whole-body
      vibrations on explosive and reactive leg strength. Thirty-three physically active
      students took part in the study and were randomly assigned to an individualized
      vibration group, a fixed-vibration group or a control group. The frequency of
      vibration was set to 30 Hz for the fixed-vibration group, whereas the frequency
      for the individualized-vibration group was determined by monitoring the
      participants' EMGrms activity. The participants in the two vibration groups were
      exposed three times a week for 8 weeks to a series of 10 x 1-min whole-body
      vibrations with a 1-min pause between series of vibrations and a 4-min pause
      after the first five series of vibrations. Jump height in the squat jump
      increased significantly in all three groups (by 11% for the individualized
      vibration group, p=0.001; by 3% for the fixed-vibration group, p=0.011; and by 2%
      for the control group, p=0.006), but countermovement jump height was not
      affected. In continuous rebound jumps by the individualized-vibration group,
      jumping height increased by 22% (p=0.006) and power increased by 18% (p=0.002).
      The results of this study suggest that the use of an individualized vibration
      frequency produces a greater response from the neuromuscular system and is more
      beneficial than vibrations at a fixed pre-selected frequency.

PMID- 19153868
TI  - Analogy versus explicit learning of a modified basketball shooting task:
      performance and kinematic outcomes.
AB  - The effects of differential instructional sets on motor skill acquisition were
      investigated using performance outcome and kinematic measures. Participants were
      provided with a single analogical instruction (analogy learning), a set of eight
      explicit (technical) instructions (explicit learning), or were not instructed
      (control). During a learning phase, participants (n=9 for each condition)
      performed a modified basketball shooting task over 3 days (160 trials per day).
      On the fourth day, participants performed a test phase consisting of two 40-trial
      retention tests, separated by a 40-trial secondary task transfer test, and
      completed a verbal protocol describing in detail the techniques that they had
      used to perform the task. No performance differences were found during the two
      retention tests, indicating similar amounts of learning for all groups. During
      the transfer test, performance deteriorated for both the explicit and control
      conditions, but not for the analogy condition. Participants in the analogy
      condition reported significantly fewer technical rules. Although no group
      differences were reported for kinematic variables, identification of movement
      components supported the claim that explicit learners exert conscious control
      over their movements, whereas analogy learners use a more implicit (unconscious
      or automatic) mode of movement control.

PMID- 19153869
TI  - Conceptual hypometria? An evaluation of conceptual mapping of space in
      Parkinson's disease.
AB  - When interacting with objects in their environment, patients with Parkinson's
      disease (PD) often make hypometric movements (e.g., micrographia). The purpose of
      this study was to learn if patients with PD, in the absence of overt actions or
      environmental stimuli, have egocentric (body-centered) conceptual
      (representational) hypometria. Actions can take place in either proximal or
      distal peri-personal space. Normally, the right hemisphere has a distal and the
      right a proximal attentional bias. We also want to learn if a patient with onset
      of disease in the right hemisphere would have a greater conceptual action
      hypometria than individuals with left hemispheric onset. Seventeen subjects with
      PD and 15 age-matched controls were given a questionnaire evaluating subjective
      perception of personal action space. The questionnaire asked individuals to rate,
      using a 0-5 scale, the distances between their body and hand when performing the
      various actions that take place in peri-personal space. When compared to control
      participants, participants with PD, and especially those with predominant left
      sided symptoms (right greater than left hemispheric dysfunction) had hypometric
      mental perceptions for actions that normally occur in far peri-personal space.
      Individuals with PD appear to demonstrate a conceptual hypometria, suggesting
      that there is a perturbation of their interactive representational maps and these
      maps appear to be more disordered by right than left hemisphere dysfunction.
      However, it is also possible that when making action distance computations,
      participants used covert actions and it was the hypometric covert actions that
      induced the computational hypometria.

PMID- 19153870
TI  - Sensory function in severe semilobar holoprosencephaly.
AB  - We report a 4-year-old child with severe semi-lobar holoprosencephaly (HPE) not
      expected to survive after birth. Magnetic resonance imaging (MRI) revealed
      agenesis of the corpus callosum, absence of the third ventricle, fused thalami
      and basal ganglia. To investigate sensory function, visual, auditory and
      somatosensory evoked potential and imaging studies were carried out. The visual
      response evoked by human face stimuli evoked larger responses over the left side
      of the holosphere as compared to responses evoked by checkerboard pattern, while
      auditory evoked potentials were evident over the frontal regions to both pure
      tones and speech stimuli. No consistent scalp somatosensory evoked potentials
      were evident. This case demonstrates that electrophysiological measures are able
      to identify and quantify sensory processing not expected to be present based on
      the anatomical presentation of the cortex in a child with severe HPE.

PMID- 19153871
TI  - Auditory pathways fail to re-establish normal cortical activation patterns in
      response to binaural stimulation following a unilateral lesion of the inferior
      colliculus.
AB  - The aim of this study was to investigate cortical activation in response to
      binaural stimulus presentations in an individual (FX) with a circumscribed
      traumatic hemorrhagic lesion of the right inferior colliculus. FX and control
      subjects were exposed to complex sounds while undergoing a functional magnetic
      resonance imaging assessment. Whereas normally-hearing individuals show well
      balanced bilateral activation patterns in response to binaural auditory
      stimulation, the same stimuli produced stronger activation in the left hemisphere
      in FX. Combined with previous data, these findings reinforce the notion that the
      inferior colliculus is an essential auditory relay and that its loss cannot be
      significantly compensated.

PMID- 19153872
TI  - 18q deletion syndrome: a neuropsychological case study.
AB  - The 18q deletion syndrome (18q-) is a chromosomal disorder involving deletion of
      the distal segment of chromosome 18. Typifying features include poor cerebral
      myelination, reduced intellectual functioning and developmental delay. The
      present study reports the case of an 8-year-old girl diagnosed with 18q-, whose
      genetic analysis revealed a break at q21.3. Comprehensive neuropsychological
      testing indicated impaired functioning across most cognitive domains. However,
      verbal abilities were intact. Given the preservation of verbal skills on a
      background of relatively global impairment, CB's genetic and cognitive profile
      has implications for delineation of neuropsychological features associated with
      specific breakpoints in 18q-.

PMID- 19153873
TI  - Underutilization of microsatellite instability analysis in colorectal cancer
      patients at high risk for Lynch syndrome.
AB  - OBJECTIVE: The revised Bethesda Guidelines were published to improve the
      efficiency of recognizing Lynch syndrome (LS) by identifying LS-related
      malignancies that should be analyzed for microsatellite instability (MSI). The
      aim of this study was to evaluate whether MSI analysis was performed in
      colorectal cancer patients at risk for LS according to the revised Bethesda
      Guidelines. MATERIAL AND METHODS: Patients diagnosed with colorectal cancer in 11
      Dutch hospitals in 2005 and 2006 were selected from a regional database. The
      patients were included in the study if they met any of the following criteria; 1)
      diagnosed with colorectal cancer <50 years, 2) a second LS-associated tumor prior
      to the diagnosis of colorectal cancer in 2005/2006, and 3) colorectal cancer <60
      years with a tumor displaying mucinous or signet-ring differentiation or
      medullary growth pattern. RESULTS: Of 1905 colorectal cancer patients, 169 met at
      least one of the inclusion criteria. MSI analysis had been performed in 23 (14%)
      of the 169 tumors. MSI status had been determined in 18 of 80 included patients
      aged <50 years, in 4 of 70 patients with a second LS-related tumor, and in 3 of
      41 patients aged <60 years with high-risk pathology features. CONCLUSIONS: There
      is marked underutilization of MSI analysis in patients at risk for LS. As a
      result LS might be underdiagnosed both in patients with colorectal cancer and in
      their relatives.

PMID- 19153874
TI  - Progress of tissue injury in appendicitis involves the serine proteases uPA and
      PAI-1.
AB  - OBJECTIVE: Serine proteases and the matrix metalloproteinases (MMPs) are key
      factors in the proteolytic cascade and participate in extracellular matrix (ECM)
      degradation. Fibrinolytic activators and inhibitors may have an effect on
      inflammatory cells, thereby modulating the inflammatory response. It is
      reasonable to assume that they may be implicated in the tissue injury in acute
      appendicitis that subsequently leads to appendix perforation. The purpose of this
      study was to investigate the expression and distribution of urokinase-type
      plasminogen activator (uPA) and plasminogen-activator inhibitor type 1 (PAI-1) in
      appendicitis. MATERIAL AND METHODS: Expression of uPA and expression of PAI-1
      were measured in tissue specimens from patients with appendicitis (n=30) and in
      control specimens (n=9), using the quantitative ELISA technique. Distribution of
      enzymes was studied with immunohistochemistry. The uPA and PAI-1 levels in the
      subgroups of appendicitis and controls were compared. RESULTS: The overall
      expressions of uPA and PAI-1 were greater in appendicitis than in control
      specimens (p <0.001 and p<0.0001, respectively). Expressions of uPA and PAI-1 in
      phlegmonous (n=15), gangrenous (n=6) and perforated appendicitis (n=9) were all
      higher than those in controls (n=9), (p<0.01). Moreover, the PAI-1 level was
      elevated in perforated appendicitis compared with phlegmonous appendicitis
      (p<0.01). uPA staining was observed in connection with vascular endothelial cells
      and the serosa stained intensely in specimens from perforated appendicitis.
      CONCLUSIONS: The expression of uPA and especially the over-expression of PAI-1
      seem to correlate to the progression of local inflammatory response in acute
      appendicitis.

PMID- 19153875
TI  - In vivo comparison of biomechanical, histological, and radiological properties of
      three techniques for tendon lengthening: an experimental study in rabbits.
AB  - Biomechanical, histological, and radiological properties of three different
      techniques of tendon lengthening - Z-plasty, modified Vulpius, and modified Baker
      - were investigated and compared. Sixty white female Angora rabbits (mean weight
      4.1 kg, range 3.9 kg- 4.2 kg) were randomly divided into three groups: Z-plasty,
      V-Y plasty (modified Vulpius technique), and U-T plasty (modified Baker
      technique). Histopathological, radiological, and biomechanical properties were
      evaluated at the third and sixth postoperative week. Qualitative analysis of
      ultrasound examination showed that Z-plasty had the most irregular echo pattern
      at the third postoperative week, and had less echogenic areas at the sixth
      postoperative week. Histological evaluation showed that Z-plasty had
      significantly more formation of fibrosis and adhesion and less parallel
      homogeneous collagen fibres at the sixth postoperative week (p<0.05). U-T plasty
      had a significantly higher mean (SD) failure load (15.35 (1.89) N) than the other
      two methods during the third postoperative week (p<0.05). There was no
      significant difference in failure load between the groups at the sixth
      postoperative week. U-T plasty is a good alternative to Z-plasty technique for
      lengthening tendons, and it may be the first choice in those who need moderate
      lengthening of tendons and early rehabilitation because it is easy to do, heals
      better, and has good biomechanical properties.

PMID- 19153876
TI  - Jack-like eversion by splitting the orbicularis oris muscle for reconstruction of
      the philtral column in secondary cleft lip.
AB  - The philtrum is an important aesthetic unit that contributes hugely to the
      characteristics of the human face. From March 2002 to May 2006 inclusive, a total
      of 16 patients with unilateral cleft lip nose were operated on to form a philtral
      column and obtain muscular continuity. Six of the patients were female and 12
      were male, age range 5 to 30 years old. We used Millard's method, so rotation and
      advancement flaps were planned. A full thickness incision was made down to the
      orbicularis oris muscle and mucosa after the scar on the philtral column had been
      excised. The medial and lateral muscle flaps were exposed and split into two
      leaves at the coronal plane. The deepest part of the muscle flaps were sutured
      together to create a jack-like eversion. Skin and mucosa were then closed. The
      follow-up period ranged from 8 to 18 months (mean 11 months). Two visual analogue
      scales were used to assess the outcomes. Thirteen of 16 patients were satisfied
      with their good result. Three had moderate results. The advantages of the
      technique are: ease of use; the creation of an anatomically-natural philtrum
      while preserving the continuity and function of the muscle; sufficient
      augmentation of the philtral column by the jack-like eversion; and no donor-site
      morbidity.

PMID- 19153877
TI  - Extension or combination of an autologous latissimus dorsi flap in breast
      reconstruction.
AB  - The lateral thoracodorsal flap and the pedicled latissimus dorsi flap have been
      extensively described for breast reconstruction. In search of an alternative, non
      microsurgical, autologous method of breast reconstruction we used both flaps
      combined to achieve adequate volume. The technique was used on three patients who
      had had a mastectomy at least two years previously. All flaps healed uneventfully
      with the appearance of an ordinary latissimus dorsi breast reconstruction. The
      method shows promising initial results and can be used as an alternative when
      reconstruction with autologous tissue is preferred.

PMID- 19153878
TI  - Endoscopic and ultrasonic removal of a lipoma on the forehead with no facial
      scarring: practicality of patient's early return to work.
AB  - We used endoscopy and ultrasonic liposuction to remove lipomas from the forehead
      to facilitate early return to work. The tumours were approached through a pair of
      small remote scalp incisions behind the frontal hairline, which continued to
      subperiosteal dissection, thereby avoiding injury to the supraorbital or
      supratrochlear neurovascular bundles. The deep surfaces of the lipomas were
      identified easily through the periosteum by well-illuminated and magnified
      endoscopic views, and protruded through the periosteal incisions. An ultrasonic
      cannula was introduced to emulsify and aspirate the lipomas. Parts of the lipomas
      were extracted by forceps as solid specimens for histopathological evaluation.
      Preservation of the neurovascular bundles and complete resection of the tumours
      in the bloodless operative fields were confirmed by direct endoscopic monitoring.
      Of five patients treated, three returned to their jobs within two postoperative
      days, with no protective dressings on their faces. There have, to our knowledge,
      been few reports describing this combination of endoscopy and ultrasonic
      treatment of forehead lipomas.

PMID- 19153879
TI  - Surgical correction of cryptotia with the square flap method: a preliminary
      report.
AB  - Cryptotia is the fourth most common congenital auricular deformity, and it is
      more prevalent among Asians. A number of techniques for its correction have been
      introduced, and relatively favourable results have been achieved. We describe our
      experience with a technique for its correction using the square flap method
      designed on the temporal scalp and skin over the auricle. From 2001 to 2006 a
      total of 19 examples in 12 patients were treated. Seven patients had bilateral,
      and five had unilateral, cryptotia. Traction was applied to the upper part of the
      auricle to draw it away from the scalp, and the square flap method, consisting of
      two triangular flaps and one square flap, were designed on the temporal scalp and
      skin over the auricle. After the skin had been incised, the three flaps were
      freed completely, and the abnormal insertion of the auricular intrinsic muscles
      was detached. The flaps were then transposed, advanced, and sutured. There were
      no problems of viability in any patient, and all healed well. The follow-up
      period was 3 months to 2 years, with relatively favourable results. Function and
      appearance were satisfactory in all patients. The length of the helix was
      extended, and it was possible to increase the width of the upper part of the
      auricle. This technique is indicated in cases of mild to moderate cryptotia, and
      has many advantages, including simple and easy design, provision of enough skin
      for the upper and posterior portions of the auricle, sufficient depth of the
      auriculocephalic sulcus, and no additional skin grafting.

PMID- 19153880
TI  - Immunohistochemical evidence for Zic1 coexpression with beta-catenin in the
      myofibroblast of Dupuytren disease.
AB  - The active cellular component in Dupuytren disease (DD) is the alpha-smooth
      muscle actin (alpha-SMA) containing myofibroblast. The underlying regulatory
      processes in activation of myofibroblasts resemble the pathophysiology of certain
      types of cancer. Accumulation of beta-catenin has been shown in many
      fibroproliferative processes, including DD and, recent findings attributed a
      possible role to the Zic1 transcription factor. To assess Zic1 expression in DD
      and investigate its relation with the accumulation of beta-catenin, neighbouring
      tissue samples in 20 patients with DD were stained immunohistochemically with
      monoclonal antibodies for beta-catenin, alpha-SMA, and Zic1. Histological
      appearance was staged according to Luck. Cell-rich areas with accumulation of
      beta-catenin in myofibroblasts that stained for alpha-SMA and showed apparent
      Zic1 coexpression were obvious. This coexpression seemed independent of
      proliferative or involutional histological staging. We found only Zic1 expression
      in residual stages. A different pattern of expression of protein in the residual
      stage may support earlier suggestions of a cellular heterogeneity with the
      existence of different cell (sub-)populations in nodules and cords. On the other
      hand coexpression of Zic1 and beta-catenin may indicate a relation between Zic1
      and the Wnt-pathway. Further studies are needed to elucidate cellular origin,
      potential heterogeneity and activity of the myofibroblasts in DD, and to define
      the exact role of Zic1 in fibroproliferative processes, wound healing, and
      cancer. The fibroblast in DD is an interesting model for future experiments.

PMID- 19153881
TI  - Effect of severity of Dupuytren contracture on disability.
AB  - The aim of this study was to investigate the correlation between the severity of
      Dupuytren contracture and disability. The American Medical Association (AMA)
      guidelines were used to assess the impairment for each involved hand. The
      disability of the arm, shoulder and hand (DASH) questionnaire was used for
      evaluating the disability. Eighty patients with 102 involved hands were enrolled.
      The mean total flexion contracture was 119 degrees /hand or 65 degrees /ray. The
      mean DASH score was 15 (range 0-69). There was no significant correlation between
      the DASH score on one hand and the total flexion contracture, the mean flexion
      contraction/finger, the mean flexion contracture of the proximal interphalangeal
      (PIP), the mean flexion contracture of the metacarpophalangeal (MCP), the number
      of involved hands, fingers or joints, and the AMA impairment rating on the other
      hand.

PMID- 19153882
TI  - Tumours of peripheral nerves in the upper extremity: a 22-year epidemiological
      study.
AB  - Peripheral nerve tumours are uncommon. Our aims were to calculate the incidence
      and relative frequencies, to define sites of nerve tumours and to judge
      preoperative symptoms and outcomes of intervention. The results of 53 patients,
      with 68 tumours and histopathological diagnoses of true neoplasms, who had been
      operated on at the Department of Hand Surgery, Malmo, Sweden, between 1986 and
      2007, were analysed. Schwannomas were the most common tumour (n=42). The
      incidence of schwannomas was 0.62/100 000 inhabitants/year in Malmo during that
      time period. The median nerve was most affected, closely followed by the ulnar
      and digital nerves. The preferred sites were the forearm, the thumb, and the
      digits. The most common preoperative symptom was pain. Loss of sensation was the
      most common postoperative complication. However, 33/53 patients (62%) were
      completely free of symptoms after excision. Patients should be provided with
      meticulous information preoperatively.

PMID- 19153884
TI  - Reconstruction of adult auricular defect with thin titanium mesh and prelaminated
      free radial forearm flap.
AB  - We used a thin titanium mesh combined with a prelaminated free radial forearm
      flap to construct a framework to reconstruct a traumatic defect in an adult ear.
      The prelaminated forearm flap covered both the anterior and posterior aspects of
      the titanium framework. A raised ear could therefore be created.

PMID- 19153883
TI  - Aetiology and treatment of a previously denervated "tennis" elbow.
AB  - The aetiology of the "tennis" elbow is still disputed and treated by numerous
      different operations. We report 24 patients with treatment-resistant, previously
      denervated epicondylitis. The revision consisted of complete decompression of the
      radial nerve from the lateral intermuscular septum to beyond the arcade of Frohse
      in 24 patients using an anterolateral access. There was a mean period of 31 (10)
      months between the onset of the condition and the revision. Compared with the
      preoperative findings, there were improvements in 19 of the 24 patients, with
      four patients remaining unchanged, and one patient deteriorating. If the
      condition has been resistant to treatment for some time, complete decompression
      of the radial nerve is an effective option with few complications compared with
      further operation on the epicondyle.

PMID- 19153885
TI  - Compartment syndrome in the forearms of two neonates.
AB  - Two neonates with proximal dorsal swelling and skin necrosis had median, ulnar,
      and particularly radial nerve palsies after birth, which was interpreted as
      compartment syndrome in the forearm. The swelling in case 1 disappeared, the skin
      lesion in case 2 healed, and the functions of nerves recovered almost completely
      in both cases, although the forearm and hand in the second patient were shorter
      and thinner than the contralateral side.

PMID- 19153886
TI  - What to do with non-replanted hands?
AB  - We describe a method for the preparation of amputated limbs to obtain a specimen
      for anatomical study of the arteries and the skeleton. The procedure is
      particularly applicable to hands, and prevents the destruction of a perfect hand
      that cannot be replanted.

PMID- 19153887
TI  - Rates of sickness certification in European primary care: a systematic review.
AB  - BACKGROUND: General practitioners (GPs) are responsible for assessing a patient's
      capacity for work and issuing a sickness certificate, enabling a patient to
      receive statutory sick pay and take time away from the workplace. The management
      of sickness absence across Europe varies considerably, and there is a need for
      comparable rates of certification to facilitate appropriate health and economic
      planning. OBJECTIVE: To systematically review the literature reporting rates of
      sickness certification in general practice settings. METHODS: Electronic
      databases were searched from their inception to November 2007. Inclusion criteria
      were reporting a measure of sickness certification, conducted in European primary
      care. RESULTS: 298 citations were identified from the literature search, of which
      11 met the inclusion criteria. These studies demonstrated that the rates of
      sickness certification are not routinely recorded. The certified rates were
      subject to wide variation, ranging from 18 per 100 person years in Norway to 239
      per 100 person years in Malta. CONCLUSION: There is large variability in sickness
      certification policy and hence sickness certification rates across Europe. A
      system that enables comparisons across countries would be beneficial in ensuring
      health and economic planning. To enable a baseline rate of certification to be
      established and compared across countries, standardized reporting of sickness
      certification is needed.

PMID- 19153888
TI  - Melatonin treatment of shoulder-and-neck dyskinesia possibly related to
      fluoxetine treatment.

PMID- 19153889
TI  - Interleukin-10 gene promoter polymorphism in patients with schizophrenia in a
      region of East Turkey.
AB  - Schizophrenia is one of the most severe psychiatric disorders, with a worldwide
      incidence of 1%. Immunological abnormalities have been found to be associated
      with schizophrenia for decades. Cytokines are key proteins involved in the immune
      system activation. Interleukin-10 (IL-10), an important immunoregulatory
      cytokine, is located on chromosome 1q31-32, a region previously reported to be
      linked to schizophrenia in genetic studies. In the present study it was aimed to
      examine the IL-10 gene promoter region's polymorphic variants in patients with
      schizophrenia in a population of the Elazig Region of East Anatolia, Turkey.
      Polymorphisms at position -1082, -819 and-592 in the IL-10 promoter region were
      determined in 171 Turkish patients who were diagnosed with schizophrenia, based
      on the DSM-IV, and 168 healthy controls, by polymerase chain reaction (PCR)
      restriction fragment length polymorphism (RFLP). We analyzed allele, genotype,
      and haplotype distributions using a case-control association study. Genotyping
      was performed by RFLP. Statistically significant differences were observed in
      both allelic and genotypic frequencies of the-592A/C polymorphism (Allele,
      P=0.034, OR = 1.26, 95% CI 1.02-1.56; Genotype, P=0.048), while the other two
      polymorphisms in distribution of the alleles and genotypes in patients with
      schizophrenia were not significantly different from those of controls (P>0.05).
      Our results show a significant increase of GTA homozygotes (the high IL-10
      producing haplotype) in schizophrenic patients compared to control subjects
      (P=0.0001). These data suggest that the IL-10 gene promoter polymorphism may be
      one of the susceptibility factors to develop schizophrenia in the Turkish
      population, and apparently in all humans.

PMID- 19153890
TI  - Alteration learning in social anxiety disorder: an fMRI study.
AB  - The present study attempts to challenge the orbitofrontal cortex by using a
      learning paradigm which is specifically subserved by this cortical region. We
      implemented a version of alternation learning specifically designed for fMRI and
      assessed the cognitive performance and fMRI response in wide range of social
      anxiety disorder (SAD) severity (n=15). The main regions that were activated by
      the alternation learning task included portions of frontal and orbitofrontal
      cortex as well as the calcarine fissure. Correlations between brain activation
      and performance of the alternation learning task were found, among other regions,
      in the left and right orbitofrontal cortex. Highest correlations between degree
      of activation and the anxiety scores as assessed by the Leibovitch Social Anxiety
      Scale (LSAS) were obtained in the left temporal region as well as orbitofrontal
      cortex. This study supports the involvement of the orbitofrontal cortex in
      emotion and cognitive regulation in SAD.

PMID- 19153891
TI  - Editorial.

PMID- 19153892
TI  - Poor medicine for poor people? Assessing the impact of neoliberal reform on
      health care equity in a post-socialist context.
AB  - Driven in part by a resurgent interest in social inequality and health, and in
      part by increasing scrutiny of the social and health consequences of neoliberal
      economic reform, principles of health equity and social justice, the centerpieces
      of the Health for All strategy drafted at Alma Ata in 1978, are once again at
      center stage in global public health debates. Whether and how equity in access to
      health care can be maintained in a context of market-based health sector reform
      has not been systematically addressed, particularly from the perspective of local
      communities. This paper will explore how health reform affects health care in
      post-socialist Mongolia. Through a mixed-methods household-based study of low-to
      middle income communities in urban and rural Mongolia we find that despite
      explicit and concerted efforts to reduce inequities, the reform system is unable
      to provide equitable health care either vertically or horizontally. Emphasis on
      privatization of the secondary and tertiary sectors of the system, coupled with
      deployment of universally-accessible, but from a clinical standpoint, limited,
      version of essential primary care, produces a fragmented system. Particularly for
      the vulnerable poor, access to services beyond the primary care system is
      compromised by financial, opportunity, and informational cost barriers. This
      research suggests that new models of health reform are needed that will
      effectively bridge the growing gaps between public and private resources, primary
      and secondary and/or tertiary care, and clinical and public health services.

PMID- 19153893
TI  - Beyond the Millennium Development Goals: public health challenges in water and
      sanitation.
AB  - Over 1 billion people lack access to improved water sources and 2.6 billion lack
      access to appropriate sanitation, greatly contributing to the global burden of
      disease. The international community has committed to reducing by half the
      proportion of the world's population lacking access to water and sanitation as a
      part of the Millennium Development Goals (MDGs). However, the disease burden due
      to poor access, is borne primarily by the poorest countries and the poorest
      people within them. Simply reducing the proportion of people without adequate
      access will not automatically result in proportional reductions in the related
      disease burden. The public health challenge inherent in meeting the MDG targets
      is ensuring that improvements result in access to water and sanitation for the
      critical at-risk populations. Innovative approaches are required to ensure the
      availability of low-cost, simple, and locally acceptable water and sanitation
      interventions and integrating these approaches into existing social institutions,
      such as schools, markets, and health facilities.

PMID- 19153894
TI  - Health systems and the implementation of disease programmes: case studies from
      South Africa.
AB  - This paper analyses the transfer and implementation of two internationally
      formulated infectious disease strategies in South Africa, namely, directly
      observed therapy (DOTS) for TB and syndromic management (SM) for sexually
      transmitted infections (STIs). Using the tools of policy analysis, this paper
      seeks to draw conclusions from contrasting experiences with the two strategies.
      DOTS and SM differ with respect to styles of engagement by World Health
      Organization (WHO), the international agency promoting the ideas, in the
      following ways: continuity and networking between policy makers, practitioners
      and researchers nationally; and approaches to sub-national implementation. We
      show how these factors may have been important to national uptake, and conclude
      on the need for a context sensitive approach to policy transfer and a balance
      between bottom-up and top-down implementation strategies. These insights may have
      relevance for the current global wave of treatment programmes for HIV and other
      infectious diseases.

PMID- 19153895
TI  - The global tobacco disease pandemic: nature, causes, and cures.
AB  - Tobacco use kills 5 million citizens globally every year. The World Health
      Organization (WHO) projects that the number of deaths will double just 15 years
      from now. Tobacco will then constitute the leading cause of death in the
      developing world, as it already is in developed countries today. This paper
      describes the nature and extent of the tobacco pandemic, characteristics of the
      global tobacco industry, and national and international efforts to diminish the
      toll of tobacco. The review includes examination of the economic and political
      strategies employed by the multinational tobacco industry to increase cigarette
      consumption, as well as the policies that governments have adopted to combat
      smoking. The most promising development is the new Framework Convention on
      Tobacco Control, WHO's first-ever international health treaty. While aggressive
      tobacco control policies can and will diminish the toll of tobacco, the prospects
      for the foreseeable future appear grim.

PMID- 19153900
TI  - The next two issues of Global Public Health are devoted to articles related to
      public health in both natural and man-made emergencies. Editorial.

PMID- 19153896
TI  - Mozambique child soldier life outcome study: lessons learned in rehabilitation
      and reintegration efforts.
AB  - As the use of child soldiers continues to proliferate throughout the world,
      effective psychosocial interventions must be developed and evaluated. Our
      research shows that former child soldiers who are provided rehabilitative
      services and accepted back into their families and communities are able to become
      productive, responsible and caring adults. In 1988, 39 captured or escaped child
      soldiers were brought by the Mozambican government to the Lhanguene
      Rehabilitation Center in Maputo, Mozambique's capital city. Interventions that
      focused on rehabilitating the children both psychologically and physically were
      initiated during their 6-month stay at the Lhanguene centre, and reintegration
      assistance was provided for 2 years thereafter to support their return to
      families and communities. Our research continued to follow these former child
      soldiers for 16 years, and focused on their psychological, social and economic
      functioning. The study included qualitative and quantitative data collection
      methods to obtain adult well-being outcomes and was also designed to identify
      interventions that enabled these child soldiers to re-enter civilian life and
      lead relatively productive lives. Efficacious rehabilitation activities included
      those that strengthened individuals' coping skills for anticipated trauma and
      grief, instilled a sense of social responsibility and promoted self-regulation
      and security (versus survival) seeking behaviour. Activities that supported long
      term reintegration and self-sufficiency included community acceptance and
      forgiveness, traditional cleansing and healing rituals, livelihoods and
      apprenticeships.

PMID- 19153901
TI  - Child survival during the 2002-2003 drought in Ethiopia.
AB  - Droughts in Ethiopia have commonly been associated with increased child
      mortality. Early indications were that the 2002/03 drought, which affected 13.2
      million people, was no exception, despite a large relief operation. Humanitarian
      agencies reported sharp increases in child deaths and pockets of acute distress
      in some hard-hit localities. In response, the 2004 Ethiopia Child Survival Survey
      (ECSS) was designed to investigate the impact of the drought on child survival in
      the general population. The survey covered 4816 households in both drought
      affected and non-drought affected, as well as rural and urban localities. Data
      from the ECSS indicate that child mortality was indeed higher in drought-affected
      areas. However, a closer analysis reveals that this differential is attributable
      to chronic conditions in those localities, rather than the immediate impact of
      the 2002/03 drought. Multivariate analysis was used to construct a model for the
      determinants of child survival in the sample population. Household-level
      demographic factors, household-level food and livelihood security, community
      level economic production, and access to potable water, were predictive of child
      survival. Additionally, household receipt of food aid had a small but significant
      positive association with child survival, even though the ECSS cannot determine
      either the underlying causal mechanisms of this association or the role of
      confounding factors. Nonetheless, it is remarkable that the most extensive
      drought in the country's modern history passed without a measurable increase in
      child mortality among the general population. Yet Ethiopian children still suffer
      unacceptably high rates of chronic malnutrition and poor life chances, and large
      populations continue to live at the brink of destitution and calamity.

PMID- 19153902
TI  - Addressing sexual violence in humanitarian emergencies.
AB  - Sexual violence is a by-product of conflict commonly seen, but poorly addressed,
      in humanitarian emergencies. Reports reveal that extraordinary numbers of women
      and girls suffer physical, psychological, and social consequences of sexual
      violence during conflict, when fleeing conflict, and during displacement. All
      sectors of the humanitarian community have a role to play in the prevention of
      and response to sexual violence. Improvements are needed: in the short-term to
      meet the needs of survivors of sexual violence; in collecting data related to
      sexual violence in humanitarian emergencies; and, perhaps most importantly, to
      address the widespread tolerance for high rates of sexual violence in
      humanitarian settings.

PMID- 19153903
TI  - HIV behavioural surveillance surveys in conflict and post-conflict situations: a
      call for improvement.
AB  - Behavioural surveillance surveys (BSSs), an evolution from the knowledge
      attitudes-practice surveys (KAPs), are a tool to track trends in HIV/AIDS
      knowledge, attitudes and risk behaviour among populations. The data collected
      support organizations in targeting specific HIV/AIDS prevention and care
      activities, monitoring their effectiveness and coverage, and allocating scarce
      resources. The objectives are to evaluate the quality and standardization of BSS
      like surveys undertaken in conflict and post-conflict situations, and to provide
      recommendations to humanitarian agencies and governments on how to improve their
      quality. Survey methodology was classified as reproducible if the population
      based sampling defined a sampling frame using probabilistic sampling. Survey
      indicators were compared to internationally-accepted HIV indicators. The results
      showed that 14 (45.2%) of the 31 BSS-like surveys evaluated between 1998 and 2005
      in 14 countries were classified as reproducible. Surveys undertaken by non
      governmental organizations (NGOs) were significantly less reproducible than those
      undertaken by non-NGOs (p=0.05). The majority of surveys used at least one
      identical or similarly worded internationally-accepted HIV indicator for
      prevention and misperception but not for practice and attitudes. Few reported
      disaggregated indicators according to age or gender. It was concluded that the
      majority of BSS-like surveys are of insufficient methodological rigor to be
      reproducible. Few surveys reported internationally-accepted HIV indicators by
      gender and age which makes interpretability and comparison difficult. United
      Nations agencies, NGOs, and governments undertaking BSSs in conflict and post
      conflict settings should proceed with a BSS survey once the design and plan for
      execution has been prepared by experienced and qualified experts. These experts
      should then oversee the survey, assure data quality and incorporate training of
      others in the process. A practical and field user-friendly BSS manual is needed
      for conflict affected and displaced population situations, one which is
      customized to take into account the special circumstances of such populations.

PMID- 19153904
TI  - NGO management and health care financing approaches in the Eastern Democratic
      Republic of the Congo.
AB  - The role of cost-sharing in health care is a crucial, yet contentious issue. In
      conflict situations, cost-sharing becomes even more controversial as health and
      other institutions are failing. In such situations, NGOs manage health programmes
      which aim to aid populations in crisis and improve or at least sustain a
      deteriorating health system. This study looks at the issue of cost-sharing in the
      wider context of utilization rates and management approaches of three NGOs in the
      chronic, high-mortality crisis of the eastern DRC. Approaches to increase access
      to health care were found to exist, yet cost-recovery, even on the basis of
      maximum utilization rates, would only partially sustain the health system in the
      eastern DRC. Factors external to the direct management of NGO health programs,
      such as the wider economic and security situation, local management structures,
      and international donor policies, need to be taken into account for establishing
      more integrated management and financing approaches.

PMID- 19153906
TI  - Expert judgments of pandemic influenza risks.
AB  - Structured surveys were conducted with 19 medical experts, and 17 non-medical
      experts in related fields, attending a meeting about pandemic influenza.
      Respondents gave quantitative judgments for key variables potentially affecting
      the extent of a possible H5N1 pandemic. The medical experts saw about a 15%
      (median) chance of efficient human-to-human transmission, in the next 3 years.
      Should it occur, they saw almost no chance of there being adequate vaccines or
      antiviral responses. They saw varying chances of six other mitigation strategies
      reducing the threat, expressing the greatest faith in improved surveillance.
      Compared to the medical experts, the non-medical experts saw much higher chances
      of both human-to-human transmission and of effective vaccine and antiviral
      responses being available. The medical experts and the non-medical experts had
      similar, dire predictions for the extent of casualties, should transmission occur
      in the next 3 years. Their responses to open-ended questions revealed some of the
      theories underlying these beliefs.

PMID- 19153905
TI  - Outbreak of tetanus cases following the tsunami in Aceh Province, Indonesia.
AB  - Aceh Province in Indonesia was the area most severely affected by the tsunami of
      26 December 2004. Extensive loss of life, property, and livelihood left a large
      segment of the population without basic needs and vulnerable to epidemic-prone
      diseases. Following the tsunami, a surveillance/early warning and response system
      was implemented to detect, investigate, and respond to outbreaks of communicable
      diseases. Fixed and mobile clinics, hospitals, and laboratories, operating all
      over the affected areas, reported weekly figures and daily alerts. Over 1 month
      following the tsunami, 106 cases of clinically diagnosed tetanus were reported.
      Most cases occurred among adults. The case fatality ratio was 18.9%, higher among
      older patients and among those with short incubation periods. No other major
      outbreaks occurred in the acute phase of the emergency. This series of tetanus
      cases was the largest cluster reported following a natural disaster or mass
      casualty event, overtaken only by the recent earthquake in the Kashmir (139 cases
      reported), and reflects the high number of injuries which occurred during the
      tsunami and poor prior immunization status of the population. In the context of
      natural disasters, preventive measures against tetanus, including wound cleaning
      and active and passive immunization, should be routinely conducted. Immediate
      disaster relief should include supplies for the management of wounds and cases of
      tetanus.

PMID- 19153907
TI  - High mortality in an internally displaced population in Ituri, Democratic
      Republic of Congo, 2005: results of a rapid assessment under difficult
      conditions.
AB  - The ongoing conflict in Ituri, Democratic Republic of Congo (DRC), has led to
      more than 50,000 deaths, more than 500,000 displaced civilians and continuing,
      unacceptably high, mortality since 1999. In February 2005, after a resurgence of
      violence and further displacements, Medecins Sans Frontieres (MSF) launched an
      emergency response in three internally displaced persons (IDP) camps in Ituri. We
      performed a rapid health assessment in April 2005 in one of the IDP camps to
      evaluate mortality (due to violence or disease) and camp living conditions. The
      retrospective mortality survey, covering a recall period from 18 December 2004 to
      27 March 2005, indicated a crude mortality rate of 4.1 deaths/10,000/day (95% CI:
      2.8-5.4) and an under-five mortality rate of 6.9 deaths/10,000/day (95% CI: 4.4
      9.4). Living conditions in the camp were extremely poor (average 286 persons per
      latrine). Despite efforts of the international community and humanitarian
      organizations, the security situation continues to deteriorate. Regular
      assessments should be undertaken to monitor the situation.

PMID- 19153908
TI  - Improving the availability of emergency obstetric care in conflict-affected
      settings.
AB  - This paper describes an emergency obstetric care (EmOC) project implemented by
      the Reproductive Health Response in Conflict (RHRC) Consortium in 12 conflict
      affected settings in nine countries from 2000-2005 with funding and technical
      support from Columbia University's Mailman School of Public Health Averting
      Maternal Death and Disability (AMDD) programme. The overall goal of the project
      was to reduce maternal morbidity and mortality in select conflict-affected
      settings by improving the availability of EmOC. Another aim of the project was to
      institutionalize EmOC within RHRC Consortium agencies by modelling how to improve
      the availability of basic and comprehensive EmOC at clinics and hospitals. The
      specific project purpose was to increase the availability of EmOC in select
      conflict-affected settings. The project demonstrated that a great deal more can
      and should be done by humanitarian workers to improve the availability of basic
      and comprehensive emergency obstetric services in conflict-affected settings.

PMID- 19153909
TI  - Improving refugees' reproductive health through literacy in Guinea.
AB  - Adult literacy programmes, particularly literacy-for-health programmes that
      integrate health material in their curricula, are gaining momentum as a means to
      improve women's and children's health and increase women's empowerment. However,
      the relationship between literacy skills and these benefits remains unclear. This
      paper presents results from a study on the Reproductive Health Literacy (RHL)
      Project among Sierra Leonean and Liberian women in refugee camps in Guinea.
      Literacy classes met for 2 hours twice per week for 6 months, with content
      focused on safe motherhood, family planning, STIs/HIV/AIDS and gender-based
      violence. A closed-ended interview and a written test of literacy skills were
      administered to 549 former RHL students to understand the programme's effects.
      Results indicate that participants had a high level of reproductive health
      knowledge after participation, and reported an increase in literacy skills.
      Respondents' current use of modern contraception was 48%, of which 23% reported
      using a condom at last sex. Findings suggest an increase from reported pre-RHL
      behaviour. Participants also reported a dramatic increase in 'boldness', the
      phrase used to describe empowerment. While only a third (32%) of respondents
      considered themselves 'more bold' than other women before RHL, a clear majority
      (82%) so considered themselves after RHL. A comparison of schooled and unschooled
      women indicates that those who had had previous schooling did better in RHL than
      their non-schooled colleagues, but both groups had good knowledge retention,
      positive behaviour levels and felt more bold after RHL participation.

PMID- 19153910
TI  - Changes in HIV/AIDS/STI knowledge, attitudes, and behaviours among the youth in
      Port Loko, Sierra Leone.
AB  - Sierra Leone suffered from 11 years of civil war (1991-2002) resulting in tens of
      thousands of deaths and mutilations and massive population displacement. In 2001,
      ARC International, Sierra Leone, conducted a baseline survey of 244 female youth
      and 293 male youth on knowledge, attitudes, and behaviours around HIV/AIDS and
      STIs in Port Loko. In 2003, following 2 years of HIV prevention activities, a
      comparable post-intervention survey of 250 female and 299 male youth was
      performed. Comparison of baseline and post-intervention results showed that
      HIV/AIDS knowledge increased dramatically among both groups, with those able to
      name three effective means of avoiding AIDS increasing from 4% to 36% among
      female youth, and 4% to 45% among male youth. Reported condom use at last sex
      increased among female youth from 16% to 46% and among male youth from 16% to
      37%. These results demonstrate that, despite the challenges inherent in a post
      conflict country, good quality AIDS prevention programmes can be successful.

PMID- 19153911
TI  - Placing ethics in the centre: negotiating new spaces for ethical research in
      conflict situations.
AB  - Issues of power and consent, confidentiality, trust, and benefit, risks to
      researchers, and potential harm to participants, are all contested when working
      with different cultures and within environments marked by violence and
      insecurity. Difficulty resolving these dilemmas may paralyse ethics committees,
      may fail to give the guidance sought by researchers, and will not help
      populations who are among the world's most vulnerable. Even where efforts are
      made to respond to ethical guidelines and to improve practice, considerable
      impediments are present in many developing countries, including lack of formal
      ethical review structures in unstable settings, lack of required skills, limited
      political and institutional recognition of ethical issues, competing interests,
      and limitations in clinical and research practice (Elsayed 2004, Macklin 2004).
      In conflict settings, these limitations are more marked, and the responsibilities
      of the researcher for ethical practice are greater, but the mechanisms for
      oversight are weaker. Moreover, the constant focus on vulnerabilities and
      problems, and the often almost total lack of recognition of strengths and
      resilience, can further disempower already exploited groups and individuals. The
      capacity of refugees and communities in conflict to take an active role in the
      research process is seldom acknowledged, and undermines the potential for more
      innovative research which can help generate the evidence for better policy and
      practice.

PMID- 19153916
TI  - Relapse of successfully treated anxiety and fear: theoretical issues and
      recommendations for clinical practice.
AB  - Despite the existence of effective interventions for anxiety disorders, relapse-
      or the return of fear--presents a significant problem for patients and clinicians
      in the longer term. The present paper draws on the experimental and clinical
      behavioural literature, reviewing the mechanisms by which the return of fear can
      occur. The aim of the paper was to generate a list of treatment recommendations
      for clinicians aimed at reducing relapse in successfully treated anxiety
      disorders. Clinical and experimental literature on the mechanisms of renewal,
      reinstatement, spontaneous recovery and reacquisition are reviewed. These are
      linked with the clinical and experimental literature on the return of fear in
      successfully treated anxiety. A list of recommendations to assist in reducing the
      probability of relapse in successfully treated anxiety is presented. This list
      includes methods for use in behavioural (exposure) treatment of anxiety disorders
      that aim to enhance clinical outcomes. Despite the significant problem of relapse
      in successfully treated anxiety, there are methods available to reduce the
      probability of relapse through return of fear. Clinicians engaging in treatment
      of anxiety disorders should be mindful of these methods to ensure optimal patient
      outcome.

PMID- 19153917
TI  - Dopamine vs noradrenaline: inverted-U effects and ADHD theories.
AB  - The aim of the present study was to review the dopamine theory of attention
      deficit-hyperactivity disorder (ADHD), in light of recent use of noradrenergic
      therapies. A historical review of pharmacological theories of ADHD was conducted,
      including inverted-U, spatial working memory and neural circuit aspects.
      Pharmacological advances, including animal and human studies of dopaminergic and
      noradrenergic mechanisms at the prefrontal cortex (PFC), indicate that alpha-2A
      adrenoreceptor stimulation results in increased dendritic firing during delay
      periods for preferred directions, while moderate levels of D1 receptor
      stimulation result in reduction of delay-related firing to non-preferred
      directions, allowing representational control in the PFC. Recent studies of the
      COMT val/met gene and stimulant medication response may help explain variation in
      inverted-U responses in individuals. Further studies utilizing delay-related
      firing paradigms should be useful in the investigation of attentional syndromes,
      and responses to newer pharmacological treatments.

PMID- 19153918
TI  - Characteristics of bipolar disorder in an Australian specialist outpatient
      clinic: comparison across large datasets.
AB  - OBJECTIVES: There have been relatively few detailed reports on the
      sociodemographic and clinical characteristics of bipolar disorder in large
      outpatient clinical samples. This paper reports on findings from the Black Dog
      Institute Bipolar Disorders Clinic (BDI-BDC) and compares this dataset with the
      predominantly outpatient Stanley Foundation Bipolar Disorders Network (SFBN) and
      Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) samples.
      METHODS: A total of 217 patients with DSM-IV bipolar disorder were assessed in
      detail in the BDI-BDC using a series of standardized and non-standardized
      structured interviews. Ninety per cent had bipolar I disorder, and 10% bipolar II
      disorder. This sample was compared with the SFBN and STEP-BD datasets. RESULTS:
      The sociodemographic characteristics of the three samples were remarkably
      similar. Female gender and younger age were overrepresented compared to the
      general population. Functional impairment, indicated by marital status and labour
      force participation, was clearly more common among the study subjects than in the
      general population. In all three samples, prior educational attainment was higher
      than the general population. With respect to clinical features, approximately
      half of each sample was euthymic and approximately one-third was in a DSM-IV
      episode of depression at study entry. One-half reported depression as their first
      episode of mood disturbance. Similar proportions identified positive family
      histories of bipolar disorder (40%) and unipolar depression (55%). Other clinical
      characteristics demonstrated more variation between the samples. The STEP-BD
      population reported an earlier age of onset. The SFBN subjects reported higher
      numbers of overall episodes, but psychotic features and suicide attempts were
      less common than in the BDI-BDC sample. CONCLUSIONS: This report highlights the
      marked commonalities of the sociodemographic and clinical characteristics of
      patients with bipolar disorder recruited predominantly in the outpatient setting
      in three different continents, that is, Australia, North America and Europe. It
      also demonstrates some critical distinctions between such samples, emphasizing
      the need to be aware of these differences when interpreting findings, such as
      treatment outcome, from different bipolar disorder datasets.

PMID- 19153919
TI  - Psychotic-like experiences in a community sample of adolescents: implications for
      the continuum model of psychosis and prediction of schizophrenia.
AB  - OBJECTIVE: Studies conducted in community samples suggest that psychotic-like
      experiences are common in the general population, leading to suggestions that
      they are either variations of normal personality or are different expressions of
      underlying vulnerability to psychotic disorder. Different types of psychotic
      symptoms may exist, some being normal variants and some having implications for
      mental health and functioning. The aim of the present study was to determine if
      different subtypes of psychotic-like experiences could be identified in a
      community sample of adolescents and to investigate if particular subtypes were
      more likely to be associated with psychosocial difficulties, that is, distress,
      depression and poor functioning, than other subtypes. METHOD: Eight hundred and
      seventy-five Year 10 students from 34 schools participated in a cross-sectional
      survey that measured psychotic-like experiences using the Community Assessment of
      Psychic Experiences; depression using the Centre for Epidemiologic Studies
      Depression Scale; and psychosocial functioning using the Revised Multidimensional
      Assessment of Functioning Scale. Factor analysis was conducted to identify any
      subtypes of psychotic experiences. RESULTS: Four subtypes of psychotic-like
      experiences were identified: Bizarre Experiences, Perceptual Abnormalities,
      Persecutory Ideas, and Magical Thinking. Intermittent, infrequent psychotic
      experiences were common, but frequent experiences were not. Bizarre Experiences,
      Perceptual Abnormalities and Persecutory Ideas were strongly associated with
      distress, depression and poor functioning. Magical Thinking was only weakly
      associated with these variables. Overall these findings may suggest that
      infrequent psychotic-like experiences are unlikely to be a specific risk factor
      for onset of a psychotic disorder in community samples. CONCLUSIONS: Given that
      the different subtypes had varying associations with current difficulties it is
      suggested that not all subtypes confer the same risk for onset of psychotic
      disorder and poor outcome. Bizarre Experiences, Perceptual Abnormalities and
      Persecutory Ideas may represent expressions of underlying vulnerability to
      psychotic disorder, but Magical Thinking may be a normal personality variant.

PMID- 19153920
TI  - Coronary heart disease risk reduction intervention among overweight smokers with
      a psychotic disorder: pilot trial.
AB  - OBJECTIVE: The aim of the present pilot study was to test the feasibility and
      short-term impact of a multi-component risk factor intervention for reducing (i)
      coronary heart disease (CHD) risk; (ii) smoking; and (iii) weight among smokers
      with psychosis. Secondary dependent variables included physical activity,
      unhealthy eating, substance use, psychiatric symptomatology, treatment retention,
      general functioning, and quality of life. METHOD: This was a feasibility study
      utilizing a pre-post-treatment design with no control group (n=43). All
      participants provided written informed consent and were assessed before treatment
      and again a mean of 19.6 weeks later. The treatment consisted of nine individual
      1h sessions of motivational interviewing and cognitive behaviour therapy plus
      nicotine replacement therapy, in addition to treatment as usual. Research
      assistants who had not been involved in the delivery of the treatment programme
      conducted post-treatment assessments. RESULTS: The intervention was associated
      with significant reductions in CHD risk scores, smoking and weight. A significant
      improvement was also reported in level of moderate physical activity, and a small
      change in the unhealthy eating index was reported. No improvement in biological
      measures (cholesterol and blood pressure) was evident. CONCLUSIONS: A multi
      component CHD risk factor intervention among smokers with psychosis appears to be
      feasible and effective in the short-term. A randomized controlled trial
      replicating and extending these findings is warranted.

PMID- 19153921
TI  - Psychiatric illness among a nationally representative sample of sole and
      partnered parents in New Zealand.
AB  - OBJECTIVE: To quantify the excess risk of specific, diagnosable mental illnesses
      experienced by sole parents in New Zealand, and to estimate the contribution of
      socioeconomic position (SEP), co-residence with other adults (as a proxy for
      social and practical support) and physical health status to this excess risk.
      METHODS: Data used in the present study were from the New Zealand Mental Health
      Survey, a nationally representative population-based household survey of 12,992
      adults (16+ years) fielded in 2004. The sample included 1216 sole and 3681
      partnered parents living with one or more dependent children, with an overall
      response rate of 73%. Mental illness (12 month prevalence of anxiety, mood, and
      substance use disorders, and suicidality) was measured with version 3.0 of the
      Composite International Diagnostic Interview. Illness severity was measured with
      the Sheehan Disability Scale and the Global Assessment of Functioning Scale.
      Covariates included household income from all sources, labour market attachment,
      co-residence with other adults and doctor-diagnosed chronic physical illness.
      Multiple logistic regression was then carried out on the weighted cross-sectional
      survey dataset. RESULTS: Adjusting for demographic variables, sole parents had
      significantly higher 12 month prevalences of mental illnesses than their
      partnered counterparts, with odds ratios (ORs) of 2.6 (95% confidence interval
      (CI)=2.0-3.3) for any mental illness, 2.9 (95%CI=2.1-4.0) for any serious mental
      illness, 2.2 (95%CI=1.7-2.8) for anxiety disorder, 2.6 (95%CI=2.0-3.4) for mood
      disorder, 3.6 (95%CI=2.2-6.0) for substance use disorder and 2.5 (95%CI=1.5-4.0)
      for suicidal ideation. Chronic physical illness accounted for only a small
      proportion of these excess risks. SEP and co-residence of another adult each
      explained approximately one-quarter of the excess risks and jointly explained
      approximately half (except for substance use disorders). Almost all of the effect
      of SEP was mediated by income, with employment status making only a very small
      independent contribution. CONCLUSIONS: The present results confirm the higher
      prevalence of mental illness experienced by sole parents, underlining the
      importance of improving access to primary mental health care, including alcohol
      and drug rehabilitation services, for sole parents. But they also caution against
      a solely clinical response and highlight a need to better understand and respond
      to the social and economic processes that lie behind the associations between
      mental health, socioeconomic position and sole parenthood in New Zealand.

PMID- 19153922
TI  - Personality differences between depressed melancholic and non-melancholic
      inpatients.
AB  - OBJECTIVE: The aim of the present study was to confirm that non-melancholic
      depression corresponds to a higher degree of personality dysfunction compared to
      melancholia. METHOD: A total of 188 inpatients, with a main DSM-IV diagnosis of
      major depressive disorder, were classified as melancholic and non-melancholic
      according to CORE system, DSM-IV, Research Diagnostic Criteria (RDC) Retarded
      Depression, and RDC Agitated Depression. Personality was assessed by means of the
      Temperament and Personality Questionnaire (T&P). Only patients at the nadir of
      their episode were included. RESULTS: Compared to non-melancholic depressives,
      patients with CORE melancholia scored lower on social avoidance and higher on
      effectiveness and cooperativeness; patients with RDC Retarded Depression scored
      lower on Anxious-Worrying and Cooperativeness; patients with RDC Agitated
      Depression scored lower on Social Avoidance, Rejection Sensitivity and Anxious
      Worrying, and higher on Effectiveness; while patients with DSM-IV melancholia
      scored higher on Irritability and lower on Cooperativeness. Both CORE and RDC
      Agitated Depression were associated with higher scores of Perfectionism.
      CONCLUSIONS: The hypothesis of an association of melancholic depression with less
      marked personality dysfunction was confirmed for CORE melancholia and RDC
      Agitated Depression, and not supported for DSM-IV melancholia. Mixed evidence was
      obtained for RDC Retarded Depression. Personality of melancholic depressives
      seems to be characterized not only by less dysfunction but also by perfectionism,
      akin to the features of Tellenbach's typus melancholicus.

PMID- 19153923
TI  - Prevalence and predictors of suicide attempt in an incidence cohort of 661 young
      people with first-episode psychosis.
AB  - OBJECTIVES: Studies investigating suicidal behaviour in psychosis rarely focus on
      incidence cohorts of first-episode patients. This is important, because patients
      who refuse study participation have higher rates of comorbid substance use
      disorders and longer duration of untreated psychosis as well as worse course
      illness, variables potentially linked to higher prevalence of suicidal behaviour.
      The aims of the present study were therefore to examine the prevalence and
      predictors of suicide and suicide attempt before and during the first 18-24
      months of treatment. METHOD: A retrospective file audit of 661 patients was
      carried out. RESULTS: Six patients (0.9%) died by suicide, 93 (14.3%) attempted
      suicide prior to entry, and 57 (8.7%) did so during treatment. Predictors of
      suicide attempt were: previous attempt (odds ratio (OR)=45.54, 95% confidence
      interval (CI)=9.46-219.15), sexual abuse (OR=8.46, 95%CI=1.88-38.03), comorbid
      polysubstance (OR=13.63, 95%CI=2.58-71.99), greater insight (OR=0.17, 95%CI=0.06
      0.49), lower baseline Global Assessment of Functioning Scale and Scale of
      Occupational and Functional Assessment score (OR=0.96, 95%CI=0.62-0.91; OR=0.98,
      95%CI=0.95-0.99), and longer time in treatment (OR=1.05, 95%CI=1.03-1.08).
      CONCLUSIONS: The prevalence of suicidal behaviour was high, indicating that
      suicidal behaviour in incidence populations is higher than in non-epidemiological
      cohorts of first-episode patients. The rate of repetition of suicide attempt
      among the sample, however, was lower than expected, suggesting that specialist
      services can play a role in reducing suicide risk.

PMID- 19153924
TI  - Lifetime prevalence of suicidal ideation, suicide plans and attempts in rural and
      urban regions of Beijing, China.
AB  - OBJECTIVE: There has been no large-scale survey of suicide-related behaviours
      including suicidal ideations, plans and attempts in China involving both rural
      and urban areas and using standardized assessment tools. The aim of the present
      study was to determine the lifetime prevalence of suicide-related behaviour and
      its relationship with sociodemographic factors and psychiatric disorders in the
      rural and urban regions of Beijing, China. METHODS: A total of 5926 subjects were
      randomly selected in Beijing and interviewed using the Composite International
      Diagnostic Interview. Basic sociodemographic and clinical data and data on
      suicide-related behaviour were also collected. RESULTS: The overall lifetime
      prevalence estimates of suicidal ideation, plans and attempts were 2.3%, 1.4%,
      and 1.0%, respectively; the corresponding figures were 2.8%, 1.6%, and 1.3% in
      the rural sample, and 1.8%, 1.3%, and 0.9% in the urban sample. Age (>25 years),
      female sex, unmarried status, lower education level, lower (<RMB500 month(-1)) or
      higher (>RMB2000 month(-1)) monthly income and presence of major medical
      disorders were significantly associated with increased risk of suicide-related
      behaviour. 36.2% of subjects with suicide-related behavior consulted a medical
      practitioner and 20.7% consulted a psychiatrist. CONCLUSIONS: The prevalence of
      lifetime suicide-related behaviour in Beijing is lower than in Western countries,
      but the low percentage of subjects treated for suicide-related behaviour
      indicates a major public health problem that should be addressed. National
      surveys are needed to further explore the prevalence of suicide-related behaviour
      in China.

PMID- 19153925
TI  - Adult attachment styles in panic disorder with and without comorbid adult
      separation anxiety disorder.
AB  - OBJECTIVE: Attachment theory suggests that anxious attachment styles are
      associated with risk to psychiatric disorder, especially anxiety disorders.
      Separation anxiety would appear to be a core form of anxiety that is associated
      with anxious attachment. Nevertheless, as yet no research has examined the
      relationship of attachment styles to adult separation anxiety disorder, a
      condition that has only recently been fully recognized. METHOD: The Attachment
      Style Questionnaire was used to examine attachment styles among 83 consecutive
      anxiety clinic patients diagnosed with panic disorder with agoraphobia and those
      re-assigned from that category to adult separation anxiety disorder. RESULTS:
      Dimensional associations showed strong correlations with scales measuring anxious
      attachment and separation anxiety. Patients assigned to the separation anxiety
      group scored significantly higher than those in the panic disorder group on the
      scales of Need for Approval and Preoccupation with Relationships. CONCLUSIONS:
      The findings finally dispel the notion that separation anxiety and anxious
      attachment are relevant to panic disorder with agoraphobia, suggesting instead
      that that constellation is confined to a separate group, namely that of adult
      separation anxiety disorder. Possible implications for treatment are considered.

PMID- 19153926
TI  - Can the highly cited psychiatric paper be predicted early?
AB  - OBJECTIVE: Predicting the impact of any research article on its scientific
      discipline is often viewed as requiring the passage of time. A recent BMJ
      article, however, reported that an article's citation rate at 2 years could be
      predicted by data available 3 weeks following publication. The question remains
      as to whether establishing a citation trajectory at an early stage holds for
      psychiatric publications, given the low percentage of psychiatric articles in
      their analysis. The aim of the current article was to critically examine this
      area of the scientific literature. METHOD: Data were collected from the Institute
      for Scientific Information on scientific papers published in January/February
      2006, in the top 30 psychiatric journals. Analyses examined the comparative
      impact of early citation numbers and several predictors identified in the BMJ
      article. RESULTS: Only two BMJ variables (a larger number of references per
      article and larger number of authors) predicted higher citations at 2 years in
      the principal analysis. Citation counts at 1, 3, 6 and 12 months predicted
      citations at 2 years, with increasing success over time, and such citation counts
      were distinctly superior to the quantified variables in the previous study.
      CONCLUSIONS: It appears doubtful that data available at 3 weeks after publication
      for psychiatric articles are useful in predicting citation counts at 2 years. The
      trajectory of citation counts for a psychiatric article becomes more apparent
      with time.

PMID- 19153927
TI  - Risperidone and pituitary adenomas.

PMID- 19153928
TI  - China engages global health governance: processes and dilemmas.
AB  - Using HIV/AIDS, Severe Acute Respiratory Syndrome (SARS), and avian influenza as
      case studies, this paper discusses the processes and dilemmas of China's
      participation in health governance, both at the domestic level and the global
      level. Globalization has eroded the boundary between public and private health
      and between domestic and global health governance. In addition, the SARS outbreak
      of 2002-2003 focused global attention on China's public health. As a rising power
      with the largest population on earth, China is expected by the international
      community to play a better and more active role in health management. Since the
      turn of this century, China has increasingly embraced multilateralism in health
      governance. This paper argues that China's multilateral cooperation is driven by
      both necessity and conscious design. International concerns about good governance
      and its aspiration to become a 'responsible' state have exerted a normative
      effect on China to change tack. Its interactions with United Nations agencies
      have triggered a learning process for China to securitize the spread of
      infectious diseases as a security threat. Conversely, China has utilized
      multilateralism to gain access to international resources and technical
      assistance. It is still a matter of debate whether China's cooperative engagement
      with global health governance can endure, because of the persistent problems of
      withholding information on disease outbreaks and because of its insistence on the
      Westphalian notion of sovereignty.

PMID- 19153929
TI  - Time for an ecosystem approach to public health? Lessons from two infectious
      disease outbreaks in Canada.
AB  - Ecosystem approaches recognize the complexity of many contemporary public health
      challenges and offer an alternative for dealing with problems that have proven
      intractable and unresponsive to conventional public health strategies. Infectious
      disease outbreaks are among the most dramatic aspects of systems failure, and the
      Canadian cases of SARS (Severe Acute Respiratory Syndrome) in Toronto, and the E.
      coli outbreak in Walkerton, serve as useful illustrative examples. This paper
      examines some of the limitations of current public health approaches, the
      fundamental tenets of an alternative, transdisciplinary ecosystem approach, and
      changes necessary for implementation, including those in philosophical approach,
      communications and education, and, finally, institutions and governance.

PMID- 19153930
TI  - The stages of international (global) health: histories of success or successes of
      history?
AB  - International health funders, leaders and researchers frequently cite 'successes'
      in this field as validation for past labours and justification for future
      endeavours. However, the question of what constitutes success - from both
      historical and contemporary perspectives - has been inadequately analysed. This
      paper reviews and periodises understandings of success in international/global
      health during the past century and a half, mapping out shifts and continuities
      over time. It then turns to the implications of these changing conceptualizations
      for current and future global health ideologies, strategies and activities. It
      concludes by arguing that historians of global health and policymakers need to
      interact further so that historians are exposed to the contemporary problems of
      global health and policymakers better understand the historical complexity of
      extracting 'lessons' from the past.

PMID- 19153931
TI  - Coping and health behaviours in times of global health crises: lessons from SARS
      and West Nile.
AB  - We examined perceived threats of Severe Acute Respiratory Syndrome and West Nile
      Virus using an Internet-based questionnaire. Higher levels of perceived threats
      of diseases were associated with increases in a variety of ways of coping,
      including empathic responding and wishful thinking. In turn, we examined how
      coping with the perceived health threat was related to two specific health
      related behaviours: taking recommended precautions, and avoiding people in an
      attempt to avoid disease. The findings from linear regression indicated that
      empathic responding, in response to the threat of a virulent agent, was related
      to taking recommended and effective health precautions. On the other hand,
      wishful thinking was associated with those behaviours that may potentially lead
      to economic hardship in afflicted areas, such as avoiding people perceived to be
      at risk for an infectious agent. Implications for health promotion are discussed.

PMID- 19153932
TI  - Effectiveness of research training workshop taught by traditional and video
      teleconference methods in a developing country.
AB  - The developing countries are currently facing a double burden of communicable and
      non-communicable diseases. Physician-scientists, trained in patient care and
      research skills are crucial in performing cutting-edge clinical research in the
      developing countries. A major unmet challenge has been the lack of local
      expertise and the increasing problem of 'brain drain'. The current study was an
      effort to present and assess a model of research training to health-care
      professionals in Pakistan in order to increase the research skills. The objective
      of the current study was to assess the effectiveness of two different methods of
      research training. An epidemiologic research training workshop was offered to
      health-care professionals in Pakistan by face-to-face (F2F) and video
      teleconferencing (VTC) methods. A total of 38 F2F and 18 VTC participants were
      included in the workshop which was conducted by research faculty from the
      University of Pittsburgh. To assess knowledge, pre- and post-test were done.
      Within each group, paired sample T-test showed significant improvement in scores
      after the completion of workshop (p<0.001 for F2F and VTC). In the F2F group,
      mean scores increased from 11.13 (pre-test) to 15.08 (post-test) and in the VTC
      group, scores increased from 10.67 (pre-test) to 13.22 (post-test). Two sample T
      test was found statistically significant (p<0.001). We present a model for
      training physicians in public health by providing in-house research skills
      training which can be used to strengthen the local capacity and reduce increasing
      problems of brain drain.

PMID- 19153933
TI  - Utilization of respondent-driven sampling among a population of child workers in
      the diamond-mining sector of Sierra Leone.
AB  - This article describes the implementation of respondent driven sampling (RDS) in
      a study conducted in Kono District, Sierra Leone. RDS was used to identify
      children, under the age of 18 years old, working in the diamond sector of Sierra
      Leone. This includes children working directly as diamond miners as well as
      children working in the informal sector connected to the diamond field. The
      article seeks to postulate that RDS is a suitable method for a rapid approach to
      a population that is unidentified in size and demonstrate how RDS can reach a
      study population within a limited period.

PMID- 19153936
TI  - Cardiovascular disease risk factors in a population-based sample of Norwegian
      children and adolescents.
AB  - OBJECTIVE: The objective of the study was to describe the distribution of
      cardiovascular disease (CVD) risk factors, and to evaluate the extent of
      clustering of CVD risk factors in Norwegian children and adolescents. MATERIAL
      AND METHODS: A randomly selected cohort of 9-year-olds and 15-year-olds from all
      regions of the country was sampled. Of 2,818 subjects invited to participate,
      2,299 accepted, giving an overall participation rate of 82%. RESULTS: Mean (SD)
      values for the main risk factors for 9-year-old and 15-year-old girls and boys
      were: total cholesterol (TC) (mmol/L) 4.49 (0.73), 4.37 (0.68), 4.19 (0.76) and
      3.80 (0.69), respectively; triglycerides (TG) (mmol/L) 0.72 (0.33), 0.63 (0.32),
      0.79 (0.32) and 0.82 (0.47), respectively; high density lipoprotein cholesterol
      (HDL-c) (mmol/L) 1.70 (0.35), 1.79 (0.40), 1.61 (0.34) and 1.42 (0.30),
      respectively; systolic blood pressure (mmHg) 102.6 (7.7), 103.3 (7.7), 109.0
      (8.8) and 115.3 (9.0), respectively; and homeostasis model assessment score
      (HOMA) 1.29 (0.83), 1.19 (0.78), 2.10 (1.37) and 2.14 (1.49), respectively. At
      least five risk factors were found in 11.1 (95% confidence interval (CI) 8.76 to
      13.44) times as many participants as expected. A significant degree of clustering
      of CVD risk factors was found in 11.4% (95% CI, 9.8 to 13.0) of the study
      population, and these had mean Z scores of 1.24 (0.06) and 1.04 (0.08) for the 9
      year-olds and 15-year-olds, respectively. CONCLUSION: This study presents
      national reference data on selected CVD risk factors in children and adolescents.

PMID- 19153937
TI  - [Long-acting bronchodilators (formoterol and salmeterol) for treatment of
      asthma].

PMID- 19153938
TI  - [Nikolaus Konietzko on the occasion of his 70th Birthday].

PMID- 19153939
TI  - A randomized, open-label trial comparing methadone and Levo-Alpha-Acetylmethadol
      (LAAM) in maintenance treatment of opioid addiction.
AB  - INTRODUCTION: Levo-Alpha-Acetylmethadol (LAAM) is a synthetic opioid analgesic
      with mu-agonistic activity and a long duration of action. There are several,
      almost exclusively US American studies showing the efficacy of LAAM as a
      maintenance drug which has the advantage that it needs to be administered only
      three times a week. LAAM is currently not marketed in EU countries due to cardiac
      complications. We report on the first European multi-center, parallel group,
      flexible dose, open-label, randomized clinical trial comparing LAAM and methadone
      in patients with opioid dependence. METHODS: Eighty-four opioid addicts in
      ongoing maintenance treatment with stable methadone doses were treated with
      methadone under study conditions for 5 weeks (run-in phase), then randomly
      assigned to a methadone (n=41) or a LAAM (n=43) group. Study duration was 24
      weeks after randomization. Objective measures (drug urine screenings, retention
      rate), subjective measures (symptoms of withdrawal and craving, report of
      substance use), and safety data were collected weekly. The main outcome criterion
      was the number of opiate-free urine samples per number of weeks of study
      participation. RESULTS: Non-inferiority was shown for LAAM compared to methadone.
      Both substances were well tolerated. There were no clinical cardiac complications
      in either group. DISCUSSION: Our study confirmed the results of previous
      investigations with LAAM as being efficacious and well tolerated in opioid
      dependence. A discussion to reconsider the availability of LAAM is recommended.

PMID- 19153940
TI  - The effects of donepezil on postlearning sleep EEG of healthy older adults.
AB  - INTRODUCTION: Aging is associated with cholinergic hypofunction and memory
      decline. Cholinergic activity also plays a crucial role in sleep-dependent memory
      consolidation. The acetylcholinesterase inhibitor (AChE-I) donepezil has been
      found to increase sleep-related procedural memory consolidation in healthy older
      adults in a previous study. METHODS: Data of the former study were reanalyzed
      with regard to the effects of donepezil on the sleep EEG of healthy older adults.
      This analysis was conducted with a special focus on spectral parameters of sleep,
      which have previously been linked to plasticity-related processes during sleep,
      i.e., sigma and delta activity. Forty-two participants (aged: 60-77 years)
      received 5 mg of the AChE-I donepezil orally 30 min before bedtime in a placebo
      controlled, double-blind design. Power values for EEG delta, theta, alpha1, alpha
      2, sigma, beta and gamma frequency bands were calculated for stage 2 NREM sleep,
      SWS and REM sleep. RESULTS: In line with our hypotheses, the AChE-I donepezil led
      to an increase in sigma activity during stage 2 NREM sleep and delta activity
      during slow wave sleep. CONCLUSION: These results suggest that an AChE-I
      facilitates processes of sleep-dependent memory consolidation in older adults.

PMID- 19153941
TI  - Rosiglitazone in the assistance of metabolic control during olanzapine
      administration in schizophrenia: a pilot double-blind, placebo-controlled, 12
      week trial.
AB  - INTRODUCTION: Excessive body weight gain (BWG), hyperglycemia and dyslipidemia
      are important side effects of olanzapine. We assessed the effects of
      rosiglitazone on BWG, the insulin resistance index (HOMA-IR), lipids, glycated
      hemoglobin and fibrinogen in olanzapine-treated schizophrenia patients. METHODS:
      Thirty patients taking olanzapine (10-20 mg daily for 8 months) were randomly
      allocated to rosiglitazone (n=15; 4 to 8 mg daily) or placebo (n=15) in a 12-week
      double-blind protocol. Anthropometric and biochemical variables were evaluated at
      baseline, weeks 6 and 12. RESULTS: The rosiglitazone and placebo groups gained
      3.2+/-4.5 and 2.2+/-2.3 kg, respectively (p=0.65). Insulin and the HOMA-IR
      significantly decreased after rosiglitazone (p<0.05). Rosiglitazone did not
      improve the lipid profile, fibrinogen and Hb1c levels. DISCUSSION: The positive
      impact of rosiglitazone was limited to improved glycemic control. It cannot be
      recommended for metabolic control during olanzapine treatment.

PMID- 19153942
TI  - Dopamine D1 receptor gene polymorphism is associated with prophylactic lithium
      response in bipolar disorder.
AB  - BACKGROUND: Previously, we have found an association between the -48 A/G
      polymorphism of the dopamine receptor D1 (DRD1) gene and bipolar disorder. The
      aim of the present study was to investigate a possible association of this
      polymorphism with the quality of the prophylactic lithium response in bipolar
      patients. METHODS: Ninety-two patients (39 male, 53 female), aged 30-77 (mean: 54
      years) were studied. They have received lithium for prophylactic purposes for 5
      27 years (mean: 15 years). Twenty-four patients were identified as excellent
      lithium responders (ER), 48 patients as partial responders (PR), and 20 patients
      were non-responders (NR). They all were genotyped for -48 A/G polymorphism of the
      DRD1 gene. RESULTS: The frequency of G/G genotype in ER, PR, and NR patients was
      21%, 48%, and 60%, respectively, and the frequency of G allele was 58%, 76%, and
      80%, respectively. DISCUSSION: The results obtained suggest that the higher
      frequency of G allele, and G/G genotype, which has been associated with a
      predisposition to bipolar illness, is also connected with a poorer prophylactic
      effect of lithium.

PMID- 19153943
TI  - Insulin-like growth factor-I (IGF-I) serum concentrations in depressed patients:
      relationship to saliva cortisol and changes during antidepressant treatment.
AB  - INTRODUCTION: The present study was designed to test the hypothesis that total
      and free insulin-like growth factor-I (IGF-I) serum concentrations in depressed
      patients are related to hypothalamus-pituitary-adrenal (HPA) system activity and
      show a longitudinal decline in patients responding to treatment as well as to
      declining HPA system activity. METHODS: We measured total and free IGF-I as well
      as IGF-binding protein-3 in 77 depressed patients after wash-out of pre
      medication and again after 28 or 35 days of treatment with paroxetine or
      amitriptyline. RESULTS: Total but not free IGF-I serum concentrations are related
      to saliva cortisol concentrations in drug-free depressed patients. In responders
      to both amitriptyline and paroxetine, total IGF-I serum concentrations declined
      during treatment. DISCUSSION: Our findings show IGF-I to be related to HPA system
      activity and to decline in responders to treatment while serum concentrations of
      the biologically active free IGF-I are neither related to HPA system activity nor
      do they change during the course of treatment. Our data do not support the
      hypothesis that free IGF-I may play a major role in physical disturbances in
      depressed patients.

PMID- 19153945
TI  - Excessive talking triggered by methylphenidate in a boy with ADHD.

PMID- 19153944
TI  - Effects of six second generation antipsychotics on body weight and metabolism -
      risk assessment and results from a prospective study.
AB  - BACKGROUND: Due to the association of second generation antipsychotics (SGAs)
      with weight gain and alterations of glucose and lipid homeostasis, we aimed to
      group six commonly prescribed SGAs into classes of differing risks. METHODS:
      Twenty-eight patients meeting the criteria for a diagnosis of schizophrenic
      disorder according to ICD-10 were assigned to monotherapy with olanzapine,
      clozapine, quetiapine, amisulpride, ziprasidone or risperidone. The levels of
      glucose and lipid metabolism were assessed before and after 28 days of treatment.
      RESULTS: Based on cluster analysis, olanzapine and clozapine were found to
      constitute a high-risk group for metabolic dysregulation while amisulpride,
      quetiapine, risperidone and ziprasidone could be assigned to a non-high-risk
      group. Subjects from the high-risk group displayed significant weight gain with
      concomitant increases of HOMA-IR, levels of insulin, total cholesterol, TG, LDL-C
      and leptin. No significant changes were observed in the non-high-risk group.
      CONCLUSION: The results of this study support the conclusion of the Consensus
      Development Conference on Antipsychotic Drugs and Obesity and Diabetes that
      certain SGAs are associated with a higher risk for weight gain, insulin
      resistance and dyslipidemia.

PMID- 19153946
TI  - Use of thiamine in the treatment of post-electroconvulsive therapy delirium.

PMID- 19153947
TI  - Improvement of obsessive-compulsive disorder with divalproex and lamotrigine in
      two patients with bipolar II disorder.

PMID- 19153950
TI  - [Quantification of videostroboscopic vocal cord findings].

PMID- 19153952
TI  - [Anxiety and panic disorders].

PMID- 19153953
TI  - [CME ultrasonography 26. Check up and what now?].

PMID- 19153954
TI  - [The way people would like their lives to end].
AB  - By means of four dying trajectories we carried out a survey with people working
      in nursing institutions and participants of workshops preparing for retirement
      about the way they would like to spend the final phase of their lives (n = 159).
      The average lifetime women desired was 85,6 years, that of men 83,8 years. 43%
      wished for a sudden death to avoid suffering. 50% preferred to die within a
      couple of weeks or months to have time to say goodbye. In order to avoid
      dependence on others and the need for care 34% would forfeit at least six years,
      61% at least two years of their lives. 14% would not trade off any time at all.

PMID- 19153955
TI  - [Treatment of Crohn's disease].
AB  - The therapy of Crohn's disease depends on its disease activity. For those
      different disease activities (such as flare, chronic active disease, remission)
      varying treatment concepts are followed. This overview presents important
      concepts in the treatment of Crohn's disease.

PMID- 19153956
TI  - [Thyroid nodules: clinical management and differential diagnosis].
AB  - Thyroid nodules are common and are frequently benign. The prevalence of thyroid
      nodules ranges from 3-7% (palpation) to 50% (ultrasonography). Thyroid cancer
      occurs in 5-10% of nodules. Thyroid ultrasonography (US) is not a screening test
      but all patients with palpable thyroid nodule should undergo US examination. US
      guided fine-needle aspiration citology (FNC) is recommendend for nodules with
      suspicious features at US examination or when clinical risk factors occur. A
      radioisotope scan is useful if the TSH is low or suppressed to detect (benign)
      functioning nodules.

PMID- 19153957
TI  - [Elevated blood glucose concentration].

PMID- 19153965
TI  - An example for an underpowered study: a comment on Ginkgo biloba for mild to
      moderate dementia in a community setting by McCarney et al.

PMID- 19153966
TI  - A comment on Ginkgo biloba for mild to moderate dementia in a community setting
      by McCarney et al.

PMID- 19153967
TI  - A comment on Ginkgo biloba for mild to moderate dementia in a community setting
      by McCarney et al.

PMID- 19153969
TI  - Sample size requirements to detect an intervention by time interaction in
      longitudinal cluster randomized clinical trials.
AB  - In designing a longitudinal cluster randomized clinical trial (cluster-RCT), the
      interventions are randomly assigned to clusters such as clinics. Subjects within
      the same clinic will receive the identical intervention. Each will be assessed
      repeatedly over the course of the study. A mixed-effects linear regression model
      can be applied in a cluster-RCT with three-level data to test the hypothesis that
      the intervention groups differ in the course of outcome over time. Using a test
      statistic based on maximum likelihood estimates, we derived closed-form formulae
      for statistical power to detect the intervention by time interaction and the
      sample size requirements for each level. Importantly, the sample size does not
      depend on correlations among second-level data units and the statistical power
      function depends on the number of second- and third-level data units through
      their product. A simulation study confirmed that theoretical power estimates
      based on the derived formulae are nearly identical to empirical estimates.

PMID- 19153970
TI  - Doubly robust generalized estimating equations for longitudinal data.
AB  - A popular method for analysing repeated-measures data is generalized estimating
      equations (GEE). When response data are missing at random (MAR), two
      modifications of GEE use inverse-probability weighting and imputation. The
      weighted GEE (WGEE) method involves weighting observations by their inverse
      probability of being observed, according to some assumed missingness model.
      Imputation methods involve filling in missing observations with values predicted
      by an assumed imputation model. WGEE are consistent when the data are MAR and the
      dropout model is correctly specified. Imputation methods are consistent when the
      data are MAR and the imputation model is correctly specified.Recently, doubly
      robust (DR) methods have been developed. These involve both a model for
      probability of missingness and an imputation model for the expectation of each
      missing observation, and are consistent when either is correct. We describe DR
      GEE, and illustrate their use on simulated data. We also analyse the INITIO
      randomized clinical trial of HIV therapy allowing for MAR dropout.

PMID- 19153971
TI  - Vaginal robot-assisted radical hysterectomy (VRARH) after laparoscopic staging:
      feasibility and operative results.
AB  - BACKGROUND: To describe a technique of vaginal robot-assisted radical
      hysterectomy (VRARH) that utilizes the advantages of a robotic system and
      eliminates the manipulation of cancer tissue. METHODS: A prospective study was
      performed for VRARH using the da Vinci robotic surgical system in 12 patients.
      The procedure was indicated in patients with cervical cancer stage FIGO IB1 after
      laparoscopic lymphadenectomy. A tumour-adapted vaginal cuff was created
      transvaginally. RESULTS: All operations were completed with minimal blood loss
      (mean 123 ml). The mean operative time including para-aortic lympadenectomy was
      356 min, the vaginal cuff creation took 43 min and the radical robotic resection
      68 min. No uterine manipulator was used. There were no bladder or bowel
      complications and no conversion to standard laparoscopy or laparotomy.
      CONCLUSIONS: The VRARH technique combines the advantages of the vaginal route and
      robotic laparoscopic surgery: tumour contamination is avoided and complications
      are minimized. This procedure could be superior to techniques described
      previously.

PMID- 19153972
TI  - Use of internally nuclease-protected single-strand DNA oligonucleotides and
      silencing of the mismatch repair protein, MSH2, enhances the replication of
      corrected cells following gene editing.
AB  - BACKGROUND: Gene editing is potentially a powerful technology for introducing
      genetic changes by using short single-stranded DNA oligonucleotides (ssODNs).
      However, their efficiency is reduced by the mismatch repair system, especially
      MSH2, which may suppress gene editing, although findings vary depending on
      readout and type of oligonucleotide used. Additionally, successfully edited cells
      are reported to arrest at the S- or G2-phase. In the present study, we evaluate
      whether a novel ssODN design and down-regulation of MSH2 expression allows the
      isolation of replicating gene-edited cells. METHODS: Cultured Chinese hamster
      ovary cells expressing mutated enhanced green fluorescent protein were targeted
      with ssODNs of varying design, all capable of restoring fluorescence, which
      allows the monitoring of correction events by flow cytometry. Converted cells
      were isolated by cell sorting and grown to determine colony formation
      efficiencies. MSH2 expression was suppressed with small interfering RNA and the
      cell cycle distribution of cells transfected with ssODN was quantified by flow
      cytometry, following propidium iodide or DRAQ5 staining. RESULTS: Although
      efficiency was higher using ssODN end-protected with phosphorothioate, the
      potential of edited cells to form colonies was lower than those targeted with
      unmodified ssODN. We established that ssODN transfection itself perturbs the cell
      cycle and that MSH2 gene silencing increases correction efficiency. In both
      cases, however, the effect was dependent on the positioning of the protected
      nucleotides. Importantly, when internally protected ssODN was used in combination
      with MSH2 suppression, a higher proportion of G1-phase corrected cells was
      observed 48-64 h after transfection. CONCLUSIONS: Use of internally protected
      ssODN and downregulating cellular MSH2 activity may facilitate isolation of
      viable, actively replicating gene-edited cells.

PMID- 19153973
TI  - Tetrapterosides A and B, two new oleanane-type saponins from Tetrapleura
      tetraptera.
AB  - From the stem bark of Tetrapleura tetraptera, two new oleanane-type saponins,
      tetrapteroside A 3-O-{6-O-[(2E,6S)-2,6-dimethyl-6-hydroxyocta-2,7-dienoyl]-beta-D
      glucopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 3)-beta-D-glucopyranosyl-(1
      --> 4)-[beta-D-glucopyranosyl-(1 --> 2)]-beta-D-glucopyranosyl}-3,27
      dihydroxyoleanolic acid (1), and tetrapteroside B 3-O-{ beta-D-glucopyranosyl-(1 
      -> 2)-6-O-[(E)-feruloyl]-beta-D-glucopyranosyl-(1 --> 3)-beta-D-glucopyranosyl-(1
      --> 4)-[beta-D-glucopyranosyl-(1 --> 2)]-beta-D-glucopyranosyl}-3,27
      dihydroxyoleanolic acid (2), were isolated. Further extractions from the roots
      led to the isolation of four known oleanane-type saponins. Their structures were
      elucidated by the combination of mass spectrometry (MS), one and two-dimensional
      NMR experiments.

PMID- 19153974
TI  - Pseudo-bridging silanols as versatile Bronsted acid sites of amorphous
      aluminosilicate surfaces.
AB  - Amorphization tunes acidity: Pseudo-bridging silanols, suggested as versatile
      Bronsted acid groups by molecular modeling studies, are obtained by shifted
      hydrolysis of Si-O-Al bridges formed by the thermal treatment of silica deposited
      on gamma-Al(2)O(3) (100), and appear under given pretreatment conditions.
      Demixing of part of the silica from the aluminosilicate phase is predicted upon
      excess water adsorption.

PMID- 19153975
TI  - Ruthenium-catalyzed synthesis of functionalized dienes from propargylic esters:
      formal cross-coupling of two carbenes.
AB  - Cross-coupling carbenes: The coupling of a propargylic ester with a diazoalkane
      in the presence of [RuCl(cod)Cp*] catalyst leads to the formation of
      functionalized conjugated dienes with high stereoselectivity. The reaction
      involves the cross-coupling of a vinylcarbene fragment, arising from a ruthenium
      catalyzed propargylic ester rearrangement, with a diazoalkane carbene.

PMID- 19153976
TI  - Potassium tert-butoxide-catalyzed dehydrogenative Si-O coupling: reactivity
      pattern and mechanism of an underappreciated alcohol protection.
AB  - A remarkable tert-butoxide-catalyzed coupling of alcohols and silanes is
      reported. Dihydrogen and not hydrochloric acid (generated in the prevalent,
      related coupling of alcohols and chlorosilanes) is formed as the sole by-product.
      A comprehensive survey of common silanes provides a reliable tool for the
      predictability of their reactivity under defined reaction conditions. The debated
      mechanism of this transformation is investigated monitoring the stereochemical
      course at the silicon atom by means of a silicon-stereogenic silane. On this
      basis, a transition state for the enantiospecific Si-O coupling step is suggested
      rationalizing the observed frontside attack and thus retention at the silicon
      atom.

PMID- 19153977
TI  - RNA interference: from basic research to therapeutic applications.
AB  - An efficient mechanism for the sequence-specific inhibition of gene expression is
      RNA interference. In this process, double-stranded RNA molecules induce cleavage
      of a selected target RNA (see picture). This technique has in recent years
      developed into a standard method of molecular biology. Successful applications in
      animal models have already led to the initiation of RNAi-based clinical trials as
      a new therapeutic option.Only ten years ago Andrew Fire and Craig Mello were able
      to show that double-stranded RNA molecules could inhibit the expression of
      homologous genes in eukaryotes. This process, termed RNA interference, has
      developed into a standard method of molecular biology. This Review provides an
      overview of the molecular processes involved, with a particular focus on the
      posttranscriptional inhibition of gene expression in mammalian cells, the
      possible applications in research, and the results of the first clinical studies.

PMID- 19153978
TI  - Soman poisoning alters p38 MAPK pathway in rat cerebellar Purkinje cells.
AB  - The aim of the study was to evaluate the expression of phosphorylated p38 mitogen
      activated protein kinase (p38 MAPK) and MAPK-activated transcription factors elk
      1, c-jun and c-myc in rat cerebellar Purkinje cells after soman poisoning to
      investigate the pathogenetic mechanism of non-specific long-term adverse effects
      of nerve agents. Male Wistar rats were poisoned by intramuscular administration
      of soman at a dose 60 microg kg(-1) (80% LD(50)), while control animals were
      administered physiological saline. Samples were taken 1, 7 and 14 days after
      poisoning, immunohistochemically stained and p-p38MAPK, p-c-jun, p-c-myc, and p
      elk-1 expressions were measured using computer image analysis. An increased
      expression of phosphorylated p38 MAPK and c-myc 14 days after soman poisoning was
      found, while both activated elk-1 and c-jun expression remained unchanged 1, 7
      and 14 days after intoxication. Late activation of p38 MAPK and their targets
      might be the underlying mechanism of chronic neurophysiological adverse effects.

PMID- 19153979
TI  - Selective blockade of mGlu5 metabotropic glutamate receptors is hepatoprotective
      against fulminant hepatic failure induced by lipopolysaccharide and D
      galactosamine in mice.
AB  - This study was designed to investigate the influence of 2-methyl-6-phenylethynyl
      pyridine hydrochloride (MPEP), an antagonist of metabotropic glutamate receptor
      subtype 5, in lipopolysaccharide (LPS) and d-galactosamine (D-GalN)-induced
      fulminant hepatic failure in mice. Mice were given an intraperitoneal injection
      of 50 microg kg(-1) LPS and 500 mg kg(-1) D-GalN. MPEP (1, 5 and 25 mg kg(-1))
      was administered intraperitoneally 1 h before LPS/D-GalN injection. Twenty-four
      hours after administration of LPS/D-GalN, plasma was collected and used for
      biochemical assays. Mice were euthanized and histological analysis and
      toxicological parameters were carried out in the liver. MPEP, at all doses
      tested, protected against the increase in aspartate and alanine aminotransferase
      activities induced by LPS/D-GalN exposure. Ascorbic acid levels were not altered
      in all experimental groups. Glutathione S-transferase activity was increased by
      administration of LPS/D-GalN and MPEP did not modify the enzyme activity in mice.
      MPEP, at the doses of 5 and 25 mg kg(-1), was effective in protecting against the
      decrease in catalase activity caused by LPS/D-GalN administration in mice. The
      histological data showed that sections of liver from LPS/D-GalN-exposed mice
      presented extensive injuries. MPEP, at all doses tested, reduced the scores of
      liver damage and markedly ameliorated the degree of liver damage. The
      hepatoprotective effect of MPEP on fulminant hepatic failure induced by LPS and D
      GalN in mice was demonstrated.

PMID- 19153980
TI  - Permethrin induces lymphocyte DNA lesions at both Endo III and Fpg sites and
      changes in monocyte respiratory burst in rats.
AB  - Pyrethroids are widely used insecticides of low acute toxicity in mammals but the
      consequences of long-term exposure are of concern. Their insecticidal action is
      related to neurotoxicity and, in addition, there are indications of mammalian
      immuno-toxicity. In this work the effect of 60 days permethrin (150 mg kg(-1)
      body weight/day) exposure on two types of leukocytes (monocytes and lymphocytes)
      in adolescent rats was investigated. In particular, the monocyte respiratory
      burst response was first investigated, followed by studies on the degree and type
      of lymphocyte DNA damage induced by permethrin at this stage of life. Permethrin
      treatment reduces the monocyte respiratory burst response to phorbol myristate
      acetate, thereby decreasing superoxide anion (65%) and hydrogen peroxide (37%)
      production. Moreover an increase [correction made here after initial online
      publication] in monocyte plasma membrane fluidity in the hydrophilic-hydrophobic
      interface of the lipid bilayer was measured. Data obtained from the comet assay
      show that permethrin induces lymphocyte DNA lesions at both formamido pyrimidine
      glycosylase (Fpg) and endonuclease III (Endo III) sites in adolescent rats. Our
      results indicate the key role of permethrin in oxidative stress whose
      consequences lead to biochemical and functional changes. The reduced phagocyte
      respiratory burst induced by permethrin treatment and the type of DNA damage
      measured could represent new relevant aspects of pyrethroid toxicity which should
      be considered for human health.

PMID- 19153981
TI  - Elucidation of the complexation mechanism between (+)-usnic acid and
      cyclodextrins studied by isothermal titration calorimetry and phase-solubility
      diagram experiments.
AB  - In the present work the complexation mechanism between (+)-usnic acid (UA) and
      cyclodextrins (CDs) has been investigated by isothermal titration calorimetry
      (ITC) and phase-solubility diagrams using pH as a tool for modifying the molecule
      ionization. ITC experiments have been employed to evaluate the stoichiometry of
      interaction (N), affinity constants (K), and thermodynamic parameter variation
      associated with complexation between (+)-UA and alpha-, beta-, HP-beta-, SBE-beta
      , and gamma-CD. It was shown that (+)-UA did not interact with alpha-CD and
      tended to interact more favorably with gamma-CD (K = 1030 M(-1), DeltaG = -17.18
      kJ x mol(-1)) than beta-CD (K = 153 M(-1), DeltaG = -12.46 kJ x mol(-1)) forming
      1:1 complexes. It was also demonstrated using ITC and solubilization experiments
      that chemical modifications of the parent beta-CD resulted in stronger and more
      spontaneous interactions (K = 281 M(-1), DeltaG = -13.97 kJ x mol(-1) for SBE
      beta-CD and K = 405 M(-1), DeltaG = -14.87 kJ x mol(-1) for HP-beta-CD). Analysis
      of the thermodynamic data suggested that van der Waals forces and hydrogen bonds
      were responsible for the formation of complexes with a predominance of van der
      Waals forces. Finally, pH induced modifications of (+)-UA ionization provided
      important informations relative to the topology of the interaction between (+)-UA
      molecule and the gamma-CD cavity, which were confirmed by molecular modeling.

PMID- 19153982
TI  - Visions: the art of science.

PMID- 19153985
TI  - Effect of Citrus paradisi extract and juice on arterial pressure both in vitro
      and in vivo.
AB  - Citrus paradisi (grapefruit) consumption is considered as beneficial and it is
      popularly used for the treatment of a vast array of diseases, including
      hypertension. In the present study, the coronary vasodilator and hypotensive
      effects of Citrus paradisi peel extract were assessed in the Langendorff isolated
      and perfused heart model and in the heart and lung dog preparation. In both
      models, Citrus paradisi peel extract decreased coronary vascular resistance and
      mean arterial pressure when compared with control values (60 +/- 15 x 10(7) dyn s
      cm(-5) vs 100 +/- 10 x 10(7) dyn s cm(-5) and 90 mmHg vs 130 +/- 15 mmHg,
      respectively). These decreases in coronary vascular resistance and mean arterial
      pressure were blocked when isolated and perfused hearts and mongrel dogs were pre
      treated with L-NAME. In humans, Citrus paradisi juice decreased diastolic
      arterial pressure and systolic arterial pressure both in normotensive and
      hypertensive subjects. Citrus paradisi juice produced a greater decrease in mean
      arterial pressure when compared with Citrus sinensis juice, cow milk and a
      vitamin C-supplemented beverage. However, more detailed studies are required to
      isolate, purify and evaluate the chemical compounds responsible for this
      pharmacological effect and to clarify its possible role for treating
      hypertension.

PMID- 19153991
TI  - Core/Shell semiconductor nanocrystals.
AB  - Colloidal core/shell nanocrystals contain at least two semiconductor materials in
      an onionlike structure. The possibility to tune the basic optical properties of
      the core nanocrystals, for example, their fluorescence wavelength, quantum yield,
      and lifetime, by growing an epitaxial-type shell of another semiconductor has
      fueled significant progress on the chemical synthesis of these systems. In such
      core/shell nanocrystals, the shell provides a physical barrier between the
      optically active core and the surrounding medium, thus making the nanocrystals
      less sensitive to environmental changes, surface chemistry, and photo-oxidation.
      The shell further provides an efficient passivation of the surface trap states,
      giving rise to a strongly enhanced fluorescence quantum yield. This effect is a
      fundamental prerequisite for the use of nanocrystals in applications such as
      biological labeling and light-emitting devices, which rely on their emission
      properties. Focusing on recent advances, this Review discusses the fundamental
      properties and synthesis methods of core/shell and core/multiple shell structures
      of II-VI, IV-VI, and III-V semiconductors.

PMID- 19153992
TI  - Citrate transport and metabolism in mammalian cells: prostate epithelial cells
      and prostate cancer.
AB  - Citrate, an organic trivalent anion, is a major substrate for generation of
      energy in most cells. It is produced in mitochondria and used either in the
      Krebs' cycle or released into cytoplasm through a specific mitochondrial
      carriers. Citrate can also be taken up from blood through different plasma
      membrane transporters. In the cytoplasm, citrate can be used ultimately for fatty
      acid synthesis, which is increased in cancer cells. Here, we review the ways in
      which citrate can be transported and discuss the changes in transport and
      metabolism that occur in cancer cells. The primary focus is on the prostate
      gland, which is known to produce and release large amounts of citrate during its
      normal secretory function. The significant changes that occur in citrate-related
      metabolism and transport in prostate cancer are the second focus. This review
      strives to relate these mechanisms to molecular biology on the one hand and to
      clinical applications on the other.

PMID- 19153993
TI  - The need for the incorporation of phylogeny in the measurement of biological
      diversity, with special reference to ecosystem functioning research.
AB  - Defining and measuring biodiversity is an important research area in biology,
      with very interesting theoretical and applied aspects. Numerous definitions have
      been proposed, and these definitions of biodiversity influence how it is
      measured. From the still commonly used measure of species diversity, through
      higher taxon diversity, molecular measures, ecological measures and indicator
      taxa, these measures have as their fundamental shortcoming the lack of an
      explicit consideration of the evolutionary context represented by phylogenies.
      Attempts have been made to incorporate phylogenetic considerations into measuring
      biodiversity, but more hypothesis-driven research needs to be done. A specific
      case study is presented of how this added emphasis on phylogeny-based
      biodiversity measurement can influence the way in which research is directed and
      hypotheses are generated. The elucidation of the relationship of biodiversity to
      ecosystem functioning is a very timely concern with the unarguable loss of
      biodiversity this planet is experiencing, whichever way biodiversity is measured.

PMID- 19153994
TI  - Updating the Linnaean heritage: names as tools for thinking about animals and
      plants.

PMID- 19153995
TI  - A day of systems and synthetic biology for non-experts: reflections on day 1 of
      the EMBL/EMBO joint conference on Science and Society.
AB  - From understanding ageing to the creation of artificial membrane-bounded
      'organisms', systems biology and synthetic biology are seen as the latest
      revolutions in the life sciences. They certainly represent a major change of
      gear, but paradigm shifts? This is open to debate, to say the least. For
      scientists they open up exciting ways of studying living systems, of formulating
      the 'laws of life', and the relationship between the origin of life, evolution
      and artificial biological systems. However, the ethical and societal
      considerations are probably indistinguishable from those of human genetics and
      genetically modified organisms. There are some tangible developments just around
      the corner for society, and as ever, our ability to understand the consequences
      of, and manage, our own progress lags far behind our technological abilities.
      Furthermore our educational systems are doing a bad job of preparing the next
      generation of scientists and non-scientists.

PMID- 19153998
TI  - X-chromosome upregulation and inactivation: two sides of the dosage compensation
      mechanism in mammals.
AB  - Mammals have a very complex, tightly controlled, and developmentally regulated
      process of dosage compensation. One form of the process equalizes expression of
      the X-linked genes, present as a single copy in males (XY) and as two copies in
      females (XX), by inactivation of one of the two X-chromosomes in females. The
      second form of the process leads to balanced expression between the X-linked and
      autosomal genes by transcriptional upregulation of the active X in males and
      females. However, not all X-linked genes are absolutely balanced. This review is
      focused on the recent advances in studying the dosage compensation phenomenon in
      mammals.

PMID- 19153999
TI  - The life and death of gene families.
AB  - One of the unique insights provided by the growing number of fully sequenced
      genomes is the pervasiveness of gene duplication and gene loss. Indeed, several
      metrics now suggest that rates of gene birth and death per gene are only 10-40%
      lower than nucleotide substitutions per site, and that per nucleotide, the
      consequent lineage-specific expansion and contraction of gene families may play
      at least as large a role in adaptation as changes in orthologous sequences. While
      gene family evolution is pervasive, it may be especially important in our own
      evolution since it appears that the "revolving door" of gene duplication and loss
      has undergone multiple accelerations in the lineage leading to humans. In this
      paper, we review current understanding of gene family evolution including:
      methods for inferring copy number change, evidence for adaptive expansion and
      adaptive contraction of gene families, the origins of new families and deaths of
      previously established ones, and finally we conclude with a perspective on
      challenges and promising directions for future research.

PMID- 19154000
TI  - A new look at the literature: of understanding, being understood and the role of
      the review.

PMID- 19154001
TI  - Quantitative regulation of alternative splicing in evolution and development.
AB  - Alternative splicing (AS) is a widespread mechanism with an important role in
      increasing transcriptome and proteome diversity by generating multiple different
      products from the same gene. Evolutionary studies of AS have focused primarily on
      the conservation of alternatively spliced sequences or of the AS pattern of those
      sequences itself. Less is known about the evolution of the regulation of AS, but
      several studies, working from different perspectives, have recently made
      significant progress. Here, we categorize the different levels of AS evolution,
      and summarize the studies on evolution of AS regulation, which point to a high
      level of evolutionary conservation of the regulation of AS events conserved
      between related species. This suggests that the quantitative regulation of AS is
      an intrinsic part of AS function. We discuss the potential role of changes in
      developmental regulation of AS as an additional layer in complex gene regulatory
      networks and in the emergence of genetic novelties.

PMID- 19154002
TI  - Beta-catenin and axis formation in planarians.
AB  - In three recent articles it was shown that beta-catenin is crucial for the
      establishment and the maintenance of the overall polarity and especially for the
      character 'posterior' in planarians. If the transcription of the beta-catenin
      gene was silenced by RNA interference, the overall polarity is lost, and in
      regenerating fragments a posterior blastema displays anterior characters by
      forming eyes and anterior ganglia. An attempt is made to integrate these new
      data, well-known older observations, and observations from other regenerating
      systems into an outline of a model that will clarify our current understanding as
      well as highlight areas still to be developed.

PMID- 19154003
TI  - RNA regulation of epigenetic processes.
AB  - There is increasing evidence that dynamic changes to chromatin, chromosomes and
      nuclear architecture are regulated by RNA signalling. Although the precise
      molecular mechanisms are not well understood, they appear to involve the
      differential recruitment of a hierarchy of generic chromatin modifying complexes
      and DNA methyltransferases to specific loci by RNAs during differentiation and
      development. A significant fraction of the genome-wide transcription of non
      protein coding RNAs may be involved in this process, comprising a previously
      hidden layer of intermediary genetic information that underpins developmental
      ontogeny and the differences between species, ecotypes and individuals. It is
      also evident that RNA editing is a primary means by which hardwired genetic
      information in animals can be altered by environmental signals, especially in the
      brain, indicating a dynamic RNA-mediated interplay between the transcriptome, the
      environment and the epigenome. Moreover, RNA-directed regulatory processes may
      also transfer epigenetic information not only within cells but also between cells
      and organ systems, as well as across generations.

PMID- 19154004
TI  - Local auxin production: a small contribution to a big field.
AB  - Auxin is a plant growth regulator involved in diverse fundamental developmental
      responses. Much is now known about auxin transport, via influx and efflux
      carriers, and about auxin perception and its role in gene regulation. Many
      developmental processes are dependent on peaks of auxin concentration and, to
      date, attention has been directed at the role of polar auxin transport in
      generating and maintaining auxin gradients. However, surprisingly little
      attention has focussed on the role and significance of auxin biosynthesis, which
      should be expected to contribute to active auxin pools. Recent reports on the
      function of the YUCCA flavin monooxygenases and a tryptophan aminotransferase in
      Arabidopsis have caused us to look again at the importance of local biosynthesis
      in developmental processes. Many alternative and redundant pathways of auxin
      synthesis exist in many plants and it is emerging that they may function in
      response to environmental cues.

PMID- 19154006
TI  - A sheep in wolf's clothing: do carrion and dung odours of flowers not only
      attract pollinators but also deter herbivores?
AB  - Carrion and dung odours of various flowers have traditionally been considered an
      adaptation for attracting the flies and beetles that pollinate them. While we
      accept the role of such odours in pollinator attraction, we propose that they may
      also have another, overlooked, anti-herbivore defensive function. We suggest that
      such odours may deter mammalian herbivores, especially during the critical period
      of flowering. Carrion odour is a good predictor for two potential dangers to
      mammalian herbivores: (1) pathogenic microbes, (2) proximity of carnivores.
      Similarly, dung odour predicts faeces-contaminated habitats that present high
      risks of parasitism. These are two new types of repulsive olfactory aposematic
      mimicry by plants: (1) olfactory feigning of carcass (thanatosis), a well-known
      behavioural defensive strategy in animals, (2) olfactory mimicry of faeces, which
      also has a defensive visual parallel in animals.

PMID- 19154005
TI  - Microsatellite repeat instability and neurological disease.
AB  - Over 20 unstable microsatellite repeats have been identified as the cause of
      neurological disease in humans. The repeat nucleotide sequences, their location
      within the genes, the ranges of normal and disease-causing repeat length and the
      clinical outcomes differ. Unstable repeats can be located in the coding or the
      non-coding region of a gene. Different pathogenic mechanisms that are
      hypothesised to underlie the diseases are discussed. Evidence is given both from
      studies in simple model systems and from studies on human material and in animal
      models. Since somatic instability might affect the clinical outcome, this is
      briefly touched on. Available data and theories on the timing and mechanisms of
      the repeat instability itself are discussed, along with factors that have been
      observed to affect instability. Finally, the question of why the often harmful
      unstable repeats have been maintained throughout evolution is addressed.

PMID- 19154007
TI  - The Homoscleromorph sponge Oscarella lobularis, a promising sponge model in
      evolutionary and developmental biology: model sponge Oscarella lobularis.
AB  - Sponges branch basally in the metazoan phylogenetic tree and are believed to be
      composed of four distinct lineages with still uncertain relationships. Indeed,
      some molecular studies propose that Homoscleromorpha may be a fourth Sponge
      lineage, distinct from Demospongiae in which they were traditionally classified.
      They harbour many features that distinguish them from other sponges and are more
      evocative of those of the eumetazoans. They are notably the only sponges to
      possess a basement membrane with collagen IV and specialized cell-junctions, thus
      possessing true epithelia. Among Homoscleromorphs, we have chosen Oscarella
      lobularis as a model species. This common and easily accessible sponge is
      characterized by relatively simple histology and cell composition, absence of
      skeleton, and strongly pronounced epithelial structure. In this review, we
      explore the specific features that make O. lobularis a promising homoscleromorph
      sponge model for evolutionary and developmental researches.

PMID- 19154009
TI  - [Structure of ion channels and current-voltage curves].

PMID- 19154008
TI  - The spectra of point mutations in vertebrate genomes.
AB  - In spite of the importance of point mutations for evolution and human diseases,
      their natural spectrum of incidence in different species is not known. Here I
      propose to determine these spectra by comparing consecutive sequence periods in
      stretches of repetitive DNA. The article presents the analysis of more than
      51,000 such point mutations identified by this approach in the genomes of human,
      chimpanzee, rat, mouse, pufferfish, zebrafish, and sea squirt. I propose to
      explain the observed spectra by auto-mutagenic mechanisms of genome variation
      involving the inter-conversions of nucleotides, single base-pair inversions and
      their combinations.

PMID- 19154010
TI  - Current world literature. Micronutrients.

PMID- 19154011
TI  - Current world literature. Functional foods.

PMID- 19154012
TI  - Self-diffusion coefficient in smoothed dissipative particle dynamics.
AB  - Smoothed dissipative particle dynamics (SDPD) is a novel coarse grained method
      for the numerical simulation of complex fluids. It has considerable advantages
      over more traditional particle-based methods. In this paper we analyze the self
      diffusion coefficient D of a SDPD solvent by using the strategy proposed by Groot
      and Warren [J. Chem. Phys. 107, 4423 (1997)]. An analytical expression for D in
      terms of the model parameters is developed and verified by numerical simulations.

PMID- 19154013
TI  - The self-referential method for linear rigid bodies: application to hard and
      Lennard-Jones dumbbells.
AB  - The self-referential (SR) method incorporating thermodynamic integration (TI)
      [Sweatman et al., J. Chem. Phys. 128, 064102 (2008)] is extended to treat systems
      of rigid linear bodies. The method is then applied to obtain the canonical
      ensemble Helmholtz free energy of the alpha-N(2) and plastic face centered cubic
      phases of systems of hard and Lennard-Jones dumbbells using Monte Carlo
      simulations. Generally good agreement with reference literature data is obtained,
      which indicates that the SR-TI method is potentially very general and robust.

PMID- 19154014
TI  - Solving non-Born-Oppenheimer Schrodinger equation for hydrogen molecular ion and
      its isotopomers using the free complement method.
AB  - The Schrodinger equations for the hydrogen molecular ion (H(2)(+)) and its
      isotopomers (D(2)(+), T(2)(+), HD(+), HT(+), and DT(+)) were solved very
      accurately using the free iterative complement interaction method, which is
      referred to in short as the free complement (FC) method, in the non-Born
      Oppenheimer (non-BO) level, i.e., in the nonrelativistic limit. Appropriate
      complement functions for both electron and nuclei were generated automatically by
      the FC procedure with the use of the non-BO Hamiltonian, which contains both
      electron and nuclear operators on an equal footing. Quite accurate results were
      obtained not only for the ground state but also for the vibronic excited states.
      For example, we obtained the ground-state energy of H(2)(+) as -0.597 139 063 123
      405 074 834 134 096 025 974 142 a.u., which is variationally the best in
      literature. The difference in the nuclear spin states of (1)S (para) and (3)P
      (ortho) of H(2)(+) and some physical expectation values for several of the
      isotopomers shown above were also examined. The present study is the first
      application of the FC method to molecular systems with the non-BO Hamiltonian.

PMID- 19154015
TI  - Moving least-squares enhanced Shepard interpolation for the fast marching and
      string methods.
AB  - The number of the potential energy calculations required by the quadratic string
      method (QSM), and the fast marching method (FMM) is significantly reduced by
      using Shepard interpolation, with a moving least squares to fit the higher-order
      derivatives of the potential. The derivatives of the potential are fitted up to
      fifth order. With an error estimate for the interpolated values, this moving
      least squares enhanced Shepard interpolation scheme drastically reduces the
      number of potential energy calculations in FMM, often by up 80%. Fitting up
      through the highest order tested here (fifth order) gave the best results for all
      grid spacings. For QSM, using enhanced Shepard interpolation gave slightly better
      results than using the usual second order approximate, damped Broyden-Fletcher
      Goldfarb-Shanno updated Hessian to approximate the surface. To test these methods
      we examined two analytic potentials, the rotational dihedral potential of alanine
      dipeptide and the S(N)2 reaction of methyl chloride with fluoride.

PMID- 19154016
TI  - Unrestricted algebraic diagrammatic construction scheme of second order for the
      calculation of excited states of medium-sized and large molecules.
AB  - An unrestricted version of the algebraic diagrammatic construction (ADC) scheme
      of the polarization propagator in second order perturbation theory [UADC(2)] is
      derived via the intermediate state representation. The accuracy of the extended
      UADC(2)-x approach is evaluated by comparison of computed excitation energies of
      11 medium-sized radicals with their corresponding experimental literature values
      and with excitation energies computed at equation-of-motion-CCSD (coupled
      clusters singles and doubles) level of theory. Overall, our numerical tests show
      that UADC(2)-x exhibits an averaged mean deviation in the excitation energies of
      only 0.3-0.4 eV compared to experimental gas phase data. It provides thus an
      alternative to coupled-cluster based approaches for the calculation of excited
      states of medium-sized open-shell molecules.

PMID- 19154017
TI  - Efficient global representations of potential energy functions: trajectory
      calculations of bimolecular gas-phase reactions by multiconfiguration molecular
      mechanics.
AB  - Multiconfiguration molecular mechanics (MCMM) was previously applied to calculate
      potential energies, gradients, and Hessians along a reaction path and in the
      large-curvature tunneling swath, and it was shown that one could calculate
      variational transition state theory rate constants with optimized
      multidimensional tunneling without requiring more than a few electronic structure
      Hessians. It was also used for molecular dynamics simulations of liquid-phase
      potentials of mean force as functions of a reaction coordinate. In the present
      article we present some improvements to the formalism and also show that with
      these improvements we can use the method for the harder problem of trajectory
      calculations on gas-phase bimolecular reactive collisions. In particular, we
      apply the MCMM algorithm to the model reaction OH + H(2) --> H(2)O + H, for which
      we construct the global full-dimensional interpolated potential energy surfaces
      with various numbers of electronic structure Hessians and various molecular
      mechanics force fields, and we assess the quality of these fits by quasiclassical
      trajectory calculations. We demonstrate that chemical accuracy (1-2 kcal/mol) can
      be reached for a MCMM potential in dynamically important regions with a fairly
      small number of electronic structure Hessians. We also discuss the origins of the
      errors in the interpolated energies and a possible way to improve the accuracy.

PMID- 19154018
TI  - Chemical reaction surface vibrational frequencies evaluated in curvilinear
      internal coordinates: Application to H + CH(4) <==> H(2) + CH(3).
AB  - We consider the general problem of vibrational analysis at nonglobally optimized
      points on a reduced dimensional reaction surface. We discuss the importance of
      the use of curvilinear internal coordinates to describe molecular motion and
      derive a curvilinear projection operator to remove the contribution of nonzero
      gradients from the Hessian matrix. Our projection scheme is tested in the context
      of a two-dimensional quantum scattering calculation for the reaction H + CH(4) -
      > H(2) + CH(3) and its reverse H(2) + CH(3) --> H + CH(4). Using zero-point
      energies calculated via rectilinear and curvilinear projections we construct two
      two-dimensional, adiabatically corrected, ab initio reaction surfaces for this
      system. It is shown that the use of curvilinear coordinates removes unphysical
      imaginary frequencies observed with rectilinear projection and leads to
      significantly improved thermal rate constants for both the forward and reverse
      reactions.

PMID- 19154019
TI  - Efficient sampling for ab initio Monte Carlo simulation of molecular clusters
      using an interpolated potential energy surface.
AB  - An approach is developed to enhance sampling for ab initio Monte Carlo and ab
      initio path integral Monte Carlo calculations of molecular clusters by utilizing
      an approximate potential as a guide to move in the configuration space more
      efficiently. The interpolated potential energy obtained by the moving least
      squares method is used as an approximate potential, and this scheme is applied to
      a water molecule and small protonated water clusters (H(3)O(+), H(5)O(2)(+)). It
      is found that the statistical errors are reduced by almost a factor of 3 in most
      calculations, which translates into a reduction in the computational cost by an
      order of magnitude. We also provide an automatic scheme where the ab initio data
      obtained during the simulation is added to the reference data set of
      interpolation dynamically, which further speeds up the convergence.

PMID- 19154020
TI  - Time evolution of dynamic propensity in a model glass former: the interplay
      between structure and dynamics.
AB  - By means of the isoconfigurational method, we calculate the change in the
      propensity for motion that the structure of a glass-forming system experiences
      during its relaxation dynamics. The relaxation of such a system has been
      demonstrated to evolve by means of rapid crossings between metabasins of its
      potential energy surface (a metabasin being a group of mutually similar, closely
      related structures which differ markedly from other metabasins), as collectively
      relaxing units (d-clusters) take place. We now show that the spatial distribution
      of propensity in the system does not change significantly until one of these d
      clusters takes place. However, the occurrence of a d-cluster clearly decorrelates
      the propensity of the particles, thus ending up with the dynamical influence of
      the structural features proper of the local metabasin. We also show an important
      match between particles that participate in d-clusters and that which show high
      changes in their propensity.

PMID- 19154021
TI  - Role of noncollinear magnetization for the first-order electric-dipole
      hyperpolarizability at the four-component Kohn-Sham density functional theory
      level.
AB  - The quadratic response function has been derived and implemented at the adiabatic
      four-component Kohn-Sham density functional theory level with inclusion of
      noncollinear spin magnetization and gradient corrections in the exchange
      correlation functional-a work that is an extension of our previous report where
      magnetization dependencies in the exchange-correlation functional were ignored
      [J. Henriksson, T. Saue, and P. Norman, J. Chem. Phys. 128, 024105 (2008)]. The
      electric-field induced second-harmonic generation experiments on CF(3)Cl and
      CF(3)Br are addressed by a determination of beta(-2omega;omega, omega) for a
      wavelength of 694.3 nm, and the same property is also determined for CF(3)I. The
      relativistic effects on the static hyperpolarizability for the series of
      molecules amount to 1%, 5%, and 9%, respectively. At the experimental wavelength,
      the contributions to beta due to the magnetization dependence in the exchange
      correlation functional are negligible for CF(3)Cl and CF(3)Br and small for
      CF(3)I. The noticeable effect of magnetization in the latter case is attributed
      to a near two-photon resonance with the excited state 1 (3)E (nonrelativistic
      notation). It is emphasized, however, that the effect of magnetization on beta
      for CF(3)I is negligible both in comparison to the total relativistic correction
      as well as to the effects of electron correlation. It is concluded that, in
      calculations of hyperpolarizabilities under nonresonant conditions, the
      magnetization dependence in the exchange-correlation functional may be ignored.

PMID- 19154022
TI  - A theoretical study of linear beryllium chains: full configuration interaction.
AB  - We present a full configuration interaction study of Be(N) (N=2,3,4,5) linear
      chains. A comparative study of the basis-set effect on the reproduction of the
      energy profile has been reported. In particular, the 3s1p, 4s2p, 4s2p1d, 5s3p2d,
      and 5s3p2d1f bases were selected. For the smallest chains (i.e., Be(2) and
      Be(3)), smaller basis sets give dissociative energy profiles, so large basis set
      is demanded for the reproduction of equilibrium minima in the structures. For
      Be(4) and Be(5) linear chains, the energy profiles show a minimum also by using
      the smallest basis sets, but the largest ones give a much stronger stabilization
      energy. For all the structures, two spin states have been studied: the singlet
      and the triplet. It is shown that the energy separation of the two states, in the
      equilibrium region, is small and decays exponentially with respect to the number
      of atoms in the chain. Finally an interpolative technique allowing for the
      estimation of the long-chain parameters from shorter ones is presented.

PMID- 19154023
TI  - Biradicalic excited states of zwitterionic phenol-ammonia clusters.
AB  - Phenol-ammonia clusters with more than five ammonia molecules are proton
      transferred species in the ground state. In the present work, the excited states
      of these zwitterionic clusters have been studied experimentally with two-color
      pump probe methods on the nanosecond time scale and by ab initio electronic
      structure calculations. The experiments reveal the existence of a long-lived
      excited electronic state with a lifetime in the 50-100 ns range, much longer than
      the excited state lifetime of bare phenol and small clusters of phenol with
      ammonia. The ab initio calculations indicate that this long-lived excited state
      corresponds to a biradicalic system, consisting of a phenoxy radical that is
      hydrogen bonded to a hydrogenated ammonia cluster. The biradical is formed from
      the locally excited state of the phenolate anion via an electron transfer
      process, which neutralizes the charge separation of the ground state zwitterion.

PMID- 19154024
TI  - A study of the ground and excited states of Al3 and Al3(-). I. 488 nm anion
      photoelectron spectrum.
AB  - The vibrationally resolved, 488 nm anion photoelectron spectrum of aluminum
      trimer displays transitions from two electronic states of Al(3)(-) to four states
      of Al(3). Franck-Condon analyses of the spectra in the independent harmonic
      oscillator, parallel mode approximation provide information concerning
      equilibrium bond length and bond angle differences among the observed states. The
      electron affinity of Al(3) is measured to be 1.916+/-0.004 eV. In the X
      (2)A(1)(') Al(3) ground state, fundamental symmetric stretching (nu(1)) and
      bending (nu(2)) vibrational frequencies are 357+/-10 and 240+/-10 cm(-1). In the
      X (1)A(1)(') Al(3)(-) ground state, these values are 365+/-15 and 257+/-15 cm(
      1), and the equilibrium bond lengths are the same as those of Al(3) to within
      0.02 A. The transition between the Al(3)(-) and Al(3) ground states displays only
      weak activity in the bending mode, consistent with essentially D(3h) structures
      for both states. An excited (3)B(2) Al(3)(-) state at 0.409+/-0.004 eV (T(0)) has
      vibrational frequencies of 330+/-20 (nu(1)) and 200+/-10 cm(-1) (nu(2)). This
      C(2v) state has a 65+/-1 degree apex bond angle and its two equal bond lengths
      are within 0.01 A of the ground state value. Liquid nitrogen cooling of the
      downstream portion of the approximately 60 cm long, 0.4-0.7 Torr flow tube anion
      source increases the observed relative population of this excited triplet state
      among the sampled anions, evidently slowing its relaxation to the singlet ground
      state. A (2)A(2)(") excited state of Al(3) lies 0.192+/-0.004 eV above the ground
      state and has frequencies of 315+/-15 (nu(1)) and 197+/-10 cm(-1) (nu(2)) and
      bonds 0.10+/-0.03 A longer than in the ground state. A (4)A(2) Al(3) excited
      state at 0.300+/-0.004 eV displays 315+/-15 (nu(1)) and 140+/-10 cm(-1) (nu(2))
      vibrational frequencies. The Franck-Condon analysis of this state, which is
      accessed only from the (3)B(2) anion, indicates a C(2v) structure with a 69+/-2
      degree apex bond angle and bonds 0.06+/-0.02 A longer than in the ground state. A
      (2)B(2) Al(3) excited state at 0.706+/-0.005 eV is also accessed from the (3)B(2)
      anion. The lack of vibrational features observable over overlapping transitions
      indicates similar structures for the (2)B(2) and (3)B(2) states. Primary
      stretching force constants (mdyn/A) are reported for the Al(3)(-) (0.70+/-0.06)
      and Al(3) (0.63+/-0.04) ground states and for three excited states. In the
      following paper, computational predictions for the ground and excited states of
      Al(3)(-) and Al(3) are reported and compared with these results.

PMID- 19154025
TI  - A study of the ground and excited states of Al3 and Al3(-). II. Computational
      analysis of the 488 nm anion photoelectron spectrum and a reconsideration of the
      Al3 bond dissociation energy.
AB  - Computational results are reported for the ground and low-lying excited
      electronic states of Al(3)(-) and Al(3) and compared with the available
      spectroscopic data. In agreement with previous assignments, the six
      photodetachment transitions observed in the vibrationally resolved 488 nm
      photoelectron spectrum of Al(3)(-) are assigned as arising from the ground X
      (1)A(1) (')((1)A(1)) and excited (3)B(2) states of Al(3)(-) and accessing the
      ground X (2)A(1)(')((2)A(1)) and excited (2)A(2)(")((2)B(1)), (4)A(2), and
      (2)B(2) states of Al(3) (with C(2v) labels for D(3h) states in parentheses).
      Geometries and vibrational frequencies obtained by PBE0 hybrid density functional
      calculations using the 6-311+G(3d2f) basis set and energies calculated using
      coupled cluster theory with single and double excitations and a quasiperturbative
      treatment of connected triple excitations (CCSD(T)) with the aug-cc-pVxZ {x=D, T,
      Q} basis sets with exponential extrapolation to the complete basis set limit are
      in good agreement with experiment. Franck-Condon spectra calculated in the
      harmonic approximation, using either the Sharp-Rosenstock-Chen method which
      includes Duschinsky rotation or the parallel-mode Hutchisson method, also agree
      well with the observed spectra. Possible assignments for the higher-energy bands
      observed in the previously reported UV photoelectron spectra are suggested.
      Descriptions of the photodetachment transition between the Al(3)(-) and Al(3)
      ground states in terms of natural bond order (NBO) analyses and total electron
      density difference distributions are discussed. A reinterpretation of the
      vibrational structure in the resonant two-photon ionization spectrum of Al(3) is
      proposed, which supports its original assignment as arising from the X (2)A(1)(')
      ground state, giving an Al(3) bond dissociation energy, D(0)(Al(2)-Al), of
      2.403+/-0.001 eV. With this reduction by 0.3 eV from the currently recommended
      value, the present calculated dissociation energies of Al(3), Al(3)(-), and
      Al(3)(+) are consistent with the experimental data.

PMID- 19154026
TI  - Regular vibrational state progressions at the dissociation limit of SCCl2.
AB  - We observe sharp features in the vibrational spectrum of SCCl(2) at and above its
      two lowest-lying dissociation limits. Highly regular vibrational progressions
      persist at dissociation, as in some smaller molecules studied previously by
      others. Nearly all of the SCCl(2) transitions studied by stimulated emission
      pumping can be assigned and fitted by a simple effective Hamiltonian without
      resonance terms, up to a total vibrational excitation of 36 quanta. The character
      of the highly excited vibrational wave functions is not normal mode-like, but it
      nonetheless arises gradually from the normal modes as the energy increases. The
      number of sharp vibrational features observed matches a scaling model that
      predicts localization of nearly all vibrational states near dissociation as the
      size of a polyatomic molecule increases.

PMID- 19154027
TI  - Penning ionization electron spectra of pyrene, chrysene, and coronene in
      collision with metastable He(2 3S) atoms in the gas phase.
AB  - Penning ionization electron spectra (PIES) of pyrene (C(16)H(10)), chrysene
      (C(18)H(12)), and coronene (C(24)H(12)) in the gas phase are recorded using
      metastable He(*)(2 (3)S) atoms. The assignments of PIES are presented based on
      the outer valence Green's function calculations with the correlation consistent
      polarized valence triple-zeta basis sets and the exterior electron density
      calculations of contributing molecular orbitals. The definite positions of all of
      the pi bands in the PIES are identified making use of the large PIES cross
      sections. Broad bands are observed in low-electron-energy regions for chrysene
      and coronene and are ascribed to ionization processes of non-Koopmans types from
      sigma orbitals. The anisotropic interaction potential energy surfaces for the
      colliding systems are obtained from ab initio model potentials for the related
      systems with similar outer valences Li(2 (2)S) + C(16)H(10), C(18)H(12), and
      C(24)H(12), respectively. The attractive well depths in the out-of-plane
      directions are found to be similar between these molecules, and the repulsive
      walls embrace the in-plane perimeters uniformly. Collision energy dependencies
      for partial Penning ionization cross sections and negative peak shifts in PIES
      for chrysene support these anisotropic interactions. Effects from thermal
      populations in low-frequency vibrational modes are estimated to be minor in one
      electron ionization processes.

PMID- 19154028
TI  - Adiabatic invariance along the reaction coordinate.
AB  - In a two-dimensional space where a point particle interacts with a diatomic
      fragment, the action integral contour integral of p(theta) d theta (where theta
      is the angle between the fragment and the line of centers and p(theta) its
      conjugate momentum) is an adiabatic invariant. This invariance is thought to be a
      persistent dynamical constraint. Indeed, its classical Poisson bracket with the
      Hamiltonian is found to vanish in particular regions of the potential energy
      surface: asymptotically, at equilibrium geometries, saddle points, and inner
      turning points, i.e., at remarkable situations where the topography of the
      potential energy surface is locally simple. Studied in this way, the adiabatic
      decoupling of the reaction coordinate is limited to disjoint regions. However, an
      alternative view is possible. The invariance properties of entropy (as defined in
      information theory) can be invoked to infer that dynamical constraints that are
      found to operate locally subsist everywhere, throughout the entire reactive
      process, although with a modified expression.

PMID- 19154029
TI  - Ab initio study of stoichiometric gallium phosphide clusters.
AB  - We have studied the static dipole polarizability of stoichiometric gallium
      phosphide clusters (Ga(n)P(n) with n=2-5) by employing various ab initio wave
      function based methods as well as density functional theory/time dependent
      density functional theory (DFT/TDDFT). The calculation of polarizability within
      DFT/TDDFT has been carried out by employing different exchange-correlation
      functionals, ranging from simple local density approximation to an asymptotically
      correct model potential-statistical average of orbital potential (SAOP) in order
      to study their influences. The values obtained by using the model potential-SAOP
      are lower than those obtained by local density approximation and generalized
      gradient approximation. A systematic analysis of our results obtained using the
      DFT/TDDFT with several exchange-correlation functionals shows that the values of
      polarizability obtained within generalized gradient approximation by using Perdew
      Burke-Ernzerhof exchange with Lee-Yang-Parr correlation functional and Perdew
      Burke-Ernzerhof exchange-correlation functionals are the closest to the
      corresponding results from Moller-Plesset perturbation theory. We have found that
      the value of average static dipole polarizability per atom reaches the bulk limit
      from the above as the size of the clusters increases.

PMID- 19154030
TI  - On the ultraviolet photofragmentation of CH3Xe+.
AB  - The multireference spin-orbit configuration interaction method is employed to
      calculate potential energy surfaces for the ground and low-lying excited states
      of the CH(3)Xe(+) cation as functions of the Xe-C bond length and the Xe-C-H
      angle. It is shown that the X (1)A(1) ground state of CH(3)Xe(+) is well bound
      (D(e)=1.78 eV) and dissociates to the CH(3)(+)(X (1)A(1)(')) + Xe((1)S) limit. In
      contrast, all lowest excited states of CH(3)Xe(+) are repulsive in the Franck
      Condon region and converge to the strongly spin-split CH(3)(X (2)A(")) +
      Xe(+)((2)P(3/2,1/2)) asymptotes. Transition dipole moments for the low-lying
      valence states are computed at the X (1)A(1) equilibrium geometry. It is shown
      that the first absorption continuum (A band) of CH(3)Xe(+) is dominated by the
      parallel (3)Q(0(+))(A(1)) <-- X (1)A(1) transition, which leads to the CH(3) +
      Xe(+)((2)P(3/2)) dissociation products. The perpendicular transitions to the
      (1)Q(E), (3)Q(1)(E), and (3)A(1)(E) states are found to be significantly weaker.
      The CH(3)Xe(+) photodissociation process in its A band is analyzed on the basis
      of the computed data and compared with the photodissociation of the isovalent
      RgH(+) (Rg = Ar,Kr,Xe), HI, and CH(3)I systems.

PMID- 19154031
TI  - Few-cycle laser pulses to obtain spatial separation of OHF- dissociation
      products.
AB  - In a two-part theoretical study, field-free orientation of OHF(-) is achieved by
      means of moderately intense half-cycle, infrared laser pulses. In the first step,
      a short linearly polarized pulse excites a superposition of rigid rotor
      rotational eigenstates via interaction with the permanent dipole moment of OHF(
      ). After the field has been switched off, pronounced molecular orientation is
      observed for several picoseconds. In the second step, femtosecond few-cycle laser
      pulses are applied to the oriented system to steer vibrational dynamics, modeled
      by anharmonic vibrational wave functions calculated on a potential energy surface
      obtained with unrestricted fourth order Moller-Plesset ab initio calculations.
      The result is selective bond breaking of OHF, followed by the spatial separation
      of dissociation products in the space-fixed frame. Due to revivals in the
      rotational wavepacket, product yields can be enhanced over long times.

PMID- 19154032
TI  - Quasiequilibrium states in thermotropic liquid crystals studied by multiple
      quantum NMR.
AB  - Previous work showed that by means of the Jeener-Broekaert (JB) experiment, two
      quasiequilibrium states can be selectively prepared in the proton spin system of
      thermotropic nematic liquid crystals (LCs) in a strong magnetic field. The
      similarity of the experimental results obtained in a variety of LC in a broad
      Larmor frequency range, with crystal hydrates, supports the assumption that also
      in LC the two spin reservoirs, into which the Zeeman order is transferred,
      originate in the dipolar energy and that they are associated with a separation in
      energy scales: A constant of motion related to the stronger dipolar interactions
      (S), and a second one (W) corresponding to the secular part of the weaker dipolar
      interactions with regard to the Zeeman and the strong dipolar part. We study the
      nature of these quasi-invariants in nematic 5CB (4(')-pentyl-4-biphenyl
      carbonitrile) and measure their relaxation times by encoding the multiple-quantum
      coherences of the states following the JB pulse pair on two orthogonal bases, Z
      and X. The experiments were also performed in powder adamantane at 301 K which is
      used as a reference compound having only one dipolar quasi-invariant. We show
      that the evolution of the quantum states during the buildup of the
      quasiequilibrium state in 5CB prepared under the S condition is similar to the
      case of powder adamantane and that their quasiequilibrium density operators have
      the same tensor structure. In contrast, the second constant of motion, whose
      explicit operator form is not known, involves a richer composition of multiple
      quantum coherences of even order on the X basis, in consistency with the
      truncation inherent in its definition. We exploited the exclusive presence of
      coherences of +/-4,+/-6,+/-8, besides 0 and +/-2 under the W condition to measure
      the spin-lattice relaxation time T(W) accurately, so avoiding experimental
      difficulties that usually impair dipolar order relaxation measurement such as
      Zeeman contamination at high fields and also superposition of the different quasi
      invariants. This procedure opens the possibility of measuring the spin-lattice
      relaxation of a quasi-invariant independent of the Zeeman and S reservoirs, so
      incorporating a new relaxation parameter useful for studying the complex
      molecular dynamics in mesophases. In fact, we report the first measurement of
      T(W) in a LC at high magnetic fields. Comparison of the obtained value with the
      one corresponding to a lower field (16 MHz) points out that the relaxation of the
      W-order strongly depends on the intensity of the external magnetic field,
      similarly to the case of the S reservoir, indicating that the relaxation of the W
      quasi-invariant is also governed by the cooperative molecular motions.

PMID- 19154033
TI  - A first principles investigation of water dipole moment in a defective continuous
      hydrogen bond network.
AB  - First principles molecular dynamics simulations of an aqueous solution salt
      system at finite concentration containing both Na(+) and Cl(-) ions show that a
      change in the distribution of the molecular dipole moment of H(2)O monomers
      appears when ions are present in solution. Simulations suggest a lowering of the
      dipole moments of the water molecules in the solvation shells of Na(+) and Cl(-)
      as compared to the pure water case, while the dipoles of the rest of the
      molecules are hardly affected. However, finer analysis in terms of the Wannier
      centers distribution suggests a change in the electronic structure of the water
      molecules even in the bulk. Also a change of the H-bond network arrangement was
      found and correlation between dipole and MOH parameter evidences such subtle
      effects, suggesting a lowering of tetrahedral order in salty solutions. All these
      changes can be related to observable quantities such as the infrared spectra thus
      allowing for a rationalization of the experimental outcome on neutral aqueous
      solutions.

PMID- 19154034
TI  - Self-diffusion coefficient of two-center Lennard-Jones fluids: molecular
      simulations and free volume theory.
AB  - A comprehensive investigation is conducted to study the thermodynamics,
      structure, and mean free volume of rigid two-center Lennard-Jones fluids through
      Monte Carlo simulations. For a large number of states, the self-diffusion
      coefficient is computed using the following two different approaches: the
      equilibrium molecular dynamics simulation method and the modified Cohen-Turnbull
      theory. The effects of the bond elongation on different thermophysical properties
      are studied. The generic van der Waals theory, which has recently been extended
      to rigid polyatomic fluids [A. Eskandari Nasrabad and R. Laghaei, J. Chem. Phys.
      125, 154505 (2006)], is used to compute the mean free volume needed in the
      modified Cohen-Turnbull theory. The effective site diameter is computed using the
      virial minimization method and the results are applied within the generic van der
      Waals theory. The Gibbs ensemble Monte Carlo simulation technique is applied to
      determine the location of the fluid phase envelope. The NVT Monte Carlo
      simulation method is then utilized to compute the equation of state and the
      correlation functions appearing in the generic van der Waals theory. It appears
      that the logarithm of the mean free volume versus density is almost linear at
      rho>rho(c) independent of the bond length, which suggests a universal behavior.
      The self diffusion coefficient results of the modified Cohen-Turnbull theory are
      analyzed in detail.

PMID- 19154035
TI  - Preferential solvation of spherical ions in binary DMSO/benzene mixtures.
AB  - We consider a new qualitative approach for treating theoretically the solvation
      of single-atomic ionic solutes in binary mixtures of polar and nonpolar aprotic
      solvents. It is based on the implicit continuum electrostatic model of the
      solvent mixture involving distance-dependent dielectric permittivity epsilon(R)
      (where R is the distance from the ion) and local concentrations C(1)(R) and
      C(2)(R) of the solvent ingredients. For a given R, the condition for local
      thermodynamic equilibrium provides the transcendental equation for explicitly
      establishing the permittivity and concentration profiles. Computations performed
      with real Cl(-) and model Cl(+) ions as solutes in benzene/DMSO mixtures are
      compared with the molecular dynamics simulations of the same systems. A
      significant discrepancy of molecular and continuum results is revealed for the
      concentration profiles in the close vicinity of the ion boundary, although the
      general trends are similar. The continuum methodology cannot account for the
      formation of rigid solvent structures around ions, which is most significant for
      the case of Cl(+). Such defect, however, proves to become of less importance in
      calculations of the solvation free energy, which are quite satisfactory for Cl(-)
      ion. Free energy calculations for Cl(+) are less successful in the range of low
      DMSO concentration.

PMID- 19154036
TI  - Advanced dielectric continuum model of preferential solvation.
AB  - A continuum model for solvation effects in binary solvent mixtures is formulated
      in terms of the density functional theory. The presence of two variables, namely,
      the dimensionless solvent composition y and the dimensionless total solvent
      density z, is an essential feature of binary systems. Their coupling, hidden in
      the structure of the local dielectric permittivity function, is postulated at the
      phenomenological level. Local equilibrium conditions are derived by a variation
      in the free energy functional expressed in terms of the composition and density
      variables. They appear as a pair of coupled equations defining y and z as spatial
      distributions. We consider the simplest spherically symmetric case of the Born
      type ion immersed in the benzene/dimethylsulfoxide (DMSO) solvent mixture. The
      profiles of y(R) and z(R) along the radius R, which measures the distance from
      the ion center, are found in molecular dynamics (MD) simulations. It is shown
      that for a given solute ion z(R) does not depend significantly on the composition
      variable y. A simplified solution is then obtained by inserting z(R), found in
      the MD simulation for the pure DMSO, in the single equation which defines y(R).
      In this way composition dependences of the main solvation effects are
      investigated. The local density augmentation appears as a peak of z(R) at the ion
      boundary. It is responsible for the fine solvation effects missing when the
      ordinary solvation theories, in which z=1, are applied. These phenomena, studied
      for negative ions, reproduce consistently the simulation results. For positive
      ions the simulation shows that z>>1 (z=5-6 at the maximum of the z peak), which
      means that an extremely dense solvation shell is formed. In such a situation the
      continuum description fails to be valid within a consistent parametrization.

PMID- 19154037
TI  - Deuteron spectra, spin-lattice relaxation, and stimulated echoes in ice II.
AB  - (2)H NMR spectra, spin-lattice relaxation, and stimulated echoes have been
      measured in polycrystalline ice II in the temperature range of 84-145 K at
      ambient pressure. From the spectra we obtain the quadrupole coupling constant in
      ice II, e(2)qQ/h = (225.7+/-1.2) kHz, and the asymmetry parameter, eta = 0.118+/
      0.006. At 145 K, a phase transition of ice II into ice I(c) is observed by a
      change of both, its spectral and relaxation behavior. The spin-lattice relaxation
      in ice II is bimodal, showing two components of approximately the same weight.
      The fast relaxing part of the recovery curve progresses monoexponentially and the
      temperature dependence of its mean relaxation time corresponds to an unusually
      low activation energy of 2.3 kJ mol(-1). The slowly relaxing part, displaying
      average relaxation times of about 4000 s, is significantly stretched with a
      Kohlrausch parameter of 0.6 and shows no temperature dependence. The stimulated
      echo experiments show a temperature independent correlation decay. The analysis
      of intermediate states indicates that no small-angle motions are involved in the
      underlying process. Both findings exclude an interpretation in terms of molecular
      motion. Instead, spin diffusion in the deuteron system has to be considered as
      the origin of the phenomena observed in the stimulated echo experiments.

PMID- 19154038
TI  - Experimental and computational studies on collective hydrogen dynamics in ammonia
      borane: incoherent inelastic neutron scattering.
AB  - Incoherent inelastic neutron scattering is used to probe the effects of
      dihydrogen bonding on the vibrational dynamics in the molecular crystal of
      ammonia borane. The thermal neutron energy loss spectra of (11)B enriched ammonia
      borane isotopomers ((11)BH(3)NH(3), (11)BD(3)NH(3), and (11)BH(3)ND(3)) are
      presented and compared to the vibrational power spectrum calculated using ab
      initio molecular dynamics. A harmonic vibrational analysis on NH(3)BH(3) clusters
      was also explored to check for consistency with experiment and the power
      spectrum. The measured neutron spectra and computed ab initio power spectrum
      compare extremely well (50-500 cm(-1)). Some assignment of modes to simple
      harmonic motion, e.g., NH(3) and BH(3) torsion in the molecular crystal is
      possible, and it is confirmed that the lowest modes are dominated by collective
      motion. We show that the vibrational dynamics as modeled with ab initio molecular
      dynamics provides a more complete description of anharmonic and collective
      dynamics in the low frequency region of the inelastic incoherent neutron
      scattering spectra when compared to the conventional harmonic approach.

PMID- 19154039
TI  - Melting of defective Cu with stacking faults.
AB  - We conduct classical molecular dynamics simulations to investigate isobaric
      melting of defective Cu solids with only one type of defect: intrinsic or
      extrinsic stacking faults. We characterize bulk melting and nucleation of melt in
      terms of order parameters, liquid cluster analysis, and the mean-first-passage
      time method. The stacking faults induce negligible reduction in the temperature
      at melting, and the amount of superheating in these defective solids is the same
      as the perfect solids. Both homogeneous and heterogeneous nucleations of melt are
      observed. The existence of the stacking faults only slightly increases the
      nucleation rate and the probability of nucleation at heterogeneous nucleation
      sites. Such observations can be attributed to the low energy of the stacking
      faults and the extremely high heating rates in molecular dynamics simulations.
      These results underscore the necessity of considering the effects of rate and
      defect when interpreting experimental and simulation results as regards, e.g.,
      phase boundaries.

PMID- 19154040
TI  - Optimized equation of the state of the square-well fluid of variable range based
      on a fourth-order free-energy expansion.
AB  - The free energy of square-well (SW) systems of hard-core diameter sigma with
      ranges 1 < or = lambda < or = 3 is expanded in a perturbation series. This
      interval covers most ranges of interest, from short-ranged SW fluids (lambda
      approximately 1.2) used in modeling colloids to long ranges (lambda approximately
      3) where the van der Waals classic approximation holds. The first four terms are
      evaluated by means of extensive Monte Carlo simulations. The calculations are
      corrected for the thermodynamic limit and care is taken to evaluate and to
      control the various sources of error. The results for the first two terms in the
      series confirm well-known independent results but have an increased estimated
      accuracy and cover a wider set of well ranges. The results for the third- and
      fourth-order terms are novel. The free-energy expansion for systems with short
      and intermediate ranges, 1 < or = lambda < or = 2, is seen to have properties
      similar to those of systems with longer ranges, 2 < or = lambda < or = 3. An
      equation of state (EOS) is built to represent the free-energy data. The
      thermodynamics given by this EOS, confronted against independent computer
      simulations, is shown to predict accurately the internal energy, pressure,
      specific heat, and chemical potential of the SW fluids considered and for
      densities 0 < or = rho sigma(3) < or = 0.9 including subcritical temperatures.
      This fourth-order theory is estimated to be accurate except for a small region at
      high density, rho sigma(3) approximately 0.9, and low temperature where terms of
      still higher order might be needed.

PMID- 19154041
TI  - Probing the strength of the system-bath interaction by three-pulse photon echoes.
AB  - We explore how the width of the three-pulse photon echo signal at long population
      times can be used to determine the strength of the system-bath interaction. Using
      simulation with finite pulses we show that a simple relation exist between the
      width of the echo signal, the coupling strength, and the pulse autocorrelation.
      The derived model is applied to Rhodamine 6G in alcoholic solution, a paradigm
      system for the study of solvation dynamics, and the results are compared to
      conventional methods. The independently determined coupling strength forms the
      basis for a computationally inexpensive route to determine the entire spectral
      density, the key parameter when considering system-bath interactions. Our method
      allows us to accurately estimate the relative amplitude of fast and slow
      components in the correlation function using only impulsive limit simulations. We
      show that the peak shift significantly overestimates the amplitude of the fastest
      decay component for our experimental data. Changing solvent from methanol to 1
      hexanol we observe a narrowing of the width of the echo profile. The changes in
      the echo width allow us to estimate the changes of the coupling strength in
      various solvents.

PMID- 19154042
TI  - Solute migration caused by excited state absorptions.
AB  - Using the Z-scan technique, we find that migration of chloroaluminum
      phthalocyanine in liquid ethanol can be induced by the absorption of a 19 ps
      laser pulse with energy exceeding a threshold but not by that of a 2.8 ns pulse
      depositing more energy at the solute molecules. Considering each solute molecule
      as an oscillator confined within a potential well, we explain, in accordance with
      the five-energy-band model, that solute molecules excited by a 19 ps pulse retain
      more translational excess energy to overcome the potential well barrier compared
      with those excited by a 2.8 ns pulse of equal energy. Therefore, they are more
      likely to migrate out of the laser beam center, weakening the solution's
      absorption that we detect in the Z-scan measurements. Furthermore, we
      theoretically infer that the 19 ps pulse-induced solute migration tends to be
      nonquasistatic and experimentally verify that it cannot be attributed to the
      Soret effect, a quasistatic process.

PMID- 19154043
TI  - Ion-size effect at the surface of a silica hydrosol.
AB  - Using synchrotron x-ray reflectivity, I studied the ion-size effect for alkali
      ions (Na(+), K(+), Rb(+), and Cs(+)), with densities as high as 4x10(18)-7x10(18)
      m(-2), suspended above the surface of a colloidal solution of silica
      nanoparticles in the field generated by the surface electric-double layer. I
      found that large alkali ions preferentially accumulate and replace smaller ones
      at the surface of the hydrosol, a result qualitatively agreeing with the
      dependence of the Kharkats-Ulstrup single-ion electrostatic free energy on the
      ion's radius.

PMID- 19154044
TI  - Structural and electronic properties of identical-sized Zn nanoclusters grown on
      Si(111)-(7x7) surfaces.
AB  - Identical-sized Zn nanoclusters have been grown on Si(111)-(7x7) surfaces at room
      temperature. In situ scanning tunneling microscopy (STM) studies and first
      principles total energy calculations show that room-temperature grown Zn
      nanoclusters tend to form the seven-Zn-atom structure with one excess Zn atom
      occupying characteristically the center of the cluster. The evolution of the
      surface electronic structures measured by scanning tunneling spectroscopy reveals
      that the formation of Zn nanoclusters is responsible for the saturation of the
      metallic Si adatom dangling bond states at about -0.3 and +0.5 V and causes the
      semiconducting characteristics of the nanoclusters. Furthermore, the Zn
      nanocluster in a faulted half unit cell empties the filled surface dangling bond
      state of the closest edge Si adatoms in the nearest neighboring uncovered
      unfaulted half unit cells at about -0.3 V, leading to the suppressed height of
      the closest edge Si adatoms in the filled-state STM images.

PMID- 19154045
TI  - Understanding rubber friction in the presence of water using sum-frequency
      generation spectroscopy.
AB  - Infrared-visible sum-frequency-generation spectroscopy (SFG) was used to study
      the molecular structure of water between a poly(dimethylsiloxane) (PDMS) and a
      sapphire substrate. The observation of SFG peaks associated with the dangling
      surface hydroxyl groups (3690 cm(-1)) and water bands (3000-3400 cm(-1))
      indicates that the contact spot between the PDMS lens and the sapphire substrate
      is heterogeneous. Within the contact spot there are regions where the methyl
      groups of the PDMS chains are in direct contact with the surface hydroxyl groups
      on the sapphire substrate. In the other regions, a thin water layer is trapped
      between the two surfaces with spectral features that are different from that of
      the unconfined water next to the sapphire or the PDMS surface. The higher
      adhesion and friction values observed in these experiments, compared to those
      expected for a uniform thin layer of water trapped between the PDMS and the
      sapphire substrate, are consistent with the hypothesis that the contact spot is
      heterogeneous. These results have important implications in understanding the
      sliding behavior of wet, deformable hydrophobic materials on hydrophilic
      substrates.

PMID- 19154046
TI  - Curvature dependence of the electrolytic liquid-liquid interfacial tension.
AB  - The interfacial tension of a liquid droplet surrounded by another liquid in the
      presence of microscopic ions is studied as a function of the droplet radius. An
      analytical expression for the interfacial tension is obtained within a linear
      Poisson-Boltzmann theory and compared with numerical results from nonlinear
      Poisson-Boltzmann theory. The excess liquid-liquid interfacial tension with
      respect to the pure salt-free liquid-liquid interfacial tension is found to
      decompose into a curvature-independent part due to short-ranged interfacial
      effects and a curvature-dependent electrostatic contribution. Several curvature
      dependent regimes of different scalings of the electrostatic excess interfacial
      tension are identified. Symmetry relations of the interfacial tension upon
      swapping droplet and bulk liquid are found to hold in the low-curvature limit,
      which, e.g., lead to a sign change of the excess Tolman length. For some systems
      a low-curvature expansion up to the second order turns out to be applicable if
      and only if the droplet size exceeds the Debye screening length in the droplet,
      independent of the Debye length in the bulk.

PMID- 19154047
TI  - Charge transfer rates in organic semiconductors beyond first-order perturbation:
      from weak to strong coupling regimes.
AB  - Semiclassical Marcus electron transfer theory is often employed to investigate
      the charge transport properties of organic semiconductors. However, quite often
      the electronic couplings vary several orders of magnitude in organic crystals,
      which goes beyond the application scope of semiclassical Marcus theory with the
      first-order perturbative nature. In this work, we employ a generalized
      nonadiabatic transition state theory (GNTST) [Zhao et al., J. Phys. Chem. A 110,
      8204 (2004)], which can evaluate the charge transfer rates from weak to strong
      couplings, to study charge transport properties in prototypical organic
      semiconductors: quaterthiophene and sexithiophene single crystals. By comparing
      with GNTST results, we find that the semiclassical Marcus theory is valid for the
      case of the coupling <10 meV for quaterthiophene and <5 meV for sexithiophene. It
      is shown that the present approach can be applied to design organic
      semiconductors with general electronic coupling terms. Taking oligothiophenes as
      examples, we find that our GNTST-calculated hole mobility is about three times as
      large as that from the semiclassical Marcus theory. The difference arises from
      the quantum nuclear tunneling and the nonperturbative effects.

PMID- 19154048
TI  - Adenine monolayers on the Au(111) surface: structure identification by scanning
      tunneling microscopy experiment and ab initio calculations.
AB  - From an interplay between scanning tunneling microscopy (STM) and ab initio
      density functional theory (DFT) we have identified and characterized two
      different self-assembled adenine (A) structures formed on the Au(111) surface.
      The STM observations reveal that both structures have a hexagonal geometry in
      which each molecule forms double hydrogen bonds with three nearest neighbors. One
      of the A structures, with four molecules in the primitive cell, has p2gg space
      group symmetry, while the other one, with two molecules in the cell, has p2
      symmetry. The first structure is observed more frequently and is found to be the
      dominating structure after annealing. Experimental as well as theoretical
      findings indicate that the interaction of A molecules with the gold surface is
      rather weak and smooth across the surface. This enabled us to unequivocally
      characterize the observed structures, systematically predict all structural
      possibilities, based on all known A-A dimers, and provisionally optimize
      positions of the A molecules in the cell prior to full-scale DFT calculations.
      The theoretical method is a considerable improvement compared to the approach
      suggested previously by Kelly and Kantorovich [Surf. Sci. 589, 139 (2005)]. We
      propose that the less ordered p2gg symmetry structure is observed more frequently
      due to kinetic effects during island formation upon deposition at room
      temperature.

PMID- 19154049
TI  - Theory of antibunching of photon emission I.
AB  - The photon emission statistics from a single molecule containing
      multichromophores under pulsed excitation is theoretically studied. Fast
      nonradiative pair annihilation of excitons efficiently produces a single exciton,
      which acts as a single photon emitter. By taking into account the discrete nature
      of exciton numbers and the competition among pair annihilation, and unimolecular
      radiative and nonradiative decay of excitons, we obtain analytical expressions of
      photon emission statistics, the average number of emitted photons, and the
      normalized photon pair correlation which represents the ratio of the number of
      photon pairs created by the same pulse to that created by different pulses. The
      normalized photon pair correlation is influenced by the ratio of the pair
      annihilation rate to the total unimolecular decay rate including both radiative
      and nonradiative processes but is not influenced by the ratio of the unimolecular
      radiative and nonradiative rates. On the other hand, the single photon emission
      intensity depends on the ratio of the unimolecular radiative and nonradiative
      rates from the exciton left alone after pair annihilation. The conclusion is
      consistent with recent experimental results on conjugated polymers with various
      sizes in different host materials.

PMID- 19154050
TI  - The driving force of channel formation in triheteropolymers confined in
      nanocylindrical tubes.
AB  - The driving force for channel formation by triheteropolymers confined in
      hydrophobic nanocylinders was investigated by lattice Monte Carlo simulations. A
      variety of conditions, such as the interactions between different kinds of
      segments, the interactions between segments and the nanocylindrical walls, and
      the structure of the polymer, were considered. It was found that for a channel to
      be generated, the attractive interaction between one kind of segments and the
      nanocylindrical wall should be larger than a minimum value. The cross-sectional
      radius of a channel seen from above or below the ends of the nanotube as a
      function of the interactions between the segments and the wall as well as of the
      interactions between different kinds of segments was determined. The succession
      in the chain of different kinds of segments (the chain connectivity) also plays a
      significant role in channel formation. The present treatment may provide some
      insight regarding the formation of protein channels in the phospholipid bilayers
      of the cell membrane.

PMID- 19154051
TI  - Bifurcations in spiral tip dynamics induced by natural convection in the Belousov
      Zhabotinsky reaction.
AB  - The transition to spatial-temporal complexity exhibited by spiral waves under the
      effect of gravitational field in the Belousov-Zhabotinsky reaction is numerically
      studied on the basis of spiral tip dynamics. Successive transformations in tip
      trajectories are characterized as a function of the hydrodynamical parameter and
      attributed to a Ruelle-Takens-Newhouse scenario to chaos. The analysis describes
      the emergence of complexity in terms of the interplay between the evolution of
      the velocity field and concentration waves. In particular, (i) by mapping the tip
      motion in relation to some hydrodynamical pseudopotentials, the general mechanism
      by which the velocity field affects the tip trajectory is pointed out, and, (ii)
      by comparing the dynamical evolutions of local and mean properties associated
      with the inhomogeneous structures and to the velocity field, a surprising
      correlation is found. The results suggest that the reaction-diffusion-convection
      (RDC) coupling addresses the system to some general regimes, whose nature is
      imposed by the hydrodynamical contribution. More generally, RDC coupling would be
      formalized as the phenomenon that governs the system and drives it to chaos.

PMID- 19154052
TI  - Cole-Davidson dynamics of simple chain models.
AB  - Rotational relaxation functions of the end-to-end vector of short, freely jointed
      and freely rotating chains were determined from molecular dynamics simulations.
      The associated response functions were obtained from the one-sided Fourier
      transform of the relaxation functions. The Cole-Davidson function was used to fit
      the response functions with extensive use being made of Cole-Cole plots in the
      fitting procedure. For the systems studied, the Cole-Davidson function provided
      remarkably accurate fits [as compared to the transform of the Kohlrausch-Williams
      Watts (KWW) function]. The only appreciable deviations from the simulation
      results were in the high frequency limit and were due to ballistic or free
      rotation effects. The accuracy of the Cole-Davidson function appears to be the
      result of the transition in the time domain from stretched exponential behavior
      at intermediate time to single exponential behavior at long time. Such a
      transition can be explained in terms of a distribution of relaxation times with a
      well-defined longest relaxation time. Since the Cole-Davidson distribution has a
      sharp cutoff in relaxation time (while the KWW function does not), it makes sense
      that the Cole-Davidson would provide a better frequency-domain description of the
      associated response function than the KWW function does.

PMID- 19154053
TI  - Phase behavior of polyelectrolyte solutions with salt.
AB  - We have computed the phase diagrams of solutions of flexible polyelectrolyte
      chains with added simple electrolytes. The calculations are based on our recent
      theory [M. Muthukumar, Macromolecules 35, 9142 (2002)], which accounts for
      conformational fluctuations of chains, charge density correlations arising from
      dissolved ions, hydrophobic interaction between polymer backbone and solvent, and
      translational entropy of all species in the system. The theory is at the mean
      field level and recovers the results of the restricted primitive model with the
      Debye-Huckel description for solutions of simple electrolytes without any polymer
      chains and those of the Flory-Huggins and scaling theories for uncharged polymers
      in the absence of charges or electrolytes. In constructing the phase diagrams,
      the chemical potential of each of the species is maintained to be the same in the
      coexisting phases and at the same time each phase being electrically neutral
      (Donnan equilibrium). Comparisons are made with a more constrained situation
      where the chemical potentials of the independent components are maintained to be
      the same in the coexisting phases. Our calculations predict several rich
      phenomena. Even for the salt-free solutions, two critical phenomena
      (corresponding to the Flory-Huggins-type and the restricted-primitive-model-type
      critical points) are predicted. The coupling between these two leads to two
      critical end points and triple points. In the presence of salt, the valency of
      electrolyte ions is found to influence drastically the phase diagrams.
      Specifically, the predicted liquid-liquid phase transitions in certain
      temperature ranges is reminiscent of the re-entrant-precipitation phenomenon
      observed experimentally for polyelectrolytes condensed with trivalent salts.

PMID- 19154054
TI  - Methane-water clusters under pressure: are clathrate cages optimal clusters?
AB  - Global cluster structure optimization is applied to CH(4)(H(2)O)(n), n=4-21, in a
      simple model but with the additional application of external pressure. The
      combined effect of pressure and of the presence of a methane molecule leads to a
      structural transition away from the well-known pure water cluster structures. The
      exact location of this transition is a function of pressure and of cluster size,
      but it invariably leads to "nestlike" structures as high-pressure form.
      Clathratelike cages around the methane molecule in the cluster center are less
      favorable than the best nests for all sizes and at all pressures studied, but
      they do become low-energy local minima at high pressures.

PMID- 19154055
TI  - Kinetic models for the coordinated stepping of cytoplasmic dynein.
AB  - To generate processive motion along a polymer track requires that motor proteins
      couple their ATP hydrolysis cycle with conformational changes in their structural
      subunits. Numerous experimental and theoretical efforts have been devoted to
      establishing how this chemomechanical coupling occurs. However, most processive
      motors function as dimers. Therefore a full understanding of the motor's
      performance also requires knowledge of the coordination between the
      chemomechanical cycles of the two heads. We consider a general two-headed model
      for cytoplasmic dynein that is built from experimental measurements on the
      chemomechanical states of monomeric dynein. We explore different possible
      scenarios of coordination that simultaneously satisfy two main requirements of
      the dimeric protein: high processivity (long run length) and high motor velocity
      (fast ATP turnover). To demonstrate the interplay between these requirements and
      the necessity for coordination, we first develop and analyze a simple mechanical
      model for the force-induced stepping in the absence of ATP. Next we use a
      simplified model of dimeric dynein's chemomechanical cycle to establish the
      kinetic rules that must be satisfied for the model to be consistent with recent
      data for the motor's performance from single molecule experiments. Finally, we
      use the results of these investigations to develop a full model for dimeric
      dynein's chemomechanical cycle and analyze this model to make experimentally
      testable predictions.

PMID- 19154056
TI  - Direct evidence for mode-specific vibrational energy relaxation from quantum time
      dependent perturbation theory. I. Five-coordinate ferrous iron porphyrin model.
AB  - The time scales and mechanisms of mode-specific vibrational energy relaxation in
      imidazole ligated ferrous iron porphine were studied using a non-Markovian time
      dependent perturbation theory and density functional theory calculation. Seven
      normal modes, including nu(4), nu(7), and five Fe out-of-plane modes (Fe-oop),
      were treated as the relaxing system mode coupled to all other modes forming the
      bath. The derived cooling time constants for the nu(4) and nu(7) modes agree well
      with the results of previous experimental studies. The pathways for energy
      transfer from each system mode were identified. The gamma(7) mode, associated
      with Fe-oop motion with frequency approximately 350 cm(-1), was observed to
      couple strongly through its overtone with the nu(7) porphine in-plane vibration.
      This suggests a possible mechanism for the excitation of the nu(7) mode, which is
      distinct from the direct excitation together with Fe-oop motion of the nu(4)
      mode. Four other Fe-oop motions were observed to couple to low frequency modes
      including those involving significant imidazole ligand motions. Through these
      couplings, excitation following ligand photodissociation may be efficiently
      transferred from the heme doming mode to the protein backbone motions essential
      to conformational changes associated with the protein's function.

PMID- 19154057
TI  - Single polymer confinement in a tube: correlation between structure and dynamics.
AB  - In this paper, we construct an effective model for the dynamics of an excluded
      volume chain under confinement by extending the formalism of Rouse modes. We make
      specific predictions about the behavior of the modes for a single polymer
      confined to a tube. The results are tested against Monte Carlo simulations using
      the bond-fluctuation algorithm which uses a lattice representation of the polymer
      chain with excluded-volume effects.

PMID- 19154060
TI  - Abdominal aortic aneurysm risk of rupture: patient-specific FSI simulations using
      anisotropic model.
AB  - Abdominal aortic aneurysm (AAA) rupture represents a major cardiovascular risk,
      combining complex vascular mechanisms weakening the abdominal artery wall coupled
      with hemodynamic forces exerted on the arterial wall. At present, a reliable
      method to predict AAA rupture is not available. Recent studies have introduced
      fluid structure interaction (FSI) simulations using isotropic wall properties to
      map regions of stress concentrations developing in the aneurismal wall as a much
      better alternative to the current clinical criterion, which is based on the AAA
      diameter alone. A new anisotropic material model of AAA that closely matches
      observed biomechanical AAA material properties was applied to FSI simulations of
      patient-specific AAA geometries in order to develop a more reliable predictor for
      its risk of rupture. Each patient-specific geometry was studied with and without
      an intraluminal thrombus (ILT) using two material models-the more commonly used
      isotropic material model and an anisotropic material model-to delineate the ILT
      contribution and the dependence of stress distribution developing within the
      aneurismal wall on the material model employed. Our results clearly indicate
      larger stress values for the anisotropic material model and a broader range of
      stress values as compared to the isotropic material, indicating that the latter
      may underestimate the risk of rupture. While the locations of high and low
      stresses are consistent in both material models, the differences between the
      anisotropic and isotropic models become pronounced at large values of strain-a
      range that becomes critical when the AAA risk of rupture is imminent. As the
      anisotropic model more closely matches the biomechanical behavior of the AAA wall
      and resolves directional strength ambiguities, we conclude that it offers a more
      reliable predictor of AAA risk of rupture.

PMID- 19154061
TI  - Two-dimensional simulation of flow and platelet dynamics in the hinge region of a
      mechanical heart valve.
AB  - The hinge region of a mechanical bileaflet valve is implicated in blood damage
      and initiation of thrombus formation. Detailed fluid dynamic analysis in the
      complex geometry of the hinge region during the closing phase of the bileaflet
      valve is the focus of this study to understand the effect of fluid-induced
      stresses on the activation of platelets. A fixed-grid Cartesian mesh flow solver
      is used to simulate the blood flow through a two-dimensional geometry of the
      hinge region of a bileaflet mechanical valve. Use of local mesh refinement
      algorithm provides mesh adaptation based on the gradients of flow in the
      constricted geometry of the hinge. Leaflet motion is specified from the fluid
      structure interaction analysis of the leaflet dynamics during the closing phase
      from a previous study, which focused on the fluid mechanics at the gap between
      the leaflet edges and the valve housing. A Lagrangian particle tracking method is
      used to model and track the platelets and to compute the magnitude of the shear
      stress on the platelets as they pass through the hinge region. Results show that
      there is a boundary layer separation in the gaps between the leaflet ear and the
      constricted hinge geometry. Separated shear layers roll up into vortical
      structures that lead to high residence times combined with exposure to high-shear
      stresses for particles in the hinge region. Particles are preferentially
      entrained into this recirculation zone, presenting the possibility of platelet
      activation, aggregation, and initiation of thrombi.

PMID- 19154062
TI  - A low-dimensional sagittal-plane forward-dynamic model for asymmetric gait and
      its application to study the gait of transtibial prosthesis users.
AB  - This paper presents an extension of a recently developed low-dimensional modeling
      approach for normal human gait to the modeling of asymmetric gait. The asymmetric
      model is applied to analyze the gait dynamics of a transtibial prosthesis user,
      specifically the changes in joint torque and joint power costs that occur with
      variations in sagittal-plane alignment of the prosthesis, mass distribution of
      the prosthesis, and roll-over shape of the prosthetic foot being used. The model
      predicts an increase in cost with addition of mass and a more distal location of
      the mass, as well as the existence of an alignment at which the costs are
      minimized. The model's predictions also suggest guidelines for the selection of
      prosthetic feet and suitable alignments. The results agree with clinical
      observations and results of other gait studies reported in the literature. The
      model can be a useful analytical tool for more informed design and selection of
      prosthetic components, and provides a basis for making the alignment process
      systematic.

PMID- 19154063
TI  - Fibril microstructure affects strain transmission within collagen extracellular
      matrices.
AB  - The next generation of medical devices and engineered tissues will require
      development of scaffolds that mimic the structural and functional properties of
      the extracellular matrix (ECM) component of tissues. Unfortunately, little is
      known regarding how ECM microstructure participates in the transmission of
      mechanical load information from a global (tissue or construct) level to a level
      local to the resident cells ultimately initiating relevant mechanotransduction
      pathways. In this study, the transmission of mechanical strains at various
      functional levels was determined for three-dimensional (3D) collagen ECMs that
      differed in fibril microstructure. Microstructural properties of collagen ECMs
      (e.g., fibril density, fibril length, and fibril diameter) were systematically
      varied by altering in vitro polymerization conditions. Multiscale images of the
      3D ECM macro- and microstructure were acquired during uniaxial tensile loading.
      These images provided the basis for quantification and correlation of strains at
      global and local levels. Results showed that collagen fibril microstructure was a
      critical determinant of the 3D global and local strain behaviors. Specifically,
      an increase in collagen fibril density reduced transverse strains in both width
      and thickness directions at both global and local levels. Similarly, collagen
      ECMs characterized by increased fibril length and decreased fibril diameter
      exhibited increased strain in width and thickness directions in response to
      loading. While extensional strains measured globally were equivalent to applied
      strains, extensional strains measured locally consistently underpredicted applied
      strain levels. These studies demonstrate that regulation of collagen fibril
      microstructure provides a means to control the 3D strain response and strain
      transfer properties of collagen-based ECMs.

PMID- 19154064
TI  - Optimal estimation of dynamically consistent kinematics and kinetics for forward
      dynamic simulation of gait.
AB  - Forward dynamic simulation provides a powerful framework for characterizing
      internal loads and for predicting changes in movement due to injury, impairment
      or surgical intervention. However, the computational challenge of generating
      simulations has greatly limited the use and application of forward dynamic models
      for simulating human gait. In this study, we introduce an optimal estimation
      approach to efficiently solve for generalized accelerations that satisfy the
      overall equations of motion and best agree with measured kinematics and ground
      reaction forces. The estimated accelerations are numerically integrated to
      enforce dynamic consistency over time, resulting in a forward dynamic simulation.
      Numerical optimization is then used to determine a set of initial generalized
      coordinates and speeds that produce a simulation that is most consistent with the
      measured motion over a full cycle of gait. The proposed method was evaluated with
      synthetically created kinematics and force plate data in which both random noise
      and bias errors were introduced. We also applied the method to experimental gait
      data collected from five young healthy adults walking at a preferred speed. We
      show that the proposed residual elimination algorithm (REA) converges to an
      accurate solution, reduces the detrimental effects of kinematic measurement
      errors on joint moments, and eliminates the need for residual forces that arise
      in standard inverse dynamics. The greatest improvements in joint kinetics were
      observed proximally, with the algorithm reducing joint moment errors due to
      marker noise by over 20% at the hip and over 50% at the low back. Simulated joint
      angles were generally within 1 deg of recorded values when REA was used to
      generate a simulation from experimental gait data. REA can thus be used as a
      basis for generating accurate simulations of subject-specific gait dynamics.

PMID- 19154065
TI  - Spatially resolved streaming potentials of human intervertebral disk motion
      segments under dynamic axial compression.
AB  - Intervertebral disk degeneration results in alterations in the mechanical,
      chemical, and electrical properties of the disk tissue. The purpose of this study
      is to record spatially resolved streaming potential measurements across
      intervertebral disks exposed to cyclic compressive loading. We hypothesize that
      the streaming potential profile across the disk will vary with radial position
      and frequency and is proportional to applied load amplitude, according to the
      presumed fluid-solid relative velocity and measured glycosaminoglycan content.
      Needle electrodes were fabricated using a linear array of AgAgCl micro-electrodes
      and inserted into human motion segments in the midline from anterior to
      posterior. They were connected to an amplifier to measure electrode potentials
      relative to the saline bath ground. Motion segments were loaded in axial
      compression under a preload of 500 N, sinusoidal amplitudes of +/-200 N and +/
      400 N, and frequencies of 0.01 Hz, 0.1 Hz, and 1 Hz. Streaming potential data
      were normalized by applied force amplitude, and also compared with paired
      experimental measurements of glycosaminoglycans in each disk. Normalized
      streaming potentials varied significantly with sagittal position and there was a
      significant location difference at the different frequencies. Normalized
      streaming potential was largest in the central nucleus region at frequencies of
      0.1 Hz and 1.0 Hz with values of approximately 3.5 microVN. Under 0.01 Hz
      loading, normalized streaming potential was largest in the outer annulus regions
      with a maximum value of 3.0 microVN. Correlations between streaming potential and
      glycosaminoglycan content were significant, with R(2) ranging from 0.5 to 0.8.
      Phasic relationships between applied force and electrical potential did not
      differ significantly by disk region or frequency, although the largest phase
      angles were observed at the outermost electrodes. Normalized streaming potentials
      were associated with glycosaminoglycan content, fluid, and ion transport. Results
      suggested that at higher frequencies the transport of water and ions in the
      central nucleus region may be larger, while at lower frequencies there is
      enhanced transport near the periphery of the annulus. This study provides data
      that will be helpful to validate multiphasic models of the disk.

PMID- 19154066
TI  - Material properties of the axillary pouch of the glenohumeral capsule: is
      isotropic material symmetry appropriate?
AB  - Inconclusive findings regarding the collagen fiber architecture and the material
      properties of the glenohumeral capsule make it unclear whether the material
      symmetry of the glenohumeral capsule is isotropic or anisotropic. The overall
      objective of this work was to use a combined experimental and computational
      protocol to characterize the mechanical properties of the axillary pouch of the
      glenohumeral capsule and to determine the appropriate material symmetry. Two
      perpendicular tensile and finite simple shear deformations were applied to a
      series of tissue samples from the axillary pouch of the glenohumeral capsule. An
      inverse finite element optimization routine was then used to determine the
      material coefficients for an isotropic hyperelastic constitutive model by
      simulating the experimental conditions. There were no significant differences
      between the material coefficients obtained from the two perpendicular tensile
      deformations or finite simple shear deformations. Furthermore, stress-stretch
      relationships predicted by utilizing the material coefficients from one direction
      were able to predict the responses of the same tissue sample in the perpendicular
      direction. These similarities between the longitudinal and transverse material
      behaviors of the tissue imply that the capsule may be considered an isotropic
      material. However, differences did exist between the material coefficients
      obtained from the tensile and shear loading conditions. Therefore, a more
      advanced constitutive model is needed to predict both the tensile and shear
      responses of the material.

PMID- 19154067
TI  - Cartilage collagen matrix reorientation and displacement in response to surface
      loading.
AB  - An investigation of collagen fiber reorientation, as well as fluid and matrix
      movement of equine articular cartilage and subchondral bone under compressive
      mechanical loads, was undertaken using small angle X-ray scattering measurements
      and optical microscopy. Small angle X-ray scattering measurements were made on
      healthy and diseased samples of equine articular cartilage and subchondral bone
      mounted in a mechanical testing apparatus on station ID18F of ESRF, Grenoble,
      together with fiber orientation analysis using polarized light and displacement
      measurements of the cartilage matrix and fluid using tracers. At surface
      pressures of up to approximately 1.5 MPa, there was reversible compression of the
      tangential surface fibers and immediately subjacent zone. As load increased,
      deformation in these zones reached a maximum and then reorientation propagated to
      the radial deep zone. Between surface pressures of 4.8 MPa and 6.0 MPa, fiber
      orientation above the tide mark rotated 10 deg from the radial direction, with an
      overall loss of alignment. With further increase in load, the fibers "crimped" as
      shown by the appearance of subsidiary peaks approximately +/-10 deg either side
      of the principal fiber orientation direction. Failure at higher loads was
      characterized by a radial split in the deep cartilage, which propagated along the
      tide mark while the surface zone remained intact. In lesions, the fiber
      organization was disrupted and the initial response to load was consistent with
      early rupture of fibers, but the matrix relaxed to an organization very similar
      to that of the unloaded tissue. Tracer measurements revealed anisotropic solid
      and fluid displacement, which depended strongly on depth within the tissue.

PMID- 19154068
TI  - Viscoelasticity and preconditioning of rat skin under uniaxial stretch:
      microstructural constitutive characterization.
AB  - In spite of impressive progress in developing general constitutive laws for soft
      tissues, there exists still no comprehensive model valid for any general
      deformation scheme. The present study focuses on the uniaxial response of the
      skin as a model for other multifibrous soft tissues. While the skin's nonlinear
      viscoelastic constitutive response has been extensively studied and modeled, the
      phenomena associated with mechanical preconditioning have so far not been dealt
      with. Yet preconditioning is an inherent response feature in the skin, both in
      vitro and in vivo. It is hypothesized that by considering the structure of the
      elastic and collagen fibers and their individual rheological properties, it is
      possible to develop a reliable general constitutive law for the skin's uniaxial
      response. A stochastic hybrid constitutive model was developed based on the
      collagen and elastic fiber morphologies and their rheological properties. The
      multiple protocol uniaxial data of Eshel and Lanir ("Effects of Strain Level and
      Proteoglycan Depletion on Preconditioning and Viscoelastic Responses of Rat
      Dorsal Skin," 2001, Ann. Biomed. Eng., 29, pp. 164-172) served to estimate the
      model's parameters and to validate its reliability. Parametric investigation was
      then used to test model parsimony (minimal form) and to elucidate the roles of
      response mechanism and the relative contribution of each constituent. The model
      predictions show a very close fit to the data and good predictive capability. The
      results are consistent with the quasilinear viscoelastic response of both elastic
      and collagen fibers and are likewise consistent with the notion (supported by
      published experimental observations) that preconditioning in collagen is probably
      due to an increase in the fiber reference length and is due to strain softening
      (Mullins effect) in elastic fibers. The predictions also agree with the observed
      predominance of elastic fibers at low strains and suggest that as strain
      increases, collagen becomes predominant, but the effect of elastic fibers is
      still significant. The parsimony analysis of the 22 model parameters (18 are
      nonlinear in the model) points to the predominant role of viscoelasticity and
      preconditioning in both fibers, followed in order of importance by collagen
      waviness and elastic fiber nonlinearity. A reliable and comprehensive uniaxial
      constitutive law for the rat skin was developed based on the tissue
      microstructure and on its constituents' rheological properties.

PMID- 19154069
TI  - Respiratory flow phenomena and gravitational deposition in a three-dimensional
      space-filling model of the pulmonary acinar tree.
AB  - The inhalation of micron-sized aerosols into the lung's acinar region may be
      recognized as a possible health risk or a therapeutic tool. In an effort to
      develop a deeper understanding of the mechanisms responsible for acinar
      deposition, we have numerically simulated the transport of nondiffusing fine
      inhaled particles (1 mum and 3 microm in diameter) in two acinar models of
      varying complexity: (i) a simple alveolated duct and (ii) a space-filling
      asymmetrical acinar branching tree following the description of lung structure by
      Fung (1988, "A Model of the Lung Structure and Its Validation," J. Appl.
      Physiol., 64, pp. 2132-2141). Detailed particle trajectories and deposition
      efficiencies, as well as acinar flow structures, were investigated under
      different orientations of gravity, for tidal breathing motion in an average human
      adult. Trajectories and deposition efficiencies inside the alveolated duct are
      strongly related to gravity orientation. While the motion of larger particles (3
      microm) is relatively insensitive to convective flows compared with the role of
      gravitational sedimentation, finer 1 microm aerosols may exhibit, in contrast,
      complex kinematics influenced by the coupling between (i) flow reversal due to
      oscillatory breathing, (ii) local alveolar flow structure, and (iii) streamline
      crossing due to gravity. These combined mechanisms may lead to twisting and
      undulating trajectories in the alveolus over multiple breathing cycles. The
      extension of our study to a space-filling acinar tree was well suited to
      investigate the influence of bulk kinematic interaction on aerosol transport
      between ductal and alveolar flows. We found the existence of intricate
      trajectories of fine 1 microm aerosols spanning over the entire acinar airway
      network, which cannot be captured by simple alveolar models. In contrast, heavier
      3 microm aerosols yield trajectories characteristic of gravitational
      sedimentation, analogous to those observed in the simple alveolated duct. For
      both particle sizes, however, particle inhalation yields highly nonuniform
      deposition. While larger particles deposit within a single inhalation phase,
      finer 1 microm particles exhibit much longer residence times spanning multiple
      breathing cycles. With the ongoing development of more realistic models of the
      pulmonary acinus, we aim to capture some of the complex mechanisms leading to
      deposition of inhaled aerosols. Such models may lead to a better understanding
      toward the optimization of pulmonary drug delivery to target specific regions of
      the lung.

PMID- 19154070
TI  - A model of the upper extremity using FES for stroke rehabilitation.
AB  - A model of the upper extremity is developed in which the forearm is constrained
      to lie in a horizontal plane and electrical stimulation is applied to the triceps
      muscle. Identification procedures are described to estimate the unknown
      parameters using tests that can be performed in a short period of time. Examples
      of identified parameters obtained experimentally are presented for both stroke
      patients and unimpaired subjects. A discussion concerning the identification's
      repeatability, together with results confirming the accuracy of the overall
      representation, is given. The model has been used during clinical trials in which
      electrical stimulation is applied to the triceps muscle of a number of stroke
      patients for the purpose of improving both their performance at reaching tasks
      and their level of voluntary control over their impaired arm. Its purpose in this
      context is threefold: Firstly, changes occurring in the levels of stiffness and
      spasticity in each subject's arm can be monitored by comparing frictional
      components of models identified at different times during treatment. Secondly,
      the model is used to calculate the moments applied during tracking tasks that are
      due to a patient's voluntary effort, and it therefore constitutes a useful tool
      with which to analyze their performance. Thirdly, the model is used to derive the
      advanced controllers that govern the level of stimulation applied to subjects
      over the course of the treatment. Details are provided to show how the model is
      applied in each case, and sample results are shown.

PMID- 19154071
TI  - Effects of dressing type on 3D tissue microdeformations during negative pressure
      wound therapy: a computational study.
AB  - Vacuum-assisted closure (VAC) therapy, also referred to as vacuum-assisted
      closure negative pressure wound therapy (VAC NPWT), delivered to various dermal
      wounds is believed to influence the formation of granulation tissue via the
      mechanism of microdeformational signals. In recent years, numerous experimental
      investigations have been initiated to study the cause-effect relationships
      between the mechanical signals and the transduction pathways that result in
      improved granulation response. To accurately quantify the tissue
      microdeformations during therapy, a new three-dimensional finite element model
      has been developed and is described in this paper. This model is used to study
      the effect of dressing type and subatmospheric pressure level on the variations
      in the microdeformational strain fields in a model dermal wound bed. Three
      dimensional geometric models representing typical control volumes of NPWT
      dressings were generated using micro-CT scanning of VAC GranuFoam, a reticulated
      open-cell polyurethane foam (ROCF), and a gauze dressing (constructed from USP
      Class VII gauze). Using a nonlinear hyperfoam constitutive model for the wound
      bed, simulated tissue microdeformations were generated using the foam and gauze
      dressing models at equivalent negative pressures. The model results showed that
      foam produces significantly greater strain than gauze in the tissue model at all
      pressures and in all metrics (p<0.0001 for all but epsilon(vol) at -50 mm Hg and 
      100 mm Hg where p<0.05). Specifically, it was demonstrated in this current work
      that the ROCF dressing produces higher levels of tissue microdeformation than
      gauze at all levels of subatmospheric pressure. This observation is consistent
      across all of the strain invariants assessed, i.e., epsilon(vol), epsilon(dist),
      the minimum and maximum principal strains, and the maximum shear strain. The
      distribution of the microdeformations and strain appears as a repeating mosaic
      beneath the foam dressing, whereas the gauze dressings appear to produce an
      irregular distribution of strains in the wound surface. Strain predictions from
      the developed computational model results agree well with those predicted from
      prior two-dimensional experimental and computational studies of foam-based NPWT
      (Saxena, V., et al., 2004, "Vacuum-assisted closure: Microdeformations of Wounds
      and Cell Proliferation," Plast. Reconstr. Surg., 114(5), pp. 1086-1096). In
      conjunction with experimental in vitro and in vivo studies, the developed model
      can now be extended into more detailed investigations into the mechanobiological
      underpinnings of VAC NPWT and can help to further develop and optimize this
      treatment modality for the treatment of challenging patient wounds.

PMID- 19154072
TI  - A mechanical model of the human ankle in the transverse plane during straight
      walking: implications for prosthetic design.
AB  - In order to protect sensitive residual limb soft tissues, lower limb prostheses
      need to control torsional loads during gait. To assist with the design of a
      torsional prosthesis, this paper used simple mechanical elements to model the
      behavior of the human ankle in the transverse plane during straight walking.
      Motion capture data were collected from ten able-bodied subjects walking straight
      ahead at self-selected walking speeds. Gait cycle data were separated into four
      distinct states, and passive torsional springs and dampers were chosen to model
      the behavior in each state. Since prosthetic design is facilitated by simplicity,
      it was desirable to investigate if elastic behavior could account for the
      physiological ankle moment and include viscous behavior only if necessary to
      account for the inadequacies of the spring model. In all four states, a
      springlike behavior was able to account for most of the physiological ankle
      moments, rendering the use of a damper unnecessary. In State 1, a quadratic
      torsional spring was chosen to model the behavior, while linear torsional springs
      were chosen for States 2-4. A prosthetic system that actively changes stiffness
      could be able to replicate the physiological behavior of the human ankle in the
      transverse plane. The results of this study will contribute to the mechanical
      design and control of a biomimetic torsional prosthesis for lower limb amputees.

PMID- 19154073
TI  - Can pelvis angle be monitored from seat support forces in healthy subjects?
AB  - Individuals who cannot functionally reposition themselves often need dynamic
      seating interventions that change body posture from automatic chair adjustments.
      Pelvis alignment directly affects sitting posture, and systems that adjust and
      monitor pelvis angle simultaneously might be applicable to control body posture
      in sitting. The present study explores whether it is feasible to monitor pelvis
      angle from seat support forces. Pelvis angle estimation was based on equivalent
      "two-force member" loading for which pelvis orientation equals the orientation of
      the equivalent contact force. Theoretical evaluation was done to derive important
      conditions for practical application. An instrumented wheelchair was developed
      for experimental validation in healthy subjects. Seat support forces were
      measured, and mechanical analysis was done to derive the equivalent contact force
      from which we estimated the pelvis angle. Model analysis showed a significant
      influence of pelvis mass, hip force, and lumbar torque on the relation between
      the actual pelvis angle and the predicted pelvis angle. Proper force compensation
      and minimal lumbar torque seemed important for accurate pelvis angle estimations.
      Experimental evaluation showed no body postures that involved a clear relation
      between the pelvis angle and the orientation of the equivalent contact force.
      Findings suggest that pelvis angle could not be estimated in healthy individuals
      under the described experimental seating conditions. Validation experiments with
      impaired individuals must be performed under different seating conditions to
      provide a better understanding whether the principle is of interest for clinical
      application.

PMID- 19154074
TI  - Effect of calibration method on Tekscan sensor accuracy.
AB  - Tekscan pressure sensors are used in biomechanics research to measure joint
      contact loads. While the overall accuracy of these sensors has been reported
      previously, the effects of different calibration algorithms on sensor accuracy
      have not been compared. The objectives of this validation study were to determine
      the most appropriate calibration method supplied in the Tekscan program software
      and to compare its accuracy to the accuracy obtained with two user-defined
      calibration protocols. We evaluated the calibration accuracies for test loads
      within the low range, high range, and full range of the sensor. Our experimental
      setup used materials representing those found in standard prosthetic joints,
      i.e., metal against plastic. The Tekscan power calibration was the most accurate
      of the algorithms provided with the system software, with an overall rms error of
      2.7% of the tested sensor range, whereas the linear calibrations resulted in an
      overall rms error of up to 24% of the tested range. The user-defined ten-point
      cubic calibration was almost five times more accurate, on average, than the power
      calibration over the full range, with an overall rms error of 0.6% of the tested
      range. The user-defined three-point quadratic calibration was almost twice as
      accurate as the Tekscan power calibration, but was sensitive to the calibration
      loads used. We recommend that investigators design their own calibration curves
      not only to improve accuracy but also to understand the range(s) of highest error
      and to choose the optimal points within the expected sensing range for
      calibration. Since output and sensor nonlinearity depend on the experimental
      protocol (sensor type, interface shape and materials, sensor range in use,
      loading method, etc.), sensor behavior should be investigated for each different
      application.

PMID- 19154075
TI  - Foot segment kinematics during normal walking using a multisegment model of the
      foot and ankle complex.
AB  - Gait analysis using optical tracking equipment has been demonstrated to be a
      clinically useful tool for measuring three-dimensional kinematics and kinetics of
      the human body. However, in current practice, the foot is treated as a single
      rigid segment that articulates with the lower leg, meaning the motions of the
      joints of the foot cannot be measured. A multisegment kinematic model of the foot
      was developed for use in a gait analysis laboratory. The foot was divided into
      hindfoot, talus, midfoot, and medial and lateral forefoot segments. Six
      functional joints were defined: Ankle and subtalar joints, frontal and transverse
      plane motions of the hindfoot relative to midfoot, supination-pronation twist of
      the forefoot relative to midfoot, and medial longitudinal arch height-to-length
      ratio. Twelve asymptomatic subjects were tested during barefoot walking with a
      six-camera optical stereometric system and passive markers organized in triads.
      Repeatability of reported motions was tested using coefficients of multiple
      correlation. Ankle and subtalar joint motions and twisting of the forefoot were
      most repeatable. Hindfoot motions were least repeatable both within subjects and
      between subjects. Hindfoot and forefoot pronations in the frontal place were
      found to coincide with dropping of the medial longitudinal arch between early to
      midstance, followed by supination and rising of the arch in late stance and swing
      phase. This multisegment foot model overcomes a major shortcoming in current gait
      analysis practice-the inability to measure motion within the foot. Such
      measurements are crucial if gait analysis is to remain relevant in orthopaedic
      and rehabilitative treatment of the foot and ankle.

PMID- 19154076
TI  - Design and evaluation of a new general-purpose device for calibrating
      instrumented spatial linkages.
AB  - Because instrumented spatial linkages (ISLs) have been commonly used in measuring
      joint rotations and must be calibrated before using the device in confidence, a
      calibration device design and associated method for quantifying calibration
      device error would be useful. The objectives of the work reported by this paper
      were to (1) design an ISL calibration device and demonstrate the design for a
      specific application, (2) describe a new method for calibrating the device that
      minimizes measurement error, and (3) quantify measurement error of the device
      using the new method. Relative translations and orientations of the device were
      calculated via a series of transformation matrices containing inherent fixed and
      variable parameters. These translations and orientations were verified with a
      coordinate measurement machine, which served as a gold standard. Inherent fixed
      parameters of the device were optimized to minimize measurement error. After
      parameter optimization, accuracy was determined. The root mean squared error
      (RMSE) was 0.175 deg for orientation and 0.587 mm for position. All RMSE values
      were less than 0.8% of their respective full-scale ranges. These errors are
      comparable to published measurement errors of ISLs for positions and lower by at
      least a factor of 2 for orientations. These errors are in spite of the many steps
      taken in design and manufacturing to achieve high accuracy. Because it is
      challenging to achieve the accuracy required for a custom calibration device to
      serve as a viable gold standard, it is important to verify that a calibration
      device provides sufficient precision to calibrate an ISL.

PMID- 19154077
TI  - Correlation between angiographic and particle image velocimetry quantifications
      of flow diverters in an in vitro model of elastase-induced rabbit aneurysms.
AB  - The rupture of a cerebral aneurysm can result in a hemorrhagic stroke. A flow
      diverter, which is a porous tubular mesh, can be placed across the neck of a
      cerebral aneurysm to induce the cessation of flow and initiate the formation of
      an intra-aneurysmal thrombus. By finding a correlation between particle image
      velocimetry (PIV) and digital subtraction angiography, a better assessment of how
      well an aneurysm is excluded from the parent artery can be made in the clinical
      setting. A model of a rabbit elastase-induced aneurysm was connected to a mock
      circulation loop. The model was then placed under angiography. Recorded
      angiograms were analyzed so that a contrast concentration-time curve based on the
      average grayscale intensity inside the aneurysm could be determined. That curve
      was then fitted to a mathematical model that quantifies the influence of
      convection and diffusion on contrast transport. Optimized parameters were
      correlated with the intraneurysmal mean kinetic energy measured by PIV in the
      same aneurysm model. A strong correlation was observed between the convection and
      diffusion time constants and the mean kinetic energy inside the aneurysm.
      Analyzing the flow of angiographic contrast into and out of the aneurysm after
      implantation of a flow diverter allows for prediction of the efficacy of the
      device in excluding the aneurysm. Correlating hydrodynamic measures obtained by
      angiography to those obtained by detailed techniques such as PIV increases
      confidence in such predictions.

PMID- 19154078
TI  - Development of a three-dimensional bioprinter: construction of cell supporting
      structures using hydrogel and state-of-the-art inkjet technology.
AB  - We have developed a new technology for producing three-dimensional (3D)
      biological structures composed of living cells and hydrogel in vitro, via the
      direct and accurate printing of cells with an inkjet printing system. Various
      hydrogel structures were constructed with our custom-made inkjet printer, which
      we termed 3D bioprinter. In the present study, we used an alginate hydrogel that
      was obtained through the reaction of a sodium alginate solution with a calcium
      chloride solution. For the construction of the gel structure, sodium alginate
      solution was ejected from the inkjet nozzle (SEA-Jet, Seiko Epson Corp., Suwa,
      Japan) and was mixed with a substrate composed of a calcium chloride solution. In
      our 3D bioprinter, the nozzle head can be moved in three dimensions. Owing to the
      development of the 3D bioprinter, an innovative fabrication method that enables
      the gentle and precise fixation of 3D gel structures was established using living
      cells as a material. To date, several 3D structures that include living cells
      have been fabricated, including lines, planes, laminated structures, and tubes,
      and now, experiments to construct various hydrogel structures are being carried
      out in our laboratory.

PMID- 19154079
TI  - Prosthetic ankle-foot mechanism capable of automatic adaptation to the walking
      surface.
AB  - A conceptual design has been generated for a prosthetic ankle-foot mechanism that
      can automatically adapt to the slope of the walking surface. To help prove this
      concept, a prototype ankle-foot mechanism was designed, developed, and tested on
      three subjects with unilateral transtibial amputations walking on level and
      ramped surfaces. The mechanism is capable of automatically adapting to the
      walking surface by switching impedance modes at key points of the gait cycle. The
      mechanism simulates the behavior of the physiologic foot and ankle complex by
      having a low impedance in the early stance phase and then switching to a higher
      impedance once foot-flat is reached. The "set-point" at which these changes in
      impedance occur gets reset on every step in order to reach the proper alignment
      for the walking surface. The mechanism utilizes the user's bodyweight to help
      switch impedance modes and does not require any active control. It was
      hypothesized that the ankle-foot mechanism would cause the equilibrium point of
      the ankle moment versus the ankle dorsiflexion angle curves to shift to
      accommodate the walking surface. For two of the three subjects tested, this
      behavior was confirmed, supporting the contention that the design provides
      automatic adaptation for different walking slopes. Further work is needed to
      develop the prototype into a commercial product, but the mechanism was sufficient
      for illustrating proof-of-concept.

PMID- 19154080
TI  - Nested uncertainties in biochemical models.
AB  - Dynamic modelling of biochemical reaction networks has to cope with the inherent
      uncertainty about biological processes, concerning not only data and parameters
      but also kinetics and structure. These different types of uncertainty are nested
      within each other: uncertain network structures contain uncertain reaction
      kinetics, which in turn are governed by uncertain parameters. Here, the authors
      review some issues arising from such uncertainties and sketch methods, solutions
      and future directions to deal with them.

PMID- 19154081
TI  - Optimal experimental design with the sigma point method.
AB  - Using mathematical models for a quantitative description of dynamical systems
      requires the identification of uncertain parameters by minimising the difference
      between simulation and measurement. Owing to the measurement noise also, the
      estimated parameters possess an uncertainty expressed by their variances. To
      obtain highly predictive models, very precise parameters are needed. The optimal
      experimental design (OED) as a numerical optimisation method is used to reduce
      the parameter uncertainty by minimising the parameter variances iteratively. A
      frequently applied method to define a cost function for OED is based on the
      inverse of the Fisher information matrix. The application of this traditional
      method has at least two shortcomings for models that are nonlinear in their
      parameters: (i) it gives only a lower bound of the parameter variances and (ii)
      the bias of the estimator is neglected. Here, the authors show that by applying
      the sigma point (SP) method a better approximation of characteristic values of
      the parameter statistics can be obtained, which has a direct benefit on OED. An
      additional advantage of the SP method is that it can also be used to investigate
      the influence of the parameter uncertainties on the simulation results. The SP
      method is demonstrated for the example of a widely used biological model.

PMID- 19154082
TI  - Mixed-integer nonlinear optimisation approach to coarse-graining biochemical
      networks.
AB  - Quantitative modelling and analysis of biochemical networks is challenging
      because of the inherent complexities and nonlinearities of the system and the
      limited availability of parameter values. Even if a mathematical model of the
      network can be developed, the lack of large-scale good-quality data makes
      accurate estimation of a large number of parameters impossible. Hence, coarse
      grained models (CGMs) consisting of essential biochemical mechanisms are more
      suitable for computational analysis and for studying important systemic
      functions. The central question in constructing a CGM is which mechanisms should
      be deemed 'essential' and which can be ignored. Also, how should parameter values
      be defined when data are sparse? A mixed-integer nonlinear-programming (MINLP)
      based optimisation approach to coarse-graining is presented. Starting with a
      detailed biochemical model with associated computational details (reaction
      network and mathematical description) and data on the biochemical system, the
      structure and the parameters of a CGM can be determined simultaneously. In this
      optimisation problem, the authors use a genetic algorithm to simultaneously
      identify parameter values and remove unimportant reactions. The methodology is
      exemplified by developing two CGMs for the GTPase-cycle module of M1 muscarinic
      acetylcholine receptor, Gq, and regulator of G protein signalling 4 [RGS4, a
      GTPase-activating protein (GAP)] starting from a detailed model of 48 reactions.
      Both the CGMs have only 17 reactions, fit experimental data well and predict, as
      does the detailed model, four limiting signalling regimes (LSRs) corresponding to
      the extremes of receptor and GAP concentration. The authors demonstrate that
      coarse-graining, in addition to resulting in a reduced-order model, also provides
      insights into the mechanisms in the network. The best CGM obtained for the GTPase
      cycle also contains an unconventional mechanism and its predictions explain an
      old problem in pharmacology, the biphasic (bell-shaped) response to certain
      drugs. The MINLP methodology is broadly applicable to larger and complex (dense)
      biochemical modules.

PMID- 19154083
TI  - Proper lumping in systems biology models.
AB  - An algorithm for automatic order reduction of models defined by large systems of
      differential equations is presented. The algorithm was developed with systems
      biology models in mind and the motivation behind it is to develop mechanistic
      pharmacokinetic/pharmacodynamic models from already available systems biology
      models. The approach used for model reduction is proper lumping of the system's
      states and is based on a search through the possible combinations of lumps. To
      avoid combinatorial explosion, a heuristic, greedy search strategy is employed
      and comparison with the full exhaustive search provides evidence that it performs
      well. The method takes advantage of an apparent property of this kind of systems
      that lumps remain consistent over different levels of order reduction. Advantages
      of the method presented include: the variables and parameters of the reduced
      model retain a specific physiological meaning; the algorithm is automatic and
      easy to use; it can be used for nonlinear models and can handle parameter
      uncertainty and constraints. The algorithm was applied to a model of NF-B
      signalling pathways in order to demonstrate its use and performance. Significant
      reduction was achieved for the example model, while agreement with the original
      model was proportional to the size of the reduced model, as expected. The results
      of the model reduction were compared with a published, intuitively reduced model
      of NF-B signalling pathways and were found to be in agreement, in terms of the
      identified key species for the system's kinetic behaviour. The method may provide
      useful insights which are complementary to the intuitive reduction approach,
      especially in large systems.

PMID- 19154084
TI  - Moment-closure approximations for mass-action models.
AB  - Although stochastic population models have proved to be a powerful tool in the
      study of process generating mechanisms across a wide range of disciplines, all
      too often the associated mathematical development involves nonlinear mathematics,
      which immediately raises difficult and challenging analytic problems that need to
      be solved if useful progress is to be made. One approximation that is often
      employed to estimate the moments of a stochastic process is moment closure. This
      approximation essentially truncates the moment equations of the stochastic
      process. A general expression for the marginal- and joint-moment equations for a
      large class of stochastic population models is presented. The generalisation of
      the moment equations allows this approximation to be applied easily to a wide
      range of models. Software is available from http://pysbml.googlecode.com/ to
      implement the techniques presented here.

PMID- 19154085
TI  - Chemical analysis of endolymph and the growing otolith: fractionation of metals
      in freshwater fish species.
AB  - The fractionation of metals from water to otolith is an area of research that has
      received relatively limited attention, especially in freshwater systems. The
      objectives of the present research were to study the metal partitioning between
      otolith and endolymph of two freshwater species: Lake trout (Salvelinus
      namaycush), and burbot (Lota lota). We also included the chemical analyses of
      water and blood from fish of the same species collected in the same area but
      during different years. These results provide insight regarding the partition of
      metals between water and fish. This is one of the first studies to provide a
      range of trace metal concentrations for endolymph and the growing otolith (both
      aragonite and vaterite) and to directly measure otolith-endolymph partition
      coefficients for freshwater fish. The trace elements (Mg, Sr, and Ba) most often
      used as otolith elemental tracers were the ones with the lowest uptake from water
      to blood. We found that endolymph and whole blood had similar metal
      concentrations, with Mg and Fe being the only elements enriched in whole blood.
      Results showed few significant differences in trace metal content between wild
      lake trout and burbot endolymph (except for K, Mg, and Ba), but significant
      differences existed between their aragonitic otoliths. These results suggest two
      different crystallization processes in these species or the presence of different
      proteins (and/or organic matrices) that would selectively influence elemental
      incorporation in the otoliths.

PMID- 19154086
TI  - Participation of nitric oxide in different models of experimental hypertension.
AB  - This review concerns the role of nitric oxide (NO) in the pathogenesis of
      different models of experimental hypertension (NO-deficient, genetic, salt
      dependent), which are characterized by a wide range of etiology. Although the
      contribution of NO may vary between different models of hypertension, a unifying
      characteristic of these models is the presence of oxidative stress that
      participates in the maintenance of elevated arterial pressure and seems to be a
      common denominator underlying endothelial dysfunction in various forms of
      experimental hypertension. Besides the imbalance between the endothelial
      production of vasorelaxing and vasoconstricting compounds as well as the relative
      insufficiency of vasodilator systems to compensate augmented vasoconstrictor
      systems, there were found numerous structural and functional abnormalities in
      blood vessels and heart of hypertensive animals. The administration of
      antihypertensive drugs, antioxidants and NO donors is capable to attenuate blood
      pressure elevation and to improve morphological and functional changes of
      cardiovascular system in some but not all hypertensive models. The failure to
      correct spontaneous hypertension by NO donor administration reflects the fact
      that sympathetic overactivity plays a key role in this form of hypertension,
      while NO production in spontaneously hypertensive rats might be enhanced to
      compensate increased blood pressure. A special attention should be paid to the
      modulation of sympathetic nervous activity in central and peripheral nervous
      system. These results extend our knowledge on the control of the balance between
      NO and reactive oxygen species production and are likely to be a basis for the
      development of new approaches to the therapy of diseases associated with NO
      deficiency.

PMID- 19154087
TI  - AMN 082, an agonist of mGluR7, exhibits mixed anti- and proconvulsant effects in
      developing rats.
AB  - Metabotropic glutamate receptors (mGluRs) represent a potential therapeutic
      target. Possible anticonvulsant action of AMN 082, an agonist of mGluR7 subtype,
      was studied in immature rats using pentylenetetrazol (PTZ)-induced seizures as a
      model. Five age groups of rats (7-, 12-, 18-, 25-day-old and adult animals) were
      pretreated with AMN 082 in doses of 0.5, 1, 2, and 5 mg/kg i.p. and 30 min later
      PTZ was administered (100 mg/kg s.c.). Controls received saline instead of the
      agonist. AMN 082 did not exhibit clear anticonvulsant action with the exception
      of suppression of the tonic phase of generalized tonic-clonic seizures (GTCS) in
      12-day-old rats. Shorter latencies of GTCS after AMN 082 pretreatment indicate a
      proconvulsant action. Involuntary movements (mostly tremor) appeared after AMN
      082 before PTZ administration, therefore we performed another experimental series
      with AMN 082 only (1, 2, 5, and 10 mg/kg i.p.). During 60-min observation period
      tremor appeared in all age groups; sensitivity to this action decreased with age
      from the 2 mg/kg dose in 7- and 12-day-old rats to the 10 mg/kg dose in adult
      rats. Mixed anti- and proconvulsant actions of AMN 082 together with unwanted
      motor effects makes clinical use of this drug highly improbable.

PMID- 19154088
TI  - Real time RT-PCR with a newly designed set of primers confirmed the presence of
      2b and 2x/d myosin heavy chain mRNAs in the rat slow soleus muscle.
AB  - In order to re-evaluate the presence and relative quantity of 2b and 2x/d myosin
      heavy chain (MyHC) transcripts in rat slow soleus muscle by using real time RT
      PCR we have compared the available relevant cDNA sequences and designed a new set
      of primers having similar melting temperatures, matching separate MyHC exons in
      the regions of maximal differences in MyHC coding sequences, and containing G or
      C at the 3 -end. These also yielded PCR products of corresponding length, which
      is an important requirement for real time RT-PCR quantification. The experiments
      were performed on 8-month-old inbred female Lewis strain rats used in our current
      study of regenerating transplanted muscles. The real time RT-PCR measurement
      confirmed the expression of all four MyHC mRNAs (type 1, 2a, 2x/d and 2b) in both
      fast extensor digitorum longus and slow soleus muscles, although in the soleus
      muscle of adult rats, only type 1 and 2a protein isoforms can be usually
      detected.

PMID- 19154089
TI  - Animal experimentation: weighing the benefits against the suffering.

PMID- 19154090
TI  - Toward a new toxicology - evolution or revolution?
AB  - This essay summarises the author's thoughts on the current paradigm change in
      toxicology. The driving factors and mechanisms of this change, and obstacles to
      it, are discussed. Current developments are discussed on the basis of some key
      assumptions in Thomas Kuhn's famous book, The Structure of Scientific
      Revolutions. The author's personal view is that there is clear evidence that
      revolutionary changes in regulatory toxicology are emerging.

PMID- 19154091
TI  - An in vitro tier evaluation for the identification of cosmetic ingredients which
      are not ocular irritants.
AB  - A tier evaluation system was assessed as an alternative method for the
      identification of cosmetic ingredients which are not ocular irritants. The system
      employed monolayer cultures of SIRC cells, an established cell line originally
      derived from the rabbit cornea, and a three-dimensional living dermal model
      (LDM), MATREXtrade mark, which consists of human dermal fibroblasts in a
      contracted collagen lattice. Effects on the cell monolayer cultures were
      determined by using SIRC cell-Crystal Violet staining (SIRC-CVS), and effects on
      the LDM were assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. A non-irritating ingredient was defined
      as a compound having a maximal average total score (MAS) of 5 or less in the
      Draize eye test, as this is the criterion used in the Japanese draft guidance for
      evaluating cosmetic ingredients. Among 34 test substances with known
      characteristics, 30 were classified accurately. Based on these encouraging
      results, the possibility of simplifying the MTT assay on the LDM for more
      practical use, by selecting only three concentration levels to discriminate non
      irritants from irritants, was assessed. The simplified method, involving a three
      dose set (the three-dose method), was confirmed as being suitable for the
      identification of non-irritating ingredients, with triethanolamine used as a
      negative reference standard. Finally, the LDM was used to evaluate compounds at
      similar concentrations to those tested in vivo, aiming to predict the
      concentration at which an ingredient can be formulated into products without
      causing eye irritation. On the basis of previous validation data and our
      additional results, it was found that test samples that resulted in a cell
      viability of 50% or more in this model, could be classified as non-irritating
      ingredients. In all, these results indicate that the tier evaluation system may
      be suitable for the evaluation of ingredients intended to be used in cosmetics
      and medicated cosmetics in Japan.

PMID- 19154092
TI  - Technical modification of the Balb/c 3T3 cell transformation assay: the use of
      serum-reduced medium to optimise the practicability of the protocol.
AB  - The two-stage Balb/c 3T3 model of cell transformation can mimic the two-stage
      carcinogenicity bioassay, and has been recognised as a screening method for
      detecting potential tumour initiators and promoters. A technical modification to
      the original protocol (which involved the use of M10F medium, consisting of MEM
      plus 10% fetal bovine serum [FBS]) has been previously proposed, in order to
      increase its efficacy, namely: the introduction of enriched, serum-reduced medium
      (DF2F medium, comprising DMEM/F12 plus 2% FBS and other supplements). The aim of
      this study was to further modify the protocol, so as to attain higher
      practicability for the assay. The protocol was further optimised by: a) reducing
      the number of plates required, through the use of larger plates; b) reducing the
      cost of the assay by retaining the reduced serum concentration and by using
      2microg/ml insulin, rather than the more-complex insulin-transferrin-ethanolamine
      sodium selenite (ITES) supplement (i.e. DF2F2I medium); and c) extending the
      culture period from 24-25 days to 31-32 days, resulting in clearer foci (the
      number of medium changes did not increase, as less-frequent medium changes were
      performed during the extended culture period). Growth curve construction revealed
      that variations in the saturation densities of the parental Balb/c 3T3 cell line
      and its three transformed clones were highest when M10F medium was replaced with
      DF2F2I medium just before cells reached confluence. We applied this newly
      optimised protocol to the assessment of: a) the tumour initiating activity of 3
      methylcholanthrene (MCA), N-methyl-N'-nitro-N-nitrosoguanidine, mitomycin C,
      methylmethane sulphonate, CdCl(2) and phenacetin, combining a post-treatment of
      100ng/ml 12-O-tetradecanoylphorbol-13-acetate at the promotion stage; and b) the
      tumour promoting activity of insulin, lithocholic acid, CdCl(2) and
      phenobarbital, with pre-treatment of 0.2microg/ml MCA at the initiation stage. In
      the present study, only phenobarbital was negative when tested by using the
      modified protocol.

PMID- 19154094
TI  - Batch safety testing of veterinary vaccines - potential welfare implications of
      injection volumes.
AB  - This study examines the volumes administered by injection during the batch safety
      testing of veterinary vaccines according to the methods laid down in European
      Pharmacopoeia monographs. These are compared with maximum dose volumes
      recommended in good practice guidelines. The volumes administered during safety
      tests frequently exceeded recommended maximums, giving rise to concerns that
      these tests may seriously compromise animal welfare. This was particularly the
      case for live liquid vaccines and for vaccines recommended for intramuscular
      injection. The volumes used in testing vaccines for avian species exceeded the
      recommended maximums by the greatest amount. The administration of test doses
      should be performed in a way that minimises pain and discomfort. The refinement
      of tests by dividing large dose volumes and delivering them over multiple sites
      is discussed, but it is recognised that there are technical limitations, which in
      some cases may cause difficulties with fulfilling the purpose of the tests.
      Previously, the relevance of batch safety tests has been widely criticised, due
      to a lack of evidence that they contribute to the safety of veterinary medicines.
      By showing that the conduct of target animal safety tests can involve injection
      volumes that compromise the welfare of the animals involved, this analysis
      highlights the need for a more critical assessment of the necessity and
      justification for these tests.

PMID- 19154093
TI  - The effects of terahertz radiation on human keratinocyte primary cultures and
      neural cell cultures.
AB  - Terahertz (THz) frequencies are found in a previously underexploited region of
      the radiation spectrum. This non-ionising energy is now being employed in medical
      imaging, so the possibility of adverse effects on human skin was evaluated.
      Primary cultures of normal human keratinocytes (NHKs) express adhesion molecules
      that comprise part of the natural barrier function of the skin. The effects of
      exogenous agents on this barrier function can be measured. The ND7/23 cell line,
      which displays the characteristics of sensory neurones, can proliferate in the
      undifferentiated state, but can be induced to differentiate and develop neurite
      like projections. Previous studies with NHK and neural cell cultures produced no
      evidence of the inability of these cells to differentiate and form a barrier
      following THz exposure. The cells were exposed to 0.14THz radiation for times
      varying from 10 minutes to 24 hours. For each 80-nanosecond pulse, the cells were
      exposed to a peak power of between 24 and 62mW/cm(2), i.e. a total energy at peak
      power of 345J, or 86J at average power over 24 hours. No changes in cell activity
      occurred, as monitored with the resazurin reduction assay, or with the barrier
      function of the human corneal cells, as measured with the fluorescein leakage
      assay. The monitoring of differentiation by using an assay for cornified envelope
      formation, revealed no adverse effects. Glutathione (GSH) and heat shock protein
      70 levels were examined before and after differentiation, to determine the degree
      of the stress response, with the effects of UVB radiation as a control. UVB
      induced a stress response, as did heat shock treatment at 43 degrees C, whilst
      0.15THz radiation, even after 24 hours of exposure, did not. Repeated exposure to
      THz radiation at this level, also resulted in no detectable adverse reactions.

PMID- 19154095
TI  - The Home Office Statistics for 2007 - mutant mice and fishy tales.
AB  - The publication of the Statistics of Scientific Procedures on Living Animals
      Great Britain 2007 earlier this year, revealed once again that animal
      experimentation is on the up. This can mainly be attributed to the continuing use
      of genetically modified mice and an increased interest in investigations and
      tests involving fish. Here, some of the general trends are described,
      developments of interest are discussed, and the implications of the statistics
      are explored.

PMID- 19154096
TI  - The need for the establishment of a Brazilian Centre for the Validation of
      Alternative Methods (BraCVAM).
AB  - Brazil has recently approved legislation for regulating experimental animal use.
      On the other hand, it is a requirement that the safety of many products on the
      market is controlled on the basis of animal testing. Some groups at official
      laboratories, universities and industries are studying alternative methods, but
      there is no approved mechanism for funding collaborative studies, nor is there an
      institution responsible for coordinating these studies. These shortcomings
      obstruct the development of these assays in Brazil. The creation of a Brazilian
      Centre for the Validation of Alternative Methods (BraCVAM) would facilitate the
      development and validation of tests in all the institutions working on
      alternative methods in Brazil, and could also offer support to other Latin
      American countries.

PMID- 19154097
TI  - Reviewing existing knowledge prior to conducting animal studies.
AB  - Highly polarised viewpoints about animal experimentation have often prevented
      agreement. However, important common ground between advocates and opponents was
      demonstrated within a discussion forum hosted at www.research-methodology.org.uk
      in July-August 2008, by the independent charity, SABRE Research UK. Agreement
      existed that many animal studies have methodological flaws - such as
      inappropriate sample sizes, lack of randomised treatments, and unblinded outcome
      assessments - that may introduce bias and limit statistical validity. There was
      also agreement that systematic reviews of the human utility of animal models
      yield the highest quality of evidence, as their reliance on methodical and
      impartial methods to select significant numbers of animal studies for review,
      serves to minimise bias. Unfortunately, disagreement remained that animal
      experimental licence applications should reference systematic reviews of existing
      studies, before approval. The UK Medical Research Council requires that
      researchers planning human clinical trials must reference such reviews of related
      previous work. Existing knowledge is thereby fully and appropriately utilised,
      and redundant experimentation is avoided. However, objections were raised that a
      similar requirement would interfere with animal experimental licensing, because,
      to date, there have been very few systematic reviews of animal studies. In fact,
      the relative dearth of such reviews is a matter of considerable concern, and may
      partially explain the very poor human success rates of drugs that appear safe
      and/or efficacious in animal trials. Nevertheless, the disturbing number of human
      trials which have proceeded concurrently with, or prior to, animal studies, or
      have continued despite equivocal evidence of efficacy in animals, clearly
      demonstrate that many researchers fail to conduct adequate prior reviews of
      existing evidence. Where neither sufficient primary studies, nor systematic
      reviews of such studies, exist, for citation within a licence application,
      researchers should be able to provide evidence of this shortcoming, and,
      concurrently, demonstrate that the available literature and evidence have been
      adequately reviewed. This should also enable them to clearly demonstrate the need
      and scientific appropriateness of their proposed study, the validity of its
      design, and - importantly - that the benefits are reasonably likely to exceed the
      animal welfare, bioethical and financial costs. Invasive animal studies should
      never be permitted solely on the basis of less probable, speculative or
      intangible human benefits, or the mere satisfaction of scientific curiosity.

PMID- 19154098
TI  - The way forward for reproductive/developmental toxicity testing.

PMID- 19154099
TI  - Developmental and reproductive toxicity testing: animal studies are not
      predictive for humans.

PMID- 19154100
TI  - The need for realism in reproductive toxicity testing.

PMID- 19154101
TI  - Developmental toxicity testing: protecting future generations?
AB  - A recent editorial is discussed, which implied that animal-based developmental
      and reproductive toxicology tests will continue to be crucial, that the
      thalidomide disaster could have been prevented by more animal testing, and that
      tests on juvenile animals would help to protect children (as developing adults)
      from the adverse effects of pharmaceuticals. It is argued that animal tests in
      these scientific areas do not provide reliable data that are predictive for human
      responses and, even if they did, the tests are too expensive and time-consuming
      for application to the very large number of substances that need to be tested. It
      is estimated there are already more than 100,000 man-made chemicals to which
      humans may be exposed on a regular basis, and it is therefore widely accepted
      that in vivo developmental toxicology could not possibly be used to assess all
      new and existing chemical substances, due to the scale of its demand upon time
      and resources. It is therefore imperative that alternatives such as those
      outlined above are embraced, further developed, accepted and used - as a matter
      of urgency.

PMID- 19154102
TI  - Comparative studies on the structural features of O-glycans between leukemia and
      epithelial cell lines.
AB  - Recently, we developed an automated apparatus for rapid releasing of O-glycans
      from mucin-type glycoproteins and proteoglycans ( Anal. Biochem. 2007 , 362 , 245
      - 251 ; 2007 , 371 , 52 - 61 ). In the present paper, we released O-glycans from
      some leukemia and epithelial cells using the apparatus, and compared the profiles
      of O-glycans among these cells after fluorescent labeling of the released glycans
      with 2-aminobenzoic acid. The fluorescent labeled glycans were analyzed using a
      combination of HPLC and off-line MALDI-(QIT)TOF mass spectrometry We found that
      leukemia cells generally showed simple glycan profiles and commonly contained
      sialyl-T (NeuAcalpha2-3Galbeta1-3GalNAc) and disialyl-T (NeuAcalpha2-3Galbeta1
      3(NeuAcalpha2-6)GalNAc) antigens as major O-glycans. In contrast, epithelial
      cancer cell lines usually showed extremely complex profiles. We found that
      polylactosamine-type O-glycans were abundantly present in MKN45 cells.
      Especially, we found characteristic glycans, of which Galbeta1-3 residue of core1
      structure is modified with biantennary polylactosamine units. In contrast, this
      cell line did not contain polylactosamine-type N-glycans ( J. Proteome Res. 2006
      , 5 , 88 - 97 ). These results suggest that the different biosynthetic pathways
      for N- and O-glycans are proposed. The method presented here will accelerate the
      speed for comprehensive analysis of O-glycans in biological samples and will be a
      powerful tool for clinical/biochemical analysis in cancer biology.

PMID- 19154103
TI  - Impact of innovative controlled atmosphere storage technologies and postharvest
      treatments on volatile compound production in cv. Pinova apples.
AB  - Organically grown apples cv. Pinova harvested at two different dates were stored
      at 1.3 degrees C for up to 4 months in air, up to 7 months in ULO (1.5 kPa of
      O(2) and 1.3 kPa of CO(2)) and in dynamic controlled atmosphere (DCA) conditions
      (0.4-0.6 kPa of O(2) and 0.6-0.8 kPa of CO(2)); the DCA storage method involved
      the use of a chlorophyll fluorescence monitoring system in order to detect low
      O(2) stress in apples and to allow for the dynamic adaptation of storage
      atmosphere to O(2) levels that were lower than in ULO but still tolerated by
      fruits. A postharvest 1-MCP treatment (for 24 h at 1.3 degrees C) and a hot water
      treatment (for 180 s at 50 degrees C) were also tested on apples stored afterward
      in ULO and air, respectively. Volatile compounds isolated from the pulp of fruits
      were measured after 4 and 7 months, just upon removal from storage and after 11
      days at 22 degrees C. Total amount of aroma compounds detected in apples stored
      in DCA was markedly higher (from 2- to 4-fold) than in fruits exposed to 1-MCP +
      ULO but, at most sampling times, significantly lower than in ULO fruits. Moderate
      differences in storage atmosphere composition between ULO and DCA significantly
      affected both total amount and profile of volatile esters. Analogous effects were
      observed on the alcohol precursors of the main esters. Exposure to 1-MCP
      inhibited biosynthesis of straight-chain esters more than that of branched-chain
      esters. The hot water treatment did not seem to produce marked changes in
      volatile composition after four months of air storage, except for a sharp
      accumulation of aldehydes during the shelf-life time. DCA storage technology,
      besides avoiding any chemical treatment, can preserve apple aroma compounds
      better than 1-MCP + ULO during long-term storage.

PMID- 19154104
TI  - Fungal chitin-glucan from Aspergillus niger efficiently reduces aortic fatty
      streak accumulation in the high-fat fed hamster, an animal model of nutritionally
      induced atherosclerosis.
AB  - The effects of chitin-glucan (CG) on early atherosclerosis, cardiac production of
      superoxide anion, and hepatic antioxidant enzymes were studied in an animal model
      of atherosclerosis. Three groups of 12 hamsters were fed an atherogenic diet for
      12 weeks. They received by gavage either water (control group) or CG in water at
      a dose of 21.4 mg/kg BW x d-1 of chitin-glucan (CG ld) or 42.8 mg/kg BW x d-1 (GG
      hd). CG did not affect plasma cholesterol but lowered triglycerides. It also
      strongly reduced the area of aortic fatty streak deposition by 87-97%, cardiac
      production of superoxide anion by 25% and liver MDA by 77-85%, and enhanced liver
      superoxide dismutase activity by 7-45% and glutathionne peroxidase activity by 38
      120%. These findings support the view that chronic consumption of chitin-glucan
      has potential beneficial effects with respect to the development of
      atherosclerosis. The underlying mechanism is related mainly to improving the
      antioxidant status.

PMID- 19154105
TI  - Identification of predominant odorants in thai desserts flavored by smoking with
      "Tian Op", a traditional Thai scented candle.
AB  - "Tian Op", a traditional Thai scented candle, is used for the smoking and
      flavoring of sweets, cakes, and other desserts for the purpose of adding a unique
      aroma to the final product. Gas chromatography-olfactometry, aroma extract
      dilution analysis, and GC-MS were applied to identify the potent odorants in two
      types of traditional Thai desserts ("num dok mai" and "gleep lum duan") prepared
      using a Tian Op smoking process. On the basis of the results of AEDA and
      calculated odor-activity values, the predominant odorants in the Tian Op flavored
      desserts were vinyl ketones (C(5)-C(9)), n-aldehydes (C(5)-C(11)), (E)-2
      unsaturated aldehydes (C(8)-C(11)), and omega-1-unsaturated aldehydes (C(8) and
      C(9)). Sensory studies of model mixtures confirmed the importance of n-aldehydes,
      omega-1-unsaturated aldehydes, and guaiacol as predominant odorants; however, the
      results showed that vinyl ketones and (E)-2-unsaturated aldehydes, despite having
      high odor-activity values, may be of only minor importance in the typical aroma
      profiles of traditional Tian Op smoked desserts.

PMID- 19154106
TI  - Trapping effects of green and black tea extracts on peroxidation-derived carbonyl
      substances of seal blubber oil.
AB  - Green and black tea extracts were employed to stabilize seal blubber oil at 60
      degrees C for 140 h. On the basis of the headspace SPME-GC-MS analysis, with the
      addition of green/black tea extracts, the contents of acetaldehyde, acrolein,
      malondialdehyde, and propanal, four major lipid peroxidation products, were
      reduced. The inhibition rates of acrolein formation by green tea and black tea
      extracts were 98.40 and 96.41% respectively, and were 99.17 and 98.16% for
      malondialdehyde, respectively, much higher than the inhibition of the formation
      of acetaldehyde and propanal. Because malondialdehyde and acrolein are reactive
      carbonyl species (RCS) and recent studies have suggested that phenolics can
      directly trap RCS, this study also investigated whether green tea polyphenols can
      trap acrolein or not. Acrolein was reduced by 90.30% in 3 h of incubation with (
      )-epigallocatechin-3-gallate (EGCG). Subsequent LC-MS analysis revealed the
      formation of new adducts of equal molars of acrolein and EGCG. The reaction site
      for acrolein was elucidated to be the A ring of EGCG as evidenced by LC-MS/MS
      analysis and by testing of the acrolein-trapping capacities of the analogous
      individual A, B, and C rings of EGCG. Thus, EGCG's direct trapping of RCS may
      also contribute to the significant reduction of acrolein and other aldehydes in
      the peroxidation of seal blubber oil.

PMID- 19154107
TI  - Dried blood spots as a sample collection technique for the determination of
      pharmacokinetics in clinical studies: considerations for the validation of a
      quantitative bioanalytical method.
AB  - A novel approach has been developed for the quantitative determination of
      circulating drug concentrations in clinical studies using dried blood spots (DBS)
      on paper, rather than conventional plasma samples. A quantitative bioanalytical
      HPLC-MS/MS assay requiring small blood volumes (15 microL) has been validated
      using acetaminophen as a tool compound (range 25 to 5000 ng/mL human blood). The
      assay employed simple solvent extraction of a punch taken from the DBS sample,
      followed by reversed phase HPLC separation, combined with selected reaction
      monitoring mass spectrometric detection. In addition to performing routine
      experiments to establish the validity of the assay to internationally accepted
      criteria (precision, accuracy, linearity, sensitivity, selectivity), a number of
      experiments were performed to specifically demonstrate the quality of the
      quantitative data generated using this novel sample format, namely, stability of
      the analyte and metabolites in whole human blood and in DBS samples; effect of
      the volume of blood spotted, the device used to spot the blood, or the
      temperature of blood spotted. The validated DBS approach was successfully applied
      to a clinical study (single oral dose of 500 mg or 1 g acetaminophen).

PMID- 19154108
TI  - Ostreocin-D impact on globular actin of intact cells.
AB  - Ostreocin-D, discovered in the past decade, is a marine toxin produced by
      dinoflagellates. It shares structure with palytoxin, a toxic compound responsible
      for the seafood intoxication named clupeotoxism. At the cellular level, the
      action sites and pharmacological effects for ostreocin-D are still almost
      unknown. Previously, we demonstrated that these toxins change the filamentous
      actin cytoskeleton, which is essential for multiple cellular functions. However,
      nothing has yet been reported about what happens with the unpolymerized actin
      pool. Here (i) the effects induced by ostreocin-D on unpolymerized actin, (ii)
      the Ca2+ role in such a process, and (iii) the cytotoxic activity of ostreocin-D
      on the human neuroblastoma BE(2)-M17 cell line are shown for the first time.
      Fluorescently labeled DNase I was used for staining of monomeric actin prior to
      detection with both laser-scanning cytometry and confocal microscopy techniques.
      Cellular viability was tested through a microplate metabolic activity assay.
      Ostreocin-D elicited a rearrangement of monomeric actin toward the nuclear
      region. This event was not accompanied by changes in its content. In addition,
      the presence or absence of external Ca2+ did not change these results. This toxin
      was also found to cause a decrease in the viability of neuroblastoma cells, which
      was inhibited by the specific blocker of Na+/K+-ATPase, ouabain. All these
      responses were comparable to those obtained with palytoxin under identical
      conditions. The data suggest that ostreocin-D modulates the unassembled actin
      pool, activating signal transduction pathways not related to Ca2+ influx in the
      same way as palytoxin.

PMID- 19154109
TI  - Magnetism of C adatoms on BN nanostructures: implications for functional
      nanodevices.
AB  - Spin-polarized density functional calculations reveal that magnetism can be
      induced by carbon adatoms on boron nitride nanotubes (BNNTs) and BN hexagonal
      sheets. As a result of the localization of impurity states, these hybrid sp
      electron systems are spin-polarized, with a local magnetic moment of 2.0 mu(B)
      per C adatom regardless of the tube diameter and the bonding between the C atom
      and the BNNTs/BN sheets. An analysis of orbital hybridization indicates that two
      valence electrons participate in the bonding and the remaining two electrons of
      the C adatom are confined at the adsorption site and contribute to the magnetism
      accordingly. The effective interaction distance between the C-induced magnetic
      moments is evaluated. In terms of the diffusion barrier and the adsorption energy
      of C adatoms on the BN nanotubes/sheets, a fabrication method for BN-C-based
      functional nanodevices is proposed, and a series of virtual building blocks for
      functional devices are illustrated.

PMID- 19154111
TI  - Inefficient crystal packing in chiral [Ru(phen)(3)](PF(6))(2) enables oxygen
      molecule quenching of the solid-state MLCT emission.
AB  - The molecular oxygen quenching of the solid-state emission from pure crystals of
      Delta-Ru(phen)(3)(PF(6))(2), Lambda-Ru(phen)(3)(PF(6))(2), and racemic
      Ru(phen)(3)(PF(6))(2) (phen = 1,10-phenanthroline) was studied by emission
      spectroscopy. Crystals of the pure enantiomers exhibit significant and nearly
      identical emission-intensity quenching [0.36(2) and 0.33(2), respectively] in the
      presence of air [where the fraction quenched is (I(nitrogen) -
      I(air))/I(nitrogen)]; in comparison, the racemic compound shows a much lower
      value [0.05(2)]. The large difference in the quenching behavior is a result of
      major structural differences between the two chiral salts and the racemic salt.
      The chiral compounds crystallize in the space groups P4(1) and P4(3),
      respectively, with toluene and acetonitrile molecules in the lattice that can be
      partially removed to create void-space channels. These open channels allow the
      diffusion of oxygen molecules within the crystals and enable efficient emission
      quenching that is not possible in the closely packed racemic salt. Lifetime
      measurements, thermal gravimetric analysis, and single-crystal X-ray structure
      determinations support these conclusions.

PMID- 19154110
TI  - Peptide quantification using 8-plex isobaric tags and electron transfer
      dissociation tandem mass spectrometry.
AB  - Isobaric tags for absolute and relative quantitation (iTRAQ) allow for
      simultaneous relative quantification of peptides from up to eight different
      samples. Typically peptides labeled with 8-plex iTRAQ tags are pooled and
      fragmented using beam-type collision activated dissociation (CAD) which, in
      addition to cleaving the peptide backbone bonds, cleaves the tag to produce
      reporter ions. The relative intensities of the reporters are directly
      proportional to the relative abundances of each peptide in the solution phase.
      Recently, studies using the 4-plex iTRAQ tagging reagent demonstrated that
      electron transfer dissociation (ETD) of 4-plex iTRAQ labeled peptides cleaves at
      the N-C alpha bond in the tag and allows for up to three channels of
      quantification. In this paper we investigate the ETD fragmentation patterns of
      peptides labeled with 8-plex iTRAQ tags. We demonstrate that upon ETD, peptides
      labeled with 8-plex iTRAQ tags fragment to produce unique reporter ions that
      allow for five channels of quantification. ETD-MS/MS of these labeled peptides
      also produces a peak at 322 m/z which, upon resonant excitation (CAD), gives rise
      to all eight iTRAQ reporter ions and allows for eight channels of quantification.
      Comparison of this method to beam-type CAD quantification shows a good
      correlation (y = 0.91x + 0.01, R(2) = 0.9383).

PMID- 19154112
TI  - Orthogonal "relay" reactions for designing functionalized soft nanoparticles.
AB  - The combination of reversible addition-fragmentation chain transfer (RAFT)
      chemistry followed by thiol-based "click" chemistry, known as an orthogonal
      "relay" reaction as one step complements the other, was used to produce surface
      functionalized soft nanoparticles. Thiocarbonyl thio compounds were first used in
      the presence of vinyl monomers and a source of radicals to control the growth of
      the polymeric chains (via the RAFT process) and then reduced to thiols and
      utilized as a handle for functionalization of the resulting polymer chain ends
      (via a thiol-based click reaction). Both reactions occur under mild conditions
      and offer excellent control over the properties of the final product, and the
      thiol addition shows all the benefits of a click reaction, without requiring the
      use of a catalyst. This simple chemistry opens up the route to the production of
      a wide range of functional materials, and the concept is illustrated by the
      formation of nanoparticle-based gels, fluorescent-tagged particles, and protein
      nanoparticle conjugates.

PMID- 19154114
TI  - Synthesis of rod-shaped gold nanorattles with improved plasmon sensitivity and
      catalytic activity.
AB  - We prepared rod-shaped gold nanorattles solid gold nanorods surrounded by a thin
      gold shell using a galvanic replacement process starting with silver-coated gold
      nanorods. These structures are very promising candidates for catalytic
      applications and optimized plasmon sensors. They combine the advantages of rods
      (low plasmon resonance frequency, large polarizability, small damping) with the
      high surface area of hollow structures. The plasmon sensitivity to changes in the
      dielectric environment is up to 50% higher for gold nanorattles compared to gold
      nanorods with the same resonance frequency and 6x higher than for plasmons in
      spherical gold nanoparticles. The catalytic activity measured for the reduction
      of p-nitrophenol is 4x larger than for bare gold nanorods.

PMID- 19154113
TI  - Diels-Alder exo selectivity in terminal-substituted dienes and dienophiles:
      experimental discoveries and computational explanations.
AB  - The Diels-Alder reactions of a series of silyloxydienes and silylated dienes with
      acyclic alpha,beta-unsaturated ketones and N-acyloxazolidinones have been
      investigated. The endo/exo stereochemical outcome is strongly influenced by the
      substitution pattern of the reactants. High exo selectivity was observed when the
      termini of the diene and the dienophile involved in the shorter of the forming
      bonds were both substituted, while the normal endo preference was found
      otherwise. The exo-selective asymmetric Diels-Alder reactions using Evans'
      oxazolidinone chiral auxiliary furnished a high level of pi-facial selectivity in
      the same sense as their well-documented endo-selective counterparts.
      Computational results for these Diels-Alder reactions were consistent with the
      experimental endo/exo selectivity in most cases. A twist-asynchronous model
      accounts for the geometries and energies of the computed transition structures.

PMID- 19154115
TI  - Films of agarose enable rapid formation of giant liposomes in solutions of
      physiologic ionic strength.
AB  - This paper describes a method to form giant liposomes in solutions of physiologic
      ionic strength, such as phosphate buffered saline (PBS) or 150 mM KCl. Formation
      of these cell-sized liposomes proceeded from hybrid films of partially dried
      agarose and lipids. Hydrating the films of agarose and lipids in aqueous salt
      solutions resulted in swelling and partial dissolution of the hybrid films and in
      concomitant rapid formation of giant liposomes in high yield. This method did not
      require the presence of an electric field or specialized lipids; it generated
      giant liposomes from pure phosphatidylcholine lipids or from lipid mixtures that
      contained cholesterol or negatively charged lipids. Hybrid films of agarose and
      lipids even enabled the formation of giant liposomes in PBS from lipid
      compositions that are typically problematic for liposome formation, such as pure
      phosphatidylserine, pure phosphatidylglycerol, and asolectin. This paper
      discusses biophysical aspects of the formation of giant liposomes from hybrid
      films of agarose and lipids in comparison to established methods and shows that
      gentle hydration of hybrid films of agarose and lipids is a simple, rapid, and
      reproducible procedure to generate giant liposomes of various lipid compositions
      in solutions of physiologic ionic strength without the need for specialized
      equipment.

PMID- 19154116
TI  - Monovalent cation binding in the minor groove of DNA A-tracts.
AB  - The binding of five different monovalent cations to DNA oligomers containing A
      tracts, runs of four or more contiguous adenine residues, has been assessed by
      capillary electrophoresis, using the Replacement Ion method. In this method, a
      nonbinding cation in the background electrolyte is gradually replaced by a
      binding cation, keeping the ionic strength of the solution constant. Monovalent
      cation binding reduces the effective charge of an A-tract-containing oligomer,
      decreasing its free solution mobility. The cations bind in the A-tract minor
      groove, because the binding site can be blocked by the minor groove binding drug
      netropsin. Li(+), NH(4)(+), and Tris(+) ions bind to A-tracts with similar
      affinities; the binding of Na(+) ions is weaker, and K(+) ion binding is highly
      variable. Each A-tract appears to bind one monovalent cation upon saturation of
      the binding site(s). For a given cation, the apparent dissociation constants
      depend on A-tract sequence and orientation, but not on the phasing of the A
      tracts with respect to the helix repeat. Differences in the cooperativity of
      binding of the various cations to A-tracts with different sequences suggest that
      monovalent cation binding may be coupled with a conformational transition leading
      to the formation of the characteristic narrow minor groove A-tract structure.

PMID- 19154117
TI  - Processive and unidirectional translocation of monomeric UvsW helicase on single
      stranded DNA.
AB  - UvsW protein from bacteriophage T4 controls the transition from origin-dependent
      to origin-independent initiation of replication through the unwinding of R-loops
      bound to the T4 origins of replication. UvsW has also been implicated through
      genetic and biochemical experiments to play a role in DNA repair processes such
      as replication fork regression and Holliday junction branch migration. UvsW is
      capable of unwinding a wide variety of substrates, many of which contain only
      duplex DNA without single-stranded regions. Based on this observation, it has
      been suggested that UvsW is a dsDNA translocase. In this work we examine the
      ability of UvsW to translocate on ssDNA. Kinetic analysis indicates that the rate
      of ATP hydrolysis is strongly dependent on the length of the ssDNA lattice,
      whereas the K(M)-DNA remains relatively constant, demonstrating that UvsW
      translocates on ssDNA in an ATP-dependent fashion. Experiments using streptavidin
      blocks or poly dT sequences located at either end of the ssDNA substrate indicate
      that UvsW translocates in a 3' to 5' direction. Mutant competition and heparin
      trapping experiments reveal that UvsW is extremely processive during ATP-driven
      translocation with a half-life on the order of several minutes. Finally,
      functional assays provide evidence that UvsW is monomeric while translocating on
      ssDNA. The ability of UvsW to unwind DNA duplexes is likely to be mechanistically
      linked to its ability to processively translocate on ssDNA in a 3' to 5'
      unidirectional fashion.

PMID- 19154118
TI  - Symmetrical refolding of protein domains and subunits: example of the dimeric two
      domain 3-isopropylmalate dehydrogenases.
AB  - The refolding mechanism of the homodimeric two-domain 3-isopropylmalate
      dehydrogenase (IPMDH) from the organisms adapted to different temperatures,
      Thermus thermophilus (Tt), Escherichia coli (Ec), and Vibrio sp. I5 (Vib), is
      described. In all three cases, instead of a self-template mechanism, the high
      extent of symmetry and cooperativity in folding of subunits and domains have been
      concluded from the following experimental findings: The complex time course of
      refolding, monitored by Trp fluorescence, consists of a fast (the rate constant
      varies as 16.5, 25.0, and 11.7 min-1 in the order of Tt, Ec, and Vib IPMDHs) and
      a slow (the rate constants are 0.11, 0.80, and 0.23 min-1 for the three different
      species) first-order process. However, a burst increase of Trp fluorescence
      anisotropy to the value of the native states indicates that in all three cases
      the association of the two polypeptide chains occurs at the beginning of
      refolding. This dimeric species binds the substrate IPM, but the native-like
      interactions of the tertiary and quaternary structures are only formed during the
      slow phase of refolding, accompanied by further increase of protein fluorescence
      and appearance of FRET between Trp side chain(s) and the bound NADH. Joining the
      contacting arms of each subunit also takes place exclusively during this slow
      phase. To monitor refolding of each domain within the intact molecule of T.
      thermophilus IPMDH, Trp's (located in separate domains) were systematically
      replaced with Phe's. The refolding processes of the mutants were followed by
      measuring changes in Trp fluorescence and in FRET between the particular Trp and
      NADH. The high similarity of time courses (both in biphasicity and in their
      rates) strongly suggests cooperative folding of the domains during formation of
      the native three-dimensional structure of IPMDH.

PMID- 19154119
TI  - High-throughput sequencing of peptoids and peptide-peptoid hybrids by partial
      edman degradation and mass spectrometry.
AB  - A method for the rapid sequence determination of peptoids [oligo(N-substituted
      glycines)] and peptide-peptoid hybrids selected from one-bead-one-compound
      combinatorial libraries has been developed. In this method, beads carrying unique
      peptoid (or peptide-peptoid) sequences were subjected to multiple cycles of
      partial Edman degradation (PED) by treatment with a 1:3 (mol/mol) mixture of
      phenyl isothiocyanate (PITC) and 9-fluorenylmethyl chloroformate (Fmoc-Cl) to
      generate a series of N-terminal truncation products for each resin-bound peptoid.
      After PED, the Fmoc group was removed from the N-terminus and any reacted side
      chains via piperidine treatment. The resulting mixture of the full-length peptoid
      and its truncation products was analyzed by matrix-assisted laser desorption
      ionization (MALDI) mass spectrometry, to reveal the sequence of the full-length
      peptoid. With a slight modification, the method was also effective in the
      sequence determination of peptide-peptoid hybrids. This rapid, high-throughput,
      sensitive, and inexpensive sequencing method should greatly expand the utility of
      combinatorial peptoid libraries in biomedical and materials research.

PMID- 19154120
TI  - Synthesis of thiazolo- and 7,8-dihydrothiazolo[4,5-e]benzoisoxazoles.
AB  - The first examples of thiazolo[4,5-e]benzoisoxazoles are obtained from
      bromination of dihydrobenzo[d]isoxazol-4(5H)-one followed by cyclocondensation
      with thiourea, in the presence of DDQ. Analogously, cyclocondensation with
      thioamides provided 7,8-dihydrothiazolo[4,5-e]benzoisoxazoles. A 55-member
      library of these heterocycles is reported.

PMID- 19154121
TI  - Evaluation of lithium ion insertion reactivity via electrochromic diffraction
      based imaging.
AB  - A microscope-CCD setup has been developed as an analytical tool for the detection
      of diffraction from one-dimensional redox-active transition-metal oxide gratings
      prepared with a combination of microtransfer molding (microTM) and cathodic
      electrodeposition. The diffraction efficiencies (DE) of tungsten trioxide, WO3,
      and binary molybdenum-tungsten trioxide, Mo0.6W0.4O3, gratings were measured
      during Li+ insertion/deinsertion experiments performed with both cyclic
      voltammetry and chronoamperometry in 1 M LiClO4/propylene carbonate. The DE was
      evaluated in terms of the optical constants of the grating materials determined
      by spectroscopic ellipsometry (SE) measurements of Li+ insertion/deinsertion into
      unpatterned thin films. The effect of grating thickness and the amount of
      inserted charge on DE has been analyzed. The diffraction method is used to
      quantitatively estimate lithium ion diffusion coefficients of electrochemically
      active metal oxide gratings.

PMID- 19154122
TI  - Synthesis, crystal structures, and photoluminescent properties of the
      Cu(I)/X/alpha,omega-bis(benzotriazole)alkane hybrid family (X = Cl, Br, I, and
      CN).
AB  - This work focused on a systematic investigation of the influences of the spacer
      length of the flexible alpha,omega-bis(benzotriazole)alkane ligands and
      counteranions on the overall molecular architectures of hybrid structures that
      include Cu(I). Using the self-assembly of CuX (X = Cl, Br, I, or CN) with the
      five structurally related flexible organic ligands (L1-L5) under
      hydro(solvo)thermal conditions, we have synthesized and characterized 10
      structurally unique materials of the Cu(I)/X/alpha,omega-bis(benzotriazole)alkane
      organic-inorganic hybrid family, {[CuCl](2)(L1)}(n) (1), {[CuBr](L2)}(n) (2),
      {[CuCl](2)(L3)}(n) (3), {[CuI](2)(L4)}(n) (4), {[CuBr](2)(L4)}(n) (5),
      {[CuBr](3)(L5)}(n) (6), {[CuCN](2)(L1)}(n) (7), {[CuCl](4)(L2)}(n) (8),
      {[CuBr](4)(L2)}(n) (9), and {[CuCl](2)(L4)}(n) (10), by means of elemental
      analyses, X-ray powder diffraction, Fourier transform infrared spectroscopy,
      thermogravimetric analysis, and photoluminescence measurements. Single-crystal X
      ray analyses showed that the inorganic subunits in these compounds were
      {Cu(2)X(2)} binuclear clusters (1 and 2), {Cu(4)X(4)} cubane clusters (4, 5, and
      10), {CuX}(n) single chains (3 and 7), a {Cu(3)X(3)}(n) ladderlike chain (6), and
      unprecedented {Cu(8)X(8)}(n) ribbons (8 and 9). The increasing dimensionality
      from 1-D (1-4) to 2-D (5 and 6) to 3-D (7-10) indicates that the spacer length
      and isomerism of the bis(benzotriazole)alkane ligands play an essential role in
      the formation of the framework of the Cu(I) hybrid materials. The influence of
      counteranions and pi-pi stacking interactions on the formation and dimensionality
      of these hybrid coordination polymers has also been explored. In addition, all
      the complexes exhibit high thermal stability and strong fluorescence properties
      in the solid state at ambient temperature.

PMID- 19154123
TI  - 1,5-Alpha-D-mannoseptanosides, ring-size isomers that are impervious to alpha
      mannosidase-catalyzed hydrolysis.
AB  - 1,5-D-mannoseptanosyl di- and trisaccharide ring-size isomers of the
      corresponding mannopyranosyl oligosaccharides have been prepared. Remarkably,
      these compounds show no inhibition of the alpha-mannosidase-catalyzed hydrolysis
      of p-nitrophenyl-alpha-D-mannopyranoside.

PMID- 19154124
TI  - Continuous colorimetric assay for acetylcholinesterase and inhibitor screening
      with gold nanoparticles.
AB  - We report herein a new colorimetric assay method for acetylcholinesterase (AChE)
      activity and its inhibitor screening by making use of the following facts: (1)
      the aggregation of gold nanoparticles (Au-NPs) results in the red-shift of the
      plasmon absorption due to interparticle plasmon interactions and (2) AChE can
      catalyze the hydrolysis of acetylthiocholine into thiocholine which can induce
      the aggregation of Au-NPs. With this convenient method, the activity of AChE with
      a concentration as low as 0.6 mU/mL can be assayed. Moreover, this assay method
      is also useful for screening inhibitors of AChE. Given its simplicity and easy
      operation, this method may extend to high-throughput screening of AChE inhibitors
      and relevant drug discovery.

PMID- 19154125
TI  - Polymer-stabilized phospholipid vesicles with a controllable, pH-dependent
      disassembly mechanism.
AB  - In this letter, we report a facile method to prepare robust phospholipid vesicles
      using commonly available phospholipids that are stabilized via the formation of
      an interpenetrating, acid-labile, cross-linked polymer network that imparts a
      site for controlled polymer destabilization and subsequent vesicle degradation.
      The polymer network was formed in the inner lamella of the phospholipid bilayer
      using 2,2-di(methacryloyloxy-1-ethoxy)propane (DMOEP) and butyl methacrylate
      (BMA). Upon exposure to acidic conditions, the highly cross-linked polymer
      network was partially converted to smaller linear polymers, resulting in
      substantially reduced vesicle stability upon exposure to chemical and physical
      insults. Isolated polymers had pH-dependent-solubility in THF. Transmission
      electron microscopy and dynamic light scattering revealed time-dependent enhanced
      vesicle stability in high concentrations of surfactant and vacuum conditions at
      elevated pH, whereas exposure to acidic pH rapidly decreased the vesicle
      stability, with complete destabilization observed in less than 24 h. The
      resultant transiently stabilized vesicles may prove useful for enhanced drug
      delivery and chemical sensing applications and allow for improved physiological
      clearance.

PMID- 19154126
TI  - Encapsulation of myoglobin in a cetyl trimethylammonium bromide micelle in vacuo:
      a simulation study.
AB  - A recently published paper describes encapsulation of myoglobin into cetyl
      trimethylammonium bromide (CTAB) micelles by electrospray ionization followed by
      detection using mass spectrometry [Sharon, M., et al. (2007) J. Am. Chem. Soc.
      129, 8740-8746]. Here we present molecular dynamics simulations aimed at
      elucidating the structural transitions that accompany the encapsulation and
      dehydration processes. Myoglobin associates with CTAB surfactants in solution,
      but no complete reverse micelle is formed. Upon removal of most of the water and
      exposure of the system to vacuum, a stable protein-surfactant reverse micelle
      forms. The surfactants shield the protein to a large extent from dehydration
      related conformational changes, in the same manner that a water shell does, as
      previously described by Patriksson et al. [(2007) Biochemistry 46, 933-945].
      Solvated CTAB micelles undergo a rapid inversion when transported to the gas
      phase and form very stable reverse micelles, independent of the amount of water
      present.

PMID- 19154127
TI  - Effect of pH on water proton NMR relaxation in agmatine-containing
      poly(amidoamine) hydrogels.
AB  - Transverse and longitudinal relaxation times of water protons were measured and
      magnetization transfer experiments were performed on cross-linked amphoteric
      poly(amidoamine)s containing different proportions of agmatine side groups
      swollen in buffer media with pH values in the 1.4-8.5 range in order to obtain
      information on water/polymer interactions as a function of pH and polymer
      composition. The experimental results indicated that water interacts with polymer
      chains mainly via hydrogen bonding to carboxylate groups and via proton exchange
      with amino groups. The introduction of agmatine in the polymer disfavors
      water/polymer interactions possibly because of polymer structural changes and
      competing electrostatic interactions with carboxylate groups.

PMID- 19154128
TI  - Computer simulation of the epitaxy of surfactant-templated inorganic
      nanomaterials on patterned surfaces.
AB  - For a surfactant-inorganic-water system, we study systemically the epitaxy
      process of the surfactant-templated inorganic nanomaterial on a patterned surface
      with a lattice Monte Carlo method. It is found that by using ring-patterned
      substrate as a template, vertically oriented inorganic material may be formed
      through the nanometer-scale epitaxy. For all the cases studied in this work, a
      hemicylinder initially formed on the ring pattern behaves as nucleation sites for
      the following growth process. Different parameters, such as surfactant
      architecture, bulk surfactant concentration, fraction of inorganic component, and
      pattern size, are found to affect the epitaxial growth process of the inorganic
      nanomaterial. The change of surfactant architecture alters the structure of
      formed aggregates significantly, thus affecting the epitaxial growth. For the
      effects of surfactant concentration, it is found that there exists a critical
      value. If and only if the bulk surfactant concentration is higher than the
      critical value is the epitaxial growth of inorganic material nucleated from the
      patterned substrate possible. For the effects of the fraction of the inorganic
      component, simulation results indicate that there also exists a volume fraction
      above which the nanomaterial growth is dominated by macrophase separation but not
      templated by the substrate pattern. The geometry of the chemical modification of
      the surface also shows significant effects on the nanometer-scale epitaxy,
      depending on whether its sizes are commensurate with the morphology of the formed
      inorganic nanomaterials or not.

PMID- 19154129
TI  - Ti(III)-promoted radical cyclization of epoxy enones. Total synthesis of (+)
      paeonisuffrone.
AB  - The total synthesis of (+)-paeonisuffrone starting from (+)-10-hydroxycarvone is
      described. The key step of our synthetic strategy is a titanium-catalyzed
      stereoselective cyclization initiated by epoxide opening through electron
      transfer. This reaction stereoselectively affords the highly oxygenated pinane
      skeleton present in the target molecule and opens a new and effective approach to
      the synthesis of the complex, biologically active terpenoids isolated from the
      roots of the Chinese paeony (Paeonia albiflora Pallas and Paeonia suffruticosa
      Andrews).

PMID- 19154132
TI  - Dynamic dielectric response of concentrated colloidal dispersions: comparison
      between theory and experiment.
AB  - The cell-model electrokinetic theory of Ahualli et al. Langmuir 2006, 22, 7041;
      Ahualli et al. J. Colloid Interface Sci. 2007, 309, 342; and Bradshaw-Hajek et
      al. Langmuir 2008, 24, 4512 is applied to a dense suspension of charged spherical
      particles, to exhibit the system's dielectric response to an applied electric
      field as a function of solids volume fraction. The model's predictions of
      effective permittivity and complex conductivity are favorably compared with
      published theoretical calculations and experimental measurements on dense
      colloidal systems. Physical factors governing the volume fraction dependence of
      the dielectric response are discussed.

PMID- 19154130
TI  - Synthesis of bicyclic 2'-deoxynucleosides with alpha-L-ribo- and beta-D-xylo
      configurations and restricted S- and N-type conformations.
AB  - Two bicyclic 2'-deoxynucleoside analogues are synthesized in 12 steps each from
      thymidine. With a six-membered ring fused to the C3'-C4' bond and an alpha-L-ribo
      and a beta-D-xylo-configuration, these are conformationally restricted in an S-
      and an N-type conformation, respectively. The constitutions were proven by X-ray
      crystallography. The beta-D-xylo-configured analogue is successfully converted to
      a 3'-phosphoramidite and incorporated into oligodeoxynucleotides, which are found
      to hybridize to DNA and RNA complements with decreased affinity.

PMID- 19154131
TI  - A general, efficient, and functional-group-tolerant catalyst system for the
      palladium-catalyzed thioetherification of aryl bromides and iodides.
AB  - The cross-coupling reaction of aryl bromides and iodides with aliphatic and
      aromatic thiols catalyzed by palladium complexes of the bisphosphine ligand CyPF
      tBu (1) is reported. Reactions occur in excellent yields, broad scope, high
      tolerance of functional groups, and with turnover numbers that exceed those of
      previous catalysts by 2 or 3 orders of magnitude. These couplings of bromo- and
      iodoarenes are more efficient than the corresponding reactions of chloroarenes
      and could be conducted with less catalyst loading and/or milder reaction
      conditions. Consequently, limitations regarding scope and functional group
      tolerance previously reported in the coupling of aryl chlorides are now overcome.

PMID- 19154133
TI  - Factors that affect the degree of twist in beta-sheet structures: a molecular
      dynamics simulation study of a cross-beta filament of the GNNQQNY peptide.
AB  - By exploiting the recent availability of the crystal structure of a cross-beta
      filament of the GNNQQNY peptide fragment of the yeast prion protein Sup35,
      possible factors affecting the twisting of beta-sheets structures have been
      analyzed. The advantage of this system is that it is composed entirely of beta
      sheet and thus free of potential ambiguities present in systems studied
      previously. In the crystal the cross-beta filament consists of antiparallel beta
      sheets formed by parallel and in register peptides lying perpendicular to the
      long axis of the filament. The results of a series of molecular dynamics
      simulations performed under different conditions indicate that in the absence of
      crystal packing interactions there is no free energy barrier against twisting for
      the cross-beta filament found planar in the crystal. More specifically, we find
      that there is only a small change in enthalpy (<3 kJ mol(-1) per residue) for
      twists in the range 0-12 degrees with the planar form (in the crystal
      environment) being enthalpically stabilized. In contrast, entropic contributions,
      in particular those associated with an increase in backbone dynamics upon
      twisting, stabilize the twisted form. The degree of twist was found to vary
      depending on the environmental conditions as the result from an apparent subtle
      interplay of multiple small contributions. These observations are consistent with
      the different degrees of twist observed in beta-sheets both in native protein
      structures and amyloid fibrils.

PMID- 19154135
TI  - Role of surfactant in the stability of liquid crystal-based nanocolloids.
AB  - We examine the dependence of liquid crystalline nanocolloid formation and
      stability on surfactant. Nanocolloids composed of polymerizable liquid crystal
      mesogens and cross-linking agents and capped with either ionic or nonionic
      surfactants are prepared via the miniemulsion technique. Colloids synthesized
      with anionic surfactant were stable and displayed 2D hexagonal packing when
      deposited via slow vertical pulling of the silicon substrate from an aqueous
      suspension. Liquid crystal nanocolloids stabilized with the nonionic, polar
      polymer polyvinyl alcohol (PVA) were stable in aqueous environments but coalesced
      upon drying to form relatively large, well-defined crystal-like structures with
      uniform birefringence. SEM images reveal that the coalesced structures have
      mesalike features. Polarized light, atomic force, and polarized Raman microscopy
      of these structures indicate that the liquid crystal molecules are arranged with
      their long molecular axis slightly tilted with respect to the surface normal. A
      mechanism is proposed to explain the formation of the mesalike structures from
      the nanocolloids. These studies provide fundamental insight into the
      incorporation and stabilization of polymerizable liquid crystal molecules into
      nanovolumes and open up opportunities for the incorporation of functionality and
      anisotropy into isotropically shaped nanocolloids.

PMID- 19154136
TI  - Solvent dependent optical switching in carbazole-based fluorescent nanoparticles.
AB  - Suitably substituted ethynylphenyl carbazoles (PBM and PPM) form stable
      fluorescent organic nanoparticles. The emission of the nanoparticles can be
      reversibly switched on/off in the blue-green and orange-red regions by a change
      in the ratio of the tetrahydrofuran/water system used in their preparation. The
      size of the nanoparticles was found to be dependent on the solvent ratio, and the
      emissions were significantly red-shifted compared to those of dilute solutions of
      PBM and PPM in tetrahydrofuran. This is attributed to the formation of
      intermolecular charge transfer complexes in the nanoparticle state. The
      application of the nanoparticles as a chemical vapor sensor has been suggested.

PMID- 19154137
TI  - Silver cluster chromophores for absorption enhancement of peptides.
AB  - We present a theoretical study of the structural and optical properties of
      tripeptide-silver cluster hybrid systems which shows that silver clusters induce
      significant absorption enhancement in the spectral region between 225 and 350 nm
      with respect to the pure peptide. This allows the use of clusters as chromophores
      for absorption enhancement of peptides and proteins and offers a potential for
      different applications in biosensing. Furthermore, we demonstrate that cluster
      binding can change the conformational preference for the secondary structure type
      leading possibly to new functional properties.

PMID- 19154134
TI  - Analysis of the structural determinants underlying discrimination between
      substrate and solvent in beta-phosphoglucomutase catalysis.
AB  - Tauhe beta-phosphoglucomutase (beta-PGM) of the haloacid dehalogenase enzyme
      superfamily (HADSF) catalyzes the conversion of beta-glucose 1-phosphate
      (betaG1P) to glucose 6-phosphate (G6P) using Asp8 of the core domain active site
      to mediate phosphoryl transfer from beta-glucose 1,6-(bis)phosphate
      (betaG1,6bisP) to betaG1P. Herein, we explore the mechanism by which hydrolysis
      of the beta-PGM phospho-Asp8 is avoided during the time that the active site must
      remain open to solvent to allow the exchange of the bound product G6P with the
      substrate betaG1P. On the basis of structural information, a model of catalysis
      is proposed in which the general acid/base (Asp10) side chain moves from a
      position where it forms a hydrogen bond to the Thr16-Ala17 portion of the domain
      domain linker to a functional position where it forms a hydrogen bond to the
      substrate leaving group O and a His20-Lys76 pair of the cap domain. This
      repositioning of the general acid/base within the core domain active site is
      coordinated with substrate-induced closure of the cap domain over the core
      domain. The model predicts that Asp10 is required for general acid/base catalysis
      and for stabilization of the enzyme in the cap-closed conformation. It also
      predicts that hinge residue Thr16 plays a key role in productive domain-domain
      association, that hydrogen bond interaction with the Thr16 backbone amide NH
      group is required to prevent phospho-Asp8 hydrolysis in the cap-open
      conformation, and that the His20-Lys76 pair plays an important role in substrate
      induced cap closure. The model is examined via kinetic analyses of Asp10, Thr16,
      His20, and Lys76 site-directed mutants. Replacement of Asp10 with Ala, Ser, Cys,
      Asn, or Glu resulted in no observable activity. The kinetic consequences of the
      replacement of linker residue Thr16 with Pro include a reduced rate of Asp8
      phosphorylation by betaG1,6bisP, a reduced rate of cycling of the phosphorylated
      enzyme to convert betaG1P to G6P, and an enhanced rate of phosphoryl transfer
      from phospho-Asp8 to water. The X-ray crystal structure of the T16P mutant at 2.7
      A resolution provides a snapshot of the enzyme in an unnatural cap-open
      conformation where the Asp10 side chain is located in the core domain active
      site. The His20 and Lys76 site-directed mutants exhibit reduced activity in
      catalysis of the Asp8-mediated phosphoryl transfer between betaG1,6bisP and
      betaG1P but no reduction in the rate of phospho-Asp8 hydrolysis. Taken together,
      the results support a substrate induced-fit model of catalysis in which betaG1P
      binding to the core domain facilitates recruitment of the general acid/base Asp10
      to the catalytic site and induces cap closure.

PMID- 19154139
TI  - Development and etiology of disruptive and delinquent behavior.
AB  - This review examines the development and etiology of disruptive behavior
      [symptoms of oppositional defiant disorder (ODD), conduct disorder (CD), and
      psychopathic features] and delinquency (particularly violence). We address
      selected key developmental issues, including (a) to what extent negative
      emotional ODD symptoms are associated with later internalizing disorders, (b)
      whether psychopathic features provide added predictive utility beyond traditional
      disruptive behaviors, and (c) the role of oppositional behavior and conduct
      problems in the development of violence. This review also focuses on the causes
      of ODD, CD, psychopathic features, and delinquency and explores the extent to
      which the causes of disruptive and delinquent behavior are the same. We examine
      the degree to which risk and promotive factors change with age and whether
      promotive factors buffer the impact of risk factors. Finally, we explore the
      question of whether there are developmental shifts in children's exposure to risk
      and promotive factors.

PMID- 19154140
TI  - Relaxation dynamics of naphthalene and 1-aminonaphthalene in superexcited states.
AB  - The relaxation dynamics of naphthalene (NPH) and 1-aminonaphthalene (AMN) in
      superexcited (SE) states has been investigated by pump-probe femtosecond
      ionization. SE states were produced by two-photon resonant absorption via S1 and
      S2 states and their time evolution probed by ionization with 800 nm light pulses.
      A fine-tuning of the pump and probe laser intensities permits us to separate the
      dynamics of the SE states from that of the S1/S2 intermediate states. SE state
      relaxation pathways were investigated in the channels of the parent and the major
      fragment ions. The lifetimes of two relaxation processes were derived from the
      exponential fit and found to be in the femtosecond and the picosecond time
      scales. The fast component is attributed to internal conversion (IC) from the SE
      states to the Rydberg states, whereas the slow one, only observed in the fragment
      transients, is assigned to fragmentation of the relaxed neutral molecules. The
      study sheds light on the significant role of SE states dynamics in pump-probe
      ionization experiments.

PMID- 19154138
TI  - The proline-rich N-terminal sequence of calcineurin Abeta determines substrate
      binding.
AB  - Three different genes of catalytic subunit A of the Ca(2+)-dependent
      serine/threonine protein phosphatase calcineurin (CaN) are encoded in the human
      genome forming heterodimers with regulatory subunit B. Even though physiological
      roles of CaN have been investigated extensively, less is known about the specific
      functions of the different catalytic isoforms. In this study, all human CaN
      holoenzymes containing either the alpha, beta, or gamma isoform of the catalytic
      subunit (CaN alpha, beta, or gamma, respectively) were expressed for the first
      time. Comparative kinetic analysis of the dephosphorylation of five specific CaN
      substrates provided evidence that the distinct isoforms of the catalytic subunit
      confer substrate specificities to the holoenzymes. CaN alpha dephosphorylates the
      transcription factor Elk-1 with 7- and 2-fold higher catalytic efficiencies than
      the beta and gamma isoforms, respectively. CaN gamma exhibits the highest
      k(cat)/K(m) value for DARPP-32, whereas the catalytic efficiencies for the
      dephosphorylation of NFAT and RII peptide were 3- and 5-fold lower, respectively,
      when compared with the other isoforms. Elk-1 and NFAT reporter gene activity
      measurements revealed even more pronounced substrate preferences of CaNA
      isoforms. Moreover, kinetic analysis demonstrated that CaN beta exhibits for all
      tested protein substrates the lowest K(m) values. Enzymatic characterization of
      the CaN beta(P14G/P18G) variant as well as the N-terminal truncated form CaN
      beta(22-524) revealed that the proline-rich sequence of CaN beta is involved in
      substrate recognition. CaN beta(22-524) exhibits an at least 4-fold decreased
      substrate affinity and a 5-fold increased turnover number. Since this study
      demonstrates that all CaN isoforms display the same cytoplasmic subcellular
      distribution and are expressed in each tested cell line, differences in substrate
      specificities may determine specific physiological functions of the distinct
      isoforms.

PMID- 19154141
TI  - Control over the structural and optical features of nanoparticle-based one
      dimensional photonic crystals.
AB  - Herein we present a detailed analysis of the effect of the spin-coating protocol
      over the optical properties of nanoparticle-based one-dimensional photonic
      crystals. Based on these results, we provide a reliable synthetic route to attain
      high-quality porous multilayers in which the effect of imperfections is minimized
      and whose Bragg diffraction can be precisely tuned over the entire visible and
      near-infrared spectrum. We present a systematic study of the effect of the
      acceleration ramp and final rotation speed over the structural and optical
      quality of these materials. This allows us to relate the structural variations
      observed with the different relative importance of fluid flow and solvent
      evaporation on the thinning of each layer in the stack for the different
      deposition conditions employed.

PMID- 19154142
TI  - Metal-organic polyhedron based on a Cu(II) paddle-wheel secondary building unit
      at the truncated octahedron corners.
AB  - A metal-organic polyhedron of truncated octahedral geometry augmented with a C(4)
      symmetric square-planar Cu(II) paddle-wheel node as a secondary building unit can
      be prepared using a C(3)-symmetric ligand that occupies the face of the
      octahedral cage, where the three phenyl groups containing a m-carboxylate group
      in the ligand provide the necessary curvature to form the finite octahedral cage.

PMID- 19154143
TI  - Sport psychology.

PMID- 19154144
TI  - Effect of chain length on the photophysical properties of pyrene-based molecules
      substituted with extended chains.
AB  - The important role played by organic conjugated compounds in the fields of
      electronics and optoelectronics has led to a vast field of research concerned
      with synthesizing various complex structures where pi-pi stacking plays a vital
      role. Pyrene-based molecules are examples of compounds which allow efficient
      charge transfer through pi-pi molecular stacking. Photophysical studies of such
      compounds have shown similar behavior as that of pyrene, even though they bear
      two additional conjugated rings and four long alkyl chains. Chain length may have
      played an effective role in influencing the pi-pi molecular stacking of such
      molecules. In continuation of our earlier work (Moustafa, R. M.; Degheili, J. A.;
      Patra, D.; Kaafarani, B. R. J. Phys. Chem. A 2008, 113, 1235-1243), we hereby
      synthesize and investigate the role of the chain lengths on the photophysical
      aspects of 2,11-di-tert-butyl-6,7,15,16-tetrakis(alkoxy/alkythio)quinoxaline
      [2',3':9,10]phenanthro[4,5-abc]phenazine, TQPP-[t-Bu](2)-[XR](4) (X = O, S; R =
      C(n)H(2n+1)). Various photophysical parameters such as Stokes shift, fluorescence
      lifetime, fluorescence quantum yield, and radiative and nonradiative rate
      constants are evaluated for TQPP-[t-Bu](2)-[OR](4) and TQPP-[t-Bu](2)-[SR](4) in
      tetrahydrofuran. The variation of the Stokes shift, fluorescence quantum yield,
      and lifetime are also correlated with the number of carbons in the alkyl chain R
      for TQPP-[t-Bu](2)-[OR](4) and TQPP-[t-Bu](2)-[SR](4).

PMID- 19154145
TI  - Synthesis and detailed photophysical studies of pyrene-based molecules
      substituted with extended chains.
AB  - Applications of conjugated organic compounds in the field of electronics and
      optoelectronics and of pyrene derivatives as fluorescent probes are well
      established. The synthesis of the novel pyrene-based 2,11-di-tert-butyl-6,7,15,16
      tetrakis(alkoxy/alkythio)quinoxaline[2',3':9,10]phenanthro[4,5-abc]phenazine,
      TQPP-[t-Bu](2)-[XR](4) (X = O, S; R = C(n)H(2n+1)), is reported along with an in
      depth spectroscopic characterization and evaluation of their photophysical
      properties. Despite their larger core size, the reported TQPP materials showed
      similar fluorescence behavior to that of pyrene itself, with no significant shift
      in their fluorescence peak. The fluorescence spectra showed peaks corresponding
      to the monomer and to the excimer. Even though these TQPP compounds showed poor
      solubility in various solvents, their solvatochromism could be investigated in
      different solvents ranging from polar solvents such as methanol to nonpolar
      solvents such as cyclohexane; Stokes shifts, fluorescence lifetimes, fluorescence
      quantum yields, as well as radiative and nonradiative rate constants are
      determined for four of these TQPP materials in various solvents. Quantum yields
      were found to be low for these TQPP compounds in solvents such as tetrahydrofuran
      (THF), whereas they were relatively higher in cyclohexane and dioxane. Monomer to
      excimer intensity ratio versus gross solvent scale (E(T)30) and orientation
      polarizabilty (Delta f) were correlated. Although TQPP-[t-Bu](2)-[XR](4)
      displayed similar fluorescent emission and excitation behavior as that of pyrene,
      a relatively smaller lifetime was observed for these compounds compared to that
      of pyrene.

PMID- 19154146
TI  - Design of selective neuronal nitric oxide synthase inhibitors for the prevention
      and treatment of neurodegenerative diseases.
AB  - Nitric oxide (NO), which is produced from L-arginine by the nitric oxide synthase
      (NOS) family of enzymes, is an important second-messenger molecule that regulates
      several physiological functions. In endothelial cells, it relaxes smooth muscle,
      which decreases blood pressure. Macrophage cells produce NO as an immune defense
      system to destroy pathogens and microorganisms. In neuronal cells, NO controls
      the release of neurotransmitters and is involved in synaptogenesis, synaptic
      plasticity, memory function, and neuroendocrine secretion. NO is a free radical
      that is commonly thought to contribute to oxidative damage and molecule and
      tissue destruction, and thus it is somewhat surprising that it has so many
      significant beneficial physiological effects. However, the cell is generally
      protected from NO's toxic effects, except under certain pathological conditions
      in which excessive NO is produced. In that case, tissue damage and oxidative
      stress can result, leading to a wide variety of diseases, including rheumatoid
      arthritis, Alzheimer's disease, and Parkinson's disease, among others. In this
      Account, we describe research aimed at identifying small molecules that can
      selectively inhibit only the neuronal isozyme of NOS, nNOS. By targeting only
      nNOS, we attained the beneficial effects of lowering excess NO in the brain
      without the detrimental effects of inhibition of the two isozymes found elsewhere
      in the body (eNOS and iNOS). Initially, in pursuit of this goal, we sought to
      identify differences in the second sphere of amino acids in the active site of
      the isozymes. From this study, the first class of dual nNOS-selective inhibitors
      was identified. The moieties important for selectivity in the best lead compound
      were determined by structure modification. Enhancement provided highly potent,
      nNOS-selective dipeptide amides and peptidomimetics, which were active in a
      rabbit model for fetal neurodegeneration. Crystal structures of these compounds
      bound to NOS isozymes showed a one-amino-acid difference between nNOS and eNOS in
      the second sphere of amino acids; this was the difference that we were searching
      for from the beginning of this project. With the aid of these crystal structures,
      we developed a new fragment-based de novo design method called "fragment
      hopping", which allowed the design of a new class of nonpeptide nNOS-selective
      inhibitors. These compounds were modified to give low nanomolar, highly dual
      selective nNOS inhibitors, which we recently showed are active in a rabbit model
      for the prevention of neurobehavioral symptoms of cerebral palsy. These compounds
      could also have general application in other neurodegenerative diseases for which
      excess NO is responsible.

PMID- 19154147
TI  - Calorimetric evidence for two distinct molecular packing arrangements in stable
      glasses of indomethacin.
AB  - Indomethacin glasses of varying stabilities were prepared by physical vapor
      deposition onto substrates at 265 K. Enthalpy relaxation and the mobility onset
      temperature were assessed with differential scanning calorimetry (DSC). Quasi
      isothermal temperature-modulated DSC was used to measure the reversing heat
      capacity during annealing above the glass transition temperature Tg. At
      deposition rates near 8 A/s, scanning DSC shows two enthalpy relaxation peaks and
      quasi-isothermal DSC shows a two-step change in the reversing heat capacity. We
      attribute these features to two distinct local packing structures in the vapor
      deposited glass, and this interpretation is supported by the strong correlation
      between the two calorimetric signatures of the glass to liquid transformation. At
      lower deposition rates, a larger fraction of the sample is prepared in the more
      stable local packing. The transformation of the vapor-deposited glasses into the
      supercooled liquid above Tg is exceedingly slow, as much as 4500 times slower
      than the structural relaxation time of the liquid.

PMID- 19154149
TI  - Free-radical-induced oxidative and reductive degradation of fibrate
      pharmaceuticals: kinetic studies and degradation mechanisms.
AB  - The presence of pharmaceutically active compounds (PhACs) in aquatic systems is
      an emerging environmental issue and poses a potential threat to ecosystems and
      human health. Unfortunately, current water treatment techniques do not
      efficiently remove all of the PhACs, which results in the occurrence of such
      compounds in surface and ground waters. Advanced oxidation/reduction processes
      (AO/RPs) which utilize free radical reactions to directly degrade chemical
      contaminants are alternatives to traditional water treatment methods. This study
      reports the absolute bimolecular reaction rate constants for three pharmaceutical
      compounds (fibrates), clofibric acid, bezafibrate, and gemfibrozil, with the
      hydroxyl radical (*OH) and hydrated electron (e(-)(aq)). The bimolecular reaction
      rate constants for *OH were (6.98 +/- 0.12) x 10(9), (8.00 +/- 0.22) x 10(9), and
      (10.0 +/- 0.6) x 10(9), and for e(-)(aq) were (6.59 +/- 0.43) x 10(8), (112 +/-
      3) x 10(8), and (6.26 +/- 0.58) x 10(8), for clofibric acid, bezafibrate, and
      gemfibrozil, respectively. Transient spectra were obtained for the intermediate
      radicals produced by the hydroxyl radical reactions. In addition, preliminary
      degradation mechanisms and major products were elucidated using (137)Cs gamma
      irradiation and LC-MS. These data are required for evaluating the potential use
      of AO/RPs for the destruction of these compounds in treating water for various
      purposes.

PMID- 19154151
TI  - ILPR G-quadruplexes formed in seconds demonstrate high mechanical stabilities.
AB  - The insulin linked polymorphism region (ILPR) is known to regulate transcription
      of the gene coding for insulin. The ILPR has guanine rich segments, suggesting
      that G quadruplexes may be responsible for this regulatory role. Using mechanical
      unfolding in a laser tweezers instrument and circular dichroism (CD)
      spectroscopy, we provide compelling evidence that highly stable parallel and
      antiparallel G quadruplex structures coexist in the predominant ILPR sequence of
      (ACAGGGGTGTGGGG)(2) at a physiologically relevant concentration of 100 mM KCl.
      Experiments at the single molecular level have shown that unfolding forces for
      parallel and antiparallel structures (F(unfold): 22.6 vs 36.9 pN, respectively)
      are higher than the stall forces of enzymes having helicase activities. From a
      mechanical perspective alone, these data support the hypothesis that G
      quadruplexes may cause replication slippage by blocking replication process.
      Using the unique combination of the rupture force and the contour length measured
      by laser tweezers, the simultaneous determination of probable parallel and
      antiparallel G quadruplex structures in a solution mixture has been achieved.
      Jarzynski's equality analysis has revealed that the antiparallel G quadruplex is
      thermodynamically more stable than the parallel conformer (DeltaG (unfold): 23 vs
      14 kcal/mol, respectively). On the other hand, kinetic measurements have
      indicated that both parallel and antiparallel structures fold rather rapidly
      (k(fold): 0.4 vs 0.3 s(-1), respectively), suggesting that they may be
      kinetically accessible for gene control. This work provides an unprecedented
      mechanical perspective on G quadruplex stability, presenting a unique opportunity
      to predict the functional consequence when motor enzymes encounter such
      structures.

PMID- 19154150
TI  - Design, synthesis, and evaluation of oxygen-containing macrocyclic
      peptidomimetics as inhibitors of HCV NS3 protease.
AB  - HCV infection is considered a silent epidemic because most people infected do not
      develop acute symptoms. Instead, the disease progresses to a chronic state
      leading to cirrhosis and hepatocarcinoma. Novel therapies are needed to combat
      this major health threat. The HCV NS3 serine protease has been the target of
      continuous investigation because of its pivotal role in viral replication.
      Herein, we present the P1-P3 macrocyclization approach followed for
      identification of HCV NS3 inhibitors as potential backup candidates to our first
      generation drug candidate, Sch 503034 (1). Different P1-P3 linkers were
      investigated to identify novel macrocyclic scaffolds. SAR exploration of P3-caps
      in the macrocyclic cores allowed the identification of l-serine derived
      macrocycle 32 (Ki* = 3 nM, EC90 = 30 nM) and allo-threonine derived macrocycle 36
      (Ki* = 3 nM, EC90 = 30 nM) as potent HCV NS3 protease inhibitors.

PMID- 19154152
TI  - Impact of thermal and nonthermal processing technologies on unfermented apple
      cider aroma volatiles.
AB  - Aroma composition and microbial quality of identical lots of apple cider treated
      by pulsed electric field (PEF), ultraviolet irradiation (UV), or thermal
      pasteurization stored at 4 degrees C were compared at 0 and 4 weeks. Conditions
      were optimized to achieve identical 5 log reductions in Escherichia coli K12 for
      each treatment. PEF and thermal pasteurization maintained acceptable microbial
      quality for 4 weeks, but UV samples fermented after 2 weeks. Twenty-eight
      volatiles were quantified using gas chromatography-mass spectrometry (GC-MS) and
      odor activity values (OAV) determined. OAVs of 69:hexyl acetate, 41:hexanal, 25:2
      methylbutyl acetate, 23:2-methyl ethyl butyrate, and 14:2-(E)-hexenal were
      observed for the control cider. Significant differences (p < 0.05) in the levels
      of these odorants were observed between treated apple ciders only after 4 weeks
      of storage. Thermal samples lost 30% of the major ester and aldehyde volatiles
      during storage with significant decreases (p < 0.05) in butyl acetate, 2
      methylbutyl acetate, hexanal, and 2-(E)-hexenal. In UV cider, hexanal and 2-(E)
      hexenal were completely lost after 4 weeks of storage. Microbial spoilage in UV
      cider after 4 weeks of storage was chemically confirmed by the detection of the
      microbial metabolite 1,3-pentadiene. PEF cider lost <2% of its total ester and
      aldehydes after 4 weeks of storage and was preferred by 91% of the sensory panel
      over thermally treated cider.

PMID- 19154153
TI  - Overview of the chemistry of 2-thiazolines.

PMID- 19154154
TI  - The domino multicomponent allylation reaction for the stereoselective synthesis
      of homoallylic alcohols.
AB  - Stereoselective allylations of carbonyl compounds such as aldehydes and ketones
      are useful but challenging reactions in organic chemistry. The resulting chiral
      secondary and tertiary homoallylic alcohols or ethers are valuable building
      blocks in the synthesis of biologically active natural compounds and
      pharmaceuticals. Although researchers have developed several methods for the
      facially selective allylation of aldehydes, the stereoselective allylation of
      ketones still poses a severe problem. We have developed a highly
      diastereoselective domino multicomponent allylation reaction of a ketone and
      allyltrimethyl silane using the trimethylsilyl ether of a norpseudoephedrine or
      mandelic acid derivative as an auxiliary with a diastereoselectivity of up to
      98:2. The reaction is performed at -78 degrees C in the presence of a catalytic
      amount of trifluoromethanesulfonic acid and leads to the corresponding tertiary
      ethers. The procedure can also be used for the allylation of aliphatic aldehydes
      with a diastereomeric ratio >99:1. Ketones give the 4,1'-syn product while the
      aldehydes give the reversed selectivity to yield a 4,1'-anti product. In
      addition, the reaction of gamma-substituted allyl silanes with ketones yields a
      product with two stereogenic centers and an anti diastereoselectivity of >99:1.
      The homoallylic ethers formed in the domino multicomponent process can be used in
      further synthetic transformations: the auxiliary can serve as a protecting group
      or can be cleaved reductively to give the corresponding homoallylic alcohols.
      Based on a number of both experimental and theoretical studies of the reaction
      mechanism, we conclude that an intermediate oxocarbenium ion is formed in the
      reaction of ketones. The oxocarbenium ion is attacked by the allyl silane during
      the stereogenic step. Using density functional theory methods, we could trace the
      observed stereoselectivity phenomena back to open transition states (TSs) where
      there is no interaction between the silane's trimethylsilyl group and the former
      carbonyl oxygen. On the contrary, the reaction with aldehydes forms an
      intermediate oxazolidinium salt, which explains the opposite selectivity. We have
      used the new allylation procedure in several total syntheses of natural products
      such as vitamin E, (+)-hydroxymyoporone, 5,6-dihydrocineromycin B, and
      polyoxygenated cembrenes.

PMID- 19154156
TI  - Surface-anchoring of spontaneously dimerized epidermal growth factor for highly
      selective expansion of neural stem cells.
AB  - To develop culture substrates for use in selective expansion of neural stem cells
      (NSCs), epidermal growth factor (EGF)-containing chimeric proteins were designed
      and synthesized by means of recombinant DNA technology. The chimeric proteins
      consisted of three components including an EGF domain, an alpha-helical
      oligopeptide, and a hexahistidine sequence. Two different alpha-helical
      oligopeptides were separately incorporated into chimeric proteins. Structural
      analyses by native gel electrophoresis and circular dichroism spectroscopy
      revealed that the heterodimer of these proteins was spontaneously formed through
      coiled-coil association of the alpha-helical oligopeptides. The monomeric and
      dimeric forms of these chimeric proteins were immobilized to the glass-based
      substrate via coordinate bonding between the hexahistidine and Ni(II) ions fixed
      on a substrate. The results of cell culture assays with NSCs showed that cells
      proliferated most rapidly and selectively on a substrate with the surface
      anchored EGF dimer. The rate of cell proliferation on the surface with dimeric
      EGF was 1.3-2.0 times higher on the surfaces with monomeric EGF. In addition, the
      content of stem cells, determined 96 h after cell seeding, was highest on the
      surface with dimeric EGF (98%) among the surfaces studied (90-97% on surfaces
      with monomeric EGF). The observed growth rate and the stem cell content on the
      surface with EGF dimer were far beyond those in the standard neurosphere culture.
      The effect of surface-anchored dimeric EGF may be attributed to the enhanced
      dimerization of EGF-EGF receptor complexes leading to efficient signaling for
      mitogenic activity. We conclude that surface-anchoring of the EGF dimer provides
      an excellent substrate that allows the highly efficient expansion of NSCs.

PMID- 19154158
TI  - Quantification of several 4-alkyl substituted gamma-lactones in Australian wines.
AB  - Stable isotope dilution assays have been developed for gamma-octalactone (1),
      gamma-nonalactone (2), gamma-decalactone (3) and gamma-dodecalactone (4) in both
      white and red wines for the first time. (2)H(7)-analogues of each lactone were
      prepared for use as internal standards via a strategy employing ring-opening,
      esterification and oxidation of the respective starting lactones. The methods
      were shown to be highly accurate and reproducible (R(2) > or = 0.999; SD < or =
      1%). A large selection of Australian wines (n = 178) were analyzed for the
      presence of lactones 1-4. Fifty-eight white wines covering the varieties
      Chardonnay, Riesling, Sauvignon Blanc, Semillon and Viognier, as well as Botrytis
      style wines, were analyzed and showed broadly that gamma-octalactone (1) was the
      most common lactone, being observed above its limit of detection in 28 of the
      wines, followed by gamma-nonalactone (2) in 23 wines. The Botrytis style white
      wines had the highest concentrations of 1 and 2 (maximum concentrations 8.5 and
      59 microg/L respectively). A total of 120 red wines covering the varieties
      Cabernet Sauvignon, Durif, Merlot, Pinot Noir and Shiraz were also studied and
      showed gamma-octalactone (1) and gamma-nonalactone (2) to be the most common
      lactones present, in 56 and 57 of the wines, respectively. gamma-Decalactone (3)
      was observed in only a small number (13) of red wine samples and not at all in
      the white varieties. gamma-Dodecalactone (4) was absent from all 178 samples
      studied. The highest concentrations of lactones 1, 2 and 3 in the red wines were
      4.2, 39.7 and 4.0 microg/L respectively.

PMID- 19154157
TI  - Synthesis and evaluation of multivalent branched HPMA copolymer-Fab' conjugates
      targeted to the B-cell antigen CD20.
AB  - Several drug delivery designs combine synthetic drug carriers with covalently
      conjugated targeting moieties. Such modifications of monoclonal antibodies (mAb),
      or their Fab' fragments, inevitably result in diminished affinity for their
      targeted tissue. In an attempt to overcome this limitation, high molecular
      weight, branched N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers were
      synthesized and conjugated with Fab' fragments of the anti-CD20 antibody, 1F5.
      This produced multivalent conjugates with varying valency (amount of Fab' per
      macromolecule) targeted to the B-cell antigen CD20. Evaluation of a multivalent
      effect was done by determining the apparent K(D) at low concentrations of
      conjugates, the Sips heterogeneity factor, a, and the binding enhancement factors
      of each construct. The results clearly indicated that multivalency could improve
      the affinity of the HPMA copolymer-Fab' conjugates to that of unconjugated mAb.

PMID- 19154159
TI  - Generation of broad specificity antibodies for sulfonamide antibiotics and
      development of an enzyme-linked immunosorbent assay (ELISA) for the analysis of
      milk samples.
AB  - Immunoreagents appropriately produced to detect a wide range of sulfonamide
      antibiotic congeners have been used to develop a highly sensitive enzyme-linked
      immunosorbent assay (ELISA). The selectivity has been achieved by combining
      antibodies raised against 5-[6-(4-aminobenzenesulfonylamino)pyridin-3-yl]-2
      methylpentanoic acid (SA1), covalently coupled to horseshoe crab hemocyanin
      (HCH), and 5-[4-(amino)phenylsulfonamide]-5-oxopentanoic acid (SA2), coupled to
      ovalbumin (OVA), on an indirect ELISA format. The immunizing hapten has been
      designed to address selectivity against the common aminobenzenesulfonylamino
      moieties, using theoretical calculations and molecular modeling tools. Hapten SA1
      has been synthesized in four steps from methyl 5-(4-amino-3-pyridinyl)-2-methyl-4
      pentenoate through a Heck reaction, under Jeffery conditions, to avoid
      introduction of additional epitopes in the linker. The microplate immunoassay
      developed is able to reach the necessary detectability for the determination of
      the sulfonamide antibiotics most frequently used in the veterinary field, in
      compliance with the EC Regulation 2377/90. As an example, the IC(50) and LOD
      values accomplished for sulfapyridine are 2.86 +/- 0.24 and 0.13 +/- 0.03 microg
      L(-1), respectively. Studies performed with different types of milk samples
      demonstrate that direct and accurate measurements can be performed in this type
      of matrix without any previous sample cleanup method.

PMID- 19154160
TI  - Angiotensin I converting enzyme inhibitory peptides from simulated in vitro
      gastrointestinal digestion of cooked eggs.
AB  - Egg proteins are an excellent source of bioactive peptides. The purpose of this
      work was to study the effect of cooking methods on the production of angiotensin
      converting enzyme (ACE) inhibitory peptides. Boiled or fried eggs (in the forms
      of whites, yolks, and whole eggs) were digested by gastrointestinal tract
      proteases at simulated gut conditions. Fried egg digests showed more potent
      activity than those of boiled egg digests; the fried whole egg digest had an
      IC(50) value of 0.009 mg protein/mL. This hydrolysate was further purified by
      cation exchange chromatography and gel filtration chromatography. Seven peptides,
      Val-Asp-Phe (IC(50): 6.59 microM), Leu-Pro-Phe (10.59 microM), Met-Pro-Phe (17.98
      microM), Tyr-Thr-Ala-Gly-Val (23.38 microM), Glu-Arg-Tyr-Pro-Ile (8.76 microM),
      Ile-Pro-Phe (8.78 microM), and Thr-Thr-Ile (24.94 microM), were identified by
      liquid chromatography-mass spectrometry (LC-MS/MS), and their IC(50) values were
      predicted by using our previously reported structure and activity models. The
      presence of several tripeptides from in vitro simulated gastrointestinal egg
      digest indicates that these peptides may be absorbed into the body and exert an
      in vivo antihypertensive activity, although in vivo study is needed to confirm
      this assumption. Our results showed that in vitro digestion of cooked eggs could
      generate a number of potent ACE inhibitory peptides which may have implications
      for cardiovascular disease prevention, including hypertension.

PMID- 19154161
TI  - Terpenes from Eupatorium adenophorum and their allelopathic effects on
      Arabidopsis seeds germination (dagger).
AB  - The invasive plant Eupatorium adenophorum Spreng. (or Ageratina adenophora
      (Spreng.) King and Robinson) (Compositae) has caused great economic loss in
      China, especially the southwestern region, and is gravely threatening the native
      biodiversity. The aerial part of this plant was phytochemically investigated for
      its allelochemicals. Eleven terpenes (2 monoterpenes and 9 sesquiterpenes) were
      isolated and identified, which include a new monoterpene, (-)-(1R*,2S,*4R*,5S*)
      3,3-dimethyl-5-hydroxybicyclo[2,2,1]hept-2-ylmethanol (1), two new cadinane
      sesquiterpenes, (-)-(5S*,6S*,7S*,9R*,10S*)-7-hydroxy-5,7-epidioxycadinan-3-ene-2
      one (2) and (+)-(5S*,6R*,9R*,10S*)-5,6-dihydroxycadinan-3-ene-2,7-dione (3), and
      eight known terpene compounds (4, 6-12). The new structures were established by
      spectroscopic studies such as 1D- and 2D-NMR and MS analyses. Meanwhile, the
      potential allelopathic effects of these compounds on the Arabidopsis seeds
      germination were tested. Compounds 3 and 7 retarded the Arabidopsis seeds
      germination at 0.5 mM and 1.0 mM concentrations, respectively, while other
      compounds showed no obvious inhibitory effects.

PMID- 19154162
TI  - Simultaneous detection of multifood-borne pathogenic bacteria based on
      functionalized quantum dots coupled with immunomagnetic separation in food
      samples.
AB  - This paper reports a method that simultaneously detects three food-borne
      pathogenic bacteria, Salmonella typhimurium, Shigella flexneri, and Escherichia
      coli O157:H7, via an approach that combines magnetic microparticles for the
      enrichment and antibody-conjugated semiconductor quantum dots (QDs) as
      fluorescence markers. Using the water-in-oil reverse microemulsions method, the
      gamma-Fe(2)O(3) magnetic nanoparticles were coated with silica to empower the
      particles with high dispersibility and broad compatibility to biomacromolecules.
      The magnetic beads were then modified with amino silane, which could immobilize
      antibodies by glutaraldehyde treatment. The immunized magnetic beads and
      pathogenic bacteria formed "bead-cell" complexes in the enrichment procedure. QDs
      with different emission wavelengths (620, 560, and 520 nm) were immobilized with
      anti-S. typhimurium antibody, anti-S. flexneri antibody, and anti-E. coli O157:H7
      antibody, respectively. Fluorescence microscope images and the fluorescence
      intensity of QDs labeled "sandwich" complexes (conjungated with antibodies
      against S. typhimurium, S. flexneri, and E. coli O157:H7, respectively)
      demonstrated that antibody-conjugated QDs could attach to the surface of
      bacterial cells selectively and specifically. In our method, we could detect food
      borne pathogen bacteria in a food matrix at 10(-3) cfu/mL. We determined that a
      high concentration of proteins in food matrix would decrease the sensitivity of
      this method. This method, of which the detection procedures are completed within
      2 h, can be applied to the rapid and cost-effective monitoring of bacterial
      contamination in food samples.

PMID- 19154163
TI  - Changes in volatiles and glycosides during fruit maturation of two contrasted
      tomato ( Solanum lycopersicum ) lines.
AB  - The relationship between fruit maturation and volatile contents was investigated
      in two contrasted Cervil (CER) and Levovil (LEV) tomato ( Solanum lycopersicum )
      lines. As fruits ripened, their volatile contents mainly increased. Although some
      compounds displayed contrasting patterns, overall, volatiles were clearly more
      abundant and conferred stronger aromas to CER than to LEV fruits. This
      intervarietal difference in volatile contents yielding much lower volatile
      contents in LEV was further investigated to determine whether it is due to a
      higher capacity of volatile glycosylation within LEV as compared to CER. Again,
      glycosides mainly increased during fruit maturation and were more abundant within
      CER than within LEV. Overall glycoside findings were indicative of a superior
      capacity to biosynthesize rather than an inferior capacity to glycosylate
      volatiles of CER. Eugenol and 2-methoxyphenol volatiles were exceptional
      compounds as they remained at higher levels in maturing LEV than in CER. 2
      Methylthioacetaldehyde was for the first time identified as putatively related to
      differences of aroma between lines, as it was abundant in Cervil but absent in
      Levovil. Considering the described odor value of these three products, they
      should contribute differently to the particular olfactive features of LEV and CER
      fruits.

PMID- 19154164
TI  - Phenanthrene sorption by fruit cuticles and potato periderm with different
      compositional characteristics.
AB  - Phenanthrene sorption by fruit cuticles (tomato, apple, and grape), potato tuber
      periderm, and their fractions were investigated to elucidate effects of
      compositional characteristics on affinity of plant cuticle (above-ground) and
      periderm (below-ground) with hydrophobic organic contaminants (HOCs). The
      distinct roles of the extractable lipids (waxes), the depolymerizable lipids
      (cutin/suberin), the nonsaponifiable lipids (cutan/suberan) and polysaccharide
      are discussed. The cutin/suberin rather than waxes dominates the sorption
      properties of bulk cuticle/periderm, but the sorption coefficient (K(d)) is
      linearly correlated with the total lipid contents. Polysaccharide plays a
      negative role in HOC sorption due to its obviously poor affinity with HOCs and
      restriction effect on the other powerful sorptive regions in cuticle/periderm.
      The significantly lower sorption of periderm than cuticle is attributed to the
      former having higher polysaccharide and lower depolymerizable lipids. The linear
      correlation of K(d) of bulk cuticle/periderm with polysaccharide content is
      observed for a potential prediction of plant uptake.

PMID- 19154165
TI  - Latency and persistence of diet volatile biomarkers in lamb fats.
AB  - Several studies have shown that volatile compounds are particularly well-suited
      for the authentication lamb diet by gas chromatography-mass spectrometry (GC-MS)
      analysis of adipose tissue. The aim of the present work was to use dynamic
      headspace-GC-MS to study the variations in the amounts of volatile diet tracers
      in perirenal fat (PRF) and caudal subcutaneous fat (CSCF) in lambs (n = 24) that
      were fed with concentrate and then allowed to graze for 0, 17, 51, or 85 days.
      Twenty-six volatile compounds were found to distinguish between the four diets (p
      < 0.05) in both PRF and CSCF. Of these diet tracers, 16 were found to be related
      to the pasture diet and increased at different rates according to the time spent
      at pasture (latency), while 10 were found in higher amounts in tissues of lambs
      fed with exclusive concentrate and exhibited different rates of clearance
      (persistence). Twenty-four of these discriminant compounds, including alkanes,
      ketones, terpenes, and 2,3-octanedione, were previously stated as pasture diet
      tracers in several earlier studies, suggesting their potential universality. All
      degrees of latency or persistence were exhibited by the pasture and concentrate
      diet tracers, respectively. A principal component analysis performed on ratios of
      selected diet tracers from both adipose tissues evidenced successful
      differentiation of the four feeding situations.

PMID- 19154166
TI  - Moisture and temperature triggered release of a volatile active agent from soy
      protein coated paper: effect of glass transition phenomena on carvacrol diffusion
      coefficient.
AB  - Carvacrol release from SPI-coated papers was evaluated at different relative
      humidities (RH; 60, 80, and 100%) and storage temperatures (5, 20, and 30 degrees
      C). Effective carvacrol diffusivities were determined from experimental release
      kinetics and by using a mathematical model based on Fick's second law. Increasing
      storage temperature and RH lead to an increase of carvacrol diffusivity.
      Depending on the relative humidity, the carvacrol effective diffusivity varied
      from 1.71 x 10(-16) to 138 x 10(-16) m(2)/s at 30 degrees C, from 0.85 x 10(-16)
      to 8.78 x 10(-16) m(2)/s at 20 degrees C, and from 0.11 x 10(-16) to 7.50 x 10(
      16) m(2)/s at 5 degrees C. The combined effect of relative humidity and
      temperature on diffusivity was particularly marked at 30 degrees C and 100% RH.
      The temperature and relative humidity dependence of carvacrol release was related
      to the glass transition phenomenon and its effect on chain protein mobility and
      carvacrol diffusivity.

PMID- 19154167
TI  - Properties of starch subjected to partial gelatinization and beta-amylolysis.
AB  - The overall objective of this research is to understand the impact of partial
      gelatinization and beta-amylase hydrolysis (beta-amylolysis) on the
      physicochemical properties of starch. Three starches (normal corn, waxy corn, and
      wheat) were chosen as test examples and thermally treated at 40% moisture content
      to up to 95 degrees C and then subjected to beta-amylolysis. The enzyme treatment
      resulted in over 10% maltose yield. Subsequent debranching analysis showed the
      production of chain stubs as short as having the degree of polymerization of 2
      and 3, suggesting a thorough beta-amylolysis at certain branch locations. For
      starch samples subjected to partial gelatinization, polarized light microscopy
      shows reduced intensity of birefringence and differential scanning calorimetry
      shows reduced enthalpy change associated with gelatinization. Both indicate the
      reduced chain organization due to the treatment. Further, a substantial
      transformation of initial A-type crystalline structure to B- and V-types upon
      treatments is noticed from X-ray powder diffraction measurements. In addition,
      the rapid viscosity analysis (RVA) indicated a drastic viscosity reduction,
      increased peak temperature, and improved stability of pasting behavior due to
      hydrothermal treatments and beta-amylolysis. Overall, our results point out the
      possibility of obtaining modified starches having desirable stable pasting
      behavior by using a combined partial gelatinization and beta-amylolysis approach.

PMID- 19154168
TI  - Selenium accumulation in different brown rice cultivars and its distribution in
      fractions.
AB  - The goal of this paper was to study the accumulation of selenium (Se) in
      different cultivars of brown rice and its distribution in fractions. The results
      of the study showed that Se content in brown rice increased significantly (P <
      0.01) as the external selenite or selenate concentrations increased from 10 to
      180 micromol/L. In contrast, no significant influence (P > 0.05) on germination
      percentage and growth of sprouts was observed when the supplied Se was lower than
      60 micromol/L. Moreover, selenite was easily transformed into selenoproteins to
      selenate. Based on this, ten brown rice cultivars were compared for Se
      accumulation. Likewise, significant difference (P < 0.01) was found among
      cultivars with respect to the capacity for Se accumulation. To understand the
      distribution of Se in selenized brown rice and its loss during milling, two
      cultivars with relatively higher ability to accumulate Se, namely, Zhendao 8 (Z8)
      and Xieyou 57 (X57), were selected for further study. The results showed that Se
      content was highest in the sprouts and decreased remarkably (P < 0.01) from the
      bran layers to the endosperm. In terms of Se loss during the milling procedure,
      39.02% and 48.46% of Se were lost in Z8 and X57, respectively.

PMID- 19154169
TI  - Prolamin hydrolysis and pentosan solubilization in germinated-rye sourdoughs
      determined by chromatographic and immunological methods.
AB  - The assortment and quality of bakery products designed for celiac patients may be
      improved by designing whole grain ingredients with low residual prolamin
      contents. The main objective of this study was to evaluate the extent of prolamin
      hydrolysis and pentosan solubilization in germinated-rye sourdoughs (GRSDs). Size
      exclusion chromatography analyses, the fate of fluorescent prolamin, and
      immunological analyses determined the extent of prolamin hydrolysis and pentosan
      solubilization. Hydrolysis of rye prolamins was extensive in GRSDs, and according
      to enzyme-linked immunosorbent assay analyses, more than 99.5% of the prolamins
      were hydrolyzed. Pentosan solubilization occurred in native-rye sourdoughs,
      whereas in GRSDs, pentosans were partially hydrolyzed to monosaccharides. Test
      baking showed that the use of GRSD improved the overall quality of oat bread and
      that an estimated daily gluten intake from 100 g of bread would be less than 10
      mg. However, the clinical safety must be assured before making any
      recommendations for celiac patients to use such products.

PMID- 19154170
TI  - Efficient three-photon excited deep blue photoluminescence and lasing of
      diphenylamino and 1,2,4-triazole endcapped oligofluorenes.
AB  - A novel homologues series of diphenylamino and 1,2,4-triazole endcapped pi
      conjugated oligofluorenes has been synthesized using palladium-catalyzed Suzuki
      cross-coupling of 9,9-dibutyl-7-(diphenylamino)-2-fluorenylboronic acid, and
      1,2,4,-triazole-substituted oligofluorenyl halide was used as a key step.
      Efficient two- and three-photon excited photoluminescence and lasing were
      obtained by pumping with near-infrared femto-second lasers. The three-photon
      absorption cross-section enhances significantly up to 2.48 x 10(-78) cm(6) s(2)
      in the femtosecond regime with the length of the conjugation system. The emission
      is in the deep blue region and the best full width half-maximum (fwhm) of the
      three-photon lasing is narrower than 6 nm which is the narrowest ever reported.
      It was also shown that the nonlinear optics (NLO) effect increased parabolically
      with the conjugation length but without changing the emission wavelength. This
      demonstrates that varying the conjugation length is a very effective way to
      tailor an OF-based NLO device for deep blue application. Our findings open a new
      avenue to design highly efficient multiphoton absorption molecules for
      photoluminescence and lasing as well as provide a novel series of organic
      molecules that can be used in NLO applications and fundamental study.

PMID- 19154171
TI  - An approach to thermodynamically controlled supramolecular assembly possessing an
      integral locking mechanism.
AB  - A general approach for thermodynamically controlled molecular assembly employing
      carbonyl addition chemistry is exemplified with a prototypical rotaxane
      synthesis. Recognition-driven assembly of the rotaxane proceeds under conditions
      of mild base catalysis, while subsequent treatment with catalytic acid triggers a
      dehydrative locking mechanism and fixes the evolved molecular architecture in
      place.

PMID- 19154172
TI  - Highly enantio- and diastereoselective one-pot methods for the synthesis of
      halocyclopropyl alcohols.
AB  - The lack of methods for the stereoselective transfer of functionalized carbenoids
      is one of the most significant deficiencies of Simmons-Smith cyclopropanation
      reactions. Outlined herein are one-pot methods for the catalytic asymmetric
      synthesis of halocyclopropyl alcohols with up to four stereogenic centers from
      achiral starting materials. The first method involves asymmetric alkyl addition
      to a conjugated enal to generate an allylic alkoxide followed by tandem
      diastereoselective iodo-, bromo-, or chlorocyclopropanation to furnish
      halocyclopropyl alcohols. Enantioselectivities in these processes range from 89
      99%, and dr's of >20:1 were achieved with all substrates optimized. The second
      method consists of an asymmetric vinylation of a saturated or aromatic aldehyde
      followed by a diastereoselective iodocyclopropanation to produce iodocyclopropyl
      alcohols with enantioselectivities between 86 and 99% and dr's of >20:1. These
      complementary methods enable the efficient synthesis of a variety of
      halocyclopropyl alcohols in one-pot procedures. Preliminary efforts to
      functionalize iodocyclopropanes involve reaction with an excess of LiCu(n-Bu)(2)
      to generate the cyclopropyl cuprate. This intermediate can be quenched with allyl
      bromides to generate the allylated cyclopropyl alcohols without loss of enantio-
      or diastereoselectivity.

PMID- 19154173
TI  - The U=C double bond: synthesis and study of uranium nucleophilic carbene
      complexes.
AB  - Treatment of U(BH(4))(4) with 1 or 3 equiv of Li(2)(SCS) x 1.5 Et(2)O, 1,
      afforded the actinide carbene complexes U(mu-SCS)(3)[U(BH(4))(3)](2) (4) and U(mu
      SCS)(3)[Li(Et(2)O)](2) (6), respectively [SCS = (Ph(2)P = S)(2)C]. In THF,
      complex 4 was transformed into the mononuclear derivative
      (SCS)U(BH(4))(2)(THF)(2) (5). The multiple bond character of the uranium-carbon
      bond was first revealed by the X-ray crystal structures of the three complexes.
      The U=C bond in these complexes present a nucleophilic character, as shown by
      their reaction with a carbonyl derivative. Finally, DFT calculations prove the
      involvement of both 5f and 6d orbitals in both the sigma and the pi U-C bonds.

PMID- 19154174
TI  - The oil-water interface: mapping the solvation potential.
AB  - An ion moving across an oil-water interface experiences strong solvation changes.
      We have directly measured the solvation potential from 0.4 to 4 nm for Cs(+) ions
      approaching the oil-water interface from the oil side ("oil" = 3-methylpentane).
      The interfaces were built at 30 K using molecular beam epitaxy. Ions were
      precisely placed within the film during its growth using a soft-landing ion beam.
      The ion's collective electric field was progressively increased (by adding more
      ions) until it balanced the individual ion's solvation potential slope. As the
      samples were slowly warmed, near 90 K the ions began moving, as measured by a
      Kelvin probe. Their motion precisely determines the local slope of the solvation
      potential, which was integrated to get the potential. The potential is Born-like
      for z > 0.4 nm away from the oil-water interface. Our method could provide
      important tests of theoretical estimates of ion motion at biological interfaces
      and in atmospheric aerosols.

PMID- 19154175
TI  - Structures of silicon cluster cations in the gas phase.
AB  - We present gas-phase infrared spectra for small silicon cluster cations
      possessing between 6 and 21 atoms. Infrared multiple photon dissociation (IR-MPD)
      of these clusters complexed with a xenon atom is employed to obtain their
      vibrational spectra. These vibrational spectra give for the first time
      experimental data capable of distinguishing the exact internal structures of the
      silicon cluster cations. By comparing the experimental spectra with theoretical
      predictions based on density functional theory (DFT), unambiguous structural
      assignments for most of the Si(n)(+) clusters in this size range have been made.
      In particular, for Si(8)(+) an edge-capped pentagonal bypriamid structure,
      hitherto not considered, was assigned. These structural assignments provide
      direct experimental evidence for a cluster growth motif starting with a
      pentagonal bipyramid building block and changing to a trigonal prism for larger
      clusters.

PMID- 19154176
TI  - Probing general acid catalysis in the hammerhead ribozyme.
AB  - Recent crystallographic and computational studies have provided fresh insights
      into the catalytic mechanism of the RNA-cleaving hammerhead ribozyme. Based on
      these findings, specific ribozyme functional groups have been hypothesized to act
      directly as the general acid and base catalysts, although the catalytic role of
      divalent metal cations (M(2+)) remains uncertain. We now report a functional
      characterization of the general acid catalysis mechanism and the role of an M(2+)
      cofactor therein, for the S. mansoni hammerhead (an "extended" hammerhead
      ribozyme). We have compared hammerhead cleavage of substrates with natural (ribo
      phosphodiester) versus bridging-5'-phosphorothioate scissile linkages, in the
      contexts of active site mutations and M(2+) substitution. Cleavage of the natural
      substrate is inhibited by modification of the G8 2'-OH ribozyme residue and
      depends strongly upon the presence and identity of an M(2+) cofactor; in
      contrast, cleavage of the bridging-phosphorothioate substrate is conspicuously
      insensitive to any of these factors. These results imply that (1) both an M(2+)
      cofactor and the G8 2'-OH play crucial roles in hammerhead general acid catalysis
      and (2) the M(2+) cofactor does not contribute to general acid catalysis via
      Lewis acid stabilization of the leaving group. General acid pK(a) perturbation
      was also demonstrated for both M(2+) substitution and G8 2'-OH modification,
      which suggests transition state M(2+) coordination of the G8 2'-OH, to lower its
      pK(a) and improve its ability to transfer a proton to the leaving group. We also
      report a simple method for synthesizing radiolabeled bridging-5'-phosphorothioate
      substrates.

PMID- 19154177
TI  - Electrolyte tuning of surfactant interfacial behavior for enhanced density-based
      separations of single-walled carbon nanotubes.
AB  - We study the interfacial behavior between the straight-chain alkyl surfactant
      sodium dodecyl sulfate (SDS) and single-walled carbon nanotubes (SWNTs) as a
      function of added electrolytes, including NaCl. We observe an increase in
      photoluminescence intensity and narrowing of spectral line widths with
      electrolyte addition, indicating a change in SDS aggregation number that leads to
      a pronounced volume change in the nanotube/SDS composite structure. By tuning the
      interfacial dynamics through NaCl addition and temperature change, we demonstrate
      that this volume change can be used to yield diameter-dependent separation of
      metallic and semiconducting SWNTs, without the use of any additional
      cosurfactant, through density gradient ultracentrifugation. The diameter
      dependent fractionation follows the intrinsic relation expected for the density
      of unfunctionalized nanotubes, indicating a simple amplification of these
      inherent density differences as the mechanism for salt enhanced separations.
      Isolation of enriched metallic and semiconducting fractions further illustrates
      that the surface aggregation characteristics of SDS on metallic SWNTs are
      different from that on the semiconducting chiralities. These experiments
      illustrate the governing behavior of surface phenomena and interfacial forces on
      the diameter-dependent fractionation of SWNTs and point to new routes for
      enhancing existing separations strategies.

PMID- 19154179
TI  - NMR structure determination of a segmentally labeled glycoprotein using in vitro
      glycosylation.
AB  - Although there is great interest in three-dimensional structures of glycoproteins
      and complex oligosaccharides, their structural determination have been hampered
      by inhomogeneous and incomplete glycosylation, poor expression, low tendency to
      crystallize, and severe chemical shift overlap. Using segmental labeling of the
      glycan and the protein component by in vitro glycosylation, we developed a novel
      method of NMR structural determination that overcomes some of these problems.
      Highly homogeneously glycosylated proteins in milligram amounts can be obtained.
      This allowed the determination of the structure of an N-linked glycoprotein from
      Campylobacter jejuni. The glycosylation acceptor site was found to be in a
      flexible loop. The presented methodology extends the observable NOE distance
      limit of oligosaccharides significantly over 4 A, resulting in a high number of
      distance restraints per glycosidic linkage. A well-defined glycan structure was
      obtained.

PMID- 19154178
TI  - Total synthesis and evaluation of iso-duocarmycin SA and iso-yatakemycin.
AB  - The total synthesis and evaluation of iso-duocarmycin SA (5) and iso-yatakemycin
      (6), representing key analogues of the corresponding natural products
      incorporating an isomeric alkylation subunit, are detailed. This pyrrole isomer
      of the natural alkylation subunit displayed an enhanced reaction regioselectivity
      and a 2-fold diminished stability. Although still exceptionally potent, the iso
      duocarmycin SA derivatives and natural product analogues exhibited a
      corresponding approximate 3-5-fold reduction in cytotoxic activity [L1210 IC(50)
      for (+)-iso-duocarmycin SA = 50 pM and for (+)-iso-yatakemycin = 15 pM]
      consistent with their placement on a parabolic relationship correlating activity
      with reactivity. The DNA alkylation selectivity of the resulting key natural
      product analogues was unaltered by the structure modification in spite of the
      minor-groove presentation of a potential H-bond donor. Additionally, a unique
      ortho-spirocyclization with such derivatives was explored via the preparation,
      characterization, and evaluation of 34 that is incapable of the more conventional
      para-spirocyclization. Although 34 proved sufficiently stable for isolation and
      characterization, it displayed little stability in protic solvents (t(1/2) = 0.19
      h at pH 3, t(1/2) = 0.20 h at pH 7), a pH-independent (H(+) independent)
      solvolysis rate profile at pH 3/4-7, and a much reduced cytotoxic potency, but a
      DNA alkylation selectivity and efficiency comparable to those of duocarmycin SA
      and iso-duocarmycin SA. The implications of these observations on the source of
      the DNA alkylation selectivity and catalysis for this class of natural products
      are discussed.

PMID- 19154180
TI  - Developmental brain protein level changes in the C57BL/6J mouse.
AB  - As work on systematic searches for developmentally-regulated proteins is limited,
      whole brains of CL57B/6J mice were taken from day 16 of gestation, at postnatal
      days 7 and 54-58. Proteins were extracted, and analyzed by a gel-based proteomic
      method (ion trap HCT). Antioxidant, cytoskeleton, chaperone, several metabolic
      proteins from different pathways, proteins from the protein synthetic and
      degradation machinery, sirtuin and a mitochondrial inner membrane protein were
      developmentally regulated.

PMID- 19154182
TI  - Crystal structure of rat haem oxygenase-1 in complex with ferrous verdohaem:
      presence of a hydrogen-bond network on the distal side.
AB  - HO (haem oxygenase) catalyses the degradation of haem to biliverdin, CO and
      ferrous iron via three successive oxygenation reactions, i.e. haem to alpha
      hydroxyhaem, alpha-hydroxyhaem to alpha-verdohaem and alpha-verdohaem to ferric
      biliverdin-iron chelate. In the present study, we determined the crystal
      structure of ferrous alpha-verdohaem-rat HO-1 complex at 2.2 A (1 A=0.1 nm)
      resolution. The overall structure of the verdohaem complex was similar to that of
      the haem complex. Water or OH- was co-ordinated to the verdohaem iron as a distal
      ligand. A hydrogen-bond network consisting of water molecules and several amino
      acid residues was observed at the distal side of verdohaem. Such a hydrogen-bond
      network was conserved in the structures of rat HO-1 complexes with haem and with
      the ferric biliverdin-iron chelate. This hydrogen-bond network may act as a
      proton donor to form an activated oxygen intermediate, probably a ferric
      hydroperoxide species, in the degradation of alpha-verdohaem to ferric biliverdin
      iron chelate similar to that seen in the first oxygenation step.

PMID- 19154183
TI  - Role of aryl hydrocarbon receptor in modulation of the expression of the hypoxia
      marker carbonic anhydrase IX.
AB  - Tumour-associated expression of CA IX (carbonic anhydrase IX) is to a major
      extent regulated by HIF-1 (hypoxia-inducible factor-1) which is important for
      transcriptional activation and consists of the oxygen-regulated subunit HIF
      1alpha and the partner factor ARNT [AhR (aryl hydrocarbon receptor) nuclear
      translocator]. We have previously observed that HIF-1alpha competes with the AhR
      for interaction with ARNT under conditions when both conditionally regulated
      factors are activated. We have therefore investigated whether TCDD (2,3,7,8
      tetrachlorodibenzo-p-dioxin)-induced activation of the AhR pathway might
      interfere with CA IX expression. The results from the present study suggest that
      TCDD treatment reduces hypoxic induction of both CA IX mRNA and protein
      expression. Moreover, the transcriptional activity of the CA9 promoter was
      significantly reduced by expression of CAAhR (constitutively active AhR), which
      activates transcription in a ligand-independent manner. Finally, we found that
      ARNT is critical for both hypoxic induction and the TCDD-mediated inhibition of
      CA9 expression.

PMID- 19154184
TI  - Titin isoform expression in aortic stenosis.
AB  - Titin is a giant sarcomeric protein that plays a major role in determining
      passive myocardial stiffness. The shorter N2B isoform results in a higher passive
      myocardial stiffness than the longer N2BA isoform. We hypothesised that the
      expression of the short N2B isoform would be increased in patients with aortic
      stenosis compared with healthy controls in response to pressure overload, in
      order to act as a modulator for the increased demand placed on the left ventricle
      during the early stages of the hypertrophic response. Myocardial biopsies were
      obtained from the left ventricle of 19 patients undergoing aortic valve
      replacement for aortic stenosis who had no significant co-existing coronary
      artery disease. Left ventricular biopsies were also obtained from 13 donor hearts
      for comparison. SDS-agarose gels revealed small N2B and large N2BA cardiac titin
      isoforms, with a mean N2BA/N2B ratio that was significantly decreased in the 19
      aortic stenotic patients compared with the 13 controls (0.66+/-0.04 in the normal
      donor hearts compared with 0.48+/-0.03 in patients with aortic stenosis; P=0.02).
      However, total titin remained unchanged (0.28+/-0.02 compared with 0.24+/-0.02
      respectively; P=0.29). In conclusion, the expression of less N2BA and more N2B
      titin in response to pressure overload may result in the generation of higher
      passive tension upon stretch to a given sarcomere length and this might affect
      cardiac performance.

PMID- 19154185
TI  - Identification of a cluster of residues in transmembrane segment 6 of domain III
      of the cockroach sodium channel essential for the action of pyrethroid
      insecticides.
AB  - A phenylalanine residue (Phe1519) in the sixth transmembrane segment of domain
      III (IIIS6) of the cockroach BgNa(v) sodium channel is required for the binding
      and action of pyrethroids. However, whether or not other residues in IIIS6
      participate in the action of pyrethroids remains to be determined. In the present
      study, we conducted a systematic analysis of 20 residues in IIIS6 of the BgNa(v)
      channel using alanine-scanning mutagenesis. Our results show that alanine
      substitutions of four residues, Ile1514, Gly1516, Phe1518 and Asn1522, altered
      sodium channel sensitivity to pyrethroid insecticides. Whereas the G1516A, F1518A
      and N1522A substitutions diminished sodium channel sensitivity to all seven
      pyrethroids examined, including four type I (lacking the alpha-cyano group at the
      phenoxybenzyl alcohol) and three type II (containing the alpha-cyano group)
      pyrethroids, the I1514A substitution enhanced sodium channel sensitivity to four
      type I and type II pyrethroids that contain the phenoxybenzyl alcohol only. We
      also show that alanine/lysine substitutions of Leu1521 and Ser1517 affected the
      action of BTX (batrachotoxin), but not pyrethroids. In the Kv1.2-based homology
      model of the open sodium channel, side chains of Ile1514, Phe1518 and Asn1522 are
      exposed towards helix IIS5 and linker IIS4-IIS5, which contain previously
      identified pyrethroid-interacting residues, whereas Ser1517 and Leu1521 face the
      inner pore where the BTX receptor is located. Thus the present study provides
      further evidence for structural models in which pyrethroids bind to the lipid
      exposed interface formed by helices IIIS6, IIS5 and linker helix IIS4-IIS5,
      whereas BTX binds to the pore-exposed side of the IIIS6 helix.

PMID- 19154187
TI  - The quality and influence of the journal.

PMID- 19154186
TI  - The Panton-Valentine leukocidin vaccine protects mice against lung and skin
      infections caused by Staphylococcus aureus USA300.
AB  - Methicillin-resistant Staphylococcus aureus is increasingly responsible for
      staphylococcal infections in the community. A large percentage of the community
      acquired methicillin-resistant (CA-MRSA) strains in the USA produce Panton
      Valentine leukocidin (PVL), which is associated with severe infections. The
      virulence of the clinical CA-MRSA strain USA300 was compared to that of its
      isogenic pvl-deleted mutant, and it was shown that PVL contributes to lung and
      muscle tissue destruction, respectively, in murine necrotizing pneumonia and skin
      infection models. Mice infected with the USA300 strain developed a dominant anti
      PVL response. The PVL subunits were therefore tested as vaccinogens against this
      isolate, and their vaccine efficacy correlated with both the route of vaccination
      and infection. These data suggest that PVL is a virulence factor in murine CA
      MRSA infections.

PMID- 19154188
TI  - Maternal prepregnancy body mass index and delivery of a preterm infant in
      missouri 1998-2000.
AB  - OBJECTIVE: To determine risk of delivering a preterm infant (<37 weeks) in
      overweight/obese women. DESIGN: Descriptive. SAMPLE: Population-based sample of
      169,881 singleton Missouri birth certificate records for 1998-2000. MEASURES:
      Prepregnancy body mass index (BMI): underweight BMI<19.8; normal BMI=19.8-24.9;
      overweight BMI=25-29.9; and obese BMI> or =30; and preterm birth (<37 completed
      weeks' gestation). RESULTS: In each BMI category, the percent of women who
      delivered a preterm infant is: underweight 11.5%, normal 8.3%, overweight 8.2%,
      and obese 8.5%. For women with a BMI of overweight (odds ratio [OR] 0.9, 95%
      confidence interval [CI]=0.8-0.9) and obese (OR 0.8, 95% CI=0.8-0.9), the risk of
      delivering a preterm infant decreased when compared with women with a BMI<19.8.
      Black (OR=2.5, 95% CI 2.4-2.6) and Hispanic (OR=1.4, 95% CI 1.2-1.5) women had a
      higher risk of preterm birth than White women when obesity, diabetes,
      hypertension, and prenatal care were controlled. Women with diabetes (OR=1.4, 95%
      CI=1.2-1.5), hypertension (OR=3.2, 95% CI=3.1-3.4), and those who smoked (OR=1.6,
      95% CI=1.6-1.7) were at increased risk for a preterm birth. CONCLUSIONS: Findings
      suggest that preconception and prenatal care focus on identification and
      management of risks associated with premature births and maternal risk factors
      such as diabetes, hypertension, and smoking.

PMID- 19154189
TI  - Comparing the influence of childhood and adult economic status on midlife obesity
      in Mexican American, white, and African American women.
AB  - OBJECTIVE: This research addresses the following 2 questions. What is the effect
      of childhood and adult economic status on midlife obesity in Mexican American
      women? How do these economic patterns in Mexican American women compare with
      patterns seen in White women and in African American women? METHOD: Data were
      drawn from the U.S. National Longitudinal Survey of Youths 1979-2002 waves. The
      sample consisted of 422 Mexican Americans, 2,090 Whites, and 1,195 African
      Americans. The economic indicator used for childhood economic status was parent
      education; for adult economic status, the participant's own education and adult
      per capita income were used. Unadjusted and adjusted odds ratios were estimated
      for the relationship between midlife obesity and economic indicator, stratified
      by race/ethnic group. RESULTS: There was an increased risk for midlife obesity
      with disadvantaged economic status measured during childhood and at midlife in
      Mexican American women. The economic effects on midlife obesity in Mexican
      American women were similar to those found for White, but not African American
      women. Few economic influences on obesity at midlife were found for African
      American women. CONCLUSIONS: Strategies that broadly improve the economic
      conditions of Mexican American women may be one important way to address the
      obesity epidemic in this population.

PMID- 19154190
TI  - Diabetes-related risk factors across Hispanic subgroups in the Hispanic health
      and nutritional examination survey (1982-1984).
AB  - OBJECTIVE: The Hispanic Health and Nutritional Examination Survey (HHANES) was
      utilized to examine diabetes-related risk factor variables between and among 3
      Hispanic subgroups. DESIGN: The study design that was conducted was descriptive
      using the HHANES secondary data set. SAMPLE: The sample included individuals
      between 20 and 74 years of age, self-identified as Mexican American, Puerto
      Rican, and/or Cuban American and had been told by a doctor that they had
      diabetes. MEASUREMENTS: The 5 diabetes-related risk factor variables were obesity
      measured by body mass index (BMI), hypertension by systolic blood pressure (SBP)
      and diastolic blood pressure (DBP), hyperlipidemia by cholesterol and
      triglyceride levels, renal insufficiency by blood urea nitrogen (BUN), and
      creatinine and fasting plasma glucose. RESULTS: This study demonstrates
      significant differences between specific subgroups through chi-square. SBP in
      Cuban Americans was significantly higher than that of Puerto Ricans (28.39 mmHg)
      and of Mexican Americans (25.94 mmHg). Cuban Americans also had significantly
      higher cholesterol values than Mexican Americans (88.49 mg/dL) and Puerto Ricans
      (84.49 mg/dL). The only significant difference for triglyceride was between
      Mexican Americans and Puerto Ricans (37.25 mg/dL). For BUN, there were
      significant differences when Cuban Americans (9.06 mg/dL) and Mexican Americans
      (2.20 mg/dL) were separately compared from Puerto Ricans, and Cuban Americans had
      significantly higher creatinine values than Puerto Ricans (0.38 mg/dL) and
      Mexican Americans (0.25 mg/dL). Through linear regression, significant
      differences for the association of each diabetes-related risk factor and the risk
      for diabetes complications were computed for each subgroup. For Mexican Americans
      and Puerto Ricans there were significant differences in overweight BMI (25.0-29.9
      kg/m2) and obesity (> or =30.0 kg/m2); for Mexican Americans, Puerto Ricans and
      Cuban Americans in elevated SBP (130-139 mmHg) or elevated DBP (80-89 mmHg), for
      high SBP (> or =140 mmHg) or high DBP (> or =90 mmHg), and for high glucose (> or
      =126 mg/dL); and for Mexican Americans in elevated triglyceride (> or =150
      mg/dL), elevated BUN (> or =21 mg/dL), and elevated creatinine (> or =1.5 mg/dL).
      CONCLUSION: The findings of this study will add to the diabetes and Hispanic
      literature highlighting the need to evaluate Hispanic subgroups in future health
      behavior and outcomes research.

PMID- 19154191
TI  - A program evaluation of postpartum/newborn home visitation services in aiken
      county, South Carolina.
AB  - OBJECTIVE: Home visiting programs for very young children seek to promote their
      health and development. We conducted a process and outcome evaluation of the
      Postpartum/Newborn Home Visit (PPNBHV) service in 1 county. DESIGN: A
      retrospective study of Aiken County Health records of live infant births in 2004
      was conducted. SAMPLE: A random sample of 176 infants who were born in 2004 and
      enrolled in the women, infants, and children's (WIC) program in the same year was
      selected. MEASURES: Process measures include timeliness of the home visit, and
      appropriateness of revisits. Outcome measures include age at WIC enrollment and
      immunization status at 6/9 months. RESULTS: Of the 176 infants, 76 (43%) received
      a home visit. Of these, 13 (17%) received the visit within the stipulated time
      frame. After controlling for potential confounders, infants who received a home
      visit were 4 times (95% CI 1.92-8.36) as likely to enroll early in the WIC
      program compared with those who did not. CONCLUSION: The PPNBHV service may
      contribute to early enrollment in the WIC program. Improvement in the timeliness
      of the visits is needed. Program monitoring and evaluation are necessary to
      ensure adherence, measure outcomes, and provide feedback for continuous quality
      improvement.

PMID- 19154192
TI  - Self-reported cultural competence of public health nurses in a Southeastern U.S.
      Public health department.
AB  - OBJECTIVE: Delivery of culturally competent public health nursing that can
      address health disparities is dependent on competent practice by nurses.
      Examining public health nurses' (PHNs') cultural competence provides a basis for
      planning and developing interventions to ensure competent care. Examine the
      cultural competence of PHNs. DESIGN: Descriptive, exploratory study examining the
      measured cultural competence of PHNs and their perceptions of delivery of
      culturally competent care. SAMPLE: A convenience sample of 31 PHNs participated.
      MEASUREMENTS: Participants completed the Cultural Competence Assessment tool and
      documented personal experiences and perceptions of culturally competent health
      care through open-ended questions. RESULTS: Most participants reported a moderate
      level of cultural competence. Cultural awareness and sensitivity scores were
      higher than scores for culturally competent behaviors. Participation in specific
      types of cultural competence training was significantly related to higher scores
      on cultural competence. Participants documented culturally competent care for a
      diverse clientele and requested additional diversity educational opportunities
      and interpreter services. CONCLUSIONS: The nurses had culturally competent
      knowledge and attitudes but were unable to fully and consistently enact these in
      practice. The need for appropriate cultural competence education and interpreter
      services addressing health disparities, as mandated in the Culturally and
      Linguistically Appropriate Services in Health Care standards, is emphasized.

PMID- 19154193
TI  - Using technology to expedite screening and intervention for domestic abuse and
      neglect.
AB  - OBJECTIVE: In response to escalation of community violence, the U.S. Department
      of Commerce funded Home Health VNA (HHVNA), serving the Merrimack River valley
      communities in Massachusetts and New Hampshire, for a project demonstrating
      innovative use of technology in screening for abuse and neglect. DESIGN: All
      health care providers in the HHVNA were trained in screening through tools loaded
      on their personal digital assistants. SAMPLE: The sample was comprised of
      patients served by HHVNA during the study period. INTERVENTION: When a patient
      screened positive, the health care provider mobilized resources, including social
      workers, the office of elder services, or the local department of social services
      office for same-day follow-up. OUTCOMES: Screening for abuse and neglect was
      mainstreamed into routine care. Health care providers noted significant reduction
      in redundant domestic abuse data collection. The close communication networks
      created enabled health care providers to mobilize resources, initiating same-day
      in-depth social work assessment and referrals to appropriate community agencies.
      Health care providers now transmit selected encrypted health information and
      mandated reports to official agencies. CONCLUSIONS: Wedding technology with
      health care professionals' skills and knowledge can move prevention of and early
      intervention for domestic abuse and neglect to a new level of efficacy.

PMID- 19154194
TI  - Rural public health policy models to address an evolving environmental asbestos
      disaster.
AB  - The health-related dangers of asbestos exposure were recognized early in the 20th
      century when occupational exposure was found to be associated with excess
      pneumoconiosis among asbestos industry workers. Today, the epicenter for
      examining the public health effects and the human toll that this toxin has had on
      a population is located in the rural community of Libby, MT. Rurality and
      multideterminants of health frame both the history of asbestos-related disease
      and the service/policy challenges within a community dealing with chronic illness
      and designation as a Superfund clean-up site. Despite efforts by public health
      advocates to address the lingering aftermath of an environmental disaster in this
      community, policy gaps exist that continue to impact the population's health. The
      purpose of this paper is to describe the history and outcomes of asbestos
      exposure in a rural community and discuss 3 models that provide public health
      policy insights related to rural health and health care for a community affected
      by both a sentinel and ongoing environmental event.

PMID- 19154195
TI  - Using nursing perspectives to inform public health nursing workforce development.
AB  - Recent national and regional public health workforce development efforts have
      been conducted through a framework of public health services research. Public
      health nurses (PHNs) are the single largest professional group in the formal
      public health system, and thus have the greatest potential for positively
      impacting our community health systems. Effective public health workforce
      development is contingent on examination of how PHNs themselves make meaning of
      their practice. This paper suggests that a nursing perspective should be used
      from which to conduct research surrounding PHN practice. Literature describing
      PHN practice and recent workforce assessment efforts are reviewed. Assumptions
      are identified regarding the nature of nursing knowledge, and a theoretical
      perspective for inquiry about PHN praxis is developed. Finally, a model is
      offered to illustrate the reciprocal influence of nursing science and public
      health nursing practice.

PMID- 19154196
TI  - Use of the public health nursing bag in the academic setting.
AB  - The nursing bag has been a vital tool for public and community health nurses
      since the early 1900s. However, the practice of utilizing the nursing bag has
      declined. This study sought to determine whether the practice of teaching
      students to use a public health nursing bag when making home visits should
      continue. Deans and directors of all schools of nursing with baccalaureate
      programs listed on the Commission on Collegiate Nursing Education Web site
      (n=437) were e-mailed an exploratory, descriptive self-report survey. Although
      32% of responding schools continued to utilize a standard public health bag
      during home visits, the majority did not. Lack of use of the bags was primarily
      related to cost and the lack of research demonstrating its efficiency in
      enhancing the home visit and its value in promoting infection control. The
      researchers concluded that they would continue to teach the use of the public
      health nursing bag. It provides a receptacle for equipment and supplies,
      reinforces the need to be prepared for a variety of situations, and serves as a
      reminder that handwashing is a routine part of every client's care, regardless of
      the setting.

PMID- 19154197
TI  - Addressing nonresponse bias in postal surveys.
AB  - Postal surveys are sometimes thought of as a simple option for collecting data in
      community-based studies; however, nurse researchers must exercise care in
      appropriately addressing the issue of nonresponse. In particular, both the
      reporters and the users of such research should look beyond survey response rates
      when considering nonresponse bias. This article describes the benefits of using
      postal surveys in public health nursing research, while noting the various
      potential sources of survey error. Particular attention is directed to the
      implications of low survey response rates, including decreased power, increased
      standard error, and nonresponse bias. The belief that increasing response rates
      will necessarily reduce nonresponse bias is discussed, with an emphasis on the
      need to identify the reasons for nonresponse and to be judicious in the use of
      strategies to reduce nonresponse bias. Common response-enhancement strategies are
      identified, while noting the potential for these strategies to increase
      nonresponse bias. Assessment of the presence and magnitude of nonresponse bias is
      discussed, and techniques for postsurvey data adjustment are noted. The need to
      consider nonresponse bias in designing all phases of the study is highlighted,
      and is exemplified with a case study.

PMID- 19154198
TI  - The public health nursing bag as tool and symbol.
AB  - This historical article presents information about the public health nurse's bag
      as used in mid-20(th) century America. The bag was an essential of practice,
      containing items necessary for providing home care to the sick, maternity
      nursing, health demonstrations, and other functions within the role of public
      health nursing agencies or private organizations in which nurses gave home care
      to multiple patients. Contents of the bag and specifications for their use are
      described. The historical use of the bag as both a repository for the instruments
      of skilled care and expert knowledge and of bag technique as a means of infection
      control may help explain the endurance of the black bag as a symbol of public
      health nursing.

PMID- 19154199
TI  - Extracellular cross-linking of maize arabinoxylans by oxidation of feruloyl
      esters to form oligoferuloyl esters and ether-like bonds.
AB  - Primary cell walls of grasses and cereals contain arabinoxylans with esterified
      ferulate side chains, which are proposed to cross-link the polysaccharides during
      maturation by undergoing oxidative coupling. However, the mechanisms and control
      of arabinoxylan cross-linking in vivo are unclear. Non-lignifying maize (Zea mays
      L.) cell cultures were incubated with l-[1-(3)H]arabinose or (E)-[U
      (14)C]cinnamate (radiolabelling the pentosyl and feruloyl groups of endogenous
      arabinoxylans, respectively), or with exogenous feruloyl-[(3)H]arabinoxylans. The
      cross-linking rate of soluble extracellular arabinoxylans, monitored on Sepharose
      CL-2B, peaked suddenly and transiently, typically at approximately 9 days after
      subculture. This peak was not associated with appreciable changes in peroxidase
      activity, and was probably governed by fluctuations in H(2)O(2) and/or
      inhibitors. De-esterified arabinoxylans failed to cross-link, supporting a role
      for the feruloyl ester groups. The cross-links were stable in vivo. Some of them
      also withstood mild alkaline conditions, indicating that they were not (only)
      based on ester bonds; however, most were cleaved by 6 m NaOH, which is a property
      of p-hydroxybenzyl-sugar ether bonds. Cross-linking of [(14)C]feruloyl
      arabinoxylans also occurred in vitro, in the presence of endogenous peroxidases
      plus exogenous H(2)O(2). During cross-linking, the feruloyl groups were oxidized,
      as shown by ultraviolet spectra and thin-layer chromatography. Esterified
      diferulates were minor oxidation products; major products were: (i) esterified
      oligoferulates, released by treatment with mild alkali; and (ii) phenolic
      components attached to polysaccharides via relatively alkali-stable (ether-like)
      bonds. Thus, feruloyl esters participate in polysaccharide cross-linking, but
      mainly by oligomerization rather than by dimerization. We propose that, after the
      oxidative coupling, strong p-hydroxybenzyl-polysaccharide ether bonds are formed
      via quinone-methide intermediates.

PMID- 19154200
TI  - Short panicle1 encodes a putative PTR family transporter and determines rice
      panicle size.
AB  - The architecture of the rice inflorescence, which is determined mainly by the
      number and length of primary and secondary inflorescence branches, is of
      importance in both agronomy and developmental biology. The position and number of
      primary branches are established during the phase transition from vegetative to
      reproductive growth, and several of the genes identified as participating in this
      process do so by regulating the meristemic activities of inflorescence. However,
      little is known about the molecular mechanism that controls inflorescence branch
      elongation. Here, we report on a novel rice mutant, short panicle1 (sp1), which
      is defective in rice panicle elongation, and thus leads to the short-panicle
      phenotype. Gene cloning and characterization indicate that SP1 encodes a putative
      transporter that belongs to the peptide transporter (PTR) family. This conclusion
      is based on the findings that SP1 contains a conserved PTR2 domain consisting of
      12 transmembrane domains, and that the SP1-GFP fusion protein is localized in the
      plasma membrane. The SP1 gene is highly expressed in the phloem of the branches
      of young panicles, which is consistent with the predicted function of SP1 and the
      sp1 phenotype. Phylogenetic analysis implies that SP1 might be a nitrate
      transporter. However, neither nitrate transporter activity nor any other
      compounds transported by known PTR proteins could be detected in either a Xenopus
      oocyte or yeast system, in our study, suggesting that SP1 may need other
      component(s) to be able to function as a transporter, or that it transports
      unknown substrates in the monocotyledonous rice plant.

PMID- 19154201
TI  - Wall-modifying genes regulated by the Arabidopsis homolog of trithorax, ATX1:
      repression of the XTH33 gene as a test case.
AB  - The plant cell wall is a dynamic structure playing important roles in the control
      of plant cell growth and differentiation. These processes involve global
      reprogramming of the genome driven by dynamic changes in chromatin structure. The
      chromatin modifier ARABIDOPSIS HOMOLOG OF TRITHORAX (ATX1) methylates lysine
      residue 4 on histone H3 (H3K4me), acting as an epigenetic mark on associated
      genes. The remarkable overrepresentation in the ATX1-regulated gene fraction of
      genes encoding plasma membrane and cell wall-remodeling activities suggested a
      link between two separate factors affecting growth, development and adaptation in
      Arabidopsis: the wall-modifying activities regulating cell extension, growth and
      fate, and the epigenetic mechanisms regulating chromatin structure and gene
      expression. A co-regulated fraction of specific wall-modifying proteins suggests
      that they may function together. Here, we study the ATX1-dependent expression of
      the gene encoding the wall-loosening factor XTH33 as a test case for development-
      and tissue-specific effects displayed by the chromatin modifier. In addition, we
      show that XTH33 is, most likely, an integral plasma membrane protein. A putative
      transmembrane domain is conserved in some, but not all, XTH family members,
      suggesting that they may be differently positioned when functioning as wall
      modifiers.

PMID- 19154202
TI  - Characterization of genes in the ASYMMETRIC LEAVES2/LATERAL ORGAN BOUNDARIES
      (AS2/LOB) family in Arabidopsis thaliana, and functional and molecular
      comparisons between AS2 and other family members.
AB  - The ASYMMETRIC LEAVES2 (AS2) gene is required for the generation of the flat and
      symmetrical shape of the leaf lamina in Arabidopsis. AS2 encodes a plant-specific
      protein with an AS2/LATERAL ORGAN BOUNDARIES (AS2/LOB) domain that includes a
      cysteine repeat, a conserved single glycine residue and a leucine-zipper-like
      sequence in its amino-terminal half. The Arabidopsis genome contains 42 genes,
      including AS2, that encode proteins with an AS2/LOB domain in their amino
      terminal halves, and these genes constitute the AS2/LOB gene family. In the
      present study, we cloned and characterized cDNAs that covered the putative coding
      regions of all members of this family, and investigated patterns of transcription
      systematically in Arabidopsis plants. Comparisons among amino acid sequences that
      had been deduced from the cloned cDNAs revealed eight groups of genes, with two
      or three members each, and high degrees of identity among entire amino acid
      sequences, suggesting that some members of the AS2/LOB family might have
      redundant function(s). Moreover, no member of the family exhibited significant
      similarity, in terms of the deduced amino acid sequence of the carboxy-terminal
      half, to AS2. Results of domain swapping between AS2 and other members of the
      family showed that the AS2/LOB domain of AS2 cannot be functionally replaced by
      those of other members of the family, and that only a few dissimilarities among
      respective amino acid residues of the AS2/LOB domain of AS2 and those of other
      members are important for the specific functions of AS2.

PMID- 19154203
TI  - A microRNA-transcription factor module regulates lateral organ size and
      patterning in Arabidopsis.
AB  - Precise regulatory mechanisms are necessary to properly control the enlargement
      and patterning of plant lateral organs. However, our understanding of the
      regulatory modules that govern both of these processes is limited. An emerging
      theme in plant development is microRNA (miRNA)-mediated gene regulation of
      transcription factors, including several NAC domain family members such as CUP
      SHAPED COTYLEDON2 (CUC2). We uncovered a novel allele of CUC2, cuc2-1D, that
      revealed important functions of miRNAs and CUC2 in a regulatory module governing
      lateral organ enlargement and patterning. cuc2-1D carried a single point mutation
      in the CUC2 miRNA target site, disrupting miRNA targeting. Disruption of the
      tight balance between CUC2 and its targeting miRNA, miRNA164, led to over
      accumulation of CUC2 mRNA and expansion of the CUC2 expression domain. cuc2-1D
      plants had enlarged vegetative and reproductive lateral organs relative to wild
      type plants. Mechanistically, these enlarged organs resulted from an increase in
      cell proliferation that occurred over a longer developmental time frame relative
      to wild-type. This organ enlargement was dependent on the receptor-like kinase,
      ERECTA (ER). This and lateral organ patterning phenotypes in cuc2-1D suggest that
      miRNA164 and CUC2 are critical regulators of both processes. Therefore, we
      propose that miRNA164 and CUC2 form a central regulatory module that acts as a
      governor of lateral organ patterning and expansion.

PMID- 19154204
TI  - Arabidopsis ING and Alfin1-like protein families localize to the nucleus and bind
      to H3K4me3/2 via plant homeodomain fingers.
AB  - In yeast and animals, tri- and dimethylation of histone H3 at lysine 4
      (H3K4me3/2) are markers of transcriptionally active genes that have recently been
      shown to be primary ligands for the plant homeodomain (PHD) finger. However, PHD
      fingers able to bind to H3K4me3/2 have not been identified in plants. Here, we
      identify 83 canonical PHD fingers in the Arabidopsis proteome database that are
      supported by both SMART and Pfam prediction. Among these, we focus on PHD fingers
      in ING (inhibitor of growth) homologues (AtING) and Alfin1-like (AL) proteins,
      which are highly similar to those in human ING2 and bromodomain PHD finger
      transcription factor (BPTF), based on predicted tertiary structures. ING proteins
      are found in yeast, animals and plants, whereas AL proteins exist only in plants.
      In vitro binding experiments indicated that PHD fingers in AtING and AL proteins
      in Arabidopsis can bind to H3K4me3, and, to a lesser extent, to H3K4me2. In
      addition, mutational analysis confirmed that a predicted aromatic cage and a
      specific conserved acidic residue are both crucial for binding to H3K4me3/2.
      Finally, we demonstrate that AtING and AL proteins are nuclear proteins that are
      expressed in various tissues of the Arabidopsis plant. Thus, we propose that ING
      and AL proteins are nuclear proteins that are involved in chromatin regulation by
      binding to H3K4me3/2, the active histone markers, in plants.

PMID- 19154205
TI  - The ABC transporter BcatrB from Botrytis cinerea exports camalexin and is a
      virulence factor on Arabidopsis thaliana.
AB  - Arabidopsis thaliana is known to produce the phytoalexin camalexin in response to
      abiotic and biotic stress. Here we studied the mechanisms of tolerance to
      camalexin in the fungus Botrytis cinerea, a necrotrophic pathogen of A. thaliana.
      Exposure of B. cinerea to camalexin induces expression of BcatrB, an ABC
      transporter that functions in the efflux of fungitoxic compounds. B. cinerea
      inoculated on wild-type A. thaliana plants yields smaller lesions than on
      camalexin-deficient A. thaliana mutants. A B. cinerea strain lacking functional
      BcatrB is more sensitive to camalexin in vitro and less virulent on wild-type
      plants, but is still fully virulent on camalexin-deficient mutants. Pre-treatment
      of A. thaliana with UV-C leads to increased camalexin accumulation and
      substantial resistance to B. cinerea. UV-C-induced resistance was not seen in the
      camalexin-deficient mutants cyp79B2/B3, cyp71A13, pad3 or pad2, and was strongly
      reduced in ups1. Here we demonstrate that an ABC transporter is a virulence
      factor that increases tolerance of the pathogen towards a phytoalexin, and the
      complete restoration of virulence on host plants lacking this phytoalexin.

PMID- 19154206
TI  - Identification of the novel protein QQS as a component of the starch metabolic
      network in Arabidopsis leaves.
AB  - Little is known about the role of proteins that lack primary sequence homology
      with any known motifs (proteins with unknown functions, PUFs); these comprise
      more than 10% of all proteins. This paper offers a generalized experimental
      strategy for identifying the functions of such proteins, particularly in relation
      to metabolism. Using this strategy, we have identified a novel regulatory
      function for Arabidopsis locus At3g30720 (which we term QQS for qua-quine
      starch). QQS expression, revealed through global mRNA profiling, is up-regulated
      in an Arabidopsis Atss3 mutant that lacks starch synthase III and has increased
      leaf starch content. Analysis of public microarray data using MetaOmGraph
      (metnetdb.org), in combination with transgenic Arabidopsis lines containing QQS
      promoter-GUS transgenes, indicated that QQS expression responds to a variety of
      developmental/genetic/environmental perturbations. In addition to the increase in
      the Atss3 mutant, QQS is up-regulated in the carbohydrate mutants mex1 and sis8.
      A 586 nt sequence for the QQS mRNA was identified by 5' and 3' RACE experiments.
      The QQS transcript is predicted to encode a protein of 59 amino acids, whose
      expression was confirmed by immunological Western blot analysis. The QQS gene is
      recognizable in sequenced Arabidopsis ecotypes, but is not identifiable in any
      other sequenced species, including the closely related Brassica napus. Transgenic
      RNA interference lines in which QQS expression is reduced show excess leaf starch
      content at the end of the illumination phase of a diurnal cycle. Taken together,
      the data identify QQS as a potential novel regulator of starch biosynthesis.

PMID- 19154207
TI  - Neurostructural imaging findings in children with post-traumatic stress disorder:
      brief review.
AB  - Child maltreatment has been associated with different psychiatric disorders.
      Studies on both animals and humans have suggested that some brain areas would be
      directly affected by severe psychological trauma. The pathophysiology of post
      traumatic stress disorder (PTSD) appears to be related to a complex interaction
      involving genetic and environmental factors. Advanced neuroimaging techniques
      have been used to investigate neurofunctional and neurostructural abnormalities
      in children, adolescents, and adults with PTSD. This review examined structural
      brain imaging studies that were performed in abused and traumatized children, and
      discusses the possible biological mechanisms involved in the pathophysiology of
      PTSD, the implications and future directions for magnetic resonance imaging (MRI)
      studies. Published reports in refereed journals were reviewed by searching
      Medline and examining references of the articles related to structural
      neuroimaging of PTSD. Structural MRI studies have been performed in adults and
      children to evaluate the volumetric brain alterations in the PTSD population. In
      contrast with studies involving adults, in which hippocampus volumetric reduction
      was the most consistent finding, studies involving children and adolescents with
      PTSD have demonstrated smaller medial and posterior portions of the corpus
      callosum.

PMID- 19154208
TI  - Normative data on Benton Visual Form Discrimination Test for older adults and
      impaired scores in Clinical Dementia Rating 0.5 participants: community-based
      study. The Osaki-Tajiri Project.
AB  - AIMS: The Benton Visual Form Discrimination test (VFD) is one of the non-verbal
      tests to assess the capacity for complex visual form discrimination. The purposes
      of the present study were to investigate the effects of age and education level
      of the VFD in healthy elderly subjects, rigorously excluding participants with
      Clinical Dementia Rating (CDR) 0.5, and the characteristics of VFD patterns in
      CDR 0.5 participants. METHODS: The 597 participants included CDR 0 (healthy
      elderly, n = 405), CDR 0.5 (mild cognitive impairment, n = 161), and CDR 1 and 2
      (dementia, n = 31). The VFD, Digit Forwards, Digit Backwards and Rey-Osterrieth
      Complex Figure Test (RCFT) copying were used for neuropsychological assessment.
      RESULTS: There were significant effects of age and education level on the VFD in
      healthy participants, and the CDR 0.5 group had a lower score on the VFD than the
      healthy group. Low performance on the VFD was associated with Digit Backward and
      RCFT copying in both healthy and CDR 0.5 participants. CONCLUSIONS: CDR 0.5
      participants exhibit deficits of visual form discrimination related to attention,
      visual construction and organization.

PMID- 19154209
TI  - Use of questionnaire infeasibility in order to detect cognitive disorders:
      example of the Center for Epidemiologic Studies Depression Scale in psychiatry
      settings.
AB  - AIM: To examine the extent to which cognitive disorders influenced the
      feasibility and accuracy of both the 20-item and the 10-item Center for
      Epidemiologic Studies Depression Scale (CES-D). METHODS: Cross-sectional analyses
      of 223 first-visit patients in a psychiatric clinic and 108 patients in a
      psychiatric department in a general hospital were conducted. To assess the
      influence of age, gender, and the presence of cognitive disorders on the
      feasibility of both versions of the CES-D, multiple logistic regression was
      performed with feasibility per se as the dummy dependent variable. In order to
      assess the accuracy of the CES-D, receiver operating characteristic (ROC)
      analysis was performed. RESULTS: The infeasibility of both types of CES-D were so
      strongly associated with the presence of cognitive disorders that it can be used
      as an indicator of cognitive impairment. Moreover, the 10-item CES-D had almost
      as acceptable an internal consistency reliability as the 20-item CES-D in the
      study settings. CONCLUSIONS: Information obtained from both versions of the CES-D
      could be utilized fully, using infeasibility as an indicator of cognitive
      disorders, in psychiatry settings. Other screening instruments with as heavy a
      cognitive load as the CES-D can also be used in the same manner as an indicator
      of cognitive disorders to save the need for instruments specifically designed for
      dementia. Such usage can decrease the burden on both the respondent and the
      clinician in clinical practice.

PMID- 19154210
TI  - How do general practitioners in Thailand diagnose and treat patients presenting
      with anxiety and depression?
AB  - AIMS: To examine general practitioners' (GPs') diagnosis of a case vignette
      presenting both anxiety and depression symptoms, and to understand their
      treatment preferences for the case. METHODS: A total of 1193 copies of a
      questionnaire were sent to doctors in primary care settings throughout Thailand.
      The questionnaire inquired about GPs' demographic information and training
      background, as well as common psychiatric diagnoses and drug prescriptions to
      patients in their practise. A case vignette of a patient presenting both anxiety
      and depression symptoms was then given, and GPs were asked to describe their
      diagnosis and treatment preferences. For comparison, postal questionnaires of the
      same case vignette were also sent to 40 psychiatrists practising in general
      hospitals, asking their opinion about the diagnosis and treatment preferences.
      RESULTS: A total of 434 questionnaires (36.4%) were returned. GPs reported that
      37.7% of their patients suffered from anxiety disorders while 28.4% suffered from
      depressive disorders. For the patient in the case vignette, GPs made a diagnosis
      of anxiety disorders (53.5%) more often than depressive disorders (31.9%),
      whereas the psychiatrists at the general hospitals made a diagnosis of depressive
      disorders (54%) more often than anxiety disorders (9.1%). One-third of the GPs
      prescribed only anxiolytics, while 15.4% prescribed only antidepressants. The
      most commonly prescribed antidepressant by GPs was amitriptyline, which 93% of
      GPs used at a dosage below 50 mg/day. Only 5.8% of them prescribed fluoxetine as
      antidepressant. The most frequently prescribed anxiolytic drug was diazepam
      (65.4%). The most common combination of drugs prescribed was amitriptyline and
      diazepam (38.7%). CONCLUSION: Compared to psychiatrists, GPs were more likely to
      diagnose anxiety than depression in patients with the same set of symptoms. They
      also preferred to use amitriptyline to treat depression, and prescribed the drug
      at a low dose. GPs in Thailand should be encouraged to prescribe fluoxetine for
      treatment of depression because it is safer and more convenient to use than
      tricyclic antidepressants.

PMID- 19154211
TI  - Alcohol consumption and transition of mild cognitive impairment to dementia.
AB  - AIM: Mild cognitive impairment (MCI) is a prodrome for dementia. Alcohol drinking
      patterns may affect cognitive functions and the effects may accumulate to a
      significant level at an advanced age. This study investigated the relationship
      between alcohol consumption and risks for dementia in a cohort of elderly
      patients with MCI. METHODS: Patients with suspected cognitive impairment were
      screened. One hundred and seventy-six patients who met the MCI criteria were
      enrolled. Lifetime and daily alcohol consumptions were assessed at baseline using
      a self-report questionnaire answered by patients and their caregivers. Patients
      were classified according to alcohol consumptions as abstainers, light-moderate
      and heavy drinkers. Global cognitive functions were assessed periodically with
      Mini-Mental State Examination (MMSE). Enrolled patients were followed for 2
      years. RESULTS: Of the 176 patients diagnosed as having MCI, 15 (8.5%) died, 13
      (7.4%) were lost to follow up, and 66 (37.5%) developed dementia during follow
      up. Light-moderate alcohol drinkers had better MMSE performance than abstainers
      (P < 0.05) and heavy drinkers (P < 0.01) 2 years after MCI diagnosis. Patients
      who consumed a total of <or=300 kg alcohol prior to MCI diagnosis had less
      cognitive decline than patients who consumed no (P < 0.05) or >300 kg alcohol (P
      < 0.01). Heavy drinkers had a higher risk for dementia than abstainers (P < 0.05)
      and light-moderate drinkers (P < 0.05) 2 years after MCI diagnosis. CONCLUSIONS:
      A J-shaped relationship may exist between alcohol consumption and cognitive
      decline in MCI patients. Light-moderate alcohol drinking may be associated with
      decreased risks for dementia in elderly patients with MCI.

PMID- 19154212
TI  - Anti-tumor necrosis factor-alpha therapy is associated with less frequent mood
      and anxiety disorders in patients with rheumatoid arthritis.
AB  - AIMS: The purpose of the present study was to examine the current prevalence of
      mood and anxiety disorders, and factors related to mood and anxiety disorders in
      patients with rheumatoid arthritis (RA). METHOD: The study sample included 83
      consecutive patients with RA who were admitted to a rheumatology outpatient
      clinic. Diagnoses of psychiatric disorders were determined using the Structured
      Clinical Interview for DSM-IV (SCID-I). To assess physical disability and disease
      activity, the Health Assessment Questionnaire and the Disease Activity Score,
      respectively, were used. RESULTS: The prevalence of any mood or any anxiety
      disorder was 43.4%. The two most common psychiatric diagnoses were major
      depression (21.7%) and generalized anxiety disorder (16.9%). Mood and anxiety
      disorders were unrelated to sociodemographic features, disease-related factors,
      and medications for RA except anti-tumor necrosis factor-alpha (TNF-alpha). These
      disorders, however, were identified less frequently in patients with RA receiving
      anti-TNF-alpha drugs compared to patients who did not receive such medications.
      CONCLUSION: Patients with RA frequently have mood and anxiety disorders, and anti
      TNF-alpha drugs may be useful for the mental status of these patients.

PMID- 19154213
TI  - Long-term efficacy and safety of aripiprazole in patients with schizophrenia,
      schizophreniform disorder, or schizoaffective disorder: 26-week prospective
      study.
AB  - AIMS: To date there have been no reports of long-term efficacy of aripiprazole in
      Asian populations. The aim of the present study was therefore to investigate the
      long-term efficacy, safety and tolerability of aripiprazole in a large number of
      patients with schizophrenia, schizophreniform disorder, or schizoaffective
      disorder in Korea. METHODS: This study was a prospective, multicenter, single
      group, 26-week open study of patients with schizophrenia, schizophreniform
      disorder, or schizoaffective disorder. A total of 300 Korean patients
      participated in the study. The primary efficacy measure was the Positive and
      Negative Syndrome Scale (PANSS) total score, and secondary efficacy measures
      included the PANSS positive and negative subscales, Clinical Global Impression
      Severity of Illness (CGI-S). Tolerability and safety were assessed by monitoring
      the frequency and severity of treatment-emergent adverse events, extrapyramidal
      symptoms (EPS), vital signs, weight, and laboratory tests. RESULTS: Aripiprazole
      produced rapid and significant improvements on all efficacy measures. As
      evidenced by PANSS total score, PANSS positive subscales and the CGI-S scores,
      first-episode drug-naive patients demonstrated significantly greater efficacy
      relative to patients who had previously experienced one or more episodes of
      relapse. Aripiprazole was associated with significant decrease of serum prolactin
      level. The subjects showed mild weight gain. CONCLUSION: Aripiprazole is an
      effective antipsychotic in the long-term treatment of both positive and negative
      symptoms. This study extends the findings of previous long-term studies, and has
      found that there is no significant difference with regard to ethnicity in
      response to aripiprazole.

PMID- 19154214
TI  - Lifetime substance abuse, family history of alcohol abuse/dependence and novelty
      seeking in eating disorders: comparison study of eating disorder subgroups.
AB  - AIM: To assess lifetime substance abuse, family history of alcohol
      abuse/dependence, and novelty seeking in three different eating disorder groups
      (anorexia nervosa-restrictive; anorexia nervosa-binge eating/purging; anorexia
      nervosa to bulimia nervosa). METHOD: A total sample of 371 eating disorder
      patients participated in the current study. Assessment measures included the
      prevalence of substance abuse and family history of alcohol abuse/dependence as
      well as the novelty-seeking subscale of the Temperament and Character Inventory
      Revised. RESULTS: Significant differences across groups were detected for
      lifetime substance abuse, with anorexia nervosa-restrictive individuals
      exhibiting a significant lower prevalence than the anorexia nervosa to bulimia
      nervosa and anorexia nervosa-binge eating/ purging patients (P < 0.01). For
      family history of alcohol abuse/dependence the same pattern was observed (P =
      0.04). Novelty seeking was associated with substance abuse (P = 0.002), with the
      anorexia nervosa to bulimia nervosa group exhibiting significantly higher scores
      on the novelty-seeking scale than the other two groups (P < 0.001). But family
      history of alcohol abuse/dependence was not related to novelty seeking (P =
      0.092). CONCLUSION: Lifetime substance abuse appears to be more prevalent in
      anorexia nervosa patients with bulimic features. Higher novelty-seeking scores
      may be associated with diagnosis cross-over.

PMID- 19154215
TI  - Prevalence and identification of alcohol use disorders among severe mental
      illness inpatients in Taiwan.
AB  - AIMS: A higher prevalence of alcohol use disorders (AUD) among psychiatric
      patients has been reported previously and the identification rate is relatively
      low. This study was designed to investigate the prevalence and identification of
      AUD among acute psychiatric inpatients with severe mental illness in a
      psychiatric hospital in Taiwan. METHODS: In a two-phase case identification
      strategy, the Alcohol Use Disorders Identification Test (AUDIT) was used as the
      first phase screening tool and the Structured Clinical Interview for DSM-IV-TR as
      the second phase diagnostic interview. The definition of identification was
      diagnosis of AUD on medical record at discharge. RESULTS: Of 400 respondents, 42
      screened positive and 358 screened negative. All screen-positive respondents and
      35 screen-negative respondents entered the second phase interview. The weighted
      lifetime prevalence of alcohol dependence was 8.3% (95% confidence interval [CI]:
      4.6-11.9%); alcohol abuse, 1.5% (95%CI: 0.2-2.8%); and AUD, 9.8% (95%CI: 5.7
      13.8%). The overall identification rate of AUD by medical staff was 28.2% (0% for
      alcohol abuse and 33.3% for alcohol dependence). Patients with mood disorders
      were prone to being undetected as having AUD. CONCLUSION: AUD comorbidity was
      common among inpatients with severe mental illness in Taiwan and was easily
      neglected by medical staff. It is necessary to use a validated screening
      questionnaire, such as AUDIT, to detect high-risk patients and then give
      appropriate interventions to enhance treatment outcome.

PMID- 19154216
TI  - Health impact of disaster-related stress on pregnant women living in the affected
      area of the Noto Peninsula earthquake in Japan.
AB  - AIMS: The present study assessed the health impact of stress on women who were
      pregnant during, or immediately after, a major earthquake and were living in the
      disaster area. Inherent resistance against the stress induced by the earthquake
      was also assessed. METHODS: The panel study consisted of 99 women who provided
      responses before and after delivery (response rate, 77.9%). Psychological impact
      was assessed on the Edinburgh Postnatal Depression Scale (EPDS), and stress
      resistance was assessed on the Sense of Coherence Scale (SOC). RESULTS: In
      adjusted multivariate models, the significant earthquake factor that predicted
      postnatal depression (EPDS) was 'existing anxiety about an earthquake' (beta =
      0.27, P = 0.01) and 'parity' (beta = -0.26, P = 0.02). The SOC during pregnancy
      significantly moderated between 'existing anxiety about an earthquake' and 'EPDS'
      (beta = -0.21, P = 0.02). During pregnancy the EDPS was a significant predictor
      of a physical abnormality during pregnancy or childbirth (odds ratio, 1.21; 95%
      confidence interval: 1.04-1.41). The SOC during pregnancy did not moderate
      between a physical abnormality and earthquake-related stress. CONCLUSIONS:
      Provision of an adequate support system and improvement of the SOC of young women
      affected by a disaster may be two ways of reducing the deleterious effects of
      disaster-related stress on maternal well-being.

PMID- 19154217
TI  - Follow-up study of suicide attempters who were given crisis intervention during
      hospital stay: pilot study.

PMID- 19154218
TI  - For publication: Tiagabine in the discontinuation of long-term benzodiazepine
      use.

PMID- 19154219
TI  - Association between neuronal cell adhesion molecule (NRCAM) single nucleotide
      polymorphisms and schizophrenia in a Korean population.

PMID- 19154220
TI  - Effects of dextromethorphan on electroconvulsive therapy.

PMID- 19154221
TI  - Case report: Effective treatment of Cotard's syndrome: quetiapine in combination
      with venlafaxine.

PMID- 19154222
TI  - Should adjunctive antipsychotic treatment be continued in remitted patients with
      depression?

PMID- 19154223
TI  - Increase of incidence of impaired fasting glucose in young schizophrenia
      patients.

PMID- 19154224
TI  - A case of adult onset metachromatic leukodystrophy.

PMID- 19154225
TI  - A soil bacterium regulates plant acquisition of iron via deficiency-inducible
      mechanisms.
AB  - Despite the abundance of iron in nature, it is the third most limiting nutrient
      for plants due to its minimal solubility in most soils. While certain soil
      microbes produce chelating agents that enhance the solubility of iron, the
      effectiveness of such siderophores in the assimilation of iron by plants is
      debated. With an increasing understanding that select soil microbes play a
      signaling role in activating growth and stress responses in plants, the question
      arises as to whether such symbionts regulate iron assimilation. Here we report a
      previously unidentified mechanism in which the growth-promoting bacterium
      Bacillus subtilis GB03 activates the plant's own iron acquisition machinery to
      increase assimilation of metal ions in Arabidopsis. Mechanistic studies reveal
      that GB03 transcriptionally up-regulates the Fe-deficiency-induced transcription
      factor 1 (FIT1), which is necessary for GB03-induction of ferric reductase FRO2
      and the iron transporter IRT1. In addition, GB03 causes acidification of the
      rhizosphere by enhancing root proton release and by direct bacterial
      acidification, thereby facilitating iron mobility. As a result, GB03-exposed
      plants have elevated endogenous iron levels as well as increased photosynthetic
      capacity compared with water-treated controls. In contrast, loss-of-function fit1
      2 mutants are compromised in terms of enhanced iron assimilation and
      photosynthetic efficiency triggered by GB03. In all studies reported herein, a
      physical partition separating roots from bacterial media precludes non-volatile
      microbial siderophores from contributing to GB03-stimulated iron acquisition.
      These results demonstrate the potential of microbes to control iron acquisition
      in plants and emphasize the sophisticated integration of microbial signaling in
      photosynthetic regulation.

PMID- 19154226
TI  - Natural variation in maize architecture is mediated by allelic differences at the
      PINOID co-ortholog barren inflorescence2.
AB  - We characterized allelic variation at barren inflorescence2 (bif2), a maize co
      ortholog of the Arabidopsis PINOID protein kinase (PID), and tested for trait
      associations with bif2 in both an association mapping population of 277 diverse
      maize inbreds and in the inter-mated B73 x Mo17 (IBM) linkage population. Results
      from the quantitative analyses were compared with previous reports of bif2
      phenotypes in mutagenesis studies. All three approaches (association, linkage,
      and mutagenesis) detect a significant effect of bif2 on tassel architecture.
      Association mapping implicates bif2 in an unexpectedly wide range of traits
      including plant height, node number, leaf length, and flowering time. Linkage
      mapping finds a significant interaction effect for node number between bif2 and
      other loci, in keeping with previous reports that bif2;spi1 and Bif2;Bif1 double
      mutants produce fewer phytomers. The Mo17 allele is associated with a reduced
      tassel branch zone and shows lower expression than the B73 allele in hybrid B73
      Mo17 F(1) inflorescences, consistent with the complete absence of tassel branches
      in the bif2 knockout mutant. Overall, these data suggest that allelic variation
      at bif2 affects maize architecture by modulating auxin transport during
      vegetative and inflorescence development.

PMID- 19154227
TI  - The vacuolar processing enzyme OsVPE1 is required for efficient glutelin
      processing in rice.
AB  - Rice (Oryza sativa L.) accumulates prolamines and glutelins as its major storage
      proteins. Glutelins are synthesized on rough endoplasmic reticulum as 57-kDa
      precursors; they are then sorted into protein storage vacuoles where they are
      processed into acidic and basic subunits. We report a novel rice glutelin mutant,
      W379, which accumulates higher levels of the 57-kDa glutelin precursor. Genetic
      analysis revealed that the W379 phenotype is controlled by a single recessive
      nuclear gene. Using a map-based cloning strategy, we identified this gene,
      OsVPE1, which is a homolog of the Arabidopsis betaVPE gene. OsVPE1 encodes a 497
      amino-acid polypeptide. Nucleotide sequence analysis revealed a missense mutation
      in W379 that changes Cys269 to Gly. Like the wild-type protein, the mutant
      protein is sorted into vacuoles; however, the enzymatic activity of the mutant
      OsVPE1 is almost completely eliminated. Further, we show that OsVPE1 is
      incorrectly cleaved, resulting in a mature protein that is smaller than the wild
      type mature protein. Taken together, these results demonstrate that OsVPE1 is a
      cysteine protease that plays a crucial role in the maturation of rice glutelins.
      Further, OsVPE1 Cys269 is a key residue for maintaining the Asn-specific cleavage
      activity of OsVPE1.

PMID- 19154228
TI  - Comparison of the A-Cc curve fitting methods in determining maximum ribulose 1.5
      bisphosphate carboxylase/oxygenase carboxylation rate, potential light saturated
      electron transport rate and leaf dark respiration.
AB  - A review of the literature revealed that a variety of methods are currently used
      for fitting net assimilation of CO2-chloroplastic CO2 concentration (A-Cc)
      curves, resulting in considerable differences in estimating the A-Cc parameters
      [including maximum ribulose 1.5-bisphosphate carboxylase/oxygenase (Rubisco)
      carboxylation rate (Vcmax), potential light saturated electron transport rate
      (Jmax), leaf dark respiration in the light (Rd), mesophyll conductance (gm) and
      triose-phosphate utilization (TPU)]. In this paper, we examined the impacts of
      fitting methods on the estimations of Vcmax, Jmax, TPU, Rd and gm using grid
      search and non-linear fitting techniques. Our results suggested that the fitting
      methods significantly affected the predictions of Rubisco-limited (Ac), ribulose
      1,5-bisphosphate-limited (Aj) and TPU-limited (Ap) curves and leaf photosynthesis
      velocities because of the inconsistent estimate of Vcmax, Jmax, TPU, Rd and gm,
      but they barely influenced the Jmax : Vcmax, Vcmax : Rd and Jmax : TPU ratio. In
      terms of fitting accuracy, simplicity of fitting procedures and sample size
      requirement, we recommend to combine grid search and non-linear techniques to
      directly and simultaneously fit Vcmax, Jmax, TPU, Rd and gm with the whole A-Cc
      curve in contrast to the conventional method, which fits Vcmax, Rd or gm first
      and then solves for Vcmax, Jmax and/or TPU with V(cmax), Rd and/or gm held as
      constants.

PMID- 19154229
TI  - Functional dissection of the cytosolic chaperone network in tomato mesophyll
      protoplasts.
AB  - The heat stress response is universal to all organisms. Upon elevated
      temperatures, heat stress transcription factors (Hsfs) are activated to up
      regulate the expression of molecular chaperones to protect cells against heat
      damages. In higher plants, the phenomenon is unusually complex both at the level
      of Hsfs and heat stress proteins (Hsps). Over-expression of both Hsfs and Hsps
      and the use of RNA interference for gene knock-down in a transient system in
      tomato protoplasts allowed us to dissect the in vivo chaperone functions of
      essential components of thermotolerance, such as the cytoplasmic sHsp, Hsp70 and
      Hsp100 chaperone families, and the regulation of their expression. The results
      point to specific functions of the different components in protection from
      protein denaturation and in refolding of denatured proteins.

PMID- 19154231
TI  - A sulphur deficiency-induced gene, sdi1, involved in the utilization of stored
      sulphate pools under sulphur-limiting conditions has potential as a diagnostic
      indicator of sulphur nutritional status.
AB  - A sulphate deficiency-induced gene, sdi1, has been identified by cDNA-amplified
      fragment length polymorphism (AFLP) analysis utilizing field-grown, nutrient
      deficient wheat (Triticum aestivum var. Hereward). The expression of sdi1 was
      specifically induced in leaf and root tissues in response to sulphate deficiency,
      but was not induced by nitrogen, phosphorus, potassium or magnesium deficiency.
      Expression was also shown to increase in plant tissues as the external sulphate
      concentration in hydroponically grown plants was reduced from 1.0 to 0.0 mm. On
      this basis, sdi1 gene expression has potential as a sensitive indicator of
      sulphur nutritional status in wheat. Genome-walking techniques were used to clone
      the 2.7-kb region upstream of sdi1 from genomic DNA, revealing several cis
      element motifs previously identified as being associated with sulphur responses
      in plants. The Arabidopsis thaliana gene most highly homologous to sdi1 is
      At5g48850, which was also demonstrated to be induced by sulphur deficiency, an
      observation confirmed by the analysis of microarray data available in the public
      domain. The expression of Atsdi1 was induced more rapidly than previously
      characterized sulphur-responsive genes in the period immediately following the
      transfer of plants to sulphur-deficient medium. Atsdi1 T-DNA 'knockout' mutants
      were shown to maintain higher tissue sulphate concentrations than wild-type
      plants under sulphur-limiting conditions, indicating a role in the utilization of
      stored sulphate under sulphur-deficient conditions. The structural features of
      the sdi1 gene and its application in the genetic determination of the sulphur
      nutritional status of wheat crops are discussed.

PMID- 19154233
TI  - Dendritic cells and melanoma therapy.

PMID- 19154234
TI  - Stepping on the GAS: a brake pedal for melanoma metastasis?

PMID- 19154235
TI  - Retention of the cyanobacterial neurotoxin beta-N-methylamino-l-alanine in
      melanin and neuromelanin-containing cells--a possible link between Parkinson
      dementia complex and pigmentary retinopathy.
AB  - beta-N-methylamino-l-alanine (BMAA), a neurotoxic amino acid produced by
      cyanobacteria, has been suggested to be involved in the etiology of a
      neurodegenerative disease complex which includes Parkinson-dementia complex
      (PDC). In PDC, neuromelanin-containing neurons in substantia nigra are
      degenerated. Many PDC patients also have an uncommon pigmentary retinopathy. The
      aim of this study was to investigate the distribution of (3)H-BMAA in mice and
      frogs, with emphasis on pigment-containing tissues. Using autoradiography, a
      distinct retention of (3)H-BMAA was observed in melanin-containing tissues such
      as the eye and neuromelanin-containing neurons in frog brain. Analysis of the
      binding of (3)H-BMAA to Sepia melanin in vitro demonstrated two apparent binding
      sites. In vitro-studies with synthetic melanin revealed a stronger interaction of
      (3)H-BMAA with melanin during synthesis than the binding to preformed melanin.
      Long-term exposure to BMAA may lead to bioaccumulation in melanin- and
      neuromelanin-containing cells causing high intracellular levels, and potentially
      changed melanin characteristics via incorporation of BMAA into the melanin
      polymer. Interaction of BMAA with melanin may be a possible link between PDC and
      pigmentary retinopathy.

PMID- 19154236
TI  - Wild type and melanoma-associated mutant p16(IN4a) proteins do not oligomerize in
      vivo.

PMID- 19154237
TI  - Global prescribing: a transition.

PMID- 19154238
TI  - Revisiting "suicide proofing" an inpatient unit through environmental safeguards:
      a review.
AB  - PURPOSE: This article identifies the types of environmental safeguards within
      psychiatric facilities that can be implemented to protect suicidal individuals
      from harming themselves. The history and variety of safeguards are discussed, as
      well as recommendations for administrators regarding making their units safer.
      CONCLUSION: The use of environmental safeguards is one of the first steps in
      decreasing inpatient suicides. PRACTICE IMPLICATIONS: Inpatient nurses need to be
      aware of the environmental dangers in their units and of the safeguards that
      should be implemented. Recommendations include training programs, environmental
      tours, and effecting indicated structural changes.

PMID- 19154239
TI  - Informal role expansion in Australian mental health nursing.
AB  - PURPOSE: This study aims to determine the extent to which community mental health
      nurses are currently practicing beyond the traditional scope of nursing practice.
      DESIGN AND METHODS: A self-administered questionnaire was distributed to
      community mental health nurses in Victoria, Australia. FINDINGS: The majority of
      participants reported routine involvement in practices that would normally be
      considered beyond the scope of nursing practice, such as prescribing, ordering
      diagnostic tests, and referral to specialists. PRACTICE IMPLICATIONS: The extent
      to which the current mental health service system is dependent upon nurses
      transgressing professional and legal boundaries warrants further study.
      Psychiatrists and community mental health nurses need to work collaboratively to
      understand their respective knowledge and skills and to be clear about how they
      take responsibility for client care.

PMID- 19154240
TI  - The risks and benefits of switching antipsychotics: a case study approach.
AB  - PURPOSE: Progression of metabolic illness in a patient with schizophrenia who was
      stabilized on an atypical antipsychotic is described using a case study
      framework. Risks and benefits of staying on current treatment versus switching to
      another agent and switching strategies are described. CONCLUSIONS: Switching an
      antipsychotic with more favorable side effects may improve metabolic parameters
      if other weight loss strategies have failed. Switching or stopping medications
      too quickly may exacerbate psychiatric symptoms. There is little evidence to
      support which is the best switching strategy. PRACTICE IMPLICATIONS: The
      psychiatric mental health nurse practitioner carries a significant responsibility
      of discussing risks and benefits of switching and closely monitoring the patient
      during a switch of medications. Ensuring that the patient decides and agrees upon
      the treatment plan will improve the overall outcome.

PMID- 19154241
TI  - Long-term lithium therapy leading to hyperparathyroidism: a case report.
AB  - PURPOSE: This paper reviews the effect of chronic lithium therapy on serum
      calcium level and parathyroid glands, its pathogenesis, and treatment options. We
      examined the case of a lithium-treated patient who had recurrent hypercalcemia to
      better understand the disease process. CONCLUSION: Primary hyperparathyroidism is
      a rare but potentially life-threatening side effect of long-term lithium therapy.
      Careful patient selection and long-term follow-up can reduce morbidity. PRACTICAL
      IMPLICATIONS: As much as 15% of lithium-treated patients become hypercalcemic. By
      routinely monitoring serum calcium levels, healthcare providers can improve the
      quality of life of this patient group.

PMID- 19154242
TI  - Electroconvulsive therapy.

PMID- 19154243
TI  - The psychiatric nurse in the burn unit.

PMID- 19154244
TI  - Different generations review One Flew Over the Cuckoo's Nest Milos Forman
      (director).

PMID- 19154245
TI  - Clap if you believe in Batman The Dark Knight Christopher Nolan (director).

PMID- 19154247
TI  - Prescriptive authority for nurses: the Canadian perspective.
AB  - PURPOSE: This study aims to describe the role of prescriptive authority for
      nurses within Canada. CONCLUSIONS: Prescriptive authority for Canadian nurses is
      linked to the development of advanced practice nursing generally and nurse
      practitioners specifically. Recent legislative changes allow nurse practitioners
      to function more independently regardless of the availability of medical
      practitioners. The smaller population results in less legislative variety for
      specific nurse practitioner specialty areas. Facilitators and barriers to
      implementing effective prescriptive authority remain as challenges and mirror
      findings from other literature. PRACTICE IMPLICATIONS: Role clarity, strength in
      nursing focus, and support from administrators and legislation are required for
      prescriptive authority to be fully enacted.

PMID- 19154248
TI  - Nurse practitioners and medical practice: opposing forces or complementary
      contributions?
AB  - PURPOSE: The medical profession in Australia has expressed concern about the
      expansion of nursing practice into areas that are traditionally the domain of
      medicine. Particular apprehension is raised in relation to the prescription of
      medications. This paper will consider and critique the argument that the standard
      of care provided by a nurse practitioner would be of lesser quality than that
      provided by a medical practitioner. CONCLUSIONS: Despite the medical profession's
      opposition for nurse practitioner roles, there is little evidence suggesting that
      the quality of services offered by a nurse practitioner would be inferior.
      PRACTICE IMPLICATIONS: Available evidence suggests that care and treatment from
      nurse practitioners in primary health care is equal to that provided by medical
      practitioners.

PMID- 19154249
TI  - Mental health nurse prescribing in New Zealand and the United kingdom: comparing
      the pathways.
AB  - PURPOSE: Prescriptive authority in the area of mental health care is
      significantly different between New Zealand and the United Kingdom. Exploring the
      educational preparation and context differences aids understanding of the present
      dearth of mental health nurse prescribers in New Zealand. CONCLUSIONS: The
      barriers experienced in implementation and extension of prescribing rights have
      been similar in both countries. PRACTICE IMPLICATIONS: Until roles change,
      registered nurses in New Zealand may be reluctant to undertake the challenging
      and demanding step to gain prescribing rights. The potential for nurses to make a
      difference in the lives of people with mental illness in New Zealand is therefore
      constrained.

PMID- 19154250
TI  - Prescribing by mental health nurses: the UK perspective.
AB  - PURPOSE: This article aims to discuss the growth of mental health nurse (MHN)
      prescribing in the United Kingdom as an exemplar for readers to compare progress
      in their own countries and context. This study also aims to provide a historical
      overview of this process in the United Kingdom where MHNs prescribe safely and
      competently. CONCLUSIONS: Finally, evidence has shown that MHNs with prescriptive
      authority are competent when prescribing when compared to psychiatrists. PRACTICE
      IMPLICATIONS: Despite organizational barriers and educational concerns, MHN
      prescribing is becoming embedded in the healthcare context in the United Kingdom.

PMID- 19154251
TI  - The changing face of paediatric allergy.

PMID- 19154252
TI  - Pediatric Allergy and Immunology is gaining in strength and profile.

PMID- 19154253
TI  - Mechanisms of food allergy.
AB  - Allergy type sensitization occurring in the gut results from a break in oral
      tolerance, mostly occurring in early childhood. In these patients, a minute
      amount of the large load of potential food allergens not only will result in
      immunoglobulin E (IgE) type sensitization mostly, but also in food allergies
      resulting from other mechanisms including eosinophil-driven disease or resulting
      from T-cell-mediated inflammation. Symptoms elicited by subsequent exposure to
      foods in these patients will be mostly in relation to the mechanism of the
      disease. In this educational review series, we described three cases of food
      allergy, first, a child with typical IgE-mediated food allergy, second, a child
      with eosinophilic proctocolitis and in the third patient, we will address
      tolerance acquisition mechanisms. These cases are discussed with regards to their
      specific immune events.

PMID- 19154254
TI  - Transforming growth factor-beta is elevated in unpasteurized cow's milk.
AB  - Unpasteurized milk consumption was associated with less atopy prevalence. Not
      only microbial load but also fatty acids and cytokines such as transforming
      growth factor-beta(1) (TGF-beta(1)) may play a role on the effect of
      unpasteurized milk. Levels of TGF-beta(1) in different cow's milk samples were
      evaluated: we consider raw unpasteurized milk before and after boiling,
      commercial pasteurized and micro-filtrated cow's milk and different commercially
      available cow's milk formulas. TGF-beta(1) concentration in raw unpasteurized
      cow's milk was 642.0 +/- 52.9 pg/ml before boiling and decreased significantly
      after boiling (302.7 +/- 50.59 pg/ml) (p < 0.05). TGF-beta(1) concentrations were
      also significantly lower in commercial pasteurized milk (246.2 +/- 43.15 pg/ml)
      and in commercial micro-filtrated milk (213.0 +/- 31.6 pg/ml) in comparison to
      unpasteurized unboiled milk (p = 0.002). The levels of TGF-beta(1) in all formula
      samples were below the threshold of detectability for the assays. As TGF-beta(1)
      in the milk may contribute to the development of the immature gastrointestinal
      tract by influencing IgA production and oral tolerance induction, we suggest to
      consider not only the microbial compounds but also the cytokine patterns to
      explain the protective effect of unpasteurized cow's milk on allergic disorders.

PMID- 19154255
TI  - Increasing prevalence of asthma, allergic rhinitis but not eczema in 5- to 8-yr
      old Maltese children (ISAAC).
AB  - The International Study of Asthma and Allergies in Childhood (ISAAC) was the
      first worldwide study carried out with standardized questionnaires in order to
      create a reliable global map of childhood allergy. Phase 1 of the study was
      carried out in the Maltese Islands in 1994/95 while a similar study (phase 3) was
      repeated 7 yr later (2001/02). In this paper, the data obtained from 3816 5- to 8
      yr-olds (80% response rate) in phase 3 were compared to that obtained from 3509 5
      to 8-yr-olds (78.5% response rate) in phase 1 of the study in order to evaluate
      whether the problem of allergic conditions in Maltese schoolchildren was indeed
      changing. About 30.2% (phase 3) vs. 19.1% (phase 1) (p < 0.0001) of the
      participants were wheezers 'ever' while 14.8% vs. 8.8% (p < 0.0001) were current
      wheezers and 14.8% vs. 7.5% (p < 0.0001) were labelled as asthmatics. Of these
      wheezing children, 13.3% vs. 6.2% (p = 0.0002) had a wheezing episode severe
      enough to limit speech. Nasal problems were present in 28.8% of Maltese children
      in 2001 and in 23.4% in 1994 (p < 0.0001) and 24.4% vs. 20.7% (p < 0.0001) of all
      respondents persisted with these symptoms up to the year of answering the
      questionnaire. Hayfever had been diagnosed in 22.2% vs. 14.7% (p < 0.0001) of all
      the children. About 6.7% vs. 7.0% (p = 0.61) of respondents had an recurring
      itchy rash suggestive of eczema for at least 6 months of their lives and 5.4.%
      vs. 5.5% had it currently. In 1994, the prevalence of wheezing and eczema were
      slightly lower than the global mean, unlike the case of rhinitis, which in Malta
      was commoner than the world average, while in 2001 wheezing together with
      rhinitis surpassed the global mean as well. These results indicate a rising
      prevalence of wheezing and rhinitis but not eczema in Maltese children. Asthma
      seemed to be better controlled and all three allergic conditions more likely to
      be diagnosed.

PMID- 19154256
TI  - On mechanism of action of sublingual immunotherapy.

PMID- 19154258
TI  - Protein expression of nuclear receptors in human and murine tissues.
AB  - Nuclear receptors (NR) are transcriptional regulators expressed in a variety of
      tissues and they play important roles in embryonic development, organogenesis and
      metabolic homeostasis. In order to investigate the tissue-specific expression
      pattern of NR, mouse anti-human monoclonal antibodies newly generated against
      various NR. Specificities of the antibodies were confirmed on immunoblotting
      using overexpressed proteins. Most of the antibodies recognized intrinsic
      protein. Among 60 monoclonal antibodies generated, 32 were applicable for
      immunohistochemistry. The expression pattern of NR in human liver and pancreas
      was confirmed on immunohistochemical staining using these antibodies. The P2
      promoter-driven hepatocyte nuclear factor 4alpha (HNF4alpha) isoform and
      progesterone receptor were expressed in pancreatic alpha-cells, but not beta
      cells in the human pancreas, suggesting an unknown role of these NR in diabetes
      mellitus. These antibodies were also useful for immunohistochemistry of the
      murine liver and pancreas. Immunoblotting using these antibodies produced similar
      corresponding bands both in human and mouse tissues. These monoclonal antibodies
      may serve as powerful tools to detect tissue-specific localization of NR and
      provide a platform for future studies of NR in human and murine tissues.

PMID- 19154259
TI  - Sodium/iodide symporter expression in primary lung cancer and comparison with
      glucose transporter 1 expression.
AB  - The aim of the present study was to evaluate the expression of sodium/iodide
      symporter (NIS) and glucose transporter 1 (Glut1) in 139 primary lung cancers on
      immunohistochemistry, and to determine the diagnostic utility of NIS as an
      imaging reporter. Immunoreactivity for NIS and Glut1 was noted in 75 (54.0%) and
      72 (51.8%) of the 139 cases, respectively. Analysis of NIS expression on Western
      blot confirmed the immunohistochemistry. NIS expression was significantly higher
      in the adenocarcinomas than in the other carcinomas, and Glut1 expression was
      significantly higher in the squamous cell carcinomas than in the other carcinomas
      (each P < 0.0001). The frequency of NIS expression in those carcinomas lacking
      Glut1 expression was significantly higher than in those with Glut1 expression (P
      = 0.012). Among 64 adenocarcinomas, the frequency of the NIS(+)/Glut1(-)
      phenotype was 61.0%, which was the most frequent expression pattern. By studying
      the expression pattern of NIS in lung cancer, the present paper provides a
      helpful foundation for examining the potential utility of NIS-mediated
      radioiodide as an alternative diagnostic modality, especially for the management
      of patients with lung adenocarcinoma lacking Glut1 expression.

PMID- 19154260
TI  - Clinicopathological and immunohistochemical features of three pilomyxoid
      astrocytomas: comparative study with 11 pilocytic astrocytomas.
AB  - Pilomyxoid astrocytoma, first described by Tihan et al., was recently included as
      an established variant of pilocytic astrocytoma in the World Health Organization
      classification of CNS tumors. Histologically, it much resembles pilocytic
      astrocytoma, but monomorphic myxoid tumor of pilocytic cells with prominent
      angiocentric growth pattern without Rosenthal fibers or eosinophilic granular
      bodies is characteristic of pilomyxoid astrocytoma. Pilomyxoid astrocytoma is
      thought to be more aggressive with more frequent local recurrence as well as
      cerebrospinal spread. The authors recently encountered a case of pilomyxoid
      astrocytoma, therefore the purpose of the present study was undertake a
      retrospective review of pilocytic astrocytomas previously diagnosed during the
      past 10 years. Consequently, two of them were found to have histological features
      suggestive of pilomyxoid astrocytoma and both involved multiple recurrence,
      suggesting aggressive behavior in comparison to pilocytic astrocytoma. Therefore,
      knowledge of this entity is essential to surgical pathologists and clinicians for
      patient management.

PMID- 19154261
TI  - Actin expression in neural crest cell-derived tumors including schwannomas,
      malignant peripheral nerve sheath tumors, neurofibromas and melanocytic tumors.
AB  - Tumors that originate from neural crest-derived cells represent a heterogeneous
      group of neoplasms including benign and malignant tumors with melanocytic and
      schwannian differentiation. The immunophenotype of these tumors is well known but
      little is known about the expression of smooth muscle/myofibroblastic markers in
      these tumors. A total of 590 neural crest-derived tumors (50 benign schwannomas,
      five malignant peripheral nerve sheath tumors, 80 neurofibromas, 240 nevocytic
      nevi, 115 primary melanomas, and 100 melanoma metastases) were studied with
      respect to alpha-smooth muscle actin and muscle-specific actin expression. alpha
      Smooth muscle actin and muscle-specific actin-positive tumor cells with a co
      expression of S-100 protein were found in one benign schwannoma, one primary
      cutaneous melanoma, and four melanoma metastases. Four of these cases were
      examined ultrastructurally, but typical actin filaments with focal densities were
      not found in any of the four. Other immunohistochemical markers examined
      including desmin, h-caldesmon and smooth muscle myosin heavy chain were negative
      in the tumor cells. The present results suggest that neural crest-derived tumors
      could show expression of alpha-smooth muscle actin on rare occasion.

PMID- 19154262
TI  - Pleomorphic carcinoma with osteoclastic giant cells of the breast:
      immunohistochemical differentiation between coexisting neoplastic and reactive
      giant cells.
AB  - Herein is described a unique case of breast carcinoma with two different types of
      giant cells noted in both cytological and histological specimens. A 51-year-old
      Japanese woman noticed a hard mass in the upper outer quadrant of her left
      breast. Aspiration cytology exhibited numerous anaplastic giant cells; the
      cytological diagnosis was high-grade ductal carcinoma, although a few
      osteoclastic giant cells were also observed. A left simple mastectomy and
      sentinel lymph node biopsy were performed. Histologically, approximately 90% of
      the tumor was composed of giant cells; conventional invasive ductal carcinoma and
      ductal carcinoma in situ were found focally at the periphery of the tumor. The
      main part of the tumor contained both anaplastic, neoplastic giant cells and non
      neoplastic, osteoclastic giant cells that were distinguishable from nuclear
      atypism. The presence of the two types of giant cells was also confirmed on
      immunohistochemistry using a histiocytic marker (CD68) and two epithelial markers
      (AE1/AE3 and CAM5.2). Based on the latest World Health Organization
      classification, the diagnosis was pleomorphic carcinoma with osteoclastic giant
      cells. To the authors' knowledge there has been no previous report on this
      subject except for a single case mentioned in Rosen's Breast Pathology.

PMID- 19154263
TI  - Gastrointestinal stromal tumor in the duodenum exhibiting hemangiopericytoma-like
      histological pattern.
AB  - Reported herein is a gastrointestinal stromal tumor (GIST) that exhibited a
      hemangiopericytoma (HPC)-like histological pattern. Such a morphological variant
      of GIST has not been described previously. A 57-year-old woman presented with
      bloody stools. On upper digestive tract endoscopy a submucosal tumor of diameter
      2 cm was detected at the duodenal bulb, and enucleated. Grossly, the tumor was
      well-circumscribed, grayish to whitish, and solid, and its central portion was
      ulcerated. Histology indicated round to fusiform tumor cells that had
      proliferated around branching vessels that had a staghorn configuration.
      Immunohistochemistry showed that the tumor cells were diffusely positive for
      vimentin and KIT; partially positive for CD34 and muscle actin; and negative for
      alpha-smooth muscle actin. On mutation analysis a 42 bp deletion was found from
      codons 560 to 573 of exon 11 of the KIT gene, which is a mutational hot spot of
      GIST. In diagnosis of gastrointestinal tract tumors with an HPC-like histological
      pattern, pathologists should consider the possibility of GIST.

PMID- 19154264
TI  - Pancreatic serous microcystic adenoma with extensive oncocytic change.
AB  - Herein is reported a case of pancreatic serous microcystic adenoma with extensive
      oncocytic change in a 73-year-old woman. Histologically the tumor consisted of
      numerous small cysts, separated by thin or broad fibrous septa. These cysts were
      lined with uniform cells having abundant eosinophilic granular cytoplasm, which
      was negatively or weakly stained with PAS. Immunohistochemically, the cyst-lining
      cells were positive for cytokeratin (CK) 7, CK19, MUC1, MUC6, alpha-inhibin, and
      neuron-specific enolase (NSE), and negative for CK8, CK20, MUC2, and MUC5AC;
      these immunoprofiles coincide with those of serous microcystic adenoma.
      Immunostaining with anti-mitochondrial antibody showed dense granular positivity
      in the cytoplasm, which suggested an oncocytic phenotype. Thus, this case is
      considered a variant of serous microcystic adenoma characterized by extensive
      oncocytic change. To the authors' knowledge no similar case has been reported in
      the literature. It may pose problems in the differential diagnosis of the cystic
      pancreatic tumors with oncocytic change, but can be diagnosed on histology and
      immunohistochemistry.

PMID- 19154265
TI  - Parathyroid carcinoma with anaplastic feature: association of a p53 gene mutation
      with anaplastic transformation.
AB  - Parathyroid carcinoma is a rare neoplasm that accounts for only 1-3% of cases of
      primary hyperparathyroidism. Parathyroid carcinoma is a well-differentiated tumor
      that is sometimes difficult to differentiate histopathologically from its benign
      counterpart, parathyroid adenoma. The molecular mechanism of parathyroid
      carcinogenesis remains unknown, and investigators have reported that
      abnormalities of the p53 gene do not play a significant role in parathyroid
      carcinogenesis, unlike in other human malignancies. The present report describes
      parathyroid carcinoma with anaplastic transformation of differentiated
      parathyroid carcinoma in a patient with primary hyperparathyroidism. Nuclear
      accumulation of p53 protein was found in anaplastic carcinoma cells but not in
      differentiated carcinoma cells. Polymerase chain reaction-single-strand
      conformation polymorphism followed by direct sequencing showed that anaplastic
      carcinoma cells carried a missense mutation at codon 248 (CGG to CAG) of the p53
      gene, while the remaining differentiated carcinoma cells had the wild-type p53
      gene. These findings suggest that the p53 gene mutation is associated with
      anaplastic transformation of parathyroid carcinoma.

PMID- 19154266
TI  - Primary osteosarcoma of the breast.
AB  - Presented herein is a case of primary pure osteosarcoma of the breast. A 59-year
      old woman noticed a left breast tumor. Mammography showed a cluster of crushed
      stone-like calcifications, which gave the tumor a raw cotton-like appearance.
      Malignancy was suspected on fine-needle aspiration cytology of the tumor. An
      excisional biopsy was performed. The tumor was 2.0 x 2.4 cm in size.
      Histopathologically the tumor was composed of diffuse atypical cells with mitosis
      and a lot of bone. Atypical cells were thought to be neoplastic osteoblasts.
      Multinucleated osteoclastic cells were interspersed with osteoblasts. Spindle
      cells were found at the verge of the tumor. A few entrapped tubular structures
      were seen. Immunohistochemistry indicated that neoplastic osteoblastic cells of
      the tumor were stained positively for vimentin, but negatively for epithelial
      markers; which suggested that the tumor cell elements originated from epithelial
      cells. This tumor was diagnosed as primary extraskeletal osteosarcoma. Partial
      resection was additionally performed around the excisional biopsy without
      dissection of the axillary lymph nodes. Bone radionuclide scan after operation
      showed no abnormal uptake. At 5 years after surgery no recurrence was seen.

PMID- 19154267
TI  - Histogenesis of metaplastic breast carcinoma and axillary nodal metastases.
AB  - A 40-year-old breast-feeding woman presented with left breast swelling. On
      physical examination a 7 cm mass was found in the breast. Because biopsy
      demonstrated malignant tissue, mastectomy with axillary nodal dissection was
      performed. Pathological findings were consistent with metaplastic breast
      carcinoma with nodal metastases. The primary tumor consisted of three types of
      invasion: ductal, squamous, and sarcomatous. Furthermore, three morphological
      transitions were observed: ductal-squamous, ductal-sarcomatous, and squamous
      sarcomatous. Ductal-squamous (12/18 microscopy slides) and squamous-sarcomatous
      transitions (10/18) were more commonly observed than ductal-sarcomatous
      transition (3/18). Furthermore, immunohistochemistry showed loss of epithelial
      marker (cytokeratin) and acquisition of mesenchymal markers (vimentin and alpha
      smooth muscle actin) in the sarcomatous component. These findings suggested that
      epithelial-mesenchymal transition had occurred in the tumor and that two
      pathways, ductal-squamous-sarcomatous and ductal-sarcomatous transition, were
      involved in progression of metaplastic breast carcinoma. The main pathway
      appeared to be ductal-squamous-sarcomatous transition. Regarding the nodal
      metastases, of 13 positive nodes, ductal, squamous, and sarcomatous components
      were observed in 13, seven, and two nodes, respectively. Moreover, as in the
      primary tumor, ductal-squamous and squamous-sarcomatous transitions were
      observed. This suggested that the ductal component metastasized to the nodes and
      that epithelial-mesenchymal transition subsequently occurred within the nodes.

PMID- 19154268
TI  - The effect of maximum bite force on alveolar bone morphology.
AB  - OBJECTIVES: To investigate to what extent maximum bite force contributes to
      alveolar bone morphology parameters, i.e. alveolar thickness, shape and arch
      width. DESIGN: An observational cross-sectional survey. SETTING AND SAMPLE
      POPULATION: One hundred and fifty one 12- to 14-year-old students from a
      secondary school in Hatyai City, Songkhla Province, Thailand. MATERIAL AND
      METHODS: Height, weight and maximum bite force of each subject were recorded.
      Alveolar bone morphology parameters were measured from study models. RESULTS:
      Maximum bite force moderately correlated with alveolar thickness and shape (r =
      0.31-0.44, p < 0.001), but weakly correlated with arch width (r = 0.03-0.05, p >
      0.05). After adjusting for gender and body mass index (BMI), the maximum bite
      force significantly determined alveolar thickness and shape (p < 0.001),
      accounting for 10-20% of the variations. Boys were associated with larger
      posterior arch width (p < 0.01), where BMI was not associated with alveolar bone
      morphology parameters (p > 0.01) after Bonferroni correction for multiple
      testing. CONCLUSION: Maximum bite force had a selective influence on alveolar
      thickness and shape, but not on arch width.

PMID- 19154269
TI  - Quantitative analysis of the maxilla and the mandible in hyper- and hypodivergent
      skeletal Class II pattern.
AB  - OBJECTIVES: To examine the volumetric (size) difference in the maxilla and the
      mandible of hyper- and hypodivergent skeletal patterns in Angle class II
      malocclusion. DESIGN: Descriptive retrospective study. The hypothesis is that a
      hypodivergent mandible has a larger size than a hyperdivergent mandible. SETTING
      AND SAMPLE POPULATION: Using cone-beam computed tomography, 20 subjects with
      Angle class II malocclusion were classified into two groups; 10 of 20 subjects
      formed a hyperdivergent group while the rest formed a hypodivergent group.
      MATERIAL AND METHODS: Cone-beam computed tomography images were obtained and
      processed and 3D volume data was measured by one clinician. Dahlberg's technique
      was used to assess the measurement error and significant difference was set at p
      < 0.05. RESULTS: No significant differences were found between the volumes of the
      maxilla and mandible in both groups. Differences were observed in the ratio of
      mandibular/maxillary volumes. The hypodivergent group had a significantly larger
      (p = 0.014) ratio than the hyperdivergent group. CONCLUSIONS: Maxillary and
      mandibular volumes differ between hyper- and hypodivergent skeletal patterns.

PMID- 19154270
TI  - Tenoxicam controls pain without altering orthodontic movement of maxillary
      canines.
AB  - OBJECTIVES: To study the efficacy of tenoxicam for pain control, its potential
      for preemptive analgesia, and its influence on the orthodontic movement of upper
      canine teeth. DESIGN: This was a randomized controlled double-blind cross-over
      study. The patients were divided into three groups. Two groups received tenoxicam
      in daily doses of 20 mg orally for 3 days. Group A received the first dose of the
      drug before orthodontic activation and group B, just afterwards. Group C
      (control) received a placebo for 3 days. All groups had access to 750 mg of
      paracetamol up to four times a day. Three orthodontic activations were performed
      at 30-day intervals. Each patient belonged to two different groups. Pain
      intensity was assessed using a descriptive Pain Scale and a Visual Analog Scale.
      SETTING AND SAMPLE POPULATION: Private clinic; 36 patients undergoing bilateral
      canine tooth retraction. RESULTS: The statistical analysis did not show any
      difference in movement between the active groups and the control at any time.
      There was no statistical difference between the groups that received tenoxicam.
      Pain intensity in these groups was lower than in the placebo group. The
      difference in pain intensity between the active groups and the control was
      greatest at the assessment made 12 h after activation and it tended to zero, 72 h
      after activation. CONCLUSIONS: Tenoxicam did not influence orthodontic movement
      of the upper canines. It was effective for pain control and did not present any
      preemptive analgesic effect.

PMID- 19154271
TI  - The interdental gingiva, a visible guide for placement of mini-implants.
AB  - OBJECTIVES: To determine whether the tip of the interdental gingiva can serve as
      a visible guide for placement of mini-implants. SETTING AND SAMPLE POPULATION:
      Computer tomography (CT) images from 15 males and 15 females (mean age 27 years,
      range: 23-35 years) were used to evaluate the distance from the tip of the
      interdental gingiva to the alveolar crest from the central incisor to the 1st
      molar. The distance from a reference point to the tip of interdental gingiva was
      recorded from study models using a caliper. The distance between the reference
      point and the alveolar crest was recorded using CT and added to the model
      recordings thus providing the distance from the tip of interdental gingiva to the
      alveolar crest for the various interdental sites. Two-way anova and Student
      Newman-Keuls test for multiple comparisons were used for the statistical
      analysis. RESULTS: There was no significant difference in the distance from the
      tip of interdental gingiva to the alveolar crest between maxilla and mandible.
      The distance between the tip of interdental gingiva and the alveolar crest at the
      central/lateral incisors was the shortest compared with that of other sites.
      There was also a statistically significant difference between the male and female
      groups except for the maxillary 2nd premolar/1st molar interradicular site.
      CONCLUSION: The tip of interdental gingiva appears a reasonable visual guide for
      the placement of mini-implants for orthodontic anchorage.

PMID- 19154272
TI  - Bone density at interradicular sites: implications for orthodontic mini-implant
      placement.
AB  - OBJECTIVES: Implant stability is primarily related to local bone density; Few
      studies have evaluated interradicular bone density related to mini-implant
      placement for orthodontic anchorage. Therefore, this study evaluated bone density
      differences between interradicular sites. SETTING AND SAMPLE POPULATION: Computed
      tomographic (CT) images were obtained from 14 males and 14 females (mean age 27
      years, range 23-35 years). Bone density in Hounsfield units (HU) was measured at
      13 interradicular sites and four bone levels. RESULTS: Bone densities in most
      areas were higher than 850 HU. Statistically significant differences in bone
      density were detected at different levels and sites. Bone densities in both
      maxilla and mandible significantly increased from the alveolar crest toward basal
      bone in posterior areas, while the opposite was observed in anterior areas. There
      were statistically significant differences in bone densities between the maxilla
      and mandible in posterior areas. Bone densities progressively increased from
      anterior to posterior areas in the mandible. CONCLUSION: The results suggest that
      mini-implants for orthodontic anchorage may be effective when placed in most
      areas with equivalent bone density up to 6 mm apical to the alveolar crest. Site
      selection should be adjusted according to bone density assessment.

PMID- 19154273
TI  - Reproducibility of facial soft tissue landmarks on 3D laser-scanned facial
      images.
AB  - BACKGROUND: The three-dimensional (3D) measuring technology is useful to inspect
      facial shape in three planes of space (X, Y, and Z). Recent work has been
      directed to analyse craniofacial morphology using facial soft tissue landmarks to
      identify facial differences among population. The reproducibility of facial
      landmarks is almost necessary to ensure accurate 3D facial measurements.
      OBJECTIVE: The aim of this study is to assess the reproducibility of facial soft
      tissue landmarks using laser-scan 3D imaging technology. SUBJECTS AND METHODS:
      Facial landmarks were assessed for 30 15(1/2)-year-old British-Caucasian children
      (15 males and 15 females). The sample was recruited from the Avon Longitudinal
      Study of Parents and Children (ALSPAC). The 3D facial images were acquired for
      each subject using two high-resolution Konica/Minolta laser scanners. Twenty-one
      facial landmarks (63 X, Y, and Z coordinates) were identified and recorded on
      each 3D facial image by two examiners. The reproducibility of landmarks
      identification at 2-week interval was assessed for one of the examiners (intra
      examiner). In addition, the reproducibility of landmarks was assessed between the
      two examiners (inter-examiner). Using Bland-Altman plots, both intra- and inter
      examiner assessments had evaluated landmarks reproducibility in three dimensions
      for the sample divided by gender. The reproducibility of the 3D-coordinates for
      each landmark was considered under three categories (< 0.5 mm, < 1 mm, and >1 mm)
      for both intra- and inter-examiner reproducibility assessments. RESULTS: The
      distribution of coordinates at the three levels of reproducibility show the
      following percentages: intra-examiner: < 0.5 mm (38%), < 1 mm (51%), >1 mm (11%);
      inter-examiner: < 0.5 mm (35%), < 1 mm (48%), >1 mm (17%). Generally, 10
      landmarks were reproducible to less than 1 mm for both intra- and inter-examiner
      reproducibility assessments. The Labiale Superius was the most reproducible and
      Palebrale Superius was the least reproducible landmark. Some landmarks showed
      greater reliability in certain planes of space; the Glabella was more reliable in
      the Z than the Y axis. Gender differences were found; Subnasale was more
      reproducible in the Y-axis in males compared with females. CONCLUSIONS: The
      reproducibility of facial landmarks should be considered in the three planes of
      space. The majority of X-Y-Z coordinates taken to the 21 facial landmarks were
      reproducible to < 1 mm which is clinically acceptable. The accuracy of landmarks
      identification ranged from 0.39 to 1.49 mm. The reliability in identification
      depends on the clarity and definition of each landmark as well as gender
      characteristics. The different landmarks reproducibility should be considered
      when evaluating changes related to growth and healthcare interventions.

PMID- 19154274
TI  - In-vitro evaluation of the corrosion behavior of orthodontic brackets.
AB  - OBJECTIVE: The number of bracket systems for orthodontic therapy increases
      significantly. One major concern of newly developed orthodontic devices is
      aspects of corrosion and biocompatibility. MATERIAL AND METHODS: In this study,
      nine bracket systems made of different material and from various design
      principles were tested with respect to their corrosion behavior. Electrochemical
      and static immersion tests with subsequent measurement of nickel ion release were
      performed. In addition surface alterations of the brackets after corrosion were
      documented by scanning electron microscopy. Studies of corrosion behavior were
      performed according to the DIN/ISO standard 10271 for corrosion testing of dental
      materials. RESULTS: All systems showed traces of corrosion after electrochemical
      testing. However, after static immersion testing only minor corrosion defects
      could be documented and the measured nickel ion release was far below critical
      limits. CONCLUSIONS: All tested systems seem to be biocompatible and applicable
      for orthodontic therapy. The measured nickel values are far below the daily
      dietary intake level. A static immersion test combined with the nickel ion
      release measurement seems to be more relevant for the determination of
      biocompatibility than the electrochemical testing.

PMID- 19154275
TI  - Optical dispensing: the science of vision or blind faith?
AB  - The evidence for the basic optometric function of optical dispensing is discussed
      in terms of the basic principles of scientific debate. The degree of rigour
      applied to product testing and evaluation of most other medically related areas
      is lacking in the dispensing of spectacles. There has been much debate on the
      place of religious faith in our society. Religious belief masquerading as science
      has come in for particular scrutiny. However, little attention has been paid to
      the equally contentious issue of non-religious belief, within scientific
      disciplines, masquerading as science. It could be argued that optical dispensing
      is, to a significant degree, such a case.

PMID- 19154276
TI  - A critical evaluation of the evidence supporting the practice of behavioural
      vision therapy.
AB  - In 2000, the UK's College of Optometrists commissioned a report to critically
      evaluate the theory and practice of behavioural optometry. The report which
      followed Jennings (2000; Behavioural optometry--a critical review. Optom. Pract.
      1: 67) concluded that there was a lack of controlled clinical trials to support
      behavioural management strategies. The purpose of this report was to evaluate the
      evidence in support of behavioural approaches as it stands in 2008. The available
      evidence was reviewed under 10 headings, selected because they represent patient
      groups/conditions that behavioural optometrists are treating, or because they
      represent approaches to treatment that have been advocated in the behavioural
      literature. The headings selected were: (1) vision therapy for
      accommodation/vergence disorders; (2) the underachieving child; (3) prisms for
      near binocular disorders and for producing postural change; (4) near point stress
      and low-plus prescriptions; (5) use of low-plus lenses at near to slow the
      progression of myopia; (6) therapy to reduce myopia; (7) behavioural approaches
      to the treatment of strabismus and amblyopia; (8) training central and peripheral
      awareness and syntonics; (9) sports vision therapy; (10) neurological disorders
      and neuro-rehabilitation after trauma/stroke. There is a continued paucity of
      controlled trials in the literature to support behavioural optometry approaches.
      Although there are areas where the available evidence is consistent with claims
      made by behavioural optometrists (most notably in relation to the treatment of
      convergence insufficiency, the use of yoked prisms in neurological patients, and
      in vision rehabilitation after brain disease/injury), a large majority of
      behavioural management approaches are not evidence-based, and thus cannot be
      advocated.

PMID- 19154277
TI  - The quality of optometrists' referral letters for glaucoma.
AB  - PURPOSE: The purpose of the study was to evaluate the quality of content of
      optometrist-initiated glaucoma referral letters arriving at the appointment
      booking centre at Moorfields Eye Hospital (MEH). METHODS: The minimum standard of
      information required for an ophthalmologist to determine the appropriateness and
      urgency of glaucoma suspect referral was determined, and criteria for three
      standards of referral letter formulated: 'Ideal', 'Acceptable' and 'Fail'. These
      standards were applied to a prospective review of all optometrist-derived
      referrals for glaucoma or suspected glaucoma cases arriving in the MEH booking
      centre over a 4-month period. The contents of each letter were scrutinised and
      classified based on the criteria within each standard. RESULTS: Forty-nine per
      cent of referral letters were found to be of 'acceptable' quality, 7%'ideal'
      quality and the remainder classed as "fail". The main reason for failure was an
      omission of non-clinical information, including patient and/or referring practice
      details, although 26% of letters failed to include an optic disc evaluation and
      6% failed to provide intra-ocular pressure measurements. Two-thirds of
      'acceptable' letters did not reach the 'ideal' standard due to a lack of
      discussion of risk factors, visual field analysis or recommendations for referral
      speed. DISCUSSION: The information gleaned from this prospective study indicates
      a need to improve the quality of optometrists' glaucoma referral letters,
      particularly with respect to completion of all the items set out on the General
      Ophthalmic Services (GOS) 18 referral form.

PMID- 19154278
TI  - Referrals to ophthalmology: optometric and general practice comparison.
AB  - PURPOSE: To assess referrals from primary care practitioners to an
      ophthalmological practice in order to determine whether any differences exist
      between the two primary care groups in the types of conditions referred, and in
      concurrence between reasons for referral and ophthalmological diagnosis. METHODS:
      This study investigated patient referrals from general practitioners and
      optometrists to an ophthalmologist's practice in Belfast, over a period of 3
      months from January 2007 to the end of March 2007. Anonymised data were divided
      into two groups depending on the referring practitioner. Within the two groups,
      patient numbers were sub-divided into 15 categories covering the range of
      diagnoses made. Preliminary diagnoses or reasons for referral were compared with
      the definitive diagnoses made by the ophthalmologist. RESULTS: Optometrists
      contributed the greatest number of referrals (323) with 243 patients referred by
      general practitioners. Cataract was the most common condition referred by
      optometrists, and the second most common condition referred by general
      practitioners: agreement with ophthalmological diagnosis was high for both groups
      of primary care practitioners. Concurrence of referral reason with
      ophthalmological diagnosis for glaucoma was lower for general practitioners (56%)
      than for optometrists (76%), but optometrists referred more false positive
      patients for glaucoma than did general practitioners. The opposite was true for
      lid/tear duct/conjunctival conditions, the most common basis for referral by
      general practitioners. CONCLUSIONS: The differences between the two primary care
      practitioner groups may reflect variations in training, skills and practice.
      Further investigation of the particular strengths of both groups, and how they
      can be optimised to promote effective shared care, is required.

PMID- 19154279
TI  - The effectiveness of progressive addition lenses on the progression of myopia in
      Chinese children.
AB  - PURPOSE: To evaluate the effectiveness of progressive addition lenses (PALs),
      with a near addition of +1.50 D, on the progression of myopia in Chinese
      children. METHODS: We enrolled 178 Chinese juvenile-onset acquired myopes (aged 7
      13 years, -0.50 to -3.00 D spherical refractive error), who did not have
      moderately or highly myopic parents, for a 2-year prospective study. They were
      randomly assigned to the PAL group or single vision (SV) group. Primary
      measurements, which included myopia progression and ocular biometry, were
      performed every 6 months. Treatment effect was adjusted for important covariates,
      by using a multiple linear regression model. RESULTS: One hundred and forty-nine
      subjects (75 in SV and 74 in PAL) completed the 2-year study. The myopia
      progression (mean +/- S.D.) in the SV and PAL groups was -1.50 +/- 0.67 and -1.24
      +/- 0.56 D, respectively. This difference of 0.26 D over 2 years was
      statistically significant (p = 0.01). The lens type (p = 0.02) and baseline
      spherical equivalent refraction (p = 0.05) were significant contributing factors
      to myopia progression. Mean increase in the depth of vitreous chamber was 0.70 +/
      0.40 and 0.59 +/- 0.24 mm, respectively. This difference of 0.11 mm was
      statistically significant (p = 0.04). Age (p < 0.01) was the only contributing
      factor to the elongation of vitreous chamber. Different near phoria (p < 0.01)
      and gender (p = 0.02) caused different treatment effects when wearing SV lenses.
      However, there were no factors found to influence the treatment effect of wearing
      PALs. CONCLUSIONS: Compared with SV lenses, myopia progression was found to be
      retarded by PALs to some extent in Chinese children without moderately or highly
      myopic parents, especially for subjects with near esophoria or females.

PMID- 19154280
TI  - Soft contact lens cleaning: rub or no-rub?
AB  - PURPOSE: To compare effectiveness of cleaning with and without rubbing of soft
      contact lenses. METHODS: Three-hundred new biweekly disposable hydrogel lenses
      (Ocufilcon D, FDA Group IV; 55% water content) were artificially deposited with
      serum albumin, hand cream (semi-transparent deposits) and mascara (black
      deposits). The treated lenses were randomly divided into three groups, each group
      cleaned by one of three methods of cleaning--Rubbing (R), No-Rub following the
      manufacturer's instruction on duration of rinsing (NR1) and No-Rub with a shorter
      duration of rinsing (NR2). Four commercially-available multipurpose solutions
      (MPS) and a saline were used. The cleaning effectiveness was determined by the
      amount of deposits remaining on the contact lenses after cleaning, assessed with
      the aid of a slit-lamp. The level of deposits remaining (in terms of coverage of
      lens surface) were determined using a five-point scale [0 (no observable
      deposits)--4 (>80% deposits remained)] for semi-transparent deposits (protein and
      hand cream) and black deposits (mascara). The investigators were masked as to the
      solutions used (except for one MPS which has a different rinsing time than the
      other MPS), and the investigator who assessed the deposits left on the lenses did
      not know which solution or cleaning method was used to clean each lens. RESULTS:
      Lenses cleaned by the R method were significantly cleaner than those cleaned by
      methods NR1 and NR2. No significant difference was found between lenses cleaned
      by NR1 and NR2 methods. The median grade of deposits for lenses cleaned by R
      method was 0.5 for both semi-transparent and black deposits. For lenses cleaned
      by NR1 and NR2 methods, the median grade of deposits left on lens surfaces was
      4.0 for both types of deposits. Different solutions used did not affect the level
      of deposits left on lens surfaces for all three cleaning methods. CONCLUSIONS:
      Not rubbing the soft lens when cleaning is ineffective in removing loosely-bound
      deposits. A longer rinse, as recommended by the manufacturers, does not remove
      significantly more deposits than a shorter rinse with the MPS. This work supports
      the view that contact lens wearers should be encouraged to rub their lenses when
      cleaning.

PMID- 19154281
TI  - Age-related paraxial schematic emmetropic eyes.
AB  - Based on recent biometric data, four-surface paraxial schematic emmetropic eyes
      for different ages have been developed. There are three sets of schematic eyes:
      male, female and overall. With increase in age, the changes in the schematic eyes
      are decreased anterior chamber depth, increased lens thickness, decreased
      vitreous length, increased axial length, decreased anterior lens radius of
      curvature and increased lens equivalent refractive index. Gender differences are
      greater anterior corneal radii of curvature (0.07 mm), longer vitreous chambers
      (0.70 mm), longer axial length (0.70 mm) and lower lens equivalent refractive
      indices of male eyes (0.007) relative to female eyes. Gaussian parameters of the
      various schematic eyes are given.

PMID- 19154282
TI  - The effect of altering spherical aberration on the static accommodative response.
AB  - PURPOSE: To investigate the effect of altering the spherical aberration (SA) of
      the eye on the static accommodative response. METHODS: Participants were fitted
      with nominally afocal contact lenses with controlled amounts of SA of either 
      0.2, -0.1, 0.0, +0.1 or +0.2 microm for a 5-mm pupil. Measurements of SA and root
      mean square (RMS) total aberration for the eye plus lens for each participant
      were determined with a Complete Ophthalmic Analysis System aberrometer.
      Accommodation was stimulated either by placing targets at different dioptric
      distances from the eye, or by using a fixed distance target and placing negative
      powered lenses in front of the eye. Accommodation responses were determined with
      a Shin-Nippon autorefractor. RESULTS: For both stimuli situations, the slope of
      the accommodation stimulus-response function was lowest for the lenses with +0.2
      microm SA, and increased as the amount of SA was reduced. There was a significant
      negative correlation between SA and slope. Lag of accommodation at 33 cm
      correlated well with added SA, but did not correlate with total RMS error. There
      was no significant difference between the responses at 30 min after lens wear
      started and the responses after 1 h. CONCLUSIONS: Adding negative SA to the eye
      generally improves the slope of the accommodation stimulus-response curve and
      decreases lag of accommodation, and positive added SA depresses the slope of the
      stimulus-response curve and increases lag. The effect seems to be specific to SA,
      as there was no relationship between lag and RMS error. Altering SA may be a
      viable way of changing accommodative functions in clinical situations.

PMID- 19154283
TI  - Accommodation, pupil diameter and myopia.
AB  - Concurrent measurements of steady-state accommodation response/stimulus curves
      and of pupil diameter were made in groups (n = 20) of young, adult myopes [age
      (mean +/- SD) 23.1 +/- 4.5 years, mean-sphere error (MSE) -3.06 +/- 2.35 D, range
      -0.60 to -8.54 D] and emmetropes (mean age 25.3 +/- 5.7 years, mean MSE -0.07 +/-
      0.26 D, range -0.50 to +0.50 D). The aim of this study was to explore the
      possibilities that pupil diameters with relaxed accommodation were larger, and
      that accommodative miosis was weaker, in the myopic group. Such behaviour would
      lead to relatively greater degradation of the retinal images in the myopic group,
      even though aberrations at constant pupil diameter and dioptric accommodative
      lags in the two groups were the same: this might result in excessive axial growth
      and further myopia development. No evidence for any systematic refractive
      dependence of pupillary characteristics or accommodative responses was found.
      Interestingly, those subjects whose response/stimulus curves had a higher slope
      tended to display greater accommodative miosis, irrespective of their refractive
      error.

PMID- 19154284
TI  - Reconstructing ocular surfaces by Purkinje images: an exact ray approach.
AB  - A method originally developed for corneal topography (using discrete sources and
      Zernike polynomials) was extended to estimate the geometry of ocular surfaces
      internal to the eye. The approach was tested in simulation as a candidate method
      for phakometry. Purkinje images from the anterior surface of an intra-ocular lens
      (IOL) (aligned and decentered) were simulated using the Navarro eye. The 'full'
      Navarro eye and a simplified eye were assumed for recovery purposes. Root mean
      square (RMS) errors and (anterior) IOL radii of curvatures (best-fit spheres)
      were estimated. The robustness of the method to axial shifts in lens position
      (both eye models) along with assumed refractive index (simplified eye only) was
      tested. When axial shifts were ignored, RMS errors for the full eye were sub
      micron (<0.8 microm), and radii of curvature errors were approximately 1 microm.
      Axial shifting increased these errors linearly. The n = 1.32 error curve
      (simplified eye) matched the full eye error curves closely (for both RMS error
      and IOL lens radius), although the RMS error curve exhibited some asymmetry for a
      decentered IOL. The nominal refractive index (n = 1.3305) was sub-optimal in all
      cases. The resulting method is a potentially useful way to estimate the geometry
      of the internal ocular surfaces.

PMID- 19154285
TI  - Does binocularly perceived depth correlate with reduced stereoacuity?
AB  - AIM: To assess perceived depth in the Wirt Fly Stereotest for assessing
      stereoacuity. METHODS: Somers and Hamilton [Ophthalmic Physiol. Opt. 4 (1984)
      245] reported a strong correlation for four observers with normal vision, between
      perceived depth in the Wirt Fly stereotest and degradation of Keystone
      stereothresholds from induced anisometropia created using a range of monocular
      plus lenses. Depth was measured with a pointer placed by subjects alongside the
      tip of the Fly's wing. Our study replicated that of Somers and Hamilton, but with
      several methodological refinements (mainly, use of a headrest to control head
      position) and more subjects. RESULTS: We confirm Somers and Hamilton's results
      for normal observers by finding (1) induced anisometropia causes systematic depth
      reduction for the Fly and (2) significant correlations between fly depth and
      stereothresholds (as measured with the Frisby Near and the Randot Circles
      stereotests). However, the mean values mask considerable between subject
      variation in responses. CONCLUSION: The substantial individual and between
      subject variation in Wirt Fly perceived depth causes us to doubt its value as a
      proxy for stereoacuity except as a rough estimate.

PMID- 19154286
TI  - Determining the zone of reflection for posterior corneal surface comparison
      phakometry.
AB  - Although comparison phakometry has been used by a number of studies to measure
      posterior corneal shape, these studies have not calculated the size of the
      posterior corneal zones of reflection they assessed. This paper develops paraxial
      equations for calculating posterior corneal zones of reflection, based on
      standard keratometry equations and equivalent mirror theory. For targets used in
      previous studies, posterior corneal reflection zone sizes were calculated using
      paraxial equations and using exact ray tracing, assuming spherical and aspheric
      corneal surfaces. Paraxial methods and exact ray tracing methods give similar
      estimates for reflection zone sizes less than 2 mm, but for larger zone sizes ray
      tracing methods should be used.

PMID- 19154287
TI  - Obesity reviews--now the number one journal in nutrition and obesity.

PMID- 19154291
TI  - Identity and difference in health and healthcare.

PMID- 19154292
TI  - Constructing a 'plausible narrative of progress' for nursing: a neopragmatist
      suggestion.
AB  - Identity, difference, and the associated subject of cultural diversity pose
      challenges for nursing. As the demographics of the world change, demands are
      rising for nurses to provide sensitive, individualized care to people living in
      our ever-changing global community. Issues concerning gender, sexuality,
      disability, age, language, economic and occupational status, multiculturalism,
      and ethnicity are made more complex because many of these topics strike a
      personal chord for individual nurses. In order for nursing to provide appropriate
      care to the world's people and to meet future challenges, nursing must define
      itself in new ways. Kikuchi and Simmons have stated that the best way for nursing
      to approach this task is through the development of a 'sound' philosophy of
      nursing that will 'accommodate diversity in nursing thought'. They contend that
      before we can establish a philosophy of nursing, nurses will have to agree upon
      the nature of reality, human beings, truth, and knowledge. This paper will
      suggest that neopragmatism, as described by Richard Rorty, is a way to assure
      diversity of thought in nursing. However, I will argue against the requirement
      for this philosophy to be 'sound' in the sense that Kikuchi and Simmons use this
      term. In place of their call for 'truth and unity in nursing thought'. I will
      attempt to demonstrate how neopragmatic ideas relate to the construction of what
      Rorty called a unifying 'plausible narrative of progress'. This change will allow
      nursing to abandon the dead end debate over epistemologies and instead focus on
      more important issues related to improving nursing practice.

PMID- 19154293
TI  - Examining the conflation of multiculturalism, sexism, and religious
      fundamentalism through Taylor and Bakhtin: expanding post-colonial feminist
      epistemology.
AB  - In this post-9/11 era marked by religious and ethnic conflicts and the rise of
      cultural intolerance, ambiguities arising from the conflation of
      multiculturalism, sexism, and religious fundamentalism jeopardize the delivery of
      culturally safe nursing care to non-Western populations. This new social reality
      requires nurses to develop a heightened awareness of health issues pertaining to
      racism and ethnocentrism to provide culturally safe care to non-Western
      immigrants or refugees. Through the lens of post-colonial feminism, this paper
      explores the challenge of providing culturally safe nursing care in the context
      of the post-9/11 in Canadian healthcare settings. A critical appraisal of the
      literature demonstrates that post-colonial feminism, despite some limitations,
      remains a valuable theoretical perspective to apply in cultural nursing research
      and develop culturally safe nursing practice. Post-colonial feminism offers the
      analytical lens to understand how health, social and cultural context, race and
      gender intersect to impact on non-Western populations' health. However, an
      uncritical application of post-colonial feminism may not serve racialized men's
      and women's interests because of its essentialist risk. Post-colonial feminism
      must expand its epistemological assumptions to integrate Taylor's concept of
      identity and recognition and Bakhtin's concepts of dialogism and unfinalizability
      to explore non-Western populations' health issues and the context of nursing
      practice. This would strengthen the theoretical adequacy of post-colonial
      feminist approaches in unveiling the process of racialization that arises from
      the conflation of multiculturalism, sexism, and religious fundamentalism in
      Western healthcare settings.

PMID- 19154294
TI  - 'The demented other': identity and difference in dementia.
AB  - This paper explores the impact of the concepts of identity and difference on
      demented persons (especially on persons with Alzheimer's disease). The diagnosis
      of dementia is often synonymous with the assertion that demented individuals are
      no longer capable of making reasonable decisions. But rationality is an important
      aspect of characterizing a person's identity. Hence, this prevailing image of
      dementia as a loss of self and a change of identity leads to the situation that
      demented persons represent difference and otherness. Here, the brain and the mind
      act as the source for difference. The paper discusses several identity concepts
      with regard to demented persons and the relationship between identity and
      difference in dementia. This analysis is accompanied by an examination of the
      current biopolitics of dementia and ageing as biopolitics constitutes the socio
      political-medical understanding of dementia. Challenges and possibilities for
      dementia care will be explored in the context of this complex relationship
      between theoretical concepts and political, medical, and health-care practices.

PMID- 19154295
TI  - La difference: condition of exclusion or of reconnaissance?
AB  - From the Middle Ages onto the 19th century, following the trend set in leper
      hospitals, madness was to be hidden, secluded in dark places, far away from the
      mainstream of society. The emergence of the mad person, perceived as inevitably
      different, allows to make the boundaries between reason and folly, between human
      and inhuman, irrelevant. If leper hospitals have almost emptied out, if there are
      much fewer confinement facilities, the values and images related to the leper or
      the mad person, as well as the sense of exclusion, continue to persist. The
      purpose of this paper is to show clearly that this matter of exclusion is a
      serious legacy that could very well apply nowadays to other figures that, each in
      their own way, symbolize menace or mockery. It applies notably to the aged and
      the dying who both appear as the opposite of modern society and its values of
      efficiency, productivity and profitability. The multiplication of places where
      old people are left to die, and the elderly who are crowded in old folks homes,
      stand as proof of their exclusion from society. Nevertheless, youth and old age
      coexist, as well as life and death. If care of others is the trait of a humane
      civilization, must it be understood that barbarism consists in ignoring its own
      humanity as well as that of others? In view of such practices of exclusion,
      policy statements based on recognition of human dignity, where ethical obligation
      rests on recognition of others and humanism, are rather paradoxical. Is this a
      paradox or a deadlock; a condition of exclusion or of reconnaissance?

PMID- 19154296
TI  - Manufacturing disability: HIV, women and the construction of difference.
AB  - In 1998, the US Supreme Court first held that asymptomatic HIV infection
      constituted a disability when it ruled on the case of Bragdon v. Abbott. The use
      of yet another label (disabled) to identify women living with HIV has been rarely
      (if ever) questioned. While we do value the use of this label as an anti
      discriminatory strategy, we believe that there is a need to examine how language
      and more specifically, the use of words such as disability, limitation, and
      impairment may create new forms of identities for women living with HIV. Using
      this legal case as a starting point, the goal of this paper is to critically
      examine the 'fabrication' of asymptomatic HIV infection as a disability. Grounded
      in a feminist poststructuralist perspective, this paper exposes the relationship
      between language, social institutions, subjectivity, and power in the
      construction of difference. By doing so, it addresses the identification of women
      living with HIV/AIDS as disabled and the self-differentiation process that they
      must go through in order to live as normally as possible.

PMID- 19154297
TI  - Doomed to fail: the persistent search for a modernist mental health nurse
      identity.
AB  - The perennial issue of the distinctiveness of the mental health nurse (MHN) is
      once again to the fore. Previous attempts to resolve this apparent identity
      crisis in the discipline have included proposals for new models, new research and
      new educational preparation as well as new alliances, and new ways of practising.
      Now the politically driven concept of the generic nurse is gaining enough
      momentum to potentially end the discussion once and for all. This paper takes a
      postmodernist approach to MHN identity that questions the requirement for MHNs to
      articulate their distinctiveness, and offers alternative constructions of this
      identity to those promulgated by policy makers and by other health disciplines.

PMID- 19154298
TI  - Intimacy, caring, and an ethics of care.

PMID- 19154304
TI  - 2020--Clinical Academic Careers: implications for critical care nursing.

PMID- 19154305
TI  - Developing and setting up a patient and relatives intensive care support group.
AB  - AIM: The purpose of this article was to highlight the need to provide support for
      patients and relatives following critical illness and discharge from hospital and
      how this can be improved through the establishment of user support groups.
      BACKGROUND: Critical illness predisposes patients to extended physical and
      psychological ill health with the potential for a reduced quality of life. The
      authors' personal experience, patient feedback and current literature suggested
      that there was a need for further support during their recovery. METHODS:
      Building on an existing formal follow-up service, Intensive Care Unit (ICU)
      Support Team for Ex-Patients established a patient-centred forum, where patients
      and relatives could share experiences with others who had also been through
      critical illness by holding drop-in sessions. Feedback from those attending these
      flexible and informal sessions indicates that support was needed and that
      patients and families have found benefit in sharing experiences with others who
      can empathise, having been through critical illness themselves. CONCLUSIONS: Our
      experience has shown there is a need that can be met simply with minimal
      investment of time and funding but that addresses a gap in patient support that
      otherwise goes unmet. Although this was a service development in one local area,
      it could be adapted to ICU patients and relatives more widely.

PMID- 19154306
TI  - Acute care teaching in the undergraduate nursing curriculum.
AB  - AIM: To incorporate basic aspects of acute care into the undergraduate nursing
      programme by providing an opportunity for the development of knowledge and skills
      in the early recognition and assessment of deteriorating patients on general
      hospital wards. BACKGROUND: Acute care initiatives implemented in the hospital
      setting to improve the identification and management of 'at risk' patients have
      focused on the provision of education for trained or qualified staff. However, to
      ensure student nurses are 'fit to practice' at the point of registration, it has
      been recommended that acute care theory and skills are incorporated into the
      undergraduate nursing curriculum. PRACTICE DEVELOPMENT INITIATIVE: An 'Integrated
      Nursing Care' module was incorporated into year 3 of the undergraduate nursing
      programme to introduce students to acute care theory and practice. Module content
      focuses on the early detection and management of acute deterioration in patients
      with respiratory, cardiac, neurological or renal insufficiencies. We used a
      competency-based framework to ensure the application of theory to practice
      through the use of group seminars. High-fidelity patient-simulated clinical
      scenarios were a key feature. The United Kingdom Resuscitation Council
      Intermediate Life Support course is also an important component of the module.
      CONCLUSIONS: Incorporating the Integrated Nursing Care module into the
      undergraduate nursing curriculum provides pre-registration students the
      opportunity to develop their knowledge and skills in acute care. RELEVANCE TO
      CLINICAL PRACTICE: The provision of undergraduate education in care of the
      acutely ill patient in hospital is essential to improve nurses' competence and
      confidence in assessing and managing deteriorating patients in general wards at
      the point of registration.

PMID- 19154307
TI  - The consultative process used in outreach: a narrative account.
AB  - AIM: The aim of this paper was to provide a narrative account of the
      communication skills used in an effective outreach consultation utilizing
      Neighbour's consultative model. Other consultation models were considered;
      however, because of their overly comprehensive approach or emphasis on behaviour
      modification, these were deemed inappropriate. BACKGROUND: The nursing profession
      has endured significant changes of late and as a result is developing more
      autonomous roles in both the community and the acute health care settings. In the
      past, the term consultancy was used within the medical context; nowadays, there
      are advance nurse practitioners for whom consultancy is an integral part of their
      role. Although every nursing interaction is in essence a consultation, the fact
      that nurses are taking up on new advanced roles highlights the necessity for
      nurses to develop their consultation skills even further. Therefore, it makes
      sense to explore what aspects of that consultancy role needs special
      consideration in order to ensure that positive outcomes are achieved.
      CONCLUSIONS: This paper has used a narrative account to uncover those salient
      skills needed to enhance the therapeutic relationship with a patient requiring
      the services of outreach. Furthermore, the application of a recognized
      consultation model was used to elucidate the underpinning knowledge of systematic
      history taking and assessment as well as demonstrating the communication skills
      and strategies needed to increase the patient's participation and empowerment
      throughout the consultation. RELEVANCE TO CLINICAL PRACTICE: Effective
      communication skills encompassed in a consultative model are integral to the
      success in safeguarding the well-being of patients requiring advanced levels of
      care. Prejudging or pre-empting information being conveyed can be detrimental to
      patient safety and may prolong or complicate treatment plans.

PMID- 19154308
TI  - Opioid and benzodiazepine withdrawal syndromes in the paediatric intensive care
      unit: a review of recent literature.
AB  - AIMS AND OBJECTIVES: This paper aims to critically review and analyse available
      literature to inform and advance patient care. BACKGROUND: Withdrawal syndromes
      related to the routine administration of sedation and analgesia in paediatric
      intensive care unit (PICU) have been recognized since the 1990 s. Common symptoms
      include tremors, agitation, inconsolable crying and sleeplessness. SEARCH
      STRATEGIES: A critical review was undertaken to assess developments in this area.
      Four databases were searched using Ovid Online. These were Ovid Medline, CINAHL,
      BNI and Embase. Key terms included were 'Paediatric', 'Sedation', 'Withdrawal'
      and 'Intensive care'. INCLUSION AND EXCLUSION CRITERIA: Articles from 1980
      onwards were reviewed for their relevance to paediatric iatrogenic withdrawal.
      Additionally, seminal work from the 1970s was included. Because of the scarcity
      of literature, relevant editorials and opinion pieces were included. RESULTS: A
      total of 2,232,586 papers resulted from keyword searches. Use of Boolean
      operators to combine terms reduced the number of results to 62. Exclusion
      criteria reduced the number of suitable papers to 20. Tracking reference lists
      yielded a further 18 papers. In total, 38 papers were retrieved examining 1375
      patients. Four papers surveyed drug usage on PICU, 14 listed withdrawal symptoms,
      4 described the frequency of withdrawal in the PICU population, 9 described risk
      factors, 4 presented or validated clinical tools and 14 describe treatment
      strategies. CONCLUSIONS: Withdrawal syndromes may affect 20% of exposed children
      and are related to infusion duration and total dose. Fifty-one symptoms are
      described in the literature. Future studies need accurate, validated clinical
      tools to be effective. Risk factors, signs and symptoms have been identified, and
      validation studies must now take place. RELEVANCE TO CLINICAL PRACTICE:
      Withdrawal syndromes continue to be widespread and difficult to diagnose.
      Awareness of their causes and treatments should influence clinical decisions at
      the bedside.

PMID- 19154309
TI  - Commentary: Munro CL et al. (2006). Oral health status and development of
      ventilator-associated pneumonia: a descriptive study.

PMID- 19154311
TI  - Specialist Library for Surgery, Theatres and Anaesthesia expanding into critical
      care.

PMID- 19154314
TI  - Long bugs to short plants--the Lon protease in protein stability and
      thermotolerance.

PMID- 19154315
TI  - Which of these continents is not like the other? Comparisons of tropical savanna
      systems: key questions and challenges.

PMID- 19154316
TI  - Can biological invasions induce desertification?

PMID- 19154317
TI  - Plant responses to photoperiod.
AB  - Photoperiod controls many developmental responses in animals, plants and even
      fungi. The response to photoperiod has evolved because daylength is a reliable
      indicator of the time of year, enabling developmental events to be scheduled to
      coincide with particular environmental conditions. Much progress has been made
      towards understanding the molecular mechanisms involved in the response to
      photoperiod in plants. These mechanisms include the detection of the light signal
      in the leaves, the entrainment of circadian rhythms, and the production of a
      mobile signal which is transmitted throughout the plant. Flowering, tuberization
      and bud set are just a few of the many different responses in plants that are
      under photoperiodic control. Comparison of what is known of the molecular
      mechanisms controlling these responses shows that, whilst common components
      exist, significant differences in the regulatory mechanisms have evolved between
      these responses.

PMID- 19154318
TI  - Oxygen stable isotope ratios of tree-ring cellulose: the next phase of
      understanding.
AB  - Analysis of the oxygen isotope ratio of tree-ring cellulose is a valuable tool
      that can be used as a paleoclimate proxy. Our ability to use this tool has gone
      through different phases. The first began in the 1970s with the demonstration of
      empirical relationships between the oxygen isotope ratio of tree-ring cellulose
      and climate. These empirical relationships, however, did not provide us with the
      confidence that they are robust through time, across taxa and across geographical
      locations. The second phase began with a rudimentary understanding of the
      physiological and biochemical mechanisms responsible for the oxygen isotope
      ratios of cellulose, which is necessary to increase the power of this tool. This
      phase culminated in a mechanistic tree-ring model integrating concepts of
      physiology and biochemistry in a whole-plant system. This model made several
      assumptions about leaf water isotopic enrichment and biochemistry which, in the
      nascent third phase, are now being challenged, with surprising results. These
      third-phase results suggest that, contrary to the model assumption, leaf
      temperature across a large latitudinal gradient is remarkably constant and does
      not follow ambient temperature. Recent findings also indicate that the
      biochemistry responsible for the incorporation of the cellulose oxygen isotopic
      signature is not as simple as has been assumed. Interestingly, the results of
      these challenges have strengthened the tree-ring model. There are several other
      assumptions that can be investigated which will improve the utility of the tree
      ring model.

PMID- 19154319
TI  - Factors driving distribution limits in an annual plant community.
AB  - Studies examining plant distribution patterns across environmental gradients have
      generally focused on perennial-dominated systems, and we know relatively little
      about the processes structuring annual communities. Here, the ecological factors
      determining local distribution patterns of five dominant annual species
      distributed across micro-topographic gradients in ephemeral California wetlands
      are examined. Over two growing seasons in three vernal pools, patterns of
      inundation and above-ground biomass were characterized across the
      microtopographic gradient, population boundaries for five dominant species were
      documented and a reciprocal transplant experiment and neighbor removal treatment
      were conducted to test the relative effects of within-pool elevation, competition
      and seed dispersal on plant performance. Despite large differences in inundation
      time between growing seasons, above-ground biomass and the elevation of
      population boundaries remained consistent. The predicted 'optimal' depth for each
      species shifted between years, but competition and recruitment limitation
      restricted species' abilities to track these conditions. The distributions of the
      focal taxa are primarily driven by differential responses to environmental
      conditions associated with different microtopographic positions along pool
      inundation gradients, and are reinforced by competition and dispersal
      constraints. The relative importance of competition, other environmental factors
      and dispersal patterns appear to contrast with results obtained in systems
      dominated by perennial plants.

PMID- 19154320
TI  - Oxidative stress in developmental brain disorders.
AB  - Oxidative stress is one of the predisposing factors in adult neurological
      disorders. We have examined the involvement of oxidative stress in child-onset
      neurodegenerative disorders, and here we review the findings from our analysis.
      In cases of Cockayne syndrome, the oxidative products of lipids and proteins were
      increased in the globus pallidus; however, oxidative nucleotide damage that
      coincided with reduced copper/zinc superoxide dismutase (Cu/ZnSOD) expression was
      observed in cases of xeroderma pigmentosum, and these patients also presented
      increased oxidative stress markers in urine samples. In spinal muscular atrophy,
      lipid peroxidation in conjunction with oxidative DNA damage was observed in motor
      neurons. Cases of subacute sclerosing panencephalitis presented oxidative
      nucleoside damage in cerebral cortical neurons at early disease stages, which
      were subsequently replaced by lipid peroxidation in glial cells of cerebral white
      matter. In relation to progressive myoclonic epilepsy, oxidative damage to DNA,
      proteins, and lipids appeared to coincide with cerebral and cerebellar cortical
      lesions of neuronal ceroid-lipofuscinosis. Patients with Lafora disease also
      presented an increase in oxidative stress markers for DNA and/or lipids in the
      brain and urine. These findings imply involvement of oxidative stress in
      developmental brain disorders; antioxidant agents could prove to be useful for
      treating patients with those disorders.

PMID- 19154321
TI  - Comparison of the Mayo Clinic Quadratic Equation with the Modification of Diet in
      Renal Disease equation and radionuclide glomerular filtration rate in a clinical
      setting.
AB  - BACKGROUND: Recent guidelines recommend automatic reporting of estimated
      glomerular filtration rate (eGFR) using the abbreviated Modification of Diet in
      Renal Disease (MDRD) equation with every request for plasma creatinine. The Mayo
      Clinic Quadratic Equation (MCQE) has been put forwards as a potentially more
      accurate alternative. We therefore evaluated its accuracy compared with
      radionuclide GFR in a clinical setting. METHOD: Data were collected on 601
      patients aged 16-85 years who had undergone radionuclide GFR, and eGFR was
      calculated using MCQE and MDRD. Calculations of bias, correlation coefficients
      and percentage estimates within 30% and 50% of radionuclide GFR were used in
      comparisons. RESULTS: The MCQE had a significant positive bias in the overall
      population but no significant bias in individuals with normal renal function
      defined as measured GFR > 90 mL/min per 1.73 m(2). There was no significant
      difference in the performance of MCQE and MDRD eGFR in patients with measured GFR
      > 90 mL/min per 1.73 m(2). However, in the overall group and in subjects with
      radionuclide GFR < 90 mL/min per 1.73 m(2), the accuracy of MDRD eGFR with
      respect to the proportion of patients within 30% and 50% of radionuclide GFR was
      better than MCQE. CONCLUSION: MCQE compared moderately well with radionuclide
      GFR, although its overall bias and accuracy were inferior when compared with the
      MDRD equation in a clinical setting.

PMID- 19154322
TI  - Function of dynamically stimulated endothelium and renin-angiotensin-aldosterone
      system in normotensive subjects with a family history of hypertension.
AB  - AIM: Genetic influences on the acute stimulation of the renin-angiotensin
      aldosterone system (RAAS) and on endothelial activation were studied by examining
      healthy blood donors with and without hypertensive parents. METHODS: Healthy
      blood donors were assigned to two groups, according to the presence or absence of
      a parental history of hypertension. Plasma levels of renin, nitric oxide (NO) and
      plasminogen activator inhibitor 1 (PAI-1) were studied before and after acute
      alterations in renal perfusion induced by phlebotomy, and the two groups
      compared. During phlebotomy, 400-500 mL of blood was extracted from each subject,
      with that volume varying relative to each subject's body surface area (m(2)).
      RESULTS: No statistically significant inter-group differences were observed
      between the baseline mean levels of plasma renin, NO or PAI-1. After phlebotomy,
      significant increases were detected in mean plasma renin activity (PRA) and NO
      levels and in PAI-1 activity (P < 0.001). However, the increases in mean PRA (P <
      0.05) level and PAI-1 activity (P < 0.05) were more pronounced in those with
      hypertensive parents than those without; conversely, the increase in NO levels
      was more pronounced in the latter group. No statistically or clinically
      significant difference was found between the mean body mass indices of these two
      groups. Only two subjects were overweight, and none were obese; the remainder had
      weights that were normal. We found no significant correlation between body mass
      index and either NO or PAI-1 level. CONCLUSION: Post-phlebotomy, PRA and PAI-1
      responses were more dramatic, but the NO response less in normotensive subjects
      having a parental history of hypertension, suggesting that these changes may
      represent familial, possibly genetic influences before overt hypertension occurs.

PMID- 19154323
TI  - Aldosterone induces collagen synthesis via activation of extracellular signal
      regulated kinase 1 and 2 in renal proximal tubules.
AB  - AIM: Aldosterone plays a crucial role in renal fibrosis by inducing mesangial
      cell proliferation and promoting collagen synthesis in renal fibroblasts.
      However, renal proximal tubule involvement in aldosterone-induced collagen
      synthesis has not yet been identified. The aim of this study was to examine the
      potential role of aldosterone in collagen expression and its possible
      mineralocorticoid receptor (MR)-dependent pathway, mediated by activation of
      extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured human renal
      proximal tubular epithelial (HKC) cells. METHODS: After HKC cells were stimulated
      by aldosterone with different concentrations for various time and periods, the
      gene expression and protein synthesis of collagen I, II, III and IV were measured
      by real-time polymerase chain reaction and western blot, respectively. ERK1/2
      activation, alpha-smooth muscle actin (alpha-SMA), and E-cadherin were also
      detected by western blot. RESULTS: Aldosterone can increase ERK1/2
      phosphorylation of human renal proximal tubular epithelial cells in a time- and
      dose-dependent manner. Although aldosterone had no effect on collagen I and II
      expression, it increased expression of alpha-SMA and collagen III and IV and
      decreased that of E-cadherin in HKC cells after 48 h. These effects could be
      prevented by a ERK pathway inhibitor, U0126, or by a selective MR antagonist,
      spironolactone. CONCLUSION: The results suggest that aldosterone plays a pivotal
      role in tubulointerstitial fibrosis by promoting tubular epithelial-mesenchymal
      transition and collagen synthesis in proximal tubular cells. The process is MR
      dependent, and mediated by ERK1/2 mitogen-activated protein kinase pathway.

PMID- 19154324
TI  - Review article: Use of renal registry data for research, health-care planning and
      quality improvement: what can we learn from registry data in the Asia-Pacific
      region?
AB  - We review renal registry data from the Asia-Pacific region with an emphasis on
      their uses in health care and in dialysis care in particular. The review aims to
      demonstrate the information value of registry data. While renal registry provides
      a useful data resource for epidemiological research, there are severe
      methodological limitations in its application for analytical or therapeutic
      research. However, it is the use of renal registry data for public health and
      health-care management purposes that registry really comes into its own, and it
      is primarily for these that governments have invested in national patient and
      disease registries. We apply data from several renal registries in the Asia
      Pacific region to illustrate its wide application for planning dialysis services,
      for evaluating dialysis practices and health outcomes, with a view to improving
      the quality of dialysis care. In the course of preparing the review, we have
      found that the quality and accessibility of renal registry data were highly
      variable across the region. Given the value of renal registry, every country in
      the Asia-Pacific region should establish one or should ensure that their current
      registries are better resourced and developed. Greater data sharing and
      collaboration among registries in the region could help advance the nephrology to
      serve our patients better.

PMID- 19154326
TI  - Human leucocyte antigen DQ alpha heterodimers and human leucocyte antigen DR
      alleles in tubulointerstitial nephritis and uveitis syndrome.

PMID- 19154327
TI  - Osmoregulation in Streptomyces coelicolor: modulation of SigB activity by OsaC.
AB  - As free-living non-motile saprophytes, Streptomyces need to adapt to a wide range
      of environmental conditions and this is reflected by an enormous diversity of
      regulatory proteins encoded by, for example, the genome of the model
      streptomycete Streptomyces coelicolor. In this organism, we have identified a new
      osmoregulation gene, osaC, encoding a member of a novel family of regulatory
      proteins. Members of the family have a predicted domain composition consisting of
      an N-terminal kinase domain related to anti-sigma factors, sensory Pas and Gaf
      domains, and a C-terminal phosphatase domain. osaC is linked to the response
      regulator gene osaB; expression analysis of the latter revealed that it is
      induced after osmotic stress in a sigma(B)-dependent manner. OsaC is required to
      return osaB and sigB expression back to constitutive levels after osmotic stress.
      From analysis of the activities of OsaC(DeltaPho), lacking the C-terminal
      phosphatase domain, and OsaC(N92A), with a substitution of a critical asparagine
      residue in the kinase domain, we infer that this N-terminal domain functions as a
      sigma(B) anti-sigma factor. Indeed, co-purification experiments indicate
      association of OsaC and sigma(B). These results support a model for post-osmotic
      stress modulation of sigma(B) activity by OsaC.

PMID- 19154328
TI  - Calcium homeostasis is required for contact-dependent helical and sinusoidal tip
      growth in Candida albicans hyphae.
AB  - Hyphae of the dimorphic fungus, Candida albicans, exhibit directional tip
      responses when grown in contact with surfaces. On hard surfaces or in liquid
      media, the trajectory of hyphal growth is typically linear, with tip re
      orientation events limited to encounters with topographical features
      (thigmotropism). In contrast, when grown on semisolid surfaces, the tips of C.
      albicans hyphae grow in an oscillatory manner to form regular two-dimensional
      sinusoidal curves and three-dimensional helices. We show that, like
      thigmotropism, initiation of directional tip oscillation in C. albicans hyphae is
      severely attenuated when Ca2+ homeostasis is perturbed. Chelation of
      extracellular Ca2+ or deletion of the Ca2+ transporters that modulate cytosolic
      [Ca2+] (Mid1, Cch1 or Pmr1) did not affect hyphal length but curve formation was
      severely reduced in mid1Delta and cch1Delta and abolished in pmr1Delta.
      Sinusoidal hypha morphology was altered in the mid1Delta, chs3Delta and
      heterozygous pmr1Delta/PMR1 strains. Treatments that affect cell wall integrity,
      changes in surface mannosylation or the provision of additional carbon sources
      had significant but less pronounced effects on oscillatory growth. The induction
      of two- and three-dimensional sinusoidal growth in wild-type C. albicans hyphae
      is therefore the consequence of mechanisms that involve Ca2+ influx and
      signalling rather than gross changes in the cell wall architecture.

PMID- 19154329
TI  - AgrD-dependent quorum sensing affects biofilm formation, invasion, virulence and
      global gene expression profiles in Listeria monocytogenes.
AB  - The Listeria monocytogenes Agr peptide-sensing system has been analysed by
      creating a deletion mutant in agrD, the structural gene for the putative quorum
      sensing peptide. The DeltaagrD mutant displayed significantly reduced biofilm
      formation, a defect which could be restored by genetic or physical
      complementation. A reduced invasion of Caco-2 intestinal epithelial cells was
      observed for the DeltaagrD mutant while phagocytosis by THP-1 macrophages was
      unaffected. Additionally, the level of internalin A (InlA) in the cell wall was
      decreased in the DeltaagrD mutant. Expression profiling of virulence genes (hlyA,
      actA, plcA, prfA and inlA) identified a finely tuned regulation which resulted in
      an impaired virulence response in the DeltaagrD mutant. The mutant is also
      significantly attenuated for virulence in mice, as revealed by bioluminescent in
      vivo imaging. On day 3 post infection, systemic dissemination to livers and
      spleens had occurred for the wild type, whereas the DeltaagrD mutant remained
      localized to the liver. Microarray analysis identified 126 and 670 genes as
      significantly regulated in exponential and stationary phase respectively. The
      results presented here suggest that peptide sensing plays an important role in
      the biology of L. monocytogenes, with relevant phenotypes in both the saprophytic
      and parasitic lifecycles.

PMID- 19154330
TI  - Control of translation initiation involves a factor-induced rearrangement of
      helix 44 of 16S ribosomal RNA.
AB  - Initiation of translation involves recognition of the start codon by the
      initiator tRNA in the 30S subunit. To investigate the role of ribosomal RNA
      (rRNA) in this process, we isolated a number of 16S rRNA mutations that increase
      translation from the non-canonical start codon AUC. These mutations cluster to
      distinct regions that overlap remarkably well with previously identified class
      III protection sites and implicate both IF1 and IF3 in start codon selection. Two
      mutations map to the 790 loop and presumably act by inhibiting IF3 binding.
      Another cluster of mutations surrounds the conserved A1413(o)G1487 base pair of
      helix 44 in a region known to be distorted by IF1 and IF3. Site-directed
      mutagenesis in this region confirmed that this factor-induced rearrangement of
      helix 44 helps regulate initiation fidelity. A third cluster of mutations maps to
      the neck of the 30S subunit, suggesting that the dynamics of the head domain
      influences translation initiation. In addition to identifying mutations that
      decrease fidelity, we found that many P-site mutations increase the stringency of
      start codon selection. These data provide evidence that the interaction between
      the initiator tRNA and the 30S P site is tuned to balance efficiency and accuracy
      during initiation.

PMID- 19154331
TI  - Single 23S rRNA mutations at the ribosomal peptidyl transferase centre confer
      resistance to valnemulin and other antibiotics in Mycobacterium smegmatis by
      perturbation of the drug binding pocket.
AB  - Tiamulin and valnemulin target the peptidyl transferase centre (PTC) on the
      bacterial ribosome. They are used in veterinary medicine to treat infections
      caused by a variety of bacterial pathogens, including the intestinal spirochetes
      Brachyspira spp. Mutations in ribosomal protein L3 and 23S rRNA have previously
      been associated with tiamulin resistance in Brachyspira spp. isolates, but as
      multiple mutations were isolated together, the roles of the individual mutations
      are unclear. In this work, individual 23S rRNA mutations associated with
      pleuromutilin resistance at positions 2055, 2447, 2504 and 2572 (Escherichia coli
      numbering) are introduced into a Mycobacterium smegmatis strain with a single
      rRNA operon. The single mutations each confer a significant and similar degree of
      valnemulin resistance and those at 2447 and 2504 also confer cross-resistance to
      other antibiotics that bind to the PTC in M. smegmatis. Antibiotic footprinting
      experiments on mutant ribosomes show that the introduced mutations cause
      structural perturbations at the PTC and reduced binding of pleuromutilin
      antibiotics. This work underscores the fact that mutations at nucleotides distant
      from the pleuromutilin binding site can confer the same level of valnemulin
      resistance as those at nucleotides abutting the bound drug, and suggests that the
      former function indirectly by altering local structure and flexibility at the
      drug binding pocket.

PMID- 19154332
TI  - Ribosomal protein L3 bound to 23S precursor rRNA stimulates its maturation by
      Mini-III ribonuclease.
AB  - Ribosomal RNAs (rRNAs) are processed from larger primary transcripts in every
      living system known. The maturation of 23S rRNA in Bacillus subtilis is catalysed
      by Mini-III, a member of the RNase III family of enzymes that lacks the
      characteristic double-stranded RNA binding domain of its relatives. We have
      previously shown that Mini-III processing of 23S precursor rRNA in assembled 50S
      ribosomal subunits is much more efficient than a substrate with no ribosomal
      proteins bound, suggesting that one or more large subunit proteins act as a
      cofactor for Mini-III cleavage. Here we show that this cofactor is ribosomal
      protein L3. Stimulation of the Mini-III cleavage reaction is through L3 binding
      to its normal site at the 3' end of 23S rRNA. We present indirect evidence that
      suggests that L3 acts at the level of substrate, rather than enzyme conformation.
      We also discuss the potential implication of using ribosomal protein cofactors in
      rRNA processing for ribosome quality control.

PMID- 19154333
TI  - Genome-wide regulon and crystal structure of BlaI (Rv1846c) from Mycobacterium
      tuberculosis.
AB  - Comparative genomics with Staphylococcus aureus suggested the existence of a
      regulatory system governing beta-lactamase (BlaC) production in Mycobacterium
      tuberculosis. The crystal structure of Rv1846c, a winged helix regulator of
      previously unknown function, was solved thus revealing strong similarity to the
      BlaI and MecI repressors of S. aureus, which both respond to beta-lactam
      treatment. Using chromatin immunoprecipitation and hybridization to microarrays
      (ChIP-on-chip), the Rv1846c regulon was shown to comprise five separate genomic
      loci. Two of these mediate responses and resistance to beta-lactam antibiotics
      (rv1845c, rv1846c-rv1847; blaC-sigC); two encode membrane proteins of unknown
      function (rv1456c, rv3921c) while the last codes for ATP synthase (rv1303
      atpBEFHAGDC-rv1312). The ChIP-on-chip findings were confirmed independently using
      electrophoretic mobility shift assays, DNAse footprinting and transcript analysis
      leading to Rv1846c being renamed BlaI. When cells were treated with beta-lactams,
      BlaI was released from its operator sites causing derepression of the regulon and
      upregulation of ATP synthase transcription. The existence of a potential
      regulatory loop between cell wall integrity and ATP production was previously
      unknown.

PMID- 19154334
TI  - An emerging view of presynaptic structure from electron microscopic studies.
AB  - In response to calcium influx, some of the synaptic vesicles in presynaptic
      terminals fuse rapidly with the presynaptic membrane, allowing fast synaptic
      transmission. The regulated recycling of synaptic vesicles at the terminals is
      required for a sustained release of neurotransmitters. Localization of 'ready to
      be released' vesicles in close vicinities to voltage-gated calcium channels
      enables the rapid release of neurotransmitters. Thus, recycling vesicles must
      translocate from the sites of endocytosis to these release sites. However, the
      sub-cellular organization that supports this local vesicular traffic remains
      poorly understood. We will review the results of various electron microscopy
      studies, which have begun to unveil the structure of presynaptic terminals.

PMID- 19154335
TI  - A reappraisal of the central effects of botulinum neurotoxin type A: by what
      mechanism?
AB  - Botulinum neurotoxin A (BoNT/A) is a metalloprotease that enters peripheral motor
      nerve terminals and blocks the release of acetylcholine via the specific cleavage
      of the synaptosomal-associated protein of 25-kDa. Localized injections of BoNT/A
      are widely employed in clinical neurology to treat several human diseases
      characterized by muscle hyperactivity. It is generally assumed that the effects
      of BoNT/A remain localized to the injection site. However, several
      neurophysiological studies have provided evidence for central effects of BoNT/A,
      raising the issue of how these actions arise. Here we review these data and
      discuss the possibility that retrograde axonal transport of catalytically active
      BoNT/A may explain at least some of its effects at the level of central circuits.

PMID- 19154337
TI  - RNA editing of the serotonin 2C receptor and expression of Galpha(q) protein:
      genetic mouse models do not support a role for regulation or compensation.
AB  - The serotonin 2C (5-HT(2C)) receptor undergoes RNA editing at five bases in a
      region of the pre-mRNA encoding the second intracellular loop, generating many
      unique 5-HT(2C) receptor isoforms. Mechanisms regulating in vivo expression of
      different edited 5-HT(2C) receptor isoforms are poorly understood, as are the
      adaptive consequences of variation in editing profiles. Recent findings suggest a
      putative relationship between expression levels of Galpha(q/11) protein and the
      degree of editing of 5-HT(2C) receptor transcripts. To elucidate the potential
      regulatory or adaptive role of Galpha(q/11) protein levels, we quantified editing
      of 5-HT(2C) receptor RNA transcripts in Galpha(q) null mice and protein levels of
      Galpha(q) and Galpha(11) in transgenic male mice solely expressing either the non
      edited (INI) or the fully edited (VGV) isoforms of the 5-HT(2C) receptor.
      Pyrosequencing of RNA isolated from amygdaloid cortex in Galpha(q) null and wild
      type mice revealed no significant differences in 5-HT(2C) receptor mRNA editing
      profiles. Cortical tissue from INI/y, VGV/y, and wild-type mice was assayed for
      expression of Galpha(q) and Galpha(11) subunits by Western blotting. No
      differences in signal density between wild-type and INI/y or VGV/y groups were
      found, indicating equivalent levels of Galpha(q) and Galpha(11) protein.
      Together, these data do not support a causal or compensatory relationship between
      5-HT(2C) receptor RNA editing and G(q) protein levels.

PMID- 19154338
TI  - Multiple protective activities of neuroglobin in cultured neuronal cells exposed
      to hypoxia re-oxygenation injury.
AB  - Oxidative stress is associated with the pathology of acute and chronic
      neurodegenerative disease. We have cloned a human neuroglobin (Nb) construct and
      over-expressed this protein in cultured human neuronal cells to assess whether Nb
      ameliorates the cellular response to experimental hypoxia-reoxygenation (H/R)
      injury. Parental cells transfected with a blank (pDEST40) vector responded to H/R
      injury with a significant decrease in cellular ATP at 5 and 24 h after insult.
      This was coupled with increases in the cytosolic Ca(2+), and the transition
      metals iron (Fe), copper (Cu), and zinc (Zn) within the cell body, as monitored
      simultaneously using X-ray fluorescence microprobe imaging. Parental cell
      viability decreased over the same time period with a approximately 4 to 5-fold
      increase in cell death (maximum approximately 25%) matched by an increase in
      caspase 3/7 activation (peaking at a 15-fold increase after 24 h) and
      condensation of beta-actin along axonal processes. Over-expression of Nb
      inhibited ATP loss and except for significant decreases in the sulfur (S),
      chlorine (Cl), potassium (K) and Ca(2+) contents, maintained cellular ion
      homeostasis after H/R insult. This resulted in increased cell viability,
      significantly diminished caspase activation and maintenance of the beta-actin
      cytoskeletal structure and receptor-mediated endocytosis. These data indicate
      that bolstering the cellular content of Nb inhibits neuronal cell dysfunction
      promoted by H/R insult through multiple protective actions including: (i)
      maintenance of cellular bioenergetics; (ii) inhibition of Ca(2+) influx; (iii) a
      reduction in cellular uptake of Fe, Cu and Zn at the expense of S, Cl and K; and
      (iv) an enhancement of cell viability through inhibiting necrosis and apoptosis.

PMID- 19154341
TI  - Frataxin deficiency causes upregulation of mitochondrial Lon and ClpP proteases
      and severe loss of mitochondrial Fe-S proteins.
AB  - Friedreich ataxia (FRDA) is a rare hereditary neurodegenerative disease
      characterized by progressive ataxia and cardiomyopathy. The cause of the disease
      is a defect in mitochondrial frataxin, an iron chaperone involved in the
      maturation of Fe-S cluster proteins. Several human diseases, including
      cardiomyopathies, have been found to result from deficiencies in the activity of
      specific proteases, which have important roles in protein turnover and in the
      removal of damaged or unneeded protein. In this study, using the muscle creatine
      kinase mouse heart model for FRDA, we show a clear progressive increase in
      protein levels of two important mitochondrial ATP-dependent proteases, Lon and
      ClpP, in the hearts of muscle creatine kinase mutants. These proteases have been
      shown to degrade unfolded and damaged proteins in the matrix of mitochondria.
      Their upregulation, which was triggered at a mid-stage of the disease through
      separate pathways, was accompanied by an increase in proteolytic activity. We
      also demonstrate a simultaneous and significant progressive loss of mitochondrial
      Fe-S proteins with no substantial change in their mRNA level. The correlative
      effect of Lon and ClpP upregulation on loss of mitochondrial Fe-S proteins during
      the progression of the disease may suggest that Fe-S proteins are potential
      targets of Lon and ClpP proteases in FRDA.

PMID- 19154336
TI  - Inflammation mediates varying effects in neurogenesis: relevance to the
      pathogenesis of brain injury and neurodegenerative disorders.
AB  - Brain inflammation is a complex cellular and molecular response to stress, injury
      or infection of the CNS in attempt to defend against insults, clear dead and
      damaged neurons and return the CNS to a normal state. Inflammation in the CNS is
      driven by the activation of resident microglia, astrocytes and infiltrating
      peripheral macrophages, which release a plethora of anti- and pro-inflammatory
      cytokines, chemokines, neurotransmitters and reactive oxygen species. This
      inflammatory state inadvertently causes further bystander damage to neurons and
      produces both detrimental and favorable conditions for neurogenesis. Inflammatory
      factors have varying effects on neural progenitor cell proliferation, migration,
      differentiation, survival and incorporation of newly born neurons into the CNS
      circuitry. The unique profile of inflammatory factors, which depends on the
      severity of inflammation, can have varying consequences on neurogenesis.
      Inflammatory factors released during mild acute inflammation usually stimulate
      neurogenesis; where as the factors released by uncontrolled inflammation create
      an environment that is detrimental to neurogenesis. This review will provide a
      summary of current progress in this emerging field and examine the potential
      mechanisms through which inflammation affects neurogenesis during neurological
      complications.

PMID- 19154342
TI  - The multi-replication protein A (RPA) system--a new perspective.
AB  - Replication protein A (RPA) complex has been shown, using both in vivo and in
      vitro approaches, to be required for most aspects of eukaryotic DNA metabolism:
      replication, repair, telomere maintenance and homologous recombination. Here, we
      review recent data concerning the function and biological importance of the multi
      RPA complex. There are distinct complexes of RPA found in the biological
      kingdoms, although for a long time only one type of RPA complex was believed to
      be present in eukaryotes. Each complex probably serves a different role. In
      higher plants, three distinct large and medium subunits are present, but only one
      species of the smallest subunit. Each of these protein subunits forms stable
      complexes with their respective partners. They are paralogs as complex. Humans
      possess two paralogs and one analog of RPA. The multi-RPA system can be regarded
      as universal in eukaryotes. Among eukaryotic kingdoms, paralogs, orthologs,
      analogs and heterologs of many DNA synthesis-related factors, including RPA, are
      ubiquitous. Convergent evolution seems to be ubiquitous in these processes. Using
      recent findings, we review the composition and biological functions of RPA
      complexes.

PMID- 19154343
TI  - Identification of novel carbohydrate modifications on Campylobacter jejuni 11168
      flagellin using metabolomics-based approaches.
AB  - It is well known that the flagellin of Campylobacter jejuni is extensively
      glycosylated by pseudaminic acid and the related acetamindino derivative, in
      addition to flagellin glycosylation being essential for motility and colonization
      of host cells. Recently, the use of metabolomics permitted the unequivocal
      characterization of unique flagellin modifications in Campylobacter, including
      novel legionaminic acid sugars in Campylobacter coli, which had been impossible
      to ascertain in earlier studies using proteomics-based approaches. To date, the
      precise identities of the flagellin glycosylation modifications have only been
      elucidated for C. jejuni 81-176 and C. coli VC167 and those present in the first
      genome-sequenced strain C. jejuni 11168 remain elusive due to lability and
      respective levels of individual glycan modifications. We report the
      characterization of the carbohydrate modifications on C. jejuni 11168 flagellin
      using metabolomics-based approaches. Detected as their corresponding CMP-linked
      precursors, structural information on the flagellin modifications was obtained
      using a combination of MS and NMR spectroscopy. In addition to the pseudaminic
      acid and legionaminic acid sugars known to be present on Campylobacter flagellin,
      two unusual 2,3-di-O-methylglyceric acid modifications of a nonulosonate sugar
      were identified. By performing a metabolomic analysis of selected isogenic
      mutants of genes from the flagellin glycosylation locus of this pathogen, these
      novel CMP-linked precursors were confirmed to be di-O-methylglyceric acid
      derivatives of pseudaminic acid and the related acetamidino sugar. This is the
      first comprehensive analysis of the flagellar modifications in C. jejuni 11168
      and structural elucidation of di-O-methylglyceric acid derivatives of pseudaminic
      acid on Campylobacter flagellin.

PMID- 19154344
TI  - A systems biological approach suggests that transcriptional feedback regulation
      by dual-specificity phosphatase 6 shapes extracellular signal-related kinase
      activity in RAS-transformed fibroblasts.
AB  - Mitogen-activated protein kinase (MAPK) signaling determines crucial cell fate
      decisions in most cell types, and mediates cellular transformation in many types
      of cancer. The activity of MAPK is controlled by reversible phosphorylation, and
      the quantitative characteristics of MAPK activation determine the cellular
      response. Many systems biological studies have analyzed the activation kinetics
      and the dose-response behavior of the MAPK signaling pathway. Here we investigate
      how the pathway activity is controlled by transcriptional feedback loops.
      Initially, we predict that MAPK signaling regulates phosphatases, by integrating
      promoter sequence data and ontology-based classification of gene function. From
      this, we deduce that MAPK signaling might be controlled by transcriptional
      negative feedback regulation via dual-specificity phosphatases (DUSPs), and
      implement a mathematical model to further test this hypothesis. Using time
      resolved measurements of pathway activity and gene expression, we employ a model
      selection approach, and select DUSP6 as a highly likely candidate for shaping the
      activity of the MAPK pathway during cellular transformation caused by oncogenic
      RAS. Two predictions from the model were confirmed: first, feedback regulation
      requires that DUSP6 mRNA and protein are unstable; and second, the activation
      kinetics of MAPK are ultrasensitive. Taken together, an integrated systems
      biological approach reveals that transcriptional negative feedback controls the
      kinetics and the extent of MAPK activation under both physiological and
      pathological conditions.

PMID- 19154345
TI  - cGMP-dependent protein kinase II and aldosterone secretion.
AB  - ACTH-stimulated aldosterone secretion can be inhibited by atrio-natriuretic
      peptide/cGMP. The mechanism behind this modulation has been reported to involve
      cGMP-dependent activation of phosphodiesterase 2 (PDE2) and hydrolysis of cAMP.
      Recently it was reported that activation of cGMP-dependent protein kinase II
      (cGKII) stimulated aldosterone secretion in rat zona glomerulosa cells. The zona
      glomerulosa of the murine adrenal cortex expresses cGKII and PDE2. We used mice
      with a homozygous inactivation of the cGKII gene to investigate in vivo the
      potential role of this kinase in aldosterone secretion. Basal plasma renin and
      aldosterone levels were similar in wild-type and cGKII(-/-) mice. In vivo
      injection of atrio-natriuretic peptide decreased ACTH-stimulated aldosterone
      secretion in wild-type mice, but had no effect in cGKII-deficient mice. These
      results support the view that cGKII modulates aldosterone secretion in the murine
      adrenal cortex.

PMID- 19154346
TI  - Structural framework of the GABARAP-calreticulin interface--implications for
      substrate binding to endoplasmic reticulum chaperones.
AB  - The 4-aminobutyrate type A receptor-associated protein (GABARAP) is a versatile
      adaptor protein that plays an important role in intracellular vesicle
      trafficking, particularly in neuronal cells. We have investigated the structural
      determinants underlying the interaction of GABARAP with calreticulin using
      spectroscopic and crystallographic techniques. Specifically, we present the
      crystal structure of GABARAP in complex with its major binding epitope on the
      chaperone. Molecular modeling of a complex containing full-length calreticulin
      suggests a novel mode of substrate interaction, which may have functional
      implications for the calreticulin/calnexin family in general.

PMID- 19154347
TI  - Transcription factor specificity protein 1 (SP1) and activating protein 2alpha
      (AP-2alpha) regulate expression of human KCTD10 gene by binding to proximal
      region of promoter.
AB  - Potassium channel tetramerization domain-containing 10 gene (KCTD10) belongs to
      the polymerase delta-interacting protein 1 (PDIP1) gene family. Mouse KCTD10 was
      thought to interact with proliferating cell nuclear antigen and the small subunit
      of polymerase delta, and to have roles in DNA repair, DNA replication and cell
      cycle control. To better understand the regulatory mechanism of KCTD10
      expression, we characterized the promoter of human KCTD10 containing a 639 bp
      fragment of the 5'-flanking region (-609/+30). A primer extension assay
      identified the transcription start site as an A, 63 bp upstream of the start
      codon. The promoter region contains neither a TATA box nor a CCAAT box, but a CpG
      island was found near to the transcription start site. Deletion mutagenesis
      showed that the region from -108 to +30 was indispensable to the promoter
      activity, and site-directed mutation analysis in this proximal promoter region of
      KCTD10 revealed two important transcription regulatory elements of specificity
      protein 1 (SP1) and activating protein-2 (AP-2). An in vivo chromatin
      immunoprecipitation assay further demonstrated that SP1 and AP-2alpha could bind
      to this proximal promoter region. Moreover, using a luciferase reporter assay,
      quantitative real-time RT-PCR and western blot analysis, both overexpression and
      RNA interference of SP1 and AP-2alpha indicated that the binding of SP1 to the
      proximal promoter region stimulated the promoter activity and endogenous KCTD10
      expression, whereas binding of AP-2alpha to this region showed opposite effects.

PMID- 19154348
TI  - Unchanged thymidine triphosphate pools and thymidine metabolism in two lines of
      thymidine kinase 2-mutated fibroblasts.
AB  - Mitochondrial thymidine kinase (TK2) catalyzes the phosphorylation of thymidine
      in mitochondria. Its function becomes essential for dTTP synthesis in noncycling
      cells, where cytosolic dTTP synthesis via R1/R2 ribonucleotide reductase and
      thymidine kinase 1 is turned down. Mutations in the nuclear gene for TK2 cause a
      fatal mtDNA depletion syndrome. Only selected cell types are affected, suggesting
      that the other cells compensate for the TK2 deficiency by adapting the enzyme
      network that regulates dTTP synthesis outside S-phase. Here we looked for such
      metabolic adaptation in quiescent cultures of fibroblasts from two TK2-deficient
      patients with a slow-progressing syndrome. In cell extracts, we measured the
      activities of TK2, deoxycytidine kinase, thymidine phosphorylase,
      deoxynucleotidases and the amounts of the three ribonucleotide reductase
      subunits. Patient cells contained 40% or 5% TK2 activity and unchanged activities
      of the other enzymes. However, their mitochondrial and cytosolic dTTP pools were
      unchanged, and also the overall composition of the dNTP pools was normal. TK2
      dependent phosphorylation of [(3)H]thymidine in intact cells and the turnover of
      the dTTP pool showed that even the fibroblasts with 5% residual TK2 activity
      synthesized dTTP at an almost normal rate. Normal fibroblasts apparently contain
      more TK2 than needed to maintain dTTP during quiescence, which would explain why
      TK2-mutated fibroblasts do not manifest mtDNA depletion despite their reduced TK2
      activity.

PMID- 19154349
TI  - Polyphosphates from Mycobacterium bovis--potent inhibitors of class III adenylate
      cyclases.
AB  - cAMP generation in bacteria is often stimulated by sudden, but lasting, changes
      in extracellular conditions, whereas intracellular cAMP concentrations quickly
      settle at new levels. As bacteria lack G-proteins, it is unknown how bacterial
      adenylate cyclase (AC) activities are modulated. Mycobacterium tuberculosis has
      15 class III AC genes; therefore, we examined whether mycobacteria contain a
      factor that may regulate AC activities. We identified mycobacterial
      polyphosphates with a mean chain length of 72 residues as highly potent
      inhibitors of dimeric class IIIa, class IIIb and class IIIc ACs from M.
      tuberculosis and other bacteria. The identity of the inhibitor was established by
      phosphatase degradation, 31P-NMR, acid or base hydrolysis, PAGE and comparisons
      with commercial standards, and functional substitution by several polyphosphates.
      The data indicate that each AC dimer occupies 8-15 phosphate residues on a
      polyphosphate strand. Other polyionic polymers such as polyglutamate, polylysine
      and hyaluronic acid do not affect cyclase activity. Notably, the structurally
      unrelated class I AC Cya from Escherichia coli is unaffected. Bacterial
      polyphosphate metabolism is generally viewed in the context of stress-related
      regulatory networks. Thus, regulation of bacterial class III ACs by
      polyphosphates could be a component of the bacterial stress response.

PMID- 19154350
TI  - What determines the degree of compactness of a calcium-binding protein?
AB  - The EF-hand calcium-binding proteins may exist either in an extended or a compact
      conformation. This conformation is sometimes correlated with the function of the
      calcium-binding protein. For those proteins whose structure and function are
      known, calcium sensors are usually extended and calcium buffers compact; hence,
      there is interest in predicting the form of the protein starting from its
      sequence. In the present study, we used two different procedures: one that
      already exists in the literature, the sosuidumbbell algorithm, mainly based on
      the charges of the two EF-hand domains, and the other comprising a novel
      procedure that is based on linker average hydrophilicity. The linker consists of
      the residues that connect the domains. The two procedures were tested on 17 known
      structure calcium-binding proteins and then applied to 59 unknown-structure
      centrins. The sosuidumbbell algorithm yielded the correct conformations for only
      15 of the known-structure proteins and predicted that all centrins should be in a
      closed form. The linker average hydrophilicity procedure discriminated well
      between all the extended and non-extended forms of the known-structure calcium
      binding proteins, and its prediction concerning centrins reflected well their
      phylogenetic classification. The linker average hydrophilicity criterion is a
      simple and powerful means to discriminate between extended and non-extended forms
      of calcium-binding proteins. What is remarkable is that only a few residues that
      constitute the linker (between 2 and 20 in our tested sample of proteins) are
      responsible for the form of the calcium-binding protein, showing that this form
      is mainly governed by short-range interactions.

PMID- 19154351
TI  - Identification of the N-termini of NADPH : protochlorophyllide oxidoreductase A
      and B from barley etioplasts (Hordeum vulgare L.).
AB  - The N-termini of the NADPH : protochlorophyllide oxidoreductase (POR) proteins A
      and B from barley and POR from pea were determined by acetylation of the proteins
      and selective isolation of the N-terminal peptides for mass spectrometry de novo
      sequence analysis. We show that the cleavage sites between the transit peptides
      and the three mature POR proteins are homologous. The N-terminus in PORA is V48,
      that in PORB is A61, and that in POR from pea is E64. For the PORB protein, two
      additional N-termini were identified as A62 and A63, with decreased signal
      intensity of the corresponding N-terminal peptides. The results show that the
      transit peptide of PORA is considerably shorter than previously reported and
      predicted by ChloroP. A pentapeptide motif that has been characterized as
      responsible for binding of protochlorophyllide to the transit peptide of PORA
      [Reinbothe C, Pollmann S, Phetsarath-Faure P, Quigley F, Weisbeek P & Reinbothe S
      (2008) Plant Physiol148, 694-703] is shown here to be part of the mature PORA
      protein.

PMID- 19154352
TI  - Murine serum nucleases--contrasting effects of plasmin and heparin on the
      activities of DNase1 and DNase1-like 3 (DNase1l3).
AB  - DNase1 is regarded as the major serum nuclease; however, a systematic
      investigation into the presence of additional serum nuclease activities is
      lacking. We have demonstrated directly that serum contains DNase1-like 3
      (DNase1l3) in addition to DNase1 by an improved denaturing SDS-PAGE zymography
      method and anti-murine DNase1l3 immunoblotting. Using DNA degradation assays, we
      compared the activities of recombinant murine DNase1 and DNase1l3 (rmDNase1,
      rmDNase1l3) with the serum of wild-type and DNase1 knockout mice. Serum and
      rmDNase1 degrade chromatin effectively only in cooperation with serine proteases,
      such as plasmin or thrombin, which remove DNA-bound proteins. This can be
      mimicked by the addition of heparin, which displaces histones from chromatin. In
      contrast, serum and rmDNase1l3 degrade chromatin without proteolytic help and are
      directly inhibited by heparin and proteolysis by plasmin. In previous studies,
      serum DNase1l3 escaped detection because of its sensitivity to proteolysis by
      plasmin after activation of the plasminogen system in the DNA degradation assays.
      In contrast, DNase1 is resistant to plasmin, probably as a result of its di-N
      glycosylation, which is lacking in DNase1l3. Our data demonstrate that secreted
      rmDNase1 and murine parotid DNase1 are mixtures of three different di-N
      glycosylated molecules containing two high-mannose, two complex N-glycans or one
      high-mannose and one complex N-glycan moiety. In summary, serum contains two
      nucleases, DNase1 and DNase1l3, which may substitute or cooperate with each other
      during DNA degradation, providing effective clearance after exposure or release
      from dying cells.

PMID- 19154354
TI  - Testing the quality of a carrier: a field experiment on lizard signalers.
AB  - In the Australian painted dragon lizard (Ctenophorus pictus), males occur in two
      different morphs with respect to gular color, with or without a yellow bib. Males
      without a bib lost within-clutch paternity significantly more often to rivals
      than bibbed males. Thus, it appears that bibs identify some phenotypic advantage
      linked to competitive ability. To test whether this could be related to whole
      organism capacity to withstand an increased workload (due to better health and
      vigor, or evolved differences in self-maintenance), we implanted males with a
      lead pellet (loaded), Styrofoam pellet (controls), or sham-operated males without
      implants (shams), and compared male categories with respect to how they
      maintained body mass during the mating season. Somewhat unexpectedly, bibbed
      males consistently lost more body weight across all treatments and controls,
      although we could not verify that this translated into higher mortality in this
      short-lived animal (about 80% survive for one year only). However, bibbed males
      may invest more into "mating success" than nonbibbed males, which agrees with our
      experimental results and paternity data.

PMID- 19154353
TI  - Crystal structure of a family 16 endoglucanase from the hyperthermophile
      Pyrococcus furiosus--structural basis of substrate recognition.
AB  - Bacterial and archaeal endo-beta-1,3-glucanases that belong to glycoside
      hydrolase family 16 share a beta-jelly-roll fold, but differ significantly in
      sequence and in substrate specificity. The crystal structure of the laminarinase
      (EC 3.2.1.39) from the hyperthermophilic archaeon Pyrococcus furiosus (pfLamA)
      has been determined at 2.1 A resolution by molecular replacement. The pfLamA
      structure reveals a kink of six residues (72-77) at the entrance of the catalytic
      cleft. This peptide is absent in the endoglucanases from alkaliphilic
      Nocardiopsis sp. strain F96 and Bacillus macerans, two proteins displaying an
      overall fold similar to that of pfLamA, but with different substrate specificity.
      A deletion mutant of pfLamA, lacking residues 72-75, hydrolyses the mixed-linkage
      beta-1,3-1,4-glucan lichenan 10 times more efficiently than the wild-type
      protein, indicating the importance of the kink in substrate preference.

PMID- 19154355
TI  - Evolution in a constant environment: thermal fluctuations and thermal sensitivity
      of laboratory and field populations of Manduca sexta.
AB  - Adaptation to temporal variation in environmental conditions is widespread.
      Whether evolution in a constant environment alters adaptation to temporal
      variation is relatively unexplored. We examine how constant and diurnally
      fluctuating temperature conditions affect life-history traits in two populations
      of the tobacco hornworm, Manduca sexta: a field population that routinely
      experiences fluctuating temperatures; and a laboratory population (derived from
      this field population in the 1960s) maintained at a constant temperature for more
      than 250 generations. Our experiments demonstrate that diurnal fluctuations
      significantly alter body size and development time in both populations, and
      confirm that these populations differ in their responses to a mean temperature.
      However, we found no evidence for population divergence in responses to diurnal
      temperature fluctuations. We suggest that mean and extreme temperatures may act
      as more potent selective forces on thermal reaction norms than temperature
      variation per se.

PMID- 19154356
TI  - Range disjunctions, speciation, and morphological transformation rates in the
      liverwort genus Leptoscyphus.
AB  - Bryophytes and angiosperms exhibit similar intercontinental disjunct
      distributions that have traditionally been explained by continental drift. Such
      disjunct distributions are, however, typically observed at the species level in
      bryophytes, whereas they occur at much higher taxonomic level in angiosperms. The
      corollary of this observation is that morphological evolution in bryophytes is
      exceedingly slow. These hypotheses can now be explicitly tested with the advent
      of molecular dating. In this article, we show that the trans-Atlantic
      disjunctions observed in the mostly tropical liverwort genus Leptoscyphus date
      back to 5.5 Myr, thus largely postdating the opening of the South Atlantic. The
      temporal calibration of the phylogeny allows us to estimate for the first time
      the absolute timing of morphological evolution in bryophytes. The time frame
      necessary for shifts to occur between character states was estimated on average
      at ca. 4.05+/-1.86 Myr. As opposed to the traditional view that bryophyte
      evolution has been triggered by episodic shifts in habitat conditions, our
      analyses furthermore suggest that morphological and molecular divergence
      gradually accumulated in the genus, which contrasts with the rapid
      diversification documented in some tropical trees.

PMID- 19154357
TI  - A multilocus test of simultaneous divergence across the Isthmus of Panama using
      snapping shrimp in the genus Alpheus.
AB  - The completion of the Panamanian Isthmus is one of the greatest natural
      experiments in evolution, sending multiple species pairs from a broad range of
      taxonomic groups on independent evolutionary trajectories. The resulting
      transisthmian sister species have been used as model systems for examining
      consequences that accompany cessation of gene flow in formerly panmictic
      populations. However, variance in pairwise genetic distances of these "geminates"
      often exceeds expectations, seemingly conflicting with the assumption that
      separation of populations was contemporaneous with the final closure of the
      Isthmus. Multilocus datasets and coalescent-based analytical methods can be used
      to estimate divergence times while accounting for variance in gene divergence
      that predates isolation, thus removing the need to invoke unequal divergence
      times. Here we present results from Bayesian analyses of sequence data from seven
      nuclear and one mitochondrial marker in eight transisthmian species pairs in the
      snapping shrimp genus Alpheus. Divergence times in two species pairs were shown
      to occur much earlier than the Isthmus final closure, but much of the variance in
      pairwise genetic distances from cytochrome oxidase I (COI) was explained when
      ancestral polymorphisms were accounted for. Results illustrate how coalescent
      approaches may be more appropriate for dating recent divergences than for
      estimating ancient speciation events.

PMID- 19154358
TI  - When should a trophically transmitted parasite manipulate its host?
AB  - We investigate evolution of two categories of adaptive host manipulation by
      trophically transmitted helminths: (1) predation suppression decreases the host's
      mortality before the helminth is capable of establishing in its next host; (2)
      predation enhancement increases the existing host's mortality after it can
      establish in its next host. If all parasite mortality is purely random (time
      independent), enhancement must increase predation by the next host sufficiently
      more (depending on manipulative costs) than it increases the average for all
      forms of host mortality; thus if host and parasite die only through random
      predation, manipulation must increase the "right" predation more than the "wrong"
      predation. But if almost all parasites die in their intermediate host through
      reaching the end of a fixed life span, enhancement can evolve if it increases the
      right predation, regardless of how much it attracts wrong predators. Although
      enhancement is always most favorable when it targets the right host, suppression
      aids survival to the time when establishment in the next host is possible: it is
      most favorable if it reduces all aspects of host (and hence parasite) mortality.
      If constrained to have selective effects, suppression should reduce the commonest
      form of mortality.

PMID- 19154359
TI  - Sex differences in mate recognition and conspecific preference in species with
      mutual mate choice.
AB  - Sexual isolation is often assumed to arise because choosy females recognize and
      reject heterospecific males as mates. Yet in taxa in which both males and females
      are choosy, males might also recognize and reject heterospecific females. Here,
      we asked about the relative contribution of the sexes to the strong sexual
      isolation found in limnetic-benthic species pairs of threespine sticklebacks,
      which show mutual mate choice. We asked whether males and females of the two
      species recognize conspecifics and also prefer to mate with them. We found
      evidence for mate recognition by both sexes but only females prefer conspecifics.
      The nature of male courtship depended on which species of female they were
      courting, indicating that males recognized conspecific females and differentiated
      them from heterospecifics. However, males courted both species of females with
      equal vigor and changed courtship in a manner that would increase the chance of
      mating with heterospecifics. Females both recognized conspecifics and strongly
      preferred them. They responded very little to heterospecific male courtship and
      almost never mated with them. Therefore, males are likely to undermine sexual
      isolation, but females uphold it. Despite mutual mate choice and mate recognition
      in both sexes, females are primarily responsible for sexual isolation in these
      taxa.

PMID- 19154360
TI  - Patterns of threshold evolution in polyphenic insects under different
      developmental models.
AB  - Two hypotheses address the evolution of polyphenic traits in insects. Under the
      developmental reprogramming model, individuals exceeding a threshold follow a
      different developmental pathway from individuals below the threshold. This
      decoupling is thought to free selection to independently hone alternative
      morphologies, increasing phenotypic plasticity and morphological diversity. Under
      the alternative model, extreme positive allometry explains the existence of
      alternative phenotypes and divergent phenotypes are developmentally coupled by a
      continuous reaction norm, such that selection on either morph acts on both. We
      test the hypothesis that continuous reaction norm polyphenisms, evolve through
      changes in the allometric parameters of even the smallest males with minimal
      trait expression, whereas threshold polyphenisms evolve independent of the
      allometric parameters of individuals below the threshold. We compare two
      polyphenic species; the dung beetle Onthophagus taurus, whose allometry has been
      modeled both as a threshold polyphenism and a continuous reaction norm and the
      earwig Forficula auricularia, whose allometry is best modeled with a
      discontinuous threshold. We find that across populations of both species,
      variation in forceps or horn allometry in minor males are correlated to the
      population's threshold. These findings suggest that regardless of developmental
      mode, alternative morphs do not evolve independently of one another.

PMID- 19154361
TI  - Evolution of leaf form in marsileaceous ferns: evidence for heterochrony.
AB  - Using an explicit phylogenetic framework, ontogenetic patterns of leaf form are
      compared among the three genera of marsileaceous ferns (Marsilea, Regnellidium,
      and Pilularia) with the outgroup Asplenium to address the hypothesis that
      heterochrony played a role in their evolution. We performed a Fourier analysis on
      a developmental sequence of leaves from individuals of these genera. Principal
      components analysis of the harmonic coefficients was used to characterize the
      ontogenetic trajectories of leaf form in a smaller dimensional space. Results of
      this study suggest that the "evolutionary juvenilization" observed in these leaf
      sequences is best described using a mixed model of heterochrony (accelerated
      growth rate and early termination at a simplified leaf form). The later stages of
      the ancestral, more complex, ontogenetic pattern were lost in Marsileaceae,
      giving rise to the simplified adult leaves of Marsilea, Regnellidium, and
      Pilularia. Life-history traits such as ephemeral and uncertain habitats, high
      reproductive rates, and accelerated maturation, which are typical for
      marsileaceous ferns, suggest that they may be "r strategists." The evidence for
      heterochrony presented here illustrates that it has resulted in profound
      ecological and morphological consequences for the entire life history of
      Marsileaceae.

PMID- 19154362
TI  - Thermoregulation constrains effective warning signal expression.
AB  - Evolution of conspicuous signals may be constrained if animal coloration has
      nonsignaling as well as signaling functions. In aposematic wood tiger moth
      (Parasemia plantaginis) larvae, the size of a warning signal (orange patch on
      black body) varies phenotypically and genetically. Although a large warning
      signal is favored as an antipredator defense, we hypothesized that
      thermoregulation may constrain the signal size in colder habitats. To test this
      hypothesis, we conducted a factorial rearing experiment with two selection lines
      for larval coloration (small and large signal) and with two temperature
      manipulations (high and low temperature environment). Temperature constrained the
      size and brightness of the warning signal. Larvae with a small signal had an
      advantage in the colder environment, which was demonstrated by a faster
      development time and growth rate in the low temperature treatment, compared to
      larvae with a large signal. Interestingly, the larvae with a small signal were
      found more often on the plant than the ones with a large signal, suggesting
      higher basking activity of the melanic (small signal) individuals in the low
      temperature. We conclude that the expression of aposematic display is not only
      defined by its efficacy against predators; variation in temperature may constrain
      evolution of a conspicuous warning signal and maintain variation in it.

PMID- 19154363
TI  - Ecological conditions affect evolutionary trajectory in a predator-prey system.
AB  - The arms race of adaptation and counter adaptation in predator-prey interactions
      is a fascinating evolutionary dynamic with many consequences, including local
      adaptation and the promotion or maintenance of diversity. Although such
      antagonistic coevolution is suspected to be widespread in nature, experimental
      documentation of the process remains scant, and we have little understanding of
      the impact of ecological conditions. Here, we present evidence of predator-prey
      coevolution in a long-term experiment involving the predatory bacterium
      Bdellovibrio bacteriovorus and the prey Pseudomonas fluorescens, which has three
      morphs (SM, FS, and WS). Depending on experimentally applied disturbance regimes,
      the predator-prey system followed two distinct evolutionary trajectories, where
      the prey evolved to be either super-resistant to predation (SM morph) without
      counter-adaptation by the predator, or moderately resistant (FS morph),
      specialized to and coevolving with the predator. Although predation-resistant FS
      morphs suffer a cost of resistance, the evolution of extreme resistance to
      predation by the SM morph was apparently unconstrained by other traits (carrying
      capacity, growth rate). Thus we demonstrate empirically that ecological
      conditions can shape the evolutionary trajectory of a predator-prey system.

PMID- 19154364
TI  - Purging the genome with sexual selection: reducing mutation load through
      selection on males.
AB  - Healthy males are likely to have higher mating success than unhealthy males
      because of differential expression of condition-dependent traits such as mate
      searching intensity, fighting ability, display vigor, and some types of
      exaggerated morphological characters. We therefore expect that most new mutations
      that are deleterious for overall fitness may also be deleterious for male mating
      success. From this perspective, sexual selection is not limited to influencing
      those genes directly involved in exaggerated morphological traits but rather
      affects most, if not all, genes in the genome. If true, sexual selection can be
      an important force acting to reduce the frequency of deleterious mutations and,
      as a result, mutation load. We review the literature and find various forms of
      indirect evidence that sexual selection helps to eliminate deleterious mutations.
      However, direct evidence is scant, and there are almost no data available to
      address a key issue: is selection in males stronger than selection in females? In
      addition, the total effect of sexual selection on mutation load is complicated by
      possible increases in mutation rate that may be attributable to sexual selection.
      Finally, sexual selection affects population fitness not only through mutation
      load but also through sexual conflict, making it difficult to empirically measure
      how sexual selection affects load. Several lines of enquiry are suggested to
      better fill large gaps in our understanding of sexual selection and its effect on
      genetic load.

PMID- 19154365
TI  - Modeling three-dimensional morphological structures using spherical harmonics.
AB  - Quantifying morphological shape is a fundamental issue in evolutionary biology.
      Recent technological advances (e.g., confocal microscopy, laser scanning,
      computer tomography) have made the capture of detailed three-dimensional (3D)
      morphological structure easy and cost-effective. In this article, we develop a 3D
      analytic framework (SPHARM-spherical harmonics) for modeling the shapes of
      complex morphological structures from continuous surface maps that can be
      produced by these technologies. Because the traditional SPHARM methodology has
      limitations in several of its processing steps, we present new algorithms for two
      SPHARM processing steps: spherical parameterization and SPHARM registration.
      These new algorithms allow for the numerical characterization of a much larger
      class of 3D models. We demonstrate the effectiveness of the method by applying it
      to modeling the cerci of Enallagma damselflies.

PMID- 19154366
TI  - Divergent selection, not life-history plasticity via food limitation, drives
      morphological divergence between predator regimes in Gambusia hubbsi.

PMID- 19154367
TI  - Male dominance, female mate choice, and intersexual conflict in the rose
      bitterling (Rhodeus ocellatus).
AB  - An intersexual conflict arises when males and females differ in their
      reproductive interests. Although experimental studies have shown that females
      often mate with dominant males, it may not always be in the interest of a female
      to do so. Here we investigated the impact of male dominance on female mate choice
      and offspring growth and survival in the rose bitterling (Rhodeus ocellatus), a
      freshwater fish with a resource-based mating system. Three experimental mating
      trials were conducted using males of known dominance rank, but with different
      levels of constraint on male behavior. Thus, females were able to choose among;
      (1) males that were isolated from each other; (2) males that could see and smell
      each other, but could not directly interact; (3) males that could interact fully.
      Using a combination of behavioral observation and parentage analyses it was shown
      that female preferences did not correspond with male dominance and that male
      aggression and dominance constrained female mate choice, resulting in a potential
      intersexual conflict. The survival of offspring to independence was significantly
      correlated with female mate preferences, but not with male dominance. A lack of
      strong congruence in female preference for males suggested a role for parental
      haplotype compatibility in mate choice.

PMID- 19154368
TI  - Contemporary isolation-by-distance, but not isolation-by-time, among demes of
      European Grayling (Thymallus thymallus, Linnaeus) with recent common ancestors.
AB  - The development of isolation by distance (IBD) and isolation by time (IBT) was
      contrasted among demes of European grayling (Thymallus thymallus) that have
      diverged within the last 25 generations following colonization of a lake
      (Lesjaskogsvatnet). We find low but significant levels of genetic differentiation
      among spawning tributaries and a pattern of IBD among them. We do not, however,
      find evidence for IBT despite an up to four-week difference in spawning date
      between "warm/early" and "cold/late" spawning demes and differences in the
      incubation temperatures experienced by offspring. It appears that IBD has
      developed more rapidly than IBT in this system and that adaptive divergence has
      been initiated in the absence of IBT. Although analysis of selected loci could
      reveal reduced recombination in parts of the genome associated with temporal
      divergence, our analysis of neutral genetic data suggests that IBD is a more
      important isolating mechanism in the early stages of adaptive divergence in
      European grayling.

PMID- 19154369
TI  - Predation, food limitation, phenotypic plasticity and life-history variation in
      Gambusia hubbsi.

PMID- 19154370
TI  - Leaf shape evolution in the South African genus Pelargonium L'Her. (Geraniaceae).
AB  - Leaf shapes reflect complex assemblages of shape-determining elements, yet
      evolutionary studies tend to treat leaf shape as a single attribute, for example
      cordate or linear. As with all complex structures, individual elements of a leaf
      could theoretically evolve independently and at different rates to the extent
      permitted by genetic and functional limitations. We examined relative
      evolutionary lability of shape-determining elements in the highly diverse South
      African plant genus Pelargonium (Geraniaceae). We used SIMMAP to calculate
      Bayesian posterior probabilities for ancestral states of leaf-shape characters
      for major nodes across multiple phylogenetic trees. Trees were derived from a
      Bayesian analysis of DNA sequence data from four partitions. We found that shape
      elements differed in rates of character-state transformations across the tree.
      Leaf base, apex, and overall outline had low rates. Transformations in venation
      occurred at slightly higher rates and were associated with shifts in venation
      among major clades. Leaf margin type and overall leaf size showed intermediate
      rates, whereas high rates were observed in the extent of lamina lobing and
      functional leaf size. The results indicate that suites of elements characteristic
      of the recently evolved xerophytic lineage, for example pinnate venation,
      dissected lamina, and entire margins, were acquired piecemeal over nested levels
      of the phylogeny.

PMID- 19154371
TI  - Sexual selection accelerates the elimination of a deleterious mutant in
      Drosophila melanogaster.
AB  - Although theory indicates that indirect genetic benefits through mate choice
      should be widespread, empirical work has often either failed to detect the
      operation of such benefits or shown a net cost to the presence of sexual
      selection. We tested whether sexual selection can increase the speed with which a
      conditionally deleterious allele is removed from a laboratory population of
      Drosophila melanogaster. The alcohol dehydrogenase null allele (Adh-) confers
      slightly lower viability than wild-type alleles in the absence of ethanol but is
      lethal in homozygotes when ethanol comprises 6% of the medium. We tracked the
      frequency of this allele in artificially constructed populations reared at three
      different levels of ethanol (0%, 2%, and 4%) that either experienced sexual
      selection or did not. Loss of the deleterious Adh- allele was more rapid when
      sexual selection was allowed to act, especially in the presence of ethanol. We
      also quantified the strength of both nonsexual and sexual selection against the
      Adh- allele using maximum-likelihood estimation. In contrast to recent
      experiments employing monogamy/polygamy designs, our results demonstrate a
      fitness benefit to sexual selection. This is consistent with the operation of
      good-genes female choice.

PMID- 19154372
TI  - Evolution of incompatibility-inducing microbes in subdivided host populations.
AB  - Many insects, other arthropods, and nematodes harbor maternally inherited
      bacteria inducing "cytoplasmic incompatibility" (CI), reduced egg hatch when
      infected males mate with uninfected females. Although CI drives the spread of
      these microbes, selection on alternative, mutually compatible strains in
      panmictic host populations does not act directly on CI intensity but favors
      higher "effective fecundity," the number of infected progeny an infected female
      produces. We analyze the consequences of host population subdivision using
      deterministic and stochastic models. In subdivided populations, effective
      fecundity remains the primary target of selection. For strains of equal effective
      fecundity, if population density is regulated locally (i.e., "soft selection"),
      variation among patches in infection frequencies may induce change in the
      relative frequencies of the strains. However, whether this change favors stronger
      incompatibility depends on initial frequencies. Demographic fluctuations maintain
      frequency variation that tends to favor stronger incompatibility. However, this
      effect is weak; even with small patches, minute increases in effective fecundity
      can offset substantial decreases in CI intensity. These results are insensitive
      to many details of host life cycle and migration and to systematic outbreeding or
      inbreeding within patches. Selection acting through transfer between host species
      may be required to explain the prevalence of CI.

PMID- 19154373
TI  - Limited dispersal, budding dispersal, and cooperation: an experimental study.
AB  - Numerous theoretical studies have investigated how limited dispersal may provide
      an explanation for the evolution of cooperation, by leading to interactions
      between relatives. However, despite considerable theoretical attention, there has
      been a lack of empirical tests. In this article, we test how patterns of
      dispersal influence the evolution of cooperation, using iron-scavenging in the
      bacterium Pseudomonas aeruginosa as our cooperative trait. We found that
      relatively limited dispersal does not favor cooperation. The reason for this is
      that although limited dispersal increases the relatedness between interacting
      individuals, it also leads to increased local competition for resources between
      relatives. This result supports Taylor's prediction that in the simplest possible
      scenario, the effects of increased relatedness and local competition exactly
      cancel out. In contrast, we show that one way for cooperation to be favored is if
      individuals disperse in groups (budding dispersal), because this maintains high
      relatedness while reducing local competition between relatives (relatively global
      competition).

PMID- 19154374
TI  - A maternal effect mediates rapid population divergence and character displacement
      in spadefoot toads.
AB  - Despite long-standing interest in character displacement, little is known of its
      underlying proximate causes. Here, we explore the role of maternal effects in
      character displacement. We specifically investigated whether differences in
      maternal body condition mediate divergence in the expression of resource-use
      traits between populations of spadefoot toads (Spea multiplicata) that occur in
      sympatry with a heterospecific competitor and those that occur in allopatry. In
      sympatry, S. multiplicata is forced by its competitor onto a less profitable
      resource. As a result, sympatric females mature in poorer condition and invest
      less into offspring. Consequently, their offspring produce a resource-use
      phenotype that minimizes competition with the other species and that also differs
      from the phenotype produced in allopatry. These differences in trait expression
      between allopatry and sympatry disappear once mothers are equilibrated in body
      condition in the laboratory. Thus, a condition-dependent maternal effect mediates
      population divergence and character displacement. Such effects potentially buffer
      populations from extinction (via competitive exclusion) while genetic changes
      accumulate, which produce divergent traits in the absence of the maternal effect.
      Maternal effects may therefore often be important in determining the initial
      direction and rate of evolution during the early stages of character
      displacement.

PMID- 19154375
TI  - Heterozygosity-fitness correlations revealed by neutral and candidate gene
      markers in roe deer from a long-term study.
AB  - Heterozygosity-fitness correlations (HFCs) are increasingly reported but the
      underlying mechanisms causing HFCs are generally poorly understood. Here, we test
      for HFCs in roe deer (Capreolus capreolus) using 22 neutral microsatellites
      widely distributed in the genome and four microsatellites in genes that are
      potentially under selection. Juvenile survival was used as a proxy for individual
      fitness in a population that has been intensively studied for 30 years in
      northeastern France. For 222 juveniles, we computed two measures of genetic
      diversity: individual heterozygosity (H), and mean d(2) (relatedness of parental
      genomes). We found a relationship between genetic diversity and fitness both for
      the 22 neutral markers and two candidate genes: IGF1 (Insulin-like Growth Factor
      I) and NRAMP (natural resistance-associated macrophage protein). Statistical
      evidence and the size of genetic effects on juvenile survival were comparable to
      those reported for early development and cohort variation, suggesting a
      substantial influence of genetic components on fitness in this roe deer
      population. For the 22 neutral microsatellites, a correlation with fitness was
      revealed for mean d(2), but not for H, suggesting a possible outbreeding
      advantage. This heterosis effect could have been favored by introduction of
      genetically distant (Hungarian) roe deer to the population in recent times and,
      possibly, by the structuring of the population into distinct clans. The locus
      specific correlations with fitness may be driven by growth rate advantages and
      resistance to diseases known to exist in the studied population. Our analyses of
      neutral and candidate gene markers both suggest that the observed HFCs are likely
      mainly due to linkage with dominant or overdominant loci that affect fitness
      ("local" effect) rather than to a genome-wide relationship with homozygosity due
      to inbreeding ("general" effect).

PMID- 19154376
TI  - On the evolution of differentiated multicellularity.
AB  - Most conspicuous organisms are multicellular and most multicellular organisms
      develop somatic cells to perform specific, nonreproductive tasks. The ubiquity of
      this division of labor suggests that it is highly advantageous. In this article I
      present a model to study the evolution of specialized cells. The model allows for
      unicellular and multicellular organisms that may contain somatic (terminally
      differentiated) cells. Cells contribute additively to a quantitative trait. The
      fitness of the organism depends on this quantitative trait (via a benefit
      function), the size of the organism, and the number of somatic cells. The model
      allows one to determine when somatic cells are advantageous and to calculate the
      optimum number (or fraction) of reproductive cells. I show that the fraction of
      reproductive cells is always surprisingly high. If somatic cells are very small,
      they can outnumber reproductive cells but their biomass is still less than the
      biomass of reproductive cells. I discuss the biology of primitive multicellular
      organisms with respect to the model predictions. I find a good agreement and
      outline how this work can be used to guide further quantitative studies of
      multicellularity.

PMID- 19154377
TI  - Effects of clonality in multiple infections on the life-history strategy of the
      trematode Coitocaecum parvum in its amphipod intermediate host.
AB  - Theoretical models predict that genetic relatedness affects the competition
      within and between parasite clonal groups sharing a common host. Here, we studied
      natural and experimental multiple infections of the trematode Coitocaecum parvum
      in its intermediate host. We focused on the effects of clonality on the life
      history strategy of parasites competing for resources. Coitocaecum parvum can
      either delay maturation until its amphipod host is ingested by a definitive host,
      or adopt a progenetic strategy and reproduce inside the amphipod. Within a common
      host, clonal parasites were more likely to adopt identical life-history
      strategies than different genetic clones, both in natural and experimental
      infections. However, when timing of infection and other factors were controlled
      experimentally, parasites sharing a host were likely to adopt identical
      strategies regardless of their clonal identity, although pairs of clones were
      more likely to adopt progenesis than pairs of nonclones. The asymmetries in
      relative size and egg production between coinfecting parasites adopting the same
      life-history strategy were slightly, but not significantly, higher between
      different clones than identical clones. Our results suggest that the dynamics of
      competition between coinfecting parasites, although influenced by numerous
      external factors, is also modulated by genetic relatedness among parasites.

PMID- 19154378
TI  - Sex-linkage of sexually antagonistic genes is predicted by female, but not male,
      effects in birds.
AB  - Evolutionary theory predicts that sexually antagonistic loci will be
      preferentially sex-linked, and this association can be empirically testes with
      data on sex-biased gene expression with the assumption that sex-biased gene
      expression represents the resolution of past sexual antagonism. However,
      incomplete dosage compensating mechanisms and meiotic sex chromosome inactivation
      have hampered efforts to connect expression data to theoretical predictions
      regarding the genomic distribution of sexually antagonistic loci in a variety of
      animals. Here we use data on the underlying regulatory mechanism that produce
      expression sex-bias to test the genomic distribution of sexually antagonistic
      genes in chicken. Using this approach, which is free from problems associated
      with the lack of dosage compensation in birds, we show that female-detriment
      genes are significantly overrepresented on the Z chromosome, and female-benefit
      genes underrepresented. By contrast, male-effect genes show no over- or
      underrepresentation on the Z chromosome. These data are consistent with a
      dominant mode of inheritance for sexually antagonistic genes, in which male
      benefit coding mutations are more likely to be fixed on the Z due to stronger
      male-specific selective pressures. After fixation of male-benefit alleles,
      regulatory changes in females evolve to minimize antagonism by reducing female
      expression.

PMID- 19154379
TI  - Island biogeography of Galapagos lava lizards (Tropiduridae: Microlophus):
      species diversity and colonization of the archipelago.
AB  - The "lava lizards" (Microlophus) are distributed throughout the Galapagos
      Archipelago, and consist of radiations derived from two independent
      colonizations. The "Eastern Radiation" includes M. bivittatus and M. habeli
      endemic to San Cristobal and Marchena Islands. The "Western Radiation" includes
      five to seven historically recognized species distributed across almost the
      entire Archipelago. We combine dense geographic sampling and multilocus sequence
      data to estimate a phylogenetic hypothesis for the Western Radiation, to delimit
      species boundaries in this radiation, and to estimate a time frame for
      colonization events. Our phylogenetic hypothesis rejects two earlier topologies
      for the Western Radiation and paraphyly of M. albemarlensis, while providing
      strong support for single colonizations on each island. The colonization history
      implied by our phylogeny is consistent with general expectations of an east-to
      west route predicted by the putative age of island groups, and prevailing ocean
      currents in the Archipelago. Additionally, combined evidence suggests that M.
      indefatigabilis from Santa Fe should be recognized as a full species. Finally,
      molecular divergence estimates suggest that the two colonization events likely
      occurred on the oldest existing islands, and the Western Radiation represents a
      recent radiation that, in most cases, has produced species that are considerably
      younger than the islands they inhabit.

PMID- 19154380
TI  - Phylogenetic analysis of the evolutionary correlation using likelihood.
AB  - Many evolutionary processes can lead to a change in the correlation between
      continuous characters over time or on different branches of a phylogenetic tree.
      Shifts in genetic or functional constraint, in the selective regime, or in some
      combination thereof can influence both the evolution of continuous traits and
      their relation to each other. These changes can often be mapped on a phylogenetic
      tree to examine their influence on multivariate phenotypic diversification. We
      propose a new likelihood method to fit multiple evolutionary rate matrices (also
      called evolutionary variance-covariance matrices) to species data for two or more
      continuous characters and a phylogeny. The evolutionary rate matrix is a matrix
      containing the evolutionary rates for individual characters on its diagonal, and
      the covariances between characters (of which the evolutionary correlations are a
      function) elsewhere. To illustrate our approach, we apply the method to an
      empirical dataset consisting of two features of feeding morphology sampled from
      28 centrarchid fish species, as well as to data generated via phylogenetic
      numerical simulations. We find that the method has appropriate type I error,
      power, and parameter estimation. The approach presented herein is the first to
      allow for the explicit testing of how and when the evolutionary covariances
      between characters have changed in the history of a group.

PMID- 19154381
TI  - Correlated evolution of sexual system and life-history traits in mosses.
AB  - In mosses, separate and combined sexes are evolutionarily labile, yet factors
      selecting for this variation are unknown. In this study, we investigate
      phylogenetic correlations between sexual system and five life-history traits
      (asexual reproduction, chromosome number, gametophore length, spore size, and
      seta length). We assigned states to species on a large-scale phylogeny of mosses
      and used maximum likelihood analyses to test for the correlations and investigate
      the sequence of trait acquisition. Mosses in lineages with separate sexes were
      significantly more likely to be large, whereas those in lineages with combined
      sexes had higher chromosome numbers. Moreover, evolutionary transitions to
      separate sexes were more likely to occur in lineages with small spores. There was
      no support for a correlation between asexual reproduction and separate sexes.
      These results suggest that sexual system evolution is influenced by traits
      affecting mate availability and the dispersal of gametes and spores, and provides
      evidence for the existence of syndromes of life-history traits in mosses.

PMID- 19154382
TI  - Reversing mother's curse: selection on male mitochondrial fitness effects.
AB  - Many essential organelles and endosymbionts exhibit a strict matrilineal pattern
      of inheritance. The absence of paternal transmission of such extranuclear
      components is thought to preclude a response to selection on their effects on
      male viability and fertility. We overturn this dogma by showing that two
      mechanisms, inbreeding and kin selection, allow mitochondria to respond to
      selection on both male viability and fertility. Even modest levels of inbreeding
      allow such a response to selection when there are direct fitness effects of
      mitochondria on male fertility because inbreeding associates male fertility
      traits with mitochondrial matrilines. Male viability effects of mitochondria are
      also selectable whenever there are indirect fitness effects of males on the
      fitness of their sisters. When either of these effects is sufficiently strong, we
      show that there are conditions that allow the spread of mitochondria with direct
      effects that are harmful to females, contrary to standard expectation. We discuss
      the implications of our findings for the evolution of organelles and
      endosymbionts and genomic conflict.

PMID- 19154383
TI  - Forelimb posture in dinosaurs and the evolution of the avian flapping flight
      stroke.
AB  - Ontogenetic and behavioral studies using birds currently do not document the
      early evolution of flight because birds (including juveniles) used in such
      studies employ forelimb oscillation frequencies over 10 Hz, forelimb stroke
      angles in excess of 130 degrees , and possess uniquely avian flight musculatures.
      Living birds are an advanced morphological stage in the development of flapping
      flight. To gain insight into the early stages of flight evolution (i.e.,
      prebird), in the absence of a living analogue, a new approach using Strouhal
      number was used. Strouhal number is a nondimensional number that describes the
      relationship between wing-stroke amplitude (A), wing-beat frequency (f), and
      flight speed (U). Calculations indicated that even moderate wing movements are
      enough to generate rudimentary thrust and that a propulsive flapping flight
      stroke could have evolved via gradual incremental changes in wing movement and
      wing morphology. More fundamental to the origin of the avian flapping flight
      stroke is the question of how a symmetrical forelimb posture-required for gliding
      and flapping flight-evolved from an alternating forelimb motion, evident in all
      extant bipeds when running except birds.

PMID- 19154384
TI  - Contrasting patterns of spatial genetic structure in sympatric rock-dwelling
      cichlid fishes.
AB  - The cichlid fish of Lake Tanganyika in Eastern Africa are a celebrated example of
      both ecological and species diversification. Because population subdivision is
      likely to play an important role in the speciation process, understanding how
      habitat features interact with species' demographic, behavioral and ecological
      attributes to influence gene flow and population divergence may help explain the
      causes of high species richness in this and other systems. Here, we test the
      roles of isolation-by-habitat and isolation-by-distance in generating fine-scale
      population genetic structure in three sympatric species of habitat-restricted
      cichlids in Lake Tanganyika. Using multilocus microsatellite genotypes, we
      contrast patterns of population differentiation in these habitat specialists
      along a mosaic coastline of both favorable and unfavorable habitat. Despite their
      close phylogenetic relationship and shared habitat affinity, these species show
      striking differences in their pattern of genetic subdivision within the same
      geographical region, suggesting substantially different patterns of gene flow. In
      particular, two trophically specialized species exhibit much more restricted gene
      flow over sandy habitat than a trophically opportunistic species. This result
      suggests that ecological and behavioral traits have a strong influence on the
      scale and degree of population subdivision, a finding that has potentially
      important implications for understanding differential propensities for
      diversification among lineages and phylogenetic patterns of diversity.

PMID- 19154385
TI  - Asymmetric viability of reciprocal-cross hybrids between crested and marbled
      newts (Triturus cristatus and T. Marmoratus).
AB  - Hybridization between divergent lineages often results in reduced hybrid
      viability. Here we report findings from a series of independent molecular
      analyses over several seasons on four life stages of F1 hybrids between the newts
      Triturus cristatus and T. marmoratus. These two species form a bimodal hybrid
      zone of broad overlap in France, with F1 hybrids making up about 4% of the adult
      population. We demonstrate strong asymmetry in the direction of the cross, with
      one class (cristatus-mothered) making up about 90% of F1 hybrids. By analyzing
      embryos and hatchlings, we show that this asymmetry is not due to prezygotic
      effects, as both classes of hybrid embryos are present at similar frequencies,
      implicating differential selection on the two hybrid classes after hatching.
      Adult F1 hybrids show a weak Haldane effect overall, with a 72% excess of
      females. The rarer marmoratus-mothered class, however, consists entirely of
      males. The absence of females from this class of adult F1 hybrids is best
      explained by an incompatibility between the cristatus X chromosome and marmoratus
      cytoplasm. It is thus important to distinguish the two classes of reciprocal
      cross hybrids before making general statements about whether Haldane's rule is
      observed.

PMID- 19154386
TI  - Evolutionary and biogeographic origins of high tropical diversity in old world
      frogs (Ranidae).
AB  - Differences in species richness between regions are ultimately explained by
      patterns of speciation, extinction, and biogeographic dispersal. Yet, few studies
      have considered the role of all three processes in generating the high
      biodiversity of tropical regions. A recent study of a speciose group of
      predominately New World frogs (Hylidae) showed that their low diversity in
      temperate regions was associated with relatively recent colonization of these
      regions, rather than latitudinal differences in diversification rates (rates of
      speciation-extinction). Here, we perform parallel analyses on the most species
      rich group of Old World frogs (Ranidae; approximately 1300 species) to determine
      if similar processes drive the latitudinal diversity gradient. We estimate a time
      calibrated phylogeny for 390 ranid species and use this phylogeny to analyze
      patterns of biogeography and diversification rates. As in hylids, we find a
      strong relationship between the timing of colonization of each region and its
      current diversity, with recent colonization of temperate regions from tropical
      regions. Diversification rates are similar in tropical and temperate clades,
      suggesting that neither accelerated tropical speciation rates nor greater
      temperate extinction rates explain high tropical diversity in this group.
      Instead, these results show the importance of historical biogeography in
      explaining high species richness in both the New World and Old World tropics.

PMID- 19154387
TI  - Evolutionary epidemiology and the dynamics of adaptation.
AB  - The mean fitness of a population, often equal to its growth rate, measures its
      level of adaptation to particular environmental conditions. A better
      understanding of the evolution of mean fitness could thus provide a natural link
      between evolution and demography. Yet, after the seminal work of Fisher and its
      renowned "fundamental theorem of natural selection," the dynamics of mean fitness
      has attracted little attention, and mostly from theoretical population
      geneticists. Here we analyze the dynamics of mean fitness in the context of host
      parasite interactions. We illustrate the potential relevance of this analysis
      under different scenarios ranging from a simple situation in which a parasite
      evolves in a homogeneous host population to a more complex one with host-parasite
      coevolution. In each case, we contrast the effects of natural selection,
      recurrent mutations, and the change of the biotic environment, on the dynamics of
      adaptation. Decoupling these three components helps elucidate the interplay
      between evolutionary and ecological dynamics. In particular, it offers new
      perspectives on situations leading to evolutionary suicide. As mean fitness is an
      easily measurable quantity in microbial systems, this analysis provides new ways
      to track the dynamics of adaptation in experimental evolution and coevolution
      studies.

PMID- 19154388
TI  - Dynamics and genetic structure of Argentine ant supercolonies in their native
      range.
AB  - Some introduced ant populations have an extraordinary social organization, called
      unicoloniality, whereby individuals mix freely within large supercolonies. We
      investigated whether this mode of social organization also exists in native
      populations of the Argentine ant Linepithema humile. Behavioral analyses revealed
      the presence of 11 supercolonies (width 1 to 515 m) over a 3-km transect. As in
      the introduced range, there was always strong aggression between but never within
      supercolonies. The genetic data were in perfect agreement with the behavioral
      tests, all nests being assigned to identical supercolonies with the different
      methods. There was strong genetic differentiation between supercolonies but no
      genetic differentiation among nests within supercolonies. We never found more
      than a single mitochondrial haplotype per supercolony, further supporting the
      view that supercolonies are closed breeding units. Genetic and chemical distances
      between supercolonies were positively correlated, but there were no other
      significant associations between geographic, genetic, chemical, and behavioral
      distances. A comparison of supercolonies sampled in 1999 and 2005 revealed a very
      high turnover, with about one-third of the supercolonies being replaced yearly.
      This dynamic is likely to involve strong competition between supercolonies and
      thus act as a potent selective force maintaining unicoloniality over evolutionary
      time.

PMID- 19154389
TI  - Background matching and color-change plasticity in colonizing freshwater sculpin
      populations following rapid deglaciation.
AB  - Anthropogenic-induced change is forcing organisms to shift their distributions
      and colonize novel habitats at an increasing rate, which leads to complex
      interactions among evolutionary processes. Coastrange sculpin (Cottus aleuticus)
      have colonized recently deglaciated streams of Glacier Bay in Alaska within the
      last 220 years. We examined divergence among populations in background matching
      coloration and tested the hypothesis that observed variation is due to
      morphological color plasticity. To examine how color-change plasticity has
      interacted with other evolutionary processes, we also determined the influence of
      colonization on neutral genetic diversity. We observed clinal variation in
      substrate-matching fish color along the chronological continuum of streams.
      Microsatellites provided little evidence of genetic subdivision among sculpin
      populations. Fish color was significantly correlated to substrate color, but was
      not correlated to neutral population genetic structure. Furthermore, a laboratory
      experiment revealed that morphological color plasticity could explain much, but
      not all, of the observed fish color divergence. Our study demonstrates that
      sculpin in Glacier Bay have colonized and adapted to recently deglaciated habitat
      and suggests that color change plasticity has aided in this process. This
      research, therefore, highlights the important role phenotypic plasticity may play
      in the adaptation of species to rapid climate change.

PMID- 19154390
TI  - Piscivory limits diversification of feeding morphology in centrarchid fishes.
AB  - Proximity to an adaptive peak influences a lineage's potential to diversify. We
      tested whether piscivory, a high quality but functionally demanding trophic
      strategy, represents an adaptive peak that limits morphological diversification
      in the teleost fish clade, Centrarchidae. We synthesized published diet data and
      applied a well-resolved, multilocus and time-calibrated phylogeny to reconstruct
      ancestral piscivory. We measured functional features of the skull and performed
      principal components analysis on species' values for these variables. To assess
      the role of piscivory on morphological diversification, we compared the fit of
      several models of evolution for each principal component (PC), where model
      parameters were allowed to vary between lineages that differed in degree of
      piscivory. According to the best-fitting model, two adaptive peaks influenced PC
      1 evolution, one peak shared between highly and moderately piscivorous lineages
      and another for nonpiscivores. Brownian motion better fit PCs 2, 3, and 4, but
      the best Brownian models infer a slow rate of PC 2 evolution shared among all
      piscivores and a uniquely slow rate of PC 4 evolution in highly piscivorous
      lineages. These results suggest that piscivory limits feeding morphology
      diversification, but this effect is most severe in lineages that exhibit an
      extreme form of this diet.

PMID- 19154391
TI  - Evolution of genetic integration between dispersal and colonization ability in a
      bird.
AB  - Discrete behavioral strategies comprise a suite of traits closely integrated in
      their expression with consistent natural selection for such coexpression leading
      to developmental and genetic integration of their components. However, behavioral
      traits are often also selected to respond rapidly to changing environments, which
      should both favor their context-dependent expression and inhibit evolution of
      genetic integration with other, less flexible traits. Here we use a
      multigeneration pedigree and long-term data on lifetime fitness to test whether
      behaviors comprising distinct dispersal strategies of western bluebirds-a species
      in which the propensity to disperse is functionally integrated with aggressive
      behavior-are genetically correlated. We further investigated whether selection
      favors flexibility in the expression of aggression in relation to current social
      context. We found a significant genetic correlation between aggression and
      dispersal that is concordant with consistent selection for coexpression of these
      behaviors. To a limited extent, individuals modified their aggression to match
      their mate; however, we found no fitness consequences on such adjustments. These
      results introduce a novel way of viewing behavioral strategies, where flexibility
      of behavior, while often aiding an organism's fit in its current environment, may
      be limited and thereby enable integration with less flexible traits.

PMID- 19154392
TI  - Pollinator-mediated selection on floral display and flowering time in the
      perennial herb Arabidopsis lyrata.
AB  - The evolution of floral display and flowering time in animal-pollinated plants is
      commonly attributed to pollinator-mediated selection. Yet, the causes of
      selection on flowering phenology and traits contributing to floral display have
      rarely been tested experimentally in natural populations. We quantified
      phenotypic selection on morphological and phenological characters in the
      perennial, outcrossing herb Arabidopsis lyrata in two years using female
      reproductive success as a proxy of fitness. To determine whether selection on
      floral display and flowering phenology can be attributed to interactions with
      pollinators, selection was quantified both for open-pollinated controls and for
      plants receiving supplemental hand-pollination. We documented directional
      selection for many flowers, large petals, late start of flowering, and early end
      of flowering. Seed output was pollen-limited in both years and supplemental hand
      pollination reduced the magnitude of selection on number of flowers, and reversed
      the direction of selection on end of flowering. The results demonstrate that
      interactions with pollinators may affect the strength of selection on floral
      display and the direction of selection on phenology of flowering in natural plant
      populations. They thus support the contention that pollinators can drive the
      evolution of both floral display and flowering time.

PMID- 19154393
TI  - Intergenic exchange, geographic isolation, and the evolution of bioluminescent
      color for Pyrophorus click beetles.
AB  - Gene duplication is an evolutionary process in which the emergent property of the
      whole can become greater and different than the sum of its parts. One potential
      outcome for gene duplication is for loci to evolve different, yet related
      functions. In this case, intergenic exchange can shuffle blocks of differentiated
      nucleotides between paralogues to create new alleles and phenotypes rather than
      simply homogenize loci. Bioluminescent click beetles in the genus Pyrophorus
      (Coleoptera: Elateridae) provide an opportunity to explore the creative potential
      of intergenic exchange for gene family evolution. Pyrophorus beetles bioluminesce
      different light colors from a pair of dorsal light organs and a ventral light
      organ. The light organs are under the separate genetic control of dorsal and
      ventral luciferase loci. Here, we report that intergenic exchange is common
      between dorsal and ventral loci for beetles from Jamaica (P. plagiophthalamus),
      the Dominican Republic (P. mellifluous), Belize (P. luscus), and Trinidad (P.
      noctilucus). We also present evidence that periods of past geographic isolation
      for beetles on Jamaica, probably acting in concert with selection, built
      differentiated blocks of substitutions within dorsal and ventral P.
      plagiophthalamus luciferase loci. Gene flow and intergenic exchange subsequently
      shuffled these substitutions between dorsal and ventral loci to produce new color
      phenotypes on Jamaica, including a yellow-green polymorphism. We discuss the
      possibility of a previously unrecognized emergent evolutionary property of
      intergenic exchange for luciferase involving cycles of bioluminescent color
      change related to differences in selective constrains acting on dorsal versus
      ventral loci. We also explore whether intergenic exchange may commonly create
      novel variation and the potential for cyclic evolution in other multigene family
      systems.

PMID- 19154394
TI  - The evolution of strong reproductive isolation.
AB  - Felsenstein distinguished two ways by which selection can directly strengthen
      isolation. First, a modifier that strengthens prezygotic isolation can be favored
      everywhere. This fits with the traditional view of reinforcement as an adaptation
      to reduce deleterious hybridization by strengthening assortative mating. Second,
      selection can favor association between different incompatibilities, despite
      recombination. We generalize this "two allele" model to follow associations among
      any number of incompatibilities, which may include both assortment and hybrid
      inviability. Our key argument is that this process, of coupling between
      incompatibilities, may be quite different from the usual view of reinforcement:
      strong isolation can evolve through the coupling of any kind of incompatibility,
      whether prezygotic or postzygotic. Single locus incompatibilities become coupled
      because associations between them increase the variance in compatibility, which
      in turn increases mean fitness if there is positive epistasis. Multiple
      incompatibilities, each maintained by epistasis, can become coupled in the same
      way. In contrast, a single-locus incompatibility can become coupled with loci
      that reduce the viability of haploid hybrids because this reduces harmful
      recombination. We obtain simple approximations for the limits of tight linkage,
      and strong assortment, and show how assortment alleles can invade through
      associations with other components of reproductive isolation.

PMID- 19154395
TI  - The evolution of body shape in response to habitat: is reproductive output
      reduced in flat lizards?
AB  - Body size and shape are primary determinants of reproductive output in a variety
      of taxa, so selection favoring specific body sizes and shapes may, in turn, have
      a direct affect on reproductive output, and ultimately fitness. In reptiles,
      species that occupy rocky habitats are often flattened, a morphological character
      that aids locomotion and life on rocks, but which may constrain reproductive
      output by reducing the amount of abdominal space available to fill with eggs or
      offspring. Using 20 species of tropical skink from a wide range of habitats, we
      quantified habitat use, body height, body volume, and reproductive output, to
      determine whether the evolution of a flattened body was correlated with a
      reduction in abdominal volume, and, in turn, with reduced reproductive output. In
      this group of lizards, the occupation of rocky habitats has led (1) to the
      evolution of a flattened body, and this shift in body shape has (2) caused a
      reduction in abdominal volume. Despite this reduction in abdominal volume
      reproductive output was unaffected, as flatter species compensate by being more
      "full" of eggs. Thus, we demonstrate that morphological adaptation for enhanced
      performance in specific habitats did not cause a reduction in instantaneous
      reproductive output.

PMID- 19154397
TI  - Gamma frequency SSVEP components differentiate children with febrile seizures
      from normal controls.
AB  - Gamma band electroencephalography (EEG) abnormalities have been reported in
      patients with epilepsy. We aimed to investigate whether patients with febrile
      seizures (FS) show abnormalities of the gamma frequency steady-state visual
      evoked potential (SSVEP) components evoked by intermittent photic stimulation
      (IPS). We analyzed the magnitude and phase alignment of the 50-100 Hz SSVEP
      components elicited by IPS from 12 FS patients, 5 siblings of FS patients, and 15
      control children between 6 and 36 months of age. Patients with FS showed
      significantly higher SSVEP magnitude and phase alignment values when compared to
      both the siblings and control groups. Detected abnormalities could either
      represent the direct consequence of seizures or indicate a preexisting tendency
      to hypersynchrony in FS patients. Future prospective studies could assess whether
      SSVEP abnormalities are associated with complex rather than simple FS, or have a
      prognostic value for the development of epilepsy following FS.

PMID- 19154398
TI  - Seizure recurrence risk following a first seizure in neurologically normal
      children.
AB  - PURPOSE: To define seizure recurrence rates in normal children who had had a
      single seizure and to define electroencephalography (EEG) or magnetic resonance
      imaging (MRI) utility in predicting seizure recurrence. METHODS: We studied 150
      children (6 to 14 years) with a first afebrile, unprovoked seizure. Inclusion
      criteria were: Normal physical and neurological examination, undergone EEG and
      MRI studies of the brain, and followed for at least 27 months. These children
      participated in an ongoing prospective study of new onset seizures in childhood.
      RESULTS: The seizure recurrence rate was 66.4%. An abnormal EEG had no
      association with seizure recurrence at 9, 18, or 27 months (p = 0.1806, p =
      0.2792, and p = 0.2379, respectively). A "significant" MRI abnormality, which
      occurred in 16.0% of patients, was associated with an increased seizure
      recurrence risk at 9 months (p = 0.0389) but not at 18 or 27 months. DISCUSSION:
      EEG findings poorly predict recurrence after a single seizure. The high rate of
      MRI abnormalities suggests that MRI may need consideration as a routine test to
      evaluate epilepsy in normal children.

PMID- 19154399
TI  - Workshop on idiopathic generalized epilepsies: Bridging basic science and
      clinical research (October 3-6, 2007; Antalya, Turkey).

PMID- 19154401
TI  - Ablation of p120-catenin enhances invasion and metastasis of human lung cancer
      cells.
AB  - p120-catenin, a member of the Armadillo gene family, has emerged as both a master
      regulator of cadherin stability and an important modulator of small GTPase
      activities. Therefore, it plays novel roles in tumor malignant phenotype, such as
      invasion and metastasis. We have reported previously that abnormal expression of
      p120-catenin is associated with lymph node metastasis in lung squamous cell
      carcinomas (SCC) and adenocarcinomas. To investigate the role and possible
      mechanism of p120-catenin in lung cancer, we knocked down p120-catenin using
      small interfering RNA (siRNA). We found that ablation of p120-catenin reduced the
      levels of E-cadherin and beta-catenin proteins, as well as the mRNA of beta
      catenin. Furthermore, p120-catenin depletion inactivated RhoA, but increased the
      activity of Cdc42 and Rac1, and promoted proliferation and the invasive ability
      of lung cancer cells both in vitro and in vivo. Our data reveal that p120-catenin
      gene knockdown enhances the metastasis of lung cancer cells, probably by either
      depressing cell-cell adhesion due to lower levels of E-cadherin and beta-catenin,
      or altering the activity of small GTPase, such as inactivation of RhoA and
      activation of Cdc42/Rac1.

PMID- 19154402
TI  - Polyinosinic-polycytidylic acid liposome induces human hepatoma cells apoptosis
      which correlates to the up-regulation of RIG-I like receptors.
AB  - Toll-like receptor 3 and RIG-I like receptors (RLRs; MDA5, RIG-I) are involved in
      cell growth inhibition and apoptosis. However, the toll-like receptor 3-related
      apoptotic pathway is insensitive to direct polyinosinic-polycytidylic acid (dsRNA
      analog) stimulation in hepatoma cells. To determine whether the strategy of
      transferring polyinosinic-polycytidylic acid into cells (polyinosinic
      polycytidylic acid-liposome) could induce apoptosis in hepatoma cells through
      cytoplasm receptors, we examined the responses of innate immune receptors RLRs
      and toll-like receptor 3 in response to different stimulation. We found that the
      apoptosis could exclusively be detected under polyinosinic-polycytidylic acid
      liposome stimulation, which involved the activation of the caspase pathway.
      Besides, the expression of RIG-I, MDA5, IFNbeta and interferon-stimulated gene 15
      was increased significantly at an early stage. Moreover, the growth inhibition of
      polyinosinic-polycytidylic acid-liposome was confirmed in a mouse model. Taken
      together, these results suggest polyinosinic-polycytidylic acid-liposome could be
      used as a potential apoptotic agent in hepatocellular carcinoma cells and imply a
      potential therapeutic strategy.

PMID- 19154403
TI  - V-PROLI/NO, a nitric oxide donor prodrug, protects liver cells from arsenic
      induced toxicity.
AB  - Inorganic arsenic shows great promise in human cancer chemotherapy, although
      hepatotoxicity is a major limiting side-effect. O(2)-Vinyl 1-[2
      (Carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (V-PROLI/NO) [Correction
      added after publication 19 December 2008: 1-[2-(Carboxylato)pyrrolidin-1
      yl]diazen-1-ium-1,2-diolate (V-PROLI/NO) was corrected to O(2)-Vinyl 1-[2
      (Carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (V-PROLI/NO)] is a nitric
      oxide (NO) donor prodrug that is metabolized by liver cytochromes P450 to release
      NO. Other NO-releasing agents have been shown to mitigate arsenic toxicity. Thus,
      the effects of V-PROLI/NO pretreatment on the toxicity of inorganic arsenic (as
      NaAsO(2)) were studied in vitro in a human liver (HepG2) cell line. HepG2 cells
      acted upon the prodrug to release NO, as assessed by nitrite levels, in a dose-
      and time-dependent fashion to maximal levels of 57-fold above control levels. In
      cells pretreated with V-PROLI/NO (200 microM, 24 h) then exposed to arsenic for
      an additional 24 h, arsenic was much less toxic (LC(50) = 151.9 +/- 5.9 microM)
      than in control cells (LC(50) = 90.5 +/- 6.5 microM) and the reduced
      cytolethality was directly related to the level of NO produced. V-PROLI/NO also
      increased CYP2E1 transcriptional expression in a dose-dependent manner and CYP2E1
      expression was directly related to the level of NO produced and the reduction in
      arsenic cytotoxicity. V-PROLI/NO pretreatment markedly reduced arsenic-induced
      apoptosis as measured by DNA fragmentation. Pretreatment with V-PROLI/NO
      suppressed phosphorylation of JNK1/2 after arsenic exposure. Arsenic increased
      metallothionein, a metal-binding protein important in arsenic tolerance, and V
      PROLI/NO pretreatment caused additional increases in metallothionein levels.
      Thus, the prodrug, V-PROLI/NO, protects against arsenic toxicity in cultured
      human liver cells, reducing cytolethality, apoptosis and dysregulation of mitogen
      activated protein kinases, through generation of NO formed after metabolism by
      liver cell enzymes, possibly including CYP2E1.

PMID- 19154404
TI  - Combination chemotherapy of oxaliplatin and 5-fluorouracil may be an effective
      regimen for mucinous adenocarcinoma of the ovary: a potential treatment strategy.
AB  - Resistance of ovarian mucinous adenocarcinoma to standard chemotherapy with
      paclitaxel and carboplatin is associated with poor prognosis, and an effective
      treatment is needed. The present study aimed to identify an effective
      chemotherapy for ovarian mucinous adenocarcinoma. Five human ovarian mucinous
      adenocarcinoma cell lines (MN-1, OMC-1, RMUG-L, RMUG-S, TU-OM-1) were used in
      this study. Sensitivity of the cells to the anticancer agents was determined by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and we assessed
      drug sensitivity by calculating the assay area under the curve for each agent.
      Protein expression was confirmed by Western blot analysis. We also examined the
      efficacy of combination chemotherapy on survival in a xenograft model of nude
      mice. The IC(50) to anticancer agents ranged widely. The assay area under the
      curve indicated that two of five cell lines (MN-1, TU-OM-1) were sensitive to
      oxaliplatin, 5-fluorouracil and etoposide, and only one (TU-OM-1) was sensitive
      to 7-ethyl-10-hydroxycamptothecin, which is an active metabolite of camptothecin.
      All cell lines were resistant to cisplatin and paclitaxel. The combination of
      oxaliplatin and 5-fluorouracil resulted in additive or synergistic effects on all
      cell lines. The combination of oxaliplatin and 5-fluorouracil significantly
      prolonged survival in a ovarian mucinous adenocarcinoma xenograft model of nude
      mice. Protein expression levels of the excision repair cross-complementation
      group 1 were lower in oxaliplatin sensitive cell lines. Exposure to 5
      fluorouracil down-regulated cross-complementation group 1 expression in ovarian
      mucinous adenocarcinoma cells. We conclude that combination chemotherapy
      consisting of oxaliplatin and 5-fluorouracil was an effective treatment for
      ovarian mucinous adenocarcinoma and may be a pivotal candidate for a novel
      treatment strategy.

PMID- 19154405
TI  - Chemokine CCL2 facilitates ICAM-1-mediated interactions of cancer cells and
      lymphatic endothelial cells in sentinel lymph nodes.
AB  - We examined the effects of CCL1, CCL2, CCL12 and CCL21 on the expression of
      adhesion molecules in cultured human lymphatic endothelial cells using
      immunohistochemical staining or Western blot analysis. In addition, we
      investigated whether the expressed adhesion molecule was able to facilitate the
      attachment of carcinoma cells to the lymphatic endothelial cells as an in vitro
      micrometastatic model. CCL2 caused a selective and significant expression of ICAM
      1 on human lymphatic endothelial cells but CCL1, CCL12 and CCL21 did not. By
      increasing the stimulation time from 4 to 18 and 48 h, the intensity of
      immunoreactivity for ICAM-1 was significantly increased in a time-dependent
      manner up to 18 h. The ICAM-1 mRNA levels were also elevated significantly up to
      18 h. The CCL2-mediated immunohistochemical expression of ICAM-1 was dose
      dependently increased from 10 pg/mL to 1 ng/mL. The CCL2-mediated expression of
      ICAM-1 was significantly reduced by neutralization of CCL2 using a specific CCL2
      antibody. The 18-h treatment with CCL2 caused a significant facilitation of in
      vitro attachment of MDA-MB-231 and MCF-7 cells to the lymphatic endothelial cells
      (LECs). The CCL2-mediated response in the attachment assay was also significantly
      reduced either by the neutralization of CCL2 or by additional treatment with anti
      ICAM-1 antibody. Immunohistochemical expression of ICAM-1, but not E-selectin,
      was strongly observed around and within the metastatic region of sentinel lymph
      node isolated from breast cancer patients. These findings suggest that CCL2
      induces selective and significant expression of ICAM-1 on cultured human
      lymphatic endothelial cells and then facilitates the attachment of carcinoma
      cells to the lymphatic endothelial cells, thus providing an in vitro
      micrometastatic model via the overexpression of ICAM-1.

PMID- 19154406
TI  - Large-scale quantitative clinical proteomics by label-free liquid chromatography
      and mass spectrometry.
AB  - We previously reported the development of an integrated proteome platform, namely
      2-Dimensional Image Converted Analysis of Liquid chromatography and mass
      spectrometry (2DICAL), for quantitative comparison of large peptide datasets
      generated by nano-flow liquid chromatography (LC) and mass spectrometry (MS). The
      key technology of 2DICAL was the precise adjustment of the retention time of LC
      by dynamic programming. In order to apply 2DICAL to clinical studies that require
      comparison of a large number of patient samples we further refined the
      calculation algorithm and increased the accuracy and speed of the peptide peak
      alignment using a greedy algorithm, which had been used for fast DNA sequence
      alignment. The peptide peaks of each sample with the same m/z were extracted
      every 1 m/z and displayed with along the horizontal axis. Here we report a
      precise comparison of more than 150,000 typtic peptide ion peaks derived from 70
      serum samples (40 patients with uterine endometrial cancer and 30 controls). The
      levels of 49 MS peaks were found to differ significantly between cancer patients
      and controls (P < 0.01, Welch's t-test and interquartile range [IQR] of >40), and
      the differential expression and identification of selected three proteins was
      validated by immunoblotting. 2DICAL was is highly advantageous for large-scale
      clinical proteomics because of its simple procedure, high throughput, and
      quantification accuracy.

PMID- 19154407
TI  - Alternative lengthening of telomeres frequently occurs in mismatch repair system
      deficient gastric carcinoma.
AB  - Maintenance of telomeric ends by the telomerase ribonucleoprotein complex or the
      telomerase-independent alternative lengthening of telomeres is necessary for the
      immortalization of human cells. The significance of alternative lengthening of
      telomeres has been suggested in DNA mismatch repair system-deficient cells;
      however, much remains unknown in human malignancies. In this study, we
      investigated the telomere maintenance mechanism in gastric carcinoma. In formalin
      fixed and paraffin-embedded sections of the high frequency of microsatellite
      instability (MSI-H) and non-MSI-H gastric carcinomas, there was no difference in
      telomere length monitored by telomere intensity ratio using telomere-fluorescent
      in situ hybridization. Immunoreactivity of hTERT, the catalytic subunit of
      telomerase, was detected in 48% of MSI-H gastric carcinomas. The frequency was
      significantly lower than that in non-MSI-H gastric carcinomas (86%, P = 0.02).
      Conversely, the number of the alternative lengthening of telomeres-associated
      promyelocytic leukemia bodies (APBs) detected by combined promyelocytic leukemia
      immunofluorescence and telomere-fluorescent in situ hybridization was
      statistically higher (57%) in the MSI-H gastric carcinomas compared to that in
      non-MSI-H gastric carcinomas (19%, P = 0.026). The cases with hTERT(+)APBs(-)
      were more frequent in non-MSI-H gastric carcinomas (76%) than in MSI-H gastric
      carcinomas (24%), and the cases with hTERT(-)APBs(+) were more frequent in MSI-H
      gastric carcinomas (33%) than in non-MSI-H gastric carcinomas (10%). These
      results suggest that alternative lengthening of telomeres-mediated telomere
      maintenance plays an important role for microsatellite instability-mediated
      stomach carcinogenesis, as well as the telomerase ribonucleoprotein complex,
      although the incidence of MSI-H is low. Defects of the mismatch repair system may
      lead to homeologous recombination of telomeric ends for the telomerase
      independent telomere maintenance in gastric carcinomas.

PMID- 19154408
TI  - Molecular imaging of cancer: evaluating characters of individual cancer by
      PET/SPECT imaging.
AB  - The present status of cancer molecular imaging (MI) with nuclear medicine
      techniques is reviewed, highlighting the Japanese activities in this field. With
      the progress in MI research, including significant contributions from Japanese
      studies, it has become possible to noninvasively evaluate various important
      characters of cancer in clinical patients, such as metabolism, cellular
      proliferation, tumor hypoxia, and receptor expression. Tumor metabolic
      information is used for tumor characterization, treatment response evaluation,
      and prognosis prediction. Hypoxia imaging is used for treatment planning and
      predicting treatment response. Receptor imaging can be used for the selection of
      the candidate for receptor-targeted treatment. Various novel probes that can
      target cancer-associated antigens, various cellular growth factor receptors,
      tumor angiogenesis, and so on, are under development, aiming for clinical
      evaluation. Application of radiolabeled ligands for treatment (targeted internal
      radiation therapy) is another important field in which MI technique can play a
      critical role. MI, which can deliver the outcome of basic oncological research to
      the bedside, is essential translational research for improved individualized
      patient management, and further advances in MI studies are eagerly awaited.

PMID- 19154409
TI  - Essential contribution of Ets-1 to constitutive Pim-3 expression in human
      pancreatic cancer cells.
AB  - We previously demonstrated that the proto-oncogene Pim-3 with serine/threonine
      kinase activity was aberrantly expressed in cancer cells but not in the normal
      cells of the pancreas. In order to elucidate the molecular mechanism underlying
      aberrant Pim-3 expression in pancreatic cancer cells, we constructed luciferase
      expression vectors linked to 5'-flanking deletion mutants of the human Pim-3 gene
      and transfected human pancreatic cancer cells with the resultant vectors. The
      region up to -264 bp was essential for constitutive Pim-3 gene expression, and
      the mutation in the Ets-1 binding site (between -216 and -211 bp) reduced
      luciferase activities. Moreover, Ets-1 mRNA and protein were constitutively
      expressed together with Pim-3 in human pancreatic cancer cell lines. Chromatin
      immunoprecipitation assay demonstrated constitutive binding of Ets-1 to the 5'
      flanking region of human Pim-3 gene between -249 and -183 bp. Pim-3 promoter
      activity and its protein expression were induced by transfection with wild type
      Ets-1 and were reduced by transfection with dominant negative-Ets-1 or Ets-1
      small-interfering RNA (siRNA). Furthermore, dominant negative-Ets-1 and Ets-1
      siRNA reduced the amount of Bad phosphorylated at its Ser(112) and induced
      apoptosis, when they were transfected into human pancreatic cancer cells.
      Finally, Pim-3 cDNA transfection reversed Ets-1 siRNA-induced increase in
      apoptosis and decrease in Bad phosphorylation at its Ser(112). These observations
      would indicate that the transcription factor Ets-1 can induce aberrant Pim-3
      expression and subsequently prevent apoptosis in human pancreatic cancer cells.

PMID- 19154410
TI  - Identification of C2orf18, termed ANT2BP (ANT2-binding protein), as one of the
      key molecules involved in pancreatic carcinogenesis.
AB  - Pancreatic ductal adenocarcinoma (PDAC) shows one of the worst mortality rates
      among the common malignancies, and the great majority of PDAC patients are
      diagnosed at an advanced stage where no effective therapy is presently available.
      Hence, identification of novel molecular targets and development of molecular
      therapy for PDAC are urgently required. Through our genome-wide gene expression
      profiles of microdissected PDAC cells, we here identified a novel gene C2orf18 as
      a molecular target for PDAC treatment. Transcriptional and immunohistochemical
      analysis validated its overexpression in PDAC cells and limited expression in
      normal adult organs. Knockdown of C2orf18 by small-interfering RNA in PDAC cell
      lines resulted in induction of apoptosis and suppression of cancer cell growth,
      suggesting its essential role in maintaining viability of PDAC cells. We showed
      that C2orf18 was localized in the mitochondria and it could interact with adenine
      nucleotide translocase 2 (ANT2), which is involved in maintenance of the
      mitochondrial membrane potential and energy homeostasis, and was indicated some
      roles in apoptosis. These findings implicated that C2orf18, termed ANT2-binding
      protein (ANT2BP), might serve as a candidate molecular target for pancreatic
      cancer therapy.

PMID- 19154411
TI  - Formosanin C-induced apoptosis requires activation of caspase-2 and change of
      mitochondrial membrane potential.
AB  - Formosanin C is a pure compound isolated from Paris formosana Hayata (Liliaceae).
      The antitumor efficacy of formosanin C has been observed in cultured cells and
      animal systems. However, the molecular mechanisms of formosanin C remain unknown.
      The results of the present study indicate that formosanin C induced apoptosis of
      HT-29 cells characterized by exposure of phosphatidylserine, accumulation of
      cells at the sub-G(1) phase, fragmentation of DNA, and change of nuclear
      morphology in a time- and dose-related manner. The apoptotic signaling cascades
      may proceed via proteolytic activation of caspase-2, change of mitochondrial
      membrane potential (Deltapsi(m)), release of cytochrome c and second mitochondria
      derived activator of caspase/direct IAP binding protein with low pI
      (Smac/DIABLO), activation of caspase-9 and -3, and cleavage of poly(ADP-ribose)
      polymerase (PARP). Increase in apoptosis-inducing factor and endonuclease G
      expressions in nuclei, and increase in Bax and Bak expressions and decrease in
      Bcl-X(L) expression on mitochondria were also observed in formosanin C-treated HT
      29 cells. Attenuation of formosanin C-induced change of Deltapsi(m) by caspase-2
      inhibitor (Z-VDVAC) implies that caspase-2 acts upstream of the mitochondria.
      Blockage of formosanin C-induced apoptotic process by using either permeability
      transition pore inhibitor (cyclosporine A) or caspase-9 inhibitor (Z-LEHD)
      demonstrates the necessity of mitochondria and caspase-9 in formosanin C-induced
      apoptosis of HT-29 cells. Taken together, the apoptotic mechanism of formosanin C
      in human colorectal cancer HT-29 cells involves activation of caspase-2 and the
      dysfunction of mitochondria.

PMID- 19154412
TI  - Impaired Tax-specific T-cell responses with insufficient control of HTLV-1 in a
      subgroup of individuals at asymptomatic and smoldering stages.
AB  - Human T-cell leukemia virus type-1 (HTLV-1)-specific T-cell immunity, a potential
      antitumor surveillance system in vivo, is impaired in adult T-cell leukemia
      (ATL). In this study, we aimed to clarify whether the T-cell insufficiency in ATL
      is present before the disease onset or occurs as a consequence of the disease. We
      investigated T-cell responses against Tax protein in peripheral blood mononuclear
      cells (PBMCs) from individuals at earlier stages of HTLV-1-infection, including
      21 asymptomatic HTLV-1 carriers (ACs) and four patients with smoldering-type ATL
      (sATL), whose peripheral lymphocyte count was in normal range. About 30% of
      samples tested showed clear Tax-specific interferon (IFN)-gamma producing
      responses. Proviral loads in this group were significantly lower than those in
      the other less-specific response group. The latter group was further divided to
      two subgroups with or without emergence of Tax-specific responses following
      depletion of CC chemokine receptor 4 (CCR4)(+) cells that contained HTLV-1
      infected cells. In the PBMCs with Tax-specific responses, CD8(+) cells
      efficiently suppressed HTLV-1 p19 production in culture. The remaining group
      without the emergence of Tax-specific response after CCR4(+) cell-depletion
      included at least two sATL and one AC samples, which spontaneously produced HTLV
      1 p19 in culture, where tetramer-binding, Tax-specific cytotoxic T-lymphocytes
      were either undetectable or unresponsive. Our results indicated that HTLV-1
      specific T-cell responsiveness widely differed among HTLV-1 carriers, and that
      impairment of HTLV-1-specific T-cell responses was observed not only in advanced
      ATL patients but also in a subpopulation at earlier stages, which was associated
      with insufficient control of HTLV-1.

PMID- 19154413
TI  - Leptin induces functional activation of cyclooxygenase-2 through JAK2/STAT3,
      MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells.
AB  - Hyperleptinemia is a common feature of obese women who have a higher risk of
      endometrial cancer than women with normal weights, and epidemiologic studies have
      suggested a correlation between obesity and endometrial carcinoma. Therefore,
      understanding of the molecular mechanism involved in leptin signaling
      transduction is important in endometrial cancer prevention and treatment. In this
      study, both isoforms of the leptin receptor (Ob-R), the long form (Ob-Rb) and
      short form (Ob-Ra), were detected as being expressed in six endometrial cancer
      cell lines with various differentiation status by western blotting, and Ob-Ra was
      found to be more abundant than Ob-Rb in these cells. Moreover, the expressions of
      both isoforms were inversely correlated with histoprognostic grading. We also
      showed that leptin stimulated cell proliferation and induced activations of
      signal transducers and activators of transcription 3 (STAT3), extracellular
      signal-regulated kinase (ERK1/2), AKT, and cyclooxygenase (COX)-2 in endometrial
      cancer cells dose-dependently by [(3)H] thymidine incorporation assay and western
      blotting. Leptin-stimulation resulted in increased expression of COX-2 mRNA and
      prostaglandin E2 (PGE2) production of endometrial cancer cells by reverse
      transcription-polymerase chain reaction and enzyme immunoassay, respectively,
      which was effectively blocked by pharmacological inhibitors of Janus tyrosine
      kinase 2 (JAK2), AG490; of mitogen-activated protein kinase (MAPK) kinase, U0126;
      of phosphatidylinositol 3-kinase (PI3K), LY294002; and of COX-2, NS398. These
      results suggest that leptin promotes cell proliferation of endometrial cancer
      cells via the aforementioned multiple signal-transduction pathways. Leptin
      induced functional activation of COX-2 is JAK2/STAT3-, MAPK/ERK-, and PI3K/AKT
      dependent, indicating that COX-2 may be a critical factor of endometrial
      carcinogenesis in obesity.

PMID- 19154414
TI  - Prevention of proliferative changes of forestomach mucosa by blood glucose
      control with insulin in alloxan-induced diabetic rats.
AB  - Diabetes mellitus is one of the risk factors for carcinogenesis. Recently we
      reported that alloxan induces squamous cell carcinoma (SCC) with coincidental
      inflammation, bacteria/fungal infections, and a severe diabetic condition. The
      present study was conducted to examine the effects of blood glucose control with
      insulin on the proliferative changes of the forestomach in alloxan-induced
      diabetic rats. Male 15-week-old WBN/Kob rats were divided into a control group of
      non-treated rats with naturally occurring diabetes after 40 weeks of age (non
      treated group), alloxan-induced diabetic rats (AL group), and alloxan-induced
      diabetic rats given insulin implant treatment (AL + In group). The animals were
      sacrificed at 90 weeks of age for histopathologic examination. The blood glucose
      and urinary glucose level of the AL + In group fluctuated variously from high to
      normal levels compared with a constantly high level of AL (for 75 weeks) as well
      as in the non-treated group (for 50 weeks). The mucosal hyperplasia in the
      forestomach developed in 88.2% of the AL group and 37.5% of the non-treated
      group, but in only 10.0% of the AL + In group. SCC was only detected in 23.5% of
      the AL group. Hyperplastic changes were constantly accompanied by inflammation
      and fungal/bacterial infections in the AL and non-treated groups, whereas
      inflammation and fungal infection were completely suppressed in the AL + In
      group. These findings demonstrate that blood glucose control suppressed
      neoplastic changes in alloxan-induced diabetic rats. We postulate that
      inflammation together with bacterial/fungal infections under prolonged severe
      diabetic conditions play a pivotal role in carcinogenesis.

PMID- 19154415
TI  - Overexpression of protease inhibitor-dead secretory leukocyte protease inhibitor
      causes more aggressive ovarian cancer in vitro and in vivo.
AB  - The alarm anti-protease secretory leukocyte protease inhibitor (SLPI) is
      frequently overexpressed in ovarian cancer cells and has been proposed for
      inclusion in biomarker panels but function remains unclear. We hypothesized that
      SLPI overexpression promotes ovarian cancer growth and survival. Low SLPI
      expressing Hey-A8 ovarian cancer cells were engineered to produce functional (WT)
      or protease inhibitor-null (PI-) mutant SLPI; lack of PI activity was confirmed
      by enzymatic assay. WT/SLPI and PI- mutants stimulated significant proliferation
      and survival of Hey-A8 ovarian cancer cells under basal culture conditions (P <
      or = 0.02), in soft agar colony number and size (P < or = 0.05), and in anoikis
      resistance (P < or = 0.005). SLPI protected the ovarian cancer survival factor,
      progranulin (PRGN), and HEY-A8 cells from degradation and apoptosis due to
      neutrophil elastase. PI-/SLPI cells had greater protective activity than WT/SLPI
      cells. HEY-A8 murine xenografts revealed enhanced solid tumor formation,
      dissemination, and invasion in WT/SLPI and PI-/SLPI mutants. Increased
      proliferation was demonstrated by Ki-67 staining (P < or = 0.02). Increased
      secreted PRGN was seen in culture and was also observed by immunohistochemistry
      in the SLPI transfectant xenografts. This study describes a PI-independent
      function for SLPI in ovarian cancer growth and dissemination.

PMID- 19154416
TI  - Inhibition of heat shock protein 90 sensitizes melanoma cells to thermosensitive
      ferromagnetic particle-mediated hyperthermia with low Curie temperature.
AB  - Heat shock protein (Hsp) 90 is a key regulator of a variety of oncogene products
      and cell-signaling molecules, and the therapeutic benefit of its inhibition in
      combination with radiation or chemotherapy has been investigated. In addition,
      hyperthermia has been used for many years to treat various malignant tumors. We
      previously described a system in which hyperthermia was induced using
      thermosensitive ferromagnetic particles (FMP) with a Curie temperature (Tc = 43
      degrees C) low enough to mediate automatic temperature control, and demonstrated
      its antitumor effect in a mouse melanoma model. In the present study, we examined
      the antitumor effects of combining a Hsp90 inhibitor (geldanamycin; GA) with FMP
      mediated hyperthermia. In cultured B16 melanoma cells, GA exerted an antitumor
      effect by increasing the cells' susceptibility to hyperthermia and reducing
      expression of Akt. In an in vivo study, melanoma cells were subcutaneously
      injected into the backs of C57BL/6 mice. FMP were then injected into the
      resultant tumors, and the mice were divided into four groups: group I, no
      treatment (control); group II, one hyperthermia treatment; group III, GA alone;
      and group IV, GA with hyperthermia. When exposed to a magnetic field, the
      temperature of tissues containing FMP increased and stabilized at the Tc. In
      group IV, complete regression of tumors was observed in five of nine mice (56%),
      whereas no tumor regression was seen in groups I-III. Our findings suggest that
      inhibition of Hsp90 with hyperthermia increases its antitumor effect. Thus, the
      combination of FMP-mediated, self-regulating hyperthermia with Hsp90 inhibition
      has important implications for the treatment of cancer.

PMID- 19154417
TI  - Epidermal growth factor receptor lacking C-terminal autophosphorylation sites
      retains signal transduction and high sensitivity to epidermal growth factor
      receptor tyrosine kinase inhibitor.
AB  - Constitutively active mutations of epidermal growth factor receptor (EGFR)
      (delE746_A750) activate downstream signals, such as ERK and Akt, through the
      phosphorylation of tyrosine residues in the C-terminal region of EGFR. These
      pathways are thought to be important for cellular sensitivity to EGFR tyrosine
      kinase inhibitors (TKI). To examine the correlation between phosphorylation of
      the tyrosine residues in the C-terminal region of EGFR and cellular sensitivity
      to EGFR TKI, we used wild-type (wt) EGFR, as well as the following constructs:
      delE746_A750 EGFR; delE746_A750 EGFR with substitution of seven tyrosine residues
      to phenylalanine in the C-terminal region; and delE746_A750 EGFR with a C
      terminal truncation at amino acid 980. These constructs were transfected stably
      into HEK293 cells and designated HEK293/Wt, HEK293/D, HEK293/D7F, and HEK293/D
      Tr, respectively. The HEK293/D cells were found to be 100-fold more sensitive to
      EGFR TKI (AG1478) than HEK293/Wt. Surprisingly, the HEK293/D7F and HEK293/D-Tr
      cells, transfected with EGFR lacking the C-terminal autophosphorylation sites,
      retained high sensitivity to EGFR TKI. In these three high-sensitivity cells, the
      ERK pathway was activated without ligand stimulation, which was inhibited by EGFR
      TKI. In addition, although EGFR in the HEK293/D7F and HEK293/D-Tr cells lacked
      significant tyrosine residues for EGFR signal transduction, phosphorylation of
      Src homology and collagen homology (Shc) was spontaneously activated in these
      cells. Our results indicate that tyrosine residues in the C-terminal region of
      EGFR are not required for cellular sensitivity to EGFR TKI, and that an as-yet
      unknown signaling pathway of EGFR may exist that is independent of the C-terminal
      region of EGFR.

PMID- 19154418
TI  - Chicken ovalbumin upstream promoter transcription factor II in human breast
      carcinoma: possible regulator of lymphangiogenesis via vascular endothelial
      growth factor-C expression.
AB  - Chicken ovalbumin upstream promoter transcription factors (COUP-TF) are orphan
      members of the nuclear receptor superfamily and consist of COUP-TFI and COUP
      TFII. COUP-TFI was reported to be overexpressed in human breast cancer and to
      promote estrogen-independent transcriptional activity of estrogen receptor alpha.
      COUP-TFII, however, has not been examined in the breast. Therefore, we carried
      out immunohistochemical analysis of COUP-TFII in human breast cancer in order to
      clarify its biological and clinical significance. We immunolocalized COUP-TFII in
      119 human breast cancers and correlated the findings with various
      clinicopathological parameters. Fifty-nine percent of the cases were
      immunohistochemically positive for COUP-TFII. COUP-TFII positivity was correlated
      with poor clinical outcome, and a statistically significant correlation was
      detected between COUP-TFII and the following clinicopathological parameters:
      clinical stage, lymph node status, histological grade, and estrogen receptor
      alpha status. In addition, short interfering RNA-mediated knockdown of COUP-TFII
      in the breast carcinoma cell line MCF-7 decreased the level of vascular
      endothelial growth factor-C mRNA expression, which is a known inducer of
      lymphangiogenesis and lymph node metastasis. These results suggest that COUP-TFII
      is involved in the development of advanced human breast cancer.

PMID- 19154419
TI  - Is laparoscopic surgery acceptable for advanced colon cancer?
AB  - Laparoscopic surgery is widespread in the treatment of colorectal cancer. In
      Japan, a nationwide survey has shown that the rate of advanced colorectal cancer
      has increased gradually to 65% of total laparoscopic surgeries in 2007. Many
      randomized controlled trials have demonstrated that in the short term,
      laparoscopic surgery is feasible, safe, and has many benefits, including
      reduction of peri-operative mortality. In terms of long-term outcomes, four
      randomized controlled trials suggest that there are no differences in laparosupic
      and open surgery for colon cancer. However, important issues, including long-term
      oncological outcome, cost effectiveness, and the impact on the quality of life of
      patients, should be addressed in well-designed large-scale trials. In Japan, a
      retrospective multicenter study has demonstrated that the short-term outcomes of
      laparoscopic surgery are beneficial, and the long-term outcomes are the same as
      for open surgery. In 2004, a prospective large-scale randomized controlled trial
      (JCOG0404) to compare laparoscopic surgery with open surgery was started to
      evaluate oncological outcomes for advanced colon cancer. This trial is supported
      in part by a Grant-in-Aid for Cancer Research from the Japanese Ministry of
      Health, Labour, and Welfare. In the present study, laparoscopic surgery is found
      to be acceptable for stage I disease of colon cancer, whereas it is controversial
      for stage II/III disease because of inadequate clinical evidence. Whether
      laparoscopic surgery is acceptable for advanced colon cancer or not should be
      confirmed by the Japanese large-scale prospective randomized controlled trial
      (JCOG0404) in the near future.

PMID- 19154420
TI  - The impact of cytokines on the expression of drug transporters, cytochrome P450
      enzymes and chemokine receptors in human PBMC.
AB  - BACKGROUND AND PURPOSE: The function of transporters in peripheral blood
      mononuclear cells (PBMC) has been characterized, but less is known about
      cytochrome P450 (CYP) enzyme function in these cells. Given that cytokines are
      dysregulated in many diseases, the purpose of this work was to assess the impact
      of cytokines on the expression of CYPs, transporters and chemokine receptors in
      PBMC. EXPERIMENTAL APPROACH: Human PBMC were incubated with cytokines for 48 h.
      ATP-binding cassette (ABC)B1, ABCC1, ABCC2, CYP2B6, CYP3A4, CXCR4 and CCR5
      expression were measured by quantitative polymerase chain reaction and flow
      cytometry at 0, 4, 8, 24 and 48 h. Enzyme activity was assessed using fluorescent
      probes. KEY RESULTS: We show here functional activity of CYP3A4 and CYP2B6 in
      PBMC. Furthermore, cytokines had a significant impact on the mRNA and protein
      expression of all proteins. For example, interleukin-2 (IL-2) had a marked impact
      on ABCB1 mRNA (% control 4745 +/- 11961) and protein (% control 200 +/- 57).
      Increases in drug efflux transporter expression, in response to cytokines,
      resulted in reduced cellular accumulation of digoxin [decrease of 17% and 26% for
      IL-2 and interferon-gamma (IFNgamma) respectively] and saquinavir (decrease of
      28% and 30% for IL-2 and IFNgamma respectively). The degree to which drug
      transporter and chemokine receptor expression changed in response to cytokines
      was positively correlated (e.g. ABCB1 and CXCR4, r(2) = 0.545). CONCLUSIONS AND
      IMPLICATIONS: These data have important implications for diseases in which
      cytokines are dysregulated and for which pharmacological intervention targets
      immune cells.

PMID- 19154422
TI  - Pharmacological characterization of recombinant NR1/NR2A NMDA receptors with
      truncated and deleted carboxy termini expressed in Xenopus laevis oocytes.
AB  - BACKGROUND AND PURPOSE: The carboxy terminal domain (CTD) of NR2 N-methyl-d
      aspartate receptor (NMDAR) subunits interacts with numerous scaffolding and
      signal transduction proteins. Mutations of this region affect trafficking and
      downstream signalling of NMDARs. This study determines to what extent
      characteristic pharmacological properties of NR2A-containing NMDARs are
      influenced by this key functional domain. EXPERIMENTAL APPROACH: Using
      recombinant receptor expression in Xenopus laevis oocytes and two electrode
      voltage clamp recordings we characterized pharmacological properties of rat
      NR1/NR2A NMDARs with altered CTDs. We assessed the effects of truncating [at
      residue Iso1098; NR2A(trunC)] and deleting [from residue Phe822; NR2A(delC)] the
      CTD of NR2A NMDAR subunits on agonist potencies, channel block by Mg(2+) and
      memantine and potentiation of NMDAR-mediated responses by chelating contaminating
      divalent cations. KEY RESULTS: Truncation or deletion of the CTD of NR2A NMDAR
      subunits did not affect glutamate potency [EC(50) = 2.2 micromol.L(-1),
      NR2A(trunC); 2.7 micromol.L(-1), NR2A(delC) compared with 3.3 micromol.L(-1),
      NR2A(WT)] but did significantly increase glycine potency [EC(50) = 500 nmol.L(
      1), NR2A(trunC); 900 nmol.L(-1), NR2A(delC) compared with 1.3 micromol.L(-1),
      NR2A(WT)]. Voltage-dependent Mg(2+) block of NR2A(WT)- and NR2A(trunC)-containing
      NMDARs was similar but low concentrations of Mg(2+) (1 micromol.L(-1))
      potentiated NR1/NR2A(delC) NMDARs. Memantine block was not affected by changes to
      the structure of the NR2A CTD. EDTA-induced potentiation was similar at each of
      the three NMDAR constructs. CONCLUSIONS AND IMPLICATIONS: Of the parameters
      studied only minor influences of the CTD were observed; these are unlikely to
      compromise interpretation of studies that make use of CTD-mutated recombinant
      receptors or transgenic mice in investigations of the role of the CTD in NMDAR
      signalling.

PMID- 19154421
TI  - Physical methods of nucleic acid transfer: general concepts and applications.
AB  - Physical methods of gene (and/or drug) transfer need to combine two effects to
      deliver the therapeutic material into cells. The physical methods must induce
      reversible alterations in the plasma membrane to allow the direct passage of the
      molecules of interest into the cell cytosol. They must also bring the nucleic
      acids in contact with the permeabilized plasma membrane or facilitate access to
      the inside of the cell. These two effects can be achieved in one or more steps,
      depending upon the methods employed. In this review, we describe and compare
      several physical methods: biolistics, jet injection, hydrodynamic injection,
      ultrasound, magnetic field and electric pulse mediated gene transfer. We describe
      the physical mechanisms underlying these approaches and discuss the advantages
      and limitations of each approach as well as its potential application in research
      or in preclinical and clinical trials. We also provide conclusions, comparisons,
      and projections for future developments. While some of these methods are already
      in use in man, some are still under development or are used only within clinical
      trials for gene transfer. The possibilities offered by these methods are,
      however, not restricted to the transfer of genes and the complementary uses of
      these technologies are also discussed. As these methods of gene transfer may
      bypass some of the side effects linked to viral or biochemical approaches, they
      may find their place in specific clinical applications in the future.

PMID- 19154423
TI  - Accelerated inactivation of cardiac L-type calcium channels triggered by
      anaesthetic-induced preconditioning.
AB  - BACKGROUND AND PURPOSE: Cardioprotection against ischaemia by anaesthetic-induced
      preconditioning (APC) is well established. However, the mechanism underlying
      Ca(2+) overload attenuation by APC is unknown. The effects of APC by isoflurane
      on the cardiac L-type Ca channel were investigated. EXPERIMENTAL APPROACH: In a
      model of in vivo APC, Wistar rats were exposed to isoflurane (1.4%), delivered
      via a vaporizer in an enclosure, prior to thoracotomy. The Dahl S rats were
      similarly preconditioned to determine strain-dependent effects. Whole-cell patch
      clamp using cardiac ventricular myocytes was used to determine the L-type Ca(2+)
      current (I(Ca,L)) characteristics and calmodulin (CaM) levels were determined by
      Western blot analysis. Cytosolic Ca(2+) levels were monitored using fluo-4-AM.
      Action potential (AP) simulations examined the effects of APC. KEY RESULTS: In
      Wistar rats, APC significantly accelerated I(Ca,L) inactivation kinetics. This
      was abolished when external Ca(2+) was replaced with Ba(2+), suggesting that
      Ca(2+)-dependent inactivation of I(Ca,L) was modulated by APC. Expression levels
      of CaM, a determinant of I(Ca,L) inactivation, were not affected. Attenuation of
      cytosolic Ca(2+) accumulation following oxidative stress was observed in the APC
      group. Simulations showed that the accelerated inactivation of I(Ca,L) resulted
      in a shortening of the AP duration. The Dahl S rat strain was resistant to APC
      and changes in I(Ca,L) inactivation were not observed in cardiomyocytes prepared
      from these rats. CONCLUSIONS AND IMPLICATIONS: APC triggered persistent changes
      in the inactivation of cardiac L-type Ca channels. This can potentially lead to a
      reduction in Ca(2+) influx and attenuation of Ca(2+) overload during
      ischaemia/reperfusion.

PMID- 19154424
TI  - Levosimendan induces NO production through p38 MAPK, ERK and Akt in porcine
      coronary endothelial cells: role for mitochondrial K(ATP) channel.
AB  - BACKGROUND AND PURPOSE: Levosimendan acts as a vasodilator through the opening of
      ATP-sensitive K(+) channels (K(ATP)) channels. Moreover, the coronary
      vasodilatation caused by levosimendan in anaesthetized pigs has recently been
      found to be abolished by the nitric oxide synthase (NOS) inhibitor N(omega)-nitro
      L-arginine methyl ester, indicating that nitric oxide (NO) has a role in the
      vascular effects of levosimendan. However, the intracellular pathway leading to
      NO production caused by levosimendan has not yet been investigated. Thus, the
      purpose of the present study was to examine the effects of levosimendan on NO
      production and to evaluate the intracellular signalling pathway involved.
      EXPERIMENTAL APPROACH: In porcine coronary endothelial cells (CEC), the release
      of NO in response to levosimendan was examined in the presence and absence of
      N(omega)-nitro-L-arginine methyl ester, an adenylyl cyclase inhibitor, K(ATP)
      channel agonists and antagonists, and inhibitors of intracellular protein
      kinases. In addition, the role of Akt, ERK, p38 and eNOS was investigated through
      Western blot analysis. KEY RESULTS: Levosimendan caused a concentration-dependent
      and K(+)-related increase of NO production. This effect was amplified by the
      mitochondrial K(ATP) channel agonist, but not by the selective plasma membrane
      K(ATP) channel agonist. The response of CEC to levosimendan was prevented by the
      K(ATP) channel blockers, the adenylyl cyclase inhibitor and the Akt, ERK, p38
      inhibitors. Western blot analysis showed that phosphorylation of the above
      kinases lead to eNOS activation. CONCLUSIONS AND IMPLICATIONS: In CEC
      levosimendan induced eNOS-dependent NO production through Akt, ERK and p38. This
      intracellular pathway is associated with the opening of mitochondrial K(ATP)
      channels and involves cAMP.

PMID- 19154425
TI  - P-selectin glycoprotein-ligand-1 regulates pulmonary recruitment of neutrophils
      in a platelet-independent manner in abdominal sepsis.
AB  - BACKGROUND AND PURPOSE: Neutrophil-mediated lung injury is an insidious feature
      in sepsis although the mechanisms regulating pulmonary recruitment of neutrophils
      remain elusive. Here, we investigated the role of P-selectin glycoprotein-ligand
      1 (PSGL-1) in sepsis-induced neutrophil recruitment and tissue injury in the
      lung. EXPERIMENTAL APPROACH: Bronchoalveolar infiltration of neutrophils, levels
      of myeloperoxidase, oedema formation and CXC chemokines were determined 24 h
      after caecal ligation and puncture (CLP) in mice. Animals were pretreated with a
      control antibody, monoclonal antibodies directed against PSGL-1 and P-selectin as
      well as a platelet-depleting antibody directed against GP1balpha. KEY RESULTS:
      CLP caused pulmonary damage characterized by oedema formation, neutrophil
      infiltration and increased levels of CXC chemokines in the lung.
      Immunoneutralization of PSGL-1 or P-selectin reduced CLP-induced neutrophil
      recruitment in the bronchoalveolar space by more than 56% and lung
      myeloperoxidase activity by 62%. Notably, the inhibitory effect of the anti-PSGL
      1 antibody on sepsis-induced neutrophil infiltration was also observed in
      platelet-depleted mice. Moreover, inhibition of PSGL-1 and P-selectin abolished
      CLP-induced oedema formation and tissue damage in the lung. CLP-induced formation
      of CXC chemokines was not changed in mice pretreated with the anti-PSGL-1 and
      anti-P-selectin antibodies. CONCLUSIONS AND IMPLICATIONS: These data demonstrate
      that PSGL-1 plays a key role in pulmonary infiltration of neutrophils as well as
      lung oedema associated with abdominal sepsis. Moreover, our findings suggest that
      PSGL-1-dependent neutrophil recruitment is independent of circulating platelets.
      Thus, these novel findings indicate that PSGL-1 may be a useful target to protect
      against sepsis-induced accumulation of neutrophils and tissue damage in the lung.

PMID- 19154426
TI  - Selective noradrenaline reuptake inhibitor atomoxetine directly blocks hERG
      currents.
AB  - BACKGROUND AND PURPOSE: Atomoxetine is a selective noradrenaline reuptake
      inhibitor, recently approved for the treatment of attention-deficit/hyperactivity
      disorder. So far, atomoxetine has been shown to be well tolerated, and
      cardiovascular effects were found to be negligible. However, two independent
      cases of QT interval prolongation, associated with atomoxetine overdose, have
      been reported recently. We therefore analysed acute and subacute effects of
      atomoxetine on cloned human Ether-a-Go-Go-Related Gene (hERG) channels.
      EXPERIMENTAL APPROACH: hERG channels were heterologously expressed in Xenopus
      oocytes and in a human embryonic kidney cell line and hERG currents were measured
      using voltage clamp and patch clamp techniques. Action potential recordings were
      made in isolated guinea-pig cardiomyocytes. Gene expression and channel surface
      expression were analysed using quantitative reverse transcriptase polymerase
      chain reaction, Western blot and the patch clamp techniques. KEY RESULTS: In
      human embryonic kidney cells, atomoxetine inhibited hERG current with an IC(50)
      of 6.3 micromol.L(-1). Development of block and washout were fast. Channel
      activation and inactivation were not affected. Inhibition was state-dependent,
      suggesting an open channel block. No use-dependence was observed. Inhibitory
      effects of atomoxetine were attenuated in the pore mutants Y652A and F656A. In
      guinea-pig cardiomyocytes, atomoxetine lengthened action potential duration
      without inducing action potential triangulation. Overnight incubation with high
      atomoxetine concentrations resulted in a decrease of channel surface expression.
      CONCLUSIONS AND IMPLICATIONS: Whereas subacute effects of atomoxetine seem
      negligible under therapeutically relevant concentrations, hERG channel block
      should be considered in cases of atomoxetine overdose and when administering
      atomoxetine to patients at increased risk for the development of acquired long-QT
      syndrome.

PMID- 19154427
TI  - Inhibitory actions of the phosphatidylinositol 3-kinase inhibitor LY294002 on the
      human Kv1.5 channel.
AB  - BACKGROUND AND PURPOSE: Kv1.5 channels conduct the ultra-rapid delayed rectifier
      potassium current (I(Kur)), and in humans, Kv1.5 channels are highly expressed in
      cardiac atria but are scarce in ventricles. Pharmacological blockade of human
      Kv1.5 (hKv1.5) has been regarded as effective for prevention and treatment of re
      entry-based atrial tachyarrhythmias. Here we examined blockade of hKv1.5 channels
      by LY294002, a well-known inhibitor of phosphatidylinositol 3-kinase (PI3K).
      EXPERIMENTAL APPROACH: hKv1.5 channels were heterologously expressed in Chinese
      hamster ovary cells. Effects of LY294002 on wild-type and mutant (T462C, H463C,
      T480A, R487V, A501V, I502A, I508A, L510A and V516A) hKv1.5 channels were examined
      by using the whole-cell patch-clamp method. KEY RESULTS: LY294002 rapidly and
      reversibly inhibited hKv1.5 current in a concentration-dependent manner (IC(50)
      of 7.9 micromol.L(-1)). In contrast, wortmannin, a structurally distinct
      inhibitor of PI3K, had little inhibitory effect on hKv1.5 current. LY294002 block
      of hKv1.5 current developed with time during depolarizing voltage-clamp steps,
      and this blockade was also voltage-dependent with a steep increase over the
      voltage range for channel openings. The apparent binding (k(+1)) and unbinding
      (k(-1)) rate constants were calculated to be 1.6 micromol.L(-1) (-1).s(-1) and
      5.7 s(-1) respectively. Inhibition by LY294002 was significantly reduced in
      several hKv1.5 mutant channels: T480A, R487V, I502A, I508A, L510A and V516A.
      CONCLUSIONS AND IMPLICATIONS: LY294002 acts directly on hKv1.5 currents as an
      open channel blocker, independently of its effects on PI3K activity. Amino acid
      residues located in the pore region (Thr480, Arg487) and the S6 segment (Ile502,
      Ile508, Leu510, Val516) appear to constitute potential binding sites for
      LY294002.

PMID- 19154428
TI  - Relative contribution of ecto-ATPase and ecto-ATPDase pathways to the biphasic
      effect of ATP on acetylcholine release from myenteric motoneurons.
AB  - BACKGROUND AND PURPOSE: The relative contribution of distinct ecto-nucleotidases
      to the modulation of purinergic signalling may depend on differential tissue
      distribution and substrate preference. EXPERIMENTAL APPROACH: Extracellular ATP
      catabolism (assessed by high-performance liquid chromatography) and its influence
      on [(3)H]acetylcholine ([(3)H]ACh) release were investigated in the myenteric
      plexus of rat ileum in vitro. KEY RESULTS: ATP was primarily metabolized via ecto
      ATPDase (adenosine 5'-triphosphate diphosphohydrolase) into AMP, which was then
      dephosphorylated into adenosine by ecto-5'-nucleotidase. Alternative conversion
      of ATP into ADP by ecto-ATPase (adenosine 5'-triphosphatase) was more relevant at
      high ATP concentrations. ATP transiently increased basal [(3)H]ACh outflow in a
      2',3'-O-(2,4,6-trinitrophenyl)adenosine-5'-triphosphate (TNP-ATP)-dependent,
      tetrodotoxin-independent manner. ATP and ATPgammaS (adenosine 5'-[gamma
      thio]triphosphate), but not alpha,beta-methyleneATP, decreased [(3)H]ACh release
      induced by electrical stimulation. ADP and ADPbetaS (adenosine 5'[beta
      thio]diphosphate) only decreased evoked [(3)H]ACh release. Inhibition by ADPbetaS
      was prevented by MRS 2179 (2'-deoxy-N(6)-methyl adenosine 3',5'-diphosphate
      diammonium salt, a selective P2Y(1) antagonist); blockade of ADP inhibition
      required co-application of MRS 2179 plus adenosine deaminase (which inactivates
      endogenous adenosine). Blockade of adenosine A(1) receptors with 1,3-dipropyl-8
      cyclopentyl xanthine enhanced ADPbetaS inhibition, indicating that P2Y(1)
      stimulation is cut short by tonic adenosine A(1) receptor activation. MRS 2179
      facilitated evoked [(3)H]ACh release, an effect reversed by the ecto-ATPase
      inhibitor, ARL67156, which delayed ATP conversion into ADP without affecting
      adenosine levels. CONCLUSIONS AND IMPLICATIONS: ATP transiently facilitated
      [(3)H]ACh release from non-stimulated nerve terminals via prejunctional P2X
      (probably P2X(2)) receptors. Hydrolysis of ATP directly into AMP by ecto-ATPDase
      and subsequent formation of adenosine by ecto-5'-nucleotidase reduced [(3)H]ACh
      release via inhibitory adenosine A(1) receptors. Stimulation of inhibitory P2Y(1)
      receptors by ADP generated alternatively via ecto-ATPase might be relevant in
      restraining ACh exocytosis when ATP saturates ecto-ATPDase activity.

PMID- 19154429
TI  - Simvastatin protects against cholestasis-induced liver injury.
AB  - BACKGROUND: Bile duct obstruction is associated with hepatic accumulation of
      leukocytes and liver injury. The aim of this study was to evaluate the effect of
      simvastatin on cholestasis-induced liver inflammation and tissue damage.
      EXPERIMENTAL APPROACH: C57BL/6 mice were treated with simvastatin (0.02 and 0.2
      mg.kg(-1)) and vehicle before and after undergoing bile duct ligation (BDL) for
      12 h. Leukocyte recruitment and microvascular perfusion in the liver were
      analysed using intravital fluorescence microscopy. CXC chemokines in the liver
      were determined by enzyme-linked immunosorbent assay. Liver damage was monitored
      by measuring serum levels of alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST). Hepatic levels of myeloperoxidase (MPO) were also
      determined. KEY RESULTS: Administration of 0.2 mg.kg(-1) simvastatin decreased
      ALT and AST by 87% and 83%, respectively, in BDL mice. This dose of simvastatin
      reduced hepatic formation of CXC chemokines by 37-82% and restored sinusoidal
      perfusion in cholestatic animals. Moreover, BDL-induced leukocyte adhesion in
      sinusoids and postsinusoidal venules, as well as MPO levels in the liver, was
      significantly reduced by simvastatin. Notably, administration of 0.2 mg.kg(-1)
      simvastatin 2 h after BDL induction also decreased cholestatic liver injury and
      inflammation. CONCLUSIONS AND IMPLICATIONS: These findings show that simvastatin
      protects against BDL-induced liver injury. The hepatoprotective effect of
      simvastatin is mediated, at least in part, by reduced formation of CXC chemokines
      and leukocyte recruitment. Thus, our novel data suggest that the use of statins
      may be an effective strategy to protect against the hepatic injury associated
      with obstructive jaundice.

PMID- 19154430
TI  - Pharmacokinetic optimization of four soluble epoxide hydrolase inhibitors for use
      in a murine model of inflammation.
AB  - BACKGROUND AND PURPOSE: Early soluble epoxide hydrolase inhibitors (sEHIs) such
      as 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) are effective anti
      hypertensive and anti-inflammatory agents in various animal models. However,
      their poor metabolic stability and limited water solubility make them difficult
      to use pharmacologically. Here we present the evaluation of four sEHIs for
      improved pharmacokinetic properties and the anti-inflammatory effects of one
      sEHI. EXPERIMENTAL APPROACH: The pharmacokinetic profiles of inhibitors were
      determined following p.o. (oral) administration and serial bleeding in mice.
      Subsequently the pharmacokinetics of trans-4-[4-(3-adamantan-1-yl-ureido)
      cyclohexyloxy]-benzoic acid (t-AUCB), the most promising inhibitor, was further
      studied following s.c. (subcutaneous), i.v. (intravenous) injections and
      administration in drinking water. Finally, the anti-inflammatory effect of t-AUCB
      was evaluated by using a lipopolysaccharide (LPS)-treated murine model. KEY
      RESULTS: Better pharmacokinetic parameters (higher C(max), longer t(1/2) and
      greater AUC) were obtained from the tested inhibitors, compared with AUDA. Oral
      bioavailability of t-AUCB (0.1 mg.kg(-1)) was 68 +/- 22% (n = 4), and giving t
      AUCB in drinking water is recommended as a feasible, effective and easy route of
      administration for chronic studies. Finally, t-AUCB (p.o.) reversed the decrease
      in plasma ratio of lipid epoxides to corresponding diols (a biomarker of soluble
      epoxide hydrolase inhibition) in lipopolysaccharide-treated mice. The in vivo
      potency of 1 mg.kg(-1) of t-AUCB (p.o.) was better in this inflammatory model
      than that of 10 mg.kg(-1) of AUDA-butyl ester (p.o) at 6 h after treatment.
      CONCLUSIONS AND IMPLICATIONS: t-AUCB is a potent sEHI with improved
      pharmacokinetic properties. This compound will be a useful tool for
      pharmacological research and a promising starting point for drug development.

PMID- 19154431
TI  - The effect of 'two hit' neonatal and young-adult stress on dopaminergic
      modulation of prepulse inhibition and dopamine receptor density.
AB  - BACKGROUND AND PURPOSE: A combination of early neurodevelopmental insult(s) and
      young-adult stress exposure may be involved in the development of schizophrenia.
      We studied prepulse inhibition (PPI) regulation in rats after an early stress,
      maternal deprivation, combined with a later stress, simulated by chronic
      corticosterone treatment, and also determined whether changes in brain dopamine
      receptor density were involved. EXPERIMENTAL APPROACH: Rats were subjected to
      either 24 h maternal deprivation on postnatal day 9, corticosterone treatment
      from 8 to 10 weeks of age, or both. At 12 weeks of age, the rats were injected
      with 0.1, 0.3 or 1.0 mg.kg(-1) of apomorphine or 0.5 or 2.5 mg.kg(-1) of
      amphetamine and PPI was determined using automated startle boxes. Dopamine D(1)
      and D(2) receptor levels were assessed in the nucleus accumbens and caudate
      nucleus using receptor autoradiography. KEY RESULTS: Young-adult treatment with
      corticosterone resulted in attenuated disruption of PPI by apomorphine and
      amphetamine. In some rats, maternal deprivation resulted in reduced baseline PPI
      which added to the effect of corticosterone treatment. There was no down
      regulation of dopamine D(1) or D(2) receptors. CONCLUSIONS AND IMPLICATIONS:
      These results confirm and extend our finding of an inhibitory interaction of
      developmental stress on dopaminergic regulation of PPI. No corresponding changes
      in dopamine receptor density were observed in brain regions with a major
      involvement in PPI regulation, suggesting long-lasting desensitization of
      dopamine receptor signalling or indirect changes in PPI regulation.

PMID- 19154432
TI  - Selective desensitization of the 5-HT4 receptor-mediated response in pig atrium
      but not in stomach.
AB  - BACKGROUND AND PURPOSE: The time dependency of the effect of 5-HT(4) receptor
      agonists depends on many specific regulatory mechanisms, which vary between
      tissues. This has important implications with regard to the effects of endogenous
      5-HT, as well as to the clinical use of 5-HT(4) receptor agonists, and might
      contribute to tissue selectivity of agonists. EXPERIMENTAL APPROACH: The
      progression and desensitization of 5-HT(4) receptor-mediated responses were
      evaluated in an organ bath set-up using two, clinically relevant, porcine in
      vitro models: gastric cholinergic neurotransmission and atrial contractility. KEY
      RESULTS: Exposure of gastric tissue to 5-HT or to the selective 5-HT(4) receptor
      agonists prucalopride and M0003 results in a sustained non-transient effect
      during exposure; after washout, the response to a subsequent challenge with 5-HT
      shows no clear desensitization. Incubation of left atrial tissue with 5-HT
      resulted in a transient response, leading after washout to a marked
      desensitization of the subsequent response to 5-HT. The selective 5-HT(4)
      receptor agonists prucalopride and M0003 induce only very weak atrial responses
      whereas they are very effective in desensitizing the atrial response to 5-HT. The
      observations also suggest that the properties of prucalopride and M0003 to bind
      to and/or activate the 5-HT(4) receptor differ from those of 5-HT. This
      difference might have contributed to the observed desensitization. CONCLUSIONS
      AND IMPLICATIONS: The high potency of prucalopride and M0003 in desensitizing the
      response to 5-HT together with their low efficacy in the atrium emphasizes the
      cardiac safety of this class of 5-HT(4) receptor agonists.

PMID- 19154433
TI  - Comparison of mechanical and electrical activity and interstitial cells of Cajal
      in urinary bladders from wild-type and W/Wv mice.
AB  - BACKGROUND AND PURPOSE: W/W(v) and wild-type murine bladders were studied to
      determine whether the W/W(v) phenotype, which causes a reduction in, but not
      abolition of, tyrosine kinase activity, is a useful tool to study the function of
      bladder interstitial cells of Cajal (ICC). EXPERIMENTAL APPROACH:
      Immunohistochemistry, tension recordings and microelectrode recordings of
      membrane potential were performed on wild-type and mutant bladders. KEY RESULTS:
      Wild-type and W/W(v) detrusors contained c-Kit- and vimentin-immunopositive cells
      in comparable quantities, distribution and morphology. Electrical field
      stimulation evoked tetrodotoxin-sensitive contractions in wild-type and W/W(v)
      detrusor strips. Atropine reduced wild-type responses by 50% whereas a 25%
      reduction occurred in W/W(v) strips. The atropine-insensitive component was
      blocked by pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonic acid in both
      tissue types. Wild-type and W/W(v) detrusors had similar resting membrane
      potentials of -48 mV. Spontaneous electrical activity in both tissue types
      comprised action potentials and unitary potentials. Action potentials were
      nifedipine-sensitive whereas unitary potentials were not. Excitatory junction
      potentials were evoked by single pulses in both tissues. These were reduced by
      atropine in wild-type tissues but not in W/W(v) preparations. The atropine
      insensitive component was abolished by pyridoxal-5-phosphate-6-azophenyl-2',4'
      disulphonic acid in both preparations. CONCLUSIONS AND IMPLICATIONS: Bladders
      from W/W(v) mice contain c-Kit- and vimentin-immunopositive ICC. There are
      similarities in the electrical and contractile properties of W/W(v) and wild-type
      detrusors. However, significant differences were found in the pharmacology of the
      responses to neurogenic stimulation with an apparent up-regulation of the
      purinergic component. These findings indicate that the W/W(v) strain may not be
      the best model to study ICC function in the bladder.

PMID- 19154434
TI  - Incomplete dissociation of glibenclamide from wild-type and mutant pancreatic K
      ATP channels limits their recovery from inhibition.
AB  - BACKGROUND AND PURPOSE: The antidiabetic sulphonylurea, glibenclamide, acts by
      inhibiting the pancreatic ATP-sensitive K(+) (K(ATP)) channel, a tetradimeric
      complex of K(IR)6.2 and sulphonylurea receptor 1 (K(IR)6.2/SUR1)(4). At room
      temperature, recovery of channel activity following washout of glibenclamide is
      very slow and cannot be measured. This study investigates the relation between
      the recovery of channel activity from glibenclamide inhibition and the
      dissociation rate of [(3)H]-glibenclamide from the channel at 37 degrees C.
      EXPERIMENTAL APPROACH: K(IR)6.2, K(IR)6.2DeltaN5 or K(IR)6.2DeltaN10 (the latter
      lacking amino-terminal residues 2-5 or 2-10 respectively) were coexpressed with
      SUR1 in HEK cells. Dissociation of [(3)H]-glibenclamide from the channel and
      recovery of channel activity from glibenclamide inhibition were determined at 37
      degrees C. KEY RESULTS: The dissociation kinetics of [(3)H]-glibenclamide from
      the wild-type channel followed an exponential decay with a dissociation half
      time, t(1/2)(D) = 14 min; however, only limited and slow recovery of channel
      activity was observed. t(1/2)(D) for K(IR)6.2DeltaN5/SUR1 channels was 5.3 min
      and recovery of channel activity exhibited a sluggish sigmoidal time course with
      a half-time, t(1/2)(R) = 12 min. t(1/2)(D) for the DeltaN10 channel was 2.3 min;
      recovery kinetics were again sigmoidal with t(1/2)(R) approximately 4 min.
      CONCLUSIONS AND IMPLICATIONS: The dissociation of glibenclamide from the
      truncated channels is the rate-limiting step of channel recovery. The sigmoidal
      recovery kinetics are in quantitative agreement with a model where glibenclamide
      must dissociate from all four (or at least three) sites before the channel
      reopens. It is argued that these conclusions hold also for the wild-type
      (pancreatic) K(ATP) channel.

PMID- 19154436
TI  - Potent anti-inflammatory effects of two quinolinedione compounds, OQ1 and OQ21,
      mediated by dual inhibition of inducible NO synthase and cyclooxygenase-2.
AB  - BACKGROUND AND PURPOSE: Inducible nitric oxide synthase (iNOS) and cyclooxygenase
      2 (COX-2) have been suggested as key components in various inflammatory diseases.
      Here we examined the effects of new quinolinedione derivatives, 6-(4
      fluorophenyl)-amino-5,8-quinolinedione (OQ1) and 6-(2,3,4-trifluorophenyl)-amino
      5,8-quinolinedione (OQ21) on activity and expression of iNOS and COX-2 to explore
      their anti-inflammatory properties. EXPERIMENTAL APPROACH: The effects of OQ1 and
      OQ21 were assessed on lipopolysaccharide (LPS)-induced iNOS and COX-2 in murine
      macrophage cell line (RAW264.7), along with isolated enzyme assays to measure
      enzyme inhibition. Nuclear factor-kappaB (NFkappaB) activation pathways were
      investigated to elucidate mechanisms underlying OQ-mediated suppression of the
      expression of iNOS and COX-2. In vivo anti-inflammatory activities of OQ
      compounds were evaluated in mouse ear oedema, induced by topical 12-O
      tetradecanoylphorbol-13-acetate (TPA). KEY RESULTS: LPS-induced NO production in
      RAW264.7 cells was inhibited by OQ1 and OQ21 through the attenuation of iNOS
      expression as well as iNOS activity. Down-regulation of iNOS followed blocking of
      NFkappaB activation, as assessed by inhibitory kappaB degradation and
      electrophoretic mobility shift assay for NFkappaB. Synthesis and accumulation of
      prostaglandin E(2) were also suppressed by OQ1 and OQ21. LPS-induced COX-2
      expression and cellular COX-2 activities were attenuated by OQ1 and OQ21.
      Consistent with these results, OQ1 showed potent anti-inflammatory effects in
      mouse ear oedema induced by TPA. CONCLUSIONS AND IMPLICATIONS: The novel
      quinolinedione derivatives, OQ1 and OQ21, showed potent anti-inflammatory
      activity through dual inhibitory effects on iNOS and COX-2, suggesting that OQ
      derivatives might provide a new therapeutic modality for chronic inflammatory
      diseases, refractory to conventional drug therapies.

PMID- 19154435
TI  - Endothelium-dependent contractions in SHR: a tale of prostanoid TP and IP
      receptors.
AB  - In the aorta of spontaneously hypertensive rats (SHR), the endothelial
      dysfunction is due to the release of endothelium-derived contracting factors
      (EDCFs) that counteract the vasodilator effect of nitric oxide, with no or minor
      alteration of its production. The endothelium-dependent contractions elicited by
      acetylcholine (ACh) involve an increase in endothelial [Ca(2+)](i), the
      production of reactive oxygen species, the activation of endothelial
      cyclooxygenase-1, the diffusion of EDCF and the subsequent stimulation of smooth
      muscle cell TP receptors. The EDCFs released by ACh have been identified as
      PGH(2) and paradoxically prostacyclin. Prostacyclin generally acts as an
      endothelium-derived vasodilator, which, by stimulating IP receptors, produces
      hyperpolarization and relaxation of the smooth muscle and inhibits platelet
      aggregation. In the aorta of SHR and Wistar-Kyoto rats, prostacyclin is the
      principal metabolite of arachidonic acid released by ACh. However, in SHR aorta,
      prostacyclin does not produce relaxations but activates the TP receptors on
      vascular smooth muscle cells and produces contraction. The IP receptor is not
      functional in the aortic smooth muscle cells of SHR as early as 12 weeks of age,
      but its activity is not reduced in platelets. Therefore, prostacyclin in the rule
      protects the vascular wall, but in the SHR aorta it can contribute to endothelial
      dysfunction. Whether or not prostacyclin plays a detrimental role as an EDCF in
      other animal models or in human remains to be demonstrated. Nevertheless, because
      EDCFs converge to activate TP receptors, selective antagonists of this receptor,
      by preventing endothelium-dependent contractions, curtail the endothelial
      dysfunction in diseases such as hypertension and diabetes.

PMID- 19154437
TI  - BGC20-1531, a novel, potent and selective prostanoid EP receptor antagonist: a
      putative new treatment for migraine headache.
AB  - BACKGROUND AND PURPOSE: Prostanoid EP(4) receptor antagonists may have
      therapeutic utility in the treatment of migraine since EP(4) receptors have been
      shown to be involved in prostaglandin (PG)E(2)-induced cerebral vascular
      dilatation, which may be an important contributor to migraine pain. This study
      reports the pharmacological characterization of BGC20-1531, a novel EP(4)
      receptor antagonist. EXPERIMENTAL APPROACH: BGC20-1531 was characterized in
      radioligand binding and in vitro functional assays employing recombinant and
      native EP(4) receptors. Changes in canine carotid haemodynamics were used to
      assess the pharmacodynamic profile of BGC20-1531 in vivo. KEY RESULTS: BGC20-1531
      exhibited high affinity at recombinant human EP(4) receptors expressed in cell
      lines (pK(B) 7.6) and native EP(4) receptors in human cerebral and meningeal
      artery (pK(B) 7.6-7.8) but showed no appreciable affinity at a wide range of
      other receptors (including other prostanoid receptors), channels, transporters
      and enzymes (pKi < 5). BGC20-1531 competitively antagonized PGE(2)-induced
      vasodilatation of human middle cerebral (pK(B) 7.8) and meningeal (pK(B) 7.6)
      arteries in vitro, but had no effect on responses induced by PGE(2) on coronary,
      pulmonary or renal arteries in vitro. BGC20-1531 (1-10 mg.kg(-1) i.v.) caused a
      dose-dependent antagonism of the PGE(2)-induced increase in canine carotid blood
      flow in vivo. CONCLUSIONS AND IMPLICATIONS: BGC20-1531 is a potent and selective
      antagonist at EP(4) receptors in vitro and in vivo, with the potential to
      alleviate the symptoms of migraine that result from cerebral vasodilatation.
      BGC20-1531 is currently in clinical development for the treatment of migraine
      headache.

PMID- 19154438
TI  - Ontogenic changes of the control by phosphodiesterase-3 and -4 of 5-HT responses
      in porcine heart and relevance to human atrial 5-HT(4) receptors.
AB  - BACKGROUND AND PURPOSE: Atrial inotropic responses to 5-HT mediated through 5
      HT(4) receptors fade, presumably through phosphodiesterase (PDE) activity. We
      investigated the influence of a selective inhibitor of PDE3 (cilostamide) or of
      PDE4 (rolipram) on the fade of 5-HT responses in atrial muscle. EXPERIMENTAL
      APPROACH: 5-HT responses were compared, ex vivo, on sinoatrial beating rate of
      newborn piglets, porcine atrial and ventricular force, and human atrial force.
      cAMP levels were assessed in piglet atrium. KEY RESULTS: 5-HT-evoked sinoatrial
      tachycardia did not fade and was not potentiated by cilostamide (300 nmol.L(-1))
      or rolipram (1 micromol.L(-1)). Inotropic responses to 5-HT faded in atria from
      piglets, adolescent pigs and humans. Cilostamide reduced atrial fade of 5-HT
      responses in adolescent pigs and humans but not in newborn piglets. Cilostamide
      disclosed 5-HT ventricular responses in newborn, but not adolescent pigs.
      Rolipram reduced fade of atrial 5-HT responses in newborn and adolescent pigs but
      not in humans. Concurrent cilostamide + rolipram abolished fade of 5-HT responses
      in porcine left atria and facilitated ventricular 5-HT responses, but did not
      reduce residual fade in human atrium in the presence of cilostamide. 5-HT-evoked
      increases in cAMP faded; fade was abolished by concurrent cilostamide + rolipram.
      CONCLUSIONS AND IMPLICATIONS: PDE3-induced control of porcine 5-HT responses
      differed in atrium and ventricle and changed with age. PDE3 and PDE4 jointly
      prevented fade of inotropic and cAMP responses to 5-HT in porcine atrium. Unlike
      porcine atria, only PDE3 induced fade of 5-HT responses in human atria.

PMID- 19154439
TI  - A novel diketopiperazine improves functional recovery given after the onset of 6
      OHDA-induced motor deficit in rats.
AB  - BACKGROUND AND PURPOSE: Cyclo-L-glycyl-L-2-allylproline (NNZ-2591), a modified
      diketopiperazine, is neuroprotective and improves long-term function after
      hypoxic-ischaemic brain injury in rats. The present studies were designed to
      examine both the neuroprotective and neurotrophic actions of NNZ-2591 on
      neurochemical and behavioural changes in a rat model of Parkinson's disease.
      EXPERIMENTAL APPROACH: To examine its protective effect, either NNZ-2591 (20
      ng.day(-1)) or saline was given intracerebroventricularly for 3 days starting 2 h
      after 6-hydroxydopamine (6-OHDA) induced unilateral striatal lesion. In a
      subsequent experiment either NNZ-2591 (0.2, 1 and 5 mg.day(-1), s.c.) or saline
      was administered daily for 14 days starting 2 weeks after the lesion. Behavioural
      and neurochemical outcomes were examined using the adjusting step test and
      immunohistochemical staining. KEY RESULTS: Cyclo-L-glycyl-L-2-allylproline given
      2 h after the lesion reduced the degree of motor deficit compared with the saline
      treated group. Delayed treatment with NNZ-2591, initiated after the onset of
      motor deficit, significantly improved motor function from week 7 onwards compared
      with the saline-treated group. Neither treatment regime altered nigrostriatal
      dopamine depletion. NNZ-2591 significantly enhanced the expression of
      doublecortin-positive neuroblasts in the sub-ventricular zone. CONCLUSIONS AND
      IMPLICATIONS: These studies reveal that early treatment with NNZ-2591 protects
      against the motor deficit induced by 6-OHDA and that treatment initiated after
      the establishment of motor impairment significantly improves long-term motor
      function. These effects of NNZ-2591 on functional recovery were independent of
      dopamine depletion and also appeared not to be symptomatic as the improved motor
      function was long-lasting. NNZ-2591 has potential as a therapeutic agent for
      neurodegenerative disorders.

PMID- 19154440
TI  - Mechanism of asynchronous Ca(2+) waves underlying agonist-induced contraction in
      the rat basilar artery.
AB  - BACKGROUND AND PURPOSE: Uridine 5'-triphosphate (UTP) is a potent vasoconstrictor
      of cerebral arteries and induces Ca(2+) waves in vascular smooth muscle cells
      (VSMCs). This study aimed to determine the mechanisms underlying UTP-induced
      Ca(2+) waves in VSMCs of the rat basilar artery. EXPERIMENTAL APPROACH: Isometric
      force and intracellular Ca(2+) ([Ca(2+)](i)) were measured in endothelium-denuded
      rat basilar artery using wire myography and confocal microscopy respectively. KEY
      RESULTS: Uridine 5'-triphosphate (0.1-1000 micromol.L(-1)) concentration
      dependently induced tonic contraction (pEC(50) = 4.34 +/- 0.13), associated with
      sustained repetitive oscillations in [Ca(2+)](i) propagating along the length of
      the VSMCs as asynchronized Ca(2+) waves. Inhibition of Ca(2+) reuptake in
      sarcoplasmic reticulum (SR) by cyclopiazonic acid abolished the Ca(2+) waves and
      resulted in a dramatic drop in tonic contraction. Nifedipine reduced the
      frequency of Ca(2+) waves by 40% and tonic contraction by 52%, and the nifedipine
      insensitive component was abolished by SKF-96365, an inhibitor of receptor- and
      store-operated channels, and KB-R7943, an inhibitor of reverse-mode Na(+)/Ca(2+)
      exchange. Ongoing Ca(2+) waves and tonic contraction were also abolished after
      blockade of inositol-1,4,5-triphosphate-sensitive receptors by 2
      aminoethoxydiphenylborate, but not by high concentrations of ryanodine or
      tetracaine. However, depletion of ryanodine-sensitive SR Ca(2+) stores prior to
      UTP stimulation prevented Ca(2+) waves. CONCLUSIONS AND IMPLICATIONS: Uridine 5'
      triphosphate-induced Ca(2+) waves may underlie tonic contraction and appear to be
      produced by repetitive cycles of regenerative Ca(2+) release from the SR through
      inositol-1,4,5-triphosphate-sensitive receptors. Maintenance of Ca(2+) waves
      requires SR Ca(2+) reuptake from Ca(2+) entry across the plasma membrane via L
      type Ca(2+) channels, receptor- and store-operated channels, and reverse-mode
      Na(+)/Ca(2+) exchange.

PMID- 19154442
TI  - Complex adrenergic and inflammatory mechanisms contribute to phase 2 ventricular
      arrhythmias in anaesthetized rats.
AB  - BACKGROUND AND PURPOSE: The mechanisms responsible for phase 2 (infarct-related)
      ventricular arrhythmias remain unclear. We have investigated the role of alpha(1)
      and beta(1) adrenoceptor activation and the interaction of this with infarct
      neutrophil accumulation, in anaesthetized rats. EXPERIMENTAL APPROACH: Neutrophil
      replete Sprague-Dawley rats (n = 8-9 per group) were anaesthetized and randomized
      to receive vehicle, prazosin (0.5 mg.kg(-1) i.v.), atenolol (4 mg.kg(-1) i.v.) or
      their combination prior to left main coronary artery occlusion. A further group
      was depleted of neutrophils and received both atenolol and prazosin. Coronary
      ligation in all groups was maintained for 240 min. KEY RESULTS: Atenolol and
      prazosin treatment lowered heart rates and blood pressures respectively, but
      neither agent given alone affected the incidence of phase 2 ventricular
      tachycardia or fibrillation. However, co-administration of atenolol with prazosin
      reduced phase 2 ventricular premature beats (log(10)-transformed totals were 1.25
      +/- 0.26 vs. 2.43 +/- 0.18 in controls; P < 0.05). Neutrophil depletion
      attenuated this antiarrhythmic effect (log(10)-transformed total ventricular
      premature beats were 1.66 +/- 0.35; P > 0.05 vs. controls). CONCLUSIONS AND
      IMPLICATIONS: Phase 2 arrhythmias appear to depend in part on a complex
      interaction between catecholamines and neutrophils. A model of this interaction
      is proposed.

PMID- 19154441
TI  - Eicosapentaenoic acid inhibits voltage-gated sodium channels and invasiveness in
      prostate cancer cells.
AB  - BACKGROUND AND PURPOSE: The voltage-gated Na(+) channels (Na(v)) and their
      corresponding current (I(Na)) are involved in several cellular processes, crucial
      to metastasis of cancer cells. We investigated the effects of eicosapentaenoic
      (EPA), an omega-3 polyunsaturated fatty acid, on I(Na) and metastatic functions
      (cell proliferation, endocytosis and invasion) in human and rat prostate cancer
      cell lines (PC-3 and Mat-LyLu cells). EXPERIMENTAL APPROACH: The whole-cell
      voltage clamp technique and conventional/quantitative real-time reverse
      transcriptase polymerase chain reaction analysis were used. The presence of Na(v)
      proteins was shown by immunohistochemical methods. Alterations in the fatty acid
      composition of phospholipids after treatment with EPA and metastatic functions
      were also examined. KEY RESULTS: A transient inward Na(+) current (I(Na)), highly
      sensitive to tetrodotoxin, and Na(V) proteins were found in these cells.
      Expression of Na(V)1.6 and Na(V)1.7 transcripts (SCN8A and SCN9A) was predominant
      in PC-3 cells, while Na(V)1.7 transcript (SCN9A) was the major component in Mat
      LyLu cells. Tetrodotoxin or synthetic small interfering RNA targeted for SCN8A
      and SCN9A inhibited metastatic functions (endocytosis and invasion), but failed
      to inhibit proliferation in PC-3 cells. Exposure to EPA produced a rapid and
      concentration-dependent suppression of I(Na). In cells chronically treated (up to
      72h) with EPA, the EPA content of cell lipids increased time-dependently, while
      arachidonic acid content decreased. Treatment of PC-3 cells with EPA decreased
      levels of mRNA for SCN9A and SCN8A, cell proliferation, invasion and endocytosis.
      CONCLUSION AND IMPLICATIONS: Treatment with EPA inhibited I(Na) directly and also
      indirectly, by down-regulation of Na(v) mRNA expression in prostate cancer cells,
      thus inhibiting their metastatic potential.

PMID- 19154443
TI  - Roflumilast, a phosphodiesterase 4 inhibitor, alleviates bleomycin-induced lung
      injury.
AB  - BACKGROUND AND PURPOSE: The effects of a phosphodiesterase 4 (PDE4) inhibitor,
      roflumilast, on bleomycin-induced lung injury were explored in 'preventive' and
      'therapeutic' protocols and compared with glucocorticoids. EXPERIMENTAL APPROACH:
      Roflumilast (1 and 5 mg.kg(-1).d(-1), p.o.) or dexamethasone (2.5 mg.kg(-1).d(
      1), p.o.) was given to C57Bl/6J mice from day 1 to 14 (preventive) or day 7 to 21
      (therapeutic) after intratracheal bleomycin (3.75 U.kg(-1)). In Wistar rats,
      roflumilast (1 mg.kg(-1).d(-1), p.o.) was compared with methylprednisolone (10
      mg.kg(-1).d(-1), p.o.) from day 1 to 21 (preventive) or from day 10 to 21
      (therapeutic), following intratracheal instillation of bleomycin (7.5 U.kg(-1)).
      Analyses were performed at the end of the treatment periods. KEY RESULTS:
      Preventive. Roflumilast reduced bleomycin-induced lung hydroxyproline, lung
      fibrosis and right ventricular hypertrophy; muscularization of intraacinar
      pulmonary vessels was also attenuated. The PDE4 inhibitor diminished bleomycin
      induced transcripts for tumour necrosis factor (TNFalpha), transforming growth
      factor (TGFbeta), connective tissue growth factor, alphaI(I)collagen, endothelin
      1 and the mucin, Muc5ac, in lung, and reduced bronchoalveolar lavage fluid levels
      of TNFalpha, interleukin-13, TGFbeta, Muc5ac, lipid hydroperoxides and
      inflammatory cell counts. Therapeutic. In mice, roflumilast but not dexamethasone
      reduced bleomycin-induced lung alphaI(I)collagen transcripts, fibrosis and right
      ventricular hypertrophy. Similar results were found in the rat. CONCLUSIONS AND
      IMPLICATIONS: Roflumilast prevented the development of bleomycin-induced lung
      injury, and alleviated the lung fibrotic and vascular remodeling response to
      bleomycin in a therapeutic protocol, the latter being resistant to
      glucocorticoids.

PMID- 19154444
TI  - Tachykinin receptor modulation of cyclooxygenase-2 expression in human
      polymorphonuclear leucocytes.
AB  - BACKGROUND AND PURPOSE: We investigated the ability of natural and synthetic
      selective NK receptors agonists and antagonists to modulate cyclooxygenase-2 (COX
      2) expression in human polymorphonuclear leucocytes (PMNs). EXPERIMENTAL
      APPROACH: The presence of all three tachykinin in PMNs was assessed by Western
      blot and PCR techniques. Natural and synthetic ligands selective for the
      tachykinin receptors were used to modulate COX-2 protein (measured with Western
      blotting) and activity [as prostaglandin E(2) (PGE(2)) output]. Effects of
      substance P (SP) on phosphorylation of mitogen-activated protein kinases (MAPKs)
      and nuclear factor-kappa B (NF-kappaB) activation were studied to analyse the
      signalling pathway involved in COX-2 up-regulation mediated by SP. KEY RESULTS:
      Stimulation of NK receptors with the natural ligands SP, neurokinin A (NKA) and
      neurokinin B, in the pmol.L(-1)-micromol.L(-1) concentration range, modulated COX
      2 expression and PGE(2) release in a concentration- and time-dependent manner.
      Experiments with synthetic selective agonists [Sar(9), Met(O(2))(11)]SP, [beta
      Ala(8)] NKA(4-10), senktide or selective antagonists L703,606, SR48,968 or
      SR142801, confirmed that COX-2 up-regulation was mediated by NK receptors. We
      found that mainly p38, p42 and p46 MAPKs were phosphorylated by SP and SB202190,
      PD98059 and SP600125, which are selective inhibitors of these kinases, blocked SP
      induced COX-2 expression. SP also induced nuclear translocation of NF-kappaB
      concentration-dependently, with a maximum effect at 1 nmol.L(-1). CONCLUSIONS AND
      IMPLICATIONS: Human PMNs possess functional NK(1), NK(2) and NK(3) receptors,
      which mediate the induction of COX-2 expression and NF-kappaB activation by SP.

PMID- 19154446
TI  - The availability of prescription-only analgesics purchased from the internet in
      the UK.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Increasing numbers of people are
      accessing medicines from the internet. This online market is poorly regulated and
      represents a potential threat to the health of patients and members of the
      public. WHAT THIS STUDY ADDS: Prescription-only analgesics, including controlled
      opioids, are readily available to the UK public through internet pharmacies that
      are easily identified by popular search engines. The majority of websites do not
      require the customer to possess a valid prescription for the drug. Less than half
      provide an online health screen to assess suitability for supply. The majority
      have no registered geographical location. Analgesic medicines are usually
      purchased at prices significantly above British National Formulary prices and are
      often supplied in large quantities. These findings are of particular relevance to
      pain-management specialists who are trying to improve the rational use of
      analgesic drugs. AIMS: To explore the availability to the UK population of
      prescription-only analgesics from the internet. METHODS: Websites were identified
      by using several keywords in the most popular internet search engines. From 2000
      websites, details of 96 were entered into a database. RESULTS: Forty-six (48%)
      websites sold prescription analgesics, including seven opioids, two non-opioids
      and 18 nonsteroidal anti-inflammatory drugs. Thirty-five (76%) of these did not
      require the customer to possess a valid prescription. CONCLUSION: Prescription
      only analgesics, including controlled opioids, are readily available from
      internet websites, often without a valid prescription.

PMID- 19154445
TI  - Signal transduction and functional selectivity of F15599, a preferential post
      synaptic 5-HT1A receptor agonist.
AB  - BACKGROUND AND PURPOSE: Activation of post-synaptic 5-HT(1A) receptors may
      provide enhanced therapy against depression. We describe the signal transduction
      profile of F15599, a novel 5-HT(1A) receptor agonist. EXPERIMENTAL APPROACH:
      F15599 was compared with a chemical congener, F13714, and with (+)8-OH-DPAT in
      models of signal transduction in vitro and ex vivo. KEY RESULTS: F15599 was
      highly selective for 5-HT(1A) receptors in binding experiments and in [(35)S]
      GTPgammaS autoradiography of rat brain, where F15599 increased labelling in
      regions expressing 5-HT(1A) receptors. In cell lines expressing h5-HT(1A)
      receptors, F15599 more potently stimulated extracellular signal-regulated kinase
      (ERK1/2) phosphorylation, compared with G-protein activation, internalization of
      h5-HT(1A) receptors or inhibition of cAMP accumulation. F13714, (+)8-OH-DPAT and
      5-HT displayed a different rank order of potency for these responses. F15599
      stimulated [(35)S]-GTPgammaS binding more potently in frontal cortex than raphe.
      F15599, unlike 5-HT, more potently and efficaciously stimulated G(alphai) than
      G(alphao) activation. In rat prefrontal cortex (a region expressing post-synaptic
      5-HT(1A) receptors), F15599 potently activated ERK1/2 phosphorylation and
      strongly induced c-fos mRNA expression. In contrast, in raphe regions (expressing
      pre-synaptic 5-HT(1A) receptors) F15599 only weakly or did not induce c-fos mRNA
      expression. Finally, despite its more modest affinity in vitro, F15599 bound to 5
      HT(1A) receptors in vivo almost as potently as F13714. CONCLUSIONS AND
      IMPLICATIONS: F15599 showed a distinctive activation profiles for 5-HT(1A)
      receptor-mediated signalling pathways, unlike those of reference agonists and
      consistent with functional selectivity at 5-HT(1A) receptors. In rat, F15599
      potently activated signalling in prefrontal cortex, a feature likely to underlie
      its beneficial effects in models of depression and cognition.

PMID- 19154447
TI  - Effectiveness and safety of short vs. long duration of antibiotic therapy for
      acute bacterial sinusitis: a meta-analysis of randomized trials.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Treatment guidelines generally support
      that a 10-14-day antibiotic regimen should be administered to uncomplicated acute
      bacterial sinusitis patients. However, the level of evidence for such a
      recommendation is rather weak. Treatment of such duration may have disadvantages
      compared with a shorter duration but equally effective regimen, including the
      promotion of bacterial drug resistance, poorest patient compliance, higher
      toxicity, and a greater overall economic burden. WHAT THIS STUDY ADDS: The
      findings of this meta-analysis suggest that short-course antibiotic treatment has
      similar effectiveness to longer-course treatment for patients with acute
      uncomplicated bacterial sinusitis, when treatment is warranted. However, we
      should underscore the importance of the clinician's own assessment, so that
      antimicrobial therapy should not inappropriately be curtailed in a patient not
      adequately responding to the regimen administered. We sought to evaluate the
      effectiveness and safety of short-course antibiotic treatment for acute bacterial
      sinusitis (ABS) compared with longer duration treatment. We performed a meta
      analysis of randomized controlled trials (RCTs), identified by searching PubMed
      and the Cochrane Central Register of Controlled Trials. We included RCTs that
      compared short-course (up to 7 days) vs. long-course therapy (> or =2 days longer
      than short-course), with the same antimicrobial agent, in the same daily dosage,
      for patients with ABS. Twelve RCTs (10 double-blinded) involving adult patients
      with radiologically confirmed ABS were included. There was no difference in the
      comparison of short-course (3-7 days) with long-course treatment (6-10 days)
      regarding clinical success [12 RCTs, 4430 patients, fixed effect model (FEM),
      odds ratio (OR) 0.95, 95% confidence interval (CI) 0.81, 1.12]; microbiological
      efficacy; relapses; adverse events (10 RCTs, 4172 patients, random effects model,
      OR 0.88, 95% CI 0.71, 1.09); or withdrawals due to adverse events. In the
      sensitivity analysis comparing 5- vs. 10-day regimens, clinical success was
      similar, although adverse events were fewer with short-course treatment (5 RCTs,
      2151 patients, FEM, OR 0.79, 95% CI 0.63, 0.98). Although antibiotics for acute
      sinusitis should be reserved for select patients with substantial probability of
      bacterial disease, accurate clinical diagnosis is often difficult to attain.
      Short-course antibiotic treatment had comparable effectiveness to a longer course
      of therapy for ABS. Shortened treatment, particularly for patients without severe
      disease and complicating factors, might lead to fewer adverse events, better
      patient compliance, lower rates of resistance development and fewer costs.

PMID- 19154448
TI  - The results of concurrent chemo-radiotherapy for recurrence after treatment with
      bacillus Calmette-Guerin for non-muscle-invasive bladder cancer: is immediate
      cystectomy always necessary?
AB  - OBJECTIVES: To report our original experience in patients in whom bacille
      Calmette-Guerin (BCG) therapy has failed for T1 bladder cancer with subsequent
      progression to T2 disease treated with chemo-radiotherapy, as the management of
      recurrent high-grade T1 bladder cancer after failed BCG therapy is challenging,
      and radical cystectomy is the standard treatment because there are no well
      established second-line bladder-preserving therapies. PATIENTS AND METHODS: From
      1988 to 2002, 18 patients with T2 recurrence after failure of BCG therapy for T1
      bladder cancer were treated with chemo-radiotherapy at the authors' institution.
      Patients received a visibly complete transurethral resection of the bladder
      tumour (TURBT) and concurrent chemo-radiotherapy with a mid-treatment evaluation
      after 40 Gy. Patients with less than a complete response had a prompt cystectomy;
      the others completed radiotherapy to 64-65 Gy. The primary treatment outcome was
      freedom from cystectomy due to recurrence not treatable by conservative measures;
      secondary outcomes included disease-specific (DSS) and overall survival (OS).
      RESULTS: With a median follow-up of 7.0 years, only one patient had persistent
      tumour at re-staging TURBT and had an immediate cystectomy. Of the remaining 17
      patients, 10 (59%) were free of any bladder recurrence. The actuarial 7-year DSS
      and OS were 70% and 58%, respectively. At 7 years, 54% of patients were alive
      with intact bladders and free of invasive recurrence. CONCLUSIONS: In this study
      we specifically evaluated patients with apparently small muscle-invasive
      recurrences after BCG treatment for T1 bladder cancer. Selective bladder
      preservation with chemo-radiotherapy is possible, with low morbidity and a high
      chance of long-term bladder control. If successful in treating T2 recurrences
      after BCG therapy, it now seems timely to critically evaluate chemo-radiotherapy
      as an alternative to immediate cystectomy in the management of patients with T1
      recurrences after BCG.

PMID- 19154449
TI  - Does a history of previous surgery or radiation to the prostate affect outcomes
      of robot-assisted radical prostatectomy?
AB  - OBJECTIVE: To evaluate retrospectively whether or not previous treatment to the
      prostate alters the perioperative outcomes from robot-assisted radical
      prostatectomy (RARP) after the initial 'learning curve', as there are conflicting
      data on outcomes of RP in patients with previous treatment to the prostate.
      PATIENTS AND METHODS: We retrospectively reviewed the charts of patients who had
      RARP between March 2005 and August 2007, and analysed demographic, perioperative
      variables and pathological data. In all, 510 patient charts were reviewed,
      identifying 24 patients with a history of previous treatment to the prostate
      including transurethral resection or incision of the prostate, transurethral
      microwave therapy, transurethral needle ablation, photoselective vaporization,
      simple prostatectomy, external beam radiotherapy, brachytherapy, and open bladder
      neck reconstruction (group 1) and 486 with no previous treatment (group 2).
      RESULTS: There was no significant difference between the groups in body mass
      index, clinical stage, grade or prostate volume, but the patients in group 1 were
      older (70 vs 65 years, P = 0.001). Outcome analysis comparing groups 1 and 2
      showed an estimated blood loss of 155 vs 137 mL, length of hospital stay of 2.2
      vs 1.5 days, operative duration of 200 vs 186 min and catheter time of 12 vs 8
      days, respectively; only the last was statistically significant (P = 0.03). There
      was an 8.3% and 6.8% complication rate in groups 1 and 2, respectively, and the
      respective overall positive margin rate was 20.8% and 22.6%. CONCLUSIONS: A
      history of previous treatment of the prostate does not appear to compromise the
      perioperative outcomes of RARP.

PMID- 19154450
TI  - Prostate-specific antigen changes and prostate cancer in hypogonadal men treated
      with testosterone replacement therapy.
AB  - OBJECTIVES: To retrospectively review hypogonadal men receiving testosterone
      replacement therapy (TRT), and evaluate the changes in prostate-specific antigen
      (PSA) levels over an extended period, and thus evaluate the occurrence of
      prostate cancer, as a primary concern in treating late-onset hypogonadism (LOH)
      is the potential increased risk of prostate cancer; we also recorded the
      cardiovascular effects of TRT. PATIENTS AND METHODS: In all, 81 hypogonadal men
      (mean age 56.8 years) were followed for a mean (range) of 33.8 (6-144) months
      after starting TRT. All men had a normal baseline PSA level before TRT and had
      routine laboratory investigations, including measurements of body mass index
      (BMI), haematocrit, lipid profile, and liver function tests (LFTs). Testosterone
      and PSA levels were assessed every 6-12 months. Patients with a biopsy-confirmed
      or recent history of prostatitis before treatment were excluded. TRT was
      discontinued in men who developed prostate cancer. RESULTS: Before and 36 months
      after treatment the total testosterone levels were 241.1 and 379.8 ng/dL (P <
      0.05), respectively. Four men (4.9%) developed prostate cancer at a mean (range)
      of 32.5 (22-41) months after starting TRT. In men without prostate cancer
      (95.1%), PSA levels did not increase significantly at 1-year intervals for 5
      years. There was no statistical difference in PSA level change from baseline to
      36 months when patients without prostate cancer were stratified into groups
      according to age (< or =50, 55-65 and > or =70 years). In men with prostate
      cancer there was an increase in mean PSA level from baseline to 18 months of 1.8
      ng/mL, and to 36 months of 3.2 ng/mL (P < 0.05). Total cholesterol improved from
      203.8 to 166.6 mg/dL (P < 0.05) after 36 months of TRT; the BMI, haematocrit and
      LFTs did not change significantly. CONCLUSIONS: LOH is an increasingly prevalent
      disease characterized by a symptomatically low testosterone level, and TRT is
      effective in normalizing serum testosterone levels, providing a beneficial
      cardiovascular effect, and improving sexual function and overall quality of life.
      PSA levels remain stable after normalization of testosterone for > or =5 years,
      prostate cancer can be effectively diagnosed and treated in men taking TRT, and
      the incidence of prostate cancer among men with LOH on TRT is no greater than
      that in the general population.

PMID- 19154451
TI  - Urokinase-plasminogen-activator receptor expression in disseminated tumour cells
      in the bone marrow and peripheral blood of patients with clinically localized
      prostate cancer.
AB  - OBJECTIVE To evaluate the expression of urokinase-plasminogen-activator receptor
      (uPA-R) in disseminated tumour cells (DTC) in bone marrow (BM) and peripheral
      blood (PB) of patients with clinically localized prostate cancer before radical
      prostatectomy (RP), and to assess the associations with pathological variables
      and prognosis. PATIENTS AND METHODS In all, 52 patients (47 with clinically
      localized cancer and five with benign prostatic hyperplasia, BPH, as controls)
      were prospectively enrolled. BM and PB samples were drawn before surgery. DTC
      were enriched using a commercial system, cytokeratin (CK) 8/18 was used to detect
      DTC, and uPA-R expression was detected by dual-immunostaining of the DTC. The
      final pathology of the RP specimen was compared with the results of
      immunostaining. Follow-up was initiated to detect tumour relapse (defined as a
      prostate-specific antigen (PSA) level of > or =0.2 ng/mL). RESULTS Overall, there
      was expression of 'CK + uPA-R' in 60% of the BM and in 19% of the PB specimens.
      Expression of this marker in BM was most significantly increased in those with
      unfavourable Gleason scores (P = 0.004), followed by high-risk cancer (P =
      0.005). The relative risk for CK + uPA-R expression in the BM was 3.1 times
      higher in high-risk than in low-risk prostate cancer. No relevant expression
      rates were detected for PB. In the control group, no patient showed CK or uPA-R
      expression in BM or PB. The PSA-recurrence free survival was significantly lower
      in patients with CK + uPA-R-positive BM cells (P = 0.01). CONCLUSION In this
      pilot study, the preoperative detection rate of CK + uPAR expression in BM of
      patients with prostate cancer increased with Gleason score and in those with high
      risk disease. All patients with a later PSA relapse had had uPA-R expression in
      their DTC from the BM. DTC with uPA-R expression was an adverse prognostic factor
      for prostate cancer.

PMID- 19154452
TI  - Favourable outcomes of patients with clinical stage T3N0M0 bladder cancer treated
      with induction low-dose chemo-radiotherapy plus partial or radical cystectomy vs
      immediate radical cystectomy: a single-institutional retrospective comparative
      study.
AB  - OBJECTIVES: To address the role of neoadjuvant concurrent chemo-radiotherapy
      (CRT) in muscle-invasive bladder cancer, by comparing retrospectively the
      oncological outcomes between a low-dose CRT (LCRT) plus partial cystectomy (PC)
      or radical cystectomy (RC) protocol and an immediate RC protocol. PATIENTS AND
      METHODS: From 1997 to 2007, 119 patients with clinical stage T2-4aN0M0 bladder
      cancer received LCRT consisting of RT of 40 Gy in 4 weeks concurrently with two
      cycles of chemotherapy with cisplatin (20 mg/day for 5 days) during the first and
      fourth week of RT. Subsequently, 24 (20%) and 65 patients (55%) had PC and RC,
      respectively, while 30 (25%) had no curative surgery; the median follow-up was 36
      months. From 1983 to 1997, 73 patients had an immediate RC; 29 (41%) received
      cisplatin-based adjuvant chemotherapy, and the median follow-up was 46 months.
      Oncological outcomes were compared retrospectively between these groups. RESULTS:
      The cancer-specific survival (CSS) rate at 5 years was 75% and 61% for the LCRT
      protocol and immediate RC protocol, respectively (P = 0.11). In patients with
      clinical stage T3N0M0 the LCRT protocol gave significantly better survival rates
      than the immediate RC protocol, with 5-year CSS rates of 62% vs 27% (P = 0.006),
      while being comparable in those with clinical stage T2N0M0 disease (89% vs 88%, P
      = 0.84). In patients with clinical stage T3N0M0 the LCRT protocol provided a
      lower 5-year recurrence rate at distant sites than the immediate RC protocol (31%
      vs 62%, P = 0.09). CONCLUSIONS: The LCRT plus PC or RC protocol gave
      significantly better survival rates than the historical, immediate RC protocol in
      patients with clinical stage T3N0M0 bladder cancer, suggesting that neoadjuvant
      CRT possibly has survival benefits for such patients.

PMID- 19154453
TI  - Ureteric frozen sections during radical cystectomy for transitional cell
      carcinoma of the bladder--to do or not to do?

PMID- 19154454
TI  - Concomitant repeated intravesical injections of botulinum toxin-type A and
      laparoscopic antegrade continence enema; a new solution for an old problem.
AB  - OBJECTIVE: To report our experience of treating bladder and bowel dysfunction in
      children with myelomeningocele, with simultaneous laparoscopic antegrade
      continence enema (LACE) and repeated intravesical injection of botulinum toxin
      type A (BTX-A). PATIENTS AND METHODS: Six girls and 14 boys (mean age, 8.7 years)
      with myelomeningocele were included in this study. All patients had received one
      or two intravesical injection(s) of BTX-A, but had persistent fecal incontinence
      or constipation despite improved urinary symptoms. We performed a two-port
      laparoscopic appendicostomy, immediately after repeated intravesical injection of
      BTX-A, through a V-shaped skin flap at McBurney's point. The stoma was finally
      covered by a quadrilateral skin flap, using the 'VQ' technique. The degree of
      urinary incontinence and bowel dysfunction were determined in each patient, and
      conventional urodynamic studies were performed 4 months after each injection.
      RESULTS: All patients were followed-up for a mean (range) of 19.1 (14-33) months.
      Urinary continence improved significantly after the first injection, and remained
      constant after repeat injections. The maximum detrusor pressure, bladder
      compliance and capacity improved significantly (P < 0.001) compared with
      baseline. Interestingly, the simultaneous intravesical BTX-A injection/LACE
      procedure significantly improved all urodynamic variables compared with the
      values obtained after the last BTX-A injection alone. The laparoscopic procedure
      was well tolerated, and 19 (95%) children were nappy-free at the final follow-up.
      Only two patients had stoma stenosis, and one patient had minor stoma leakage.
      CONCLUSION: Concomitant repeat intravesical injection of BTX-A and LACE can
      effectively manage bladder and bowel dysfunction in children with
      myelomeningocele. The procedure may further contribute to improve bladder
      urodynamic function, as effective evacuation of the bowel provides more room for
      bladder distension.

PMID- 19154455
TI  - Use of forearm free-flap phalloplasty in bladder exstrophy adults.
AB  - OBJECTIVE: To assess the long-term outcome and cosmetic results of forearm free
      flap phalloplasty for correcting micropenis associated with bladder exstrophy in
      men. PATIENTS AND METHODS: From 1992 to 2000, six men with bladder exstrophy and
      unsatisfactory penile appearance underwent phalloplasty at our institution. The
      mean (range) follow-up was 113 (62-153) months. The surgical procedure consisted
      of a modified radial free-flap phalloplasty and prosthesis implantation. One
      stage urethroplasty was electively performed according to the patient's voiding
      pattern. Early and late complications were recorded and quality of life after
      phalloplasty was assessed. RESULTS: The mean (range) age was 21.2 (17-26) years
      and flap survival was 100%. Two incontinent patients underwent immediate perineal
      urethrostomy. One sepsis occurred, requiring the removal of the penile prosthesis
      and a cutaneous continent urinary diversion; this patient was the only one to
      complain about the outcome. Two anastomotic urethral strictures were
      conservatively treated by endoscopic urethrotomy and only one patient underwent
      subsequent urethral self-dilatations. Five patients were very satisfied with the
      cosmesis of the neophallus and three patients reported having regular sexual
      intercourse. CONCLUSIONS: Although short, this series indicates the low incidence
      of early complications and the excellent long-term satisfaction with forearm free
      flap phalloplasty in bladder exstrophy. Phalloplasty has potential indications
      when adult exstrophy patients are dissatisfied with the cosmetic appearance of
      their external genitalia or have unsatisfactory sexual intercourse.

PMID- 19154456
TI  - Failure of monotherapy in primary monosymptomatic enuresis: a combined
      desmopressin and propiverine treatment regimen improves efficacy outcomes.
AB  - OBJECTIVE: To evaluate, in a prospective study, the combination of the
      antimuscarinic propiverine and the antidiuretic hormone-agonist desmopressin in
      children and adolescents not responsive to previous monotherapy, as in primary
      monosymptomatic enuresis (PME), combined treatments are considered a second-line
      approach after the failure of monotherapy. PATIENTS AND METHODS: The study
      included 122 children and adolescents (mean age 10.8 years, range 5-21) with PME
      and so far unresponsive to single or multiple monotherapy. Propiverine (body
      weight <30 kg, 15 mg/day; >or=30 kg, 20 mg/day) and desmopressin (0.4 mg/night)
      were administered over 3 months, followed by successive structured withdrawal
      programmes for propiverine and desmopressin, depending on the amount of loss of
      urine at night before treatment. RESULTS: The re-evaluation of unresponsive
      patients, incorporating video-urodynamics, showed neurogenic detrusor
      overactivity, isolated detrusor sphincter dyssynergia and vesicorenal reflux in
      12.3% (15/122) of patients, so far falsely treated as enuresis. In 107 of 122
      patients the diagnosis of PME was confirmed. The primary efficacy outcome,
      continence at night, was achieved in 104 of 107 patients (97.2%). During the
      individual follow-up periods (3-12 months), 23 of 107 (21.5%) patients relapsed
      after withdrawal of both medications. Adverse events of moderate intensity were
      rare (3.7%). CONCLUSION: Re-evaluation of patients after monotherapy has failed
      is justified, because other entities can be discovered in patients so far treated
      unsuccessfully for enuresis. The combination of propiverine and desmopressin is
      highly effective in children with PME. Our results support the case for further
      optimizing the inaugurated treatment algorithm of PME for treatment duration,
      dose-titration and structured withdrawal programmes, thus possibly further
      decreasing relapse rates.

PMID- 19154457
TI  - Laser treatment of benign prostatic hyperplasia in patients on oral anticoagulant
      therapy: a review.
AB  - We assessed the therapeutic efficacy and safety of laser prostatectomy (LP) for
      treating benign prostatic hyperplasia (BPH) in patients on oral anticoagulation.
      We systematically reviewed previous reports, using the Pubmed database and
      bibliographies of retrieved articles and reviews. The oral anticoagulation
      included coumarin derivatives and platelet-aggregation inhibitors (PAI). Previous
      studies do not allow the establishment of definitive conclusions for managing
      patients on oral anticoagulation and who require BPH surgery. No randomized
      studies are available. Nevertheless, compared to transurethral resection of the
      prostate (TURP), LP seems to decrease the risk of haemorrhage in patients taking
      PAI or coumarin derivatives. Therefore, LP is a useful alternative to TURP for
      managing patients on oral anticoagulation, and could be proposed as the first
      intention for those patients. Continuing PAI during the procedure is feasible. A
      replacement of coumarin derivatives by low molecular weight heparin is
      preferable. No conclusion can be reached on the preferred type of laser technique
      to treat these patients, but data on laser enucleation is much less abundant and
      conclusive than that on laser vaporization.

PMID- 19154459
TI  - Bacille-Calmette Guerin induces caspase-independent cell death in urothelial
      carcinoma cells together with release of the necrosis-associated chemokine high
      molecular group box protein 1.
AB  - OBJECTIVE: To evaluate the ability of bacille-Calmette Guerin (BCG) to induce
      caspase-independent cell death and release the necrosis-associated chemokine high
      molecular group box protein 1 (HMGB1) from urothelial carcinoma (UC) cells; a
      correlative clinical trial determined if BCG treatment resulted in increased
      urinary levels of HMGB1. PATIENTS, MATERIALS AND METHODS: The human UC cell lines
      253 J and T24 were pretreated with apoptosis inhibitors, exposed to BCG, and cell
      viability and ultrastructural changes measured. HMGB1 levels were assessed in
      cell culture supernatant after BCG treatment. The expression/function of HMGB1
      receptors on the UC cell lines was determined by reverse transcription-polymer
      chain reaction and the ability of exogenous HMGB1 to activate nuclear factor (NF)
      kappaB signalling assessed. An HMGB1 enzyme-linked immunosorbent assay was used
      to measure HMGB1 levels in urine obtained from BCG-treated patients. RESULTS:
      Inhibition of apoptotic pathways failed to inhibit BCG-induced cell death in UC
      cells. Electron microscopy showed BCG-dependent ultrastructural changes
      consistent with cellular necrosis. BCG exposure resulted in a binary increase in
      cell culture supernatant levels of HMGB1. UCs expressed multiple HMGB1 receptors.
      Treatment of UCs with HMGB1 activated NF-kappaB. In the clinical setting, six of
      seven patients had increased urinary levels of HMGB1 at 24 h after BCG treatment.
      CONCLUSIONS: BCG causes direct cytotoxicity in a subpopulation of UC cells. This
      cytotoxicity is caspase-independent and associated with ultrastructural changes
      and cellular protein release (HMGB1), characteristic of necrosis. Urinary levels
      of HMGB1 can be elevated in patients after BCG treatment. The expression and
      function of HMGB1 receptors in UC cells, coupled with the known role of HMGB1 on
      the host immune response, suggest a role for necrosis and HMGB1 release in the
      antitumour effect of BCG.

PMID- 19154458
TI  - Pretreatment with low-energy shock waves induces renal vasoconstriction during
      standard shock wave lithotripsy (SWL): a treatment protocol known to reduce SWL
      induced renal injury.
AB  - OBJECTIVE: To test the hypothesis that the pretreatment of the kidney with low
      energy shock waves (SWs) will induce renal vasoconstriction sooner than a
      standard clinical dose of high-energy SWs, thus providing a potential mechanism
      by which the pretreatment SW lithotripsy (SWL) protocol reduces tissue injury.
      MATERIALS AND METHODS: Female farm pigs (6-weeks-old) were anaesthetized with
      isoflurane and the lower pole of the right kidney treated with SWs using a
      conventional electrohydraulic lithotripter (HM3, Dornier GmbH, Germany). Pulsed
      Doppler ultrasonography was used to measure renal resistive index (RI) in blood
      vessels as a measure of resistance/impedance to blood flow. RI was recorded from
      one intralobar artery located in the targeted pole of the kidney, and
      measurements taken from pigs given sham SW treatment (Group 1; no SWs, four
      pigs), a standard clinical dose of high-energy SWs (Group 2; 2000 SWs, 24 kV, 120
      SWs/min, seven pigs), low-energy SW pretreatment followed by high-energy SWL
      (Group 3; 500 SWs, 12 kV, 120 SWs/min + 2000 SWs, 24 kV, 120 SWs/min, eight pigs)
      and low-energy SW pretreatment alone (Group 4; 500 SWs, 12 kV, 120 SWs/min, six
      pigs). RESULTS: Baseline RI (approximately 0.61) was similar for all groups. Pigs
      receiving sham SW treatment (Group 1) had no significant change in RI. A standard
      clinical dose of high-energy SWs (Group 2) did not significantly alter RI during
      treatment, but did increase RI at 45 min after SWL. Low-energy SWs did not alter
      RI in Group 3 pigs, but subsequent treatment with a standard clinical dose of
      high-energy SWs resulted in a significantly earlier (at 1000 SWs) and greater
      (two-fold) rise in RI than that in Group 2 pigs. This rise in RI during the
      low/high-energy SWL protocol was not due to a delayed vasoconstrictor response of
      pretreatment, as low-energy SW treatment alone (Group 4) did not increase RI
      until 65 min after SWL. CONCLUSIONS: The pretreatment protocol induces renal
      vasoconstriction during the period of SW application whereas the standard
      protocol shows vasoconstriction occurring after SWL. Thus, the earlier and
      greater rise in RI during the pretreatment protocol may be causally associated
      with a reduction in tissue injury.

PMID- 19154460
TI  - The impact of training on service provision in laparoscopic radical
      prostatectomy.
AB  - OBJECTIVE: To address concerns about the impact of training on patient outcomes
      during the 'learning curve' for laparoscopic radical prostatectomy (LRP), we
      compare the results of our patients undergoing LRP with and without trainees
      performing a substantial proportion of the cases. PATIENTS AND METHODS: In all,
      771 consecutive cases of LRP were performed or supervised by one surgeon during a
      7.5-year period, of which 114 (15%) were training cases. A five-port
      transperitoneal technique was used in the first 111 patients and an
      extraperitoneal approach in the remaining 660. Patient, operative and oncological
      outcome variables were compared using an independent samples t-test if continuous
      or with Fisher's exact test for rates. RESULTS: There were no differences in
      preoperative patient or cancer characteristics with the exception of body mass
      index (BMI) which was lower in the training cases (medians 25 and 26 kg/m(2), P =
      0.02) and patient age which was higher (medians 64 and 62 years, P < 0.001).
      Operative time, which was longer in training cases (medians 200 and 175 min, P <
      0.001) was the only significantly different operative variable between the
      groups. There were no statistically significant differences in postoperative
      (duration of catheterization, hospitalization time, complication rates,
      biochemical recurrence and pad-free rates at 1 year) or pathological (gland
      weight, positive surgical margin rate) outcomes between the groups. As Fellows
      did not perform the posterior or apical dissection steps in nerve-sparing cases,
      no evaluation of potency outcomes is included. CONCLUSIONS: Training cases took a
      median of 25 min longer to complete than non-training cases. However, other
      perioperative measures, complications rates and cancer outcomes were similar.
      Adequately supervised training in LRP does indeed take additional time but is
      essential for the dissemination of surgical skills and preservation of acceptable
      outcomes.

PMID- 19154461
TI  - Concordance between Gleason scores of needle biopsies and radical prostatectomy
      specimens: a population-based study.
AB  - OBJECTIVE: To study the concordance between the Gleason scores of needle biopsies
      and radical prostatectomy (RP) specimens in a population-based registry, to
      clarify whether the concordance depends on the annual number of RP specimens
      assessed in the pathology unit, and to identify preoperative clinical factors
      that predict upgrading from a Gleason score of <or=6 in the biopsy to >or=7 in
      the RP specimen. PATIENTS AND METHODS: Through the Cancer Registry of Norway, we
      identified 1116 patients with available Gleason scores from biopsy and RP
      specimens. Concordance was evaluated using the kappa coefficient, and predictors
      of concordance were assessed in univariate and multivariate logistic regression
      analyses. RESULTS: The Gleason scores were identical in biopsy and RP specimens
      in 591 of the 1116 (53%) patients. The biopsy-based Gleason score more often
      under-graded (38%) than over-graded (9%) the RP-based Gleason score. Pathology
      units that examined >40 RP specimens annually had a higher concordance between
      the Gleason score in the biopsy and RP specimen than did lower-volume units. The
      rate of upgrading from a Gleason score of <or=6 in the biopsy to >or=7 in the RP
      specimen increased with increasing preoperative prostate-specific antigen serum
      levels, and with increasing intervals between biopsy and RP. CONCLUSIONS: The
      concordance in Gleason score between biopsy and RP was highest among the
      pathology departments that regularly evaluated RP specimens. Careful
      consideration of clinical factors and biopsy grading might improve the
      identification of patients considered as suitable for active surveillance.

PMID- 19154462
TI  - Src as a therapeutic target in men with prostate cancer and bone metastases.
AB  - While responsive to androgen ablation in its early stages, prostate cancer
      eventually becomes castration-resistant and metastasizes preferentially to bone.
      Once this happens, the disease carries considerable morbidity and is incurable.
      The process of bone metastasis involves a complex interplay between tumour and
      bone tissue. The eventual characteristic clinical presentation of disorganized
      osteoblastic bone lesions is preceded by a facilitatory osteoblastic phase; an
      osteoblastic component then continues to underlie the process. Increasing
      evidence has shown a ubiquitous role for Src (a proto-oncogene tyrosine-protein
      kinase) in multiple tumour and bone-signalling processes involved in prostate
      tumour progression, driving proliferation, survival, migration and transition to
      androgen-independent growth. It is also intimately involved in positively
      regulating osteoclast physiology. As such, this molecule represents an attractive
      target for managing progressing prostate cancer. Encouraging results have been
      obtained in preclinical and clinical studies using Src inhibitors like AZD0530
      and dasatinib. Both compounds reduced markers of bone resorption, in patients
      with cancer and those with advanced castration-resistant prostate cancer,
      respectively. Moreover, because Src is central to many mechanisms thought to be
      responsible for the development of castration resistance, adding Src inhibitors
      to a treatment regimen might reverse this phenomenon. As a result, many Src
      inhibitors are in preclinical development. This review explores Src inhibition as
      a strategy for managing bone metastasis in prostate cancer, with a particular
      focus on targeting the critical osteoclastic response. Other emerging and novel
      approaches are also considered.

PMID- 19154463
TI  - Clinical staging error in prostate cancer: localization and relevance of
      undetected tumour areas.
AB  - OBJECTIVE: To describe the localization and to assess the clinical implications
      of areas of undetected prostate cancer in radical prostatectomy (RP) specimens,
      focusing on patients with unilaterally negative preoperative biopsy cores.
      PATIENTS AND METHODS: The study included 149 of 559 consecutive patients (26.7%)
      who had RP for prostate cancer. Unilateral prostate cancer was diagnosed from
      prostate biopsies, taken by several physicians, but > or = pT2c disease was
      present in the RP specimen. The prostate was dissected by standardized
      transversal cuts and tumour areas were mapped by one genitourinary pathologist.
      To estimate the tumour size and location, areas of prostate cancer were
      transferred to a digital grid database representing the prostate by 794 units.
      RESULTS: The most frequent location of undetected prostate cancer was in the
      dorsalateral region and in the apex of the prostate. The mean tumour volume of
      the false-negative lobe was significantly lower than contralaterally (18.9 vs
      47.5 units, P < 0.001). In 36 of 149 patients (24.2%), the tumour volume on the
      negative biopsy side was equal or higher than on the positive biopsy side; in the
      final RP specimen, 60 patients (40.3%) had capsular involvement on the negative
      biopsy side. CONCLUSION: Significantly many patients with newly diagnosed
      prostate cancer remain clinically understaged. The apical and dorsolateral region
      of the prostate are not adequately represented in current biopsy strategies.
      Undetected tumour areas are often clinically significant by size and capsular
      involvement, indicating a direct clinical implication when planning nerve-sparing
      RP or focal therapy. Our results show a continuing need for optimized and
      standardized biopsy protocols.

PMID- 19154464
TI  - Invasion of renal sinus fat is not an independent predictor of survival in pT3a
      renal cell carcinoma.
AB  - OBJECTIVE: To clarify the significance of the location of extrarenal tumour
      extension of renal cell carcinoma (RCC) as in the 2002 Tumour-Nodes-Metastasis
      classification. Renal cortical tumours with perirenal fat invasion (PFI) or sinus
      fat invasion (SFI) are consolidated within the pT3a grouping; tumours with SFI
      are close to the renal veins, lymphatics and the collecting system. This might
      carry a worse prognosis for disease-specific survival (DSS), but reports are
      limited and contradictory. PATIENTS AND METHODS: We retrospectively reviewed 1244
      patients treated with nephrectomy from 1988 to 2007, to identify patients with
      pT3a renal tumours. They were classified as having PFI or SFI. Kaplan-Meier
      analysis and Cox proportional hazards regression models were used to assess
      predictors of survival. RESULTS: The 230 patients who met the inclusion criteria
      had a median follow-up of 24 months. SFI was found in 63 (27.4%) patients and was
      associated with a worse 5-year DSS than the 167 (72.6%) with PFI (62.5% vs 75.0%;
      log rank P = 0.022). On univariate analysis, diameter (hazard ratio, HR 1.1),
      nuclear grade (HR 4.5), margin status (HR 5.8), lymph node metastases (HR 6.4),
      and systemic metastases (HR 15.4) were significant for DSS. In a multivariate
      model, only nuclear grade (HR 3.1), margin status (HR 8.9) and systemic
      metastases (HR 9.8) were independent predictors. CONCLUSION: Patients with renal
      tumours with SFI are more likely to die from RCC than those with PFI. However, in
      the present patients the presence of SFI was not an independent predictor of DSS.

PMID- 19154465
TI  - Mentorship in urological laparoscopic surgery: lessons learned.
AB  - OBJECTIVE: To review the results of our experience with a mentorship programme in
      laparoscopic nephrectomy, set up in 1999 by the British Association of Urological
      Surgeons Section of Endourology. METHODS: Mentors were contacted in 2007 to
      submit data on the number of visits and the outcome, which included whether a
      urologist was able to establish an independent laparoscopic practice and sustain
      it. RESULTS: Four urologists acting as mentors reported a total of 164 procedures
      carried out in the training of 39 urologists during 148 visits. There were no
      conversions to open surgery and only one major complication. Overall, 29 of 39
      mentored consultants were able to establish an independent laparoscopic practice
      and 23 continue to do so. The number of visits was associated with initial
      success, although this was not statistically significant. Working in a large
      department was associated with being able to sustain a laparoscopic practice.
      More experienced consultants were less likely to have initial success, but were
      more likely to sustain a successful practice. CONCLUSIONS: Mentorship for
      laparoscopic nephrectomy has been carried out safely thus far. Sustaining a
      laparoscopic practice requires a critical volume of cases. Future efforts should
      be focused on trainees rather than consultants.

PMID- 19154466
TI  - The effect of sildenafil citrate on bladder outlet obstruction: a mouse model.
AB  - OBJECTIVE: To investigate if sildenafil citrate can inhibit the functional and
      structural changes of the detrusor in a murine model of bladder outlet
      obstruction (BOO). Phosphodiesterase type 5 (PDE-5) inhibitors have recently been
      used for treating urinary symptoms associated with prostatic obstruction, but it
      is unclear whether PDE-5 inhibition acts on the prostatic urethra or the bladder.
      MATERIALS AND METHODS: In 18 male Balb/CAN mice, partial BOO was created and the
      mice allowed to survive for 6 weeks. Half of the mice (nine) were treated with
      oral sildenafil citrate daily (10 mg/kg) by oral lavage (BOO + V), and half
      (nine) were not (BOO). Six mice were used as sham-operated controls and received
      no sildenafil. The mice were assessed by urodynamics at baseline and after 6
      weeks, with a measurement of volume at first uninhibited non-voiding contraction
      (V(DO1)), bladder capacity (BC), and detrusor pressure during void (Pdet). At 6
      weeks, bladders were harvested, fixed and sectioned, and stained with
      haematoxylin and eosin (H&E) and trichrome stain. Detrusor muscle hypertrophy and
      fibrosis were evaluated on a scale of 1 (decreased) to 3 (increased), by two
      urologists and one pathologist unaware of the treatment group; the results were
      compared with those from normal controls. RESULTS: BOO mice had a significantly
      greater BC than control mice, with a mean (SD) of 153 (66) vs 58 (13) microL (P =
      0.004). Treatment with sildenafil did not significantly alter BC. BOO caused an
      increase in Pdet compared to controls, with a mean (SD) of 25 (7) vs 12 (5) cm
      H2O. P(det) was not significantly different after treatment with sildenafil. The
      median V(DO1) as a percentage of BC was significantly lower in BOO than in
      control mice (20% vs 53%, P > 0.03) and increased significantly after sildenafil
      treatment (20% vs 44%, P = 0.04). BOO was associated with a greater bladder
      weight than in control mice, with a mean (SD) of 89 (32) vs 27 (6) mg (P =
      0.001), which was decreased with sildenafil treatment, to 40 (14) vs 89 (32) mg
      (P = 0.013). BOO caused an increase in detrusor muscular hypertrophy vs control
      mice, with a median H&E score of 3 vs 2 (P = 0.01) and an increase in fibrosis vs
      control mice, with a median trichrome score of 3 vs 2 (P = 0.01). BOO + V mice
      had reduced muscular hypertrophy and fibrosis, with a median H&E score of 3 vs 2
      (P = 0.01) and a median trichrome score of 3 vs 1 (P = 0.01). CONCLUSIONS: BOO
      mediates both functional and structural changes in the mouse bladder. Six weeks
      of obstruction caused an increase in BC, detrusor overactivity and voiding
      pressure, and mediated an increase in bladder weight, detrusor muscle hypertrophy
      and collagen deposition in the lamina propria and smooth muscle. Treatment with 6
      weeks of oral sildenafil beginning at the time of BOO prevented the increase in
      detrusor overactivity without affecting voiding pressures, and prevented the
      increase in detrusor muscle hypertrophy and collagen deposition that otherwise
      occurred with BOO. It appears therefore that sildenafil citrate acts on the
      bladder rather than on the outlet.

PMID- 19154467
TI  - A low frequency of lymph node metastasis in clear-cell renal cell carcinoma is
      related to low lymphangiogenic activity.
AB  - OBJECTIVE: To assess ongoing lymphangiogenesis in renal cell carcinoma (RCC) by
      histomorphometry and by quantifying mRNA expression levels of lymphangiogenesis
      related factors. MATERIALS AND METHODS: Using D2-40 antibody as a lymphatic
      marker, lymph vessels were counted in tissue sections of 150 clear-cell RCCs
      (ccRCC) and 61 non-neoplastic controls, using the Chalkley method, which measures
      the relative lymph vessel area (LVA). Double-staining with Ki67 and D2-40 was
      used to assess active lymphangiogenesis. In a subset of 25 ccRCCs and nine non
      neoplastic controls mRNA expression levels of lymphangiogenic factors were
      determined by real-time quantitative reverse transcription-polymerase chain
      reaction. RESULTS: LVA was higher in normal renal tissue than in both intra- and
      peri-tumoral LVA (P < 0.001). LVA in the tumour periphery was higher than in the
      tumour parenchyma (P < 0.001). Lymphatic endothelial cell proliferation (LECP)
      was identified in 8.2% of the control sections and was higher than the
      intratumoral LECP fraction (LECP%, 2.6%; P = 0.02) and the peritumoral LECP%
      (6.5%; P > 0.05). Compared with controls, ccRCC specimens had higher mRNA
      expression levels of vascular endothelial growth factor (VEGF)-A and VEGF-C, but
      lower expression levels of VEGF-D and Prox-1 (all P < 0.001). CONCLUSION: Our
      results show that there is only limited ongoing lymphangiogenesis in ccRCC. Given
      that several growth factors stimulate both angiogenesis and lymphangiogenesis,
      our observation indirectly indicates that haemangiogenesis predominates in ccRCC.
      This finding might provide better understanding of why ccRCCs prefer
      haematogenous dissemination to lymphatic spread.

PMID- 19154468
TI  - Serenoa repens extract targets mitochondria and activates the intrinsic apoptotic
      pathway in human prostate cancer cells.
AB  - OBJECTIVE: To investigate the effects of Serenoa repens extract (Sr) in human PC3
      and LNCaP prostate cancer and MCF7 breast cancer cells, with specific emphasis on
      the role of the mitochondrial apoptotic pathway, as the molecular pathway through
      which Sr, a natural product of plant origin, induces death of prostate cancer
      cells in culture is still unknown. MATERIAL AND METHODS: Cellular and
      mitochondrial structure and function, and the cell cycle, were analysed using
      light, electron and fluorescence microscopy, spectrophotometry and flow
      cytometry. Apoptosis was evaluated using biochemical and cytohistochemical
      methods. RESULTS: Cells treated with Sr underwent massive vacuolization and
      cytosolic condensation, followed by cell death only in the prostate lines. Within
      minutes of adding Sr to prostate cells, it caused opening of the permeability
      transition pore (PTP), which led to complete mitochondrial depolarization within
      2 h, and to the appearance of small, pycnotic mitochondria. Release of cytochrome
      c and SMAC/Diablo to the cytosol was detectable after 4 h of treatment, while
      caspase 9 activation and poly(ADP-ribose) polymerase 1 cleavage occurred at 16 h,
      followed by appearance of a sub-G1 peak and apoptosis at 24 h. CONCLUSION: Sr
      selectively induces apoptotic cell death of prostate cancer cells through the
      intrinsic pathway, and activation of the mitochondrial PTP might play a central
      role in this process.

PMID- 19154469
TI  - The 'buoy' stent: evaluation of a prototype indwelling ureteric stent in a
      porcine model.
AB  - OBJECTIVE To assess a prototype ureteric 'buoy' stent with a 10 F upper body
      tapering to a 3F tail, developed to potentially reduce stent-related irritative
      symptoms while providing an adequate mould for healing after endopyelotomy.
      MATERIALS AND METHODS Eighteen Yucatan minipigs had the stent placed either into
      the intact ureter (phase I) or after Acucise proximal endoureterotomy (phase II).
      Buoy stents were compared to 10/7 F endopyelotomy stents and to standard 7 F
      stents in phases I and II, respectively. The pigs were assessed for vesico
      ureteric reflux, hydronephrosis and infection, before stent insertion and at
      harvest. Stents were weighed before and after placement and the removal force was
      measured. Pressure/flow studies, antegrade nephrostograms and specimens for
      histopathology from the renal pelvis, ureter and vesico-ureteric junction (VUJ)
      were obtained at harvest. RESULTS Thirteen minipigs survived the entire study.
      Ureteric flow with the stents in situ was better for buoy stents than for 10/7 F
      stents (P < 0.005). Ureteric flow after endoureterotomy and subsequent stent
      removal was similar for buoy stents and standard 7 F stents. None of the stents
      refluxed. There was no difference between stents in removal force, weight change
      or incidence of hydronephrosis. At 1 and 12 weeks, buoy stents tended to produce
      lower histopathological alteration scores than control stents, especially at the
      VUJ (phase I, 2.0 vs 3.9, P = 0.092; phase II, 0.6 vs 1.7, P = 0.18). CONCLUSIONS
      The novel buoy stents are easily placed and removed via the urethra. They can
      cause less VUJ inflammation than standard stents while allowing for adequate
      ureteric flow and healing after proximal endoureterotomy.

PMID- 19154470
TI  - Effects of ageing and streptozotocin-induced diabetes on connexin43 and P2
      purinoceptor expression in the rat corpora cavernosa and urinary bladder.
AB  - OBJECTIVE: To investigate whether ageing and diabetes alter the expression of the
      gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R)
      subtypes in the corpus cavernosum and urinary bladder, and determine whether
      changes in expression of these proteins correlate with development of erectile
      and bladder dysfunction in diabetic and ageing rats. MATERIALS AND METHODS:
      Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin
      treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months
      after diabetes induction by in vivo cystometry and cavernosometry. Corporal and
      bladder tissue were then isolated at each of these sample times and protein
      expression levels of Cx43 and of various P2R subtypes were determined by Western
      blotting. RESULTS: In the corpora of control rats ageing was accompanied by a
      significant decrease in Cx43 and P2X(1)R, and increase in P2X(7)R expression.
      There was decreased Cx43 and increased P2Y(4)R expression in the ageing control
      rat bladder. There was a significant negative correlation between erectile
      capacity and P2X(1)R expression levels, and a positive correlation between
      bladder spontaneous activity and P2Y(4)R expression levels. There was already
      development of erectile dysfunction and bladder overactivity at 2 months after
      inducing diabetes, the earliest sample measured in the study. The development of
      these urogenital complications was accompanied by significant decreases in Cx43,
      P2Y(2)R, P2X(4)R and increase in P2X(1)R expression in the corpora, and by a
      doubling in Cx43 and P2Y(2)R, and significant increase in P2Y(4)R expression in
      the bladder. Changes in Cx43 and P2R expression were largely prevented by insulin
      therapy. CONCLUSION: Ageing and diabetes mellitus markedly altered the expression
      of the gap junction protein Cx43 and of particular P2R subtypes in the rat penile
      corpora and urinary bladder. These changes in Cx43 and P2R expression provide the
      molecular substrate for altered gap junction and purinergic signalling in these
      tissues, and thus probably contribute to the early development of erectile
      dysfunction and higher detrusor activity in ageing and in diabetic rats.

PMID- 19154471
TI  - The medical management of metastatic renal cell carcinoma: integrating new
      guidelines and recommendations.
AB  - There are now five targeted agents, i.e. sorafenib, sunitinib, temsirolimus,
      bevacizumab (in combination with interferon) and everolimus, that have been shown
      to improve the outcome in patients with metastatic clear cell renal cell
      carcinoma (mRCC), in randomized controlled trials (RCTs). Compared with the
      period when cytokines were the only systemic intervention known to have any
      activity, decisions on medical management are now complex. Clinicians must seek
      to adjust therapy to the circumstances of the individual patient, and consider
      the sequencing of agents. In this context, several expert groups have sought to
      provide treatment guidelines. As in other diseases, guidelines for mRCC seek to
      establish evidence-based recommendations for best clinical practice and to
      encourage their widespread use. Data from phase III trials (level 1 evidence) are
      an essential element in this process, and guidelines need continual updating in
      the light of new findings. However, there are inevitably questions that large
      RCTs have not directly addressed. This is the case for major subgroups of the
      mRCC population, e.g. the elderly and those with comorbidities. In these
      circumstances, less well-controlled sources of data, and clinical experience,
      have a role to play. Certain guidelines (although not all) acknowledge the
      contribution that such sources of evidence can make.

PMID- 19154472
TI  - Urological symptom clusters and health-related quality-of-life: results from the
      Boston Area Community Health Survey.
AB  - OBJECTIVE To determine whether urological symptom clusters, as identified in
      previous studies, were associated with health-related quality-of-life (HRQoL) and
      use of healthcare. SUBJECTS AND METHODS The Boston Area Community Health Survey
      is a population-based epidemiological study of 2301 male and 3201 female
      residents of Boston, MA, USA, aged 30-79 years. Baseline data collected from 2002
      to 2005 were used in this analysis. Data on 14 urological symptoms were used for
      the cluster analysis, and five derived symptom clusters among men and four among
      women were used in multivariate linear regression models (adjusted for age group,
      race/ethnicity, and comorbidity) to determine their association with physical
      (PCS-12) and mental health component scores (MCS-12) calculated from the Medical
      Outcomes Study 12-item Short Form Survey. RESULTS For both men and women, being
      in the most symptomatic cluster was associated with decrements in the PCS-12
      score (men, cluster 5, -10.42; women, cluster 4, -9.80; both P < 0.001) and the
      MCS-12 score (men, cluster 5, -9.35; women, cluster 4, -6.24; both P < 0.001)
      compared with the asymptomatic groups. Both men and women in these most
      symptomatic clusters appeared to have adequate access to healthcare. CONCLUSION
      For men and women, those with the most urological symptoms reported poorer HRQoL
      in two domains after adjusting for age and comorbidity, and despite adequate
      access to care.

PMID- 19154473
TI  - Sexual function of patients under surveillance for bladder cancer.
AB  - OBJECTIVE To describe the prevalence of sexual dysfunction and evaluate risk
      factors in patients just diagnosed with non-muscle-invasive bladder cancer (NMI
      UC), who have the prospect of an intensive surveillance scheme by cysto
      urethroscopy to detect tumour recurrences. PATIENTS AND METHODS We conducted a
      cross-sectional survey on 150 patients just diagnosed with primary or recurrent
      NMI UC. Patients were participating in a randomized clinical multicentre trial
      (CEFuB), comparing two surveillance schemes. Patients were asked to complete
      questionnaires at study entry 3 months before the start of the study-surveillance
      scheme (demographic characteristics, a validated visual analogue scale, and
      validated subset of questions on sexual function and performance derived from QLQ
      BLS-24). The results were compared with those from an age-and gender-matched
      healthy population. RESULTS The response rate was 95% (142/150); 61% (87/142) of
      the respondents were sexually active in the previous 4 weeks after diagnosis, 66%
      (70/105) of men and 46% (17/37) of women. Although libido was not negatively
      affected, 54% (47/87) of the patients had a sexual dysfunction, and 23% (17/73)
      were afraid to inflict harm on their partner by sexual contact. Sexually active
      patients perceived a higher state of general health (P = 0.03). CONCLUSIONS The
      prevalence of sexual dysfunction in patients with NMI UC is very high (54%)
      compared with an age- and gender-matched healthy population (20-45%). No
      predictors for sexual dysfunction were found. These patients and partners would
      benefit from proper sexual information in the outpatient clinic.

PMID- 19154474
TI  - A double-blind randomized controlled trial of electromagnetic stimulation of the
      pelvic floor vs sham therapy in the treatment of women with stress urinary
      incontinence.
AB  - OBJECTIVE: To compare the efficacy of extracorporeal electromagnetic stimulation
      (ES) of the pelvic floor for treating stress urinary incontinence (SUI) vs sham
      ES. PATIENTS AND METHODS: In all, 70 women with urodynamically confirmed SUI were
      randomized to receive active (35) or sham (35) ES. The NeoControl chair
      (NeoTonus, Marietta, GA, USA) was used, and treatment consisted of three sessions
      per week for 6 weeks. data were collected before and after treatment on all
      women, including a 20-min provocative pad-test with a predetermined bladder
      volume (primary outcome measure), a 3-day bladder diary and 24 h pad-test.
      Circumvaginal muscle (CVM) rating score, perineometry using two separate
      instruments and video-urodynamics were also used, and the Urinary Incontinence
      Quality of Life Scale (I-QOL) and King's Health Questionnaires. Patients were
      fully re-evaluated 8 weeks after treatment, and the bladder diary, pad-test and
      questionnaires were repeated at 6 months. The urotherapist and physician were
      unaware to which treatment group the patient was assigned. RESULTS: In the
      overall group of 70 patients there were significant improvements in each of the
      primary and secondary outcome measures at 8 weeks. There were also significant
      improvements in primary and secondary outcome measures in the active treatment
      group when compared with baseline measures. At 8 weeks, there were improvements
      in the mean (sd) values for the 20-min pad-test, of 39.5 (5.1) vs 19.4 (4.6) g (P
      < 0.001); the 24-h pad-test, of 24.0 (4.7) vs 10.1 (3.1) g (P < 0.01); the number
      of pads/day, of 0.9 (0.1) vs 0.6 (0.1) (P < 0.01), the I-QOL score, of 63.7 (2.8)
      vs 71.2 (3.3) (P < 0.001); and King's Health Questionnaire score, of 9.6 (0.8) vs
      6.9 (0.7) (P < 0.001). However, these improvements were not statistically
      significant when compared with the sham-treatment group. In those patients on
      active treatment who had a poor pelvic floor contraction at the initial
      assessment (defined by the CVM score and perineometry), there was a significant
      reduction (P < 0.05) in the 20-min pad-test leakage when compared with the sham
      treatment group. CONCLUSIONS: ES was no more effective overall than sham
      treatment in this patient group. However, in those women who were unable to
      generate adequate pelvic floor muscle contractions, there was an objective
      improvement in provocative pad testing when compared to sham treatment.

PMID- 19154475
TI  - The role of magnetic resonance imaging in targeting prostate cancer in patients
      with previous negative biopsies and elevated prostate-specific antigen levels.
AB  - In the past 20 years, magnetic resonance imaging (MRI) has developed rapidly,
      along with the management of localized prostate cancer. We summarize current data
      on the efficacy of MRI for targeting cancer, compared with biopsies, in patients
      with previous negative prostate biopsies and persistently elevated prostate
      specific antigen (PSA) levels. The key clinical question is how many men benefit
      by having had prostate cancer detected purely because of the MRI-targeted, as
      opposed to standard scheme, biopsies. We reviewed all available databases for
      prospective studies in patients having MRI and prostate biopsy with previous
      negative biopsies and persistently elevated PSA levels. Six studies fulfilled the
      selection criteria, with 215 patients in all; in these studies, the cancer
      detection rate at repeat biopsy was 21-40%. For MRI or combined MRI/MR
      spectroscopy, the overall sensitivity for predicting positive biopsies was 57
      100%, the specificity 44-96% and the accuracy 67-85%. In five studies, specific
      MRI-targeted biopsies and standard cores were taken, with a significant
      proportion (34/63, 54%) having cancer detected purely because of the MRI-targeted
      cores. The value of endorectal MRI and MR spectroscopy in patients with elevated
      PSA levels and previous negative biopsies to target peripheral zone tumours
      appears to be significant. Although more data obtained with current technologies
      are needed, published results to data are encouraging. A comparison study and
      cost-benefit analysis of MRI-targeted vs saturation biopsy in this group of
      patients would also be ideal, to delineate any advantages.

PMID- 19154476
TI  - The haphazard approach to the early detection of asymptomatic renal cancer:
      results from a contemporary executive health programme.
AB  - OBJECTIVE To compare the detection of asymptomatic renal cell carcinoma (RCC) in
      an executive health programme (EHP) that uses traditional methods of screening
      (history, physical examination and urine analysis) to programmes that screen by
      renal imaging. PATIENTS AND METHODS We retrospectively reviewed case records from
      patients undergoing executive health examinations at Mayo Clinic between 1
      January 2002 and 30 September 2007. Results Of 32 310 patients, 18 RCCs were
      detected; of these, 13 (72%) were detected by the EHP and five (28%) were missed
      by the initial EHP screening process but subsequently discovered within 4-24
      months. Of the 13 detected through the EHP, eight were discovered incidentally,
      two because of symptoms, and three because of asymptomatic microscopic haematuria
      (AMH). Of the 13, 12 were classified as early-stage cancers (Stage I). By
      contrast, of the five cancers missed by the EHP screening process, two were
      diagnosed because of the development of symptoms and only one was classified as
      Stage I. To date, two of these patients whose cancers were undetected by the EHP
      developed metastasis and one of them has died. Both had been followed in the EHP
      for years and neither had MH in multiple specimens. CONCLUSION Our EHP follows
      standard policy and relies on a history, physical examination and urine analysis
      to decide who to evaluate for asymptomatic RCC. This practice missed >70% of the
      potentially diagnosable cancers. The patients with RCCs that were discovered
      initially by the EHP fared better than those whose diagnosis was delayed. Our
      detection rate of four per 10 000 was only a fraction of those reported by
      programmes using imaging as a screening tool. The logic behind our current
      approach to the early detection of asymptomatic RCC needs to be reassessed. AMH
      is coincidental in most cases and patients could forego imaging if they are
      unsuitable candidates for screening. However, AMH will miss most treatable
      cancers and is not an appropriate screening test for an early detection
      programme. In the absence of reliable biomarkers, renal imaging should be the
      primary screening tool for detecting asymptomatic RCC in informed, clinically
      suitable individuals enrolled in an early detection programme.

PMID- 19154477
TI  - Screening by lower urinary tract symptoms vs asymptomatic prostate-specific
      antigen levels leading to radical prostatectomy in Danish men: tumour
      characteristics and treatment outcome.
AB  - OBJECTIVE: To compare the tumour characteristics and treatment outcome in men
      undergoing radical prostatectomy (RP) for prostate cancer diagnosed with or with
      no lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: In Denmark,
      prostate-specific antigen (PSA) testing is recommended only in men with a family
      history of prostate cancer, or those with LUTS that could be caused by prostate
      cancer. However, increasingly many men undergoing RP are asymptomatic and are
      diagnosed as a result of unsystematic PSA screening. Data were collected
      prospectively from The Aarhus PC-project, comprising 585 consecutive Danish men
      treated with RP between 1997 and 2008 at Aarhus University Hospital; of these, 47
      had a family history of prostate cancer and were therefore excluded. RESULTS: In
      all, 188 (35%) patients stated being asymptomatic at the diagnosis of cancer,
      while LUTS led to the diagnosis in 350 (65%). Except for tumour grade after RP
      there were no significant differences between these subpopulations in tumour
      characteristics and treatment outcome. Unexpectedly, the Gleason score of the RP
      specimen was a statistically significant prognostic indicator (P = 0.002) in
      favour of symptomatic patients. CONCLUSION: This study showed no association
      between LUTS and tumour characteristics or treatment outcome between symptomatic
      and asymptomatic patients undergoing RP. The Gleason score at RP and thereby the
      long-term prognosis in asymptomatic patients seems to be worse than in patients
      with LUTS.

PMID- 19154478
TI  - Retroperitoneal decortication of simple renal cysts vs decortication with wadding
      using perirenal fat tissue: results of a prospective randomized trial.
AB  - OBJECTIVES To evaluate, in a pilot prospective randomized trial, the safety,
      effectiveness and radiological recurrence of retroperitoneal renal cyst
      decortication compared with retroperitoneal decortication with wadding using
      perirenal pedicled fat tissue. PATIENTS AND METHODS From March 2004 to December
      2007, 40 patients with simple renal cysts were enrolled and randomized; 22 (group
      A) had a simple retroperitoneal decortication (SRD) and 18 (group B) a
      decortication with wadding of the cyst using perirenal fat tissue (RDCW). The
      following variables were recorded: age, gender, side, size on
      ultrasonography/computed tomography (CT), location, operative duration, blood
      loss, complications, pathology, presence or absence of flank pain, hypertension,
      urinary tract compression or urinary infection. The primary endpoint of this
      trial was to evaluate and compare the efficacy of both treatments. Secondary
      endpoints were safety and pain, hypertension and the resolution of urinary tract
      obstruction. RESULTS In all, 40 cysts were treated; there were no bilateral
      cysts. The mean (sd) size on CT was 11.9 (1.84) cm in group A and 12.8 (1.25) cm
      in group B (P = 0.1). All the procedures were completed laparoscopically and no
      conversion was necessary. There were no intraoperative complications. The mean
      (range) hospital stay was 3.4 (3-6) days. There was no statistically significant
      difference between the groups for all variables assessed. There was a
      radiological recurrence in three patients (14%) in group A, but none in group B
      (all successful). CONCLUSION To be completely successful, with maximum safety and
      to prevent recurrences in the treatment of renal cysts, RCDW is recommended when
      a retroperitoneal approach is chosen, especially if the cyst is located
      anteriorly. When symptom relief is considered, RCDW duplicates the results
      obtained with SRD.

PMID- 19154479
TI  - Genetic alterations and chemosensitivity profile in newly established human renal
      collecting duct carcinoma cell lines.
AB  - OBJECTIVE: To determine the genetic alterations and chemosensitivity profile of
      collecting duct carcinoma (CDC) of the kidney, as it is a rare, highly aggressive
      malignant tumour with frequent distant metastases. MATERIALS AND METHODS: We
      first established and characterized two human CDC cell lines designated AP3 and
      AP8, respectively. The CDC cell lines were assessed using microarray-based
      comparative genomic hybridization and chemosensitivity testing. RESULTS: The CDC
      cells grew in vitro as an adherent monolayer with epithelial morphology, but had
      different growth rates. The cell lines had the characteristic immunophenotype of
      CDC (high molecular weight cytokeratin-+ve/cytokeratin 7-+ve/vimentin-+ve). Both
      cell lines shared copy number gains in chromosomes 20 and X. The loci showing a
      copy number gain were SOX22 at 20p tel, topoisomerse I (TOP1) at 20q12-q13.1,
      TPD52L2 at 20q tel, 20QTEL14 at 20q tel, KAL at Xp22.3, STS 5' at Xp22.3, OCRL1
      at Xq25, AR3'at Xq11-q12, and XIST at Xq13.2, respectively. Immunoblot analysis
      confirmed that the AP3 and AP8 cell lines showed moderate and high levels of TOP1
      expression, respectively. By chemosensitivity testing, the AP8 cells were most
      sensitive to topoisomerase I and II inhibitors such as topotecan, epirubicin and
      doxorubicin, but the AP3 cells did not. The chemosensitivity to these drugs was
      paralleled by cell death via apoptosis. CONCLUSION: The results suggest that TOP1
      might be one of the molecular targets in AP8 CDC cells. Thus, these novel CDC
      cell lines will be useful for discovering therapeutic targets and developing
      effective anticancer drugs against CDC.

PMID- 19154480
TI  - Tadalafil and vardenafil vs sildenafil: a review of patient-preference studies.
AB  - The immediate objective of phosphodiesterase type 5 (PDE5) inhibitor treatment is
      to restore the ability of a man to achieve and/or maintain an erection adequate
      for sexual intercourse. As erectile dysfunction (ED) generally develops in the
      second half of life, the ultimate objective generally is not procreation, but
      quality of sexual life. Indeed, ED is known to impair quality of life
      considerably; two-thirds of men report that ED has impaired their self-esteem and
      nearly a third claim that it has damaged the relationship with their partner. It
      follows that the therapeutic success of PDE5 inhibition has an important
      subjective component, which is compounded by the subjective nature and complexity
      of sexual life in humans. This makes it very difficult for physicians to be
      certain that they have selected the optimal therapy for a couple, even after a
      thorough evaluation. The 2007 European Association of Urology Guidelines stress
      the importance of educating the patient and claim that 'the patient will choose
      the final drug after his own experience'. However, PDE5 inhibitors are typically
      used twice a week, so a patient would have to spend approximately 3 months trying
      the various compounds and dosages to achieve adequate exposure to all three PDE5
      inhibitors; this would seem an unrealistic strategy in normal clinical practice.
      The acknowledgement that the patient has an important role in therapeutic
      decisions for ED has fuelled interest in the concept of patient preference. It
      has been established that patient preference depends on three factors, i.e.
      personal characteristics, e.g. age, duration of ED, frequency and dynamics of
      sexual relations, and the characteristics of their partners, e.g. age, menopausal
      status and level of interest in sexual activity and medication profile.
      Medication features of interest include efficacy in terms of quality of erection,
      consistency of effects, rapid onset of action, long duration of action, side
      effect profile and route of administration; drug costs must also be considered if
      the medicinal product is not reimbursed.

PMID- 19154481
TI  - Prevalence of infection with high-risk human papillomavirus in women in Colombia.
AB  - The prevalence of human papillomavirus (HPV) infections in 2109 females
      inhabiting five cities of Colombia was determined. Of the 49.2% with an HPV
      infection, 59.8% were infected with more than one viral type. Species 7 (of the
      the genus Alphapapillomavirus) was associated with multiple infections. Analysis
      of the socio-demographic data revealed a statistically significant protective
      effect associated with the status of civil union (civil recognition of
      cohabitation without marriage), and indigenous ethnicity proved to be a risk
      factor for HPV infection. This is the first study comparing HPV infection among
      women from geographical regions of Colombia with different socio-cultural
      structures.

PMID- 19154482
TI  - Correlation between galactomannan antigen levels in serum and neutrophil counts
      in haematological patients with invasive aspergillosis.
AB  - The detection of circulating galactomannan (GM) in serum samples is an important
      step in the diagnosis of invasive aspergillosis (IA). The assay has been mainly
      explored in neutropenic patients, and is now used to monitor patients at high
      risk for IA. However, the performance of the assay varies greatly among studies.
      The objective of this study was to explore the impact of the neutrophil count on
      the GM serum index at the time of IA diagnosis. Ninety-nine episodes of proven or
      probable, microbiologically documented IA in 91 patients with haematological
      malignancies were studied retrospectively. Three groups were identified: groups 1
      3, with <100 polymorphonuclear neutrophils (PMN)/mm(3) (n = 18), between 100 and
      500 PMN/mm(3) (n = 21), or >500 PMN/mm(3) (n = 60), respectively. The mean GM
      index was significantly higher in group 1 than in the other groups (p <0.05).
      This finding did not change after stratifying the analysis with regard to the use
      of antibiotics likely to give false-positive GM results or with regard to
      treatment effective against fungi before the diagnosis of IA. This finding could
      be considered in the routine use of the GM antigenaemia test in non-neutropenic
      patients; a negative result or a low GM index should not eliminate the diagnosis
      of IA. This limitation calls for other microbiological tests, including analysis
      of bronchoalveolar lavage fluid, to establish a definitive diagnosis of IA.

PMID- 19154483
TI  - Upsurge of tick-borne encephalitis in the Baltic States at the time of political
      transition, independent of changes in public health practices.
AB  - Despite evidence that socio-economic factors associated with political transition
      played a major causal role in the abrupt upsurge in tick-borne encephalitis (TBE)
      in the newly independent Baltic States, doubts are still repeatedly expressed
      about the importance of these factors relative to changes in public health
      practices that may have affected merely the registration of cases. In response to
      these doubts, evidence of relevant practices of surveillance, registration,
      diagnosis, awareness and immunization is presented as taken from archived data
      and interviews with experienced medical practitioners. There were changes that
      could have had neutral, negative or positive impacts on recorded TBE incidence,
      but the variable timing in these changes at both national and regional levels is
      not consistent with their having been responsible for the epidemiological
      patterns observed in the early 1990 s.

PMID- 19154484
TI  - Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa
      isolates from cystic fibrosis patients.
AB  - In total, 40 Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients
      were included in this study. Twenty of these were collected in 1994 and 1997,
      from six CF patients, and the rest were collected from different CF patients in
      2000 and 2001. The relative expression of mRNA for the efflux pump protein MexY
      was determined by real-time PCR and correlated with susceptibilities to amikacin
      and tobramycin. The chromosomal genes mexZ, rplY, galU, PA5471 and nuoG, which
      were found to have a role in the gradual increase in MICs of aminoglycoside
      antibiotics in laboratory mutants of P. aeruginosa, were analysed. MexY mRNA
      overproduction was found in 17/20 isolates collected in 1994 and 1997, and was
      correlated with decreased susceptibility to aminoglycosides. Alteration of the
      MexXY-OprM efflux system has been the main mechanism of resistance to
      aminoglycoside antibiotics in CF P. aeruginosa isolates over the 3-year period.
      In several isolates, expression of the PA5471 gene product might have some effect
      on elevated MICs of aminoglycosides. Inactivation of rplY, galU and/or nuoG may
      explain the gradual increase in MICs of aminoglycosides in laboratory mutants but
      probably not in the CF environment, as rplY and galU were unaltered in all
      isolates, and nuoG was not expressed in only one isolate. No 16S rRNA A-site
      mutations were found in any of the four copies of the gene in 13 investigated
      isolates.

PMID- 19154485
TI  - Severe diarrhoea caused by highly ciprofloxacin-susceptible Campylobacter
      isolates.
AB  - The impact of fluoroquinolone resistance of Campylobacter jejuni and
      Campylobacter coli isolates on the outcome of the disease in sporadic
      Campylobacter infections of Finnish individuals was studied. Questionnaires were
      sent, during a 6-month study period, to patients who were stool culture-positive
      for Campylobacter spp. In total, 192 returned questionnaires were analysed and
      assessed, together with the susceptibility data of the respective bacterial
      isolates. Only one (2%) of the domestic, but half of the imported, Campylobacter
      isolates were resistant to ciprofloxacin. Ciprofloxacin resistance was not
      associated with particularly severe infection. Instead, ciprofloxacin-susceptible
      Campylobacter isolates, as compared to ciprofloxacin-resistant isolates, showed a
      tendency to cause more severe infections, characterized by bloody stools and
      hospitalization.

PMID- 19154486
TI  - Interlaboratory reproducibility of a microsatellite-based typing assay for
      Aspergillus fumigatus through the use of allelic ladders: proof of concept.
AB  - An interlaboratory study was performed with the aim of investigating the
      reproducibility of a multiplex microbial microsatellite-based typing assay for
      Aspergillus fumigatus in different settings using a variety of experimental and
      analytical conditions and with teams having variable prior microsatellite typing
      experience. In order to circumvent problems with exchange of sizing data, allelic
      ladders are introduced as a straightforward and universally applicable concept
      for standardization of such typing assays. Allelic ladders consist of mixtures of
      well-characterized reference fragments to act as reference points for the
      position in an electrophoretic trace of fragments with established repeat
      numbers. Five laboratories independently analysed six microsatellite markers in
      18 samples that were provided either as DNA or as A. fumigatus conidia. Allelic
      data were reported as repeat numbers and as sizes in nucleotides. Without the use
      of allelic ladders, size differences of up to 6.7 nucleotides were observed,
      resulting in interpretation errors of up to two repeat units. Difficulties in
      interpretation were related to non-specific amplification products (which were
      resolved with explanation) and bleed-through of the different fluorescent labels.
      In contrast, after resolution of technical or interpretive problems,
      standardization of sizing data by using allelic ladders enabled all participants
      to produce identical typing data. The use of allelic ladders as a routine part of
      molecular typing using microsatellite markers provides robust results suitable
      for interlaboratory comparisons and for deposition in a global typing database.

PMID- 19154487
TI  - Enzyme-linked immunospot assay for interferon-gamma in the diagnosis of
      tuberculous pleurisy.
AB  - Patients presenting with pleural effusion of undetermined aetiology were
      prospectively enrolled, and an enzyme-linked immunospot (ELISPOT) assay on
      pleural fluid and peripheral blood was performed. Forty patients were studied,
      including 19 with culture- or biopsy-confirmed (n = 15) or clinically compatible
      (n = 4) tuberculous pleurisy, and 21 with pleural effusions due to non
      tuberculous causes. The sensitivity, specificity and positive and negative
      predictive values of the assay were 94.7%, 85.7%, 85.7% and 94.7%, respectively,
      on pleural fluid, and 77.8%, 90.5%, 87.5% and 82.6%, respectively, on blood.
      Antigen-specific, interferon-gamma-secreting T-cells were concentrated eight to
      ten times in pleural fluid as compared with blood. Among the seven patients not
      suitable for pleural biopsy and three patients whose biopsy results were non
      diagnostic, nine had positive ELISPOT result with pleural fluid. The ELISPOT
      assay for interferon-gamma can accurately diagnose tuberculous pleurisy and is
      helpful for patients not suitable for pleural biopsy and those whose biopsy
      results are non-diagnostic.

PMID- 19154488
TI  - Candidaemia: incidence, risk factors, characteristics and outcomes in
      immunocompetent critically ill patients.
AB  - A matched case-control study was conducted to determine the risk factors for
      development of candidaemia in patients requiring intensive-care unit (ICU)
      treatment for more than 48 h. Patients were matched according to length of ICU
      stay, age, department of admission, year of admission and sex. Forty-five
      patients with candidaemia were identified (0.6 cases/1000 patient-days).
      Candidaemia developed mainly in critically ill patients with multiple organ
      failure and end-stage disease. Candida colonization and gastrointestinal surgery
      were independently associated with candidaemia. ICU and total in-hospital
      mortality were 40% and 66.7%, respectively. Candidaemia-related mortality was
      20%. Candidaemia treatment failure was the only variable associated with in
      hospital mortality (p 0.008).

PMID- 19154489
TI  - Nasal carriage of Staphylococcus aureus, including community-associated
      methicillin-resistant strains, in Queensland adults.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
      infections are emerging in southeast Queensland, Australia, but the incidence of
      carriage of CA-MRSA strains is unknown. The aim of this study was to assess the
      nasal carriage rate of S. aureus, including CA-MRSA strains, in the general adult
      population of southeast Queensland. 396 patients presenting to general practices
      in two Brisbane suburbs and 303 volunteers randomly selected from the electoral
      rolls in the same suburbs completed a medical questionnaire and had nasal swabs
      performed for S. aureus. All isolates of S. aureus underwent antibiotic
      susceptibility testing and single-nucleotide polymorphism (SNP) and binary
      typing, including determination of Panton-Valentine leukocidin (PVL). The nasal
      carriage rate of methicillin-susceptible S. aureus (MSSA) was 202/699 (28%), a
      rate similar to that found in other community-based nasal carriage studies.
      According to multivariate analysis, nasal carriage of S. aureus was associated
      with male sex, young adult age group and Caucasian ethnicity. Only two study
      isolates (one MSSA and one CA-MRSA) carried PVL. The nasal carriage rate of MRSA
      was low, at 5/699 (0.7%), and only two study participants (0.3%) had CA-MRSA
      strains. CA-MRSA is an emerging cause of infection in southeast Queensland, but
      as yet the incidence of carriage of CA-MRSA in the general community is low.

PMID- 19154490
TI  - Prevalence of penicillin and erythromycin resistance among invasive 
      Streptococcus pneumoniae isolates reported by laboratories in the  southern and
      eastern Mediterranean region.
AB  - Information about the epidemiology of resistance in Streptococcus pneumoniae
      within southern and eastern countries of the Mediterranean region is incomplete,
      as reports have been sporadic and difficult to compare. Over a 36-month period,
      from 2003 to 2005, the ARMed project collected 1298 susceptibility test results
      of invasive isolates of S. pneumoniae from blood and spinal fluid cultures
      routinely processed within 59 participating laboratories situated in Algeria,
      Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey. Overall, 26%
      (335) of isolates were reported as non-susceptible to penicillin, with the
      highest proportions being reported from Algeria (44%) and Lebanon (40%). During
      the same time period, the highest proportions of pneumococci that were not
      susceptible to erythromycin were reported from Malta (46%) and Tunisia (39%).
      Proportions of dual non-susceptibility in excess of 5% were found in laboratories
      in Algeria, Tunisia, Lebanon, Jordan and Turkey. ARMed data on the antimicrobial
      resistance epidemiology of S. pneumoniae in the southern and eastern
      Mediterranean region provided evidence of high rates of resistance, especially to
      penicillin. This evidence calls for a greater focus on the identification of
      relevant drivers of resistance and on the implemention of effective practices in
      order to address the problem of resistence.

PMID- 19154491
TI  - Serum antibodies against Panton-Valentine leukocidin in a normal population and
      during Staphylococcus aureus infection.
AB  - To determine whether Staphylococcus aureus Panton-Valentine leukocidin (PVL) is
      expressed during human infection, anti-PVL antibody titres were compared in
      patients with PVL-positive and PVL-negative staphylococcal infections, and in
      patients with no evidence of S. aureus infection. Patients with PVL-positive
      strains had higher levels of anti-PVL antibodies than individuals of both control
      groups. The median anti-PVL titre increased 8.6-fold during the course of PVL
      positive infection and 1.4-fold during PVL-negative infection. These results
      indicate that only PVL-positive S. aureus strains elicit significant anti-PVL
      antibody production in humans, and demonstrate the production of PVL during PVL
      positive S. aureus infection. The protective role of this immune response remains
      to be established.

PMID- 19154492
TI  - Management of nosocomial pneumonia on a medical ward: a comparative study of
      outcomes and costs of invasive procedures.
AB  - The goal of this study was to compare outcomes and costs of two management
      strategies for non-ventilator-associated nosocomial pneumonia (NP) in a medical
      ward. In this single-centre study, NP patients (n = 68) were randomized to
      receive non-invasive management (NIM) with immediate empirical antibiotic
      treatment (n = 34), or invasive management (IM) based on protected brush sampling
      of specimens (n = 34). The economic analysis adopted the hospital's perspective
      and took into account only direct costs. Baseline characteristics did not differ
      significantly between the two patient groups. The most frequently isolated
      organisms were Staphylococcus (25.4%), Streptococcus (23.7%) and Pseudomonas
      (18.6%) species. The 28-day clinical cure rate did not differ notably between the
      two groups (NIM, 79.4%; IM, 73.5%). Mortality at 28 days tended to be lower in
      the NIM group (10.0% vs. 21.8%). Mean antibiotic costs were lower in the IM group
      (euro194 +/- 355 vs. euro300 +/- 335, p <0.001) but overall management costs were
      similar (respectively, euro367 +/- 355 and euro346 +/- 363 in the IM and NIM
      groups, p = 0.08). With respect to both outcome and cost, this study does not
      support routine management of NP in medical wards using invasive procedures.

PMID- 19154493
TI  - Severe penile injuries: a problem of severity and reconstruction.
AB  - OBJECTIVES: To report our experience of treating severe penile injuries with
      different causes and treatments, as penile trauma presents a difficult physical
      and psychological problem, and the type and extent of injury varies from mild to
      severe, sometimes even with total amputation. PATIENTS AND METHODS: We analysed
      retrospectively 43 patients (mean age 28 years, range 5-52 years) with severe
      penile injuries referred to us from March 1999 to August 2007. The causes of
      penile injuries differed, including iatrogenic trauma (20), traffic accidents
      (11), burns (three), self-amputation (two), ritual circumcision (two), penile
      fracture (two), gunshot trauma (two) and electrocution (one). The management
      required a wide variety of surgical techniques tailored to each patient depending
      on the type and extent of injury. RESULTS: The mean (range) follow-up was 47 (10
      108) months. The aesthetic and functional results, including satisfactory sexual
      intercourse were good in 35 patients. There were complications in seven patients;
      infection after implanting an inflatable penile prosthesis in one, protrusion of
      a semirigid prosthesis in one, urethral complications (one stenosis and two
      fistulae) in three and partial skin flap necrosis in two. CONCLUSIONS: Severe
      penile injuries should be treated on an individual basis, applying different
      techniques. However, treatment can be effective and safe only in specialized
      centres.

PMID- 19154494
TI  - Differences in side-effect duration and related bother levels between
      phosphodiesterase type 5 inhibitors.
AB  - OBJECTIVE: To assess whether the longer half-life of tadalafil is associated with
      longer lasting or more severe side-effects than the other phosphodiesterase type
      5 inhibitors (PDE-5Is), as clinical trials have shown that the efficacy and
      safety of the three available are similar, but tadalafil has a half-life four
      times longer than the other two drugs. PATIENTS AND METHODS: Treatment-naive men
      beginning PDE5-I therapy were recruited from a specialist clinic. Data on the
      type and duration of drug-associated side-effects were collected prospectively.
      Levels of bother were assessed with a visual analogue scale (VAS). Differences in
      type, duration and bother of side-effect were compared between drugs. RESULTS: In
      all, 409 men provided data; there were no differences between drugs in the
      proportion of men responding, or the overall prevalence of side-effects. The mean
      duration of side-effects with tadalafil was 14.9 h, compared to 3.9 and 7.7 h for
      sildenafil and vardenafil. Of men taking tadalafil, 30% had side-effects lasting
      >12 h. There were no differences in mean VAS scores between the drugs. Individual
      side-effects caused similar levels of bother, except for facial flushing, which
      was less bothersome. CONCLUSIONS: Men taking tadalafil are at risk of prolonged
      side-effects, although levels of bother associated with these side-effects are
      not significantly greater than those seen with short-acting PDE5-Is.

PMID- 19154495
TI  - Abdominal mesh sacrocolpopexy for recurrent triple-compartment pelvic organ
      prolapse.
AB  - OBJECTIVE: To report the short- and intermediate- term outcome of safety and
      efficacy after abdominal-mesh sacrocolpopexy (MSC) for recurrent anterior,
      posterior and vault ('triple-compartment') pelvic organ prolapse (POP). PATIENTS
      AND METHODS: In a database review we identified non-neurogenic women who had MSC
      for recurrent triple-compartment POP and with a >or=6-month cystographic follow
      up. The preoperative evaluation included a history, physical examination,
      Urogenital Distress Inventory (UDI-6) and visual analogue quality-of-life (QoL)
      questionnaires, urodynamic studies, and a standing lateral voiding cysto
      urethrogram (VCUG) with rest-strain views. All surgery as performed by the same
      surgeon, using polypropylene (Marlex) mesh. Perioperative data, the VCUG at 6
      months, and interval pelvic examinations were recorded. RESULTS: Between 2000 and
      2006, 29 postmenopausal women (Caucasian, mean age 64 years, sd 11) underwent
      MSC. The mean (sd, range) operative duration was 228 (75, 170-340) min, the
      estimated blood loss 150 (100) mL and the inpatient stay 3 (1) days. At a mean
      (sd) follow-up of 23 (16) months, the physical examination showed no evidence of
      POP of grade >or=2, with mean POP-Quantification scores of -2.8 (0.4), -2.9 (0.4)
      and -9.3 (0.8) for points A(a), A(p) and C, respectively. Two patients (8%) had
      evidence of grade >or=2 cystocele at the 6-month VCUG. After MSC, four of the six
      UDI and the QoL scores were significantly lower at the last follow-up than at
      baseline, with no change in sexual or defecatory function. CONCLUSIONS: The
      objective and subjective improvement at the short and intermediate follow-up
      after MSC suggest that this is a safe and effective treatment for recurrent
      triple-compartment POP.

PMID- 19154496
TI  - Circulating mitochondrial DNA in the serum of patients with testicular germ cell
      cancer as a novel noninvasive diagnostic biomarker.
AB  - OBJECTIVE: To analyse the diagnostic and prognostic value of cell-free
      mitochondrial (mt)DNA in patients with testicular cancer, as increased levels of
      cell-free circulating mtDNA have been reported in patients with cancer. PATIENTS,
      SUBJECTS AND METHODS: In all, 74 patients with testicular cancer (seminoma in 39,
      nonseminoma in 35) and 35 healthy individuals were included in the study.
      Circulating DNA was isolated from 1 mL of serum. A quantitative real-time
      polymerase chain reaction was used to analyse the levels of a 79-bp (mtDNA-79)
      and 220 bp (mtDNA-220) fragment of the mitochondrial specific 16S-RNA. The mtDNA
      integrity was expressed as the ratio of mtDNA-220 to mtDNA-79. RESULTS: mtDNA-79
      and mtDNA-220 levels were significantly (P < 0.001) greater in patients with
      testicular cancer than in healthy individuals. The mtDNA integrity was similar in
      patients and healthy controls (P = 0.435). Receiver operator characteristic curve
      analysis showed that cell-free mtDNA (mtDNA-79) levels distinguished, with a
      sensitivity of 59.5% and a specificity of 94.3%, between patients and healthy
      individuals (area under curve, 0.787). Also, mtDNA-79 levels could be used to
      distinguish between patients (31) with conventional markers (alpha-fetoprotein,
      human chorionic gonadotrophin, placental alkaline phosphatase and lactate
      dehydrogenase) within normal ranges and healthy individuals, with a sensitivity
      of 64.5% and specificity of 91.4% (area under curve 0.797). Cell-free mtDNA
      levels were not correlated with any clinicopathological variable (pT stage, lymph
      node invasion, vascular invasion, clinical stage, International Germ Cell Cancer
      Collaborative Group classification, tumour markers; all P > 0.05). CONCLUSION:
      Cell-free mtDNA levels are greater in patients with testicular cancer and might
      provide valuable information for managing patients with testicular anomalies,
      especially those with normal levels of established tumour markers.

PMID- 19154497
TI  - Hybrid tumour 'oncocytoma-chromophobe renal cell carcinoma' of the kidney: a
      report of seven sporadic cases.
AB  - OBJECTIVES: To determine whether renal hybrid tumours (HT) appear as a specific
      clinical and radiological entity, as HT are characterized by the association of
      both oncocytes and chromophobe cells within the same tumour, and have been
      described in patients with oncocytosis and Birt-Hogg-Dube syndrome. PATIENTS AND
      METHODS: We reviewed the medical charts of 67 patients who had a partial or
      radical nephrectomy in our institution for renal oncocytoma (RO, 24), chromophobe
      renal cell carcinoma (CRCC, 36) and HT (seven), from January 2006 to October
      2007. We report the clinical, radiological and pathological characteristics of
      the seven cases of HT. RESULTS: The mean (range) age of the patients was 56 (41
      68) year. None of the seven patients had any suspicion of RO, based on computed
      tomography (CT). Two patients had a history of kidney cancer. Five patients had
      partial and two a radical nephrectomy. The mean (range) maximum tumour diameter
      was 5.5 (1.8-9) cm. Two tumours were pT1a, two were pT1b and three were pT2.
      Pathological analysis showed RO-like and CRCC-like cells intermixed (six
      patients) or distinct (one). After a median (range) follow-up of 20 (8-25)
      months, none of the patients had any evidence of disease recurrence. CONCLUSIONS:
      In a large series of patients with sporadic RO and CRCC, 10% of the tumours had
      hybrid morphological features, as described in oncocytosis and Birt-Hogg-Dube
      syndrome. We were unable to identify any specific clinical characteristic. Most
      importantly, none of these HT showed any of the radiological characteristics of
      RO.

PMID- 19154498
TI  - Localization of renal oxidative stress and inflammatory response after
      lithotripsy.
AB  - OBJECTIVE To determine if the acute renal oxidative stress and inflammation after
      extracorporeal shock wave lithotripsy (ESWL), thought to be mediated by
      ischaemia, is most severe in the portion of the kidney within the focal zone of
      the lithotripter, and if these effects result primarily from ischaemic injury.
      MATERIALS AND METHODS Pigs (7-8-weeks old) received either 2000 shock waves at 24
      kV to the lower-pole calyx of one kidney or unilateral renal ischaemia for 1 h. A
      third group (sham) received no treatment. Timed urine and blood samples were
      taken for analysis of lipid peroxidation and the inflammatory cytokines, tumour
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). At 4 h after
      treatment, kidneys were removed and samples of cortex and medulla were frozen for
      analysis of cytokines and heme oxygenase-1 (HO-1). RESULTS ESWL did not affect
      urinary excretion of malondialdehyde, but did elicit an eight-fold induction of
      HO-1 in the portion of the renal medulla within the focal zone of the
      lithotripter (F2), while remaining unchanged elsewhere in the treated kidney.
      There was no induction of HO-1 in renal tissue after ischaemia-reperfusion.
      Urinary excretion of TNF-alpha increased from the lithotripsy-treated kidney by 1
      h after treatment, but was unaffected by ischaemia-reperfusion. As with the HO-1
      response after lithotripsy, IL-6 increased only in the renal medulla at F2. By
      contrast, ischaemia-reperfusion increased IL-6 in all samples from the treated
      kidney. CONCLUSION These findings show that the acute oxidative stress and
      inflammatory responses to ESWL are localized to the renal medulla at F2.
      Furthermore, the differing patterns of markers of injury for ESWL and ischaemia
      reperfusion suggest that ischaemia is not the principal cause of the injury
      response after ESWL.

PMID- 19154499
TI  - A population-based comparison of survival after nephrectomy vs nonsurgical
      management for small renal masses.
AB  - OBJECTIVE: To examine population-based rates of cancer-specific and other-cause
      mortality after either non-surgical management (NSM) or nephrectomy, in patients
      with small renal masses, as several reports from selected institutions support
      the applicability of surveillance in patients with small renal masses, but there
      are no population-based studies confirming the general applicability of this
      therapy. PATIENTS AND METHODS: Of 43 143 patients with renal cell carcinoma
      identified in the 1988-2004 Surveillance, Epidemiology and End Results database,
      10 291 had localized small renal masses (<or=4 cm) and were offered NSM (433,
      4.2%) or nephrectomy (9858, 95.8%). Univariable matched and multivariable
      unmatched competing-risks regression models were used in the analyses. RESULTS:
      Cumulative incidence plots based on unmatched data, where the effect of other
      cause mortality was controlled for, showed a 5.2%, 6.5% and 9.4% survival benefit
      for nephrectomy vs NSM at 1, 2 and 5 years after nephrectomy or diagnosis,
      respectively. The same magnitude of the benefit (4.5%, 5.6% and 8.0%) persisted
      in analyses matched for age, tumour size and year of diagnosis or of nephrectomy.
      Finally, in multivariable analyses, treatment type, age, tumour size and year of
      diagnosis or of nephrectomy were independent predictors. CONCLUSION: Relative to
      nephrectomy, NSM appears to undermine the overall and cancer-specific survival of
      patients with small renal masses by as much as 9.4%, at 5 years.

PMID- 19154500
TI  - A tertiary experience of vesico-vaginal and urethro-vaginal fistula repair:
      factors predicting success.
AB  - OBJECTIVE: To review the outcomes of all patients referred with vesico-vaginal (V
      VF) and urethro-vaginal (UVF) fistulae to a tertiary centre, and to investigate
      the patient, fistula and surgical factors relevant to success. PATIENTS AND
      METHODS: We reviewed retrospectively the case-notes of 41 consecutive patients
      (32 with V VF; nine with UVF) treated between January 2000 and January 2006.
      RESULTS: All patients were tertiary referrals, eight after failed local repairs.
      Four patients were unsalvageable and had a supravesical diversion. In all there
      were 47 repairs (23 transvaginal; 24 transabdominal) on 37 patients by two
      specialist surgeons. The fistula was closed in 92%; five V VF and one UVF
      required a second procedure, and one V VF a third procedure. One patient with a V
      VF awaits a second attempt at repair. In one V VF (one attempt) and one UVF
      (three attempts) the procedure failed and the patient had a diversion. A
      transvaginal approach cured all 11 patients with a V VF and eight of nine with a
      UVF, whilst an abdominal approach used for larger/complex fistulae was successful
      in 18 of 24 (75%) attempts (P = 0.13). The major determinants of success were
      fistula size (>3 cm; P = 0.02) and the availability of tissue for interposition.
      V VF repairs using Martius/omental interposition were mostly successful, whilst
      abdominal repairs in which omentum was unavailable tended to fail (37.5% cure; P
      = 0.002). CONCLUSIONS: Despite varied aetiology, V VF/UVF were repaired
      successfully in 92% of patients. Complex (V VF) fistulae were challenging and a
      quarter of these required more than one attempt. Failure of repair was more
      likely in larger fistulae (>3 cm) requiring an abdominal approach, if omental
      interposition was not possible. Good-quality tissue interposition for complex
      fistula is essential for a successful outcome.

PMID- 19154501
TI  - Surgical debridement of mineral pitch and nonviable penile tissue using water-jet
      power: a preliminary report.
AB  - OBJECTIVE: To report our experience of debriding genital wounds embedded with
      mineral pitch (MP) from asphalt, using a water jet-powered surgical tool, the
      Versajet Hydrosurgery System (VHS, Smith and Nephew, Key Largo, FL) before
      reconstruction. PATIENTS AND METHODS: We used the VHS for penile debridement in
      two patients. The first was 42-year-old Hispanic man involved in a truck-bike
      accident, who was dragged approximately 60 m after the collision. He presented
      with 25% body-surface abrasion impregnated with MP. The scrotal soft tissue had
      been lost and both testicles were exposed and ruptured, with no viable tissue.
      Moreover, the distal two-thirds of the penile urethra and the ventral glans were
      completely damaged and his penis entirely degloved. Several procedures were
      required for surgical debridement and reconstruction, including the skin grafting
      to 25% of his body surface. All surgical debridement was done with the VHS. A
      modified Thiersch-Duplay urethroplasty was used over a 16 F Foley catheter to
      reconstruct the missing urethra. The second patient was a 32-year-old man with no
      previous medical history, who presented with Fournier's gangrene after a penile
      abrasion following unprotected sexual intercourse. He required several surgical
      debridements. The VHS was applied to an 8 x 10 cm area, followed by a free-radial
      graft to the inferior epigastric. RESULTS: The clinical follow-up was 9 and 6
      months, respectively; both patients had satisfactory granulation tissue and
      proper wound healing. Neither of the patients had infection after surgical
      debridement with the VHS, even when used in the case of Fournier's gangrene.
      CONCLUSION: The VHS appears to be effective for genital soft-tissue surgical
      debridement even when the tissue is impregnated with MP or infected, without
      causing any spread of infection. Larger series and a longer follow-up are needed
      to validate the effectiveness of the VHS in managing complex genital wounds.

PMID- 19154502
TI  - Adhesion molecules alpha, beta and gamma-catenin as prognostic factors of tumour
      progression in upper urinary tract urothelial tumours: the role of AKT-P/GSK
      3beta/beta-catenin pathway.
AB  - OBJECTIVES To evaluate alpha, beta and gamma-catenin expression in upper urinary
      tract urothelial tumours (UUTC) and determine their value as prognostic factors;
      to investigate the correlation between the catenin complex and the AKT pathway.
      PATIENTS AND METHODS We retrospectively analysed 114 consecutive patients treated
      at our institution from 1990 to 2004; the mean follow-up was 54 months. Tumour
      samples were available from 70 patients, and included in tissue microarrays for
      immunohistochemical analysis. The antibodies used were anti-alpha, -beta and
      gamma-catenin, and antiphospho-AKT. The prognostic value of the expression of
      these molecules was analysed using tumour progression and cancer-specific
      survival as end-points. RESULTS Of the 114 patients, 27% developed tumour
      progression; the cancer-specific and overall survival were 77% and 60.6%,
      respectively. Abnormal alpha, beta and gamma-catenin expression was found in 44
      (63%), 22 (31%) and 28 (41%) patients, respectively; the abnormal catenin
      expression patterns correlated with each other. Positive cytoplasm phospho-AKT
      expression was found in 27 (39%) patients. Three of them were found to have
      cytoplasmic beta-catenin accumulation and none of them nuclear expression. beta
      catenin expression was the only one that was an independent marker of tumour
      progression, with a hazard ratio (95% confidence interval) of 3.1(1.2-8.6),
      together with grade (7.1, 1.2-55.8) and stage (4.6, 2.1-10). In the cancer
      specific survival analysis, again beta-catenin was an independent prognostic
      factor (3.4, 1-11.5) together with stage (4.6, 2.2-9.8). CONCLUSIONS The loss of
      the normal membrane beta-catenin expression constitutes an independent factor of
      tumour progression and cancer-specific survival. Our data suggest that the
      AKT/GSK3beta/beta-catenin signalling pathway is not activated in the UUTC
      carcinogenesis.

PMID- 19154503
TI  - A chemosensitivity test to individualize intravesical treatment for non-muscle
      invasive bladder cancer.
AB  - OBJECTIVE: To describe the design of a new chemosensitivity assay based on the
      expression of genes involved in the resistance to standard intravesical regimens,
      to allow individualization of therapy for high-risk non-muscle-invasive bladder
      cancer. PATIENTS AND METHODS: To date, 35 patients with high-risk non-muscle
      invasive bladder cancer have been enrolled, all candidates for transurethral
      resection of the bladder (TURB) followed by intravesical treatment. The
      intravesical regimen was chosen according to the risk profile of each patient.
      All patients were evaluated by cystoscopy 3 and 6 months after TURB. According to
      the molecular characterization of each tumour, our team of molecular oncologists
      determined for each patient a molecular profile of chemosensitivity to BCG,
      mitomycin c, anthracyclines and gemcitabine. This profile was then correlated to
      the response to intravesical therapy 6 months after TURB. RESULTS: This
      chemosensitivity test was able to predict response to treatment in 96% of
      patients. The assay is easy to perform, inexpensive and quick. CONCLUSION: Our
      results, although preliminary, are encouraging for the future of an
      individualized therapeutic approach, with the aim to provide a higher treatment
      success rate while sparing patients unnecessary toxicity from drugs that are not
      suited for their tumours.

PMID- 19154504
TI  - Laparoscopic complete urinary tract exenteration with the specimen withdrawn
      transvaginally.
AB  - OBJECTIVE To describe the technique of laparoscopic complete urinary tract
      exenteration (LaCUTE), where specimens are withdrawn en bloc through the vagina,
      and to compare our results for patients had this procedure with those who had
      surgery by traditional open methods PATIENTS AND METHODS From February 2006 to
      June 2008, five patients had LaCUTE and three CUTE at our institute. The surgical
      procedure included bilateral nephroureterectomy, bilateral pelvic
      lymphadenectomy, radical cystourethrectomy, radical hysterectomy, bilateral
      salpingo-oophorectomy. RESULTS In the LaCUTE group the mean (range) patient age
      was 58 (46-73) years, the blood loss was 378 (290-490) mL, the operative duration
      was 492 (405-560) min and the hospital stay was 12.2 (9-17) days. All patients
      had negative surgical margins on pathological examination. The LaCUTE group had
      significantly less blood loss but longer surgery than the open group. At a mean
      follow-up of 14.5 and 16.0 months, respectively, there was no evidence of
      recurrent cancer in both groups. CONCLUSIONS With further experience and
      improvement in surgical techniques, LaCUTE with vaginal specimen en bloc
      withdrawal will become feasible for uraemic female patients with urothelial
      cancer.

PMID- 19154505
TI  - Reliability and validity of the King's Health Questionnaire for lower urinary
      tract symptoms in both genders.
AB  - OBJECTIVE: To investigate the reliability and validity of the King's Health
      Questionnaire (KHQ) in both genders, which was originally developed as a health
      related quality of life (HRQoL) questionnaire for female urinary incontinence for
      general lower urinary tract symptoms (LUTS). SUBJECTS AND METHODS: Data from the
      International Prostate Symptom Score (IPSS) and KHQ obtained from 179 men and 75
      women consulting urologists (Sample A) were analysed. Cronbach's alpha
      coefficient and inter-domain correlation were calculated for reliability and
      validity assessment, respectively. Factor analysis was used to explore the
      underlying factor structure of the KHQ. KHQ scores of sample A were compared with
      those of 330 men and 418 women consulting general practitioners (Sample B).
      RESULTS: Internal consistency of KHQ was acceptable with a Crohnbach's alpha of
      0.721-0.915 in the total population of sample A. Correlation analysis showed
      convergent validity among 'Physical Limitations', 'Role Limitation' and 'Social
      Limitations' and discriminant validity among 'Personal Relationship', 'Emotion's
      and 'Sleep/Energy'. Factor analysis showed three underlying components to explain
      convergent and discriminant validity. In both sample A and sample B, HRQoL was
      impaired in the eight domains according to IPSS severity. KHQ scores of domains
      other than 'General Health Perception' in sample B were lower than those in
      sample A. CONCLUSION: The KHQ can be used as a HRQoL questionnaire for LUTS in
      both genders. In the future, it is expected that the KHQ could be used in
      clinical studies for benign prostate hyperplasia and other conditions.

PMID- 19154506
TI  - Short-term assessment of a tension-free vaginal tape for treating female stress
      urinary incontinence.
AB  - OBJECTIVE: To evaluate the short-term surgical complications and results of a
      tension-free vaginal tape (TVT) system (TVT-Secur, Gynecare, Ethicon, Somerville,
      NJ, USA) in the treatment of female stress urinary incontinence (SUI). PATIENTS
      AND METHODS: TVT-Secur was applied to 107 women with SUI through a vaginal
      incision and left abutting the urethra. Postoperative pain, complications, de
      novo lower urinary tract symptoms, incontinence cure rate and the King's Health
      Questionnaire (KHQ) score were evaluated. RESULTS: The operative duration was 12
      min; the mean pain score was 2.3 and only one patient had transient voiding
      difficulties. After a mean follow-up of 15 months, 71% of the patients were dry
      and 14% improved. The KHQ scores decreased significantly for most subscores.
      Urgency appeared de novo in six patients (5.6%), and vaginal erosion required one
      TVT-Secur explantation. CONCLUSION: This study shows that TVT-Secur is a simple
      and safe treatment for female SUI, but before recommending this sling as a first
      choice for treating SUI, TVT-Secur must pass the test of time and comparative
      studies with conventional slings.

PMID- 19154507
TI  - Final analysis of a phase II trial using sorafenib for metastatic castration
      resistant prostate cancer.
AB  - OBJECTIVE: To determine if sorafenib is associated with an improved 4-month
      probability of progression-free survival, using radiographic and clinical
      criteria alone, in patients with metastatic castration-resistant prostate cancer.
      Secondary endpoints included pharmacokinetics, toxicity analysis and overall
      survival. PATIENTS AND METHODS: The study was an open-label, phase II, two-stage
      design, focusing on the results from the second stage, as criteria for
      progression were modified after completing the first stage. Sorafenib was given
      at a dose of 400 mg orally twice daily in 28-day cycles. Clinical and laboratory
      assessments were done every 4 weeks, and radiographic scans were obtained every 8
      weeks. RESULTS: Twenty-four patients were accrued in the second stage; the median
      (range) age was 66 (49-85) years, the on-study prostate-specific antigen level
      was 68.45 (5.8-995) ng/mL, the Gleason score 8 (6-9) and Eastern Cooperative
      Oncology Group status 1 (in 17 patients). Of the 24 patients, 21 had previous
      chemotherapy with docetaxel. All patients had bony metastases, either alone (in
      11) or with soft-tissue disease (in 13). One patient had a partial response; 10
      patients had stable disease (median duration 18 weeks, range 15-48). At a median
      potential follow-up of 27.2 months, the median progression-free survival was 3.7
      months and the median overall survival was 18.0 months. For the whole trial of 46
      patients the median survival was 18.3 months. Most frequent toxicities included
      hand-foot skin reaction (grade 2 in nine patients, grade 3 in three), rash,
      abnormalities in liver function tests, and fatigue. CONCLUSIONS: Sorafenib has
      moderate activity as a second-line treatment for metastatic castration-resistant
      prostate cancer.

PMID- 19154509
TI  - Gleason score 7 screen-detected prostate cancers initially managed expectantly:
      outcomes in 50 men.
AB  - OBJECTIVE To assess whether men newly diagnosed with Gleason 7 prostate cancer
      are eligible for active surveillance (AS) instead of radical treatment. AS is an
      appropriate initial strategy in selected men who are presently diagnosed with
      prostate cancer, as many tumours will not progress during a patient's lifetime.
      PATIENTS AND METHODS Cancer-specific-, overall and treatment-free survival were
      analysed retrospectively in men with Gleason score 7 cancer who were initially
      managed expectantly. All were screen-detected in four centres of the European
      Randomized Study of Screening for Prostate Cancer. RESULTS In 50 men active
      therapy was initially withheld if they had Gleason 7 disease; 29 of 50 (58%)
      would otherwise have been suitable for AS, as they had a prostate-specific
      antigen (PSA) level of < or =10.0 ng/mL, a PSA density of <0.2 ng/mL/mL, stage
      T1c/T2, and two or fewer positive biopsy-cores; 44 of 50 (88%) had a Gleason
      score 3 + 4 = 7. The mean (range) age of the men was 69.5 (59.6-76.2) years and
      the median (interquartile range) follow-up was 2.6 (0.8-5.0) years; the mean
      American Society of Anesthesiologists score was 1.8. The 6-year cancer-specific
      survival (nine patients at risk) was 100%, which sharply contrasted with the 68%
      overall survival. Men alive at the time of analysis had a favourable PSA level
      and PSA-doubling time. The 6-year treatment-free survival was only 59%, with most
      patients switching to active therapy, justified on the basis of their PSA level.
      However, men with otherwise favourable tumour characteristics and a Gleason score
      of 3 + 4 = 7 remained treatment-free significantly longer than their counterparts
      with unfavourable other tumour features and a Gleason score of 4 + 3 = 7.
      CONCLUSION In selected patients with screen-detected Gleason 3 + 4 = 7 prostate
      cancer, AS might be an option, especially in those with comorbidity and/or a
      short life-expectancy.

PMID- 19154508
TI  - Lower urinary tract symptoms increase the risk of falls in older men.
AB  - OBJECTIVE To evaluate the association of lower urinary tract symptoms (LUTS) with
      the risk of falls in elderly community-dwelling men. SUBJECTS AND METHODS We
      evaluated 5872 participants in the Osteoporotic Fractures in Men, a prospective
      cohort study of risk factors for falls and osteoporotic fractures among community
      dwelling men aged > or =65 years. The primary outcome was the 1-year cumulative
      incidence of falls in men with moderate or severe, vs mild LUTS at baseline, as
      measured by the American Urological Association Symptom Index. We used Poisson
      regression models and considered multiple variables as potential confounders.
      RESULTS At baseline, 3188 (54%) reported mild, 2301 (39%) moderate, and 383 (7%)
      severe LUTS. Compared with men who had mild symptoms, the adjusted 1-year
      cumulative incidence of falls was significantly higher among men with moderate or
      severe LUTS. The risk of at least one fall was increased by 11% among those with
      moderate (relative risk 1.11, 95% confidence interval, CI, 1.01-1.22; P = 0.02)
      and by 33% among those with severe LUTS (1.33, 1.15-1.53; P < 0.001). Further,
      those with moderate LUTS had a 21% (1.21, 1.05-1.40; P = 0.01) and those with
      severe LUTS a 63% (1.63, 1.31-2.02; P < 0.001) greater risk of at least two
      falls. LUTS most strongly associated with falls were urinary urgency, difficulty
      initiating urination, and nocturia. CONCLUSIONS Moderate and severe LUTS
      independently increase the 1-year risk of falls, particularly recurrent falls, in
      community-dwelling older men. Because of the serious consequences of falls, these
      results might justify the routine assessment of LUTS with a validated
      questionnaire in the primary care of this population.

PMID- 19154510
TI  - Prostate cancer diagnosis in the new millennium: strengths and weaknesses of
      prostate-specific antigen and the discovery and clinical evaluation of prostate
      cancer gene 3 (PCA3).
AB  - The decision to take a prostate biopsy is traditionally guided by a digital
      rectal examination and measurement of serum total prostate-specific antigen
      (tPSA). However, both techniques are subject to inherent weaknesses. The prostate
      cancer gene 3 (PCA3), a gene-based marker, specific for prostate cancer,
      supplements the predictive power of tPSA to improve diagnosis of disease.
      Including this new marker in the standard of care for men at risk of prostate
      cancer should be considered, as it presents marked potential for better decision
      making for a prostate biopsy and for improving overall patient care.

PMID- 19154511
TI  - Early onset of fibrosis within the arterial media in a rat model of type 2
      diabetes mellitus with erectile dysfunction.
AB  - OBJECTIVES: To determine, in the obese Zucker fa/fa rat (OZR), whether the loss
      in smooth muscle cells (SMCs) as well as the increase in fibrosis that occurs
      within the corpora cavernosa accompanying corporal veno-occlusive dysfunction
      (CVOD), also occurs within the media of the arterial tree. MATERIALS AND METHODS:
      The penis and aorta from both 7-month-old male diabetic OZR (5 months of
      diabetes) and aged-matched nondiabetic lean Zucker rats (LZR) rats were harvested
      (eight per group). The penis and aorta were subjected to histo- or
      immnohistochemistry, followed by quantitative image analysis (QIA) to determine
      the contents of SMC, collagen and the pro-fibrotic transforming growth factor
      (TGF)beta1. The turnover of SMCs was assessed by terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick-end labelling (TUNEL) and proliferating
      cell nuclear antigen (PCNA) assays. Quantitative Western blots determined
      calponin (SMC marker) and PCNA, and hydroxyproline was used for collagen. In
      vitro relaxation of corporal strips was measured. RESULTS: In vitro relaxation of
      corporal tissue from OZR was considerably less than in the LZR. In the media of
      the penile dorsal artery (PDA) of OZR, there was a considerable reduction in the
      SMC content and the SMC/collagen ratio, as well as an increase in apoptosis, but
      there were no changes in PCNA or TGFbeta1 expression, or in the intima
      media/lumen ratio. In the aorta of the OZR, in contrast to the PDA, there was a
      reduction in PCNA as well as a more pronounced decrease in the SMC/collagen
      ratio, mainly from an increase in collagen, but there were no changes in TGFbeta1
      or the wall/lumen morphometry. In the OZR, Western blots of aortic tissue
      confirmed the decrease in PCNA and a reduction in the SMC marker calponin.
      CONCLUSIONS: These data show that 5 months after the onset of hyperglycaemia in
      the OZR, the rats develop both abnormal corporal SMC relaxation and a generalized
      fibrosis of the arterial media of both the large and small diameter vessels. It
      is possible that this pan-fibrosis of the media of the arterial system might
      contribute to the diabetes-related ED that occurs during this period in this rat
      model.

PMID- 19154512
TI  - Draping and associated equipment for indwelling catheter manipulation by hospital
      staff: an assessment of attitudes and adequacy.
AB  - OBJECTIVE: To address the usability and safety aspects of current equipment for
      indwelling urinary catheter (IDC) manipulation, by assessing the attitudes of
      doctors and nurses to infection control, occupational health and environmental
      waste, and the perceived adequacy of available catheter packs, particularly
      drapes, when performing such manipulations. SUBJECTS AND METHODS: A self
      administered survey instrument was created using an online database and completed
      by doctors and nurses. The survey covered basic demographics and experience with
      IDC, attitudes to infection control, occupational health and safety, and the
      environment, as well as adequacy of current equipment in containing spillage of
      urine and/or blood. RESULTS: In all, 87 doctors and 228 nurses completed 315 of
      350 (90%) surveys. Doctors and nurses were concerned about infection control,
      occupational health and safety issues, and environmental waste. Incidents
      involving spillage of urine and/or blood often go unreported. There were no
      differences between nurses and doctors having specialist training in urology or
      experience (P > 0.05). The second major finding is that available catheter packs,
      particularly drapes, when manipulating IDCs, are inadequate and spillage is
      likely. These findings were more pronounced in doctors and those with urology
      training (P < 0.05). CONCLUSION: The attitudes of health professionals involved
      with IDC manipulations are consistent with other fields, as is the under
      reporting of episodes of contamination by bodily fluids. The current equipment,
      particularly drapes, are inadequate for containing urine and blood, leading to
      infection control, occupational health, environmental and cost implications.

PMID- 19154513
TI  - Preface. The year in human and medical genetics.

PMID- 19154514
TI  - The year in human and medical genetics. Highlights of 2007-2008.
AB  - The breadth and scope of new information makes difficult a selection of topics to
      be included in a limited review of highlights of the year. Admittedly, the
      choices are idiosyncratic. The eight topics presented here are (1) structural and
      copy number variants in the human genome; (2) progress in defining genetic
      factors in the etiology of schizophrenia; (3) microRNAs in central nervous system
      development and function; (4) progress in elucidation of risk factors for complex
      common disorders through large scale association studies; (5) epigenetics and the
      epigenomic era; (6) reprogramming of somatic cell nuclei to generate pluripotent
      stem cells; (7) new concepts regarding factors involved in sexual
      differentiation; and (8) Duffy blood group antigens: new concepts, and new
      discoveries on the role of these antigens in malaria and HIV-AIDS.

PMID- 19154515
TI  - On the molecular etiology of Cornelia de Lange syndrome.
AB  - Cornelia de Lange syndrome (CdLS) is genetically heterogeneous and is usually
      sporadic, occurring approximately once per 10,000 births. CdLS individuals
      display diverse and variable deficits in growth, mental development, limbs, and
      organs. In the past few years it has been shown that CdLS is caused by gene
      mutations affecting proteins involved in sister chromatid cohesion. Studies in
      model organisms, and more recently in human cells, have revealed, somewhat
      unexpectedly, that the developmental deficits in CdLS likely arise from changes
      in gene expression. The mechanisms by which cohesion factors regulate gene
      expression remain to be elucidated, but current data suggest that they likely
      regulate transcription in multiple ways.

PMID- 19154516
TI  - Progress in the understanding of the genetic etiology of vertebral segmentation
      disorders in humans.
AB  - Vertebral malformations contribute substantially to the pathophysiology of
      kyphosis and scoliosis, common health problems associated with back and neck
      pain, disability, cosmetic disfigurement, and functional distress. This review
      explores (1) recent advances in the understanding of the molecular embryology
      underlying vertebral development and relevance to elucidation of etiologies of
      several known human vertebral malformation syndromes; (2) outcomes of molecular
      studies elucidating genetic contributions to congenital and sporadic vertebral
      malformation; and (3) complex interrelationships between genetic and
      environmental factors that contribute to the pathogenesis of isolated syndromic
      and nonsyndromic congenital vertebral malformation. Discussion includes
      exploration of the importance of establishing improved classification systems for
      vertebral malformation, future directions in molecular and genetic research
      approaches to vertebral malformation, and translational value of research efforts
      to clinical management and genetic counseling of affected individuals and their
      families.

PMID- 19154517
TI  - Chimerism in black southern African patients with true hermaphroditism
      46,XX/47XY,+21 and 46,XX/46,XY.
AB  - True hermaphroditism is defined by the presence of both testicular and ovarian
      tissue in an individual. True hermaphrodites usually present at birth with
      ambiguous genitalia, and subsequent invasive investigations are needed to confirm
      the diagnosis. Several large cohorts of black South Africans with true
      hermaphroditism have been described, and by far the majority of those
      investigated had a 46,XX karyotype, with absence of the SRY sequence. This paper
      represents the first report of the molecular investigation of mosiacism/chimerism
      as the cause of hermaphroditism in black southern African patients. It is the
      second report worldwide of a 46,XX/47,XY,+21 chimera, with the first described in
      a Japanese infant in 1994. Case 1 in the present study is a child who is a
      46,XX/47,XY,+21 tetragametic chimera. Molecular studies revealed two paternal and
      two maternal alleles at four of ten STR loci investigated and three alleles at
      four of these loci. The young boy exhibited no features of Down syndrome, other
      than a unilateral single palmar crease. Cases 2 and 3 both have a 46,XX/46,XY
      karyotype. Chimerism is supported by molecular analysis in Case 2, and molecular
      studies were not done for Case 3.

PMID- 19154518
TI  - Combined tarsal and carpal tunnel syndrome in mucolipidosis type III. A case
      study and review.
AB  - Mucolipidosis type III (MLIII) (MIM# 252600) is an uncommon autosomal recessive
      disorder that results from uridine 5'-diphosphate-N-acetylglucosamine: lysosomal
      hydrolase N-acetyl-1-phosphotransferase or UDP-GlcNAc 1-phosphotransferase
      deficiency. Clinical manifestations include developmental delay, short stature
      and other structural abnormalities. Less common clinical features, such as carpal
      tunnel syndrome, claw hand deformities, trigger fingers, and claw toes have
      previously been reported, but no specific association with tarsal tunnel syndrome
      has been reported in the literature. Tarsal tunnel syndrome is caused by
      entrapment of the posterior tibialis nerve in the tunnel formed by the medial
      malleolus of the ankle and the flexor retinaculum. It causes pain in the heel and
      sole of the foot as well as abnormal sensation in the distribution area of nervus
      tibialis posterior. In adults, the most common cause described is a ganglion. The
      phenomenon is rare in children and the published series are small. This case
      report portrays the presentation of a young girl with breath-holding spells
      secondary to painful bilateral tarsal tunnel syndrome and trigger fingers
      subsequently diagnosed with MLIII.

PMID- 19154519
TI  - Clinical characteristics of an Afrikaner founder population recruited for a
      schizophrenia genetic study.
AB  - The clinical characteristics of an Afrikaner founder population sample recruited
      for a schizophrenia genetic study are described. Comparisons on several clinical
      characteristics between this sample and a U.S. sample of schizophrenia patients
      show that generalization of findings in a founder population to the population at
      large is applicable. The assessment of the frequency of the 22q11 deletion in
      Afrikaner schizophrenia patients is approximately 2%, similar to findings in a
      U.S. sample. Results of analysis of early non-psychotic deviant behavior in
      subjects under the age of 10 years in the Afrikaner population broadly replicated
      findings in a U.S. sample. Approximately half of male schizophrenia patients and
      a quarter of female patients in the Afrikaner schizophrenia database used or
      abused cannabis. Male users of cannabis with severe early deviant behavior had
      the lowest mean age of criteria onset, namely 18.4 years. These findings confirm
      previous findings, indicating that early deviance is linked to later outcome of
      disease. The clinical characteristics and premorbid variables in 12 childhood
      onset Afrikaner schizophrenia patients thus far recruited in this study compare
      favorably with what is known about childhood-onset schizophrenia in a U.S.
      sample. The prevalence of co-morbid OCD/OCS in this Afrikaner schizophrenia
      founder sample was 13.2% which is in keeping with that of co-morbid OCD in
      schizophrenia, estimated at 12.2% by the U.S. National Institute of Mental
      Health. These findings confirm that the clinical characteristics of a
      schizophrenia sample drawn from the Afrikaner founder population can be
      generalized to the schizophrenia population at large when compared to findings
      reported in the literature.

PMID- 19154520
TI  - Nuclear and mitochondrial genome defects in autisms.
AB  - In this review we will evaluate evidence that altered gene dosage and structure
      impacts neurodevelopment and neural connectivity through deleterious effects on
      synaptic structure and function, and evidence that the latter are key
      contributors to the risk for autism. We will review information on alterations of
      structure of mitochondrial DNA and abnormal mitochondrial function in autism and
      indications that interactions of the nuclear and mitochondrial genomes may play a
      role in autism pathogenesis. In a final section we will present data derived
      using Affymetrix SNP 6.0 microarray analysis of DNA of a number of subjects and
      parents recruited to our autism spectrum disorders project. We include data on
      two sets of monozygotic twins. Collectively these data provide additional
      evidence of nuclear and mitochondrial genome imbalance in autism and evidence of
      specific candidate genes in autism. We present data on dosage changes in genes
      that map on the X chromosomes and the Y chromosome. Precise analyses of Y located
      genes are often difficult because of the high degree of homology of X- and Y
      related genes. However, continued efforts to analyze the latter are important,
      given the consistent evidence for a 4:1 ratio of males to females affected by
      autism. It is also important to consider whether environmental factors play a
      role in generating the nuclear and mitochondrial genomic instability we have
      observed. The study of autism will benefit from a move to analysis of pathways
      and multigene clusters for identification of subtypes that share a specific
      genetic etiology.

PMID- 19154521
TI  - Genetic calcium signaling abnormalities in the central nervous system: seizures,
      migraine, and autism.
AB  - The calcium ion is one of the most versatile, ancient, and universal of
      biological signaling molecules, known to regulate physiological systems at every
      level from membrane potential and ion transporters to kinases and transcription
      factors. Disruptions of intracellular calcium homeostasis underlie a host of
      emerging diseases, the calciumopathies. Cytosolic calcium signals originate
      either as extracellular calcium enters through plasma membrane ion channels or
      from the release of an intracellular store in the endoplasmic reticulum (ER) via
      inositol triphosphate receptor and ryanodine receptor channels. Therefore, to a
      large extent, calciumopathies represent a subset of the channelopathies, but
      include regulatory pathways and the mitochondria, the major intracellular calcium
      repository that dynamically participates with the ER stores in calcium signaling,
      thereby integrating cellular energy metabolism into these pathways, a process of
      emerging importance in the analysis of the neurodegenerative and neuropsychiatric
      diseases. Many of the calciumopathies are common complex polygenic diseases, but
      leads to their understanding come most prominently from rare monogenic
      channelopathy paradigms. Monogenic forms of common neuronal disease phenotypes
      such as seizures, ataxia, and migraine-produce a constitutionally hyperexcitable
      tissue that is susceptible to periodic decompensations. The gene families and
      genetic lesions underlying familial hemiplegic migraine, FHM1/CACNA1A,
      FHM2/ATP1A2, and FHM3/SCN1A, and monogenic mitochondrial migraine syndromes,
      provide a robust platform from which genes, such as CACNA1C, which encodes the
      calcium channel mutated in Timothy syndrome, can be evaluated for their role in
      autism and bipolar disease.

PMID- 19154522
TI  - Clinical utility of array CGH for the detection of chromosomal imbalances
      associated with mental retardation and multiple congenital anomalies.
AB  - Microarray-based comparative genomic hybridization (array CGH) has revolutionized
      clinical cytogenetics, as it provides a relatively quick method to scan the
      genome for gains and losses of chromosomal material with significantly higher
      resolution and greater clinical yield than was previously possible. A number of
      different array CGH platforms have emerged and are being used successfully in the
      diagnostic setting. In the past few years, these new methodologies have led to
      the identification of novel genomic disorders in patients with developmental
      delay/mental retardation and/or multiple congenital anomalies (DD/MR/MCA) as well
      as the discovery that each individual carries inherited copy number variations
      (CNV) whose contributions to genetic variation and complex disease are not yet
      well understood. Although array CGH is currently being used as an adjunct test to
      standard karyotype analysis, it is likely to become the genetic test of choice,
      especially in cases of idiopathic MR/MCA.

PMID- 19154523
TI  - Omega-3 fatty acids, vitamin C and Zn supplementation in asthmatic children: a
      randomized self-controlled study.
AB  - OBJECTIVES: Bronchial asthma is a chronic inflammatory airways disease.
      Nutritional intervention is an important tool to decrease the severity of many
      chronic inflammatory diseases including asthma. The aim of this study is to
      evaluate the role of omega-3 fatty acids, vitamin C and Zn in children with
      moderately persistent asthma. PATIENTS AND METHODS: Randomly assigned, placebo
      self-controlled 60 children with moderate persistent asthma completed the study,
      were subjected to alternating phases of supplementation with omega-3 fatty acids,
      vitamin C and Zn either singly or in combination separated with washout phases.
      Childhood asthma control test (C-ACT), pulmonary function tests and sputum
      inflammatory markers were evaluated at the beginning of the study and at the end
      of each therapeutic phase. RESULTS: There was a significant improvement of C-ACT,
      pulmonary function tests and sputum inflammatory markers with diet
      supplementation with omega-3 fatty acids, vitamin C and Zn (p < 0.001*). There
      was also significant improvement with the combined use of the three
      supplementations than single use of any one of them (p < 0.001*). CONCLUSION:
      Diet supplementation with omega-3 fatty acids, Zn and vitamin C significantly
      improved asthma control test, pulmonary function tests and pulmonary inflammatory
      markers in children with moderately persistent bronchial asthma either singly or
      in combination.

PMID- 19154524
TI  - The Conners' 10-item scale: findings in a total population of Swedish 10-11-year
      old children.
AB  - AIM: To present normative data for the Swedish version of the Conners' 10-item
      scale, to validate the scale by comparing children with and without attention
      deficit/hyperactivity disorder (ADHD), to explore the factor structure of this
      scale and to investigate behavioural characteristics and gender differences among
      10- to 11-year-old children, as rated by parents and teachers respectively.
      METHODS: Parents and teachers rated 509 10- to 11-year-old children (261 boys and
      248 girls) from a population-based cohort in a Swedish municipality. RESULTS: The
      Conners' 10-item scale discriminated very well between children with and without
      ADHD. Confirmatory factor analyses confirmed a two-dimensional structure of the
      scale with items measuring restless/impulsive behaviour in one factor and items
      measuring emotional lability in another. An ANOVA revealed that parents and
      teachers reported different behavioural characteristics in boys as compared to
      girls. CONCLUSION: The Conners' 10-item scale is a valid screening instrument for
      identification of ADHD. The two subscales can be used separately, in addition to
      the total score, to get a more detailed picture of the child's behaviour. Parents
      and teachers pay attention to different aspects of problem behaviour in boys and
      girls. The less disruptive behaviour of girls needs to be highlighted.

PMID- 19154525
TI  - Early working memory and maternal communication in toddlers born very low birth
      weight.
AB  - AIM: Early working memory is emerging as an important indicator of developmental
      outcome predicting later cognitive, behavioural and academic competencies. The
      current study compared early working memory in a sample of toddlers (18-22
      months) born very low birth weight (VLBW; n = 40) and full term (n = 51) and the
      relationship between early working memory, mental developmental index (MDI), and
      maternal communication in both samples. METHODS: Early working memory, measured
      by object permanence; Bayley mental developmental index; and maternal
      communication, coded during mother-toddler play interaction, were examined in 39
      toddlers born VLBW and 41 toddlers born full term. RESULTS: Toddlers born VLBW
      were found to be 6.4 times less likely to demonstrate attainment of object
      permanence than were toddlers born full term, adjusting for age at testing. MDI
      and maternal communication were found to be positively associated with attainment
      of object permanence in the VLBW group only. CONCLUSION: The difference found in
      the early working memory performance of toddlers born VLBW, compared with those
      born full term, emphasizes the importance of assessing early working memory in at
      risk populations, while the maternal communication finding highlights potential
      targets of intervention for improving working memory in toddlers born VLBW.

PMID- 19154526
TI  - Pulse oximetry screening as a complementary strategy to detect critical
      congenital heart defects.
AB  - OBJECTIVE: To compare strategies with and without first-day of life pulse
      oximetry screening to detect critical congenital heart defects (CCHDs). STUDY
      DESIGN: Population based study including all live born infants in Norway in 2005
      and 2006 (n = 116 057). Postductal (foot) arterial oxygen saturation (SpO(2)) was
      measured in apparently healthy newborns after transferral to the nursery, with
      SpO(2) < 95% as cut-off point. Out of 57 959 live births in the hospitals
      performing pulse oximetry screening, 50 008 (86%) were screened. RESULTS: A total
      of 136 CCHDs (1.2 per 1000) were diagnosed, 38 (28%) of these prenatally. Of the
      CCHDs detected after birth, 44/50 (88%) were detected before discharge in the
      population offered pulse oximetry screening (25 by pulse oximetry), compared to
      37/48 (77%) in the non-screened population (p = 0.15). Median times for
      diagnosing CCHDs in-hospital before discharge were 6 and 16 h after birth
      respectively (p < 0.0001). In the screened population 6/50 (12%) CCHDs were
      missed and recognized after discharge because of symptoms. Two of the six missed
      cases failed the pulse oximetry screening, but were overlooked (echocardiography
      not performed before discharge). If these cases had been recognized, 4/50 (8%)
      would have been missed compared to 11/48 (23%) in the non-screened population (p
      = 0.05). Of the cases missed, 14/17 (82%) had left-sided obstructive lesions.
      CONCLUSION: First-day of life pulse oximetry screening provides early in-hospital
      detection of CCHDs and may reduce the number missed and diagnosed after
      discharge.

PMID- 19154527
TI  - Congenital diaphragmatic hernia: an overview of the etiology and current
      management.
AB  - AIM: To review provide an overview of the etiology and current strategies in the
      management of congenital diaphragmatic hernia (CDH). METHODS: We did a
      comprehensive review of research trends, evidence based studies and epidemiologic
      studies. RESULTS: CDH is a life-threatening pathology in infants, and a major
      cause of death due to the pulmonary hypoplasia and pulmonary hypertension. There
      is much research related to elucidating the etiology of CDH and developing
      management strategies to improve the outcomes in these infants. CONCLUSION: An
      early diagnosis with increased understanding of this disease is a crucial factor
      for a timely approach to managing the critically ill infant, and to offer the
      potential for improved outcomes and substantial reductions in morbidity.

PMID- 19154528
TI  - Epidemiology of fatal electrical injuries in children and adolescents.

PMID- 19154529
TI  - A population-based study of genotypic and phenotypic variability in children with
      spinal muscular atrophy.
AB  - AIMS: To describe the occurrence of spinal muscular atrophy (SMA) in childhood;
      to evaluate if any of the genes in the SMA region on chromosome 5q13 correlates
      with disease severity; to make genotype-phenotype correlations; to evaluate the
      variability of different disease alleles in carriers and the sensitivity of
      multiplex ligation-dependent probe amplification (MLPA) for detecting carriers.
      METHODS: In a population-based study from Western Sweden MLPA was used to
      determine the copy-numbers of several genes in the SMA region (SMN1, SMN2, BIRC1,
      GTF2H2 and SERF1A) in SMA-patients and their parents. RESULTS: We estimated the
      incidence of SMN1-related SMA in childhood at 1 in 11 800 live births and
      confirmed the relationship between the number of SMN2 copies and the severity of
      disease. No other direct relationships were found. All but one of the analysed
      parents were confirmed as carriers by MLPA analysis. A total of at least 30
      different disease alleles were identified and no specific disease allele
      represented more than 15% of the total. CONCLUSION: The childhood incidence of
      SMA in the Swedish population is around 1 in 12,000 live births and it is
      unlikely that there is any founder effect involved in SMA in western Sweden.

PMID- 19154531
TI  - Malignant melanoma of soft parts arising from Tenon's capsule.

PMID- 19154532
TI  - The significance of second lumbrical-interosseous latency comparison in the
      diagnosis of carpal tunnel syndrome.
AB  - AIM: To assess the significance of the second lumbrical-interosseous latency (2LI
      DML) comparison in the diagnosis of carpal tunnel syndrome (CTS). PATIENTS AND
      METHODS: We examined 150 consecutive hands of patients referred with suspected
      CTS, using the 2LI-DML test and other standard measures of median nerve function.
      Correlations of the 2LI-DML test with standard tests were computed. RESULTS:
      Hundred and four hands were electrophysiologically confirmed to have CTS. The 2LI
      DML test was abnormal in 99/104 (95.2%) hands with CTS with a mean value of 1.54
      +/- 1.12 ms. Among the other measures, the orthodromic median-ulnar palmar
      velocity comparison was the most frequently abnormal test (95/104 hands, 91.3%),
      followed by the double-peak morphology of orthodromic sensory action potential
      from digit 4 (94/104, 90.4%). The 2LI-DML test significantly correlated, either
      positively or negatively, with all other standard tests. CONCLUSION: The 2LI-DML
      comparison is highly sensitive in diagnosing CTS, even in mild cases in which
      standard tests fail to detect abnormalities.

PMID- 19154533
TI  - Post-stroke depression: can we predict its development from the acute stroke
      phase?
AB  - OBJECTIVES: To identify possible predictive factors for post-stroke depression
      (PSD) in the acute phase of stroke. METHODS: The study design was prospective,
      observational cohort study of patients with acute cerebral infarction (CI).
      Neurological and neuropsychological evaluations were conducted within the first
      10 days from the onset of stroke and repeated at the 3-month follow-up. DSM-IV
      criteria were used to define PSD. RESULTS: From a total of 85 patients with CI,
      59 patients completed the 3-month follow-up and 17 of them (28.8 %) fulfilled PSD
      criteria at the 3-month follow-up. Melancholy index of the Hamilton Depression
      Rankin Scale (HDRS) was associated with a risk three times greater than that of
      PSD at the 3-month follow-up in the univariate analysis (OR 3.07; 95% CI 1.53
      6.16; P = 0.002) with no significant influence of stroke severity or the location
      of brain infarction (right or left side). The receiver operating characteristic
      curves pointed to a melancholy index > or =1.5 as the optimal cut-off level
      associated with the development of PSD at the 3-month follow-up. CONCLUSIONS:
      Melancholy index of the HDRS > or =1.5 could be a useful clinical tool to detect
      patients with acute stroke at high risk of developing PSD.

PMID- 19154534
TI  - Poor tolerability of high dose ascorbic acid in a population of genetically
      confirmed adult Charcot-Marie-Tooth 1A patients.
AB  - BACKGROUND: Preclinical studies have suggested that ascorbic acid (AA) treatment
      in a mouse model of Charcot-Marie-Tooth type 1A (CMT1A) improves motor function
      and prolongs lifespan. AIMS: I sought to determine the safety and tolerability of
      AA in adult patients with CMT1A. METHODS: An open-label cohort-controlled 2-year
      pilot study was used to evaluate the tolerability of 5 g of AA daily. Secondary
      measurements consisted of clinical and electrophysiological measurements at 0,
      12, and 24 months in CMT1A patients. RESULTS: Twelve CMT1A patients received AA
      and 10 CMT1A patients formed a cohort group followed in identical manner. Five
      (42%) patients tolerated this dose of AA for the entire 2-year span, with six
      patients (50%) developing intolerable gastrointestinal side effects. No
      significant differences in clinical, disability, or electrophysiological
      measurements occurred between baseline and final follow-up in patients receiving
      AA when compared with cohorts. CONCLUSIONS: High dose AA was not well tolerated
      in all adult CMT1A patients who may be susceptible to gastrointestinal adverse
      effects of AA. Studies with greater powers to detect efficacy will be required to
      test the validity of AA as a therapy in CMT1A patients. Doses lower than 5 g of
      AA daily may be required for maintenance of tolerability in the CMT1A population.

PMID- 19154535
TI  - Multiple sclerosis incidence in the era of measles-mumps-rubella mass
      vaccinations.
AB  - BACKGROUND: Viral childhood infections may be involved in the multiple sclerosis
      (MS) pathogenesis. Following national Swedish vaccination programs, measles
      sharply declined in the 1970s, and measles, mumps, and rubella were virtually
      eliminated in cohorts born from 1981. OBJECTIVES: To examine whether the
      vaccination induced reduction in these infections influences the MS incidence. In
      addition, the public health aspect justified an early evaluation of beneficial as
      well as harmful effects of mass vaccinations. MATERIALS AND METHODS: From an
      incidence material of 534 MS patients, born 1959-1990, we selected one
      unvaccinated cohort and four cohorts, each corresponding to a vaccination program
      (MS patients = 251). RESULTS: With the ability to detect a decrease by 30-35%,
      and an increase by 37-48% in the MS incidence in the first three cohorts, we
      found no vaccination related MS incidence changes. The background MS incidence
      showed a significant gradual age dependent increase. CONCLUSIONS: While the
      present follow-up provided limited power in the last cohort, there is no evidence
      as yet that the radical decline in three viral infections influenced the MS
      incidence. However, the increasing background MS incidence of unknown cause may
      have concealed a reduction in MS risk associated with mass vaccinations.

PMID- 19154536
TI  - Relation between ictal asystole and cardiac sympathetic dysfunction shown by MIBG
      SPECT.
AB  - OBJECTIVE: Tachyarrhythmias are common during epileptic seizures while
      bradyarrhythmias or asystoles are less frequent. Ictal asystole might be related
      to epilepsy-induced cardiac sympathetic denervation. METHODS: To evaluate cardiac
      post-ganglionic denervation in epilepsy patients with ictal asystoles we assessed
      I123-meta-iodobenzylguanidine (MIBG) as a marker of post-ganglionic cardiac
      norepinephrine-uptake, using single photon emission computed tomography (MIBG
      SPECT). RESULTS: In five of 844 patients with presurgical video
      electroencephalography-monitoring, we recorded ictal asystoles during nine of 37
      seizures. Asystole patients underwent cardiologic examination (Holter
      electrocardiogram, echocardiogram) and cardiac MIBG-SPECT. We compared cardiac
      MIBG uptake in the asystole patients to the uptake in 18 temporal lobe epilepsy
      (TLE) patients without bradyarrhythmias and in 14 controls without cardiac or
      neurological disease. As the cardiological examinations were unremarkable in all
      subjects, the heart/mediastinum-MIBG-uptake ratios (H/M-ratios) differed
      significantly between the three groups (P = 0.004). H/M-ratios were lower in
      asystole TLE patients (mean +/- SD: 1.58 +/- 0.3) than in patients without
      asystole (1.81 +/- 0.18; P = 0.037) or controls (1.96 +/- 0.16). CONCLUSIONS:
      Pronounced reduction in cardiac MIBG uptake of asystole patients indicates post
      ganglionic cardiac catecholamine disturbance. Impaired sympathetic cardiac
      innervation limits adjustment and heart rate modulation, and may increase the
      risk of asystole and ultimately sudden unexpected death in epilepsy (SUDEP).

PMID- 19154537
TI  - Epistasis between tau phosphorylation regulating genes (CDK5R1 and GSK-3beta) and
      Alzheimer's disease risk.
AB  - OBJECTIVE: Glycogen synthase kinase-3beta (GSK-3beta) and cyclin-dependent kinase
      5 (CDK5) have been implicated as two major protein kinases involved in the
      abnormal hyperphosphorylation of tau in Alzheimer's disease (AD) brain, and the
      development of neurofibrillary tangles. CDK5 regulatory subunit 1 (CDK5R1)
      encodes for p35, a protein required for activation of CDK5. As both CDK5R1 and
      GSK-3beta genes are related to phosphorylation of tau, we examined the combined
      contribution of these genes to the susceptibility for AD. METHODS: In a case
      control study in 283 AD patients and 263 healthy controls, we examined the
      combined effects between CDK5R1 (3'-UTR, rs735555) and GSK-3beta (-50, rs334558)
      polymorphisms on susceptibility to AD. RESULTS: Subjects carrying both the CDK5R1
      (3'-UTR, rs735555) AA genotype and the GSK-3beta (-50, rs334558) CC genotype had
      a 12.5-fold decrease in AD risk (adjusted by age, sex and APOE status OR = 0.08,
      95% CI = 0.01-0.76, P = 0.03), suggesting synergistic effects (epistasis) between
      both genes. CONCLUSION: These data support a role for tau phosphorylation
      regulating genes in risk for AD.

PMID- 19154538
TI  - A-G-4G haplotype of PAI-1 gene polymorphisms -844 G/A, HindIII G/C, and -675
      4G/5G is associated with increased risk of ischemic stroke caused by small vessel
      disease.
AB  - BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is the major inhibitor
      of fibrinolysis. It was reported that PAI-1 gene polymorphisms affected PAI-1
      level and might therefore influence the risk of vascular diseases, including
      stroke. We studied the association of three common polymorphisms in PAI-1 gene (
      844 G/A, -675 4G/5G, and HindIII G/C) with the odds of different causes of
      ischemic stroke. METHODS: We studied 390 patients with ischemic stroke due to
      large vessel disease (n = 117), small vessel disease (n = 121), and
      cardioembolism (n = 152) as well as 291 controls. The etiology of ischemic stroke
      was established using TOAST criteria. PAI-1 polymorphisms were genotyped with
      restriction fragment length polymorphism and single strand conformation
      polymorphism method. RESULTS: A-G-4G haplotype of PAI-1 gene was found more
      frequently in stroke patients with small vessel disease than in control subjects
      (44.9% vs 35.7%; P = 0.02). No association was found between investigated
      genotype or allele frequencies and distinct causes of ischemic stroke.
      CONCLUSIONS: Our results demonstrate that A-G-4G PAI-1 gene haplotype is
      associated with increased risk of small vessel disease stroke, but this study
      does not support an association of -844 G/A, -675 4G/5G, and HindIII G/C PAI-1
      gene polymorphisms with particular etiology of ischemic stroke.

PMID- 19154539
TI  - MR peri-CSF lesions and CSF oligoclonal bands in Italian multiple sclerosis
      patients.
AB  - OBJECTIVES: We investigated the association between brain lesion distribution and
      the presence of oligoclonal IgG bands (OCBs) in Italian multiple sclerosis (MS)
      patients. MATERIALS AND METHODS: We retrospectively selected brain magnetic
      resonance imaging (MRI) uniformly performed in 56 relapsing patients (41 patients
      OCB positive). RESULTS: Brain lesions in periventricular areas occurred in 92.86%
      of the patients (100% OCB+ and 73.33% OCB-) (P = 0.004), but we did not find a
      significant difference for their median volume (P = 0.553) and median number (P =
      0.606) between the two groups. Parenchymal lesions occurred in 76.8% of the
      patients with a similar distribution (P = 1.00) and no significant difference in
      the median volume (P = 0.818) and number (P = 0.643) between the two groups.
      CONCLUSIONS: The present study on cohort of Italian MS patients demonstrated a
      lack of correlation between lesion distribution and OCBs, suggesting that B cells
      producing them could be localized both in meningeal niches and cerebral
      parenchyma.

PMID- 19154540
TI  - Memory with emotional content, brain amygdala and Alzheimer's disease.
AB  - OBJECTIVES: A highly adaptive aspect of human memory is the enhancement of
      explicit, consciously accessible memory by emotional stimuli. We studied the
      performance of Alzheimer's disease (AD) patients and elderly controls using a
      memory battery with emotional content, and we correlated these results with the
      amygdala and hippocampus volume. METHODS: Twenty controls and 20 early AD
      patients were subjected to the International Affective Picture System (IAPS) and
      to magnetic resonance imaging-based volumetric measurements of the medial
      temporal lobe structures. RESULTS: The results show that excluding control group
      subjects with 5 or more years of schooling, both groups showed improvement with
      pleasant or unpleasant figures for the IAPS in an immediate free recall test.
      Likewise, in a delayed free recall test, both the controls and the AD group
      showed improvement for pleasant pictures, when education factor was not
      controlled. The AD group showed improvement in the immediate and delayed free
      recall test proportional to the medial temporal lobe structures, with no
      significant clinical correlation between affective valence and amygdala volume.
      CONCLUSION: AD patients can correctly identify emotions, at least at this early
      stage, but this does not improve their memory performance.

PMID- 19154541
TI  - Pattern of skeletal muscle involvement in primary dysferlinopathies: a whole-body
      3.0-T magnetic resonance imaging study.
AB  - OBJECTIVES AND METHODS: Mutations in the gene encoding dysferlin cause limb
      girdle muscular dystrophy type 2B (LGMD2B), distal Miyoshi myopathy (MM), and a
      rare form of distal anterior compartment myopathy. To study the correlations
      between clinical manifestations and muscle imaging changes we conducted a 3.0-T
      magnetic resonance imaging (MRI) study in six German patients with primary
      dysferlinopathies defined by absence of dysferlin expression in muscle (MM, n =
      3; LGMD2B, n = 2; hyperCKemia without clinical symptoms, n = 1). RESULTS:
      Patients with manifest myopathy had widespread muscular pathology. In analogy to
      previous imaging studies, we confirmed an involvement of the anterior and
      posterior thigh compartments and a predominant involvement of posterior lower
      legs. However, our whole-body MRI study further provided evidence of signal
      alterations in the glutei, erector spinae and shoulder girdle muscles.
      Correlation of clinical findings with imaging demonstrated the potential of MRI
      to detect subclinical muscle pathology. CONCLUSIONS: Whole-body 3.0-T MRI is a
      non-invasive method to demonstrate various degrees of skeletal muscle alterations
      and disease progression in muscular dystrophies. Furthermore, whole-body high
      field MRI may serve as a helpful diagnostic tool in differentiating primary
      dysferlinopathies from other forms of LGMD and distal myopathies.

PMID- 19154542
TI  - Sural nerve biopsy may predict future nerve dysfunction.
AB  - OBJECTIVE: Sural nerve pathology in peripheral neuropathy shows correlation with
      clinical findings and neurophysiological tests. The aim was to investigate
      progression of nerve dysfunction over time in relation to a baseline nerve
      biopsy. METHODS: Baseline myelinated nerve fiber density (MNFD) was assessed in
      sural nerve biopsies from 10 men with type 2 diabetes, 10 with impaired and 10
      with normal glucose tolerance. Nerve conduction and quantitative perception
      thresholds were estimated at baseline and follow-up (7-10 years later). RESULTS:
      Subjects with low MNFD (< or = 4700 fibers/mm(2)) showed decline of peroneal
      amplitude (P < 0.02) and conduction velocity (P < 0.04), as well as median nerve
      sensory amplitude (P < 0.05) and motor conduction velocity (P < 0.04) from
      baseline to follow-up. In linear regression analyses, diabetes influenced decline
      of nerve conduction. MNFD correlated negatively with body mass index (r = -0.469;
      P < 0.02). CONCLUSION: Low MNFD may predict progression of neurophysiological
      dysfunction and links obesity to myelinated nerve fiber loss.

PMID- 19154543
TI  - Dual sensitization to rat and mouse urinary allergens reflects cross-reactive
      molecules rather than atopy.
AB  - BACKGROUND: Sensitization to rats and mice can develop in laboratory animal
      workers exposed to only one species. Reasons for this dual sensitization are
      unclear but may reflect a genetic predisposition to developing allergy (atopy) or
      alternatively cross-reactivity between rat and mouse urinary allergens. We
      examined cross-reactivity between rat and mouse urine and the effect atopy has on
      dual sensitization in laboratory animal workers. METHODS: In a cross-sectional
      study the frequency of sensitization to rat and/or mouse was analysed in 498
      employees exposed to both rat and mouse at work and 220 to rat only. RAST
      inhibitions, western blots and blot inhibitions were carried out on a subset of
      five individuals to assess cross-reactivity. RESULTS: Fourteen per cent of
      workers were sensitized to rats and 9% to mouse. Over half (62%) of rat
      sensitized individuals were also mouse sensitized and the majority (91%) of mouse
      sensitized individuals were also rat sensitized. IgE cross-reactivity was
      demonstrated between rat and mouse urine using RAST inhibitions. Rates of atopy
      did not differ between rat only sensitized individuals compared with those
      sensitized to both species. Sensitization to cats and rabbits was more common
      amongst those with dual sensitization. CONCLUSIONS: Dual sensitization to rat and
      mouse reflects IgE cross-reactivity rather than atopy. Individuals with dual
      sensitization are more likely to be sensitized to other animal allergens. These
      findings will have implications for individuals working with only one rodent
      species who develop sensitization and symptoms to be aware of the potential for
      allergy to other species.

PMID- 19154544
TI  - Regarding the putative identity of a moth (Thaumetopoea spp.) allergen.

PMID- 19154545
TI  - Birch pollen allergen Bet v 1 binds to and is transported through conjunctival
      epithelium in allergic patients.
AB  - BACKGROUND: Previous work in type-I pollen allergies has mainly focused on
      lymphocytes and immune responses. Here, we begin to analyse with a systems
      biology view the differences in conjunctival epithelium obtained from healthy and
      allergic subjects. METHODS: Transcriptomics analysis combined with light and
      electron microscopic analysis of birch pollen allergen Bet v 1 located within
      conjunctival epithelial cells and tissues from birch allergic subjects and
      healthy controls was carried out. RESULTS: Bet v 1 pollen allergen bound to
      conjunctival epithelial cells within minutes after the exposure even during the
      nonsymptomatic winter season only in allergic, but not in healthy individuals.
      Light- and electron microscopy showed that Bet v 1 was transported through the
      epithelium within lipid rafts/caveolae and reached mast cells only in allergic
      patients, but not in healthy individuals. Transcriptomics yielded 22 putative
      receptors expressed at higher levels in allergic epithelium compared with healthy
      specimens. A literature search indicated that out of these receptors, eight (i.e.
      37%) were associated with lipid rafts/caveolae, which suggested again that Bet v
      1 transport is lipid raft/caveola-dependent. CONCLUSIONS: We show a clear
      difference in the binding and uptake of Bet v 1 allergen by conjunctival
      epithelial cells in allergic vs healthy subjects and several putative lipid
      raft/caveolar receptors were identified, which could mediate or be co-transported
      with this entry. The application of discovery driven methodologies on human
      conjunctival epithelial cells and tissues can provide new hypotheses worth a
      further analysis to the molecular mechanisms of a complex multifactorial disease
      such as type-I birch pollen allergy.

PMID- 19154546
TI  - Serum 25-hydroxyvitamin D and IgE - a significant but nonlinear relationship.
AB  - BACKGROUND: Hormonal vitamin D system affects the determination of T-cell
      responses. It is unknown if there is an association between vitamin D status and
      allergic conditions. Our aim was to investigate differences in serum IgE
      concentrations by vitamin D status [measured by 25(OH)D] and by a genetic
      variation in a key vitamin D activation enzyme (CYP27B1) previously shown to be
      associated with type 1 diabetes. METHODS: 9377 participants in the 1958 British
      birth cohort completed a biomedical assessment at 45 years of age ; 7288 eligible
      participants had data on 25(OH)D and IgE, with 6429 having further information on
      CYP27B1 genotype ()1260C>A). RESULTS: There was a nonlinear association between
      25(OH)D and IgE (P-value for curvature = 0.0001). Compared with the reference
      group with the lowest IgE concentrations [25(OH)D 100-125 nmol/l], IgE
      concentrations were 29% higher (95% CI 9-48%) for participants with the 25(OH)D
      <25 nmol/l, and 56% higher (95% CI 17-95%) for participants with 25(OH)D >135
      nmol/l (adjusted for sex, month, smoking, alcohol consumption, time spent
      outside, geographical location, social class, PC/TV time, physical activity, body
      mass index and waist circumference). CYP27B1 genotype was associated with both
      25(OH)D (difference for A vs. C allele: 1.88%, 95% CI 0.37-3.4%, P = 0.01) and
      IgE concentrations ()6.59%, )11.6% to )1.42%, P = 0.01). CONCLUSIONS: These data
      suggest that there may be a threshold effect with both low and high 25(OH)D
      levels associated with elevated IgE concentrations. The same CYP27B1 allele that
      is protective of diabetes was associated with increased IgE concentrations.

PMID- 19154547
TI  - Persistent airflow obstruction in asthma of patients with Churg-Strauss syndrome
      and long-term follow-up.
AB  - BACKGROUND: Little is known about the long-term outcome of airflow obstruction in
      asthma of patients with Churg-Strauss syndrome (CSS). METHODS: We conducted a
      retrospective study of 24 consecutive patients (aged 41.1 +/- 13.5 years) with
      CSS in a single center. All had asthma (starting 8.1 +/- 9.5 years prior to the
      diagnosis of CSS), blood eosinophilia (6.1 +/- 4.4 x 10(9)/l) and systemic
      manifestations of CSS. Antineutrophil cytoplasmic antibodies were found in 7 of
      22 tested patients. Seven patients had smoked (a mean of 10 pack-years). All
      patients received oral corticosteroids, 11 cyclophosphamide and 23 inhaled
      corticosteroids. RESULTS: Airflow obstruction was found in 14 patients (70%) at
      diagnosis, and in 11 of 22 patients (50%) at the time of the clinical remission
      of CSS. The mean postbronchodilator FEV1/FVC and FEV1 were 69 +/- 12% and 74 +/-
      21% of predicted at diagnosis (n = 20); 71 +/- 10% and 92 +/- 19% of predicted at
      the clinical remission (n = 22); and 64 +/- 13% and 80 +/- 21% at last visit (n =
      13), respectively. During follow-up, postbronchodilator FEV1 increased by 30 +/-
      28% in six patients with FEV1/FVC < 70% despite inhaled therapy who received
      higher dose of oral corticosteroids. At last visit, 5 of 13 patients (38%) with
      more than 3 years of follow-up had persistent airflow obstruction as defined by
      postbronchodilator FEV1/FVC < 70% and FEV1 < 80% of predicted. CONCLUSION:
      Airflow obstruction due to uncontrolled asthma is present despite corticosteroids
      in many patients at diagnosis and at clinical remission of CSS, and during follow
      up. It may be still partly reversible with increased oral corticosteroid
      treatment.

PMID- 19154548
TI  - Detection and quantification of drug-specific T cells in penicillin allergy.
AB  - Drug allergic reactions presenting as maculo-papular exanthema (MPE) are mediated
      by drug-specific T cells. In this study, the frequency of circulating specific T
      cells was analyzed by interferon-gamma (IFN-gamma) enzyme-linked immunospot assay
      in 22 patients with an allergic MPE to amoxicillin (amox). Amox-specific
      circulating T cells were detected in 20/22 patients with frequencies ranging from
      1 : 8000 to 1 : 30 000 circulating leucocytes. No reactivity was observed in 46
      control patients, including 15 patients with immunoglobulin E-mediated allergy to
      amoxicillin, 11 patients with a history of drug-induced MPE but tolerant to
      amoxicillin and 20 healthy individuals. Furthermore, amox-specific T cells were
      still detectable several years after the occurrence of the allergic reaction even
      after strict drug avoidance. Finally, analysis of drug-specific T cells in one
      patient allergic to ticarcillin (a penicillin antibiotic distinct from amox)
      revealed the presence of IFN-gamma-producing T cells reactive to ticarcillin and
      several other betalactam antibiotics, suggesting that the IFN-gamma ELISPOT assay
      is able to detect T cell cross-reactivity against chemically related drugs. These
      findings confirm that drug-induced MPE is associated with the presence of
      specific T cells in blood and further suggest that the IFN-gamma ELISPOT is a
      sensitive assay which could improve the diagnosis of betalactam allergy.

PMID- 19154549
TI  - Developmental pathways in food allergy: a new theoretical framework.
AB  - BACKGROUND: To date, there is no model of psychosocial development based on
      empirical food allergy (FA) research. This limits the ability of clinicians,
      researchers and policy-makers to predict and evaluate the real impact of FA on
      the child, with implications for prevention, treatment, intervention and health
      policy. OBJECTIVES: To provide an integrated conceptual framework to explain the
      onset, development and maintenance of FA-related cognitions, emotions and
      behaviour, with particular attention to transition points. METHOD: Fifteen focus
      groups meetings were held with 62 children (6-15 years). Developmentally
      appropriate techniques were designed to stimulate discussion, maintain interest
      and minimize threat to children's self-esteem. Data were analysed using grounded
      theory. RESULTS: FA impacts directly on children's normal trajectory of
      psychological development in both an age- and disease-specific manner. Six key
      themes emerged from the analysis: 'meanings of food'; 'autonomy, control and self
      efficacy'; 'peer relationships'; 'risk and safety'; 'self/identity'; and 'coping
      strategies'. CONCLUSIONS: Coping with FA is more than simply a strategy, it is a
      cumulative history of interactive processes (age, gender and disease specific)
      that are embedded in a child's developmental organization. CLINICAL IMPLICATIONS:
      The early recognition and incorporation of an FA-specific developmental framework
      into a treatment plan is essential and sets the stage for an effective medical
      care and the eventual transition from paediatric to adult care. CAPSULE SUMMARY:
      This study represents a first attempt to provide an integrated developmental
      framework to explain the onset, development and maintenance of FA-related
      cognitions, emotions and behaviour.

PMID- 19154550
TI  - Identification of B-cell epitopes of Bet v 1 involved in cross-reactivity with
      food allergens.
AB  - BACKGROUND: The pollen-food syndrome (PFS) is an association of food allergies to
      fruits, nuts, and vegetables in patients with pollen allergy. Mal d 1, the major
      apple allergen, is one of the most commonly associated food allergens for birch
      pollen-allergic patients suffering from PFS. Although the reactions are due to
      cross-reactive IgE antibodies originally raised against pollen Bet v 1, not every
      Bet v 1-allergic patient develops clinical reactions towards apple. AIM OF THE
      STUDY: We speculate that distinct IgE epitopes are responsible for the clinical
      manifestation of PFS. To test this hypothesis we grafted five Mal d 1 stretches
      onto Bet v 1. The grafted regions were 7- or 8-amino acids long encompassing
      amino acids residues previously shown to be crucial for IgE recognition of Bet v
      1. METHODS: A Bet v 1-Mal d 1 chimeric protein designated BMC was expressed in
      Escherichia coli and purified to homogeneity. IgE reactivity of BMC was tested
      with patients' sera originating from (i) Bet v 1-allergic patients displaying no
      clinical symptoms upon ingestion of apples; and (ii) Bet v 1-allergic patients
      displaying allergic symptoms upon ingestion of apples and other Bet v 1-related
      foods. RESULTS AND CONCLUSION: Compared to birch pollen-allergic individuals,
      patients suffering from PFS showed significantly higher IgE reactivity with BMC
      (chimeric protein). The results suggest that the Mal d 1 regions grafted onto the
      Bet v 1 sequence comprise important IgE epitopes recognized by Bet v 1-allergic
      patients suffering from allergy to apples.

PMID- 19154551
TI  - The impact of childhood conditions and concurrent morbidities on child health and
      well-being.
AB  - BACKGROUND: Understanding the impact of illnesses and morbidities experienced by
      children and adolescents is essential to clinical and population health programme
      decision making and intervention research. This study sought to: (1) examine the
      population prevalence of physical and mental health conditions for children and
      quantify their impact on multiple dimensions of children's health and well-being;
      and (2) examine the cumulative effect of concurrent conditions. METHODS: We
      conducted a cross-sectional school-based epidemiological study of 5414 children
      and adolescents aged 5-18 years, and examined parental reports of child health
      and well-being using the parent-report Child Health Questionnaire (CHQ) PF50 13
      scales are scored on a 0-100 pt scale with clinically meaningful differences of
      five points and the presence of childhood conditions (illnesses and health
      problems). RESULTS: Asthma, dental, vision and allergies are the most commonly
      identified health problems for children and adolescents, followed by attention-
      and behaviour-related problems (asthma 17.9-23.2%, dental 11.9-22.7%, vision 7.2
      14.7%, chronic allergies 8.8-13.9%, attention problems 5.1-13.8% and behaviour
      problems 5.7-12.0%). As the number of concurrent health problems increase,
      overall health and well-being decreases substantively with mean differences in
      CHQ scale scores of 14 points (-7.69 to -21.51) for physical health conditions,
      and 28 points (-5.15 to -33.81) for mental health conditions. CONCLUSIONS:
      Children's health and well-being decreases linearly with increasing presence and
      frequency of health problems. Having three or more conditions concurrently
      significantly burdens children's health and well-being, particularly for family
      related CHQ domains, with a greater burden experienced for mental health
      conditions than physical health conditions.

PMID- 19154552
TI  - Associated features of Asperger Syndrome and their relationship to parenting
      stress.
AB  - BACKGROUND: Studies have shown an increased level of stress in parents of
      autistic children relative to parents of non-autistic children. Few studies have
      examined parenting stress specifically within the Asperger Syndrome (AS)
      population. Children with AS often have associated difficulties such as sensory
      sensitivities and problems with executive functioning (i.e. planning, inhibiting,
      shifting set). This study was designed to study parenting stress as well as to
      consider the relationship between parenting stress and some of the associated
      difficulties of AS. More specifically, the aims of this study were to demonstrate
      the following: that, as a group, parents of children with AS would report
      elevated levels of parenting stress, a finding which may be more significant for
      mothers than fathers; that children with AS show impairment in executive
      functioning as well as heightened sensory sensitivity according to parent report;
      that parent report of their child's demanding characteristics would be positively
      associated with their self-reported levels of parenting stress. METHODS:
      Participants in this study were the parents of 39 children between the ages of 5
      and 12 years, reflecting a 71% response rate, in the Lothian region of Scotland
      who completed The Parenting Stress Index, the Behavioural Rating Inventory of
      Executive Function and the Short Sensory Profile. RESULTS: The study revealed
      that both mothers and fathers of AS children reported elevated levels of
      parenting stress. There was a significant positive correlation between mother's
      parenting stress and the child's level of impairment, both with respect to
      executive dysfunction as well as sensory difficulties. CONCLUSION: The challenges
      of parenting a child with AS should not be underestimated. Further study is
      needed to explore the causative role that child impairments play in parenting
      stress and what types of interventions may prove most helpful to these families.

PMID- 19154553
TI  - Goal Attainment Scaling in paediatric rehabilitation: a report on the clinical
      training of an interdisciplinary team.
AB  - BACKGROUND: Goal Attainment Scaling (GAS) is a responsive method for individual
      goal setting and treatment evaluation. However, current knowledge about its
      reliability when used in paediatric rehabilitation treatment is insufficient and
      depends highly on standardization of the GAS method. A training programme was
      developed to introduce GAS to a team of 27 professionals from five disciplines.
      The purpose of the paper is to share the experiences of professionals and parents
      during this training. METHODS: The training consisted of three 2-h general
      discussion sessions and intensive individual feedback from the study leader (i.e.
      the first author). Feedback was given until the GAS scales met predetermined
      criteria of ordinality, described specific, measurable, acceptable, realistic
      abilities and activities in a single dimension, used the 'can-do' principle and
      could be scored within 10 min. Therapists and parents were asked to give their
      opinion by completing a questionnaire. RESULTS: One hundred and fifteen GAS
      scales were developed and scored by professionals. The development of a GAS scale
      remained a time-consuming procedure, despite the training: 45 (SD = 27) minutes
      per scale. The content criteria of GAS were found to be useful by all
      participants. Common issues requiring revision of the initial scales were equal
      scale intervals, specificity, measurability and selection of a single variable.
      After the training, 70% of the therapists and 60% of the parents regarded GAS as
      a suitable tool to improve the quality of rehabilitation treatment. Examples of
      GAS scales developed by the various disciplines are presented and discussed.
      CONCLUSIONS: The experiences reported in this paper support the further
      development of training procedures for GAS before it can be used as an outcome
      measure in effect studies. The findings may be helpful in introducing GAS in the
      field of childhood disability.

PMID- 19154554
TI  - Parenting stress in mothers and fathers of a child with a hemiparesis: sources of
      stress, intervening factors and long-term expressions of stress.
AB  - BACKGROUND: In a substantial minority of children with a hemiparesis, motor
      impairments are accompanied by behavioural problems. This combination confronts
      parents with several persistent, frequently intense, sources of stress. At the
      same time, it is likely to reduce the effectiveness of psychosocial resources,
      such as feelings of competence, which would normally buffer the impact of the
      stressors. Aim To investigate the association between motor and behavioural
      problems in children with a hemiparesis and symptoms of stress in their parents,
      with particular attention to psychosocial factors which may mediate between the
      child's problems and parents' symptoms of stress. METHOD: Questionnaires
      assessing the medical, functional and behaviour problems of the child, and the
      parents' experience of stress were completed by the mothers and fathers of 108
      children with a hemiparesis who were members of the Association for the Motor
      Handicapped in the Netherlands. RESULTS: Both parents reported (extremely) high
      levels of long-term stress significantly more frequently than parents in a
      normative sample. Indices of long-term stress were associated with the child's
      behavioural problems and, less strongly, with dysfunctionality in daily life.
      However, behavioural problems and dysfunctionality also reduced parents' feelings
      of competence and social support. A mediation analysis showed that feelings of
      incompetence and social isolation mediated between the child's problems and the
      parents' symptoms of stress. Fathers and mothers did not differ in level of
      reported stress, or in the associations between the child's problems and degree
      of experienced stress. CONCLUSION: Both parents of a child with a hemiparesis
      experience high levels of stress, which are strongly associated with feelings of
      incompetence and social isolation. This suggests that one focus of intervention
      should be the alleviation of parenting stress with particular attention to
      increasing perceived competence in the parenting role and reducing feelings of
      social isolation.

PMID- 19154555
TI  - Planning for the end of children's lives--the lifetime framework.
AB  - AIM: This paper describes the development of 'a best practice framework',
      following review of a sample of notes of children known to the Lifetime Service,
      where the child has a non-malignant life limiting condition, to improve child and
      family engagement in the planning process at the end of life. BACKGROUND: There
      is very little literature about how to engage with families to decide end of life
      plans for children with life limiting conditions. METHOD: An audit of clinical
      case notes was followed by the development of 'a best practice framework' through
      a Delphi process involving clinical practitioners. RESULTS: The 3 x 3 framework
      is presented to aid communication with parents and children at this difficult
      time of decision-making. CONCLUSION: This new framework has been well received by
      both parents and practitioners, and its use will be audited in the future.

PMID- 19154563
TI  - Unsuspected or unacknowledged depressive symptoms in young adult emergency
      department patients.
AB  - OBJECTIVES: The objective was to determine the frequency of unsuspected or
      unacknowledged depressive symptoms among young adult emergency department (ED)
      patients. METHODS: The Beck Depression Inventory-II (BDI-II) and a
      demographic/lifestyle questionnaire were administered to a cross-section of
      medically stable, English-speaking young adult ED patients (aged 18-23 years)
      with nonpsychiatric chief complaints. The frequency of moderate to severe
      depressive symptoms was determined. Group results were analyzed with descriptive
      statistics; multivariate analysis assessed for patient characteristics associated
      with depressive symptoms. RESULTS: A total of 2,898 patients were screened; 2,255
      were eligible for enrollment, and 1,264 enrolled (56%; 64% female, 42% African
      American; mean age = 21 [+/-1.7] years). Twenty-nine percent had BDI-II scores
      consistent with moderate to severe depressive symptoms. Patient characteristics
      associated with depressive symptoms included knowledge of someone who had
      intentionally hurt him- or herself (odds ratio [OR] = 2) or died a violent
      nonaccidental death (OR = 1.4), low personal income (OR = 1.8), chronic health
      issues (OR = 1.7), cigarette smoking (OR = 1.6), and African American race (OR =
      1.5). Those who attended school (OR = 0.5), engaged in frequent social activities
      (OR = 0.5), or drove a car (OR = 0.7) were less likely to have depressive
      symptoms. Patients lacked insight into their depressive symptoms. CONCLUSIONS:
      There is a high prevalence of depressive symptoms in young adult ED patients.
      Young adults often do not recognize, or are reluctant to acknowledge, depressive
      symptoms. Specific patient characteristics may be useful in deciding which young
      adults should undergo ED screening for depression.

PMID- 19154562
TI  - Randomized prospective study to evaluate child abuse documentation in the
      emergency department.
AB  - OBJECTIVES: The objective was to determine whether an educational intervention
      for health care providers would result in improved documentation of cases of
      possible physical child abuse in children <36 months old treated in the emergency
      department (ED) setting. METHODS: This study had a statewide group-randomized
      prospective trial design. Participating EDs were randomized to one of three
      intervention groups: no intervention, partial intervention, or full intervention.
      Medical records for children <36 months of age were abstracted before, during,
      and after the intervention periods for specific documentation elements. The main
      outcome measure was the change in documentation from baseline. Generalized
      estimating equations (GEEs) were used to test for intervention effect. RESULTS: A
      total of 1,575 charts from 14 hospitals EDs were abstracted. Hospital and
      demographic characteristics were similar across intervention groups. There were
      922 (59%) injury visits and 653 (41%) noninjury visits. For each specific
      documentation element, a GEE model gave p-values of >0.2 in independent tests,
      indicating no evidence of significant change in documentation after the
      intervention. Even among the 26 charts in which the possibility of physical abuse
      was noted, documentation remained variable. CONCLUSIONS: The educational
      interventions studied did not improve ED documentation of cases of possible
      physical child abuse. The need for improved health care provider education in
      child abuse identification and documentation remains. Future innovative
      educational studies to improve recognition of abuse are warranted.

PMID- 19154565
TI  - Delirium in older emergency department patients: recognition, risk factors, and
      psychomotor subtypes.
AB  - OBJECTIVES: Missing delirium in the emergency department (ED) has been described
      as a medical error, yet this diagnosis is frequently unrecognized by emergency
      physicians (EPs). Identifying a subset of patients at high risk for delirium may
      improve delirium screening compliance by EPs. The authors sought to determine how
      often delirium is missed in the ED and how often these missed cases are detected
      by admitting hospital physicians at the time of admission, to identify delirium
      risk factors in older ED patients, and to characterize delirium by psychomotor
      subtypes in the ED setting. METHODS: This cross-sectional study was a convenience
      sample of patients conducted at a tertiary care, academic ED. English-speaking
      patients who were 65 years and older and present in the ED for less than 12 hours
      at the time of enrollment were included. Patients were excluded if they refused
      consent, were previously enrolled, had severe dementia, were unarousable to
      verbal stimuli for all delirium assessments, or had incomplete data. Delirium
      status was determined by using the Confusion Assessment Method for the Intensive
      Care Unit (CAM-ICU) administered by trained research assistants (RAs).
      Recognition of delirium by emergency and hospital physicians was determined from
      the medical record, blinded to CAM-ICU status. Multivariable logistic regression
      was used to identify independent delirium risk factors. The Richmond Agitation
      and Sedation Scale was used to classify delirium by its psychomotor subtypes.
      RESULTS: Inclusion and exclusion criteria were met in 303 patients, and 25 (8.3%)
      presented to the ED with delirium. The vast majority (92.0%, 95% confidence
      interval [CI] = 74.0% to 99.0%) of delirious patients had the hypoactive
      psychomotor subtype. Of the 25 patients with delirium, 19 (76.0%, 95% CI = 54.9%
      to 90.6%) were not recognized to be delirious by the EP. Of the 16 admitted
      delirious patients who were undiagnosed by the EPs, 15 (93.8%, 95% CI = 69.8% to
      99.8%) remained unrecognized by the hospital physician at the time of admission.
      Dementia, a Katz Activities of Daily Living (ADL) < or = 4, and hearing
      impairment were independently associated with presenting with delirium in the ED.
      Based on the multivariable model, a delirium risk score was constructed.
      Dementia, Katz ADL < or = 4, and hearing impairment were weighed equally.
      Patients with higher risk scores were more likely to be CAM-ICU positive (area
      under the receiver operating characteristic [ROC] curve = 0.82). If older ED
      patients with one or more delirium risk factors were screened for delirium, 165
      (54.5%, 95% CI = 48.7% to 60.2%) would have required a delirium assessment at the
      expense of missing 1 patient with delirium, while screening 141 patients without
      delirium. CONCLUSIONS: Delirium was a common occurrence in the ED, and the vast
      majority of delirium in the ED was of the hypoactive subtype. EPs missed delirium
      in 76% of the cases. Delirium that was missed in the ED was nearly always missed
      by hospital physicians at the time of admission. Using a delirium risk score has
      the potential to improve delirium screening efficiency in the ED setting.

PMID- 19154566
TI  - Clinical trial: B vitamins improve health in patients with coeliac disease living
      on a gluten-free diet.
AB  - BACKGROUND: Patients with coeliac disease living on a gluten-free diet show
      vitamin deficiency and reduced subjective health status. AIM: To study the
      biochemical and clinical effects of B vitamin supplementation in adults with
      longstanding coeliac disease. METHODS: In a double blind placebo controlled
      multicentre trial, 65 coeliac patients (61% women) aged 45-64 years on a strict
      gluten-free diet for several years were randomized to a daily dose of 0.8 mg
      folic acid,0.5 mg cyanocobalamin and 3 mg pyridoxine or placebo for 6 months. The
      outcome measures were psychological general well-being (PGWB) and the plasma
      total homocysteine (tHcy) level, marker of B vitamin status. RESULTS: Fifty-seven
      patients (88%) completed the trial. The tHcy level was baseline median 11.7
      micromol/L (7.4-23.0), significantly higher than in matched population controls
      [10.2 micromol/L (6.7-22.6) (P < 0.01)]. Following vitamin supplementation, tHcy
      dropped a median of 34% (P < 0.001), accompanied by significant improvement in
      well-being (P < 0.01), notably Anxiety (P < 0.05) and Depressed Mood (P < 0.05)
      for patients with poor well-being. CONCLUSIONS: Adults with longstanding coeliac
      disease taking extra B vitamins for 6 months showed normalized tHcy and
      significant improvement in general well-being, suggesting that B vitamins should
      be considered in people advised to follow a gluten-free diet.

PMID- 19154567
TI  - Predictors of corticosteroid-dependent and corticosteroid-refractory inflammatory
      bowel disease: analysis of a Chinese cohort study.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) who are corticosteroid
      dependent or -refractory are at higher risk of developing disease- and treatment
      related complications. AIMS: To identify retrospectively clinical factors present
      at diagnosis that predict the occurrence of corticosteroid dependency and
      refractoriness in Crohn's disease (CD) and ulcerative colitis (UC) patients.
      METHODS: A total of 310 IBD patients (134 CD, 176 UC) were observed for 2140
      person years and their use of systemic corticosteroids was determined. Outcomes
      of corticosteroid dependency and refractoriness were recorded. Univariate and
      multivariate analyses were performed to determine the clinical factors associated
      with outcomes. RESULTS: Seventy-seven (57.5%) CD and 95 (54.0%) UC patients had
      received corticosteroids during study period. In CD, thrombocytosis [Hazard ratio
      (HR):3.0] predicted, whereas colonic CD (HR:0.3) negatively predicted
      corticosteroid dependency. Stricturing phenotype (HR:4.5) predicted
      corticosteroid-refractory CD. For UC, thrombocytosis (HR:3.9) and extensive
      colitis (HR:1.7) predicted corticosteroid dependency. Presence of anaemia
      (HR:10.8) at diagnosis and initial requirement of total parenteral nutrition
      (TPN) (HR:18.8) predicted corticosteroid-refractory UC. The cumulative risks of
      surgery were 17.8% and 5.4% for CD and UC patients respectively at 1 year after
      starting corticosteroids. CONCLUSIONS: Thrombocytosis at diagnosis predicted
      corticosteroid-dependency in IBD. Stricturing phenotype of CD and the presence of
      anaemia in UC predicted subsequent course of corticosteroid refractoriness.

PMID- 19154568
TI  - Clinical trial: a randomized, study comparing meperidine (pethidine) and fentanyl
      in adult gastrointestinal endoscopy.
AB  - BACKGROUND: There is little evidence to guide choice between meperidine
      (pethidine) and fentanyl for sedation for gastrointestinal endoscopy. AIM: To
      compare meperidine with fentanyl in terms of procedure time and analgesia.
      METHODS: Single centre randomized controlled trial. Patients received narcotic
      doses and midazolam at the discretion of the attending endoscopist who was
      unaware of narcotic assignment. Endoscopy and recovery times were then recorded.
      The main outcome was total procedure time, defined as endoscopy time plus
      recovery time. Patient discomfort was assessed prior to discharge via visual
      analogue scale (VAS). RESULTS: In total, 55 patients were randomized to
      meperidine [44 colonoscopy and 11 esophagogastroduodenoscopy (EGD)] and 56 to
      fentanyl (45 colonoscopy and 11 EGD). Total procedure time was shorter for those
      receiving fentanyl (mean = 87.7 min) than for those receiving meperidine (mean =
      102.9 min) (P = 0.05). The difference between the groups was explained by a
      shorter mean recovery time in the fentanyl group (63.0 min) than in the
      meperidine group (76.2 min) (P = 0.07). Based on post procedure pain scores,
      examinations with meperidine (mean = 1.99) were less painful when compared with
      those receiving fentanyl (mean = 2.86, P = 0.03). CONCLUSIONS: Fentanyl shortened
      total procedure time by reducing recovery time. A simple change in narcotic
      choice could increase endoscopy unit efficiency.

PMID- 19154569
TI  - A P2X receptor from the tardigrade species Hypsibius dujardini with fast kinetics
      and sensitivity to zinc and copper.
AB  - BACKGROUND: Orthologs of the vertebrate ATP gated P2X channels have been
      identified in Dictyostelium and green algae, demonstrating that the emergence of
      ionotropic purinergic signalling was an early event in eukaryotic evolution.
      However, the genomes of a number of animals including Drosophila melanogaster and
      Caenorhabditis elegans, both members of the Ecdysozoa superphylum, lack P2X-like
      proteins, whilst other species such as the flatworm Schistosoma mansoni have P2X
      proteins making it unclear as to what stages in evolution P2X receptors were
      lost. Here we describe the functional characterisation of a P2X receptor (HdP2X)
      from the tardigrade Hypsibius dujardini demonstrating that purinergic signalling
      is preserved in some ecdysozoa. RESULTS: ATP (EC50 approximately 44.5 microM)
      evoked transient inward currents in HdP2X with millisecond rates of activation
      and desensitisation. HdP2X is antagonised by pyridoxal-phosphate-6-azophenyl
      2',4' disulfonic acid (IC50 15.0 microM) and suramin (IC50 22.6 microM) and zinc
      and copper inhibit ATP-evoked currents with IC50 values of 62.8 microM and 19.9
      microM respectively. Site-directed mutagenesis showed that unlike vertebrate P2X
      receptors, extracellular histidines do not play a major role in coordinating
      metal binding in HdP2X. However, H306 was identified as playing a minor role in
      the actions of copper but not zinc. Ivermectin potentiated responses to ATP with
      no effect on the rates of current activation or decay. CONCLUSION: The presence
      of a P2X receptor in a tardigrade species suggests that both nematodes and
      arthropods lost their P2X genes independently, as both traditional and molecular
      phylogenies place the divergence between Nematoda and Arthropoda before their
      divergence from Tardigrada. The phylogenetic analysis performed in our study also
      clearly demonstrates that the emergence of the family of seven P2X channels in
      human and other mammalian species was a relatively recent evolutionary event that
      occurred subsequent to the split between vertebrates and invertebrates.
      Furthermore, several characteristics of HdP2X including fast kinetics with low
      ATP sensitivity, potentiation by ivermectin in a channel with fast kinetics and
      distinct copper and zinc binding sites not dependent on histidines make HdP2X a
      useful model for comparative structure-function studies allowing a better
      understanding of P2X receptors in higher organisms.

PMID- 19154571
TI  - Exogenous re-infection by a novel Streptococcus pneumoniae serotype 14 as a cause
      of recurrent meningitis in a child from The Gambia.
AB  - We report a case of an infant who experienced exogenous re-infection of
      Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis after
      apparently successful antibiotic treatment with ceftriaxone. eBURST analysis
      revealed that isolates from the two episodes of meningitis belonged to
      hypervirulent ST63 and ST3321 clonal complexes respectively.

PMID- 19154570
TI  - Technology-assisted training of arm-hand skills in stroke: concepts on
      reacquisition of motor control and therapist guidelines for rehabilitation
      technology design.
AB  - BACKGROUND: It is the purpose of this article to identify and review criteria
      that rehabilitation technology should meet in order to offer arm-hand training to
      stroke patients, based on recent principles of motor learning. METHODS: A
      literature search was conducted in PubMed, MEDLINE, CINAHL, and EMBASE (1997
      2007). RESULTS: One hundred and eighty seven scientific papers/book references
      were identified as being relevant. Rehabilitation approaches for upper limb
      training after stroke show to have shifted in the last decade from being
      analytical towards being focussed on environmentally contextual skill training
      (task-oriented training). Training programmes for enhancing motor skills use
      patient and goal-tailored exercise schedules and individual feedback on exercise
      performance. Therapist criteria for upper limb rehabilitation technology are
      suggested which are used to evaluate the strengths and weaknesses of a number of
      current technological systems. CONCLUSION: This review shows that technology for
      supporting upper limb training after stroke needs to align with the evolution in
      rehabilitation training approaches of the last decade. A major challenge for
      related technological developments is to provide engaging patient-tailored task
      oriented arm-hand training in natural environments with patient-tailored feedback
      to support (re) learning of motor skills.

PMID- 19154572
TI  - Microsatellite mapping of QTLs affecting resistance to coccidiosis (Eimeria
      tenella) in a Fayoumi x White Leghorn cross.
AB  - BACKGROUND: Avian coccidiosis is a major parasitic disease of poultry, causing
      severe economical loss to poultry production by affecting growth and feed
      efficiency of infected birds. Current control strategies using mainly drugs and
      more recently vaccination are showing drawbacks and alternative strategies are
      needed. Using genetic resistance that would limit the negative and very costly
      effects of the disease would be highly relevant. The purpose of this work was to
      detect for the first time QTL for disease resistance traits to Eimeria tenella in
      chicken by performing a genome scan in an F2 cross issued from a resistant
      Fayoumi line and a susceptible Leghorn line. RESULTS: The QTL analysis detected
      21 chromosome-wide significant QTL for the different traits related to disease
      resistance (body weight growth, plasma coloration, hematocrit, rectal temperature
      and lesion) on 6 chromosomes. Out of these, a genome-wide very significant QTL
      for body weight growth was found on GGA1, five genome-wide significant QTL for
      body weight growth, plasma coloration and hematocrit and one for plasma
      coloration were found on GGA1 and GGA6, respectively. Two genome-wide suggestive
      QTL for plasma coloration and rectal temperature were found on GGA1 and GGA2,
      respectively. Other chromosme-wide significant QTL were identified on GGA2, GGA3,
      GGA6, GGA15 and GGA23. Parent-of-origin effects were found for QTL for body
      weight growth and plasma coloration on GGA1 and GGA3. Several QTL for different
      resistance phenotypes were identified as co-localized on the same location.
      CONCLUSION: Using an F2 cross from resistant and susceptible chicken lines proved
      to be a successful strategy to identify QTL for different resistance traits to
      Eimeria tenella, opening the way for further gene identification and underlying
      mechanisms and hopefully possibilities for new breeding strategies for resistance
      to coccidiosis in the chicken. From the QTL regions identified, several candidate
      genes and relevant pathways linked to innate immune and inflammatory responses
      were suggested. These results will be combined with functional genomics
      approaches on the same lines to provide positional candidate genes for resistance
      loci for coccidiosis. Results suggested also for further analysis, models
      tackling the complexity of the genetic architecture of these correlated disease
      resistance traits including potential epistatic effects.

PMID- 19154573
TI  - Identification of novel DNA repair proteins via primary sequence, secondary
      structure, and homology.
AB  - BACKGROUND: DNA repair is the general term for the collection of critical
      mechanisms which repair many forms of DNA damage such as methylation or ionizing
      radiation. DNA repair has mainly been studied in experimental and clinical
      situations, and relatively few information-based approaches to new extracting DNA
      repair knowledge exist. As a first step, automatic detection of DNA repair
      proteins in genomes via informatics techniques is desirable; however, there are
      many forms of DNA repair and it is not a straightforward process to identify and
      classify repair proteins with a single optimal method. We perform a study of the
      ability of homology and machine learning-based methods to identify and classify
      DNA repair proteins, as well as scan vertebrate genomes for the presence of novel
      repair proteins. Combinations of primary sequence polypeptide frequency,
      secondary structure, and homology information are used as feature information for
      input to a Support Vector Machine (SVM). RESULTS: We identify that SVM techniques
      are capable of identifying portions of DNA repair protein datasets without
      admitting false positives; at low levels of false positive tolerance, homology
      can also identify and classify proteins with good performance. Secondary
      structure information provides improved performance compared to using primary
      structure alone. Furthermore, we observe that machine learning methods
      incorporating homology information perform best when data is filtered by some
      clustering technique. Analysis by applying these methodologies to the scanning of
      multiple vertebrate genomes confirms a positive correlation between the size of a
      genome and the number of DNA repair protein transcripts it is likely to contain,
      and simultaneously suggests that all organisms have a non-zero minimum number of
      repair genes. In addition, the scan result clusters several organisms' repair
      abilities in an evolutionarily consistent fashion. Analysis also identifies
      several functionally unconfirmed proteins that are highly likely to be involved
      in the repair process. A new web service, INTREPED, has been made available for
      the immediate search and annotation of DNA repair proteins in newly sequenced
      genomes. CONCLUSION: Despite complexity due to a multitude of repair pathways,
      combinations of sequence, structure, and homology with Support Vector Machines
      offer good methods in addition to existing homology searches for DNA repair
      protein identification and functional annotation. Most importantly, this study
      has uncovered relationships between the size of a genome and a genome's available
      repair repertoire, and offers a number of new predictions as well as a prediction
      service, both which reduce the search time and cost for novel repair genes and
      proteins.

PMID- 19154574
TI  - PreS1 epitope recognition in newborns after vaccination with the third-generation
      Sci-B-Vac vaccine and their relation to the antibody response to hepatitis B
      surface antigen.
AB  - BACKGROUND: Sci-B-Vac is a recombinant, hepatitis B vaccine derived from a
      mammalian cell line and containing hepatitis B surface antigen (HBsAg) as well as
      preS1 and preS2 antigens. Few studies have been performed on the antibody
      responses to preS1 in relation to the antibody to hepatitis B surface antigen
      (anti-HBs) response during immunisation of healthy children with preS-containing
      vaccines. RESULTS: In this study 28 healthy newborns were randomly selected to
      receive either 2.5 microg or 5.0 microg of the Sci-B-Vac vaccine. Children
      received three doses of vaccine according to a 0-, 1-, 6-month scheme. Antibodies
      against the S-protein and three synthetic peptides mimicking three B-cell preS1
      epitopes, (21-32 amino acid epitope), (32-47 amino acid epitope) and the C
      terminal (amino acid epitope 94-117) were determined at 6 and 9 months. Fourteen
      (50%) of the 28 newborns had detectable levels of anti-preS1 (21-32) antibodies;
      15 (54%) were anti-preS1 (32-47) reactive and 12 (43%) were anti-preS1 (94-117)
      reactive at 6 or 9 months after initiation of the vaccination. Significantly
      higher levels of anti-HBs were observed in the sera of patients with detectable
      anti-preS1 (32-47) reactivity (24 550 +/- 7375 IU/L, mean +/- SEM) as compared
      with the non-reactive sera (5991 +/- 1530 IU/L, p < 0.05). The anti-HBs levels
      were significantly lower if none (p < 0.05) or one (p < 0.025) of the preS1 (21
      32, 32-47, 94-117) peptides were recognised compared with the anti-HBs levels if
      two or three peptides were recognised. CONCLUSION: Recognition of several preS1
      epitopes, and in particular, the epitope contained within the second half of the
      hepatocyte binding site localised in the hepatitis B surface protein of the third
      generation hepatitis B vaccine is accompanied by a more pronounced antibody
      response to the S-gene-derived protein in healthy newborns.

PMID- 19154575
TI  - The effect of bacteriophages T4 and HAP1 on in vitro melanoma migration.
AB  - BACKGROUND: The antibacterial activity of bacteriophages has been described
      rather well. However, knowledge about the direct interactions of bacteriophages
      with mammalian organisms and their other, i.e. non-antibacterial, activities in
      mammalian systems is quite scarce. It must be emphasised that bacteriophages are
      natural parasites of bacteria, which in turn are parasites or symbionts of
      mammals (including humans). Bacteriophages are constantly present in mammalian
      bodies and the environment in great amounts. On the other hand, the perspective
      of the possible use of bacteriophage preparations for antibacterial therapies in
      cancer patients generates a substantial need to investigate the effects of phages
      on cancer processes. RESULTS: In these studies the migration of human and mouse
      melanoma on fibronectin was inhibited by purified T4 and HAP1 bacteriophage
      preparations. The migration of human melanoma was also inhibited by the HAP1
      phage preparation on matrigel. No response of either melanoma cell line to
      lipopolysaccharide was observed. Therefore the effect of the phage preparations
      cannot be attributed to lipopolysaccharide. No differences in the effects of T4
      and HAP1 on melanoma migration were observed. CONCLUSION: We believe that these
      observations are of importance for any further attempts to use bacteriophage
      preparations in antibacterial treatment. The risk of antibiotic-resistant
      hospital infections strongly affects cancer patients and these results suggest
      the possibility of beneficial phage treatment. We also believe that they will
      contribute to the general understanding of bacteriophage biology, as
      bacteriophages, extremely ubiquitous entities, are in permanent contact with
      human organisms.

PMID- 19154577
TI  - Genotoxic responses to titanium dioxide nanoparticles and fullerene in gpt delta
      transgenic MEF cells.
AB  - BACKGROUND: Titanium dioxide (TiO2) nanoparticles and fullerene (C60) are two
      attractive manufactured nanoparticles with great promise in industrial and
      medical applications. However, little is known about the genotoxic response of
      TiO2 nanoparticles and C60 in mammalian cells. In the present study, we
      determined the mutation fractions induced by either TiO2 nanoparticles or C60 in
      gpt delta transgenic mouse primary embryo fibroblasts (MEF) and identified
      peroxynitrite anions (ONOO-) as an essential mediator involved in such process.
      RESULTS: Both TiO2 nanoparticles and C60 dramatically increased the mutation
      yield, which could be abrogated by concurrent treatment with the endocytosis
      inhibitor, Nystatin. Under confocal scanning microscopy together with the radical
      probe dihydrorhodamine 123 (DHR 123), we found that there was a dose-dependent
      formation of ONOO- in live MEF cells exposed to either TiO2 nanoparticles or C60,
      and the protective effects of antioxidants were demonstrated by the nitric oxide
      synthase (NOS) inhibitor, NG-methyl-L-arginine (L-NMMA). Furthermore, suppression
      of cyclooxygenase-2 (COX-2) activity by using the chemical inhibitor NS-398
      significantly reduced mutation frequency of both TiO2 nanoparticles and C60.
      CONCLUSION: Our results provided novel information that both TiO2 nanoparticles
      and C60 were taken up by cells and induced kilo-base pair deletion mutations in a
      transgenic mouse mutation system. The induction of ONOO- may be a critical
      signaling event for nanoparticle genotoxicity.

PMID- 19154578
TI  - Identifying differential exon splicing using linear models and correlation
      coefficients.
AB  - BACKGROUND: With the availability of the Affymetrix exon arrays a number of tools
      have been developed to enable the analysis. These however can be expensive or
      have several pre-installation requirements. This led us to develop an analysis
      workflow for analysing differential splicing using freely available software
      packages that are already being widely used for gene expression analysis. The
      workflow uses the packages in the standard installation of R and Bioconductor
      (BiocLite) to identify differential splicing. We use the splice index method with
      the LIMMA framework. The main drawback with this approach is that it relies on
      accurate estimates of gene expression from the probe-level data. Methods such as
      RMA and PLIER may misestimate when a large proportion of exons are spliced. We
      therefore present the novel concept of a gene correlation coefficient calculated
      using only the probeset expression pattern within a gene. We show that genes with
      lower correlation coefficients are likely to be differentially spliced. RESULTS:
      The LIMMA approach was used to identify several tissue-specific transcripts and
      splicing events that are supported by previous experimental studies. Filtering
      the data is necessary, particularly removing exons and genes that are not
      expressed in all samples and cross-hybridising probesets, in order to reduce the
      false positive rate. The LIMMA approach ranked genes containing single or few
      differentially spliced exons much higher than genes containing several
      differentially spliced exons. On the other hand we found the gene correlation
      coefficient approach better for identifying genes with a large number of
      differentially spliced exons. CONCLUSION: We show that LIMMA can be used to
      identify differential exon splicing from Affymetrix exon array data. Though
      further work would be necessary to develop the use of correlation coefficients
      into a complete analysis approach, the preliminary results demonstrate their
      usefulness for identifying differentially spliced genes. The two approaches work
      complementary as they can potentially identify different subsets of genes
      (single/few spliced exons vs. large transcript structure differences).

PMID- 19154579
TI  - The effects of small-scale, homelike facilities for older people with dementia on
      residents, family caregivers and staff: design of a longitudinal, quasi
      experimental study.
AB  - BACKGROUND: Small-scale and homelike facilities for older people with dementia
      are rising in current dementia care. In these facilities, a small number of
      residents live together and form a household with staff. Normal, daily life and
      social participation are emphasized. It is expected that these facilities improve
      residents' quality of life. Moreover, it may have a positive influence on staff's
      job satisfaction and families involvement and satisfaction with care. However,
      effects of these small-scale and homelike facilities have hardly been
      investigated. Since the number of people with dementia increases, and
      institutional long-term care is more and more organized in small-scale and
      homelike facilities, more research into effects is necessary. This paper presents
      the design of a study investigating effects of small-scale living facilities in
      the Netherlands on residents, family caregivers and nursing staff. METHODS AND
      DESIGN: A longitudinal, quasi-experimental study is carried out, in which 2
      dementia care settings are compared: small-scale living facilities and regular
      psychogeriatric wards in traditional nursing homes. Data is collected from
      residents, their family caregivers and nursing staff at baseline and after 6 and
      12 months of follow-up. Approximately 2 weeks prior to baseline measurement,
      residents are screened on cognition and activities of daily living (ADL). Based
      on this screening profile, residents in psychogeriatric wards are matched to
      residents living in small-scale living facilities. The primary outcome measure
      for residents is quality of life. In addition, neuropsychiatric symptoms,
      depressive symptoms and social engagement are assessed. Involvement with care,
      perceived burden and satisfaction with care provision are primary outcome
      variables for family caregivers. The primary outcomes for nursing staff are job
      satisfaction and motivation. Furthermore, job characteristics social support,
      autonomy and workload are measured. A process evaluation is performed to
      investigate to what extent small-scale living facilities and psychogeriatric
      wards are designed as they were intended. In addition, participants' satisfaction
      and experiences with small-scale living facilities are investigated. DISCUSSION:
      A longitudinal, quasi-experimental study is presented to investigate effects of
      small-scale living facilities. Although some challenges concerning this design
      exist, it is currently the most feasible method to assess effects of this
      relatively new dementia care setting.

PMID- 19154580
TI  - Cerebral microdialysis for detection of bacterial meningitis in aneurysmal
      subarachnoid hemorrhage patients: a cohort study.
AB  - INTRODUCTION: Bacterial meningitis (BM) is a severe complication in patients with
      aneurysmal subarachnoid haemorrhage (SAH). Clinical signs of meningitis are often
      masked by SAH-related symptoms, and routine cerebrospinal fluid (CSF) analysis
      fails to indicate BM. Microdialysis (MD) is a technique for monitoring cerebral
      metabolism in patients with SAH. A cohort study was performed to investigate the
      value of MD for the diagnosis of BM. METHODS: Retrospectively, 167 patients with
      SAH in an ongoing investigation on cerebral metabolism monitored by MD were
      analysed for the presence of BM and related MD changes. Diagnosis of BM was based
      on microbiological CSF culture or clinical symptoms responding to antibiotic
      treatment, combined with an increased CSF cell count and/or fever. Levels of MD
      parameters before and after diagnosis of BM were analysed and compared with the
      spontaneous course in controls. RESULTS: BM developed in 20 patients, of which 12
      underwent MD monitoring at the time of diagnosis. A control group was formed
      using 147 patients with SAH not developing meningitis. On the day BM was
      diagnosed, cerebral glucose was lower compared with the value three days before
      (p = 0.012), and the extent of decrease was significantly higher than in controls
      (p = 0.044). A decrease in cerebral glucose by 1 mmol/L combined with the
      presence of fever >or= 38 degrees C indicated BM with a sensitivity of 69% and a
      specificity of 80%. CSF chemistry failed to indicate BM, but the cell count
      increased during the days before diagnosis (p < 0.05). CONCLUSIONS: A decrease in
      MD glucose combined with the presence of fever detected BM with acceptable
      sensitivity and specificity, while CSF chemistry failed to indicate BM. In
      patients with SAH where CSF cell count is not available or helpful, MD might
      serve as an adjunct criterion for early diagnosis of BM.

PMID- 19154576
TI  - Antiphospholipid antibodies: paradigm in transition.
AB  - OBJECTIVES: This is a critical review of anti-phospholipid antibodies (aPL). Most
      prior reviews focus on the aPL syndrome (APS), a thrombotic condition often
      marked by neurological disturbance. We bring to attention recent evidence that
      aPL may be equally relevant to non-thrombotic autoimmune conditions, notably,
      multiple sclerosis and ITP. ORGANIZATION: After a brief history, the recent
      proliferation of aPL target antigens is reviewed. The implication is that many
      more exist. Theories of aPL in thrombosis are then reviewed, concluding that all
      have merit but that aPL may have more diverse pathological consequences than now
      recognized. Next, conflicting results are explained by methodological
      differences. The lupus anticoagulant (LA) is then discussed. LA is the best
      predictor of thrombosis, but why this is true is not settled. Finally, aPL in non
      thrombotic disorders is reviewed. CONCLUSION: The current paradigm of aPL holds
      that they are important in thrombosis, but they may have much wider clinical
      significance, possibly of special interest in neurology.

PMID- 19154581
TI  - Surgical and medical emergencies on board European aircraft: a retrospective
      study of 10189 cases.
AB  - INTRODUCTION: In-flight medical and surgical emergencies (IMEs) onboard
      commercial aircrafts occur quite commonly. However, little epidemiological
      research exists concerning these incidents. METHODS: Thirty-two European airlines
      were asked to provide anonymous data on medical flight reports of IMEs for the
      years 2002 to 2007. The total number of incidents was correlated to revenue
      passenger kilometers (rpk). Additionally, on-board births and deaths, flight
      diversions, flight routes (continental/intercontinental) and involvement of a
      physician or medical professional in providing therapy were analysed. RESULTS:
      Only four airlines, of which two participated in this study, were able to provide
      the necessary data. A total of 10,189 cases of IMEs were analysed. Syncope was
      the most common medical condition reported (5307 cases, 53.5%) followed by
      gastrointestinal disorders (926 cases, 8.9%) and cardiac conditions (509 cases,
      4.9%). The most common surgical conditions were thrombosis (47 cases, 0.5%) and
      appendicitis (27 cases, 0.25%). In 2.8% of all IMEs, an aircraft diversion was
      performed. In 86% of cases, a physician or medical professional was involved in
      providing therapy. A mean (standard deviation) of 14 (+/- 2.3, 10.8 to 16.6
      interquartile range) IMEs per billion rpk was calculated. CONCLUSIONS: The study
      demonstrates that although aviation is regulated by a variety of national and
      international laws, standardised documentation of IMEs is inadequate and needs
      further development.

PMID- 19154582
TI  - Simultaneous analysis of distinct Omics data sets with integration of biological
      knowledge: Multiple Factor Analysis approach.
AB  - BACKGROUND: Genomic analysis will greatly benefit from considering in a global
      way various sources of molecular data with the related biological knowledge. It
      is thus of great importance to provide useful integrative approaches dedicated to
      ease the interpretation of microarray data. RESULTS: Here, we introduce a data
      mining approach, Multiple Factor Analysis (MFA), to combine multiple data sets
      and to add formalized knowledge. MFA is used to jointly analyse the structure
      emerging from genomic and transcriptomic data sets. The common structures are
      underlined and graphical outputs are provided such that biological meaning
      becomes easily retrievable. Gene Ontology terms are used to build gene modules
      that are superimposed on the experimentally interpreted plots. Functional
      interpretations are then supported by a step-by-step sequence of graphical
      representations. CONCLUSION: When applied to genomic and transcriptomic data and
      associated Gene Ontology annotations, our method prioritize the biological
      processes linked to the experimental settings. Furthermore, it reduces the time
      and effort to analyze large amounts of 'Omics' data.

PMID- 19154584
TI  - CT appearance of a patent impar umbilical artery in an adult woman and related
      anomalies: a case report and review of the literature.
AB  - BACKGROUND: We report on a case of an impar umbilical artery (IUA) in an 18-year
      old woman. CASE PRESENTATION: The aorta branched off at level L2 into a ventral
      IUA and a dorsal aorta. The strong IUA produced the inferior mesenteric artery
      (IMA), the renal artery of a left-sided duplex kidney, and the right-sided
      ovarian artery before it turned to the right to merge into the right common iliac
      artery. From the aorta arose the lumbar arteries, the median sacral artery,
      lateral sacral arteries, and iliolumbar arteries before it turned to the left.
      Both vessels were connected by an artery 0.8 cm in diameter running
      infraperitoneal, from the left side of which the uterine artery arose for a left
      paramedian uterus didelphys. CONCLUSION: This anatomical situation is presented
      for the first time using an arterial contrast enhanced CT and is discussed within
      the context of previously known cases.

PMID- 19154585
TI  - Microsatellite instability in colorectal cancer and association with thymidylate
      synthase and dihydropyrimidine dehydrogenase expression.
AB  - BACKGROUND: Microsatellite instability (MSI) refers to mutations in short motifs
      of tandemly repeated nucleotides resulting from replication errors and deficient
      mismatch repair (MMR). Colorectal cancer with MSI has characteristic biology and
      chemosensitivity, however the molecular basis remains unclarified. The
      association of MSI and MMR status with outcome and with thymidylate synthase (TS)
      and dihydropyrimidine dehydrogenase (DPD) expression in colorectal cancer were
      evaluated. METHODS: MSI in five reference loci, MMR enzymes (hMSH2, hMSH6, hMLH1
      and hPMS2), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD)
      expression were assessed in paraffin embedded tumor specimens, and associated
      with outcome in 340 consecutive patients completely resected for colorectal
      cancer stages II-IV and subsequently receiving adjuvant 5-fluorouracil therapy.
      RESULTS: MSI was found in 43 (13.8%) tumors. Absence of repair protein expression
      was assessed in 52 (17.0%) tumors, which had primarily lost hMLH1 in 39 (12.7%),
      hMSH2 in 5 (1.6%), and hMSH6 in 8 (2.6%) tumors. In multivariate analysis MSI
      (instable) compared to MSS (stable) tumors were significantly associated with
      lower risk of recurrence (hazard ratio (HR) = 0.3; 95% CI: 0.2-0.7; P = 0.0007)
      and death (HR = 0.4; 95% CI: 0.2-0.9; P = 0.02) independently of the TS and DPD
      expressions. A direct relationship between MSI and TS intensity (P = 0.001) was
      found, while there was no significant association with DPD intensity (P = 0.1).
      CONCLUSION: The favourable outcome of MSI colorectal carcinomas is ascribed
      mainly to the tumor biology and to a lesser extent to antitumor response to 5
      fluorouracil therapy. There is no evidence that differential TS or DPD expression
      may account for these outcome characteristics.

PMID- 19154586
TI  - Behavioral and brain pattern differences between acting and observing in an
      auditory task.
AB  - BACKGROUND: Recent research has shown that errors seem to influence the patterns
      of brain activity. Additionally current notions support the idea that similar
      brain mechanisms are activated during acting and observing. The aim of the
      present study was to examine the patterns of brain activity of actors and
      observers elicited upon receiving feedback information of the actor's response.
      METHODS: The task used in the present research was an auditory identification
      task that included both acting and observing settings, ensuring concurrent ERP
      measurements of both participants. The performance of the participants was
      investigated in conditions of varying complexity. ERP data were analyzed with
      regards to the conditions of acting and observing in conjunction to correct and
      erroneous responses. RESULTS: The obtained results showed that the complexity
      induced by cue dissimilarity between trials was a demodulating factor leading to
      poorer performance. The electrophysiological results suggest that feedback
      information results in different intensities of the ERP patterns of observers and
      actors depending on whether the actor had made an error or not. The LORETA source
      localization method yielded significantly larger electrical activity in the
      supplementary motor area (Brodmann area 6), the posterior cingulate gyrus
      (Brodmann area 31/23) and the parietal lobe (Precuneus/Brodmann area 7/5).
      CONCLUSION: These findings suggest that feedback information has a different
      effect on the intensities of the ERP patterns of actors and observers depending
      on whether the actor committed an error. Certain neural systems, including medial
      frontal area, posterior cingulate gyrus and precuneus may mediate these
      modulating effects. Further research is needed to elucidate in more detail the
      neuroanatomical and neuropsychological substrates of these systems.

PMID- 19154587
TI  - Barriers to healthcare utilization in fatiguing illness: a population-based study
      in Georgia.
AB  - BACKGROUND: The purpose of this study was to determine the prevalence of barriers
      to healthcare utilization in persons with fatiguing illness and describe its
      association with socio-demographics, the number of health conditions, and
      frequency of healthcare utilization. Furthermore, we sought to identify what
      types of barriers interfered with healthcare utilization and why they occurred.
      METHODS: In a cross-sectional population-based survey, 780 subjects, 112 of them
      with chronic fatigue syndrome (CFS), completed a healthcare utilization
      questionnaire. Text analysis was used to create the emerging themes from verbatim
      responses regarding barriers to healthcare utilization. Multiple logistic
      regression was performed to examine the association between barriers to
      healthcare utilization and other factors. RESULTS: Forty percent of subjects
      reported at least one barrier to healthcare utilization. Of 112 subjects with
      CFS, 55% reported at least one barrier to healthcare utilization. Fatiguing
      status, reported duration of fatigue, insurance, and BMI were significant risk
      factors for barriers to healthcare utilization. After adjusting for socio
      demographics, medication use, the number of health problems, and frequency of
      healthcare utilization, fatiguing status remained significantly associated with
      barriers to healthcare utilization. Subjects with CFS were nearly 4 times more
      likely to forego needed healthcare during the preceding year than non-fatigued
      subjects while those with insufficient fatigue (ISF) were nearly 3 times more
      likely.Three domains emerged from text analysis on barriers to healthcare
      utilization: 1) accessibility; 2) knowledge-attitudes-beliefs (KABs); and, 3)
      healthcare system. CFS and reported duration of fatigue were significantly
      associated with each of these domains. Persons with CFS reported high levels of
      healthcare utilization barriers for each domain: accessibility (34%), healthcare
      system (25%), and KABs (19%). In further examination of barrier domains to
      healthcare utilization, compared to non-fatigued persons adjusted ORs for CFS
      having "accessibility", "KAB" and "Healthcare System" barrier domains decreased
      by 40%, 30%, and 19%, respectively. CONCLUSION: Barriers to healthcare
      utilization pose a significant problem in persons with fatiguing illnesses. Study
      results suggested two-fold implications: a symptom-targeted model focusing on
      symptoms associated with fatigue; and an interactive model requiring efforts from
      patients and providers to improve interactions between them by reducing barriers
      in accessibility, KABs, and healthcare system.

PMID- 19154588
TI  - Systematic review of effect of community-level interventions to reduce maternal
      mortality.
AB  - BACKGROUND: The objective was to provide a systematic review of the effectiveness
      of community-level interventions to reduce maternal mortality. METHODS: We
      searched published papers using Medline, Embase, Cochrane library, CINAHL, BNI,
      CAB ABSTRACTS, IBSS, Web of Science, LILACS and African Index Medicus from
      inception or at least 1982 to June 2006; searched unpublished works using
      National Research Register website, metaRegister and the WHO International Trial
      Registry portal. We hand searched major references.Selection criteria were
      maternity or childbearing age women, comparative study designs with concurrent
      controls, community-level interventions and maternal death as an outcome. We
      carried out study selection, data abstraction and quality assessment
      independently in duplicate. RESULTS: We found five cluster randomised controlled
      trials (RCT) and eight cohort studies of community-level interventions. We
      summarised results as odds ratios (OR) and confidence intervals (CI), combined
      using the Peto method for meta-analysis. Two high quality cluster RCTs, aimed at
      improving perinatal care practices, showed a reduction in maternal mortality
      reaching statistical significance (OR 0.62, 95% CI 0.39 to 0.98). Three
      equivalence RCTs of minimal goal-oriented versus usual antenatal care showed no
      difference in maternal mortality (1.09, 95% CI 0.53 to 2.25). The cohort studies
      were of low quality and did not contribute further evidence. CONCLUSION:
      Community-level interventions of improved perinatal care practices can bring
      about a reduction in maternal mortality. This challenges the view that investment
      in such interventions is not worthwhile. Programmes to improve maternal mortality
      should be evaluated using randomised controlled techniques to generate further
      evidence.

PMID- 19154589
TI  - Value of ultrasound-guided irrigation and drainage of refractory pyocysts in
      ADPKD.
AB  - BACKGROUND: Cyst infections is not common in the patients with autosomal dominant
      polycystic kidney disease (ADPKD) however it may pose major problems to the
      clinicians because the diagnosis is hampered by lack of reliable imaging
      techniques for identification of the infected cysts and treatment may be
      difficult due to poor penetration of antibiotics into the cysts. CASE
      PRESENTATION: We present a case of ADPKD and intractable pyocysts that did not
      respond to standard antibiotic therapy but successfully treated by using
      ultrasound-guided cyst puncture, and repeated irrigation and drainage.
      CONCLUSION: Where the experienced interventional radiologists are available, this
      method can rescue these patients from nephrectomy.

PMID- 19154590
TI  - Combining Pareto-optimal clusters using supervised learning for identifying co
      expressed genes.
AB  - BACKGROUND: The landscape of biological and biomedical research is being changed
      rapidly with the invention of microarrays which enables simultaneous view on the
      transcription levels of a huge number of genes across different experimental
      conditions or time points. Using microarray data sets, clustering algorithms have
      been actively utilized in order to identify groups of co-expressed genes. This
      article poses the problem of fuzzy clustering in microarray data as a
      multiobjective optimization problem which simultaneously optimizes two internal
      fuzzy cluster validity indices to yield a set of Pareto-optimal clustering
      solutions. Each of these clustering solutions possesses some amount of
      information regarding the clustering structure of the input data. Motivated by
      this fact, a novel fuzzy majority voting approach is proposed to combine the
      clustering information from all the solutions in the resultant Pareto-optimal
      set. This approach first identifies the genes which are assigned to some
      particular cluster with high membership degree by most of the Pareto-optimal
      solutions. Using this set of genes as the training set, the remaining genes are
      classified by a supervised learning algorithm. In this work, we have used a
      Support Vector Machine (SVM) classifier for this purpose. RESULTS: The
      performance of the proposed clustering technique has been demonstrated on five
      publicly available benchmark microarray data sets, viz., Yeast Sporulation, Yeast
      Cell Cycle, Arabidopsis Thaliana, Human Fibroblasts Serum and Rat Central Nervous
      System. Comparative studies of the use of different SVM kernels and several
      widely used microarray clustering techniques are reported. Moreover, statistical
      significance tests have been carried out to establish the statistical superiority
      of the proposed clustering approach. Finally, biological significance tests have
      been carried out using a web based gene annotation tool to show that the proposed
      method is able to produce biologically relevant clusters of co-expressed genes.
      CONCLUSION: The proposed clustering method has been shown to perform better than
      other well-known clustering algorithms in finding clusters of co-expressed genes
      efficiently. The clusters of genes produced by the proposed technique are also
      found to be biologically significant, i.e., consist of genes which belong to the
      same functional groups. This indicates that the proposed clustering method can be
      used efficiently to identify co-expressed genes in microarray gene expression
      data.Supplementary Website The pre-processed and normalized data sets, the matlab
      code and other related materials are available at
      http://anirbanmukhopadhyay.50webs.com/mogasvm.html.

PMID- 19154591
TI  - Congenital lobar emphysema: a case report.
AB  - Congenital lobar emphysema is a rare variety of congenital malformation of lung
      characterized by over distension of a lobe of a lung due to partial obstruction
      of the bronchus. We are reporting a neonate admitted in the pediatric emergency
      ward with the respiratory distress since 16th day of life.Investigation revealed
      the overexpansion of the left upper lobe with mediastinal herniation, shifting of
      the mediastinum to the opposite side and collapse of the ipsilateral lower lobe.
      The baby was treated with conservative treatment and the condition of the baby
      was improved.

PMID- 19154592
TI  - Inhibition of lentivirus replication by aqueous extracts of Prunella vulgaris.
AB  - BACKGROUND: Various members of the mint family have been used historically in
      Chinese and Native American medicine. Many of these same family members,
      including Prunella vulgaris, have been reported to have anti-viral activities. To
      further characterize the anti-lentiviral activities of P. vulgaris, water and
      ethanol extractions were tested for their ability to inhibit equine infectious
      anemia virus (EIAV) replication. RESULTS: Aqueous extracts contained more anti
      viral activity than did ethanol extracts, displaying potent anti-lentiviral
      activity against virus in cell lines as well as in primary cell cultures with
      little to no cellular cytotoxicity. Time-of-addition studies demonstrated that
      the extracts were effective when added during the first four h of the viral life
      cycle, suggesting that the botanical constituents were targeting the virion
      itself or early entry events. Further analysis revealed that the extracts did not
      destroy EIAV virion integrity, but prevented viral particles from binding to the
      surface of permissive cells. Modest levels of anti-EIAV activity were also
      detected when the cells were treated with the extracts prior to infection,
      indicating that anti-EIAV botanical constituents could interact with both viral
      particles and permissive cells to interfere with infectivity. Size fractionation
      of the extract demonstrated that eight of the nine fractions generated from
      aqueous extracts displayed anti-viral activity. Separation of ethanol soluble and
      insoluble compounds in the eight active fractions revealed that ethanol-soluble
      constituents were responsible for the anti-viral activity in one fraction whereas
      ethanol-insoluble constituents were important for the anti-viral activity in two
      of the other fractions. In three of the five fractions that lost activity upon
      sub-fractionation, anti-viral activity was restored upon reconstitution of the
      fractions, indicating that synergistic anti-viral activity is present in several
      of the fractions. CONCLUSION: Our findings indicate that multiple Prunella
      constituents have profound anti-viral activity against EIAV, providing additional
      evidence of the broad anti-viral abilities of these extracts. The ability of the
      aqueous extracts to prevent entry of viral particles into permissive cells
      suggests that these extracts may function as promising microbicides against
      lentiviruses.

PMID- 19154593
TI  - Rupture and intra-peritoneal bleeding of a hepatocellular carcinoma after a
      transarterial chemoembolization procedure: a case report.
AB  - BACKGROUND: Transarterial chemoembolization (TACE) is a well accepted treatment
      for inoperable hepatocellular carcinoma (HCC). While minor complications involve
      10% of all patients, severe complications are rare. CASE PRESENTATION: We
      describe a case of a 90-year-old male with a large, superficial HCC who underwent
      TACE. He had a significant intraperitoneal bleed secondary to tumor rupture
      immediately following the procedure. CONCLUSION: Tumor size and superficial
      location must be considered risk factors for tumor rupture and related
      complications.

PMID- 19154594
TI  - Horizontal gene transfer between Wolbachia and the mosquito Aedes aegypti.
AB  - BACKGROUND: The evolutionary importance of horizontal gene transfer (HGT) from
      Wolbachia endosymbiotic bacteria to their eukaryotic hosts is a topic of
      considerable interest and debate. Recent transfers of genome fragments from
      Wolbachia into insect chromosomes have been reported, but it has been argued that
      these fragments may be on an evolutionary trajectory to degradation and loss.
      RESULTS: We have discovered a case of HGT, involving two adjacent genes, between
      the genomes of Wolbachia and the currently Wolbachia-uninfected mosquito Aedes
      aegypti, an important human disease vector. The lower level of sequence identity
      between Wolbachia and insect, the transcription of all the genes involved, and
      the fact that we have identified homologs of the two genes in another Aedes
      species (Ae. mascarensis), suggest that these genes are being expressed after an
      extended evolutionary period since horizontal transfer, and therefore that the
      transfer has functional significance. The association of these genes with
      Wolbachia prophage regions also provides a mechanism for the transfer.
      CONCLUSION: The data support the argument that HGT between Wolbachia
      endosymbiotic bacteria and their hosts has produced evolutionary innovation.

PMID- 19154595
TI  - SNAVI: Desktop application for analysis and visualization of large-scale
      signaling networks.
AB  - BACKGROUND: Studies of cellular signaling indicate that signal transduction
      pathways combine to form large networks of interactions. Viewing protein-protein
      and ligand-protein interactions as graphs (networks), where biomolecules are
      represented as nodes and their interactions are represented as links, is a
      promising approach for integrating experimental results from different sources to
      achieve a systematic understanding of the molecular mechanisms driving cell
      phenotype. The emergence of large-scale signaling networks provides an
      opportunity for topological statistical analysis while visualization of such
      networks represents a challenge. RESULTS: SNAVI is Windows-based desktop
      application that implements standard network analysis methods to compute the
      clustering, connectivity distribution, and detection of network motifs, as well
      as provides means to visualize networks and network motifs. SNAVI is capable of
      generating linked web pages from network datasets loaded in text format. SNAVI
      can also create networks from lists of gene or protein names. CONCLUSION: SNAVI
      is a useful tool for analyzing, visualizing and sharing cell signaling data.
      SNAVI is open source free software. The installation may be downloaded from:
      http://snavi.googlecode.com. The source code can be accessed from:
      http://snavi.googlecode.com/svn/trunk.

PMID- 19154597
TI  - Cutaneous mastocytosis. Getting beneath the skin of the issue: a case report.
AB  - An eleven month old girl presented with chronic urticaria since three months of
      age. There was a generalised hyperpigmented maculo-papular rash. Darier sign was
      positive. The skin biopsy showed plenty of spindle shaped mast cells with
      eosinophilic cytoplasm infiltrating the dermis and the appendiceal structures.
      The diagnosis of cutaneous mastocytosis (urticaria pigmentosa) was made. The
      child received symptomatic relief with chronic oral hydroxyzine and ranitidine
      therapy. Automated epinephrine self-injectors usually prescribed in this
      condition for self-management of anaphylactic episodes were not available.
      Intramuscular administration of (1:1000) diluted adrenaline via a disposable
      tuberculin syringe was taught to the mother. A medical bracelet containing her
      diagnosis and instructions in emergency was custom-made for her.

PMID- 19154596
TI  - Transcriptomic and metabolomic profiling of Zymomonas mobilis during aerobic and
      anaerobic fermentations.
AB  - BACKGROUND: Zymomonas mobilis ZM4 (ZM4) produces near theoretical yields of
      ethanol with high specific productivity and recombinant strains are able to
      ferment both C-5 and C-6 sugars. Z. mobilis performs best under anaerobic
      conditions, but is an aerotolerant organism. However, the genetic and
      physiological basis of ZM4's response to various stresses is understood poorly.
      RESULTS: In this study, transcriptomic and metabolomic profiles for ZM4 aerobic
      and anaerobic fermentations were elucidated by microarray analysis and by high
      performance liquid chromatography (HPLC), gas chromatography (GC) and gas
      chromatography-mass spectrometry (GC-MS) analyses. In the absence of oxygen, ZM4
      consumed glucose more rapidly, had a higher growth rate, and ethanol was the
      major end-product. Greater amounts of other end-products such as acetate,
      lactate, and acetoin were detected under aerobic conditions and at 26 h there was
      only 1.7% of the amount of ethanol present aerobically as there was
      anaerobically. In the early exponential growth phase, significant differences in
      gene expression were not observed between aerobic and anaerobic conditions via
      microarray analysis. HPLC and GC analyses revealed minor differences in
      extracellular metabolite profiles at the corresponding early exponential phase
      time point. Differences in extracellular metabolite profiles between conditions
      became greater as the fermentations progressed. GC-MS analysis of stationary
      phase intracellular metabolites indicated that ZM4 contained lower levels of
      amino acids such as alanine, valine and lysine, and other metabolites like
      lactate, ribitol, and 4-hydroxybutanoate under anaerobic conditions relative to
      aerobic conditions. Stationary phase microarray analysis revealed that 166 genes
      were significantly differentially expressed by more than two-fold. Transcripts
      for Entner-Doudoroff (ED) pathway genes (glk, zwf, pgl, pgk, and eno) and gene
      pdc, encoding a key enzyme leading to ethanol production, were at least 30-fold
      more abundant under anaerobic conditions in the stationary phase based on
      quantitative-PCR results. We also identified differentially expressed ZM4 genes
      predicted by The Institute for Genomic Research (TIGR) that were not predicted in
      the primary annotation. CONCLUSION: High oxygen concentrations present during Z.
      mobilis fermentations negatively influence fermentation performance. The maximum
      specific growth rates were not dramatically different between aerobic and
      anaerobic conditions, yet oxygen did affect the physiology of the cells leading
      to the buildup of metabolic byproducts that ultimately led to greater differences
      in transcriptomic profiles in stationary phase.

PMID- 19154598
TI  - Antiviral prophylaxis during pandemic influenza may increase drug resistance.
AB  - BACKGROUND: Neuraminidase inhibitors (NI) and social distancing play a major role
      in plans to mitigate future influenza pandemics. METHODS: Using the freely
      available program InfluSim, the authors examine to what extent NI-treatment and
      prophylaxis promote the occurrence and transmission of a NI resistant strain.
      RESULTS: Under a basic reproduction number of R0 = 2.5, a NI resistant strain can
      only spread if its transmissibility (fitness) is at least 40% of the fitness of
      the drug-sensitive strain. Although NI drug resistance may emerge in treated
      patients in such a late state of their disease that passing on the newly
      developed resistant viruses is unlikely, resistant strains quickly become highly
      prevalent in the population if their fitness is high. Antiviral prophylaxis
      further increases the pressure on the drug-sensitive strain and favors the spread
      of resistant infections. The authors show scenarios where pre-exposure antiviral
      prophylaxis even increases the number of influenza cases and deaths. CONCLUSION:
      If the fitness of a NI resistant pandemic strain is high, any use of prophylaxis
      may increase the number of hospitalizations and deaths in the population. The use
      of neuraminidase inhibitors should be restricted to the treatment of cases
      whereas prophylaxis should be reduced to an absolute minimum in that case.

PMID- 19154599
TI  - Traffic-related air pollution associated with prevalence of asthma and
      COPD/chronic bronchitis. A cross-sectional study in Southern Sweden.
AB  - BACKGROUND: There is growing evidence that air pollution from traffic has adverse
      long-term effects on chronic respiratory disease in children, but there are few
      studies and more inconclusive results in adults. We examined associations between
      residential traffic and asthma and COPD in adults in southern Sweden. A postal
      questionnaire in 2000 (n = 9319, 18-77 years) provided disease status, and self
      reported exposure to traffic. A Geographical Information System (GIS) was used to
      link geocoded residential addresses to a Swedish road database and an emission
      database for NOx. RESULTS: Living within 100 m of a road with >10 cars/minute
      (compared with having no heavy road within this distance) was associated with
      prevalence of asthma diagnosis (OR = 1.40, 95% CI = 1.04-1.89), and COPD
      diagnosis (OR = 1.64, 95%CI = 1.11-2.4), as well as asthma and chronic bronchitis
      symptoms. Self-reported traffic exposure was associated with asthma diagnosis and
      COPD diagnosis, and with asthma symptoms. Annual average NOx was associated with
      COPD diagnosis and symptoms of asthma and chronic bronchitis. CONCLUSION: Living
      close to traffic was associated with prevalence of asthma diagnosis, COPD
      diagnosis, and symptoms of asthma and bronchitis. This indicates that traffic
      related air pollution has both long-term and short-term effects on chronic
      respiratory disease in adults, even in a region with overall low levels of air
      pollution.

PMID- 19154600
TI  - HIS-based electronic documentation can significantly reduce the time from biopsy
      to final report for prostate tumours and supports quality management as well as
      clinical research.
AB  - BACKGROUND: Timely and accurate information is important to guide the medical
      treatment process. We developed, implemented and assessed an order-entry system
      to support documentation of prostate histologies involving urologists,
      pathologists and physicians in private practice. METHODS: We designed electronic
      forms for histological prostate biopsy reports in our hospital information system
      (HIS). These forms are created by urologists and sent electronically to
      pathologists. Pathological findings are entered into the system and sent back to
      the urologists. We assessed time from biopsy to final report (TBF) and compared
      pre-implementation phase (paper-based forms) and post-implementation phase. In
      addition we analysed completeness of the electronic data. RESULTS: We compared 87
      paper-based with 86 electronic cases. Using electronic forms within the HIS
      decreases time span from biopsy to final report by more than one day per patient
      (p < 0.0001). Beyond the optimized workflow we observed a good acceptance because
      physicians were already familiar with the HIS. The possibility to use these
      routine data for quality management and research purposes is an additional
      important advantage of the electronic system. CONCLUSION: Electronic
      documentation can significantly reduce the time from biopsy to final report of
      prostate biopsy results and generates a reliable basis for quality management and
      research purposes.

PMID- 19154601
TI  - Choroidal eye metastases from (recurrent) primary peritoneal carcinoma: case
      report and review of the literature.
AB  - BACKGROUND: Choroidal metastases from gynaecological primary are extremely rare.
      There is no documented case in the literature of choroid metastasis in a patient
      with primary peritoneal carcinoma (PPC). METHODS & RESULTS: We describe the first
      case of a 54-year-old woman with a history of borderline mucinous tumour who
      presented 17 months later with PPC and 21 months after with recurrent disease
      metastatic to the eye, and review pertinent literature. CONCLUSION: High index of
      suspicion is warranted when patients with history of primary peritoneal carcinoma
      present with visual complaints in order to treat and/or relieve symptomatology
      from metastatic eye disease.

PMID- 19154602
TI  - Novel concepts in virally induced asthma.
AB  - Viruses are the predominant infectious cause of asthma exacerbations in the
      developed world. In addition, recent evidence strongly suggests that viral
      infections may also have a causal role in the development of childhood asthma. In
      this article, we will briefly describe the general perception of how the link
      between infections and asthma has changed over the last century, and then focus
      on very recent developments that have provided new insights into the contribution
      of viruses to asthma pathogenesis. Highlighted areas include the contribution of
      severe early life viral infections to asthma inception, genetic determinants of
      severe viral infections in infancy, the differences in innate and adaptive immune
      system cytokine responses to viral infection between asthmatic and nonasthmatic
      subjects, and a potential vaccine strategy to prevent severe early life virally
      induced illness.

PMID- 19154603
TI  - Effective carbon partitioning driven by exotic phloem-specific regulatory
      elements fused to the Arabidopsis thaliana AtSUC2 sucrose-proton symporter gene.
AB  - BACKGROUND: AtSUC2 (At1g22710) from Arabidopsis thaliana encodes a phloem
      localized sucrose/proton symporter required for efficient photoassimilate
      transport from source tissues to sink tissues. AtSUC2 plays a key role in
      coordinating the demands of sink tissues with the output capacity of source
      leaves, and in maintaining phloem hydrostatic pressure during changes in plant
      water balance. Expression and activity are regulated, both positively and
      negatively, by developmental (sink to source transition) and environmental cues,
      including light, diurnal changes, photoassimilate levels, turgor pressure,
      drought and osmotic stress, and hormones. RESULTS: To assess the importance of
      this regulation to whole-plant growth and carbon partitioning, AtSUC2 cDNA was
      expressed from two exotic, phloem-specific promoters in a mutant background
      debilitated for AtSUC2 function. The first was a promoter element from Commelina
      Yellow Mottle Virus (CoYMV), and the second was the rolC promoter from
      Agrobacterium rhizogenes. CoYMVp::AtSUC2 cDNA restored growth and carbon
      partitioning to near wild-type levels, whereas plants harboring rolCp::AtSUC2
      cDNA showed only partial complementation. CONCLUSION: Expressing AtSUC2 cDNA from
      exotic, phloem-specific promoters argues that strong, phloem-localized expression
      is sufficient for efficient transport. Expressing AtSUC2 from promoters that
      foster efficient phloem transport but are subject to regulatory cascades
      different from the endogenous sucrose/proton symporter genes has implications for
      biotechnology.

PMID- 19154604
TI  - TRACE (Trunk Aesthetic Clinical Evaluation), a routine clinical tool to evaluate
      aesthetics in scoliosis patients: development from the Aesthetic Index (AI) and
      repeatability.
AB  - BACKGROUND: Aesthetic appearance is of primary importance in the treatment of
      adolescent idiopathic scoliosis (AIS), but to date tools for routine clinical
      practice have not become available. The aim of the present study is to develop
      such a tool and to verify its repeatability. METHODS:  INSTRUMENTATION: At first
      we developed the Aesthetic Index (AI), based on a three-point scale for asymmetry
      of the shoulders, scapulae and waist that we tested for 5 years. From this
      experience we developed another tool we called TRACE, the acronym of Trunk
      Aesthetic Clinical Evaluation; TRACE is a 12-point scale based on four sub
      scales, shoulders (0-3), scapulae (0-2), hemi-thorax (0-2) and waist (0-4).
      POPULATION: Posterior-anterior (PA) photographs of one hundred-sixty AIS
      patients. PROCEDURES: Each photograph was scored in two independent tests by four
      observers using AI, and subsequently TRACE. DATA ANALYSIS: Kappa statistical
      analysis and 95% level of agreement were used; we also identified the minimum
      significant change (95% confidence level). RESULTS: We found the intra- and inter
      raters repeatability of AI to be fair. Three points out of seven was the minimum
      significant change between two different evaluations. For TRACE, intra-rater
      repeatability was fair and inter-raters poor; but the minimum significant change
      was three (intra-rater), or four (inter-raters) out of twelve points. CONCLUSION:
      Widening the scale from 7 (AI) to 12 points (TRACE) increased the clinical
      sensitivity to changes of the aesthetic scale, even if TRACE has only a fair
      repeatability. TRACE is a no-cost tool for routine clinical practice in AIS
      patients. Due to the absence of other comparable validated tools, once the
      inherent measurement error is known and understood, its routine clinical use by
      physicians is advised.

PMID- 19154605
TI  - Domain duplication, divergence, and loss events in vertebrate Msx paralogs reveal
      phylogenomically informed disease markers.
AB  - BACKGROUND: Msx originated early in animal evolution and is implicated in human
      genetic disorders. To reconstruct the functional evolution of Msx and inform the
      study of human mutations, we analyzed the phylogeny and synteny of 46 metazoan
      Msx proteins and tracked the duplication, diversification and loss of conserved
      motifs. RESULTS: Vertebrate Msx sequences sort into distinct Msx1, Msx2 and Msx3
      clades. The sister-group relationship between MSX1 and MSX2 reflects their
      derivation from the 4p/5q chromosomal paralogon, a derivative of the original
      "MetaHox" cluster. We demonstrate physical linkage between Msx and other MetaHox
      genes (Hmx, NK1, Emx) in a cnidarian. Seven conserved domains, including two
      Groucho repression domains (N- and C-terminal), were present in the ancestral
      Msx. In cnidarians, the Groucho domains are highly similar. In vertebrate Msx1,
      the N-terminal Groucho domain is conserved, while the C-terminal domain diverged
      substantially, implying a novel function. In vertebrate Msx2 and Msx3, the C
      terminal domain was lost. MSX1 mutations associated with ectodermal dysplasia or
      orofacial clefting disorders map to conserved domains in a non-random fashion.
      CONCLUSION: Msx originated from a MetaHox ancestor that also gave rise to Tlx,
      Demox, NK, and possibly EHGbox, Hox and ParaHox genes. Duplication, divergence or
      loss of domains played a central role in the functional evolution of Msx.
      Duplicated domains allow pleiotropically expressed proteins to evolve new
      functions without disrupting existing interaction networks. Human missense
      sequence variants reside within evolutionarily conserved domains, likely
      disrupting protein function. This phylogenomic evaluation of candidate disease
      markers will inform clinical and functional studies.

PMID- 19154606
TI  - Alcohol-induced decrease in muscle protein synthesis associated with increased
      binding of mTOR and raptor: Comparable effects in young and mature rats.
AB  - BACKGROUND: Acute alcohol (EtOH) intoxication decreases muscle protein synthesis
      via inhibition of mTOR-dependent translation initiation. However, these studies
      have been performed in relatively young rapidly growing rats in which muscle
      protein accretion is more sensitive to growth factor and nutrient stimulation.
      Furthermore, some in vivo-produced effects of EtOH vary in an age-dependent
      manner. The hypothesis tested in the present study was that young rats will show
      a more pronounced decrement in muscle protein synthesis than older mature rats in
      response to acute EtOH intoxication. METHODS: Male F344 rats were studied at
      approximately 3 (young) or 12 (mature) months of age. Young rats were injected
      intraperitoneally with 75 mmol/kg of EtOH, and mature rats injected with either
      75 or 90 mmol/kg EtOH. Time-matched saline-injected control rats were included
      for both age groups. Gastrocnemius protein synthesis and the activity of the mTOR
      pathway were assessed 2.5 h after EtOH using [3H]-labeled phenylalanine and the
      phosphorylation of various protein factors known to regulate peptide-chain
      initiation. RESULTS: Blood alcohol levels (BALs) were lower in mature rats
      compared to young rats after administration of 75 mmol/kg EtOH (154 +/- 23 vs 265
      +/- 24 mg/dL). However, injection of 90 mmol/kg EtOH in mature rats produced BALs
      comparable to that of young rats (281 +/- 33 mg/dL). EtOH decreased muscle
      protein synthesis similarly in both young and high-dose EtOH-treated mature rats.
      The EtOH-induced changes in both groups were associated with a concomitant
      reduction in 4E-BP1 phosphorylation, and redistribution of eIF4E between the
      active eIF4E.eIF4G and inactive eIF4E.4EBP1 complex. Moreover, EtOH increased the
      binding of mTOR with raptor in a manner which appeared to be AMPK- and TSC
      independent. In contrast, although muscle protein synthesis was unchanged in
      mature rats given low-dose EtOH, compared to control values, the phosphorylation
      of rpS6 and eIF4G was decreased. CONCLUSION: These data indicate that muscle
      protein synthesis is equally sensitive to the inhibitory effects of EtOH in young
      rapidly growing rats and older mature rats which are growing more slowly, but
      that mature rats must be given a relatively larger dose of EtOH to achieve the
      same BAL. Based on the differential response in mature rats to low- and high-dose
      EtOH, the decreased protein synthesis was associated with a reduction in mTOR
      activity which was selectively mediated via a reduction in 4E-BP1 phosphorylation
      and an increase in mTOR.raptor formation.

PMID- 19154608
TI  - Restorative effect of endurance exercise on behavioral deficits in the chronic
      mouse model of Parkinson's disease with severe neurodegeneration.
AB  - BACKGROUND: Animal models of Parkinson's disease have been widely used for
      investigating the mechanisms of neurodegenerative process and for discovering
      alternative strategies for treating the disease. Following 10 injections with 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 25 mg/kg) and probenecid (250
      mg/kg) over 5 weeks in mice, we have established and characterized a chronic
      mouse model of Parkinson's disease (MPD), which displays severe long-term
      neurological and pathological defects resembling that of the human Parkinson's
      disease in the advanced stage. The behavioral manifestations in this chronic
      mouse model of Parkinson's syndrome remain uninvestigated. The health benefit of
      exercise in aging and in neurodegenerative disorders including the Parkinson's
      disease has been implicated; however, clinical and laboratory studies in this
      area are limited. In this research with the chronic MPD, we first conducted a
      series of behavioral tests and then investigated the impact of endurance exercise
      on the identified Parkinsonian behavioral deficits. RESULTS: We report here that
      the severe chronic MPD mice showed significant deficits in their gait pattern
      consistency and in learning the cued version of the Morris water maze. Their
      performances on the challenging beam and walking grid were considerably
      attenuated suggesting the lack of balance and motor coordination. Furthermore,
      their spontaneous and amphetamine-stimulated locomotor activities in the open
      field were significantly suppressed. The behavioral deficits in the chronic MPD
      lasted for at least 8 weeks after MPTP/probenecid treatment. When the chronic MPD
      mice were exercise-trained on a motorized treadmill 1 week before, 5 weeks
      during, and 8-12 weeks after MPTP/probenecid treatment, the behavioral deficits
      in gait pattern, spontaneous ambulatory movement, and balance performance were
      reversed; whereas neuronal loss and impairment in cognitive skill, motor
      coordination, and amphetamine-stimulated locomotor activity were not altered when
      compared to the sedentary chronic MPD animals. CONCLUSION: This study indicates
      that in spite of the drastic loss of dopaminergic neurons and depletion of
      dopamine in the severe chronic MPD, endurance exercise training effectively
      reverses the Parkinson's like behavioral deficits related to regular movement,
      balance and gait performance.

PMID- 19154609
TI  - Bias in trials comparing paired continuous tests can cause researchers to choose
      the wrong screening modality.
AB  - BACKGROUND: To compare the diagnostic accuracy of two continuous screening tests,
      a common approach is to test the difference between the areas under the receiver
      operating characteristic (ROC) curves. After study participants are screened with
      both screening tests, the disease status is determined as accurately as possible,
      either by an invasive, sensitive and specific secondary test, or by a less
      invasive, but less sensitive approach. For most participants, disease status is
      approximated through the less sensitive approach. The invasive test must be
      limited to the fraction of the participants whose results on either or both
      screening tests exceed a threshold of suspicion, or who develop signs and
      symptoms of the disease after the initial screening tests. The limitations of
      this study design lead to a bias in the ROC curves we call paired screening trial
      bias. This bias reflects the synergistic effects of inappropriate reference
      standard bias, differential verification bias, and partial verification bias. The
      absence of a gold reference standard leads to inappropriate reference standard
      bias. When different reference standards are used to ascertain disease status, it
      creates differential verification bias. When only suspicious screening test
      scores trigger a sensitive and specific secondary test, the result is a form of
      partial verification bias. METHODS: For paired screening tests with bivariate
      normally distributed scores, we give formulae and programs to quantify the effect
      of paired screening trial bias on a paired comparison of area under the curves.
      We fix the prevalence of disease, and the chance a diseased subject manifests
      signs and symptoms. We derive the formulas for true sensitivity and specificity,
      and those for the sensitivity and specificity observed by the study investigator.
      RESULTS: The observed area under the ROC curves is quite different from the true
      area under the ROC curves. The typical direction of the bias is a strong
      inflation in sensitivity, paired with a concomitant slight deflation of
      specificity. CONCLUSION: In paired trials of screening tests, when area under the
      ROC curve is used as the metric, bias may lead researchers to make the wrong
      decision as to which screening test is better.

PMID- 19154610
TI  - Impact of steroid hormone signals on Drosophila cell cycle during development.
AB  - Metamorphosis of Drosophila involves proliferation, differentiation and death of
      larval tissues in order to form the adult fly. The major steroid hormone
      implicated in the larval-pupal transition and adult tissue modelling is ecdysone.
      Previous reviews have draw together studies connecting ecdysone signaling to the
      processes of apoptosis and differentiation. Here we discuss those reports
      connecting the ecdysone pulse to developmentally regulated cell cycle
      progression.

PMID- 19154612
TI  - Mining social mixing patterns for infectious disease models based on a two-day
      population survey in Belgium.
AB  - BACKGROUND: Until recently, mathematical models of person to person infectious
      diseases transmission had to make assumptions on transmissions enabled by
      personal contacts by estimating the so-called WAIFW-matrix. In order to better
      inform such estimates, a population based contact survey has been carried out in
      Belgium over the period March-May 2006. In contrast to other European surveys
      conducted simultaneously, each respondent recorded contacts over two days.
      Special attention was given to holiday periods, and respondents with large
      numbers of professional contacts. METHODS: Participants kept a paper diary with
      information on their contacts over two different days. A contact was defined as a
      two-way conversation of at least three words in each others proximity. The
      contact information included the age of the contact, gender, location, duration,
      frequency, and whether or not touching was involved. For data analysis, we used
      association rules and classification trees. Weighted generalized estimating
      equations were used to analyze contact frequency while accounting for the
      correlation between contacts reported on the two different days. A contact
      surface, expressing the average number of contacts between persons of different
      ages was obtained by a bivariate smoothing approach and the relation to the so
      called next-generation matrix was established. RESULTS: People mostly mixed with
      people of similar age, or with their offspring, their parents and their
      grandparents. By imputing professional contacts, the average number of daily
      contacts increased from 11.84 to 15.70. The number of reported contacts depended
      heavily on the household size, class size for children and number of professional
      contacts for adults. Adults living with children had on average 2 daily contacts
      more than adults living without children. In the holiday period, the daily
      contact frequency for children and adolescents decreased with about 19% while a
      similar observation is made for adults in the weekend. These findings can be used
      to estimate the impact of school closure. CONCLUSION: We conducted a diary based
      contact survey in Belgium to gain insights in social interactions relevant to the
      spread of infectious diseases. The resulting contact patterns are useful to
      improve estimating crucial parameters for infectious disease transmission models.

PMID- 19154611
TI  - Characterization of gene expression profiles for different types of mast cells
      pooled from mouse stomach subregions by an RNA amplification method.
AB  - BACKGROUND: Mast cells (MCs) play pivotal roles in allergy and innate immunity
      and consist of heterogenous subclasses. However, the molecular basis determining
      the different characteristics of these multiple MC subclasses remains unclear.
      RESULTS: To approach this, we developed a method of RNA extraction/amplification
      for intact in vivo MCs pooled from frozen tissue sections, which enabled us to
      obtain the global gene expression pattern of pooled MCs belonging to the same
      subclass. MCs were isolated from the submucosa (sMCs) and mucosa (mMCs) of mouse
      stomach sections, respectively, 15 cells were pooled, and their RNA was
      extracted, amplified and subjected to microarray analysis. Known marker genes
      specific for mMCs and sMCs showed expected expression trends, indicating accuracy
      of the analysis. We identified 1,272 genes showing significantly different
      expression levels between sMCs and mMCs, and classified them into clusters on the
      basis of similarity of their expression profiles compared with bone marrow
      derived MCs, which are the cultured MCs with so-called 'immature' properties.
      Among them, we found that several key genes such as Notch4 had sMC-biased
      expression and Ptgr1 had mMC-biased expression. Furthermore, there is a
      difference in the expression of several genes including extracellular matrix
      protein components, adhesion molecules, and cytoskeletal proteins between the two
      MC subclasses, which may reflect functional adaptation of each MC to the mucosal
      or submucosal environment in the stomach. CONCLUSION: By using the method of RNA
      amplification from pooled intact MCs, we characterized the distinct gene
      expression profiles of sMCs and mMCs in the mouse stomach. Our findings offer
      insight into possible unidentified properties specific for each MC subclass.

PMID- 19154613
TI  - Isotretinoin and psychopathology: a review.
AB  - Isotretinoin, a synthetic oral retinoid that is used against severe nodulocystic
      acne, has been associated with various psychiatric side effects such as
      depression, suicidality and psychotic symptoms. A great number of reports on its
      effects have been published since its introduction into the market. However, a
      causal relationship has not been established and the link between isotretinoin
      use and psychiatric events remains controversial. The present paper reviews the
      available evidence regarding the association of isotretinoin and psychiatric side
      effects. All published material reporting psychiatric side effects following
      isotretinoin treatment, including case reports, case series, reports from adverse
      drug event reporting systems, prospective surveys and retrospective case-control
      studies, are presented. In addition, the neurobiology of the retinoids and
      possible biological mechanisms that may lead to psychopathology are described.

PMID- 19154615
TI  - Neural network committees for finger joint angle estimation from surface EMG
      signals.
AB  - BACKGROUND: In virtual reality (VR) systems, the user's finger and hand positions
      are sensed and used to control the virtual environments. Direct biocontrol of VR
      environments using surface electromyography (SEMG) signals may be more
      synergistic and unconstraining to the user. The purpose of the present
      investigation was to develop a technique to predict the finger joint angle from
      the surface EMG measurements of the extensor muscle using neural network models.
      METHODOLOGY: SEMG together with the actual joint angle measurements were obtained
      while the subject was performing flexion-extension rotation of the index finger
      at three speeds. Several neural networks were trained to predict the joint angle
      from the parameters extracted from the SEMG signals. The best networks were
      selected to form six committees. The neural network committees were evaluated
      using data from new subjects. RESULTS: There was hysteresis in the measured SMEG
      signals during the flexion-extension cycle. However, neural network committees
      were able to predict the joint angle with reasonable accuracy. RMS errors ranged
      from 0.085 +/- 0.036 for fast speed finger-extension to 0.147 +/- 0.026 for slow
      speed finger extension, and from 0.098 +/- 0.023 for the fast speed finger
      flexion to 0.163 +/- 0.054 for slow speed finger flexion. CONCLUSION: Although
      hysteresis was observed in the measured SEMG signals, the committees of neural
      networks were able to predict the finger joint angle from SEMG signals.

PMID- 19154614
TI  - Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3
      dioxygenase activation in a male cohort.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a common disorder that affects 10
      15% of the population. Although characterised by a lack of reliable biological
      markers, the disease state is increasingly viewed as a disorder of the brain-gut
      axis. In particular, accumulating evidence points to the involvement of both the
      central and peripheral serotonergic systems in disease symptomatology.
      Furthermore, altered tryptophan metabolism and indoleamine 2,3-dioxygenase (IDO)
      activity are hallmarks of many stress-related disorders. The kynurenine pathway
      of tryptophan degradation may serve to link these findings to the low level
      immune activation recently described in IBS. In this study, we investigated
      tryptophan degradation in a male IBS cohort (n = 10) and control subjects (n =
      26). METHODS: Plasma samples were obtained from patients and healthy controls.
      Tryptophan and its metabolites were measured by high performance liquid
      chromatography (HPLC) and neopterin, a sensitive marker of immune activation, was
      measured using a commercially available ELISA assay. RESULTS: Both kynurenine
      levels and the kynurenine:tryptophan ratio were significantly increased in the
      IBS cohort compared with healthy controls. Neopterin was also increased in the
      IBS subjects and the concentration of the neuroprotective metabolite kynurenic
      acid was decreased, as was the kynurenic acid:kynurenine ratio. CONCLUSION: These
      findings suggest that the activity of IDO, the immunoresponsive enzyme which is
      responsible for the degradation of tryptophan along this pathway, is enhanced in
      IBS patients relative to controls. This study provides novel evidence for an
      immune-mediated degradation of tryptophan in a male IBS population and identifies
      the kynurenine pathway as a potential source of biomarkers in this debilitating
      condition.

PMID- 19154616
TI  - Prognostic value of metastin expression in human pancreatic cancer.
AB  - BACKGROUND: KiSS-1 was identified as a metastasis-suppressing gene in melanoma
      cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the
      ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in
      tumor progression is not fully understood. METHODS: We investigated the clinical
      significance of metastin and GPR54 expression in pancreatic cancer. We evaluated
      immunohistochemical expression of metastin and GPR54 in pancreatic ductal
      adenocarcinoma tissues obtained from 53 consecutive patients who underwent
      resection between July 2003 and May 2007 at Kyoto University Hospital. In 23
      consecutive patients, the plasma metastin level was measured before surgery by
      enzyme immunoassay. RESULTS: Strong immunohistochemical expression of metastin
      was detected in 13 tumors (24.5%), while strong expression of GPR54 was detected
      in 30 tumors (56.6%). Tumors that were negative for both metastin and GPR54
      expression were significantly larger than tumors that were positive for either
      metastin or GPR54 (p = 0.047). Recurrence was less frequent in patients who had
      metastin-positive tumors compared with those who had metastin-negative tumors
      (38.5% versus 70.0%, p = 0.04). Strong expression of metastin and GPR54 was
      significantly correlated with longer survival (p = 0.02). Metastin expression by
      pancreatic cancer was an independent prognostic factor for longer survival
      (hazard ratio, 2.1; 95% confidence interval, 1.1-4.7; p = 0.03), and the patients
      with a high plasma metastin level (n = 6) did not die after surgical resection.
      CONCLUSION: Strong expression of metastin and GPR54 by pancreatic cancer is
      associated with longer survival. Metastin expression is an independent prognostic
      factor for the survival of pancreatic cancer patients. The plasma metastin level
      could become a noninvasive prognostic factor for the assessment of pancreatic
      cancer.

PMID- 19154617
TI  - Metabolic syndrome and physical activity in southern Brazilian community-dwelling
      elders: a population-based, cross-sectional study.
AB  - BACKGROUND: The association between a sedentary lifestyle and obesity is well
      documented, and is linked to an increased prevalence of metabolic syndrome (MS).
      There is some evidence that information regarding the health benefits of physical
      activity is beginning to impact on the elderly people and is beginning to change
      their behavior. We aimed to investigate the level of physical activity undertaken
      by elderly people with MS and those without this condition. METHODS: We evaluated
      362 community-dwelling elders of Novo Hamburgo, southern Brazil. Diagnosis of MS
      was based on the International Diabetes Federation criteria and the physical
      activity (PA) level was estimated by the International Physical Activity
      Questionnaire. Analysis of covariance was carried out to verify associations
      between MS risk factors and the level of PA. Logistic regression was used to
      estimate the MS odds ratio for each level of PA. RESULTS: No significant
      association was found between MS and the level of physical activity, irrespective
      of sex. The odds ratio for the presence of MS adjusted for sex and age and using
      insufficiently active elderly people as reference was 1.04 (95% CI, 0.6 to 1.7)
      in sufficiently active elderly people and 1.15 (95% CI, 0.7 to 2.0) in very
      active elderly people. CONCLUSION: The elderly citizens of a southern Brazilian
      community who were diagnosed with MS presented the same levels of PA as the
      individuals who did not have this diagnosis. This may imply that information on
      the importance of physical activity has already reached this higher risk
      population.

PMID- 19154618
TI  - Evidence for separate translocation pathways in determining cadmium accumulation
      in grain and aerial plant parts in rice.
AB  - BACKGROUND: Cadmium (Cd) translocation and accumulation in the grain and aerial
      plant parts of rice (Oryza sativa L.) is an important aspect of food safety and
      phytoextraction in areas with contaminated soil. Because control of Cd
      translocation and accumulation is likely to be determined by the plants genetics,
      the Cd contents of grain and the aerial parts of rice may be manipulated to
      improve food safety and for phytoextraction ability. This study studied Cd
      translocation and accumulation and their genetic control in aerial parts of rice
      to provide a starting point for improving food safety and phytoextraction in Cd
      contaminated soils. RESULTS: In the japonica rice cultivar "Nipponbare", Cd
      accumulated in leaves and culms until heading, and in culms and ears after
      heading. Two quantitative trait loci (QTLs) from indica cv. "Kasalath", qcd4-1
      and qcd4-2, affect Cd concentrations in upper plant parts just before heading.
      Three near-isogenic lines (NILs) with qcd4-1 and qcd4-2 were selected from the
      "Nipponbare" background, and were analyzed for the effects of each QTL, and for
      interactions between the two QTLs. From the results compared between "Nipponbare"
      and each NIL, neither QTL influenced total Cd accumulation in aerial parts at 5
      days after heading, but the interaction between two QTLs increased Cd
      accumulation. At 35 days after heading, qcd4-2 had increased Cd accumulation in
      the aerial plant parts and decreased translocation from leaves other than flag
      leaf, but interaction between the two QTLs increased translocation from leaves.
      NILqcd4-1,2 accumulated higher concentrations of Cd in brown rice than
      "Nipponbare". CONCLUSION: Three types of Cd translocation and accumulation
      patterns demonstrated by NILs suggested that the accumulation of Cd in leaves and
      culms before heading, and translocation from them after heading are responsible
      for Cd accumulation in grain. Cd translocation from roots to culms and ears after
      heading may direct Cd to the aerial organs without influencing brown rice
      accumulation.

PMID- 19154619
TI  - Preventing long term relapsing tinea unguium with topical anti-fungal cream: a
      case report.
AB  - BACKGROUND: The patient was aged 34 when he consulted a dermatologist in
      Vancouver BC with onychomycosis affecting the right great toenail. CASE
      PRESENTATION: Trichophyton rubrum was cultured from nail clippings. Griseofulvin
      was taken for 6 months, resulting in clinical and mycological cure. Over the next
      27 years there were multiple relapses. Each course of treatment with oral
      terbinafine (for up to 18 months) or itraconazole resulted in clinical and
      mycological cure. A dermatological colleague suggested the reason for relapse was
      likely to be self re-infection. CONCLUSION: No clinical relapse has occurred with
      once-weekly miconazole cream applied to the toenail and webspaces of the right
      foot over the last four years.

PMID- 19154620
TI  - A Drosophila systems model of pentylenetetrazole induced locomotor plasticity
      responsive to antiepileptic drugs.
AB  - BACKGROUND: Rodent kindling induced by PTZ is a widely used model of
      epileptogenesis and AED testing. Overlapping pathophysiological mechanisms may
      underlie epileptogenesis and other neuropsychiatric conditions. Besides epilepsy,
      AEDs are widely used in treating various neuropsychiatric disorders. Mechanisms
      of AEDs' long term action in these disorders are poorly understood. We describe
      here a Drosophila systems model of PTZ induced locomotor plasticity that is
      responsive to AEDs. RESULTS: We empirically determined a regime in which seven
      days of PTZ treatment and seven days of subsequent PTZ discontinuation
      respectively cause a decrease and an increase in climbing speed of Drosophila
      adults. Concomitant treatment with NaVP and LEV, not ETH, GBP and VGB, suppressed
      the development of locomotor deficit at the end of chronic PTZ phase. Concomitant
      LEV also ameliorated locomotor alteration that develops after PTZ withdrawal.
      Time series of microarray expression profiles of heads of flies treated with PTZ
      for 12 hrs (beginning phase), two days (latent phase) and seven days
      (behaviorally expressive phase) showed only down-, not up-, regulation of genes;
      expression of 23, 2439 and 265 genes were downregulated, in that order. GO
      biological process enrichment analysis showed downregulation of transcription,
      neuron morphogenesis during differentiation, synaptic transmission, regulation of
      neurotransmitter levels, neurogenesis, axonogenesis, protein modification, axon
      guidance, actin filament organization etc. in the latent phase and of glutamate
      metabolism, cell communication etc. in the expressive phase. Proteomic
      interactome based analysis provided further directionality to these events.
      Pathway overrepresentation analysis showed enrichment of Wnt signaling and other
      associated pathways in genes downregulated by PTZ. Mining of available
      transcriptomic and proteomic data pertaining to established rodent models of
      epilepsy and human epileptic patients showed overrepresentation of epilepsy
      associated genes in our PTZ regulated set. CONCLUSION: Systems biology ultimately
      aims at delineating and comprehending the functioning of complex biological
      systems in such details that predictive models of human diseases could be
      developed. Due to immense complexity of higher organisms, systems biology
      approaches are however currently focused on simpler organisms. Amenable to
      modeling, our model offers a unique opportunity to further dissect
      epileptogenesis-like plasticity and to unravel mechanisms of long-term action of
      AEDs relevant in neuropsychiatric disorders.

PMID- 19154621
TI  - Active management of the third stage of labour without controlled cord traction:
      a randomized non-inferiority controlled trial.
AB  - BACKGROUND: The third stage of labour refers to the period between birth of the
      baby and complete expulsion of the placenta. Some degree of blood loss occurs
      after the birth of the baby due to separation of the placenta. This period is a
      risky period because uterus may not contract well after birth and heavy blood
      loss can endanger the life of the mother. Active management of the third stage of
      labour (AMTSL) reduces the occurrence of severe postpartum haemorrhage by
      approximately 60-70%. Active management consists of several interventions
      packaged together and the relative contribution of each of the components is
      unknown. Controlled cord traction is one of those components that require
      training in manual skill for it to be performed appropriately. If it is possible
      to dispense with controlled cord traction without losing efficacy it would have
      major implications for effective management of the third stage of labour at
      peripheral levels of health care. OBJECTIVE: The primary objective is to
      determine whether the simplified package of oxytocin 10 IU IM/IV is not less
      effective than the full AMTSL package. METHODS: A hospital-based, multicentre,
      individually randomized controlled trial is proposed. The hypothesis tested will
      be a non-inferiority hypothesis. The aim will be to determine whether the
      simplified package without CCT, with the advantage of not requiring training to
      acquire the manual skill to perform this task, is not less effective than the
      full AMTSL package with regard to reducing blood loss in the third stage of
      labour.The simplified package will include uterotonic (oxytocin 10 IU IM)
      injection after delivery of the baby and cord clamping and cutting at
      approximately 3 minutes after birth. The full package will include the uterotonic
      injection (oxytocin 10 IU IM), controlled cord traction following observation of
      uterine contraction and cord clamping and cutting at approximately 3 minutes
      after birth. The primary outcome measure is blood loss of 1000 ml or more at one
      hour and up to two hours for women who continue to bleed after one hour. The
      secondary outcomes are blood transfusion, the use of additional uterotonics and
      measure of severe morbidity and maternal death.We aim to recruit 25,000 women
      delivering vaginally in health facilities in eight countries within a 12 month
      recruitment period. MANAGEMENT: Overall trial management will be from HRP/RHR in
      Geneva. There will be eight centres located in Argentina, Egypt, India, Kenya,
      Philippines, South Africa, Thailand and Uganda. There will be an online data
      entry system managed from HRP/RHR. The trial protocol was developed following a
      technical consultation with international organizations and leading researchers
      in the field. EXPECTED OUTCOMES: The main objective of this trial is to
      investigate whether a simplified package of third stage management can be
      recommended without increasing the risk of PPH. By avoiding the need for a manual
      procedure that requires training, the third stage management can be implemented
      in a more widespread and cost-effective way around the world even at the most
      peripheral levels of the health care system. This trial forms part of the
      programme of work to reduce maternal deaths due to postpartum haemorrhage within
      the RHR department in collaboration with other research groups and organizations
      active in the field. TRIAL REGISTRATION: ACTRN12608000434392.

PMID- 19154622
TI  - Effect of a school-based intervention to promote healthy lifestyles in 7-11 year
      old children.
AB  - BACKGROUND: Physical inactivity is recognised as a public health concern within
      children and interventions to increase physical activity are needed. The purpose
      of this research was to evaluate the effect of a school-based healthy lifestyles
      intervention on physical activity, fruit and vegetable consumption, body
      composition, knowledge, and psychological variables. METHOD: A non-randomised
      controlled study involving 8 primary schools (4 intervention, 4 control).
      Participants were 589 children aged 7-11 years. The intervention lasted 10 months
      and comprised a CD-rom learning and teaching resource for teachers; an
      interactive website for pupils, teachers and parents; two highlight physical
      activity events (1 mile school runs/walks); a local media campaign; and a summer
      activity wall planner and record. Primary outcome measures were objectively
      measured physical activity (pedometers and accelerometers) and fruit and
      vegetable consumption. Secondary outcomes included body mass index, waist
      circumference, estimated percent body fat, knowledge, psychological variables.
      Multi-level modelling was employed for the data analysis. RESULTS: Relative to
      children in control schools, those in intervention schools significantly
      increased their total time in moderate-to-vigorous physical activity (MVPA) (by 9
      minutes/day vs a decrease of 10 minutes/day), their time in MVPA bouts lasting at
      least one minute (10 minutes/day increase vs no change) and increased daily steps
      (3059 steps per day increase vs 1527 steps per day increase). A similar pattern
      of results was seen in a subset of the least active participants at baseline.
      Older participants in intervention schools showed a significant slowing in the
      rate of increase in estimated percent body fat, BMI, and waist circumference.
      There were no differences between groups in fruit and vegetable intake. Extrinsic
      motivation decreased more in the intervention group. CONCLUSION: The intervention
      produced positive changes in physical activity levels and body composition. It
      appeared to have little or no effect on consumption of fruit and vegetables.
      Schools are a suitable setting for the promotion of healthy lifestyles although
      more work, particularly focussed on dietary change, is needed in a variety of
      schools and social settings.

PMID- 19154623
TI  - Enzymatic corn wet milling: engineering process and cost model.
AB  - BACKGROUND: Enzymatic corn wet milling (E-milling) is a process derived from
      conventional wet milling for the recovery and purification of starch and co
      products using proteases to eliminate the need for sulfites and decrease the
      steeping time. In 2006, the total starch production in USA by conventional wet
      milling equaled 23 billion kilograms, including modified starches and starches
      used for sweeteners and ethanol production 1. Process engineering and cost models
      for an E-milling process have been developed for a processing plant with a
      capacity of 2.54 million kg of corn per day (100,000 bu/day). These models are
      based on the previously published models for a traditional wet milling plant with
      the same capacity. The E-milling process includes grain cleaning, pretreatment,
      enzymatic treatment, germ separation and recovery, fiber separation and recovery,
      gluten separation and recovery and starch separation. Information for the
      development of the conventional models was obtained from a variety of technical
      sources including commercial wet milling companies, industry experts and
      equipment suppliers. Additional information for the present models was obtained
      from our own experience with the development of the E-milling process and trials
      in the laboratory and at the pilot plant scale. The models were developed using
      process and cost simulation software (SuperPro Designer) and include processing
      information such as composition and flow rates of the various process streams,
      descriptions of the various unit operations and detailed breakdowns of the
      operating and capital cost of the facility. RESULTS: Based on the information
      from the model, we can estimate the cost of production per kilogram of starch
      using the input prices for corn, enzyme and other wet milling co-products. The
      work presented here describes the E-milling process and compares the process, the
      operation and costs with the conventional process. CONCLUSION: The E-milling
      process was found to be cost competitive with the conventional process during
      periods of high corn feedstock costs since the enzymatic process enhances the
      yields of the products in a corn wet milling process. This model is available
      upon request from the authors for educational, research and non-commercial uses.

PMID- 19154624
TI  - Onchocerciasis Control: Vision for the Future from a Ghanian perspective.
AB  - Since 1987 onchocerciasis control has relied on the donation of ivermectin
      (Mectizan(R), Merck & Co., Inc.) through the Mectizan Donation Programme.
      Recently, concern has been raised over the appearance of suboptimal responses to
      ivermectin in Ghana - highlighting the potential threat of the development of
      resistance to ivermectin. This report summarises a meeting held in Ghana to set
      the research agenda for future onchocerciasis control. The aim of this workshop
      was to define the research priorities for alternative drug and treatment regimes
      and control strategies to treat populations with existing evidence of suboptimal
      responsiveness and define research priorities for future control strategies in
      the event of the development of widespread ivermectin resistance.

PMID- 19154626
TI  - Prolonged use of dexmedetomidine in the paediatric cardiothoracic intensive care
      unit.
AB  - BACKGROUND: Dexmedetomidine is an alpha2-adrenergic agonist that causes sleep
      like sedation and mild analgesia without narcosis or respiratory depression, and
      has relative cardiovascular stability. Due to these properties, it may be an
      effective agent for prolonged use in the sedation of patients in the paediatric
      cardiothoracic intensive care unit. We reviewed our experience with the drug to
      detail its safety and efficacy. METHODS: We conducted a retrospective chart
      review of all patients who received dexmedetomidine over a six month period in a
      dedicated paediatric cardiothoracic intensive care unit. Patients were identified
      from pharmacy records showing administration of drugs. We collected demographic
      data, information relating to doses of dexmedetomidine, physiologic parameters,
      and clinical outcomes. RESULTS: We identified 54 patients who received the drug.
      The median age of recipients was 6 months, with a range from 1 day to 16 years.
      The mean duration of administration was 37.3 hours, with a range from 2 to 177
      hours. The mean duration of continuation of administration after extubation was
      16.7 hours, with a range from zero to 112.5 hours. Physiologically, there were no
      clinically significant changes in mean arterial pressure, heart rate, respiratory
      rate, or saturations of oxygen before, during, or after utilization of the drug.
      Use of dexmedetomidine significantly reduced the need to administer narcotics,
      and scores using the COMFORT system were not different between patients who
      received dexmedetomidine and those who did not. CONCLUSIONS: In this limited and
      retrospective review, dexmedetomidine was found to be safe and efficacious. Its
      use as a sedative agent for extended periods of time in critically-ill children
      deserves investigation in a prospective and controlled manner.

PMID- 19154625
TI  - Reliability of clinical tests to evaluate nerve function and mechanosensitivity
      of the upper limb peripheral nervous system.
AB  - BACKGROUND: Clinical tests to assess peripheral nerve disorders can be classified
      into two categories: tests for afferent/efferent nerve function such as nerve
      conduction (bedside neurological examination) and tests for increased
      mechanosensitivity (e.g. upper limb neurodynamic tests (ULNTs) and nerve
      palpation). Reliability reports of nerve palpation and the interpretation of
      neurodynamic tests are scarce. This study therefore investigated the intertester
      reliability of nerve palpation and ULNTs. ULNTs were interpreted based on symptom
      reproduction and structural differentiation. To put the reliability of these
      tests in perspective, a comparison with the reliability of clinical tests for
      nerve function was made. METHODS: Two experienced clinicians examined 31 patients
      with unilateral arm and/or neck pain. The examination included clinical tests for
      nerve function (sensory testing, reflexes and manual muscle testing (MMT)) and
      mechanosensitivity (ULNTs and palpation of the median, radial and ulnar nerve).
      Kappa statistics were calculated to evaluate intertester reliability. A meta
      analysis determined an overall kappa for the domains with multiple kappa values
      (MMT, ULNT, palpation). We then compared the difference in reliability between
      the tests of mechanosensitivity and nerve function using a one-sample t-test.
      RESULTS: We observed moderate to substantial reliability for the tests for
      afferent/efferent nerve function (sensory testing: kappa = 0.53; MMT: kappa =
      0.68; no kappa was calculated for reflexes due to a lack of variation). Tests to
      investigate mechanosensitivity demonstrated moderate reliability (ULNT: kappa =
      0.45; palpation: kappa = 0.59). When compared statistically, there was no
      difference in reliability for tests for nerve function and mechanosensitivity (p
      = 0.06). CONCLUSION: This study demonstrates that clinical tests which evaluate
      increased nerve mechanosensitivity and afferent/efferent nerve function have
      comparable moderate to substantial reliability. To further investigate the
      clinometric properties of these tests, more studies are needed to evaluate their
      validity.

PMID- 19154627
TI  - The monitoring of venous saturations of oxygen in children with congenitally
      malformed hearts.
AB  - Mixed venous saturation of oxygen has for some time been used as a tool to assess
      the adequacy of systemic delivery of oxygen in intensive care. In the post
      operative child with cardiac disease, it is increasingly being used to assess
      adequacy of cardiac output. In many of these patients, true sampling of mixed
      venous saturation of oxygen is not possible due to the infrequent use of
      pulmonary arterial catheters, or the presence of intra-cardiac left to right
      shunting leading to mixing of systemic and pulmonary venous blood. The use of
      saturation of oxygen in the central venous blood as a surrogate for mixed venous
      saturation of oxygen has been widely investigated in adults, but its use remains
      controversial. In this review, we discuss the theory behind the use of mixed
      venous saturation of oxygen in evaluating cardiac output, the problems pertinent
      to those patients with congenitally malformed hearts, and explore the evidence
      for central venous saturation of oxygen as a surrogate for mixed venous
      saturation of oxygen, and its use as a therapeutic target to improve outcomes in
      this population of patients.

PMID- 19154628
TI  - The logic for extending the use of echocardiography beyond childhood to detect
      subclinical rheumatic heart disease.
AB  - Rheumatic heart disease is the only residual morbidity, and the sole cause of
      mortality, from rheumatic fever. Echocardiography is ideally suited to confirm
      and follow the course of rheumatic heart disease. Additionally, both minimal
      valvar pathology in children, and extensive valvar pathology in adults, may not
      cause a murmur and can be detected only by echocardiography. Whenever possible,
      echocardiography should be routinely employed for management of patients with
      rheumatic fever or suspected rheumatic fever.

PMID- 19154629
TI  - Nicotine- and methamphetamine-induced dopamine release evaluated with in-vivo
      binding of radiolabelled raclopride to dopamine D2 receptors: comparison with in
      vivo microdialysis data.
AB  - The effect of substances which alter extracellular dopamine (DA) concentration
      has been studied by measuring changes in the binding of radiolabelled raclopride,
      a DA D2 receptor ligand that is sensitive to endogenous DA. To better
      characterize the relationship between extracellular DA concentration and DA D2
      receptor binding of raclopride, we compared the changes of extracellular DA
      concentration (measured using in-vivo microdialysis) and in-vivo [3H]raclopride
      binding induced by different doses of methamphetamine (Meth) and nicotine, drugs
      that enhance DA release with and without blocking DA transporters (DATs),
      respectively, in rat striatum. Nicotine elicited a modest increase of striatal
      extrasynaptic extracellular DA, while Meth produced a marked increase of striatal
      extrasynaptic DA in a dose-dependent manner. There was a close correlation
      between the decrease in [3H]raclopride in-vivo binding and the increase in
      extrasynaptic DA concentration induced by both nicotine (r2=0.95, p<0.001) and
      Meth (r2=0.98, p=0.001), supporting the usefulness of the radiolabelled
      raclopride-binding measurement for the non-invasive assessment of DA release
      following interventions in the living brain. However, the linear regression
      analysis revealed that the ratio of percent DA increase to percent [3H]raclopride
      binding reduction was 25-fold higher for Meth (34.8:1) than for nicotine (1.4:1).
      The apparent discrepancy in the extrasynaptic DA-[3H]raclopride binding
      relationship between the DA-enhancing drugs with and without DAT-blocking
      property indicates that the competition between endogenous DA and radiolabelled
      raclopride takes place at the intrasynaptic rather than extrasynaptic DA D2
      receptors and reflects synaptic concentration of DA.

PMID- 19154630
TI  - The effect of a full agonist/antagonist of the D1 receptor on locomotor activity,
      sensorimotor gating and cognitive function in dizocilpine-treated rats.
AB  - Cognitive impairment has been found across all subtypes of schizophrenia. The
      location and function of dopamine-1 receptors (D1Rs) make them attractive targets
      for the treatment of cognitive impairment in schizophrenia. Here we investigate
      the systemic effect of a D1R agonist (A77636) and antagonist (SCH 23390) on
      hyperlocomotor activity and cognitive deficit induced by an NMDA receptor
      antagonist (MK-801). Wistar rats (250-300 g) received A77636 (0.1, 0.5 or 1
      mg/kg) or SCH 23390 (0.02 or 0.05 mg/kg) with MK-801 (0.1 mg/kg) or saline for 4
      d. On day 4 we assessed the prepulse inhibition of the acoustic startle response,
      locomotor activity in a novel arena and active allothetic place avoidance
      (spatial memory task) 15 min after the last injection. Systematic administration
      of the D1R agonist at 0.1 mg/kg ameliorates cognitive dysfunction in our model of
      schizophrenia, but increases stereotypy and locomotor activity (model of
      psychotic symptoms) at higher doses (0.5 or 1 mg/kg). Administration of the D1R
      antagonist had no effect on cognitive function, but decreased hyperlocomotion
      induced by MK-801. Thus, based on our results, over-activation of D1Rs may
      exacerbate psychotic symptoms in patients with schizophrenia.

PMID- 19154631
TI  - Association of X-box binding protein 1 ( XBP1) genotype with morning cortisol and
      1-year clinical course after a major depressive episode.
AB  - Brain diseases including Alzheimer's and Parkinson's involve the cellular
      'unfolded protein' (UPR) stress response. Psychiatric illnesses such as
      depressive disorders are thought to involve brain stress-response pathways. The
      XBP1 gene encodes a key transcription factor in the UPR stress response and
      therefore could be involved in the pathophysiology of depressive disorders. A
      functional polymorphism (-116C-->G) in the XBP1 promoter was linked in some
      studies to bipolar disorder. Among 132 adults (mean age 39 yr) who presented with
      a major depressive episode, this polymorphism was found to be associated with a
      worse course during 1-yr prospective follow-up. In a subgroup (n=22), the
      polymorphism was associated with higher plasma levels of the stress hormone
      cortisol. The results suggest that hypothalamic-pituitary-adrenocortical and
      cellular stress pathways involving the XBP1 gene may be involved in the
      pathophysiology of major depressive disorder. These relationships merit further
      study.

PMID- 19154632
TI  - Interaction between the 5-HTTLPR serotonin transporter polymorphism and
      environmental adversity for mood and anxiety psychopathology: evidence from a
      high-risk community sample of young adults.
AB  - Previous research examining gene-environment interaction (GxE) with regard to
      vulnerability to depression and anxiety has yielded conflicting results. The
      present study was designed to further investigate GxE between 5-HTTLPR and
      exposure to environmental adversity, using different phenotypic and genotypic
      characterizations as well as different types of adversity within a prospective
      study design. Data were available from an ongoing epidemiological cohort study
      following the outcome of early risk factors from birth to adulthood. At age 19
      yr, 309 participants (142 males, 167 females) were characterized on measures of
      depression and anxiety through interview and questionnaire (DSM-IV diagnosis,
      Beck Depression Inventory, Harm Avoidance). Environmental adversity was assessed
      at birth (family adversity), and at age 19 yr (stressful life events). Bi- and
      tri-allelic 5-HTTLPR genotypes were obtained from genomic DNA. Results indicated
      that depression and anxiety in 19-yr-olds were strongly associated with both
      family adversity and stressful life events. Individuals with the LL genotype of 5
      HTTLPR who were exposed to high family adversity displayed significantly higher
      rates of depressive or anxiety disorders and had more depressive symptoms than
      those without either condition. This GxE replicates recent findings from an
      epidemiological cohort study of adolescents but is in contrast to many previous
      reports suggesting an interaction with the S allele. No evidence for GxE was
      obtained with regard to current stressful life events and trait anxiety. One
      possible source for the conflicting findings might be attributed to heterogeneity
      in depression phenotypes and environmental adversity.

PMID- 19154633
TI  - Are we paying enough attention to adolescent nutrition?

PMID- 19154634
TI  - In this issue. Public health nutrition issues pertinent to adolescence.

PMID- 19154636
TI  - Time to stop giving indiscriminate massive doses of synthetic vitamin A to Indian
      children.

PMID- 19154637
TI  - Out of the box. Nutrition on a budget.

PMID- 19154638
TI  - Public health nutrition. Dietary guidelines. We have traction in Australia.

PMID- 19154639
TI  - Public health nutrition. Dietary guidelines. We have traction in Australia.

PMID- 19154640
TI  - Tom Marchione.

PMID- 19154641
TI  - Leaf concentrate. Undernutrition. AIDS. The elimination of NOMA (Cancrum oris)?

PMID- 19154642
TI  - The influence of clonal diversity and intensity-dependence on trematode
      infections in an amphipod.
AB  - Individual animals are often infected not only by different parasite species, but
      also by multiple genotypes of the same parasite species. Genetic relatedness
      among parasites sharing a host is expected to modulate their strategies of
      resource exploitation, growth and virulence. We experimentally examined the
      effects that genetic diversity and infection intensity had on host mortality,
      infectivity and growth of the marine trematode Maritrema novaezealandensis in
      amphipod hosts. The presence of 2 versus 1 parasite genotype during infection did
      not influence subsequent host mortality, had different effects on infectivity
      among genotypes and did not influence growth or variation in parasite growth.
      Density-dependent growth reductions revealed that the number of parasites
      infecting a host was more important than their genetic relatedness. Temperature,
      host size, and host sex influenced the degree to which density-dependent factors
      affected parasite growth. Our results suggest that the effects of parasite
      relatedness vary among parasite genotypes in this trematode species, and reveal
      that many factors play an important role during parasite development and
      transmission.

PMID- 19154643
TI  - Population dynamics of Antarctophthirus microchir (Anoplura: Echinophthiriidae)
      in pups from South American sea lion, Otaria flavescens, in Northern Patagonia.
AB  - We analysed population dynamics of the louse Antarctophthirus microchir in pups
      of the South American sea lion, Otaria flavescens, at the Punta Leon rookery
      (Argentina) over a period of 2 years. A total of 136 pups were aged and marked at
      the beginning of the lactation period ashore, then sampled for lice at different
      times within 30 days. Sampling was restricted to the chest and belly, two sites
      where lice were especially abundant. This concentration on ventral areas might
      protect lice from thermal stress in the austral summer. Infestation patterns in
      pups 3 days old suggested that the potential for transmission increased from
      first nymphs to adults. Population trends of each instar with pup age, based on
      standardised values of abundance, were conserved between years, reflecting the
      basic dynamics of recruitment and reproduction. However, trends based on log
      transformed abundances varied significantly between years; apparently,
      environmental conditions affected growth of lice populations differently each
      year. Stage-based deterministic models for population growth of A. microchir
      suggested generation times from 18 to 23 days. Accordingly, only 2 lice
      generations might be produced before pups start going to the sea. Shortening the
      cycle to accommodate a third generation might be risky, whereas a 2-generation
      cycle might at least result in larger females producing higher numbers of viable
      offspring.

PMID- 19154644
TI  - Elevated levels of urinary hydrogen peroxide, advanced oxidative protein product
      (AOPP) and malondialdehyde in humans infected with intestinal parasites.
AB  - Oxidative stress has been implicated as an important pathogenic factor in the
      pathophysiology of various life-threatening diseases such as cancer,
      cardiovascular diseases and diabetes. It occurs when the production of free
      radicals (generated during aerobic metabolism, inflammation, and infections)
      overcome the antioxidant defences in the body. Although previous studies have
      implied that oxidative stress is present in serum of patients with parasitic
      infection there have been no studies confirming oxidative stress levels in the
      Malaysian population infected with intestinal parasites. Three biochemical assays
      namely hydrogen peroxide (H2O2), lipid peroxidation (LP) and advanced oxidative
      protein product (AOPP) assays were carried out to measure oxidative stress levels
      in the urine of human subjects whose stools were infected with parasites such as
      Blastocystis hominis, Ascaris, Trichuris, hookworm and microsporidia. The levels
      of H2O2, AOPP and LP were significantly higher (P<0.001, P<0.05 and P<0.05
      respectively) in the parasite-infected subjects (n=75) compared to the controls
      (n=95). In conclusion, the study provides evidence that oxidative stress is
      elevated in humans infected by intestinal parasites. This study may influence
      future researchers to consider free radical-related pathways to be a target in
      the interventions of new drugs against parasitic infection and related diseases.

PMID- 19154645
TI  - Identification and molecular characterization of numerous Histomonas meleagridis
      proteins using a cDNA library.
AB  - SUMMARYHistomonas meleagridis is a protozoan parasite of various galliform birds
      causing a type of enterohepatitis termed histomonosis or 'blackhead disease'. Due
      to the ban of chemotherapeutic substances and an increase in free-range poultry
      production, histomonosis is currently a re-emerging disease. So far limited
      molecular knowledge is available. In the present work, mRNAs coding for antigenic
      proteins of H. meleagridis were identified. For this purpose, a cDNA expression
      library was constructed from a mono-eukaryotic culture of H. meleagridis. The
      library was screened with polyclonal rabbit serum raised against purified H.
      meleagridis trophozoites. Polyclonal rabbit serum specifically recognized the
      same major H. meleagridis antigens as chicken and turkey sera originating from
      animal trials, but displayed a significantly lower bacteria-dependent background
      signal. After 2 rounds of screening, a total of 95 positive clones were
      sequenced. Bioinformatics analyses were performed on nucleotide and deduced amino
      acid sequences, identifying 37 unique clones. Based on the homology to other
      protozoan parasites, mostly Trichomonas vaginalis, the clones were grouped
      according to functional aspects: structural proteins, possible surface proteins,
      oxygen reducing proteins, ribosomal proteins, protein kinases and various other
      intracellular proteins.

PMID- 19154648
TI  - Malignant triton tumour of right paranasal sinuses: case report.
AB  - OBJECTIVE: We report an extremely rare case of malignant triton tumour. METHOD:
      Case report and review of the world literature concerning malignant triton tumour
      and heredity. RESULTS: We present the case of a 47-year-old woman who underwent a
      lateral rhinotomy surgical resection of a malignant triton tumour of the right
      paranasal sinuses, a rare location for this tumour. Thereafter, she received
      adjuvant radiotherapy. The prognosis for this group of tumours is poor. Radical
      surgical excision of the tumour followed by radiation therapy must be the
      treatment of choice. CONCLUSION: To our knowledge, this is a rare report in the
      world literature of malignant triton tumour. This case indicates that malignant
      triton tumour of the paranasal sinuses is a rare disease which otolaryngologists
      should be aware of, and one which should be included in the differential
      diagnosis of malignant lesions involving the sinonasal tract.

PMID- 19154646
TI  - Impaired inhibitory control is associated with higher-order repetitive behaviors
      in autism spectrum disorders.
AB  - BACKGROUND: Impairments in executive cognitive control, including a reduced
      ability to inhibit prepotent responses, have been reported in autism spectrum
      disorders (ASD). These deficits may underlie patterns of repetitive behaviors
      associated with the disorder. METHOD: Eighteen individuals with ASD and 15 age-
      and IQ-matched healthy individuals performed an antisaccade task and a visually
      guided saccade control task, each with gap and overlap conditions. Measures of
      repetitive behaviors were obtained using the Autism Diagnostic Inventory-Revised
      (ADI-R) and examined in relation to neurocognitive task performance. RESULTS:
      Individuals with an ASD showed increased rates of prosaccade errors (failures to
      inhibit prepotent responses) on the antisaccade task regardless of task condition
      (gap/overlap). Prosaccade error rates were associated with the level of higher
      order (e.g. compulsions, preoccupations) but not sensorimotor repetitive
      behaviors in ASD. CONCLUSIONS: Neurocognitive disturbances in voluntary
      behavioral control suggest that alterations in frontostriatal systems contribute
      to higher-order repetitive behaviors in ASD.

PMID- 19154647
TI  - Influence of the fusiform gyrus on amygdala response to emotional faces in the
      non-clinical range of social anxiety.
AB  - BACKGROUND: Social anxiety often involves a combination of hypervigilance and
      avoidance to potentially warning signals including the facial expression of
      emotions. Functional imaging has demonstrated an increase in amygdala response to
      emotional faces in subjects with social anxiety. Nevertheless, it is unclear to
      what extent visual areas processing faces influence amygdala reactivity in
      different socially anxious individuals. We assessed the influence of the fusiform
      gyrus activation on amygdala response to emotional faces in the non-clinical
      range of social anxiety. METHOD: Twenty-two normal subjects showing a wide range
      in social anxiety scores were examined using functional magnetic resonance
      imaging (fMRI) during the processing of happy and fearful faces. A dimensional
      analysis approach was used involving voxel-wise mapping of the correlation
      between subjects' social anxiety scores and amygdala activation, before and after
      controlling for fusiform gyrus activation. RESULTS: We observed that only after
      controlling for subjects' level of activation of the fusiform gyrus was there an
      association between social anxiety ratings and amygdala response to both happy
      and fearful faces. The fusiform gyrus influence was more robust during the fear
      condition. Of note, fusiform gyrus response to fearful faces showed a negative
      correlation with additional behavioral assessments related to avoidance,
      including social anxiety scores, harm avoidance and sensitivity to punishment.
      CONCLUSIONS: Relevant interactions among the emotional face-processing stages
      exist in the non-clinical range of social anxiety that may ultimately attenuate
      amygdala responses. Future research will help to establish the role of this
      effect in a clinical context.

PMID- 19154649
TI  - Melioidosis and tuberculosis: dual pathogens in a neck abscess.
AB  - INTRODUCTION: Melioidosis is an infectious disease caused by a saprophytic
      bacterium, Burkholderia pseudomallei. It is endemic to Southeast Asia and
      Northern Australia. It may manifest as a pulmonary lesion, osteomyelitis,
      abscesses in soft tissue and various organs, or as septicaemia. CASE REPORT: We
      report a case of a 40-year-old, diabetic man who presented with a neck lump
      resulting from super-infection of a tuberculosis cavity with B pseudomallei. The
      patient was successfully managed by drainage along with meticulous excision of
      the capsule and prolonged antibiotic and anti-tubercular treatment. DISCUSSION:
      Melioidosis may be confused diagnostically with tuberculosis, as both diseases
      are endemic in the same regions. Our patient was unfortunate to suffer from both
      endemic diseases simultaneously, perhaps representing the first such case in the
      world literature. CONCLUSION: Increased awareness of melioidosis is important as,
      although the organism is easy to culture, it may be dismissed as a contaminant.

PMID- 19154650
TI  - Aggravation of pathogenesis mediated by ochratoxin A in mice infected with
      Trypanosoma brucei rhodesiense.
AB  - Mice fed 1.5 mg ochratoxin A (OTA) per kg body weight and infected with
      Trypanosoma brucei rhodesiense were compared with trypanosome-infected placebo
      fed and uninfected OTA-fed controls. Uninfected OTA-fed mice showed fever,
      lethargy, facial and eyelid oedemas, mild hepatitis and nephritis, and high
      survival. Infected placebo-fed controls had mean pre-patent period (PPP) of 3.26
      days, lethargy, dyspnoea, fever, facial and scrotal oedema, survival of 33-65
      days, reduced red cell counts (RCC: 10.96-6.87x106 cells/microl of blood), packed
      cell volume (PCV: 43.19-26.36%), haemoglobin levels (Hb: 13.37-7.92 g/dL) and
      mean corpuscular volume (MCV) of 37.96-41.31 fL, hepatosplenomegaly, generalized
      oedemas, heart congestion, hepatitis and nephritis. Compared to infected placebo
      fed controls, infected OTA-fed mice had significantly (P<0.05) shorter mean PPP
      (2.58 days), reduced survival (6-47 days), more pronounced fever and dyspnoea.
      The latter had significantly (P<0.05) reduced RCC (10.74-4.56x106 cells/microl of
      blood), PCV (43.90-20.78%), Hb (13.06-5.74 g/dL), increased MCV (39.10-43.97 fL),
      severe generalized oedemas, haemorrhages, congestion, hepatic haemosiderosis,
      hepatitis, nephritis, endocarditis, pericarditis and exclusively, splenic
      macrophage and giant cell hyperplasia, expanded red pulp and splenic
      erythrophagocytosis. It was concluded that OTA aggravated the pathogenesis of T.
      b. rhodesiense infection in mice, and should therefore be taken into
      consideration during trypanosomosis control programmes.

PMID- 19154651
TI  - Heligmosomoides polygyrus reduces infestation of Ixodes ricinus in free-living
      yellow-necked mice, Apodemus flavicollis.
AB  - Free-living animals are usually inhabited by a community of parasitic species
      that can interact with each other and alter both host susceptibility and parasite
      transmission. In this study we tested the prediction that an increase in the
      gastrointestinal nematode Heligmosomoides polygyrus would increase the
      infestation of the tick Ixodes ricinus, in free-living yellow-necked mice,
      Apodemus flavicollis. An extensive cross-sectional trapping survey identified a
      negative relationship between H. polygyrus and I. ricinus counter to the
      prediction. An experimental reduction of the nematode infection through
      anthelmintic treatment resulted in an increase in tick infestation, suggesting
      that this negative association was one of cause and effect. Host characteristics
      (breeding condition and age) and habitat variables also contributed to affect
      tick infestation. While these results were counter to the prediction, they still
      support the hypothesis that interactions between parasite species can shape
      parasite community dynamics in natural systems. Laboratory models may act
      differently from natural populations and the mechanism generating the negative
      association is discussed.

PMID- 19154652
TI  - Rodents as shared indicators for zoonotic parasites of carnivores in urban
      environments.
AB  - Rodents are shared intermediate or paratenic hosts for Echinococcus
      multilocularis, Toxocara spp. and Toxoplasma gondii, and may serve as valuable
      indicators for assessing the occurrence and the level of environmental
      contamination and infection pressure with free-living stages of these zoonotic
      parasites. We investigated 658 non-commensal rodents for parasite infections in
      the canton of Geneva, Switzerland. The prevalence of infection with E.
      multilocularis was highest in Arvicola terrestris captured in the north-western
      area (16.5%, CI: 10.1%-24.8%), possibly reflecting a higher red fox density due
      to the low incidence of sarcoptic mange in this part of the canton. The exposure
      rate to Toxocara spp. was highest in the urban area (13.2%, CI: 7.9%-20.3%), and
      may account for higher densities of domestic carnivore and red fox definitive
      hosts within the city. Exposure to T. gondii was widespread (5.0%, CI: 3.2-7.4%),
      indicating a ubiquitous distribution of infected cat definitive hosts.
      Interestingly, a widespread distribution of Taenia taeniaeformis, a parasite
      mainly transmitted by cats, was similarly evidenced in A. terrestris. Distinct
      spatial patterns for the different zoonotic parasites likely reflected
      differences in distribution, abundance, and habitat use of the respective
      definitive hosts. These results highlight the potential value of rodents as
      shared indicators for these pathogens.

PMID- 19154653
TI  - Molecular detection of benzimidazole resistance in Haemonchus contortus using
      real-time PCR and pyrosequencing.
AB  - Benzimidazoles (BZ) are widely used to treat parasitic nematode infections of
      humans and animals, but resistance is widespread in veterinary parasites. Several
      polymorphisms in beta-tubulin genes have been associated with BZ-resistance. In
      the present study, we investigated beta-tubulin isotype 1 sequences of 18
      Haemonchus contortus isolates with varying levels of resistance to thiabendazole.
      The only polymorphism whose frequency was significantly increased in the
      resistant isolates was TTC to TAC at codon 200. Real-time PCR (using DNA from 100
      third-stage larvae, L3s) and pyrosequencing (from DNA from 1000-10 000 L3s) were
      used to measure allele frequencies at codon 200 of these isolates, producing
      similar results; drug sensitivity decreased with increasing TAC frequency.
      Pyrosequencing was also used to measure allele frequencies at positions 167 and
      198. We showed that such measurements are sufficient to assess the BZ-resistance
      status of most H. contortus isolates. The concordance between real-time PCR and
      pyrosequencing results carried out in different laboratories indicated that these
      tools are suitable for the routine diagnosis of BZ-resistance in H. contortus.
      The molecular methods were more sensitive than the 'egg hatch test', and less
      time-consuming than current in vivo- or in vitro-anthelmintic resistance
      detection methods. Thus, they provide a realistic option for routine molecular
      resistance testing on farms.

PMID- 19154654
TI  - A novel phylogeny for the genus Echinococcus, based on nuclear data, challenges
      relationships based on mitochondrial evidence.
AB  - The taxonomic status of Echinococcus, an important zoonotic cestode genus, has
      remained controversial, despite numerous attempts to revise it. Although
      mitochondrial DNA (mtDNA) has been the source of markers of choice for
      reconstructing the phylogeny of the genus, results derived from mtDNA have led to
      significant inconsistencies with earlier species classifications based on
      phenotypic analysis. Here, we used nuclear DNA markers to test the phylogenic
      relationships of members of the genus Echinococcus. The analysis of sequence data
      for 5 nuclear genes revealed a significantly different phylogeny for Echinococcus
      from that proposed on the basis of mitochondrial DNA sequence data, but was in
      agreement with earlier species classifications. The most notable results from the
      nuclear phylogeny were (1) E. multilocularis was placed as basal taxon, (2) all
      genotypes of Echinococcus granulosus grouped as a monophyletic entity, and (3)
      genotypes G8 and G10 clustered together. We conclude that the analysis of nuclear
      DNA data provides a more reliable means of inferring phylogenetic relationships
      within Echinococcus than mtDNA and suggest that mtDNA should not be used as the
      sole source of markers in future studies where the goal is to reconstruct a
      phylogeny that does not only reflect a maternal lineage, but aims to describe the
      evolutionary history at species level or higher.

PMID- 19154655
TI  - Sensitivity of pooled serum testing for screening antibody of schistosomiasis
      japonica by IHA in a mountainous area of Yunnan, China.
AB  - Pooled sample testing (PST) as a strategy for avoiding testing the majority of
      individual negative samples has been proposed for screening of diseases in low
      prevalence areas. There has been no standard guideline for PST in screening of
      Schistosoma japonicum infection of Yunnan, China. To document the optimum pool
      size with acceptable sensitivity of PST for screening of Schistosoma japonicum
      infection in this setting, an experimental pooling of each of 31 positive sera by
      IHA with various numbers of 24 negative sera was done. The results were used to
      create a statistical model which was subsequently used for simulation to predict
      sensitivity of the pooled serum tests in the population with varying prevalence
      and pool size. We found that to keep the sensitivity of PST above 90%, 1:05
      should be the maximum dilution, that is, the optimum pool size should not be
      greater than 6. Antigen will have rather little interference if the prevalence of
      infection is low e.g. 1% or the antigen:antibody ratio is 1:100 or below. Pooled
      serum testing by IHA is an acceptable sensitive method for detecting antibody for
      Schistosoma japonicum infection in this area.

PMID- 19154656
TI  - Haloperidol counteracts the ketamine-induced disruption of processing negativity,
      but not that of the P300 amplitude.
AB  - Antagonists of the N-methyl-D-aspartate (NMDA) receptors such as ketamine, induce
      abnormalities in healthy subjects similar to those found in schizophrenia.
      However, recent evidence, suggests that most of the currently known NMDA
      antagonists have a broader receptor profile than originally thought. Besides
      exerting an antagonistic effect on NMDA receptors, they have agonistic effects on
      dopamine D2 receptors. Can haloperidol (D2 antagonist) counteract the disruptive
      effects of ketamine on psychophysiological parameters of human attention? In a
      randomized, double-blind, placebo-controlled experiment 18 healthy male
      volunteers received placebo/placebo, placebo/ketamine (0.3 mg/kg i.v.) and
      haloperidol (2 mg)/ketamine (0.3 mg/kg i.v.) on three separate test days, after
      which they were tested in an auditory selective-attention paradigm.
      Haloperidol/ketamine reduced task performance compared to placebo/placebo, while
      the task performance in these two treatments did not differ from
      placebo/ketamine. Furthermore, placebo/ketamine reduced processing negativity
      compared to both placebo/placebo and haloperidol/ketamine, while processing
      negativity did not differ between placebo/placebo and haloperidol/ketamine
      treatments. However, both placebo/ketamine and haloperidol/ketamine reduced P300
      amplitude compared to placebo/placebo, while P300 amplitude did not differ
      between placebo/ketamine and haloperidol/ketamine treatments. The combined
      effects of haloperidol and ketamine reduced task performance, suggesting that
      this is dependent on dopaminergic D2 activity, probably in the prefrontal cortex.
      In addition, ketamine reduced both P300 amplitude and processing negativity. In
      contrast to the P300 amplitude, the disruptive effects of ketamine on processing
      negativity could be prevented by pretreatment with haloperidol. The current
      results suggest that ketamine reduced P300 amplitude by its antagonistic effect
      on glutamatergic activity, while it reduced processing negativity by its
      agonistic effect on dopaminergic D2 activity.

PMID- 19154657
TI  - Association between golli-MBP and schizophrenia in the Jewish Ashkenazi
      population: are regulatory regions involved?
AB  - Multiple studies have reported oligodendrocyte and myelin abnormalities, as well
      as dysregulation of their related genes, in brains of schizophrenia patients. One
      of these genes is the myelin-basic-protein (MBP) gene, which encodes two families
      of proteins: classic-MBPs and golli-MBPs. While the classic-MBPs are
      predominantly located in the myelin sheaths of the nervous system, the golli
      proteins are more widely expressed and are found in both the immune and the
      nervous systems. In the present study we performed a case-control association
      analysis of golli-MBP in two separate Jewish Ashkenazi cohorts (cohort I: 120
      patients, 236 controls; cohort II: 379 patients, 380 controls). In addition we
      performed an expression analysis of golli-MBP mRNA in post-mortem dorsolateral
      prefrontal cortex samples of schizophrenia patients, and matched controls. In the
      first cohort we observed association between six (out of 26 genotyped) single
      nucleotide polymorphisms (SNPs) and the disease (p<0.05). Of these, three are
      from one linkage disequilibrium (LD) block which contains a CTCF binding region.
      Haplotype analysis revealed significant 'risk'/'protective' haplotypes (strongest
      p=0.005, each) for schizophrenia. The three SNPs (rs12458282, rs2008323,
      rs721286) were then genotyped in the second cohort. The combined results showed
      strong effects, both in the single marker and in haplotype analyses (strongest OR
      1.77, p=0.0005; OR 1.61, p=0.00001, respectively). Sequencing the CTCF binding
      region revealed three SNPs in complete LD with the associated haplotypes, located
      in close proximity to the CTCF binding site. Expression analysis found no
      significant differences in golli-MBP mRNA levels. These findings suggest that
      golli-MBP is a possible susceptibility gene for schizophrenia.

PMID- 19154658
TI  - Anagrelide for the treatment of essential thrombocythemia: a survey among
      European hematologists/oncologists.
AB  - Two hundred and fifty hematologists and oncologists (50 each from France,
      Germany, Italy, Spain and the United Kingdom) participated in this survey to
      assess the current management of essential thrombocythemia (ET), with particular
      reference to the use of anagrelide. Data were collected between October 9 and
      November 2, 2006 on 2000 patients with ET. Thirty-eight per cent of patients had
      been tested for the Janus kinase 2 (JAK2) mutation (JAK2V617F), of whom 54%
      tested positive. JAK2V617F mutation status was not influenced by age, gender or
      cardiovascular risk. Overall, 297 patients (14.9%) were receiving anagrelide
      hydrochloride; 16.8% of these patients were aged 18-40 years, 43.1% aged 41-60
      years and 40.1% aged over 60 years. Hydroxycarbamide, alone or in combination
      with aspirin, was the most commonly prescribed treatment in 136/191 (71.2%)
      patients prior to switching to anagrelide. In conclusion, this survey provides a
      useful insight into the epidemiology of ET and current prescribing patterns for
      anagrelide in Europe.

PMID- 19154659
TI  - Limited efficacy of hydroxyurea in lowering of the JAK2 V617F allele burden.
AB  - Besides being an invaluable marker of clonal disease in chronic
      myeloproliferative disorders (CMPDs), the JAK2 V617F mutation and the mutated
      allele burden have an impact on disease phenotype and may provide information on
      prognosis. Recently, hydroxyurea (HU) has been shown to induce a rapid decline in
      the JAK2 V617F allele burden. The aim of the present study was to assess the
      dynamics of the JAK2 V617F allele burden during long-term treatment with HU in a
      series of patients with CMPDs. The JAK2 V617F allele burden was determined by
      quantitative PCR in 24 patients of whom 17 received HU, four received anagrelide
      and three were followed without any cytoreductive therapy. During a median follow
      up of 24.2 months, no significant reductions in the JAK2 V617F allele burden were
      seen in patients treated with HU. We conclude that HU has only a limited effect
      on the JAK2 V617F allele burden in CMPD.

PMID- 19154660
TI  - Bone marrow angiogenesis in aplastic anemia--a study of CD 34 and VEGF expression
      in bone marrow biopsies.
AB  - INTRODUCTION: Bone marrow function and the growth of hemopoietic cells depends on
      an intact microvasculature. A pivotal regulator of angiogenesis is vascular
      endothelial growth factor (VEGF). Our study assesses VEGF expression and
      microvessel density (MVD) in the bone marrow of patients with aplastic anemia
      (AA). MATERIALS AND METHOD: Bone marrow specimens from 25 patients with AA and 15
      controls were studied. MVD was calculated on sections stained
      immunohistochemically for CD34. Subsequently, all the cases were studied for VEGF
      expression. RESULTS: Bone marrow MVD in patients with AA was significantly lower
      than that in controls (p < 0.01). There was a significant MVD difference between
      severe AA and moderate AA (p < 0.05). VEGF expression was also significantly
      lower in AA cases compared to controls (p < 0.05). CONCLUSION: Our data show that
      AA is associated with reduced angiogenesis and reduced VEGF expression. Defective
      angiogenesis may result in or aggravate bone marrow aplasia in AA patients. There
      are limited studies on this aspect. More studies to confirm the present
      hypothesis might pave the way for new treatment options in AA.

PMID- 19154661
TI  - Management of transfusional iron overload in Latin America: current outlook and
      expert panel recommendations.
AB  - The results of a meeting of physicians convening in Latin America to develop
      expert opinions on the diagnosis, monitoring and treatment of iron overload are
      as follows. An accurate diagnosis can be obtained by neonatal screening for
      haemoglobinopathies, especially sickle cell disease and the thalassaemias.
      Disease-specific registries are needed to demonstrate the extent of the problem
      to health authorities. Disparities in the quantity and quality of blood products
      must be addressed, and uniform transfusion guidelines are necessary. Serum
      ferritin level is a feasible marker for iron overload in the region, while
      magnetic resonance imaging assessment can improve the diagnosis and monitoring of
      cardiac and liver iron content. Medical specialists, including radiologists,
      pathologists and others, and health authorities, can help to implement these
      methods and provide adequate resources. The recently available oral deferasirox
      can be used to conveniently administer iron chelation to transfusional iron
      overloaded patients.

PMID- 19154662
TI  - Abnormalities in the expression of CD55 and CD59 surface molecules on peripheral
      blood cells are not specific to paroxysmal nocturnal hemoglobinuria.
AB  - The regulatory proteins CD55 and CD59 are glycolsylphosphatidylinositol-anchored,
      type I cell surface proteins, which inhibit formation of the C3 convertases and
      prevent the terminal polymerization of the membrane attack complexes,
      respectively. Paroxysmal nocturnal hemoglobinuria (PNH) is a genetic disorder due
      to the impaired conformation of the glycolsylphosphatidylinositol anchor, which
      results in the deficient expression of CD55 and CD59 leading to excessive
      destruction of red cells and leukocytes. We have studied the expression of these
      two molecules in red blood cells, granulocytes and platelets in patients with PNH
      (two patients), autoimmune hemolytic anemia (AIHA) (seven patients), autoimmune
      thrombocytopenia (ATP) (22 patients), systemic lupus erythematosus (SLE) (19
      patients), aplastic anemia (AA) (eight patients), and Evans syndrome (ES) (two
      patients). A diminished expression of CD55 and CD59 was found in the three cell
      lines of the two patients with PNH. In the seven patients with AIHA two were
      found with CD59 diminished expression in red blood cells and one with CD59
      diminished expression in granulocytes. In the patients with ATP one was found
      with CD55 diminished expression in red blood cells, one with CD59 diminished
      expression granulocytes and one with a CD59 diminished expression in the
      platelets. In the subset of patients with SLE only one was found with a CD55
      diminished expression in the red blood cells. In the patients with AA, a
      diminished expression in red blood cells was not found; however, one patient was
      found with a diminished expression of CD59 in granulocytes, and one patient with
      a diminished expression of CD55 in the platelets. In the two patients with ES we
      did not found changes in the expression of CD55 and CD59. We conclude that the
      diminished expression of the glycolsylphosphatidylinositol-anchored type I cell
      surface proteins CD55 and CD59 is not specific to PNH and that it can be found in
      patients with a variety of autoimmune disorders. Additional studies are needed to
      define the role of the deficiencies of CD55 and CD59 in the pathogenesis of
      autoimmune hemocytopenias.

PMID- 19154663
TI  - Effect of glucose-6-phosphate dehydrogenase deficiency on some biophysical
      properties of human erythrocytes.
AB  - The most widespread erythrocyte enzyme defect throughout the world is glucose-6
      phosphate dehydrogenase (G-6-PD) deficiency. The diagnosis of G-6-PD deficiency
      may be missed during an acute hemolytic episode due to increased young red blood
      cells which have good enzyme activity. However this might be detected at a later
      stage when the patient is asymptomatic. This calls for a detailed investigation
      of the patient with an acute attack of hemolysis at a later stage. Blood samples
      were obtained from 45 G-6-PD deficient male patients with previously diagnosed
      disease [25 subjects were during hemolytic attack (Gp1) while the rest was
      outside acute hemolytic crisis (Gp2)] and 20 healthy male subjects. The effect of
      G-6-PD deficiency on the erythrocytes of the above groups was investigated by
      scanning electron microscope (SEM) complemented with dielectric spectroscopy. The
      quantification of the morphological shape changes revealed that Gp1 had a
      significant increase in spheroechinocytes as well as in the morphological index
      in comparison with those of all other groups. The overall electrical and
      morphological properties of the red cell membrane of these subjects modified to a
      great extent during hemolytic attack. This may have important diagnostic and
      research implications. Thus the combined application of dielectric spectroscopy
      and SEM can be used as an efficient manner for monitoring abnormalities in blood
      and erythrocytes due to G-6-PD deficiency.

PMID- 19154664
TI  - Near-infrared spectra absorbance of blood from sickle cell patients and normal
      individuals.
AB  - Limited data are available regarding the physicochemical dynamics of tissue
      hypoxia in sickle cell disease. Studies using near-infrared spectroscopy (NIRS)
      have reported that patients with sickle cell disease (SCD) have lower cerebral
      oxygen saturation values (rSO2) than normal individuals. The reason SCD patients
      have subnormal rSO2 values is not known. It may be related to the degree of
      anaemia, sickle haemoglobin, disease complications and the possibility of SCD
      different NIRS absorbance spectra than normal. This study compared NIRS
      absorbance spectra of blood with adult haemoglobin AA, sickle haemoglobin SS, and
      AS. Venous blood was collected from SCD (SS and AS) and non-SCD patients (AA).
      Whole blood, cell free haemoglobin samples were scanned through the wavelength
      range of 600-1000 nm. The results showed no different NIRS spectra absorbance
      between the haemoglobin's AA, SS. It thus appears that lower brain oxygen
      saturation in sickle cell anaemia patients is related to impaired oxygen carrying
      capacity or delivery by sickle haemoglobin.

PMID- 19154665
TI  - Autoimmune thrombocytopenia related to chronic hepatitis C virus infection.
AB  - Since the identification of hepatitis C virus (HCV) in 1989 as a causative agent
      for a number of the extrahepatic alterations related to HCV infection an
      underlying immune mediated pathogenetic mechanism has been postulated. HCV
      associated thrombocytopenia may be considered complex and multifactorial in
      origin, since different mechanisms have been implicated in its pathophysiology.
      With respect to autoimmune thrombocytopenia in chronic HCV infection, the
      detection of specific antibodies against platelet glycoproteins have been
      reported only in a few studies, but no systematic study has been carried out. We
      examined the clinical, laboratory, and virological characteristics of a case
      series of 10 patients with autoimmune thrombocytopenia (platelet count <150.0 x
      10(9)/L) related to chronic HCV infection. Cases, six males and four females,
      aged 57.1 +/- 12.6 years, presented high titers of antibodies against platelet
      glycoprotein (GP) IIb/IIIa, GP Ia/IIa, and/or GP Ib/IX, and no other mechanism
      involved in the pathogenesis of HCV-associated thrombocytopenia was identified.
      Furthermore, cases were not associated with particular HCV genotype. Complete
      platelet response was observed in two patients treated with pegylated interferon
      plus ribavirin, and partial platelet response was seen in two patients treated
      with anti-D Ig and one patient treated with corticosteroids. These findings
      indicate that an autoimmune mechanism may play a role in the pathogenesis of HCV
      associated thrombocytopenia in a proportion of these patients.

PMID- 19154666
TI  - Nitric oxide in immune thrombocytopenic purpura.
AB  - Nitric oxide (NO), initially described as the endothelial derived relaxation
      factor, is an important messenger molecule involved in many physiological and
      pathological processes. Endothelium-derived NO causes vasorelaxation and also
      inhibits platelet adhesion and aggregation, thus maintaining blood fluidity and
      preventing thrombosis. As such, this molecule has been extensively studied in
      cardiology for its role in atherosclerosis and ischemic heart disease. An
      important alternate function of NO is in the modulation of platelet production
      from the megakaryocytes. Immune thrombocytopenic purpura (ITP) can be associated
      with a decrease in NO bioavailability which contributes to the thrombocytopenia
      and other clinical characteristics associated with this condition. At the same
      time, some of the treatment modalities for ITP may be exerting their beneficial
      effects by increasing the levels of NO and thus improving platelet production.

PMID- 19154667
TI  - Surface-engineered dendrimers: a solution for toxicity issues.
AB  - The nature of the groups that reside on the periphery of dendrimers and have
      contact with the surrounding media is the primary factor that controls the
      surface-related physico-chemical characteristics of these macromolecules.
      Therefore, transformation/tailoring of the peripheral functionalities of
      dendrimers is an economical way to change the overall behaviour of a particular
      dendrimer class or to impart new properties. In addition, the yields of the
      completely modified macromolecules could provide valuable information for the
      accessibility and the back folding of the moieties placed at the dendritic
      surfaces. The present article reviews the parent toxicity issues associated with
      cationic dendrimers like PAMAM and PPI, and examines the possibility of
      addressing this aspect through surface engineering with conjugation of
      biocompatible molecules.

PMID- 19154668
TI  - Human alveolar bone-derived cell-culture behaviour on biodegradable poly(L-lactic
      Acid).
AB  - Poly(L-lactic acid) (PLA) is a polymer of great technological interest, whose
      excellent mechanical properties, thermal plasticity and bioresorbability render
      it potentially useful for environmental applications, as a biodegradable plastic
      and as a biocompatible material in biomedicine. The interactions between an
      implant material surface and host cells play central roles in the integration,
      biological performance and clinical success of implanted biomedical devices.
      Osteoblasts from human alveolar bone were chosen to investigate the cell
      behaviour when in contact with PLA discs. Cell morphology and adhesion through
      osteopontin (OPN) and fibronectin (FN) expression were evaluated in the initial
      osteogenesis, as well as cell proliferation, alkaline phosphatase activity and
      bone nodule formation. It was shown that the polymer favoured cell attachment.
      Cell proliferation increased until 21 days but in a smaller rate when compared to
      the control group. On the other hand, ALP activity and bone mineralization were
      not enhanced by the polymer. It is suggested that this polymer favours cell
      adhesion in the early osteogenesis in vitro, but it does not enhance
      differentiation and mineralization.

PMID- 19154669
TI  - Synthesis and characterization of Zwitterionic co-polymers as matrices for
      sustained metoprolol tartrate delivery.
AB  - Very stable co-polymer (vinyl acetate (VA)-co-3-dimethyl(methacryloyloxyethyl)
      ammonium propane sulfonate (DMAPS) (p(VA-co-DMAPS)) latexes with different
      compositions have been synthesized by emulsifier-free emulsion co-polymerization.
      The dry p(VA-co-DMAPS)s have been used in the preparation of drug tablets for
      sustained Metoprolol tartrate release. It has been shown that the tablet swelling
      depends on the mol fraction of DMAPS monomer units (m(DMAPS)), pH and ionic
      strength (I). An original explanation, based on the swelling behavior of p(VA-co
      DMAPS), has been proposed for the "overshooting" phenomenon observed. It assumes
      the formation of hydrophilic domains with a higher m(DMAPS) in the co-polymer
      tablets. The formation of dipole-dipole clusters between the DMAPS units at
      different m(DMAPS) and I are the main cause for the established differences in
      both the swelling kinetics of the p(VA-co-DMAPS) matrices and Metoprolol tartrate
      release. The obtained results show that for p(VA-co-DMAPS) matrices-based tablets
      controlled sustained Metoprolol tartrate release can be realized just by varying
      two parameters, co-polymer composition and I.

PMID- 19154670
TI  - A low-temperature thermoplastic anti-bacterial medical orthotic material made of
      shape memory polyurethane ionomer: influence of ionic group.
AB  - PCL-based shape memory polyurethane ionomers with quaternarized pyridine moieties
      incorporated through molecular extension were synthesized. These polyurethanes
      were specifically designed as low-temperature thermoplastic anti-bacterial
      orthotic materials. A commercialized orthotic material was employed for
      comparison. The influence of ionic groups on the properties of orthotic materials
      was studied. The anti-bacterial properties and cytotoxicity of the polyurethane
      ionomer were tested. It was found that, different from other researchers'
      conclusions, the Coulombic force among cationic groups and the increased cohesion
      among hard segments after ionization could lead to polyurethane with better phase
      separation, soft segment phase crystallability and hard segment phase stability.
      The results of this work indicated that, although the ionic group had the
      function of improving phase separation, the asymmetric extender had a negative
      effect on the hard segment phase stability. Several of the main physical
      properties of the synthesized polyurethane as orthortic materials were studied.
      The materials mechanical properties at using temperature (ambient temperature 22
      degrees C) were improved so it may be used in circumstances where high mechanical
      strength is required. The fixity ratio was increased; as a result the material
      may fix shape more precisely according to patient affected parts. At last, a
      prototype wrist orthotic device was fabricated by hands. The orthotic device
      percent reductions against Klebsiella pneumoniae and Staphylococcus aureus were
      96.2% and 100%, respectively. The anti-bacterial activity rating of this device
      was acceptable and significant according to ASTM E 2149. Cytotoxicity tests
      indicated that the wrist orthotic material was not cytotoxic.

PMID- 19154671
TI  - Extruded collagen fibres for tissue-engineering applications: influence of
      collagen concentration and NaCl amount.
AB  - Extruded collagen fibres have been shown to be a competitive biomaterial for
      tissue-engineering applications. Since different tissues are coming in different
      textures, as far as it is concerned their fibre diameter and consequently their
      mechanical properties, herein we aim to investigate the influence of the collagen
      concentration and the amount of NaCl on the properties of these fibres. Scanning
      electron microscopy study revealed that the substructure of the collagen fibres
      was the same, regardless of the treatment. The thermal properties were found to
      be independent of the collagen concentration or the amount of NaCl utilized (P >
      0.05). An inversely proportional relationship between dry fibre diameter and
      stress at break was observed. Increasing the collagen concentration yielded
      fibres with significant higher diameter (P < 0.002), strain (P < 0.009) and force
      (P < 0.001) values, whilst the stress (P < 0.008) and modulus (P < 0.009) values
      were decreased. For the fabrication of fibres with reproducible properties, 20%
      NaCl was found to be the optimum. Overall, reconstituted collagen fibres were
      produced with properties similar to native or synthetic fibres to suit a wide
      range of tissue-engineering applications.

PMID- 19154672
TI  - Polyacrylamide-grafted-alginate-based pH-sensitive hydrogel beads for delivery of
      ketoprofen to the intestine: in vitro and in vivo evaluation.
AB  - A pH-sensitive graft co-polymer of polyacrylamide (PAAm) and sodium alginate (SA)
      was synthesized by free radical polymerization under a nitrogen atmosphere
      followed by alkaline hydrolysis. The co-polymer was characterized by Fourier
      transform infrared (FT-IR) spectroscopy, elemental analysis and thermogravimetric
      analysis (TGA). Ketoprofen-loaded graft co-polymer beads were prepared by
      ionotropic gelation/covalent cross-linking. The beads were characterized by
      swelling studies, differential scanning calorimetry (DSC) and scanning electron
      microscopy (SEM). A pulsatile swelling study indicated that the co-polymer
      exhibits considerable pH-sensitive behavior. Release of ketoprofen was
      significantly increased when the pH of the medium was changed from acidic to
      alkaline. Stomach histopathology of albino rats indicated that the beads were
      able to retard the release of the drug in the stomach, and gastric side-effects
      like ulceration, hemorrhage and erosion of gastric mucosa were diminished when
      the drug was entrapped into PAAm-g-SA-based pH-sensitive hydrogel beads.

PMID- 19154673
TI  - Tyrosinase-catalysed coating of wool fibres with different protein-based
      biomaterials.
AB  - The potential of tyrosinases to activate tyrosine residues of wool protein fibres
      for cross-linking with different materials like collagen, elastin and gelatine
      was assessed. Natural fibres like wool offer an excellent environment for the
      growth of micro-organisms when the conditions like moisture, oxygen and
      temperature are appropriate. Coating with collagen, a very useful biomaterial
      with bactericidal and fungicidal properties, could be used to improve the
      properties of wool-based materials, especially when applied in hygienically
      sensitive applications like in hospitals. Tyrosinases were shown to catalyse the
      oxidation of tyrosine residues in wool and wool hydrolysates as model substrates,
      as determined by UV-Vis spectroscopy. Structural differences of the surface were
      evident from the increase of the intensity in the NH bending and stretching
      regions in the spectra of NIR FT Raman analysis of the enzyme treated and grafted
      wool fibres. The durability of the coating was also shown by using FITC-labelled
      collagen that was bound to the wool fibres, even after severe washing.
      Additionally, antimicrobial properties were successfully imparted due to the
      collagen grafted on the wool fibres. The functional and mechanical properties of
      the treated wool fibres showed no significant changes.

PMID- 19154680
TI  - [Medecine/Sciences as time goes by].

PMID- 19154681
TI  - [APRIL, the spring of plasmacytes].

PMID- 19154682
TI  - [When cancer cells are addicted to a regular gene].

PMID- 19154683
TI  - [The novel function of the tumor suppressor APC in recruiting polarized RNAs in
      migrating cells].

PMID- 19154684
TI  - [Grafted dopaminergic neurons are targeted by the disease process in Parkinson's
      disease].

PMID- 19154685
TI  - [Pinwheel architecture of neural stem cell niche, the third dimension].

PMID- 19154686
TI  - [NPM: a new player in prostate cancer?].

PMID- 19154687
TI  - [Regulation of plasticity in the auditory cortex by sensory experience].

PMID- 19154688
TI  - [A new promising drug against schistosomiasis].

PMID- 19154689
TI  - [Nephrocytes and podocytes, even fight?].

PMID- 19154690
TI  - [The key implication of early migration of metastatic cells].

PMID- 19154692
TI  - [Cell-derived microparticles unveil their fibrinolytic and proteolytic function].
AB  - Cell-derived microparticles (MP) are membrane microvesicles, 0.1-1 microm in
      size, shed by cells following activation or during apoptosis in a variety of
      pathological conditions. MPs released by blood cells or by vascular endothelial
      cells display molecular signatures that allow their identification and functional
      characterization. In addition, they provide tissue factor (TF) and a procoagulant
      phospholipid surface. Therefore, at present, the most strongly established
      applied research on MPs is their procoagulant activity as a determinant of
      thrombotic risk in various clinical conditions. Previous studies have indicated
      that MPs derived from malignant cells express matrix metalloproteinases,
      urokinase and its receptor (uPA/uPAR) that, in the presence of plasminogen, may
      act in concert to degrade extracellular matrix proteins. Recently, it was shown
      that MPs from TNFa-stimulated endothelial cells served as a surface for
      interaction with plasminogen and its conversion into plasmin by the uPA/uPAR
      system expressed at their surface. This capacity of MPs to promote plasmin
      generation confers them a new profibrinolytic and proteolytic function that may
      be of relevance in fibrinolysis, cell migration, angiogenesis, dissemination of
      malignant cells, cell detachment and apoptosis.

PMID- 19154693
TI  - [The two sides of ADAM17 in inflammation: implications in atherosclerosis and
      obesity].
AB  - ADAM17 was initially characterized as the TNF Alpha Converting Enzyme (TACE) and,
      until now, has been the most studied member of the ADAM family. It is a type I
      transmembrane metalloproteinase involved in the shedding of the extracellular
      domain of several transmembrane proteins (at least 40) such as cytokines, growth
      factors, receptors or adhesion molecules. As a consequence, depending on the
      transmembrane molecule cleaved, one may expect possible opposite effects of
      ADAM17 activity on inflammation (e.g. TNF and its receptors). The role of ADAM17
      in regulating inflammatory cellular processes is clearly demonstrated in cells
      deficient in active ADAM17 or expressing substrates mutated for the ADAM17
      cleavage site. As ADAM17-deficient mice died at birth, mice overexpressing the
      mutated uncleavable form of some substrates and recently conditional knock-out of
      ADAM17 are used to approach in vivo the role of this metalloprotease in
      regulating inflammation. Arguments are provided that ADAM17 plays a role in
      atherosclerosis, in adipose tissue metabolism, insulin resistance and diabetes.
      The multitude of substrates cleaved by ADAM17 makes this enzyme an attractive
      candidate to study its role in inflammation-driven pathologies.

PMID- 19154694
TI  - [Polyunsaturated fatty acids: anticonvulsive effects and underlying mechanisms].
AB  - Omega-3 and omega-6 poly-unsaturated fatty acids (PUFA) are the major families of
      PUFA that can be found as components of the human diet. After ingestion, both
      omega-3 and omega-6 PUFA are distributed to every cell in the body where they are
      involved in a myriad of physiological processes, including regulation of
      cardiovascular, immune, hormonal, metabolic, neuronal, and visual functions. At
      the cellular level, these effects are mediated by changes in membrane
      phospholipids structure, by interference with eicosanoid intracellular signaling,
      and by regulation of gene expression. The literature suggests the antiepileptic
      properties of PUFA, although these evidences emerge from basic science rather
      than from clinical trials. Several hypotheses have been suggested to explain the
      anticonvulsive effects of PUFA: modification of the membrane fluidity, direct
      action of PUFA on cell membrane ionic channels and/or receptors, modulation of
      inflammatory responses. Regarding the published clinical trials, the data are
      conflicting. It is currently not known whether different doses or different omega
      3: omega-6 ratios would be effective.

PMID- 19154695
TI  - [New regulatory and signal functions for myristic acid].
AB  - Myristic acid is a 14 carbon saturated fatty acid, which is mostly found in milk
      fat. In industrialized countries, its excessive consumption is correlated with an
      increase in plasma cholesterol and mortality due to cardiovascular diseases.
      Nevertheless, one feature of this fatty acid is its ability to acylate proteins,
      a reaction which is called N-terminal myristoylation. This article describes
      various examples of important cellular regulations where the intervention of
      myristic acid is proven. Modulations of the cellular concentration of this fatty
      acid and its associated myristoylation function might be used as regulators of
      these metabolic pathways.

PMID- 19154696
TI  - [Anti-CD10 fetomaternal alloimmunisation].
AB  - Fetomaternal alloimmunization with antenatal glomerulopathies (FMAIG) is a
      recently described alloimmune disorder, which results from the production of
      maternal antibodies that cross the placenta, bind to fetal glomerular podocytes,
      and mediate renal disease. The pathogenic antibodies are directed against
      CD10/neutral endopeptidase (NEP). The infant's mother is NEP-deficient and thus
      she becomes immunized during the first pregnancy against CD10/NEP expressed by
      placental cells. Because future pregnancies in CD10/NEP-immunized mothers are at
      high risk for the fetus, detection of anti-NEP antibodies in pregnant mothers and
      antigen-driven therapies including induction of tolerance, are urgently needed.
      This ideally requires identification of the pathogenic epitopes born by the
      antigen and specifically recognized by B- and T-cells. We have recently
      characterized such epitopes that will be used in diagnostic tests (ELISA) and for
      new therapeutic approaches based on peptide-specific immune intervention. For
      this purpose, we have developed an experimental model by crossing NEP/CD10
      deficient female mice to wild-type males. The females develop an alloimmune
      reaction against NEP, which is a prerequisite for tolerance induction
      experiments. Although NEP/CD10 does not seem to be involved in common idiopathic
      forms of membranous nephropathy in the adult, alloimmune antibodies may be
      implicated in de novo membranous nephropathy that develop in the kidney graft and
      after alloimmune bone marrow transplantation.

PMID- 19154697
TI  - [Diamond-Blackfan anemia reveals the dark side of ribosome biogenesis].
AB  - Diamond-Blackfan anemia (DBA), a rare congenital erythroblastopenia, has recently
      become a paradigm for a growing set of genetic diseases linked to mutations in
      genes encoding ribosomal proteins or factors involved in ribosome biogenesis.
      Recent studies of the structure and the function of ribosomal proteins affected
      in DBA indicate that their mutation in DBA primarily impacts ribosome biogenesis.
      Accordingly, cells from DBA patients display anomalies in the maturation of
      ribosomal RNAs. The explanation of this unexpected link between ribosome
      biogenesis, a ubiquitous process, and a disease mostly affecting erythroid
      differentiation may stem in part from the emerging concept of ribosomal stress
      response, a signaling pathway triggering cell cycle arrest in response to a
      defect in ribosome synthesis. Future studies of DBA and other diseases related to
      defects in ribosome biogenesis are likely to rapidly provide important insights
      into the regulatory mechanisms linking cell cycle progression to this major
      metabolic pathway.

PMID- 19154698
TI  - [Hoxa5: a master gene with multifaceted roles].
AB  - The Hox gene family occupies a central position in the control of body patterning
      by regulating the transcription of downstream effectors that, in turn, direct the
      morphogenetic events leading to the complex body forms along the axes. Analysis
      of Hox mutant mouse lines has revealed a panoply of phenotypes indicative of the
      broad range of Hox genes action throughout embryonic and postnatal life. Although
      Hox genes have been the subject of extensive research in the last two decades,
      the comprehension of the mechanisms involved in their regulation and function
      still remains elusive. Here, we present an overview of our current knowledge
      about one Hox gene family member, Hoxa5. The phenotypic survey of Hoxa5 mutant
      mice has unveiled the crucial role of this gene in regulating morphogenesis and
      specifying regional identity along the embryo. A majority of Hoxa5 mutant pups
      die at birth from defective respiratory tract. Surviving mutants present
      deficient alveolar septation revealing the importance of Hoxa5 during formation
      and maturation of the lung. Hoxa5 also participates in the morphogenesis of the
      digestive tract as well as that of the thyroid and mammary glands. Hoxa5
      expression is restricted to the mesenchyme, and its action appears to be mediated
      through the control of mesenchymal-epithelial interactions during organogenesis.
      The implication of Hoxa5 in tumorigenesis has also been documented. In breast
      cancer, Hoxa5 down-regulation may impact on p53 gene expression, contributing to
      the oncogenic process. In contrast, the loss of Hoxa5 function limits leukaemia
      associated with specific chromosomal translocations. Thus, inappropriate Hoxa5
      gene expression may disrupt normal growth and differentiation programs causing
      neoplasia. Hox gene function is intimately linked to its correct expression.
      Regulation of Hoxa5 expression requires multiple cis-acting regions, some
      encompassing coding sequences from neighboring genes. Moreover, it is complicated
      by the presence of several transcription units. Together these data enlighten the
      importance of Hox cluster organization in Hoxa5 function.

PMID- 19154699
TI  - [Violence against persons in France].
AB  - The violence against persons in France are various, from those inflicted by
      society against human groups or individuals, from those, almost unrecognizable,
      occurring inside the families. It is an important public health problem and need
      population-based surveys to evaluate and to prevent it. The numerous publications
      about violence, and particularly about violence against women which have been
      recently published reflect the actual awareness. But they demonstrate also the
      diversity and the evolution of the policies which do not simplify the the ways to
      find solutions.

PMID- 19154700
TI  - [HIV prevalence in sub-Saharan Africa: background of an estimation].
AB  - In 2008 UNAIDS global report on AIDS, the number of people living with HIV in sub
      Saharan Africa was estimated at 22 millions in 2007 and 20.4 millions in 2001,
      while in the 2002 report, the same estimation for 2001 was 28.5 millions. Changes
      in UNAIDS reflects evolutions of data sources and methods used for the estimates.
      Sentinel surveillance of pregnant women attending antenatal clinics (ANC) was
      developed in 1980's with the WHO recommendation of unlinked anonymous testing
      approach. The objective was not to be representative but to monitor trends. In
      the 1990's, as ANC data were available, they were used by EpiModel, a model
      developed by WHO for HIV prevalence estimates from 1992 to 2000. In 2002, a new
      epidemiological model called EPP (Estimation and Projection Package) was
      developed by the UNAIDS Reference Group on Estimates, Modelling and Projections,
      which, in countries with a generalised epidemic, is still based on ANC data
      collected over time. Since 2001, many countries have conducted national
      population-based surveys (NPS). Their results have often diverged from estimates
      based on ANC data. This was explained by the under-representation of rural
      clinics in sentinel surveillance and relative small participation rate in NPS.
      Since, several studies have shown that the impact of several biases
      (participation rate, non-household members, serological window of tests...) in
      NPS remains relatively low. NPS constitute a good indicator of HIV prevalence
      level. If pregnant women can be locally representative of the general population,
      at the national scale, it depends of the localization of selected clinics. But
      ANC provides data over time, which is not the case for NPS. The current approach
      of UNAIDS consists in estimating HIV prevalence trends from ANC and the level of
      the epidemics from NPS. But the hypothesis that ANC data are representative of
      trends still needs to be verified when several NPS will be available for a same
      country.

PMID- 19154701
TI  - [Treatment of information on personal health data for research purposes: nobody
      should ignore the law].

PMID- 19154702
TI  - [A recurrent hotspot of genomic instability identified in human ES cells].

PMID- 19154703
TI  - [Astroglial connexins fuel synapses].

PMID- 19154704
TI  - [In silico, in vitro, in omic experimental models and drug safety evaluation].
AB  - Over the last few decades, toxicology has benefited from scientific, technical,
      and bioinformatic developments relating to patient safety assessment during
      clinical and drug marketing studies. Based on this knowledge, new in silico, in
      vitro, and "omic" experimental models are emerging. Although these models cannot
      currently replace classic safety evaluations performed on laboratory animals,
      they allow compounds with unacceptable toxicity to be rejected in the early
      stages of drug development, thereby reducing the number of laboratory animals
      needed. In addition, because these models are particularly adapted to mechanistic
      studies, they can help to improve the relevance of the data obtained, thus
      enabling better prevention and screening of the adverse effects that may occur in
      humans. Much progress remains to be done, especially in the field of validation.
      Nevertheless, current efforts by industrial, academic laboratories, and
      regulatory agencies should, in coming years, significantly improve preclinical
      drug safety evaluation thanks to the integration of these new methods into the
      drug research and development process.

PMID- 19154705
TI  - [France, an attractive country for international clinical research: 2008 survey
      assessed by Leem (French association of pharmaceutical companies)].
AB  - In order to evaluate the attractiveness of France for conducting international
      clinical trials, a survey is performed every two years among pharmaceutical
      companies that are based in France or have affiliates in France. Nineteen
      companies (61.9 % of the French market) have participated in the current survey
      which included 385 international phase II and III clinical studies, 77 countries,
      29,708 centres and 312,835 patients (included in 2006/2007). France (400
      patients/million inhabitants) ranked among the best European recruiters in second
      position behind Scandinavia. Since 2006, France has improved administrative
      processes and reduced deadlines for hospital contracts. Protocols are now to be
      given the go-ahead by French Authorities (Afssaps and CPP) within 60 days, in
      accordance with European directive. Its performance in early phases,
      oncology/hematology and vaccines/anti-infectious contribute to the attractiveness
      of France in international clinical research.

PMID- 19154706
TI  - [Risperidone use in child and adolescent psychiatric patients].
AB  - In a plural and multidisciplinary process of care, it would be fruitful to ally
      complementary, pharmacologic and psychodynamic approaches. We have done a review
      of the literature on the effectiveness and the cautions for prescription of
      risperidone, a second generation antipsychotic drug. Risperidone has proved
      helpful in treating children and adolescents with autism spectrum, conduct and
      bipolar disorders, Tourette's syndrome, and schizophrenia. The principal side
      effects are sedation, weight gain, and metabolic disturbances. Extrapyramidal
      symptoms, QTc prolongation, and hyperprolactemia with clinical signs are
      infrequent and not clinically significant. The benefit/risk is clearly in favor
      of the prescription when it is accompanied with the precautions and with the
      adequate monitoring.

PMID- 19154707
TI  - [A medical and economic study about use of hemostatic glues in cardiac surgery].
AB  - INTRODUCTION: The impact of the use of biological and synthetic glues in cardiac
      surgery was assessed by an economic and medical study. MATERIAL AND METHODS: The
      observational prospective study had duration of three months. All the patients
      undergoing cardiac surgery were included in the study. The end points were
      medical (blood transfusion) and economic (duration and cost of the stay in
      hospital). There were 2 groups: treated or not by glues. STATISTICAL ANALYSIS: T
      Student tests. RESULTS: Among 154 patients, the 2 principal indications were
      valvular replacement (48%) and coronary artery bypass grafting (37%). Fifty seven
      (37%) patients received a glue. The number of transfused globular units and the
      duration of the stay in the intensive care unit were significantly higher
      (p<0.05) by treated patients. CONCLUSION: Not only the use of glues did not
      decrease the post-operative bleedings but it increased also the cost of the stay
      in hospital. Guidelines were validated by the hospital Commission on drugs.

PMID- 19154708
TI  - [Adverse drug reactions: a pilot study on patient reporting through patient
      associations].
AB  - BACKGROUND: The expected evolution of monitoring systems for health products,
      aims at increasing the involvement of patients into health products safety
      system. As a result, it seems necessary to consider the ability for patients to
      directly report their own adverse events. METHODS: A pilot study has been
      undertaken by Afssaps (Health Agency) for 23 patient associations using a
      reporting form specially created for patients. RESULTS: According to the analysis
      of the first 200 reports, received from June 2006 to August 2007, the reported
      adverse events are mostly serious in terms of consequences on patients' quality
      of life and expected. The quality of information shows that the proposed tools
      are adequate and could be used in case of a future change in legislation allowing
      patient reporting of adverse events. CONCLUSION: The patient, eventually helped
      by his association, may provide contributory safety information, especially
      regarding side effects affecting daily life.

PMID- 19154709
TI  - [Factors of therapeutic imbalance of antivitamins K and their haemorrhagic
      consequences in elderly].
AB  - Objective. To determinate, for older subjects, specific factors of imbalance of
      the oral anticoagulant treatments. Method. We conducted an epidemiological and
      analytical case-control study, during 18 months, in 2 geriatrics centers. Each
      patient with excessive anticoagulation (INR>4.5) was matched with 2 controls
      under anticoagulant, whom the INR (international normalized ratio) had stayed in
      the therapeutic range. Results. One-hundred fifty nine subjects (53 cases and 106
      controls) were included. Haemorrhagic complications has been observed in 19.2% of
      cases, versus 3.9% of the controls. Some medicines frequently prescribed to the
      old subjects were correlated at a risk of excessive anticoagulation: amiodarone
      (9.4% versus 0, p<0.004), acetaminophen (18.9% versus 0.9%, p<0.001), tramadol
      (5.6% versus 0, p<0.04), ofloxacine (11.3% versus 1.9%, p<0.001), and lactulose
      (11.3% versus 0, p<0.001). Furthermore, several acute states increase the risk of
      excessive INR to the old subjects: fever (p<0.001), malnutrition (p<0.001),
      dehydration (p=0.006), and acute diarrhea (p<0.001). Conclusion. Some specific
      geriatric factors raised may destabilize treatments by anticoagulants.

PMID- 19154710
TI  - Dystroglycan and AMP kinase: polarity's protectors when the power goes out.
AB  - The AMP-stimulated protein kinase regulates epithelial polarity under conditions
      of energy depletion by phosphorylating the myosin regulatory light chain. In this
      issue of Developmental Cell, Mirouse et al. demonstrate that dystroglycan and
      perlecan, an extracellular matrix receptor and its ligand, help localize myosin
      regulatory light chain, making it available for phosphorylation by AMP kinase in
      response to energy stress.

PMID- 19154711
TI  - A Tf-independent iron transport system required for organogenesis.
AB  - Cells require iron as a cofactor for proteins that are essential for growth.
      While delivery of iron to cells by transferrin is well known, Li et al. in this
      issue of Developmental Cell show that ferritin, through its binding to the cell
      surface Scara5 receptor, can also deliver iron to cells, permitting kidney
      organogenesis.

PMID- 19154712
TI  - Chaos begets order: asynchronous cell contractions drive epithelial
      morphogenesis.
AB  - Apical cell contraction triggers tissue folding and invagination in epithelia.
      During Drosophila gastrulation, ventral furrow formation was thought to be driven
      by smooth, purse-string-like constriction of an acto-myosin belt underlying
      adherens junctions. Now Martin et al. report in Nature that ventral furrow
      formation is triggered by asynchronous pulsed contractions of the apical acto
      myosin cortex in individual cells.

PMID- 19154713
TI  - Relaying the checkpoint signal from kinetochore to APC/C.
AB  - The mitotic checkpoint delays chromosome segregation until the last chromosome
      has correctly attached to the spindle. Exactly how this unattached chromosome can
      generate a checkpoint signal and inhibit the anaphase promoting complex/cyclosome
      (APC/C) is unknown. Two Developmental Cell papers in this issue by Kulukian et
      al. and Malureanu et al. now provide insight into how checkpoint components Mad2
      and BubR1 relay the checkpoint signal from kinetochores to APC/C.

PMID- 19154714
TI  - 3D chromatin regulation of Sonic hedgehog in the limb buds.
AB  - Understanding the mechanisms that regulate gene expression during development is
      a major challenge in science. In this issue of Developmental Cell, Amano and
      colleagues report that expression of Sonic hedgehog (Shh) protein in the
      posterior mesenchyme of the mouse limb bud correlates with a long-range chromatin
      interaction with enhancer MFCS1 and looping of the Shh locus from its chromosome
      territory (CT).

PMID- 19154715
TI  - Great expectations for PIP: phosphoinositides as regulators of signaling during
      development and disease.
AB  - Phosphoinositides function as signaling precursors as well as regulators and
      scaffolds of signaling molecules required for important cellular processes such
      as membrane trafficking. Although a picture of the biochemical and cell
      biological functions of phosphoinositides is emerging, less is known about how
      these functions impact signaling on a broader scale during development. This
      review summarizes recent work on the role of phosphoinositides in developmental
      signaling and in a number of diseases and developmental disorders.

PMID- 19154716
TI  - The Jekyll and Hyde functions of caspases.
AB  - Apoptosis is an ancient form of regulated cell death that functions under
      pathological and nonpathological contexts in all metazoans. More than a decade of
      intense research has led to extensive characterization of the core molecular
      mechanisms for apoptotic cell death. This includes the identification of a family
      of cysteine proteases, caspases, which are critical for the execution of
      apoptosis. Whereas completion of the proteolytic caspase cascade leads to
      elimination of a cell by apoptosis, caspase activation, when finely tuned,
      directs alternative cellular functions independent of cell death. Exciting recent
      developments have focused on uncovering nonapoptotic roles of caspases ranging
      from immune regulation to spermatogenesis, in highly specialized cellular
      frameworks.

PMID- 19154717
TI  - Scara5 is a ferritin receptor mediating non-transferrin iron delivery.
AB  - Developing organs require iron for a myriad of functions, but embryos deleted of
      the major adult transport proteins, transferrin or its receptor transferrin
      receptor1 (TfR1(-/-)), still initiate organogenesis, suggesting that non
      transferrin pathways are important. To examine these pathways, we developed
      chimeras composed of fluorescence-tagged TfR1(-/-) cells and untagged wild-type
      cells. In the kidney, TfR1(-/-) cells populated capsule and stroma, mesenchyme
      and nephron, but were underrepresented in ureteric bud tips. Consistently, TfR1
      provided transferrin to the ureteric bud, but not to the capsule or the stroma.
      Instead of transferrin, we found that the capsule internalized ferritin. Since
      the capsule expressed a novel receptor called Scara5, we tested its role in
      ferritin uptake and found that Scara5 bound serum ferritin and then stimulated
      its endocytosis from the cell surface with consequent iron delivery. These data
      implicate cell type-specific mechanisms of iron traffic in organogenesis, which
      alternatively utilize transferrin or non-transferrin iron delivery pathways.

PMID- 19154719
TI  - Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density
      in angiogenesis.
AB  - When and where to make or break new blood vessel connections is the key to
      understanding guided vascular patterning. VEGF-A stimulation and Dll4/Notch
      signaling cooperatively control the number of new connections by regulating
      endothelial tip cell formation. Here, we show that the Notch-regulated ankyrin
      repeat protein (Nrarp) acts as a molecular link between Notch- and Lef1-dependent
      Wnt signaling in endothelial cells to control stability of new vessel connections
      in mouse and zebrafish. Dll4/Notch-induced expression of Nrarp limits Notch
      signaling and promotes Wnt/Ctnnb1 signaling in endothelial stalk cells through
      interactions with Lef1. BATgal-reporter expression confirms Wnt signaling
      activity in endothelial stalk cells. Ex vivo, combined Wnt3a and Dll4 stimulation
      of endothelial cells enhances Wnt-reporter activity, which is abrogated by loss
      of Nrarp. In vivo, loss of Nrarp, Lef1, or endothelial Ctnnb1 causes vessel
      regression. We suggest that the balance between Notch and Wnt signaling
      determines whether to make or break new vessel connections.

PMID- 19154718
TI  - Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining
      pillar cell fate in the organ of Corti.
AB  - The organ of Corti, the auditory organ of the inner ear, contains two types of
      sensory hair cells and at least seven types of supporting cells. Most of these
      supporting cell types rely on Notch-dependent expression of Hes/Hey transcription
      factors to maintain the supporting cell fate. Here, we show that Notch signaling
      is not necessary for the differentiation and maintenance of pillar cell fate,
      that pillar cells are distinguished by Hey2 expression, and that-unlike other
      Hes/Hey factors-Hey2 expression is Notch independent. Hey2 is activated by FGF
      and blocks hair cell differentiation, whereas mutation of Hey2 leaves pillar
      cells sensitive to the loss of Notch signaling and allows them to differentiate
      as hair cells. We speculate that co-option of FGF signaling to render Hey2 Notch
      independent also liberated pillar cells from the need for direct contact with
      surrounding hair cells, and enabled evolutionary remodeling of the complex
      cellular mosaic of the inner ear.

PMID- 19154720
TI  - Dystroglycan and perlecan provide a basal cue required for epithelial polarity
      during energetic stress.
AB  - Dystroglycan localizes to the basal domain of epithelial cells and has been
      reported to play a role in apical-basal polarity. Here, we show that Dystroglycan
      null mutant follicle cells have normal apical-basal polarity, but lose the planar
      polarity of their basal actin stress fibers, a phenotype it shares with
      Dystrophin mutants. However, unlike Dystrophin mutants, mutants in Dystroglycan
      or in its extracellular matrix ligand Perlecan lose polarity under energetic
      stress. The maintenance of epithelial polarity under energetic stress requires
      the activation of Myosin II by the cellular energy sensor AMPK. Starved
      Dystroglycan or Perlecan null cells activate AMPK normally, but do not activate
      Myosin II. Thus, Perlecan signaling through Dystroglycan may determine where
      Myosin II can be activated by AMPK, thereby providing the basal polarity cue for
      the low-energy epithelial polarity pathway. Since Dystroglycan is often
      downregulated in tumors, loss of this pathway may play a role in cancer
      progression.

PMID- 19154721
TI  - Plasma membrane polarity and compartmentalization are established before
      cellularization in the fly embryo.
AB  - Patterning in the Drosophila embryo requires local activation and dynamics of
      proteins in the plasma membrane (PM). We used in vivo fluorescence imaging to
      characterize the organization and diffusional properties of the PM in the early
      embryonic syncytium. Before cellularization, the PM is polarized into discrete
      domains having epithelial-like characteristics. One domain resides above
      individual nuclei and has apical-like characteristics, while the other domain is
      lateral to nuclei and contains markers associated with basolateral membranes and
      junctions. Pulse-chase photoconversion experiments show that molecules can
      diffuse within each domain but do not exchange between PM regions above adjacent
      nuclei. Drug-induced F-actin depolymerization disrupted both the apicobasal-like
      polarity and the diffusion barriers within the syncytial PM. These events
      correlated with perturbations in the spatial pattern of dorsoventral Toll
      signaling. We propose that epithelial-like properties and an intact F-actin
      network compartmentalize the PM and shape morphogen gradients in the syncytial
      embryo.

PMID- 19154722
TI  - Unattached kinetochores catalyze production of an anaphase inhibitor that
      requires a Mad2 template to prime Cdc20 for BubR1 binding.
AB  - Premature anaphase onset is prevented by the mitotic checkpoint through
      production of a "wait anaphase" inhibitor(s) that blocks recognition of cyclin B
      and securin by Cdc20-activated APC/C, an E3 ubiquitin ligase that targets them
      for destruction. Using physiologically relevant levels of Mad2, Bub3, BubR1, and
      Cdc20, we demonstrate that unattached kinetochores on purified chromosomes
      catalytically generate a diffusible Cdc20 inhibitor or inhibit Cdc20 already
      bound to APC/C. Furthermore, the chromosome-produced inhibitor requires both
      recruitment of Mad2 by Mad1 that is stably bound at unattached kinetochores and
      dimerization-competent Mad2. We show that purified chromosomes promote BubR1
      binding to APC/C-Cdc20 by acting directly on Mad2, but not BubR1. Our results
      support a model in which immobilized Mad1/Mad2 at kinetochores provides a
      template for initial assembly of Mad2 bound to Cdc20 that is then converted to a
      final mitotic checkpoint inhibitor with Cdc20 bound to BubR1.

PMID- 19154723
TI  - BubR1 N terminus acts as a soluble inhibitor of cyclin B degradation by
      APC/C(Cdc20) in interphase.
AB  - BubR1 is an essential mitotic checkpoint protein with multiple functional
      domains. It has been implicated in mitotic checkpoint control, as an active
      kinase at unattached kinetochores, and as a cytosolic inhibitor of APC/C(Cdc20)
      activity, as well as in mitotic timing and stable chromosome-spindle attachment.
      Using BubR1-conditional knockout cells and BubR1 domain mutants, we demonstrate
      that the N-terminal Cdc20 binding domain of BubR1 is essential for all of these
      functions, whereas its C-terminal Cdc20-binding domain, Bub3-binding domain, and
      kinase domain are not. We find that the BubR1 N terminus binds to Cdc20 in a KEN
      box-dependent manner to inhibit APC/C activity in interphase, thereby allowing
      accumulation of cyclin B in G(2) phase prior to mitosis onset. Together, our
      results suggest that kinetochore-bound BubR1 is nonessential and that soluble
      BubR1 functions as a pseudosubstrate inhibitor of APC/C(Cdc20) during interphase
      to prevent unscheduled degradation of specific APC/C substrates.

PMID- 19154724
TI  - Cell polarity determinants establish asymmetry in MEN signaling.
AB  - Components of the mitotic exit network (MEN), a signaling pathway that triggers
      exit from mitosis, localize to the spindle pole body (SPB) that migrates into the
      daughter cell during anaphase but are largely absent from the SPB that remains in
      the mother cell. Through the analysis of one of the determinants of this
      asymmetry, Bfa1, we find that the machinery responsible for establishing cell
      polarity and cytoplasmic microtubules collaborate to establish MEN asymmetry. In
      cells defective in the Cdc42 signaling pathway or the formin Bni1, Bfa1 localizes
      to both SPBs. The quantitative analysis of Bfa1 localization further shows that
      Bfa1 can associate with both SPBs in a transient and highly dynamic fashion, but
      the protein is stabilized on the SPB that migrates into the daughter cell during
      anaphase through microtubule-bud cortex interactions. Our results indicate that
      mother-daughter cell asymmetry determinants establish MEN signaling asymmetry
      through microtubule-bud cortex interactions.

PMID- 19154725
TI  - Spindle alignment regulates the dynamic association of checkpoint proteins with
      yeast spindle pole bodies.
AB  - In many polarized cells, the accuracy of chromosome segregation depends on the
      correct positioning of the mitotic spindle. In budding yeast, the spindle
      positioning checkpoint (SPOC) delays mitotic exit when the anaphase spindle fails
      to extend toward the mother-daughter axis. However it remains to be established
      how spindle orientation is translated to SPOC components at the yeast spindle
      pole bodies (SPB). Here, we used photobleaching techniques to show that the
      dynamics with which Bub2-Bfa1 turned over at SPBs significantly increased upon
      SPOC activation. A version of Bfa1 that was stably associated with SPBs rendered
      the cells SPOC deficient without affecting other Bub2-Bfa1 functions,
      demonstrating the functional importance of regulating the dynamics of Bfa1 SPB
      association. In addition, we established that the SPOC kinase Kin4 is the major
      regulator of Bfa1 residence time at SPBs. We suggest that upon SPOC activation
      Bfa1-Bub2 spreads throughout the cytoplasm, thereby inhibiting mitotic exit.

PMID- 19154726
TI  - Global kinetic explorer: a new computer program for dynamic simulation and
      fitting of kinetic data.
AB  - We describe a new dynamic kinetic simulation program that allows multiple data
      sets to be fit simultaneously to a single model based on numerical integration of
      the rate equations describing the reaction mechanism. Unlike other programs that
      allow fitting based on numerical integration of rate equations, in the dynamic
      simulation rate constants, output factors, and starting concentrations of
      reactants can be scrolled while observing the change in the shape of the
      simulated reaction curves. Fast dynamic simulation facilitates the exploration of
      initial parameters that serve as the starting point for nonlinear regression in
      fitting data and facilitates exploration of the relationships between individual
      constants and observable reactions. The exploration of parameter space by dynamic
      simulation provides a powerful tool for learning kinetics and for evaluating the
      extent to which parameters are constrained by the data. This feature is critical
      to avoid overly complex models that are not supported by the data.

PMID- 19154727
TI  - Flash chronopotentiometric sensing of the polyions protamine and heparin at ion
      selective membranes.
AB  - We report here on a highly sensitive and rapid detection technique, multipulse
      flash chronopotentiometry, for the anticoagulant polyion heparin and its antidote
      protamine. The technique is based on a localized titration of the polyions at the
      surface of an appropriately formulated polymeric ion-selective membrane devoid of
      ion exchange properties to prohibit spontaneous extraction processes. A defined
      ion flux from the sample side to the membrane is induced electrochemically by
      applying a current pulse of appropriate amplitude and sign. The resulting
      depletion of the measured ions at the membrane surface gives rise to a
      characteristic limiting current or transition time and is observed as an
      inflection point in the resulting chronopotentiogram. The limiting current and
      the square root of the transition time are linear functions of the concentration
      of the polyion and yield sensitive and rapid analytical information attractive
      for clinical diagnostics applications. The polyion protamine is detected in 10
      fold diluted blood samples in a matter of seconds via a cathodic current pulse.
      The utility of the technique for monitoring heparin/protamine titrations in
      physiological saline solutions is demonstrated.

PMID- 19154728
TI  - Everolimus and sirolimus antagonize tacrolimus based calcineurin inhibition via
      competition for FK-binding protein 12.
AB  - The calcineurin inhibitors cyclosporin A and tacrolimus and the inhibitors of the
      mTOR, sirolimus and everolimus bind immunophilins that are required for their
      immunosuppressive action. In contrast to cyclosporin A, tacrolimus and the mTOR
      inhibitors (MTIs) share common immunophilins, the FK506-binding proteins (FKBPs).
      We investigated the immunosuppressive interactions of MTIs on tacrolimus based
      immune suppression, since insights in immunological drug-drug interactions can be
      very relevant for optimization of immunosuppressive regimens in allograft
      transplantation medicine. Isolated peripheral blood mononuclear cells from
      healthy volunteers were incubated with combinations of MTIs and calcineurin
      inhibitors and when monitored for calcineurin activity and IL-2 excretion after
      mitogen stimulation, tacrolimus IC(50) concentrations shifted to higher
      concentrations in the presence of MTIs. This antagonism was absent for
      cyclosporin A, reproducible for 10 healthy volunteers (p<0.001) and stronger for
      sirolimus than for everolimus. When cell lysate was treated with and without MTI,
      tacrolimus and FKBP12, FKBP12 could increase calcineurin inhibition by tacrolimus
      and reverse the MTI antagonism for both MTIs. These results demonstrate that
      FKBP12 can be rate limiting for calcineurin inhibition at high tacrolimus
      concentrations and that the antagonism of sirolimus and everolimus on tacrolimus
      based immune suppression is mediated via saturation of FKBP12.

PMID- 19154730
TI  - Plasma advanced glycation endproduct, methylglyoxal-derived hydroimidazolone is
      elevated in young, complication-free patients with Type 1 diabetes.
AB  - OBJECTIVES: Elevated advanced glycation endproducts (AGEs) are implicated in
      diabetic complications. Methylglyoxal-derived hydroimidazolone (MG-H) is one of
      the most abundant AGEs in vivo. Our objective was to develop a time-saving,
      specific method to measure free MG-H in plasma and determine its levels in
      complication-free young individuals with Type 1 diabetes (T1DM). The relationship
      of plasma free MG-H to hemoglobin A1C (A1C) and plasma methylglyoxal levels was
      also determined. DESIGN AND METHODS: A solid phase extraction and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, and free
      plasma MG-H levels were measured in 40 T1DM patients (DM group), aged 6-21 years,
      and 11 non-diabetics (ND group), 6-22 years. Methylglyoxal was measured using LC
      MS/MS and A1C by a Tosoh G7 high-performance liquid chromatograph. RESULTS: Our
      method showed high recovery, sensitivity and short run-time. Plasma free MG-H
      (nmol/L) was higher (p<0.001) in the DM group (1318+/-569; mean+/-standard
      deviation) as compared to the ND group (583+/-419). Within the DM group, plasma
      free MG-H did not correlate with plasma methylglyoxal or A1C. CONCLUSIONS: Our LC
      MS/MS method to measure free MG-H in plasma may be useful for future clinical
      application. The increased levels of free MG-H observed in individuals with TIDM
      are not merely the result of short term changes in glucose or methylglyoxal, but
      may reflect long-term alterations to tissue proteins.

PMID- 19154729
TI  - Nitric oxide inhibits insulin-degrading enzyme activity and function through S
      nitrosylation.
AB  - Insulin-degrading enzyme (IDE) is responsible for the degradation of a number of
      hormones and peptides, including insulin and amyloid beta (Abeta). Genetic
      studies have linked IDE to both type 2 diabetes and Alzheimer's disease. Despite
      its potential importance in these diseases, relatively little is known about the
      factors that regulate the activity and function of IDE. Protein S-nitrosylation
      is now recognized as a redox-dependent, cGMP-independent signaling component that
      mediates a variety of actions of nitric oxide (NO). Here we describe a mechanism
      of inactivation of IDE by NO. NO donors decreased both insulin and Abeta
      degrading activities of IDE. Insulin-degrading activity appeared more sensitive
      to NO inhibition than Abeta degrading activity. IDE-mediated regulation of
      proteasome activity was affected similarly to insulin-degrading activity. We
      found IDE to be nitrosylated in the presence of NO donors compared to that of
      untreated enzyme and the control compound. S-nitrosylation of IDE enzyme did not
      affect the insulin degradation products produced by the enzyme, nor did NO affect
      insulin binding to IDE as determined by cross-linking studies. Kinetic analysis
      of NO inhibition of IDE confirmed that the inhibition was noncompetitive. These
      data suggest a possible reversible mechanism by which inhibition of IDE under
      conditions of nitrosative stress could contribute to pathological disease
      conditions such as Alzheimer's disease and type 2 diabetes.

PMID- 19154731
TI  - Thyroglobulin and anti-thyroglobulin assays in thyroid cancer monitoring.
AB  - OBJECTIVES: To compare four methods for thyroglobulin (Tg) quantitation and three
      methods for detection and quantitation of thyroglobulin antibodies (Tg-Ab). We
      also wanted to explore the premise that thyroglobulin antibodies, as determined
      by commercially available assays, interfere with thyroglobulin assays in a
      predictable way. METHODS: Split sample method comparisons were run on all the
      methods for both the thyroglobulin and anti-thyroglobulin assays. In addition to
      this, samples from patients that had disseminated thyroid cancer but had low
      serum thyroglobulin concentrations and high thyroglobulin antibodies were further
      studied. These studies involved doing recovery studies (or antibody inhibition
      studies). RESULTS: There was good agreement between methods for quantitation of
      thyroglobulin with slopes ranging from 0.77 to 1.23 although closer agreement was
      expected as the assays are all calibrated to the same reference standard (CRM
      457). The situation for the thyroglobulin antibody assays is significantly worse,
      and the rate of antibody positivity ranged from 9-21% in this group of patients
      although there was agreement in only 6%. Different reference standards are used
      for the Tg-Ab assays we investigated. The Tg-Ab data did not lend itself to
      traditional linear regression analysis as the data showed wide scatter.
      CONCLUSIONS: There is good agreement between the four thyroglobulin assays
      compared in this study. The linear regression analysis shows that there is
      proportional error present between the methods that is greater than 50%. This
      study is unable to demonstrate any difference in assay values based on the amount
      of anti-thyroglobulin present in the specimen. The agreement between different
      anti-thyroglobulin assays is very poor. This finding is very problematic since it
      makes it difficult to generalize any literature reports of interference. All the
      thyroglobulin assays appear to be suitable for monitoring patients with thyroid
      cancer, provided that the differences in calibration are taken into account.
      Differences in calibration between different assays need to be taken into account
      when changing assays. Conversely, the anti-thyroglobulin assays are virtually
      useless since there appears to be very little agreement between the three assays
      studied and no evidence of assay interference in the measurements of
      thyroglobulin.

PMID- 19154733
TI  - Why the embryo still matters: CSF and the neuroepithelium as interdependent
      regulators of embryonic brain growth, morphogenesis and histiogenesis.
AB  - The key focus of this review is that both the neuroepithelium and embryonic
      cerebrospinal fluid (CSF) work in an integrated way to promote embryonic brain
      growth, morphogenesis and histiogenesis. The CSF generates pressure and also
      contains many biologically powerful trophic factors; both play key roles in early
      brain development. Accumulation of fluid via an osmotic gradient creates pressure
      that promotes rapid expansion of the early brain in a developmental regulated
      way, since the rates of growth differ between the vesicles and for different
      species. The neuroepithelium and ventricles both contribute to this growth but by
      different and coordinated mechanisms. The neuroepithelium grows primarily by cell
      proliferation and at the same time the ventricle expands via hydrostatic pressure
      generated by active transport of Na(+) and transport or secretion of proteins and
      proteoglycans that create an osmotic gradient which contribute to the
      accumulation of fluid inside the sealed brain cavity. Recent evidence shows that
      the CSF regulates relevant aspects of neuroepithelial behavior such as cell
      survival, replication and neurogenesis by means of growth factors and morphogens.
      Here we try to highlight that early brain development requires the coordinated
      interplay of the CSF contained in the brain cavity with the surrounding
      neuroepithelium. The information presented is essential in order to understand
      the earliest phases of brain development and also how neuronal precursor behavior
      is regulated.

PMID- 19154732
TI  - Wnt and EGF pathways act together to induce C. elegans male hook development.
AB  - Comparative studies of vulva development between Caenorhabditis elegans and other
      nematode species have provided some insight into the evolution of patterning
      networks. However, molecular genetic details are available only in C. elegans and
      Pristionchus pacificus. To extend our knowledge on the evolution of patterning
      networks, we studied the C. elegans male hook competence group (HCG), an
      equivalence group that has similar developmental origins to the vulval precursor
      cells (VPCs), which generate the vulva in the hermaphrodite. Similar to VPC fate
      specification, each HCG cell adopts one of three fates (1 degree, 2 degrees, 3
      degrees), and 2 degrees HCG fate specification is mediated by LIN-12/Notch. We
      show that 2 degrees HCG specification depends on the presence of a cell with the
      1 degree fate. We also provide evidence that Wnt signaling via the Frizzled-like
      Wnt receptor LIN-17 acts to specify the 1 degree and 2 degrees HCG fate. A
      requirement for EGF signaling during 1 degree fate specification is seen only
      when LIN-17 activity is compromised. In addition, activation of the EGF pathway
      decreases dependence on LIN-17 and causes ectopic hook development. Our results
      suggest that WNT plays a more significant role than EGF signaling in specifying
      HCG fates, whereas in VPC specification EGF signaling is the major inductive
      signal. Nonetheless, the overall logic is similar in the VPCs and the HCG: EGF
      and/or WNT induce a 1 degree lineage, and LIN-12/NOTCH induces a 2 degrees
      lineage. Wnt signaling is also required for execution of the 1 degree and 2
      degrees HCG lineages. lin-17 and bar-1/beta-catenin are preferentially expressed
      in the presumptive 1 degree cell P11.p. The dynamic subcellular localization of
      BAR-1-GFP in P11.p is concordant with the timing of HCG fate determination.

PMID- 19154735
TI  - Use of novel devices for control of intraocular pressure.
AB  - This brief review in honor of Douglas Johnson, MD describes the rationales and
      initial clinical outcomes in studies to date on Trabectome, Glaukos iStent,
      iScience (canaloplasty), and Solx (suprachoroidal shunt), all newly developed
      surgical technologies for treatment of open-angle glaucomas. These new approaches
      to angle surgery have been demonstrated in preliminary case series to safely
      lower IOP in the mid-teens with far fewer complications than expected with
      trabeculectomy and without anti-fibrotics. Trabectome and iStent are relatively
      non-invasive, aim to improve access of aqueous to collector channels and do not
      preclude subsequent standard surgery. Canaloplasty, modified from
      viscocanalostomy, is thought to improve trans-trabecular flow. Solx potentially
      offers an adjustable aqueous outflow into the suprachoroidal space.

PMID- 19154734
TI  - Explanation for excessive DNA single-strand breaks and endogenous repair foci in
      pluripotent mouse embryonic stem cells.
AB  - Pluripotent mouse embryonic stem cells (mES cells) exhibit approximately 100
      large gammaH2AX repair foci in the absence of measurable numbers of DNA double
      strand breaks. Many of these cells also show excessive numbers of DNA single
      strand breaks (>10,000 per cell) when analyzed using the alkaline comet assay. To
      understand the reasons for these unexpected observations, various methods for
      detecting DNA strand breaks were applied to wild-type mES cells and to mES cells
      lacking H2AX, ATM, or DNA-PKcs. H2AX phosphorylation and expression of other
      repair complexes were measured using flow and image analysis of antibody-stained
      cells. Results indicate that high numbers of endogenous gammaH2AX foci and single
      strand breaks in pluripotent mES cells do not require ATM or DNA-PK kinase
      activity and appear to be associated with global chromatin decondensation rather
      than pre-existing DNA damage. This will limit applications of gammaH2AX foci
      analysis in mES cells to relatively high levels of initial or residual DNA
      damage. Excessive numbers of single-strand breaks in the alkaline comet assay can
      be explained by the vulnerability of replicating chromatin in mES cells to
      osmotic shock. This suggests that caution is needed in interpreting results with
      the alkaline comet assay when applied to certain cell types or after treatment
      with agents that make chromatin vulnerable to osmotic changes. Differentiation of
      mES cells caused a reduction in histone acetylation, gammaH2AX foci intensity,
      and DNA single-strand breakage, providing a link between chromatin structural
      organization, excessive gammaH2AX foci, and sensitivity of replicating mES cell
      chromatin to osmotic shock.

PMID- 19154736
TI  - Structural rearrangements linked to global folding pathways of the Azoarcus group
      I ribozyme.
AB  - Stable RNAs must fold into specific three-dimensional structures to be
      biologically active, yet many RNAs form metastable structures that compete with
      the native state. Our previous time-resolved footprinting experiments showed that
      Azoarcus group I ribozyme forms its tertiary structure rapidly (tau < 30 ms)
      without becoming significantly trapped in kinetic intermediates. Here, we use
      stopped-flow fluorescence spectroscopy to probe the global folding kinetics of a
      ribozyme containing 2-aminopurine in the loop of P9. The modified ribozyme was
      catalytically active and exhibited two equilibrium folding transitions centered
      at 0.3 and 1.6 mM Mg2+, consistent with previous results. Stopped-flow
      fluorescence revealed four kinetic folding transitions with observed rate
      constants of 100, 34, 1, and 0.1 s-1 at 37 degrees C. From comparison with time
      resolved Fe(II)-ethylenediaminetetraacetic acid footprinting of the modified
      ribozyme under the same conditions, these folding transitions were assigned to
      formation of the IC intermediate, tertiary folding and docking of the nicked P9
      tetraloop, reorganization of the P3 pseudoknot, and refolding of nonnative
      conformers, respectively. The footprinting results show that 50-60% of the
      modified ribozyme folds in less than 30 ms, while the rest of the RNA population
      undergoes slow structural rearrangements that control the global folding rate.
      The results show how small perturbations to the structure of the RNA, such as a
      nick in P9, populate kinetic folding intermediates that are not observed in the
      natural ribozyme.

PMID- 19154737
TI  - HIV-1 nucleocapsid protein switches the pathway of transactivation response
      element RNA/DNA annealing from loop-loop "kissing" to "zipper".
AB  - The chaperone activity of HIV-1 (human immunodeficiency virus type 1)
      nucleocapsid protein (NC) facilitates multiple nucleic acid rearrangements that
      are critical for reverse transcription of the single-stranded RNA genome into
      double-stranded DNA. Annealing of the transactivation response element (TAR) RNA
      hairpin to a complementary TAR DNA hairpin is an essential step in the minus
      strand transfer step of reverse transcription. Previously, we used truncated 27
      nt mini-TAR RNA and DNA constructs to investigate this annealing reaction pathway
      in the presence and in the absence of HIV-1 NC. In this work, full-length 59-nt
      TAR RNA and TAR DNA constructs were used to systematically study TAR hairpin
      annealing kinetics. In the absence of NC, full-length TAR hairpin annealing is
      approximately 10-fold slower than mini-TAR annealing. Similar to mini-TAR
      annealing, the reaction pathway for TAR in the absence of NC involves the fast
      formation of an unstable "kissing" loop intermediate, followed by a slower
      conversion to an extended duplex. NC facilitates the annealing of TAR by
      approximately 10(5)-fold by stabilizing the bimolecular intermediate (
      approximately 10(4)-fold) and promoting the subsequent exchange reaction (
      approximately 10-fold). In contrast to the mini-TAR annealing pathway, wherein NC
      mediated annealing can initiate through both loop-loop kissing and a distinct
      "zipper" pathway involving nucleation at the 3'-/5'-terminal ends, full-length
      TAR hairpin annealing switches predominantly to the zipper pathway in the
      presence of saturated NC.

PMID- 19154738
TI  - The identification of the determinants of the cyclic, sequential binding of
      elongation factors tu and g to the ribosome.
AB  - Experiments dedicated to gaining an understanding of the mechanism underlying the
      orderly, sequential association of elongation factor Tu (EF-Tu) and elongation
      factor G (EF-G) with the ribosome during protein synthesis were undertaken. The
      binding of one EF is always followed by the binding of the other, despite the two
      sharing the same-or a largely overlapping-site and despite the two having
      isosteric structures. Aminoacyl-tRNA, peptidyl-tRNA, and deacylated-tRNA were
      bound in various combinations to the A-site, P-site, or E-site of ribosomes, and
      their effect on conformation in the peptidyl transferase center, the GTPase
      associated center, and the sarcin/ricin domain (SRD) was determined. In addition,
      the effect of the ribosome complexes on sensitivity to the ribotoxins sarcin and
      pokeweed antiviral protein and on the binding of EF-G*GTP were assessed. The
      results support the following conclusions: the EF-Tu ternary complex binds to the
      A-site whenever it is vacant and the P-site has peptidyl-tRNA; and association of
      the EF-Tu ternary complex is prevented, simply by steric hindrance, when the A
      site is occupied by peptidyl-tRNA. On the other hand, the affinity of the
      ribosome for EF-G*GTP is increased when peptidyl-tRNA is in the A-site, and the
      increase is the result of a conformational change in the SRD. We propose that
      peptidyl-tRNA in the A-site is an effector that initiates a series of changes in
      tertiary interactions between nucleotides in the peptidyl transferase center, the
      SRD, and the GTPase-associated center of 23S rRNA; and that the signal,
      transmitted through a transduction pathway, informs the ribosome of the position
      of peptidyl-tRNA and leads to a conformational change in the SRD that favors
      binding of EF-G.

PMID- 19154739
TI  - Thermodynamic and kinetic characterization of a germ line human lambda6 light
      chain protein: the relation between unfolding and fibrillogenesis.
AB  - Proteins encoded by the gene segment 6a of the lambda variable light-chain
      repertoire are strongly associated with amyloid deposition. 6aJL2 is a model
      protein constructed with the predicted sequences encoded by the 6a and JL2 germ
      line genes. In this work, we characterized the urea- and temperature-induced
      unfolding of 6aJL2. In the short time scale, spectroscopic, hydrodynamic and
      calorimetric experiments were compatible with a two-state transition.
      Furthermore, DeltaG, m and the midpoint urea concentration obtained from
      equilibrium experiments were compatible with those obtained from kinetic
      experiments. Since fibril formation is a slow process, samples were also
      incubated for longer times. After incubation for several hours at 37 degrees C,
      spectroscopic, hydrodynamic and calorimetric experiments revealed the presence of
      a partially unfolded off-pathway intermediate around the midpoint urea
      concentration (1.5-3.0 M urea). In vitro fibrillogenesis assays show that the
      maximum growth rate for fibril formation and the minimum lag time were obtained
      at urea concentrations where the partially unfolded state was populated (2.5 M
      urea at 37 degrees C). This indicates that this partially unfolded state is
      critical for in vitro fibril formation. Concentration-dependent kinetics and
      hydrodynamic properties of the intermediate were consistent with a soluble
      oligomeric state. The intermediate is formed around the midpoint urea
      concentration, where the native and unfolded states are equally populated and
      their rate of interconversion is the slowest. This situation may promote the slow
      accumulation of an intermediate state that is prone to aggregate.

PMID- 19154741
TI  - SPRY domain-containing SOCS box protein 2: crystal structure and residues
      critical for protein binding.
AB  - The four mammalian SPRY (a sequence repeat in dual-specificity kinase splA and
      ryanodine receptors) domain-containing suppressor of cytokine signalling (SOCS)
      box proteins (SSB-1 to -4) are characterised by a C-terminal SOCS box and a
      central SPRY domain. The latter is a protein interaction module found in over
      1600 proteins, with more than 70 encoded in the human genome. Here we report the
      crystal structure of the SPRY domain of murine SSB-2 and compare it with the SSB
      2 solution structure and crystal structures of other B30.2/SPRY domain-containing
      family proteins. The structure is a bent beta-sandwich, consisting of two seven
      stranded beta-sheets wrapped around a long loop that extends from the centre
      strands of the inner or concave beta-sheet; it closely matches those of GUSTAVUS
      and SSB-4. The structure is also similar to those of two recently determined
      Neuralized homology repeat (NHR) domains (also known as NEUZ domains), with
      detailed comparisons, suggesting that the NEUZ/NHR domains form a subclass of
      SPRY domains. The binding site on SSB-2 for the prostate apoptosis response-4
      (Par-4) protein has been mapped in finer detail using mutational analyses.
      Moreover, SSB-1 was shown to have a Par-4 binding surface similar to that
      identified for SSB-2. Structural perturbations of SSB-2 induced by mutations
      affecting its interaction with Par-4 and/or c-Met have been characterised by NMR.
      These comparisons, in conjunction with previously published dynamics data from
      NMR relaxation studies and coarse-grained dynamics simulation using normal mode
      analysis, further refine our understanding of the structural basis for protein
      recognition of SPRY domain-containing proteins.

PMID- 19154740
TI  - Effect of Mg(2+) and Na(+) on the nucleic acid chaperone activity of HIV-1
      nucleocapsid protein: implications for reverse transcription.
AB  - The human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein (NC) is an
      essential protein for retroviral replication. Among its numerous functions, NC is
      a nucleic acid (NA) chaperone protein that catalyzes NA rearrangements leading to
      the formation of thermodynamically more stable conformations. In vitro, NC
      chaperone activity is typically assayed under conditions of low or no Mg(2+),
      even though reverse transcription requires the presence of divalent cations.
      Here, the chaperone activity of HIV-1 NC was studied as a function of varying
      Na(+) and Mg(2+) concentrations by investigating the annealing of complementary
      DNA and RNA hairpins derived from the trans-activation response domain of the HIV
      genome. This reaction mimics the annealing step of the minus-strand transfer
      process in reverse transcription. Gel-shift annealing and sedimentation assays
      were used to monitor the annealing kinetics and aggregation activity of NC,
      respectively. In the absence of protein, a limited ability of Na(+) and Mg(2+)
      cations to facilitate hairpin annealing was observed, whereas NC stimulated the
      annealing 10(3)- to 10(5)-fold. The major effect of either NC or the cations is
      on the rate of bimolecular association of the hairpins. This effect is especially
      strong under conditions wherein NC induces NA aggregation. Titration with NC and
      NC/Mg(2+) competition studies showed that the annealing kinetics depends only on
      the level of NA saturation with NC. NC competes with Mg(2+) or Na(+) for sequence
      nonspecific NA binding similar to a simple trivalent cation. Upon saturation, NC
      induces attraction between NA molecules corresponding to approximately 0.3
      kcal/mol/nucleotide, in agreement with an electrostatic mechanism of NC-induced
      NA aggregation. These data provide insights into the variable effects of NC's
      chaperone activity observed during in vitro studies of divalent metal-dependent
      reverse transcription reactions and suggest the feasibility of NC-facilitated
      proviral DNA synthesis within the mature capsid core.

PMID- 19154743
TI  - Nucleotide-induced flexibility change in neck linkers of dimeric kinesin as
      detected by distance Measurements using spin-labeling EPR.
AB  - Using dipolar continuous-wave and pulsed electron paramagnetic resonance methods,
      we have determined the distribution of the distances between two spin labels
      placed on the middle of each of the neck linkers of dimeric kinesin. In the
      absence of microtubules, the distance was centered at 3.3 nm, but displayed a
      broad distribution with a width of 2.7 nm. This broad distribution implies that
      the linkers are random coils and extend well beyond the 2.5-nm distance expected
      of crystal structures. In the presence of microtubules, two linker populations
      were found: one similar to that observed in the absence of microtubules (a broad
      distribution centered at 3.3 nm), and the second population with a narrower
      distribution centered at 1.3-2.5 nm. In the absence of nucleotide but in the
      presence of microtubules, approximately 40% of the linkers were at a distance
      centered at 1.9 nm with a 1.2-nm width; the remaining fraction was at 3.3 nm, as
      before. This suggests that neck linkers exhibit dynamics covering a wide distance
      range between 1.0 and 5.0 nm. In the presence of ATP analogs adenosine 5'
      (beta,gamma-imido)triphosphate and adenosine 5'-(gamma-thio)triphosphate, 40-50%
      of the spins showed a very narrow distribution centered at 1.6 nm, with a width
      of 0.4-0.5 nm. The remaining population displayed the broad 3.3-nm distribution.
      Under these conditions, a large fraction of linkers are docked firmly onto a
      motor core or microtubule, while the remainder is disordered. We propose that
      large nucleotide-dependent flexibility changes in the linkers contribute to the
      directional bias of the kinesin molecule stepping 8 nm along the microtubule.

PMID- 19154742
TI  - Predicting protein function and binding profile via matching of local
      evolutionary and geometric surface patterns.
AB  - Inferring protein functions from structures is a challenging task, as a large
      number of orphan protein structures from structural genomics project are now
      solved without their biochemical functions characterized. For proteins binding to
      similar substrates or ligands and carrying out similar functions, their binding
      surfaces are under similar physicochemical constraints, and hence the sets of
      allowed and forbidden residue substitutions are similar. However, it is difficult
      to isolate such selection pressure due to protein function from selection
      pressure due to protein folding, and evolutionary relationship reflected by
      global sequence and structure similarities between proteins is often unreliable
      for inferring protein function. We have developed a method, called pevoSOAR
      (pocket-based evolutionary search of amino acid residues), for predicting protein
      functions by solving the problem of uncovering amino acids residue substitution
      pattern due to protein function and separating it from amino acids substitution
      pattern due to protein folding. We incorporate evolutionary information specific
      to an individual binding region and match local surfaces on a large scale with
      millions of precomputed protein surfaces to identify those with similar
      functions. Our pevoSOAR method also generates a probablistic model called the
      computed binding a profile that characterizes protein-binding activities that may
      involve multiple substrates or ligands. We show that our method can be used to
      predict enzyme functions with accuracy. Our method can also assess enzyme binding
      specificity and promiscuity. In an objective large-scale test of 100 enzyme
      families with thousands of structures, our predictions are found to be sensitive
      and specific: At the stringent specificity level of 99.98%, we can correctly
      predict enzyme functions for 80.55% of the proteins. The overall area under the
      receiver operating characteristic curve measuring the performance of our
      prediction is 0.955, close to the perfect value of 1.00. The best Matthews
      coefficient is 86.6%. Our method also works well in predicting the biochemical
      functions of orphan proteins from structural genomics projects.

PMID- 19154744
TI  - Sequence-specific conformational dynamics of model transmembrane domains
      determines their membrane fusogenic function.
AB  - The transmembrane domains of fusion proteins are known to be functionally
      important and display an overabundance of helix-destabilizing Ile and Val
      residues. In an effort to systematically study the relationship of fusogenicity
      and helix stability, we previously designed LV peptides, a low-complexity model
      system whose hydrophobic core consists of Leu and Val residues at different
      ratios. The ability of LV peptides to fuse membranes increases with the content
      of helix-destabilizing residues. Here, we monitored the kinetics of amide
      deuterium/hydrogen exchange of LV-peptide helices to probe their conformational
      dynamics. The kinetics indeed increases strongly with the content of helix
      destabilizing residues and is likely to reflect local fluctuations of the helix
      backbones as all peptides exhibit uncorrelated exchange and contain
      subpopulations of amide deuterium atoms that exchange with different velocities.
      Interestingly, helices whose amide deuterium atoms are shifted from slower to
      faster subpopulations are more fusogenic. Novel peptide variants in which Val
      residues are concentrated at peripheral or central domains of the hydrophobic
      core were designed to map functionally relevant helix subdomains. Their
      structural and functional analysis suggests that dynamic domains close to the
      helix termini are more relevant for fusogenicity than central domains but
      cooperate with the latter to achieve strong fusogenicity.

PMID- 19154745
TI  - Mean-field modeling of the basal ganglia-thalamocortical system. II Dynamics of
      parkinsonian oscillations.
AB  - Neuronal correlates of Parkinson's disease (PD) include a shift to lower
      frequencies in the electroencephalogram (EEG) and enhanced synchronized
      oscillations at 3-7 and 7-30 Hz in the basal ganglia, thalamus, and cortex. This
      study describes the dynamics of a recent physiologically based mean-field model
      of the basal ganglia-thalamocortical system, and shows how it accounts for many
      key electrophysiological correlates of PD. Its detailed functional connectivity
      comprises partially segregated direct and indirect pathways through two
      populations of striatal neurons, a hyperdirect pathway involving a
      corticosubthalamic projection, thalamostriatal feedback, and local inhibition in
      striatum and external pallidum (GPe). In a companion paper, realistic steady
      state firing rates were obtained for the healthy state, and after dopamine loss
      modeled by weaker direct and stronger indirect pathways, reduced intrapallidal
      inhibition, lower firing thresholds of the GPe and subthalamic nucleus (STN), a
      stronger projection from striatum to GPe, and weaker cortical interactions. Here
      it is shown that oscillations around 5 and 20 Hz can arise with a strong indirect
      pathway, which also causes increased synchronization throughout the basal
      ganglia. Furthermore, increased theta power with progressive nigrostriatal
      degeneration is correlated with reduced alpha power and peak frequency, in
      agreement with empirical results. Unlike the hyperdirect pathway, the indirect
      pathway sustains oscillations with phase relationships that coincide with those
      found experimentally. Alterations in the responses of basal ganglia to transient
      stimuli accord with experimental observations. Reduced cortical gains due to both
      nigrostriatal and mesocortical dopamine loss lead to slower changes in cortical
      activity and may be related to bradykinesia. Finally, increased EEG power found
      in some studies may be partly explained by a lower effective GPe firing
      threshold, reduced GPe-GPe inhibition, and/or weaker intracortical connections in
      parkinsonian patients. Strict separation of the direct and indirect pathways is
      not necessary to obtain these results.

PMID- 19154746
TI  - Amiloride inhibits hydrogen peroxide-induced Ca2+ responses in human CNS
      pericytes.
AB  - The aims of the present study were to investigate the mechanisms of Ca(2+)
      signaling caused by hydrogen peroxide in CNS pericytes. In cultured human brain
      microvascular pericytes, cytosolic Ca(2+) concentration was measured by means of
      fura-2 fluorescence. Reverse transcription and polymerase chain reaction was
      performed to examine the expression of mRNA. Knockdown of Na(+)/H(+) exchanger
      (NHE) was done by transfecting the cells with specific double-strand siRNAs for
      NHE. Externally applied hydrogen peroxide dose-dependently (100 microM-10 mM)
      increased cytosolic Ca(2+) in human CNS pericytes. Cytosolic Ca(2+) remained high
      after wash-out of hydrogen peroxide. However, the addition of dithiothreitol
      rapidly reversed cytosolic Ca(2+) to the resting level. The hydrogen peroxide
      induced Ca(2+) increase was not inhibited by nicardipine, Gd(3+), La(3+), or
      omission of external Ca(2+). Neither thapsigargin nor carbonyl cyanide 4
      trifluoromethoxyphenylhydrazone attenuated the hydrogen peroxide-induced Ca(2+)
      rise. Amiloride and its derivatives, benzamil and hexamethylene amiloride
      reversed the hydrogen peroxide-induced Ca(2+) increase. Human CNS pericytes
      expressed acid sensing ion channel (ASIC) 1a, Na(+)/Ca(2+) exchanger (NCX) 1,
      Na(+)/H(+) exchanger (NHE) 1, and NHE7. However, the removal of external Na(+),
      treatment with KB-R 7943 and mibefradil, or knockdown of NHE1 and NHE7 did not
      affect the hydrogen peroxide-induced Ca(2+) increase. Hydrogen peroxide releases
      Ca(2+) from intracellular Ca(2+) pool via an amiloride-sensitive protein, which
      is controlled by oxidation of thiol group in human CNS pericytes.

PMID- 19154747
TI  - Parietal encoding of action in depth.
AB  - The posterior parietal cortex is a crucial node in the process of coordinates
      transformation for the visual control of eye and hand movements. This conviction
      stems from both neurophysiological studies in the behaving monkey and from the
      analysis of the consequences of parietal lobe lesions in humans. Despite an
      extensive literature concerning varying aspects of the composition and control of
      eye and hand movements, there is little information about the physiological
      processes responsible for encoding target distance and hand movement in depth or
      about their control and impairment in parietal patients. This review is an
      attempt to provide a comprehensive picture from the fragmentary material existing
      on this issue in the literature. This should serve as a basis for discussion of
      what we consider to be a prototypical function of the dorsal visuomotor stream in
      the primate brain, that of encoding eye and hand movement in depth.

PMID- 19154748
TI  - How do Korsakoff patients learn new concepts?
AB  - The goal of the present investigation was to assess semantic learning in
      Korsakoff patients (KS), compared with uncomplicated alcoholics (AL) and control
      subjects (CS), taking the nature of the information to-be-learned and the
      episodic memory profiles of the three groups into account. Ten new complex
      concepts, each illustrated by a photo and composed of a label, a category and
      three features, were taught to 13 KS, 23 AL and 45 CS. When examined
      independently of the main experimental task, the two patients' groups presented
      episodic memory, working memory and executive impairments but episodic memory was
      more severely impaired in KS. Both AL and KS exhibited label learning deficits
      but KS were more severely impaired than AL. The episodic memory results were the
      main factor accounting for label learning performance when the three groups were
      pooled together. When examined within each group, the correlation was significant
      in CS and AL but not in KS. Only KS exhibited impaired category and feature
      learning results. Episodic memory did not account for category and feature
      learning performance. New label learning may be equivalent to that of proper
      names, requiring the involvement of episodic memory notably to arbitrarily
      associate a meaningless word with a specific identity. However, when episodic
      memory is severely impaired like in KS, an alternative neocortical learning
      route, bypassing episodic memory, may be invoked. Category and feature seem to be
      acquired independently of episodic memory. The specific impairment in category
      and feature learning in KS may therefore reflect a genuine deficit of semantic
      memory in Korsakoff's syndrome.

PMID- 19154749
TI  - Visual search patterns in neglect: comparison of peripersonal and extrapersonal
      space.
AB  - Previous studies of visual search patterns in visuospatial neglect have analyzed
      shifts of attention during search tasks using eye tracking technology and verbal
      reports. The purpose of the present study was to replicate and extend upon
      reported parameters of visual scanning patterns of neglect patients in
      peripersonal space (within arms reach) and to examine whether similar patterns of
      visual search are also apparent in extrapersonal space (beyond arms reach). Using
      a simple verbal visual search and target detection paradigm right-hemisphere
      stroke participants, with and without neglect, and healthy older volunteers named
      targets on scanning sheets placed in peripersonal and extrapersonal space. The
      healthy controls and right-hemisphere stroke group without neglect showed similar
      'reading' type strategies, while the neglect group displayed an unsystematic
      search pattern, during search in both peripersonal and extrapersonal space. Group
      comparisons of search parameters support the presence of multiple cognitive
      deficits affecting the complex visual search patterns of neglect patients,
      including a rightward attentional bias, a reduced spatial scale of attention
      (local processing bias), and a deficit of working memory affecting both near and
      far space search. Ventral visual stream damage and neglect, however, were related
      to slower target report rate and more misidentification errors in extrapersonal
      space. The ease of administration of this verbal target detection task in both
      peripersonal and extrapersonal space, and the relationship of the measures
      produced to theorized attentional and executive deficits in neglect, provide
      impetus for further research on the severity and independence of individual
      scanning deficits in neglect.

PMID- 19154750
TI  - Behavioral and functional neuroanatomical correlates of anterograde
      autobiographical memory in isolated retrograde amnesic patient M.L.
AB  - Patient M.L. [Levine, B., Black, S. E., Cabeza, R., Sinden, M., Mcintosh, A. R.,
      Toth, J. P., et al. (1998). Episodic memory and the self in a case of isolated
      retrograde amnesia. Brain, 121, 1951-1973], lost memory for events occurring
      before his severe traumatic brain injury, yet his anterograde (post-injury)
      learning and memory appeared intact, a syndrome known as isolated or focal
      retrograde amnesia. Studies with M.L. demonstrated a dissociation between
      episodic and semantic memory. His retrograde amnesia was specific to episodic
      autobiographical memory. Convergent behavioral and functional imaging data
      suggested that his anterograde memory, while appearing normal, was accomplished
      with reduced autonoetic awareness (awareness of the self as a continuous entity
      across time that is a crucial element of episodic memory). While previous
      research on M.L. focused on anterograde memory of laboratory stimuli, in this
      study, M.L.'s autobiographical memory for post-injury events or anterograde
      autobiographical memory was examined using prospective collection of
      autobiographical events via audio diary with detailed behavioral and functional
      neuroanatomical analysis. Consistent with his reports of subjective disconnection
      from post-injury autobiographical events, M.L. assigned fewer "remember" ratings
      to his autobiographical events than comparison subjects. His generation of event
      specific details using the Autobiographical Interview [Levine, B., Svoboda, E.,
      Hay, J., Winocur, G., & Moscovitch, M. (2002). Aging and autobiographical memory:
      dissociating episodic from semantic retrieval. Psychology and Aging, 17, 677-689]
      was low, but not significantly so, suggesting that it is possible to generate
      episodic-like details even when re-experiencing of those details is compromised.
      While listening to the autobiographical audio diary segments, M.L. showed reduced
      activation relative to comparison subjects in midline frontal and posterior nodes
      previously identified as part of the autobiographical memory network. Reductions
      were also evident in M.L. in association with personal semantic stimuli (e.g.,
      recordings describing personal habits and routines). These data suggest an
      association between M.L.'s impoverished recollection of autobiographical material
      and reduced activation in midline sectors of the autobiographical memory network
      that support the autonoetic, first-person element of episodic memory.

PMID- 19154751
TI  - Attention for action? Examining the link between attention and visuomotor control
      deficits in a patient with optic ataxia.
AB  - The classic definition of 'pure' optic ataxia suggests that these patients'
      visuomotor impairments are independent of perceptual or attentional deficits.
      More recent work suggests that some patients with optic ataxia also have
      difficulty attending to targets in their ataxic field. Thus, an important
      question is whether these attentional deficits might be related to the well-known
      problems in visuomotor control evident in these patients. To investigate this
      question we had controls (N=5) and CF, a patient with optic ataxia in his left
      visual field, perform tasks that required them to detect or reach towards targets
      presented in either central vision, or at different target eccentricities in the
      periphery. As expected, CF was less accurate than controls when reaching to
      targets in his ataxic (left) visual field, and was much slower than controls to
      detect the presence of targets in his ataxic field. The reaction times to lift
      the hand in the pointing and the detecting conditions were correlated in the
      ataxic field of patient CF, suggesting a common attentional deficit in both
      tasks. Importantly, although CF was slower to detect targets in the ataxic field,
      and less accurate to reach towards those same targets, the two deficits did not
      follow the same pattern. Specifically, only reaching errors in the ataxic field
      were strongly modulated by target eccentricity. These results suggest that dorsal
      posterior parietal lesions result in attention and visuomotor control problems in
      optic ataxia that arise from damage to independent mechanisms.

PMID- 19154752
TI  - Structural analysis and antitussive evaluation of five novel esters of
      verticinone and bile acids.
AB  - Shedan-Chuanbei powder, a complex of traditional Chinese medicine preparation,
      which consists of Snake Bile (Chinese name "Shedan") and Fritillariae Cirrhosae
      (Chinese name "Chuanbei"), is the most popular antitussive and expectorant
      formulation in Chinese communities. However, the clinical application of Shedan
      Chuanbei powder is now stringently limited because of the shortage of the two
      crude medicinal materials, especially for the sake of animal protection. In
      addition, the inherent defects of the most of the complex of traditional Chinese
      medicine such as the indistinct basal pharmacodynamic materials and the
      difficulties in quality control had blocked them heading into the international
      medicinal market. So we attempted to seek new substitute for Shedan-Chuanbei
      powder for antitussive drugs. In order to gain some new compounds with better
      bioactivity and attenuated toxicity, we tried to combine two kinds of drugs
      through ester bond. Enlightened with "combination principle" in drug discovery,
      we synthesized five novel esters of verticinone and bile acids, both of which are
      the major bioactive components in Shedan-Chuanbei powder. We then evaluated the
      antitussive activity and the acute toxicity of the five ester-linked compounds.
      The five ester-linked compounds had much more potent antitussive activity and
      expectorant activity than single bile acids at the same doses, and had equivalent
      antitussive activity and expectorant activity in comparison with about double
      moles dose of the monomer verticinone. Especially, cholic acid-verticinone ester
      had much more potent antitussive effects than the monomer verticinone or cholic
      acid at the same dose. A further acute toxicity study showed that the LD(50)
      values of the five ester-linked compounds exceeded 3.5g/kg by intraperitoneal
      injection in mice. Based on the studies of pharmacology and acute toxicity, the
      five ester-linked compounds have synergic pharmacodynamic action and attenuated
      toxicity compared with single verticinone and single bile acids.

PMID- 19154753
TI  - Non-canonical reading: reply to Rayner, Pollatsek, Liversedge and Reichle (2008).

PMID- 19154755
TI  - Sunbed use in the Danish population in 2007: a cross-sectional study.
AB  - BACKGROUND: In Denmark, the incidence of all types of skin cancer, including
      malignant melanoma, has been increasing since the 1960s. Exposure to ultraviolet
      (UV) radiation is the main preventable cause of skin cancer. We describe current
      sunbed use in the Danish population. METHODS: A population-based sample of 3437
      persons aged 15-59 years completed a questionnaire that included items on
      artificial and natural exposure to UV. We examined relations between sunbed use,
      outdoor tanning, knowledge about associated health risks and demographic factors
      with logistic regression analysis. RESULTS: Within the past 12 months, 29% of all
      Danes aged 15-59 had used a sunbed, including 59% females aged 15-19, even though
      knowledge about the relation between exposure to UV and cancer was more frequent
      in this group. A larger proportion of persons aged 15-18 had first used a sunbed
      before the age of 14 than older groups. Single males, frequent outdoor
      sunbathers, persons who experienced sunburns and less educated persons were more
      likely to use sunbeds. CONCLUSIONS: Future campaigns to reduce the Danes sunbed
      use should target initiation by young people and the high prevalence among them.
      The results suggest a legislative solution, with a minimum age of 18 years for
      indoor tanning.

PMID- 19154754
TI  - Nuclear lamins and chromatin: when structure meets function.

PMID- 19154756
TI  - Nitric oxide production and nitric oxide synthase type 2 expression by cotton rat
      (Sigmodon hispidus) macrophages reflect the same pattern as human macrophages.
AB  - Our knowledge of the antibacterial role of nitric oxide (NO) during infection is
      based on studies of murine macrophages, which secrete large amounts of NO. In
      contrast, human macrophages produce very little NO and its relevance as an
      antibacterial mediator during infection of humans is uncertain. We have defined
      bone marrow-derived macrophages from cotton rats (Sigmodon hispidus). These
      macrophages display phenotypical and functional characteristics similar to other
      rodent and human macrophages. The most interesting finding was the low level of
      NO production which is in contrast to findings for murine macrophages, but
      consistent with those of humans. In spite of these low levels, inhibition of NO
      production led to a decrease in killing of bacteria. Cotton rats are highly
      susceptible to a variety of human pathogens and therefore offer a rodent model of
      infectious diseases with similar characteristics to humans in terms of NO
      production.

PMID- 19154759
TI  - Neural basis of psychosis-related behaviour in the infection model of
      schizophrenia.
AB  - Maternal infection during pregnancy is a notable risk factor for the offspring to
      develop severe neuropsychiatric disorders, including schizophrenia. One prevalent
      hypothesis suggests that infection-induced disruption of early prenatal brain
      development predisposes the organism for long-lasting structural and functional
      brain abnormalities, leading to the emergence of psychopathological behaviour in
      adulthood. The feasibility of this causal link has received considerable support
      from several experimental models established in both rats and mice. In this
      review, we provide an integrative summary of the long-term neuropathological
      consequences of prenatal exposure to infection and/or inflammation as identified
      in various experimental models of prenatal immune challenge. In addition, we
      highlight how abnormalities in distinct brain areas and neurotransmitter systems
      following prenatal immune activation may provide a neural basis for the emergence
      of specific forms of psychosis-related behaviour. Specifically, we suggest that
      prenatal infection-induced imbalances in the mesolimibic and mesocortical
      dopamine pathways may constitute critical neural mechanisms for disturbances in
      sensorimotor gating, abnormalities in selective associative learning and
      hypersensitivity to psychostimulant drugs. On the other hand, the emergence of
      working memory deficiency following prenatal immune challenge may be crucially
      linked to the concomitant disruption of GABAergic and glutamatergic functions in
      prefrontal cortical and hippocampal structures. Notably, many of the identified
      neuronal abnormalities are directly implicated in the neuropathology of
      schizophrenia. The findings from prenatal infection models of schizophrenia thus
      provide considerable experimental evidence for the assumption that prenatal
      exposure to infection and/or inflammation is a relevant environmental link to
      specific neuronal abnormalities underlying psychosis-related behaviour in humans.

PMID- 19154758
TI  - Intracerebroventricular injections of the enteric bacterial metabolic product
      propionic acid impair cognition and sensorimotor ability in the Long-Evans rat:
      further development of a rodent model of autism.
AB  - Propionic acid (PPA) is a dietary short chain fatty acid and a metabolic end
      product of enteric bacteria. Intracerebroventricular (ICV) injections of PPA can
      result in brain and behavioral abnormalities in rats similar to those seen in
      humans suffering from autism. To evaluate cognition and sensorimotor ability in
      the PPA model, male Long-Evans hooded rats received ICV injection of PPA or
      control compounds prior to behavioral testing in water maze and beam tasks.
      Compared to controls, PPA-treated rats were impaired in the water maze task as
      indicated by an unusual pattern of mild or no impairment during spatial
      acquisition training, but marked impairment during spatial reversal training. PPA
      treated rats were also impaired on the beam task. Neuropathological analysis from
      PPA-treated rats revealed an innate neuroinflammatory response. These findings
      add to evidence that PPA can change the brain and behavior in the laboratory rat
      consistent with symptoms of human autism.

PMID- 19154757
TI  - Mechanisms of chronic central neuropathic pain after spinal cord injury.
AB  - Not all spinal contusions result in mechanical allodynia, in which non-noxious
      stimuli become noxious. The studies presented use the NYU impactor at 12.5 mm
      drop or the Infinite Horizons Impactor (150 kdyn, 1 s dwell) devices to model
      spinal cord injury (SCI). Both of these devices and injury parameters, if done
      correctly, will result in animals with above level (forelimb), at level (trunk)
      and below level (hindlimb) mechanical allodynia that model the changes in evoked
      somatosensation experienced by the majority of people with SCI. The sections are
      as follows: 1) Mechanisms of remote microglial activation and pain signaling in
      "below-level" central pain 2) Intracellular signaling mechanisms in central
      sensitization in "at-level" pain 3) Peripheral sensitization contributes to
      "above level" injury pain following spinal cord injury and 4) Role of reactive
      oxygen species in central sensitization in regional neuropathic pain following
      SCI. To summarize, differential regional mechanisms contribute to the regional
      chronic pain states. We propose the importance of understanding the mechanisms in
      the differential regional pain syndromes after SCI in the chronic condition.
      Targeting regional mechanisms will be of enormous benefit to the SCI population
      that suffer chronic pain, and will contribute to better treatment strategies for
      other chronic pain syndromes.

PMID- 19154760
TI  - Carnosine inhibits high glucose-induced mesangial cell proliferation through
      mediating cell cycle progression.
AB  - Increased mesangial cell proliferation is one of the major pathologic features in
      the early stage of diabetic nephropathy (DN). Carnosine is an endogenously
      synthesized dipeptide that has been reported as a protective factor in diabetic
      nephropathy. However, the underlying mechanism involved in this effect remains to
      be elucidated. In this study, the effect of carnosine on cell proliferation and
      its underlying mechanisms were investigated in cultured rat mesangial cells by
      the methylthiazoletetrazolium (MTT) assay, the 5-bromo-2-deoxy-uridine (BrdU)
      cell proliferation assay, flow cytometry and western blotting. The results showed
      that pretreatment of mesangial cells with carnosine significantly inhibited cell
      proliferation and DNA synthesis in a dose-dependent manner by increasing the cell
      population in G1 and reducing that in S-phase. In addition, carnosine could
      reverse high glucose-induced down-regulation of cyclin-dependent kinase inhibitor
      p21 but not that of p27. Furthermore, carnosine could reduce the phosphorylation
      of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated
      protein kinase (p38 MAPK). Taken together, these results suggest that carnosine
      can inhibit mesangial cell proliferation by modulating cell cycle progress,
      indicating that carnosine could be a potential therapeutic agent for the
      prevention of DN in the early stage.

PMID- 19154761
TI  - Insulin-loaded PLGA/cyclodextrin large porous particles with improved
      aerosolization properties: in vivo deposition and hypoglycaemic activity after
      delivery to rat lungs.
AB  - The aim of the present work is to develop large porous particles (LPP) of poly
      (lactide-co-glycolide) (PLGA) containing insulin with optimal aerodynamic
      properties and to test their in vivo potential, in pulmonary delivery. Insulin
      loaded LPP were fabricated by a double emulsion method by aid of hydroxypropyl
      beta-cyclodextrin (HPbetaCD). Conceiving this system for the controlled release
      of insulin to the lungs, the aerosolization properties and the release features
      in simulated lung fluids of PLGA/HPbetaCD/insulin LPP were investigated in depth.
      The technological results show that the combination of appropriate amounts of
      insulin and HPbetaCD plays a crucial role to achieve PLGA/HPbetaCD/insulin LPP
      with the desired bulk and aerodynamic properties, that is a highly porous
      structure, a very low density (0.1 g/ml), an experimental mass mean aerodynamic
      diameter (MMAD(exp)) ranging from 4.01 to 7.00 and a fine particle fraction (FPF)
      estimated to be 26.9-89.6% at the different airflow rates tested (i.e. 30-90
      l/min). Confocal microscopy studies, performed after administration of labeled
      PLGA/HPbetaCD/insulin LPP to the rat lung by means of a low-scale dry powder
      inhaler (DPI), suggest that particles reach alveoli and remain in situ after
      delivery. The pharmacological effect of PLGA/HPbetaCD/insulin LPP was confirmed
      by dose-response studies performed on both normoglycaemic and streptozotocin
      induced diabetic rats. While insulin solutions administered via pulmonary route
      are unable to cause a significant hypoglycaemic effect, insulin delivered through
      PLGA/HPbetaCD/insulin LPP at the same doses (0.5-4.0 IU/kg) significantly reduces
      blood glucose level as a function of the administered dose in both animal models.
      The developed LPP, tested in hyperglycaemic rats at evident pathological
      conditions, exerts a very significant and longer hypoglycaemic effect even at
      insulin doses as low as 0.5 IU/kg (about 0.5 mg of PLGA/HPbetaCD/insulin LPP per
      rat) as compared to a insulin solution. Taken together, our results support the
      viability of a dry powder formulation based on biodegradable LPP for the
      controlled release of insulin to the lungs. In vivo data show that
      PLGA/HPbetaCD/insulin LPP are able to reach alveoli, release insulin, which is
      absorbed in its bioactive form.

PMID- 19154762
TI  - Thermally triggered intracellular explosion of volume transition nanogels for
      necrotic cell death.
AB  - Here we report a novel class of super-expandable smart nanogels that undergo nano
      to micro-scale volume transition in response to temperature change, applicable
      for thermally triggered death of cancer cells. The nanogels fabricated by light
      cross-linking between oligo(L-lactic acid)-poly(ethylene oxide)-poly(propylene
      oxide)-poly(ethylene oxide)-oligo(L-lactic acid) and poly(ethylene glycol)
      grafted poly(L-lysine) exhibited a reversible volume transition from
      approximately 150 nm at 37 degrees C to approximately 1.4 microm at 15 degrees C.
      The abrupt and dramatic intracellular volume expansion of the nanogels upon the
      brief cold-shock treatment severely damaged sub-cellular self-assembled network
      architectures including cytoskeleton and vesicular membranes and physically
      ruptured cellular membrane structures, resulting in necrotic cell death. The
      smart "nanobomb" detonated by external stimuli could be used to effectively
      induce traumatic death of cells.

PMID- 19154763
TI  - Effective GDNF brain delivery using microspheres--a promising strategy for
      Parkinson's disease.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has shown promise in the
      treatment of neurodegenerative disorders of basal ganglia origin such us
      Parkinson's disease (PD). In this study, we investigated the neurorestorative
      effect of controlled GDNF delivery using biodegradable microspheres in an animal
      model with partial dopaminergic lesion. Microspheres were loaded with N
      glycosylated recombinant GDNF and prepared using the Total Recirculation One
      Machine System (TROMS). GDNF-loaded microparticles were unilaterally injected
      into the rat striatum by stereotaxic surgery two weeks after a unilateral partial
      6-OHDA nigrostriatal lesion. Animals were tested for amphetamine-induced
      rotational asymmetry at different times and were sacrificed two months after
      microsphere implantation for immunohistochemical analysis. The putative presence
      of serum IgG antibodies against rat glycosylated GDNF was analyzed for addressing
      safety issues. The results demonstrated that GDNF-loaded microspheres, improved
      the rotational behavior induced by amphetamine of the GDNF-treated animals
      together with an increase in the density of TH positive fibers at the striatal
      level. The developed GDNF-loaded microparticles proved to be suitable to release
      biologically active GDNF over up to 5 weeks in vivo. Furthermore, none of the
      animals developed antibodies against GDNF demonstrating the safety of
      glycosylated GDNF use.

PMID- 19154764
TI  - Recent advances in cancer chemotherapy: current strategies, pharmacokinetics, and
      pharmacogenomics.

PMID- 19154765
TI  - A qualitative investigation into the opinions of adolescent females regarding
      their body image concerns and dieting practices in the Republic of Ireland (ROI).
AB  - The aim of this study was to investigate the opinions of female adolescents
      living in the ROI on issues relating to body image and dietary practice. A
      qualitative study was selected to enable the issues to be explored in depth.
      Sixteen focus groups were executed with adolescent females (n=124) aged 15-16
      years. Data collection took place during class time in both rural and urban
      schools in the ROI. Data were analysed using a qualitative thematic methodology,
      namely framework analysis. High levels of body dissatisfaction existed and
      dieting was found to be prevalent. The influence of media celebrities was
      significant. The girls not only aspired to be like them in terms of physique but
      also followed their alleged dieting regimes in detail. Peers also influenced body
      dissatisfaction and dieting practices. Consequently, eating habits were altered
      to accommodate this quest for thinness with a tendency to skip main meals as part
      of the dieting practice while maintaining an unhealthy snacking pattern. The
      results are of concern as the adolescent females were utilising unhealthy methods
      of weight control such as skipping meals and fasting in their quest to obtain a
      thin physique. A slim body image was deemed important for peer acceptance; hence
      'crash' dieting was in existence. This mindset and the resultant dietary
      practices may have negative health consequences during both adolescence and later
      life. School interventions targeting adolescent females and focusing on healthy
      eating and body image are therefore urgently required.

PMID- 19154766
TI  - Degradation of leucomyosuppressin by enzymes in the hemolymph and midgut of
      Lacanobia oleracea and Spodoptera littoralis (Lepidoptera: Noctuidae) larvae.
AB  - The degradation of 2 nmol synthetic leucomyosuppressin (LMS) by enzymes of the
      hemolymph, midgut lumen and midgut tissues of both Lacanobia oleracea and
      Spodoptera littoralis was investigated using reversed-phase high-performance
      liquid chromatography together with matrix assisted laser desorption ionization
      time of flight mass spectrometry (MALDI-TOF MS). Degradation of LMS in diluted
      hemolymph of L. oleracea and S. littoralis was not rapid, t(1/2)=65.4 and 13.1
      min, respectively, due to carboxypeptidase(s) and endopeptidase(s) present in the
      hemolymph. There was also some aminopeptidase activity in the hemolymph of both
      species. However, LMS was rapidly degraded by the diluted contents of the midgut
      lumen of L. oleracea and S. littoralis, t(1/2)=0.5 and 2.2 min, respectively. The
      enzymes most likely responsible were trypsin-like serine protease(s) and
      carboxypeptidase(s). Degradation of LMS by midgut tissues containing 5 microg
      protein was not rapid in L. oleracea or S. littoralis, t(1/2)=40.7 and 69.8 min,
      respectively. The most abundant degradation products probably resulted from
      carboxypeptidase activity, but some aminopeptidase activity was also detected.

PMID- 19154767
TI  - Selective cancer cell cytotoxicity of enantiomeric 9-mer peptides derived from
      beetle defensins depends on negatively charged phosphatidylserine on the cell
      surface.
AB  - Four enantiomeric 9-mer peptides named d-peptide A, B, C and D were designed and
      synthesized on the basis of 43-mer insect defensins from two beetles. The d-9-mer
      peptides maintained bacterial membrane disruptive activity similar to the
      original peptides and also showed various extents of growth inhibitory activity
      against different cancer cell lines. Of these peptides, d-peptide B exhibited the
      highest selective cancer cell cytotoxicity against the mouse myeloma cell line,
      P3-X63-Ag8.653. Flow cytometric and scanning electron microscopic analysis
      revealed d-peptide B disrupts mouse myeloma membrane construction, whereas no
      cytotoxic effect on normal leukocytes was observed. Moreover, a strong
      correlation between negatively charged phosphatidylserine (PS) density in cancer
      cell membrane surface and sensitivity to d-9-mer peptides were observed in
      various cancer cell lines. These results suggest that d-9-mer peptides have
      negative charge-dependent selective cancer cell cytotoxicity targeting PS in the
      cancer cell membrane. In addition, synergic growth inhibitory activity against
      mouse myeloma was observed in combinations of d-peptide B and dexamethasone.
      These results suggest d-9-mer peptides are promising candidates for novel
      anticancer drugs.

PMID- 19154768
TI  - The effect of energy restriction during pregnancy on obesity-related peptide
      hormones in rat offspring.
AB  - It has been proposed that fetal exposure to environmental stressors, such as
      undernutrition, during critical periods of development may lead to adaptations
      that permanently change the structure and function of the body. These adaptations
      may be important for immediate survival during fetal development, but can
      predispose to disease in later life. We designed a pilot study investigating the
      effect of fetal undernutrition on the obesity-related peptides adiponectin,
      ghrelin, leptin and resistin levels in rat. We also wanted to explore changes in
      lipid and insulin metabolism. Sprague-Dawley rats were randomly assigned to three
      dietary treatment groups on day 4 of gestation. The control group was fed ad
      libitum and the food-restricted rats received either 75% or 50% of ad libitum
      food intake until parturition. Serum levels of obesity-related peptides as well
      as lipid and insulin levels were measured from 1-month-old pups. Serum resistin
      concentrations were higher in both food-restricted groups and serum adiponectin
      concentration was lower in the 50% food-restricted group compared to the control
      group. Serum total cholesterol levels were significantly higher in both food
      restricted groups. These results indicate that undernutrition during fetal
      development may lead to unfavorable changes in obesity-related peptide hormones
      as well as evoking adverse changes in serum cholesterol levels. The observed
      changes may predispose to insulin resistance and significantly increase the risk
      of developing cardiovascular disease in later life.

PMID- 19154769
TI  - Diversity of neurodegenerative processes in the model of brain cortex tissue
      ischemia.
AB  - Stroke is known to induce massive cell death in the ischemic brain. Either
      necrotic or apoptotic types of cell death program were observed in neurons in
      zone of ischemia. We suggest that spatial heterogeneity of glucose and oxygen
      distribution plays a crucial role in this phenomenon. In order to elucidate the
      role of glucose and oxygen in ischemic neurons choice of cell death pathway,
      conditions corresponding to different areas of insult were reproduced in vitro in
      the model of surviving brain cortex tissue slices. Three zones were modeled in
      vitro by varying glucose and oxygen concentration in surviving slices incubation
      media. Modeled ischemic area I (MIA I) was corresponded to the center of
      suggested ischemic zone where the levels of glucose and oxygen were considered to
      be extremely low. MIA II was assigned as intermediate area where oxygen
      concentration was still very low but glucose was present (this area was also
      divided into two sub-areas MIA IIa and MIA IIb with physiologically low (5mM) and
      normal (10mM) level of glucose respectively). MIA III was considered as a
      periphery area where glucose concentration was close to physiological level and
      high level of ROS production had been induced by reoxygenation after anoxia.
      Analysis of molecular mechanisms of cell death in MIA I, IIa, IIb and III was
      carried out. Cell death in MIA I was found to proceed by necrotic manner.
      Apoptosis characterized by cyt c release, caspase 3 activation and
      internucleosomal DNA fragmentation was observed in MIA III. Cell death in MIA II
      was accompanied by several (not all) hallmarks of apoptosis. Mechanisms of cell
      death in MIA IIa and MIA IIb were found to be different. Internucleosomal DNA
      fragmentation in MIA IIa but not in MIA IIb was sensitive to glycine (5mM),
      inhibitor of NMDA receptor MK-801 (10microM) and PTP inhibitor cyclosporine A
      (10microM). Activation of caspase 3 was detected in MIA IIb but not in MIA IIa.
      However cytochrome c release was observed neither in MIA IIa nor in MIA IIb. In
      MIAs II-III apoptosis was accompanied by uncoupling of oxidative phosphorylation,
      which was induced by rise of intracellular Ca(2+) and intensive ROS production.
      Results obtained in present study allow us to propose existence of at least four
      molecular pathways of cell death development in brain ischemic zone. The choice
      of cell death pathway is determined by oxygen and glucose concentration in the
      particular area of the ischemic zone.

PMID- 19154770
TI  - Ubiquitin dimers control the hydrolase activity of UCH-L3.
AB  - Ubiquitin (Ub) carboxy terminal hydrolase (UCH)-L1 and UCH-L3 are two of the
      deubiquitinating enzymes expressed in the brain. Both gad mice, which lack UCH-L1
      expression and Uchl3 knockout mice exhibit neurodegeneration, although at
      distinct areas. These phenotypes indicate the importance of UCH-L1 and UCH-L3 in
      the regulation of the central nervous system. However, molecular substrates and
      the molecular regulators of UCH-L1 and UCH-L3 remain poorly identified. Here we
      show that Ub dimers interact non-covalently with UCH-L3 in vitro and in cells.
      These interactions were not observed with UCH-L1 in cells. In vitro, K48-linked
      Ub dimers pronouncedly inhibited the hydrolase activity of UCH-L3, while mono-Ub,
      a previously identified interacting protein, inhibited the hydrolase activity of
      UCH-L1. These results indicate that mono-Ub and Ub dimers may regulate the
      enzymatic functions of UCH-L1 and UCH-L3, respectively, in vivo.

PMID- 19154771
TI  - Proteomic and histochemical analysis of proteins involved in the dying-back-type
      of axonal degeneration in the gracile axonal dystrophy (gad) mouse.
AB  - Local axonal degeneration is a common pathological feature of peripheral
      neuropathies and neurodegenerative disorders of the central nervous system,
      including Alzheimer's disease, Parkinson's disease, and stroke; however, the
      underlying molecular mechanism is not known. Here, we analyzed the gracile axonal
      dystrophy (gad) mouse, which displays the dying-back-type of axonal degeneration
      in sensory neurons, to find the molecules involved in the mechanism of axonal
      degeneration. The gad mouse is analogous to a null mutant of ubiquitin carboxyl
      terminal hydrolase L1 (UCH-L1). UCH-L1 is a deubiquitinating enzyme expressed at
      high levels in neurons, as well as testis and ovary. In addition, we recently
      discovered a new function of UCH-L1-namely to bind to and stabilize mono
      ubiquitin in neurons, and found that the level of mono-ubiquitin was decreased in
      neurons, especially in axons of the sciatic nerve, in gad mice. The low level of
      ubiquitin suggests that the target proteins of the ubiquitin proteasome system
      are not sufficiently ubiquitinated and thus degraded in the gad mouse; therefore,
      these proteins may be the key molecules involved in axonal degeneration. To
      identify molecules involved in axonal degeneration in gad mice, we compared
      protein expression in sciatic nerves between gad and wild-type mice at 2 and 12
      weeks old, using two-dimensional difference gel electrophoresis. As a result, we
      found age-dependent accumulation of several proteins, including glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) and 14-3-3, in gad mice compared with wild-type
      mice. Histochemical analyses demonstrated that GAPDH and 14-3-3 were localized
      throughout axons in both gad and wild-type mice, but GAPDH accumulated in the
      axons of gad mice. Recently, it has been suggested that a wide range of
      neurodegenerative diseases are characterized by the accumulation of intracellular
      and extracellular protein aggregates, and it has been reported that oxidative
      stress causes the aggregation of GAPDH. Furthermore, histochemical analysis
      demonstrated that sulfonated GAPDH, a sensor of oxidative stress that elicits
      cellular dysfunction, was expressed in the axons of gad mice, and 4-hydroxy-2
      nonenal, a major marker of oxidative stress, was also only detected in gad mice.
      Our findings suggest that GAPDH may participate in a process of the dying-back
      type of axonal degeneration in gad mice and may provide valuable insight into the
      mechanisms of axonal degeneration.

PMID- 19154773
TI  - Different pattern of brain pro-/anti-oxidant activity between depleted and
      enriched uranium in chronically exposed rats.
AB  - Uranium is not only a heavy metal but also an alpha particle emitter. The main
      toxicity of uranium is expected to be due to chemiotoxicity rather than to
      radiotoxicity. Some studies have demonstrated that uranium induced some
      neurological disturbances, but without clear explanations. A possible mechanism
      of this neurotoxicity could be the oxidative stress induced by reactive oxygen
      species imbalance. The aim of the present study was to determine whether a
      chronic ingestion of uranium induced anti-oxidative defence mechanisms in the
      brain of rats. Rats received depleted (DU) or 4% enriched (EU) uranyl nitrate in
      the drinking water at 2mg(-1)kg(-1)day(-1) for 9 months. Cerebral cortex analyses
      were made by measuring mRNA and protein levels and enzymatic activities. Lipid
      peroxidation, an oxidative stress marker, was significantly enhanced after EU
      exposure, but not after DU. The gene expression or activity of the main
      antioxidant enzymes, i.e. superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GPx), increased significantly after chronic exposure to
      DU. On the contrary, oral EU administration induced a decrease of these
      antioxidant enzymes. The NO-ergic pathway was almost not perturbed by DU or EU
      exposure. Finally, DU exposure increased significantly the transporters (Divalent
      Metal-Transporter1; DMT1), the storage molecule (ferritin) and the ferroxidase
      enzyme (ceruloplasmin), but not EU. These results illustrate that oxidative
      stress plays a key role in the mechanism of uranium neurotoxicity. They showed
      that chronic exposure to DU, but not EU, seems to induce an increase of several
      antioxidant agents in order to counteract the oxidative stress. Finally, these
      results demonstrate the importance of the double toxicity, chemical and
      radiological, of uranium.

PMID- 19154774
TI  - GISP increases neurotransmitter receptor stability by down-regulating ESCRT
      mediated lysosomal degradation.
AB  - GPCR interacting scaffold protein (GISP) is a multi-domain brain-specific
      scaffold protein that can regulate GABA(B) receptor complexes by both enhancing
      their surface expression and by inhibiting their lysosomal degradation. GISP
      retards degradation of GABA(B) receptors through its interaction with tumour
      susceptibility gene 101 (TSG101), a member of the endosomal sorting complex
      required for transport (ESCRT) lysosomal sorting machinery. We show that in
      addition to GABA(B), GISP exerts a more general role to increase the steady-state
      levels of several neurotransmitter receptors. Further, GISP delays TSG101
      dependent agonist-induced EGFR down-regulation in human embryonic kidney (HEK)
      293 cells whereas a mutant GISP lacking the TSG101 binding domain has no effect.
      These data suggest that GISP acts as a negative regulator of TSG101-dependent
      lysosomal degradation and plays an important role in determining the availability
      of neurotransmitter receptors.

PMID- 19154775
TI  - Nociceptive vascular reflexes evoked by scorpion venom modulate cardiorespiratory
      parameters involving vanilloid receptor 1 in anaesthetised rats.
AB  - Involvement of vanilloid and 5-HT(3) receptors in the cardiorespiratory reflexes
      evoked by intra-arterial (i.a.) injection of Mesobuthus tamulus (BT) venom was
      examined. In anaesthetised rats, blood pressure, respiratory excursions and ECG
      were recorded for 60min after the injection of venom in the absence or presence
      of antagonists. Injection of BT venom (1mg/kg, i.a.) produced alterations in
      respiratory frequency (RF), blood pressure (BP) and heart rate (HR). The changes
      in RF were manifested as immediate increase (40%) followed by a decrease (40%)
      and subsequent sustained increase (60%). In case of BP, the increase began around
      40s, peaked at 5min (50%) and remained above the initial level subsequently. The
      bradycardiac response began around 5min which peaked (50% of the initial) around
      25min and remained at that level. Thus, exhibiting immediate-tachypnoeic,
      intermediate-hypertensive and delayed-bradycardiac responses. Pretreatment with
      lignocaine, blocked the respiratory responses and attenuated the pressor
      responses evoked by venom. Pretreatment with capsazepine, vanilloid receptor 1
      (VR1) antagonist, antagonized all the three parameters of cardiorespiratory
      responses evoked by venom. Whereas, ondansetron (5-HT(3) antagonist) attenuated
      the pressor and bradycardiac responses significantly but not the respiratory
      responses. These observations indicate that the cardiorespiratory changes induced
      by intra-arterial injection of venom are carried by afferents in addition to
      somatic nerves, involving mainly VR1 receptors and partially by 5-HT(3)
      receptors.

PMID- 19154776
TI  - Cryptotanshinone, a compound from Salvia miltiorrhiza modulates amyloid precursor
      protein metabolism and attenuates beta-amyloid deposition through upregulating
      alpha-secretase in vivo and in vitro.
AB  - The amyloid precursor protein (APP) is cleaved enzymatically by non-amyloidogenic
      and amyloidogenic pathways. alpha-Secretase cleaves APP within beta-amyloid
      protein (Abeta) sequence, resulting in the release of a secreted fragment of APP
      (sAPPalpha) and precluding Abeta generation. Cryptotanshinone (CTS), an active
      component of the medicinal herb Salvia miltiorrhiza, has been shown to improve
      learning and memory in several pharmacological models of Alzheimer's disease
      (AD). However, the effects of CTS on the Abeta plaque pathology and the APP
      processing in AD are unclear. Here we reported that CTS strongly attenuated
      amyloid plaque deposition in the brain of APP/PS1 transgenic mice. In addition,
      CTS significantly improved spatial learning and memory in APP/PS1 mice assessed
      by the Morris water maze testing. To define the exact molecular mechanisms
      involved in the beneficial effects of CTS, we investigated the effects of the CTS
      on APP processing in rat cortical neuronal cells overexpressing Swedish mutant
      human APP695. CTS was found to decrease Abeta generation in concentration
      dependent (0-10muM) manner. Interestingly, the N-terminal APP cleavage product,
      sAPPalpha was markedly increased by CTS. Further study showed that alpha
      secretase activity was increased by CTS. Taken together, our results suggested
      CTS improved the cognitive ability in AD transgenic mice and promoted APP
      metabolism toward the non-amyloidogenic products pathway in rat cortical neuronal
      cells. CTS shows a promising novel way for the therapy of AD.

PMID- 19154777
TI  - Salicylate increases the gain of the central auditory system.
AB  - High doses of salicylate, the anti-inflammatory component of aspirin, induce
      transient tinnitus and hearing loss. Systemic injection of 250 mg/kg of
      salicylate, a dose that reliably induces tinnitus in rats, significantly reduced
      the sound evoked output of the rat cochlea. Paradoxically, salicylate
      significantly increased the amplitude of the sound-evoked field potential from
      the auditory cortex (AC) of conscious rats, but not the inferior colliculus (IC).
      When rats were anesthetized with isoflurane, which increases GABA-mediated
      inhibition, the salicylate-induced AC amplitude enhancement was abolished,
      whereas ketamine, which blocks N-methyl-d-aspartate receptors, further increased
      the salicylate-induced AC amplitude enhancement. Direct application of salicylate
      to the cochlea, however, reduced the response amplitude of the cochlea, IC and
      AC, suggesting the AC amplitude enhancement induced by systemic injection of
      salicylate does not originate from the cochlea. To identify a behavioral
      correlate of the salicylate-induced AC enhancement, the acoustic startle response
      was measured before and after salicylate treatment. Salicylate significantly
      increased the amplitude of the startle response. Collectively, these results
      suggest that high doses of salicylate increase the gain of the central auditory
      system, presumably by down-regulating GABA-mediated inhibition, leading to an
      exaggerated acoustic startle response. The enhanced startle response may be the
      behavioral correlate of hyperacusis that often accompanies tinnitus and hearing
      loss.

PMID- 19154778
TI  - Mechanisms underlying state dependent surface-evoked response patterns.
AB  - Cortical evoked response potentials (ERPs) display a rich set of waveforms that
      are both context and state dependent. However, the mechanisms that underlie state
      dependent ERP patterns are unclear. Determining those mechanisms through analysis
      of single trial ERP waveform signatures may provide insight into the regulation
      of cortical column state and the roles that sleep plays in cortical function. We
      implanted rats with electroencephalogram (EEG) and electromyogram (EMG)
      electrodes to record ERPs and to assess sleep/wake states continuously during 1-2
      s random auditory clicks. Individual cortical auditory ERPs were sorted into one
      of eight behavioral states, and fell into three categories based on amplitude and
      latency characteristics. ERPs within waking and rapid eye movement (REM) sleep
      were predominantly low amplitude and short latency. Approximately 50% of ERPs
      during light quiet sleep (quiet sleep 1 and quiet sleep 2) exhibited low
      amplitude, short latency responses, and the remaining ERPs had high amplitude,
      long latency responses. This distribution was characteristic of EEG fluctuations
      during low frequency delta waves. Significantly more individual ERPs showed very
      low amplitudes during deep quiet sleep (quiet sleep 3 and quiet sleep 4),
      resulting in a lower average ERP. These results support the hypothesis that
      evoked response amplitudes and waveform patterns follow specific EEG patterns.
      Since evoked response characteristics distribute differently across states, they
      could aid our understanding of sleep mechanisms through state-related and local
      neural signaling.

PMID- 19154779
TI  - Modification of ionotropic glutamate receptor-mediated processes in the rat
      hippocampus following repeated, brief seizures.
AB  - The seizure-induced molecular and functional alterations of glutamatergic
      transmission in the hippocampus have been investigated. Daily repeated epileptic
      seizures were induced for 12 days by intraperitoneal administration of 4
      aminopyridine (4-AP; 4.5 mg/kg) in adult Wistar rats. The seizure symptoms were
      evaluated on the Racine's scale. One day after the last injection, the brains
      were removed for in vitro electrophysiological experiments and
      immunohistochemical analysis. The glutamate receptor subunits NR1, NR2A, NR2B,
      GluR1, GluR1(flop), GluR2, and KA-2 were studied using the histoblotting method.
      The semi-quantitative analysis of subunit immunoreactivities in hippocampal
      layers was performed with densitometry. In the hippocampus, increase of GluR1,
      GluR1(flop) and NR2B immunostaining was observed in most of the areas and layers.
      The significant decrease of GluR2 staining intensity was observed in the CA1 and
      dentate gyrus. Calcium permeability of hippocampal neurons was tested by a cobalt
      uptake assay in hippocampal slices. The uptake of cobalt increased in the CA1
      area and dentate gyrus, but not in the CA3 region following 4-AP treatment.
      Effects of AMPA and NMDA (N-methyl-d-aspartate) glutamate receptor antagonists (1
      (4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride
      (GYKI 52466) and D-APV respectively) were measured in hippocampal slices using
      extracellular recording. Analysis of the population spikes revealed the reduced
      effectiveness of the AMPA receptor antagonist GYKI 52466, while the effect of the
      NMDA receptor antagonist d-(2R)-amino-5-phosphonovaleric acid was similar to
      controls. The results demonstrated that repeated convulsions induced structural
      and functional changes in AMPA receptor-mediated transmission, while NMDA and
      kainate receptor systems displayed only alterations in receptor subunit
      composition.

PMID- 19154780
TI  - Ocular surface-evoked Fos-like immunoreactivity is enhanced in trigeminal
      subnucleus caudalis by prior exposure to endotoxin.
AB  - Endotoxin-induced uveitis (EIU) is a common animal model for anterior uveitis in
      humans that causes long-term changes in trigeminal brain stem neurons. This study
      used c-fos immunohistochemistry to assess the effects of different routes of
      administration of endotoxin on activation of trigeminal brain stem neurons
      produced by ocular surface stimulation. A single dose of endotoxin
      (lipopolysaccharide (LPS)) given to male rats by systemic (i.p., 1 mg/kg) or
      intraocular (ivt, 20 microg) routes increased the number of Fos-positive neurons
      in rostral (trigeminal subnucleus interpolaris/subnucleus transition (Vi/Vc)) and
      caudal portions of trigeminal subnucleus caudalis (trigeminal subnucleus
      caudalis/upper cervical spinal cord transition (Vc/C(1-2))) by 20% mustard oil
      (MO) applied to the ocular surface 7 days, but not at 2 days, after LPS compared
      with naive rats. I.c.v. (20 microg) LPS did not affect MO-evoked Fos. To
      determine if the pattern of enhanced Fos expression after systemic LPS also
      depended on the nature of the ocular surface stimulus, additional groups received
      ocular stimulation by 10% histamine or dry eye conditions. Seven days, but not 2
      days, after i.p. LPS both histamine- and dry eye-evoked Fos was increased at the
      Vi/Vc transition, while smaller effects were seen at other regions. These results
      suggested that EIU modulation of trigeminal brain stem neuron activity was
      mediated mainly by peripheral actions of LPS. Enhancement of Fos at the Vi/Vc
      region after MO, histamine and dry eye conditions supports the hypothesis that
      this region integrates innocuous as well as noxious sensory information, while
      more caudal portions of Vc process mainly nociceptive signals from the eye.

PMID- 19154782
TI  - Fearfulness in red junglefowl and domesticated White Leghorn chickens.
AB  - It may be hypothesised that reduced fearfulness has been a major target of
      selection during domestication. We tested 20 domesticated White Leghorn (WL)
      chickens and their ancestors, red junglefowl (RJF), in four different fear tests
      (Open Field, Novel Object, Aerial Predator, and Fear for Humans). The tests were
      designed to measure reactions to different types of potentially fearful stimuli.
      The correlations between durations of the same four variables from each of the
      tests (Stand/sit alert, Locomotion, Fly/jump, and Vocalisation) were analysed
      with principal components analysis (PCA). In the PCA, 33.5% of the variation in
      responses was explained by a single factor, interpreted as a general fear factor.
      Higher scores on this were related to stronger fear reactions. Red junglefowl
      scored significantly higher than White Leghorns on this factor, and also had a
      longer latency to feed in the Fear of Humans-test, used as an independent measure
      of fear in the same tests. The results suggest that selection for low fearfulness
      has been an important element of domestication.

PMID- 19154783
TI  - Sex-specific defence behaviour against brood parasitism in a host with female
      only incubation.
AB  - Nest protection against intruders is an indispensable component of avian parental
      care. In species with biparental care, both mates should evolve nest defence
      behaviour to increase their reproductive success. In most host-parasite systems,
      host females are predicted to have more important roles in nest defence against
      brood parasites, because they typically are primarily responsible for clutch
      incubation. Male antiparasitic behaviour, on the other hand, is often
      underestimated or even not considered at all. Here we investigated sex-specific
      roles in four aspects of great reed warbler (Acrocephalus arundinaceus) nest
      defence against a brood parasite-the cuckoo (Cuculus canorus), namely (1)
      mobbing, (2) nest attendance/guarding, (3) nest checking and (4) egg ejection.
      Using dummy experiments, simulating brood parasitism and by video-monitoring of
      host nests we found that males took the key roles in cuckoo mobbing and nest
      guarding, while females were responsible for nest checking and egg ejection
      behaviours. Such partitioning of parental roles may provide a comprehensive
      clutch protection against brood parasitism.

PMID- 19154781
TI  - Role of endothelial nitric oxide synthetase in arteriogenesis after stroke in
      mice.
AB  - Arteriogenesis supports restored perfusion in the ischemic brain and improves
      long-term functional outcome after stroke. We investigate the role of endothelial
      nitric oxide synthetase (eNOS) and a nitric oxide (NO) donor, (Z)-1-[N-(2
      aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETA-NONOate),
      in promoting arteriogenesis after stroke. Adult wild-type (WT, n=18) and eNOS
      knockout (eNOS(-/-), n=36) mice were subjected to transient (2.5 h) right middle
      cerebral artery occlusion (MCAo) and were treated with or without DETA-NONOate
      (0.4 mg/kg) 24 h after MCAo. Functional evaluation was performed. Animals were
      sacrificed 3 days after MCAo for arterial cell culture studies, or 14 days for
      immunohistochemical analysis. Consistent with previous studies, eNOS(-/-) mice
      exhibited a higher mortality rate (P<0.05, n=18/group) and more severe
      neurological functional deficit after MCAo than WT mice (P<0.05, n=12/group).
      Decreased arteriogenesis, was evident in eNOS(-/-) mice compared with WT mice, as
      demonstrated by reduced vascular smooth muscle cell (VSMC) proliferation,
      arterial density and diameter in the ischemic brain. eNOS(-/-) mice treated with
      DETA-NONOate had a significantly decreased mortality rate and improved functional
      recovery, and exhibited enhanced arteriogenesis identified by increased VSMC
      proliferation, and upregulated arterial density and diameter compared to eNOS(-/
      ) mice after stroke (P<0.05, n=12/group). To elucidate the mechanisms underlying
      eNOS/NO mediated arteriogenesis, VSMC migration was measured in vitro. Arterial
      cell migration significantly decreased in the cultured common carotid artery
      (CCA) derived from eNOS(-/-) mice 3 days after MCAo compared to WT arterial
      cells. DETA-NONOate-treatment significantly attenuated eNOS(-/-)-induced decrease
      of arterial cell migration compared to eNOS(-/-) control artery (P<0.05;
      n=6/group). Using VSMC culture, DETA-NONOate significantly increased VSMC
      migration, while inhibition of NOS significantly decreased VSMC migration
      (P<0.05; n=6/group). Our data indicated that eNOS not only promotes vascular
      dilation but also increases VSMC proliferation and migration, and thereby
      enhances arteriogenesis after stroke. Therefore, increase eNOS may play an
      important role in regulating of arteriogenesis after stroke.

PMID- 19154784
TI  - Impact of age and strain on ischemic brain injury and seizures after carotid
      ligation in immature mice.
AB  - Stroke is an important cause of neurologic injury in the neonatal period and
      frequently results in lifelong neurologic impairments. We reported previously
      that unilateral carotid ligation on postnatal day (P)12 in CD1 mice causes acute
      behavioral seizures and unilateral brain injury and provides a model for neonatal
      stroke in human infants. In the present study we confirmed that behavioral
      seizures observed after ligation on P12 in the CD1 strain are associated with
      rhythmic ictal discharges that show temporal progression on electrocorticograms.
      We also examined the effects of carotid ligation performed at different ages in
      CD1 mice or performed in the C57Bl/6 strain. The right common carotid was ligated
      at P7, P10, P12 or P21 in CD1 mice or at P12 in C57Bl/6 mice. Littermate controls
      received sham surgery. Seizures were rated for 4h after surgery; brain injury was
      scored one week later. In a separate group of P12 CD1 mice, electrocorticographic
      activity was recorded continuously for 4h after carotid ligation or sham surgery.
      Brain injury and cumulative seizure score varied significantly with age (p<0.001)
      and strain (p<0.001). In CD1 mice, injury was greatest after ligation on P10 to
      P12 and seizure score was maximal at P12. Seizure scores were significantly
      correlated with injury after ligation on P10 or P12. C57Bl/6 mice, like C3Heb/FeJ
      mice examined previously, were much less vulnerable to seizures and injury than
      CD1 mice after ligation on P12. This study demonstrates that carotid ligation in
      the CD1 mouse on P12 causes acute electrographic rhythmic discharges that
      correlate with behavioral seizures. We also found that the age at which ligation
      is performed and genetic strain have a strong influence on the severity of
      injury.

PMID- 19154785
TI  - Ultrafine particles from diesel engines induce vascular oxidative stress via JNK
      activation.
AB  - Exposure to particulate air pollution is linked to increased incidences of
      cardiovascular diseases. Ambient ultrafine particles (UFP) from diesel vehicle
      engines have been shown to be proatherogenic in ApoE knockout mice and may
      constitute a major cardiovascular risk in humans. We posited that circulating
      nano-sized particles from traffic pollution sources induce vascular oxidative
      stress via JNK activation in endothelial cells. Diesel UFP were collected from a
      1998 Kenworth truck. Intracellular superoxide assay revealed that these UFP dose
      dependently induced superoxide (O(2)(-)) production in human aortic endothelial
      cells (HAEC). Flow cytometry showed that UFP increased MitoSOX red intensity
      specific for mitochondrial superoxide. Protein carbonyl content was increased by
      UFP as an indication of vascular oxidative stress. UFP also up-regulated heme
      oxygenase-1 (HO-1) and tissue factor (TF) mRNA expression, and pretreatment with
      the antioxidant N-acetylcysteine significantly decreased their expression.
      Furthermore, UFP transiently activated JNK in HAEC. Treatment with the JNK
      inhibitor SP600125 and silencing of both JNK1 and JNK2 with siRNA inhibited UFP
      stimulated O(2)(-) production and mRNA expression of HO-1 and TF. Our findings
      suggest that JNK activation plays an important role in UFP-induced oxidative
      stress and stress response gene expression.

PMID- 19154786
TI  - Reduced amyloidogenic processing of the amyloid beta-protein precursor by the
      small-molecule Differentiation Inducing Factor-1.
AB  - The detection of cell cycle proteins in Alzheimer's disease (AD) brains may
      represent an early event leading to neurodegeneration. To identify cell cycle
      modifiers with anti-Abeta properties, we assessed the effect of Differentiation
      Inducing Factor-1 (DIF-1), a unique, small-molecule from Dictyostelium
      discoideum, on the proteolysis of the amyloid beta-protein precursor (APP) in a
      variety of different cell types. We show that DIF-1 slows cell cycle progression
      through G0/G1 that correlates with a reduction in cyclin D1 protein levels.
      Western blot analysis of DIF-treated cells and conditioned medium revealed
      decreases in the levels of secreted APP, mature APP, and C-terminal fragments.
      Assessment of conditioned media by sandwich ELISA showed reduced levels of
      Abeta40 and Abeta42, also demonstrating that treatment with DIF-1 effectively
      decreases the ratio of Abeta42 to Abeta40. In addition, DIF-1 significantly
      diminished APP phosphorylation at residue T668. Interestingly, site-directed
      mutagenesis of APP residue Thr668 to alanine or glutamic acid abolished the
      effect of DIF-1 on APP proteolysis and restored secreted levels of Abeta.
      Finally, DIF-1 prevented the accumulation of APP C-terminal fragments induced by
      the proteasome inhibitor lactacystin, and calpain inhibitor N-acetyl-leucyl
      leucyl-norleucinal (ALLN). Our findings suggest that DIF-1 affects G0/G1
      associated amyloidogenic processing of APP by a gamma-secretase-, proteasome- and
      calpain-insensitive pathway, and that this effect requires the presence of
      residue Thr668.

PMID- 19154787
TI  - Cloning, purification and characterization of Geobacillus stearothermophilus V
      uroporphyrinogen-III C-methyltransferase: evaluation of its role in resistance to
      potassium tellurite in Escherichia coli.
AB  - The Geobacillus stearothermophilus V cobA gene encoding uroporphyrinogen-III C
      methyltransferase (also referred to as SUMT) was cloned into Escherichia coli and
      the recombinant enzyme was overexpressed and purified to homogeneity. The enzyme
      binds S-adenosyl-L-methionine and catalyzes the production of III methyl
      uroporphyrinogen in vitro. E. coli cells expressing the G. stearothermophilus V
      cobA gene exhibited increased resistance to potassium tellurite and potassium
      tellurate. Site-directed mutagenesis of cobA abolished tellurite resistance of
      the mesophilic, heterologous host and SUMT activity in vitro. No methylated,
      volatile derivatives of tellurium were found in the headspace of tellurite
      exposed cobA-expressing E. coli, suggesting that the role of SUMT
      methyltransferase in tellurite(ate) detoxification is not related to tellurium
      volatilization.

PMID- 19154788
TI  - Bacopa monniera leaf extract ameliorates hypobaric hypoxia induced spatial memory
      impairment.
AB  - Hypobaric hypoxia induced memory impairment has been attributed to several
      factors including increased oxidative stress, depleted mitochondrial
      bioenergetics, altered neurotransmission and apoptosis. This multifactorial
      response of the brain to hypobaric hypoxia limits the use of therapeutic agents
      that target individual pathways for ameliorating hypobaric hypoxia induced memory
      impairment. The present study aimed at exploring the therapeutic potential of a
      bacoside rich leaf extract of Bacopa monniera in improving the memory functions
      in hypobaric conditions. The learning ability was evaluated in male Sprague
      Dawley rats along with memory retrieval following exposure to hypobaric
      conditions simulating an altitude of 25,000 ft for different durations. The
      effect of bacoside administration on apoptosis, cytochrome c oxidase activity,
      ATP levels, and oxidative stress markers and on plasma corticosterone levels was
      investigated. Expression of NR1 subunit of N-methyl-d-aspartate receptors,
      neuronal cell adhesion molecules and was also studied along with CREB
      phosphorylation to elucidate the molecular mechanisms of bacoside action.
      Bacoside administration was seen to enhance learning ability in rats along with
      augmentation in memory retrieval and prevention of dendritic atrophy following
      hypoxic exposure. In addition, it decreased oxidative stress, plasma
      corticosterone levels and neuronal degeneration. Bacoside administration also
      increased cytochrome c oxidase activity along with a concomitant increase in ATP
      levels. Hence, administration of bacosides could be a useful therapeutic strategy
      in ameliorating hypobaric hypoxia induced cognitive dysfunctions and other
      related neurological disorders.

PMID- 19154789
TI  - The polymorphism of lysozyme gene in Zhikong scallop (Chlamys farreri) and its
      association with susceptibility/resistance to Listonella anguillarum.
AB  - Lysozyme functions as a crucial biodefence effector against the infection of
      bacterial pathogens in innate immunity. The nucleotide sequence polymorphisms in
      promoter region of a nuclear goose type lysozyme gene from Zhikong scallop
      Chlamys farreri (designated as CFLysG) were investigated to explore their
      association with susceptibility/resistance to Listonella anguillarum infection.
      Eight sites of single nucleotide polymorphisms (SNPs) and two sites of insert
      deletion (ins-del) polymorphisms were identified in the promoter region of
      CFLysG. Two of them, -753 TATCTCGATCAGG ins-del polymorphism and -391 A-G SNP
      were selected to analyze their distribution in the susceptible and resistant
      stocks, which were identified according to the survival time after L. anguillarum
      challenge. Using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP), two genotypes were found at each site, which were
      ins/del and ins/ins at locus -753, and A/A and A/G at locus -391, respectively.
      The -753 ins/del genotype was more prevalent in the resistant stock than that in
      the susceptible stock, 30% vs 16.67% in frequency, but there was no significant
      difference in the frequency distribution between these two stocks (P=0.15). In
      contrast, the frequency of -391A/G genotype in the resistant stock was
      significantly higher (30%) than that in the susceptible stock (7.14%) (P=0.007),
      indicating a significant association with the resistance of Zhikong scallop to L.
      anguillarum. To confirm the presumption, another independent challenge experiment
      was performed, in which the cumulative mortality of scallops with -391 A/A
      genotype (96.8%) was significantly higher than those with -391 A/G genotype
      (64.5%) (P=0.001), which further validate the association between -391 A/G
      genotype and the resistance of Zhikong scallop to L. anguillarum. These results
      suggested that the -391 A/G could be a potential marker applied in future
      selection of Zhikong scallop with enhanced resistance to L. anguillarum.

PMID- 19154790
TI  - Tract-based morphometry for white matter group analysis.
AB  - We introduce an automatic method that we call tract-based morphometry, or TBM,
      for measurement and analysis of diffusion MRI data along white matter fiber
      tracts. Using subject-specific tractography bundle segmentations, we generate an
      arc length parameterization of the bundle with point correspondences across all
      fibers and all subjects, allowing tract-based measurement and analysis. In this
      paper we present a quantitative comparison of fiber coordinate systems from the
      literature and we introduce an improved optimal match method that reduces spatial
      distortion and improves intra- and inter-subject variability of FA measurements.
      We propose a method for generating arc length correspondences across hemispheres,
      enabling a TBM study of interhemispheric diffusion asymmetries in the arcuate
      fasciculus (AF) and cingulum bundle (CB). The results of this study demonstrate
      that TBM can detect differences that may not be found by measuring means of
      scalar invariants in entire tracts, such as the mean diffusivity (MD) differences
      found in AF. We report TBM results of higher fractional anisotropy (FA) in the
      left hemisphere in AF (caused primarily by lower lambda(3), the smallest
      eigenvalue of the diffusion tensor, in the left AF), and higher left hemisphere
      FA in CB (related to higher lambda(1), the largest eigenvalue of the diffusion
      tensor, in the left CB). By mapping the significance levels onto the tractography
      trajectories for each structure, we demonstrate the anatomical locations of the
      interhemispheric differences. The TBM approach brings analysis of DTI data into
      the clinically and neuroanatomically relevant framework of the tract anatomy.

PMID- 19154791
TI  - Combined magnetic resonance and fluorescence imaging of the living mouse brain
      reveals glioma response to chemotherapy.
AB  - Fluorescent molecular tomographic (FMT) imaging can noninvasively monitor
      molecular function in living animals using specific fluorescent probes. However,
      macroscopic imaging methods such as FMT generally exhibit low anatomical details.
      To overcome this, we report a quantitative technique to image both structure and
      function by combining FMT and magnetic resonance (MR) imaging. We show that FMT
      MR imaging can produce three-dimensional, multimodal images of living mouse
      brains allowing for serial monitoring of tumor morphology and protease activity.
      Combined FMT-MR tumor imaging provides a unique in vivo diagnostic parameter,
      protease activity concentration (PAC), which reflects histological changes in
      tumors and is significantly altered by systemic chemotherapy. Alterations in this
      diagnostic parameter are detectable early after chemotherapy and correlate with
      subsequent tumor growth, predicting tumor response to chemotherapy. Our results
      reveal that combined FMT-MR imaging of fluorescent molecular probes could be
      valuable for brain tumor drug development and other neurological and somatic
      imaging applications.

PMID- 19154792
TI  - In vivo cerebromicrovasculatural visualization using 3D DeltaR2-based microscopy
      of magnetic resonance angiography (3DDeltaR2-mMRA).
AB  - This study proposed a novel methodology for depicting cerebral small vessels
      including veins, arterioles, and venules, called 3DDeltaR(2)-mMRA (three
      dimensional, steady-state DeltaR(2)-based, and flow-independent microscopic
      magnetic resonance angiography). The DeltaR(2) map calculated by a fast spin-echo
      imaging technique before and after the injection of an iron-oxide contrast agent
      was used to delineate the relative cerebral blood volume, primarily to
      microvasculature. The proposed 3DDeltaR(2)-mMRA method, which employs 3D
      reconstruction techniques, can simultaneously provide high-resolution 3D
      information on the cerebral anatomy, in vivo microvascular architecture, and
      hemodynamic response, which can be used to evaluate pathological microvascular
      changes over time in cerebromicrovascular disease. Since spin-echo-based
      DeltaR(2) imaging was applied, the inflow effects, susceptibility artifacts, and
      the overestimation of vessel size in brain were reduced. A well-defined three
      vessel occlusion model in the rat was performed to evaluate the capability of the
      proposed method in evaluating alterations to the microvasculature.

PMID- 19154793
TI  - Characterization of Clostridium difficile strains isolated from immunosuppressed
      inpatients in a hospital in Rio de Janeiro, Brazil.
AB  - The aim of this work was to identify and characterize Clostridium difficile
      strains from fecal and hospital environmental samples. C. difficile toxins were
      detected by ELISA in 28.5% of the analyzed samples. Four strains were isolated
      from immunosuppressed inpatients presenting antibiotic-associated diarrhea. All
      strains possessed tcdA and tcdB genes and did not present neither the cdtA and
      cdtB genes nor any significant deletions in the tcdC gene. PFGE and PCR
      ribotyping analysis showed that two strains belonged to the same clonal type
      (ribotype 014) and the other two were grouped into ribotype 106, in spite of
      presenting a similar, but not identical genetic fingerprint. This report shows
      that for the first time ribotype 106 was found outside the United Kingdom. All
      isolates were equally sensitive to metronidazole. The ribotype 014 isolates were
      highly resistant to clindamycin, while the ribotype 106 isolates were resistant
      to all fluoroquinolones tested. This work reveals the spread of C. difficile in
      the hospital unit studied and the presence of three genetically related types,
      two of them presenting resistance to fluoroquinolones.

PMID- 19154794
TI  - ATR (AT mutated Rad3 related) activity stabilizes Cdc6 and delays G2/M-phase
      entry during hydroxyurea-induced S-phase arrest of HeLa cells.
AB  - The Cdc6 protein, a key DNA replication initiation factor, contributes to the
      long-term maintenance of the S-phase checkpoint by anchoring the Rad3-Rad26
      complex to chromatin. Here, we demonstrate that ATR (AT mutated and Rad3 related)
      activity is essential for maintaining high chromatin levels of the Cdc6 protein,
      thereby delaying entry into mitosis during hydroxyurea (HU)-induced S-phase
      arrest of HeLa cells. Downregulation of ATR (AT mutated and Rad3 related) (i.e.,
      using ATR-siRNA) reduced the protein levels of chromatin Cdc6 and significantly
      increased the cellular levels of phospho-histone H3 (Ser 10), an index of
      mitosis. Downregulation of Cdc6 was completely restored by pretreatment with
      MG132, a proteasome inhibitor. Moreover, mitotic entry of MG132-pretreated cells
      was significantly downregulated. Our results also show that ATR (AT mutated and
      Rad3 related) kinase phosphorylates Cdc6 at serine residue 6. Thus, this ATR (AT
      mutated and Rad3 related)-mediated phosphorylation of Cdc6 is likely associated
      with stabilization of Cdc6 protein, thereby maintaining high levels of chromatin
      Cdc6 and delaying premature mitotic entry. This novel mechanism likely
      contributes to the functional regulation of chromatin Cdc6, which delays the cell
      cycle of hydroxyurea-induced cells to enter mitosis at the S-phase checkpoint.

PMID- 19154795
TI  - The Chinese QOLIE-AD-48: translation, validity, and reliability.
AB  - The aim of this study was to translate into Chinese the Quality of Life in
      Epilepsy Inventory for Adolescents (QOLIE-AD-48) and to evaluate its psychometric
      properties. After a multistage translation and cultural adaptation, the final
      Chinese version was administered to 99 adolescents with epilepsy to evaluate its
      validity and reliability. Interitem correlations, correlations with the Pediatric
      Quality of Life Inventory (PedsQL), internal consistency, and sensitivity were
      examined. Mean total score was 66.1, and all subscales contributed significantly
      to the summary measure. Considering the validity of the translation, each item
      correlated more significantly with its own subscale than with the other
      subscales, whereas all subscales were substantially correlated with the PedsQL
      subscales (r=0.73). The internal consistency coefficients of the subscales ranged
      between 0.62 and 0.92, and this coefficient was 0.94 for the total. Finally, the
      QOLIE-AD-48 could detect differences in quality of life between the subjects. In
      conclusion, this study showed that the Chinese QOLIE-AD-48 possesses good
      validity, reliability, and sensitivity, and is an appropriate instrument for
      health-related quality of life assessment in Chinese adolescents with epilepsy.

PMID- 19154796
TI  - Heavy metal and growth hormone pathways in metallothionein regulation in fish RTH
      149 cell line.
AB  - Interference between heavy metals and growth hormone (GH) on cell signaling has
      been previously demonstrated in fish cells. This study was aimed at assessing
      their effects on expression of the metallothionein isoforms MT-A and MT-B. The
      results indicate that all heavy metals induce MT-A more markedly than MT-B, but
      differences appeared when metals were combined with GH. For MT-B induction, a
      positive interference between metals and GH was observed for Zn(2+)/GH and
      Cd(2+)/GH, a negative interference for Hg(2+)/GH. With regards to MT-A, no
      interference was observed for Zn(2+)/GH and Hg(2+)/GH, while a negative
      interference occurred with Cu(2+)/GH and a positive interference with Cd(2+)/GH.
      The possible mechanisms underlying the differential regulation of
      metallothioneins include different signaling pathways. The results show that
      STAT5 and ERKs responded differently to different combinations, and Zn(2+)/GH and
      Cd(2+)/GH exerted a slight positive interference on ERK activation. On the other
      hand, a synergic rise in [Ca(2+)](i) occurred for all combinations except for
      Cu(2+)/GH. Our data suggest that the cross-talk between heavy metals and GH
      resulting in MT transcription modulation does not strictly depend on Ca(2+)
      signalling; (ii)ERK activation may represent the point of cross-talk between
      Zn(2+) or Cd(2+) and GH, converging on MT-B transcription, probably through a
      differential recruitment of transcription factors.

PMID- 19154797
TI  - The caBIG terminology review process.
AB  - The National Cancer Institute (NCI) is developing an integrated biomedical
      informatics infrastructure, the cancer Biomedical Informatics Grid (caBIG), to
      support collaboration within the cancer research community. A key part of the
      caBIG architecture is the establishment of terminology standards for representing
      data. In order to evaluate the suitability of existing controlled terminologies,
      the caBIG Vocabulary and Data Elements Workspace (VCDE WS) working group has
      developed a set of criteria that serve to assess a terminology's structure,
      content, documentation, and editorial process. This paper describes the evolution
      of these criteria and the results of their use in evaluating four standard
      terminologies: the Gene Ontology (GO), the NCI Thesaurus (NCIt), the Common
      Terminology for Adverse Events (known as CTCAE), and the laboratory portion of
      the Logical Objects, Identifiers, Names and Codes (LOINC). The resulting caBIG
      criteria are presented as a matrix that may be applicable to any terminology
      standardization effort.

PMID- 19154798
TI  - Expression patterns of the Egr1 and Egr3 genes during medaka embryonic
      development.
AB  - Egr1 and Egr3 are zinc finger-type transcription factors and known as synaptic
      activity-inducible immediate-early genes. Egr1 also plays important roles in many
      aspects of vertebrate development. Egr3 is known as the gene that is related to
      biological rhythm and muscular development, but its behavior in the central
      nervous system during development is not clear. We cloned the cDNA of the egr1
      and egr3 orthologs in medaka, and examined their expression patterns during
      embryonic development using whole-mount in situ hybridization. Medaka egr3 was
      the first cloned egr3 gene in fish. The expression of egr1 mRNA was first
      detected at 1day post-fertilization (dpf). It was expressed in the whole
      embryonic body. At 3dpf, the egr1 mRNA was strongly expressed in the
      telencephalon, diencephalon, hypothalamus, optic tectum, dorsal medulla
      oblongata, retina, heart, pharynx, and pectoral fin. The expression of egr3 mRNA
      was first detected at 3dpf. It was expressed in the telencephalon, hypothalamus,
      optic tectum, and pharynx. By sectioning the whole-mount specimens, expression of
      both the egr1 and egr3 mRNAs were observed in the telencephalon, hypothalamus,
      and optic tectum. However, the positions at which the genes were expressed were
      different.

PMID- 19154799
TI  - Inverse relationship between longevity and evolutionary rate of mitochondrial
      proteins in mammals and birds.
AB  - Recently, an unexpected, positive correlation between the rate of evolution of
      mitochondrial proteins and longevity was reported. Here we re-analyze this
      relationship in various mammalian lineages using a bayesian phylogenetic analysis
      of amino-acid sequences, allowing for variable evolutionary rates across sites
      and species. A negative relationship between protein evolutionary rate and
      species longevity is reported for all oxidative phosphorylation complexes. A
      detailed analysis of the cytochrome b in 528 mammals reinforced this result,
      which contradicts previous publications. Reconducting the analysis in birds
      yielded similar results. We explain the discrepancy between this and previous
      reports by our improved taxon sampling and more appropriate methodology: unlike
      distance-based methods, the tree-based bayesian approach can take into account
      the high variation of substitution rate across amino-acid sites, and the
      resulting multiple substitution events. We discuss how our analysis contradicts
      Rottenberg's rationale, but does not dismiss his proposal of a longevity
      dependent selective pressure on mitochondrial mutation rate in mammals and birds.
      This is because his interpretation invokes adaptation as the single evolutionary
      force at work, disregarding the effects of mutation, genetic drift, and purifying
      selection.

PMID- 19154800
TI  - Respiratory response to systemic inhibition of the Na+/H+ exchanger type 3 in
      intact rats.
AB  - The Na+/H+ exchangers (NHEs) are a family of antiporters involved in the
      maintenance of neural steady-state intracellular pH. The NHE3 seems to be the
      predominant subtype in central chemosensitive cells. We aimed to analyze the
      effect of a selective NHE3 inhibition on the respiratory pattern in spontaneously
      breathing rats with intact vagi. Rats were intravenously infused for 10 min with
      the selective NHE3 inhibitor AVE1599 (Aventis Pharma Deustchland, 0.5 and 2
      mg/kg) or with phosphate buffer. Whole-body plethysmography was used to monitor
      breathing pattern before, during, and up to 30 min after the drug infusion.
      Immunohistochemistry for the c-Fos protein was performed in the animal brains and
      c-Fos-positive cells were counted along the brainstem. Selective NHE3 inhibition
      induced a significant increase in the respiratory frequency and in the number of
      c-Fos immunopositive cells in the lateral parabrachial nucleus, the pre-Botzinger
      complex and a rostral extension of the retrotrapezoid nucleus/parapyramidal
      region (p<0.05, ANOVA). We conclude that systemic administration of AVE1599
      increases respiratory frequency and activates ponto-medullary areas implicated in
      the central control of breathing and chemoreception.

PMID- 19154801
TI  - Comparing standard and microwave assisted staining protocols for SDS-PAGE of
      glycoproteins followed by subsequent PMF with MALDI MS.
AB  - The detection of glycoproteins on SDS-PAGE gels is a very challenging task as
      glycan moieties can inhibit the protein-dye interaction or protein-silver
      reaction slowing down or even completely preventing the staining process.
      Additionally the applied staining procedure can influence the total number of
      detected peptides after in-gel digestion. Three in SDS-PAGE commonly used
      staining procedures (silver nitrate, CBB R250 and colloidal CBB G250) were
      evaluated in terms of duration, sensitivity and obtainable sequence coverage
      after PMF. The staining procedures were performed with and without the assistance
      of microwave irradiation. Microwave treatment resulted in comparable band
      intensities and sensitivities as obtained by the original staining protocols
      (limit of detection for microwave assisted silver staining: 50 ng), but staining
      duration was significantly reduced, to 30 min for silver nitrate and to 1.5 h for
      CBB and cCBB staining method. PMF analysis by MALDI mass spectrometry was not
      affected by the microwave treatment. It was found that the total number of
      detected tryptic peptides has increased when applying microwave irradiation
      during the staining process (average sequence coverage 31-56% and 76% for
      Avidin).

PMID- 19154802
TI  - Effect of oral erythromycin therapy in patients with aseptic loosening of joint
      prostheses.
AB  - There is currently no cure for aseptic loosening (AL) of total joint replacement
      (TJR) except surgical revision. The purpose of this study was to determine
      whether oral EM could improve the periprosthetic tissue profiles and reduce serum
      cytokine production in AL patients who are candidates for surgical revision. We
      recruited 32 AL patients. AL patients were treated with either EM (600 mg/day,
      n=18) or placebo (n=14) daily, started one month before surgery and ending on the
      day of surgery. Blood samples were obtained before EM treatment and during
      surgery. Periprosthetic tissues and joint fluids were collected during surgery.
      Our results demonstrate that oral EM reduces the inflammation of periprosthetic
      tissues, as manifested by the reduction of the numbers of infiltrating cells,
      CD68+ macrophages, RANKL+ cells, and TRAP+ cells. Remarkable decreases of
      TNFalpha (9.6-fold), IL-1beta (21.2-fold), and RANKL (76-fold) gene transcripts
      were observed in periprosthetic tissues of patients treated with oral EM. Serum
      levels of both TNFalpha and (to a lesser extent) IL-1beta were significantly
      reduced following EM treatment (p<0.05). Our results suggest that EM represents a
      biological cure or prevention for those patients who might need repeated revision
      surgeries and/or show the early signs of progressive osteolysis after TJR.

PMID- 19154803
TI  - The potential of mass spectrometry to study iron-containing proteins used in
      clinical diagnosis.
AB  - Many proteins contain iron as metal ion either within their own structures or
      bound to their active sites. These iron-containing proteins are involved in
      numerous biological processes and some of them serve as biomarkers of clinical
      pathologies, not only related to iron homeostasis but also to other physiological
      disorders. Thus, a variety of analytical strategies have been developed over the
      last years in order to conduct studies on Fe-containing proteins. Among them,
      mass spectrometric (MS) methods still remain as preferred tools since they
      provide the capabilities of structure elucidation together with quantitative
      possibilities. Therefore, in this work we have tried to summarize the most recent
      applications of elemental and molecular mass spectrometric-based methods for the
      characterization (mostly qualitative but quantitative in some cases) of the high
      abundant Fe-containing proteins used for clinical diagnosis.

PMID- 19154804
TI  - Hollow fiber liquid phase microextraction combined with electrothermal atomic
      absorption spectrometry for the speciation of arsenic (III) and arsenic (V) in
      fresh waters and human hair extracts.
AB  - A new method of hollow fiber liquid phase microextraction (HF-LPME) using
      ammonium pyrrolidine dithiocarbamate (APDC) as extractant combined with
      electrothermal atomic absorption spectrometry (ETAAS) using Pd as permanent
      modifier has been described for the speciation of As(III) and As(V). In a pH
      range of 3.0-4.0, the complex of As(III)-APDC complex can be extracted using
      toluene as the extraction solvent leaving As(V) in the aqueous layer. The post
      extraction organic phase was directly injected into ETAAS for the determination
      of As(III). To determine total arsenic in the samples, first As(V) was reduced to
      As(III) by l-cysteine, and then a microextraction method was performed prior to
      the determination of total arsenic. As(V) assay was based on subtracting As(III)
      form the total arsenic. All parameters, such as pH of solution, type of organic
      solvent, the amount of APDC, stirring rate and extraction time, affecting the
      separation of As(III) from As(V) and the extraction efficiency of As(III) were
      investigated, and the optimized extraction conditions were established. Under
      optimized conditions, a detection limit of 0.12ngmL(-1) with enrichment factor of
      78 was achieved. The relative standard deviation (R.S.D.) of the method for five
      replicate determinations of 5ngmL(-1) As(III) was 8%. The developed method was
      applied to the speciation of As(III) and As(V) in fresh water and human hair
      extracts, and the recoveries for the spiked samples are 86-109%. In order to
      validate the developed method, three certified reference materials such as
      GBW07601 human hair, BW3209 and BW3210 environmental water were analyzed, and the
      results obtained were in good agreement with the certified values provided.

PMID- 19154805
TI  - Overcoming interference from the alumina matrix on the determination of arsenic
      at 189 nanometers using electrothermal atomic absorption spectrometry.
AB  - A method is described enabling to eliminate the spectral interference from
      alumina matrix onto As determination at the wavelength 189 nm by electrothermal
      atomic absorption spectrometry with deuterium background correction. Matrix
      modification was performed by the addition of ammonium fluoride to protect the
      formation of aluminium oxide implicated in causing spectral interference and to
      increase volatility of alumina matrix via the formation of AlF(3). Pre-treating
      of the pyrolytic graphite platform with a solution of rhodium and citric acid has
      enabled to stabilize the analyte up to temperature of 1300 degrees C at which
      most of AlF(3) could be removed from the graphite furnace. The application of 2
      microg of Rh+20 microg of citric acid+200 microg of NH(4)F has enabled an
      accurate and interference-free determination of As up to 40 microg of Al in the
      form of AlCl(3) as verified by analytical recoveries study and resulted in
      characteristic mass and LOD value in the original sample 15 pg and 50 ngg(-1),
      respectively (10-microL aliquots of sample).

PMID- 19154806
TI  - QSPR models for half-wave reduction potential of steroids: a comparative study
      between feature selection and feature extraction from subsets of or entire set of
      descriptors.
AB  - Steroids are widely distributed in nature and are found in plants, animals, and
      fungi in abundance. A data set consists of a diverse set of steroids have been
      used to develop quantitative structure-electrochemistry relationship (QSER)
      models for their half-wave reduction potential. Modeling was established by means
      of multiple linear regression (MLR) and principle component regression (PCR)
      analyses. In MLR analysis, the QSPR models were constructed by first grouping
      descriptors and then stepwise selection of variables from each group (MLR1) and
      stepwise selection of predictor variables from the pool of all calculated
      descriptors (MLR2). Similar procedure was used in PCR analysis so that the
      principal components (or features) were extracted from different group of
      descriptors (PCR1) and from entire set of descriptors (PCR2). The resulted models
      were evaluated using cross-validation, chance correlation, application to
      prediction reduction potential of some test samples and accessing applicability
      domain. Both MLR approaches represented accurate results however the QSPR model
      found by MLR1 was statistically more significant. PCR1 approach produced a model
      as accurate as MLR approaches whereas less accurate results were obtained by PCR2
      approach. In overall, the correlation coefficients of cross-validation and
      prediction of the QSPR models resulted from MLR1, MLR2 and PCR1 approaches were
      higher than 90%, which show the high ability of the models to predict reduction
      potential of the studied steroids.

PMID- 19154807
TI  - Nano level detection of Cd(II) using poly(vinyl chloride) based membranes of
      Schiff bases.
AB  - The construction and performance characteristics of polymeric membrane electrodes
      based on two neutral ionophores, 2,2'-(1Z,1'Z)-(1E,1'E)-(1,2-phenylenebis(methan
      1-yl-1-ylidene))bis(azaan-1-yl-1-ylidene)bis(methylene)bis(azan-1-yl-1
      ylidene)bis(methan-1-yl-ylidene)diphenol (L(1)) and 4,4'-(1E,1'E)-(butane-1,4
      diylbis(azan-1-yl-1-ylidene))bis(methan-1-yl-1-ylidene)dinaphthalen-1-ol (L(2))
      for quantification of cadmium ions, are described. The influences of membrane
      compositions on the potentiometric response of the electrodes have been found to
      substantially improve the performance characteristics. The best performance was
      obtained with the electrode having a membrane composition (w/w) of (L(1))
      (2.6%):PVC (31.6%):DOP (63.2%):NaTPB (2.6%). The proposed electrode exhibits
      Nernstian response in the concentration range 5.0 x 10(-9) to 1.0 x 10(-1)M
      Cd(2+) with limit of detection 3.1 x 10(-9), performs satisfactorily over wide pH
      range (2.0-8.5) with a fast response time (11s). The electrode has been found to
      work satisfactorily in partially non-aqueous media up to 40% (v/v) content of
      methanol, ethanol and acetonitrile and could be used for a period of 2.5 months.
      The analytical usefulness of the proposed electrode has been evaluated by its
      application in the determination of cadmium in cigarette samples. The practical
      utility of the membrane electrode has also been observed in the presence of
      surfactants.

PMID- 19154808
TI  - Label-free monitoring of site-specific DNA cleavage by EcoRI endonuclease using
      cyclic voltammetry and electrochemical impedance.
AB  - Cyclic voltammetry (CV) combined with electrochemical impedance spectroscopy
      (EIS) were proposed to monitor the site-specific DNA cleavage by EcoRI
      endonuclease without using external label. The alteration of CV and EIS signal
      demonstrated that double-strands (dsDNA) contain recognition sequence was cleaved
      by EcoRI endonuclease. Real-time monitoring indicated that the dsDNA was cleaved
      by EcoRI more than 90% after 2h of enzyme digestion time. Control experiment
      showed that the DNA cleavage by EcoRI endonuclease is site-specific for DNA
      sequence. Experimental results demonstrated that the efficiency of EcoRI cleavage
      was highly dependent on the concentration of EcoRI concentration in the range
      from 0.04 to 0.4UmuL(-1) with one almost linear relationship.

PMID- 19154809
TI  - A detailed investigation for determination of tannic acid by anodic stripping
      voltammetry using porous electrochemical sensor.
AB  - The electrochemical responses of tannic acid have been obtained at porous pseudo
      carbon paste electrode (PPCPE), polypyrrole modified carbon paste electrode
      (PCPE), SBA-15 modified CPE (SBA-MCPE) and carbon paste electrode (CPE) under
      same conditions, respectively. The results show that the sensitivity of PPCPE is
      the highest among all the checked electrodes. The detection limit at PPCPE is
      0.01 microM, which is about 10 times lower than that at CPE and is about 5 times
      lower than that at PCPE or SBA-MCPE. The developed electrode PPCPE possesses a
      few obvious advantages and no binding reagents are needed. The surface area of
      PPCPE is 59.26 m(2)g(-1) with pores ranging from 2 to 5 microm in diameter. The
      PPCPE is easy to preserve and has good reusability, which affords a nice
      electrochemical platform for detecting tannic acid.

PMID- 19154810
TI  - Rapid Folin-Ciocalteu method using microtiter 96-well plate cartridges for solid
      phase extraction to assess urinary total phenolic compounds, as a biomarker of
      total polyphenols intake.
AB  - Nutritional markers have several advantages for epidemiologic and clinical
      assays, when compared to dietary data obtained by food frequency questionnaires.
      Few studies have assessed whether total polyphenol (TP) compounds provide a valid
      biomarker for TP intake. To date, there has been almost no literature describing
      methods to determine TP in complex matrices such as urine, which have many
      interfering substances. We report a rapid Folin-Ciocalteu method to determine TP
      in urine samples using Oasis((R)) MAX 96-well plate cartridges for solid phase
      extraction. These plates allow analysis of a high number of samples at the same
      time. We performed a prospective, randomized, crossover trial and one cross
      sectional study with 60 volunteers from the PREDIMED trial, seeking to evaluate
      whether the TP in urine were correlated with polyphenol intake and could,
      therefore, be considered as a marker of intake of these compounds. The assay was
      optimized; the sensitivity and the polarity range of urine polyphenols were
      increased and the detection and quantification limits were significantly reduced.
      The metabolites in standards solution and urine samples were stable under the
      storage and handling conditions. In the clinical trial and the cross-sectional
      study, TP excreted in spot urine samples were positively correlated with TP
      intake, r=0.48, P<0.01 and r=0.257, P=0.04, respectively. The methodology
      described may be used to detect TP in urine samples, employing the high
      throughput of 96-well microtiter plates and reader. The method is fast and simple
      and it allows analysis of a large number of samples at the same time.

PMID- 19154811
TI  - Microfluidic pool structure for cell docking and rapid mixing.
AB  - A microfluidic pool structure for cell docking and rapid mixing is described. The
      pool structure is defined as a microchamber on one structural layer of a bilayer
      chip and connects with two or more individual microchannels on the other
      structural layer. In contrast to the turbulent flow in a macroscale pool, laminar
      streams enter and exit this microfluidic pool structure with definite and
      controllable direction that may be influenced by the location and geometry of the
      pool. A simple microfluidic model was used to validate this hypothesis. In this
      model, a microscale pool structure was made on the lower layer of a chip and
      connected with three parallel microchannels in the upper layer. Simulation and
      experimental results indicated that the flow profile within the pool structure
      was determined by its geometry and location. This could be used as a flow control
      method and it was simpler than designs based on microvalve, hydraulic pressure,
      or electrokinetic force, and has some important applications. For example,
      controllable streams within this structure were used to immobilize biological
      cells along the microchannel walls. When different solution streams flowed
      through the pool, rapid diffusion of analytes occurred for short diffusion
      distance between vertical flow laminas. Furthermore, desired dilution (mixing)
      ratio could be obtained by controlling the geometry of the microfluidic pool.

PMID- 19154812
TI  - Chromium(III) determination without sample treatment by batch and flow injection
      potentiometry.
AB  - A new and easy device for direct detection of chromium(III) in batch and flow
      analysis without previous oxidation/reduction or preconcentration steps of
      samples is designed and evaluated. For this purpose a potentiometric sensor with
      solid state membrane based on carbon paste matrix is developed. The sensor is
      modified with di(2-hydroxyphenylimino)ethane and the principal analytical
      parameters of the potentiometric response in batch and flow analysis are
      optimized and calculated. Optimal detection limits (1.4 x 10(-7)M in static mode
      and 5.4 x 10(-7)M in on-line analysis) and selectivity to trivalent chromium are
      obtained in both analysis modes. The use of this device to direct detection of
      chromium(III) in real samples is tested using a sediment Certified Reference
      Material. Chromium(III) determination is also carried out with successful results
      in environmental samples such as extracts from soils used as barriers in
      landfills and industrial samples such as waste waters from electroplating
      industries.

PMID- 19154813
TI  - Evaluation of stable isotope labelling strategies for the quantitation of CP4
      EPSPS in genetically modified soya.
AB  - The introduction of genetically modified (GM) crops into the market has raised a
      general alertness relating to the control and safety of foods. The applicability
      of protein separation hyphenated to mass spectrometry to identify the bacterial
      enolpyruvylshikimate-3-phosphate synthase (CP4 EPSPS) protein expressed in GM
      crops has been previously reported [M.F. Ocana, P.D. Fraser, R.K.P. Patel, J.M.
      Halket, P.M. Bramley, Rapid Commun. Mass Spectrom. 21 (2007) 319.]. Herein, we
      investigate the suitability of two strategies that employ heavy stable isotopes,
      i.e. AQUA and iTRAQ, to quantify different levels of CP4 EPSPS in up to four GM
      preparations. Both quantification strategies showed potential to determine
      whether the presence of GM material is above the limits established by the
      European Union. The AQUA quantification procedure involved protein
      solubilisation/fractionation and subsequent separation using SDS-PAGE. A segment
      of the gel in which the protein of interest was located was excised, the stable
      isotope labeled peptide added at a known concentration and proteolytic digestion
      initiated. Following recovery of the peptides, on-line separation and detection
      using LC-MS was carried out. A similar approach was used for the iTRAQ workflow
      with the exception that proteins were digested in solution and generated tryptic
      peptides were chemically tagged. Both procedures demonstrated the potential for
      quantitative detection at 0.5% (w/w) GM soya which is a level below the current
      European Union's threshold for food-labelling. In this context, a comparison
      between the two procedures is provided within the present study.

PMID- 19154814
TI  - Quantitative detection of antibody based on single-molecule counting by total
      internal reflection fluorescence microscopy with quantum dot labeling.
AB  - We presented a sensitive method to quantify antibody based on single-molecule
      counting by total internal reflection fluorescence microscopy with quantum dot
      labeling. In this method, the biotinylated monoclonal anti-human IgG molecules
      were immobilized on the silanized glass substrate surface. By the strong biotin
      streptavidin affinity, streptavidin-coated quantum dots were labeled to the
      target molecules as fluorescent probe. Then, images of fluorescent spots in the
      evanescent wave field were obtained by a high-sensitivity electron multiplying
      charge-coupled device. Finally, the number of fluorescent spots corresponding to
      single molecules in the subframe images was counted, one by one. The linear range
      of 8.0 x 10(-14) to 5.0 x 10(-12)molL(-1) was obtained between the number of
      single molecules and the sample concentration.

PMID- 19154815
TI  - Development of enzyme-based bar code-style lateral-flow assay for hydrogen
      peroxide determination.
AB  - A unique approach of developing a bar code version of lateral-flow enzymatic
      based assay for the semi-quantification of hydrogen peroxide is described. The
      proposed assay system is mainly composed of a goat anti-mouse IgG-horseradish
      peroxidase conjugate (Gt anti-M IgG-HRP)-coated nitrocellulose (NC) membrane and
      a peroxidase substrate pad. Unlike the bar code immunochromatographic assay which
      depends on the stepwise capture of analyte, the principle of enzyme-based bar
      code lateral-flow assay is based on the different reaction time on successive
      lines due to the delay in 3,3',5,5'-tetramethylbenzidine (TMB) release. Hydrogen
      peroxide (H(2)O(2)) acts as a limiting factor which controls the rate of the
      enzymatic conversion of TMB to blue color complex. The system expresses the
      concentration of H(2)O(2) in micromole range as three distinct ladder bars in 9
      min therefore without the need of any reading device. The major advantages of
      this assay are its easily readable result, and also its simplicity and low-cost
      in production offers a cheaper alternative for testing those expensive biosensors
      might not be available to the third world countries. By incorporating with
      H(2)O(2)-generating oxidoreductases, the assay can be further extended to detect
      a variety of analytes with clinical and environmental importance. Glucose was
      chosen to be the model analyte where the proposed system gave signal response at
      between 5 microM and 100 microM.

PMID- 19154816
TI  - Activated aluminum oxide selectively retaining long chain n-alkanes. Part I,
      description of the retention properties.
AB  - Aluminum oxide activated by heating to 350-400 degrees C retains n-alkanes with
      more than about 20 carbon atoms, whereas iso-alkanes largely pass the column non
      retained. Retention of n-alkanes is strong with n-pentane or n-hexane as mobile
      phase, but weak or negligible with cyclohexane or iso-octane. It is strongly
      reduced with increasing column temperature. Even small amounts of polar
      components, such as modifiers or impurities in the mobile phase, cause the
      retention of n-alkanes to irreversibly collapse. Since n-alkanes are not more
      polar than iso-alkanes and long chain n-alkanes not more polar than those of
      shorter chains, retention by a mechanism based on steric properties is assumed.
      The sensitivity to deactivation by polar components indicates that polar
      components and n-alkanes are retained by the same sites. The capacity for
      retaining n-alkanes is low, with the effect that the retention of n-alkanes
      depends on the load with retained paraffins. These retention properties are
      useful for the pre-separation of hydrocarbons in the context of the analysis of
      mineral oil paraffins in foodstuffs and tissue, where plant n-alkanes, typically
      ranging from C(23) to C(33), may severely disturb the analysis (subject of Part
      II).

PMID- 19154817
TI  - Activated aluminum oxide selectively retaining long chain n-alkanes: Part II.
      Integration into an on-line high performance liquid chromatography-liquid
      chromatography-gas chromatography-flame ionization detection method to remove
      plant paraffins for the determination of mineral paraffins in foods and
      environmental samples.
AB  - Aluminum oxide activated by heating to 300-400 degrees C retains n-alkanes with
      more than about 20 carbon atoms, whereas iso-alkanes largely pass non-retained
      (with characteristics described in more detail in Part I). This property is
      useful for the analysis of mineral oil contamination of foods and other matrices:
      it enables the removal of plant n-alkanes, typically ranging from C(23) to C(33),
      when they disturb the analysis of mineral paraffins (usually almost exclusively
      consisting of iso-alkanes). An on-line HPLC-LC-GC-FID method is proposed in which
      a first silica gel HPLC column isolates the paraffins from the bulk of edible
      oils or extracts and is backflushed with dichloromethane. In a second separation
      step, a 10 cm x 2 mm i.d. column packed with activated aluminum oxide separates
      the long chain n-alkanes from the fraction of the iso-alkanes which is
      transferred to GC-FID by the on-column interface and the retention gap technique.
      The retained n-alkanes are removed by flushing with iso-octane.

PMID- 19154818
TI  - High-performance liquid chromatographic analysis of amphotericin B in rat plasma
      using alpha-naphthol as an internal standard.
AB  - A simple, sensitive and accurate reverse phase high-performance liquid
      chromatographic (RP-HPLC) method with photo-diode array detector (PDA) was
      developed and validated for the determination of amphotericin B (AMB) in the rat
      plasma using a new internal standard (IS) alpha-naphthol. The plasma samples were
      subjected to protein precipitation with methanol prior to a HPLC analysis.
      Chromatographic separations were achieved on a Nucleosil 100-5C18 (150 mm x 4.6
      mm) column. The mobile phase consisted of acetonitrile and sodium acetate buffer
      (pH 4; 10mM) in a gradient mode. Detection was carried out at a wavelength of 407
      and 294 nm for AMB and IS, respectively. The retention times of AMB and IS were
      about 6.8 and 7.8 min, respectively. The calibration curve was linear in the
      range of 10-2000 ngmL(-1) for AMB (r(2)>0.998). No significant matrix effect was
      observed on quantification of AMB or IS. At three quality control concentrations
      of 20, 500, and 2000 ngmL(-1), the intra-day and inter-day relative standard
      deviation ranged from 1.13% to 4.91%. The limit of detection (LOD) was 5 ngmL(-1)
      and the limit of quantification (LOQ) was 10 ngmL(-1) for AMB in rat plasma. This
      method is simple, sensitive, rapid and does not require any extensive sample
      purification before injecting into HPLC.

PMID- 19154819
TI  - An investigation of bioactive phytochemicals in the leaves of Melicope vitiflora
      by electrospray ionisation ion trap mass spectrometry.
AB  - The ethyl acetate extract of the leaves of Melicope vitiflora was separated by
      column chromatography and the resulting fractions tested for their bioactivity
      towards methicillin-resistant-Staphylococcus aureus (MRSA) and Micrococcus luteus
      (ML). The bioactive column chromatography fractions were further separated by
      preparative TLC and dereplication was carried out on them by first subjecting
      them to electrospray ionisation-ion trap mass spectrometry (ESI-MS(n)). The
      resulting molecular masses, their fragmentation patterns in addition to the
      chemnet database (www.chemnetbase.com) were used to aid in the structural
      elucidation of some of the compounds by permitting comparison with known
      structures of natural origin. Some molecular masses and the corresponding
      fragmentations were found that did not correlate with any known compounds thus
      revealing potentially novel natural products that could be investigated on a
      larger scale and could ultimately find application as new drugs against MRSA and
      other multi drug resistant microorganisms. Structures are also proposed for known
      compounds that have not been previously reported for M. vitiflora.

PMID- 19154820
TI  - Simple spectrophotometric assessment of the trans-/cis-resveratrol ratio in
      aqueous solutions.
AB  - The solubility and molar absorptivity of trans- and cis-resveratrol isomers in
      aqueous solvents are poorly described. This study aimed to develop and describe a
      new simple method for the determination of trans- and cis-resveratrol
      concentrations in aqueous solutions. Up to 300 microM trans-resveratrol was
      dissolved in water by sonication for 2h. Cis-resveratrol was obtained by exposing
      a 100-muM trans-resveratrol aqueous solution to sunlight for 8h, followed by HPLC
      separation and analysis by mass spectrometry (resveratrol oxidation products were
      absent). Accurate values for UV absorbance in water were [see text], epsilon(286
      nm)=23400 M(-1)cm(-1) for trans-resveratrol and [see text], epsilon(304nm)=9515
      M(-1)cm(-1) for cis-resveratrol. These values allowed us to propose formulae to
      assess the trans-/cis-resveratrol ratio in water, using a simple and reliable UV
      vis spectrophotometric method. Statistical analysis revealed no significant
      difference between our UV method and the commonly used HPLC method. All these
      data are transferable to 150 mM NaCl and 10 mM phosphate buffer solutions, which
      could be particularly useful for cell culture, ex vivo and in vivo studies.

PMID- 19154821
TI  - Development and validation of an immunochromatographic assay for rapid multi
      residues detection of cephems in milk.
AB  - A one-step immunochromatographic assay (ICA) was developed for the detection of
      seven kinds of cephems in milk. Polyclonal antibodies (PcAb) with group-specific
      to cephems were raised in rabbits after immunization with cephalexin-keyhole
      limpet hemocyanin (KLH) conjugate. The specificity of anti-sera was determined by
      indirect competitive enzyme-linked immunosorbent assay (icELISA), and the 50%
      inhibitions (IC(50)) of cephalexin and cefadroxil were obtained at 1.5 ngmL(-1);
      IC(50) of cefatiofur, cefapirin, cefazolin, cefalothin and cefotaxine were 4,
      3.7, 3.2, 4.5 and 5 ngmL(-1), respectively. The PcAb against cephems were
      conjugated to colloidal gold particles as the detection reagent for ICA strips to
      test for cephems. This method achieved semi-quantitative detection of cephems in
      <5 min, with high sensitivity to cephalexin and cefadroxil (both 0.5 ngmL(-1)).
      At the same time, cefatiofur, cefapirin, cefazolin, cefalothin and cefotaxine
      were detected at <100 ngmL(-1) in spiked processed-milk samples. This method was
      compared with an enzyme-linked immunosorbent assay by testing 40 milk samples,
      and the positive samples were validated by a high-performance liquid
      chromatographic method, with an agreement rate of 100% for both comparisons. In
      conclusion, the method was rapid and accurate for the multi-residue detection of
      cephems in milk.

PMID- 19154822
TI  - Sensorimotor deficits remain despite resolution of symptoms using conservative
      treatment in patients with tennis elbow: a randomized controlled trial.
AB  - OBJECTIVES: To evaluate the time course of sensorimotor deficits in lateral
      epicondylalgia (LE; tennis elbow) and how these deficits may be influenced by
      common conservative treatments. DESIGN: Single-blind randomized controlled trial.
      SETTING: University laboratory, Australia. PARTICIPANTS: A total of 198
      participants with unilateral LE of a minimum 6 weeks duration and normative data
      from a group of 40 healthy participants. INTERVENTIONS: Participants with LE were
      randomly assigned to physical therapy, corticosteroid injection, or a wait-and
      see approach with ergonomic advice. MAIN OUTCOME MEASURES: Upper-limb reaction
      time (simple, 1-choice and 2-choice reaction time) and speed of movement were
      assessed at baseline and 6 and 52 weeks of follow-up. RESULTS: Patients with LE
      exhibited delayed reaction times (P<.001) and slower movement speeds (P<.001) for
      both the affected and unaffected arm at baseline, compared with normative data.
      Despite some improvement over time, significant bilateral deficits remained
      compared with healthy participants, with no significant differences between the
      affected and unaffected arm. Overall, there was no significant difference between
      the 3 treatment groups over time. CONCLUSIONS: Sensorimotor deficits remain
      relatively unchanged over time and are present bilaterally in patients with
      unilateral LE. Treatment did not influence the time course of the sensorimotor
      deficits. This prompts conjecture as to the relationship and clinical relevance
      of sensorimotor deficits in LE. It should be noted that treatment evaluated in
      this study did not specifically target sensorimotor function, and further
      investigation into the significance of sensorimotor deficits in patients with LE
      is required.

PMID- 19154823
TI  - Botulinum toxin dilution and endplate targeting in spasticity: a double-blind
      controlled study.
AB  - OBJECTIVE: To determine the effects of botulinum neurotoxin type A (BTX-A)
      dilution and endplate-targeting in spastic elbow flexors. DESIGN: Double blind
      randomized controlled trial; 4-month follow-up after a 160-unit injection of BTX
      A into spastic biceps brachii (4 sites). Randomization into: group 1: 100 mouse
      units (MU)/mL dilution, 0.4cc/site, 4-quadrant injection; group 2: 100MU/mL
      dilution, 0.4cc/site, 4 sites along endplate band; group 3: 20MU/mL dilution,
      2cc/site, 4-quadrant injection (n=7 per group). SETTING: Institutional tertiary
      care ambulatory clinic. PARTICIPANTS: Referred sample of 21 adults with spastic
      hemiparesis. No participant withdrew due to adverse effects. INTERVENTION: A 160
      unit injection of BTX-A of different dilutions and locations into biceps brachii.
      MAIN OUTCOME MEASURES: Primary: agonist and antagonist (cocontraction) mean
      rectified voltage (MRV) of elbow flexors/extensors during maximal isometric
      flexion/extension; secondary: maximal voluntary power of elbow flexion/extension;
      spasticity angle and grade in elbow flexors/extensors (Tardieu Scale); active
      range of elbow extension/flexion. RESULTS: BTX-A injection overall reduced
      agonist flexor MRV (-47.5%, P<0.0001), antagonist flexor MRV (-12%, P=.037),
      antagonist extensor MRV (-19%, P<.01), flexion maximal voluntary power (-33%,
      P<.001), elbow flexor spasticity angle (-30%, P<.001) and grade (-17%, P=.03),
      and increased extension maximal voluntary power (24%, P=.037) and active range of
      elbow extension (5.5%, 8 degrees , P=.002). Agonist and antagonist flexor MRV
      reductions in group 3 (-81% and -31%) were greater than in groups 1 and 2,
      whereas increase in active range of elbow extension was greater in group 2 (10%)
      than in groups 1 and 3 (P<.05, analysis of covariance [ANCOVA]). Elbow flexor
      spasticity was significantly reduced in groups 2 and 3 only (P<.05, ANCOVA).
      CONCLUSIONS: In spastic biceps, high-volume or endplate-targeted BTX-A injections
      achieve greater neuromuscular blockade, cocontraction and spasticity reduction,
      and active range of elbow extension improvement, than low volume, nontargeted
      injections.

PMID- 19154824
TI  - Classification schema of posttraumatic amnesia duration-based injury severity
      relative to 1-year outcome: analysis of individuals with moderate and severe
      traumatic brain injury.
AB  - OBJECTIVE: Early investigations classified traumatic brain injury (TBI) severity
      according to posttraumatic amnesia (PTA) duration, designating "greater than 7
      days" as the most severe. PTA durations of more than 7 days are common in
      neurorehabilitation populations. Moreover, no study has derived a PTA severity
      schema anchored to late outcome. The purpose of this study was to develop a PTA
      severity classification schema. DESIGN: Prospective observational study. SETTING:
      Rehabilitation hospital. PARTICIPANTS: Sample included TBI Model System
      participants (N=280) with known or imputed PTA duration during acute
      hospitalization and 1-year productivity status. Participants were primarily male
      (70%), median age of 27 years; and the most common mechanism of injury was motor
      vehicle collisions (79%). For study purposes, 4 injury severity groups were
      identified by observing differences in productivity associated with different PTA
      durations. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Productivity status at 1
      year postinjury. RESULTS: Fisher exact test comparisons revealed significant
      differences among 3 of the groups. Most individuals with PTA fewer than 14 days
      had favorable 1-year outcome (68% productive), whereas worse outcomes were
      associated with PTA more than 28 days (18% productive). CONCLUSIONS: If validated
      by other investigators, the proposed schema will be useful in determining
      prognosis for late functional status based on PTA duration.

PMID- 19154825
TI  - Redefining the manual wheelchair stroke cycle: identification and impact of
      nonpropulsive pushrim contact.
AB  - OBJECTIVES: To create a comprehensive definition of the manual wheelchair stroke
      cycle, which includes multiple periods of pushrim contact, and to show its
      improved clinical benefit to wheelchair propulsion analyses. DESIGN: Cross
      sectional biomechanics study. SETTING: Three motion analysis laboratories.
      PARTICIPANTS: Persons (N=54) with paraplegia who use a manual wheelchair.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Pushrim forces, axle
      moments, and contact angles measured during wheelchair propulsion. RESULTS: Total
      force on the pushrim was used to define pushrim contact and positive axle moment
      was used to identify the included period of propulsive contact. During most
      strokes, periods of nonpropulsive contact existed before and after propulsive
      contact. Within these periods, braking moments were applied to the pushrim,
      resulting in negative power output, or power loss. Including nonpropulsive data
      decreased mean stroke moment and power. The magnitude and the angle over which
      braking moments and power loss occurred increased with wheel speed. Mean braking
      moment and power loss within the initial contact period were significantly
      (P<.001) related to stroke pattern. CONCLUSIONS: The proposed definition of the
      stroke cycle provides a thorough and practical description of wheelchair
      propulsion. Researchers and clinicians should use this definition to understand
      and minimize the impact of nonpropulsive contact throughout the stroke.

PMID- 19154826
TI  - The impact of adaptive seating devices on the lives of young children with
      cerebral palsy and their families.
AB  - OBJECTIVE: To determine the parent-perceived effect of adaptive seating devices
      on the lives of young children with cerebral palsy (CP) (aged 2-7y) and their
      families. DESIGN: Baseline-intervention-baseline study. SETTING: Homes of
      participating families. PARTICIPANTS: Thirty parents and their children with
      Gross Motor Function Classification System level III or IV CP. INTERVENTIONS: Two
      special-purpose seating devices: 1 for sitting support on the floor or on a chair
      and the other for postural control on a toilet. MAIN OUTCOME MEASURES: Family
      Impact of Assistive Technology Scale (FIATS) and Impact on Family Scale (IFS).
      RESULTS: Thirty parents (29 mothers, 1 father) and their children with CP
      participated. Repeated-measures analysis of variance detected significant mean
      differences among the FIATS scores (F(1.4,40.6)=19.25, P<.001). Post hoc testing
      confirmed significant mean differences in overall FIATS scores between baseline
      and intervention and intervention and postintervention phases. The test of within
      subject effects did not detect a significant change among IFS mean scores.
      CONCLUSIONS: The introduction of adaptive seating devices for young children who
      need support to sit had a meaningful, positive impact on child and family life.
      Removal of the study devices showed a concomitant negative impact on key aspects
      of child and family life. Environmental resources, such as seating and other
      assistive technology devices, may have an important role to play in the lives of
      young children with physical disabilities and their families.

PMID- 19154827
TI  - Prevention of slip-related backward balance loss: the effect of session intensity
      and frequency on long-term retention.
AB  - OBJECTIVE: To examine the effects of session intensity (number of slip exposures)
      and frequency on the retention of acquired adaptation for prevention of backward
      balance loss after repeated-slip training. DESIGN: A 4-group, randomized, and
      controlled study. SETTING: Biomechanics research laboratory. PARTICIPANTS:
      Healthy young subjects (N=46; 21 men). INTERVENTIONS: Twenty-four subjects
      experienced a high-intensity session of 24 repeated right-side slips; 12 received
      additional single-slip sessions at a frequency of 1 week, 2 weeks, and 1 month,
      whereas the rest got no ancillary training. Another 24 subjects received a low
      intensity initial session of a single slip; 12 received the same high-frequency
      ancillary training, whereas the rest got none. All groups were retested with a
      single slip 4 months after the first session. MAIN OUTCOME MEASURES: The
      incidence of backward balance loss, gait stability, and limb support. RESULTS:
      The high-intensity groups, irrespective of ancillary training, displayed similar
      improvements in all 3 outcome measures. Remarkably, the low-intensity group
      receiving ancillary training also significantly improved in all measures, with
      retention comparable to that observed in the other 2 groups. A single-slip
      exposure without ancillary sessions was insufficient to yield a longer-term
      effect. CONCLUSIONS: Frequent ancillary sessions may be unnecessary for slip
      related fall prevention up to 4 months if the initial session intensity is
      sufficient. Furthermore, the minimum of a single slip may be as effective if the
      subject is exposed to frequent ancillary sessions.

PMID- 19154828
TI  - Changes in walking activity and endurance following rehabilitation for people
      with Parkinson disease.
AB  - OBJECTIVE: To investigate changes in walking activity and endurance after
      interdisciplinary rehabilitation in people with Parkinson disease (PD). DESIGN:
      Randomized controlled trial. SETTING: Clinic, home, and community. PARTICIPANTS:
      Mild to moderate PD (Hoehn and Yahr stage 2-3). INTERVENTIONS: Three experimental
      conditions lasting 6 weeks in duration: (1) no active rehabilitation; (2) 3.0
      hours of interdisciplinary rehabilitation a week; or (3) 4.5 hours of
      interdisciplinary rehabilitation a week. Participants had stable medication
      regimes during the study. MAIN OUTCOME MEASURES: Walking activity was estimated
      with an activity monitor (AM) (time spent walking and number of 10-second walking
      periods) in the home and community settings over a 24-hour period. Walking
      endurance was measured in the clinic with the two-minute walk test (2MWT). Linear
      contrast analyses were applied to examine changes in walking activity and
      endurance after higher doses of rehabilitation, and 2-way analysis of variance
      models with interaction were applied to examine the effect of high and low
      baseline walking levels on changes. RESULTS: The 2MWT was completed by 108 people
      with PD (mean age, 66.53y; with PD, 6.59y), and AM data were used from 74 of
      these people (mean age, 66.7y; with PD, 5.8y). Improvement in AM measures and the
      2MWT did not significantly change across increasing dosages of interdisciplinary
      rehabilitation. Higher doses of rehabilitation resulted in significant
      improvements in the 2MWT for subjects with low baseline walking endurance
      (P=.001), and in AM measures for subjects with high baseline walking activity
      (P<.02). CONCLUSIONS: Interdisciplinary rehabilitation can improve walking
      activity and endurance depending on baseline walking levels.

PMID- 19154829
TI  - Can the six-minute walk test predict peak oxygen uptake in men with heart
      transplant?
AB  - OBJECTIVE: To determine whether the six-minute walk test (6MWT) might predict
      peak oxygen consumption (VO2peak) after heart transplantation. DESIGN: Case
      control prospective study. SETTING: Public hospital. PARTICIPANTS: Patients with
      heart transplant (n=22) and age-matched sedentary male subjects (n=13).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Exercise performance using
      a maximal exercise test, distance walked using the 6MWT, heart rate, and VO2peak.
      RESULTS: Compared with controls, exercise performance was decreased in patients
      with heart transplant with less distance ambulated (516+/-13m vs 592+/-13m;
      P<.001) and a decrease in mean VO2peak (23.3+/-1.3 vs 29.6+/-1mL x min(-1) x kg(
      1); P<.001). Patients with heart transplant showed an increased resting heart
      rate, a response delayed both at the onset of exercise and during recovery.
      However, the patient's heart rate at the end of the 6MWT was similar to that
      obtained at the ventilatory threshold. The formula did not predict measured VO2,
      with a weak correlation observed between the six-minute walk distance and both
      VO2peak (r=.53; P<.01) and ventilatory threshold (r=.53; P<.01) after heart
      transplantation. Interestingly, when body weight was considered, correlations
      coefficient increased to .74 and .77, respectively (P<.001). CONCLUSIONS: In
      heart transplant recipients, the 6MWT is a safe, practical, and submaximal
      functional test. The distance-weight product can be used as an alternative method
      for assessing the functional capacity after heart transplantation but cannot
      totally replace maximal VO2 determination.

PMID- 19154830
TI  - Reliability of ambulatory walking activity in patients with hematologic
      malignancies.
AB  - OBJECTIVES: To determine the relative and absolute reliability of the assessment
      of ambulatory walking activity during 2 consecutive weeks in patients with
      hematologic malignancies recovering at home from their medical treatment and to
      compare the physical activity level of hematologic cancer patients after high
      dose chemotherapy with healthy subjects. DESIGN: Test-retest study of 2
      consecutive 7-day recordings using the microprocessor-based step accelerometer 3
      (SAM3). SETTING: Home and community. PARTICIPANTS: Patients (n=23) with
      hematologic malignancies recovering from high-dose chemotherapy and healthy
      controls (n=30). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The
      intraclass correlation coefficient (ICC(3,1)) and its 95% confidence interval
      (CI), SE of measurement procedure and its 95% CI, the smallest detectable
      difference (SDD), the coefficient of variation (CV), and t tests for the
      variables total steps and peak activity. RESULTS: The day-to-day and week-to-week
      CVs for walking activity and peak activity were 35.17% and 13.17% and 18.61% and
      6.90%, respectively. For relative reliability, the ICCs for 2 consecutive 7-day
      recordings including the 95% CI for total steps and peak activity were 0.90 (95%
      CI, 0.75-0.98) and 0.85 (95% CI, 0.66-0.94), respectively. The absolute
      reliability for total steps and peak activity including the SE of measurement
      procedure and the 95% CI were 564 (95% CI, +/-1106) and 2.42 steps (95% CI, +/
      4.74), respectively, for 2 consecutive 7-day recordings. The week-to-week SDD was
      1564 for total steps and 6.70 for peak activity. The 7-day mean for total step
      activity was 5355 for the patients with hematologic malignancies and 6364 for
      healthy subjects (P<0.05). CONCLUSIONS: The results of this study indicate that
      there is good relative reliability for the assessment of 2 consecutive 7-day
      recordings of ambulatory walking activity, and it showed that the SDD derived
      from this sample may be useful in detecting changes in daily walking activity in
      hematologic cancer patients who are recovering from intensive medical treatment.
      The study also documented compromised levels of ambulatory walking activity among
      hematologic cancer patients recovering from high-dose chemotherapy as compared
      with healthy controls.

PMID- 19154832
TI  - Determinants of skin problems of the stump in lower-limb amputees.
AB  - OBJECTIVE: To identify determinants of skin problems in lower-limb amputees.
      DESIGN: Survey, using a questionnaire. SETTING: Not applicable. PARTICIPANTS:
      Lower-limb amputees (N=2039) who either obtained their prosthesis through the
      Orthopedische Instrument Makerij (a group of orthopedic workshops in the
      Netherlands) or were a member of the (Dutch) National Society of Amputees
      (Landelijke Vereniging van Geamputeerden) were invited to participate. In total,
      872 lower-limb amputees agreed to participate. INTERVENTION: Amputees filled in
      the questionnaire to assess characteristics of the amputation and prosthesis,
      level of activity, stump and prosthesis hygiene, and skin problems. Stepwise
      backward logistic regression was performed to analyze determinants of skin
      problems. MAIN OUTCOME MEASURE: Skin problems in the month prior to completing
      the questionnaire. RESULTS: A total of 816 questionnaires were received.
      Eventually 805 questionnaires were suitable for statistical analysis. Protective
      determinants were (in order of magnitude of association) older age, male sex, and
      amputation because of peripheral arterial disease and/or diabetes. Provocative
      determinants were (in order of magnitude of association) use of antibacterial
      soap, smoking, and washing the stump 4 times a week or more often. In total, 63%
      of the participants (95% confidence interval, 60%-67%) reported 1 or more skin
      problems. CONCLUSIONS: The provocative determinants identified in this study--use
      of antibacterial soap, smoking, and stump washing frequency--have to be studied
      for their clinical relevance.

PMID- 19154833
TI  - Diagnostic value of history taking and physical examination to assess effusion of
      the knee in traumatic knee patients in general practice.
AB  - OBJECTIVE: To assess the diagnostic value of history taking and physical
      examination for knee joint effusion in patients with a knee injury who consult
      their general practitioner (GP). In addition, to determine the association
      between effusion seen on magnetic resonance imaging (MRI) and internal
      derangement of the knee. DESIGN: Prospective, observational cohort study.
      SETTING: Primary care. PARTICIPANTS: Patients (N=134) aged 18 to 65 years with a
      traumatic knee injury who consulted their GP. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Patients filled out a questionnaire, underwent a standardized
      physical examination and underwent an MRI scan to assess the presence of
      effusion. Multivariate logistic regression analysis was used to determine the
      diagnostic value of history taking and physical examination (P<0.10) as assessed
      by sensitivity, specificity, predictive values, and likelihood ratios. The
      relationship between effusion and internal derangement of the knee was assessed
      with a chi-square test. RESULTS: Of the 134 participating patients, 42 had knee
      joint effusion seen on MRI. Multivariate analysis showed an association with knee
      joint effusion for the symptom "self-noticed swelling" (history taking) and for
      the "ballottement test" (physical examination). The likelihood ratio positive
      (LR+) was 1.5 for self-noticed swelling and 1.6 for the ballottement test. These
      2 combined improved the diagnostic value to an LR+ of 3.6. Effusion showed a
      positive association with internal derangement of the knee (chi-square 9.5); 31
      of the 42 patients with knee joint effusion had internal derangement of the knee.
      CONCLUSIONS: In patients with traumatic knee injury, knee joint effusion is
      frequently seen on MRI. The combination of self-noticed swelling and the
      ballottement test was of diagnostic value. Knee joint effusion was associated
      with internal derangement of the knee.

PMID- 19154831
TI  - Functional overloading of dystrophic mice enhances muscle-derived stem cell
      contribution to muscle contractile capacity.
AB  - OBJECTIVES: To evaluate the effect of functional overloading on the
      transplantation of muscle derived stem cells (MDSCs) into dystrophic muscle and
      the ability of transplanted cells to increase dystrophic muscle's ability to
      resist overloading-induced weakness. DESIGN: Cross-sectional. SETTING:
      Laboratory. ANIMALS: Male mice (N=10) with a dystrophin gene mutation.
      INTERVENTIONS: MDSCs were intramuscularly transplanted into the extensor
      digitorum longus muscle (EDL). Functional overloading of the EDL was performed by
      surgical ablation of the EDL's synergist. MAIN OUTCOME MEASURES: The total number
      of dystrophin-positive fibers/cross-section (as a measure of stem cell
      engraftment), the average number of CD31+ cells (as a measure of capillarity),
      and in vitro EDL contractile strength. Independent t tests were used to
      investigate the effect of overloading on engraftment, capillarity, and strength.
      Paired t tests were used to investigate the effect of MDSC engraftment on
      strength and capillarity. RESULTS: MDSC transplantation protects dystrophic
      muscles against overloading-induced weakness (specific twitch force: control
      4.5N/cm2+/-2.3; MDSC treated 7.9N/cm2+/-1.4) (P=.02). This improved force
      production following overloading is concomitant with an increased regeneration by
      transplanted MDSCs (MDSC: 26.6+/-20.2 dystrophin-positive fibers/cross-section;
      overloading + MDSC: 170.6+/-130.9 dystrophin-positive fibers/cross-section
      [P=.03]). Overloading-induced increases in skeletal muscle capillarity is
      significantly correlated with increased MDSC engraftment (R2=.80, P=.01).
      CONCLUSIONS: These findings suggest that the functional contribution of
      transplanted MDSCs may rely on activity-dependent mechanisms, possibly mediated
      by skeletal muscle vascularity. Rehabilitation modalities may play an important
      role in the development of stem cell transplantation strategies for the treatment
      of muscular dystrophy.

PMID- 19154834
TI  - Reliability of rehabilitative ultrasound imaging of the transversus abdominis and
      lumbar multifidus muscles.
AB  - OBJECTIVES: To evaluate the intraexaminer and interexaminer reliability of
      rehabilitative ultrasound imaging (RUSI) in obtaining thickness measurements of
      the transversus abdominis (TrA) and lumbar multifidus muscles at rest and during
      contractions. DESIGN: Single-group repeated-measures reliability study. SETTING:
      University and orthopedic physical therapy clinic. PARTICIPANTS: A volunteer
      sample of adults (N=30) with current nonspecific low back pain (LBP) was examined
      by 2 clinicians with minimal RUSI experience. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Thickness measurements of the TrA and lumbar multifidus muscles
      at rest and during contractions were obtained by using RUSI during 2 sessions 1
      to 3 days apart. Percent thickness change was calculated as thickness(contracted)
      thickness(rest)/thickness(rest). Intraclass correlation coefficients (ICC) were
      used to estimate reliability. RESULTS: By using the mean of 2 measures,
      intraexaminer reliability point estimates (ICC(3,2)) ranged from 0.96 to 0.99 for
      same-day comparisons and from 0.87 to 0.98 for between-day comparisons.
      Interexaminer reliability estimates (ICC(2,2)) ranged from 0.88 to 0.94 for
      within-day comparisons and from 0.80 to 0.92 for between-day comparisons.
      Reliability estimates comparing measurements by the 2 examiners of the same image
      (ICC(2,2)) ranged from 0.96 to 0.98. Reliability estimates were lower for percent
      thickness change measures than the corresponding single thickness measures for
      all conditions. CONCLUSIONS: RUSI thickness measurements of the TrA and lumbar
      multifidus muscles in patients with LBP, when based on the mean of 2 measures,
      are highly reliable when taken by a single examiner and adequately reliable when
      taken by different examiners.

PMID- 19154835
TI  - Behavioral risk factors of mortality after spinal cord injury.
AB  - OBJECTIVE: To test hypothesized relationships between multiple behavioral
      indicators and mortality among persons with spinal cord injury (SCI), while
      controlling for biographic and injury characteristics. DESIGN: Prospective cohort
      study with behavioral data collected by mailed survey in late 1997 and early
      1998. Mortality status was ascertained as of December 31, 2005. SETTING: A large
      rehabilitation hospital in the southeastern United States. PARTICIPANTS: Adults
      (N=1386) with traumatic SCI, at least 1 year postinjury. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Primary outcome was time from survey to
      mortality or censoring. Mortality status was determined using the National Death
      Index and the Social Security Death Index. There were 224 deaths (16.2%) in the
      full sample, and due to missing data, 188 deaths were observed in the 1251
      participants included in the final statistical model. RESULTS: Cox proportional
      hazards modeling identified several significant behavioral predictors of
      mortality. In the first set of analyses, the significance of a single behavioral
      variable was assessed while controlling for biographic and injury predictors. We
      subsequently built a comprehensive model based on an optimal group of behaviors.
      The best set of behavioral predictors included: smoking, binge drinking (number
      of episodes with 5 or more drinks), prescription medication use, and number of
      hours out of bed per day. Inclusion of these variables improved prediction of
      survival compared with biographic and injury variables alone, as the pseudo-R2
      increased from .121 to .164 and the concordance from .730 to .769. CONCLUSIONS:
      The results affirm the importance of avoiding basic risk behaviors, such as
      smoking and alcohol misuse, and affirm their importance as targets of
      intervention in association with SCI rehabilitation.

PMID- 19154836
TI  - Use of a combination of ankle pressure and SENSERite system to treat older adults
      with impaired ankle proprioception: a single-blind experimental study.
AB  - OBJECTIVE: To investigate the effects of a combination of visual biofeedback and
      ankle pressure on ankle position sense in elderly adults with and without
      impaired ankle joint position sense (JPS). DESIGN: Independent 2 x 3 factorial
      design with an experimenter-blind study. SETTING: University motion laboratory.
      PARTICIPANTS: Older adults (N=40) were recruited from local community centers.
      Among them, 21 elderly subjects had relatively normative score, whereas 19
      subjects had impaired ankle position sense. INTERVENTION: Both the normative and
      impaired elderly subjects underwent either ankle JPS visual feedback training
      alone or a combination of ankle JPS visual feedback training and circumferential
      ankle pressure for one 30-minute training session. MAIN OUTCOME MEASURES: The
      outcome measures included ankle JPS errors measured in absolute constant error
      (ACE) and variable error (VE) during standing at pretest, posttest, and 1-week
      follow-up test. A separate repeated measures analyses of variance was performed
      to evaluate the differential training effects on ACE and VE, respectively. The
      Pearson chi-square test and Bonferroni test were performed. Significance was
      assigned at P less than .05 for all analyses. RESULTS: Regardless of intervention
      conditions, older adults with and without ankle position sense impairment showed
      immediate treatment benefits, which relatively remained stable even at the follow
      up test. These effects were reflected in significant improvements of JPS accuracy
      and consistency (P<.05). CONCLUSIONS: Our findings may suggest that both
      interventions were equally effective in increasing ankle JPS accuracy and
      consistency in older adults with and without impairments, and therapeutic effects
      lasted for a week, reflecting long-term effect.

PMID- 19154837
TI  - Is the fear avoidance model associated with the reduced level of aerobic fitness
      in patients with chronic low back pain?
AB  - OBJECTIVES: To compare aerobic fitness of patients with chronic low back pain
      (CLBP) against healthy controls and to assess whether variables of the fear
      avoidance model are associated with loss of aerobic fitness. DESIGN: A case
      comparison study. SETTING: Rehabilitation centers. PARTICIPANTS: Patients with
      CLBP (n=223), and normative data from healthy subjects (n=18,082). INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Maximal oxygen uptake (VO2max) was
      estimated on the basis of a modified submaximal Astrand bicycle test performed by
      patients with CLBP (observed level of aerobic fitness) and compared with the
      normative data of healthy controls matched for age, sex, and level of sport
      activity (expected level of aerobic fitness). Pain (visual analog scale);
      disability (Roland Disability Questionnaire); pain-related fear (Tampa Scale for
      Kinesiophobia); depression (Beck Depression Inventory); catastrophizing (Pain
      Catastrophizing Scale); and the level of activity during sport, work/household,
      and leisure time (Baecke Physical Activity Questionnaire) were assessed. Multiple
      linear regression analysis was performed with the difference of the observed and
      expected level of aerobic fitness as dependent variable and putative influential
      factors including those of the fear avoidance model as independent variables.
      RESULTS: VO2max could be calculated in 175 (78%) of the patients. Both men and
      women with CLBP had significant lower VO2max than expected (10.3mL/kg lean body
      mass (LBM)xmin(-1) and 6.5mL/kg LBMxmin(-1), respectively; P<.001). The levels of
      activity during leisure time and work/household were significantly associated
      with this reduced level of aerobic fitness. However, the variables of the fear
      avoidance model were not. CONCLUSIONS: Most patients with CLBP-associated
      disability have a lower level of aerobic fitness, but this is not associated with
      fear avoidance.

PMID- 19154838
TI  - Exercises for spine stabilization: motion/motor patterns, stability progressions,
      and clinical technique.
AB  - OBJECTIVE: To quantify several forms of the curl-up, side-bridge, and birddog
      exercises (muscle activity and 3-dimensional [3D] spine position) including some
      corrective techniques to assist clinical decision-making. DESIGN: A basic science
      study of a convenience sample with a retest of expert intervention. SETTING:
      Spine Biomechanics Laboratory/Research Clinic. PARTICIPANTS: Healthy men (N=8)
      performed the exercises, and 5 subjects repeated the exercises as an expert
      applied corrective techniques. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Surface electromyography of selected trunk and hip muscles together
      with video analysis and 3D spine posture were collected. RESULTS: Comparison of
      muscle activation levels showed there were justifiable progressions in each
      exercise form. In general, bracing of the abdominal wall enhanced activation of
      the obliques, but different techniques caused migration of muscle activity to
      other muscles. Examples of specific findings include the following. Movement
      during these traditionally isometric exercises such as drawing squares with the
      hand/foot while in the birddog posture enhances activation of many muscle groups.
      Breathing while holding the isometric exercises had differing effects on muscle
      activation which was exercise dependent. Some corrective exercise techniques,
      such as fascial raking, substantially changed relative activation between muscles
      in the abdominal wall. CONCLUSIONS: The data presented in this study may be used
      to guide the clinical decision process when choosing a specific exercise form
      together with selecting the correct starting level, a logical progression,
      suitable dosage, and possible corrective technique to enhance tolerance of a
      patient.

PMID- 19154839
TI  - Energy transfer across the lumbosacral and lower-extremity joints in patients
      with low back pain during sit-to-stand.
AB  - OBJECTIVE: To examine the transfer of energy through the pelvis and the lower
      limb during sit-to-stand (STS) in low back pain (LBP) subjects with or without a
      straight-leg raise sign. DESIGN: Cross-sectional. SETTING: Biomechanics
      laboratory. PARTICIPANTS: Three groups, each of 20 subjects, participated. The
      first group consisted of asymptomatic subjects, and the other 2 groups of
      consisted of LBP subjects (duration between 7 days and 12 weeks) with and without
      a straight-leg raise sign. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      The work done and the power of the pelvis, thigh, and leg segments during STS
      were determined. RESULTS: Energy was transferred from the pelvis to the thigh
      segment and then to the leg segment, and this was achieved mainly by passive
      mechanisms. The power flow of the pelvis segment was significantly decreased in
      subjects with LBP. Although the power of the lower-limb segments was decreased,
      the total work done of these segments was increased. CONCLUSIONS: STS is a more
      energy-demanding and less efficient task for subjects with LBP, either with or
      without a positive straight-leg raise sign. Such increases in energy demand may
      further exacerbate back pain, and treatment should be developed to restore a more
      efficient energy transfer pattern.

PMID- 19154840
TI  - Metabolic and mechanical energy costs of reducing vertical center of mass
      movement during gait.
AB  - OBJECTIVES: To test the hypothesis that reducing vertical center of mass (COM)
      displacement will lower the metabolic cost of human walking. To examine changes
      in joint work associated with increasing and decreasing vertical COM movement
      during gait. DESIGN: Randomized repeated measures. SETTING: Human Neuromechanics
      Laboratory, University of Michigan. PARTICIPANTS: Able-bodied subjects (N=10).
      INTERVENTIONS: Subjects walked at 1.2m/s on a treadmill and overground. Subjects
      manipulated vertical COM displacement either by adjusting stride length or by
      using visual feedback to reduce COM movement. MAIN OUTCOME MEASURES: We measured
      kinematic and kinetic data to calculate vertical and lateral COM displacements,
      joint torques, and work. In addition, we collected oxygen consumption to
      calculated metabolic power. RESULTS: Increasing and decreasing vertical COM
      displacement beyond subjects' preferred range resulted in increases in the
      metabolic cost of walking. When vertical COM displacement was reduced,
      corresponding increases in positive ankle and hip work and negative knee work
      were observed. CONCLUSIONS: Humans are capable of walking in a manner that will
      reduce COM displacement from normal. Decreasing vertical COM movement results in
      increases in metabolic energy costs because of greater mechanical work performed
      at the hip, knee, and ankle joints. Thus, reducing vertical COM movement is not a
      successful strategy for improving either metabolic or mechanical energy economy
      during normal walking by able-bodied subjects.

PMID- 19154841
TI  - A comparison of balance performance: computerized dynamic posturography and a
      random motion platform.
AB  - OBJECTIVE: To establish the clinical utility of the PROPRIO 5000 as a balance
      assessment device by establishing convergent validity with the NeuroCom sensory
      organization test (SOT). DESIGN: Cross-sectional. SETTING: Balance research
      laboratory. PARTICIPANTS: Young adults (N=40; 21.1+/-1.4y). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Performance on each of the 6 NeuroCom SOT
      testing conditions and PROPRIO 5000 dynamic motion analysis score. RESULTS:
      Correlational analyses between output variables yielded significant relationships
      between the dynamic motion analysis score from the 0 to 10 second (r=-.38), 10 to
      20 second (r=-.34), and 20 to 30 second (r=-.35) intervals and the SOT composite
      balance score. CONCLUSIONS: The initial stages of the PROPRIO 5000 and the
      NeuroCom SOT battery may evaluate similar aspects of postural control. However,
      as the magnitude of PROPRIO perturbations increased, the relationship between the
      devices diverged and the complete PROPRIO assessment is not thought to pair with
      the SOT assessment. Differences between the 2 devices may be associated with
      varying degrees of test difficulty and the necessary postural control strategies
      involved in responding to continual balance perturbations (PROPRIO 5000) or to
      different sensory inputs (SOT).

PMID- 19154842
TI  - Clinimetric properties of instruments to assess activities in patients with hand
      injury: a systematic review of the literature.
AB  - OBJECTIVE: To perform a systematic review of the literature to assess the
      clinimetric properties of instruments measuring limitations of activity. DATA
      SOURCES: The Medline, Cochrane Library, Picarta, Occupational Therapy-seeker, and
      CINAHL databases were searched for English or Dutch language articles published
      between 2001 and 2006. STUDY SELECTION: Two reviewers independently reviewed the
      identified publications for eligibility (based on the title and abstract),
      methodologic criteria, and clinimetric properties. To evaluate the available
      information of the clinimetric properties, the quality criteria for instrument
      properties were used. DATA EXTRACTION: All the clinimetric properties of the 23
      instruments were described based on the publications that were included. DATA
      SYNTHESIS: In total, 103 publications were retrieved, 79 of which were eligible
      for inclusion. Of these, 54 met the methodologic quality criteria. Twenty-three
      instruments were reviewed, divided into (1) pegboard tests measuring fine hand
      use only; (2) instruments measuring fine hand use only, by picking up,
      manipulating, and placing different objects; (3) instruments measuring single
      tasks (and fine hand use) by scoring task performance; and (4) questionnaires.
      The reliability, validity, and responsiveness of only 5 instruments were
      adequately described in the literature; the description of the clinimetric
      properties of the other instruments was inadequate. CONCLUSIONS: None of the
      instruments had a positive rating for all the clinimetric properties.

PMID- 19154843
TI  - Functional outcome in a patient with an acute quadriparesis secondary to systemic
      sclerosis: a case report.
AB  - Scleroderma or systemic sclerosis (SSc) is a relatively uncommon disease.
      Although well-known for many years, research on appropriate physical therapy
      during all stages of myositis due to scleroderma is limited. We report the
      functional outcome in a patient with an acute quadriparesis secondary to diffuse
      SSc associated with extensive myositis. This 35-year-old black woman progressed
      to almost complete functional recovery in the course of 16 days of acute
      rehabilitation with combined physical therapy including resistive exercises. This
      case strongly suggests that a patient with diffuse SSc and associated myositis
      can undergo aggressive physical therapy in a monitored environment with good
      functional improvement and no worsening of the myositis.

PMID- 19154844
TI  - Safety, acceptance, and physiologic effects of sauna bathing in people with
      chronic heart failure: a pilot report.
AB  - OBJECTIVES: To perform a pilot study and make a preliminary assessment of the
      safety and acceptance of supervised sauna bathing at moderate temperatures in
      people with chronic heart failure (CHF). Secondary measures included its impact
      on exercise tolerance and neuroendocrine concentrations. DESIGN: Randomized,
      controlled, cross-over trial. SETTING: Physical medicine and rehabilitation
      clinic. PARTICIPANTS: Six men and 3 women (age, 62-87y) with New York Heart
      Association Class III and IV CHF. INTERVENTIONS: Subjects were randomized into 2
      groups and told to maintain their normal medication and activity regimens. One
      group then began a 3-times-a-week, 4-week sauna bathing program at 60+/-1 degrees
      C while the other continued with their usual activities and medications.
      Assignments were then reversed. Sessions were 15 minutes in length but were
      prolonged an additional 5 minutes for oral temperature increases less than 1.0
      degrees C. MAIN OUTCOME MEASURES: Patient acceptance, Minnesota Living With Heart
      Failure Questionnaire (MLWHFQ) scores; treadmill exercise duration and plasma
      adrenaline, noradrenalin, aldosterone, atrial naturectic factor, adrenomedulin,
      and endothelin. RESULTS: Sauna bathing was well tolerated and no adverse effects
      were reported. Improvements in MLWHFQ scores and treadmill endurance did not
      achieve statistical significance on a between-group basis but were more marked
      after the sauna than during the control phase. Neuroendocrine concentrations
      showed no clear effect of sauna treatment with a between-group statistically
      significant difference (P=.049) found only in the case of noradrenalin's 24%
      decrease. CONCLUSIONS: Sauna bathing under the moderate and supervised conditions
      of this study appears to be well tolerated and may be safe for people with CHF.
      More research is needed to further evaluate the safety and potential benefits of
      this approach.

PMID- 19154845
TI  - Restoration of voluntary muscle strength after 3 weeks of cast immobilization is
      suppressed in women compared with men.
AB  - OBJECTIVE: To investigate sex-related differences in the loss and recovery of
      voluntary muscle strength after immobilization. DESIGN: Longitudinal, repeated
      measures. SETTING: Research laboratory. PARTICIPANTS: Healthy men (n=5) and
      healthy women (n=5). INTERVENTION: Three weeks of forearm immobilization. MAIN
      OUTCOME MEASURES: Voluntary wrist flexion muscle strength was assessed at
      baseline and weekly during the immobilization protocol and 1 week after cast
      removal. Central activation was assessed before and after immobilization and
      after 1 week of recovery to determine what percentage of the muscle could be
      activated voluntarily. RESULTS: Men and women lost voluntary strength at a
      similar rate during immobilization. However, after 1 week of recovery voluntary
      strength had returned to within 1% of baseline in the men, but remained
      approximately 30% less than baseline in the women (P=0.03). Both sexes displayed
      reduced central activation after immobilization (P=0.02), but the decrease was
      similar in both sexes (P=0.82). CONCLUSIONS: These findings suggest sex-dependent
      adaptations to and recovery from limb immobilization, with voluntary strength
      recovering slower in women. As such, sex-specific rehabilitation protocols may be
      warranted, with women requiring additional or more intensive rehabilitation
      programs after periods of disuse. Future work is needed to determine the extent
      and mechanisms of these differences.

PMID- 19154846
TI  - Several trials are useful to reduce the value of minimal detectable change.

PMID- 19154847
TI  - An alternative explanation.

PMID- 19154849
TI  - Disease-a-month. Foreword.

PMID- 19154850
TI  - Menstrual disorders in adolescent females: current concepts.

PMID- 19154851
TI  - Psychosomatic medicine: a specialty for generalists.

PMID- 19154852
TI  - Symptom experience after solid organ transplantation.
AB  - OBJECTIVES: Understanding patients' perceptions and responses to
      immunosuppression-related symptom experiences following solid organ
      transplantation increases the likelihood that interventions can be designed to
      support long-term graft survival. METHODS: This review summarizes and integrates
      evidence on transplant patients' symptom experiences related to immunosuppression
      side-effects in terms of symptom occurrence and symptom distress and other
      aspects of posttransplant treatment regimen. Empirical data of 18 reports on
      symptom experiences published between 1981 and April 2008 have been analyzed
      systematically. This report is organized to address the following areas of
      findings: (1) overview about instruments to assess symptom experiences, (2)
      descriptive information concerning symptom occurrence and related distress, (3)
      potential impact of symptom experiences on patient adherence, and (4) review of
      evidence between symptom experiences and health outcomes in terms of health
      related quality of life (HRQoL). RESULTS: Symptom experience scores remain high
      among all types of solid organ transplantation including kidney, liver, heart,
      and lung transplant, with no patterns related to symptom occurrence and distress.
      "Female gender" is consistently related to higher levels of symptom occurrence
      and symptom distress. Understanding the patients' appraisal of symptoms and side
      effects related to the immunosuppressive therapy is a key to step forward by
      developing strategies to (1) reducing nonadherence triggered by symptom
      occurrence and distress, (2) decreasing non-adherence-related rejection, and (3)
      improving HRQoL by tailored symptom management. CONCLUSION: As many side-effects
      are related to particular immunosuppressive drugs and dosages, a more in-depth
      understanding of the relationships among the concepts of symptom experience,
      nonadherence, and HRQoL may guide clinical decision making in the future.

PMID- 19154853
TI  - Cognitions associated with anxiety in Meniere's disease.
AB  - OBJECTIVES: The purpose of this longitudinal study was to identify cognitions
      associated with anxiety and maintenance of anxiety in people with Meniere's
      disease. METHOD: At baseline, participants completed the Hospital Anxiety and
      Depression Scale (HADS), the Revised Illness Perception Questionnaire, the
      Dizziness Beliefs Scale, the Fear-Avoidance Beliefs Questionnaire, the
      Intolerance of Uncertainty Scale, and measures of demographic and illness
      characteristics. Participants were then randomized to a no-treatment group or to
      receive one of two self-help booklets, and completed the HADS again at 3-month
      follow-up. RESULTS: After symptom severity had been controlled for, baseline
      anxiety was found to be associated with intolerance of uncertainty, fear
      avoidance of physical activity, belief that dizziness would develop into a severe
      attack of vertigo, and several illness perception subscales (emotional
      representations, consequences, psychological causes, and perceived treatment
      effectiveness). Anxiety on follow-up was predicted by higher baseline levels of
      autonomic/somatic symptoms and intolerance of uncertainty, and by reporting less
      understanding of the illness. These longitudinal relationships were found in
      those who did and who did not receive self-help booklets. CONCLUSIONS: Our
      findings suggest that intolerance of uncertainty is associated with anxiety in
      Meniere's disease. A controlled trial is needed to see whether anxiety might be
      reduced in Meniere's disease by helping patients tolerate and cope with
      uncertainty.

PMID- 19154854
TI  - Development of chronic pain following severe accidental injury. Results of a 3
      year follow-up study.
AB  - OBJECTIVE: Motor vehicle accidents (MVA) and work-related injuries are two of the
      more common causes of chronic pain. Nevertheless, there is little evidence on
      predicting factors regarding the development of chronic pain following physical
      injury. METHODS: The present study investigated temporal associations between
      accident-related factors, psychological factors [symptoms of posttraumatic stress
      disorder (PTSD), anxiety, depression, coping], and the development of chronic
      pain in a sample of individuals who had sustained severe accidental injuries
      (N=90). Assessments were performed within 1 month of the accident, and at 6, 12,
      and 36 months post trauma. RESULTS: A total of 40 individuals (44%) reported
      accident-related pain 3 years after the accident. Individuals with chronic pain
      showed significantly more symptoms of PTSD, depression, and anxiety, more
      disability, and more days off work. Analysis of temporal associations between
      psychological variables and the development of chronic pain indicated that the
      separation of the pain from the nonpain group mostly occurred between 6 (T2) and
      12 months (T3). Differences were much less pronounced at T1. CONCLUSION: The
      prevalence of chronic pain in severely injured patients 3 years after the
      accident is considerably high. The development of chronic pain is more related to
      psychological factors, particularly PTSD symptoms, in the aftermath of the
      accident, as compared to sociodemographic and accident-related variables at the
      time of the accident. These findings may be helpful to elucidate the problems in
      predicting chronic pain conditions in injured subjects and to recognize the onset
      of a chronic pain condition more reliably.

PMID- 19154855
TI  - Role of depressive symptoms and comorbid chronic disease on health-related
      quality of life among community-dwelling older adults.
AB  - OBJECTIVE: This study examined the influence of depressive symptoms on health
      related quality of life (HRQOL) among community-dwelling older adults suffering
      from various categories of chronic comorbidity. METHODS: A population-based
      survey in adults aged 60 years or more was conducted within a random sample of
      1085 beneficiaries of the Mexican Institute of Social Security in Mexico City.
      Depressive symptoms were evaluated with the 15-item Geriatric Depression Scale,
      and chronic comorbidity was determined with self-reports concerning prior medical
      diagnoses and the HRQOL Short Form-36 health survey. We carried out a stratified
      analysis by comorbidity category, evaluating the impact of depressive symptoms on
      HRQOL through an analysis of variance and modeling the independent association of
      depression symptoms with HRQOL using multiple linear regression analyses adjusted
      for comorbidity and other covariables. RESULTS: HRQOL scores were low in the
      presence of depressive symptoms, while their impact increased when chronic
      diseases were also present. The group with the poorest HRQOL was older adults
      suffering from both depressive symptoms and two or more chronic diseases (P<.05).
      The stratified analysis by comorbidity and multivariate analysis, adjusted for
      covariables, indicated that depressive symptoms and comorbidity had cumulative
      negative effects on HRQOL. CONCLUSION: The HRQOL of older adults deteriorated
      when depressive symptoms were present and decreased even further with the
      simultaneous occurrence of chronic illnesses. Identifying depression symptoms
      either alone or along with chronic conditions-is crucial for implementation of
      measures aimed at improving elderly people's HRQOL.

PMID- 19154856
TI  - Changes in mental health as a predictor of changes in working time arrangements
      and occupational mobility: results from a prospective cohort study.
AB  - OBJECTIVE: The aim of this prospective study was to gain insight into a possible
      causal relationship between mental health and characteristics of the work
      situation. METHODS: Using longitudinal data from the Maastricht Cohort Study,
      this study examines whether deterioration in mental health (prolonged fatigue,
      need for recovery, and psychological distress) results in a subsequent change in
      working time arrangements (assessed by means of logistic regression analysis) or
      occupational mobility (assessed by means of Cox regression analysis). RESULTS:
      Compared to employees not experiencing a deterioration in mental health,
      employees who became a prolonged fatigue case were more likely to reduce their
      working hours (OR 2.49; 95% CI 1.42-4.35) and leave a shift work job (OR 3.44;
      95% CI 1.42-8.38). Employees who became a need for recovery case were more likely
      to reduce their working hours (OR 2.83; 95% CI 1.53-5.26) or change jobs within
      the company (RR 1.31; 95% CI 1.07-1.61). Employees who became a psychological
      distress case were more likely to change jobs within the company (RR 1.38; 95% CI
      1.16-1.65) or to change jobs from one employer to another (RR 1.45; 95% CI 1.03
      2.03). CONCLUSION: The results of this study provide evidence for a possible
      causal relationship between deterioration in mental health and subsequent change
      in working time arrangements or occupational mobility. These results suggest that
      workers adapt to the onset of a mental health problem by reducing their working
      hours, by leaving a shift work job, by changing jobs within the company, or by
      changing jobs from one employer to another.

PMID- 19154858
TI  - Personality and participation in mass health checkups among Japanese community
      dwelling elderly.
AB  - OBJECTIVE: The aim of this study is to examine the relationship between
      personality traits and participation in mass health checkups among Japanese
      community-dwelling elderly. METHODS: A data set of 327 men and 519 women aged 70
      years and over was used in the analysis. The NEO Five-Factor Inventory was
      administered to assess the "big five" personality traits: neuroticism,
      extraversion, openness, agreeableness, and conscientiousness. RESULTS: In
      multivariate logistic regression analysis adjusted for gender, age, number of
      years of education, living alone, presence of psychiatric diseases, presence of
      chronic diseases, and history of hospitalization during a 1-year period, openness
      was independently associated with participation in mass health checkups [odds
      ratio (OR)=1.51, 95% confidence interval (CI)=1.08-2.12, P<.01 and OR=1.38, 95%
      CI=0.96-1.97, P=.07 for the middle and highest tertile, respectively]. No other
      domains of personality were related to participation in the checkups.
      CONCLUSIONS: The results of the present study suggest that older individuals high
      in openness are likely to take part in checkups for the elderly. Our findings
      could help improve the participation rate in mass health checkups for the
      prevention of long-term care dependence in later life.

PMID- 19154857
TI  - Personality traits in women with multiple sclerosis: discrepancy in
      patient/partner report and disease course.
AB  - OBJECTIVE: Patients diagnosed with multiple sclerosis (MS) are believed to
      undergo personality changes, which could have implications for how they perceive
      themselves and are perceived by others. We endeavored to examine the extent to
      which patients' self-perceptions are congruent with how they are perceived by
      significant others across five trait domains as demarcated by the well known Five
      Factor Model (FFM). METHODS: The NEO Five-Factor Inventory (NEOFFI) (Costa and
      McCrae, 1992) was administered to women with MS (n=70) and their spouses or
      partners. Pearson correlations and general linear models (GLMs) were employed to
      test for differences between patient self-reports and partner reports of FFM
      traits. RESULTS: Correlation analyses revealed good correspondence between
      patient and partner NEOFFI data in relapsing-remitting MS patients, but not
      secondary progressive patients. There was no significant correlation among
      progressive course patients for all NEOFFI domains, except Agreeableness. GLMs
      revealed significant differences where patients rated themselves higher than
      their partners rated them in Extraversion and Openness. CONCLUSION: These
      discrepancies in the way patients and partners view patient personality are
      probably multidimensional and may have neurological and/or psychological causes.
      The direction of the discrepancies are consistent with some prior research
      suggesting MS, which is a disease affecting both the cerebral white and gray
      matter, may give rise to lowering in self awareness. Conversely, patients may be
      finding emotional or personal benefits in their response to the disease
      unbeknownst to partners.

PMID- 19154860
TI  - Viewing a humorous film decreases IgE production by seminal B cells from patients
      with atopic eczema.
AB  - OBJECTIVE: Sperms induced IgE production by seminal B cells from patients with
      atopic eczema via interaction of B cells with galectin-3 on sperms. We studied
      the effect of viewing a humorous film on IgE production by seminal B cells
      cultured with sperms. METHODS: Twenty-four male patients with atopic eczema
      viewed a humorous film (Modern Times, featuring Charlie Chaplin). Just before and
      immediately after viewing, semen was collected, and seminal B cells and sperms
      were purified. Seminal B cells were cultured with sperms and IgE production was
      measured, while expression of galectin-3 on sperms was assessed. RESULTS: After
      viewing the humorous film, IgE production by B cells cultured with sperms was
      significantly decreased. Moreover, expression of galectin-3 on sperms was
      reduced. CONCLUSION: Viewing a humorous film reduced galectin-3 expression on
      sperms, which in turn decreased IgE production by seminal B cells cultured with
      sperms. These results indicate that viewing a humorous film may be helpful for
      the study and treatment of local IgE production and allergy in the reproductive
      tract.

PMID- 19154859
TI  - Effects of faith/assurance on cortisol levels are enhanced by a spiritual mantram
      intervention in adults with HIV: a randomized trial.
AB  - OBJECTIVES: Previous research among HIV-infected individuals suggests that
      spiritual well-being is inversely related to psychological distress and rates of
      disease progression. Use of a mantram, a spiritual word or phrase repeated
      frequently and silently throughout the day, has been associated with decreased
      psychological distress and increased spiritual well-being. This study compared
      the effects of 2 interventions-a spiritually-based mantram intervention versus an
      attention-matched control group-on faith/assurance and average salivary cortisol
      levels among HIV-infected individuals. METHODS: Using a randomized design, HIV
      infected adults were assigned to the intervention (n = 36) or control condition
      (n = 35). Faith scores and saliva (collected at 7 a.m., 11 a.m., 4 p.m., and 9
      p.m.) were assessed at preintervention, postintervention, and 5-week follow-up.
      Path analyses tested competing models that specify both concurrent and sequential
      relationships between faith and average daily cortisol levels while comparing
      groups. RESULTS: Faith levels increased among mantram participants from pre- to
      postintervention. Greater faith at preintervention was significantly associated
      with lower average cortisol at postintervention in the mantram group but not in
      the controls. The associations between faith at postintervention and cortisol
      levels at 5-week follow-up were significant among both groups but weaker than the
      pre- to postintervention association identified in the mantram group.
      CONCLUSIONS: These results suggest the presence of lagged or antecedent
      consequent relationships between faith and cortisol, which may be enhanced by
      mantram use. Decreased cortisol could potentially benefit immune functioning
      among HIV-infected individuals.

PMID- 19154861
TI  - Behavioral observations reflected on consultation requests from primary medical
      surgical services: are they predictive of delirium diagnosis and outcomes?
AB  - OBJECTIVE: We studied 405 patients evaluated by the Psychosomatics Service to
      investigate whether the behavioral description as reflected on consultation
      request from primary medical-surgical teams could be utilized to predict the
      final clinical diagnosis of delirium. We explored whether outcomes differed in
      patient with delirium with different consultation requests. METHODS: Patients
      with delirium (n=114) were divided into subtypes based on consultation requests
      for the management for cognitive dysfunction [altered mental status (AMS), n=46],
      for agitation or behavior disturbance (BEH, n=26), for depression (DEP, n=18),
      and for all other reasons (MISC, n=33). Adjusted multivariate regression models
      were used to examine group differences. RESULTS: Consult requests for AMS had a
      high likelihood ratio (LR+=14.22) and requests for BEH had moderately high
      likelihood ratio (LR+=4.79) of receiving a diagnosis of delirium. The DEP group
      (n=18) tended to be younger and had higher 30-day readmission rates. The BEH
      group (n=26) had more comorbid systemic medical conditions, higher rate of being
      discharged to home, and lower mortality rate. Delirium subtypes did not show any
      significant difference in clinical outcomes. CONCLUSION: Behavioral observations
      on consultation requests as formulated by primary medical-surgical teams may be
      useful in the classification of patients with delirium. Whether the behavioral
      observations on the request may be used to predict delirium outcomes deserves
      further research.

PMID- 19154862
TI  - Psychosomatic medicine and consultation-liaison psychiatry in Hungary.

PMID- 19154863
TI  - Spontaneous rupture of the dissected coronary sinus mimicking acute coronary
      syndrome.

PMID- 19154864
TI  - Penetrating ulcer of the aortic arch presenting with hemoptysis.

PMID- 19154865
TI  - Concomitant cardiac and cerebral leiomyosarcoma: a challenge for surgical and
      adjuvant therapy.

PMID- 19154866
TI  - Cardiac echinococcosis of the interventricular septum in early childhood: report
      of two cases.

PMID- 19154867
TI  - Successful immediate cryorecanalization of a simultaneous high-grade tracheal and
      bronchial stenosis as rare manifestations of bronchial-associated lymphoid tissue
      lymphoma.

PMID- 19154868
TI  - New-onset heart failure caused by spontaneous papillary muscle rupture: diagnosis
      with dual-source computed tomographic coronary angiography.

PMID- 19154869
TI  - False aneurysm after transapical aortic valve implantation.

PMID- 19154870
TI  - Extralobar pulmonary sequestration infected with Mycobacterium gordonae.

PMID- 19154871
TI  - Intrapulmonary psammomatous melanotic schwannoma.

PMID- 19154872
TI  - Low-grade sarcoma of the right upper lobe vein mimicking a metastatic disease.

PMID- 19154873
TI  - Lipomatous septal hypertrophy.

PMID- 19154874
TI  - Surgical approach to repair of ruptured chordae tendineae causing tricuspid
      regurgitation.

PMID- 19154875
TI  - Is subtotal resection of a right ventricular fibroma a valid surgical option?

PMID- 19154876
TI  - Simultaneous repair for aortic incompetence with annuloaortic ectasia and pectus
      excavatum by modified Ravitch procedure with pectus bars in an adult patient with
      Marfan syndrome.

PMID- 19154877
TI  - Mitral valve repair during bypass in a 4-year-old girl with familial Evans
      syndrome.

PMID- 19154878
TI  - Ruptured aneurysm of the sinus of Valsalva protruding into the pulmonary artery.

PMID- 19154879
TI  - Mechanical support for acute right ventricular failure: evolving surgical
      paradigms.

PMID- 19154880
TI  - Takotsubo cardiomyopathy after repair of ruptured abdominal aortic aneurysm.

PMID- 19154881
TI  - Successful cardiac transplant after Berlin Heart bridge in a single ventricle
      heart: use of aortopulmonary shunt as a supplementary source of pulmonary blood
      flow.

PMID- 19154882
TI  - Modified perfusion technique for patients with renal cell carcinoma infiltrating
      the inferior vena cava.

PMID- 19154883
TI  - Latero-lateral slide tracheoplasty for upper airway stenosis: an 8-year follow
      up.

PMID- 19154884
TI  - A novel technique for bronchopleural fistula closure: an hourglass-shaped stent.

PMID- 19154885
TI  - A new technique for continuous intercostal-intrapleural analgesia in
      videothoracoscopic surgery.

PMID- 19154886
TI  - A simple correction for anomalous coronary arteries in adults.

PMID- 19154887
TI  - Preoperative statin therapy reduces postoperative all-cause mortality in cardiac
      surgery: a meta-analysis of controlled studies.

PMID- 19154888
TI  - Stenting versus coronary artery bypass grafting for unprotected left main
      coronary artery disease: a meta-analysis of comparative studies.

PMID- 19154889
TI  - Demand dynamic biogirdling: ten-year results.

PMID- 19154890
TI  - Do statins delay the progression of aortic stenosis?

PMID- 19154891
TI  - Cardiothoracic surgery: a specialty divided or as one.

PMID- 19154892
TI  - Esophagectomy volume threshold as a criterion for centers of excellence:
      causation or cause, strategy or strategem?

PMID- 19154893
TI  - Point: Clinical stage IA non-small cell lung cancer determined by computed
      tomography and positron emission tomography is frequently not pathologic IA non
      small cell lung cancer: the problem of understaging.
AB  - OBJECTIVE: There is an increase in interest in limited resection for clinical
      stage IA non-small cell lung cancer. The purpose of this study was to evaluate
      the accuracy of the diagnosis of clinical stage IA non-small cell lung cancer
      when determined by both computed tomography and positron emission tomography
      scans and to determine factors associated with understaging. METHODS: A
      retrospective review of a prospectively maintained database of patients with non
      small cell lung cancer was performed. Patients with clinical stage IA cancer
      determined by preoperative computed tomography and positron emission tomography
      scan were reviewed. The influence of the following factors was analyzed with
      regard to accuracy of clinical staging: tumor size, location, histology, and
      positron emission tomography positivity. RESULTS: Of the 266 patients identified,
      cancer was correctly staged in 65%. Final pathologic stages also included IB
      (15%), IIA (2.6%), IIB (4.1%), IIIA (4.9%), IIIB (7.5%), and IV (.08%). Positive
      lymph nodes were found in 11.7% of patients. Pathologic T classification changed
      in 28.2% of patients. Cancer in patients with clinical tumor size greater than 2
      cm (n = 68) was significantly more likely to be understaged than in patients with
      tumors 2 cm or less (49% vs 29%, P = .003). Cancer in patients with a positron
      emission tomography-positive (positron emission tomography +VE) primary
      evaluation (n = 218) was also more likely to be understaged (39% vs 15%, P =
      .001). Of patients with positron emission tomography +VE tumors greater than 2
      cm, cancer was clinically understaged in 55%, compared with 32% for positron
      emission tomography +VE tumors 2 cm or less, and only 17% for positron emission
      tomography negative (-VE) tumors less than 2 cm. CONCLUSION: Clinical stage IA
      lung cancer is frequently understaged in patients. Size greater than 2 cm and
      positron emission tomography positivity are risk factors for understaging.
      Limited resection should be undertaken with caution in such patients.

PMID- 19154894
TI  - Counterpoint: Despite staging inaccuracies, patients with non-small cell lung
      cancer are best served by having integrated positron emission tomography/computed
      tomography before therapy.

PMID- 19154895
TI  - The effect of volume on esophageal cancer resections: what constitutes acceptable
      resection volumes for centers of excellence?
AB  - OBJECTIVE: Volume-outcome relationships for esophageal cancer resection have been
      well described with centers of excellence defined by volume. No consensus exists
      for what constitutes a "high-volume" center. We aim to determine if an objective
      evidence-based threshold of operative volume associated with improvement in
      operative outcome for esophageal resections can be defined. METHODS:
      Retrospective analysis was performed on patients undergoing esophageal resection
      for cancer in the 1998 to 2005 Nationwide Inpatient Sample. A series of
      multivariable analyses were performed, changing the resection volume cutoff to
      account for the range of annual hospital resections. The goodness of fit of each
      model was compared by pseudo r(2), the amount of data variance explained by each
      model. RESULTS: A total of 4080 patients underwent esophageal resection. The
      median annual hospital resection volume was 4 (range: 1-34). The mortality rate
      of "high-volume" centers ranged from 9.94% (>or=2 resection/year) to 1.56%
      (>or=30 resections/year). The best model was with an annual hospital resection
      volume greater than or equal to 15 (3.87% of data variance explained). The
      difference in goodness of fit between the best model and other models with
      different volume cutoffs was 0.64%, suggesting that volume explains less than 1%
      of variance in perioperative death. CONCLUSION: Our data do not support the use
      of volume cutoffs for defining centers of excellence for esophageal cancer
      resections. Although volume has an incremental impact on mortality, volume alone
      is insufficient for defining centers of excellence. Volume seems to function as
      an imperfect surrogate for other variables, which may better define centers of
      excellence. Additional work is needed to identify these variables.

PMID- 19154897
TI  - A thoracic surgery clinic dedicated to indeterminate pulmonary nodules: too many
      scans and too little pathology?
AB  - OBJECTIVE: Widespread application of computed tomographic scans has increased
      detection of asymptomatic pulmonary nodules. A dedicated clinic was established
      to encourage referral and manage large numbers of patients with such nodules.
      METHODS: Patients were evaluated periodically by a nurse practitioner with
      surgeon oversight, and follow-up imaging was centralized. Patients were rescanned
      at intervals on the basis of radiologist recommendation. RESULTS: A total of 414
      patients, 189 male and 225 female with a median age of 60.2 years (20.7-84.1
      years), were evaluated since April 2000. Median follow-up was 1.51 years (0-6.65
      years). Thirty-seven percent (153/414) were older than 60 years with at least 10
      pack-years of tobacco use, whereas 30% (123/414) had never smoked. A total of 286
      patients completed at least 2 years of follow-up computed tomographic evaluation.
      After 2 years, 24.2% (69/286) were deemed in stable condition and were discharged
      from further follow-up, whereas 22.4% (64/286) of patients were followed up
      longer than 2 years owing to the development of new nodules. Forty-five percent
      (127/286) of patients did not complete their recommended follow-up at our clinic.
      Overall, 3% (13/414) of our patients have been shown to have a malignant tumor.
      Only 5 patients underwent curative resection of a primary lung cancer.
      CONCLUSION: In a population of patients with indeterminate nodules in routine
      clinical practice, few patients required intervention and few cancers were
      detected. Although the benefits of a "nodule" clinic may include patient
      reassurance and convenience to referring physicians, a significant number of
      patients did not complete their follow-up in our clinic.

PMID- 19154899
TI  - Health-related quality of life in esophageal cancer: effect of neoadjuvant
      chemoradiotherapy followed by surgical intervention.
AB  - OBJECTIVE: We sought to determine the effect of neoadjuvant chemoradiotherapy
      followed by surgical intervention on health-related quality of life in patients
      with esophageal cancer. METHODS: Health-related quality of life was evaluated in
      a prospective phase II study of neoadjuvant chemoradiotherapy followed by
      esophagectomy in 52 patients with carcinoma of the esophagus. Esophagectomy was
      performed 6 weeks after completion of induction. Functional Assessment of Cancer
      Therapy-Esophageal scoring was performed before treatment, 7 weeks after
      initiation of neoadjuvant therapy, before resection, and at 1, 3, and 6 months
      and 1 year after resection. RESULTS: Forty-three patients completed the entire
      treatment protocol. Functional Assessment of Cancer Therapy-Esophageal scores
      decreased significantly after chemoradiation at week 7 (120 vs 127 at baseline, P
      = .04) but returned to baseline levels before surgical intervention (127).
      Similarly, scores decreased significantly after surgical intervention (115 at 1
      month, P = .02) but returned to baseline levels by 3 months postoperatively
      (127). At 1 year postoperatively, there was a statistically significant
      improvement in scores compared with those at baseline (139, P = .003). Functional
      Assessment of Cancer Therapy-Esophageal scores continued to increase over time
      for patients who were alive at least 1 year after the operation with or without
      disease but were observed to significantly decrease in those who died within 1
      year after the operation (P = .0001). An increase in quality of life was
      associated with a significantly lower risk of death (P = .04). CONCLUSION:
      Neoadjuvant therapy has a significant effect on health-related quality of life,
      but this is transient, with recovery to baseline within 5 to 7 weeks after
      completion of induction therapy. Health-related quality of life decreases again
      after surgical intervention but returns to baseline levels within 3 months.

PMID- 19154901
TI  - Fluorodeoxyglucose positron emission tomography and tumor marker expression in
      non-small cell lung cancer.
AB  - OBJECTIVE: The best current noninvasive surrogate for tumor biology is
      fluorodeoxyglucose positron emission tomography (FDG-PET). Both FDG-PET maximal
      standardized uptake values and selected tumor markers have been shown to
      correlate with stage, nodal disease, and survival in non-small cell lung cancer
      (NSCLC). However, there are limited data correlating FDG-PET with tumor markers.
      The purpose of this study was to determine the correlation of tumor marker
      expression with FDG-PET maximal standardized uptake values in NSCLC. METHODS: FDG
      PET maximal standardized uptake values were calculated in patients with NSCLC (n
      = 149). No patient had induction chemoradiotherapy. Intraoperative NSCLC tissue
      was obtained and tissue microarrays were created. Immunohistochemical analysis
      was performed for 5 known NSCLC tumor markers (glucose transporter 1, p53, cyclin
      D1, epidermal growth factor receptor, and vascular endothelial growth factor).
      Each tumor marker was assessed independently by two pathologists using common
      grading criteria. Subgroup analysis based on histologic characteristics and
      regional nodal status was performed. RESULTS: FDG-PET correlated with T
      classification (P < .0001), N stage (P = .002), and greatest tumor dimension (P <
      .0001). In addition, increasing maximal standardized uptake values correlated
      with increased expression of glucose transporter 1 (P < .0001) and p53 (P = .04)
      in adenocarcinoma. Epidermal growth factor receptor expression correlated with
      maximal standardized uptake values without predilection for histologic subtype (P
      = .004). CONCLUSION: FDG-PET maximal standardized uptake values correlate with an
      increased expression of glucose transporter 1 and p53 in lung adenocarcinoma, but
      not squamous cell cancer. Future studies attempting to correlate FDG-PET with
      tumor biology will need to consider the effect of different tumor histologic
      types.

PMID- 19154902
TI  - Salvage esophagectomy after high-dose chemoradiotherapy for esophageal squamous
      cell carcinoma.
AB  - OBJECTIVE: Chemoradiotherapy is a popular definitive therapy for esophageal
      carcinoma among many patients and oncologists. Although the complete response
      rates are high and short-term survival is favorable after chemoradiotherapy,
      persistent or recurrent locoregional disease is frequent. Salvage surgery is the
      sole curative intent treatment option for this course of the disease. The present
      study evaluates the safety and value of salvage esophagectomy for locoregional
      failure after high-dose definitive chemoradiotherapy for esophageal squamous cell
      carcinoma. METHODS: We reviewed 59 consecutive patients with thoracic esophageal
      squamous cell carcinoma who underwent salvage esophagectomy after definitive
      chemoradiotherapy. All patients received more than 60 Gy of radiation plus
      concurrent chemotherapy for curative intent. The data were compared with those of
      patients who received esophagectomy without preoperative therapy. RESULTS:
      Postoperative morbidity and mortality rates were increased among patients who
      underwent salvage esophagectomy compared with those who underwent esophagectomy
      without preoperative therapy (mean hospital stay, 38 vs 33 days; anastomotic leak
      rates, 31% vs 25%; respiratory complication rates, 31% vs 20%; reintubation
      within 1 week, 2% vs 2%; hospital mortality rates, 8% vs 2%). Tracheobronchial
      necrosis and gastric conduit necrosis were highly lethal complications after
      salvage esophagectomy; 3-year postoperative survivals were 38% and 58%,
      respectively. CONCLUSION: Patients who underwent salvage esophagectomy after
      definitive high-dose chemoradiotherapy had increased morbidity and mortality.
      Nevertheless, this is acceptable in view of the potential long-term survival
      after salvage esophagectomy. Such treatment should be considered for carefully
      selected patients at specialized centers.

PMID- 19154903
TI  - Factors predictive of prognosis after esophagectomy for squamous cell cancer.
AB  - OBJECTIVE: To evaluate the prognosis after esophagectomy for squamous cell
      carcinoma of the thoracic esophagus and its prognostic factors. METHODS: Six
      hundred five patients with primary squamous cell carcinoma of the thoracic
      esophagus who underwent curative esophagectomy between June 1997 and June 1998
      were collected from 3 medical centers. Among them, 26 patients died from the
      operation and 26 patients did not complete adjuvant treatment owing to toxicity.
      Univariate and multivariate analysis was performed to identify prognostic factors
      for survival. The effect of adjuvant treatment on survival was also evaluated.
      RESULTS: The 1-, 3-, 5-, and 10-year overall survivals of 605 patients were 90%,
      65%, 36%, and 8%, respectively. Multivariate analysis identified the following as
      independent prognostic factors: number of lymph node metastases (P < .001),
      histologic differentiation (P < .001), tumor location (P = .002), depth of
      invasion (P = .020), and vascular invasion (P = .023). CONCLUSIONS: Several
      pathologic characteristics of the primary tumor are correlated with the outcome
      of esophagectomy for squamous carcinoma of the thoracic esophagus. Patients with
      fewer than 2 metastatic nodes after curative esophagectomy have a better
      prognosis than those with multiple involved nodes (>2). To stratify patients
      appropriately for prognosis, it is necessary to refine the current 6th edition
      TNM staging system.

PMID- 19154904
TI  - The impact of placing multiple grafts to each myocardial territory on long-term
      survival after coronary artery bypass grafting.
AB  - OBJECTIVE: Incomplete myocardial revascularization decreases survival for
      patients undergoing coronary artery bypass grafting. The effects of constructing
      multiple grafts to each major diseased artery territory are unknown. We aimed to
      determine the impact on long-term survival after coronary artery bypass grafting
      of placing multiple grafts to each myocardial territory. METHODS: We reviewed
      data from 1129 consecutive patients who underwent coronary artery bypass grafting
      at our institution between 1997 and 2007 and compared outcomes between patients
      who received multiple grafts to each major diseased artery territory (n = 549)
      with those of patients who received single grafts to each territory (n = 580). We
      assessed long-term survival with Kaplan-Meier curves generated by log-rank tests,
      adjusting for confounding factors with Cox proportional hazards regression
      analysis. RESULTS: Patients who received multiple grafts to each major diseased
      artery territory had longer cardiopulmonary bypass and aortic crossclamp times
      than patients who received single grafts per territory. Patient groups had
      similar early outcomes, including 30-day mortalities (1.3% vs 1.4%, P > .999) and
      incidences of major adverse cardiac events (2.9% vs 2.2%, P = .57). Cox
      regression 10-year survival curves were also similar between groups (adjusted
      hazard ratio 0.94, 95% confidence interval 0.67-1.34, P = .74). CONCLUSION:
      Patients who received multiple grafts to each major diseased artery territory had
      early outcomes similar to those who received single grafts per territory.
      Constructing multiple grafts to each major diseased artery territory increases
      operative time and does not improve long-term survival.

PMID- 19154905
TI  - Improved quality and cost-effectiveness of coronary artery bypass grafting in the
      United States from 1988 to 2005.
AB  - OBJECTIVE: This study was undertaken to assess the impact of increasing patient
      complexity and health care cost on coronary artery bypass grafting quality and
      cost-effectiveness in the United States over an 18-year period. METHODS: A
      retrospective study was carried out utilizing the Nationwide Inpatient Sample to
      track the characteristics and outcomes of 5,549,700 patients having isolated
      coronary artery bypass grafting in the United States from 1988 to 2005. Expected
      mortality, risk-adjusted mortality, and hospital charges were tracked over this
      period. RESULTS: The prevalence of congestive heart failure, pulmonary disease,
      diabetes, and acute myocardial infarction increased significantly over the study
      period. Expected mortality increased from 2.57% to 3.66%, reflecting the
      increasing patient comorbidity burden (P < .0001). Despite this, coronary artery
      bypass grafting outcomes improved, leading to a decrease in risk-adjusted
      mortality from 6.20% to 2.12% (P < .0001). Furthermore, when hospital charges
      were corrected for medical care inflation, hospital charges declined
      significantly, from $26,210 in 1988 to $19,196 in 2005 (1988 dollars, P < .0001).
      CONCLUSIONS: Coronary artery bypass grafting surgery is being performed on an
      increasingly complex, high-risk patient population in the United States. Despite
      this challenge, risk-adjusted operative mortality has progressively declined.
      Moreover, hospital charges for coronary artery bypass grafting in relation to
      other medical care services have been reduced. These findings reflect improved
      quality and cost-effectiveness of coronary artery bypass grafting in the United
      States. Ongoing efforts directed at quality improvement should address the risks
      associated with comorbidities that increasingly accompany the diagnosis of
      coronary artery disease in patients having coronary artery bypass grafting.

PMID- 19154906
TI  - Early and late outcomes in minimally invasive mitral valve repair: an eleven-year
      experience in 707 patients.
AB  - OBJECTIVE: This study analyzes a single institution experience with minimally
      invasive mitral valve repair and evaluates long-term surgical outcomes of
      morbidity, mortality, and rates of reoperation. Late follow-up of mitral
      regurgitation and left ventricular function were also assessed. METHODS: Between
      August 1996 and October 2007, minimally invasive mitral valve repair was
      performed in 713 patients (mean follow-up 5.7 years). Excluding 6 repairs with
      robotic assistance, an perspective analysis of the remaining 707 patients was
      carried forth. Mean age was 57 +/- 13 years. Mean preoperative ejection fraction
      was 60% +/- 10%. Surgical access was through a lower ministernotomy (74%), right
      parasternal incision (24%), right thoracotomy (1.4%), or upper ministernotomy
      (0.7%). Exposure of the mitral valve was through the left atrium in 58% of the
      cases and transeptal in 42%. A ring annuloplasty was incorporated into 680 (96%)
      of 707 repairs. The Kaplan-Meier and Student t test for paired samples were used
      for statistical analysis. RESULTS: There were 3 (0.4%) operative deaths.
      Perioperative morbidity included new-onset atrial fibrillation (20%), reoperation
      for bleeding (2%), stroke (1.9%), permanent pacemaker implantation (1.7%), deep
      sternal wound infection (0.7%), and aortic dissection (0.4%). Median hospital
      stay was 5 days. Only 31% of patients required blood transfusion during the
      hospital course. There were 49 (6.9%) late deaths and 34 (4.8%) failed repairs
      necessitating reoperation. At 11.2 years, survival was 83% (95% confidence
      intervals, 76.5-88.1); freedom from reoperation was 92% (95% confidence
      intervals, 86.2-94.9). Nine (1.3%) patients were lost to follow-up. A total of
      2369 patient-years of echocardiography time were obtained in 544 patients (mean
      4.36 years, range 0.47-11.09). Mean grade of mitral regurgitation decreased from
      3.80 to 1.42 (P < .0001) Mean left ventricular ejection fraction decreased from
      60.7% to 56.3% (P < .0001). Combined risk of death, reoperation, and recurrence
      of moderately severe to severe mitral regurgitation was 7.7% (43/555).
      CONCLUSION: Minimally invasive mitral valve repair is safe, with low
      perioperative morbidity, low rates of recurrent mitral regurgitation, and low
      rates of reoperation and death at late follow-up.

PMID- 19154907
TI  - A 20-year experience of 1712 patients with the Biocor porcine bioprosthesis.
AB  - OBJECTIVE: The 20-year data from the ongoing long-term study of the St Jude
      Medical Biocor (St Jude Medical, St Paul, Minn) porcine bioprosthesis are
      reported. Earlier follow-ups have shown that the valve has excellent durability.
      After 20 years, will this continue to be true? METHODS: Data were obtained for
      1712 patients who underwent valve replacement (1518 aortic valve replacements;
      194 mitral valve replacements) with glutaraldehyde-preserved Biocor bioprostheses
      at Sahlgrenska University Hospital (Sweden) between 1983 and 2003. Follow-up
      after surgery was evaluated on alternate years using hospital records,
      interviews, and questionnaires. RESULTS: At 20 years, the cumulative follow-up
      was 8843 and 1195 patient-years for aortic valve replacement and mitral valve
      replacement, respectively. Survival after aortic valve replacement was 17.7% +/-
      3.3%, and survival after mitral valve replacement was 16.4% +/- 4.7%. Actuarial
      freedom from reoperation because of structural valve deterioration was 61.1% +/-
      8.5% and 79.3% +/- 6.0% after aortic valve replacement and mitral valve
      replacement, respectively. (The equivalent actual/cumulative values were 85.6% +/
      2.2% and 91.2% +/- 2.6%, respectively.) In aortic valve recipients aged 65 years
      or less and more than 65 years, actuarial freedom from reoperation because of
      structural valve deterioration was 44.5% +/- 9.2% and 92.1% +/- 3.9%,
      respectively. The equivalent values in mitral valve recipients were 75.2% +/-
      7.6% and 88.0% +/- 8.1%, respectively. CONCLUSION: The 20-year data confirm the
      excellent valve durability reported at the 17-year follow-up after both aortic
      valve replacement and mitral valve replacement using the Biocor porcine
      bioprosthesis.

PMID- 19154908
TI  - Isolated aortic valve replacement in North America comprising 108,687 patients in
      10 years: changes in risks, valve types, and outcomes in the Society of Thoracic
      Surgeons National Database.
AB  - OBJECTIVE: More than 200,000 aortic valve replacements are performed annually
      worldwide. We describe changes in the aortic valve replacement population during
      10 years in a large registry and analyze outcomes. METHODS: The Society of
      Thoracic Surgeons National Database was queried for all isolated aortic valve
      replacements between January 1, 1997, and December 31, 2006. After exclusion for
      endocarditis and missing age or sex data, 108,687 isolated aortic valve
      replacements were analyzed. Time-related trends were assessed by comparing
      distributions of risk factors, valve types, and outcomes in 1997 versus 2006.
      Differences in case mix were summarized by comparing average predicted mortality
      risks with a logistic regression model. Differences across subgroups and time
      were assessed. RESULTS: There was a dramatic shift toward use of bioprosthetic
      valves. Aortic valve replacement recipients in 2006 were older (mean age 65.9 vs
      67.9 years, P < .001) with higher predicted operative mortality risk (2.75 vs
      3.25, P < .001); however, observed mortality and permanent stroke rate fell (by
      24% and 27%, respectively). Female sex, age older than 70 years, and ejection
      fraction less than 30% were all related to higher mortality, higher stroke rate
      and longer postoperative stay. There was a 39% reduction in mortality with
      preoperative renal failure. CONCLUSIONS: Morbidity and mortality of isolated
      aortic valve replacement have fallen, despite gradual increases in patient age
      and overall risk profile. There has been a shift toward bioprostheses. Women,
      patients older than 70 years, and patients with ejection fraction less than 30%
      have worse outcomes for mortality, stroke, and postoperative stay.

PMID- 19154909
TI  - Incidence of thromboembolic complications in patients with mechanical heart
      valves with a subtherapeutic international normalized ratio.
AB  - OBJECTIVE: Subtherapeutic international normalized ratios are frequently
      encountered in clinical practice, and patients with mechanical heart valves with
      inadequate anticoagulation may be exposed to an increased risk of thromboembolic
      events. There are no data on thromboembolic event risk for these patients.
      METHODS: We assessed the current practice patterns in the management of patients
      with mechanical heart valves with subtherapeutic international normalized ratios
      and assessed the risk of thromboembolic complications in this setting. The charts
      of patients with mechanical heart valves followed up in two anticoagulation
      clinics were reviewed. Patients with a history of stable, therapeutic
      anticoagulation but with a subtherapeutic international normalized ratio were
      included. Patients who underwent invasive procedures requiring temporary
      suspension of antithrombotic therapy were excluded. Data on use and dose of low
      molecular weight heparin bridging therapy were collected. RESULTS: The incidence
      of objectively confirmed thromboembolic events within 90 days after obtaining the
      index international normalized ratio was assessed. Two hundred ninety-four
      patients with mechanical heart valves were included (mean age 63.3 years, 47.3%
      male). Low-molecular weight heparin was prescribed in 14 cases (4.8%). At 90
      days, 1 patient had a thromboembolic complication (0.3%, 95% confidence interval
      0%-1.9%). CONCLUSION: Patients with previously stable, therapeutic
      anticoagulation with a subtherapeutic international normalized ratio have a low
      risk of thromboembolic events. Withholding low-molecular weight heparin bridging
      therapy is a reasonable therapeutic option in these cases.

PMID- 19154910
TI  - Postimplantation morphologic changes of glutaraldehyde-fixed porcine aortic roots
      and risk of aneurysm and rupture.
AB  - OBJECTIVE: Rupture of glutaraldehyde-fixed porcine aortic roots has been
      reported, but the mechanism and incidence of this complication is unknown. This
      study evaluates the clinical outcomes and the risk of dilation and rupture of
      porcine aortic roots after implantation. METHODS: Commercially available porcine
      aortic roots were used for aortic root replacement in 308 patients (Freestyle
      bioprosthesis [Medtronic, Minneapolis, Minn] in 251 patients and Toronto Root [St
      Jude Medical, St Paul, Minn] in 57 patients) whose mean age was 62 +/- 13 years.
      The main indication for aortic root replacement was dilation of the native aortic
      root. Clinical follow-up was complete at a mean of 5.3 +/- 2.5 years. Valve
      function and aortic root diameter were assessed by means of echocardiography.
      RESULTS: There were 10 (3.2%) operative and 39 (12.6%) late deaths. At 8 years,
      patients' survival was 79.0% +/- 3.1%, freedom from reoperation was 95.3% +/-
      1.7%, and freedom from severe aortic insufficiency was 93.8% +/- 2.7%. The
      diameter of the aortic sinuses increased from 31.9 +/- 4.3 to 34.1 +/- 4.8 mm (P
      < .0001), and it exceeded 40 mm in 10% of the patients. Linear regression
      analysis revealed that the duration of follow-up (P < .0001) and the size of the
      valve implanted (P < .0001) were associated with risk of sinus dilation. There
      was only 1 early rupture of the noncoronary aortic sinus and 2 late aneurysms
      that required repeat operations. Histologic examination of explanted aneurysmal
      porcine roots revealed marked changes in the xenograft arterial wall, with
      abundant mononuclear cells suggestive of immunologic reaction. CONCLUSIONS: Mild
      dilation of porcine aortic roots after aortic root replacement is common, but
      aneurysm formation and rupture are rare during the first decade of follow-up.
      Annual surveillance with echocardiography is recommended.

PMID- 19154911
TI  - Ascending thoracic aortic aneurysms are associated with compositional remodeling
      and vessel stiffening but not weakening in age-matched subjects.
AB  - OBJECTIVE: We sought to examine in age-matched subjects the biomechanical and
      compositional remodeling associated with ascending thoracic aortic aneurysms
      according to region and direction. METHODS: Whole, fresh, degenerative ascending
      thoracic aortic aneurysms were taken from 26 patients (age, 69 +/- 2 years;
      maximum aortic diameter, 5.9 +/- 0.3 cm) during elective surgical intervention,
      and 15 nonaneurysmal ascending thoracic aortas were obtained during autopsies
      (age, 66 +/- 3 years; maximum aortic diameter, 3.3 +/- 0.2 cm). These were cut
      into anterior, right lateral, posterior, and left lateral regions, and
      circumferentially and longitudinally oriented specimens were prepared. The aortic
      specimens were submitted to histomorphometric and biomechanical studies,
      including measurement of failure strain (ie, extensibility), failure stress (ie,
      strength), and peak elastic modulus (ie, stiffness). RESULTS: Wall elastin, but
      not collagen content, decreased in aneurysmal specimens, displaying lower wall
      thickness and failure strain, higher peak elastic modulus, and equal failure
      stress than control specimens in the majority of regions and directions. Similar
      differences were noted in pooled data from all regions. Regional variations in
      mechanical parameters were mostly found in longitudinally oriented tissue.
      Circumferential specimens showed higher failure stress and peak elastic modulus
      but equal failure strain than longitudinal specimens. CONCLUSIONS: Our findings
      contradict previous studies on ascending thoracic and abdominal aortic aneurysms,
      suggesting that the former might not cause weakening but rather only stiffening
      and reduction in tissue extensibility and elastin content. Marked heterogeneity
      was evident in healthy and aneurysmal aortas. The present data offer insight into
      the pathogenesis of aneurysm dissection. Information on directional and regional
      variations is pertinent because dissections develop circumferentially and bulging
      preferentially occurs in the anterior region.

PMID- 19154912
TI  - Outcomes of surgical intervention for isolated active mitral valve endocarditis.
AB  - OBJECTIVE: Although several studies have examined the outcomes of mitral valve
      repair for infective endocarditis, no studies have documented the long-term
      outcomes of surgical intervention for active endocarditis confined to the mitral
      valve. METHODS: One hundred four patients underwent surgical intervention for
      active infective endocarditis confined to the mitral valve over a 27-year period
      (mean age, 50 +/- 18 years; 52% female). The infected valve was native in 81
      patients, previously repaired 6 patients, and prosthetic in 17 patients.
      Staphylococcus aureus was the most commonly isolated (32%) source of infection.
      Twenty-eight (27%) patients had annular abscesses. Surgical intervention
      consisted of valve repair or replacement for limited infection and radical
      resection, annular patch reconstruction, and valve replacement for annular
      abscess. Mean follow-up was 5.6 +/- 4.4 years (range, 0-20 years) and was
      complete. RESULTS: There were 9 (8.7%) in-hospital deaths and 28 (27%) late
      deaths. Overall survival at 5, 7, and 10 years was 73% +/- 5%, 68% +/- 5%, and
      58% +/- 6%, respectively. At 7 years, freedom from recurrent endocarditis was 89%
      +/- 4% and freedom from reoperation was 94% +/- 3%. Event-free survival at 7 and
      10 years was 60% +/- 6% and 46% +/- 7%, respectively, and was significantly
      higher in patients with native endocarditis versus those with nonnative
      endocarditis (ie, prosthetic or previously repaired; 7 years: 63% +/- 7% vs 50%
      +/- 12%, P < .005). Preoperative shock, S aureus infection, and bioprosthesis
      insertion were independent predictors of death from all causes. The patients in
      the bioprosthesis group were older (57 +/- 20 years vs 44 +/- 15 years in the
      mechanical group and 46 +/- 12 years in the repair group, P = .003). CONCLUSIONS:
      Surgical intervention for isolated active mitral valve endocarditis remains
      difficult, with high morbidity and mortality in the long term. Event-free
      survival is worse in those who have nonnative mitral valve endocarditis.

PMID- 19154913
TI  - Endovascular repair of the thoracic aorta in the post-FDA approval era.
AB  - OBJECTIVE: Endovascular repair of thoracic aortic disease is rapidly progressing
      as an alternative to open surgical therapy. In March of 2005, the Gore TAG
      thoracic endoprosthesis (W. L. Gore & Associates, Inc, Flagstaff, Ariz) received
      Food and Drug Administration (FDA) approval for the treatment of descending
      thoracic aortic aneurysms. Subsequently, off-label use of the technology expanded
      to include additional thoracic aortic diseases. The purpose of this study was to
      examine whether the outcomes with this device changed after the inclusion and
      exclusion criteria of FDA-controlled trials no longer governed patient selection.
      METHODS: A retrospective analysis was performed on all patients who underwent
      endovascular repair of the thoracic aorta with the Gore TAG device at our
      institution between March 23, 2005, and September 8, 2006. RESULTS: Fifty
      consecutive patients with a broad range of aortic pathologic conditions were
      included in the study. The results in this group compared with those of the phase
      II trial included the following: length of stay, 7.5 versus 7.6 days (P = .97);
      intensive care unit stay, 3.7 versus 2.6 days (P = .61); 30-day mortality, 2.0%
      versus 1.5% (P = .68); spinal cord injury, 2% versus 3% (P = .89); stroke, 4%
      versus 4% (P = .67); early endoleaks, 26% versus 4% (P < .01); and late
      endoleaks, 18% versus 7% (P = .08). At 1 year, overall survival was 92% compared
      with 82% in the phase II trial. CONCLUSIONS: In the post-FDA approval era,
      endovascular stent-graft therapy is frequently applied to patients with more
      challenging thoracic aortic anatomy and a wide range of pathologic conditions.
      Our results in this group are similar to outcomes reported for patients with
      descending thoracic aortic aneurysm exclusively.

PMID- 19154914
TI  - Ten-year experience with handmade trileaflet polytetrafluoroethylene valved
      conduit used for pulmonary reconstruction.
AB  - OBJECTIVE: The objective of this study was to investigate the results of handmade
      polytetrafluoroethylene trileaflet conduits implanted in the pulmonary position
      since 1997. METHODS: One hundred thirty-nine patients underwent pulmonary
      reconstruction with a polytetrafluoroethylene conduit. Conduit function was
      investigated by means of review of serial echocardiographic studies. RESULTS:
      Mean age and body weight were 12.7 +/- 12.0 years and 30.9 +/- 20.6 kg. Mean size
      of the conduit was 21.0 +/- 3.8 mm (12-28 mm). The z score of the conduit was
      +0.5 +/- 0.8 for patients older than 15 years (n = 43), +1.2 +/- 0.7 for patients
      5 to 15 years old (n = 48), and +2.4 +/- 0.5 for patients younger than 5 years (n
      = 48). Conduits were used for the Ross procedure in 21 patients and for repair of
      complex congenital heart disease in 118 patients. There were 3 (2.2%) in-hospital
      deaths and 1 late death. Four patients required conduit explantation because of
      pulmonary artery distortion at a distal anastomotic site (interval, 1.2 years),
      infection of the polytetrafluoroethylene valve (interval, 1.6 years), midportion
      angulation of the conduit (interval, 4.9 years), and conduit compression by the
      ascending aorta (interval, 5.4 years). Estimated freedom from conduit
      explantation was 88.0% +/- 6.8%, and pulmonary insufficiency was less than or
      equal to mild in 75.0% at 10 years. All valves maintained their motion, and the
      mean estimated pressure gradient across the conduit was 19.6 +/- 11.9 mm Hg at 5
      years and appeared to reach a plateau thereafter. The pressure gradient across
      the conduit was 14.2 +/- 8.0 mm Hg at 3 years (P = .0127) and 18.1 +/- 7.5 mm Hg
      at 7 years (P = .0208). CONCLUSIONS: Polytetrafluoroethylene conduits represent a
      valid option and reliable alternative to homograft and xenograft implantation for
      pulmonary reconstruction.

PMID- 19154915
TI  - Morphologic features of atrioventricular septal defect with only ventricular
      component: further observations pertinent to surgical repair.
AB  - OBJECTIVE: Atrioventricular septal defect with only a ventricular component of
      septal deficiency is the least common of the various forms of this malformation.
      We reviewed its morphology in heart specimens and compared our findings with the
      other forms for a better understanding of its surgical morphology. METHODS: We
      examined 78 cardiac specimens with atrioventricular septal defect; 56 (72%) had
      common atrioventricular valve orifice with both atrial and ventricular components
      (so-called "complete" form), and 22 (28%) had separate valve orifices (so-called
      "partial" or "incomplete" form) with 17 having only an atrial component (so
      called "ostium primum" form) and 5 having only a ventricular component. RESULTS:
      Among hearts with atrioventricular septal defect, the hearts with only
      ventricular component of the defect had the mildest deformity of the ventricular
      mass, characterized by less inlet-outlet disproportion, smaller "gap" between
      anterior and posterior parts of the atrioventricular junction, and the least
      extensive septal deficiency. However, these hearts still possessed the
      characteristic common atrioventricular junction and had 5-leaflet configuration
      of the atrioventricular valve with similar proportions of mural leaflets in both
      valve orifices, as in other forms. Furthermore, owing to the unique relationship
      of the bridging leaflets to the septum, the leaflets were always "upwardly"
      displaced as opposed to "downwardly" displaced leaflets in "ostium primum" form.
      CONCLUSIONS: Our observations suggest this entity might represent the mildest end
      of the whole spectrum of hearts with atrioventricular septal defect. Since
      "upwardly" displaced leaflets are not modifiable and could be aggravated further
      after surgery, they might play a role in late valve dysfunction.

PMID- 19154916
TI  - Prospective follow-up study of children with univentricular heart:
      neurodevelopmental outcome at age 12 months.
AB  - OBJECTIVES: Despite recent advances in the treatment of children with
      univentricular heart, their neurodevelopmental outcome remains a major concern.
      METHODS: This prospective follow-up study evaluated the neurodevelopmental
      outcome of 23 patients with hypoplastic left heart syndrome, 14 with other forms
      of univentricular heart, and 46 healthy control subjects at a median age of 12.2
      months. The Griffiths Developmental Scale and Alberta Infant Motor Scale served
      for developmental evaluation. RESULTS: The mean Griffiths developmental quotient
      of children with hypoplastic left heart syndrome was significantly less (91.6)
      than that of control children (106.8, P < .001). Patients with univentricular
      heart scored significantly lower than control subjects only in the gross motor
      domain (P = .001) but not in overall development (100.6). Alberta Infant Motor
      Scale scores were significantly lower in children with hypoplastic left heart
      syndrome (37.5, P < .001) and univentricular heart (43.5, P = .011) than in
      control subjects (53.3). In linear regression a diagnosis of hypoplastic left
      heart syndrome (P = .016), a clinical history of seizure (P = .002), and the
      highest plasma lactate level after the bidirectional Glenn operation (P = .045)
      were significantly associated with the developmental quotient. CONCLUSIONS: At
      age 1 year, the level of development of children with univentricular heart was
      significantly lower than for control subjects only in motor skills, whereas
      children with hypoplastic left heart syndrome had a more widespread developmental
      delay. The diagnosis, a clinical seizure history, and increased plasma lactate
      levels after the bidirectional Glenn operation emerged as risk factors.

PMID- 19154917
TI  - Impaired neuroanatomic development in infants with congenital heart disease.
AB  - OBJECTIVES: We performed a regional volumetric study of the brain using 3
      dimensional magnetic resonance imaging in infants with congenital heart disease
      to search for variables in anatomic development of the brain that may be
      associated with functional impairment. METHODS: Forty infants with congenital
      heart disease-17 infants with single ventricle physiology, 5 with transposition
      of great arteries, and 18 with ventricular septal defect-were studied
      prospectively by 3-dimensional magnetic resonance imaging of the brain several
      months after heart surgery. RESULTS: The global volume of gray matter was
      significantly reduced in the patients with congenital heart disease compared with
      normal controls (P < .001), whereas no significant difference in the volume of
      white matter was observed. Further, the decrease in gray matter volume was more
      apparent in the frontal lobe than in the temporal lobe, especially in infants
      with single ventricle physiology or transposition of the great arteries.
      Multivariate analysis revealed that preoperative hypoxia is strongly associated
      with decreased frontal gray matter volume (P < .01), as well as a diagnosis of
      hypoplastic left heart syndrome (P < .05). Of note, frontal gray matter volume,
      which includes the motor area, correlated weakly with psychomotor developmental
      index scores (P < .01). CONCLUSIONS: Brain developmental impairment occurs in
      many infants with congenital heart disease, especially in those who have
      preoperative hypoxia and critical congenital heart disease. This quantitative
      volumetric study encourages larger scale and longitudinal follow-up to elucidate
      the significance of impaired neuroanatomic development on functional outcome.

PMID- 19154918
TI  - Near-infrared spectroscopy: what we know and what we need to know--a systematic
      review of the congenital heart disease literature.
AB  - OBJECTIVES: Neurologic dysfunction is a problem in patients with congenital heart
      disease. Near-infrared spectroscopy may provide a real-time window into cerebral
      oxygenation. Enthusiasm for near-infrared spectroscopy has increased hopes of
      reducing neurologic dysfunction. However, potential gains need to be evaluated
      relative to cost before routine implementation. Responding to data in ways that
      seem intuitively beneficial can be risky when the long-term impact is unknown.
      Thus, we performed a systematic review of the literature on near-infrared
      spectroscopy in congenital heart disease. METHODS: A literature search from 1950
      to April 2007 for near-infrared spectroscopy in congenital heart disease was
      undertaken. We identified 54 manuscripts and?13 reviews. RESULTS: There were 47
      case series, 4 randomized trials, and 3 retrospective studies. Two studies had
      postdischarge follow-up, one incorporating neurologic testing. Neither of these
      studies demonstrated a benefit. One retrospective study, which included near
      infrared spectroscopy and other intraoperative measures of cerebral perfusion,
      demonstrated a decrease in neurologic dysfunction using this combination of
      monitors. Three small studies were able to correlate near-infrared spectroscopy
      with other clinical and radiologic findings. CONCLUSIONS: Many centers, and even
      entire countries, have adopted near-infrared spectroscopy as standard of care.
      The available data suggest that multimodality monitoring, including near-infrared
      spectroscopy, may be a useful adjunct. The current literature on the use of near
      infrared spectroscopy alone, however, does not demonstrate improvement in
      neurologic outcome. The data correlating near-infrared spectroscopy findings with
      indirect measures of neurologic outcome or mortality are limited. Although near
      infrared spectroscopy has promise for measuring regional tissue oxygen
      saturation, the lack of data demonstrating improved outcomes limits the support
      for widespread implementation.

PMID- 19154919
TI  - Radiofrequency ablation for treatment of medically inoperable stage I non-small
      cell lung cancer.
AB  - OBJECTIVE: This study evaluated long-term results of radiofrequency ablation for
      medically inoperable early-stage lung cancer. METHODS: Thirty-one consecutive
      patients with biopsy-proven non-small cell lung cancer underwent 38 treatments of
      computed tomographically guided radiofrequency ablation in a 4.5-year period. All
      patients were carefully selected and deemed medically ineligible for resection by
      a multidisciplinary team. Radiofrequency ablation was performed with curative
      intent with a single or cluster cool-tip electrode. Patients were hospitalized
      for 23-hour observation. RESULTS: Treatment was complete in all cases, with no 30
      day mortality. Local recurrence was confirmed radiographically by computed
      tomography, positron emission tomography, or both after 31.5% of treatments
      (12/38). Two patients were successfully retreated for technical failures related
      to pneumothorax; 3 underwent radiotherapy with stable disease. Mean maximal
      diameter of 38 tumors treated was 2.0 +/- 1.0 cm (range 0.8-4.4 cm). After median
      follow-up of 17 +/- 11 months, 74% of patients (23/31) were alive. Three patients
      died of metastatic disease; 5 died of pneumonia remote from treatment. The 2- and
      4-year survivals were 78% and 47%, respectively. Median overall survival was 30
      months. Pneumothorax (13%), pneumonia (16%), and pleural effusion (21%), were the
      most common complications. CONCLUSIONS: Radiofrequency ablation of medically
      inoperable early-stage lung cancer in carefully selected patients yields
      encouraging midterm results without significant loss of pulmonary function. Local
      tumor progression appears related to lung tumors larger than 3 cm. Computed
      tomography and positron emission tomography need further validation for the early
      identification of local tumor progression following radiofrequency ablation.

PMID- 19154921
TI  - Transapical transcatheter aortic valve implantation: 1-year outcome in 26
      patients.
AB  - BACKGROUND: We reported the first case of successful transapical transcatheter
      aortic valve implantation in a human subject in 2005 and have now completed a 12
      month follow-up on our first 26 patients. This is, to date, the longest follow-up
      of patients undergoing transapical aortic valve implantation. METHODS: Between
      October 2005 and January 2007, 26 patients (13 female) underwent transcatheter
      transapical aortic valve implantation with either 23- or 26-mm Edwards
      Lifesciences transcatheter bioprostheses. All patients with symptomatic aortic
      stenosis were declined for conventional aortic valve replacement because of
      unacceptable operative risks and were not candidates for transfemoral aortic
      valve implantation because of poor arterial access. Clinical and
      echocardiographic follow-up was performed before discharge and at 1, 6, and 12
      months. Data from the 17 patients who survived over 12 months were used for
      comparisons of the baseline and follow-up results. RESULTS: The mean age was 80
      +/- 9 years, and the predicted operative mortality was 37% +/- 20% by using
      logistic EuroSCORE and 11% +/- 6% by using the Society of Thoracic Surgeons Risk
      Calculator. Valves were successfully implanted in all patients. Six patients died
      within 30 days (30-day mortality, 23%), and 3 patients died from
      noncardiovascular causes after 30 days (late mortality, 12%). Among patients who
      survived at least 30 days, 12-month survival was 85%. There were no late valve
      related complications. New York Heart Association functional class improved
      significantly. The aortic valve area and mean gradient remained stable at 12
      months (1.6 +/- 0.3 cm(2) and 9.6 +/- 4.8 mm Hg, respectively). CONCLUSION: Our 1
      year clinical and echocardiographic outcomes suggest that transapical
      transcatheter aortic valve implantation is a viable alternative to conventional
      aortic valve replacement in selected high-risk patients.

PMID- 19154922
TI  - Toward the development of a fully elastic mitral ring: preliminary, acute, in
      vivo evaluation of physiomechanical behavior.
AB  - OBJECTIVES: The optimal repair of functional mitral regurgitation is still
      debated. No device is able to simultaneously abolish mitral regurgitation and
      replicate natural mitral annular dynamics. We have tested a fully elastic mitral
      ring in an acute animal study with the purpose of evaluating (1) ring design and
      implantation technique, (2) elastic performance, and (3) acute effects on the
      native mitral annulus. METHODS: Ten healthy sheep underwent surgical implantation
      of mitral devices, the elastic component of which is represented by a helicoid
      metallic spring. Preimplantation and postimplantation echocardiographic parameter
      measurements to evaluate annular dynamics and ventricular function comprise
      mitral annular motion, systolic tissue Doppler imaging peak wave, transmitral
      pressure gradient, peak transmitral flow velocity, and ejection fraction.
      Postimplantation angiographic analysis allowed measurement of the mitral annular
      area and perimeter variations by means of segmentation of the radiopaque mitral
      device contour. RESULTS: No significant difference in terms of ejection fraction
      (P = .13) and systolic tissue Doppler imaging peak wave (P = .87) was found
      before and after implantation. Mitral annular motion (1.16 cm) was preserved. The
      percentage of systolic annular reduction derived from angiographic analysis was
      14.1% (range, 7.7%-19.7%) in terms of area and 7.2% (range, 4.9%-10.0%) in terms
      of perimeter. CONCLUSIONS: A mitral elastic ring, implantable by using a standard
      technique, acutely preserves mitral annular dynamics, allowing area and perimeter
      changes. Further chronic study is needed to verify the biocompatibility and
      durability of the device.

PMID- 19154923
TI  - Restoration of left ventricular geometry and improvement of left ventricular
      function in a rodent model of chronic ischemic cardiomyopathy.
AB  - OBJECTIVES: Various approaches to myocardial reconstruction have been developed
      for the treatment of congestive heart failure resulting from ischemic
      cardiomyopathy. METHODS: In this study we determined whether in situ application
      of polymers could reshape left ventricular geometry in a chronic rodent model of
      ischemic cardiomyopathy. RESULTS: We demonstrate that alginate and fibrin can
      augment left ventricular wall thickness, resulting in reconstruction of left
      ventricular geometry and improvement of cardiac function. Echocardiographic
      results at 5 weeks after injection of alginate demonstrated persistent
      improvement of left ventricular fractional shortening and prevention of a
      continued enlargement of left ventricular dimensions, whereas fibrin glue
      demonstrated no progression of left ventricular negative remodeling. There was
      increased arteriogenesis in both the alginate and fibrin glue groups compared
      with that seen in the phosphate-buffered saline control group. Infarct size was
      significantly reduced in the fibrin group (P < .05), and there was a trend toward
      a smaller myocardial infarction in the alginate group. CONCLUSION:
      Intramyocardially injected polymers can be used to reshape the aneurysmal left
      ventricle and might therefore be an approach for myocardial reconstruction and a
      potential option in treating chronic heart failure in human subjects.

PMID- 19154924
TI  - Beating-heart, off-pump mitral valve repair by implantation of artificial chordae
      tendineae: an acute in vivo animal study.
AB  - OBJECTIVE: To evaluate the effectiveness of a new off-pump mitral valve repair
      technology in restoring valve competency in a porcine model of acute mitral
      regurgitation. METHODS: Acute mitral regurgitation was induced in 6 anesthetized
      pigs by cutting anterior leaflet chordae. Artificial chordae were then
      transapically implanted on the prolapsing segment under epicardial
      echocardiographic guidance and secured outside the left ventricular apex. All
      intracardiac manipulations were performed off-pump, through a stab wound incision
      on the left ventricular apex. RESULTS: Cutting the anterior leaflet chordae
      caused an eccentric, posteriorly directed jet of mitral regurgitation that could
      be visualized by color Doppler sonography. Implantation of chordae through the
      left ventricular apex completely eliminated valve regurgitation in 4 animals and
      reduced regurgitation in 2. Intraoperative measurement of artificial chordal
      tensions gave similar values to those reported for native chordae. CONCLUSIONS:
      Off-pump, transapical implantation of artificial chordae between a prolapsing
      anterior mitral valve leaflet and the left ventricular apex was effective in
      reducing acutely induced mitral regurgitation. Long-term studies are planned to
      assess the stability in this animal model.

PMID- 19154925
TI  - Paracorporeal pulsatile biventricular assist device versus extracorporal membrane
      oxygenation-extracorporal life support in adult fulminant myocarditis.
AB  - OBJECTIVE: Biventricular assist device support with a paracorporeal pulsatile
      device is known to be an efficient bridge to recovery for patients with fulminant
      myocarditis-related cardiogenic shock. Whether these patients can be as
      efficiently supported with femorofemoral extracorporeal membrane oxygenation
      remains unclear. METHODS: From 2001 to 2006, 11 patients were referred to our
      cardiac surgery department for fulminant myocarditis-related cardiogenic shock.
      The first 5 patients (mean age, 32 +/- 2 years) were supported with a
      biventricular assist device (Thoratec, Pleasanton, Calif; group I), whereas the
      remaining patients (40 +/- 4 years) were supported with femorofemoral
      extracorporeal membrane oxygenation (group II). Preimplantation probability of
      death was calculated by using the APACHE II score, which was 11 +/- 9 in group I
      versus 24 +/- 18 in group II. RESULTS: One patient in each group died while
      receiving support. In group I the death occurred after 18 days of support in a
      patient who had 45 minutes of external resuscitation before biventricular assist
      device implantation. In group II a patient who remained unstable during
      extracorporeal membrane oxygenation was switched to a biventricular assist device
      13 days later and eventually died of tamponade after 45 days. All other patients
      were weaned from the device after a mean duration of support of 21 +/- 5 days in
      group I versus 13 +/- 4 days in group II. At hospital discharge, the mean
      ejection fraction was 45% +/- 5% in both groups, and at 6 months' follow-up, it
      was 65% and 75%, respectively, in groups I and II. CONCLUSION: In our experience
      extracorporeal membrane oxygenation is as efficient as use of a biventricular
      assist device as a bridge to recovery for patients with fulminant myocarditis
      related cardiogenic shock and facilitates renal and hepatic recovery on support.

PMID- 19154926
TI  - Toward a new cold and warm nondepolarizing, normokalemic arrest paradigm for
      orthotopic heart transplantation.
AB  - OBJECTIVE: Currently, the safe human heart preservation time is limited to around
      4 to 5 hours of cold ischemic storage. Longer arrest times can lead to donor
      heart damage, early graft dysfunction, and chronic rejection. The aim of this
      study was to examine a new nondepolarizing, normokalemic preservation solution
      with adenosine and lidocaine for as long as 6 hours of arrest at cold and warmer
      storage temperatures. METHODS: Isolated perfused rat hearts (n = 87) were
      switched from working to Langendorff (nonworking) mode and arrested at 37 degrees
      C with 200-micromol/L adenosine and 500-micromol/L lidocaine in Krebs-Henseleit
      buffer (10-mmol/L glucose, pH 7.7, 37 degrees C) or with Celsior (Sangstat
      Medical Corp, Fremont, CA). Hearts were removed and placed in static storage at 4
      degrees C for 2 and 6 hours or remained on the apparatus and were intermittently
      flushed at 37 degrees C every 20 minutes for 2 minutes at 68 mm Hg (average
      arrest temperature 28 degrees -30 degrees C) for 2 and 6 hours. We further
      investigated the effect of the warmer adenosine-lidocaine solution supplemented
      with 1- or 5-mmol/L pyruvate. RESULTS: Adenosine-lidocaine solution arrested
      hearts in 16 +/- 2 seconds (n = 32), whereas Celsior did so in 39 +/- 4 seconds
      (n = 23). After 2 hours of cold static storage, there were no functional
      differences between the adenosine-lidocaine and Celsior groups, with
      approximately 70% return of cardiac output. In contrast, after 6 hours of 4
      degrees C storage, adenosine-lidocaine hearts had significantly higher functional
      recoveries (68% +/- 5% cardiac output) than Celsior hearts (47% +/- 14% cardiac
      output) during 60 minutes of reperfusion. In addition, Celsior hearts took 5
      minutes longer to reanimate and showed early reperfusion arrhythmias. At warmer
      temperatures after 2 hours of arrest, adenosine-lidocaine and Celsior hearts were
      not significantly different, despite a 43% higher cardiac output in adenosine
      lidocaine hearts (80% +/- 3% vs 56% +/- 12%). After 6 hours, adenosine-lidocaine
      hearts had recovered 55% +/- 3% of prearrest cardiac output, which increased
      significantly to 75% +/- 4% with addition of 1-mmol/L pyruvate. Adenosine
      lidocaine with 1-mmol/L pyruvate hearts spontaneously recovered 106% heart rate,
      93% to 105% developed pressures, 70% aortic flow, and 81% coronary flow. Coronary
      vascular resistance increased 1.7- to 1.9-fold during the 6-hour arrest. In
      contrast, Celsior hearts did not have return of aortic or coronary flow after 6
      hours in these warmer conditions. CONCLUSION: A new nondepolarizing, normokalemic
      adenosine-lidocaine arrest solution in Krebs-Henseleit buffer with 10-mmol/L
      glucose was versatile at both 4 degrees C and 28 degrees C to 30 degrees C
      relative to Celsior, and the addition of 1-mmol/L pyruvate significantly improved
      cardiac output at warmer arrest temperatures. This new arrest paradigm may be
      useful in the harvest, storage, and implantation of donor hearts.

PMID- 19154927
TI  - Gastrointestinal bleeding rates in recipients of nonpulsatile and pulsatile left
      ventricular assist devices.
AB  - OBJECTIVE: Pulsatile and nonpulsatile left ventricular assist devices are
      effective in managing congestive heart failure. Despite early evidence for
      clinical efficacy, the long-term impact of nonpulsatile flow on end-organ
      function remains to be determined. Our goal was to compare rates of
      gastrointestinal bleeding in nonpulsatile and pulsatile device recipients.
      METHODS: In a retrospective review of 101 left ventricular assist device
      recipients (55 nonpulsatile, 46 pulsatile) from October 31, 2003, to June 1,
      2007, at a single center, gastrointestinal bleeding was defined as guaiac
      positive stool with hemoglobin drop requiring transfusion of at least 2 units of
      packed red blood cells. To assess bleeding risk outside the initial postoperative
      course, any patients with a device in place for 15 days or less was excluded.
      RESULTS: Twelve nonpulsatile and 3 pulsatile left ventricular assist device
      recipients had gastrointestinal bleeding 16 days or longer after device
      implantation. The event rates were 63 events/100 patient-years for nonpulsatile
      devices and 6.8 events/100 patient-years for pulsatile devices (P = .0004). This
      difference persisted for bleeding occurring 31 days or longer after device
      implantation, with 46.5 events/100 patient-years for nonpulsatile devices versus
      4.7 events/100 patient-years for pulsatile devices (P = .0028). Mortalities were
      similar between groups (15% nonpulsatile vs 17% pulsatile, P = .6965).
      CONCLUSION: Patients with nonpulsatile left ventricular assist devices appear to
      have a higher rate of gastrointestinal bleeding events than do pulsatile left
      ventricular assist device recipients. Further prospective evaluation is needed to
      determine potential etiologies and strategies for reducing gastrointestinal
      bleeding in this population.

PMID- 19154928
TI  - Intramyocardial injection of tannic acid attenuates postinfarction remodeling: a
      novel approach to stabilize the breaking extracellular matrix.
AB  - OBJECTIVE: Myocardial infarction is associated with early matrix
      metalloproteinase activation and extracellular matrix degradation. We tested the
      hypothesis that stabilizing the original extracellular matrix of the infarcted
      left ventricle with local injection of tannic acid would preserve cardiac
      structure and function. METHODS: In vitro cytotoxicity of tannic acid was
      performed first; myocardial infarction model was induced by ligation of the left
      anterior descending branch in rats. Tannic acid was intramyocardially injected
      into infarcted site 24 hours after myocardial infarction (n = 30), and saline
      solution was injected in the same way as in the control (n = 30). The matrix
      metalloproteinase activity from tannic acid/saline solution-treated tissues was
      assayed by gelatin zymography 24 hours and 1 week after the treatment. The
      collagen content in the infarcted area was evaluated by hydroxyproline
      colorimetry assay 1 and 4 weeks after the treatment. Left ventricular structure
      and function were also evaluated with echocardiography, hemodynamics, and
      histologic examination. RESULTS: Tannic acid at a concentration of 0.05% had
      minimal cytotoxic effects on cultured cardiomyocytes and thus was subsequently
      chosen as the optimal concentration for injection. Compared with the saline
      solution injection group, tannic acid treatment inhibited the matrix
      metalloproteinase-2/-9 activity and increased the collagen content at the early
      post-myocardial infarction stage (48.6 +/- 7.2 vs 37.3 +/- 6 microg/mg dry
      weight). Tannic acid treatment also significantly reduced infarct expansion
      (infarct expansion index: 1.04 +/- 0.15 vs 1.42 +/- 0.21) and left ventricular
      dilatation at 4 weeks after infarction. Although tannic acid treatment improved
      fractional shortening (26% +/- 2.4% vs 23.3% +/- 3.2%), it failed to alter blood
      pressure (systolic blood pressure: 93.8 +/- 8.2 vs 90.6 +/- 8.5 mm Hg) and rate
      of pressure rise. CONCLUSIONS: Local delivery of tannic acid prevents collagen
      matrix degradation via cross-linking fibrous collagen and inhibiting matrix
      metalloproteinase activity but does not improve the intrinsic contractile
      function of myocardium. This treatment may be helpful to attenuate the adverse
      topographic remodeling after acute myocardial infarction.

PMID- 19154929
TI  - Vagal nerve stimulation prevents reperfusion injury through inhibition of opening
      of mitochondrial permeability transition pore independent of the bradycardiac
      effect.
AB  - BACKGROUND: In spite of recent advances in coronary interventional therapy,
      reperfusion injury is still considered to be a major problem in patients
      undergoing surgical procedures, such as bypass grafting. Here we demonstrate a
      novel therapeutic strategy against ischemia-reperfusion injury: vagally mediated
      prevention of reperfusion-induced opening of mitochondrial permeability
      transition pore. METHODS: We investigated the effects of efferent vagal
      stimulation on myocardial reperfusion injury with ex vivo and in vitro rat
      models. In the ex vivo model the hearts were perfused with intact vagal
      innervation, which allowed us to study the effects of the vagal nerve on the
      heart without other systemic effects. RESULTS: Compared with sham stimulation,
      vagal stimulation exerted a marked anti-infarct effect irrespective of the heart
      rate (34% +/- 6% vs 85% +/- 9% at a heart rate of 300 beats/min, 37% +/- 4% vs
      43% +/- 5% at a heart rate of 250 beats/min, and 39% +/- 4% vs 88% +/- 7% at a
      heart rate of 350 beats/min) after a 30-minute period of global ischemia,
      activated cell-survival Akt cascade, prevented downregulation of the
      antiapoptotic protein Bcl-2, and suppressed cytochrome-c release and caspase-3
      activation. Furthermore, vagal stimulation-treated hearts exhibited a significant
      improvement in left ventricular developed pressure (78 +/- 5 vs 45 +/- 8 mm Hg)
      and a significant attenuation in an incremental change in left ventricular end
      diastolic pressure during reperfusion. These beneficial effects of vagal
      stimulation were abolished by a permeability transition pore opener,
      atractyloside. In the in vitro study with primary-cultured cardiomyocytes,
      acetylcholine prevented a reoxygenation-induced collapse in mitochondrial
      transmembrane potential through inhibition of permeability transition pore
      opening. CONCLUSION: Vagal stimulation would be a potential adjuvant therapy for
      the rescue of ischemic myocardium from reperfusion injury, and the protective
      effects are independent of its bradycardiac effects.

PMID- 19154930
TI  - Regression of pressure-induced left ventricular hypertrophy is characterized by a
      distinct gene expression profile.
AB  - OBJECTIVE: Left ventricular hypertrophy is a highly prevalent and robust
      predictor of cardiovascular morbidity and mortality. Existing studies have finely
      detailed mechanisms involved with its development, yet clinical translation of
      these findings remains unsatisfactory. We propose an alternative strategy
      focusing on mechanisms of left ventricular hypertrophy regression rather than its
      progression and hypothesize that left ventricular hypertrophy regression is
      associated with a distinct genomic profile. METHODS: Minimally invasive
      transverse arch banding and debanding (or their respective sham procedures) were
      performed in C57Bl6 male mice. Left ventricular hypertrophy was assessed
      physiologically by means of transthoracic echocardiographic analysis,
      structurally by means of histology, and molecularly by means of real-time
      polymerase chain reaction. Mouse hearts were genomically analyzed with Agilent
      (Santa Clara, Calif) mouse 44k developmental gene chips. RESULTS: Compared with
      control animals, animals banded for 28 days had a robust hypertrophic response,
      as determined by means of heart weight/body weight ratio, histologic analysis,
      echocardiographic analysis, and fetal gene expression. These parameters were
      reversed within 1 week of debanding. Whole-genome arrays on left ventricular
      tissue revealed 288 genes differentially expressed during progression, 265 genes
      differentially expressed with regression, and only 23 genes shared by both
      processes. Signaling-related expression patterns were more prevalent with
      regression rather than the structure-related patterns associated with left
      ventricular hypertrophy progression. In addition, regressed hearts showed
      comparatively more changes in energy metabolism and protein production.
      CONCLUSIONS: This study demonstrates an effective model for characterizing left
      ventricular hypertrophy and reveals that regression is genomically distinct from
      its development. Further examination of these expression profiles will broaden
      our understanding of left ventricular hypertrophy and provide a novel therapeutic
      paradigm focused on promoting regression of left ventricular hypertrophy and not
      just halting its progression.

PMID- 19154931
TI  - An unusual case of nonbacterial thrombotic (marantic) endocarditis.

PMID- 19154932
TI  - Compressed true lumen in the innominate artery: a pitfall of right axillary
      arterial perfusion in acute aortic dissection.

PMID- 19154933
TI  - Partial left ventricular support implanted through minimal access surgery as a
      bridge to cardiac transplant.

PMID- 19154934
TI  - A bilobed thoracic outlet mass: options for resection.

PMID- 19154935
TI  - Repair of acute postinfarction atrioventricular dehiscence in a patient with
      posterior left ventricular aneurysm.

PMID- 19154936
TI  - Video-assisted thoracoscopic bullectomy for an infectious giant bulla with the
      concomitant use of the perioperative intracavity fluid suction.

PMID- 19154937
TI  - Incomplete transmural ablation caused by bipolar radiofrequency ablation devices.

PMID- 19154939
TI  - En bloc esophagectomy reduces local recurrence and improves survival compared
      with transhiatal resection after neoadjuvant therapy for esophageal
      adenocarcinoma.

PMID- 19154940
TI  - Remediastinoscopy: a statistical reinterpretation.

PMID- 19154942
TI  - Referent values and equipoise: editors' notes.

PMID- 19154943
TI  - Spironolactone alleviates late cardiac remodeling after left ventricular
      restoration.

PMID- 19154945
TI  - Glimepiride increases high-density lipoprotein cholesterol via increasing
      adiponectin levels in type 2 diabetes mellitus.
AB  - The aims of the present study are to investigate the effect of glimepiride 1 mg/d
      on plasma adiponectin and to assess the contribution of adiponectin in changing
      high-density lipoprotein cholesterol (HDL-c) levels after glimepiride treatment.
      Forty patients with type 2 diabetes mellitus were included. Plasma adiponectin,
      fasting plasma glucose, insulin, hemoglobin A(1c), and cholesterol were measured
      at study entry and after 3 months of treatment with glimepiride. Both plasma
      adiponectin level (7.5 +/- 4.5 vs 8.3 +/- 4.5 microg/mL, P = .040) and HDL-c
      level increased significantly (50 +/- 11 vs 53 +/- 10 mg/dL, P = .041) in the all
      subjects group. In the low-adiponectin group (initial plasma adiponectin level <6
      microg/mL), both plasma adiponectin level (4.5 +/- 0.9 vs 5.9 +/- 2.0 microg/mL,
      P = .004) and HDL-c level increased significantly (44 +/- 8 vs 49 +/- 9 mg/dL, P
      = .011). There was no significant change in the high-adiponectin group (initial
      plasma adiponectin level >or=6 microg/mL). Change in plasma adiponectin level was
      an independent factor for change in HDL-c level after adjustment for other
      factors (beta = .574, P = .009, R(2) = 0.524, P = .036). In conclusion,
      glimepiride improved plasma adiponectin level, especially in the subjects with
      type 2 diabetes mellitus with low adiponectin level before treatment, and may
      directly contribute to improving HDL-c level.

PMID- 19154946
TI  - The atypical presentation of the metabolic syndrome components in black African
      women: the relationship with insulin resistance and the influence of regional
      adipose tissue distribution.
AB  - The appropriateness of the metabolic syndrome criteria as an indicator of
      cardiovascular disease risk has been challenged in black Africans. Hence, the
      aims of this study were (1) to examine the level of agreement between the
      International Diabetes Federation (IDF) and the National Cholesterol Education
      Program Adult Treatment Panel III (ATP III) metabolic syndrome criteria, which
      differ in their emphasis on central obesity; (2) to investigate the degree to
      which these criteria predict insulin resistance, as estimated by the homeostasis
      model assessment of insulin resistance (HOMA-IR); and (3) to investigate the
      extent to which a diagnosis of the metabolic syndrome and insulin resistance may
      be explained by body fat and its distribution. In 103 normal-weight (body mass
      index <or=25 kg/m(2), mean: 22.0 +/- 1.8 kg/m(2)) and 119 obese (body mass index
      >or=30 kg/m(2), mean: 33.9 +/- 5.5 kg/m(2)) urbanized black South African women
      (27 +/- 7 years old), body composition (dual-energy x-ray absorptiometry), fat
      distribution (waist and computed tomography), blood pressure, fasting glucose,
      HOMA-IR, and lipid profiles were measured. Insulin resistance was defined as the
      upper tertile of HOMA-IR. The overall proportion of individuals who met the IDF
      and ATP III metabolic syndrome criteria were 13% and 10%, respectively. Agreement
      was high between the IDF and ATP III metabolic syndrome criteria (kappa = 0.87);
      however, neither criteria predicted HOMA-IR (kappa = 0.16, 95% confidence
      interval: 0.05-0.27 and 0.14, 95% confidence interval: 0.05-0.27, respectively).
      Visceral adipose tissue was the largest contributor to diagnosis of the metabolic
      syndrome, and waist alone (>80 cm or >88 cm) had an improved specificity (21% or
      18% higher, respectively) and positive predictive value (64% or 57% higher,
      respectively) for identifying insulin resistance compared with the metabolic
      syndrome criteria. Waist circumference was a better predictor of HOMA-IR than the
      IDF or ATP III metabolic syndrome criteria in young black African women without
      known disease. The measurement of waist circumference, as an indicator of disease
      risk, should therefore be encouraged in the public health setting.

PMID- 19154947
TI  - The association of desaturase 9 and plasma fatty acid composition with insulin
      resistance-associated factors in female adolescents.
AB  - Desaturase 9 (Delta 9), which converts saturated fatty acids (SFAs) into
      monounsaturated fatty acids, is an important component in leptin-mediated energy
      homeostasis in rodent models. Few human studies, however, have been performed
      regarding the clinical relevance of Delta 9, particularly whether Delta 9 is
      involved in the relationship between blood fatty acid profiles and insulin
      resistance-associated factors. The aim of the present study was to examine fatty
      acid data from 178 apparently healthy female adolescents and determine whether
      (a) Delta 9 has independent associations with adiposity, insulin resistance
      level, and fasting plasma polyunsaturated fatty acids (PUFAs); (b) Delta 9 is a
      predictor of fasting blood lipid profile; and (c) the associations between
      fasting plasma fatty acid component and insulin resistance level are independent
      of abdominal obesity level. Desaturase 9-16 (surrogate of Delta 9 as calculated
      by plasma ratio C16:1 n-7/C16:0) correlated with waist girth (r = .160, P < .05),
      homeostasis model assessment of insulin resistance (HOMA-IR) (r = .201, P < .01),
      plasma PUFAs (eg, C20:4 n-6 [r = -.269, P < .001], C22:6 n-3 [r = -.274, P <
      .001]). After adjustment for dietary SFAs, Delta 9-16 had stronger correlation
      with waist (r = .227, P < .01) and significant correlation with PUFAs, whereas it
      had a nonsignificant correlation with HOMA-IR. The same pattern was observed with
      Delta 9-18 (surrogate of Delta 9 as calculated by plasma ratio C18:1 n-9/C18:0).
      After adjustment for dietary SFAs, waist, and HOMA-IR, Delta 9-16 and Delta 9-18
      were still positive predictors of triglyceride (both P < .001) and apolipoprotein
      B (Delta 9-18, P < .001; Delta 9-16, P = .052). After adjustment for waist, HOMA
      IR only remained a positive determinant of medium-chain SFAs (C14:0, P < .001;
      C16:0, P < .05); but it emerged to be inversely related to C20:4 n-6 (P < 0.1).
      The positive and independent associations of medium-chain SFAs with insulin
      resistance level suggest their vital roles in diabetes pathogenesis, whereas
      certain PUFAs such as C20:4 n-6 appear to be protective. The observed
      associations of Delta 9 with adiposity and plasma lipid profile in these
      apparently healthy female adolescents support the concept derived from rodent
      models that Delta 9 activity is independently reflective of higher body mass
      index and higher circulatory triglyceride levels.

PMID- 19154948
TI  - Hepatocyte growth factor levels are associated with the results of 123I
      metaiodobenzylguanidine myocardial scintigraphy in patients with type 2 diabetes
      mellitus.
AB  - Elevated hepatocyte growth factor (HGF) levels and cardiovascular autonomic
      dysfunction are associated with a high mortality rate in patients with type 2
      diabetes mellitus. We tested the hypothesis that elevated HGF is associated with
      insulin resistance and cardiovascular autonomic dysfunction in patients with type
      2 diabetes mellitus not receiving insulin treatment. The study group consisted of
      21 type 2 diabetes mellitus patients with high HGF levels (>0.26 ng/mL, 58 +/- 5
      years old, high-HGF group). The control group consisted of 25 type 2 diabetes
      mellitus patients with normal HGF levels (<or=0.26 ng/mL, 58 +/- 9 years old,
      normal-HGF group). Cardiovascular autonomic function was assessed by baroreflex
      sensitivity, heart rate variability, plasma norepinephrine concentrations, and
      cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphy. Early and delayed
      (123)I-MIBG myocardial uptake values were lower (P < .005 and P < .01,
      respectively) and the percentage of washout rate of (123)I-MIBG was higher (P <
      .001) in the high-HGF group than in the normal-HGF group. The fasting plasma
      insulin concentrations (P < .0001) and the homeostasis model assessment index
      values (P < .0001) were higher in the high-HGF group than in the normal-HGF
      group. Multiple regression analysis revealed that the level of HGF was
      independently predicted by the homeostasis model assessment index values and the
      myocardial uptake of (123)I-MIBG at the delayed phase. Our results demonstrate
      that high levels of HGF are associated with depressed cardiovascular autonomic
      function and insulin resistance in patients with type 2 diabetes mellitus.

PMID- 19154949
TI  - Fasting plasma total ghrelin concentrations in monozygotic twins discordant for
      obesity.
AB  - Ghrelin is a hormone that is involved in the regulation of food intake. Neuronal,
      endocrine, and genetic factors have been shown to regulate plasma ghrelin levels;
      but the determinants of fasting ghrelin concentrations are not yet fully
      understood. The main aim was to explore the roles of adiposity and genetic
      differences in determining fasting plasma total ghrelin levels. We measured total
      ghrelin levels in a population of 23 monozygotic twin pairs discordant for
      obesity. In addition, 2 variants of ghrelin gene, namely, Arg51Gln and Leu72Met,
      were genotyped in 3 populations of monozygotic twin pairs: 23 obesity-discordant,
      43 lean-concordant, and 46 obesity-concordant twin pairs. In discordant twins,
      lean co-twins had higher fasting plasma total ghrelin levels (950 pg/mL, SD = 328
      pg/mL) than obese twins (720 pg/mL, SD = 143 pg/mL; P = .003). Arg51Gln
      polymorphism of the ghrelin gene was equally distributed between the twin groups.
      However, there were significant differences in genotype frequencies at the
      Leu72Met polymorphism between the discordant and obese-concordant groups (P =
      .003) and between the discordant and lean-concordant groups (P = .011), but not
      between the 2 concordant groups. In the discordant group, there were fewer Met
      carriers (4%) than among the obese (17%) or the lean-concordant groups (15%).
      Plasma total ghrelin levels are affected by acquired obesity independent of
      genetic background. The Leu72 allele is particularly common among monozygotic
      twins discordant for obesity, suggesting that this ghrelin allele is more
      permissive in the regulation of energy balance. The ghrelin gene may thus play a
      role in the regulation of variability of body weight, such that Leu72 allele
      carriers are more prone to weight variability in response to environmental
      factors.

PMID- 19154950
TI  - Associations between circulating free fatty acids, visceral adipose tissue
      accumulation, and insulin sensitivity in postmenopausal women.
AB  - The aims of the study were to evaluate the contribution of visceral adipose
      tissue (AT) accumulation and insulin sensitivity to the determination of
      circulating free fatty acid (FFA) concentrations measured during a 2-hour
      euglycemic-hyperinsulinemic clamp and to verify whether elevated FFAs are
      associated with other components of the metabolic syndrome in postmenopausal
      women. This cross-sectional study included 115 postmenopausal women (46-68 years
      old). Visceral AT was estimated by computed tomography. Insulin sensitivity was
      assessed by a 2-hour euglycemic-hyperinsulinemic clamp. Free fatty acid
      concentration was measured in the fasting state and every 30 minutes during the
      clamp. Fasting plasma glucose and 2-hour plasma glucose were measured by an oral
      glucose tolerance test. Visceral AT was associated positively and insulin
      sensitivity negatively with FFA area under the curve (AUC) measured during the
      clamp. Women with high visceral AT accumulation and low insulin sensitivity had
      higher FFA AUC than women with high visceral AT accumulation and high insulin
      sensitivity or women with low visceral AT combined with either low or high
      insulin sensitivity. Free fatty acid AUC was positively associated with
      triglyceride (r = 0.25, P < .05), fasting plasma glucose (r = 0.26, P < .01), 2
      hour plasma glucose (r = 0.27, P < .01), and diastolic blood pressure (r = 0.21,
      P < .05) independently of visceral AT and insulin sensitivity. In postmenopausal
      women, the presence of both high visceral AT and low insulin sensitivity is
      needed to observe an elevated FFA AUC. Moreover, FFA AUC is associated with some
      components of the metabolic syndrome, independently of visceral AT and insulin
      sensitivity.

PMID- 19154952
TI  - Hepatic fat is not associated with beta-cell function or postprandial free fatty
      acid response.
AB  - We evaluated the association of hepatic fat with beta-cell function estimated
      from the oral glucose tolerance test. In addition, we tested the hypothesis that
      postprandial free fatty acid (FFA) suppression after a meal tolerance test (MTT)
      is linked to hepatic fat. Individuals with normal glucose metabolism (NGM; n = 10
      with low and n = 10 with high insulin secretion, matched for insulin sensitivity
      and sex), impaired glucose metabolism (IGM; n = 14), and type 2 diabetes mellitus
      (DM; n = 14) underwent a 75-g oral glucose tolerance test and MTT. beta-Cell
      function estimates were calculated from C-peptide using a mathematical model.
      Liver fat was quantified by proton magnetic resonance ((1)H-MR) spectroscopy.
      Area under the curve (AUC) of triglycerides (TG) and FFA responses during MTT
      represented postprandial lipid responses. Linear regression models were adjusted
      for age, sex, and additionally for insulin sensitivity for IGM/DM subjects. Liver
      fat content was equal for the NGM groups with low and high insulin secretion:
      4.5% (2.6-6.0) (median, interquartile range) and 4.9% (2.3-7.8), respectively;
      liver fat percentages of IGM and diabetic subjects were significantly higher:
      11.2 (6.7-21.1) and 10.0 (7.8-24.5). Liver fat showed a fairly strong,
      significant negative association with insulin sensitivity, but was not associated
      with beta-cell function. Significant associations of liver fat with fasting TG
      and AUC(TG) were shown in the total study population and in IGM/DM subjects
      separately. No relationship existed between fasting FFA or AUC(FFA) and liver
      fat. We conclude that fat accumulation in the liver is tightly linked to insulin
      sensitivity but not to beta-cell function. Furthermore, liver fat is associated
      with circulating TG levels, but not with FFA concentrations.

PMID- 19154953
TI  - The expression of rat resistin isoforms is differentially regulated in visceral
      adipose tissues: effects of aging and food restriction.
AB  - Two variants of the adipose hormone resistin are generated by alternative
      splicing in Wistar rats. Here we analyzed the expression of these resistin
      variants in 2 main visceral adipose depots, epididymal and retroperitoneal, as
      well as the resistin serum concentration during aging and food restriction. Total
      protein levels of resistin were also analyzed in extracts from both visceral
      adipose depots. Resistin variants show similar patterns of relative expression in
      visceral adipose tissues in 3-month-old rats, representing the short variant, s
      resistin, which is 15% of the full-length transcript. However, only epididymal,
      but not retroperitoneal, fat pad shows a decrease in both messenger RNA and
      protein levels of resistin isoforms with aging. Food restriction decreases
      adiposity index in 8- and 24-month-old animals to values even lower than those of
      3-month-old animals. Food restriction decreases resistin expression in both
      adipose tissues in 8-month-old but not in 24-month-old rats. Interestingly,
      concomitant with the improvement of insulin sensitivity asserted by homeostasis
      model assessment, resistin serum levels decrease only in food-restricted 8-month
      old animals. In contrast, food restriction up-regulates s-resistin messenger RNA
      in epididymal adipose tissue, whereas no significant changes are appreciated in
      retroperitoneal adipose tissue. These data indicate that both forms of resistin
      are differentially regulated by fat depot location, aging, and even nutritional
      status, suggesting that alternative splicing plays a key role in this
      differential regulation.

PMID- 19154951
TI  - Differential influence of different dietary fatty acids on very low-density
      lipoprotein secretion when delivered to hepatocytes in chylomicron remnants.
AB  - The influence of dietary fats carried in chylomicron remnants on the hepatic
      secretion of very low-density lipoprotein (VLDL) was investigated using
      chylomicron remnant-like particles (CRLPs) and cultured rat hepatocytes as the
      experimental model. Chylomicron remnant-like particles containing triacylglycerol
      (TG) from palm, olive, or corn (enriched in saturated, monounsaturated, or n-6
      polyunsaturated fatty acids) oil, respectively, were incubated with cultured
      hepatocytes for 5 hours. The medium was then removed and replaced with medium
      without CRLPs; and the secretion of TG, cholesterol, and apolipoprotein B48
      during the following 16 hours was determined. Secretion of TG into the d less
      than 1.050-g/mL fraction containing VLDL was unaffected by olive CRLPs, but was
      significantly increased in cells exposed to palm or corn CRLPs in comparison with
      both olive CRLPs and control incubations without CRLPs. Secretion of
      apolipoprotein B48, however, was not changed by any of the CRLP types.
      Apolipoprotein B messenger RNA levels were decreased by olive and corn CRLPs, and
      3-hydroxy-3-methylglutaryl coenzyme A reductase messenger RNA abundance was
      increased by palm CRLPs; but expression of other genes involved in the regulation
      of VLDL secretion was unaffected. These findings demonstrate that CRLPs enriched
      in saturated fatty acids or n-6 polyunsaturated fatty acids increase the
      secretion of TG in VLDL, possibly because of the secretion of larger particles,
      whereas those enriched in monounsaturated fatty acids have no effect. Thus,
      different dietary fats have differential effects on VLDL secretion directly when
      delivered to the liver in chylomicron remnants.

PMID- 19154955
TI  - Validity of the reduced-sample insulin modified frequently-sampled intravenous
      glucose tolerance test using the nonlinear regression approach.
AB  - The disposition index, the product of the insulin sensitivity index (S(I)) and
      the acute insulin response to glucose, is linked in African Americans to
      chromosome 11q. This link was determined with S(I) calculated with the nonlinear
      regression approach to the minimal model and data from the reduced-sample insulin
      modified frequently-sampled intravenous glucose tolerance test (Reduced-Sample-IM
      FSIGT). However, the application of the nonlinear regression approach to
      calculate S(I) using data from the Reduced-Sample-IM-FSIGT has been challenged as
      being not only inaccurate but also having a high failure rate in insulin
      resistant subjects. Our goal was to determine the accuracy and failure rate of
      the Reduced-Sample-IM-FSIGT using the nonlinear regression approach to the
      minimal model. With S(I) from the Full-Sample-IM-FSIGT considered the standard
      and using the nonlinear regression approach to the minimal model, we compared the
      agreement between S(I) from the Full- and Reduced-Sample-IM-FSIGT protocols. One
      hundred African Americans (body mass index, 31.3 +/- 7.6 kg/m(2) [mean +/- SD];
      range, 19.0-56.9 kg/m(2)) had FSIGTs. Glucose (0.3 g/kg) was given at baseline.
      Insulin was infused from 20 to 25 minutes (total insulin dose, 0.02 U/kg). For
      the Full-Sample-IM-FSIGT, S(I) was calculated based on the glucose and insulin
      samples taken at -1, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 14, 16, 19, 22, 23, 24, 25,
      27, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180 minutes. For the Reduced
      Sample-FSIGT, S(I) was calculated based on the time points that appear in bold.
      Agreement was determined by Spearman correlation, concordance, and the Bland
      Altman method. In addition, for both protocols, the population was divided into
      tertiles of S(I). Insulin resistance was defined by the lowest tertile of S(I)
      from the Full-Sample-IM-FSIGT. The distribution of subjects across tertiles was
      compared by rank order and kappa statistic. We found that the rate of failure of
      resolution of S(I) by the Reduced-Sample-IM-FSIGT was 3% (3/100). For the
      remaining 97 subjects, S(I) for the Full- and Reduced-Sample-IM-FSIGTs were as
      follows: 3.76 +/- 2.41 L mU(-1) min(-1) (range, 0.58-14.50) and 4.29 +/- 2.89 L
      mU(-1) min(-1) (range, 0.52-14.42); relative error, 21% +/- 18%; Spearman r =
      0.97; and concordance, 0.94 (both P < .001). After log transformation, the Bland
      Altman limits of agreement were -0.29 and 0.53. The exact agreement for
      distribution of the population in the insulin-resistant tertile vs the insulin
      sensitive tertiles was 92%, kappa of 0.82 +/- 0.06. Using the nonlinear
      regression approach and data from the Reduced-Sample-IM-FSIGT in subjects with a
      wide range of insulin sensitivity, failure to resolve S(I) occurred in only 3% of
      subjects. The agreement and maintenance of rank order of S(I) between protocols
      support the use of the nonlinear regression approach to the minimal model and the
      Reduced-Sample-IM-FSIGT in clinical studies.

PMID- 19154954
TI  - Combined hyperlipidemia in relation to race/ethnicity, obesity, and insulin
      resistance in the Multi-Ethnic Study of Atherosclerosis.
AB  - We have asked whether the prevalence of combined hyperlipidemia (CHL) differs by
      race/ethnicity, obesity, and insulin resistance in a contemporary, multiethnic,
      US cohort. We determined the prevalence and adjusted odds of CHL in a cohort of
      5923 men and women free of clinically recognized cardiovascular disease and
      diabetes according to race/ethnicity (white, Chinese, African American, and
      Hispanic), obesity, and insulin resistance. Untreated lipid values were imputed
      for those on lipid-lowering therapy. Combined hyperlipidemia was defined using
      age- and sex-specific greater than or equal to 75th percentile cut points for low
      density lipoprotein cholesterol and triglycerides obtained from a predominantly
      white North American population study. Compared with whites, adjusted odds ratios
      for CHL were 0.48 in African Americans (95% confidence interval [CI], 0.30-0.75),
      1.33 in Hispanics (95% CI, 0.93-1.91), and 1.06 in Asians (95% CI, 0.62-1.82).
      Within the entire population, the adjusted odds of CHL were over 2-fold higher in
      overweight and obese participants compared with normal-weight participants and
      more than 4-fold higher in quartiles 2 through 4 of insulin resistance compared
      with quartile 1. African Americans had lower odds for CHL than whites despite
      higher body mass index and abdominal adiposity. Hispanics had a nonsignificantly
      higher trend, and Asians had no significantly different odds than whites. Modest
      increases in weight and insulin resistance were associated with significantly
      higher odds of CHL in a multiethnic US population. Further research is needed to
      determine the most efficacious diet, exercise, and drug management to decrease
      the risk of CHL and coronary heart disease among racial/ethnic groups in the
      United States.

PMID- 19154956
TI  - Peroxisome proliferator-activated receptor alpha and enzymes of carnitine
      biosynthesis in the liver are down-regulated during lactation in rats.
AB  - This study investigated the hypothesis that lactation lowers gene expression of
      peroxisome proliferator-activated receptor (PPAR) alpha in the liver and that
      this leads to a down-regulation of hepatic enzymes involved in carnitine
      synthesis and novel organic cation transporters (OCTNs). Thirty-two pregnant
      female rats were divided into 4 groups. In the first group, all pups were
      removed, whereas in the other groups, litters were adjusted to sizes of 4, 10, or
      18 pups per dam. Dams suckling their litters, irrespective of litter size, had
      lower relative messenger RNA concentrations of PPARalpha, various classic
      PPARalpha target genes involved in fatty acid catabolism, as well as enzymes
      involved in carnitine synthesis (trimethyllysine dioxygenase, 4-N
      trimethylaminobutyraldehyde dehydrogenase, gamma-butyrobetaine dioxygenase) and
      OCTN1 in the liver than dams whose litters were removed (P < .05). Moreover, dams
      suckling their litters had a reduced activity of gamma-butyrobetaine dioxygenase
      in the liver and reduced concentrations of carnitine in plasma, liver, and muscle
      compared with dams without litters (P < .05). In conclusion, the present study
      demonstrates for the first time that lactation leads to a down-regulation of
      PPARalpha and genes involved in hepatic carnitine synthesis and uptake of
      carnitine (OCTN1) in the liver, irrespective of litter size. It is moreover
      suggested that down-regulation of PPARalpha in the liver may be a means to
      conserve energy and metabolic substrates for milk production in the mammary
      gland.

PMID- 19154957
TI  - Should high creatine kinase discourage the initiation or continuance of statins
      for the treatment of hypercholesterolemia?
AB  - Patients with high low-density lipoprotein cholesterol (LDLC) and asymptomatic
      high creatine kinase (CK) (>or=250 but <2500 IU/L, 10x the laboratory upper
      normal limit [UNL]) are often not started on statins or have statins stopped
      because of concern about myositis-rhabdomyolysis. In the current report, we
      prospectively examined the hypothesis that asymptomatic patients with high CK
      (>or=250 but <2500 IU/L) tolerate statins well at doses reducing LDLC to target,
      less than 100 mg/dL, without development of myalgia-myositis. We assessed
      outcomes of 3 groups of patients referred to us because of asymptomatic high CK
      (>or=250 but <2500 IU/L)--1 group (n = 29) on statins at referral and continued
      on statins, 1 group (n = 20) not on statins and started on statins, and 1 group
      (n = 19) not on statins and not given statins--all restudied 1 month after entry
      and then every 3 months. Of the 68 patients, 59 (87%) had CK greater than 1 to 3
      times the UNL, 7 (10%) had CK greater than 3 to 5 times the UNL, and 2 (3%) had
      CK greater than 5 to 10 times the UNL. After 1.2 months of follow-up in 29 statin
      ->statin patients, median CK fell from 353 to 301 (P = .0018) and was 287 (P =
      .015) after 4 months. After 1.3 months of follow-up in 20 no statin-->statin
      patients, median CK fell from 397 to 292 (P = .0094) and was 419 after 4.1
      months. After 1.1 months of follow-up in 19 no statin-->no statin patients,
      median CK fell from 392 to 323 (P = .14) and was 271 (P = .029) after 4.2 months.
      By repeated-measures analysis, there were no differences in entry CK among the 3
      treatment groups; CK fell (P = .04) in the no statin-->no statin patients.
      Despite high baseline CK (48 patients with CK 1-5x the UNL, 1 with CK 5-10x UNL),
      no patients during follow-up on statins developed CK greater than 10 times the
      UNL (2500 IU/L), none discontinued statins or reduced statin dose because of
      myalgia-myositis, and there was no rhabdomyolysis. High pretreatment CK,
      particularly 1 to 5 times the UNL, should not be an impediment to start or
      continue statins to lower LDLC.

PMID- 19154958
TI  - Adiponectin isoform distribution in women--relationship to female sex steroids
      and insulin sensitivity.
AB  - Little is known about the associations between adiponectin and its oligomeric
      isoforms with female sex steroids, and the relevance of these relationships to
      insulin sensitivity in women. In a cross-sectional study of 32 healthy women (12
      premenopausal, 10 postmenopausal, and 10 early pregnant), we investigated the
      correlations of total adiponectin and the high-, medium-, and low-molecular
      weight oligomers (HMW, MMW, and LMW, respectively) with estrogen, progesterone,
      adiposity, and insulin resistance. Fat mass and serum concentrations of
      estradiol, progesterone, insulin, glucose, and total and isoform adiponectin were
      measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was
      calculated. Serum concentrations of total and HMW adiponectin were highest in
      postmenopausal women and lowest in pregnant women. Concentrations of the MMW and
      LMW isoforms were not significantly different between the 3 groups. Total
      adiponectin, HMW adiponectin, and MMW adiponectin were negatively associated with
      estradiol and progesterone; but no associations between the LMW isoform and
      female sex steroids were observed. Fat mass and HOMA-IR were highest in pregnant
      women and lowest in premenopausal women. The HOMA-IR was positively associated
      with fat mass, estradiol, and progesterone, and negatively associated with total,
      HMW, and MMW adiponectin. Multivariate stepwise regression analysis revealed that
      fat mass explained 34% of the variance in HOMA-IR and that total and isoform
      adiponectin contributed an additional 10% to 15%. In the multivariate linear
      regression analysis, there were significant interactions of estradiol and
      progesterone with adiponectin or fat mass in the associations with HOMA-IR. In
      conclusion, there are strong negative associations of serum adiponectin and some
      of its isoforms with estradiol and progesterone. Female sex steroids are likely
      to affect insulin sensitivity through modulation of adiponectin and body fat.

PMID- 19154959
TI  - Effect of acute high-intensity intermittent swimming on post-exercise insulin
      responsiveness in epitrochlearis muscle of fed rats.
AB  - Maximally insulin-stimulated glucose uptake in skeletal muscle, ie, insulin
      responsiveness, is reduced in fed animals as compared with fasted animals; but
      acute prior endurance exercise improves insulin responsiveness in the muscles of
      fed rats. The effect of acute prior sprint interval exercise on insulin
      responsiveness in the muscles of fed animals has not been clarified, and we
      therefore compared the effect of short high-intensity swimming as a model of
      sprint interval exercise on insulin responsiveness in the muscles of fed rats
      with the effect of prolonged low-intensity swimming as a model of endurance
      exercise. The fed rats were subjected to an acute bout of high-intensity
      intermittent swimming (HIS) or low-intensity continuous swimming (LIS). The HIS
      rats swam for eight 20-second periods with a weight equal to 18% of their body
      weight. The LIS rats swam with no load for 3 hours. HIS increased (P < .05) the
      phosphorylation of adenosine monophosphate-activated protein kinase (AMPK)
      Thr(172) and that of its downstream target acetyl-CoA carboxylase (ACC) Ser(79)
      12.6- and 3.1-fold, respectively, whereas LIS increased them 3.8- and 1.9-fold,
      respectively, immediately after exercise compared with rested muscle. HIS and LIS
      increased the insulin responsiveness of 2-deoxyglucose uptake measured 4 hours
      after exercise by 39% and 41%, respectively, compared with rested muscles. These
      results show that very short (160 seconds) HIS exercise with greater AMPK
      activation increases the responsiveness of glucose uptake to insulin in the
      muscles of fed rats to a similar level observed after prolonged (3 hours) LIS
      exercise with lower AMPK activation. Therefore, it is suggested that an acute
      bout of sprint interval exercise that activates AMPK to a sufficiently high level
      can increase post-exercise insulin responsiveness on muscle glucose uptake
      irrespective of very short exercise duration.

PMID- 19154960
TI  - Effects of antioxidant supplementation on insulin sensitivity, endothelial
      adhesion molecules, and oxidative stress in normal-weight and overweight young
      adults.
AB  - The objective of the study was to determine whether short-term antioxidant (AOX)
      supplementation affects insulin sensitivity, endothelial adhesion molecule
      levels, and oxidative stress in overweight young adults. A randomized, double
      blind, controlled study tested the effects of AOXs on measures of insulin
      sensitivity (homeostasis model assessment [HOMA]) and quantitative insulin
      sensitivity check index), endothelial adhesion molecules (soluble intercellular
      adhesion molecule-1, vascular adhesion molecule, and endothelial-leukocyte
      adhesion molecule-1), adiponectin, and oxidative stress (lipid hydroperoxides) in
      overweight and normal-weight individuals (N = 48, 18-30 years). Participants
      received either AOX (vitamin E, 800 IU; vitamin C, 500 mg; beta-carotene, 10 mg)
      or placebo for 8 weeks. The HOMA values were initially higher in the overweight
      subjects and were lowered with AOX by week 8 (15% reduction, P = .02).
      Adiponectin increased in both AOX groups. Soluble intercellular adhesion molecule
      1 and endothelial-leukocyte adhesion molecule-1 decreased in overweight AOX
      treated groups by 6% and 13%, respectively (P < .05). Plasma lipid hydroperoxides
      were reduced by 0.31 and 0.70 nmol/mL in the normal-weight and overweight AOX
      treated groups, respectively, by week 8 (P < .05). Antioxidant supplementation
      moderately lowers HOMA and endothelial adhesion molecule levels in overweight
      young adults. A potential mechanism to explain this finding is the reduction in
      oxidative stress by AOX. Long-term studies are needed to determine whether AOXs
      are effective in suppressing diabetes or vascular activation over time.

PMID- 19154961
TI  - Oxalic acid excretion after intravenous ascorbic acid administration.
AB  - Ascorbic acid is frequently administered intravenously by alternative health
      practitioners and, occasionally, by mainstream physicians. Intravenous
      administration can greatly increase the amount of ascorbic acid that reaches the
      circulation, potentially increasing the risk of oxalate crystallization in the
      urinary space. To investigate this possibility, we developed gas chromatography
      mass spectrometry methodology and sampling and storage procedures for oxalic acid
      analysis without interference from ascorbic acid and measured urinary oxalic acid
      excretion in people administered intravenous ascorbic acid in doses ranging from
      0.2 to 1.5 g/kg body weight. In vitro oxidation of ascorbic acid to oxalic acid
      did not occur when urine samples were brought immediately to pH less than 2 and
      stored at -30 degrees C within 6 hours. Even very high ascorbic acid
      concentrations did not interfere with the analysis when oxalic acid extraction
      was carried out at pH 1. As measured during and over the 6 hours after ascorbic
      acid infusions, urinary oxalic acid excretion increased with increasing doses,
      reaching approximately 80 mg at a dose of approximately 100 g. We conclude that,
      when studied using correct procedures for sample handling, storage, and analysis,
      less than 0.5% of a very large intravenous dose of ascorbic acid is recovered as
      urinary oxalic acid in people with normal renal function.

PMID- 19154962
TI  - Adipogenic risk factor differences between Korean and white adults--potential
      role of plasma free fatty acid and adiponectin.
AB  - Asian adults are at greater risk for metabolic abnormalities (insulin resistance,
      dyslipidemia) at the same body mass index (BMI) than are whites. Elevated free
      fatty acids (FFA) and decreased adiponectin are linked with these same metabolic
      abnormalities. We tested the hypothesis that fasting plasma FFA are greater and
      adiponectin concentrations are lower in Korean than white adults matched for age,
      sex, and BMI. Plasma FFA and adiponectin concentrations were analyzed using a
      microfluorometric assay and radioimmunoassay, respectively. Fasting plasma FFA
      concentrations were not different (P = .51) between Korean and white subjects
      (208 [183-232] vs 215 [168-262] mumol/L, median and 95% confidence interval).
      Despite similar body composition in the 2 groups, the plasma adiponectin
      concentrations in Koreans were significantly lower than those in whites in men,
      women, and total subgroups (adjusted mean +/- SEM: 4.9 +/- 0.8 vs 9.1 +/- 0.8
      microg/mL, P = .004; 8.9 +/- 1.0 vs 13.2 +/- 1.0 microg/mL, P = .006; and 6.5 +/-
      0.6 vs 11.1 +/- 0.6 microg/mL, P <or= .001, respectively) after adjustment for
      differences in height, weight, and fat-free mass as covariates. Men had lower
      plasma adiponectin concentrations than women in both Korean (P = .041) and
      Western adults (P < .001). Plasma adiponectin levels are lower in Korean than age
      , sex-, and body mass index-matched white adults, whereas fasting plasma FFA are
      not different. To the extent that adipogenic factors account for ethnic
      differences in metabolic disease risk, our data suggest that differences in the
      regulation of adiponectin may predispose toward greater metabolic abnormalities
      in Asians than whites at comparable BMI levels.

PMID- 19154964
TI  - Radiation dose to patients from radiopharmaceuticals. Addendum 3 to ICRP
      Publication 53. ICRP Publication 106. Approved by the Commission in October 2007.
AB  - In this report, the Commission provides biokinetic and dosimetric models for 33
      radiopharmaceuticals, as well as recommendations related to breast feeding for
      mothers who have undergone a nuclear medicine investigation. The report is based
      on Addenda 3-9 to Publication 53. Addenda 3-7 have been available on the ICRP
      website (www.icrp.org) as interim reports. The work has been carried out by a
      Joint Task Group of ICRP Committees 2 and 3. This publication provides biokinetic
      models, absorbed doses, and effective doses for the following
      radiopharmaceuticals: 11C-acetate; 11C-amino acids; 11C-brain receptor
      substances; 11C-methionine; 18F-amino acids; 18F-FET; 18F-FDG; 111In-monoclonal
      antibodies/fragments; 123I-fatty acids (BMIPP, IPPA); 123I-monoclonal
      antibodies/fragments; 131I-monoclonal antibodies/fragments; and 201Tl-ion. The
      publication also provides realistic maximum models for 11C- and 18F-substances,
      for which no specific models are available.

PMID- 19154969
TI  - We've come a long way.

PMID- 19154970
TI  - Feline myocardial disease. 1: Classification, pathophysiology and clinical
      presentation.

PMID- 19154971
TI  - Surgical management of blocked cats. Which approach and when?

PMID- 19154972
TI  - Treatment choices for oral cancer in cats. What is possible? What is reasonable?

PMID- 19154973
TI  - Idiopathic inflammatory bowel disease in cats. Rational treatment selection.

PMID- 19154974
TI  - Treatment of feline herpesvirus-1 associated disease in cats with famciclovir and
      related drugs.
AB  - BACKGROUND: Feline herpesvirus 1 (FHV-1) is a common cause of ocular and upper
      respiratory disease in cats and kittens, and a potential cause of eosinophilic
      dermatitis. HYPOTHESIS: The systemic anti-herpes drug, famciclovir (Famvir;
      Novartis), would be effective in the clinical management of disease attributable
      to FHV-1, including conjunctivitis, keratitis, corneal sequestra, rhinosinusitis
      and FHV-1 associated dermatitis. CLINICAL OUTCOME: Oral famciclovir was used to
      treat signs considered referable to FHV-1 in 10 cats: four had primary ocular
      disease, two had rhinosinusitis and four had FHV-1 associated dermatitis.
      Patients treated in Australia (five cats) and Europe (one cat) were given 62.5 mg
      of famciclovir once or twice daily. Four cats treated in the USA were given 125
      mg three times daily. Famciclovir was uniformly well tolerated and, in all cases,
      had a positive impact on the patient's condition. The apparent improvement in
      lesions was superior to what had been achieved previously using other therapeutic
      strategies. One cat with severe destructive rhinosinusitis was significantly
      improved by a 4-month course of famciclovir in combination with antibacterials.
      Corneal sequestra detached in two out of three cats treated; cats with ocular
      signs were qualitatively more comfortable, with reduced clinical signs and an
      improved appearance of the eyes. Critically, oral famciclovir therapy was
      considered more convenient than topical ocular therapy. All four cats with FHV-1
      associated dermatitis improved substantially, although relapse occurred
      subsequently in three patients. A further cat with presumptive FHV-1 associated
      dermatitis responded to topical aciclovir cream before famciclovir could be
      sourced. CONCLUSIONS: Famciclovir appears to be a promising systemic drug for
      treating diseases associated with FHV-1 infection. More rigorous clinical trials
      are required to optimise the dosing regimen for safe and effective specific anti
      herpes treatment in feline clinical medicine.

PMID- 19154975
TI  - Point: Cesium-131: ready for prime time.

PMID- 19154976
TI  - Counterpoint: Cesium-131: not ready for prime time.

PMID- 19154979
TI  - Prediction of seed migration after transperineal interstitial prostate
      brachytherapy with I-125 free seeds.
AB  - PURPOSE: The present study was undertaken to determine the incidence and
      predictors of seed migration after transperineal interstitial prostate
      brachytherapy using I-125 free seeds. METHODS AND MATERIALS: Between September
      2004 and November 2007, 158 patients who underwent transperineal interstitial
      prostate brachytherapy as monotherapy for clinical T1/T2 carcinoma of the
      prostate gland were reviewed. Implants had been performed with standard
      techniques. All 158 patients underwent followup radiographs (orthogonal chest
      radiographs, a kidney-ureter-bladder radiograph, and a posteroanterior pelvic
      radiograph) to assess the presence of seed migration at 3 months after
      transperineal interstitial prostate brachytherapy. Patient characteristics and
      treatment status were recorded. Univariate and multivariate analyses were
      performed to identify predictors of seed migration. RESULTS: Seed migration
      occurred in 35 of 158 patients (22.2%). Univariate analyses revealed that
      preoperative prostate volume estimated by transrectal ultrasound, the number of
      needles, the number of seeds implanted, and the presence or absence of pubic arch
      interference (PAI) were significantly associated with seed migration. These
      results indicated that larger prostate glands were more likely to have seed
      migration. However, the absolute difference in prostate size was not overly
      impressive (22.4 vs. 26.3cm(3)). Multivariate analysis revealed that the number
      of seeds implanted and the presence or absence of PAI were significant predictors
      of seed migration. CONCLUSION: The number of seeds implanted and the presence or
      absence of PAI provide the most predictive information on seed migration.

PMID- 19154980
TI  - Epithelium, tear down this wall!
AB  - The presence of bacteria within epithelial-lined compartments, such as the lung,
      elicits rapid recruitment of innate immune cells. In this issue of Cell Host &
      Microbe, Chun and Prince (2009) report that epithelial cells facilitate this
      process by reorganizing their intercellular junctions to enhance immune cell
      transmigration.

PMID- 19154981
TI  - The distinct roles of JAM-A in reovirus pathogenesis.
AB  - Despite their fundamental role in host defense, many components of epithelial and
      endothelial tight junctions serve as viral receptors. In this issue of Cell Host
      & Microbe, Antar et al. (2009) provide striking in vivo evidence that the broadly
      expressed reovirus receptor JAM-A plays a specific role in reovirus
      dissemination.

PMID- 19154982
TI  - Cholesterol paves the way for topically applied viricides.
AB  - Sexually transmitted viral infections have the potential to be prevented and
      treated by topical viricides. Here, Wu et al. (2009) demonstrate that cholesterol
      conjugated small interfering RNAs (siRNAs) targeting a cellular receptor combined
      with an antiviral siRNA when topically applied to mucosal tissue blocked lethal
      herpes virus infections in mice.

PMID- 19154983
TI  - Getting the bugs out of the immune system: do bacterial microbiota "fix"
      intestinal T cell responses?
AB  - Proinflammatory T helper 17 (Th17) cells control infections caused by microbial
      pathogens. Surprisingly, several recent reports now reveal that symbiotic gut
      bacteria modulate Th17 cell differentiation and function in the gastrointestinal
      tract. As various autoimmune and allergic disorders are mediated by uncontrolled
      T cell responses, immune regulation by the microbiota may have direct
      implications for human health.

PMID- 19154984
TI  - Caught in the act: intravital multiphoton microscopy of host-pathogen
      interactions.
AB  - Intravital multiphoton microscopy provides a unique opportunity to discover and
      characterize biological phenomena in the natural context of living organisms.
      Here we provide an overview of multiphoton microscopy with particular attention
      to its application for studying host-pathogen interactions.

PMID- 19154985
TI  - Helicobacter pylori CagA phosphorylation-independent function in epithelial
      proliferation and inflammation.
AB  - CagA, a major virulence factor of Helicobacter pylori (Hp), is delivered into
      gastric epithelial cells and exists in phosphorylated and nonphosphorylated
      forms. The biological activity of the phosphorylated form is well established;
      however, function(s) of the nonphosphorylated form remain elusive. Here, we
      report that a conserved motif in the C-terminal region of CagA, which is distinct
      from the EPIYA motifs used for phosphorylation and which we designate CRPIA
      (conserved repeat responsible for phosphorylation-independent activity), plays
      pivotal roles in Hp pathogenesis. The CRPIA motif in nonphosphorylated CagA was
      involved in interacting with activated Met, the hepatocyte growth factor
      receptor, leading to the sustained activation of phosphatidylinositol 3
      kinase/Akt signaling in response to Hp infection. This in turn led to the
      activation of beta-catenin and NF-kappaB signaling, which promote proliferation
      and inflammation, respectively. Thus, nonphosphorylated CagA activity contributes
      to the epithelial proliferative and proinflammatory responses associated with
      development of chronic gastritis and gastric cancer.

PMID- 19154986
TI  - RP105 facilitates macrophage activation by Mycobacterium tuberculosis
      lipoproteins.
AB  - RP105, phylogenetically related to Toll-like receptor (TLR)-4, is reported to
      facilitate B cell activation by the TLR4-agonist lipopolysaccharide (LPS)--but to
      limit LPS-induced cytokine production by antigen-presenting cells. Here, we show
      that the role of RP105 extends beyond LPS recognition and that RP105 positively
      regulates macrophage responses to Mycobacterium tuberculosis (Mtb) lipoproteins.
      Mtb-infected RP105(-/-) mice exhibited impaired proinflammatory cytokine
      responses associated with enhanced bacterial burden and increased lung pathology.
      The Mtb 19 kDa lipoprotein induced release of tumor necrosis factor in a manner
      dependent on both TLR2 and RP105, and macrophage activation by Mtb lacking mature
      lipoproteins was not RP105 dependent. Thus, mycobacterial lipoproteins are RP105
      agonists. RP105 physically interacted with TLR2, and both RP105 and TLR2 were
      required for optimal macrophage activation by Mtb. Our data identify RP105 as an
      accessory molecule for TLR2, forming part of the receptor complex for innate
      immune recognition of mycobacterial lipoproteins.

PMID- 19154987
TI  - TLR2-induced calpain cleavage of epithelial junctional proteins facilitates
      leukocyte transmigration.
AB  - Recruitment of polymorphonuclear leukocytes (PMNs) into the lungs in response to
      inhaled pathogens is initiated by epithelial signaling, the activation of toll
      like receptors (TLRs), and the production of the chemokine interleukin-8. To
      reach the site of infection, PMNs must be mobilized through epithelial junctions.
      Here, we demonstrate that Ca(2+) fluxes generated by TLR2 signals activate
      calpains, Ca(2+)-dependent cysteine proteases. These activated calpains cleave
      the transmembrane junctional proteins occludin and E-cadherin without breaching
      the integrity of the epithelial barrier. Calpain inhibitors decrease PMN
      transepithelial migration in response to TLR2 agonists both in vitro and in a
      mouse model of P. aeruginosa infection. Thus, TLR2 signaling in the airway not
      only induces chemokine expression to recruit PMNs, but also initiates cleavage of
      junctional proteins to accommodate transmigration of the recruited PMNs.

PMID- 19154988
TI  - Junctional adhesion molecule-A is required for hematogenous dissemination of
      reovirus.
AB  - Diverse families of viruses bind immunoglobulin superfamily (IgSF) proteins
      located in tight junctions (TJs) and adherens junctions of epithelium and
      endothelium. However, little is known about the roles of these receptors in the
      pathogenesis of viral disease. Junctional adhesion molecule-A (JAM-A) is an IgSF
      protein that localizes to TJs and serves as a receptor for mammalian reovirus. We
      inoculated wild-type (WT) and isogenic JAM-A(-/-) mice perorally with reovirus
      and found that JAM-A is dispensable for viral replication in the intestine but
      required for systemic dissemination. Reovirus replication in the brain and
      tropism for discrete neural regions are equivalent in WT and JAM-A(-/-) mice
      following intracranial inoculation, suggesting a function for JAM-A in reovirus
      spread to extraintestinal sites. JAM-A promotes reovirus infection of endothelial
      cells, providing a conduit for the virus into the bloodstream. These findings
      indicate that a broadly expressed IgSF viral receptor specifically mediates
      hematogenous dissemination in the host.

PMID- 19154989
TI  - Virus-induced unfolded protein response attenuates antiviral defenses via
      phosphorylation-dependent degradation of the type I interferon receptor.
AB  - Phosphorylation-dependent ubiquitination and degradation of the IFNAR1 chain of
      the type I interferon (IFN) receptor is regulated by two different pathways, one
      of which is ligand independent. We report that this ligand-independent pathway is
      activated by inducers of unfolded protein responses (UPR), including viral
      infection, and that such activation requires the endoplasmic reticulum-resident
      protein kinase PERK. Upon viral infection, activation of this pathway promotes
      phosphorylation-dependent ubiquitination and degradation of IFNAR1, specifically
      inhibiting type I IFN signaling and antiviral defenses. Knockin of an IFNAR1
      mutant insensitive to virus-induced turnover or conditional knockout of PERK
      prevented IFNAR1 degradation, whether UPR-induced or virus-induced, and restored
      cellular responses to type I IFN and resistance to viruses. These data suggest
      that specific activation of the PERK component of UPR can favor viral
      replication. Interfering with PERK-dependent IFNAR1 degradation could therefore
      contribute to therapeutic strategies against viral infections.

PMID- 19154990
TI  - Durable protection from Herpes Simplex Virus-2 transmission following
      intravaginal application of siRNAs targeting both a viral and host gene.
AB  - A vaginal microbicide should prevent pathogen transmission without disrupting
      tissue barriers to infection. Ideally, it would not need to be applied
      immediately before sexual intercourse, when compliance is a problem. Intravaginal
      administration of small interfering RNA (siRNA) lipoplexes targeting Herpes
      Simplex Virus Type 2 (HSV-2) genes protects mice from HSV-2. However, protection
      is short-lived, and the transfection lipid on its own unacceptably enhances
      transmission. Here, we show that cholesterol-conjugated (chol)-siRNAs without
      lipid silence gene expression in the vagina without causing inflammation or
      inducing interferons. A viral siRNA prevents transmission within a day of
      challenge, whereas an siRNA targeting the HSV-2 receptor nectin-1 protects for a
      week, but protection is delayed for a few days until the receptor is
      downmodulated. Combining siRNAs targeting a viral and host gene protects mice
      from HSV-2 for a week, irrespective of the time of challenge. Therefore,
      intravaginal siRNAs could provide sustained protection against viral
      transmission.

PMID- 19154991
TI  - Recombinant viral vaccines expressing merozoite surface protein-1 induce antibody
      and T cell-mediated multistage protection against malaria.
AB  - Protecting against both liver and blood stages of infection is a long-sought goal
      of malaria vaccine design. Recently, we described the use of replication
      defective viral vaccine vectors expressing the malaria antigen merozoite surface
      protein-1 (MSP-1) as an antimalarial vaccine strategy that elicits potent and
      protective antibody responses against blood-stage parasites. Here, we show that
      vaccine-induced MSP-1-specific CD4(+) T cells provide essential help for
      protective B cell responses, and CD8(+) T cells mediate significant antiparasitic
      activity against liver-stage parasites. Enhanced survival is subsequently seen in
      immunized mice following challenge with sporozoites, which mimics the natural
      route of infection more closely than when using infected red blood cells. This
      effect is evident both in the presence and absence of protective antibodies and
      is associated with decreased parasite burden in the liver followed by enhanced
      induction of the cytokine IFN-gamma in the serum. Multistage immunity against
      malaria can thus be achieved by using viral vectors recombinant for MSP-1.

PMID- 19154992
TI  - Vocational outcomes of an integrated supported employment program for individuals
      with persistent and severe mental illness.
AB  - We examined the effectiveness of an integrated supported employment (ISE)
      program, which augments Individual Placement & Support (IPS) with social skills
      training (SST) in helping individuals with SMI achieve and maintain employment. A
      total of 163 participants were randomly assigned to three vocational
      rehabilitation programs: ISE, IPS, and traditional vocational rehabilitation
      (TVR). After fifteen months of services, ISE participants had significantly
      higher employment rates (78.8%) and longer job tenures (23.84 weeks) when
      compared with IPS and TVR participants. IPS participants demonstrated better
      vocational outcomes than TVR participants. The findings suggested that ISE
      enhances the outcomes of supported employment, endorsing the value of SST in
      vocational rehabilitation.

PMID- 19154993
TI  - Synthesis and structural analysis of a series of D-glucose derivatives as low
      molecular weight gelators.
AB  - Low molecular weight gelators are an interesting new type of compounds that are
      important in supramolecular chemistry and advanced materials. Previously, we had
      synthesized several acyl derivatives of methyl 4,6-O-benzylidene-alpha-D
      glucopyranoside and found that a number of terminal acetylene-containing esters
      are good gelators. To understand the structure requirement of the acyl chains, we
      synthesized a series of analogs containing different functional groups including
      aryl, alkenyl, and halogen derivatives. X-ray crystal structures of a monoester
      and a diester derivative were also obtained to help understand the relationship
      between structure and gelation. For good gelation properties, the carboxyl
      derivatives should possess alkyl groups containing a terminal acetylene group and
      aryl derivatives.

PMID- 19154994
TI  - Diabetes, women, and development.

PMID- 19154995
TI  - Diabetes in women: the global perspective.
AB  - The prevalence of diabetes, and type 2 diabetes in particular, in women is
      increasing worldwide, although it is more pronounced in low-income countries.
      This increase is mostly due to population ageing and the ubiquitous rise in
      prevalence of obesity. Some of this rise is potentially preventable through
      lifestyle changes. A higher proportion of deaths in women than in men is
      attributable to diabetes. This article provides an overview of the specificities
      of diabetes in women and the implications of diabetes onset shifting to women of
      reproductive age.

PMID- 19154996
TI  - Coenzyme Q10 supplementation during pregnancy reduces the risk of pre-eclampsia.
AB  - OBJECTIVE: To assess whether supplementation with Coenzyme Q10 (CoQ10) during
      pregnancy reduces the risk of pre-eclampsia. METHODS: Women at increased risk of
      pre-eclampsia were enrolled in a randomized, double-blind, placebo-controlled
      trial. Women were assigned to receive 200 mg of CoQ10 or placebo daily from 20
      weeks of pregnancy until delivery. The primary outcome was rate of pre-eclampsia.
      Statistical analyses were by intention-to-treat. RESULTS: Of the 235 women
      enrolled in the trial, 118 were randomized to receive CoQ10 and 117 received a
      placebo. A total of 197 (83.8%) women were followed-up. The overall rate of pre
      eclampsia was 20% (n=47). Thirty women (25.6%) in the placebo group developed pre
      eclampsia compared with 17 women (14.4%) in the CoQ10 group, and this reduction
      was significant (P=0.035) (relative risk [RR] 0.56; 95% confidence interval [CI],
      0.33-0.96). CONCLUSION: Supplementation with CoQ10 reduces the risk of developing
      pre-eclampsia in women at risk for the condition.

PMID- 19154997
TI  - The 50-g glucose challenge test and pregnancy outcome in a multiethnic Asian
      population at high risk for gestational diabetes.
AB  - OBJECTIVE: To evaluate the 50-g glucose challenge test (GCT) on pregnancy outcome
      in a multiethnic Asian population at high risk for gestational diabetes (GDM).
      METHODS: GCT was positive if the 1-hour plasma glucose level was >or=7.2 mmol/L.
      GDM was diagnosed by a 75-g glucose tolerance test using WHO (1999) criteria. Of
      the 1368 women enrolled in the study, 892 were GCT negative, 308 were GCT false
      positive, and 168 had GDM. Pregnancy outcomes were extracted from hospital
      records. Multivariable logistic regression analysis was performed with GCT
      negative women as the reference group. RESULTS: GCT false-positive status was
      associated with preterm birth (adjusted odds ratio [AOR] 2.1; 95% CI, 1.2-3.7)
      and postpartum hemorrhage (AOR 1.7; 95% CI, 1.0-2.7). GDM was associated with
      labor induction (AOR 5.0; 95% CI, 3.3-7.5), cesarean delivery (AOR 2.2; 95% CI,
      1.6-3.2), postpartum hemorrhage (AOR 2.1; 95% CI, 1.2-3.7), and neonatal
      macrosomia (AOR 2.5; 95% CI, 1.0-6.0). CONCLUSION: GCT false-positive women had
      an increased likelihood of an adverse pregnancy outcome. The role and threshold
      of the GCT needs re-evaluation.

PMID- 19154998
TI  - Cultural perceptions, gestational diabetes, and development.
AB  - Women constitute half of the world's population, but a far larger percentage of
      the world's poor, particularly in low-income countries. The UN Millennium
      Declaration recognizes the link between growth, poverty reduction, and
      sustainable development, and the crucial role women play in achieving sustainable
      development. A child's future is interwoven with the life situation of its
      mother, most intimately so in the case of gestational diabetes. This article
      discusses the social and economic implications of the rapid growth of type 2
      diabetes and diabetes mellitus. It calls for culturally sensitive health policies
      and programs to address prevention and treatment of these conditions. Notions of
      conception, pregnancy, and well-being vary greatly among the world's 5000-6000
      cultures. The article illuminates this disparity, drawing on the author's
      research among indigenous people in Central Borneo. It concludes that culture
      specific perceptions must be incorporated in policies and programs that address
      the detrimental effects of diabetes on health and socioeconomic development.

PMID- 19154999
TI  - Pregnancy and diabetes scenario around the world: India.
AB  - Women with gestational diabetes mellitus (GDM) are at an increased risk of
      developing diabetes in the future, as are their offspring. GDM is not only of
      clinical relevance, but is also an important public health issue. A community
      based prospective study showed that the prevalence of GDM was 13.9%. We also
      observed that the frequency of GDM varied across urban, semi-urban, and rural
      areas. Based on multiple logistic regression analysis and taking the 3 areas into
      consideration, family history of diabetes, age greater than or equal to 25 years,
      and body mass index greater than or equal to 25 were found to have a significant
      independent association with GDM (P<0.001).

PMID- 19155000
TI  - Definition, size of the problem, screening and diagnostic criteria: who should be
      screened, cost-effectiveness, and feasibility of screening.
AB  - The epidemic of obesity and increased prevalence of diabetes necessitates
      reconsideration of its definition and screening by separating type 2 diabetic
      women from women with gestational diabetes to provide a better model of care. The
      unique problems concerning an undiagnosed type 2 diabetic woman are not major
      issues in the gestational diabetic woman. This review underscores the need for a
      unique diagnosis for women with moderate to severe hyperglycemia and/or other
      evidence of long-standing diabetes complications, and the urgent need for more
      intensive surveillance and treatment than is otherwise available for gestational
      diabetic women.

PMID- 19155001
TI  - Social and economic consequences of diabetes in women from low-income countries:
      a case study from Bangladesh.
AB  - Diabetes poses a serious threat to low-income countries such as Bangladesh. It is
      one of the leading causes of premature morbidity and mortality, and requires life
      long healthcare services. Women with diabetes are affected in all stages of their
      lives. Uniquely, diabetes affects the health of mothers and their unborn
      children. Poverty, ignorance, and gender discrimination adversely affect women
      with diabetes. However, the Diabetic Association of Bangladesh has played an
      increasingly effective role in providing comprehensive socio-medicare and life
      long follow-up of diabetic women, free of charge. This is reflected by the
      increasing attendance of women with diabetes, especially from rural areas.

PMID- 19155002
TI  - Polycystic ovary syndrome and abnormalities in glucose tolerance.
AB  - OBJECTIVES: To compare the prevalence of abnormal glucose tolerance (AGT) among
      women with polycystic ovary syndrome (PCOS) and controls, and assess risk factors
      associated with PCOS. METHOD: A fasting oral glucose tolerance test after
      ingestion of 75 g of glucose was administered to 264 women with and 116 without
      PCOS. Moreover, fasting glucose, insulin, and testosterone levels were measured
      in the women with PCOS. Body mass index (BMI), waist-to-hip ratio (WHR), and
      homeostasis model assessment-insulin resistance (HOMA-IR) were calculated for
      each woman with PCOS. RESULTS: The AGT prevalence was 14.4% in the PCOS group and
      11.2% in the control group (P=0.17). The women with both PCOS and AGT had
      significantly higher BMIs, WHRs, testosterone levels, and HOMA-IR values than
      those with normal glucose tolerance. CONCLUSION: While AGT was not associated
      with PCOS, the women with both PCOS and AGT were significantly more obese,
      hyperandrogenic, and insulin resistant than those with PCOS and normal glucose
      tolerance.

PMID- 19155003
TI  - Women's health in the 21st century.
AB  - Although women's health has been under-attended for most of the 20th century, it
      has gained international attention in recent decades. Medical and social research
      on heart disease, lung cancer, HIV/AIDS, and trachoma indicate that bio-socio
      variables affect women's health differently from men's. With regard to diabetes,
      data on pregnancy, diabetic ketoacidosis (DKA), depression, and heart disease
      corroborate the differentials between men and women. Data also indicate that
      social factors place diabetic women at a disadvantage regarding access to
      treatment and outcomes. Ascertaining the precise interactions that cause these
      differences and applying this information to policies and programs are imperative
      in the 21st century.

PMID- 19155004
TI  - Metabolic and endocrine effects of metformin and metformin plus cyclic
      medroxyprogesterone acetate in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the metabolic and endocrine effects of treatment with
      cyclic medroxyprogesterone acetate (MPA) plus metformin compared with metformin
      alone in women with PCOS. METHODS: In this prospective randomized study of women
      with PCOS, 20 women received 850 mg of metformin twice a day, and 20 women
      received 850 mg of metformin plus 5 mg of MPA twice a day. Body mass index,
      hormonal and lipid blood profiles, homocysteine blood level, and insulin
      sensitivities assessed by homeostasis model assessment (HOMA) were recorded at
      baseline and at 3 months. RESULTS: Total cholesterol levels decreased in the
      metformin plus MPA group (P=0.002) but did not change significantly in the
      metformin group (P=0.159). While homocysteine levels remained unchanged in the
      metformin plus MPA group, they increased significantly in the metformin group
      (P=0.002). CONCLUSION: There were no adverse effects of short-term cyclic MPA
      plus metformin treatment on metabolic parameters or insulin resistance in
      patients with PCOS over a 3-month treatment period.

PMID- 19155005
TI  - Perinatal mortality in pregestational diabetes.
AB  - Recent studies have found that the perinatal mortality (PNM) rate in pregnancies
      complicated by pregestational diabetes remains significantly higher than in the
      general population. These observations are probably related to lack of optimal
      glycemic control, and a significant proportion of unplanned pregnancies. The
      prevalence of pregnancies complicated by type 2 diabetes is increasing. Although
      these pregnancies are often perceived as a less serious condition, type 2
      diabetes appears to be associated with PNM rates that are at least as high as in
      type 1 diabetic pregnancies. This article reviews the epidemiology, etiology, and
      recommendations for prevention of PNM in pregnancies complicated by
      pregestational diabetes.

PMID- 19155006
TI  - Low birth weight and early weight gain in the metabolic syndrome: consequences
      for infant nutrition.
AB  - Emerging data indicate that being born small for gestational age (SGA) and rapid
      infant catch-up growth may play a significant role in the risk of developing type
      2 diabetes (T2DM) and the metabolic syndrome (MS) many years later in life. The
      impact of these perinatal T2DM and MS risk factors may be more important than
      genetics in some parts of the world, including low-income countries.
      Breastfeeding for 3-6 months is associated with reduced risk of developing
      insulin resistance and the metabolic syndrome. Promotion of fast growth in SGA
      infants by nutrient-enriched formula increases risk of hypertension and the
      metabolic syndrome. While waiting for better knowledge of how to combat T2DM and
      MS with early-life interventions, breastfeeding should be recommended and
      enforced whenever possible, keeping in mind the health and nutritional status of
      the mother. Furthermore, promotion of fast weight gain in SGA infants by nutrient
      enriched formula feeding should be used with caution. However, growth limitation
      by restriction of nutrition in SGA infants below general recommendations should
      not be recommended.

PMID- 19155007
TI  - Women, gender equality, and diabetes.
AB  - Discussion of women, gender equality, and diabetes should be placed in the
      context of United Nations mandates on women's health which highlight the need for
      equal access to information, prevention activities, services, and care across the
      life cycle. Gender differences and inequalities have been identified in relation
      to causes and consequences of diabetes and access to services and support between
      women and men, and among different groups of women. Appropriate gender-sensitive
      policy responses, including research and data collection, need to be developed.
      The recent United Nations resolution on diabetes provides an opportunity to
      strengthen the focus on women and diabetes.

PMID- 19155008
TI  - Obstetric outcomes of women with intracranial neoplasms.
AB  - OBJECTIVE: To determine the obstetric outcomes of women diagnosed with a primary
      intracranial neoplasm prior to or during pregnancy and the puerperium. METHODS:
      Demographic data, neurologic, obstetric, and neonatal outcomes were extracted
      retrospectively from charts identified from two hospital databases. RESULTS:
      Twenty-two patients with 25 pregnancies were identified. Thirteen patients were
      diagnosed prior to pregnancy (group 1); tumor growth or recurrence during
      pregnancy occurred in 3 patients. Nine patients were diagnosed during pregnancy
      and the puerperium (group 2); 7 underwent neurosurgery at a mean gestational age
      of 27+/-5.7 weeks; 2 experienced permanent visual loss. Significantly more
      gliomas occurred in group 1, but there were significantly more meningiomas in
      group 2. Numbers of cesarean delivery, preterm delivery at less than 34 weeks,
      and NICU admission were higher in group 2 than group 1, but this was not
      statistically significant. CONCLUSION: Although not statistically significant,
      neurologic deterioration during pregnancy may be associated with cesarean
      delivery, preterm delivery, and NICU admission.

PMID- 19155009
TI  - Human resources for health in the low-resource world: collaborative practice and
      task shifting in maternal and neonatal care.

PMID- 19155010
TI  - Prevalence and impact on quality of life of lower urinary tract symptoms among a
      sample of employed women in Taipei: a questionnaire survey.
AB  - BACKGROUND: Previous studies about the prevalence and impact of lower urinary
      tract symptoms (LUTS) were focused on urinary incontinence or overactive bladder
      in the general population. Little research has been focused on the role that the
      workplace has in employed women's experiences with LUTS or the impact of LUTS on
      their health-related quality of life (HRQL). OBJECTIVES: To estimate the
      prevalence of LUTS among employed female nurses in Taipei and to compare the HRQL
      for nurses with and without LUTS. DESIGN: This study was a cross-sectional,
      questionnaire survey. SETTINGS: Three medical centers and five regional hospitals
      in Taipei were selected randomly. PARTICIPANTS: In the selected hospitals, 1065
      female nurses were selected randomly. Data analyses were based on 907 usable
      surveys. All participants were native Taiwanese; most of the female nurses were
      26-35 years of age (mean=31.02, SD=6.32), had normal body mass index, and had
      never given birth. Most nurses' bladder habits were poor or very poor and their
      personal habits of fluid consumption at work were inadequate. METHODS: Data were
      collected using the Taiwan Nurse Bladder Survey and the Short Form 36 Taiwan
      version. Chi-square tests were used to compare the prevalence rates of different
      LUTS for nurses in different age groups. Student's t-tests were conducted to
      compare the mean scores of HRQL for nurses with and without LUTS. RESULTS: Based
      on 907 usable surveys, 590 (65.0%) experienced at least one type of LUTS. The
      prevalence for different LUTS ranged from 8.0% to 46.5%. Nurses who reported LUTS
      also reported lower HRQL, more so on physical health than mental health, than
      nurses who did not report LUTS. CONCLUSIONS: Although most of the nurses in this
      study were young (< or =35 years) and nulliparous, LUTS were common among this
      group. The high prevalence rate of LUTS leads to concerns about nurses' possible
      dysfunctional voiding patterns and possible effects of working environment and
      poor bladder and personal habits on LUTS. Study results showed a possible
      negative impact of LUTS on nurses' physical health. Designing a continence
      related education program for this group is essential for delivering information
      about LUTS prevention and management.

PMID- 19155012
TI  - Iron, metabolic syndrome, nonalcoholic fatty liver disease and carotid
      atherosclerosis.

PMID- 19155011
TI  - Changes in remnant and high-density lipoproteins associated with hormone therapy
      and progression of coronary artery disease in postmenopausal women.
AB  - OBJECTIVE: This study examined the effect of hormone therapy (HT) on the plasma
      concentration of remnant lipoprotein cholesterol (RLP-C) and high-density
      lipoprotein (HDL) subpopulations and the contribution of HT-related changes in
      these lipoproteins to the progression of coronary heart disease (CHD) in
      postmenopausal women. METHODS: Study participants were 256 women who completed
      the Estrogen Replacement and Atherosclerosis (ERA) trial, a placebo-controlled,
      randomized trial that examined the effects of 3.2 years of conjugated equine
      estrogen (CEE, 0.625 mg/day) or CEE (0.625 mg/day) plus medroxyprogesterone
      acetate (MPA, 2.5mg/day) on postmenopausal women with established coronary
      atherosclerosis. Quantitative coronary angiography and plasma RLP-C and HDL
      subpopulations were assessed at baseline and at follow-up. RESULTS: Relative to
      placebo, both CEE and CEE+MPA caused a significant reduction in plasma RLP-C
      concentrations and a significant increase in alpha1 and alpha2 HDL
      subpopulations. However, in the HT-treated subjects, faster progression of
      coronary atherosclerosis was observed in women who experienced the greatest
      reductions in RLP-C and in prebeta1 HDL subpopulations. CONCLUSIONS: Our data
      suggest that individual variability in RLP-C and HDL subpopulation response to HT
      is a predictor of CHD progression. Lipoprotein response to HT may be an indirect
      marker of susceptibility to other harmful effect of HT in postmenopausal women
      with established CHD or an indication of formation of dysfunctional lipoproteins.

PMID- 19155013
TI  - The endothelial nitric oxide synthase -786 T>C polymorphism and the exercise
      induced blood pressure and nitric oxide responses among men with elevated blood
      pressure.
AB  - OBJECTIVE: A polymorphism (-786 T>C) in the promoter region of the endothelial
      nitric oxide synthase gene (eNOS) has important functional characteristics. We
      examined the influence of eNOS -786 T>C (rs2070744) on the BP and NO response to
      acute dynamic exercise. METHODS: Subjects (n=49, 43.7+/-1.4 yr) had pre- to Stage
      1 hypertension (145.6+/-1.5/85.9+/-1.1 mmHg). Volunteers performed three
      experiments; a non-exercise control session, and two cycle exercise bouts at 40%
      (LIGHT) and 60% (MODERATE) of peak oxygen consumption. Subjects wore an
      ambulatory BP monitor upon leaving the laboratory. NO was measured by
      chemiluminescence assay before (baseline), during, and after the experiments.
      eNOS genotypes were determined by polymerase chain reaction and restriction
      enzyme digestion. Repeated measure ANOVA tested if BP and NO differed over time
      among experiments and by eNOS genotypes (n=25, TT; n=24, TC/CC). RESULTS: Among
      carriers of the eNOS C(786) allele, systolic BP (SBP) was reduced 5.3+/-2.4 mmHg
      after MODERATE versus non-exercise control over 9h compared to those with the
      eNOS T786T genotype (p<0.05). Under these conditions, SBP tended to be lower
      4.6+/-2.9 mmHg after LIGHT (p=0.076). The exercise-induced diastolic BP and NO
      responses were not different from non-exercise control between eNOS genotype
      (p>0.05). CONCLUSION: Men who were carriers of the eNOS C(786) allele responded
      more favorably to the antihypertensive effects of aerobic exercise than men with
      the eNOS T786T genotype. The eNOS C(786) allele is associated with reduced eNOS
      gene transcription and promoter activity. Future work is needed to determine how
      exercise may override genetic predispositions to down regulate eNOS gene
      activity.

PMID- 19155014
TI  - A comparison of enhanced continuum FE with micro FE models of human vertebral
      bodies.
AB  - Continuum finite element (FE) models are standard tools for determination of
      biomechanical properties of bones and bone-implant systems. This study
      investigates the accuracy of an enhanced continuum FE model by taking muFE as the
      gold standard. The enhanced continuum models account for trabecular bone
      morphology (density and fabric) as well as for an anatomically correct cortical
      shell. Vertebral body slice models are extracted from high-resolution CT images
      using an algorithm proposed in [Pahr and Zysset, 2008b. From high-resolution CT
      data to FE models: development of an integrated modular framework. Computer
      Methods in Biomechanics and Biomedical Engineering, in press.]. Three different
      models are generated: the proposed enhanced density-fabric-based model with a
      subject-specific cortex and two classical isotropic density-only models, with and
      without explicit modeling of the cortical shell. The material property errors of
      the used morphology-elasticity relationship are minimized by using elasticity
      tensors from 60 cubical muFE models which are cropped from the trabecular
      centrums of the investigated vertebral bodies. Two different boundary conditions
      kinematic [Van Rietbergen et al., 1995. A new method to determine trabecular bone
      elastic properties and loading using micromechanical FE models. Journal of
      Biomechanics 28 (1), 69-81] and mixed [Pahr, D.H., Zysset, P.K., 2008a. Influence
      of boundary conditions on computed apparent elastic properties of cancellous
      bone. Biomechanics and Modeling in Mechanobiology 7, 463-476.]-are used in these
      FE models. After removal of the endplates, compressive and antero-posterior shear
      loading is applied on the investigated vertebral bodies. Individual error sources
      are studied in more detail by loading also the trabecular centrum (removed shell)
      and the cortical shell alone. It is found that the cortex-only models need a
      correction of the shell thickness when transforming from a voxel to a smooth
      description. The trabecular centrum alone gives too stiff and too soft a response
      using material calibration with kinematic and mixed boundary conditions,
      respectively. A comparison of the whole vertebral body stiffnesses shows that an
      orthotropic cancellous bone material calibrated with kinematic boundary
      conditions corresponds best with muFE. Taken together, the proposed enhanced
      homogenized surface-based FE model is structurally more accurate than density
      only models.

PMID- 19155015
TI  - A parametric approach to numerical modeling of TKR contact forces.
AB  - In vivo knee contact forces are difficult to determine using numerical methods
      because there are more unknown forces than equilibrium equations available. We
      developed parametric methods for computing contact forces across the knee joint
      during the stance phase of level walking. Three-dimensional contact forces were
      calculated at two points of contact between the tibia and the femur, one on the
      lateral aspect of the tibial plateau, and one on the medial side. Muscle
      activations were parametrically varied over their physiologic range resulting in
      a solution space of contact forces. The obtained solution space was reasonably
      small and the resulting force pattern compared well to a previous model from the
      literature for kinematics and external kinetics from the same patient. Peak
      forces of the parametric model and the previous model were similar for the first
      half of the stance phase, but differed for the second half. The previous model
      did not take into account the transverse external moment about the knee and could
      not calculate muscle activation levels. Ultimately, the parametric model will
      result in more accurate contact force inputs for total knee simulators, as
      current inputs are not generally based on kinematics and kinetics inputs from TKR
      patients.

PMID- 19155016
TI  - Dual-purpose gas chromatographic injection device for pressurized liquid and gas
      injection.
AB  - A dual-purpose gas chromatographic injection device, capable of injecting
      pressurized liquid sample of up to 5000 psig and gas sample with a volume as high
      as 5000 microL, has been successfully developed and implemented. The injection
      device is synergized by the effectiveness of a classical flash vaporization of a
      syringe injection and the reliability of a proven rotary valve. Depending on the
      matrix involved, this injection device employs either a commercially available
      four-port internal valve for liquid sampling or a six-port external valve for gas
      sampling, a modified removable needle used in standard liquid syringe, and an
      auxiliary flow stream that can be either mechanical or electronic flow controlled
      for solute transfer. For pressurized liquid, the device was found suitable of up
      to nC(16) hydrocarbon with no observable carry-over despite the injection device
      was operating at ambient temperature. A relative standard deviation of less than
      2% (n=20) was obtained for hydrocarbon compounds ranging from nC(8) to nC(16).
      For gas injection, the device performed well even under difficult chromatographic
      conditions such as with a low column inlet pressure of less than 1 psig. A
      relative standard deviation of less than 0.5% (n=10) was obtained for reactive
      sulfur compounds such as alkyl mercaptans. The device can be operated manually or
      automated with pneumatic or electrical actuator, is platform neutral, and can be
      moved amongst instruments without hardware modification as well as implemented
      for on-line or in situ applications. In this paper, the utility of the device was
      also demonstrated with selected GC applications of industrial significance.

PMID- 19155017
TI  - Surface modified capillary electrophoresis combined with in solution isoelectric
      focusing and MALDI-TOF/TOF MS: a gel-free multidimensional electrophoresis
      approach for proteomic profiling--exemplified on human follicular fluid.
AB  - Development of miniaturized analytical tools continues to be of great interest to
      face the challenges in proteomic analysis of complex biological samples such as
      human body fluids. In the light of these challenges, special emphasis is put on
      the speed and simplicity of newly designed technological approaches as well as
      the need for cost efficiency and low sample consumption. In this study, we
      present an alternative multidimensional bottom-up approach for proteomic
      profiling for fast, efficient and sensitive protein analysis in complex
      biological matrices. The presented setup was based on sample pre-fractionation
      using microscale in solution isoelectric focusing (IEF) followed by tryptic
      digestion and subsequent capillary electrophoresis (CE) coupled off-line to
      matrix assisted laser desorption/ionization time of flight tandem mass
      spectrometry (MALDI TOF MS/MS). For high performance CE-separation, PolyE-323
      modified capillaries were applied to minimize analyte-wall interactions. The
      potential of the analytical setup was demonstrated on human follicular fluid
      (hFF) representing a typical complex human body fluid with clinical implication.
      The obtained results show significant identification of 73 unique proteins
      (identified at 95% significance level), including mostly acute phase proteins but
      also protein identities that are well known to be extensively involved in
      follicular development.

PMID- 19155018
TI  - Studying the mechanism of RNA separations using RNA chromatography and its
      application in the analysis of ribosomal RNA and RNA:RNA interactions.
AB  - DNA/RNA chromatography presents a versatile platform for the analysis of nucleic
      acids. Although the mechanism of separation of double stranded (ds) DNA fragments
      is largely understood, the mechanism by which RNA is separated appears more
      complicated. To further understand the separation mechanisms of RNA using ion
      pair reverse phase liquid chromatography, we have analysed a number of dsRNA and
      single stranded (ss) RNA fragments. The high-resolution separation of dsRNA was
      observed, in a similar manner to dsDNA under non-denaturing conditions. Moreover,
      the high-resolution separation of ssRNA was observed at high temperatures (75
      degrees C) in contrast to ssDNA. It is proposed that the presence of duplex
      regions/secondary structures within the RNA remain at such temperatures,
      resulting in high-resolution RNA separations. The retention time of the nucleic
      acids reflects the relative hydrophobicity, through contributions of the nucleic
      sequence and the degree of secondary structure present. In addition, the analysis
      of RNA using such approaches was extended to enable the discrimination of
      bacterial 16S rRNA fragments and as an aid to conformational analysis of RNA.
      RNA:RNA interactions of the human telomerase RNA component (hTR) were analysed in
      conjunction with the incorporation of Mg2+ during chromatography. This novel
      chromatographic procedure permits analysis of the temperature dependent formation
      of dimeric RNA species.

PMID- 19155019
TI  - Electrophoretic characterization of gold nanoparticles functionalized with human
      serum albumin (HSA) and creatine.
AB  - The synthesis of composite nanoparticles consisting of a gold core coated with a
      human serum albumin (HSA)/creatine layer is described, and their possible
      application as novel drug carriers for brain delivery is discussed. In this
      paper, the effect of the concentration of creatine and HSA in the different
      formulations is studied by electrophoretic mobility measurements as a function of
      pH and ionic strength. Due to the permeable character of the coatings surrounding
      the gold cores, an appropriate analysis of their electrophoretic mobility must be
      addressed. Recent developments of electrokinetic theories for particles covered
      by soft surface layers have rendered possible the evaluation of the softness
      degree from raw electrophoretic mobility data. In the present contribution, the
      data are quantitatively analyzed on the basis of three theoretical models of the
      electrokinetics of soft particles. As a result, information is obtained on both
      the surface potential and the charge density of the surrounding layer. The three
      models used reproduce properly the experimental behavior, although Duval and
      Ohshima's calculations appear to yield a more accurate fit of the data. It is
      shown that the albumin/nanogold particles absorb large amounts of creatine. In
      addition, the low surface charge and the albumin layer are expected to make it
      possible to deliver the particles through the blood-brain barrier.

PMID- 19155020
TI  - Interpersonal problems associated with narcissism among psychiatric outpatients.
AB  - Narcissistic personality disorder is the subject of extensive discussion in the
      literature. Yet, the validity of this diagnostic category remains questionable.
      This is owed, in large part, to the relative absence of empirical work that has
      examined narcissism in clinical samples. Descriptions and findings from studies
      involving non-clinical samples suggest that narcissism is associated with
      considerable interpersonal impairment. The objective of the present study was to
      examine this possibility in a sample of psychiatric outpatients. Consecutively
      admitted patients (N=240) to a day treatment program completed measures of
      narcissism, interpersonal problems, and general psychiatric distress. Patients
      were categorized into high, moderate, and low narcissism groups. The groups were
      compared on overall interpersonal impairment, as well as on particular domains of
      interpersonal behavior. Treatment duration and discharge status were also
      compared among the three groups. Analysis of covariance and chi-square analyses
      were used. At baseline, higher levels of narcissism were significantly associated
      with greater interpersonal impairment. The interpersonal style of the more
      narcissistic patients was particularly characterized by domineering, vindictive,
      and intrusive behavior. At post-treatment, only the association between
      narcissism and intrusive behavior remained significant. Change in interpersonal
      difficulties following treatment did not differ significantly among the groups.
      However, failure to complete treatment was associated with narcissism. The
      results underscore the interpersonal impairment associated with narcissism and
      support the notion of narcissistic personality disorder as a valid diagnostic
      category.

PMID- 19155021
TI  - Increased depressive symptoms in menopausal age women with bipolar disorder: age
      and gender comparison.
AB  - OBJECTIVE: Emerging data suggest the menopausal transition may be a time of
      increased risk for depression. This study examines the course of bipolar disorder
      focusing on depressive symptoms in menopausal transition age women, compared to
      similar-aged men as well as younger adult women and men. METHODS: Outpatients
      with bipolar disorder were assessed with the systematic treatment enhancement
      program for bipolar disorder (STEP-BD) affective disorders evaluation and
      longitudinally monitored during naturalistic treatment with the STEP-BD clinical
      monitoring form. Clinical status (syndromal/subsyndromal depressive symptoms,
      syndromal/subsyndromal elevation or mixed symptoms, and euthymia) was compared
      between menopausal transition age women (n=47) and pooled similar-aged men (n=30)
      45-55 years old, younger women (n=48) and men (n=39) 30-40 years old. RESULTS:
      Subjects included 164 bipolar disorder patients (67 type I, 82 type II, and 15
      not otherwise specified), 34% were rapid cycling and 58% women. Bipolar II
      disorder/bipolar NOS was more common in women. Monitoring averaged 30+/-22
      months, with an average of 0.9+/-0.5 clinic visits/month. Menopausal age women
      had a significantly greater proportion of visits with depressive symptoms
      (p<0.05), significantly fewer euthymic visits (p<0.05) and no difference in
      proportion of visits with elevated/mixed symptoms compared to pooled comparison
      group. CONCLUSIONS: Menopausal transition age women with bipolar disorder
      experience a greater proportion of clinic visits with depressive symptoms
      compared to similarly aged men, and younger women and men with bipolar disorder.
      Further systematic assessment on the influence of the menopausal transition and
      reproductive hormones upon mood is needed to better inform clinical practice in
      treating women with bipolar disorder.

PMID- 19155022
TI  - Aicardi syndrome in a 47, XXY male neonate with lissencephaly and
      holoprosencephaly.
AB  - Aicardi syndrome (AS) is a rare neuro-ophthalmic disorder first described by Jean
      Aicardi in 1965 with a characteristic triad of corpus callosal agenesis (CCA),
      chorioretinal lacunae (CRL), and infantile spasms (IS). All known cases of AS
      have been sporadic and a responsible gene has not been identified. With 5
      exceptional males, potential X-linked dominant genetic mutation characterizes AS
      occurring almost exclusively in girls. Most of male AS cases were still debatable
      in diagnosis either for their 46 XY karyotype or too atypical presentations to
      fit the formerly stricter diagnostic criteria. We report a 47, XXY male neonate
      presenting some undisputable, but otherwise some regarded as atypical features in
      AS. We compare his distinctively clinical pictures with previously reported male
      cases and find CRL is less pathognomonic and lissencephaly appears frequently
      among male AS. Because of insufficient genetic and biochemical markers for
      definite diagnosis at this moment, we suggest the experience of a relatively rare
      male case would help to shed light on the underlying genetic pathogenesis of AS.

PMID- 19155023
TI  - Temporal variation of chlorophyll a concentration in the coastal waters affected
      by the Hebei Spirit oil spill in the West Sea of Korea.
AB  - Time series changes in chlorophyll a concentration before and after the Hebei
      Spirit oil spill that occurred in December 2007 were analyzed using NCEP wind and
      SeaWiFS/MODIS ocean color data. Prevailing southwesterly winds and
      northeast/southwestward tidal currents pushed the oil towards Korea's West Sea
      coast of Taean. After the oil spill, daily chlorophyll a concentration decreased
      about 45-50% compared to the normal condition before the oil spill, and this
      decrease continued for about two weeks. Monthly mean chlorophyll a concentration
      in December 2007 was lower compared to the average value for the same month
      between 1998 and 2007, but, in October and November 2007 before the spill and in
      January-February 2008 after the spill, the concentration value was higher than
      average for the same period between 1998 and 2007.

PMID- 19155024
TI  - Concentrations of polycyclic aromatic hydrocarbons and polychlorinated biphenyls
      in green-lipped mussel Perna viridis from Victoria Harbour, Hong Kong and
      possible human health risk.

PMID- 19155025
TI  - The chain length of lignan macromolecule from flaxseed hulls is determined by the
      incorporation of coumaric acid glucosides and ferulic acid glucosides.
AB  - Lignan macromolecule from flaxseed hulls is composed of secoisolariciresinol
      diglucoside (SDG) and herbacetin diglucoside (HDG) moieties ester-linked by 3
      hydroxy-3-methylglutaric acid (HMGA), and of p-coumaric acid glucoside (CouAG)
      and ferulic acid glucoside (FeAG) moieties ester-linked directly to SDG. The
      linker molecule HMGA was found to account for 11% (w/w) of the lignan
      macromolecule. Based on the extinction coefficients and RP-HPLC data, it was
      determined that SDG contributes for 62.0% (w/w) to the lignan macromolecule,
      while CouAG, FeAG, and HDG contribute for 12.2, 9.0, and 5.7% (w/w),
      respectively. Analysis of fractions of lignan macromolecule showed that the
      higher the molecular mass, the higher the proportion of SDG was. An inverse
      relation between the molecular mass and the proportion (%) CouAG+FeAG was found.
      Together with the structural information of oligomers of lignan macromolecule
      obtained after partial saponification, it is hypothesized that the amount of
      CouAG+FeAG present during biosynthesis determines the chain length of lignan
      macromolecule. Furthermore, the chain length was estimated from a model
      describing lignan macromolecule based on structural and compositional data. The
      average chain length of the lignan macromolceule was calculated to be three SDG
      moieties with CouAG or FeAG at each of the terminal positions, with a variation
      between one and seven SDG moieties.

PMID- 19155026
TI  - Inducible expression of a Nep1-like protein serves as a model trigger system of
      camalexin biosynthesis.
AB  - Camalexin, the major Arabidopsis phytoalexin, is synthesized in response to a
      great variety of pathogens. Specific pathogen-associated molecular patterns, such
      as Nep1-like proteins from oomycetes act as signals triggering the
      transcriptional activation of the camalexin biosynthetic genes. PaNie, a Nep1
      like protein from Pythiumaphanidermatum was expressed in Arabidopsis under the
      control of an ethanol-inducible promoter. This system was developed as a tool to
      study the regulation of camalexin biosynthesis. It allowed induction of camalexin
      preceded by strong transcriptional activation of the tryptophan and camalexin
      biosynthetic genes. In flowers and green siliques PaNie expression elicited only
      minor camalexin formation, indicating low capability for phytoalexin synthesis in
      reproductive organs in contrast to leaf and stem tissue.

PMID- 19155027
TI  - Meroditerpenoids from the southern Australian marine brown alga Sargassum fallax.
AB  - Chemical investigation of the southern Australian marine brown alga Sargassum
      fallax resulted in the isolation of three meroditerpenoids fallahydroquinone,
      fallaquinone and fallachromenoic acid together with the previously reported
      compounds sargaquinone [isolated and identified in a mixture with sargaquinoic
      acid], sargahydroquinoic acid, sargaquinoic acid and sargachromenol. As a result
      of this study the complete 2D NMR characterisation for sargaquinoic acid and
      sargahydroquinoic acid can now be reported for the first time. All structures
      were elucidated by detailed spectrometric analysis. Sargaquinoic acid and
      sargahydroquinoic acid displayed moderate antitumour activity.

PMID- 19155028
TI  - Fabacyl acetate, a germination stimulant for root parasitic plants from Pisum
      sativum.
AB  - A germination stimulant, fabacyl acetate, was purified from root exudates of pea
      (Pisum sativum L.) and its structure was determined as ent-2'-epi-4a,8a
      epoxyorobanchyl acetate [(3aR,4R,4aR,8bS,E)-4a,8a-epoxy-8,8-dimethyl-3-(((R)-4
      methyl-5-oxo-2,5-dihydrofuran-2-yloxy)methylene)-2-oxo-3,3a,4,5,6,7,8,8b
      decahydro-2H-indeno[1,2-b]furan-4-yl acetate], by 1D and 2D NMR spectroscopic,
      ESI- and EI-MS spectrometric, X-ray crystallographic analyses, and by comparing
      the (1)H NMR spectroscopic data and relative retention times (RR(t)) in LC-MS and
      GC-MS with those of synthetic standards prepared from (+)-orobanchol and (+)-2'
      epiorobanchol. The (1)H NMR spectroscopic data and RR(t) of fabacyl acetate were
      identical with those of an isomer prepared from (+)-2'-epiorobanchol except for
      the opposite sign in CD spectra. This is the first natural ent-strigolactone
      containing an epoxide group. Fabacyl acetate was previously detected in root
      exudates of other Fabaceae plants including faba bean (Vicia faba L.) and alfalfa
      (Medicago sativa L.).

PMID- 19155029
TI  - Cassane diterpenes from Caesalpinia bonduc.
AB  - Three cassane diterpene hemiketals, caesalpinolide-C, caesalpinolide-D,
      caesalpinolide-E and one cassane furanoditerpene were isolated from Caesalpinia
      bonduc. The molecular structures were elucidated using NMR spectroscopy in
      combination with IR, UV and mass spectral data and relative stereochemistries
      were determined through ROESY correlation. The isolated compounds were tested for
      their antiproliferative activity against MCF-7 (breast adenocarcinoma), DU145
      (prostate carcinoma), C33A (Cervical carcinoma) and Vero (African green monkey
      kidney fibroblast) cells.

PMID- 19155030
TI  - [Anhidrotic ectodermal dysplasia. Rehabilitation].
AB  - INTRODUCTION: Anhidrotic ectodermal dysplasia (EAD) is an inherited syndrome with
      an incidence of one per 100,000 live births and is characterized by
      hypotrichosis, anhidrosis or hypohidrosis, and oligodontia. Various treatment
      options for the dental rehabilitation of children presenting with this disease
      have been published. There is however no consensus on what age implants should be
      placed. Our purpose was to describe the disease and rehabilitation with early
      implants through two case reports. OBSERVATION: Our two patients, a brother and
      sister, aged 14 and 15 years respectively, presented with EAD, maxillary
      hypodontia, and mandibular anodontia. They benefited from an orthodontic surgical
      treatment followed by prosthetic treatment. We designed a removable prosthesis on
      mandibular implants for the boy when he was 14, which was later replaced by a
      fixed prosthesis on implants. We shifted the lateral maxillary incisors
      orthodontically to a canine position, then performed autologous bone grafting for
      the placement of six implants. The same bone graft technique was used for the
      sister to insert four maxillary implants. The follow-up after implant placement
      was 7 and 4years, respectively. On the latest follow-up, the results were stable,
      functional, and esthetic. DISCUSSION: Dental implants are a reliable oral
      rehabilitation treatment for children presenting with ectodermal dysplasia.

PMID- 19155031
TI  - The vital signs of chronic disease management.
AB  - The vital signs of pulse rate, blood pressure, temperature and respiratory rate
      are the 'nub' of individual patient management. At the programmatic level, vital
      signs could also be used to monitor the burden and treatment outcome of chronic
      disease. Case detection and treatment outcome constitute the vital signs of
      tuberculosis control within the WHO's 'DOTS' framework, and similar vital signs
      could be adapted and used for management of chronic diseases. The numbers of new
      patients started on therapy in each month or quarter (new incident cases) are
      sensitive indicators for programme performance and access to services. Using
      similar reporting cycles, treatment outcomes for all patients can be assessed,
      the vital signs being: alive and retained on therapy at the respective facility;
      died; stopped therapy; lost to follow-up; and transferred out to another
      facility. Retention on treatment constitutes the prevalent number of cases, the
      burden of disease, and this provides important strategic information for rational
      drug forecasting and logistic planning. If case numbers and outcomes of chronic
      diseases were measured reliably and consistently as part of an integrated
      programmatic approach, this would strengthen the ability of resource-poor
      countries to monitor and assess their response to these growing epidemics.

PMID- 19155032
TI  - Drawing blood from young children: lessons learned from a trial in Ghana.
AB  - This paper reflects on lessons learned from a trial in Ghana assessing the impact
      of vitamin A supplementation on children's immune responses to tetanus and polio
      vaccines. There were more losses to follow-up than was anticipated at visits
      during which blood was drawn, owing to concerns or misconceptions about blood
      draw. The trial initially planned to recruit 960 children but had to recruit more
      because the proportion of infants lost to follow-up was greater than the
      anticipated 15%, resulting in a longer recruitment period. Of 1085 infants who
      were randomised into the trial, 767 (71%) completed follow-up at 6 months of age.
      It was notable that at the first (6 weeks) and fourth (6 months) visits at which
      blood was drawn, losses to follow-up were greater than at the second (10 weeks)
      and third (14 weeks) visits during which blood was not drawn. Losses to follow-up
      pose a threat to the validity of trials as there is a chance that those lost to
      follow-up may differ from those who remain in the trial. Monitoring losses to
      follow-up as they emerged and allowing mothers to witness the blood draw, as well
      as holding community meetings, helped to allay anxieties in the community.

PMID- 19155033
TI  - Outbreaks of hepatitis A among children in western India.
AB  - Hepatitis A in most developing countries is a sporadic childhood disease, but
      lately focal outbreaks have been observed among children in India. During 2004,
      we investigated a large-scale outbreak of hepatitis among children living in a
      residential colony in Daund Taluka of District Pune in the western region of
      India. In total, 123 overt and 56 sub-clinical cases were detected. All the
      patients were reactive for IgM antibodies against hepatitis A virus (IgM anti
      HAV) and were negative for IgM anti-hepatitis E virus, confirming HAV to be the
      etiological agent of the outbreak. Serum samples, feces and sewage samples were
      tested for HAV RNA and molecular characterization of the positives showed the
      presence of genotype IIIA. Further, IgM anti-HAV-positive sera from eight focal
      outbreaks were analyzed. The causative HAV in all these small-scale outbreaks
      also belonged to genotype IIIA, indicating the predominance of genotype IIIA in
      this region. This report of a large-scale, explosive outbreak of hepatitis A in
      Indian children once again emphasizes the need to evolve proper public health
      strategies, especially for vaccination, in countries in the transitional phase
      from hyperendemicity to intermediate endemicity.

PMID- 19155035
TI  - Comparison of three ELISAs for the routine diagnosis of human T-lymphotropic
      virus infection in a high-prevalence setting in Peru.
AB  - To compare three human T-lymphotropic virus (HTLV) ELISAs in a high-prevalence
      setting, we recruited 300 adults: 125 relatives of HTLV-infected subjects and 175
      patients with possible diagnoses of HTLV-associated diseases. Sera were tested
      with Platelia, Murex, and Ortho ELISA. Samples with positive or discordant ELISA
      underwent confirmatory Inno-Lia testing. Inno-Lia gave 85/300 HTLV-1-positive and
      1/300 HTLV-2-positive results. The positive predictive value was 98% for
      Platelia, and 100% for Murex and Ortho. Six samples had discordant ELISA; Murex
      gave one false-negative result, Ortho two and Platelia one. In high-prevalence
      settings, it is recommended to test samples with two ELISAs before considering
      them HTLV-seronegative.

PMID- 19155034
TI  - The distribution of insecticide resistance in Anopheles gambiae s.l. populations
      from Cameroon: an update.
AB  - Insecticides are a key component of vector-based malaria control programmes in
      Cameroon. As part of ongoing resistance surveillance efforts, Anopheles gambiae
      s.l. female mosquitoes were exposed to organochlorine (DDT), a carbamate
      (bendiocarb), an organophosphate (malathion), and three pyrethroids
      (deltamethrin, lambda-cyhalothrin and permethrin) in WHO bioassay test kits.
      Results indicated a higher level of resistance (reduced mortality and knockdown
      effect) to DDT and pyrethroids in populations of A. gambiae s.s. than in A.
      arabiensis. The West and East African knockdown resistance (kdr) mutations were
      found in both species but at much higher frequencies in A. gambiae s.s. The West
      Africa kdr mutant was also more frequent in the A. gambiae S form than in the M
      form. No resistance to bendiocarb and malathion was found. Carbamate and
      organophosphorous compounds could thus be used as alternatives in locations in
      Cameroon where pyrethroid-resistant populations are found.

PMID- 19155036
TI  - Spatially variant regularization of lateral displacement measurement using
      variance.
AB  - The purpose of this work is to confirm the effectiveness of our proposed
      spatially variant displacement component-dependent regularization for our
      previously developed ultrasonic two-dimensional (2D) displacement vector
      measurement methods, i.e., 2D cross-spectrum phase gradient method (CSPGM), 2D
      autocorrelation method (AM), and 2D Doppler method (DM). Generally, the
      measurement accuracy of lateral displacement spatially varies and the accuracy is
      lower than that of axial displacement that is accurate enough. This inaccurate
      measurement causes an instability in a 2D shear modulus reconstruction. Thus, the
      spatially variant lateral displacement regularization using the lateral
      displacement variance will be effective in obtaining an accurate lateral strain
      measurement and a stable shear modulus reconstruction than a conventional
      spatially uniform regularization. The effectiveness is verified through agar
      phantom experiments. The agar phantom [60mm (height) x 100 mm (lateral width) x
      40 mm (elevational width)] that has, at a depth of 10mm, a circular cylindrical
      inclusion (dia.=10mm) of a higher shear modulus (2.95 and 1.43 x 10(6)N/m(2),
      i.e., relative shear modulus, 2.06) is compressed in the axial direction from the
      upper surface of the phantom using a commercial linear array type transducer that
      has a nominal frequency of 7.5-MHz. Because a contrast-to-noise ratio (CNR)
      expresses the detectability of the inhomogeneous region in the lateral strain
      image and further has almost the same sense as that of signal-to-noise ratio
      (SNR) for strain measurement, the obtained results show that the proposed
      spatially variant lateral displacement regularization yields a more accurate
      lateral strain measurement as well as a higher detectability in the lateral
      strain image (e.g., CNRs and SNRs for 2D CSPGM, 2.36 vs 2.27 and 1.74 vs 1.71,
      respectively). Furthermore, the spatially variant lateral displacement
      regularization yields a more stable and more accurate 2D shear modulus
      reconstruction than the uniform regularization (however, for the regularized
      relative shear modulus reconstructions, slightly accurate, e.g., for 2D CSPGM,
      1.51 vs 1.50). These results indicate that the spatially variant displacement
      component-dependent regularization will enable the 2D shear modulus
      reconstruction to be used as practical diagnostic and monitoring tools for the
      effectiveness of various noninvasive therapy techniques of soft tissue diseases
      (e.g., breast, liver cancers). Application of the regularization to the
      elevational displacement will also increase the stability of a three-dimensional
      (3D) reconstruction.

PMID- 19155037
TI  - Efficient production of Rift Valley fever virus-like particles: The antiviral
      protein MxA can inhibit primary transcription of bunyaviruses.
AB  - Rift Valley fever virus (RVFV) is a highly pathogenic member of the family
      Bunyaviridae that needs to be handled under biosafety level (BSL) 3 conditions.
      Here, we describe reverse genetics systems to measure RVFV polymerase activity in
      mammalian cells and to generate virus-like particles (VLPs). Recombinant
      polymerase (L) and nucleocapsid protein (N), expressed together with a
      minireplicon RNA, formed transcriptionally active nucleocapsids. These could be
      packaged into VLPs by additional expression of viral glycoproteins. The VLPs
      resembled authentic virus particles and were able to infect new cells. After
      infection, VLP-associated nucleocapsids autonomously performed primary
      transcription, and co-expression of L and N in VLP-infected cells allowed
      subsequent replication and secondary transcription. Bunyaviruses are potently
      inhibited by a human interferon-induced protein, MxA. However, the affected step
      in the infection cycle is not entirely characterized. Using the VLP system, we
      demonstrate that MxA inhibits both primary and secondary transcriptions of RVFV.
      A set of infection assays distinguishing between virus attachment, entry, and
      subsequent RNA synthesis confirmed that MxA is able to target immediate early RNA
      synthesis of incoming RVFV particles. Thus, our reverse genetics systems are
      useful for dissecting individual steps of RVFV infection under non-BSL3
      conditions.

PMID- 19155038
TI  - Characterization of the 5'- and 3'-terminal subgenomic RNAs produced by a
      capillovirus: Evidence for a CP subgenomic RNA.
AB  - The members of Capillovirus genus encode two overlapping open reading frames
      (ORFs): ORF1 encodes a large polyprotein containing the replication-associated
      proteins plus a coat protein (CP), and ORF2 encodes a movement protein (MP),
      located within ORF1 in a different reading frame. Organization of the CP sequence
      as part of the replicase ORF is unusual in capilloviruses. In this study, we
      examined the capillovirus genome expression strategy by characterizing viral RNAs
      produced by Citrus tatter leaf virus (CTLV), isolate ML, a Capillovirus. CTLV-ML
      produced a genome-length RNA of approximately 6.5-kb and two 3'-terminal sgRNAs
      in infected tissue that contain the MP and CP coding sequences (3'-sgRNA1), and
      the CP coding sequence (3'-sgRNA2), respectively. Both 3'-sgRNAs initiate at a
      conserved octanucleotide (UUGAAAGA), and are 1826 (3'-sgRNA1) and 869 (3'-sgRNA2)
      nts with 119 and 15 nt leader sequences, respectively, suggesting that these two
      3'-sgRNAs could serve to express the MP and CP. Additionally, accumulation of two
      5'-terminal sgRNAs of 5586 (5'-sgRNA1) and 4625 (5'-sgRNA2) nts was observed, and
      their 3'-termini mapped to 38-44 nts upstream of the transcription start sites of
      3'-sgRNAs. The presence of a separate 3'-sgRNA corresponding to the CP coding
      sequence and its cognate 5'-terminal sgRNA (5'-sgRNA1) suggests that CTLV-ML
      produces a dedicated sg mRNA for the expression of its CP.

PMID- 19155039
TI  - AcMNPV EXON0 (AC141) which is required for the efficient egress of budded virus
      nucleocapsids interacts with beta-tubulin.
AB  - The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) encoded
      protein, EXON0 (AC141), is required for the efficient transport of nucleocapsids
      out of the nucleus for the production of budded virus (BV). To further elucidate
      the molecular mechanisms by which EXON0 regulates BV production, EXON0 was tagged
      at the N-terminus with 3x FLAG-6x His. Protein complexes were isolated by tandem
      affinity purification and potential EXON0 specific interacting protein partners
      were gel purified and identified by LC-MS/MS. This analysis showed that the
      cellular protein, beta-tubulin, co-purified with EXON0 which was confirmed by co
      immunoprecipitation. In addition, immunofluorescence showed that EXON0 and beta
      tubulin co-localized during virus infection. The microtubule inhibitors
      colchicine and nocodazole were used to treat AcMNPV infected Sf9 cells and
      results showed that BV production was reduced by over 85%. These data suggest
      that the egress of AcMNPV budded virus may be facilitated by the interaction of
      EXON0 with beta-tubulin and microtubules.

PMID- 19155040
TI  - Assessment of the pharmaceutical active compounds removal in wastewater treatment
      systems at enantiomeric level. Ibuprofen and naproxen.
AB  - The enantioselective degradation of ibuprofen and naproxen enantiomers was
      evaluated in five different wastewater treatment systems, including three
      constructed wetlands (vertical- and horizontal-flow configurations), a sand
      filter and an activated sludge wastewater treatment plant. In addition, injection
      experiments were carried out with racemic ibuprofen at microcosm- and pilot-scale
      constructed wetlands. Ibuprofen and naproxen have an asymmetric carbon atom and,
      consequently, two enantiomeric forms (i.e. S and R). The enantiomeric fraction
      (EF=S/(S+R)) in the raw sewage and effluents of various wastewater treatments
      were found to be compound-dependent (i.e. ibuprofen: EF(influent)=0.73-0.90,
      EF(effluent)=0.60-0.76; naproxen: EF(influent)=0.88-0.90, EF(effluent)=0.71
      0.86). Of the two chiral pharmaceuticals, naproxen was the only one whose
      effluent EF correlated with its removal efficiency (p<0.05). The lack of
      correlation found for ibuprofen was attributable to the fact that its
      enantioselective degradation kinetics were different under prevailing aerobic and
      anaerobic conditions. Injection experiments of ibuprofen in constructed wetlands
      at microcosm and pilot-scale followed similar trends. Hence, under prevailing
      aerobic conditions, S-ibuprofen degraded faster than R-ibuprofen, whereas under
      prevailing anaerobic conditions, the degradation was not enantioselective. In
      summary, the naproxen EF measurements in wastewater effluents show that naproxen
      is a suitable alternative for evaluating the removal efficiency of treatment
      systems because its enantioselective degradation is similar under prevailing
      aerobic and anaerobic conditions.

PMID- 19155041
TI  - Arsenate tolerance mechanism of Oenothera odorata from a mine population involves
      the induction of phytochelatins in roots.
AB  - We investigated the arsenate tolerance mechanisms of Oenothera odorata by
      comparing two populations [i.e., one population from the mine site (MP) and the
      other population from an uncontaminated site (UP)] via the exposure of hydroponic
      solution containing arsenate (i.e., 0-50 microM). The MP plants were
      significantly more tolerant to arsenate than UP plants. The UP plants accumulated
      more As in their shoots and roots than did the MP plants. The UP plants
      translocated up to 21 microg g(-1) of As into shoots, whereas MP plants
      translocated less As (up to 4.5 microg g(-1)) to shoots over all treatments. The
      results of lipid peroxidation indicated that MP plants were less damaged by
      oxidative stress than were UP plants. Phytochelatin (PC) content correlated
      linearly with root As concentration in the MP (i.e., [PCs](root)=1.69x[As](root),
      r(2)=0.945) and UP (i.e., [PCs](root)=0.89x[As](root), r(2)=0.979) plants. This
      relationship means that increased PC to As ratio may be associated with increased
      tolerance. Our results suggest that PC induction in roots plays a critical role
      in As tolerance of O. odorata.

PMID- 19155042
TI  - Electrochemical oxidation post-treatment of landfill leachates treated with
      membrane bioreactor.
AB  - Integration of membrane bioreactor (MBR) with electrochemical process was
      investigated as treatment of stabilized landfill leachates, collected from Djebel
      Chekir (Tunisia). Results showed that at optimum conditions for the membrane and
      with organic loading rates of 1.9 and 2.7g COD L(-1)d(-1), MBR treated effluent
      is still colouring and contains high COD and ammonia concentrations. In order to
      reduce these high pollutant concentrations, electrochemical oxidation process
      using Ti/Pt, graphite and PbO(2) electrodes, was tested as effluent post
      treatment. Ti/Pt electrodes showed the best performance. COD, ammonia and colours
      removals were affected by the current density (J) and treatment time (t). At
      optimal operational conditions (t=1h, J=4Adm(-2)), the final COD and total
      kjeldahl nitrogen concentrations (TKN) were 1000 and 86mgL(-1), respectively. The
      final treated wastewater COD, TKN, colours, pH meet the discharge standards in
      the sewer. The combination of MBR treatment process with electrochemical
      oxidation can be a technical suitable solution for stabilized landfill leachates
      treatment with an efficient reduction of different parameters, essentially COD
      (85%), TKN (94%), and colour(436) (99%).

PMID- 19155043
TI  - Antifeedant, larvicidal and pupicidal activities of Atalantia monophylla (L)
      Correa against Helicoverpa armigera Hubner (Lepidoptera: Noctuidae).
AB  - Antifeedant, larvicidal and pupicidal activities of hexane, chloroform and ethyl
      acetate extracts of Atlantia monophylla leaf were studied against third instar
      larvae of Helicoverpa armigera. All the extracts showed feeding deterrent,
      larvicidal and pupicidal effects in a dose dependent manner. Significant
      antifeedant, larvicidal and pupicidal activities were observed only in hexane
      extract. The hexane extract was subjected to fractionation using silica gel
      column chromatography. Twelve fractions were obtained. Ninth fraction showed good
      antifeedant, larvicidal, pupicidal activities and disrupted adult emergence.
      LC(50) value was at 384.57 ppm for larval mortality. The active fraction at 1000
      ppm concentration had 100% pupal mortality.

PMID- 19155044
TI  - Integration of nanofiltration and biological degradation of textile wastewater
      containing azo dye.
AB  - The anaerobic biological azo dyes reduction process was successfully applied to
      decolourization of the concentrates from the nanofiltration treatment of real
      textile effluents. The anaerobic phase was followed by aerobic oxidation aimed at
      the destruction of the aromatic amine released from azo dye. In the first
      experiment sequential batch reactor (SBR) combining both the anaerobic and
      aerobic phase in one unit was used. In the second one the anaerobic stage was
      separated from the aerobic one. The anaerobic phase fulfilled its aim
      (decolourization) in both systems (over 90%). In opposite, the aromatic amine was
      completely degraded in the aerobic reactor (two-sludge system), whereas the
      orthanilic acid was not degraded (during the aerobic phase) in SBR reactor. The
      COD reduction was also higher in the two-sludge system than in SBR.

PMID- 19155045
TI  - The endocrine disrupting activity of surface waters and of wastewater treatment
      plant effluents in relation to chlorination.
AB  - The present study investigated the biological quantification of estrogenic
      activity in the effluent of a wastewater treatment plant (WWTP) and in the
      recipient river in north-western Italy. Samples of the WWTP effluent and those of
      river water upstream and downstream the WWTP were taken from September 2006 to
      May 2007. The effluent was evaluated in the presence and absence of chlorination.
      The E-screen assay, with human estrogens receptor-positive MCF-7 BUS breast
      cancer cells, was performed on samples after solid-phase extraction to determine
      the total estrogenic activity by measuring the 17beta-estradiol equivalent
      quantity (EEQ). In order to study the correlation between estrogenicity and
      toxicity, untreated samples were also assayed with the acute toxicity test
      Microtox. Furthermore, to determine the efficiency of the chlorination process,
      all the samples were analysed for disinfection by-products (trihalomethanes) and
      Escherichia coli. The mean EEQs were 5.0 ng/L (+/-6.1 ng/L) upstream of the
      plant, 6.7 ng/L (+/-7.4 ng/L) downstream from the plant and 23.3 ng/L (+/-20.4
      ng/L) in the WWTP effluent. The difference between upstream and downstream of the
      treatment plant was not significant. Chlorinated water samples had lower
      estrogenic activity and E. coli concentrations, but had greater toxicity and
      higher trihalomethane concentrations. Estrogenic activity was not correlated with
      toxicity. These results suggest that the WWTP effluent had little impact on the
      estrogenic activity of the recipient river.

PMID- 19155046
TI  - Trace element content and molecular biodiversity in the epiphytic moss Leptodon
      smithii: two independent tracers of human disturbance.
AB  - This paper focuses on chemical composition of the epiphytic moss Leptodon
      smithii, gathered on Quercus ilex bark, assessed in seven sites located in urban
      and extra-urban/remote areas of southern Italy, a poorly surveyed geographic
      area. The concentrations of Cr, Cu, Pb and Zn in moss tissue are generally more
      abundant in moss gathered in the urban sites; among extra-urban/remote sites
      Valle delle Ferriere showed the highest metal concentrations, mostly related to
      an industrial activity occurred in the past. L. smithii chemistry seems
      influenced by airborne dust locally enhanced by erosion phenomena, long-range
      transport of pollutants and marine aerosols. Element content in moss is compared
      with genetic variability of L. smithii estimated in the same sites. Pearson's
      correlation coefficient between gene diversity and total element load (r=-0.851;
      p=0.03) suggests that anthropogenic pressure, determining habitat disturbance and
      fragmentation, leads both to genetic impoverishment consequent to population
      shrink, and to a higher accumulation in moss tissues, as a consequence of
      increased airborne major/trace elements. Thus, the coupled evaluation of chemical
      composition in mosses and gene diversity may prove a useful tool to highlight
      environmental disturbance in a gradient of land use.

PMID- 19155047
TI  - Increasing the resolution of the Broad Spectrum Revolution in the Southern
      Levantine Epipaleolithic (19-12 ka).
AB  - We analyze terminal Pleistocene archaeofaunal diversity trends in the Southern
      Levant by examining eight Epipaleolithic (ca. 19-12ka) assemblages from the
      Western Galilee/Mt. Carmel, Israel subregion. We test predictions from a Broad
      Spectrum Revolution model of the population dynamics of human foragers and their
      prey. The study emphasizes control over geographic variability and archaeological
      recovery and recording methods, as we analyze a time series that samples the
      Epipaleolithic more fully than have previous studies. This provides a new
      opportunity to examine human population and economic change in the long-term
      transition to sedentism and agriculture. We use the Mantel test to evaluate the
      significance of temporal trends in body-size-based big game diversity, as well as
      in diversity of small game prey types. Results demonstrate a highly significant
      decline through time in the relative abundance of medium and large big game,
      measured relative to small big game. This suggests that the apparent "gazelle
      specialization" by Late Epipaleolithic (Natufian) hunters reflects longer-term
      anthropogenic overexploitation of the largest prey types in the spectrum. While
      large and medium big game abundance declined, our results show small game
      increased in economic importance over time. Considered with associated climate
      change data, the results provide substantial support for the hypothesis that
      local human populations expanded rapidly in size after the Last Glacial Maximum
      (LGM). We suggest that following the post-LGM population pulse, human foragers
      adopted a shifting series of intensification strategies mediated by changes in
      residential mobility.

PMID- 19155048
TI  - Temporal variations of radon concentration in the saturated soil of Alpine
      grassland: the role of groundwater flow.
AB  - Radon concentration has been monitored from 1995 to 1999 in the soil of the Sur
      Fretes ridge (French Alps), covered with snow from November to April.
      Measurements were performed at 70 cm depth, with a sampling time of 1 h, at two
      points: the summit of the ridge, at an altitude of 1792 m, and the bottom of the
      ridge, at an altitude of 1590 m. On the summit, radon concentration shows a
      moderate seasonal variation, with a high value from October to April (winter),
      and a low value from May to September (summer). At the bottom of the ridge, a
      large and opposite seasonal variation is observed, with a low value in winter and
      a high value in summer. Fluctuations of the radon concentration seem to be
      associated with temperature variations, an effect which is largely delusory.
      Indeed, these variations are actually due to water infiltration. A simplified
      mixing model is used to show that, at the summit of the ridge, two effects
      compete in the radon response: a slow infiltration response, rich in radon, with
      a typical time scale of days, and a fast infiltration of radon-poor rainwater. At
      the bottom of the ridge, similarly, two groundwater contributions compete: one
      slow infiltration response, similar to the response seen at the summit, and an
      additional slower response, with a typical time scale of about a month. This
      second slower response can be interpreted as the aquifer discharge in response to
      snow melt. This study shows that, while caution is necessary to properly
      interpret the various effects, the temporal variations of the radon concentration
      in soil can be understood reasonably well, and appear to be a sensitive tool to
      study the subtle interplay of near surface transfer processes of groundwater with
      different transit times.

PMID- 19155049
TI  - Soil metal concentrations and toxicity: associations with distances to industrial
      facilities and implications for human health.
AB  - Urban and rural areas may have different levels of environmental contamination
      and different potential sources of exposure. Many metals, i.e., arsenic (As),
      lead (Pb), and mercury (Hg), have well-documented negative neurological effects,
      and the developing fetus and young children are particularly at risk. Using a
      database of mother and child pairs, three areas were identified: a rural area
      with no increased prevalence of mental retardation and developmental delay
      (MR/DD) (Area A), and a rural area (Area B) and an urban area (Area C) with
      significantly higher prevalence of MR/DD in children as compared to the state
      wide average. Areas were mapped and surface soil samples were collected from
      nodes of a uniform grid. Samples were analyzed for As, barium (Ba), beryllium
      (Be), chromium (Cr), copper (Cu), Pb, manganese (Mn), nickel (Ni), and Hg
      concentrations and for soil toxicity, and correlated to identify potential common
      sources. ArcGIS was used to determine distances between sample locations and
      industrial facilities, which were correlated with both metal concentrations and
      soil toxicity. Results indicated that all metal concentrations (except Be and Hg)
      in Area C were significantly greater than those in Areas A and B (p< or =0.0001)
      and that Area C had fewer correlations between metals suggesting more varied
      sources of metals than in rural areas. Area C also had a large number of
      facilities whose distances were significantly correlated with metals,
      particularly Cr (maximum r=0.33; p=0.0002), and with soil toxicity (maximum
      r=0.25; p=0.007) over a large spatial scale. Arsenic was not associated with
      distance to any facility and may have a different anthropogenic, or natural
      source. In contrast to Area C, both rural areas had lower concentrations of
      metals, lower soil toxicity, and a small number of facilities with significant
      associations between distance and soil metals.

PMID- 19155050
TI  - Microbes influence the fractionation of arsenic in paddy soils with different
      fertilization regimes.
AB  - Sequential extraction procedures were used to investigate the influence of the
      microbes on the distribution of arsenic in a Chinese paddy soil under different
      long-term fertilization treatments. The paddy soil with four long-term
      fertilization treatments (CK, M, NPK and NPK+M) and three levels of arsenate
      addition (0, 50, 100 mg As kg(-1) dry soil), were selected to construct
      microcosms for laboratory incubation. After the incubation, soil samples were
      sequentially extracted to determine As in various fractions, i.e. water soluble
      (F0), exchangeable (F1), bound to carbonates (F2), bound to Fe and Mn oxides
      (F3), bound to organic matter and sulfides (F4), and residual (F5, mineral
      matrix). Results showed that most of the As was fixed by mineral matrix (F5,
      ratios ranging from 46.22% to 96.37%), followed by As bound to Fe and Mn oxides
      (F3, ratios ranging from 3.14% to 28.18%), and the ratios of the other four
      fractions (F0, F1, F2 and F4) were mostly less than 10%. The microbes in the
      paddy soil could make As transform from inactive fraction (F5) to relatively
      active fractions (F0, F1, F2 and F3) and thus increase its environmental risk.
      With the increase of the As addition levels and with the application of manure or
      chemical NPK fertilizers, As was distributed more in the relatively active
      fractions (F0, F1, F2, F3 and F4) in the paddy soil mediated by the microbes. In
      addition, Fe and Mn oxides could play an important role in decreasing the As
      leaching potential from the mineral matrix to soil solution and thus abate the As
      risk to human health.

PMID- 19155051
TI  - Metals contained and leached from rubber granulates used in synthetic turf areas.
AB  - The aim of this study was to quantify metals contained in and leached from
      different types of rubber granulates used in synthetic turf areas. To investigate
      the total content of metals, ca 0.5 g of material was added with HNO(3), HF and
      HClO(4) and microwave digested with power increasing from 250 W to 600 W.
      Leachates were prepared by extraction of about 5.0 g of material at room
      temperature for 24 h in an acidic environment (pH 5). Leaching with deionized
      water was also performed for comparison. Aluminium, As, Ba, Be, Cd, Co, Cr, Cu,
      Hg, Fe, Li, Mg, Mn, Mo, Ni, Pb, Rb, Sb, Se, Sn, Sr, Tl, V, W and Zn were
      quantified by high-resolution inductively coupled plasma mass spectrometry (HR
      ICP-MS) and ICP optical emission spectrometry (ICP-OES). Results indicated that
      the developed method was accurate and precise for the multi-element
      characterization of rubber granulates and leachates. The total amount and the
      amount leached during the acidic test varied from metal to metal and from
      granulate to granulate. The highest median values were found for Zn (10,229
      mg/kg), Al (755 mg/kg), Mg (456 mg/kg), Fe (305 mg/kg), followed by Pb, Ba, Co,
      Cu and Sr. The other elements were present at few units of mg/kg. The highest
      leaching was observed for Zn (2300 microg/l) and Mg (2500 microg/l), followed by
      Fe, Sr, Al, Mn and Ba. Little As, Cd, Co, Cr, Cu, Li, Mo, Ni, Pb, Rb, Sb and V
      leached, and Be, Hg, Se, Sn, Tl and W were below quantification limits. Data
      obtained were compared with the maximum tolerable amounts reported for similar
      materials, and only the concentration of Zn (total and leached) exceeded the
      expected values.

PMID- 19155052
TI  - Desertification? Northern Ethiopia re-photographed after 140 years.
AB  - A collection of sepia photographs, taken during Great Britain's military
      expedition to Abyssinia in 1868, are the oldest landscape photographs from
      northern Ethiopia, and have been used to compare the status of vegetation and
      land management 140 years ago with that of contemporary times. Thirteen repeat
      landscape photographs, taken during the dry seasons of 1868 and 2008, were
      analyzed for various environmental indicators and show a significant improvement
      of vegetation cover. New eucalypt woodlands, introduced since the 1950s are
      visible and have provided a valuable alternative for house construction and fuel
      wood, but more importantly there has also been locally important natural
      regeneration of indigenous trees and shrubs. The situation in respect to soil and
      water conservation measures in farmlands has also improved. According to both
      historical information and measured climatic data, rainfall conditions around
      1868 and in the late 19th century were similar to those of the late 20th/early
      21st century. Furthermore, despite a ten-fold increase in population density,
      land rehabilitation has been accomplished over extensive areas by large-scale
      implementation of reforestation and terracing activities, especially in the last
      two decades. In some cases repeat photography shows however that riparian
      vegetation has been washed away. This is related to river widening in recent
      degradation periods, particularly in the 1970s-1980s. More recently, riverbeds
      have become stabilized, and indicate a decreased runoff response. Environmental
      recovery programmes could not heal all scars, but this study shows that overall
      there has been a remarkable recovery of vegetation and also improved soil
      protection over the last 140 years, thereby invalidating hypotheses of the
      irreversibility of land degradation in semi-arid areas. In a highly degraded
      environment with high pressure on the land, rural communities were left with no
      alternative but to improve land husbandry: in northern Ethiopia such
      interventions have been demonstrably successful.

PMID- 19155053
TI  - Changes in a temperate estuary during the filling of the biggest European dam.
AB  - This study aimed to determine whether and how the disruption of river flow,
      during the filling of the Alqueva dam, influenced the variability of abiotic and
      biotic factors in the Guadiana estuary, particularly the abundance and
      distribution of anchovy eggs. River inflow was found to be the most important
      factor in determining abiotic and biotic variability in the Guadiana estuary.
      Seasonal patterns were obscured by long periods of low inflow (mid April to early
      December 2002), which caused marked changes in the estuary. The estuarine
      turbidity maximum zone was displaced towards the upper estuary, to at least 38 km
      from the river mouth, 8 to 16 km upstream from previous records. The dynamics of
      nutrient stoichiometry was also affected. In the upper and middle estuary, P was
      more potential limiting than N and potential Si limitation was only frequent on
      the coast, with direct and/or indirect influence in changing phytoplankton
      dynamics and composition. Previously, the upper estuary alternated between
      potential P limitation during winter, Si limitation during spring and mid summer
      and N limitation during mid summer and autumn. The flooding of vast areas in the
      catchment of the dam probably caused the increase of DSi concentrations, as well
      as maximal N and P loadings. The abundance of larval stages of anchovy decreased,
      putatively because estuarine productivity has also decreased. In April 2002 there
      was an uncontrolled discharge from the Alqueva dam, which reduced the abundance
      of anchovy eggs by 99.99%. It is suggested that dam managers should mimic, as
      much as possible, the natural river flow, in order to minimize the impact on
      downstream ecosystems. Management efforts should not be restricted to the areas
      upstream of the dam, but should also encompass the estuary and adjacent coastal
      area.

PMID- 19155054
TI  - Tropospheric H(2) budget and the response of its soil uptake under the changing
      environment.
AB  - Molecular hydrogen (H(2)) is an indirect greenhouse gas present at the trace
      level in the atmosphere. So far, the sum of its sources and sinks is close to
      equilibrium, but its large-scale utilization as an alternative energy carrier
      would alter its atmospheric burden. The magnitude of the emissions associated
      with a future H(2)-based economy is difficult to predict and remains a matter of
      debate. Previous attempts to predict the impact that a future H(2)-based economy
      would exert on tropospheric chemistry were realized by considering a steady rate
      of microbial-mediated soil uptake, which is currently responsible of ~80% of the
      tropospheric H(2) losses. Although soil uptake, also known as dry deposition is
      the most important sink for tropospheric H(2), microorganisms involved in the
      activity remain elusive. Given that microbial-mediated H(2) soil uptake is
      influenced by several environmental factors, global change should exert a
      significant effect on the activity and then, assuming a steady H(2) soil uptake
      rate for the future may be mistaken. Here, we present an overview of tropospheric
      H(2) sources and sinks with an emphasis on microbial-mediated soil uptake
      process. Future researches are proposed to investigate the influence that global
      change would exert on H(2) dry deposition and to identify microorganisms involved
      H(2) soil uptake activity.

PMID- 19155055
TI  - PCDD/Fs and dioxin-like PCBs in home-produced eggs from Belgium: levels,
      contamination sources and health risks.
AB  - This paper discusses the dioxin TEQ levels as determined by the chemically
      activated luciferase gene expression assay (CALUX) and by HRGC-HRMS in eggs,
      soils, faeces and kitchen waste samples obtained in the CONTEGG study. The
      samples were collected in each Belgian province at private homes and in small
      gardens where chickens are held. The CALUX levels for eggs sampled in autumn were
      higher than the levels in eggs obtained at the same locations in spring (median
      values of 5.86 and 4.08 pg CALUX TEQ/g fat, respectively). The total WHO-TEQ
      levels in eggs, determined by HRGC-HRMS, ranged from 3.29 to 95.35 pg TEQ/g fat
      in autumn and from 1.50 to 64.79 pg TEQ/g fat in spring. In the soils on which
      the chickens forage, levels of 2.51-11.35 pg I-TEQ/g in autumn and 2.00-7.86 pg I
      TEQ/g in spring were found. The congener pattern of PCDD/Fs in the eggs, soils
      and faeces was dominated by OCDD, in addition to 1,2,3,4,6,7,8-HeptaCDD, OCDF and
      1,2,3,4,6,7,8-HeptaCDF. The predominant dioxin-like PCBs were PCB118, PCB 105 and
      PCB 156. The dioxin-like PCBs contributed on average 47%, 14% and 20% to the
      total WHO-TEQ in eggs, soils and faeces, respectively. Kitchen waste samples were
      very low-contaminated with dioxin-like compounds. The present results showed a
      good agreement between egg and soil TEQ levels for PCDD/Fs but not for dioxin
      like PCBs. This study showed that current soil levels found in some private
      gardens do not lead to egg levels below the current EU maximal level of 6 pg
      total TEQ/g fat for dioxins and dioxin-like PCBs. The consumers of the analysed
      eggs attained 5-79% of the tolerable weekly intake (TWI) of 14 pg TEQ/kg bw for
      dioxins and dioxin-like PCBs by exposure to their home-produced eggs only.

PMID- 19155056
TI  - A 10 mg warfarin initiation nomogram is safe and effective in outpatients
      starting oral anticoagulant therapy for venous thromboembolism.
AB  - The optimal means of initiating warfarin therapy for acute venous thromboembolism
      in the outpatient setting remains controversial. We have previously demonstrated
      the efficacy of a 10 mg initiation nomogram in a randomized controlled trial;
      however, some clinicians remain reluctant to use this nomogram due to a fear of
      potential increased bleeding. To review the safety and efficacy of a 10 mg
      warfarin nomogram we conducted a retrospective cohort study of patients
      prospectively treated for venous thromboembolism according to a 10 mg nomogram in
      an outpatient thrombosis clinic. All patients received standard treatment with
      low molecular weight heparin for 5 to 7 days and warfarin for at least 3 months.
      Four-hundred and fourteen patients were included in the analysis, of whom 295
      (71%) fully adhered to the nomogram. In the whole cohort, 8 patients (1.9%)
      experienced recurrent thrombosis, 4 (0.97%) suffered a major bleeding event, and
      3 (0.72%) suffered a minor bleeding event. There were no deaths related to
      thrombosis or bleeding. Four patients (0.97%) died from unrelated causes. Twenty
      two (5.3%) patients experienced an INR > or =5.0 in the first 8 days of therapy,
      and none of these patients experienced a bleeding event. Eighty-four percent of
      patients achieved a therapeutic INR by day 5. In outpatients, a 10 mg nomogram
      results in timely achievement of a therapeutic INR with an acceptable incidence
      of bleeding and recurrent thromboembolism.

PMID- 19155057
TI  - A direct thrombin inhibitor, lepirudin, for thrombophilic patients with
      inoperable critical limb ischemia.

PMID- 19155058
TI  - Letter from Houston "So what part of 'stable disease' do you not understand?".

PMID- 19155059
TI  - Broca's area: nomenclature, anatomy, typology and asymmetry.
AB  - In this review, we (i) describe the nomenclature of Broca's area and show how the
      circumscribed definition of Broca's area is disassociated from Broca's aphasia,
      (ii) describe in detail how the gross anatomy of Broca's area varies between
      people, and how the definitions vary between studies, (iii) attempt to reconcile
      the findings of structural asymmetry of Broca's area with the differences in
      methodological approaches, (iv) consider the functional significance of
      cytoarchitectonic definitions of Broca's area, and (v) critically elucidate the
      significance of circumscribed regions of cortex for language lateralisation and
      language development. Contrary to what has previously been reported in the
      literature, asymmetry of Broca's area has not been reproducibly demonstrated,
      particularly on a gross morphological level. This may be due to major
      inconsistencies in methodology (including different anatomical boundaries,
      measurement techniques and samples studied) or that the sulcal contours defining
      Broca's area are so naturally variable between people making a standard
      definition difficult. Cytoarchitectonic analyses more often than not report
      leftward asymmetry of some component of area 44 and/or area 45. If a structural
      asymmetry of Broca's area does exist, it is variable, which differs from that of
      the functional asymmetry of language, which is more consistent. One reason for
      this might be that the link between cellular architecture, connectivity and
      language function still remains to be elucidated. There is currently no
      convincing explanation to associate asymmetry of Broca's area with the
      lateralisation of language.

PMID- 19155060
TI  - Recovery after open versus laparoscopic pyloromyotomy for pyloric stenosis: a
      double-blind multicentre randomised controlled trial.
AB  - BACKGROUND: A laparoscopic approach to pyloromyotomy for infantile pyloric
      stenosis has gained popularity but its effectiveness remains unproven. We aimed
      to compare outcomes after open or laparoscopic pyloromyotomy for the treatment of
      pyloric stenosis. METHODS: We did a multicentre international, double-blind,
      randomised, controlled trial between June, 2004, and May, 2007, across six
      tertiary paediatric surgical centres. 180 infants were randomly assigned to open
      (n=93) or laparoscopic pyloromyotomy (n=87) with minimisation for age, weight,
      gestational age at birth, bicarbonate at initial presentation, feeding type,
      preoperative duration of symptoms, and trial centre. Infants with a diagnosis of
      pyloric stenosis were eligible. Primary outcomes were time to achieve full
      enteral feed and duration of postoperative recovery. We aimed to recruit 200
      infants (100 per group); however, the data monitoring and ethics committee
      recommended halting the trial before full recruitment because of significant
      treatment benefit in one group at interim analysis. Participants, parents, and
      nursing staff were unaware of treatment. Data were analysed on an intention-to
      treat basis with regression analysis. The trial is registered with
      ClinicalTrials.gov, number NCT00144924. FINDINGS: Time to achieve full enteral
      feeding in the open pyloromyotomy group was (median [IQR]) 23.9 h (16.0-41.0)
      versus 18.5 h (12.3-24.0; p=0.002) in the laparoscopic group; postoperative
      length of stay was 43.8 h (25.3-55.6) versus 33.6 h (22.9-48.1; p=0.027).
      Postoperative vomiting, and intra-operative and postoperative complications were
      similar between the two groups. INTERPRETATION: Both open and laparoscopic
      pyloromyotomy are safe procedures for the management of pyloric stenosis.
      However, laparoscopy has advantages over open pyloromyotomy, and we recommend its
      use in centres with suitable laparoscopic experience.

PMID- 19155061
TI  - Laparoscopic versus open pyloromyotomy.

PMID- 19155062
TI  - Seasonal variations in lipid composition of the hydrothermal vent mussel
      Bathymodiolus azoricus from the Menez Gwen vent field.
AB  - Specimens of the hydrothermal mussel Bathymodiolus azoricus collected in Menez
      Gwen hydrothermal vent field (NE Atlantic) during 2002-2003 were examined for
      feeding patterns variations through three seasons. The fatty acid profile and
      lipid classes of the mussels were studied, together with the MODIS/AQUA-derived
      near-surface chlorophyll a to test the hypothesis that surface productivity might
      be related to the feeding patterns of this species. The lipid levels showed
      pronounced seasonal fluctuations with the highest values occurring in January and
      August. Seasonal variations in lipid classes and fatty acid composition of
      neutral and polar lipids in the mussels are presented. Differences in the fatty
      acid profile of lipid classes in different seasons suggest that the higher energy
      requirements in summer and winter were supplied by bacterial biomarkers omega7
      MUFA (monounsaturated fatty acids), whereas omega6 PUFA (polyunsaturated fatty
      acids) and NMI (non-methylene-interrupted) fatty acids predominated during the
      spring. The MODIS/AQUA data show marked seasonal variability and an anomalous
      peak during January of 2003, although this cannot be directly linked to lipid
      composition variation.

PMID- 19155063
TI  - The adsorption and lubrication behavior of synovial fluid proteins and
      glycoproteins on the bearing-surface materials of hip replacements.
AB  - The selectivity of synovial fluid protein adsorption onto ultra-high molecular
      weight polyethylene (UHMWPE) and alumina (Al(2)O(3)), and in particular the
      ability of glycoproteins to adsorb in the presence of all the other synovial
      fluid proteins, was investigated by means of fluorescence microscopy and gel
      electrophoresis (SDS-PAGE). The non-specific nature of protein adsorption from
      synovial fluid indicated that the lubrication of artificial hip-joint materials
      may not be attributable to a single protein as has been frequently suggested. The
      friction behavior of polyethylene (PE) sliding against Al(2)O(3) in solutions of
      bovine serum albumin (BSA), alpha-1-acid glycoprotein (AGP) and alpha-1
      antitrypsin (A1AT) was investigated by means of colloidal probe atomic force
      microscopy. BSA was shown to be a poorer boundary lubricant than the phosphate
      buffered saline used as a control. This was attributed to denaturation of the BSA
      upon adsorption, which provided a high-shear-strength layer at the interface,
      impairing the lubrication. Interestingly, both the glycoproteins AGP and A1AT,
      despite their low concentrations, improved lubrication. The lubricating
      properties of AGP and A1AT were attributed to adsorption via the hydrophobic
      backbone, allowing the hydrophilic carbohydrate moieties to be exposed to the
      aqueous solution, thus providing a low-shear-strength fluid film that lubricated
      the system. The amount of glycoprotein adsorbed on hydrophobic surfaces was
      determined by means of optical waveguide lightmode spectroscopy (OWLS), allowing
      conclusions to be drawn about the conformation of the glycan residues following
      adsorption.

PMID- 19155064
TI  - Periprosthetic tissue reactions observed at revision of total intervertebral disc
      arthroplasty.
AB  - Wear, wear particle induced inflammation, and osteolysis following total disc
      arthroplasty were, until recently, not thought to be present due to limited
      intervertebral motion and the lack of a synovial membrane between the lower
      lumbar vertebrae. The purpose of this study was to evaluate the periprosthetic
      tissue reactions associated with total disc arthroplasty revision surgery.
      Periprosthetic samples of fibrous tissue were collected in all patients during
      revision surgery of SB Charite III disc prostheses. Revision was indicated for
      intractable pain after an average of 8 years. Histological evaluation was
      performed in tissue samples of 16 patients using light microscopy and polarized
      light microscopy with a magnification of 100x. Polyethylene particles were
      detected in 15 of 16 patients. The smallest particles were the most numerate. A
      positive correlation was present between the number of particles per mm(2) and
      the extent of the chronic inflammatory reaction in the periprosthetic fibrous
      tissue. Osteolysis was observed in one patient. In the tissue samples containing
      polyethylene particles, TNF-alpha and IL-6 were determined by
      immunohistochemistry. TNF-alpha and IL-6 were co-expressed as a subset of
      mononuclear macrophages and giant cells.

PMID- 19155065
TI  - The effect of an rhBMP-2 absorbable collagen sponge-targeted system on bone
      formation in vivo.
AB  - Reparation of bone defects remains a major clinical and economic concern, with
      more than 3 million bone grafts performed annually only in the United States and
      the EU. The search for alternatives to autologous bone grafting led to the
      approval by the FDA of an absorbable collagen carrier combined with rhBMP-2 for
      the treatment of certain bone diseases and fractures. The present work is focused
      on the production of a collagen-targeted rhBMP-2 based system to improve bone
      formation. We produced a modified rhBMP-2 with only an additional collagen
      binding decapeptide derived from the von Willebrand factor and tested its
      affinity to collagen and its ability to induce ectopic bone formation in vivo
      when implanted in combination with absorbable collagen sponges or hydroxyapatite.
      The results showed not only that the rhBMP2-CBD had an increased affinity to
      collagen, but also that this binding was very stable during a prolonged period of
      time. In vivo experiments demonstrated that this rhBMP2-CBD maintained its
      osteoinductive activity, being capable of inducing new bone formation even at
      lower concentrations than native rhBMP-2. These results indicate that the
      combination of the fusion protein with absorbable collagen may be a suitable and
      safer alternative to rhBMP-2 for bone repair purposes.

PMID- 19155066
TI  - Expression, regulation and functional characterization of matrix
      metalloproteinase-3 of human trophoblast.
AB  - MMP-3 has been detected in human placenta and reduced expression of the enzyme
      was observed in invasive trophoblasts of patients with severe preeclampsia.
      However, detailed expression pattern, regulation and biological properties of the
      placental protease have not been elucidated so far. RT-PCR analyses, Western
      blotting and enzyme activity assays revealed that pro- and active form of MMP-3
      were predominantly expressed in purified first trimester villous trophoblasts, in
      invasive cytotrophoblasts of differentiating explant cultures and in
      trophoblastic SGHPL-4 cells. Accordingly, immunofluorescene of first trimester
      placental tissues detected MMP-3 mainly in villous and extravillous
      cytotrophoblasts. IL-1beta, an inducer of MMP-3 in decidual cells, increased
      secretion and activity of the protease in trophoblast supernatants in a dose- and
      time-dependent manner. IL-1beta-stimulated production of the enzyme was
      suppressed in the presence of inhibitors of MAPK and AKT signalling. Similar to
      recombinant MMP-3, MMP-3 in supernatants of IL-1beta-stimulated decidual stromal
      or SGHPL-4 cells degraded IGFBP-1 in vitro resulting in the appearance of
      cleavage products at approximately 25, 22, 17, 14 and 11kD. However, cleavage
      assays using recombinant MMP-2 suggested that the gelatinase may contribute to
      IGFBP-1 degradation in trophoblast supernatants. Despite its effects on MMP-3
      expression IL-1beta failed to significantly alter invasion of SGHPL-4 cells
      through Matrigel-coated transwells. In conclusion, the data suggest that invasive
      trophoblast cell models secrete bioactive MMP-3. Inducible expression of the
      protease involves MAPK and AKT signalling. In addition to the decidua, MMP-3 of
      trophoblasts may contribute to the regulation of the IGF system by degrading
      IGFBP-1.

PMID- 19155067
TI  - Therapy-related myelodysplastic syndrome with der(17)t(12;17)(q13;p13) as a new
      recurrent cytogenetic abnormality after treatment for chronic lymphocytic
      leukemia.
AB  - A 54-year-old male presented to our hospital for evaluation of peripheral
      lymphocytosis. He was initially diagnosed with chronic lymphocytic leukemia (CLL)
      and treated with six cycles of fludarabine, cyclophosphamide, and rituximab
      chemotherapy. Therapy-related myelodysplastic syndrome (t-MDS) was suspected
      approximately 2 years later; in addition, complex karyotypic abnormalities
      including 5q deletion, monosomy 7, and der(17)t(12;17)(q13;p13) were found
      repeatedly in the patient's chromosome studies. The chromosomal abnormality
      der(17)t(12;17)(q13;p13) is very rare in hematologic malignancies, and has been
      reported in only two patients with therapy-related acute myeloid leukemia (t
      AML). To our knowledge, this is the first report of t-MDS with
      der(17)t(12;17)(q13;p13) after treatment for CLL. In addition, we suggest that
      der(17)t(12;17)(q13;p13) should be considered a new recurrent, nonrandom
      chromosomal abnormality in patients with t-MDS/AML.

PMID- 19155068
TI  - Environmental properties of long-chain alcohols. Part 2: Structure-activity
      relationship for chronic aquatic toxicity of long-chain alcohols.
AB  - Daphnia magna reproduction tests were performed with C(10), C(12), C(14) and
      C(15) alcohols to establish a structure-activity relationship of chronic effects
      of long-chain alcohols. The data generation involved substantial methodological
      efforts due to the exceptionally rapid biodegradability of the test substances
      and the need to test as close as possible to their water solubility limits. Test
      concentrations were determined by GC-MS before and after test solution renewal.
      Whereas apparent toxicity based on survival and reproduction increased with
      increasing C-chain lengths up to C(14), observations of toxicity to C(15) alcohol
      were not in line with lower chain lengths due to the lack of toxicity below the
      level of water solubility. When omitting C(15), the slope of most (Q)SARs
      approach -1, being consistent with the expectation of a non-polar narcotic mode
      of action. Further testing at higher chain lengths is not sensible due to
      progressively lower solubility, at remaining biodegradability. Effects on
      mortality and reproduction are not expected below the level of water solubility.

PMID- 19155069
TI  - Suicide ideation across reproductive life cycle of women. Results from a European
      epidemiological study.
AB  - BACKGROUND: The aim of the present study is to compare suicide ideation among
      women in the pre-, peri-, and post-menopause using a cross-sectional household
      survey of non-institutionalised adults from six European countries. METHODS: In
      total, 8794 out of 21,425 respondents provided data for the following study. To
      use men as a comparison group, we defined three different groups of male
      subjects, based on the mean age of the women groups. RESULTS: We found an
      increased risk of suicide ideation among women in their peri-menopause compared
      with women in their pre- or post-menopause and men. This finding was independent
      of mood and anxiety disorders. LIMITATIONS: Some categories showed few
      individuals. The cross-sectional design of our study does not allow us to
      conclude causal relationship between variables. CONCLUSION: The occurrence of
      suicide ideation varies across the reproductive life cycle of women.

PMID- 19155070
TI  - Course of adherence to medication and quality of life in people with
      schizophrenia.
AB  - This study examined the relationship over time of adherence to anti-psychotic
      medication and quality of life in people with schizophrenia, taking into account
      effects of mediating variables. Data on on adherence, quality of life, attitude
      towards medication, side effects, symptom severity, and level of functioning at
      baseline and 1-year follow-up were obtained from 373 participants in a multi
      centre trial. Participants randomised to the intervention group were offered
      eight sessions of adherence therapy. Data were analysed via block recursive
      graphical modelling. Direct links between adherence and quality of life and
      effects across time were scarce and weak if present. However, indirect effects
      could be identified, i.e. adherence at baseline affected quality of life at
      follow-up via symptom severity and medication side effects. These findings
      underline associations between "traditional" clinical outcome parameters and
      quality of life. Adherence might have an impact on some of these clinical outcome
      dimensions, and this might indirectly affect quality of life across time.
      Overall, findings indicate that at present, there is no plausible explanatory
      model of adherence. This also has consequences for clinical practice since there
      is no compelling evidence on how to intervene effectively to improve adherence in
      people with schizophrenia.

PMID- 19155071
TI  - Induction of delayed-type hypersensitivity and interferon-gamma to Candida
      albicans and anti-hen-egg white lysozyme antibody as phenotypic markers of
      enhanced bovine immune response.
AB  - Delayed-type hypersensitivity (DTH) is a protective localized cell-mediated
      immune response (CMIR), primarily against intracellular pathogens. DTH is widely
      used in research to assess immune responsiveness and has been a valuable
      diagnostic test in commercial settings. In pigs and other species both antibody
      (AMIR) and CMIR have been considered as reliable phenotypic markers of selection
      programs for disease resistance. Therefore in cattle, it was also considered
      important to find antigen/adjuvant combinations capable of inducing AMIR and CMIR
      without interfering with diagnostic tests. The objectives of the present study
      were to evaluate the combined use of hen-egg white lysozyme (HEWL) and Candida
      albicans adjuvanted with Quil A in lactacting Holstein cows for the induction of
      anti-HEWL antibody, as well as DTH and IFN-gamma to C. albicans as phenotypic
      markers of enhanced immune responsiveness. Thirty one lactating Holstein cows
      were immunized with HEWL to induce antibody responses and C. albicans to
      sensitize for DTH. Two test antigens, candin and C. albicans whole cell (CaWC),
      were used to induce the effector phase of DTH. PBS was used as the negative
      control. In addition, two different skin sites (neck versus tail) were tested to
      evaluate differences in skin site responsiveness. C. albicans-induced IFN-gamma
      production, as an indicator of a type 1 response, was evaluated by ELISA.
      Microscopic evaluation of skin samples at DTH sites was performed in five
      randomly selected cows and these skin biopsies were scored based on inflammation
      and cell infiltration. Results demonstrated the presence of classical DTH
      response to C. albicans, in that DTH responses peaked at 24 h post-intradermal
      injections and cell infiltration was composed largely of mononuclear leukocytes,
      typical of DTH skin reactions in cattle. The only difference in test antigens was
      that DTH to candin showed a higher early response (6 h) than CaWC and a rapid
      decrease in inflammation from 24 to 48 h. The neck was significantly more
      sensitive than the tail skin-fold as a DTH test site. IFN-gamma was detected on
      days 14 and 21 post-immunization in plasma from blood incubated with candin.
      Significant primary and secondary anti-HEWL antibodies were also detected,
      indicating that this combination of test antigens could be used as phenotypic
      markers of immune responsiveness in cattle.

PMID- 19155072
TI  - Etiology of unilateral neural hearing loss in children.
AB  - OBJECTIVE: Unilateral sensorineural hearing loss (SNHL) can be caused by a
      variety of lesions of the inner ear and central nervous system. An inner hair
      cell or neural site of pathology must be suspected when otoacoustic emissions
      (OAEs) are present, and inconsistent with audiologic data. We reviewed unilateral
      neural hearing loss (UNHL) in children, to better understand its etiology,
      clinical and audiologic features. DESIGN: Retrospective series. SETTING: Tertiary
      pediatric center. METHODS: From a database of 480 children with unilateral SNHL,
      148 had OAE data. Patients with a neural pattern (present OAEs in the affected
      ear) were reviewed. OUTCOME MEASURES: Clinical course, audiologic data, imaging
      findings. RESULTS: Of 148 patients with OAE data, 11 (7.4%) had the unilateral
      neural phenotype. Most had stable, severe-to-profound loss in the affected ear.
      MRI determined an etiology in all 10 patients who received it. Absent cochlear
      nerves were remarkably common, being found in eight patients (73%). Tumors,
      previously unsuspected, were identified in the other two patients who received
      MRI. CONCLUSIONS: Cochlear nerve aplasia appears by far the most common cause of
      UNHL in children. As in adults, mass lesions must also be considered in children
      with unilateral SNHL with a neural pattern. As both lesions elude diagnosis on
      CT, MRI is the better modality for evaluating this condition.

PMID- 19155073
TI  - Effect of cardiogenic pulmonary edema on defibrillation efficacy.

PMID- 19155074
TI  - Revelation of Brugada electrocardiographic pattern during a febrile state
      associated with acute myocardial infarction.
AB  - The prevalence of the Brugada-type ECG and its natural history are still unclear.
      The Brugada syndrome is usually identified by a characteristic Brugada-type ECG
      that consists of ST elevation of a coved type in the precordial leads V1 to V3
      and ventricular fibrillation that can lead to sudden cardiac death, although
      affected individuals may have a normal ECG. Mutations in the cardiac sodium
      channel gene SCN5A, which encodes the alpha-subunit of the human cardiac voltage
      dependent Na+ channel (Na(v)1.5), are identified in 15-30% of patients with
      Brugada syndrome. Most SCN5A mutations lead to a 'loss-of-function' phenotype,
      reducing the Na+ current during the early phases of the action potential. Several
      nongenetic factors have been mentioned in the literature as possible inductors of
      the ECG pattern resembling Brugada syndrome. As such, a Brugada-type ECG may
      appear in some patients during febrile states and in those who are under the
      influence of cocaine and pharmaceutical drugs that have a sodium channel-blocking
      effect. It has been also reported chest pain and ST elevation Brugada pattern
      during febrile states. We present a case of revelation of Brugada pattern in a 69
      year-old Italian man during a febrile state associated with acute myocardial
      infarction. Also this report confirms that Brugada pattern should be considered
      as one of differential diagnoses when we examine the patients during a febrile
      state.

PMID- 19155075
TI  - The relationship between tumor necrosis factor-alpha, brain natriuretic peptide
      and atrial natriuretic peptide in patients with chronic heart failure.
AB  - BACKGROUND: Cytokines such as tumor necrosis factor-alpha (TNF) contribute to
      cardiac dysfunction in chronic heart failure (CHF). Brain natriuretic peptide
      (BNP) and atrial natriuretic peptide (ANP) are thought to reflect cardiac
      functional and structural damage. METHODS AND RESULTS: To study the relationship
      between BNP, ANP, and TNF, these parameters were measured in fasting venous blood
      samples of 25 CHF patients (age 66+/-2 years, pVO(2) 17.4+/-2.1 mL/kg/min, NYHA
      class 2.8+/-0.2, all mean+/-SEM) and 8 healthy controls (age 71+/-2 years).
      Patients with CHF had higher plasma levels of BNP (p<0.05), ANP (p<0.05),
      norepinephrine (p<0.01), and echocardiographic left ventricular end-diastolic
      diameter (LVEDD, p<0.05) compared to controls, whereas TNF and epinephrine were
      not significantly different. There were significant correlations between
      natriuretic peptides and markers of inflammation and myocardial dysfunction in
      CHF patients: BNP vs. TNF (r=0.64, p=0.0006), vs. LVEDD (r=0.59, p=0.0025); ANP
      vs. TNF (r=0.60, p=0.0016), vs. LVEDD (r=0.65, p=0.0006); TNF vs. LVEDD (r=0.57,
      p=0.004). After adjustment for NYHA, creatinine clearance, and age TNF correlated
      with BNP (all p=0.01) and ANP (all p<0.002). The cachectic CHF patients (n=7,>6%
      weight loss) had the highest BNP (p<0.001 vs. controls, p<0.05 vs. non-cachectic
      CHF) and ANP levels (p=0.01 vs. controls). Concentrations of uric acid,
      epinephrine, and norepinephrine also correlated with ANP and BNP. CONCLUSION: In
      CHF, TNF is closely related to BNP and ANP (independently of CHF severity and
      ventricular dysfunction), particularly in patients with cardiac cachexia. TNF may
      causally contribute to intrinsic cardiac dysfunction thereby stimulating BNP and
      ANP secretion.

PMID- 19155076
TI  - Quantitative analysis of intracoronary optical coherence tomography measurements
      of stent strut apposition and tissue coverage.
AB  - BACKGROUND: The introduction of optical coherence tomography (OCT) as an
      intracoronary imaging modality has allowed accurate assessment of strut
      apposition and neointimal tissue coverage. This study set out to assess the inter
      and intraobserver variability of measurements of acute stent apposition and strut
      tissue coverage using OCT. METHODS: Thirty patients were studied (14 immediately
      after stent implantation and 16 during follow-up angiography [mean of 4.7+/-2.8
      months]) using OCT (LightLab, Westford, Massachusetts, US). Data analysis was
      performed by 2 experienced observers. Struts were classified as "embedded",
      "protruding" or "malapposed" to the vessel well and recorded as percentage of
      total struts. Intimal coverage at follow-up was measured as the thickness of
      tissue covering each strut expressed in mum. Intra and interobserver variability
      was assessed by Bland-Altman plots and by calculation of the intraclass
      correlation coefficient (ICC). RESULTS: An average of 3967 struts was examined by
      each observer and, overall, 53.7% of struts was embedded, 36.4% protruding and
      9.9% malapposed. Low intraobserver variability for all measures of strut
      apposition was found, with repeatability coefficients that ranged between 5.1%
      and 9.3% and ICC exceeding 95% in all cases. Interobserver variability was also
      low (repeatability coefficients 6.6-10.8 and ICC>91.3%). Mean intimal thickness
      in the follow-up group was 172.5 microm. Bland-Altman plots demonstrated a low
      intraobserver and interobserver variability for intimal thickness, with
      repeatability coefficients 26.7 mum and 24.1 mum, respectively and ICC exceeding
      98.6% for both. CONCLUSIONS: Low intra and interobserver variability can be
      expected when analyzing OCT data for stent apposition and tissue coverage. This
      supports the validity of OCT as a clinical and research tool in the setting of
      intracoronary stent imaging.

PMID- 19155077
TI  - Heart rate dynamic during an exercise test in heart failure patients with
      different sensibilities of the carvedilol therapy: heart rate dynamic during
      exercise test.
AB  - BACKGROUND: Some trials suggest that the titration of Carvedilol is based on rest
      heart rate from 50 to 60 bpm and a target daily dose of 50 mg/day. AIM: To
      evaluate the heart rate dynamic in heart failure patients with different
      sensibilities of the Carvedilol therapy during an exercise test. METHODS:
      Patients were divided into four groups and submitted a treadmill cardiopulmonary
      exercise test: heart rate >60 bpm and Carvedilol<than 50 mg/day (30 patients)
      (non-optimized group); heart rate >60 bpm and Carvedilol > or =50 mg/day (19
      patients) (non-optimized low-sensibility); heart rate between 50 and 60 bpm and
      Carvedilol > or =50 mg/day (16 patients) (optimized); heart rate between 50 and
      60 bpm and Carvedilol<50 mg/day (10 patients) (optimized high-sensible group).
      RESULTS: The heart rate peak and the percentage of the peak heart rate in
      relation with the maximum heart rate predicted for age during the cardiopulmonary
      exercise test were the same between the non-optimized (128+/-13, bpm; 74+/-7%)
      and non-optimized low-sensibility (136+/-20, bpm; 78+/-8%) groups, and between
      the optimized (105+/-25, bpm; 60+/-13%) and optimized high-sensible (108+/-16,
      bpm; 62+/-8%) groups. The heart rate reserve was the same. CONCLUSION: The heart
      rate dynamic was almost the same between groups with rest heart rate >60 bpm and
      between groups <60 bpm, independently of the Carvedilol dose. Based on these
      findings, we propose a new method to titrate carvedilol therapy by the
      cardiopulmonary exercise test.

PMID- 19155078
TI  - Carotid body tumor.
AB  - Carotid body tumors are the most common paragangliomas of head and neck. Most of
      these tumors are benign with a small malignant potential. Although newer non
      invasive diagnostic modalities have significantly enhanced the diagnostic
      capabilities, controversy exists over adequate management of these rare tumors.
      In younger, healthy patients with no comorbidities, the best therapeutic strategy
      is a complete excision of the tumor. However, in less than ideal patient
      population modalities such as radiation and tumor embolization can be considered.
      Surgical advances have greatly decreased the mortality rates, but the morbidity
      rates secondary to cranial nerve injuries remain high.

PMID- 19155079
TI  - Stress cardiomyopathy: clinical and ventriculographic characteristics in 107
      North American subjects.
AB  - BACKGROUND: Stress cardiomyopathy (SCM) is a newly described reversible
      cardiomyopathy of largely unclear etiology. We studied SCM in a large cohort to
      gain further insights. METHODS: We retrospectively identified 114 cases of SCM
      from among 12,150 consecutive North American patients diagnosed as Troponin
      positive acute coronary syndrome, from January 2000 through December 2007, at two
      24-h coronary angioplasty-capable centers. Left ventriculographic wall
      contractility was analyzed and scored in 107 patients on the right anterior
      oblique view. RESULTS: In 107 patients (66+/-14 years, 99 females), variable
      regional contractility or "ballooning" was observed including: postero-basal, 1%;
      basal+mid-ventricular, 1%; diaphragmatic, 2%; localized apical, 2%; antero
      lateral, 11%; complete mid-ventricular, 29%; and classical variant, 54%. The
      localized and complete mid-ventricular variants (n=45, 40 females) had a younger
      median age at presentation (64 vs. 71 years, p=0.008) and higher median LV
      ejection fraction (45% vs. 35%, p=0.006) than the classical or tako-tsubo
      variants (n=58, 55 females) with similar baseline exposure to stressors, risk
      factor and in-hospital complications. Frequency of involvement and mean
      contractile score (dysfunction) of the antero-lateral segment was significantly
      (p<0.05) greater in the order, antero-lateral>diaphragmatic>apical>basal.
      CONCLUSION: From a single large cohort of SCM, evidence on significant individual
      variation in clinical and morphological pattern was confirmed. Frequency and
      vulnerability to transient dysfunction differs within segments with antero
      lateral involvement significantly greater than diaphragmatic, apical, basal
      anterior and basal-posterior LV segments. Further studies in phenotype should be
      undertaken for proper identification, classification and pathophysiological
      implications.

PMID- 19155080
TI  - Evidence that chronic alcohol exposure promotes intestinal oxidative stress,
      intestinal hyperpermeability and endotoxemia prior to development of alcoholic
      steatohepatitis in rats.
AB  - BACKGROUND/AIMS: Not all alcoholics develop liver disease (ALD). Thus, excessive
      ethanol consumption is necessary, but not sufficient, to induce alcoholic
      steatohepatitis (ASH) and ALD. Since endotoxemia is present in patients with ALD,
      it has been proposed that gut-derived, circulating endotoxin is the necessary co
      factor for ASH. But, it is not known whether endotoxemia is the consequence or
      the trigger for ALD. Accordingly, the aim of the current study was to determine
      whether endotoxemia occurs prior to development of ASH and whether gut leakiness
      is the primary cause of the endotoxemia in an animal model of ASH. METHODS: Time
      courses for development of gut hyperpermeability, nitric oxide production,
      oxidative injury to the gut, endotoxemia, and liver injury were assessed in rats
      during 10 weeks of daily alcohol gavage. RESULTS: Liver fat and serum
      transaminase increased after 2 weeks, but evidence of liver cell injury and
      inflammation (ASH) occurred after 8 weeks. Gut leakiness, intestinal oxidative
      injury, and endotoxemia occurred in weeks 2-4 and progressed thereafter.
      CONCLUSIONS: That alcohol-induced gut leakiness and endotoxemia preceded
      steatohepatitis indicates they are not the consequence of ALD. Our data support
      the hypothesis that gut leakiness resulting in endotoxemia is a key co-factor
      (trigger) for ASH.

PMID- 19155081
TI  - Infliximab monotherapy for severe alcoholic hepatitis and predictors of survival:
      an open label trial.
AB  - BACKGROUND/AIMS: Severe alcoholic hepatitis (AH) is associated with very high
      mortality. Tumor necrosis factor-alpha (TNF-alpha) contributes to the progression
      of AH and TNF-alpha antagonists like infliximab may help in ameliorating the
      severity and complications of AH. There is a scarcity of data regarding the
      safety and efficacy of infliximab monotherapy in the treatment of AH. We
      evaluated infliximab monotherapy in patients with severe AH. METHODS: Patients
      with severe AH (Maddrey's score>32) received a single dose of infliximab 5 mg/kg
      IV. The primary endpoint was survival assessed at one and two months. The
      secondary endpoints were reduction of the Maddrey's DF and development of any
      bacterial infections. Predictors of survival were assessed at admission and at
      day 7. RESULTS: Nineteen patients were enrolled in the study and received
      infliximab. By the end of one month two patients died resulting in 1-month
      survival of 17/19 (89%). By the end of two months four additional patients died
      resulting in 2-month survival of 68%. At the end of one and two months, compared
      to baseline, there was significant improvement in median values of Maddrey's DF
      (p<0.05). Median serum TNF-alpha levels decreased from 45 (range 11-19,880) at
      baseline to 20 (range 4-8600) pg/mL at 4 weeks (p=0.001). CRP levels, MELD score,
      and absolute neutrophil count decreased significantly. Five patients (26%)
      developed infection: three of them had pneumonia, while two developed a flare of
      pulmonary tuberculosis. Three patients recovered with treatment but two patients
      (10%) died (one with pneumonia leading to sepsis and the other of disseminated
      tuberculosis). Absence of hepatic encephalopathy at admission significantly
      predicted survival. Among patients who survived only 1/13 (8%) had hepatic
      encephalopathy at admission while among patients who died 4/6 (67%) had hepatic
      encephalopathy (p=0.017). Lille score and delta bilirubin at day 7 (DBD7)
      (defined as [baseline serum bilirubin minus serum bilirubin at day 7] x
      100/baseline serum bilirubin), also predicted 2-month mortality. The area under
      ROC curve of DBD7 values for predicting survival was 0.77 (95% CI 0.55-0.99).
      DBD7 of >7.5% best predicted survival in the patients (sensitivity 85%,
      specificity 67%, PPV 85%, NPV 67%, and overall accuracy 79%). CONCLUSIONS: In
      severe AH, single dose infliximab is associated with improvement in parameters of
      severity and survival. However, infection remains a concern. Hepatic
      encephalopathy at admission, Lille score and DBD7 predicted 2-month mortality.
      Large randomized controlled trials are needed before infliximab can be
      recommended for AH.

PMID- 19155082
TI  - The long-term follow-up after idiosyncratic drug-induced liver injury with
      jaundice.
AB  - BACKGROUND/AIMS: Chronic evolution after drug-induced liver injury (DILI) has
      been reported. How often this leads to liver-related morbidity and mortality is
      unexplored. METHODS: Patients who survived DILI and concomitant jaundice reported
      to the Swedish Adverse Drug Reaction Advisory Committee (1970-2004) were linked
      to the Swedish Hospital Discharge and Cause of Death Registries. RESULTS: Among
      the 712 survivors, 27 could not be retrieved but 685 patients could be linked to
      the registries, 392 females (57.2%) and 293 males (42.8%) median age 58 (41-74),
      a mean follow-up of 10 years. A total of 23/685 (3.4%) patients had been
      hospitalized for liver disease and 5 had liver-related mortality. Eight patients
      developed cirrhosis (7 decompensated, 5 died), 5 had "cryptogenic" cirrhosis in
      which DILI might have played a role in this development. Duration of therapy
      before DILI was longer in patients with liver-related morbidity/mortality (135+/
      31 days vs. 53+/-3; p<0.0001). Autoimmune hepatitis developed in 5/23 (22%), all
      of female gender after a mean of 5.8 years. CONCLUSIONS: Development of
      clinically important liver disease after severe DILI associated with jaundice is
      rare after acute DILI. However decompensated "cryptogenic" cirrhosis developed in
      some patients with fatal outcome in which DILI might have played a role in this
      development.

PMID- 19155083
TI  - Serum retinol-binding protein 4 is inversely correlated with disease severity of
      chronic hepatitis C.
AB  - BACKGROUND/AIMS: Hepatitis C virus (HCV) infection carries a significant risk for
      development of insulin resistance (IR) and/or diabetes mellitus. Recently,
      retinol-binding protein 4 (RBP4) has been reported as a protein contributing to
      IR. This study aimed to assess the correlation between RBP4 and disease severity
      of chronic HCV infection (CHC). METHODS: Serum RBP4 was measured in 105 treatment
      nai ve CHC patients and its correlation with the homeostasis model assessment of
      insulin resistance index (HOMA-IR), liver histology, virology and metabolic
      factors was investigated. Patients were stratified into different stages of
      glucose tolerance by oral glucose tolerance test. RESULTS: There was a
      significant decreasing linear trend of RBP4 dependent on both histological
      grading (from 35.8+/-16.5 microg/mL of minimal to 19.2+/-12.5 microg/mL of
      severe, P=0.002) and staging (from 34.2+/-10.0 microg/mL of F0 to 22.2+/-11.9
      microg/mL of F3-4, P=0.02) progression, whilst a significant increment of HOMA-IR
      was found. Multivariate regression analysis showed BMI (1.1, 95% CI 0.44 ~ 1.77,
      P=0.001), HDL-C (-0.40, 95% CI -0.73 ~ -0.06, P=0.02), and LDL-C (0.31, 95% CI
      0.02 ~ 0.61, P=0.04) were the significant variables for prediction of RBP4.
      CONCLUSIONS: Disease severity may limit the role of RBP4 as a predictor of IR in
      CHC.

PMID- 19155084
TI  - Targeted delivery of siRNA against hepatitis C virus by apolipoprotein A-I-bound
      cationic liposomes.
AB  - BACKGROUND/AIMS: Hepatitis C virus (HCV) is one of the major human hepatic RNA
      viruses. Recently, we developed a liver-specific siRNA delivery technology using
      DTC-Apo composed of cationic liposomes (DTC) and apolipoprotein A-I (apo A-I).
      Here, we investigated whether DTC-Apo nanoparticles can systemically deliver
      siRNA into mouse hepatocytes expressing HCV proteins and inhibit their expression
      efficiently. METHODS: A transient HCV model was constructed by hydrodynamic
      injection of plasmid DNA expressing viral structural proteins under hepatic
      control region and alpha1-antitrypsin promoter elements. Using this model, DTC
      Apo containing HCV-core-specific siRNA was intravenously injected to assess
      antiviral activity as well as the duration of silencing. RESULTS: Post
      administration of DTC-Apo/HCV-specific siRNA at a dose of 2mg siRNA/kg inhibited
      viral gene expression by 65-75% in the liver on day 2. Improved activity (95%
      knockdown on day 2) without immunotoxicity was obtained by 2'-OMe-modification at
      two U sequences on its sense strand. Notably, the gene silencing effect of the
      modified siRNA was still maintained at day 6, while the unmodified one lost RNAi
      activity after day 4. CONCLUSIONS: Our results suggest that DTC-Apo liposome is a
      highly potential delivery vehicle to transfer therapeutic siRNA especially
      targeting HCV to the liver.

PMID- 19155085
TI  - The Aurora kinase inhibitor VE-465 has anticancer effects in pre-clinical studies
      of human hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common
      malignancies worldwide and novel therapies are urgently needed. Recently,
      aberrant expression of Aurora kinases has been reported in various human cancers
      including HCC. We sought to investigate the potential of a potent and selective
      Aurora kinase inhibitor, VE-465, for targeted therapy of HCC. METHODS:
      Cytotoxicity effects of VE-465 were tested in Huh-7 and HepG2 cell lines.
      Inhibition of Aurora kinase activity was demonstrated by Western blotting and
      immunofluorescence staining. Mitotic perturbation was visualized by confocal
      microscopy. Cell cycle profiles and apoptosis were assessed by flow cytometry. In
      vivo efficacy was determined in nude mice with human HCC xenografts. RESULTS: We
      demonstrated that VE-465 induced proliferation blockade, histone H3 (Ser10)
      dephosphorylation, mitotic disturbance, endoreduplication, and apoptosis in Huh-7
      and HepG2 cells. We also found that VE-465 suppressed Aurora kinase activity,
      prevented tumor growth, and induced apoptosis in a Huh-7 xenograft model.
      CONCLUSIONS: These findings show that VE-465 has potent anticancer effects in
      human HCC. Inhibitors of Aurora kinases may deserve further exploration as
      molecular targeted agents against HCC.

PMID- 19155086
TI  - Liver biopsy findings from healthy potential living liver donors: reasons for
      disqualification, silent diseases and correlation with liver injury tests.
AB  - BACKGROUND/AIMS: Liver biopsies detect silent donor disease in potential living
      liver donors and provide material for studies of subclinical non-alcoholic fatty
      liver disease (NAFLD). Our primary goal was to determine the contribution of
      biopsy findings to potential donor evaluation. Factors contributing to pre
      clinical NAFLD and correlations between liver injury tests and histopathology
      have been also determined. METHODS: Patient records, laboratory tests and results
      of the histopathologic examination and diagnoses of 284 patients from 2001 to
      2005 were retrospectively extracted from the EDIT database. Hepatic histology was
      correlated with liver injury tests and with general demographic characteristics
      in an otherwise normal healthy population. RESULTS: A minority (n=119; 42%) of
      biopsies from this population of 143 males/141 females (average age=36.8years;
      mean BMI=26.6) were completely normal. The remainder showed steatosis (n=107;
      37%), steatohepatitis (n=44; 15%), or unexplained low-grade/early stage chronic
      hepatitis, primary biliary cirrhosis, or nodular regenerative hyperplasia (n=16;
      6%). Biopsy findings disqualified 29/56 donors. Independent risk factors for
      NAFLD by multivariate modeling, which differed by sex, included: BMI (p=0.0001),
      age (p=0.003), iron (p=0.01), and ALT (p=0.004). CONCLUSIONS: Liver biopsies
      provide valuable information about otherwise undetectable liver disease in
      potential liver donors. Obesity, age and iron, which are influenced by sex,
      contribute to NAFLD pathogenesis. Blood tests other than standard liver profiles
      are needed to detect early NAFLD.

PMID- 19155087
TI  - Prevention of steatohepatitis by pioglitazone: implication of adiponectin
      dependent inhibition of SREBP-1c and inflammation.
AB  - BACKGROUND/AIMS: Peroxisome proliferator-activated receptor gamma (PPARgamma)
      agonist drugs, like pioglitazone (PGZ), are proposed as treatments for
      steatohepatitis. Their mechanisms of action remain ill-clarified. METHODS: To
      test the hypothesis that PGZ improves steatohepatitis through adiponectin
      dependent stimulation of AMPK and/or PPARalpha, mice lacking adiponectin (Adipo(
      /-)) or the AMPKalpha1 catalytic subunit (AMPKalpha1(-/-)) or wild-type (Wt) mice
      were fed the methionine and choline deficient (MCD) diet, supplemented or not
      with PGZ. RESULTS: In Wt mice, PGZ increased circulating levels of adiponectin
      and reduced the severity of MCD-induced steatohepatitis but there was no evidence
      of activation of AMPK or PPARalpha and their downstream targets. By contrast, PGZ
      completely repressed nuclear translocation of SREBP-1c, a key transcription
      factor for de novo lipogenesis. This effect was lacking in Adipo(-/-) mice in
      which PGZ failed to prevent steatohepatitis. Surprisingly, AMPKalpha1(-/-) mice
      were resistant to MCD-induced steatohepatitis, a status also associated with
      repression of SREBP-1c. CONCLUSIONS: The preventive effect of PGZ on MCD-induced
      steatohepatitis depends on adiponectin upregulation but apparently does not
      involve AMPK or PPARalpha activation. The inhibition of SREBP-1c and dependent
      repression of lipogenesis are likely to participate in this effect. The
      mechanisms by which PGZ and adiponectin control SREBP-1c and inflammation remain
      to be elucidated.

PMID- 19155088
TI  - LIM and SH3 protein 1 (Lasp1) is a novel p53 transcriptional target involved in
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the leading causes of
      cancer-related death worldwide with poor prognosis associated with tumor invasion
      and metastasis. The tumor suppressor p53 plays critical roles in tumor
      development, but there is increasing evidence for its involvement in tumor
      metastasis with the underlying mechanisms largely unexplored. METHODS: Using
      combinatorial analysis of a p53 binding database with HCC microarray expression
      profile, we identified a novel metastasis-related gene Lasp1 as a potential p53
      target. RESULTS: In this study, we demonstrate that Lasp1 is indeed a bona fide
      p53 target by validating the functional repression effect of p53 on Lasp1 via a
      p53 response element. Transient transfection of wild-type p53 but not the mutant
      form suppressed Lasp1 in Hep3B (p53-/-) cells, while p53 siRNA up-regulated its
      expression in HepG2 (p53+/+) cells. p53 mutations at key residues involved in DNA
      binding abrogates the p53-mediated suppression of Lasp1 expression. In addition,
      Lasp1 regulates HCC cell growth as well as cell migration and invasion ability.
      CONCLUSIONS: p53 transcriptionally represses Lasp1, which is a partner protein in
      affecting HCC cell motility. This suggests that p53 may play a role in
      influencing tumor metastasis through Lasp1.

PMID- 19155089
TI  - Regulation of hepatitis C virus replication by microRNAs.

PMID- 19155090
TI  - Differentiation between malignancy and inflammation in pulmonary ground-glass
      nodules: The feasibility of integrated (18)F-FDG PET/CT.
AB  - BACKGROUND: (18)F-FDG PET/CT has been used to differentiate malignant solid lung
      nodules from benign nodules. We assess the feasibility of integrated (18)F-FDG
      PET/CT for the differentiation of malignancy from inflammation manifested as
      ground-glass nodules (GGNs) on chest CT. METHODS: A total of 68 GGNs in 45
      patients (M:F=24:21; mean age, 61) fulfilled the following criteria: (a) nodules
      composed of >/=50% ground-glass opacity, (b) patients who underwent integrated
      PET/CT within 1 week following dedicated chest CT, (c) definitive diagnosis
      determined by pathological specimen or at least 9 months of follow-up, and (d)
      lesions >/=10mm in diameter. 36 malignant GGNs were pathologically proved as
      adenocarcinoma (n=20), bronchioloalveolar carcinoma (n=11), low-grade lymphoma
      (n=3), metastatic mucinous adenocarcinoma (n=1) and unknown low-grade malignancy
      (n=1). 32 inflammatory GGNs were confirmed as pneumonic infiltration as they had
      disappeared on follow-up CT and were associated with compatible clinical features
      (n=26) or as chronic inflammation with fibrosis by VATS biopsy (n=6). Using CT
      density histogram analysis, 14 were classified as pure GGNs and 54 as part-solid
      nodules. Integrated PET/CT was evaluated by measuring the maximum standardized
      uptake value (SUV) at the region of interest located at each lesion. The Mann
      Whitney U test was performed to compare the SUV of malignancy and inflammation.
      The optimal cut-off value of SUV to differentiate malignancy from inflammation
      was determined using a receiver operating characteristic-based positive test.
      Sensitivity, specificity, accuracy, and positive predictive values (PPV) and
      negative predictive values (NPV) were calculated at the level of the optimal cut
      off value. SUV showing 100% PPV for inflammatory GGNs was evaluated. RESULTS: In
      part-solid nodules, the maximum SUV was significantly higher in inflammation
      (2.00+/-1.18; range, 0.48-5.60) than in malignancy (1.26+/-0.71; range, 0.32-2.6)
      (P=0.018). On the other hand, in pure GGNs, the maximum SUV of malignancy (0.64+/
      0.19; range, 0.43-0.96) and inflammation (0.74+/-0.28; range, 0.32-1.00) showed
      no difference (P=0.37). Using the optimal cut-off value of SUV as 1.2 (P=0.01)
      sensitivity, specificity, accuracy, PPV and NPV in part-solid nodules were 62.1%,
      80.0%, 70.4%, 78.3% and 64.5%, respectively. Six part-solid nodules, which showed
      a maximum SUV of higher than 2.6, were all inflammations. CONCLUSION: The part
      solid nodules with positive FDG-PET could be inflammatory nodules rather than
      malignant nodules. This is a quite paradoxical result when considering the basic
      knowledge that malignant pulmonary nodules have higher glucose metabolism.

PMID- 19155091
TI  - Quantification of biodegradation for o-xylene and naphthalene using first order
      decay models, Michaelis-Menten kinetics and stable carbon isotopes.
AB  - At a former wood preservation plant severely contaminated with coal tar oil, in
      situ bulk attenuation and biodegradation rate constants for several monoaromatic
      (BTEX) and polyaromatic hydrocarbons (PAH) were determined using (1) classical
      first order decay models, (2) Michaelis-Menten degradation kinetics (MM), and (3)
      stable carbon isotopes, for o-xylene and naphthalene. The first order bulk
      attenuation rate constant for o-xylene was calculated to be 0.0025 d(-1) and a
      novel stable isotope-based first order model, which also accounted for the
      respective redox conditions, resulted in a slightly smaller biodegradation rate
      constant of 0.0019 d(-1). Based on MM-kinetics, the o-xylene concentration
      decreased with a maximum rate of k(max)=0.1 microg/L/d. The bulk attenuation rate
      constant of naphthalene retrieved from the classical first order decay model was
      0.0038 d(-1). The stable isotope-based biodegradation rate constant of 0.0027 d(
      1) was smaller in the reduced zone, while residual naphthalene in the oxic part
      of the plume further downgradient was degraded at a higher rate of 0.0038 d(-1).
      With MM-kinetics a maximum degradation rate of k(max)=12 microg/L/d was
      determined. Although best fits were obtained by MM-kinetics, we consider the
      carbon stable isotope-based approach more appropriate as it is specific for
      biodegradation (not overall attenuation) and at the same time accounts for the
      dominant electron-accepting process. For o-xylene a field based isotope
      enrichment factor epsilon(field) of -1.4 could be determined using the Rayleigh
      model, which closely matched values from laboratory studies of o-xylene
      degradation under sulfate-reducing conditions.

PMID- 19155092
TI  - Dynamics of gut mucosal and systemic Th1/Th2 cytokine responses in interferon
      gamma and interleukin-12p40 knock out mice during primary and challenge
      Cryptosporidium parvum infection.
AB  - Cryptosporidium parvum is an intracellular parasite causing enteritis which can
      become life-threatening in the immunocompromised host. CD4+ T cells and
      interferon (IFN)-gamma play dominant roles in host immune response to infection.
      However, effector mechanisms that are responsible for recovery from infection are
      poorly understood. In the present study we analyzed mice deficient in IFN-gamma
      or interleukin (IL)-12 in parallel to C57BL/6 wild type mice as models for murine
      cryptosporidiosis. Our results identified IFN-gamma as the key cytokine in the
      innate as well as adaptive immunity during primary and also challenge C. parvum
      infection. Furthermore, both Th1 and Th2 cytokines appear to contribute to the
      resolution of a primary infection, the former being dominant over the latter.
      Dramatic changes in the expression of cytokine genes were seen in the ileum (the
      site of infection) but not in the mesenteric lymph nodes and spleen. During re
      challenge, a significant increase of IFN-gamma was recorded in IL-12 deficient
      mice (IL-12KO). Additionally, we present data suggesting a contribution of IL-18
      in resistance of C. parvum infection even in the absence of IFN-gamma. Anti-IL-18
      antibody treatment led to increased susceptibility to infection in both strains
      of immunodeficient mice. Besides its function in inducing IFN-gamma in IL-12
      knock out mice, IL-18 appears to be involved in the regulation of the Th1/Th2
      responses in C. parvum. Neutralization resulted in a cytokine imbalance with up
      regulation of systemic (spleen) Th2 cytokine genes, notably IL-4 and IL-13. These
      data demonstrate that susceptibility or resistance to C. parvum infection depends
      on a delicate balance between the production of Th1 cytokines, needed to control
      parasite growth, and Th2 cytokines, to limit pathology.

PMID- 19155093
TI  - Molecular and functional characterization of a cDNA encoding 4-hydroxy-3
      methylbut-2-enyl diphosphate reductase from Dunaliella salina.
AB  - In green algae, the final step of the plastidial methylerythritol phosphate (MEP)
      pathway is catalyzed by 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR;
      EC: 1.17.1.2), an enzyme proposed to play a key role in the regulation of
      isoprenoid biosynthesis. Here we report the isolation and functional
      characterization of a 1959-bp Dunaliella salina HDR (DsHDR) cDNA encoding a
      deduced polypeptide of 474 amino acid residues. Phylogenetic analysis implied a
      cyanobacterial origin for plant and algal HDR genes. Steady-state DsHDR
      transcript levels were higher in D. salina cells submitted to nutritional
      depletion, high salt and/or high light, suggesting that DsHDR may respond to the
      same environmental cues as genes involved in carotenoid biosynthesis.

PMID- 19155094
TI  - The effect of multiple cycles of contamination, detergent washing, and
      disinfection on the development of biofilm in endoscope tubing.
AB  - BACKGROUND: Patient soil and bacterial biofilm in patient-ready endoscope
      channels can adversely impact the efficacy of detergent and disinfectant, thereby
      increasing the risk of nosocomial infection. Biofilm bacteria are firmly attached
      to one another and to the substrate by exopolysaccharide, making them difficult
      to remove. We analyzed the effect of 20 wash/contamination cycles on biofilm
      formation. MATERIALS: Pseudomonas aeruginosa biofilm-covered endoscope tubing was
      soaked in water (control), an enzymatic cleaner, or a nonenzymatic cleaner
      (Matrix) for 10 minutes and decontaminated in a washer-disinfector machine. Media
      containing P aeruginosa was then recycled to simulate contamination in clinical
      practice. RESULTS: SEM analysis showed that loosely attached biofilm was removed
      under the high flow rates in the washer-disinfector. The control tubing remained
      100% covered with biofilm, which became thicker with increased recontamination
      cycles. Washing in the enzymatic detergent retarded the redevelopment of biofilm.
      The nonenzymatic cleaner (Matrix) continued to remove more biofilm with an
      increasing number of wash/contamination cycles. At the 20th cycle, 90% of the
      tubing was biofilm-free. CONCLUSION: Washing endoscopes under high flow rates
      with some detergents removes established biofilm and retards biofilm generation,
      emphasizing the importance of cleaning before disinfection. Continued research
      into the physicochemical mechanisms of biofilm adherence and removal is needed to
      optimize detergents.

PMID- 19155095
TI  - Promoting hand hygiene and prudent use of antimicrobials in long-term care
      facilities.
AB  - A multidisciplinary team visited all long-term care facilities (n = 123) for
      elderly persons in the Central Finland health care district (population, 265,000)
      during 2004-2005. Use of alcohol-based hand rubs and ongoing systematic
      antimicrobials were assessed. Thereafter, regional guidelines for prudent use of
      antimicrobials were published. One year after the visits, a significant increase
      in the mean amount of alcohol-based hand rubs used was detected while usage of
      antimicrobials for the prevention of urinary tract reinfections had decreased.

PMID- 19155097
TI  - Methicillin resistance of airborne coagulase-negative staphylococci in homes of
      persons having contact with a hospital environment.
AB  - BACKGROUND: The persons having contact with a hospital environment (hospital
      personnel workers and discharged patients) are highly exposed to colonization
      with multidrug-resistant bacteria. The aim of this study was to evaluate the
      airborne Staphylococcus genus features in homes in which inhabitants have had
      contact with the hospital environment. METHODS: Airborne bacteria were collected
      using a 6-stage Anderson impactor. The Staphylococcus species composition and
      resistance to methicillin, and other antimicrobial agents among 3 coagulase
      negative staphylococci (CNS) species (S cohnii spp cohnii, S epidermidis, S
      hominis), were determined. Antibiotic resistance of isolates was tested using the
      agar screen method with methicillin, the polymerase chain reaction technique to
      detect the mecA gene, and the disk diffusion method. RESULTS: A higher prevalence
      of methicillin-resistant (MR) strains among the species isolated (40% of S
      epidermidis, 40% of S hominis, and 60% of S cohnii spp cohnii) was found in homes
      of persons who had contact with a hospital environment compared with the
      reference homes (only 12% of S hominis). The mecA gene was revealed in all MR S
      epidermidis strains and in some MR S hominis (50%) and S cohnii spp cohnii (33%)
      strains. All isolated MR CNS strains were susceptible to vancomycin, rifampicin,
      and linezolid. CONCLUSION: High numbers of airborne multidrug-resistant MR CNS in
      the homes of persons having contact with a hospital environment indicates that
      such inhabitants pose a risk of intrafamilial spreading of MR strains via air.

PMID- 19155096
TI  - Extended-spectrum beta-lactamase-producing pathogens in a children's hospital: a
      5-year experience.
AB  - BACKGROUND: Pediatric infection with bacteria producing extended-spectrum beta
      lactamases (ESBLs) has not been well described. We sought to determine the
      proportion of isolates producing ESBLs and the incidence of infection or
      colonization with these organisms in our tertiary care pediatric facility over 5
      years. In addition, we sought to evaluate the characteristics of children
      affected. METHODS: We identified all Escherichia coli or Klebsiella spp cultured
      from children younger than 18 years of age at our facility between January 2003
      and December 2007. Medical records were reviewed for affected children. RESULTS:
      Of 2697 E coli, K pneumoniae, and K oxytoca cultured, 26 ESBL producers were
      isolated from 16 children. Rates of ESBL production among cultured isolates
      significantly increased, from 0.53% in the first half of the study period to 1.4%
      in the second. Incidence of a primary ESBL infection also increased
      significantly, from 0.14/10,000 patient encounters to 0.31/10,000. The majority
      of children infected or colonized with ESBL-producing organisms were those with
      chronic medical conditions, frequent hospitalizations, or a history of recurrent
      infection. However, 4 affected children were less than 5 months old and evaluated
      in an outpatient setting. CONCLUSION: Rates and incidence of ESBL infection
      increased over the study period. Whereas most patients belonged to traditional
      risk groups for antibiotic-resistant infection, infants in the ambulatory setting
      were also affected, an at-risk population not previously described.

PMID- 19155098
TI  - Hospitalizations for nosocomial rotavirus gastroenteritis in a tertiary pediatric
      center: a 4-year prospective study.
AB  - BACKGROUND: Although rotavirus is the most common cause of gastroenteritis
      worldwide, data regarding nosocomial rotavirus gastroenteritis (NRVGE) are
      limited. Our objectives were to study the rates, seasonality, epidemiology, and
      clinical features of NRVGE. METHODS: This was a 4-year prospective study.
      RESULTS: NRVGE occurred in 1% of all admissions (356/35,833), 0.8% of all
      hospitalization days (1164/145,595) and 0.24 cases per 100 hospitalization days.
      Rates of NRVGE were age-dependent, occurring in 1.8%, 1.5%, 0.3%, and 0.1% of the
      admissions of children age < or = 1, > 1 to 2, > 2 to 5, and > 5 years,
      respectively (P < .001). Of the children age > 5 years, 90% received
      immunosuppressive treatment or had significant underlying diseases. The number of
      NRVGE cases was highest in winter months, but it occurred throughout the year,
      and its percentage of all hospitalizations for rotavirus gastroenteritis was
      highest in the summer months. NRVGE occurred after a median hospitalization of 6
      days, required a median hospital stay of 3 days, and warranted treatment with
      intravenous fluids in 67% of cases. CONCLUSION: NRVGE is a significant health
      burden, especially in children age < or = 2 years, although it also can affect
      children age > 5 years with significant underlying disturbances. Vaccine
      prevention of rotavirus gastroenteritis also could reduce NRVGE and should be
      considered in cost-effectiveness analyses.

PMID- 19155099
TI  - Evidence of hepatitis C virus-specific interferon gamma-positive T cells in
      health care workers in an infectious disease department.
AB  - BACKGROUND: Few studies are available on possible hepatitis C virus (HCV)
      specific T-cell immune response in health care workers (HCWs) involved in the
      care of patients with HCV infection. We aimed to investigate whether a HCV
      specific interferon (IFN)-gamma T-cell response, known to be involved in
      infection resolution, was present in those HCWs involved in the management of
      patients with persistent HCV infection. METHODS: Our study involved 30 subjects,
      classified as group A (20 consecutive patients, 16 males and 4 females, with
      histologically proven chronic hepatitis), or group B (10 HCWs, 7 males and 3
      females, with at least 7 years of health care experience and HCV-RNA and anti-HCV
      negative). As a control group, we used 10 blood samples from healthy donors at a
      blood donor center (group C). HCV-RNA was measured by real-time polymerase chain
      reaction. Blood samples (at least 35 mL) were collected from all group A and
      group B subjects in our hospital. Specific IFN-gamma was stimulated with HCV pool
      peptides (core, 2 microg/mL), with influenza Mp peptides used as a positive
      control. RESULTS: Levels of HCV-specific IFN-gamma-positive cells were higher in
      the HCWs (group B) compared with the infected patients (group A) and healthy
      blood donors (group C) (Mann-Whitney U test, P < .001). CONCLUSION: A clinically
      silent persistent exposure to HCV, through some as-yet undetermined mechanism,
      may induce a virus-specific IFN-gamma-producing CD8(+) T-cell response in healthy
      aviremic HCWs. This finding suggests that possible unapparent parenteral routes
      may stimulate host defenses with no evidence of hepatitis.

PMID- 19155100
TI  - Efficacy of novel antimicrobial gloves impregnated with antiseptic dyes in
      preventing the adherence of multidrug-resistant nosocomial pathogens.
AB  - BACKGROUND: Contaminated gloves are a major source of transmission of bacteria in
      the hospital and food industry. We investigated the efficacy of gloves
      impregnated with a combination of antiseptics consisting of brilliant green dye
      and chlorhexidine (Gardine). METHODS: Gardine-coated and uncoated 1-cm(2)
      segments of latex examination and nitrile examination gloves (Spontex, Columbia,
      TN) were exposed to 1.5 x 10(8) colony-forming units (CFU)/mL methicillin
      resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci,
      multidrug resistant (MDR) Escherichia coli, MDR-Acinetobacter baumannii, or
      Candida albicans as indicated by our brief exposure method. At least 3 glove
      segments were tested in each group, and growth was scored as mean CFU/cm(2).
      Segments were dried for various time periods (30 seconds, 10 minutes, 30 minutes,
      and 1 hour) and streaked face down on agar plates. Plates were incubated
      overnight at 37 degrees C, and growth was quantitated. RESULTS: Gardine-coated
      latex and nitrile gloves showed significant reduction, an average of 6 logs and 5
      logs, respectively, within 30 seconds or 10 minutes when tested against MRSA,
      vancomycin-resistant enterococci, MDR-E coli, MDR-Acientobacter, and C albicans.
      Complete kill, 8-log reduction, was seen within 30 seconds for MRSA and E coli in
      both Gardine-coated latex and nitrile gloves. CONCLUSION: Gloves impregnated with
      Gardine antiseptic dye were highly efficacious in preventing contamination of
      nosocomial-resistant pathogens on the outer surface of glove and may be useful in
      the food industry or clinical setting.

PMID- 19155102
TI  - No association of lipase C polymorphisms with Alzheimer's disease.
AB  - Hepatic lipase, also known as hepatic triglyceride lipase (LIPC), much like the
      major genetic risk factor for Alzheimer's disease (AD), apolipoprotein E (APOE),
      is associated with altered lipid metabolism. As such this link makes LIPC a
      potential functional candidate for AD risk. Previously, three single nucleotide
      polymorphisms (SNPs) have been investigated in AD with a lack of association
      reported. To rule out a possible contribution of other variants in LIPC, located
      at 15q21-q23, we used a detailed fine mapping approach in a German case-control
      sample. Genotyping of 25 single nucleotide polymorphisms covering the complete
      LIPC gene and haplotypic analysis revealed no association with AD. Thus, we
      conclude that LIPC can be excluded as a major functional candidate gene
      conferring risk to AD.

PMID- 19155101
TI  - Pronounced microgliosis and neurodegeneration in aged rats after tau gene
      transfer.
AB  - Microtubule-associated protein tau gene transfer to the substantia nigra of rats
      using the adeno-associated virus (AAV) vector previously led to neuropathology
      and neurodegeneration in young rats. In this study, we compared equal tau gene
      transfer in either 3 or 20-month-old rats, in order to test the hypothesis that
      late middle-aged rats are more susceptible to neurodegeneration. Two intervals
      and two vector doses of the tau vector probed for age-related differences in the
      initial sensitivity to low-level tau expression. Gene transfer efficiency was
      similar for both ages, but the tau vector caused more dopaminergic cell loss and
      a greater behavioral deficit in aged rats at specific doses and time points. Tau
      gene transfer caused microgliosis relative to the control vector, and to a
      greater extent in aged rats. The maximal microglial response occurred at 2 weeks
      preceding the peak dopaminergic cell loss by 8 weeks. The cellular and behavioral
      outcomes were more severe in the aged rats, validating the model for studies of
      age-related diseases.

PMID- 19155103
TI  - DNA-targeting pyrroloquinoline-linked butenone and chalcones: synthesis and
      biological evaluation.
AB  - A series of conjugates of alpha,beta-unsaturated ketone systems, phenyl-butenone
      and diaryl-propenones (chalcones), with the tricyclic planar pyrroloquinoline
      nucleus were synthesised and evaluated for their anticancer properties. The aim
      was to target DNA by butenone and chalcones, and determine the occurrence of
      interactions with the macromolecule or related functional enzymes. The ability to
      inhibit cell growth was assayed on three human tumor cell lines, and the capacity
      to form molecular complexes with DNA was studied by linear flow dichroism (LD).
      The effect on the activity of the nuclear enzyme DNA topoisomerase II was also
      investigated. A noticeable cytotoxic effect was observed for all pyrroloquinoline
      conjugated compounds 5 and 7a-c, particularly against human melanoma cell line
      JR8 (IC(50) 1.2-3.3 microM); the unconjugated chalcones (8a-c) and butenone had a
      lower or no effect at the tested concentrations. LD experiments confirmed the
      pyrroloquinoline nucleus as an efficacious carrier for intercalative complexation
      with DNA. The ability of pyrroloquinoline derivatives to intercalate between base
      pairs appears to inhibit the relaxation of supercoiled DNA by topoisomerase II,
      while they induce no significant DNA cleavage. Since the concentrations
      inhibiting the enzyme appear relatively high with respect to cytotoxicity, the
      effective intercalation could affect the activity of more DNA processing enzymes
      and these overall nuclear effects may induce cell death.

PMID- 19155104
TI  - Synthesis, characterization, DNA cleavage and in vitro antimicrobial studies of
      La(III), Th(IV) and VO(IV) complexes with Schiff bases of coumarin derivatives.
AB  - A series of La(III), Th(IV) and VO(IV) complexes have been synthesized with
      Schiff bases derived from 8-formyl-7-hydroxy-4-methylcoumarin and o
      phenylenediamine/ethylenediamine. The structure of the complexes has been
      proposed in the light of analytical, spectral (IR, UV-vis, ESR and FAB-mass),
      Magnetic and thermal studies. The complexes are soluble in DMF and DMSO. The
      measured molar conductance values indicate that, the complexes are non
      electrolytes in nature. The redox behavior of the complexes was investigated by
      electrochemical method using cyclic voltammetry. The Schiff bases and their
      complexes have been screened for their antibacterial (Escherichia coli,
      Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi) and
      antifungal activities (Aspergillus niger, Aspergillus flavus and cladosporium) by
      Minimum Inhibitory Concentration method. The DNA cleavage activity of La(III) and
      VO(IV) metal complexes is studied by agarose gel electrophoresis method.

PMID- 19155105
TI  - Current thinking in temporomandibular joint management.
AB  - The management of temporomandibular joint (TMJ) disorders in secondary care has
      progressed through the 1990s from a condition dealt with by generalists to one
      with an increasing number of surgeons with a subspecialist interest. Within this
      latter group there is a subgroup of those with a specific training towards joint
      replacement surgery. Increasingly patients who previously had surgery for pain
      are being managed with non-surgical options. Alternative pain management regimens
      with the introduction of botulinum toxin as well as tricyclic medication have
      reduced the need for any invasive management. The surgical management of the TMJ
      has been revolutionised by the introduction of arthroscopy in the late 1970s. The
      use of arthroscopy and arthrocentesis has lead to a reduction in indications for
      open joint surgery. There is no longer a perceived need to correct internal
      derangement with disc repositioning surgery. The primary management of acute
      restriction of opening and joint pain is now with arthrocentesis and arthroscopy.
      Degenerative and ankylotic conditions of the joint can be safely treated by the
      use of alloplastic joint replacement, which has less morbidity and more
      predictable outcomes than costochondral grafting, with the latter still the
      method of choice in children. The revolution continues with the introduction of
      national guidelines and databases supported by BAOMS.

PMID- 19155106
TI  - Free microvascular transfer of segmental corticocancellous femur for
      reconstruction of the alveolar ridge.

PMID- 19155107
TI  - Postoperative monitoring of microsurgical free-tissue transfers for head and neck
      reconstruction: a systematic review of current techniques--part II. Invasive
      techniques.
AB  - A systematic review of the literature relating to methods of monitoring viability
      of microvascular free-tissue transfers in the head and neck region was conducted.
      The aim of this review is to identify the best method of monitoring that would
      allow timely salvage of potentially failing free flaps. An analysis and
      description of the various studied techniques is also given. In this second part,
      invasive modalities are covered.

PMID- 19155108
TI  - Osteochondroma of the mandibular coronoid process: a rare cause of limited mouth
      opening.

PMID- 19155109
TI  - Modelling the long-term soil response to atmospheric deposition at intensively
      monitored forest plots in Europe.
AB  - The dynamic soil chemistry model SMART was applied to 121 intensive forest
      monitoring plots (mainly located in western and northern Europe) for which both
      element input (deposition) and element concentrations in the soil solution were
      available. After calibration of poorly known parameters, the model accurately
      simulated soil solution concentrations for most plots as indicated by goodness-of
      fit measures, although some of the intra-annual variation especially in nitrate
      and aluminium concentrations could not be reproduced. Model evaluations of two
      emission-deposition scenarios (current legislation and maximum feasible
      reductions) for the period 1970-2030 show a strong reduction in sulphate
      concentrations between 1980 and 2000 in the soil due to the high reductions in
      sulphur emissions. However, current legislation hardly reduces future nitrogen
      concentrations, whereas maximum feasible reductions reduces them by more than
      half. Maximum feasible reductions are also more effective in increasing pH and
      reducing aluminium concentrations, mostly below 'critical' values.

PMID- 19155110
TI  - Gaseous mercury emissions from unsterilized and sterilized soils: the effect of
      temperature and UV radiation.
AB  - Mercury (Hg) emissions from the soils taken from two different sites (deciduous
      and coniferous forests) in the Adirondacks were measured in outdoor and
      laboratory experiments. Some of the soil samples were irradiated to eliminate
      biological activity. The result from the outdoor measurements with different
      soils suggests the Hg emission from the soils is partly limited by fallen leaves
      covering the soils which helps maintain relatively high soil moisture and limits
      the amount of heat and solar radiation reaching the soil surface. In laboratory
      experiments exposure to UV-A (365 nm) had no significant effect on the Hg
      emissions while the Hg emissions increased dramatically during exposure to UV-B
      (302 nm) light suggesting UV-B directly reduced soil-associated Hg. Overall these
      results indicate that for these soils biotic processes have a relatively constant
      and smaller influence on the Hg emission from the soil than the more variable
      abiotic processes.

PMID- 19155111
TI  - Source term characterisation using concentration trends and geochemical
      associations of Pb and Zn in river sediments in the vicinity of a disused mine
      site: implications for contaminant metal dispersion processes.
AB  - River sediment at a disused lead-zinc mine was analysed to provide an
      understanding of the chemical nature of the source term for contaminated sediment
      exported from the site. Changes in concentration and geochemical associations of
      Pb and Zn were measured using aqua regia digestion and the BCR sequential
      extraction procedure. Sediment in the immediate vicinity of the mine was highly
      contaminated with Pb (max. c. 11,000 mg kg(-1)) and Zn (max. c. 30,000 mg kg(
      1)), but these values declined rapidly within 1 km of the mine due to dilution
      and hydraulic sorting. Lead fractionation changed from being predominantly in the
      reducible fraction to being in the acetic acid-extractable fraction, whereas Zn
      was predominantly in the residual fraction. This material is transported as fine
      sediment in the river system.

PMID- 19155112
TI  - Building social capital in post-conflict communities: evidence from Nicaragua.
AB  - Studies of social capital have focused on the static relationship between social
      capital and health, governance and economic conditions. This study is a first
      attempt to evaluate interventions designed to improve the levels of social
      capital in post-conflict communities in Nicaragua and to relate those increases
      to health and governance issues. The two-year study involved a baseline household
      survey of approximately 200 households in three communities in Nicaragua, the
      implementation of systematic interventions designed to increase social capital in
      two of the locales (with one control group), and a second household survey
      administered two years after the baseline survey. We found that systematic
      interventions promoting management and leadership development were effective in
      improving some aspects of social capital, in particular the cognitive attitudes
      of trust in the communities. Interventions were also linked to higher levels of
      civic participation in governance processes. As in other empirical studies, we
      also found that higher levels of social capital were significantly associated
      with some positive health behaviors. The behavioral/structural components of
      social capital (including participation in groups and social networks) were
      associated with more desirable individual health behaviors such as the use of
      modern medicine to treat children's respiratory illnesses. Attitudinal components
      of social capital were positively linked to community health behaviors such as
      working on community sanitation campaigns. The findings presented here should be
      of interest to policy makers interested in health policy and social capital, as
      well as those working in conflict-ridden communities in the developing world.

PMID- 19155113
TI  - A double-edged sword? Health research and research governance in UK primary care.
AB  - Contemporary health research is becoming increasingly formalised, regulated and
      institutionalised. In the UK, this has manifested itself in the development of a
      framework for 'governing' health research. The framework is often presented as a
      neutral decision-making tool guiding elements of research (such as ethical and
      peer review) through formal governance processes and approval procedures. We
      locate the framework as emerging in the wider context of the growth of
      'guidelines' in healthcare that raises questions about the extent to which formal
      rationality has taken hold on knowledge production and what this means for health
      research. We therefore explore if and how the framework prioritises particular
      approaches to the production of knowledge and the tensions that emerge between
      managerial requirements and the work of researchers. We employed qualitative
      telephone interviews to access the accounts of both researchers and
      administrators across a range of primary healthcare settings in England and to
      capture a range of experiences and levels of involvement in research and
      governance. Our analysis revealed the double-edged nature of research governance:
      on the one hand, the framework provided a valuable aid to decision-making and the
      formalisation of tacit knowledge about 'good research practice'; on the other,
      consequent managerial processes engaged researchers in a series of low-level
      activities and privileged particular ways of viewing the world. Our findings add
      to existing knowledge by moving beyond documenting concerns over research
      governance and show how the reduction of research governance according to a
      'common' set of principles and procedures facilitates the production (and
      managerial oversight) of quantitative and clinical, over qualitative and
      experiential, knowledge.

PMID- 19155114
TI  - Childhood mistreatment and adolescent and young adult depression.
AB  - In this paper, I use a nationally representative sample of adolescents from the
      United States to examine the association between childhood mistreatment (sexual
      abuse and physical abuse) and depression during adolescence and young adulthood.
      Researchers have implicated childhood mistreatment as one of the most important
      predictors of depression. An alternative mechanism linking childhood mistreatment
      with adolescent and young adult depression is community and family disadvantage
      (or other factors) that affect both outcomes. Using data from the restricted
      version of the U.S. National Longitudinal Study of Adolescent Health (Add
      Health), this paper outlines several findings of the relationship between
      mistreatment and depression as well as the gender differences in depression.
      First, I find very limited evidence that controlling for common environmental
      factors at the school or neighborhood level explain the relationship between
      mistreatment and depression. Also, I show that controlling for common family
      factors decreases the predictive power of childhood mistreatment on depression.
      Results in this paper generally support previous research that shows the link
      between childhood mistreatment and depression is most important for females, even
      within families. Finally, results suggest that the effects of child mistreatment
      on depression may increase as individuals age.

PMID- 19155115
TI  - Effects of neighborhood characteristics on the mortality of black male youth:
      evidence from Gautreaux, Chicago.
AB  - We estimate the effect of neighborhood characteristics on the mortality of poor
      black male youth in families relocated through the Gautreaux Assisted Housing
      Program, a residential mobility program implemented in Chicago, USA in 1976.
      Within our sample (N=2850), 52 post-placement deaths were observed, the majority
      of which (30) were homicides. All-cause and homicide mortality rates were
      substantially lower among those relocating to Census tracts with higher fractions
      of residents with college degrees, which suggests that relocating to more
      advantaged neighborhoods can ameliorate the mortality risks faced by this
      population. The estimated effect declines over the post-placement period, a
      result consistent with evidence that Gautreaux families routinely relocated
      following their initial placement. A causal interpretation of these findings is
      undermined somewhat by evidence of neighborhood selection, though the mortality
      effect estimate is very robust to inclusion of covariates predictive of placement
      tract characteristics. Mortality effect estimates relating to Census tract
      measures of socioeconomic deprivation other than education were weaker in
      magnitude and generally insignificant, suggesting that neighborhood levels of
      human capital more strongly affect the mortality risks faced by this population
      than racial composition or neighborhood poverty.

PMID- 19155116
TI  - EDTA or H3PO4/NaOCl dentine treatments may increase hybrid layers' resistance to
      degradation: a microtensile bond strength and confocal-micropermeability study.
AB  - OBJECTIVES: The aim of this study was to reduce hybrid layer degradation created
      with simplified dentine adhesives by using two different methods to condition the
      dentine surface. METHODS: A smear-layer was created on flat dentine surfaces from
      extracted human third molars with a 180-grit/SiC-paper. Dentine specimens were
      conditioned before bonding with the following procedures: 37% H(3)PO(4);
      H(3)PO(4)/0.5% NaOCl; 0.1M EDTA; 0.1M EDTA/0.5% NaOCl. Two etch-and-rinse
      adhesives: (Scotchbond 1XT or Optibond Solo Plus) were applied and light-cured.
      Composite build-ups were constructed. The bonded teeth were sectioned into beams,
      stored in distilled water (24h) or 12% NaOCl solution (90 min) and finally tested
      for microtensile bond strengths (microTBS). Additional dentine surfaces were
      conditioned and bonded as previously described. They were prepared for a pulpal
      micropermeability confocal microscopy study and finally observed using confocal
      microscopy. RESULTS: microTBS results revealed that both adhesives gave high bond
      strengths to acid-etched dentine before, but not after a 12% NaOCl challenge.
      Bonds made to acid-etched or EDTA-treated dentine plus dilute NaOCl, gave high
      microTBS that resisted 12% NaOCl treatment, as did EDTA-treated dentine alone. A
      confocal micropermeability investigation showed very high micropermeability
      within interfaces of the H(3)PO(4), etched specimens. The lowest
      micropermeability was observed in H(3)PO(4)+0.5% NaOCl and 0.1M EDTA groups.
      CONCLUSIONS: The use of dilute NaOCl (0.5%) after acid-etching, or the
      conditioning of dentine smear layers with 0.1M EDTA (pH 7.4) produced less porous
      resin-dentine interfaces. These dentine-conditioning procedures improve the
      resistance of the resin-dentine bond sites to chemical degradation (12% NaOCl)
      and may result in more durable resin-dentine bonds.

PMID- 19155117
TI  - Learning on a simulator does transfer to clinical practice.
AB  - AIM OF THE STUDY: Cricoid pressure is recommended during positive pressure
      ventilation CPR and during anaesthesia when there is a risk of regurgitation.
      Studies suggest that cricoid pressure is frequently applied incorrectly placing
      patients at risk of regurgitation. Simulation training has been shown to improve
      the performance of cricoid pressure on a simulator, but whether simulation
      training improves the clinical performance of cricoid pressure was unknown. The
      aim of our study was to determine if simulator training improved the clinical
      performance of cricoid pressure. METHODS: 101 medical students and nursing staff
      were recruited and randomised to receive cricoid pressure simulator training with
      or without force feedback. Subjects then applied cricoid pressure to an
      anaesthetised patient while standing on a force plate. The main outcome measure
      was the number of subjects who applied a mean force of 20-30N during their trial.
      RESULTS: Significantly more subjects (20/53, 38%) in the feedback group applied
      force in the appropriate range (20-30N) compared to the control group (9/48, 19%)
      (p=0.035, chi square test). The feedback group applied significantly higher
      forces than did the control group (p=0.029, Mann-Whitney U test). CONCLUSION:
      Simulation training with force feedback significantly improved the performance of
      cricoid pressure in the clinical setting. Simulation training should be used more
      frequently to train and maintain resuscitation skills.

PMID- 19155118
TI  - The effect of additional disulfide bonds on the stability and folding of
      ribonuclease A.
AB  - The significant contribution of disulfide bonds to the conformational stability
      of proteins is generally considered to result from an entropic destabilization of
      the unfolded state causing a faster escape of the molecules to the native state.
      However, the introduction of extra disulfide bonds into proteins as a general
      approach to protein stabilization yields rather inconsistent results. By modeling
      studies, we selected positions to introduce additional disulfide bonds into
      ribonuclease A at regions that had proven to be crucial for the initiation of the
      folding or unfolding process, respectively. However, only two out of the six
      variants proved to be more stable than unmodified ribonuclease A. The comparison
      of the thermodynamic and kinetic data disclosed a more pronounced effect on the
      unfolding reaction for all variants regardless of the position of the extra
      disulfide bond. Native-state proteolysis indicated a perturbation of the native
      state of the destabilized variants that obviously counterbalances the stability
      gain by the extra disulfide bond.

PMID- 19155119
TI  - Effect of proline on thermal inactivation, denaturation and aggregation of
      glycogen phosphorylase b from rabbit skeletal muscle.
AB  - It has been shown that the relatively low concentrations of proline (0.1 M) have
      a slight accelerating effect on thermal aggregation of glycogen phosphorylase b
      (Phb) from rabbit skeletal muscle registered by the accumulaton of the aggregated
      protein. The suppression of Phb aggregation at high proline concentrations is
      mainly due to the protective action of proline on the stage of unfolding of the
      Phb molecule. The enhancement of Phb stability in the presence of the high
      concentrations of proline was demonstrated by the data on differential scanning
      calorimetry, analytical ultracentrifugation and thermoinactivation kinetics. The
      construction of the protein aggregate size versus time plots allowed the
      acceleration of the stage of Phb aggregation in the presence of high
      concentrations of proline to be demonstrated. The obtained results are consistent
      with the predictions of the crowding theory.

PMID- 19155120
TI  - Perceived and actual wildfire danger: an economic and spatial analysis study in
      Colorado (USA).
AB  - Over the last 20 years, costs for wildfire initial attack in the U.S. have
      increased significantly. The increased cost relates to wildfire suppression
      practices, as well as the growing number of homes in the wildland urban
      interface. Requiring wildland urban interface residents to pay an annual tax for
      their wildfire risk could lower costs to the general taxpayer. Willingness-to-pay
      for wildfire prevention, in relation to both perceived and actual wildfire
      danger, was the focus of this study. Surveyed Colorado wildland urban interface
      residents were found to have a high awareness of wildfire risk and were willing
      to-pay over $400 annually to reduce this risk. Respondents' beliefs about
      wildfire frequency were comparable to the wildfire regimes of their areas' pre
      European settlement.

PMID- 19155121
TI  - A spatially explicit framework for quantifying downstream hydrologic conditions.
AB  - Continued improvements in spatial datasets and hydrological modeling algorithms
      within Geographic Information Systems (GISs) have enhanced opportunities for
      watershed analysis. With more detailed hydrology layers and watershed delineation
      techniques, we can now better represent and model landscape to water quality
      relationships. Two challenges in modeling these relationships are selecting the
      appropriate spatial scale of watersheds for the receiving stream segment, and
      handling the network or pass-through issues of connected watersheds. This paper
      addresses these two important issues for enhancing cumulative watershed
      capabilities in GIS. Our modeling framework focuses on the delineation of stream
      segment-level watershed boundaries for 1:24,000 scale hydrology, in combination
      with a topological network model. The result is a spatially explicit, vector
      based, spatially cumulative watershed modeling framework for quantifying
      watershed conditions to aid in restoration. We demonstrate the new insights
      available from this modeling framework in a cumulative mining index for the
      management of aquatic resources in a West Virginia watershed.

PMID- 19155122
TI  - Prevalence of hypospadias in Danish boys: a longitudinal study, 1977-2005.
AB  - BACKGROUND: Hypospadias is a relatively common congenital malformation. Data on
      temporal trends in prevalence of hypospadias are conflicting. It is unclear
      whether changes of maternal age distribution over time are associated with
      changes in hypospadias prevalence. OBJECTIVE: To study changes in prevalence of
      hypospadias in Denmark during a 29-yr period and to investigate whether maternal
      age was associated with the prevalence of hypospadias. DESIGN, SETTING, AND
      PARTICIPANTS: Through Denmark's National Patient Registry, covering all Danish
      hospitals, we identified all boys diagnosed with hypospadias in Denmark. From the
      Danish Medical Birth Registry, we obtained information on maternal age and on the
      annual total number of live-born boys from 1977 to 2005. MEASUREMENTS: Prevalence
      of hypospadias at birth. RESULTS AND LIMITATIONS: Among 921745 boys born alive
      from 1977 to 2005, we identified 3490 boys with hypospadias. The prevalence
      increased from 0.24% in 1977 to 0.52% in 2005, corresponding with an annual
      increase in prevalence of 2.40% (95% confidence interval: 1.94-2.86). The
      prevalence of hypospadias did not differ according to maternal age. The mean
      annual prevalence was 0.38% in sons of mothers aged <or=25 yr, 0.37% in sons of
      mothers aged 26-30 yr, 0.39% in sons of mothers aged 31-35 yr, and 0.39% in sons
      of mothers >35 yr. CONCLUSIONS: The hypospadias prevalence was increasing in
      Denmark from 1977 to 2005. Increased maternal age did not explain this trend.

PMID- 19155123
TI  - Diagnostic and prognostic molecular markers for renal cell carcinoma: a critical
      appraisal of the current state of research and clinical applicability.
AB  - CONTEXT: Earlier detection of renal cell carcinoma (RCC) and the recent expansion
      of treatment possibilities have positively influenced the outlook for patients
      with this disease. However, progression and treatment response are still not
      sufficiently predictable. Molecular markers could help to refine individual risk
      stratification and treatment planning, although they have not yet become
      clinically routine. OBJECTIVE: This review presents an overview of diagnostic and
      prognostic molecular markers for RCC and a subgrouping of these markers for
      different clinical issues. EVIDENCE ACQUISITION: Literature and recent meeting
      abstracts were searched using these terms: renal (cell) carcinoma,
      molecular/tumor markers, biopsy, blood, urine, disease progression/prognosis,
      immunohistochemistry, risk factors, and survival. Due to the resulting large
      number of articles, studies were subjectively selected according to the
      importance of a study on the field, number of investigated patients, originality,
      multivariate analyses performed, contrast with previously published data,
      actuality, and assumed clinical applicability of the described results. More then
      90% of the selected studies originated from the past 10 yr; >50% of the articles
      were written in 2006 or later. EVIDENCE SYNTHESIS: These data were predominantly
      obtained via nonrandomized, retrospective, but often controlled studies. Thereby,
      the resulting level of evidence is 2A/2B. The broad spectrum of described
      molecular markers (MMs) for RCC consists of markers already extensively studied
      in other malignancies (eg, p53), as well as MMs typically associated with
      specific RCC-altered gene functions and pathways (eg, von Hippel-Lindau [VHL]).
      The main goal of using MMs is to refine the prediction of clinical end points
      like tumor progression, treatment response, and cancer-specific and/or overall
      survival. Further, MMs might facilitate the clinical work-up of undefined renal
      masses and prove to be more convenient tools for screening and follow-up in blood
      and urine. CONCLUSIONS: Presently, there are a number of promising MMs for
      diverse clinical questions, but the available data are not yet valid enough for
      routine, clinical application. We should comply with the demand for large
      multicenter prospective investigations, stratified for RCC type and treatment
      modalities, to lift the use of molecular markers in RCC to a practical level,
      thereby providing a better consultation for our patients regarding diagnosis,
      treatment, and follow-up.

PMID- 19155124
TI  - Tetra-arsenic oxide (Tetras) enhances radiation sensitivity of solid tumors by
      anti-vascular effect.
AB  - Tetras (tetra-arsenic oxide, As(4)O(6)) is a derivative of arsenic used in Korean
      traditional medicine for the treatment of cancer, but its mechanism remains
      largely undefined. Recently, a similar arsenic derivative, diarsenic trioxide
      (As(2)O(3), ATO), has been shown to mediate anti-tumor activity, therefore
      reigniting interest in the therapeutic effect of arsenic compounds. Here we
      report that Tetras can effectively mediate an anti-vascular effect on tumors,
      leading to delay in tumor growth and increased survival. Our study demonstrates
      for the first time the potential use of Tetras as a radiation therapy enhancement
      agent for solid tumors. These findings reveal an unappreciated role of Tetras in
      cancer therapy and its potential application to radiotherapy in achieving local
      tumor control.

PMID- 19155125
TI  - Kinetic and thermodynamic uranyl (II) adsorption process into modified Na
      Magadiite and Na-Kanemite.
AB  - The compound 2-mercaptopyrimidine (MPY) was attached onto synthetic Na-Magadiite
      (M) and Na-Kanemite (K) samples by homogeneous route. The final matrices named
      M(MPY) and K(MPY) have been characterized through X-ray powder diffraction and
      scanning electron microscopy (SEM). The resulted materials were submitted to
      process of adsorption with uranyl solution at pH 2.0 and 298+/-1K. The kinetic
      parameters were analyzed by the Lagergren and Elovich models of adsorption and
      demonstrated to be good fit for all experiments. From calorimetric determinations
      the quantitative thermal effects for uranyl(II)/basic center interactions gave
      exothermic enthalpy, negative Gibbs free energy, and positive entropy. These
      thermodynamic data confirmed the energetically favorable condition of such
      interactions at the solid/liquid interface for all systems.

PMID- 19155126
TI  - Dechlorination of gamma-hexachlorocyclohexane by zero-valent metallic iron.
AB  - This study investigated the rates and pathways of gamma-hexachlorocyclohexane
      (gamma-HCH) dechlorination by granular zero-valent iron under different pH, iron
      dosage and temperature conditions. It was found that gamma-HCH was rapidly
      reduced to benzene and chlorobenzene (CB) with benzene as the major product and
      that the dechlorination likely follows three steps of dichloroelimination to
      benzene, or two steps of dichloroeliminations and one step of dehydrohalogenation
      to CB. The calculated pseudo-first-order rate of gamma-HCH degradation was 0.0125
      min(-1) at pH 6.73, 25 degrees C and 10 gL(-1) iron dosage, corresponding to 55.5
      min of half-life. It was also found that the rate of gamma-HCH dechlorination
      increases as a function of reaction temperature and zero-valent iron dosage and
      decreases as a function of solution pH. The calculated activation energy is 33.5
      kJ mol(-1) at pH 6.73, which is much lower than that of dehydrohalogenation
      facilitated by hydroxyl under basic conditions. The study suggested that zero
      valent iron could be used to effectively and efficiently transform gamma-HCH.

PMID- 19155127
TI  - Elemental composition of suspended particulate matter and sediments in the
      coastal environment of Thermaikos Bay, Greece: delineating the impact of inland
      waters and wastewaters.
AB  - An integrate study on the occurrence of major, minor and trace elements in the
      coastal environment of Thermaikos Gulf, Northern Aegean Sea, was carried out. The
      elemental composition of marine sediments and suspended particulate matter from
      Thermaikos Bay as well as the composition of suspended particles from various
      inland water (3 rivers and 4 streams) and wastewater (4 types of municipal and
      industrial origin) end up to the gulf was investigated during the period 2005
      2006. The elemental profiles and characteristics of particulate matter from the
      examined water-types were discussed. The pollution status of marine sediments was
      evaluated by employing enrichment factors and sediment quality guidelines
      (TEL/PEL, ERM/ERL). Zn, Cu, Pb, As and Ag were found to have significant
      contribution from anthropogenic sources. Sites located at the northern part of
      the bay exhibited higher pollution indices and can be considered of medium-high
      priority. Principal Component Analysis was employed to find out the factors
      affecting the composition of the sediments and suspended particulate matter and
      to elucidate similarities/dissimilarities in the elemental profiles between the
      different water-types.

PMID- 19155128
TI  - Concentration-dependence of the explosion characteristics of chlorine dioxide
      gas.
AB  - The explosion characteristics of chlorine dioxide gas have been studied for the
      first time in a cylindrical exploder with a shell capacity of 20 L. The
      experimental results have indicated that the lower concentration limit for the
      explosive decomposition of chlorine dioxide gas is 9.5% ([ClO(2)]/[air]), whereas
      there is no corresponding upper concentration limit. Under the experimental
      conditions, and within the explosion limits, the pressure of explosion increases
      with increasing concentration of chlorine dioxide gas; the maximum pressure of
      explosion relative to the initial pressure was measured as 0.024 MPa at 10%
      ClO(2) and 0.641 MPa at 90% ClO(2). The induction time (the time from the moment
      of sparking to explosion) has also been found to depend on the concentration of
      chlorine dioxide gas; thus, at 10% ClO(2) the induction time was 2195 ms, but at
      90% ClO(2) the induction time was just 8 ms. The explosion reaction mechanism of
      ClO(2) is of a degenerate chain-branching type involving the formation of a
      stable intermediate (Cl(2)O(3)), from which the chain-branching occurs. Chain
      initiation takes place at the point of ignition and termination takes place at
      the inner walls of the exploder.

PMID- 19155129
TI  - Characterization of the fly ashes from the lignite burning power plants of
      northern Greece based on their quantitative mineralogical composition.
AB  - In the present work, mineralogical analysis of fly ashes produced from the brown
      coal burning power plants of Agios Dimitrios, Kardia, Ptolemais, LIPTOL,
      Amynteon, and Achlada-Meliti (Western Macedonia, Greece) was performed, with the
      aim of characterizing the ashes on the basis of their quantitative mineral phase
      composition and asses their variability at different time periods. The fly ashes
      from the Agios Dimitrios, Kardia, and Ptolemais power plants were found to have
      nearly the same mineralogical composition, consisting mainly of feldspars, lime,
      anhydrite, quartz, calcium silicates, and high amounts of amorphous phases. The
      fly ashes from Amynteon were slightly different, having lower content of lime and
      higher content of feldspars, whilst those from LIPTOL had a relative variable
      quantitative composition. The fly ashes from the Meliti-Achlada power plant
      consisted mainly of amorphous phases (very high amounts), mullite, feldspars, and
      quartz. The mineralogical composition of the ashes produced in all the power
      plants, except from these of LIPTOL, did not fluctuate significantly over time.
      An assessment of the hydraulic (cementitious) or pozzolanic character of the
      ashes is proposed, introducing the use of triangle diagrams A-B-C, which
      represent the total fraction of the phases with hydraulic or pozzolanic (A),
      inert (B) character, and the amorphous phases (C).

PMID- 19155130
TI  - Measurement and receptor modeling of atmospheric polycyclic aromatic hydrocarbons
      in urban Kaohsiung, Taiwan.
AB  - The concentrations of 21 individual polycyclic aromatic hydrocarbons (PAHs) and
      total suspended particles (TSPs) were measured using high-volume air samplers at
      Tzuo-Yin and Hsiung-Kong sites in Kaohsiung City, Taiwan, for four seasons from
      2005 to 2006. The gaseous and particulate phases of individual PAHs were
      identified using a gas chromatograph with a flame-ionization detector (GC/FID).
      Measurements show that the concentrations of total (gas+particulate) PAHs
      generally followed the seasonal variations of the concentrations of TSP (107.2
      117.1 microg m(-3)), being the highest in winter (143.9-182.9 ng m(-3)) and
      lowest in summer (81.4-95.2 ng m(-3)) at both sites. Most PAH species were low
      weight PAHs (approximately 80.8-82.0%), followed by high-weight PAHs (10.5-14.6%)
      and medium-weight PAHs (6.5-6.8%). The fractions of gaseous PAHs decreased with
      molecular weight or ring number. The particle phase (60.2(73.5%) dominated the
      high-weight PAHs. Results of receptor model show that industrial combustions
      (49.1-63.7%) contributed most to ambient PAHs, followed by restaurant emissions
      (18.4-39.7%) and mobile sources (11.3-22.8%) at the Tzuo-Yin site. At the Hsiung
      Kong, mobile sources (49.5-63.3%) contributed most to ambient PAHs, followed by
      restaurant emissions (19.8-36.6%) and industrial combustions (13.7-27.1%). The
      differences in the results at the two sites are mainly attributed to the
      different industries at each site.

PMID- 19155131
TI  - Nickel-iron layered double hydroxide (LDH): textural properties upon hydrothermal
      treatments and application on dye sorption.
AB  - NiFeCO(3) hydrotalcites with Ni/Fe molar ratio of 3 were synthesized by co
      precipitation method at constant pH, followed by hydrothermal treatment at
      various temperatures 85-180 degrees C for 3-360h. The obtained materials were
      characterized by XRD analysis, FT-IR spectroscopy, SEM and TEM microscopy, TGA
      and BET techniques. The resulting materials were found to be similar to the
      hydrotalcite with a well-defined hexagonal morphology of crystallites. The
      hydrothermal treatment and aging time increases the platelet sizes and decreases
      the surface area. XRD analysis showed the formation of sharper and intense peaks,
      which might indicate the larger crystallites size of LDH as well as higher
      crystallinity. Furthermore, textural studies revealed influence of aging time and
      temperature on the properties of the crystalline phase. The prolonged time tends
      to form additional products, identified as NiFe(2)O(4) spinel and NiO nickel
      oxide. The effect of hydrothermal treatment temperature on the kinetics of dye
      removal has been explored. It was found that the percentage color removal
      increases with increasing hydrothermal treatment temperature up to 140 degrees C
      and aging time up to 4 days. Furthermore, the color removal decreases with
      increasing hydrothermal treatment temperature up to 140-180 degrees C and
      prolonged aging time.

PMID- 19155132
TI  - Improved phenol adsorption on carbons after mild temperature steam reactivation.
AB  - The purpose of this work is to explore steam reactivation at moderate
      temperatures of activated carbon exhausted with phenol, a highly toxic compound
      frequently present in industrial wastewater. The spent carbon was treated with
      steam at various temperatures (450, 600 and 850 degrees C) and times (from 5 to
      60 min). Promising results were obtained by applying moderate temperatures and
      times. Whereas at low temperatures the complete regeneration of the carbon is not
      accomplished, an almost quantitative desorption of the pollutant was achieved at
      600 degrees C after exposure times below 30 min, with minimal damages in the
      porous network of the carbon. Further reutilization of the regenerated carbon
      resulted in a superior performance towards phenol uptake. The regeneration
      efficiency at 850 degrees C strongly depends on the time of reactivation, with an
      enhanced phenol uptake when short treatment times are applied. Prolonged duration
      of the regeneration treatment reduced phenol adsorption capacities, due to
      overreactivation of the carbon in the steam atmosphere, and to the blockage of
      the porous carbon network.

PMID- 19155133
TI  - Post-treatment of banknote printing wastewater using polysilicate ferro-aluminum
      sulfate (PSFA).
AB  - In this paper, a new kind of inorganic polymeric flocculant (IPF)-polysilicate
      ferro-aluminum sulfate (PSFA) was adopted to treat banknote printing wastewater.
      Effects of flocculants dosage on the colour and Chemical Oxygen Demand (COD)
      removal were examined. Experiments revealed that maximal colour removal
      efficiency of 98% and COD removal efficiency of 85% could be achieved at the
      optimal dosage of 30.33 g/L. And the colour and COD removal results treated by
      the PSFA flocculant were compared with those treated by aluminum sulfate.
      Experimental results showed that the most attracting parts of PSFA as compared
      with that of Al(2)(SO(4))(3) were: (i) lower COD and colour contained effluents;
      (ii) less quantity and volume sludge; (iii) better dewatering behaviour and solid
      liquid separation flocs; (iv) providing a possibility to eliminate the high
      labour intensity plate-frame pressure procedure and replace it by ordinary
      filtration. Therefore, the using of PSFA generally offered a lower cost of
      operation and maintenance choice to treat banknote printing wastewater as
      compared to that of Al(2)(SO(4))(3).

PMID- 19155134
TI  - Basic and clinical aspects of gastrointestinal pain.
AB  - The gastrointestinal (GI) tract is a system of organs within multicellular
      animals which facilitates the ingestion, digestion, and absorption of food with
      subsequent defecation of waste. A complex arrangement of nerves and ancillary
      cells contributes to the sensorimotor apparatus required to subserve such
      essential functions that are with the exception of the extreme upper and lower
      ends of the GI tract normally subconscious. However, it also has the potential to
      provide conscious awareness of injury. Although this function can be protective,
      when dysregulated, particularly on a chronic basis, the same system can lead to
      considerable morbidity. The anatomical and molecular basis of gastrointestinal
      nociception, conditions associated with chronic unexplained visceral pain, and
      developments in treatment are presented in this review.

PMID- 19155135
TI  - Anthelmintic resistance in Swedish sheep flocks based on a comparison of the
      results from the faecal egg count reduction test and resistant allele frequencies
      of the beta-tubulin gene.
AB  - A faecal egg count reduction test (FECRT) survey was conducted during the grazing
      season 2006 and 2007 to provide an updated indication of the prevalence of
      anthelmintic resistance in sheep flocks in Sweden. A total of 1330 faecal samples
      from 90 flocks on 45 farms, with a minimum of 20 ewes each, was collected by
      local sheep veterinarians. Per treatment group, approximately 15 lambs were
      dewormed either with oral suspensions of ivermectin (Ivomec vet.) or albendazole
      (Valbazen vet.). The efficacy on each farm was investigated either in 2006 or
      2007 by faecal egg counts collected on the day of treatment and in a new sample
      from the same animals 7-10 days later. Third-stage larvae (L3) were initially
      identified morphologically from pooled cultures. These were then used as the
      source of genomic DNA template for two molecular tests. The first was a PCR-based
      test for specific identification of Haemonchus contortus, and the second was a
      Pyrosequencing assay for the analysis of benzimidazole (BZ) resistance targeting
      the P200 mutation in the parasite's beta-tubulin gene. Larval cultures indicated
      that Teladorsagia and Trichostrongylus were the predominant genera, but
      Haemonchus was diagnosed in 37% of the flocks. The PCR results revealed an almost
      100% agreement with those farms that had previously been shown to have Haemonchus
      present, even when the % prevalence was low (approximately 3%). Only two (4%) of
      the surveyed farms showed evidence of BZ-resistant worm populations, with H.
      contortus being the species implicated according to post-treatment larval culture
      results. The Pyrosequencing assay detected BZ resistant allele frequencies of
      >40% in the Haemonchus-positive farms and 100% resistant alleles in the
      clinically most resistant farms. These preliminary results suggest that the FECRT
      is less sensitive than the molecular test at detecting BZ resistance. However,
      both tests need to be interpreted carefully, bearing in mind the relative
      proportions of species present and the starting egg and/or larval counts.
      Parasitological diagnosis of "clinical" resistance was also found against
      ivermectin in two flocks. However, both the pre-treatment FECs and the reductions
      in these were low, and only three lambs that had between 100 and 450 EPG after
      treatment were involved.

PMID- 19155136
TI  - Giardia and other intestinal parasites in different dog populations in Northern
      Belgium.
AB  - The objectives of this study were to obtain data on the prevalence of intestinal
      parasites in different dog populations in northern Belgium, to estimate the
      zoonotic risk associated with these infections and to identify potential risk
      factors. Between 2004 and 2007 a total of 1159 faecal samples were collected from
      451 household dogs, 357 dogs from breeding kennels and 351 dogs with
      gastrointestinal disorders. The samples from dogs with gastrointestinal disorders
      were sent to the diagnostic Laboratory for Parasitology at Ghent University by
      veterinary practitioners. In household dogs the prevalence of intestinal
      parasites was relatively low. Giardia was the most commonly found parasite (9.3%,
      CI 5.5-13.1), followed by Toxocara canis (4.4%, CI 2.7-6.8). Much higher
      infection rates were observed in kennel dogs, especially for Giardia spp. (43.9%,
      CI 37.8-50.0); T. canis (26.3%, CI 21.8-31.2) and Cystoisospora spp. (26.3%, CI
      21.8-31.2). Also in dogs with gastrointestinal problems, Giardia spp. (18.1%, CI
      13.1-23.1), Cystoisospora spp. (8.8%, CI 6.1-12.3) and T. canis (7.4%, CI 4.9
      10.7) were the most frequently detected parasites. In all dog populations pups
      were more frequently infected with Cystoisospora (P<0.0001 to P<0.05), Giardia
      (P<0.001 to P<0.05), and T. canis (P<0.0001 to P<0.001) than adult dogs, except
      for T. canis in household dogs, where this correlation was not significant. A
      significant association of anthelmintic treatment with T. canis infections was
      only observed within the household population. Household dogs with a higher
      number of treatments per year were more frequently infected with T. canis
      (P<0.05). There was a significant difference between the different breeding
      kennels for the occurrence of Cystoisospora, Giardia and T. canis (P<0.0001) and
      large kennels harboured relatively more infected animals than smaller breeding
      facilities (P<0.05). However, this was not significant for Giardia spp. Breed and
      gender did not affect the risk of an infection in any of the study populations.
      Toxocara and Giardia present a zoonotic risk, especially in household dogs, where
      the majority of Giardia positive samples (80%) belonged to the zoonotic
      assemblage A. In kennel dogs and clinically affected dogs the host-specific
      Giardia assemblages C and D were most prevalent (94% and 80%, respectively).

PMID- 19155137
TI  - Landscape, herd management and within-herd seroprevalence of Toxoplasma gondii in
      beef cattle herds from Champagne-Ardenne, France.
AB  - Toxoplasmosis is the most common parasitic zoonosis worldwide. Its prevalence and
      impact on human health are highly variable geographically. Humans may be infected
      by ingesting oocysts from the environment, or bradyzoits contained in meat
      products from various domestic species, thus data on the dynamics of
      toxoplasmosis in domestic herds is needed. However, few information is available
      on the factors that determine the level of infection of cattle herds. In this
      study, we aimed to estimate within-herd seroprevalence of toxoplasmosis in bovine
      herds and analyze its variability in relation with environmental characteristics
      and herd management. We tested the presence of anti Toxoplasma gondii antibodies
      in 1329 cattle from 24 beef herds in the Champagne-Ardenne region, using the
      Modified Agglutination Test. Information on herds was collected using a
      questionnaire. After describing the relationships between explanatory variables,
      we built a multivariate model using logistic Generalized Linear Models (GLMs) and
      estimated parameters with a Generalized Estimating Equations (GEE) procedure. The
      crude seroprevalence at threshold 1:24 equalled 7.8%, which is low, however
      positive individuals were found in 21 out of 24 herds. The final multivariate
      model showed that within-herd seroprevalence was highest in herds that were both
      small and isolated. The presence of cats modified the age-prevalence
      relationship: maximal seroprevalence was observed in oldest cows in farms without
      cats, and in youngest individuals in farms with cats. Finally, using a natural
      water point on pastures was associated to a high within-herd seroprevalence (Odds
      Ratio: 1.93). Cows are often exposed to toxoplasmosis, however landscape
      characteristics (water point, isolation) and herd management (herd size, cats)
      may affect seroprevalence. Our results may help to find ways of reducing T.
      gondii prevalence in cattle.

PMID- 19155138
TI  - Kinetoplast DNA heterogeneity among Leishmania infantum strains in central Israel
      and Palestine.
AB  - Leishmania infantum is the causative agent of canine and human visceral
      leishmaniasis in Israel and Palestine. Amplification of the kinetoplast DNA
      (kDNA), followed by restriction fragment length polymorphism (RFLP) analysis with
      restriction enzymes was used to examine the genotypic association between L.
      infantum strains isolated from 22 dogs and 2 humans from these adjoining regions.
      Results showed wide kDNA heterogeneity in these strains. Two main clusters (A and
      B) were identified. Cluster A was restricted to central Israel and was mainly
      found in strains isolated after 2002 whereas cluster B included parasites from
      central Israel and the West Bank. The kDNA microheterogeneity in L. infantum
      parasite populations as shown by genotyping with the kDNA-PCR and RFLP provided a
      tool to study the epidemiology of the disease and track its spread in central
      Israel and Palestine.

PMID- 19155139
TI  - Therapeutic options for elderly patients with advanced non-small cell lung
      cancer.
AB  - Elderly patients with advanced non-small cell lung cancer (NSCLC) are at higher
      risk for adverse events related to treatment of their disease. Chemotherapeutic
      agents used alone or together may increase survival, while leading to increased
      treatment related morbidity. New targeted agents used to treat NSCLC have yet to
      show sufficient improvement in disease outcomes. This review will discuss the
      current management of elderly patients with advanced non-small cell lung cancer.

PMID- 19155140
TI  - The association of hypothalamic-pituitary-adrenal axis activity and blood
      pressure in an Afro-Caribbean population.
AB  - Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPAA) resulting from
      fetal programming may play a role in the development of high blood pressure (BP)
      in black people. We assessed the diurnal salivary cortisol profile in children
      with and without increased BP and evaluated their mother's HPAA. In a cross
      sectional study, 20 Afro-Caribbean children (mean age 9.6 years) with higher
      blood pressures and 20 children with lower blood pressures were chosen from a
      prospective study of 569 mothers and children in Jamaica. Daytime salivary
      cortisol profiles were collected in the children and their mothers. The mothers
      were also assessed for features of the metabolic syndrome. Children with higher
      BP had higher mean morning salivary cortisol concentrations than those with lower
      BP (7.9 S.D. 1.9 vs. 4.5 S.D. 2.4nmol/l; p=0.03). Their mothers also had
      increased morning salivary cortisol concentrations (9.9 S.D. 1.8 vs. 5.5 S.D.
      2.5nmol/l; p=0.02), but no changes in fasting glucose, insulin, lipids, BP or
      adiposity. Maternal and offspring cortisol concentrations correlated
      significantly (r=0.465, p=0.004). Maternal cortisol concentrations were
      significantly associated with the child's BP. We conclude that Afro-Caribbean
      children with higher BP have higher morning salivary cortisol concentrations. The
      children's cortisol concentrations correlate significantly with the mother's
      cortisol concentrations. These findings suggest that the HPAA may play a role in
      the development of raised BP in Afro-Caribbean people.

PMID- 19155141
TI  - Determinants of salivary alpha-amylase in humans and methodological
      considerations.
AB  - Salivary alpha-amylase (sAA) has been proposed as a marker for activity of the
      sympathetic nervous system (SNS). Recent studies in support of this hypothesis
      have led to an increased number of researchers integrating amylase measurements
      into their study designs. Salivary alpha-amylase is produced locally in the
      salivary glands, controlled by the autonomic nervous system. This entails some
      methodological consequences and potential pitfalls that might lead to increased
      error variance and thus prevent successful testing of hypotheses. The goal of
      this review is to summarize basic and recent findings on methodological issues
      and potential factors influencing sAA measurement, and to derive a set of
      recommendations enabling researchers to successfully using sAA in
      psychoneuroendocrinological experiments.

PMID- 19155142
TI  - Peripheral nerves are progressively involved in multiple sclerosis--a hypothesis
      from a pilot study of temperature sensitized electroneurographic screening.
AB  - Multiple sclerosis (MS) is primarily a disease of the central nervous system.
      Although the involvement of the peripheral nervous system in MS was suggested
      over 100 years ago, the issue is still controversial, and it is generally
      accepted that except for the optic nerve the peripheral nerves are left
      unaffected by the disease. We hypothesize, that an electroneurographical study if
      thorough enough, may reveal differences in some nerve conduction parameters
      between MS patients and healthy subjects. Second, we assume that the sensitivity
      of nerve conduction measurements might be increased if performed at a range of
      temperatures, reflecting a differential effect of cooling and warming on the
      peripheral nerve conduction parameters in MS patients and controls. Finally, we
      expect that the differences in these parameters between controls and MS patients
      will increase with the progression of the disease. To test these hypotheses in a
      pilot study, we performed a detailed analysis of the motor and sensory nerve
      conduction features of the right median nerve in 13 MS patients and 13 controls
      at 5 degrees C increments between 20 and 40 degrees C, and repeated these
      measurements after 3 years. The motor latencies were 0.3-0.6 ms longer in MS
      patients compared to the controls both initially and 3 years later
      (0.058<p<0.09). The durations and areas of the compound motor action potential
      (CMAP) appeared more sensitive to changes in temperature in the MS group
      (0.057<p<0.1). The change in both distal motor latency and sensory latency per
      unit change in temperature decreased significantly in 3 years within the MS but
      not in the control group. These results suggest a mild and progressive
      involvement of the PNS in MS. Most differences in this pilot study were on the
      border of statistical significance therefore our hypotheses should be confirmed
      in studies with larger sample size.

PMID- 19155143
TI  - Increased UVA exposures and decreased cutaneous Vitamin D(3) levels may be
      responsible for the increasing incidence of melanoma.
AB  - Cutaneous malignant melanoma (CMM) has been increasing at a steady exponential
      rate in fair-skinned, indoor workers since before 1940. A paradox exists between
      indoor and outdoor workers because indoor workers get three to nine times less
      solar UV (290-400 nm) exposure than outdoor workers get, yet only indoor workers
      have an increasing incidence of CMM. Thus, another "factor(s)" is/are involved
      that increases the CMM risk for indoor workers. We hypothesize that one factor
      involves indoor exposures to UVA (321-400 nm) passing through windows, which can
      cause mutations and can break down vitamin D(3) formed after outdoor UVB (290-320
      nm) exposure, and the other factor involves low levels of cutaneous vitamin D(3).
      After vitamin D(3) forms, melanoma cells can convert it to the hormone, 1,25
      dihydroxyvitamin D(3), or calcitriol, which causes growth inhibition and
      apoptotic cell death in vitro and in vivo. We measured the outdoor and indoor
      solar irradiances and found indoor solar UVA irradiances represent about 25% (or
      5-10 W/m(2)) of the outdoor irradiances and are about 60 times greater than
      fluorescent light irradiances. We calculated the outdoor and indoor UV
      contributions toward different biological endpoints by weighting the emission
      spectra by the action spectra: erythema, squamous cell carcinoma, melanoma
      (fish), and previtamin D(3). Furthermore, we found production of previtamin D(3)
      only occurs outside where there is enough UVB. We agree that intense,
      intermittent outdoor UV overexposures and sunburns initiate CMM; we now propose
      that increased UVA exposures and inadequately maintained cutaneous levels of
      vitamin D(3) promotes CMM.

PMID- 19155144
TI  - Comparative study of bladder wall and myocardial remodeling.

PMID- 19155145
TI  - Xenoestrogens may be the cause of high and increasing rates of hormone receptor
      positive breast cancer in the world.
AB  - Breast cancer rates are higher in the Western or industrialized world when
      compared to Africa or Asia. Within the developing world, breast cancer rates are
      higher in urban areas where people have a more Westernized lifestyle. In
      addition, there has been a steady increase in the breast cancer incidence across
      the world. It is already a known fact that the proportion of hormone receptor
      positive breast cancer cases is higher in the developed world. Evidence from
      developed countries also shows that most of the increase in breast cancer
      incidence has been due to an increase in hormone receptor positive breast cancer.
      Most of the breast cancer incidence can be explained by environmental factors and
      genetic causes. However, all known risk factors of breast cancer can explain only
      30-50% of breast cancer incidence. In the past decade, a number of compounds that
      affect female hormone homeostasis have been discovered. These xenoestrogens have
      been shown to cause breast cancer and also induce the expression of hormone
      receptors in vitro and in vivo. Given the high use of substances containing
      xenoestrogens in developed regions of the world and their increasing use in urban
      parts of the developing world, xenoestrogens could be the important cause of high
      and increasing rates of hormone receptor positive breast cancer across the world.
      New research in the area of mammary stem cells provides added indication of the
      probable time period of exposure to xenoestrogens with chronic exposure later in
      life leading to hormone receptor positive breast cancer and most probable reason
      behind increasing breast cancer incidence.

PMID- 19155146
TI  - Hepatic composite tumor in a patient with primary sclerosing cholangitis.
AB  - A focal intrahepatic enhancing lesion with associated bile duct stricture was
      identified in a 25-year-old woman with a history of primary sclerosing
      cholangitis (PSC) who was being evaluated for increasing liver enzymes. Partial
      hepatectomy was performed, revealing a composite tumor with neuroendocrine and
      cholangiocarcinomatous differentiation. Only one composite tumor of the liver has
      been previously reported in the literature [H. Hidaka, S. Kuwao, S. Kokubu, K.
      Yanagimoto, A. Satomichi, M. Takada, T. Nakazawa, K. Saigenji, Mixed carcinoid
      adenocarcinoma of the liver, Intern. Med. 39 (2000) 910-913], and to our
      knowledge, this is the first report of such a tumor in association with PSC. We
      report this very unusual case and discuss the potential association of
      neuroendocrine carcinoma with primary sclerosing cholangitis.

PMID- 19155147
TI  - Aspects of the differential diagnosis of clear-cell lesions of the skin in
      connection with the rare case of a clear-cell atypical fibroxanthoma.
AB  - Clear-cell changes are rare in histological specimens of the dermis and raise
      complex diagnostic considerations regarding lineage differentiation (e.g.,
      epithelial, mesenchymal, or melanocytic). We present a clear-cell atypical
      fibroxanthoma (CCAFX) and describe the morphological and immunohistochemical
      aspects of this rare skin lesion. Furthermore, we give an overview of the
      differential diagnoses of clear-cell lesions of the skin for a practical
      approach.

PMID- 19155148
TI  - Microbial aetiology of acute clinical mastitis and agent-specific risk factors.
AB  - A nation wide study on the microbial aetiology of cases of acute clinical
      mastitis in Swedish dairy cows was conducted with the aim to investigate changes
      in the microbial panorama compared to a previous study performed 1994-1995.
      Another aim was to investigate some agent-specific environmental and individual
      risk factors. Milk samples were collected from 987 udder quarter cases from 829
      cows during six 2-month periods from May 2002 to April 2003, and data on risk
      factors and demography were collected at sampling by means of a questionnaire. In
      total, 1056 bacteriological diagnoses were made. The most frequently isolated
      bacterial species was Staphylococcus aureus constituting 21.3% of the diagnoses,
      followed by Escherichia coli (15.9%), Streptococcus dysgalactiae (15.6%),
      Streptococcus uberis (11.1%), coagulase-negative staphylococci (6.2%),
      Arcanobacterium pyogenes (6.1%) and Klebsiella spp. (4.2%). Samples with no
      growth or contamination constituted 10.6% and 4.5% of the diagnoses,
      respectively. A major shift in the panorama of udder pathogens was not observed
      compared to the survey in 1994-1995. Isolation of Klebsiella spp. was strongly
      associated with the use of sawdust as bedding material. On the other hand, using
      sawdust as bedding reduced the risk of isolating S. uberis relative to using
      straw or peat. The risk of isolating E. coli increased with increasing milk yield
      and was higher in loose housing systems than in tie stalls. Isolation of S.
      aureus was associated with tie stalls, and A. pyogenes with low yielding cows and
      teat lesions. S. dysgalactiae infections were also associated with teat lesions.

PMID- 19155149
TI  - [Primary school prevention program targeting cardiovascular diseases and cancers:
      "To be and to behave, the health school", assessment of an intervention involving
      2207 children].

PMID- 19155150
TI  - [Renal cell carcinoma and exposure to trichloroethylene: are the French limits of
      occupational exposure relevant?].
AB  - BACKGROUND: Several studies have investigated the association between
      trichloroethylene (TCE) exposure and renal cell cancer (RCC) but findings were
      inconsistent. The analysis of a case control study has shown an increased risk of
      RCC among subjects exposed to high cumulative exposure. The aim of this
      complementary analysis is to assess the relevance of current exposure limits
      regarding a potential carcinogenic effect of TCE on kidney. METHODS: Eighty-six
      cases and 316 controls matched for age and gender were included in the study.
      Successive jobs and working circumstances were described using a detailed
      occupational questionnaire. An average level of exposure to TCE was attributed to
      each job-period in turn. The main occupational exposures described in the
      literature as increasing the risk of RCC were assessed as well as non
      occupational factors. A conditional logistic regression was performed to test the
      association between TCE and RCC risk. Three exposure levels were studied (average
      exposure during the eight-hour shift): 35ppm, 50ppm and 75ppm. Potential
      confounding factors identified were taken into account at the threshold limit of
      10% (p=0.10) (body mass index [BMI], tobacco smoking, occupational exposures to
      cutting fluids and to other oils). RESULTS: Adjusted for tobacco smoking and BMI,
      the odd-ratios associated with exposure to TCE were respectively 1.62 [0.77
      3.42], 2.80 [1.12-7.03] and 2.92 [0.85-10.09] at the thresholds of 35ppm, 50ppm
      and 75ppm. Among subjects exposed to cutting fluids and TCE over 50ppm, the OR
      adjusted for BMI, tobacco smoking and exposure to other oils was 2.70 [1.02
      7.17]. CONCLUSION: Results from the present study as well as those provided in
      the international literature suggest that current French occupational exposure
      limits for TCE are too high regarding a possible risk of RCC.

PMID- 19155152
TI  - Therapeutic drug monitoring of everolimus using the dried blood spot method in
      combination with liquid chromatography-mass spectrometry.
AB  - An assay of everolimus based on finger prick sampling and consecutive application
      as a blood spot on sampling paper has been developed. We explored several methods
      [K. Hoogtanders, J. van der Heijden, M. Christiaans, P. Edelbroek, J. van Hooff,
      L. Stolk, J. Pharm. Biomed. Anal. 44 (2006) 658-664; A. Allanson, M. Cotton, J.
      Tettey, et al., J. Pharm. Biomed. Anal. 44 (2007) 963-969] and developed a new
      method, namely the impregnation of sampling paper with a solution of plasma
      protein, formic acid and ammonium acetate, in combination with the extraction of
      the blood spot by filter filtration. This kind of sample preparation provides new
      possibilities for blood spot sampling especially if analytes are adsorbed to the
      paper. The dried blood spot was analysed using the HPLC-electrospray-tandem mass
      spectrometry method, with 32-desmethoxyrapamycin as the internal standard. The
      working range of our study was 2-30 microg/l. Within this range, intra-and inter
      assay variability for precision and accuracy was <15%. Everolimus blood spot
      samples proved stable for 3 days at 60 degrees C and for 32 days at 4 degrees C.
      Everolimus concentrations of one stable out-patient were compared after both
      blood spot sampling and conventional venous sampling on various occasions.
      Results indicate that this new method is promising for therapeutic drug
      monitoring in stable renal transplant patients.

PMID- 19155153
TI  - Determination of impurities in heparin by capillary electrophoresis using high
      molarity phosphate buffers.
AB  - Oversulfated chondroitin sulfate (OSCS), an impurity found in some porcine
      intestinal heparin samples was separated from intact heparin by capillary
      electrophoresis (CE) using a 600mM phosphate buffer, pH 3.5 as the background
      electrolyte in a 56cm x 25microm i.d. capillary. This method was confirmed in two
      separate labs, was shown to be linear, reproducible, robust, easy to use and
      provided the highest resolution and superior limits of detection compared to
      other available CE methods. Glycosoaminoglycans such as dermatan sulfate and
      heparan sulfate were separated and quantified as well during a single run. The
      heparin peak area response correlated well to values obtained using the official
      assay for biological activity. A high speed, high resolution version of the
      method was developed using 600mM lithium phosphate, pH 2.8 in a 21.5cm x 25microm
      i.d. capillary which provided limits of detection for OSCS that were below 0.1%.

PMID- 19155154
TI  - Determination of two COX-2 inhibitors in serum and synovial fluid of patients
      with inflammatory arthritis by ultra performance liquid chromatography
      inductively coupled plasma mass spectroscopy and quadrupole time-of-flight mass
      spectrometry.
AB  - The determination of two sulphur-containing drugs, the COX-2 inhibitors celecoxib
      and etoricoxib, in the serum and synovial fluid of inflammatory arthritis
      patients, is described using a sensitive ultra performance liquid chromatography
      inductively coupled plasma mass spectroscopy (UPLC/ICPMS) method. Confirmation of
      the identity of the analytes in the samples was also performed by electrospray
      quadruple time-of-flight mass spectrometry in positive electrospray ionisation
      mode. The two COX-2 inhibitors were extracted from serum and synovial fluid
      following dilution with acetate buffer (pH 5) and liquid-liquid extraction (LLE)
      into ethyl acetate. Extracted samples were then analysed using UPLC/ICPMS with
      sulphur-specific detection. The limit of detection by UPLC/ICPMS was 0.45 ng/ml
      of sulphur in both serum and synovial fluid. The UPLC/ICPMS method was applied to
      the analysis of samples from patients receiving either 200 mg/day of celecoxib
      (2x 100 mg), 90 mg/day etoricoxib or placebo. The range of concentrations
      detected in the samples for the two drugs was from 0.3 to 3.3 microg/ml.

PMID- 19155155
TI  - Effectiveness of education for gastric cancer patients: a controlled prospective
      trial comparing interactive vs. lecture-based programs.
AB  - OBJECTIVE: Although patient education may enhance knowledge, coping with illness,
      and quality of life among cancer patients, it is uncertain which didactic method
      is most effective. We compared the impact of an interactive, patient-oriented
      group program to a lecture-based, information-only program in gastric cancer
      patients. METHODS: In this prospective, controlled trial, 121 gastric cancer
      patients attending inpatient rehabilitation after surgical treatment received
      either the interactive intervention or lectures providing information. The
      outcomes were patients' disease-related knowledge, active coping with illness,
      and quality of life (QoL) at the end of their stay and 6 and 12 months
      thereafter. RESULTS: Both groups improved their knowledge and QoL during
      rehabilitation; however, knowledge was significantly higher in the interactive
      group compared to the lecture group. This difference was maintained at the 6- and
      12-months follow-ups. In addition, the interactive group proved superior to the
      lecture group regarding active coping with illness and QoL at the end of
      rehabilitation, but not during follow-up. CONCLUSIONS: A structured, interactive
      patient education program proved superior to lecture-based provision of
      information in regards to short-term and long-term knowledge as well as short
      term coping and QoL. PRACTICE IMPLICATIONS: In gastric cancer patients,
      interactive patient education seems preferable over lectures.

PMID- 19155156
TI  - Combined EEG/fMRI recording in musicogenic epilepsy.
AB  - Seizures induced by musical stimulation are usually correlated to temporal
      epilepsy, although the precise localization of their epileptogenic networks are
      not well characterized. Brain imaging studies show that regional cerebral blood
      flow (rCBF) recorded during musicogenic seizures is increased in putative
      epileptogenic foci, as well as in other brain regions not directly related to
      seizure activity. These studies, however, afford only a virtual temporal relation
      between ictal discharges and rCBF changes, given that brain images are correlated
      with off-line EEG recordings. To obviate this problem, the simultaneous
      multimodal recording of the episode of musicogenic epilepsy is mandatory. The
      present study describes the EEG-fMRI co-recording of musicogenic elicited
      seizures in a case of simple partial epilepsy. Our results show that EEG features
      recorded in epileptogenic areas are largely coupled with rCBF increase.
      Furthermore, rCBF modifications in other regions suggest that additional aspects
      of musical processing are also elicited during musicogenic seizures.

PMID- 19155157
TI  - Local hyperthermia could induce migrational maturation of Langerhans cells in
      condyloma acuminatum.

PMID- 19155158
TI  - A study of the antimicrobial activity of selected naturally occurring and
      synthetic coumarins.
AB  - The antimicrobial activities of 43 naturally occurring and synthetic coumarins
      were studied. Using a microtitre assay developed in-house, a range of Gram
      positive and Gram-negative bacteria, including a hospital isolate of methicillin
      resistant Staphylococcus aureus (MRSA),were utilised. The coumarins exhibiting
      good bioactivity (i.e. a low minimum inhibitory concentration) against two S.
      aureus strains were then assessed for their antimicrobial activities against a
      range of eight clinically isolated MRSA strains. The study showed that nearly one
      half of the tested compounds displayed antimicrobial activity. Sixteen of these
      coumarins also possessed resistance-modifying activity, which reversed the
      resistance mechanism in MRSA allowing the antimicrobial oxacillin to exert an
      enhanced effect against an MRSA hospital strain. When tested in combination with
      oxacillin, 8-iodo-5,7-dihydroxycoumarin (32) had a similar activity to
      vancomycin, which is the current drug of choice for the treatment of MRSA
      infections.

PMID- 19155159
TI  - In vitro combination of cefotaxime and ciprofloxacin against non-typhoid
      salmonellae.

PMID- 19155160
TI  - SILA 421, an inhibitor of efflux pumps of cancer cells, enhances the killing of
      intracellular extensively drug-resistant tuberculosis (XDR-TB).
AB  - Multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR-TB) are
      problematic to manage, especially in patients with acquired immune deficiency
      syndrome (AIDS). There is therefore a dire need for effective anti-MDR/XDR-TB
      agents. We have previously shown that agents that inhibit the efflux pumps of MDR
      bacteria and cancer cells also enhance killing of intracellular mycobacteria,
      possibly by increasing the availability of K(+) and Ca(2+) needed for the
      activation of lysosomal enzymes of the phagolysosomal unit. In this study, the
      newly synthesised and recently patented SILA 409 and 421 were tested for in vitro
      and ex vivo activity against XDR-TB. The minimum inhibitory concentration (MIC)
      of SILA compounds was determined by the BACTEC 460 TB system. The effect of each
      compound on the killing activity of human macrophages infected with XDR-TB was
      determined by exposing the macrophage that had phagocytosed the bacterium to the
      compounds and assessing the killing activity by colony-forming unit counting.
      Amongst the two compounds tested, SILA 421 was shown to have in vitro activity
      against XDR-TB (MIC<3.5mg/L) and to transform non-killing macrophages into
      effective killers of phagocytosed bacteria, without any cytotoxic activity.
      Because SILA 421 revealed good in vitro and ex vivo activities and is devoid of
      any cytotoxic activity, it is a potential candidate as an anti-MDR/XDR-TB drug.

PMID- 19155161
TI  - Construction of anticoagulant poly (lactic acid) films via surface covalent graft
      of heparin-carrying microcapsules.
AB  - Heparin has been widely investigated in medicine and biomedical applications as
      an anticoagulant. This paper described a covalent modification of poly (lactic
      acid) (PLA) films with heparin-carrying microcapsules. The heparin-carrying
      microcapsules were achieved by layer-by-layer (LbL) self-assembly technology by
      which poly (allylamine hydrochloride) (PAH) and heparin were alternately coated
      on the Ca(2+)-cross-linked alginate hydrogel. The microcapsules were
      characterized by scanning electron microscopy (SEM), zeta potential analysis and
      Fourier transform infrared spectroscopy (FTIR), and then grafted to PLA films by 
      CONH- linkage between surface PLA molecules with residual primary amino groups on
      the outer PAH layer of microcapsules, in the presence of catalysts of 1-ethyl-3
      (3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). SEM
      and FTIR revealed the formation of -CONH- linkage. In vitro antithrombogenicity
      by the method of the activated partial thromboplastin time (APTT), prothrombin
      time (PT) and thrombin time (TT) tests showed that surface-modified PLA films had
      superior coagulation properties to original PLA films. It is suggested that the
      present method would provide a potential effective tool for biomaterial
      modification.

PMID- 19155162
TI  - Filtration of Bacillus subtilis and Bacillus cereus spores in a pyroclastic
      topsoil, carbonate Apennines, southern Italy.
AB  - A comparative study on the filtration of Bacillus subtilis and Bacillus cereus
      spores in a pyroclastic topsoil was performed in laboratory using surfactant-free
      solutions and solutions with the surfactant sodium dodecyl sulphate (SDS)
      (anionic). The results of the column experiments demonstrate that the SDS does
      not significantly influence the retention of both B. subtilis and B. cereus
      spores. Since the SDS is adsorbed through hydrophobic interaction with the
      organic matter of soil media, these results suggest that hydrophobic interaction
      between spores and organic matter does not play a significant role on filtration
      processes within the studied topsoil. This statement is of utmost importance
      taking into consideration the hydrophobic nature of Bacillus spores and the very
      high organic matter content in the studied topsoil (20-34%). Conversely, the
      retention of the analyzed spores seems to be influenced by the pore size
      exclusion phenomenon.

PMID- 19155163
TI  - Stabilizing dispersions of hydrophobic drug molecules using cellulose ethers
      during anti-solvent synthesis of micro-particulates.
AB  - Anti-solvent synthesis of micro-scale drug particles with simultaneous suspension
      stabilization using different cellulose ethers and a surfactant (SDS) is
      reported. The process was very effective under low power ultrasonic agitation.
      The mean diameter of the small particles grew with time, while the overall
      particle size distribution showed a decrease in average particle size due to
      sedimentation. The result showed that a combination of cellulose ether and SDS
      reduced the average particle size more effectively than either only cellulose
      ether or SDS. The sedimentation rate was also the lowest when both the cellulose
      ether and SDS were used. At the end of nine hours, as much as 74.6% of the drug
      Fenofibrate, and 56.0% of the drug griseofulvin remained in stable suspension in
      drug/HPMC/SDS systems. Zeta potential measurements showed that the suspensions
      were close to agglomeration rather than thermodynamically stable. Melting point
      measurements showed that cellulose ether was not a major component of the
      particle, while scanning electron microscopy revealed particle shapes and degree
      of the agglomeration. Raman spectroscopy also confirmed the presence of the drug
      molecule in these crystals.

PMID- 19155164
TI  - Modelling, analysis and optimization of adsorption parameters for H3PO4 activated
      rubber wood sawdust using response surface methodology (RSM).
AB  - Adsorption capacity of Cu(2+) from aqueous solution onto H(3)PO(4) activated
      carbon using rubber wood sawdust (RSAC) was investigated in a batch system.
      Kinetic and isotherm studies were carried out, the thermodynamic parameters like
      standard Gibb's free energy (Delta G degrees), enthalpy (Delta H degrees) and
      entropy (DeltaS degrees) were evaluated. The pseudo-second-order model was found
      to explain the kinetics of Cu(2+) adsorption most effectively. The process
      optimization was performed through Central Composite Rotary Design using response
      surface methodology (RSM) by Design Expert Version 5.0.7 (STAT-EASE Inc.,
      Minneapolis, USA). An initial concentration of 35 mg L(-1), temperature of 26
      degrees C, carbon loading of 0.45 g(100mL)(-1), adsorption time 208 min and pH of
      6.5 was found to be the optimum conditions for the maximum uptake of copper ions
      of 5.6 mg g(-1) in batch mode.

PMID- 19155165
TI  - Evaluation of the efficiency of metabolism of dinoflagellate phosphorus and
      carbon by a planktonic ciliate.
AB  - The trophic transfer of nutrients through the microbial food web is a key top
      down control in aquatic ecosystems which is notoriously difficult to evaluate,
      particularly for planktonic protists. In this study, a sensitive dual-radioactive
      tracer technique was developed to simultaneously assess the ingestion rate, and
      carbon- and phosphorus-specific assimilation efficiencies, of the marine
      planktonic ciliate Strobilidium neptuni feeding on the autotrophic dinoflagellate
      Heterocapsa triquetra. Dinoflagellate prey were simultaneously 16h pulse labelled
      with NaH(14)CO(3) and H(3)(33)PO(4) before being fed to the ciliate, and
      radioactive labels were traced into ciliate biomass and the experimental medium,
      as well as being monitored in the prey cells. Rates measured in short-term
      (10min) incubations, as commonly used to estimate protist uptake of fluorescently
      labelled prey, were approximately 6 times higher and 3-6 times more variable than
      rates measured in longer 3-5h incubations. The efficiency of accumulation of prey
      carbon (54+/-9%) by ciliates was lower than that of prey phosphorus (68+/-3%)
      suggesting that the phosphorus to carbon ratio in the ciliates was 1.3 times
      higher than in the labelled dinoflagellate biomass. Rates of phosphorus
      accumulation and release were combined to reveal that ciliates consumed 3.2+/-0.6
      dinoflagellates cell(-1)h(-1). The assessment of carbon tracer release by
      ciliates was less reliable due to (14)CO(2) exchange between the experimental
      media and air. The study concludes that the dual phosphorus-carbon radioactive
      tracer labelling of algal prey allowed the quantification of protist herbivory
      and nutrient remineralisation in laboratory experiments, thereby providing a
      potential technique for studying planktonic microbial trophic interactions in
      situ.

PMID- 19155166
TI  - Effects of Bothrops asper snake venom on the expression of cyclooxygenases and
      production of prostaglandins by peritoneal leukocytes in vivo, and by isolated
      neutrophils and macrophages in vitro.
AB  - In this study, the ability of Bothrops asper snake venom (BaV) to increase the
      production of prostaglandins PGE(2) and PGD(2) was assessed in a mouse model in
      vivo and in inflammatory cells in vitro. In addition, the expressions of COX-1
      and COX-2 were assessed. BaV induced an increment in the in vivo synthesis of
      PGE(2) and PGD(2), together with an enhanced expression of COX-2, but not of COX
      1. However, enzymatic activities of COX-1 and COX-2 were increased. Incubation of
      isolated macrophages and neutrophils with a sub-cytotoxic concentration of BaV in
      vitro resulted in increased release of PGE(2) and PGD(2) by macrophages and
      PGE(2) by neutrophils, concomitantly with an increment in the expression of COX
      2, but not of COX-1 by both cell types. Our results demonstrate the ability of
      BaV to promote the expression of COX-2 and to induce the synthesis of
      proinflammatory prostaglandins. Macrophages and neutrophils may be important
      targets for this venom under in vivo situation.

PMID- 19155167
TI  - Health-related quality of life in adult survivors of childhood sarcoidosis.
AB  - AIM: To describe health-related quality of life (hrQOL) in adult subjects who had
      sarcoidosis in childhood. METHODS: Forty-six children (24 boys), all ethnic Danes
      <or=15 years of age with sarcoidosis were recorded in Denmark in 1979-1994. Three
      patients were deceased prior to this study. At follow-up, the 43 surviving adult
      subjects were invited to complete the short-form health survey questionnaire SF
      36, being completed by 34 subjects (14 men). SF-36 scores were compared with the
      scores in the Danish reference population. RESULTS: At follow-up, 30/34 patients
      had recovered from sarcoidosis and 4/34 patients had persistent chronic active
      disease with impaired lung function. SF-36 scores in all domains were similar to
      scores in the reference population; the four patients with chronic active disease
      had lower scores in three domains. In the entire series, physical component
      summary (PCS) score and mental component summary (MCS) score was similar to the
      reference population. CONCLUSION: Childhood sarcoidosis has a favourable
      prognosis concerning health status in adulthood. The majority of adult subjects
      had a health status that was indistinguishable from a healthy reference
      population.

PMID- 19155168
TI  - A systematic review of integrated use of disease-management interventions in
      asthma and COPD.
AB  - BACKGROUND: The effectiveness of multiple interventions in asthma and chronic
      obstructive pulmonary disease (COPD) is unclear. OBJECTIVE: To examine the
      effectiveness of multiple interventions as compared to single interventions or
      usual care on health outcomes and health care utilisation within the context of
      integrated disease management in asthma and COPD. METHODS: MEDLINE and the
      Cochrane Library (1995-May 2008) were searched for controlled trials. Two
      reviewers independently extracted data and assessed study quality. Meta-analyses
      were performed on quality of life and health care utilisation data. Furthermore,
      the effects of multiple interventions versus single interventions and usual care
      were assessed qualitatively. RESULTS: Of the 36 studies included, 17 targeted
      double interventions (patient-related and organisational interventions); 19
      studies performed triple interventions (patient-related, professional-directed
      and organisational interventions). They were heterogeneous in terms of
      (combinations of) interventions, outcomes measured, study design and setting.
      Pooled data showed that studied disease management programmes significantly
      improved quality of life on several domains. Patients within triple intervention
      programmes had less chance of at least one hospital admission compared with usual
      care. No significant effects were found in number of emergency department visits.
      Qualitative analyses revealed positive trends on process improvements and
      satisfaction. Inconclusive results were reported on symptoms; no effects were
      found in lung function. CONCLUSION: In spite of the heterogeneity of disease
      management studies in asthma and COPD care, this review showed promising
      improvements in quality of life and reductions in hospitalisations, especially
      for triple intervention programmes.

PMID- 19155169
TI  - Selective separation of virgin and post-consumer polymers (PET and PVC) by
      flotation method.
AB  - More and more polymer wastes are generated by industry and householders today.
      Recycling is an important process to reduce the amount of waste resulting from
      human activities. Currently, recycling technologies use relatively homogeneous
      polymers because hand-sorting waste is costly. Many promising technologies are
      being investigated for separating mixed thermoplastics, but they are still
      uneconomical and unreliable. At present, most waste polymers cause serious
      environmental problems. Burning polymers for recycling is not practiced since
      poisonous gases are released during the burning process. Particularly, polyvinyl
      chloride (PVC) materials among waste polymers generate hazardous HCl gas, dioxins
      containing Cl, etc., which lead to air pollution and shorten the life of the
      incinerator. In addition, they make other polymers difficult to recycle. Both
      polyethylene terephthalate (PET) and PVC have densities of 1.30-1.35g /cm(3) and
      cannot be separated using conventional gravity separation techniques. For this
      reason, polymer recycling needs new techniques. Among these techniques, froth
      flotation, which is also used in mineral processing, can be useful because of its
      low cost and simplicity. The main objective of this research is to recycle PET
      and PVC selectively from post-consumer polymer wastes and virgin polymers by
      using froth flotation. According to the results, all PVC particles were floated
      with 98.8% efficiency in virgin polymer separation while PET particles were
      obtained with 99.7% purity and 57.0% efficiency in post-consumer polymer
      separation.

PMID- 19155170
TI  - Glutamate sensing with enzyme-modified floating-gate field effect transistors.
AB  - Neurotransmitter release is the key factor of chemical messaging in the brain.
      Fast, sensitive and in situ detection of single cell neurotransmitter release is
      essential for the investigation of synaptic transmission under physiological or
      pathophysiological conditions. Although various techniques have been developed
      for detecting neurotransmitter release both in vitro and in vivo, the sensing of
      such events still remains challenging. First of all, the amount of
      neurotransmitter released during synaptic transmission is unknown because of the
      limited number of molecules released and the fast diffusion and reuptake of these
      molecules after release. On the other hand, advances in microelectronic biosensor
      devices have made possible the fast detection of various analytes with high
      sensitivity and selectivity. Specifically, enzyme-modified field-effect (ENFET)
      devices are attractive for such applications due to their fast response, small
      dimensions and the possibility to integrate a large number of sensors on the same
      chip. In this paper, we present a floating-gate FET device coated with glutamate
      oxidase (GLOD) layer. The surface chemistry was optimized for maximal enzyme
      loading and long-term stability, and characterized by quartz crystal microbalance
      and colorimetric assays. Enzyme loading was largest on poly-L-lysin-based
      surfaces combined with glutaraldehyde. The surface chemistry showed excellent
      stability for at least one month in Tris buffers stored at 4 degrees C. A
      glutamate detection limit of 10(-7) M has been obtained with the GLOD-coated FET
      and our sensor proved to be selective to glutamate only. We show that this
      biosensor is a promising tool for the in vitro detection of glutamate and can be
      extended to other neurotransmitters.

PMID- 19155171
TI  - Detection of known base substitution mutations in human mitochondrial DNA of
      MERRF and MELAS by biochip technology.
AB  - We developed a DNA biochip specialized for detection of known base substitution
      mutations in mitochondrial DNA causing mitochondrial encephalomyopathy, lactic
      acidosis and stroke-like episodes (MELAS) and myoclonic epilepsy associated with
      ragged-red fibers (MERRF). A set of probes sharing a given allele-specific
      sequence with a single base substitution near the middle of the sequence was
      covalently immobilized. Cy5-labeled DNA targets were amplified from sample DNAs
      containing 31 potential MELAS and/or MERRF mutations by a multiplex PCR method.
      Detection parameters for the DNA biochip-based assay were accordingly optimized.
      Seven clinically confirmed patients with MELAS, 5 patients with MERRF, 1
      suspected MERRF case and 25 healthy controls were tested using the DNA biochip.
      For discriminating of homoplasmic and heteroplasmic point mutations in mtDNA, a
      diagnostic factor based on the ratio between the hybridization signals from the
      reference and test targets with each probe was used. The results showed that all
      the cases with MELAS had a causal heteroplasmic A3243G tRNA(Leu(UUR)) mutation.
      In the MERRF patients, four cases were found to be a homoplasmic A8344G tRNA(Lys)
      mutation and one case was a heteroplasmic T8356C tRNA(Lys) mutation. None of the
      healthy controls carried the potential mutations. The results of the DNA biochip
      were completely consistent with those by DNA sequencing. Thus, the DNA biochip
      would potentially become a valuable tool in clinical specific screening of the
      mtDNA point mutations associated with MELAS and/or MERRF syndrome.

PMID- 19155172
TI  - The impact of landfilling and composting on greenhouse gas emissions--a review.
AB  - Municipal solid waste is a significant contributor to greenhouse gas emissions
      through decomposition and life-cycle activities processes. The majority of these
      emissions are a result of landfilling, which remains the primary waste disposal
      strategy internationally. As a result, countries have been incorporating
      alternative forms of waste management strategies such as energy recovery from
      landfill gas capture, aerobic landfilling (aerox landfills), pre-composting of
      waste prior to landfilling, landfill capping and composting of the organic
      fraction of municipal solid waste. As the changing global climate has been one of
      the major environmental challenges facing the world today, there is an increasing
      need to understand the impact of waste management on greenhouse gas emissions.
      This review paper serves to provide an overview on the impact of landfilling (and
      its various alternatives) and composting on greenhouse gas emissions taking into
      account streamlined life cycle activities and the decomposition process. The
      review suggests greenhouse gas emissions from waste decomposition are
      considerably higher for landfills than composting. However, mixed results were
      found for greenhouse gas emissions for landfill and composting operational
      activities. Nonetheless, in general, net greenhouse gas emissions for landfills
      tend to be higher than that for composting facilities.

PMID- 19155173
TI  - A novel medium for the production of cephamycin C by Nocardia lactamdurans using
      solid-state fermentation.
AB  - In this study, Nocardia lactamdurans NRRL 3802 was explored for the first time
      for production of cephamycin C by using solid-state fermentation. The effects of
      various substrates, moisture content, inoculum size, initial pH of culture
      medium, additional nitrogen source and amino acids were investigated for the
      maximum production of cephamycin C by N. lactamdurans NRRL 3802 in solid-state
      fermentation. Subsequently, selected fermentation parameters were further
      optimized by response surface methodology (RSM). The soybean flour as a substrate
      with moisture content of 65%, initial pH of culture medium of 6.5 and inoculum
      size of 10(9)CFU/ml (2 x 10(8)CFU/gds) at 28+/-2 degrees C after 4 days gave
      maximum production of 15.75+/-0.27 mg/gds of cephamycin C as compared to 8.37+/
      0.23 mg/gds before optimization. Effect of 1,3-diaminopropane on cephamycin C
      production was further studied, which further increased the yield to 27.64+/-0.33
      mg/gds.

PMID- 19155174
TI  - Development of thioquinazolinones, allosteric Chk1 kinase inhibitors.
AB  - A high throughput screening campaign was designed to identify allosteric
      inhibitors of Chk1 kinase by testing compounds at high concentration. Activity
      was then observed at K(m) for ATP and at near-physiological concentrations of
      ATP. This strategy led to the discovery of a non-ATP competitive
      thioquinazolinone series which was optimized for potency and stability. An X-ray
      crystal structure for the complex of our best inhibitor bound to Chk1 was solved,
      indicating that it binds to an allosteric site approximately 13A from the ATP
      binding site. Preliminary data is presented for several of these compounds.

PMID- 19155175
TI  - Absence of beta-tropomyosin is a new cause of Escobar syndrome associated with
      nemaline myopathy.
AB  - While TPM2 mutations identified so far in muscular diseases were all associated
      with a dominant inheritance pattern, we report the identification of a homozygous
      null allele mutation in the TPM2 gene in a patient who presented with a recessive
      form of nemaline myopathy associated with a non-lethal multiple pterygium
      syndrome (Escobar-MPS MIM# 265000). The TPM2 mutation led to a complete absence
      of the skeletal muscle isoform of beta-tropomyosin not compensated by expression
      of other beta-tropomyosin isoforms. Escobar syndrome has been recently described
      as a prenatal form of myasthenia associated with recessive mutations in genes of
      the neuromuscular junction (CHRNG, CHRNA1, CHRND, RAPSN). This observation
      expands the cause of Escobar variant-MPS to a component of the contractile
      apparatus. This first report of the clinical expression of the complete absence
      of TPM2 in human indicated that TPM2 expression at the early period of prenatal
      life plays a major role for normal fetal movements.

PMID- 19155176
TI  - The ineffectiveness of fibrin glue and cyanoacrylate on fixation of meniscus
      transplants in rabbits.
AB  - Our aim was to evaluate whether a fibrin glue and octyl-cyanoacrylate can promote
      fixation of meniscal allograft in rabbits. The medial menisci of 18 rabbits were
      frozen and stored at -73 degrees C (30 days) and then was allotransplantation and
      fixed by: GSu (n=6) soft tissue; GFi (n=6) fibrin glue; GCy (n=6) cyanoacrylate.
      They were evaluated by daily surgery recovery score (4 weeks), gross inspection
      and cells density on scaffold. A severe inflammatory response with caseous
      necrosis from the inside of the joint on through the approach incision led us to
      an early sacrifice (16th day) of all animals of GCy. The daily score of recovery
      was similar in both groups GSu and GFi, with a peak of 40% of mild suffering
      score in the 12th day. At the 4th week in all animals of GFi the menisci were
      loose into the joint and the density of cells of collagen matrix was
      significantly fewer (p<0.001) than the GSu. The octyl-cyanoacrylate adhesive was
      totally inadequate for use on fixation of an allograft implant due to the severe
      inflammatory response. The fibrin glue was inappropriate to promote the allograft
      fixation and subsequently impaired the cells spread into the collagen matrix of
      allograft implant.

PMID- 19155177
TI  - Synthesis and evaluation of ligands for D2-like receptors: the role of common
      pharmacophoric groups.
AB  - Arylcycloalkylamines, such as phenyl piperidines and piperazines and their
      arylalkyl substituents, constitute pharmacophoric groups exemplified in several
      antipsychotic agents. A review of previous reports indicates that arylalkyl
      substituents can improve the potency and selectivity of the binding affinity at
      D(2)-like receptors. In this paper, we explored the contributions of two key
      pharmacophoric groups, that is, 4'-fluorobutyrophenones and 3-methyl-7
      azaindoles, to the potency and selectivity of synthesized agents at D(2)-like
      receptors. Preliminary observation of binding affinities indicates that there is
      little predictability of specific effects of the arylalkyl moieties but the
      composite structure is responsible for selectivity and potency at these
      receptors.

PMID- 19155178
TI  - Measurements of the 82Sr half-life.
AB  - Half-life of (82)Sr was measured at the National Institute of Standards and
      Technology (NIST) using gamma-ray spectrometry and a 4pigamma pressurized
      ionization chamber. The (82)Sr half-life was found to be 25.36+/-0.03 days (k=1)
      according to gamma-ray spectrometry and 25.34+/-0.02 days (k=1) according to the
      4pigamma pressurized ionization chamber measurements.

PMID- 19155179
TI  - Application of a new chair-side method for the harvest of mesenchymal stem cells
      in a patient with nonunion of a fracture of the atrophic mandible--a case report.
AB  - PURPOSE: This case report describes a new clinical method for chair-side
      processing of a cell mixture which contains mesenchymal stem cells (MSCs) which
      was applied for the first time in the treatment of a nonunion of an atrophic
      fractured mandible. METHODS: Bone marrow was aspirated and a corticocancellous
      bone graft was harvested from the iliac crest of a 56-year-old woman with medical
      comorbidities and a fracture of the atrophic mandible. The fracture was
      stabilized with a reconstruction bone plate, and mononuclear cells including MSCs
      were concentrated by centrifugation and applied in combination with a particulate
      bone transplant. A sample of the grafted cells was characterized by flow
      cytometric analysis and by their ability to differentiate into various cell
      types. RESULTS: The fracture healed uneventfully. No complications occurred
      during the 4-month follow-up. CONCLUSION: Adding MSCs is a feasible alternative
      to enhance bone healing. This chair-side method requires little training and no
      cell laboratory support.

PMID- 19155180
TI  - Relationships between body composition, muscular strength, and bone mineral
      density in estrogen-deficient postmenopausal women.
AB  - The purpose of this study was to examine relationships between muscular strength,
      body composition, and bone mineral density (BMD) in untrained postmenopausal
      women who are not on hormone replacement therapy (HRT). Fifty-five women (age:
      63.3+/-0.6yr) completed menstrual history, physical activity, and calcium intake
      questionnaires. Total and regional body composition and total body,
      anteroposterior lumbar spine, nondominant forearm, and right proximal femur BMD
      were measured using dual-energy X-ray absorptiometry (DXA) (GE Lunar Prodigy,
      Prodigy enCORE software version 10.50.086, Madison, WI). Participants performed
      strength tests for 3 upper body and 5 lower body resistance exercises. Women with
      a relative skeletal muscle mass index (RSMI) value less than 5.45 kg/m(2) were
      defined as a sarcopenia group (SAR). SAR had significantly (p < 0.05) lower total
      body and forearm BMD compared with those who were not sarcopenic. BMD sites were
      significantly correlated with upper body strength (UBS) and lower body strength
      (LBS) (r = 0.28-0.50, p < 0.01), with the strength of relationship being site
      specific. Strength and fat mass (FM) significantly predicted total body BMD (R(2)
      = 0.232-0.241, p < 0.05), FM variables predicted spine BMD (R(2) = 0.109-0.140, p
      < 0.05), and LBS and RSMI predicted hip BMD sites (R(2) = 0.073-0.237, p < 0.05).
      Body composition variables failed to significantly predict LBS. In conclusion,
      the contribution of body composition and strength variables to BMD varied by site
      as FM was more important for total body, forearm and spine BMD, and LBS exerted
      greater influence on the hip sites.

PMID- 19155181
TI  - Single-dose pharmacokinetics and genotoxicity of metronidazole in cats.
AB  - Single-dose pharmacokinetics and genotoxicity of metronidazole in cats were
      evaluated. Cats received either 5mg/kg metronidazole intravenously, or 20mg/kg
      metronidazole benzoate (12.4mg/kg metronidazole base) orally in a single dose.
      Serial plasma samples were collected and assayed for metronidazole using high
      pressure liquid chromatography (HPLC). Genotoxicity was assessed in vitro in
      feline peripheral blood mononuclear cells (PBMC) and a feline T-cell lymphoma
      line incubated with metronidazole, and in vivo in PBMC collected before, during
      and 7 days after oral metronidazole, by use of the COMET assay. Systemic
      absorption of metronidazole was variable (mean=65+/-28%) with a peak of 8.84+/
      5.4microg/ml at 3.6+/-2.9h. The terminal half-life was 5.34h from the intravenous
      dose and 5.16h from the oral dose. Systemic clearance was low (mean=91.57ml/h/kg
      [1.53ml/kg/min]), and the apparent volume of distribution (steady state) was
      0.650+/-0.254l/kg. Genotoxicity was detected at all concentrations of
      metronidazole in feline PBMC and the T-cell lymphoma line in vitro. Genotoxicity
      was also observed in PBMC collected from cats after 7 days of oral metronidazole
      but resolved within 6 days of discontinuing metronidazole.

PMID- 19155182
TI  - Crimean-Congo hemorrhagic fever in Greece: a public health perspective.
AB  - In June 2008 the first non-imported fatal case of Crimean-Congo hemorrhagic fever
      (CCHF) was recorded in northern Greece. We present herein the public health
      interventions and the case definitions we developed for the epidemiological
      investigation. The possibility of CCHF establishing endemicity in this area is
      discussed.

PMID- 19155183
TI  - Fatal disseminated Mycobacterium simiae infection in a non-HIV patient.
AB  - We report a fatal case of disseminated Mycobacteriumsimiae infection in an
      immunocompetent elderly man with fever of unknown origin. The diagnosis was based
      on culture isolation of non-tuberculous mycobacteria from cerebrospinal fluid and
      bronchoalveolar lavage. Both culture isolates were identified as M. simiae by 16S
      rRNA gene sequencing.

PMID- 19155184
TI  - Bladder irrigation with amphotericin B and fungal urinary tract infection-
      systematic review with meta-analysis.
AB  - BACKGROUND: Candiduria is a hospital-associated infection and a daily problem in
      the intensive care unit. The treatment of asymptomatic candiduria is not well
      established and the use of amphotericin B bladder irrigation (ABBI) is
      controversial. The aim of this systematic review was to determine the best place
      for this therapy in practice. METHODS: The databases searched in this study
      included MEDLINE, EMBASE, Web of Science, and LILACS (January 1960-June 2007). We
      included manuscripts with data on the treatment of candiduria using ABBI. The
      studies were classified as comparative, dose-finding, or non-comparative.
      RESULTS: From 213 studies, nine articles (377 patients) met our inclusion
      criteria. ABBI showed a higher clearance of the candiduria 24 hours after the end
      of therapy than fluconazole (odds ratio (OR) 0.57, 95% confidence interval (CI)
      0.32-1.00). Fungal culture 5 days after the end of both therapies showed a
      similar response (OR 1.51, 95% CI 0.81-2.80). The evaluation of ABBI using an
      intermittent or continuous system of delivery showed an early candiduria
      clearance (24 hours after therapy) of 80% and 82%, respectively (OR 0.87, 95% CI
      0.52-1.36). Candiduria clearance at >5 days after the therapy showed a superior
      response using continuous bladder irrigation with amphotericin B (OR 0.52, 95% CI
      0.29-0.94). The use of continuous ABBI for more than 5 days showed a better
      result (88% vs. 78%) than ABBI for less than 5 days, but without significance (OR
      0.55, 95% CI 0.34-1.04). CONCLUSION: Although the strength of the results in the
      underlying literature is not sufficient to allow the drawing of definitive
      conclusions, ABBI appears to be as effective as fluconazole, but it does not
      offer systemic antifungal therapy and should only be used for asymptomatic
      candiduria.

PMID- 19155185
TI  - Infection with H274Y-positive influenza A (H1N1) is not associated with a change
      in nasopharyngeal Streptococcus pneumoniae colonization in patients.

PMID- 19155186
TI  - ESX/type VII secretion systems and their role in host-pathogen interaction.
AB  - The ESX-1 system is responsible for the secretion of the prototypic ESX proteins,
      namely the 6 kDa early secreted antigenic target (ESAT-6) and the 10 kDa culture
      filtrate protein (CFP-10). These two proteins, which form a 1:1 heterodimeric
      complex, are among the most important proteins of Mycobacterium tuberculosis
      involved in host-pathogen interaction. They induce a strong T cell mediated
      immune response, are apparently involved in membrane and/or host-cell lysis and
      represent key virulence factors. There are four other paralogous ESX systems in
      M. tuberculosis, some of which are essential for in vitro growth. ESX systems
      also exist in many other actinobacteria and Gram-positive bacteria, and have
      recently been suggested to be named type VII secretion systems.

PMID- 19155187
TI  - Flow injection chemiluminescence method for the determination of pentoxyverine
      citrate based on NCS-dichlorofluorescein post-chemiluminescence reaction.
AB  - A post-chemiluminescence (PCL) phenomenon was observed when pentoxyverine citrate
      solution was injected into the reaction mixture after the finish of
      chemiluminescence (CL) reaction of N-chlorosuccinimide (NCS) and alkaline
      dichlorofluorescein. The possible reaction mechanism was proposed based on the
      studies of the CL kinetic characteristics, the CL spectra and the fluorescence
      spectra of some related substances. Based on the PCL reaction, a rapid and
      sensitive method for the determination of pentoxyverine citrate was established.
      The linear response range of this method was from 6.0x10(-9) to 1.0x10(-6)gmL(-1)
      with a linear correlation coefficient of 0.9998. The relative standard deviation
      for 2.0x10(-8)gmL(-1) pentoxyverine citrate was 2.1% (n=11). The detection limit
      was 9x10(-10)gmL(-1). This method has been applied to the determination of
      pentoxyverine citrate in human plasma and pharmaceutical samples with the
      satisfactory results.

PMID- 19155188
TI  - Study on discrimination of Roast green tea (Camellia sinensis L.) according to
      geographical origin by FT-NIR spectroscopy and supervised pattern recognition.
AB  - Rapid discrimination of roast green tea according to geographical origin is
      crucial to quality control. Fourier transform near-infrared (FT-NIR) spectroscopy
      and supervised pattern recognition was attempted to discriminate Chinese green
      tea according to geographical origins (i.e. Anhui Province, Henan Province,
      Jiangsu Province, and Zhejiang Province) in this work. Four supervised pattern
      recognitions methods were used to construct the discrimination models based on
      principal component analysis (PCA), respectively. The number of principal
      components factors (PCs) and model parameters were optimized by cross-validation
      in the constructing model. The performances of four discrimination models were
      compared. Experimental results showed that the performance of SVM model is the
      best among four models. The optimal SVM model was achieved when 4 PCs were used,
      discrimination rates being all 100% in the training and prediction set. The
      overall results demonstrated that FT-NIR spectroscopy with supervised pattern
      recognition could be successfully applied to discriminate green tea according to
      geographical origins.

PMID- 19155189
TI  - Spectroscopic studies on the interaction of Congo Red with bovine serum albumin.
AB  - The binding interaction of Congo Red (CGR) with bovine serum albumin (BSA) was
      investigated by spectroscopic techniques including fluorescence spectroscopy, UV
      vis absorption, and circular dichroism (CD) spectroscopy under simulative
      physiological conditions. Fluorescence data revealed that the fluorescence
      quenching of BSA by CGR was the result of the formation of a BSA-CGR complex, and
      the corresponding binding constants (K(a)) at the four different temperatures
      (292, 298, 304, and 310K) were obtained according to the modified Stern-Volmer
      equation. The thermodynamic parameters DeltaH and DeltaS were calculated to be 
      12.67kJmol(-1) and 58.60Jmol(-1)K(-1), respectively, which suggested that both
      hydrophobic force and hydrogen bond played major roles in stabilizing the BSA-CGR
      complex. Site marker competitive experiments showed that the binding of CGR to
      BSA primarily took place in site I of BSA. The distance r between CGR (acceptor)
      and tryptophan residues of BSA (donor) was calculated to be 3.89nm based on
      Forster's non-radioactive energy transfer theory. The conformational
      investigation showed that the presence of CGR resulted in the change of BSA
      secondary structure and induced the slight unfolding of the polypeptides of
      protein, which confirmed some micro-environmental and conformational changes of
      BSA molecules.

PMID- 19155190
TI  - Computational study of steric and spectroscopic characteristics of bi
      chromophoric cyanine dyes: comparison with experimental data.
AB  - The spectral and energetic characteristics of four bi-chromophoric cyanine dyes
      (BCDs) which possess angles between chromophores 180 degrees , 150 degrees , 120
      degrees and 90 degrees , were studied using quantum chemical calculations in
      comparison with experimental data. It was demonstrated that for BCD with 180
      degrees , 150 degrees and 90 degrees trans-trans isomers possess the lowest
      energy, while for BCD with 120 degrees the trans-trans and cis-trans isomers have
      comparable energies and in the temperature range from 273K up to 373K both
      isomers of this dye are present. It was also demonstrated that the splitting of
      the spectra of cyanine dyes with two chromophores (BCD) was determined by two
      effects: the dipole-dipole chromophore interaction and the electron tunneling
      through the central heterocycle. Both effects depend on the central heterocycle
      structure, which on the one hand determines the distance between the
      chromophores, thus determining the value of the dipole-dipole interaction, and on
      the other hand the degree of pi-conjugation in the central heterocycle determines
      the probability of electron tunneling. The central heterocycle structure
      determines relative orientation of the chromophore dipoles, as well, thus
      determining the intensities of the short-wavelength and long-wavelength bands in
      the BCD absorption spectra.

PMID- 19155191
TI  - Opiate and cocaine addiction: from bench to clinic and back to the bench.
AB  - This review primarily focuses on our recent findings in bidirectional
      translational research on opiate and cocaine addictions. First, we present
      neurobiological and molecular studies on endogenous opioid systems (e.g.
      proopiomelanocortin, mu opioid receptor, dynorphin, and kappa opioid receptor),
      brain stress-responsive systems (e.g. orexin, arginine vasopressin, V1b receptor,
      and corticotropin-releasing factor), hypothalamic-pituitary-adrenal axis, and
      neurotransmitters (especially dopamine), in response to both chronic cocaine or
      opiate exposure and to drug withdrawal, using several newly developed animal
      models and molecular approaches. The second aspect is human molecular genetic
      association investigations including hypothesis-driven studies and genome-wide
      array studies, to define particular systems involved in vulnerability to develop
      specific addictions, and response to pharmacotherapy.

PMID- 19155192
TI  - Using an online case conference to facilitate interprofessional learning.
AB  - Interprofessional learning is seen as increasingly important for all health and
      social care workers. How this is integrated into the education of these workers
      is less clear and more of a challenge. This article describes an online learning
      activity used to facilitate interprofessional learning in a Faculty of Health and
      Social Care in the UK. An online conference was used to bring students together,
      utilising a real life case scenario based around a family within a virtual town.
      Students from a variety of programmes and professional groups participated in an
      asynchronous discussion forum. The student evaluation of this event was, on the
      whole, positive and suggests further development of such an approach would
      address some of the challenges of interprofessional learning.

PMID- 19155193
TI  - Clinical laboratory evaluation of autoimmune autonomic ganglionopathy:
      Preliminary observations.
AB  - Several forms of chronic autonomic failure manifest as neurogenic orthostatic
      hypotension, including autoimmune autonomic ganglionopathy (AAG) and pure
      autonomic failure (PAF). AAG and PAF are thought to differ in pathogenesis, AAG
      reflecting decreased ganglionic neurotransmission due to circulating antibodies
      to the neuronal nicotinic receptor and PAF being a Lewy body disease with
      prominent loss of sympathetic noradrenergic nerves. AAG therefore would be
      expected to differ from PAF in terms of clinical laboratory findings indicating
      post-ganglionic noradrenergic denervation. Both diseases are rare. Here we report
      preliminary observations about clinical physiologic, neuropharmacologic,
      neurochemical, and neuroimaging data that seem to fit with the hypothesized
      pathogenetic difference between AAG and PAF. Patients with either condition have
      evidence of baroreflex-sympathoneural and baroreflex-cardiovagal failure. Both
      disorders feature low plasma levels of catecholamines during supine rest, but
      plasma levels of the other endogenous catechols, dihydroxyphenylalanine (DOPA),
      dihydroxyphenylacetic acid (DOPAC), and dihydroxyphenylglycol (DHPG), seem to be
      lower in PAF than in AAG, probably reflecting decreased norepinephrine synthesis
      and turnover in PAF, due to diffuse sympathetic noradrenergic denervation. PAF
      entails cardiac sympathetic denervation, whereas cardiac sympathetic neuroimaging
      by thoracic 6-[(18)F]fluorodopamine scanning indicates intact myocardial
      sympathetic innervation in AAG.

PMID- 19155194
TI  - Image of the month. Emergency presentation of a giant pedunculated liver
      haemangioma.

PMID- 19155197
TI  - A major regulatory centre.

PMID- 19155195
TI  - How are we diagnosing cardiometabolic risk in primary care settings?
AB  - AIMS: To assess attitudes, barriers and practices of clinicians in assessing and
      treating cardiometabolic risk in overweight adults. METHODS: In 2006, primary
      care physicians and mid-level practitioners in Montana were surveyed (N=430).
      RESULTS: Most primary care clinicians (95%) recognized the clinical benefit of
      weight loss, but many cited patient motivation (87%), lack of support services
      (61%), and lack of time (58%) as barriers. Over 80% identified obesity,
      hypertension, abnormal lipids, history of gestational diabetes, and family
      history as indications for diabetes screening. Most clinicians used fasting
      glucose (89%), random glucose (58%), and A1c (42%) as initial screens for
      diabetes. To confirm the diagnosis, the majority of respondents used A1c testing
      (80%) or fasting glucose (64%). Approximately one-quarter used the diagnosis pre
      diabetes (26%), but just over half (52%) used alternative diagnoses of glucose
      intolerance. Sixty-five percent used the diagnosis of metabolic syndrome. Of
      those using metabolic syndrome, mid-level practitioners were more likely than
      physicians to assess waist circumference (49% vs. 63%). CONCLUSIONS: Despite
      citing significant barriers, clinicians routinely assessed cardiometabolic risk
      with diabetes screening, but relatively few reported using the diagnosis pre
      diabetes. Metabolic syndrome was used commonly to diagnose overweight adults at
      risk for diabetes and cardiovascular disease.

PMID- 19155198
TI  - Molecular biology of androgen-independent prostate cancer: the role of the
      androgen receptor pathway.
AB  - Prostate cancer (PC) cells express the androgen receptor (AR) and need the
      presence of androgens to survive. Androgen suppression is the gold standard first
      line therapy for metastatic disease. Almost all PC patients initially respond to
      hormonal therapy, but most of them gradually develop resistance to castration.
      There is evidence that these tumours that are considered castration-resistant
      continue to depend on AR signalling. Several mechanisms that enhance AR
      signalling in an androgen-depleted environment have been elucidated: (1) AR
      mutations that allow activation by low androgen levels or by other endogenous
      steroids, (2) AR amplification and/or overexpression, (3) increased local
      intracrine synthesis of androgens, (4) changes in AR cofactors and (5) cross-talk
      with cytokines and growth factors. Today, there are a number of novel agents
      targeting the AR signalling pathway under development, including more effective
      antiandrogens; inhibitors of CYP17, inhibitors of HSP90, inhibitors of histone
      deacetylases and inhibitors of tyrosine kinase inhibitors.

PMID- 19155199
TI  - Notch signalling in cancer stem cells.
AB  - A new theory about the development of solid tumours is emerging from the idea
      that solid tumours, like normal adult tissues, contain stem cells (called cancer
      stem cells) and arise from them. Genetic mutations encoding for proteins involved
      in critical signalling pathways for stem cells such as BMP, Notch, Hedgehog and
      Wnt would allow stem cells to undergo uncontrolled proliferation and form
      tumours. Taking into account that cancer stem cells (CSCs) would represent the
      real driving force behind tumour growth and that they may be drug resistant, new
      agents that target the above signalling pathways could be more effective than
      current anti-solid tumour therapies. In the present paper we will review the
      molecular basis of the Notch signalling pathway. Additionally, we will pay
      attention to their role in adult stem cell self-renewal, and cell fate
      specification and differentiation, and we will also review evidence that supports
      their implication in cancer.

PMID- 19155200
TI  - Surgical treatment for hepatocellular carcinoma in cirrhotic patients. Guide to
      the selection and decision-making process in a context of multimodal strategy.
AB  - Hepatocellular carcinoma (HCC) is the fifth most frequent malignant tumour and
      the third leading cause of death due to cancer worldwide [1]. Surgical treatment
      is the only long-term curative therapy. But the resection rate remains low in
      cirrhotic patients due to contraindications imposed mainly by hepatic
      insufficiency and excessively advanced tumoral stages. In recent years, however,
      due to the extended use of screening programmes in high-risk patients, tumours
      are smaller at presentation, making treatments easier. In the current context of
      shortage of organs for transplantation, surgical resection remains the best
      available treatment option for most patients with HCC in cirrhotic livers.
      Despite the encouraging results reported by several groups in terms of overall
      survival, the high recurrence rate is still an unsolved problem. Recently, a
      large, randomised, placebo-controlled trial has shown that a multikinase
      inhibitor targeting Ras-kinase and VEGFR-2, sorafenib, improves survival of
      patients with advanced HCC. Sorafenib was approved by regulatory agencies during
      2007 and is likely to become the new standard therapy for HCC patients with
      advanced disease.

PMID- 19155201
TI  - Radiofrequency thermocoagulation of lung tumours. Where we are, where we are
      headed.
AB  - Only 25% of all lung cancers are diagnosed in an early stage allowing surgical
      treatment. Primary tumours usually concerning lung metastasis are breast, colon,
      kidney, uterus/cervix, prostate, and head and neck tumours. During recent years
      many publications have confirmed the effectiveness and reliability of lung
      radiofrequency ablation (RFA) alone or together with other techniques
      (chemotherapy, radiotherapy...). Results suggest that survival increase and
      curative rates of lung radiofrequency are similar to those achieved by more
      aggressive procedures and present lower rates of complications. Pneumothorax,
      pleural effusion and alveolar haemorrhage are the most frequent complications.
      Indications for lung RFA must be individually evaluated by lung cancer
      committees. Percutaneous lung RFA may be useful in patients with pulmonary
      primary tumours and metastases, especially in those with nodules smaller than 3
      cm and a peripheral location (>1 cm from the hilum). PET/CT seems to be the most
      accurate technique in patient follow up.

PMID- 19155202
TI  - Management of platinum-resistant ovarian cancer with the combination of
      pemetrexed and gemcitabine.
AB  - INTRODUCTION: Platinum resistant ovarian cancer is a current challenge in
      Oncology. Current approved therapies offer no more of a 20% of response. New
      therapeutic options are urgently needed. PATIENTS AND METHODS: Patients were
      treated with the combination of Pemetrexed 500 mg/m(2) d1 and Gemcitabine 1000
      mg/m(2) d1,8 in a 21 days basis. RESULTS: 10 platinum-resistant ovarian cancer
      patients were treated under compassionate use. Mean previous chemotherapy lines
      were 3.3. Mean administered cycles were 4. Mean CA 125 decrease was on average of
      47%, with one patient experiencing a 95% decrease in her CA 125 level. 1 patient
      had a complete clinical remission, and 2, had partial radiological responses.
      Mean Progression free survival was 16.5 weeks, and Overall Survival was 21.2
      weeks. Treatment was well tolerated. CONCLUSIONS: Deemd to the observed activity,
      the combination of Pemetrexed and Gemcitabine deserves deeper investigation in
      platinum-resistant ovarian cancer patients.

PMID- 19155203
TI  - Cost-effectiveness analysis of docetaxel (Taxotere) vs. 5-fluorouracil in
      combined therapy in the initial phases of breast cancer.
AB  - INTRODUCTION: The randomised controlled trial BCIRG001 has recently demonstrated
      that docetaxel in combination with doxorubicin and cyclophosphamide (TAC) has
      better efficacy than the standard treatment (FAC, i.e., 5-fluorouracil,
      doxorubicin and cyclophosphamide) in the adjuvant treatment of patients with node
      positive breast cancer. The cost-effectiveness of TAC vs. FAC in the Spanish
      setting is analysed. PATIENTS AND METHODS: Clinical outcomes from trial BCIRG001
      were combined with Spanish costs and longterm efficacy of FAC and TAC
      extrapolated up to 5 years by means of a Markov model. Results are shown as cost
      per life year gained (C/LYG) and cost per quality-adjusted life year (C/QALY).
      Costs and effects were discounted at a rate of 3%. RESULTS: Mean survival was
      17.8 and 16.5 years for TAC and FAC, with total costs of euro14,611 and
      euro11,586, respectively. The results of the cost-effectiveness analysis showed
      that TAC achieves a C/LYG and a C/QALY of only euro2345 and euro2631,
      respectively. Sensitivity analysis confirmed the robustness of the results.
      CONCLUSIONS: Combined therapy based on docetaxel (TAC) is not only an effective
      option, but also presents a favourable cost-effectiveness ratio, clearly below
      the Spanish efficiency threshold in all the scenarios considered.

PMID- 19155204
TI  - Outcome of treating advanced neuroendocrine tumours with radiolabelled
      somatostatin analogues.
AB  - OBJECTIVES: To evaluate the initial response and outcomes (quality of life and
      presence of side effects) in patients with advanced neuroendocrine tumours (NET)
      after treatment with radiolabelled somatostatin analogues: (90)Y-DOTATyr3-
      octreotide ((90)Y-DOTATOC) and (177)Lu-DOTA-Tyr3- octreotate ((177)Lu-DOTATATE).
      MATERIAL AND METHODS: The study included 5 patients with advanced NET referred to
      European centres for treatment with (90)Y-DOTATOC and (177)Lu-DOTATATE after lack
      of response to conventional treatment. The mean age was 45.6 years (29-68 years).
      Response to therapy was assessed according to: (1) RECIST criteria, as complete
      response, partial response, stable disease or disease progression, (2) post
      treatment survival time and (3) quality of life, using the Karnofsky performance
      index. RESULTS: All patients survived for >20 months after treatment; mean
      survival time was 28 months. At the time of writing, three of the patients are
      alive after 20, 26 and 37 months. Partial response was observed in one patient,
      stable disease in three and disease progression in the fifth patient. A good-to
      excellent post-treatment quality of life was observed in all patients.
      CONCLUSION: Therapy with radiolabelled somatostatin analogues showed promising
      results in patients with advanced NET, with a partial response or disease
      stabilisation in four of the five patients, who have enjoyed an extended survival
      period and an improved quality of life.

PMID- 19155206
TI  - Pancreatic glucagonoma presenting as a pulmonary mass.
AB  - Glucagonoma is an uncommon disease, a neuroendocrine tumour that develops from
      glucagon-producing pancreatic cells. They are usually slow-growing, but generally
      advanced at diagnosis, and metastatic disease is virtually incurable. Liver is
      the most common site of metastatic disease. We present the case of a 48-year-old
      man with a glucagonoma being diagnosed from a pulmonary mass. This case had no
      liver affection in the whole evolution of the disease, and showed a particularly
      aggressive course, with very little response to all therapies administered, and a
      survival from diagnosis of just 16 months.

PMID- 19155205
TI  - Doxorubicin and cyclophosphamide followed by weekly docetaxel as neoadjuvant
      treatment of early breast cancer: analysis of biological markers in a GEICAM
      phase II study.
AB  - INTRODUCTION: To evaluate the sequential administration of doxorubicin (A) and
      cyclophosphamide (C) followed by weekly docetaxel in women with stage II to IIIA
      breast cancer. PATIENTS AND METHODS: Patients received 60 mg/m(2) of A and 600
      mg/m(2) of C every three weeks for four cycles followed by 12 infusions of weekly
      docetaxel at a dose of 36 mg/m(2) and with a 2-week resting period. RESULTS:
      Sixty-three women were included. On an intention-to- treat basis, clinical
      response rate was 90% (95% CI: 83-98), with 46% complete responses. Breast
      conserving surgery could be performed in 43 patients (68%). Complete pathological
      responses in the breast were confirmed in 17% of patients. No correlations
      between levels of expression of topoisomerase II alpha, survivin or p27 and the
      pathological response were detected. The study treatment was generally well
      tolerated. CONCLUSION: Neoadjuvant AC followed by weekly docetaxel is a feasible
      regimen for patients with early-stage breast cancer.

PMID- 19155207
TI  - Brain metastases from prostate adenocarcinoma.
AB  - Brain metastases of prostate adenocarcinoma are rare. We report a case of brain
      metastases from prostate adenocarcinoma 15 months after the diagnosis of the
      primary tumour. The patient had headache and one solitary metastasis upon
      magnetic resonance imaging (MRI). The biopsy performed showed metastatic prostate
      adenocarcinoma. He was treated with surgery and cranial irradiation.

PMID- 19155208
TI  - Identification of new p53 acetylation sites in COS-1 cells.
AB  - The p53 tumor suppressor protein is a key regulator of cell cycle and death that
      is involved in many cell signaling pathways and is tightly regulated in mammalian
      cells. Post-translational modifications of p53 have been investigated previously
      mainly using antibodies. In this study, utilizing LC-MS/MS analysis, we have
      characterized p53 protein from COS-1 cells. Several already known post
      translational modifications were observed, such as phosphorylation on serines 15,
      33, 315, and 392 as well as acetylation on lysines 305, 370, 372, 373, 381, 382,
      and 386. Interestingly novel acetylation sites were identified at lysines 319 and
      357. This study confirmed that p53 is a highly acetylated protein and revealed
      new acetylation sites that might aid the further understanding of p53 regulation.

PMID- 19155209
TI  - Enhancing identifications of lipid-embedded proteins by mass spectrometry for
      improved mapping of endothelial plasma membranes in vivo.
AB  - Lipid membranes structurally define the outer surface and internal organelles of
      cells. The multitude of proteins embedded in lipid bilayers are clearly
      functionally important, yet they remain poorly defined. Even today, integral
      membrane proteins represent a special challenge for current large scale shotgun
      proteomics methods. Here we used endothelial cell plasma membranes isolated
      directly from lung tissue to test the effectiveness of four different mass
      spectrometry-based methods, each with multiple replicate measurements, to
      identify membrane proteins. In doing so, we substantially expanded this
      membranome to 1,833 proteins, including >500 lipid-embedded proteins. The best
      method combined SDS-PAGE prefractionation with trypsin digestion of gel slices to
      generate peptides for seamless and continuous two-dimensional LC/MS/MS analysis.
      This three-dimensional separation method outperformed current widely used two
      dimensional methods by significantly enhancing protein identifications including
      single and multiple pass transmembrane proteins; >30% are lipid-embedded
      proteins. It also profoundly improved protein coverage, sensitivity, and dynamic
      range of detection and substantially reduced the amount of sample and the number
      of replicate mass spectrometry measurements required to achieve 95% analytical
      completeness. Such expansion in comprehensiveness requires a trade-off in heavy
      instrument time but bodes well for future advancements in truly defining the ever
      important membranome with its potential in network-based systems analysis and the
      discovery of disease biomarkers and therapeutic targets. This analytical strategy
      can be applied to other subcellular fractions and should extend the
      comprehensiveness of many future organellar proteomics pursuits.

PMID- 19155211
TI  - Insulin regulates fusion of GLUT4 vesicles independent of Exo70-mediated
      tethering.
AB  - Insulin regulates cellular glucose uptake by changing the amount of glucose
      transporter-4 (GLUT4) in the plasma membrane through stimulation of GLUT4
      exocytosis. However, how the particular trafficking, tethering, and fusion steps
      are regulated by insulin is still debated. In a 3T3-L1 adipocyte cell line, the
      Exocyst complex and its Exo70 subunit were shown to critically affect GLUT4
      exocytosis. Here we investigated the effects of Exo70 on tethering and fusion of
      GLUT4 vesicles in primary isolated rat adipose cells. We found that Exo70 wild
      type was sequestered away from the plasma membrane in non-stimulated cells, and
      its overexpression had no effect on GLUT4 trafficking. The addition of insulin
      increased the amount of Exo70 in the vicinity of the plasma membrane and
      stimulated the tethering and fusion of GLUT4 vesicles, but the rates of fusion
      and GLUT4 exposure were not affected by overexpression of Exo70. Surprisingly,
      the Exo70-N mutant induced insulin-independent tethering of GLUT4 vesicles,
      which, however, did not lead to fusion and exposure of GLUT4 at the plasma
      membrane. Upon insulin stimulation, the stationary pretethered GLUT4 vesicles in
      Exo70-N mutant cells underwent fusion without relocation. Taken together, our
      data suggest that fusion of GLUT4 vesicles is the rate-limiting step regulated by
      insulin downstream of Exo70-mediated tethering.

PMID- 19155210
TI  - Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a
      neurogenic component.
AB  - Limb-girdle muscular dystrophy type 2H (LGMD2H) and sarcotubular myopathy are
      hereditary skeletal muscle disorders caused by mutations in TRIM32. We previously
      identified TRIM32 as an E3 ubiquitin ligase that binds to myosin and
      ubiquitinates actin. To date four TRIM32 mutations have been linked to LGMD2H,
      all of which occur in the C-terminal NHL domains. Unexpectedly, a fifth mutation
      in the B-box of TRIM32 causes a completely different, multisystemic disorder,
      Bardet-Biedl syndrome type 11. It is not understood how allelic mutations in
      TRIM32 can create such diverse phenotypic outcomes. To generate a tool for
      elucidating the complex in vivo functions of TRIM32, we created the first murine
      Trim32 knock-out model (T32KO). Histological analysis of T32KO skeletal muscles
      revealed mild myopathic changes. Electron microscopy showed areas with Z-line
      streaming and a dilated sarcotubular system with vacuoles -- the latter being a
      prominent feature of sarcotubular myopathy. Therefore, our model replicates
      phenotypes of LGMD2H and sarcotubular myopathy. The level of Trim32 expression in
      normal mouse brain exceeds that observed in skeletal muscle by more than 100
      times, as we demonstrated by real-time PCR. Intriguingly, analysis of T32KO
      neural tissue revealed a decreased concentration of neurofilaments and a
      reduction in myelinated motoraxon diameters. The axonal changes suggest a shift
      toward a slower motor unit type. Not surprisingly, T32KO soleus muscle expressed
      an elevated type I slow myosin isotype with a concomitant reduction in the type
      II fast myosin. These data suggest that muscular dystrophy due to TRIM32
      mutations involves both neurogenic and myogenic characteristics.

PMID- 19155212
TI  - The Electron Transfer Pathway of the Na+-pumping NADH:Quinone Oxidoreductase from
      Vibrio cholerae.
AB  - The Na(+)-pumping NADH:quinone oxidoreductase (Na(+)-NQR) is the only respiratory
      enzyme that operates as a Na(+) pump. This redox-driven Na(+) pump is amenable to
      experimental approaches not available for H(+) pumps, providing an excellent
      system for mechanistic studies of ion translocation. An understanding of the
      internal electron transfer steps and their Na(+) dependence is an essential
      prerequisite for such studies. To this end, we analyzed the reduction kinetics of
      the wild type Na(+)-NQR, as well as site-directed mutants of the enzyme, which
      lack specific cofactors. NADH and ubiquinol were used as reductants in separate
      experiments, and a full spectrum UV-visible stopped flow kinetic method was
      employed. The results make it possible to define the complete sequence of redox
      carriers in the electrons transfer pathway through the enzyme. Electrons flow
      from NADH to quinone through the FAD in subunit F, the 2Fe-2S center, the FMN in
      subunit C, the FMN in subunit B, and finally riboflavin. The reduction of the
      FMN(C) to its anionic flavosemiquinone state is the first Na(+)-dependent
      process, suggesting that reduction of this site is linked to Na(+) uptake. During
      the reduction reaction, two FMNs are transformed to their anionic
      flavosemiquinone in a single kinetic step. Subsequently, FMN(C) is converted to
      the flavohydroquinone, accounting for the single anionic flavosemiquinone radical
      in the fully reduced enzyme. A model of the electron transfer steps in the
      catalytic cycle of Na(+)-NQR is presented to account for the kinetic and
      spectroscopic data.

PMID- 19155213
TI  - Molecular Insight into the Synergism between the Minor Allele of Human Liver
      Peroxisomal Alanine:Glyoxylate Aminotransferase and the F152I Mutation.
AB  - Human liver peroxisomal alanine:glyoxylate aminotransferase (AGT) is a pyridoxal
      5'-phosphate (PLP)-dependent enzyme that converts glyoxylate into glycine. AGT
      deficiency causes primary hyperoxaluria type 1 (PH1), a rare autosomal recessive
      disorder, due to a marked increase in hepatic oxalate production. Normal human
      AGT exists as two polymorphic variants: the major (AGT-Ma) and the minor (AGT-Mi)
      allele. AGT-Mi causes the PH1 disease only when combined with some mutations. In
      this study, the molecular basis of the synergism between AGT-Mi and F152I
      mutation has been investigated through a detailed biochemical characterization of
      AGT-Mi and the Phe(152) variants combined either with the major (F152I-Ma, F152A
      Ma) or the minor allele (F152I-Mi). Although these species show spectral
      features, kinetic parameters, and PLP binding affinity similar to those of AGT
      Ma, the Phe(152) variants exhibit the following differences with respect to AGT
      Ma and AGT-Mi: (i) pyridoxamine 5'-phosphate (PMP) is released during the overall
      transamination leading to the conversion into apoenzymes, and (ii) the PMP
      binding affinity is at least 200-1400-fold lower. Thus, Phe(152) is not an
      essential residue for transaminase activity, but plays a role in selectively
      stabilizing the AGT-PMP complex, by a proper orientation of Trp(108), as
      suggested by bioinformatic analysis. These data, together with the finding that
      apoF152I-Mi is the only species that at physiological temperature undergoes a
      time-dependent inactivation and concomitant aggregation, shed light on the
      molecular defects resulting from the association of the F152I mutation with AGT
      Mi, and allow to speculate on the responsiveness to pyridoxine therapy of PH1
      patients carrying this mutation.

PMID- 19155214
TI  - Histone H3 lysine 36 dimethylation (H3K36me2) is sufficient to recruit the Rpd3s
      histone deacetylase complex and to repress spurious transcription.
AB  - Histone methylation is associated with both transcription activation and
      repression. However, the functions of different states of methylation remain
      largely elusive. Here, using methyl-lysine analog technology, we demonstrate that
      the histone deacetylase complex, Rpd3S, can distinguish the nucleosomes
      methylated to different extents and that K36me2 is sufficient to target Rpd3S in
      vitro. Through a genome-wide survey, we identified a few mutants in which the
      level of K36me3 is significantly reduced, whereas the level of K36me2 is
      sustained. Transcription analysis and genome-wide histone modification studies on
      these mutants suggested that K36me2 is sufficient to target Rpd3S in vivo,
      thereby maintaining a functional Set2-Rpd3S pathway.

PMID- 19155215
TI  - Structural characterization of the bradyzoite surface antigen (BSR4) from
      Toxoplasma gondii, a unique addition to the surface antigen glycoprotein 1
      related superfamily.
AB  - Toxoplasma gondii is an obligate intracellular protozoan parasite that infects
      nearly one-third of the human population. The success of T. gondii is based on
      its complex life cycle; a lytic tachyzoite form disseminates infection, whereas
      an encysted bradyzoite form establishes a latent, chronic infection. Persistence
      and transmissibility is central to the survival of the parasite and is, in part,
      mediated by a family of antigenically distinct surface antigen glycoprotein (SAG)
      related sequences (SRS) adhesins that play a dual role in host cell attachment
      and host immune evasion. More than 160 members of the SRS family have been
      identified with only the tachyzoite-expressed SAG1 structurally characterized.
      Here we report the first structural description of the bradyzoite adhesin BSR4
      using x-ray crystallography and small angle x-ray scattering. The 1.90-A crystal
      structure of BSR4 reveals an architecture comprised of tandem beta sandwich
      domains organized in a head to tail fashion with the N-terminal domain
      responsible for dimer formation. A restructured topology in BSR4 results in a
      ligand-binding site that is significantly reorganized in both structure and
      chemistry relative to SAG1, consistent with BSR4 binding a distinct physiological
      ligand. The small angle x-ray scattering solution structure of BSR4 highlights a
      potentially important structural role for the interdomain polymorphic linker that
      imparts significant flexibility that may promote structural adaptation during
      ligand binding. This study reveals an unexpected level of structural diversity
      within the SRS superfamily and provides important insight into the role of these
      virulence factors.

PMID- 19155216
TI  - Surfactant protein A modulates cell surface expression of CR3 on alveolar
      macrophages and enhances CR3-mediated phagocytosis.
AB  - Pulmonary surfactant protein A (SP-A), a member of the collectin family, plays an
      important role in innate immune defense of the lung. In this study, we examined
      the role of SP-A in modulating complement receptor-mediated phagocytosis.
      Complement receptors (CR), CR3 (CD11b), and CR4 (CD11c) were expressed at reduced
      levels on the surface of alveolar macrophages from Sp-a(-/-) compared with Sp
      a(+/+) mice. Administration of intratracheal SP-A to Sp-a(-/-) mice induced the
      translocation of CR3 from alveolar macrophage intracellular pools to the cell
      surface. Intratracheal challenge with Haemophilus influenza enhanced CR3
      expression on the surface of alveolar macrophages from Sp-a(-/-) and Sp-a(+/+)
      mice, but relative expression remained lower in the Sp-a(-/-) mice at all time
      points post-inoculation. The effects of SP-A on macrophage and neutrophil CR3
      redistribution between intracellular and cell surface pools were restricted to
      cells isolated from the lung. SP-A augmented CR3-mediated phagocytosis in a
      manner that was attenuated by N-glycanase or collagenase treatment of SP-A,
      implicating the N-linked sugar and collagen-like domains in that function. The
      binding of CR3 to SP-A was calcium dependent and mediated by the I-domain of CR3
      and to a lesser extent by the CR3 lectin domain. Mapping of the domains of SP-A
      that were required for optimal binding to CR3 revealed that the N-linked sugars
      were more critical than the collagen-like domain or the extent of oligomeric
      assembly. We conclude that SP-A modulates the cell surface expression of CR3 on
      alveolar macrophages, binds to CR3, and enhances CR3-mediated phagocytosis.

PMID- 19155217
TI  - Ribosomal protein S19 interacts with macrophage migration inhibitory factor and
      attenuates its pro-inflammatory function.
AB  - Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has
      been implicated in the pathogenesis of inflammatory disorders such as infection,
      sepsis, and autoimmune disease. MIF exists preformed in cytoplasmic pools and
      exhibits an intrinsic tautomerase and oxidoreductase activity. MIF levels are
      elevated in the serum of animals and patients with infection or different
      inflammatory disorders. To elucidate how MIF actions are controlled, we searched
      for endogenous MIF-interacting proteins with the potential to interfere with key
      MIF functions. Using in vivo biotin-tagging and endogenous co
      immunoprecipitation, the ribosomal protein S19 (RPS19) was identified as a novel
      MIF binding partner. Surface plasmon resonance and pulldown experiments with wild
      type and mutant MIF revealed a direct physical interaction of the two proteins
      (K(D) = 1.3 x 10(-6) m). As RPS19 is released in inflammatory lesions by
      apoptotic cells, we explored whether it affects MIF function and inhibits its
      binding to receptors CD74 and CXCR2. Low doses of RPS19 were found to strongly
      inhibit MIF-CD74 interaction. Furthermore, RPS19 significantly compromised CXCR2
      dependent MIF-triggered adhesion of monocytes to endothelial cells under flow
      conditions. We, therefore, propose that RPS19 acts as an extracellular negative
      regulator of MIF.

PMID- 19155218
TI  - FBP17 Mediates a Common Molecular Step in the Formation of Podosomes and
      Phagocytic Cups in Macrophages.
AB  - Macrophages act to protect the body against inflammation and infection by
      engaging in chemotaxis and phagocytosis. In chemotaxis, macrophages use an actin
      based membrane structure, the podosome, to migrate to inflamed tissues. In
      phagocytosis, macrophages form another type of actin-based membrane structure,
      the phagocytic cup, to ingest foreign materials such as bacteria. The formation
      of these membrane structures is severely affected in macrophages from patients
      with Wiskott-Aldrich syndrome (WAS), an X chromosome-linked immunodeficiency
      disorder. WAS patients lack WAS protein (WASP), suggesting that WASP is required
      for the formation of podosomes and phagocytic cups. Here we have demonstrated
      that formin-binding protein 17 (FBP17) recruits WASP, WASP-interacting protein
      (WIP), and dynamin-2 to the plasma membrane and that this recruitment is
      necessary for the formation of podosomes and phagocytic cups. The N-terminal EFC
      (extended FER-CIP4 homology)/F-BAR (FER-CIP4 homology and Bin-amphiphysin-Rvs)
      domain of FBP17 was previously shown to have membrane binding and deformation
      activities. Our results suggest that FBP17 facilitates membrane deformation and
      actin polymerization to occur simultaneously at the same membrane sites, which
      mediates a common molecular step in the formation of podosomes and phagocytic
      cups. These results provide a potential mechanism underlying the recurrent
      infections in WAS patients.

PMID- 19155219
TI  - Novel localization of callose in the spores of Physcomitrella patens and
      phylogenomics of the callose synthase gene family.
AB  - BACKGROUND AND AIMS: Callose involvement in spore development is a plesiomorphic
      feature of land plants. Correlated light, fluorescence and immuno-electron
      microscopy was conducted on the developing spores of Physcomitrella patens to
      probe for callose. Using a bioinformatic approach, the callose synthase (PpCalS)
      genes were annotated and PpCalS and AtCalS gene families compared, testing the
      hypothesis that an exine development orthologue is present in P. patens based on
      deduced polypeptide similarity with AtCalS5, a known exine development gene.
      METHODS: Spores were stained with aniline blue fluorescent dye. Capsules were
      prepared for immuno-light and immuno-electron microscopy by gold labelling
      callose epitopes with monoclonal antibody. BLAST searches were conducted using
      the AtCalS5 sequence as a query against the P. patens genome. Phylogenomic
      analysis of the CalS gene family was conducted using PAUP (v.4.1b10). KEY
      RESULTS: Callose is briefly present in the aperture of developing P. patens
      spores. The PpCalS gene family consists of 12 copies that fall into three
      distinct clades with AtCalS genes. PpCalS5 is an orthologue to AtCalS5 with
      highly conserved domains and 64 % similarity of their deduced polypeptides.
      CONCLUSIONS: This is the first study to identify the presence of callose in moss
      spores. AtCalS5 was previously shown to be involved in pollen exine development,
      thus making PpCalS5 a suspect gene involved in moss spore exine development.

PMID- 19155220
TI  - Ectomycorrhizal Inocybe species associate with the mycoheterotrophic orchid
      Epipogium aphyllum but not its asexual propagules.
AB  - BACKGROUND AND AIMS: Epipogium aphyllum is a Eurasian achlorophyllous,
      mycoheterotrophic forest orchid. Due to its rarity, it is often protected, and
      its biology is poorly known. The identity and pattern of colonization of fungal
      associates providing carbon to this orchid have not been studied previously.
      METHODS: Using samples from 34 individuals from 18 populations in Japan, Russia
      and France, the following were investigated: (a) colonization patterns of fungal
      associates of E. aphyllum by microscopy; (b) their identity by PCR amplification
      of nuclear ribosomal ITS carried out on rhizome fragments and hyphal pelotons.
      RESULTS AND CONCLUSIONS: Microscopic investigations revealed that thick rhizomes
      were densely colonized by fungi bearing clamp-connections and dolipores, i.e.
      basidiomycetes. Molecular analysis identified Inocybe species as exclusive
      symbionts of 75 % of the plants investigated and, more rarely, other
      basidiomycetes (Hebeloma, Xerocomus, Lactarius, Thelephora species).
      Additionally, ascomycetes, probably endophytes or parasites, were sometimes
      present. Although E. aphyllum associates with diverse species from Inocybe
      subgenera Mallocybe and Inocybe sensu stricto, no evidence for cryptic speciation
      in E. aphyllum was found. Since basidiomycetes colonizing the orchid are
      ectomycorrhizal, surrounding trees are probably the ultimate carbon source.
      Accordingly, in one population, ectomycorrhizae sampled around an individual
      orchid revealed the same fungus on 11.2 % of tree roots investigated. Conversely,
      long, thin stolons bearing bulbils indicated active asexual multiplication, but
      these propagules were not colonized by fungi. These findings are discussed in the
      framework of ecology and evolution of mycoheterotrophy.

PMID- 19155221
TI  - Causes of decreased photosynthetic rate and metabolic capacity in water-deficient
      leaf cells: a critical evaluation of mechanisms and integration of processes.
AB  - BACKGROUND: Water deficit (WD) decreases photosynthetic rate (A) via decreased
      stomatal conductance to CO(2) (g(s)) and photosynthetic metabolic potential
      (A(pot)). The relative importance of g(s) and A(pot), and how they are affected
      by WD, are reviewed with respect to light intensity and to experimental
      approaches. SCOPE AND CONCLUSIONS: With progressive WD, A decreases as g(s)
      falls. Under low light during growth and WD, A is stimulated by elevated CO(2),
      showing that metabolism (A(pot)) is not impaired, but at high light A is not
      stimulated, showing inhibition. At a given intercellular CO(2) concentration
      (C(i)) A decreases, showing impaired metabolism (A(pot)). The C(i) and probably
      chloroplast CO(2) concentration (C(c)), decreases and then increases, together
      with the equilibrium CO(2) concentration, with greater WD. Estimation of C(c) and
      internal (mesophyll) conductance (g(i)) is considered uncertain. Photosystem
      activity is unaffected until very severe WD, maintaining electron (e(-))
      transport (ET) and reductant content. Low A, together with photorespiration (PR),
      which is maintained or decreased, provides a smaller sink for e(-)(,) causing
      over-energization of energy transduction. Despite increased non-photochemical
      quenching (NPQ), excess energy and e(-) result in generation of reactive oxygen
      species (ROS). Evidence is considered that ROS damages ATP synthase so that ATP
      content decreases progressively with WD. Decreased ATP limits RuBP production by
      the Calvin cycle and thus A(pot). Rubisco activity is unlikely to determine
      A(pot). Sucrose synthesis is limited by lack of substrate and impaired enzyme
      regulation. With WD, PR decreases relative to light respiration (R(L)), and
      mitochondria consume reductant and synthesise ATP. With progressing WD at low A,
      R(L) increases C(i) and C(c). This review emphasises the effects of light
      intensity, considers techniques, and develops a qualitative model of
      photosynthetic metabolism under WD that explains many observations: testable
      hypotheses are suggested.

PMID- 19155222
TI  - Analysis of apoptosis and expression of genes related to apoptosis in cultures of
      follicles derived from vitrified and non-vitrified ovaries.
AB  - The aim of this study was to evaluate the incidence of apoptosis after in vitro
      culture of isolated follicles derived from vitrified and non-vitrified ovaries.
      Mouse ovaries were vitrified and their pre-antral follicles were mechanically
      isolated and cultured for 10 days. Growth and survival rates of the follicles
      were assessed during the culture period and the ultrastructure of the follicles
      was studied. The expression of p53, Bcl-2, Bax, Fas, FasL and survivin were
      analyzed by real-time RT-PCR in different follicular developmental stages. The
      percentages of apoptotic and necrotic cells were determined using a fluorescein
      activated cell sorting (FACS) technique. There were no differences between the
      growth and survival rates of follicles in the vitrified and non-vitrified groups.
      All of the evaluated genes were expressed in the pre-antral, large pre-antral and
      antral follicles in both groups, except Fas mRNA, which was not expressed in the
      pre-antral follicles. The expression of p53, Bcl2, Bax and FasL mRNA was similar
      in vitrified and non-vitrified groups; however, Fas mRNAs were more strongly
      expressed in the antral follicles of the vitrified group than of the control
      group (P < 0.05). The expression of survivin 140 was lower in the antral
      follicles of the vitrified group than of the control group (P < 0.05). FACS
      analysis showed that the percentage of intact cells was lower in the vitrified
      group than in the non-vitrified group (P < 0.05). This study demonstrated no
      signs of apoptosis ultrastructurally in cultured follicles; however,
      vitrification was shown to affect the expression of some genes related to
      apoptosis.

PMID- 19155223
TI  - Does surgery for primary non-small cell lung cancer and cerebral metastasis have
      any impact on survival?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was whether surgical resection of non-small cell
      lung cancer (NSCLC) with cerebral metastasis prolongs survival. Altogether 153
      relevant papers were identified using the below mentioned search, 11 papers
      represented the best evidence to answer the question. The author, date, journal,
      country of publication, study type, patient group studied, relevant outcomes,
      results and study weaknesses were tabulated. A vast majority of patients with
      synchronous presentation underwent cerebral metastasectomy prior to lung
      resection which led to a rapid regression of neurological symptoms. In these
      studies, the median survival for the curative intent groups (bifocal therapy+/
      adjuvant treatment) ranged from 19 to 27 months (mean 23.12+/-3.3 months) and at
      1, 2 and 5 years from 56% to 69% (mean=63.9+/-5.6%), 28% to 54% (mean=38.7+/-11%)
      and 11% to 24% (mean=18+/-5.7%), respectively. In comparison, the median and 1
      year survival of the palliative groups were 7.1-12.9 months (mean=10.3+/-2.9
      months) and 33-39.7% (mean=35.3+/-3.8%), respectively. We conclude that in the
      absence of mediastinal lymph node involvement, surgical resection of NSCLC with
      complete resection of the brain metastasis improves prognosis. Further,
      adenocarcinoma, low CEA levels at presentation, response to preoperative
      chemotherapy before focal treatment and a high Karnofsky performance score (KPS)
      may have a positive prognostic value.

PMID- 19155224
TI  - Right ventricular mural endocarditis presenting as an isolated apical mass in a
      non-addict patient with congenital deafness and aphasia.
AB  - Right heart infective endocarditis presenting as an isolated apical mural mass is
      an extremely uncommon finding. A 24-year-old woman with congenital deafness and
      aphasia was admitted with recurrent attacks of fever and lobar pneumonia. Her
      past medical history was significant for an open operation for left
      nephrolithiasis five months before admission. She had no history of congenital
      heart defect, intravenous drug use or central venous line insertion. Diagnostic
      workup revealed a large pedunculated solid mass attached to the apex of the right
      ventricle and multiple septic foci in both lungs. Repeated blood cultures were
      negative. In spite of aggressive antibiotic therapy, she had progressively
      worsening respiratory distress. She was successfully operated for the mass and
      the pathologic findings were consistent with endocarditis. To our knowledge, the
      anatomical location of the mural endocarditis (apex of right ventricle) is a
      pretty uncommon condition.

PMID- 19155225
TI  - Efficacy of telavancin against glycopeptide-intermediate Staphylococcus aureus in
      the neutropenic mouse bacteraemia model.
AB  - OBJECTIVES: The aim of the study was to compare the efficacies of telavancin and
      vancomycin against glycopeptide-intermediate Staphylococcus aureus (GISA) and
      heterogeneous vancomycin-intermediate S. aureus (hVISA) in a neutropenic murine
      bacteraemia model. METHODS: Immunocompromised mice (female non-Swiss albino, 18
      30 g) were inoculated intraperitoneally with 10(7) cfu/mL of GISA (strain HIP
      5836 or Mu50) or hVISA (strain Mu3). Infected mice received a subcutaneous dose
      of telavancin (40 mg/kg) or vancomycin (110 mg/kg) at 4 and 16 h post
      inoculation. Control animals received a subcutaneous dose of vehicle at 4 h post
      inoculation only. Blood and spleen bacterial titres were quantified in drug
      treated mice at 16, 28 and 52 h post-inoculation. RESULTS: Telavancin was 8-fold
      more potent than vancomycin against HIP-5836 (MIC 1 versus 8 mg/L), 16-fold more
      potent against Mu50 (MIC 0.5 versus 8 mg/L) and 8-fold more potent against Mu3
      (MIC 0.25 versus 2 mg/L). Telavancin produced significant (P < 0.05) and
      sustained reductions in blood and spleen titres from pre-treatment levels in mice
      infected with HIP-5836, Mu50 or Mu3. Vancomycin lowered blood and spleen HIP-5836
      counts transiently, but did not lower blood or spleen Mu50 or Mu3 counts
      significantly at any timepoint. Reductions in blood and spleen HIP-5836 and Mu3
      titres and in spleen Mu50 titres at 52 h post-inoculation were significantly
      greater with telavancin than vancomycin (P < 0.05). CONCLUSIONS: Telavancin was
      more efficacious than vancomycin in clearing infections caused by GISA strains
      HIP-5836 and Mu50 and hVISA strain Mu3 in a neutropenic mouse bacteraemia model.
      Further evaluation of telavancin for GISA and hVISA bacteraemia is warranted.

PMID- 19155226
TI  - SXT-related integrating conjugative element and IncC plasmids in Vibrio cholerae
      O1 strains in Eastern Africa.
AB  - OBJECTIVES: The objective of this study was to investigate the extent of
      resistance patterns and associated mobile genetic elements in epidemic V.
      cholerae O1 El Tor strains isolated from Eastern Africa in the late 1990s.
      METHODS: Self-transmissible genetic elements and associated clusters of genes
      encoding resistance were detected by conjugation experiments. Detection of SXT
      related integrating conjugative elements (ICEs) and associated antibiotic
      resistance genes was performed by PCR to amplify the SXT element-integrase gene
      (int), right SXT element-chromosome junction (attP-prfC) and genes conferring
      resistance to chloramphenicol (floR), sulfamethoxazole (sulII), streptomycin
      (strA) and trimethoprim (dfrA1). Genomic relatedness was established by random
      amplified polymorphic DNA patterns. RESULTS: Of 224 strains analysed, 200
      isolates exhibited resistance to four or more antimicrobials. An IncC plasmid,
      encoding resistance to ampicillin, chloramphenicol, streptomycin,
      sulfamethoxazole and trimethoprim, conferred multidrug resistance to 113 strains
      isolated from Somalia and Ethiopia, whereas an SXT-related ICE, encoding
      resistance to chloramphenicol, streptomycin, sulfamethoxazole and trimethoprim,
      conferred multidrug resistance to 74 strains isolated from Sudan, Kenya and
      Tanzania. CONCLUSIONS: This study has shown the spread of SXT-related ICEs among
      V. cholerae O1 African isolates. It has also highlighted the role of two distinct
      genetic elements in conferring multiple resistance to the two distinct groups of
      V. cholerae O1 strains that, in the late 1990s, spread through Eastern Africa, a
      critical geographic region for the persistence and transmission of cholera to the
      entire continent.

PMID- 19155227
TI  - Characterization of blaKPC-containing Klebsiella pneumoniae isolates detected in
      different institutions in the Eastern USA.
AB  - BACKGROUND: The emergence of bla(KPC)-containing Klebsiella pneumoniae (KPC-Kp)
      isolates is attracting significant attention. Outbreaks in the Eastern USA have
      created serious treatment and infection control problems. A comparative multi
      institutional analysis of these strains has not yet been performed. METHODS: We
      analysed 42 KPC-Kp recovered during 2006-07 from five institutions located in the
      Eastern USA. Antimicrobial susceptibility tests, analytical isoelectric focusing
      (aIEF), PCR and sequencing of bla genes, PFGE and rep-PCR were performed. Results
      By in vitro testing, KPC-Kp isolates were highly resistant to all non-carbapenem
      beta-lactams (MIC(90)s >or= 128 mg/L). Among carbapenems, MIC(50/90)s were 4/64
      mg/L for imipenem and meropenem, 4/32 mg/L for doripenem and 8/128 for ertapenem.
      Combinations of clavulanate or tazobactam with a carbapenem or cefepime did not
      significantly lower the MIC values. Genetic analysis revealed that the isolates
      possessed the following bla genes: bla(KPC-2) (59.5%), bla(KPC-3) (40.5%),
      bla(TEM-1) (90.5%), bla(SHV-11) (95.2%) and bla(SHV-12) (50.0%). aIEF of crude
      beta-lactamase extracts from these strains supported our findings, showing beta
      lactamases at pIs of 5.4, 7.6 and 8.2. The mean number of beta-lactamases was 3.5
      (range 3-5). PFGE demonstrated that 32 (76.2%) isolates were clonally related
      (type A). Type A KPC-Kp isolates (20 bla(KPC-2) and 12 bla(KPC-3)) were detected
      in each of the five institutions. rep-PCR showed patterns consistent with PFGE.
      CONCLUSIONS: We demonstrated the complex beta-lactamase background of KPC-Kp
      isolates that are emerging in multiple centres in the Eastern USA. The prevalence
      of a single dominant clone suggests that interstate transmission has occurred.

PMID- 19155228
TI  - A simple disc diffusion method for detecting AmpC and extended-spectrum beta
      lactamases in clinical isolates of Enterobacteriaceae.
AB  - BACKGROUND: We sought to determine whether extended-spectrum beta-lactamases
      (ESBLs) and AmpC beta-lactamases (derepressed and inducible), alone and in
      combination, could be detected in unidentified members of the Enterobacteriaceae
      using a simple, overnight disc diffusion test. METHODS: The genetic basis of
      antibiotic resistance in cephalosporin-resistant wild-type (n = 140) and culture
      collection (n = 140) isolates of Enterobacteriaceae was determined using PCR. A
      scheme for detecting these resistance mechanisms phenotypically was devised using
      five antibiotic discs: cefpodoxime +/- clavulanate; cefepime +/- clavulanate and
      cefoxitin. RESULTS AND CONCLUSIONS: AmpC beta-lactamases (derepressed and
      inducible) and ESBLs, alone and in combination, could reliably be detected using
      a disc diffusion method. ESBLs alone could be detected on the basis of a
      difference of >5 mm between cefpodoxime/clavulanate and cefpodoxime (10 microg)
      discs. ESBLs, in the presence of AmpC beta-lactamases, could be detected using a
      difference of >5 mm between cefepime/clavulanate and cefepime (30 microg) discs.
      AmpC beta-lactamases could be detected using a difference of >14 mm between
      cefepime/clavulanate and cefpodoxime/clavulanate discs. Inducible AmpC beta
      lactamases could be discerned by observing the blunting of the cefpodoxime or
      cefpodoxime/clavulanate zones in proximity to cefoxitin (30 microg) discs.

PMID- 19155229
TI  - Biochemical and neurotransmitter changes implicated in alcohol-induced brain
      damage in chronic or 'binge drinking' alcohol abuse.
AB  - The brain damage, which occurs after either chronic alcoholization or binge
      drinking regimes, shows distinct biochemical and neurotransmitter differences. An
      excessive amount of glutamate is released into specific brain regions during
      binge drinking (in excess of 4- to 5-fold of the normal basal concentration) that
      is not evident during periods of excessive alcohol consumption in chronic alcohol
      abusers. Increases in glutamate release are only observed during the initial
      stages of withdrawal from chronic alcoholism ( approximately 2- to 3-fold) due to
      alterations in the sensitivities of the NMDA receptors. Such changes in either
      density or sensitivity of these receptors are reported to be unaltered by binge
      drinking. When such excesses of glutamate are released in these two different
      models of alcohol abuse, a wide range of biochemical changes occur, mediated in
      part by increased fluxes of calcium ions and/or activation of various G-protein
      associated signalling pathways. Cellular studies of alveolar macrophages isolated
      from these two animal models of alcohol abuse showed enhanced (binge drinking) or
      reduced (chronic alcoholization) lipopolysaccharide (LPS)-stimulated NO release.
      Such studies could suggest that neuroadaptation occurs with the development of
      tolerance to alcohol's effects in both neurotransmitter function and cellular
      processes during chronic alcoholization that delay the occurrence of brain
      damage. In contrast, 'binge drinking' induces immediate and toxic effects and
      there is no evidence of an increased preference for alcohol as seen after
      withdrawal from chronic alcoholization.

PMID- 19155230
TI  - Therapeutic hypothermia can be induced and maintained using either commercial
      water bottles or a "phase changing material" mattress in a newborn piglet model.
AB  - BACKGROUND: Therapeutic hypothermia, a safe and effective treatment for neonatal
      encephalopathy in an intensive care setting, is not available in low-resource
      settings. Aims/ METHODS: To assess two low-tech, low-cost cooling devices for use
      in low-resource settings: (i) commercially available water bottles filled with
      tepid water (25 degrees C); (ii) a mattress made of phase changing material (PCM)
      with a melting point of 32 degrees C (PCM works as a heat buffer at this
      temperature). Eleven anaesthetised newborn piglets were studied following
      transient hypoxia-ischaemia. The cooling device was applied 2-26 h after hypoxia
      ischaemia with a target rectal temperature (T(rectal)) of 33-34 degrees C.
      T(rectal) undershoot was adjusted using cotton blankets; the cooling device was
      renewed when T(rectal) rose above 35 degrees C. T(rectal) data during cooling
      were dichotomised (within or without target) to assess: (a) the total period
      within the target T(rectal) range; (b) the stability and fluctuation of T(rectal)
      during cooling. RESULTS: Therapeutic hypothermia was achieved with both water
      bottles (n = 5) and the PCM mattress (n = 6). The mean (SD) time to reach target
      T(rectal) was 1.8 (0.5) h with water bottles and 1.9 (0.3) h with PCM. PCM
      cooling led to a longer period within the target T(rectal) range (p<0.01) and
      more stable cooling (p<0.05). Water bottle cooling required device renewal (in
      four out of five piglets). CONCLUSION: Simple, low-tech cooling devices can
      induce and maintain therapeutic hypothermia effectively in a porcine model of
      neonatal encephalopathy, although frequent fine tuning by adjusting the number of
      blankets insulating the piglet was required to maintain a stable temperature. PCM
      may induce more stable cooling compared with water bottles.

PMID- 19155231
TI  - Problem behaviours and parenting in preschool children with cystic fibrosis.
AB  - BACKGROUND: Problems with sleep, eating and adherence to therapy may adversely
      affect health outcomes in children with cystic fibrosis (CF). Data on the
      prevalence of such problems, associated parenting styles and caregiver mental
      health are limited. AIMS: To determine: (a) the prevalence of sleep, mealtime,
      therapy adherence and externalising and internalising behavioural problems in
      preschool children with CF; (b) the prevalence of caregiver mental health
      problems and poor sleep quality; and (c) associations between child behavioural
      problems and parenting styles. METHODS: This was a cross sectional survey of
      caregivers of children aged 6 months to 5 years attending CF outpatient clinics
      at Royal Children's Hospital (Melbourne), Monash Medical Centre (Melbourne) and
      Sydney Children's Hospital. Main outcome measures were child externalising and
      internalising behaviours, sleep, eating and adherence with therapy; the predictor
      was parenting styles (harsh, inconsistent, overprotective). RESULTS: 117 of 139
      families participated. Problems were common with child sleep (small PROBLEM:
      31.6%; moderate/large problem: 21.9%), eating (32.4%) and adherence with
      physiotherapy (50.4%). Compared to normative data, sleep and mealtime problems
      were more prevalent. Caregivers reported high rates of symptoms indicating
      depression (33.3%), anxiety (16.4%) and stress (34.2%). Harsh parenting was
      associated with internalising behaviours (adjusted OR 3.9, 95% CI 1.16 to 13.17,
      p = 0.03). CONCLUSIONS: Problems with sleeping, eating and physiotherapy
      adherence were common in preschool children with CF. Caregivers reported high
      rates of symptoms indicative of mental health problems. Harsh parenting was
      associated with internalising problems. An intervention targeting child problem
      behaviours and parental mental health would be appropriate for CF families.

PMID- 19155232
TI  - Immunohistochemical evidence of local production of catecholamines in cells of
      the muscle origins at the lateral and medial humeral epicondyles: of importance
      for the development of tennis and golfer's elbow?
AB  - BACKGROUND: Tennis elbow (TE) is a painful condition affecting the common
      extensor origin at the lateral humeral epicondyle. Colour Doppler examination has
      shown increased blood flow at this site and the sensory, and sympathetic
      innervation patterns have been delineated. However, it is not known whether there
      is local production of catecholamines and/or acetylcholine in this tissue, which
      is the case in patellar and Achilles tendinopathies. OBJECTIVE: To investigate
      the possible presence of local production of catecholamines and acetylcholine in
      non-neuronal cells (fibroblasts) in connective tissue at the muscle origin at the
      lateral humeral epicondyle in patients with TE. DESIGN: Immunohistochemical
      studies were performed on biopsies taken from the extensor origin in patients
      with TE and in pain-free controls. For reference purpose, biopsies from the
      flexor origin in patients with golfer's elbow (GE) were also studied. PATIENTS:
      Seven patients with TE and four patients with GE. Six healthy asymptomatic
      individuals served as controls. METHOD: Immunohistochemistry, using antibodies
      detecting synthesising enzymes for catecholamines (tyrosine hydroxylase; TH) and
      acetylcholine (choline acetyltransferase; ChAT). RESULTS: TH-like
      immunohistochemical reactions were seen in fibroblasts in four of the seven
      patients with TE and two of the four patients with GE. No such reactions were
      detected in controls (0/6). No ChAT reactions were seen in any of the
      investigated specimens. CONCLUSIONS: There is evidence of local, non-neuronal
      production of catecholamines, but not acetylcholine, in fibroblasts in the tissue
      at the muscle origin at the lateral and medial epicondyles in patients with TE
      and GE, respectively, which might have an influence on blood vessel regulation
      and pain mechanisms in these conditions.

PMID- 19155233
TI  - Safety of biological therapies following rituximab treatment in rheumatoid
      arthritis patients.
AB  - OBJECTIVE: To assess the safety of biological disease-modifying antirheumatic
      drugs (DMARD) in rheumatoid arthritis (RA) patients following rituximab. METHODS:
      RA patients who participated in an international rituximab clinical trial
      programme were included. Patients who had received one or more rituximab courses
      and entered safety follow-up (SFU) were permitted additional biological DMARD.
      Serious infection events (SIE) were collected. RESULTS: Of 185 of 2578 patients
      who entered SFU and received another biological DMARD, 88.6% had peripheral B
      cell depletion at the time of initiation of another biological agent. Thirteen
      SIE (6.99 events/100 patient-years) occurred following rituximab but before
      another biological DMARD and 10 SIE (5.49 events/100 patient-years) occurred
      following another biological DMARD. SIE were of typical type and severity for RA
      patients. 153 had received one or more tumour necrosis factor inhibitor(s). No
      fatal or opportunistic infections occurred. CONCLUSIONS: In this analysis,
      treatment with biological DMARD after rituximab was not associated with an
      increased serious infection rate. Sample size with limited follow-up restricts
      definitive conclusions.

PMID- 19155234
TI  - DAS-driven therapy versus routine care in patients with recent-onset active
      rheumatoid arthritis.
AB  - OBJECTIVES: To compare the efficacy of Disease Activity Score (DAS)-driven
      therapy and routine care in patients with recent-onset rheumatoid arthritis.
      METHODS: Patients with recent-onset rheumatoid arthritis receiving traditional
      antirheumatic therapy from either the BeSt study, a randomised controlled trial
      comparing different treatment strategies (group A), or two Early Arthritis
      Clinics (group B) were included. In group A, systematic DAS-driven treatment
      adjustments aimed to achieve low disease activity (DAS < or =2.4). In group B,
      treatment was left to the discretion of the treating doctor. Functional ability
      (Health Assessment Questionnaire (HAQ)), Disease Activity Score in 28 joints
      (DAS28) and Sharp/van der Heijde radiographic score (SHS) were evaluated.
      RESULTS: At baseline, patients in group A (n = 234) and group B (n = 201) had
      comparable demographic characteristics and a mean HAQ of 1.4. Group A had a
      longer median disease duration than group B (0.5 vs 0.4 years, p = 0.016), a
      higher mean DAS28 (6.1 vs 5.7, p<0.001), more rheumatoid factor-positive patients
      (66% vs 42%, p<0.001) and more patients with erosions (71% vs 53%, p<0.001).
      After 1 year, the HAQ improvement was 0.7 vs 0.5 (p = 0.029), and the percentage
      in remission (DAS28 <2.6) 31% vs 18% (p<0.005) in groups A and B, respectively.
      In group A, the median SHS progression was 2.0 (expected progression 7.0), in
      group B, the SHS progression was 1.0 (expected progression 4.4). CONCLUSIONS: In
      patients with recent-onset rheumatoid arthritis receiving traditional treatment,
      systematic DAS-driven therapy results in significantly better clinical
      improvement and possibly improves the suppression of joint damage progression.

PMID- 19155235
TI  - The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose
      and high-dose intravenous cyclophosphamide.
AB  - OBJECTIVE: To update the follow-up of the Euro-Lupus Nephritis Trial (ELNT), a
      randomised prospective trial comparing low-dose (LD) and high-dose (HD)
      intravenous (IV) cyclophosphamide (CY) followed by azathioprine (AZA) as
      treatment for proliferative lupus nephritis. PATIENTS AND METHODS: Data for
      survival and kidney function were prospectively collected during a 10-year period
      for the 90 patients randomised in the ELNT, except in 6 lost to follow-up.
      RESULTS: Death, sustained doubling of serum creatinine and end-stage renal
      disease rates did not differ between the LD and HD group (5/44 (11%) vs 2/46
      (4%), 6/44 (14%) vs 5/46 (11%) and 2/44 (5%) vs 4/46 (9%), respectively) nor did
      mean serum creatinine, 24 h proteinuria and damage score at last follow-up. Most
      patients in both groups were still treated with glucocorticoids, other
      immunosuppressant agents and blood pressure lowering drugs. After 10 years of
      follow-up, the positive predictive value for a good outcome of an early drop in
      proteinuria in response to initial immunosuppressive therapy was confirmed.
      CONCLUSION: The data confirm that a LD IVCY regimen followed by AZA-the "Euro
      Lupus regimen"-achieves good clinical results in the very long term.

PMID- 19155236
TI  - Antenatal depression in socially high-risk women in Canada.
AB  - BACKGROUND: Antenatal depression is potentially deleterious to the mother and
      baby. Canadian Aboriginal women have an increased risk for living in poverty,
      family violence, and substance use; however, little is known about antenatal
      depression in this group. The aim of this study was to determine the prevalence
      and correlates of depression in socially high-risk, mostly Aboriginal pregnant
      women. METHODS: Women (Aboriginal and non-Aboriginal), in two prenatal outreach
      programmes were approached and depressive symptoms between the two groups were
      compared, using the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Sixty
      per cent (n = 402) of potential participants were recruited for the study. The
      prevalence of depression was 29.5% (n = 402). Depression was associated with a
      history of depression, mood swings, increased stressors, current smoker, and lack
      of social support. Aboriginal women were more likely to be depressed, but this
      was not significantly higher than non-Aboriginal women; however, they did
      experience significantly more self-harm thoughts. Exercise was a significant
      mediator for depression. CONCLUSION: The prevalence of antenatal depression
      confirms rates in other high-risk, ethnic minority groups of women. A previous
      history of depression and mood problems were associated with depression, thus
      prenatal care should include a careful mental health assessment. On a positive
      note, the present study suggests that exercise may mediate antenatal depression.

PMID- 19155237
TI  - Peritoneal stromal endometriosis: a detailed morphological analysis of a large
      series of cases of a common and under-recognised form of endometriosis.
AB  - AIMS: It is generally considered that an unequivocal histological diagnosis of
      endometriosis requires the presence of endometrioid-type glands and endometrioid
      type stroma. However, small nodules or plaques of endometrioid-type stroma
      without glands have been noticed by the authors in repeated peritoneal biopsies
      performed for suspected endometriosis. These are often, but not always,
      accompanied by typical endometriosis with glands. This form of endometriosis has
      been previously referred to as stromal or micronodular stromal endometriosis.
      However, there has been little reference to this condition in the literature.
      METHODS: In this study, there was a review of a large series (n = 274) of
      peritoneal biopsies with a diagnosis of endometriosis with a view to ascertaining
      the frequency of stromal endometriosis. RESULTS: Stromal endometriosis,
      characterised histologically by small microscopic nodules or plaques of
      endometrioid-type stroma, sometimes with a whorled pattern and prominent
      vascularity and erythrocyte extravasation, was identified in 44.9% of the
      biopsies. In 6.6% of the biopsies, stromal endometriosis occurred without typical
      endometriosis. The foci of stromal endometriosis usually had a superficial
      location just beneath the mesothelial surface or protruding above this.
      Associated histological features present in some cases included reactive
      mesothelial proliferation, inflammation, giant cell or granuloma formation,
      haemosiderin pigment deposition, microcalcification and decidualisation and
      myxoid change. CONCLUSIONS: Stromal endometriosis, usually in the form of
      superficial nodules or plaques, is a relatively common form of endometriosis
      which typically occurs in association with typical endometriosis but occasionally
      on its own. Pathologists should be aware of the existence of this form of
      endometriosis, the morphological features of which may be subtle. The typical
      location, intimately associated with surface mesothelium, may suggest that
      stromal endometriosis derives from mesothelial or submesothelial cells via a
      metaplastic process.

PMID- 19155238
TI  - Drug-induced cutaneous pathology.
AB  - Drug-induced cutaneous rashes, whether confined to the skin or part of a systemic
      disease, are characterised by a spectrum of inflammatory disease patterns that
      include perivascular dermatitis, nodular and diffuse dermatitis, vesiculobullous
      lesions, pustular eruptions, sclerodermoid reactions, vasculitis,
      folliculitis/perifolliculitis and panniculitis. While a single drug can elicit a
      range of reaction patterns, no reaction pattern is specific for a particular
      drug. Although the temporal link between initiation of drug therapy and the onset
      of the drug rash is critical to the diagnosis, drug reactions may also occur
      during the course of chronic drug ingestion. Clues to the drug-induced nature of
      the cutaneous eruption include the presence of overlapping histological reaction
      patterns and incongruent clinical and histopathological features. While
      eosinophils are an important tell-tale sign of a drug-induced reaction, they may
      also be conspicuous in skin rashes devoid of a drug association. Furthermore,
      eosinophils may be sparse or absent in some drug exanthems. Heightened awareness
      of the mimicry of a wide spectrum of cutaneous pathology by an ever-increasing
      range of therapeutic agents is pivotal to the diagnosis of drug-induced skin
      pathology.

PMID- 19155239
TI  - Is histological diagnosis of primary liver carcinomas with fibrous stroma
      reproducible among experts?
AB  - AIMS: In the era of targeted therapeutics, histological typing of hepatobiliary
      carcinomas has major clinical implications. Little is known about the
      reproducibility of the pathological diagnosis of primary liver carcinomas.
      Therefore, this study aimed to evaluate the worldwide variation in the
      pathological expert diagnoses of primary liver carcinomas with fibrous stroma in
      patients who did not have cirrhosis. METHODS: A single set of slides was selected
      from 25 tumours, and this set was reviewed independently by 12 pathologists who
      have worldwide expertise in liver tumours. Reproducibility of the diagnoses was
      evaluated by Light's kappa, and diagnoses were clustered by multidimensional
      scaling. Immunohistochemistry was performed after histological review. RESULTS:
      The interobserver reproducibility for diagnosis of hepatocellular carcinoma
      subtypes and cholangiocarcinomas was poor (kappa 0.23-0.52), even when the
      experts considered that the diagnosis required no additional stains or clinical
      information. Interestingly, multidimensional scaling revealed three main clusters
      of tumours: hepatocellular carcinoma with no other specifications (n = 13),
      fibrolamellar hepatocellular carcinoma (n = 3) and cholangiocarcinoma (n = 9).
      Using immunohistochemistry, these histological clusters correlated with
      expression of anti-hepatocyte and anti-cytokeratin 19 (p<0.001). CONCLUSIONS: The
      results demonstrate the poor reproducibility among experts of the pathological
      diagnosis of primary liver carcinomas with fibrous stroma in patients who did not
      have cirrhosis, and highlight that the systematic use of immunohistochemistry may
      improve the diagnostic accuracy.

PMID- 19155240
TI  - Assessment of a real-time PCR test to diagnose syphilis from diverse biological
      samples.
AB  - OBJECTIVES: To investigate the contribution of a real-time PCR assay for the
      detection of Treponema pallidum in various biological specimens with the
      secondary objective of comparing its value according to HIV status. METHODS:
      Prospective cohort of incident syphilis cases from three Swiss hospitals (Geneva
      and Bern University Hospitals, Outpatient Clinic for Dermatology of Triemli,
      Zurich) diagnosed between January 2006 and September 2008. A case-control study
      was nested into the cohort. Biological specimens (blood, lesion swab or urine)
      were taken at diagnosis (as clinical information) and analysed by real-time PCR
      using the T pallidum 47 kDa gene. RESULTS: 126 specimens were collected from 74
      patients with primary (n = 26), secondary (n = 40) and latent (n = 8) syphilis.
      Among primary syphilis, sensitivity was 80% in lesion swabs, 28% in whole blood,
      55% in serum and 29% in urine, whereas among secondary syphilis, it was 20%, 36%,
      47% and 44%, respectively. Among secondary syphilis, plasma and cerebrospinal
      fluid were also tested and provided a sensitivity of 100% and 50%, respectively.
      The global sensitivity of T pallidum by PCR (irrespective of the compartment
      tested) was 65% during primary, 53% during secondary and null during latent
      syphilis. No difference regarding serology or PCR results was observed among HIV
      infected patients. Specificity was 100%. CONCLUSIONS: Syphilis PCR provides
      better sensitivity in lesion swabs from primary syphilis and displays only
      moderate sensitivity in blood from primary and secondary syphilis. HIV status did
      not modify the internal validity of PCR for the diagnosis of primary or secondary
      syphilis.

PMID- 19155241
TI  - Testing commercial sex workers for chlamydia and gonorrhoea on outreach.
AB  - To assess the feasibility of testing indoor commercial sex workers (CSW) for
      Chlamydia trachomatis and Neisseria gonorrhoeae in an outreach setting. All CSW
      seen on outreach over a 6-week period were offered self-taken vulval swabs for
      chlamydia and gonorrhoea testing. Feasibility was assessed by all the outreach
      workers on a standardised proforma. Of the 93 women offered the service, 40
      accepted, of whom five (12%) had not previously accessed sexual health services.
      The majority of women declining the service had recently attended a sexual health
      clinic. Three cases of chlamydia and one of gonorrhoea were diagnosed. The cost
      per sexually transmitted infection (STI) was pound 392.50. Most of this group of
      women were knowledgeable about sexual health and were already having regular
      check-ups, but a significant minority did not know how to access STI care.
      Offering STI testing on outreach was feasible and cost effective.

PMID- 19155242
TI  - Neo-adjuvant treatment of rectal cancer with capecitabine and oxaliplatin in
      combination with radiotherapy: a phase II study.
AB  - BACKGROUND: Preoperative chemoradiation is now standard treatment for stages II
      III rectal cancer. Capecitabine (CAP) and oxaliplatin (OX) are synergistic with
      radiotherapy (RT) and active in colorectal neoplasms. PATIENTS AND METHODS: Two
      cycles of CAP 825 mg/m(2) b.i.d. (days 1-14) and OX 50 mg/m(2) (days 1 and 8)
      every 3 weeks were given concomitantly with pelvic conformal RT (45 Gy). Patients
      with a > or =T3 and/or node-positive rectal tumour were eligible. The pathologic
      tumour response was defined according to the tumour regression grade (TRG) scale.
      RESULTS: Forty-six patients were enrolled. Gastrointestinal adverse events were
      mostly G1-G2; only two patients experienced G3 vomiting and diarrhoea and six
      patients had G1 peripheral neuropathy. Haematological toxicity was rare. G2
      proctitis and anal pain occurred in two patients. Pathological complete response
      (TRG1) was observed in nine patients (20.9%; 95% CI 8.7%-33.1%); TRG2 in 19
      patients (44.2%); TRG3 in 12 patients (27.9%); and TRG4 in three patients (7%).
      Overall, nine patients recurred: five with distant metastases, one with local
      recurrence, and three with both local recurrence and distant metastases.
      CONCLUSIONS: CAP-OX-RT as preoperative treatment for rectal cancer induces a
      remarkable rate of complete or near-complete pathologically documented response
      and is well tolerated.

PMID- 19155246
TI  - Statistical methods in pharmacoepidemiology: advances and challenges.

PMID- 19155247
TI  - Comments on "A hierarchical zero-inflated log-normal model for skewed responses".

PMID- 19155249
TI  - Prediction of fatal or near-fatal cardiac arrhythmia events in patients with
      depressed left ventricular function after an acute myocardial infarction.
AB  - AIMS: To determine whether risk stratification tests can predict serious
      arrhythmic events after acute myocardial infarction (AMI) in patients with
      reduced left ventricular ejection fraction (LVEF < or = 0.40). METHODS AND
      RESULTS: A total of 5869 consecutive patients were screened in 10 European
      centres, and 312 patients (age 65 +/- 11 years) with a mean LVEF of 31 +/- 6%
      were included in the study. Heart rate variability/turbulence, ambient
      arrhythmias, signal-averaged electrocardiogram (SAECG), T-wave alternans, and
      programmed electrical stimulation (PES) were performed 6 weeks after AMI. The
      primary endpoint was ECG-documented ventricular fibrillation or symptomatic
      sustained ventricular tachycardia (VT). To document these arrhythmic events, the
      patients received an implantable ECG loop-recorder. There were 25 primary
      endpoints (8.0%) during the follow-up of 2 years. The strongest predictors of
      primary endpoint were measures of heart rate variability, e.g. hazard ratio (HR)
      for reduced very-low frequency component (<5.7 ln ms(2)) adjusted for clinical
      variables was 7.0 (95% CI: 2.4-20.3, P < 0.001). Induction of sustained
      monomorphic VT during PES (adjusted HR = 4.8, 95% CI, 1.7-13.4, P = 0.003) also
      predicted the primary endpoint. CONCLUSION: Fatal or near-fatal arrhythmias can
      be predicted by many risk stratification methods, especially by heart rate
      variability, in patients with reduced LVEF after AMI.

PMID- 19155250
TI  - A meta-analysis of randomized controlled trials in pulmonary arterial
      hypertension.
AB  - AIMS: There is no cure for pulmonary arterial hypertension, but current approved
      treatment options include prostanoids, endothelin-receptor antagonists, and
      phosphodiesterase type-5 inhibitors. The effect on survival of these compounds
      has not been appropriately assessed in individual trials because of small sample
      size and short duration. We performed a meta-analysis of all randomized
      controlled trials with drugs published in this condition. METHODS AND RESULTS:
      Trials were searched in the Medline database from January 1990 to October 2008.
      The primary analysis included only studies with a placebo comparator arm, the
      sensitivity analysis also included studies comparing two active treatment arms.
      The main outcome measure was all-cause mortality. Twenty-one trials were included
      in the primary analysis (3140 patients) and two additional studies (59 patients)
      were included in the sensitivity analysis. Average duration of the trials was
      14.3 weeks. All-cause mortality rate in the control group was 3.8%. Active
      treatments were associated with a reduction in mortality of 43% (RR 0.57; 95% CI
      0.35-0.92; P = 0.023); the sensitivity analysis confirmed a reduction in
      mortality of 38% (RR 0.62; 95% CI 0.39-1.00; P = 0.048). CONCLUSION: The results
      of this meta-analysis suggest an improvement of survival in the patients treated
      with the targeted therapies approved for pulmonary arterial hypertension.

PMID- 19155255
TI  - Use of emergency oxygen in adults.

PMID- 19155256
TI  - Germany's organ procurement body wants powers to run donation process.

PMID- 19155257
TI  - Lack of funding prevents human-animal stem cell research in UK.

PMID- 19155258
TI  - Two thirds of US prisoners with chronic conditions in local jails do not get
      medical care, study shows.

PMID- 19155260
TI  - Eli Lilly pays record $1.4bn for promoting off-label use of olanzapine.

PMID- 19155261
TI  - European red tape holds back UK research, say academics.

PMID- 19155262
TI  - Recent advances in the microbiology of respiratory tract infection in cystic
      fibrosis.
AB  - INTRODUCTION: Infection is a major cause of morbidity and mortality in patients
      with cystic fibrosis (CF). Research on CF infection has highlighted differences
      from other respiratory infections--both in the range and the nature of the
      organisms--especially in chronic infection. This is a rapidly advancing field of
      microbiology and is bringing insights into the complexity and adaptations of
      bacteria causing chronic infection in the respiratory tract. AREAS OF AGREEMENT
      AND CONTROVERSY: The epidemiology of some infections in CF has changed, with
      reduction in spread of Burkholderia cenocepacia following patient segregation.
      Conversely, epidemic strains of Pseudomonas aeruginosa have emerged, which spread
      between patients; previously, most P. aeruginosa strains were patient-specific.
      Studies on hypermutators, quorum sensing, biofilm growth and the development of
      molecular identification have shed light on pathogenicity, microbial adaptation
      to the host and complexity of infection in CF. Non-tuberculous mycobacteria are
      emerging pathogens in CF; however, there is much to learn about pathogenicity and
      treatment of these infections. Species of aerobic and anaerobic bacteria, more
      commonly encountered in the upper tract, are found in significant numbers in CF
      sputum. The significance of this is however under debate. Finally, although the
      clinical relevance of conventional antibiotic susceptibility testing for chronic
      CF pathogens has been questioned, there are no clear alternatives. EMERGING AREAS
      FOR DEVELOPING RESEARCH: Much has been learnt about pathogenicity, evolution of
      CF pathogens and development of antibiotic resistance. The need is to focus on
      clinical relevance of these observations to improve diagnosis, prevention and
      treatment of CF infection.

PMID- 19155263
TI  - Nomograms for severity of aortic valve stenosis using peak aortic valve pressure
      gradient and left ventricular ejection fraction.
AB  - AIMS: Continuity equation to evaluate aortic valve area (AVA(CE)) is critically
      dependent on accurate measurement of left ventricular outflow tract diameter and
      velocity. To circumvent these limitations, the present study aimed to generate
      nomograms for a facilitated estimation of aortic valve area using peak aortic
      valve pressure gradient (DeltapAv) and left ventricular ejection fraction (LVEF).
      METHODS AND RESULTS: Two hundred and fifty-five subjects with non-invasively and
      invasively defined aortic valve stenosis (AS) formed the basis of this study.
      Basis of the nomograms was the correlation analysis between DeltapAv and AVA as
      estimated by AVA(CE) within different LVEF groups. LVEF differed from 65.6 +/-
      1.8% (Group I, LVEF > 60%) to 34.5 +/- 4.3% (Group IV, LVEF > or = 30%). DeltapAv
      and AVA varied from 85.6 +/- 19.5 mmHg and 0.69 +/- 0.16 cm2 in Group I to 58.5
      +/- 15.9 mmHg and 0.73 +/- 0.23 cm2 in Group IV (DeltapAv: P < 0.001). Mean
      AVA(CE) showed no significant difference between the groups. Correlation between
      DeltapAv and AVA(CE) was statistically significant with P < 0.001 in all
      subgroups (R2 between 0.72 and 0.76). Furthermore, a prospective estimation of
      AVA using the developed nomograms correlated very well with invasively determined
      AS using the Gorlin formula (R2 = 0.76, SEE = 0.21 cm2, bias 0.04 cm2).
      CONCLUSION: The present study has established and confirmed a solid, easy to use
      nomogram-based method to accurately quantify severe AS.

PMID- 19155264
TI  - Two-dimensional strain and strain rate imaging of the right ventricle in adult
      patients before and after percutaneous closure of atrial septal defects.
AB  - AIMS: Echocardiographic speckle tracking or two-dimensional (2D) strain analysis
      is a new tool to assess myocardial function. This prospective controlled study
      evaluates systolic right ventricular (RV) function by 2D strain in adult patients
      with atrial septal defect (ASD) before and 3 months after percutaneous closure.
      METHODS AND RESULTS: Assessment of global longitudinal strain (GLS), global
      longitudinal strain rate (GLSR), and regional peak systolic strain (PSS) of right
      ventricle was performed in 33 ASD patients. The data were compared with those
      from 34 age-matched adults with patent foramen ovale. Before percutaneous
      closure, mean GLS was significantly increased in comparison to control group, and
      significantly reduced after closure. Analysis of regional PSS showed significant
      decrease in the lateral apical, lateral mid, and septal apical segments. GLSR was
      not influenced by ASD closure. CONCLUSION: Two-dimensional strain appears to be
      helpful also for the assessment of RV function and its response to correction of
      volume overload.

PMID- 19155265
TI  - The influence of domain structures on the signal transduction of chimeric
      receptors derived from the erythropoietin receptor.
AB  - Although cytokine receptors regulate many cellular functions, contribution of
      receptor's domains and their conformation to signal transduction remains unclear.
      In this study, we designed a series of chimeric erythropoietin receptor (EpoR)
      variants encoding a haemagglutinin epitope-tagged anti-fluorescein single-chain
      Fv and different combinations of extracellular D1/D2 domain(s) of EpoR as the
      extracellular domain to allow the receptor to be activated by multiple ligands.
      Furthermore, one to four Ala residues were inserted at the intracellular
      juxtamembrane region of each chimeric receptor to modulate the conformation of
      the intracellular domain. When the chimeric receptors were expressed in Ba/F3
      cells, cell-surface expression levels of chimeric receptors without D2 domain
      were markedly lowered, suggesting a role of D2 domain for stabilizing the
      receptor. Furthermore, the ligand-dependent cell proliferation was strongly
      affected by extracellular domain structures and the number of inserted Ala
      residues. Moreover, the conformational change of chimeric receptors was induced
      by various ligands to detect the phosphorylation of JAK2, STAT5 and ERK2, whose
      activations are characteristics of EpoR signalling. Consequently, the
      phosphorylation pattern of these signal transducers was significantly influenced
      by ligands and receptor variants. These results indicate that signal transduction
      of EpoR is strongly affected by conformation of both extracellular and
      intracellular domains.

PMID- 19155266
TI  - Peroxiredoxin III-deficiency sensitizes macrophages to oxidative stress.
AB  - As a mitochondrial scavenger of reactive oxygen species (ROS), peroxiredoxin III
      (PrxIII) plays an important role in regulating intracellular ROS level. We
      previously found that PrxIII knockout (PrxIII(-/-)) mice were more sensitive than
      wild-type (PrxIII(+/+)) controls to intratracheal inoculation of
      lipopolysaccharide (LPS), but the precise mechanism remained to be obscure. In
      the present study, we detected the levels of ROS and tumour necrosis factor alpha
      (TNF-alpha) in mouse bone-marrow-derived macrophages. LPS stimulation induced
      transient increase of ROS production and augmentation of TNF-alpha accumulation
      in PrxIII(-/-) macrophages. In addition, we observed reduced viability and
      increased apoptosis in PrxIII(-/-) macrophages exposed to LPS. Our results
      provide direct evidence that PrxIII is necessary for macrophages to protect
      against LPS-induced oxidative stress.

PMID- 19155267
TI  - Serine racemase with catalytically active lysinoalanyl residue.
AB  - Serine racemase synthesizes d-serine, a physiological agonist of the NMDA
      receptor in mammalian brains. Schizosaccharomyces pombe produces serine racemase
      (spSR) that is highly similar to the brain enzyme. Our mass-spectrometric and X
      ray studies revealed that spSR is modified with its natural substrate serine.
      spSR remains partially active even though its essential Lys57 inherently forming
      a Schiff base with the coenzyme pyridoxal 5'-phosphate is converted to N(6)-(R-2
      amino-2-carboxyethyl)-l-lysyl (lysino-d-alanyl) residue. This indicates that the
      alpha-amino group of the d-alanyl moiety of the lysino-d-alanyl residue serves as
      a catalytic base in the same manner as the epsilon-amino group of Lys57 of the
      original spSR.

PMID- 19155268
TI  - Interactions between histidine and tryptophan residues in the BM2 proton channel
      from influenza B virus.
AB  - The BM2 protein of influenza B virus forms a transmembrane proton channel
      essential for the virus infection. We investigated the structure and mechanism of
      the BM2 proton channel by using a 31-mer peptide (BM2-TMP) representing the
      putative transmembrane domain of BM2, with special focus on His19, Trp23 and
      His27. Like the full-length protein, BM2-TMP formed a transmembrane proton
      channel activated at acidic pH with a midpoint of transition at pH 6.4 +/- 0.1.
      Mutation of His19 to Ala almost abolished the channel activity, whereas the His27
      to-Ala mutant retained partial activity. The proton selectivity of the channel
      was lost upon substitution of Phe for Trp23. Comparison of CD, fluorescence and
      Raman spectra measured for wild-type and mutated BM2-TMP at varied pH showed the
      pK(a) of the imidazole ring to be approximately 6.5 for His19 and approximately
      7.6 for His27. Analysis of the pH-dependent fluorescence and Raman intensities
      suggested the occurrence of cation-pi interaction between the protonated
      imidazole ring of His and the indole ring of Trp. The His19-Trp23 cation-pi
      interaction below pH 6.5 is likely to trigger the opening of the proton channel,
      whereas His27 is not essential but enhances the channel activity through
      interaction with Trp23, which constitutes the proton-selective gate.

PMID- 19155269
TI  - Inspection of the activator binding site for 4-alpha-glucanotransferase in
      porcine liver glycogen debranching enzyme with fluorogenic dextrins.
AB  - Recently, we found that alpha-, beta- and gamma-cyclodextrins accelerated the 4
      alpha-glucanotransferase action of porcine liver glycogen debranching enzyme
      (GDE) on Glcalpha1-4Glcalpha1-4Glcalpha1-4(Glcalpha1-4Glcalpha1-4Glcalpha1
      4Glcalpha1-6)Glcalpha1-4Glcalpha1-4Glcalpha1-4Glcalpha1-4GlcPA (B5/84), and
      proposed the presence of an activator binding site in the GDE molecule. In liver
      cells, the structures of alpha-glucans proximal to the site GDE acts are not
      cyclodextrins, but glycogen and its degradation products. To estimate the
      structural characteristics of intrinsic activators and to inspect the features of
      the activator binding site, we examined the effects of four fluorogenic dextrins,
      (Glcalpha1-6)(m)Glcalpha1-4(Glcalpha1-4)(n)GlcPA (B5/51, m = 1, n = 3; B6/61, m =
      1, n = 4; B7/71, m = 1, n = 5; G6PA, m = 0, n = 4), on the debranching of B5/84
      by porcine liver GDE. The GDE 4-alpha-glucanotransferase removed the maltotriosyl
      residue from the maltotetraosyl branch of B5/84, producing Glcalpha1-4Glcalpha1
      4Glcalpha1-4(Glcalpha1-6)Glcalpha1-4Glcalpha1-4Glcalpha1-4Glcalpha1-4GlcPA
      (B5/81). In the presence of G6PA, the removed maltotriosyl residue was
      transferred to G6PA to give Glcalpha1-4Glcalpha1-4Glcalpha1-4Glcalpha1-4Glcalpha1
      4Glcalpha1-4Glcalpha1-4Glcalpha1-4GlcPA (G9PA). In the absence of G6PA, the
      removed maltotriosyl residue was transferred to water. B7/71, B6/61 and B5/51 did
      not undergo any changes by the GDE, but they accelerated the action of the 4
      alpha-glucanotransferase in removing the maltotriosyl residue. Of the four
      fluorogenic dextrins examined, B6/61 most strongly accelerated the 4-alpha
      glucanotransferase action. The activator binding site is likely to be a space
      that accommodates the structure of Glcalpha1-6Glcalpha1-4Glcalpha1-4Glcalpha1
      4Glcalpha1-4Glc.

PMID- 19155270
TI  - Reduced expression of fukutin related protein in mice results in a model for
      fukutin related protein associated muscular dystrophies.
AB  - Mutations in fukutin related protein (FKRP) are responsible for a common group of
      muscular dystrophies ranging from adult onset limb girdle muscular dystrophies to
      severe congenital forms with associated structural brain involvement, including
      Muscle Eye Brain disease. A common feature of these disorders is the variable
      reduction in the glycosylation of skeletal muscle alpha-dystroglycan. In order to
      gain insight into the pathogenesis and clinical variability, we have generated
      two lines of mice, the first containing a missense mutation and a neomycin
      cassette, FKRP-Neo(Tyr307Asn) and the second containing the FKRP(Tyr307Asn)
      mutation alone. We have previously associated this missense mutation with a
      severe muscle-eye-brain phenotype in several families. Homozygote Fkrp
      Neo(Tyr307Asn) mice die soon after birth and show a reduction in the laminin
      binding epitope of alpha-dystroglycan in muscle, eye and brain, and have reduced
      levels of FKRP transcript. Homozygous Fkrp(Tyr307Asn) mice showed no discernible
      phenotype up to 6 months of age, contrary to the severe clinical course observed
      in patients with the same mutation. These results suggest the generation of a
      mouse model for FKRP related muscular dystrophy requires a knock-down rather than
      a knock-in strategy in order to give rise to a disease phenotype.

PMID- 19155271
TI  - A subcortical oscillatory network contributes to recovery of hand dexterity after
      spinal cord injury.
AB  - Recent studies have shown that after partial spinal-cord lesion at the mid
      cervical segment, the remaining pathways compensate for restoring finger
      dexterity; however, how they control hand/arm muscles has remained unclear. To
      elucidate the changes in dynamic properties of neural circuits connecting the
      motor cortex and hand/arm muscles, we investigated the cortico- and inter
      muscular couplings of activities throughout the recovery period after the spinal
      cord lesion. Activities of antagonist muscle pairs showed co-activation and
      oscillated coherently at frequencies of 30-46 Hz (gamma-band) by 1-month post
      lesion. Such gamma-band inter-muscular coupling was not observed pre-lesion, but
      emerged and was strengthened and distributed over a wide range of hand/arm
      muscles along with the recovery. Neither the beta-band (14-30 Hz) cortico
      muscular coupling observed pre-lesion nor a gamma-band oscillation was observed
      in the motor cortex post-lesion. We propose that a subcortical oscillator
      commonly recruits hand/arm muscles, via remaining pathways such as reticulospinal
      and/or propriospinal tracts, independent of cortical oscillation, and contributes
      to functional recovery.

PMID- 19155272
TI  - Detection of elevated levels of soluble alpha-synuclein oligomers in post-mortem
      brain extracts from patients with dementia with Lewy bodies.
AB  - A number of neurodegenerative diseases including Parkinson's disease, dementia
      with Lewy bodies (DLB) and multiple system atrophy are characterized by the
      formation and intraneuronal accumulation of fibrillar aggregates of alpha
      synuclein (alpha-syn) protein in affected brain regions. These and other findings
      suggest that the accumulation of alpha-syn in the brain plays an important role
      in the pathogenesis of these diseases. However, more recently it has been
      reported that early amyloid aggregates or 'soluble oligomers' are the pathogenic
      species that lead to neurodegeneration and neuronal cell death rather than the
      later 'mature fibrils'. In this study, we investigated the presence of alpha-syn
      oligomers in brain lysates prepared from frozen post-mortem brains of normal,
      Alzheimer's disease and DLB patients. The brain extracts were subjected to high
      speed centrifugation, to remove insoluble alpha-syn aggregates, followed by
      specific detection of soluble oligomers in the supernatants by employing FILA-1,
      an antibody that specifically binds to alpha-syn aggregates, but not to alpha-syn
      monomers, or to tau or beta-amyloid aggregates. Using this novel enzyme-linked
      immunosorbent assay (ELISA) method to quantify the amounts of alpha-syn oligomers
      in the brain extracts, our data clearly show an increase in the levels of soluble
      oligomers of alpha-syn in the DLB brains compared to those with Alzheimer's
      disease and the controls (P < 0.0001). Our findings provide strong evidence to
      support the contention that elevated soluble oligomers of alpha-syn are involved
      in the pathogenesis of DLB. Furthermore, these findings establish FILA-1 as a
      very sensitive tool for the detection of oligomeric forms of alpha-syn in human
      brain lysates.

PMID- 19155273
TI  - Filtrate of Phellinus linteus Broth Culture Reduces Infarct Size Significantly in
      a Rat Model of Permanent Focal Cerebral Ischemia.
AB  - Phellinus linteus, a natural growing mushroom, has been known to exhibit anti
      tumor, anti-inflammatory, anti-allergic and anti-oxidant effects. Aiming to
      exploit the neuroprotective effects of P. linteus, we evaluated its effects on
      infarct volume reduction in a rat model of focal cerebral ischemia. Male Sprague
      Dawley rats were subjected to right middle cerebral artery occlusion. Filtrate of
      P. linteus broth culture (various doses), fractionated filtrate (based on
      molecular weight) or control medium was administered intraperitoneally to rats
      before or after ischemia induction. Rats were killed at 24 h after the stroke
      surgery. Cortical and caudoputaminal infarct volumes were determined separately
      using an image analysis program following staining with 2,3,5
      triphenyltetrazolium chloride. Significant cortical infarct volume reductions
      were found in the pre-treatment groups (30 and 60 minutes before onset of
      cerebral ischemia) compared with the control group, showing dose dependence.
      Posttreatment (30 minutes after ischemic onset) also significantly reduced
      cortical infarct volume. Furthermore, the higher molecular weight (>=12 000)
      fraction of the culture filtrate was more effective compared with the lower
      molecular weight fraction. The present findings suggest that P. linteus may be a
      new promising approach for the treatment of focal cerebral ischemia, with the
      additional benefit of a wide therapeutic time window since significant infarct
      volume reduction is obtained by administration even after the ischemic event. Our
      finding that the higher molecular weight fraction of the P. linteus culture
      filtrate demonstrated more prominent effect may provide a clue to identify the
      neuroprotective substances and mechanisms.

PMID- 19155274
TI  - Specific recognition of a multiply phosphorylated motif in the DNA repair
      scaffold XRCC1 by the FHA domain of human PNK.
AB  - Short-patch repair of DNA single-strand breaks and gaps (SSB) is coordinated by
      XRCC1, a scaffold protein that recruits the DNA polymerase and DNA ligase
      required for filling and sealing the damaged strand. XRCC1 can also recruit end
      processing enzymes, such as PNK (polynucleotide kinase 3'-phosphatase), Aprataxin
      and APLF (aprataxin/PNK-like factor), which ensure the availability of a free 3'
      hydroxyl on one side of the gap, and a 5'-phosphate group on the other, for the
      polymerase and ligase reactions respectively. PNK binds to a phosphorylated
      segment of XRCC1 (between its two C-terminal BRCT domains) via its Forkhead
      associated (FHA) domain. We show here, contrary to previous studies, that the FHA
      domain of PNK binds specifically, and with high affinity to a multiply
      phosphorylated motif in XRCC1 containing a pSer-pThr dipeptide, and forms a 2:1
      PNK:XRCC1 complex. The high-resolution crystal structure of a PNK-FHA-XRCC1
      phosphopeptide complex reveals the basis for this unusual bis-phosphopeptide
      recognition, which is probably a common feature of the known XRCC1-associating
      end-processing enzymes.

PMID- 19155275
TI  - Real-time single-molecule observation of rolling-circle DNA replication.
AB  - We present a simple technique for visualizing replication of individual DNA
      molecules in real time. By attaching a rolling-circle substrate to a TIRF
      microscope-mounted flow chamber, we are able to monitor the progression of single
      DNA synthesis events and accurately measure rates and processivities of single T7
      and Escherichia coli replisomes as they replicate DNA. This method allows for
      rapid and precise characterization of the kinetics of DNA synthesis and the
      effects of replication inhibitors.

PMID- 19155276
TI  - Histone H3 Lys79 methylation is required for efficient nucleotide excision repair
      in a silenced locus of Saccharomyces cerevisiae.
AB  - Methylation of specific histone lysine residues regulates gene expression and
      heterochromatin function, but little is known about its role in DNA repair. To
      examine how changes in conserved methylated residues of histone H3 affect
      nucleotide excision repair (NER), viable H3K4R and H3K79R mutants were generated
      in Saccharomyces cerevisiae. These mutants show decreased UV survival and
      impaired NER at the transcriptionally silent HML locus, while maintaining normal
      NER in the constitutively expressed RPB2 gene and transcriptionally repressed,
      nucleosome loaded GAL10 gene. Moreover, the HML chromatin in these mutants has
      reduced accessibility to Micrococcal nuclease (MNase). Importantly, chromatin
      immunoprecipitation analysis demonstrates there is enhanced recruitment of the
      Sir complex at the HML locus of these mutants, and deletion of the SIR2 or SIR3
      genes restores the MNase accessibility and DNA repair efficiency at this locus.
      Furthermore, following UV irradiation expression of NER genes in these mutants
      remains at wild type levels, with the exception of RAD16 which decreases by more
      than 2-fold. These results indicate that impaired NER occurs in the silenced
      chromatin of H3K79R and H3K4,79R mutants as a result of increased binding of Sir
      complexes, which may reduce DNA lesion accessibility to repair enzymes.

PMID- 19155277
TI  - DNA models of trinucleotide frameshift deletions: the formation of loops and
      bulges at the primer-template junction.
AB  - Although mechanisms of single-nucleotide residue deletion have been investigated,
      processes involved in the loss of longer nucleotide sequences during DNA
      replication are poorly understood. Previous reports have shown that in vitro
      replication of a 3'-TGC TGC template sequence can result in the deletion of one
      3'-TGC. We have used low-energy circular dichroism (CD) and fluorescence
      spectroscopy to investigate the conformations and stabilities of DNA models of
      the replication intermediates that may be implicated in this frameshift.
      Pyrrolocytosine or 2-aminopurine residues, site-specifically substituted for
      cytosine or adenine in the vicinity of extruded base sequences, were used as
      spectroscopic probes to examine local DNA conformations. An equilibrium mixture
      of four hybridization conformations was observed when template bases looped-out
      as a bulge, i.e. a structure flanked on both sides by duplex DNA. In contrast, a
      single-loop structure with an unusual unstacked DNA conformation at its
      downstream edge was observed when the extruded bases were positioned at the
      primer-template junction, showing that misalignments can be modified by
      neighboring DNA secondary structure. These results must be taken into account in
      considering the genetic and biochemical mechanisms of frameshift mutagenesis in
      polymerase-driven DNA replication.

PMID- 19155278
TI  - Analysis of the eukaryotic topoisomerase II DNA gate: a single-molecule FRET and
      structural perspective.
AB  - Type II DNA topoisomerases (topos) are essential and ubiquitous enzymes that
      perform important intracellular roles in chromosome condensation and segregation,
      and in regulating DNA supercoiling. Eukaryotic topo II, a type II topoisomerase,
      is a homodimeric enzyme that solves topological entanglement problems by using
      the energy from ATP hydrolysis to pass one segment of DNA through another by way
      of a reversible, enzyme-bridged double-stranded break. This DNA break is linked
      to the protein by a phosphodiester bond between the active site tyrosine of each
      subunit and backbone phosphate of DNA. The opening and closing of the DNA gate, a
      critical step for strand passage during the catalytic cycle, is coupled to this
      enzymatic cleavage/religation of the backbone. This reversible DNA cleavage
      reaction is the target of a number of anticancer drugs, which can elicit DNA
      damage by affecting the cleavage/religation equilibrium. Because of its clinical
      importance, many studies have sought to determine the manner in which topo II
      interacts with DNA. Here we highlight recent single-molecule fluorescence
      resonance energy transfer and crystallographic studies that have provided new
      insight into the dynamics and structure of the topo II DNA gate.

PMID- 19155279
TI  - Update on immunotherapy for systemic lupus erythematosus--what's hot and what's
      not!
AB  - There have been significant advances in the treatment of SLE, which have produced
      major impacts on morbidity and in some cases mortality. The major drugs of the
      last three decades in treatment of SLE have been corticosteroids, AZA, MTX and
      cyclophosphamide. However, these drugs have considerable toxicities, and with the
      increasing knowledge of the immune system, and further understanding of SLE
      immunopathogenesis, many groups are seeking to identify and trial novel
      immunotherapeutic strategies. These have included therapies aimed at influencing
      particular immune cells (e.g. B cells) and molecules (e.g. costimulatory
      molecules, cytokines) which are thought to be important in disease pathogenesis.
      The advantage of such therapies is that efficacy may be achieved with lower
      toxicity, and without wide-ranging suppression of the immune system. Success has
      not always been achieved by specific design of immunotherapies for SLE, and the
      best recent example has been the use of B-cell depletion therapy, a concept
      derived from its successful use in RA. In this article, we discuss those
      immunotherapeutic strategies that have arrived as far as clinical trials in human
      subjects. In addition to these relatively specific immunotherapies, we also
      highlight the use of mycophenolate mofetil, an anti-proliferative
      immunosuppressant which has had good success over the last 10 yrs, with similar
      early efficacy to cyclophosphamide when used as induction therapy for lupus
      nephritis. Data are presented on more generalized immune strategies, such as the
      use of stem cell transplantation and intravenous immunoglobulin.

PMID- 19155280
TI  - Socioeconomic position, psychosocial work environment and cerebrovascular disease
      among women: the Finnish public sector study.
AB  - BACKGROUND: The excess risk of fatal and non-fatal cerebrovascular disease in
      people from low socioeconomic positions is only partially explained by
      conventional cerebrovascular risk factors. This has led to the suggestion that
      poor psychosocial work environments provide important additional explanatory
      power. However, little evidence is available for women. METHODS: We examined
      whether job demands or job control contributed to the socioeconomic gradient in
      cerebrovascular disease among 48 361 women aged 18-65 years. Job demands, job
      control and behavioural risk factors were self-reported in 2000-2002;
      socioeconomic position (as indexed by occupational class) and all of the health
      measures were obtained from registers. The outcome was recorded hospitalization
      or death from cerebrovascular disease. RESULTS: During a mean follow-up of 3.4
      years, 124 women had a new cerebrovascular disease event. The risk was 2.3 (95%
      CI 1.3-3.9) times higher among women in low vs high socioeconomic positions.
      Adjustment for conventional risk factors, such as prevalent hypertension,
      coronary heart disease, diabetes, smoking, heavy alcohol consumption, physical
      inactivity and obesity, attenuated this excess risk by 23%. In contrast,
      adjustment for job demands and job control actually amplified the gradient by 36%
      suggesting a suppression effect. CONCLUSIONS: In this contemporary cohort of
      employed women, job demands-alone and in combination with job control-suppressed
      rather than explained socioeconomic differences in cerebrovascular disease.

PMID- 19155281
TI  - Commentary: Closing the health gap for Indigenous Australians--will better
      counting mean better services and investment in the social production of health?

PMID- 19155282
TI  - Preoperative and postoperative chemotherapy with ifosfamide and adriamycin for
      adult high-grade soft-tissue sarcomas in the extremities: Japan Clinical Oncology
      Group Study JCOG0304.
AB  - This phase II clinical trial aims to evaluate the efficacies and toxicities of
      pre- and postoperative chemotherapy with adriamycin plus ifosfamide on the
      patients with soft-tissue high-grade sarcomas. Patients who have operable, non
      round cell soft-tissue sarcomas [French Federation of Cancer Center (FNCLCC)
      Grades 2 and 3] arising in the extremities [T2bN0M0, i.e. American Joint
      Committee on Cancer (AJCC) stage III] are treated by three courses of
      preoperative chemotherapy consisting of adriamycin and ifosfamide followed by
      complete resection and additional two courses of the same chemotherapy regimen.
      The Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical
      Oncology Group (JCOG) including 26 specialized institutes will accrue 75
      patients. The primary endpoint of the study is the 2-year progression-free
      survival rate, and secondary endpoints are response rate of the preoperative
      chemotherapy, 3-year progression-free survival rate, progression-free survival,
      overall survival and adverse events. The JCOG Clinical Trial Review Committee
      approved the protocol on 11 March 2004, and the study was started on 29 April
      2004. Protocol amendment was approved on 18 May 2007.

PMID- 19155284
TI  - A case of ductal carcinoma in situ of the breast.

PMID- 19155283
TI  - Genetic heterogeneity of EGFR mutation in pleomorphic carcinoma of the lung:
      response to gefitinib and clinical outcome.
AB  - Somatic epidermal growth factor receptor (EGFR) mutations in exons 19 and 21 have
      been found in non-small cell lung cancer (NSCLC) and are associated with the
      therapeutic response to gefitinib in patients with advanced NSCLC. We report a
      case of pleomorphic carcinoma of the lung with different EGFR mutations. Prior to
      gefitinib treatment, an exon 19 deletion of EGFR mutation was positive in the
      specimens obtained from pleural effusion and left cervical lymph node,
      histologically proven to be adenocarcinoma. However, the response to gefitinib
      was poor and the patient died of progressive disease 4 months after the
      initiation of gefitinib therapy. Postmortem examination revealed the major
      histological component to be of the sarcomatoid or pleomorphic type with scant
      mixed adenocarcinoma, resulting in a histological diagnosis of pleomorphic
      carcinoma of the lung. Although the adenocarcinomatous tissue was still positive
      for exon 19 deletion of EGFR mutation alone, sarcomatous components had both the
      exons 19 deletion and 20 T790M mutation concomitantly, thought to be a gefitinib
      resistance mutation. Pulmonary pleomorphic carcinoma is a rare NSCLC composed of
      biphasic and heterogeneous malignant cell populations. The present case suggested
      that expression of different EGFR mutations is related to the biphasic
      histological appearance in pulmonary pleomorphic carcinoma.

PMID- 19155285
TI  - Comparison of time trends in lung cancer incidence (1973-2002) in Asia, from
      cancer incidence in five continents Vols IV-IX.

PMID- 19155286
TI  - Endogenous galectins and the control of the host inflammatory response.
AB  - A new era of research is being devoted to deciphering endogenous mediators and
      mechanisms that are in place to resolve the inflammatory response. Accruing
      evidence indicates that galectins fall into this category of immunoregulatory
      mediators signifying their use as prospective novel anti-inflammatory agents. The
      focus of this review is to depict the immunoregulatory bioactivities of three
      members of the galectin superfamily, Galectin (Gal)-1, Gal-3 and Gal-9. Emphasis
      is given to the studies investigating the properties of these endogenous lectins.
      Gal-1, Gal-3 and Gal-9 are emerging as pertinent players in the modulation of
      acute and chronic inflammatory diseases, autoimmunity and cancer, and thus being
      increasingly recognised as molecular targets for innovative drug discovery.

PMID- 19155287
TI  - The causes of misdiagnosis and adverse outcomes in PGD.
AB  - The European Society of Human Reproduction and Embryology PGD Consortium has
      collected data on PGD cycles and deliveries since 1997. From 15,158 cycles, 24
      misdiagnoses and adverse outcomes have been reported; 12/2538 cycles after
      polymerase chain reaction and 12/12,620 cycles after fluorescence in situ
      hybridization. The causes of misdiagnosis include confusion of embryo and cell
      number, transfer of the wrong embryo, maternal or paternal contamination, allele
      dropout, use of incorrect and inappropriate probes or primers, probe or primer
      failure and chromosomal mosaicism. Unprotected sex has been mentioned as a cause
      of adverse outcome not related to technical and human errors. The majority of
      these causes can be prevented by using robust diagnostic methods within
      laboratories working to appropriate quality standards. However, diagnosis from a
      single cell remains a technically challenging procedure, and the risk of
      misdiagnosis cannot be eliminated.

PMID- 19155288
TI  - Using quality indicators to improve hospital care: a review of the literature.
AB  - PURPOSE: To review the literature concerning strategies for implementing quality
      indicators in hospital care, and their effectiveness in improving the quality of
      care. DATA SOURCES: A systematic literature study was carried out using MEDLINE
      and the Cochrane Library (January 1994 to January 2008). STUDY SELECTION:
      Hospital-based trials studying the effects of using quality indicators as a tool
      to improve quality of care. DATA EXTRACTION: Two reviewers independently assessed
      studies for inclusion, and extracted information from the studies included
      regarding the health care setting, type of implementation strategy and their
      effectiveness as a tool to improve quality of hospital care. RESULTS: A total of
      21 studies were included. The most frequently used implementation strategies were
      audit and feedback. The majority of these studies focused on care processes
      rather than patient outcomes. Six studies evaluated the effects of the
      implementation of quality indicators on patient outcomes. In four studies,
      quality indicator implementation was found to be ineffective, in one partially
      effective and in one it was found to be effective. Twenty studies focused on care
      processes, and most reported significant improvement with respect to part of the
      measured process indicators. The implementation of quality indicators in
      hospitals is most effective if feedback reports are given in combination with an
      educational implementation strategy and/or the development of a quality
      improvement plan. CONCLUSION: Effective strategies to implement quality
      indicators in daily practice in order to improve hospital care do exist, but
      there is considerable variation in the methods used and the level of change
      achieved. Feedback reports combined with another implementation strategy seem to
      be most effective.

PMID- 19155289
TI  - Spoken language scores of children using cochlear implants compared to hearing
      age-mates at school entry.
AB  - This study investigated three questions: Is it realistic to expect age
      appropriate spoken language skills in children with cochlear implants (CIs) who
      received auditory-oral intervention during the preschool years? What
      characteristics predict successful spoken language development in this
      population? Are children with CIs more proficient in some areas of language than
      others? We analyzed language skills of 153 children with CIs as measured by
      standardized tests. These children (mean age = 5 years and 10 months) attended
      programs in the United States (N = 39) that used an auditory-oral educational
      approach. Age-appropriate scores were observed in 50% of the children on measures
      of receptive vocabulary, 58% on expressive vocabulary, 46% on verbal
      intelligence, 47% on receptive language, and 39% on expressive language.
      Regression analysis indicated that, after controlling for the effects of
      nonverbal intelligence and parent education level, children who received their
      implants at young ages had higher scores on all language tests than children who
      were older at implantation. On average, children with CIs performed better on
      certain language measures than others, indicating that some areas of language may
      be more difficult for these children to master than others. Implications for
      educators of deaf children with CIs are discussed.

PMID- 19155290
TI  - The scavenger receptor CD36 plays a role in cytokine-induced macrophage fusion.
AB  - Multinucleated giant cells, characteristic of granulomatous infections, originate
      from the fusion of macrophages. Using an antibody screening strategy we found
      that the scavenger receptor CD36 participates in macrophage fusion induced by the
      cytokines IL-4 and GM-CSF. Our results demonstrate that exposure of
      phosphatidylserine on the cell surface and lipid recognition by CD36 are required
      for cytokine-induced fusion of macrophages. We also show that CD36 acts in a
      heterotypic manner during giant-cell formation and that the formation of
      osteoclasts is independent of CD36. The discovery of molecules involved in the
      formation of multinucleated giant cells will enable us to determine their
      functional significance. Furthermore, our results suggest that lipid capture by
      cell surface receptors may be a general feature of cell fusion.

PMID- 19155292
TI  - Emerging paradigms in cancer genetics: some important findings from high-density
      single nucleotide polymorphism array studies.
AB  - High-density single nucleotide polymorphism (SNP) mapping arrays have identified
      chromosomal features whose importance to cancer predisposition and progression is
      not yet clearly defined. Of interest is that the genomes of normal somatic cells
      (reflecting the combined parental germ-line contributions) often contain long
      homozygous stretches. These chromosomal segments may be explained by the common
      ancestry of the individual's parents and thus may also be called autozygous.
      Several studies link consanguinity to higher rates of cancer, suggesting that
      autozygosity (a genomic consequence of consanguinity) may be a factor in cancer
      predisposition. SNP array analysis has also identified chromosomal regions of
      somatic uniparental disomy (UPD) in cancer genomes. These are chromosomal
      segments characterized by loss of heterozygosity (LOH) and a normal copy number
      (two) but which are not autozygous in the germ-line or normal somatic cell
      genome. In this review, we will also discuss a model [cancer gene activity model
      (CGAM)] that may explain how autozygosity influences cancer predisposition. CGAM
      can also explain how the occurrence of certain chromosomal aberrations (copy
      number gain, LOH, and somatic UPDs) during carcinogenesis may be dependent on the
      germ-line genotypes of important cancer-related genes (oncogenes and tumor
      suppressors) found in those chromosomal regions.

PMID- 19155291
TI  - Limits to thymidylate synthase and TP53 genes as predictive determinants for
      fluoropyrimidine sensitivity and further evidence for RNA-based toxicity as a
      major influence.
AB  - The major determinants of 5-flurouracil (5-FU) response would seem, based on
      accumulated literature, to be thymidylate synthase (TYMS, TS) expression levels,
      TS gene modifications, and TP53 status. We tested 5-FU sensitivity in yeast and
      human cancer cell models in which TS or TP53 alleles and expression were varied.
      Polymorphic TS tandem repeat status, TS expression levels reported, TS intragenic
      mutations, and TP53 status in outbred and experimental cancer cell lines did not
      predict 5-FU sensitivity or resistance. Novel observations included a dose
      resistant persistence of unbound TS protein in many cancers and, upon 5-FU
      treatment of the colon cancer cell line, HCT116, evidence of allelic switching
      favoring transcripts of the mutant TS allele. The reported alleles having an
      intragenic mutation could not be causally associated with major degrees of 5-FU
      sensitivity. In yeast, TS protein was altered upon treatment with FdUMP, but 5-FU
      toxicity seemed to be largely RNA-based, being rescued by uridine rather than by
      thymidine. Cancer cell lines were also rescued from 5-FU toxicity with uridine
      rather than thymidine. Additionally, a TS (CDC21) knockout yeast strain,
      obviating any potential role for TS protein as a target, was hypersensitive to 5
      FU. When denatured proteins from cancer cells treated with radiolabeled 5-FU were
      labeled, species with alternative molecular weights other than TS were
      visualized, providing further evidence for alternative 5-FU protein targets.
      These data emphasize that TS and TP53 status do not consistently explain the
      variance in responses of fluoropyrimidine-treated cancer cells, in part due to
      RNA-based toxicity.

PMID- 19155293
TI  - Human postmeiotic segregation 2 exhibits biased repair at tetranucleotide
      microsatellite sequences.
AB  - The mismatch repair (MMR) system plays a major role in removing DNA
      polymerization errors, and loss of this pathway results in hereditary cancers
      characterized by microsatellite instability. We investigated microsatellite
      stability during DNA replication within human postmeiotic segregation 2 (hPMS2)
      deficient and proficient human lymphoblastoid cell lines. Using a shuttle vector
      assay, we measured mutation rates at reporter cassettes containing defined
      mononucleotide, dinucleotide, and tetranucleotide microsatellite sequences. A
      mutator phenotype was observed in the hPMS2-deficient cell line. The mutation
      rate of vectors containing [G/C](10) or [GT/CA](10) alleles was elevated 20-fold
      to 40-fold in hPMS2-deficient cells, relative to an hPMS2-expressing cell line.
      We observed a 6-fold and 12-fold relative increase in mutation rate of
      [TTTC/AAAG](9) and [TTCC/AAGG](9) sequences, respectively, in hPMS2-deficient
      cells. Mutational specificity analyses suggested that repair by hPMS2 is biased.
      In the absence of hPMS2, a greater number of microsatellite expansion versus
      deletion mutations was observed, and expansion rates of the tetranucleotide
      alleles were similar. In the presence of hPMS2, we observed a 29-fold decrease in
      the [TTCC/AAGG](9) expansion rate but only a 6-fold decrease for the
      [TTTC/AAAG](9) allele. Our data indicate that hPMS2 is more protective of
      tetranucleotide expansions than deletions and that hPMS2 displays a sequence
      bias, wherein [TTCC/AAGG] sequences are stabilized to a greater extent than
      [TTTC/AAAG]. Our results allow for greater accuracy during identification of MMR
      defects by providing a mutational signature characteristic of hPMS2 defect. This
      study also provides clues to possible mechanisms of repair by hPMS2 in the
      context of the MMR system.

PMID- 19155294
TI  - Consistent deregulation of gene expression between human and murine MLL
      rearrangement leukemias.
AB  - Important biological and pathologic properties are often conserved across
      species. Although several mouse leukemia models have been well established, the
      genes deregulated in both human and murine leukemia cells have not been studied
      systematically. We performed a serial analysis of gene expression in both human
      and murine MLL-ELL or MLL-ENL leukemia cells and identified 88 genes that seemed
      to be significantly deregulated in both types of leukemia cells, including 57
      genes not reported previously as being deregulated in MLL-associated leukemias.
      These changes were validated by quantitative PCR. The most up-regulated genes
      include several HOX genes (e.g., HOX A5, HOXA9, and HOXA10) and MEIS1, which are
      the typical hallmark of MLL rearrangement leukemia. The most down-regulated genes
      include LTF, LCN2, MMP9, S100A8, S100A9, PADI4, TGFBI, and CYBB. Notably, the up
      regulated genes are enriched in gene ontology terms, such as gene expression and
      transcription, whereas the down-regulated genes are enriched in signal
      transduction and apoptosis. We showed that the CpG islands of the down-regulated
      genes are hypermethylated. We also showed that seven individual microRNAs (miRNA)
      from the mir-17-92 cluster, which are overexpressed in human MLL rearrangement
      leukemias, are also consistently overexpressed in mouse MLL rearrangement
      leukemia cells. Nineteen possible targets of these miRNAs were identified, and
      two of them (i.e., APP and RASSF2) were confirmed further by luciferase reporter
      and mutagenesis assays. The identification and validation of consistent changes
      of gene expression in human and murine MLL rearrangement leukemias provide
      important insights into the genetic base for MLL-associated leukemogenesis.

PMID- 19155295
TI  - The transcriptional corepressor CtBP: a foe of multiple tumor suppressors.
AB  - CtBP1 and CtBP2 are closely related and evolutionarily conserved transcriptional
      corepressors. There is strong evidence linking CtBPs to tumorigenesis and tumor
      progression. CtBPs promote epithelial-mesenchymal transition and function as
      apoptosis antagonists. Also, CtBPs mediate repression of several tumor suppressor
      genes. Certain tumor suppressors also target CtBPs to restrain their tumor
      promoting activity. Down-regulation of CtBPs mediated by some tumor suppressors
      results in p53-independent apoptosis and reduced tumor cell migration and
      invasion. The role of CtBPs in modulating the activities of different tumor
      suppressors is reviewed here. The results discussed here suggest that CtBPs may
      constitute a novel p53-independent anticancer target.

PMID- 19155296
TI  - Transient receptor potential type vanilloid 1 suppresses skin carcinogenesis.
AB  - Blockade of the transient receptor potential channel vanilloid subfamily 1
      (TRPV1) is suggested as a therapeutic approach to pain relief. However, TRPV1 is
      a widely expressed protein whose function might be critical in various
      nonneuronal physiologic conditions. The epidermal growth factor receptor (EGFR)
      is a receptor tyrosine kinase that is overexpressed in many human epithelial
      cancers and is a potential target for anticancer drugs. Here, we show that TRPV1
      interacts with EGFR, leading to EGFR degradation. Notably, the absence of TRPV1
      in mice results in a striking increase in skin carcinogenesis. The TRPV1 is the
      first membrane receptor shown to have a tumor-suppressing effect associated with
      the down-regulation of another membrane receptor. The data suggest that, although
      a great deal of interest has focused on TRPV1 as a target for pain relief, the
      chronic blockade of this pain receptor might increase the risk for cancer
      development.

PMID- 19155297
TI  - Positron emission tomography (PET) imaging with [11C]-labeled erlotinib: a micro
      PET study on mice with lung tumor xenografts.
AB  - Erlotinib (Tarceva) targets the epidermal growth factor receptor (EGFR), which is
      commonly overexpressed in human cancers, including lung cancer. We show that
      erlotinib can be labeled with [(11)C] by reacting the normethyl precursor with
      [(11)C]-methyl iodide. By using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide proliferation assay, two lung cancer cell lines (A549
      and NCI358) were shown to be less sensitive to erlotinib compared with the lung
      cancer cell line HCC827. This correlated with higher expression and activity of
      the EGFR in HCC827 cells as compared with the less sensitive cell lines. Micro
      positron emission tomography (PET) and biodistribution of erlotinib was performed
      with [(11)C]-erlotinib in nude mice bearing xenografts of A549, NCI358, and
      HCC827 cells. Dynamic micro-PET showed that HCC827 tumors had the highest [(11)C]
      erlotinib uptake and retained the activity significantly longer as compared with
      A549 and NCI358 tumors. Biodistribution of [(11)C]-erlotinib in the xenograft
      models of lung cancer showed the highest accumulation in the liver. In mice
      carrying the sensitive cancer cells, the accumulation of [(11)C]-erlotinib was
      higher in tumors than in the other organs. In contrast, the drug accumulated to a
      comparable extent in tumors from the less sensitive cancer cells and the other
      organs. Uptake of [(11)C]-erlotinib in the tumors was 1.6%, 0.7%, and 3.7%
      (percentage of injected dose/g), in A549, NCI358, and HCC827 cells, respectively.
      We show for the first time that [(11)C]-erlotinib identifies erlotinib-sensitive
      tumors. These results pave the road for studies examining the benefit of [(11)C]
      erlotinib PET in patients with lung tumors or other tumors overexpressing EGFR.

PMID- 19155298
TI  - In-depth proteomics to define the cell surface and secretome of ovarian cancer
      cells and processes of protein shedding.
AB  - Current proteomics technologies allow substantial depth of analysis of cellular
      and subcellular proteomes as shown in the proteomic profiling of ovarian cancer
      cells. This in-depth analysis has elucidated the repertoire of proteins expressed
      on the cell surface and proteins released into the extracellular milieu,
      uncovering extensive shedding of extracellular domains of cell adhesion proteins
      and a highly dynamic protein secretion process. The protein sets identified
      provide a rich resource of potential circulating markers and targets for imaging
      and therapeutics for ovarian cancer.

PMID- 19155299
TI  - Loss of Rad51c leads to embryonic lethality and modulation of Trp53-dependent
      tumorigenesis in mice.
AB  - RecA/Rad51 protein family members (Rad51, Rad51b, Rad51c, Rad51d, Xrcc2, and
      Xrcc3) are essential for DNA repair by homologous recombination, and their role
      in cancers has been anticipated. Here we provide the first direct evidence for a
      tumor suppressor function for a member of the Rad51 family. We show that Rad51c
      deficiency leads to early embryonic lethality, which can be delayed on a Trp53
      null background. To uncover the role of Rad51c in tumorigenesis, we have
      exploited the fact that Rad51c and Trp53 are both closely located on the mouse
      chromosome 11. We have generated double heterozygous (DH) mice carrying mutant
      alleles of both genes either on different (DH-trans) or on the same chromosome
      (DH-cis), the latter allowing for a deletion of wild-type alleles of both genes
      by loss of heterozygosity. DH-trans mice, in contrast to DH-cis, developed tumors
      with latency and spectrum similar to Trp53 heterozygous mice. Strikingly, Rad51c
      mutation in DH-cis mice promoted the development of tumors of specialized
      sebaceous glands and suppressed tumors characteristic of Trp53 mutation. In
      addition, DH-cis females developed tumors significantly earlier than any other
      group.

PMID- 19155300
TI  - Large-scale profiling of archival lymph nodes reveals pervasive remodeling of the
      follicular lymphoma methylome.
AB  - Emerging technologies allow broad profiling of the cancer genome for differential
      DNA methylation relative to benign cells. Herein, bisulfite-modified DNA from
      lymph nodes with either reactive hyperplasia or follicular lymphoma (FL) were
      analyzed using a commercial C/UpG genotyping assay. Two hundred fifty-nine
      differentially methylated targets (DMT) distributed among 183 unique genes were
      identified in FL. Comparison of matched formalin-fixed, paraffin-embedded and
      frozen surgical pathology replicates showed the complete preservation of the
      cancer methylome among differently archived tissue specimens. Analysis of the DMT
      profile is consistent with a pervasive epigenomic remodeling process in FL that
      affects predominantly nonlymphoid genes.

PMID- 19155302
TI  - MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and
      suppresses tumorigenicity.
AB  - Although aberrant microRNA (miRNA) expressions have been observed in different
      types of cancer, their pathophysiologic role and their relevance to tumorigenesis
      are still largely unknown. In this study, we first evaluated the expression of
      308 miRNAs in human hepatocellular carcinoma (HCC) and normal hepatic tissues and
      identified 29 differentially expressed miRNAs in HCC tissues. miR-101, a
      significantly down-regulated miRNA, was further studied in greater detail because
      the signal pathway(s) regulated by miR-101 and the role of miR-101 in
      tumorigenesis have not yet been elucidated. Interestingly, decreased expression
      of miR-101 was found in all six hepatoma cell lines examined and in as high as
      94.1% of HCC tissues, compared with their nontumor counterparts. Furthermore,
      ectopic expression of miR-101 dramatically suppressed the ability of hepatoma
      cells to form colonies in vitro and to develop tumors in nude mice. We also found
      that miR-101 could sensitize hepatoma cell lines to both serum starvation- and
      chemotherapeutic drug-induced apoptosis. Further investigation revealed that miR
      101 significantly repressed the expression of luciferase carrying the 3'
      untranslated region of Mcl-1 and reduced the endogenous protein level of Mcl-1,
      whereas the miR-101 inhibitor obviously up-regulated Mcl-1 expression and
      inhibited cell apoptosis. Moreover, silencing of Mcl-1 phenocopied the effect of
      miR-101 and forced expression of Mcl-1 could reverse the proapoptotic effect of
      miR-101. These results indicate that miR-101 may exert its proapoptotic function
      via targeting Mcl-1. Taken together, our data suggest an important role of miR
      101 in the molecular etiology of cancer and implicate the potential application
      of miR-101 in cancer therapy.

PMID- 19155301
TI  - Senescent stromal-derived osteopontin promotes preneoplastic cell growth.
AB  - Alterations in the tissue microenvironment collaborate with cell autonomous
      genetic changes to contribute to neoplastic progression. The importance of the
      microenvironment in neoplastic progression is underscored by studies showing that
      fibroblasts isolated from a tumor stimulate the growth of preneoplastic and
      neoplastic cells in xenograft models. Similarly, senescent fibroblasts promote
      preneoplastic cell growth in vitro and in vivo. Because senescent cells
      accumulate with age, their presence is hypothesized to facilitate preneoplastic
      cell growth and tumor formation in older individuals. To identify senescent
      stromal factors directly responsible for stimulating preneoplastic cell growth,
      we carried out whole-genome transcriptional profiling and compared senescent
      fibroblasts with their younger counterparts. We identified osteopontin (OPN) as
      one of the most highly elevated transcripts in senescent fibroblasts.
      Importantly, reduction of OPN protein levels by RNA interference did not affect
      senescence induction in fibroblasts; however, it dramatically reduced the growth
      promoting activities of senescent fibroblasts in vitro and in vivo, showing that
      OPN is necessary for paracrine stimulation of preneoplastic cell growth. In
      addition, we found that recombinant OPN was sufficient to stimulate preneoplastic
      cell growth. Finally, we show that OPN is expressed in senescent stroma within
      preneoplastic lesions that arise following 7,12-dimethylbenz(a)anthracene/12-O
      tetradecanoylphorbol-13-acetate treatment of mice, suggesting that stromal
      derived OPN-mediated signaling events affect neoplastic progression.

PMID- 19155303
TI  - Tamoxifen induces expression of immune response-related genes in cultured normal
      human mammary epithelial cells.
AB  - Use of tamoxifen is associated with a 50% reduction in breast cancer incidence
      and an increase in endometrial cancer incidence. Here, we documented tamoxifen
      induced gene expression changes in cultured normal human mammary epithelial cells
      (strains 5, 16, and 40), established from tissue taken at reduction mammoplasty
      from three individuals. Cells exposed to 0, 10, or 50 micromol/L of tamoxifen for
      48 hours were evaluated for (E)-alpha-(deoxyguanosine-N(2)-yl)-tamoxifen (dG-N(2)
      TAM) adduct formation using TAM-DNA (DNA modified with dG-N(2)-TAM)
      chemiluminescence immunoassay, gene expression changes using National Cancer
      Institute DNA-oligonucleotide microarray, and real-time PCR. At 48 hours, cells
      exposed to 10 and 50 micromol/L of tamoxifen were 85.6% and 48.4% viable,
      respectively, and there were no measurable dG-N(2)-TAM adducts. For microarrays,
      cells were exposed to 10 micromol/L of tamoxifen and genes with expression
      changes of >3-fold were as follows: 13 genes up-regulated and 1 down-regulated
      for strain 16; 17 genes up-regulated for strain 5, and 11 genes up-regulated for
      strain 40. Interferon-inducible genes (IFITM1, IFIT1, MXI, and GIP3), and a
      potassium ion channel (KCNJ1) were up-regulated in all three strains. No
      significant expression changes were found for genes related to estrogen or
      xenobiotic metabolism. Real-time PCR revealed the up-regulation of IFNA1 and
      confirmed the tamoxifen-induced up-regulation of the five other genes identified
      by microarray, with the exception of GIP3 and MX1, which were not up-regulated in
      strain 40. Induction of IFN-related genes in the three normal human mammary
      epithelial cell strains suggests that, in addition to hormonal effects, tamoxifen
      exposure may enhance immune response in normal breast tissue.

PMID- 19155304
TI  - Longitudinal diffusion tensor magnetic resonance imaging study of radiation
      induced white matter damage in a rat model.
AB  - Radiation-induced white matter (WM) damage is a major side effect of whole brain
      irradiation among childhood cancer survivors. We evaluate longitudinally the
      diffusion characteristics of the late radiation-induced WM damage in a rat model
      after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48
      weeks postradiation. We hypothesize that diffusion tensor magnetic resonance
      imaging (DTI) indices including fractional anisotropy (FA), trace, axial
      diffusivity (lambda(//)), and radial diffusivity (lambda( perpendicular)) can
      accurately detect and monitor the histopathologic changes of radiation-induced WM
      damage, measured at the EC, and that these changes are dose and time dependent.
      Results showed a progressive reduction of FA, which was driven by reduction in
      lambda(//) from 4 to 40 weeks postradiation, and an increase in lambda(
      perpendicular) with return to baseline in lambda(//) at 48 weeks postradiation.
      Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks
      postradiation with reversal at 36 weeks, and demyelination, axonal degeneration,
      and necrosis at 48 weeks postradiation. Moreover, changes in lambda(//)
      correlated with reactive astrogliosis (P < 0.01) and lambda( perpendicular)
      correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced
      earlier and more severe histologic changes than lower radiation dose (25 Gy), and
      these differences were reflected by the magnitude of changes in lambda(//) and
      lambda( perpendicular). DTI indices reflected the histopathologic changes of WM
      damage and our results support the use of DTI as a biomarker to noninvasively
      monitor radiation-induced WM damage.

PMID- 19155305
TI  - Glucocorticoid-induced tumor necrosis factor receptor-related protein ligand
      subverts immunosurveillance of acute myeloid leukemia in humans.
AB  - The reciprocal interaction of tumor cells with the immune system is influenced by
      various members of the tumor necrosis factor (TNF)/TNF receptor (TNFR) family,
      and recently, glucocorticoid-induced TNFR-related protein (GITR) was shown to
      stimulate antitumor immunity in mice. However, GITR may mediate different effects
      in mice and men and impairs the reactivity of human natural killer (NK) cells.
      Here, we studied the role of GITR and its ligand (GITRL) in human acute myeloid
      leukemia (AML). Surface expression of GITRL was observed on AML cells in six of
      seven investigated cell lines, and 34 of 60 investigated AML patients whereas
      healthy CD34(+) cells did not express GITRL. Furthermore, soluble GITRL (sGITRL)
      was detectable in AML patient sera in 18 of 55 investigated cases. While the
      presence of GITRL was not restricted to a specific AML subtype, surface
      expression was significantly associated with monocytic differentiation. Signaling
      via GITRL into patient AML cells induced the release of TNF and interleukin-10
      (IL-10), and this was blocked by the inhibition of mitogen-activated protein
      kinases extracellular signal-regulated kinase 1/2. Furthermore, triggering GITR
      by surface-expressed and sGITRL impaired NK cell cytotoxicity and IFN-gamma
      production in cocultures with leukemia cells, and NK cell reactivity could be
      restored by blocking GITR and neutralization of sGITRL and IL-10. Thus, whereas a
      stimulatory role of the GITR-GITRL system in mouse antitumor immunity has been
      reported, our data show that in humans GITRL expression subverts NK cell
      immunosurveillance of AML. Our results provide useful information for therapeutic
      approaches in AML, which, like haploidentical stem cell transplantation, rely on
      a sufficient NK cell response.

PMID- 19155306
TI  - Inhibition of the peptidyl-prolyl-isomerase Pin1 enhances the responses of acute
      myeloid leukemia cells to retinoic acid via stabilization of RARalpha and PML
      RARalpha.
AB  - The peptidyl-prolyl-isomerase Pin1 interacts with phosphorylated proteins,
      altering their conformation. The retinoic acid receptor RARalpha and the acute
      promyelocytic-leukemia-specific counterpart PML-RARalpha directly interact with
      Pin1. Overexpression of Pin1 inhibits ligand-dependent activation of RARalpha and
      PML-RARalpha. Inhibition is relieved by Pin1-targeted short interfering RNAs and
      by pharmacologic inhibition of the catalytic activity of the protein. Mutants of
      Pin1 catalytically inactive or defective for client-protein-binding activity are
      incapable of inhibiting ligand-dependent RARalpha transcriptional activity.
      Functional inhibition of RARalpha and PML-RARalpha by Pin1 correlates with
      degradation of the nuclear receptors via the proteasome-dependent pathway. In the
      acute myelogenous leukemia cell lines HL-60 and NB4, Pin1 interacts with RARalpha
      in a constitutive fashion. Suppression of Pin1 by a specific short hairpin RNA in
      HL-60 or NB4 cells stabilizes RARalpha and PML-RARalpha, resulting in increased
      sensitivity to the cytodifferentiating and antiproliferative activities of all
      trans retinoic acid. Treatment of the two cell lines and freshly isolated acute
      myelogenous leukemia blasts (M1 to M4) with ATRA and a pharmacologic inhibitor of
      Pin1 causes similar effects. Our results add a further layer of complexity to the
      regulation of nuclear retinoic acid receptors and suggest that Pin1 represents an
      important target for strategies aimed at increasing the therapeutic index of
      retinoids.

PMID- 19155307
TI  - IFN regulatory factor 8 sensitizes soft tissue sarcoma cells to death receptor
      initiated apoptosis via repression of FLICE-like protein expression.
AB  - IFN regulatory factor 8 (IRF8) has been shown to suppress tumor development at
      least partly through regulating apoptosis of tumor cells; however, the molecular
      mechanisms underlying IRF8 regulation of apoptosis are still not fully
      understood. Here, we showed that disrupting IRF8 function resulted in inhibition
      of cytochrome c release, caspase-9 and caspase-3 activation, and poly(ADP-ribose)
      polymerase cleavage in soft tissue sarcoma (STS) cells. Inhibition of the
      mitochondrion-dependent apoptosis signaling cascade is apparently due to blockage
      of caspase-8 and Bid activation. Analysis of signaling events upstream of caspase
      8 revealed that disrupting IRF8 function dramatically increases FLIP mRNA
      stability, resulting in increased IRF8 protein level. Furthermore, primary
      myeloid cells isolated from IRF8-null mice also exhibited increased FLIP protein
      level, suggesting that IRF8 might be a general repressor of FLIP. Nuclear IRF8
      protein was absent in 92% (55 of 60) of human STS specimens, and 99% (59 of 60)
      of human STS specimens exhibited FLIP expression, suggesting that the nuclear
      IRF8 protein level is inversely correlated with FLIP level in vivo. Silencing
      FLIP expression significantly increased human sarcoma cells to both FasL-induced
      and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced
      apoptosis, and ectopic expression of IRF8 also significantly increased the
      sensitivity of these human sarcoma cells to FasL- and TRAIL-induced apoptosis.
      Taken together, our data suggest that IRF8 mediates FLIP expression level to
      regulate apoptosis and targeting IRF8 expression is a potentially effective
      therapeutic strategy to sensitize apoptosis-resistant human STS to apoptosis,
      thereby possibly overcoming chemoresistance of STS, currently a major obstacle in
      human STS therapy.

PMID- 19155308
TI  - A requirement for cyclin-dependent kinase 6 in thymocyte development and
      tumorigenesis.
AB  - Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is
      overexpressed in human lymphoid malignancies. To determine the role of CDK6 in
      development and tumorigenesis, we generated and analyzed knockout mice. Cdk6
      deficient mice show pronounced thymic atrophy due to reduced proliferative
      fractions and concomitant transitional blocks in the double-negative stages.
      Using the OP9-DL1 system to deliver temporally controlled Notch receptor
      dependent signaling, we show that CDK6 is required for Notch-dependent survival,
      proliferation, and differentiation. Furthermore, CDK6-deficient mice were
      resistant to lymphomagenesis induced by active Akt, a downstream target of Notch
      signaling. These results show a critical requirement for CDK6 in Notch/Akt
      dependent T-cell development and tumorigenesis and strongly support CDK6 as a
      specific therapeutic target in human lymphoid malignancies.

PMID- 19155309
TI  - Beta1 integrin adhesion enhances IL-6-mediated STAT3 signaling in myeloma cells:
      implications for microenvironment influence on tumor survival and proliferation.
AB  - The bone marrow microenvironmental components interleukin (IL)-6 and fibronectin
      (FN) individually influence the proliferation and survival of multiple myeloma
      (MM) cells; however, in vivo, these effectors most likely work together. We
      examined signaling events, cell cycle progression, and levels of drug response in
      MM cells either adhered to FN via beta1 integrins, stimulated with IL-6, or
      treated with the two combined. Although G(1)-S cell cycle arrest associated with
      FN adhesion was overcome when IL-6 was added, the cell adhesion-mediated drug
      resistance (CAM-DR) was maintained in the presence of IL-6. Concomitant exposure
      of MM cells to IL-6 and FN adhesion revealed a dramatic increase in signal
      transducers and activators of transcription 3 (STAT3) phosphorylation, nuclear
      translocation, and DNA binding, compared with either IL-6 or FN adhesion alone in
      four MM cell lines. Importantly, this increase in STAT3 activation correlated
      with a novel association between STAT3 and gp130 in cells adhered to FN before
      stimulation with IL-6, relative to nonadherent cells. Taken together, these
      results suggest a mechanism by which collaborative signaling by beta1 integrin
      and gp130 confers an increased survival advantage to MM cells.

PMID- 19155310
TI  - ADP-ribosylation factor 6 regulates glioma cell invasion through the IQ-domain
      GTPase-activating protein 1-Rac1-mediated pathway.
AB  - A common pathobiological feature of malignant gliomas is the insidious
      infiltration of single tumor cells into the brain parenchyma, rendering these
      deadly tumors virtually incurable with available therapies. In this study, we
      report that ADP-ribosylation factor 6 (ARF6), a Ras superfamily small GTPase, is
      abundantly expressed in invasive human glioma cells. Cellular depletion of ARF6
      by small interfering RNA decreased Rac1 activation, impaired HGF-stimulated and
      serum-stimulated glioma cell migration in vitro, and markedly decreased the
      invasive capacity of invasive glioma in the brain. Furthermore, ectopic
      expression of ARF6 in glioma cells promoted cell migration via the activation of
      Rac1. Upon stimulation of glioma cells with HGF, we show that IQ-domain GTPase
      activating protein 1 (IQGAP1) is recruited and overlaps with ARF6 at the leading
      edge of migrating cells. However, cellular depletion of ARF6 abrogated this
      recruitment of IQGAP1 and attenuated the formation of surface protrusions. ARF6
      forms complexes with Rac1 and IQGAP1 in glioma cells upon HGF stimulation, and
      knockdown of IQGAP1 significantly inhibits ARF6-induced Rac1 activation and cell
      migration. Taken together, these data suggest that ARF6-mediated Rac1 activation
      is essential for glioma cell invasion via a signaling pathway that requires
      IQGAP1.

PMID- 19155311
TI  - Membrane microvesicles as actors in the establishment of a favorable prostatic
      tumoral niche: a role for activated fibroblasts and CX3CL1-CX3CR1 axis.
AB  - Tumor microenvironment is enriched in plasma membrane microvesicles (MV) shed
      from all cell types that constitute the tumor mass, reflecting the antigenic
      profile of the cells they originate from. Fibroblasts and tumor cells mutually
      communicate within tumor microenvironment. Recent evidences suggest that tumor
      derived MVs (TMV) exert a broad array of biological functions in cell-to-cell
      communication. To elucidate their role in cancer-to-fibroblast cell
      communication, TMV obtained from two prostate carcinoma cell lines with high and
      weak metastatic potential (PC3 and LnCaP, respectively) have been characterized.
      TMV exhibit matrix metalloproteinases (MMP) and extracellular MMP inducer at
      their surface, suggesting a role in extracellular matrix degradation. Moreover,
      TMV not only induce the activation of fibroblasts assessed through extracellular
      signal-regulated kinase 1/2 phosphorylation and MMP-9 up-regulation, increase
      motility and resistance to apoptosis but also promote MV shedding from activated
      fibroblasts able in turn to increase migration and invasion of highly metastatic
      PC3 cells but not LnCaP cells. PC3 cell chemotaxis seems, at least partially,
      dependent on membrane-bound CX3CL1/fractalkine ligand for chemokine receptor
      CX3CR1. The present results highlight a mechanism of mutual communication
      attributable not only to soluble factors but also to determinants harbored by MV,
      possibly contributing to the constitution of a favorable niche for cancer
      development.

PMID- 19155312
TI  - Smad ubiquitination regulatory factor 2 promotes metastasis of breast cancer
      cells by enhancing migration and invasiveness.
AB  - Controlled protein degradation mediated by ubiquitin/proteasome system (UPS)
      plays a crucial role in modulating a broad range of cellular responses.
      Dysregulation of the UPS often accompanies tumorigenesis and progression. Here,
      we report that Smad ubiquitination regulatory factor 2 (Smurf2), a HECT-domain
      containing E3 ubiquitin ligase, is up-regulated in certain breast cancer tissues
      and cells. We show that reduction of Smurf2 expression with specific short
      interfering RNA in metastatic breast cancer cells induces cell rounding and
      reorganization of the actin cytoskeleton, which are associated with a less motile
      and invasive phenotype. Overexpression of Smurf2 promotes metastasis in a nude
      mouse model and increases migration and invasion of breast cancer cells.
      Moreover, expression of Smurf2CG, an E3 ligase-defective mutant of Smurf2,
      suppresses the above metastatic behaviors. These results establish an important
      role for Smurf2 in breast cancer progression and indicate that Smurf2 is a novel
      regulator of breast cancer cell migration and invasion.

PMID- 19155313
TI  - Antitumor effects of a combined 5-aza-2'deoxycytidine and valproic acid treatment
      on rhabdomyosarcoma and medulloblastoma in Ptch mutant mice.
AB  - Patched (Ptch) heterozygous mice develop medulloblastoma (MB) and
      rhabdomyosarcoma (RMS) resembling the corresponding human tumors. We have
      previously shown that epigenetic silencing of the intact Ptch allele contributes
      to tumor formation in this model. Here, we investigated whether targeting of
      epigenetic silencing mechanisms could be useful in the treatment of Ptch
      associated cancers. A reduction of endogenous DNA methyltransferase1 (Dnmt1)
      activity significantly reduced tumor incidence in heterozygous Ptch knockout
      mice. A combined treatment with the Dnmt inhibitor 5-aza-2'deoxycytidine (5-aza
      dC) and the histone deacetlyase (HDAC) inhibitor valproic acid (VPA) efficiently
      prevented MB and RMS formation, whereas monotherapies with either drug were less
      effective. Wild-type Ptch expression was efficiently reactivated in tumors by 5
      aza-dC/VPA combination therapy. This was associated with reduced methylation of
      the Ptch promoter and induction of histone hyperacetylation suggesting inhibition
      of HDACs in vivo. However, the treatment was not effective in clinically overt,
      advanced stage tumors. This is a first in vivo demonstration that targeting of
      Dnmt and HDAC activities is highly effective in preventing formation of Ptch
      associated tumors. The results suggest a novel clinical strategy for
      consolidation therapy of corresponding tumors in humans after completion of
      conventional treatment. Our data also suggest that epigenetic therapy may be less
      effective in treating advanced stages of tumors, at least in this tumor model.

PMID- 19155315
TI  - The bifid median nerve re-visited.
AB  - This report presents a venous malformation arising from the persistent median
      vessels associated with a bifid median nerve. The literature on bifid median
      nerve is reviewed and a classification of its associated abnormalities is
      offered.

PMID- 19155314
TI  - Multidrug resistance decreases with mutations of melanosomal regulatory genes.
AB  - Whereas resistance to chemotherapy has long impeded effective treatment of
      metastatic melanoma, the mechanistic basis of this resistance remains unknown.
      One possible mechanism of drug resistance is alteration of intracellular drug
      distribution either by drug efflux or sequestration into intracellular
      organelles. Melanomas, as well as primary melanocytes from which they arise, have
      intracellular organelles, called melanosomes, wherein the synthesis and storage
      of the pigment melanin takes place. In this study, comparisons of congenic cells
      with and without functional molecules regulating melanosome formation show that
      sensitivity to the chemotherapeutic agent cis-diaminedichloroplatinum II (cis
      platin) significantly increases with the mutation of genes regulating melanosome
      formation, concomitant disruption of melanosome morphology, and loss of mature
      melanosomes. Absence of the melanosomal structural protein gp100/Pmel17 causes
      increased cis-platin sensitivity. Independent mutations in three separate genes
      that regulate melanosome biogenesis (Dtnbp1, Pldn, Vps33a) also result in
      increased cis-platin sensitivity. In addition, a mutation of the gene encoding
      the integral melanosomal protein tyrosinase, resulting in aberrant melanosome
      formation, also causes increased cis-platin sensitivity. Furthermore, sensitivity
      to agents in other chemotherapeutic classes (e.g., vinblastine and etoposide)
      also increased with the mutation of Pldn. In contrast, a mutation in another
      melanosomal regulatory gene, Hps1, minimally affects melanosome biogenesis,
      preserves the formation of mature melanosomes, and has no effect on cis-platin or
      vinblastine response. Together, these data provide the first direct evidence that
      melanosomal regulatory genes influence drug sensitivity and that the presence of
      mature melanosomes likely contributes to melanoma resistance to therapy.

PMID- 19155316
TI  - The syndrome of gastric carcinoid and hyperparathyroidism: a family study and
      literature review.
AB  - OBJECTIVE: To present evidence supporting the hypothesis that the coexistence of
      gastric carcinoids (GCs) and hyperparathyroidism may represent a distinct
      clinical entity, not related to multiple endocrine neoplasia type 1 (MEN1).
      METHODS: We studied a cohort of five young siblings (age range 26-42 years), one
      of whom had been found to have GC and hyperparathyroidism. All siblings underwent
      serial gastroscopies for the assessment of gastric neuroendocrine cell
      proliferations over a mean follow-up period of 31.2 months. Imaging, biochemical
      and hormonal as well as molecular genetic investigations were performed in the
      direction of MEN1 syndrome. The literature was searched for cases with
      coexistence of GCs and hyperparathyroidism not associated with MEN1. RESULTS:
      Four of the siblings, all male, were found to have GCs in a background of
      Helicobacter pylori-associated chronic atrophic gastritis and pernicious anaemia,
      with no serological evidence of gastric autoimmunity. In two of them,
      asymptomatic hyperparathyroidism was also present. Screening for MEN1 gene
      mutations or large deletions was negative, and hormone and imaging investigations
      did not support a diagnosis of familial MEN1 syndrome. A literature search
      revealed sporadic reports of cases with GC and hyperparathyroidism not
      attributable to MEN1. CONCLUSIONS: The association of GCs and hyperparathyroidism
      appears to constitute a distinct syndrome that can be encountered in genetically
      predisposed individuals, and should not be regarded as 'atypical' or 'incomplete'
      expression of MEN1. Its prevalence and aetiology should be the subject of future
      studies. Screening for hyperparathyroidism seems to be justified in patients with
      GC of any type.

PMID- 19155317
TI  - Retinoic acid receptor and retinoid X receptor subtype expression for the
      differential diagnosis of thyroid neoplasms.
AB  - BACKGROUND: Although differential expression of retinoic acid receptor (RAR)
      subtypes between benign and malignant thyroid tissues has been described, their
      diagnostic value has not been reported. AIM: To investigate the diagnostic
      accuracy of RAR and retinoid X receptor (RXR) subtype protein expression for the
      differential diagnosis of thyroid neoplasms. METHODS: We used a tissue array
      containing 93 benign thyroid tissues (normal thyroid, multinodular goiter, and
      follicular adenoma (FA)) and 77 thyroid carcinomas (papillary thyroid carcinoma
      (PTC), follicular thyroid carcinoma, and follicular variant of PTC (FVPTC)).
      Immunostaining was done for RAR and RXR subtypes. Staining was analyzed
      semiquantitatively based on receiver operating curve analyses and using
      hierarchical cluster analysis. RESULTS: We found increased expression of
      cytoplasmic (c) RARA, cRARG, cRXRB and decreased expression of nuclear (n) RARB,
      nRARG, and nRXRA in thyroid carcinomas compared with benign tissues. We found
      three proteins differently expressed between FA and FTC and five proteins
      differentially expressed between FA and FVPTC, with high diagnostic accuracies.
      Using cluster analysis, the combination of negative staining of membranous RXRB
      and positive staining for cRXRB had a high positive predictive value (98%) for
      malignant thyroid disease, whereas the combination of positive nRXRA and negative
      cRXRB staining had a high predictive value (91%) for benign thyroid lesions.
      CONCLUSION: We conclude that differences in RAR and RXR subtype protein
      expression may be valuable for the differential diagnosis of thyroid neoplasms.
      The results of this study and especially the value of cluster analysis have to be
      confirmed in subsequent studies.

PMID- 19155318
TI  - Secretion of adiponectin multimeric complexes from adipose tissue explants is not
      modified by very low calorie diet.
AB  - OBJECTIVE: Adiponectin is a protein abundantly secreted by the adipose tissue
      (AT). Plasma adiponectin levels are decreased in obese, insulin-resistant, and
      type 2 diabetic patients. Various multimeric complexes, i.e. high-, middle-, and
      low-molecular weight isoforms (HMW, MMW and LMW), are present in plasma. Here, we
      investigated the effect of weight reducing diet on the distribution of
      adiponectin isoforms in plasma and on their secretion in AT explants from obese
      subjects. DESIGN: A total of 20 obese subjects (age 37.8+/-7.3 years, body mass
      index 33.9+/-5.0 kg/m(2)) underwent eight weeks of very low-calorie diet (VLCD).
      A needle biopsy of subcutaneous abdominal AT and blood samples were taken before
      and after dietary intervention. AT explants were incubated in culture medium for
      4 h. ELISA assay and western blot analyses were used to identify adiponectin
      complexes in culture media and in plasma. RESULTS: The distribution of
      adiponectin polymers in plasma was different from that secreted in human AT
      explants. Before VLCD, the relative amount of HMW isoform was 75.5+/-9.1% of
      total adiponectin in culture media and 52.2+/-11.2% in plasma. Despite the diet
      induced weight loss and improvement of insulin sensitivity, VLCD neither induced
      change in total adiponectin level nor in the ratio of HMW to total adiponectin in
      plasma and in culture media of AT explants. CONCLUSIONS: The profile of
      adiponectin polymeric isoforms secreted by AT explants into culture media differs
      from the plasma profile. A dietary intervention leading to weight loss and
      improvement of insulin sensitivity was not associated with modifications of AT
      secretion of total or HMW adiponectin.

PMID- 19155319
TI  - Small for gestational age status is associated with metabolic syndrome in
      overweight children.
AB  - OBJECTIVE: Small for gestational age (SGA) children are at risk of both later
      obesity and metabolic syndrome (MetS). However, it is unknown whether obesity or
      SGA status leads to MetS in these subjects. We hypothesized that overweight
      children with former SGA status had more present components of the MetS than
      overweight children with former appropriate for gestational age (AGA) status.
      METHODS: We analyzed 803 overweight children (4% SGA, mean age 11+/-0.1 years,
      body mass index (BMI) 27.3+/-0.2, SDS-BMI 2.32+/-0.02) concerning blood pressure,
      lipids, glucose, and insulin. Oral glucose tolerance tests (oGTT) were performed
      in all 35 former SGA children and 147 randomly chosen former non-SGA children.
      RESULTS: After adjustment for age, sex, pubertal stage, and BMI-SDS, former SGA
      status was significantly related to blood pressure, triglyceride, insulin, and 2
      h glucose levels in oGTT. The MetS prevalence was more than doubled in overweight
      former SGA subjects (40% MetS) compared with overweight former AGA subjects (17%
      MetS). The corresponding adjusted odds ratio was 4.08 (95% confidence interval
      1.48 to 11.22) for SGA compared with AGA children. CONCLUSIONS: Overweight former
      SGA children had an increased risk for the components of the MetS compared with
      overweight former AGA children. Therefore, SGA status seems to be a risk factor
      for the MetS independently of weight status. Particularly overweight children
      with former SGA status should be screened for the MetS.

PMID- 19155320
TI  - The SID-1 double-stranded RNA transporter is not selective for dsRNA length.
AB  - The double-stranded RNA (dsRNA) transport protein SID-1 enables systemic RNA
      interference (RNAi) in Caenorhabditis elegans, whereby silencing initiated by
      local exposure to dsRNA spreads throughout the animal and to its progeny.
      Previously, we showed that providing dsRNA in the growth medium of Drosophila S2
      cells that express C. elegans SID-1 efficiently triggers RNAi. In these
      experiments long dsRNA proved to be significantly more effective than short dsRNA
      in silencing the target gene. Here, we show that equivalent masses of long or
      short dsRNA accumulate in these cells, indicating that size-dependent silencing
      is not due to size-selective transport through SID-1. Furthermore, using pulse
      chase dsRNA uptake experiments, we show that short dsRNA accumulates more rapidly
      than long dsRNA. We found that import rates are dependent on dsRNA concentration,
      consistent with energy-independent, diffusion-limited transport through the SID-1
      channel. Comparison of silencing efficiencies between Drosophila S2 cells
      heterologously expressing SID-1 and primary-cultured C. elegans cells shows
      similar dsRNA concentration and size dependencies, suggesting that C. elegans
      regulatory proteins do not measurably enhance or restrict dsRNA transport through
      SID-1. Finally, we find that coexpressing mutant SID-1 with wild-type SID-1 in S2
      cells interferes with SID-1 function, indicating that SID-1 may function as a
      multimer.

PMID- 19155321
TI  - Uncoupling of lin-14 mRNA and protein repression by nutrient deprivation in
      Caenorhabditis elegans.
AB  - In animals, microRNAs (miRNAs), typically, pair to sites of partial
      complementarity in the 3'-untranslated regions (3'UTRs) of target genes.
      Regulation by miRNAs often results in down-regulation of target mRNA and protein
      expression by mechanisms that are yet to be fully elucidated. Additionally,
      changes in environmental conditions have been shown to influence miRNA function
      in some cell culture systems. Here, we report the effect of nutrient deprivation
      on regulation of an endogenous miRNA target in developing worms. In
      Caenorhabditis elegans, the lin-4 miRNA recognizes multiple sites in the lin-14
      3'UTR and directs mRNA degradation and translational repression, but it is
      unclear how these processes are coupled. In this study, we demonstrate that
      nutrient deprivation results in loss of lin-14 mRNA, but not protein, repression.
      In worms removed from feeding conditions, lin-14 mRNA reaccumulates despite the
      continued expression of lin-4 miRNA. The relative increase in lin-14 mRNA levels
      during nutrient deprivation is less pronounced in genetic mutants lacking lin-4
      miRNA or the lin-14 3'UTR target sites. In conclusion, regulation of lin-14 at
      the mRNA and protein levels can be uncoupled by changes in culture conditions,
      indicating that miRNA function can be modulated by environment in multicellular
      organisms. The awareness that endogenous miRNA pathways can be sensitive to
      environment is an important consideration for elucidating the mechanism used by
      miRNAs to regulate target mRNA and protein expression.

PMID- 19155322
TI  - EcI5, a group IIB intron with high retrohoming frequency: DNA target site
      recognition and use in gene targeting.
AB  - We find that group II intron EcI5, a subclass CL/IIB1 intron from an Escherichia
      coli virulence plasmid, is highly active in retrohoming in E. coli. Both full
      length EcI5 and an EcI5-DeltaORF intron with the intron-encoded protein expressed
      separately from the same donor plasmid retrohome into a recipient plasmid target
      site at substantially higher frequencies than do similarly configured Lactococcus
      lactis Ll.LtrB introns. A comprehensive view of DNA target site recognition by
      EcI5 was obtained from selection experiments with donor and recipient plasmid
      libraries in which different recognition elements were randomized. These
      experiments suggest that EcI5, like other mobile group II introns, recognizes DNA
      target sequences by using both the intron-encoded protein and base-pairing of the
      intron RNA, with the latter involving EBS1, EBS2, and EBS3 sequences
      characteristic of class IIB introns. The intron-encoded protein appears to
      recognize a small number of bases flanking those recognized by the intron RNA,
      but their identity is different than in previously characterized group II
      introns. A computer algorithm based on the empirically determined DNA recognition
      rules enabled retargeting of EcI5 to integrate specifically at 10 different sites
      in the chromosomal lacZ gene at frequencies up to 98% without selection. Our
      findings provide insight into modes of DNA target site recognition used by mobile
      group II introns. More generally, they show how the diversity of mobile group II
      introns can be exploited to provide a large variety of different target
      specificities and potentially other useful properties for gene targeting.

PMID- 19155323
TI  - Small molecule activators of pre-mRNA 3' cleavage.
AB  - 3' Cleavage and polyadenylation are obligatory steps in the biogenesis of most
      mammalian pre-mRNAs. In vitro reconstitution of the 3' cleavage reaction from
      human cleavage factors requires high concentrations of creatine phosphate (CP),
      though how CP activates cleavage is not known. Previously, we proposed that CP
      might work by competitively inhibiting a cleavage-suppressing serine/threonine
      (S/T) phosphatase. Here we show that fluoride/EDTA, a general S/T phosphatase
      inhibitor, activates in vitro cleavage in place of CP. Subsequent testing of
      inhibitors specific for different S/T phosphatases showed that inhibitors of the
      PPM family of S/T phosphatases, which includes PP2C, but not the PPP family,
      which includes PP1, PP2A, and PP2B, activated 3' cleavage in vitro. In
      particular, NCI 83633, an inhibitor of PP2C, activated extensive 3' cleavage at a
      concentration 50-fold below that required by fluoride or CP. The testing of
      structural analogs led to the identification of a more potent compound that
      activated 3' cleavage at 200 microM. While testing CP analogs to understand the
      origin of its cleavage activation effect, we found phosphocholine to be a more
      effective activator than CP. The minimal structural determinants of 3' cleavage
      activation by phosphocholine were identified. Our results describe a much
      improved small molecule activator of in vitro pre-mRNA cleavage, identify the
      molecular determinants of cleavage activation by phosphoamines such as
      phosphocholine, and suggest that a PPM family phosphatase is involved in the
      negative regulation of mammalian pre-mRNA 3' cleavage.

PMID- 19155324
TI  - Characterization of a heat-stable enzyme possessing GTP-dependent RNA ligase
      activity from a hyperthermophilic archaeon, Pyrococcus furiosus.
AB  - Using an expression protein library of a hyperthermophilic archaeon, Pyrococcus
      furiosus, we identified a gene (PF0027) that encodes a protein with heat-stable
      cyclic nucleotide phosphodiesterase (CPDase) activity. The PF0027 gene encoded a
      21-kDa protein and an amino acid sequence that showed approximately 27% identity
      to that of the 2'-5' tRNA ligase protein, ligT (20 kDa), from Escherichia coli.
      We found that the purified PF0027 protein possessed GTP-dependent RNA ligase
      activity and that synthetic tRNA halves bearing 2',3'-cyclic phosphate and 5'-OH
      termini were substrates for the ligation reaction in vitro. GTP hydrolysis was
      not required for the reaction, and GTPgammaS enhanced the tRNA ligation activity
      of PF0027 protein, suggesting that the ligation step is regulated by a novel
      mechanism. In comparison to the strong CPDase activity of the PF0027 protein, the
      RNA ligase activity itself was quite weak, and the ligation product was unstable
      during in vitro reaction. Finally, we used NMR to determine the solution
      structure of the PF0027 protein and discuss the implications of our results in
      understanding the role of the PF0027 protein.

PMID- 19155325
TI  - Knockdown of SLBP results in nuclear retention of histone mRNA.
AB  - Histone mRNAs are the only eukaryotic cellular mRNAs that are not polyadenylated.
      Synthesis of mature histone mRNA requires only a single processing reaction: an
      endonucleolytic cleavage between a conserved stem-loop and a purine-rich
      downstream element to form the 3' end. The stem-loop binding protein (SLBP) is
      required for processing, and following processing, histone mRNA is transported to
      the cytoplasm, where SLBP participates in translation of the histone mRNA and is
      also involved in regulation of histone mRNA degradation. Here we present an
      analysis of histone mRNA metabolism in cells with highly reduced levels of SLBP
      using RNA interference. Knocking down SLBP in U2OS cells results in a reduction
      in the rate of cell growth and an accumulation of cells in S-phase. Surprisingly,
      there is only a modest (twofold) decrease in histone mRNA levels. Much of histone
      mRNA in the SLBP knockdown cells is properly processed but is retained in the
      nucleus. The processed histone mRNA in SLBP knockdown cells is not rapidly
      degraded when DNA replication is inhibited. These results suggest a previously
      undescribed role for SLBP in histone mRNA export.

PMID- 19155326
TI  - A dominant mutation in DCL1 suppresses the hyl1 mutant phenotype by promoting the
      processing of miRNA.
AB  - MicroRNAs (miRNAs) are sequence-specific negative regulators of gene expression
      generated by DICER-LIKE1 (DCL1) with the assistance of a double-stranded RNA
      binding protein, HYPONASTIC LEAVES1 (HYL1), in Arabidopsis. To achieve a better
      understanding of miRNA biogenesis, we isolated hyl1 suppressors. Our genetic
      screening identified a novel semidominant mutation in DCL1 (dcl1-13), which
      causes an amino acid substitution of Glu-395 with Lys in the ATPase/DExH-box RNA
      helicase domain. This mutation confers significant restoration from the
      developmental abnormality and a reduction in the level of miRNA in the loss-of
      function mutant of HYL1. However, the dcl1-13 single mutant, exhibiting a
      decreased number of leaves, showed a slight decrease in miRNA accumulation. Thus,
      the effect of the dcl1-13 mutation is HYL1 dependent: it promotes miRNA
      processing in the absence of HYL1, but conversely, impairs it in the presence of
      HYL1. Our results suggest significant roles of the helicase domain of DCL1, which
      remain unclear to date, possibly in relation with HYL1.

PMID- 19155327
TI  - Splicing of designer exons reveals unexpected complexity in pre-mRNA splicing.
AB  - Pre-messengerRNA (mRNA) splicing requires the accurate recognition of splice
      sites by the cellular RNA processing machinery. In addition to sequences that
      comprise the branchpoint and the 3' and 5' splice sites, the cellular splicing
      machinery relies on additional information in the form of exonic and intronic
      splicing enhancer and silencer sequences. The high abundance of these motifs
      makes it difficult to investigate their effects using standard genetic
      perturbations, since their disruption often leads to the formation of yet new
      elements. To lessen this problem, we have designed synthetic exons comprised of
      multiple copies of a single prototypical exonic enhancer and a single
      prototypical exonic silencer sequence separated by neutral spacer sequences. The
      spacer sequences buffer the exon against the formation of new elements as the
      number and order of the original elements are varied. Over 100 such designer
      exons were constructed by random ligation of enhancer, silencer, and neutral
      elements. Each exon was positioned as the central exon in a 3-exon minigene and
      tested for exon inclusion after transient transfection. The level of inclusion of
      the test exons was seen to be dependent on the provision of enhancers and could
      be decreased by the provision of silencers. In general, there was a good
      quantitative correlation between the proportion of enhancers and splicing.
      However, widely varying inclusion levels could be produced by different
      permutations of the enhancer and silencer elements, indicating that even in this
      simplified system splicing decisions rest on complex interplays of yet to be
      determined parameters.

PMID- 19155328
TI  - Specific roles for the Ccr4-Not complex subunits in expression of the genome.
AB  - In this work we used micro-array experiments to determine the role of each
      nonessential subunit of the conserved Ccr4-Not complex in the control of gene
      expression in the yeast Saccharomyces cerevisiae. The study was performed with
      cells growing exponentially in high glucose and with cells grown to glucose
      depletion. Specific patterns of gene deregulation were observed upon deletion of
      any given subunit, revealing the specificity of each subunit's function.
      Consistently, the purification of the Ccr4-Not complex through Caf40p by tandem
      affinity purification from wild-type cells or cells lacking individual subunits
      of the Ccr4-Not complex revealed that each subunit had a particular impact on
      complex integrity. Furthermore, the micro-arrays revealed that the role of each
      subunit was specific to the growth conditions. From the study of only two
      different growth conditions, revealing an impact of the Ccr4-Not complex on more
      than 85% of all studied genes, we can infer that the Ccr4-Not complex is
      important for expression of most of the yeast genome.

PMID- 19155329
TI  - Phosphorylation of FMRP inhibits association with Dicer.
AB  - Fragile X syndrome is caused by an absence of the protein product of the fragile
      X mental retardation gene (FMR1). The fragile X mental retardation protein (FMRP)
      is an RNA-binding protein that regulates translation of associated mRNAs;
      however, the mechanism for this regulation remains unknown. Constitutively,
      phosphorylated FMRP (P-FMRP) is found associated with stalled untranslating
      polyribosomes, and translation of at least one mRNA is down-regulated when FMRP
      is phosphorylated. Based on our hypothesis that translational regulation by P
      FMRP is accomplished through association with the microRNA (miRNA) pathway, we
      developed a phospho-specific antibody to P-FMRP and showed that P-FMRP associates
      with increased amounts of precursor miRNAs (pre-miRNA) compared with total FMRP.
      Furthermore, P-FMRP does not associate with Dicer or Dicer-containing complexes
      in coimmunoprecipitation experiments or in an in vitro capture assay using a P
      FMRP peptide sequence bound to agarose beads. These data show that Dicer
      containing complexes bind FMRP at amino acids 496-503 and that phosphorylation
      disrupts this association with a consequent increase in association with pre
      miRNAs. In sum, we propose that in addition to regulating translation,
      phosphorylation of FMRP regulates its association with the miRNA pathway by
      modulating association with Dicer.

PMID- 19155331
TI  - The effect of selenium, as selenomethionine, on genome stability and cytotoxicity
      in human lymphocytes measured using the cytokinesis-block micronucleus cytome
      assay.
AB  - A supranutritional intake of selenium (Se) may be required for cancer prevention,
      but an excessively high dose could be toxic. Therefore, the effect on genome
      stability of seleno-L-methionine (Se-met), the most important dietary form of Se,
      was measured to determine its bioefficacy and safety limit. Peripheral blood
      lymphocytes were isolated from six volunteers and cultured with medium
      supplemented with Se-met in a series of Se concentrations (3, 31, 125, 430, 1880
      and 3850 microg Se/litre) while keeping the total methionine (i.e. Se-met + L
      methionine) concentration constant at 50 microM. Baseline genome stability of
      lymphocytes and the extent of DNA damage induced by 1.5-Gy gamma-ray were
      investigated using the cytokinesis-block micronucleus cytome assay after 9 days
      of culture in 96-microwell plates. High Se concentrations (>or=1880 microg
      Se/litre) caused strong inhibition of cell division and increased cell death (P <
      0.0001). Baseline frequency of nucleoplasmic bridges and nuclear buds, however,
      declined significantly (P trend < 0.05) as Se concentration increased from 3 to
      430 microg Se/litre. Se concentration (<or=430 microg Se/litre) had no
      significant effect on baseline frequency of micronuclei and had no protective
      effect against genome damage induced by exposure to 1.5-Gy gamma-ray irradiation.
      In conclusion, Se, as Se-met, may improve genome stability at concentrations up
      to 430 microg Se/litre, but higher doses may be cytotoxic. Therefore, a cautious
      approach to supplementation with Se-met is required to ensure that optimal genome
      health is achieved without cytotoxic effects.

PMID- 19155330
TI  - Neighborhood psychosocial hazards and the association of cumulative lead dose
      with cognitive function in older adults.
AB  - Before the 1970s, today's older Americans were exposed to high levels of lead in
      the environment. The authors previously reported that lifetime cumulative lead
      dose was associated with lower cognitive test performance in older adults.
      Experiments suggest that environmental stress may intensify the detrimental
      influence of lead. No large, population-based studies of this question have been
      done. The authors evaluated whether cross-sectional associations of tibia lead
      with cognitive function were modified by neighborhood psychosocial hazards in the
      Baltimore Memory Study (2001-2005), a longitudinal cohort study of determinants
      of cognitive decline. Tibia lead was measured via (109)Cd-induced K-shell X-ray
      fluorescence. Neighborhood psychosocial hazards were measured independently of
      study subjects. Complete data were available among 1,001 demographically diverse
      adults aged 50-70 years, randomly selected from 65 contiguous neighborhoods in
      Baltimore City. Hierarchical mixed-effects regression models showed that
      neighborhood psychosocial hazards exacerbated the adverse associations of tibia
      lead in 3 of 7 cognitive domains after adjustment for age, sex, race/ethnicity,
      education, testing technician, and time of day (language, P = 0.039; processing
      speed, P = 0.067; executive functioning, P = 0.025). The joint occurrence of
      environmental stress and lead exposure across the life span may partially explain
      persistent racial/ethnic and socioeconomic disparities in cognitive function in
      late life.

PMID- 19155332
TI  - Effects of disulfide bond reducing agents on sperm chromatin structural integrity
      and developmental competence of in vitro matured oocytes after intracytoplasmic
      sperm injection in pigs.
AB  - We recently reported that electrical activation followed by secondary chemical
      activation greatly enhanced the developmental competence of in vitro matured
      porcine oocytes fertilized by intracytoplasmic sperm injection (ICSI). We
      hypothesized that sperm treatment with disulfide bond reducing agents will
      enhance the development competence of porcine embryos produced by this ICSI
      procedure. We examined the effects of glutathione (GSH), dithiothreitol (DTT),
      GSH or DTT in combination with heparin on sperm DNA structure, paternal
      chromosomal integrity, pronuclear formation, and developmental competence of in
      vitro matured porcine oocytes after ICSI. Acridine orange staining and flow
      cytometry based sperm chromatin structure assay were used to determine sperm DNA
      integrity by calculating the cells outside the main population (COMP alphaT). No
      differences were observed in COMP alphaT values among GSH-treated and control
      groups. COMP alphaT values in GSH-treated groups were significantly lower than
      that in DTT-treated groups. Following ICSI, GSH treatments did not significantly
      alter paternal chromosomal integrity. Paternal chromosomal integrity in sperm
      treated with DTT plus or minus heparin was also the lowest among all groups. GSH
      treated sperm yielded the highest rates of normal fertilization and blastocyst
      formation, which were significantly higher than that of control and DTT-treated
      groups. The majority of blastocysts derived from control and GSH-treated
      spermatozoa were diploid, whereas blastocysts derived from DTT-treated
      spermatozoa were haploid. In conclusion, sperm treatment with GSH enhanced the
      developmental capacity of porcine embryos produced by our optimized ICSI
      procedure.

PMID- 19155333
TI  - Crossectomy and foam: has it got a role in the contemporary management of primary
      varicose veins?

PMID- 19155334
TI  - Venous haemodynamics: what we know and don't know.
AB  - The presence of haemodynamic abnormalities in chronic venous disease (CVD) has
      been well established. The relationships between these abnormalities and clinical
      manifestations, or natural history of CVD, are complex and remain to be
      investigated. Flow-mediated processes and mechanisms unrelated to blood flow may
      play an important role in the pathophysiology of CVD. Current state of knowledge
      makes questionable a possibility of building treatment strategies based on a
      single simplified model of the disease. As an example of such simplified
      approach, CHIVA introduces an opportunity to critically assess the gaps in
      knowledge in venous pathophysiology.

PMID- 19155335
TI  - Meta-analysis of subfascial endoscopic perforator vein surgery (SEPS) for chronic
      venous insufficiency.
AB  - OBJECTIVES: The degree of benefits and risks, and the role of subfascial
      endoscopic perforator vein surgery (SEPS) in the management for chronic venous
      insufficiency (CVI) remains uncertain. METHODS: A multiple health database search
      was performed including Medline, Embase, Ovid, Cochrane Database of Systematic
      Reviews, and Cochrane Database of Abstracts of Reviews of Effectiveness, on all
      studies published between 1985 and 2008 that reported on health outcomes in
      patients with CVI treated with SEPS and comparing this therapy with the
      conventional Linton procedure. Three studies, which compared SEPS with
      conventional surgery, were included in the present meta-analysis. RESULTS:
      Between SEPS and Linton groups, there was a significant lower rate of wound
      infections for SEPS (odds ratio [OR] 0.06 [95% confidence interval (CI) 0.02 to
      0.25]) and a significantly reduced hospital stay for SEPS (OR -8.96 [95% CI 
      11.62 to -6.30]). In addition, SEPS was associated with a significant reduced
      rate of recurrent ulcers (mean follow-up 21 months) (OR 0.15 [95% CI 0.04-0.62]).
      There was no significant difference between the groups in the following
      dimensions: rate of hospital re-admission (OR 0.21 [95% CI 0.03-1.31]), death at
      six months (OR 3.00 [95% CI 0.11-78.27]), ulcer healing rate at four months (OR
      0.44 [95% CI 0.09-2.12]), and the rate of deep vein thrombosis (DVT) (OR 0.35
      [95% CI 0.01-8.85]). CONCLUSION: From the level of evidence available by now it
      seems that SEPS, used as a part of a treatment regimen for severe CVI, benefits
      most patients in the short term regarding ulcer healing and the prevention of
      ulcer recurrence. It can be safely performed with less early postoperative
      complications compared with the Linton procedure. However, further prospective
      randomized trials are required to define the long-term benefits of SEPS.

PMID- 19155336
TI  - The clinical significance of below-knee great saphenous vein reflux following
      endovenous laser ablation of above-knee great saphenous vein.
AB  - AIMS: The standard technique for endovenous laser ablation (EVLA) for varicose
      veins due to great saphenous vein (GSV) reflux involves obliteration of the above
      knee (AK) GSV. This study assesses the significance of persistent below-knee (BK)
      GSV reflux following such therapy. METHODS: Sixty-nine limbs (64 patients) with
      varicosities and GSV reflux underwent AK-EVLA. Post treatment, GSV reflux
      (ultrasound: six, 12 weeks) and Aberdeen varicose vein severity scores (AVVSS, 12
      weeks) were assessed, and residual varicosities treated with foam sclerotherapy
      (six weeks). RESULTS: The untreated BK-GSV remained patent in all limbs.
      Ultrasound showed normal antegrade flow in 34/69 (49%, Group A), flash reflux<1 s
      in 7/69 (10%, Group B) and >1 s reflux in 28/69 (41%, Group C). Although AVVSS
      improved in all groups (P<0.001): A: 14.6 (8.4-19.3) versus 2.8 (0.5-4.4), B:
      13.9 (7.5-20.1) versus 3.7 (2.1-6.8), C: 15.1 (8.9-22.5) versus 8.1 (5.3-12.6)
      the improvement was less in Group C (P<0.001 versus A and B) and was associated
      with a greater requirement (A: 4/34 [12%]; B: 1/7 [14%]; C: 25/28 [89%]) for
      sclerotherapy (persisting varicosities) (P<0.001). CONCLUSION: Although AK-GSV
      EVLA improves symptoms regardless of persisting BK reflux, the latter appears
      responsible for residual symptoms and a greater need for sclerotherapy for
      residual varicosities.

PMID- 19155337
TI  - Rate of occupational leg swelling is greater in the morning than in the
      afternoon.
AB  - The aim of this study was to investigate the rate of occupational leg swelling
      depending on the time period of the working day. Volumetric variations of the
      legs of 70 hospital employees, enrolled in three groups, were evaluated. Group I:
      35 morning shift workers; Group II: 35 afternoon shift workers; and Group III: 15
      individuals randomly selected from Groups I and II, who were evaluated on the day
      they worked 12 hours consecutively. Volumetry was performed before and after each
      shift for both legs of the participants in Groups I and II. For Group III
      volumetry was performed early in the morning, at noon and in the evening. For
      statistical analysis, the Student's t-test and Mann-Whitney test were used with
      an alpha error of 5% being considered acceptable (P value<0.05). Significant
      increases in volume were recorded for the limbs in all three groups (P
      value<0.001). On comparing Groups I and II, the accumulation of fluids was
      significantly higher in the morning than in the afternoon (P value<0.003).
      Asymptomatic workers may present with oedema of the legs during their work with
      the rate of oedema being different for morning and afternoon shifts. The
      possibility of wearing compression stockings should be considered for this type
      of work.

PMID- 19155338
TI  - First results with a new 1470-nm diode laser for endovenous ablation of
      incompetent saphenous veins.
AB  - INTRODUCTION: Most of the published EVLA data concern 810, 940, 980 nm diode
      lasers and 1064 or 1320 nm Nd:Yag laser systems. Major side effects are
      postoperative pain and bruising. The aim of this study was to show the outcome
      one year after EVLA of incompetent saphenous veins with a 1470 nm Diode laser
      (Ceralas E, biolitec). PATIENTS AND METHOD: Between December 2006 and February
      2007, 134 saphenous veins (108 GSV, 26 SSV) in 117 legs of 100 consecutive
      patients where treated by EVLA for GSV and SSV incompetence. All patients were
      examined clinically and with duplex by an experienced phlebologist prior to
      intervention, and at the follow-up visits for complications, occlusion, flow and
      reflux in the treated vein segment. The clinical evaluation included clinical
      CEAP and the presence of recurrent varicose veins. Patient satisfaction was
      assessed by a 0 to 4 scale. RESULTS: After a mean follow-up period of 184 days
      (SD 27) 127 treated veins (102 GSV, 25 SSV) of 111 limbs in 94 patients and after
      329 days (SD 14) 105 treated veins (94 GSV, 21 SSV) of 105 limbs in 83 patients
      were reinvestigated. Six patients were lost to follow up after six months and an
      additional 11 patients after one year. Up to one year follow-up all treated veins
      remained occluded. At six months, one new insufficient anterior accessory
      saphenous vein (AASV) and after 12 months, three new insufficient AASV occurred.
      After one year 45 patients were very satisfied with the method, 34 were
      satisfied, three were fairly and one was not satisfied. The mean of all answers
      was 0.5 (SD 0.5). In three cases phlebitic reactions after 10 days, but no severe
      complications such as deep vein thrombosis occured. After six months in 9.5% of
      the legs paresthesia was present in the treated area which reduced to 7.6% after
      one year. Intake of painkillers was mean 6.7 tablets (SD 3.5). When we compared
      GSV legs treated with LEED below or above 100 J/cm, the paresthesia rate was
      significantly lower in the first group with 2.3% compared to 15.5 % in the higher
      LEED group. The differences for number of days with analgesic intake and for the
      paraesthetic area were significant. Discussion In this prospective follow-up
      study with 100 consecutive patients and 134 treated saphenous veins a high
      occlusion rate of 100% could be demonstrated one year after treatment. However,
      with LEED > 100 J/cm in this study, the incidence of paresthesia rose
      significantly. Therefore it seems adequate to stay below 100 J/cm in the future
      as the occlusion rate was the same below and above 100 J/cm. CONCLUSION: EVLA of
      GSV and SSV with a 1470 nm diode laser is a minimally invasive, safe and
      efficient therapy option with a high success rate.

PMID- 19155339
TI  - Changes in the pressure and the dynamic stiffness index of medical elastic
      compression stockings after having been worn for eight hours: a pilot study.
AB  - OBJECTIVES: There is no data available at present on the changes in the exerted
      pressure together with the dynamic stiffness index (DSI) of medical elastic
      compression stockings (MECS). The objective of this pilot study was to measure
      the pressure and calculate the DSI of 12 different brands of MECS before and
      after having been worn for eight hours. METHODS: In all, 12 different
      commercially available brands of MECS that were divided into two categories
      (class I round-knitted and class II flat-knitted MECS) were tested. The pressure
      was measured, and the DSI of the MECS was first calculated at the B1 level before
      wearing in the morning and again eight hours after they had been worn. All
      laboratory measurements were performed using a newly developed dynamic leg
      segment model. RESULTS: The pressure at the B1 level dropped significantly in all
      12 brands of MECS after having been worn for eight hours, whereas the DSI
      remained unchanged. CONCLUSION: The DSI of MECS reflects an important and
      particularly consistent therapeutic effect. As the pressure drops during the day,
      the pressure amplitude or pulsations remain the same. The pressure drop may be
      due to fatigue of the elastic material. The DSI would therefore form a valuable
      indicator for prescribing the most effective MECS for the patient.

PMID- 19155340
TI  - Surgery in patients with vascular malformations of the head and neck: value of
      coagulation disorders.
AB  - OBJECTIVES: The surgical treatment of congenital vascular malformations always
      bears the risk of severe bleeding. The aim of this study was to investigate the
      prevalence of haemostatic abnormalities in patients with congenital vascular
      malformations of the head and neck which could additionally complicate the
      complex surgery of vascular malformations. METHODS: Thirteen patients with
      congenital vascular malformations of the head and neck, who underwent scheduled
      surgery, were reviewed regarding their haemostatic tests, including prothrombin
      time, activated partial thromboplastin time, fibrinogen level, platelet count,
      platelet function analyzer-epinephrine (PFA-Epi) and -adenosine diphosphate (ADP)
      (PFA-100), von Willebrand factor (vWF) and D-dimers. RESULTS: In six of 13
      patients an impaired primary haemostasis was detected by prolonged PFA-Epi and
      one of these patients also had a slightly prolonged PFA-ADP. Additionally, two of
      the patients showed mild coagulation factor deficiency. One patient had a mild
      vWF deficiency that was not detected by PFA-100. CONCLUSION: Prior to surgery of
      congenital vascular malformations of the head and neck, a detailed coagulation
      analysis is needed in order to identify those patients at increased risk of
      bleeding. This proceeding is supported by the fact that a relevant portion of the
      patients with congenital vascular malformations of the head and neck show an
      impaired primary haemostasis.

PMID- 19155341
TI  - Varicose vein surgery performed by a surgical care practitioner.
AB  - A surgical care practitioner (SCP) completed a structured training programme to
      perform all aspects of varicose vein surgery including sapheno-femoral
      disconnection and long saphenous vein stripping. Over a four-year period, she
      performed 152 groin procedures, closed 191 groin wounds and undertook
      phlebectomies on 91 legs with excellent results. A SCP can be used to improve
      theatre utilization and efficiency with no obvious drawbacks.

PMID- 19155342
TI  - Echo-guided foam sclerotherapy treatment of venous malformation involving the
      sciatic nerve.
AB  - Primary sciatic nerve varices (SNV) lie within the sciatic nerve possibly causing
      chronic venous disease and sciatic pain as well. We report a series of 12
      consecutive patients affected by symptomatic SNV. All of them were treated by
      echo-guided Tessari foam sclerotherapy (EGFSCL). Mean follow up lasted two years.
      Reflux through the sciatic veins, as the connected superficial varicose veins,
      disappeared in the entire cohort and only minor complications have emerged.
      EGFSCL seems to be both safe and effective, so representing a reliable and
      minimally invasive treatment.

PMID- 19155343
TI  - Stigmatization as an environmental risk in schizophrenia: a user perspective.
AB  - Stigmatization represents a chronic negative interaction with the environment
      that most people with a diagnosis of schizophrenia face on a regular basis.
      Different types of stigma-public stigma, self--stigma, and label avoidance--may
      each have detrimental effects. In the present article, the possible consequences
      of stigma on onset, course, and outcome of schizophrenia are reviewed.
      Stigmatization may be conceptualized as a modifiable environmental risk factor
      that exerts its influence along a variety of different pathways, not only after
      the illness has been formally diagnosed but also before, on the basis of subtle
      behavioral expressions of schizophrenia liability. Integrating stigma-coping
      strategies in treatment may represent a cost-effective way to reduce the risk of
      relapse and poor outcome occasioned by chronic exposure to stigma. In addition,
      significant gains in quality of life may result if all patients with
      schizophrenia routinely receive information about stigma and are taught to use
      simple strategies to increase resilience vis-a-vis adverse, stigmatizing
      environments.

PMID- 19155344
TI  - Prenatal malnutrition and adult schizophrenia: further evidence from the 1959
      1961 Chinese famine.
AB  - OBJECTIVE: Evidence from the 1944-1995 Dutch Hunger Winter and the 1959-1961
      Chinese famines suggests that those conceived or in early gestation during
      famines, have a 2-fold increased risk of developing schizophrenia in adult life.
      We tested the hypothesis in a second Chinese population and also determined
      whether risk differed between urban and rural areas. METHOD: The risk of
      schizophrenia was examined in Liuzhou prefecture of Guangxi autonomous region.
      Rates were compared among those conceived before, during, and after the famine
      years. Based on the decline in birth rates, we predicted that those born in 1960
      and 1961 would have been exposed to the famine during conception or early
      gestation. All psychiatric case records in Liuzhou psychiatric hospital for the
      years 1971 through 2001 were examined and clinical/sociodemographic data
      extracted by psychiatrists blind to exposure status. Data on births and deaths in
      the famine years were also available, and cumulative mortality was estimated from
      later demographic surveys. Evidence of famine was verified, and results were
      adjusted for mortality. Relative risks (RRs) for schizophrenia were calculated
      for the region as a whole and for urban and rural areas separately. RESULTS:
      Mortality-adjusted RR for schizophrenia was 1.5 (1960) and 2.05 (1961),
      respectively. However, the effect was exclusively from the rural areas RR = 1.68
      (1960) and RR = 2.25 (1961). CONCLUSIONS: We observe a 2-fold increased risk of
      schizophrenia among those conceived or in early gestation at the height of famine
      with risk related to severity of famine conditions.

PMID- 19155346
TI  - Human papillomavirus vaccine safety in pediatric patients: an evaluation of the
      Vaccine Adverse Event Reporting System.
AB  - Recent news reports have linked the human papillomavirus (HPV) vaccine to serious
      adverse events (AEs) in children and adolescents. We used the Vaccine Adverse
      Event Reporting System (VAERS) database to extract postmarketing AEs reported in
      patients who received the vaccine. Since approval of the HPV vaccine in the US,
      3174 AEs occurring in children and adolescents (aged 6-17 y) have been reported
      to the VAERS. Of these, 191 (6%) were deemed to be serious. Although these AEs
      are of significant concern, more research is required before they can be directly
      correlated with the vaccine.

PMID- 19155347
TI  - Publication metrics and record of pharmacy practice chairs.
AB  - BACKGROUND: Scholarship is an essential component of academic pharmacy.
      Department chairs are considered role models and mentors to junior faculty, but
      their publication record has not been documented. OBJECTIVE: To quantify
      publication patterns of pharmacy practice chairs in general and, specifically, at
      health sciences center (HSC)-based versus non-HSC-based and public versus private
      colleges of pharmacy. METHODS: Pharmacy practice chairs were identified using the
      2006-2007 roster of faculty from the American Association of Colleges of
      Pharmacy. Of the 89 colleges of pharmacy in the roster, 11 listed no pharmacy
      practice chair and 5 listed more than one. Data were collected on the remaining
      73 schools by searching each chair's name on PubMed and Web of Science (WoS).
      Data on total publications, publications per year, total citations, citations per
      article, h-index, and m quotient were collected. RESULTS: A total of 2394 papers
      published by 73 pharmacy practice chairs were found in a search of PubMed. The
      mean number of total publications per chair was 33 (95% CI 21 to 44). The mean
      number of publications per year was 1.4 using PubMed and 1.6 using WoS. Mean h
      index was 8.0 (95% CI 6.3 to 9.6). Mean number of total citations was 410 (95% CI
      252 to 568). Thirty-three percent (n = 24) had less than 10 lifetime publications
      and 18% had more than 50 lifetime publications. HSC-based chairs averaged 51.3
      papers while non-HSC-based chairs averaged 19.1 (p < 0.01). Similar data were
      found for total citations (HSC = 673 vs non-HSC = 216; p < 0.001). Public school
      chairs had an average of 41.5 articles cited on PubMed, versus 15 for private
      school chairs (p < 0.01). Public school chairs had an average h-index of 9.7
      versus 4.4 for private school chairs (p < 0.001), and an average of 9.2 citations
      per article compared with 5.2 for private school chairs (p < 0.001). CONCLUSIONS:
      These data provide a normative pattern of publication metrics and record for
      pharmacy practice chairs and demonstrate marked variability in scholarly
      productivity.

PMID- 19155345
TI  - Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of
      self-monitoring.
AB  - Over the last 2 decades, a large number of neurophysiological and neuroimaging
      studies of patients with schizophrenia have furnished in vivo evidence for
      dysconnectivity, ie, abnormal functional integration of brain processes. While
      the evidence for dysconnectivity in schizophrenia is strong, its etiology,
      pathophysiological mechanisms, and significance for clinical symptoms are
      unclear. First, dysconnectivity could result from aberrant wiring of connections
      during development, from aberrant synaptic plasticity, or from both. Second, it
      is not clear how schizophrenic symptoms can be understood mechanistically as a
      consequence of dysconnectivity. Third, if dysconnectivity is the primary
      pathophysiology, and not just an epiphenomenon, then it should provide a
      mechanistic explanation for known empirical facts about schizophrenia. This
      article addresses these 3 issues in the framework of the dysconnection
      hypothesis. This theory postulates that the core pathology in schizophrenia
      resides in aberrant N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic
      plasticity due to abnormal regulation of NMDARs by neuromodulatory transmitters
      like dopamine, serotonin, or acetylcholine. We argue that this neurobiological
      mechanism can explain failures of self-monitoring, leading to a mechanistic
      explanation for first-rank symptoms as pathognomonic features of schizophrenia,
      and may provide a basis for future diagnostic classifications with
      physiologically defined patient subgroups. Finally, we test the explanatory power
      of our theory against a list of empirical facts about schizophrenia.

PMID- 19155348
TI  - Repression of seed maturation genes by a trihelix transcriptional repressor in
      Arabidopsis seedlings.
AB  - The seed maturation program is repressed during germination and seedling
      development so that embryonic genes are not expressed in vegetative organs. Here,
      we describe a regulator that represses the expression of embryonic seed
      maturation genes in vegetative tissues. ASIL1 (for Arabidopsis 6b-interacting
      protein 1-like 1) was isolated by its interaction with the Arabidopsis thaliana
      2S3 promoter. ASIL1 possesses domains conserved in the plant-specific trihelix
      family of DNA binding proteins and belongs to a subfamily of 6b-interacting
      protein 1-like factors. The seedlings of asil1 mutants exhibited a global shift
      in gene expression to a profile resembling late embryogenesis. LEAFY COTYLEDON1
      and 2 were markedly derepressed during early germination, as was a large subset
      of seed maturation genes, such as those encoding seed storage proteins and
      oleosins, in seedlings of asil1 mutants. Consistent with this, asil1 seedlings
      accumulated 2S albumin and oil with a fatty acid composition similar to that of
      seed-derived lipid. Moreover, ASIL1 specifically recognized a GT element that
      overlaps the G-box and is in close proximity to the RY repeats of the 2S
      promoters. We suggest that ASIL1 targets GT-box-containing embryonic genes by
      competing with the binding of transcriptional activators to this promoter region.

PMID- 19155349
TI  - A novel pathway for sesquiterpene biosynthesis from Z,Z-farnesyl pyrophosphate in
      the wild tomato Solanum habrochaites.
AB  - In the wild tomato Solanum habrochaites, the Sst2 locus on chromosome 8 is
      responsible for the biosynthesis of several class II sesquiterpene olefins by
      glandular trichomes. Analysis of a trichome-specific EST collection from S.
      habrochaites revealed two candidate genes for the synthesis of Sst2-associated
      sesquiterpenes. zFPS encodes a protein with homology to Z-isoprenyl pyrophosphate
      synthases and SBS (for Santalene and Bergamotene Synthase) encodes a terpene
      synthase with homology to kaurene synthases. Both genes were found to cosegregate
      with the Sst2 locus. Recombinant zFPS protein catalyzed the synthesis of Z,Z-FPP
      from isopentenylpyrophosphate (IPP) and dimethylallylpyrophosphate (DMAPP), while
      coincubation of zFPS and SBS with the same substrates yielded a mixture of
      olefins identical to the Sst2-associated sesquiterpenes, including (+)-alpha
      santalene, (+)-endo-beta-bergamotene, and (-)-endo-alpha-bergamotene. In
      addition, headspace analysis of tobacco (Nicotiana sylvestris) plants expressing
      zFPS and SBS in glandular trichomes afforded the same mix of sesquiterpenes. Each
      of these proteins contains a putative plastid targeting sequence that mediates
      transport of a fused green fluorescent protein to the chloroplasts, suggesting
      that the biosynthesis of these sesquiterpenes uses IPP and DMAPP from the
      plastidic DXP pathway. These results provide novel insights into sesquiterpene
      biosynthesis and have general implications concerning sesquiterpene engineering
      in plants.

PMID- 19155350
TI  - Cortical plasticity following motor skill learning during mental practice in
      stroke.
AB  - BACKGROUND: and purpose. Mental practice (MP), which involves cognitive rehearsal
      of physical movements, is a noninvasive, inexpensive method of enabling
      repetitive, task-specific practice (RTP). Recent, randomized controlled data
      suggest that MP, when combined with an RTP therapy program, increases affected
      arm use and function significantly more than RTP only. As a next step, this 10
      subject case series examined the possibility that cortical plasticity is a
      mechanism underlying the treatment effect of MP when combined with RTP. METHOD:
      Ten chronic stroke patients (mean = 36.7 months) exhibiting stable, moderate
      motor deficits received 30-minute therapy sessions for their affected arms,
      occurring 3 days/week for 10 weeks, and emphasizing valued activities of daily
      living (ADLs). Directly after therapy, subjects received 30-minute MP sessions,
      which required MP of the ADLs performed during therapy. Behavioral outcomes were
      blindly evaluated using the Action Research Arm Test (ARAT) and the Fugl-Meyer
      Assessment (FM). Functional magnetic resonance imaging (fMRI) was administered
      before and after intervention to assess cortical changes. RESULTS: Before
      intervention, subjects exhibited stable motor deficits. After intervention,
      subjects exhibited ARAT and FM score increases (+5.3 and +4.2, respectively) and
      clinically significant gains in ADLs. Postintervention fMRI revealed significant
      increases in activation to wrist flexion and extension of the affected hand in
      the premotor area and primary motor cortex ipsilateral and contralateral to the
      affected hand, as well as in superior parietal cortex ipsilateral to the affected
      hand. Decreased activation was noted in parietal cortex of the hemisphere
      ipsilateral to the affected hand. These changes correlated with anatomical
      regions in which behavioral changes were observed in the ARAT and FM.
      CONCLUSIONS: MP is an easy to use, cost-effective strategy that was again shown
      to improve affected arm outcomes after stroke. This is the first study to
      demonstrate alteration in the cortical map in response to MP training.

PMID- 19155352
TI  - Sleep apnea and family physicians.

PMID- 19155351
TI  - Intramuscular electrical stimulation for upper limb recovery in chronic
      hemiparesis: an exploratory randomized clinical trial.
AB  - BACKGROUND: Surface electrical stimulation (ES) has been shown to improve the
      motor impairment of stroke survivors. However, surface ES can be painful and
      motor activation can be inconsistent from session to session. Percutaneous
      intramuscular ES may be an effective alternative. OBJECTIVE: Evaluate the
      effectiveness of percutaneous intramuscular ES in facilitating the recovery of
      the hemiparetic upper limb of chronic stroke survivors. METHODS: A total of 26
      chronic stroke survivors were randomly assigned to percutaneous intramuscular ES
      for hand opening (n = 13) or percutaneous ES for sensory stimulation only (n =
      13). The intramuscular ES group received cyclic, electromyography (EMG)-triggered
      or EMG-controlled ES depending on baseline motor status. All participants
      received 1 hour of stimulation per day for 6 weeks. After completion of ES,
      participants received 18 hours of task-specific functional training. The primary
      outcome measure was the Fugl-Meyer Motor Assessment. Secondary measures included
      the Arm Motor Ability Test and delay and termination of EMG activity. Outcomes
      were assessed in a blinded manner at baseline, at the end of ES, at the end of
      functional training, and at 1, 3, and 6 months follow-up. RESULTS: Repeated
      measure analysis of variance did not yield any significant treatment, or time by
      treatment interaction effects for any of the outcome measures. CONCLUSION:
      Percutaneous intramuscular ES does not appear to be any more effective than
      sensory ES in enhancing the recovery of the hemiparetic upper limb among chronic
      stroke survivors. However, because of the exploratory nature of the study and its
      inherent limitations, conclusions must be drawn with caution.

PMID- 19155354
TI  - Antibiotics in acute exacerbations of chronic obstructive pulmonary disease.

PMID- 19155355
TI  - Bless me, for I have sinned ...: Behaviour change and the confessional.

PMID- 19155357
TI  - Rebuttal: Do nurse practitioners pose a threat to family physicians?: NO.

PMID- 19155358
TI  - Rebuttal: Do nurse practitioners pose a threat to family physicians?: YES.

PMID- 19155361
TI  - Punch biopsy of pigmented lesions is potentially hazardous.

PMID- 19155362
TI  - Approach to inflammatory breast cancer.
AB  - OBJECTIVE: To review the definition, clinical presentation, and management of
      inflammatory breast cancer in primary care. SOURCES OF INFORMATION: Relevant
      research and review articles, as well as personal experience of the authors
      practising in a specialized locally advanced breast cancer program at a
      comprehensive cancer centre. Evidence is levels II and III. MAIN MESSAGE:
      Inflammatory breast cancer is a rare disease that typically presents with a
      rapidly enlarging erythematous breast, often with no discernable breast mass.
      Identification of warning signs and recognition of clinical symptoms are crucial
      to prompt diagnosis and appropriate referral. Management in the primary care
      setting includes treatment of symptoms, psychosocial support, regular
      surveillance and follow-up, as well as palliative care. CONCLUSION: Family
      physicians are usually the entry point to the health care system and are well
      positioned to assess inflammation of the breast and recognize the warning signs
      of an underlying inflammatory breast cancer. They are also important members of
      the team that provides support for breast cancer patients and their families
      during treatment, follow-up, and end-of-life care.

PMID- 19155363
TI  - Role of radiology in geriatric care: a primer for family physicians.
AB  - OBJECTIVE: To present family physicians with the options available for diagnosing
      and treating a selection of common diseases in the elderly using diagnostic and
      interventional radiology. QUALITY OF EVIDENCE: Articles providing level I or II
      evidence were included in our review. Most articles presented results from
      randomized or other case-controlled studies. MAIN MESSAGE: Geriatric care has
      become a complicated, multidisciplinary effort, with the family physician often
      leading the team. The expanding cohort of patients is not only better informed
      than their predecessors, but also more demanding of better care through cutting
      edge technology and treatment. Specifically, the role of radiology has expanded
      quickly in geriatric medicine. Because of complex clinical presentations and
      rising costs, it is essential for primary care physicians to understand the
      appropriate use of imaging and radiological intervention. CONCLUSION: There are a
      number of new and innovative radiological techniques and procedures available for
      elderly patients. This review aims to inform primary care physicians of a
      selected number of these techniques.

PMID- 19155364
TI  - Update on the Canadian Diabetes Association 2008 clinical practice guidelines.

PMID- 19155365
TI  - Use of diuretics during pregnancy.
AB  - QUESTION: Several of my pregnant patients use diuretics for hypertension. I have
      heard that diuretics cannot be used in pregnancy because of the reduction of
      plasma volume and the potential for decreasing placental perfusion, as well as a
      possible diabetogenic effect. ANSWER: Many studies--including a meta-analysis of
      almost 7000 neonates exposed to diuretics during pregnancy--did not find an
      increased risk of adverse effects, such as birth defects, fetal growth
      restriction, thrombocytopenia, or diabetes, among neonates exposed to diuretics
      in utero.

PMID- 19155366
TI  - Should I stay or should I go?: toxic alcohol case in the emergency department.

PMID- 19155367
TI  - Complications of nonphysician-supervised laser hair removal: case report and
      literature review.

PMID- 19155368
TI  - Cryotherapy: minor surgery video series.

PMID- 19155369
TI  - Genetics: hereditary hemochromatosis.

PMID- 19155370
TI  - Question: Can you identify this condition? Tuberculoid leprosy.

PMID- 19155371
TI  - The COPD action plan.

PMID- 19155372
TI  - Penicillins vs trimethoprim-based regimens for acute bacterial exacerbations of
      chronic bronchitis: meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To compare the effectiveness and toxicity of semisynthetic penicillins
      (SSPs) (amoxicillin, ampicillin, pivampicillin) and trimethoprim-based regimens
      (trimethoprim, trimethoprim-sulfamethoxazole, trimethoprim-sulfadiazine) in
      treating acute bacterial exacerbations of chronic bronchitis (ABECB). DATA
      SOURCES: We searched MEDLINE, EMBASE, Current Contents, and the Cochrane Central
      Register of Controlled Trials to identify and extract data from relevant
      randomized controlled trials (RCTs). STUDY SELECTION: Only RCTs comparing
      penicillins with trimethoprim-based regimens for the treatment of patients with
      ABECB that reported data on effectiveness, toxicity, or mortality were considered
      eligible for this meta-analysis. SYNTHESIS: Out of 134 RCTs identified in the
      search, 5 RCTs involving 287 patients were included in the analysis. There were
      no differences between patients with ABECB treated with SSPs and those treated
      with trimethoprim, alone or in combination with a sulfonamide, in treatment
      success (intention-to-treat patients: n = 262, odds ratio [OR] 1.68, 95%
      confidence interval [CI] 0.91-3.09; clinically evaluable patients: n = 246, OR
      1.59, 95% CI 0.79-3.20) or number of drug-related adverse events in general (n =
      186 patients, OR 0.37, 95% CI 0.11-1.24), frequency of diarrhea or skin rashes,
      or number of withdrawals due to adverse events (n = 179 patients, OR 0.27, 95% CI
      0.07-1.03). CONCLUSION: Based on limited evidence leading to wide CIs of the
      estimated treatment effects, SSPs and trimethoprim-based regimens seem to be
      equivalent in terms of effectiveness and toxicity for ABECB.

PMID- 19155373
TI  - Changing patterns in opioid addiction: characterizing users of oxycodone and
      other opioids.
AB  - OBJECTIVE: To evaluate the clinical observation that the number of individuals
      seeking opioid detoxification from oxycodone was increasing at the Centre for
      Addiction and Mental Health (CAMH) in Toronto, Ont; and to identify the
      characteristics of individuals seeking opioid detoxification at CAMH. DESIGN:
      Retrospective analysis of patient health records. SETTING: Medical Withdrawal
      Management Service at CAMH. PARTICIPANTS: All patients admitted for opioid
      detoxification between January 2000 and December 2004. MAIN OUTCOME MEASURES:
      Number of opioid detoxification admissions each year; type, dose, and source of
      opioids; comorbid problems and symptoms. RESULTS: There were 571 opioid
      detoxification admissions during the 5-year study period. The number of
      admissions increased steadily over the 5 years; in particular, the number of
      admissions related to controlled-release oxycodone increased substantially (3.8%,
      8.3%, 20.8%, 30.6%, and 55.4% of the total opioid admissions in 2000 to 2004,
      respectively; chi(4)2= 105.5, P < .001). The rates of admissions involving heroin
      remained low and stable. Use of controlled-release oxycodone was associated with
      considerably higher doses than use of other prescription opioids was. Physician
      prescriptions were the source of the prescription opioids for a large percentage
      of patients, particularly for older patients. Prescription opioid users reported
      considerable comorbid substance use problems, pain, and psychiatric symptoms.
      CONCLUSION: This study has demonstrated a significant rise in the number of
      individuals seeking treatment at CAMH for controlled-release oxycodone addiction.
      The substantial comorbid pain, psychiatric symptoms, and other psychoactive
      substance use problems in these patients, coupled with the finding that
      prescriptions were an important source of opioids, highlight the clinical
      complexities encountered in the treatment of these individuals. Further research
      examining these complexities and the many possible pathways leading to
      prescription opioid addiction is required in order to develop effective
      prevention and treatment strategies.

PMID- 19155374
TI  - Physicians' knowledge of the epidemiology, diagnosis, and management of otitis
      media: design of a survey instrument.
AB  - OBJECTIVE: To develop a survey instrument with good internal consistency and test
      retest reliability to explore the level of knowledge among Nova Scotia family
      physicians concerning the risk factors, signs and symptoms, and treatment of
      otitis media and the use of pneumatic otoscopy. DESIGN: Prospective cohort
      design. SETTING: Fee-for-service family practices in Nova Scotia. PARTICIPANTS: A
      convenience sample of 25 family physicians. MAIN OUTCOME MEASURES: Test-retest
      reliability and internal consistency of the survey. RESULTS: The constructs
      including "signs and symptoms of otitis media with effusion" and "comprehensive
      knowledge scores" showed excellent internal consistency with Kuder-Richardson 20
      scores greater than 0.7 whereas the construct "signs and symptoms of acute otitis
      media" has a Kuder-Richardson 20 score of 0.54 after deletion of several items.
      The Cohen kappa and Spearman rho tests showed the survey has very good test
      retest reliability. CONCLUSION: The questionnaire that we developed proved to
      have very good internal consistency and test-retest reliability. We hope to use
      this questionnaire to explore the practice patterns of family physicians in
      managing otitis media disease.

PMID- 19155375
TI  - Recruiting medical students to rural practice: perspectives of medical students
      and rural recruiters.
AB  - OBJECTIVE: To explore the strategies used by rural recruitment programs and their
      perceived influence on medical students. DESIGN: Two original questionnaires
      delivered electronically, one to medical students and the other to recruiters in
      rural Ontario communities. SETTING: Ontario, Canada. PARTICIPANTS: All 525
      medical students enrolled in the Schulich School of Medicine & Dentistry at the
      University of Western Ontario in London and physician recruiters in 71 rural
      communities in Ontario were invited to participate in the study. MAIN OUTCOME
      MEASURES: The factors that influence medical students to consider rural practice,
      strategies used by recruiters, and student perceptions of the ethical
      appropriateness of both. RESULTS: The questionnaire was completed by 42.1% of
      medical students. Lifestyle considerations were an important influence for 93.1%
      of students. Themes from the qualitative analysis included the ethical
      appropriateness of financial considerations, economic forces, perceived
      disadvantages of rural practice, competition between communities, and lack of
      altruism. Responses were received from recruiters in 43.7% of communities; of
      those, 92.9% offered financial incentives to attract prospective physicians.
      CONCLUSION: Financial and lifestyle considerations are important influences on
      medical students' choice to practise in rural communities. Most medical students
      felt incentive programs offered by rural communities were ethically appropriate.

PMID- 19155376
TI  - Obstructive sleep apnea: a puzzle built in retrospect.

PMID- 19155379
TI  - Sonography of patients with hemiplegic shoulder pain after stroke: correlation
      with motor recovery stage.
AB  - OBJECTIVE: This study was performed to clarify the cause of shoulder pain using
      sonography and to evaluate the relationship between the sonographic findings and
      the motor recovery stages in stroke patients with hemiplegic shoulder pain.
      SUBJECTS AND METHODS: Between March 2005 and January 2007, 71 consecutive stroke
      patients with hemiplegic shoulder pain underwent shoulder sonography. For
      comparison, bilateral shoulder joints were evaluated in 20 of the 71 patients.
      The interpretations of the sonographic findings were based on the findings of
      previously published studies. Whether a correlation existed between the
      sonographic findings and the motor recovery stages was determined. RESULTS:
      Subacromial-subdeltoid (SA-SD) bursal effusion (n = 36) was the most common
      abnormality seen on sonography. Tendinosis of the supraspinatus tendon (n = 7),
      partial-thickness tear of the supraspinatus tendon (n = 6), and full-thickness
      tear of the supraspinatus tendon (n = 2) were also noted. Biceps tendon sheath
      effusion (n = 39) and normal findings without any biceps tendon sheath effusion
      (n = 13) were detected. Clinicians managed each patient's shoulder pain on the
      basis of the sonographic findings. No statistically significant correlation was
      found between the grade of sonographic findings and Brunnstrom stage (p = 0.183).
      A shoulder with hemiplegia had a higher number of abnormal sonographic findings
      than a noninvolved shoulder (p = 0.007). CONCLUSION: The cause of shoulder pain
      was variable and there was no correlation between the stages of motor recovery
      and the grades of sonographic findings in patients with hemiplegic shoulder pain.

PMID- 19155380
TI  - Developing a clinical decision model: MR spectroscopy to differentiate between
      recurrent tumor and radiation change in patients with new contrast-enhancing
      lesions.
AB  - OBJECTIVE: Differentiation between recurrent neoplasm and postradiation change in
      patients previously treated for primary brain tumors is often difficult based on
      imaging features alone. The purpose of this study was to develop a method using
      alterations in the ratios of standard brain metabolites-choline (Cho), creatine
      (Cr), and N-acetylaspartate (NAA)-to predict the probability of tumor recurrence
      in patients previously treated for brain tumors with new contrast-enhancing
      lesions. MATERIALS AND METHODS: Thirty-three patients who had undergone treatment
      for primary brain tumors in whom routine MRI showed new contrast-enhancing
      lesions were retrospectively studied. The final diagnosis was assigned using
      histopathology (n = 13) or imaging follow-up (n = 20; range, 2-27 months). Ratios
      of three metabolites (Cho, Cr, and NAA) were calculated, and the results were
      correlated with the final diagnosis using a Wilcoxon's rank sum analysis. A
      logistic regression model was then used to create a prediction model based on the
      most statistically significant ratio. RESULTS: Elevations of the metabolic ratios
      Cho/Cr (p < 0.001) and Cho/NAA (p < 0.001) and a decrease in the ratio NAA/Cr (p
      = 0.018) were found in patients with recurrent tumor (n = 20) versus those with
      postradiation change (n = 13). A prediction model using the Cho/NAA ratio yielded
      a sensitivity of 85%, a specificity of 69.2%, and an area under the receiver
      operating characteristic curve of 0.92. CONCLUSION: An elevated Cho/NAA ratio
      correlated with evidence of tumor recurrence and allowed creation of a prediction
      rule to aid in lesion classification. The results suggest that MR spectroscopy is
      a useful tool in assigning patients with nonspecific enhancing lesions to either
      invasive biopsy or conservative management.

PMID- 19155381
TI  - Bilateral thalamic lesions.
AB  - OBJECTIVE: The purpose of this study was to present the neuroimaging findings and
      differential diagnosis of bilateral thalamic lesions. CONCLUSION: The limited
      differential diagnosis of bilateral thalamic lesions can be further narrowed with
      knowledge of the specific imaging characteristics of the lesions in combination
      with the patient history.

PMID- 19155382
TI  - Carotid artery abnormalities and leukoaraiosis in elderly patients: evaluation
      with MDCT.
AB  - OBJECTIVE: Several studies have shown that leukoaraiosis is a clinically relevant
      condition. Patients with leukoaraiosis have a negative prognosis in terms of
      death, stroke, and myocardial infarction. The aim of this study was to evaluate
      whether the presence and severity of leukoaraiosis correlate with degree of
      carotid stenosis and the presence of specific types of plaque (fatty, mixed,
      calcified) in a group of elderly patients with clinical indications for MDCT.
      MATERIALS AND METHODS: From January 2004 to March 2007, 147 consecutively
      registered patients 65 years and older underwent MDCT. All patients enrolled in
      the study cohort were assessed for the presence and severity of leukoaraiosis.
      Degree of carotid artery stenosis according to the North American Symptomatic
      Carotid Endarterectomy Trial criteria and type of plaque were evaluated.
      Statistical analysis was performed to determine whether an independent
      interaction existed among the presence of leukoaraiosis, severity of
      leukoaraiosis, and degree of carotid artery stenosis associated with plaque type.
      RESULTS: A correlation was observed between the presence of leukoaraiosis and
      degree of carotid stenosis (Pearson correlation, 0.23; p < 0.001). A
      statistically significant correlation between advanced patient age and presence
      of leukoaraiosis (Pearson correlation, 0.32; p < 0.0001) and severity of
      leukoaraiosis (Pearson correlation, 0.55; p < 0.0001) was recorded. The data
      obtained showed a trend toward increased risk of development of leukoaraiosis (p
      = 0.08) in carotid arteries with fatty plaques. CONCLUSION: The results of this
      study showed a statistically significant correlation between the presence and
      severity of leukoaraiosis and degree of carotid stenosis. A trend toward
      increased risk of development of leukoaraiosis in carotids with fatty plaques
      also was observed. The data confirmed that the development of leukoaraiosis is
      strongly correlated with age.

PMID- 19155383
TI  - PACStacker: an enhancement of the scientific and educational capabilities of
      PowerPoint.
AB  - OBJECTIVE: Our objective was to develop a way to enhance scientific and
      educational PowerPoint presentations containing stack-based, multiple-image
      techniques such as CT and MRI. CONCLUSION: We developed a PowerPoint add-in that
      facilitates the creation of stackable image sets in a simple and intuitive
      manner, permitting real-time scrolling, editing, and manipulation of imbedded
      image stacks. Contrast and brightness adjustments, cropping, and linking are
      supported. Once created, the PowerPoint presentation can be viewed without
      hardware or venue limitations on any computer, without reinstallation of the add
      in.

PMID- 19155384
TI  - Penumbra imaging as a prognostic indicator for acute myocardial infarction using
      MDCT.

PMID- 19155385
TI  - Role of MDCT in the evaluation of prosthetic heart valves.

PMID- 19155386
TI  - Achilles wiiitis.

PMID- 19155387
TI  - Nonionic iodinated contrast media reactions.

PMID- 19155388
TI  - Mechanical devices for arterial occlusion and therapeutic vascular occlusion
      utilizing steel coil technique: clinical applications.

PMID- 19155389
TI  - Declining utilization of screening mammography: the gathering storm.

PMID- 19155391
TI  - Malpractice and breast cancer: perceptions versus reality.

PMID- 19155390
TI  - Predictors of radiologists' perceived risk of malpractice lawsuits in breast
      imaging.
AB  - OBJECTIVE: The shortage of radiologists in breast imaging may be related to
      heightened malpractice lawsuit concerns. Our objective was to examine
      radiologists' reported experiences and perceptions of future lawsuit risk and
      explore personal and professional factors that may be associated with elevated
      perceptions of risk. MATERIALS AND METHODS: Radiologists who routinely interpret
      mammography examinations in diverse regions of the United States (Washington,
      Colorado, and New Hampshire) completed a mailed survey in 2002 and 2006,
      including questions on demographics, practice characteristics, and medicolegal
      experience and perceptions as well as a validated scale measuring reactions to
      uncertainty in clinical situations. A survey assessing the radiologists' work
      facilities was also completed in 2002. RESULTS: Participation by eligible
      radiologists was 77% (139 of 181) in 2002 and 71% (84 of 118) in 2006. The
      percentage of radiologists reporting malpractice claims related to mammography in
      the previous 5 years was 8% on the 2002 survey and 10% on the 2006 survey.
      Radiologists' mean estimate of the probability of being sued for malpractice in
      the next 5 years (41% in 2002 and 35% in 2006) was markedly higher than the
      actual reported risk. Radiologists' age, sex, clinical experience, and workload
      were not associated with a higher perceived risk of being sued. Radiologists who
      reported higher perceived risk of lawsuits were more likely to have experienced a
      prior malpractice claim, to report knowing colleagues with prior lawsuits, and to
      score higher on a scale measuring anxiety caused by uncertainty in clinical
      situations. Radiologists working at facilities that did not use double reading
      reported higher perceived risk, but the difference was not statistically
      significant. CONCLUSION: Radiologists working in breast imaging substantially
      overestimate their risk of a future malpractice lawsuit. Radiologists with higher
      risk perceptions show more negative reactions to uncertainty in a clinical
      setting. Understanding that their actual risk of malpractice lawsuits may be
      substantially lower than anticipated may help reduce radiologists' fears and
      alleviate the manpower shortage in mammography. Programs to address the shortage
      of breast imagers could be targeted toward radiologists with heightened
      malpractice lawsuit concerns.

PMID- 19155392
TI  - Detection of breast cancer with full-field digital mammography and computer-aided
      detection.
AB  - OBJECTIVE: The purpose of this study was to evaluate computer-aided detection
      (CAD) performance with full-field digital mammography (FFDM). MATERIALS AND
      METHODS: CAD (Second Look, version 7.2) was used to evaluate 123 cases of breast
      cancer detected with FFDM (Senographe DS). Retrospectively, CAD sensitivity was
      assessed using breast density, mammographic presentation, histopathology results,
      and lesion size. To determine the case-based false-positive rate, patients with
      four standard views per case were included in the study group. Eighteen
      unilateral mammography examinations with nonstandard views were excluded,
      resulting in a sample of 105 bilateral cases. RESULTS: CAD detected 115 (94%) of
      123 cancer cases: six of six (100%) in fatty breasts, 63 of 66 (95%) in breasts
      containing scattered fibroglandular densities, 43 of 46 (93%) in heterogeneously
      dense breasts, and three of five (60%) in extremely dense breasts. CAD detected
      93% (41/44) of cancers manifesting as calcifications, 92% (57/62) as masses, and
      100% (17/17) as mixed masses and calcifications. CAD detected 94% of the invasive
      ductal carcinomas (n = 63), 100% of the invasive lobular carcinomas (n = 7), 91%
      of the other invasive carcinomas (n = 11), and 93% of the ductal carcinomas in
      situ (n = 42). CAD sensitivity for cancers 1-10 mm (n = 55) was 89%; 11-20 mm (n
      = 37), 97%; 21-30 mm (n = 16), 100%; and larger than 30 mm (n = 15), 93%. The CAD
      false-positive rate was 2.3 marks per four-image case. CONCLUSION: CAD with FFDM
      showed a high sensitivity in identifying cancers manifesting as calcifications
      and masses. Sensitivity was maintained in cancers with lower mammographic
      sensitivity, including invasive lobular carcinomas and small neoplasms (1-20 mm).
      CAD with FFDM should be effective in assisting radiologists with earlier
      detection of breast cancer. Future studies are needed to assess CAD accuracy in
      larger populations.

PMID- 19155393
TI  - False-negative diagnoses at stereotactic vacuum-assisted needle breast biopsy:
      long-term follow-up of 1,280 lesions and review of the literature.
AB  - OBJECTIVE: The purpose of this study was to determine retrospectively the
      frequency and causes of false-negative diagnoses of lesions evaluated with
      percutaneous stereotactic biopsy performed with vacuum-assisted probes with the
      patient prone on a biopsy table. MATERIALS AND METHODS: The records of 1,152
      women (median age, 55 years; range, 31-94 years) with 1,280 lesions consecutively
      biopsied with 14-gauge (n = 159) or 11-gauge (n = 1,121) vacuum probes were
      reviewed retrospectively. The histologic diagnoses were malignant (n = 489), high
      risk (n = 117), and benign (n = 674) lesions. Benign lesions were evaluated with
      repeated biopsy (n = 46) or mammographic follow-up for 24 months or longer (n =
      506) or less than 24 months (n = 57). In 65 cases (10% of all benign lesions),
      follow-up was not performed. Fisher's exact tests were used to correlate patient,
      mammographic, and biopsy variables with false-negative diagnoses. RESULTS: Of 508
      lesions with a final diagnosis of malignancy, the initial needle biopsy diagnosis
      was malignant (n = 489), high-risk (n = 14), or benign (n = 5) lesion. The five
      false-negative diagnoses were related to gauge of the biopsy probe and specimen
      radiographic findings regarding calcifications but were not related to lesion
      type. False-negative diagnoses were made in 4.4% (three of 68) of cases in which
      14-gauge vacuum biopsy was performed and in 0.45% (two of 440) of cases in which
      11-gauge vacuum biopsy was performed (p = 0.019). False-negative diagnoses were
      made in 25% (one of four) of cases in which specimen radiographs showed no
      calcifications and 0.67% (two of 300) of cases in which they did show
      calcifications (p = 0.0390). False-negative diagnoses were made in 1.2% (three of
      248) of cases of calcification lesions and 0.8% (two of 260) of cases of mass
      lesions (p = 0.679). CONCLUSION: False-negative findings at stereotactic biopsy
      were least common with 11-gauge probes and were similar in frequency for
      calcifications and masses.

PMID- 19155394
TI  - Mammography use from 2000 to 2006: state-level trends with corresponding breast
      cancer incidence rates.
AB  - OBJECTIVE: Although breast cancer incidence and mortality rates have declined, a
      significant number of women are affected by this disease each year. Mammography
      is currently the most effective way to detect breast cancer at an early stage
      when it is most treatable, but there have been reports of decreasing or stagnant
      mammography use in the United States. For this study, we investigated the trend
      in mammography use for each state in comparison with the corresponding breast
      cancer incidence trend. MATERIALS AND METHODS: We used data from the Behavioral
      Risk Factor Surveillance System for 2000, 2002, 2004, and 2006 to assess the
      percentage of women >or= 40 years old who reported undergoing mammography within
      the past 2 years and data from the National Program of Cancer Registries and the
      Surveillance, Epidemiology, and End Results Program to assess breast cancer
      incidence rates from 2000 through 2004, the latest year for which data were
      available at the time of the study. RESULTS: The majority of states had a
      decreasing tendency in mammography use from 2000 to 2006. Only one state had a
      statistically significant increase in reported mammography use, whereas two
      states had significant decreases. There was a correlation between breast cancer
      incidence rates and mammography use by states (r = 0.6), but no correlation
      between the time trends in breast cancer incidence rates and mammography use was
      observed. CONCLUSION: There was little statistically significant change in self
      reported mammography use from 2000 to 2006. Continued monitoring of breast cancer
      screening practices and breast cancer incidence trends is important for targeting
      at-risk populations with effective interventions to improve breast cancer
      prevention and early detection.

PMID- 19155395
TI  - Radiologists' performance and their enjoyment of interpreting screening
      mammograms.
AB  - OBJECTIVE: One might speculate that radiologists who enjoy mammography may
      exhibit better performance than radiologists who do not. MATERIALS AND METHODS:
      One hundred thirty-one radiologists at three Breast Cancer Surveillance
      Consortium (BCSC) registries completed a survey about their characteristics,
      clinical practices, and attitudes related to screening mammography. Survey
      results were linked with BCSC performance data for 662,084 screening and 33,977
      diagnostic mammograms. Using logistic regression, we modeled the odds of an
      abnormal interpretation, cancer detection, sensitivity, and specificity among
      radiologists who reported they enjoy interpreting screening mammograms compared
      with those who do not. RESULTS: Overall, 44.3% of radiologists reported not
      enjoying interpreting screening mammograms. Radiologists who reported enjoying
      interpreting screening mammograms were more likely to be women, spend at least
      20% of their time in breast imaging, have a primary academic affiliation, read
      more than 2,000 mammograms per year, and be salaried. Enjoyment was not
      associated with screening mammography performance. Among diagnostic mammograms,
      there was a significant increase in sensitivity among radiologists who reported
      enjoyment (85.2%) compared with those who did not (78.2%). In models adjusting
      for radiologist characteristics, similar trends were found; however, no
      statistically significant associations remained. CONCLUSION: Almost one half of
      radiologists actively interpreting mammograms do not enjoy that part of their
      job. Once we adjusted for radiologist and patient characteristics, we found that
      reported enjoyment was not related to performance in our study, although
      suggestive trends were noted.

PMID- 19155396
TI  - Workforce shortages in breast imaging: impact on mammography utilization.
AB  - OBJECTIVE: The objective of this study was to develop reliable forecasts of the
      future supply of radiologists and radiologic technologists practicing mammography
      under different assumptions about future introduction of new practitioners. In
      addition, this article includes basic mammography workforce statistics to provide
      a context for the forecasts. MATERIALS AND METHODS: The forecasts were developed
      using an age cohort flow model based on data provided by the American College of
      Radiology (ACR) on the numbers and age distribution of radiologists and on data
      provided by the American Society of Radiologic Technologists (ASRT) on radiologic
      technologists providing mammography services. RESULTS: The forecasts show that
      the current rates of production of new mammography professionals will result in
      dramatic reductions in mammography professionals per woman age 40 years old and
      older over the next 15-20 years. CONCLUSION: Unless the number of new mammography
      professionals entering practice every year increases beyond the current levels,
      there will be a growing gap between the supply of and demand for mammography
      professionals over the next two decades.

PMID- 19155397
TI  - Invasive lobular carcinoma: detection with mammography, sonography, MRI, and
      breast-specific gamma imaging.
AB  - OBJECTIVE: The objective of our study was to compare the sensitivity of
      mammography, sonography, MRI, and breast-specific gamma imaging (BSGI) in the
      detection of invasive lobular carcinoma. MATERIALS AND METHODS: This is a
      retrospective multicenter study of women with biopsy-proven invasive lobular
      carcinoma. All patients had undergone mammography and BSGI, and the imaging
      findings were classified as positive or negative for invasive lobular carcinoma
      by experienced breast imagers. The results of MRI and sonography, if either was
      performed, were included. Final surgical pathology results were used as the
      reference standard and the lesion sensitivities of BSGI, mammography, sonography,
      and MRI were then statistically compared using CIs. RESULTS: Twenty-six women
      ranging in age from 46 to 82 years (mean age, 62.8 years) with a total of 28
      biopsy-proven invasive lobular carcinomas were included in the study group.
      Mammograms were negative in six of 28 (21%), yielding a sensitivity of 79%. In
      the 25 patients who underwent sonography, 17 had focal hypoechoic areas, yielding
      a sensitivity of 68%. In the 12 patients who underwent MRI, the sensitivity was
      83%. BSGI had a sensitivity of 93%. There was no statistically significant
      difference in the sensitivity of BSGI, MRI, sonography, or mammography, although
      there was a nonsignificant trend toward improved detection with BSGI. CONCLUSION:
      BSGI has the highest sensitivity for the detection of invasive lobular carcinoma
      with a sensitivity of 93%, whereas mammography, sonography, and MRI showed
      sensitivities of 79%, 68%, and 83%, respectively. BSGI is an effective technique
      that should be used to evaluate patients with suspected cancer and has a
      promising role in the diagnosis of invasive lobular carcinoma.

PMID- 19155398
TI  - Image registration for detection and quantification of change on digital
      tomosynthesis mammographic volumes.
AB  - OBJECTIVE: The purpose of this study was to achieve 3D registration of digital
      tomosynthesis mammographic volumes using mutual information. CONCLUSION:
      Registration of digital breast tomosynthesis mammographic volumes was achieved
      with an average error of 1.8 +/- 1.4 mm.

PMID- 19155399
TI  - Declining screening mammography rates: a multigenerational loss of opportunity?

PMID- 19155400
TI  - Tailored supplemental screening for breast cancer: what now and what next?
AB  - OBJECTIVE: This article reviews breast cancer risk assessment and the rationale
      for current screening guidelines, including when to consider using supplemental
      screening with MRI or sonography in addition to mammography, and discusses other
      emerging technologies. Radiologists can help identify women who may benefit from
      supplemental screening and can help to recommend when and which techniques to
      perform for this additional screening. CONCLUSION: Mammography remains the
      mainstay of breast cancer screening. Mammography should be performed as digital
      imaging when possible in women with dense breasts. In women at high risk,
      particularly if they also have dense breasts, annual MRI is recommended, although
      further validation of outcomes is needed. In intermediate-risk women with dense
      breasts, especially those with other risk factors, and in high-risk women with
      dense breasts who are unable to tolerate MRI, supplemental sonography screening
      is an option at facilities with availability of qualified personnel. Developing
      technologies are not appropriate for screening at this time, although further
      study is encouraged.

PMID- 19155401
TI  - Decreased mammography utilization in the United States: why and how can we
      reverse the trend?
AB  - OBJECTIVE: Recent studies have demonstrated that mammography utilization in the
      United States has decreased. The purpose of this article is to review some of the
      causes and possible interventions to reverse the trend of decreased mammography
      utilization. CONCLUSION: Explanations for decreased mammography utilization
      include decreased availability of mammography sites, stress associated with
      mammography interpretation, the litigious environment of breast cancer diagnosis,
      and inappropriately low reimbursement. Possible approaches to rectifying these
      barriers are discussed.

PMID- 19155402
TI  - Breast imaging fellowships in the United States: who, what, and where?
AB  - OBJECTIVE: The purpose of this study was to determine the characteristics of
      fellowship programs offering breast imaging training and their success in filling
      positions. CONCLUSION: A comprehensive list of fellowship training opportunities
      in breast imaging may help potential applicants identify relevant programs.

PMID- 19155403
TI  - CT diagnosis of acute mesenteric ischemia from various causes.
AB  - OBJECTIVE: Acute mesenteric ischemia can be caused by various conditions such as
      arterial occlusion, venous occlusion, strangulating obstruction, and
      hypoperfusion associated with nonocclusive vascular disease, and the CT findings
      vary widely depending on the cause and underlying pathophysiology. The aim of
      this article is to review the CT appearances of acute mesenteric ischemia in
      various conditions. CONCLUSION: Recognition of characteristic CT appearances and
      the variations associated with each cause may help in the accurate interpretation
      of CT in the diagnosis of mesenteric ischemia.

PMID- 19155404
TI  - Mural attenuation in normal small bowel and active inflammatory Crohn's disease
      on CT enterography: location, absolute attenuation, relative attenuation, and the
      effect of wall thickness.
AB  - OBJECTIVE: The purpose of our study was to measure relative and absolute wall
      attenuations and wall thickness in normal small bowel on contrast-enhanced CT
      enterography and to study the efficacy of relative attenuation, absolute
      attenuation, and wall thickness in distinguishing normal from active inflammatory
      Crohn's disease of the terminal ileum. MATERIALS AND METHODS: Using a case
      control study design, we reviewed 630 CT enterography examinations, of which 191
      were normal and 36 had active inflammatory Crohn's disease in the terminal ileum.
      In healthy individuals, wall thickness and attenuation in distended and collapsed
      loops were measured in the duodenum and four abdominal quadrants. Wall thickness
      and attenuation were also measured in the terminal ileum. All measurements of
      intraarterial attenuation were taken at the same slice level. In the examinations
      of patients with Crohn's disease, only terminal ileum wall thickness and
      attenuation as well as arterial attenuation at the same slice level were
      measured. Normal segments were compared with a linear model. Terminal ileum data
      were fit to a multivariate logistic regression model. RESULTS: Relative
      attenuation and absolute attenuation in the normal distended and collapsed
      duodenum and left upper quadrant were significantly greater than in all other
      segments (p < 0.001 and < 0.048 for relative attenuation and p < 0.001 and <
      0.032 for absolute attenuation, respectively). Relative attenuation and wall
      thickness models and absolute attenuation and wall thickness models discriminated
      normal from active terminal ileum Crohn's disease significantly better than the
      same measurements without wall thickness (p = 0.017 and 0.001, respectively).
      When the bowel wall is > 3 mm, a relative attenuation cutoff of 0.5 is 89%
      sensitive and 81% specific. CONCLUSION: In normal small bowel, when wall
      measurement is taken into account, the duodenum and jejunum have a greater
      relative attenuation and absolute attenuation than other segments. Relative
      attenuation and absolute attenuation with wall thickness models discriminate
      normal from active terminal ileum Crohn's disease better than the same
      measurements without wall thickness.

PMID- 19155405
TI  - Contrast-enhanced sonography of nonfunctioning pancreatic neuroendocrine tumors.
AB  - OBJECTIVE: Diagnosis of malignancy and prognostic assessment continue to be
      problems in the management of nonfunctioning pancreatic endocrine tumors.
      Histologic examination is the reference standard. The aim of our study was to
      compare B-mode and contrast-enhanced sonographic findings regarding
      nonfunctioning pancreatic endocrine tumors. Signs of malignancy, such as Ki67
      index and presence of hepatic metastasis, were considered. MATERIALS AND METHODS:
      We retrospectively reviewed the cases of 38 consecutively registered patients
      with nonfunctioning pancreatic endocrine tumors evaluated with B-mode and
      contrast-enhanced sonography and resected. At contrast-enhanced sonography all
      lesions were divided into hypovascular lesions and isovascular or hypervascular
      lesions. On the basis of homogeneity of enhancement, lesions were classified as
      homogeneous and inhomogeneous. During the late phase of contrast enhancement, all
      solid focal hypoechoic liver lesions detected at contrast-enhanced sonography
      were considered hepatic metastatic lesions. Among pathologic data, grading,
      mitotic index, and Ki67 index were evaluated. Spearman's test was used to compare
      contrast-enhanced sonographic enhancement pattern with pathologic grade. RESULTS:
      In the arterial phase, 24 of 38 nonfunctioning pancreatic endocrine tumors
      (63.1%) were hypervascular, seven (18.4%) were isovascular, and seven (18.4%)
      were hypovascular. Positive correlation was found between contrast-enhanced
      sonographic findings and Ki67 index (r(s) = 0.62; p < 0.0001). The difference
      between contrast-enhanced and B-mode sonography in the diagnosis of
      nonfunctioning pancreatic endocrine tumors was statistically significant (p <
      0.05). Use of contrast-enhanced sonography increased diagnostic confidence in the
      detection of hepatic metastasis. The areas under the receiver operating
      characteristic curves were 0.916 for B-mode sonography and 1.000 for contrast
      enhanced sonography (p < 0.05). There was moderate positive correlation between
      contrast-enhanced sonographic enhancement pattern and the presence of hepatic
      metastasis at diagnosis (r(s) = 0.46; p = 0.004) and between Ki67 index and the
      presence of hepatic metastasis (r(s) = 0.48; p = 0.0022). CONCLUSION: The
      contrast-enhanced sonographic enhancement pattern of nonfunctioning pancreatic
      endocrine tumors has a positive correlation with Ki67 index, which is considered
      the most reliable independent predictor of the presence of malignancy.

PMID- 19155406
TI  - Autoimmune pancreatitis: pancreatic and extrapancreatic imaging findings.
AB  - OBJECTIVE: The purpose of this article is to discuss the systemic nature of
      autoimmune pancreatitis and its various pancreatic and extrapancreatic imaging
      findings. CONCLUSION: Autoimmune pancreatitis is a systemic disease with a wide
      range of pancreatic and extrapancreatic imaging findings. These findings can
      mimic those of other diseases in the pancreas or other organs and therefore are
      commonly misdiagnosed and mistreated. It is important for radiologists to
      understand both the pancreatic and extrapancreatic imaging findings of autoimmune
      pancreatitis to make accurate and timely diagnoses.

PMID- 19155407
TI  - Angiomyolipoma with minimal fat on MDCT: can counts of negative-attenuation
      pixels aid diagnosis?
AB  - OBJECTIVE: The purpose of this study was to determine whether counts of pixels
      with subzero attenuation on CT scans can aid in the diagnosis of renal
      angiomyolipoma with minimal fat. MATERIALS AND METHODS: Of 33 angiomyolipomas
      identified among 719 renal masses resected from 702 patients over 4 years, 15
      masses in 15 patients were prospectively diagnosed on the basis of the presence
      of fat at MDCT. The 18 patients with minimal-fat angiomyolipoma and a matched
      (age, sex, tumor size) cohort of patients with renal cell carcinoma were included
      in this study. Three radiologists independently counted the number of pixels with
      attenuation less than -10, -20, and -30 HU. Receiver operating characteristic
      analysis of the number of pixels at each cutoff was used to calculate
      sensitivity, specificity, and positive predictive value with the following
      criteria: 1, more than 10 pixels less than -20 HU; 2, more than 20 pixels less
      than -20 HU; 3, more than 5 pixels less than -30 HU. RESULTS: Using criterion 1,
      reader A identified six angiomyolipomas; reader B, five; and reader C, two. The
      combined sensitivity was 24%; specificity, 98%; and positive predictive value,
      69%. Using criterion 2, reader A identified three angiomyolipomas; reader B,
      four; and reader C, two. The combined sensitivity was 17%; specificity, 100%; and
      positive predictive value, 100%. Using criterion 3, reader A identified four
      angiomyolipomas; reader B, four; and reader C, two. The combined sensitivity was
      18%; specificity, 100%; and positive predictive value, 100%. CONCLUSION: CT
      findings of more than 20 pixels with attenuation less than -20 HU and more than 5
      pixels with attenuation less than -30 HU have a positive predictive value of 100%
      in detection of angiomyolipoma, but most angiomyolipomas with minimal fat cannot
      be reliably identified on the basis of an absolute pixel count.

PMID- 19155408
TI  - Interobserver variability of transrectal ultrasound for prostate volume
      measurement according to volume and observer experience.
AB  - OBJECTIVE: The purpose of our study was to evaluate the interobserver variability
      of transrectal ultrasound for prostate volume measurement according to the
      prostate volume and the level of observer experience. SUBJECTS AND METHODS:
      Endorectal sonography was performed independently by two experienced observers in
      101 patients and by one experienced and one less experienced observer in 110
      patients; the prostate volume was then measured using the prolate ellipsoid
      formula. The volume difference between observers was analyzed according to the
      mean measured prostate volume determined by the observers and according to the
      level of observer experience. RESULTS: The volume difference was greater in
      prostates with a mean measured volume >or= 30 mL than in prostates with a mean
      measured volume < 30 mL (6.00 vs 1.51 mL in the experienced observers and 6.84 vs
      3.99 mL in the experienced and less experienced observers) (p < 0.05). The
      frequency of volume differences > 5 mL was greater in prostates with a mean
      measured volume >or= 30 mL than in prostates with a mean measured volume < 30 mL
      (between the experienced observers, 18% vs 1%; between the experienced and less
      experienced observers, 54% vs 25%) (p < 0.01 in both comparisons). The volume
      difference was greater between the experienced and less experienced observers
      (5.00 mL) than between the experienced observers (2.96 mL) (p = 0.01). The
      frequency of volume difference > 5 mL was greater between the experienced and
      less experienced observers (35%) than between the experienced observers (7%) (p <
      0.01). CONCLUSION: Prostate volume measurement by transrectal ultrasound may vary
      when patients have large prostates or observers have varying levels of
      experience.

PMID- 19155409
TI  - Characterization of adrenal pheochromocytoma using respiratory-triggered proton
      MR spectroscopy: initial experience.
AB  - OBJECTIVE: The aim of our study was to evaluate the feasibility of respiratory
      triggered proton single-voxel MR spectroscopy for the diagnosis of adrenal
      pheochromocytoma and to determine whether certain spectral resonances detected on
      single-voxel MR spectroscopy are specific for adrenal pheochromocytomas compared
      with adrenal adenomas. CONCLUSION: Adrenal pheochromocytomas have a unique MR
      spectral signature, showing 6.8 ppm resonance that is not seen in adenomas. This
      unique spectral signature may be attributed to the presence of catecholamines and
      catecholamine metabolites that are abundant in pheochromocytomas.

PMID- 19155410
TI  - Use of IV epinephrine for treatment of patients with contrast reactions: lessons
      learned from a 5-year experience.
AB  - OBJECTIVE: The purpose of this study was to review the use of epinephrine in the
      management of contrast reactions and to evaluate the appropriateness of the
      clinical indication, side effects and complications, and outcome. CONCLUSION:
      Severe contrast reactions necessitating treatment with epinephrine are rare. The
      most common clinical indication is laryngeal edema. Cardiovascular side effects
      of epinephrine occur, but most are self-limited.

PMID- 19155411
TI  - Multitechnique evaluation of renal hydatid disease.
AB  - OBJECTIVE: Hydatid involvement of the kidney accounts for only 2-4% of all cases
      of hydatid disease. The purpose of this article is to review the imaging features
      of hydatid disease of the kidney and thus show the role of radiography, excretory
      urography, sonography, CT, and MRI in the diagnosis of hydatidosis. CONCLUSION:
      The radiologist should be familiar with the imaging findings of hydatid disease
      because early diagnosis is important for more appropriate treatment.

PMID- 19155412
TI  - Distal attachment of the brachialis muscle: anatomic and MRI study in cadavers.
AB  - OBJECTIVE: The purpose of this study was to use MRI and anatomic correlation in
      cadavers to delineate the anatomic features of the distal attachment of the
      brachialis muscle. MATERIALS AND METHODS: MRI was performed on 13 cadaveric
      elbows. The MRI findings were compared with those in anatomic sections and
      histologic preparations. The brachialis muscle of one cadaver was dissected.
      RESULTS: The dissected brachialis muscle had two heads, superficial and deep. The
      attachment of the superficial head to the ulnar tuberosity was farther distal
      than that of the deep head. The attachments of all aspects of the muscle included
      a tendinous layer rather than purely muscular structures. Histologic analysis
      showed no direct communication between the brachialis and biceps brachii tendons
      or between the brachialis tendon and joint capsule. CONCLUSION: Familiarity with
      the anatomic features of the distal brachialis muscle and tendon is essential for
      accurate assessment of these structures.

PMID- 19155413
TI  - Comparison of indirect isotropic MR arthrography and conventional MR arthrography
      of labral lesions and rotator cuff tears: a prospective study.
AB  - OBJECTIVE: The purpose of our study was to prospectively compare the diagnostic
      accuracy of 3D isotropic indirect MR arthrography with conventional sequences of
      indirect MR arthrography for the diagnosis of labral and rotator cuff lesions on
      a 3-T MR unit. SUBJECTS AND METHODS: Thirty-six consecutive patients who were
      scheduled for shoulder arthroscopic surgery at our institution underwent indirect
      MR arthrography. Both conventional sequences and an additional 3D isotropic
      sequence were obtained 1 day before arthroscopic surgery. Two musculoskeletal
      radiologists prospectively evaluated the images in consensus for the presence of
      superior and anterior labral lesions and subscapularis and supraspinatus
      infraspinatus tendon tears using the conventional sequences and the 3D isotropic
      sequence. We analyzed the statistical difference between the sensitivities and
      specificities of both methods using arthroscopic findings as the reference
      standard. RESULTS: Surgical findings confirmed the presence of 23 superior labral
      lesions, eight anterior labral lesions, 21 subscapularis tears, and 24
      supraspinatus-infraspinatus tears. The sensitivity and specificity of the
      conventional sequences were 74% and 54% for superior labral lesions, 88% and 96%
      for anterior labral lesions, 67% and 85% for subscapularis tendon tears, and 96%
      and 75% for supraspinatus-infraspinatus tendon tears. The sensitivity and
      specificity of the 3D isotropic sequence were 70% and 85% for superior labral
      lesions, 100% and 100% for anterior labral lesions, 67% and 85% for subscapularis
      tendon tears, and 96% and 67% for supraspinatus-infraspinatus tendon tears. No
      statistically significant difference was seen in sensitivities and specificities
      for both methods. CONCLUSION: Three-dimensional isotropic MR arthrography
      sequences with multiplanar reconstruction can provide a similar capability for
      the diagnosis of labral and rotator cuff lesions as conventional MR arthrography
      sequences but in a shorter imaging time.

PMID- 19155414
TI  - MR diagnosis of posterior root tears of the lateral meniscus using arthroscopy as
      the reference standard.
AB  - OBJECTIVE: The purpose of our study was to determine whether tears of the
      posterior root of the lateral meniscus can be diagnosed using standard MR
      criteria of a meniscal tear in the presence or absence of an anterior cruciate
      ligament (ACL) tear. MATERIALS AND METHODS: From a series of 559 knee MR
      examinations with arthroscopic correlation, we selected all 16 proven tears
      isolated to the posterior root of the lateral meniscus for retrospective blinded
      review, along with 45 cases of arthroscopically intact lateral meniscal posterior
      roots. The reviewers categorized whether there was a torn, possibly torn, or
      intact root based on three specific coronal and three specific sagittal image
      locations. RESULTS: When all possibly torn roots were considered as torn, the
      sensitivity and specificity for diagnosis of a root tear were 93% and 89%,
      respectively. The observers' overall diagnosis of a tear based on all images gave
      a higher combined sensitivity and specificity than if the diagnosis of a tear had
      been based on one or any combination of the three coronal and three sagittal
      locations. Root tears were significantly more common in the presence of an ACL
      tear (p < 0.0001), but the presence or absence of an ACL tear did not change MR
      diagnostic accuracy. CONCLUSION: The standard MR criteria of meniscal distortion
      and signal to the surface can be used to diagnose lateral meniscal root tears.
      The presence or absence of an ACL tear did not change diagnostic accuracy.

PMID- 19155415
TI  - Sonography of the normal ankle: a target approach using skeletal reference
      points.
AB  - OBJECTIVE: Sonographic examination of the ankle depends on exact knowledge of the
      specific probe positions to acquire the best images. CONCLUSION: In this article,
      we discuss these positions and illustrate them with drawings, anatomic slices or
      dissection, and sonograms. Positions studied include those for best imaging of
      the anterior tibiotalar joint, anterior tibiofibular ligament, anterior
      talofibular ligament, calcaneofibular ligament, peroneal tendons, Achilles
      tendon, flexor hallucis longus, posterior deltoid ligament, anterior deltoid
      ligament, and posterior medial tendons.

PMID- 19155416
TI  - Correlation of arthrodesis stability with degree of joint fusion on MDCT.
AB  - OBJECTIVE: The purpose of our study was to correlate clinically determined joint
      stability with the degree of bone fusion in the ankle or subtalar joint on MDCT
      examinations after arthrodesis. MATERIALS AND METHODS: We performed a
      retrospective review of 42 consecutive MDCT examinations from 29 patients. All
      patients had previously undergone arthrodesis of their ankle or subtalar joints
      and had persistent or recurrent hindfoot or ankle pain. Two musculoskeletal
      radiologists examined in consensus sagittal 2-mm-thick reformatted slices,
      measuring on each image the length of the joint surface and the length of the
      fused portion of the joint space. The sum of the lengths of the fused segments on
      all slices was then divided by the sum of the lengths of the joint surfaces to
      calculate the fusion ratio. For the standard of reference, the medical records
      were reviewed and operative reports, diagnostic injections, and physical
      examinations were used to classify the joints as stable or unstable. RESULTS:
      Twelve clinically unstable joints had fusion ratios of 0-32.8%, whereas 30
      clinically stable joints had fusion ratios of 33.2-100%. Using receiver operating
      characteristic analysis, we selected the cutoff level that maximized Youden's
      index (the sum of sensitivity and specificity). Using a 33% fusion ratio as the
      lower limit cutoff for joint stability, the sensitivity was 100%; specificity,
      100%; and accuracy, 100%. CONCLUSION: After arthrodesis of the ankle or subtalar
      joint, MDCT scans can be used to determine whether that joint is likely to be
      stable if > 33% of the joint has visible bone fusion on sagittal MDCT images.

PMID- 19155417
TI  - Neuroimaging findings in acute Wernicke's encephalopathy: review of the
      literature.
AB  - OBJECTIVE: Wernicke's encephalopathy is an acute neurological syndrome resulting
      from thiamine (vitamin B1) deficiency. Early recognition is important because
      timely thiamine supplementation can reverse the clinical features of the disease.
      The aim of this article is to provide an update on the typical and atypical
      neuroimaging findings of the acute phase of the disease. CONCLUSION: Wernicke's
      encephalopathy is characterized by a quite distinct pattern of MR alterations,
      which include symmetrical alterations in the thalami, mamillary bodies, tectal
      plate, and periaqueductal area, but atypical alterations may also been seen. A
      thorough knowledge of the neuroimaging findings of Wernicke's encephalopathy will
      assist in arriving at an early diagnosis, thus reducing the morbidity and
      mortality associated with this disease.

PMID- 19155418
TI  - Comparison of ablation zone between 915- and 2,450-MHz cooled-shaft microwave
      antenna: results in in vivo porcine livers.
AB  - OBJECTIVE: The objective of our study was to compare the ablation zones of two
      cooled-shaft microwave antennae-one operating at 915 MHz and one operating at
      2,450 MHz-in in vivo porcine livers. CONCLUSION: The 915-MHz cooled-shaft
      microwave antenna can lead to deeper penetration of liver tissue and can yield a
      significantly larger ablation zone than the 2,450-MHz cooled-shaft antenna in in
      vivo porcine livers. In light of the result, 915-MHz cooled-shaft microwaves may
      be more effective for tumor ablation, especially for large tumors.

PMID- 19155419
TI  - MDCT angiography of thoracic aorta endovascular stent-grafts: pearls and
      pitfalls.
AB  - OBJECTIVE: The objective of our study was to review expected findings and
      complications after thoracic endovascular aortic repair on CT angiography (CTA).
      CONCLUSION: Luminal and extraluminal changes to the thoracic aorta occur after
      endovascular stent-grafting. The radiologist can facilitate appropriate
      management by detecting and differentiating expected CTA findings from
      complications.

PMID- 19155420
TI  - Idiopathic chondrolysis of the hip in children: early MRI findings.
AB  - OBJECTIVE: The objective of our study was to identify the early MRI findings
      characteristic of idiopathic chondrolysis of the hip in children. CONCLUSION: A
      geometric region of abnormal signal intensity centered in the proximal femoral
      epiphysis, accompanied by ipsilateral ill-defined acetabular bone marrow edema,
      mild synovial hypertrophy, and minimal if any joint fluid, in a child with a
      painful stiff hip are early MRI findings characteristic of idiopathic
      chondrolysis.

PMID- 19155421
TI  - CT detection of subendocardial fat in myocardial infarction.
AB  - OBJECTIVE: We sought to systemically analyze the characteristics of fat
      accumulation in patients with myocardial infarction (MI) relative to various
      clinical parameters. MATERIALS AND METHODS: We included 161 patients (129 men, 32
      women; mean age, 60.7 years) who had previously been diagnosed with MI and had
      undergone CT coronary angiography between February 2003 and April 2005. We
      analyzed the characteristics of myocardial fat, if present, and compared the
      clinical parameters of the patients with and those without myocardial fat.
      RESULTS: Myocardial fat was found in the subendocardial region in 36 (22.4%)
      patients with MI. In all cases, the myocardial fat was located in the
      subendocardial region and was typically detected in the left anterior descending
      artery territory (75%, n = 27). The mean attenuation value of myocardial fat was 
      29.6 HU on unenhanced CT. Myocardial fat was more frequently associated with a
      greater infarct age, milder coronary artery stenosis, and fewer number of
      diseased vessels. Patients with myocardial fat had more severe regional wall
      motion abnormalities on follow-up echocardiography. Age, sex, the presence of ST
      elevation or Q wave, elevated levels of cardiac enzymes, ejection fraction, and
      end-diastolic left ventricular dimension on follow-up echocardiography, as well
      as the presence of arrhythmia, were not significantly different between the two
      groups. CONCLUSION: Myocardial fat was detected in 22.4% of MI patients and was
      more frequently associated with a longer postinfarct period, milder coronary
      artery stenosis, fewer number of diseased vessels, and more severe regional wall
      motion abnormalities.

PMID- 19155422
TI  - Preparing first-year radiology residents and assessing their readiness for on
      call responsibilities: results over 5 years.
AB  - OBJECTIVE: The objective of our study was to evaluate the preparedness of
      postgraduate year (PGY)-2 residents for independent call responsibilities and the
      impact of the radiology residency training program on call preparedness using an
      objective DICOM-based simulation module over a 5-year period. MATERIALS AND
      METHODS: A month-long emergency radiology lecture series, conducted over 5
      consecutive years, was designed and given to radiology residents at all levels. A
      DICOM-based, interactive, computer-based testing module with actual emergency
      department cases was developed and administered at the end of the lecture series.
      Comparison was made between first-year and upper-level resident test scores using
      a Student's t test, generalized estimating equations, and individual fixed
      effects to determine PGY-2 residents' before-call preparedness and the
      effectiveness of the simulation module to assess call preparedness. Resident
      scoring on the simulation module was also plotted as a function of progression
      through their residency program to evaluate the impact of the training program on
      call preparedness. RESULTS: Over 5 years, 45 PGY-2, 34 PGY-3, 32 PGY-4, and 35
      PGY-5 residents attended the lecture series and completed the computer-based
      testing module. PGY-2 residents scored an average of 71% +/- 15% (SD), PGY-3
      residents scored 79% +/- 11%, PGY-4 residents scored 84% +/- 10%, and PGY-5
      residents scored 86% +/- 11% of the total points possible. A statistically
      significant (p < 0.05) difference in scoring on the simulation module was
      identified between the PGY-2 residents and each upper-level class over the 5-year
      period and during 4 of 5 examination years analyzed separately. A trend toward
      higher average scores for each cohort of residents as they progressed through
      residency training was identified. CONCLUSION: Over a 5-year period, first-year
      radiology residents scored significantly lower than upper-level colleagues on an
      emergency radiology simulation module, suggesting a significant improvement in
      the ability of residents to interpret typical on-call imaging studies after the
      PGY-2 year.

PMID- 19155423
TI  - Motivated cultural worldview adherence and culturally loaded test performance.
AB  - Academic tests and their conditions of administration are culturally loaded when
      they make salient culturally specific knowledge structures in addition to
      measuring the intended cognitive ability. Cultural loading demonstrably
      influences test performance, but why? Drawing on converging perspectives on the
      psychological function of culture, this article proposes that one factor is the
      individual's internal motivation to affirm and uphold the cultural worldview.
      This possibility is tested within the framework of terror management theory,
      which claims that cultural worldview adherence defends against mortality-related
      concerns. It is hypothesized that making mortality salient would (a) improve
      performance on standardized test items when, incidental to the problem structure,
      the correct answers affirm prevailing cultural stereotypes and (b) impair test
      performance when excelling violates stereotypic expectancies for one's group. Two
      studies provide support for these hypotheses. Implications for test validity are
      briefly discussed.

PMID- 19155425
TI  - Differences between dietary supplement and prescription drug omega-3 fatty acid
      formulations: a legislative and regulatory perspective.
AB  - The medical management of many diseases and conditions can include either
      restriction or provision of specific essential nutrients. When such nutrients are
      needed, there are often both prescription and nonprescription products available,
      as in the case of nicotinic acid or omega-3 fatty acids. Although they may seem
      to contain similar ingredients, there may be important differences between the
      prescription and dietary-supplement preparations. The manufacturing of
      prescription pharmaceutical products is regulated by the US Food and Drug
      Administration (FDA), which mandates standards for consistency and quality
      assurance. Dietary supplements are available to consumers under the provisions of
      the Dietary Supplement Health and Education Act of 1994, for which the FDA has
      the burden of proving a dietary supplement is harmful rather than requiring the
      manufacturer prove that the supplement is safe. Consumers and medical
      professionals should be aware of the important qualitative and quantitative
      differences between the FDA-approved prescription formulations and dietary
      supplements, particularly when an essential nutrient is part of the medical
      management of a disease or condition.

PMID- 19155426
TI  - Nonalcoholic fatty liver disease in children.
AB  - In view of the epidemic obesity in childhood, facing the disease and its
      associated morbidities early at this age becomes crucial for public health
      researchers and care givers. The present review focuses on pediatric Non
      Alcoholic Fatty Liver Disease (NAFLD) among co-morbidities, being the disease yet
      under diagnosed and under treated despite a prevalence growing exponentially.
      Evidences suggest that the environmental background for the development of NAFLD
      may be established in early life, and that the duration of the disease affects
      probably the likelihood of progression to more severe disease (necro-inflammation
      or Non Alcoholic SteatoHepatitis, also termed, NASH; fibrosis and cirrhosis).
      NAFLD associates with abdominal obesity, insulin resistance and features of
      metabolic syndrome. In genetically prone individuals, malnutrition (i.e.,
      excessive consumption of saturated fats and refined sugars) leads to the
      derangement of the adipose tissue architecture and homeostasis, the peripheral
      and hepatic resistance to insulin-stimulated glucose uptake, thus favoring a
      condition of chronic low-grade inflammation. Excessive nutrients cannot be stored
      in the adipose tissue and overflow elsewhere, mainly to the muscle tissue and
      liver. Fat deposition in both sites enhances insulin resistance and further
      deposition of fats in a vicious manner. What is of special interest comparing
      NAFLD in children and adults is that the histological appearance of the disease
      differs significantly, likely representing a yet physiological response to
      environmental stressors in children and a long-term adaptation in adults. In this
      article, we review the current concepts about paediatric NAFLD, its pathogenesis,
      diagnosis and treatment, with particular regard to lifestyle and foods habits.

PMID- 19155427
TI  - Honey for nutrition and health: a review.
AB  - Due to the variation of botanical origin honey differs in appearance, sensory
      perception and composition. The main nutritional and health relevant components
      are carbohydrates, mainly fructose and glucose but also about 25 different
      oligosaccharides. Although honey is a high carbohydrate food, its glycemic index
      varies within a wide range from 32 to 85, depending on the botanical source. It
      contains small amounts of proteins, enzymes, amino acids, minerals, trace
      elements, vitamins, aroma compounds and polyphenols. The review covers the
      composition, the nutritional contribution of its components, its physiological
      and nutritional effects. It shows that honey has a variety of positive
      nutritional and health effects, if consumed at higher doses of 50 to 80 g per
      intake.

PMID- 19155428
TI  - Vitamin D supplementation during lactation to support infant and mother.
AB  - How human milk as the ideal infant nutrition lacks vitamin D activity leading to
      the severe bony deformities and muscle weakness of rickets has stymied scientists
      and clinicians for centuries. Recent understanding of human vitamin D
      requirements based on functional indicators of vitamin D activity demonstrate
      that the majority of humans, including lactating mothers, subsist in a vitamin D
      insufficient state. In this state, human milk provides inadequate vitamin D
      supply to the nursing infant. In contrast, with achieving maternal vitamin D
      sufficiency, human milk attains vitamin D activity equivalent to present infant
      oral supplementation. Current investigation of the role of vitamin D in diseases
      beyond bone health is revealing the significance of early life vitamin D
      sufficiency in establishing lifelong health.

PMID- 19155429
TI  - Dairy intake and anthropometric measures of body fat among children and
      adolescents in NHANES.
AB  - OBJECTIVE: To explore the relation between dairy intake and body fat among
      children and adolescents. MATERIALS AND METHODS: Children (5-11 years) and
      adolescents (12-16 years) were included who had data on diet, anthropometry
      measures of body fat, and relevant potential confounders (children: n = 3,864 and
      2,231; adolescents: n = 1,884 and 2,636 in NHANES III and NHANES 1999-2002,
      respectively). Each child's daily dairy intake from 24-hour recalls was
      classified as low, moderate or high. For girls and boys, respectively: low
      intake: <1 and <2 servings; moderate intake: 1-<3 and 2-<4 servings; and high
      intake: >or=3 and >or=4 servings per day.) Analysis of covariance was used to
      control for potential confounding by age, gender, socio-economic status,
      race/ethnicity, height and television watching. RESULTS: Among children, there
      was no consistent association between dairy intake and anthropometric indices of
      body fat. Among adolescents, the lowest dairy intake group (< one serving per day
      for girls and < two per day for boys) had higher estimated levels of body fat
      than those in the highest dairy group. Compared with the lowest intake level,
      adolescent girls in NHANES III who consumed 1-<3 servings per day of dairy had
      about 2.5 mm less subcutaneous body fat (95% CI: -4.70 mm, -0.39 mm) while girls
      consuming three or more servings had about 5 mm less fat in their sum of two
      skinfolds. Adolescent boys consuming 4 or more servings of dairy per day had
      lower anthropometry levels than did those consuming less than two servings.
      CONCLUSION: Among adolescents, suboptimal dairy intake was associated with higher
      anthropometric measures of body fat.

PMID- 19155430
TI  - Effect of novel maize-based dietary fibers on postprandial glycemia and
      insulinemia.
AB  - BACKGROUND: Postprandial hyperglycemia has been associated with increased
      oxidative stress and the development of diabetes, heart disease and all-cause
      mortality. OBJECTIVE: To assess the effect of novel maize-based dietary fibers on
      postprandial glycemia and to assess the correlation between a rapid in vitro
      digestibility system and the blood glucose response. METHODS: In a clinical
      study, 12 healthy volunteers were fed seven test beverages containing maize-based
      fiber ingredients (25g total carbohydrate) along with 2 control meals on separate
      occasions in random order. Capillary blood samples were obtained and the relative
      glycemic and insulinemic responses were assessed by calculating the incremental
      area under the 2 h blood response curves. In vitro digestibility studies of the
      test fibers and control were also undertaken to determine if these correlated
      with the clinical findings. RESULTS: All test fibers resulted in significantly
      lower glycemic and insulinemic responses for the incremental area under the curve
      (iAUC) and at all time points compared with the control (P < 0.05). The in vitro
      digestibility curves were comparable to the cumulative in vivo iAUCs. In vitro
      data expressed as percent digestion correlated significantly with the in vivo
      iAUC for the first 30min of the test meal (P < 0.05). CONCLUSION: These novel
      maize-based dietary fibers all produce lower postprandial glycemic and
      insulinemic responses than the control. While further assessment is necessary in
      beverage and foods containing these fibers, they may be effective in applications
      for dietary strategies to control diabetes and other chronic diseases. In
      addition, the in vitro digestibility assay correlated well with in vivo data and
      may be useful in guiding product development.

PMID- 19155431
TI  - Introduction to the proceedings of the symposium "Scientific Update on Dairy Fats
      and Cardiovascular Diseases".

PMID- 19155432
TI  - The survival advantage of milk and dairy consumption: an overview of evidence
      from cohort studies of vascular diseases, diabetes and cancer.
AB  - OBJECTIVES: To conduct a detailed evaluation, with meta-analyses, of the
      published evidence on milk and dairy consumption and the incidence of vascular
      diseases and diabetes. Also to summarise the evidence on milk and dairy
      consumption and cancer reported by the World Cancer Research Fund and then to
      consider the relevance of milk and dairy consumption to survival in the UK, a
      typical Western community. Finally, published evidence on relationships with
      whole milk and fat-reduced milks was examined. METHODS: Prospective cohort
      studies of vascular disease and diabetes with baseline data on milk or dairy
      consumption and a relevant disease outcome were identified by searching MEDLINE,
      and reference lists in the relevant published reports. Meta-analyses of
      relationships in these reports were conducted. The likely effect of milk and
      dairy consumption on survival was then considered, taking into account the
      results of published overviews of relationships of these foods with cancer.
      RESULTS: From meta-analysis of 15 studies the relative risk of stroke and/or
      heart disease in subjects with high milk or dairy consumption was 0.84 (95% CI
      0.76, 0.93) and 0.79 (0.75, 0.82) respectively, relative to the risk in those
      with low consumption. Four studies reported incident diabetes as an outcome, and
      the relative risk in the subjects with the highest intake of milk or diary foods
      was 0.92 (0.86, 0.97). CONCLUSIONS: Set against the proportion of total deaths
      attributable to the life-threatening diseases in the UK, vascular disease,
      diabetes and cancer, the results of meta-analyses provide evidence of an overall
      survival advantage from the consumption of milk and dairy foods.

PMID- 19155433
TI  - Effects of dairy fats within different foods on plasma lipids.
AB  - This review considers within the epidemiology of dairy fats and cardiovascular
      risk including the effects of 1. Fats within different dairy foods, 2. Specific
      dairy fatty acids including ruminant trans fats (TFA), conjugated linoleic acid
      (CLA), myristic acid and 3. The influence of metabolic syndrome.

PMID- 19155434
TI  - Review of the effect of dairy products on non-lipid risk factors for
      cardiovascular disease.
AB  - The association between dairy food consumption and the risk of cardiovascular
      disease (CVD) has been a topic of intense debate over the years. Recent data
      suggest that individuals who consume dairy foods, particularly low fat products,
      are less likely to develop CVD than those who have a lower intake of these foods.
      We are also just beginning to understand how various components of the complex
      dairy food matrix affect several risk factors for CVD. The objective of this
      review is to provide an overview of the effects of dairy foods per se and of some
      of their components on non lipid CVD risk factors. Focus will be on blood
      pressure, inflammation, insulin resistance and type 2 diabetes, obesity and the
      metabolic syndrome. While the impact of dairy foods on blood pressure appears to
      be beyond debate, their effects on body weight and other non lipid risk factors
      need to be further substantiated. However, the purported inverse association
      between dairy foods, particularly low fat dairy products, and the metabolic
      syndrome is suggestive of cardiovascular benefits that may go well beyond the
      effect of dairy fat on blood cholesterol.

PMID- 19155435
TI  - Dairy products as essential contributors of (micro-) nutrients in reference food
      patterns: an outline for elderly people.
AB  - The nutrient richness of dairy products is widely recognized, but mainly low fat
      or skimmed versions are generally advocated given the proportion of saturated
      fatty acids in milk fat. The question arises how to appraise this nutrient
      richness relative to the contribution of the saturated fraction of dairy fat. We
      reviewed available data--collected from elderly people--on nutrient contributions
      by dairy products in The Netherlands, on the relevance of nutrients specifically
      supplied by dairy products and shown to be associated with ageing-related
      functional losses, and from prospective studies in selected elderly populations
      in Europe on the impact of dietary and lifestyle factors on morbidity and
      mortality. In the current daily food pattern of older adults in The Netherlands
      dairy products provide significant to substantial amounts of protein and a number
      of minerals and vitamins relevant for healthy ageing. Especially in the frail
      elderly it will be difficult to replace dairy products by other foods. Dietary
      advice should focus on an adequate supply of energy, protein and micronutrients
      rather than on avoiding saturated fats. For the younger healthy 65 + we estimated
      that including lower fat dairy products rather their whole fat equivalents, may
      help to improve the dietary pattern. However, prospective analyses on morbidity
      and mortality do not suggest that moderate dietary intake of dairy products is
      associated with increased cardiovascular disease risk in this age group. In
      dietary risk-benefit analyses the ultimate perspective should be the nutritional
      status, the risk profile of the target group and the place of the foods in the
      dietary pattern. Such analyses need more sophisticated methods than currently
      available and applied in this paper. In Europe initiatives have been taken to
      develop such methods.

PMID- 19155436
TI  - Thyroid function and cancer risk: a prospective population study.
AB  - BACKGROUND: It has been hypothesized that thyroid function may influence cancer
      risk, but few studies with adequate statistical power have investigated this
      question, and the results have not been consistent. METHODS: In a prospective
      study of 29,691 people (19,710 women and 9,981 men) without previously known
      thyroid disease, thyrotropin was measured at baseline, and cancer incidence was
      recorded during 9 years of follow-up. Using Cox regression analysis, we studied
      the associations (hazard ratios) of thyrotropin categories with total cancer
      risk, and specifically, with risk of lung, colon, prostate, and breast cancer
      adjusted for age, sex, and smoking status. RESULTS: Low thyrotropin levels (<0.50
      mU/L) were associated with increased cancer risk [adjusted hazard ratio (HR),
      1.34; 95% confidence interval (CI), 1.06-1.69] compared with the euthyroid
      reference group. The higher risk was driven by lung cancer (adjusted HR, 2.34;
      95% CI, 1.24-4.40) and prostate cancer (adjusted HR, 1.97; 95% CI, 1.04-3.76).
      After excluding the first 2 years of follow-up, the associations were
      strengthened to 2.91 (1.49-5.70) for lung cancer and 2.60 (1.36-4.99) for
      prostate cancer. CONCLUSION: Thyrotropin levels suggestive of hyperthyroid
      function are associated with increased cancer risk, and specifically, with
      increased risk of lung and prostate cancer, whereas hypothyroid function does not
      seem to be associated with cancer risk.

PMID- 19155437
TI  - Staphylococcus aureus and squamous cell carcinoma of the skin.
AB  - Squamous cell carcinoma (SCC) of the skin is a tumor with greatly increased
      incidence among immunosuppressed patients; therefore, an infectious cause of SCC
      has long been sought. We performed a hospital-based case-control study of
      Staphylococcus aureus and biopsies of SCC (n = 82), basal cell carcinoma (n =
      142), actinic keratosis (n = 57), and seborrhoeic keratosis (n = 72) in
      comparison with biopsies from healthy skin of these 353 immunocompetent patients.
      In a S. aureus-specific PCR, targeting the nuc gene, presence of S. aureus DNA
      was strongly associated with SCC (29.3% positive specimens; adjusted odds ratio,
      6.23; 95% confidence interval, 3.10-12.53) compared with healthy skin (5.7%
      positive specimens). There was also a tendency for association of S. aureus with
      actinic keratosis, but no association was found for basal cell carcinoma or
      seborrhoeic keratosis. Analysis using cotton swab samples taken on top of the
      lesions and from healthy skin gave similar results (adjusted odds ratio for SCC
      compared with healthy skin, 2.67; 95% confidence interval, 1.47-4.83). In
      conclusion, there is a strong association between SCC and presence of S. aureus.
      The study design used cannot determine whether the association implies that
      presence of S. aureus might influence carcinogenesis or whether it may imply that
      SCC has an increased susceptibility to S. aureus colonization.

PMID- 19155439
TI  - Overexpression of EIF-5A2 is an independent predictor of outcome in patients of
      urothelial carcinoma of the bladder treated with radical cystectomy.
AB  - BACKGROUND: Our previous study has suggested an oncogenic role of eIF-5A2 in
      ovarian tumorigenesis. Abnormalities of eIF-5A2 and its clinical/prognostic
      significance, however, in urothelial carcinoma of the bladder (UC) are unclear.
      METHODS: In this study, the methods of reverse transcription-PCR,
      immunohistochemistry, and fluorescence in situ hybridization were used to examine
      mRNA/protein expression and amplification of eIF-5A2 in a large cohort of UCs
      treated with radical cystectomy. RESULTS: Up-regulated expression of eIF-5A2 mRNA
      was observed in 50% (8 of 16) of UCs, when compared with adjacent normal bladder
      tissues. Overexpression of EIF-5A2 protein and amplification of eIF-5A2 was
      examined informatively in 45.3% (39 of 86) and 10.6% (5 of 47) of UCs,
      respectively. In univariate survival analysis of the UC cohorts, a significant
      association of overexpression of EIF-5A2 with shortened patient survival (mean,
      38.2 months versus 52.9 months, P = 0.001, log-rank test) was shown. In different
      subsets of UC patients, overexpression of EIF-5A2 was also a prognostic indicator
      in grade 1/2 (P = 0.0009) and grade 3 (P = 0.016) tumor patients, and in pT1 (P =
      0.0089), pT2 (P = 0.0354), pT3/4 (P = 0.0058), pN0 (P = 0.0039), and pN1-2 (P =
      0.0093) tumor patients. Importantly, EIF-5A2 expression (P = 0.0007) together
      with pT stage (P = 0.0001) provided significant independent prognostic variables
      in multivariate analysis. CONCLUSIONS: These findings indicate that
      overexpression of EIF-5A2 in UCs is coincident with acquisition of a poor
      prognostic phenotype, suggesting that the expression of EIF-5A2, as detected by
      immunohistochemistry, is an independent molecular marker for shortened survival
      time of UC patients treated with radical cystectomy.

PMID- 19155440
TI  - Meta association of colorectal cancer confirms risk alleles at 8q24 and 18q21.
AB  - BACKGROUND: Genome-wide association studies of colorectal cancer (CRC) have
      identified genetic variants that reproducibly associate with CRC. Associations of
      12 single nucleotide polymorphisms at 8q24, 9p24, and 18q21 (SMAD7) and CRC were
      investigated in a three-center collaborative study including two U.K. case
      control cohorts (Sheffield and Leeds) and a U.S. case-control study of CRC cases
      from high-risk Utah pedigrees. METHODS: Our combined resource included 1,092 CRC
      case subjects and 1,060 age- and sex-matched controls. Meta statistics and Monte
      Carlo significance testing using Genie software provided a valid combined
      analysis of our mixed independent and related case-control resource. We also
      evaluated whether these associations differed by sex, age at diagnosis, family
      history, or tumor site. RESULTS: At 8q24, we observed two independent significant
      associations at single nucleotide polymorphisms located in two different risk
      regions of 8q24: rs6983267 in region 3 [P(trend) = 0.01; per allele odds ratio
      (OR), 1.17; 95% confidence intervals (95% CI), 1.03-1.32] and rs10090154 in
      region 5 (P(trend) = 0.05; per allele OR, 1.24; 95% CI, 1.01-1.51). At 18q21,
      associations were observed in distal colon tumors but not in proximal or rectal
      cancers: rs4939827 (P(trend) = 0.007; per allele OR, 0.77; 95% CI, 0.64-0.93;
      case-case p(diff) = 0.03) and rs12953717 (P(trend) = 0.01; per allele OR, 1.27;
      95% CI, 1.06-1.52). We were unable to detect any associations at 9p24 with CRC.
      CONCLUSIONS: Our investigation confirms that variants across multiple risk
      regions of 8q24 are associated with CRC, and that associations at 18q21 differ by
      tumor site.

PMID- 19155438
TI  - Aberrant cytoplasmic expression of p63 and prostate cancer mortality.
AB  - Protein expression of p63 is used to differentiate prostate cancer from benign
      mimickers. Recent studies suggest that it may also distinguish aggressive
      prostate cancer with down-regulated expression occurring in men with more
      advanced disease. We conducted a prospective study among 298 men ages 51 to 84
      years who were diagnosed with prostate cancer in the Physicians' Health Study in
      1983 to 2004 and whose tissue was available for immunohistochemical staining. We
      used Cox proportional hazards regression to evaluate the association of p63
      protein expression with fatal prostate cancer. We correlated p63 expression with
      tumor cell proliferation (Ki-67) and apoptosis (TUNEL staining). The predominant
      location of tumor p63 staining occurred in the cytoplasm, an uncommon departure
      from the strong nuclear staining usually observed in nonneoplastic basal cells.
      Increasing expression of cytoplasmic p63 (tertiles) was associated with prostate
      cancer mortality (n = 19 deaths); the hazard ratios (95% confidence intervals)
      were 1.0 (reference), 4.0 (0.9-18.9), and 5.9 (1.3-27.5; P(trend) = 0.03). The
      positive trend remained significant (P = 0.047) after multivariable adjustment
      for age, year of diagnosis, and Gleason score. Higher tertiles of cytoplasmic p63
      were also associated with reduced levels of apoptosis (P(trend) = 0.0408) and
      increased cellular proliferation (P(trend) = 0.0026). We found aberrant
      expression of p63 in the cytoplasm to be associated with increased prostate
      cancer-specific mortality up to 20 years after diagnosis. The mislocalized
      expression was associated with reduced apoptosis and higher proliferative
      activity and may suggest an oncogenic role in prostate cancer progression and
      survival.

PMID- 19155441
TI  - High clusterin expression correlates with a poor outcome in stage II colorectal
      cancers.
AB  - The role of clusterin in tumor growth and progression remains unclear.
      Overexpression of cytoplasmic clusterin has been studied in aggressive colon
      tumors; however, no correlation between clusterin expression and survival in
      colorectal cancer has been identified to date. We assessed levels of clusterin
      expression in a group of stage II colorectal cancer patients to assess its
      utility as a prognostic marker. The study included 251 patients with stage II
      colorectal cancer. Tissue microarrays were constructed and immunohistochemistry
      done and correlated with clinical features and long term outcome. Dual
      immunofluorescence and confocal microscopy were used with terminal
      deoxynucleotidyl-transferase-mediated dUTP nick-end labeling probes and clusterin
      antibody to assess the degree of co localization. Percentage epithelial
      cytoplasmic staining was higher in tumor compared with nonadjacent normal mucosa
      (P < 0.001). Within the stromal compartment, percentage cytoplamic staining and
      intensity was lower in tumor tissue compared with normal nonadjacent mucosa (P <
      or = 0.001). Survival was significantly associated with percentage epithelial
      cytoplasmic staining (P < 0.001), epithelial cytoplasmic staining intensity (P <
      0.001), percentage stromal cytoplasmic staining (P = 0.002), and stromal
      cytoplasmic staining intensity (P < 0.001). Clusterin levels are associated with
      poor survival in stage II colorectal cancer.

PMID- 19155442
TI  - Price dynamics in political prediction markets.
AB  - Prediction markets, in which contract prices are used to forecast future events,
      are increasingly applied to various domains ranging from political contests to
      scientific breakthroughs. However, the dynamics of such markets are not well
      understood. Here, we study the return dynamics of the oldest, most data-rich
      prediction markets, the Iowa Electronic Presidential Election "winner-takes-all"
      markets. As with other financial markets, we find uncorrelated returns, power-law
      decaying volatility correlations, and, usually, power-law decaying distributions
      of returns. However, unlike other financial markets, we find conditional
      diverging volatilities as the contract settlement date approaches. We propose a
      dynamic binary option model that captures all features of the empirical data and
      can potentially provide a tool with which one may extract true information events
      from a price time series.

PMID- 19155444
TI  - The cover. Watching.

PMID- 19155445
TI  - A piece of my mind. Part-time medicine.

PMID- 19155443
TI  - A gamma-tocopherol-rich mixture of tocopherols inhibits colon inflammation and
      carcinogenesis in azoxymethane and dextran sulfate sodium-treated mice.
AB  - We investigated the effects of a gamma-tocopherol-rich mixture of tocopherols
      (gamma-TmT, containing 57% gamma-T, 24% delta-T, and 13% alpha-T) on colon
      carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice.
      In experiment 1, 6-week-old male CF-1 mice were given a dose of AOM (10 mg/kg
      body weight, i.p.), and 1 week later, 1.5% DSS in drinking water for 1 week. The
      mice were maintained on either a gamma-TmT (0.3%)-enriched or a standard AIN93M
      diet, starting 1 week before the AOM injection, until the termination of
      experiment. In the AOM/DSS-treated mice, dietary gamma-TmT treatment resulted in
      a significantly lower colon inflammation index (52% of the control) on day 7 and
      number of colon adenomas (9% of the control) on week 7. gamma-TmT treatment also
      resulted in higher apoptotic index in adenomas, lower prostaglandin E2,
      leukotriene B4, and nitrotyrosine levels in the colon, and lower prostaglandin
      E2, leukotriene B4, and 8-isoprostane levels in the plasma on week 7. Some of the
      decreases were observed even on day 7. In experiment 2 with AOM/DSS- treated mice
      sacrificed on week 21, dietary 0.17% or 0.3% gamma-TmT treatment, starting 1 week
      before the AOM injection, significantly inhibited adenocarcinoma and adenoma
      formation in the colon (to 17-33% of the control). Dietary 0.3% gamma-TmT that
      was initiated after DSS treatment also exhibited a similar inhibitory activity.
      The present study showed that gamma-TmT effectively inhibited colon
      carcinogenesis in AOM/DSS-treated mice, and the inhibition may be due to the
      apoptosis-inducing, anti-inflammatory, antioxidative, and reactive nitrogen
      species-trapping activities of tocopherols.

PMID- 19155446
TI  - IOM: Shorten residents' work shifts to reduce fatigue, improve patient safety.

PMID- 19155447
TI  - Researchers worry about myopathy risk for patients taking high-dose simvastatin.

PMID- 19155448
TI  - Allopurinol and the role of uric acid in hypertension.

PMID- 19155449
TI  - Metal content in Ayurvedic medicines.

PMID- 19155450
TI  - Physical activity and cognitive function in Alzheimer disease.

PMID- 19155451
TI  - Physical activity and cognitive function in Alzheimer disease.

PMID- 19155452
TI  - CDC recommendations for opt-out HIV testing.

PMID- 19155453
TI  - CDC recommendations for opt-out HIV testing.

PMID- 19155454
TI  - Effect of preventive supplementation with ready-to-use therapeutic food on the
      nutritional status, mortality, and morbidity of children aged 6 to 60 months in
      Niger: a cluster randomized trial.
AB  - CONTEXT: Ready-to-use therapeutic foods (RUTFs) are an important component of
      effective outpatient treatment of severe wasting. However, their effectiveness in
      the population-based prevention of moderate and severe wasting has not been
      evaluated. OBJECTIVE: To evaluate the effect of a 3-month distribution of RUTF on
      the nutritional status, mortality, and morbidity of children aged 6 to 60 months
      in Niger. DESIGN, SETTING, AND PARTICIPANTS: A cluster randomized trial of 12
      villages in Maradi, Niger. Six villages were randomized to intervention and 6 to
      no intervention. All children in the study villages aged 6 to 60 months were
      eligible for recruitment. INTERVENTION: Children with weight-for-height 80% or
      more of the National Center for Health Statistics reference median in the 6
      intervention villages received a monthly distribution of 1 packet per day of RUTF
      (92 g [500 kcal/d]) from August to October 2006. Children in the 6
      nonintervention villages received no preventive supplementation. Active
      surveillance for conditions requiring medical or nutritional treatment was
      conducted monthly in all 12 study villages from August 2006 to March 2007. MAIN
      OUTCOME MEASURES: Changes in weight-for-height z score (WHZ) according to the
      World Health Organization Child Growth Standards and incidence of wasting (WHZ <
      2) over 8 months of follow-up. RESULTS: The number of children with height and
      weight measurements in August, October, December, and February was 3166, 3110,
      2936, and 3026, respectively. The WHZ difference between the intervention and
      nonintervention groups was -0.10 z (95% confidence interval [CI], -0.23 to 0.03)
      at baseline and 0.12 z (95% CI, 0.02 to 0.21) after 8 months of follow-up. The
      adjusted effect of the intervention on WHZ from baseline to the end of follow-up
      was thus 0.22 z (95% CI, 0.13 to 0.30). The absolute rate of wasting and severe
      wasting, respectively, was 0.17 events per child-year (140 events/841 child
      years) and 0.03 events per child-year (29 events/943 child-years) in the
      intervention villages, compared with 0.26 events per child-year (233 events/895
      child-years) and 0.07 events per child-year (71 events/1029 child-years) in the
      nonintervention villages. The intervention thus resulted in a 36% (95% CI, 17% to
      50%; P < .001) reduction in the incidence of wasting and a 58% (95% CI, 43% to
      68%; P < .001) reduction in the incidence of severe wasting. There was no
      reduction in mortality, with a mortality rate of 0.007 deaths per child-year (7
      deaths/986 child-years) in the intervention villages and 0.016 deaths per child
      year (18 deaths/1099 child-years) in the nonintervention villages (adjusted
      hazard ratio, 0.51; 95% CI, 0.25 to 1.05). CONCLUSION: Short-term supplementation
      of nonmalnourished children with RUTF reduced the decline in WHZ and the
      incidence of wasting and severe wasting over 8 months. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00682708.

PMID- 19155455
TI  - Left ventricular function and exercise capacity.
AB  - CONTEXT: Limited information exists regarding the role of left ventricular
      function in predicting exercise capacity and impact on age- and sex-related
      differences. OBJECTIVES: To determine the impact of measures of cardiac function
      assessed by echocardiography on exercise capacity and to determine if these
      associations are modified by sex or advancing age. DESIGN: Cross-sectional study
      of patients undergoing exercise echocardiography with routine measurements of
      left ventricular systolic and diastolic function by 2-dimensional and Doppler
      techniques. Analyses were conducted to determine the strongest correlates of
      exercise capacity and the age and sex interactions of these variables with
      exercise capacity. SETTING: Large tertiary referral center in Rochester,
      Minnesota, in 2006. PARTICIPANTS: Patients undergoing exercise echocardiography
      using the Bruce protocol (N = 2867). Patients with echocardiographic evidence of
      exercise-induced ischemia, ejection fractions lower than 50%, or significant
      valvular heart disease were excluded. MAIN OUTCOME MEASURE: Exercise capacity in
      metabolic equivalents (METs). RESULTS: Diastolic dysfunction was strongly and
      inversely associated with exercise capacity. Compared with normal function, after
      multivariate adjustment, those with moderate/severe resting diastolic dysfunction
      (-1.30 METs; 95% confidence interval [CI], -1.52 to -0.99; P < .001) and mild
      resting diastolic dysfunction (-0.70 METs; 95% CI, -0.88 to -0.46; P < .001) had
      substantially lower exercise capacity. Variation of left ventricular systolic
      function within the normal range was not associated with exercise capacity. Left
      ventricular filling pressures measured by resting E/e' of 15 or greater (-0.41
      METs; 95% CI, -0.70 to -0.11; P = .007) or postexercise E/e' of 15 or greater (
      0.41 METs; 95% CI, -0.71 to -0.11; P = .007) were similarly associated with a
      reduction in exercise capacity, each in separate multivariate analyses.
      Individuals with impaired relaxation (mild dysfunction) or resting E/e' of 15 or
      greater had a progressive increase in the magnitude of reduction in exercise
      capacity with advancing age (P < .001 and P = .02, respectively). Other
      independent correlates of exercise capacity were age (unstandardized beta
      coefficient, -0.85 METs; 95% CI, -0.92 to -0.77, per 10-year increment; P <
      .001), female sex (-1.98 METs; 95% CI, -2.15 to -1.84; P < .001), and body mass
      index greater than 30 (-1.24 METs; 95% CI, -1.41 to -1.10; P < .001). CONCLUSION:
      In this large cross-sectional study of those referred for exercise
      echocardiography and not limited by ischemia, abnormalities of left ventricular
      diastolic function were independently associated with exercise capacity.

PMID- 19155457
TI  - How to use an article about genetic association: C: What are the results and will
      they help me in caring for my patients?
AB  - In the first 2 articles of this series, we reviewed the basic genetics concepts
      necessary to understand genetic association studies, and we enumerated the major
      issues in judging the validity of these studies. In this third article, we review
      the issues relating to the applicability of the results in the clinical
      situation. How large and precise are the associations? Many genetic effects are
      expected to be smaller in magnitude than traditional risk factors. Does the
      genetic association improve predictive power beyond easily measured clinical
      variables? In some cases, the additional genetic information adds only a small
      increment in the predictive ability of a diagnostic or prognostic test. What are
      the absolute vs relative effects? Even if the genetic risk is high in relative
      terms, the baseline risk may be very low in absolute terms. Is the risk
      associated allele likely to be present in my patient? A risk allele may have a
      strong effect but be rare in a particular ethnic group. Is the patient likely
      better off knowing the genetic information? Given that genes cannot be modified,
      one must weigh whether the genetic information is likely to be helpful in
      planning other health interventions or initiating behavior change.

PMID- 19155456
TI  - Escitalopram for older adults with generalized anxiety disorder: a randomized
      controlled trial.
AB  - CONTEXT: Generalized anxiety disorder (GAD) is one of the most common psychiatric
      disorders in older adults; however, few data exist to guide clinicians in
      efficacious and safe treatment. Selective serotonin reuptake inhibitors (SSRIs)
      are efficacious for younger adults with GAD, but benefits and risks may be
      different in older adults. OBJECTIVE: To examine the efficacy, safety, and
      tolerability of the SSRI escitalopram in older adults with GAD. DESIGN, SETTING,
      AND PARTICIPANTS: A randomized controlled trial in primary care practices and
      related specialty clinics in Pittsburgh, Pennsylvania, of 177 participants aged
      60 years or older with a principal diagnosis of GAD randomized to receive either
      escitalopram or placebo and conducted between January 2005 and January 2008.
      INTERVENTIONS: Twelve weeks of 10 to 20 mg/d of escitalopram (n = 85) or matching
      placebo (n = 92). MAIN OUTCOME MEASURES: Cumulative response defined by Clinical
      Global Impressions-Improvement score of much or very much improved; time to
      response; and anxiety and role functioning changes measured by the Clinical
      Global Impressions-Improvement scale, Hamilton Anxiety Rating Scale, Penn State
      Worry Questionnaire, Late-Life Function and Disability Instrument activity
      limitations subscale, and the role-emotional impairment and social function
      subscales of the Medical Outcome Survey 36-item Short Form. RESULTS: In the
      primary analytic strategy in which participants (n = 33) were censored at the
      time of dropout, mean cumulative response rate for escitalopram was 69% (95%
      confidence interval [CI], 58%-80%) vs 51% (95% CI, 40%-62%) for placebo (P =
      .03). A conservative intention-to-treat analysis showed no difference in mean
      cumulative response rate between escitalopram and placebo (57%; 95% CI, 46%-67%;
      vs 45%; 95% CI, 35%-55%; P = .11). Participants treated with escitalopram showed
      greater improvement than with placebo in anxiety symptoms and role functioning
      (Clinical Global Impressions-Improvement scale: effect size, 0.93; 95% CI, 0.50
      1.36; P < .001; Penn State Worry Questionnaire: 0.30; 95% CI, 0.23-0.48; P = .01;
      activity limitations: 0.32; 95% CI, 0.01-0.63; P = .04; and the role-emotional
      impairment and social function: 0.96; 95% CI, 0.03-1.90; P = .04). Adverse
      effects of escitalopram (P < .05 vs placebo) were fatigue or somnolence (35
      patients [41.1%]), sleep disturbance (12 [14.1%]), and urinary symptoms (8
      [9.4%]). CONCLUSIONS: Older adults with GAD randomized to escitalopram had a
      higher cumulative response rate for improvement vs placebo over 12 weeks;
      however, response rates were not significantly different using an intention-to
      treat analysis. Further study is required to assess efficacy and safety over
      longer treatment durations. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00105586.

PMID- 19155458
TI  - Does this patient have a pleural effusion?
AB  - CONTEXT: Pleural effusion is a common finding among patients presenting with
      respiratory symptoms. The value of the bedside examination to detect pleural
      effusion is unclear. OBJECTIVE: To systematically review the evidence regarding
      the accuracy of the physical examination in assessing the probability of a
      pleural effusion. DATA SOURCES: We searched MEDLINE (1950-October 2008) and
      EMBASE (1980-October 2008) using Ovid to identify English-language studies
      conducted in a clinical setting. Additional studies were identified by searching
      the bibliographies of retrieved articles and contacting experts in the field.
      STUDY SELECTION: We included prospective studies of diagnostic accuracy that
      compared at least 1 physical examination maneuver with radiographic confirmation
      of pleural effusion. DATA EXTRACTION: Three authors independently appraised study
      quality and extracted relevant data. Data regarding participant recruitment,
      reference standard, diagnostic test(s), and test accuracy were extracted.
      Disagreements were resolved by consensus. DATA SYNTHESIS: We identified 310
      unique citations, but only 5 prospectively conducted studies met inclusion
      criteria (N = 934 patients). A random-effects model was used for quantitative
      synthesis. Of the 8 physical examination maneuvers evaluated in the included
      studies (conventional percussion, auscultatory percussion, breath sounds, chest
      expansion, tactile vocal fremitus, vocal resonance, crackles, and pleural
      friction rub), dullness to conventional percussion was most accurate for
      diagnosing pleural effusion (summary positive likelihood ratio, 8.7; 95%
      confidence interval, 2.2-33.8), while the absence of reduced tactile vocal
      fremitus made pleural effusion less likely (negative likelihood ratio, 0.21; 95%
      confidence interval, 0.12-0.37). CONCLUSIONS: Based on the limited number of
      studies, dullness to percussion and tactile fremitus are the most useful findings
      for pleural effusion. Dull chest percussion makes the probability of a pleural
      effusion much more likely but requires a chest radiograph to confirm the
      diagnosis. When the pretest probability of pleural effusion is low, the absence
      of reduced tactile vocal fremitus makes pleural effusion less likely so that a
      chest radiograph might not be necessary depending on the overall clinical
      situation.

PMID- 19155459
TI  - Nutritively sweetened beverage consumption and obesity: the need for solid
      evidence on a fluid issue.

PMID- 19155460
TI  - Consumer-driven health care may not be what patients need--caveat emptor.

PMID- 19155461
TI  - Contracting schizophrenia: lessons from the influenza epidemic of 1918-1919.

PMID- 19155462
TI  - Ready-to-use therapeutic food for the prevention of wasting in children.

PMID- 19155463
TI  - JAMA patient page. Pleural effusion.

PMID- 19155464
TI  - The origin of the "one cell-one antibody" rule.

PMID- 19155465
TI  - Pillars article: antibody production by single cells. 1958. Nature 181: 1419
      1420.

PMID- 19155466
TI  - Cutting edge: histamine receptor H4 activation positively regulates in vivo IL-4
      and IFN-gamma production by invariant NKT cells.
AB  - Histamine (HA) is a biogenic amine with multiple activities in the immune system.
      In this study we demonstrate that histamine-free histidine decarboxylase
      deficient (HDC(-/-)) mice present a numerical and functional deficit in invariant
      NK T (iNKT) cells as evidenced by a drastic decrease of IL-4 and IFN-gamma
      production. This deficiency was established both by measuring cytokine levels in
      the serum and intracellularly among gated iNKT cells. It resulted from the lack
      of HA, because a single injection of this amine into HDC(-/-) mice sufficed to
      restore normal IL-4 and IFN-gamma production. HA-induced functional recovery was
      mediated mainly through the H4 histamine receptor (H4R), as assessed by its
      abrogation after a single injection of a selective H4R antagonist and the
      demonstration of a similar iNKT cell deficit in H4R(-/-) mice. Our findings
      identify a novel function of HA through its H4R and suggest that it might become
      instrumental in modulating iNKT cell functions.

PMID- 19155467
TI  - Cutting edge: an IL-17F-CreEYFP reporter mouse allows fate mapping of Th17 cells.
AB  - The need for reporter lines able to faithfully track Th17 cells in vivo has
      become an issue of exceptional importance. To address this, we generated a mouse
      strain in which Cre recombinase is expressed from the IL-17F promoter. Crossing
      the IL-17F-Cre allele to a conditional enhanced yellow fluorescent protein (EYFP)
      reporter mouse yielded the IL-17F-Cre(EYFP) strain, in which IL-17F expression is
      twinned with EYFP in live IL-17F-expressing cells. Although we demonstrate that
      IL-17F expression is restricted to CD4(+) T cells during experimental autoimmune
      encephalomyelitis, IL-17F-Cre(EYFP) CD8 T cells robustly expressed IL-17F in
      response to TGF-beta, IL-6, and IL-23. Fate mapping of IL-17F-expressing reporter
      T cells revealed a significant down-regulation of Th17 cytokines after
      homeostatic expansion in RAG1-deficient animals. Despite this loss of effector
      phenotype, committed Th17 cells were resistant to Foxp3 expression in vitro or in
      vivo. Thus, the IL-17F-Cre strain furthers our understanding of Th17 biology.

PMID- 19155468
TI  - Cutting edge: permissive MHC class II allele changes the pattern of antitumor
      immune response resulting in failure of tumor rejection.
AB  - We studied the growth of transgenic adenocarcinoma of mouse prostate (TRAMP)-C1
      tumor cells expressing human prostate-specific Ag (PSA) in HLA-DRB1*1501 (DR2b)
      transgenic mice. TRAMP-PSA tumors were frequently rejected by HLA-DR2b(-) mice
      but had increased incidence in HLA-DR2b(+) littermates. The levels of PSA
      specific CD8 T cell responses were significantly higher in the HLA-DR2b(-) mice
      that rejected TRAMP-PSA tumors compared with HLA-DR2b(+) tumor-bearing
      littermates. In contrast, Ab responses to PSA were strong in HLA-DR2b(+) mice
      bearing TRAMP-PSA tumors and were virtually undetectable in HLA-DR2b(-)
      littermates. The analysis of CD4 T cell responses to PSA revealed the presence of
      several CD4 T cell epitopes in HLA-DR2b(+) mice but failed to identify strong I
      A(b)-restricted epitopes in HLA-DR2b(-) mice. Our data demonstrate that the
      expression of a permissive HLA class II allele can change the pattern of the
      immune response to a tumor Ag, resulting in the failure of tumor rejection.

PMID- 19155469
TI  - Autoimmunity in dry eye is due to resistance of Th17 to Treg suppression.
AB  - Dry eye disease (DED), an inflammatory autoimmune disorder affecting the ocular
      surface, degrades visual performance and the quality of life of >10 million
      people in the United States alone. The primary limitation in the effective
      treatment of DED is an incomplete understanding of its specific cellular and
      molecular pathogenic elements. Using a validated mouse model of DED, herein we
      functionally characterize the different T cell subsets, including regulatory T
      cells (Tregs) and pathogenic effector T cells, and determine their contribution
      to the pathogenesis of DED. Our data demonstrate the presence of dysfunctional
      Tregs and the resistance of pathogenic T cells, particularly Th17 cells, to Treg
      suppression in DED. In addition, we clearly show that in vivo blockade of IL-17
      significantly reduces the severity and progression of disease, which is
      paralleled by a reduction in the expansion of Th17 cells and restoration of Treg
      function. Our findings elucidate involvement of a previously unknown pathogenic T
      cell subset (Th17) in DED that is associated specifically with Treg dysfunction
      and disease pathogenesis and suggest a new target for dry eye therapy.

PMID- 19155470
TI  - ISCOMATRIX adjuvant induces efficient cross-presentation of tumor antigen by
      dendritic cells via rapid cytosolic antigen delivery and processing via
      tripeptidyl peptidase II.
AB  - Cancer vaccines aim to induce antitumor CTL responses, which require cross
      presentation of tumor Ag to CTLs by dendritic cells (DCs). Adjuvants that
      facilitate cross-presentation of vaccine Ag are therefore key for inducing
      antitumor immunity. We previously reported that human DCs could not efficiently
      cross-present the full-length cancer/testis Ag NY-ESO-1 to CTL unless formulated
      as either an immune complex (NY-ESO-1/IC) or with ISCOMATRIX adjuvant. We now
      demonstrate that NY-ESO-1/ICs induce cross-presentation of HLA-A2- and HLA-Cw3
      restricted epitopes via a proteasome-dependent pathway. In contrast, cross
      presentation of NY-ESO-1/ISCOMATRIX vaccine was proteasome independent and
      required the cytosolic protease tripeptidyl peptidase II. Trafficking studies
      revealed that uptake of ICs and ISCOMATRIX vaccine by DCs occurred via
      endocytosis with delivery to lysosomes. Interestingly, ICs were retained in
      lysosomes, whereas ISCOMATRIX adjuvant induced rapid Ag translocation into the
      cytosol. Ag translocation was dependent on endosomal acidification and IL-4
      driven differentiation of monocytes into DCs. This study demonstrates that Ag
      formulation determines Ag processing and supports a role for tripeptidyl
      peptidase II in cross-presentation of CTL epitopes restricted to diverse HLA
      alleles.

PMID- 19155471
TI  - Targeting antigen to MHC class II molecules promotes efficient cross-presentation
      and enhances immunotherapy.
AB  - An efficient pathway of cross-presentation common to a range of dendritic cell
      (DC) populations was identified by targeting Ag to MHC class II molecules. This
      finding was achieved by conjugating Ag to M1, which is a modified version of the
      superantigen streptococcal mitogenic exotoxin Z-2 that binds to MHC class II
      molecules but cannot directly stimulate T cells. M1 conjugates were efficiently
      presented to CD4(+) and CD8(+) T cells by bone marrow-derived DC and Langerhans
      cells in vitro. Whereas nonconjugated Ag was preferentially cross-presented by
      splenic CD8alpha(+) DC in vivo, M1-conjugated Ag was cross-presented by all
      dendritic subtypes assessed. Potent effector T cell responses with antitumor
      activity were elicited when M1 conjugates were injected together with an
      adjuvant. This method of Ag delivery has significant potential in therapeutic
      applications.

PMID- 19155472
TI  - Chemokine-enhanced chemotaxis of lymphangioleiomyomatosis cells with mutations in
      the tumor suppressor TSC2 gene.
AB  - Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction caused
      by LAM cells (smooth-muscle-like cells) that have mutations in the tumor
      suppressor genes tuberous sclerosis complex (TSC) 1 or 2 and have the capacity to
      metastasize. Since chemokines and their receptors function in chemotaxis of
      metastatic cells, we hypothesized that LAM cells may be recruited by chemokine(s)
      in the lung. Quantification of 25 chemokines in bronchoalveolar lavage fluid from
      LAM patients and healthy volunteers revealed that concentrations of CCL2, CXCL1,
      and CXCL5 were significantly higher in samples from LAM patients than those from
      healthy volunteers. In vitro, CCL2 or MCP-1 induced selective migration of cells,
      showing loss of heterozygosity of TSC2 from a heterogeneous population of cells
      grown from explanted LAM lungs. Additionally, the frequencies of single
      nucleotide polymorphisms in the CCL2 gene promoter region differed significantly
      in LAM patients and healthy volunteers (p = 0.018), and one polymorphism was
      associated significantly more frequently with the decline of lung function. The
      presence (i.e., potential functionality) of chemokine receptors was evaluated
      using immunohistochemistry in lung sections from 30 LAM patients. Expression of
      chemokines and these receptors varied among LAM patients and differed from that
      seen in some cancers (e.g., breast cancer and melanoma cells). These observations
      are consistent with the notion that chemokines such as CCL2 may serve to
      determine mobility and specify the site of metastasis of the LAM cell.

PMID- 19155474
TI  - CXC chemokine ligand 12 promotes CCR7-dependent naive T cell trafficking to lymph
      nodes and Peyer's patches.
AB  - A number of chemokines, including CCL21, CCL19, CXCL12, and CXCL13, are
      coexpressed on the lumen or basal lamina of high endothelial venules (HEVs) in
      lymph nodes (LNs) and Peyer's patches (PPs), consistent with the idea that they
      might cooperate to regulate lymphocyte trafficking into these lymphoid tissues.
      In this study we report that CXCL12, acting through its receptor, CXCR4,
      cooperates with CCR7 ligands to promote T cell trafficking across HEVs. CXCL12
      enhanced the CCR7-induced chemotaxis of wild-type but not CXCR4-deficient T cells
      in vitro at suboptimal concentrations of a CCR7 ligand, but without affecting the
      expression level or ligand-binding ability of CCR7. Real-time chemotaxis analysis
      showed that CXCL12 substantially shortened the lag time before cell migration
      began in vitro, but not the migration speed of T cells responding to suboptimal
      CCR7 ligand concentrations. In addition, CXCL12 augmented the CCR7 ligand-driven
      ERK phosphorylation and actin polymerization in T cells under the same
      conditions. In adoptive transfer experiments, CXCL12 promoted naive T cell
      trafficking to LNs and PPs in wild-type but not CCR7 ligand-deficient plt/plt
      recipient mice; this increased T cell trafficking was associated with enhanced
      binding of the T cells to HEVs and their subsequent migration into the LN
      parenchyma. Thus, CXCL12 synergizes with CCR7 ligands to promote T cell migration
      by sensitizing T cells through CXCR4, thus enabling them to respond to lower
      concentrations of CCR7 ligands. Such concerted action of chemokines provides an
      additional, previously unknown mechanism for efficient lymphocyte trafficking
      across HEVs into LNs and PPs.

PMID- 19155473
TI  - A new triggering receptor expressed on myeloid cells (Trem) family member, Trem
      like 4, binds to dead cells and is a DNAX activation protein 12-linked marker for
      subsets of mouse macrophages and dendritic cells.
AB  - Dendritic cells (DCs) are professional APCs that can control immune responses
      against self and altered self, typically foreign, determinants. DCs can be
      divided into several subsets, including CD8alpha(+) and CD8alpha(-) DCs. These
      subsets possess specific functions. For example, mouse splenic CD8alpha(+), but
      not CD8alpha(-) DCs selectively take up dying cells and cross-present cell
      associated Ags to naive T cells. In this study, we identified genes that were
      more expressed in CD8alpha(+) than CD8alpha(-) DCs by microarray analysis. Only
      one of these genes, when the extracellular domains were linked to human IgG Fc
      domain, could bind to late apoptotic or necrotic cells. This gene was a new
      member of the triggering receptor expressed on myeloid cells (Trem) family, Trem
      like 4 (Treml4). Treml4 mRNA and protein, the latter detected with a new mAb,
      were predominantly expressed in spleen. Treml4, like other Trem family members,
      could associate with the adaptor molecule DNAX activation protein 12 kDa, but
      neither DNAX activation protein 10 kDa nor FcRgamma. Consistent with the
      microarray data, we confirmed that Treml4 protein was more expressed on
      CD8alpha(+) than CD8alpha(-) DCs, and we also found that Treml4 was expressed at
      high levels on splenic macrophages in spleen, particularly red pulp and marginal
      metallophilic macrophages. In addition, Treml4 expression on DCs was not changed
      after maturation induced by TLR ligands. Thus, Treml4 is a new Trem family
      molecule that is abundantly expressed on CD8alpha(+) DCs and subsets of splenic
      resident macrophages, and can recognize dead cells by different types of
      phagocytes in spleen.

PMID- 19155476
TI  - Scrapie pathogenesis: the role of complement C1q in scrapie agent uptake by
      conventional dendritic cells.
AB  - Mice lacking complement components show delayed development of prion disease
      following peripheral inoculation. The delay could relate to reduced scrapie prion
      protein (PrP(Sc)) accumulation on follicular dendritic cells (DCs). However
      conventional DCs (cDCs) play a crucial role in the early pathogenesis of prion
      diseases and complement deficiency could result in decreased PrP(Sc) uptake by
      cDCs in the periphery. To explore this possibility, we cultured murine splenic or
      gut-associated lymph node cDCs with scrapie-infected whole brain homogenate in
      the presence or absence of complement. Uptake decreased significantly if the
      serum in the cultures was heat-inactivated. Because heat inactivation primarily
      denatures C1q, we used serum from C1q(-/-) mice and showed that PrP(Sc) uptake
      was markedly decreased. PrP(Sc) internalization was saturable and temperature
      dependent, suggesting receptor-mediated uptake. Furthermore, uptake
      characteristics differed from fluid-phase endocytosis. Immunofluorescence showed
      colocalization of C1q and PrP(Sc), suggesting interaction between these
      molecules. We evaluated the expression of several complement receptors on cDCs
      and confirmed that cDCs that take up PrP(Sc) express one of the C1q receptors,
      calreticulin. Our results show that C1q participates in PrP(Sc) uptake by cDCs,
      revealing a critical role for cDCs in initial prion capture, an event that takes
      place before the PrP(Sc) accumulation within the follicular DC network.

PMID- 19155475
TI  - Differentiated human alveolar type II cells secrete antiviral IL-29 (IFN-lambda
      1) in response to influenza A infection.
AB  - Alveolar type II epithelial cells (ATIIs) are one of the primary targets for
      influenza A pneumonia. The lack of a culture system for maintaining
      differentiated ATIIs hinders our understanding of pulmonary innate immunity
      during viral infection. We studied influenza A virus (IAV)-induced innate immune
      responses in differentiated primary human ATIIs and alveolar macrophages (AMs).
      Our results indicate that ATIIs, but not AMs, support productive IAV infection.
      Viral infection elicited strong inflammatory chemokine and cytokine responses in
      ATIIs, including secretion of IL-8, IL-6, MCP-1, RANTES, and MIP-1beta, but not
      TNF-alpha, whereas AMs secreted TNF-alpha as well as other cytokines in response
      to infection. Wild-type virus A/PR/8/34 induced a greater cytokine response than
      reassortant PR/8 virus, A/Phil/82, despite similar levels of replication. IAV
      infection increased mRNA expression of IFN genes IFN-beta, IL-29 (IFN-lambda1),
      and IL-28A (IFN-lambda2). The major IFN protein secreted by type II cells was IL
      29 and ATIIs appear to be a major resource for production of IL-29.
      Administration of IL-29 and IFN-beta before infection significantly reduced the
      release of infectious viral particles and CXC and CC chemokines. IL-29 treatment
      of type II cells induced mRNA expression of antiviral genes MX1, OAS, and ISG56
      but not IFN-beta. IL-29 induced a dose-dependent decrease of viral nucleoprotein
      and an increase of antiviral genes but not IFN-beta. These results suggest that
      IL-29 exerts IFN-beta-independent protection in type II cells through direct
      activation of antiviral genes during IAV infection.

PMID- 19155477
TI  - Memory alloreactive B cells and alloantibodies prevent anti-CD154-mediated
      allograft acceptance.
AB  - The impact of memory B cells and alloantibodies on the ability to induce
      transplantation tolerance has not been elucidated. We have developed a murine
      heart transplant model that isolates the contributions of functional memory B
      cells from memory T cells in allograft rejection. Memory 3-83 B cells with dual
      specificity for H-2K(k) and H-2K(b) were generated in 3-83 Igi BCR knockin
      (BALB/c background) mice by the transplantation of C3H (H-2K(k)) hearts in the
      absence of immunosuppression. To test the effect of functional memory 3-83 B
      cells, C3H-primed 3-83 Igi recipients were challenged with C57BL/6 hearts (H
      2K(b)) at 60-90 days post-C3H heart transplant and treated with anti-CD154 mAbs.
      Despite immunosuppression, the C57BL/6 hearts were acutely rejected within 10-13
      days and graft rejection was associated with increased frequencies of C57BL/6
      specific IFN-gamma-producing T cells. Histology revealed significant numbers of
      infiltrating T cells, consistent with acute T cell-mediated rejection. The
      resistance to tolerance induction was dependent on the synergistic effects of
      memory 3-83 B cells and alloantibodies, whereas memory T cells are not necessary.
      We conclude that the combined effects of functional memory B cells and
      alloantibodies prevent anti-CD154-mediated graft acceptance by facilitating the
      CD40-CD154-independent activation of alloreactive T cells. This study provides
      insight into the potential ability of memory B cells and alloantibodies to
      prevent anti-CD154-mediated graft acceptance.

PMID- 19155478
TI  - MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7
      H1 expression in cholangiocytes.
AB  - Biliary epithelial cells (cholangiocytes) respond to proinflammatory cytokines
      such as IFN-gamma and actively participate in the regulation of biliary
      inflammatory response in the liver. B7-H1 (also known as CD274 or PD-L1) is a
      member of the B7 costimulatory molecules and plays a critical immunoregulatory
      role in cell-mediated immune responses. In this study, we show that resting human
      cholangiocytes in culture express B7-H1 mRNA, but not B7-H1 protein. IFN-gamma
      induces B7-H1 protein expression and alters the microRNA (miRNA) expression
      profile in cholangiocytes. Of those IFN-gamma-down-regulated miRNAs, we
      identified microRNA-513 (miR-513) with complementarity to the 3'-untranslated
      region of B7-H1 mRNA. Targeting of the B7-H1 3'-untranslated region by miR-513
      results in translational repression. Transfection of cholangiocytes with an
      antisense oligonucleotide to miR-513 induces B7-H1 protein expression.
      Additionally, transfection of miR-513 precursor decreases IFN-gamma-induced B7-H1
      protein expression and consequently influences B7-H1-associated apoptotic cell
      death in cocultured Jurkat cells. Thus, miR-513 regulates B7-H1 translation and
      is involved in IFN-gamma-induced B7-H1 expression in human cholangiocytes,
      suggesting a role for miRNA-mediated gene silencing in the regulation of
      cholangiocyte response to IFN-gamma.

PMID- 19155479
TI  - Protein tyrosine phosphatases regulate asthma development in a murine asthma
      model.
AB  - Allergic asthma is a chronic inflammatory disease characterized by Th2-type
      inflammation. Although the cellular interactions are now well studied, the
      intracellular signaling involved in asthma development is still a developing
      field. Protein tyrosine kinases are one focus of such research and their
      inhibition shows improvement of asthmatic features. Interestingly, very little
      attention was given to protein tyrosine phosphatases (PTPs), the counterparts to
      protein tyrosine kinases, in the development of asthma. Previous studies from our
      laboratory showed that pharmacological inhibition of PTPs induced a transient Th1
      response in the spleen. Therefore, we hypothesized that modulation of PTPs could
      influence asthma development. To assess PTP functions, we used the PTP inhibitor
      bis-peroxovanadium bpV(phen) in a murine model of asthma during either allergen
      sensitization or challenge. Inhibition of PTPs during allergen sensitization
      resulted in the reduction of key features of allergic asthma: serum IgE levels,
      lung tissue inflammation, eosinophilia, and airway hyperresponsiveness. Of utmost
      interest, PTP inhibition at allergen challenge resulted in a very similar
      improvement of asthmatic features. Of further importance, we observed that
      bpV(phen) treatment modulated cytokine expression in the spleen and, more
      specifically, favored Th1 cytokines while inhibiting Th2 cytokines. Collectively,
      we show for the first time that intact activity of PTPs is required for a
      complete induction of asthma in a mouse model. This clearly suggests that PTPs
      have a pivotal regulatory role in the development of asthmatic diseases, which
      opens the possibility of new therapeutic avenues.

PMID- 19155480
TI  - Affinity-based selection of regulatory T cells occurs independent of agonist
      mediated induction of Foxp3 expression.
AB  - Natural regulatory T (nT(reg)) cells recognize self-peptides with high affinity,
      yet the understanding of how affinity influences their selection in the thymus is
      incomplete. We use altered peptide ligands in transgenic mice and in organ
      culture to create thymic environments spanning a broad range of ligand affinity.
      We demonstrate that the nT(reg) TCR repertoire is shaped by affinity-based
      selection, similar to conventional T cells. The effect of each ligand on the two
      populations is distinct, consistent with early nT(reg) cell lineage
      specification. Foxp3 expression is an independent process that does not rely on
      "high affinity" binding per se, but requires a high-potency agonistic interaction
      for its induction. The timing of ligand exposure, TGFbeta signaling, and the
      organization of the thymic architecture are also important. The development of
      nT(reg) cells is therefore a multistep process in which ligand affinity, potency,
      and timing of presentation all play a role in determining cell fate.

PMID- 19155481
TI  - IL-12 enhances CTL synapse formation and induces self-reactivity.
AB  - Immunological synapse formation between T cells and target cells can affect the
      functional outcome of TCR ligation by a given MHC-peptide complex. Although
      synapse formation is usually induced by TCR signaling, it is not clear whether
      other factors can affect the efficiency of synapse formation. Here, we tested
      whether cytokines could influence synapse formation between murine CTLs and
      target cells. We found that IL-12 enhanced synapse formation, whereas TGFbeta
      decreased synapse formation. The enhanced synapse formation induced by IL-12
      appeared to be functional, given that IL-12-treated cells could respond to weak
      peptides, including self-peptides, to which the T cells were normally
      unresponsive. These responses correlated with expression of functionally higher
      avidity LFA-1 on IL-12-treated CTLs. These findings have implications for the
      function of IL-12 in T cell-mediated autoimmunity.

PMID- 19155482
TI  - The epigenetic profile of Ig genes is dynamically regulated during B cell
      differentiation and is modulated by pre-B cell receptor signaling.
AB  - Ag receptor loci poised for V(D)J rearrangement undergo germline transcription
      (GT) of unrearranged genes, and the accessible gene segments are associated with
      posttranslational modifications (PTM) on histones. In this study, we performed a
      comprehensive analysis of the dynamic changes of four PTM throughout B and T cell
      differentiation in freshly isolated ex vivo cells. Methylation of lysines 4 and
      79 of histone H3, and acetylation of H3, demonstrated stage and lineage
      specificity, and were most pronounced at the J segments of loci poised for, or
      undergoing, rearrangement, except for dimethylation of H3K4, which was more
      equally distributed on V, D, and J genes. Focusing on the IgL loci, we
      demonstrated there are no active PTM in the absence of pre-BCR signaling. The
      kappa locus GT and PTM on Jkappa genes are rapidly induced following pre-BCR
      signaling in large pre-B cells. In contrast, the lambda locus shows greatly
      delayed onset of GT and PTM, which do not reach high levels until the immature B
      cell compartment, the stage at which receptor editing is initiated. Analysis of
      MiEkappa(-/-) mice shows that this enhancer plays a key role in inducing not only
      GT, but PTM. Using an inducible pre-B cell line, we demonstrate that active PTM
      on Jkappa genes occur after GT is initiated, indicating that histone PTM do not
      make the Jkappa region accessible, but conversely, GT may play a role in adding
      PTM. Our data indicate that the epigenetic profile of IgL genes is dramatically
      modulated by pre-BCR signaling and B cell differentiation status.

PMID- 19155483
TI  - The adaptor molecule signaling lymphocytic activation molecule-associated protein
      (SAP) regulates IFN-gamma and IL-4 production in V alpha 14 transgenic NKT cells
      via effects on GATA-3 and T-bet expression.
AB  - NKT cells comprise a rare regulatory T cell population of limited TCR diversity,
      with most cells using a Valpha14 Jalpha18 TCR. These cells exhibit a critical
      dependence on the signaling adapter molecule, signaling lymphocytic activation
      molecule-associated protein (SAP), for their ontogeny, an aspect not seen in
      conventional alphabeta T cells. Prior studies demonstrate that SAP enhances TCR
      induced activation of NF-kappaB in CD4(+) T cells. Because NF-kappaB is required
      for NKT cell development, SAP might promote the ontogeny of this lineage by
      signaling to NF-kappaB. In this study, we demonstrate that forced expression of
      the NF-kappaB target gene, Bcl-x(L), or inhibitory NF-kappaB kinase beta, a
      catalytic subunit of the IkappaB kinase complex essential for NF-kappaB
      activation, fails to restore NKT cell development in sap(-/-) mice, suggesting
      that SAP mediates NKT cell development independently of NF-kappaB. To examine the
      role of SAP in NKT cell function, we generated NKT cells in sap(-/-) mice by
      expressing a transgene encoding the Valpha14 Jalpha18 component of the invariant
      TCR. These cells bound alpha-galactosylceramide-loaded CD1d tetramers, but
      exhibited a very immature CD24(+)NK1.1(-) phenotype. Although sap(-/-) tetramer
      reactive cells proliferated in response to TCR activation, they did not produce
      appreciable levels of IL-4 or IFN-gamma. The reduction in cytokine production
      correlated with the near absence of GATA-3 and T-bet, key transcription factors
      regulating cytokine expression and maturation of NKT cells. Ectopic expression of
      GATA-3 partially restored IL-4 production by the NKT cells. Collectively, these
      data suggest that by promoting GATA-3 and T-bet expression, SAP exerts control
      over NKT cell development and mature NKT cell cytokine production.

PMID- 19155484
TI  - Tim-1 signaling substitutes for conventional signal 1 and requires costimulation
      to induce T cell proliferation.
AB  - Differentiation and clonal expansion of Ag-activated naive T cells play a pivotal
      role in the adaptive immune response. T cell Ig mucin (Tim) proteins influence
      the activation and differentiation of T cells. Tim-3 and Tim-2 clearly regulate
      Th1 and Th2 responses, respectively, but the precise influence of Tim-1 on T cell
      activation remains to be determined. We now show that Tim-1 stimulation in vivo
      and in vitro induces polyclonal activation of T cells despite absence of a
      conventional TCR-dependent signal 1. In this model, Tim-1-induced proliferation
      is dependent on strong signal 2 costimulation provided by mature dendritic cells.
      Ligation of Tim-1 upon CD4(+) T cells with an agonist anti-Tim-1 mAb elicits a
      rise in free cytosolic calcium, calcineurin-dependent nuclear translocation of NF
      AT, and transcription of IL-2. Because Tim-4, the Tim-1 ligand, is expressed by
      mature dendritic cells, we propose that interaction between Tim-1(+) T cells and
      Tim-4(+) dendritic cells might ensure optimal stimulation of T cells, when TCR
      derived signals originating within an inflamed environment are weak or waning.

PMID- 19155485
TI  - TLR9-dependent activation of dendritic cells by DNA from Leishmania major favors
      Th1 cell development and the resolution of lesions.
AB  - In its vertebrate host, Leishmania encounters cells that express TLRs. Using
      genetically resistant C57BL/6 mice deficient in either TLR2, 4, or 9, we show in
      this study that only TLR9-deficient mice are more susceptible to infection with
      Leishmania major. TLR9-deficient mice resolved their lesions and controlled
      parasites growth with much lower efficiency than wild-type C57BL/6 mice. The
      absence of TLR9 also transiently inhibited the development of curative Th1
      response. In an attempt to analyze the possible basis for such aberrant response
      in TLR9(-/-) mice, we have studied the importance of TLR9 for the activation of
      dendritic cells (DCs) by L. major. Results show that DCs in the draining lymph
      nodes are activated following infection with L. major. Furthermore, bone marrow
      derived DCs as well as DCs freshly isolated from the spleen of C57BL/6 mice can
      be activated by either heat-killed or live L. major in vitro. In sharp contrast,
      L. major failed to activate DCs from TLR9(-/-) mice. Noteworthily, activation of
      DCs was abolished either following treatment of the parasites with DNase or after
      acidification of the endosomal compartment of DCs by chloroquine, pinpointing the
      DNA of L. major as the possible ligand of TLR9 leading to the activation of DCs.
      Results showed that DNA purified from L. major was indeed capable of activating
      DCs in a strictly TLR9-dependent manner. Moreover we showed that the L. major DNA
      induced TLR9 signaling in DCs condition these cells to promote IFN-gamma
      production by CD4(+) T cells.

PMID- 19155486
TI  - Macrophages activated by C-reactive protein through Fc gamma RI transfer
      suppression of immune thrombocytopenia.
AB  - C-reactive protein (CRP) is an acute-phase protein with therapeutic activity in
      mouse models of systemic lupus erythematosus and other inflammatory and
      autoimmune diseases. To determine the mechanism by which CRP suppresses immune
      complex disease, an adoptive transfer system was developed in a model of immune
      thrombocytopenic purpura (ITP). Injection of 200 microg of CRP 24 h before
      induction of ITP markedly decreased thrombocytopenia induced by anti-CD41. CRP
      treated splenocytes also provided protection from ITP in adoptive transfer.
      Splenocytes from C57BL/6 mice were treated with 200 microg/ml CRP for 30 min,
      washed, and injected into mice 24 h before induction of ITP. Injection of 10(6)
      CRP-treated splenocytes protected mice from thrombocytopenia, as did i.v. Ig
      treated but not BSA-treated splenocytes. The suppressive cell induced by CRP was
      found to be a macrophage by depletion, enrichment, and the use of purified bone
      marrow-derived macrophages. The induction of protection by CRP-treated cells was
      dependent on FcRgamma-chain and Syk activation, indicating an activating effect
      of CRP on the donor cell. Suppression of ITP by CRP-treated splenocytes required
      Fc gamma RI on the donor cell and Fc gamma RIIb in the recipient mice. These
      findings suggest that CRP generates suppressive macrophages through Fc gamma RI,
      which then act through an Fc gamma RIIb-dependent pathway in the recipient to
      decrease platelet clearance. These results provide insight into the mechanism of
      CRP regulatory activity in autoimmunity and suggest a potential new therapeutic
      approach to ITP.

PMID- 19155488
TI  - Placental cytokine expression covaries with maternal asthma severity and fetal
      sex.
AB  - In the presence of maternal asthma, we have previously reported reduced placental
      blood flow, decreased cortisol metabolism, and reductions in fetal growth in
      response to maternal asthma and asthma exacerbations. We have proposed that these
      changes in placental function and fetal development may be related to activation
      of proinflammatory pathways in the placenta in response to maternal asthma. In
      the present study, we examined the influence of maternal asthma severity, inhaled
      glucocorticoid treatment, maternal cigarette use, placental macrophage numbers,
      and fetal sex on placental cytokine mRNA expression from a prospective cohort
      study of pregnant women with and without asthma. Placental expression of TNF
      alpha, IL-1beta, IL-6, IL-8, and IL-5 mRNA were all increased significantly in
      placentae of female fetuses whose mothers had mild asthma, but no changes were
      observed in placentae of male fetuses. The proinflammatory cytokines TNF-alpha,
      IL-1beta, and IL-6 were negatively correlated with female cord blood cortisol,
      but there were no such correlations in placentae from males. Multivariate
      analysis indicated the strongest predictor of both cytokine mRNA expression in
      the placenta and birth weight was fetal cortisol but only in females. Placental
      cytokine mRNA levels were not significantly altered by inhaled glucocorticoid
      use, placental macrophage numbers, cigarette use, moderate-severe asthma, or male
      sex. These data suggest that placental basal cytokine mRNA expression is sex
      specifically regulated in pregnancies complicated by asthma, and interestingly
      these changes are more prevalent in mild rather than severe asthma.

PMID- 19155487
TI  - Potential contribution of IL-7 to allergen-induced eosinophilic airway
      inflammation in asthma.
AB  - The primary function of IL-7 is to promote maturation and survival of T cells.
      Through microarray expression analysis, we previously observed that human blood
      eosinophils express mRNA for IL-7R alpha (CD127) and its common gamma chain
      (CD132). The purpose of this study was to determine whether eosinophils have
      functional IL-7 receptors and to assess the potential contribution of IL-7 to
      eosinophilic airway inflammation by evaluating its presence in bronchoalveolar
      lavage (BAL) fluid of subjects with atopic asthma before and after segmental
      bronchoprovocation with allergen. Immunoblot analysis revealed that CD127 is
      present in highly purified human blood eosinophils. Furthermore, eosinophils
      responded to IL-7 with phosphorylation of STAT5, up-regulation of the activation
      marker CD69, and prolonged survival. Neutralization of GM-CSF but not IL-5
      significantly blunted these functional responses, suggesting that IL-7 mediates
      its effects by promoting eosinophil release of autologous GM-CSF. Notably, the
      suppressive effect of anti-GM-CSF on STAT5 phosphorylation occurred within 10 min
      of eosinophil exposure to IL-7. Thus, IL-7 likely activates eosinophil release of
      preformed rather than newly synthesized GM-CSF. The biological relevance of IL-7
      to eosinophilia in vivo was implicated in a study of airway allergen challenge in
      patients with allergic asthma. IL-7 concentrations in BAL fluid increased
      significantly 48 h after segmental allergen challenge and were highly correlated
      with BAL eosinophils (r = 0.7, p < 0.001). In conclusion, the airway response to
      allergen is associated with the generation of IL-7, which may contribute to
      airway inflammation by promoting enhanced eosinophil activation and survival.
      Activation of eosinophils is a novel function for IL-7.

PMID- 19155489
TI  - B7RP-1 blockade ameliorates autoimmunity through regulation of follicular helper
      T cells.
AB  - Autoimmune diseases are marked by the presence of class-switched, high-affinity
      autoantibodies with pathogenic potential. Costimulation plays an important role
      in the activation of T cells and the development of T cell-dependent B cell
      responses. ICOS plays an indispensable role in the development of follicular
      helper T cells (T(FH) cells), which provide cognate help to germinal center (GC)
      B cells. We show that the levels of T(FH) cells and GC B cells in two different
      models of autoimmunity, the New Zealand Black/New Zealand White (NZB/NZW) F(1)
      mouse model of systemic lupus erythematosus and the collagen-induced arthritis
      model of rheumatoid arthritis, are dependent on the maintenance of the ICOS/B7RP
      1 pathway. Treatment with an anti-B7RP-1 Ab ameliorates disease manifestations
      and leads to a decrease in T(FH) cells and GC B cells as well as an overall
      decrease in the frequency of ICOS(+) T cells. Coculture experiments of Ag-primed
      B cells with CXCR5(+) or CXCR5(-) T cells show that blocking B7RP-1 does not
      directly impact the production of IgG by B cells. These findings further support
      the role of ICOS in autoimmunity and suggest that the expansion of the T(FH) cell
      pool is an important mechanism by which ICOS regulates Ab production.

PMID- 19155490
TI  - Endogenously produced IL-4 nonredundantly stimulates CD8+ T cell proliferation.
AB  - T cell proliferation and survival are regulated by the cytokine receptor common
      gamma-chain-associated cytokines IL-2, IL-7, and IL-15, while IL-4, another gamma
      chain-associated cytokine, is thought to primarily affect T cell quality rather
      than quantity. In contrast, our experiments reveal that endogenously produced IL
      4 is a direct, nonredundant, and potent stimulator of CD8(+) T cell proliferation
      in Ag- and pathogen-induced CD8(+) T cell responses. These stimulatory effects of
      IL-4 are observed in both BALB/c and C57BL/6 mice and activate both naive and
      memory/activated phenotype CD8(+) T cells, although the former are stimulated
      less than are the latter. IL-4 effects are IL-7- and IL-15-independent, but MHC
      class I-dependent stimulation appears to be required for the mitogenic effect of
      IL-4 on naive phenotype CD8(+) T cells. Thus, endogenously produced IL-4 is an
      important regulator of quantitative as well as qualitative aspects of T cell
      immunity.

PMID- 19155491
TI  - Increased IL-15 production is associated with higher susceptibility of memory CD4
      T cells to simian immunodeficiency virus during acute infection.
AB  - Acute SIV infection is characterized by explosive infection of memory CD4 T cells
      in peripheral and mucosal tissues. Interestingly, relatively few memory CD4 T
      cells are infected until as late as days 7-8 after challenge. However, by day 10
      postinfection, most of the memory CD4 T cells are infected and carry viral DNA.
      The rapidity with which infection expands within 2-3 days to encompass virtually
      the entire memory CD4 T cell compartment suggests significant alterations in the
      susceptibility of memory CD4 T cells to infection during this period. The
      mechanism(s) underlying this increased permissiveness to infection is not known.
      In this study, we show that IL-15 secretion significantly correlates with the up
      regulated expression of CD4 on memory CD4 T cells that is associated with
      increased permissiveness to SIV infection. Activation and proliferation of memory
      CD8, but not memory CD4 T cells, preceded the amplification of viral infection.
      Although memory CD4 T cells did not express normal activation markers, they
      displayed a significant up-regulation in the density of CD4 but not CCR5
      expression between days 7 and 10 postinfection that correlated with increased
      plasma IL-15 levels and infection in these cells. Culture of purified CD4 T cells
      with IL-15 and/or SIV was associated with a significant increase in the
      expression of CD4 and infection of these sorted cells. Our results demonstrate
      that IL-15 contributes to the increased susceptibility of memory CD4 T cells to
      SIV during the early phase of acute SIV infection.

PMID- 19155492
TI  - Heat shock protein 70, released from heat-stressed tumor cells, initiates
      antitumor immunity by inducing tumor cell chemokine production and activating
      dendritic cells via TLR4 pathway.
AB  - Extracellular heat shock proteins (HSP) can activate dendritic cells (DC) and
      monocytes/macrophages, and HSP derived from tumor cells have been regarded as
      potent adjuvant facilitating presentation of tumor Ags and induction of antitumor
      immunity. However, the roles and the underlying mechanisms of releasable HSP in
      the induction of antitumor immunity have not been fully elucidated. In this
      study, we report that heat stress can induce the release of various HSP from
      tumor cells, which, in turn, activate tumor cells to produce chemokines for
      chemoattraction of DC and T cells via TLR4 signaling pathway. In vivo, we find
      that the infiltration and function of DC and T cells within tumor after local
      hyperthermia are increased significantly. We also provide evidence that HSP70
      proteins released by tumor cells and TLR4 expressed by tumor cells/DC are
      essential for the chemoattraction of DC/T cells and for the subsequent induction
      of tumor-specific antitumor immunity. Therefore, our study suggests that heat
      stress-induced releasable HSP70 proteins from tumor cells play important roles in
      the initiation of antitumor immunity by inducing tumor cell production of
      chemokines and by activating the chemoattracted DC via TLR4 pathway.

PMID- 19155493
TI  - Distinct and overlapping patterns of cytokine regulation of thymic and bone
      marrow-derived NK cell development.
AB  - Although bone marrow (BM) represents the main site for postnatal NK cell
      development, recently a distinct thymic-dependent NK cell pathway was identified.
      These studies were designed to investigate the role of cytokines in regulation of
      thymic NK cells and to compare with established regulatory pathways of BM
      dependent NK cell compartment. The common cytokine receptor gamma-chain (Il2rg)
      essential for IL-15-induced signaling, and FMS-like tyrosine kinase 3 (FLT3)
      receptor ligand (Flt3l) were previously identified as important regulatory
      pathways of the BM NK cell compartment based on lack of function studies in mice,
      however their complementary action remains unknown. By investigating mice double
      deficient in Il2rg and Flt3l (Flt3l(-/-) Il2rg(-/-)), we demonstrate that FLT3L
      is important for IL2Rg-independent maintenance of both immature BM as well as
      peripheral NK cells. In contrast to IL-7, which is dispensable for BM but
      important for thymic NK cells, IL-15 has a direct and important role in both
      thymic and BM NK cell compartments. Although thymic NK cells were not affected in
      Flt3l(-/-) mice, Flt3l(-/-)Il2rg(-/-) mice lacked detectable thymic NK cells,
      suggesting that FLT3L is also important for IL-2Rg-independent maintenance of
      thymic NK cells. Thus, IL-2Rg cytokines and FLT3L play complementary roles and
      are indispensable for homeostasis of both BM and thymic dependent NK cell
      development, suggesting that the cytokine pathways crucial for these two distinct
      NK cell pathways are largely overlapping.

PMID- 19155495
TI  - OX40-enhanced tumor rejection and effector T cell differentiation decreases with
      age.
AB  - OX40 agonists have potent immunotherapeutic effects against a variety of murine
      tumors, yet it is unclear the role that age-related immune senescence plays on
      their efficacy. We found that middle-aged and elderly tumor-bearing mice (12 and
      20 mo old, respectively) treated with anti-OX40 were less responsive compared
      with young mice 6 mo or less of age. Decreased tumor-free survival was observed
      in both male and female mice, and was not due to changes in the surface
      expression of OX40 on T cells in older animals. Enumeration of cytokine-producing
      effector T cells in tumor-bearing mice revealed a significant decline in these
      cells in the older mice treated with anti-OX40 compared with their younger
      counterparts. The decrease of this critical T cell population in middle-aged mice
      was not a result of inherent T cell deficiencies, but was revealed to be T cell
      extrinsic. Finally, combining IL-12, an innate cytokine, with anti-OX40 boosted
      levels of differentiated effector T cells in the older anti-OX40-treated mice and
      partially restored the defective antitumor responses in the middle-aged mice. Our
      data show that the anti-OX40-enhancement of tumor immunity and effector T cell
      numbers is decreased in middle-aged mice and was partially reversed by
      coadministration of the proinflammatory cytokine IL-12.

PMID- 19155494
TI  - Human circulating CD4+CD25highFoxp3+ regulatory T cells kill autologous CD8+ but
      not CD4+ responder cells by Fas-mediated apoptosis.
AB  - Mechanisms utilized by human regulatory T cells (Treg) for elimination of
      effector cells may vary. We investigated the possibility that the mechanism of
      Treg suppression depends on Fas/FasL-mediated apoptosis of responder cells (RC).
      CD4(+)CD25(high)Foxp3(+) Treg and autologous CD4(+)CD25(-) and CD8(+)CD25(-)
      subsets of RC were isolated from blood of 25 cancer patients and 15 normal
      controls and cocultured in the presence of OKT3 and IL-2 (150 or 1000 IU/ml).
      Suppression of RC proliferation was measured in CFSE assays. RC and Treg
      apoptosis was monitored by 7-aminoactinomycin D staining in flow-based
      cytotoxicity assays. Treg from all subjects expressed CD95(+), but only Treg from
      cancer patients expressed CD95L. These Treg, when activated via TCR plus IL-2, up
      regulated CD95 and CD95L expression (p < 0.001) and suppressed CD8(+) RC
      proliferation (p < 0.001) by inducing Fas-mediated apoptosis. However, Treg
      cocultured with CD4(+) RC suppressed proliferation independently of Fas/FasL. In
      cocultures, Treg were found to be resistant to apoptosis in the presence of 1000
      IU/ml IL-2, but at lower IL-2 concentrations (150 IU/ml) they became susceptible
      to RC-induced death. Thus, Treg and RC can reciprocally regulate Treg survival,
      depending on IL-2 concentrations present in cocultures. This divergent IL-2
      dependent resistance or sensitivity of Treg and RC to apoptosis is amplified in
      patients with cancer.

PMID- 19155496
TI  - T cell leukemia/lymphoma 1 and galectin-1 regulate survival/cell death pathways
      in human naive and IgM+ memory B cells through altering balances in Bcl-2 family
      proteins.
AB  - BCR signaling plays a critical role in purging the self-reactive repertoire, or
      in rendering it anergic to establish self-tolerance in the periphery. Differences
      in self-reactivity between human naive and IgM(+) memory B cells may reflect
      distinct mechanisms by which BCR signaling dictates their survival and death.
      Here we demonstrate that BCR stimulation protected naive B cells from apoptosis
      with induction of prosurvival Bcl-2 family proteins, Bcl-x(L) and Mcl-1, whereas
      it rather accelerated apoptosis of IgM(+) memory B cells by inducing proapoptotic
      BH3-only protein Bim. We found that BCR-mediated PI3K activation induced the
      expression of Mcl-1, whereas it inhibited Bim expression in B cells.
      Phosphorylation of Akt, a downstream molecule of PI3K, was more sustained in
      naive than IgM(+) memory B cells. Abundant expression of T cell leukemia/lymphoma
      1 (Tcl1), an Akt coactivator, was found in naive B cells, and enforced expression
      of Tcl1 induced a high level of Mcl-1 expression, resulting in prolonged B cell
      survival. In contrast, Galectin-1 (Gal-1) was abundantly expressed in IgM(+)
      memory B cells, and inhibited Akt phosphorylation, leading to Bim up-regulation.
      Enforced expression of Gal-1 induced accelerated apoptosis in B cells. These
      results suggest that a unique set of molecules, Tcl1 and Gal-1, defines distinct
      BCR signaling cascades, dictating survival and death of human naive and IgM(+)
      memory B cells.

PMID- 19155498
TI  - B and T lymphocyte attenuator regulates B cell receptor signaling by targeting
      Syk and BLNK.
AB  - B and T lymphocyte attenuator (BTLA) functions as a negative regulator of T cell
      activation and proliferation. Although the role of BTLA in regulating T cell
      responses has been characterized, a thorough investigation into the precise
      molecular mechanisms involved in BTLA-mediated lymphocyte attenuation and, more
      specifically, its role in regulating B cell activation has not been presented. In
      this study, we have begun to elucidate the biochemical mechanisms by which BTLA
      functions to inhibit B cell activation. We describe the cell surface expression
      of BTLA on various human B cell subsets and confirm its ability to attenuate B
      cell proliferation upon associating with its known ligand, herpesvirus entry
      mediator (HVEM). BTLA associates with the BCR and, upon binding to HVEM, recruits
      the tyrosine phosphatase Src homology 2 domain-containing phosphatase 1 and
      reduces activation of signaling molecules downstream of the BCR. This is
      exemplified by a quantifiable decrease in tyrosine phosphorylation of the protein
      tyrosine kinase Syk, as measured by absolute quantification mass spectrometry.
      Furthermore, effector molecules downstream of BCR signaling, including the B cell
      linker protein, phospholipase Cgamma2, and NF-kappaB, display decreased
      activation and nuclear translocation, respectively, after BTLA activation by
      HVEM. These results begin to provide insight into the mechanism by which BTLA
      negatively regulates B cell activation and indicates that BTLA is an inhibitory
      coreceptor of the BCR signaling pathway and attenuates B cell activation by
      targeting the downstream signaling molecules Syk and B cell linker protein.

PMID- 19155497
TI  - Methylation status of CpG islands flanking a cAMP response element motif on the
      protein phosphatase 2Ac alpha promoter determines CREB binding and activity.
AB  - Protein phosphatase 2A (PP2A) is a major serine/threonine protein phosphatase in
      eukaryotic cells and is involved in many essential aspects of cell function. The
      catalytic subunit of the enzyme (PP2Ac), a part of the core enzyme, has two
      isoforms, alpha (PP2Ac alpha) and beta (PP2Ac beta), of which PP2Ac alpha is the
      major form expressed in vivo. Deregulation of PP2A expression has been linked to
      several diseases, but the mechanisms that control the expression of this enzyme
      are still unclear. We conducted experiments to decipher molecular mechanisms
      involved in the regulation of the PP2Ac alpha promoter in human primary T cells.
      After preparing serially truncated PP2Ac alpha promoter luciferase constructs, we
      found that the region stretching around 240 bases upstream from the translation
      initiation site was of functional significance and included a cAMP response
      element motif flanked by three GC boxes. Shift assays revealed that
      CREB/phosphorylated CREB and stable protein 1 could bind to the region.
      Furthermore, we demonstrated that methylation of deoxycytosine in the CpG islands
      limited binding of phosphorylated CREB and the activity of the PP2Ac alpha
      promoter. In contrast, the binding of stable protein 1 to a GC box within the
      core promoter region was not affected by DNA methylation. Primary T cells treated
      with 5-azacitidine, a DNA methyltransferase inhibitor, showed increased
      expression of PP2Ac alpha mRNA. We propose that conditions associated with
      hypomethylation of CpG islands, such as drug-induced lupus, permit increased
      PP2Ac expression.

PMID- 19155499
TI  - Complement inhibitor C4b-binding protein interacts directly with small
      glycoproteins of the extracellular matrix.
AB  - Components derived from cartilage have been suggested to maintain the
      inflammation in joints in arthritis. Small leucine-rich repeat proteins (SLRPs)
      are structural components of cartilage important in organizing the meshwork of
      extracellular matrix components. It has recently been shown that the SLRP
      fibromodulin interacts with complement initiator C1q, leading to complement
      activation. The complement response is limited since fibromodulin also interacts
      with the complement inhibitor factor H. We have now found that osteoadherin,
      chondroadherin, fibromodulin, and proline arginine-rich end leucine-rich repeat
      protein bind to the complement inhibitor C4b-binding protein (C4BP). Using direct
      binding assays with C4BP fragments and C4BP mutants lacking individual domains in
      combination with electron microscopy, we have demonstrated that mainly the
      central core of C4BP mediated binding to SLRPs. Binding of SLRPs to C4BP did not
      affect its ability to inhibit complement. Osteoadherin, fibromodulin, and
      chondroadherin, which bind C1q and activate complement, were found to cause
      significantly higher C9 deposition in C4BP-depleted serum compared with Igs,
      indicating that the level of complement activation initiated by SLRPs is
      regulated by simultaneous binding to C4BP. A similar dual binding of C1q and
      complement inhibitors was observed previously for other endogenous ligands
      (amyloid, prions, C-reactive protein, and apoptotic cells) but not for exogenous
      activators (bacteria-bound Igs). These interactions can be significant during
      inflammatory joint diseases, such as rheumatoid arthritis, where cartilage is
      degraded, and cartilage components are released into synovial fluid, where they
      can interact with factors of the complement system.

PMID- 19155500
TI  - A comparative study of HLA binding affinity and ligand diversity: implications
      for generating immunodominant CD8+ T cell responses.
AB  - Conventional CD8(+) T cell responses against intracellular infectious agents are
      initiated upon recognition of pathogen-derived peptides presented at the cell
      surface of infected cells in the context of MHC class I molecules. Among the
      major MHC class I loci, HLA-B is the swiftest evolving and the most polymorphic
      locus. Additionally, responses restricted by HLA-B molecules tend to be dominant,
      and most associations with susceptibility or protection against infectious
      diseases have been assigned to HLA-B alleles. To assess whether the differences
      in responses mediated via two major HLA class I loci, HLA-B and HLA-A, may
      already begin at the Ag presentation level, we have analyzed the diversity and
      binding affinity of their peptide repertoire by making use of curated pathogen
      derived epitope data retrieved from the Immune Epitope Database and Analysis
      Resource, as well as in silico predicted epitopes. In contrast to our
      expectations, HLA-B alleles were found to have a less diverse peptide repertoire,
      which points toward a more restricted binding motif, and the respective average
      peptide binding affinity was shown to be lower than that of HLA-A-restricted
      epitopes. This unexpected observation gives rise to new hypotheses concerning the
      mechanisms underlying immunodominance of CD8(+) T cell responses.

PMID- 19155501
TI  - A novel activating chicken IgY FcR is related to leukocyte receptor complex (LRC)
      genes but is located on a chromosomal region distinct from the LRC and FcR gene
      clusters.
AB  - FcRs have multifaceted roles in the immune system. Chicken FcRs were demonstrated
      on macrophages decades ago; however, only recently the chicken Ig-like receptor
      AB1, encoded in the leukocyte receptor complex, was molecularly identified as a
      high-affinity FcR. The present study was initiated to identify additional
      receptors with the capability to bind chicken immunoglobulins. Based on database
      searches, we cloned a novel chicken FcR, designated gallus gallus FcR (ggFcR),
      which was shown to bind selectively chicken IgY. The receptor consists of four
      extracellular C2-set Ig domains, followed by a transmembrane region containing
      arginine as a positively charged amino acid and a short cytoplasmic tail. ggFcR
      associates with the common gamma-chain, indicative for an activating receptor,
      and real-time RT-PCR revealed high expression on PBMC, thrombocytes, and
      macrophages. The genomic organization is similar to most Ig-like receptor genes,
      where each Ig domain is encoded by a separate exon. Additionally, the ggFcR
      signal peptide is encoded by two exons, the second of which is 36 bp, a hallmark
      for genes encoded in the leukocyte receptor complex. Phylogenetic analysis also
      showed a relationship to genes encoded in the leukocyte receptor complex.
      Surprisingly, ggFcR is not encoded in the leukocyte receptor complex, but it is
      located as a single isolated gene at the extremity of chicken chromosome 20.

PMID- 19155502
TI  - Soluble IL-2RA levels in multiple sclerosis subjects and the effect of soluble IL
      2RA on immune responses.
AB  - Multiple sclerosis (MS) is an organ-specific autoimmune disorder that is in part
      genetically determined. The gene encoding the alpha-chain of the IL-2 receptor,
      IL2RA, harbors alleles associated with risk to MS and other autoimmune diseases.
      In addition, IL2RA genetic variants correlate with the levels of a soluble form
      of the IL-2 receptor in subjects with type 1 diabetes and multiple sclerosis.
      Here, we show that the IL2RA genotypes differentially affects soluble IL-2RA (sIL
      2RA) levels in MS cases vs healthy controls; the two variants associated with MS
      (rs12722489 and rs2104286) account for 15 and 18% of the total variance in
      log(10)-transformed sIL-2RA concentration in control subjects but less so in
      subjects with MS (2 and 5%), suggesting that perturbations associated with
      disease or treatment may influence sIL-2RA levels in subjects with MS. Whereas
      analyses demonstrate that sIL-2RA serum concentrations are a remarkably stable
      phenotype in both healthy controls and untreated MS subjects, a difference is
      observed between benign and malignant MS. These data indicate that, in addition
      to specific allelic variants at IL2RA, immunological perturbations associated
      with aggressive forms of the disease can influence sIL-2RA levels in serum of MS
      subjects. We also demonstrate, functionally, that sIL-2RA can inhibit IL-2
      signaling, yet enhance T cell proliferation and expansion. In summary, we propose
      that before disease onset, strong genetic factors associated with disease risk
      dictate sIL-2RA levels that may be further modulated with onset of chronic
      systemic inflammation associated with MS.

PMID- 19155504
TI  - Surfactant protein A enhances production of secretory leukoprotease inhibitor and
      protects it from cleavage by matrix metalloproteinases.
AB  - Mice lacking surfactant protein A (SP-A) are susceptible to bacterial infection
      associated with an excessive inflammatory response in the lung. To determine
      mechanisms by which SP-A is antiinflammatory in the lung during bacterial
      infection, SP-A regulation of secretory leukoprotease inhibitor (SLPI), an
      inhibitor of serine proteases, was assessed. SLPI protein expression and
      antineutrophil elastase activity were reduced in bronchoalveolar fluid of SP-A(-/
      ) compared with SP-A(+/+) mice. Intratracheal administration of SP-A to SP-A(-/-)
      mice enhanced SLPI protein expression and antineutrophil elastase activity in the
      lung. SLPI mRNA was similar in whole lung and alveolar type II cells; however, it
      was significantly reduced in alveolar macrophages from SP-A(-/-) compared with SP
      A(+/+) mice. In vitro, SP-A enhanced SLPI production by macrophage THP-1 cells
      but not respiratory epithelial A549 cells. SP-A inhibited LPS induced IkappaB
      alpha degradation in THP-1 cells, which was partially reversed with knockdown of
      SLPI. Matrix metalloproteinase (MMP)-12 cleaved SLPI and incubation with SP-A
      reduced MMP-12-mediated SLPI cleavage. The collagen-like region of SP-A conferred
      protection of SLPI against MMP mediated cleavage. SP-A plays an important role in
      the lung during bacterial infection regulating protease and antiprotease
      activity.

PMID- 19155503
TI  - Cytomegalovirus-infected human endothelial cells can stimulate allogeneic CD4+
      memory T cells by releasing antigenic exosomes.
AB  - Human CMV infection is controlled by T cell-mediated immunity and in
      immunosuppressed transplant patients it is associated with acute allograft
      rejection as well as chronic allograft vasculopathy. CMV infects endothelial
      cells (EC) and it is thought that CMV-specific host immune responses to infected
      allograft EC contribute to rejection. In vitro, CD4(+) T cells from CMV-positive
      donors (but not CMV-negative donors) are readily activated by CMV-infected
      allogeneic EC, although it is unclear how allogeneic CMV-infected EC activate
      self-class II MHC-restricted memory CD4(+) T cells. In this study, we confirm
      that purified CD4(+) T cells from CMV(+) donors are activated by allogeneic CMV
      infected EC, but find that the response is dependent upon copurified APC
      expressing class II MHC that are autologous to the T cells. The transfer of CMV
      Ags from infected EC to APC can be mediated by EC-derived exosome-like particles.
      These results provide a mechanism by which CMV can exacerbate allograft rejection
      and suggest a novel function of EC-derived exosomes that could contribute in a
      more general manner to immune surveillance.

PMID- 19155505
TI  - Acute alcohol intoxication inhibits the lineage- c-kit+ Sca-1+ cell response to
      Escherichia coli bacteremia.
AB  - Alcohol abuse predisposes the host to bacterial infections. In response to
      bacterial infection, the bone marrow hematopoietic activity shifts toward
      granulocyte production, which is critical for enhancing host defense. This study
      investigated the hematopoietic precursor cell response to bacteremia and how
      alcohol affects this response. Acute alcohol intoxication was induced in BALB/c
      mice 30 min before initiation of Escherichia coli bacteremia. Bacteremia caused a
      significant increase in the number of bone marrow lineage (lin(-))-c-kit(+)Sca
      1(+) cells. Marrow lin(-)c-kit(+)Sca-1(+) cells isolated from bacteremic mice
      showed an increase in CFU-granulocyte/macrophage activity compared with controls.
      In addition to enhanced proliferation of lin(-)c-kit(+)Sca-1(+) cells as
      reflected by BrdU incorporation, phenotypic inversion of lin(-)c-kit(+)Sca
      1(+)Sca-1(-) cells primarily accounted for the rapid increase in marrow lin(-)c
      kit(+)Sca-1(+) cells following bacteremia. Bacteremia increased plasma
      concentration of TNF-alpha. Culture of marrow lin(-)c-kit(+)Sca-1(+)Sca-1(-)
      cells with murine rTNF-alpha for 24 h caused a dose-dependent increase in
      conversion of these cells to lin(-)c-kit(+)Sca-1(+) cells. Sca-1 mRNA expression
      by the cultured cells was also up-regulated following TNF-alpha stimulation.
      Acute alcohol intoxication inhibited the increase in the number of lin(-)c
      kit(+)Sca-1(+) cells in the bone marrow after E. coli infection. Alcohol impeded
      the increase in BrdU incorporation into marrow lin(-)c-kit(+)Sca-1(+) cells in
      response to bacteremia. Alcohol also suppressed the plasma TNF-alpha response to
      bacteremia and inhibited TNF-alpha-induced phenotypic inversion of lin(-)c
      kit(+)Sca-1(+)Sca-1(-) cells in vitro. These data show that alcohol inhibits the
      hematopoietic precursor cell response to bacteremia, which may serve as one
      mechanism underlying the impaired host defense in alcohol abusers with severe
      bacterial infections.

PMID- 19155507
TI  - Is Porphyromonas gingivalis cell invasion required for atherogenesis?
      Pharmacotherapeutic implications.
AB  - Various studies have demonstrated an association between chronic bacterial
      infections and atherosclerotic cardiovascular disease. Porphyromonas gingivalis,
      which can invade endothelial cells, is one pathogen that may link these
      disorders. If so, antibiotics that block its invasiveness may ameliorate
      atherosclerotic plaque progression. To explore the role of invasion of P.
      gingivalis in inflammation- and infection-associated atherosclerosis, 10-wk-old
      ApoE(+/-) mice were fed either a high fat diet or a regular chow diet. All mice
      were inoculated i.v., once per week for 24 consecutive wk, with either 50 microl
      of live P. gingivalis (strain 381) (10(7) CFU); a fimbria-deficient P.
      gingivalis; or metronidazole before P. gingivalis. Mice were euthanized and
      evaluated 24 wk after the first inoculation. ApoE(+/-) mice injected with DPG3 or
      metronidazole showed significantly fewer atheromatous lesions in the proximal
      aorta and the aortic tree compared with ApoE(+/-) mice injected with wild-type P.
      gingivalis for either diet condition. Serum amyloid A levels were significantly
      lower in ApoE(+/-) mice that received either DPG3 or metronidazole before P.
      gingivalis than from ApoE(+/-) mice that received P. gingivalis alone. Serum
      cytokine analysis revealed decreased levels of proinflammatory cytokines in both
      DPG3-injected and metronidazole/P. gingivalis-treated ApoE(+/-) mice compared
      with mice receiving only P. gingivalis, irrespective of diet. P. gingivalis
      invasion is a critical phenomenon in the progression of atherosclerosis. The
      present data offer new insights into the pathophysiological pathways involved in
      atherosclerosis and pave the way for new pharmacological interventions aimed at
      reducing atherosclerosis.

PMID- 19155506
TI  - Eosinophil deficiency compromises parasite survival in chronic nematode
      infection.
AB  - Immune responses elicited by parasitic worms share many features with those of
      chronic allergy. Eosinophils contribute to the inflammation that occurs in both
      types of disease, and helminths can be damaged or killed by toxic products
      released by eosinophils in vitro. Such observations inform the widely held view
      that eosinophils protect the host against parasitic worms. The mouse is a natural
      host for Trichinella spiralis, a worm that establishes chronic infection in
      skeletal muscle. We tested the influence of eosinophils on T. spiralis infection
      in two mouse strains in which the eosinophil lineage is ablated. Eosinophils were
      prominent in infiltrates surrounding infected muscle cells of wild-type mice;
      however, in the absence of eosinophils T. spiralis muscle larvae died in large
      numbers. Parasite death correlated with enhanced IFN-gamma and decreased IL-4
      production. Larval survival improved when mice were treated with inhibitors of
      inducible NO synthase, implicating the NO pathway in parasite clearance. Thus,
      the long-standing paradigm of eosinophil toxicity in nematode infection requires
      reevaluation, as our results suggest that eosinophils may influence the immune
      response in a manner that would sustain chronic infection and insure worm
      survival in the host population. Such a mechanism may be deployed by other
      parasitic worms that depend upon chronic infection for survival.

PMID- 19155508
TI  - A signaling polypeptide derived from an innate immune adaptor molecule can be
      harnessed as a new class of vaccine adjuvant.
AB  - Modulation of intracellular signaling using cell-permeable polypeptides is a
      promising technology for future clinical applications. To develop a novel
      approach to activate innate immune signaling by synthetic polypeptides, we
      characterized several different polypeptides derived from the caspase recruitment
      domain (CARD) of IFN-beta promoter stimulator 1, each of which localizes to a
      different subcellular compartment. Of particular interest was, N'-CARD, which
      consisted of the nuclear localization signal of histone H2B and the IFN-beta
      promoter stimulator 1CARD and which localized to the nucleus. This polypeptide
      led to a strong production of type I IFNs and molecular and genetic analyses
      showed that nuclear DNA helicase II is critically involved in this response. N'
      CARD polypeptide fused to a protein transduction domain (N'-CARD-PTD) readily
      transmigrated from the outside to the inside of the cell and triggered innate
      immune signaling. Administration of N'-CARD-PTD polypeptide elicited production
      of type I IFNs, maturation of bone marrow-derived dendritic cells, and promotion
      of vaccine immunogenicity by enhancing Ag-specific Th1-type immune responses,
      thereby protecting mice from lethal influenza infection and from outgrowth of
      transplanted tumors in vivo. Thus, our results indicate that the N'-CARD-PTD
      polypeptide belongs to a new class of vaccine adjuvant that directly triggers
      intracellular signal transduction by a distinct mechanism from those engaged by
      conventional vaccine adjuvants, such as TLR ligands.

PMID- 19155509
TI  - Novel Chlamydia muridarum T cell antigens induce protective immunity against lung
      and genital tract infection in murine models.
AB  - Using a combination of affinity chromatography and tandem mass spectrometry, we
      recently identified 8 MHC class II (I-A(b)) -bound Chlamydia peptides eluted from
      dendritic cells (DCs) infected with Chlamydia muridarum. In this study we cloned
      and purified the source proteins that contained each of these peptides and
      determined that three of the eight peptide/protein Ags were immunodominant (PmpG
      1, RplF, and PmpE/F-2) as identified by IFN-gamma ELISPOT assay using splenocytes
      from C57BL/6 mice recovered from C. muridarum infection. To evaluate whether the
      three immunodominant Chlamydia protein Ags were also able to protect mice against
      Chlamydia infection in vivo, we adoptively transferred LPS-matured DCs
      transfected ex vivo with the cationic liposome DOTAP (N-[1-(2,3
      dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate) and individual PmpG
      1(25-500aa), RplF, or PmpE/F-2 (25-575 aa) proteins. The results showed that the
      transfected Chlamydia proteins were efficiently delivered intracellularly into
      DCs. Mice vaccinated with DCs transfected with individual Chlamydia protein PmpG
      1(25-500), RplF, or PmpE/F-2(25-575) exhibited significant resistance to
      challenge infection as indicated by reduction in the median Chlamydia inclusion
      forming units in both the lung and genital tract models. The major outer membrane
      protein was used as a reference Ag but conferred significant protection only in
      the genital tract model. Overall, vaccination with DCs transfected with PmpG-1(25
      500) exhibited the greatest degree of protective immunity among the four
      Chlamydia Ags tested. This study demonstrates that T cell peptide Ags identified
      by immunoproteomics can be successfully exploited as T cell protein-based subunit
      vaccines and that PmpG-1(25-500) protein may be a suitable vaccine candidate for
      further evaluation.

PMID- 19155510
TI  - Beta-defensin-2 promotes resistance against infection with P. aeruginosa.
AB  - Corneal infection with Pseudomonas aeruginosa results in corneal perforation in
      susceptible C57BL/6 (B6) mice, but not in resistant BALB/c mice. To explore the
      role of two important defensins, murine beta-defensin-1 (mBD1) and mBD2, in the
      ocular immune defense system, their mRNA and protein expression levels were
      tested by real-time RT-PCR and Western blot, respectively. mRNA, protein, and
      immunostaining data demonstrated that both mBD1 and mBD2 were constitutively
      expressed in normal BALB/c and B6 corneas, and they were disparately up-regulated
      in BALB/c (more) vs B6 (less) corneas after infection. To determine whether
      either defensin played a role in host resistance, BALB/c mice were treated with
      either mBD1 or mBD2 small interfering RNA by subconjunctival injection together
      with topical application. Increased corneal opacity and worsened disease were
      displayed after knockdown of mBD2 but not of mBD1. mBD2 silencing also increased
      bacterial counts and polymorphonuclear neutrophil infiltration in BALB/c corneas.
      Real-time RT-PCR data further demonstrated that mBD2, not mBD1, differentially
      modulated mRNA expression of proinflammatory cytokines/molecules such as IFN
      gamma, MIP-2, IL-1beta, TNF-alpha, IL-6, and inducible NO synthase; TLR signaling
      molecules, including TLR2, TLR4, TLR9, and MyD88; and the transcription factor NF
      kappaB. Additionally, in vivo studies indicated that mBD2 silencing enhanced
      corneal nitrite levels and NF-kappaB activation. Collectively, the data provide
      evidence that mBD2, but not mBD1, is required for host resistance against P.
      aeruginosa-induced corneal infection.

PMID- 19155511
TI  - The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway
      inflammation.
AB  - IL-17 is the signature cytokine of recently discovered Th type 17 (Th17) cells,
      which are prominent in defense against extracellular bacteria and fungi as well
      as in autoimmune diseases, such as rheumatoid arthritis and experimental
      autoimmune encephalomyelitis in animal models. IL-25 is a member of the IL-17
      family of cytokines, but has been associated with Th2 responses instead and may
      negatively cross-regulate Th17/IL-17 responses. IL-25 can initiate an allergic
      asthma-like inflammation in the airways, which includes recruitment of
      eosinophils, mucus hypersecretion, Th2 cytokine production, and airways
      hyperreactivity. We demonstrate that these effects of IL-25 are entirely
      dependent on the adaptor protein CIKS (also known as Act1). Surprisingly, this
      adaptor is necessary to transmit IL-17 signals as well, despite the very distinct
      biologic responses that these two cytokines elicit. We identify CD11c(+)
      macrophage-like lung cells as physiologic relevant targets of IL-25 in vivo.

PMID- 19155512
TI  - The critical role of epithelial-derived Act1 in IL-17- and IL-25-mediated
      pulmonary inflammation.
AB  - IL-25 initiates, promotes, and augments Th2 immune responses. In this study, we
      report that Act1, a key component in IL-17-mediated signaling, is an essential
      signaling molecule for IL-25 signaling. Although Act1-deficient mice showed
      reduced expression of KC (CXCL1) and neutrophil recruitment to the airway
      compared with wild-type mice in response to IL-17 stimulation, Act1 deficiency
      abolished IL-25-induced expression of IL-4, IL-5, IL-13, eotaxin-1 (CCL11), and
      pulmonary eosinophilia. Using a mouse model of allergic pulmonary inflammation,
      we observed diminished Th2 responses and lung inflammation in Act1-deficient mice
      compared with wild-type mice. Importantly, Act1 deficiency in epithelial cells
      reduced the phenotype of allergic pulmonary inflammation due to loss of IL-17
      induced neutrophilia and IL-25-induced eosinophilia, respectively. These results
      demonstrate the essential role of epithelial-derived Act1 in allergic pulmonary
      inflammation through the distinct impact of the IL-17R-Act1 and IL-25R-Act1 axes.
      Such findings are crucial for the understanding of pathobiology of atopic
      diseases, including allergic asthma, which identifies Act1 as a potential
      therapeutic target.

PMID- 19155513
TI  - TSLP conditions the lung immune environment for the generation of pathogenic
      innate and antigen-specific adaptive immune responses.
AB  - Thymic stromal lymphopoietin (TSLP) is crucial for the development of atopic
      diseases in humans and mice. Mice that express a lung-specific TSLP transgene
      (surfactant protein C promoter (SPC)-TSLP) develop a spontaneous and progressive
      asthma-like disease, suggesting that TSLP expression alone was sufficient for
      disease development. In this study, we show that, in fact, TSLP alone only causes
      a weak innate response that is insufficient for development of full airway
      inflammatory disease. Complete disease development requires both TSLP and
      antigenic stimulation. These data suggest that the spontaneous lung inflammation
      observed in SPC-TSLP mice reflects a TSLP-driven predisposition toward the
      development of aberrant responses against innocuous environmental Ags. This
      provides evidence that TSLP may act directly to induce susceptibility to the
      inappropriate allergic responses that characterize atopy and asthma. We
      additionally show that disease development requires CD4 T cells but not B cells.
      Further, we reveal a TSLP-driven innate response involving mucus overproduction
      and goblet cell metaplasia. Taken together, these data suggest a multifaceted
      model of TSLP-mediated airway inflammation, with an initial activation of
      resident innate immune cells, followed by activation of the adaptive immune
      system and full disease development. This study provides new insight into the
      unique features of the asthma pathology contributed by the innate and adaptive
      immune responses in response to TSLP stimulation.

PMID- 19155514
TI  - Myeloid-specific expression of Api6/AIM/Sp alpha induces systemic inflammation
      and adenocarcinoma in the lung.
AB  - To study the functional role of apoptosis inhibition of myeloid lineage cells in
      tumor formation, apoptosis inhibitor 6 (Api6/AIM/Sp alpha) was overexpressed in a
      myeloid-specific c-fms-rtTA/(TetO)(7)-CMV-Api6 bitransgenic mouse model under the
      control of the c-fms promoter/intron 2. In this bitransgenic system, the Api6
      Flag fusion protein was expressed in myeloid lineage cells after doxycycline
      treatment. Induction of Api6 abnormally elevated levels of macrophages,
      neutrophils, and dendritic cells in the bone marrow, blood, and lung in vivo.
      BrdU incorporation and annexin V binding studies showed systemically increased
      cell proliferation and inhibition of apoptosis in myeloid lineage cells. Api6
      overexpression activated oncogenic signaling pathways, including Stat3, Erk1/2,
      and p38 in myeloid lineage cells in multiple organs of the bitransgenic mice. In
      the lung, severe inflammation and massive tissue remodeling were observed in
      association with increased expression of procancer cytokines/chemokines,
      decreased expression of proapoptosis molecule genes, and increased expression of
      matrix metalloproteinase genes as a result of Api6 overexpression. Oncogenic
      CD11b(+)/Gr-1(+) myeloid-derived suppressor cells were systemically increased.
      After Api6 overexpression, lung adenocarcinoma was observed in bitransgenic mice
      with a 35% incidence rate. These studies suggest that dysregulation of myeloid
      cell populations by extracellular Api6 signaling leads to abnormal myelopoiesis
      and lung cancer.

PMID- 19155516
TI  - Dendritic cell-based therapeutic vaccination against myeloma: vaccine formulation
      determines efficacy against light chain myeloma.
AB  - Multiple myeloma is an incurable plasma cell malignancy. Immunotherapy in myeloma
      patients had limited success to date. We have previously demonstrated that
      dendritic cells (DCs) pulsed with autologous Ig Id induced Id-reactive CD8(+) T
      cells and protection against a myeloma tumor challenge. In this work, we studied
      the therapeutic efficacy of chemotherapy combined with different formulations of
      DC-based vaccines in mice bearing large plasma cell tumors. The comparative study
      demonstrated that s.c. injection of DCs loaded with Id coupled to keyhole limpet
      hemocyanin, s.c. injection of DCs loaded with irradiated tumor cells, and
      intratumoral injection of naive DCs were similarly effective in mediating tumor
      regression and long-term survival. However, whereas the Id-keyhole limpet
      hemocyanin-DC vaccine was inefficient against myeloma cells that lost expression
      of the Ig H chain, intratumoral injection of naive DCs and s.c. injection of DCs
      loaded with irradiated tumor cells were highly effective against cells producing
      L chains only. This may be of particular importance for patients with L chain
      myeloma. Given that T cells respond primarily to peptides derived from H chain
      CDRs, attempts to treat L chain disease with myeloma protein-pulsed DCs may be
      futile. Vaccination with tumor cell-loaded DCs may, however, induce an effective
      antitumor response.

PMID- 19155515
TI  - IL-17 signaling for mRNA stabilization does not require TNF receptor-associated
      factor 6.
AB  - IL-17 alone is a relatively weak inducer of gene expression, but cooperates with
      other cytokines, including TNF-alpha, to generate a strong response in part via
      prolongation of mRNA t(1/2). Because TNFR-associated factor 6 (TRAF6) has been
      reported to be essential for signaling by IL-17, we examined its involvement in
      IL-17-mediated mRNA stabilization. Although overexpression of TRAF6 in HeLa cells
      activates NF-kappaB, it does not stabilize transfected KC mRNA. Furthermore, a
      dominant-negative TRAF6 abrogates NF-kappaB activation, but does not block IL-17
      induced chemokine mRNA stabilization. IL-17 can stabilize KC and MIP-2 mRNAs
      comparably in TNF-alpha-treated mouse embryo fibroblasts from TRAF6(+/+) and
      TRAF6(-/-) mice. TRAF6 is known to couple upstream signals with activation of p38
      MAPK and mitogen activated protein kinase activated protein kinase 2, both of
      which have been shown to be important for Toll/IL-1R-mediated mRNA stabilization
      in various cell types. Inhibition of p38 MAPK, however, does not block IL-17
      induced KC mRNA stabilization, and IL-17 can stabilize KC mRNA equally in mouse
      embryo fibroblasts from both wild-type and mitogen activated protein kinase
      activated protein kinase 2/3 doubly-deficient mice. Finally, IL-17 can amplify
      the levels of multiple TNF-alpha-stimulated mRNAs in wild-type and TRAF6
      deficient cells, but not in cells from Act1(-/-) mice. Collectively, these
      findings demonstrate the existence of a TRAF6/p38 MAPK-independent pathway that
      couples the IL-17R with enhanced mRNA stability. Because the most potent effects
      of IL-17 on gene expression are obtained in cooperation with other cytokines such
      as TNF-alpha, these findings suggest that this pathway is a major contributing
      mechanism for response to IL-17.

PMID- 19155517
TI  - Novel autoantibodies against the activated coagulation factor IX (FIXa) in the
      antiphospholipid syndrome that interpose the FIXa regulation by antithrombin.
AB  - We previously reported that some human antiphospholipid Abs (aPL) in patients
      with the antiphospholipid syndrome (APS) bind to the homologous enzymatic domains
      of thrombin and the activated coagulation factor X (FXa). Moreover, some of the
      reactive Abs are prothrombotic and interfere with inactivation of thrombin and
      FXa by antithrombin (AT). Considering the enzymatic domain of activated
      coagulation factor IX (FIXa) is homologous to those of thrombin and FXa, we
      hypothesized that some aPLs in APS bind to FIXa and hinder AT inactivation of
      FIXa. To test this hypothesis, we searched for IgG anti-FIXa Abs in APS patients.
      Once the concerned Abs were found, we studied the effects of the Ab on FIXa
      inactivation by AT. We found that 10 of 12 patient-derived monoclonal IgG aPLs
      bound to FIXa and that IgG anti-FIXa Abs in APS patients were significantly
      higher than those in normal controls (p < 0.0001). Using the mean + 3 SD of 30
      normal controls as the cutoff, the IgG anti-FIXa Abs were present in 11 of 38
      (28.9%) APS patients. Importantly, 4 of 10 FIXa-reactive monoclonal aPLs
      (including the B2 mAb generated against beta(2)-glycoprotein I significantly
      hindered AT inactivation of FIXa. More importantly, IgG from two positive plasma
      samples were found to interfere with AT inactivation of FIXa. In conclusion, IgG
      anti-FIXa Ab occurred in approximately 30% of APS patients and could interfere
      with AT inactivation of FIXa. Because FIXa is an upstream procoagulant factor,
      impaired AT regulation of FIXa might contribute more toward thrombosis than the
      dysregulation of the downstream FXa and thrombin.

PMID- 19155518
TI  - Unique phenotypes of C1s deficiency and abnormality caused by two compound
      heterozygosities in a Japanese family.
AB  - A deficiency in the early components of complement is associated with an
      increased susceptibility to pyrogenic infections and multiple autoimmune
      diseases. We previously reported a Japanese case of selective C1s deficiency
      resulting from a compound heterozygosity for a 4-bp deletion in exon X and a
      nonsense mutation Glu597X in exon XII of the C1s gene. In this previous case, the
      patient suffered from unique symptoms including virus-associated hemophagocytic
      syndrome and died after a long period of loss of consciousness. In the present
      study, we report another patient from the same family, with C1s abnormality
      caused by a distinct compound-heterozygous genotype and who had a novel missense
      mutation Gly630Glu transmitted from the mother's side and a previously identified
      nonsense mutation Glu597X from the father's side. Thus three distinct mutations
      of the C1s gene were clustered and resulted in two distinct genotypes for C1s
      deficiency and C1s abnormality within this one family. The present patient showed
      symptoms that were similar in part to our previous patient, which were different
      from those of the cases reported in other families. The biochemical properties of
      C1s in the patient's serum and the recombinant form were closely related to the
      undetectable or very low activity of complement activation. These results
      suggested that the uniqueness and severity of the symptoms observed here in the
      two patients might be under the control of a common C1s allele and distinct
      counterparts, respectively.

PMID- 19155519
TI  - Phenotypic and functional analysis of CD4+ CD25- Foxp3+ T cells in patients with
      systemic lupus erythematosus.
AB  - CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) that specialize in the
      suppression of immune responses might be critically involved in the pathogenesis
      of autoimmune diseases. Recent studies have described increased proportions of
      CD4(+)Foxp3(+) T cells that lacked expression of CD25 in systemic lupus
      erythematosus (SLE) patients but the suppressive capacity of these cells has not
      been analyzed so far. We therefore performed combined phenotypic and functional
      analyses of CD4(+)CD25(-)Foxp3(+) T cells in patients with autoimmune diseases
      and healthy controls (HC). Phenotypic analysis revealed increased proportions of
      CD4(+)CD25(-)Foxp3(+) T cells in SLE patients as compared with patients with
      systemic sclerosis, rheumatoid arthritis, (RA), or HC. In addition, increased
      proportions of CD4(+)CD25(-)Foxp3(+) T cells correlated with the clinical disease
      activity and the daily cortisone dose. According to phenotypic analysis,
      CD4(+)CD25(-)Foxp3(+) T cells resembled regulatory T cells rather than activated
      T cells. For functional analysis, a surrogate surface marker combination to
      substitute for intracellular Foxp3 was defined: CD4(+)CD25(-)CD127(-) T cells
      from SLE patients were isolated by FACS sorting and analyzed for their
      suppressive capacity in vitro. CD4(+)CD25(-)CD127(-) T cells, that contained up
      to 53% Foxp3(+) T cells, were found to suppress T cell proliferation but not IFN
      gamma production in vitro. In summary, CD4(+)CD25(-)Foxp3(+) T cells
      phenotypically and to a certain extent also functionally resemble conventional
      Treg. Despite increased proportions, however, their selective functional defects
      might contribute to the failure of Treg to control autoimmune dysregulation in
      SLE patients.

PMID- 19155520
TI  - Oxidative stress mediates a reduced expression of the activating receptor NKG2D
      in NK cells from end-stage renal disease patients.
AB  - To characterize the immune defect of patients with end-stage renal disease
      (ESRD), we performed NK cell subset analysis in 66 patients with ESRD treated by
      hemodialysis (n = 59) or peritoneal dialysis (n = 7). Compared with healthy blood
      donors, patients undergoing chronic dialysis showed a profound decrease in
      NKG2D(+) cells within both the CD8(+) T cell (58% vs 67%, p = 0.03) and NK cell
      (39% vs 56%, p = 0.002) populations. CD56(dim) cells, which comprise the majority
      of NK cells in the periphery, were more affected in this regard than were
      CD56(bright) cells. Uremic serum could decrease NKG2D expression on NK cells from
      healthy donors. Among factors that could contribute to the decrease in NKG2D
      expression in ESRD patients, reactive oxygen species (ROS) play a major role. We
      found that catalase could reverse the effects of uremic serum on NKG2D expression
      (p < 0.001) and that ROS down-regulated NKG2D at the mRNA level and at the NK
      cell surface. Additionally, ESRD patients had both increased membrane-bound MHC
      class I-related chain A (MICA) on monocytes (p = 0.04) and increased soluble MICA
      (203 pg/ml vs 110 pg/ml; p < 0.001). Both ROS and uremic serum could
      significantly increase in vitro the expression of the NKG2D ligand MICA on the
      renal epithelial cell line HK-2. Taken together, these studies suggest for the
      first time that both low NKG2D expression and up-regulation of its ligand MICA
      are related to ROS production and may be involved in the immune deficiency of
      ESRD patients.

PMID- 19155522
TI  - Nicotinic attenuation of central nervous system inflammation and autoimmunity.
AB  - The expression of nicotinic acetylcholine receptors by neurons, microglia, and
      astrocytes suggests possibly diverse mechanisms by which natural nicotinic
      cholinergic signaling and exposure to nicotine could modulate immune responses
      within the CNS. In this study, we show that nicotine exposure significantly
      delays and attenuates inflammatory and autoimmune responses to myelin Ags in the
      mouse experimental autoimmune encephalomyelitis model. In the periphery, nicotine
      exposure inhibits the proliferation of autoreactive T cells and alters the
      cytokine profile of helper T cells. In the CNS, nicotine exposure selectively
      reduces numbers of CD11c(+) dendritic and CD11b(+) infiltrating monocytes and
      resident microglial cells and down-regulates the expression of MHC class II,
      CD80, and CD86 molecules on these cells. The results underscore roles of
      nicotinic acetylcholine receptors and nicotinic cholinergic signaling in
      inflammatory and immune responses and suggest novel therapeutic options for the
      treatment of inflammatory and autoimmune disorders, including those that affect
      the CNS.

PMID- 19155521
TI  - Gene expression patterns induced by HPV-16 L1 virus-like particles in leukocytes
      from vaccine recipients.
AB  - Human papillomavirus (HPV) virus-like particle (VLP) vaccines were recently
      licensed. Although neutralizing Ab titers are thought to be the main effectors of
      protection against infection, early predictors of long-term efficacy are not yet
      defined and a comprehensive understanding of innate and adaptive immune responses
      to vaccination is still lacking. Here, microarrays were used to compare the gene
      expression signature in HPV-16 L1 VLP-stimulated PBMCs from 17 vaccine and 4
      placebo recipients before vaccination and 1 mo after receiving the second
      immunization. Vaccination with a monovalent HPV-16 L1 VLP vaccine was associated
      with modulation of genes involved in the inflammatory/defense response, cytokine,
      IFN, and cell cycle pathways in VLP-stimulated PBMCs. Additionally, there was up
      regulation of probesets associated with cytotoxic (GZMB, TNFSF10) and regulatory
      (INDO, CTLA4) activities. The strongest correlations with neutralizing Ab titers
      were found for cyclin D2 (CCND2) and galectin (LGALS2). Twenty-two differentially
      expressed probesets were selected for confirmation by RT-PCR in an independent
      sample set. Agreement with microarray data was seen for more than two-thirds of
      these probesets. Up-regulation of immune/defense response genes by HPV-16 L1 VLP,
      in particular, IFN-induced genes, was observed in PBMCs collected before
      vaccination, with many of these genes being further induced following
      vaccination. In conclusion, we identified important innate and adaptive response
      related genes induced by vaccination with HPV-16 L1 VLP. Further studies are
      needed to identify gene expression signatures of immunogenicity and long-term
      protection with potential utility in prediction of long-term HPV vaccination
      outcomes in clinical trials.

PMID- 19155523
TI  - A single helper T cell clone is sufficient to commit polyclonal naive B cells to
      produce pathogenic IgG in experimental pemphigus vulgaris.
AB  - The development of naive B cells into IgG-producing memory B cells requires
      cognate T cell-B cell interaction in Ag-specific immune responses. It is unknown
      whether a single T cell clone is sufficient or whether multiple clones are
      necessary to induce polyclonal IgG production in vivo. We addressed this issue
      using a mouse model of pemphigus vulgaris, a fatal autoimmune blistering skin
      disease caused by IgG autoantibodies against desmoglein (Dsg) 3. We previously
      isolated several Dsg3-reactive T cell clones from Dsg3(-/-) mice. Among these,
      two pathogenic T cell clones induced anti-Dsg3 IgG production and the development
      of a pemphigus phenotype when adoptively transferred with unprimed B cells from
      Dsg3(-/-) mice. IgG Abs harvested from recipient mice reacted with at least three
      parts of the extracellular domain of Dsg3, as determined using domain-swapped
      Dsg3/Dsg1 molecules. The anti-Dsg3 IgGs included at least two subclasses among
      IgG1, IgG2a, IgG2b, and IgG3 in each mouse. The anti-Dsg3 IgG induced by Dsg3
      reactive T cell clones with primed B cells from Dsg3(-/-) mice also showed
      reactivity against different parts of the molecule, with a similar epitope
      distribution. Together, these results indicate that a single potent Dsg3-reactive
      T cell is sufficient to commit polyclonal naive B cells to produce pathogenic
      anti-Dsg3 IgG Abs and induce the PV phenotype. These findings provide an
      important framework for examining immunological mechanisms in Ab-mediated
      autoimmune diseases.

PMID- 19155525
TI  - Anti-endothelial antibodies interfere in apoptotic cell clearance and promote
      thrombosis in patients with antiphospholipid syndrome.
AB  - Antiphospholipid syndrome is an important cause of recurrent thrombotic events.
      The pathogenesis of the thrombosis remains unclear, but it has been suggested
      that anti-phospholipid Abs, which are laboratory markers for the disease and
      include species capable of binding to vascular endothelial cells, play an
      important role. We hypothesized that these anti-endothelial Abs promote
      thrombosis through interference with clearance of dying cells. We show that
      healthy endothelial cell monolayers effectively remove apoptotic endothelial
      cells, but this clearance is markedly inhibited by serum or IgG from patients
      with antiphospholipid syndrome and anti-endothelial Abs. In addition, patient
      sera or IgG opsonize apoptotic endothelial cells and cause enhanced Fc-mediated
      uptake by professional phagocytes. Importantly, the delayed clearance of
      apoptotic cells by healthy endothelial cells and the enhanced Fc-mediated
      macrophage uptake each result in procoagulant consequences, as judged by
      increased thrombin generation. The effects on apoptotic cell clearance were
      reproduced by a mAb derived from a patient with antiphospholipid syndrome, which
      binds to endothelial cells and is thrombogenic in experimental models. Taken
      together, our data support a novel, dual mechanism by which anti-endothelial Abs
      are prothrombotic in antiphospholipid syndrome by inhibiting removal of
      procoagulant apoptotic cells and by diverting their clearance to provoke
      inflammatory and prothrombotic changes in professional phagocytes.

PMID- 19155524
TI  - Disruption of CCR5-dependent homing of regulatory T cells inhibits tumor growth
      in a murine model of pancreatic cancer.
AB  - Tumors evade immune destruction by actively inducing immune tolerance through the
      recruitment of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg). We have
      previously described increased prevalence of these cells in pancreatic
      adenocarcinoma, but it remains unclear what mechanisms are involved in recruiting
      Tregs into the tumor microenvironment. Here, we postulated that chemokines might
      direct Treg homing to tumor. We show, in both human pancreatic adenocarcinoma and
      a murine pancreatic tumor model (Pan02), that tumor cells produce increased
      levels of ligands for the CCR5 chemokine receptor and, reciprocally, that CD4(+)
      Foxp3(+) Tregs, compared with CD4(+) Foxp3(-) effector T cells, preferentially
      express CCR5. When CCR5/CCL5 signaling is disrupted, either by reducing CCL5
      production by tumor cells or by systemic administration of a CCR5 inhibitor (N,N
      dimethyl-N-{{4-{[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8
      yl]carbonyl}amino}}benzyl]-N,N-dimethyl-N- {{{4-{{{[2-(4-methylphenyl)-6,7
      dihydro-5H-benzocycloheptan-8-yl]carbonyl}amino}}benzyl}}}tetrahydro-2H-pyran-4
      aminiumchloride; TAK-779), Treg migration to tumors is reduced and tumors are
      smaller than in control mice. Thus, this study demonstrates the importance of
      Tregs in immune evasion by tumors, how blockade of Treg migration might inhibit
      tumor growth, and, specifically in pancreatic adenocarcinoma, the role of CCR5 in
      the homing of tumor-associated Tregs. Selective targeting of CCR5/CCL5 signaling
      may represent a novel immunomodulatory strategy for the treatment of cancer.

PMID- 19155526
TI  - A novel antiangiogenic effect for telomerase-specific virotherapy through host
      immune system.
AB  - Soluble factors in the tumor microenvironment may influence the process of
      angiogenesis; a process essential for the growth and progression of malignant
      tumors. In this study, we describe a novel antiangiogenic effect of conditional
      replication-selective adenovirus through the stimulation of host immune reaction.
      An attenuated adenovirus (OBP-301, Telomelysin), in which the human telomerase
      reverse transcriptase promoter element drives expression of E1 genes, could
      replicate in and cause selective lysis of cancer cells. Mixed lymphocyte-tumor
      cell culture demonstrated that OBP-301-infected cancer cells stimulated PBMC to
      produce IFN-gamma into the supernatants. When the supernatants were subjected to
      the assay of in vitro angiogenesis, the tube formation of HUVECs was inhibited
      more efficiently than recombinant IFN-gamma. Moreover, in vivo angiogenic assay
      using a membrane-diffusion chamber system s.c. transplanted in nu/nu mice showed
      that tumor cell-induced neovascularization was markedly reduced when the chambers
      contained the mixed lymphocyte-tumor cell culture supernatants. The growth of
      s.c. murine colon tumors in syngenic mice was significantly inhibited due to the
      reduced vascularity by intratumoral injection of OBP-301. The antitumor as well
      as antiangiogenic effects, however, were less apparent in SCID mice due to the
      lack of host immune responses. Our data suggest that OBP-301 seems to have
      antiangiogenic properties through the stimulation of host immune cells to produce
      endogenous antiangiogenic factors such as IFN-gamma.

PMID- 19155527
TI  - Letter of retraction.

PMID- 19155528
TI  - Neuro2A differentiation by Galphai/o pathway.
AB  - Signaling from G(i/o)-coupled G protein-coupled receptors (GPCRs), such as the
      serotonin 1B, cannabinoid 1, and dopamine D2 receptors, inhibits cAMP production
      by adenylyl cyclases and activates protein kinases, such as Src, mitogen
      activated protein kinases 1 and 2, and Akt. Activation of these protein kinases
      results in stimulation of neurite outgrowth in the central nervous system (CNS)
      and in neuronal cell lines. This Connections Map traces downstream signaling
      pathways from G(i/o)-coupled GPCRs to key protein kinases and key transcription
      factors involved in neuronal differentiation. Components in the Science Signaling
      Connections Map are linked to Nature Molecule Pages. This interoperability
      provides ready access to detail that includes information about specific states
      for the nodes.

PMID- 19155529
TI  - Protein kinase activation loop autophosphorylation in cis: overcoming a Catch-22
      situation.
AB  - Autophosphorylation of the activation loop in cis is an underappreciated and
      poorly understood mode of activation of protein kinases. Here, I describe four
      examples of protein kinases that are activated in this way, concentrating on
      their biochemical properties and how their autophosphorylation in cis is
      achieved.

PMID- 19155530
TI  - Genome to kinome: species-specific peptide arrays for kinome analysis.
AB  - Tools for conducting high-throughput kinome analysis do not exist for many
      species. For example, two commonly used techniques for monitoring phosphorylation
      events are phosphorylation-specific antibodies and peptide arrays. The majority
      of phosphorylation-specific antibodies are for human or mouse targets, and the
      construction of peptide arrays relies on information from phosphorylation
      databases, which are similarly biased toward human and mouse data. This is a
      substantial obstacle because many species other than mouse represent important
      biological models. On the basis of the observation that phosphorylation events
      are often conserved across species with respect to their relative positioning
      within proteins and their biological function, we demonstrate that it is possible
      to predict the sequence contexts of phosphorylation events in other species for
      the production of peptide arrays for kinome analysis. Through this approach,
      genomic information can be rapidly used to create inexpensive, customizable,
      species-specific peptide arrays for high-throughput kinome analysis. We
      anticipate that these arrays will be valuable for investigating the conservation
      of biological responses across species, validating animal models of disease, and
      translating research to clinical applications.

PMID- 19155532
TI  - Regulation of amino acid transporters in the rat remnant kidney.
AB  - BACKGROUND: Partial renal ablation is associated with compensatory renal growth,
      significant azotaemia, a significant increase in fractional excretion of sodium
      and changes in solute transport. The present study evaluated the occurrence of
      adaptations in the remnant kidney, especially in renal amino acid transporters
      and sodium transporters and their putative role in sodium handling in the early
      stages (24 h and 1 week) after uninephrectomy. METHODS: Wistar rats aged 8 weeks
      old were submitted to renal ablation of the right kidney--Unx rats (n = 10). 24
      hours (n = 5) and 1 week (n = 5) after surgery, rats were anesthetized and the
      left kidney was removed. Urinary and plasmatic levels of catecholamines, sodium,
      urea and creatinine were measured. Gene expression of the amino acid and sodium
      transporters was determined by Real-time reverse transcription PCR. Protein
      expression was evaluated by Western blot using specific antibodies for the amino
      acid and sodium transporters. RESULTS: Uninephrectomized (Unx) rats for 24 h
      showed a lower urinary excretion of L-DOPA, dopamine and DOPAC than the
      corresponding Sham rats, accompanied by an increase in the expression of the
      Na(+)-K(+)-ATPase protein (64% increase). Unx rats for 1 week presented a
      hypertrophied remnant kidney, higher urine outflow and a approximately 2-fold
      increase in the fractional excretion of sodium. The NHE3 mRNA expression was
      significantly decreased in Unx rats throughout the study (approximately 20%
      decrease). LAT1 transcript and protein were consistently overexpressed at both 24
      h and 1 week after uninephrectomy. In contrast, 4F2hc and LAT2 transcript
      abundance was lower in 24-h Unx rats than in Sham rats (a 36% decrease in both
      cases). CONCLUSIONS: These results provide evidence that the renal expression of
      the amino acid transporters LAT1, LAT2 and 4F2hc and the sodium transporters
      Na(+)-K(+)-ATPase and NHE3 is differently regulated following unilateral
      nephrectomy. In conclusion, this study allowed us to characterize the renal
      adaptations in the early stages after uninephrectomy, which showed a combined
      interaction of multiple mechanisms regulating sodium homeostasis including the
      renal dopaminergic system, and the abundance of amino acid transporters and
      sodium transporters.

PMID- 19155531
TI  - Disordered mineral metabolism is not a risk factor for loss of residual renal
      function in dialysis patients.
AB  - BACKGROUND: Recent studies showed that mineral metabolism disorders are
      associated with renal function loss in pre-dialysis patients, but their effects
      in dialysis patients are less well established. We examined associations between
      parameters of mineral metabolism and loss of residual renal function (RRF) in
      dialysis patients. METHODS: We included 1468 incident haemodialysis (HD) and
      peritoneal dialysis (PD) patients who were not anuric at dialysis initiation from
      NECOSAD, a prospective multicentre cohort study. We studied the effects of plasma
      calcium, phosphorus, calcium-phosphorus product and intact PTH concentrations on
      loss of RRF. Cox regression models were applied to calculate relative risks of
      total loss of RRF, defined as anuria during the first 3 years of dialysis. The
      rate of decline of RRF over time was calculated using general linear mixed
      models. RESULTS: The mean (SD) age was 59 (15), 62% were men and 59% were treated
      with HD. We found that both HD and PD patients with the highest phosphorus (P <
      0.0001) and calcium-phosphorus product (P < 0.0001) levels had the lowest
      baseline residual glomerular filtration rate (rGFR) values. During follow-up, 136
      HD (15%) and 67 PD patients (12%) became anuric. After adjustment for baseline
      rGFR, there were no significant associations between parameters of mineral
      metabolism and the risk of becoming anuric. There were also no differences in the
      rate of decline in RRF between categories of plasma concentrations. CONCLUSION:
      Disordered mineral metabolism was neither associated with the risk of becoming
      anuric, nor with the rate of decline in RRF in dialysis patients. Differences in
      decline were mainly attributable to the baseline rGFR value.

PMID- 19155533
TI  - How do nephrologists in haemodialysis units consider the symptom of itch? Results
      of a survey in Germany.
AB  - BACKGROUND: Despite advances in dialysis treatment of end-stage renal disease,
      pruritus remains a widespread and distressing concomitant of chronic renal
      failure. The prevalence of uraemic pruritus (UP) across countries ranges from 10
      to 77%. Data from the DOPPS study showed that moderate to severe UP occurs in
      >40% of patients on haemodialysis. We aimed to provide data on how common and how
      serious a problem pruritus is as perceived by nephrologists in daily
      haemodialysis practice. Method. A national cross-sectional survey in 1420
      nephrologists assessed information on the number of dialysed patients, gender
      distribution, perceived prevalence of UP, time-related aspects of UP,
      characteristics of UP and its association with dialysis and therapy of UP.
      RESULTS: Most respondents reported UP to be prevalent in 1-30% of their patients,
      and 30% reported an association between UP and dialysis. Seventy-five percent
      reported an undulating pattern. Nearly half the sample suggested a relationship
      between quality of dialysis and UP. No substantial differences in recognition and
      management of UP as a function of organizational affiliation were detected.
      CONCLUSIONS: The prevalence of UP may be underestimated by nephrologists. Large
      variation in the reported prevalence of UP and the undulating pattern of UP after
      dialysis may impede the recognition of UP.

PMID- 19155534
TI  - Protective effect of peroxisome proliferator-activated receptor-gamma agonists on
      activated renal proximal tubular epithelial cells in IgA nephropathy.
AB  - BACKGROUND: We have previously demonstrated a glomerulo-tubular 'crosstalk'
      operating in the pathogenesis of tubulointerstitial injury in IgA nephropathy
      (IgAN). The present study aims to explore any possible beneficial effect of a
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist in
      alleviating the tubulointerstitial inflammation in IgAN. METHODS: Human proximal
      tubular epithelial cells (PTEC) were pre-treated with increasing concentration of
      a PPAR-gamma agonist rosiglitazone or troglitazone (0-5 microM) followed by
      further incubation with the conditioned medium (IgA-HMC) collected from human
      mesangial cells (HMC) incubated with polymeric IgA isolated from IgAN patients.
      Gene expression of interleukin-6 (IL-6) and angiotensin II type 1 receptor (ATR1)
      was detected by reverse transcription-polymerase chain reaction (RT-PCR); protein
      expression of IL-6 and ATR1 was determined by ELISA and western blot,
      respectively. The mitogen-activated protein kinase extracellular signal-related
      kinase 1/2 (ERK1/2) activation was examined by western blot. RESULTS: An IgA-HMC
      conditioned medium prepared from IgAN patients increased gene expression and
      protein synthesis of IL-6 and ATR1 in PTEC when compared with a conditioned
      medium prepared from healthy controls. The upregulated gene expression and
      protein synthesis of IL-6 and ATR1 in PTEC induced by the IgA-HMC conditioned
      medium were readily attenuated following pre-treatment with a PPAR-gamma agonist,
      thiazolidinedione (TZD). The ATR1-downregulating effect exerted by the PPAR-gamma
      agonist occurred through the inhibition of ERK1/2 activation. The PPAR-gamma
      antagonist, GW9662, significantly attenuated the inhibitory action of
      rosiglitazone on the increased synthesis of IL-6 and ATR1 protein. CONCLUSION:
      Our current findings suggest that the PPAR-gamma agonist attenuates excessive
      inflammatory response in activated PTEC in IgAN through suppressing ATR1
      expression. This ATR1-downregulating effect is likely through the inhibition of
      ERK1/2 activation and is found to be PPAR-gamma dependent. TZDs may possibly be
      new therapeutic additives to established treatment regime for renin-angiotensin
      system (RAS) blockade in IgAN.

PMID- 19155535
TI  - Protein kinase C-beta inhibition attenuates the progression of nephropathy in non
      diabetic kidney disease.
AB  - BACKGROUND: Activation of protein kinase C (PKC) has been implicated in the
      pathogenesis of diabetic nephropathy where therapy targeting the beta isoform of
      this enzyme is in advanced clinical development. However, PKC-beta is also
      increased in various forms of human glomerulonephritis with several potentially
      nephrotoxic factors, other than high glucose, resulting in PKC-beta activation.
      Accordingly, we sought to examine the effects of PKC-beta inhibition in a non
      diabetic model of progressive kidney disease. METHODS: Subtotally nephrectomized
      (STNx) rats were randomly assigned to receive either the selective PKC-beta
      inhibitor, ruboxistaurin or vehicle. In addition to functional and structural
      parameters, gene expression of the podocyte slit-pore diaphragm protein, nephrin,
      was also assessed. RESULTS: STNx animals developed hypertension, proteinuria and
      reduced glomerular filtration rate (GFR) in association with marked
      glomerulosclerosis and tubulointerstitial fibrosis. Glomerular nephrin expression
      was also reduced. Without affecting blood pressure, ruboxistaurin treatment
      attenuated the impairment in GFR and reduced the extent of both
      glomerulosclerosis and tubulointerstitial fibrosis in STNx rats. In contrast,
      neither proteinuria nor the reduction in nephrin expression was improved by
      ruboxistaurin. CONCLUSIONS: These findings indicate firstly that PKC-beta
      inhibition may provide a new therapeutic strategy in non-diabetic kidney disease
      and secondly that improvement in GFR is not inextricably linked to reduction in
      proteinuria.

PMID- 19155536
TI  - Acetaminophen, aspirin and progression of advanced chronic kidney disease.
AB  - BACKGROUND: Although many studies have investigated the possible association
      between analgesic use (acetaminophen and aspirin) and the development of chronic
      kidney disease (CKD), the effect of analgesics on the progression of established
      CKD of any cause has not yet been investigated. METHODS: In this population-based
      Swedish cohort study, we investigated the decline over 5-7 years in estimated
      glomerular filtration rate (eGFR) among 801 patients with incident, advanced CKD
      (serum creatinine >3.4 mg/dL for men, >2.8 mg/dL for women for the first time)
      and with different analgesic exposures. Lifetime analgesic use and current
      regular use were ascertained through in-person interviews at inclusion while data
      on analgesic use during the follow-up was abstracted from the medical records at
      the end of the study period. A linear regression slope, based on their eGFR
      values during the follow-up, provided a summary of within-individual change. In
      the final multivariate analyses, a linear mixed effects model was implemented to
      assess the relation of analgesic use and change in eGFR over time. RESULTS: The
      progression rate for regular users of acetaminophen was slower than that for non
      regular users (regular users progressed 0.93 mL/min/1.73 m(2) per year slower
      than non-regular users; 95% CI 0.03, 1.8). For regular users of aspirin, the
      progression rate was significantly slower than that for non-regular users
      (regular users progressed 0.80 mL/min/1.73 m(2) per year slower than non-regular
      users; 95% CI 0.1, 1.5). Different levels of lifetime cumulative dose of
      acetaminophen and aspirin did not significantly affect the progression rate.
      CONCLUSION: We suggest that single substance acetaminophen and aspirin may be
      safe to use by patients with diagnosed advanced CKD stage 4-5 without an adverse
      effect on the progression rate of the disease.

PMID- 19155537
TI  - Increased indoleamine 2,3-dioxygenase (IDO) activity and elevated serum levels of
      tryptophan catabolites in patients with chronic kidney disease: a possible link
      between chronic inflammation and uraemic symptoms.
AB  - BACKGROUND: Tryptophan (Trp) is catabolized by indoleamine 2,3-dioxygenase (IDO).
      Changes in Trp metabolism and IDO activity in chronic kidney disease (CKD) have
      not been widely studied, and the impact of haemodialysis is uncertain. Here we
      investigate Trp catabolism, IDO activity and the role of inflammation in moderate
      to very severe CKD and haemodialysis. METHODS: Eighty individuals were included
      in a prospective blinded endpoint analysis. Using tandem mass spectrometry, serum
      levels of Trp, kynurenine (Kyn), kynurenic-acid (Kyna), quinolinic-acid (Quin), 5
      hydroxytryptophan (OH-Trp), serotonin (5-HT), estimated IDO activity and
      inflammatory markers were assessed in 40 CKD patients (age 57 +/- 14 years, 21
      male, creatinine 4.5 +/- 2.7, n = 17 receiving haemodialysis), and in 40 healthy
      controls (age 34 +/- 9 years, 26 male). RESULTS: Trp levels were unchanged in CKD
      (P = 0.78 versus controls). Serum levels of Kyn, Kyna and Quin increased with CKD
      severity (stages 4, 5 versus controls all P < or = 0.01). IDO activity was
      significantly induced in CKD and correlated with disease severity (stages 3-5
      versus controls, all P < or = 0.01) and inflammatory markers [high-sensitivity C
      reactive protein (hsCRP), soluble TNF-receptor-1 (sTNFR-I); both P < or = 0.03].
      IDO products (Kyn, Kyna, Quin) correlated also with hsCRP and sTNFR-I (all P < or
      = 0.04). Haemodialysis did not influence IDO activity (P = 0.26) and incompletely
      removed Kyn, Kyna, Quin, OH-Trp and 5-HT by 22, 26, 50, 44 and 34%, respectively.
      In multiple regression, IDO activity correlated with hsCRP and sTNFR-I (both P <
      or = 0.03) independent of serum creatinine, age and body weight. CONCLUSIONS: IDO
      activity and serum levels of tryptophan catabolites of the kynurenine pathway
      increase with CKD severity. In CKD, induction of IDO may primarily be a
      consequence of chronic inflammation.

PMID- 19155538
TI  - Challenges facing anticoagulation among the elderly and frail.

PMID- 19155540
TI  - Adult issues in phenylketonuria.
AB  - Phenylketonuria (PKU) is a classical example of an inherited metabolic disease,
      in which mental retardation can be prevented successfully by using a diet.
      However, in adult PKU new problems occur, such as vitamin deficiencies,
      osteoporosis and the maternal PKU syndrome. The aim of this review article is to
      provide guidelines for the clinician to understand and manage PKU in adults.

PMID- 19155541
TI  - Eosinophilic oesophagitis: an enigmatic, emerging disease.
AB  - Eosinophilic oesophagitis is a disease that has emerged in recent years. It is
      often associated with dysphagia and oesophageal food impaction in adults. The
      disease is characterised by infiltration of eosinophilic granulocytes into the
      oesophageal mucosa. This infiltrate may be responsible for the subtle peristaltic
      abnormalities that can be found in these patients. Endoscopic findings are
      usually absent or nonspecific, although a discrete circular ring pattern of the
      mucosa may be noticed. Occasionally, overt endoscopic abnormalities (such as
      exudative changes and shearing of the mucosa) can be found. The presence of at
      least 15 intraepithelial eosinophilic granulocytes per high-power field in random
      biopsies from the whole length of the oesophagus is considered to be diagnostic.
      Gastro-oesophageal reflux needs to be excluded as it may lead to eosinophilic
      infiltration as well. Adequate diagnosis is relevant for treatment and the
      prevention of unnecessary further investigations. The disease responds well to
      the ingestion of fluticasone propionate and its long-term prognosis is generally
      good. But when fluticasone is discontinued recurrent symptoms are common, and
      some cases are severe, needing treatment with systemic corticosteroids.

PMID- 19155542
TI  - Comparison of different methods to investigate postprandial lipaemia.
AB  - Postprandial hyperlipidaemia has been associated with coronary artery disease
      (CAD). We investigated which of the generally used methods to test postprandial
      lipaemia differentiated best between patients with premature CAD (50+/-4 years,
      n=20) and healthy controls. Furthermore, the effects of rosuvastatin 40 mg/day on
      postprandial parameters were assessed. Standardised oral fat-loading tests (OFLT)
      and ambulant self-measurements of daylong capillary triglycerides (TGc) were
      performed. Total responses of individual lipoproteins, plasma TG (TGp) and
      remnant-like particle cholesterol (RLP-C) were estimated as area under the curve
      (AUC). Most AUCs were highest in untreated patients and reached control levels
      after rosuvastatin. From all AUCs, RLP-C-AUC was best associated to TGp-AUC in
      untreated patients and controls (adjusted R2=0.84, beta=0.92, p.

PMID- 19155543
TI  - Colorectal adenomas in patients presenting with inflammatory bowel disease.
AB  - BACKGROUND: Adenoma is the precursor of colorectal carcinoma (CRC). Patients with
      longstanding active ulcerative colitis (UC) are at risk of developing CRC. Every
      patient with UC can also develop adenomas, which is an extra risk factor. AIM: A
      large retrospective cross-sectional study was conducted to identify patients with
      UC and polyps. MATERIAL AND METHODS: All consecutive lower intestinal endoscopies
      carried out in a period of 16 years were searched for the presence of
      inflammation and concomitant polyps. RESULTS: Inflammatory bowel disease was
      diagnosed in 1029 patients. Forty-seven (4.5%) patients had concomitant polyps.
      The patients with polyps were divided in two groups: group 1 consisted of 34
      patients in whom active inflammation was seen with coinciding polyp(s), and group
      2 consisted of 12 patients in remission, in whom polyps were detected. One
      patient had had adenomas in the past and presented with active inflammation and a
      new adenoma. In group 1, four patients had a history of active inflammation, and
      adenomas were seen in 29 patients, while seven patients showed hyperplastic
      polyps. Two patients had adenomas as well as hyperplastic polyps. In group 2 nine
      patients had adenomas and three had hyperplastic polyps. CONCLUSION: Patients
      with different phenotypic expressions of inflammatory bowel disease can have
      concomitant adenomas in the colon. Hence, it is plausible to assume that these
      patients have an increased risk of developing CRC because of adenomas.

PMID- 19155544
TI  - Disseminated Rhizopus microsporus infection in a patient on oral corticosteroid
      treatment: a case report.
AB  - A 71-year-old male with mild steroid-induced hyperglycaemia was diagnosed with a
      lethal invasive Rhizopus microsporus infection. Disseminated zygomycosis is a
      rare entity and is most frequently found in neutropenic patients with
      haematological malignancies, post-transplants or in patients on deferoxamine
      therapy. Infection is characterised by tissue infarction and necrosis due to
      angioinvasive hyphae. Culture of Zygomycetes is necessary for species
      determination but histology is a must to prove the infection. Ante-mortem
      diagnosis and culture is challenging and therefore mortality approaches 100%.
      Apart from amphotericine B, most anti-fungals have no activity against
      Zygomycetes but posaconazole might offer new possibilities as a first-line agent.
      Timely diagnosis, rapid surgery of infected tissue, correction of underlying
      disorders and correct anti-fungal therapy might be life-saving. Due to the
      increasing use of potent immunosuppression, stem cell and organ transplants and
      possibly selection for Zygomycetes by prior treatment with broad-spectrum
      antifungal therapy, the incidence of zygomycosis is rising. Therefore, clinicians
      might encounter an increasing number of zygomycosis cases in the near future.

PMID- 19155545
TI  - A diagnostic difficulty: two cases of haemophagocytic syndrome in adults.
AB  - Haemophagocytic syndrome is a rare and life-threatening disease, which often goes
      unrecognised in adults, with high mortality as a consequence. Here we present two
      adult patients who were diagnosed with haemophagocytosis of distinct underlying
      causes which, despite treatment, led to fatal outcomes. Measuring ferritin is an
      easy and cheap resource in diagnosis.

PMID- 19155547
TI  - Budd-Chiari syndrome.

PMID- 19155548
TI  - Docetaxel-induced skin toxicity.

PMID- 19155549
TI  - Progressive trichomegaly.

PMID- 19155550
TI  - A patient with prickling boils.

PMID- 19155551
TI  - Differential representation of arm movement direction in relation to cortical
      anatomy and function.
AB  - Information about arm movement direction in neuronal activity of the cerebral
      cortex can be used for movement control mediated by a brain-machine interface
      (BMI). Here we provide a topographic analysis of the information related to arm
      movement direction that can be extracted from single trials of
      electrocorticographic (ECoG) signals recorded from the human frontal and parietal
      cortex based on a precise assignment of ECoG recording channels to the subjects'
      individual cortical anatomy and function. To this aim, each electrode contact was
      identified on structural MRI scans acquired while the electrodes were implanted
      and was thus related to the brain anatomy of each patient. Cortical function was
      assessed by direct cortical electrical stimulation. We show that activity from
      the primary motor cortex, in particular from the region showing hand and arm
      motor responses upon electrical stimulation, carries most directional
      information. The premotor, posterior parietal and lateral prefrontal cortex
      contributed gradually less, but still significant information. This gradient was
      observed for decoding from movement-related potentials, and from spectral
      amplitude modulations in low frequencies and in the high gamma band. Our findings
      thus demonstrate a close topographic correlation between cortical functional
      anatomy and direction-related information in humans that might be used for brain
      machine interfacing.

PMID- 19155553
TI  - High-pressure crystal structure of the non-linear optical compound BiB(3)O(6)
      from two-dimensional powder diffraction data.
AB  - Our recently proposed method for automatic detection, calibration and evaluation
      of Debye-Scherrer ellipses using pattern-recognition techniques and advanced
      signal filtering was applied to the two-dimensional powder diffraction data of
      the non-ferroelectric, non-centrosymmetric non-linear optical (NLO) compound
      alpha-BiB(3)O(6) as a function of pressure. At ambient conditions, alpha
      BiB(3)O(6) crystallizes in the space group C2 (phase I). In the pressure range
      between P = 6.09 and 6.86 GPa, it exhibits a first-order phase transition into a
      structure with the space group C1 (P1) [phase II at P = 8.34 GPa: a = 7.4781 (6),
      b = 3.9340 (4), c = 6.2321 (6) A, alpha = 93.73 (1), beta = 102.93 (1), gamma =
      90.76 (1) degrees , and V = 178.24 (3) A(3)]. Non-linear compression behaviour
      over the entire pressure range is observed, which can be described by two Vinet
      relations in the ranges from P = 0.0 to 6.09 GPa, and from P = 6.86 to 11.6 GPa.
      The extrapolated bulk moduli of the high-pressure phases were determined to be
      K(0) = 38 (1) GPa for phase I, and K(0) = 114 (10) GPa for phase II. The crystal
      structures of both phases were refined against X-ray powder diffraction data
      measured at several pressures between 0.0 and 11.6 GPa. The structural phase
      transition of alpha-BiB(3)O(6) is mainly characterized by a reorientation of the
      [BO(3)](3-) triangles, the [BO(4)](5-) tetrahedra and the lone electron pair
      which is localized at Bi(3+), in order to optimize crystal packing.

PMID- 19155552
TI  - Goal selection versus process control in a brain-computer interface based on
      sensorimotor rhythms.
AB  - In a brain-computer interface (BCI) utilizing a process control strategy, the
      signal from the cortex is used to control the fine motor details normally handled
      by other parts of the brain. In a BCI utilizing a goal selection strategy, the
      signal from the cortex is used to determine the overall end goal of the user, and
      the BCI controls the fine motor details. A BCI based on goal selection may be an
      easier and more natural system than one based on process control. Although goal
      selection in theory may surpass process control, the two have never been directly
      compared, as we are reporting here. Eight young healthy human subjects
      participated in the present study, three trained and five naive in BCI usage.
      Scalp-recorded electroencephalograms (EEG) were used to control a computer cursor
      during five different paradigms. The paradigms were similar in their underlying
      signal processing and used the same control signal. However, three were based on
      goal selection, and two on process control. For both the trained and naive
      populations, goal selection had more hits per run, was faster, more accurate (for
      seven out of eight subjects) and had a higher information transfer rate than
      process control. Goal selection outperformed process control in every measure
      studied in the present investigation.

PMID- 19155554
TI  - Compounds with a 'stuffed' anti-bixbyite-type structure, analysed in terms of the
      Zintl-Klemm and coordination-defect concepts.
AB  - The bixbyite structure (Mn(2)O(3)) (Ia3) is often described as a distorted face
      centered cubic (f.c.c.) array of Mn atoms, with O atoms occupying 3/4 of the
      tetrahedral holes. The empty M(4) tetrahedra are centred at 16c. In anti-bixbyite
      structures (Mg(3)N(2)), cation vacancies are centred in empty N(4) tetrahedra. If
      16 hypothetical atoms were located at this site they would form the structure of
      gamma-Si. This means that anti-bixbyite structures are ideally prepared to
      accommodate Si(Ge) atoms at these holes. Several compounds (Li(3)AlN(2) and
      Li(3)ScN(2)) fully satisfy this expectation. They are really anti-bixbyites
      'stuffed' with Al(Sc). The presence of these atoms in 16c is illuminated in the
      light of the extended Zintl-Klemm concept (EZKC) [Vegas & Garcia-Baonza (2007).
      Acta Cryst. B63, 339-345], from which a compound would be the result of 'multiple
      resonance' pseudo-structures, emerging from electron transfers between any
      species pair (like or unlike atoms, cations or anions). The coordination-defect
      (CD) concept [Bevan & Martin (2008). J. Solid State Chem. 181, 2250-2259] is also
      consistent with the EZKC description of the pseudo-structures. A more profound
      insight into crystal structures is gained if one is not restricted to the
      contemplation of classical anions and cations in their conventional oxidation
      states.

PMID- 19155555
TI  - Structural study of K(x)Na(1 - x)NbO(3) (KNN) for compositions in the range x =
      0.24-0.36.
AB  - The structure of the A-site substituted perovskite K(x)Na(1 - x)NbO(3), x = 0.24
      0.36, where a phase boundary was previously reported, has been determined by high
      resolution X-ray powder and neutron powder diffraction studies. The structure of
      the x = 0.3 compound was refined in the monoclinic space group Pm at 293 K and in
      P4mm at 523 K. The Glazer tilt system of the room-temperature monoclinic phase is
      a(0)b(+)c(0), which has implications for the nature of the next symmetry change
      with composition towards pure potassium niobate. A phase-coexistence region at
      the transition between monoclinic and tetragonal phases was also identified,
      consistent with a first-order phase boundary. There is also evidence for an
      intermediate oxygen-octahedra tilted tetragonal phase.

PMID- 19155556
TI  - Polymorphism of K(2)Co(2)Mo(3)O(12): variations in the packing schemes and
      changes in molybdenum coordination under high pressure.
AB  - Within systematic studies on the K-Co-Mo-O system so-called high-temperature and
      high-pressure modifications of K2Co2Mo3O12 were found. The Birch-Murnaghan fits
      for the ambient-conditions modification alpha (Z = 4) and the high pressure phase
      II (Z = 8) lead to V0 = 1193.09 (4) A3, K =30.8 (8) GPa, K'0= 5.4 (4) and V0 =
      2170 (10) A3, K =51 (2) GPa with K'0 fixed at 4.0, respectively. The high
      pressure phase transition is denoted as pseudoreconstructive [Wiesmann et al.
      (1997). J. Solid State Chem. 132, 88-97], because some [MoO4] tetrahedra turn
      into edge-sharing pairs of [MoO5] pyramids or face-sharing pairs of [MoO6]
      octahedra. The new phases are presented and compared with the alpha phase.

PMID- 19155557
TI  - Dynamic proton disorder and the II-I structural phase transition in
      (NH(4))(3)H(SO(4))(2).
AB  - X-ray powder diffraction, differential scanning calorimetry
      (DSC)/thermogravimetry (TG) and single-crystal neutron diffraction methods were
      used to investigate triammonium hydrogen disulfate (NH(4))(3)H(SO(4))(2) (TAHS)
      in the temperature range between 293 and 493 K. The temperature-dependent X-ray
      powder diffraction measurements show a clear hysteresis of the I <-->II phase
      transition of TAHS with transition temperatures of T(up) = 412.9 (1) K on heating
      and of T(down) = 402.6 (1) K on cooling. From the existence of hysteresis and
      from the jump-like changes of the lattice parameters, the I <--> II phase
      transition of TAHS is considered to be first order. With DSC/TG measurements we
      confirmed that there is only one phase transition between 293 and 493 K. Through
      careful investigation on single crystals of TAHS using neutron diffraction, the
      correct space group (C2/c) of room-temperature TAHS-II phase was confirmed.
      Crystal structure analysis by single-crystal neutron diffraction showed a
      strongly elongated displacement ellipsoid of the proton which lies in the middle
      of the (SO(4))H(SO(4)) dimer with ?bar 1 local symmetry. The protons of the NH(4)
      groups also show strongly enlarged anisotropic mean-square displacements. These
      findings are interpreted in terms of a characteristic proton disorder in the TAHS
      II phase.

PMID- 19155559
TI  - Planar packing of tetrachlorodicyanobenzenes. II.
AB  - Equimolar mixtures of ortho- and meta-, or ortho- and para-, or meta- and para
      tetrachlorodicyanobenzene, C(6)Cl(4)(CN)(2), form structures with disordered
      layers containing both kinds of molecules in rhombohedral or pseudo-rhombohedral
      cells. These structures are similar to the structure of the rhombohedral form of
      the meta isomer. The guiding force appears to be an intermolecular synthon, in
      which a nitrile group in one molecule interacts with Cl atoms in two adjacent
      molecules with N...Cl distances of approximately 3.1 A.

PMID- 19155558
TI  - Crystallochemical formula as a tool for describing metal-ligand complexes - a
      pyridine-2,6-dicarboxylate example.
AB  - Compounds (299) containing 494 symmetrically independent pyridine-2,6
      dicarboxylate moieties have been investigated. Among them the structures of
      Na(3)[Nd(Pydc)(3)].14H(2)O and Na(3)[Er(Pydc)(3)].11.5H(2)O, where H(2)Pydc is
      pyridine-2,6-dicarboxylic acid, were determined by single-crystal X-ray
      diffraction, while the others were taken from the Cambridge Structural Database.
      The characteristics of any complex by means of the ;method of crystallochemical
      analysis' are described, and the coordination types of all the Pydc ions and
      crystallochemical formulae of all the compounds were determined. Although the ion
      can act as a mono-, bi-, tri-, tetra- and pentadentate ligand, 96% of Pydc ions
      are coordinated to the central A atom in the tridentate-chelating mode. The
      dependence of the denticity and geometry of pyridine-2,6-dicarboxylate, as well
      as of the composition of Pydc-containing complexes, was studied as a function of
      the nature of the A atom, the molar ratio Pydc:A and the presence of neutral or
      acidic ligands in the reaction mixture.

PMID- 19155560
TI  - Following an isosymmetric phase transition by changes in bond lengths and
      anisotropic displacement parameters: the case of meta-carboxyphenylammonium
      phosphite.
AB  - Crystal structure studies in the 100-345 K temperature range were performed to
      relate the molecular structure changes of meta-carboxyphenylammonium phosphite (m
      CPAMP) to its first-order phase transition at T(c) = 246 (2) K. Thermal
      displacement parameters and most bond distances show an abrupt jump at the
      transition. Such a structural change is related to collective effects leading to
      competition between intra- and intermolecular interactions.

PMID- 19155561
TI  - Persistent hydrogen bonding in polymorphic crystal structures.
AB  - The significance of hydrogen bonding and its variability in polymorphic crystal
      structures is explored using new automated structural analysis methods. The
      concept of a chemically equivalent hydrogen bond is defined, which may be
      identified in pairs of structures, revealing those types of bonds that may
      persist, or not, in moving from one polymorphic form to another. Their frequency
      and nature are investigated in 882 polymorphic structures from the Cambridge
      Structural Database. A new method to compare conformations of equivalent
      molecules is introduced and applied to derive distinct subsets of conformational
      and packing polymorphs. The roles of chemical functionality and hydrogen-bond
      geometry in persistent interactions are systematically explored. Detailed
      structural comparisons reveal a large majority of persistent hydrogen bonds that
      are energetically crucial to structural stability.

PMID- 19155562
TI  - Probing the shapes of chiral bis-(o-naphthalimidobenzoyl) systems using X-ray and
      circular dichroism methods.
AB  - CD (circular dichroism) and X-ray investigations have been carried out in order
      to identify the prevalent conformations and define the forces that determine the
      molecular and supramolecular organization of the alkyl-bridged bichromophoric
      [NAB, ortho-(1,8-naphthalimido)benzoyl] units, each consisting of the benzoyl
      substituted in the ortho position with the 1,8-naphthalimide group. The results
      reveal that NAB bichromophores incorporated into the same molecule exist in a
      variety of conformation/helicity combinations. The molecular structures are
      largely stabilized by local 1,3-CH/CO dipole-dipole interactions, while the
      crystal packing besides dispersive H...H interactions is mostly governed by
      multiple C-H...O(=C) and C-H...pi interactions. The relatively small contribution
      of pi...pi interactions comes from a pairwise off-face stacking between
      naphthalimide rings or from pairwise carbonyl...pi interactions. All these types
      of intermolecular interactions have been summarized quantitatively by means of a
      Hirshfeld surface analysis.

PMID- 19155563
TI  - On the optimization of bond-valence parameters: artifacts conceal chemical
      effects.
AB  - We recently proposed that calculated bond-valence sums, BVS, represent a non
      integer structural valence, 'structV', rather than the integer-value
      stoichiometric valence, stoichV. Therefore, the usual attempts to 'optimize' bond
      valence parameters r0 and b by adjusting them to stoichV are based on the false
      assumption that numerical values of structV and stoichV are always equal. Bond
      valence calculations for several compounds with stereoactive cations SnII,
      SbIIIand BiIII reveal the balanced distribution of the bonding power structV
      between atoms of each structure.

PMID- 19155564
TI  - Alternative presentation of the Brown-Wu bond-valence parameters for some s(2)
      cation/O(2-) ion pairs.
AB  - Using the least-squares refinement procedure, high-performance Brown-Wu bond
      valence parameters, r(0) and n, reported for the Sn(2+)/O(2-), Sb(3+)/O(2-),
      Te(4+)/O(2-) and I(5+)/O(2-) ion pairs have been converted into the commonly used
      bond-valence parameters, r(0) and b. The r(0) and b values obtained can be
      recommended as a replacement for the conventional bond-valence parameters based
      on the 'universal constant' b = 0.37 A.

PMID- 19155566
TI  - Internal ultrastructure of human chromosomes.
AB  - By preparing metaphase chromosome spreads on Aclar (polychlorotrifluoroethylene
      fluoropolymer) film and incorporating a conventional karyotyping system, it was
      possible to observe the internal ultrastructure of individual chromosomes with
      known karyotype by means of transmission electron microscopy. Essentially, all 46
      chromosomes per human cell could be examined. Application of this method to
      chromosome research may provide comprehensive information on ultrastructural
      morphology of chromosomes from various cell types and on the fine structure of
      different chromosomal regions in relation to function.

PMID- 19155567
TI  - Late effects of childhood cancer: life-threatening issues.
AB  - Improvements in therapies for childhood cancers have increased the number of
      survivors. However, with this prolonged survival, the late effects of disease and
      anti-cancer therapy are becoming increasingly important. Approximately two-thirds
      of survivors of childhood cancer will have at least one late effect, and about
      one-third will have a late effect that is severe or life-threatening. A second
      neoplasm is one of the most severe late effects in survivors of childhood cancer.
      Compared with normal populations, persons with a history of childhood cancer have
      a 10- to 20-fold greater risk of a second malignant neoplasm. Patients who have
      undergone radiation therapy or been given specific chemotherapeutic agents and
      patients with a known genetic predisposition to malignancy have been shown to be
      at higher risk for a second malignant neoplasm. Cardiac problems are another
      serious late effect for survivors of childhood cancer. Anthracycline-induced
      cardiotoxicities are common in these patients. A cumulative dose of anthracycline
      greater than 300 mg/m2 is associated with an 11-fold higher risk of clinical
      heart failure compared with a cumulative dose of less than 300 mg/m2. Serial
      monitoring of cardiac functioning in children receiving anthracycline allows
      early identification of cardiac damage. One cardioprotectant (dexrazoxane) has
      proven effective in adult patients, but larger trials are needed to determine its
      efficacy in children. It is important to recognize that it may not be best to
      categorize surviving patients by primary diagnosis. Instead, strategies for
      surveillance of survivors should be based on the treatment each patient received.

PMID- 19155568
TI  - Experimental pancreatic cancer model using PGHAM-1 cells: characteristics and
      experimental therapeutic trials.
AB  - We developed short-term pancreatic cancer models in hamsters using PGHAM-1 cells
      and examined the utility of the models for research on metastasis and for
      therapeutic trials. With 3 PGHAM-1 models, including 1) primary pancreatic cancer
      and simultaneous liver metastasis by intrapancreatic transplantation, 2) liver
      metastasis alone by intrasplenic transplantation, 3) peritoneal dissemination by
      intraperitoneal transplantation, within 21 days after inoculation, we studied the
      specific characteristics of metastases and the effects of several antiangiogenic
      substances on primary and metastatic pancreatic tumors. Several experiments
      showed that vascular endotherial growth factor and anatomical characteristics
      were important factors for metastasis. In therapeutic experiments, the incidence,
      size, diameter, microvessel density, and apoptotic index of the tumors were
      preferably influenced by the antiangiogenic substances. In addition, PGHAM-1-Luc,
      which is luciferase-positive PGHAM-1 cell line, was newly developed and is
      expected to be a useful new animal model. These models would be suitable for the
      study of pathogenesis of pancreatic cancer and its metastasis and for preclinical
      trials of chemotherapeutic agents, such as antiangiogenic substances.

PMID- 19155569
TI  - An analysis of factors that influence the duration of suction drainage in breast
      cancer surgery.
AB  - BACKGROUND: The duration of suction drainage in patients undergoing breast cancer
      surgery is difficult to predict. The uncertainty this poses may complicate the
      development of a clinical pathway for patients with breast cancer. In this study
      we attempted to identify factors that may influence the duration of suction
      drainage in patients undergoing breast cancer surgery. METHODS: We examined the
      relationships between the duration of suction drainage and several clinical
      factors including type of drainage tube in 60 patients with primary breast cancer
      who underwent surgical resection at the Nippon Medical School Hospital in 2004
      and 2005. The drainage tubes were removed 1 day after the daily drainage volume
      had decreased to less than 50 mL or on the seventh postoperative day in patients
      in whom such a decrease did not occur. All patients were discharged from the
      hospital 1 or 2 days after the drains were removed. RESULTS: Seroma was observed
      in all patients. No complications associated with the drainage were observed. The
      median duration of drainage was 4.5 days, and the range was 2 to 7 days.
      Univariate analyses revealed significant relationships between the duration of
      drainage and the following 5 factors: patient age at surgery, body mass index,
      intraoperative blood loss, operation time, and type of surgery (total breast
      resection or partial breast resection). Univariate and multivariate analyses
      showed no significant statistical associations between the duration of drainage
      and the other factors, including the type of drainage tube. CONCLUSION: None of
      the factors examined was strongly associated with the duration of drainage. This
      study has shown that any type of drainage tube can be used in breast cancer
      surgery, in regards to the duration of drainage, and that patient discharge 1 or
      2 days after drainage tube removal is appropriate.

PMID- 19155570
TI  - A case of abdominal aortic injury caused by a traffic accident.
AB  - A 30-year-old man was injured when the large motorcycle he was riding crashed
      into a power pole. Upon arrival at our institution, the patient complained of
      abdominal pain; blood pressure at admission was 160/70 mmHg, and the heart rate
      was 112 bpm. Abdominal ultrasonography showed a small collection of fluid in
      Morrison's pouch. A chest X-ray film showed a right rib fracture. Multidetector
      computed tomography (MD-CT) revealed pleural effusion, a hepatic lesion, and a
      dissection of the abdominal aorta distal to the renal artery. Because of the
      complicated intraluminal injuries, the insertion of a stent graft was difficult.
      On the 34th day after injury, elective surgery was performed. Because dissection
      of the lumen was observed, the vessel was replaced with an artificial graft.
      Medial degeneration of the aorta wall was not observed upon pathological
      examination, and no degenerative disorders have occurred. The postoperative
      progress was favorable, and the patient was discharged from hospital.

PMID- 19155571
TI  - A case of headache attributed to otitis media chronica cholesteatomatica with
      cerebral sigmoid sinus thrombosis.
AB  - Otitis media chronica cholesteatomatica with cerebral sigmoid sinus thrombosis is
      an important differential diagnosis in the evaluation of headache. We describe a
      31-year-old Filipino man with chief complaints of headache, otalgia, vomiting,
      and vertigo, and no significant past medical history. Two years before admission
      he stuffed tissues into the right external auditory canal because of a noise in
      the street on the night of the New Years festival and sometimes had right ear
      discharge. One month before admission he had a right occipital headache with
      right otalgia and fever. One day before admission he vomited. Vertigo developed
      on the day of admission. On physical examination at admission, the patient was
      somnolent and had a body temperature of 36.9 degrees C, and meningeal signs were
      obvious. Magnetic resonance of the brain revealed right otitis media chronica
      cholesteatomatica and right cerebral sigmoid sinus thrombosis. Computed
      tomography of the skull base revealed that the tympanic cavity and mastoid air
      cells were filled with a mass of soft-tissue density invading toward the sigmoid
      sinus. Cerebrospinal fluid examination showed a cell count of 32/3 mm3. The
      patients level of consciousness and symptoms improved after administration of
      ampicillin and ceftriaxone sodium. A diagnosis of "headache attributed to
      disorder of ears," with The International Classification of Headache Disorders,
      2nd edition (ICHD-II) code 11.4, was made on the basis of symptoms and imaging
      findings. Otitis media chronica cholesteatomatica had invaded toward the sigmoid
      sinus and was thought to be the cause of cerebral sigmoid sinus thrombosis and
      meningitis. Six weeks after admission the patient underwent mastoidectomy and
      tympanoplasty to cure the cholesteatoma and prevent recurrence of inflammation.
      The postoperative progress was satisfactory. In cases of headache with otalgia,
      "headache attributed to disorder of ears" should be considered.

PMID- 19155572
TI  - Transient uptake of thallium-201 into a cerebral infarction: a case report.
AB  - We describe a 51-year-old woman with a cerebral infarction that showed transient
      accumulation of thallium-201. On admission, this lesion was well-enhanced by
      gadolinium injection and gradually expanded, mimicking a malignant brain tumor. A
      cerebral angiogram, however, did not indicate the presence of a malignant brain
      tumor. Ethyl cysteinate dimer single photon computerized tomography showed
      perfusion defects throughout hospitalization. The final diagnosis of cerebral
      infarction was established by pathological examination. Six months after onset,
      the enhancement by gadolinium and the expansion of the lesion disappeared. A
      cerebral infarction showing transient uptake of thallium-201, and lesion
      expansion is indicative of a lesion in the liquefaction stage that might mimic a
      malignant tumor. Although thallium-201 scintigrams are useful for the
      differential diagnosis of radiation necrosis and recurrent brain tumor, the
      findings in this patient should alert clinicians to the differential diagnosis of
      intracerebral expansive lesions.

PMID- 19155573
TI  - A case of asymptomatic cystitis glandularis found incidentally with
      ultrasonography at a private clinic.
AB  - A 46-year-old man was transferred to our hospital because of a bladder mass. The
      mass could not be distinguished from a primary bladder tumor or a tumor invading
      from another organ with computed tomography, magnetic resonance, or cystoscopic
      examination. Transurethral resection of the mass was performed, and the
      pathological diagnosis was typical cystitis glandularis. The patient has been
      followed up with cytologic examination and ultrasonography, and after 10 months
      there has been no new growth of the mass or malignant change.

PMID- 19155574
TI  - An infant with congenital nemaline myopathy and hypertrophic cardiomyopathy.
AB  - We describe an infant with nemaline myopathy accompanied by hypertrophic
      cardiomyopathy. The patient required long-term, intermittent positive-pressure
      ventilation after birth owing to muscle weakness, and cardiac failure developed
      during infancy. We diagnosed hypertrophic cardiomyopathy with outflow tract
      obstruction, and treated the heart failure with beta-adrenergic and angiotensin
      II receptor blockers. We discuss the prognosis of nemaline myopathy combined with
      hypertrophic cardiomyopathy.

PMID- 19155575
TI  - Basaloid squamous cell carcinoma of the esophagus: report of two cases.
AB  - Basaloid squamous cell carcinoma is an uncommon malignancy of the esophagus. We
      present two cases of basaloid squamous carcinoma of the esophagus. Both tumors
      histologically consisted of solid cell nests and displayed focal immunoreactivity
      for type IV collagen. The nests comprised pseudoglandular structures containing
      myxoid matrix. Transthoracic esophagectomy with lymph node dissection was
      performed in both patients. The patients had uneventful postoperative courses.
      One patient showed no evidence of recurrence or metastasis in the 6-month
      postoperative period, and the other patient died of lung metastasis 28 months
      after the primary treatment.

PMID- 19155576
TI  - A training session in a clinical simulation laboratory for the acquisition of
      clinical skills by newly-recruited medical interns.

PMID- 19155577
TI  - Treatment of upper eyelid dermatochalasis by resection of excess skin at the
      inferior margin of the eyebrow.

PMID- 19155578
TI  - Transport of high concentration of thiamin, riboflavin and pyridoxine across
      intestinal epithelial cells Caco-2.
AB  - In this study, we examined the intestinal uptake of thiamin (vitamin B(1)),
      riboflavin (vitamin B(2)) and pyridoxine (vitamin B(6)) administered at high
      concentration using intestinal epithelial Caco-2 cells as an in vitro model of
      drugs and food absorption. The effect of vitamin concentration, culture age,
      transport direction and incubation temperature on vitamin transport was
      determined. The vitamin transport was expressed as an apparent permeability
      coefficient and changes in cumulative fraction transported across epithelial
      membrane in time. It was found that transepithelial transport of these vitamins
      is dependent on the experimental factors. At low concentrations an active
      transport mechanism was observed, whereas at high vitamin concentration a passive
      transport dominated. At high vitamin concentration the transepithelial flux of
      vitamins in both directions was similar, which proves the mechanism of passive
      transport.

PMID- 19155579
TI  - Endemic goiter in Semirom; there is no difference in vitamin A status between
      goitrous and nongoitrous children.
AB  - BACKGROUND: Despite long-standing iodine supplementation in Iran, the prevalence
      of goiter remains high in some areas. This suggests other nutritional
      deficiencies may be considered as responsible factors for goiter persistence. In
      the present study we investigated the possible role of vitamin A deficiency (VAD)
      and low vitamin A status in the etiology of endemic goiter in Semirom, Iran.
      MATERIALS AND METHODS: In this cross-sectional study, 1,828 students from 108
      primary schools of urban and rural areas of Semirom were selected by multistage
      random cluster sampling. Thyroid size was estimated in each child by inspection
      and palpation. Urinary iodine concentration (UIC) and serum retinol (SR) were
      measured. RESULTS: Overall, 36.7% of schoolchildren had goiter. The median UIC
      was 18.5 microg/dL. The mean+/-SD of SR in goitrous and nongoitrous children was
      38.84+/- 10.98 and 39.17+/-10.85 microg/dL respectively (p=0.82). There were two
      children with VAD (SR less than 20 microg/dL); one in the goitrous and one in the
      nongoitrous group. The prevalence of subjects with low vitamin A status (SR less
      than 30 microg/dL) in the goitrous and nongoitrous groups was 26.2 and 21.5%
      respectively (p=0.42). CONCLUSION: Goiter is still a public health problem in
      this region. Iodine deficiency, VAD or low vitamin A status is not among the
      contributors of goiter persistence in schoolchildren of Semirom. The role of
      other micronutrient deficiencies or goitrogens should be investigated.

PMID- 19155580
TI  - Effect of dietary soy protein on tumor necrosis factor productivity in
      macrophages from nephritic and hepatoma-bearing rats.
AB  - The present study investigated the effect of dietary soy protein isolate (SPI) on
      tumor necrosis factor-alpha (TNF) productivity in peritoneal macrophages from
      nephritic and hepatoma-bearing rats. Dietary SPI significantly inhibited the
      elevated production of TNF by lipopolysaccharide-stimulated macrophages in
      nephritic and hepatoma-bearing rats compared with dietary casein, while it
      exerted no influence on the TNF productivity in normal rats. Removal of the minor
      components contained in SPI by ethanol extraction could significantly or
      partially restore the reduced TNF production caused by SPI in nephritic and
      hepatoma-bearing rats, respectively. These results suggest that dietary SPI could
      suppress the enhanced productivity of TNF associated with the progression of
      nephritis and hepatoma, and some factors existing in the ethanol extract of SPI
      are suggested to be involved in suppressing TNF productivity by macrophages.

PMID- 19155581
TI  - Effects of vitamin A, vitamin A plus iron and multiple micronutrient-fortified
      seasoning powder on preschool children in a suburb of Chongqing, China.
AB  - Preschool children in developing countries are likely to have multiple,
      concurrent micronutrient deficiencies. This study was designed to evaluate the
      effectiveness of different combinations of nutritional fortified diet to improve
      the blood levels of iron, vitamin A and other essential micronutrients in the
      preschool population of Banan District of Chongqing, China. From December 2005 to
      June 2006, a total of 226 2-6 y old preschool children were recruited from three
      nurseries in the area, and they were randomly assigned to three different
      fortified diet groups for 6 mo. Group I was fortified with vitamin A; groups II
      and III were fortified with vitamin A plus iron and vitamin A plus iron,
      thiamine, riboflavin, folic acid, niacinamide, zinc and calcium, respectively.
      Subjects' weight and height were measured for assessing the children's growth and
      development. Blood samples were taken at the beginning and the end of the 6-mo
      study period for measuring serum levels of micronutrients. Group III with the
      multiple micronutrient fortified diet was the most effective to improve the serum
      level of retinol from [media (P25, P75): 1.06 (0.89, 1.32)] micromol/L to 1.29
      (1.04, 1.39) micromol/L (p<0.05) and retinol binding protein from 17.0 (12.6,
      25.6) mg/L to 31.6 (24.4, 44.0) mg/L (p<0.05) and to mobilize the stored iron in
      the liver (p<0.05). In addition, the three groups' hemoglobin levels were
      elevated from 117.0 (109.0, 124.1) g/L, 114.0 (109.2, 119.7) g/L and 115.0
      (109.5, 122.7) g/L to 125.7 (119.2, 133.1) g/L, 126.5 (122.2, 135.9) g/L and
      125.1 (119.8, 131.6) g/L over the 6 mo of intervention period, but there were no
      difference among the three groups (p>0.05). Nevertheless, unexpected results were
      obtained when comparing the effects on growth status among the different
      supplement groups. Our study has demonstrated that a multiple micronutrient
      fortified diet for 6 mo is more effective to improve the levels of hemoglobin,
      serum retinol, and RBP as well as to facilitate the mobilization of iron storage
      in preschool children.

PMID- 19155582
TI  - Cholesterol lowering effect of sulfur-containing amino acids added to a soybean
      protein diet in rats.
AB  - The cholesterol-lowering action of soybean protein was studied with rats from the
      aspect of sulfur-containing amino acids using casein as a counterpart. Weanling
      rats were fed for 3 wk on a soybean protein isolate (SPI) or casein diet. Serum
      cholesterol levels did not differ between the two diet groups, but were lowered
      by supplementing methionine to a 10% SPI diet or cystine to an amino acid mixture
      diet, equivalent to a 10% SPI or to a 20% SPI diet. By adding methionine or
      cystine to a 10% SPI diet, cholesterol 7alpha-hydroxylase activity was elevated
      concomitantly with elevated hepatic glutathione (GSH) level, while hydroxyl
      methyl-glutalyl coenzyme A reductase activity was reduced by methionine,
      regardless of GSH levels. Excretion of fecal steroid was not significantly
      changed by addition of either amino acid, as expressed per body weight. These
      results indicate that the relative amount of methionine and cystine in a diet
      affected cholesterol metabolizing enzyme activity in a way not parallel to GSH
      concentration.

PMID- 19155583
TI  - Relationship of low serum selenium to anemia among primary school children living
      in rural Vietnam.
AB  - A cross-sectional study of 292 primary school children was conducted in rural
      Vietnam to investigate the relationship among micronutrient deficiencies, and
      other risk factors for anemia. Serum levels of iron, copper, zinc, selenium and
      magnesium were determined by inductively coupled plasma mass spectrometry and
      that of retinol by high performance liquid chromatography. Hemoglobin
      concentration in whole blood was measured by the cyanmethemoglobin method. The
      incidence of low serum zinc, selenium, magnesium, and copper in the children was
      91.4, 75.6, 59.5, and 8.6%, respectively. Forty-five percent of the children were
      anemic and 11.3% suffered from vitamin A deficiency. A parameter significant
      associated with anemia was low serum selenium and vice versa (OR 1.85, 95% CI
      1.06-3.24, p<0.05). Other factors associated with anemia were serum retinol <1.05
      micromol/L (OR 2.05, 95% CI 1.25-3.36, p<0.01), and age in years (OR 1.59, 95% CI
      1.16-2.18, p<0.01). The study showed that low selenium is associated with anemia
      among school children in Vietnam. Interventions are required to gain insight into
      the potential role of selenium on prevention and control of anemia.

PMID- 19155584
TI  - The effects of endotoxin on plasma free amino acid concentrations in rats.
AB  - We examined the effects of lipopolysaccharide (LPS) injection on body temperature
      and plasma free amino acid concentrations in rats. A catheter was placed in the
      jugular vein of the rats in order to draw blood from and to inject LPS into awake
      animals. On the day of the experiment, body temperature was recorded during the
      experiment (330 min) and blood was drawn before and at several time points after
      injection of LPS (10 microg/kg body weight). Body temperature in LPS-treated rats
      began to rise approximately 30 min after injection with a peak at 120 min, and
      afterward remained approximately 1 degree C higher than that in control rats
      through the end of the experiment. Concentrations of many plasma free amino acids
      were decreased by LPS treatment, with a nadir at approximately 120 min, and then
      were increased to the level of or over the control. It appears that
      thermoregulatory responses induced by LPS treatment may be related to alterations
      in plasma free amino acid concentrations. Effects of LPS treatment on the
      dynamics of plasma free branched-chain amino acid (BCAA) concentrations in rats
      with peroral or intravenous administration of BCAAs were also examined. The
      results showed that the rise in plasma BCAA concentrations after peroral BCAA
      administration was significantly suppressed by LPS treatment, but the dynamics of
      plasma BCAAs after intravenous administration was not affected by LPS, suggesting
      that LPS treatment inhibited the intestinal absorption of BCAAs into the
      circulation. These results suggest that the availability of administered BCAAs to
      the body tissues during sepsis is higher following parenteral than peroral
      administration.

PMID- 19155585
TI  - Enhancement of myofibrillar proteolysis following infusion of amino acid mixture
      correlates positively with elevation of core body temperature in rats.
AB  - Administration of an amino acid (AA) mixture stimulates muscle protein synthesis
      and elevates core body temperature (T(b)), as characteristically found under
      anesthetic conditions. We tested the hypothesis that not only AA given, but also
      AA produced by degradation of endogenous muscular protein are provided for muscle
      protein synthesis, which is further reflected in T(b) modifications. Rats were
      intravenously administered an AA mixture or saline in combination with the
      anesthetic propofol or lipid emulsion. We measured plasma 3-methylhistidine
      (MeHis) concentrations as an index of myofibrillar protein degradation, rectal
      temperature and mRNA expression of atrogin-1, MuRF-1 and ubiquitin in
      gastrocnemius and soleus muscles of rats following 3 h infusion of test
      solutions. T(b) did not differ significantly between conscious groups, but was
      higher in the AA group than in the saline group among anesthetized rats. Plasma
      MeHis concentrations were higher in the AA group than in the saline group under
      both conditions. Plasma MeHis levels correlated positively with T(b) of rats
      under both conditions. AA administration decreased mRNA levels of atrogin-1 and
      ubiquitin in gastrocnemius muscle and all mRNA levels in soleus muscle. These
      results suggest that AA administration enhances myofibrillar protein degradation
      and that the change is a determinant of T(b) modification by AA administration.
      However, the mechanisms underlying AA administration-associated enhancement of
      myofibrillar proteolysis remains yet to be determined.

PMID- 19155586
TI  - Iron, zinc, manganese and copper intakes in Japanese children aged 3 to 5 years.
AB  - This study aimed to measure and evaluate the intakes for the four trace elements
      of Fe, Zn, Mn, and Cu in 3- to 5-y-old Japanese preschool children. The study
      group consisted of a total of 90 3- to 5-y-old children living in Yokkaichi, Mie,
      Japan. Diet samples were collected by the duplicate-portion technique on 3 d at
      three different seasons between summer in 1999 and winter in 2000. The medians of
      annual mean daily intakes (25th-75th percentile) of Fe, Zn, Mn, and Cu in the 3-
      to 5-y-old children were 3.1 mg (2.4 to 3.6), 4.0 mg (3.4 to 4.7), 1.3 mg (1.1 to
      1.6), and 0.45 mg (0.35 to 0.56), respectively. The annual mean value of the
      total daily diet intake had significant correlations with the Fe, Zn, Mn and Cu
      intakes (Spearman's r=0.55, 0.67, 0.58, and 0.55, respectively; p<0.001 for all).
      There were significant correlations between each mineral intake. The Zn and Mn
      intakes had differences among ages (p=0.003 and 0.005, respectively) and the Zn
      intake significantly differed between boys and girls (p=0.031). The proportion of
      subjects whose Mn intake was the AI or less was 82%, and the proportions of
      subjects whose Fe, Zn, and Cu intakes were the estimated average requirements
      (EARs) or less were 72, 83, and 13%, respectively. Many Japanese children are
      deficient in Fe and Zn compared with the dietary reference intakes (DRIs).
      However, data in a balance study examining intakes and excretion of trace
      minerals are insufficient in children and DRIs for trace elements may change in
      future.

PMID- 19155587
TI  - Choline deprivation induces hyperhomocysteinemia in rats fed low methionine
      diets.
AB  - To clarify the relationship between dietary choline level and plasma homocysteine
      concentration, the effects of choline deprivation on plasma homocysteine
      concentration and related variables were investigated in rats fed a standard
      (25%) casein (25C) diet or standard soybean protein (25S) diet. Using the 25S
      diet, the time-dependent effect of choline deprivation and the comparative
      effects of three kinds of lipotropes were also investigated. Feeding rats with
      the choline-deprived 25S diet for 10 d significantly increased plasma total
      homocysteine concentration to a level 2.68-times higher than that of the control
      group, whereas choline deprivation had no effect in rats fed the 25C diet.
      Increases in hepatic S-adenosylhomocysteine and homocysteine concentrations,
      decreases in hepatic betaine concentration and the activity of cystathionine beta
      synthase, but not betaine-homocysteine S-methyltransferase, and fatty liver also
      occurred in rats fed the choline-deprived 25S diet. Plasma homocysteine
      concentration increased when rats were fed the choline-deprived 25S diet for only
      3 d, and the increase persisted up to 20 d. The hyperhomocysteinemia induced by
      choline deprivation was effectively suppressed by betaine or methionine
      supplementation. Choline deprivation caused hyperhomocysteinemia also in rats fed
      a choline-deprived low (10%) casein diet. The results indicate that choline
      deprivation can easily induce prominent hyperhomocysteinemia when rats are fed
      relatively low methionine diets such as a standard soybean protein diet and low
      casein diet, possibly through the suppression of homocysteine removal by both
      remethylation and cystathionine formation. This hyperhomocysteinemia might be a
      useful model for investigating the role of betaine in the regulation of plasma
      homocysteine concentration.

PMID- 19155588
TI  - Size-based distributions of postprandial lipoproteins in lymph and serum after
      oral administration of triacylglycerol and diacylglycerol oils in rats.
AB  - Several studies in humans and rodents suggest that postprandial serum
      triglyceride (TG) levels are decreased by a single oral administration of
      diacylglycerol (DAG) oil compared with administration of control triacylglycerol
      (TAG) oil. To gain further insight into the mechanisms underlying the metabolic
      properties of DAG in a postprandial state, we analyzed the size-based
      distributions of postprandial lipoproteins in the lymph and serum using gel
      filtration-based high-performance liquid chromatography. In thoracic duct lymph
      pooled for 3 h after oral administration of TAG or DAG, the size-based
      distributions of postprandial lymphatic lipoprotein-TG and -cholesterol levels
      did not differ significantly, suggesting that DAG did not affect the size of
      lipoprotein particles secreted from the small intestine. Serum lipoprotein-TG
      (60%) and -cholesterol levels (90%), however, were significantly different among
      fractions with a diameter of greater than 80 nm 1 to 2 h after the administration
      of DAG compared to TAG. In addition, there was a considerable, but
      nonsignificant, reduction in lipoprotein-TG levels (approximately 40%) in
      fractions with a diameter of 80 to 30 nm, suggesting that DAG-derived
      chylomicrons as well as DAG-derived chylomicron remnants were catabolized
      rapidly. In conclusion, dietary DAG reduced the amount of large-size lipoproteins
      in the serum, but did not affect the size distribution of lipoproteins produced
      in the small intestine. Thus, compared with TAG, dietary DAG may reduce the
      postprandial serum total TG levels.

PMID- 19155589
TI  - A water-soluble extract from Grifola frondosa, maitake mushroom, decreases lipid
      droplets in brown adipocyte tissue cells.
AB  - We investigated the effect of a water-soluble extract from Grifola frondosa, the
      maitake mushroom, on lipid droplets in brown adipocyte tissue (BAT) cells. This
      water-soluble extract inhibits the conversion of pre white adipocyte tissue (WAT)
      cells but does not inhibit that of pre BAT cells. It reduces the amount of
      accumulated triglycerides (TG) in BAT cells. The glycerol-3-phosphate
      dehydrogenase (GPDH) activities of BAT cells decreased, but the expression of
      uncoupling protein 1 (UCP1) levels increased. These results suggest that maitake
      extract inhibits TG accumulation-related energy metabolism.

PMID- 19155590
TI  - Effect of dietary docosahexaenoic acid connecting phospholipids on the lipid
      peroxidation of the brain in mice.
AB  - The effect of dietary docosahexaenoic acid (DHA, C22:6n-3) with two lipid types
      on lipid peroxidation of the brain was investigated in streptozotocin (STZ)
      induced diabetic mice. Each group of female Balb/c mice was fed a diet containing
      DHA-connecting phospholipids (DHA-PL) or DHA-connecting triacylglycerols (DHA-TG)
      for 5 wk. Safflower oil was fed as the control. The lipid peroxide level of the
      brain was significantly lower in the mice fed the DHA-PL diet when compared to
      those fed the DHA-TG and safflower oil diets, while the alpha-tocopherol level
      was significantly higher in the mice fed the DHA-PL diet than in those fed the
      DHA-TG and safflower oil diets. The DHA level of phosphatidylethanolamine in the
      brain was significantly higher in the mice fed the DHA-PL diet than in those fed
      the safflower oil diet. The dimethylacetal levels were significantly higher in
      the mice fed the DHA-PL diet than in those fed the safflower oil and DHA-TG
      diets. These results suggest that the dietary DHA-connecting phospholipids have
      an antioxidant activity on the brain lipids in mice, and the effect may be
      related to the brain plasmalogen.

PMID- 19155591
TI  - Effects of dietary medium-chain triacylglycerol on mRNA level of gluconeogenic
      enzymes in malnourished rats.
AB  - We have reported previously that dietary medium-chain triacylglycerol (MCT)
      improved serum albumin concentration and protein balance in malnourished rats. To
      clarify the mechanisms for this effect of MCT, hepatic messenger RNA levels of
      gluconeogenic enzymes, pyruvate dehydrogenase (PDH) and alanine aminotransferase
      (ALT) were measured in rats fed low-protein diets containing either MCT or
      isocaloric long-chain triacylglycerol (LCT) for 2 wk. The serum albumin
      concentration in rats fed the MCT diet was significantly higher compared with
      those fed the LCT diet. Serum free fatty acids and ketone body fraction were
      higher in rats fed MCT compared with those fed the LCT diet. The hepatic mRNA
      level of PDH was significantly lower in rats fed MCT than those fed LCT. But,
      there was no significant difference between the two groups in mRNA of
      gluconeogenic enzymes or ALT. These results suggest that ketone bodies, which are
      an alternative energy source and might spare blood glucose, increase by MCT
      feeding, and the reason for the PEM (protein-energy malnutrition)-improving
      effect of MCT is not caused by suppression of gluconeogenesis.

PMID- 19155593
TI  - [Simultaneous determination of residual veterinary drugs in livestock products
      and fish by liquid chromatography with tandem mass spectrometry].
AB  - A rapid multiresidue method was developed for determination of 98 veterinary
      drugs in livestock products and fish by LC/MS/MS. The drugs were extracted with
      methanol, and the extracted solution was diluted with water. The methanol
      concentration was adjusted to 50%, and finally the diluted solution was filtered
      through a microfiltration membrane (0.02 microm diameter pore size) prior to
      LC/MS/MS. Recoveries of 87 drugs from 4 foods (milk, egg, rainbow trout and
      cattle muscle) fortified at 0.2 microg/g were in the range of 50-150% with a
      coefficient of variation (%) of less than 20%. The values obtained by this method
      from livestock products containing antibiotics were similar to those obtained by
      the official methods. This proposed method is expected to be useful as a
      multiresidue analysis method for screening of veterinary drugs in livestock
      products and fish.

PMID- 19155592
TI  - Acute D-psicose administration decreases the glycemic responses to an oral
      maltodextrin tolerance test in normal adults.
AB  - An examination was conducted to verify D-psicose suppressed the elevation of
      blood glucose and insulin concentration in a dose-dependent manner under the
      concurrent administration of maltodextrin and D-psicose to healthy humans. Twenty
      subjects aged 20-39 y, 11 males and 9 females were recruited. A load test of oral
      maltodextrin was conducted as a randomized single blind study. The subjects took
      one of five test beverages (7.5 g D-psicose alone, 75 g maltodextrin alone, 75 g
      maltodextrin +2.5, 5 or 7.5 g D-psicose). Blood was collected before an intake
      and at 30, 60, 90 and 120 min after an intake. Intervals of administration were
      at least 1 wk. The load test with 75 g maltodextrin showed significant
      suppressions of the elevation of blood glucose and insulin concentration under
      the doses of 5 g or more D-psicose with dose dependency. An independent
      administration of 7.5 g D-psicose had no influence on blood glucose or insulin
      concentration. D-Psicose is considered efficacious in the suppression of the
      elevation of blood glucose concentration after eating in humans.

PMID- 19155594
TI  - [Multiresidue analysis of pesticides in animal and fishery products by NCI mode
      GC/MS and dual-column GC-micro ECD].
AB  - A sensitive and quantitative multiresidue method using NCI mode GC/MS and GC
      micro ECD for determining pesticides in animal and fishery products was
      established. The crude sample extract obtained by acetone-hexane extraction for
      solid samples or acetonitrile extraction for liquid samples was cleaned up with a
      GPC/SPE system. The first GPC pesticide fraction containing lipids and pigments
      was selectively collected, and loaded directly onto a graphitized carbon/PSA 2
      layered column. After the second GPC pesticide fraction was collected, the 2
      layered column was eluted with acetone-hexane (3 : 7). The combined eluate was
      subjected to NCI-SIM/Scan mode GC/MS for semi-quantification. After fractionation
      by Florisil cartridge column SPE, each fraction was subjected to dual-column GC
      micro ECD for quantification. Average recoveries (n=5) of pesticides, except for
      chlorothalonil and some others, from fortified samples ranged from 76.8% to
      107.9% with RSD values of <9.7%.

PMID- 19155595
TI  - [Analysis of chloramphenicol in propolis extract by LC/MS/MS].
AB  - A quantitative analysis method using LC/MS/MS of chloramphenicol (CAP) in
      propolis extract (ethanol extract) has been established. Extraction of CAP from
      propolis extract was performed by adding water, followed by salting-out with
      sodium chloride. Through this procedure, the wax components of propolis extract
      could be effectively removed. LC separation was performed with a reverse-phase
      column (Mightysil RP-18 GP Aqua, 2.0 mm x 150 mm, 5 microm), using 10 mmol/L of
      ammonium acetate-acetonitrile (75 : 25) as a mobile phase. The flow rate was 0.2
      mL/min. Ionization was performed by electrospray ionization (ESI) in the negative
      mode. The detection and quantification limits of CAP in propolis extract were
      0.05 and 0.15 ng/g, respectively, and the recovery rate (spiked CAP level was 0.5
      ng/g) was 111.2%. When eight samples of propolis extract products on the market
      were analyzed using this method, CAP was not detected (N.D.) in any of the
      samples.

PMID- 19155596
TI  - [Determination of diphenyl and o-phenylphenol in agricultural products by GC/MS].
AB  - A simple determination method of diphenyl (DP) and o-phenylphenol (OPP) in
      agricultural products by GC/MS was examined. DP and OPP were extracted with ethyl
      acetate in the presence of anh. sodium sulfate. After addition of n-butanol, the
      extract solution was concentrated. Clean-up was achieved by shaking with
      graphitized bulk carbon (Supelclean ENVI-Carb). Addition of polyethylene glycol
      sharpened the OPP peak on GC/MS analysis. The recoveries from 9 kinds of
      agricultural products spiked at 0.01 and 0.5 microg/g each were mostly in the
      range of 70 to 120%, except for 50% recovery of OPP from barley spiked at 0.01
      microg/g. The quantification limits (S/N > or =10) of DP and OPP were 0.0013 and
      0.005 microg/g (0.0025 and 0.01 microg/g in barley and soybean), respectively.

PMID- 19155597
TI  - [Enhancement of norovirus detection rates in oysters and other food samples by
      using bacterial treatment].
AB  - Factors such as low recovery rate and food contaminants may be responsible for
      the difficulty of detecting Norovirus (NV) by PCR in foodborne outbreaks. To
      detect NV more efficiently, we introduced a bacterial treatment, in which
      concentrated samples were incubated overnight with Klebsiella oxytoca at 35
      degrees C before RNA extraction using the standard protocol. Recovery rates of
      NVs (G I/8 or G II/13) added to food suspensions in the modified method were
      compared with those in the standard method by quantification of NV RNAs using
      real-time PCR. Recovery rates in the modified method were 8.6% for G I/8 and
      11.6% for G II/13 in 18 oyster samples and 13.9% for G I/8 and 19.6% for G II/13
      in 15 other food samples, while those in the standard method were 0.3% for G I/8
      and 0.5% for G II/13 in the oyster samples and 1.9% for G I/8 and 7.9% for G
      II/13 in the other food samples. These results indicate that the bacterial
      treatment increase the recovery of NV from foods such as oysters, suggesting that
      the modified method will be useful for NV detection in food samples.

PMID- 19155598
TI  - [Determination of sulfonamides in livestock products and seafoods by liquid
      chromatography/tandem mass spectrometry using glass bead homogenization].
AB  - A simple and rapid method using liquid chromatography coupled with tandem mass
      spectrometry (LC/MS/MS) was developed for the determination of 25 kinds of
      sulfonamides in livestock products and seafoods. The sulfonamides were extracted
      with acetonitrile by glass bead homogenization and cleaned up with a tandem
      connected ODS and basic alumina column. The quantification limits of 25 kinds of
      sulfonamides were 0.0025-0.005 microg/g. When two sulfonamides of specific
      samples were excluded, the recoveries and relative standard deviations were 70 to
      120% and less than 15%. These results show that the developed method, which
      minimizes the matrix effect, offers high precision and should be useful for the
      determination of sulfonamides in livestock products and seafoods.

PMID- 19155599
TI  - [Application of simultaneous determination method of residual veterinary drugs to
      processed foods].
AB  - To ensure the safety of processed foods, we developed a method for simultaneous
      determination of residual veterinary drugs in some processed foods. Eighty-nine
      compounds were selected for the analysis based on reports of illegal use of the
      veterinary drugs and our research information. In our LC/MS/MS system, an
      Atlantis C(18) column, which could separate a wide range of compounds, was used
      with a gradient system of 0.1% formic acid-acetonitrile containing 0.1% formic
      acid as the mobile phase. Sharp and symmetrical peaks with sufficient signal
      intensity were obtained. In this system, the recovery rates of detected
      veterinary drugs in processed foods were mostly in the range of 60-120%.
      Therefore, it is considered that this method is suitable for screening of
      residual veterinary drugs in processed foods.

PMID- 19155600
TI  - [The toxicity of starfishes, Astropecten genus, inhabiting the coast of Toyama
      Bay].
AB  - Toxicity study was conducted using an official method (mouse assay) on 77
      individual starfishes of the Astropecten genus collected in 5 sites inside Toyama
      Bay during the period from July 2002 to January 2003. Three kinds of starfishes
      were toxic, i.e., Astropecten polyacanthus, A. scoparius, and A. latespinosus
      meissner. Of A. polyacanthus. Those collected in the winter and spring were
      highly toxic, and there were regional differences in toxicity. The toxicity of A.
      latespinosus meissner, which inhibits only Himi, was less than that of A.
      polyacanthus. The toxicity of A. scoparius was weak. Toxic components were
      extracted and analyzed by LC/MS. Tetrodotoxin and related substances were
      confirmed to be present in all 3 kinds of starfishes.

PMID- 19155601
TI  - Correct diagnosis of vascular encasement and longitudinal extension of hilar
      cholangiocarcinoma by four-channel multidetector-row computed tomography.
AB  - Accurate diagnosis of local invasion of hilar cholangiocarcinomas is challenging
      due to their small size and the anatomic complexity of the hepatic hilar region.
      On the other hand, the correct diagnosis of local invasion is essential for
      assuring the possibility of curative surgery. The purpose of this study was to
      evaluate the feasibility of four-channel multidetector-row computed tomography
      (MDCT) in the assessment of vascular and bile duct involvement, by which we could
      obtain useful information for the surgical management of hilar
      cholangiocarcinoma. The subjects were 18 patients for whom the extent of tumor
      invasion was surgically and pathologically confirmed. All patients underwent
      preoperative multiphasic CT scanning by MDCT. Arterial and portal dominant phases
      were acquired using a detector configuration of 1.25 mm X 4 mm, and both axial
      and multiplanar reconstructed images were interpreted. Longitudinal extension was
      evaluated up to second-order branches. Vascular invasion is considered to be the
      degree of tumor contiguity to the hepatic arteries and portal vein and was graded
      by CT. The longitudinal extension was correctly diagnosed in 14 patients (77.8%).
      Hepatic artery invasion was correctly diagnosed in 17 patients with sensitivity
      of 100% and specificity of 90%, respectively. Portal vein invasion was correctly
      diagnosed in 47 of 51 branches with sensitivity and specificity of 92.3% and
      90.2%, respectively. Multiplanar reconstructed images contributed to the correct
      diagnosis for both vascular encasement and longitudinal tumor extension. In
      conclusion, MDCT is useful in preoperative evaluation of hilar
      cholangiocarcinoma, especially when combined with multiplanar reconstructed
      images.

PMID- 19155602
TI  - Deoxygenated hemoglobin/myoglobin kinetics of forearm muscles from rest to
      exercise in patients with chronic obstructive pulmonary disease.
AB  - Exercise capacity is frequently decreased in patients with chronic obstructive
      pulmonary disease (COPD), and muscle dysfunction is one factor in this reduction.
      Studies using (31)-phosphorus magnetic resonance spectroscopy ((31)P-MRS) have
      shown that phosphocreatine (PCr) and muscle pH (pHi) are significantly decreased
      in patients with COPD during mild exercise, suggesting the early activation of
      anaerobic glycolysis in their muscles. Thus, muscle oxygenation states during
      exercise might differ between patients with COPD and healthy individuals. We
      simultaneously measured oxygenation state and pHi in the muscles of patients with
      COPD during the transition from rest to exercise (on-transition) using near
      infrared spectroscopy (NIRS) and (31)P-MRS. Sixteen patients with COPD (aged 68.6
      +/- 7.5 years) and 7 healthy males (controls; aged 63.3 +/- 7.5 years) performed
      dynamic handgrip exercise (lifting a weight by gripping at a rate of 20 grips per
      min for 3 min). Patients were classified based on pHi data at the completion of
      exercise as having a normal (>or= 6.9; n = 8) or a low (< 6.9; n = 8) pHi. The
      deoxygenated hemoglobin/myoglobin (deoxy-Hb/Mb) in NIRS recordings remained
      constant or slightly decreased initially (time delay), then increased to reach a
      plateau. We calculated the time delay and the time constant of deoxy-Hb/Mb
      kinetics during the on-transition. The time delay was shorter in the group with a
      low pHi than in the controls. These findings might reflect a slower increase in
      O(2) delivery in patients with a low pHi, which might partly account for altered
      muscle energy metabolism.

PMID- 19155603
TI  - Decreased serum paraoxonase 1 activity and increased serum homocysteine and
      malondialdehyde levels in age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is one of the most common causes of vision
      loss. AMD has been classified into two forms: atrophic and exudative forms. The
      exudative form is associated with choroidal neovascularization of the subretinal
      macular region, resulting in a sudden loss of central vision. However, the exact
      cause of AMD remains unknown. Several risk factors have been postulated,
      including smoking, atherosclerosis, and low levels of antioxidant enzymes.
      Malondialdehyde (MDA), a lipid peroxidation product, is used as a marker of
      oxidative stress. Paraoxonase 1 (PON1) metabolizes lipid peroxides and prevents
      oxidation of low-density lipoprotein. Increased levels of homocysteine may cause
      vascular endothelial injury by releasing free radicals. The purpose of this study
      is to investigate the relationships between serum PON1 activity and the serum
      levels of homocysteine and MDA in AMD. Forty patients with exudative-type AMD
      (63.3 +/- 5 years) and 40 controls (61+/- 4 years) were assessed in a cross
      sectional study. The serum PON1 activity was significantly lower in the patients
      with AMD than that in the controls (p < 0.001). In contrast, the serum levels of
      MDA and homocysteine were significantly higher in the patients than those in the
      controls (p < 0.001, for both). In AMD patients, significant negative correlation
      was found between PON1 activity and MDA level (r = -0.493, p < 0.05) and between
      PON1 activity and homocysteine level (r = -0.557, p < 0.05). Increased serum
      homocysteine and MDA levels may be responsible for the decreased PON1 activity in
      patients with AMD.

PMID- 19155604
TI  - The nutrient formula containing eicosapentaenoic acid and docosahexaenoic acid
      benefits the fatty acid status of patients receiving long-term enteral nutrition.
AB  - Currently, various formulas with different fatty acid compositions are used for
      enteral nutrition (EN). All formulas contain various concentrations of essential
      fatty acids: linoleic acid (LA) and alpha-linolenic acid (ALA); LA is
      biotransformed into arachidonic acid (AA) and ALA into eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA) in vivo. Some formulas contain preformed EPA
      and DHA. However, the effects of the differences in the fatty acid composition on
      the fatty acid status of patients receiving long-term EN is not clear. We
      measured serum fatty acid concentrations in 50 patients with neurological
      diseases receiving long-term EN. The data were then compared retrospectively with
      reference to the fatty acid compositions of the formulas used. All of the
      patients received almost their entire nutritional intake via EN for at least 1
      year. Blood samples were obtained just before injecting the EN solution. Among
      the formulas that did not include EPA or DHA, formulas with low ALA
      concentrations were associated with low serum EPA and DHA. Conversely, the ALA
      enriched formulas with reduced LA concentrations significantly increased EPA and
      DHA levels, although the levels remained lower than the control values. With the
      formula containing EPA and DHA, the EPA and DHA levels reached control values.
      Therefore, the fatty acid composition of the EN formulas affected the fatty acid
      status of patients receiving long-term EN. Formulas containing preformed EPA and
      DHA with suitable amounts of essential fatty acids may benefit these patients.

PMID- 19155605
TI  - Differences in practice patterns and costs between small cell and non-small cell
      lung cancer patients in Japan.
AB  - Many reports exist regarding the economic evaluation of evolving chemotherapeutic
      regimens or diagnostic images for lung cancer (LC) patients. However, it is not
      clear whether clinical information, such as pathological diagnosis or cancer
      stage, should be considered as a risk adjustment in lung cancer. This study
      compared the cost and practice patterns between small cell lung carcinoma (SCLC)
      and non-small cell lung carcinoma (NSCLC) patients. 6,060 LC patients treated at
      58 academic hospitals and 14,507 at 257 community hospitals were analyzed. Study
      variables included demographic variables, comorbid status, cancer stage, use of
      imaging and surgical procedures, type of adjuvant therapy (chemotherapy,
      radiation or chemo-radiation), use of ten chemotherapeutic agents, length of stay
      (LOS), and total charges (TC; US$1 = 100 yen) in SCLC and NSCLC patients. The
      impact of pathological diagnosis on LOS and TC was investigated using
      multivariate analysis. We identified 3,571 SCLC and 16,996 NSCLC patients. The
      proportion of demographic and practice-process variables differed significantly
      between SCLC and NSCLC patients, including diagnostic imaging, adjuvant therapy
      and surgical procedures. Median LOS and TC were 20 days and US$6,015 for SCLC and
      18 days and US$6,993 for NSCLC patients, respectively (p < 0.001 for each
      variable). Regression analysis revealed that pathological diagnosis was not
      correlated with TC. Physicians should acknowledge that pathological diagnosis
      dose not accounts for any variation in cost of LC patients but that should remain
      as an indicator of appropriate care like selection of chemotherapeutic agents.

PMID- 19155606
TI  - Smoking as an independent risk factor for hypertension: a 14-year longitudinal
      study in male Japanese workers.
AB  - There have been few large longitudinal studies on the relationship between
      smoking and blood pressure and those results have been inconsistent. The aim of
      this study was to clarify the influence of smoking on the onset of hypertension.
      A 14-year longitudinal study was conducted in Japanese male workers at a steel
      company between 1991 and 2005. We adopted three different endpoints of
      observation, hypertension [systolic blood pressure (SBP) >or= 140 mmHg and
      diastolic blood pressure (DBP) >or= 90 mmHg], systolic hypertension (SBP >or= 140
      mmHg), and diastolic hypertension (DBP >or= 90 mmHg), with initiation of
      antihypertensive medication. The cohort for each endpoint (hypertension: n =
      5,512, systolic hypertension: n = 5,765, diastolic hypertension: n = 6,063) was
      selected, excluding the subjects whose blood pressure was higher than above
      criteria at their first health examination from all 8,251 workers. The strict
      criteria for hypertension resulted in exclusion of more subjects, yielding
      smaller cohort for hypertension. The association between smoking and each
      endpoint was investigated adjusting for age, body mass index, drinking, habitual
      exercise, job schedule type, hemoglobin A1c, total cholesterol, creatinine,
      aspartic aminotransferase, gamma-glutamyl transpeptidase, and uric acid by pooled
      logistic regression analyses. The significant odds ratios (and 95% confidence
      intervals) of smoking were 1.13 (1.03 to 1.23) for hypertension and 1.15 (1.05 to
      1.25) for systolic hypertension. This study revealed that smoking is
      independently related to the onset of hypertension and systolic hypertension in
      Japanese male workers. These results provide important information necessary to
      define the effect of smoking on blood pressure.

PMID- 19155607
TI  - Health related quality of life and sense of coherence in Sudanese diabetic
      subjects with lower limb amputation.
AB  - Quality of life is an important outcome measure in diabetic patients with lower
      limb amputation (LLA). The aim of this study was to investigate the influence of
      lower limb amputation on health-related quality of life (HRQOL) in Sudanese
      diabetic subjects. Additionally the Sense of Coherence scale (SOC-13) and a
      symptom check list was used in subjects with LLA. A total of 60 (M/F; 40/20)
      diabetic subjects with LLA and 60 (M/F; 23/37) diabetic reference subjects
      without LLA, were studied. For both groups HRQOL was measured using The Medical
      Outcomes Study questionnaire (MOS). Subjects with LLA had significantly poorer
      HRQOL compared to the reference group in most HRQOL domains (p < 0.0001).
      Duration of diabetes had the greatest negative impact on HRQOL in both groups,
      those with LLA (p < 0.0001), and in those without LLA (p < 0.0001), although
      subjects who were amputated earlier had poorer HRQOL than recently amputated (p <
      0.0001). Higher SOC scores were recorded in LLA patients who have greater ratings
      of positive feelings, family satisfaction and sleep in the HRQOL examination (p <
      0.0001). In conclusion, Sudanese diabetic subjects with LLA have a poor quality
      of life. The triad of diabetes duration, symptoms and amputations, has turned to
      be important risk factor for poorer HRQOL. Functional and mobility status were
      suggested to be an important determinant of HRQOL among this population. As the
      Sudanese population has coherent social relationships, this poor performance of
      the diabetic subjects will certainly increase the burden on the whole family, in
      both integrity and economical status. Nevertheless, these deep-rooted social
      interrelations together with increasing diabetes awareness have substantially
      improved the family satisfaction among our patients.

PMID- 19155608
TI  - Glucocorticoid inhibits bone regeneration after osteonecrosis of the femoral head
      in aged female rats.
AB  - Idiopathic osteonecrosis of the femoral head (ION) is a painful disease of the
      hip, the pathogenic mechanism of which is still unclear. The most common
      extraneous factor is steroid treatment. Steroids have inhibiting effects on bone
      formation and resorption. When bone regenerative treatments are indicated for ION
      patients who are exposed to steroids, we cannot ignore the effects of
      corticosteroid itself on bone healing. The aim of this study was to investigate
      the effects of glucocorticoid on bone regeneration after osteonecrosis of the
      femoral head in a rat model. Osteonecrosis was induced surgically on the left
      femoral heads of aged female rats (about 6 months old) on day 0.
      Methylprednisolone sodium succinate (MPSS) or normal saline was administrated at
      a dose of 100 mg/kg/day from day 7 to 11. Femoral heads were analyzed
      histologically. There were no pathological findings in the right femoral heads of
      the MPSS-treated and saline-treated rats, as control for the contralateral
      injury. The newly formed bone volume and the osteoclast number were significantly
      smaller in the MPSS-treated group. The normal bone marrow was regenerated in the
      saline-treated group, whereas most of the bone marrow space still contained
      fibroblast-like spindle-shaped cells in the MPSS-treated group on day 42.
      Alkaline phosphatase-positive cells were only seen in the areas around the
      regenerated bone marrow cavities. Thus, MPSS inhibits bone formation by
      suppressing osteoblast proliferation and resorption by suppressing the
      recruitment of osteoclast precursors. These findings may be useful when designing
      treatments for ION patients exposed to steroids.

PMID- 19155609
TI  - Adiponectin reduces glucotoxicity-induced apoptosis of INS-1 rat insulin
      secreting cells on a microfluidic chip.
AB  - Diabetes mellitus is a metabolic disorder characterized by elevated blood sugar
      and progressive failure of insulin-producing beta-cells. Persistent hyperglycemia
      and blood sugar fluctuation are two general phenomena in diabetic patients, and
      both of them can result in an increased frequency of beta-cell apoptosis.
      Therefore, rescuing pancreatic beta-cells from glucotoxicity-induced beta-cell
      apoptosis is increasing viewed as a promising means for curing. The aim of this
      study was to investigate whether adiponectin, an important cytokine expressed in
      adipose tissue, has a potential for the application as the antiapoptotic
      strategy. INS-1 rat insulin-secreting cell line was used in this study as a model
      of pancreatic beta-cells, because INS-1 cells show the susceptibility to
      glucotoxicity, as seen in beta-cells. INS-1 cells were cultured on a novel
      microfluidic chip with persistent perfusion and subsequently exposed to sustained
      high glucose (SHG) (25 mmol/l) or intermittent high glucose (IHG) (11.1 and 25
      mmol/l glucose alternating every 12 h) in the absence or presence of adiponectin
      for 72 h. Using this device, we showed that IHG induced more serious impairment
      in INS-1 cells than did SHG, and adiponectin partially rescued INS-1 cells from
      glucotoxicity-induced apoptosis, dysfunction and reduction of insulin gene
      expression. Simultaneously, the mRNA expression of AMP-activated protein kinase
      (AMPK), which is a signaling protein that acts to modulate glucose uptake in
      skeletal muscle, was restored in the presence of adiponectin. Based on the above
      evidence, we suggest that adiponectin could reduce glucotoxicity-induced
      apoptosis of beta-cells, at least in part, by transiently activating AMPK
      signaling pathway.

PMID- 19155610
TI  - Unhealthy maternal lifestyle leads to rapid infant weight gain: prevention of
      future chronic diseases.
AB  - Infants' rapid (catch-up) weight gain is associated with later obesity and
      chronic adult diseases. The aim of this study was to determine maternal and
      environmental factors related to rapid weight gain at one month and 18 months
      after full-term birth in Japan. Subjects were 1,524 infants and their mothers who
      visited the 18-month check-up in Niigata City between October 1, 2007 and
      September 30, 2008. An anonymous questionnaire elicited information on the
      infant's weight (at birth, 1 month, and 18 months), sex, feeding method, presence
      of food allergy, gestational age, and caregiver. Mother's information was height,
      pre-pregnancy weight, pregnancy weight gain, age at delivery, pregnancy
      toxicosis, number of daily meals during pregnancy, smoking and drinking habits.
      Some questionnaire items were obtained from a maternal and child health handbook.
      Independence of predictors for rapid weight gain (vs. slow or average weight
      gain), i.e. a score gain of 0.67 SD, during the first month and first 18 months
      was tested by multiple logistic regression analysis. In the first month, having a
      meal once or twice daily during pregnancy (P = 0.0016) and daily smoking in pre
      pregnancy (P = 0.0175) were associated with rapid weight gain. In the first 18
      months, use of daycare (P = 0.0083) and daily drinking in pre-pregnancy (P =
      0.0130) were associated with rapid weight gain. We conclude that mother's pre
      pregnancy smoking and drinking, dieting during pregnancy, and infant daycare
      attendance lead to rapid infant weight gain. Controlling these factors may
      prevent future chronic adult lifestyle-related diseases.

PMID- 19155611
TI  - Improvement in mothers' immediate care-seeking behaviors for children's danger
      signs through a community-based intervention in Lusaka, Zambia.
AB  - The large number of child deaths in developing countries is associated with
      delays in care-seeking by families, but the community-based efforts of the
      Integrated Management of Childhood Illnesses developed by WHO/UNICEF has remained
      ineffectual. To improve caregivers' ability to recognise potentially life
      threatening symptoms of major childhood illnesses, we provided education about
      the importance of danger signs and immediate care-seeking practices through a
      community-based intervention of 'the Growth Monitoring Programme Plus (GMP+)' in
      low-income areas of Lusaka, Zambia. Using repeated cross-sectional data from
      interviews, we compared attendance and non-attendance groups to assess the
      impacts of intervention on mothers' care-seeking. Of 1717 and 1546 attendance
      mothers in the baseline and the final survey, 1097 and 1035, respectively, sought
      care from a health centre after perceiving the danger signs. The proportion of
      mothers with immediate response increased from 35.7% (392/1097) to 51.5%
      (533/1035) (p < 0.01). In the final survey, the attendance mothers became more
      likely to respond immediately to the danger signs than the non-attendance mothers
      (adjusted odds ratio: 2.140, 95% confidence interval: [1.408-3.252]), and the
      higher educational level the attendance mothers had, the more likely they were to
      respond immediately to the danger signs (primary level: 2.067 [1.050-4.068],
      secondary level and above: 2.174 [1.098-4.306]). In conclusion, GMP+ with danger
      sign education can improve mothers' care-seeking for severely sick children.
      Therefore, GMP+ has the potential to reduce child death in developing countries,
      i.e., contribute to the Millennium Development Goal 4 aiming at reducing child
      mortality by two-thirds by 2015.

PMID- 19155612
TI  - Sulfadiazine partially protects the rat temporal cortex from amyloid beta peptide
      (25-35)-induced alterations of the somatostatinergic system.
AB  - The aim of this study was to elucidate whether sulfadiazine, shown to improve
      cognitive capacity in the elderly, can prevent amyloid beta peptide (Abeta) (25
      35)-induced impairment of the somatostatinergic system previously reported by our
      group in rat temporal cortex. Male Wistar rats were thus treated with
      sulfadiazine (160 mg/kg) or vehicle, via a gastric cannula, twice on the day
      prior to Abeta(25-35) treatment. On the following day and during 14 days,
      Abeta(25-35) was administered intracerebroventricularly (i.c.v.) via an osmotic
      minipump connected to a cannula implanted in the right lateral ventricle (300
      pmol/day). Sulfadiazine (80 mg/kg) or vehicle was administered once again the
      last 2 days of the Abeta(25-35) infusion. All animals were sacrificed by
      decapitation 24 h after the last sulfadiazine dose. The findings obtained reveal
      that sulfadiazine partially prevents the decrease in somatostatin (SRIH)-like
      immunoreactivity content in the temporal cortex of rats infused with Abeta(25-35)
      during 14 days. In addition, sulfadiazine blocks the Abeta(25-35)-induced
      reduction in the SRIH receptor density and in SRIH receptor subtype 2 expression.
      Sulfadiazine treatment also restored the inhibitory effect of SRIH on basal
      adenylyl cyclase activity back to control values. Altogether, the results suggest
      that sulfadiazine might have beneficial effects in the early treatment of
      Alzheimer's disease.

PMID- 19155613
TI  - Assessing the value of supportive skin care: development and validation of an
      instrument for evaluating patient-relevant benefit.
AB  - BACKGROUND: Supportive skin care for irritated and inflamed skin is one of the
      most important measures in the prevention and treatment of eczema and sensitive
      skin. OBJECTIVES: To develop and validate an instrument for the evaluation of
      patient-relevant benefit in the supportive care of irritated skin with
      nonpharmacological topical agents. METHODS: Patient-defined treatment objectives
      and benefits of supportive skin care were determined in an open survey of
      patients with irritated skin. A pilot questionnaire was constructed according to
      the Patient Benefit Index (PBI). The questionnaire was tested for feasibility and
      validity in 1,886 patients with various irritated skin conditions. RESULTS: From
      a total of 90 characteristics of basic therapy benefit, a 23-item questionnaire
      was constructed. This questionnaire ('PBI-k') proved to be feasible, reliable and
      was associated with a high level of patient acceptance in the surveillance field.
      The questionnaire showed good internal consistency, distribution characteristics
      and convergent validity with patient satisfaction. CONCLUSION: The PBI-k is the
      first specific instrument developed for the evaluation of patient-defined benefit
      in supportive skin care with nonpharmacological topical agents. Feasibility and
      psychometric properties make this questionnaire suitable for application in
      studies involving patients with irritated, sensitive skin.

PMID- 19155614
TI  - Precalcaneal congenital fibrolipomatous hamartomas: report of 3 additional cases
      and discussion of the differential diagnosis.
AB  - We report 3 cases of otherwise healthy infants with nodules on their soles. The
      nodules were present at birth or developed in early childhood. This condition has
      first been described in 1977 and was termed precalcaneal congenital
      fibrolipomatous hamartoma (PCFH). Since then the same entity has been reported
      under various denominations. The incidence of PCFH is underestimated, and it is
      important to recognize the benign nature of this disorder.

PMID- 19155615
TI  - Generalized granuloma annulare treated with methylaminolevulinate photodynamic
      therapy.
AB  - Granuloma annulare (GA) is a non-infectious granulomatous dermatosis
      characterized by annular papules and rarely nodules and plaques, arising on the
      dorsa of the hands, feet, elbows and knees; it is usually chronic and
      asymptomatic. The aetiology of GA is unknown, although many hypotheses have been
      postulated. About 10% of patients affected by GA present the generalized subtype,
      characterized by a later age of onset and a chronic course with a low tendency to
      spontaneous resolution. The widespread papular eruption develops on the trunk and
      upper or lower limbs. Generalized GA is very disfiguring because of the extensive
      dissemination of the lesions. The response to various treatments, namely topical
      and intralesional corticosteroids, topical tacrolimus, dapsone, isotretinoin,
      etretinate or hydroxychloroquine, is usually unsatisfactory. We report 3 cases
      with long-lasting generalized GA responding to methylaminolevulinate photodynamic
      therapy.

PMID- 19155616
TI  - Two observations raising questions about risk factors of cutaneous necrosis
      induced by terlipressin (Glypressin).
AB  - INTRODUCTION: Triglycyl lysine vasopressin (terlipressin, Glypressin) is a potent
      vasoconstrictive drug which became popular because of its prolonged duration of
      action, ease of administration and lower incidence of side effects. Ischemic
      complications are rare but may be life threatening. OBSERVATIONS: Case 1, a 68
      year-old man with alcoholic cirrhosis and hepatocellular carcinoma, was admitted
      due to acute functional renal failure. He was first treated for septic shock with
      intravenous catecholamines. He then developed hepatorenal syndrome and received
      terlipressin as intravenous bolus (4 mg/day). Three days later, he presented a
      diffuse purpuric and necrotic eruption with tongue ischemia. He died from
      Staphylococcus aureus infection. Case 2, a 74-year-old man with metastatic
      carcinoma, presented severe renal insufficiency. He developed sepsis and
      pseudohepatorenal syndrome, which was treated with terlipressin (0.5 mg/h) using
      an infusion pump. Four days later, he developed an isolated large erythematous
      and purpuric macular plaque of the scalp near skin metastases. The patient died a
      few weeks later from tumor progression. In both cases, skin biopsies showed
      ischemic necrosis caused by thrombosis of superficial dermal capillaries.
      CONCLUSION: These cases point to the risk of either widespread or localized
      necrosis. Although the precise incidence of these events as well as risk factors
      remain to be determined, hypovolemia, concomitant administration of vasoactive
      drugs and the mode of administration of terlipressin may influence the occurrence
      of these complications.

PMID- 19155617
TI  - Acute renal failure and its risk factors in Stevens-Johnson syndrome and toxic
      epidermal necrolysis.
AB  - BACKGROUND: Skin lesion is the most frequent manifestation of adverse drug
      reactions. Drug-induced cutaneous hypersensitivity and drug-induced acute
      interstitial nephritis might share a similar mechanism involving drug-specific T
      cells. We thus investigated the renal outcome of Stevens-Johnson syndrome (SJS)
      and toxic epidermal necrolysis (TEN), the most severe drug-induced cutaneous
      hypersensitivity, and hypothesize that skin detachment in SJS/TEN might be
      associated with acute renal failure (ARF). METHODS: 234 hospitalized patients
      were retrospectively classified into an SJS/TEN group (skin detachment) or an
      erythematous multiforme majus group (target-like exanthema alone). RESULTS: Both
      drugs and chronic kidney disease (CKD) are associated with SJS/TEN. The SJS/TEN
      group was more likely to develop ARF than the erythematous multiforme majus group
      (18.8 vs. 4.3%, p < 0.05) despite similar initial creatinine clearance. In the
      ARF patients, RIFLE-F class, dialysis and long-term dialysis were 25, 15 and 5%,
      respectively. The offending drugs in ARF were also associated with CKD.
      Hyponatremia and late hypokalemia were more frequently in the SJS/TEN group (15.6
      vs. 2.9%, 7.3 vs. 0.7%, respectively, p < 0.05). Sepsis, allopurinol,
      antibiotics, NSAIDs, CKD and hypoalbuminemia (OR: 18.8, 9.8, 10.1, 9.0, 5.3 and
      3.3, respectively, p < 0.05) were the risk factors of developing ARF. CONCLUSION:
      ARF, the need for dialysis, and late hypokalemia could be the consequences of
      SJS/TEN. Skin detachment after certain medication might implicate the associated
      ARF, especially in CKD patients.

PMID- 19155618
TI  - Angiotensin blockade prevents salt-induced injury of the renal circulation in
      spontaneously hypertensive rats.
AB  - BACKGROUND/AIMS: We hypothesized that renal damage induced by salt overload may
      be related to increased activity of the renin-angiotensin system. Thus, we
      examined the renal effects of angiotensin II receptor blockade in spontaneously
      hypertensive rats (SHR) with salt overload. Two different blockers were used to
      demonstrate that the effect depends on receptor blockade per se. METHODS: Male, 8
      week-old SHR were divided into 4 groups; the control group was given regular
      chow, the remaining 3 groups were given chow with 8% salt. In addition, the third
      group was given candesartan (10 mg/kg/day) and the fourth losartan (30
      mg/kg/day). Treatment lasted for 8 weeks. RESULTS: Compared with controls, mean
      arterial pressure increased in salt-loaded rats and was not decreased by
      candesartan or losartan. Indices of renal function including renal blood flow,
      glomerular filtration rate, and urinary protein excretion were greatly and
      adversely affected by salt overload, and they were completely restored with
      either drug. CONCLUSION: These results demonstrated that dietary salt excess
      adversely affected renal function, hemodynamics and structure. Angiotensin
      receptor blockade did not affect arterial pressure but prevented other adverse
      effects of salt overload, indicating that renal damage was not dependent on
      arterial pressure but, more likely, on another mechanism involving the renin
      angiotensin system.

PMID- 19155619
TI  - Screening for sterilizing activity of antibiotic combinations in an acid model of
      rapidly growing mycobacteria during the stationary phase of growth.
AB  - BACKGROUND: In view of the problems of correlation between the data provided by
      classical microbiological studies and clinical response, we designed an in vitro
      method to screen for the sterilizing activity of various antibiotics,
      individually or in combinations, against clinical isolates of various rapidly
      growing mycobacteria in the stationary phase. MATERIAL AND METHODS: We screened a
      large number of antibiotic combinations (4-16 microg/ml) for their sterilizing
      capacity in 26 Mycobacterium fortuitum clinical isolates, 7 Mycobacterium
      chelonae and 2 Mycobacterium abscessus clinical isolates (10(5) CFU). RESULTS:
      The best results against M. fortuitum were obtained with moxifloxacin, both on
      its own (13/26 strains) and in combination. This drug is also very active against
      M. chelonae (3/7 strains), and in combination with clarithromycin and amikacin
      exhibits sterilizing activity against all the strains studied. Combinations of
      clarithromycin with moxifloxacin or linezolid at high doses (16 microg/ml)
      exhibit activity against M. abscessus. CONCLUSIONS: The most relevant finding of
      our study is the good activity of moxifloxacin against these microorganisms in
      the stationary phase. This indicates the need to confirm these data in animal
      models or clinical trials in order to determine their true clinical importance.

PMID- 19155620
TI  - Broad spectrum antiviral fractions from the lichen Ramalina farinacea (L.) Ach.
AB  - BACKGROUND: An ethylacetate-soluble fraction (ET4) from the lichen Ramalina
      farinacea has previously been shown to inhibit the infectivity of lentiviral and
      adenoviral vectors, as well as wild-type HIV-1. We now determined the antiviral
      activity of ET4 against other wild-type viruses, including the herpes simplex
      virus type 1 (HSV-1) and the respiratory syncytial virus (RSV). METHODS: Wild
      type HIV-1, HSV-1 or RSV were pre-incubated with various concentrations of ET4
      for 30 min at 37 degrees C before adding to P4CCR5 indicator cell line (HIV-1),
      ELVIS TM indicator cell line (HSV-1) or HEp2 cell line (RSV) in 96-well
      microtitre plates. Controls contain virus alone without ET4. The anti-HIV and
      anti-HSV activities were quantified by estimating beta-galactosidase expression
      of the respective indicator cell lines while the anti-RSV activity was determined
      via an immunofluorescent technique, employing monoclonal mouse antibody against
      the P-protein of RSV. Toxicity of ET4 to cell lines was evaluated in parallel
      using either the BrdU incorporation method or the MTT method. The effect of ET4
      on the enzymatic activity of HIV-1 reverse transcriptase was also evaluated using
      a chemiluminescent reverse transcriptase assay. Bioassay-guided fractionation of
      the whole methanol extract of R. farinacea involved sequential screening of HPLC
      fractions using a vector-based assay technique. RESULTS: ET4 inhibited HSV-1 and
      RSV potently (IC(50)=6.09 and 3.65 microg/ml, respectively). Time-of-addition
      studies suggest that both entry and post-entry steps of the HIV-1 replication
      cycle and the entry step of the RSV replication cycle are targeted. Furthermore,
      ET4 inhibited HIV-1 reverse transcriptase with an IC(50) of 0.022 microg/ml.
      Bioassay-guided fractionation of ET4 led to the identification sub-fraction rfO,
      with activity against lentiviral vector and HIV-1 (RNA viruses) but not against
      HSV-1 (DNA virus) and sub-fraction rfM, with activity against HSV-1 but not
      against the lentiviral vector. CONCLUSIONS: ET4 represents a novel fraction from
      the lichen R. farinacea with broad spectrum antiviral activity against DNA
      viruses (adenovirus and HSV-1) and RNA viruses (HIV-1 and RSV). The effect
      against DNA and RNA viruses is mediated by different sub-fractions within R.
      farinacea.

PMID- 19155622
TI  - Interleukin-1alpha -889 C/T polymorphism in Turkish patients with late-onset
      Alzheimer's disease.
AB  - BACKGROUND/AIMS: The polymorphism (rs1800587) in the 5'-flanking regulatory
      region at -889 of the interleukin-1alpha gene has been shown to be associated
      with inflammatory diseases and Alzheimer's disease (AD). The aim of the current
      study is to determine whether there is an association between the promoter region
      polymorphism of the interleukin-1alpha gene and late-onset AD in a cohort of
      Turkish patients. METHODS: One hundred and four subjects with dementia of the
      Alzheimer type and 103 age-matched controls were genotyped according to the PCR
      with confronting two-pair primers method. RESULTS: Although the distribution of
      genotypes did not significantly differ (p = 0.107), the difference between
      allelic frequency was nearly significant according to a chi(2) test (p = 0.05)
      when the controls and patients were compared. CONCLUSION: Our results showed that
      there is no association between the -889 C/T transition on the interleukin-1alpha
      gene and late-onset AD in the Turkish population.

PMID- 19155621
TI  - Factors underlying caregiver stress in frontotemporal dementia and Alzheimer's
      disease.
AB  - BACKGROUND: Frontotemporal dementia (FTD) has devastating effects on patients and
      caregivers, yet the factors underlying caregiver stress are poorly understood.
      METHODS: 108 caregivers (79 = FTD, 29 = Alzheimer's disease) participated in a
      postal survey. Self-report measures of perceived stress, depression, social
      networks, as well as patient-based measures of behaviour change and activities of
      daily living were completed. RESULTS: Depression was a cardinal feature in FTD
      caregivers, and it accounted for more than 58% of stress scores. Both depression
      and stress were significantly higher than in AD. Neither the severity of
      behaviour changes nor functional disability explained caregiver stress.
      CONCLUSION: Caregiver stress is a multidimensional construct, and FTD caregivers
      should receive more support than currently available. Depression plays a key role
      in coping ability.

PMID- 19155624
TI  - Emphysematous cholecystitis with pneumobilia.

PMID- 19155623
TI  - Plasma homocysteine levels and different forms of vascular disease in patients
      with dementia and other psychogeriatric diseases.
AB  - BACKGROUND: Total plasma homocysteine (tHcy) concentration is elevated in
      patients with psychogeriatric disease. There are many different determinants of
      plasma tHcy concentration, including the presence of vascular disease. METHOD: We
      investigated plasma tHcy levels in several different subgroups of vascular
      disease and also the relation between plasma tHcy and renal function in patients
      with psychogeriatric disease. RESULTS: All different groups of patients with
      vascular disease exhibited an elevated level of plasma tHcy compared to patients
      without vascular disease even after exclusion of patients with folate/cobalamin
      deficiency. Patients with elevated serum creatinine with or without vascular
      disease exhibited significantly increased plasma tHcy compared to the respective
      groups of patients without elevated serum creatinine. Patients with vascular
      dementia and Alzheimer's disease with concomitant vascular disease exhibited
      significantly increased plasma tHcy levels compared to patients without vascular
      disease. CONCLUSION: The presence of vascular disease increases the level of
      plasma tHcy and renal impairment further increases the elevated plasma tHcy
      level. Furthermore, the findings suggest similar influence on plasma tHcy
      turnover irrespective of whether the vascular disease is of cerebral or
      extracerebral origin or only manifests itself as arrhythmia or hypertension.

PMID- 19155625
TI  - Tooth crown foreign body appendicitis.

PMID- 19155626
TI  - Embolization as treatment of choice for bleeding peptic ulcers in high-risk
      patients.
AB  - BACKGROUND/AIM: Peptic ulcers are the most common cause of acute upper
      gastrointestinal bleedings in the digestive tract. Most patients are poor
      surgical candidates. The aim was to describe the efficacy of embolization as the
      treatment of choice for bleeding peptic ulcers in high-risk patients when
      endoscopic treatment failed. METHODS: All patients who underwent a selective
      embolization of branches of the superior mesenteric artery and/or branches of the
      gastroduodenal artery for a bleeding peptic ulcer in the period January 2004
      until December 2007 were included in this retrospective descriptive study. We
      examined the known risk factors for surgery and mortality in upper
      gastrointestinal bleeding due to peptic ulcers and describe the clinical course
      and outcome. Primary endpoints were the primary technical success and the
      clinical success rates. The secondary endpoint was the 30-day mortality. RESULTS:
      16 patients were included. All patients had at least two risk factors for surgery
      and mortality. The clinical success rate was 81% (13/16). The first embolization
      failed in 3 patients, 1 was successful re-embolized and 2 were operated upon
      without re-embolization. The primary technical success rate, i.e. bleedings
      controlled by radiologic intervention, was 88% (14/16). 6 patients died due to
      non-embolization-related problems; 5 of them developed upper gastrointestinal
      bleeding during a stay in the hospital. CONCLUSION: Embolization was a
      successful, minimal invasive alternative for surgical intervention in high-risk
      patients with upper gastrointestinal bleeding after failure of endoscopic
      treatment.

PMID- 19155627
TI  - Additional value of external ultrasonography of the neck after CT and PET
      scanning in the preoperative assessment of patients with esophageal cancer.
AB  - INTRODUCTION: Lymphatic dissemination of a (non-cervical) esophageal tumor to the
      neck is generally considered as distant metastasis. The aim of this study was to
      determine the additional value of external ultrasonography (US) to detect
      lymphatic metastasis to the neck after normal CT scan (CT) with or without normal
      PET scan (PET). METHODS: Between January 2003 and December 2005, 306 patients
      were analyzed for esophageal cancer in our department. A total of 233 patients
      underwent both CT and external US of the neck. PET was performed in 109 of these
      patients as part of a prospective cohort study. Fine needle aspiration (FNA) was
      only performed if external US reported suspected lymph nodes. FNA was defined as
      gold standard. RESULTS: In 176 patients (76%), CT did not identify any suspected
      nodes, but external US disagreed in 36 of them. In 9 of these patients, FNA
      confirmed metastasis, resulting in an additional value of external US after
      normal CT scanning of 5% (9/176). In 74 patients (68%), CT and PET did not
      identify any suspected nodes, but external US disagreed in 11 of them. In 3 of
      these patients, FNA confirmed metastasis, resulting in an additional value of
      external US after normal CT and PET of 4% (3/74). CONCLUSION: Considering its
      minimal invasiveness and wide availability in combination with the importance of
      the potential therapeutic consequences, we conclude that external US of the neck
      should be part of the routine diagnostic work-up in patients with esophageal
      cancer, even after normal CT and PET scanning.

PMID- 19155628
TI  - Surgical outcome and long-term follow-up after segmental colorectal resection in
      women with a complete obstruction of the rectosigmoid due to endometriosis.
AB  - INTRODUCTION: Intestinal involvement is reported in up to 12% of women with
      endometriosis. Complete large bowel obstruction is a rare complication of
      intestinal endometriosis. It is estimated to occur in less than 1% of the cases.
      OBJECTIVE: The aim of this study is to evaluate the surgical outcome and long
      term follow-up after segmental colorectal resection in women with a complete
      obstruction of the rectosigmoid due to endometriosis. In addition, the diagnostic
      work-up is described and discussed in view of the current literature. PATIENTS
      AND METHODS: We present a case series of 5 patients with a complete obstruction
      of the rectosigmoid due to endometriosis who were finally treated in our hospital
      within a multidisciplinary endometriosis team. We retrospectively analyzed all
      patients with this condition who were referred in the period January 2000 to
      December 2006. RESULTS: All patients (mean age 31.8 years, range 25-43 years)
      underwent emergency surgery resulting in a diverting colostomy before referral to
      our hospital. The principal diagnostic tool used was magnetic resonance imaging
      which demonstrated in all patients multiorgan endometriosis with complete
      obstruction of the rectosigmoid. Thereafter, all patients underwent a segmental
      colorectal resection by re-laparotomy. The diagnosis intestinal endometriosis was
      histologically confirmed in all cases. After surgery no major complications
      occurred. During a follow-up of 18-36 months, residual symptoms such as chronic
      constipation, deep dyspareunia and chronic pelvic pain were reported in 2
      patients. No recurrences of intestinal endometriosis occurred. CONCLUSION: In our
      case series, segmental colorectal resection showed a favorable surgical outcome
      with no major complications. In the long-term follow-up, a limited number of
      residual symptoms were reported and no recurrences occurred. Intestinal
      endometriosis as a cause of bowel obstruction is often a diagnostic challenge
      mimicking a broad spectrum of diseases. It should be included in the differential
      diagnosis in women of reproductive age presenting with any symptoms of bowel
      obstruction. Magnetic resonance imaging is recommended as the primary imaging
      technique in such cases. In our opinion, these patients should be treated in a
      multidisciplinary setting.

PMID- 19155629
TI  - Measurements of subcutaneous tissue PO2 reflect oxygen metabolism of the small
      intestinal mucosa during hemorrhage and resuscitation. An experimental study in
      pigs.
AB  - BACKGROUND: The first tissues to be deprived of perfusion and oxygenation in a
      hypovolemic situation and the last ones to be reperfused are the subcutaneous
      tissue and the gastrointestinal mucosa. We hypothesized that measurements of
      subcutaneous tissue gases and pH might reflect simultaneous changes in
      oxygenation of the intestinal mucosa. The aim of this study was to evaluate
      tissue gases and pH as measures of tissue oxygenation and tissue oxygen
      metabolism in subcutaneous and intestinal tissues simultaneously. MATERIAL AND
      METHODS: Five out of 17 domestic pigs (weight 21-25 kg) were used as controls
      without bleeding. Twelve animals were bled in 3 steps, 10% of their calculated
      blood volume at each step. The removed blood, crystalloid and colloid were
      thereafter infused, and animals were stabilized for 30 min. Measurements were
      made after each step of bleeding, retransfusion and stabilization. Before
      bleeding, all animals had a sensor (Paratrend 7) implanted subcutaneously in the
      left groin for measurements of tissue gases and pH (P(sc)O(2), P(sc)CO(2) and
      pH(sc)). Catheters were positioned in the jugular vein, portal vein, carotid
      artery, pulmonary artery and femoral artery for infusion, bleeding and oxygen
      monitoring. Via a midline laparotomy, 2 silicon tonometers (TRIP sigmoid
      catheters) were positioned in the ileum and sigmoid colon for measurements of
      PCO(2) and pH (P(iI)CO(2), P(si)CO(2), pH(iI) and pH(si)). Blood flow in the
      portal vein was measured by an ultrasound probe (H6SB) and a Clark electrode
      (Cardiff tissue oxymeter) was used for serosal PO(2) measurements of the ileum
      (P(iI)O(2)) and sigmoid colon (P(si)O(2)). RESULTS: After the first step of
      bleeding, P(sc)O(2) decreased from 64 +/- 17 to 56 +/- 22 mm Hg (SD; p < 0.05).
      P(sc)CO(2) and pH(sc) did not change. P(iI)CO(2) increased from 64 +/- 14 to 79
      +/- 14 mm Hg (p < 0.05), P(si)CO(2) increased from 77 +/- 16 to 90 +/- 18 mm Hg
      (p < 0.05). pH(iI) decreased from 7.15 +/- 0.09 to 7.03 +/- 0.09 (p < 0.05).
      P(iI)O(2) and P(si)O(2) decreased, but not significantly until steps of further
      bleeding. After re-transfusion and stabilization, P(sc)O(2) and P(iI)CO(2)
      returned to baseline. CONCLUSION: Measurements of subcutaneous PO(2) are
      sensitive to bleeding and resuscitation and reflect oxygen metabolism in the
      small intestinal mucosa as measured by PCO(2) and pH.

PMID- 19155630
TI  - Regeneration of autotransplanted avascular lymph nodes in the rat is improved by
      platelet-rich plasma.
AB  - The aim of this study was to verify that subcutaneous lymph node transplantation
      inducing lymphatic regeneration is possible in healthy adult rats, in analogy to
      results obtained in other species. This rat model was used to determine the
      effects of lymph node fragmentation as well as sheep erythrocytes and platelet
      rich plasma injection on the regeneration of the transplanted lymph nodes. The
      results show for the first time that the rat is an adequate model to study the
      regeneration of transplanted lymph nodes. Lymph node fragmentation seems to
      affect transplant regeneration negatively. An immune challenge by injection of
      sheep erythrocytes in the drainage area of the transplanted lymph nodes does not
      improve fragment regeneration. However, injection of syngeneic platelet-rich
      plasma containing several growth factors resulted in an improvement in
      regeneration. Lymph node fragment regeneration, although still experimental,
      could be relevant for lymphedema prevention. Acquired lymphedema has a high
      prevalence in developed countries as a consequence of the removal and/or
      radiotherapy of tumor-draining lymph nodes in cancer patients. This disease
      causes lifelong disability due to chronic swelling and increased risk of
      infections. It currently lacks an effective treatment.

PMID- 19155631
TI  - Thromboxane A(2) contributes to the mediation of flow-induced responses of
      skeletal muscle venules: role of cyclooxygenases 1 and 2.
AB  - BACKGROUND: It has been shown that increases in intraluminal flow elicit dilation
      in venules, but the mediation of response is not yet clarified. We hypothesized
      that - in addition to nitric oxide (NO) and dilator prostaglandins (PGI(2)/
      PGE(2)) - thromboxane A(2) (TxA(2)) contributes to the mediation of flow-induced
      responses of venules. METHODS AND RESULTS: Isolated rat gracilis muscle venules
      (259 +/- 11 microm at 10 mm Hg) dilated as a function of intraluminal flow, which
      was augmented in the presence of the TxA(2) receptor antagonist SQ 29,548 or the
      TxA(2) synthase inhibitor ozagrel. In the presence of SQ 29,548, indomethacin or
      Nomega-nitro-L-arginine methyl-ester decreased flow-induced dilations, whereas in
      their simultaneous presence dilations were abolished. The selective
      cyclooxygenase (COX) 1 inhibitor SC 560 reduced, whereas the selective COX-2
      inhibitor NS 398 enhanced flow-induced dilations. Immunohistochemistry showed
      that both COX-1 and COX-2 are present in the wall of venules. CONCLUSION: In
      skeletal muscle venules, increases in intraluminal flow elicit production of
      constrictor TxA(2), in addition to the dilator NO and PGI(2)/PGE(2), with an
      overall effect of limited dilation. These mediators are likely to have important
      roles in the multiple feedback regulation of wall shear stress in venules during
      changes in blood flow velocity and/or viscosity.

PMID- 19155632
TI  - eNOS activation induced by a polyphenol-rich grape skin extract in porcine
      coronary arteries.
AB  - BACKGROUND/AIMS: Drinking red wine is associated with a decreased mortality from
      coronary heart diseases. This study examined whether polyphenols contained in a
      grape skin extract (GSE) triggered the endothelial formation of nitric oxide (NO)
      and investigated the underlying mechanism. METHODS: Vascular reactivity was
      assessed in organ chambers using porcine coronary artery rings in the presence of
      indomethacin (a cyclooxygenase inhibitor) and charybdotoxin plus apamin
      (inhibitors of endothelium-derived hyperpolarizing factor-mediated responses).
      The phosphorylation level of Src, Akt and endothelial NO synthase (eNOS) were
      assessed by Western blot analysis, and the formation of reactive oxygen species
      (ROS) was investigated using dihydroethidine and dichlorodihydrofluorescein.
      RESULTS: GSE-induced endothelium-dependent relaxations were abolished by N(G)
      nitro-L-arginine (an eNOS inhibitor) and ODQ (a soluble guanylyl cyclase
      inhibitor), and they were reduced by MnTMPyP, polyethyleneglycol catalase, PP2
      (an inhibitor of Src kinase) and wortmannin (an inhibitor of phosphoinositide 3
      kinase). GSE caused phosphorylation of Src, which was prevented by MnTMPyP. It
      also caused phosphorylation of Akt and eNOS, which were prevented by MnTMPyP,
      polyethyleneglycol catalase, PP2, wortmannin and LY294002. GSE elicited the
      formation of ROS in native and cultured endothelial cells, which was prevented by
      MnTMPyP. CONCLUSIONS: GSE causes endothelium-dependent NO-mediated relaxations of
      coronary arteries. This effect involves the intracellular formation of ROS in
      endothelial cells leading to the Src kinase/phosphoinositide 3-kinase/Akt
      dependent phosphorylation of eNOS.

PMID- 19155633
TI  - Left ventricular hypertrophy induced by reduced aortic compliance.
AB  - AIM: It was the aim of this study to investigate the long- term effects of
      reduced aortic compliance on cardiovascular hemodynamics and cardiac remodeling.
      METHOD: Sixteen swine, divided into 2 groups, a control and a banding group, were
      instrumented for pressure and flow measurement in the ascending aorta. Teflon
      prosthesis was wrapped around the aortic arch in order to limit wall compliance
      in the banding group. Hemodynamic parameters were recorded throughout a 60-day
      period. After sacrifice, the mean cell surface of the left ventricle was
      documented. RESULTS: Banding decreased aortic compliance by 49 +/- 9, 44 +/- 16
      and 42 +/- 7% on the 2nd, 30th and 60th postoperative day, respectively (p <
      0.05), while systolic pressure increased by 41 +/- 11, 30 +/- 11 and 35 +/- 12%
      (p < 0.05), and pulse pressure by 86 +/- 27, 76 +/- 21 and 88 +/- 23%,
      respectively (p < 0.01). Aortic characteristic impedance increased significantly
      in the banding group. Diastolic pressure, cardiac output and peripheral
      resistance remained unaltered. The mean left ventricular cell surface area
      increased significantly in the banding group. CONCLUSIONS: Acute reduction in
      aortic compliance results in a significant increase in characteristic and input
      impedance, a significant decrease in systemic arterial compliance and a
      subsequent increase in systolic and pulse pressures leading to left ventricular
      hypertrophy.

PMID- 19155634
TI  - Lymphedema development and lymphatic function following lymph node excision in
      sheep.
AB  - BACKGROUND: Our objective was to develop an animal model of postsurgical
      lymphedema that would permit quantitation of edema and lymphatic function after
      the removal of a single popliteal lymph node in sheep. METHODS: As a measure of
      lymph transport, (125)I-human serum albumin was injected into prenodal vessels at
      8, 12 and 16 weeks after nodal excision, and plasma levels of the protein tracer
      were used to calculate the transport rate of the tracer to blood (percent
      injected per hour). Edema was quantified from the circumferential measurement of
      the hind limbs. RESULTS AND CONCLUSIONS: Following nodal excision, the limbs
      became progressively more edematous up to 3 days after nodectomy. After this, the
      swelling decreased but had not resolved even at 16 weeks after surgery. Compared
      with control limbs (17.2 +/- 0.6; n = 7), lymphatic function was depressed at 8
      weeks after surgery (10.6 +/- 1.5; n = 7). At 12 (14.4 +/- 1.0; n = 7) and 16
      weeks (13.9 +/- 1.0; n = 6), regeneration of lymphatic vessels at the excision
      site helped to restore about 80% of lymphatic capacity. These techniques may be
      helpful in understanding the pathophysiology associated with cancer-related
      postsurgical lymphedema and may facilitate the development of new strategies to
      treat or prevent this condition.

PMID- 19155636
TI  - Correction towards normal hemoglobin values in chronic kidney disease: what is
      the current evidence regarding mortality and morbidity outcomes?
AB  - BACKGROUND: Recent studies, in which the cardiovascular risk and mortality
      associated with high and low hemoglobin target values, respectively, have been
      investigated, challenged the concept that hemoglobin normalization improves
      prognosis. METHODS: The results of these studies are reviewed with respect to
      differences in study populations, study design and methodological limitations to
      provide guidance for their interpretation and relevance for clinical practice.
      RESULTS: There are important differences with respect to enrolled populations,
      design and conduct of the studies. Each study has its specific, inherent
      methodological limitations. Importantly, there is no statistically significant
      and consistent pattern of negative results for cardiovascular and mortality
      outcomes, although in general outcomes are not in favor of hemoglobin
      normalization. On the other hand, the reported data on quality of life are
      consistently and significantly better with higher hemoglobin values. CONCLUSIONS:
      Recent evidence from large outcome studies suggested an increased risk associated
      with hemoglobin normalization. On the other side, several study-inherent and
      methodological limitations must be considered before simply extrapolating the
      negative findings of these studies into clinical practice. However, until new
      evidence becomes available from ongoing and future clinical studies, an upper Hb
      limit of 12 g/dl should not be exceeded.

PMID- 19155635
TI  - Development of a novel transgenic rat overexpressing the P2Y(2) nucleotide
      receptor using a lentiviral vector.
AB  - The G protein-coupled P2Y(2) nucleotide receptor (P2Y(2)R) is upregulated in
      response to stress and tissue injury and has been postulated to play a role in
      chronic inflammation seen in atherosclerosis, Alzheimer's disease and Sjogren's
      syndrome. The role of P2Y(2)R upregulation in vivo is poorly understood, in part
      due to the lack of a P2Y(2)R overexpressing animal model. The P2Y(2)R
      overexpressing transgenic rat was generated using a lentiviral vector. Rats
      overexpressing P2Y(2)R showed a significant increase in P2Y(2)R mRNA levels in
      all tissues screened as compared to nontransgenic rats. Fura 2 imaging of smooth
      muscle cells (SMCs) isolated from aorta indicated that the percentage of cells
      exhibiting increases in the intracellular free calcium concentration in response
      to P2Y(2)R agonists was significantly greater in freshly isolated SMCs from
      transgenic rats than wild-type controls. Histopathological examination of tissues
      revealed that P2Y(2)R overexpressing rats develop lymphocytic infiltration in
      lacrimal glands and kidneys as early as at 3 months of age. These rats show
      similarities to patients with Sjogren's syndrome who display lymphocyte-mediated
      tissue damage. This transgenic rat model of P2Y(2)R overexpression may prove
      useful for linking P2Y(2)R upregulation with chronic inflammatory diseases,
      neurodegenerative diseases and Sjogren's syndrome.

PMID- 19155637
TI  - The potential of phage therapy in bacterial infections of the eye.
AB  - Antibiotic resistance has become a major health challenge which poses a
      significant threat, also in ophthalmology. For example, methicillin-resistant
      Staphylococcus aureus may cause dramatic complications, including bilateral
      blindness as a consequence of orbital cellulitis and panophthalmitis. This menace
      has provoked a greatly revived interest in phage therapy. In recent years, a
      number of papers have been published suggesting its efficacy in animal and human
      bacterial infections, but none of them addressed the phage potential in
      ophthalmology, which is the subject of this mini review.

PMID- 19155638
TI  - Mean platelet volume in patients with slow coronary flow and its relationship
      with clinical presentation.
AB  - OBJECTIVES: We investigated mean platelet volume (MPV) in patients with slow
      coronary flow (SCF) and its possible relationship with clinical presentation.
      STUDY DESIGN: The study included 50 patients with SCF and otherwise normal
      coronary arteries and 22 patients (control group) with normal coronary arteries.
      In the SCF group, there were 26 patients with stable angina pectoris (SAP), and
      24 patients with unstable angina pectoris (USAP). Coronary blood flow was
      measured using the TIMI frame count. To determine MPV, blood samples with K3 EDTA
      were processed after one hour of venipuncture. The relationship between MPV and
      SCF was sought. RESULTS: The mean TIMI frame count was markedly increased in
      patients with SCF compared to controls (p<0.0001). No significant differences
      existed between the groups with regard to white blood cell and platelet counts.
      Patients with SCF had significantly higher MPV values compared to controls (9.4+/
      2.3 fl vs 8.1+/-2.0 fl, p=0.014). In subgroup analysis, MPV was significantly
      increased only in patients presenting with USAP, compared to patients with SAP
      (p=0.044) and controls (p=0.002). There was a positive correlation between the
      mean TIMI frame count and MPV in patients with SCF (r=0.32, p=0.01). In
      multivariate analysis, MPV was the only independent predictor of SCF (p=0.006,
      odds ratio=1.305, 95% CI=0.985-1.730). CONCLUSION: Our findings show that MPV is
      increased in patients with SCF, and SCF patients presenting with USAP exhibit
      significantly increased MPV values, suggesting an altered platelet reactivity and
      aggregation which may require effective anti-platelet therapy in this patient
      subgroup.

PMID- 19155639
TI  - [High levels of high-sensitivity C-reactive protein and impaired autonomic
      activity in smokers].
AB  - OBJECTIVES: We investigated the relationship between high sensitivity C-reactive
      protein (hs-CRP) activity and autonomic nervous activity using heart rate
      variability in smokers. STUDY DESIGN: The study consisted of 136 healthy
      subjects, including 66 smokers (35 women, 31 men; mean age 36 years) and 70
      nonsmokers (43 women, 27 men; mean age 34 years). Serum samples were collected
      from all the subjects. Three-channel, 24-hr Holter monitoring was performed to
      derive the mean heart rate, standard deviation of normal NN intervals (SDNN),
      standard deviation of 5-minute mean NN intervals (SDANN), root mean square
      differences of successive NN intervals (RMSSD), high- (HF) and low- (LF)
      frequency power components, and the LF/HF ratio. RESULTS: In smokers, the mean
      duration of smoking was 13.6+/-8.2 years (range 3 to 45 years), and the mean
      number of cigarettes consumed per day was 16.3+/-7.1 (range 5 to 40). Smokers
      exhibited significantly higher mean heart rate, hs-CRP and fibrinogen levels,
      mean platelet volume, white blood cell count, LF, and LF/HF ratio, with
      significantly lower SDNN, SDANN, RMSSD, and HF values. In smokers, hs-CRP was
      correlated with the number of cigarettes consumed per day, duration of smoking,
      fibrinogen level, mean platelet volume, white blood cell count, LF, and LF/HF
      ratio, and inversely correlated with HF, SDNN, and SDANN. Even smoking a single
      cigarette resulted in an acute, 0.07-fold increase in the hs-CRP level
      (p<0.0001). In linear regression analysis, both the number of cigarettes consumed
      per day (beta=0.52, p=0.011) and duration of smoking (beta=0.073, p<0.0001) had
      an independent effect on the hs-CRP level. CONCLUSION: Smoking both impairs the
      sympathovagal balance and increases the hs-CRP activity in otherwise healthy
      smokers, the combination of which would probably contribute to a higher rate of
      cardiovascular events.

PMID- 19155640
TI  - The relationship between nonalcoholic fatty liver disease and the severity of
      coronary artery disease in patients with metabolic syndrome.
AB  - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is an important complication
      of metabolic syndrome (MS). We investigated the possible relationship between
      NAFLD and angiographical severity of coronary artery disease (CAD) in patients
      with MS. STUDY DESIGN: This prospective study included 80 patients (35 men, 45
      women; mean age 63+/-10 years; range 42 to 80 years) with a diagnosis of MS
      according to the ATP III criteria. All patients underwent abdominal
      ultrasonography to detect NAFLD. Coronary angiography was performed for stable
      angina pectoris (n=48), unstable angina pectoris (n=21), and prognostic reasons
      (n=11). The severity of CAD was assessed by the number of vessels involved
      (vessel score) and the severity score (Gensini score). Significant stenosis was
      defined as 70% or greater reduction in lumenal diameter. RESULTS: Ultrasonography
      revealed NAFLD in 43 patients (53.8%). Patients with NAFLD had significantly
      higher body mass index, waist circumference, and serum triglyceride level, and
      significantly lower HDL-cholesterol level (p<0.001). Coronary angiography showed
      significantly higher vessel (2.5+/-0.9 vs 1.0+/-1.0) and CAD severity scores
      (90.2+/-40.0 vs 36.4+/-28.9) in patients with NAFLD (p<0.001). Univariate
      analysis showed that the presence of NAFLD (r=0.61, p<0.001), grade of NAFLD
      (r=0.42, p<0.001), and patient age (r=0.36, p=0.002) were significantly
      correlated with the CAD severity score. In multivariate linear regression
      analysis, the presence of NAFLD was the only independent factor affecting the CAD
      severity score (beta: 1.35, p<0.001). CONCLUSION: The presence of NAFLD is
      associated with more severe CAD, requiring that patients with MS be investigated
      for the presence of NAFLD and those with NAFLD be attentively followed-up for the
      presence and severity of CAD.

PMID- 19155641
TI  - Prognostic value of troponin T and homocysteine in patients with end-stage renal
      disease.
AB  - OBJECTIVES: The most important cause of increased mortality in end-stage renal
      disease (ESRD) is cardiovascular diseases. We investigated the prognostic value
      of cardiac troponin T (cTnT) and homocysteine in the long-term follow-up of ESRD
      patients. STUDY DESIGN: The study included 78 patients (54 males, 24 females;
      mean age 53.2+/-16.6 years) with ESRD, who had been on hemodialysis treatment for
      at least three months. Baseline troponin T and homocysteine levels were measured
      and the patients were followed-up from March 2002 to May 2007 for major adverse
      cardiovascular events (MACE). RESULTS: Major adverse cardiovascular events
      occurred in 26 patients (33.3%), including cerebrovascular events (n=3, 3.9%),
      congestive heart failure (CHF) (n=18, 23.1%), coronary artery disease (CAD)
      (n=19, 24.4%), and death (n=19, 24.4%). Two-thirds of diabetic patients developed
      MACE and the mean age in the MACE group was significantly greater (p<0.001).
      Troponin T levels were significantly higher in patients who developed MACE
      (0.21+/-0.43 ng/ml vs 0.06+/-0.28 ng/ml, p=0.002), whereas homocysteine levels
      did not differ significantly between the two groups (p=0.82). For a cutoff value
      of 0.10 ng/ml, cTnT was > or =0.1 ng/ml in 17 patients (21.8%), and <0.10 ng/ml
      in 61 patients (78.8%). Patients having a cTnT level of > or =0.10 ng/ml showed
      significantly higher rates of MACE (64.7% vs 24.6%; p=0.003), CHF (47.1% vs
      16.4%; p=0.02), and death (52.9% vs 16.4%; p=0.004). There was also a greater
      tendency to CAD in this group (41.2% vs 19.7%, p=0.10). In multivariate logistic
      regression analysis, age and diabetes mellitus were the independent predictors of
      MACE development. CONCLUSION: Homocysteine levels cannot predict MACE in ESRD
      patients in the long-term follow-up. Despite a significantly higher incidence of
      MACE in patients with high cTnT levels, cTnT was not an independent predictor of
      cardiovascular outcome.

PMID- 19155643
TI  - [Assessment of mitral stenosis with isovolumic myocardial acceleration].

PMID- 19155642
TI  - Evaluation of the severity of mitral stenosis with a new index: isovolumic
      myocardial acceleration.
AB  - OBJECTIVES: Although right ventricular (RV) systolic dysfunction is an important
      indicator for the severity of mitral stenosis (MS), its diagnosis is difficult
      before systemic signs of venous congestion occur. We assessed the association
      between tissue Doppler (TDI)-derived isovolumic myocardial acceleration (IVA) and
      the severity of MS. STUDY DESIGN: The study included 112 MS patients (79 mild to
      moderate, 33 severe MS). Two-dimensional and Doppler echocardiographic parameters
      (mitral valve area, transmitral diastolic gradients, pulmonary artery pressure,
      RV fractional shortening, pulmonary flow acceleration time, tricuspid valve
      annular systolic excursion) were calculated. Additionally, TDI-derived systolic
      velocities of the tricuspid annulus (IVA, peak myocardial velocity during
      isovolumic contraction-IVV, peak systolic velocity during ejection period-Sa)
      were recorded. The results were compared with those of 60 age- and sex-matched
      healthy controls. RESULTS: All TDI-derived systolic velocities (IVV, Sa and IVA)
      were significantly decreased in patients with MS (p<0.0001). However, IVA was the
      only parameter to distinguish the severity of MS (p<0.0001). It also showed
      significant correlations with the following parameters with which IVV and Sa were
      not correlated: mitral valve area (r=0.79, p<0.0001), mean (r=-0.54, p<0.0001)
      and maximum (r=-0.58, p<0.0001) transmitral diastolic gradients, pulmonary artery
      pressure (r=-0.54, p<0.0001), and left atrial diameter (r=-0.68, p<0.0001). The
      ROC curve analysis showed that an IVA of <2.9 m/sec2 predicted MS patients with
      86% sensitivity, 87% specificity, and an IVA of <2 m/sec2 predicted severe MS
      with 82% sensitivity and 77% specificity. CONCLUSION: Tissue Doppler-derived
      right ventricular IVA may be used as an adjunctive, alternative noninvasive
      parameter to determine the severity of MS in patients without signs of systemic
      venous congestion.

PMID- 19155644
TI  - Calcific constrictive pericarditis in a patient presenting with right heart
      failure.
AB  - A 45-year-old man presented with gradual dyspnea, abdominal distension, and pedal
      edema of six-month history. A lateral chest x-ray demonstrated severe, dense
      calcification of the pericardium. Two-dimensional and pulsed-wave Doppler
      echocardiography demonstrated signs of constrictive pericarditis. Chest computed
      tomography showed diffuse, incomplete calcification of the pericardium and a
      dilated superior vena cava. The patient refused pericardiectomy, so medical
      treatment was instituted.

PMID- 19155645
TI  - [Acute anterior myocardial infarction due to left main coronary artery
      thrombosis].
AB  - Acute anterior myocardial infarction (MI) due to left main coronary artery
      thrombosis is a rare entity with a very high mortality rate. A 72-year-old male
      patient was admitted with chest pain of two-hour onset that appeared during
      syncope. Electrocardiography showed first-degree AV block, right bundle branch
      block, left anterior fascicular block, ST-segment elevation of 5 mm in lead aVR,
      and significant ST depression in anterior derivations, suggesting acute anterior
      MI. Coronary angiography showed total occlusion of the left main coronary artery.
      During consultation for emergency operation, he developed hypotension. An intra
      aortic balloon pump was inserted and inotropic support was initiated. He required
      several attempts of cardioversion due to persistent attacks of ventricular
      tachycardia. He developed respiratory arrest, requiring endotracheal intubation
      mechanical ventilation. The patient died due to recurrent attacks of ventricular
      fibrillation and subsequent development of asystole during primary percutaneous
      coronary intervention.

PMID- 19155646
TI  - [Combined anterior and inferior ST-segment elevation during exercise test: a case
      report].
AB  - Exercise-induced ST-segment elevation without Q waves is a rare situation. Its
      frequent causes are slow coronary flow leading to serious myocardial ischemia,
      significant coronary stenosis, and coronary vasospasm. Effort-related combined
      anterior and inferior ST elevation is even rarer. A 49-year-old man was admitted
      with exercise-induced chest pain. During exercise stress test, he developed
      typical retrosternal chest pain with combined anterior and inferior ST elevation
      on electrocardiography. Coronary angiography showed an anomalous left circumflex
      coronary artery arising from the right sinus of Valsalva. A plaque and diffuse
      spasm were noted in the middle portion of the left anterior descending coronary
      artery. Intracoronary nitroglycerin administration resulted in complete
      resolution of the spasm. The patient was discharged on medical therapy.

PMID- 19155647
TI  - [Successful percutaneous cryoablation of recurrent atrioventricular nodal re
      entrant tachycardia after radiofrequency ablation].
AB  - A 21-year-old male patient underwent radiofrequency catheter ablation for
      refractory attacks of supraventricular tachycardia. One month after the
      procedure, he developed recurrent atrioventricular nodal re-entrant tachycardia,
      for which percutaneous cryoablation was performed. Programmed atrial stimulation
      at the end of cryoablation did not induce an atrio-His (AH) jump or tachycardia.
      During a four-month follow-up without any medications, the patient was free of
      any signs of tachycardia.

PMID- 19155648
TI  - Right atrial compression due to idiopathic right diaphragm paralysis detected
      incidentally by transthoracic echocardiography.
AB  - Unilateral diaphragm paralysis (UDP) is an important and often unrecognized cause
      of dyspnea. We report a 72-year-old man in whom UDP was incidentally detected by
      transthoracic echocardiography. He was asymptomatic at rest, but experienced
      dyspnea on exertion. Chest radiography was not pathognomonic in this case because
      the heart silhouette obscured the left diaphragmatic contour. Transthoracic
      echocardiography showed an extrinsic compression to the right atrium. Right
      atrial collapse was obvious during heart movements with variation upon
      respiratory movements. There was no pericardial effusion nor any solid mass
      lesion. Fluoroscopic sniff test demonstrated a significant paradoxical elevation
      of the paralyzed right diaphragm in inspiration. Thoracic and abdominal computed
      tomography scans did not show any other pathology. The diagnosis was made as
      idiopathic UDP.

PMID- 19155649
TI  - [Coexistence of partial anomalous pulmonary venous drainage and pulmonary atresia
      with ventricular septal defect: a report of two cases].
AB  - Coexistence of partial anomalous pulmonary venous drainage (PVD) and pulmonary
      atresia with ventricular septal defect (PA-VSD) is very rare with the exception
      of heterotaxy syndromes. We presented two cases of PA-VSD in which partial
      anomalous PVD was detected during pulmonary artery angiography. One was a six
      month-old girl who underwent cardiac catheterization to evaluate the chance of
      unifocalization. There were true pulmonary arteries and three major
      aortopulmonary collaterals. It was noted that the right upper pulmonary vein was
      in direct continuity with the right atrium. The second case was a 12-year-old
      girl who was previously diagnosed as having PA-VSD and absence of true pulmonary
      arteries, for which she had undergone two subsequent aortopulmonary shunt
      operations four years before. During cardiac catheterization, confluent but
      hypoplastic true pulmonary arteries and multiple minor aortopulmonary collaterals
      were detected. The right and left upper pulmonary veins were draining to the
      right atrium. It should be known that, albeit very rare, partial anomalous PVD
      may be present in PA-VSD cases, requiring careful evaluation of pulmonary venous
      drainage during echocardiographic and angiographic studies.

PMID- 19155650
TI  - [Treatment alternatives in mechanical valve thrombosis].
AB  - Mechanical valve thrombosis is a life-threatening complication, occurring in 0.5%
      to 8% of left-sided mechanical prosthetic valves, and in 20% of tricuspid valve
      prostheses. Although surgery is the first-line treatment modality particularly in
      symptomatic obstructive mechanical valve thrombosis, it is associated with high
      rates of morbidity and mortality. Fibrinolytic therapy and thrombolytic therapy
      have also been used as an alternative to surgical treatment. The risk for
      cerebral thromboembolism associated with thrombolytic therapy seems to be the
      main limitation for its use in left-sided mechanical valve thrombosis. In this
      article, we reviewed the treatment alternatives in obstructive mechanical valve
      thrombosis in the light of relevant studies, with a brief presentation of our
      experience.

PMID- 19155651
TI  - [Coexistence of obstructive mechanical mitral valve and left atrial thrombosis].

PMID- 19155652
TI  - Delineation of a coronary artery to pulmonary artery fistula by multidetector
      computed tomography angiography.

PMID- 19155653
TI  - Thrombosed aortic dissection in an asymptomtic elderly patient.

PMID- 19155654
TI  - [The effect of plasma asymmetric dimethylarginine (ADMA) level and L
      arginine/ADMA ratio on the development of coronary collaterals].

PMID- 19155655
TI  - Treatment of iatrogenic pneumothorax on pacemaker implantation.

PMID- 19155656
TI  - Prevalence of coronary artery disease in low to moderate-risk asymptomatic women:
      a multislice computed tomography study.
AB  - OBJECTIVES: Traditional risk factors may underestimate the burden of subclinical
      atherosclerosis in women. Recently, multislice computed tomography (MSCT) has
      become widely available in detecting early coronary artery disease (CAD). We
      sought the prevalence of CAD in low to moderate-risk asymptomatic women by MSCT
      coronary artery calcium (CAC) scoring and coronary angiography. STUDY DESIGN: The
      study included 185 women (mean age 57+/-12 years) without known CAD and diabetes,
      with low or moderate risk for CAD based on traditional risk scoring. Coronary
      artery calcium scoring and coronary angiography were performed by MSCT, which
      included a segment-based plaque detection and characterization of calcification.
      The plaques were classified based on the luminal stenotic effect (>50%). Patients
      with = or >1 stenotic plaque were classified as having obstructive CAD.
      Angiographic findings were compared with calcium scores. RESULTS: Coronary artery
      calcium scoring and coronary angiography detected CAD in 63 (34.1%) and 100
      (54.1%) women, respectively. In both groups, women were significantly older and
      had higher prevalences of hypertension and dyslipidemia. Coronary angiography
      showed CAD in 41 women (41%; 14.6% were obstructive) without CAC. These women
      were significantly younger than those with a positive CAC score (p<0.01). Age
      (p<0.02) and hypertension (p<0.05) were found as independent predictors of CAD
      detected by coronary angiography. CONCLUSION: Multislice computed tomography
      identified a subset of low-risk women who might be at higher risk than that
      suggested by current risk stratification strategies. Women, especially having
      hypertension and dyslipidemia may be potential candidates for further risk
      stratification by MSCT coronary angiography.

PMID- 19155657
TI  - [Does accompanying metabolic syndrome contribute to heart dimensions in
      hypertensive patients?].
AB  - OBJECTIVES: Metabolic syndrome (MetS) is associated with increased risk for
      cardiovascular events. We evaluated heart dimensions in hypertensive patients
      with MetS. STUDY DESIGN: The study included 75 hypertensive patients (34 males,
      41 females; mean age 51+/-9 years) without coronary artery disease. Patients were
      evaluated in two groups depending on the presence or absence of MetS. Age- and
      gender-matched 20 healthy subjects (9 males, 11 females; mean age 50+/-5 years)
      comprised the control group. The diagnosis of MetS was based on the presence of
      at least three of five MetS criteria. Hypertension was defined as arterial blood
      pressure exceeding 140/85 mmHg on three consecutive measurements or the use of
      antihypertensive drugs. Echocardiographic measurements included interventricular
      septal thickness, left ventricular internal diameter, posterior wall thickness,
      aortic diameter, left atrial diameter, relative wall thickness, and left
      ventricular mass. RESULTS: Metabolic syndrome was present in 32 hypertensive
      patients (42.7%; 18 males, 14 females). The mean number of MetS criteria was
      2.6+/-1.0 in the hypertensive group. Compared to the control group, patients with
      or without MetS exhibited significantly increased interventricular septum and
      posterior wall thickness, left atrial diameter, relative wall thickness, and left
      ventricular mass (p<0.05). The only significant difference between the two
      patient groups was that MetS was associated with a greater left atrial diameter
      (p=0.019). Left atrial diameter was correlated with the number of MetS criteria
      (r=0.51; p<0.001). CONCLUSION: Left ventricular dimensions are not influenced by
      MetS. Rather than MetS, hypertension is primarily responsible for changes in left
      ventricular dimensions. However, left atrial enlargement is more prominent in
      patients with MetS, suggesting that each MetS criterion contributes to left
      ventricular diastolic dysfunction.

PMID- 19155658
TI  - [The prevalence of angiographically significant coronary artery disease in
      patients with isolated secundum atrial septal defect].
AB  - OBJECTIVES: Atrial septal defect (ASD) and coronary artery disease (CAD) may
      coexist in adults, especially in the elderly. The aim of this study was to
      determine the prevalence of CAD in patients undergoing both catheterization for
      ASD and selective coronary angiography and to evaluate the relationship of CAD
      with symptoms and risk factors. STUDY DESIGN: The study included 138 consecutive
      patients (40 males, 98 females; mean age 54+/-10 years; range 31 to 74 years) who
      underwent catheterization for isolated secundum ASD and selective coronary
      angiography at the same session. The mean shunt was 2.6+/-0.8 in the patient
      group. Significant CAD was defined as the presence of = or >50% stenotic lesions
      during angiography. RESULTS: Significant CAD was detected in 12 patients (8.7%).
      Patients with CAD exhibited a higher mean age (61+/-10 vs 54+/-10 years, p=0.016)
      and male preponderance (83.3% vs 23.8%, p<0.001). Risk factors and hemodynamic
      parameters did not differ between the two groups. Laboratory parameters were also
      similar except for a higher triglyceride level in patients without CAD (123+/-64
      mg/dl vs 71+/-40 mg/dl, p=0.006). Angina pectoris was present in four patients
      (33.3%) in the CAD group, compared to 28 patients (22.2%) without CAD. For angina
      pectoris to predict CAD, the sensitivity, specificity, positive and negative
      predictive rates were 33.3%, 77.8%, 12.5%, and 92.5%, respectively. The
      corresponding figures were 50.0%, 33.3%, 6.7%, and 87.5% for at least one risk
      factor, and 16.7%, 82.5%, 8.3%, and 91.2% for combination of angina pectoris with
      at least one risk factor. CONCLUSION: Despite increased prevalence of CAD in
      adults, its prevalence is relatively low in patients with ASD. Thus, routine
      coronary angiography performed to detect CAD in patients with ASD increases
      complications and decreases cost-effectiveness.

PMID- 19155659
TI  - The predictive value of plasma brain natriuretic peptide for the recurrence of
      atrial fibrillation six months after external cardioversion.
AB  - OBJECTIVES: The aim of this study was to assess the predictive value of plasma
      brain natriuretic peptide (BNP) level for the recurrence of atrial fibrillation
      (AF) after successful cardioversion in patients with persistent AF. STUDY DESIGN:
      The study included 58 patients (36 females, 22 males; mean age 59 years) with
      preserved left ventricular function, who underwent successful electrical
      cardioversion for persistent AF. Plasma BNP levels were measured before, 30
      minutes and six months after cardioversion and electrocardiography was performed
      to assess AF recurrence. Echocardiography was performed in all the patients
      before cardioversion. RESULTS: At six months, 38 patients (65.5%) were in sinus
      rhythm (SR), whereas 20 patients (34.5%) reverted to AF. The mean baseline BNP
      level was significantly higher than that measured 30 minutes after cardioversion
      (255.6+/-159.6 pg/ml vs 70.5+/-57.0 pg/ml; p=0.00006). Patients who reverted to
      AF had significantly higher baseline (p=0.035) and six-month (p=0.001) BNP
      levels. In addition, they had a significantly greater decrease in BNP levels 30
      minutes after cardioversion than patients who remained in SR (-271.9+/-42.4 pg/ml
      vs -139.4+/-25.3 pg/ml; p=0.008). ROC analysis of this drop with the cutoff value
      of 200 pg/ml predicted AF recurrence at six months with 80% sensitivity and 86%
      specificity. There were no correlations between baseline BNP level and duration
      of AF. However, left atrium diameter showed a significant negative correlation
      with the baseline BNP level (for = or <40 mm, 41-45 mm, and = or >45 mm: 394.6
      pg/ml, 206.5 pg/ml, and 198.5 pg/ml, respectively; p=0.02). CONCLUSION: In
      patients with persistent AF, baseline plasma BNP level and the magnitude of its
      decrease after successful cardioversion may predict AF recurrence.

PMID- 19155660
TI  - [Combination of complete atrioventricular septal defect and tetralogy of Fallot:
      surgical management and its results].
AB  - OBJECTIVES: Complete atrioventricular septal defect (AVSD) with tetralogy of
      Fallot (TOF) is a rare congenital heart anomaly. We evaluated surgical results of
      total repair in patients with TOF and AVSD. STUDY DESIGN: Seven patients (5
      girls, 2 boys; age range 2.5 to 14 years) underwent total repair for AVSD and
      TOF. Three patients had Down syndrome. Three patients had previous systemic-to
      pulmonary shunt operations. Accompanying anomalies were left superior vena cava
      (n=2), left atrial isomerism (n=1), muscular VSD (n=1), and double outlet right
      ventricle (n=1). Preoperative diagnoses were based on echocardiographic
      examinations. The two-patch technique was used for surgical repair.
      Reconstruction of the right ventricular outflow tract was performed using
      transannular and infundibular patches in four and three patients, respectively.
      The follow-up period ranged from six months to nine years (mean 3.4+/-2.9 years).
      RESULTS: No mortality occurred throughout the follow-up period. Two patients had
      prolonged hospitalization (>1 month) due to pulmonary infection and sepsis. At
      the latest follow-up, functional capacity was NYHA class I in five patients, and
      class II in two patients. Final echocardiographic examinations showed mild left
      atrioventricular (AV) valve insufficiency in five patients, and mild (n=3) or
      moderate (n=1) right AV valve insufficiency. Two patients had mild residual
      pulmonary stenosis, and three patients with a transannular patch had free
      pulmonary insufficiency. All the patients had proper right and left ventricular
      functions and all were in sinus rhythm. CONCLUSION: With a proper surgical
      strategy and technique, AVSD and TOF can be corrected successfully. Long-term
      follow-up is necessary for AV valve dysfunction and pulmonary insufficiency.

PMID- 19155661
TI  - Antiphospholipid antibody syndrome leading to massive pulmonary embolism and
      sudden death.
AB  - Antiphospholipid antibody syndrome is associated with venous and arterial
      thromboembolism. Coexistence of pulmonary embolism and intracardiac thrombus is
      rarely encountered. A 33-year-old male patient presented with severe dyspnea
      three months after surgery for acute arterial embolism. On physical examination,
      blood pressure was 80/60 mmHg and breath sounds were weaker in the lower zone of
      the left lung. Severe lower limb edema was noted. On cardiac auscultation, the
      third heart sound was elicited. Electrocardiography showed only a sinusal
      tachycardia. Transthoracic echocardiography revealed a huge thrombus in the right
      atrium and another thrombus in the main pulmonary artery. Hematological analysis
      showed a high titration of antiphospholipid antibodies. A diagnosis of massive
      pulmonary embolism was considered. During preparation for emergency operation,
      the patient developed cardiovascular collapse, which did not respond to
      cardiopulmonary resuscitation.

PMID- 19155662
TI  - [Obstruction of the left ventricular outflow tract caused by bicuspid aortic
      valve and discrete subaortic membrane].
AB  - Bicuspid aortic valve is the most common congenital cardiac anomaly and it may
      often coexist with other congenital cardiac anomalies. Its coexistence with
      discrete subaortic membrane, causing obstruction of the left ventricular outflow
      tract is very rare. A 21-year-old male patient presented with complaints of
      exertional dyspnea and dizziness. On transthoracic echocardiography, the
      parasternal short-axis view showed a bicuspid aortic valve, and parasternal long
      axis color Doppler view showed a mosaic pattern in the subaortic region. A more
      careful examination of the parasternal long-axis views revealed a discrete
      subaortic membrane. Continuous-wave Doppler flow velocity obtained from the
      aortic valve was normal; however, a peak gradient of 30 mmHg was observed with
      the Valsalva maneuver. The fact that there are very few reports on this rare
      coexistence may be due to failure to recognize discrete subaortic membrane during
      echocardiographic examination.

PMID- 19155663
TI  - Single coronary artery anomaly: a report of three cases.
AB  - We presented three cases of anomalous single coronary artery detected
      incidentally during routine coronary angiography. The presenting symptoms were
      chest pain, angina pectoris, and exertional chest pain, respectively. In one case
      (male, 69 years), the single coronary artery gave off branches to the left
      anterior descending artery, left circumflex (LCx) artery, and right coronary
      artery (RCA) (type L-I). There were no atherosclerotic lesions. The patient's
      chest pain was thought to have a noncardiac origin and it did not recur during a
      12-month follow-up. In another case (male, 65 years), the single coronary artery
      originated from the right sinus of Valsalva, and gave off branches to the RCA and
      the left coronary system (type R-I). The patient underwent coronary artery bypass
      surgery for significant stenotic lesions in the LCx and RCA. He was free of
      angina pectoris within 12 months after surgery. In the third case (female, 48
      years), a single coronary ostium gave branches to the right and left coronary
      systems (type R-II-B). As the course of the coronary artery was between the aorta
      and pulmonary artery, surgery was recommended, but the patient refused surgery.

PMID- 19155665
TI  - Percutaneous extraction of a short, 0.038-inch guide wire retained in the right
      common iliac artery.
AB  - Percutaneous extraction of intravascular foreign bodies with the help of
      specifically designed devices is the standard method of treatment and should be
      attempted in appropriate cases before any surgical approach. The majority of
      retrieved materials are catheter fragments localized in the superior vena cava,
      right side of the heart, or pulmonary artery. During diagnostic coronary
      angiography of a 65-year-old man, a short, 0.038-inch guide wire was identified
      in the right common iliac artery. It was erroneously left there during arterial
      monitoring performed at another center. The guide wire was successfully removed
      percutaneously using a combination of "wire-balloon" technique without any
      available specifically designed device.

PMID- 19155664
TI  - A very rare cause of continuous murmur and coronary ischemia: high-flow coronary
      to-pulmonary artery fistula.
AB  - A 52-year-old woman presented with complaints of chest discomfort and angina
      radiating to the neck and left arm on exertion. She reported that the severity of
      angina was increasing after sublingual nitrate intake. Coronary angiography
      showed a high-flow fistula between the left main coronary artery and pulmonary
      artery. Left coronary arteries were normal, but there was a stenotic lesion in
      the right coronary artery. Coronary artery fistula was ligated successfully under
      bypass surgery. It was thought that the severity of myocardial ischemia caused by
      the high-flow fistula was aggravated by sublingual nitrate due to coronary steal
      phenomenon.

PMID- 19155666
TI  - A case of cardiac tamponade caused by tuberculous pericarditis.
AB  - A 71-year-old woman was admitted with a diagnosis of cardiac tamponade. Emergency
      transthoracic echocardiography showed a large amount of pericardial effusion
      compressing the whole heart. Pericardiocentesis was performed immediately and
      nearly 1 liter of hemorrhagic fluid was aspirated. Pathological result of the
      pericardiocentesis material was benign, acid-resistant bacteria were not found in
      the pericardial fluid, and bacteria cultures were negative. The only parameter
      suggesting tuberculous pericarditis was adenosine deaminase activity in the
      pericardial fluid, which was measured as 76 U/l. With antituberculosis therapy
      for six months, the patient showed complete improvement; no signs of
      deterioration were observed and echocardiographic findings were normal.

PMID- 19155667
TI  - [Safety of magnetic resonance imaging in patients with implanted cardiovascular
      devices].
AB  - Magnetic resonance imaging (MRI) is one of the most advanced diagnostic methods
      of radiologic imaging. In patients with implanted cardiovascular devices, there
      can be device malfunction and deterioration in the quality of diagnostic data as
      a result of MRI-related interferences. This article aimed to review MRI safety in
      patients with implanted cardiovascular devices.

PMID- 19155668
TI  - Spider in the heart.

PMID- 19155669
TI  - Large left ventricular pseudoaneurysm detected by 64-slice computed tomography.

PMID- 19155670
TI  - Pseudoaneurysm of the mitral-aortic intervalvular fibrosa after aortic valve
      replacement.

PMID- 19155671
TI  - [Disclosure of the diagnosis to the patient with head and neck cancer].
AB  - OBJECTIVES: The goal of this study was to elicit information on the feelings and
      thoughts of head and neck cancer patients at the time of disclosure of the
      diagnosis and to guide the physicians to a better communication with similar
      patients, taking into consideration general tendencies and the opinion of
      individual patients. PATIENTS AND METHODS: A questionnaire-based, retrospective
      study was performed between April 2005 and 2006, including 34 patients (26 males
      8 females; mean age 52 years; range 19 to 80 years) with head and neck cancer,
      who had undergone surgery as primary treatment, had been followed-up for at least
      two years, and were disease-free at the time of the study. A 30-item
      questionnaire was administered, consisting of multiple-choice and fill-in-the
      blank questions. RESULTS: The diagnosis of cancer was announced to most of the
      patients in the hospital by the physician. Most recalled the physicians' speech
      and how they felt, half of them describing depression and fear. The articulation
      of the informing physician was found very understandable and simple by almost all
      the patients. Although it was generally thought that the diagnosis had been
      announced in a comfortable place, taking their privacy into consideration and
      allocating enough time, 47% expressed their wish for a more friendly and
      affectionate communication. CONCLUSION: Evaluation of the effects of hearing a
      malignant diagnosis from the standpoint of a patient with head and neck cancer
      may make the physician's attitude more solicitous, affectionate, honest, and
      encouraging, which would further contribute to patient satisfaction and
      adaptation to treatment.

PMID- 19155672
TI  - [Effectiveness of rapid antigen test with throat gargle in detecting group A beta
      hemolytic streptococci].
AB  - OBJECTIVES: The most important disadvantage of rapid antigen tests (RAT) is low
      sensitivity for the diagnosis of group A beta-hemolytic streptococci (BHS). We
      determined the sensitivity, specificity, positive and negative predictive values
      of RAT in gargling samples. PATIENTS AND METHODS: The study included 106 patients
      (53 females, 53 males, mean age 22+/-12 years; range 16-65 years) with an initial
      diagnosis of tonsillopharyngitis. Swab samples were taken from the posterior
      pharyngeal wall and tonsil surface with a sterile cotton swab. Then, gargle
      samples were obtained by gargling for 10 seconds with sterile 0.9% NaCl to be
      examined by the RAT for group A BHS. Throat cultures were processed using
      standard microbiologic techniques. RESULTS: Throat cultures were positive in 12
      patients (11.3%) and negative in 94 patients (88.6%). Rapid antigen test yielded
      five positive (4.7%) and 101 negative (95.2%) results. The sensitivity and
      specificity rates of RAT with throat gargling were 41.7% and 100%, with positive
      and negative predictive values of 100% and 93.1%, respectively. CONCLUSION:
      Despite satisfactory specificity, positive and negative predictive rates of RAT
      with throat gargling, its low sensitivity limits its use for the diagnosis of
      group A BHS.

PMID- 19155673
TI  - [Evaluation of depth of invasion and tumor diameter in relation to tumor
      localization in laryngeal cancer].
AB  - OBJECTIVES: We investigated the relationship between tumor localization and depth
      of tumor invasion and tumor diameter. PATIENTS AND METHODS: Neck dissection
      specimens of 70 patients (mean age 61+/-10 years, range 38 to 77 years) who
      underwent laryngectomy for squamous cell carcinoma of the larynx were
      histopathologically re-examined with regard to the number and localization of
      metastatic lymph nodes, depth of tumor invasion, and tumor diameter. Three tumor
      groups (supraglottic, glottic, and transglottic) were compared with respect to
      depth of tumor invasion, tumor diameter, metastatic lymph nodes, and T-stage.
      RESULTS: The overall mean depth of tumor invasion was 7.06 mm, being 7.76 mm,
      7.05 mm, and 4.06 mm in supraglottic, transglottic, and glottic tumors,
      respectively. Compared to glottic tumors, depth of tumor invasion and tumor
      diameter were significantly higher in supraglottic and transglottic tumors
      (p<0.05). Depth of invasion showed a significant correlation with tumor diameter
      (p<0.05), whereas there was no correlation between depth of invasion and lymph
      node metastasis (p>0.05). In supraglottic tumors, depth of invasion significantly
      increased in parallel with T-stage (p<0.05). In transglottic and glottic tumors,
      however, there was no correlation between T-stage and depth of invasion (p>0.05).
      CONCLUSION: Our data show that depth of tumor invasion is related with tumor
      location and diameter in laryngeal cancers.

PMID- 19155674
TI  - [Thyroid masses: an analysis of 131 cases].
AB  - OBJECTIVES: We retrospectively analyzed patients undergoing surgery for thyroid
      masses. PATIENTS AND METHODS: A total of 131 patients (80 males, 51 females) who
      underwent surgery for thyroid masses between 1993 and 2007 were evaluated with
      respect to clinical findings, histopathologic diagnoses, and treatment
      modalities. RESULTS: The thyroid masses were found benign in 48.1% and malignant
      in 51.9% of the patients. Forty-one females (65%) and 22 males (35%) had benign
      thyroid masses, while 39 females (57%) and 29 males (43%) had malignant thyroid
      masses. According to histopathologic results, the most common benign and
      malignant diagnoses were multinodular goiter (n=57, 43.5%) and papillary
      carcinoma (n=50, 38.2%), respectively. The mean duration of complaints was 58
      months for benign and 30 months for malignant tumors. CONCLUSION: Thyroid
      operations are becoming increasingly common in otorhinolaryngologic surgical
      procedures.

PMID- 19155675
TI  - [Clinical signs and management strategies in thyroid masses].
AB  - OBJECTIVES: Patients who underwent surgery for thyroid masses were evaluated with
      regard to clinical symptoms, diagnostic and treatment methods, and the results of
      treatment. PATIENTS AND METHODS: The study included 92 patients (72 women, 20
      men; mean age 45 years; range 16 to 71 years). Clinical diagnoses were based on
      findings of ultrasonography, thyroid function tests, thyroid scintigraphy, and
      fine-needle aspiration biopsy. Operations performed were near-total thyroidectomy
      (n=40), hemithyroidectomy (n=25), bilateral subtotal thyroidectomy (n=16), and
      total thyroidectomy (n=11). Patients with carcinoma associated with neck lymph
      node metastasis also underwent lateral, anterolateral, modified radical, or
      radical neck dissections. RESULTS: Postoperative histopathologic diagnoses were
      benign colloid nodule (n=70), papillary carcinoma (n=16), medullary carcinoma
      (n=2), anaplastic carcinoma (n=2), and Basedow-Graves disease (n=2). Unilateral
      vocal cord paralysis developed in 11 patients (11.9%), five of which persisted
      beyond one year follow-up. Two patients (2.2%) had transient hypocalcemia and one
      patient (1.1%) had postoperative hematoma. CONCLUSION: Preoperative determination
      of the structure and confines of thyroid masses increases success rates of
      surgical procedures and minimizes complication rates.

PMID- 19155676
TI  - [Retropharyngeal abscesses: a retrospective analysis of 10 patients].
AB  - OBJECTIVES: Retropharyngeal abscess is a serious and life-threatening disease due
      to its anatomic location and potential to obstruct the upper airway. We evaluated
      the clinical characteristics, diagnosis, and treatment of patients with
      retropharyngeal abscesses. PATIENTS AND METHODS: The study included 10 patients
      (6 males, 4 females; mean age 9+/-11 years; range 4 months to 32 years) who
      received medical and surgical treatment with the diagnosis of retropharyngeal
      abscess. The patients were evaluated with respect to etiology, clinical symptoms
      and signs, treatment, complications, and hospital stay. RESULTS: The most
      frequent etiological factor was upper airway infection (70%), followed by dental
      abscess in two patients (20%), and soft tissue injury due to foreign body
      ingestion in one patient (10%). The presenting symptoms and signs included
      dysphagia (100%), respiratory distress (80%), limited neck motion (80%), fever
      (60%), and neck pain (50%). Treatment consisted of surgical drainage and
      parenteral antibiotic combination of cefazolin sodium and metronidazole. The mean
      hospital stay was 7.1+/-5.3 days. Complications were seen in two patients, being
      empyema and upper airway obstruction, respectively. CONCLUSION: Surgical drainage
      combined with early antibiotic treatment is an effective method in the management
      of retropharyngeal abscesses and in preventing complications.

PMID- 19155677
TI  - [The effectiveness of endoscopic sinus surgery in nasal polyposis].
AB  - OBJECTIVES: We evaluated the effectiveness and outcomes of functional endoscopic
      sinus surgery in the treatment of nasal polyposis. PATIENTS AND METHODS: The
      study included 407 patients (262 males, 145 females; mean age 42+/-12 years;
      range 20 to 76 years) with nasal polyposis. Of these, 102 patients (25%) had
      asthma, 25 patients (6.1%) had asthma and aspirin sensitivity, and 142 patients
      (34.8%) had anatomic variations. The patients were operated on using the
      Messerklinger and Wigand techniques. Functional endoscopic sinus surgery was
      performed bilaterally. Evaluations were made preoperatively and at six months by
      endoscopic examination and paranasal sinus computed tomography (Lund-Mackay
      score). Postoperatively, the patients were treated with nasal irrigation and
      topical steroid spray. RESULTS: Following surgery, the mean computed tomography
      score decreased from preoperative 17.0+/-4.3 to 8.5+/-4.7. Major complication
      occurred in one patient. Nasal mucosal adhesion was the most frequent minor
      complication (5.4%). Nasal polyposis recurred in 78 patients (19.1%), of whom 57
      patients underwent revision surgery. CONCLUSION: Our data show that functional
      endoscopic sinus surgery combined with corticosteroid administration is effective
      in the treatment of nasal polyposis.

PMID- 19155678
TI  - A case of invasive meningioma involving the maxillary sinus.
AB  - Meningiomas account for nearly 15% of primary brain tumors, but extracranial
      meningiomas are very rare. We presented a case of invasive maxillary sinus
      meningioma. A 50-year-old man presented with facial tenderness and severe pain in
      the left cheek. He had a prior surgery for a meningioma in the left frontal lobe
      eight months before. Physical examination and computed tomography showed a mass
      in the left maxillary sinus. Histopathological result of the biopsy obtained via
      the Caldwell-Luc approach was invasive meningioma. The mass was removed with the
      sinus mucosa. The histology of the resected specimen was compatible with invasive
      angioblastic meningioma. Postoperative radiotherapy was administered because of
      residual intracranial tumor. No recurrence was detected over an 11-month follow
      up period.

PMID- 19155679
TI  - [Vascular leiomyoma mimicking a carotid body tumor].
AB  - Vascular leiomyomas are composed of smooth muscle cells and vascular endothelium.
      They are rarely seen in the head and neck region. A 32-year-old woman presented
      with a slowly-growing pulsatile mass in the right upper jugular region.
      Angiography showed a mass in the carotid bifurcation. It was not extensively
      vascularized, but displaced the internal and external carotid arteries. After
      neck exploration, the lesion was totally resected without any complications.
      Histopathologic diagnosis was vascular leiomyoma. No recurrence was detected
      during a two-year follow-up.

PMID- 19155680
TI  - Laryngeal adenoid cystic carcinoma in an adolescent.
AB  - Malignant tumors of the larynx are extremely rare in children and adolescents.
      Adenoid cystic carcinoma accounts for less than 1% of all malignant tumors in the
      larynx. We presented a 16-year-old girl with subglottic adenoid cystic carcinoma,
      whose symptoms of prolonged and exacerbating dyspnea had been attributed to
      asthma at another medical center. Indirect flexible and rigid laryngoscopy
      revealed a smooth mass in the subglottic region occupying 80% of the airway
      passage. The lesion was also confirmed by both CT and MRI. There was no
      lymphadenopathy in the neck. The patient was successfully treated by surgery and
      postoperative radiotherapy. Pathological staging was T4N0M0 according to the
      AJCC, 2003. During six years of follow-up, there was no evidence for local
      recurrence or regional and distant metastasis.

PMID- 19155681
TI  - Management of lingual tonsillar hypertrophy using microdebrider.
AB  - A female patient presented with globus sensation, chronic cough, and choking
      attacks. Endoscopic examination showed lingual tonsillar hypertrophy. Partial
      lingual tonsillectomy was planned. Surgery was performed under local anesthesia
      in the sitting position, with the use of the microdebrider under the guidance of
      an endoscope. The operation was accomplished with minimal bleeding. Surgery was
      very comfortable and easy for both the patient and the surgeon. The microdebrider
      was found to be effective and useful in the management of lingual tonsillar
      hypertrophy.

PMID- 19155682
TI  - Cystic hygroma colli in adults: a report of two cases, one with atypical
      location.
AB  - We presented two adult cases of cystic hygroma colli (CHC), one with atypical
      location. The first patient was a 23-year-old male with CHC located in the
      posterior cervical triangle, its common location in the neck. The latter was a 22
      year-old male whose lesion occupied the submandibular region and extended to the
      skull base. The diagnosis was made by computed tomography, magnetic resonance
      imaging, and fine-needle aspiration biopsy, and confirmed by postoperative
      histopathologic examination. The lesions were surgically removed in both
      patients, and no recurrence was encountered during postoperative 12 and 14
      months, respectively.

PMID- 19155683
TI  - [Tuberculosis-associated immune reconstitution inflammatory syndrome].
AB  - The prognosis of HIV-infected patients has dramatically improved since the advent
      of HAART. The immune recovery associated with HAART may result in immuno
      pathological reactions and clinical deterioration when HAART is initiated in
      patients with tuberculosis (TB). This phenomenon is defined as immune
      reconstitution inflammatory syndrome (IRIS). In this review, we summarise the
      epidemiology, clinical presentations and management of TB-associated IRIS.

PMID- 19155684
TI  - [Informed consent for HIV diagnostic tests: what to do in case of minors].
AB  - AIDS is a clinical picture related to Human Immunodeficiency Virus (HIV)
      infection. In the last 20 years this infection has spread progressively, with
      approximately 2.4 million children under 15 years old now infected. The HIV
      antibody test is generally used to reveal the infection. In most European
      countries the test is voluntary; in Italy, implementation of the test is now
      regulated by Law 135/90. Art. 5 of the law states that the test is voluntary
      while informed consent is obligatory. However, nothing is stated concerning the
      child's consent. By contrast, other Italian laws (e.g., Law 194/78, Law 194/96
      and DPR 309/90) establish that the physician should only accept the wishes of
      minors after first appraising the maturity of the child and his/her age.
      Physicians must inform the minor about testing risks, about the meaning of its
      result, and about the most important aspects of sexual education.. They may then
      decide to inform the parents if they feel that the child would be unable to take
      future decisions in the event of a positive HIV antibody test.

PMID- 19155685
TI  - Etiology of prosthetic joint infections in a tertiary care centre in Italy.
AB  - Prosthetic joint infections (PJIs) represent a severe complication in
      orthopaedics. Coagulase-negative staphylococci (CoNS) and Staphylococcus aureus
      represent the most frequent cause, but Gram-negatives have also been reported.
      With a view to describing the aetiology of PJIs diagnosed from January 2005 to
      September 2007 at S. Corona Hospital in Pietra Ligure, Italy, we conducted
      retrospective analysis of pathogens isolated from PJIs by means of surgical
      specimens, needle aspirates or swabs of fistula (3 samples). During the study
      period 228 PJIs were described and 141 (62%) were microbiologically documented
      and evaluated. Early and delayed infections represented 45% of episodes, while
      late infections were observed in 55%. The aetiology was mono-microbial in 84% of
      cases, and polymicrobial in 16%. CoNS and S. aureus were the most frequently
      isolated pathogens. In early and delayed infections methicillin resistant CoNS
      were 30% and 24%, respectively, while in late infections they were 17%.
      Methicillin-resistant S. aureus was isolated in 13% of early, 22% of delayed and
      15% of late infections. Gram-negatives were described in 16% of episodes without
      differences being found in the three groups. In our report staphylococci
      represented the most frequent cause of PJIs. Methicillin-resistant strains were
      more frequently isolated in early and delayed infections, but their frequency in
      late episodes was not negligible. Polymicrobial infections and Gram-negative
      infections were also frequent.

PMID- 19155686
TI  - Bronchoalveolar lavage as a diagnostic tool in patients with hematological
      malignancies and pneumonia.
AB  - We report our experience concerning bronchoalveolar lavage (BAL) in adult
      patients affected by haematological malignancies. BAL was performed in patients
      with documented pulmonary diseases not responding to empirical antibiotic and
      antifungal therapies. Overall, 25 bronchoscopies were performed in 24 patients.
      This technique led to pathogen identification in 11 out of 24 patients (45
      percent). In particular, we identified four cases of tuberculosis, four of
      aspergillosis, two of pneumocystosis, two bacterial pneumonia and one pneumonia
      sustained by CMV (in two cases, pneumonia was polymicrobial). In three cases,
      where microbiological diagnosis had been obtained by means of other exams (blood
      culture, urinary antigens), BAL negativity allowed us to exclude alternative
      diagnoses. Pulmonary location of haematological disease was diagnosed in seven
      patients. BAL drove a switch therapy in 54 percent of patients. When performed by
      expert operators, BAL is useful and safe also in frail patients, such as those
      affected by onco-haematological malignancies.

PMID- 19155687
TI  - [Off-label antibiotic use: malpractice or good clinical practice?].
AB  - In Italy, off-label drug use has been forbidden since 1998. However, Italian law
      allows off-label treatment for single cases only if treatment is considered
      irreplaceable, and completely under physician responsibility. To assess the
      consequences of such regulations for the infectious diseases specialist, we
      listed the indications of intravenous and oral antibiotics available in our
      hospital pharmacy service, and discussed them in a pool of nine infectious
      diseases specialists. Indications were compared with the recommended treatment of
      major bacterial syndromes as suggested by the major guidelines and textbooks. We
      found that standard treatment for several bacterial infections is off-label. The
      pool of specialists concluded that some off-label use of antibiotics is vital to
      daily practice in infectious diseases. Scientific societies should promote
      guidelines as the standard reference for good clinical practice, which should not
      be based only on the respect of drug labels.

PMID- 19155688
TI  - [Prospective observational study of pneumonia in an Italian hospital].
AB  - A prospective observational study was conducted during a two-year period to
      evaluate the prevalence of hospitalized pneumonia in six hospital units of the
      Bologna S.Orsola-Malpighi hospital (Italy). The selected units were: general
      surgery, general medicine, internal medicine, geriatrics, respiratory
      physiopathology and pneumology, with a total of 205 beds and around 4,800
      admissions per year. Data were collected from the clinical cards and cases of
      pneumonia were distinguished by origin (community-acquired or hospital-acquired
      according to CDC definition), individual and clinical characteristics, and
      aetiology. The study involved 486 cases of pneumonia: 75 hospital-acquired and
      411 community-acquired (84.6%). Patients affected by hospital-acquired pneumonia
      were older (average age 77 years) compared to community-acquired cases (74 years)
      and show a more homogeneous gender distribution (males: 48.0% vs 59.4%). Hospital
      stays (42 vs 21 days) and mortality rates (24.0% vs 11.7%) were significantly
      higher in hospital-acquired pneumonia. The incidence rate of nosocomial pneumonia
      was 7.4 per 1000 hospitalized patients and increased to 17-23 per 1000 in the
      pneumology and respiratory physiopathology units. Only 16.9% of cases had an
      aetiological diagnosis (14.1% community-acquired; 31.8% hospital-acquired); the
      most common isolates were S. aureus and P. aeruginosa. The hospital-acquired
      cases were caused by Gram-negative bacilli more often than the community-acquired
      cases, and infections were more frequently polymicrobial (37.5% vs 3.4%). In
      order to reduce morbidity and mortality due to pneumonia it is important to
      implement prevention measures in the community (i.e. specific vaccination
      campaigns), improve clinical protocols for aetiological diagnosis in hospitalised
      patients and increase epidemiological surveillance of hospital-acquired
      infections.

PMID- 19155689
TI  - [Saccharomyces cerevisiae fungemia associated with multifocal pneumonia in a
      patient with alcohol-related hepatic cirrhosis].
AB  - Saccharomyces cerevisiae is usually considered non-pathogenic and has rarely been
      reported as a cause of fungemia in immunocompromised patients, especially those
      admitted to an intensive care unit or those affected by acquired immune
      deficiency syndrome or under immunosuppressive treatment. In all described cases
      the use of probiotic yeast has been given as the main risk factor. We report a
      case of S. cerevisiae sepsis complicated by pneumonia in a patient affected by
      alcohol-related cirrhosis with no evidence of probiotic drug intake. In this case
      recovery was obtained after a treatment course with liposomal amphotericin B. S.
      cerevisiae should be taken into consideration when sepsis lacks to isolate any
      aetiological agent.

PMID- 19155690
TI  - Retroperitoneal abscess: an uncommon localization of tubercular infection.
AB  - We describe a rare case of a 29-year-old immunocompetent Nigerian male affected
      by an abdominal abscess due to Mycobacterium tuberculosis infection. Diagnosis
      was achieved with cultures from surgical drainage. No pulmonary, renal, or
      gastrointestinal involvement was identified. The patient was successfully treated
      with standard four-drug antitubercular therapy.

PMID- 19155691
TI  - Isolated laryngeal leishmaniasis in an immunocompetent patient: a case report.
AB  - Visceral leishmaniasis, a protozoan disease caused by Leishmania infantum, is
      endemic in the Mediterranean basin, especially southern and Tyrrhenian Italy. Its
      aetiological agent can also sporadically cause isolated laryngeal localization in
      at-risk patients (i.e., heavy smokers, immunocompromised patients). This rare
      localization is often pauci-symptomatic and thus can easily escape diagnosis. A
      case of isolated leishmaniasis limited to the left vocal cord in an
      immunocompetent Italian male without significant risk factors, randomly
      discovered upon histological examination, is described herein. We inquire how
      many patients affected by non-specific symptoms such as dysphonia and live in
      countries where Leishmania infantum infection is reported, could be truly
      affected by Leishmania spp infection.

PMID- 19155692
TI  - [Contribution of paleopathology to defining the pathocoenosis of infectious
      diseases (Part one)].
AB  - Studying the remains of mummies obtained by archaeological research may provide
      key information concerning historical pathocoenosis. Paleopathology makes it
      possible to recognise, characterise and connect different features involved in
      human pathocoenosis, such as epidemiology, in a historical perspective, and
      cultural development, via the introduction of new livestock farming techniques
      and agriculture in general. Several distinct pathologies may produce direct and
      indirect changes in the skeleton of affected individuals. Therefore bone remains
      represent very important sources of information to study such diseases. Changes
      related to trauma and nutrition deficiency as well as secondary signs, induced by
      tuberculosis, brucellosis, leprosy, syphilis, malaria, periostitis and aspecific
      osteomyelitis, persist in bones. In addition, other diseases may cause indirect
      alterations and subsequent secondary bone in the skeleton via different
      mechanisms. A secondary bone dimorphism may be induced by poliomyelitis.
      Aspecific lesions may arise in a skeletal bone and then cause secondary
      alterations in near-bone segments. Reviewing studies of paleopathologic research
      found in the literature, we emphasize the relationship between the appearance of
      major infectious diseases and the development of human activities; whereas it is
      clear that the introduction of livestock farming had a key role in the
      pathocoenosis of distinct infections such as tuberculosis, brucellosis and
      leprosy, some doubts and uncertainty remain in relation to the origin of others
      with epidemiologically important pathologies, such as syphilis.

PMID- 19155708
TI  - 2009 coding and payment changes for physicians.

PMID- 19155709
TI  - Topical Leptospermum honey (Medihoney) in recalcitrant venous leg wounds: a
      preliminary case series.

PMID- 19155710
TI  - Diabetic foot: Charcot neuropathic osteoarthropathy.

PMID- 19155711
TI  - The role of interventional patient hygiene in improving clinical and economic
      outcomes.
AB  - OBJECTIVE: To successfully educate, integrate, and empower nonlicensed personnel
      in the surgical intensive care unit in the use of a skin care protocol to
      maintain and improve skin integrity. DESIGN: Observational intervention study.
      SETTING: Surgical intensive care unit. PATIENTS: Data related to alterations in
      skin integrity were collected over 4 months, representing approximately 2000
      patient-days. A total of 97 specific events representing 121 "areas of concern"
      were identified by nonlicensed personnel. INTERVENTIONS: Nonlicensed staff
      members' knowledge in 6 key areas related to pressure ulcer (PrU) development was
      surveyed before and after implementation of an interventional patient hygiene
      (IPH) program incorporating comprehensive bathing and incontinence protocols. A
      unique point-of-use skin inspection tool was used by nonlicensed personnel to
      communicate areas of concern to licensed personnel (registered nurses [RNs]).
      MAIN OUTCOME MEASURES: Reduction in PrUs and improvement in nonlicensed staff
      knowledge of facility protocols. MAIN RESULTS: Incidence of new PrUs decreased
      from 7.14% at baseline to 0% at the end of the study. Nonlicensed staff knowledge
      increased to 100% in all 6 knowledge areas. CONCLUSION: Implementation of an IPH
      program incorporating comprehensive bathing and incontinence management resulted
      in enhanced communication between nonlicensed staff and RNs as well as improved
      patient outcomes.

PMID- 19155712
TI  - High rate of deficiency in the amino acids tryptophan and histidine in people
      with wounds: implication for nutrient targeting in wound management--a pilot
      study.
AB  - BACKGROUND: Malnutrition resulting from inadequate protein, energy, or
      micronutrient intake has been identified as an independent risk factor for the
      development of pressure ulcers in older adult patients and is associated with
      increased morbidity and death. OBJECTIVE: To assess the relationship between
      albumin, the standard biochemical marker of nutritional adequacy, and amino acid
      status in people with wounds. METHODS: The authors performed tests for serum
      albumin, prealbumin, and amino acid profiles on 18 consecutive hospital patients
      with wounds and 7 patients without wounds. RESULTS: A low level of the essential
      amino acids tryptophan and histidine was a common finding in older people with
      wounds. Of the 18 consecutive wound cases, 16 (88.9%) were found to be deficient
      in tryptophan, histidine, or both. Moreover, levels were generally found to be
      lower than those in the group without wounds. The levels of all other amino acids
      were essentially normal for all patients. Finally, although serum albumin is
      often used as a surrogate marker of amino acid adequacy or nutritional status,
      clinically abnormal albumin had poor specificity (63.2%), poor sensitivity
      (60.7%), and low positive predictive value (70.8%) for the identification of a
      low tryptophan or histidine level. CONCLUSIONS: People with wounds are a
      relatively at-risk group and are likely to be overlooked in terms of
      micronutrient deficiencies, and these findings have important implications in
      terms of potential specific targeting of nutrient supplementation.

PMID- 19155713
TI  - The nursing process and pressure ulcer prevention: making the connection.
AB  - PURPOSE: To provide the wound care practitioner with an understanding of how use
      of the nursing process enhances pressure ulcer prevention. TARGET AUDIENCE: This
      continuing education activity is intended for physicians and nurses with an
      interest in skin and wound care. OBJECTIVES: After reading this article and
      taking this test, the reader should be able to: 1. Describe the use of the
      nursing process for planning, implementing, and evaluating the outcomes of a
      pressure ulcer prevention program. 2. Explain how to use the Braden Scale for
      Predicting Pressure Sore Risk to develop "at risk" nursing diagnoses and to guide
      intervention.

PMID- 19155715
TI  - Monitoring laboratory values: transferrin, C-reactive protein, erythrocyte
      sedimentation rate, and liver function.

PMID- 19155716
TI  - It seems that it was yesterday.

PMID- 19155717
TI  - Aspirations unchanged for the American Journal of Dermatopathology 30 years after
      its founding: a forum for collision of ideas.

PMID- 19155718
TI  - Jacob Henle--a pioneer of dermatopathology.
AB  - Jacob Henle was one of the most important anatomists of all times. He was the
      founder of modern histology and discovered numerous anatomic structures, such as
      Henle's loop in the kidneys and Henle's gland in the conjunctiva of the eyelids.
      Dermatologists know him chiefly for his description of Henle's layer of the inner
      root sheath of the hair follicle. Only few, however, are aware of other
      contributions of Henle to dermatology, such as the first description of Demodex
      folliculorum and, more importantly, the first book devoted to the histopathology
      of the skin. Henle's contributions were significant enough to qualify him as one
      of the foremost pioneers of dermatopathology.

PMID- 19155719
TI  - Visual perception and consciousness in dermatopathology: mechanisms of figure
      ground segregation account for errors in diagnosis.
AB  - Visual perception has been the object of research in psychology for almost a
      century. Little has been written, however, about the effects of perceptive
      phenomena on methods in medicine that utilize interpretation of two-dimensional
      images for diagnosis. Starting from the work by Edgar Rubin in the beginning of
      the last century, this article gives a summary of observations of psychologists
      who investigated the mechanisms of so-called "figure-ground segregation." These
      unconscious mechanisms follow rules that explain why certain structures are
      perceived consciously as a figure, whereas other structures surrounding such a
      figure are neglected and not perceived consciously in detail. Perception of a
      structure as a figure can be due to, for example, a convex shape of its contour,
      proximity of lines around it, closed contours, a simple shape, and attribution of
      meaning to a structure. In examples from the practice of dermatopathology, those
      unconscious mechanisms of figure-ground segregation will be shown to be relevant
      to diagnosis of sections of tissue. The mechanisms help to explain why, for
      example, ill-defined and concave-shaped structures, stromal differences of
      neoplasms, interstitial infiltrates and deposits, and simulators of common
      diseases are often difficult to recognize at first sight. Teachers of
      dermatopathology need to be aware of these unconscious mechanisms of visual
      perception because they explain why novices struggle with certain diagnoses and
      differential diagnoses. Proper instruction about these phenomena, early in the
      process of training, will prevent a student from being frustrated with
      misperceptions.

PMID- 19155720
TI  - Mimicry illuminating pitfalls in histopathologic diagnosis: nutritional
      deficiency-like dermatitis secondary to topical tazarotene and
      keratoacanthomatous pseudocarcinomatous hyperplasia in CD30+ lymphoproliferative
      disorder as illustrative.
AB  - In the course of daily sign-out, histopathologists are confronted with instances
      in which the histopathologic findings may simulate another entity. At times, it
      can be extraordinarily difficult to distinguish the simulacra from the authentic.
      Sometimes this happens because different conditions rarely may show nearly
      identical histopathologic findings. Other times the most prominent
      histopathologic findings are not the diagnostic ones, yet they may closely
      resemble a specific entity that is wholly unrelated to the diagnosis. An example
      of each of these types of mimicry is presented in conjunction with a discussion
      of the associated pitfalls in diagnosis. Last, a brief discussion of different
      categories of histopathologic mimicry is presented.

PMID- 19155721
TI  - An assist to the next (10th) edition of Lever's Histopathology of the Skin.
AB  - Lever's Histopathology of the Skin, regarded as the gold standard textbook in the
      field of dermatopathology, claims to cut a swath through the discipline. In the
      last two editions, however, it appears to be declining in its overall scientific
      quality and academic mentality by failing to include different points of view set
      forth by other authors. Some ideas of a single author, coupled with appropriate
      references, are offered by me now for consideration for inclusion in the next
      (10th) edition of Lever's text.

PMID- 19155722
TI  - Discordant architectural and cytological features in cutaneous sebaceous
      neoplasms--a classification dilemma: report of 5 cases.
AB  - The authors present a series of 5 cases of cutaneous sebaceous neoplasms having
      "benign" architectural features (symmetry, sharp circumscription, smooth borders,
      pseudoencapsulation) but which simultaneously displayed atypical cytology
      including abnormal mitoses, high mitotic rates, and moderate-to-striking
      pleomorphism including bizarre cells. The patients included 4 females and 1 male,
      ranging in age at diagnosis from 49 to 72 years. All presented with a small
      solitary nodule (6-9 mm) on the forehead (2), chest wall (1), occiput (1), and
      shoulder (1). The lesions were surgically excised. There were no recurrences on
      follow-up ranging from 16 to 148 months (average 77 months). In none of the
      patients was there a history of internal malignancy before or after diagnosis of
      the cutaneous neoplasms. Of 3 tumors assessed immunohistochemically for the
      expression of DNA mismatch repair gene proteins, only one showed loss of MLH1
      expression. This was the only tumor to contain numerous tumor-infiltrating
      lymphocytes. Our report emphasizes the existence of rare sebaceous tumors that,
      despite a deceptively bland architectural appearance, discordantly exhibit a
      range of atypical cytological features more characteristic of either low-grade or
      even high-grade carcinomas. Whether such tumors should be classified as
      sebaceomas with atypia or sebaceous carcinomas is unclear at present. Further
      studies are needed to confirm their seemingly benign course as identified in this
      report, as are further investigations to clarify their association with Muir
      Torre syndrome.

PMID- 19155723
TI  - A distinct entity in the spectrum of the CD30+ cutaneous lymphoproliferative
      diseases: oligolesional nodules with pseudoepitheliomatous hyperplasia followed
      by spontaneous resolution.
AB  - Pseudoepitheliomatous hyperplasia (PEH) in biopsies of CD30+ anaplastic large
      cell lymphoma (ALCL) is present infrequently and is of unknown prognostic value
      and significance. Our goal was to review the clinicopathologic features of cases
      of ALCL with PEH, study their course, and review the literature on the subject.
      Biopsy specimens of all cases of CD30+ lymphoproliferative disorders (59) were
      retrieved from the files of Yale Dermatopathology Laboratory over a 17-year
      period and reviewed. We identified 4 cases of ALCL (7%) exhibiting prominent PEH.
      All 4 patients presented with 1 or 2 nodules. In 2 patients, the lesions
      spontaneously regressed within a few months after initial diagnosis. One patient
      chose to have an excision in which only a small number of CD30+ cells were
      present. We were unable to obtain follow-up for the fourth patient. In the
      spectrum of CD30+ lymphoproliferative disorders, cases of ALCL with PEH are
      infrequent. In addition to the 4 cases described here, in our review of the
      literature we found 35 cases of ALCL with PEH. Most of these patients present
      with 1 or a few lesions. In the majority of these cases, the lesions started
      showing evidence of clinical spontaneous regression and even complete resolution
      within a few months of initial diagnosis. The clinicopathologic correlation
      between ALCL and PEH has not been emphasized. Because most of these cases follow
      a relatively benign clinical course, we recommend a more conservative approach in
      the clinical management of these patients.

PMID- 19155724
TI  - Dermatomyofibroma: clinicopathologic and immunohistochemical analysis of 56 cases
      and reappraisal of a rare and distinct cutaneous neoplasm.
AB  - Dermatomyofibroma represents a rare and distinct benign cutaneous mesenchymal
      neoplasm of fibroblastic/myofibroblastic differentiation. A series of 56 cases of
      dermatomyofibroma has been analyzed to further characterize the clinicopathologic
      spectrum of this entity. Forty patients were female and 8 were male (gender was
      unknown in 8 cases). Patients' age ranged from 3 to 51 years (mean 30.8 years,
      median 30 years). Interestingly, 6 patients were younger than 16 years, and in
      this age group, 3 male and 3 female patients, respectively, were noted. The
      shoulder (13 cases) was the anatomic site most commonly affected, followed by the
      upper arm (7 cases), the neck (6 cases), the thigh (6 cases), the chest wall (4
      cases), the back (3 cases), the axillary fold (2 cases), the abdominal wall (2
      cases), and 1 case each was seen on the forearm, the buttock, and the popliteal
      fossa (exact anatomic location was unknown in 10 cases). One patient presented
      with 2 lesions arising simultaneously on both shoulders. Histologically, an ill
      defined, plaque-like dermal neoplasm of varying cellularity was seen in all
      cases, composed of bland spindle-shaped tumor cells often oriented parallel to
      the overlying epidermis. An infiltration of superficial part of the subcutis was
      seen in 23 cases, and in 6 cases, deeper parts of the subcutis were involved by
      often perpendicular growing bands of neoplastic cells. Immunohistochemically,
      tumor cells in 11 of 48 cases tested stained positively for alpha-smooth muscle
      actin, and a focal expression of this marker was noted in 20 cases. In addition,
      a focal expression of CD34 was seen in 10 of 45 cases tested. Follow-up
      information was available in 38 cases (range from 3 to 156 months, median 34
      months), and despite marginal or incomplete excision in 17 cases, none of the
      cases recurred. Dermatomyofibroma represents a benign
      fibroblastic/myofibroblastic dermal neoplasm.

PMID- 19155725
TI  - Reparative perineural hyperplasia: a series of 10 cases.
AB  - Healing wounds are commonly examined by pathologists at the time of reexcision of
      skin tumors to ensure complete removal of the lesion. In addition to searching
      for residual tumor, possible perineural invasion must be assessed. During routine
      examination of reexcision specimens, 10 cases of prominent perineural
      proliferation were seen associated with fine nerves in the mid or deep dermis.
      The process showed a concentric cellular proliferation with no, or only limited,
      nuclear hyperchromasia or pleomorphism. In a number of cases,
      immunohistochemistry was essential to exclude the possibility of malignant
      perineural invasion or other mimics of this process such as reexcision perineural
      invasion. The term reparative perineural hyperplasia is proposed for this entity,
      which is important for pathologists to be aware of to avoid misdiagnosis.

PMID- 19155726
TI  - Investigation of the inflammatory mechanisms in alopecia areata.
AB  - We aimed to investigate the profile of the inflammatory infiltrate in lesional
      and nonlesional tissue in alopecia areata (AA) and look for possible associations
      between inflammatory mechanisms, neuropeptide expressions, and various clinical
      features. Twenty-four patch-type AA patients were included. Forty-eight lesional
      and nonlesional skin samples were stained immunohistochemically with antibodies
      for CD1a, CD3, CD4, CD8, CD20, CD57 (for natural killer cells), mast cell
      tryptase, nerve growth factor receptor (NGFR), and substance P (SP). Various
      clinical findings were recorded. Psychological distress levels and stress-related
      hormones were measured. Lesional skin showed statistically more CD3(+), CD8(+),
      and CD57(+) lymphocytes, mast cells, Langerhans cells, and more prominent
      immunoreactivities of NGFR and SP (P < 0.003). Most nonlesional skin showed
      CD3(+) and CD57(+) cells, mast cells, and NGFR(+) nerve fibers. NGFR and SP, and
      SP and perivascular mast cell infiltrates were correlated, whereas peribulbar
      mast cells and anagen follicle counts were inversely correlated in nonlesional
      skin (P < 0.05). Near half of the patients' distress levels were high. No
      relationship among biochemical, psychological, and clinical parameters could be
      shown. AA may involve the entire skin in which lesions occur as a result of local
      T cell-mediated cytotoxic inflammatory response initiated by Langerhans cells and
      mast cells activated via neuropeptides.

PMID- 19155727
TI  - Dermatomyositis: a clinicopathological study of 40 patients.
AB  - The histopathology of cutaneous lesions of dermatomyositis (DM) may be
      indistinguishable from acute cutaneous lesions of systemic lupus erythematosus
      (SLE). Misreported or incomplete clinical information may result in a
      clinicopathologic discrepancy and a delay in making a correct diagnosis of DM.
      The aim of this study was to systematically characterize the histopathologic
      findings of cutaneous lesions of DM and to determine if skin biopsy specimens of
      DM and SLE could be distinguished by light microscopic examination. Biopsies from
      40 patients diagnosed with DM at the Wake Forest University School of Medicine
      from 1994 to 1999 were reviewed. The histological features by light microscopy
      were graded in a systematic fashion. We then assessed whether the cutaneous
      pathological changes of DM could be distinguished from those of SLE. Ten biopsy
      specimens each of DM and SLE (matched for anatomical site and lesion morphology)
      were randomized. Histological grading was performed in a blinded fashion, as was
      a histopathologic diagnosis (DM versus SLE). The most consistent histological
      findings of DM included increased dermal mucin, vacuolar alteration of the basal
      cell layer, and mild-to-moderate mononuclear cell inflammatory infiltrates. Our
      results show that the histological grading of SLE skin biopsies was nearly
      identical to that of DM. The correct histopathologic diagnosis of DM or SLE was
      made in 11 of the 20 skin biopsies without clinical information. Despite the
      limitations of our small sample size, these findings suggest that acute cutaneous
      lesions of SLE cannot be distinguished from DM. Clinicopathologic correlation is
      important for making a diagnosis of DM or SLE.

PMID- 19155728
TI  - Fibroblasts from normal skin of a tuberous sclerosis patient show upregulation of
      mTOR pathway.
AB  - Skin lesions are one of the characteristic features in tuberous sclerosis (TS), a
      neurocutaneous disorder caused by mutation of 1 of 2 tumor suppressor genes,
      encoding hamartin and tuberin. So far, however, studies on skin abnormalities
      present in TS patients are very few and do not contribute to the knowledge of the
      disease. In our current work, we cultured fibroblasts from healthy skin of a TS
      patient and evaluated upregulation of pathways found to be implicated in
      progression of TS tumors. We found that even healthy skin fibroblasts show
      upregulation of S6 ribosomal protein.

PMID- 19155729
TI  - Symplastic glomus tumor: a case report.
AB  - Symplastic glomus tumors are defined as glomus tumors with a high-grade nuclear
      pleomorphism in the absence of any other malignant features, such as large size,
      deep location, infiltrative growth, mitotic activity, or necrosis. Only 11 cases
      have been reported so far in the English literature. It could be a challenge for
      pathologists who have no experience with it because the tumor can show marked
      nuclear atypia and pleomorphism. Despite its high nuclear grade, a symplastic
      glomus tumor itself has a benign biologic behavior. Hereby, the authors report a
      case of a symplastic glomus tumor on the right index finger tip of a 44-year-old
      woman with a literature review.

PMID- 19155730
TI  - CD4+, CD56+ mycosis fungoides: case report and review of the literature.
AB  - This case report details an 85-year-old woman who presented with mycosis
      fungoides (MF), clinical stage 1A. Bilateral lesions on the upper thighs were
      responsive to topical steroid therapy. Biopsies showed band-like dermal
      infiltrates of medium-sized lymphocytes with marked epidermotropism, including
      large intraepidermal lymphocytes with nuclear convolutions, consistent with MF.
      Immunohistochemical staining revealed that the lesional cells were CD56+, but
      unlike the case in previous reports of CD56+ MF, they also expressed CD4 and T
      cell intracellular antigen 1 and did not express CD8. To our knowledge, this is
      the first description of a case of MF with a CD4+, CD8-, CD56+, T-cell
      intracellular antigen 1-positive immunophenotype. At 85 years of age, the patient
      is older than all previously described patients with CD56+ MF. Despite an
      immunophenotype observed more commonly in aggressive forms of cutaneous T-cell
      lymphoma, the clinical presentation is that of typical MF. The patient presented
      with limited disease and after 12 months of follow-up has not progressed beyond
      stage 1A.

PMID- 19155731
TI  - Granulomatous pigmented purpura: an unusual histological variant.
AB  - Pigmented purpuric dermatoses (PPDs) tend to vary clinically, yet share a similar
      histology. Granulomas are only rarely seen, with 4 prior reported cases,
      designated granulomatous pigmented purpura. Historically, granulomatous pigmented
      purpura has been seen in Asians. In this article, we report the case of a 42-year
      old, white female with granulomatous pigmented purpura, the fifth such reported
      case in the literature. Histopathological examination revealed a granulomatous
      dermatitis with eosinophils, extravasated erythrocytes, melanophages, and
      vascular proliferation. These findings were consistently reported on subsequent
      biopsy 6 months later. This case illustrates a rare histological finding in PPDs.
      Medications associated with PPD are reviewed and the patient's use of mesalamine
      and balsalazide for ulcerative colitis are deemed potential triggers, given their
      relative similarity to aspirin, a known trigger of PPD. Although other
      granulomatous processes must be excluded in such patients, one must consider the
      possibility of granulomatous pigmented purpura in the appropriate setting.

PMID- 19155732
TI  - Primary cutaneous signet-ring cell melanoma with pseudoglandular features,
      spindle cells and oncocytoid changes.
AB  - The authors report a 69-year-old man with a primary nodular malignant melanoma on
      the shoulder showing unusual histological features. It mostly consisted of
      markedly neoplastic melanocytes, which exhibited abundant clear cytoplasm
      compressing the nuclei to the periphery, resulting in a signet-ring appearance.
      In other areas of the melanoma, there were focally desmoplastic and
      pseudoglandular patterns and oncocytoid changes. Immunohistochemical studies
      showed that the tumor cells were uniformly positive only for S-100 protein and
      vimentin. Signet-ring cell melanoma is a rare histopathological variant of
      malignant melanoma with only a few described cases. To the best of our knowledge,
      this is the first case reporting a combination of the signet-ring cell melanoma
      with desmoplastic, pseudoglandular, and oncocytoid features.

PMID- 19155733
TI  - Signet-ring cell dermatofibroma.
AB  - Dermatofibroma or cutaneous fibrous histiocytoma is a common benign skin lesion
      with multiple, distinct histologic variants, including cellular, aneurismal,
      epithelioid, atypical, lipidized "ankle-type," palisading, and cholesterotic.
      Although dermatofibromas are considered benign neoplasms, certain variants
      including cellular and aneurismal ones have shown to have a notable tendency to
      locally recur after excision. Indeed, although extremely rarely, metastases have
      been associated with the cellular and aneurysmal/atypical variants. Signet-ring
      cells are formed by cytoplasmic accumulations of various substances that push the
      nucleus toward the cellular border. The finding of signet-ring cells in a skin
      neoplasm always raises the suspicion of metastatic adenocarcinoma, although a
      number of reports have shown their occurrence in primitive cutaneous neoplasms as
      well. Signet-ring cell formation, however, has never been described in
      dermatofibroma. We present, for the first time, a new, distinctive variant of
      dermatofibroma, so-called signet-ring cell dermatofibroma, in a 16-year-old man
      with a slowly growing skin tumor on the lateral side of his right leg. Histologic
      examination demonstrated a striking signet-ring cell appearance of most of the
      cells in an otherwise fibrohistiocytic looking proliferation. Histochemical and
      immunohistochemical stainings confirmed the diagnosis of dermatofibroma. The
      phenomenon described in this case enlarges the histologic spectrum of cutaneous
      fibrous histiocytoma and may cause substantial differential diagnostic problems.

PMID- 19155734
TI  - Metastatic interdigitating dendritic cell sarcoma masquerading as a skin primary
      tumor: a case report and review of the literature.
AB  - We report an unusual case of a lymph node interdigitating dendritic cell sarcoma
      (IDCS), metastatic to skin, in a 73-year-old patient. The patient initially
      presented as having a primary skin tumor with lymph node metastasis. The
      metastatic IDCS was initially read as an atypical fibroxanthoma. However, the
      morphology seen on the lymph node excision, paired with immunohistochemistry and
      electron microscopy studies, was diagnostic for an IDCS. Additional
      immunohistochemistry was performed on the shave biopsy, confirming that the skin
      tumor was a metastasis. IDCS is a rare tumor that belongs to the histiocytic and
      dendritic cell group of tumors. Diagnosing this entity is difficult without the
      aid of ancillary testing such as immunohistochemistry and electron microscopy. In
      the workup of a spindle cell neoplasm, IDCS should be included in the
      differential diagnosis.

PMID- 19155735
TI  - Classifying neoplasms with sebaceous differentiation--a reviewer's comments.

PMID- 19155736
TI  - A case of sebaceoma with extensive apocrine differentiation.

PMID- 19155737
TI  - Re: CD117 immunoreactivity in atypical fibroxanthoma.

PMID- 19155738
TI  - Osteoclast-type giant cells accompanying cutaneous squamous cell carcinoma.

PMID- 19155739
TI  - Focal epithelial hyperplasia: polymerase chain reaction amplification as a
      differential diagnosis tool.

PMID- 19155743
TI  - Three steps forward, two steps back in helping people with dementia.

PMID- 19155744
TI  - Meta-analysis comparing different behavioral treatments for late-life anxiety.
AB  - OBJECTIVE: To evaluate the efficacy of different types of behavioral treatments
      for geriatric anxiety (cognitive behavior therapy [CBT] alone, CBT with
      relaxation training [RT], and RT alone). METHOD: The authors compared effect
      sizes from 19 trials. Analyses were based on uncontrolled outcomes (comparing
      posttreatment and pretreatment scores) and effects relative to control conditions
      on both anxiety and depressive symptoms. RESULTS: Treatments for older adults
      with anxiety symptoms were, on average, more effective than active control
      conditions. Effect sizes were comparable to those reported elsewhere for CBT for
      anxiety in the general population or for pharmacotherapy in anxious older adults.
      CBT (alone or augmented with RT) does not seem to add anything beyond RT alone,
      although a direct comparison is challenging given differences in control
      conditions. Effects on depressive symptoms were smaller, with no differences
      among treatment types. CONCLUSION: Results suggest that behavioral treatments are
      effective for older adults with anxiety disorders and symptoms. Results must be
      interpreted with caution given the limitations of the literature, including
      differing sample characteristics and control conditions across studies.

PMID- 19155745
TI  - Your brain on Google: patterns of cerebral activation during internet searching.
AB  - OBJECTIVE: Previous research suggests that engaging in mentally stimulating tasks
      may improve brain health and cognitive abilities. Using computer search engines
      to find information on the Internet has become a frequent daily activity of
      people at any age, including middle-aged and older adults. As a preliminary means
      of exploring the possible influence of Internet experience on brain activation
      patterns, the authors performed functional magnetic resonance imaging (MRI) of
      the brain in older persons during search engine use and explored whether prior
      search engine experience was associated with the pattern of brain activation
      during Internet use. DESIGN: Cross-sectional, exploratory observational study
      PARTICIPANTS: The authors studied 24 subjects (age, 55-76 years) who were
      neurologically normal, of whom 12 had minimal Internet search engine experience
      (Net Naive group) and 12 had more extensive experience (Net Savvy group). The
      mean age and level of education were similar in the two groups. MEASUREMENTS:
      Patterns of brain activation during functional MRI scanning were determined while
      subjects performed a novel Internet search task, or a control task of reading
      text on a computer screen formatted to simulate the prototypic layout of a
      printed book, where the content was matched in all respects, in comparison with a
      nontext control task. RESULTS: The text reading task activated brain regions
      controlling language, reading, memory, and visual abilities, including left
      inferior frontal, temporal, posterior cingulate, parietal, and occipital regions,
      and both the magnitude and the extent of brain activation were similar in the Net
      Naive and Net Savvy groups. During the Internet search task, the Net Naive group
      showed an activation pattern similar to that of their text reading task, whereas
      the Net Savvy group demonstrated significant increases in signal intensity in
      additional regions controlling decision making, complex reasoning, and vision,
      including the frontal pole, anterior temporal region, anterior and posterior
      cingulate, and hippocampus. Internet searching was associated with a more than
      twofold increase in the extent of activation in the major regional clusters in
      the Net Savvy group compared with the Net Naive group (21,782 versus 8,646 total
      activated voxels). CONCLUSION: Although the present findings must be interpreted
      cautiously in light of the exploratory design of this study, they suggest that
      Internet searching may engage a greater extent of neural circuitry not activated
      while reading text pages but only in people with prior computer and Internet
      search experience. These observations suggest that in middle-aged and older
      adults, prior experience with Internet searching may alter the brain's
      responsiveness in neural circuits controlling decision making and complex
      reasoning.

PMID- 19155746
TI  - Anxiety symptoms and objectively measured sleep quality in older women.
AB  - OBJECTIVES: Few studies have examined the association between anxiety symptoms
      and objectively measured sleep quality in older adults. The authors determined
      this association in a large cohort of very old community-dwelling women. DESIGN:
      Cross-sectional. SETTING: Participants' homes, sites of the Study of Osteoporotic
      Fractures. PARTICIPANTS: Three thousand forty women (mean age: 83.6 years)
      enrolled in a prospective study of aging. MEASUREMENTS: Participants completed
      the Goldberg Anxiety Scale (ANX), the 15-item Geriatric Depression Scale (GDS),
      and > or = 3 nights of actigraphy--a method of measuring sleep by recording wrist
      movement with a device called an actigraph. Elevated anxiety symptoms were
      defined as ANX > or = 6. Elevated depressive symptoms were defined as GDS > or =
      6. RESULTS: Participants' mean ANX score was 1.4 (standard deviation: 2.2); 9.2%
      (N = 280) had ANX > or = 6. Elevated anxiety symptoms were associated with
      greater odds of poor sleep efficiency (odds ratio [OR]: 1.73, 95% confidence
      interval [CI]: 1.34, 2.23) and time awake after sleep onset (OR: 1.64, 95% CI:
      1.27, 2.11). Associations remained after adjustment for GDS > or = 6, antianxiety
      medications, and other potential confounders (sleep efficiency OR: 1.50, 95% CI:
      1.15, 1.97; time awake after sleep onset OR: 1.33, 95% CI: 1.01, 1.75). Anxiety
      symptoms were not associated with other sleep parameters. CONCLUSION: Findings
      suggest that elevated anxiety symptoms are independently associated with poor
      objectively measured sleep efficiency and elevated sleep fragmentation in very
      old women, after accounting for significant depressive symptoms, medical
      comorbidities, and use of antianxiety medications.

PMID- 19155747
TI  - Depressive symptoms moderate the influence of the apolipoproteine epsilon4 allele
      on cognitive decline in a sample of community dwelling older adults.
AB  - OBJECTIVES: The apolipoproteinE epsilon4 (APOE epsilon4) allele and a history of
      depression are each separate risk factors for cognitive decline (CD). However,
      little research has investigated whether a history of depression influences the
      relationship between APOE epsilon4 and CD. The present study examined whether
      depressive symptoms had greater influence on subsequent CD among participants
      with APOE epsilon4 than those without the allele. DESIGN: Prospective 6-year
      longitudinal study. SETTING: Community in-home interviews. PARTICIPANTS: A
      biracial sample of community dwelling older adults (N = 1,992) from the Duke
      Established Populations for Epidemiologic Studies of the Elderly (EPESE).
      MEASUREMENTS: Data were drawn from Waves 1 to 3 of the EPESE, which were
      conducted 6 years apart. Cognitive functioning and depressive symptoms were
      assessed at both waves, and APOE genotyping was completed during the Wave 3
      assessment. RESULTS: Regression analyses revealed that depressive symptoms and
      the APOE epsilon4 allele independently predicted CD. Importantly, the influence
      of depressive symptoms on CD was greater for individuals with the APOE epsilon4
      allele compared with those without the allele. CONCLUSION: Depressive symptoms
      and the APOE epsilon4 allele are independent contributors to CD. Moreover, the
      influence of depressive symptoms on CD is greater among individuals with the APOE
      epsilon4 allele. Depression and the APOE epsilon4 allele may act together in
      disrupting neurological functioning, which may in turn lower an individual's
      cognitive reserve capacity. Given the efficacious treatments currently available
      for depression, future research should investigate the extent to which
      interventions for depression may reduce the risk for subsequent CD.

PMID- 19155748
TI  - Melatonin fails to improve sleep or agitation in double-blind randomized placebo
      controlled trial of institutionalized patients with Alzheimer disease.
AB  - OBJECTIVES: Patients with Alzheimer dementia often display both agitated behavior
      and poor sleep. Given that the disease is often associated with low endogenous
      levels of melatonin, exogenous melatonin administration may lead to improvements
      in sleep and agitation. DESIGN: Randomized, placebo-controlled study. SETTING:
      Nursing homes in San Diego, CA, metropolitan area. PARTICIPANTS: Subjects were
      patients with probable Alzheimer disease. INTERVENTION: Melatonin (8.5 mg
      immediate release and 1.5 mg sustained release) (N = 24) or placebo (N = 17)
      administered at 10:00 P.M. for 10 consecutive nights. The protocol consisted of
      baseline (3 days), treatment (10 days), and posttreatment (5 days) phases.
      MEASUREMENTS: Sleep was measured continuously using actigraphy. Agitation was
      rated using both the Agitated Behavior Rating Scale and the Cohen-Mansfield
      Agitation Inventory. Treatment effects were examined both across the 24-hr day
      and separately by nursing shift. RESULTS: There were no significant effects of
      melatonin, compared with placebo, on sleep, circadian rhythms, or agitation.
      CONCLUSION: : This study failed to find a beneficial effect of exogenous
      melatonin, consistent with a number of other studies. The lack of efficacy may be
      related to the absence of a true treatment effect or to the superphysiologic dose
      of melatonin used.

PMID- 19155749
TI  - Memantine dosing in patients with dementia.
AB  - OBJECTIVES: To examine the dosing of memantine in patients with dementia admitted
      to an inpatient geriatric psychiatry ward and review the published literature
      regarding the pharmacologic and clinical need to dose adjust memantine. METHOD: A
      retrospective study was conducted involving patients, admitted over a 2-year
      period, with a diagnosis of dementia and receiving memantine. Published clinical
      trials, pharmacokinetic studies, and clinical trial registry data were used to
      investigate relationships among dose, efficacy, and side effects. RESULTS: Of the
      70 patients comprising the study sample, 27% were not prescribed appropriate
      doses of memantine at the time of admission. Notably, 60% of those patients who
      should had memantine renally dose-adjusted were not prescribed the adjusted dose.
      Trial and pharmacokinetic data support the need to renally adjust memantine.
      CONCLUSION: Appropriate dosing of memantine in patients with dementia is
      important in an effort to maximize the medication's safety and efficacy.

PMID- 19155750
TI  - Current attitudes regarding treatment of agitation and psychosis in dementia.

PMID- 19155751
TI  - Gastroenteropancreatic neuroendocrine tumors in patients with HIV infection: a
      trans-Atlantic series.
AB  - BACKGROUND: Non-AIDS-defining cancers are an important problem in HIV-infected
      patients. The occurrence of neuroendocrine (NE) tumors in sites other than the
      lung and skin has not been well characterized in the setting of concurrent HIV
      infection. METHODS: HIV-positive patients with biopsy-confirmed NE tumors
      localized to the gastrointestinal tract were identified based on the personal
      archives of the authors. A retrospective chart review was performed, and data
      regarding demographics, HIV status, presenting symptoms and signs, diagnostic
      work-up, therapeutic interventions, and outcome were extracted. RESULTS: We
      identified 4 adult patients, mean age 42 years (range: 37-47) infected with HIV,
      who developed NE tumors originating in their gastrointestinal tact. They had only
      moderate immunosuppression with a median CD4 count of 497 cells/mm (range: 182
      1100) and chronic HIV infection (2-15 years duration). Symptoms at presentation
      were nonspecific, including abdominal pain, diarrhea, weight loss, and rectal
      bleeding. A specialized diagnostic work-up was required, including serum
      chromogranin and urinary 5-hydroxyindoleacetic acid levels, colonoscopy,
      radioactive isotope scans, and the demonstration of NE differentiation in
      procured pathologic material. The spectrum of tumors ranged from benign (typical
      carcinoid) to highly aggressive neoplasms (NE carcinoma). Treatment with
      octreotide, surgical resection, or systemic chemotherapy provided effective
      symptomatic relief and was associated with a favorable outcome, despite
      metastases in 2 patients. CONCLUSIONS: These cases serve to broaden the spectrum
      of neoplasms that may be encountered in the current HIV era, and illustrate the
      difficulty in establishing the diagnosis of NE tumors in the context of HIV
      infection.

PMID- 19155752
TI  - Iodine deficiency disorders in the iodine-replete environment.
AB  - BACKGROUND: Iodine deficiency disorders (IDD) constitute significant public
      health problems in parts of the world with poor iodine nutrition, but have been
      eradicated in North America and other regions. We herein report 3 cases of IDD,
      which occurred in women living in iodine-replete environments. METHODS: The
      clinical presentation, biochemical findings, and radiological features of the
      patients were analyzed and presented in 3 case reports. The radiological features
      are illustrated in sonographic and scintigraphic images. A literature review and
      discussion, which highlight the risk factors, pathogenesis, ancillary
      investigations, and rational treatment of iodine deficiency goiter and
      hypothyroidism are provided. RESULTS: All 3 patients were young women, aged 24 to
      38 years, who had goiter. Two of them presented with goitrous hypothyroidism.
      Radioactive iodine scintigraphy showed a characteristic finding of diffusely
      increased uptake (in the absence of clinical and biochemical evidence of
      hyperthyroidism). This scintigraphic pattern was found to be pathognomonic.
      Dietary iodine supplementation alone resulted in complete remission of IDD in the
      subjects, including the 2 patients with hypothyroidism. CONCLUSION: IDD can occur
      in iodine-replete environments. A high index of suspicion is needed to recognize
      these cases. It is pertinent that the correct diagnosis be made to avoid
      unwarranted life-long thyroxine therapy in patients presenting with goiter and
      hypothyroidism, which is easily treatable with iodized salt. These cases
      underscore the need for considering iodine deficiency in the etiologic diagnosis
      of goiter and hypothyroidism, even in iodine-sufficient regions.

PMID- 19155753
TI  - The impact of declining clinical autopsy: need for revised healthcare policy.
AB  - In Western countries, autopsy rates for patients deceased in hospitals have
      dropped to record lows, while the average frequency of major errors in clinical
      diagnoses has more than doubled during the same time period. Meanwhile, the
      Institute of Medicine and the U.S. Department of Health and Human Services have
      called attention to the high frequency of errors affecting patient safety,
      bringing the issue of public safety to the forefront of public health concerns.
      Although autopsies represent a vital tool for the acquisition of new medical
      knowledge and for medical quality assurance, health care professionals, insurers,
      and politicians apparently have not chosen the right approach to solve the
      problem of declining autopsy rates. The present article reviews the current
      status of clinical autopsies and addresses causes and consequences of their
      neglect and appeal the urgent need to revise the policy for clinical autopsy.

PMID- 19155754
TI  - Saving president Lincoln: an update for clinicians.

PMID- 19155755
TI  - Abdominal wall and intraperitoneal abscesses complicating Aspergillus peritonitis
      in peritoneal dialysis.

PMID- 19155757
TI  - Neuro-ophthalmology and neuro-otology.

PMID- 19155758
TI  - Electrodiagnostic assessment in optic nerve disease.
AB  - PURPOSE OF REVIEW: Complementary electrophysiological techniques can be useful in
      detecting and localizing dysfunction within the visual pathway. Recent
      developments are outlined in the context of neuro-ophthalmology. RECENT FINDINGS:
      The relationship between nerve fibre layer anatomy and the pattern visual evoked
      potential has been addressed, correlating axonal loss with visual pathway
      dysfunction. Longitudinal assessment of multiple sclerosis patients has defined
      parameters affecting the utility of the pattern visual evoked potential as an
      outcome measure in potential treatment trials. In optic nerve tumours, the
      pattern visual evoked potential may help identify and monitor the disorder. The
      pattern electroretinogram assesses retinal ganglion cell function and can
      identify macular dysfunction, possibly mimicking optic nerve disease clinically.
      The spatial extent of macular dysfunction can be assessed using the multifocal
      electroretinogram. Objective visual evoked potential assessment of visual acuity
      can be important in the management of nonorganic visual loss. The multifocal
      visual evoked potential is a relatively new technique that is attracting
      increasing research interest, particularly as a measure of visual field loss, but
      has yet to be established as a reliable diagnostic tool. SUMMARY:
      Electrophysiology, combined with clinical and imaging investigations, is a
      powerful diagnostic and monitoring tool. Macular dysfunction can mimic optic
      nerve disease in the absence of fundus abnormality.

PMID- 19155759
TI  - Primary optic nerve tumours.
AB  - PURPOSE OF REVIEW: Advances have been made in the treatment of primary optic
      nerve tumours. With a focus on the last few years' publications, recommendations
      for clinical management are being developed. RECENT FINDINGS: In low-grade optic
      nerve glioma, two divergent developments are observed: an increasing reluctance
      in treating such tumours because of reports about treatment toxicity (secondary
      tumours, moyamoya syndrome) and a steady and marked improvement both in
      radiotherapy and chemotherapy. Many reports on beneficial effects of radiotherapy
      on optic nerve meningioma have been published. Radiotherapy does not only
      preserve but in many cases even improves or restores visual function and has,
      therefore, become the therapy of choice in this tumour. SUMMARY: Establishing a
      treatment plan in cases of optic nerve glioma is difficult and must be made on an
      individual basis. Although both chemotherapy and radiotherapy can stabilize and
      sometimes improve vision in progressive tumours, chemotherapy is the preferred
      modality in children younger than 9 years and in patients with neurofibromatosis
      1. In functionally progressive optic nerve meningioma with useful visual
      function, multifractioned stereotactic conformal radiotherapy is the treatment of
      choice.

PMID- 19155760
TI  - Rehabilitation of hemianopia.
AB  - PURPOSE OF REVIEW: Homonymous hemianopia is the commonest form of acquired
      homonymous visual field defect; the usual causes are stroke, head injury and
      intracranial tumours. This impairment can affect a variety of cognitive visual
      functions, including visual search, safe navigation through changing environments
      and reading. A number of rehabilitative techniques have been tried with varying
      degrees of success. They broadly fall into three main groups: optical therapies,
      in which the damaged visual field is brought into view by the use of optical
      devices; eye movement-based therapies, in which the damaged visual field is more
      effectively sampled with compensatory or adaptive eye movements; and visual field
      restitution therapies, in which vision in the damaged field is itself improved.
      These techniques all rely on mass practice. This review provides an up-to-date
      summary of these approaches. RECENT FINDINGS: All of the three main approaches to
      rehabilitation of homonymous visual field defect have been pursued in recent
      years and all appear capable of providing a moderate amount of 'real-world'
      improvement to patients. Controversy still reigns over the mechanism of action of
      all but the optical methods. Patients have to practice for many hours to feel the
      benefit of all of these techniques, with the eye movement-based therapies
      requiring the least amount of exposure. SUMMARY: The evidence base for these
      types of behavioural therapy is getting stronger all the time. Future studies
      that take on the difficult task of controlling for placebo effects will allow
      patients' subjective ratings of success to be used as a convincing outcome
      measure. Without doubt, the literature would also benefit from bigger studies
      that include more patients; however, one could argue that given the clear
      negative effect that homonymous visual field defect has on patients' lives, these
      therapies should be more widely available already.

PMID- 19155761
TI  - Transient ischaemic attack: clinical relevance, risk prediction and urgency of
      secondary prevention.
AB  - PURPOSE OF REVIEW: Transient ischaemic attack (TIA) is increasingly recognized as
      a harbinger of stroke and an important opportunity for secondary prevention. We
      have reviewed recent evidence on the burden of TIA and prediction and prevention
      of stroke in the acute phase. RECENT FINDINGS: Although recent data on the
      incidence and prevalence of TIA are lacking, available data suggest that the
      burden of TIA is higher than previously estimated and may be expected to increase
      with the ageing of the population. Prospective prognostic studies have shown that
      the early risk of stroke after TIA is approximately 5% at 7 days and 10-15% at 90
      days depending on clinical settings and study methodology. This risk can be
      reliably predicted by risk scores based on clinical features (the ABCD system),
      TIA aetiology and findings on brain imaging, although the optimal combined
      prognostic strategy is uncertain because the interaction between individual
      predictors is not established. Studies of the urgent assessment and initiation of
      secondary prevention in specialist centres suggest that the early risk of stroke
      after TIA can be reduced by up to 80%. SUMMARY: The risk of stroke after TIA is
      considerable. However, recent advances have shown that this risk can be predicted
      for individuals and substantially reduced by appropriate secondary prevention
      measures.

PMID- 19155762
TI  - Predicting tissue outcome in stroke: new approaches.
AB  - PURPOSE OF REVIEW: Multimodal MRI provides powerful tools to study acute stroke
      pathophysiology and to guide stroke therapy. In particular, the perfusion
      diffusion mismatch has been hypothesized as a target for treatment beyond the 3 h
      time window. Studies of infarct progression and of tissue oxygen metabolism
      suggest that infarct risk is extremely heterogeneous across the diffusion and
      perfusion lesion. The review describes techniques to more accurately image and
      model penumbral infarct risk. RECENT FINDINGS: Methods assessing oxygen supply by
      either blood oxygen level-dependent contrast MRI or models of oxygen delivery
      capacity may improve the detection of tissue-at-risk. Informatics approaches
      integrate acute multimodal and follow-up images from large patient cohorts into
      models of infarct progression. When applied to subsequent acute image data, these
      techniques may assign infarct risks to mismatch tissue. Recent studies suggest
      that such estimates of tissue infarct risk may detect treatment-related risk
      reduction in small patient cohorts. SUMMARY: MRI methods may detect markers of
      metabolic derangement in ischemia, facilitating the detection of penumbral
      tissue. Predictive models extend the current perfusion-diffusion mismatch concept
      by estimating voxel-based risk estimates. With future developments, predictive
      models may support advanced prognostic support and cost-effective testing of
      novel stroke therapies.

PMID- 19155763
TI  - Lifestyle and stroke risk: a review.
AB  - PURPOSE OF REVIEW: In recent years, many epidemiological studies have given new
      insights into old and new lifestyle factors that influence the risk of
      cerebrovascular events. In this review, we refer to the most important articles
      to highlight recent advances, especially those important for stroke prevention.
      RECENT FINDINGS: This review focuses on the most recent studies that show the
      association of environmental factors, nutrition, alcohol, tobacco, education,
      lifestyle and behavior with the risk of vascular disease, including ischemic
      stroke and cerebral hemorrhage. The link between air pollution and stroke risk
      has become evident. Low education levels and depression are established as risk
      factors. This is also true for heavy alcohol consumption, although moderate
      drinking may be protective. Active and passive smoking are independent risk
      factors, and a smoking ban in public places has already reduced cardiovascular
      events in the short term. Physical activity reduces stroke risk; overweight
      increases it. However, clinical trials to assess the effect of weight reduction
      on stroke risk are still lacking. Fruits, vegetables, fish, fibers, low-fat dairy
      products, potassium and low sodium consumption are known and recommended to
      reduce cardiovascular risk. Data on omega 3 fatty acid, folic acid and B vitamins
      are inconsistent, and antioxidants are not recommended. SUMMARY: Stroke can be
      substantially reduced by an active lifestyle, cessation of smoking and a healthy
      diet. Both public and professional education should promote the awareness that a
      healthy lifestyle and nutrition have the potential to reduce the burden of
      stroke.

PMID- 19155764
TI  - Symptomatic intracranial stenosis: best medical treatment vs. intracranial
      stenting.
AB  - PURPOSE OF REVIEW: The high risk of stroke and death in patients with symptomatic
      intracranial stenosis despite medical therapy has spurred interest in
      endovascular treatment approaches. RECENT FINDINGS: Three stents have been
      designed for the treatment of intracranial stenosis, and two, the Wingspan and
      Neurolink Stent Systems, have been evaluated in single-arm trials. The trials and
      two prospective registries evaluating the Wingspan Stent System suggest that
      stenting is most likely to be beneficial in patients with the highest risk of
      stroke on medical therapy, namely those with 70-99% stenosis. SUMMARY: Randomized
      treatment trials comparing stenting with medical therapy in symptomatic
      intracranial stenosis need to target the patients at highest risk of recurrent
      vascular events on medical therapy. Such trials are in progress. Ongoing trials
      in Asia are also assessing medical therapies, including cilostazol, in patients
      with intracranial stenosis.

PMID- 19155765
TI  - To stent or not to stent: stent-protected percutaneous angioplasty versus
      endarterectomy post hoc analyses.
AB  - PURPOSE OF REVIEW: To summarize randomized controlled trials on endarterectomy
      and stenting of symptomatic carotid stenoses and identify factors that impact the
      decision for either therapeutic method. RECENT FINDINGS: Carotid endarterectomy
      is currently the standard method of secondary stroke prevention in patients with
      moderate-to-severe symptomatic carotid artery stenosis. Carotid artery stenting
      has emerged as a therapeutic alternative. The noninferiority to endarterectomy
      with respect to periprocedural safety has not been proven, but the long-term
      efficiency of stroke prevention after successful stenting is very similar,
      despite the observation that the rate of restenosis after stenting is
      significantly higher than after endarterectomy. Thus, the key difference between
      stenting and surgery is periprocedural safety. From subgroup analysis of the
      Stent-protected Percutaneous Angioplasty versus Endarterectomy data, it emerges
      that elderly patients are at higher than average periprocedural risk of
      ipsilateral stroke on the day of stenting but not if treated by surgery. This
      finding is an argument for catheter access problems through tortuous vessels with
      severe atherosclerosis in the proximal carotid artery of elderly patients as the
      source of periprocedural risk of stenting. SUMMARY: Carotid artery stenting for
      secondary stroke prevention is a method with unproven noninferiority of
      periprocedural safety but similar long-term efficiency compared to
      endarterectomy.

PMID- 19155766
TI  - Revival of extra-intracranial bypass surgery.
AB  - PURPOSE OF REVIEW: Extra-intracranial bypass surgery has regained significant
      relevance over the past years. The aim of this review is to highlight the current
      indications and recent developments in this field. RECENT FINDINGS: One main
      indication today is stroke prevention by flow augmentation in the setting of
      chronic cerebral hemodynamic ischemia which is defined as a combination of steno
      oclusive cerebrovascular disease, inadequate collateralization, and loss of
      cerebrovascular reserve capacity. Another indication is flow replacement in the
      context of therapy of complex aneurysms and skull base tumors. The herein
      proposed revival of bypass surgery is due to the progress in individualized,
      tailored therapeutic strategies as well as patient selection. Furthermore, we
      witness a dramatic improvement in the surgical technique as well as the
      development of a broad armamentarium of different bypass types, which today allow
      tailored revascularization strategies for our patients. Finally, the revival of
      bypass surgery is also explained by significant technical progress. One of the
      major developments within the last years is the Excimer laser-assisted
      nonocclusive anastomosis technique which allows performance of an anastomosis
      without the need for temporary clipping, thus dramatically reducing the risk for
      perioperative ischemia in bypass surgery. SUMMARY: Extra-intracranial bypass
      surgery has become a central part of a highly specialized, interdisciplinary
      strategy for the therapy of complex aneurysms and skull base tumors.

PMID- 19155768
TI  - Current world literature.

PMID- 19155767
TI  - Factors affecting outcome after endovascular treatment of intracranial aneurysms.
AB  - PURPOSE OF REVIEW: This brief review highlights some factors affecting the short
      term and long-term outcomes after endovascular treatment (EVT) of patients with
      intracranial aneurysms. RECENT FINDINGS: The principal procedural risks
      associated with EVT are symptomatic thromboembolic events affecting 2.4-5.2% of
      treatments, and aneurysm perforation which occurs in 0.5-2.4% of the patients
      with unruptured aneurysms and 2.3-6.5% of patients with subarachnoid haemorrhage.
      The risk of subsequent aneurysm recurrence requiring retreatment is about 10% and
      does not negate the morbidity advantage (relative to surgical clipping) of the
      initial EVT. This risk is about three-fold greater in aneurysms with a neck width
      more than 4 mm and sac maximum diameter greater than 10 mm. The incidence of
      rebleeding after EVT is 0.11-0.32% per annum and is probably lower if EVT
      achieves complete occlusion. SUMMARY: EVT dramatically reduces the risk of
      rebleeding in patients with subarachnoid haemorrhage. Treatment risks and rates
      of incomplete occlusions are increased in ruptured in comparison with unruptured
      aneurysms. Large aneurysms have higher risk of procedural thromboembolism,
      incomplete treatment and rate of recurrences with strong interdependence between
      these variables. The low risk of rebleeding in patients with subarachnoid
      haemorrhage is probably increased in incompletely treated aneurysms and in
      patients revealing aneurysm growth over time.

PMID- 19155769
TI  - Prevention of mother-to-child HIV transmission using 3-drug combination
      antiretroviral treatment: observational cohort in clinical practice setting in
      India.

PMID- 19155770
TI  - Is dual therapy with raltegravir and protease inhibitors a feasible option in
      rescue strategy in HIV-1 infection?

PMID- 19155771
TI  - Does early antiretroviral treatment prevent liver fibrosis in HIV/HCV-coinfected
      patients?

PMID- 19155772
TI  - Attitudes towards circumcision among Chinese men.

PMID- 19155773
TI  - European Society of Hypertension Working Group on Obesity Obesity-induced
      hypertension and target organ damage: current knowledge and future directions.

PMID- 19155774
TI  - Does dietary starch raise blood pressure?

PMID- 19155775
TI  - Prehypertension causes a mounting problem of harmful cardiovascular disease risk
      in young adults.

PMID- 19155776
TI  - Measuring blood pressure: who and how?

PMID- 19155777
TI  - Ultrasonographic investigation of the mechanics of vulnerable atherosclerotic
      plaques: significance of the volume strain.

PMID- 19155778
TI  - Antihypertensive treatment and risk of cardiovascular complications: is the cure
      worse than the disease?

PMID- 19155779
TI  - Health behaviour patterns in relation to hypertension: the English Longitudinal
      Study of Ageing.
AB  - OBJECTIVE: Clinical guidelines emphasize that hypertensive individuals should be
      encouraged to maintain healthy lifestyles with respect to smoking, physical
      activity, alcohol consumption and diet. We assessed health behaviours in a large
      sample of older hypertensive individuals, and tested whether medication for
      hypertension leads to compensatory increases in cardiovascular risk behaviours.
      METHODS: Analysis of wave 1 of the English Longitudinal Study of Ageing,
      involving 5231 men and 6292 women aged at least 50 years. We analysed the
      prevalence of smoking, heavy drinking, sedentary behaviour and vigorous physical
      activity in relation to self-reported hypertension, controlling for age, sex,
      socioeconomic status, comorbidity (coronary heart disease, diabetes, arthritis),
      impairments of mobility, activities of daily living and depression. RESULTS: The
      prevalence of self-reported hypertension was 37.8%, and 77% of hypertensive
      participants were prescribed medication. Hypertensive participants were less
      likely to smoke than normotensive ones (14.8 vs. 19.7%), with reduced odds of
      smoking [odds ratio (OR) 0.72, 95% confidence intervals (CI) 0.56-0.83] after
      adjusting for covariates. Hypertensive individuals were more likely to be heavy
      drinkers (OR 1.34, CI 1.10-1.62), to be sedentary (OR 1.14, CI 1.02-1.27), and
      not engage in vigorous physical activity (OR 0.84, CI 0.75-0.94). There was no
      evidence for risk compensation in medicated hypertensive individuals compared
      with unmedicated ones. CONCLUSION: Smoking rates are low among hypertensive
      individuals, but the patterns of alcohol consumption and physical activity are
      suboptimal. Compensatory increases in risky behaviours appear not to be present
      in medicated individuals. There is considerable scope for advice and counselling
      to older hypertensive individuals to improve patterns of health behaviour.

PMID- 19155781
TI  - Circulating carotenoid concentrations and incident hypertension: the Coronary
      Artery Risk Development in Young Adults (CARDIA) study.
AB  - BACKGROUND: Several epidemiological studies have demonstrated that carotenoid
      concentrations relate inversely to cardiovascular disease incidence. Thus, we
      examined the association of circulating carotenoids with hypertension, a major
      macrovascular disease risk factor. METHODS: Black and White men and women in the
      Coronary Artery Risk Development in Young Adults Study, aged 18-30 years at
      recruitment (1985-1986) from four US cities, were investigated over 20 years. At
      years 0, 7, and 15, we determined the relationships of the sum of four serum
      carotenoids (alpha-carotene, beta-carotene, lutein/zeaxanthin, cryptoxanthin) and
      of lycopene with incident hypertension using proportional hazards regression
      models. RESULTS: In 4412 participants, year 0 sum of four carotenoids was
      significantly inversely associated with 20-year hypertension incidence after
      adjustment for baseline systolic blood pressure and other confounding factors
      (relative hazard per SD increase of sum of four carotenoids: 0.91; 95% confidence
      interval = 0.84-0.99). The inverse relationships persisted in time-dependent
      models updating year 0 sum of four carotenoids with year 7 and year 15 values
      (relative hazard per SD increase of sum of four carotenoids: 0.84; 95% confidence
      interval = 0.77-0.92). Lycopene was unrelated to hypertension in any model.
      CONCLUSION: Those individuals with higher concentrations of sum of carotenoids,
      not including lycopene, generally had lower risk for future hypertension.

PMID- 19155780
TI  - Dietary starch intake of individuals and their blood pressure: the International
      Study of Macronutrients and Micronutrients and Blood Pressure.
AB  - OBJECTIVE: Data from the Multiple Risk Factor Intervention Trial show an
      independent direct association between starch intake and blood pressure in
      American men at higher risk of coronary heart disease. Cross-sectional data from
      the International Study of Macronutrients and Micronutrients and Blood Pressure
      (INTERMAP) were used to assess relations of dietary starch intake to blood
      pressure in men and women from four countries. METHODS: Data include 83 nutrients
      from four multipass 24-h dietary recalls and two timed 24-h urine collections;
      eight blood pressure readings; and questionnaire data, for 4680 participants aged
      40-59 years from 17 population samples in Japan, People's Republic of China,
      United Kingdom, and United States of America. RESULTS: In multiple linear
      regression analyses--adjusted for urinary sodium, urinary potassium, consumption
      of alcohol, cholesterol, saturated fatty acids, polyunsaturated fatty acids,
      calcium, and other variables--starch intake higher by two standard deviations
      (14.1% kJ) was associated with systolic/diastolic blood pressure differences of 
      1.0/-0.9 mmHg (P = 0.09, P < 0.05). Results were similar with additional control
      for fiber, magnesium, or phosphorus; reduced to -0.5/-0.7 mmHg (P = 0.47, P =
      0.13) with separate adjustment for vegetable protein. Findings were similar for
      men analyzed separately, for American men, and for American men at higher
      coronary heart disease risk. CONCLUSION: Our findings indicate that--if any-
      relations of starch intake to blood pressure are modestly inverse. Current
      dietary guidelines for hypertension prevention and control remain relevant.

PMID- 19155782
TI  - The environmental and genetic evidence for the association of hyperlipidemia and
      hypertension.
AB  - OBJECTIVE: Both hyperlipidemia and hypertension are the risk factors for coronary
      heart disease. Although studies have shown that there is an association between
      plasma lipid and blood pressure levels, the association of hyperlipidemia and
      hypertension is still not well established. The present study was undertaken to
      compare the differences in several environmental and genetic factors between
      hyperlipidemia and hypertension in the Guangxi Hei Yi Zhuang population. METHODS:
      A total of 1669 participants were surveyed by a stratified randomized cluster
      sampling. Information on environmental factors was collected with standardized
      questionnaires. Genotyping of angiotensin-converting enzyme, angiotensinogen,
      angiotensin receptor 2, apolipoprotein (apo) A-I, apoB, apoE, cholesteryl ester
      transfer protein, G-protein beta-3 subunit, hepatic lipase, lipoprotein lipase,
      microsomal triglyceride transfer protein, regulator of G-protein signaling 2, and
      sterol regulatory element-binding protein-2 was also performed. RESULTS: There
      were 358 (21.45%) participants with isolated hyperlipidemia, 257 (15.40%) with
      isolated hypertension, 189 (11.32%) with both conditions, and 865 (51.83%)
      normals. Hyperlipidemia was positively correlated with age, BMI, alcohol
      consumption, total energy and total fat intake, apoE, and microsomal triglyceride
      transfer protein genotypes, and negatively associated with total dietary fiber
      intake, apoA-I, and lipoprotein lipase genotypes. Hypertension was positively
      correlated with male sex, age, hyperlipidemia, total energy, total fat, and
      sodium intake, apoE, angiotensin receptor 2, and microsomal triglyceride transfer
      protein genotypes, and negatively associated with education level, total dietary
      fiber intake, angiotensin-converting enzyme, apoA-I, and lipoprotein lipase
      genotypes. CONCLUSION: These findings suggest that hyperlipidemia and
      hypertension have many common risk factors. Hyperlipidemia is associated with
      hypertension in many aspects.

PMID- 19155783
TI  - Frequency of diarrhoea as a predictor of elevated blood pressure in children.
AB  - BACKGROUND: Diarrhoeal illness is a major public health problem for children
      worldwide, particularly among developing countries, and is a proxy condition for
      severe dehydration. It has been hypothesized that severe dehydration in the first
      6 months of life could be associated with increased blood pressure later in life.
      This study aimed to explore whether frequency of diarrhoea is associated with
      elevated blood pressure in children in a setting with a high incidence of
      diarrhoeal disease. METHODS: The present study is a cross-sectional study of
      blood pressure among children from a longitudinal child diarrhoeal disease cohort
      in Lima, Peru. From 2001 to 2006, daily diarrhoeal surveillance was made.
      Children were revisited in 2006 and blood pressure was measured. Diarrhoeal
      exposures were evaluated in terms of total number of diarrhoea days, number of
      episodes of diarrhoea, persistent diarrhoeal episodes and by the quartiles of
      daily incidence and episode incidence of diarrhoea. RESULTS: The overall
      incidence of diarrhoeal episodes at age under 1 year was 4.35 (95% confidence
      interval: 3.79-4.98) and under 5 years was 2.80 (95% confidence interval: 2.69
      2.92). No association was observed between the total number of diarrhoeal days,
      diarrhoeal episodes or diarrhoeal incidence rates with childhood blood pressure.
      There was weak evidence that hospital admission due to severe dehydration in the
      first year of life showed a gradient towards an increase in both, systolic and
      diastolic blood pressure. CONCLUSION: In the first study to date to examine the
      association in a setting with a high incidence of diarrhoeal disease, diarrhoeal
      frequency did not show an association with increased blood pressure. Our
      observations of elevated levels of blood pressure among those admitted into
      hospitals in the first year of life are in line with the original hypothesis of
      dehydration in early infancy and high blood pressure. However, the effect of
      episodes of severe dehydration on later blood pressure remains uncertain.

PMID- 19155784
TI  - Twenty-year cardiovascular and all-cause mortality trends and changes in
      cardiovascular risk factors in Gubbio, Italy: the role of blood pressure changes.
AB  - AIMS: In an observational population study that lasted 20 years, the
      relationships between mortality trends and changes in cardiovascular risk factor
      levels were examined. METHODS AND RESULTS: In the town of Gubbio, in central
      Italy, population surveys for measurement of cardiovascular risk factors were
      performed 20 years apart. In a subset of the initial cohort (1927 men and 2333
      women), mortality data were collected for 20 years. Cardiovascular risk factor
      levels were compared in individuals in the same age range (20-79 years) examined
      at the initial survey (1927 men and 2333 women) and at the final survey (1761 men
      and 2055 women). Age-adjusted rates significantly declined, by 28% among men and
      51% among women, for all causes of death, and by 50% among men and 71% among
      women for cardiovascular disease deaths. Declines were observed in the levels of
      systolic blood pressure, serum cholesterol, resting heart rate, smoking habits,
      BMI, plasma glucose (the latter two only in women) and the estimated
      cardiovascular risk, together with increases in serum high-density lipoprotein
      cholesterol and in the proportion of treated and controlled hypertensive
      patients. CONCLUSION: Although similar but less impressive changes were recorded
      in Italy at large, the existence of the observational study in Gubbio might have
      motivated the general population and the medical profession towards actions
      promoting general health.

PMID- 19155785
TI  - Use of automated office blood pressure measurement to reduce the white coat
      response.
AB  - OBJECTIVE: To examine the possibility of reducing the white coat response using
      an automated sphygmomanometer designed for office use, the BpTRU. Consecutive
      patients referred from physicians in the community to an ambulatory blood
      pressure (ABP) monitoring unit in an academic hospital were included in the
      study. PARTICIPANTS AND METHODS: A total of 309 patients referred for diagnosis
      or management of hypertension were studied. Differences between mean awake ABP
      and BP readings taken by the patient's own physician using a manual
      sphygmomanometer or the automated BpTRU device with the patient resting alone in
      the ABP monitoring unit were compared. RESULTS: BP recorded in the examining room
      using an automated device (132 +/- 19/75 +/- 12) was similar to the mean awake
      ABP (134 +/- 12/77 +/- 10) with both values being lower (P < 0.001) than the BP
      recorded on a routine visit to the patient's own family physician (152 +/- 18/87
      +/- 11). The coefficient of correlation between the systolic/diastolic ABP and
      the automated office BP (r = 0.62/0.72) was higher (P < 0.001) than with the
      family physician's manual BP (r = 0.32/0.48). The prevalence of white coat
      hypertension in untreated patients (n = 146) was significantly (P < 0.001) lower
      with automated office BP (16%) compared with the routine family physician BP
      (55%). CONCLUSION: The white coat response associated with office BP measurements
      can be virtually eliminated by recording BP with the automated BpTRU device with
      patients resting alone in a quiet examining room.

PMID- 19155786
TI  - Nurse-recorded auscultatory blood pressure at a single visit predicts target
      organ changes as well as ambulatory blood pressure.
AB  - AIM: To determine whether high-quality nurse-recorded auscultatory blood pressure
      (BP) values obtained at a single visit predict cardiovascular target organ
      changes as closely as ambulatory BP measurements. METHODS: In a randomly selected
      population sample (n = 458, 21% receiving antihypertensive treatment;
      approximately 40% hypertensive), we compared high-quality single visit nurse
      recorded auscultatory BP values to same-day 24-h ambulatory BP in their ability
      to predict multiple target organ changes [left ventricular mass index (LVMI),
      left ventricle (LV) mean wall thickness (MWT), early-to-late transmitral velocity
      ratios (E/A), (echocardiography); log of urinary albumin-to-creatinine ratios
      (log ACR) (24-h urine samples); large artery dysfunction [carotid-femoral pulse
      wave velocity (PWV) and central augmentation index (Alc) (applanation
      tonometry)]. RESULTS: Nurse-recorded systolic BP (SBP) measurements obtained at a
      single visit were as closely associated with LVMI (r = 0.44), LV MWT (r = 0.44),
      E/A (r = -0.55), log ACR (r = 0.20), PWV (r = 0.62) and AIc (r = 0.41) (P <
      0.0001 for all relations) as was 24-h SBP (LVMI; r = 0.33, LV MWT; r = 0.37, E/A;
      r = -0.35, log ACR; r = 0.24, PWV; r = 0.41, and AIc; r = 0.18, P < 0.001 for all
      relations) and either day or night SBP. On multivariate regression analysis with
      both nurse-recorded SBP and 24-h SBP in the same model, nurse-recorded SBP was
      independently associated with LVMI (P = 0.006), LV MWT (P = 0.03), E/A (P <
      0.02), PWV (P < 0.0001) and AIc (P = 0.0002), and 24-h SBP was independently and
      positively associated with log ACR (P < 0.005), and PWV (P = 0.01). CONCLUSION:
      One or more, high-quality single visit nurse-recorded auscultatory BP
      measurements may be equally as effective as ambulatory BP in predicting target
      organ damage in a population sample of African ancestry.

PMID- 19155787
TI  - Association of UCP2 and UCP3 polymorphisms with heart rate variability in
      Japanese men.
AB  - OBJECTIVES: The mitochondrial uncoupling proteins UCP2 and UCP3 are implicated in
      energy metabolism and regulation of reactive oxygen species, which are closely
      involved in autonomic nervous system function. Heart rate variability (HRV)
      reflects cardiac autonomic regulation and has been used to evaluate dysfunction
      of the autonomic nervous system in hypertension and cardiovascular diseases. We
      examined the association between polymorphisms in the UCP2 and UCP3 genes and HRV
      in healthy young Japanese men. METHODS: The 45 bp insertion/deletion polymorphism
      in exon8 of UCP2 and the -55C/T polymorphism in the UCP3 promoter region were
      genotyped (n = 255). Cardiac autonomic function was evaluated by power spectral
      analysis of HRV during supine rest and in a standing position. Low-frequency
      (<0.15 Hz) and high-frequency (>0.15 Hz) components of HRV were quantified by
      frequency domain analysis. RESULTS: The I/I genotype of the UCP2 45 bp
      insertion/deletion polymorphism was associated with relatively higher blood
      pressure and HRV sympathetic indices (low frequency percentage and low
      frequency:high frequency ratio) at supine rest. For the -55C/T polymorphism of
      UCP3, individuals carrying the -55T allele had significantly lower HRV
      sympathetic indices, but higher HRV parasympathetic indices (high frequency and
      high frequency percentage), than carriers of the C/C genotype at standing. Both
      UCP2 and UCP3 polymorphisms were significantly associated with a third-degree
      family history of hypertension, diabetes, and obesity. Additionally, carriers of
      the UCP2 45 bp I allele -UCP3 -55C/C combined genotype had the lowest HRV
      sympathetic and the highest HRV parasympathetic indices at standing among the
      combined genotypes. CONCLUSION: UCP2 and UCP3 polymorphisms were associated with
      HRV in young and healthy states, suggesting a significant relationship between
      autonomic cardiovascular regulation and UCP2/UCP3 polymorphisms.

PMID- 19155788
TI  - Study of the genetic variability of ZAC1 (PLAGL1) in French population-based
      samples.
AB  - OBJECTIVES: ZAC1 (zinc finger protein regulating apoptosis and cell cycle arrest)
      is a member of the new subfamily of zinc-finger transcription factors, designated
      as PLAG (pleomorphic adenoma gene) family. The ZAC1 gene is maternally imprinted
      and is linked to developmental disorders such as growth retardation and transient
      neonatal diabetes mellitus. We wanted to assess whether the genetic variability
      of the ZAC1 gene was associated with anthropometric (weight, BMI, waist-to-hip
      ratio) or biochemical (plasma lipid, insulin, glucose levels, blood pressure
      level) phenotypes. METHODS: We selected 37 independent SNPs (single nucleotide
      polymorphisms) or tagSNPs in the ZAC1 locus from the literature and several
      databases and, based on the linkage disequilibrium map, identified 27 independent
      SNPs. Those 27 SNPs were genotyped in a French population-based sample (n =
      1155). Associations with a P value lower than 0.0019 (Bonferroni correction) were
      considered significant. RESULTS: We found that women carrying the T allele of
      rs9403542 had lower waist-to-hip ratio (P = 0.0006) than women with the CC
      genotype. Also, men bearing the T allele of rs13218225 had lower systolic (P =
      3.6 x 10(-5)) and diastolic (P = 4.1 x 10(-4)) blood pressure than GG men. As a
      consequence, the adjusted (for age, smoking habit, alcohol consumption, physical
      activity level and BMI) odds ratio (95% confidence interval) of hypertension for
      T allele carrier men was 0.55 [0.35-0.86], P = 0.009. We genotyped two other
      independent samples (MONICA Toulouse, n = 1130 and MONICA Strasbourg, n = 1048)
      for rs9403542 and rs13218225 but we could not confirm these associations.
      CONCLUSION: We found no evidence that polymorphisms in ZAC1 might influence
      anthropometric, biochemical or clinical parameters in French individuals.

PMID- 19155789
TI  - Correlation between augmentation index and pulse wave velocity in rabbits.
AB  - PURPOSE: Pulse wave velocity (PWV) is a direct measure of large arterial
      stiffness. Augmentation index (AIx) is a surrogate measure of arterial rigidity
      that could be affected by the ventricular ejection and peripheral haemodynamics
      in addition to the properties of large arteries. In clinical studies, it is still
      controversial whether PWV depends on AIx or not. We investigated a relationship
      between PWV and AIx in young normal rabbits when mean arterial pressure (MAP)
      level was altered using vasoactive drugs. MATERIALS AND METHODS: Pulse waves were
      simultaneously recorded in the ascending, proximal and distal abdominal aortas in
      response to intravenous infusion of angiotensin II or sodium nitroprusside in
      fifteen normal rabbits anaesthetized with pentobarbital sodium. Changes in
      intravascular diameters were measured using an intravascular ultrasound imaging
      system in the proximal thoracic and proximal abdominal aortas to determine
      pressure-strain elastic modulus (Ep). RESULTS: PWV from the ascending aorta to
      the bifurcation of the common iliac arteries and AIx at the ascending aorta were
      changed with MAP level in response to vasoactive drugs. Significant and positive
      correlation was observed between PWV and MAP. AIx was correlated significantly
      with systolic, diastolic and mean arterial pressures. PWV and AIx showed
      significant and positive correlation mainly with Ep in the proximal thoracic and
      proximal abdominal aortas, respectively. There was significant correlation
      between PWV and AIx (r = 0.66, P < 0.001). CONCLUSION: AIx was changed
      dependently on PWV when the MAP level was changed with vasoactive drugs, which
      was partly associated with the change in Ep.

PMID- 19155791
TI  - Hyperglycemia alters renal cell responsiveness to pressure in a model of
      malignant hypertension.
AB  - OBJECTIVE: Poor glycemic control contributes to development of diabetic
      nephropathy. However, for a majority of clinical situations, the mechanisms
      responsible for high glucose-induced aggravation of renal tissue injury are not
      fully elucidated. We investigated responsiveness to pressure of various renal
      cell subsets subjected to hyperglycemic environment in an in-vitro model of
      malignant hypertension. METHODS: Rat renal mesangium, epithelium and endothelium
      were exposed to high glucose-containing medium for 10 days and then subjected to
      high hydrostatic pressure for 1 h to simulate the incidence of malignant
      hypertension. In some cultures, renin-angiotensin system was experimentally
      suppressed prior to pressure application. Proliferation, apoptosis, intrarenal
      p53, H2O2 and angiotensin-II synthesis were subsequently assessed. RESULTS: By
      contrast to cultures not exposed to high glucose, in all hyperglycemic cells p53
      expression, angiotensin-II synthesis and apoptosis were increased, whereas
      proliferation depressed, irrespective of pressure enforcement. H2O2 release was
      enhanced by high pressure per se, and increased further following exposure to
      high glucose. In all diabetic cultures, inhibition of p53 by a specific inhibitor
      pifithrin concomitantly significantly decreased apoptosis. CONCLUSION:
      Hyperglycemic environment alters responsiveness of renal cells to in-vitro
      simulation of malignant hypertension. The main consequence of either malignant
      hypertension or hyperglycemia is exaggerated apoptosis. However, the operating
      mechanisms differ: Malignant hypertension stimulates renal cell apoptosis via
      increased angiotensin-II, whereas hyperglycemia elicits apoptosis via augmented
      p53. By contrast to pressure-induced excessive proliferation of normoglycemic
      cells, hyperglycemia prohibits elevated proliferation in response to pressure.
      Angiotensin-II production is maximally augmented by hyperglycemic environment and
      is not stimulated further by pressure application.

PMID- 19155792
TI  - Development of cardiovascular disease due to renal insufficiency in male sheep
      following fetal unilateral nephrectomy.
AB  - BACKGROUND: Renal insufficiency is associated with the development of
      cardiovascular disease. OBJECTIVES: This study investigated whether reduced fetal
      renal mass resulted in renal insufficiency, hypertension, cardiac dysfunction and
      whether these changes progressed with age. METHODS AND RESULTS: Fetal
      uninephrectomy was performed at 100-day gestation (term, 150 days) and studies
      performed in male sheep from 6 weeks to 24 months of age. Renal function declined
      with age in sham animals as demonstrated by increasing plasma creatinine levels
      and urinary excretion of albumin. The age-related decline in renal function was
      exacerbated in animals that had undergone fetal uninephrectomy. Evidence of renal
      insufficiency was indicated from as early as 6 weeks of age with elevations in
      plasma creatinine (Ptreatment < 0.001), urea (Ptreatment < 0.001) and sodium
      (Ptreatment < 0.05) levels in uninephrectomized lambs as compared with sham
      animals. At 6 months, urinary albumin excretion (P < 0.001) was increased and
      urinary sodium excretion (P < 0.001) decreased in the uninephrectomized animals.
      By 24 months, renal function had deteriorated further with significant
      progression of albuminuria (P(treatment x age) < 0.001). Elevation of mean
      arterial pressure (approximately 15 mmHg) was associated with significantly
      increased cardiac output, stroke volume and plasma volume at 6 months; arterial
      pressure (approximately 27 mmHg) had increased further in uninephrectomized
      animals at 24 months and was driven by increased total peripheral resistance.
      Cardiac functional reserve (dobutamine challenge) was reduced in
      uninephrectomized animals at 6 and 24 months of age (Ptreatment < 0.001), and
      this was associated with left ventricular enlargement (P < 0.001) and reduced
      fractional shortening (P < 0.01). CONCLUSION: Fetal uninephrectomy causing a
      reduction in nephron endowment results in an accelerated age-related decline in
      renal function. This is associated with an early onset of elevated blood pressure
      and impairments in cardiac structure and function.

PMID- 19155790
TI  - Stroke risk and antihypertensive drug treatment in the general population: the
      Japan arteriosclerosis longitudinal study.
AB  - OBJECTIVE: To evaluate the association between stroke risk and blood pressure
      (BP) levels with regard to the usage of antihypertensive medications. METHODS:
      From the Japan arteriosclerosis longitudinal study, 11,371 participants from the
      four population-based cohort studies (aged 40-89) were followed up for a mean of
      9.5 years. A Poisson regression model, adjusting for possible confounding
      factors, was used to investigate the risk of first stroke among six BP-based
      categories (BP defined according to recent guidelines), in relation to the use of
      antihypertensive medications. RESULTS: There were 324 incident cases of first
      stroke. Among untreated groups, the relative hazard increased linearly with the
      elevation of BP grade (trend P = 0.0001). The untreated group with normal BP had
      a significantly higher stroke risk [relative hazard 2.09, 95% confidence interval
      1.09-4.01] than the untreated group with optimal BP. There was no stepwise
      increase in stroke risk observed among treated groups (trend P = 0.1). The stroke
      risk among treated groups, even among those with optimal BP (relative hazard
      4.10, 95% confidence interval 1.17-14.4), was significantly higher than that in
      the untreated groups with the same BP level. CONCLUSION: Treated individuals with
      optimal BP had a higher stroke risk than untreated ones with optimal BP.
      Healthcare providers need to be vigilant for residual cardiovascular risks in
      treated hypertensive patients.

PMID- 19155793
TI  - Association of plasma cardiotrophin-1 with stage C heart failure in hypertensive
      patients: potential diagnostic implications.
AB  - Cardiotrophin-1 is a cytokine that induces hypertrophy and dysfunction in
      cardiomyocytes and has been shown to be increased in hypertensive patients. The
      objective of this study was to evaluate the association of cardiotrophin-1 with
      heart failure (HF) in hypertensive patients and its usefulness as a biomarker of
      stage C heart failure. Hypertensive patients without cardiac abnormalities (stage
      A, n = 64), with left ventricular hypertrophy (LVH) (stage B, n = 58), and with
      left ventricular hypertrophy and clinical manifestations of chronic heart failure
      (stage C, n = 39) were studied. Plasma cardiotrophin-1 was measured by an enzyme
      linked inmunosorbent assay. Plasma cardiotrophin-1 progressively increased (P <
      0.001), along with progression of heart failure stages, in hypertensive patients.
      Plasma cardiotrophin-1 was directly (r = 0.416, P < 0.001) and inversely (r =
      0.263, P < 0.01) correlated with left ventricular (LV) mass index and ejection
      fraction, respectively, in all hypertensive patients. These associations were
      independent of a number of potential confounding factors. Receiver operating
      characteristic curves showed that a cut-off of 48.72 fmol/ml for cardiotrophin-1
      provided higher sensitivity for diagnosing stage C heart failure than a cut-off
      of 375.54 pg/ml for amino-terminal probrain natriuretic peptide (NT-proBNP) (80%
      vs. 72%). Sixty-four percent of stage C hypertensive patients with NT-proBNP
      values below 375.54 pg/ml value exhibited cardiotrophin-1 values above 49.16
      fmol/ml. These findings indicate that plasma cardiotrophin-1 is associated with
      progression of heart failure in hypertensive patients. Cardiotrophin-1
      measurement may provide additional information to that afforded by NT-proBNP to
      diagnose stage C heart failure in these patients.

PMID- 19155794
TI  - Plasma brain natriuretic peptide: a biochemical marker of effective blood
      pressure management?
AB  - OBJECTIVE: To investigate plasma brain natriuretic peptide (BNP) concentrations
      in association with blood pressure (BP) at baseline and after antihypertensive
      drug treatment. PATIENTS AND METHODS: We prospectively examined 186 individuals
      with newly diagnosed essential hypertension without target organ damage, whose
      mean age was 48.7 +/- 10.9 years. Treatment initiation began with irbesartan 150
      mg/day and was doubled at 4 weeks in cases of inadequate BP control. If
      indicated, at 8-week-follow-up hydrochlorothiazide 12.5 mg alone or with
      amlodipine 5-10 mg was added. BNP levels were measured at baseline and after 3
      months of antihypertensive treatment. RESULTS: At baseline plasma BNP levels were
      found to be related to systolic BP (r = 0.27, P < 0.001), independent of age,
      sex, smoking status, BMI and left ventricular mass index estimated by
      echocardiography (beta = 11.81, SE = 3.82, P = 0.002). Additionally, higher BNP
      concentrations were observed in patients with stage 2 hypertension compared with
      those with stage 1 (median 38.9 vs. 29.9 pg/ml, P = 0.022). Multivariate analysis
      showed a positive association between BNP and systolic BP variability (beta =
      0.03, SE = 0.01, P = 0.034). At follow-up, 64.7% of the participants who had
      achieved BP control showed decreased BNP levels in contrast to those with poor BP
      control (median change -14.5 vs. -1.3 and median range from -34.4 to -4.4 vs. 
      9.6 to 10.9, respectively, P < 0.001). CONCLUSION: In this hypertensive
      population, increased BNP concentrations are associated with higher BP levels and
      systolic BP variability. The fall of BNP observed in those who achieved BP
      control indicates that BNP could be used as a biochemical marker of effective BP
      control and target organ protection.

PMID- 19155797
TI  - Comments on the reproducibility of Ambulatory Arterial Stiffness Index and QKD.

PMID- 19155795
TI  - Doxazosin and heart failure: to be or not to be.

PMID- 19155799
TI  - Influencing the natural history of hypertension: is it the blood pressure
      achieved, the drug, or the drug dose?

PMID- 19155800
TI  - Iron and cardiovascular risk in menopause.

PMID- 19155803
TI  - The scientific contributions of Paul D. MacLean (1913-2007).
AB  - Paul D. MacLean, a leading brain scientist of the 20th century, died on December
      26, 2007. We review his life as a scientist and highlight some of his most
      important research contributions.

PMID- 19155804
TI  - Developing a risk-model of time to first-relapse for children and adolescents
      with a psychotic disorder.
AB  - Individuals treated for psychotic disorders and mood disorders with psychotic
      features have a high likelihood of relapse across the life course. This study
      examines the relapse rate and its associated predictors for children and
      adolescents experiencing a first-episode and develops a statistical risk-model
      for prediction of time to first-relapse. A multiyear, retrospective cohort design
      was used to track youth, under the age of 18 years, who experienced a first
      episode of psychosis, and were admitted to 1 of 6 inpatient hospital psychiatric
      units (N = 87). Participants were followed for at least 2 years (M = 3.9, SD =
      1.3) using survival analysis. Approximately 60% of subjects experienced relapse
      requiring hospital readmission by the end of follow-up, with 33% readmitted
      within the first year and 44% within 2 years. Median survival time was 34 months.
      Cox proportional hazards regression identified 4 key risk factors for relapse:
      medication nonadherence, female gender, receiving clinical treatment, and a
      decline in social support before first admission.

PMID- 19155805
TI  - Personality subtypes in disruptive adolescent males.
AB  - This study examined whether personality differences might account for meaningful
      heterogeneity within and across DSM-IV diagnostic categories for disruptive
      adolescent boys. In a broader study of personality pathology in adolescence, a
      national sample of 293 clinicians completed the Shedler-Westen Assessment
      Procedure 200-A on randomly selected outpatients aged 14 to 18 in their care. Of
      138 boys in the sample, 71 had a diagnosis of Disruptive Behavior Disorders or a
      history of arrests. Q-factor analysis identified 3 personality subtypes within
      this subsample: psychopathic (n = 28), social outcast (n = 22), and impulsive
      delinquent (n = 17). The subtypes differed on external criterion variables
      indicative of a valid taxonomic distinction, notably personality ratings,
      clinician-report child behavior checklist subscale scores, and etiologic
      variables. Personality subtypes converged with subtypes of delinquent boys
      identified by longitudinal research, and they showed substantial incremental
      validity in predicting adaptive functioning beyond Disruptive Behavior Disorders
      diagnoses. Results suggest that dimensional personality assessment in
      disruptive/delinquent adolescent boys provides information beyond existing
      diagnoses that may prove useful in prevention, clinical conceptualization, and
      treatment.

PMID- 19155806
TI  - Re-examining the long-term effects of experiencing parental death in childhood on
      adult psychopathology.
AB  - This study examined whether the experience of the death of a parent in childhood
      increases risk for adult psychopathology. Participants consisted of 3481 men and
      women gathered through the Baltimore Epidemiologic Catchment Area study in 1981
      and followed through 1994-1995. The Diagnostic Interview Survey was administered
      by trained interviewers and was used to assess DSM-III disorders including major
      depression, panic, and anxiety disorders. Maternal death was not a predictor of
      adult psychopathology. The death of the father during childhood more than doubled
      the risk for major depressive disorder in adulthood. This study did not find any
      significant interactions between gender of the deceased parent and gender of the
      participant nor did the current age of the participant or their age at the time
      of the death of a parent affect risk for adult psychopathology. The long-term
      effect on adult depression of the experience of the death of the father in
      childhood is attributed to likely financial stresses, which may have continued
      for years and possibly into early adulthood, complicating the family's adaptation
      to the initial loss.

PMID- 19155807
TI  - Improvement and recovery from suicidal and self-destructive phenomena in
      treatment-refractory disorders.
AB  - Long-term data about recovery from suicidal and self-destructive phenomena are
      limited. We examined these phenomena in a naturalistic, follow-along study of 226
      adults with treatment-refractory disorders admitted at the Austen Riggs Center.
      Follow-along interviews systematically rated suicidal ideation, suicide attempts,
      self-mutilation, and other self-destructive phenomena. We identified vital status
      in 98.7%, finding 1 death by suicide. Among 79 who made at least 1 suicide
      attempt in the 6 months before admission, 61 (77.2%) were estimated to be free of
      suicidal acts by a median of 7.18 years. Self-mutilation and other self
      destructive phenomena showed slightly longer times to recovery. Among 156
      individuals with suicidal ideation, 79 (50.6%) attained sustained recovery at a
      median of 8.69 years. On average 2.9 to 5.2 years were required from the last
      observed self-destructive event to attain sustained recovery. Most participants
      showed significant improvement in suicidal phenomena, whereas between 50.6% and
      77.2% attained sustained recoveries.

PMID- 19155808
TI  - Does cannabis use affect treatment outcome in bipolar disorder? A longitudinal
      analysis.
AB  - Research suggests that cannabis use affects negatively on onset and outcome of
      schizophrenia, but less is known about possible effects in mood disorders.
      Bipolar in- and outpatients (N = 3459) were enrolled in an observational study.
      The influence of cannabis exposure on clinical and social treatment outcome
      measures was examined over the course of 1 year, as well as the effects on these
      associations of third mediating variables. Over 12 months of treatment, cannabis
      users exhibited less compliance and higher levels of overall illness severity,
      mania, and psychosis compared with nonusers. Additionally, cannabis users
      experienced less satisfaction with life and had a lower probability of having a
      relationship compared with nonusers. There was little evidence that cannabis
      outcome associations were mediated by third variables. An independent impact of
      cannabis use on psychopathologic outcomes in patients with bipolar disorder was
      apparent, whereas the impact on social outcomes was modest.

PMID- 19155809
TI  - Empirical identification and validation of eating disorder phenotypes in a
      multisite clinical sample.
AB  - Identified problems with the classification system of eating disorders (EDs),
      including its imperfect application to clinical samples, challenge its validity
      and limit its utility. The present study aimed to empirically identify and
      validate ED phenotypes in a multisite clinical sample using latent profile
      analysis (LPA). ED symptom data collected from 687 individuals were included in
      LPA. Identified latent profiles (LPs) were compared on clinical validators. Five
      LPs were identified: LP1 (n = 178), objective bingeing and multiple purging
      methods; LP2 (n = 172), objective bingeing without purging; LP3 (n = 130),
      objective bingeing and vomiting; LP4 (n = 108), low/normal weight and excessive
      exercise; LP5 (n = 99), low/normal weight and absence of ED symptoms. Validation
      analyses demonstrated the most extreme psychopathology/medical morbidity in LP1
      and the least in LP5. LP1 and LP3 were most likely to report medication treatment
      for EDs. Identified LPs imperfectly resembled diagnostic and statistical manual
      of mental disorders-IV-TR EDs. Multiple purging methods and the absence of ED
      cognitions marked differences in severity across groups, whereas low weight did
      not. Clinical differences in psychopathology, medical morbidity, and treatment
      utilization validated groups. Future research should examine longitudinal
      stability of empirically-derived phenotypes and incremental validity of
      alternative classification schema to inform DSM-V.

PMID- 19155810
TI  - Validity of DSM-IV axis V global assessment of relational functioning scale: a
      multimethod assessment.
AB  - We investigate the convergent validity of the DSM-IV Axis V Global Assessment of
      Relational Functioning Scale (GARF; American Psychiatric Association, 1994). This
      study included 79 patients at a university-based outpatient treatment clinic. We
      examined clinician-rated GARF and the relationship to self-reported (Inventory of
      Interpersonal Problems; IIP-C; Horowitz et al. 2000) and free response themes
      [Social Cognition and Object Relations Scale: SCORS; Hilsenroth, Stein & Pinsker,
      2004; Westen, 1995] of interpersonal functioning. Clinician ratings of the GARF
      scale and SCORS variables were highly reliable and internally consistent.
      Convergent Validity among the GARF, SCORS, and IIP scores was calculated using a
      Principal Components Analysis and Confirmatory Factor Analysis (CFA). Results of
      the Principal Components Analysis revealed that the GARF, SCORS, and IIP scores
      converged on a single factor, although findings of the CFA did not fully confirm
      the 1 factor model originally proposed. Intercorrelations among the GARF, SCORS,
      and IIP variables were analyzed and a pattern of significant relationships was
      found between the GARF and SCORS variables. This study helps support the
      convergent validity GARF as a relational functioning measure and is one of the
      first investigations to examine this scale multidimensionally.

PMID- 19155811
TI  - Predictors of PTSD symptoms in response to psychosis and psychiatric admission.
AB  - The experiences of psychosis and psychiatric admission have the potential to act
      as events precipitating posttraumatic stress disorder (PTSD) symptoms. Known risk
      factors for the development of PTSD symptoms in adults were identified. These
      included childhood trauma, current psychiatric symptoms, perceived coercion, and
      relationships with mental health service providers. These factors were analyzed
      to determine if they were important in the development of PTSD symptoms in
      response to psychosis and admission. We used a cross-sectional design with a
      sample of 47 participants recruited from a service in Northern Ireland who had
      experienced psychosis and been discharged from inpatient treatment within 12
      months of data collection. The main outcome measure was the impact of events
      scale-revised. Data was subject to correlation analyses. A cut-off point of r =
      +/- 0.25 was used to select variables for inclusion in hierarchical regression
      analyses. Forty-five percent and 31% of the sample had moderate to severe PTSD
      symptoms related to psychosis and admission, respectively. The majority of
      participants identified positive symptoms and the first admission as the most
      distressing aspects of psychosis and admission. Childhood sexual and physical
      traumas were significant predictors of some PTSD symptoms. Strong association was
      found between current affective symptoms and PTSD symptoms. A reduced sense of
      availability of mental health service providers was also associated with PTSD
      symptoms and depression. Awareness of risk factors for the development of PTSD
      symptoms in response to admission and psychosis raises important issues for
      services and has implications for interventions provided.

PMID- 19155812
TI  - The associations between depression, health-related quality of life, social
      support, life satisfaction, and disability in community-dwelling US adults.
AB  - The purpose of this manuscript is to describe the associations among current
      depression, as measured by the Patient Health Questionnaire 8, health-related
      quality of life, social support, life satisfaction, and disability status, using
      the 2006 Behavioral Risk Factor Surveillance System. A dose-response relationship
      exists between depression severity and mean number of days in the past 30 days of
      physical distress, pain, anxiety symptoms, and activity limitations as well as
      the prevalence of fair/poor general health, life dissatisfaction, inadequate
      social support, and disability. These profound associations underscore the need
      for recognition and treatment of depression in all healthcare settings.

PMID- 19155813
TI  - Early adverse experiences in schizophrenia and unipolar depression.
AB  - To study the prevalence of early adversities in schizophrenia and unipolar
      depression, 2 groups of consecutive adult-onset inpatients with DSM-IV diagnoses
      of schizophrenia (n = 173) and unipolar depression (n = 305) were compared with
      an unscreened control group of volunteers from the general population (n = 310),
      with respect to their association with 4 types of childhood abuse and with early
      parental adversities (discord, separation, death, psychiatric caseness). Compared
      with general population, most types of early adversities (except sexual abuse and
      parental death) were significantly associated with both clinical groups. Compared
      with depression, all early adversities with the same 2 exceptions were
      significantly associated with schizophrenia; both frequency of abuse and number
      of types of abuse increased the risk of schizophrenia in a dose-response pattern,
      suggesting causality. These findings stress the role of social developmental
      factors in the etiology of schizophrenia.

PMID- 19155814
TI  - Toward understanding the usefulness of complementary and alternative medicine for
      individuals with serious mental illnesses: classification of perceived benefits.
AB  - Complementary and alternative medicine (CAM) has been gaining interest among
      individuals with serious mental illnesses. Yet, very little is known about how
      CAM may be beneficial to mental health. This study explored the specific benefits
      attributed to CAM by a national sample of 255 individuals with a serious mental
      illness who experienced CAM as having a positive impact on their mental health.
      Data about the CAM benefits were gathered through open-ended questions embedded
      in a mail survey that examined the patterns of CAM use in this population.
      Qualitative analysis revealed a wide spectrum of benefits that encompassed all
      major areas of human functioning, including physical, emotional, cognitive, self,
      social, spiritual, and overall functioning, and addressed both the improvement of
      psychiatric symptomatology and the promotion of functional recovery. Study
      findings provide useful information that can guide both everyday clinical
      practice and future research on the efficacy of CAM for psychiatric populations.

PMID- 19155815
TI  - Estimating the risk of violence from legally obtainable guns.

PMID- 19155819
TI  - Context for WOC practice: assessment, prevention, and intervention in wound,
      ostomy and continence care.

PMID- 19155820
TI  - Data collection methods series. Part 1: Define a clear purpose for collecting
      data.

PMID- 19155821
TI  - Nursing interventions to reduce the risk of catheter-associated urinary tract
      infection. Part 1: Catheter selection.
AB  - BACKGROUND: The urinary system is the most common site for all hospital-acquired
      infections, accounting for approximately 40% of all nosocomial infections. The US
      Centers for Medicare & Medicaid Services has enacted 2 policies that have focused
      considerable attention on the optimal use of indwelling catheters in the acute
      and long-term care settings and the prevention of complications including
      catheter-associated urinary tract infection (CAUTI). OBJECTIVES: This is the
      first of a 2-part Evidence-Based Report Card reviewing current evidence
      pertaining to nursing actions for prevention of CAUTIs in patients with short-
      and long-term indwelling catheters. Part 1 reviews evidence for materials for
      catheter construction, including incorporation of antimicrobial substances into
      the catheter, and selection of catheter size. SEARCH STRATEGY: Nursing actions
      for prevention of CAUTIs were identified based on search of electronic databases
      and Web-based search engines for national or international clinical practice
      guidelines focusing on this topic. Evidence related to 2 common nursing
      interventions, selection of the material of construction and selection of
      catheter size, was identified by searching electronic databases MEDLINE, CINAHL,
      the Cochrane Library, and the ancestry of articles identified in these searches.
      RESULTS: We found robust evidence supporting insertion of a silver alloy-coated
      catheter to reduce the risk of CAUTIs for up to 2 weeks in adult patients managed
      by short-term indwelling catheterization. We also found evidence supporting the
      insertion of an antibiotic-impregnated catheter for reduction of CAUTI risk for
      up to 7 days. There was insufficient evidence to determine whether regular use of
      an antimicrobial catheter reduces the risk of CAUTIs in adults managed with long
      term indwelling catheterization. There was insufficient evidence to determine
      whether selection of a latex catheter, hydrogel-coated latex catheter, silicone
      coated latex catheter, or all- silicone catheter influences CAUTI risk. Expert
      opinion suggests that selection of a smaller French-sized catheter reduces CAUTI
      risk, but evidence is lacking. IMPLICATIONS FOR PRACTICE: Insertion of an
      antimicrobial catheter, either silver alloy or antimicrobial coated, is
      recommended for patients with short-term indwelling catheterization. There is
      insufficient evidence to recommend their use in patients managed by long-term
      indwelling catheterization. Selection of smaller French sizes for short- or long
      term catheterization is thought to improve comfort and reduce CAUTI risk, but
      further research is needed to substantiate these best practice recommendations.

PMID- 19155822
TI  - What's new in lower-extremity arterial disease? WOCN's 2008 clinical practice
      guideline.
AB  - Lower-extremity arterial disease (LEAD) affects 8 to 10 million people in the
      United States, resulting in pain, tissue loss, infection, limb loss, and an
      impaired quality of life. LEAD is underdiagnosed, undertreated, and often
      unrecognized. The purpose of this article is to provide a summary of the
      recommendations from the 2008 evidence-based, clinical practice guideline,
      Guideline for the Management of Patients With Lower-Extremity Arterial Disease,
      recently released from the Wound, Ostomy and Continence Nurses Society. This
      article presents an overview of the process used to develop the guideline, a
      discussion of risks for LEAD, and specific recommendations for assessment,
      interventions, patient education, and risk-reduction strategies.

PMID- 19155823
TI  - Reducing hospital-acquired pressure ulcers.
AB  - The cost of treating a hospital-acquired pressure ulcer (HAPU) places a
      significant burden on healthcare facilities. Associated expenses potentially
      include increased supplies, equipment, specialty beds, staffing, nutritional
      support, laboratory testing, and hospital length of stay. The quarterly HAPU data
      revealed an increased prevalence in our 25-bed intermediate care unit at Central
      DuPage Hospital at Winfield, Illinois. There were 6 occurrences of HAPU during
      fiscal year 2005 to fiscal year 2006, and 5 occurred during fiscal year 2006 to
      2007. Based on these data, our unit quality council investigated contributory
      factors and reviewed current tools and standards of practice related to pressure
      ulcer prevention. Strategic plans were developed to reduce the incidence of HAPU.
      Follow-up monitoring revealed no HAPU occurrence from October 2006 through
      September 2007. Pressure ulcer prevention strategies proved effective in reducing
      incidence during a 1-year period and have been approved as standards of practice
      for the unit.

PMID- 19155824
TI  - Honey-based dressings and wound care: an option for care in the United States.
AB  - Honey-based wound dressings have been used worldwide since ancient times. A honey
      product received US Federal Drug Administration approval in 2007, making this
      dressing an option for wound care. Honey has been found to exert anti
      inflammatory and antibacterial effects without antibiotic resistance, promote
      moist wound healing, and facilitate debridement. However, it may cause a stinging
      pain. As is true of any wound dressing, its use must be carefully selected and
      monitored. Continued research is needed to add to its evidence base. This article
      provides a summary of the current evidence base for the use of honey and a review
      of its therapeutic effects and discusses implications for WOC nursing practice.

PMID- 19155826
TI  - View from here: functional urinary incontinence ICD-9.

PMID- 19155827
TI  - Do catheter washouts extend patency time in long-term indwelling urethral
      catheters? A randomized controlled trial of acidic washout solution, normal
      saline washout, or standard care.
AB  - PURPOSE: Blockage of long-term indwelling catheters with mineral deposit is an
      ongoing management issue, but evidence on optimal management is lacking. Our
      purpose was to examine whether catheter washouts prevent or reduce catheter
      blockage. DESIGN: A multisite randomized controlled trial. SUBJECTS AND SETTING:
      Adults with long-term indwelling catheters that required changing every 3 weeks
      or less, living in the community, and requiring supportive or continuing care
      were recruited. Participants were randomly assigned to 1 of 3 groups: control
      (usual care, no washout), saline washout, or commercially available acidic
      washout solution (Contisol Maelor Pharmaceuticals Ltd, Wrexham, UK). METHODS: At
      baseline visit, the catheter was changed and participants were followed weekly
      for 8 weeks, with checks for catheter patency and urine pH. Participants
      randomized to saline or commercial solution had a weekly washout with the
      appropriate solution. Endpoints were 8 weeks (completion data), 3 or more
      catheter changes in the 8-week period, or symptomatic urinary tract infection
      (UTI) requiring antibiotics. The study hypothesis was that catheter life would be
      extended by 25% in the commercial solution group. It was not possible to blind
      participants or research nurses to washout versus no intervention, but
      participants in the saline and washout solution groups were blinded to solution
      type. RESULTS: One hundred twelve potential participants were screened; 73 were
      enrolled, randomized, and included in the final analysis. Of these, 53 completed
      the full 8 weeks of data collection; 16 terminated early because of 3 catheter
      changes or self-reported 'UTI'. Other reasons for termination were hematuria,
      latex sensitivity, deceased/severe illness, or personal choice. Analysis of
      variance was used to analyze mean differences on demographic variables and mean
      number of weeks in study. Kaplan-Meier survival curve analysis showed no
      statistical difference between the groups in time to first catheter change.
      CONCLUSION: At this time, the evidence is insufficient to state whether catheter
      washout with saline or Contisol is more effective than usual care with no washout
      in preventing blocking. No increased risk of UTI was associated with washout
      regimes.

PMID- 19155828
TI  - Pressure ulcers.

PMID- 19155829
TI  - Managing the cutaneous vesicostomy.

PMID- 19155831
TI  - Tightening the belt in 2009.

PMID- 19155832
TI  - Taking a stand.

PMID- 19155833
TI  - Huddle up!

PMID- 19155834
TI  - Beyond orientation: Developing and retaining new graduate nurses.

PMID- 19155835
TI  - Foster EBP with CARF accreditation.

PMID- 19155836
TI  - Frustrated with HIT? Get involved!

PMID- 19155837
TI  - Influenza season: are you ready?

PMID- 19155839
TI  - Visionary Leader 2008.

PMID- 19155840
TI  - Dress code debate.

PMID- 19155841
TI  - The virtual ICU: pathway to improved performance.

PMID- 19155842
TI  - ADEs and automation.

PMID- 19155843
TI  - Portable ultrasound: A cost-effective process improvement tool for PICC
      placement.

PMID- 19155844
TI  - ED overcrowding: Implications for nurse leaders.

PMID- 19155846
TI  - A little humility goes a long way.

PMID- 19155845
TI  - Facing burnout, aging staff.

PMID- 19155847
TI  - Developing a shared-governance strategy to address floating.

PMID- 19155848
TI  - Is your facility's Web site recruitment friendly?

PMID- 19155849
TI  - Circle of excellence. Does regular rounding by nursing associates boost patient
      satisfaction?

PMID- 19155850
TI  - Decrease recovery time with proper pain management.

PMID- 19155852
TI  - Nursing and realities of clinical research.

PMID- 19155853
TI  - Succession planning: after you, then who?

PMID- 19155854
TI  - Caring for morbidly obese patients: safety considerations for nurse
      administrators.

PMID- 19155855
TI  - Flexible adaptation: managing beyond your scope.

PMID- 19155856
TI  - Establishing a dress code, BSN differential.

PMID- 19155857
TI  - No need to hit the panic button.

PMID- 19155858
TI  - Where have all the new grads gone?

PMID- 19155859
TI  - Better patient surveillance.

PMID- 19155860
TI  - Virtual ICUs, lower operational costs.

PMID- 19155861
TI  - Evidence-based design.

PMID- 19155862
TI  - Open shift management.

PMID- 19155863
TI  - Empowerment through automated labor resource management.

PMID- 19155865
TI  - Healthcare in the home.

PMID- 19155864
TI  - Targeting "never events".

PMID- 19155867
TI  - Engaging organizational support for the Magnet journey.

PMID- 19155869
TI  - Tackling open visitation, 1:1 coverage.

PMID- 19155870
TI  - Do your patients know about third-hand smoke?

PMID- 19155871
TI  - Risk management: an overview of general concepts.

PMID- 19155872
TI  - Advocate change one nurse at a time.

PMID- 19155873
TI  - A nonpharmacologic adjunct for pain management.

PMID- 19155874
TI  - On the road to better dyslipidemia outcomes.

PMID- 19155876
TI  - Guide to Care for patients. Lowering your cholesterol.

PMID- 19155877
TI  - Drug approvals: '08 in review. Nebivolol (Bystolic).

PMID- 19155878
TI  - Drug approvals: '08 in review. Certolizumab pegol (Cimzia).

PMID- 19155879
TI  - Drug approvals: '08 in review. Desvenlafaxine (Pristiq).

PMID- 19155880
TI  - Drug approvals: '08 in review. Olopatadine hydrochloride (Patanase) nasal spray.

PMID- 19155881
TI  - Drug approvals: '08 in review. Rotavirus vaccine, live, oral (Rotarix).

PMID- 19155882
TI  - Drug approvals: '08 in review. Methylnaltrexone (Relistor).

PMID- 19155883
TI  - Drug approvals: '08 in review. Ciclesonide (Alvesco).

PMID- 19155885
TI  - Actinic keratosis: do the numbers add up?

PMID- 19155886
TI  - Neuropsychiatric concerns related to influenza treatment.

PMID- 19155887
TI  - Vulvar cancer in the wake of increasing incidence.

PMID- 19155891
TI  - Keeping current on women's health care.

PMID- 19155892
TI  - Pelvic pain phenotyping: the key to progress.

PMID- 19155893
TI  - Measurement of acute pelvic pain intensity in gynecology: a comparison of five
      methods.
AB  - OBJECTIVE: To compare different methods for measuring pelvic pain intensity in a
      gynecologic emergency unit. METHODS: A total of 177 consecutive female patients,
      with or without pain, consulting in a gynecologic emergency unit, underwent
      initial pain evaluation. We used three self-report pain intensity scales: visual
      analog scale, numeric rating scale, and verbal rating scale, and two nonverbal
      structured behavioral indices (BI-1, first behavioral index, BI-2 second
      behavioral index). Diagnosis and treatment took place in routine manner. RESULTS:
      The five scales were unidimensional according to principal component analysis
      (Cronbach's alpha coefficient=0.89). Missing data rates were greater for the two
      behavioral scales than for the self-report scales (n=177; 6.2% for BI-1 and 12.4%
      for BI-2). Patients had lower scores with the behavioral scales than with the
      self-report ones. Variations of pain intensity according to the pain physiology
      or the pain location were similar whatever the method of measurement used. The
      five methods were all sensitive to the physiology of the pain, the location and
      the severity of the illness, and pain as a main complaint. None of the methods
      used was affected by age, occupational categories, parity, or geographical
      origins. CONCLUSION: All methods adequately measured the pelvic pain intensity in
      gynecologic emergencies. The self-report scales were easier to use than the
      behavioral indices. Self-report measurements of pelvic pain intensity provide
      useful information at the time of triage in gynecologic emergency departments.
      LEVEL OF EVIDENCE: II.

PMID- 19155894
TI  - Failure and regret after laparoscopic filshie clip sterilization under local
      anesthetic.
AB  - OBJECTIVE: To estimate the failure, regret, and reversal rates 5 or more years
      after laparoscopic Filshie clip sterilization using local anesthesia. METHODS: A
      total of 1,101 women underwent Filshie clip sterilization between 1983 and 2002.
      They completed follow-up questionnaires that were analyzed for the following
      outcomes: failed sterilization, regret after the operation, and sterilization
      reversal. RESULTS: Two hundred thirty-three of 968 (24%) eligible women sent the
      questionnaire had moved from their last known address. Of the remaining 735
      women, 573 (78%) completed the questionnaire: 223 (39%) 5-6 years after the
      operation, 175 (30%) after 7-9 years, and 175 (30%) after 10-15 years. One
      pregnancy occurred 10 months after surgery, and one woman had the procedure
      repeated when unilateral tubal patency was identified by hysterosalpingography 3
      weeks after surgery. Twenty-four (4%) women regretted having the operation; 7
      (1.2%) women had a reversal operation, and all subsequently conceived.
      CONCLUSION: Failure after tubal sterilization using Filshie clips is less than
      1:500 operations. Patient selection and surgeons' experience may have influenced
      these results. Regret occurred in a small proportion. LEVEL OF EVIDENCE: III.

PMID- 19155895
TI  - Oral compared with intravenous sedation for first-trimester surgical abortion: a
      randomized controlled trial.
AB  - OBJECTIVE: To test the equivalency of oral sedation and intravenous sedation for
      pain control in first-trimester surgical abortion. METHODS: Women undergoing
      suction curettage at less than 13 weeks of gestation were randomly assigned to
      oral sedation, 10 mg of oxycodone and 1 mg of lorazepam, or intravenous sedation,
      100 micrograms fentanyl and 2 mg midazolam. All patients received 800 mg of
      preoperative ibuprofen and a 20-mL paracervical block with 1% lidocaine. The
      primary outcome was intraoperative pain as measured on a 21-point verbal rating
      scale that had a range from 0 to 100 (0=no pain and 100=worst pain ever) with an
      equivalence margin for the treatment group comparison of +/-10. RESULTS: Of 130
      women, 65 were randomly assigned to oral sedation and 65 to intravenous sedation.
      The groups differed at baseline by age and preoperative ratings of depression,
      stress, and anxiety; however, when adjusted for these differences, the primary
      results were unaffected. Mean intraoperative pain scores, controlling for age and
      preoperative depression, stress, and anxiety, were 61.2 for oral sedation and
      36.3 for intravenous sedation (mean difference 24.9, 95% confidence interval 15.9
      33.9). Other findings included no difference in postoperative adverse effects and
      less satisfaction with pain control with oral sedation compared with intravenous
      sedation. CONCLUSION: Oral sedation, as studied, is not equivalent to intravenous
      sedation for pain control during first-trimester surgical abortion. CLINICAL
      TRIAL REGISTRATION: : ClinicalTrials.gov, www.clinicaltrials.gov, NCT00337792
      LEVEL OF EVIDENCE: I.

PMID- 19155896
TI  - Prevention of preterm birth in triplets using 17 alpha-hydroxyprogesterone
      caproate: a randomized controlled trial.
AB  - OBJECTIVE: To assess whether 17 alpha-hydroxyprogesterone caproate reduces the
      rate of preterm birth in women carrying triplets. METHODS: We performed this
      randomized, double-blinded, placebo-controlled trial in 14 centers. Healthy women
      with triplets were randomly assigned to weekly intramuscular injections of either
      250 mg of 17 alpha-hydroxyprogesterone caproate or matching placebo, starting at
      16-20 weeks and ending at delivery or 35 weeks of gestation. The primary study
      outcome was delivery or fetal loss before 35 weeks. RESULTS: One hundred thirty
      four women were assigned, 71 to 17 alpha-hydroxyprogesterone caproate and 63 to
      placebo; none were lost to follow-up. Baseline demographic data were similar in
      the two groups. The proportion of women experiencing the primary outcome (a
      composite of delivery or fetal loss before 35 0/7 weeks) was similar in the two
      treatment groups: 83% of pregnancies in the 17 alpha-hydroxyprogesterone caproate
      group and 84% in the placebo group, relative risk 1.0, 95% confidence interval
      0.9-1.1. The lack of benefit of 17 alpha-hydroxyprogesterone caproate was evident
      regardless of the conception method or whether a gestational age cutoff for
      delivery was set at 32 or 28 weeks. CONCLUSION: Treatment with 17 alpha
      hydroxyprogesterone caproate did not reduce the rate of preterm birth in women
      with triplet gestations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      www.clinicaltrials.gov, NCT00099164 LEVEL OF EVIDENCE: I.

PMID- 19155897
TI  - Severe obstetric morbidity in the United States: 1998-2005.
AB  - OBJECTIVE: To examine trends in the rates of severe obstetric complications and
      the potential contribution of changes in delivery mode and maternal
      characteristics to these trends. METHODS: We performed a cross-sectional study of
      severe obstetric complications identified from the 1998-2005 Nationwide Inpatient
      Sample of the Healthcare Cost and Utilization Project. Logistic regression was
      used to examine the effect of changes in delivery mode and maternal
      characteristics on rates of severe obstetric complications. RESULTS: The
      prevalence of delivery hospitalizations (per 1,000) complicated by at least one
      severe obstetric complication increased from 0.64% (n=48,645) in 1998-1999 to
      0.81% (n=68,433) in 2004-2005. Rates of complications that increased
      significantly during the study period included renal failure by 21% (from 0.23 to
      0.28), pulmonary embolism by 52% (0.12 to 0.18), adult respiratory distress
      syndrome by 26% (0.36 to 0.45), shock by 24% (0.15 to 0.19), blood transfusion by
      92% (2.38 to 4.58), and ventilation by 21 % (0.47 to 0.57). In logistic
      regression models, adjustment for maternal age had no effect on the increased
      risk for these complications in 2004-2005 relative to 1998-1999. However, after
      adjustment for mode of delivery, the increased risks for these complications in
      2004-2005 relative to 1998-1999 were no longer significant, with the exception of
      pulmonary embolism (odds ratio 1.30) and blood transfusion (odds ratio 1.72).
      Further adjustment for payer, multiple births, and select comorbidities had
      little effect. CONCLUSION: Rates of severe obstetric complications increased from
      1998-1999 to 2004-2005. For many of these complications, these increases were
      associated with the increasing rate of cesarean delivery. LEVEL OF EVIDENCE: III.

PMID- 19155898
TI  - The effect of teenage maternal obesity on perinatal outcomes.
AB  - OBJECTIVE: To estimate the effect of obesity on perinatal outcomes among inner
      city teenage pregnant women. METHODS: In this retrospective cohort study, we
      reviewed all nulliparous teenaged (aged 18 years and younger) deliveries at the
      Washington Hospital Center between 2000 and 2004. Overweight and obese teenagers
      (body mass index at or above 25.0 kg/m) were compared with normal-weight (body
      mass index less than 25.0 kg/m) teenagers. Frequencies and odds ratios for
      adverse maternal-fetal outcomes were calculated. RESULTS: Of the 10,322
      deliveries that occurred during the study period, 712 (7%) were to teenagers.
      Among the 458 nulliparous teenaged mothers, 274 (60%) were normal weight and 184
      (40%) were overweight/obese. Compared with normal-weight teens (n=274), obese
      teens (n=78) were at higher risk for cesarean delivery (adjusted odds ration [OR]
      4.3, 95% confidence interval [CI] 2.4-7.6) and gestational diabetes (adjusted OR
      4.2, 95% CI 1.5-12.1). Overweight teens (n=106) had lower risk for preterm birth
      at less than 37 and less than 34 weeks of gestation (adjusted OR 0.28, 95% CI
      0.10-0.77 and adjusted OR 0.11, 95% CI 0.01-0.80, respectively). CONCLUSION:
      Overweight and obese teenage mothers are at increased risk for adverse perinatal
      outcomes. Research on optimal weight for pregnant teens and weight control
      interventions is needed. LEVEL OF EVIDENCE: II.

PMID- 19155899
TI  - Preventing excessive weight gain during pregnancy through dietary and lifestyle
      counseling: a randomized controlled trial.
AB  - OBJECTIVE: To estimate whether an organized, consistent program of dietary and
      lifestyle counseling prevents excessive weight gain in pregnancy. METHODS: This
      randomized controlled trial assigned women to receive either an organized,
      consistent program of intensive dietary and lifestyle counseling or routine
      prenatal care. The primary study outcome was the proportion of patients whose
      gestational weight gain was within the Institute of Medicine (IOM) guidelines.
      Secondary outcomes included mode of delivery, rate of operative vaginal delivery,
      neonatal weight, and the incidence of preeclampsia, gestational diabetes mellitus
      (GDM), vaginal/perineal lacerations, and shoulder dystocia. RESULTS: A total of
      100 women were randomized to the study (lifestyle counseling 57, routine prenatal
      care 43). Baseline demographic characteristics were similar between the study
      groups. The lifestyle counseling group gained significantly less weight than did
      the routine prenatal care group (28.7+/-12.5 lb compared with 35.6+/-15.5 lb,
      P=.01). The routine prenatal care group had significantly more cesarean
      deliveries due to "failure to progress" (routine prenatal care 58.3% compared
      with lifestyle counseling 25.0%, P=.02). Across groups, patients who were not
      adherent to the IOM guidelines had significantly heavier neonates (adherent
      3,203.2+/-427.2 g compared with not adherent 3,517.4+/-572.4 g, P<.01).
      Nulliparous women gained significantly more weight than did parous women (36.5+/
      14.5 lb compared with 27.7+/-12.7 lb, P<.01). The most predictive factor of IOM
      adherence was having a normal prepregnancy body mass index. No statistically
      significant differences were noted between the groups in adherence to IOM
      guidelines, rate of cesarean delivery, preeclampsia, GDM, operative vaginal
      delivery, or vaginal lacerations. CONCLUSION: An organized, consistent program of
      dietary and lifestyle counseling did reduce weight gain in pregnancy. CLINICAL
      TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00792480 LEVEL
      OF EVIDENCE: I.

PMID- 19155900
TI  - Cervical vasopressin compared with no premedication and blood loss during vaginal
      hysterectomy: a randomized controlled trial.
AB  - OBJECTIVE: To compare blood loss, operative time, postoperative pain medication
      requirements, and complication rates in patients undergoing vaginal hysterectomy
      who were randomly assigned to receive preoperative intracervical vasopressin or
      no intracervical injection. METHODS: Fifty-eight women undergoing vaginal
      hysterectomy were randomly allocated to receive either eight units of vasopressin
      intracervically or nothing preoperative from January 2004 to January 2005. A
      researcher blinded to the study group determined blood loss. The surgeries were
      performed using uniform steps by senior residents under the direction of two
      attending surgeons. Multiple preoperative and postoperative values were
      evaluated, including time to specific points in surgery and use of postoperative
      pain medication. Independent sample t tests, Fisher exact test, and Pearson chi
      tests were used to analyze the data. RESULTS: The two groups were similar in
      terms of age, weight, parity, and ethnicity. There was also no difference in
      indication for surgery or estimated uterine size. The vasopressin group lost
      significantly less blood (145.3 mL compared with 266.4 mL control; P=.022). There
      was a significant difference in the increase in mean blood pressure at 5 minutes
      after injection (10.4 for the vasopressin group compared with. 2.5 for the
      control group, P=.043). There was no significant difference in immediate recovery
      room morphine requirements, but patient-controlled anesthesia usage was
      significantly higher in the vasopressin group. CONCLUSION: The preoperative
      injection of intracervical vasopressin leads to decreased blood loss during
      vaginal hysterectomy. There was, however, a significant increase in postoperative
      morphine use in patients receiving vasopressin. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, www.clinicaltrials.gov, NCT00799292 LEVEL OF EVIDENCE: I.

PMID- 19155901
TI  - Radiation-associated endometrial cancer.
AB  - OBJECTIVE: To compare prognostic variables and survival of radiation-associated
      endometrial cancers with sporadic second endometrial cancers. METHODS: Patients
      with primary cancers of pelvic organs (urinary system, colorectal, cervix, vulva,
      and vagina) were identified from the Surveillance, Epidemiology, and End Results
      (SEER) database between 1973 and 2005. Among these patients, those who received
      pelvic radiation and subsequently developed endometrial cancer formed the
      radiation-associated endometrial cancers cohort (cases), whereas those who did
      not receive pelvic radiation but subsequently developed endometrial cancer formed
      the sporadic second endometrial cancers cohort (controls). Comparisons between
      radiation-associated endometrial cancers and sporadic second endometrial cancers
      used chi, t tests, Kaplan-Meier, and cox proportional hazards analysis. RESULTS:
      In 205 radiation-associated endometrial cancer patients and 1,001 sporadic second
      endometrial cancer patients, the mean age of diagnosis was 65 years and 68 years,
      respectively (P<.001). The mean latency between primary pelvic organ cancer and
      second endometrial cancer was 110 months for the radiation-associated endometrial
      cancers and 77 months for the sporadic second endometrial cancers (P=.03). The
      lesions in the radiation-associated endometrial cancers cohort (compared with
      sporadic second endometrial cancers) were far more likely to be nonendometrioid
      histology (76.2% compared with 51%, P<.001), poorly differentiated (58% compared
      with 28%, P<.001), and advanced stage (International Federation of Gynecology and
      Obstetrics III and IV [corrected] combined) (43% compared with 16%, P<.001). The
      5-year survival rate for radiation-associated endometrial cancers and sporadic
      second endometrial cancers was 27.1% and 57.1%, respectively (P<.001). In
      multivariable analysis, after controlling for age, race, histology, stage, grade,
      and treatment, the hazard ratio for death of radiation-associated [corrected]
      endometrial cancers was 1.4 (95% ((CI)) [corrected] 1.2-3.6; P=.002). CONCLUSION:
      The radiation-associated endometrial cancers carry a grave prognosis because they
      are more likely to be nonendometrioid, poorly differentiated advanced stage
      cancers. The longer latency and extensive spread at diagnosis among radiation
      associated endometrial cancers may suggest a possible delay in clinical
      presentation and diagnosis. LEVEL OF EVIDENCE: II.

PMID- 19155902
TI  - Earlier diagnosis and serum human chorionic gonadotropin regression in complete
      hydatidiform moles.
AB  - OBJECTIVE: To estimate serum human chorionic gonadotropin (hCG) regression in
      uneventful complete hydatidiform moles before and after the introduction of
      routine first-trimester ultrasonography. METHODS: Gestational age, maternal age,
      preevacuation hCG concentrations, serum hCG regression, and hCG disappearance
      time among a recent group of 137 women with uneventful complete hydatidiform
      moles that were found between 1994 and 2006 were evaluated retrospectively and
      compared with a historical cohort of 106 patients with complete moles that were
      found between 1977 and 1989. RESULTS: Gestational age, preevacuation hCG
      concentration, and hCG disappearance time were significantly lower in the recent
      complete hydatidiform mole cohort compared with the historic series. Ninety-nine
      percent of the recent cohort achieved hCG normalization within 19 weeks after
      uterine evacuation compared with 25 weeks in the historic group. CONCLUSION:
      Earlier serum hCG regression in the recent cohort of complete hydatidiform moles
      probably is a result of widely used first-trimester ultrasonography leading to
      detection and evacuation of complete moles at younger gestational ages, resulting
      in lower hCG levels at time of evacuation. LEVEL OF EVIDENCE: : II.

PMID- 19155903
TI  - Patterns of change in uterine artery Doppler studies between 20 and 24 weeks of
      gestation and pregnancy outcomes.
AB  - OBJECTIVES: To describe changes in mean uterine artery resistance index and
      bilateral notches between 20 and 24 weeks of gestation in healthy nulliparous
      women and to relate these changes to pregnancy outcome. METHODS: A total of 2,189
      nulliparous participants in the Screening for Pregnancy Endpoints study had
      pregnancy outcomes compared between four uterine artery Doppler groups: normal at
      20 and 24 weeks of gestation (group 1), normal at 20 weeks and abnormal at 24
      weeks (group 2), abnormal at 20 weeks and normal at 24 weeks (group 3), and
      abnormal at both 20 and 24 weeks (group 4). Abnormal uterine Doppler was defined
      as 1) mean resistance index greater than the 90th centile; 2) bilateral notches;
      and 3) a combination of 1, 2, or both. The main outcomes were preeclampsia and
      small for gestational age (SGA) neonates (less than the 10th customized centile).
      RESULTS: Preeclampsia developed in 116 (5.3%) women, and 223 (10.2%) delivered
      SGA neonates. With abnormal Doppler defined as mean resistance index greater than
      the 90th centile, the rate of SGA increased across Doppler groups: group 1, 156
      (8.4%); group 2, 13 (11%); group 3, 25 (19.5%); and group 4, 29 (35.4%) (P<.001).
      The rate of SGA was higher in group 3 compared with group 1. Preeclampsia
      differed among groups 1 (85 [4.6%]), 2 (9 [7.6%], 3 (7 [5.5%]), and 4 (15
      [18.3%]) (P<.001). CONCLUSION: Pregnancy outcomes in women with abnormal uterine
      artery Doppler results at either 20 or 24 weeks were intermediate between those
      with normal or abnormal results at both time points. If overall test performance
      could be enhanced by the addition of clinical data, biomarkers, or both, we would
      recommend that 20 weeks is the most appropriate gestation in the second trimester
      to perform uterine artery Doppler studies. LEVEL OF EVIDENCE: II.

PMID- 19155904
TI  - One-day compared with 7-day nitrofurantoin for asymptomatic bacteriuria in
      pregnancy: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate whether a 1-day nitrofurantoin regimen is as effective as
      a 7-day regimen in eradicating asymptomatic bacteriuria during pregnancy.
      METHODS: A multicenter, double-blind, randomized, placebo controlled
      noninferiority trial was conducted in antenatal clinics in Thailand, the
      Philippines, Vietnam, and Argentina. Pregnant women seeking antenatal care
      between March 2004 and March 2007 who met the inclusion and exclusion criteria
      were invited to participate in the study. Those who consented were randomly
      allocated to receive either a 1-day or a 7-day course of 100 mg capsules of
      nitrofurantoin, which was taken twice daily. The primary outcome was
      bacteriologic cure on day 14 of treatment. RESULTS: : A total of 1,248 of 24,430
      eligible women had asymptomatic bacteriuria, making the overall prevalence of
      5.1%. Of these 1,248 women, 778 women were successfully recruited, and 386 and
      392 women were randomly allocated to 1-day and 7-day regimens, respectively.
      Escherichia coli was the most common potentially pathogenic bacteria detected,
      its prevalence approaching 50%. Bacteriologic cure rates at treatment day 14 were
      75.7% and 86.2% for 1-day and 7-day regimens, respectively. The cure rate
      difference was -10.5% (95% confidence interval -16.1% to -4.9%). Mean birth
      weight and mean gestational age at delivery were significantly lower in the 1-day
      regimen group. There were fewer adverse effects in the 1-day regimen group, but
      the differences were not statistically significant. CONCLUSION: A 1-day regimen
      of nitrofurantoin is significantly less effective than a 7-day regimen. Women
      with asymptomatic bacteriuria in pregnancy should receive the standard 7-day
      regimen. CLINICAL TRIAL REGISTRATION: ISRCTN, isrctn.org, ISRCTN11966080 LEVEL OF
      EVIDENCE: I.

PMID- 19155905
TI  - Accuracy of diagnostic tests to detect asymptomatic bacteriuria during pregnancy.
AB  - OBJECTIVE: A dipslide is a plastic paddle coated with agar that is attached to a
      plastic cap that screws onto a sterile plastic vial. Our objective was to
      estimate the diagnostic accuracy of the dipslide culture technique to detect
      asymptomatic bacteriuria during pregnancy and to evaluate the accuracy of nitrate
      and leucocyte esterase dipslides for screening. METHODS: This was an ancillary
      study within a trial comparing single-day with 7-day therapy in treating
      asymptomatic bacteriuria. Clean-catch midstream samples were collected from
      pregnant women seeking routine care. Positive and negative likelihood ratios and
      sensitivity and specificity for the culture-based dipslide to detect and chemical
      dipsticks (nitrites, leukocyte esterase, or both) to screen were estimated using
      traditional urine culture as the "gold standard." RESULTS: : A total of 3,048
      eligible pregnant women were screened. The prevalence of asymptomatic bacteriuria
      was 15%, with Escherichia coli the most prevalent organism. The likelihood ratio
      for detecting asymptomatic bacteriuria with a positive dipslide test was 225 (95%
      confidence interval [CI] 113-449), increasing the probability of asymptomatic
      bacteriuria to 98%; the likelihood ratio for a negative dipslide test was 0.02
      (95% CI 0.01-0.05), reducing the probability of bacteriuria to less than 1%. The
      positive likelihood ratio of leukocyte esterase and nitrite dipsticks (when both
      or either one was positive) was 6.95 (95% CI 5.80-8.33), increasing the
      probability of bacteriuria to only 54%; the negative likelihood ratio was 0.50
      (95% CI 0.45-0.57), reducing the probability to 8%. CONCLUSION: A pregnant woman
      with a positive dipslide test is very likely to have a definitive diagnosis of
      asymptomatic bacteriuria, whereas a negative result effectively rules out the
      presence of bacteriuria. Dipsticks that measure nitrites and leukocyte esterase
      have low sensitivity for use in screening for asymptomatic bacteriuria during
      gestation. CLINICAL TRIAL REGISTRATION: ISRCTN, isrctn.org, 1196608 LEVEL OF
      EVIDENCE: II.

PMID- 19155906
TI  - Perinatal outcome of monoamniotic twin pregnancies.
AB  - OBJECTIVE: To study perinatal mortality and neonatal morbidity in a large cohort
      of monoamniotic twin pregnancies with special emphasis to the gestational age
      specific mortality. METHODS: The study included monoamniotic twin pregnancies
      delivered in 10 perinatal centers in the Netherlands between January 2000 and
      December 2007. RESULTS: A total of 98 monoamniotic pregnancies were included. The
      perinatal mortality rate (20 weeks of gestation through 28 days of life) was 19%;
      after exclusion of fetuses with lethal anomalies, the rate was 17%. After 32
      weeks of gestation, only two pregnancies were complicated by perinatal mortality
      (4%). The incidence of twin-twin transfusion syndrome was 6%. The incidence of
      congenital heart anomalies and cerebral injury was 4% and 5%, respectively.
      CONCLUSION: The current incidence of perinatal mortality in monoamniotic twins is
      considerably lower than in previous decades, but it is still high and occurs
      throughout pregnancy. LEVEL OF EVIDENCE: III.

PMID- 19155907
TI  - Risk factors for neurodevelopment impairment in twin-twin transfusion syndrome
      treated with fetoscopic laser surgery.
AB  - OBJECTIVE: To estimate the risk factors for adverse long-term neurodevelopment
      outcome in twin-twin transfusion syndrome treated with laser surgery. METHODS:
      Twin-twin transfusion syndrome cases treated with laser surgery at three European
      centers from August 2000 to December 2005 were included in this case-control
      study. Neurological, mental, and psychomotor development (using the Bayley Scales
      of Infant Development, 2nd edition) was evaluated at 2 years of age. RESULTS: A
      total of 212 twin-twin transfusion syndrome pregnancies were treated with laser
      surgery during the study period. Overall mortality rate was 30% (129 of 424).
      Seventeen children (6%) were lost to follow-up. Long-term outcome was assessed in
      278 infants. The incidence of neurodevelopment impairment was 18% (50 of 278).
      Four risk factors were found to be significantly associated with increased risk
      for neurodevelopment impairment: greater gestational age at laser surgery (odds
      ratio [OR] 1.30, 95% confidence interval [CI] 1.00-1.69; P=.05), higher Quintero
      stage (OR 3.55 for each increment in stage, 95% CI 1.07-11.82, P=.04), lower
      gestational age at birth (OR 1.39 for each week, 95% CI 1.06-1.81; P=.01), and
      lower birth weight (OR 1.18 for each 100-g decrease, 95% CI 1.05-1.32; P<.01). In
      a multivariable analysis, lower gestational age at birth was the only factor
      independently associated with neurodevelopmental impairment (OR 1.33 for each
      week, 95% CI 1.05-1.67, P=.02). CONCLUSION: Neurodevelopment impairment in twin-
      twin transfusion syndrome survivors treated with laser surgery is associated with
      advanced gestational age at laser surgery, low gestational age at birth, low
      birth weight, and high Quintero stage. LEVEL OF EVIDENCE: II.

PMID- 19155908
TI  - Complication and reoperation rates after apical vaginal prolapse surgical repair:
      a systematic review.
AB  - OBJECTIVE: To compare postoperative complication and reoperation rates for
      surgical procedures correcting apical vaginal prolapse. DATA SOURCES: Eligible
      studies were selected through an electronic literature search covering January
      1985 to January 2008 using PubMed, the Cochrane Central Register of Controlled
      Trials, the Cochrane Database of Systematic Reviews, and the Database of
      Abstracts of Reviews and Effects. METHODS OF STUDY SELECTION: Only clinical
      trials and observational studies addressing apical prolapse repair and recurrence
      or complication rates were included. The search was restricted to original
      articles published in English with 50 or more participants and a follow-up period
      of 3 months or longer. Oral platform and poster presentations from the American
      Urogynecological Society, the Society for Gynecologic Surgeons, the International
      Urogynecological Association, and the International Continence Society from
      January 2005 to December 2007 were hand searched to determine whether they were
      eligible for inclusion. TABULATION, INTEGRATION, AND RESULTS: Procedures were
      separated into three groups: traditional vaginal surgery, sacral colpopexy, and
      vaginal mesh kits. Complications were classified using the Dindo grading system.
      Weighted averages were calculated for each Dindo grade, complication, and
      reoperation. Dindo grade IIIa (433/3,425 women) and IIIb (245/3,425) rates were
      highest in the mesh kit group owing to higher rates of mesh erosion (198/3,425)
      and fistulae (8/3,425). Reoperation rates for prolapse recurrence were highest in
      the traditional vaginal surgery group (308/7,827). The total reoperation rate was
      greatest in the mesh kit group (291/3, 425, 8.5%). CONCLUSION: The rate of
      complications requiring reoperation and the total reoperation rate was highest
      for vaginal mesh kits despite a lower reoperation rate for prolapse recurrence
      and shorter overall follow-up.

PMID- 19155909
TI  - Low-dose oral misoprostol for induction of labor: a systematic review.
AB  - OBJECTIVE: To estimate the efficacy and safety of low-dose oral misoprostol
      compared with dinoprostone (PGE2), vaginal misoprostol, and oxytocin for labor
      induction in women with a viable fetus. DATA SOURCES: We conducted electronic
      database searches of PubMed, MEDLINE, EMBASE, and the Cochrane Library for
      articles published before January 2008 using the keywords misoprostol, labor,
      induction, randomized controlled trials, dinoprostone, oxytocin, pregnancy, and
      maternal and fetal side effects. METHODS OF STUDY SELECTION: We included
      randomized controlled trials comparing 20-25 micrograms oral misoprostol with
      vaginal misoprostol, dinoprostone or oxytocin given to women at 32-42 weeks of
      gestation for labor induction. From 401 citations identified, results from nine
      studies were finally analyzed using the Review Manager software. Relative risk
      (RR) and 95% confidence intervals (CIs) were calculated using fixed and random
      effects models. TABULATION, INTEGRATION, AND RESULTS: Nine articles with 2,937
      women met the inclusion criteria. The five trials comparing oral misoprostol and
      dinoprostone showed significantly fewer women requiring cesarean delivery in the
      misoprostol group (20% compared with 26%; RR 0.82, 95% CI 0.71-0.96). There were
      no statistically significant differences in risks of uterine hyperstimulation or
      need for oxytocin augmentation. Two trials compared oral with vaginal low-dose
      misoprostol. Women using oral misoprostol were significantly less likely to
      experience uterine hyperstimulation with fetal heart rate changes (2% compared
      with 13%; RR 0.19, 95% CI 0.08-0.46), but there were no significant differences
      in other outcomes. CONCLUSION: Low-dose oral misoprostol solution (20 micrograms)
      administered every 2 hours seems at least as effective as both vaginal
      dinoprostone and vaginal misoprostol, with lower rates of cesarean delivery and
      uterine hyperstimulation, respectively.

PMID- 19155910
TI  - The accuracy of risk scores in predicting ovarian malignancy: a systematic
      review.
AB  - OBJECTIVE: To perform a systematic review of the literature on the accuracy of
      prediction models in the preoperative assessment of adnexal masses. DATA SOURCES:
      Studies were identified through the MEDLINE and EMBASE databases from inception
      to March 2008. The MEDLINE search was performed using the keywords ["ovarian
      neoplasms"[MeSH] NOT "therapeutics"[MeSH] AND "model"] and ["ovarian
      neoplasms"[MeSH] NOT "therapeutics"[MeSH] AND "prediction"]. The Embase search
      was performed using the keywords [ovary tumor AND prediction], [ovary tumor AND
      Mathematical model], and [ovary tumor AND statistical model]. METHODS OF STUDY
      SELECTION: The search detected 1,161 publications; from the cross-references,
      another 116 studies were identified. Language restrictions were not applied.
      Eligible studies contained data on the accuracy of models predicting the risk of
      malignancy in ovarian masses. Models were required to combine at least two
      parameters. TABULATION, INTEGRATION, AND RESULTS: Two independent reviewers
      selected studies and extracted study characteristics, study quality, and test
      accuracy. There were 109 accuracy studies that met the selection criteria.
      Accuracy data were used to form two-by-two contingency tables of the results of
      the risk score compared with definitive histology. We used bivariate meta
      analysis to estimate pooled sensitivities and specificities and to fit summary
      receiver operating characteristic curves.Studies included in our analysis
      reported on 83 different prediction models. The model developed by Sassone was
      the most evaluated prediction model. All models has acceptable sensitivity and
      specificity. However, the Risk of Malignancy Index I and the Risk of Malignancy
      Index II, which use the product of the serum CA 125 level, an ultrasound scan
      result, and the menopausal state, were the best predictors. When 200 was used as
      the cutoff level, the pooled estimate for sensitivity was 78% for a specificity
      of 87%. CONCLUSION: Based on our review, the Risk of Malignancy Index should be
      the prediction model of choice in the preoperative assessment of the adnexal
      mass.

PMID- 19155911
TI  - Smaller pieces of the hysterectomy pie: current challenges in resident surgical
      education.
AB  - Residents in obstetrics and gynecology are increasingly confronted with a wider
      range of techniques that must be mastered to perform hysterectomy, including
      abdominal, vaginal, laparoscopic, and robotic approaches. This is accompanied by
      a decrease in the number of hysterectomies performed annually. Possible solutions
      to the dilemma created for surgical teaching includes a comprehensive program
      evaluating surgical competency by establishing numbers needed to achieve
      competency for specific major procedures.

PMID- 19155912
TI  - Pertussis disease in new mothers: effect on young infants and strategies for
      prevention.
AB  - Pertussis, or whooping cough, is a major public health problem in the United
      States, with the incidence of disease and its associated complications having
      significantly increased in the adolescent and adult populations. These
      populations serve as the major transmission source of the disease to young
      infants, a group that is at the highest risk of severe morbidity and mortality
      from the disease. Studies have shown that new parents, especially mothers, are
      the source of disease transmission in more than 50% of the cases. Tetanus toxoid,
      reduced diphtheria toxoid, and acellular pertussis booster vaccines (Tdap) are
      licensed for use in adolescent and adult populations. The Centers for Disease
      Control and Prevention (CDC) recommends that the Tdap vaccine be given to
      postpartum women as soon as possible after delivery and before hospital discharge
      to protect them and their newborns against pertussis disease. The American
      College of Obstetricians and Gynecologists recommends that its membership follow
      the CDC recommendations. This article includes a further discussion of the
      rationale for this recommendation and provides possible strategies for vaccine
      implementation.

PMID- 19155913
TI  - Performing a fetal anatomy scan at the time of first-trimester screening.
AB  - Over the past decade, prenatal diagnosis has shifted rapidly from the second
      trimester into the first trimester. Although the nuchal-translucency scan may
      detect a small proportion of fetal structural malformations, fetal anatomy is not
      routinely assessed until the fetal anatomical survey is performed in the second
      trimester between 18 and 22 weeks. The recent development of high-frequency
      transvaginal ultrasound transducers has led to vastly improved ultrasound
      resolution and improved visualization of fetal anatomy earlier in gestation.
      Several pilot studies of a first-trimester anatomic survey have reported
      detection rates comparable with those achieved in the routine second-trimester
      anatomic survey. As advanced ultrasound technology becomes more available, there
      is an urgent need to evaluate the diagnostic ability of a first-trimester
      anatomic survey and to determine the role of a first-trimester anatomic survey in
      the current screening paradigm.

PMID- 19155914
TI  - Fetal intervention: providing reasonable access to quality care.
AB  - Interest in fetal intervention has become widespread in recent years. Laser
      therapy for the treatment of severe twin-twin transfusion alone has been the
      subject of more than 100 peer-reviewed articles in the past 3 years. Significant
      issues have arisen that affect the availability of these new therapies in the
      United States. Formal training fellowships have yet to be established. Questions
      as to the ultimate number of treatment centers that are required to provide
      reasonable access should be addressed. The establishment of research networks to
      evaluate new fetal therapies through randomized clinical trials would appear
      paramount to the advancement of the field.

PMID- 19155915
TI  - Prevention and management of surgical site infections in morbidly obese women.

PMID- 19155916
TI  - Medications in pregnancy and lactation: Part 2. Drugs with minimal or unknown
      human teratogenic effect.
AB  - This is the second of a two-part series on the use of medication during pregnancy
      and lactation. Pregnancy risk factors together with an increased incidence of
      chronic diseases and the rise in mean maternal age predict an increase in
      medication use during gestation. However, as highlighted in the first installment
      of this series, relatively few medications have specifically been tested for
      safety and efficacy during pregnancy, and, therefore, responses to those
      inquiries can be uninformed and inaccurate. Whereas the first installment
      provided new insight into the nature of medications with known human teratogenic
      effects, this part concentrates on drugs with minimal or no known human
      teratogenic effect. It is important that clinicians become familiar with all of
      the aspects of the drugs they prescribe, in addition to the controversies
      surrounding them, through consultation with maternal-fetal medicine specialists
      and through references and Web sites providing up-to-date information in an
      effort to promote safer prescribing practices.

PMID- 19155918
TI  - Evaluating the rate and risk factors for fetal loss after chorionic villus
      sampling.

PMID- 19155919
TI  - ACOG Practice Bulletin No. 100: Critical care in pregnancy.

PMID- 19155920
TI  - ACOG Practice Bulletin No. 101: Ultrasonography in pregnancy.

PMID- 19155921
TI  - ACOG Committee Opinion No. 426: The role of transvaginal ultrasonography in the
      evaluation of postmenopausal bleeding.
AB  - The clinical approach to postmenopausal bleeding requires prompt and efficient
      evaluation to exclude or diagnose carcinoma. Women with postmenopausal bleeding
      may be assessed initially with either endometrial biopsy or transvaginal
      ultrasonography;this initial evaluation does not require performance of both
      tests.Transvaginal ultrasonography can be useful in the triage of patients in
      whom endometrial sampling was performed but tissue was insufficient for
      diagnosis. When transvaginal ultrasonography is performed for patients with
      postmenopausal bleeding and an endometrial thickness of less than or equal to 4
      mm is found, endometrial sampling is not required. Meaningful assessment of the
      endometrium by ultrasonography is not possible in all patients. In such cases,
      alternative assessment should be completed. When bleeding persists despite
      negative initial evaluations, additional assessment usually is indicated.

PMID- 19155922
TI  - ACOG Committee Opinion No. 427: Misoprostol for postabortion care.
AB  - The World Health Organization estimates that 67,000 women, mostly in developing
      countries, die each year from untreated or inadequately treated abortion
      complications. Postabortion care, a term commonly used by the international
      reproductive health community, refers to a specific set of services for women
      experiencing problems from all types of spontaneous or induced abortion. There is
      increasing evidence that misoprostol is a safe, effective, and acceptable method
      to achieve uterine evacuation for women needing postabortion care. To reduce
      maternal mortality, availability of postabortion care services must be increased.
      Misoprostol must be readily available especially for women who do not otherwise
      have access to postabortion care. Nurses and midwives can safely provide first
      line postabortion care services, including in outpatient settings,provided they
      receive appropriate training and support. Access to contraception and safe
      abortion services prevents complications from unsafe abortion and decreases the
      need for postabortion care. It is much less expensive and far better for women's
      health to prevent the problem of unsafe abortion rather than to treat resulting
      complications.

PMID- 19155923
TI  - ACOG Committee Opinion No. 428: Legal status: health impact for lesbian couples.
AB  - Women in same-sex relationships encounter barriers to health care that include
      concerns about confidentiality and disclosure, discriminatory attitudes and
      treatment,limited access to health care and health insurance, and often a limited
      understanding as to what their health risks may be. Lesbians and their families
      also are adversely affected by the lack of legal recognition of their
      relationships. Tangible harm comes from the lack of financial and health care
      protections that are granted to legal spouses, and children are harmed by the
      lack of protections afforded married families. The American College of
      Obstetricians and Gynecologists endorses equitable treatment for lesbians and
      their families, not only for direct health care needs but also for indirect
      health care issues;this should include the same legal protections afforded
      married couples.

PMID- 19155924
TI  - Fetoscopic tracheal occlusion for previable rupture of the membranes:
      recklessness or heroic medical innovation?

PMID- 19155926
TI  - Posterior axillary sling traction: another empiric technique for shoulder
      dystocia alleviation?

PMID- 19155925
TI  - Vasopressin: if some is good, is more better?

PMID- 19155927
TI  - Life-saving effects of fetal tracheal occlusion on pulmonary hypoplasia from
      preterm premature rupture of membranes.
AB  - BACKGROUND: Preterm premature rupture of membranes before 22 weeks of gestation
      may result in severe fetal pulmonary hypoplasia. Fetoscopic tracheal balloon
      occlusion might result in catch-up pulmonary growth. CASE: After preterm
      premature rupture of membranes at 16 weeks of gestation, magnetic resonance
      imaging at 26 0/7 weeks showed a fetal lung volume of 13 mL and pulmonary blood
      flow hardly could be detected. Fetoscopic tracheal balloon occlusion was
      performed at 27 6/7 weeks; within 6 days, fetal lung volume increased to 70 mL
      and lung blood flow normalized. The fetus was delivered electively at 28 6/7
      weeks. Six hours after delivery, the neonate required only 21% oxygen and was
      extubated after 55 hours. CONCLUSION: Short-term fetoscopic tracheal balloon
      occlusion may result in rapid normalization of fetal lung volume and blood flow
      in fetuses with life-threatening pulmonary hypoplasia from preterm premature
      rupture of membranes before 22 weeks of gestation.

PMID- 19155928
TI  - Bradycardia and cardiac arrest caused by intramyometrial injection of vasopressin
      during a laparoscopically assisted myomectomy.
AB  - BACKGROUND: Vasopressin is often used locally to reduce blood loss during
      surgery. The use of a local infiltration of a low concentration of vasopressin,
      less than 0.05-0.3 units/mL, has been considered to be safe. The use of low-dose
      vasopressin is not free of side effects, and it can also sometimes cause lethal
      complications. CASE: In a healthy woman with multiple uterine myomas, we
      experienced a case of sudden cardiac arrest immediately after the intramyometrial
      injection of vasopressin at a total dose of 11 units (0.2 units/mL). The patient
      was successfully resuscitated. CONCLUSION: Local intramyometrial infiltration of
      low-dose vasopressin may cause lethal cardiopulmonary complications.

PMID- 19155929
TI  - Posterior axilla sling traction: a technique for intractable shoulder dystocia.
AB  - BACKGROUND: We describe a new method for delivery of intractable shoulder
      dystocia with posterior axilla sling traction. CASES: Two cases of shoulder
      dystocia after intrauterine death are described where routine methods of delivery
      were unsuccessful. In each case, a soft plastic suction catheter was folded in
      half over the operator's fingertip and digitally inserted around the posterior
      shoulder, under the axilla, and retrieved with the other hand to create a sling
      to which traction was applied. The posterior shoulder, followed by the anterior
      shoulder, was easily delivered. CONCLUSION: Posterior axilla sling traction may
      overcome intractable shoulder dystocia and avoid more traumatic procedures in
      fetal death.

PMID- 19155930
TI  - Uterine arteriovenous fistula as a long-term complication of hysterectomy:
      presentation and management.
AB  - BACKGROUND: A rare complication of hysterectomy is the formation of a high-flow
      fistula between the uterine artery and uterine vein. Historically, these lesions
      were treated surgically. CASE: Two women with histories including hysterectomy
      presented with symptoms and physical examination signs suggestive of uterine
      arteriovenous fistulae. After arteriographic diagnostic confirmation, both women
      were treated successfully with endovascular embolization. CONCLUSION: A palpable,
      pulsatile pelvic mass in a patient with a history of hysterectomy should prompt
      referral for radiographic evaluation of a possible pelvic arteriovenous fistula.
      Selective arterial embolization may be considered an option for treatment of this
      entity.

PMID- 19155931
TI  - Stercoral perforation of the colon with favorable pregnancy outcome.
AB  - BACKGROUND: Stercoral perforation of the colon is a rarely reported disease with
      high mortality rate. Our literature review identified one prior case reported
      during pregnancy, with mortality in both mother and infant. CASE: A nulliparous
      female presented at 36 weeks of gestation with fever, tachycardia, and severe
      abdominal pain. She delivered by cesarean when purulent ascites and stercoral
      perforation of the sigmoid colon were discovered. After a sigmoid resection with
      end colostomy, she and her infant recovered uneventfully. CONCLUSION: Stercoral
      perforation of the colon is rare in pregnancy. Prompt surgical treatment is
      necessary. Surgical exploration may be warranted in the pregnant patient with
      unexplained abdominal pain.

PMID- 19155932
TI  - Spontaneous severe ovarian hyperstimulation syndrome in successive pregnancies
      with successful outcomes.
AB  - BACKGROUND: Ovarian hyperstimulation syndrome is a known complication of ovarian
      stimulation, particularly with injectable gonadotropins. Spontaneous ovarian
      hyperstimulation is rare and often involves a conformational change in the
      follicle-stimulating hormone receptor, increasing its binding with human
      chorionic gonadotropin or thyroid-stimulating hormone. Few data are available
      regarding the management or outcomes of spontaneous ovarian hyperstimulation
      syndrome. CASE: A 23-year-old white female without history of infertility
      treatment presented with ovarian hyperstimulation syndrome in two pregnancies.
      The patient was treated by paracentesis catheter placement and albumin
      replacement. She had regression of symptoms between 11 weeks and 12 weeks of
      gestation in both pregnancies and delivered healthy term infants. CONCLUSION: The
      case presented involves a patient with spontaneous severe ovarian
      hyperstimulation syndrome in two successive pregnancies. The patient was managed
      aggressively with paracentesis and albumin replacement resulting in two
      successful pregnancies.

PMID- 19155933
TI  - Complete eversion of the urinary bladder: presentation, review, and algorithm for
      management.
AB  - BACKGROUND: Complete eversion of the urinary bladder is a rare problem that
      presents a serious management challenge. Currently no standard treatment
      recommendations exist for management. We describe our experience with bladder
      eversion and present an algorithm for treatment. CASE: An elderly, multiparous
      woman presented with complete bladder eversion after partial colpocleisis. Her
      bladder was reduced by a combined suprapubic and perineal approach with cystopexy
      to the anterior abdominal wall. CONCLUSION: Multiparous postmenopausal women
      appear to be at highest risk for complete bladder eversion. External
      transurethral reduction is sometimes successful, but most cases require
      laparotomy.

PMID- 19155934
TI  - Successful management of second-trimester postabortion hemorrhage with an
      intrauterine tamponade balloon.
AB  - BACKGROUND: Legally induced abortion is a safe procedure. However, hemorrhage is
      a significant cause of abortion-related morbidity and mortality. We describe a
      case in which a uterine tamponade balloon was successfully used to control a
      second-trimester postabortion hemorrhage. CASE: A gravida 1 para 0 woman
      underwent dilation and evacuation at 18 weeks of gestation for fetal aneuploidy.
      Her procedure was complicated by intraoperative hemorrhage not resulting from
      uterine atony. This was successfully managed by tamponade with a large
      intrauterine balloon. CONCLUSION: Uterine balloon tamponade should be considered
      in the management of second-trimester postabortion hemorrhage unresponsive to
      medical therapy.

PMID- 19155935
TI  - Group a Streptococcus causing necrotizing fasciitis and toxic shock syndrome
      after medical termination of pregnancy.
AB  - BACKGROUND: Group A Streptococcus is an aerobic gram-positive bacteria known to
      cause cutaneous infections. Invasive infections can lead to toxic shock syndrome
      with multiorgan failure and mortality rates of 25-48%. CASE: A healthy, young
      woman developed necrotizing fasciitis, myonecrosis, and toxic shock syndrome
      after an elective medical termination of pregnancy. This patient had confirmed
      group A Streptococcus on blood cultures and underwent surgical debridement. After
      aggressive surgical treatment, below-the-knee amputation, and antibiotic therapy,
      the patient survived. CONCLUSION: This case demonstrates the need for prompt
      recognition and treatment of necrotizing fasciitis/toxic shock syndrome.

PMID- 19155936
TI  - Urethral prolapse in a premenarchal Asian girl.
AB  - BACKGROUND: Urethral prolapse is an uncommon condition characterized by complete
      circular eversion of the urethral mucosa through the external meatus. CASE: We
      present the case of a 9-year-old Asian girl who presented with 3 days of vaginal
      spotting and a painless vulvar mass. After several unsuccessful attempts of
      manual reduction, surgery was performed. As a result, the patient had no
      recurrence or meatal stenosis at the 6-month follow-up. CONCLUSION: Urethral
      prolapse can be clinically diagnosed without laboratory or radiographic
      evaluation by demonstrating edematous tissue that surrounds the meatus
      circumferentially. It should not be confused with other causes of vaginal
      bleeding, including sexual abuse.

PMID- 19155937
TI  - Liver transplantation for spontaneous intrapartum rupture of a hepatic adenoma.
AB  - BACKGROUND: Hepatocellular adenomas can rupture during pregnancy with high fetal
      and maternal associated mortality. CASE: A primipara underwent an emergency
      cesarean delivery at 37 weeks of gestation for abruptio placentae. A few hours
      later she developed hemorrhagic shock, and laparotomy revealed the rupture of the
      right lobe of the liver. Bleeding was controlled with perihepatic gauze packing
      and she was transferred to a transplant center for emergency orthotopic liver
      transplantation. Histologic examination revealed the presence of an intrahepatic
      hematoma caused by the rupture of a 12-cm hepatocellular adenoma. At 48 months
      after transplantation she and her infant were both in good condition. CONCLUSION:
      Emergency orthotopic liver transplantations performed for acute rupture of an
      hepatocellular adenoma represents a valid therapy provided that bleeding can be
      controlled long enough to locate a suitable donor.

PMID- 19155938
TI  - Ancient schwannoma of the vulva.
AB  - BACKGROUND: Ancient schwannoma, a variant of schwannoma (previously termed
      neurilemoma), arises from the Schwann cells of the nerve sheath. It presents with
      swelling, pain, or paresthesia. CASE: A 53-year-old woman presented with a
      history of a left vulvar swelling, which had been present for many years. The
      tumor was slowly increasing in size and affected activities such as sitting and
      walking. Occasionally, she experienced a burning sensation at the site of the
      swelling. Surgical excision was undertaken, and histology demonstrated an ancient
      schwannoma. CONCLUSION: The characteristic histological appearance seen in
      ancient schwannoma should prevent the erroneous diagnosis of a malignant tumor.
      Malignant change is exceedingly rare. Treatment is complete surgical excision.

PMID- 19155939
TI  - Placenta percreta masquerading as an acute abdomen.
AB  - BACKGROUND: The incidence of placenta percreta has been on the rise during the
      past decades, coincident with the increase in cesarean deliveries. The diagnosis
      of this potentially life-threatening complication is difficult, especially when
      it masquerades as other severe complications of pregnancy. CASE: A woman with one
      previous cesarean delivery presented at 28 weeks of gestation with right upper
      quadrant pain. Laparotomy revealed an intraperitoneal hemorrhage from a
      protrusion of the placenta at the previous uterine incision remote from the site
      of pain presentation. The fetus was delivered, and a hysterectomy was performed
      with subsequent good recovery. Pathology confirmed placenta percreta. CONCLUSION:
      The presentation of an acute abdomen with symptoms remote from the site of
      pathology in the third trimester masked the diagnosis of placenta accreta. When a
      clear diagnosis cannot be established, operative exploration must be considered.

PMID- 19155940
TI  - A maternal and perinatal mortality in pregnancy complicated by the kyphoscoliotic
      form of Ehlers-Danlos syndrome.
AB  - BACKGROUND: Ehlers-Danlos syndrome is a group of inherited connective tissue
      diseases demonstrating autosomal-dominant, autosomal-recessive, and X-linked
      inheritance patterns. The diagnosis can be established by clinical, biochemical,
      and genetic findings. CASE: Our nulliparous patient presented with an unspecified
      diagnosis of Ehlers-Danlos syndrome. Laboratory testing confirmed the
      kyphoscoliotic type. Based on clinical and phenotypic similarities with the
      vascular type of Ehlers-Danlos syndrome, termination was advised. Minor trauma in
      the third trimester led to delivery of a stillborn fetus, which was followed by
      disseminated intravascular coagulopathy and death of the mother. Maternal autopsy
      revealed that there had been a spontaneous rupture of the right iliac artery.
      CONCLUSION: Practitioners should be aggressive in recommending effective birth
      control in patients with the kyphoscoliotic form of Ehlers-Danlos syndrome. In
      cases of established pregnancy, patients should be made fully aware of their
      risks of death and severe complications.

PMID- 19155941
TI  - Persistent low levels of beta-hCG in a patient with recurrent pregnancy loss.
AB  - BACKGROUND: A subset of women with persistent low levels of beta-hCG have
      undergone potentially harmful treatments despite no evidence of pregnancy or
      gestational trophoblastic neoplasia. CASE: A 37-year-old woman with a history of
      recurrent pregnancy loss presented with persistent low levels of beta-hCG. She
      was treated for ectopic pregnancy and retained products and was later suspected
      of having a malignancy. However, further evaluation of her human chorionic
      gonadotropin led to a diagnosis of quiescent gestational trophoblastic disease.
      CONCLUSION: A diagnosis of quiescent gestational trophoblastic disease should be
      considered in all patients who present with persistent low levels of beta-hCG,
      including those with recurrent pregnancy loss.

PMID- 19155942
TI  - Sonography of lower uterine segment thickness and prediction of uterine rupture.
AB  - BACKGROUND: Sonographic evaluation of the lower uterine segment was undertaken to
      study the degree of thinning and, thus, to predict uterine rupture. However, the
      best measuring technique and recommended cutoff values remain controversial.
      CASE: Sonographic evaluation of the lower uterine segment at 36 weeks of
      gestation in a 31-year-old patient with prior low transverse cesarean delivery
      revealed a full thickness of 3.6 mm and a myometrial layer of 1.1 mm.
      Nevertheless, the patient experienced a large uterine rupture during a trial of
      labor at term. CONCLUSION: In this case, there was a discrepancy between the full
      thickness and the myometrial layer, which could be representative of the lower
      uterine segment resistance. Such a case emphasizes the need for a consensus on
      sonographic measuring techniques for the prediction of uterine rupture.

PMID- 19155943
TI  - Ureterocele misdiagnosed as pelvic inflammatory disease in an adolescent.
AB  - BACKGROUND: Acute pelvic pain in reproductive-aged women presents a diagnostic
      challenge. In the case that follows, we report the management of a patient
      initially misdiagnosed with pelvic inflammatory disease. CASE: A 14-year-old
      nulligravida who presented with acute pelvic pain was diagnosed with pelvic
      inflammatory disease and possible tuboovarian abscess. Despite treatment with
      broad-spectrum parenteral antibiotics, the patient remained febrile with
      persistent pelvic pain. Com-puted tomography revealed a duplicated right
      collecting system with the upper pole of the kidney drained by a markedly
      dilated, tortuous ureter. An infected ureterocele was identified and incised
      during cystoscopy. CONCLUSION: An infected ureterocele was misdiagnosed as pelvic
      inflammatory disease. In patients with acute pelvic pain who do not respond to
      appropriate interventions, it is important to consider alternative diagnoses.

PMID- 19155944
TI  - Uterine diverticulum.
AB  - BACKGROUND: Uterine diverticula complicating pregnancy rarely are reported and
      should be differentiated from sacculation of pregnancy and other pelvic masses.
      CASE: A primigravida presented for a routine second-trimester anatomical survey
      ultrasound examination at 22 weeks of gestation. She initially was thought to
      have a bicornuate, bicolic uterus with bulging membranes. However, on
      examination, one normal-appearing cervix was found, and no membranes were
      visible. Magnetic resonance imaging demonstrated a posterolateral uterine
      diverticulum. At 31 weeks of gestation, she had premature rupture of membranes
      and onset of labor. Delivery by cesarean was performed, and the presence of a
      uterine diverticulum was confirmed. CONCLUSION: Uterine diverticula are rare
      anomalies in the pregnant uterus and should be considered in the differential
      diagnosis of a fluid-filled pelvic mass. With close observation, successful
      pregnancy outcome can be achieved.

PMID- 19155945
TI  - Sudden fetal death in intrahepatic cholestasis of pregnancy.
AB  - BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with an increased
      risk of fetal death. The mechanism of death is unknown. CASES: The first case
      involved a young primipara with pruritus and a bile acid concentration of 79
      mumol/dL. While undergoing fetal heart rate monitoring, the fetus had a prolonged
      deceleration resulting in intrauterine death. The second case involved a young
      multipara with cholestasis who received ursodeoxycholic acid. Her bile acid
      concentration improved to13 micromol/dL. At 34 weeks of gestation, she had
      uterine contractions with prolonged decelerations resulting in delivery of her
      fetus with Apgar scores of 0, 0, and 5 at 1, 5, and 10 minutes, respectively.
      CONCLUSION: Fetal death from intrahepatic cholestasis of pregnancy can be abrupt
      and not reliably predicted by the characteristics of the fetal heart rate
      tracing.

PMID- 19155946
TI  - Spontaneous spinal epidural hematoma in pregnancy associated with using low
      molecular weight heparin.
AB  - BACKGROUND: Spontaneous epidural hematoma of the spine occurring in pregnancy is
      uncommon and may result in permanent damage if not promptly treated. The use of
      low molecular weight heparin may be a risk factor for this condition. CASE: We
      describe the case of a woman who presented at 27 weeks of gestation with
      progressive back pain and leg weakness while being treated with low molecular
      weight heparin. A magnetic resonance imaging (MRI) examination of the spine
      revealed an epidural hematoma, which was surgically treated. A cesarean delivery
      was performed at 36 weeks of gestation. CONCLUSION: Spontaneous epidural hematoma
      of the spine may present in pregnant patients using low molecular weight heparin.
      The onset of neurologic symptoms and pain in these gravidas should be evaluated
      with MRI. Expeditious surgery is almost always the best treatment option.

PMID- 19155947
TI  - Pregnancy in true hermaphrodites and all male offspring to date.
AB  - BACKGROUND: There are 11 reported cases of pregnancy in true hermaphrodites, but
      none with advanced genetic testing. All known fetuses have been male. CASE: A
      true hermaphrodite with a spontaneous pregnancy prenatally known to have a
      remaining portion of a right ovotestis, delivered a male neonate. The mother has
      a 46, XX karyotype with polymerase chain reaction demonstrating low levels of the
      Yq12 sequence. Postpartum androgen levels were normal. CONCLUSION: Partial
      removal of testicular tissue may enhance fertility in hermaphrodites, and there
      may be a genetic basis for the progeny to be male.

PMID- 19155948
TI  - Rupture of ectopic pregnancy with negative serum beta-hCG leading to hemorrhagic
      shock.
AB  - BACKGROUND: Rupture of a fallopian tube caused by ectopic pregnancy may have
      serious consequences including hemorrhagic shock. The diagnosis of ectopic
      pregnancy is based on the demonstration of pregnancy using serum beta-hCG assays.
      Thus, a negative test usually allows the exclusion of the diagnosis of ectopic
      pregnancy. CASE: We present an unusual case of ectopic pregnancy resulting in
      hemorrhagic shock despite negative results for serum beta-hCG tests. Computed
      tomography and ultrasound scans revealed hemoperitoneum and a right adnexal mass.
      Medical management and laparoscopic salpingectomy allowed for a favorable
      outcome. CONCLUSION: This case illustrates the potential for an ectopic pregnancy
      to rupture with undetectable serum beta-hCG levels. Further, it illustrates the
      helpful role of imaging exams in diagnosing a patient with unstable hemodynamic
      status.

PMID- 19155949
TI  - Pseudoaneurysm of the uterine artery after cesarean delivery: management with
      superselective arterial embolization.
AB  - BACKGROUND: Uterine artery pseudoaneurysm is a rare but serious complication of
      pelvic surgery. Cesarean delivery is the most common cause. CASE: We report a
      case of postpartum pelvic hemorrhage after cesarean delivery. A false aneurysm of
      the uterine artery was found by color Doppler ultrasonography and multislice
      spiral computed tomography. Arteriography confirmed the diagnosis. Superselective
      coil embolization of the aneurysm sac was achieved using the packing technique.
      The main uterine artery was preserved and the postprocedural course was
      uneventful. CONCLUSION: Color Doppler ultrasonography and computed tomography
      were useful for the early diagnosis of uterine artery pseudoaneurysm. Primary
      transcatheter arterial embolization controlled bleeding without compromising
      reproductive potential.

PMID- 19155950
TI  - Vulvovaginal pellagra and lichen sclerosus complicating carcinoid syndrome.
AB  - BACKGROUND: Pellagra is a rare clinical syndrome caused by niacin deficiency, and
      although most commonly nutritional in origin, may be secondary to carcinoid
      syndrome. CASE: A premenopausal nulliparous woman with metastatic carcinoid tumor
      developed isolated vulvovaginal manifestations characterized by well-demarcated
      symmetrical vulvar erythema, mild scaling, ulcerations, and dyspareunia.
      Tryptophan levels were low. Treatment with nicotinamide resulted in dramatic
      improvement; however, after 2 years of effective treatment, she developed lichen
      sclerosus. CONCLUSION: Patients with carcinoid tumor presenting chronic vulvar
      lesions should be evaluated for pellagra. Subsequent development of lichen
      sclerosus at the site of vulvar dermatosis may be a feature of the "Koebner
      phenomenon," which describes appearance of lichen sclerosus in scarred areas or
      sites prone to friction.

PMID- 19155951
TI  - Hemolysis and elevated transaminases imitating severe preeclampsia.
AB  - BACKGROUND: Illnesses coincident with pregnancy may present similarly to
      preeclampsia or may be mistaken for severe preeclampsia or hemolysis, elevated
      liver enzymes, low platelets (HELLP) syndrome. Distinguishing these imitators
      from preeclampsia is important to allow for appropriate treatment and to avoid
      unnecessary delivery. CASE: A primigravida at 32 2/7 weeks of gestation
      transferred to our institution with flu-like symptoms, anemia, jaundice, and
      elevated liver function tests. The team caring for her was concerned about HELLP
      or acute fatty liver. After extensive workup, she was found to have a cold
      agglutinin. Her laboratory test results improved, and she was discharged
      undelivered with a presumptive diagnosis of cold agglutinin autoimmune hemolytic
      anemia. CONCLUSION: When patients present with atypical features of HELLP
      syndrome, clinicians should take time to consider other "imitators of
      preeclampsia" before rapidly progressing to delivery to avoid inappropriate
      treatment of the disorder.

PMID- 19155952
TI  - Cervical obstruction complicating second-trimester abortion: treatment with
      misoprostol.
AB  - BACKGROUND: Cervical cone biopsy or loop electrosurgical excision procedures
      (LEEP) may lead to cervical scarring, agglutination, or stenosis. Leiomyomas may
      also obstruct the lower uterine segment such that instruments cannot be passed
      from the vagina to the gestation. CASE: Two women requested second trimester
      abortion. Both women had undergone cervical LEEP. In addition, one woman had a 10
      cm leiomyoma, which seemed to be obstructing the lower segment. In both, the
      external cervical os was essentially obliterated. After administration of
      misoprostol, the cervix softened markedly in 18-24 hours. In both women, the
      cervix dilated readily and allowed dilation and evacuation of the uterus.
      CONCLUSION: Misoprostol resulted in the ability to evacuate the uterus vaginally,
      in a situation that might have otherwise resulted in hysterotomy.

PMID- 19155953
TI  - Cervical cancers after human papillomavirus vaccination.
AB  - BACKGROUND: Current randomized clinical trials have shown that the quadrivalent
      human papillomavirus (HPV) vaccine can reduce the morbidity of precancerous
      lesions associated with HPV infection of vaccine-related subtypes. However, to
      date, there is no definite evidence showing the vaccine reduces the incidence of
      invasive cervical carcinoma. CASES: We present two cases--one young, vaccinated
      woman who developed cervical carcinoma that was unrelated to HPV and another who
      developed cervical carcinoma secondary to infection with an HPV subtype not
      covered by the vaccine. Both patients were treated successfully and remained well
      without evidence of cancer. CONCLUSION: Long-term follow-up data are needed to
      evaluate the prophylactic effectiveness of the current HPV vaccine. These cases
      could represent non-vaccine-related HPV infections. Young women must be
      thoroughly counseled about the efficacy and limitations of the vaccine and about
      continuing lifelong screening even after vaccination.

PMID- 19155954
TI  - Intrapartum umbilical cord rupture.
AB  - BACKGROUND: Surveillance and identification of umbilical cord abnormalities is a
      challenging problem in obstetrics. Continuous fetal monitoring during active
      labor helps identify when danger exists for the fetus. CASE: A nullipara
      underwent emergent cesarean delivery for fetal distress and was found to have a
      fetus already separated from the completely torn umbilical cord. The cord was 17
      cm in length, centrally attached, pale, and without bleeding from vasospasm. The
      newborn was initially pale but had a hemoglobin of 17.4 g and survived.
      CONCLUSION: The incidence of rupture of the umbilical cord in utero is rare and
      has little documentation.

PMID- 19155955
TI  - Successful bilateral uterine artery embolization during an ongoing pregnancy.
AB  - BACKGROUND: Uterine arteriovenous malformations are rare, potentially life
      threatening, vascular anomalies. CASE: We report a case of a large arteriovenous
      malformation diagnosed during pregnancy that was successfully treated with
      bilateral uterine artery embolization at 20 weeks of gestation during an ongoing
      pregnancy. The procedure was uncomplicated, did not result in any fetal heart
      rate changes, and, at 35 weeks of gestation, a liveborn male neonate was
      delivered through repeat cesarean without complications. Both the patient and her
      son are doing well more than 2 years after the procedure. CONCLUSION: Uterine
      artery embolization during an ongoing pregnancy did not result in acute
      complications to the fetus or mother.

PMID- 19155956
TI  - Balloon tamponade of hemorrhage after uterine curettage for gestational
      trophoblastic disease.
AB  - BACKGROUND: Uterine bleeding frequently complicates gestational trophoblastic
      disease, particularly after uterine evacuation. Hysterectomy and other procedures
      used to control this bleeding incur significant risk and can limit fertility.
      CASE: We present a case of massive hemorrhage complicating uterine curettage
      performed for metastatic gestational trophoblastic disease. The patient's
      bleeding was controlled successfully by intrauterine tamponade performed using a
      balloon catheter. After catheter removal, she achieved complete disease
      remission. CONCLUSION: Intrauterine balloon catheterization appears to be a
      promising alternative to control uterine hemorrhage and preserve fertility for
      young women undergoing treatment for gestational trophoblastic disease. Its use
      may help avoid invasive interventions, such as hysterectomy and embolization,
      currently used to control hemorrhage after uterine evacuation.

PMID- 19155957
TI  - Complications due to transfusion-related acute lung injury.
AB  - BACKGROUND: Transfusion-related acute lung injury is an underdiagnosed and
      potentially lethal complication of blood transfusion. CASE: A patient underwent
      surgery because of an ectopic pregnancy. During surgery, blood products were
      administered and within minutes she developed pulmonary edema and hypotension.
      Treatment included mechanical ventilation, intravenous fluids, antihistamines,
      inotropic agents, cortisol, and diuretics. It took 4 days for the pulmonary edema
      to resolve and the patient to recover. Analysis of the donor plasma revealed
      human leukocyte antigen antibodies against an antigen of the patient. CONCLUSION:
      Although transfusion-related acute lung injury is usually self-limiting and most
      patients will recover spontaneously, the estimated mortality rate of 5-25%
      warrants prompt identification and adequate action.

PMID- 19155958
TI  - Inguinal hernia containing functioning, rudimentary uterine horn and
      endometriosis.
AB  - BACKGROUND: Inguinal hernia containing uterus and endometriosis is exceedingly
      rare. Most inguinal endometriosis is located at an extrapelvic site near the
      round ligament. We report a case of a patient with inguinal hernia containing
      rudimentary uterine horn and endometriosis. CASE: A young, nulliparous, regularly
      menstruating woman manifested right inguinal mass and pain in the mass during
      menstruation. At 20 years old, she underwent a surgical procedure for right
      inguinal mass. Postoperative pathology findings demonstrated inguinal
      endometriosis. Based on the findings of magnetic resonance imaging, a history of
      inguinal endometriosis, and the occurrence of inguinal pain during menstruation,
      she was diagnosed as having incarcerated inguinal hernia containing anomalous
      uterus and endometriosis. A functioning, noncommunicating, rudimentary uterine
      horn and endometriosis were surgically removed from the hernia sac. Laparoscopy
      demonstrated intraabdominal unicornuate uterus, but no pelvic endometriosis.
      CONCLUSION: Functioning, incarcerated hernia uterus inguinale may be associated
      with mullerian abnormality and concomitant occurrence of inguinal endometriosis.

PMID- 19155960
TI  - Scheduled hysterectomy for second-trimester abortion in a patient with placenta
      accreta.
AB  - BACKGROUND: As cesarean deliveries increase, so does placenta accreta. There is
      little evidence regarding management of patients with known or suspected abnormal
      placentation seeking abortion. CASE: A medically complicated patient with
      evidence of placenta increta on magnetic resonance imaging presented for
      pregnancy termination at 15 weeks of gestation. Scheduled hysterectomy was
      performed to avoid hemorrhage and subsequent complications. The patient did well
      postoperatively; her course was complicated only by a wound infection treated as
      an outpatient. Pathology was consistent with placenta increta. CONCLUSION:
      Placenta accreta has increased 13-fold in the past 30 years. In select patients
      with evidence of abnormal placentation, scheduled hysterectomy for termination of
      pregnancy is an option that may be considered.

PMID- 19155959
TI  - Pyometra after Le Fort colpocleisis resolved with interventional radiology
      drainage.
AB  - BACKGROUND: Le Fort colpocleisis is a surgical treatment option for advanced
      pelvic organ prolapse in women who are willing to give up future vaginal sexual
      function. Pelvic abscess, or pyometra, after Le Fort colpocleisis has been
      reported and is thought to be related to inadequate lateral drainage channels. To
      date, these cases of postoperative pyometra have been managed using hysterectomy.
      CASE: : We report a case of pyometra after a Le Fort colpocleisis conservatively
      managed with interventional radiologically guided abscess drainage and dilation
      of the lateral drainage tracts. CONCLUSION: Interventional radiology drainage and
      manual dilation of the lateral drainage tracts can be used as an alternative to
      hysterectomy in managing Pyometra after a Le Fort colpocleisis.

PMID- 19155961
TI  - Intracranial subdural hematoma after spinal anesthesia in a parturient.
AB  - BACKGROUND: : An intracranial subdural hematoma is a rare and potentially fatal
      complication of spinal anesthesia. CASE: : A gravida 2, para 1 underwent a repeat
      cesarean for transverse fetal lie. Four hours postoperatively she developed a
      severe headache with acute nausea and vomiting. Computed tomography scan revealed
      a 6-mm right subdural hematoma and midline shift of ventricles. She underwent a
      right frontal craniotomy with evacuation of the hematoma and eventually had a
      complete recovery. CONCLUSION: : Headache and atypical neurologic signs
      presenting after spinal anesthesia should prompt rapid evaluation for
      intracranial hemorrhage.

PMID- 19155962
TI  - Hearing loss in a woman on aspirin: the silent pharmacokinetic parameter.
AB  - A sudden hearing loss in a woman on aspirin has uncovered a frequently neglected
      toxicological parameter.

PMID- 19155963
TI  - Growth hormone in sport: beyond Beijing 2008.
AB  - Human growth hormone (hGH) is a protein endogenously produced predominantly by
      the anterior pituitary gland. Native hGH and, especially, its recombinant
      analogue (rhGH), used to treat patients with hormone deficiency, are supposed to
      be abused by athletes searching its anabolic and lipolytic effects. Hence, hGH
      use has been prohibited for a long time by the sport authorities, but until
      recently, hGH abuse could not be detected. Two approaches have been followed when
      trying to develop methods for GH abuse detection. The direct method identifies an
      abnormal ratio between GH isoforms--a result of hGH exogenous administration. The
      time window to find a cheating athlete by this approach is limited by the
      excretion time of the hormone. The indirect approach measures serum biomarkers
      directly affected by GH intake (eg, markers of released liver growth factors and
      of bone and collagen turnover). In this approach, the retrospective power extends
      further. Alternative possibilities for cheating related to hGH could be the
      administration of recombinant growth factors themselves, the administration of
      hGH metabolic precursors such as ghrelin-like GH secretagogues, or the genetic
      manipulation of muscle growth-related genes (gene doping). In parallel with the
      new types of abuse, which will surely emerge in the near future, the research and
      development for the improvement of the analytical detection of GH itself will
      continue.

PMID- 19155964
TI  - Pharmacokinetics of cyclophosphamide and thiotepa in a conventional fractionated
      high-dose regimen compared with a novel simplified unfractionated regimen.
AB  - High-dose alkylating chemotherapy with cyclophosphamide (4000 or 6000 mg/m2) and
      thiotepa (320 or 480 mg/m2) has commonly been administered in a fractionated
      regimen over 4 days. A simplified unfractionated regimen would be preferable,
      especially because cyclophosphamide and thiotepa have been shown to influence the
      metabolism of each other. However, altering a dose regimen can have a profound
      effect on the pharmacokinetics of the compounds involved. The aim of this study
      was to investigate the effect of altering the fractionated administration
      schedule of the CTC regimen on cyclophosphamide and thiotepa pharmacokinetics.
      Plasma samples were collected from 124 patients who received a fractionated tiny
      CTC or CTC regimen of cyclophosphamide (1000 or 1500 mg m(-2) d(-1)), thiotepa
      (40 or 60 mg/m2 twice daily), and carboplatin (267 or 400 mg m(-2) day(-1)) for 4
      days, and 16 patients who received an unfractionated mini CTC regimen of
      cyclophosphamide (3000 mg/m2 at day 1), carboplatin (400 mg/m2 at days 1 and 2),
      and thiotepa (250 mg/m2 at day 2). Plasma concentrations of cyclophosphamide and
      4-hydroxycyclophosphamide were determined using high-performance liquid
      chromatography coupled with tandem mass spectrometric detection; plasma
      concentrations of thiotepa and tepa were determined using gas chromatography.
      Pharmacokinetics of cyclophosphamide and thiotepa were assessed using nonlinear
      mixed-effect modeling. The study showed that alteration of a fractionated high
      dose regimen into a simplified unfractionated regimen resulted in saturation of
      thiotepa elimination, with a Vmax of 212 (+/-58) micromol/h and a Km of 13.7 (+/
      5.9) microM. This resulted in an increased dose-corrected exposure to thiotepa
      (13%) and decreased dose-corrected exposure to its metabolite tepa (21%).
      Elimination of cyclophosphamide was not shown to be saturable. Dose-corrected
      exposures to cyclophosphamide and its active metabolite 4-hydroxycyclophosphamide
      were comparable in both regimens. Because the simplified unfractionated mini CTC
      regimen was more patient-friendly and because overall dose-corrected exposures to
      cyclophosphamide and thiotepa were not affected to a relevant extent, our data
      suggest that this unfractionated regimen can be used safely in future studies.

PMID- 19155965
TI  - Evaluation of the Cozart DDSV test for cannabis in oral fluid.
AB  - Saliva or "oral fluid" has been presented as an alternative matrix to establish
      drug exposure. The noninvasive collection of an oral fluid sample, which is
      relatively easy to perform and can be achieved under close supervision, is one of
      the most important benefits when testing for driving under the influence of
      drugs. Moreover, the detection of Delta9-tetrahydrocannabinol (THC) in oral fluid
      is a better indication of recent use than a positive urine test, so there is a
      higher probability that the subject is experiencing pharmacological effects at
      the time of sampling. Twenty-five subjects (5 free and 20 addicts from a heroin
      detoxification center) were included in a study to evaluate the potential
      application of a new device, the Cozart DDSV (drug detection system visual), to
      detect cannabis in oral fluid. The time cannabis was last smoked was recorded by
      the medical staff after interview with each subject. Samples were collected with
      the Cozart DDS Oral Swab and diluted with the Cozart DDS buffer as proposed by
      the manufacturer. The Cozart DDSV test was conducted on site at the time of
      collection, and the remainder of the sample retained for confirmation analysis by
      gas chromatography with mass spectrometry (GC/MS) after methylation of THC (limit
      of quantitation 0.5 ng/mL). All 25 samples were analyzed by GC/MS. On-site
      results were obtained within 10 minutes. The 5 drug-free subjects were negative
      for cannabis, irrespective of the method. From the 20 subjects declaring that
      they had smoked cannabis between 30 minutes and 24 hours previously, the DDSV
      device identified 8 positive subjects (with THC concentrations in the buffer in
      the range 15-219 ng/mL), whereas 18 subjects tested positive using GC/MS. THC
      concentrations in the Cozart buffer using GC/MS analysis ranged from 0.7 to 219
      ng/mL. These concentrations represent about one third the authentic THC
      concentrations in oral fluid due to the dilution by the liquid of the device.
      Given the results, the DDSV device was considered as an acceptable tool to detect
      cannabis abuse in oral fluid within a period of 2-3 hours after smoking.

PMID- 19155967
TI  - The role of mTOR inhibitors in the management of posttransplant malignancy.
AB  - Organ transplant recipients given mammalian target of rapamycin inhibitor (mTORi)
      have reduced incidence of de novo posttransplant malignancies (dNPTMs).
      Posttransplant Kaposi's sarcoma and nonmelanotic skin malignancies (NMSC)
      frequently undergo remission/regression after conversion to mTORi
      immunosuppression (IS), especially early, small, and low-grade lesions, whereas
      larger, aggressive, and metastatic skin tumors are less likely to respond. mTORi
      based IS is effective and well tolerated in orthotopic liver transplant patients
      with hepatocellular carcinoma (HCC) achieving excellent survival and disease-free
      intervals, particularly with extended criteria tumors, although the evidence that
      mTORi prevents HCC recurrence after orthotopic liver transplantation is only
      suggestive. Regression of metastatic HCC and other tumors and various forms of
      posttransplant lymphoproliferative disease have occurred after mTOR conversion.
      Documentation of regression/remission of other solid-organ dNPTM (colon, stomach,
      breast, etc.) after mTORi conversion is essentially absent with only anecdotal
      reports lacking follow-up data. Unfortunately, there is not a single reported
      prospective clinical trial powered for looking at the effect of mTORi IS in
      transplant recipients. Nevertheless, reduced incidence of all of dNPTMs and
      remission/regression of the commonest posttransplant tumors with mTOR therapy are
      strong reasons to expand the use of mTORi.

PMID- 19155968
TI  - What does the CONVERT trial really tell us about conversion from calcineurin
      inhibitors to sirolimus?

PMID- 19155969
TI  - ATP measurement predicts porcine islet transplantation outcome in nude mice.
AB  - Current nude mice islet transplantation studies cannot be used prospectively.
      Therefore, to predict transplantation outcomes, reliable and rapid assays for
      islet quality assessment are warranted. This study evaluated the predictive power
      of the porcine islet ATP content on the outcomes of islet transplantation in nude
      mice. Here, we report that the ATP measurement using a small number of handpicked
      islets with a diameter of 100 to 150 mum is a good predictor of islet graft
      efficacy in nude mice. Using receiver-operator characteristic analysis, the area
      under the curve of the ATP content using a small number of handpicked islets was
      0.867 (95% confidence interval 0.744-0.989, P<0.001). The sensitivity and the
      specificity measured were 83.3% and 73.3%, respectively. In conclusion, a simple
      and a rapid measurement of intraislet ATP content could be a promising substitute
      for current nude mice islet transplantation studies.

PMID- 19155970
TI  - Recovery of warm ischemic rat liver grafts by normothermic extracorporeal
      perfusion.
AB  - Liver transplantation is currently the only established treatment of end-stage
      liver disease, but it is limited by a severe shortage of viable donor livers.
      Donors after cardiac death (DCD) are an untapped source that could significantly
      increase the pool of available livers. Preservation of these DCD livers by
      conventional static cold storage (SCS) is associated with an unacceptable risk of
      primary nonfunction and delayed graft failure. Normothermic extracorporeal liver
      perfusion (NELP) has been suggested as an improvement over SCS. Livers recovered
      from male Lewis rats were subjected to 1 hr of warm ischemia and preserved with 5
      hr of SCS or NELP, and transplanted into syngeneic recipients. As additional
      controls, non-ischemic livers preserved with 6 hr of SCS or NELP and unpreserved
      ischemic livers were transplanted. After NELP, ischemically damaged livers could
      be orthotopically transplanted into syngeneic recipients with 92% survival (n=13)
      after 4 weeks, which was comparable with control animals that received healthy
      livers preserved by SCS (n=9) or NELP (n=11) for 6 hr. On the other hand, animals
      from ischemia/SCS control group all died within 12 hr postoperatively (n=6).
      Similarly, animals that received ischemic livers without preservation all died
      within 24 hr after transplantation (n=6). These results suggest that NELP has the
      potential to reclaim warm ischemic livers that would not be transplantable
      otherwise. The rat model in this study is a useful platform to further optimize
      NELP as a method of recovery and preservation of DCD livers.

PMID- 19155971
TI  - Intragraft TNF receptor signaling contributes to activation of innate and
      adaptive immunity in a renal allograft model.
AB  - BACKGROUND: Increased levels of tumor necrosis factor (TNF) are a risk factor for
      allograft rejection. In vitro studies have shown that binding of TNF to its
      receptor activates signaling cascades that induce expression of many genes
      involved in inflammation. The role of intragraft TNF receptor (TNFR) signaling in
      activation of gene expression in allografts has not been studied. METHODS: Gene
      expression profiling and quantitative real-time polymerase chain reaction
      analysis were used to investigate the role of TNFR signaling in the early
      intragraft activation of cellular gene expression in renal allografts at 2 days
      posttransplant. RESULTS: The TNFRs play a critical role in activating intragraft
      expression of transcription factors controlling innate and adaptive immunity and
      stress responses (interferon regulatory factor [IRF]1, IRF 8, Isgf3g, and ATF3)
      of cytokines and receptors mediating inflammation (TNF, interleukin [IL]-6,
      interferon-gamma, oncostatin M receptor [OMCR], toll-like receptor [TLR]2, and IL
      2Rgamma), of chemokines and adhesion molecules that recruit inflammatory cells
      (Cxcl9, Cxcl11, E-selectin, and intracellular adhesion molecule [ICAM]-1), of
      genes involved in costimulation of T cells and processing and presentation of
      antigens (H2-DMb, Psmb8, and CD40), and genes that mediate the response to
      interferons. In addition to its proinflammatory role, TNFR signaling induces
      expression of SOCS3, a negative regulator of IL-6 and OSMR signaling and Nfkbie,
      and a negative regulator of TNFR signal transduction. CONCLUSIONS: These studies
      illustrate the pleiotropic effect of TNF in both activation and down-modulation
      of the immune response and the complex interactions between the TNFRs and other
      cytokine signaling pathways in the early allograft response.

PMID- 19155973
TI  - Upregulating CD4+CD25+FOXP3+ regulatory T cells in pancreatic lymph nodes in
      diabetic NOD mice by adjuvant immunotherapy.
AB  - BACKGROUND: Immunotherapy with Complete Freund's adjuvant (CFA) is effective in
      ameliorating autoimmunity in diabetic nonobese diabetic (NOD) mice. We
      investigated whether CFA treatment up-regulates CD4+CD25+Foxp3+ regulatory T
      cells and increases transforming growth factor (TGF)-beta1 production in diabetic
      NOD mice. METHODS: New-onset diabetic NOD mice were treated with CFA and exendin
      4, a potent analog of glucagon-like peptide-1. Reversal of diabetes was
      determined by monitoring blood glucose level. Ameliorating autoimmunity through
      immunoregulation was assessed by adoptive transfer. Regulatory T cells in the
      peripheral blood, spleen, thymus, and pancreatic nodes were measured. TGF-beta1
      in plasma and the insulin content in the pancreas were also measured.
      Immunostainings for insulin and BrdU were performed. RESULTS: New-onset diabetes
      could be reversed in 38% of NOD mice treated with CFA alone and in 86% of NOD
      mice treated with both CFA and exendin-4. Diabetes adoptive transfer by
      splenocytes from CFA-treated NOD mice was delayed. The percentage of
      CD4+CD25+Foxp3+ regulatory T cells in the pancreatic lymph nodes of CFA-treated
      NOD mice was significantly increased at 1, 5, and 15 to 17 weeks after treatment.
      TGF-beta1 in the plasma of CFA-treated NOD mice was also significantly increased.
      Combining CFA with exendin-4 treatment significantly increased the insulin
      content and the numbers of insulin and BrdU double-labeled beta cells in the
      islets. CONCLUSIONS: Our results demonstrated that CFA treatment ameliorates
      autoimmunity in diabetic NOD mice by up-regulating CD4=CD25+Foxp3+ regulatory T
      cells and increasing TGF-beta1 production. Exendin-4 enhanced the effect of CFA
      on reversing diabetes in NOD mice by stimulating beta-cell replication.

PMID- 19155972
TI  - Development of a humanized mouse model to study the role of macrophages in
      allograft injury.
AB  - BACKGROUND: Nearly half of all infiltrating leukocytes in rejecting human
      allografts are macrophages, yet, in comparison with T cells, much less is known
      about the contribution of this cell type to rejection. Our laboratory has
      previously described models of rejection of human skin or artery grafts in
      immunodeficient mouse hosts mediated by adoptively transferred allogeneic T
      cells. However, mature human monocyte/macrophages have consistently failed to
      engraft in these animals. Here, we describe the introduction of human CD68+
      macrophages into irradiated immunodeficient mice by transplantation of enriched
      CD34+ hematopoietic stem-cells isolated from peripheral blood of G-colony
      stimulating factor pretreated adults. METHODS: We investigated strains of
      immunodeficient mice bearing human tissue grafts (skin and artery) inoculated
      with 1 x 10(6) human CD34+ adult hematopoietic stem cells, peripheral blood
      monuclear cells autologous to the CD34 donor, or both for human cell engraftment.
      RESULTS: In the absence of T cells, CD68+ CD14+ macrophages infiltrate allogeneic
      human skin but produce little injury or thrombosis. Both responses are enhanced
      when combined with adoptive transfer of T cells autologous to the hematopoietic
      stem cells as exemplified by the induction of the macrophage activation marker
      CD163. CD68+ macrophages also infiltrate allogeneic arterial interposition
      grafts, producing intimal expansion and calcification in the absence of T cells.
      CONCLUSIONS: These new models may be used to study the role of human macrophages
      in transplant rejection and other pathologies in vivo.

PMID- 19155974
TI  - Attenuation of transplant arteriosclerosis with clopidogrel is associated with a
      reduction of infiltrating dendritic cells and macrophages in murine aortic
      allografts.
AB  - BACKGROUND: Monotherapy with clopidogrel reduced the formation of transplant
      arteriosclerosis in a murine aortic allograft model. However, the underlying
      immunologic mechanisms are still unknown. METHODS: Fully major histocompatibility
      complex-mismatched C57BL/6 (H2b) donor aortas were transplanted into CBA.J (H2k)
      recipients and mice received different doses (1, 10, and 20 mg/kg) of
      clopidogrel, an antagonist of the P2Y12 ADP receptor on platelets, or control
      saline for 30 days. Blood was analyzed for changes in adhesion molecule and
      sCD40L concentrations by ELISA. Grafts were analyzed by histology, morphometry,
      and immunofluorescence on day 30 after transplantation. Intragraft cytokine mRNA
      production was analyzed by reverse-transcriptase polymerase chain reaction on day
      14 after transplantation. RESULTS: Treatment with clopidogrel resulted in
      significantly decreased blood concentrations of sCD40L and P-selectin after
      transplantation. Cellular analysis of the aortic transplant revealed fewer
      numbers of infiltrating dendritic cells (CD205+) and macrophages (F4/80+) after
      application of clopidogrel, whereas T-cells within the graft were unaltered. In
      addition cellular P-/E-selectin, ICAM-1, and platelet-derived-growth-factor
      (PDGF)-beta surface expression were significantly reduced as compared with
      untreated controls. Intragraft mRNA expression confirmed these results and showed
      significant lower production of P-/E-selectin, ICAM-1, and PDGF-beta after
      treatment with clopidogrel. Antiglycoprotein-Ib and antiglycoprotein VI had no
      beneficial effect on the development of transplant arteriosclerosis. CONCLUSION:
      This report shows that application of clopidogrel after transplantation results
      in a reduction in adhesion molecule expression within the blood and transplant
      tissue and is associated with reduced transendothelial migration of dendritic
      cells and macrophages within the vascular wall.

PMID- 19155975
TI  - Mesenchymal stem cells remain host-derived independent of the source of the stem
      cell graft and conditioning regimen used.
AB  - BACKGROUND: Human bone marrow contains hematopoietic stem cells and stroma cells
      known as mesenchymal stem cells (MSC). MSC are cells with the morphological
      features of fibroblasts, which, in addition to their nursing function for
      hematopoietic stem cells, retain the ability to differentiate into cartilage,
      bone, fat, muscle, and tendon and have an important immunmodulatory function. To
      understand in more detail hematopoietic engraftment and immune modulation after
      hematopoietic cell transplantation, we investigated the ability of donor MSC to
      engraft after hematopoietic cell transplantation in dependency to the
      conditioning regimen (myeloablative vs. reduced intensity) and source of the
      graft (bone marrow vs. peripheral blood). METHODS: Bone marrow MSC of 12 patients
      were analyzed, a median of 23.4 (range 0.9-137.8) months after human leukocyte
      antigen matched but gender mismatched bone marrow transplantation after
      myeloablative conditioning (n=4) or peripheral blood cell transplantation after
      myeloablative (n=4) or reduced intensity conditioning (n=4). MSC were
      characterized by morphology, positivity for CD 105+, CD73+, CD 44+, and CD 90+,
      and by their capacity to differentiate into adipocytic and osteogenic cells.
      Recipient and donor origins were determined by fluorescent in situ hybridization
      for sex chromosomes. RESULTS: While overall blood and bone marrow chimerism was
      100% donor type, MSC remained in all patients of recipient origin (>96%). There
      was no difference between patients receiving bone marrow and peripheral blood
      grafts, nor was any difference observed between patients receiving full intensity
      in comparison with reduced intensity conditioning. CONCLUSIONS: We conclude that
      MSC remain of host type irrespective of the conditioning regimen and graft
      source.

PMID- 19155976
TI  - A pilot study of gene expression-based categorization of pancreas transplant
      biopsies.
AB  - Gene expression profiling has emerged as a powerful strategy to define
      transcriptional mechanism activated in organ transplantation. We performed a
      pilot feasibility study of mRNA-based pancreas transplant biopsy stratification.
      The mRNAs expression of 32 genes, observed in renal transplant dysfunction, and
      10 pancreas-specific genes were evaluated in 26 pancreas transplant biopsy
      specimens by quantitative real-time polymerase chain reaction using TaqMan Low
      Density Array technology. Unsupervised 2D hierarchical clustering segregated the
      biopsies in two main cluster branches, A and B. Six of seven patients (85.7%) in
      cluster A and 6 of 19 (31.6%) in cluster B retained functioning pancreas
      allograft. CD20/MS4A1 mRNA and protein, in addition to CD 3 protein, were
      detected in four specimens in cluster B. Three of those four pancreas transplants
      were subsequently lost. Our study demonstrates the potential association of gene
      expression with clinical outcome of pancreas transplants and justifies further
      studies in an independent cohort.

PMID- 19155977
TI  - Excellent renal allograft survival in donor-specific antibody positive transplant
      patients-role of intravenous immunoglobulin and rabbit antithymocyte globulin.
AB  - BACKGROUND: Timely transplantation of sensitized kidney recipients remains a
      challenge. Patients with a complement-dependent cytotoxicity negative and flow
      cytometry (FC) positive crossmatch carry increased risk of antibody-mediated
      rejection and thus graft loss. Solid phase assays are available to confirm donor
      specificity for antibody identified by FC crossmatch. Treatment using induction
      therapy with rabbit antithymocyte globulin (RATG) and intravenous immunoglobulin
      (IVIG) may allow successful transplant of these high-risk patients. METHODS: A
      retrospective study of 264 consecutive patients after exclusions yielded 94
      complement-dependent cytotoxicity anti-human globulin crossmatch-negative
      patients, including group 1: 58 primary transplants with panel-reactive antibody
      (PRA) less than 20%, group 2: 16 retransplants and PRA more than 20% who were FC
      crossmatch-negative, and group 3: 20 retransplants and PRA more than 20% who were
      FC crossmatch-positive. All were treated with RATG induction and maintenance
      therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. Only group 3
      received IVIG at 500 mg/kg daily in three doses. RESULTS: Eighteen of 20 patients
      in group 3 had donor-specific antibody identified by solid phase assay. Cellular-
      and antibody-mediated rejections were statistically higher in group 3. Two-year
      serum creatinine and glomerular filtration rate along with 3-year patient and
      graft survival were comparable between the groups. CONCLUSIONS: Sensitized
      patients with positive FC crossmatch and donor-specific antibody identified by
      solid phase assays can be successfully transplanted using standard RATG
      induction, IVIG, and maintenance immunosuppression with equal renal function and
      graft survival to immunologically lower risk recipients. Given these results,
      this patient group should not be excluded from transplantation based on antibody
      specificities determined by virtual crossmatch techniques.

PMID- 19155979
TI  - Life-years gained by reducing donor heart ischemic times.
AB  - BACKGROUND: Transplantation is limited by the number of available donor organs.
      Donor organ maintenance systems are a recent technological advance. These systems
      may increase the number of donor organs that can be used and improve outcomes by
      decreasing donor organ ischemic time (IT). The purpose of this study was to
      determine the potential life-years gained if IT in the United Kingdom were
      decreased for cardiac transplantation. METHODS: Proportional hazards regression
      and extrapolation of survival rates beyond 20 years posttransplantation were used
      to estimate the effect of decreasing total IT on survival and the life-years
      gained over the lifetime of UK heart transplantation patients. RESULTS: Median
      survival posttransplantation was 10.4 years (95% CI 9.9 to 10.9). For each
      additional hour of donor organ IT, patients had a 25% increased risk of death
      after heart transplantation in the first year after transplant, with a 5%
      increase thereafter (P<0.001). On average, a recipient surviving 10 years
      posttransplantation could potentially gain 0.4 (95% CI 0.1 to 0.7) life-years if
      IT was reduced to 1 hr. The longer the IT, the greater the potential life-years
      to gain; for example, a recipient of an organ that would have had an IT of 6 hr
      without the use of an organ maintenance system might expect to gain 2.9 life
      years (95% CI -0.6 to 6.4) if IT was reduced to 1 hr. CONCLUSIONS: Use of cardiac
      donor organ maintenance systems has the potential to increase posttransplantation
      survival.

PMID- 19155980
TI  - Predictive role of pretransplant serum CXCL10 for cardiac acute rejection.
AB  - BACKGROUND: The detection of acute rejection in heart transplantation remains an
      important feature of transplant management, especially in the early phase.
      Frequent surveillance with endomyocardial biopsy is necessary, even though it is
      an invasive procedure and carries a certain risk. Hence, noninvasive biomarkers
      able to predict acute rejection could be a further helpful tool in patient
      management. The interferon-gamma-inducible chemokine CXCL10 is required for
      initiation and development of graft failure caused by acute or chronic rejection.
      It has been reported that CXCL10 serum level is predictive of graft loss in
      kidney graft recipients. In the present study, we investigated whether
      pretransplant CXCL10 serum level may be a predictive noninvasive biomarker in
      heart transplant (HTx) recipients, as well. METHODS: Sera from 143 patients
      undergoing orthotopic heart transplantation were collected before surgery and
      tested for CXCL10 and CCL22 and compared with serum samples from healthy
      subjects. RESULTS: We found that basal CXCL10 serum levels in HTx recipients were
      significantly higher than in healthy subjects, whereas no difference was seen in
      CCL22 levels. Among HTx recipients, CXCL10 serum levels of rejectors were
      significantly higher than in nonrejectors. Our results showed that CXCL10 was a
      significant independent risk factor of several variables and had the highest
      predictive value for early acute heart rejection, with 160 pg/mL cutoff value.
      CONCLUSIONS: In HTx recipients, measurement of pretransplant CXCL10 serum levels
      could be a clinically useful tool for predicting cardiac acute rejection,
      especially in the early posttransplant period.

PMID- 19155981
TI  - False-positive results of Aspergillus galactomannan antigenemia in liver
      transplant recipients.
AB  - BACKGROUND: Aspergillus galactomannan (GM) antigenemia is an early marker of
      invasive aspergillosis (IA), but may yield false-positive results. A prospective
      study, testing GM periodically in serum samples of liver transplant recipients,
      was performed. METHODS: An index more than or equal to 0.5 were considered
      positive. Positive GM in samples from patients without any other criteria of
      proven or probable IA was considered as false-positive. The test was performed
      weekly during the first month after transplantation. RESULTS: Three patients
      developed IA. In total, 414 serum samples from 85 liver transplant recipients
      were analyzed. Mean number of samples per patient (out of those who could be
      assessed) was 4.8. The number of false-positive GM samples was 40 (9.6%),
      corresponding to 28 patients. The frequency of false-positive results in samples
      obtained during the first week posttransplantation was 36% (27 of 75),
      significantly higher than the number of false-positive samples obtained after the
      first week (3.8%; 13 of 339; P<0.001). Multivariate analysis showed that
      antibacterial prophylaxis with ampicillin was the only independent factor
      associated with a false-positive result. Different vials of beta-lactam
      antibiotics were tested for GM. We obtained a positive GM value (>0.5) in four of
      the six vials of ampicillin, in three of the six vials of piperacillin
      tazobactam, in none of the six vials of cefotaxime, and in none of the six
      controls. CONCLUSIONS: The present study suggests that the administration of
      ampicillin as antibacterial prophylaxis during the first days after
      transplantation could be a possible cause of false-positive GM results.

PMID- 19155978
TI  - Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal
      allograft recipients: 24-month efficacy and safety results from the CONVERT
      trial.
AB  - BACKGROUND: The efficacy and safety of converting maintenance renal transplant
      recipients from calcineurin inhibitors (CNIs) to sirolimus (SRL) was evaluated.
      METHODS: Eight hundred thirty renal allograft recipients, 6 to 120 months
      posttransplant and receiving cyclosporine or tacrolimus, were randomly assigned
      to continue CNI (n=275) or convert from CNI to SRL (n=555). Primary endpoints
      were calculated Nankivell glomerular filtration rate (GFR; stratified at
      baseline: 20-40 vs. >40 mL/min) and the cumulative rates of biopsy-confirmed
      acute rejection (BCAR), graft loss, or death at 12 months. Enrollment in the 20
      to 40 mL/min stratum was halted prematurely because of a higher incidence of
      safety endpoints in the SRL conversion arm. RESULTS: Intent-to-treat analyses at
      12 and 24 months showed no significant treatment difference in GFR in the
      baseline GFR more than 40 mL/min stratum. On-therapy analysis of this cohort
      showed significantly higher GFR at 12 and 24 months after SRL conversion. Rates
      of BCAR, graft survival, and patient survival were similar between groups. Median
      urinary protein-to-creatinine ratios (UPr/Cr) were similar at baseline but
      increased significantly after SRL conversion. Malignancy rates were significantly
      lower at 12 and 24 months after SRL conversion. Post hoc analyses identified a
      subgroup with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to
      0.11, whose risk-benefit profile was more favorable after conversion than that
      for the overall SRL conversion cohort. CONCLUSIONS: At 2 years, SRL conversion
      among patients with baseline GFR more than 40 mL/min was associated with
      excellent patient and graft survival, no difference in BCAR, increased urinary
      protein excretion, and a lower incidence of malignancy compared with CNI
      continuation. Superior renal function was observed among patients who remained on
      SRL through 12 to 24 months, particularly in the subgroup of patients with
      baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11.

PMID- 19155982
TI  - Long-term outcomes for 32 cases of Wilson's disease after living-donor liver
      transplantation.
AB  - BACKGROUND: Long-term outcomes after living donor liver transplantation (LDLT) in
      Wilson's disease (WD) with heterozygous donors for WD gene are unknown. METHODS:
      LDLT was performed for 32 patients with WD (15 men, 17 women; mean age 16 years;
      range, 6-40 years) at Kyoto University Hospital from 1992 to 2006. The mean
      follow-up time from LDLT was 6.7+/-4.0 years (0.04-15.0 years). Donors were
      mainly parents (90.6%), who were obligatory carriers of the WD mutation. The
      present study examined retrospectively the copper metabolism, recurrence of WD,
      survival rate, and neurologic outcomes after LDLT. RESULTS: Mean ceruloplasmin at
      the time of LDLT was 9.7+/-7.3 mg/dL and increased to 22.3+/-5.3 mg/dL (normal,
      18-37 mg/dL). Urinary copper decreased from 2704+/-901 to 73.7+/-5.2 microg/day
      (normal, <50 microg/day). Serum copper improved from 72.9+/-33.9 to 81.0+/-14.9
      mg/dL (normal, 78-131 mg/dL). Although six patients died and two received
      retransplantation, the remaining 24 remain alive without recurrence, with overall
      survival rates of 90.6%, 83.7%, and 79.9% at 1, 5, and 10 years, respectively.
      Patients with chronic liver failure had a poorer prognosis (P<0.05). CONCLUSION:
      Use of liver grafts from heterozygous donors has been considered safe. Good
      improvements in copper metabolism were obtained without evidence of recurrence in
      long-term follow-up. Neuropsychologic presentations of WD improved or remained
      unchanged. Indications for liver transplantation in patients with WD with
      neurologic symptoms must be considered carefully based on the stage of neurologic
      damage and its irreversibility.

PMID- 19155983
TI  - Living donor kidney transplantation across positive crossmatch: the University of
      Illinois at Chicago experience.
AB  - BACKGROUND: To increase living donation for kidney transplantation, we
      investigated desensitization of recipients with positive crossmatch against a
      potential living donor. METHODS: Between June 2001 and March 2007, 57 consecutive
      sensitized candidates for kidney transplantation, with crossmatch positive
      potential living donors, were treated with various desensitization protocols. All
      patients received plasmapheresis every other day with intravenous immune globulin
      100 mg/kg starting 1 week before the scheduled transplant. Postoperatively, the
      recipients continued to receive every other day plasmapheresis with intravenous
      immune globulin for the initial week. Immunosuppression therapy consisted of
      induction with thymoglobulin and a combination of tacrolimus, mycophenolate, and
      corticosteroids. RESULTS: Six patients failed to convert with pretransplant
      immunomodulation and were not transplanted; 51 underwent live donor kidney
      transplant. Mean follow-up was 23 months and 36 patients have more than 1-year
      follow-up. One-year patient and graft survivals were 95% and 93%, respectively.
      There were 25 episodes of biopsy-proven or clinically presumed rejection in 22
      patients in the first year. Of the 17 biopsy-proven episodes, 12 were antibody
      mediated rejection and five were acute cellular rejection. Of the patients with
      antibody-mediated rejection (biopsy proven or empiric), two patients (12%) lost
      their graft by 1 year. The median modification of diet in renal disease at 6 and
      12 months was 55 mL/min (range 9-104 mL/min) and 48 mL/min (range 8-99),
      respectively. CONCLUSIONS: Despite increased rejection rates, graft and patient
      survivals indicate that desensitization of positive crossmatch patients is a
      reasonable alternative for a sensitized patient who could potentially wait 10 or
      more years for a suitable cadaveric kidney.

PMID- 19155984
TI  - Hyperinsulinemia and hyperfiltration in renal transplantation.
AB  - BACKGROUND: Insulin-resistance hyperinsulinemia is a novel risk factor for renal
      disease in the general population. Glomerular hyperfiltration has been proposed
      as an early consequence of hyperinsulinemia. METHODS: In this multicenter cohort
      study, we analyzed 202 patients without diabetes before or after renal
      transplantation during the first posttransplant year. Insulin was measured at 3
      and 12 months. The majority of patients (91%) were on calcineurin inhibitors.
      Patients were classified as with persistent normo or hyperinsulinemia when
      situated below or above the median value of insulin (3 months: 9 muU/mL; 12
      months: 8.74 muU/mL) at both periods. The 3 to 12 months percent change in
      calculated creatinine clearance (3-12 months DeltaCrCL) was calculated. RESULTS:
      Patients with persistent hyperinsulinemia showed a higher increase in 3 to 12
      months DeltaCrCL compared with those with persistent normoinsulinemia (12% [
      20/40] vs. -0.03% [-12/18], P=0.035). We performed a multivariate linear
      regression analysis with the 3 to 12 months DeltaCrCL as the dependent variable
      and different factors that may induce hyperfiltration, including persistent
      hyperinsulinemia, as covariates. Persistent hyperinsulinemia was a risk factor
      for increased CrCL (beta 0.09, 95% CI 0.07/0.12, P=0.035). CONCLUSION: In
      nondiabetic recipients during the first posttransplant year, hyperinsulinemia
      induced increments in CrCL. As this may herald future renal dysfunction,
      hyperinsulinemia should not be ignored as a potential target in this population.

PMID- 19155985
TI  - Kidney transplant outcomes in patients with Fabry disease.
AB  - BACKGROUND: Fabry disease is a rare but important cause of end-stage renal
      disease (ESRD) among young men. Postkidney transplantation outcomes among
      patients with Fabry disease remain controversial. METHODS: Using data from Organ
      Procurement Transplant Network/United Network for Organ Sharing, 197 kidney
      transplant recipients with ESRD because of Fabry disease from 1987 to 2007 were
      identified. We compared rates of graft loss and death with those of kidney
      transplant recipients with other (non-Fabry) causes of ESRD. Fabry patients were
      then compared with a 10:1 matched cohort of transplant recipients with other
      causes of ESRD. RESULTS: Five-year graft survival was superior among Fabry
      patients (74%) compared with those with other causes of ESRD (69%), but was
      similar to those in the matched cohort (P=0.64). Five-year patient survival among
      Fabry patients (81%) was similar to those with other causes of ESRD (P=0.33), but
      was inferior to the matched cohort (90%). Cox multivariate analysis revealed that
      Fabry patients had a 40% lower risk of returning to dialysis compared with both
      matched and unmatched cohorts, but had a higher risk of death (2.15; 1.52-3.02)
      compared with the matched cohort. CONCLUSION: This analysis of 197 kidney
      transplant recipients with Fabry indicates that they have superior graft survival
      and similar patient survival compared with patients with other causes of ESRD.
      However, Fabry patients had a higher risk of death compared with a matched cohort
      of patients with other causes of ESRD. This requires further investigation and
      may suggest a need for further attention to the minimization of cardiovascular
      death in this group of patients.

PMID- 19155986
TI  - A single low-fixed dose of rituximab to salvage renal transplants from refractory
      antibody-mediated rejection.
AB  - Rituximab may improve graft survival in renal acute antibody-mediated rejection
      (AMR), but data confirming efficacy and optimal dosing is lacking. High-dose
      regimens may be associated with significant rates of infective complications. We
      therefore conducted a pilot study of a single low-fixed dose (500 mg) of
      rituximab in seven consecutive patients with AMR resistant to standard therapy.
      After a mean follow-up of 21 months (range, 9.5-33 months), graft and patient
      survival were 100% with serum creatinine levels significantly lower than peak
      rejection levels (171+/-73 micromol/L vs. 559+/-358 micromol/L, P=0.028). B cells
      were undetectable in all patients for more than or equal to 6 months and in six
      of seven patients for more than or equal to 12 months after rituximab. Three
      patients encountered a significant infective complication including
      cytomegalovirus reactivation, viral pneumonia, and polyoma viral nephropathy. All
      have since resolved. A single low-fixed dose of rituximab may help improve graft
      survival in AMR and offers the potential advantage of reduced infective
      complications.

PMID- 19155987
TI  - Histogenomics: association of gene expression patterns with histological
      parameters in kidney biopsies.
AB  - BACKGROUND: Several studies investigated the association of histologic scores of
      donor kidney biopsies obtained before engraftment with posttransplant outcomes.
      Discrimination and goodness of fit of these scores, however, is low. METHODS:
      Thus, we sought to identify and elucidate the performance of molecular rather
      than histologic markers for this purpose using whole genome gene expression
      microarray experiments. RESULTS: We identified 80 unique differentially regulated
      genes in 82 samples, showing no histologic damage versus those with histologic
      damage, based on the Chronic Allograft Damage Index (CADI) and acute tubular
      injury. Main biological categories enriched with up-regulated genes in damaged
      tissue were "immunity and defense," "cell communication," or "apoptosis."
      Interestingly, genes involved in cell structure, cell adhesion, and protein
      trafficking were specific for tubular atrophy. Histology (CADI score) explained
      only 14% of the variability of 1 year creatinine (adjusted R2 for panel-reactive
      antibodies, biopsy confirmed acute rejection, and sum of human leukocyte antigen
      mismatches) whereas a combination of three biomarkers without clinical
      covariables explained 28%. The three molecular markers are the NLR family, pyrin
      domain containing 2 (NLRP2), immunoglobulin J polypeptide, and the regulator of G
      protein signaling 5. CONCLUSION: In summary, we identified biomarkers in
      transplant kidney biopsies, which are predictive for medium-term allograft
      function.

PMID- 19155988
TI  - A systematic approach to minimizing wound problems for de novo sirolimus-treated
      kidney transplant recipients.
AB  - BACKGROUND: Wound healing problems and lymphoceles have been reported with
      greater frequency in kidney recipients given de novo sirolimus. This problem has
      led to increased patient morbidity and cost; and has been an impediment to the
      completion of randomized controlled trials in which wound problems have
      necessitated premature discontinuation of mammalian target of rapamycin
      inhibitors. METHODS: We developed a systematic program to reduce these problems
      based on patient selection (body mass index [BMI] <32 kg/m2), the use of closed
      suction drains, modifications of surgical technique, and avoidance of a loading
      dose of sirolimus. Consecutive series of adult kidney-only recipients given
      antibody induction followed by de novo sirolimus, mycophenolate mofetil, and
      steroids were compared; group 1: 204 patients transplanted with few restrictions
      and group 2: 103 patients transplanted using the above program. RESULTS: This
      approach resulted in a significant reduction (group 2 vs. group 1) in cumulative
      wound complications (7.8% vs. 19.6%, P=0.007), and nonoperative wound
      complications (2.9% vs. 14.2%, P=0.001). In addition, the incidence of
      lymphoceles detected (22.3% vs. 47.1%, P<0.0001), treated (4.8% vs. 24.5%,
      P<0.0001), or needing surgical intervention (1.9% vs. 14.2%, P=0.001) was
      significantly reduced. Multivariate analysis demonstrated that a BMI more than 30
      to 32 kg/m2 was the most significant variable related to delayed wound healing
      (odds ratio [OR] 3.01, 0.02) or surgical repair (OR 8.05, P=0.0001), whereas BMI
      (OR 1.54, P=0.038) and acute rejections (OR 1.34, P=0.03) were most associated
      with lymphocele treatment. CONCLUSIONS: A systematic program of wound care using
      de novo sirolimus can produce wound healing complications comparable with that
      reported with other agents.

PMID- 19155989
TI  - A Page kidney case report with diastolic flow reversion in Doppler
      ultrasonography.

PMID- 19155990
TI  - Living donor liver transplantation with vena cava reconstruction using a
      cryopreserved allograft for a pediatric patient with Budd-Chiari syndrome.

PMID- 19155991
TI  - Prophylaxis versus preemptive therapy for prevention of the consequences of
      cytomegalovirus infection in transplant recipients: a still unresolved issue.

PMID- 19155994
TI  - Estimation of HIV incidence in San Francisco.
AB  - The Centers for Disease Control and Prevention recently released the first direct
      national estimate of HIV incidence. Local jurisdictions have begun to apply this
      methodology. The national and local estimates have been higher than assumed. When
      applied to San Francisco, there were 935 new HIV infections [95% confidence
      interval (CI) 658-1212] during 2006. We compared this incidence estimate to an
      estimate produced in San Francisco in 2006 by a panel of HIV researchers using an
      iterative Delphi method. Results were similar. Further corroboration of the new
      method in local areas would strengthen interpretation and identify HIV risk
      variations.

PMID- 19155993
TI  - Impact of aciclovir on genital and plasma HIV-1 RNA in HSV-2/HIV-1 co-infected
      women: a randomized placebo-controlled trial in South Africa.
AB  - BACKGROUND: Several studies suggest that herpes simplex virus type 2 (HSV-2) may
      enhance HIV-1 transmission and disease progression. METHODS: We conducted a
      randomized, double-blind, placebo-controlled trial of aciclovir 400 mg twice
      daily for 3 months in 300 HSV-2/HIV-1 co-infected women not yet on highly active
      antiretroviral therapy (HAART). Participants were evaluated prerandomization and
      at monthly visits for 3 months. Primary outcomes were the detection and quantity
      of genital HIV-1 RNA at the month 3 (M3) visit. Analyses were also undertaken
      using data from all visits. The treatment effects on plasma HIV-1 RNA, CD4 cell
      count and genital HSV-2 DNA were also assessed. RESULTS: At M3 fewer women had
      detectable genital HIV in the aciclovir group compared to placebo, but this was
      not significant [61/132 (46%) vs. 71/137 (52%), risk ratio (RR) 0.89, 95%
      confidence interval (CI) 0.70-1.14; P = 0.36]. There was also little difference
      in quantity of HIV-1 RNA among shedders (+0.13 log10 copies/ml, 95% CI -0.14 to
      0.39) at M3. However, aciclovir significantly decreased the frequency of HIV-1
      shedding over all visits [adjusted odds ratio (OR) 0.57, 95% CI 0.36-0.89].
      Significant reductions in M3 plasma HIV-1 RNA (-0.34 log10 copies/ml, 95% CI 0.15
      0.54), genital HSV-2 DNA (8 vs. 20%, RR 0.37, 95% CI 0.19-0.73) and genital
      ulceration (8 vs. 18%, RR 0.43, 95% CI 0.22-0.84) were observed in the aciclovir
      group. CONCLUSION: HSV-2 suppressive therapy, by reducing HIV-1 plasma viral load
      and altering the pattern of genital HIV-1 shedding, may contribute to the
      reduction in sexual transmission of HIV-1 and may delay the requirement for HAART
      initiation.

PMID- 19155995
TI  - On the origin of South America HIV-1 C epidemic.

PMID- 19155996
TI  - Prognostic significance of C-reactive protein and smoking in patients with
      advanced non-small cell lung cancer treated with first-line palliative
      chemotherapy.
AB  - HYPOTHESIS: The objective of the study was to analyze if C-reactive protein (CRP)
      and smoking status provide prognostic information in patients with advanced non
      small cell lung cancer (NSCLC) receiving palliative first-line chemotherapy.
      METHODS: Retrospective, single-institutional study, comprising all patients with
      NSCLC stage IIIB/IV and World Health Organization performance status (PS) 0-2 who
      started palliative first-line chemotherapy between January 1, 2002, and January
      31, 2007. Patient records were reviewed. Cox's proportional hazards model was
      used to identify prognostic factors. RESULTS: Two hundred eight-nine consecutive
      patients were evaluable. Sixty-eight percent had stage IV disease and 67% had PS
      0 or 1. Median survival was 7.4 months. At onset of chemotherapy, 206 patients
      (71%) had elevated CRP values (> or = 10 mg/liter). One-hundred-forty-four
      patients (50%) were current smokers. On univariate analysis, patients with
      elevated CRP levels had inferior survival (hazard ratio [HR] = 1.67, 95%
      confidence interval [CI], 1.28-2.19, p < 0.001). Smoking at onset of treatment
      was associated with shorter survival (HR 1.56, 95% CI, 1.22-1.98, p < 0.001).
      Ever smokers had shorter survival than never smokers (HR 1.80, 95% CI, 1.25-2.59,
      p = 0.001). On multivariate analysis, with stage, PS, albumin, and gender as
      covariates, both smoking at start of chemotherapy and CRP elevation were
      independent negative prognostic factors for survival. CONCLUSIONS: CRP and
      smoking status are independent prognostic factors for survival in patients with
      advanced NSCLC receiving palliative first-line chemotherapy and provide
      additional information to established prognostic factors such as stage of disease
      and performance status.

PMID- 19155997
TI  - Tryptase mast cells in malignant pleural mesothelioma as an independent favorable
      prognostic factor.
AB  - INTRODUCTION: Malignant pleural mesothelioma is a highly aggressive neoplasm with
      an incidence that is increasing world-wide. Mast cells are part of the innate
      immune system and have been associated with different solid tumors, but there is
      controversy surrounding their pro- and antitumorigenic effects in cancers. There
      are two subsets of human mast cells, resulting from the expression of different
      enzymes: tryptase positive mast cells and chymase positive mast cells. The
      purpose of this study was to determine the presence and prognostic significance
      of tumor infiltrating mast cells in mesothelioma. METHODS: Tryptase and chymase
      mast cell counts were determined by immunohistochemistry in 60 patients with
      mesothelioma. All pathologic samples were from patients who underwent treatment
      with intrapleural preoperative interleukin-2 (18 x 10(6) IU/d for 3 days). After
      one day of recovery, patients underwent surgery. Pleural samples were also
      immunostained for CD34 to evaluate microvessel count. RESULTS: High tryptase mast
      cells counts were found in the majority (73.3%) of the cases studied, and the
      results were significantly associated with both overall survival (p = 0.02) and
      time to progression (p = 0.01). This finding was confirmed using multivariate
      analysis: a higher tryptase mast cells count emerged as an independent favorable
      prognostic factor (p = 0.02). However, tryptase mast cells count did not show
      significant correlation with microvessel count. CONCLUSIONS: These results
      suggest that tumor infiltrating tryptase mast cells, after interleukin-2
      preoperative induction therapy, predict improved clinical outcome in patients
      with malignant pleural mesothelioma, and highlight the critical role of the local
      inflammatory response in mesothelioma cancer progression.

PMID- 19155998
TI  - Phase II study of docetaxel and carboplatin in elderly patients with advanced non
      small cell lung cancer.
AB  - BACKGROUND: Mainly single-agent chemotherapy has been considered as standard
      treatment for elderly patients with non-small cell lung cancer (NSCLC). Docetaxel
      monotherapy is regarded as a standard treatment for elderly patients with
      advanced NSCLC, and recent subset analyses have suggested that platinum-based
      chemotherapy can be safely used in the elderly. This phase II study was conducted
      to evaluate the efficacy and safety of docetaxel and carboplatin in elderly
      patients with advanced NSCLC. METHODS: Patients enrolled in this study had stage
      IIIB or IV NSCLC with measurable disease, no prior chemotherapy, Eastern
      Cooperative Oncology Group performance status of 0-2, and were 70 years or older.
      Treatment consisted of docetaxel at a dose of 60 mg/m(2) and carboplatin at area
      under the curve of 5 mg/ml/min on day 1 every 3 weeks. RESULTS: From October 2003
      to April 2006, 30 patients were enrolled. One complete response and 13 partial
      responses were observed, for an overall response rate of 46.7% (95% confidence
      interval: 28.8-64.6%). Median progression-free survival and overall survival
      periods were 4.4 months and 9.9 months, respectively. One-year survival rate was
      43.3%. Major grade 3 and 4 hematological toxicities included neutropenia (86.7%),
      leucopenia (80.0%) and febrile neutropenia (16.7%). Major grade 3
      nonhematological toxicities were anorexia (30.0%) and diarrhea (13.3%). There
      were no grade 4 nonhematological toxicities or treatment-related deaths.
      CONCLUSIONS: Docetaxel combined with carboplatin was an active treatment with
      manageable toxicity for the treatment of elderly patients with chemotherapy-naive
      NSCLC.

PMID- 19155999
TI  - A randomized phase II trial assessing in advanced non-small cell lung cancer
      patients with stable disease after two courses of cisplatin-gemcitabine an early
      modification of chemotherapy doublet with paclitaxel-gemcitabine versus
      continuation of cisplatin-gemcitabine chemotherapy (GFPC 03-01 Study).
AB  - BACKGROUND: There is no consensus on the optimal treatment for patients with
      advanced non-small cell lung cancer and stable disease after cisplatin-based
      chemotherapy. The objective of the trial was to evaluate a switch to a different
      dual-agent chemotherapy. METHODS: Patients with stage IV non-small cell lung
      cancer and stable disease after two cycles of cisplatin (P) and gemcitabine (G)
      (P day1 (d(1)): 75 mg/m(2), G: 1250 mg/m(2) d(1) and d(8) every 3 weeks) were
      randomized to receive either two further cycles of PG (arm A) or paclitaxel (100
      mg/m(2) d(1), d(8), d(15)) plus gemcitabine (1250 mg/m(2) d(1) and d(8), every 4
      weeks) (arm B). RESULTS: Two-hundred-twenty-eight patients were enrolled between
      October 2003 and August 2006. After two cycles of PG, 98 patients (43%) had
      stable disease; 87 were randomized: 45 to arm A and 42 to arm B. The objective
      response rates were 15.6% (6.5-29.4) and 21.4% (10.3-36.8) in arms A and B.
      Overall survival after randomization was 9.6 months (7.0-13.8) in arm A and 9.3
      months (7.4-13.3) in arm B. Adverse events were similar in the two arms for
      hematological and non hematological toxicities. CONCLUSIONS: Sequential first
      line chemotherapy in these patients is feasible with no difference in response
      rates. These results do not warrant a phase III trial.

PMID- 19156000
TI  - Multi-modality mediastinal staging for lung cancer among medicare beneficiaries.
AB  - INTRODUCTION: The use of noninvasive and invasive diagnostic tests improves the
      accuracy of mediastinal staging for lung cancer. It is unknown how frequently
      multimodality mediastinal staging is used, or whether its use is associated with
      better health outcomes. METHODS: A cohort study was conducted using Surveillance,
      Epidemiology, and End Results-Medicare data (1998-2005). Patients were
      categorized as having undergone single (computed tomography [CT] only), bi- (CT
      and positron emission tomography or CT and invasive staging), or tri-modality
      (CT, positron emission tomography, and invasive staging) staging. RESULTS: Among
      43,912 subjects, 77%, 21%, and 2% received single, bi-, and tri-modality staging,
      respectively. The use of single modality staging decreased over time from 90% in
      1998 to 67% in 2002 (p-trend <0.001), whereas the use of bi- and tri-modality
      staging increased from 10% to 30% and 0.4% to 5%, respectively. After adjustment
      for differences in patient characteristics, the use of a greater number of
      staging modalities was associated with a lower risk of death (bi- versus single
      modality: hazard ratio [HR] 0.58, 99% confidence interval [CI] 0.56-0.60; tri-
      versus single modality: HR 0.49, 99% CI 0.45-0.54; tri- versus bi-modality: HR
      0.85, 99% CI 0.77-0.93). These associations were maintained even after excluding
      stage IV patients or adjustment for stage. CONCLUSIONS: The use of multimodality
      mediastinal staging increased over time and was associated with better survival.
      Stage migration and unmeasured patient and provider characteristics may have
      affected the magnitude of these associations. Cancer treatment guidelines should
      emphasize the potential relationship between staging procedures and outcomes, and
      health care policy should encourage adherence to staging guidelines.

PMID- 19156001
TI  - The applicability of the proposed IASLC staging revisions to small cell lung
      cancer (SCLC) with comparison to the current UICC 6th TNM Edition.
AB  - BACKGROUND: We examined the impact of the proposed Internal Association for the
      Study of Lung Cancer (IASLC) tumor, node, metastasis (TNM) and stage grouping
      revisions on staging and survival outcome of small cell lung cancer (SCLC).
      METHODS: A total of 10,660 SCLC patients from the California Cancer Registry
      between 1991 to 2005 with complete TNM staging were identified and reclassified
      according to the IASLC proposed TNM revisions and new stage groupings.
      Surveillance Epidemiology and End Results extent of disease codes were used to
      identify various T4 and M descriptors. Cox proportional hazards regression was
      used to identify prognostic factors. RESULTS: Survival was correlated with the
      current UICC6 and IASLC proposed T descriptors. Patients without mediastinal
      lymph node involvement (N 0-1) had superior survival compared to patients with
      mediastinal lymph node involvement (N 2-3). The IASLC proposed stage grouping
      results in better separation of survival curves among early stage SCLC than the
      current Union Internationale Centre le Cancer (UICC) 6 stage groupings by both
      univariate and multivariate analyses. Pleural effusion (IASLC M1a) in SCLC had
      survival similar to other IASLC M1a categories (pericardial effusion,
      contralateral intrapulmonary metastasis) by pairwise hazard ratio comparisons.
      CONCLUSIONS: The IASLC proposed TNM staging changes result in better separation
      of stage-specific SCLC survival curves than the current UICC6 staging system. The
      new IASLC M1a descriptors (pleural effusion, pericardial effusion, and
      contralateral/bilateral intrapulmonary metastasis) adequately prognosticate SCLC
      patients as having metastatic disease.

PMID- 19156004
TI  - Myopia: the gauntlet is thrown down.

PMID- 19156003
TI  - Has near work's star fallen?

PMID- 19156006
TI  - Barry Collin: a visionary for a new direction in optometry.
AB  - Dr. Barry Collin represents the best in academic optometry. An educator,
      scientist, and visionary, he has throughout his long and distinguished career
      made important contributions to our understanding of ophthalmic pathology. He has
      also had an enormous impact on raising the level of optometric education and
      expanding the scope of optometric practice. This profile covers much of Dr.
      Collin's professional career, offering insights into what has made him one of the
      key leaders in Australian and international optometry.

PMID- 19156007
TI  - Can clinicians use the PHQ-9 to assess depression in people with vision loss?
AB  - PURPOSE: To investigate whether the Patient Health Questionnaire-9 (PHQ-9)
      possesses the essential psychometric characteristics to measure depressive
      symptoms in people with visual impairment. METHODS: The PHQ-9 scale was completed
      by 103 participants with low vision. These data were then assessed for fit to the
      Rasch model. RESULTS: The participants' mean +/- standard deviation (SD) age was
      74.7 +/- 12.2 years. Almost one half of them (n = 46; 44.7%) were considered to
      have severe vision impairment (presenting visual acuity <6/60 in the better eye).
      Disordered thresholds were evident initially. Collapsing the two middle
      categories produced ordered thresholds and fit to the Rasch model (chi = 10.1;
      degrees of freedom = 9; p = 0.34). The mean (SD) items and persons Fit Residual
      values were -0.31 (1.12) and -0.25 (0.78), respectively, where optimal fit of
      data to the Rasch model would have a mean = 0 and SD = 1. Unidimensionality was
      demonstrated confirming the construct validity of the PHQ-9 and there was no
      evidence of differential item functioning on a number of factors including visual
      disability. The person separation reliability value was 0.80 indicating that the
      PHQ-9 has satisfactory precision. There was a degree of mistargeting as expected
      in this largely non-clinically depressed sample. CONCLUSIONS: Our findings
      demonstrate that the PHQ-9, when scaled with Rasch analysis, forms a linear
      interval measurement of depressive symptoms suitable for use in a vision impaired
      population.

PMID- 19156008
TI  - The Samisch case and the Mullers of Wiesbaden.
AB  - PURPOSE: There are significant inconsistencies in accounts in textbooks of the
      fitting in 1887 of a device resembling a scleral contact lens. The aim of this
      study was to establish the facts of this case and to provide an overview of the
      subsequent clinical performance of blown scleral shells and lenses. METHODS: A
      literature search was conducted that included the original report published in
      1910 of the fitting of the patient. The dimensions and back vertex power of a
      blown scleral shell were measured. RESULTS: In 1887, the right eye of a patient
      with lagophthalmic keratitis as a sequel to cancerous destruction of the lower
      eyelid was fitted with a protective blown scleral shell. His left eye was
      effectively blind. The referring ophthalmologist was Professor Theodor Samisch of
      Bonn and the fitting was undertaken by the firm of F Ad Muller & Sohne of
      Wiesbaden, Germany. With periodical replacement, a shell was worn for at least 21
      years. Muller scleral shells were principally fitted in keratoconus providing
      markedly improved visual acuities and wearing times of up to 14 h a day. There
      were instances of continuous wear. CONCLUSIONS: Failure to consult original
      sources is responsible for errors in descriptions of the Samisch case that is of
      historical importance because it represents both the first use of a therapeutic
      contact shell and the first instance of continuous wear. Blown scleral shells and
      lenses played an important part in the optical correction of keratoconus and the
      management of other ocular conditions during the first quarter of the 20th
      century.

PMID- 19156009
TI  - Visual comparison of multifocal contact lens to monovision.
AB  - PURPOSE: To compare visual function with the Bausch & Lomb PureVision multifocal
      contact lens to monovision with PureVision single vision contact lenses. METHODS:
      Twenty presbyopic subjects were fitted with either the PureVision multifocal
      contact lens or monovision with PureVision single vision lenses. After a 1-month
      trial, the following assessments of visual function were made: (a) distance,
      intermediate, and near visual acuity (VA); (b) reading ability; (c) distance and
      near contrast sensitivity function (CSF); (d) near range of clear vision; (e)
      stereoacuity; and (f) subjective evaluation of near vision ability with a
      standardized questionnaire. Subjects were then refitted with the alternative
      correction and the procedure was repeated. All measurements were compared between
      the two corrections, whereas the "low addition" multifocal lens was also compared
      with the "high addition" alternative. RESULTS: Distance and near VA were
      significantly better with monovision than with the multifocal option (p < 0.05).
      Intermediate VA (p = 0.13) was similar with both corrections, whereas there was
      also no significant difference in distance and near CSF (p = 0.29 on both
      occasions). Reading speeds (p = 0.48) and the critical print size (p = 0.90) were
      not significantly different between the two contact lens corrections, but
      stereoacuity (p < 0.01) and the near range of clear vision (p < 0.05) were
      significantly better with the multifocal option than with monovision. Subjective
      assessment of near ability was similar for both types of contact lens (p = 0.52).
      The high addition multifocal lens produced significantly poorer distance and near
      CSF, near VA, and critical print size compared with the low addition alternative.
      CONCLUSIONS: Monovision performed better than a center-near aspheric simultaneous
      vision multifocal contact lens of the same material for distance and near VA
      only. The multifocal option provides better stereoacuity and near range of clear
      vision, with little differences in CSF, so a better balance of real-world visual
      function may be achieved due to minimal binocular disruption.

PMID- 19156010
TI  - Proteins identified from care solution extractions of silicone hydrogels.
AB  - PURPOSE: The purpose of this study was to investigate the quantity and identify
      the proteins extracted from two different types of silicone hydrogel contact
      lenses by several multipurpose care solutions after 1 day of wear. METHODS: Ten
      subjects were recruited to wear galyfilcon A lenses (Acuvue Advance, Vistakon)
      followed by lotrafilcon B lenses (O2 Optix, CIBA Vision) each for four
      consecutive days. Each day, subjects inserted a new pair of lenses for 8 h of
      wear after which both lenses were removed using forceps (lenses were not rubbed
      or rinsed after removal). Lenses were pooled in one of four commercially
      available care solutions for a 24-h soak followed by precipitation, resuspension
      in water, and quantification by Bradford assay and identification by mass
      spectrometry. RESULTS: Protein recovery from care solutions was as follows
      (quantities are in microg/lens): AQuify (galyfilcon A: 0.56, lotrafilcon B:
      1.24), Complete MoisturePlus (galyfilcon A: 1.44, lotrafilcon B: 1.47), Opti-Free
      Express (galyfilcon A: 2.31, lotrafilcon B: 5.67), and ReNu MoistureLoc
      (galyfilcon A: 1.17, lotrafilcon B: 4.38). For each care solution, greater
      quantities of protein were removed from lotrafilcon B (3.19 +/- 2.19 microg/lens)
      than from galyfilcon A (1.37 +/- 0.72 microg/lens). Lactoferrin, lysozyme, and
      lipocalin were the most commonly identified, whereas various keratin compounds
      and other unique proteins were also detected. CONCLUSIONS: Opti-Free Express was
      consistently associated with the more efficient removal of proteins from these
      silicone hydrogels. More total protein was removed from lotrafilcon B than from
      galyfilcon A (approximately 2 x more protein) for all four care solutions, and 12
      total unique protein species were recovered from galyfilcon A, whereas only 10
      were recovered from lotrafilcon B. The higher quantities of protein extracted
      from lotrafilcon B may be due to stronger protein binding with this material
      and/or to differences in solution efficacy.

PMID- 19156011
TI  - Use of sunglasses in public outdoor recreation settings in Honolulu, Hawaii.
AB  - PURPOSE: Approximately, 20.5 million Americans (17.2%) older than 40 years have a
      cataract in at least one eye, and rates are expected to rise to over 30 million
      by 2020. Wearing sunglasses, especially early in life, may reduce the risk of
      cataracts. Meanwhile, little is known about the prevalence of wearing sunglasses
      in the United States, especially in areas with high ultraviolet radiation. The
      objective of this study was to assess the prevalence and predictors of wearing
      sunglasses in public outdoor recreation settings. METHODS: Systematic
      observations were made at beaches, parks and outdoor public swimming pools in
      Honolulu, Hawaii on sunny days between November 2005 and June 2007. Observations
      were conducted independently by two trained observers between 10:00 am and 4:00
      pm. During each observation period, each individual in the area was coded for
      gender, age category, clothing coverage, shade use, and use of sunglasses.
      RESULTS: A total of 5171 people were observed by two independent observers, and
      the inter-rater reliability use of sunglasses was excellent (Cohen kappa = 0.83).
      Overall, 33.0% of people wore sunglasses. chi analysis revealed that
      significantly more people (p < 0.001) wore sunglasses at swimming pools (35.1%)
      and parks (34.8%) compared to beaches (30.4%). Adults (41.6%) were more likely to
      wear sunglasses than children (12.3%; p < 0.001). Gender was not significantly
      associated (p = 0.3) with the use of sunglasses (males = 32.7%; females = 33.3%).
      Those wearing hats were significantly more likely (p < 0.001) to wear sunglasses
      (46.6%) than those with bare heads (28.4%). CONCLUSIONS: Direct observation in
      public outdoor recreation settings revealed that only one third of the population
      wore sunglasses. Further research should examine the use of sunglasses in other
      locations and investigate the effectiveness of interventions that promote the
      wearing of sunglasses in settings with risk for ultraviolet radiation exposure.

PMID- 19156012
TI  - Effectiveness of base in prism for presbyopes with convergence insufficiency.
AB  - PURPOSE: Although the treatment of symptomatic convergence insufficiency (CI)
      with base-in (BI) prism in adults has a strong theoretical foundation, there have
      been very few studies addressing its efficacy. The purpose of this study was to
      investigate whether the application of BI prism, using a novel progressive
      addition lens design which incorporates BI prism in the near portion only, could
      help alleviate the symptoms in presbyopes with CI. METHODS: A total of 29
      symptomatic CI subjects aged 45 to 68 years were examined. All subjects took the
      CI Symptom Survey V-15 (CISS) and scored >or=16 points. Each subject was assigned
      two pairs of progressive addition glasses made by the same manufacturer in a
      randomized sequence, one with BI prism and one with the same lens prescription
      but no prism (placebo). Subjects wore each pair of glasses for 3 weeks and
      completed the CISS at the end of the 3rd week. Symptom level measured with CISS
      was the major outcome measure. RESULTS: The mean (standard deviation) CISS score
      was 30.21 (9.30) at baseline and decreased to 13.38 (9.44) with the BI-prism
      glasses, vs. 23.62 (10.76) with the placebo glasses. There were significant
      differences between the baseline survey score and the score with the BI-prism
      glasses (p < 0.0001) and between the score with placebo glasses and the one with
      BI-prism glasses (p = 0.001). CONCLUSIONS: The progressive addition glasses with
      BI-prism were found to be effective in alleviating symptoms of presbyopes with
      symptomatic CI.

PMID- 19156013
TI  - Adhesion of Pseudomonas aeruginosa to orthokeratology and alignment lenses.
AB  - PURPOSE: To determine whether contact lenses designed for orthokeratology (OK)
      are colonized by greater numbers of bacteria compared with standard (alignment
      fitted) design rigid gas permeable lenses before and after lens wear. METHODS:
      Eighteen 1-year-old cats were randomly fitted with an OK lens in one eye and an
      alignment fitted (AF) lens in the other eye. Both lenses were made in the same
      diameter and central thickness and of the same material. Two separate wearing
      periods of 2 weeks and 6 weeks were used. After each wearing period, lenses were
      soaked in Pseudomonas aeruginosa (6294 or 6206) for 10 min. The lenses were then
      reinserted onto their respective corneas for a wearing period of 16 hours after
      which lenses were collected and remaining adhered bacteria quantified. Unworn
      control lenses were also soaked and bacteria enumerated for comparison. RESULTS:
      There were no significant differences in the number of bacteria adherent to
      unworn AF and OK lenses. Analysis of lenses after wear showed OK lenses retained
      significantly higher numbers of viable bacteria than AF lenses in all studies.
      CONCLUSIONS: OK lenses retain more bacteria than AF rigid gas permeable lenses
      after bacteria-loaded overnight lens wear. This may increase the risk for an
      infection in OK patients should suitable conditions be present. Specific
      education on the cleaning of OK lenses is essential.

PMID- 19156014
TI  - Blinking and tear break-up during four visual tasks.
AB  - PURPOSE: This study investigates the relationship between blinking, tear film
      break-up, and ocular symptoms for normal and dry eye subjects performing four
      different visual tasks. METHODS: Sixteen control and sixteen dry eye subjects
      performed four visual tasks (looking straight ahead, watching a movie,
      identifying rapidly changing letters, and playing a computer game) while blink
      patterns and fluorescein images of the tear film were videotaped. Pre and
      posttesting symptom questionnaires, querying the intensity of nine symptoms of
      ocular irritation, were completed by all subjects. Blink rate and blink amplitude
      were computed from digitized videos. The percentage of tear film break-up before
      the blink was calculated. RESULTS: Dry eye subjects had a significantly higher
      blink rate (p = 0.017, t-test). Both groups blinked significantly less during the
      game and letter tasks (p < 0.04, t-test). Partial blinks were common as were
      clusters or "flurries" of rapid blinks, but there was no significant difference
      in blink amplitude for control and dry eye subjects. Tear film break-up in normal
      subjects was typically inferior; whereas dry eye subjects showed more tear break
      up centrally and superiorly. Real-time video recording of tear break-up and blink
      behavior pointed to complex interaction between the two. Dry eye subjects shifted
      more toward intense ocular symptoms at posttesting (p < 0.05, Wilcoxon signed
      rank) than controls. Both groups showed a shift toward more corneal staining at
      posttesting (p < 0.05, Wilcoxon signed rank), which was typically inferior.
      CONCLUSIONS: Reduced and incomplete blinking along with increased tear film break
      up during normal visual tasks may explain the increased level of ocular
      discomfort symptoms reported at the end of the day, particularly in dry eye
      patients.

PMID- 19156015
TI  - Higher-order aberrations when wearing sphere and toric soft contact lenses.
AB  - PURPOSE: To determine the on-eye effect of spherical and toric contact lens
      design on higher-order aberrations (HOA). METHODS: Thirty eyes (15 subjects)
      entered a masked, randomized, cross-over study. Each eye was fitted with the
      spherical and toric lens of the following brands in random order: Acuvue Advance,
      Biomedics 55, Frequency 55, and SofLens 66. HOAs were measured using the Zywave
      II Aberrometer over a 6-mm aperture up to fifth order. A linear model accounting
      for the fixed effect of lens type and random effects of subject and eye was
      created. Paired t-tests were completed between lens brands within the spherical
      and toric lenses and between the spherical and toric lens within each brand. Best
      corrected visual acuity (VA) was measured and compared. RESULTS: No clinically
      meaningful differences in total HOAs were found between brands or between the
      spherical and toric lens within a brand. Positive spherical aberration (SA) was
      reduced by all spherical and toric lenses compared to wearing no lens by 0.07 to
      0.23 microm (p < 0.0001). Frequency toric induced the greatest change in SA. The
      thin-zone design lens (Acuvue Advance for Astigmatism) had a statistically
      different amount of vertical coma (-0.04 microm) than the three prism-balast
      toric lenses (0.11 to 0.23 microm; p < 0.0001). SofLens toric had the greatest
      amount of vertical coma, but better VA than Acuvue Advance for Astigmatism and
      Frequency toric. With the exception of Acuvue Advance for Astigmatism, toric
      lenses had greater absolute magnitude of vertical coma than their sphere
      counterparts (all p < 0.002). No other significant HOA differences were observed.
      CONCLUSIONS: Toric contact lenses with prism-ballast designs demonstrated more
      vertical coma, but better VA. Positive SA was reduced by spherical and toric
      contact lenses. The visual quality effect of lens design and material on induced
      HOAs warrants further investigation.

PMID- 19156016
TI  - Color vision panel tests: a metric for interpreting numeric analytic indices.
AB  - PURPOSE: Various systems have been proposed for quantifying arrangements of
      colored caps in panel tests of color vision. We examine Vingrys and King-Smith's
      (Vingrys and King-Smith. Invest Ophthalmol Vis Sci 1988;29:50-63) computed values
      for their different numerical indices derived and propose a metric for
      interpreting these index values. Our approach is based on performance of color
      normals when angular subtenses of the panel caps are reduced by changing the test
      distance. METHODS: Seven participants with normal color vision performed the
      panel tests at each of five viewing distances from 0.5 to 7.56 m (chromatic
      portions of the caps subtending 75 to 5 minarc). To obtain cutoff values for the
      numeric indices at the standard viewing distance under our viewing conditions, we
      also tested 69 unselected, volunteers with the Farnsworth D-15 and Lanthony
      desaturated D-15 panels. From each participant one eye, usually the worse, was
      included in analyses to find the 90th percentiles for each index, which we used
      as cutoff values. Many of the participants also made Rayleigh anomaloscope
      matches. RESULTS: For normal observers, values for the C-index (confusion) and
      for the S-index (polarity of an individual's pattern of cap reversals) begin to
      worsen when viewing distance increases beyond 2 m (corresponding to a subtense of
      15 minarc). Thereafter, increasing values of the indices (deteriorations in color
      vision) fall exponentially with distance. We find that the functions for the
      Farnsworth and Lanthony panels are so highly correlated that the same function
      can be used for both. The cutoff index values for our conditions, values that
      differ little from those reported by others, correspond to a viewing distance of
      about 2.5 to 3.0 m. CONCLUSIONS: An individual's color vision performance can be
      interpreted by relating it to performance of color-normals viewing the test caps
      at some non-standard distance. This is similar to Snellen notation for acuity.

PMID- 19156017
TI  - L-carnitine and short chain ester in tears from patients with dry eye.
AB  - PURPOSE: The tear film is essential for the integrity of the ocular surface. In
      ocular diseases such as dry eye syndrome (DES), tear film osmolarity is increased
      relative to normal physiological conditions. DES can be caused by deficiency in
      lachrymation, hyperevaporation, or surface alterations. Carnitines, shown to have
      osmoregulatory properties, are thought to regulate tear film osmolarity, thus
      protecting the corneal surface from damage. We investigated the presence of
      carnitine in tears, compared tear carnitine concentrations in healthy subjects
      and in DES patients and speculate on carnitine's potential role as a protective
      agent in the tear film. METHODS: Tears were collected from 10 healthy subjects
      and 10 DES patients. Carnitine levels were assessed by high performance liquid
      chromatography-mass spectrometry. RESULTS: Carnitine and its derivatives were
      detected in the tear samples. In DES patients, concentrations were substantially
      lower than in healthy subjects; the mean concentrations were L-carnitine, 3.27 +/
      0.80 and 8.94 +/- 0.50 microMol/L; L-acetylcarnitine, 1.66 +/- 0.50 and 3.05 +/-
      0.65 microMol/L; and L-propionylcarnitine, 0.30 +/- 0.11 and 0.57 +/- 0.13
      microMol/L, in DES patients and healthy subjects, respectively. CONCLUSIONS:
      Although increased tear film osmolarity has been previously observed in DES
      patients, our study showed lower carnitine levels in DES patients than in healthy
      subjects, rather than the increased levels expected, although a causal
      relationship between carnitine levels and hyperosmolarity has not been
      established. The damage to ocular surface cells because of exposure to hypertonic
      tear film observed in DES may be partially because of an imbalance in the
      concentration of carnitine molecules in the tear film relative to the ocular
      surface cells. We propose, therefore, that carnitine solutions may have a role in
      preventing the adverse effects of observed hyperosmolarity and suggest that
      further studies are now warranted to investigate the clinical application of
      carnitine in the treatment of DES.

PMID- 19156018
TI  - A Cochrane review of treatment for dysarthria following acquired brain injury in
      children and adolescents.
AB  - BACKGROUND: The expression ''acquired brain injury'' (ABI) incorporates a range
      of etiologies including cerebrovascular accident, brain tumour and traumatic
      brain injury. ABI is a common cause of disability in the pediatric population,
      and dysarthria is a common and often persistent sequelae associated with ABI in
      children. OBJECTIVES: The aim of this study was to assess the efficacy of
      intervention delivered by Speech and Language Pathologists/Therapists targeting
      dysarthric speech in children resulting from acquired brain injury. METHODS:
      Several electronic databases were searched up to January 2007. The review
      considered randomised controlled trials (RCTs) and quasi-randomised studies of
      children aged 3 to 16 years with acquired dysarthria grouped by aetiology (e.g.,
      brain tumour, traumatic brain injury, cerebrovascular accident). Both authors
      independently assessed the titles and abstracts for relevance (100% inter-rater
      reliability) and the full text version of all potentially relevant articles was
      obtained. No studies met inclusion criteria. RESULTS: Of 2091 titles and
      abstracts identified, full text versions of only three were obtained. The
      remaining 2 088 were excluded, largely on the basis of not including dysarthria,
      being diagnostic or descriptive papers, and for concerning adults rather than
      children. All obtained articles were excluded due to including populations
      without ABI, adults with dysarthria, or inappropriate design. Thus, no studies
      met inclusion criteria. CONCLUSIONS: The review demonstrates a critical lack of
      studies, let alone RCTs, addressing treatment efficacy for dysarthria in children
      with ABI. Possible reasons to explain this lack of data include 1) a lack of
      understanding of the characteristics or natural history of dysarthria associated
      with this population; 2) the lack of a diagnostic classification system for
      children precluding the development of well targeted intervention programs; and
      3) the heterogeneity of both the etiologies and resultant possible dysarthria
      types of pediatric ABI. Efforts should first be directed at modest well
      controlled studies to identify likely efficacious treatments that may then be
      trialled in multicentre collaborations using quasi-randomised or RCT methodology.

PMID- 19156019
TI  - A Cochrane review of treatment for childhood apraxia of speech.
AB  - BACKGROUND: The diagnosis of Childhood Apraxia of Speech (CAS) remains heavily
      debated, and there is no agreement upon the etiology for the disorder. Whilst
      there is some consensus on the potential broad array of presenting features of
      children with CAS, only three key features are recognised as ubiquitous for
      diagnosis: 1) inconsistent error production on both consonants and vowels across
      repeated productions of syllables or words; 2) lengthened and impaired
      coarticulatory transitions between sounds and syllables; and 3) inappropriate
      prosody. Despite the typically severe and complex presentation of CAS, there is
      little evidence reported on intervention approaches for the disorder, perhaps as
      a result of the ongoing deliberation over etiology and diagnosis. OBJECTIVES: The
      aim of this paper was to assess the efficacy of intervention delivered by Speech
      and Language Pathologists(s)/Speech and Language Therapists targeting CAS in
      children and adolescents. METHOD: Several electronic databases were searched up
      to January 2007. The review considered randomised controlled trials (RCTs) and
      quasi-randomised studies of children aged 3 to 16 years with CAS, grouped by
      treatment types (e.g., perceptual and instrumentally-based biofeedback treatment
      techniques). Two authors independently assessed references identified from the
      searches and obtained full text versions of all potentially relevant articles.
      RESULTS: Of 825 titles and abstracts searched, only 31 abstracts appeared to meet
      inclusion criteria. The remaining 794 papers were excluded predominantly on the
      basis of not including participants with CAS (e.g., focused on other
      developmental speech disorders or adult acquired apraxia of speech), or for not
      being intervention studies (i.e. being diagnostic or descriptive). All 31 full
      text articles obtained were excluded following evaluation as they did not meet
      inclusion criteria on design. CONCLUSION: The review demonstrates a critical lack
      of well controlled treatment studies addressing treatment efficacy for CAS,
      making it impossible for conclusions to be drawn about which interventions are
      most effective for treating CAS in children or adolescents.

PMID- 19156020
TI  - A germane link between piriformis muscle atrophy and lumbar disc herniation.
AB  - This article reports the case of a a 29-year-old girl with a right-sided
      sciatica. Magnetic resonance imaging of the lumbar vertebrae and the pelvic
      region detected a right L5-S paracentral disc herniation with descending S1 nerve
      root compression and atrophy in the right piriformis muscle. Magnetic resonance
      images of two other subjects -one with a known diagnosis of lumbosacral nerve
      root compression and one healthy individual without any low back pathology were
      also used in comparison. To the best knowledge of the authors, piriformis muscle
      atrophy associated with lumbar disc herniation is discussed for the first time in
      the Literature.

PMID- 19156021
TI  - Spanish adaptation of the Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39).
AB  - AIM: The stroke and aphasia quality of life scale-39 is an interviewer
      administered questionnaire that has been developed and validated in the United
      Kingdom to be applied to patients with chronic aphasia as a consequence of a
      stroke. The objective of this article was to translate the Stroke and Aphasia
      Quality of Life-39 Scale (SAQOL-39) into Spanish language, and evaluate its
      acceptability and reliability. METHODS: The cross-cultural adaptation of the
      SAQOL-39 into Spanish was carried out by following the translation and back
      translation method. Twenty three patients with long-term aphasia due to stroke
      were tested. The patients were interviewed twice in a period from 2 to 12 days.
      The acceptability of the Spanish SAQOL-39 was evaluated by examining the
      floor/ceiling effects and the missing data. The reliability was assessed by
      Cronbach's alpha (internal consistence) and intraclass correlation coefficients
      (test-retest reliability) for the overall scale and its subdomains. RESULTS:
      There were no difficulties to translate the original version into Spanish. There
      was good acceptability demonstrated by minimal missing data and floor/ceiling
      effects. Test-retest reliability for the overall score, and the subscales scores
      was 0.949 (0.854-0.944). Internal consistency analysis by Cronbach's a was 0.950
      (0.851-0.900). CONCLUSIONS: This small scale study provided preliminary evidence
      for the acceptability and reliability of the Spanish version of the SAQOL-39.
      Further testing in larger samples is needed to evaluate the validity of the
      scale, its sensitivity to change and to confirm its reliability.

PMID- 19156022
TI  - Intrathecal ziconotide and baclofen provide pain relief in seven patients with
      neuropathic pain and spasticity: case reports.
AB  - Seven cases of combination of intrathecal (IT) ziconotide and baclofen therapy in
      patients with refractory neuropathic pain and spasticity were reviewed. Five of
      the seven adult patients were receiving IT baclofen treatment when ziconotide was
      initiated. All five patients had experienced at least one previous failed IT
      treatment regimen. Pain intensity scores improved by a mean of 50.3% with the use
      of ziconotide-baclofen therapy. Mean time to onset of pain relief was 15 weeks,
      at a mean ziconotide dose of 3.7 microg/day. Within this group of patients,
      adverse events were observed in one patient, but they were not considered to be
      ziconotide related and subsequently resolved. The remaining two patients were
      receiving ziconotide treatment when baclofen was initiated. Pain intensity scores
      improved by 75% and 30%, respectively. Pain relief was evident at two weeks and
      one week, with corresponding ziconotide doses of 2.4 microg/day and 14.4
      microg/day, respectively. One patient in this group reported adverse events, but
      all resolved during continued treatment with the study drugs. Treatment regimens
      varied between patients in these case series; each regimen used a different
      titration strategy and different concentrations of ziconotide and baclofen.
      Combination IT ziconotide and baclofen therapy may be a treatment option for
      patients with neuropathic pain and spasticity. Future studies are warranted to
      determine the optimal dosing and titration schedules for ziconotide-baclofen
      usage.

PMID- 19156023
TI  - Treadmill exercise in early mutiple sclerosis: a case series study.
AB  - AIM: The effect of specific exercise therapy programs on the management of
      balance and walking disorders in multiple sclerosis (MS) patients have not been
      fully explained yet. Reproducible measurement systems are especially required to
      show their efficacy. The aim of the present case series study was to explore the
      feasibility of an aerobic treadmill rehabilitation protocol (endurance training
      protocol) and its effects on walking parameters, muscular activity and postural
      balance. An adequate instrumental measure set was adopted to provide evidence of
      minimal motor dysfunction, not quantifiable by means of standard clinical
      examination. METHODS: Three minimally impaired MS patients were enrolled. The
      patients underwent endurance training on a treadmill for four weeks.
      Posturographic assessment, energy cost measurement and gait analysis by
      basography and surface electromyography recordings were used as outcome measures.
      RESULTS: Energy cost during treadmill walking was generally reduced in the three
      patients after exercise. Indexes of both sway path and sway area used for
      postural stability measurement were reduced after exercise in two patients,
      particularly with eyes closed. Minor changes were observed in gait pattern in
      terms of foot placement. Muscular activity pattern tended to normalize after
      training. CONCLUSION: The aerobic treadmill exercise is feasible, safe and it may
      improve early anomalies of posture and gait in early MS patients. In the context
      of an impairment oriented rehabilitation approach, the set of instrumental
      measurements proposed seems to be able to identify subclinical anomalies in a
      very low degree of functional involvement on an individual basis.

PMID- 19156025
TI  - [Endothelial dysfunction in pathogenesis of venous transformation].
AB  - The article deals with the findings obtained by present-day studies in
      pathophysiology of venous outflow disorders. The authors highlight a considerable
      role of the endothelium of the vascular wall resulting from its lesion with
      metabolic products of activated leukocytes in the development of varicose
      transformation. Also studied was the dynamics of the endothelial dysfunction
      marker, i.e., the number of the circulating endothelial cells (CECs). In so
      doing, amongst the patients presenting with segmental subcutaneous varicosity
      with reflux along the superficial and perforating veins, endothelial dysfunction
      was revealed most frequently, i.e., in 91% of the cases. It was proved that the
      CEC index might be used as a marker of endothelial dysfunction in patients
      presenting with varicose disease. An increase in this parameter above 6 x 10(4)
      cells per 1 ml of blood should be considered as a reliable manifestation of an
      endothelial lesion in diseases of the peripheral veins. By the degree of severity
      of endotheliemia, one may judge of the activity of the process of varicose
      transformation of veins, which makes it possible to timely take appropriate
      corrective measures. A priority trend in medical treatment of venous
      transformation is assigned to diosmine-based phlebotonics.

PMID- 19156026
TI  - [State of microcirculation in patients with atherosclerotic-aetiology stage IV
      chronic arterial insufficiency of lower limbs].
AB  - The authors have studied the findings of the examination of and therapeutic
      outcomes in a total of one hundred and thirty-one patients diagnosed with
      atherosclerotic-aetiology stage IV chronic arterial insufficiency of the lower
      extremities. Of these, the dynamic analysis of the tissue blood flow on the
      background of haemodynamically efficient direct revascularization of the lower
      limbs was carried out in ninety-six patients. In a further 35 patients, a
      comprehensive instrumental examination of the blood flow on the background of
      chronic critical ischaemia was complemented by evaluating the morphological
      alterations in the skin of the foot of the affected extremity. The findings
      obtained during the examination made it possible to single out three types of
      morphofunclional alterations in the micro-circulaiory bed (i. e., irreversible,
      severe reversible, and moderate), as well as to trace the patterns of
      transformation of the tissue blood flow in each of them on the background of
      efficient direct revascularization.

PMID- 19156027
TI  - [Feasibility study of perftoran for protection of the brain from ischaemia in
      operations on extracranial arteries].
AB  - AIM: To substantiate administration of <<Perftoran>> for prevention of cerebral
      ischemia in operations on extracranial arteries. MATERIAL AND METHODS: The
      present prospective randomized trial included a total of 50 patients having
      endured various operative interventions on extracranial arteries. Of these, 24
      subjects were additionally given <<Perftoran>> in order to prevent ischaemic
      complications. Conventionally accepted methods of protection were used in 26
      patients. The degree of cerebral ischaemia during surgery was assessed by means
      of monitoring the lactate content in the blood from the internal carotid artery
      and internal jugular vein on the side of the operation performed. Also, as an
      indirect method aimed at evaluating intraoperative cerebral ischaemia we used
      monitoring of transcutaneous oxygen tension (TcPO2) on the side of the surgical
      intervention with the placement of the appropriate sensor in the temporal region.
      RESULTS: The patients receiving perftoran additionally in order to prevent
      cerebral ischaemia showed a statistically reliable decrease in the blood lactate
      level at all stages of the operation. Besides, with the statistically similar
      levels of TcPO2 in the both groups at the stage prior to pinching the major
      arteries amongst the patients given perftoran the decrease in TcPO2 at the
      subsequent stages was significantly lower. CONCLUSION: Administration of
      perftoran during surgery on the extracranial arteries made it possible to
      substantially improve cerebral oxygenation, rendering it stable at all stages of
      the surgical intervention. Combining this method with other techniques aimed at
      protecting the brain makes it possible to increase safety of the operations by
      promoting additional protection from circulatory hypoxia in multifocal lesions of
      the carotid arteries and arteries of the circle of Willis.

PMID- 19156028
TI  - [An ultrasonographic study of the major arteries of the neck in patients with
      rheumatoid arthritis].
AB  - We examined a total of 125 patients, of whom 70 suffered from rheumatoid
      arthritis (RA). The comparison group was composed of 40 patients diagnosed with
      osteoarthrosis deformans (OD) and 15 with atherosclerosis of the major arteries
      of the head (MAH). The control group consisted of 40 subjects randomized by sex
      and age. Studied were the carotid, vertebral arteries and the cerebral blood flow
      by means of colour duplex scanning on the unit "Vingmed system, 5, Norway, 2002".
      Patients with RA as compared with those from the control group showed thickening
      of the vascular wall of the carotid arteries, especially manifested in patients
      with seropositive rheumatoid arthritis and in those suffering from RA with
      systemic manifestations of the disease. The findings obtained by the duplex
      scanning in patients with RA as compared with those of the control group and OD
      patients demonstrated an increased number of stenotic lesions of the carotid and
      vertebral arteries particularly pronounced in seropositive RA and RA with
      extraarticular manifestations of the disease. Statistically reliable findings
      were obtained while studying the deformities of the carotid arteries. Comparing
      the RA groups revealed significant differences: in the group of patients
      suffering from RA with the systemic manifestations noted was an increased
      percentage of the kinking along both the common carotid artery (chi(2) = 1.76;
      NS) and the interpal carotid artery (chi(2) = 8.44; p = 0.01). The findings
      obtained in the present study strongly suggest that in RA patients there take
      place alterations in the IMC in the form of a thickening with disordered
      differentiation of the intima-medial layers and the lesion of the cardiovascular
      system, which is characterized by an early development of atherosclerosis. The
      degree of atherosclerotic alterations is associated with the presence of systemic
      manifestations of RA, high activity of the inflammatory process, and
      seropositivity by the rheumatoid factor.

PMID- 19156029
TI  - Rheolytic thrombectomy: possibilities and first results.
AB  - The present study was undertaken to investigate the possibilities of using the
      method of rheolytic thrombectomy (hereinafter referred to as RTE) in surgical
      practice, and to assess its immediate outcomes in treatment of thromboses of
      arteries and veins of the lower extremities, as well as transjugular intrahepatic
      portosystemic shunts (hereinafter referred to as TIPS). We have gained experience
      in carrying out a total of 33 rheolytic thrombectomies with the help of the
      system JET 9000 (R) using the Xpeedior catheter in a total of thirty-one 43-to-87
      year-old patients. Twenty-four interventions were performed for acute thromboses
      of arteries and shunts of the lower limbs, five - in patients presenting with
      floating thrombi in the inferior vena cava, and four operations were carried out
      in patients diagnosed with thrombosis of the segment after TIPS. In the group of
      the patients with thromboses of the arteries of the lower limbs (n=19), in 16
      patients RTE resulted in restoration of >50% of the arterial lumen. In three
      patients of the same group, we managed to restore the lumen by only 50% and less.
      In the group of patients with thromboses of the shunts (n=5), RTE with a
      successful angiographic outcome was performed in three patients. In yet another
      patient, the lumen was restored only by 50%, and in a further one patient, the
      lumen of the shunt we failed to restore. Nineteen patients underwent a total of
      13 balloon angioplasties (BA), 4 stenting interventions, and 2 regional
      thrombolytic procedures. Two patients after RTE and V A were subjected to
      postdilatational endarterectomy. In one patient RTE from the shunt was
      supplemented with plasty of its proximal anastomosis with a synthetic patch. In
      two patients, RTE was complicated by embolism of the deep femoral artery. In the
      group consisting of five patients diagnosed with floating thrombi of the inferior
      vena cava, a successful outcome was observed only in two. In patients presenting
      with thromboses of the stems following TIPS in all the cases we managed to
      completely restore patency of the shunts. Later on, three patients were found to
      have developed rethrombosis of the shunt. In two cases after RTE, haemolysis was
      observed to ensue, followed by the development of acute renal insufficiency. The
      remote results were followed up in the group of the patients with thromboses of
      the arteries and shunts of the lower limbs within the terms up to 24 months.
      Patency of the remodelled segments was preserved in seventeen patients (77.3%),
      and five patients (22.7%) were subjected to amputation of the affected lower
      extremity. Hence, the initial experience gained in using RTE gives certain hopes
      in treatment of patients presenting with acute arterial and venous thromboses of
      various localization, owing to its due safety, minimally invasive nature, and
      high efficiency, especially in patients with severe accompanying pathology.

PMID- 19156030
TI  - [Extended indications for percutaneous coronary interventions after successful
      thrombolysis].
AB  - The study compared the efficiency of percutaneous coronary interventions (PCI)
      into infarction-related coronary artery (IRCA) in high-risk patients with acute
      myocardial infarction (AMI), that were fulfilled 12-24 hours since the pain
      syndrome onset or during recurrent ischemic episodes 3 days after successful
      thrombolysis. In the first group (68 patients) invasive restoration of blood flow
      was fulfilled in 3 days (at average 48 hours) after AMI onset due to recurrent
      ischemia. In the second group (56 patients) IRCA recanalization was fulfilled in
      12-24 hours (at average 20 hours) since pain syndrome onset due to clinical signs
      of unfavorable outcome high risk. IRCA recanalization was successful in 91% and
      97% of cases in the first and second groups, respectively. In all cases injection
      of contrast media Ultravist 370 was diagnostically significant and visualized
      coronary arteries free of adverse events. In control group (conservative
      treatment) IRCA occlusion or subtotal stenosis was diagnosed in 18% and 39% of
      cases, respectively; stenosis >75% and <75% - in 27% and 16%, respectively.
      CONCLUSION: in high-risk patients with AMI percutaneous coronary interventions
      into IRCA can be effective 12-24 hours after successful thrombolytic therapy.

PMID- 19156031
TI  - [Errors in examination and management of patients with lower limb varicosity and
      their role in development of a relapse of the disease].
AB  - Analyzing the literature of the recent years and own clinical experience gained
      in management of patients diagnosed with recurrent varicose disease indicate that
      along with the progression of the disease one of the main causes of its relapses
      are certain medical errors leading to the development of relapsing varicosity of
      the lower limb veins. Moreover, the number of medical errors often appears to
      considerably exceed the total number of the patients in whom they were revealed,
      i. e., several and more medical errors would have been made sequentially in one
      and the same patient at various stages of the examination. The present work is
      based on the findings obtained from a comprehensive examination and comparative
      analysis of the condition of the patients presenting with recurrent varicosity of
      the veins of the lower extremities, and the errors we revealed to have been made
      during the prior examination and surgical treatment of the latter. The errors
      were subdivided into diagnostic, tactical, technical and organizational ones as
      follows: Diagnostic errors: missed in 195 (90%) patients at the moment of the
      primary examination turned out to have been incompetent perforating veins, in 82
      (38 %) -saphenopopliteal reflux, and in 12 (5.5 %) patients not revealed turned
      out to have been the signs of postthrombotic disease, dysplasia of venous valves
      and arteriovenous fistulas. Tactical errors: in 61 (28 %) patients exceeded had
      been the indications for sclerotherapy, in 39 (18 %) - the indications for
      ligature methods, and 95 (44 %) patients were found to have had the trunk of the
      smaller saphenous vein not removed during the primary intervention. Technical
      errors: in 115 (53 %) patients we revealed a long stump of the greater saphenous
      vein and in 156 (72 %) that of the smaller saphenous vein, also left had been the
      trunk of the GSV in 43 (20 %) patients, and in 141 (65 %) subjects revealed were
      errors in treatment of the perforating veins of the crus and femur or a complete
      absence thereof. Our experience and the literature data indicate that the
      greatest number of complications, unfavourable therapeutic outcomes, and relapses
      of varicose disease occur during the management of phlebological patients in
      general surgical departments, with the attending physicians having insufficient
      training in phlebology. In our opinion, this quite delicate intervention should
      be performed by vascular surgeons, or surgeons duly trained in this specific
      modality.

PMID- 19156032
TI  - [Postoperative venous thromboembolic complications - real threat and modern
      preventive methods].
AB  - Prospective study included 244 patients, who underwent general surgery,
      gynecological or urological surgical interventions. The rate of postoperative
      venous thrombotic complications was analyzed in accordance with preventive
      strategy. It was shown that high-technology methods (both physical and
      pharmacological) in combination with other diagnostic and therapeutic
      interventions can improve the efficacy of PVTC prevention. Diagnostic algorithms
      for PVTC prevention and early diagnosis were developed and implemented into
      clinical practice.

PMID- 19156033
TI  - [The effect of oral contraceptives on the orthostatic diameter of lower limb
      major veins and its correction].
AB  - The study assessed the effect of combined oral contraceptives (COCs) on the lower
      limb major vein diameter during orthostasis and the possibility of its medical
      correction in 214 women aged 17-42 with chronic venous insufficiency (CVI),
      including 37 women with CEAP class C0, 76 - with class C1 and 101 - with class
      C2. Venous diameter was measured by duplex scanning; its increment between
      evening and morning measurements was calculated in 3 groups. In the first group
      (n=68) venous diameter was measured before COC indication and after 2 months of
      COC use. In this group the second assessment revealed significant increase in
      venous diameter among women with CVI classes C1 and C1. The second group (n=69)
      received COCs for at least 6 months; then COC was withdrawn and Flebodia 600 was
      indicated. In this group venous scanning was fulfilled during COC use and after 2
      months of its withdrawal and Flebodia 600 indication. Statistically significant
      decrease of orthostatic venous diameter was demonstrated for all scanned veins,
      evidencing diosmine-induced enhanced venous tone. The third group (n=77) did not
      interrupted COC intake and received Flebodia 600 concurrently. In this group
      venous measurements were fulfilled before and after 2 months of Flebodia 600
      intake. Significant, though not ubiquitous decrease of venous diameter was
      registered in this group. CONCLUSION: Phlebopathic effect of COCs was
      demonstrated in women with CVI, CEAP classes 0-1-2, as well as safety and
      efficiency of Flebodia 600. The results prove the feasibility of Flebodia 600
      indication for this population in case of COC intake.

PMID- 19156034
TI  - [Phlebopathies: aetiology and therapeutic management].
AB  - Phlebopathy is an ambiguously interpreted term. In the Russian literature, it
      implies functional disorders of the venous system, albeit not seriously
      jeopardizing, however substantially decreasing quality of life. Phlebopathies may
      be induced by different causes, not infrequently common with the risk factors of
      chronic venous insufficiency. The present work deals with the classification,
      pathogenesis and epidemiology of phlebopathies, as well as the results of the
      original studies on management of hormone-induces phlebopathy. Hormone-induced
      phlebopathy - symptoms of phlebopathy or chronic venous insufficiency induced by
      long-term intake of combined oral contraceptives (COCs). To optimize treatment of
      the pathology concerned, we examined three groups of female patients (112 women)
      suffering from hormone-induced phlebopathy of the lower limbs. In Group One
      patients, COCs were discontinued with no administration of venotonic agents.
      Group Two patients along with withdrawal of COCs were given Antistax, as well as
      elastic compression. Group Three patients continued receiving COCs accompanied by
      simultaneous treatment with Antistax. During the study, we determined the
      malleolar volume, also assessing the degree of subjective symptoms, and quality
      of life. It was shown that withdrawal of COCs alone was not sufficient to stop
      symptoms of phlebopathy. Antistax efficiently stops the majority of these
      clinical manifestations, even on the background of intake of contraceptives. The
      maximal effect was observed in discontinuation of the COCs, intake of Antistax
      and prescription of elastic compression.

PMID- 19156035
TI  - [Renal phlebohypertension and intervenous anastomoses in varicocele].
AB  - A total of two hundred and twenty-eight patients suffering from sinistral
      varicocele were diagnosed with renal phlebohypertension pressure varying from
      10/8 (9) to 30/28 (29) mmHg and stenosis (18), retroaortal compression (12),
      aortomesenteric compression (198) of the left renal vein with dilatation of the
      left testicular vein (198). The following operations aimed at the formation of
      vein-to-vein anastomoses were performed: a testiculoiliac anastomosis (182),
      testicular-inferior-epigastric anastomosis (22) and renocaval anastomosis (5).
      The operation according to the Ivanissevich's technique was carried out in
      nineteen patients. Varicocele was removed in all the operated on patients. A
      catamnestic follow-up examination was carried out in ninety-six operated on
      patients, and in eighty-two cases, hypertension in the left renal vein was
      eliminated.

PMID- 19156036
TI  - Internal carotid artery surgery in regional anesthesia at the Clinic of Surgery
      in Pilsen during the past 5 years.
AB  - A low percentage of perioperative complications and excellent long-term outcome
      following carotid artery surgery in Vascular Centers demonstrate the priority of
      surgical solutions in patients with significant findings on carotid arteries, in
      the prevention and treatment of ischemic cerebrovascular accidents. The group of
      patients from the Clinic of Surgery in Pilsen demonstrates the benefits of
      regional anesthesia during internal carotid artery surgery, both in terms of the
      patients' health and the financial costs incurred by the hospital.

PMID- 19156037
TI  - [Methods to protect the spinal cord and visceral organs in surgery of distal
      aortic dissections].
AB  - The problem of protecting the spinal cord and visceral organs in surgery of
      distal aortic dissections becomes increasingly important today because of a
      comparatively high incidence rate of complications. Paraparesis in type 3
      dissecting aortic aneurysm (DAA) is noted to occur in ischaemia of the spinal
      cord lasting more than 56.5+/-12 min and the inclusion into the blood flow of
      less than two responsible intercostal arteries. Multiple-organ insufficiency in
      type 3 DAA is observed in ischaemia of the visceral organs lasting more than
      36.4+/-6.9 min. While using profound hypothermia and circulatory arrest, fatal
      haemorrhage appears when the duration of the hypothermic arrest is more than 48+/
      13.5 min. The used methods aimed at protecting the spinal cord and visceral
      organs (perfusion-free technique with cerebrospinal fluid drainage, left artio
      femoral bypass, circulation arrest with deep hypothermia), optimization of the
      scope and technique of the operation, shortened duration of ischaemia, inclusion
      of the maximum number of the spinal arteries into the blood flow, the use of the
      system of collection and return of blood make it possible to expect a decreased
      number of complications.

PMID- 19156038
TI  - [Prediction of remote results after surgical management of patients presenting
      with atherosclerosis obliterans of the lower-limb arteries].
AB  - Forecasting the development of implants' narrowing appears to be one of the most
      important problems encountered in vascular surgery today. The present study was
      therefore undertaken to work out a comprehensive diagnostic methodology making it
      possible to reliably predict the development of stenosis of vascular anastomoses
      during the postoperative period in patients presenting with atherosclerosis
      obliterans. The work was based upon the findings obtained by examining a total of
      seventy-nine patients diagnosed with atherosclerosis obliterans of the lower
      limbs arteries, also including assessment of a large number of haemodynamic and
      immunological parameters both before and after reconstructive vascular
      interventions. The study showed substantial dynamics of a series of immunological
      and haemodynamic indices on the background of the operation and during the
      postoperative period. Based on the mathematical processing of the obtained data,
      the authors managed to reveal the factors playing a leading role in the
      development of stenosis, having also worked out a prognostic algorithm making it
      possible with high reliability to predict the development of stenosis of arterial
      anastomoses.

PMID- 19156039
TI  - [Sorption and contact-activating properties of the <<biograft-artery>>
      anastomosis zone: effect of suture material (communication II)].
AB  - The authors have carried out a comparative analysis of the interaction between
      two types of suture material with blood components, as well as studied the effect
      of heparin-mediated modification on the sorption and contact-activating processes
      in the zone of the anastomosis. The blood-compatible properties of the latter was
      assesses in vitro. It was determined that by minute 120 of the contact with
      blood, the largest amount of protein is had been absorbed by the anastomoses
      performed using the Prolene thread - 112 microg/cm2. Heparin-mediated
      modification made it possible to dramatically decrease the amount of the absorbed
      proteins. On the anastomoses performed with TiNi, additional treatment with
      heparin lead to an inconsiderable decrease in the protein amount. When
      identifying the absorbed proteins, we revealed dependence on the type of the
      suture material and modification with heparin. After a 60-minute contact with
      blood in the area of the anastomosis made with TiNi, absorbed were: albumin,
      immunoglobulins A, G, and transferrin. When using the Prolene thread, fibrinogen
      was noted to join. Additional heparinization exerted a favourable effect on the
      sorption processes in the area of the anastomosis wherein predominantly albumin
      and immunoglobulins A and G are predominantly absorbed. The parameters of the
      peak values and the rate of blood platelet aggregation were minimal in the area
      of the anastomoses done with TiNi with an additional treatment with heparin.

PMID- 19156040
TI  - [Simultaneous multi-storey bypasses in a poly-segmental lesion of lower-limb
      arteries in patients with critical ischaemia].
AB  - The article deals with therapeutic outcomes obtained in treating patients
      diagnosed with chronic critical ischaemia of the lower extremities, who were
      subjected to multi-storey shunting with the restoration of the major blood flow
      in the distal vascular bed and with the inclusion of the collateral bloodstream
      into the unaltered portions of the arterial segments. Also established was a
      distal anastomosis with the formation of an arteriovenous fistula. In the
      operated on patients, the manifestations of critical ischaemia of the lower limbs
      were coped with intraoperatively, and the check-up Dopplerograms taken during the
      follow-up period showed the presence of the major blood flow along the bypasses
      and more distally along the anterior tibial artery.

PMID- 19156041
TI  - [Short- and long-term complications of arterial reconstructions in gerontological
      patients].
AB  - The present work deals with analysing complications and causes of their
      development in the immediate and remote (5-year) period of dispensary follow-up
      after reconstructive arterial operations interventions in patients aged 70 years
      old and over, suffering from atherosclerosis obliterans of the lower-limb
      arteries. Based on considerable clinical material, the authors consider the main
      vascular, non-vascular and systemic complications, their incidence rate and
      character, depending upon the type of revascularization of the extremity
      involved. Also formulated herein are the conclusions on profitability and
      rationale of a particular surgical policy in treatment for chronic ischaemia of
      the lower limbs in elderly and aged patients.

PMID- 19156042
TI  - Aneurysm of aortocoronary bypass graft: two clinical case reports.
AB  - The article deals with the description of two clinical case reports of a rare
      complication following operations of aortocoronary bypass grafting, i. e.,
      aneurysms of aortocoronary bypass grafts. The diagnosis of an aneurysm of the
      bypass graft was in both cases made by means of modern methods of radiodiagnosis,
      namely, electron-beam tomography and multislice helical computed tomography.

PMID- 19156043
TI  - [Experience with primary coronary angioplasty in management of patients suffering
      from acute myocardial infarction].
AB  - The authors herein analysed the findings obtained in randomized studies carried
      out to compare the efficacy of percutaneous transluminal coronary angioplasty
      (hereinafter referred to as PTCA) and thrombolytic therapy for acute myocardial
      infarction (AMI). Some studies employed thrombolytic therapy with streptokinase,
      while others used plasminogen tissue activators as thrombolytic agents. Primary
      PTCA as compared with thrombolysis was noted to decrease the total lethality
      rate, lowering mortality related to cardiogenic shock, decreasing lethality
      amongst elderly and aged patients, decreasing the prevalence of stroke and
      secondary infarctions, as well as the incidence of repeat revascularizations. The
      obtained findings demonstrated that primary PTCA still remains a better means of
      management of patients with AMI as compared with thrombolytic therapy,
      irrespective of the thrombolytic agent used. The long-term forecasts in primary
      PTCA and coronary artery bypass are similar, with the average hospital stay in
      PTCA being, however, shorter as compared with that in coronary artery bypass and
      thrombolytic therapy. Hence, the authors came to a conclusion that primary PTCA
      is a more efficient method of management of AIM patients than thrombolytic
      therapy or coronary artery bypass. We also analysed the findings of randomized
      studies aimed at comparing the efficacy of primary balloon dilatation and
      stenting of the infarction-associated coronary artery, and came to a conclusion
      that primary stenting makes it possible to more efficiently, than balloon
      angioplasty, revascularize the infarction-affected myocardium, since stenting
      decreases the incidence rate of relapsing secondary revascularizations as
      compared with primary balloon dilatation. However, stenting possesses no
      advantages over angioplasty as regards the influence on the incidence rate of
      lethal outcomes and secondary myocardial infarctions. Using the syrolimus
      containing stents may improve the long-term prognosis in patients presenting with
      AMI. Preliminary administration of absiximab was observed to decrease the
      lethality rate amongst the patients subjected to primary angioplasty during the
      first 30 days following the development of AMI, exerting however no influence on
      the lethality rate during one year after the onset of AMI. Intravenous
      administration of beta-adrenoblockers as compared with primary angioplasty
      improves survival in AMI patients. Aspirin treatment before and after primary
      angioplasty appears to improve the remote prognosis following PTCA as compared
      with the patients having received no aspirin. We believe that beta-adrenoblockers
      and aspirin should be used in management of patients having undergone angioplasty
      of the infarction-associated coronary artery.

PMID- 19156044
TI  - [Minimally invasive surgery of the infrarenal aorta].
AB  - Over five decades having passed since the first report of J. Oudot on grafting of
      the abdominal aorta, reconstructive operations on the aortofemoral segment have
      become amongst the methods most commonly used in angiosurgery. However, despite
      the progress achieved in anaesthesiology, critical care medicine and surgical
      techniques, the traumatic nature of these interventions is still high, which
      predetermines the perioperative lethality rate amounting to 2-5 %. Certain
      progress has been related to the introduction of endovascular methods of
      treatment. However, these techniques have failed to solve the problem because of
      the presence of certain contraindications and limitations thereof. Further search
      for ways aimed at improving the outcomes of management of patients presenting
      with pathology of the infrarenal aorta has led to the introduction of minimal
      access surgery (MAS) widely used since the 1980's in various areas of surgery.
      The present article reviews the history and state of the art of minimally
      invasive surgery of the infrarenal aorta, giving a comparative evaluation of the
      three main techniques currently used, i. e., an open minimal access, "total"
      endovideosurgery, and a video-assisted minimal access. Also reflected herein are
      the main technical problems arising and encountered during these operations, and
      disadvantages of each of the methods. Special attention is paid to the problem
      concerning technical support of the minimally invasive operations, and
      limitations to the application thereof.

PMID- 19156045
TI  - [Review of annual meeting of the American Society for Vascular Surgery,
      Baltimore, USA, June 7-10, 2007].
AB  - Annual meeting of the American Society for Vascular Surgery took place in
      Baltimore (USA) from 7 to 10th June, 2007. Participants discussed actual problems
      of angiology, vascular and endovascular surgery. The conference was characterized
      by high scientific and organizational level.

PMID- 19156046
TI  - Effect of immunocorrection on surgical outcomes in patients with autoimmune
      aetiology vasculitis and vasculopathies.
AB  - The present study was undertaken to investigate and compare the outcomes of three
      options of preoperative preparation and postoperative management of patients
      presenting with autoimmune-aetiology vasculitis and vasculopathies, who had been
      subjected to angiosurgical interventions over a 7-year period. According to the
      aetiopathogenetic sign, the majority of the patients appeared to have
      thromboangiitis obliterans, non-specific aortoarteritis, primary and secondary
      vasculopathies. All the patients were age- and sex-matched and well comparable by
      the underlying disease, the level of lesions of the vascular bed, and the
      ischaemia burden. The study was performed retrospectively. A total of three
      options of preoperative preparation and management of the postoperative period
      were used: option one - treatment comprising plasmapheresis, immunoglobulins and
      biological immunomodulators; option two - using cytostatic agents and hormone
      therapy; and option three - consisting of conventional basic vascular therapy
      alone. The comparative analysis performed demonstrated a clear advantage of
      immunocorrection and efferent techniques of treating patients presenting with the
      pathology concerned. The use of the therapeutic-and-diagnostic algorithm we are
      suggesting herein would make it possible to avoid complications in the immediate
      postoperative period, to reduce the duration of the patients' hospital stay
      averagely by 10 days, and to prolong persistence of the obtained positive results
      by 11.5%.

PMID- 19156047
TI  - [Activation of intravascular microcoagulation of blood in patients with
      atherosclerotic gangrene of the lower limbs].
AB  - A prospective study was carried out in order to investigate the system of
      haemostasis in a total of sixty patients presenting with atherosclerotic gangrene
      of a lower extremity who were then subjected to high amputation. The operative
      intervention was preceded and followed by determining the following parameters:
      antithrombin III (AT-III), fibrinogen (FG), thrombin time (TT), activated partial
      thromboplastin time (APTT), prothrombin time (PT), the number of the soluble
      fibrin-monomeric complexes (SFMC) and D-dimers, euglobulin fraction clot lysis
      time, the amount and aggregation activity of blood platelets. The findings
      obtained while studying haemostasis in patients with irreversible ischaemia of
      the lower limbs demonstrated activation of the intravascular microcoagulation of
      blood prior to the operation. The immediate postoperative period was marked by
      preservation of the shortened APTT, high concentration of fibrinogen, elevated
      euglobulin clot lysis time, high concentrations of SFMCs and D-dimers of blood,
      which created conditions for the development of thrombotic complications even in
      a relatively stable course of the postoperative period. The authors underline the
      necessity of determining an optimal mode of prescribing and administering
      appropriate doses of direct anticoagulants in the early and immediate
      postoperative period, as well as that of making an appropriate decision of
      whether or not to use indirect anticoagulants for correction of haemostasis in
      these patients during the remote postoperative period.

PMID- 19156048
TI  - [Vasaprostan in treatment of chronic ischaemia of the lower limbs in patients
      with diabetes mellitus].
AB  - The article is dedicated to management of diabetic patients suffering from
      chronic critical ischaemia of the lower limbs treated with vasaprostan. The
      authors analysed herein therapeutic outcomes in a total of 156 patients with
      vasaprostan administered both as monotherapy and in a combination with surgical
      management. Good results were also obtained concerning prevention of ischaemic
      and pyo-necrotic complications in this cohort of patients and respectively a
      decrease of the number of high amputations.

PMID- 19156049
TI  - [Multispiral computed tomography-assisted angiography in diagnosis of diseases of
      the aorta and lower limb arteries].
AB  - PURPOSE OF THE STUDY: Our work was aimed at determining the diagnostic value of
      multislice computed tomography-assisted angiography in atherosclerotic lesions of
      the aorta and arteries of the lower limbs, taking into consideration the
      condition of the peripheral bed, as well as at making an angiographic assessment
      of the quality of the reconstructive operations performed. MATERIAL AND METHODS:
      Over the period from October 2005 to July 2006, multispiral computed tomography
      assisted angiography (hereinafter referred to as MSCTA) followed by an operative
      intervention was carried out in a total of 59 patients who were diagnosed with
      diseases of the aorta and arteries of the lower extremities. The average age of
      the patients was 59.1 years (range from 17 to 83 years). MSCTA was carried out
      using a 16-slice CT scanner (Somatom Sensation Cardiac 16, <<Siemens>>) during
      the arterial phase of injecting the non-ionic radiopaque material <<Ultravist>>
      (<<Schering>>, Germany). RESULTS: Studying the dissemination of the obliterating
      processes revealed an aneurysm of the abdominal portion of the aorta (n=10),
      while in the remaining cases atherosclerotic lesions were observed to be
      localized in the aorto-femoral (n=17) and femoropopliteal segments (n=32).
      Comparing the findings obtained by the comprehensive examination and analysis of
      the angiograms, we determined that the sensitivity, specificity and accuracy of
      MSCTA in the mentioned groups amounted to 96%, 92% and 94%, respectively.
      CONCLUSION: MSCTA performed using the novel software appears to be an alternative
      to other diagnostic methods of examining patients presenting with occlusive
      diseases of the lower limb arteries.

PMID- 19156050
TI  - [Problem of restenosis inside stents with an antiproliferative coating].
AB  - The article deals with a review of clinical studies carried out within the time
      period from 2003 to 2007. The review contains the data concerning restenoses of
      sirolimus- and paclitaxel-eluting stents, suggesting that the stents with an
      antiproliferative coating substantially diminished the acuity of the problem
      regarding restenoses but did not solve the problem completely. The incidence rate
      of restenoses remains high in patients with diabetes mellitus as well as in those
      with bifurcation stenoses, acute and chronic occlusions of coronary arteries.
      Analysing the published data the authors made a conclusion that during
      angioplasty of acute and chronic occlusions of coronary arteries preference
      should be given to sirolimus-eluting stents since they are most effective in
      prevention of restenoses inside stents in such lesions. Analysing the findings of
      clinical trials of drug-eluting stents showed efficiency and safety of such
      stents in treatment of in-stent restenoses. Patients with diabetes mellitus are
      exceptions to this rule, being poor candidates for drug-eluting stents, since the
      latter proved to exhibit low efficacy in these patients.

PMID- 19156051
TI  - Combined surgical management of a subclavian artery aneurysm complicated by an
      embolism to arteries of an upper limb.
AB  - The authors report herein a successful therapeutic outcome in a patient
      presenting with a posttraumatic subclavian artery aneurysm complicated by an
      embolism to arteries of an upper extremity, treated by means of endovascular
      prosthetic repair combined with a bypass-grafting operation on the arteries of
      the upper limb involved. A detailed description of the methodology and the course
      of the operation is provided. In the postoperative period, the clinical
      manifestations of ischaemia of the upper limb were completely relieved. The
      outcome of the operation was confirmed by intraoperative angiography, as well as
      by postoperative duplex scanning.

PMID- 19156052
TI  - [Stenting in vertebral artery dissection: an approach to management].
AB  - We describe a 56-years-old patient with spontaneous extracranial vertebral artery
      dissection, which was provoked by neck movements. Clinically dissection
      manifested with transient ischemic attacks in vertebrobasilar system which lasted
      during 3 months and often combined with occipital headache. Contrast angiography
      revealed subtotal stenosis of segment V1 of the right VA, extending from the
      ostium for a length of 1-1.5 cm with thread-like double lumen (true and false
      lumens). The rest part of V1 segment of the right VA was irregularly narrowed up
      to 40-50%. A good contrast filling of the rightVA beginning from segment V2 was
      carried out by the collateral circulation from thyreocervical trunk. No
      atherosclerotic plaques in extra- intracranial arteries were found. The patient
      was subjected to stenting of segment VI of right VA that resulted in a complete
      restoration of the arterial lumen. No postoperative complications were observed.

PMID- 19156053
TI  - [Surgical pathology of lower limb veins: from pathogenesis to prevention and
      management].
AB  - The paper reviews modern epidemiological, experimental and clinical data on
      chronic diseases of lower limb veins. In particular the latest data on
      pathogenesis of variceal disease and chronic venous insufficiency are discussed
      along with their relation to leukocytic-endothelial interactions.

PMID- 19156054
TI  - [Aneurysm of the popliteal vein. Review of the literature and a case report].
AB  - The article deals with a brief review of the literature dedicated to rather an
      uncommonly encountered pathology of the major veins, i. e., an aneurysm of the
      popliteal vein. Described herein are variants of the clinical pattern and
      possible complications, with an emphasis placed on methods of diagnosis and
      differential diagnosis of tumour-like neoplasms in the infragenicular region.
      Also presented is a clinical case report of successful treatment of a female
      patient diagnosed with a popliteal vein aneurysm.

PMID- 19156055
TI  - [Peculiarities of peripheral haemodynamics in patients with varicose disease of
      lower-limb veins complicated by trophic ulcers].
AB  - The work was dedicated to studying local, regional and systemic circulatory
      disorders in patients suffering from varicose disease of the lower extremities
      veins with accompanying trophic ulcers. The possibility of performing this work
      was determined by a diagnostic complex possessing high informative value
      (especially it concerns studying microcirculation). Based on the obtained
      findings we managed not only to evaluate severity of microcirculatory disorders
      but also to characterize them qualitatively, in particular to reveal the so
      called blood microshunting phenomenon. Pathophysiologically important is the
      development of inflammatory hyperaemia in the area of trophic ulcers, which is
      prognostically favourable for their healing. Proceeding from the above-mentioned,
      utterly true turned out the conclusion concerning the necessity to include
      microcirculation-improving pharmaceutical substances into the program of
      treatment of patients suffering from varicose disease of the lower-limb veins,
      especially those presenting with concomitant trophic ulcers, along with surgical
      intervention.

PMID- 19156056
TI  - [Endoscopic dissection of perforating veins: surgical and pharamacoeconomic
      aspects].
AB  - Analysed herein are the outcomes of endoscopic dissection of perforating veins
      (EDPV) in a total of 113 patients presenting with chronic venous insufficiency
      (CVI). Of these, 71 patients suffered from varicose disease (VD) and 42 subjects
      had postthrombophlebic disease (PTPD). 54.9 % of the patients were in CEAP class
      C5-6. All of them underwent EDPV combined with simultaneous phlebectomy or
      crossectomy. The control group consisted of 26 patients who endured the classic
      operation by the Linton technique. All those engaged underwent ultrasonograp-hic
      angioscanning, with part of them being subjected to distal phlebography.
      Postoperative complications were observed in 2.65 % of the Study Group patients
      subjected to the EDPV procedure combined with phlebectomy, and in 34.5 % of those
      who had endured the Linton's operation. Both subjective and clinical assessment
      of surgical outcomes made it possible to define the obtained results as good in
      82.3% of cases, as fair in 14.16%, and in four patients with PTPD, the results
      were defined as poor. The hospital stay following surgery in the Study Group
      patients amounted to 7.3+/-0.54 bed days, while in those of the Comparison Group
      it was 21.2+/-0.74 bed days. The obtained findings make it possible to conclude
      that the scope of surgical interventions in patients presenting with CEAP class
      C4-6 CVIs should in the majority of cases amount to simultaneous EDPV and radical
      venectomy. Such policy reduces the duration of the hospital stay 2.7-fold, with a
      1.76-fold decrease in the treatment costs.

PMID- 19156057
TI  - [Comprehensive outpatient treatment of varicose disease of the lower limbs].
AB  - The article deals with the findings obtained in examining a total of 8,000 people
      presenting with varicose disease of the lower extremities. The examination
      included a clinical (physical) examination and coloured duplex scanning of the
      lower-limb veins. The examination was carried out in outpatient conditions,
      whereas surgical treatment was performed either out-patiently, or at a <<one
      day>> hospital. Revealing complete valvular insufficiency of the great saphenous
      vein was followed by surgical treatment - intraoperative stem catheter
      scleroobliteration (SSO) or short-term screening and postoperative puncture
      sclerotherapy. Detecting partial valvular insufficiency of the greater saphenous
      vein (pathological sapheno-femoral reflux only in the vertical position) was
      managed by applying the principle of the so-called <<incremental radicalism>>: i.
      e. the patients were subjected to the procedure of puncture sclerotherapy of
      varicose veins on the crus in ambulatory conditions to be followed by secondary
      ultrasonographic scanning with permanent dynamic follow-up. The cases of
      preserved reflux along the greater saphenous vein were subjected to
      sclerosurgical management. Valvular insufficiency of perforating veins was coped
      with by minimally invasive surgical interventions: subtotal endoscopic dissection
      of incompetent perforating veins, suprafascial ligation from a miniaccess and
      echosclerotherapy of the perforating veins. Also performed were histological and
      histochemical studies of the portions the greater saphenous vein and surrounding
      tissues procured during cross-ectomy of the sapheno-femoral anastomosis in 43
      patients, who had endured preliminary puncture sclerotherapy on the crus. Good
      functional and cosmetically pleasing outcomes were achieved in the majority of
      cases. In 75% of the patients with partial valvular insufficiency of the greater
      saphenous vein, we managed to avoid operations since repeat ultrasonographic
      study revealed no pathological veno-venous shunts.

PMID- 19156058
TI  - [Transillumination-assisted phlebectomy with the help of the TriVex system in
      comprehensive management of varicose disease of lower-limb veins].
AB  - The present work was undertaken to evaluate a new minimally invasive method of
      surgical management of varicose disease by means of the TriVex unit. The method
      is based on transillumination of saphenous veins in an aqueous medium, which
      makes it possible to perform radical removal thereof form separate punctures
      under visual control with the help of a specially designed vein stripper.
      Transillumination-assisted phlebectomy (TIP) was compared with microphlebectomy
      (MPE) according to the Varady's technique. We operated on a total of one hundred
      and eight patients suffering from varicose disease of the lower extremities. All
      of them underwent duplex scanning of the veins. Group One (study group) was
      composed of fifty-six patients subjected to TIP within the scope of a
      comprehensive treatment for varicose disease. Group Two consisted of fifty-two
      patients who were subjected to removal of varicosely altered affluents on the
      crus by means of microphlebectomy. The results of surgical management for
      varicose disease were analysed according to the following parameters, the
      duration of a surgical intervention, intensity of the pain syndrome in the
      postoperative extremity, a cosmetic outcome by visual analogue scales, and the
      incidence rate of complications. The obtained findings demonstratively showed
      that the duration of the operation in the study group was substantially shorter,
      averagely amounting to 35.5+/-6.2 minutes, as compared with as long as 65.0+/-6.2
      minutes (P<0.0001) in the control group. The number of incisions in the study
      group turned out to be also significantly less than that in the control group,
      amounting to 4.0+/-1.3 vs. 12.0+/-2.5 (p<0.0001), which largely contributed to
      both a decrease in the level of the pain syndrome and obtaining aesthetically
      pleasing cosmetic outcomes. Hence, TIP being a minimally invasive procedure in
      surgical management of varicose disease, by its clinical efficiency appeared to
      be not inferior and at least equivalent to microphlebectomy, displaying at the
      same time certain advantages over the latter, consisting in the very positive
      cosmetic outcome obtained, a lesser operative injury inflicted, and shorter terms
      of rehabilitation of the patients involved.

PMID- 19156059
TI  - [Prognostication of neurological complication risk after descending and
      thoracoabdominal aortic aneurysm repair].
AB  - Neurological complications after descending and thoracoabdominal aortic aneurysm
      (TAAA) correction procedures remain a serious challenge. Their prevention implies
      proactive approach to manageable risk factors: diagnosis and preoperative
      correction of latent renal failure [odds ratio (OR)=4.72; p=0.08] and
      minimization the cross-clamp time (OR=7.0; p=0.03). Extended TAAAs, especially
      type 1 and 2, (OR=8.5; p=0.03) must be operated only in facilities with
      sufficient experience in such reconstructions. Prognostic model was suggested to
      calculate precisely the risk of paraparesis. TAAA correction <<without
      perfusion>> is accompanied by 1.45-fold higher risk of neurological complications
      then after procedures that are accomplished under protection.

PMID- 19156060
TI  - [Surgical correction of infrarenal abdominal aorta aneurysms].
AB  - The authors compare various surgical strategies of infrarenal abdominal aorta
      aneurysm (IAAA) repair based on the experience of the Department of
      Cardiovascular Surgery, Urban Clinical Hospital No.81. Total 198 patients
      underwent aneurysm resection and grafting through conventional (90) or
      minilaparotomy (108) approaches. Mini-approach was shown to improve significantly
      both perioperative course and outcomes of IAAA correction. The main advantage of
      this approach comprised limited invasiveness together with sufficient exposure of
      abdominal aorta and its branches. Abandoning small bowel evisceration helps to
      preserve ther-moregulation and achieve volemic homeostasis with less fluid
      volume. Postoperative period after surgical mini-approach was characterized by
      shorter period of mechanical ventilation and ICU stay, earlier restoration of
      bowel motility, conversion to usual nutrition, patient mobilization and
      discharge. Minimally invasive technology significantly broadens feasibility of
      radical aortic reconstructions for patients with serious cardio-vascular
      comorbidities.

PMID- 19156061
TI  - [Surgical decision-making in patients with a concomitant lesion of renal arteries
      and aortic arch branches].
AB  - The article deals with analysing the outcomes following surgical management of
      one hundred and six patients presenting with lesions of the renal arteries.
      Twenty-eight (25.4%) of the 106 patients operated on for lesions of the renal
      arteries were found to have a concomitant lesion of the aortic arch branches.
      Also suggested herein is a method aimed at determining the staging of
      reconstructive operations on the aortic arch branches and renal arteries, which
      is based upon the authors' own technique specifically devised for quantitative
      assessment of tolerance of the brain to ischaemia, i. e., determining the
      autoregulatory reaction of the cerebral vessels. This would make it possible to
      determine the sequence of reconstructive interventions to perform on the aortic
      arch branches and renal arteries, and hence dramatically diminish the rate of
      postoperative cerebrovascular complications.

PMID- 19156062
TI  - [Anatomic and surgical background for splenorenal venous transposition].
AB  - Unilateral portalization of adrenal and renal blood is used in clinical practice
      for arterial hypertension, chronic hepatitis and type 1 diabetes mellitus
      management. Left-sided renoportal venous anastomosis (RPVA), spleen vessel
      ligation and unilateral adrenalectomy (if indicated) are the technical backbone
      of the intervention. This operation was used for 50 patients with chronic
      hepatitis. Ten of them were investigated 15-19 years postoperatively. Positive
      effect on the disease progression was found in the absence of negative
      consequences for liver, kidneys and spleen. Ultrasonography has demonstra-ted
      patent anastomosis in all patients. In early postoperative period hyperthermia
      and epigastrial pain were registered in 14.3% of cases as a consequence of
      thrombosis in ligated spleen vein stump. The paper describes the development of
      splenorenal venous transposition (SRVT) technique as an improved variant of
      adrenal and renal blood unilateral portalization, in which spleen vessel ligation
      is replaced by splenorenal end-to-end anastomosis. The study included 111
      cadaveric experiments. The technique of surgical intervention is described, its
      clinical requirements and potential obstacles. It is shown that SRVT can be
      fulfilled in 52.1% of cases with autovein graft. SRVT is more laborious and rare
      intervention, then single left-sided RPVA and must be initially practiced on
      cadavers. Indications for SRVT may include arterial hypertension, chronic
      hepatitis and type 1 diabetes mellitus.

PMID- 19156063
TI  - [Surgical policy in patients aged 70 years and over presenting with grade iv
      chronic ischaemia of lower limbs].
AB  - The present work deals with a currently important problem concerning surgical
      decision-making in treatment of lower-limb critical ischaemia in elderly and aged
      people. A total of fifty-three 70-and-more-year-old patients presenting with an
      ulcerative-and-necrotic lesion of soft tissue of the crus and foot underwent
      treatment at Hospital of War Veterans No?2. They were subdivided into two groups
      depending on the level (height) of occlusion, and each of the groups was further
      subdivided into subgroups of patients subjected to the classical for the given
      localization of the lesion shunting operations, to compare the latter with less
      traumatic but at the same time less effective minor and non-anatomical
      reconstructions. Statistical analysis of the therapeutic outcomes in the
      immediate and remote (2-year) follow-up period revealed that comparing the iliac
      femoral and cross femoro-femoral reconstructions, the best results were obtained
      after extra-anatomical operations. While comparing the femoropopliteal bypasses
      and profundoplasty showed that the obtained therapeutic outcomes were similar
      with certain advantage of the routinely performed shmting reconstructions. Based
      on the obtained findings, a conclusion was made on efficacy the principle of not
      maximal but sufficient revascularisation of lower-limb tissues owing to a
      predominant use of minor and non-anatomical reconstructions.

PMID- 19156064
TI  - [Surgical treatment of an aneurysm of the superficial femoral artery 40 years
      after an injury: a case report].
AB  - Presented herein is a case report of a male patient with a posttraumatic aneurysm
      revealed 40 years after an injury. The presence of a foreign body in the lumen of
      the artery for such a long time had had no manifestations and was detected by
      ultrasonographic duplex scanning. The patient was subjected to resection of the
      aneurysm of the superficial femoral artery on the right lower limb with
      prosthetic repair performed by a reversed autovein.

PMID- 19156065
TI  - Primary aortoesophageal fistula: a rare variant of a ruptured chronic
      posttraumatic dissecting aneurysm of the descending thoracic aorta.
AB  - Presented herein is own experience in successful management of a female patient
      diagnosed with a primary aortoesophageal fistula secondary to a rupture of a
      chronic posttraumatic dissecting aneurysm of the descending thoracic aorta into
      the oesophagus. The contained herein review of the literature deals with the
      problems concerning surgical policy of and indications for different variants of
      reconstructive operations on the aorta and oesophagus.

PMID- 19156066
TI  - [Successful surgical treatment of a patient with true aneurysms of common carotid
      arteries and infrarenal abdominal aorta].

PMID- 19156067
TI  - Surgical management of multiple posttraumatic arteriovenous fistulas of femoral
      vessels.
AB  - Presented herein are two case reports concerning surgical management of
      posttraumatic arteriovenous fistulas of femoral vessels. Case 1. A 45-year-old
      female patient attended with a history of a shotgun injury wound of her left
      femur and crus sustained when a girl of eight. She sought medical attention for a
      progressively deteriorating condition, accompanied by pain, and breathlessness
      dyspnea at rest. Detected were multiple fistulas between the deep femoral artery
      and superficial femoral artery and femoral vein. Management consisted in
      separation of the arteriovenous fistulas, followed by prosthetic repair of the
      deep femoral artery. Case 2. A 32-year-old male patient after an accidentally
      inflicted shotgun injury of the his left femur underwent within a time period of
      3 year three vascular operations including ligation of the deep femoral artery
      and femoral vein followed by having later on developed secondary lymphedema of
      his left lower limb and pronounced manifested chronic venous insufficiency.
      Management included dissociation of the numerous arteriovenous fistulas between
      the branches of the deep femoral artery and the common femoral artery, as well as
      between the superficial femoral artery and femoral vein.

PMID- 19156068
TI  - [Comparative results of endoscopic operations on account of soft tissues purulent
      diseases].
AB  - The results of open and endoscopic operations in 430 patients with purulent soft
      tissue diseases are comparatively studied. Hospital stay after the endoscopic
      treatment averaged 11,6+/-1,1 days. 90,8% of those, who were treated
      endoscopically, has completely recovered during the hospital stay and didn't
      require further treatment. 31,6% of patients experienced a suppuration of the
      postoperative wound, which called forth the conversion to the open operative
      technique. These patients had an average hospital stay of 15,6+/-2,1 days. The
      hospital stay of the patients treated traditionally with wide opening of the
      wound and secondary sutures, averaged 19,3+/-1,8 days. The hospital stay of
      patients with a complicated disease course was 26,4+/-3,4 days.

PMID- 19156069
TI  - [Diagnostics and treatment of abdominal injuries with retroperitoneal organs
      involvement].
AB  - The results of treatment of 66 patients with non-gunshot abdominal injuries,
      involving retroperitoneal organs, are described. Preoperative clinical and
      ultrasound investigations are not accurate enough to diagnose retroperitoneal
      lesions, which were diagnosed intraoperatively in 57,6% of patients. In 97%
      retroperitoneal haematoma was located 2-10 sm from the posterior parietal
      peritoneum. In case of aorta injury, postcava or renal injury grade IV,
      retroperitoneal haematoma is large and bulging, though absence of these signgns
      does not exclude serious injuries of retroperitoneal organs and structures.
      Retroperitoneal cavity revision by the dissection of the wound canal can provoke
      further bleeding, so it should be performed only after visualization and cross
      clamping the afferent vessel.

PMID- 19156070
TI  - [Gunshot wounds of the large intestine].
AB  - The results of treatment of 262 patients with gunshot wounds of the large
      intestine are described. 207 (79%) patients had colic injuries and the rest 55
      (21%) - gunshot wounds of the rectum. Authors adduce and substantiate the
      differential approach to each case, taking into consideration various factors,
      such as localization, size of the wound, grade of bacterial contamination and
      peritonitis etc In case of an injured colic segment resection necessity,
      obstructive resection was preferred. In case of intraperitoneal rectum injury
      wound closure with decompressive sigmostomy was justified. Extraperitoneal rectum
      injury requires surgical debridement without intestinal wall reconstruction and
      further sphincteroplasty. Postoperative lethality was 26,6% for colic injuries
      and 34,5% for rectal injuries. 85 patients experienced further reconstructive
      operations.

PMID- 19156071
TI  - [Endoscopic treatment of gastric polyps].
AB  - Data of 258 patients with gastric polipi is analyzed. Endoscopic polypectomy with
      further microscopical analysis was performed in 218 patients. The method of
      preoperative submucosal drug injection is proposed. It allowed to decrease the
      number of postoperative bleedings and recurrences.

PMID- 19156072
TI  - [Pathogenetic approach to the treatment of esophageal anastomosis failure].
AB  - The original method of esophageal anastomosis failure treatment and prophylaxis
      was used in 2190 patients. The method involves a device, providing a continuous
      irrigation of the anastomosis area with antiseptic and prevents contact between
      the suture line and gastric contents. It allowed to decrease of anastomosis
      failure to 0,6%. Postoperative lethality after operations performed on account of
      gastric cancer was 2,2% and 6,5% after operations on account of esophageal
      cancer. None of the patients had died due to esophageal anastomosis failure
      during the last 5 years.

PMID- 19156073
TI  - [Mini-invasive technologies for the acute pancreatitis treatment].
AB  - Results of treatment of 2415 patients with acute pancreatitis, including 285
      cases of the acute necrotizing pancreatitis, are analyzed. The algorithm of
      diagnostics and treatment of this category of patients is worked out and
      successfully applied. The comparative results of the acute pancreatitis treatment
      before (1995-1999) and after (2000-2005) introducing the algorithm to practice
      are analyzed. Thus, the rate of postoperative complications decreased from 16,7
      to 4,95% and postoperative lethality came down from 25 to 9,1%.

PMID- 19156074
TI  - [The treatment of gastoduodenal ulcer bleeding].
AB  - Treatment data of 1279 patients with gastroduodenal ulcer bleeding are analyzed.
      Outcomes are comparatively analyzed depending on the chosen treatment modality.
      Optimal treatment algorithm is worked out. The expediency of conservative ulcer
      bleeding treatment, including primary and repeated endoscopic hemostasis, is
      proved. It allows performing deferred planned reconstructive operations, thus
      decreasing the operative risk substantially. Indications for the operative
      treatment of ulcer bleeding are specified, as well as efficacy and safety of
      organ-saving methods is proved.

PMID- 19156075
TI  - [Total endoprosthetic hip replacement in patients with protrusive acetabulum
      bottom defect].
AB  - Total endoprosthetic hip replacement was performed in 39 patients with femoral
      head protrusion. The necessity of acetabulum defect infilling is proved. For the
      purpose of it the ground allobone transplant was impacted using the originally
      constructed impactor. The maximal volume of bone transplant was 170sm3.
      Reconstruction of the rotation center was achieved in 82% cases. 18% failed to
      reconstruct the anatomic rotation center, though without the significant limb
      contraction. The functional result was evaluated according to Harrison's scale
      after 6-48 months after the operation.87,2% of patients demonstrated good and
      12,8% - satisfactory results in a 6 months period. There were no negative results
      in the group.

PMID- 19156076
TI  - [Treatment of pancreas injuries].
AB  - The treatment results of 189 patients with trauma of the pancreas are described.
      The rate of complications was 20,6%, the majority of them (69%) was due to
      traumatic pancreatoonecrosis progression. 45 (23,8%) of the injured had died.
      Abdominization of the pancreas and and programmed sanative bursoomentoscopy allow
      avoiding complications of the traumatic pancreatonecrosis.

PMID- 19156077
TI  - [Distal reconstructions under critical lower limb ischemia in elderly patients].
AB  - Performong reconstructive operations on arteriae is the only way to avoid limb
      amputation in patients with critical limb ischemia. Whereas reconstructive
      manipulations on distal arteriae, especially in patients older then 75 years, are
      often entailed by thrombotic complications. High peripheric vessel resistance is
      considered to be the crucial factor of the bypass thrombosis. The conducted study
      demonstrated the efficacy of the use of vena saphena magna collateral tributaries
      as bypass unload collectors. Femoral distal autovenous in situ reconstruction
      decreases vessel resistance. Due to the arterial reconstruction with bypass
      unload using unligated autovenous tributaries the cumulative bypass patency was
      75,1% a year after the procedure. 5-year cumulative bypass patency was 53,8%. 5 -
      year lethality was 28,6%.

PMID- 19156078
TI  - [Antioxidant activity and functional endothelium characteristics before and after
      the operation in patients with atherosclerosis obliterans].
AB  - Data of 410 male patients operated on account of atherosclerosis obliterans of
      lower limbs vessels. Biochemichal parameters of functional endothelium status of
      the arteriae after operative treatment are studied. Superoxide dismutase activity
      and nitric oxide level are registered before and 5 days after the operation.
      Statistically reliable changes of the biochemical parameters in dependence of
      methods of the operative treatment are determined.

PMID- 19156079
TI  - [The role of contrast enhancement in the computed tomography for pancreas cancer
      diagnostics].
AB  - Data of abdominal CT scan of 33 patients with morphologically verified cancer of
      the pancreas are analyzed. Advantages of bolus contrast enhancement for the CT
      diagnostics of pancreatic cancer are proved. Low diagnostic value of manual
      contrast injection in comparison with its bolus introduction is stated. Pancreas
      cancer can not be detected in 64% of patients at the native CT scanning, and in
      58% at the deferred phase of contrast excretion. Whereas only 6 and 9% of cases
      fail to prove the disease at arterial and portal contrast excretion phases,
      correspondingly. Thus, execution of the wrong modality of CT scanning and method
      of contrast introduction leads to misdiagnosis of the disease.

PMID- 19156080
TI  - [Pathology of the thyroid gland and multiple sclerosis: a possible influence on
      efficacy and tolerability of treatment].
AB  - This paper reviews the literature and own data on prevalence of thyroid diseases
      in patients with multiple sclerosis (MS). It has been shown that 20-25% of
      untreated MS patients have autoimmune thyroiditis (AIT) and/or subclinical
      hypothyroidism. No correlation was found between age, gender, disease course, MS
      duration, disability status and prevalence of thyroid disorders. Disease
      modifying therapy (DMT) of MS can induce or worsen the thyroid pathology. Female
      gender, pre-existing AIT, family history of thyroid disorders are considered as
      risk factors of thyroid dysfunction and autoimmunity during interferon- (IFN- )
      therapy. Most cases of autoimmune hyperthyroidism require discontinuation of IFN-
      therapy. The present study of thyroid status includes 43 MS patients, 42% of them
      with thyroid disorders such as thyroid nodes and subclinical hypothyroidism.
      Thyroid dysfunction is revealed mostly in patients treated with IFN- -1b; thyroid
      notes - in MS patients receiving copaxone. These facts emphasize the significance
      of systematic thyroid assessment in patients with MS especially during the long
      term DMT.

PMID- 19156081
TI  - [Correlations between clinical and immunological parameters in endogenous
      psychoses with a first episode at the juvenile age].
AB  - Sixty-seven patients, aged 16-25 years, with the first episode of endogenous
      psychosis (ICD-10 items F20.03, F20.23, F25) have been examined. Positive,
      negative and general psychopathological symptoms were assessed with the PANSS.
      Activities of leukocyte elastase (LE) and alpha1-proteinase inhibitor were used
      for measuring of innate immunity and the level of autoantibodies to nerve growth
      factor (Aab-NGF) was used for measuring of adaptive immunity. The manifestation
      of endogenous psychosis was accompanied by the activation of innate immunity, the
      level of activation was not related with the syndrome structure of episode (the
      prevalence of catatonic, hallucinatory-delusional or affective-delusional
      symptoms). The LE activity and dynamics of Aab-NGF during the treatment may be
      considered as prognostic markers of treatment effectiveness: the higher LE
      activity during the episode and decrease of Aab-NGF in the treatment process may
      predict a favorable therapeutic response.

PMID- 19156082
TI  - [Effectiveness of cerebrolysin in hypertensive supratentorial intracranial
      hemorrhages: results of a randomized triple blind placebo-controled study].
AB  - Cerebrolysin was administered to 38 patients with small hypertensive
      supratentorial intracranial hemorrhages. Cerebrolysin was used intravenous in
      drops in dosage of 30 ml during 14 days. High effectiveness and good tolerability
      of the treatment was shown. In the end of treatment, groups receiving
      cerebrolysin or placebo were statistically significant differed by the total
      NIHSS score, Bartel index and the Rankin's modified scale. Moreover, a trend to
      the decrease of intracranial hemorrhage volume was observed in patients treated
      with cerebrolysin.

PMID- 19156083
TI  - [Rehabilitation treatment of patients with children cerebral palsy using
      functional muscle electrostimulation during gait].
AB  - A technique for investigation of biomechanical and electromyographic parameters
      of gait in patients with diplegic form of children cerebral palsy (CCP) was
      described. Peculiarities of biomechanical and innervation structure of locomotor
      act in such patients were found. Recommendations for muscle electrostimulation
      during gait were specified. The best therapeutic effect was achieved in the
      combined four-channel electrostimulation of gluteus maximus muscles in the first
      half of support phase and of anterior tibial muscles in the end of the support
      phase and during the transfer phase. The muscle electrostimulation during gait
      demonstrated a positive effect of the treatment on the process of movement
      rehabilitation of CCP patients with diplegic form.

PMID- 19156084
TI  - [Dynamic stabilometry as a monitoring of movement and coordination disorders in
      the rehabilitation of patients with multiple sclerosis].
AB  - Disorders of movement and coordination are the most frequent and debilitating
      symptoms of multiple sclerosis. It has been shown that distinct changes of
      balance support are typical of the disease. This report includes an analysis of
      preliminary positive results of the use of stabilometry and biological feedback
      for the correction of balance in multiple sclerosis. A test "balance" has been
      used at baseline of the stabilometric study. After the rehabilitation, the
      positive changes of balance maintenance were seen in patients with low disability
      (EDSS<3,5). This test may be used as a measure of rehabilitation effectiveness.
      The results of the study may provide further determination of the approaches to
      the development of rehabilitation stabilometric algorithms.

PMID- 19156085
TI  - [Omaron in the treatment of vertebrobasilar insufficiency].
AB  - The study aimed at evaluation of tolerability, safety and clinical efficacy of
      omaron in the treatment of vertebrobasilar insufficiency (VBI). Forty patients
      with different stages of VBI have been examined. A diagnosis of VBI was based on
      the results of neurological study, ultrasonic dopplerography,
      electroencephalography, electrocardiography, brain MRI and CT examination.
      Neurological scales were used for assessment of neurological status and further
      data processing. The treatment with omaron resulted in significant clinical
      improvement and stabilization of the pathological process. The drug is well
      tolerated by patients including those of older age groups.

PMID- 19156086
TI  - [The use of lidocaine-coated plates (versatis) in the treatment of back pain].
AB  - Sixty patients with chronic vertebrogenic lumbalgia or lumboischialgia with
      exacerbation for at least 1 month were included in the study. A main group
      consisted of 40 patients and a control group of 20 patients. All patients took
      diclofenac in dosage 100 mg per day from the 1st day. Versatis was prescribed to
      patients of the main group from the 6th day. One-three plates were applied to the
      most painful spine areas and low extremities for 12 h during 5 days. To assess
      treatment efficacy, scales for measuring back pain, vertebral syndrome,
      neuropathic pain (NPS) as well as the Global Impression scale (CGI) and quality
      of life (EQ-5D) were used. A significant clinical effect was observed in 63% of
      patients of the main group: the additional reduction of pain by about a quarter,
      decrease of vertebral syndrome intensity, improvement of functional activity -
      spinal flexion-extension, ability to standing and quality of life. The NPS
      revealed that the use of versatis resulted in the significant decrease of
      "neuropathic" characteristics of pain; this effect remained after the end of
      treatment. The anesthetic effect of plates emerged in 1,2+/-1,1h after
      application, reached the maximum after 3,8+/-2,0 h, and continued during 4,7+/
      2,2 h after removing the plates from the skin. The safety of lidocaine-coated
      plates was observed.

PMID- 19156087
TI  - [Direct switch from conventional levodopa to stalevo
      (levodopa/carbidopa/entacapone) improves quality of life in Parkinson's disease:
      results of an open-label clinical study].
AB  - The most effective symptomatic treatment for Parkinson's disease (PD) is
      levodopa/dopa decarboxylase (DDC)-inhibitor or conventional levodopa. However,
      after a few years of treatment, motor complications may develop, such as
      <<wearing-off>> and dyskinesias. Symptoms of <<wearing-off>> can be both motor
      symptoms, e.g. tremor and bradykinesia, as well as non-motor symptoms (pain, mood
      changes and anxiety). The development of these complications may affect the
      patients quality of life (QOL). To investigate the efficacy and safety direct
      switch from conventional levodopa to stalevo(levodopa/carbidopa/entacapone) in PD
      patients with fluctuations and dyskinesias. METHODS/PATIENTS: Thirty four
      patients with PD were recruited in the study. The mean age (+/-SD) of the
      patients was 64,5+/-8,3 years, the mean duration of PD (+/-SD) was 5,9+/-3,1
      years, the mean H&Y was 2,5+/-0,5. All patients experienced fluctuations and six
      had dyskinesias (one patient had biphasic dyskinesias with painful dystonia). The
      mean baseline levodopa dose was 785,8+/-150,2 mg per day taking in three to six
      doses. Assessments were performed before, end of 1, 4 and 12 weeks of treatment
      period and consisted of Hoen/Yahr stages (H&Y), II and III parts of the Unified
      Parkinson's Disease Rating Scale (UPDRS), patients diaries with registration <<on
      off>> periods, scale EQ-5D, WOQ-9. While switching from conventional levodopa to
      stalevo taking single levodopa doses were equivalent or less. Maximum allowed
      doses of stalevo were four times per day. RESULTS: Direct switch to stalevo
      results in improvement of motor and non-motor symptoms (pain and anxiety) in
      fluctuating patients and significant prolongation of <<on>> periods (p<0.01). We
      observed dramatic improvement biphasic dyskinesias with painful dystonia and
      reducing severity of dyskinesias in others patients. Improvement was seen in QOL
      by scale EQ-5D from 10,7+/-1,9 to 8,6+/-2,1 points (p<0,05). Conclusions.
      Switching from conventional levodopa to stalevo is efficacy and safety and can
      significantly improve QOL PD patients with fluctuations and dyskinesias.

PMID- 19156088
TI  - [The role of rivastigmine (exelon) in the treatment of consequences of cranial
      brain trauma].
AB  - The use of rivastigmine in the rehabilitation of patients with cognitive
      disturbances after cranial-brain trauma (CBT) is reviewed. Replacement of
      cholinergic deficit exerts a positive effect on sanogenetic process in the brain,
      facilitate consolidation and learning of afferent information in the restoring
      brain. The authors emphasize that the administration of neuromediator
      preparations needs the level of organization of integrative brain activity which
      is sufficient for the formation of awakening reaction (opening of eyes -
      awakening from coma). It is suggested that neuromediator preparations, in
      particular cholinesterase inhibitor rivastigmine, should be used after the
      acutest CBT period, i.e. at least 2-3 weeks after CBT, when the main acute
      processes have been stabilized.

PMID- 19156089
TI  - [The association of the SNAP-25 gene polymorphism with verbal memory and
      attention in patients with major psychosis and healthy people].
AB  - The synaptosomal-associated protein (SNAP-25) plays an integral role in synaptic
      transmission and in memory consolidation in the hippocampus. Recently an
      association between SNAP-25 gene polymorphism and cognitive ability has been
      reported in two independent studies of healthy people and patients with
      schizophrenia. Authors carried out an association study of MnlI SNAP-25
      polymorphism and performance on neurocognitive tests measuring verbal memory,
      attention/executive functions in 66 patients with major psychosis, 75 their
      relatives and 136 controls. MANCOVA revealed a significant effect of group (small
      er, Cyrillic=0,00001) and genotype (small er, Cyrillic=0,012) as well as an
      interaction effect between group and genotype (small er, Cyrillic=0,02) on the
      performance on neurocognitive tests. Carriers of the TT genotype performed worse
      on the most tasks compared to other genotypes. The similar character of the MnlI
      SNAP-25 polymorphism effect on the variability of neurocognitive traits in all
      groups suggests the relationship between this gene and general cognitive ability.

PMID- 19156090
TI  - [Ultrasound evaluation of traumatic process course after endoscopic operations
      for pyoinflammatory diseases of soft tissues].
AB  - Soft tissues dynamic ultrasound investigation was applied for diagnostics of
      pyoinflammatory diseases. Ultrasound image correlated with intermuscular liquid
      formations (abscess, phlegmon) of soft tissues was revealed in 65 observations
      (100%). On the basis of findings 21 (32.3%) patients underwent surgical treatment
      of leg and gluteal region phlegmons and abscesses with application of traditional
      methods. Endoscopic operations on account of pyoinflammatory diseases of soft
      tissues were carried out in 44 (67.7%) patients. Ultrasound monitoring of
      traumatic process course was conducted. It is ascertained that total regress of
      purulent process occurs by the 14th day of postoperative period. Traumatic
      process regresses more rapid after endoscopic operations in comparison with
      traditional open methods.

PMID- 19156091
TI  - [Clinical course, diagnostics and treatment of periappendiceal mass].
AB  - 103 patients with appendix masses and periappendiceal abscesses were observed.
      The mean age of the patients was 47 years. Diagnostic algorithm included
      clinicolaboratoty investigations, X-ray examination of abdomen, ultrasound
      dynamic study and computed tomography. Method of direct endolymphatic
      administration of antibacterial drugs was applied in complex treatment of
      appendix mass in 25 patients. Involution of the infiltration was observed from
      the 4th day in this group of patients. Conservative treatment was efficacious in
      70 patients. Lancing of periappendical abscess was carried out to 29 patients.
      Puncture and drainage under ultrasound control--in 4 patients. There were no
      lethal outcomes.

PMID- 19156092
TI  - [Clinical course and surgical treatment of acute appendicitis in HIV-infected
      patients].
AB  - 197 patients with acute appendicitis were observed. HIV-infection was diagnosed
      in 82 (42%) patients. 115 (58%) patients without HIV-infection formed the
      comparison group. Patients with HIV-infection were arranged in the following way:
      II B stage--65 (79%) patients, II C stage--7 (8.5%), III A stage--6 (7.5%), III B
      stage (AIDS)--4 (5%). Annual increase of appendectomies in HIV patients is
      observed. Amount of patients with more serious stages of HIV infection also
      increases resulting from time factor of the disease.

PMID- 19156093
TI  - [False arterial aneurysms of celiac trunk system in patients with chronic
      pancreatitis].
AB  - 20 patients with chronic pancreatitis complicated by development of false
      aneurysms of arteries in celiac trunk system were observed. Diagnostics utilities
      included ultrasound study, contrasted computed tomography and angiography. Two
      types of aneurysms are distinguished: parencchymal and pseudocysts.
      Radioendovascular operation is the method of choice for aneurism treatment.
      Surgical treatment is carried out in case of aneurism rupture with voluminous
      bleeding or on necessity of elimination other complications of chronic
      pancreatitis (pseudocyst, pancreatic hypertension, wirsungolithiasis).

PMID- 19156094
TI  - [Clinicopathologic basis of ozonomagnetophoresis in treatment of festering
      wounds].
AB  - Results of treatment of 60 patients with festering wounds were comparatively
      studeid. According to the mode of local treatment the patients were divided into
      2 groups: wound irrigation with ozone was carried out in the first group; in the
      second group local ozone therapy was carried out in combination with low
      frequency magnetic fields--ozonomagnetophoresis. Bactericidal effect and
      antibiotic susceptibility of microflora is more marked using
      ozonomagnetophoresis. Tendency to purulo-necrotic tissue rejection from wound
      surface, regress of inflammation exudative stage with natural forming of
      granulation tissue in relatively short terms, its accelerated maturing and
      reparation are histologicaly marked.

PMID- 19156095
TI  - [Prolonged pulmonary ventilation in critically ill patients].
AB  - Treatment results of 336 patients in critical state who had required prolonged (3
      115 days) artificial pulmonary ventilation were analyzed. 3 groups were defined:
      98 patients with complications after operations on thoracic and abdominal organs
      and organ failure development; 55 patients with surgical infection and sepsis;
      183 patients with extensive burning injury III AB-IV degrees. Particular features
      of prolonged artificial pulmonary ventilation were studied. Optimum modes of
      respiratory therapy were determined. Frequency of complications was controlled.

PMID- 19156096
TI  - [Choice of treatment mode in planned inguinal canal plasty].
AB  - The mainstay of inguinal hernias surgical treatment is posterior wall of inguinal
      canal plasty. On the basis of extensive clinical material individual approach to
      the choice of inguinal canal plasty mode was worked out taking into account the
      age of the patient and degree of posterior wall destruction. Results of 1506
      planned herniotomies (867 single-layer plasties, 398 Shouldice multi-layer
      plasties, 162 Lichtenstein plasties) were evaluated. The choice of the optimal
      method of posterior wall reconstruction in every specific case allowed to improve
      the results of treatment noticeably, reducing the frequency of relapses to less
      than 1%.

PMID- 19156097
TI  - [Asymmetric excision in treatment of epithelial coccygeal duct].
AB  - Results of treatment of 96 patients with chronic fistulous form of coccygeal duct
      were studied. 42 patients were treated using modified Bascom method (surgical
      technique is described) formed the main group. 56 patients were operated on using
      traditional method of coccygeal duct excision and wound closure formed the
      control group. Pyoinflammatory wound complications were observed in 9 (16.7%)
      patients from the control group and in 2 (4.7%) patients from the main group.
      Duration of wound healing averaged 26.4 days in the control group, 13.4 days--in
      the main group. Coccygeal duct relapse was observed in 6 (11.1%) patients from
      the control group, in 1 (2.3%) patient from the main group. The modified Bascom
      technique for coccygeal duct treatment showed certain advantages in cases with
      unfavourable anatomic features of sacrococcygeal region.

PMID- 19156098
TI  - [Nickelid titanium implants biocompatibility evaluation in animal experiment].
AB  - In experiment on 15 rabbits it was shown that the highest biocompatibility in
      living organism was demonstrated by implants with modified by molybdenum-ions
      surface. The least corrosion stable there were the implants from alloy VT-8.
      Surface modification by silver-ions exerted depressive action upon red bone
      marrow producing its fatty degeneration.

PMID- 19156099
TI  - [Masticatory loading influence upon dental pulp functional status and its blood
      supply].
AB  - By pheodentography and Doppler laser flowmetry in 53 volunteers with clinically
      healthy parodontal tissues or parodontitis of light degree the masticatory teeth
      dental pulp functional status and its blood supply including microcirculation was
      studied. It was established that in case of one-sided type of chewing masticatory
      loading reduction on nonworking side increased vessel's tonus and capillary blood
      flow level. In case of regular use of chewing gum and filbert nuts
      vasoconstriction was developed, blood supply was considerably reduced and
      capillary blood flow level in the pulp was sharply increased that made up its
      functional adaptive mechanism of defense for the provision of plastic odontoblast
      function.

PMID- 19156100
TI  - [Clinical-physiological substantiation of brown algae preparation use for
      gingivitis treatment].
AB  - 1% water solution extract Fucus reduced inflammation emerged in cases of chronic
      parodontal disease. This was confirmed by positive dynamics of subjective and
      objective clinical symptoms, reduction of parodontal and hygienic indexes,
      improvement of parodontal microcirculation.

PMID- 19156101
TI  - [Study on the oral hygiene of patients with oral cavity cancer].
AB  - Many authors consider oral hygiene an important factor in the etiology and
      pathogenesis of oral cavity cancer. The aim of the present study was to establish
      the role of poor oral hygiene in the development of malignant lesions in the oral
      cavity. One hundred and three patients were interviewed. Questions, regarding
      oral hygiene were included in the interview. Results showed that 53,80% of urban
      residents brush their teeth twice daily whereas 65,52% of rural residents brush
      their teeth irregularly - p<0,001 (chi(2)=23,67). 46,88% of women clean their
      teeth twice daily. 46,94% of men do not maintain adequate oral hygiene - p<0,05
      (chi(2)= 9,21). Regarding the brush, it was found out that 56,00% of females use
      a hard bristle toothbrush, the same refers to 28,04% of men - p<0,05 (chi(2)=
      4,15). Hard bristle toothbrush was used by 48,88% of urban residents and 9,09% of
      rural residents - p<0,05 (chi(2)= 5,78). People up to 30 years of age use hard
      bristle toothbrush most often -39,13% - p<0,01 (chi(2)=12,26). The accumulated
      evidence provides further explanation why oral cavity cancer is more frequent in
      men, rural residents and in the elderly. Oral hygiene is a factor in the
      development of oral cavity cancer.

PMID- 19156102
TI  - [Application of medical ozone in endodontic practice].
AB  - We analyzed the results of comparative analysis of antimicrobial activity of
      ozone-oxygen mixture with various concentrations of ozone referring to strains of
      St. mutans, St. aureus, and also mixed cultivation from root follicle with a
      chronic periodontitis.

PMID- 19156103
TI  - [Photophoresis and mesophotophoresis of angioprotectant group preparations for
      comprehensive treatment of patients with chronic generalized parodontitis].
AB  - Examination of 118 patients with chronic generalized parodontitis of medium and
      heavy severity was performed and treatment was elaborated with the use of laser
      therapy and angioprotectants' photophoresis and mesophotophoresis. Use of the
      mentioned physical and physical-pharmacological methods in comprehensive cure let
      to shorten the course of treatment and increase remission duration.

PMID- 19156104
TI  - [Improved method of operative treatment of trigeminal neuralgia].
AB  - In 93 patients being treated in maxillofacial surgery unit partial removal of
      trigeminus with vessels; in 92 patients the operation was followed by
      simultaneous decortication of the foramen walls or partial decortication of the
      mandibular canal with simultaneous blocking of them by autografts. This method
      proved to be perspective and reliable inasmuch as after such operations paroxysm
      of pain were put an end to for the period of time from 2 to 8.6 years.

PMID- 19156105
TI  - [Microcirculation changes after polarized polychromatic light use in preoperative
      period in cases of face cosmetic operations].
AB  - Action of polarized polychromatic light used in preoperative period in cases of
      face cosmetic operations was studied upon microcirculatory bed status in
      operative zone. Morphometry showed that number of vessels in vision field in
      patients of the study group came to 173% of the such in the control group,
      vessel's area - 251% of the such in the control group. The data received
      confirmed that polarized polychromatic light use in preoperative period is
      effective method to improve microcirculatory bed status in operative zone.

PMID- 19156106
TI  - [Polioxidonium in comprehensive therapy of recurrent herpetic stomatitis in
      children with allergic diseases].
AB  - In the study with participation of 96 children of 1-7 years age with recurrent
      herpetic stomatitis and allergic diseases therapeutic efficacy of Polioxidonium
      was investigated. Polioxidonium was used in combination with traditional methods
      and with He-Ne-laser irradiation. Local oral cavity immunity, indexes of cellular
      immunity (in the reaction of lymphocytes blast-transformation with
      phytohemagglutinin), indexes of humoral immunity (IgG and IgE) were studied,
      complement C(3)-component was determined. Polioxidonium in combination with
      traditional methods and with laser therapy for recurrent herpetic stomatitis
      treatment in children with allergic diseases influenced favourably upon clinical
      course of allergic diseases, let achieve stable remission, increased efficacy of
      their treatment, promoted immunological status and shorten the terms of medical
      rehabilitation.

PMID- 19156107
TI  - [Occlusal caries of permanent molars of children - role of occlusal morphology].
AB  - In transversal epidemiologic study of 960 children of the age 7-14 years dynamics
      of occlusal caries in permanent molars depending on the occlusal morphology was
      established. The diagnostic scale of Espelid et al. was used to diagnose occlusal
      caries and the classification of Hirano and Aoba was used in the analysis of
      occlusal morphology. The results of the study showed that with age the share of
      occlusal surfaces of caries is increasing, the share of deep fissures is
      decreasing and the share of shallow fissures in first and second permanent molars
      remains unchanged. Occlusal morphology should be taken into consideration when
      elaborating a strategy for prevention of occlusal caries in children.

PMID- 19156108
TI  - [Fluoride in children saliva with its natural low intake in cases of fluoridated
      salt or water consumption].
AB  - Fluoride content dynamics in whole saliva in 3 groups of 5-6 year old children
      before and after meal. All children lived in the region with lov F-0,2 ppm in
      water, used fluoridated toothpaste and went to kindergartens. Children from group
      A (n=10) did not have other sources of F, group B children (n=10) drink one glass
      a day of F-water (1 ppm), participants from group C (n=11) eat F-salt 250+/-100
      ppm. The F in saliva samples gathered prior to and following meal was determined.
      Before the meal children saliva in group A contains 0,058 ppm F, in group B -
      0,078 ppm F, in group C - 0,074 ppm F. Saliva of group A children shows the
      increase of F after the meal (0,067 ppm), F decreases lower the starting point
      after the 5th minute (0,056 ppm) and restores to normal by minute 40. Group B
      showed the decrease of F right after the meal, lasting to minute 20 (0,060 ppm),
      than a small increase followed (0,063 ppm), and finally the restoration to normal
      by minute 50. In group C immediate raise of F (0,085 ppm) was noticed, by minute
      10 - some decline (0,076 ppm), from minute 20 F rises to level 0,090 ppm, after
      that it is decreasing slowly, but by minute 60 remains higher tan the starting
      point (0, 076 ppm). Thus, F-salt use allows to raise a basic level of F, and also
      to positively change F dynamics in oral fluid during the risk period (after the
      meal intake).

PMID- 19156109
TI  - [A method for the combined treatment of chronic cystic sinusitis].
AB  - A pathogenetically substantiated method is proposed for the combined treatment of
      chronic cystic sinusitis that includes sparing surgical intervention and
      postoperative treatment with ximedone, a regenerator drug with immunotropic
      activity.

PMID- 19156110
TI  - [Dependence of the physiological nasal cycle on the activity of mucociliary
      transport of paranasal sinus mucosa].
AB  - The endoscopic technique was used to manage bilateral isolated cystic sinusitis
      in 40 patients. Thirty two and eight patients underwent surgery on maxillary and
      sphenoidal sinuses respectively. Mucociliary transport in mucosal blood flow and
      confluence of sinuses were monitored intraoperatively. The physiological nasal
      cycle was fixed prior to surgery. Active mucociliary transport (MCT) was observed
      in maxillary and sphenoidal sinuses at the side of nasal cycle vasoconstriction.
      In all the patients natural anastomoses between sinuses were widely open; the
      patients differed in terms of the structure of osteomeatal complex and posterior
      cells of the ethmoidal labyrinth. Pathomorphological studies revealed pseudocysts
      in 90% of the patients. Envelopes of pseudocysts showed signs of chronic
      inflammation with immunologically governed alteration that is believed to be
      responsible for the large duration of the inflammatory process.

PMID- 19156111
TI  - [Experimental morphological substantiation of the surgical treatment of paranasal
      sinuses].
AB  - This experimental morphological study conducted on the rabbit model has
      demonstrated that the use of a modified trocar with "buried facets" for maxillary
      microsinusotomy allowed surgical trauma to be substantially reduced compared with
      the traditional approach. With the new instrument, the volume of hemorrhage was
      lower and the inflammatory reaction weaker while large necrotic zones with
      leukocytic infiltration were virtually absent. As a result, reparative processes
      developed faster and healing took less time. No complications could be documents
      (e.g. nonclosure of the defect, formation of cartilaginous tissue instead of
      bone, and/or transition of acute inflammation into a chronic process).

PMID- 19156112
TI  - [Certain specific features of the structure and vegetative innervation of the
      soft palate in patients with nasal obstruction and snoring].
AB  - Fifty patients presenting with night snore were examined for neck anthropometry,
      evaluation of the state of nasal cavity and vegetative homeostasis. Fourteen
      patients were given combined surgical treatment including endonasal functional
      operation and radiofrequency-assisted uvuloplasty. Concomitant biopsy provided
      materials for histochemical characteristic of nerve structures in the soft
      palatal tissue.

PMID- 19156113
TI  - [The role of neurovegetative disturbances in the clinical picture and treatment
      of vasomotor rhinitis].
AB  - Sixty four patients of different age groups having vasomotor rhinitis underwent
      submucous vasotomy of inferior nasal turbinates combined with mucosal biopsy.
      Neuromorphological studies have demonstrated mucosal desympathization especially
      pronounced in the patients aged between 51 and 70 years. Comparative evaluation
      of the efficacy of surgical and conservative (dimephosphon therapy) treatment of
      vasomotor rhinitis was conducted.

PMID- 19156114
TI  - [Superior laryngeal nerve neuropathy].
AB  - Clinical examination of 28 patients with superior laryngeal nerve neuropathy
      along with X-ray and electromyographic studies has demonstrated that the disease
      was associated with cervical spine osteochondrosis. The latter condition was
      responsible for myofixation, conjugation of laryngeal ligaments and fascii that
      resulted in the compression of superior laryngeal nerve.

PMID- 19156115
TI  - [Stages of introduction of endonasal microendoscopic dacryocystorhinostomy into
      ophthalmological clinical practice].
AB  - Endonasal microendoscopic dacryocystorhinostomy has a number of important
      advantages over external dacryocystorhinostomy and needs to be introduced into
      routine practical work of all ophthalmological clinics having a dacryiologist on
      the staff. At the initial stage of mastering of the endonasal technique,
      cooperation between health-care professionals representing different disciplines,
      e.g. rhinologist and ophthalmologist, is of importance to ensure differential
      diagnosis of concomitant nasal pathologies and treatment of the affected
      nasolacrimal passages. At later stages, patients with lacrimal problems should be
      placed under the supervision of a dacryologist well trained in different surgical
      procedures and having an excellent knowledge of anatomical structure and
      physiological functions of the lacrimal apparatus as well as good understanding
      of mechanisms underlying its pathology.

PMID- 19156116
TI  - [Clinical application of a modified trocar for the treatment of maxillary sinus
      pathology].
AB  - A new instrument has been developed to facilitate access into a maxillary sinus
      for the purpose of diagnostic endoscopy and adequate surgical sanation. The
      cannula of this trocar has a proximal coniform portion and a distal cylindrical
      part with a lateral aperture and a fixing tip. Such design ensures perfect
      sanation of the maxillary sinus. The instrument has three stylets one of which
      (non-traumatic) makes possible the approach to the canine fossa and two others
      (having concave edges and shaping knife-like blades) to the maxillary sinus.
      These two stylets are used to gently cut the anterior wall of the sinus and
      obtain osteo-periosteal fragments in the form of three lobes. Maxillary
      microsinusotomy being completed, the lobes become spontaneously apposed which
      leads to rapid healing and formation of a soft scar along the section line as
      well as to complete restoration of the anterior wall of the maxillary sinus.
      Cannulas of two different diameters are available that enable the instrument to
      be used for the treatment of adults and children.

PMID- 19156117
TI  - [Experimental model for the evaluation of the method and regimen of inhalation
      therapy].
AB  - An experimental model of upper respiratory passages has been developed to be used
      for the choice of parameters of inhalation therapy for inflammatory processes in
      the larynx and evaluation of its efficiency. The model was employed to
      characterize "inhalation accessibility" of different segments of the upper
      respiratory passages and to determine the amount of a medicinal product to be
      delivered to the affected zone per unit time. Optimal parameters of the
      inhalation procedure have been derived.

PMID- 19156118
TI  - [Medicamentous test for the screening of pharmacogenic risk of aminoglycoside
      ototoxicity].
AB  - The primary objective of this work was to assess the informative value
      (sensitivity and specificity) of the diagnostic screening of subjects at high
      risk of aminoglycoside ototoxicity. The method is based on the vegetative
      resonance test. It is argued that this test meets the requirements to diagnostic
      screening procedures and allows for the evaluation of susceptibility to
      aminoglycosides from such phenotypic trait as responsiveness to resonance between
      oscillations of aminoglycosides and elongated cells in neuroepithelium of the
      acoustic analyzer. Sensitivity and specificity of the test was estimated to be 87
      and 94% respectively using the "nerve and cochlear duct" organopreparation and
      the parameter of "acquired toxic information".

PMID- 19156119
TI  - [Nonspecific pains and depression in neurology].
AB  - Nonspecific pains (NP) are considered as general symptoms in different
      pathologies. They occurred in most patients with depression. A data analysis
      using a program "PARUS" allowed to specify clinical characteristics related to
      depression. It has been found that the clinically significant depressive state
      amplified the pains characteristic of somatic and neurological pathology.
      Therefore, treatment of such patients must be complex and include a therapy of
      somatic disease and antidepressants. A choice of the latter is depended on its
      thymoanaleptic and, in case of NP, antinociceptive activity.

PMID- 19156120
TI  - [Clinical, neurophysiological and psychological characteristics of neurosis in
      patients with panic disorders].
AB  - Forty-eight patients with panic disorders (PD), aged 31,5 years, 17 men, 31
      women, were studied. The results were analyzed in comparison to a control group
      which comprised 16 healthy people, 6 men, 10 women, mean age 29,5 years. A
      traditional clinical approach, including somatic, neurologic and psychiatric
      examination, was used in the study. Also, a neurophysiological study using
      compression and spectral analyses, EEG, cognitive evoked potentials, skin evoked
      potentials, was conducted. A psychological examination included assessment of
      personality traits (Cattell's test), MMPI personality profile, mechanisms of
      psychological defense, the "Life style index" and Sondy test. A decrease of - and
      -rhythms was found that implied the reduction of activation processes. The
      psychological data mirror as common signs characteristic of all PD, as well as
      psychological features characteristic of neurotic disorders. The results obtained
      confirm the heterogeneity of PD in nosological aspect that demands using
      differential approach to the problems of their diagnostics and treatment.

PMID- 19156121
TI  - [Efficacy of memantine in Parkinson's disease with dementia].
AB  - Memantine (M) was used in the treatment of patients with Parkinson's disease (PD)
      with dementia. The drug was prescribed to 15 patients at first in a single dosage
      of 5 mg daily for one week, then the dosage was increased to 10 mg daily (one
      week), after to 15 mg daily (one week) and from the 4th week - to 20mg daily.
      Patients of the control group did not receive the drug. Efficacy and safety of M
      were assessed clinically and with a battery of widespread scales (UPDRS, MMSE,
      CGI etc), neuropsychological tests and the quality of life scale (PDQ-8). The
      study showed the ability of M to cause a stable improvement of mental state and
      its good tolerability. The efficacy of M in the cases studied was comparable with
      that in Alzheimer's disease.

PMID- 19156122
TI  - [Halidor in the treatment of cerebral vascular diseases in emergency cases].
AB  - An aim of the study was to assess efficacy and safety of an injection form of
      galidor (bencyclan) in patients with chronic cerebral vascular diseases in cases
      of emergency. Sixty patients with discirculatory encephalopathy (DE), including
      38 with basilar insufficiency, were treated. Mean age of patients was 59,7 years.
      Halidor was injected slowly intravenous in dosage 50 mg (13 patients) or 100 mg
      (56 patients) during 5 minutes. After treatment, the following symptoms were
      observed: sluggishness (2,8% of patients), excitement (0,9%), hyperhydrosis
      (0,9%), coordination disturbance (0,9%). Halidor does not cause side-effects and
      complications in 90% of patients. The results obtained suggest high efficacy of
      galidor in DE. A good effect has been achieved in 72,5% of cases, fair effect in
      20,3%, no effect has been found in 7,2%.

PMID- 19156123
TI  - [Psychotherapy of patients with personality disorders with predominance of
      hypochondria].
AB  - A standard of psychotherapeutic help to patients with hypochondriac disorder
      developed in paranoid, schizoid, anxiety and dependent personality disorders is
      worked out. In this case, hypochondria is inseparable from the personality
      structure. Patients of investigated group (61 people) received traditional
      medical treatment, individual differential symptomatic psychotherapy and a short
      group course with a variant of the therapy by means of creative sell-expression
      (TCSEB) worked out by M. Burno. This course aimed at preventing new hypochondriac
      symptoms and acquiring spiritual creative ways to overcome themselves. The
      control group (70 people) differed from the index-group by not receiving CSEB. A
      statistical analysis revealed a significant therapeutic efficacy of the mentioned
      new clinical psychotherapeutic standard compared to the psychotherapeutic tactics
      without TCSEB.

PMID- 19156124
TI  - [First generation antidepressants in the current treatment of depression].
AB  - An aim of the present retrospective (based on medical hystories) study, was to
      specify the choice of different antidepressants of first generations (AFG) by
      practical physicians for treatment of different types of depressions. Three
      hundreds and thirty-four cases (201 female, 133 male) have been studied. The
      sample included the following types of depression: vital (16 patients), anxious
      (64), hypochondriac (74), apathic (71), asthenic (13), anesthetic (17),
      anankastic (19), hysteric (51) and with somatic equivalents (9). It has been
      found that amitryptiline and imipramine are prescribed in the various depressive
      states, clomipramine is more often used in anankastic depressions and maprotiline
      - in anesthetic depressions. When choosing an antidepressant, practical
      physicians follow the current empiric scheme corresponding to general ideas on
      the correlation between psychopathological presentations and action of
      psychotropic drugs on the level of cell metabolism (deficit) of monoamines
      (dopamine, serotonin, noradrenalin). Moreover, physicians consider clomipramine
      and maprotiline as more selective antidepressants as they really are; the use of
      maprotiline is not enough. In conclusion, the author emphasizes the necessity of
      increasing the knowledge of physicians about possibilities of using AFG taking
      into account mechanisms of their action.

PMID- 19156125
TI  - [Peculiarities of the neurological status and electroencephalogram in operators
      of the control unit of nuclear power station].
AB  - One hundred and five operators of the control unit of the Kursk nuclear power
      station (NPS) have been studied: 45 people after the shift (main group) and 60 -
      in the day off. The shift was found to exert a significant influence on the
      functional state of the nervous system promoting the development or aggravation
      of autonomous dysfunction. In some cases, it causes an elevation of blood
      pressure to the level of risk for cerebral vascular disease. The effect of shift
      on the cerebral bioelectric activity of NPS operators manifests itself in the
      decrease of percentage of unchanged EEG, increase of alpha-rhythm spectral power
      density in the parietal leads and theta-rhythm in the posterior temporal and
      parietal leads. These changes may be caused by weariness as well as the effects
      of adverse factors the operators were exposed to at the NPS. The authors suggest
      to include the methods of evaluating of autonomous dysfunction and recording of
      alpha-rhythm spectral power density in the parietal leads and theta-rhythm in the
      posterior temporal and parietal leads in a special clinical examination of NPS
      operators.

PMID- 19156126
TI  - [Assessment of the brain functional state in pathological gamblers with a complex
      of neurophysiological methods].
AB  - A diagnosis of pathological gambling met ICD-10 and DSM-IV criteria. Based on the
      electroencephalographic data, two types of disturbances of electric activity were
      singled out: (1) abnormalities of amplitude and frequency characteristics of
      alpha-rhythm and (2) the disturbance of mechanisms of synchronized slow waves
      generating associated with the alpha-rhythm abnormalities. Despite the fact that
      patients did not abuse drugs, they had changes similar to those in drug addicts,
      i.e. the increase of index and power of beta-rhythm, abnormalities of amplitude
      and frequency characteristics of alpha-rhythm. Significant correlations between
      the level of impulsivity and the type of EEG parameters were found. The
      prolongation of latency of P300 auditory event-related potentials was correlated
      with the presence of EEG bilaterally synchronized waves of the theta-band that
      were recorded mostly in the frontal brain areas and with cognitive impairment.
      The results obtained suggest the dysfunction of brain diencephalic structures as
      well as medial-basal regions of frontal lobes that may cause predisposition to
      pathological gambling.

PMID- 19156127
TI  - Linear combinations of docking affinities explain quantitative differences in RTK
      signaling.
AB  - Receptor tyrosine kinases (RTKs) process extracellular cues by activating a broad
      array of signaling proteins. Paradoxically, they often use the same proteins to
      elicit diverse and even opposing phenotypic responses. Binary, 'on-off' wiring
      diagrams are therefore inadequate to explain their differences. Here, we show
      that when six diverse RTKs are placed in the same cellular background, they
      activate many of the same proteins, but to different quantitative degrees.
      Additionally, we find that the relative phosphorylation levels of upstream
      signaling proteins can be accurately predicted using linear models that rely on
      combinations of receptor-docking affinities and that the docking sites for
      phosphoinositide 3-kinase (PI3K) and Shc1 provide much of the predictive
      information. In contrast, we find that the phosphorylation levels of downstream
      proteins cannot be predicted using linear models. Taken together, these results
      show that information processing by RTKs can be segmented into discrete upstream
      and downstream steps, suggesting that the challenging task of constructing
      mathematical models of RTK signaling can be parsed into separate and more
      manageable layers.

PMID- 19156128
TI  - Cell cycle regulation by feed-forward loops coupling transcription and
      phosphorylation.
AB  - The eukaryotic cell cycle requires precise temporal coordination of the
      activities of hundreds of 'executor' proteins (EPs) involved in cell growth and
      division. Cyclin-dependent protein kinases (Cdks) play central roles in
      regulating the production, activation, inactivation and destruction of these EPs.
      From genome-scale data sets of budding yeast, we identify 126 EPs that are
      regulated by Cdk1 both through direct phosphorylation of the EP and through
      phosphorylation of the transcription factors that control expression of the EP,
      so that each of these EPs is regulated by a feed-forward loop (FFL) from Cdk1. By
      mathematical modelling, we show that such FFLs can activate EPs at different
      phases of the cell cycle depending of the effective signs (+ or -) of the
      regulatory steps of the FFL. We provide several case studies of EPs that are
      controlled by FFLs exactly as our models predict. The signal-transduction
      properties of FFLs allow one (or a few) Cdk signal(s) to drive a host of cell
      cycle responses in correct temporal sequence.

PMID- 19156129
TI  - An integrated workflow for charting the human interaction proteome: insights into
      the PP2A system.
AB  - Protein complexes represent major functional units for the execution of
      biological processes. Systematic affinity purification coupled with mass
      spectrometry (AP-MS) yielded a wealth of information on the compendium of protein
      complexes expressed in Saccharomyces cerevisiae. However, global AP-MS analysis
      of human protein complexes is hampered by the low throughput, sensitivity and
      data robustness of existing procedures, which limit its application for systems
      biology research. Here, we address these limitations by a novel integrated
      method, which we applied and benchmarked for the human protein phosphatase 2A
      system. We identified a total of 197 protein interactions with high
      reproducibility, showing the coexistence of distinct classes of phosphatase
      complexes that are linked to proteins implicated in mitosis, cell signalling, DNA
      damage control and more. These results show that the presented analytical process
      will substantially advance throughput and reproducibility in future systematic AP
      MS studies on human protein complexes.

PMID- 19156130
TI  - Dynamic map of protein interactions in the Escherichia coli chemotaxis pathway.
AB  - Protein-protein interactions play key roles in virtually all cellular processes,
      often forming complex regulatory networks. A powerful tool to study interactions
      in vivo is fluorescence resonance energy transfer (FRET), which is based on the
      distance-dependent energy transfer from an excited donor to an acceptor
      fluorophore. Here, we used FRET to systematically map all protein interactions in
      the chemotaxis signaling pathway in Escherichia coli, one of the most studied
      models of signal transduction, and to determine stimulation-induced changes in
      the pathway. Our FRET analysis identified 19 positive FRET pairs out of the 28
      possible protein combinations, with 9 pairs being responsive to chemotactic
      stimulation. Six stimulation-dependent and five stimulation-independent
      interactions were direct, whereas other interactions were apparently mediated by
      scaffolding proteins. Characterization of stimulation-induced responses revealed
      an additional regulation through activity dependence of interactions involving
      the adaptation enzyme CheB, and showed complex rearrangement of chemosensory
      receptors. Our study illustrates how FRET can be efficiently employed to study
      dynamic protein networks in vivo.

PMID- 19156132
TI  - How to deal with large models?

PMID- 19156131
TI  - Input-output behavior of ErbB signaling pathways as revealed by a mass action
      model trained against dynamic data.
AB  - The ErbB signaling pathways, which regulate diverse physiological responses such
      as cell survival, proliferation and motility, have been subjected to extensive
      molecular analysis. Nonetheless, it remains poorly understood how different
      ligands induce different responses and how this is affected by oncogenic
      mutations. To quantify signal flow through ErbB-activated pathways we have
      constructed, trained and analyzed a mass action model of immediate-early
      signaling involving ErbB1-4 receptors (EGFR, HER2/Neu2, ErbB3 and ErbB4), and the
      MAPK and PI3K/Akt cascades. We find that parameter sensitivity is strongly
      dependent on the feature (e.g. ERK or Akt activation) or condition (e.g. EGF or
      heregulin stimulation) under examination and that this context dependence is
      informative with respect to mechanisms of signal propagation. Modeling predicts
      log-linear amplification so that significant ERK and Akt activation is observed
      at ligand concentrations far below the K(d) for receptor binding. However, MAPK
      and Akt modules isolated from the ErbB model continue to exhibit switch-like
      responses. Thus, key system-wide features of ErbB signaling arise from nonlinear
      interaction among signaling elements, the properties of which appear quite
      different in context and in isolation.

PMID- 19156133
TI  - Asymmetric shorter-duplex siRNA structures trigger efficient gene silencing with
      reduced nonspecific effects.
AB  - Small interfering RNAs (siRNAs) are short, double-stranded RNAs that mediate
      efficient gene silencing in a sequence-specific manner by utilizing the
      endogenous RNA interference (RNAi) pathway. The current standard synthetic siRNA
      structure harbors a 19-base-pair duplex region with 3' overhangs of 2 nucleotides
      (the so-called 19+2 form). However, the synthetic 19+2 siRNA structure exhibits
      several sequence-independent, nonspecific effects, which has posed challenges to
      the development of RNAi therapeutics and specific silencing of genes in research.
      In this study, we report on the identification of truncated siRNA backbone
      structures with duplex regions shorter than 19 bp (referred to as asymmetric
      shorter-duplex siRNAs or asiRNAs) that can efficiently trigger gene silencing in
      human cell lines. Importantly, this asiRNA structure significantly reduces
      nonspecific effects triggered by conventional 19+2 siRNA scaffold, such as sense
      strand-mediated off-target gene silencing and saturation of the cellular RNAi
      machinery. Our results suggest that this asiRNA structure is an important
      alternative to conventional siRNAs for both functional genomics studies and
      therapeutic applications.

PMID- 19156134
TI  - Image-guided, lobe-specific hydrodynamic gene delivery to swine liver.
AB  - Image-guided, lobe-specific hydrodynamic gene delivery to liver was assessed in
      pigs. The procedure involved image-guided insertion of a balloon catheter to the
      hepatic vein of the selected lobe from the jugular vein and hydrodynamic
      injection of plasmid DNA using a newly developed computer-controlled injection
      device. We demonstrated that the impact of the procedure was regional with
      minimal effects on neighboring lobes. Level of gene expression resulted from the
      procedure was 10(7) relative light units (RLU)/mg in the targeted lobes and 10(2)
      10(5) RLU/mg in the nontargeted lobes 4 hours after hydrodynamic injection of
      pCMV-Luc plasmids. Occlusion of blood flow in the inferior vena cava (IVC) or IVC
      plus portal vein (PV) was effective in elevating hydrodynamic pressure in the
      targeted vasculature but did not enhance gene delivery efficiency. Physiological
      examination on pigs with IVC occlusion revealed transient decreases of blood
      pressure and respiration rate. Removal of occlusion from IVC resulted in a rapid
      and transient increase in heart rate. Occlusion of the PV and hepatic vein showed
      no effect on physiological and cardiac activities. No major changes in serum
      composition were observed. These results suggest that (i) image-guided, lobe
      specific hydrodynamic procedure is effective for regional gene delivery to liver,
      (ii) blockade in IVC should be avoided for hydrodynamic gene delivery to the
      liver, and (iii) clinical application of hydrodynamic gene delivery to liver is
      feasible.

PMID- 19156135
TI  - Biochemical correction of very long-chain acyl-CoA dehydrogenase deficiency
      following adeno-associated virus gene therapy.
AB  - We report the development of a gene replacement strategy for very long-chain acyl
      CoA dehydrogenase (VLCAD) deficiency. VLCAD is a mitochondrial enzyme involved in
      fatty acid beta-oxidation, a key step in energy production during times of
      fasting or stress. Deficiency of VLCAD classically presents as hepatic
      dysfunction, hypoglycemia, cardiomyopathy, rhabdomyolysis, and/or sudden death.
      While dietary therapy for VLCAD deficiency has proven beneficial in preventing
      some symptoms, a risk of metabolic catastrophic decompensation remains throughout
      life during times of increased energy demand. We designed a recombinant adeno
      associated virus (AAV) expressing the human VLCAD gene (AAV8-hVLCAD). To
      demonstrate its in vivo activity, AAV8-hVLCAD was administered via the tail vein
      to VLCAD-knockout mice. A reduction in accumulated serum long-chain
      acylcarnitines and increased fasting tolerance judged on blood glucose
      concentrations were observed as of 11 days postinjections through >100 days.
      Western analysis of liver, skeletal muscle, and heart extracts using PEP1 anti
      hVLCAD antibody revealed short-term hVLCAD expression in the liver and muscle and
      longer-term expression in heart. This demonstrates the ability of human VLCAD to
      correct the biochemical phenotype of VLCAD-deficient mice.

PMID- 19156136
TI  - HOX transcription factors are potential therapeutic targets in non-small-cell
      lung cancer (targeting HOX genes in lung cancer).
AB  - The HOX genes are a family of homeodomain-containing transcription factors that
      determine the identity of cells and tissues during embryonic development. They
      are also known to behave as oncogenes in some haematological malignancies. In
      this study, we show that the expression of many of the HOX genes is highly
      elevated in primary non-small-cell lung cancers (NSCLCs) and in the derived cell
      lines A549 and H23. Furthermore, blocking the activity of HOX proteins by
      interfering with their binding to the PBX co-factor causes these cells to undergo
      apoptosis in vitro and reduces the growth of A549 tumours in vivo. These findings
      suggest that the interaction between HOX and PBX proteins is a potential
      therapeutic target in NSCLC.

PMID- 19156137
TI  - DLEC1 is a functional 3p22.3 tumour suppressor silenced by promoter CpG
      methylation in colon and gastric cancers.
AB  - Promoter CpG methylation of tumour suppressor genes (TSGs) is an epigenetic
      biomarker for TSG identification and molecular diagnosis. We screened genome wide
      for novel methylated genes through methylation subtraction of a genetic
      demethylation model of colon cancer (double knockout of DNMT1 and DNMT3B in
      HCT116) and identified DLEC1 (Deleted in lung and oesophageal cancer 1), a major
      3p22.3 TSG, as one of the methylated targets. We further found that DLEC1 was
      downregulated or silenced in most colorectal and gastric cell lines due to
      promoter methylation, whereas broadly expressed in normal tissues including colon
      and stomach, and unmethylated in expressing cell lines and immortalised normal
      colon epithelial cells. DLEC1 expression was reactivated through pharmacologic or
      genetic demethylation, indicating a DNMT1/DNMT3B-mediated methylation silencing.
      Aberrant methylation was further detected in primary colorectal (10 out of 34,
      29%) and gastric tumours (30 out of 89, 34%), but seldom in paired normal colon
      (0 out of 17) and gastric (1 out of 20, 5%) samples. No correlation between DLEC1
      methylation and clinical parameters of gastric cancers was found. Ectopic
      expression of DLEC1 in silenced HCT116 and MKN45 cells strongly inhibited their
      clonogenicity. Thus, DLEC1 is a functional tumour suppressor, being frequently
      silenced by epigenetic mechanism in gastrointestinal tumours.

PMID- 19156138
TI  - Integrating BRAF/MEK inhibitors into combination therapy for melanoma.
AB  - The discovery of BRAF mutations in melanoma has not yet translated into clinical
      success, suggesting that BRAF/MEK inhibitors will need to be combined with other
      agents. In the current review, we discuss other pathways likely to be important
      for melanoma progression and suggest possible drug combinations for future
      clinical testing.

PMID- 19156139
TI  - Exemestane as primary treatment of oestrogen receptor-positive breast cancer in
      postmenopausal women: a phase II trial.
AB  - To assess the efficacy of exemestane as neoadjuvant treatment, 55 postmenopausal
      women (mean age: 76 years; range: 66-86) with oestrogen-positive non-metastatic
      breast tumour and ineligible for conservative surgery were recruited into this
      phase II trial to receive oral exemestane (25 mg day(-1)) for 6 months. Tumour
      response was evaluated by clinical examination, mammography and breast ultrasound
      every 2 months (RECIST criteria). Overall clinical response to treatment was
      observed in 33/54 patients (61.1%; 95% CI: 48.1-74.0). Radiological responses in
      45 evaluable patients were partial response in 23, stable disease in 21 and
      disease progression in one. Median time to surgery from the commencement of
      treatment was 7 months; conservative surgery in 24 patients (55.8%) and
      mastectomy in 19 patients (34.5%); no surgery (patient choice or considered not
      suitable by attending physician) in 12 patients. Pathologic complete response was
      observed in breast and axilla in one patient (2.3%) and different forms of
      persistent disease in 23 (53.5%) patients. Treatment tolerance was good. No
      patient withdrew from the study because of toxic events. We conclude that
      exemestane as a primary treatment is feasible and very active in elderly patients
      with large-sized breast cancer tumour. Conservative surgery is feasible in
      responding patients. No severe adverse events were detected. The optimal hormonal
      treatment schedule remains to be determined.

PMID- 19156140
TI  - Association between serum 25(OH)D and death from prostate cancer.
AB  - Based on observations that for certain cancers, mortality varies according to sun
      exposure, vitamin D has been proposed to influence on disease progression. This
      study aims to investigate whether serum levels of 25(OH)D are associated with
      prognosis in patients with prostate cancer. In total, 160 patients with a serum
      sample in the JANUS serum bank were included. For 123 patients a pre-treatment
      serum sample was taken, whereas 37 of the patients had received hormone therapy
      prior to the blood collection. The serum level of 25(OH)D was classified as low
      (<50 nmol l(-1)), medium (50-80 nmol l(-1)) or high (>80 nmol l(-1)). A Cox
      proportional hazard regression model was used to assess the association between
      serum 25(OH)D and cancer mortality. During follow-up, 61 deaths occurred, of whom
      52 died of prostate cancer. The median time of follow-up was 44.0 months (range,
      1.2-154.6). Serum 25(OH)D at medium or high levels were significantly related to
      better prognosis (RR 0.33; 95% CI 0.14-0.77, RR 0.16; 95% CI 0.05-0.43) compared
      with the low level. Analysis restricted to patients receiving hormone therapy
      gave a stronger association. The serum level of 25(OH)D may be involved in
      disease progression and is a potential marker of prognosis in patients with
      prostate cancer.

PMID- 19156141
TI  - BCRP expression does not result in resistance to STX140 in vivo, despite the
      increased expression of BCRP in A2780 cells in vitro after long-term STX140
      exposure.
AB  - The anti-proliferative and anti-angiogenic properties of the endogenous oestrogen
      metabolite, 2-methoxyoestradiol (2-MeOE2), are enhanced in a series of
      sulphamoylated derivatives of 2-MeOE2. To investigate possible mechanisms of
      resistance to these compounds, a cell line, A2780.140, eightfold less sensitive
      to the 3,17-O,O-bis-sulphamoylated derivative, STX140, was derived from the A2780
      ovarian cancer cell line by dose escalation. Other cell lines tested did not
      develop STX140 resistance. RT-PCR and immunoblot analysis demonstrated that
      breast cancer resistance protein (BCRP) expression is dramatically increased in
      A2780.140 cells. The cells are cross-resistant to the most structurally similar
      bis-sulphamates, and to BCRP substrates, mitoxantrone and doxorubicin; but they
      remain sensitive to taxol, an MDR1 substrate, and to all other sulphamates
      tested. Sensitivity can be restored using a BCRP inhibitor, and this pattern of
      resistance is also seen in a BCRP-expressing MCF-7-derived cell line, MCF-7.MR.
      In mice bearing wild-type (wt) and BCRP-expressing tumours on either flank, both
      STX140 and mitoxantrone inhibited the growth of the MCF-7wt xenografts, but only
      STX140 inhibited growth of the MCF-7.MR tumours. In conclusion, STX140, a
      promising orally bioavailable anti-cancer agent in pre-clinical development, is
      highly efficacious in BCRP-expressing xenografts. This is despite an increase in
      BCRP expression in A2780 cells in vitro after chronic dosing with STX140.

PMID- 19156142
TI  - Association of ERBB2 gene status with histopathological parameters and disease
      specific survival in gastric carcinoma patients.
AB  - The clinical significance of ERBB2 amplification/overexpression in gastric cancer
      remains unclear. In this study, we evaluated the ERBB2 status in 463 gastric
      carcinomas using immunohistochemistry (IHC) and fluorescence in situ
      hybridisation (FISH), and compared the findings with histopathological
      characteristics and with disease-specific survival. ERBB2 overexpression (2+ and
      3+) and amplification (ratio ERBB2/CEP17 >or= 2) were found in 43 (9.3%) and 38
      (8.2%) gastric carcinomas, respectively. Perfect IHC/FISH correlation was found
      for the 19 cases scored as 0 (all negative by FISH), and also for the 25 cases
      scored as 3+ (all positive by FISH). One out of six carcinomas scored as 1+ and
      12 out of 18 carcinomas scored as 2+ were positive by FISH. ERBB2 amplification
      was associated with gastric carcinomas of intestinal type (P=0.007) and with an
      expansive growth pattern (P=0.021). ERBB2 amplification was detected in both
      histological components of two mixed carcinomas, indicating a common clonal
      origin. A statistically significant association was found between ERBB2
      amplification and worse survival in patients with expansive gastric carcinomas
      (P=0.011). We conclude that ERBB2 status may have clinical significance in
      subsets of gastric cancer patients, and that further studies are warranted to
      evaluate whether patients whose gastric carcinomas present ERBB2
      amplification/overexpression may benefit from therapy targeting this surface
      receptor.

PMID- 19156143
TI  - Gonadal function in male patients after treatment for malignant lymphomas, with
      emphasis on chemotherapy.
AB  - Gonadal function was assessed in male lymphoma survivors based on serum hormone
      levels (LH, FSH, testosterone, SHBG), and was related to treatment, age and
      observation time. Male patients <or= 50 years at diagnosis treated for Hodgkin's
      (HL) and/or non-Hodgkin's lymphoma (NHL) at the Norwegian Radium Hospital from 1
      January 1980 to 31 December 2002 were included. Five treatment groups were
      defined: 1: radiotherapy only and/or low gonadotoxic chemotherapy (both HL and
      NHL)('No/low'), 2: medium gonadotoxicity chemotherapy for NHL ('med-NHL'), 3:
      medium gonadotoxicity chemotherapy for HL ('med-HL'), 4: highly gonadotoxic
      chemotherapy for NHL ('high-NHL'), 5: highly gonadotoxic chemotherapy for HL
      ('high-HL'). Gonadal hormone levels were categorised into three groups: 1: All
      gonadal hormones within normal range (normal), 2: Isolated elevated FSH, with LH,
      SHBG and testosterone within normal range (exocrine hypogonadism), 3:
      Testosterone below and/or LH above normal range (endocrine hypogonadism). One
      hundred and forty-four (49%) of the patients had normal gonadal hormones, 60
      (20%) displayed exocrine hypogonadism and almost one-third (n=90, 30%) had
      endocrine hypogonadism. Compared to those treated with no/low gonadotoxic
      chemotherapy patients from all other treatment groups had significantly elevated
      risk for exocrine hypogonadism. Patients from the other treatment groups, except
      those in the med-NHL group, also had significantly elevated risk for endocrine
      hypogonadism compared with the group treated with no/low gonadotoxic
      chemotherapy. Men aged above 50 years at survey were about five times more likely
      to have endocrine hypogonadism compared with those less than 40 years. Because of
      the adverse health effects following long-lasting endocrine hypogonadism, gonadal
      hormones should be assessed regularly in male lymphoma survivors, especially
      after treatment with alkylating agents and high-dose chemotherapy with autologous
      stem cell support and in male patients who are 50 years and older.

PMID- 19156144
TI  - An analysis of temporal and generational trends in the incidence of anal and
      other HPV-related cancers in Southeast England.
AB  - Patients diagnosed in 1960-2004 with cancer of the cervix, anus, vulva, vagina or
      penis were identified from the Thames Cancer Registry database, and age
      standardised period (temporal) incidence rates calculated by direct
      standardisation. Age-cohort modelling techniques were used to estimate age
      specific incidence rates in the earlier and later cohorts, enabling the
      calculation of age-standardised cohort (generational) rates. Incidence of anal
      cancer increased for both men and women over the period studied, mainly in those
      born from 1940 onwards. Similar generational patterns were seen for cancers of
      the vulva and vagina, but those for penile cancer were different. For cervix
      cancer, the steep downward trend in cohort rates due to screening levelled off in
      women born from 1940 onwards. Our findings are compatible with the hypothesis
      that changes in sexual practices were a major contributor to the increases of
      these cancers. Programmes of vaccination against HPV, aimed at reducing the
      burden of cervical cancer, may also help to reduce the incidence of cancer at
      other anogenital sites.

PMID- 19156145
TI  - Dysregulation of the transcription factors SOX4, CBFB and SMARCC1 correlates with
      outcome of colorectal cancer.
AB  - The aim of this study was to identify deregulated transcription factors (TFs) in
      colorectal cancer (CRC) and to evaluate their relation with the recurrence of
      stage II CRC and overall survival. Microarray-based transcript profiles of 20
      normal mucosas and 424 CRC samples were used to identify 51 TFs displaying
      differential transcript levels between normal mucosa and CRC. For a subset of
      these we provide in vitro evidence that deregulation of the Wnt signalling
      pathway can lead to the alterations observed in tissues. Furthermore, in two
      independent cohorts of microsatellite-stable stage II cancers we found that high
      SOX4 transcript levels correlated with recurrence (HR 2.7; 95% CI, 1.2-6.0;
      P=0.01). Analyses of approximately 1000 stage I-III adenocarcinomas, by
      immunohistochemistry, revealed that patients with tumours displaying high levels
      of CBFB and SMARCC1 proteins had a significantly better overall survival rate
      (P=0.0001 and P=0.0275, respectively) than patients with low levels. Multivariate
      analyses revealed that a high CBFB protein level was an independent predictor of
      survival. In conclusion, several of the identified TFs seem to be involved in the
      progression of CRC.

PMID- 19156146
TI  - Validation study of the prognostic value of cyclin-dependent kinase (CDK)-based
      risk in Caucasian breast cancer patients.
AB  - In a Japanese study, cyclin-dependent kinase (CDK) based risk determined by CDK 1
      and 2 activities was associated with risk of distance recurrence in early breast
      cancer patients. The aim of our study was to validate this risk categorization in
      European early breast cancer patients. We retrospectively analyzed frozen breast
      cancer specimens of 352 Dutch patients with histologically confirmed primary
      invasive early breast cancer. CDK-based risk was determined in tumour tissues by
      calculating a risk score (RS) according to kinases activity and protein mass
      concentration assay without the knowledge of outcome. Determination of CDK-based
      risk was feasible in 184 out of 352 (52%) tumours. Median follow-up of these
      patients was 15 years. In patients not receiving systemic treatment, the
      proportions of risk categories were 44% low, 16% intermediate, and 40% high CDK
      based risk. These groups remained significant after univariate and multivariate
      Cox-regression analysis. Factors associated with a shorter distant recurrence
      free period were positive lymph nodes, mastectomy with radiotherapy, and high CDK
      based risk. There was no significant correlation with overall survival (OS). CDK
      based risk is a prognostic marker of distance recurrence of patients with early
      breast cancer. More validation would be warranted to use of CDK-based risk into
      clinical practice.

PMID- 19156147
TI  - Frequent overexpression of HMGA1 and 2 in gastroenteropancreatic neuroendocrine
      tumours and its relationship to let-7 downregulation.
AB  - The molecular pathogenesis of gastroenteropancreatic (GEP) neuroendocrine tumours
      (NETs) remains to be elucidated. High-mobility group A (HMGA) proteins play
      important roles in the regulation of transcription, differentiation, and
      neoplastic transformation. In this study, the expression of HMGA1 and HMGA2 was
      studied in 55 GEP NETs. Overexpression of HMGA1 and 2 was frequently detected in
      GEP NETs compared with normal tissues. Nuclear immunostaining of HMGA1 and 2 was
      observed in GEP NETs (38 of 55, 69%; 40 of 55, 73%, respectively). High-mobility
      group A2 expression increased from well-differentiated NET (WNET) to well
      differentiated neuroendocrine carcinoma (WNEC) and poorly differentiated NEC
      (PNEC) (P<0.005) and showed the highest level in stage IV tumours (P<0.01). In
      WNECs, the expression of HMGA1 and 2 was significantly higher in metastatic
      tumours than those without metastasis (P<0.05). Gastroenteropancreatic NETs in
      foregut showed the highest level of HMGA1 and 2 expressions. MIB-1 labelling
      index (MIB-1 LI) correlated with HMGA1 and 2 overexpression (R=0.28, P<0.05;
      R=0.434, P<0.001; respectively) and progressively increased from WNETs to WNECs
      and PNECs (P<0.001). Let-7 expression was addressed in 6 normal organs, 30 tumour
      samples, and 24 tumour margin non-tumour tissues. Compared with normal tissues,
      let-7 downregulation was frequent in NETs (19 of 30, 63%). Higher expression of
      HMGA1 and 2 was frequently observed in tumours with let-7 significant reduction
      (53, 42%, respectively). The reverse correlation could be detected between HMGA1
      and let-7 (P<0.05). Our findings suggested that HMGA1 and 2 overexpression and
      let-7 downregulation might relate to pathogenesis of GEP NETs.

PMID- 19156148
TI  - Family history of haematopoietic malignancies and non-Hodgkin's lymphoma risk in
      the California Teachers Study.
AB  - Family history of haematopoietic malignancies appears to be a risk factor for non
      Hodgkin's lymphoma (NHL), but whether risk varies by family member's gender is
      unclear. Among 121 216 women participating in the prospective California Teachers
      Study, NHL risk varied by type of haematopoietic malignancy and gender of the
      relative.

PMID- 19156149
TI  - A randomised trial of intrapericardial bleomycin for malignant pericardial
      effusion with lung cancer (JCOG9811).
AB  - Safety and efficacy of intrapericardial (i.p.c.) instillation of bleomycin (BLM)
      following pericardial drainage in patients with malignant pericardial effusion
      (MPE) remain unclear. Patients with pathologically documented lung cancer, who
      had undergone pericardial drainage for MPE within 72 h of enrolment, were
      randomised to either arm A (observation alone after drainage) or arm B (i.p.c.
      BLM at 15 mg, followed by additional i.p.c. BLM 10 mg every 48 h). The drainage
      tube was removed when daily drainage was 20 ml or less. The primary end point was
      survival with MPE control (effusion failure-free survival, EFFS) at 2 months.
      Eighty patients were enrolled, and 79 were eligible. Effusion failure-free
      survival at 2 months was 29% in arm A and 46% in arm B (one-sided P=0.086 by
      Fisher's exact test). Arm B tended to favour EFFS, with a hazard ratio of 0.64
      (95% confidence interval: 0.40-1.03, one-sided P=0.030 by log-rank test). No
      significant differences in the acute toxicities or complications were observed.
      The median survival was 79 days and 119 days in arm A and arm B, respectively.
      This medium-sized trial failed to show statistical significance in the primary
      end point. Although ipc BLM appeared safe and effective in the management of MPE,
      the therapeutic advantage seems modest.

PMID- 19156150
TI  - Non-steroidal anti-inflammatory drugs and risk of gastric and oesophageal
      adenocarcinomas: results from a cohort study and a meta-analysis.
AB  - Use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) may reduce
      the risk of gastric or oesophageal adenocarcinomas. We examined the association
      between self-reported use of aspirin or non-aspirin NSAIDs in the earlier 12
      months and gastric non-cardia (N=182), gastric cardia (N=178), and oesophageal
      adenocarcinomas (N=228) in a prospective cohort (N=311 115) followed for 7 years.
      Hazard ratios (HRs) and 95% confidence intervals (CIs) come from Cox models
      adjusted for potential confounders. Use of any aspirin (HR, 95% CI: 0.64, 0.47
      0.86) or other NSAIDs (0.68, 0.51-0.92) was associated with a significantly lower
      risk of gastric non-cardia adenocarcinoma. Neither aspirin (0.86, 0.61-1.20) nor
      other NSAIDs (0.91, 0.67-1.22) had a significant association with gastric cardia
      cancer. We found no significant association between using aspirin (1.00, 0.73
      1.37) or other NSAIDs (0.90, 69-1.17) and oesophageal adenocarcinoma. We also
      performed a meta-analysis of the association between the use of NSAIDs and risk
      of gastric and oesophageal adenocarcinoma. In this analysis, aspirin use was
      inversely associated with both gastric and oesophageal adenocarcinomas, with
      summary odds ratios (95% CI) for non-cardia, cardia, and oesophageal
      adenocarcinomas of 0.64 (0.52-0.80), 0.82 (0.65-1.04), and 0.64 (0.52-0.79),
      respectively. The corresponding numbers for other NSAIDs were 0.68 (0.57-0.81),
      0.80 (0.67-0.95), and 0.65 (0.50-0.85), respectively.

PMID- 19156152
TI  - Effects of a neuregulin 1 variant on conversion to schizophrenia and
      schizophreniform disorder in people at high risk for psychosis.

PMID- 19156153
TI  - Bias in genetic association studies and impact factor.

PMID- 19156154
TI  - The Met allele of the BDNF Val66Met polymorphism is associated with increased
      BDNF serum concentrations.

PMID- 19156156
TI  - Energy expenditure in young adult urban informal settlement dwellers in South
      Africa.
AB  - Obesity prevalences are increasing in industrialized and developing countries. As
      a pilot for a comparative study of physical activity and weight change, we
      assessed energy expenditure (EE) in young black South African adults living in an
      urban informal settlement. Total EE (TEE) was assessed using doubly labeled
      water, activity EE (AEE) and activity patterns by accelerometry and body
      composition by isotope dilution. Twenty young women and eight men were enrolled.
      Over 50% of the women and no men were obese (mean BMI 31.0 and 21.6 kg/m(2),
      respectively). Women had significantly lower TEE and AEE after adjustment for
      body size, as well as lower levels of moderate and vigorous activity. Neither TEE
      nor AEE was associated with BMI or percent body fat, whereas percent time in
      vigorous activity was modestly negatively associated with adiposity. These data
      add to the small literature on EE and activity among populations undergoing
      epidemiologic transitions.

PMID- 19156155
TI  - Consumption of medium- and long-chain triacylglycerols decreases body fat and
      blood triglyceride in Chinese hypertriglyceridemic subjects.
AB  - OBJECTIVES: To investigate the effects of medium- and long-chain triacylglycerol
      (MLCT) on blood triglyceride (TG) in Chinese hypertriglyceridemic subjects.
      METHODS: A double-blind controlled clinical trial was carried out, in which 112
      subjects with hypertriglyceridemia were randomly divided into two dietary oil
      groups: (1) long-chain triacylglycerol (LCT) and (2) MLCT. All subjects were
      requested to ingest fixed energy and to continue their normal activity levels,
      and to consume LCT or MLCT oil at 25-30 g daily during the study period.
      Anthropometric measurements of body weight, body mass index (BMI), body fat, body
      fat percentage, waist and hip circumference (WC and HC), areas of subcutaneous
      and visceral fat by computed tomography scanning and blood biochemical markers
      were measured at the beginning and end of the study. RESULTS: There were 50 and
      51 subjects left in LCT and MLCT groups, respectively. There were no significant
      differences in daily intake of energy, protein, fat and carbohydrate, as well as
      the daily physical activity between the two groups during the study. After 8
      weeks, MLCT group showed a significant decrease in body weight, BMI, WC, HC,
      ratio of WC and HC, body fat, body fat percentage and subcutaneous fat when
      compared with the initial values. The decrease in body weight, BMI, WC, body fat
      and subcutaneous and visceral fat was significantly greater in MLCT group than
      that in the LCT group. Furthermore, the serum concentrations of TG in MLCT group
      were significantly lower than those in the LCT group. CONCLUSIONS: Consumption of
      MLCT may reduce body weight, body fat and blood TG in hypertriglyceridemic
      subjects under an appropriate dietary regime.

PMID- 19156157
TI  - Prevalence of adult-type hypolactasia as diagnosed with genetic and lactose
      hydrogen breath tests in Hungarians.
AB  - The prevalence of adult-type hypolactasia varies ethnically and geographically
      among populations. A C/T(-13910) single nucleotide polymorphism (SNP), upstream
      of the lactase gene, is known to be associated with lactase non-persistence. The
      aim of this study was to determine the prevalence of lactase-persistent and non
      persistent genotypes in the Hungarian population, the age at onset and the
      applicability of the lactose H2 breath test in comparison with genetic screening.
      The prevalence of the C/C(-13910) genotype among adults was 37%. Hypolactasia
      starts to appear at around 5 years of age. Over the age of 12 years, almost all
      of those with a C/C(-13910) genotype have lactase non-persistence. The C/C(
      13910) genotype was closely associated with a positive lactose H2 breath test in
      symptomatic children, whereas the lactase-persistent genotypes correlated better
      with a negative H2 test in a control group. In conclusion, supplementary non
      invasive breath and genotyping tests furnish a perfect clinical diagnosis.

PMID- 19156158
TI  - Reduced mania and depression in juvenile bipolar disorder associated with long
      chain omega-3 polyunsaturated fatty acid supplementation.
AB  - Long-chain omega-3 polyunsaturated fatty acid (LCn-3PUFA) supplementation may
      improve symptoms of depression in children and bipolar disorder (BD) in adults.
      No studies have examined the effectiveness of LCn-3PUFA supplementation in the
      treatment of mania and depression in juvenile BD (JBD) when given as an adjunct
      to standard pharmacological treatment. Eighteen children and adolescents with JBD
      received supplements containing 360 mg per day eicosapentaenoic acid (EPA) and
      1560 mg per day docosahexaenoic acid (DHA) for 6 weeks in an open-label study.
      Intake and fasting red blood cell (RBC) LCn-3PUFA, mania, depression and global
      function were assessed before and after supplementation. RBC EPA and DHA were
      significantly higher following supplementation. Clinician ratings of mania and
      depression were significantly lower and global functioning significantly higher
      after supplementation. Parent ratings of internalizing and externalizing
      behaviours were also significantly lower following supplementation. A larger
      randomized controlled trial appears warranted in this participant population.

PMID- 19156159
TI  - Long-term effect of calcium-vitamin D(3) fortified milk on blood pressure and
      serum lipid concentrations in healthy older men.
AB  - BACKGROUND/OBJECTIVES: Some epidemiological and clinical studies have shown that
      increased dairy consumption or calcium and/or vitamin D supplementation can have
      a beneficial effect on blood pressure, and lipid and lipoprotein concentrations.
      The aim of this study was to assess the long-term effects of calcium-vitamin D(3)
      fortified milk on blood pressure and lipid-lipoprotein concentrations in
      community-dwelling older men. SUBJECTS/METHODS: This is a substudy of a 2-year
      randomized controlled trial in which 167 men aged >50 years were assigned to
      receive either 400 ml per day of reduced fat (approximately 1%) milk fortified
      with approximately 1000 mg of calcium and 800 IU of vitamin D(3) or to a control
      group receiving no additional fortified milk. Weight, blood pressure, lipid and
      lipoprotein concentrations were measured every 6 months. Participants on lipid
      lowering (n=32) or antihypertensive medication (n=39) were included, but those
      who commenced, increased or decreased their medication throughout the
      intervention were excluded (n=27). RESULTS: In the 140 men included in this study
      (milk, n=73; control, n=67), there were no significant effects of the calcium
      vitamin D(3) fortified milk on weight, systolic or diastolic blood pressure,
      total cholesterol, high-density lipoprotein or low-density lipoprotein
      cholesterol or triglyceride concentrations at any time throughout the
      intervention. Similar results were observed after excluding men taking
      antihypertensive or lipid-lowering medication or limiting the analysis to those
      with baseline calcium intakes <1000 mg per day and/or with hypovitaminosis D
      (25(OH)D <75 nmol/l). CONCLUSIONS: Supplementation with reduced-fat calcium
      vitamin D(3) fortified milk did not have a beneficial (nor detrimental) effect on
      blood pressure, lipid or lipoprotein concentrations in healthy community-dwelling
      older men.

PMID- 19156160
TI  - The impact of microRNAs and alternative splicing in pharmacogenomics.

PMID- 19156161
TI  - Fast isotopic exchange between mitochondria and cytosol in brain revealed by
      relayed 13C magnetization transfer spectroscopy.
AB  - In vivo 13C magnetic resonance spectroscopy has been applied to studying brain
      metabolic processes by measuring 13C label incorporation into cytosolic pools
      such as glutamate and aspartate. However, the rate of exchange between
      mitochondrial alpha-ketoglutarate/oxaloacetate and cytosolic glutamate/aspartate
      (Vx) extracted from metabolic modeling has been controversial. Because brain
      fumarase is exclusively located in the mitochondria, and mitochondrial fumarate
      is connected to cytosolic aspartate through a chain of fast exchange reactions,
      it is possible to directly measure Vx from the four-carbon side of the
      tricarboxylic acid cycle by magnetization transfer. In isoflurane-anesthetized
      adult rat brain, a relayed 13C magnetization transfer effect on cytosolic
      aspartate C2 at 53.2 ppm was detected after extensive signal averaging with
      fumarate C2 at 136.1 ppm irradiated using selective radiofrequency pulses.
      Quantitative analysis using Bloch-McConnell equations and a four-site exchange
      model found that Vx approximately 13-19 micromol per g per min (>>VTCA, the
      tricarboxylic acid cycle rate) when the longitudinal relaxation time of malate C2
      was assumed to be within +/-33% of that of aspartate C2. If Vx approximately
      VTCA, the isotopic exchange between mitochondria and cytosol would be too slow on
      the time scale of 13C longitudinal relaxation to cause a detectable magnetization
      transfer effect.

PMID- 19156162
TI  - Time-course of cerebral perfusion and tissue oxygenation in the first 6 h after
      experimental subarachnoid hemorrhage in rats.
AB  - Present knowledge about hemodynamic and metabolic changes after subarachnoid
      hemorrhage (SAH) originates from neuromonitoring usually starting with aneurysm
      surgery and animal studies that have been focusing on the first 1 to 3 h after
      SAH. Most patients, however, are referred to treatment several hours after the
      insult. We examined the course of hemodynamic parameters, cerebral blood flow,
      and tissue oxygenation (ptiO2) in the first 6 h after experimental SAH. Sixteen
      Sprague-Dawley rats were subjected to SAH using the endovascular filament model
      or served as controls (n=8). Bilateral local cortical blood flow, intracranial
      pressure, cerebral perfusion pressure, and ptiO2 were followed for 6 h after SAH.
      After induction of SAH, local cortical blood flow rapidly declined to 22% of
      baseline and returned to 80% after 6 h. The decline of local cortical blood flow
      markedly exceeded the decline of cerebral perfusion pressure. ptiO2 declined to
      57%, recovered after 2 h, and reached > or =140% of baseline after 6 h. Acute
      vasoconstriction after SAH is indicated by the marked discrepancy of cerebral
      perfusion pressure and local cortical blood flow. The excess tissue oxygenation
      several hours after SAH suggests disturbed oxygen utilization and cerebral
      metabolic depression. Aside from the sudden increase of intracranial pressure at
      the time of hemorrhage and delayed cerebral vasospasm, the occurrence of acute
      vasoconstriction and disturbed oxygen utilization may be additional factors
      contributing to secondary brain damage after SAH.

PMID- 19156163
TI  - Shared susceptibility variations in autoimmune diseases: a brief perspective on
      common issues.

PMID- 19156164
TI  - Genetic markers in the playground of multivariate analysis.
AB  - Multivariate analyses such as principal component analysis were among the first
      statistical methods employed to extract information from genetic markers. From
      their early applications to current innovations, these approaches have proven to
      be efficient for the analysis of the genetic variability in various contexts such
      as human genetics, conservation and adaptation studies. However, because
      multivariate analysis is a wide and diversified area of statistics, choosing a
      method appropriate to both the data and to the question being asked can be
      difficult. Moreover, some particularities of genetic markers need to be taken
      into account when using multivariate methods. As a consequence, multivariate
      analyses are often used as black boxes, which results in frequent mistakes in the
      literature. In this review, we provide a critical analysis of the application of
      multivariate methods to genetic markers, using a general framework that unifies
      all these methods for the sake of clarity. First, we focus on some common
      mistakes in these applications and ways to avoid these pitfalls. We then detail
      the most critical particularities of allele frequencies that demand adaptations
      of multivariate methods, and we propose solutions to the subsequent problems.
      Finally, we tackle several questions of interest in which multivariate analysis
      has a great role to play, such as the study of the typological coherence of
      different genetic markers, or the investigation of spatial genetic patterns.

PMID- 19156165
TI  - European phylogeography of the common frog (Rana temporaria): routes of
      postglacial colonization into the British Isles, and evidence for an Irish
      glacial refugium.
AB  - We use phylogenetic techniques to investigate the postglacial re-population of
      Europe by the common frog and, in particular, the colonization of Ireland. Three
      main hypotheses have been proposed for the re-establishment of the Irish fauna
      after the last ice age: arrival across a late-glacial land bridge from Britain;
      expansion from a glacial refuge in the south of Ireland and, for some species, re
      introduction by humans from Iberia. We examined the phylogeographic structure of
      52 populations of the common frog (Rana temporaria) throughout Europe using 476
      bp mitochondrial cytochrome b gene sequences. Our data replicate earlier studies
      in showing substantial sequence divergence (3%) between Eastern and Western
      European common frog haplotypes. However, we uncover a new evidence that these
      haplotypes co-exist in Spain, Switzerland and France, and infer an expansion of
      the eastern clade along the Mediterranean coastal corridor. All the British
      samples fall within the Western European clade, but the Irish data imply a
      different history. Genetically distinct haplotypes occur in populations from the
      south-west of Ireland. This local genetic differentiation may be a consequence of
      a local glacial refuge, possibly combined with natural colonization or
      introduction from Western Europe.

PMID- 19156166
TI  - IFIH1-GCA-KCNH7 locus is not associated with genetic susceptibility to multiple
      sclerosis in French patients.
AB  - A recent investigation reported, for the first time, an association between
      variants in the IFIH1-GCA-KCNH7 locus and multiple sclerosis (MS). We sought to
      replicate this genetic association in MS with a new independent MS cohort
      composed of French Caucasian MS trio families. The two most significant IFIH1
      single nucleotide polymorphisms, rs1990760 and rs2068330, reported as involved in
      MS susceptibility, were genotyped in 591 French Caucasian MS trio families, and
      analyzed using the transmission/disequilibrium test. No association with MS was
      found (rs1990760, P=0.45 and rs2068330, P=0.27). Similarly, no significant
      association was detected after stratification for HLA-DRB1*1501 carriers. Reasons
      that may explain this discrepancy between the original report and our study are
      discussed.

PMID- 19156167
TI  - Incidence of non-age-dependent chromosomal abnormalities: a population-based
      study on 88965 amniocenteses.
AB  - Current knowledge about the incidence of chromosomal abnormalities in the general
      population comes from studies in newborns carried out in the 70s, before the era
      of widespread prenatal diagnosis. In the following years, data on frequency of
      chromosomal abnormalities in the second trimester of pregnancy have been used in
      conjunction with the data on the natural history of chromosomally abnormal
      fetuses to infer maternal age-specific rates of cytogenetic abnormalities in live
      born infants. Starting from the data gathered in 1995-1996 from all Italian
      cytogenetic laboratories (with 92% compliance to the study), we have compared the
      frequency of chromosomal abnormalities at amniocentesis in cases with maternal
      age of >or=35 years (51,758 individuals) and cases with maternal age of <35 years
      (37,207 cases). The comparison confirmed the age-dependency of aneuploidies,
      whereas none of the structural abnormalities showed age-related differences.
      Furthermore, among the mosaic aneuploidies, trisomy 21 and 45,X/46,XX were found
      with a significantly higher incidence in older women. Chromosomal abnormalities
      that showed no significant difference between the two groups were summed for the
      overall national cohort, providing a general estimate of the incidence in the
      second trimester of pregnancy. The data provide critical background information
      for prenatal genetic counseling and for the planning of health care policy.

PMID- 19156168
TI  - Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene
      analysis.
AB  - The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Phase 1
      Schizophrenia trial compared the effectiveness of one typical and four atypical
      antipsychotic medications. Although trials such as CATIE present important
      opportunities for pharmacogenetics research, the very richness of the clinical
      data presents challenges for statistical interpretation, and in particular the
      risk that data mining will lead to false-positive discoveries. For this reason,
      it is both misleading and unhelpful to perpetuate the current practice of
      reporting association results for these trials one gene at a time, ignoring the
      fact that multiple gene-by-phenotype tests are being carried out on the same data
      set. On the other hand, suggestive associations in such trials may lead to new
      hypotheses that can be tested through both replication efforts and biological
      experimentation. The appropriate handling of these forms of data therefore
      requires dissemination of association statistics without undue emphasis on select
      findings. Here we attempt to illustrate this approach by presenting association
      statistics for 2769 polymorphisms in 118 candidate genes evaluated for 21
      pharmacogenetic phenotypes. On current evidence it is impossible to know which of
      these associations may be real, although in total they form a valuable resource
      that is immediately available to the scientific community.

PMID- 19156169
TI  - Type A microsatellite instability in pediatric gliomas as an indicator of Turcot
      syndrome.
AB  - Microsatellite instability (MSI) is present in hereditary conditions due to
      mismatch repair (MMR) gene mutations. Following MSI analysis, tumor samples are
      classified into MSS (stable), MSI-L (low instability), and MSI-H (high
      instability) based on the fraction of unstable loci. Another MSI-based
      classification takes into account the size difference between mutant alleles in
      tumor DNA compared to wild-type alleles; two types of MSI, A and B, are
      recognized using this approach, type A being characterized by smaller, more
      subtle allelic shifts compared to type B. Biallelic mutations of MMR genes are
      associated with pediatric cancers, including glial tumors, in Turcot syndrome
      type 1 (TS1). However, most TS1-associated gliomas so far analyzed did not
      display MSI. We investigated the frequency of MSI in a series of 34 pediatric
      gliomas of different grade using a panel of five mononucleotide quasimonomorphic
      markers. Subtle qualitative changes were observed for the majority of markers in
      two glioblastomas (5.9% of the total series and 33.3% of glioblastomas). In both
      cases, family histories were compatible with TS1, and mutations of the PMS2 and
      MLH1 genes were identified. In one family, the MSI patterns were compared between
      the glioblastoma and a colon cancer from an affected relative, showing a clear
      qualitative difference, with the former displaying type A and the latter type B
      instability, respectively. These results were confirmed using additional
      microsatellite markers, indicating that knowledge of the association between TS1
      related glial tumors and subtle type A MSI is important for full ascertainment of
      TS1 patients and appropriate counselling.

PMID- 19156170
TI  - Moors and Saracens in Europe: estimating the medieval North African male legacy
      in southern Europe.
AB  - To investigate the male genetic legacy of the Arab rule in southern Europe during
      medieval times, we focused on specific Northwest African haplogroups and
      identified evolutionary close STR-defined haplotypes in Iberia, Sicily and the
      Italian peninsula. Our results point to a higher recent Northwest African
      contribution in Iberia and Sicily in agreement with historical data. southern
      Italian regions known to have experienced long-term Arab presence also show an
      enrichment of Northwest African types. The forensic and genomic implications of
      these findings are discussed.

PMID- 19156171
TI  - An 8.9 Mb 19p13 duplication associated with precocious puberty and a sporadic 3.9
      Mb 2q23.3q24.1 deletion containing NR4A2 in mentally retarded members of a family
      with an intrachromosomal 19p-into-19q between-arm insertion.
AB  - In a 2 and a half-year-old girl with onset of puberty before the age of 5 months,
      short stature, hand anomalies and severe mental retardation, an 8.9 Mb
      interstitial 19p13 duplication containing 215 predicted genes was detected. It
      was initially assumed that the duplication involved the kisspeptin receptor gene,
      GPR54, known to stimulate induction of puberty, but more refined duplication
      mapping excluded this possibility. In an attempt to further understand the
      genotype-phenotype correlation, global gene expression was measured in skin
      fibroblasts. The overall expression pattern was quite similar to controls, and
      only about 25% of the duplicated genes had an expression level that was increased
      by more than 1.3-fold, with no obvious changes that could explain the precocious
      puberty. The proband's mother carried a balanced between-arm insertion of the
      duplicated segment that resembled a pericentric inversion. The same insertion was
      found in several other family members, including one who had lost a daughter with
      severe mental retardation and menarche at the age of 10 years. Another close
      relative was severely mentally retarded, but neither dysmorphic nor
      microcephalic. His phenotype was initially ascribed to a presumed cryptic
      chromosome 19 imbalance caused by the 19p-into19q insertion, but subsequent array
      CGH detected a 3.9-Mb deletion of 2q23.3q24.1. This novel microdeletion involves
      seven genes, of which FMNL2, a suggested regulator of Rho-GTPases, and NR4A2, an
      essential gene for differentiation of dopaminergic neurons, may be critical genes
      for the proposed 2q23q24 microdeletion syndrome.

PMID- 19156172
TI  - Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and
      genotype-phenotype correlations.
AB  - Cardio-facio-cutaneous syndrome (CFCS) is a rare disease characterized by mental
      retardation, facial dysmorphisms, ectodermal abnormalities, heart defects and
      developmental delay. CFCS is genetically heterogeneous and mutations in the KRAS,
      BRAF, MAP2K1 (MEK1) and MAP2K2 (MEK2) genes, encoding for components of the RAS
      mitogen activated protein kinase (MAPK) signaling pathway, have been identified
      in up to 90% of cases. Here we screened a cohort of 33 individuals with CFCS for
      MEK1 and MEK2 gene mutations to further explore their molecular spectrum in this
      disorder, and to analyze genotype-phenotype correlations. Three MEK1 and two MEK2
      mutations were detected in six patients. Two missense MEK1 (L42F and Y130H)
      changes and one in-frame MEK2 (K63_E66del) deletion had not been reported
      earlier. All mutations were localized within exon 2 or 3. Together with the
      available records, the present data document that MEK1 mutations are relatively
      more frequent than those in MEK2, with exons 2 and 3 being mutational hot spots
      in both genes. Mutational analysis of the affected MEK1 and MEK2 exons did not
      reveal occurrence of mutations among 75 patients with Noonan syndrome, confirming
      the low prevalence of MEK gene defects in this disorder. Clinical review of known
      individuals with MEK1/MEK2 mutations suggests that these patients show dysmorphic
      features, ectodermal abnormalities and cognitive deficit similar to what was
      observed in BRAF-mutated patients and in the general CFCS population. Conversely,
      congenital heart defects, particularly mitral valve and septal defects, and
      ocular anomalies seem to be less frequent among MEK1/MEK2 mutation-positive
      patients.

PMID- 19156173
TI  - Suggestive linkage of ADHD to chromosome 18q22 in a young genetically isolated
      Dutch population.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable,
      neuropsychiatric disorder among children. Linkage studies in isolated populations
      have proved powerful to detect variants for complex diseases, such as ADHD. We
      performed a genome-wide linkage scan for ADHD in nine patients from a genetically
      isolated population in the Netherlands, who were linked to each other within 10
      generations through multiple lines of descent. The genome-wide scan was performed
      with a set of 400 microsatellite markers with an average spacing of +/-10-12 cM.
      We performed multipoint parametric linkage analyses using both recessive and
      dominant models. Our genome scan pointed to several chromosomal regions that may
      harbour ADHD susceptibility genes. None exceeded the empirical genome-wide
      significance threshold, but the Log of odds (LOD) scores were >1.5 for regions
      6p22 (Heterogenetic log of odds (HLOD)=1.67) and 18q21-22 (HLOD=2.13) under a
      recessive model. We followed up these two regions in a larger sample of ADHD
      patients (n=21, 9 initial and 12 extra patients). The LOD scores did not increase
      after increasing the sample size (6p22 (HLOD=1.51), 18q21-22 (HLOD=1.83)).
      However, the LOD score on 6p22 increased to 2 when a separate analysis was
      performed for the inattentive type ADHD children. The linkage region on
      chromosome 18q overlaps with the findings of association of rs2311120 (P=10(-5))
      and rs4149601 (P=10(-4)) in the genome-wide association analysis for ADHD
      performed by the Genetic Association Information Network consortium. Furthermore,
      there was an excess of regions harbouring serotonin receptors (HTR1B, HTR1E,
      HTR4, HTR1D, and HTR6) that showed a LOD score >1 in our genome-wide scan.

PMID- 19156174
TI  - MTHFR 677 C>T and 1298 A>C polymorphisms and the age of onset of colorectal
      cancer in hereditary nonpolyposis colorectal cancer.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome is
      characterized by inactivating germline mutations in DNA mismatch repair genes
      resulting in an increased risk of developing an epithelial malignancy. There is
      considerable variability in disease expression observed in this syndrome, which
      is thought to be due to a combination of genetic and environmental factors.
      Alterations in the kinetics of methylene tetrahydrofolate reductase (MTHFR) due
      to the presence of polymorphisms in the MTHFR gene have been associated with an
      increased risk of colorectal cancer (CRC). Two common single nucleotide
      polymorphisms (SNPs) located within the MTHFR gene, 677 C>T and 1298 A>C, that
      alter the function of the encoded protein have been the focus of many studies on
      CRC risk outside the context of an inherited predisposition to disease. In this
      report, a total of 417 HNPCC participants were genotyped for the 677 C>T and 1298
      A>C SNPs to determine whether there exists an association with the age of disease
      onset of CRC. Genotyping of both SNPs was performed by TaqMan(R) assay
      technology. Associations in disease risk were further investigated using Kaplan
      Meier survival analysis and Cox hazard regression. The average ages of disease
      diagnosis were found to be different between individuals harbouring either one of
      the MTHFR polymorphisms. Both Kaplan-Meier and Cox hazard regression analyses
      revealed a more complex relationship between the two polymorphisms and the age of
      CRC onset. The Kaplan-Meier survival analysis revealed that compound
      heterozygotes for the two SNPs developed CRC 10 years later compared with those
      carrying only wild-type alleles.

PMID- 19156176
TI  - [Original articles comments].

PMID- 19156175
TI  - An evaluation of the genetic-matched pair study design using genome-wide SNP data
      from the European population.
AB  - Genetic matching potentially provides a means to alleviate the effects of
      incomplete Mendelian randomization in population-based gene-disease association
      studies. We therefore evaluated the genetic-matched pair study design on the
      basis of genome-wide SNP data (309,790 markers; Affymetrix GeneChip Human Mapping
      500K Array) from 2457 individuals, sampled at 23 different recruitment sites
      across Europe. Using pair-wise identity-by-state (IBS) as a matching criterion,
      we tried to derive a subset of markers that would allow identification of the
      best overall matching (BOM) partner for a given individual, based on the IBS
      status for the subset alone. However, our results suggest that, by following this
      approach, the prediction accuracy is only notably improved by the first 20
      markers selected, and increases proportionally to the marker number thereafter.
      Furthermore, in a considerable proportion of cases (76.0%), the BOM of a given
      individual, based on the complete marker set, came from a different recruitment
      site than the individual itself. A second marker set, specifically selected for
      ancestry sensitivity using singular value decomposition, performed even more
      poorly and was no more capable of predicting the BOM than randomly chosen
      subsets. This leads us to conclude that, at least in Europe, the utility of the
      genetic-matched pair study design depends critically on the availability of
      comprehensive genotype information for both cases and controls.

PMID- 19156177
TI  - [Clinical, biochemical and hepatic histological findings in overweight and obese
      Peruvian adults: first national prospective study].
AB  - We conducted a prospective, descriptive study in the Clinica Anglo Americana, a
      private institution taking care of patients from a medium-high socioeconomic
      level in Lima. The goal of the study was to determine the frequency of histologic
      findings in liver biopsies performed by laparoscopy or percutaneously in patients
      with overweight (body mass index > 25 kg/m2) or obesity (body mass index > 30
      kg/m2), and to evaluate the correlation with antropometric variables such as BMI,
      waist circumference, history of diabetes or hyperlypidemia, and biochemical
      variables like glycemia, lipid profile, aminotransferases and AST/ALT ratio.
      Between the years 2001 and 2006 50 patients were biopsied, 29 with overweight and
      21 with obesity. Eighteen had simple steatosis and 22 had Non-alcoholic
      steatohepatitis (NASH) (44%), so 40 patients (80%) had some form of fatty liver.
      Five patients (10%) had cirrhosis confirmed by biopsy, and in all of them the
      finding of cirrhosis was completely incidental. Sixty four percent of patients
      with NASH were obese, like the 5 cirrhotics in our series. Herein we illustrate
      that in a relatively small sample of patients with obesity and overweight like
      ours, we found all the forms of the liver steatosis spectrum, from simple
      steatosis to cirrhosis, with a high frequency of NASH.

PMID- 19156178
TI  - [Endoscopic Submucosal dissection and mucosectomy for the treatment of the
      epithelial neoplasia and early gastric cancer].
AB  - INTRODUCTION: In Japan, endoscopic mucosal resection and endoscopic submucosal
      dissection of early gastric cancer are accepted as a treatment options for cases
      of early gastric cancer where the probability of lymph node metastasis is nil or
      low. OBJECTIVES: To establish the effectiveness of mucosectomy for the treatment
      of early gastric cancer and evaluate the extended indications for dysplasia
      lesions, also, we want to determine if the mucosectomy is relevant for lesions
      negative for neoplasia at the National Institute for Neoplastic Diseases (INEN),
      Lima, Peru. We call for estimating the utility and factibility of the endoscopic
      submucosa dissection with the needle knife. MATERIALS AND METHODS: The study is
      an observational, prospective, analytical and cross longitudinal. The study was
      performed in 96 patients with Type 0 Neoplastic lesions at INEN from 1996 to
      2008. The revised Vienna classification of gastrointestinal epithelial neoplasia
      was utilized. The indication for endoscopic mucosal resection as a radical
      treatment of early gastric cancer is according to the treatment guidelines for
      gastric cancer in Japan. The lesions were resected with a simple endoscopic
      snare, with the Olympus cap for some depressed lesions and the needle knife
      during the submucosal dissection. Lifting of the lesion with submucosal injection
      was done with saline solution with epinephrine or saline with distillate water.
      The statistical analysis included the SPPS-12 programme. RESULTS: 96 patients
      were treated by mucosectomy and endoscopic submucosal dissection from 1996 to
      2008. The sample represents patients with a mean age over 50 years old and
      predominance of female. 55 patients belongs to category 1 of revised Vienna
      Classification, 9 patients are in the category 3, 31 patients are suitable in
      category 4 (20 with high grade adenoma/dysplasia and 11 with intramucosal
      carcinoma) and just 1 patient for the category 5. We resected 305 Type 0 lesions,
      85 mucosal neoplasia, low grade (43) and high grade (31 adenoma/dysplasia in 20
      patients and 11 intramucosal carcinoma in 11 patients), and 219 lesions negatives
      for neoplasia. Approximately 200 lesions were resected by mucosectomy. The
      endoscopic submucosal dissection was done in 03 patients with additional
      mucosectomy. In general, the complications were bleeding resolved during the same
      procedure; there were no perforations in the current series. The local recurrence
      of 2 adenomas (high and low dysplasia), were resolved with Plasma Argon. We have
      no evidence of neither local nor distant recurrence in patients with intramucosal
      carcinoma in 5-10 years follow up. The patient treated by mucosectomy and
      submucosal invasion was operated and his actual survival is 6 years and 7 months.
      CONCLUSIONS: Mucosectomy is effective for precise variety of early gastric cancer
      with a median follow up period of 5-10 years in ours first patients, preserve the
      organ and maintain a high quality of life. Mucosectomy is appropriated for
      mucosal low and high grade adenoma/dysplasia, the local recurrence can be treated
      by Plasma Argon. The procedure can extend the indications eventually for lesions
      that are non-neoplasia. The endoscopic submucosal dissection must be done only in
      trained centres.

PMID- 19156179
TI  - [Pseudopapillary solid tumor of pancreas in the INEN].
AB  - OBJECTIVE: To determine the frequency of pancreas solid-pseudopapillary tumor
      (SPT) and to describe its clinical, pathological and immunohistochemical features
      in the National Institute of Neoplasic Diseases (INEN). MATERIAL AND METHODS:
      Cross-sectional, Retrospective and Descriptive study of 28 SPT cases with clinic
      history, slides and paraffin blocks for the revision and inmunohistochemical
      examination. Tissue Microarray technique was used and avidin-biotin method in the
      necessary cases. The statistical processing was made with SPSS 13.0 program.
      RESULTS: The SPT accounts for 3.7% of pancreatic tumors in the INEN. 24 patients
      were female (85.7%) and 4 male (14.3%) with average age 25.61years old.
      Clinically 50% displayed abdominal pain. There was no Ca 19-9 abnormal value. Two
      metastasis cases were found, one of them died. The average tumor size was 10.0
      cm. and the most frequent location was the head of the pancreas. Histologically
      is a monoforme pattern neoplasia, that displays pseudopapillae, rosettes,
      cholesterol crystals, sclerosis and calcification. The vascular infiltration,
      perineural, mitosis and nuclear atipia appeared in malignant cases.
      Immunohistochemically were vimentin and progesterone positive in the most cases.
      CONCLUSIONS: SPT is uncommon tumor with clinical, pathological and
      inmunohistochemical defined features. It is less aggressive than other pancreatic
      tumors, nevertheless its uncertain behavior demands follow up.

PMID- 19156180
TI  - [Vascular lesions of the upper gastrointestinal tract in the national hospital
      Daniel A. Carrion (2007-2008)].
AB  - To display the experience of vascular lesions in the upper digestive tract in
      2007-2008 at Daniel Alcides Carrion Hospital. METHODOLOGY: Transverse study. All
      endoscopies performed in the indicated period were reviewed. Vascular lesions
      found were record. The OMED classification for vascular lesions was used in this
      research. RESULTS: 1.979 examinations were reviewed. 26 vascular injuries were
      found (prevalence = 13.13/1000 endoscopies). The most frequent location was in
      stomach (65.4%). The most common type of injury was vascular angiectasia(57.7%).
      CONCLUSION: Vascular lesions in the upper digestive tract were rare; these
      lesions were more common in the stomach. Vascular angiectasias were the most
      frequently reported.

PMID- 19156181
TI  - [Use of propofol administered by nurse for the sedation during coloscopies in a
      national hospital in Lima - Peru].
AB  - INTRODUCTION: Propofol is becoming a widely used drug in patient sedation for
      patients that undergo endoscopic procedures. There are no reports on the use of
      propofol in public hospitals in Peru. OBJECTIVE: To describe our experience in
      propofol use in colonoscopies performed at Hospital Nacional Cayetano Heredia
      administered by a dedicated nurse with clinical and pulse oximetry monitorization
      in procedures performed by gastroenterologists and in-training residents of
      gastroenterology. MATERIAL AND METHODS: An observational and prospective study
      was performed at the Gastroenterology unit of Hospital Nacional Cayetano Heredia
      from Lima, Peru from January 2007 to April 2008. Patients were chosen on arrival
      to get an appointment for colonoscopy provided they did not have any exclusion
      criteria. Midazolam and meperidine IV premedication was administered prior to
      attack dose administration of propofol followed by boluses administered according
      to the nurse and physician assessment of the patient's pulse oximetry,
      ventilation, sedation and tolerance to the procedure. RESULTS: 163 colonoscopies
      were performed. Medium dose of propofol was 89.51mg (range 30mg - 220mg). 5,5% of
      patients had oxygen saturation less than 90% during the procedure but none
      required mask ventilation. There were no other complications. Procedure was
      performed by a gastroenterologist and by an in-training resident of
      gastroenterology. The same and only nurse was in charge of sedation in every
      procedure. Sedation degree achieved by patients in SAS scale (sedation agitation
      scale) was 3 (Sedated) in 66,26% and 4 (Calm and cooperative) in 29,45%. No
      patient had scales 1 (unarousable), 6 (very agitated) or 7 (dangerous agitation).
      CONCLUSION: Propofol sedation can be safely administered by a trained nurse with
      only pulse oximetry and clinical monitorization in colonoscopies performed by
      gastroenterologist as well as in-training residents of gastroenterology, being a
      very comfortable procedure both for patients and endoscopists.

PMID- 19156182
TI  - [Breaking paradigms in the acute severe pancreatitis: a new vision in the
      treatment of the disease].
AB  - The treatment of the severe acute pancreatitis has changed too fast in the last
      years and the new tendencies and continuous updates are forcing us to constantly
      vary the disease management protocols taking into account that what is true for
      today may prove to be a mistake tomorrow.In the Severe Acute Pancreatitis Unit of
      Eduardo Rebagliati Martins Hospital we believe there are four paradigms that can
      change the way we treat the disease.In the Unit we believe that a prophylactic
      antibiotic therapy is not effective in diminishing the incidence of infected
      necrosis nor in decreasing the death rate among patients with acute pancreatitis
      with necrosis, since the works published in the last two years make evident the
      clear tendency to the inefficiency of this therapy.In the protocol of the Unit
      there is no indication for surgical intervention of sterile necrosis since the
      surgical treatment could become the factor increasing the severity of the case
      that would cause higher death rates among patients with sterile pancreatic
      necrosis.The only and true absolute indication for surgery is a positive fine
      needle punction which discards "sepsis in the absence of an extrapancreatic
      source of infection" as surgical indication and allows the presence of gas in the
      tomography to be a relative indication for surgical intervention. In the Unit we
      consider that a pancreatic necrosectomy can be performed in one surgery as long
      as this can be delayed as much as possible.

PMID- 19156183
TI  - [Giant gastric ulcer by cytomegalovirus in infection VIH/SIDA].
AB  - Cytomegalovirus infection is an important cause of morbidity in immunosupressed
      patients with Human Immunodeficiency Virus (HIV). In this paper we present a 43
      years old man with renal failure under hemodialysis, several blood transfusions
      because of anemia and three months of disease characterized by epigastric pain,
      specially at nights, ameliorated with antacid drugs. Other symptoms were early
      satisfy, vomits and weigh loss (18Kg). At clinical exam, the patient was pallid,
      presented adenopathies at cervical and inguinal regions and had a pain at
      epigastric region in profound touch palpation. The most important exams were HB:
      10mg/dl, CMV: 83.5, leukocytes 7000, lymphocytes: 1715, erythrocyte sedimentation
      rate 49mm/h, the venon test (-), and Giardia lamblia trophozoites in stools. The
      studies demonstrated the patient was seropositive for HIV and the tests for IgG
      CMV and IgG Herpes virus resulted seropositives too. At endoscopy the esophagus
      mucosa was covered by a white plaque which suggests candida infection. In the
      stomach, over the body gastric, we found a big and deep ulcerated lesion (45 x
      41mm), with defined rims and white fund. Biopsy from the edges of the gastric
      ulcer had the characteristic CMV intranuclear and intracytoplasmic inclusions; we
      confirmed the diagnosis by immunohystochemistry. The patient receives ganciclovir
      an then HAART and is getting well.

PMID- 19156184
TI  - [Neuroendocrine bases in the surgical treatment of the morbid obesity: two cases
      operated with the technique of Santoro, in the HERM].
AB  - OBJECTIVE: To report on a new surgical technique to treat morbid obesity ideated
      by Sergio Santoro , based in neuroendocrine physiological concepts. METHOD: The
      operation included sleeve gastrectomy, omentectomy and enterectomy, maintaining
      the initial 50-100 cm. of jejunum and final 250-200 cm. of ileum, with termino
      terminate anastomosis . To report two cases operated at the Rebagliati Hospital.
      RESULTS: Three months of the follow up both patients have early saciety,
      asintomatic, low odor of the feces ,weigth reduction was 17-20 Kg. with
      improvement of the surgical comorbidities especially diabetes and knee pain .
      CONCLUSIONS: This procedures creates a proportionally reduced gastrointestinal
      tract, leaving its basic functions unharmed. After Santoro II operation an
      adaptation of the gastric chamber size to hypercaloric diet and it removes the
      sources of ghrelin and aims at moderate restriction with early saciety by
      distention , omentectomy removes the sources of plasminogen activator inhibitor 
      1 (PAI-1) and resistin production, enterectomy leads more nutrients to the distal
      bowel and raising the levels of glucagon-like peptide -1 (GLP-1) , Peptide YY
      (PYY) and oxintomodulina (OXM) with desirable metabolic consequences. It does no
      use prosthesis and does not cause exclusion of gastrointestinal segments,
      suboclusion, malabsorption , blind endoscopic areas and the patients do not need
      nutritional support or to take vitamins.

PMID- 19156185
TI  - [Duplicate publication: a Peruvian case].

PMID- 19156188
TI  - The Missing Censoring Indicator Model and the Smoothed Bootstrap.
AB  - For right censored data with missing censoring indicators, sub-density function
      kernel estimators play a significant role for estimating a survival function.
      Data-driven bandwidths for computing these kernel estimators are proposed. The
      bandwidths are obtained as minimizers of certain estimates of the mean integrated
      squared error (MISE). It is shown that the smoothed bootstrap offers a motivation
      for choosing the proposed MISE estimates for minimization. The efficacy of the
      proposed procedures is investigated through simulation studies and some
      illustrations are provided.

PMID- 19156189
TI  - Revisiting the Hirao Cross-coupling: Improved Synthesis of Aryl and Heteroaryl
      Phosphonates.
AB  - The palladium-catalyzed cross-coupling of dialkylphosphite with aromatic
      electrophiles (Hirao coupling) was re-investigated. Some limitations in terms of
      palladium loadings and substrate reactivity are alleviated with the use of
      Pd(OAc)(2) complexed to 1,1'-bis(diphenylphosphino)ferrocene (dppf) as a ligand.
      Various aryl and heteroaryl halides are employed to deliver both known and novel
      substituted phosphonates. The first examples of aryl chloride couplings are also
      reported.

PMID- 19156190
TI  - Cost-effectiveness of chagas disease vector control strategies in Northwestern
      Argentina.
AB  - BACKGROUND: Control and prevention of Chagas disease rely mostly on residual
      spraying of insecticides. In Argentina, vector control shifted from a vertical to
      a fully horizontal strategy based on community participation between 1992 and
      2004. The effects of such strategy on Triatoma infestans, the main domestic
      vector, and on disease transmission have not been assessed. METHODS AND FINDINGS:
      Based on retrospective (1993-2004) records from the Argentinean Ministry of
      Health for the Moreno Department, Northwestern Argentina, we performed a cost
      effectiveness (CE) analysis and compared the observed CE of the fully horizontal
      vector control strategy with the expected CE for a vertical or a mixed (i.e.,
      vertical attack phase followed by horizontal surveillance) strategy. Total direct
      costs (in 2004 US$) of the horizontal and mixed strategies were, respectively,
      3.3 and 1.7 times lower than the costs of the vertical strategy, due to
      reductions in personnel costs. The estimated CE ratios for the vertical, mixed
      and horizontal strategies were US$132, US$82 and US$45 per averted human case,
      respectively. When per diems were excluded from the costs (i.e., simulating the
      decentralization of control activities), the CE of vertical, mixed and horizontal
      strategies was reduced to US$60, US$42 and US$32 per averted case, respectively.
      CONCLUSIONS AND SIGNIFICANCE: The mixed strategy would have averted between 1.6
      and 4.0 times more human cases than the fully horizontal strategy, and would have
      been the most cost-effective option to interrupt parasite transmission in the
      Department. In rural and dispersed areas where waning vertical vector programs
      cannot accomplish full insecticide coverage, alternative strategies need to be
      developed. If properly implemented, community participation represents not only
      the most appealing but also the most cost-effective alternative to accomplish
      such objectives.

PMID- 19156191
TI  - A new PCR-based approach indicates the range of Clonorchis sinensis now extends
      to Central Thailand.
AB  - Differentiation of the fish-borne trematodes belonging to the Opisthorchiidae,
      Heterophyidae and Lecithodendriidae is important from a clinical and
      epidemiological perspective, yet it is impossible to do using conventional
      coprological techniques, as the eggs are morphologically similar. Epidemiological
      investigation therefore currently relies on morphological examination of adult
      worms following expulsion chemotherapy. A PCR test capable of amplifying a
      segment of the internal transcribed spacer region of ribosomal DNA for the
      opisthorchiid and heterophyid flukes eggs taken directly from faeces was
      developed and evaluated in a rural community in central Thailand. The lowest
      quantity of DNA that could be amplified from individual adults of Opisthorchis
      viverrini, Clonorchis sinensis and Haplorchis taichui was estimated at 0.6 pg,
      0.8 pg and 3 pg, respectively. The PCR was capable of detecting mixed infection
      with the aforementioned species of flukes under experimental conditions. A total
      of 11.6% of individuals in rural communities in Sanamchaikaet district, central
      Thailand, were positive for 'Opisthorchis-like' eggs in their faeces using
      conventional parasitological detection techniques. In comparison to microscopy,
      the PCR yielded a sensitivity and specificity of 71.0% and 76.7%, respectively.
      Analysis of the microscopy-positive PCR products revealed 64% and 23% of
      individuals to be infected with O. viverrini and C. sinensis, respectively. The
      remaining 13% (three individuals) were identified as eggs of Didymozoidae,
      presumably being passed mechanically in the faeces following the ingestion of
      infected fishes. An immediate finding of this study is the identification and
      first report of a C. sinensis-endemic community in central Thailand. This extends
      the known range of this liver fluke in Southeast Asia. The PCR developed herein
      provides an important tool for the specific identification of liver and
      intestinal fluke species for future epidemiological surveys.

PMID- 19156192
TI  - Diagnostic accuracy of NS1 ELISA and lateral flow rapid tests for dengue
      sensitivity, specificity and relationship to viraemia and antibody responses.
AB  - BACKGROUND: Dengue is a public health problem in many countries. Rapid diagnosis
      of dengue can assist patient triage and management. Detection of the dengue viral
      protein, NS1, represents a new approach to dengue diagnosis.
      METHODOLOGY/PRINCIPAL FINDINGS: The sensitivity and specificity of the Platelia
      NS1 ELISA assay and an NS1 lateral flow rapid test (LFRT) were compared against a
      gold standard reference diagnostic algorithm in 138 Vietnamese children and
      adults. Overall, the Platelia NS1 ELISA was modestly more sensitive (82%) than
      the NS1 LFRT (72%) in confirmed dengue cases. Both ELISA and LFRT assays were
      more sensitive for primary than secondary dengue, and for specimens collected
      within 3 days of illness onset relative to later time points. The presence of
      measurable DENV-reactive IgG and to a lesser extent IgM in the test sample was
      associated with a significantly lower rate of NS1 detection in both assays. NS1
      positivity was associated with the underlying viraemia, as NS1-positive samples
      had a significantly higher viraemia than NS1-negative samples matched for
      duration of illness. The Platelia and NS1 LFRT were 100% specific, being negative
      in all febrile patients without evidence of recent dengue, as well as in patients
      with enteric fever, malaria, Japanese encephalitis and leptospirosis.
      CONCLUSIONS/SIGNIFICANCE: Collectively, these data suggest NS1 assays deserve
      inclusion in the diagnostic evaluation of dengue patients, but with due
      consideration for the limitations in patients who present late in their illness
      or have a concomitant humoral immune response.

PMID- 19156193
TI  - Prevalence distribution and risk factors for Schistosoma hematobium infection
      among school children in Blantyre, Malawi.
AB  - BACKGROUND: Schistosomiasis is a public health problem in Malawi but estimates of
      its prevalence vary widely. There is need for updated information on the extent
      of disease burden, communities at risk and factors associated with infection at
      the district and sub-district level to facilitate effective prioritization and
      monitoring while ensuring ownership and sustainability of prevention and control
      programs at the local level. METHODS AND FINDINGS: We conducted a cross-sectional
      study between May and July 2006 among pupils in Blantyre district from a
      stratified random sample of 23 primary schools. Information on socio-demographic
      factors, schistosomiasis symptoms and other risk factors was obtained using
      questionnaires. Urine samples were examined for Schistosoma hematobium ova using
      filtration method. Bivariate and multiple logistic regressions with robust
      estimates were used to assess risk factors for S. hematobium. One thousand one
      hundred and fifty (1,150) pupils were enrolled with a mean age of 10.5 years and
      51.5% of them were boys. One thousand one hundred and thirty-nine (1,139) pupils
      submitted urine and S. hematobium ova were detected in 10.4% (95%CI 5.43-15.41%).
      Male gender (OR 1.81; 95% CI 1.06-3.07), child's knowledge of an existing open
      water source (includes river, dam, springs, lake, etc.) in the area (OR 1.90; 95%
      CI 1.14-3.46), history of urinary schistosomiasis in the past month (OR 3.65; 95%
      CI 2.22-6.00), distance of less than 1 km from school to the nearest open water
      source (OR 5.39; 95% CI 1.67-17.42) and age 8-10 years (OR 4.55; 95% CI 1.53
      13.50) compared to those 14 years or older were associated with infection. Using
      urine microscopy as a gold standard, the sensitivity and specificity of self
      reported hematuria was 68.3% and 73.6%, respectively. However, the positive
      predictive value was low at 23.9% and was associated with age. CONCLUSION: The
      study provides an important update on the status of infection in this part of sub
      Saharan Africa and exemplifies the success of deliberate national efforts to
      advance active participation in schistosomiasis prevention and control activities
      at the sub-national or sub-district levels. In this population, children who
      attend schools close to open water sources are at an increased risk of infection
      and self-reported hematuria may still be useful in older children in this region.

PMID- 19156194
TI  - Cranial osteogenesis and suture morphology in Xenopus laevis: a unique model
      system for studying craniofacial development.
AB  - BACKGROUND: The tremendous diversity in vertebrate skull formation illustrates
      the range of forms and functions generated by varying genetic programs.
      Understanding the molecular basis for this variety may provide us with insights
      into mechanisms underlying human craniofacial anomalies. In this study, we
      provide evidence that the anuran Xenopus laevis can be developed as a simplified
      model system for the study of cranial ossification and suture patterning. The
      head structures of Xenopus undergo dramatic remodelling during metamorphosis; as
      a result, tadpole morphology differs greatly from the adult bony skull. Because
      of the extended larval period in Xenopus, the molecular basis of these
      alterations has not been well studied. METHODOLOGY/PRINCIPAL FINDINGS: We
      examined late larval, metamorphosing, and post-metamorphosis froglet stages in
      intact and sectioned animals. Using micro-computed tomography (microCT) and
      tissue staining of the frontoparietal bone and surrounding cartilage, we observed
      that bone formation initiates from lateral ossification centers, proceeding from
      posterior-to-anterior. Histological analyses revealed midline abutting and
      posterior overlapping sutures. To determine the mechanisms underlying the large
      scale cranial changes, we examined proliferation, apoptosis, and proteinase
      activity during remodelling of the skull roof. We found that tissue turnover
      during metamorphosis could be accounted for by abundant matrix metalloproteinase
      (MMP) activity, at least in part by MMP-1 and -13. CONCLUSION: A better
      understanding of the dramatic transformation from cartilaginous head structures
      to bony skull during Xenopus metamorphosis may provide insights into tissue
      remodelling and regeneration in other systems. Our studies provide some new
      molecular insights into this process.

PMID- 19156195
TI  - Secretion of hepatitis C virus envelope glycoproteins depends on assembly of
      apolipoprotein B positive lipoproteins.
AB  - The density of circulating hepatitis C virus (HCV) particles in the blood of
      chronically infected patients is very heterogeneous. The very low density of some
      particles has been attributed to an association of the virus with apolipoprotein
      B (apoB) positive and triglyceride rich lipoproteins (TRL) likely resulting in
      hybrid lipoproteins known as lipo-viro-particles (LVP) containing the viral
      envelope glycoproteins E1 and E2, capsid and viral RNA. The specific infectivity
      of these particles has been shown to be higher than the infectivity of particles
      of higher density. The nature of the association of HCV particles with
      lipoproteins remains elusive and the role of apolipoproteins in the synthesis and
      assembly of the viral particles is unknown. The human intestinal Caco-2 cell line
      differentiates in vitro into polarized and apoB secreting cells during asymmetric
      culture on porous filters. By using this cell culture system, cells stably
      expressing E1 and E2 secreted the glycoproteins into the basal culture medium
      after one week of differentiation concomitantly with TRL secretion. Secreted
      glycoproteins were only detected in apoB containing density fractions. The E1-E2
      and apoB containing particles were unique complexes bearing the envelope
      glycoproteins at their surface since apoB could be co-immunoprecipitated with E2
      specific antibodies. Envelope protein secretion was reduced by inhibiting the
      lipidation of apoB with an inhibitor of the microsomal triglyceride transfer
      protein. HCV glycoproteins were similarly secreted in association with TRL from
      the human liver cell line HepG2 but not by Huh-7 and Huh-7.5 hepatoma cells that
      proved deficient for lipoprotein assembly. These data indicate that HCV envelope
      glycoproteins have the intrinsic capacity to utilize apoB synthesis and
      lipoprotein assembly machinery even in the absence of the other HCV proteins. A
      model for LVP assembly is proposed.

PMID- 19156196
TI  - Alternative complement activity in the egg cytosol of amphioxus Branchiostoma
      belcheri: evidence for the defense role of maternal complement components.
AB  - BACKGROUND: The eggs in most invertebrates are fertilized externally, and
      therefore their resulting embryos are exposed to an environment full of microbes,
      many of which are pathogens capable of killing other organisms. How the
      developing embryos of invertebrates defend themselves against pathogenic attacks
      is an intriguing question to biologists, and remains largely unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we clearly demonstrated that the egg cytosol
      prepared from the newly fertilized eggs of amphioxus Branchiostoma belcheri, an
      invertebrate chordate, was able to inhibit the growth of both the Gram-negative
      bacterium Vibrio anguillarum and the Gram-positive bacterium Staphylococcus
      aureus. All findings point to that it is the complement system operating via the
      alternative pathway that is attributable to the bacteriostatic activity.
      CONCLUSIONS/SIGNIFICANCE: This appears to be the first report providing the
      evidence for the functional role of the maternal complement components in the
      eggs of invertebrate species, paving the way for the study of maternal immunity
      in other invertebrate organisms whose eggs are fertilized in vitro. It also
      supports the notion that the early developing embryos share some defense
      mechanisms common with the adult species.

PMID- 19156197
TI  - Discovery of a novel activator of KCNQ1-KCNE1 K channel complexes.
AB  - KCNQ1 voltage-gated K(+) channels (Kv7.1) associate with the family of five KCNE
      peptides to form complexes with diverse gating properties and pharmacological
      sensitivities. The varied gating properties of the different KCNQ1-KCNE complexes
      enables the same K(+) channel to function in both excitable and non excitable
      tissues. Small molecule activators would be valuable tools for dissecting the
      gating mechanisms of KCNQ1-KCNE complexes; however, there are very few known
      activators of KCNQ1 channels and most are ineffective on the physiologically
      relevant KCNQ1-KCNE complexes. Here we show that a simple boronic acid,
      phenylboronic acid (PBA), activates KCNQ1/KCNE1 complexes co-expressed in Xenopus
      oocytes at millimolar concentrations. PBA shifts the voltage sensitivity of KCNQ1
      channel complexes to favor the open state at negative potentials. Analysis of
      different-sized charge carriers revealed that PBA also targets the permeation
      pathway of KCNQ1 channels. Activation by the boronic acid moiety has some
      specificity for the Kv7 family members (KCNQ1, KCNQ2/3, and KCNQ4) since PBA does
      not activate Shaker or hERG channels. Furthermore, the commercial availability of
      numerous PBA derivatives provides a large class of compounds to investigate the
      gating mechanisms of KCNQ1-KCNE complexes.

PMID- 19156198
TI  - Circulating lipoproteins are a crucial component of host defense against invasive
      Salmonella typhimurium infection.
AB  - BACKGROUND: Circulating lipoproteins improve the outcome of severe Gram-negative
      infections through neutralizing lipopolysaccharides (LPS), thus inhibiting the
      release of proinflammatory cytokines. METHODS/PRINCIPAL FINDINGS: Low density
      lipoprotein receptor deficient (LDLR-/-) mice, with a 7-fold increase in LDL, are
      resistant against infection with Salmonella typhimurium (survival 100% vs 5%,
      p<0.001), and 100 to 1000-fold lower bacterial burden in the organs, compared
      with LDLR+/+ mice. Protection was not due to differences in cytokine production,
      phagocytosis, and killing of Salmonella organisms. The differences were caused by
      the excess of lipoproteins, as hyperlipoproteinemic ApoE-/- mice were also highly
      resistant to Salmonella infection. Lipoproteins protect against infection by
      interfering with the binding of Salmonella to host cells, and preventing organ
      invasion. This leads to an altered biodistribution of the microorganisms during
      the first hours of infection: after intravenous injection of Salmonella into
      LDLR+/+ mice, the bacteria invaded the liver and spleen within 30 minutes of
      infection. In contrast, in LDLR-/- mice, Salmonella remained constrained to the
      circulation from where they were efficiently cleared, with decreased organ
      invasion. CONCLUSIONS: plasma lipoproteins are a potent host defense mechanism
      against invasive Salmonella infection, by blocking adhesion of Salmonella to the
      host cells and subsequent tissue invasion.

PMID- 19156199
TI  - cGMP-dependent protein kinase type I is implicated in the regulation of the
      timing and quality of sleep and wakefulness.
AB  - Many effects of nitric oxide (NO) are mediated by the activation of guanylyl
      cyclases and subsequent production of the second messenger cyclic guanosine-3',5'
      monophosphate (cGMP). cGMP activates cGMP-dependent protein kinases (PRKGs),
      which can therefore be considered downstream effectors of NO signaling. Since NO
      is thought to be involved in the regulation of both sleep and circadian rhythms,
      we analyzed these two processes in mice deficient for cGMP-dependent protein
      kinase type I (PRKG1) in the brain. Prkg1 mutant mice showed a strikingly altered
      distribution of sleep and wakefulness over the 24 hours of a day as well as
      reductions in rapid-eye-movement sleep (REMS) duration and in non-REM sleep
      (NREMS) consolidation, and their ability to sustain waking episodes was
      compromised. Furthermore, they displayed a drastic decrease in
      electroencephalogram (EEG) power in the delta frequency range (1-4 Hz) under
      baseline conditions, which could be normalized after sleep deprivation. In line
      with the re-distribution of sleep and wakefulness, the analysis of wheel-running
      and drinking activity revealed more rest bouts during the activity phase and a
      higher percentage of daytime activity in mutant animals. No changes were observed
      in internal period length and phase-shifting properties of the circadian clock
      while chi-squared periodogram amplitude was significantly reduced, hinting at a
      less robust oscillator. These results indicate that PRKG1 might be involved in
      the stabilization and output strength of the circadian oscillator in mice.
      Moreover, PRKG1 deficiency results in an aberrant pattern, and consequently a
      reduced quality, of sleep and wakefulness, possibly due to a decreased wake
      promoting output of the circadian system impinging upon sleep.

PMID- 19156200
TI  - Landscape changes influence the occurrence of the melioidosis bacterium
      Burkholderia pseudomallei in soil in northern Australia.
AB  - BACKGROUND: The soil-dwelling saprophyte bacterium Burkholderia pseudomallei is
      the cause of melioidosis, a severe disease of humans and animals in southeast
      Asia and northern Australia. Despite the detection of B. pseudomallei in various
      soil and water samples from endemic areas, the environmental habitat of B.
      pseudomallei remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: We performed a
      large survey in the Darwin area in tropical Australia and screened 809 soil
      samples for the presence of these bacteria. B. pseudomallei were detected by
      using a recently developed and validated protocol involving soil DNA extraction
      and real-time PCR targeting the B. pseudomallei-specific Type III Secretion
      System TTS1 gene cluster. Statistical analyses such as multivariable cluster
      logistic regression and principal component analysis were performed to assess the
      association of B. pseudomallei with environmental factors. The combination of
      factors describing the habitat of B. pseudomallei differed between undisturbed
      sites and environmentally manipulated areas. At undisturbed sites, the occurrence
      of B. pseudomallei was found to be significantly associated with areas rich in
      grasses, whereas at environmentally disturbed sites, B. pseudomallei was
      associated with the presence of livestock animals, lower soil pH and different
      combinations of soil texture and colour. CONCLUSIONS/SIGNIFICANCE: This study
      contributes to the elucidation of environmental factors influencing the
      occurrence of B. pseudomallei and raises concerns that B. pseudomallei may spread
      due to changes in land use.

PMID- 19156201
TI  - Antimicrobial peptide evolution in the Asiatic honey bee Apis cerana.
AB  - The Asiatic honeybee, Apis cerana Fabricius, is an important honeybee species in
      Asian countries. It is still found in the wild, but is also one of the few bee
      species that can be domesticated. It has acquired some genetic advantages and
      significantly different biological characteristics compared with other Apis
      species. However, it has been less studied, and over the past two decades, has
      become a threatened species in China. We designed primers for the sequences of
      the four antimicrobial peptide cDNA gene families (abaecin, defensin, apidaecin,
      and hymenoptaecin) of the Western honeybee, Apis mellifera L. and identified all
      the antimicrobial peptide cDNA genes in the Asiatic honeybee for the first time.
      All the sequences were amplified by reverse transcriptase-polymerase chain
      reaction (RT-PCR). In all, 29 different defensin cDNA genes coding 7 different
      defensin peptides, 11 different abaecin cDNA genes coding 2 different abaecin
      peptides, 13 different apidaecin cDNA genes coding 4 apidaecin peptides and 34
      different hymenoptaecin cDNA genes coding 13 different hymenoptaecin peptides
      were cloned and identified from the Asiatic honeybee adult workers. Detailed
      comparison of these four antimicrobial peptide gene families with those of the
      Western honeybee revealed that there are many similarities in the quantity and
      amino acid components of peptides in the abaecin, defensin and apidaecin
      families, while many more hymenoptaecin peptides are found in the Asiatic
      honeybee than those in the Western honeybee (13 versus 1). The results indicated
      that the Asiatic honeybee adult generated more variable antimicrobial peptides,
      especially hymenoptaecin peptides than the Western honeybee when stimulated by
      pathogens or injury. This suggests that, compared to the Western honeybee that
      has a longer history of domestication, selection on the Asiatic honeybee has
      favored the generation of more variable antimicrobial peptides as protection
      against pathogens.

PMID- 19156202
TI  - Imaging of Streptomyces coelicolor A3(2) with reduced autofluorescence reveals a
      novel stage of FtsZ localization.
AB  - Imaging of low abundance proteins in time and space by fluorescence microscopy is
      typically hampered by host-cell autofluorescence. Streptomycetes are an important
      model system for the study of bacterial development, and undergo multiple
      synchronous cell division during the sporulation stage. To analyse this
      phenomenon in detail, fluorescence microscopy, and in particular also the
      recently published novel live imaging techniques, require optimal signal to noise
      ratios. Here we describe the development of a novel derivative of Streptomyces
      coelicolor A3(2) with strongly reduced autofluorescence, allowing the imaging of
      fluorescently labelled proteins at significantly higher resolution. The enhanced
      image detail provided novel localization information for the cell division
      protein FtsZ, demonstrating a new developmental stage where multiple FtsZ foci
      accumulate at the septal plane. This suggests that multiple foci are sequentially
      produced, ultimately connecting to form the complete Z ring. The enhanced imaging
      properties are an important step forward for the confocal and live imaging of
      less abundant proteins and for the use of lower intensity fluorophores in
      streptomycetes.

PMID- 19156203
TI  - Conidiation color mutants of Aspergillus fumigatus are highly pathogenic to the
      heterologous insect host Galleria mellonella.
AB  - The greater wax moth Galleria mellonella has been widely used as a heterologous
      host for a number of fungal pathogens including Candida albicans and Cryptococcus
      neoformans. A positive correlation in pathogenicity of these yeasts in this
      insect model and animal models has been observed. However, very few studies have
      evaluated the possibility of applying this heterologous insect model to
      investigate virulence traits of the filamentous fungal pathogen Aspergillus
      fumigatus, the leading cause of invasive aspergillosis. Here, we have examined
      the impact of mutations in genes involved in melanin biosynthesis on the
      pathogenicity of A. fumigatus in the G. mellonella model. Melanization in A.
      fumigatus confers bluish-grey color to conidia and is a known virulence factor in
      mammal models. Surprisingly, conidial color mutants in B5233 background that have
      deletions in the defined six-gene cluster required for DHN-melanin biosynthesis
      caused enhanced insect mortality compared to the parent strain. To further
      examine and confirm the relationship between melanization defects and enhanced
      virulence in the wax moth model, we performed random insertional mutagenesis in
      the Af293 genetic background to isolate mutants producing altered conidia colors.
      Strains producing conidia of previously identified colors and of novel colors
      were isolated. Interestingly, these color mutants displayed a higher level of
      pathogenicity in the insect model compared to the wild type. Although some of the
      more virulent color mutants showed increased resistance to hydrogen peroxide,
      overall phenotypic characterizations including secondary metabolite production,
      metalloproteinase activity, and germination rate did not reveal a general
      mechanism accountable for the enhanced virulence of these color mutants observed
      in the insect model. Our observations indicate instead, that exacerbated immune
      response of the wax moth induced by increased exposure of PAMPs (pathogen
      associated molecular patterns) may cause self-damage that results in increased
      mortality of larvae infected with the color mutants. The current study
      underscores the limitations of using this insect model for inferring the
      pathogenic potential of A. fumigatus strains in mammals, but also points to the
      importance of understanding the innate immunity of the insect host in providing
      insights into the pathogenicity level of different fungal strains in this model.
      Additionally, our observations that melanization defective color mutants
      demonstrate increased virulence in the insect wax moth, suggest the potential of
      using melanization defective mutants of native insect fungal pathogens in the
      biological control of insect populations.

PMID- 19156204
TI  - IL-1beta, IL-6, and RANTES as biomarkers of Chikungunya severity.
AB  - BACKGROUND: Little is known about the immunopathogenesis of Chikungunya virus.
      Circulating levels of immune mediators and growth factors were analyzed from
      patients infected during the first Singaporean Chikungunya fever outbreak in
      early 2008 to establish biomarkers associated with infection and/or disease
      severity. METHODS AND FINDINGS: Adult patients with laboratory-confirmed
      Chikungunya fever infection, who were referred to the Communicable Disease
      Centre/Tan Tock Seng Hospital during the period from January to February 2008,
      were included in this retrospective study. Plasma fractions were analyzed using a
      multiplex-microbead immunoassay. Among the patients, the most common clinical
      features were fever (100%), arthralgia (90%), rash (50%) and conjunctivitis
      (40%). Profiles of 30 cytokines, chemokines, and growth factors were able to
      discriminate the clinical forms of Chikungunya from healthy controls, with
      patients classified as non-severe and severe disease. Levels of 8 plasma
      cytokines and 4 growth factors were significantly elevated. Statistical analysis
      showed that an increase in IL-1beta, IL-6 and a decrease in RANTES were
      associated with disease severity. CONCLUSIONS: This is the first comprehensive
      report on the production of cytokines, chemokines, and growth factors during
      acute Chikungunya virus infection. Using these biomarkers, we were able to
      distinguish between mild disease and more severe forms of Chikungunya fever, thus
      enabling the identification of patients with poor prognosis and monitoring of the
      disease.

PMID- 19156205
TI  - Direct metagenomic detection of viral pathogens in nasal and fecal specimens
      using an unbiased high-throughput sequencing approach.
AB  - With the severe acute respiratory syndrome epidemic of 2003 and renewed attention
      on avian influenza viral pandemics, new surveillance systems are needed for the
      earlier detection of emerging infectious diseases. We applied a "next-generation"
      parallel sequencing platform for viral detection in nasopharyngeal and fecal
      samples collected during seasonal influenza virus (Flu) infections and norovirus
      outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to
      amplify RNA extracted from 0.1-0.25 ml of nasopharyngeal aspirates (N = 3) and
      fecal specimens (N = 5), and more than 10 microg of cDNA was synthesized.
      Unbiased high-throughput sequencing of these 8 samples yielded 15,298-32,335
      (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although
      whole genome analysis was not available because the majority (>90%) of reads were
      host genome-derived, 20-460 Flu-reads were detected, which was sufficient for
      subtype identification. In fecal samples, bacteria and host cells were removed by
      centrifugation, resulting in gain of 484-15,260 reads of norovirus sequence (78
      98% of the whole genome was covered), except for one specimen that was under
      detectable by RT-PCR. These results suggest that our unbiased high-throughput
      sequencing approach is useful for directly detecting pathogenic viruses without
      advance genetic information. Although its cost and technological availability
      make it unlikely that this system will very soon be the diagnostic standard
      worldwide, this system could be useful for the earlier discovery of novel
      emerging viruses and bioterrorism, which are difficult to detect with
      conventional procedures.

PMID- 19156206
TI  - Impact of HIV infection and Kaposi sarcoma on human herpesvirus-8 mucosal
      replication and dissemination in Uganda.
AB  - INTRODUCTION: Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and
      occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is
      important both in transmission of HHV-8 and progression to KS. We characterized
      the sites and frequency of HHV-8 detection in Ugandans with and without HIV and
      KS. METHODS: Participants were enrolled into one of four groups on the basis of
      HIV and KS status (HIV negative/KS negative, HIV positive/KS negative, HIV
      negative/KS positive, and HIV positive/KS positive). Participants collected oral
      swabs daily and clinicians collected oral swabs, anogenital swabs, and plasma
      samples weekly over 4 weeks. HHV-8 DNA at each site was quantified by polymerase
      chain reaction (PCR). RESULTS: 78 participants collected a total of 2063 orals
      swabs and 358 plasma samples. Of these, 428 (21%) oral swabs and 96 (27%) plasma
      samples had detectable HHV-8 DNA. HHV-8 was detected more frequently in both the
      oropharynx of persons with KS (24 (57%) of 42 persons with KS vs. 8 (22%) of 36
      persons without, p = 0.002) and the peripheral blood (30 (71%) of 42 persons with
      KS vs. 8 (22%) of 36 persons without, p<0.001). In a multivariate model, HHV-8
      viremia was more frequent among men (IRR = 3.3, 95% CI = 1.7-6.2, p<0.001),
      persons with KS (IRR = 3.9, 95% CI = 1.7-9.0, p = 0.001) and persons with HIV
      infection (IRR = 1.7, 95% CI = 1.0-2.7, p = 0.03). Importantly, oral HHV-8
      detection predicted the subsequent HHV-8 viremia. HHV-8 viremia was significantly
      more common when HHV-8 DNA was detected from the oropharynx during the week prior
      than when oral HHV-8 was not detected (RR = 3.3, 95% CI = 1.8-5.9 p<0.001).
      Genital HHV-8 detection was rare (9 (3%) of 272 swabs). CONCLUSIONS: HHV-8
      detection is frequent in the oropharynx and peripheral blood of Ugandans with
      endemic and epidemic KS. Replication at these sites is highly correlated, and
      viremia is increased in men and those with HIV. The high incidence of HHV-8
      replication at multiple anatomic sites may be an important factor leading to and
      sustaining the high prevalence of KS in Uganda.

PMID- 19156207
TI  - Sensitive and specific detection of the non-human sialic Acid N
      glycolylneuraminic acid in human tissues and biotherapeutic products.
AB  - BACKGROUND: Humans are genetically defective in synthesizing the common mammalian
      sialic acid N-glycolylneuraminic acid (Neu5Gc), but can metabolically incorporate
      it from dietary sources (particularly red meat and milk) into glycoproteins and
      glycolipids of human tumors, fetuses and some normal tissues. Metabolic
      incorporation of Neu5Gc from animal-derived cells and medium components also
      results in variable contamination of molecules and cells intended for human
      therapies. These Neu5Gc-incorporation phenomena are practically significant,
      because normal humans can have high levels of circulating anti-Neu5Gc antibodies.
      Thus, there is need for the sensitive and specific detection of Neu5Gc in human
      tissues and biotherapeutic products. Unlike monoclonal antibodies that recognize
      Neu5Gc only in the context of underlying structures, chicken immunoglobulin Y
      (IgY) polyclonal antibodies can recognize Neu5Gc in broader contexts. However,
      prior preparations of such antibodies (including our own) suffered from some non
      specificity, as well as some cross-reactivity with the human sialic acid N
      acetylneuraminic acid (Neu5Ac). METHODOLOGY/PRINCIPAL FINDINGS: We have developed
      a novel affinity method utilizing sequential columns of immobilized human and
      chimpanzee serum sialoglycoproteins, followed by specific elution from the latter
      column by free Neu5Gc. The resulting mono-specific antibody shows no staining in
      tissues or cells from mice with a human-like defect in Neu5Gc production. It
      allows sensitive and specific detection of Neu5Gc in all underlying glycan
      structural contexts studied, and is applicable to immunohistochemical, enzyme
      linked immunosorbent assay (ELISA), Western blot and flow cytometry analyses. Non
      immune chicken IgY is used as a reliable negative control. We show that these
      approaches allow sensitive detection of Neu5Gc in human tissue samples and in
      some biotherapeutic products, and finally show an example of how Neu5Gc might be
      eliminated from such products, by using a human cell line grown under defined
      conditions. CONCLUSIONS: We report a reliable antibody-based method for highly
      sensitive and specific detection of the non-human sialic acid Neu5Gc in human
      tissues and biotherapeutic products that has not been previously described.

PMID- 19156208
TI  - Are Hox genes ancestrally involved in axial patterning? Evidence from the
      hydrozoan Clytia hemisphaerica (Cnidaria).
AB  - BACKGROUND: The early evolution and diversification of Hox-related genes in
      eumetazoans has been the subject of conflicting hypotheses concerning the
      evolutionary conservation of their role in axial patterning and the pre
      bilaterian origin of the Hox and ParaHox clusters. The diversification of
      Hox/ParaHox genes clearly predates the origin of bilaterians. However, the
      existence of a "Hox code" predating the cnidarian-bilaterian ancestor and
      supporting the deep homology of axes is more controversial. This assumption was
      mainly based on the interpretation of Hox expression data from the sea anemone,
      but growing evidence from other cnidarian taxa puts into question this
      hypothesis. METHODOLOGY/PRINCIPAL FINDINGS: Hox, ParaHox and Hox-related genes
      have been investigated here by phylogenetic analysis and in situ hybridisation in
      Clytia hemisphaerica, an hydrozoan species with medusa and polyp stages
      alternating in the life cycle. Our phylogenetic analyses do not support an origin
      of ParaHox and Hox genes by duplication of an ancestral ProtoHox cluster, and
      reveal a diversification of the cnidarian HOX9-14 genes into three groups called
      A, B, C. Among the 7 examined genes, only those belonging to the HOX9-14 and the
      CDX groups exhibit a restricted expression along the oral-aboral axis during
      development and in the planula larva, while the others are expressed in very
      specialised areas at the medusa stage. CONCLUSIONS/SIGNIFICANCE: Cross species
      comparison reveals a strong variability of gene expression along the oral-aboral
      axis and during the life cycle among cnidarian lineages. The most parsimonious
      interpretation is that the Hox code, collinearity and conservative role along the
      antero-posterior axis are bilaterian innovations.

PMID- 19156209
TI  - Proteomic-based detection of a protein cluster dysregulated during cardiovascular
      development identifies biomarkers of congenital heart defects.
AB  - BACKGROUND: Cardiovascular development is vital for embryonic survival and
      growth. Early gestation embryo loss or malformation has been linked to yolk sac
      vasculopathy and congenital heart defects (CHDs). However, the molecular pathways
      that underlie these structural defects in humans remain largely unknown hindering
      the development of molecular-based diagnostic tools and novel therapies.
      METHODOLOGY/PRINCIPAL FINDINGS: Murine embryos were exposed to high glucose, a
      condition known to induce cardiovascular defects in both animal models and
      humans. We further employed a mass spectrometry-based proteomics approach to
      identify proteins differentially expressed in embryos with defects from those
      with normal cardiovascular development. The proteins detected by mass
      spectrometry (WNT16, ST14, Pcsk1, Jumonji, Morca2a, TRPC5, and others) were
      validated by Western blotting and immunoflorescent staining of the yolk sac and
      heart. The proteins within the proteomic dataset clustered to adhesion/migration,
      differentiation, transport, and insulin signaling pathways. A functional role for
      several proteins (WNT16, ADAM15 and NOGO-A/B) was demonstrated in an ex vivo
      model of heart development. Additionally, a successful application of a cluster
      of protein biomarkers (WNT16, ST14 and Pcsk1) as a prenatal screen for CHDs was
      confirmed in a study of human amniotic fluid (AF) samples from women carrying
      normal fetuses and those with CHDs. CONCLUSIONS/SIGNIFICANCE: The novel finding
      that WNT16, ST14 and Pcsk1 protein levels increase in fetuses with CHDs suggests
      that these proteins may play a role in the etiology of human CHDs. The
      information gained through this bed-side to bench translational approach
      contributes to a more complete understanding of the protein pathways dysregulated
      during cardiovascular development and provides novel avenues for diagnostic and
      therapeutic interventions, beneficial to fetuses at risk for CHDs.

PMID- 19156210
TI  - Full sequence and comparative analysis of the plasmid pAPEC-1 of avian pathogenic
      E. coli chi7122 (O78:K80:H9).
AB  - BACKGROUND: Extra-intestinal pathogenic E. coli (ExPEC), including Avian
      Pathogenic E. coli (APEC), are very diverse. They cause a complex of diseases in
      Human, animals, and birds. Even though large plasmids are often associated with
      the virulence of ExPEC, their characterization is still in its infancy.
      METHODOLOGY/PRINCIPAL FINDINGS: We fully sequenced and analyzed the large plasmid
      pAPEC-1 (103,275-bp) associated with the APEC strain chi7122, from worldwide
      serogroup O78ratioK80ratioH9. A putative virulence region spanning an 80-kb
      region of pAPEC-1 possesses four iron acquisition systems (iutA iucABCD, sitABCD,
      iroBCDN, and temperature-sensitive hemagglutinin tsh), a colicin V operon,
      increasing serum sensitivity iss, ompT, hlyF, and etsABC. Thirty three ORFs in
      pAPEC-1 are identified as insertion sequences (ISs) that belong to nine families
      with diverse origins. The full length of the transfer region in pAPEC-1 (11 kb)
      is shorter compared to the tra region of other sequenced F plasmids; the absence
      of some tra genes in pAPEC-1 affects its self-transferability, and the
      conjugative function of the plasmid was effective only in the presence of other
      plasmids. Two-replicon systems, repFIIA-repFIC and repFIB, and two post
      segregational systems, srnB and hok/sok, are also present in the sequence of
      pAPEC-1. The comparison of the pAPEC-1 sequence with the two available plasmid
      sequences reveals more gene loss and reorganization than previously appreciated.
      The presence of pAPEC-1-associated genes is assessed in human ExPEC by PCR. Many
      patterns of association between genes are found. CONCLUSIONS/SIGNIFICANCE: The
      pathotype typical of pAPEC-1 was present in some human strains, which indicates a
      horizontal transfer between strains and the zoonotic risk of APEC strains. ColV
      plasmids could have common virulence genes that could be acquired by
      transposition, without sharing genes of plasmid function.

PMID- 19156212
TI  - Preparing the perfect cuttlefish meal: complex prey handling by dolphins.
AB  - Dolphins are well known for their complex social and foraging behaviours. Direct
      underwater observations of wild dolphin feeding behaviour however are rare. At
      mass spawning aggregations of giant cuttlefish (Sepia apama) in the Upper Spencer
      Gulf in South Australia, a wild female Indo-Pacific bottlenose dolphin (Tursiops
      aduncus) was observed and recorded repeatedly catching, killing and preparing
      cuttlefish for consumption using a specific and ordered sequence of behaviours.
      Cuttlefish were herded to a sand substrate, pinned to the seafloor, killed by
      downward thrust, raised mid-water and beaten by the dolphin with its snout until
      the ink was released and drained. The deceased cuttlefish was then returned to
      the seafloor, inverted and forced along the sand substrate in order to strip the
      thin dorsal layer of skin off the mantle, thus releasing the buoyant calcareous
      cuttlebone. This stepped behavioural sequence significantly improves prey quality
      through 1) removal of the ink (with constituent melanin and tyrosine), and 2) the
      calcareous cuttlebone. Observations of foraging dolphin pods from above-water at
      this site (including the surfacing of intact clean cuttlebones) suggest that some
      or all of this prey handling sequence may be used widely by dolphins in the
      region. Aspects of the unique mass spawning aggregations of giant cuttlefish in
      this region of South Australia may have contributed to the evolution of this
      behaviour through both high abundances of spawning and weakened post-spawning
      cuttlefish in a small area (>10,000 animals on several kilometres of narrow rocky
      reef), as well as potential long-term and regular visitation by dolphin pods to
      this site.

PMID- 19156211
TI  - Neuroblastoma cell lines contain pluripotent tumor initiating cells that are
      susceptible to a targeted oncolytic virus.
AB  - BACKGROUND: Although disease remission can frequently be achieved for patients
      with neuroblastoma, relapse is common. The cancer stem cell theory suggests that
      rare tumorigenic cells, resistant to conventional therapy, are responsible for
      relapse. If true for neuroblastoma, improved cure rates may only be achieved via
      identification and therapeutic targeting of the neuroblastoma tumor initiating
      cell. Based on cues from normal stem cells, evidence for tumor populating
      progenitor cells has been found in a variety of cancers. METHODOLOGY/PRINCIPAL
      FINDINGS: Four of eight human neuroblastoma cell lines formed tumorspheres in
      neural stem cell media, and all contained some cells that expressed neurogenic
      stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be
      induced into multi-lineage differentiation. LA-N-5 spheres were further studied
      and showed a verapamil-sensitive side population, relative resistance to
      doxorubicin, and CD133+ cells showed increased sphere formation and
      tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic
      mutation, are emerging as next generation anticancer therapeutics. Because
      oncolytic viruses circumvent typical drug-resistance mechanisms, they may
      represent an effective therapy for chemotherapy-resistant tumor initiating cells.
      A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within
      and killed neuroblastoma tumor initiating cells preventing their ability to form
      tumors in athymic nude mice. CONCLUSIONS/SIGNIFICANCE: These results suggest that
      human neuroblastoma contains tumor initiating cells that may be effectively
      targeted by an oncolytic virus.

PMID- 19156213
TI  - The neurotensin receptor-1 pathway contributes to human ductal breast cancer
      progression.
AB  - BACKGROUND: The neurotensin (NTS) and its specific high affinity G protein
      coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate
      for one of the factors implicated in neoplastic progression. In breast cancer
      cells, functionally expressed NT1 receptor coordinates a series of transforming
      functions including cellular migration and invasion. METHODS AND RESULTS: we
      investigated the expression of NTS and NTSR1 in normal human breast tissue and in
      invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS
      is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS
      is also found expressed in the ductal and invasive components of IDCs. The high
      expression of NTSR1 is associated with the SBR grade, the size of the tumor, and
      the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is
      an independent factor of prognosis associated with the death of patients.
      CONCLUSION: these data support the activation of neurotensinergic deleterious
      pathways in breast cancer progression.

PMID- 19156214
TI  - Novel exon of mammalian ADAR2 extends open reading frame.
AB  - BACKGROUND: The post-transcriptional processing of pre-mRNAs by RNA editing
      contributes significantly to the complexity of the mammalian transcriptome. RNA
      editing by site-selective A-to-I modification also regulates protein function
      through recoding of genomically specified sequences. The adenosine deaminase
      ADAR2 is the main enzyme responsible for recoding editing and loss of ADAR2
      function in mice leads to a phenotype of epilepsy and premature death. Although A
      to-I RNA editing is known to be subject to developmental and cell-type specific
      regulation, there is little knowledge regarding the mechanisms that regulate RNA
      editing in vivo. Therefore, the characterization of ADAR expression and
      identification of alternative ADAR variants is an important prerequisite for
      understanding the mechanisms for regulation of RNA editing and the causes for
      deregulation in disease. METHODOLOGY/PRINCIPAL FINDINGS: Here we present evidence
      for a new ADAR2 splice variant that extends the open reading frame of ADAR2 by 49
      amino acids through the utilization of an exon located 18 kilobases upstream of
      the previously annotated first coding exon and driven by a candidate alternative
      promoter. Interestingly, the 49 amino acid extension harbors a sequence motif
      that is closely related to the R-domain of ADAR3 where it has been shown to
      function as a basic, single-stranded RNA binding domain. Quantitative expression
      analysis shows that expression of the novel ADAR2 splice variant is tissue
      specific being highest in the cerebellum. CONCLUSIONS/SIGNIFICANCE: The strong
      sequence conservation of the ADAR2 R-domain between human, mouse and rat ADAR2
      genes suggests a conserved function for this isoform of the RNA editing enzyme.

PMID- 19156215
TI  - Pleural tuberculosis in patients with early HIV infection is associated with
      increased TNF-alpha expression and necrosis in granulomas.
AB  - Although granulomas may be an essential host response against persistent
      antigens, they are also associated with immunopathology. We investigated whether
      HIV co-infection affects histopathological appearance and cytokine profiles of
      pleural granulomas in patients with active pleural tuberculosis (TB). Granulomas
      were investigated in pleural biopsies from HIV positive and negative TB pleuritis
      patients. Granulomas were characterised as necrotic or non-necrotic, graded
      histologically and investigated for the mRNA expression of IL-12, IFN-gamma, TNF
      alpha and IL-4 by in situ hybridisation. In all TB patients a mixed Th1/Th2
      profile was noted. Necrotic granulomas were more evident in HIV positive patients
      with a clear association between TNF-alpha and necrosis. This study demonstrates
      immune dysregulation which may include TNF-alpha-mediated immunopathology at the
      site of disease in HIV infected pleural TB patients.

PMID- 19156216
TI  - The 5-choice continuous performance test: evidence for a translational test of
      vigilance for mice.
AB  - BACKGROUND: Attentional dysfunction is related to functional disability in
      patients with neuropsychiatric disorders such as schizophrenia, bipolar disorder,
      and Alzheimer's disease. Indeed, sustained attention/vigilance is among the
      leading targets for new medications designed to improve cognition in
      schizophrenia. Although vigilance is assessed frequently using the continuous
      performance test (CPT) in humans, few tests specifically assess vigilance in
      rodents. METHODS: We describe the 5-choice CPT (5C-CPT), an elaboration of the 5
      choice serial reaction (5CSR) task that includes non-signal trials, thus
      mimicking task parameters of human CPTs that use signal and non-signal events to
      assess vigilance. The performances of C57BL/6J and DBA/2J mice were assessed in
      the 5C-CPT to determine whether this task could differentiate between strains.
      C57BL/6J mice were also trained in the 5CSR task and a simple reaction-time (RT)
      task involving only one choice (1CRT task). We hypothesized that: 1) C57BL/6J
      performance would be superior to DBA/2J mice in the 5C-CPT as measured by the
      sensitivity index measure from signal detection theory; 2) a vigilance decrement
      would be observed in both strains; and 3) RTs would increase across tasks with
      increased attentional load (1CRT task<5CSR task<5C-CPT). CONCLUSIONS: C57BL/6J
      mice exhibited superior SI levels compared to DBA/2J mice, but with no difference
      in accuracy. A vigilance decrement was observed in both strains, which was more
      pronounced in DBA/2J mice and unaffected by response bias. Finally, we observed
      increased RTs with increased attentional load, such that 1CRT task<5CSR task<5C
      CPT, consistent with human performance in simple RT, choice RT, and CPT tasks.
      Thus we have demonstrated construct validity for the 5C-CPT as a measure of
      vigilance that is analogous to human CPT studies.

PMID- 19156217
TI  - Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell
      lung cancer.
AB  - BACKGROUND: We have previously described a RAF oncogene driven transgenic mouse
      model for non small cell lung cancer (NSCLC). Here we examine whether tumor
      initiation and growth requires the stem cell self-renewal factor Bmi1. PRINCIPAL
      FINDINGS: In order to evaluate Bmi1 function in NSCLC two founder lines that
      differ in incidence and latency of tumor formation were compared. Ablation of
      Bmi1 expression in both lines had a dramatically decreased tumor growth. As the
      line with shorter latency matched the life span of Bmi1 knock out mice, these
      mice were chosen for further study. The absence of Bmi1 did not decrease the
      number of tumor initiation in these mice as only the size and not the number of
      tumors decreased. Reduction in tumor growth resulted from an increase in cell
      death and decrease in cell cycle progression that corresponded with up-regulation
      of the p16(INK4a) and p19(ARF). SIGNIFICANCE: The data identifies Bmi1 as an
      important factor for expansion but not initiation of RAF driven NSCLC.

PMID- 19156218
TI  - The impact of HIV infection and CD4 cell count on the performance of an
      interferon gamma release assay in patients with pulmonary tuberculosis.
AB  - BACKGROUND: The performance of the tuberculosis specific Interferon Gamma Release
      Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV
      endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold
      In-Tube (QFT-IT) in patients with culture confirmed pulmonary tuberculosis (PTB)
      in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell
      count on test performance. METHODOLOGY/PRINCIPAL FINDINGS: 161 patients with
      sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and
      measurement of CD4 cell count. The QFT-IT was positive in 74% (119/161; 95% CI:
      67-81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive
      (44/68) patients (81% vs. 65%, p = 0.02) and increased with CD4 cell count in HIV
      positive patients (test for trend p = 0.03). 23 patients (14%) had an
      indeterminate result and this proportion decreased with increasing CD4 cell count
      in HIV-positive patients (test for trend p = 0.03). Low CD4 cell count (<300
      cells/microl) did not account for all QFT-IT indeterminate nor all negative
      results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81
      92%) and did not differ between HIV-negative and HIV-positive patients (88 vs.
      83%, p = 0.39). CONCLUSIONS/SIGNIFICANCE: Sensitivity of the QFT-IT for
      diagnosing active PTB infection was reasonable when excluding indeterminate
      results and in HIV-negative patients. However, since the test missed more than
      10% of patients, its potential as a rule-out test for active TB disease is
      limited. Furthermore, test performance is impaired by low CD4 cell count in HIV
      positive patients and possibly by other factors as well in both HIV-positive and
      HIV-negative patients. This might limit the potential of the test in populations
      where HIV-infection is prevalent.

PMID- 19156219
TI  - Human cord blood stem cell-modulated regulatory T lymphocytes reverse the
      autoimmune-caused type 1 diabetes in nonobese diabetic (NOD) mice.
AB  - BACKGROUND: The deficit of pancreatic islet beta cells caused by autoimmune
      destruction is a crucial issue in type 1 diabetes (T1D). It is essential to
      fundamentally control the autoimmunity for treatment of T1D. Regulatory T cells
      (Tregs) play a pivotal role in maintaining self-tolerance through their
      inhibitory impact on autoreactive effector T cells. An abnormality of Tregs is
      associated with initiation of progression of T1D. METHODOLOGY/PRINCIPAL FINDINGS:
      Here, we report that treatment of established autoimmune-caused diabetes in NOD
      mice with purified autologous CD4(+)CD62L(+) Tregs co-cultured with human cord
      blood stem cells (CB-SC) can eliminate hyperglycemia, promote islet beta-cell
      regeneration to increase beta-cell mass and insulin production, and reconstitute
      islet architecture. Correspondingly, treatment with CB-SC-modulated
      CD4(+)CD62L(+) Tregs (mCD4CD62L Tregs) resulted in a marked reduction of
      insulitis, restored Th1/Th2 cytokine balance in blood, and induced apoptosis of
      infiltrated leukocytes in pancreatic islets. CONCLUSIONS/SIGNIFICANCE: These data
      demonstrate that treatment with mCD4CD62L Tregs can reverse overt diabetes,
      providing a novel strategy for the treatment of type 1 diabetes as well as other
      autoimmune diseases.

PMID- 19156220
TI  - Use of Primary Care and by Middle Aged and Older Persons with Schizophrenia.
AB  - INTRODUCTION: Comorbid medical conditions and receipt of primary medical care are
      important aspects of healthcare for older persons with schizophrenia. This study
      describes the prevalence of comorbid medical conditions and the factors
      associated with the use of primary care treatment in a group of middle-aged and
      older persons with schizophrenia. METHODS: Using baseline data from an ongoing
      study of functional skills training (N= 236), we determined the self-reported
      prevalence of 8 common medical conditions. In addition, patients who did (n= 146)
      versus those who did not (n= 90) receive primary care treatment were compared on
      demographic characteristics, psychiatric symptoms, and comorbid medical
      conditions using both univariate and multivariate analyses. RESULTS: The most
      common medical conditions were hypertension (31%), arthritis (25%), and diabetes
      (14%) and almost 60% of the patients had one or more medical conditions. More
      than 60% of the patients had received primary care treatment during the prior 3
      months. Patients who used primary care were older, more likely to have received
      mental health treatment, and more likely to have a medical condition, especially,
      diabetes. There were no differences between the groups, however, in the severity
      of psychopathologic symptoms or cognitive deficits. Multivariate logistic
      regression analysis found that older age and diabetes were associated with
      greater utilization of primary care treatment. DISCUSSION: In middle-aged and
      older patients with schizophrenia, comorbid medical conditions were common and a
      majority of the patients did receive primary care treatment in the prior 3
      months. Older patients and those with comorbid medical conditions were more
      likely to receive primary care, but there was no relationship between severity of
      psychiatric symptoms and receipt of primary care. Additional research is needed
      to determine sociodemographic and clinical factors associated with use of primary
      care utilization in groups of participants with a broader range of psychiatric
      symptom severity and supportive environments.

PMID- 19156221
TI  - Systemic administration of tolerogenic dendritic cells ameliorates murine
      inflammatory arthritis.
AB  - The expression of various cell surface molecules and the production of certain
      cytokines are important mechanisms by which dendritic cells (DC) are able to bias
      immune responses. This paper describes the effects of the inflammatory cytokine
      tumor necrosis factor (TNF)-alpha on DC phenotype and function. TNF-alpha
      treatment resulted in upregulation of MHC class II and CD86 in the absence of
      increased cell surface CD40 and CD80 or the production of IL-12. Additionally TNF
      alpha treated cells were able to bias T cell responses towards an anti
      inflammatory profile. On a note of caution this tolerogenic phenotype of the DC
      was not stable upon subsequent TLR-4 ligation as a 4 hour pulse of the TNF-alpha
      treated DC with lipopolysaccharide (LPS) resulted in the restoration of IL-12
      production and an enhancement of their T cell stimulatory capacity which resulted
      in an increased IFN-gamma production. However, TNF-alpha treated DC, when
      administered in vivo, were shown to ameliorate disease in collagen induced
      arthritis, an experimental model of inflammatory joint disease. Mice receiving
      TNF-alpha treated DC but not LPS matured DC had a delayed onset, and
      significantly reduced severity, of arthritis. Disease suppression was associated
      with reduced levels of collagen specific IgG2a and decreased inflammatory cell
      infiltration into affected joints. In summary the treatment of DC with TNF-alpha
      generates an antigen presenting cell with a phenotype that can reduce the pro
      inflammatory response and direct the immune system towards a disease modifying,
      anti-inflammatory state.

PMID- 19156222
TI  - Frequency of regulatory T cells is not affected by transient B cell depletion
      using anti-CD20 antibodies in rheumatoid arthritis.
AB  - OBJECTIVES: Transient B cell depletion with the monoclonal anti-CD20 antibody
      rituximab has shown favourable clinical responses in patients with rheumatoid
      arthritis (RA). Recently a characteristic regeneration pattern of B cell
      subpopulations has been reported. However, little is known about the impact of B
      cell depletion on peripheral T cells in particular regulatory T cells. MATERIALS
      AND METHODOLOGY: 17 patients with RA having failed anti-TNF were treated with
      rituximab. Four colour staining was performed using CD19, CD3, CD4, CD8, CD16,
      CD56, CD25, HLA-DR, HLA-G and intracellular Foxp3 at five time points spanning up
      to 12 months after rituximab. In addition, quantification of the soluble form of
      the HLA class I molecule HLA-G by ELISA has been performed. RESULTS: Peripheral B
      cell depletion lasted 6 to 9 months. The absolute number of CD3+, CD4+ and CD8+
      lymphocytes showed no significant changes up to 1 year after B-cell depletion
      compared to before therapy. Only the relative frequency for CD3 and CD4 showed a
      significant increase (p < 0.05). In particular, CD4+CD25++ and Foxp3 positive
      regulatory T cells remained constant. The percentage of HLA-G positive cells in
      the CD4+ or CD8+ population did not change significantly either. The amount of
      sHLA-G remained without significant changes. CONCLUSION: Absolute T cell counts
      showed no significant changes after rituximab compared to the time point before
      therapy.In particular, the frequency of regulatory T cells with a CD4+CD25++
      phenotype as well as positive Foxp3 expression were numerically stable.
      Additionally, HLA-G positive regulatory T cells and soluble levels of HLA-G
      showed no significant changes.

PMID- 19156223
TI  - Factor structure of the arthritis body experience scale (ABES) in a U.S.
      population of people with osteoarthritis (OA), rheumatoid arthritis (RA),
      fibromyalgia (FM) and other rheumatic conditions.
AB  - OBJECTIVE: To examine the psychometric properties of the Arthritis Body
      Experience Scale (ABES) in a US sample of people with osteoarthritis, rheumatoid
      arthritis, fibromyalgia and other rheumatic conditions. METHODS: The ABES, with
      the scoring direction modified, was phone-administered to 937 individuals who
      self-identified as having one or more arthritis conditions based on a validated,
      US, national survey assessment tool. Descriptive statistics of demographic
      variables and factor analysis of scale items were conducted. Scale dimensionality
      was assessed using principal component analysis (PCA) with oblique rotation.
      Criteria for assessing factors were eigenvalues > 1, visual assessment of scree
      plot, and structure and pattern matrices. RESULTS: The predominantly female
      (74.2%) and Caucasian (79.9%) sample had a mean age of 61.0 +/- 13.1 years, and a
      mean BMI of 30.2 +/- 7.1. Major arthritis conditions reported were rheumatoid
      arthritis, osteoarthritis and fibromyalgia. A three-factor structure with
      cronbach alpha values of .84, .85 and .53 was elicited, and accounted for 72% of
      the variance. DISCUSSION: Compared to the two-factor structure evidenced by the
      original ABES scale in a sample of UK adults, the data from this sample evidenced
      a three-factor structure with higher variance. The third factor's cronbach alpha
      of .53 was low and could be improved by the addition of salient questions derived
      from further qualitative interviews with patients with arthritis and other
      rheumatic conditions and from current literature findings. CONCLUSION: The
      observed psychometrics indicate the scale usefully assesses body image in
      populations with arthritis and related conditions. However, further testing and
      refinement is needed to determine its utility in clinical and other settings.

PMID- 19156224
TI  - Pregnancy outcome in systemic lupus erythematosus (SLE) is improving: Results
      from a case control study and literature review.
AB  - OBJECTIVES: For women who suffer from systemic lupus erythematosus (SLE),
      pregnancy can be a concern, placing the mother and fetus at risk. Our objectives
      were to assess the risk of adverse pregnancy outcome, disease flares, fertility
      rate, and co-morbidities in SLE women compared to healthy controls. We also
      systematically reviewed the literature available on pregnancy outcome in SLE to
      compare our results to other published data. Our hypothesis was that pregnancy
      outcome in SLE is improving over time. METHODS: A case-control study comparing
      self-report of the above-mentioned parameters in SLE (N=108) vs healthy controls
      or patients with non-inflammatory musculoskeletal (MSK) disorders (N=134) was
      performed. Data were collected using a self-administered questionnaire.
      Proportions, means and odds ratios were calculated. We searched and quantified
      the literature on pregnancy outcome, lupus reactivation and fertility rate. Data
      were summarized and presented in mean % +/- SEM and median % with interquartile
      range (IQR). RESULTS: Gynecological history, fertility rate and age at first
      pregnancy in SLE patients were comparable to controls. Eighteen percent of SLE
      patients reported a flare and 18% reported an improvement of symptoms during
      pregnancy. Twenty-four percent of lupus patients had at least one preterm
      delivery vs 5% in controls (OR =8.32, p = 0.0008), however other pregnancy
      outcomes (miscarriage, therapeutic abortion, stillbirth and neonatal death rate)
      did not differ between the groups. Thyroid problems were reported to be more
      likely in SLE patients (p = 0.02), but the prevalence of other co-morbidities was
      similar to controls. A literature review demonstrated that fertility was not
      affected in SLE patients. Lupus reactivations are common during pregnancy (36.5%
      +/- SEM 3.3%). Most agreed that SLE pregnancies had more fetal loss (19.5% +/-
      SEM 1.6%) and preterm births (25.5% +/- SEM 2.2%) when compared to the general
      population. Over time, the rate of SLE peripartum flares has improved (p = 0.002)
      and the proportion of pregnancies resulting in live birth has increased (p =
      0.024). The frequency of fetal death has not significantly changed. Our findings
      from the case-control study were, in general, consistent with the literature
      including the frequency of fetal death, neonatal death, live births and pregnancy
      rate. CONCLUSION: Prematurity (25.5% +/- SEM 2.2%) and fetal death (19.5% +/- SEM
      1.6%) in SLE pregnancy are still a concern. However, new strategies with respect
      to pregnancy timing and multidisciplinary care have improved maternal and fetal
      outcome in SLE.

PMID- 19156225
TI  - Altered energy homeostasis and resistance to diet-induced obesity in KRAP
      deficient mice.
AB  - Obesity and related metabolic disorders have become leading causes of adult
      morbidity and mortality. KRAP (Ki-ras-induced actin-interacting protein) is a
      cytoskeleton-associated protein and a ubiquitous protein among tissues,
      originally identified as a cancer-related molecule, however, its physiological
      roles remain unknown. Here we demonstrate that KRAP-deficient (KRAP(-/-)) mice
      show enhanced metabolic rate, decreased adiposity, improved glucose tolerance,
      hypoinsulinemia and hypoleptinemia. KRAP(-/-) mice are also protected against
      high-fat diet-induced obesity and insulin resistance despite of hyperphagia.
      Notably, glucose uptake in the brown adipose tissue (BAT) in KRAP(-/-) mice is
      enhanced in an insulin-independent manner, suggesting that BAT is involved in
      altered energy homeostasis in KRAP(-/-) mice, although UCP (Uncoupling protein)
      expressions are not altered. Of interest is the down-regulation of fatty acid
      metabolism-related molecules, including acetyl-CoA carboxylase (ACC)-1, ACC-2 and
      fatty acid synthase in the liver of KRAP(-/-) mice, which could in part account
      for the metabolic phenotype in KRAP(-/-) mice. Thus, KRAP is a novel regulator in
      whole-body energy homeostasis and may be a therapeutic target in obesity and
      related diseases.

PMID- 19156226
TI  - Perceptual other-race training reduces implicit racial bias.
AB  - BACKGROUND: Implicit racial bias denotes socio-cognitive attitudes towards other
      race groups that are exempt from conscious awareness. In parallel, other-race
      faces are more difficult to differentiate relative to own-race faces--the "Other
      Race Effect." To examine the relationship between these two biases, we trained
      Caucasian subjects to better individuate other-race faces and measured implicit
      racial bias for those faces both before and after training. METHODOLOGY/PRINCIPAL
      FINDINGS: Two groups of Caucasian subjects were exposed equally to the same
      African American faces in a training protocol run over 5 sessions. In the
      individuation condition, subjects learned to discriminate between African
      American faces. In the categorization condition, subjects learned to categorize
      faces as African American or not. For both conditions, both pre- and post
      training we measured the Other-Race Effect using old-new recognition and implicit
      racial biases using a novel implicit social measure--the "Affective Lexical
      Priming Score" (ALPS). Subjects in the individuation condition, but not in the
      categorization condition, showed improved discrimination of African American
      faces with training. Concomitantly, subjects in the individuation condition, but
      not the categorization condition, showed a reduction in their ALPS. Critically,
      for the individuation condition only, the degree to which an individual subject's
      ALPS decreased was significantly correlated with the degree of improvement that
      subject showed in their ability to differentiate African American faces.
      CONCLUSIONS/SIGNIFICANCE: Our results establish a causal link between the Other
      Race Effect and implicit racial bias. We demonstrate that training that
      ameliorates the perceptual Other-Race Effect also reduces socio-cognitive
      implicit racial bias. These findings suggest that implicit racial biases are
      multifaceted, and include malleable perceptual skills that can be modified with
      relatively little training.

PMID- 19156227
TI  - Differentiation of rabbit bone marrow mesenchymal stem cells into corneal
      epithelial cells in vivo and ex vivo.
AB  - PURPOSE: To examine whether bone marrow mesenchymal stem cells (MSCs) could be
      differentiated into corneal epithelial cells in vivo and ex vivo. METHODS: In
      vivo, BrdU labeled rabbit MSCs (Rb-MSCs) were suspended in the fibrin gels and
      transplanted onto the surface of the damaged rabbit corneas. Histology and
      molecular phenotype were studied on postoperative day 28. In vitro, labeled Rb
      MSCs were cultured for three days in two different systems: (1) Group A: Rb-MSCs
      were co-cultured with rabbit limbal stem cells (Rb-LSCs) by the Transwell culture
      system. A suspension of Rb-LSCs was added to the upper membrane surface, and the
      inserts were positioned in the culture wells, which were incubated with Rb-MSCs;
      (2) Group B: Supernatant medium that had first been used to culture Rb-LSCs and
      then filtered with a 0.45 mum filter was used to culture Rb-MSCs. For both
      groups, immunofluorescence and flow cytometric analysis were used to examine the
      expression of cytokeratin 3 (CK3) in differentiated Rb-MSCs. RESULTS: In vivo,
      the data showed that following transplantation of Rb-MSCs, the rabbit's damaged
      corneal surface was successfully reconstructed and that some Rb-MSCs participated
      in the healing of the injured corneal epithelium and expressed CK3. In vitro, the
      data showed that Rb-MSCs rapidly differentiated into cells with a morphological
      and molecular phenotype of corneal epithelial-like cells. For both groups, the
      differentiated Rb-MSCs were positive for corneal epithelial-specific marker CK3.
      In Group A, flow cytometry analysis showed that at day one, only 3.46+/-1.9% of
      cells expressed CK3. This increased to 7.24+/-3.80% at day two and decreased
      slightly (5.50+/-3.33%) at day three. The proportion of CK3 in Group B was 4.09+/
      1.84% at day one, rising to 9.31+/-5.92% after 24 h, but falling (4.37+/-2.61%)
      at day three. The mean differences are significant between each group and the
      negative control, but was not significant between Group A and Group B.
      CONCLUSIONS: MSCs could differentiate into corneal epithelial-like cells in vivo
      and ex vivo.

PMID- 19156228
TI  - Texas Heart Institute Medal and the Ray C. Fish Award for Scientific Achievement
      in Cardiovascular Diseases.

PMID- 19156229
TI  - Elephant medicine revisited.

PMID- 19156230
TI  - Matrix metalloproteinase-1 and tissue inhibitors do not predict incident coronary
      artery disease in the atherosclerosis risk in communities (ARIC) study.
AB  - Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix
      metalloproteinases (TIMPs) are thought to be associated with coronary artery
      disease. The association of these markers with incident coronary artery disease
      has not been well described. Using a case-cohort design, we selected 216
      individuals who had incident coronary artery disease (case group) and 225
      individuals from a cohort random sample (comparison group) from participants
      enrolled in the Atherosclerosis Risk in Communities study. We measured plasma
      levels of MMP-1 and TIMP-1, traditional risk factors, and other markers of
      inflammation. We found no significant difference in TIMP-1 levels between the
      case group (827.8 +/- 23.8 ng/mL) and the comparison group (819.31 +/- 16.1
      ng/mL) (P=0.77), and no significant difference in the frequency of MMP-1 levels
      that were dichotomized at the minimum detectable value of 1.7 ng/mL (P=0.49). In
      models adjusted for age, sex, race, body mass index, hypertension, diabetes,
      total cholesterol, high-density lipoprotein cholesterol, triglycerides,
      fibrinogen, von Willebrand factor, and white blood cell count, the hazard-rate
      ratio for incident coronary artery disease was 1.14 (95% confidence interval,
      0.63-2.04; P=0.67) for individuals whose TIMP-1 levels were above, versus at or
      below the mean, and 1.17 (95% confidence interval, 0.63-2.19; P=0.62) for
      individuals whose MMP-1 levels were above 1.7 ng/mL. We conclude that TIMP-1 and
      MMP-1 levels in plasma were not predictive of incident coronary artery disease in
      a case-cohort random sample of the Atherosclerosis Risk in Communities study, a
      population study of asymptomatic middle-aged adults who had no prevalent
      atherosclerosis upon enrollment.

PMID- 19156231
TI  - Carotid endarterectomy versus carotid artery stenting: findings in regard to
      neuroclinical outcomes and diffusion-weighted imaging.
AB  - The purpose of our study was to evaluate prospectively the frequency and
      significance of brain lesions after elective carotid endarterectomy (CAE) and
      carotid artery stenting (CAS) by using diffusion-weighted magnetic resonance
      imaging (DW MRI) and then to correlate imaging findings with neuroclinical
      outcomes. From February 2003 through March 2005, 95 consecutive patients
      underwent surgical endarterectomy or CAS (with a cerebral protection device) at
      our institution. A total of 59 CAE procedures were performed in 46 consecutive
      patients (mean age, 65.8 +/- 9 yr), and 56 CAS procedures were performed in 49
      consecutive patients (mean age, 66.3 +/- 9 yr). Diffusion-weighted magnetic
      resonance imaging of the brain was performed in all patients within 24 hours of
      the procedure, both before and after. The post-procedural stroke rate was
      slightly higher in the CAS group, but this difference was not significant (5.4%
      vs 0). One early and 1 late death occurred in the stent group. Although the
      incidence of ischemic lesions was similar in both groups (surgery group, 12.5%;
      stent group, 13.5%), new DW MRI lesions were higher in the endarterectomy group
      (27.1% vs 12.5%, P=0.041). This difference was due chiefly to nonischemic lesions
      such as hemorrhage and watershed ischemia. In the analysis of patients with
      embolic ischemia, incidences of symptomatic stroke (P=0.046) and large infarct
      (P=0.013) were higher in the stent group. When we used protective devices during
      CAS, the incidence of embolic complications was similar to that of surgical
      enarterectomy. On the other hand, the clinical results of CAS need improvement.

PMID- 19156232
TI  - Surgical management of spontaneous coronary artery dissection.
AB  - Spontaneous coronary artery dissection, which causes acute coronary syndrome and
      can result in sudden death, is rare; but its true incidence is underestimated,
      since most patients die suddenly, without diagnosis. The aim of this study was to
      show the importance of prompt diagnosis and treatment. In reviewing the records
      of 5,000 consecutive patients who underwent coronary angiography between January
      2001 and August 2006, we found 6 cases of spontaneous coronary artery dissection
      (an incidence rate of 0.12%). Five patients presented with left main coronary
      artery dissection and 1 patient, with right coronary artery dissection.
      Angioplasty with stenting failed in the patient with right coronary artery
      dissection. Coronary artery bypass surgery was performed in all patients. The
      patient with right coronary artery dissection died of sepsis on the 30th
      postoperative day. The other 5 patients (83.3%) are still free of symptoms, and
      they had negative results on stress tests at the 6- and 12-month follow-up visits
      after coronary artery bypass surgery. The clinical presentation of spontaneous
      left main coronary artery dissection was similar to that of atherosclerotic
      disease. However, early diagnosis of spontaneous coronary artery dissection by
      means of coronary angiography is of paramount importance, because urgent coronary
      artery bypass grafting can be lifesaving.

PMID- 19156233
TI  - Acute coronary syndrome without significant stenosis on angiography:
      characteristics and prognosis.
AB  - The characterization of patients who have acute coronary syndrome (ACS) without
      critical stenosis is unclear. First, we wanted to learn more about the
      angiographic and demographic characteristics of patients with non-ST-segment
      elevation myocardial infarction who were not in need of percutaneous coronary
      intervention (PCI) or coronary artery bypass grafting (CABG). Second, we wanted
      to look for further cardiac events during follow-up. We retrospectively analyzed
      all patients with ACS plus ischemic-marker elevation from May 2002 through
      September 2005. Follow-up was obtained primarily by telephone interviews. Of the
      1,437 ACS patients who were screened, 127 (8.8%) had noncritical stenosis (study
      group), and 509 (35.4%) had sufficient stenosis (>50%) to warrant PCI (control
      group). Patients with noncritical stenosis (< or =50%) were significantly
      younger, were more frequently women, and had fewer risk factors. Myocardial
      infarction or PCI/CABG occurred in no patients with noncritical stenosis (follow
      up, 12.2 mo) and in 5.1% or 16.1% (respectively) of patients with critical
      stenosis (follow-up, 11.1 mo; P <0.05 for revascularization). Cardiac death was
      more likely in patients without critical stenosis, but insignificantly so (2.4%
      vs 1.8%, P=0.6). SUBANALYSIS: Of patients without critical stenosis, 52.8% had
      smooth coronary arteries, and 47.3% had mild-to-moderate atherosclerosis
      (stenosis < or =50%). Follow-up revealed no deaths in the 1st subgroup and 3
      cardiac deaths (5%) in the 2nd (P=0.06). We conclude that the prognosis of
      patients without significant stenosis was significantly better in regard to
      revascularization, but statistically the same in regard to mortality.

PMID- 19156234
TI  - The cardioprotective role of preinfarction angina as shown in outcomes of
      patients after first myocardial infarction.
AB  - This prospective study evaluated the relationship between preinfarction angina (2
      months before a 1st acute myocardial infarction) and the extent of postinfarction
      myocardial injury, myocardial perfusion, contractile function, and late recovery
      of global left ventricular contractile function. We enrolled 46 patients who had
      been admitted for a 1st, single-vessel-disease, acute myocardial infarction. Low
      dose dobutamine echocardiography and technetium-99m-tetrofosmin scintigraphy were
      performed on all patients 7 to 10 days after acute myocardial infarction; and
      resting echocardiography was performed 7 to 12 months later. Twenty-seven of 46
      (58.7%) patients had experienced angina before acute myocardial infarction, and
      19 of 46 (41.3%) had not. There was no difference between the 2 groups in acute
      basal left ventricular ejection fraction (P=0.17) or in basal wall motion score
      index (P=0.521). The maximal creatine kinase-MB level was lower in the
      preinfarction-angina group (P=0.039). Patients with preinfarction angina had
      significantly more myocardial segments with preserved regional contractile
      function (P <0.0001) and significantly fewer segments with less than 50%
      perfusion (P=0.008). Stepwise regression analysis identified preinfarction angina
      (r2=0.317, P=0.032) as a significant predictor of the percentage of left
      ventricular ejection fraction recovery after the follow-up period. In our study,
      preinfarction angina was associated with decreased infarct size and with better
      protection of global and regional left ventricular contractility and improved
      preservation of the microvasculature. A history of preinfarction angina should be
      of value in predicting the late clinical outcomes of patients after a 1st acute
      myocardial infarction.

PMID- 19156235
TI  - Retractable-needle catheters: an update on local drug delivery in coronary
      interventions.
AB  - In the treatment of coronary artery disease, local delivery of pharmaceutical
      substances has long been a goal, yet the technology is still evolving. Coronary
      stents have become the predominant means of treating obstructive lesions, and the
      need for additional pharmacologic treatment is evidenced by the popularity of
      drug-eluting stents. Moreover, stents have residual limitations, in particular in
      stent thrombosis and late restenosis. Investigators have recently proposed
      delivering coronary drugs by means of local injection devices. These innovative
      devices, which incorporate retractable needles at the tip of a catheter, appear
      to be ready for clinical testing. In addition to solving many of the limitations
      of drug-eluting stents, local injection devices may eventually enable
      interventional cardiologists to treat vulnerable plaques. Herein, we review the
      evolution and current status of local drug delivery in the coronary arteries,
      with an emphasis on novel catheters that have retractable needles.

PMID- 19156236
TI  - A modification to the Manouguian aortoplasty for biological valve implantation in
      patients with small (< or =19 mm) aortic anuli--rationale and benefit.
AB  - Enlargement of a small aortic root using the Manouguian technique for biological
      valve implantation can be challenging when rigid, severely calcified noncoronary
      parts of the aortic anulus are encountered in combination with outsized heights
      of interleaflet triangles. To maximize the efficacy of the Manouguian technique,
      we applied a modification--the rationale, technical details, and benefits of
      which we describe herein.

PMID- 19156237
TI  - Does minimal-access aortic valve replacement reduce the incidence of
      postoperative atrial fibrillation?
AB  - As the most common sequela of cardiac valvular surgery, atrial fibrillation (AF)
      has an important impact on postoperative morbidity. Minimal-access aortic valve
      replacement (AVR), with purported benefits on operative outcomes, has emerged as
      an alternative to conventional AVR. We used meta-analysis to determine whether
      minimal access influences the incidence of postoperative AF after AVR. Further,
      we sought first to evaluate via sensitivity analysis the impact of any
      differences and to identify the sources of possible heterogeneity between
      studies; second, we sought to evaluate any indirect effect of minimal-access AVR
      on other surrogate outcomes related to postoperative AF. We identified 10 studies
      from 26 comparative randomized and nonrandomized reports that documented the
      primary outcome of interest: new-onset AF. Overall meta-analysis showed no
      significant difference between minimal-access and conventional AVR in the
      incidence of postoperative AF (odds ratio, 0.85; 2,262 patients; P=0.24; 95%
      confidence interval, 0.66-1.11). Nor were there any apparent differences in
      surrogate outcome measures of intensive care unit stay, total length of stay, or
      stroke among studies that displayed a notable difference in AF incidence between
      groups. Sensitivity analysis that included only high-quality studies similarly
      showed no significant difference in the incidence of AF and further showed
      several intraoperative variables as potential sources of heterogeneity between
      studies. Therefore, minimal access may not have a significant effect on
      postoperative AF. Future randomized studies must take into account the potential
      sources of heterogeneity identified here to better demonstrate any differences
      between the 2 approaches in the onset of AF.

PMID- 19156238
TI  - Treating acute "no-reflow" with intracoronary adenosine in 4 patients during
      percutaneous coronary intervention.
AB  - Angiographic evidence of impaired tissue perfusion, known as the "no-reflow"
      phenomenon, is a serious complication of percutaneous coronary intervention-one
      that is associated with increased mortality rates. Adenosine is an endogenous
      nucleoside that attenuates many of the mechanisms that are responsible for no
      reflow. Herein, we report the cases of 4 patients who developed the no-reflow
      phenomenon after elective percutaneous coronary intervention to their native
      coronary arteries and saphenous vein grafts. In all 4 patients, and without
      adverse effects, small bolus doses of adenosine through the guiding catheter
      improved epicardial perfusion--measured by either Thrombolysis In Myocardial
      Infarction (TIMI) flow grade or corrected TIMI frame count-and tissue-level
      perfusion, graded according to myocardial blush. In view of adenosine's extremely
      short half-life in blood, the continuous administration of adenosine into the
      distal vascular bed throughout percutaneous coronary intervention may further
      improve outcomes by reversing or preventing the no-reflow phenomenon.

PMID- 19156239
TI  - Clinical experience with the TandemHeart percutaneous ventricular assist device
      as a bridge to cardiac transplantation.
AB  - Cardiac support with a ventricular assist device is among the few treatments for
      heart-failure patients who have profound cardiogenic shock unresponsive to
      vasopressors and intra-aortic balloon pumps. The TandemHeart percutaneous
      ventricular assist device can provide temporary support until another device can
      be placed or a donor heart becomes available. We examined the TandemHeart's
      effect on cardiac index, central venous pressure, mixed venous oxygen saturation,
      creatinine, mean arterial pressure, urine output, and 30-day mortality rate in 5
      heart-failure patients (2 with nonischemic and 3 with ischemic cardiomyopathy;
      mean preoperative left ventricular ejection fraction, 0.17 +/- 0.056). Two
      patients were undergoing cardiopulmonary resuscitation when the device was
      inserted. The average duration of TandemHeart support was 7.6 +/- 3.2 days; all
      patients were successfully bridged to transplantation. The TandemHeart improved
      the cardiac index (1.9 +/- 0.3 vs 3.5 +/- 0.8 L/[min.m2], P= 0.01), mean arterial
      pressure (69 +/- 12.5 vs 91 +/- 4.3 mmHg, P=0.009), mixed venous oxygen
      saturation (45.4 +/- 14.3 vs 71.4 +/- 7.5, P=0.009), and urine output (1,861 +/-
      988 vs 4,314 +/- 1,346 mL/hr, P=0.01). The device decreased central venous
      pressure (21.2 +/- 7.4 vs 12.8 +/- 5.9 mmHg, P=0.02) and pressor requirements
      (2.4 +/- 1.1 vs 1.0 +/- 0.7 agents, P=0.02). Average long-term follow-up after
      heart transplantation was 8.4 +/- 9.9 months, with no deaths. We conclude that
      the TandemHeart can provide hemodynamic support for patients with profound,
      refractory cardiogenic shock. Furthermore, the device can bridge patients to
      cardiac transplantation and can be placed percutaneously, without invasive
      surgery.

PMID- 19156240
TI  - Repair of total anomalous pulmonary venous return: results after 47 years.
AB  - We present herein the case of a 48-year-old patient who had undergone repair of
      total anomalous pulmonary venous return at the age of 14 months, in March 1960,
      at Texas Children's Hospital. When this patient voluntarily underwent re
      examination in 2007, echocardiography revealed the late results of surgery that
      had been performed 47 years earlier: normal pulmonary venous velocity, patent
      pulmonary venous return, and no substantial electrocardiographic abnormalities.
      This patient is perhaps the oldest known survivor of surgical repair of total
      anomalous pulmonary venous return.

PMID- 19156241
TI  - Right atrial thrombus mimicking myxoma with pulmonary embolism in a patient with
      systemic lupus erythematosus and secondary antiphospholipid syndrome.
AB  - Antiphospholipid syndrome is a well-defined entity that is characterized by
      spontaneous abortion, thrombocytopenia, and recurrent arterial and venous
      thromboses. A partially calcified right atrial thrombus mimicking myxoma with
      recurrent pulmonary embolism has not been previously reported in a patient who
      also had systemic lupus erythematosus and secondary antiphospholipid syndrome.
      Herein, we describe the case of a 37-year-old woman with systemic lupus
      erythematosus and secondary antiphospholipid syndrome who was admitted to the
      hospital with progressive exertional dyspnea. Ventilation-perfusion scanning
      showed multiple parenchymal defects in the lungs that portended pulmonary
      embolism. In addition, the scanning revealed normal regional ventilation.
      Transthoracic and transesophageal echocardiography showed a right atrial mass
      that was highly suggestive of myxoma, and the patient subsequently underwent
      surgery. A histologic examination showed an organized, partially calcified
      thrombus. Intracardiac thrombus has been rarely reported as a complication of
      antiphospholipid syndrome. In our patient, the preoperative investigations could
      not differentiate the partially calcified right atrial thrombus from a myxoma,
      and the diagnosis was made postoperatively.

PMID- 19156242
TI  - Intrapericardial primary thymic carcinoma in a 73-year-old man.
AB  - Thymic carcinoma is a rare, highly aggressive type of tumor that typically occurs
      in the anterior mediastinum. We describe the case of a 73-year-old man who
      presented with weakness, cough, dyspnea, anorexia, and weight loss. An
      echocardiogram showed an intrapericardial mass that occupied the space around the
      lateral walls of the left ventricle and distally compressed the right ventricle.
      Magnetic resonance imaging and a biopsy confirmed the presence of
      intrapericardial primary thymic carcinoma. The patient underwent surgical
      excision of the tumor and died of right ventricular rupture during the procedure.
      This case highlights the importance of considering thymic carcinoma whenever an
      otherwise unexplained intrapericardial mass is encountered.

PMID- 19156243
TI  - TandemHeart insertion via a femoral arterial GORE-TEX graft conduit in a high
      risk patient.
AB  - The TandemHeart percutaneous ventricular assist device (pVAD), which provides
      temporary circulatory support of the left ventricle, can be used in high-risk and
      hemodynamically unstable patients. The easily inserted TandemHeart provides
      cardiac support superior to that from the use of intra-aortic balloon pumps.
      Herein, we discuss TandemHeart implantation via end-to-side femoral arterial
      grafting in a cardiac patient whose sepsis and multiorgan failure were
      complicated by coagulopathy and thromboembolism. A 47-year-old woman, on intra
      aortic balloon and intravenous inotropic support after an acute myocardial
      infarction and emergency coronary artery bypass grafting, was transferred to our
      institution via helicopter. She developed sepsis and multiorgan failure. Her
      condition was further complicated by coagulopathy and a left-lower-extremity
      thromboembolism. After 6 weeks of aggressive pharmacologic and intermittent intra
      aortic balloon treatment, the patient developed cardiogenic shock and received a
      TandemHeart pVAD for short-term circulatory support. A GORE-TEX access graft,
      sewn end-to-side to the femoral artery because of the patient's leg ischemia and
      very small vessels, served as a conduit for the TandemHeart's femoral arterial
      inflow cannula. Her difficult circulatory, anatomic, and coagulopathic status
      stabilized after 2 weeks of TandemHeart support, and she was bridged to the long
      term MicroMed DeBakey VAD Child in anticipation of heart transplantation. The
      case of our patient shows that high-risk patients who have experienced
      cardiogenic shock with multiorgan failure and coagulopathy can benefit from the
      TandemHeart pVAD as a bridge to other therapeutic options, even when creative
      approaches to treatment and to TandemHeart insertion are required.

PMID- 19156244
TI  - Repair of coarctation-related aortic arch aneurysm and ventricular septal defect
      in an adolescent.
AB  - A saccular aortic arch aneurysm that is secondary to aortic arch coarctation and
      that is accompanied by a ventricular septal defect is a rare combination in the
      adolescent patient. Total simultaneous repair of all of these conditions is
      desirable, because of the higher morbidity and mortality rates of staged
      procedures-particularly when resection of the saccular aneurysm is delayed.
      Herein, we discuss the case of a 16-year-old boy who underwent simultaneous
      surgical correction of these malformations. With the aid of cardiopulmonary
      bypass on the beating heart, the coarctation and the aneurysmal segment were
      resected, and a tubular Dacron graft was interposed. The ascending aorta and
      femoral artery were both then cannulated to ensure whole-body perfusion during
      cardiopulmonary bypass. The ventricular septal defect was closed with the patient
      under cardioplegic arrest. After 10 days, he was discharged from the hospital
      without sequelae. We conclude that single-staged repair of cardiac abnormalities
      and of an aortic arch aneurysm that is secondary to coarctation of the aortic
      arch can be performed safely and effectively in adolescent and adult patients by
      use of our technique.

PMID- 19156245
TI  - Coronary artery bypass grafting after pneumonectomy.
AB  - When open-heart operations are necessary in patients who have undergone
      pneumonectomy, the unavoidable shift of mediastinal structures should be
      carefully considered. Surgical access, revascularization procedures, and the
      institution of cardiopulmonary bypass can all require approaches that differ from
      the usual. In particular, no general recommendations exist regarding the
      management of patients who undergo coronary artery bypass grafting after
      pneumonectomy. We successfully performed coronary artery bypass grafting in a 57
      year-old man who had undergone a left pneumonectomy 7 years previously. Because
      the patient's heart was completely displaced into the left posterior hemithorax,
      access via a left posterolateral thoracotomy was chosen. Saphenous vein grafts
      were chosen over the internal mammary artery. The distal anastomoses were
      performed with use of the off-pump technique; for the proximal anastomosis, 2
      venous grafts were implanted into the descending aorta. The patient's
      postoperative course was uneventful, and postoperative angiography revealed
      patent grafts. Herein, we discuss the case of this patient, and we present some
      considerations that can influence surgical approaches in similar circumstances.

PMID- 19156246
TI  - Simultaneous coronary and cerebral air embolism after CT-guided core needle
      biopsy of the lung.
AB  - An air embolism in the arterial system is a rare but serious sequela of lung
      biopsy. We describe the case of a patient who presented with acute cardiac and
      cerebral air embolism, including simultaneous acute ST-segment elevation
      myocardial infarction, atrial fibrillation, unresponsiveness, seizure, and
      stroke. Computed tomographic imaging revealed air pockets in the right coronary
      artery and aorta. The patient made a full recovery after aggressive medical
      treatment and hyperbaric oxygen therapy.

PMID- 19156247
TI  - Thrombus straddling an atrial septal defect: surgical prevention of massive
      pulmonary and systemic embolization.
AB  - A large thrombus entrapped in an atrial septal defect is a rare condition that
      can lead to life-threatening systemic and pulmonary embolization. The use of
      thrombolysis may prove dangerous to the patient. Herein, we describe the
      emergency surgical management that contributed to a successful outcome in a 67
      year-old man who was found to have a 23-cm-long thrombus across an atrial septal
      defect.

PMID- 19156248
TI  - Split right coronary artery: its definition and its territory.
AB  - We report here, for perhaps the 1st time in the English-language literature, the
      extent of the territory fed by the anterior bifurcation of the (anomalous) split
      right coronary artery (RCA). A 64-year-old man presented with an occlusion of the
      anterior bifurcation of a split RCA--which resulted in an infarct that involved
      both the inferoseptal left ventricular wall and the anterior right ventricular
      free wall. Split RCA is the same anomaly as the improperly named "double right
      coronary artery." In reality, there are not 2 RCAs, but only split portions of
      the posterior descending branch of the RCA, with 2 separate proximal courses.

PMID- 19156249
TI  - Transient left ventricular apical ballooning complicated by a mural thrombus and
      outflow tract obstruction in a patient with pheochromocytoma.

PMID- 19156250
TI  - Transient apical ballooning in hypertrophic obstructive cardiomyopathy.

PMID- 19156251
TI  - Multislice computed tomography of a repaired anomalous left coronary artery
      arising from the pulmonary artery.

PMID- 19156252
TI  - Pacemaker endocarditis viewed via intracardiac ultrasonography.

PMID- 19156253
TI  - Cryoplasty for the treatment of in-stent renal artery stenosis?

PMID- 19156255
TI  - Shedding light on the efficacy of laboratory evolution based on iterative
      saturation mutagenesis.
AB  - Directed evolution has emerged as a general way to engineer essentially any
      catalytic property of enzymes, but due to the bottleneck imposed by the necessity
      to screen large libraries of mutants, it is often time-consuming. In order to
      make this type of protein engineering faster and more efficient than in the past,
      improved methods for probing protein sequence space need to be developed. This
      review focuses on recent advances which help to solve the traditional numbers
      problem in laboratory evolution, as in the directed evolution of enantioselective
      enzymes. Our contribution in this endeavour is iterative saturation mutagenesis
      (ISM), which can be used to enhance the enantioselectivity and/or the
      thermostability of enzymes. The option to use reduced amino acid alphabets as
      defined by the appropriate codon degeneracies supplements in a crucial way the
      toolbox in this knowledge-guided approach to laboratory evolution.

PMID- 19156257
TI  - Predicting protein evolution in vitro by phage escape technology.
AB  - The relationship between host and pathogen is inherently dynamic at the genetic
      level. A plethora of host defensive systems have evolved to counteract and/or
      eliminate invading pathogens. These strategies exert selection pressure upon the
      pathogen, leading to the emergence of mechanisms to combat the host including
      immune evasion and resistance. Consequently, effective control of rapidly
      evolving diseases is contingent on the ability to predict pathogen evolution
      prior to the emergence of resistant phenotypes. Highlighted in this article is a
      bacteriophage-based technology capable of screening hundreds of millions of
      binding events simultaneously at single molecule resolution, thus providing an in
      vitro mimetic of protein evolution. This technology, termed phage escape, can be
      utilized to model the evolution of proteins in the presence of antibodies or
      other selective pressure, providing a predictive solution to the coevolution of
      antigens and the immune system. Foresight into the evolutionary path of an
      antigen and subsequent neutralization strategies can facilitate more efficacious
      vaccination formulation and have important implications in the treatment of a
      range of evolving diseases, including viral infections and cancer.

PMID- 19156256
TI  - Assessment of the CFTR and ENaC association.
AB  - Cystic fibrosis (CF) is one of the most common lethal genetic disorders. It
      results primarily from mutations in the cystic fibrosis transmembrane conductance
      regulator (cftr) gene. These mutations cause inadequate functioning of CFTR,
      which in turn leads to the severe disruption of transport function in several
      epithelia across various organs. Affected organs include the sweat glands, the
      intestine, and the reproductive system, with the most devastating consequences
      due to the effects of the disease on airways. Despite aggressive treatment,
      gradual lung failure is the major life limiting factor in patients with CF.
      Understanding of the exact manner by which defects in the CFTR lead to lung
      failure is thus critical. In the CF airway, decreased chloride secretion and
      increased salt absorption is observed. The decreased chloride secretion appears
      to be a direct consequence of defective CFTR; however, the increased salt
      absorption is believed to result from the failure of CFTR to restrict salt
      absorption through a sodium channel named the epithelial Na(+) channel, ENaC. The
      mechanism by which CFTR modulates the function of ENaC proteins is still obscure
      and somewhat controversial. In this short review we will focus on recent findings
      of a possible direct CFTR and ENaC association.

PMID- 19156259
TI  - MAR elements regulate the probability of epigenetic switching between active and
      inactive gene expression.
AB  - Gene expression often cycles between active and inactive states in eukaryotes,
      yielding variable or noisy gene expression in the short-term, while slow
      epigenetic changes may lead to silencing or variegated expression. Understanding
      how cells control these effects will be of paramount importance to construct
      biological systems with predictable behaviours. Here we find that a human matrix
      attachment region (MAR) genetic element controls the stability and heritability
      of gene expression in cell populations. Mathematical modeling indicated that the
      MAR controls the probability of long-term transitions between active and inactive
      expression, thus reducing silencing effects and increasing the reactivation of
      silent genes. Single-cell short-terms assays revealed persistent expression and
      reduced expression noise in MAR-driven genes, while stochastic burst of
      expression occurred without this genetic element. The MAR thus confers a more
      deterministic behavior to an otherwise stochastic process, providing a means
      towards more reliable expression of engineered genetic systems.

PMID- 19156258
TI  - Metallo-complex activation of neuroprotective signalling pathways as a
      therapeutic treatment for Alzheimer's disease.
AB  - Alzheimer's disease is the most common neurodegenerative disease of the elderly
      and although some drugs may delay cognitive impairment, an effective treatment
      has not yet been found. Extracellular deposition of amyloid-beta (Abeta) plaques,
      intracellular hyperphosphorylation of the microtubule associated protein, tau and
      elevated oxidative stress have long been a focus for neurotherapeutic strategies.
      More recently biometal interactions with Abeta have become a feasible target as
      they appear to play a significant role in the pathogenesis of this devastating
      disease. Metal ligands such as 8-hydroxyquinoline derivatives have been developed
      that alter these interactions and promote clearance of amyloid deposits. A novel
      neurotherapeutic approach may involve activation of neuronal cell signalling
      mechanisms using metallo-complexes. Copper or zinc complexes can activate
      phosphoinositol-3-kinase leading to downstream modulation of glycogen synthase
      kinase-3 and extracellular signal regulated kinase and this results in decreased
      tau and Abeta levels. These approaches may offer a new strategy for treating AD.
      Further in vivo investigation is required to elucidate the mechanism of action of
      these metallo-complexes in vivo and determine their efficacy and safety as
      potential treatments of neurodegenerative diseases.

PMID- 19156260
TI  - The use of Cyan Fluorescent Protein variants with a distinctive lifetime
      signature.
AB  - The use of Cyan Fluorescent Proteins, with a distinctive lifetime signature,
      opens up new alternatives to track and semi-quantify the relative expression of
      proteins in vivo using a single excitation source and emission channel.

PMID- 19156261
TI  - Transcript stability in the protein interaction network of Escherichia coli.
AB  - Gene expression is a dynamic process which can be controlled by a number of
      mechanisms as genetic information flows from nucleic acids to proteins. The study
      of gene expression in the steady state, while informative, overlooks the
      underlying dynamics of the processes. Steady-state transcript levels are a result
      of both RNA synthesis and degradation, and as such, measurements of degradation
      rates can be used to determine their rates of synthesis as well as reveal
      regulation that occurs via changes in RNA stability. Messenger RNA degradation
      plays a central role in diverse cellular processes and is controlled primarily by
      the activity of the degradosome in prokaryotes. In this study, we use the
      currently available network of protein-protein interactions (PPIs) and mRNA half
      lives in Escherichia coli to demonstrate that centrality of a protein in the PPI
      network is strongly correlated with its mRNA half-life. We find that interacting
      proteins tend to show similar half-lives, commonly referred to as assortative
      behavior in networks, which is frequently found in biological and social
      networks. While a major fraction of the interacting proteins show significantly
      lower differences in mRNA stabilities, a smaller but significant number of
      protein pairs tend to show higher differences than expected by chance. Higher
      differences in transcript stabilities often involved those that encode for
      transcription factors and enzymes, suggesting a feedback link at the post
      translational level. We also note that although essential genes, which act as a
      proxy for in vivo centrality in PPI networks, are highly expressed compared to
      non-essential ones, they do not encode for more stable transcripts than non
      essential genes. Our results provide a direct link between mRNA stability and
      centrality of a protein in PPI network indicating the importance of post
      transcriptional mechanisms on nascent RNAs in the cell.

PMID- 19156262
TI  - Human cyt P450 mediated metabolic toxicity of 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone (NNK) evaluated using electrochemiluminescent arrays.
AB  - Electrochemiluminescent (ECL) arrays containing polymer
      ([Ru(bpy)(2)(PVP)(10)](2+), PVP = polyvinylpyridine), DNA, and selected enzymes
      were employed to elucidate cytochrome (cyt) P450 dependent metabolism of the
      tobacco specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK). Bioactivated NNK metabolites formed upon H(2)O(2)-enzymatic activation
      were captured as DNA adducts and detected simultaneously from 36 spot arrays by
      capturing and quantifying emitted ECL with an overhead CCD camera. Increased ECL
      emission was dependent on NNK exposure time. Of the enzymes tested, the activity
      toward NNK bioactivation was cyt P450 1A2 > 2E1 > 1B1 approximately
      chloroperoxidase (CPO) > myoglobin (Mb) in accordance with reported in vivo
      studies. Cyt P450/polyion films were also immobilized on 500 nm diameter silica
      nanospheres for product analysis by LC-MS. Analysis of the nanosphere film
      reaction media provided ECL array validation and quantitation of the bioactivated
      NNK hydrolysis product 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) confirming
      production of reactive metabolites in the films. Chemical screening in this
      fashion allows rapid clarification of enzymes responsible for genotoxic
      activation as well as offering insight into cyt P450-related toxicity and
      mechanisms.

PMID- 19156263
TI  - A comparative evolutionary study of transcription networks. The global role of
      feedback and hierachical structures.
AB  - We present a comparative analysis of large-scale topological and evolutionary
      properties of transcription networks in three species: the two distant bacteria
      E. coli and B. subtilis, and the yeast S. cerevisiae. The study focuses on the
      global aspects of feedback and hierarchy in transcriptional regulatory pathways.
      While confirming that gene duplication has a significant impact on the shaping of
      all the analyzed transcription networks, our results point to distinct trends
      between the bacteria, which display a hierarchical network structure with short
      transcription cascades, and yeast, which seems able to sustain a higher wiring
      complexity, including larger feedback, longer transcription cascades, and the
      combinatorial use of heterodimers made of duplicate transcription factors, absent
      in E. coli.

PMID- 19156264
TI  - Identification of metabolites in human hepatic bile using 800 MHz 1H NMR
      spectroscopy, HPLC-NMR/MS and UPLC-MS.
AB  - The first application of high field NMR spectroscopy (800 MHz for (1)H
      observation) to human hepatic bile (as opposed to gall bladder bile) is reported.
      The bile sample used for detailed investigation was from a donor liver with mild
      fat infiltration, collected during organ retrieval prior to transplantation. In
      addition, to focus on the detection of bile acids in particular, a bile extract
      was analysed by 800 MHz (1)H NMR spectroscopy, HPLC-NMR/MS and UPLC-MS. In the
      whole bile sample, 40 compounds have been assigned with the aid of two
      dimensional (1)H-(1)H TOCSY and (1)H-(13)C HSQC spectra. These include
      phosphatidylcholine, 14 amino acids, 10 organic acids, 4 carbohydrates and
      polyols (glucose, glucuronate, glycerol and myo-inositol), choline,
      phosphocholine, betaine, trimethylamine-N-oxide and other small molecules. An
      initial NMR-based assessment of the concentration range of some key metabolites
      has been made. Some observed chemical shifts differ from expected database
      values, probably due to a difference in bulk diamagnetic susceptibility. The NMR
      spectra of the whole extract gave identification of the major bile acids (cholic,
      deoxycholic and chenodeoxycholic), but the glycine and taurine conjugates of a
      given bile acid could not be distinguished. However, this was achieved by HPLC
      NMR/MS, which enabled the separation and identification of ten conjugated bile
      acids with relative abundances varying from approximately 0.1% (taurolithocholic
      acid) to 34.0% (glycocholic acid), of which, only the five most abundant acids
      could be detected by NMR, including the isomers glycodeoxycholic acid and
      glycochenodeoxycholic acid, which are difficult to distinguish by conventional LC
      MS analysis. In a separate experiment, the use of UPLC-MS allowed the detection
      and identification of 13 bile acids. This work has shown the complementary
      potential of NMR spectroscopy, MS and hyphenated NMR/MS for elucidating the
      complex metabolic profile of human hepatic bile. This will be useful baseline
      information in ongoing studies of liver excretory function and organ
      transplantation.

PMID- 19156265
TI  - Transition metal catalysed reactions of alcohols using borrowing hydrogen
      methodology.
AB  - The reactivity of alcohols can be enhanced by the temporary removal of hydrogen
      using a transition metal catalyst to generate an intermediate aldehyde or ketone.
      The so-formed carbonyl compound has a greater reactivity towards nucleophilic
      addition accommodating the in situ formation of imines or alkenes. The return of
      hydrogen from the catalyst leads to the formation of new C-N and C-C bonds, often
      with water as the only reaction by-product.

PMID- 19156266
TI  - A new luminescent 3D metal-organic framework possessing a rare (3,5)-connected
      net which can be transformed from a 2D double layer.
AB  - Applying a nonplanar dicarboxylate ligand, a new 3D metal-organic framework,
      Zn(TBDC(1))(1/2)(TBDC(2))(1/2) (), possessing a rare (3,5)-connected net has been
      synthesized and characterized; complex can be formed from a 2D double layer by
      thermally liberating the coordinated water and dmf molecules, simultaneous with
      luminescence-increased changes.

PMID- 19156267
TI  - Half-sandwich chromium(III) complexes bearing beta-ketoiminato and beta
      diketiminate ligands as catalysts for ethylene polymerization.
AB  - Half-sandwich chromium(iii) complexes bearing beta-ketoiminato and beta
      diketiminate ligands were synthesized and employed as catalysts for ethylene
      polymerization in the presence of triethylaluminium.

PMID- 19156268
TI  - Direct synthesis of a new class of N,N,N ligands based on 1,2-dihydro-1,10
      phenanthroline backbone and their coordination to Pd complexes.
AB  - Reactions of acetylpyridine derivatives with 8-aminoquinolines provide a general
      and simple access to an unexpected class of versatile N,N,N ligands, which offer
      interesting perspectives in coordination chemistry.

PMID- 19156269
TI  - [(OtBu)(2)C(6)H(3)](3)Ge(+) a free germyl cation with aryl ligands.
AB  - The reaction of Ar(3)GeBr (Ar = 2,6-(OtBu)(2)C(6)H(3)), which is the side product
      of the synthesis of the metalloid germanium cluster compound Ge(8)Ar(6), with the
      silver salt of the weakly coordinating anion (WCA) [Al(OR(f))(4)](-) (R(f) =
      C(CF(3))(3)) gives the free germyl cation Ar(3)Ge(+). Quantum chemical
      calculations open an insight into the bonding situation of this first free cation
      exhibiting aryl ligands and a first reaction leading to Ar(3)GeOH is presented.

PMID- 19156271
TI  - 2,2':6',2''-Terpyridine meets 2,6-bis(1H-1,2,3-triazol-4-yl)pyridine: tuning the
      electro-optical properties of ruthenium(II) complexes.
AB  - The synthesis of a series of heteroleptic ruthenium(ii)-complexes containing
      both, 2,2':6',2''-terpyridine and 2,6-bis(1H-1,2,3-triazol-4-yl)pyridine, is
      reported for the first time. The provided complexes feature photophysical and
      electrochemical properties in between those known for the respective homoleptic
      complexes. The flexibility with respect to lateral functional groups to be
      introduced into the complexes underlines the high potential for further
      functionalization steps.

PMID- 19156272
TI  - Ionothermal synthesis of two novel metal organophosphonates.
AB  - Two novel metal phosphonates, Al(5)F(C(4)H(9)PO(3))(6)(OH)(2)(C(4)N(2)H(6))(2)
      and Ga(4)F(2)(C(4)H(9)PO(3))(8)H(5).(C(7)N(2)H(11)) have been prepared using an
      ionothermal approach and their structures solved using single-crystal X-ray
      diffraction. In , the breakdown of the ionic liquid solvent has occurred and a
      fragment of the cation coordinates to the aluminium in the structure. In , the
      ionic liquid cation acts as the template and is occluded. Compound is a chain
      structure while compound is molecular, unlike the vast majority of hydrothermally
      synthesised phosphonates, which are layered.

PMID- 19156270
TI  - Neutral and reduced Roussin's red salt ester [Fe(2)(mu-RS)(2)(NO)(4)] (R = n-Pr,
      t-Bu, 6-methyl-2-pyridyl and 4,6-dimethyl-2-pyrimidyl): synthesis, X-ray crystal
      structures, spectroscopic, electrochemical and density functional theoretical
      investigations.
AB  - A series of Roussin's red salt esters [Fe(2)(micro-RS)(2)(NO)(4)] (R = n-Pr (), t
      Bu (), 6-methyl-2-pyridyl () and 4,6-dimethyl-2-pyrimidyl ()) were synthesized by
      the reaction of Fe(NO)(2)(CO)(2) with thiols or thiolates. Complexes were
      characterized by IR, UV-vis, (1)H-NMR, electrochemistry, and single-crystal X-ray
      diffraction analysis. The IR spectra of complexes display one weak and two strong
      NO stretching frequencies (nu(NO)) in solution, but only two strong nu(NO) in the
      solid. Density functional theoretical (DFT) calculations using complex as model
      suggest that two spatial isomers of these complexes bear a 3 kcal energy
      difference in solution. Frequency calculations of the two isomers provide insight
      on the origin of the vibrational bands and explain the IR observation of
      complexes in the solid state and in solution. Cyclic voltammetry shows two quasi
      reversible, one-electron reductions for complexes and one quasi-reversible, one
      electron reduction for complexes . The paramagnetic complexes [Fe(2)(micro
      RS)(2)(NO)(4)](-) ((-)-(-)), which are prepared by the chemical reduction of
      neutral complexes [Fe(2)(micro-RS)(2)(NO)(4)] (), have also been investigated by
      EPR spectroscopy. Interestingly, the EPR spectra of complexes [Fe(2)(micro
      RS)(2)(NO)(4)](-) ((-)-(-)) exhibit an isotropic signal of g = 1.998-2.004
      without hyperfine splitting in the temperature range 180-298 K. The observations
      are consistent with the results of the calculations, which reveal that the
      unpaired electron is dominantly delocalized over the two sulfur and two iron
      atoms. The difference of the g values between the reduced form of Roussin's red
      ester and the typical dinitrosyl iron complexes is explained, for the first time,
      by the difference in unpaired electron distributions between the two types of
      complexes, which provides the theoretical bases for the use of g values as a
      spectroscopic tool to differentiate these biologically active complexes.

PMID- 19156273
TI  - MRI relaxation properties of water-soluble apoferritin-encapsulated gadolinium
      oxide-hydroxide nanoparticles.
AB  - We have prepared water-soluble gadolinium oxide nanoparticles that show potential
      as MRI contrast agents. The particles were built into the apoferritin cavity and
      have an average size of 5 nm. After seven days a loss of 5% of Gd was detected
      compared with the as-prepared samples; after that the Gd remained constant and
      stabilized inside the apoferritin, indicating that the apoferritin capsid acts as
      a Gd store, avoiding metal delivery and consequent toxicity. The NMR longitudinal
      and transverse relaxivities resulted about 10 and 70 times higher than the ones
      of clinically approved paramagnetic Gd-chelates, thus indicating the possible
      route for synthesizing a novel class of MRI contrast agents.

PMID- 19156274
TI  - Sandwich-type Hf(IV) and Zr(IV)complexes composed of tri-lacunary Keggin
      polyoxometalates: structure of [M(3)(mu-OH)(3)(A-alpha-PW(9)O(34))(2)](9-) (M =
      Hf and Zr).
AB  - The syntheses and structures of hafnium(iv) and zirconium(iv) complexes with
      Keggin tri-lacunary polyoxometalates (POM) [A-alpha-PW(9)O(34)](9-), i.e.,
      (Et(2)NH(2))(7)H(2)[Hf(3)(micro-OH)(3)(A-alpha-PW(9)O(34))(2)].11H(2)O
      (Et(2)NH(2)-) and (Et(2)NH(2))(7)H(2)[Zr(3)(micro-OH)(3)(A-alpha
      PW(9)O(34))(2)].12H(2)O (Et(2)NH(2)-) are described. The two POMs, Et(2)NH(2)-
      and Et(2)NH(2)-, were obtained as analytically pure, colorless crystals in 30.0
      and 40.9% yields, respectively, by 1:3-molar ratio reactions of [A-PW(9)O(34)](9
      ) with Hf(SO(4))(2) and Zr(SO(4))(2), respectively, in aqueous solutions at 80-90
      degrees C, followed by refluxing. The two POMs were characterized by elemental
      analysis, TG/DTA, FTIR, solution ((31)P and (183)W) NMR and X-ray
      crystallography. X-Ray structure analysis of Et(2)NH(2)- revealed that in
      polyoxoanion , the three 6-coordinate prismatic Hf(IV) ions linked with the three
      bridging OH groups, i.e., the [Hf(3)(micro-OH)(3)](9+) cluster cation was
      sandwiched between two alpha-Keggin tri-lacunary POMs. The molecular structure of
      was isostructural with that of polyoxoanion in Et(2)NH(2)-. X-Ray crystallography
      also showed that the crude crystals of Et(2)NH(2)- and Et(2)NH(2)-, which were
      first formed without refluxing, contained the two isomeric crystalline species in
      a 7:3 ratio with the alpha,alpha- and alpha,beta-junctions of the two Keggin tri
      lacunary POMs. These facts were also confirmed by (31)P NMR in D(2)O. By
      refluxing the solutions containing the crude crystals, only the alpha,alpha
      isomers of Et(2)NH(2)- and Et(2)NH(2)- were finally isolated.

PMID- 19156275
TI  - Synthesis and characterization of Co and Ni complexes stabilized by keto- and
      acetamide-derived P,O-type phosphine ligands.
AB  - The coordination properties of the beta-keto phosphine ligands R(2)PCH(2)C(O)Ph
      (, R = i-Pr; , R = Ph), of the new acetamide-derived phosphine ligand (i
      Pr)(2)PNHC(O)Me () and of Ph(2)PNHC(O)Me () have been examined towards Ni(ii)
      complexes. Comparisons are made between systems in which the PCH(2) function of
      the ketophosphine has been replaced with an isoelectronic PNH group in amide
      derived ligands, or the PCH functionality of phosphinoenolates with a PN group in
      phosphinoiminolate complexes. Furthermore, ligands and reacted with [(eta(5)
      C(5)H(5))CoI(2)(CO)] to afford the phosphine mono-adducts [(eta(5)
      C(5)H(5))CoI(2){Ph(2)PCH(2)C(O)Ph}] () and [(eta(5)
      C(5)H(5))CoI(2){Ph(2)PNHC(O)Me}] (), respectively, which upon reaction with
      excess NEt(3) yielded the phosphinoenolate complex [(eta(5)-C(5)H(5))[upper bond
      1 start]CoI{Ph(2)PCH[horiz bar, triple dot above]C([horiz bar, triple dot
      above]O[upper bond 1 end])Ph}] () and the phosphinoiminolate complex [(eta(5)
      C(5)H(5))[upper bond 1 start]CoI{Ph(2)PN[horiz bar, triple dot above]C([horiz
      bar, triple dot above]O[upper bond 1 end])Me}] (), respectively. The complexes
      cis-[[upper bond 1 start]Ni{(i-Pr)(2)PN[horiz bar, triple dot above]C([horiz bar,
      triple dot above]O[upper bond 1 end])Me}(2)] () and cis-[[upper bond 1
      start]Ni{Ph(2)PN[horiz bar, triple dot above]C([horiz bar, triple dot
      above]O[upper bond 1 end])Me}(2)] () were obtained similarly from NiCl(2) and (3)
      and (4), respectively, in the presence of a base. The phosphinoenolate complex
      [[upper bond 1 start]Ni{(i-Pr)(2)PCH[horiz bar, triple dot above]C([horiz bar,
      triple dot above]O[upper bond 1 end])Ph}(2)] () exists in ethanol as a mixture of
      the cis and trans isomers, in contrast to cis-[[upper bond 1
      start]Ni{(Ph(2)PCH[horiz bar, triple dot above]C([horiz bar, triple dot
      above]O[upper bond 1 end])Ph}(2)], and the solid-state structure of the trans
      isomer of was established by X-ray diffraction. The structures of the ligand (3)
      and of the complexes , in .3/2CH(2)Cl(2), , and have also been determined by X
      ray diffraction and are compared with those of related complexes. Complexes , and
      contain a five-membered heteroatomic metallocyclic moiety, which is constituted
      by five different chemical elements. The structural consequences of the steric
      bulk of the P substituents and of the electronic characteristics of the P,O
      chelates are discussed.

PMID- 19156276
TI  - Donor-pi-acceptor structure between Ag nanoparticles and azobenzene chromophore
      and its enhanced third-order optical non-linearity.
AB  - An amorphous silica hybrid film containing covalently linked azobenzene
      chromophores and Ag nanoparticles was synthesized by a one-step sol-gel route in
      the presence of amino trialkoxysilane (APTES). The electron transfer from the N
      containing groups in the APTES and azobenzene molecules, which are chemisorbed
      onto the surface of Ag nanoaprticles, makes the Ag nanoparticles negatively
      charged. Subsequently, a new D-pi-A electron structure between the Ag
      nanoparticles and the N-containing groups/azobenzene chromophores is created. The
      enhanced internal electric field in the nanoparticles and the strengthened and
      extended pi-conjugation in the new D-pi-A electron structure, lead to the large
      enhancement of optical non-linearity of the hybrid films.

PMID- 19156277
TI  - Galactose oxidase models: insights from 19F NMR spectroscopy.
AB  - (19)F labelled tripodal ligands that possess a N(3)O donor set (one phenol, one
      tertiary amine and either two pyridines or one pyridine and one quinoline) have
      been synthesized. The fluorine is incorporated either at the phenol O-donor
      (HL(F) and HL(CF3)) or at the quinoline N-donor (HLq(OMe) and HLq(NO2)). The
      copper(ii)-phenol complexes (2H)(2+), (1H)(2+), (3H)(2+) and (4H)(2+) as well as
      the corresponding copper(ii)-phenolate complexes have been characterized. X-Ray
      diffraction reveals an increase in the oxygen-copper bond distance of more than
      0.4 A upon protonation of the phenolate moiety of (4)(+). Protonation is
      accompanied by an axial to equatorial isomerization of the quinoline group. DFT
      calculations show that stretching of the Cu-O(phenol) bond, pi-stacking
      interactions and rotation of the pyridine are key steps in this isomerization
      process. Protonation, and thus changes in the oxygen-copper bond distance induce
      either a decrease ((1H)(2+), (2H)(2+)) or an increase ((3H)(2+) and (4H)(2+)) in
      the copper-fluorine distance that could be monitored by (19)F NMR. In the former
      case, a broadening of the (19)F NMR signal is observed, whereas a sharpening is
      observed in the latter case. Temperature dependent (19)F NMR measurements on
      equimolar mixtures of the phenol and phenolate complexes of (3)(+) and (4)(+)
      reveal rate constants for proton transfer and/or isomerization of 3000 +/- 100 s(
      1) and 2900 +/- 100 s(-1), respectively, at the coalescence temperature. This
      temperature was found to be strongly affected by the phenol para-substituent as
      it is 226 K and ca. 330 K for (3)(+) and (4)(+), respectively. A phenoxyl radical
      species ((3 )(2+)) could be generated and characterized for the first time by
      (19)F NMR spectroscopy.

PMID- 19156278
TI  - Lariat ethers with fluoroaryl side-arms: a study of CFmetal cation interaction in
      the complexes of N-(o-fluoroaryl)azacrown ethers.
AB  - New lariat ethers, N-(o-fluorophenyl)aza-15-crown-5 (F-A15C5) and N,N'-bis(o
      fluorophenyl)diaza-18-crown-6 (F(2)-A(2)18C6), were prepared by the N-arylation
      of the corresponding azacrown ethers. The interaction of the ligands with metal
      cations was studied in solution by (1)H and (19)F NMR (in acetone-d(6)) and UV
      spectroscopy (MeOH) confirming the formation of complexes of F(2)-A(2)18C6 with
      K(+), Na(+), Ag(+), Ba(2+), Pb(2+) and of F-A15C5 with Na(+) and giving evidence
      of CFmetal cation interaction. Cation binding constants (beta, evaluated by UV
      titration method), demonstrate that F-A15C5 and F(2)-A(2)18C6 form more stable
      complexes than their fluorine-free analogs. The effect depends on the nature of
      the metal cation and is at a maximum for hard, singly charged cations (up to 3
      logbeta units for K(+) complex of F(2)-A(2)18C6). The X-ray structures of
      complexes [Pb(F(2)-A(2)18C6)(H(2)O)](ClO(4))(2) () and [Ba(F(2)
      A(2)18C6)(ClO(4))(2)] () reveal short Pb-F (2.805 A) and Ba-F (2.965 A) contacts.
      Complex is centrosymmetric (C(i)), while complex has C(2) symmetry with one-side
      coordination of o-fluorophenyl groups to Pb(2+). This "one-side" coordination
      mode of Pb(2+) is indicative of a partial localization of the Pb(2+) lone pair.

PMID- 19156279
TI  - Boron(8) substituted nitrilium and ammonium derivatives, versatile cobalt bis(1,2
      dicarbollide) building blocks for synthetic purposes.
AB  - The reaction of the cobalt bis(dicarbollide)(1-)() ion in the presence of t
      butylbromide, acting as a potent Lewis acid activator, leads to the clean
      substitution of by the N-atom of acetonitrile (or benzonitrile), thus resulting
      in the smooth formation of [(8-RCN)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'
      Co(iii)](0) (R = CH(3) or C(6)H(5)) ( and ). These compounds can serve as
      versatile precursors for the generation of a variety of other synthetically
      useful functional groups. The nitrogen atom of the nitrile C[triple bond, length
      as m-dash]N- bond in and is prone to the facile addition of nucleophiles. Thus,
      alkaline hydrolysis of and in aqueous alcohols furnishes high yields of the
      corresponding B(8)-N-alkylamides [(8-RC(O)=NH)-1,2-C(2)B(9)H(10))(1',2'
      C(2)B(9)H(11))-3,3'-Co(iii)](-), where R = CH(3) or C(6)H(5) ( and ). The
      reactions with butyl and diethyl amine result in the high-yield formation of 8
      alkylamidine derivatives [(8-(3)R(2)RNH-(1)RC[double bond, length as m-dash]N)
      1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co(iii)](0), where (1)R = CH(3),
      (2)R = H, (3)R = C(4)H(9), (), (1)R = C(6)H(5), (2)R = (3)R = C(2)H(5) () or (1)R
      = C(6)H(5), (2)R = (3)R = C(2)H(5) (). Hydrazinolysis of provides a high yield of
      the zwitterionic [(8-H(3)N)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'
      Co(iii)](0) (), whereas reduction of the nitrile group in and using BH(3).SMe(2)
      affords the respective alkylammonium derivatives [(8-RH(2)N)-1,2
      C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co(iii)](0), where R = -C(2)H(5) () or 
      CH(2)C(6)H(5) () in moderate yields. Compound can also be prepared by alkylation
      of along with dibenzylderivative (). A further example of alkylation is the ring
      cleavage of the 3-hydroxypropanesulfonic acid gamma-sultone producing a compound
      with alkyl ammonium sulfonic acid substitution [(8-O(3)SC(3)H(6)NH(2))-1,2
      C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co(iii)](-) () All new compounds were
      characterized by multinuclear NMR spectroscopy and mass spectrometry and the
      structures of compounds , , and were established by X-ray crystallography.

PMID- 19156280
TI  - Synthesis, characterization and catalytic activity of saturated and unsaturated N
      heterocyclic carbene iridium(i) complexes.
AB  - Both saturated and unsaturated N-benzyl substituted heterocyclic carbene (NHC)
      iridum(i) complexes were synthesized. The unsaturated carbene complex [(un-NHC
      Bn)Ir(CO)(2)Cl] in the cis form was prepared via the carbene transfer from the
      corresponding silver complex to [Ir(COD)(2)Cl](2) followed by ligand substitution
      with CO, whereas the saturated complex was obtained via the transfer from (sat
      NHC-Bn)W(CO)(5). The treatment of phosphines with (NHC)Ir(CO)(2)Cl complexes
      yielded the products with the phosphine ligand trans to the carbene moiety via
      substitution. X-Ray structural determination shows that distances of Ir
      C((carbene)) in both (un-NHC-Bn)Ir(CO)(PR(3))Cl and (un-NHC-Bn)Ir(CO)(PR(3))Cl
      are essentially the same. Analyses of spectroscopic and crystal structural data
      of iridium complexes [(NHC)Ir(CO)(PR(3))Cl] and Vaska's complex show similar
      corresponding data in both types of complexes, suggesting that the studied NHC
      ligands and phosphines have similar bonding with Ir(i) metal center. All iridium
      complexes studied in this work illustrated their catalytically activity on N
      alkylation of amine with alcohol via hydrogen transfer reduction. It appears no
      dramatic difference on the catalytic activity among these iridium carbene
      complexes; but the saturated carbene complex (sat-NHC-Bn)Ir(CO)(PR(3))Cl appears
      to be slightly more active. For example, the reaction of benzyl alcohol with
      aniline in the presence of catalyst (1 mol%) under basic conditions at 100
      degrees C provided the secondary amine (N-benzylaniline) in 96% yield.

PMID- 19156281
TI  - Reactions of aquatitanium(II) with hypervalent chromium species.
AB  - Titanium(ii) solutions, prepared by dissolving titanium metal in triflic acid and
      HF, react readily with derivatives of Cr(vi), Cr(v) and Cr(iv). Reductions of
      Cr(vi) and Cr(iv), carried out with [Co(NH(3))(5)Br](2+) as a scavenger for
      Cr(ii), yield no detectable Co(2+), indicating that 2e(-) steps, bypassing Cr(v)
      and Cr(iii), are not operative. Catalysis by Ti(iv) is observed only for
      reduction of Cr(vi). Rates for reduction by Ti(iii) are remarkably similar to
      those for the corresponding reductions by Ti(ii). The addition of Ti(iii) to
      triflic acid and HF results in rapid and quantitative disproportionation to
      Ti(ii) and Ti(iv).

PMID- 19156282
TI  - Polymer producing palladium complexes of unidentate phosphines in the
      methoxycarbonylation of ethene.
AB  - A wide range of unidentate phosphines have been studied as ligands for the
      palladium-catalysed methoxycarbonylation of ethene in the presence of
      methanesulfonic acid using methanol as the solvent. At high phosphine to Pd
      ratios, methyl propanoate is formed at a low rate. However, at P-Pd ratios of 4 :
      1, some unidentate phosphines promote the formation of polyketone with moderate
      rates. Analysis of all the phosphines shows that good electron donating power,
      combined with small size, favours polyketone formation.

PMID- 19156283
TI  - Olefin coordination in copper(I) complexes of bis(2-pyridyl)amine.
AB  - Complexes of the type [Cu(H-dpa)(olefin)]BF4 for ethylene (1), propylene (2), 1
      butene (3), 1-hexene (4), 1-octene (5), cis-2-octene (6), trans-2-octene (7), cis
      3-octene (8), trans-3-octene (9), 2-norbornylene (10), 1,5-cyclooctadiene (11),
      styrene (12), cis-stilbene (13), trans-stilbene (14), and Ph2C=CH2 (15) have been
      prepared and characterized by 1H and 13C NMR, FTIR, and TGA. The crystal
      structures have been determined for compounds 5, 6, 8, and 10-13. With the
      exception of compound 11, copper atoms in each complex are coordinated to the two
      pyridine nitrogen atoms and the appropriate olefin; consistent with a pseudo
      three-coordinate Cu(I) cation. Compound 11 has a second weaker p-interaction
      resulting in a distorted tetrahedral geometry. Steric hindrance between the
      olefin and H-dpa manifests as both a twisting of the olefin out of the plane of
      the H-dpa ligand and a concomitant folding of the H-dpa ligand. The shifts in the
      nN-H IR spectral band for H-dpa ligand are consistent with the formation of N
      H...F hydrogen bonded interactions observed in the crystal structures. The 1H and
      13C NMR spectra of [Cu(H-dpa)(olefin)]BF4 exhibit an upfield shift in the olefin
      signal as compared to free olefin. A comparison of the Dd values for terminal
      olefins shows that the similarity of binding for H2C=CHR (R = CnH2n+1, n = 1-6)
      mitigates any preferential complexation of various terminal olefins using the H
      dpa ligand. For octenes there is a significant difference in binding between a
      terminal and internal olefin, but there is little preference between binding for
      different internal olefins and only a modest difference between the cis and trans
      isomers of the same olefin. A good correlation exists between the 1HNMRDd values
      and the TGA data, confirming that the shift of the olefin NMR resonances upon
      coordination is associated with the binding strength of the complex. Ab initio
      calculations using four different method/basis set combinations on the structure
      of [Cu(H-dpa)(1-octene)]+ were compared with the crystal structure.

PMID- 19156286
TI  - Sub-micron resolution surface plasmon resonance imaging enabled by nanohole
      arrays with surrounding Bragg mirrors for enhanced sensitivity and isolation.
AB  - We present nanohole arrays in thin gold films as sub-micron resolution surface
      plasmon resonance (SPR) imaging pixels in a microarray format. With SPR imaging,
      the resolution is not limited by diffraction, but by the propagation of surface
      plasmon waves to adjacent sensing areas, or nanohole arrays, causing unwanted
      interference. For ultimate scalability, several issues need to be addressed,
      including: (1) as several nanohole arrays are brought close to each other,
      surface plasmon interference introduces large sources of error; and (2) as the
      size of the nanohole array is reduced, i.e. fewer holes, detection sensitivity
      suffers. To address these scalability issues, we surround each biosensing pixel
      (a 3-by-3 nanohole array) with plasmonic Bragg mirrors, blocking interference
      between adjacent SPR sensing pixels for high-density packing, while maintaining
      the sensitivity of a 50 x larger footprint pixel (a 16-by-16 nanohole array). We
      measure real-time, label-free streptavidin-biotin binding kinetics with a
      microarray of 600 sub-micron biosensing pixels at a packing density of more than
      10(7) per cm(2).

PMID- 19156287
TI  - Liquid-liquid phase separation: characterisation of a novel device capable of
      separating particle carrying multiphase flows.
AB  - Capillary forces on the microscale are exploited to create a continuous flow
      liquid-liquid phase separator. Segmented flow regimes of immiscible fluids are
      generated and subsequently separated into their component phases through an array
      of high aspect ratio, laser machined, separation ducts (36 microm wide, 130
      microm deep) in a planar, integrated, polytetrafluoroethylene (PTFE) microdevice.
      A controlled pressure differential across the phase separator architecture
      facilitates the selective passage of the wetting, organic, phase through the
      separator ducts, enabling separation of microfluidic multiphase flow streams. The
      reported device is demonstrated to separate water and chloroform segmented flow
      regimes at flow rates up to 0.4 ml min(-1). Separation efficiency is quantified
      over a range of flow rates and applied pressure differentials, characterising
      device behaviour and limits of operation. Experimental measurements and
      observations are supported by theoretical hydrodynamic and capillary pressure
      modelling. The influence of material properties and geometric design parameters
      on phase separation is quantified and optimisation strategies proposed. The novel
      ability of the membrane free device to separate an organic phase containing
      suspended microparticulates, from an aqueous phase, is also demonstrated.

PMID- 19156288
TI  - A cooperative polymer-DNA microarray approach to biomaterial investigation.
AB  - In this study, polymer microarrays were used for the rapid identification of
      polymer substrates upon which a suspension cell line would both adhere and
      proliferate giving a detailed and rapid understanding of cell-biomaterial
      interactions. Analysis demonstrated that suspension K562 human erythroleukemic
      cells, which normally grow in suspension, adhered and proliferated on several
      different polymers. Phenotypic and transcriptomic analysis techniques allowed
      examination of the interaction between cells and polymers permitting the
      elucidation of putative links between phenotypic responses to cell-biomaterial
      interactions and global gene expression.

PMID- 19156289
TI  - Novel MEA platform with PDMS microtunnels enables the detection of action
      potential propagation from isolated axons in culture.
AB  - This study investigated a novel multi-electrode-array (MEA) design capable of
      long-term and highly selective recordings of axonal signals using PDMS
      microtunnels. We successfully grew neurons in culture so that only axons extended
      through narrow (10 microm wide by 3 microm high) and long (750 microm)
      microtunnels under which multiple electrodes were integrated. This permitted the
      recording of relatively large (up to 200 microV) electrical signals, including
      the propagation speed and direction of these travelling action potentials. To
      further demonstrate the operation of the device as a diagnostic tool for drug
      screening assays, the drug mepivacaine was applied in washout experiments. Here,
      we identified significant changes in mean spiking rate and conduction velocity.

PMID- 19156290
TI  - A conformal nano-adhesive via initiated chemical vapor deposition for
      microfluidic devices.
AB  - A novel high-strength nano-adhesive is demonstrated for fabricating nano- and
      microfluidic devices. While the traditional plasma sealing methods are specific
      for sealing glass to poly(dimethylsiloxane) (PDMS), the new method is compatible
      with a wide variety of polymeric and inorganic materials, including flexible
      substrates. Additionally, the traditional method requires that sealing occur
      within minutes after the plasma treatment. In contrast, the individual parts
      treated with the nano-adhesive could be aged for at least three months prior to
      joining with no measurable deterioration of post-cure adhesive strength. The nano
      adhesive is comprised of a complementary pair of polymeric nanolayers. An epoxy
      containing polymer, poly(glycidyl methacrylate) (PGMA) was grown via initiated
      chemical vapor deposition (iCVD) on the substrate containing the channels. A
      plasma polymerized polyallylamine (PAAm) layer was grown on the opposing flat
      surface. Both CVD monomers are commercially available. The PGMA nano-adhesive
      layer displayed conformal coverage over the channels and was firmly tethered to
      the substrate. Contacting the complementary PGMA and PAAm surfaces, followed by
      curing at 70 degrees C, resulted in nano- and micro-channel structures. The
      formation of the covalent tethers between the complementary surfaces produces no
      gaseous by-products which would need to outgas. The nano-adhesive layers did not
      flow significantly as a result of curing, allowing the cross-sectional profile of
      the channel to be maintained. This enabled fabrication of channels with widths as
      small as 200 nm. Seals able to withstand > 50 psia were fabricated employing many
      types of substrates, including silicon wafer, glass, quartz, PDMS, polystyrene
      petri dishes, poly(ethylene terephthalate) (PET), polycarbonate (PC), and
      poly(tetrafluoro ethylene) (PTFE).

PMID- 19156292
TI  - Controlled cocultures of HeLa cells and human umbilical vein endothelial cells on
      detachable substrates.
AB  - We investigated the interactions between HeLa cells and human umbilical vein
      endothelial cells (HUVECs) by monitoring their movements in a controllable
      coculture system. Two complementary, detachable, cell-substrates, one of
      polystyrene (PS) and the other of poly(dimethylsiloxane) (PDMS), were fabricated
      by replica molding. Coculturing was started by mechanically assembling two
      complementary substrates. One substrate was covered with a confluent layer of
      HeLa cells and its complement covered with confluent HUVECs. Using this coculture
      system as a tumor/endothelium model, we found that the HeLa cells migrated
      towards the HUVECs, while, simultaneously, the HUVECs retreated and that both
      types of cells migrated approximately twice as rapidly (two hundred microns per
      twenty-four hours) as they did alone. Additionally, when direct contact between
      the two cell types was prevented, the HUVECs initially migrated towards the HeLa
      cells and then retreated. The characteristics of the cell movements, i.e.
      direction and speed, probably are consequences of cell-cell signaling, with such
      signals possibly important during tumor cell intra- and extravasation.

PMID- 19156291
TI  - A multi-purpose microfluidic perfusion system with combinatorial choice of
      inputs, mixtures, gradient patterns, and flow rates.
AB  - Microfluidic perfusion systems, characterized by deterministic flow, low reagent
      consumption, small dead volumes, large integration in small footprints, high
      throughput operation, and low-cost fabrication, are being increasingly used for
      cell culture studies in applications such as basic cell biology, molecular
      biological assays, tissue engineering, and systems biology. We report a
      multipurpose, pressure-driven and computer-controlled microfluidic perfusion
      device containing sixteen inlets and a large cell culture chamber. The user can
      choose, with sub-second temporal resolution, (a) to feed the chamber with one of
      16 inlets, all 16 inlets, or one of 64 combinations of 2, 4, or 8 inlets using a
      binary multiplexer; (b) to introduce into the chamber a heterogeneous laminar
      flow of the inlets, a smoothened gradient, or a fully homogenized mixture; (c) to
      bypass the chamber in order to purge the inlet lines so as to minimize the dead
      volume; (d) to generate asymmetrical and curvilinear flow patterns within the
      chamber by opening side outlets; and (e) to slow down the flow by combinatorially
      adding segments of high fluid resistance (sixteen different levels of flow rates
      are possible using only four valves). All functionalities are combined to create
      complex gradient patterns and sequential perfusions within the central chamber.

PMID- 19156293
TI  - Enhanced on-chip SERS based biomolecular detection using electrokinetically
      active microwells.
AB  - Here we present a novel microfluidic technique for on-chip surface enhanced Raman
      spectroscopy (SERS) based biomolecular detection, exploiting the use of
      electrokinetically active microwells. Briefly, the chip comprises of a series of
      microfluidic channels containing embedded microwells that, when electrically
      actuated, either locally attract or repulse species from solution through a
      combination of electrokinetic effects. We demonstrate that the approach combines
      the advantages of existing homogeneous (solution phase) and heterogeneous
      (surface phase) on-chip techniques by enabling active mixing to enhance the rate
      of binding between the SERS enhancers and the biomolecular targets as well as
      rapid concentration of the product for surface phase optical interrogation. This
      paper describes the chip design and fabrication procedure, experimental results
      illustrating the optimal conditions for our concentration and mixing processes,
      and a numerical analysis of the flow pattern. To demonstrate the usefulness of
      the device we apply it to the quantitative detection of nucleic acid sequences
      associated with Dengue virus serotype 2. We report a limit of detection for
      Dengue sequences of 30 pM and show excellent specificity against other serotypes.

PMID- 19156294
TI  - Sandwich mixer-reactor: influence of the diffusion coefficient and flow rate
      ratios.
AB  - A sandwich mixer consists of mixing two solutions in a channel, one central
      laminar flow being sandwiched between two outer flow solutions. The present
      numerical study considers the convection-diffusion of two reacting species A and
      B, provided respectively by the two incoming solutions. The simulations show how
      the diffusion coefficient, flow rate and species concentration ratios influence,
      via the transversal diffusion length and reaction kinetics, the reaction extent
      at the end of the sandwich mixer. First, this extent can be enhanced up to 60% if
      the species with the lowest diffusion coefficient is located in the outer
      solutions where the flow velocity is small compared to that of the central part
      (higher residence time). Secondly, decreasing the outer flow rates (to confine
      the reaction close to the walls) and increasing the local concentration to keep
      the same flux ratio improve the extent by 300%. Comparison with a bi-lamination
      passive mixer, with an ideal mixer and an electro-osmotic driven flow mixer is
      presented. These conclusions are also demonstrated for consecutive reactions,
      showing an amplification of the effects described above. The results are also
      presented versus the residence time in the mixer-reactor to show the time window
      for which the gain is appreciable.

PMID- 19156295
TI  - Nanostructured biosensing platform-shadow edge lithography for high-throughput
      nanofabrication.
AB  - One of the critical challenges in nanostructured biosensors is to manufacture an
      addressable array of nanopatterns at low cost. The addressable array (1) provides
      multiplexing for biomolecule detection and (2) enables direct detection of
      biomolecules without labeling and amplification. To fabricate such an array of
      nanostructures, current nanolithography methods are limited by the lack of either
      high throughput or high resolution. This paper presents a high-resolution and
      high-throughput nanolithography method using the compensated shadow effect in
      high-vacuum evaporation. The approach enables the fabrication of uniform nanogaps
      down to 20 nm in width across a 100 mm silicon wafer. The nanogap pattern is used
      as a template for the routine fabrication of zero-, one-, and two-dimensional
      nanostructures with a high yield. The method can facilitate the fabrication of
      nanostructured biosensors on a wafer scale at a low manufacturing cost.

PMID- 19156296
TI  - Characterization of porous silicon integrated in liquid chromatography chips.
AB  - Properties of porous silicon which are relevant for use of the material as a
      stationary phase in liquid chromatography chips, like porosity, pore size and
      specific surface area, were determined with high-resolution SEM and N(2)
      adsorption-desorption isotherms. For the anodization conditions investigated,
      porosity is between 20 and 60%, pore sizes between 2 and 5 nm and specific
      surface area between 130 and 410 m(2)/cm(3). It was established that under
      identical anodization conditions, porous layer formation is 10-15% slower on
      micromachined pillars than on flat substrates, and depends on geometrical
      parameters like pillar diameter and height and interpillar spacing. In
      microchannels containing pillars with a porous silicon shell, chromatographic
      experiments on a coumarin dye mixture were performed, which in comparison with
      non-porous pillars showed a significant increase of the retention factors,
      resulting from the large internal surface of the porous pillars. The increased
      relative retention of one of the coumarin dyes, C480, could be correlated
      quantitatively with the measured internal surface of the porous layer. Due to the
      small pore size, these porous shell columns are particularly suitable for
      analytical or preparative separation of low-molecular weight molecules, with
      applications in metabolomics, food quality control, or medical diagnostics.

PMID- 19156297
TI  - Spatial distribution of laminar flow-assisted dendritic amplification.
AB  - In this paper, we report spatial distribution of laminar flow-assisted dendritic
      amplification (LFDA) product. LFDA is a recently invented signal amplification
      method dedicated to biomolecular binding events on microchannel walls. Onto the
      bound biomolecule, a dendritic structure is constructed by supplying two building
      blocks from laminar streams produced by a Y-shaped microchannel. In view of the
      extension of LFDA to simultaneous amplification of multiple binding spots, we
      have investigated the distribution of the LFDA product across and along the
      microchannel with the course of time. We fabricated a Y-shaped microchannel with
      a cross section of 110 microm x 22 microm using poly(dimethylsiloxane). As the
      LFDA building blocks, FITC-labeled streptavidin and biotinylated anti
      streptavidin were injected from the two inlets of the microchannel at a mean flow
      velocity of 6.2 mm s(-1) (after the confluence). Nonspecific adsorption of the
      building blocks formed the seed layer of LFDA. The progress of LFDA was monitored
      with a fluorescence microscope up to 10.1 mm of microchannel length. After 5 min
      or later, the fluorescence intensity profile across the microchannel showed a
      peak at the center of the channel. With the course of time, the peak height grew
      exponentially except for slight saturation, but the peak width was almost
      constant. Along the microchannel, the peak height decreased almost linearly with
      the increasing logarithm of the distance, and the peak width was broadened in
      accordance with the 1/3 power law.

PMID- 19156298
TI  - A screw-actuated pneumatic valve for portable, disposable microfluidics.
AB  - This work describes a simple and inexpensive approach for controlling the
      pneumatic valves that were invented in Quake's group to miniaturize the whole
      system for portable and disposable microfluidic devices. The valves are assembled
      from two parts. One is the polydimethylsiloxane (PDMS) channels formed by
      multilayer soft lithography. The other is a polymethylmethacrylate (PMMA) frame
      with machine screws for pressure control. Turning the screws into the control
      channel inlet (filled with water and covered with a thin PDMS membrane) actuates
      the valve by creating pressure in the control channel. This method avoids the
      bulky and expensive external pressure-control facilities and can be easily
      integrated into portable and disposable devices.

PMID- 19156299
TI  - Two-dimensional droplet-based surface plasmon resonance imaging using
      electrowetting-on-dielectric microfluidics.
AB  - This article presents a multichannel droplet-based surface plasmon resonance
      platform. The platform comprises a digital electrowetting-on-dielectric (EWOD)
      microfluidic device coupled to surface plasmon resonance imaging (SPRi). SPRi is
      now a well-established detection technique that enables in-situ monitoring of
      multiple reactions occurring at the surface of the chip without the use of
      labels. Currently, the limiting factor in the application of SPRi for high
      throughput applications is the flow-cell technology which relies on sequential
      sample processing within the continuous fluid flow. An original solution compared
      to the continuous flow-cell technology is proposed to increase the capability of
      existing SPRi technology. A parallel SPRi detection of different samples on the
      surface is achieved using the array-based digital microfluidic device.

PMID- 19156300
TI  - Absolute brightness of fluorescent microspheres.
AB  - The absolute brightness of fluorescent particles, such as dye-containing nano-
      and microspheres or quantum dots, is a critical design parameter for many
      applications relying on fluorescence detection. The absolute brightness, defined
      as the ratio of radiant intensity of emission to illumination intensity of
      excitation, of nile-red fluorescent microspheres with a 1 micrometre diameter is
      measured to be 4.2 +/- 1 x 10(-16) m(2)/sr, and the implications for the design
      of kinesin motor protein-powered "smart dust" devices and the remote detection of
      fluorescence are discussed.

PMID- 19156301
TI  - Effective mixing in a microfluidic chip using magnetic particles.
AB  - We present a novel active mixing method in a microfluidic chip, where the
      controlled stirring of magnetic particles is used to achieve an effective mixing
      of fluids. To perform mixing, the ferromagnetic particles were embedded and
      manipulated under the influence of a rotating magnetic field. By aligning the
      magnetic beads along the magnetic field lines, rod-like structures are formed,
      functioning as small stir bars. Under higher flow conditions the particles did
      not form the typical rod structure but rather formed aggregates, which were even
      more beneficial for mixing. Our system reached a 96% mixing efficiency in a
      relatively short distance (800 microm) at a flow rate of 1.2-4.8 mm/s. These
      results demonstrate that our mixing method is useful for microfluidic devices
      with low aspect ratios and molecules with large molecular weights.

PMID- 19156302
TI  - Interlocked host rotaxane and catenane structures for sensing charged guest
      species via optical and electrochemical methodologies.
AB  - The potential of interlocked host rotaxane and catenane structures as innovative
      optical and electrochemical sensors is highlighted. Interlocked structures can be
      engineered to bind specific guests within the topologically constrained three
      dimensional cavities created during their template-driven syntheses. This binding
      ability, when coupled to the signal transduction capabilities associated with
      appended reporter groups and their dynamic structures, make catenanes and
      rotaxanes highly promising candidates for the development of molecular sensors.
      With the ultimate challenge of fabricating highly selective anion sensing
      configurations, a three-staged strategy has been followed. First, we developed a
      general anion templation methodology for the construction of a variety of
      interpenetrated and interlocked molecular structures. [2]Rotaxanes and
      [2]catenanes synthesised using this novel protocol show, after template removal,
      favourable selective anion binding characteristics distinct from their separate
      components. At the second stage, the incorporation of redox- and photo-active
      groups into these interlocked frameworks converts them into
      electrochemical/optical molecular sensors. In the final third stage, the
      confinement of interlocked anion receptors at surfaces results in the fabrication
      of devices exhibiting highly selective binding and electrochemical and/or optical
      sensing behaviour.

PMID- 19156303
TI  - First total synthesis of (-)-caulerpenynol.
AB  - The first diastereoselective synthesis of the antimicrobial and cytotoxic agent (
      )-caulerpenynol has been achieved in relatively few steps from the commercially
      available (S)-malic acid.

PMID- 19156304
TI  - NbCl(3)-catalyzed [2+2+2] intermolecular cycloaddition of alkynes and alkenes to
      1,3-cyclohexadiene derivatives.
AB  - NbCl(3)(DME)-catalyzed [2+2+2] intermolecular cycloaddition of alkynes and
      alkenes was successfully achieved to give 1,4,5-trisubstituted-1,3-cyclohexadiene
      derivatives in good yields.

PMID- 19156305
TI  - Tandem copper-catalysed aryl and alkenyl amination reactions: the synthesis of N
      functionalised indoles.
AB  - A Cu-diamine complex effectively catalyses tandem C-N bond formation on 2-(2
      haloalkenyl)-aryl halide substrates, to deliver a series of N-functionalised
      indoles. Anilines, amides and carbamates are all effective coupling partners
      under the developed conditions.

PMID- 19156306
TI  - A chemical epigenetics approach for engineering the in situ biosynthesis of a
      cryptic natural product from Aspergillus niger.
AB  - A new fungal metabolite, nygerone A (), featuring a unique 1-phenylpyridin-4(1H)
      one core that had previously not been reported from any natural source, has been
      obtained from Aspergillus niger using a chemical epigenetics methodology.

PMID- 19156307
TI  - Reductive demetallation of Cu-corroles--a new protective strategy towards
      functional free-base corroles.
AB  - A novel procedure for the reductive demetallation of Cu-meso-triarylcorroles has
      been disclosed. The reversible sequence copper metallation/demetallation was
      proven to be an effective protection/deprotection strategy towards sophisticated
      functionalized free-base corroles.

PMID- 19156308
TI  - First Y-type actinomycins from Streptomyces with divergent structure-activity
      relationships for antibacterial and cytotoxic properties.
AB  - Streptomyces sp. strain Go-GS12 was found to produce five novel actinomycins Y(1)
      Y(5) (). Their amino acid pattern discloses them as members of a new family of
      this important class of antibiotics. Compounds differ from Z-type actinomycins in
      their beta-peptidolactone rings which here contain trans-4-hydroxyproline (Hyp)
      or 4-oxoproline (OPro) amino acids, and from the X-congeners by containing
      methylalanine (MeAla). Within the new Y-type actinomycins variations are not only
      in the rare chlorinated or hydroxylated threonine residue. Furthermore, the beta
      ring can undergo rearrangement by a two-fold acyl shift (compounds and ) or show
      a unique additional ring closure with the chromophore (compound ), resulting in
      metabolites with yet unknown structural motifs, altered conformations and
      distinct bioactivities. The strongest bioactivity was found for the chlorine
      containing actinomycin Y(1) (), the most surprising for Y(5) () with cytotoxic
      and antibacterial effects losing their coherence, which has been observed for the
      first time here.

PMID- 19156309
TI  - High yield detritylation of surface-attached nucleosides with photoacid generated
      in an overlying solid film: roles of translational diffusion and scavenging.
AB  - Conventional solid-phase oligonucleotide synthesis overcomes the reversibility of
      acid-dependent detritylation by washing away the released dimethoxytrityl cations
      (DMT(+)) with acid. This option is unavailable if the acid is photogenerated in
      an overlying solid film, as in the photolithographic fabrication of
      oligonucleotide arrays on planar surfaces. To overcome the resulting
      reversibility problem we developed methods of achieving >or=98% detritylation of
      glass-attached 5'-O-DMT-thymidine, a model for 5'-O-DMT-protected
      oligonucleotides, by the photogeneration of trichloroacetic acid in a solid film.
      Enhanced intrafilm diffusion, insufficient to degrade the photolithographic
      resolution but enabling DMT(+) to move from its plane of release into the
      overlying photoacid-generating film, increased detritylation from <or=30% to
      >or=98%. Inclusion of an intrafilm carbocation scavenger such as a triarylsilane
      hydride converted the detritylation into a time-dependent irreversible process
      proceeding to >or=99% detritylation within 60 s following brief photoacid
      generation. Light sensitivity is high, exceeding direct photodeprotection methods
      by 15-100 fold.

PMID- 19156310
TI  - Computational mutagenesis reveals the role of active-site tyrosine in stabilising
      a boat conformation for the substrate: QM/MM molecular dynamics studies of wild
      type and mutant xylanases.
AB  - Molecular dynamics simulations have been performed for non-covalent complexes of
      phenyl beta-xylobioside with the retaining endo-beta-1,4-xylanase from B.
      circulans (BCX) and its Tyr69Phe mutant using a hybrid QM/MM methodology. A
      trajectory initiated for the wild-type enzyme-substrate complex with the proximal
      xylose ring bound at the -1 subsite (adjacent to the scissile glycosidic bond) in
      the (4)C(1) chair conformation shows spontaneous transformation to the (2,5)B
      boat conformation, and potential of mean force calculations indicate that the
      boat is approximately 30 kJ mol(-1) lower in free energy than the chair.
      Analogous simulations for the mutant lacking one oxygen atom confirm the key role
      of Tyr69 in stabilizing the boat in preference to the (4)C(1) chair conformation,
      with a relative free energy difference of about 20 kJ mol(-1), by donating a
      hydrogen bond to the endocyclic oxygen of the proximal xylose ring. QM/MM MD
      simulations for phenyl beta-xyloside in water, with and without a
      propionate/propionic acid pair to mimic the catalytic glutamate/glutamic acid
      pair of the enzyme, show the (4)C(1) chair to be stable, although a hydrogen bond
      between the OH group at C2 of xylose and the propionate moiety seems to provide
      some stabilization for the (2,5)B conformation.

PMID- 19156311
TI  - First synthesis and electronic properties of diphenothiazine dumbbells bridged by
      heterocycles.
AB  - According to cyclic voltammetry, symmetrical dumbbell-shaped phenothiazine dyads
      bridged by heterocycles show intense electronic coupling between the redox-active
      phenothiazine moieties. Furthermore, the fluorescence of the pyridyl-bridged
      derivatives can be controlled by pH change giving reversibly switchable redox
      active biselectrophore dyads.

PMID- 19156312
TI  - Metal-mediated base pairing within the simplified nucleic acid GNA.
AB  - Hydroxypyridone and pyridopurine homo- and hetero-base pairs have been
      investigated in the context of duplex GNA (glycol nucleic acid). Phosphoramidites
      for automated GNA solid phase synthesis were synthesized economically in a few
      steps starting from commercially available enantiopure glycidol. Similar to their
      behavior in DNA, the hydroxypyridone and pyridopurine homo-base pairs display a
      metal-dependent base pairing, with the hydroxypyridone base pair exhibiting a
      preference for copper(II) ions and the pyridopurine a preference for nickel(II)
      ions. However, these metallo-base pairs show modulated properties in GNA with
      respect to metal-dependent pairing stabilities and metal selectivities. Most
      interestingly, the hydroxypyridone homo-base pair and hydroxypyridone
      pyridopurine hetero-base pair are particularly well accommodated in the GNA
      duplex and form copper(II)-dependent base pairs that are more stable compared to
      a Watson-Crick A:T base pair at the same position by nearly 20 degrees C and 24
      degrees C, respectively. The structure of the copper(II)-hydroxypyridone homo
      base pair is discussed based on a recent metallo-GNA duplex crystal structure.

PMID- 19156313
TI  - What is the mechanism of amine conjugate additions to pyrazole crotonate
      catalyzed by thiourea catalysts?
AB  - Aminoindanol-derived thioureas catalyze proton transfer and do not stabilise
      anions in an asymmetric conjugate addition to pyrazole crotonate. Calculations
      show that the urea H-bonds play different roles in the preferred transition state
      and in the one leading to the minor enantiomer in the mechanism of hydroxy
      thiourea catalyzed conjugate additions to pyrazole crotonates.

PMID- 19156314
TI  - A systematic approach to forming micro-contact imprints of creatine kinase.
AB  - A systematic approach has been used to form molecular imprints of creatine kinase
      (CK) using micro-contact imprinting. Using thermocalorimetry data, we selected
      poly(ethylene glycol) 400 dimethacrylate (PEG400DMA) as our crosslinker, on the
      basis that it would be expected to have minimal specific recognition when
      incorporated into the imprinted polymer. The functional monomer used, methacrylic
      acid (MAA), was chosen from a panel of six candidates on the basis of it giving
      the highest differential affinity with respect to a non-imprinted polymer. A
      polymer formed with 5% MAA and 95% PEG400DMA showed excellent imprint
      recognition, with CK binding to the imprinted material being 2.05 +/- 0.07 x 10(
      10) mol cm(-2) compared to 9.1 +/- 4.5 x 10(-12) mol cm(-2) control binding. The
      imprinted polymers (approximate thickness 22.6 mum as measured by Alpha-step)
      showed clear two-phase binding with maximum absorption achieved after
      approximately 2 hours. Data extracted from Scatchard plots showed the K(d) for
      the high affinity binding site population to be 2.56 x 10(-10) M and the binding
      site population to be 1.97 x 10(-10) mol cm(-2), corresponding data for low
      affinity binding sites shows the K(d) = 3.27 x 10(-9) M and the binding site
      population to be 2.32 x 10(-10) mol cm(-2). Re-binding the molecularly imprinted
      polymers (MIPs) with non-template proteins, namely myoglobin, human serum albumin
      (HSA) and immunoglobulin G (Ig G), showed these proteins to have comparatively
      little affinity for the CK imprinted films. The percentage re-binding figures,
      relative to CK binding, were: 18.7, 3.5, and 3.5 for myoglobin, HSA, and Ig G
      respectively. This pattern of binding was maintained in competitive binding
      protocols with two proteins in solution at equal concentrations, where the
      percentage re-binding figures, relative to CK binding (4.5 +/- 0.06 x 10(-10) mol
      cm(-2)), were 17.2, 4.5, and 2.9 for myoglobin, HSA, and Ig G respectively. The
      presence of multiple competing analytes in undiluted human serum did not
      significantly decrease template protein recognition. Finally, we used circular
      dichroism to monitor protein denaturation, and showed that the denatured template
      protein loses a significant proportion (76.8%) of its MIP affinity after being
      heated at 80 degrees C for 10 minutes.

PMID- 19156315
TI  - Synthesis of a resorcinarene-based tetraphosphine-cavitand and its use in Heck
      reactions.
AB  - A resorcinarene cavitand substituted by four -CH(2)PPh(2) pendant arms was
      synthesised starting from a generic C(5)-resorcinarene. Combining this
      tetraphosphine with palladium acetate and Cs(2)CO(3) gave an active Heck
      catalyst. The highest activities were observed by using a tetraphosphine/Pd ratio
      of ca. 1:1.

PMID- 19156316
TI  - Ring-opening reaction of Bus- and SES-protected aziridines using lithiated
      dithianes.
AB  - The scope and limitation of the ring-opening reaction of sulfonyl-activated
      aziridines using lithiated dithianes was investigated. Nucleophilic attack of
      lithiated dithianes on aziridines containing tert-butylsulfonyl (Bus) and 2
      (trimethylsilyl)ethylsulfonyl (SES) demonstrated efficient ring cleavage to yield
      beta-amino carbonyl equivalents, gamma-lactam and syn- and anti-1,5
      aminoalcohols. The first example of a ring-opening reaction of di-substituted
      aziridine using dithiane is also reported. Finally, the Bus and SES-possessing
      dithianes obtained were deprotected to demonstrate their synthetic usefulness.

PMID- 19156317
TI  - Bismuth triflate-catalyzed Wagner-Meerwein rearrangement in terpenes. Application
      to the synthesis of the 18alpha-oleanane core and A-neo-18alpha-oleanene
      compounds from lupanes.
AB  - The use of bismuth(III) salts as catalysts for the Wagner-Meerwein rearrangement
      of lupane derivatives with expansion of ring E and formation of an additional O
      containing ring is reported. This process has also been extended to other
      terpenes, such as the sesquiterpene (-)-caryophyllene oxide. When the reaction
      was performed with oleanonic acid, 28,13beta-lactonization occurred, without
      Wagner-Meerwein rearrangement. Under more vigorous reaction conditions,
      dehydration of the 3beta-hydroxyl group and subsequent additional Wagner-Meerwein
      rearrangement led to the selective synthesis of A-neo-18alpha-oleanene compounds,
      in very high yields.

PMID- 19156318
TI  - Kinetic and thermodynamic control in the stereoselective formation of trans- and
      cis-2-ferrocenyl-3-pivaloyl-4-alkyl-1,3-oxazolidin-5-ones.
AB  - A range of ferrocenylimines derived from ferrocenecarboxaldehyde and the alpha
      amino acids (S)-alanine, (S)-2-aminobutyric acid, (S)-norvaline, (R)-2
      phenylglycine, (S)-phenylalanine, O-benzyl (S)-serine, and (S)-tryptophan can be
      cyclised stereoselectively to afford either the corresponding cis- or trans-2
      ferrocenyl-3-pivaloyl-4-alkyl-1,3-oxazolidin-5-ones. The cyclisation reaction
      shows marked temperature dependence, giving rise preferentially to the trans
      oxazolidinone under kinetic control (-78 degrees C) and the thermodynamic cis
      oxazolidinone at -15 degrees C to rt.

PMID- 19156319
TI  - Stereoselective functionalisation of cis- and trans-2-ferrocenyl-3-pivaloyl-4
      alkyl-1,3-oxazolidin-5-ones: asymmetric synthesis of (R)- and (S)-2-alkyl-2
      aminopent-4-enoic acids and (2R,3S)-2-amino-2-methyl-3-hydroxy-3-phenylpropanoic
      acid.
AB  - Treatment of a range of cis- and trans-2-ferrocenyl-3-pivaloyl-4-alkyl-1,3
      oxazolidin-5-ones with LDA followed by the addition of allyl bromide promotes
      highly stereoselective allylation (>98% de) at the 4-position of the
      oxazolidinone ring anti to the stereodirecting 2-ferrocenyl group. Hydrolysis of
      the resultant 4,4-disubstituted oxazolidinones (>98% de) yields enantiomeric (R)-
      and (S)-2-alkyl-2-aminopent-4-enoic acids in high ee. Furthermore, the aldol
      reaction of the lithium enolate of cis-2-ferrocenyl-3-pivaloyl-4-methyl-1,3
      oxazolidin-5-one with benzaldehyde followed by in situ O-protection affords O
      protected aldol products in >98% de, with hydrolysis affording (2R,3S)-2-amino-2
      methyl-3-hydroxy-3-phenylpropanoic acid in >98% de.

PMID- 19156320
TI  - NMR and molecular modeling of the dimeric self-association of the enantiomers of
      1,1'-bi-2-naphthol and 1-phenyl-2,2,2-trifluoroethanol in the solution state and
      their relevance to enantiomer self-disproportionation on achiral-phase
      chromatography (ESDAC).
AB  - Molecular modeling of the homo- and heterochiral dimeric self-associates of the
      enantiomers of 1,1'-bi-2-naphthol and 1-phenyl-2,2,2-trifluoroethanol in solution
      has been performed in order to understand their NMR behavior and in light of the
      phenomenon of "enantiomer self-disproportionation on achiral-phase
      chromatography" (ESDAC). For 1,1'-bi-2-naphthol in C(6)D(6), distinct NMR signals
      for each enantiomer arise for some spins in non-racemic mixtures-the phenomenon
      of self-induced diastereomeric anisochronism (SIDA). The linear divergence of
      these split signals across an enantiomeric titration (a series of samples in
      which the percentage of one enantiomer is varied from 50-100% whilst maintaining
      a constant total concentration), as well as the near linear migration of certain
      signals in CDCl(3) across a similar enantiomeric titration, where signals were
      not observed to be split, is consistent with the calculated small energy
      differences between the homo- and heterochiral associates. For an enantiomeric
      titration of 1-phenyl-2,2,2-trifluoroethanol in n-hexane, NMR signals also
      remained unsplit but the noticeable migration of some revealed a skew indicative
      of a preference for the heterochiral associate. This was duly reflected in the
      calculations which provided a DeltaG value favoring the heterochiral associate by
      2.4 kJ mol(-1). The relevance of these results to evaluating the likely
      occurrence of ESDAC is considered.

PMID- 19156321
TI  - Synthesis and use of isotope-labelled substrates for a mechanistic study on human
      alpha-methylacyl-CoA racemase 1A (AMACR; P504S).
AB  - Alpha-Methylacyl-CoA racemase (AMACR) is an important enzyme for the metabolism
      of branched-chain lipids and drugs. The enzyme is over-expressed in prostate and
      other cancers. AMACR 1A, the major splice variant, was purified from recombinant
      E. coli cells as a His-tag protein. Purified enzyme catalysed chiral inversion of
      both S- and R-2-methyldecanoyl-CoA, with an equilibrium constant of 1.09 +/- 0.14
      (2S/2R). Reactions with (2)H-labelled substrate showed that loss of the alpha
      proton was a prerequisite for chiral inversion. Reactions conducted in (2)H(2)O
      indicated that reprotonation was not stereospecific. These results are the first
      mechanistic study on any recombinant mammalian alpha-methylacyl-CoA racemase.

PMID- 19156322
TI  - Organocatalysis by bimacrocyclic NHCs: unexpected formation of a cyclic
      hemiacetal instead of a gamma-butyrolactone.
AB  - Two bimacrocyclic imidazolinium salts of different size, precursors to respective
      NHCs (N-heterocyclic carbenes), were tested as precatalysts in the reaction of
      aromatic aldehydes or ketones with enals. The expected lactones were produced in
      most cases, but in the reaction of methyl 4-formylbenzoate with cinnamaldehyde,
      the larger bimacrocycle led to the formation of a cyclic hemiacetal, while the
      smaller bimacrocycle gave the anticipated lactone.

PMID- 19156323
TI  - An efficient and chemoselective synthesis of benzo[e][1,4]thiazepin-2(1H,3H,5H)
      ones via a microwave-assisted multi-component reaction in water.
AB  - A new and efficient strategy for the synthesis of benzo[e][1,4]thiazepin
      2(1H,3H,5H)-ones via a microwave-assisted multi-component reaction in aqueous
      media is described.

PMID- 19156324
TI  - Synthesis of the positron-emitting radiotracer [(18)F]-2-fluoro-2-deoxy-D-glucose
      from resin-bound perfluoroalkylsulfonates.
AB  - A new approach to the synthesis of 2-fluoro-2-deoxy-d-glucose (FDG, [(19/18)F]-)
      is described, which employs supported perfluoroalkylsulfonate precursors , where
      the support consists of insoluble polystyrene resin beads. Treatment of these
      resins with [(19)F]fluoride ion afforded protected FDG [(19)F]- as the major
      product, and the identities of the main byproducts were determined. Acidic
      removal of the acetal protecting groups from [(19)F]- was shown to produce
      [(19)F]FDG. The method has been applied to the efficient radiosynthesis of the
      imaging agent [(18)F]FDG, and was shown to produce the radiochemical tracer in
      good radiochemical yield (average 73%, decay corrected).

PMID- 19156325
TI  - Production of carbohydrate building blocks from red seaweed polysaccharides.
      Efficient conversion of galactans into C-glycosyl aldehydes.
AB  - Agarans and carrageenans are abundant natural polysaccharides which are obtained
      on a large scale by water extraction from a variety of red seaweeds. These
      galactans, in addition to being valuable products for the pharmaceutical and food
      industries, are low cost starting materials for the preparation of useful and
      rare carbohydrate-based building blocks whose access by total synthesis is
      difficult and expensive. The semisynthesis of two sets of C-glycosyl aldehydes
      with l- and d-configuration from agarose and kappa-carrageenan respectively is
      described. Succinctly, the partial acid-catalyzed mercaptolysis of the two
      galactans under mild conditions afforded agarobiose and carrabiose (beta-d-Galp
      (1-->4)-3,6-anhydro-aldehydo-l- and d-galactose, respectively) derivatives.
      Complete depolymerization of agarose and kappa-carrageenan under harsher
      conditions produced 3,6-anhydro l- and d-galactose aldehyde derivatives. Chain
      shortening of these products via alditol formation and oxidative carbon-carbon
      bond cleavage furnished C-formyl alpha-l- and alpha-d-threofuranosides. The above
      C-glycosyl aldehydes were all prepared on a meaningful preparative scale starting
      from gram quantities of galactans. Finally, a new procedure for the preparation
      of the 2,3-O-benzyl l-threofuranose was established by Baeyer-Villiger oxidation
      of the benzylated C-formyl alpha-l-threofuranoside here prepared from agarose.

PMID- 19156326
TI  - Formation of N-heterocycles by the reaction of thiols with glyoxamides: exploring
      a connective Pummerer-type cyclisation.
AB  - The reaction of thiols with glyoxamides provides a convenient method for the
      generation of thionium ions and the initiation of Pummerer-type reactions. When
      the glyoxamides contain tethered aromatic nucleophiles, N-heterocycles are formed
      by a thionium ion cyclisation. The scope and mechanism of the connective Pummerer
      type process has been investigated using a range of thiols, Lewis acids and both
      mono- and bis-glyoxamides. The utility of the process has been illustrated in a
      synthesis of the indoloquinoline natural product, neocryptolepine.

PMID- 19156327
TI  - Inclusion complexes of cyclodextrins with nitroxide-based spin probes in aqueous
      solutions.
AB  - Formation of inclusion complexes between several cyclodextrin derivatives and
      TEMPO and DOXYL-based spin probes was studied by EPR spectroscopy. Competition
      between alkyl chains and nitroxide functionalities for cyclodextrin cavities
      leads to different types of complexation. Long alkyl chains in amphiphilic spin
      probes interact preferentially with cyclodextrins, and TEMPO units in such
      molecules are unaffected by complexation. DOXYL-type spin probes however form
      stronger complexes with cyclodextrins; this complexation changes hyperfine
      splitting and tumbling rate of the nitroxide group. Comparison of EPR spectra of
      free cyclodextrin and cyclodextrin-based polymeric nanocapsules made it possible
      to assess the tumbling of the spin probe inside the cyclodextrin units without
      the contribution of the tumbling of the whole complex.

PMID- 19156328
TI  - Tandem dispersion and killing of bacteria from a biofilm.
AB  - The combined effects of biofilm dispersion with a 2-aminoimidazole-triazole
      conjugate and bactericidal activity with a photodynamic inactivation agent
      suggest a novel combination therapy for treating diverse microbial infections.

PMID- 19156329
TI  - Identification and quantitation of vitamins K1 and K3 in cosmetic products for
      facial skin protection.
AB  - A simple and rapid analytical method was developed for the determination of
      vitamins K1 and K3 in facial anti-rash creams. The procedure is based on an
      ultrasonic extraction of the cosmetic sample with dimethylacetamide, in the
      presence of an internal standard, followed by HPLC separation. HPLC was performed
      using a C18 column and spectrophotometric detection at 333 nm. A linear gradient
      elution was carried out starting with 50% acetonitrile-methanol (75:25 v/v) and
      water up to 100% acetonitrile-methanol for 5 min. Linearity was established over
      the concentration range from 0.2 to 1.0 mg/ml for vitamin K1 and from 0.02 to 0.1
      mg/ml for vitamin K3, with LOD values of 100 ng and 20 ng injected, respectively.
      The accuracy was verified by spiking experiments on model cosmetic samples. The
      proposed method has been successfully applied for the analysis of commercial
      samples of creams.

PMID- 19156330
TI  - Determination and validation of six sunscreen agents in suncare products by UPLC
      and HPLC.
AB  - Methylene bis-benzotriazolyl tetramethyl butylphenol and bis-ethylhexyloxy phenol
      methoxyphenyl triazine are sunscreen agents that have hydrophobic behaviors in
      common. They were not normally assayed with the following four sunscreen agents
      that have hydrophilic behaviors in a single chromatographic run: ethylhexyl
      methoxycinnamate, isoamyl p-methoxycinnamate, ethylhexyl salicylate, and
      ethylhexyl triazone. For that reason, methylene bis-benzotriazolyl tetramethyl
      butylphenol and bis-ethylhexyloxy phenol methoxyphenyl triazine require much time
      in order to assay products with those materials. A rapid, selective, and
      reproducible determination method needs to be developed for the simultaneous
      examination of methylene bis-benzotriazolyl tetramethyl butylphenol and bis
      ethylhexyloxy phenol methoxyphenyl triazine with the sunscreen agents, ethylhexyl
      methoxycinnamate, isoamyl p-methoxycinnamate, ethylhexyl salicylate, and
      ethylhexyl triazone. This new technique could reduce time in examining the
      sunscreen agents and be effective for quality control of suncare products. In
      this paper, the HPLC and UPLC system is used for developing the determination of
      the sunscreen agents. Several evaluations of some mixtures of eluents and columns
      were obtained for the optimal condition of separation. In HPLC, the optimal peak
      resolution was obtained through ethanol-water gradient elution and a 75-mm C18
      column with a 3.5-microm-sized particle on a flow rate of 1.0 ml/min. In UPLC,
      the most distinctive peak resolution was obtained through methanol-water gradient
      elution and a 50-mm C18 column with a 1.7-microm-sized particle on a flow rate
      0.4 ml/min. Both of those chromatographic determination methods could be used in
      the examination of six types of sunscreen agents without any interference from
      other product excipients in the agents. The proposed determination methods were
      validated for specificity, linearity, repeatability, system stability,
      intermediate precision, and accuracy. Consequently, HPLC and UPLC determination
      methods could be rapid, selective, and proper applications for the assay of
      sunscreen agents in suncare products.

PMID- 19156331
TI  - Changes in hair properties by Eucalyptus extract.
AB  - A long-term usage investigation of a scalp lotion containing Eucalyptus extract,
      which increases the amount of ceramide in the skin, was carried out to explore
      the change in physical properties of the hair fiber. Half-head or whole-head
      usage studies of a scalp lotion with Eucalyptus extract were carried out for the
      following groups: Japanese female, Japanese senior female, Japanese male, and
      Caucasian female panelists. As a result, the improvement in hair luster and
      bounce in the root part of the hair were recognized by the panelists after the
      long-term application of the scalp lotion with Eucalyptus extract. Measurement of
      hair gloss intensity and bending stress at the root suggests that this
      improvement is based on changes in these physical properties. These results
      indicate that the recognition of panelists is based on an actual change in the
      hair fiber properties. The efficacy of Eucalyptus extract is expressed regardless
      of race, age, or gender, since similar results were confirmed in all panelist
      groups. In order to investigate the cause of these phenomena, we measured the
      elasticity (Young's modulus) of the new-growth part of the cortex in Eucalyptus
      extract-treated hair and placebo hair by the nano-indentation method of atomic
      force microscopy (AFM). These results suggest that the Young's modulus of the new
      growth part of the cortex in Eucalyptus extract treated-hair increases in
      comparison with placebo hair. The IR spectra of treated samples of hair show
      changes that appear to confirm a decrease in the alpha-helix structure and an
      increase in the beta-sheet structure.

PMID- 19156332
TI  - Polymer composite principles applied to hair styling gels.
AB  - A novel approach is taken to understand the mechanical performance of fixative
      treated hair tresses. Polymer composite principles are applied to explain the
      performance. Examples are given for polyacrylate-2 crosspolymer that show that
      the choice of neutralizer affects the film properties of anionic acrylic polymers
      by plasticization or by hardening through ionic (physical) crosslinking. The
      effect of these changes in the polymer film on the composite properties was
      determined by mechanical stiffness and high-humidity curl retention testing. It
      is shown that both adhesion to the hair and polymer cohesion are important in
      determining fixative polymer performance. The implications of the results for the
      formulation of fixative systems are discussed.

PMID- 19156333
TI  - DPPH free-radical scavenging ability, total phenolic content, and chemical
      composition analysis of forty-five kinds of essential oils.
AB  - Forty-five kinds of commonly used essential oils were employed to investigate the
      DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging ability and total
      phenolic content of major chemical compositions. The free-radical scavenging
      ability and total phenolic content of cinnamon leaf and clove bud essential oils
      are the best among these essential oils. One-half milliliter of cinnamon leaf and
      clove bud essential oils (10 mg/ml EtOH) are shown to be 96.74% and 96.12% of the
      DPPH (2.5 ml, 1.52x10(-4) M) free-radical scavenging ability, respectively. Their
      EC50 (effective concentrations) are 53 and 36 (microg/ml). One milligram per
      milliliter of cinnamon leaf, clove bud, and thyme red essential oils were shown
      to be 420, 480, and 270 (mg/g of GAE) of total phenolic content, respectively.
      Eugenol in cinnamon leaf and clove bud essential oils (82.87% and 82.32%,
      respectively) were analyzed by GC-MS. It is clear that the amounts of the phenol
      compounds in essential oils and the DPPH free-radical scavenging ability are in
      direct proportion.

PMID- 19156338
TI  - [Molecular aspects of lymph node metastasis].
AB  - The risk of local and systemic lymphatic metastasis of a tumor increases with the
      size of the malignant neoplasia. Lymph vessels are generated in the tumor and
      seem to follow anatomically defined pathways. However, the precise molecular and
      biological mechanisms seem to be complex and require definition. At present,
      molecules belonging to the vascular endothelial growth factors family and
      podoplanin have been identified as key for the proliferation of the tumor's
      lacteals. Molecular mechanisms of the tumor origin and the hematogenic and
      lymphatic dissemination are increasingly better defined by the use of new
      diagnostic and therapeutic approaches for tumor patients. Simultaneously, we
      might be able to influence processes such as cell growth, apoptosis,
      angiogenesis, and lymphogenic dissemination by novel drugs and thereby develop
      novel approaches for tumor treatment. Chemokine receptors seem to control
      essential steps of lymphogenic dissemination such as migration, invasion, and
      proliferation of tumor cells.

PMID- 19156339
TI  - [Andrological testosterone replacement therapy].
AB  - Male hypogonadism is characterised by decreased testicular function, especially
      testosterone deficiency. Its prevalence increases with age but may be acquired in
      all stages of life if it is not inborn. The lack of testosterone results in
      typical clinical symptoms. However, only about 10% of the affected men currently
      receive adequate treatment. A variety of testosterone preparations are available
      to meet the main needs of treatment, including intramuscular, transcutaneous,
      sublingual, and oral forms. In patients with prostate cancer, breast cancer,
      polycythemia, severe heart failure, obstruction of the lower urinary tract, or
      untreated sleep apnoea, testosterone treatment must be avoided. Therefore,
      clinical and laboratory screening are essential along with a long-term
      substitution.

PMID- 19156343
TI  - Degradation of fipronil (Termidor) in aqueous solution stored in polyethylene
      tanks exposed to sunlight or shade.
AB  - Pest Management Professionals commonly use polyethylene or fiberglass tanks for
      mixing and applying termiticides. We investigated the stability of fipronil
      (Termidor SC) (0.06%, 0.09% and 0.125% active ingredient) in aqueous solutions
      stored in polyethylene tanks under sun and shade for 2 week. Chemical analysis of
      tank-mixed solutions sampled at 0, 24, 48, 72, 168 and 336 h indicated that
      fipronil remained stable. Our data indicated that polyethylene tanks prevent
      fipronil from photodegradation and these tanks can be safely used for short term
      storage (up to 2 week) of liquid termiticides.

PMID- 19156344
TI  - Determining tissue-lead levels in large game mammals harvested with lead bullets:
      human health concerns.
AB  - Recently, the use of lead isotope ratios has definitively identified lead
      ammunition as a source of lead exposure for First Nations people, but the isotope
      ratios for lead pellets and bullets were indistinguishable. Thus, lead
      contaminated meat from game harvested with lead bullets may also be contributing
      to the lead body burden; however, few studies have determined if lead bullet
      fragments are present in big game carcasses. We found elevated tissue-lead
      concentrations (up to 5,726.0 microg/g ww) in liver (5/9) and muscle (6/7)
      samples of big game harvested with lead bullets and radiographic evidence of lead
      fragments. Thus, we would advise that the tissue surrounding the wound channel be
      removed and discarded, as this tissue may be contaminated by lead bullet
      fragments.

PMID- 19156345
TI  - A molecular biomarker for disruption of crustacean molting: the N-acetyl-beta
      glucosaminidase mRNA in the epidermis of the fiddler crab.
AB  - Several environmentally persistent chemicals have been found to be capable of
      disrupting crustacean molting. Considering the importance of molting in the life
      of crustaceans, there is a need to develop a molecular biomarker that can reflect
      the disrupting effects of contaminants on ecdysteroid signaling in crustaceans. N
      acetyl-beta-glucosaminidase (NAG) is a chitinolytic enzyme found in crustacean
      epidermis. The results of the present investigation show that the transcription
      of NAG gene in the epidermis of the fiddler crab, Uca pugilator, is inducible by
      the molting hormone 20-hydroxyecdysone, which validates the use of NAG mRNA as a
      biomarker for molt-disrupting effects of xenobiotics.

PMID- 19156346
TI  - Seasonal variation in organotins in the waters of the Dona Paula Bay, west coast
      of India.
AB  - Surface seawaters from the Dona Paula Bay, were collected at weekly intervals
      during March 2007 to March 2008, and analyzed for butyltins (BT) such as
      tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT) using a GC-MS system. The
      mean concentrations of TBT, DBT, MBT and total BT varied from <1-37, 4-19, 6-28
      and 21-84 ng Sn L(-1), respectively. Highest levels of BTs were recorded during
      May followed by April 2007 and March 2007 probably because the shipping and
      tourism activities are very high during these months.

PMID- 19156347
TI  - Levels and chiral signatures of organochlorine pesticides in urban soils of
      Yinchuan, China.
AB  - In this study, residual level and enantiomeric composition of typical
      organochlorine pesticides (OCPs) were surveyed in urban soils of Yinchuan, China.
      The median levels of summation Sigma HCHs and summation Sigma DDTs were 0.852 and
      2.24 ng/g, respectively, which suggested little risk for ecological environment
      and human health in the study area. Both chiral alpha-HCH and o,p'-DDT displayed
      the non-racemic signatures in all samples. The isomer ratios of summation Sigma
      HCHs and summation Sigma DDTs combined with enantiomer fractions (EFs) of alpha
      HCH and o,p'-DDT, suggested that contamination source of HCHs derived from
      historical HCHs (including technical HCHs and Lindane) and that of DDTs
      originated from old source with the usage of mixed technical DDTs and dicofol.

PMID- 19156348
TI  - Antipsychotic use and the risk of hip/femur fracture: a population-based case
      control study.
AB  - This case-control study showed that current use of conventional antipsychotics,
      but not atypical antipsychotics, seems to be associated with an increased risk of
      a hip/femur fracture, possibly related to the pharmacological properties of
      conventional antipsychotics. Furthermore, no evidence for a dose effect was
      found. INTRODUCTION: The aim of this study was to assess the risk of hip/femur
      fracture associated with antipsychotic use, with particular reference to any
      difference in risk with conventional versus atypical antipsychotics, dose, and
      pharmacological properties. METHODS: A case-control study was conducted using
      data from the PHARMO Record Linkage System among individuals aged 18 years and
      older between 1991 and 2002. Cases had a record of a hip or femur fracture, while
      controls had no evidence of ever having sustained any fracture. RESULTS: Most
      cases were elderly (77.6% aged > or = 70 years). We found an increased risk for
      hip/femur fracture associated with the use of antipsychotic drugs. The risk for
      current users (OR(adj) 1.68 [1.43, 1.99]) was significantly greater than with
      past use (OR(adj) 1.33 [1.14, 1.56]; p = 0.036). Current use of conventional
      antipsychotics (OR(adj) 1.76 [1.48, 2.08]) but not atypical antipsychotics
      (OR(adj) 0.83 [0.42, 1.65]) was associated with an increased risk. We did not
      find evidence for a dose effect. CONCLUSION: The use of conventional, but not
      atypical antipsychotics, seems to be associated with an increased risk of
      hip/femur fracture, possibly related to the pharmacological properties of
      conventional antipsychotics. However, the numbers of atypical antipsychotic users
      were small, and therefore this observation needs further attention in other study
      populations.

PMID- 19156351
TI  - Complete nucleotide sequences of okra isolates of Cotton leaf curl Gezira virus
      and their associated DNA-beta from Niger.
AB  - Okra (Abelmoschus esculentus) is a major crop in Niger. In the fall of 2007, okra
      leaf curl disease was observed in Niger and the begomovirus and DNA-beta
      satellite were found associated with the disease. The complete nucleotide
      sequences of DNA-A (FJ469626 and FJ469627) and associated DNA-beta satellites
      (FJ469628 and FJ469629) were determined from two samples. This is the first
      report of molecular characterization of okra-infecting begomovirus and their
      associated DNA-beta from Niger. The begomovirus and DNA-beta have been identified
      as Cotton leaf curl Gezira virus and Cotton leaf curl Gezira betasatellite,
      respectively, which are reported to also infect okra in Egypt, Mali and Sudan.

PMID- 19156350
TI  - Toward and away from spiders: eye-movements in spider-fearful participants.
AB  - Highly fearful individuals show attentional biases toward threat. However, it is
      still unclear whether initial engagement of attention toward threat or
      difficulties to disengage from threat is the underlying mechanism. We used eye
      tracking to investigate how quickly fear-relevant pictures are identified and
      whether they distract from the allocation of attention toward neutral targets.
      Pairs of fear-relevant and neutral pictures were presented to 18 high and 16 low
      spider-fearful participants. They were instructed to either fixate on a target or
      to fixate on the opposite picture, while eye movements were monitored
      continuously. Overall, fear-relevant targets were fixated more quickly than
      neutral targets. Spider-fearful participants had longer latencies when they had
      to identify the fear-relevant but fixate the neutral picture. Thus, attentional
      allocation toward threat was not specifically enhanced in fearful participants.
      Instead, they had difficulties to disengage attention from fear-relevant
      information. This disengagement deficit could be a cause, a correlate, or the
      result of phobic fear.

PMID- 19156349
TI  - Integrated signaling in heterodimers and receptor mosaics of different types of
      GPCRs of the forebrain: relevance for schizophrenia.
AB  - Receptor-receptor interactions within receptor heterodimers and receptor mosaics
      formed by different types of GPCRs represent an important integrative mechanism
      for signaling in brain networks at the level of the plasma membrane. The
      malfunction of special heterodimers and receptor mosaics in the ventral striatum
      containing D(2) receptors and 5-HT(2A) receptors in cortical networks may
      contribute to disturbances of key pathways involving ventral striato-pallidal
      GABA neurons and mediodorsal thalamic prefrontal glutamate neurons that may lead
      to the development of schizophrenia. The ventral striatum transmits emotional
      information to the cerebral cortex through a D(2) regulated accumbal-ventral
      pallidal-mediodorsal-prefrontal circuit which is of special interest to
      schizophrenia in view of the reduced number of glutamate mediodorsal-prefrontal
      projections associated with this disease. This circuit is especially vulnerable
      to D(2) receptor activity in the nucleus accumbens, since it produces a reduction
      in the prefrontal glutamate drive from the mediodorsal nucleus. The following
      D(2) receptor containing heterodimers/receptor mosaics are of special interest to
      schizophrenia: A(2A)-D(2), mGluR5-D(2), CB(1)-D(2), NTS(1)-D(2) and D(2)-D(3) and
      are discussed in this review. They may have a differential distribution pattern
      in the local circuits of the ventral striato-pallidal GABA pathway, predominantly
      located extrasynaptically. Specifically, trimeric receptor mosaics consisting of
      A(2A)-D(2)-mGluR5 and CB(1)-D(2)-A(2A) may also exist in these local circuits and
      are discussed. The integration of receptor signaling within assembled
      heterodimers/receptor mosaics is brought about by agonists and allosteric
      modulators. These cause the intramembrane receptor-receptor interactions, via
      allosteric mechanisms, to produce conformational changes that pass over the
      receptor interfaces. Exogenous and endogenous cooperativity is discussed as well
      as the role of the cortical mGluR2-5-HT(2A) heterodimer/receptor mosaic in
      schizophrenia (Gonzalez-Maeso et al. 2008). Receptor-receptor interactions within
      receptor heterodimer/receptor mosaics of different receptors in the ventral
      striatum and cerebral cortex give novel strategies for treatment of schizophrenia
      involving, e.g., monotherapy with either A(2A), mGluR5, CB(1) or NTS(1) agonists
      or combined therapies with some of these agonists combined with D(2)-like
      antagonists that specifically target the ventral striatum. In addition, a
      combined targeting of receptor mosaics in the ventral striatum and in the
      cerebral cortex should also be considered.

PMID- 19156352
TI  - School performance of international adoptees better than expected from cognitive
      test results.
AB  - OBJECTIVE: To investigate school performance of international adoptees in
      relation to their cognitive competence. METHOD: From the population of all male
      Swedish residents born 1973-1976, registered in the census 1985 and with complete
      test scores from military conscription, the following study groups were
      identified: Korean adoptees (n = 320), non-Korean adoptees (n = 1,125), siblings
      (children born by adoptive parents, n = 190) and Swedish majority comparisons (n
      = 142,024). Global scores from intelligence tests at conscription were compared
      with grade points from the last compulsory school year (year 9). Linear and
      logistic regression was applied in statistical analyses. RESULTS: The mean grade
      points in theoretical subjects were lower in non-Korean adoptees than in the
      majority population, but when global test scores from military conscription were
      adjusted for, outcomes were significantly better, equal for physics, than in the
      majority population. The grade points of Korean adoptees were higher than in the
      majority population and the same held true after adjusting for global test
      scores. When SES was taken into account, the risk of poor school performance
      (only completed lower subject levels) increased in non-Korean adoptees compared
      to models only adjusted for age and sex. CONCLUSION: Male international adoptees
      generally perform better in school than expected by their cognitive competence. A
      cognitive evaluation is important in the assessment of adoptees with learning
      difficulties.

PMID- 19156353
TI  - Children and adolescents with congenital heart disease: assessment of behavioural
      and emotional problems.
AB  - OBJECTIVE: The objective of the study was to assess behavioural and emotional
      problems in children and adolescents with congenital cardiac disease. DESIGN:
      From the database of Paediatric Heart Section, Rikshospitalet University
      Hospital, Norway, 430 patients and their parents were included and received
      questionnaires of youth self-report and child behavior checklist. The response
      rate was 71.4%. RESULTS: Compared to their parents children with congenital heart
      disease reported more behavioural and emotional problems. Boys scored
      significantly higher than girls in total problem score and externalising scores
      with more social problems, attention problems, delinquent behaviour and
      aggressive behaviour. No gender difference was found regarding internalising
      problem score. Compared to healthy boys, no differences were found in total
      problem, externalising or internalising score. In girls lower values were found
      in patients than healthy children for total problem, externalising and
      internalising scores. CONCLUSIONS: In the present study boys scored themselves
      higher with regard to total problem score than girls. No effect was found of due
      to different diagnoses. The data indicate that the children experience more
      problems than the parents are aware of. However, the behaviour problem scores in
      children with cardiac disease are significantly lower than in healthy children. A
      close parental follow-up and an experience of being exposed to life-threatening
      situation may play a role for the latter results.

PMID- 19156354
TI  - Polytraumatization and psychological symptoms in children and adolescents.
AB  - Previous research on the impact of traumatic experiences in children and
      adolescents has focused almost entirely on the effect of single trauma. Research
      on cumulative traumas has been lacking, but Finkelhor (Child Abuse Negl 31:7-26,
      2007) has recently directed the attention to the concept of polyvictimization. As
      an extension of this concept, this study examined the impact of
      polytraumatization, operationalized as the number of different potentially
      traumatic events. The study population comprised two cross-sectional samples of
      school-aged children (n = 270) and adolescents (n = 400). Information of life
      time incidence of traumatic events was collected by the life incidence of
      traumatic events (LITE), and psychological symptoms by the parent version of the
      strengths and difficulties questionnaire (SDQ) for the school children and the
      self-report trauma symptom checklist for children (TSCC) for the adolescents. We
      found that exposure to at least one traumatic event was common in both the
      samples (63% of the children and 89.5% of the adolescents). The number of
      different traumatic events, polytraumatization, was highly predictive of symptoms
      in both samples, and with a few exceptions surpassed the impact of specific
      events in exploratory analyses. We furthermore replicated previous findings of
      the important impact of interpersonal over non-interpersonal events on symptoms
      in both samples, and found an indication that this effect differed by gender in
      different manners in the two samples. This study emphasizes the significance of
      both the quantity of traumatic events, polytraumatization, as well as the
      quality, interpersonal events.

PMID- 19156355
TI  - Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment
      of attention deficit/hyperactivity disorder: a randomized, double-blind, placebo
      controlled study in stimulant-naive Swedish children and adolescents.
AB  - OBJECTIVE: The primary objective of this study was to assess the impact of
      atomoxetine in combination with psychoeducation, compared with placebo and
      psychoeducation, on health-related quality of life (HRQL) in Swedish stimulant
      naive pediatric patients with attention deficit/hyperactivity disorder (ADHD).
      HRQL results will be presented elsewhere. Here, psychoeducation as well as
      efficacy and safety of the treatment are described. PATIENTS AND METHODS: A total
      of 99 pediatric ADHD patients were randomized to a 10-week double-blind treatment
      with atomoxetine (49 patients) or placebo (50 patients). Parents of all patients
      received four sessions of psychoeducation. Atomoxetine was dosed up to
      approximately 1.2 mg/kg day (< or = 70 kg) or 80 mg/day (> 70 kg). Improvement of
      ADHD symptoms was evaluated using the ADHD rating scale (ADHD-RS) and clinical
      global impression (CGI) rating scales. Safety was assessed based on adverse
      events (AEs). RESULTS: The study population was predominantly male (80.8%) and
      diagnosed with the combined ADHD subtype (77.8%). The least square mean (lsmean)
      change from baseline to endpoint in total ADHD-RS score was -19.0 for atomoxetine
      patients and -6.3 for placebo patients, resulting in an effect size (ES) of 1.3
      at endpoint. Treatment response (reduction in ADHD-RS score of > or = 25 or > or
      = 40%) was achieved in 71.4 or 63.3% of atomoxetine patients and 28.6 or 14.3% of
      placebo patients. The lsmean change from baseline to endpoint in CGI-Severity was
      -1.8 in the atomoxetine group compared with -0.3 in the placebo group. The
      difference between treatments in CGI-Improvement at endpoint was -1.4 in favor of
      atomoxetine. No serious AEs occurred. The safety profile of atomoxetine was in
      line with the current label. CONCLUSIONS: Atomoxetine combined with
      psychoeducation was superior to placebo and psychoeducation in ADHD core symptoms
      improvement. The large ES might be a result of including stimulant-naive patients
      only, but also may indicate a positive interaction between atomoxetine treatment
      and psychoeducation, possibly by increased compliance.

PMID- 19156356
TI  - Moderate clinical improvement with maintenance ECT in a 17-year-old boy with
      intractable catatonic schizophrenia.
AB  - The use of electro-convulsive therapy (ECT) in adolescents is controversial, and
      few studies have been conducted to assess its efficacy and safety in this
      population. We report the case of a 19-year-old boy who received two series of
      ECT, one at 15 and another at 16, for intractable catatonic schizophrenia. Since
      the age of 17, he has required treatment combining clozapine and maintenance ECT.
      The course showed a sustained moderate improvement. The treatment permitted the
      patient to regain some autonomy with moderate adverse effects. ECT remains an
      uncommon treatment in adolescents, and the current case supports the view that it
      should not be banned in young people.

PMID- 19156358
TI  - Comparison of light harvesting and resource allocation strategies between two
      rhizomatous herbaceous species inhabiting deciduous forests.
AB  - Light conditions on the floor of deciduous forests are determined by the leaf
      dynamics of canopy trees and gap formation. Such spatiotemporal variations of
      light availability should affect the resource partitioning strategies of
      understory herbs. Although rhizomatous species are common in understory,
      relationships between rhizome structure, vegetative growth, and sexual
      reproduction are unclear in terms of carbon allocation. We compared the
      photosynthetic characteristics and carbon translocation patterns in the under
      canopy and light-gap sites between two summer-green perennial species: Cardamine
      leucantha with an annual long rhizome, and Smilacina japonica with a perennial
      short rhizome system. Flowering of both species occurs in early summer under
      decreasing light availability. In the light-gap, C. leucantha maintained high
      photosynthetic activity due to continuous leaf production, resulting in higher
      seed production than in the under-canopy. In contrast, the photosynthetic rate of
      S. japonica, producing leaves simultaneously, decreased with time irrespective of
      light conditions, resulting in stable seed production in both sites. Although
      seasonally decreasing light availability commonly restricts carbon assimilation
      of understory herbs, the responses of resource partitioning to variations in
      light availability depend greatly on the belowground structure of individual
      species.

PMID- 19156357
TI  - Thermus thermophilus as biological model.
AB  - Thermus spp is one of the most wide spread genuses of thermophilic bacteria, with
      isolates found in natural as well as in man-made thermal environments. The high
      growth rates, cell yields of the cultures, and the constitutive expression of an
      impressively efficient natural competence apparatus, amongst other properties,
      make some strains of the genus excellent laboratory models to study the molecular
      basis of thermophilia. These properties, together with the fact that enzymes and
      protein complexes from extremophiles are easier to crystallize have led to the
      development of an ongoing structural biology program dedicated to T. thermophilus
      HB8, making this organism probably the best so far known from a protein structure
      point view. Furthermore, the availability of plasmids and up to four thermostable
      antibiotic selection markers allows its use in physiological studies as a model
      for ancient bacteria. Regarding biotechnological applications this genus
      continues to be a source of thermophilic enzymes of great biotechnological
      interest and, more recently, a tool for the over-expression of thermophilic
      enzymes or for the selection of thermostable mutants from mesophilic proteins by
      directed evolution. In this article, we review the properties of this organism as
      biological model and its biotechnological applications.

PMID- 19156360
TI  - IgG stability in fresh and conditioned medium of tobacco (Nicotiana tabacum) and
      larch (Larix decidua) embryogenic suspension cultures.
AB  - To explore the feasibility of larch (Larix decidua Mill.) embryogenic cell
      culture as alternative plant expression system, protein stability in fresh and
      conditioned medium was characterized in this study and compared to tobacco BY2
      suspension culture. Fresh and conditioned media were spiked with 1 microg human
      IgG and IgG content was determined by ELISA after 24 h incubation. In fresh
      media, IgG recovery rate decreased to 12-23%. Adsorption on vessel walls probably
      is the best explanation for this IgG loss and EDTA in the medium strongly
      influenced wall adsorption. A high IgG recovery rate occurred in all conditioned
      cell culture media (7 or 14 days after inoculation). Changes in the low molecular
      weight-constitution of conditioned medium, rather than co-secreted polymers, are
      responsible for IgG stability in the cell suspension cultures.

PMID- 19156359
TI  - Induced interleukin-8 expression in gliomas by tumor-associated macrophages.
AB  - The tumor microenvironment affects tumor initiation, progression, and metastasis.
      However, it is still not clear how stromal cells interact with the tumor cells.
      By using a cytokine array immunoblot assay, we showed that interleukin (IL)-8, IL
      6, and RANTES (regulated upon activation normal T-cell expressed and secreted)
      proteins were up-regulated in GBM8401 glioma cells after coculture with human THP
      1-derived macrophages. IL-8 is a chemokine with leukocyte chemotactic,
      tumorigenic, and proangiogenic properties. To evaluate the correlation of IL-8
      expression with tumor-associated macrophages and angiogenesis, 43 glioma
      specimens were studied. The results showed that the IL-8 mRNA expression and
      microvessel count in glioma surgical specimens correlated positively with the
      density of tumor-associated macrophages. We further showed that IL-8 mRNA
      expression in GBM8401 cells increased dramatically, by 2(8)-2(10)-fold, after
      being cocultured with macrophages. This increase could also be induced by
      macrophage-conditioned medium, tumor necrosis factor-alpha, IL-1alpha, and IL
      1beta, and could be suppressed by anti-inflammatory agents including pyrrolidine
      dithiocarbamate, pentoxifylline, or dexamethasone. These findings imply that
      macrophage infiltration may be the common feature shared by cancer and
      inflammation, and macrophages could play a role in promoting glioma growth and
      angiogenesis by inducing IL-8 expression in glioma cells via inflammatory stimuli
      or the nuclear factor kappa B pathway.

PMID- 19156362
TI  - Identification and purification of metalloprotease from dry grass pea (Lathyrus
      sativus L.) seeds.
AB  - Proteolytic enzymes play a central role in the biochemical mechanism of
      germination. The present study reported the presence of Zn(2+)-dependent
      endoproteases in the dry seeds of grass pea (Lathyrus sativus L.) with maximum
      caseinolytic activity observed at pH 8.0. Studies with class-specific inhibitors
      (specific for cysteine, serine, aspartate, and metalloproteases) on crude extract
      identified the inhibitory effect of 1,10-phenanthroline. This inhibitory effect
      was overcome by addition of Zn(2+), not with Fe, Ca, Cu, Mg, or Co and indicates
      that the protease is Zn(2+) dependent. This metalloprotease was further
      characterized by attempting gelatin-PAGE zymography and observed three distinct
      zones of proteolytic activity with higher mobility. The protease fraction
      consisted of three isoforms as evidenced by the appearance of three different
      bands on gelatin-PAGE zymogram. We also purified these proteases to 110-fold by a
      three-step procedure comprising crude extract from dry seeds, (NH(4))(2)SO(4)
      fractionation, and casein-alginate affinity chromatography. The molecular mass of
      isoforms of metalloproteases is 25, 18, and 14 kDa.

PMID- 19156361
TI  - In silico construction of a protein interaction landscape for nucleotide excision
      repair.
AB  - To obtain a systems-level perspective on the topological and functional
      relationships among proteins contributing to nucleotide excision repair (NER) in
      Saccharomyces cerevisiae, we built two models to analyze protein-protein physical
      interactions. A recursive computational model based on set theory systematically
      computed overlaps among protein interaction neighborhoods. A statistical model
      scored computation results to detect significant overlaps which exposed protein
      modules and hubs concurrently. We used these protein entities to guide the
      construction of a multi-resolution landscape which showed relationships among
      NER, transcription, DNA replication, chromatin remodeling, and cell cycle
      regulation. Literature curation was used to support the biological significance
      of identified modules and hubs. The NER landscape revealed a hierarchical
      topology and a recurrent pattern of kernel modules coupling a variety of proteins
      in structures that provide diverse functions. Our analysis offers a computational
      framework that can be applied to construct landscapes for other biological
      processes.

PMID- 19156363
TI  - Exploring the C-H...O interactions in glycoproteins.
AB  - Glycoproteins are an important class of proteins that play a significant role in
      many cellular events. In the present study, we analyze the influence of C-H...O
      interactions in relation to other environmental preferences in glycoproteins.
      CH...O interactions are now accepted as a genuine hydrogen bond. Main chain-main
      chain interactions are predominant. Proline residues stabilize strands by C-H...O
      interactions in glycoproteins. Majority of the C-H...O interacting residues were
      conserved and had one or more stabilization centers. CH...O interactions might be
      responsible for the global conformational stability, since long-range CH...O
      contacts were predominant. The results presented in this study might be useful
      for structural stability studies in glycoproteins.

PMID- 19156364
TI  - Characterization of a newly isolated biphenyl-degrading bacterium, Dyella
      ginsengisoli LA-4.
AB  - A novel biphenyl-degrading bacterium, Dyella ginsengisoli LA-4 was isolated from
      activated sludge. This isolate could utilize biphenyl as sole source of carbon
      and energy. The resting cells of strain LA-4 could utilize 100 mg/L biphenyl
      within 20 h, and they were able to degrade 500 mg/L biphenyl within 40 h. The
      surfactant, Tween 80, could accelerate the biodegradation process. The increase
      of NaCl concentration inhibited the biphenyl degradation. No biphenyl degradation
      was detected when the NaCl concentration exceeds 10%. The effects of metal ions
      on biphenyl degradation were investigated. The results indicated that metal ions
      such as Cu(2+), Mn(2+), and Co(2+) could completely inhibit the biodegradation of
      biphenyl, but Mg(2+), Ca(2+), and Zn(2+) had no effects on the degradation of
      biphenyl. The removal rate was about 64% and 37% in the presence of Fe(3+) and
      Ni(2+), respectively. This study suggested that strain LA-4 could be widely used
      for bioremediation of soil and wastewater contaminated by biphenyl, NaCl, and
      metal ions.

PMID- 19156365
TI  - Thermophilic Bacillus coagulans requires less cellulases for simultaneous
      saccharification and fermentation of cellulose to products than mesophilic
      microbial biocatalysts.
AB  - Ethanol production from lignocellulosic biomass depends on simultaneous
      saccharification of cellulose to glucose by fungal cellulases and fermentation of
      glucose to ethanol by microbial biocatalysts (SSF). The cost of cellulase enzymes
      represents a significant challenge for the commercial conversion of
      lignocellulosic biomass into renewable chemicals such as ethanol and monomers for
      plastics. The cellulase concentration for optimum SSF of crystalline cellulose
      with fungal enzymes and a moderate thermophile, Bacillus coagulans, was
      determined to be about 7.5 FPU g(-1) cellulose. This is about three times lower
      than the amount of cellulase required for SSF with Saccharomyces cerevisiae,
      Zymomonas mobilis, or Lactococcus lactis subsp. lactis whose growth and
      fermentation temperature optimum is significantly lower than that of the fungal
      cellulase activity. In addition, B. coagulans also converted about 80% of the
      theoretical yield of products from 40 g/L of crystalline cellulose in about 48 h
      of SSF with 10 FPU g(-1) cellulose while yeast, during the same period, only
      produced about 50% of the highest yield produced at end of 7 days of SSF. These
      results show that a match in the temperature optima for cellulase activity and
      fermentation is essential for decreasing the cost of cellulase in cellulosic
      ethanol production.

PMID- 19156366
TI  - Optimization of effect factors for mycelial growth and exopolysaccharide
      production by Schizophyllum commune.
AB  - This paper is concerned with the optimization of effect factors for mycelial
      growth and exopolysaccharide production by Schizophyllum commune by one-factor-at
      a-time and orthogonal methods. The one-factor-at-a-time method was adopted to
      investigate the effects of six different compounds (sodium
      carboxymethylcellulose, L: -glutamic acid, V(B1), naphthalene acetic acid, oleic
      acid, and Tween 80) on mycelial growth and exopolysaccharide production. Among
      these factors, oleic acid, V(B1) and Tween 80 were identified to be the most
      important factors. Subsequently, the concentration of oleic acid, V(B1) and Tween
      80 were optimized using the orthogonal matrix method. The effects of the factors
      on the mycelial growth of S. commune were in the order of oleic acid > V(B1) >
      Tween 80, and those on exopolysaccharide production were in the same order. The
      optimal concentration for mycelia and exopolysaccharide were determined as oleic
      acid 0.1% (v/v), V(B1) 0.5 mg/L, and Tween 80 6 mg/L. The subsequent verification
      experiments confirmed the validity of the models. Under this optimized conditions
      in shake flask culture, the mycelial yield and exo-biopolymer production were
      25.93 and 2.79 g/L, respectively, which were considerably higher than those
      obtained in the preliminary studies. The result was further confirmed in a 7-L
      fermentor experiments.

PMID- 19156367
TI  - Biodegradation of mixed phenolic compounds under high salt conditions and
      salinity fluctuations by Arthrobacter sp. W1.
AB  - High salt concentration and salinity fluctuations in wastewater challenge the
      efficiency of microbial strains used for cleanup of pollutants. In this study, it
      was investigated that the new isolated Arthrobacter sp. W1 degraded mixed
      phenolic compounds under complex salt conditions. The results showed that
      Arthrobacter sp. W1 was able to utilize various phenolic compounds as carbon
      source under high salt conditions. It can degrade phenol and p-cresol mixture at
      10% NaCl, although rates of degradation and cell growth were lower compared to 5%
      NaCl. The presence of trace p-cresol significantly inhibited phenol
      biodegradation. When salinity fluctuations were between 1% and 10% NaCl, strain
      W1 was able to degrade substrates and survived. It was also suggested that the
      presence of salts (i.e., NaCl, KCl, Na(2)SO(4), and K(2)SO(4)) had almost no
      effects on the microbial growth and biodegradation process. Therefore,
      Arthrobacter sp. W1 would be a promising candidate for bioremediation of phenolic
      compounds under complex salt conditions.

PMID- 19156368
TI  - Efficient 1,3-propanediol production by fed-batch culture of Klebsiella
      Pneumoniae: the role of pH fluctuation.
AB  - The fermentative production of 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae
      under different fed-batch strategies was investigated. pH-stat fed-batch
      strategies proved to be not effective for economical 1,3-PD production for the
      existence of relatively high concentration of byproducts and residual glycerol at
      the end of the fermentation. However, in the pH-stat fed-batch strategy, an
      important phenomenon was observed that the yields of two main byproducts, 2,3
      butanediol and lactic acid, were closely related to pH value. The dominant
      byproduct was 2,3-butanediol at a pH value of 5.0 to 6.5 but changed to be lactic
      acid at a pH value of 7.1 to 8.0. Based on the analysis of the phenomenon, a self
      protection mechanism in K. pneumoniae, namely that the growing K. pneumoniae
      cells switch the metabolic pathways responding to environmental pH changes, was
      proposed. Thus a kind of feeding strategy was further applied during which the pH
      value was fluctuated between 6.3 and 7.3 periodically by feeding glycerol-ammonia
      mixture and sulphuric acid to make the metabolic pathways of 2,3-butanediol and
      lactic acid sub-active under the periodical low or high pH stress. At last,
      efficient 1,3-PD production was fulfilled under this fed-batch strategy, and the
      best results were achieved leading to 70 g/l 1,3-PD with a yield of 0.70 mol/mol
      glycerol and productivity of 0.97 g/l/h, while the two main byproducts and
      residual glycerol were under low concentrations.

PMID- 19156369
TI  - Screening of oleaginous yeast strains tolerant to lignocellulose degradation
      compounds.
AB  - High cost of triacylglycerol lipid feedstock is the major barrier for commercial
      production of biodiesel. The fermentation of oleaginous yeasts for lipid
      production using lignocellulose biomass provides a practical option with high
      economic competitiveness. In this paper, the typical oleaginous yeast strains
      were screened under the pressure of lignocellulose degradation compounds for
      selection of the optimal strains tolerant to lignocellulose. The inhibitory
      effect of lignocellulose degradation products on the oleaginous yeast
      fermentation was carefully investigated. Preliminary screening was carried out in
      the minimum nutritious medium without adding any expensive complex ingredients
      then was carried out in the lignocellulosic hydrolysate pretreated by dilute
      sulfuric acid. Seven typical lignocellulose degradation products formed in
      various pretreatment and hydrolysis processing were selected as the model
      inhibitors, including three organic acids, two furan compounds, and two phenol
      derivatives. The inhibition of the degradation compounds on the cell growth and
      lipid productivity of the selected oleaginous yeasts were examined. Acetic acid,
      formic acid, furfural, and vanillin were found to be the strong inhibitors for
      the fermentation of oleaginous yeasts, while levulinic acid, 5
      hydroxymethylfurfural, and hydroxybenzaldehyde were relatively weak inhibitors.
      Trichosporon cutaneum 2.1374 was found to be the most adopted strain to the
      lignocellulose degradation compounds.

PMID- 19156370
TI  - Study on mass transfer of isopropylbenzene and oxygen in a two-phase partitioning
      bioreactor in the presence of silicone oil.
AB  - A two-phase partitioning bioreactor to treat gas effluents polluted by volatile
      organic compound has been developed. In this work, both the mass transfer of
      isopropylbenzene (IPB) and oxygen have been considered in relation to their
      influence on the hydrodynamics of the reactor and the type of silicone oils used
      as a second phase. The synergistic effect of silicone oil and stirrer speed on
      the global oxygen mass transfer coefficient (KLa) and gas holdup (up to 12%) have
      been investigated. The addition of 10% of low viscosity silicone oil (10 cSt) in
      the reactor does not significantly affect the oxygen transfer rate. The very high
      solubility of IPB in the silicone oil leads to an enhancement of driving force
      term, especially for high fraction of silicone oil. However, it does not seem
      useful to exceed a volume fraction of 10% since KLa(IPB) decreases sharply at
      higher proportions of silicone oil. KLa(IPB) and KLaO2 evolve in the same way
      with the proportion of silicone oil. These results confirm the potentialities of
      our bioreactor to improve both the oxygen and pollutant gas transfer in the field
      of the treatment of gaseous pollutants, even for highly concentrated effluents.

PMID- 19156371
TI  - Biosorption of lead, copper, and cadmium by Phanerochaete chrysosporium in
      ternary metal mixtures: statistical analysis of individual and interaction
      effects.
AB  - Biosorption of three divalent metals, viz., lead, copper, and cadmium in ternary
      aqueous mixtures was studied using Phanerochaete chrysosporium in batch shake
      flasks. The mixtures were prepared containing the metals at their either varying
      optimum or equal initial concentration combinations in aqueous solution of pH
      optimum to each of the metals. Following were the optimum initial concentration
      ranges of the metals in mixture: lead, 60-100 mg/L; copper, 20-60 mg/L; and
      cadmium, 5-15 mg/L. And, for varying these optimum concentration levels of the
      metals, a 2(3) full factorial design of experiments was employed. The results
      revealed that an increase in lead and cadmium concentrations helped in their
      better biosorption by the fungus, but an increase in initial copper concentration
      slightly diminished its removal. Statistical analysis of the results in the form
      of analysis of variance and Student t test gave a clear interpretation on the
      roles of both the individual metals and their interactions in the uptake of
      metals from mixture. Compared to the uptake of metals when presented
      individually, lead biosorption in mixture was found to be enhanced to a degree as
      high as 99%; on the other hand, copper and cadmium removals from mixtures were
      inhibited to the extent of 100% and 98%, respectively. However, this extent of
      inhibition or enhancement in the metal removals compared to the individual
      removals was less in mixtures containing all equal concentrations of the metals.

PMID- 19156372
TI  - Systematic review of efficacy of rFVIIa and aPCC treatment for hemophilia
      patients with inhibitors.
AB  - INTRODUCTION: The primary treatment for mild-to-moderate bleeding disorders in
      hemophilia is either recombinant activated factor VII (rFVIIa) or activated
      prothrombin complex concentrate (aPCC). The efficacy of both products has been
      evaluated in individual studies; however, there has not been an overall review to
      compare the efficacy from these individual studies of rFVIIa and aPCC. Our aim is
      to establish robust estimates of the efficacy, speed of bleed resolution, and
      adverse event profile of both rFVIIa and aPCC. METHODS: A systematic review was
      conducted of the relevant literature. RESULTS: We identified 11 open-label cohort
      studies, six randomized clinical trials, including two head-to-head clinical
      trials, and a meta-analysis. The definition of efficacy varies between these
      studies, but is usually a composite measure of definite pain relief, reduction in
      the size of the hemorrhage, and cessation of bleeding. The individual making the
      interpretation of efficacy and the time from treatment initiation to recording
      the efficacy endpoint also varies across the studies. Overall, estimates of
      efficacy from randomized clinical trials using dosing regimens in line with the
      guidelines are higher for rFVIIa (81%-91%) than for aPCC (64%-80%). Conclusions
      from a meta-analysis suggest that treatment with rFVIIa may be associated with a
      faster time to joint bleed resolution than aPCC due to higher efficacy levels at
      different time points. The results from a comparative trial support the improved
      efficacy rates associated with rFVIIa compared with aPCC. CONCLUSION: The wide
      variations in definitions of efficacy and study methods make comparison of
      results across studies difficult. Further head-to-head trials should incorporate
      a standardized measurement for defining efficacy.

PMID- 19156373
TI  - [What is possible in outpatient care -- what is needed for inpatient care?].

PMID- 19156374
TI  - [Acute coronary syndrome - a challenge for the cooperation between outpatient and
      inpatient care].
AB  - Acute coronary syndrome (ACS) summarizes all phases of coronary heart disease,
      which are imminently life-threatening. In clinical practice, these are unstable
      angina pectoris, acute myocardial infarction, and sudden cardiac death. As the
      transitions between these clinical entities are smooth, it has been established
      during the last years to distinguish patients based on ECG findings in groups
      with (STEMI) and without ST segment elevation (NSTEMI/unstable angina pectoris).
      Because of the life-threatening character of this disease, continuous monitoring
      and immediate diagnostic evaluation are mandatory in all patients with suspected
      ACS. Regularly, this has to be done in the emergency department of a hospital. As
      the diagnostic and therapeutic management of ACS necessitates rapid decision
      making, an optimal cooperation between outpatient and inpatient departments is
      essential for maximal therapeutic performance. However, it has been shown that
      only 20-30% of patients admitted to an emergency department with acute chest pain
      have ACS and only 10-15% have acute myocardial infarction. About 50% of patients
      presenting with acute chest pain are part of a low-risk group and do not need
      hospital admission. On the other hand, 2-8% of patients with acute myocardial
      infarction are misdiagnosed in interdisciplinary emergency departments and
      discharged too early in spite of an ongoing life-threatening risk. Therefore,
      chest pain units (CPUs) were founded in many hospitals to optimize the diagnosis
      and treatment of ACS and the related consumption of financial resources. A task
      force of the German Society of Cardiology is presently preparing a consensus
      paper on the basic requirements for CPUs in Germany. The positioning of CPUs at
      the gateway between outpatient and inpatient care and the additional need for
      short-term outpatient exercise testing (stress ECG, stress echocardiography,
      scintigraphy, stress MRI) after ruling out ACS and myocardial infarction,
      predestine these facilities for new models of managed care including
      cardiologists in private practice.

PMID- 19156375
TI  - [Catheter ablation for atrial fibrillation: clinically established or still an
      experimental method?].
AB  - Interventional treatment for atrial fibrillation (AF) has been introduced as a
      therapeutic option soon after the pulmonary veins (PV) have been discovered as
      the dominant sources of paroxysmal atrial fibrillation (PAF). Elimination of PV
      conduction is the initial goal during catheter ablation in this setting. The
      success rate after the initial procedure varies between 60% and 85%, with > 80%
      after subsequent interventions. Supported by the current guidelines,
      interventional treatment of AF is indicated in case of symptomatic arrhythmias
      refractory to antiarrhythmic treatment. The introduction of the combined,
      stepwise approach has been another important breakthrough with regard to the
      treatment of chronic persistent atrial fibrillation (CAF). This strategy includes
      the combination of all conventional ablation strategies (pulmonary vein isolation
      [PVI], defragmentation, linear ablation) with the goal of AF termination by
      radiofrequency current. The first procedure for CAF treatment is quite frequently
      also only the first step toward stable sinus rhythm with a favorable outcome
      after AF termination (> 80% sinus rhythm). In more than half of the patients
      predominantly atrial arrhythmias other than AF have to be targeted in a second
      procedure. This approach is currently under clinical investigation and so far not
      "clinically established" due to the fact that it is a quite time-consuming and
      challenging procedure even in experienced centers. Future studies may help to
      identify predictors for procedure failure (e.g., left atrial size, AF duration,
      atrial cycle length) in order to improve patient selection. Additionally, it has
      to be underscored, that in PAF the relatively high recurrence rate after the
      first procedure still is the subject of further investigations. This aspect might
      be improved by the introduction of novel strategies (i.e., testing of concealed
      PV conduction after ablation with adenosine) or technologies (i.e., robotic
      navigation) for PAF ablation.

PMID- 19156376
TI  - [Diagnostics of patients with syncope of unknown origin: indications for hospital
      admission and for in- and out-hospital services?].
AB  - The diagnostic challenge of patients with syncope is to assess the underlying
      cause leading to the symptom syncope. In addition, the patient's risk for an
      increased mortality and for recurrent syncope has to be evaluated. Initial
      evaluation identifies most of these patients. Depending on the local medical
      health services this can be performed in an emergency department, an in- and out
      hospital service or at a general practitioner. Major criteria for hospital
      admission are risk stratification especially for patients with a suspected rhythm
      related reason for syncope and treatments to prevent syncopal recurrences.
      Hospital admission is not necessary for patients with a single attack or
      infrequent episodes who show no evidence of a cardiac cause for the syncope or of
      a structural heart disease. Patients who have no findings indicating the presence
      of life-threatening rhythm disorders can be further evaluated in a hospital or an
      out-clinic setting depending on the predetermined requirements of local
      professional bodies.

PMID- 19156377
TI  - [Latest proceedings: remote medicine - ready for clinical practice?!].
AB  - Changes in the demographic structure, increasing multimorbidity in connection
      with a rise in the number of chronic illnesses and the absence of an effective
      coordination of the different levels of healthcare services with its
      discontinuous processes and redundancies will increase the economic burdens in
      the German health-care system. Recent developments and appropriate logistic
      premises nowadays offer a realistic basis for implementing remote medicine as a
      central service and information tool as well as an instrument controlling the
      information and data flow between patient, hospital and medical practitioner.
      This article highlights current and future strategies including diagnostic and
      therapeutic options. The focus will concentrate on patients with heart rhythm
      disturbances, advanced congestive heart failure, and patients with implantable
      devices, i.e., pacemaker and implantable cardioverter defibrillator (ICD).

PMID- 19156378
TI  - [Rehabilitation 2008: when to use outpatient and inpatient rehabilitation?].
AB  - Due to illnesses of the cardiovascular system, costs of approximately 35 billion
      Euros arise in Germany per annum. This corresponds to around 15% of all costs
      arising in public-health service. Because of a positive influence of high-risk
      factors, high-risk illnesses, training condition, and lifestyle it is possible to
      improve the prognosis of the concerned patient within the scope of a training
      based cardiac rehabilitation program. Altogether, the final costs of each case
      will be lowered by a cardiac rehabilitation. A proven advantage of an inpatient
      rehabilitation program over an outpatient rehabilitation program is not given. As
      the costs of outpatient measures are less than the costs of inpatient
      rehabilitation, outpatient measures usually should be preferred. Inpatient
      rehabilitation should only be carried out with patients who cannot take part in
      outpatient cardiac rehabilitation programs on account of attendant circumstances
      (e.g., age, comorbidities, immobility). As there is no adequate overall medical
      care with outpatient rehabilitation centers in Germany, around 90% of all cardiac
      rehabilitations usually takes place under inpatient conditions far away from
      home. In almost every case, however, the realization of close-to-home
      rehabilitation is to the best advantage. Regardless whether this is realized on
      an inpatient or outpatient basis, close-to-home rehabilitation also allows the
      social environment of the patient to be included into the care. Due to being
      close to home, also long term-based and everyday-attendant rehabilitation types
      would be possible in future.

PMID- 19156379
TI  - [Comparative cost analysis of outpatient and inpatient rehabilitation for cardiac
      diseases].
AB  - PURPOSE: : To examine costs of inpatient and outpatient rehabilitation for
      cardiac disorders from the perspective of a major statutory health insurance fund
      in Germany. METHODS: : A nationwide database from a major health insurance fund
      in Germany was used to evaluate all rehabilitation cases in 2005. In addition to
      all direct cost domains of the rehabilitation itself, costs incurred in the
      preceding and the following year for hospital treatment, drugs and physical
      therapy were analyzed. A cost-cost analysis in different institutional settings
      was chosen for the cost comparison of in- and outpatient rehabilitation. To
      minimize the influence of possible confounders, a statistical control system was
      implemented. RESULTS: : Mean costs were 2,006 Euros for inpatient rehabilitation
      and 1,502 Euros for outpatient rehabilitation. No systematic differences were
      identified between in- and outpatient rehabilitation in costs for drugs and
      physical therapy in the year preceding and the year directly following the
      rehabilitation. The costs for hospital treatment in the year before
      rehabilitation were higher in inpatient rehabilitation, whereas in the year after
      rehabilitation no differences between in- and outpatient rehabilitation were
      seen. CONCLUSION: : Assuming comparable medical outcome, outpatient
      rehabilitation seems to pose a superior alternative compared to inpatient
      rehabilitation from an economic perspective. Hence, from the perspective of the
      statutory health insurance, fostering a higher market share of outpatient
      rehabilitation may add to a better allocation of overall health-care resources.

PMID- 19156380
TI  - [Temporal trends in the use of drug-eluting stents in German clinical practice].
AB  - BACKGROUND AND PURPOSE: : Drug-eluting stents (DES) have been shown to reduce the
      risk of in-stent stenosis, one of the major problems of percutaneous coronary
      intervention (PCI) with implantation of baremetal stents. DES are approved in
      Germany since 2002. The following study is based on data of the ALKK PCI registry
      and assesses the use of DES depending on patient characteristics, indication and
      coronary status comparing the treatment years 2003 and 2005. METHODS: : The ALKK
      (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte) PCI registry is
      focused on quality management based on guidelines in coronary interventions. Data
      were obtained by standardized questionnaires and analyzed centrally at the KL
      Neuhaus Datenzentrum, Ludwigshafen, Germany. For this study, data of 40,434 PCI
      procedures of 32 hospitals were obtained. RESULTS: : In 2003, a total of 18,564
      PCIs, and in 2005, a total of 21,870 PCIs were registered. Figure 1 shows the
      rate of DES in PCI in the hospitals participating in the registry in both years,
      2003 and 2005. The use of DES was low with 4.3% in 2003 and increased to 19.1% in
      2005. DES were mostly used in patients with stable angina (2003: 68.4%, 2005:
      55.3%), in patients with former PCI (2003: 42.5%, 2005: 48.1%) and a positive
      stress test (DES 2003: 58.4%, 2005: 32.0%; Table 1). The rate of DES was high in
      unprotected left main procedures (DES 2003: 15.6%, 2005: 35.9%), PCI of ostial
      lesions (DES 2003: 6.4%, 2005: 32.7%), in in-stent stenosis (DES 2003: 9.5%,
      2005: 40.6%), and in multivessel PCI (DES 2003: 7.6%, 2005: 29.3%; Figure 3).
      CONCLUSION: : DES were mainly applied in a stable situation (Figure 2), but were
      also increasingly used for complex coronary interventions in off-label
      indications.

PMID- 19156381
TI  - Dizziness and near syncope due to sinus bradycardia and sinoatrial block
      associated with obesity and daytime tiredness. A clear indication for pacemaker
      implantation?
AB  - BACKGROUND: The symptomatic sick sinus syndrome presents a classic indication for
      the implantation of a dual-chamber pacemaker according to the current national
      and international guidelines. However, in cases where dizziness and near syncope
      due to a sinus node dysfunction are found together with clinical characteristics
      of a sleep apnea-hypopnea syndrome (SAHS), screening for sleep apnea would be
      prudent before deciding for a pacemaker. CASE STUDY: The case report presented
      herein describes a patient with symptomatic sinus bradycardia and second-degree
      SA block with a Wenckebach periodicity, in whom the primary decision to implant a
      pacemaker was altered in favor of treatment with nCPAP (nasal continuous positive
      airway pressure) because after a careful and thorough evaluation of the patient's
      history and symptoms, a severe mixed SAHS was diagnosed. CONCLUSION: On
      diagnosing SAHS with an obstructive component in patients with symptomatic
      bradycardia and SA block, there is no primary need for a pacemaker, but rather
      for implementing treatment with nCPAP. Thus, a pacemaker should only be
      considered in patients with intolerance or bad compliance regarding nCPAP, or in
      those in whom no significant reduction of bradyarrhythmia is achieved.

PMID- 19156386
TI  - Image of the month. Massive right atrial thrombus due to heparin-induced
      thrombocytopenia type II.

PMID- 19156387
TI  - [Breaking new ground in teaching medical students emergency medicine. Evaluation
      of a multi-centre student-guided teaching concept].
AB  - BACKGROUND: Medical students who want to apply for preliminary medical
      examinations in Germany have to prove that they have attended a first-aid course.
      However, lay courses are often not up to the standards and needs that medical
      students require. As a result since 1996 members of the task group "AGEHMED", all
      of whom are medical students, have been teaching their peers in target groups
      orientated first aid and emergency techniques at medical school. The task group
      is (currently) active with 190 students at 6 German medical schools. All
      students, even those without any previous knowledge, can participate in emergency
      medicine education of their peers following a supervised 5-step model. OBJECTIVE:
      The aim of this study was to examine the results of a questionnaire that was used
      for evaluation of peer-guided first-aid courses at medical schools over the last
      7 years and to assess its validity and reliability. MATERIALS AND METHODS: From
      2000 to 2007 59 first-aid courses with 4,941 medical students were evaluated.
      After carrying out descriptive analyses the factorial validity and reliability
      (Cronbach's alpha) of the questionnaire were assessed. The inter-scale
      correlation of the significant factors was also analysed. RESULTS: The courses
      were continuously well rated. The amount of variance explained by the
      factors"quality of the course","learning success","comparison to other university
      courses","overall satisfaction" and"scheduling of the course" was 68%. The mean
      inter-scale correlation was r=0.23 and Cronbach's alpha was between 0.62 and
      0.81. CONCLUSIONS: The peer-guided courses have been continually well received by
      the course participants over the last 7 years. The questionnaire shows sufficient
      validity and reliability. Based on these results, it can be presumed that this
      approach can be more widely put into practice in the education of medical
      students.

PMID- 19156389
TI  - [Intrahospital transport of critically ill patients].
AB  - Transport of critically ill patients from the ICU for diagnostic and therapeutic
      purposes (e.g. CT, endoscopy, radiological catheter-assisted interventions) is a
      challenge and has steadily increased over the years. After risk-benefit analysis
      careful planning is the first step in minimizing the risk of complications.
      Knowledge and skillful handling of the transport equipment is mandatory to avoid
      life-threatening incidents as monitoring and therapy have to be continued during
      the transport. Proper education and experience in critical care medicine are
      additional characteristics of the transport team. When these prerequisites are
      fulfilled a "non-transportable" patient is just as unlikely as a "non
      anesthetizable" patient.

PMID- 19156391
TI  - [Advance health care directives as seen by surgical patients].
AB  - BACKGROUND: Progressive health care implies progress also in physician/patient
      interaction, especially with regard to moribund patients and their relatives.
      Advance health care directives emerged from the desire to influence medical
      treatment even in borderline situations. In spite of the present political and
      public discussions in Germany, advance directives are rarely of much importance
      in everyday surgical practice. By means of questionnaires, this study aimed at
      the frequency of advance directives among the patients of a surgical hospital and
      at related influencing factors. METHODS: Between August 2007 and January 2008,
      450 patients at our hospital were interviewed, prior to scheduled surgery, on the
      topic of advance health care directives by means of anonymous questionnaires. In
      addition to questions about the existence of or the intention to draw up advance
      directives, the study focussed particularly on the relationship between patient
      and attending physician. Patient-specific and sociodemographic data were
      collected as well. RESULTS: Of the patients interviewed, 16.7% stated they had
      drawn up advance directives, while 21.3% did not know about the possibility of
      drawing up such a document. A mere 9.7% of the patients interviewed saw no need
      for such directives, whereas the majority (65.3%) considered it an option. Among
      the factors influencing the drawing up of advance directives, age and prior
      experience with severe disease figured significantly. Of the patients
      interviewed, 64.8% wished for more information on the topic of advance health
      care directives and health care proxies. The wish was expressed by 80.1% of
      patients that the attending surgeon mention the topic prior to surgery.
      CONCLUSIONS: Although the proportion of patients that draw up advance health care
      directives continues to be less than one fifth, surgical patients have a great
      need for information regarding the topic. Surgical hospital personnel should also
      set themselves to this task.

PMID- 19156390
TI  - [Opioid-induced immunosuppression. A clinically relevant problem?].
AB  - Several in vitro and animal studies have demonstrated the immunosuppressive
      effects of opioids and an increased risk of infection. The clinical relevance of
      these findings is unclear. In this review the relevant animal and human studies
      on the relationship of opioid use and risk of infection are summarized. The areas
      of retroviral infections (i.e. human immunodeficiency virus, HIV), sepsis and
      pneumonia, postoperative and chronic pain therapy are covered. In the majority of
      animal studies an increased risk of infection was demonstrated but in human
      studies these findings were contradictory. However, these studies were frequently
      underpowered because they involved small patient collectives and do not reflect
      the standards of evidence-based medicine. In summary, a causal relationship
      between opioid therapy and an increased risk of infection could neither be
      conclusively demonstrated nor fully excluded.

PMID- 19156392
TI  - [Multidisciplinary treatment for adult soft tissue sarcoma].
AB  - The current standard in local treatment of soft tissue sarcomas has shifted from
      amputation and similar mutilating resections to more organ- and function
      preserving surgery. This was possible through multidisciplinary treatment
      approaches, particularly those including adjuvant radiation therapy. Adjuvant
      radiation showed significant improvement in local tumour control after resection
      with tight margins and in high-risk sarcomas. Unfortunately adjuvant radiation
      failed to improve overall survival. Perioperative chemotherapies also have not
      contributed to improvement in the overall prognosis worldwide. Progress may occur
      when the pathogenesis and molecular profile of specific sarcoma subtypes are
      better understood, allowing more effective new drugs. One example is the
      treatment of advanced gastrointestinal stromal tumour with imatinib, a small
      molecular kinase inhibitor of the c-kit receptor. Presently the most effective
      measure to improve the prognosis with soft tissue sarcomas is early patient
      referral to expert centres, where diagnostic workup and therapy decisions are
      made on a multidisciplinary basis and updated according to the newest guidelines
      and study results.

PMID- 19156393
TI  - [Community-acquired pneumonia].
AB  - Community-acquired pneumonia is the most common cause of death amongst all
      infectious diseases in the world. Mortality is low in patients treated as
      outpatients (<1%), but significantly raised (close to 14% in Germany) in hospital
      admitted patients. Especially at risk are patients from nursing homes, and
      patients with co-morbidities (chronic heart failure, chronic liver disease,
      neurological disease). Appropriate initial antibiotic therapy is the key factor
      in influencing patient outcome. Today, a risk stratification approach is used for
      initiating antibiotic therapy. Low risk patients can be treated as outpatients
      with a narrow spectrum beta-lactam for 5 days. With an increasing number of risk
      factors hospital admittance is recommended and broader spectrum antibiotics
      providing additional cover for atypical pathogens are required. Influenza and
      pneumococcal vaccination are proven to reduce the number and the severity of CAP
      cases significantly. The recommendations of the Standige Impfkommission (Stiko)
      in Germany therefore warrant implementation in daily practice.

PMID- 19156394
TI  - [The role of radiation therapy in treatment of pancreatic cancer from the
      viewpoint of radio-oncologists].
AB  - Despite great efforts in the field of preclinical and clinical research,
      pancreatic cancer is still one of the most devastating cancer diagnoses and
      nearly always results in death. With neoadjuvant chemoradiotherapy higher R0
      resection rates can be achieved in pancreatic cancer and may even lead to a
      secondary resection in primarily inoperable tumors. Patients who experience a
      disease progression due to aggressive tumor biology can be spared the unnecessary
      morbidity of resection by neoadjuvant therapy. Even in the adjuvant situation the
      rates of local relapse can be significantly reduced by combined
      chemoradiotherapy. Through progress in radiation techniques the toxicity of
      combined chemoradiotherapy could be lowered. If symptoms of the metastasized
      disease are caused by localized solitary or more widespread tumor manifestation,
      chemoradiotherapy should be considered for a rapid symptom relief. The adjunct of
      various biologicals to chemoradiotherapy is a promising new way to improve the
      prognosis of pancreatic cancer. Results from initial trials to clarify this
      concept are expected soon. Despite all progress in radiation techniques and in
      systemic therapy of pancreatic cancer, psychooncological care and good nutrition
      is of especially high importance in the care of this group of patients.

PMID- 19156395
TI  - [Operative therapy of bladder carcinomas].

PMID- 19156396
TI  - Facial necrotizing fasciitis in an infant caused by a five toxin-secreting
      methicillin-susceptible Staphylococcus aureus.

PMID- 19156397
TI  - Recurrent malaise and oedema in a 35-year-old female.

PMID- 19156398
TI  - Hippocampus: a future target for sepsis treatment!

PMID- 19156399
TI  - Endotoxin-induced gene expression differences in the brain and effects of iNOS
      inhibition and norepinephrine.
AB  - PURPOSE: We studied gene expression differences in brain homogenate, hippocampus,
      somatosensory cortex and cerebellum of rats suffering from sepsis-associated
      delirium and analyzed the effects of norepinephrine and 1,400 W (specific
      inhibitor of the inducible nitric-oxide synthase). METHODS: We applied microarray
      screenings to rat brain homogenate 1, 3 and 4.5 h after lipopolysaccharide (LPS,
      5 mg/kg) or 0.9% NaCl treatment. Therapy groups were analyzed after 4.5 h.
      Validations and compartment specific investigations were carried out by real-time
      PCR. RESULTS: Most striking gene expression differences were seen 4.5 h after LPS
      administration, especially within the hippocampus (chemokines and endothelial
      cell-specific molecule 1). Norepinephrine resulted in a discrete chemokine up
      regulation, while 1,400 W had hardly any effect. CONCLUSION: Strongest gene
      regulations were found within the hippocampus. Norepinephrine showed a tendency
      of having a proinflammatory influence, while 1,400 W had no clear-cut effect onto
      the gene expression level.

PMID- 19156400
TI  - Lack of specificity of antibodies directed against human beta-adrenergic
      receptors.
AB  - The present study was designed to investigate if antibodies against beta
      adrenergic receptors (betaARs) can be used to determine expression of betaAR in
      human myocardium. Western blotting was performed to investigate the specificity
      of antibodies directed against beta(1)AR and beta(2)AR in human left ventricular
      tissue. A comparison was made between cardiac tissue from patients with
      idiopathic dilated cardiomyopathy and ischemic heart disease and nonfailing
      donors. The antibodies directed against beta(1)AR and beta(2)AR recognized
      several protein bands at different molecular weights. Moreover, both antibodies
      also recognized multiple proteins in Chinese hamster ovary cells expressing
      beta(1)AR, beta(2)AR, and even beta(3)AR. betaAR antibodies are not specific and
      are not suited to study expression of betaAR in human myocardium.

PMID- 19156401
TI  - Negative compatibility effect: the object-updating hypothesis revisited.
AB  - A prime even if backward masked can affect the reaction to a subsequently
      presented target. According to the object-updating hypothesis, negative CE (i.e.
      longer reactions in the compatible than incompatible trials) occurs due to the
      interaction between prime and a subsequent stimulus (usually a mask or flanker).
      Its crucial assumption is that only new elements of the mask can affect the
      response. As the masks are usually composed of figures that call for both
      possible responses, the masks' new element calls for a response opposite to that
      initialized by the prime. Here an experiment is described in which the prime and
      target were two arrowheads pointing to left or right. Two different flankers were
      composed from the two heads pointing to the opposite directions. In contrast to
      the OU hypothesis, NCEs were different for the two flankers. This finding
      contradicts the OU hypothesis.

PMID- 19156402
TI  - Increased pain from muscle fascia following eccentric exercise: animal and human
      findings.
AB  - Mechanisms and structures which are involved in eccentric exercise-induced
      delayed onset muscle soreness (DOMS) are not yet clarified. Tissue and site
      specificity may be important considerations in afferent sensitisation following
      eccentric exercise. This study investigated the nociceptive response to
      hypertonic sodium solution applied to fascial/epimysium tissue and mechanically
      sensitised sites in muscle by assessing (1) afferent recordings in animals and
      (2) psychophysical assessment in humans. Seventeen male rats underwent eccentric
      contraction of extensor digitorum longus muscle, while 11 rats served as an
      unexercised naive group. Two days post-exercise, group IV afferent fibre activity
      was recorded in response to superfusion of hypertonic Krebs solution on the
      mechanically sensitised muscle/epimysium site. Mechanical sensitisation was
      confirmed with significant increases in afferent response and decreases in
      threshold to mechanical stimulation in the eccentrically exercised rats compared
      to naive rats. There was no difference in afferent response magnitude to
      hypertonic Krebs solution between exercise and naive groups. In the human study,
      13 volunteers participated. After bilateral assessment of pressure pain
      thresholds (PPT) along the tibialis anterior muscles, eccentric exercise was
      performed to induce DOMS in m. tibialis anterior of one leg. Site of maximal
      mechanical sensitivity was identified 24 h later and injected with hypertonic
      saline at fascial and deep muscle levels. The corresponding site on the opposite
      unexercised leg served as a control. Fascial injection of the exercised muscle
      caused significantly higher pain intensity compared to all other injections.
      Response to deep muscle stimulation was not different between sides. This
      suggests that fascia rather than muscle tissue is important in DOMS associated
      sensitisation.

PMID- 19156403
TI  - Context effects in haptic perception of roughness.
AB  - The influence of temporal and spatial context during haptic roughness perception
      was investigated in two experiments. Subjects examined embossed dot patterns of
      varying average dot distance. A two-alternative forced-choice procedure was used
      to measure discrimination thresholds and biases. In Experiment 1, subjects had to
      discriminate between two stimuli that were presented simultaneously to adjacent
      fingers, after adaptation of one of these fingers. The results showed that
      adaptation to a rough surface decreased the perceived roughness of a surface
      subsequently scanned with the adapted finger, whereas adaptation to a smooth
      surface increased the perceived roughness (i.e. contrast after effect). In
      Experiment 2, subjects discriminated between subsequent test stimuli, while the
      adjacent finger was stimulated simultaneously. The results showed that perceived
      roughness of the test stimulus shifted towards the roughness of the adjacent
      stimulus (i.e. assimilation effect). These contextual effects are explained by
      structures of cortical receptive fields. Analogies with comparable effects in the
      visual system are discussed.

PMID- 19156404
TI  - Losartan inhibits monocytic adhesion induced by ADMA via downregulation of
      chemokine receptors in monocytes.
AB  - OBJECTIVE: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide
      synthase (NOS) inhibitor, can induce the adhesiveness of monocytes to vascular
      endothelium, and chemokines play an important role in this process. The present
      study was carried out to test whether the inhibitory effect of losartan on ADMA
      induced monocytic adhesion is mediated by chemokine receptors. METHODS: Human
      monocytoid cells (THP-1) were incubated with exogenous ADMA (30 microM) for 4 or
      24 h in the absence or presence of losartan. The monocytic adhesion, the levels
      of chemokines, and the expression of chemokine receptors were determined. The
      possible signal pathway was also explored. RESULTS: In cultured monocytes, ADMA
      (30 microM) markedly increased monocytic adhesion to endothelial cells, elevated
      the levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL
      8), and upregulated the mRNA expression of chemokine receptors CCR2 and CXCR2.
      Exposure to ADMA (30 microM) significantly induced the generation of
      intracellular reactive oxygen species (ROS) and activation of nuclear factor (NF)
      kappaB. Pretreatment with AT1 receptor blocker (ARB) losartan (1, 3, 10 microM)
      attenuated monocytic adhesiveness elicited by ADMA and downregulated the
      expression of CCR2 and CXCR2 mRNA, accompanied by a significant decrease in ROS
      generation and NF-kappaB activity and expression. CONCLUSION: The present study
      suggests that the inhibitory effect of losartan on ADMA-induced monocytic
      adhesion may be related to downregulation of chemokine receptors by inhibiting
      the ROS/NF-kappaB pathway.

PMID- 19156405
TI  - MRI pattern of infarcts in basal ganglia region in patients with tuberculous
      meningitis.
AB  - INTRODUCTION: This study aimed to evaluate the pattern of infarct in basal
      ganglia region in tuberculous meningitis (TBM) and ischemic strokes and its
      sensitivity and specificity in the diagnosis of these disorders. METHODS:
      Patients with TBM and ischemic strokes in basal ganglia region were
      retrospectively evaluated from our tuberculous meningitis and ischemic stroke
      registry. Magnetic resonance imaging findings were grouped into anterior
      (caudate, genu, anterior limb of internal capsule, anteromedial thalamus) and
      posterior (lentiform nuclei, posterior limb of internal capsule, posterolateral
      thalamus). The sensitivity and specificity of these patterns in diagnosing TBM
      and ischemic stroke were evaluated. RESULTS: There were 24 patients in each
      group. Infarct in TBM was purely anterior in eight patients and in ischemic
      stroke purely posterior in 18 patients. The frequency of caudate infarct was
      significantly higher in TBM compared to ischemic stroke (37.5% vs 8.3%). In TBM
      patients, purely posterior infarcts were present in seven patients; three had
      associated risk factors of ischemic stroke. The sensitivity of pure anterior
      infarct in the diagnosis of TBM was 33%, specificity 91.66%. For ischemic stroke,
      the sensitivity of posterior infarct was 75% and specificity 70.83%. CONCLUSION:
      TBM patients having infarcts in posterior region should be looked for associated
      risk factors of ischemic stroke.

PMID- 19156406
TI  - Purification and characterization of a beta-1,4-glucosidase from a newly isolated
      strain of Fomitopsis pinicola.
AB  - An efficient beta-1,4-glucosidase (BGL) producing strain, Fomitopsis pinicola
      KMJ812, was isolated and identified based on morphological features and sequence
      analysis of internal transcribed spacer rDNA. An extracellular BGL was purified
      to homogeneity by sequential chromatography of F. pinicola culture supernatants
      on a DEAE-sepharose column, a gel filtration column, and then on a Mono Q column
      with fast protein liquid chromatography. The relative molecular weight of F.
      pinicola BGL was determined to be 105 kDa by sodium dodecylsulfate-polyacrylamide
      gel electrophoresis, or 110 kDa by size exclusion chromatography, indicating that
      the enzyme is a monomer. The hydrolytic activity of the BGL had a pH optimum of
      4.5 and a temperature optimum of 50 degrees C. The enzyme showed high substrate
      specificity and high catalytic efficiency (kcat=2,990 s-1, Km=1.76mM,
      kcat/Km=1,700 mM-1 s-1) for p-nitrophenyl-beta-d-glucopyranoside. Its internal
      amino acid sequences showed a significant homology with hydrolases from glycoside
      hydrolase family 3, indicating that the F. pinicola BGL is a member of glycoside
      hydrolase family 3. Although BGLs have been purified and characterized from
      several other sources, F. pinicola BGL is distinguished from other BGLs by its
      high catalytic efficiency and strict substrate specificity.

PMID- 19156407
TI  - Discovery of a pimaricin analog JBIR-13, from Streptomyces bicolor NBRC 12746 as
      predicted by sequence analysis of type I polyketide synthase gene.
AB  - Sequence analysis of ketosynthase domain amplicons from Streptomyces bicolor NBRC
      12746(T) revealed the presence of previously unreported type I polyketide
      synthases (PKS-I) genes. The clustering of these genes with the reference PKS-1
      sequences suggested the possibility to produce a polyene compound similar to
      pimaricin. Thus, the cultured sample from NBRC 12746(T) was analyzed for the
      production of polyene compounds. The strain produced an antifungal compound which
      displayed the UV absorption spectrum of tetraene macrolides. The structure
      determination based on the spectroscopic analysis of the purified compound
      resulted in the identification of a novel pimaricin analog JBIR-13 (1). This
      study therefore strongly suggested that a careful analysis of PKS-I genes can
      provide valuable information in the search of novel bioactive compounds within a
      class predicted from phylogenetic analysis.

PMID- 19156408
TI  - Functional neuroimaging in Hashimoto's encephalitis: a physiopathological
      imaging?

PMID- 19156409
TI  - Diagnostic accuracy of contrast-enhanced FDG-PET/CT in primary staging of
      cutaneous malignant melanoma.
AB  - PURPOSE: To evaluate the diagnostic accuracy of contrast-enhanced FDG-PET/CT (ce
      PET/CT), PET-only, and CT-only in patients with newly diagnosed and resected
      cutaneous malignant melanoma. METHODS: A final group of 56 patients (mean age 62
      years, range 23-86 years; 29 women, 27 men) were staged with ce-PET/CT after
      resection of the primary tumour. Histopathology as well as clinical follow-up
      (mean 780 days, range 102-1,390 days) served as the standards of reference.
      Differences between the staging modalities were tested for statistical
      significance with McNemar's test. RESULTS: All imaging procedures provided low
      sensitivities in the detection of lymph nodes (sensitivity N-stage: PET/CT and
      PET-only 38.5%; CT-only 23.1%) and distant metastases (sensitivity M-stage:
      PET/CT 41.7%, PET-only 33.3%, CT-only 25.0%) in initial staging after resection
      of the primary tumour. No statistically significant differences were detected
      between the imaging procedures (p > 0.05). PET/CT resulted in an alteration in
      further treatment in two patients compared to PET-only and in four patients
      compared to CT-only. CONCLUSION: All imaging modalities had a low sensitivity on
      initial staging of patients with malignant melanoma. Thus, close patient follow
      up must be considered mandatory.

PMID- 19156410
TI  - Chronic thyroiditis in patients with advanced breast carcinoma: metabolic and
      morphologic changes on PET-CT.
AB  - PURPOSE: To investigate clinical implications of FDG uptake in the thyroid glands
      in patients with advanced breast carcinoma by comparing metabolic and morphologic
      patterns on positron emission tomography (PET)/computed tomography (CT). METHODS:
      The institutional review board waived the requirement for informed consent. A
      retrospective analysis was performed in 146 women (mean age 54 years) with
      advanced breast carcinoma who received systemic treatment. All patients underwent
      PET-CT before and after treatment. All PET-CT studies were reviewed in consensus
      by two reviewers. Morphologic changes including volume and mean parenchymal
      density of the thyroid glands were evaluated. Maximum standardized uptake value
      (SUVmax) and total lesion glycolysis (TLG) were determined to evaluate metabolic
      changes. These parameters were compared between patients with chronic thyroiditis
      who received thyroid hormone replacement therapy and those who did not. RESULTS:
      Of the 146 patients, 29 (20%) showed bilaterally diffuse uptake in the thyroid
      glands on the baseline PET-CT scan. The SUVmax showed a linear relationship with
      volume (r = 0.428, p = 0.021) and the mean parenchymal density (r = -0.385, p =
      0.039) of the thyroid glands. In 21 of the 29 patients (72%) with hypothyroidism
      who received thyroid hormone replacement therapy, the volume, mean parenchymal
      density, SUVmax, and TLG of the thyroid glands showed no significant changes. In
      contrast, 8 of the 29 patients (28%) who did not receive thyroid hormone
      replacement therapy showed marked decreases in SUVmax and TLG. CONCLUSION:
      Diffuse thyroid uptake on PET-CT represents active inflammation caused by chronic
      thyroiditis in patients with advanced breast carcinoma. Diffuse thyroid uptake
      may also address the concern about subclinical hypothyroidism which develops into
      overt disease during follow-up.

PMID- 19156412
TI  - 'Intensity diffusion' is a better description than 'partial volume effect'.

PMID- 19156411
TI  - Nuclear imaging in cardiac amyloidosis.
AB  - Amyloidosis is a disease characterized by depositions of amyloid in organs and
      tissues. It can be localized (in just one organ) or systemic. Cardiac amyloidosis
      is a debilitating disease and can lead to arrhythmias, deterioration of heart
      function and even sudden death. We reviewed PubMed/Medline, without time
      constraints, on the different nuclear imaging modalities that are used to
      visualize myocardial amyloid involvement. Several SPECT tracers have been used
      for this purpose. The results with these tracers in the evaluation of myocardial
      amyloidosis and their mechanisms of action are described. Most clinical evidence
      was found for the use of (123)I-MIBG. Myocardial defects in MIBG activity seem to
      correlate well with impaired cardiac sympathetic nerve endings due to amyloid
      deposits. (123)I-MIBG is an attractive option for objective evaluation of cardiac
      sympathetic level and may play an important role in the indirect measurement of
      the effect of amyloid myocardial infiltration. Other, less sensitive, options are
      (99m)Tc-aprotinin for imaging amyloid deposits and perhaps (99m)Tc-labelled
      phosphate derivatives, especially in the differential diagnosis of the aetiology
      of cardiac amyloidosis. PET tracers, despite the advantage of absolute
      quantification and higher resolution, are not yet well evaluated for the study of
      cardiac amyloidosis. Because of these advantages, there is still the need for
      further research in this field.

PMID- 19156414
TI  - Pegylated liposomal doxorubicin (CAELYX) in patients with advanced ovarian
      cancer: results of a German multicenter observational study.
AB  - PURPOSE: Pegylated liposomal doxorubicin (PLD, CAELYX) has demonstrated activity
      in several phase-III trials and has been approved for the therapy of relapsed
      ovarian cancer after platinum treatment. Aim of this observational study was to
      analyze the efficacy and toxicity profile of PLD under routine clinical
      conditions and without the general restrictions of defined inclusion and
      exclusion criteria of clinical trials. METHODS: Between 2003 and 2005, a total of
      190 patients with relapsed ovarian cancer were enrolled. 183 patients were
      available for evaluation; dose-intensity, modifications, treatment duration,
      toxicities and response were systematically analyzed. RESULTS: The median patient
      age was 62 years (range 23-86 years). 45.4% of the patients received PLD as
      second-line therapy and a median of four courses per patient were administered.
      The median dose of PLD was 40 mg/m(2), most frequently used every 4 weeks
      (68.8%). Grade 3 Leucopenia (1.6%) and grade 3 and 4 thrombocytopenia (0.5%) were
      the most frequent hematological toxicities. The most frequent non-hematological
      toxicities were skin toxicity, pain and nausea, which were observed in 38.8, 41
      and 45.9% of the patients, respectively. Twenty-seven percent of the patients
      showed a response to therapy with 6.9% achieving complete remission and 20.1%
      achieving partial remission. 37.7% achieved a stable disease. The median duration
      of response for all patients was 4.8 months (range 0-51.8 months). Median
      progression-free interval and overall survival were 5.8 months (95% CI 5.1-6.6
      months) and 16.6 months (95% CI 13.9-22.6 months), respectively. CONCLUSIONS: PLD
      is safe and effective in patients with relapsed ovarian cancer, even after
      numerous previous treatment regimens. A dose of 40 mg/m(2) every 28 days seems to
      be an effective and well-tolerated therapeutic option in advanced ovarian cancer
      with a low incidence of hematological toxicities and acceptable non-hematological
      toxicities.

PMID- 19156413
TI  - Type-1 polarized dendritic cells primed for high IL-12 production show enhanced
      activity as cancer vaccines.
AB  - While multiple pathways of dendritic cell (DC) maturation result in transient
      production of IL-12, fully mature DCs show reduced ability to produce IL-12p70
      upon a subsequent interaction with Ag-specific T cells, limiting their in vivo
      performance as vaccines. Such "DC exhaustion" can be prevented by the presence of
      IFNgamma during the maturation of human DCs (type-1-polarization), resulting in
      improved induction of tumor-specific Th1 and CTL responses in vitro. Here, we
      show that type-1 polarization of mouse DCs strongly enhances their ability to
      induce CTL responses against a model tumor antigen, OVA, in vivo, promoting the
      induction of protective immunity against OVA-expressing EG7 lymphoma.
      Interestingly, in contrast to the human system, the induction of mouse DC1s
      requires the participation of IL-4, a nominal Th2-inducing cytokine. The current
      data help to explain the previously reported Th1-driving and anti-tumor
      activities of IL-4, and demonstrate that type-1 polarization increases in vivo
      activity of DC-based vaccines.

PMID- 19156415
TI  - Sequential development of mutant clones in an imatinib resistant chronic myeloid
      leukaemia patient following sequential treatment with multiple tyrosine kinase
      inhibitors: an emerging problem?
AB  - With the increasing use of new tyrosine kinase inhibitors it has been suggested
      that the spectrum of kinase domain mutations may change and possible selection of
      new resistant clones may occur. We describe a Ph + chronic myeloid leukaemia
      (CML) patient with primary resistance to imatinib who received without success
      sequential therapy with multiple TKIs, and developed sequential emergence of
      kinase domain mutations after these treatments.

PMID- 19156416
TI  - Diffusion approximations for one-locus multi-allele kin selection, mutation and
      random drift in group-structured populations: a unifying approach to selection
      models in population genetics.
AB  - Diffusion approximations are ascertained from a two-time-scale argument in the
      case of a group-structured diploid population with scaled viability parameters
      depending on the individual genotype and the group type at a single multi-allelic
      locus under recurrent mutation, and applied to the case of random pairwise
      interactions within groups. The main step consists in proving global and uniform
      convergence of the distribution of the group types in an infinite population in
      the absence of selection and mutation, using a coalescent approach. An inclusive
      fitness formulation with coefficient of relatedness between a focal individual J
      affecting the reproductive success of an individual I, defined as the expected
      fraction of genes in I that are identical by descent to one or more genes in J in
      a neutral infinite population, given that J is allozygous or autozygous, yields
      the correct selection drift functions. These are analogous to the selection drift
      functions obtained with pure viability selection in a population with inbreeding.
      They give the changes of the allele frequencies in an infinite population without
      mutation that correspond to the replicator equation with fitness matrix expressed
      as a linear combination of a symmetric matrix for allozygous individuals and a
      rank-one matrix for autozygous individuals. In the case of no inbreeding, the
      mean inclusive fitness is a strict Lyapunov function with respect to this
      deterministic dynamics. Connections are made between dispersal with exact
      replacement (proportional dispersal), uniform dispersal, and local extinction and
      recolonization. The timing of dispersal (before or after selection, before or
      after mating) is shown to have an effect on group competition and the effective
      population size.

PMID- 19156417
TI  - [Cholesterol ester storage disease: a rare disease or a rare diagnosis?].
AB  - We report the case of a 13-year-old boy with a longstanding history of unspecific
      hepatomegaly. The morphological investigations were diagnostic of a cholesterol
      ester storage disease (CESD), a rare autosomal recessive inherited disease with
      deficient activity of lysosomal acid lipase (LAL). The combination of
      hepatomegaly with accumulation of macrophages and ultrastructural evidence of
      lysosomal lipid storage are groundbreaking for the diagnosis. The probability of
      a underdiagnosis or false disease classification, for example as nonalcoholic
      steatohepatitis (NASH), is high, particularly with regard to genetic data which
      indicate a higher incidence of the disease.

PMID- 19156418
TI  - [Atypical ductal hyperplasia and atypical epithelial proliferation of ductal
      type].
AB  - The definition of atypical ductal hyperplasia (ADH) encompasses qualitative and
      quantitative criteria. Qualitative criteria include cytological and architectural
      features similar to those of low grade ductal carcinoma in situ (DCIS), the
      quantitative criteria are characterized by metric features (2 mm or 2 ductules)
      or by the confines of lobules. In this article we discuss the morphology of ADH,
      the status of ADH in the low grade pathway of breast carcinoma development and
      its clinical significance. Furthermore, we comment some special forms of atypical
      epithelial proliferations of the ductal type.

PMID- 19156419
TI  - Massive lower gastrointestinal haemorrhage, successfully treated with
      corticosteroids, as main symptom of Schonlein-Henoch purpura.
AB  - Schonlein-Henoch purpura is a small vessel disease that affects mainly skin and
      kidney, although several gastrointestinal symptoms may occur including abdominal
      pain, intussusception, perforation or bleeding. Massive lower gastrointestinal
      haemorrhage is rare and even more as the main symptom of the disease. We present
      a case of a 2-year-old boy with Schonlein-Henoch purpura who developed a massive
      lower gastrointestinal bleeding requiring blood transfusion. In this patient both
      Schonlein-Henoch purpura and gastrointestinal haemorrhage were successfully
      treated with intravenous methylprednisolone, avoiding surgical intervention.
      Physicians need to have a high index of suspicion when evaluating these patients,
      even more when dermatologic signs are scarce. Glucocorticosteroid therapy may be
      effective when treating severe gastrointestinal symptoms.

PMID- 19156420
TI  - Non-tuberculous mycobacterial osteomyelitis: an unusual cause of hip pain in
      immunocompetent children.
AB  - Non-tuberculous mycobacteria (NTM) are an unusual cause of osteomyelitis in
      immunocompetent children. Diagnosis is often difficult due to the paucity of
      clinical symptoms and a subtle course of the disease. NTM comprise a group of
      about 91 identified species of environmental mycobacteria that cause infections
      most frequently in immunocompromised individuals or in patients with predisposing
      factors. Cervical lymphadenitis is the most common presentation of NTM infection
      in children. Invasive and recurrent infections with these organisms have been
      associated with a genetic defect of the interferon gamma-receptor. We report a 3
      year-old immunocompetent girl who presented a NTM osteomyelitis of the left
      femur. Four months before she had been treated with medical and surgical therapy
      for a mycobacterium avium complex cervical lymphadenitis. Polymerase chain
      reaction assay on bone aspirate specimens confirmed the diagnosis of
      mycobacterium avium osteomyelitis. The patient was treated successfully with
      clarithromycin and rifampicin for 6 months.

PMID- 19156421
TI  - Methotrexate treatment ameliorated testicular suppression and anorexia related
      leptin reduction in rats with adjuvant arthritis.
AB  - Methotrexate (MTX) has been frequently used in the treatment of rheumatoid
      arthritis (RA). However, its action on arthritis associated male hypogonadism, or
      anorexia related low leptin production has not yet been studied. The well
      established model of human RA is rat adjuvant-induced arthritis (AA). In the
      present series we aimed at the evaluation of the effects of MTX on AA induced
      inflammatory parameters, testosterone suppression, and anorexia associated
      lowered leptin release. AA was induced in male Lewis rats by intradermal
      injection of heat killed Mycobacterium butyricum in incomplete Freund's adjuvant
      in the base of the tail. Arthritic rats were treated with two doses of MTX: 0.3
      and 0.5 mg/kg twice a week orally for the period of 28 days. The evaluated
      parameters were body mass, hind-paw swelling, arthrogram scores, serum albumin,
      total testosterone and leptin on days 14, 21 and 28 of AA. MTX treatment
      ameliorated all parameters studied dose dependently. Higher dose of MTX induced a
      significant reduction in the hind-paw swelling, arthritic score, and an increase
      in serum albumin in all examined time intervals of AA. This dose also
      significantly improved the suppressed testosterone and leptin levels found in
      arthritic rats. Prophylactic MTX treatment of rats with AA improved all
      inflammatory and arthritic parameters studied indicating its clear anti
      inflammatory effects. The significant improvement of testosterone and leptin
      shows beneficial effects of MTX on reproduction and anorexia related leptin
      reduction during chronic AA.

PMID- 19156422
TI  - Hemolytic uremic syndrome with ischemic glomerulonephropathy and obliterative
      vasculopathy in a systemic sclerosis patient treated with cyclosporine-A.
AB  - Hemolytic uremic syndrome (HUS) is not a commonly reported complication in post
      transplantation patients treated with cyclosporine-A (CSA), and is extremely rare
      in systemic sclerosis (SSc) patients treated with this drug. CSA may contribute
      to the development of chronic ischemic glomerulonephropathy and vasculopathy,
      features not easily distinguished from SSc-related nephropathy. Here, we describe
      a 41-year-old Chinese man with diffuse-type SSc treated with CSA who developed
      thrombocytopenia, acute renal failure and hemolytic anemia and was diagnosed with
      HUS. Renal function and thrombocytopenia improved gradually after intensive
      treatment of plasma exchange (PE) and high-dose steroid therapy. After PE, renal
      biopsy showed ischemic glomerulonephropathy and obliterative vasculopathy. This
      case illustrates that PE can improve the hematological disorders and
      characteristic renal changes of HUS in SSc patients treated with CSA. However,
      this therapy may not be effective in normalizing serum creatinine level in SSc
      patients once CSA has triggered the normal kidney to develop glomerulonephropathy
      and vasculopathy with ischemic and sclerotic changes.

PMID- 19156423
TI  - The value of 18F-DOPA PET-CT in patients with medullary thyroid carcinoma:
      comparison with 18F-FDG PET-CT.
AB  - The purpose of this prospective study was to compare the value of DOPA PET-CT
      with FDG PET-CT in the detection of malignant lesions in patients with medullary
      thyroid carcinoma (MTC). Twenty-six consecutive patients (10 men, 16 women, mean
      age 59 +/- 14 years) with elevated calcitonin levels were evaluated in this
      prospective study. DOPA and FDG PET-CT modalities were performed within a maximum
      of 4 weeks (median 7 days) in all patients. The data were evaluated on a patient-
      and lesion-based analysis. The final diagnosis of positive PET lesions was based
      on histopathological findings and/or imaging follow-up studies (i.e., DOPA and/or
      FDG PET-CT) for at least 6 months (range 6-24 months). In 21 (21/26) patients at
      least one malignant lesion was detected by DOPA PET, while only 15 (15/26)
      patients showed abnormal FDG uptake. DOPA PET provided important additional
      information in the follow-up assessment in seven (27%) patients which changed the
      therapeutic management. The patient-based analysis of our data demonstrated a
      sensitivity of 81% for DOPA PET versus 58% for FDG PET, respectively. In four
      (4/26) postoperative patients DOPA and FDG PET-CT studies were negative in spite
      of elevated serum calcitonin and CEA levels as well as abnormal pentagastrin
      tests. Overall 59 pathological lesions with abnormal tracer uptake were seen on
      DOPA and/or FDG PET studies. In the final diagnosis 53 lesions proved to be
      malignant. DOPA PET correctly detected 94% (50/53) of malignant lesions, whereas
      only 62% (33/53) of malignant lesions were detected with FDG PET. DOPA PET-CT
      showed superior results to FDG PET-CT in the preoperative and follow-up
      assessment of MTC patients. Therefore, we recommend DOPA PET-CT as a one-stop
      diagnostic procedure to provide both functional and morphological data in order
      to select those patients who may benefit from (re-)operation with curative intent
      as well as guiding further surgical procedures.

PMID- 19156424
TI  - CT and clinical features of hemorrhage extending along the pulmonary artery due
      to ruptured aortic dissection.
AB  - The purpose was to evaluate CT findings of hemorrhage extending along the
      pulmonary artery (PA) due to ruptured aortic dissection (AD) and its prognostic
      factors. In 232 patients with Stanford type A AD, 21 patients (9.1%; 11 women;
      mean 70.3 years) were diagnosed. Twelve patients had double-barreled (classic)
      AD, and nine patients had intramural hematoma (IMH; closed false lumen) of the
      aorta. Based on CT findings, hemorrhage was classified into three categories as
      follows: category 1 (IMH of the PA or blood localized around the PA), category 2
      (extending into the interlobular septa), and category 3 (extending into the
      alveoli). The factors influencing prognosis, including CT features and patient
      characteristics, were evaluated. Fourteen (66.7%) of the 21 patients underwent
      emergency surgery, and 8 (38.1%) patients died within 72 h of onset. Twelve cases
      (57.1%) were classified into category 1, 2 cases (9.5%) into category 2, and 7
      cases (33.3%) into category 3. Double-barreled AD and category 3 hemorrhage were
      significant risk factors for death in univariate analyses. In multivariate
      analyses, the presence of category 3 hemorrhage was the only significant risk
      factor for death. CT findings indicative of a poor prognosis include double
      barreled type AD and category 3 hemorrhage.

PMID- 19156425
TI  - Unjustified CT examinations in young patients.
AB  - The doses of radiation from computed tomography (CT) are relatively high, yet CT
      is being increasingly utilized. Furthermore, the radiation-induced lifetime risk
      of cancer mortality is higher at younger age. The purpose of this study was to
      find out whether previous CT examinations done on patients aged under 35 years
      were justified, and if not, whether there would have been other, more justifiable
      imaging modalities available. Fifty CT examinations of the head and 30 CT
      examinations each of the lumbar spine, cervical spine, abdomen, nasal sinuses and
      trauma were evaluated consecutively since the beginning of the year 2005 by using
      electronic patient files, the referral guidelines for imaging recommended by the
      European Commission and certain principles of classification. Seventy-seven per
      cent of the CT examinations of the lumbar spine, 36% of the head, 37% of the
      abdomen, 20% of the nasal sinuses and 3% of the cervical spine were unjustified.
      Most of these unjustified examinations could have been replaced by magnetic
      resonance imaging. In order to reduce utilization of ionizing radiation, both the
      referring practitioner and the radiologist responsible for the examination should
      carefully consider the justification for CT examinations and the possibility of
      using other imaging modalities.

PMID- 19156426
TI  - [Optical coherence tomography for macula diagnostics. Review of methods and
      standardized application concentrating on diagnostic and therapy control of age
      related macula degeneration].
AB  - BACKGROUND: Optical coherence tomography (OCT) has gained increasing relevance
      for follow-up after the treatment of macular diseases especially after anti-VEGF
      therapy. Therefore it seemed reasonable to develop standardized evaluation
      strategies and OCT examination guidelines for Stratus OCT III. MATERIALS AND
      METHODS: Basic guidelines for the Stratus OCT III examination of macular diseases
      were developed. The first part contains basic advice for the OCT examination with
      respect to the examiner, patients, image quality, movement artefacts, algorithms,
      archiving and interpretation of OCT images. The second part consists of the
      relevance and indications for OCT examination especially in age-related macular
      degeneration (AMD), subgroups of AMD and follow-up after treatment. The third
      part demonstrates a brief outlook on future developments, such as the digital
      integration method (DIM), which provides identical scan localization in follow-up
      and eliminates any movement artefacts. CONCLUSION: The application of
      standardized routine scanning and analysis protocols in Stratus OCT III for
      macular diseases and follow-up examinations provides an optimized, time-saving
      and comparable use of OCT. Therefore, the relevance and quality of OCT is
      increased for routine use in outpatient departments, hospitals and also for
      clinical studies.

PMID- 19156427
TI  - [Retrospective investigation of seasonal factors influencing intraocular pressure
      in glaucoma patients].
AB  - BACKGROUND: Some studies in the literature claim a significant seasonal variation
      of intraocular pressure (IOP) due to the influence of various factors. The aim of
      our study was to examine such influences on IOP in the Caucasian population.
      PATIENTS AND METHODS: For a period of 12 years, the data of 172 glaucoma patients
      from the outpatient glaucoma clinic of the Technical University of Munich were
      retrospectively evaluated. Most patients had been medically treated to lower
      their IOP. RESULTS: Slight seasonal variations were found, with the months of low
      sunlight correlating with higher measurements than the months of high sunlight.
      The statistical significance of seasonal variation shown in other studies could
      not be confirmed in this study. CONCLUSION: The seasonal variation of IOP was not
      statistically significant in our population. A reason for this finding could be
      that the patients were using glaucoma medication.

PMID- 19156428
TI  - [Cone dystrophy--of the significance of a minority of photoreceptors].

PMID- 19156429
TI  - Extra-hepatic biliary-ductal necrosis following acute pancreatitis: 10 years of
      follow-up.
AB  - This case report is 10 years follow-up of a child who presented with acute
      abdomen at the age of 8 years. Exploration revealed acute pancreatitis with the
      necrosis of common bile duct and almost whole of the common hepatic duct with
      bile leaking from the junctional stump of the right and left hepatic ducts. The
      patient was managed successfully by Roux-en-Y hepaticojejunostomy. After 10
      years, the patient again presented with a recurrent discharging sinus from the
      anterior abdominal wall. On exploration, it was found to be a stitch granuloma
      near the site of hepaticojejunostomy. However, hepaticojejunostomy was found to
      function normally as seen on MRCP. This rare case highlights that extra-hepatic
      biliary-ductal necrosis is very unusual complication of acute pancreatitis; and
      it can be successfully managed by Roux-en-Y hepaticojejunostomy as evident from
      long-term follow-up.

PMID- 19156430
TI  - Feasibility of complex minimally invasive surgery in neonates.
AB  - The aim of this study was to assess the feasibility of complex minimally invasive
      surgery in neonates (and infants <5 kg). A systematic search of databases was
      performed. Inguinal herniotomy and pyloromyotomy were specifically excluded.
      Various operations were assessed for operative times, conversion rates,
      complications and centres performing the procedures. From 479 abstracts, 50
      papers were identified describing 1,215 patients. Common operations performed
      were fundoplication (n = 473), operations for ovarian pathology (n = 151) and
      oesophageal atresia repair (n = 123). Other not-so-common operations included
      Kasai procedure (n = 61), Ladd's procedure (n = 55), bowel atresia surgery (n =
      45) and congenital diaphragmatic hernia repair (n = 41). Mean operation times
      varied from 43 min for fundoplication to 209 min for Kasai procedure, with other
      operation times falling in between the two extremes. Likewise, conversion rates
      varied from 0.2% for fundoplication to 15% for congenital diaphragmatic hernia,
      with other conversion rates falling in between. Complications ranged from 0 to
      67%. About 70-94% of the cases were performed in six pioneering centres.
      Fundoplication and operations for ovarian pathology have low complication and
      conversion rates and appear to be well suited to the average-trained paediatric
      laparoscopic surgeon. More complex procedures are feasible and safe, but
      technically demanding and need further expertise.

PMID- 19156431
TI  - Occurrence and prognostic value of circumferential resection margin involvement
      for patients with rectal cancer.
AB  - BACKGROUND AND AIM: Total mesorectal excision (TME) was advocated owning to the
      reduction in local failure, while deficiency in pathologic details limited
      monitoring of surgical quality assurance. Here, we aimed to examine
      circumferential resection margin (CRM) by large tissue slice, discussing its rule
      in occurrence and relationship with prognosis, thus providing proof for the
      adoption of TME principles and the application of adjuvant therapy. MATERIALS AND
      METHODS: Specimens of 106 patients with rectal cancer, who underwent potentially
      curative resection from December 2001 to September 2002, were examined. Follow-up
      data were collected. RESULTS: Altogether, 2,068 mesorectal nodes were examined
      with 272 involved by tumor. CRM involvement (CRMI) was examined in 20 specimens.
      In these 20 cases, seven, nine, and four were caused by tumor infiltration, lymph
      node metastasis, and both, respectively. Occurrence of CRMI was more common for
      lower-located cancers while also statistically related to tumor differentiation,
      infiltration, and lymph node metastasis. The difference in local recurrence rate,
      general recurrence rate, disease-free survival rate, and overall survival rate
      between the group with CRMI and the group without were all proven to be
      significant. CONCLUSIONS: Detailed pathologic examination, including status of
      CRM, is advocated since it provides accurate prognostic information. Surgeons
      could maximize the probability of cure by following the principle of TME.
      Preoperative adjuvant therapy was essential for advanced staged and lower-located
      lesions, which implied likelihood of CRMI.

PMID- 19156432
TI  - [Leg ulcer in mixed connective tissue disease. Resolution during sitaxsentan
      therapy].
AB  - Leg ulcers may result in serious morbidity in patients with connective tissue
      diseases and Raynaud's phenomenon (RP). We describe a 35-year-old woman with
      mixed connective tissue disease who suffered from leg ulcers refractory to
      iloprost. When the patient was treated with the selective endothelin A receptor
      antagonist sitaxsentan for pulmonary arterial hypertension, the ulcers improved
      within 4 weeks and resolved completely thereafter. In addition, severity of RP
      ameliorated markedly. Further evaluation of sitaxsentan in patients with
      connective tissue diseases suffering from ischemic skin ulcers is required.

PMID- 19156433
TI  - [Treatment outcome parameters].

PMID- 19156434
TI  - Meiosis study in a population sample from Nigeria: allele frequencies and
      mutation rates of 16 STR loci.
AB  - Allele frequencies for the 16 short tandem repeat (STR) loci D2S1338, D3S1358,
      D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11, ACTBP2,
      CSF1PO, FGA, TH01, TPOX and VWA were determined for 337 immigrants from Nigeria.
      All loci were in Hardy-Weinberg equilibrium. More than 6,000 meiotic transfers
      were investigated and ten mutations were observed. Single mutations were observed
      in the STR systems D2S1338, D3S1358, D7S820, D8S1179, D16S539 and FGA, whereas
      two mutations were observed in the systems D21S11 and VWA.

PMID- 19156435
TI  - Preoperative duration of retinal detachment and preoperative central retinal
      artery hemodynamics: repercussion on visual acuity.
AB  - PURPOSE: To analyze if preoperative duration of primary rhegmatogenous retinal
      detachment (RD) influences preoperative central retinal artery (CRA) hemodynamics
      with repercussions on logarithmic (LogMAR) visual acuity (VA). METHODS:
      Prospective clinical cohort study on 66 healthy patients (33 with proliferative
      vitreoretinopathy (PVR) and 33 with no PVR) with unilateral RD candidates for
      scleral buckling (SB) surgery (PVR <C3) as a first and single surgical procedure.
      CRA Doppler sonography parameters (peak systolic, end diastolic velocities and
      resistibility index) and IOP were measured before SB. Pearson's correlations were
      evaluated between preoperative RD duration and each preoperative CRA parameter,
      and also between both variables and the LogMAR VAs (preoperative, postoperative 8
      months, and the difference: postoperative 8 months minus preoperative). RESULTS:
      Preoperative duration of RD was correlated (with statistical significance both
      PVR and no PVR) with pre- and postoperative 8 months LogMAR VAs (both positive
      correlations), with preoperative IOP (negative correlation), and with
      preoperative CRA parameters (negative correlations with CRA velocities and
      positive correlation with resistibility index). Preoperative CRA parameters
      (correlated with preoperative IOP in PVR) were correlated (negatively for CRA
      velocities and positively for CRA RI) with LogMAR VAs (preoperative,
      postoperative 8 months, and difference) in PVR. The average preoperative RD
      duration was longer in the PVR group than in the no PVR group (p < 0.0001). A
      longer preoperative RD duration was associated with macula-off in both groups.
      Macula-off and PVR respectively showed lower preoperative IOP and lower
      preoperative CRA velocities than macula-on and no PVR. CONCLUSIONS: Preoperative
      CRA parameters and LogMAR VAs (pre-, and postoperative 8 months) were influenced
      by preoperative RD duration in both no PVR and PVR. Preoperative CRA parameters
      were correlated with LogMAR VAs (pre-, postoperative 8 months, and the
      difference) only in PVR. Postoperative 8 months and preoperative LogMAR VAs were
      only correlated (with statistical significance) in macula-on cases of both the
      PVR and no PVR groups.

PMID- 19156436
TI  - Synthesis and intracellular transportation of type I procollagen during
      functional differentiation of odontoblasts.
AB  - The expression of type I collagen, the most component of dentin extracellular
      matrix proteins (ECMs) in odontoblast is correlated with the activity of dentin
      formation. Since odontoblast possesses a distinct cellular process for protein
      transport into the dentinal tubule, it is important to examine the intracellular
      protein localization. However, a study focusing on odontoblast processes has not
      been performed. Type I collagen is synthesized as procollagen, which is
      immediately converted to collagen upon secretion. After characterization of
      antiserum to rat type I procollagen, we investigated the intracellular
      localization of type I procollagen in odontoblasts during and after
      dentinogenesis, using immunohistochemistry and in situ hybridization. The level
      of mRNA expression decreased during dentinogenesis, whereas the intracellular
      localization of type I procollagen in odontoblast processes become more distinct.
      The percentage of dentinal tubules with type I procollagen increased
      significantly with aging. Odontoblasts in pulp horn, in particular, showed
      moderate expression of type I procollagen after dentinogenesis. Since loss of
      occlusion also caused a significant decrease in type I procollagen, we concluded
      that occlusal stimulation activated type I procollagen synthesis in odontoblasts.
      We also suggest that analysis of intracellular transport of type I procollagen
      via odontoblast processes may be a new approach to evaluation of odontoblast
      function.

PMID- 19156437
TI  - Change in body mass accurately and reliably predicts change in body water after
      endurance exercise.
AB  - This study tested the hypothesis that the change in body mass (DeltaBM)
      accurately reflects the change in total body water (DeltaTBW) after prolonged
      exercise. Subjects (4 men, 4 women; 22-36 year; 66 +/- 10 kg) completed 2 h of
      interval running (70% VO(2max)) in the heat (30 degrees C), followed by a run to
      exhaustion (85% VO(2max)), and then sat for a 1 h recovery period. During
      exercise and recovery, subjects drank fluid or no fluid to maintain their BM,
      increase BM by 2%, or decrease BM by 2 or 4% in separate trials. Pre- and post
      experiment TBW were determined using the deuterium oxide (D(2)O) dilution
      technique and corrected for D(2)O lost in urine, sweat, breath vapor, and
      nonaqueous hydrogen exchange. The average difference between DeltaBM and DeltaTBW
      was 0.07 +/- 1.07 kg (paired t test, P = 0.29). The slope and intercept of the
      relation between DeltaBM and DeltaTBW were not significantly different from 1 and
      0, respectively. The intraclass correlation coefficient between DeltaBM and
      DeltaTBW was 0.76, which is indicative of excellent reliability between methods.
      Measuring pre- to post-exercise DeltaBM is an accurate and reliable method to
      assess the DeltaTBW.

PMID- 19156438
TI  - Attention, competition, and the parietal lobes: insights from Balint's syndrome.
AB  - Simultanagnosia (resulting from occipito-parietal damage) is a profound visual
      deficit, which impairs the ability to perceive multiple items in a visual
      display, while preserving the ability to recognise single objects. Here we
      demonstrate in a patient presenting with Balint's syndrome that this deficit may
      result from an extreme form of competition between objects which makes it
      difficult for attention to be disengaged from an object once it has been
      selected.

PMID- 19156439
TI  - Putative regulatory mechanism of prothoracicotropic hormone (PTTH) secretion in
      the American cockroach, Periplaneta americana as inferred from co-localization of
      Rab8, PTTH, and protein kinase C in neurosecretory cells.
AB  - Small GTPases of the Rab family act as essential regulators of vesicle transport
      pathways, including the exocytosis of neurohormones. These processes are not well
      understood in insects. To address the physiological function of Rab proteins and
      their phosphorylation in insect neurosecretion, Rab8-like, prothoracicotropic
      hormone (PTTH)-like, and protein kinase C (PKC)-like immunohistochemical
      reactivities (-ir) were investigated in the brain of the American cockroach,
      Periplaneta americana. All the antibodies tested reacted with neurons in the pars
      intercerebralis, corpora cardiaca, and nervi corporis allati I. Double-labeling
      experiments demonstrated that all PTTH-ir were colocalized with Rab8-ir and PKC
      ir in the pars intercerebralis, although exclusive reactivity was present to
      antisera against Rab8 or PKC. These findings support the notion that Rab8-like
      antigen is phosphorylated by PKC, and that this phosphorylation is involved in
      the axonal transport and secretion of PTTH in this species.

PMID- 19156440
TI  - Gamma-aminobutyric acid immunostaining in the antennal lobe of the moth Heliothis
      virescens and its colocalization with neuropeptides.
AB  - The antennal lobe is the primary processing center for olfactory information in
      insects. To understand further the neural circuitry of this brain area, we have
      investigated the distribution of gamma-aminobutyric acid (GABA) and its
      colocalization with neuropeptides in the antennal lobe of the noctuid moth
      Heliothis virescens. Immunocytochemical experiments with an antiserum against
      GABA showed a large number of labeled somata in the antennal lobe; these somata
      were located exclusively in the lateral cell cluster. Stained neurites
      innervating all antennal-lobe glomeruli, including the male-specific
      macroglomerular complex, suggested a prominent role of GABA in processing
      olfactory information, including signals from pheromones, interspecifically
      acting odors, and plant odors. Fibers in two antennocerebral tracts (the middle
      and dorsal antennocerebral tract) exhibited prominent GABA immunoreactivity.
      Double-labeling experiments revealed that immunostaining for three neuropeptides,
      viz., A-type allatostatin, Manduca sexta allatotropin, and FMRFamide-related
      peptides, was largely colocalized with GABA in cell bodies of the lateral cell
      cluster. The general absence of peptide immunostaining in the antennocerebral
      tracts strongly indicated that these peptides were colocalized with GABA in local
      interneurons of the antennal lobe. In contrast, tachykinin-related peptides
      occurred in a distinct population of local antennal-lobe neurons that did not
      exhibit GABA immunostaining. Thus, local interneurons that were not GABAergic
      were present in the moth antennal lobe.

PMID- 19156441
TI  - Effects of hyperglycemia and oxidative stress on the glutamate transporters GLAST
      and system xc- in mouse retinal Muller glial cells.
AB  - Elevated glutamate levels have been reported in humans with diabetic retinopathy.
      Retinal Muller glial cells regulate glutamate levels via the GLAST transporter
      and system x(c)(-) (cystine-glutamate exchanger). We have investigated whether
      transporter function and gene and/or protein expression are altered in mouse
      Muller cells cultured under conditions of hyperglycemia or oxidative stress (two
      factors implicated in diabetic retinopathy). Cells were subjected to
      hyperglycemic conditions (35 mM glucose) over an 8-day period or to oxidative
      stress conditions (induced by exposure to various concentrations of
      xanthine:xanthine oxidase) for 6 h. The Na(+)-dependent and -independent uptake
      of [(3)H] glutamate was assessed as a measure of GLAST and system x(c)(-)
      function, respectively. Hyperglycemia did not alter the uptake of [(3)H]
      glutamate by GLAST or system x(c)(-); neither gene nor protein expression
      decreased. Oxidative stress (70:14 or 100:20 microM xanthine:mU/ml xanthine
      oxidase) decreased GLAST activity by approximately 10% but increased system x(c)(
      ) activity by 43% and 89%, respectively. Kinetic analysis showed an oxidative
      stress-induced change in V(max), but not K(m). Oxidative stress caused a 2.4-fold
      increase in mRNA encoding xCT, the unique component of system x(c)(-). Of the two
      isoforms of xCT (40 and 50 kDa), oxidative stress induced a 3.6-fold increase in
      the 40-kDa form localized to the plasma membrane. This is the first report of the
      differential expression and localization of xCT isoforms as caused by cellular
      stress. Increased system x(c)(-) activity in Muller cells subjected to conditions
      associated with diabetic retinopathy may be beneficial, as this exchanger is
      important for the synthesis of the antioxidant glutathione.

PMID- 19156442
TI  - Non-lethal effects of an invasive species in the marine environment: the
      importance of early life-history stages.
AB  - Studies examining the effects of invasive species have focussed traditionally on
      the direct/lethal effects of the invasive on the native community but there is a
      growing recognition that invasive species may also have non-lethal effects. In
      terrestrial systems, non-lethal effects of invasive species can disrupt early
      life-history phases (such as fertilisation, dispersal and subsequent
      establishment) of native species, but in the marine environment most studies
      focus on adult rather than early life-history stages. Here, we examine the
      potential for an introduced sessile marine invertebrate (Styela plicata) to exert
      both lethal and non-lethal effects on a native species (Microcosmus squamiger)
      across multiple early life-history stages. We determined whether sperm from the
      invasive species interfered with the fertilisation of eggs from the native
      species and found no effect. However, we did find strong effects of the invasive
      species on the post-fertilisation performance of the native species. The invasive
      species inhibited the settlement of native larvae and, in the field, the presence
      of the invasive species was associated with a ten-fold increase in the post
      settlement mortality of the native species, as well as an initial reduction of
      growth in the native. Our results suggest that larvae of the native species avoid
      settling near the invasive species due to reduced post-settlement survival in its
      presence. Overall, we found that invasive species can have complex and pervasive
      effects (both lethal and non-lethal) across the early life-history stages of the
      native species, which are likely to result in its displacement and to facilitate
      further invasion.

PMID- 19156443
TI  - Production of succinate by a pflB ldhA double mutant of Escherichia coli
      overexpressing malate dehydrogenase.
AB  - The gene encoding malate dehydrogenase (MDH) was overexpressed in a pflB ldhA
      double mutant of Escherichia coli, NZN111, for succinic acid production. With MDH
      overexpression, NZN111/pTrc99A-mdh restored the ability to metabolize glucose
      anaerobically and 0.55 g/L of succinic acid was produced from 3 g/L of glucose in
      shake flask culture. When supplied with 10 g/L of sodium bicarbonate (NaHCO(3)),
      the succinic acid yield of NZN111/pTrc99A-mdh reached 1.14 mol/mol glucose.
      Supply of NaHCO(3) also improved succinic acid production by the control strain,
      NZN111/pTrc99A. Measurement of key enzymes activities revealed that
      phosphoenolpyruvate (PEP) carboxykinase and PEP carboxylase in addition to MDH
      played important roles. Two-stage culture of NZN111/pTrc99A-mdh was carried out
      in a 5-L bioreactor and 12.2 g/L of succinic acid were produced from 15.6 g/L of
      glucose. Fed-batch culture was also performed, and the succinic acid
      concentration reached 31.9 g/L with a yield of 1.19 mol/mol glucose.

PMID- 19156444
TI  - Nephrolithiasis related to inborn metabolic diseases.
AB  - Nephrolithiasis associated with inborn metabolic diseases is a very rare
      condition with some common characteristics: early onset of symptoms, family
      history, associated tubular impairment, bilateral, multiple and recurrent stones,
      and association with nephrocalcinosis. The prognosis of such diseases may lead to
      life threatening conditions, not only because of unabated kidney damage but also
      because of progressive extra-renal involvement, either in a systemic form (e.g.
      primary hyperoxaluria type 1, requiring combined liver and kidney
      transplantation), or in a neurological form (Lesch-Nyhan syndrome leading to auto
      mutilation and disability, phosphoribosyl pyrophosphate synthetase superactivity,
      which is associated with mental retardation). Patients with other inborn
      metabolic diseases present only with recurrent stone formation, such as
      cystinuria, adenine phosphoribosyl-transferase deficiency, xanthine deficiency.
      Finally, nephrolithiasis may be secondarily part of some other metabolic
      diseases, such as glycogen storage disease type 1 or inborn errors of metabolism
      leading to Fanconi syndrome (nephropathic cystinosis, tyrosinaemia type 1,
      fructose intolerance, Wilson disease, respiratory chain disorders, etc.). The
      diagnosis is based on highly specific investigations, including crystal
      identification, biochemical analyses and DNA study. The treatment of
      nephrolithiasis requires hydration as well as specific measures. Compliance is a
      major issue regarding the progression of renal damage, but the overall outcome
      mainly depends on extra-renal involvement in relation to the metabolic defect.

PMID- 19156445
TI  - Continuous venovenous hemodiafiltration trace element clearance in pediatric
      patients: a case series.
AB  - Continuous renal replacement therapy (CRRT) is used to treat critically ill
      children with acute kidney injury. The effect of CRRT on trace element clearance
      is poorly characterized. The purpose of this study was to quantify the
      transmembrane clearance of chromium, copper, manganese, selenium and zinc during
      continuous venovenous hemodiafiltration (CVVHDF). The transmembrane clearance of
      trace elements was assessed prospectively in five critically ill children
      receiving CVVHDF at the pediatric intensive care unit of a tertiary care
      university hospital. Pre-filter blood and effluent samples were measured for
      trace element concentrations. Transmembrane clearance of trace elements was
      calculated, and daily loss of each trace element was determined. Daily trace
      element loss via CVVHDF was compared with daily standard supplementation of trace
      elements in pediatric parenteral nutrition. Five patients (age range 23 months to
      15 years) with a body weight range of 10.5-53 kg completed the study. The median
      transmembrane clearance of chromium, copper, manganese, selenium and zinc during
      CVVHDF was calculated as 0 ml, 0.59 ml, 2.48 ml, 1.22 ml, and 1.90 ml,
      respectively, per 1.73 m(2) body surface area per minute. The calculated CVVHDF
      losses were substantially smaller than the daily parenteral supplementation for
      all trace elements.

PMID- 19156446
TI  - [Ethics charter of the German Society for the Study of Pain].

PMID- 19156447
TI  - [Visualization of a myth--the new S3 guidelines for fibromyalgia syndrome].

PMID- 19156448
TI  - [Multimodal pain therapy: principles and indications].
AB  - Multimodal pain therapy describes an integrated multidisciplinary treatment in
      small groups with a closely coordinated therapeutical approach. Somatic and
      psychotherapeutic procedures cooperate with physical and psychological training
      programs. For chronic pain syndromes with complex somatic, psychological and
      social consequences, a therapeutic intensity of at least 100 hours is
      recommended. Under these conditions multimodal pain therapy has proven to be more
      effective than other kinds of treatment. If monodisciplinary and/or outpatient
      therapies fail, health insurance holders have a legitimate claim to this form of
      therapy.Medical indications are given for patients with chronic pain syndromes,
      but also if there is an elevated risk of chronic pain in the early stadium of the
      disease and aiming at delaying the process of chronification. Relative
      contraindications are a lack of motivation for behavioural change, severe mental
      disorders or psychopathologies and addiction problems. The availability of
      multimodal pain treatment centers in Germany is currently insufficient.

PMID- 19156450
TI  - Poster abstracts of the 4th triennial meeting of the European Federation of
      Conservative Dentistry (EFCD) held in association with the 17th annual meeting of
      the Spanish Society of Conservative Dentistry (SEOC), 12-14 March 2009, Seville,
      Spain.

PMID- 19156449
TI  - Calcareous amendments to soils to eradicate Tuber brumale from T. melanosporum
      cultivations: a multivariate statistical approach.
AB  - Calcareous amendments are being used in Tuber melanosporum truffle plantations in
      attempts to eradicate Tuber brumale. However, there are no studies available
      which provide soil analysis and statistical data on this topic. We studied 77
      soil samples to compare the values for carbonates, pH and total organic carbon in
      T. brumale truffieres with the values for T. melanosporum truffieres on
      contaminated farms and in natural areas. Statistical analyses indicate that the
      concentrations of active carbonate and total carbonate in the soil are
      significantly higher in T. brumale truffieres than in T. melanosporum truffieres,
      but that there are no significant differences in pH and total organic carbon. We
      conclude that liming would not suppress T. brumale ectomycorrhizas in
      contaminated T. melanosporum farms, and calcareous amendments do not therefore
      seem be a means of eradicating T. brumale in these farms.

PMID- 19156451
TI  - Whole-genome conditional two-locus analysis identifies novel candidate genes for
      late-onset Parkinson's disease.
AB  - Whole-genome epistasis analysis may add a new layer of knowledge to whole-genome
      association studies, permitting the identification of new candidate genes which
      are completely transparent during conventional single-locus analysis. We present
      the first whole-genome conditional two-locus analysis in Parkinson's disease
      (PD). We scanned the entire genome and selected markers that interacted with a
      set of well-known loci previously associated to PD (SNCA, Parkin, LRRK2, UCHL1,
      DJ-1, PINK and MAPT). Our work describes several loci potentially related to PD
      risk which interact with SNCA, PARK1 and LRRK2 markers. We propose conditional
      whole-genome two-locus association analysis as a valuable method that might be
      helpful in re-analysing and re-interpreting data from whole-genome association
      studies.

PMID- 19156453
TI  - Distribution of Legionella pneumophila serogroups, monoclonal antibody subgroups
      and DNA sequence types in recent clinical and environmental isolates from England
      and Wales (2000-2008).
AB  - Clinical isolates of Legionella pneumophila, obtained from 167 patients, who
      acquired their illness in the community in England and Wales between January 2000
      and March 2008, were compared with 276 environmental isolates of L. pneumophila
      obtained over the same period as part of the routine sampling of 'managed' water
      systems. The 443 isolates were typed by monoclonal antibody (mAb) subgrouping and
      the internationally standardised, seven-gene loci, sequence-based typing (SBT)
      scheme of the European Working Group for Legionella Infections (EWGLI). Of the
      clinical isolates, 97.6% were L. pneumophila serogroup (sgp) 1, compared with
      only 55.8% of environmental isolates (P = 0.0002); 91.6% were subgrouped as
      mAb3/1+ve, compared with only 8.3% of environmental isolates (P < 0.0001). The
      isolates were very diverse, with SBT identifying 111 sequence types (STs) (index
      of diversity [IOD] 0.954). Among the clinical isolates, 42 ST were seen, with one
      (ST47) accounting for 25.7% and three (ST47, ST37 and ST62) accounting for 46.1%
      of all isolates. Eighty-two STs were identified among the environmental isolates,
      with two (ST1 and ST79) accounting for 34.1% of these. Comparison of the STs seen
      among clinical and environmental isolates showed that there was very little
      overlap between the two populations (P < 0.0001), with common clinical strains
      found in the environment very infrequently: 0.4, 0.7 and 0% (ST47, ST37 and ST62,
      respectively), and common environmental strains rarely causing disease: 4.8 and
      1.2% (ST1 and ST79, respectively). Combining phenotypic and genotypic data
      identified 144 phenons (IOD 0.970); 52 among clinical isolates and 101 among
      environmental isolates. The most abundant clinical strain, mAb 'Allentown' ST47,
      accounted for 22.8% of cases, but was only found once in the environment.
      Conversely, mAb 'Oxford/OLDA' ST1 was the most common environmental strain
      (17.0%), but only caused two infections. A review of the published data shows
      that mAb 'Allentown' ST47 is also an important cause of infection in France and
      possibly in the Netherlands. However, it was not found in a large study of German
      clinical isolates. This study confirms previous work showing that just a few
      strains of L. pneumophila cause the majority of community-acquired Legionella
      infection in England and Wales, and that these clinically significant strains are
      only rarely found in managed water systems. These data suggest that knowing which
      particular strain is present in an environment might be at least as important as
      knowing the quantity in which legionellae are present.

PMID- 19156454
TI  - Matching the proteome to the genome: the microbody of penicillin-producing
      Penicillium chrysogenum cells.
AB  - In the filamentous fungus Penicillium chrysogenum, microbodies are essential for
      penicillin biosynthesis. To better understand the role of these organelles in
      antibiotics production, we determined the matrix enzyme contents of P.
      chrysogenum microbodies. Using a novel in silico approach, we first obtained a
      catalogue of 200 P. chrysogenum proteins with putative microbody targeting
      signals (PTSs). This included two orthologs of proteins involved in cephalosporin
      biosynthesis, which we demonstrate to be bona fide microbody matrix constituents.
      Subsequently, we performed a proteomics based inventory of P. chrysogenum
      microbody matrix proteins using nano-LC-MS/MS analysis. We identified 89
      microbody proteins, 79 with a PTS, including the two known microbody-borne
      penicillin biosynthesis enzymes, isopenicillin N:acyl CoA acyltransferase and
      phenylacetyl-CoA ligase. Comparative analysis revealed that 69 out of 79 PTS
      proteins identified experimentally were in the reference list. A prominent
      microbody protein was identified as a novel fumarate reductase-cytochrome b5
      fusion protein, which contains an internal PTS2 between the two functional
      domains. We show that this protein indeed localizes to P. chrysogenum
      microbodies.

PMID- 19156455
TI  - Assessment of a mechano-regulation theory of skeletal tissue differentiation in
      an in vivo model of mechanically induced cartilage formation.
AB  - Mechanical cues are known to regulate tissue differentiation during skeletal
      healing. Quantitative characterization of this mechano-regulatory effect has
      great therapeutic potential. This study tested an existing theory that shear
      strain and interstitial fluid flow govern skeletal tissue differentiation by
      applying this theory to a scenario in which a bending motion applied to a healing
      transverse osteotomy results in cartilage, rather than bone, formation. A 3-D
      finite element mesh was created from micro-computed tomography images of a
      bending-stimulated callus and was used to estimate the mechanical conditions
      present in the callus during the mechanical stimulation. Predictions regarding
      the patterns of tissues--cartilage, fibrous tissue, and bone--that formed were
      made based on the distributions of fluid velocity and octahedral shear strain.
      These predictions were compared to histological sections obtained from a previous
      study. The mechano-regulation theory correctly predicted formation of large
      volumes of cartilage within the osteotomy gap and many, though not all patterns
      of tissue formation observed throughout the callus. The results support the
      concept that interstitial fluid velocity and tissue shear strain are key
      mechanical stimuli for the differentiation of skeletal tissues.

PMID- 19156457
TI  - View from the other side of the white coat.

PMID- 19156456
TI  - Early dissimilar fates of liver eicosapentaenoic acid in rats fed liposomes or
      fish oil and gene expression related to lipid metabolism.
AB  - The study was undertaken to determine whether eicosapentaenoic acid (EPA, 20:5 n
      3) and docosahexaenoic acid (DHA, 22:6 n-3), esterified in phospholipids (PL) as
      liposomes or in triglycerides (TG) as oil, exhibited comparable fates in liver
      lipids and whether these fates were associated with gene expressions related to
      fatty acid (FA) metabolism. PL and TG mixtures with close contents in EPA and DHA
      were administered to rats over 2 weeks. Most relevant events occurred after 3
      days for both treatments. At that time, liposomes, compared with oil, increased
      the liver content in PL with a FA composition enriched in n-6 FA, comparable in
      DHA and much lower in EPA. Moreover, liposomes increased the activity and mRNA
      levels of carnitine palmitoyltransferase (CPT) I. In contrast, fish oil exerted
      opposite effects on CPT I and increased the genic expression of lipogenic
      enzymes. Liposomes, unlike fish oil, apparently increased the mRNA levels of acyl
      CoA oxidase and the activity of the peroxisomal FA-oxidising system.
      Concomitantly, mRNA levels of hepatic lipoprotein receptors were increased with
      both diets, but intracellular proteins involved in free FA uptake and lipid
      synthesis were up-regulated only with liposome-treated rats. The quasi absence of
      EPA in hepatic PL of liposome-treated rats on the short term could result from
      increased beta-oxidation activities through metabolic regulations induced by more
      available free EPA and other PUFA.

PMID- 19156458
TI  - Regenerative surgery: use of fat grafting combined with platelet-rich plasma for
      chronic lower-extremity ulcers.
AB  - BACKGROUND: The authors present their experience with reconstructive surgery of
      the lower extremity for chronic ulcers, evaluating the effects related to the use
      of a platelet-rich plasma combined with fat tissue. METHODS: A total of 20
      patients, 25 to 50 years of age (median age, 40 years), have been managed with
      platelet gel in the Plastic and Reconstructive Surgery Department at the "Tor
      Vergata," University of Rome. The patients were affected by both lower-extremity
      chronic ulcers and vascular disease. RESULTS: The authors observed that 16 of 20
      chronic lower-extremity ulcers reepithelialized during an average of 9.7 weeks,
      with platelet releasate suspended on a collagen base (platelet-derived wound
      healing factor), compared with 2 of 10 similar wounds treated with medication
      based on hyaluronic acid and collagen. Collectively, these data provide evidence
      for the clinical use of platelet technology in the healing of both soft and hard
      tissue wounds. CONCLUSIONS: Currently, plastic surgery with autogenous fat grafts
      can be performed for stabilization of chronic lower-extremity ulcers. The
      objective of this study was, through the presentation of clinical cases, to
      suggest a therapeutic plan formed by two sequential treatments: acquisition of
      platelet gel from a small volume of blood (9-18 ml) followed by the Coleman
      technique for reconstructing the three-dimensional projection and superficial
      density of tissues. The results proved the efficacy of combining these two
      treatments, and the satisfaction of the patients confirmed the quality of the
      results.

PMID- 19156459
TI  - Aesthetic remodeling of the healthy breast in breast reconstruction using
      expanders and implants.
AB  - BACKGROUND: Breast reconstruction using expanders and implants still is the most
      common surgical procedure in many hospitals. The most important factor in
      obtaining a satisfactory aesthetic result for both the patient and the surgeon is
      to achieve the greatest symmetry possible between the healthy breast and the
      reconstructed breast. To get a good result, it is necessary to make an exhaustive
      preoperative examination that facilitates selection of the most suitable
      technique for remodeling the healthy breast and to choose the most suitable
      expander for placement on the side to be reconstructed. METHODS: A retrospective
      study investigated 60 patients submitted to breast reconstruction between October
      2005 and January 2008. The study analyzed the characteristics of the healthy
      breast (e.g., volume, ptosis), which is treated in the first part of the first
      operation. These characteristics are used later as a model for reconstructing the
      mastectomy side. The most adequate technique for remodeling the healthy breast
      based on its characteristics is indicated, as well as techniques not recommended
      for obtaining the desired symmetry. RESULTS: This study aimed to determine the
      basis for selecting the most appropriate technique to use in managing the healthy
      breast and obtaining the most aesthetic result in breast reconstruction. The
      healthy breast analysis allows an algorithm of indications to be elaborated based
      on the volume and degree of ptosis exhibited by the healthy breast. The healthy
      breast should resemble the reconstructed breast with its anatomic implant. In
      this study, the technique used most often to remodel the healthy breast was
      reduction surgery with a superomedial pedicle, and glandular flap (autoimplant)
      (30%). The results were highly satisfactory for both the patient and the surgeon.
      CONCLUSIONS: Aesthetic remodeling of the healthy breast is the first surgical
      treatment in breast reconstruction in two stages using expanders and implants.
      The expander for reconstruction of the other breast then is selected according to
      the measurements of the healthy modified breast. This reproducible and simple
      model of breast reconstruction, with its detailed preoperative plan, allows
      clinicians to obtain a good aesthetic result for breast reconstruction patients.

PMID- 19156460
TI  - Breast cancer following augmentation mammaplasty with polyacrylamide hydrogel
      (PAAG) injection.
AB  - Polyacrylamide hydrogel (PAAG) as an implanted material for augmentation
      mammaplasty has been used for years in China. Many kinds of complications
      associated with PAAG use have been reported in the clinical literature. This
      report presents two cases of breast cancer occurring after injection of PAAG in
      augmented breasts. The delayed diagnosis and more aggressive disease due to PAAG
      injection should be cause for concern. It is very important to detect breast
      cancer early when it is covered by the induration of the injected gel and
      inflammation reaction after PAAG injection. PAAG injection for augmentation
      mammaplasty may affect the outcome of breast cancer diagnosis and prognosis.

PMID- 19156461
TI  - Expanded median forehead flap and abbe flap for nasal and upper lip
      reconstruction after complications of polymethylmethacrylate.
AB  - Despite the benefits from the minimally invasive technique, complications may
      occur, raising doubts about the safety of polymethylmethacrylate as an injectable
      filler material. The authors report their treatment of a patient from another
      institution with necrosis involving full-thickness nasal skin and upper lip after
      injection of polymethylmethacrylate in the nasolabial folds and nose for
      augmentation. An expanded median forehead flap was used to reconstruct the nose,
      and an Abbe flap was used for the upper lip. The flaps and the skin expander
      allowed reconstruction with correct texture, color, and dimensions, producing a
      good aesthetic and functional outcome.

PMID- 19156462
TI  - Neuropathy after herniorrhaphy: indication for surgical treatment and outcome.
AB  - BACKGROUND: Chronic neuropathy after hernia repair is a neglected problem as very
      few patients are referred for surgical treatment. The aim of the present study
      was to assess the outcome of standardized surgical revision for neuropathic pain
      after hernia repair. METHODS: In a prospective cohort study we evaluated all
      patients admitted to our tertiary referral center for surgical treatment of
      persistent neuropathic pain after primary herniorrhaphy between 2001 and 2006.
      Diagnosis of neuropathic pain was based on clinical findings and a positive
      Tinel's sign. Postoperative pain was evaluated by a visual analogue scale (VAS)
      and a pain questionnaire up to 12 months after revision surgery. RESULTS: Forty
      three consecutive patients (39 male, median age 35 years) underwent surgical
      revision, mesh removal, and radical neurectomy. The median operative time was 58
      min (range: 45-95 min). Histological examination revealed nerve entrapment,
      complete transection, or traumatic neuroma in all patients. The ilioinguinal
      nerve was affected in 35 patients (81%); the iliohypogastric nerve, in 10
      patients (23%). Overall pain (median VAS) decreased permanently after surgery
      within a follow-up period of 12 months (preoperative 74 [range: 53-87] months
      versus 0 [range: 0-34] months; p<0.0001). CONCLUSIONS: The results of this cohort
      study suggest that surgical mesh removal with ilioinguinal and iliohypogastric
      neurectomy is a successful treatment in patients with neuropathic pain after
      hernia repair.

PMID- 19156463
TI  - Does portal-superior mesenteric vein invasion still indicate irresectability for
      pancreatic carcinoma?
AB  - BACKGROUND: Pancreatic carcinoma frequently infiltrates the portal vein or the
      superior mesenteric vein; pancreatectomy combined with portal vein/superior
      mesenteric vein resection represents a potentially curative treatment in these
      cases but is still a controversial procedure. METHODS: After performing a
      computerized Medline search, 12 series published during the last 8 years were
      selected, enrolling 399 patients who underwent pancreatectomy combined with
      portal vein/superior mesenteric vein resection for pancreatic carcinoma. Data
      were examined for information about indications, operation, adjuvant therapies,
      histopathology of resected specimens, perioperative results, and survival. Also,
      previous literature regarding the issue was extensively reviewed. RESULTS:
      Operative mortality and postoperative complication rates ranged from 0 to 7.7%
      and 16.7% to 54%, respectively. Median survival varied from 13 to 22 months; 5
      year survival rate ranged from 9% to 18%. CONCLUSIONS: The current literature
      suggests that portal vein/superior mesenteric vein resection combined with
      pancreatectomy is a safe and feasible procedure that increases the number of
      patients who undergo curative resection and, therefore, provides important
      survival benefits to selected groups of patients. This procedure should always be
      considered in case of suspected tumor infiltration of portal/superior mesenteric
      vein to achieve clear resection margins, in the absence of other
      contraindications for resection.

PMID- 19156464
TI  - Bevacizumab-related surgical site complication despite primary tumor resection in
      colorectal cancer patients.
AB  - BACKGROUND: Combining conventional systemic chemotherapy with the angiogenesis
      inhibitor bevacizumab is now recommended as a first treatment for metastatic
      colorectal neoplasms. The risk for short-term postoperative complications related
      to bevacizumab has been assessed. Late postoperative complications related to
      bevacizumab have also been suggested by preliminary reports. METHODS: We reviewed
      a cohort of 142 patients with previous surgery for primary colonic or rectal
      tumor and without evidence of local recurrence, receiving bevacizumab for
      metastatic disease. RESULTS: Four patients experienced a late surgical site
      complication related to bevacizumab. Common features were rectal location, low
      anastomosis, and preoperative irradiation. Combining these three factors, the
      risk of a bevacizumab-related complication was 4 in 27 (14.8%); if previous
      history of postoperative leakage was reported, the risk was raised to 2 in 4. No
      complications occurred in colonic location or the non-irradiated patients. The
      mechanism of these complications could be ischemic lesion in post-irradiated
      tissues involving anastomoses. CONCLUSION: We conclude that angiogenesis
      inhibitors should be carefully considered for patients having low colorectal
      anastomosis and previous irradiation.

PMID- 19156465
TI  - Dislocation of the carpometacarpal joint of the thumb associated with trapezium
      and Bennett's fractures.
AB  - We report a case of a 30-year-old man with a carpometacarpal joint dislocation of
      the thumb associated with trapezium and Bennett's fractures. This combined injury
      pattern appears to be very rare. Since, to our knowledge a similar case was not
      found in the literature. The lesion was managed with closed reduction and
      percutaneous pinning, resulting in good functional outcome.

PMID- 19156466
TI  - Future of the US healthcare system and the effects on the practice of hand
      surgery.
AB  - The multitier healthcare system of the USA has several major flaws. High costs
      and uncertain quality of care indicate that this system is no longer practical.
      Several improvement initiatives, such as the Oregon Health Plan, Leapfrog, Lean
      Manufacturing, and Pay-for-Performance have been implemented into the current
      system. All of these quality improvement models are being experimented in a
      limited fashion and do not address the biggest problem in the US healthcare,
      inequality of care. There is now increasing support for a universal health
      coverage model as an ethically sound and just way to decrease health disparities
      in the USA. The current quality initiatives as well as an adoption of universal
      coverage appear to be the best way to improve quality of care, reduce cost, and
      increase equality in healthcare. These initiatives may have considerable effects
      on the practice of hand surgery in the near future, and thus, it is important for
      the field of hand surgery to become more engaged in advocacy and public policy
      arena. The purpose of this paper is to examine the current problems in the US
      healthcare system and to evaluate potential solutions that will enhance quality
      while simultaneously curbing the unchecked increase in healthcare expenditure.

PMID- 19156467
TI  - Identifying patients with post-discharge care problems using an interactive voice
      response system.
AB  - INTRODUCTION: Adverse events (AEs) are poor outcomes caused by medical care. They
      occur in 20% of medical patients following hospital discharge. We designed an
      interactive voice response system (IVRS) with the intent of identifying patients
      who might be experiencing an AE following discharge or were at risk of developing
      one. OBJECTIVES: We determined the proportion of post-discharge patients
      requiring an intervention after identifying potential problems using the IVRS,
      the relationship between IVRS responses and AE occurrence, and patients' opinions
      of the IVRS call. METHODS: We studied patients discharged from the general
      medical service of an academic hospital. The IVRS called patients 2 days post
      discharge and asked three questions to determine the need for nurse follow-up. We
      contacted patients 30 days later to elicit AE status and perceptions of the IVRS.
      RESULTS: Our cohort consisted of 270 elderly patients [median 64 years (IQR 50
      76)] with multiple co-morbidities. Responses to the IVRS identified 57 patients
      (21%, 95% CI 17%-27%) for follow-up. When contacted by a nurse, 25 patients (9%,
      95% CI 6%-13%) actually required an intervention. At 30-day follow-up, AEs
      occurred in 33 patients (12%, 95% CI 8%-17%). Only three AEs (9%) were identified
      by the IVRS; the remainder occurred before or after the IVRS call. Patients
      remembering the IVRS call found it easy to use (97%), and a minority would prefer
      a person to call (8%). CONCLUSION: An IVRS-based method of monitoring was
      acceptable to patients and identified a significant proportion requiring changes
      in management. However, the method identified only a minority of AEs. To have a
      significant improvement in care, this method will need to be combined with other
      interventions.

PMID- 19156468
TI  - Trends in primary care clinician perceptions of a new electronic health record.
AB  - BACKGROUND: Clinician perceptions of a newly implemented electronic health record
      play an important role in its success or failure. OBJECTIVE: To measure changes
      in primary care clinician attitudes toward an electronic health record during the
      first year following implementation. DESIGN: Longitudinal survey. PARTICIPANTS:
      86 primary care clinicians surveyed between December 2006 and January 2008.
      MEASUREMENTS: Perceived impact on overall quality of care, patient safety,
      communication, and efficiency at 1, 3, 6, and 12 months following implementation.
      RESULTS: Response rates for months 1, 3, 6, and 12 were 92%, 95%, 90%, and 82%,
      respectively. The proportion of clinicians agreeing that the EHR improved the
      overall quality of care (63% to 86%; p < 0.001), reduced medication-related
      errors (72% to 81%; p = 0.03), improved follow-up of test results (62% to 87%; p
      < 0.001), and improved communication among clinicians (72% to 93%; p < 0.001)
      increased from month 1 to month 12. During the same time period, a decreasing
      proportion of clinicians agreed that the EHR reduced the quality of patient
      interactions (49% to 33%; p = 0.001), resulted in longer patient visits (68% to
      51%; p = 0.001), and increased time spent on medical documentation (78% to 68%; p
      = 0.006). Significant improvements in perceptions related to test result follow
      up were first detected at 6 months, while those related to overall quality,
      efficiency, and communication were first identified at 12 months. CONCLUSIONS:
      Primary care clinicians report increasingly positive perceptions of a new
      electronic health record within 1 year of implementation across a spectrum of
      domains of care.

PMID- 19156469
TI  - Resident self-assessment and self-reflection: University of Wisconsin-Madison's
      Five-Year Study.
AB  - BACKGROUND: Chart review represents a critical cornerstone for practice-based
      learning and improvement in our internal medicine residency program. OBJECTIVE:
      To document residents' performance monitoring and improvement skills in their
      continuity clinics, their satisfaction with practice-based learning and
      improvement, and their ability to self-reflect on their performance. DESIGN:
      Retrospective longitudinal design with repeated measures. PARTICIPANTS: Eighty
      Internal Medicine residents abstracted data for 3 consecutive years from the
      medical records of their 4,390 patients in the University of Wisconsin-Madison
      (UW) Hospital and Clinics and William S. Middleton Veterans Administration (VA)
      outpatient clinics. MEASUREMENT: Logistic modeling was used to determine the
      effect of postgraduate year, resident sex, graduation cohort, and clinic setting
      on residents' "compliance rate" on 17 nationally recognized health screening and
      chronic disease management parameters from 2003 to 2007. RESULTS: Residents'
      adherence to national preventive and chronic disease standards increased
      significantly from intern to subsequent years for administering immunizations,
      screening for diabetes, cholesterol, cancer, and behavioral risks, and for
      management of diabetes. Of the residents, 92% found the chart review exercise
      beneficial, with 63% reporting gains in understanding about their medical
      practices, 26% reflecting on specific gaps in their practices, and 8% taking
      critical action to improve their patient outcomes. CONCLUSIONS: This paper
      provides support for the feasibility and practicality of this limited-cost method
      of chart review. It also directs our residency program's attention in the
      continuity clinic to a key area important to internal medicine training programs
      by highlighting the potential benefit of enhancing residents' self-reflection
      skills.

PMID- 19156470
TI  - Comparing care for breast cancer survivors to non-cancer controls: a five-year
      longitudinal study.
AB  - BACKGROUND: Deficiencies in care for cancer survivors may result from unclear
      roles for primary care providers (PCPs) and oncology specialists in follow-up.
      OBJECTIVES: To compare cancer survivors' care to non-cancer controls. DESIGN:
      Retrospective, longitudinal, controlled study starting 366 days post-diagnosis.
      SUBJECTS: Stage 1-3 breast cancer survivors age 65+ diagnosed in 1998 (n = 1961)
      and matched non-cancer controls (n = 1961). MEASUREMENTS: Using the SEER-Medicare
      database, we examined the number of visits to PCPs, oncology specialists, and
      other physicians; receipt of influenza vaccination, cholesterol screening,
      colorectal cancer screening, bone densitometry, and mammography; and whether care
      receipt was associated with physician mix visited. RESULTS: Survivors were
      consistently less likely to receive influenza vaccination, cholesterol screening,
      colorectal cancer screening, and bone densitometry but more likely to receive
      mammograms than controls (all p < 0.05). Over time, colorectal cancer screening
      and mammography decreased and influenza vaccination increased for both groups
      (all p < 0.0001). Trends over time in care receipt were similar for survivors and
      controls. In Year 1, survivors had more visits to PCPs but fewer visits to other
      physicians than controls (both p < 0.05). Over time, survivors' visits to PCPs
      and other physicians increased and to oncology specialists decreased (all p <
      0.0001). Controls' visits to PCPs increased (p < 0.0001) faster than survivors'
      (p = 0.003). Controls' visits to other physicians increased (p < 0.0001) at a
      rate similar to survivors. Survivors who visited both a PCP and oncology
      specialist were most likely to receive each service. CONCLUSIONS: Better
      coordination between PCPs and oncology specialists may improve care for older
      breast cancer survivors.

PMID- 19156471
TI  - Losing faith and using faith: older African Americans discuss spirituality,
      religious activities, and depression.
AB  - BACKGROUND AND OBJECTIVES: Older African Americans are often under diagnosed and
      under treated for depression. Given that older African Americans are more likely
      than whites to identify spirituality as important in depression care, we sought
      to understand how spirituality may play a role in the way they conceptualize and
      deal with depression in order to inform possible interventions aimed at improving
      the acceptability and effectiveness of depression treatment. DESIGN: Cross
      sectional qualitative interview study of older African American primary care
      patients. PARTICIPANTS AND SETTING: Forty-seven older African American patients
      recruited from primary care practices in the Baltimore, MD area, interviewed in
      their homes. MEASUREMENTS: Semi-structured interviews lasting approximately 60
      minutes. Interviews were transcribed and themes related to spirituality in the
      context of discussing depression were identified using a grounded-theory
      approach. MAIN RESULTS: Participants in this study held a faith-based explanatory
      model of depression with a particular emphasis on the cause of depression and
      what to do about it. Specifically, participants described depression as being due
      to a "loss of faith" and faith and spiritual/religious activities were thought to
      be empowering in the way they can work together with medical treatments to
      provide the strength for healing to occur. CONCLUSIONS: The older African
      Americans in this study described an intrinsically spiritual explanatory model of
      depression. Addressing spirituality in the clinical encounter may lead to
      improved detection of depression and treatments that are more congruent with
      patient's beliefs and values.

PMID- 19156472
TI  - Factors associated with the use of preventive care for contrast-induced acute
      kidney injury.
AB  - BACKGROUND: The factors that affect the implementation of preventive care for
      contrast-induced acute kidney injury (CIAKI) are unknown. OBJECTIVE: To assess
      patient and provider factors associated with the use of preventive care for
      CIAKI. DESIGN: Prospective cohort study. PARTICIPANTS: Patients with kidney
      disease undergoing procedures with intravascular iodinated radiocontrast.
      MEASUREMENTS: We recorded the use of preventive care defined as the
      administration of: (1) pre- and post-procedure isotonic intravenous (IV) fluid,
      (2) N-acetylcysteine, and (3) iso-osmolal radiocontrast. We surveyed patients'
      providers to assess their knowledge, experience, and training on CIAKI and used
      multiple logistic regression to assess the independent associations of patient
      and provider factors with the use of these preventive interventions. RESULTS: We
      enrolled 660 patients and 87 providers. Patient factors associated with use of IV
      fluid and N-acetylcysteine were higher baseline serum creatinine (OR 1.5 and 5.0,
      p < 0.05) and inpatient status (OR 3.0 and 6.3, p < 0.05), while higher baseline
      serum creatinine was associated with the use of iso-osmolal contrast (OR = 13.4,
      p < 0.01). The primary provider characteristics associated with the use of IV
      fluid and N-acetylcysteine were a greater degree of prior training on CIAKI (OR
      1.9 and 2.8, p < 0.05) and higher number of prior patients with CIAKI (OR 2.7 and
      2.6, p < 0.05). CONCLUSIONS: Patient baseline kidney function and provider
      training and experience with CIAKI are independently associated with the use of
      preventive care. Efforts to increase and intensify the training providers receive
      on CIAKI may help decrease the incidence of this costly iatrogenic condition.

PMID- 19156473
TI  - Mode of lymphadenectomy and surgical outcome of upper thoracic esophageal
      squamous cell carcinoma.
AB  - INTRODUCTION: Only a few studies have evaluated the impact of clinicopathological
      variables and cervical lymphadenectomy on survival in patients with upper
      thoracic esophageal squamous cell carcinoma (SCC). MATERIAL AND METHODS: From
      1960 to 2005, a total of 167 consecutive patients with upper thoracic esophageal
      SCC underwent esophagectomy. Of these patients, 108 underwent surgery between
      1960 and 1989 and 59 between 1990 and 2005. A total of 65 patients were treated
      with cervical lymphadenectomy. Univariate and multivariate analyses were
      performed to evaluate the impact of clinicopathological variables on surgical
      outcome and possible predictors for cervical lymph node metastasis. RESULTS AND
      DISCUSSION: The overall 5-year survival of the later period was significantly
      better than the former period (43% vs 13%, p < 0.01). Based on Cox's proportional
      hazards model, T3/T4 tumors, thoracic or abdominal node metastasis, venous
      invasion, residual cancer, absence of cervical lymphadenectomy, and hospital
      morbidity were independent risk factors for reduced survival in patients with
      upper thoracic esophageal SCC. A total of 31 (48%) of 65 patients who underwent
      cervical lymphadenectomy showed positive nodes in cervical field. CONCLUSION:
      Based on logistic regression analysis, T3/T4 tumors and recurrent nerve node
      metastasis were possible risk factors for cervical node metastasis.

PMID- 19156474
TI  - Reduced cerebellar inhibition in migraine with aura: a TMS study.
AB  - Subtle clinical cerebellar alterations have been found in migraine. Moreover,
      abnormalities in visual and motor cortex excitability consistent with a lack of
      inhibitory efficiency have been described in migraine, and it is known that
      cerebellum exerts an inhibitory control on cerebral cortex. Here, we investigated
      if impairment of cerebellar activity on motor cortex, i.e. reduced inhibitory
      control, can be found in migraine. Ten migraineurs with aura and seven healthy
      controls underwent a transcranial magnetic stimulation (TMS) protocol to
      investigate the cerebellar inhibitory drive on motor cortex: a conditioning pulse
      on right cerebellar cortex was delivered 5, 7, 10, 15 ms before a test stimulus
      (TS) on contralateral motor cortex. The cerebellar conditioning stimulus inhibits
      the size of the motor-evoked potential (MEP) produced by the TS alone by
      approximately 30-50%. Amplitude of MEP to TS alone showed no significant
      difference between patients and controls. Cerebellar conditioning TMS showed a
      significant deficit of cerebellar inhibition in migraine patients as compared to
      controls at all interstimulus intervals (5-15 ms) tested. Cerebellar inhibition
      is reduced in migraineurs. This could account, at least in part, for the reduced
      inhibitory efficiency previously showed in cerebral cortex of these patients.

PMID- 19156475
TI  - Association between anxiety disorder and the extent of ischemia observed in
      cardiac syndrome X.
AB  - BACKGROUND: A possible link between the heart and brain has been reported for
      cardiac syndrome X. Anxiety disorder could be a pathophysiological mechanism for
      this cardiac chest pain. To the authors' knowledge, a quantitative analysis
      correlating anxiety with the extent of ischemia has not been done. METHODS AND
      RESULTS: In this pilot study, we evaluated 20 patients with typical chest pain
      and completely normal coronary angiograms. These patients were screened with the
      State Scale and Trait Scale of the State-Trait Anxiety Inventory (STAI). All
      patients underwent myocardial perfusion scintigraphic imaging. The scintigrams
      were scored by three experienced readers having no knowledge of the STAI
      screening results. Patients with a low trait anxiety had significantly less
      ischemic segments on the myocardial perfusion imaging than patients with a high
      trait anxiety (1.8 +/- 1.9 vs 3.5 +/- 0.6, P < .05). For state anxiety, no
      significant differences could be found. CONCLUSION: Cardiac syndrome X patients
      with high trait anxiety are at risk of having more ischemia.

PMID- 19156476
TI  - An anomalous RCA with ischemia on myocardial perfusion imaging.

PMID- 19156477
TI  - Validation of attenuation correction using transmission truncation compensation
      with a small field of view dedicated cardiac SPECT camera system.
AB  - BACKGROUND: Although attenuation correction (AC) has been successfully applied to
      large field of view (LFOV) cameras, applicability to small field of view (SFOV)
      cameras is a concern due to truncation. This study compared perfusion images
      between a LFOV and SFOV camera with truncation compensation, using the same AC
      solution. METHODS AND RESULTS: Seventy-eight clinically referred patients
      underwent rest-stress single-photon emission computed tomography (SPECT) using
      both a SFOV and LFOV camera in a randomized sequence. Blinded images were
      interpreted by a consensus of three experienced readers. The percentage of normal
      images for SFOV and LFOV was significantly higher with than without AC (72% vs
      44% and 72% vs 49%, both P < .001). Interpretive agreement between cameras was
      better with than without AC (kappa = 0.736 to 0.847 vs 0.545 to 0.774).
      Correlation for the summed stress score was higher with than without AC (r (2) =
      0.892 vs 0.851, both P < 0.001) while Bland Altman analysis demonstrated narrower
      limits with than without AC (4.0 to -4.3 vs 5.9 to -5.6). CONCLUSION: Attenuation
      correction using truncation compensation with a SFOV camera yields similar
      results to a LFOV camera. The higher interpretive agreement between cameras after
      attenuation correction suggests that such images are preferable to non
      attenuation-corrected images.

PMID- 19156478
TI  - Diagnostic performance of fusion of myocardial perfusion imaging (MPI) and
      computed tomography coronary angiography.
AB  - BACKGROUND: We evaluated the incremental diagnostic value of fusion images of
      coronary computed tomography angiography (CTA) and myocardial perfusion imaging
      (MPI) over MPI alone or MPI and CTA side-by-side to identify obstructive coronary
      artery disease (CAD > 50% stenosis) using invasive coronary angiography (ICA) as
      the gold standard. METHODS: 50 subjects (36 men; 56 +/- 11 years old) underwent
      rest-stress MPI and CTA within 12-26 days of each other. CTAs were performed with
      multi-detector CT-scanners (31 on 64-slice; and 19 on 16-slice). 37 patients
      underwent ICA while 13 subjects did not because of low (<5%) pre-test likelihood
      (LLK) of disease. Three blinded readers scored the images in sequential sessions
      using (1) MPI alone (2) MPI and CTA side-by-side, (3) fused CTA/MPI images.
      RESULTS: One or more critical stenoses during ICA were found in 28 patients and
      non-critical stenoses were found in 9 patients. MPI, side-by-side MPI-CTA, and
      fused CTA/MPI showed the same normalcy rate (NR:13/13) in LLK subjects. The
      fusion technique performed better than MPI and MPI and CTA side-by-side for the
      presence of CAD in any vessel (overall area under the curve (AUC) for fused
      images: 0.89; P = .005 vs MPI, P = .04 vs side-by-side MPI-CTA) and for
      localization of CAD to the left anterior descending coronary artery (AUC: 0.82, P
      < .001 vs MPI; P = .007 vs side-by-side MPI-CTA). There was a non-significant
      trend for better detection of multi-vessel disease with fusion. CONCLUSIONS:
      Using ICA as the gold standard, fusion imaging provided incremental diagnostic
      information compared to MPI alone or side-by-side MPI-CTA for the diagnosis of
      obstructive CAD and for localization of CAD to the left anterior descending
      coronary artery.

PMID- 19156479
TI  - Persisting myocardial sympathetic dysfunction in takotsubo cardiomyopathy.

PMID- 19156480
TI  - Threshold, incidence, and predictors of prognostically high-risk silent ischemia
      in asymptomatic patients without prior diagnosis of coronary artery disease.
AB  - BACKGROUND: Little is known about incidence, threshold, and predictors of
      prognostically relevant silent ischemia (SI). The aim was to study these three
      aspects of silent coronary artery disease (CAD). METHODS: In total, 3,664
      consecutive asymptomatic patients without prior diagnosis of CAD undergoing
      myocardial perfusion SPECT (MPS) were evaluated and followed-up > or = 1 year for
      Events (HE): cardiac death or myocardial infarction. MPS was interpreted using a
      20 segment model to define summed stress, rest, and difference scores (the extent
      of % myocardium ischemic was derived). Prognostic high-risk ischemia was defined
      as ischemia consistent with a HE rate > or = 3%. RESULTS: Overall, > or = 7.5%
      myocardium ischemic was consistent with high risk. Twenty-one and six percent of
      patients had ischemia and high-risk ischemia, respectively. Patients with high
      risk ischemia had a worse prognosis than patients with less SI, HE rate of 3.1
      and 0.4%, respectively, (P = .0001). Sex, age, diabetes, hypertension, abnormal
      resting ECG, angina, peak heart rate, blood pressure during treadmill testing, ST
      depression, and Duke treadmill score were independent predictors of relevant SI.
      CONCLUSIONS: In total, > or = 7.5% myocardium ischemic revealed to be consistent
      with high risk. Six percent of patients had evidence of high-risk SI. Diagnostic
      scores are provided to most likely identify patients with high-risk SI.

PMID- 19156481
TI  - Amino acid requirements in humans: with a special emphasis on the metabolic
      availability of amino acids.
AB  - Due to advances made in the development of stable isotope based carbon oxidation
      methods, the determination of amino acid requirements in humans has been an
      active area of research for the past 2 decades. The indicator amino acid
      oxidation (IAAO) method developed in our laboratory for humans has been
      systematically applied to determine almost all indispensable amino acid
      requirements in adult humans. Nutritional application of experimentally derived
      amino acid requirement estimates depends upon the capacity of food proteins to
      meet the amino acid requirements in humans. Therefore, there is a need to know
      the proportion of dietary amino acids which are bioavailable, or metabolically
      available to the body for protein synthesis following digestion and absorption.
      Although this concept is widely applied in animal nutrition, it has not been
      applied to human nutrition due to lack of data. We developed a new in vivo method
      in growing pigs to identify the metabolic availability of amino acids in foods
      using the IAAO concept. This metabolic availability method has recently been
      adapted for use in humans. As this newly developed IAAO based method to determine
      metabolic availability of amino acids in foods is suitable for rapid and routine
      analysis in humans, it is a major step forward in defining the protein quality of
      food sources and integrating amino acid requirement data with dietary amino acid
      availability of foods.

PMID- 19156482
TI  - Papaya latex enzymes capable of detoxification of gliadin.
AB  - Assay of fractions obtained from ion exchange chromatography of papaya latex on
      CM Sephadex-C50, size exclusion chromatography on Sephacryl S-300 and size
      exclusion HPLC have provided an insight into the relative contributions of the
      gluten-detoxifying enzymes present. This outcome has been achieved by the use of
      the above chromatographic techniques, coupled with assays of lysosomal activity,
      protease activity using benzylarginine ethyl ester (BAEE) as substrate, prolyl
      endopeptidase (PEP) using glycylprolylnitroanilide and a prolidase assay using
      acetylprolylglycine. These procedures have shown that the activity in papaya
      latex is due largely to caricain and to a lesser extent, chymopapain and
      glutamine cyclotransferase. The presence of caricain and these other enzymes was
      confirmed by mass spectrometry of trypsin digests of the most active fraction
      obtained by CM Sephadex-C50 chromatography and size exclusion HPLC. Fractions
      rich in caricain would be suitable for enzyme therapy in gluten intolerance and
      appear to have synergistic action with porcine intestinal extracts.

PMID- 19156484
TI  - Nosocomial ventriculitis and meningitis in neurocritical care patients.
AB  - BACKGROUND: External ventricular drainage (EVD) is frequently necessary in
      neurological and neurosurgical intensive care patients. A major complication of
      this procedure is an EVD-related venticulitis or meningitis. The purpose of this
      review is (1) to address the magnitude of the problem in the neurocritical care
      patient population, (2) to discuss the difficulties in providing an appropriate
      and timely diagnosis of this disease entity and (3) to propose an algorithm for
      both rapid diagnosis and appropriate therapy. METHODS: A MEDLINE literature
      search was carried out for studies from January 1990 through March 2008 reporting
      on ventriculostomy, EVD-related central nervous system infections, in particular
      ventriculitis and meningitis. RESULTS: EVD-related ventriculitis is a serious
      nosocomial complication in the neurocritical care setting where EVD catheters are
      frequently used for the management of elevated ICP secondary to acute
      hydrocephalus primarily caused by subarachnoid and intraventricular hemorrhage or
      traumatic brain injury. Infection rate is high with reported incidences in the
      range of 5 % up to more than 20 %. Predisposing factors for infection are non
      adherence to rigid insertion and maintenance protocols, leakage of cerebrospinal
      fluid (CSF), catheter irrigation and the frequency of EVD manipulation. Diagnosis
      is frequently impaired either by the presence of systemic inflammation due to the
      primary disease or because the hemorrhagic CSF itself may cause an inflammatory
      reaction. Furthermore, the most common pathogens involved in EVD-related
      infections, i. e., staphylococci, initially provoke only a mild inflammatory
      response in the CSF and therefore patients rarely present with clear-cut clinical
      signs indicating severe central nervous system infection, in particular,
      ventriculitis. CONCLUSION: Nosocomial EVD-related ventriculitis is a significant
      cause of morbidity and mortality in critically ill neurological patients. Rapid
      diagnosis and prompt initiation of appropriate antimicrobial therapy is needed. A
      stepwise algorithm for the management of EVD-related ventriculitis is proposed.

PMID- 19156485
TI  - A clinically isolated syndrome: a challenging entity: multiple sclerosis or
      collagen tissue disorders: clues for differentiation.
AB  - Acute isolated neurological syndromes, such as optic neuropathy or transverse
      myelopathy, may cause diagnostic problems since they can be the first
      presentations of a number of diseases such as multiple sclerosis (MS) and
      collageneous tissue disorders. In the present study, particular systemic lupus
      erythematosus (SLE) and primary Sjogren syndrome (pSS) patients, who were
      followed up with the initial diagnosis of possible MS with no evidence of
      collagen tissue disorders for several years, are described. Five patients with
      the final diagnosis of SLE and five pSS patients are evaluated with their
      neurologic, systemic and radiologic findings.Over several years, all developed
      some systemic symptoms like arthritis, arthralgia, headache, dry mouth and eyes
      unexpected in MS. During the regular and close follow-up laboratory evaluations
      of vasculitic markers revealed positivity, leading to the final definite
      diagnosis of SLE or pSS. Patients with atypical neurological presentation of MS,
      a relapsing remitting clinical profile, or lack of response to the regular MS
      treatment should be evaluated for the presence of a connective tissue disease.
      Various laboratory tests, such as cerebrospinal fluid findings, autoantibodies
      profile, markers, cranial and spinal magnetic resonance imaging, can be helpful
      for the differential diagnosis. Lack of response to the regular multiple
      sclerosis treatment, even increasing rate of relapses can force the clinician for
      the differential diagnosis. In particular cases an accurate diagnosis can only be
      made after close follow-up.

PMID- 19156486
TI  - Risk vs benefit of anti-thrombotic therapy in ischaemic stroke patients with
      cerebral microbleeds.
AB  - BACKGROUND: Retrospective studies suggested that cerebral microbleeds (MB) on
      magnetic resonance images (MRI) increase risk of intracerebral haemorrhage (ICH).
      OBJECTIVE: To compare the benefit of anti-thrombotic agents in stroke prevention
      (absolute risk reduction 2.49 -6 %) versus risk of ICH in ischaemic stroke
      patients with MB. MATERIALS AND METHODS: We prospectively studied patients
      admitted consecutively for acute ischaemic stroke between 1999 and 2004. MB on
      MRI were documented. Primary end points were subsequent ICH, recurrent cerebral
      infarct (CI) and mortality. RESULTS: A total of 908 patients were recruited. MB
      were identified in 252 (27.8 %) patients. Mean follow-up period was 26.6 +/- 15.4
      months. Risk of subsequent ICH increased significantly with quantity of MB: 0.6 %
      (no MB), 1.9 % (1 MB), 4.6 % (2-4 MB) and 7.6 % (>or= 5 MB) (p < 0.001). There
      was also a significant increase in mortality from ICH: 0.6 %, 0.9 %, 1.5 % and
      3.8 % respectively (p = 0.054). Rate of recurrent CI was 9.6 %, 5.6 %, 21.5 % and
      15.2 % respectively (p = 0.226). Mortality from CI and myocardial infarction did
      not increased with quantity of MB. Survival analyses showed that age, presence of
      MB, mixed cortical-subcortical distribution of MB were independent predictors of
      subsequent ICH. CONCLUSION: Risk and mortality of ICH increased with quantity of
      MB. As tendency to recurrent CI exceed that of ICH, anti-thrombotic agents are
      still warranted. However, in patients with >or= 5 MB, the high risk and mortality
      of ICH seem to outweigh the modest benefit of antithrombotic agents. Extra
      precautions should be taken to minimize risk of ICH. Further studies in patients
      on Coumadin and assessment of functional outcome are warranted to support these
      preliminary findings.

PMID- 19156488
TI  - Depression in focal, segmental and generalized dystonia.
AB  - Dystonia causes body disfigurement in the majority of those affected. Our aim was
      to test the hypothesis that low self-esteem resulting from the sense of
      disfigurement is an important component of self-reported depression in focal,
      segmental and generalized dystonia. Questionnaires to assess self-reported
      depression, self-esteem, body concept, disfigurement, disability and quality of
      life were completed by 329 community based dystonia patients. Moderate to severe
      depression was reported by 30 %. Self-reported depression had a strong somatic
      component, but patients also showed a specific concern with self-image. Extent of
      dystonia, body parts affected and marital status influenced self-reported
      depression in dystonia. Self esteem, body concept, disfigurement and quality of
      life emerged as factors which accounted for the variance of self-reported
      depression in dystonia. These results suggest that in dystonia, disfigurement,
      negative body concept, low self-esteem, and the impact of the disease on quality
      of life make important contributions to depression. However, longitudinal
      followup is required to firmly establish the direction of causality between
      depression and these psychosocial variables in dystonia.

PMID- 19156487
TI  - Proteome-based identification of plasma proteins associated with hippocampal
      metabolism in early Alzheimer's disease.
AB  - BACKGROUND AND METHODS: There is an urgent need for peripheral surrogates of
      Alzheimer's disease (AD) that accurately reflect disease state and severity as
      well as correlate with key features of its neuropathology. The aim of this study
      was to identify plasma proteins associated with known in vivo markers of disease
      activity. In an earlier proteomic study of plasma, we discovered a panel of 15
      proteins that were differentially expressed in AD and further validated
      complement factor-H (CFH) and alpha-2-macroglobulin (A2M) as AD-specific plasma
      biomarkers. In the present study, we extended these findings by testing the
      associations of these plasma proteins with neuro-imaging measures of disease
      progression in AD. We combined (1)H-magnetic resonance spectroscopy of the
      hippocampus and MRI-based hippocampal volumetry with proteomic analysis of plasma
      in early AD and mild cognitive impairment (MCI) to achieve this goal. Using (1)H
      magnetic resonance spectroscopy, we derived estimates of the hippocampal
      metabolite ratio N-acetylaspartate/myo-inositol (NAA/mI), a biochemical measure
      that is associated with cognitive decline in early AD. We also undertook a
      proteomic analysis of plasma in these individuals using two-dimensional gel
      electrophoresis (2DGE). RESULTS: We observed that two plasma proteins previously
      shown to be differentially expressed in AD, complement factor-H (CFH) and alpha-2
      macroglobulin (A2M) showed significant positive correlations with hippocampal
      NAA/mI ratio in AD. CONCLUSIONS: The association of plasma CFH and A2M with
      hippocampal NAA/mI in this cohort of AD subjects suggests that these proteins may
      reflect disease progression in early AD. These findings warrant validation in
      large population-based datasets.

PMID- 19156489
TI  - Left ventricular long-axis function in myasthenia gravis.
AB  - Myasthenia gravis (MG) primarily affects skeletal muscles, but influence on
      cardiac function has been suggested. The aim of this study was to assess left
      ventricular long-axis function in MG patients compared to healthy controls, and
      to examine whether any MG-related heart involvement was influenced by the
      acetylcholine-esterase inhibitor pyridostigmine. We found that early diastolic
      atrioventricular-plane velocity and tissue Doppler peak systolic strain was lower
      in MG patients than in controls before pyridostigmine. The differences
      disappeared following administration of pyridostigmine. Also, tissue velocities
      at systole and early diastole tended to be lower in patients before
      pyridostigmine. In multivariate analyses adjusting for between-group differences
      in blood pressure, MG was no longer associated with lower longaxis function.
      Conventional echocardiographic measures of left ventricular diastolic and
      systolic function did not differ between groups. In conclusion, this study, using
      modern tissue Doppler imaging as well as conventional echocardiography, could not
      demonstrate definite MG-related cardiac involvement in a group of MG patients
      without known cardiac disease, but indicates that pyridostigmine-responsive MG
      related alterations in cardiac muscle function exist in MG patients.

PMID- 19156490
TI  - Basal ganglia volume and clinical correlates in 'preclinical' Huntington's
      disease.
AB  - OBJECTIVE: To establish differences in basal ganglia and thalamic volume between
      preclinical carriers and non-carriers of the Huntington's disease (HD) gene and
      to link the volume to motor, cognitive and behavioural characteristics in
      carriers. METHODS: Sixteen HD gene carriers without overt clinical motor signs
      and 14 non-gene carriers underwent clinical evaluation and a MRI scan. Volumes of
      the caudate nucleus, putamen, gobus pallidus and thalamus were measured using T1
      weighted MR images. Motor, cognitive and behavioural functioning was assessed
      using the Unified Huntington's Disease Rating Scale (UHDRS), cognitive testing
      and the Beck Depression Inventory (BDI-II). RESULTS: Volumes of the caudate
      nucleus, putamen and globus pallidus were significantly smaller in carriers than
      in non-carriers while no differences between groups were found on clinical
      evaluation. In gene carriers smaller globus pallidus volume was associated with
      more motor abnormalities. A smaller putamen volume correlated significantly with
      worse psychomotor function on the Symbol Digit Modalities Task and the Trail
      Making Test B. CONCLUSIONS: In line with previous research we demonstrated that
      basal ganglia abnormalities precede overt disease manifestation of HD. Besides we
      showed that smaller basal ganglia volumes are related to subtle motor
      abnormalities and worse psychomotor performance in gene carriers without clinical
      diagnosis. Motor and psychomotor measures may be suitable clinical markers in
      future neuroprotective trials when combined with volumetric imaging.

PMID- 19156493
TI  - Successful prophylactic treatment of chronic cluster headache with low-dose
      levomethadone.

PMID- 19156491
TI  - Telemedicine in acute stroke: remote video-examination compared to simple
      telephone consultation.
AB  - BACKGROUND: Telemedicine is increasingly being used in acute stroke care. Some of
      the first studies and network projects are already applying remote audiovisual
      communication for patient evaluation. Formerly the telephone was the method of
      choice to contact experts for case discussion. We compared remote video
      examination and telephone consultation in acute stroke care. METHODS: Two
      district hospitals were linked to stroke centers in Northern Bavaria. Patients
      with symptoms suggestive of an acute stroke were included. Remote video
      examination (RVE) was provided by live audiovisual communication and access to
      brain images; telephone consultation (TC) was done via standard telephone using a
      structured interview. There was a weekly rotation of the two methods. Demographic
      data and other data concerning process and quality of care as well as outcome 10
      days after stroke were recorded and compared between the two groups. RESULTS:
      Within the study period 151 consultations were made in acute stroke patients
      (mean age 66.8 years). 77 patients were seen by RVE and 74 by TC. Total
      examination times were 49.8 min for RVE and 27.2 min for TC (p < 0.01). Patients
      were more frequently transferred to the stroke center after TC consultation (9.1
      % vs. 14.9 %, p < 0.05) and had a higher mortality 10 days after stroke (6.8 %
      vs. 1.3 %, p < 0.05). Diagnosis made by TC had to be corrected more frequently
      (17.6 % vs. 7.1 %; p < 0.05). CONCLUSIONS: Creating a network improves stroke
      care by establishing cooperation between hospitals. Telephone consultation could
      be a simple method of telemedicine to support cooperation as it is easy and
      widely available. However, outcome parameters like mortality indicate that remote
      video examination is superior to TC. Therefore, full-scale audiovisual
      communication is recommended for remote consultation in acute stroke care.

PMID- 19156494
TI  - Churg Strauss syndrome presenting as acute neuropathy resembling Guillain Barre
      syndrome: case report.

PMID- 19156495
TI  - Chronic meningoencephalomyelitis due to Mycobacterium fortuitum in an
      immunocompetent patient.

PMID- 19156496
TI  - Glucose-6-phosphate dehydrogenase activity in Parkinson's disease.

PMID- 19156499
TI  - A new phenolic glycoside syringate from the bark of Juglans mandshurica MAXIM.
      var. sieboldiana MAKINO.
AB  - A new phenolic glycoside syringate, 4'-hydroxy-2',6'-dimethoxyphenol 1-O-beta-D: 
      (6-O-syringoyl) glucopyranoside (1), together with two known ones, 2'-hydroxy-4'
      methoxyphenol 1-O-beta-D: -(6-O-syringoyl) glucopyranoside (2) and 4'-hydroxy-2'
      methoxyphenol 1-O-beta-D: -(6-O-syringoyl) glucopyranoside (3), were isolated
      from the bark of Juglans mandshurica MAXIM. var. sieboldiana MAKINO. Their
      structures were established on the basis of spectral and chemical data.

PMID- 19156500
TI  - Pediatric post-transplant diffuse large B cell lymphoma after cardiac
      transplantation.
AB  - Post-transplant lymphoproliferative disorders (PTLDs) occur in 3.5-9% of patients
      after pediatric cardiac transplantation. Caution is needed when treating patients
      with PTLD because of the risk of allograft rejection frequently caused by
      withdrawal of immunosuppression. In this report, we describe a 47-month-old boy
      who developed PTLD as an ileocecal mass 29 months after cardiac transplantation.
      Immunosuppressive therapy with cyclosporine A (CyA) had been reduced due to an
      elevation of Epstein-Barr virus (EBV) titer for 8 months before development of
      PTLD. Histology of the tumor was diffuse large B cell lymphoma. EBV was detected
      by in situ hybridization assay. Cytogenetic analysis revealed t(8;14)(q24;q32)
      and Southern blot analysis detected a c-Myc rearrangement. He was treated with
      rituximab and combination chemotherapy with excellent response. CyA dose was
      maintained at reduced levels during chemotherapy and later minimized with
      introduction of everolimus. The child is free of both PTLD and allograft
      rejection 41 months after the diagnosis of PTLD.

PMID- 19156501
TI  - Immunoglobulin M 'Flare' after rituximab-associated acute tubular necrosis in
      Waldenstrom's macroglobulinemia.
AB  - Waldenstrom's macroglobulinemia (WM) is a low-grade lymphoplasmacytic lymphoma
      characterized by a circulating monoclonal IgM. Renal involvement in classical
      cases of WM is rare, and the pathological hallmark finding in the renal biopsy
      specimen is a thrombotic microangiopathy. We report the case of a 69-year-old man
      with the diagnosis of WM for 3 months before he presented with acute renal
      failure (ARF). A renal biopsy performed suggested the diagnosis of acute tubular
      necrosis. The diagnosis of ARF related to IgM flare after Rituximab therapy was
      made.

PMID- 19156502
TI  - Kinesin motor proteins as targets for cancer therapy.
AB  - The process of mitosis is a validated point of intervention in cancer therapy and
      a variety of anti-mitotic drugs are successfully being used in the clinic. To
      date, all approved antimitotics target the spindle microtubules, thus interfering
      with spindle dynamics, leading to mitotic arrest and apoptosis. While effective,
      these drugs are also associated with a variety of side effects, including
      neurotoxicity. In recent years, mitotic kinesins have attracted significant
      attention in the search for novel, alternative mitotic drug targets. Due to their
      specific function in mitosis, targeting these proteins creates an opportunity for
      the development of more selective antimitotics with an improved side effect
      profile. In addition, kinesin inhibitors may overcome resistance to microtubule
      targeting drugs. Drug discovery efforts in this area have initially focused on
      the plus-end directed kinesin spindle protein (KSP) and a variety of compounds
      are currently undergoing clinical testing.

PMID- 19156503
TI  - Centrosomes and cancer: how cancer cells divide with too many centrosomes.
AB  - Precise control of centrosome number is crucial for bipolar spindle assembly and
      accurate transmission of genetic material to daughter cells. Failure to properly
      control centrosome number results in supernumerary centrosomes, which are
      frequently found in cancer cells. This presents a paradox: during mitosis, cells
      with more than two centrosomes are prone to multipolar mitoses and cell death,
      however, cancer cells possessing extra centrosomes usually divide successfully.
      One mechanism frequently utilized by cancer cells to escape death caused by
      multipolar mitoses is the clustering of supernumerary centrosomes into bipolar
      arrays. An understanding of the molecular mechanisms by which cancer cells can
      suppress multipolar mitoses is beginning to emerge. Here, we review what's
      currently known about centrosome clustering mechanisms and discuss potential
      strategies to target these mechanisms for the selective killing of cancer cells.

PMID- 19156504
TI  - Controlled release of high molecular weight hyaluronic Acid from molecularly
      imprinted hydrogel contact lenses.
AB  - PURPOSE: Current dry eye treatment includes delivering comfort agents to the eye
      via drops, but low bioavailability and multiple administration continues to be a
      barrier to effective treatment. There exists a significant unmet need for devices
      to treat dry eye and for more comfortable contact lenses. METHODS: Using
      molecular imprinting strategies with an analysis of biology, we have rationally
      designed and synthesized hydrogel contact lenses that can release hyaluronic acid
      (HA) at a controlled rate. RESULTS: Delayed release characteristics were
      significantly improved through biomimetic imprinting, as multiple functional
      monomers provided non-covalent complexation points within nelfilcon A gels
      without altering structural, mechanical, or optical properties. The diffusion
      coefficient of 1.2 million Dalton HA was controlled by varying the number and
      variety of functional monomers (increasing the variety lowered the HA diffusion
      coefficient 1.5 times more than single functional monomers, and 1.6 times more
      than nelfilcon A alone). CONCLUSIONS: HA can be delivered from a daily disposable
      lens at a therapeutic rate of approximately 6 microg/h for 24 h. This is the
      first demonstration of imprinting a large molecular weight polymer within a
      hydrogel and the effect of imprinting on the reptation of the long chain
      macromolecule from the structure.

PMID- 19156505
TI  - A new probabilistic rule for drug-dug interaction prediction.
AB  - An innovative probabilistic rule is proposed to predict the clinical significance
      or clinical insignificance of DDI. This rule is coupled with a hierarchical
      Bayesian model approach to summarize substrate/inhibitor's PK models from
      multiple published resources. This approach incorporates between-subject and
      between-study variances into DDI prediction. Hence, it can predict both
      population-average and subject-specific AUCR. The clinically significant DDI,
      weak DDI, and clinically insignificant inhibitions are decided by the
      probabilities of predicted AUCR falling into three intervals, (-infinity, 1.25),
      (1.25, 2), and (2, infinity). The main advantage of this probabilistic rule to
      predict clinical significance of DDI over the deterministic rule is that the
      probabilistic rule considers the sample variability, and the decision is
      independent of sampling variation; while deterministic rule based decision will
      vary from sample to sample. The probabilistic rule proposed in this paper is best
      suited for the situation when in vivo PK studies and models are available for
      both the inhibitor and substrate. An early decision on clinically significant or
      clinically insignificant inhibition can avoid additional DDI studies.
      Ketoconazole and midazolam are used as an interaction pair to illustrate our
      idea. AUCR predictions incorporating between-subject variability always have
      greater variances than population-average AUCR predictions. A clinically
      insignificant AUCR at population-average level is not necessarily true when
      considering between-subject variability. Additional simulation studies suggest
      that predicted AUCRs highly depend on the interaction constant K(i) and dose
      combinations.

PMID- 19156506
TI  - Functional interpretations of sadness, stress and demoralization among an urban
      population of low-income mothers.
AB  - OBJECTIVES: We sought to understand how low-income urban mothers explain feelings
      of sadness, stress or demoralization in the context of their life experiences.
      METHODS: 28 in-depth qualitative interviews, constituting part of a community
      based participatory research (CBPR) project aimed at developing a culturally
      relevant, community-based intervention for maternal depression. Qualitative data
      validity was ensured through investigator and expert triangulation, and through
      member checking. RESULTS: The following themes emerged: (1) Informants spoke of
      wanting reprieves from chaos, and discussed this desire relative to wanting to be
      alone. By contrast, informants expressed loneliness not only in interpersonal
      terms, but also related to having problems that precluded future relationships,
      or feeling unique in experiencing an adversity. (2) Informants spoke of
      demoralization associated with feeling that their problems were externally
      imposed and therefore beyond their control, but spoke of empowerment associated
      with owning one's problems. (3) Informants discussed degrees of sadness in
      relation to their own abilities to adjust or modify their mood, or their ability
      to contain their feelings. CONCLUSIONS: Our data suggest that helping a mother
      find reprieves from chaos, increasing her perception of her own locus of control
      around externally imposed adversities, and empowering her to recognize and self
      manage her own feelings may constitute important elements of a culturally
      relevant, community-based intervention for depression.

PMID- 19156507
TI  - Correlates of pre-pregnancy physical inactivity: results from the pregnancy risk
      assessment monitoring system.
AB  - OBJECTIVES: Evaluate the prevalence of physical inactivity (no physical activity
      or exercise for 30 min or more at least one day per week) in the 3 months prior
      to pregnancy in a population-based sample of women and identify individual socio
      demographic, personal, health, and behavioral factors predictive of pre-pregnancy
      physical inactivity. METHODS: In this cross-sectional study, we used data from
      the Centers for Disease Control and Prevention's Pregnancy Risk Assessment
      Monitoring System to assess the prevalence of self-reported pre-pregnancy
      physical activity among 4,069 women who delivered a live birth in 2004 in Maine,
      North Carolina, or Washington State. We developed a predictive model by using a
      backward selection approach to building logistic regression models to identify
      independent predictors of physical inactivity in the 3 months prior to pregnancy
      among those women who did not meet national recommendations for physical activity
      (activity more than 5 days per week). RESULTS: Overall, the prevalence of pre
      pregnancy physical inactivity was 39.2%. Predictors of physical inactivity prior
      to pregnancy included higher or lower than normal pre-pregnancy body mass index,
      lower maternal education level, and a history of previous live births. Women with
      12 years of education were particularly likely to be inactive prior to pregnancy
      (prevalence odds ratio 1.81, 95% confidence interval 1.42, 2.32; compared to
      women with more than 12 years of education). CONCLUSIONS: Physical inactivity is
      common among women prior to pregnancy. Information on factors predictive of
      physical inactivity can be used in the development of clinical activities and
      public health interventions that aim to reduce the level of physical inactivity
      among women of reproductive age.

PMID- 19156508
TI  - Maternal socio-demographic factors influencing the initiation and exclusivity of
      breastfeeding in a Nigerian semi-urban setting.
AB  - BACKGROUND: The success of breastfeeding promotion is influenced by maternal
      factors. Therefore, it is vital to examine the influence of basic maternal
      demographic factors on breastfeeding practices. OBJECTIVE: To determine the
      influence of maternal socio-demographic factors on the initiation and exclusivity
      of breastfeeding. METHOD: A cross-sectional survey of mothers of children aged
      from 1 to 24 months attending a Nigerian Infant Welfare Clinic was conducted.
      Respondents were grouped according to age, parity, education, occupation, sites
      of antenatal care and delivery. These groups were compared for breastfeeding
      indices using bivariate and multivariate analysis. RESULTS: All the 262
      respondents breastfed their children. The exclusive breastfeeding rate was 33.3%
      for children aged 0-3 months, 22.2% for children aged 4-6 months and 19.4% for
      children aged 7-24 months at the time of the study. Significantly higher
      proportions of mothers with at least secondary education, clinic-based antenatal
      care and delivery in health facilities initiated breastfeeding within 1 h of
      birth, avoided pre-lacteal feeding and practiced exclusive breastfeeding for the
      first 6 months of life. Maternal age and parity did not confer any advantage on
      breastfeeding practices. Delivery of children outside health facilities strongly
      contributed to delayed initiation of breastfeeding (P < 0.001), pre-lacteal
      feeding (P = 0.003) and failure to breastfeed exclusively (P = 0.049). Maternal
      education below secondary level strongly contributed to pre-lacteal feeding (P =
      0.004) and failure to practice exclusive breastfeeding (P = 0.008). CONCLUSION:
      Low maternal education and non-utilization of orthodox obstetric facilities
      impairs early initiation and exclusivity of breastfeeding.

PMID- 19156509
TI  - Spike-time reliability of layered neural oscillator networks.
AB  - We study the reliability of layered networks of coupled "type I" neural
      oscillators in response to fluctuating input signals. Reliability means that a
      signal elicits essentially identical responses upon repeated presentations,
      regardless of the network's initial condition. We study reliability on two
      distinct scales: neuronal reliability, which concerns the repeatability of spike
      times of individual neurons embedded within a network, and pooled-response
      reliability, which concerns the repeatability of total synaptic outputs from a
      subpopulation of the neurons in a network. We find that neuronal reliability
      depends strongly both on the overall architecture of a network, such as whether
      it is arranged into one or two layers, and on the strengths of the synaptic
      connections. Specifically, for the type of single-neuron dynamics and coupling
      considered, single-layer networks are found to be very reliable, while two-layer
      networks lose their reliability with the introduction of even a small amount of
      feedback. As expected, pooled responses for large enough populations become more
      reliable, even when individual neurons are not. We also study the effects of
      noise on reliability, and find that noise that affects all neurons similarly has
      much greater impact on reliability than noise that affects each neuron
      differently. Qualitative explanations are proposed for the phenomena observed.

PMID- 19156510
TI  - Relationship between self-efficacy and physical activity among patients with type
      2 diabetes.
AB  - INTRODUCTION: While previous studies indicate a significant relationship between
      self-efficacy and physical activity, less research has focused on this
      relationship among patients with type 2 diabetes. The purpose of this
      investigation was to examine whether self-efficacy mediated the relationship
      between participation in a 1-month, print-based physical activity intervention
      and improvements in activity levels. METHODS: Participants (N = 85; mean age =
      57; 73% Caucasian; 69% female) were recruited from a community diabetes center.
      The intervention was individually-tailored based on theoretical constructs,
      including self-efficacy. RESULTS: After controlling for age, baseline activity,
      and baseline self-efficacy, the tailored intervention was associated with
      significant improvements in physical activity, 95% CI [23.01, 271.68] as well as
      self-efficacy, CI [0.02, 3.48]. There was an indirect effect of treatment on
      physical activity through self-efficacy, CI [0.77, 73.11], and the direct effect
      of treatment on physical activity was no longer significant, CI [-7.33, 253.40],
      after the influences of self-efficacy change were accounted for in the model.
      DISCUSSION: Results supported a mediation effect, such that the treatment effect
      on physical activity was completely mediated by changes in self-efficacy.
      Although replication is needed, results support the theoretical rationale for
      targeting self-efficacy to promote physical activity among patients with type 2
      diabetes.

PMID- 19156511
TI  - Assessing multiple outcomes for women with co-occurring disorders and trauma in a
      multi-site trial: a propensity score approach.
AB  - The current study assesses the ability of two promising propensity scoring
      methods to reduce selection bias in a set of secondary data from the women with
      co-occurring disorders and violence study (WCDVS), whose purpose was to evaluate
      the effect of integrated treatment for women with mental health, substance use,
      and trauma issues (N = 2,729). Weighting, the more successful method, is
      demonstrated in a re-analysis of 6- and 12-month WCDVS outcomes. In addition to
      demonstrating propensity score weighting, the current study increases confidence
      in earlier findings by considering multiple time points simultaneously and by
      controlling more completely for pre-treatment differences.

PMID- 19156513
TI  - The social production of altruism: motivations for caring action in a low-income
      urban community.
AB  - Contemporary social science paints a bleak picture of inner-city relational life.
      Indeed, the relationships of low-income, urban-residing Americans are represented
      as rife with distress, violence and family disruption. At present, no body of
      social scientific work systematically examines the factors that promote loving or
      selfless interactions among low-income, inner-city American individuals, families
      and communities. In an effort to fill that gap, this ethnographic study examined
      the motivations for altruism among a sample of adults (n = 40) who reside in an
      economically distressed housing community (i.e., housing project) in New York
      City. Content analyses of interviews indicated that participants attributed
      altruism to an interplay between 14 motives that were then ordered into four
      overarching categories of motives: (1) needs-centered motives, (2) norm-based
      motives deriving from religious/spiritual ideology, relationships and personal
      factors, (3) abstract motives (e.g., humanism), and (4) sociopolitical factors.
      The implications of these findings are discussed.

PMID- 19156512
TI  - School contextual influences on the risk for adolescent alcohol misuse.
AB  - This study investigates the association between school context and adolescent
      alcohol misuse. Data are from the first two waves of the National Longitudinal
      Study of Adolescent Health (N = 10,574 adolescents nested within 128 schools).
      Multilevel multinomial logistic regression is used to assess the association
      between school-level characteristics and the risk for non-, moderate, and heavy
      drinking. The risk for adolescent alcohol misuse varies significantly across
      schools after adjusting for adolescent-level predictors. Several school-level
      characteristics predict alcohol misuse. Notably, the risk for heavy drinking is
      elevated in schools located in communities that are socioeconomically advantaged,
      have high proportions of Non-Hispanic White residents, and are located in
      suburban (versus urban) areas. High aggregate levels of intoxication in schools
      increases the risk for heavy drinking among individual adolescents. Results
      suggest that the influence of social contexts on health is not uniform and that
      adolescent drinking is more likely in communities that are conceptualized as
      advantaged.

PMID- 19156514
TI  - Rutin supplementation in the diet has protective effects against toxicant-induced
      hippocampal injury by suppression of microglial activation and pro-inflammatory
      cytokines: protective effect of rutin against toxicant-induced hippocampal
      injury.
AB  - AIMS: Rutin is one of the flavonoids that has many beneficial effects on the
      health. Previously, we showed that rutin has a protective effect on trimethyltin
      (TMT)-induced memory dysfunction in rats. The aim of this study was to
      investigate the protective effects of rutin on TMT-induced hippocampal injury and
      the time course profiles of these effects in rats. METHODS: Four-week-old male
      Sprague-Dawley (SD) rats were fed chow with or without rutin (0.75%) during the
      experimental period and were administered with a single dose of TMT (8.5 mg/kg
      b.w., p.o.) or vehicle at 6 weeks of age. The rats were sacrificed 5, 10, or 20
      days after the TMT administration and then histological and molecular
      examinations of the hippocampus were performed. RESULTS: Rutin supplementation
      suppressed the TMT-induced decrease in the number of hippocampal pyramidal
      neurons 20 days after TMT administration. The TMT-induced up-regulation of the
      mRNA expression levels of reactive microglia marker and pro-inflammatory
      cytokines were reversed by rutin supplementation 10 or 20 days after the TMT
      administration. CONCLUSIONS: These results suggested that the neuroprotective
      effect of rutin on TMT-induced spatial memory impairment could be attributable to
      its inhibitory effect against microglial activation and its role in synapse
      formation via neurotrophic factors in the hippocampus.

PMID- 19156515
TI  - Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in
      her2/neu positive metastatic breast cancer: a multicenter phase II trial.
AB  - The combination therapy of doxorubicin and trastuzumab has been proven to be
      highly effective for metastatic breast cancer (MBC) patients with Her2/neu over
      expressing tumors. However, this regimen is characterized by frequent cardiac
      toxicity, occurring in 27% of all treated patients and aggravating when the two
      substances are given concurrently. Pegylated liposomal doxorubicin (PLD) as a
      single agent reduces significantly cardiac toxicity and maintains efficacy
      compared to conventional doxorubicin. This prospective open labeled, multicenter
      phase II study assessed the potential cardiotoxicity and efficacy of PLD and
      trastuzumab as first and second line combination therapy in Her2/neu over
      expressing MBC patients. Patients with Her2 over-expressing, measurable MBC with
      a baseline left ventricular ejection fraction (LVEF) > or =50% were treated with
      PLD 40 mg/m(2) every 4 weeks for 6 up to 9 cycles and weekly trastuzumab (4 mg/kg
      loading dose, then 2 mg/kg). Cardiotoxicity was defined as the appearance of
      clinical signs or symptoms of congestive heart failure in combination with a
      decrease in LVEF < or =44% or > or =10 units below the normal value of 50% in the
      obligatory, subsequently performed transthoracic echocardiography. Due to
      conflicting interests, the planned accrual goal of 30 patients was not reached.
      Finally 16 patients were enrolled. Ten patients presented with more than one
      metastatic site and six of them were in second-line therapy. The median LVEF in
      the study cohort was 66.1 +/- 8.68% at baseline, 62.7 +/- 5.11% after 6 cycles of
      therapy, 64.4 +/- 7.61% at the first follow up and did not change significantly
      (61.0 +/- 5.56% even at the 5th follow-up). Six out of 12 assessable patients
      (50.0%) demonstrated a clinical benefit and after a median follow-up of 15.4
      months a median progression free survival of 9.67 and a median overall survival
      of 16.23 months. Non-cardiac side effects were mild with only 3 CTC grade 3
      events of 247 treatment cycles (1.2%) and no grade 4 toxicities. The combination
      of PLD and trastuzumab in patients with Her2/neu over-expressing metastatic
      breast cancer is a safe, feasible and effective therapy. However, cardiac
      function should be monitored at close intervals. Due to the promising clinical
      response rates and mild toxicity profile in this prognostically unfavorable
      group, this combination therapy should be evaluated in larger studies.

PMID- 19156517
TI  - N-Acetylglucosamine 6-O-sulfotransferase-2 as a tumor marker for uterine cervical
      and corpus cancer.
AB  - N-Acetylglucosamine 6-O-sulfotransferase-2 (GlcNAc6ST2) is ectopically expressed
      in ovarian mucinous and clear cell adenocarcinoma [Kanoh et al., Glycoconj J
      23:453-460, 2006]. Here we studied whether GlcNAc6ST2 protein can be detected in
      sera from patients with gynecological cancers and could serve as a tumor marker.
      First, we created a monoclonal antibody and polyclonal antiserum against
      GlcNAc6ST2. These antibodies were specific for GlcNAc6ST2, as shown by Western
      blot analysis and immunoprecipitation. Using these antibodies, we constructed a
      sandwich ELISA method for detecting GlcNAc6ST2 in the serum. GlcNAc6ST2 provided
      lower positive rates for ovarian cancer than CA125, but higher positive rates for
      uterine cervical and corpus cancer than SCC antigens and CA125, respectively. A
      significantly higher percentage of stage I uterine cervical and corpus cancers
      were positive for GlcNAc6ST2 than for SCC antigens and CA125, respectively.
      GlcNAc6ST2 could therefore be a good serological marker for detecting early-stage
      uterine cervical and corpus cancers.

PMID- 19156518
TI  - Identification of high-mannose and multiantennary complex-type N-linked glycans
      containing alpha-galactose epitopes from Nurse shark IgM heavy chain.
AB  - MALDI-TOF mass spectrometry, negative ion nano-electrospray MS/MS and
      exoglycosidase digestion were used to identify 36 N-linked glycans from 19S IgM
      heavy chain derived from the nurse shark (Ginglymostoma cirratum). The major
      glycan was the high-mannose compound, Man(6)GlcNAc(2) accompanied by small
      amounts of Man(5)GlcNAc(2), Man(7)GlcNAc(2) and Man(8)GlcNAc(2). Bi- and tri
      antennary (isomer with a branched 3-antenna) complex-type glycans were also
      abundant, most contained a bisecting GlcNAc residue (beta1-->4-linked to the
      central mannose) and with varying numbers of alpha-galactose residues capping the
      antennae. Small amounts of monosialylated glycans were also found. This appears
      to be the first comprehensive study of glycosylation in this species of animal.
      The glycosylation pattern has implications for the mechanism of activation of the
      complement system by nurse shark IgM.

PMID- 19156519
TI  - Variation in colonoscopic technique and adenoma detection rates at an academic
      gastroenterology unit.
AB  - The purpose of this research is to evaluate the quality of colonoscopy at an
      academic institution with a focus on factors influencing withdrawal times and
      adenoma detection rates. Procedural data and pathologic results of 550
      consecutive screening colonoscopies in average risks patients (mean [+/-SD] age,
      57 +/- 7.6, 44% male) completed by ten academic gastroenterologists were
      reviewed. Per individual gastroenterologist, the adenoma detection rates ranged
      widely from 0.09 to 0.82 adenomas per patient with a mean of 0.46 for the group.
      The mean withdrawal time was 7.0 min for the group and ranged from 3.4 to 9.6
      min. There was a significant positive relationship between the number of adenomas
      detected and the withdrawal time (P = 0.006). Endoscopists with cecal intubation
      time to withdrawal time ratios of less than 1 detected significantly more
      adenomas compared to endoscopists with ratios greater than 1 (P = 0.001). (1)
      Significant variation in academic gastroenterologists' abilities to detect
      adenomas during screening colonoscopies exists. (2) Colonoscopic withdrawal time
      and the cecal intubation to withdrawal time ratio are important factors
      associated with increased adenoma detection rates.

PMID- 19156520
TI  - Alcohol drinking may not be a major risk factor for fatty liver in Japanese
      undergoing a health checkup.
AB  - The question of whether alcohol drinking is a risk factor for fatty liver as
      shown by ultrasonography was investigated by both cross-sectional and
      longitudinal approaches in Japanese undergoing a health checkup. In this cross
      sectional study, 32,438 males (49.0 +/- 11.9 years old) and 31,009 females (48.2
      +/- 11.6 years old) receiving a health checkup from 2000 to 2005 were included.
      Longitudinally, 5,444 males (49.8 +/- 10.7 years old) and 4,980 females (50.4 +/-
      9.3 years old) participating in both 2000 and 2005 were included. Multiple
      logistic regression analyses were performed for both sexes, adjusted for age,
      BMI, and smoking. The prevalence of fatty liver in non-, occasional, daily
      moderate, and daily heavy drinkers was 28.5, 27.5, 18.7, and 19.1% in men and
      12.4, 7.7, 5.4, and 6.7% in women, respectively (inverse association, P < or =
      0.05 for both). Occasional, daily moderate, and daily heavy drinking in men and
      occasional and daily moderate drinking in women were inversely associated with
      fatty liver in the cross-sectional study. Daily moderate and heavy drinking
      appeared protective in men in the longitudinal study. Alcohol drinking may not be
      a major risk for fatty liver in Japanese undergoing a health checkup.

PMID- 19156521
TI  - The strategy of combined ischemia preconditioning and salvianolic acid-B
      pretreatment to prevent hepatic ischemia-reperfusion injury in rats.
AB  - BACKGROUND: Ischemia-reperfusion injury (IRI) is a serious complication of liver
      surgery, especially for extended hepatectomy and liver transplantation. The aim
      of this study was to evaluate the protective effect of combined ischemic
      preconditioning (IPC) and salvianolic acid-B (Sal-B) pretreatment against IRI
      induced hepatocellular injury. METHODS: Sixty male Wistar rats weighing around
      200 g were randomized into five groups (n=12): sham group: only anesthesia and
      laparotomy; IR group: 90 min sustained ischemia by blocking the left ortal
      vessels; IPC group: 10 min ischemia and 10 min reperfusion prior to the sustained
      ischemia; Sal-B group: 10 mg/kg injection of Sal-B intravenously 10 min prior to
      the sustained ischemia; IPC+Sal-B group: same IPC procedure as in IPC group, but
      proceeded by intravenous administration of Sal-B 10 min prior to sustained
      ischemia. After 5 h of reperfusion, serum levels of ALT and AST were measured;
      the amount of malondialdehyde (MDA) and adenine nucleotides in liver tissue was
      determined; the expression of Bcl-2 and caspase-3 was detected by
      immunofluorescent and western blotting techniques; the severity of apoptosis and
      pathological alterations was evaluated by TUNEL and H&E staining, respectively.
      RESULTS: The serum aminotransferases, hepatic MDA concentration, and apoptotic
      index in groups IPC, Sal-B, and IPC+Sal-B were significantly lower than those in
      the IR group (P<0.001), while the IPC+Sal-B group had the lowest values among
      these groups (P<0.05). Compared with the IR group, groups IPC and Sal-B not only
      had statistically higher ATP levels and energy charge (EC) values (P<0.01), but
      also had upregulated Bcl-2 expression and downregulated cleaved caspase-3
      expression in liver tissue. All these effects were further augmented in the
      IPC+Sal-B group. Liver histopathological findings were consistent with these
      results. CONCLUSIONS: Based on these results, the combined IPC and Sal-B
      pretreatment had a synergistically protective effect on liver tissue against IRI,
      which might be due to decreased post-ischemic oxidative stress, improved energy
      metabolism, and reduced hepatocellular apoptosis.

PMID- 19156522
TI  - Liver transplantation for hepatocellular carcinoma in the MELD era: leading roles
      of MELD score, AFP level, and recipient age as predictors of survival.

PMID- 19156523
TI  - Prevalence of overweight and obesity in Chinese American children in New York
      City.
AB  - Childhood obesity has been a growing concern in recent years. The extent of
      obesity in various ethnic pediatric populations including Chinese Americans has
      not been fully explored. In this study, the prevalence of overweight and obesity
      in a Chinese American pediatric population (6-19 years) was determined through a
      chart review of 4,695 patients from a large community health center in New York
      City. Demographic characteristics including sex, age and immigrant status were
      used in a logistic regression to determine risk factors for obesity in this
      community. Overall, 24.6% of the children studied were overweight or obese
      (defined as BMI > or = 85th percentile for age and sex). Among US born boys aged
      6-12 years, the combined prevalence of overweight and obesity was found to be as
      high as 40%. Further studies are needed to understand the complex interplay of
      factors that contribute to obesity in pediatric immigrant groups.

PMID- 19156524
TI  - La Clinica del Pueblo: a model of collaboration between a private media
      broadcasting corporation and an academic medical center for health education for
      North Carolina Latinos.
AB  - La Clinica del Pueblo, a health education collaboration between the Maya Angelou
      Center for Health Equity at Wake Forest University School of Medicine and Que
      Pasa Media, Inc., disseminates culturally appropriate health information to the
      North Carolina (NC) Latino community. The program includes a weekly radio show
      and corresponding newspaper column addressing four areas: childhood health, adult
      health, safety, and utilization. The radio show format includes a didactic
      presentation followed by a call-in question and answer period. Over 200
      consecutive weeks of programming have been completed, averaging 11 calls per
      show. A Latino healthcare resource guide and hotline also provide resource
      information. Participant demographic information indicates that 50% of the target
      population comes from Mexico, 60% are women, and 70% of the community is younger
      than 38 years. There was an increase in the use of the media as a source of
      health information over the course of the project, from an initial 33% of
      respondents to 58% in the last survey. Listenership to La Clinica del Pueblo
      displayed a pronounced increase (18% initial survey to 55% in last survey, P <
      0.05). We also observed a statistically significant increase in medical knowledge
      from initial survey to the last survey (P < 0.001). By multiple regression
      analysis, we identified 4 predictors of medical knowledge: order of surveys (1 <
      3, P < 0.001), education level (P < 0.0001), female gender (P < 0.01) and radio
      listenership (P < 0.05). The first three variables predicted higher scores;
      however, radio listening recognition of our radio program was more common among
      individuals who had lower scores. In conclusion, La Clinica del Pueblo is a model
      for a novel approach that can reach the Latino community to improve medical
      knowledge and possibly affect health behaviors in a positive manner.

PMID- 19156525
TI  - Development and validation of a computational musculoskeletal model of the elbow
      and forearm.
AB  - Computational modeling is a powerful tool to study normal, injured, and repaired
      joint function. Existing musculoskeletal models of the elbow have all limited
      their applicability by assuming fixed joint axes of rotation or prescribing
      specific kinematics. The purpose of this study was to develop and validate a
      model of the elbow and forearm whereby joint behavior was dictated by articular
      contact, ligamentous constraints, muscle loading, and external perturbations. A
      three-dimensional computer representation of the humerus, ulna, and radius was
      produced from computed tomography scans, ligaments were modeled as linear
      springs, select muscles were represented as constant-magnitude force vectors, and
      reaction forces were automatically applied at points of bone-to-bone contact. A
      commercial rigid body dynamics program was used to simulate joint function, and
      validation was accomplished through a comparison of model predictions to results
      obtained in published studies which explored elbow range of motion and the
      effects of coronoid process removal on joint stability. The computational model
      accurately predicted flexion-extension motion limits, and relationships between
      coronoid process removal, flexion angle, and varus constraining forces. The model
      was also able to compute parameters that the experimental investigations could
      not, such as forces within ligaments and contact forces between bones. The
      potential medical applications for this model and modeling approach are
      significant, and are anticipated to ultimately have value as a predictive
      clinical tool.

PMID- 19156526
TI  - Proliferating cell nuclear antigen destabilizes c-Abl tyrosine kinase and
      regulates cell apoptosis in response to DNA damage.
AB  - The tyrosine kinase, c-Abl, plays important roles in many aspects of cellular
      function. The activity of c-Abl is tightly controlled, but the underlying
      mechanism is unclear. Recent studies suggest that c-Abl function is regulated by
      distinct lipids in different cell types. In the present study, we show that the
      DNA replication factor, proliferating cell nuclear antigen (PCNA), interacts with
      c-Abl and destabilizes c-Abl by promoting its polyubiquitination and degradation.
      Moreover, deletion of a domain in c-Abl, the PIP box, disrupts its interaction
      with PCNA, abolishes the PCNA-induced degradation of nuclear c-Abl, and
      substantially increases the nuclear c-Abl apoptotic function. These findings
      indicate that PCNA negatively regulates the stability of c-Abl and thereby
      inhibits apoptosis in the response to DNA damage.

PMID- 19156527
TI  - Inflammasomes in infection and inflammation.
AB  - Two of the main challenges that multicellular organisms faced during evolution
      were to cope with invading microorganisms and eliminate and replace dying cells.
      Our innate immune system evolved to handle both tasks. Key aspects of innate
      immunity are the detection of invaders or tissue injury and the activation of
      inflammation that alarms the system through the action of cytokine and chemokine
      cascades. While inflammation is essential for host resistance to infections, it
      is detrimental when produced chronically or in excess and is linked to various
      diseases, most notably auto-immune diseases, auto-inflammatory disorders, cancer
      and septic shock. Essential regulators of inflammation are enzymes termed "the
      inflammatory caspases". They are activated by cellular sensors of danger signals,
      the inflammasomes, and subsequently convert pro-inflammatory cytokines into their
      mature active forms. In addition, they regulate non-conventional protein
      secretion of alarmins and cytokines, glycolysis and lipid biogenesis, and the
      execution of an inflammatory form of cell death termed "pyroptosis". By acting as
      key regulators of inflammation, energy metabolism and cell death, inflammatory
      caspases and inflammasomes exert profound influences on innate immunity and
      infectious and non-infectious inflammatory diseases.

PMID- 19156529
TI  - Interactions between cycloguanil derivatives and wild type and resistance
      associated mutant Plasmodium falciparum dihydrofolate reductases.
AB  - Comparative molecular field analysis (CoMFA) and quantum chemical calculations
      were performed on cycloguanil (Cyc) derivatives of the wild type and the
      quadruple mutant (Asn51Ile, Cys59Arg, Ser108Asn, Ile164Leu) of Plasmodium
      falciparum dihydrofolate reductase (PfDHFR). The represented CoMFA models of wild
      type (r(2) = 0.727 and r(2) = 0.985) and mutant type (r(2) = 0.786 and r(2) =
      0.979) can describe the differences of the Cyc structural requirements for the
      two types of PfDHFR enzymes and can be useful to guide the design of new
      inhibitors. Moreover, the obtained particular interaction energies between the
      Cyc and the surrounding residues in the binding pocket indicated that Asn108 of
      mutant enzyme was the cause of Cyc resistance by producing steric clash with p-Cl
      of Cyc. Consequently, comparing the energy contributions with the potent flexible
      WR99210 inhibitor, it was found that the key mutant residue, Asn108, demonstrates
      attractive interaction with this inhibitor and some residues, Leu46, Ile112,
      Pro113, Phe116, and Leu119, seem to perform as second binding site with WR99210.
      Therefore, quantum chemical calculations can be useful for investigating residue
      interactions to clarify the cause of drug resistance.

PMID- 19156528
TI  - Bcl2 family proteins in carcinogenesis and the treatment of cancer.
AB  - Deregulation of Bcl2 family members is a frequent feature of human malignant
      diseases and causal for therapy resistance. A number of studies have recently
      shed light onto the role of pro- and anti-apoptotic Bcl2 family members in tumour
      pathogenesis and in mediating the effects of classical as well as novel front
      line anticancer agents, allowing the development of more efficient and more
      precisely targeted treatment regimens. Most excitingly, recent progress in our
      understanding of how Bcl2-like proteins maintain or perturb mitochondrial
      integrity has finally enabled the development of rational-design based anticancer
      therapies that directly target Bcl2 regulated events at the level of
      mitochondria. This review aims to give an overview on the most recent findings on
      the role of the Bcl2 family in tumour development in model systems of cancer, to
      relate these findings with observations made in human pathologies and drug
      action.

PMID- 19156530
TI  - Sumoylation precedes accumulation of phosphorylated H2AX on sex chromosomes
      during their meiotic inactivation.
AB  - During meiosis in male mammals, X and Y chromosomes undergo the process of
      meiotic sex chromosome inactivation (MSCI). A crucial role in MSCI has recently
      been reported for BRCA1, ATR kinase, and phosphorylated histone H2AX, but the
      exact mechanism remains to be determined. Small ubiquitin-like modifier (SUMO)
      proteins have recently been shown to localize to the sex body in mouse meiotic
      spermatocytes, but the role they play during MSCI is unknown. In this study, in
      order to better understand the molecular events of MSCI, we followed dynamic
      changes in gammaH2AX and SUMO localization patterns during MSCI. Using confocal
      laser scanning microscopy (CLSM) as an analytical tool for visualizing numerous
      spermatocytes from the same development stage and for consecutively following the
      meiotic progression, we were able to demonstrate a very early appearance of SUMO
      1, which preceded gammaH2AX accumulation on the sex chromosomes during their
      meiotic inactivation. In contrast to SUMO-1, SUMO-2/3 was undetectable in
      zygotene spermatocytes, suggesting a possible specific role for SUMO-1 in the
      initiation of MSCI.

PMID- 19156531
TI  - Relationships between cancer and aging: a multilevel approach.
AB  - The incidence of cancer increases with age in humans and in laboratory animals
      alike. There are different patterns of age-related distribution of tumors in
      different organs and tissues. Aging may increase or decrease the susceptibility
      of various tissues to initiation of carcinogenesis and usually facilitates
      promotion and progression of carcinogenesis. Aging may predispose to cancer in
      two ways: tissue accumulation of cells in late stages of carcinogenesis and
      alterations in internal homeostasis, in particular, alterations in immune and
      endocrine systems. Increased susceptibility to the effects of tumor promoters is
      found both in aged animals and aged humans, as predicted by the multistage model
      of carcinogenesis. Aging is associated with a number of events at the molecular,
      cellular and physiological levels that influence carcinogenesis and subsequent
      cancer growth. An improved understanding of age-associated variables impacting on
      the tumor microenvironment, as well as the cancer cells themselves, will result
      in improved treatment modalities in geriatric oncology.

PMID- 19156532
TI  - Metabolic constraints on the eukaryotic transition.
AB  - Mutualism, obligate mutualism, symbiosis, and the eukaryotic 'fusion' of Serial
      Endosymbiosis Theory represent progressively more rapid and less distorted real
      time communication between biological structures instantiating information
      sources. Such progression in accurate information transmission requires, in turn,
      progressively greater channel capacity that, through the homology between
      information source uncertainty and free energy density, requires ever more
      energetic metabolism. The eukaryotic transition, according to this model, may
      have been entrained by an ecosystem resilience shift from anaerobic to aerobic
      metabolism.

PMID- 19156534
TI  - Immune deficits in allogeneic hematopoietic stem cell transplant (HSCT)
      recipients.
AB  - Immune deficits account for the high frequency of life threatening bacterial,
      viral, and fungal opportunistic infections seen in allogeneic HSCT recipients.
      Despite advances in infectious disease management, the integrity of host defenses
      remains the mainstay of defense. The intensity of the preparative regimen, degree
      of HLA matching, source of stem cells (marrow, blood, or cord), extent of T-cell
      depletion, and immunosuppressive therapy are some of the factors that impact the
      kinetics, characteristics, and quality of immune reconstitution. Graft-versus
      host disease and its prophylaxis or treatment produce a host environment that is
      particularly vulnerable to infections. Mucosal disruption and prolonged severe
      neutropenia usually confine their impact to the early course of transplant. After
      initial engraftment, HSCT recipients remain at great risk for opportunistic
      infections and this is related to prolonged and severe T-lymphocyte dysfunction
      of a complex multifactorial nature. B cell dysfunction is less problematic
      clinically, but includes deficiencies of immunoglobulin subclasses and impaired
      ability to mount a vaccine response. Advances in understanding of these immune
      deficits have resulted in successful strategies including revaccination, growth
      factors, thymic protection, and adoptive cellular therapy with antigen-specific
      cells.

PMID- 19156535
TI  - Eupenicillium saturniforme, a new species discovered from Northeast China.
AB  - A new Eupenicillium species, E. saturniforme was isolated from soil in Jilin
      Province, northeast China. Morphologically, it resembled E. shearii and E.
      tropicum, but is distinguished from them by slowly maturing cleistothecia,
      lenticular ascospores with nearly smooth-walled convex surfaces, strictly
      velutinous colony texture with abundant conidiogenesis, robust biverticillate
      penicilli, apically vesiculate metulae and rough-walled stipes and conidia. The
      partial beta-tubulin gene sequence of the new species (EU644080) showed
      relationship with Penicillium glabrum in the BLAST search in GenBank. Further
      analyses of partial calmodulin and ribosomal DNA internally transcribed spacer 1
      5.8S-internally transcribed spacer 2 (rDNA ITS1-5.8S-ITS2) sequence data
      confirmed that E. saturniforme fell in the clade with P. glabrum, P. lividum, P.
      purpurascens, P. spinulosum and P. thomii of Subgenus Aspergilloides. However, E.
      saturniforme is a distinctive species lacking close relatives among described
      species of penicillia.

PMID- 19156536
TI  - In vitro modulation of TCF7L2 gene expression in human pancreatic cells.
AB  - Several studies have recently reported strong association between type 2 diabetes
      and variation in the transcription factor 7-like 2 (TCF7L2) gene, which has been
      confirmed by several other genome-wide studies. However, the physiological
      implications of this transcription factor on the pathogenesis of type 2 diabetes
      is not yet known. The aim of this study was to investigate the alteration in
      TCF7L2 gene expression in human pancreatic cell line in response to various
      factors in vitro. MIA Paca-2 cell line (Human Pancreas cell line) was cultured in
      the presence of curcumin, lipopolysaccaride and glucose (low and high
      concentration). TCF7L2 gene expression was determined using quantitative real
      time RT-PCR. Treatment with curcumin significantly increased TCF7L2 gene
      expression to 3.24 fold (1.7-log fold) (P = 0.003) compared to the controls while
      treatment with LPS decreased TCF7L2 gene expression to 0.88-fold (-0.18-log). On
      the other hand, glucose increased TCF7L2 gene expression in pancreatic cell line.
      Our data suggest a role for TCF7L2 in glucose homeostasis. The contrary effect of
      curcumin and LPS on expression of TCF7L2 in pancreatic cells supports a role for
      TCF7L2 in their survival and function in inflammatory conditions.

PMID- 19156537
TI  - Implementing the Netherlands code of conduct for scientific practice-a case
      study.
AB  - Widespread enthusiasm for establishing scientific codes of conduct
      notwithstanding, the utility of such codes in influencing scientific practice is
      not self-evident. It largely depends on the implementation phase following their
      establishment--a phase which often receives little attention. The aim of this
      paper is to provide recommendations for guiding effective implementation through
      an assessment of one particular code of conduct in one particular institute.
      Based on a series of interviews held with researchers at the Department of
      Biotechnology of Delft University of Technology, this paper evaluates how the
      Netherlands Code of Conduct for Scientific Practice is received by those it is
      supposed to govern. While respondents agreed that discussion of the guiding
      principles of scientific conduct is called for, they did not consider the code as
      such to be a useful instrument. As a tool for the individual scientific
      practitioner, the code leaves a number of important questions unanswered in
      relation to visibility, enforcement, integration with daily practice and the
      distribution of responsibility. Recommendations are provided on the basis of
      these questions. There is more at stake than merely holding scientific
      practitioners to a proper exercise of their duties; implementation of scientific
      society codes of conduct also concerns the further motives and value commitments
      that gave rise to their establishment in the first place.

PMID- 19156538
TI  - Polish Research Ethics Committees in the European Union system of assessing
      medical experiments.
AB  - The Polish equivalents of Research Ethics Committees are Bioethics Committees
      (BCs). A questionnaire study has been undertaken to determine their situation.
      The BC is usually comprised of 13 members. Nine of these are doctors and four are
      non-doctors. In 2006 BCs assessed an average of 27.3 +/- 31.7 (range: 0-131)
      projects of clinical trials and 71.1 +/- 139.8 (range: 0-638) projects of other
      types of medical research. During one BC meeting an average of 10.3 +/- 14.7
      (range: 0-71) projects of medical research were assessed (2006). The amendment of
      Polish laws according with Directive 2001/20/EC caused a percentage increase in
      BCs which assessed less than 20 projects per year (16% vs. 33% or 42% in 2003 vs.
      2005 or 2006 respectively, p < 0,05). The results confirm the usefulness of the
      current practice of creating BCs by medical universities, medical institutes and
      regional chambers of physicians and dentists but rationalization of the workload
      for individual BCs is necessary.

PMID- 19156540
TI  - Report on the fifth international workshop on the CCN family of genes.
AB  - The Fifth International Workshop on the CCN Family of Genes was held in Toronto
      October 18-22, 2008. This bi-annual workshop provides a unique opportunity for
      the presentation and discussion of cutting edge research in the CCN field. The
      CCN family members have emerged as extracellular matrix associated proteins which
      play a crucial role in cardiovascular and skeletal development, fibrosis and
      cancer. Significant progress has been made in the development of model systems to
      tease apart the CCN signalling pathways in these systems. Results presented at
      the conference suggest that targeting these pathways now shows real promise as a
      therapeutic strategy.

PMID- 19156539
TI  - Connective tissue growth factor (CTGF, CCN2) gene regulation: a potent clinical
      bio-marker of fibroproliferative disease?
AB  - The CCN (cyr61, ctgf, nov) family of modular proteins regulate diverse biological
      affects including cell adhesion, matrix production, tissue remodelling,
      proliferation and differentiation. Recent targeted gene disruption studies have
      demonstrated the CCN family to be developmentally essential for chondrogenesis,
      osteogenesis and angiogenesis. CCN2 is induced by agents such as angiotensin II,
      endothelin-1, glucocorticoids, HGF, TGFbeta, and VEGF, and by hypoxia and
      biomechanical and shear stress. Dysregulated expression of CCN2 has also been
      widely documented in many fibroproliferative diseases. This mini-review will
      focus on CCN2, and the recent progress in understanding CCN2 gene regulation in
      health and disease. That CCN2 should be considered a novel and informative
      surrogate clinical bio-marker for fibroproliferative disease is discussed.

PMID- 19156542
TI  - The role of postoperative radiation therapy (PORT) in the treatment of
      extrahepatic bile duct cancer: a surveillance, epidemiology, and end results
      (SEER) population-based investigation.
AB  - PURPOSE: Extrahepatic bile duct cancers (EBDC) are aggressive cancers for which
      the importance of the use of postoperative radiation therapy (PORT) in
      potentially curative cases remains the subject of clinical investigation.
      METHODS: The 1973-2004 National Cancer Institute Surveillance Epidemiology and
      End Results (SEER) database was analyzed for patients with EBDC who had undergone
      cancer-directed surgery. Patients who died <3 months after surgery were excluded
      from analysis. Patients with distant metastases, with unknown stage or
      interventions, or benign histologies were excluded. RESULTS: Nine hundred fifty
      six patients were selected. Tumor-related factors, such as regional (vs. local)
      disease and an increasing number of lymph nodes predicted for the delivery of
      PORT. In unadjusted univariate analysis, patients treated from 1973 to 2004 who
      fit the selection criteria had a lower 3-year survival rate if they received PORT
      vs. no PORT (3 year survival 31.3% vs. 39.6%, p = 0.04), but this improvement did
      not hold in multivariate survival analysis or in univariate analysis of patient
      subsets. CONCLUSIONS: Based on analysis of the SEER database, there was no
      definitive evidence for improved survival with the addition of PORT to radical
      surgery. This analysis should be approached with caution given its observational
      and retrospective nature. In addition, it should be remembered that the SEER
      database lacks information on the use of chemotherapy, radiation technique, and
      the completeness of resection.

PMID- 19156541
TI  - The Cdk5/p35 kinases modulate leptin-induced STAT3 signaling.
AB  - Cyclin-dependent kinase (Cdk) 5 is ubiquitously expressed in the brain and plays
      an essential role in central nervous system development and synaptic plasticity.
      The p35 kinase is a neuronal specific activator of Cdk5. Here, we show for the
      first time that Cdk5 activation modulates leptin signaling. P35 and its
      metabolite p25 were colocalized with the leptin receptor ObR in selective neurons
      in the hypothalamus. Overexpression of p35 alone was sufficient to induce the
      transcriptional activation of signal transducer and activator of transcription 3
      (STAT3) in a cellular model. In retinoic acid-differentiated SH-SY5Y neuronal
      cells where ObRb was induced, leptin increased the expression of Cdk5, p35, and
      p25 kinases. The time course of induction coincided with that of phosphorylated
      (p)-STAT3. When Cdk5 activity was inhibited, either by roscovitine or
      overexpression of dominant negative Cdk5, there was a reduction of pSTAT3
      activation. The results show that the activation of Cdk5 by p35 sustained leptin
      induced pSTAT3 at 3-6 h. Thus, p35 is a novel modulator of leptin-induced STAT3
      signaling.

PMID- 19156543
TI  - Fully automated processing of fMRI data in SPM: from MRI scanner to PACS.
AB  - Here we describe the Wake Forest University Pipeline, a fully automated method
      for the processing of fMRI data using SPM. The method includes fully automated
      data transfer and archiving from the point of acquisition, real-time batch script
      generation, distributed grid processing, interface to SPM in MATLAB, error
      recovery and data provenance, DICOM conversion and PACS insertion. It has been
      used for automated processing of fMRI experiments, as well as for the clinical
      implementation of fMRI and spin-tag perfusion imaging. The pipeline requires no
      manual intervention, and can be extended to any studies requiring offline
      processing.

PMID- 19156544
TI  - Activity-dependent dendritic release of BDNF and biological consequences.
AB  - Network construction and reorganization is modulated by the level and pattern of
      synaptic activity generated in the nervous system. During the past decades,
      neurotrophins, and in particular brain-derived neurotrophic factor (BDNF), have
      emerged as attractive candidates for linking synaptic activity and brain
      plasticity. Thus, neurotrophin expression and secretion are under the control of
      activity-dependent mechanisms and, besides their classical role in supporting
      neuronal survival neurotrophins, modulate nearly all key steps of network
      construction from neuronal migration to experience-dependent refinement of local
      connections. In this paper, we provide an overview of recent findings showing
      that BDNF can serve as a target-derived messenger for activity-dependent synaptic
      plasticity and development at the single cell level.

PMID- 19156545
TI  - Human scavenger receptor class B type 1 is regulated by activators of peroxisome
      proliferators-activated receptor-gamma in hepatocytes.
AB  - High-density lipoprotein (HDL) particles play a critical role in cholesterol
      metabolism. The hepatic scavenger receptor class B type I (SR-B1) binds HDL
      particles for mediating reverse cholesterol transport (RCT), thus lowering the
      risk of atherosclerosis. Thiazolidinediones (TZDs), known to have potent
      enhancing effects on insulin sensitivity, have been developed for the treatment
      of non-insulin-dependent diabetes mellitus. They are a high-affinity ligand for
      the peroxisome proliferator-activated receptor gamma (PPAR-gamma), which belongs
      to a nuclear receptor superfamily. In this study, we examined the effects of
      thiazolidinedione PPAR-gamma on hepatic SR-B1 gene expression in human hepatoma
      G2 cell-line (HepG2). Results showed that hepatic SR-B1 mRNA and protein were
      increased on exposure to thiazolidinediones. Transcriptional activity of human SR
      B1 (hSR-B1) gene paralleled the endogenous expression of the gene and was
      dependent on the dose of thiazolidinediones. We investigated the influence on the
      promoter activity of vector expressing PPAR and retinoid X receptor (RXR),
      cotransfected into the HepG2 cells along with SR-B1 promoter-reporter gene
      constructs. PPAR-gamma and RXR sufficiently induced the SR-B1 promoter activity
      in the HepG2 cells. Chromatin immunoprecipitation (ChIP) assay confirmed the
      binding of the PPAR-gamma to the SR-B1 promoter region. The mutagenesis of this
      binding site abolished the ability of the thiazolidinediones or PPARs to
      stimulate promoter activity. Together, these results indicate that the
      stimulation of SR-B1 expression in the liver is mediated in part by activation of
      the PPAR-gamma and RXR, and raise the possibility that this stimulation using
      thiazolidinediones conditions provides a protective mechanism for accelerated
      atherosclerosis in diabetes mellitus.

PMID- 19156546
TI  - Relationship between basal metabolic rate and cortisol secretion throughout
      pregnancy.
AB  - The role of cortisol in mediating basal metabolic rate (BMR) changes that
      accompany the adjustment of maternal body weight (BW) and body composition during
      pregnancy is unknown. We tested whether increase in BMR during pregnancy is
      explained by variations in cortisol secretion. Longitudinal changes in BW, fat
      mass (FM), fat-free mass (FFM), BMR, hormonal, and metabolic parameters in 31
      parous Caucasian women at gestational weeks 12, 26, and 36 were examined.
      Individual differences (Delta) between the last and the first measurement
      occasions for each variable were calculated. By gestational week 36, BW and BMR
      increased while both FFM/FM and BMR/BW ratio decreased (P < 0.001 for all)
      suggesting higher proportion of FM accretion. Cortisol, leptin, and insulin-like
      growth factor-1 (IGF-1) concentration rose, whereas non-placental growth hormone
      (GH) and thyroid hormones declined (P < 0.001 for all). Insulin resistance
      changed; basal glucose (P < 0.001) and ghrelin (P < 0.014) declined, whereas
      insulin (P < 0.001), homeostatic model index (HOMA-IR) (P = 0.041), and free
      fatty acid (FFA) concentration (P = 0.007) increased. The elevation in BMR showed
      inverse correlations with DeltaBW (r = 0.37, P = 0.047) and Deltacortisol (r = 
      0.53, P = 0.004). Significant portion (51.6%) of the variation in BMR change was
      explained by increases of cortisol (27.1%), FFA (13.4%), and free
      triiodothyronine (11.1%). In conclusion, the changes in maternal cortisol
      concentration are in relationship with changes in BMR and BW, further suggesting
      that increased cortisol secretion during pregnancy could be linked with the
      maintenance of maternal BW and body composition.

PMID- 19156547
TI  - Developmental regulation of the expression of the transferrin receptor and Ki67
      in oocytes of the baboon fetal ovary by estrogen.
AB  - We previously showed that estrogen regulates baboon fetal ovarian follicle
      development and oocyte integrity. Because iron incorporated into cells by the
      transferrin receptor is essential for cell/nuclear function, we determined
      whether fetal oocyte expression of transferrin receptor and the nuclear protein
      Ki67 were developmentally regulated by estrogen and associated with DNA
      integrity/fragmentation. Transferrin-receptor expression was minimal at
      midgestation and abundant in late gestation and localized to the cytoplasm and
      surface of oocytes of primordial follicles. Expression of transferrin receptor,
      however, was negligible in oocytes in fetuses in which serum estradiol-17beta
      levels were suppressed (>95%) by daily maternal treatment between mid- and late
      gestation with the aromatase inhibitor letrozole and partially restored by
      treatment with letrozole and estradiol benzoate. Ki67 was localized to
      pregranulosa and germ cells at midgestation and throughout the oocyte nucleus in
      late gestation in estrogen-replete fetuses. In contrast, in estrogen-suppressed
      fetuses, Ki67 was localized to a limited number of foci around the oocyte
      nucleus. Apoptosis detected in pregranulosa and germ cells at midgestation was
      not observed in late gestation in estrogen-replete/-suppressed fetuses. We
      conclude that estrogen regulates fetal oocyte transferrin-receptor expression and
      that inhibition of receptor development is associated with alterations in Ki67
      expression by the oocyte but not apoptosis. Collectively, these results and our
      previous studies further define the essential role of estrogen in regulating
      development of follicles comprised of healthy oocytes by the baboon fetal ovary.

PMID- 19156548
TI  - Molecular detection of Streptococcus pyogenes and Streptococcus dysgalactiae
      subsp. equisimilis.
AB  - We developed molecular diagnostic assays for the detection of Streptococcus
      pyogenes (GAS) and Streptococcus dysgalactiae subsp. equisimilis (SDSE), two
      streptococcal pathogens known to cause both pharyngitis and more invasive forms
      of disease in humans. Two real-time PCR assays coupled with an internal control
      were designed to be performed in parallel. One assay utilizes a gene target
      specific to GAS, and the other utilizes a gene target common to the two species.
      Both assays showed 2-3 orders of magnitude improved analytical sensitivity when
      compared to a commercially available rapid antigen test. In addition, when
      compared to standard culture in an analysis of 96 throat swabs, the real-time PCR
      assays resulted in clinical sensitivity and specificity of 91.7 and 100%,
      respectively. As capital equipment costs for real-time PCR can be prohibitive in
      smaller laboratories, the real-time PCR assays were converted to a low-density
      microarray format designed to function with an inexpensive photopolymerization
      based non-enzymatic signal amplification (NESA) method. S. pyogenes was
      successfully detected on the low-density microarray in less than 4 h from sample
      extraction through detection.

PMID- 19156549
TI  - Phenoxodiol treatment alters the subsequent response of ENOX2 (tNOX) and growth
      of hela cells to paclitaxel and cisplatin.
AB  - Phenoxodiol is an experimental anticancer drug under development as a
      chemosensitizer intended to reverse multidrug resistance mechanisms in ovarian
      and prostate cancer cells to most standard cytotoxics. The putative molecular
      target of phenoxodiol is a cell-surface, tumor-specific NADH oxidase, ENOX2
      (tNOX), with phenoxodiol having no apparent effect on the constitutive form of
      this enzyme ENOX1 (CNOX). Using ENOX2 as the target, this study was conducted to
      explore the temporal relationship between phenoxodiol and paclitaxel or cisplatin
      in achieving chemosensitization in HeLa cells which are relatively resistant to
      both paclitaxel and cisplatin. Sequential addition of phenoxodiol and paclitaxel
      or phenoxodiol and cisplatin showed greater inhibition of HeLa cell ENOX1
      activity and growth compared to adding the drugs simultaneously or individually.
      In parallel, a similar chemosensitizing response of phenoxodiol for cisplatin was
      observed. ENOX1 was not affected and trans-platinum had no effect. With spent
      media from phenoxodiol-treated cells sensitivity was enhanced to both paclitaxel
      and cisplatin if the cells were first pretreated with phenoxodiol. Similar
      results were obtained with ENOX2-enriched preparations stripped from the surfaces
      of phenoxodiol-treated cells. In keeping with a speculative prion model, it seems
      as though the ENOX2 "remembers" the phenoxodiol and "teaches" other ENOX2
      molecules to respond to paclitaxel and cisplatin as if phenoxodiol were still
      present.

PMID- 19156550
TI  - Triple-negative breast cancer: immunohistochemical correlation with basaloid
      markers and prognostic value of survivin.
AB  - OBJECTIVE: Among the subgroups of breast cancer, basaloid type has the shortest
      disease-free survival. Survivin is an apoptosis inhibitor and its prognostic and
      predictive value in breast cancer is under investigation. In this study, we
      examined the basaloid markers CK5/6, CK14, CK17, and EGFR in triplet-negative
      patients and evaluated the impact of survivin on survival. MATERIALS AND METHODS:
      Thirty patients with breast cancer in triplet-negative form admitted to Erciyes
      University Medical Oncology Department between 2001 and 2005 were included in the
      study. Median follow up and age were 45 months (range 5-76 months) and 47 years
      (range 23-76), respectively. Eighteen patients (60%) were premenopausal and 12
      (40%) were postmenopausal. In total, 2, 12, and 14 patients had stage I, II, and
      III disease, respectively. When cytokeratines and survivin were analyzed
      independently, association between CK5/6 positivity and lymph node involvement
      was statistically significant (P = 0.014). In 70% of patients, CK5/6 or EGFR was
      found positive, and positive results were only had statistically significant
      correlation with age and menopausal status (P = 0.049 and 0.049, respectively).
      Ten patients (33.3%) totally and nine patients (42.8%) in the basaloid subgroup
      had positive staining for survivin. Survivin was not correlated with any of the
      clinical or histopathological features. While correlation between the number of
      involved lymph nodes, lymphovascular invasion, histopathological grade, and
      disease-free survival was statistically significant (P = 0.036, 0.002, and 0.035,
      respectively), this is not valid for CK5/6, EGFR, and survivin. CONCLUSION: CK5/6
      or EGFR was accepted as determinants of basaloid breast cancer. The correlation
      between basaloid form and other histopathological markers did not reveal any
      significant difference with respect to prognostic and clinical parameters. We
      were unable to demonstrate the prognostic impact of survivin in patients with
      basaloid form or triplet-negative breast cancer.

PMID- 19156551
TI  - Long-term effect of Spirulina platensis extract on DMBA-induced hamster buccal
      pouch carcinogenesis (immunohistochemical study).
AB  - In cancer research, the use of complementary and alternative medicine has
      increased over the past decade. In this study, 80 male golden Syrian hamsters
      were divided into four equal groups; the right buccal pouches of the hamster rats
      in group 1 were painted with 0.5% solution of 7, 12-dimethylbenz[a]anthracene
      (DMBA), three times a week for 32 weeks. The same pouches of group 2 were
      subjected to the same DMBA painting; but at the same time, the animals received
      10 mg/daily Spirulina platensis extract for the same period. In group 3, the same
      regimen of DMBA painting was done but for 24 weeks only and the daily
      systemically S. platensis was received for the 32 weeks. In group 4, neither DMBA
      painting nor S. platensis administration was done but pouches were painted with
      saline and served as a control one. Five rats from each group were sacrificed at
      12, 24, 28, and 32 weeks, respectively. The required pouches were excised, fixed,
      and embedded in paraffin to be immunostained with proliferating cell nuclear
      antigen (PCNA). The results showed that increased PCNA expression was directly
      related to the severity of pathological alterations from normal epithelium to
      dysplasia and from dysplasia to squamous cell carcinoma (SCC) in the study groups
      at the different extended periods of DMBA application and S. platensis extract
      administration. Analysis of variance and Duncan's multiple-range test for PCNA
      labeling index were proved a high significant difference (P < 0.01) between the
      different groups. From the previous results, it can be concluded that S.
      platensis extract has a beneficial role in regression of cancer progression.

PMID- 19156552
TI  - Evidence based public health - the example of air pollution.
AB  - Evidence Based Medicine (EBM) has become a common paradigm in medicine. The
      notion that action should be based on scientific evidence also applies to public
      health. The assessment of evidence and the application of evidence based action
      is a challenge both in EBM and public health. The focus of this article is
      Evidence Based Public Health (EBPH). We use the issue of air pollution related
      health as an educational example for EBPH.

PMID- 19156554
TI  - Sodium deoxycholate causes nitric oxide mediated DNA damage in oesophageal cells.
AB  - Patients with chronic gastro-oesophageal reflux disease experience the reflux of
      acid and bile into the distal oesophagus. The secondary bile salt sodium
      deoxycholate (NDC) is implicated in the induction of mucosal injury during reflux
      episodes. This study hypothesized that NDC damages DNA in oesophageal cells by an
      oxidative mechanism. In the oesophageal cell line HET1-A, increased production of
      nitric oxide (NO) was measured in NDC-treated cells. Protection from DNA strand
      breaks induced by NDC (10 microm) was observed in cells coincubated with the
      nitric oxide scavenger C-PTIO (p<0.012) or pre-incubated with the NO synthase
      inhibitor L-NAME (p<0.009) or the NFkappaB inhibitor, TPCK (p<0.036).
      Collectively these data implicate the involvement of NFkappaB and nitric oxide
      synthase in the DNA damage induced by NDC in oesophageal cells. In conclusion,
      NDC-driven NO production may play an important role in inducing DNA damage during
      episodes of gastro-oesophageal reflux and thereby contribute to reflux-related
      carcinogenesis.

PMID- 19156555
TI  - A local-ingredient-based, processed flour to improve the energy, iron and zinc
      intakes of young children: a community-based intervention.
AB  - The present study was undertaken to determine the actual amounts of mush consumed
      and energy iron and zinc intakes of, and to investigate the attendance rate
      among, children aged 6-23 months due to an improved mush intervention. A cohort
      of 208 children from 27 villages was followed up for 6 months. Twice a day, 6
      days/week, each mother took her child to the nutrition centre we had opened in
      her village to receive the mush and fed it to her child. Amounts consumed were
      15, 21 and 33 g/kg body weight/meal for children aged 6-8, 9-11 and 12-23 months
      respectively. The average (standard deviation) attendance rate was 68.0% (25.6%).
      The median (range) daily intakes from the mush were 213 (25-373) kcal, 5.3 (0.6
      9.3) mg, and 2.3 (0.3-4.1) mg for energy, iron and zinc, respectively. This flour
      and mush production should enter the routines of individual households, supported
      by a large-scale programme of nutrition education.

PMID- 19156556
TI  - Framing ideas in aphasia: the need for thinking therapy.
AB  - This paper argues that some of the patterns seen in aphasia may reflect
      difficulties in the cognitive preparations for language. In particular, some
      individuals might be unable to carry out processes of 'Thinking for Speaking'
      (Slobin 1996), which frame thoughts for language production. Evidence to support
      this proposal is presented, together with signs that such thinking can be
      assisted with cues and therapy. It is argued that these preliminary data need to
      be pursued via a more comprehensive investigation of thinking therapy.

PMID- 19156553
TI  - Lupus-prone MRL/faslpr/lpr mice display increased AID expression and extensive
      DNA lesions, comprising deletions and insertions, in the immunoglobulin locus:
      concurrent upregulation of somatic hypermutation and class switch DNA
      recombination.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the
      production of an array of pathogenic autoantibodies, including high-affinity anti
      dsDNA IgG antibodies. These autoantibodies are mutated and class-switched, mainly
      to IgG, indicating that immunoglobulin (Ig) gene somatic hypermutation (SHM) and
      class switch DNA recombination (CSR) are important in their generation. Lupus
      prone MRL/fas(lpr/lpr) mice develop a systemic autoimmune syndrome that shares
      many features with human SLE. We found that Ig genes were heavily mutated in
      MRL/fas(lpr/lpr) mice and contained long stretches of DNA deletions and
      insertions. The spectrum of mutations in MRL/fas(lpr/lpr) B cells was
      significantly altered, including increased dG/dC transitions, increased targeting
      of the RGYW/WRCY mutational hotspot and the WGCW AID-targeting hotspot. We also
      showed that MRL/fas(lpr/lpr) greatly upregulated CSR, particularly to IgG2a and
      IgA in B cells of the spleen, lymph nodes and Peyer's patches. In
      MRL/fas(lpr/lpr) mice, the significant upregulation of SHM and CSR was associated
      with increased expression of activation-induced cytidine deaminase (AID), which
      mediates DNA lesion, the first step in SHM and CSR, and translesion DNA synthesis
      (TLS) polymerase (pol) theta, pol eta and pol zeta, which are involved in DNA
      synthesis/repair process associated with SHM and, possibly, CSR. Thus, in lupus
      prone MRL/fas(lpr/lpr) mice, SHM and CSR are upregulated, as a result of enhanced
      AID expression and, therefore, DNA lesions, and dysregulated DNA repair factors,
      including TLS polymerases, which are involved in the repair process of AID
      mediated DNA lesions.

PMID- 19156559
TI  - Performance-determining physiological factors in the luge start.
AB  - In luge, the start is a performance-determining factor. Athletes spend several
      months in the off-season training to improve starting performance. The aim of
      this study was to evaluate the influence of different physiological factors on
      the luge start and identify an appropriate physiological test battery. Thirteen
      male members of the Austrian national luge team were recruited. All participants
      completed a test battery that consisted of tests for balance, jumping, isometric
      truck flexion and extension strength, leg strength, hand grip strength, isometric
      bench pull and bench press strength, flexibility, and a luge start simulator.
      Regression analyses of fitness variables and starting speeds revealed
      relationships (P at least 0.049) except for flexibility, isometric trunk flexion
      strength, and isometric leg strength at a knee angle of 100 degrees (P at best
      0.069). Results showed that a single variable (isometric bench pull strength)
      explained most of the variance in maximum push-off speed (R2 = 0.750) and suggest
      that any test battery should include bench pull, trunk extension, and grip
      strength tests. Bench pull performance might also be a useful tool in the
      recruitment of athletes.

PMID- 19156560
TI  - Effects of different shoe-lacing patterns on the biomechanics of running shoes.
AB  - In the present study, we examined the influence of shoe lacing on foot
      biomechanics in running. Twenty experienced rearfoot runners ran in six different
      lacing conditions across a force platform at a speed of 3.3 m . s(-1). Foot
      pronation during contact, tibial acceleration, and plantar pressure distribution
      of the right leg were recorded. The test conditions differed in the number of
      laced eyelets (1, 2, 3, 6 or 7) and in lacing tightness (weak, regular or
      strong). The results show reduced loading rates (P < 0.05) and pronation
      velocities (P < 0.01) in the tightest and highest lacing conditions. The lowest
      peak pressures under the heel and lateral midfoot (P < 0.01) were observed in the
      high (seven-eyelet) lacing pattern. Regular six-eyelet cross-lacing resulted in
      higher loading rates (P < 0.05) and higher peak heel pressures (P < 0.01) than
      seven-eyelet lacing, without any significant differences in perceived comfort.
      The low lace shoe conditions resulted in lower impacts (P < 0.01) and lower peak
      pressures under metatarsal heads III and V (P < 0.01), which is probably induced
      by the foot sliding within the shoe. A firm foot-to-shoe coupling with higher
      lacing leads to a more effective use of running shoe features and is likely to
      reduce the risk of lower limb injury.

PMID- 19156561
TI  - Strapping rowers to their sliding seat improves performance during the start of
      ergometer rowing.
AB  - Rowers sit on a seat that slides relative to the boat/ergometer. If a rower lifts
      him or herself from this sliding seat at any time, the seat will move away from
      under them and the rowing action is disrupted. From a mechanical perspective, it
      is clear that the need for the rower to remain in contact with the sliding seat
      at all times imposes position-dependent constraints on the forces exerted at the
      oar handle and the footstretcher. Here we investigate if the mechanical power
      output during rowing, which is strongly related to these forces, might be
      improved if the contact with the sliding seat was of no concern to the rower. In
      particular, we examine if elimination of these constraints by strapping the rower
      to the sliding seat leads to an increase in performance during the start on a
      standard rowing ergometer. Eleven well-trained female rowers performed 5-stroke
      starts in normal and strapped conditions. Handle force, vertical seat force,
      footstretcher force, and handle kinematics were recorded, from which mechanical
      power and work output were calculated. Most of the relevant mechanical variables
      differed significantly between the normal and strapped conditions. Most
      importantly, mechanical power output (averaged over the 5-stroke start) in the
      strapped condition was 12% higher than in the normal condition. We conclude that
      strapping a rower's pelvis to the sliding seat allows more vigorous execution of
      the stroke phases, resulting in a substantial improvement in performance during
      the start of ergometer rowing.

PMID- 19156562
TI  - Whole-body efficiency is negatively correlated with minimum torque per duty cycle
      in trained cyclists.
AB  - The purpose of this study was to determine whether there is a causal relationship
      between pedalling "circularity" and cycling efficiency. Eleven trained cyclists
      were studied during submaximal cycling. Variables recorded included gross and
      delta efficiency and the ratio of minimum to peak torque during a duty cycle.
      Participants also completed a questionnaire about their training history. The
      most notable results were as follows: gross efficiency (r = -0.72, P < 0.05 at
      250 W) was inversely correlated with the ratio of minimum to peak torque,
      particularly at higher work rates. There was a highly significant inverse
      correlation between delta efficiency and average minimum torque at 200 W (r = 
      0.76, P < 0.01). Cycling experience was positively correlated with delta
      efficiency and gross efficiency, although experience and the ratio of minimum to
      peak torque were not related. These results show that variations in pedalling
      technique may account for a large proportion of the variation in efficiency in
      trained cyclists. However, it is also possible that some underlying physiological
      factor influences both. Finally, it appears that experience positively influences
      efficiency, although the mechanism by which this occurs remains unclear.

PMID- 19156563
TI  - Burnout assessment in house officers: evaluation of an intervention to reduce
      stress.
AB  - BACKGROUND: Medical house officers are at increased risk for stress related
      symptoms leading to professional burnout. AIMS: Measure burnout in house officers
      and establish whether utilization of a psychotherapeutic tool individually by
      physicians reduces symptoms characteristic of burnout. METHOD: Two groups of
      pediatric house officers at the University of California Davis Health System
      completed a Maslach Burnout Survey (MBS) at the beginning and end of a three
      month period in 2003. An Intervention group (7 of 15 enrolled) was trained in the
      use of a self-administered psychotherapeutic tool. Outcome Measures were MBS
      scores and a qualitative interview of intervention group members. RESULTS: There
      were no significant differences between the two groups, prior to the study or
      over time. Qualitative interviews revealed that subjects experience stressors in
      relation to their professional activities, but already utilize some elements of
      the tool and were too busy to implement the entire tool systematically.
      CONCLUSIONS: Pediatric trainees did not seem to manifest burnout symptoms based
      upon the MBS; interviews suggested that some do experience significant stress,
      although manifestations and responses were varied, some may be at risk. Methods
      identifying individuals at risk for burnout, and interventions to cope with
      stress may be valuable to their training.

PMID- 19156564
TI  - Autobiographical memory after acute stress in healthy young men.
AB  - Autobiographical memories have been found to be less specific after
      hydrocortisone administration in healthy men, resembling memory deficits in, for
      example, depression. This is the first study to investigate the effects of stress
      induced elevated cortisol levels on autobiographic memory specificity and
      experience in healthy young men. Autobiographical memories were elicited by
      neutral and negative cue words, with instructions to recall either recent or
      remote memories. No effect of psychosocial stress was found on memory specificity
      or experience, but cortisol increases tended to be related to less specific,
      recent memories elicited by neutral cue words, especially when participants were
      physically aroused during memory retrieval. These results indicate that
      autobiographical memories are fairly resistant to an acute stressor in healthy
      young men, but that endogenous cortisol increases might be related to
      autobiographical memory retrieval. More research into the relation between
      endogenous cortisol increases and autobiographic memory retrieval is needed,
      especially in stress-related disorders.

PMID- 19156565
TI  - Don't it make my brown eyes blue: co-witness misinformation about a target's
      appearance can impair target-absent line-up performance.
AB  - Misinformation from another witness has been shown to impair eyewitness reports,
      but little is known about how it may influence eyewitness identification. In
      Experiment 1, adult pairs comprising one participant and one experimental
      confederate viewed a video clip of a staged theft. Half of the participants were
      then misinformed by the confederate that the thief's accomplice had blue eyes (in
      fact, they were brown). Next, individual participants described the accomplice
      and completed a target-absent photographic line-up task comprising blue-eyed
      members. Misinformed participants were several times more likely than controls to
      describe the accomplice as having blue eyes, and twice as likely to identify
      someone from the line-up. In Experiment 2, when line-up members' eye colour was
      digitally altered from blue to brown, the line-up effect disappeared, suggesting
      that the increase in identifications in Experiment 1 was not a generalised
      increase in willingness to choose from the line-up. In Experiment 3, we
      discounted the possibility that discussion alone could account for the line-up
      misinformation effect, by subjecting all participants to co-witness discussion.

PMID- 19156567
TI  - The association of thyroid immunity with blood pressure and body mass index in
      primary care patients.
AB  - OBJECTIVES: To evaluate the association of thyroid immunity with cardiovascular
      symptoms and body mass index (BMI). METHODS: Four hundred and sixty-five primary
      care patients underwent ultrasound evaluation of the thyroid gland, with hypo
      echoic thyroid pattern indicating autoimmune involvement. BMI and blood pressure
      (BP) were the main outcomes. RESULTS: Men and women with hypo-echoic thyroid had
      higher BMI and higher BP in comparison to patients with normo-echoic thyroid.
      Among women with hypo-echoic thyroid, only those who were premenopausal had
      higher BMI and higher BP in comparison to women with normo-echoic thyroid.
      CONCLUSIONS: Thyroid immunity is related to higher BMI and higher BP in men and
      women, especially in premenopausal women.

PMID- 19156566
TI  - Cognitive function in breast cancer survivors compared to healthy age- and
      education-matched women.
AB  - The cognitive function of breast cancer survivors (BC, n = 52) and individually
      matched healthy controls (n = 52) was compared on a battery of sensitive
      neuropsychological tests. The BC group endorsed significantly higher levels of
      subjective memory loss and scored significantly worse than controls on learning
      and delayed recall indices from the Rey Auditory Verbal Learning Test (AVLT).
      Defining clinically significant impairment as scores at or below the 7th
      percentile of the control group, the rate of cognitive impairment in the BC
      sample was 17% for total learning on the AVLT, 17% for delayed recall on the
      AVLT, and 25% for either measure. Findings indicate that a sizeable percentage of
      breast cancer survivors have clinically significant cognitive impairment.

PMID- 19156568
TI  - Absence of an opioid stimulatory tone on growth hormone secretion in women with
      microprolactinoma.
AB  - INTRODUCTION: Literature data suggest that prolactinoma is a tumor with a complex
      pathogenesis and that its growth is the result of changes at the pituitary and/or
      hypothalamic level. Abnormal release of hypothalamic factors (including
      endogenous opioid peptides) may contribute to prolactinoma development. An
      increased endogenous opioid tone (EOT) occurs in patients with prolactinoma, and
      seems to play an important role in pituitary secretion, as suggested by the
      ability of the opiate receptor antagonist naloxone to stimulate luteinizing
      hormone pulsatile secretion in these patients. OBJECTIVE: To investigate the
      effect of the EOT on growth hormone (GH) secretion in women with prolactinoma.
      DESIGN: Eleven women aged 30.4+/-6.7 years (range 20-41), with an established
      diagnosis of microprolactinoma, were studied. GH-releasing hormone (GHRH), 100
      microg as an intravenous (i.v.) bolus, was administered with and without
      preadministration of i.v. naloxone, an opioid receptor antagonist, 2 mg as a
      bolus followed by a constant infusion of 1.6 mg/h. Blood samples were taken for
      120 min after GHRH administration. RESULTS: Naloxone did not affect the GH
      response to GHRH, measured as single times, mean peak values, or as integrated
      concentrations. CONCLUSION: Our data suggest that an opioid stimulatory tone on
      GH secretion in women with prolactinoma is absent.

PMID- 19156569
TI  - Malignant transformation of mammary epithelial cells increases expression of
      leptin and leptin receptor.
AB  - Both normal and malignant mammary tissues have been shown to produce leptin and
      express leptin receptors. This study compared the expression of leptin and leptin
      receptor mRNA in a variety of normal and malignant mammary epithelial cell lines
      and observed that in general the malignant lines expressed higher levels of
      leptin and leptin receptor mRNA than nonmalignant lines. Furthermore, oncogenic
      transformation of nonmalignant cell lines increased expression of leptin and
      leptin receptor, with expression of ErbB2 giving particularly high levels of
      expression of long-form leptin receptor. In addition, nonmalignant cells
      exhibited little or no increase in DNA synthesis following leptin treatment,
      whereas oncogene-transformed cells had increased DNA synthesis in response to
      leptin. These effects varied among oncogenes, with ErbB2-transformed cells
      showing particularly high expression of leptin receptor mRNA and high response to
      leptin.

PMID- 19156570
TI  - Adrenomedullary and glycemic alterations following diverse stress in soft-shelled
      turtles Lissemys punctata punctata Bonnoterre.
AB  - The objective of the current investigation was to study adrenomedullary and
      glycemic responses to stress in soft-shelled turtles, Lissemys p. punctata.
      Dehydration (7 days) and formalin (formaldehyde 1%, 0.1 mL/100 g body wt. daily
      for 7 days) stress-stimulated adrenomedullary activity at histological (by
      increasing the nuclear diameter and degranulation of chromaffin cells) and
      hormonal levels (by elevations of norepinephrine and epinephrine concentrations)
      with hyperglycemia in turtles. But salt loading (NaCl: 1%, 1 mL/100 g body wt.
      daily for 7 days) had no significant effect on adrenomedullary activity or
      glycemia presumably owing to the nonresponsiveness of adrenocortical activity to
      salt stress in turtles. It is suggested that dehydration and formalin stresses
      might have exerted their actions through the hypothalamo (CRF)-hypophysial (ACTH)
      adrenocortical axis in turtles.

PMID- 19156571
TI  - Descriptive epidemiology of type 1 diabetes in youth: incidence, mortality,
      prevalence, and secular trends.

PMID- 19156572
TI  - Natural evolution, prediction, and prevention of type 1 diabetes in youth.

PMID- 19156573
TI  - Epidemiology of type 2 diabetes in children and adolescents.

PMID- 19156574
TI  - Obesity and T2DM in youth.

PMID- 19156575
TI  - Prevention and screening for type 2 diabetes in youth.

PMID- 19156576
TI  - A polymerase chain reaction-coupled high-resolution melting curve analytical
      approach for the monitoring of monospecificity of avian Eimeria species.
AB  - Coccidiosis is a significant disease of poultry caused by different species of
      Eimeria. Differentiation of Eimeria species is important for the quality control
      of the live attenuated Eimeria vaccines derived from monospecific lines of
      Eimeria spp. In this study, high-resolution melting (HRM) curve analysis of the
      amplicons generated from the second internal transcribed spacer of nuclear
      ribosomal DNA (ITS-2) was used to distinguish between seven pathogenic Eimeria
      species of chickens, and the results were compared with those obtained from the
      previously described technique, capillary electrophoresis. Using a series of
      known monospecific lines of Eimeria species, HRM curve analysis was shown to
      distinguish between Eimeria acervulina, Eimeria brunetti, Eimeria maxima, Eimeria
      mitis, Eimeria necatrix, Eimeria praecox and Eimeria tenella. Computerized
      analysis of the HRM curves and capillary electrophoresis profiles could detect
      the dominant species in several specimens containing different ratios of E.
      necatrix and E. maxima and of E. tenella and E. acervulina. The HRM curve
      analysis identified all of the mixtures as "variation" to the reference species,
      and also identified the minor species in some mixtures. Computerized HRM curve
      analysis also detected impurities in 21 possible different combinations of the
      seven Eimeria species. The PCR-based HRM curve analysis of the ITS-2 provides a
      powerful tool for the detection and identification of pure Eimeria species. The
      HRM curve analysis could also be used as a rapid tool in the quality assurance of
      Eimeria vaccine production to confirm the purity of the monospecific cell lines.
      The HRM curve analysis is rapid and reliable and can be performed in a single
      test tube in less than 3 h.

PMID- 19156577
TI  - Identification of chicken enterovirus-like viruses, duck hepatitis virus type 2
      and duck hepatitis virus type 3 as astroviruses.
AB  - Earlier work identified and biologically characterized antigenically distinct
      enterovirus-like viruses (ELVs) of chickens. Three of these ELVs can now be
      identified as astroviruses. Characterization involved the use of a hitherto
      undescribed, degenerate primer-based reverse transcription-polymerase chain
      reaction (RT-PCR) to amplify astrovirus open reading frame (ORF) 1b-specific cDNA
      fragments followed by nucleotide sequence determination and analysis of the
      amplified fragments. ELV-1 was confirmed as an isolate of the astrovirus avian
      nephritis virus (ANV). ELV-4 (isolate 612) and ELV-3 (isolates FP3 and 11672)
      were antigenically and genetically related to the second characterized astrovirus
      of chickens, namely chicken astrovirus (CAstV). Using indirect
      immunofluorescence, the FP3 and 11672 ELV-3 isolates were very closely related to
      one another, and less closely related to ELV-4 and the previously described CAstV
      (P22 18.8.00 reference isolate). Comparative analyses based on the ORF 1b
      amplicon sequences showed that the FP3 and 11672 ELV-3 isolates shared high
      nucleotide (95%) and amino acid (98%) identities with one another, and lower
      nucleotide (76% to 79%) and amino acid (84% to 85%) identity levels with ELV-4
      and the reference CAstV P22 18.8.00 isolates. The combined degenerate primer RT
      PCR and sequencing methods also provided a nucleotide sequence specific to duck
      hepatitis virus type 2 (DHV-2) (renamed duck astrovirus) and duck hepatitis virus
      type 3 (DHV-3), which, for the first time, can also be identified as an
      astrovirus. Phylogenetic analyses based on the amplified ORF 1b sequences showed
      that ANV was the most distantly related avian astrovirus, with DHV-3 being more
      closely related to turkey astrovirus type 2 than DHV-2.

PMID- 19156578
TI  - Comparative analysis of the sialic acid binding activity and the tropism for the
      respiratory epithelium of four different strains of avian infectious bronchitis
      virus.
AB  - Avian infectious bronchitis virus (IBV) is a major pathogen in commercial poultry
      flocks. We recently demonstrated that sialic acid serves as a receptor
      determinant for IBV on the tracheal epithelium. Here we compared the IBV strains
      Beaudette, 4/91, Italy02, and QX for their sialic acid-binding properties. We
      demonstrate that sialic acid binding is important for the infection of primary
      chicken kidney cells and the tracheal epithelium by all four strains. There were
      only slight differences between the four strains, indicating the universal usage
      of sialic acids as receptor determinants by IBV. In addition, we analysed the
      primary target cells in the respiratory epithelium of the four different strains
      and found that all of them infected ciliated cells and goblet cells.

PMID- 19156579
TI  - Pathogenicity and growth characteristics of selected infectious laryngotracheitis
      virus strains from the United States.
AB  - In a recent study, several US infectious laryngotracheitis virus (ILTV) strains
      and field isolates were genotyped by polymerase chain reaction and restriction
      fragment length polymorphism (PCR-RFLP) into nine different genotypes. All of the
      commercial poultry isolates were identified within genotypes IV, V, and VI. Based
      on the PCR-RFLP, Group IV isolates were characterized as genetically identical to
      the chicken embryo origin (CEO) vaccines, Group V as genetically closely related
      to the CEO vaccines, and Group VI as genetically different to the vaccine
      strains. The objective of this study was to determine the pathogenicity and
      growth characteristics of six ILTV commercial poultry isolates as compared with
      the CEO vaccine. Two isolates representative of PCR-RFLP Groups IV, V, and VI
      were selected. Differences in disease severity, viral tissue distribution in
      chickens, and plaque formation ability in cell culture were observed among viral
      genotypes IV, V, and VI, and between V-A and V-B isolates. Mild respiratory
      clinical signs were produced by IV-A, IV-B and the CEO vaccine, while VI-A and VI
      B isolates produced severe respiratory signs and severe depression, and during
      the peak of clinical signs both isolates were re-isolated from the conjunctiva,
      sinus, trachea and thymus. Similarly to Group VI isolates, V-A and V-B produced
      severe respiratory signs, depression, and were re-isolated from conjunctiva,
      sinus, and trachea; on cell culture, both isolates produced significant larger
      plaques than any of the other isolates analysed. Overall, differences in
      pathogenicity and growth characteristics were observed among genetically closely
      related US ILTV isolates; however, complete genomes will be necessary to identify
      molecular determinants linked to the pathogenic viral phenotypes.

PMID- 19156580
TI  - Endocarditis due to Lactobacillus jensenii in a Salvin's Amazon parrot (Amazona
      autumnalis salvini).
AB  - A 30-year-old Salvin's Amazon parrot (Amazona autumnalis salvini) with a history
      of a lifelong poor diet and inappropriate housing was presented in lateral
      recumbency to a veterinary teaching hospital for further evaluation. Radiological
      and ultrasonographic examination revealed a mild proventricular dilatation, mild
      hepatomegaly, signs of enteritis and airsacculitis. The main laboratory findings
      included a mild macrocytic hyperchromic anaemia, hypoglobulinaemia, decreased
      bile acids and increased alkaline phosphatase. In this bird a liver pathology was
      suspected because of the clinical, laboratory and ultrasonographic findings. The
      bird was treated with supportive care and metabolic aids. After initial
      improvement of the clinical signs, the bird's condition deteriorated and it died.
      Pathological findings revealed an endocarditis and myocarditis due to
      Lactobacillus jensenii and a bacteraemia. Endocarditis due to Lactobacillus sp.
      is a rare phenomenon in humans not yet described in animals. It is associated
      with severe underlying illnesses leading to translocation of otherwise non
      pathogenic bacteria in the bloodstream. A similar pattern might be assumed in
      animals with compromised immunity.

PMID- 19156581
TI  - Transmission of low-pathogenicity avian influenza virus of subtype H6N2 from
      chickens to Pekin ducks and Japanese quail (Coturnix coturnix japonica).
AB  - In this experiment we evaluated the transmission characteristics of a chicken
      adapted low-pathogenicity avian influenza virus (LPAIV) of subtype H6N2, from
      infected chickens to Japanese quail and Pekin ducks, which are commonly sold in
      live bird markets located in Southern California. The layout of the cages and
      bird-handling practices were similar to those found in Southern California live
      bird markets. Five out of 20 chickens were inoculated with LPAIV H6N2, and placed
      in direct contact with five chickens and in indirect contact with 10 chickens, 10
      Japanese quail and 10 Pekin ducks. Transmission of LPAIV was followed in each
      bird daily for 15 days post inoculation by real-time reverse transcriptase
      polymerase chain reaction testing of oropharyngeal and cloacal swab samples. This
      strain of H6N2 LPAIV, isolated from commercial poultry in California, was
      transmitted to chickens, quail, and ducks from chickens. An antibody response was
      detected in ducks by haemagglutination inhibition tests, but avian influenza
      virus was only detected by reverse transcriptase-polymerase chain reaction in one
      duck. Avian influenza virus was detected in quail (5 and 7 days post inoculation)
      before chickens (8 and 9 days post inoculation), all of which were in indirect
      contact with infected chickens; however, this difference was not statistically
      significant.

PMID- 19156582
TI  - Cutaneous form of pox infection among captive peafowl (Pavo cristatus) chicks.
AB  - The present study was carried out to investigate the epidemiology and lesions of
      avian pox in captive peafowl chicks. Overall values of morbidity, mortality and
      case fatality were 45.2%, 27.1% and 60.0%, respectively. The chicks of 9 to 12
      weeks of age showed a significantly (P<0.001) higher prevalence rate than other
      age groups. The morbidity and mortality due to avian pox in peafowl chicks was
      significantly (P<0.001) reduced when kept in mosquito-proof cages and hatched
      under broody chicken hens. Morbidity due to poxvirus infection on the peafowl
      farm was 82%, 26% and 12% in successive years. This reduction might have been the
      result of the introduction of mosquito-proof nets after year 1, although this was
      not the subject of a controlled experiment. All of the peafowl chicks suffering
      from dry pox showed pustular and nodular lesions on eye lids, beak, legs and
      toes. Distribution of lesions in different body parts varied significantly
      (P<0.023). Lesion diameters were less than 1 cm (59.73%), 1 to 2 cm (23.75%) and
      more than 2 cm (16.87%). Histopathological studies revealed extensive
      proliferation of subdermal connective tissue and infiltration of heterophils and
      macrophages. The keratinocytes showed degenerative changes in the form of
      cytoplasmic vacuolation, ballooning and hyper-chromatic nuclei. Eosinophilic
      intracytoplasmic inclusions (Bollinger bodies) in keratinocytes were consistently
      present. It was concluded that avian pox rendered high morbidity, mortality and
      case fatality in peafowl chicks.

PMID- 19156583
TI  - Passive immunization against Histomonas meleagridis does not protect turkeys from
      an experimental infection.
AB  - Histomonosis or blackhead is a disease of gallinaceous birds, caused by the
      protozoan Histomonas meleagridis. As recent regulatory action has removed almost
      all drugs against this disease from the European market, the development of new
      prophylactics has become crucial. Identification of the protective immune
      mechanism would facilitate the choice and development of a vaccination strategy
      to prevent histomonosis. In this study, turkeys were either actively or passively
      immunized and were then challenged to assess the role of antibody-mediated
      immunity in the protection form this disease. Active immunization was performed
      either by experimental infection and treatment or by intramuscular injection with
      lysed H. meleagridis. Passive immunization was attempted by intraperitoneal
      administration of pooled, concentrated, neutralizing antisera from immunized
      donor animals to naive turkeys. A significantly higher IgG response was observed
      after infection and treatment than after intramuscular injection, which in turn
      was higher than the responses of placebo and control birds. While active
      immunization of turkeys by intramuscular injection of dead H. meleagridis
      antigens appeared not to be protective against histomonosis, immunization by
      infection and treatment did induce protection. However, no significant level of
      protection could be observed in the passively immunized birds. These results
      suggest that serum antibodies to H. meleagridis may not be a key component in the
      protection against this parasite. It is, however, possible that the concentration
      of antibodies at the mucosal site is insufficient. Therefore, further
      investigation on mucosal immune responses is necessary.

PMID- 19156584
TI  - Induction of eggshell apex abnormalities by Mycoplasma synoviae: field and
      experimental studies.
AB  - A novel eggshell pathology, characterized by an altered shell surface, thinning,
      increased translucency, and cracks and breaks in the eggshell apex, has become
      increasingly common in layer flocks of various breeds in The Netherlands. Two
      field studies found an association between the eggshell apex abnormalities (EAA)
      and infection with Mycoplasma synoviae. M. synoviae was isolated from the oviduct
      of birds that produced abnormal eggs, but not from birds in control flocks,
      although both affected and control birds had agglutinating antibodies against M.
      synoviae. After a single injection with long-acting oxytetracycline, the
      production of abnormal eggs ceased, but then reoccurred about 12 days later. A
      causal relationship between EAA and M. synoviae infection was subsequently
      demonstrated experimentally. EAA occurred after intratracheal inoculation of
      birds with M. synoviae, and even more frequently in birds infected with
      infectious bronchitis virus 5 days before inoculation of M. synoviae. EAA also
      occurred, although less frequently, in birds inoculated intravenously with M.
      synoviae and infected with infectious bronchitis virus. EAA did not occur in
      birds only inoculated intravenously with M. synoviae. M. synoviae was only
      isolated from the oviducts of birds producing abnormal eggs. The mean daily egg
      production was reduced in all groups infected with M. synoviae. Examination of
      the eggshells by scanning electron microscopy revealed that the mammillary layer
      of the calcified zone was absent and that the inner eggshell membranes were
      thicker. Isolates of M. synoviae from the oviducts of birds from farms producing
      abnormal eggs were examined by amplified fragment-length polymorphism analysis
      and did not appear to be clonal.

PMID- 19156586
TI  - The role of DHEA-S in the mood adjustment against negative competition outcome in
      golfers.
AB  - Several lines of evidence suggest that dehydroepiandrosterone sulphate (DHEA-S)
      is invariably consumed following different types of acute stress, implicating its
      role in stress coping and recovery. The role of DHEA-S in the mood adjustment
      against negative outcome for athletic competition has not previously been
      investigated. In the current study, 14 elite golfers participating in a major
      national golf tournament were subsequently divided into two groups according to
      their competition outcomes: made the cut (n=8) and failed to make the cut (n 8).
      The Profile of Mood States (POMS) inventory and plasma concentrations of DHEA-S
      and cortisol were measured 1 day before the beginning of competition (baseline)
      and 1, 3, and 5 days after the players' final competition, in the morning (08.00
      08.30 h) under fasted conditions. Results showed that the total mood disturbance
      scores and DHEA-S were not changed for the group that made the cut throughout the
      entire observation period. DHEA-S concentration for the group that failed to make
      the cut fell significantly below baseline values on day 1 and remained lower for
      5 days. The Depression subscale of the POMS for the group that failed to make the
      cut was increased only on day 1 post-competition, reflecting a situational
      reaction to the event. Cortisol concentration for the group that made the cut
      fell significantly below baseline values on day 1 only after competition and no
      change was observed for the group that failed to make the cut. In conclusion,
      although the overall mood state post-competition was well-maintained for those
      golfers who had a negative competition outcome, plasma DHEA-S concentration was
      reduced for 5 days, suggesting that it has a role in the coping mechanism against
      psychological challenge.

PMID- 19156587
TI  - [The rise of hepato-oncology].

PMID- 19156589
TI  - Long-term treatment of advanced hepatocellular carcinoma with the tyrosine kinase
      inhibitor erlotinib (Tarceva)--a case report.
AB  - AIM: Hepatocellular carcinoma (HCC) is the 5th most common human malignancy with
      an increasing incidence in western countries and still unsatisfactory median
      survival rates of 5 - 7 months. Currently, new treatments with biologicals (so
      called "targed therapies") such as VEGF and EGF antibodies or tyrosine kinase
      inhibitors (e. g., sorafenib) are being tested in patients with HCC. Here we
      report a long-term treatment of an advanced, multifocal HCC with the tyrosine
      kinase inhibitor erlotinib (Tarceva). PATIENT AND METHODS: A 64-year-old man with
      newly diagnosed and histologically proven advanced HCC and hydropic liver
      cirrhosis (Child-Pugh B) was treated for 18 months (12 / 05 - 06 / 07) with
      erlotinib. In addition paracentesis was performed every 6 weeks to provide relief
      from ascites. RESULTS: After 2 weeks of treatment with 100 mg erlotinib QD the
      patient developed a 3 degrees-4 degrees skin toxicity (haemorrhagic rush). Other
      major side effects did not occur. Erlotinib medication was stopped for 2 weeks
      and re-started at a reduced dose of 75 mg QD. Marker tumour lesions (No. 1:
      caudate lobe/No. 2: segment III), liver enzymes and synthesis parameters
      (albumin, prothrombin time/INR) and frequency of paracentesis remained stable
      during the 18 months of observation. CONCLUSIONS: Erlotinib (Tarceva) appears to
      be an interesting treatment option for patients with advanced HCC. More clinical
      data and studies are needed to confirm this result.

PMID- 19156588
TI  - Terlipressin in 30 patients with hepatorenal syndrome: results of a retrospective
      study.
AB  - Terlipressin is known to improve renal function in patients with liver cirrhosis
      and hepatorenal syndrome (HRS). This study investigated effects of duration and
      dose of terlipressin therapy and predictive factors for positive response to
      treatment. The clinical charts of 30 consecutive patients with HRS who received
      terlipressin and albumin based on a determined therapeutic scheme, were
      retrospectively studied. In 25 (66 %) of 38 treatment episodes complete response
      was achieved (Kaplan-Meier survival method). Predictive for positive response to
      treatment were duration of treatment and cumulative terlipressin dosis (p < 0.01,
      95 % CI 0.31 - 0.59 and p < 0.01, 95 % CI 0.93 - 0.98, respectively) as well as a
      low level of serum creatinine and MELD score at inclusion (p = 0.01, 95 % CI 0.3 
      9.85 and p < 0.01, 95 % CI 0.87 - 0.98 respectively) and HRS type II (p = 0.04,
      95 % CI 1.04 - 9.93). The median duration of therapy was 6 days +/- 4.9 (SD) vs.
      8 days +/- 6.3 in the nonresponder group. The median dose of terlipressin in the
      responder group was 3.9 mg +/- 1.3 per day vs. 3.4 mg +/- 1.4 in the nonresponder
      group (p = n. s.). The probability that complete response was obtained at day 17
      of treatment was 84 % (95 % CI 0.64 - 0.96), whereas at day 7 it was just 52 %
      (95 % CI 0.36 - 0.7). In conclusion, these data confirm that terlipressin plus
      albumin is effective in two-thirds of patients with HRS. Prolongation of
      treatment beyond 7 days up to 20 days is capable of increasing the response
      rates. Whether outcome can be predicted depending on parameters like type of HRS
      and base-level of serum creatinine needs to be confirmed in further studies,
      especially with regard on the previously revised criteria of HRS.

PMID- 19156590
TI  - [Recent developments in biopsy diagnosis of early and undefined liver tumors].
AB  - Biopsy diagnosis of early and highly differentiated liver tumors is difficult and
      complex. Modern pathology has met this challenge by several different means;
      elaborate morphological algorithms and novel immunohistological markers support
      the differential diagnosis of highly differentiated HCC and a new, predictive
      molecular pathological and histological classification of liver cell adenoma was
      developed. By these new diagnostic tools together with the so-called 'matrix
      diagnosis' a reliable diagnostic classification is now feasible in the vast
      majority of these difficult cases.

PMID- 19156591
TI  - [Selective internal radiotherapy (radioembolization) and radiation therapy for
      HCC--current status and perspectives].
AB  - Microsphere and particle technologies for the selective transport of tumoricidal
      agents or radiation represent a new generation of therapeutics in interventional
      oncology. The intrahepatic application of radioactive microspheres via the
      hepatic artery, for instance, allows locoregional therapy of diffuse or
      multifocal liver tumours, for which to date systemic therapy was the only
      remaining option. Current standards for this selective internal radiotherapy or
      radioembolisation are 90-yttrium glass or resin microspheres. Indication,
      technique, and the current results are extensively discussed. In addition to 90
      yttrium microspheres, other radiopharmaceuticals, such as 131-iodine or 188
      rhenium lipiodol, have been successful used for SIRT. As a result of new, more
      selective radiation techniques, internal radiotherapy for the locoregional
      treatment of HCC has been recently complemented by an increasing use of
      percutaneous radiotherapy.

PMID- 19156592
TI  - [Sorafenib for the treatment of HCC--the beginning of a new era in the treatment
      of HCC].
AB  - Sorafenib increases overall survival in patients with advanced HCC by almost
      three months. However, despite these advances in the treatment of patients with
      HCC, average overall survival remains below one year. Based on our understanding
      of hepatocarcinogenesis, the development of new molecular targeting agents and
      results from biomarker studies in HCC, new therapeutic treatment options are
      currently being investigated. We summarize recent results on the molecular
      therapy for HCC and discuss how these can be efficiently tested in patients with
      HCC.

PMID- 19156593
TI  - [New surgical approaches in the treatment of hepatocellular carcinoma].
AB  - New advances in the treatment of HCC have emerged in recent years. The
      implementation of surveillance programmes has led to better diagnosis of HCC at
      early stages. Liver resection and liver transplantation remain the only
      potentially curative treatment options that can be applied in a limited number of
      patients resulting in 5-year survival rates as high as 75 - 80 %. Resection is
      indicated in patients with limited disease and absence of cirrhosis. Liver
      transplantation is beneficial in patients with cirrhosis and tumour size
      according to the Milan criteria. Organ donor shortage and the consequently long
      waiting time limits its applicability. TACE and radiofrequency ablation provide
      local tumour control in unresectable HCC and are increasingly used in addition to
      tumour resection. The major drawback of all treatments is the risk for local
      tumour recurrence or tumour progress during the waiting time for transplantation.
      The application of sorafenib in the (neo-)adjuvant situation is being tested in
      clinical trials.

PMID- 19156594
TI  - [S3-guideline "Helicobacter pylori and gastroduodenal ulcer disease"].
AB  - This guideline updates a prior concensus recommendation of the German Society for
      Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an
      interdisciplinary cooperation with representatives of the German Society for
      Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE) and
      the German Society for Rheumatology. The guideline is methodologically based on
      recommendations of the Association of the Scientific Medical Societies in Germany
      (AWMF) for providing a systematic evidence-based consensus guideline of S 3 level
      and has also implemented grading criteria according to GRADE (Grading of
      Recommendations Assessment, Development and Evaluation). Clinical applicability
      of study results as well as specifics for Germany in terms of epidemiology,
      antibiotic resistance status, diagnostics and therapy were taken into account.

PMID- 19156598
TI  - Menthol and geraniol biotransformation and glycosylation capacity of Levisticum
      officinale hairy roots.
AB  - The biotransformation capacity of Levisticum officinale W.D.J. Koch hairy root
      cultures was studied by evaluating the effect of the addition of 25 mg/L menthol
      or geraniol on morphology, growth, and volatiles production. L. officinale hairy
      root cultures were maintained for 7 weeks in SH medium, in darkness at 24 degrees
      C and 80 r.p.m., and the substrates were added 15 days after inoculation. Growth
      was evaluated by measuring fresh and dry weight and by using the dissimilation
      method. Volatiles composition was analyzed by GC and GC-MS. Hairy roots
      morphology and growth were not influenced by substrate addition. No new volatiles
      were detected after menthol addition and, as was also the case with the control
      cultures, volatiles of these hairy roots were dominated by (Z)-falcarinol (1
      45%), N-octanal (3-8%), palmitic acid (3-10%), and (Z)-ligustilide (2-9%). The
      addition of geraniol induced the production of six new volatiles:
      nerol/citronellol/neral (traces-15%), alpha-terpineol (0.2-3%), linalool (0.1
      1.2%), and geranyl acetate (traces-2%). The relative amounts of the substrates
      and some of their biotransformation products decreased during the course of the
      experiment. Following the addition of beta-glycosidase to the remaining
      distillation water, analysis of the extracted volatiles showed that lovage hairy
      roots were able to convert both substrates and their biotransformation products
      into glycosidic forms. GC:gas chromatography GC-MS:gas chromatography-mass
      spectrometry SH:Schenk and Hildebrandt (1972) culture medium.

PMID- 19156599
TI  - Cytotoxic terpenoids from the fruits of Vitex trifolia L.
AB  - Two new labdane-type diterpenoids vitetrifolin H (1) and vitetrifolin I (2), and
      one new monoterpenoid vitexoid (3), were isolated from the fruits of Vitex
      trifolia L., together with seven known diterpenoids. Structures of all compounds
      were elucidated by extensive spectroscopic methods. All these compounds exhibited
      inhibition of Hela cell proliferation, with IC50 values in the range of 4-28
      microM. In addition, vitetrifolin I (2) induced cell cycle G0/G1 phase arrest and
      apoptosis of Hela cells.

PMID- 19156600
TI  - [Detection of Cryptosporidium spp. in feces with nested PCR and carbol fuchsin
      staining method].
AB  - This study was carried out on 45 stool specimens, consisting of 18 samples from
      children with diarrhea and 27 samples from diarrheic calves. Samples were
      screened by both carbol fuchsin staining and nested PCR for presence of
      Cryptosporidium spp. Using the carbol fuchsin staining method, we detected a
      total of 4 (8.9%) positive samples out of 45; of these 3 (11.2%) were from calf
      samples and 1 (5.6%) from a child. Nested PCR detected a total of 9 (20.0%
      positive samples out of 45 including 8 (29.7%) from calf samples and 1 (5.6%)
      from a child. Although the staining method revealed a 100% specificity, it was
      deficient in sensitivity (44.0%) compared to nested PCR. The study showed that
      nested PCR is an acceptable method for studying the etiology of doubtful
      diarrheal cases.

PMID- 19156597
TI  - The contribution of psychosocial stress to the obesity epidemic: an evolutionary
      approach.
AB  - The Thrifty Gene hypothesis theorizes that during evolution a set of genes has
      been selected to ensure survival in environments with limited food supply and
      marked seasonality. Contemporary environments have predictable and unlimited food
      availability, an attenuated seasonality due to artificial lighting, indoor
      heating during the winter and air conditioning during the summer, and promote
      sedentariness and overeating. In this setting the thrifty genes are constantly
      activated to enhance energy storage. Psychosocial stress and sleep deprivation
      are other features of modern societies. Stress-induced hypercortisolemia in the
      setting of unlimited food supply promotes adiposity. Modern man is becoming obese
      because these ancient mechanisms are efficiently promoting a positive energy
      balance. We propose that in today's plentifully provisioned societies, where
      sedentariness and mental stress have become typical traits, chronic activation of
      the neuroendocrine systems may contribute to the increased prevalence of obesity.
      We suggest that some of the yet unidentified thrifty genes may be linked to
      highly conserved energy sensing mechanisms (AMP kinase, mTOR kinase). These
      hypotheses are testable. Rural societies that are becoming rapidly industrialized
      and are witnessing a dramatic increase in obesity may provide a historical
      opportunity to conduct epidemiological studies of the thrifty genotype. In
      experimental settings, the effects of various forms of psychosocial stress in
      increasing metabolic efficiency and gene expression can be further tested.

PMID- 19156601
TI  - A comparison of cytological and parasitological methods in the diagnosis of
      Trichomonas vaginalis.
AB  - Trichomonas vaginalis (T. vaginalis), which causes urogenital system infections
      in humans, develops symptomatically and asymptomatically. T. vaginalis in females
      is diagnosed using direct microscopy, Giemsa staining, and cultivation methods
      for examination of samples derived from the vaginal posterior fornix. Serologic
      methods can also be employed. In cytological diagnosis, the ectocervical smear is
      examined using the Papanicolaou (PAPS) stain. The aim of the present study was to
      compare the efficacy of the methods used in cytological and parasitological
      diagnosis. For this purpose, 506 female patients who visited the Obstetrics and
      Gynecology policlinic of the Academic Hospital of the Faculty of Medicine, Inonu
      University during a course of six years were involved in this study. The samples
      derived from the vaginal posterior fornix were examined in the parasitology
      laboratory, while the ectocervical samples were examined in the cytology
      laboratory. T. vaginalis was detected in 4.6% of the samples examined in
      parasitology laboratory, while parasites were found in only 0.9% of the samples
      taken to the cytology laboratory. The statistical analysis revealed a significant
      difference (P<0.05). It was concluded that parasitological methods are more
      sensitive than cytological methods in the diagnosis of T. vaginalis.

PMID- 19156602
TI  - [The epidemiology of malaria in Kocaeli].
AB  - Malaria is a very important disease both for the world and Turkey. In this
      retrospective study, malaria cases detected by the Malaria Control Unit Division
      of the Bursa Health Directorship from 1997-2007 have been evaluated. During this
      ten-year period, a total of 46,959 blood specimens were examined and 64 (0.14%)
      malaria cases were detected. Out of the 64 cases of malaria, 63 (98.44%) were
      caused by Plasmodium vivax and 1 (1.56%) by Plasmodium falciparum. Of the 64
      cases, 45 (70.3%) were male and (29.7%), female. Positivity rates were found to
      be highest in 1997 and 1998. In this study, we have reviewed the malaria cases
      according to age, gender, locality and source of infection.

PMID- 19156603
TI  - [Therapeutic efficacy of buparvaquone (buparvon) in cattle with theileriosis].
AB  - The aim of this study was to examine the efficacy of buparvaquone (Buparvon,
      ALKE, Istanbul) in the treatment of theileriosis in cattle. The causative agent
      T. annulata causes direct and indirect gross economical loss in Turkey.
      Theileriosis was microscopically diagnosed by determining the presence of
      piroplasms in erythrocytes in thin blood smears stained with Giemsa stain.
      Buparvaquone was administered intramuscularly to the cattle with theileriosis
      using a single dose of 2.5 mg/kg. Clinical and laboratory examinations in cattle
      with theileriosis were carried out before and on the first, third and seventh
      days after treatment. As a result, it was concluded that a single deep
      intramuscular dose of 2.5 mg/kg buparvaquone was effective in the treatment of
      cattle which are naturally infected with T. annulata. However, further studies
      are needed using control groups of the same breed and age including suitable
      numbers of naturally infected and experimentally infected cattle.

PMID- 19156604
TI  - [Prevalence of tropical theileriosis in cattle in the Aydin Region and
      determination of efficacy of attenuated Theileria annulata vaccine].
AB  - The present study was carried out to find out the prevalence of tropical
      theileriosis in the Aydin region and to determine immune status of cattle
      vaccinated with Theileria annulata schizont vaccine using the indirect
      fluorescence antibody test (IFAT) during and after the disease season. A total of
      236 out of 466 cattle found to be seronegative with IFAT were vaccinated in the
      Aydin region (Cine, Incirliova, Nazilli, and Centrum) before the disease season
      (March). The remaining cattle (230/466) served as controls. Blood samples were
      collected from all cattle following the vaccination once in each month of April,
      June, September, and December (a total of 4 times) to determine the incidence of
      the disease using microscopic and serologic evaluations. Results indicated that
      the incidence of the disease varied among the regions. Clinical theileriosis was
      found in a total of 22 cattle (10 vaccinated, 12 unvaccinated) during the disease
      season.

PMID- 19156605
TI  - [Diagnosis of intestinal-protozoa in patients with immune deficiency].
AB  - In our study, we tried to detect gastroenteritis causing intestinal protozoa in
      patients with immune deficiency and who suffered from diarrhea. We also tried to
      determine which laboratory methods should be used in detecting intestinal
      protozoon in these patients. Thirty-six immune deficient patients who had had
      diarrhea for more than 10 days and 44 immune deficient patients without diarrhea
      were included in the study. In stool samples taken from all cases, intestinal
      protozoa were detected using the conventional diagnostic methods including direct
      wet mount, trichrome and modified acid fast staining as well as serologic
      diagnostic methods such as ELISA, direct fluorescent antibody (DFA)] and the
      molecular method of polymerized chain reaction. In our study, we found that
      intestinal protozoan such as G. intestinalis; C. parvum, B. hominis and E.
      histolytica could be responsible for the long term diarrhea in patients with
      immune deficiency. If a pathogen is not detected in the feces by native Lugol
      (NL), DFA and MAF are suitable techniques for Cryptosporidium spp while ELISA or
      trichrome staining are suitable methods for E. histolytica. It was concluded in
      the study that the simple and inexpensive NL method is sufficient in the
      diagnosis of G. intestinalis and serological or molecular methods are
      unnecessary. Neutropenia in patients with immune deficiency did not enhance the
      frequent occurrence of intestinal protozoan infections; and also, in the cases
      with immune deficiency, it was found that the administration of steroid treatment
      was not a risk factor in intestinal protozoan disease.

PMID- 19156606
TI  - [Prevalence of liver flukes in hair goats slaughtered in Hakkari (Yuksekova)
      Province].
AB  - The aim of this investigation was to determine the prevalence of distomatosis in
      267 hair goats which were slaughtered in the slaughterhouses belonging to
      butchers located in Yuksekova district of Hakkari province. In the study,
      distomatosis were detected in 165 (61.80%) of the 267 hair goats. Distomatosis
      was found in 20/98 (20.41%) hair goats which were younger than one year old and
      in 145/169 (85.80%) which were older than one year. It was found that the species
      most often responsible were Fasciola hepatica (41.21%) and Dicrocoelium
      dendriticum (42.42%). Mixed infections (F. hepatica+D. dendriticum) were found
      only in hair goats older than one year (13.94 %). In this investigation, Fasciola
      gigantica was found to infect only the ones older than one year (2.76%).

PMID- 19156607
TI  - Presence of Gasterophilus species in Arabian horses in Sanliurfa region.
AB  - In this study, ivermectin was administered orally to112 Arabian horses for
      detection of Gasterophilus species in the Sanliurfa region between June-July
      2006. Eleven (9.82%) Arabian horses were found to be infected by larvae of
      Gasterophilus spp. A total of 409 third stage larvae (L3) were collected from
      fecal samples. In the Sanliurfa region, the prevalence of three species of
      Gasterophilus was identified as follows: Gasterophilus intestinalis (6.25%), G.
      nasalis (2.67%) and G. pecorum (0.89%).

PMID- 19156608
TI  - [Problem of cystic echinococcoss in Hatay].
AB  - Echinococcosis is a zoonotic infection caused by Echinococcus granulosus and E.
      multilocularis. It continues to be a serious public health problem in many
      countries including Turkey. In Hatay, no previous study has been carried out;
      therefore, in this study, in order to determine its prevalence and to attract
      scientific attention to this issue, we have retrospectively evaluated cases of
      cystic echinococcosis in human patients presenting at the pathology laboratory of
      the Mustafa Kemal University, Faculty of Medicine, Research Hospital, as well as
      Antakya and Iskenderun State Hospitals. We have identified a total of 26 cases,
      of which 18 were in female patients (69.23%) and 8 in male patients (30.76%). The
      highest rate of cystic echinococcosis was found in the liver (57.6%), and lungs
      (19.23%). It was also found in the peritoneal region, spleen, cervical region,
      muscle, and an incision scar. In addition, the presence of cystic echinococcosis
      was investigated in 35,812 cattle slaughtered in Antakya slaughterhouse and 5,448
      (3.23%) were found to have cystic echinococcosis.

PMID- 19156609
TI  - [Demodex spp. in hairy skin biopsy specimens].
AB  - It has been reported that Demodex mites play a role in the pathogenesis of
      rosacea, acne vulgaris, perioral dermatitis, seborrhoeic dermatitis, micropapular
      pruritic dermatitis, and blepharitis. Methods used for diagnostic purposes
      included cyanoacrylic adhesives, comedone extractor, cellophane tape
      preparations, skin scraping, punch biopsy and standardized surface skin biopsy.
      This study is a retrospective work. The aim of the present retrospective study
      was the investigation of the incidence of Demodex mites using histopathological
      examination of skin biopsy specimens of keratinized cysts, fungal spores,
      tricholemmal cysts, nevi, dermatitis, fibrosis, carcinoma and inflammation of the
      scalp. Fifty-nine biopsy specimens were examined histologically after staining
      with hematoxylen-eosin. Demodex mites (i.e., tricholemmal cyst, dermatitis,
      sebaceous cyst, carcinoma, keratose cysts, nevi, fungal spores) were found in 9
      (15.3%) of them. It was concluded that since this parasite is found in
      pathological cases of the scalp, the possible role of Demodex in the pathogenesis
      of such diseases should also be evaluated.

PMID- 19156610
TI  - [The distribution of intestinal parasites and their causative factors in
      children].
AB  - Intestinal parasitic infection prevalence in children who had been brought to our
      hospital together with related factors. The study was carried out in 400 children
      who were chosen at random among those brought to our hospital. All stool samples
      were examined with nativelugol, formol-ether, Kinyon acid-fast, methods. The
      cellophane tape preparations and hemoglobin concentration measurement were used.
      Intestinal parasites found in 156 of 400 (39%) children were Giardia intestinalis
      (19.8%) Enterobius vermicularis (15%), Blastocystis hominis (5.8%). Socio
      economic and educational level of patient's family, living in urban area, having
      abdominal pain, anal itching, salivation during sleep, and nasal itching had been
      found related with the prevalence of parasitic infection. No relationship were
      found in the other factors. Because WHO guidelines favor routine screening and
      treatment of parasitic infections of school-age children when the prevalence of
      parasitic infections in community exceeds 50%, all children should be evaluated
      for parasitic infections if they have one or more risk factors.

PMID- 19156611
TI  - [Malaria control in Turkey].
AB  - Control of malaria, which is one of the best-known diseases in the human history,
      has begun to be effective in parallel to man's struggle to dominate nature.
      Occurring in the areas where agriculture is carried out, malaria has affected
      social life in the geography of Anatolia in terms of its results and attempts
      have been made to control it. Wishing to create a healthy generation free of
      disease, Turkish Republic has tried new methods with public's direct contribution
      since 1924. This struggle was successful due to with the public's submission to
      the changes in agricultural activities and life style. In contrast it was
      unsuccessful whenever the precautions were disregarded and because of this it was
      found that the outbreak of malaria reoccurred.

PMID- 19156612
TI  - [In vitro cultivation of Echinococcus granulosus].
AB  - Hydatidosis is a zoonotic disease that is caused by larva of Echinococcus
      species. It affects animals and humans and is very important from the aspect of
      health and economy. There have been many studies concerning the biology,
      physiology and biochemistry of Echinococcus granulosus which is responsible for
      hydatidosis in both humans and animals in Turkey. Frequently in vitro culture
      methods have been used in antigen production, vaccine and drug development. In
      this article, the in vitro culture of E. granulosus has been examined under
      various headings.

PMID- 19156613
TI  - [Entomophobia and delusional parasitosis].
AB  - Entomophobia is an abnormal and persistent fear of insects. Sufferers experience
      anxiety even though they realize that most insects pose no threat. A similar
      phenomenon, known as arachnophobia is fear of spiders. Delusional parasitosis
      (DP) is a hypochondrial psychosis, usually monosymptomatic, where the patient is
      convinced of being infested with animal parasites while no objective evidence
      exists to support this belief. The complaints are usually about skin infestation,
      but involvement of the gastrointestinal tract has also been described. Numerous
      samples are brought for examination from their skin, clothes and environment.
      Practically all patients refuse psychiatric help. In primary DP, the delusion
      arises spontaneously as a monodelusional disorder, while in secondary DP, the
      delusional disorder arises secondary to another major medical, neurological or
      psychiatric disorder. Shared delusion -folie a deux- is a known phenomenon in
      delusional parasitosis. One or more members of the same family often suffer from
      the same psychosis, the characteristic delusional state being identical. The
      secondary victims are often family members, who are dominated by their spouses,
      show filial devotion or are trying to keep the family in harmony. Patients whose
      delusion of parasitosis is not severe can be helped without psychopharmacological
      intervention. They can be relieved of their symptoms by giving them sympathetic
      counseling, and gaining their confidence. Symptomatic medication may be
      prescribed for the relief of pruritus, pain and other symptoms. It is more
      important to treat patients with empathy, providing a place where they can
      express their distress without being stigmatized. Second-generation
      antipsychotics such as amisulpride, risperidone or olanzapine in age-appropriate
      doses are being used today for the treatment of DP.

PMID- 19156614
TI  - Alveolar echinococcosis of liver presenting with neurological symptoms due to
      brain metastases with simultaneous lung metastasis: a case report.
AB  - Alveolar echinococcosis (AE) is a chronic and serious, even lethal, parasitic
      infection caused by the helminth Echinococcus multilocularis (EM). AE is an
      endemic disease in Turkey and it is particularly common in people living in the
      eastern Anatolia Region. In addition to various clinical presentations, symptoms
      which lead to diagnosis, however, are usually associated with the metastatic
      lesions. We herein reported a 62-year-old man who had liver alveolar hydatid
      disease with simultaneous lung and brain metastasis. We think there was only one
      therapeutic option, namely medical treatment with albendazol, which is the usual
      treatment for patients living in eastern Anatolia and who are admitted late
      resulting in a subsequent inoperable situation. Thus, radiological screening
      studies for the public in this region may increase the possibility of surgical
      treatment for alveolar hydatid disease.

PMID- 19156615
TI  - [Biliary fasciolosis: a report of three cases diagnosed by ERCP].
AB  - Fasciola hepatica is an endemic parasite in Turkey. Chronic Fasciola hepatica
      infestation is known to cause biliary obstruction and inflammation. Also, biliary
      fasciolosis may be asymptomatic. We report three patients with biliary
      fasciolosis who were diagnosed and managed by endoscopic retrograde
      cholangiopancreatography (ERCP). None of cases had eosinophilia. All cases were
      admitted to hospital with nonspecific symptoms. ERCP may be used for direct
      diagnosis and management of biliary fasciolosis.

PMID- 19156616
TI  - [A babesiosis case in February in Ankara].
AB  - Bovine babesiosis is a widespread disease occurring throughout tropical and
      subtropical regions and causes serious economical losses. Transmitted by ticks,
      Babesia species attract attention as the cause of disease and parallel the
      seasonal activity of ticks, in spring-summer months when temperatures increase.
      Ticks, that transmit the disease, belong to the Ixodidae family (pasture ticks
      hard ticks) and affect cattle that go out to pasture during the warm season. In
      this case, babesiosis was reported from a barn in Ankara, the temperatures had
      decreased to under 0 degrees C and it was snowing in February. The cattle hadn't
      been in a pasture for the past 3 months.

PMID- 19156617
TI  - A report on parasitic isopods (Crustacea) from marine fishes and decapods
      collected from a report on parasitic isopods (Crustacea) from marine fishes and
      decapods collected from the Aegean Sea (Turkey).
AB  - Parasitic isopods were investigated in marine fishes and decapods from the Aegean
      Sea during 1997-1998. A total of 10 species belonging to families Cymothoidae,
      Gnathiidae and Bopyridae was collected from various body parts of fishes and
      decapods. Ceratothoa capri and Paragnathia formica have been recorded for the
      first time from Turkish coasts.

PMID- 19156618
TI  - The morphology of Lernanthropus kroyeri van Beneden, 1851 (Copepoda:
      Lernanthropidae) parasitic on sea bass, Dicentrarchus labrax (L., 1758), from the
      Aegean Sea, Turkey.
AB  - A detailed redescription of Lernanthropus kroyeri van Beneden, 1851 is provided
      based on observations made with the aid of scanning electron microscopy.
      Specimens were obtained from the host, the sea bass Dicentrarchus labrax (L.,
      1758) obtained from a commercial aquaculture enterprise in Izmir (western
      Turkey).

PMID- 19156619
TI  - Helminth fauna of Lycisalamandra billae (Franzen & Klewen) (Luschan salamander)
      collected from Antalya.
AB  - Fifty (26 males, 21 female and 3 juvenile) Lyciasalamandra luschani (Luschan's
      salamander) collected in Antalya, were examined for helminths during 1997-2001.
      In this study, 3 helminth species, Aplectana acuminata, Cosmocerca longicauda and
      Angiostoma aspersae (Nematoda) were found. This study is the first
      helminthological research of Luschan's salamander in the world. This is the first
      time that Luschan's salamander has been shown to be the host of these parasites.

PMID- 19156620
TI  - [Helminth fauna of Hemidactylus turcicus (Linnaeus,1758) (Turkish gecko)
      collected from Hatay].
AB  - Twenty two Hemidactylus turcicus (Turkish Gecko) collected from Hatay were
      examined for helminths between 2000-2008 years. As a result of this study, 2
      helminth species (Spauligodon laevicauda and Macracanthorynchus catulinus) were
      found. This is the first time that these helminth species have been found in
      Turkey.

PMID- 19156621
TI  - The EASD/ADA consensus: trick or treat?

PMID- 19156622
TI  - Receptor for advanced glycation end-products (RAGE) and soluble RAGE (sRAGE):
      cardiovascular implications.
AB  - Disorders of glucose metabolism are associated with increased risk for
      cardiovascular disease (CVD) complications, including coronary, peripheral and
      cerebral arterial disease, that account for the majority of morbidity and
      mortality among patients with diabetes mellitus (DM). These associations between
      glucose and CVD risk extend continuously well below the glycaemic thresholds
      established for the diagnosis of diabetes, including significantly increased risk
      associated with impaired fasting glucose, impaired glucose tolerance, and even
      high normal glucose concentrations. While these epidemiological observations have
      established a clear association between cardiovascular disease and dysglycaemia
      and suggest a direct causal link, the mechanisms by which hyperglycaemia may
      contribute to the development, progression and instability of atherosclerosis
      remain unclear. A number of recent advances in the realm of vascular biology have
      identified several novel, plausible pathways that might link hyperglycaemia with
      atherosclerosis, individually or in aggregate. Key among them are the interaction
      between advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE),
      which exists as a trans-membrane signalling receptor and as a circulating form,
      soluble RAGE (sRAGE). The purpose of this review is to provide an overview of the
      present understanding of RAGE and sRAGE, their plausible role linking perturbed
      glucose metabolism with the development, progression and instability of
      atherosclerosis, and the potential therapeutic implications of modulation of this
      biological system.

PMID- 19156623
TI  - Circulating soluble CD36 is associated with glucose metabolism and interleukin-6
      in glucose-intolerant men.
AB  - Recently, soluble CD36 (sCD36) levels were reported to be elevated in type 2
      diabetes, and to be tightly correlated with insulin resistance. Our aim was to
      obtain further insight into the relationship between insulin sensitivity, low
      grade inflammation and sCD36. We studied glucose-tolerant (n=90) and glucose
      intolerant (n=57) moderately obese men. Insulin sensitivity was measured by the
      frequent sample intravenous glucose tolerance test, and sCD36 by an in-house
      ELISA assay. In glucose-intolerant subjects, sCD36 was negatively associated with
      insulin sensitivity and positively with interleukin-6 (IL-6), fasting glucose,
      fasting triglycerides, fat-free mass and platelet count. On multiple linear
      regression analyses, insulin sensitivity contributed 22% of sCD36 variance,
      independent of age, body mass index (BMI) and IL-6, in glucose-intolerant
      subjects. The level of sCD36 in subjects with glycosylated haemoglobin (HbA1C)
      above the mean was higher than in those with HbA1C values below the mean. Insulin
      sensitivity is a predictor of sCD36 in men with impaired glucose tolerance. IL-6
      is related to sCD36 but does not predict sCD36 independent of insulin sensitivity
      and BMI.

PMID- 19156624
TI  - The clinical impact of identifying metabolic syndrome in patients with diabetes:
      a cross-sectional study.
AB  - The objectives of the study were to determine whether identifying patients with
      metabolic syndrome (MetS) (as defined by International Diabetes Federation [IDF]
      criteria) among patients with diabetes would affect the decision to prescribe
      statin for primary prevention of cardiovascular disease (CVD), based on currently
      available public health guidelines. We analysed the most recent recorded CVD risk
      profiles obtained from electronic patient files from 304 general practices in
      England and Wales. Of 60,258 patients with diabetes, 11,005 men and women aged 30
      74 years fulfilled criteria for primary CVD prevention and were not on lipid
      lowering drugs. Outcome data were extrapolated to an estimated national diabetes
      prevalence of 3.6%. Identifying MetS in this group of patients would produce an
      additional 29,536 (8.4%; 95% CI: 7.7, 9.0), 104,288 (29.6%; 95% CI: 28.5, 30.7)
      and 147, 328 (41.9%; 95% CI: 40.8, 43.0) patients nationally who would not have
      been eligible otherwise for primary CVD prevention strategies with statins, based
      on the Joint British Societies', the National Institute for Health and Clinical
      Excellence and the General Medical Services contract guidelines, respectively.
      The sensitivity and positive predictive value of these different strategies to
      detect metabolic syndrome were 87.5% and 69.1%; 57.3% and 76.8%; and 37.8% and
      70.2%, respectively. In conclusion, among individuals with diabetes, identifying
      patients with MetS may further increase the use of statin therapy for primary CVD
      prevention.

PMID- 19156625
TI  - Long-term hyperglycaemia impairs vascular smooth muscle cell function in women
      with type 1 diabetes mellitus.
AB  - Observations of increased stiffness in the elastic aorta in women with diabetes,
      but not men, emphasise the need for further analysis regarding early
      abnormalities in arterial wall properties of women with type 1 diabetes mellitus
      (DM). Ultrasound was used to study the wall properties of the distal brachial
      artery (BA) in 37 type 1 diabetic women (aged 22-45 years) without evident
      complications and in 53 controls (C). Blood samples were drawn for later
      analysis. Flow-mediated dilatation (FMD) was slightly lower in DM than C, 8.1+/
      4.3% vs. 10.3+/-4.9% (p<0.05), and nitrate-mediated dilatation (NMD) was markedly
      lower, 21.7+/-6.6% vs. 31.4+/-5.7% (p<0.001). Lumen diameter, intima-media
      thickness and distensibility were similar in DM and C. Insulin-like growth factor
      (IGF-1) was lower in DM than C, 231+/-65 vs. 349+/-68 ng/ml (p<0.001).
      Glycosylated haemoglobin (HbA1C) and matrix metalloproteinase (MMP-9) were
      independent predictors of the reduced NMD in the DM. Brachial artery
      responsiveness to an exogenous donor of nitric oxide (NO) was markedly reduced in
      type 1 diabetic women despite only limited reduction in endothelium-dependent
      dilatation. The negative association between NMD and HbA1C suggests that long
      term hyperglycaemia impairs vascular smooth muscle cell function in DM.

PMID- 19156626
TI  - Metabolic syndrome and its single traits as risk factors for diabetes in people
      with impaired glucose tolerance: the STOP-NIDDM trial.
AB  - The STOP-NIDDM trial was an international, double-blind, placebo-controlled
      randomised study in people with impaired glucose tolerance (IGT). They were
      treated with an alpha-glucosidase inhibitor, acarbose, to prevent diabetes; the
      overall number needed to treat (NNT) was 11. In a secondary analysis, we
      considered the impact of single traits and overall metabolic syndrome (MetS)
      respectively on risk of diabetes and NNT respectively. In all, there were 1,368
      patients. They were followed up for 3.3 years, and the prevalence of MetS was
      61%. Multivariate analysis revealed treatment group 2-hour (post-challenge)
      plasma glucose, glycosylated haemoglobin (HbA1C), triglycerides and leukocyte
      count as independent predictors. The annual incidence of diabetes in the placebo
      group with MetS was 18.7% vs. 11.2% in patients without MetS; the corresponding
      figures in the acarbose group were 13.5% and 9.4%, respectively. The NNT in
      patients was 5.8 in patients with MetS and 16.5 in those without MetS. In
      conclusion, most single traits and overall MetS label a very high-risk group in
      people with IGT. People with MetS reach a NNT to prevent development of new
      diabetes with acarbose of 5.8.

PMID- 19156627
TI  - Evaluation of sexual function in women with type 2 diabetes mellitus.
AB  - Sexual health is an important, but often neglected, component of diabetes care.
      In contrast to erectile dysfunction among men with diabetes, female sexual
      dysfunction has not been well studied among diabetic women. The aim of this study
      was to assess the prevalence of sexual dysfunction in women with type 2 diabetes
      compared to that in an age-matched control group. In all, 50 married women with
      type 2 diabetes attending the outpatient endocrine clinic of Ghaem Hospital
      between April 2007 and March 2008 were selected. Fasting plasma glucose and
      glycosylated haemoglobin were measured and sexual function was assessed by
      questionnaire. Scores in each domain of sexual function were compared with those
      of 40 non-diabetic controls. Sexual function scores for the sexual drive,
      arousal, vaginal lubrication, orgasm and overall satisfaction domains were all
      lower in the diabetic women (p value < 0.05). Duration of diabetes and age
      correlated negatively with all domains of sexual function. There was no
      significant relationship between sexual function and body mass index (BMI),
      glycaemic control, education or employment status. Diabetes significantly impairs
      the sexual performance of diabetic women. Determinants of sexual function include
      age and duration of diabetes.

PMID- 19156628
TI  - Is nuclear magnetic resonance lipoprotein subclass related to diabetic
      retinopathy? The multi-ethnic study of atherosclerosis (MESA).
AB  - OBJECTIVE: To examine the associations between nuclear magnetic resonance (NMR)
      defined lipoproteins and diabetic retinopathy (DR) in a population-based sample
      of adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: In all, 921 persons
      with diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA) were included.
      DR was assessed from retinal photographs. Lipoproteins were measured by NMR
      spectroscopy. RESULTS: After controlling for age, race/ethnicity, study centre
      and diabetes and vascular risk factors, no consistent patterns of associations
      between NMR-defined lipoprotein particle concentrations and subclass with DR were
      evident. CONCLUSION: The lack of association between NMR-defined lipoproteins and
      DR does not support clinical use of NMR spectroscopy for management of patients
      with DR.

PMID- 19156629
TI  - The effect of rosiglitazone on integrated cardiovascular performance, cardiac
      structure, function and myocardial triglyceride: trial design and rationale.
AB  - The thiazolidinedione (TZD) class of medications has been associated with
      increased risk for peripheral oedema, as well as incident and worsening heart
      failure (HF). The mechanism of these observed effects remains unclear. Here we
      present the rationale and study design for a randomised clinical trial designed
      to evaluate the cardiac effects of rosiglitazone on integrated cardiovascular
      performance, cardiac structure and function. The study is a randomised, single
      centre, double-blind, placebo-controlled, parallel-group clinical trial to
      evaluate the effect of rosiglitazone on integrated cardiovascular performance in
      a cohort of patients with type 2 diabetes mellitus (T2DM) at increased risk for
      developing heart failure (HF). Participants will be randomised to receive
      rosiglitazone or matching placebo for six months. All subjects will undergo
      maximal treadmill cardiopulmonary exercise testing at baseline and after six
      months on study drug, with the primary trial end point of peak oxygen uptake
      indexed to fat-free mass (VO 2peak-FFM). Approximately two-thirds of the study
      cohort will undergo cardiac magnetic resonance imaging (MRI) and spectroscopy
      (MRS) at baseline and after six months of study therapy to assess cardiac
      structure, function and myocardial triglyceride content. While concerns for
      peripheral oedema and HF continue to confound clinical use of TZD medications,
      the direct cardiac effects of these drugs remain poorly understood and the
      clinical relevance of these clinical observations remains unclear. The present
      study will combine a series of state-of-the-art assessments to evaluate the
      cardiac effects of rosiglitazone treatment.

PMID- 19156632
TI  - The 10-year post-trial follow-up of the United Kingdom Prospective Diabetes Study
      (UKPDS): cardiovascular observations in context.

PMID- 19156630
TI  - Rosiglitazone increases testosterone in hypogonadal type 2 diabetic men.

PMID- 19156633
TI  - Use of fullerene-, octadecyl-, and triaconthyl silica for solid phase extraction
      of tryptic peptides obtained from unmodified and in vitro glycated human serum
      albumin and fibrinogen.
AB  - SPE plays a crucial role in bioanalytical research. In the present work a novel
      fullerene(C60)-derivatised silica material is compared with octadecyl(C18) - and
      triaconthyl(C30)-silicas regarding recoveries of peptides and sequence coverage
      of HSA and fibrinogen digests. C30- and C60(30 nm)-SPE materials were found to be
      the two most prominent SPE materials. At low peptide concentrations C60-material
      prepared from a silica gel with a pore size of 30 nm has proven to be the best
      material with regards to recoveries. By increasing the amount of loaded peptides
      recoveries decrease due to its relative low binding capacity in contrast to C30
      silica particles, showing no changes. The best sequence coverages of Aalpha- and
      Bbeta-chains of 20 pmol fibrinogen digest can also be achieved using these two
      SPE materials, C60 (30 nm) demonstrates an outstanding value of sequence coverage
      (62.15%) achieved for the gamma-chain. After nonenzymatic glycation the digests
      of fibrinogen and HSA were also separated. This makes the detection of a
      considerably higher number of glycated peptides possible compared to the
      unfractionated digests and the use of boronate affinity chromatography in the
      case of fibrinogen. For HSA, ten new sites of glycation at lysine and arginine
      residues have been explored. Using the detailed SPE/off-line MALDI method the
      glycation sites on fibrinogen are first described in this paper.

PMID- 19156640
TI  - The emerging technique, microextraction in packed syringes in separation science-
      can it eliminate matrix effects and fit with LC/MS/MS strategy?

PMID- 19156634
TI  - Enrichment of the thymoquinone content in volatile oil from Satureja montana
      using supercritical fluid extraction.
AB  - Supercritical fluid extraction (SFE) of the volatile oil from Satureja montana L.
      was performed under different conditions of pressure (90 and 100 bar),
      temperature (40 and 50 degrees C), mean particle sizes (0.4, 0.6 and 0.8 mm) and
      CO(2) flow rate (0.8, 1.1 and 1.3 kg/h) to understand the influence of these
      parameters on the composition and yield of this oil. The results were compared
      with those obtained for the essential oil isolated by hydrodistillation (HD). The
      volatile and the essential oil were analysed by GC and GC-MS. The main compounds
      are carvacrol (52.2-62.0% for HD vs. 41.7-64.5% for SFE), thymol (8.6-11.0% for
      HD vs. 6.0-11.3% for SFE), p-cymene (6.9-12.8% for HD vs. 6.0-17.8% for SFE),
      gamma-terpinene (6.4-9.4% for HD vs. 2.3-6.0% for SFE) and beta-bisabolene (2.0
      2.7% for HD vs. 2.2-3.5% for SFE). The major difference between SFE and HD was
      the relative amount of thymoquinone, an oxygenated monoterpene with important
      biological activities, which can be ten-fold higher in volatile oil (1.6-3.0 for
      SFE vs. 0.2% for HD). The morphology of the glandular trichomes of S. montana and
      the effect of the grinding process on them was also evaluated by SEM.

PMID- 19156641
TI  - Unique potentiometric detection systems for HPLC determination of some steroids
      in human urine.
AB  - Isocratic HPLC with potentiometric detection is used for the determination of
      some 17-ketosteroids (17-KS), e.g., androsterone, dehydroepiandrosterone and
      estrone, and their respective sulfated conjugates (17-KSS). Glassy carbon or
      composite electrodes containing a mixture of graphite and poly(vinyl chloride),
      PVC, were used as substrate electrodes. These substrates were covered either by
      montmorillonite or potassium tetrakis(p-chlorophenyl) borate containing PVC-based
      rubber phase membranes. The neutral 17-KS compounds were derivatized with
      Girard's reagent P (GP) to obtain cationic pyridinium acetohydrazones prior to
      the HPLC/potentiometric detection assay. No side reactions were observed, and the
      GP itself was not interfering. The method yielded accurate and reproducible
      results and was applicable to samples containing down to micromolar
      concentrations. Next, the 17-KSS compounds, acting as anionic charged molecules,
      were determined directly in human urine samples with the HPLC/potentiometry
      combination without preliminary derivatization. For this purpose, a new anion
      sensitive potentiometric electrode was developed using a macrocyclic polyamine
      containing, PVC-based, rubber phase membrane. The three 17-KSS compounds were
      also determined accurately down to micromolar concentrations. Especially, the
      main androgen metabolites as dehydroepiandrosterone sulfate and androsterone
      sulfate could be selectively determined with a developed potentiometric sensor in
      human urine samples without time-consuming cleanup and preconcentration step.

PMID- 19156642
TI  - Preparative purification of salidroside from Rhodiola rosea by two-step
      adsorption chromatography on resins.
AB  - Salidroside is an effective adaptogenic drug extracted from Rhodiola species. In
      the present study, a simple and efficient method for preparative separation and
      purification of salidroside from the Chinese medicinal plant Rhodiola rosesa was
      developed by adsorption chromatography on macroporous resins. The static
      adsorption isotherms and kinetics of some resins have been determined and
      compared for preparative separation of salidroside. According to our results, HPD
      200 resin is the most appropriate medium for the separation of salidroside and
      its adsorption data fit the Langmuir isotherm well. Dynamic adsorption and
      desorption were carried out in glass columns packed with HPD-200 to optimize the
      separation process. After two adsorption and desorption runs, a product with a
      salidroside content of 92.21% and an overall recovery of 48.82% was achieved. In
      addition, pure lamellar crystals of salidroside with a purity of 99.00% could be
      obtained from this product. Its molecular weight was determined by an ESI-MS
      method. The simple purification scheme avoids toxic organic solvents used in
      silica gel and high-speed counter-current chromatographic separation processes
      and thus increases the safety of the process and can be helpful for large-scale
      salidroside production from Rhodiola rosea or other plant extracts.

PMID- 19156644
TI  - Method to predict the bandwidth of elution profile under the linear gradient
      elution in reversed-phase HPLC.
AB  - Solute migration in a chromatographic column is an important consideration when
      designing batch or continuous chromatographic separation processes. Most design
      methods for the chromatographic processes are based on the equilibrium theory
      which concerns only the migration velocity of the solute. However, in real cases,
      it is important to predict the zone spreading which occurs by axial dispersion
      and mass transfer resistance. To predict the actual solute profiles in the column
      or effluent stream, numerical methods to solve nonlinear partial differential
      equations have been used. However, these methods involve much time and expense.
      In this work, two different rate factors are considered to predict the
      characteristics of the solute profiles. The first is solute migration velocity
      and the second is the zone spreading rate. The zone spreading rate can be
      estimated by the apparent axial dispersion coefficient which is obtained from the
      height of the equivalent theoretical plate in particular. Four benzene
      derivatives (benzene, toluene, p-xylene, and acetophenone) were used as model
      solutes, and two mobile phase systems, water/methanol and water/ACN, were used in
      RP-HPLC. The bandwidths and retention times of the solutes were predicted under
      several linear gradient conditions. The predicted and experimental bandwidths and
      retention times showed good agreement.

PMID- 19156643
TI  - Rapid simultaneous determination of codeine and morphine in plasma using LC-ESI
      MS/MS: application to a clinical pharmacokinetic study.
AB  - A rapid and sensitive high-performance LC-MS/MS method was developed and
      validated for the simultaneous quantification of codeine and its metabolite
      morphine in human plasma using donepezil as an internal standard (IS). Following
      a single liquid-liquid extraction with ethyl acetate, the analytes were separated
      using an isocratic mobile phase on a C(18 )column and analyzed by MS/MS in the
      selected reaction monitoring mode using the respective [M+H](+ )ions, mass-to
      charge ratio (m/z) 300/165 for codeine, m/z 286/165 for morphine and m/z 380/91
      for IS. The method exhibited a linear dynamic range of 0.2-100/0.5-250 ng/mL for
      codeine/morphine in human plasma, respectively. The lower LOQs were 0.2 and 0.5
      ng/mL for codeine and its metabolite morphine using 0.5 mL of human plasma.
      Acceptable precision and accuracy were obtained for concentrations over the
      standard curve range. A run time of 2.0 min for each sample made it possible to
      analyze more than 300 human plasma samples per day. The validated LC-MS/MS method
      was applied to a pharmacokinetic study in which healthy Chinese volunteers each
      received a single oral dose of 30 mg codeine phosphate.

PMID- 19156645
TI  - Comparative analysis of volatile constituents between recipe jingfangsan and its
      single herbs by GC-MS combined with alternative moving window factor analysis
      method.
AB  - Comparative analysis of volatile constituents between recipe jingfangsan and its
      single herbs was performed by GC-MS combined with alternative moving window
      factor analysis (AMWFA), a new chemometric resolution method. Identification of
      the compounds was also assisted by comparison of temperature-programmed retention
      indices (PTRIs) on the OV-1 column with authentic samples. In total, 36, 29, and
      42 volatile components in essential oil of Herba schizonepetae (HS), Radix
      saposhnikoviae (RS), and the recipe were respectively determined qualitatively
      and quantitatively, accounting for 81.80, 82.62 and 85.98% total contents of
      volatile oil of HS, RS, and the recipe respectively. Analysis by the method of
      AMWFA indicates that there are 22 common volatile constituents between the recipe
      and single herbal medicine HS, and 14 common volatile constituents between the
      recipe and single herb medicine RS. The experimental results also show that the
      volatile components of the recipe in number are almost addition of that of two
      single herbal medicines HS and RS, and are mainly from the single herbal medicine
      HS.

PMID- 19156646
TI  - Determination of D,L-serine in midbrain of Parkinson's disease mouse by capillary
      electrophoresis with in-column light-emitting diode induced fluorescence
      detection.
AB  - A capillary electrophoresis method with in-column light-emitting diode induced
      fluorescence detection is described for simultaneous determination of D,L-serine
      in the midbrain of a Parkinson's disease mouse. D,L-Serine was derivatized with
      fluorescein isothiocyanate, and chiral separation and determination of D,L-serine
      derivatives were performed on a laboratory-built capillary electrophoresis system
      with in-column light-emitting diode induced fluorescence detector using gamma
      cyclodextrin as chiral selector. Using this method, the levels of D- and L-serine
      in the midbrains of Parkinson's disease mice were determined. When compared to
      controls, the levels of D- and L-serine showed significant differences. The
      result suggested that the biosynthesis and the transportation of endogenous D,L
      serine may participate in Parkinson's disease pathogenesis.

PMID- 19156647
TI  - Binder phenotype: clinical and etiological heterogeneity of the so-called Binder
      maxillonasal dysplasia in prenatally diagnosed cases, and review of the
      literature.
AB  - OBJECTIVE: Prenatal Binder profile is a well known clinical phenotype, defined by
      a flat profile without nasal eminence, contrasting with nasal bones of normal
      length. Binder profile results of a hypoplasia of the nasal pyramid (sometimes
      referred to as maxillonasal dysplasia). We report 8 fetuses prenatally diagnosed
      as Binder phenotype, and discuss their postnatal diagnoses. METHODS:
      Ultrasonographic detailed measurements in 2D and 3D were done on the 8 fetuses
      with Binder profile, and were compared with postnatal phenotype. RESULTS: All
      fetuses have an association of verticalized nasal bones, abnormal convexity of
      the maxilla, and some degree of chondrodysplasia punctata. The final diagnoses
      included fetal warfarin syndrome (one patient), infantile sialic acid storage
      (one patient), probable Keutel syndrome (one patient), and five unclassifiable
      types of chondrodysplasia punctata. CONCLUSION: This series demonstrates the
      heterogeneity of prenatally diagnosed Binder phenotype, and the presence of
      chondrodysplasia punctata in all cases. An anomaly of vitamin K metabolism,
      possibly due to environmental factors, is suspected in these mild
      chondrodysplasia punctata. We recommend considering early prophylactic vitamin K
      supplementation in every suspected acquired vitamin K deficiency including
      incoercible vomiting of the pregnancy.

PMID- 19156648
TI  - Alpha- and beta-glycosyl sulfonium ions: generation and reactivity.
AB  - Low-temperature electrochemical oxidation of thioglycosides gave glycosyl
      triflates from which glycosyl sulfonium ions were produced (see scheme). The
      latter were characterized by NMR spectroscopy and cold-spray mass spectrometry as
      a mixture of alpha- and beta-isomers (45:55). The alpha-glycosyl sulfonium ion
      exhibited higher reactivity than the beta-glycosyl sulfonium ion in the reaction
      with methanol, which gave a mixture of alpha- and beta-methyl glycosides (41:59).

PMID- 19156649
TI  - Understanding the plasticity of the alpha/beta hydrolase fold: lid swapping on
      the Candida antarctica lipase B results in chimeras with interesting biocatalytic
      properties.
AB  - The best of both worlds. Long molecular dynamics (MD) simulations of Candida
      antarctica lipase B (CALB) confirmed the function of helix alpha5 as a lid
      structure. Replacement of the helix with corresponding lid regions from CALB
      homologues from Neurospora crassa and Gibberella zeae resulted in new CALB
      chimeras with novel biocatalytic properties. The figure shows a snapshot from the
      MD simulation. The Candida antarctica lipase B (CALB) has found very extensive
      use in biocatalysis reactions. Long molecular dynamics simulations of CALB in
      explicit aqueous solvent confirmed the high mobility of the regions lining the
      channel that leads into the active site, in particular, of helices alpha5 and
      alpha10. The simulation also confirmed the function of helix alpha5 as a lid of
      the lipase. Replacing it with corresponding lid regions from the CALB homologues
      from Neurospora crassa and Gibberella zeae resulted in two new CALB mutants.
      Characterization of these revealed several interesting properties, including
      increased hydrolytic activity on simple esters, specifically substrates with
      C(alpha) branching on the carboxylic side, and much increased enantioselectivity
      in hydrolysis of racemic ethyl 2-phenylpropanoate (E>50), which is a common
      structure of the profen drug family.

PMID- 19156650
TI  - A theoretical study on the electronic states and O-loss photodissociation of the
      NO2(+) ion.
AB  - CASPT2 (multiconfiguration second-order perturbation theory) calculations were
      performed at the molecular geometry for 17 low-lying singlet and triplet states
      of the NO(2)(+) ion. The CASPT2 vertical relative energies (T(v)') were obtained
      and the characters of these ionic states (primary or shake-up ionization states)
      were determined. For the eight low-lying states, we performed CASPT2 geometry
      optimization calculations and obtained the CASPT2 adiabatic relative energies
      (T(0)). We conclude that the 1(1)A(1), 1(3)B(2), 1(3)A(2), 1(1)A(2), 1(1)B(2),
      1(3)A(1), 2(3)B(1), and 3(3)B(2) states of NO(2)(+) correspond to the
      X(1)Sigma(g)(+), a(3)B(2), b(3)A(2), A(1)A(2), B(1)B(2), c(3)A(1), d(3)B(1), and
      (3b(2))(-1) (3)B(2) states (the eight ionic states below 20 eV observed in the
      photoelectron spectra of Brundle et al.1 and Baltzer et al.2), respectively. The
      1(1)A(1), 1(3)B(2), 1(3)A(2), 1(1)A(2), 1(1)B(2), 1(3)A(1), and 3(3)B(2) states
      are primary ionization states, and the CASPT2 T(v)' and T(0) values of these
      states are close to the corresponding experimental values from refs. [1] and [2].
      The 2(3)B(1) state is not a typical primary ionization state, and the CASPT2
      T(v)' and T(0) values for 2(3)B(1) are in reasonable agreement with the
      experimental values for d(3)B(1) from refs. [1] and [2] (the CASPT2 T(0) value
      for 1(3)B(1) is more than 2.5 eV smaller than the experimental values). Based on
      our CASPT2 T(0) calculations, we comment on the assignments of the d(3)A(1),
      C(1)B(1), and D(1)B(2) states below 20 eV observed by Jarvis et al. and on the
      MRCI T(0) values of Hirst for the 1(3)B(1), 1(1)B(1), and (3)A(1) states. On the
      basis of the CASPT2 potential energy curve (PEC) and CASSCF singlet/triplet
      minimum-energy crossing point (MECP) calculations, we reach the following
      conclusions concerning O-loss photodissociation from the X(1)Sigma(g)(+),
      a(3)B(2), b(3)A(2), A(1)A(2), and B(1)B(2) states, which are in line with the
      experimental facts. The adiabatic dissociation process of the X(1)Sigma(g) (+)
      state to the second limit [NO(+)(X(1)Sigma(+))+O((1)D)] cannot occur due to a
      high energy barrier (>5.0 eV) along the PEC, and the nonadiabitic process of
      X(1)Sigma(g)(+) to the first limit [NO(+)(X(1)Sigma(+))+O((3)P)] via the triplet
      states is unlikely since the MECPs lie very high above X(1)Sigma(g)(+). For the
      a(3)B(2) and b(3)A(2) states, adiabatic dissociation processes to the first limit
      may occur. Both the A(1)A(2) and B(1)B(2) states can undergo processes of
      predissociation to the first limit by a repulsive 2(3)A'' state, since the MECPs
      lie low above A(1)A(2) and B(1)B(2) and the calculated spin-orbit couplings at
      the MECPs are not small.

PMID- 19156651
TI  - Efficient synthesis of highly active phospha-isosteres of the influenza
      neuraminidase inhibitor oseltamivir.
AB  - With a Hunsdiecker-Barton iododecarboxylation strategy, we converted the
      carboxylate group of the oseltamivir precursor into exemplary phosphonate
      monoesters. In all cases, K(i) values towards influenza virus sialidase remained
      in the sub-nanomolar range. We have thus made valuable structural space available
      for the design of novel oseltamivir-based tools for influenza virus research.

PMID- 19156652
TI  - Bridging the materials gap in catalysis: entrapment of molecular catalysts in
      functional supports and beyond.
AB  - Rising sun of the materials world: Tremendous efforts are being made to combine
      the potential of molecular catalysts with that of functional supports. An
      approach towards unifying homogeneous and heterogeneous catalysis is the
      entrapment of organometallic catalysts in a metal matrix, which leads to well
      defined composites that are suitable as heterogeneous catalysts for hydrogenation
      of styrene and diphenylacetylene.

PMID- 19156653
TI  - Organocatalytic asymmetric alkylation of aldehydes by S(N)1-type reaction of
      alcohols.
AB  - Work-alcoholic! The elusive enantioselective catalytic alpha-alkylation of
      aldehydes, a widely sought transformation, was brought to execution by the use of
      alcohols capable of forming stabilized carbocations (see scheme, TFA =
      trifluoroacetic acid).

PMID- 19156654
TI  - A palladium(II)-catalyzed synthesis of spiroacetals through a one-pot
      multicomponent cascade reaction.
AB  - Functionalized spiroacetals have been easily prepared in a one-pot three
      component coupling process that involves the reaction of pentynol derivatives,
      salicylaldehydes, and amines in the presence of catalytic amounts of a
      palladium(II) complex (see scheme). Alternatively, oxygen-substituted
      spiroacetals can be obtained by using orthoesters as the third component.

PMID- 19156655
TI  - Synthesis of a sialic acid containing complex-type N-glycan on a solid support.
AB  - A new solid-phase synthesis of N-linked glycans featuring 1) highly
      stereoselective beta-mannosylation and microfluidic alpha-sialylation and 2)
      efficient glycosylation of the N-phenyltrifluoroacetimidate units on JandaJel
      resin is reported. Reagent concentration effects by a fluorous solvent are
      effectively applied, and the use of these methods results in the first synthesis
      of a sialic acid containing complex-type N-glycan on a solid support.

PMID- 19156656
TI  - Synthesis, characterization, cytotoxicity, and hydrolytic behavior of C2- and C1
      symmetrical Ti(IV) complexes of tetradentate diamine bis(phenolato) ligands: a
      new class of antitumor agents.
AB  - We recently introduced a new class of bis(isopropoxo)-Ti(IV) complexes with
      diamine bis(phenolato) ligands that possess antitumor activity against colon HT
      29 and ovarian OVCAR-1 cells that is higher than that of the known Ti(IV)
      compounds titanocene dichloride and budotitane as well as that of cisplatin.
      Herein, we elaborate on this family of compounds; we discuss the effect of
      structural parameters on the cytotoxic activity and hydrolytic behavior of these
      complexes, seeking a relationship between the two. Whereas complexes with small
      steric groups around the metal center possess high activity and lead mostly to
      formation of O-bridged polynuclear complexes with bound bis(phenolato) ligand
      upon water addition, bulky complexes hydrolyze to release all free ligands and
      are inactive. Slightly increasing the size of the N-donor substituents probably
      weakens the ligand binding in solution, and, thus, rapid hydrolysis is observed,
      leading to a lack of cytotoxicity, supporting the requirement for ligand
      inertness. Replacing the two isopropoxo ligands with a single catecholato unit
      gives a complex with a different geometry that exhibits slower hydrolysis and
      reduced cytotoxicity, suggesting some participation of labile ligand hydrolysis
      in the cytotoxicity mechanism. A crystallographically characterized O-bridged
      polynuclear species obtained from a biologically active bis(isopropoxo) complex
      upon water addition is inactive, which rules out its participation as the active
      species, yet suggests some role of the particular steric and electronic
      requirements allowing its formation in the activity mechanism. Additional
      measurements support rapid formation of the active species in the presence of
      cells prior to O-bridged Ti(IV) cluster formation.

PMID- 19156657
TI  - Distinct hydroxy-radical-induced damage of 3'-uridine monophosphate in RNA: a
      theoretical study.
AB  - RNA strand scission and base release in 3'-uridine monophosphate (UMP), induced
      by OH radical addition to uracil, is studied at the DFT B3LYP/6-31+G(d,p) level
      in the gas phase and in solution. In particular, the mechanism of hydrogen-atom
      transfer subsequent to radical formation, from C2' on the sugar to the C6 site on
      the base, is explored. The barriers of (C2'-)H2'(a) abstraction by the C6 radical
      site range from 11.2 to 20.0 kcal mol(-1) in the gas phase and 14.1 to 21.0 kcal
      mol(-1) in aqueous solution, indicating that the local surrounding governs the
      hydrogen-abstraction reaction in a stereoselective way. The calculated N1-C1' (N1
      glycosidic bond) and beta-phosphate bond strengths show that homolytic and
      heterolytic bond-breaking processes are largely favored in each case,
      respectively. The barrier for beta-phosphate bond rupture is approximately 3.2
      4.0 kcal mol(-1) and is preferred by 8-12 kcal mol(-1) over N1-glycosidic bond
      cleavage in both the gas phase and solution. The beta-phosphate bond-rupture
      reactions are exothermal in the gas phase and solution, whereas N1-C1' bond
      rupture reactions require both solvation and thermal corrections at 298 K to be
      energetically favored. The presence of the ribose 2'-OH group and its formation
      of low-barrier hydrogen bonds with oxygen atoms of the 3'-phosphate linkage are
      highly important for hydrogen transfer and the subsequent bond-breakage
      reactions.

PMID- 19156658
TI  - Influence of the charge state on the structures and interactions of vancomycin
      antibiotics with cell-wall analogue peptides: experimental and theoretical
      studies.
AB  - Charge matters! The charge state significantly influences the conformation and
      the binding energy between vancomycin antibiotic and bacterial cell-wall analogue
      peptides (see figure). Surface-induced dissociation (SID) studies provide a
      quantitative comparison between the stabilities of different charge states of the
      complex.In this study we examined the effect of the charge state on the
      energetics and dynamics of dissociation of the noncovalent complex between the
      vancomycin and the cell-wall peptide analogue N(alpha),N(epsilon)-diacetyl-L-Lys
      D-Ala-D-Ala (V-Ac(2)LKdAdA). The binding energies between the vancomycin and the
      peptide were obtained from the RRKM (Rice, Ramsperger, Kassel, Marcus) modeling
      of the time- and energy-resolved surface-induced dissociation (SID) experiments.
      Our results demonstrate that the stability of the complex towards fragmentation
      increases in the order: doubly protonated<singly protonated<deprotonated.
      Dissociation of the singly protonated and singly deprotonated complex is
      characterized by very large entropy effects, which indicate a substantial
      increase in the conformational flexibility of the resulting products. The
      experimental threshold energies of (1.75+/-0.08) eV ((40.3+/-1.8) kcal mol(-1))
      and (1.34+/-0.08) eV ((30.9+/-1.8) kcal mol(-1)) obtained for the deprotonated
      and singly protonated complexes, respectively, are in excellent agreement with
      the results of density functional theory calculations. The increased stability of
      the deprotonated complex observed experimentally is attributed to the presence of
      three charged sites in the deprotonated complex, as compared with only one
      charged site in the singly protonated complex. The low binding energy of (0.93+/
      0.04) eV ((21.4+/-0.9) kcal mol(-1)) obtained for the doubly protonated complex
      suggests that this ion is destabilized by Coulomb repulsion between the singly
      protonated vancomycin and the singly protonated peptide comprising the complex.

PMID- 19156659
TI  - Recent developments in capillary EKC based on carbon nanoparticles.
AB  - This paper provides an overview of the use of carbon nanoparticles (CNPs) as
      pseudo-stationary phases (PSPs) in EKC. Specifically, it describes the
      characteristics and properties of the major types of CNPs used as PSPs in EKC
      separations, namely C(60) fullerenes, carbon nanotubes and covalently modified
      carbon nanotubes. Based on such properties, a plausible mechanism for the
      interactions governing EKC separation with these materials is proposed. Also, the
      most salient uses of CNPs as PSPs are outlined. Finally, CNPs are compared in
      terms of performance with other well-established types of nanostructures used to
      enhance selectivity in EKC over the past decade.

PMID- 19156660
TI  - Electrolyte systems for on-line CE-MS: detection requirements and separation
      possibilities.
AB  - In contemporary analytical practice, the on-line CE-MS technique has established
      as a powerful separation and identification analytical tool. Its major
      instrumental aspects can be considered as solved and its routine use with
      specific applications to be implemented is the typical task at present. In that
      context, the chemical (wet, electrophoretic) part of the technique becomes very
      important as here the separation battle of the overall success of the developed
      method is fought. The review brings an overview of the electrolyte systems used
      in the CE part of the CE-MS technique together with a detailed insight into their
      pros and cons from the electrophoretist's viewpoint. Advanced electrophoretic
      approaches including sample stacking, ITP and use of non-aqueous solvents are
      also discussed. An overview of the electrolyte systems used in over 200 selected
      applications is given, sorted according to the analytes of interest.

PMID- 19156661
TI  - Recent advances in enhancing the sensitivity of electrophoresis and
      electrochromatography in capillaries and microchips (2006-2008).
AB  - Poor sensitivity is still considered to be one of the major limitations of
      electrophoresis, which is surprising given the power, flexibility and versatility
      of many of the approaches to on-line concentration that have developed over the
      last 20 years. This is still a very active area of interest and this review will
      cover developments in the field over the last two years since the last review
      (Electrophoresis 2007, 28, 254-281) through to June 2008. It includes
      developments in the fields of stacking, covering all methods from field-amplified
      sample stacking and large volume sample stacking, through to ITP, dynamic pH
      junction and sweeping. Attention is also given to on-line or in-line extraction
      methods that have been used for electrophoresis.

PMID- 19156662
TI  - Recent advances in capillary and microfluidic platforms with MS detection for the
      analysis of phosphoproteins.
AB  - Reversible protein phosphorylation represents a key regulatory mechanism that
      triggers essential cellular signaling events. The large-scale characterization of
      protein phosphorylation in a cell represents, therefore, the objective of many
      biological studies that aim at elucidating the complex signaling pathways that
      are involved in the progression and/or regression of a disease. The recent
      implementation of novel MS detection strategies has significantly advanced the
      capabilities for interrogating the complex cellular phosphoproteome.
      Simultaneously, the current advent of miniaturized technologies has clearly
      demonstrated the superior performance of microfluidic instrumentation for
      bioanalytical and biological applications that cope with speed, sensitivity and
      throughput-related demands. This review aims at providing an update on the latest
      developments regarding the interfacing of microfluidic devices with MS detection
      for exploring the challenging area of phosphoproteomics.

PMID- 19156665
TI  - The combination of flow injection with electrophoresis using capillaries and
      chips.
AB  - The technique of combined flow injection CE (FI-CE) integrates the essential
      favorable merits of FI and CE. It utilizes the various excellent on-line sample
      pretreatments and preconcentration (such as cloud point extraction, SPE, ion
      exchange, dynamic pH junction and head-column field-amplified sample stacking
      technique) of FI, which has the advantages of high speed, accuracy, precision and
      avoiding manual handling of sample and reagents. Therefore, the coupling of FI-CE
      is an attractive technique; it can significantly expand the application of CE and
      has achieved many publications since its first appearance. The basic principles,
      instrumental developments and applications of FI-CE system from 2006 to 2008 are
      reviewed.

PMID- 19156666
TI  - CE and CEC Reviews. Editorial.

PMID- 19156667
TI  - The importance of signal pathway modulation in all aspects of tooth development.
AB  - Most characteristics of tooth shape and pattern can be altered by modulating the
      signal pathways mediating epithelial-mesenchymal interactions in developing
      teeth. These regulatory signals function in complex networks, characterized by an
      abundance of activators or inhibitors. In addition, multiple specific inhibitors
      of all conserved signal pathways have been identified as modulators in tooth
      development. The number of teeth as well as molar cusp patterns can be modified
      by tinkering with several different signal pathways. The inhibition of any of the
      major conserved signal pathways in knockout mice leads to arrested tooth
      formation. On the other hand, the stimulation of the Wnt pathway in the oral
      epithelium in transgenic mice leads to abundant de novo tooth formation. The
      modulation of some of the signal pathways can rescue the development of vestigial
      tooth rudiments in the incisor and molar regions resulting in extra premolar-like
      teeth. The size and the degree of asymmetry of the continuously growing mouse
      incisor can be modulated by modifying the complex network of FGF, bone
      morphogenetic protein, and Activin signals, which regulate the proliferation and
      differentiation of epithelial stem cells. Follistatin, Sprouty, and Sostdc1 are
      important endogenous inhibitors antagonizing these pathways and they are also
      involved in regulation of enamel formation, and patterning of teeth in crown and
      root domains. All these findings support the hypothesis that the diversity of
      tooth types and dental patterns may have resulted from tinkering with the
      conserved signal pathways, organized into complex networks, during evolution.

PMID- 19156668
TI  - Onset and relapse of psychiatric disorders following early breast cancer: a case
      control study.
AB  - OBJECTIVE: Our objective is to evaluate the mental status of primary early breast
      cancer survivors according to DSM-IV criteria, distinguishing new psychiatric
      diagnosis, which started after the cancer diagnosis from relapse. METHODS: A
      comparative study of 144 breast cancer survivors and 125 women without previous
      history of cancer was carried out. Neuropsychiatric symptomatology was assessed
      retrospectively using standardized psychiatric examinations (Mini International
      Neuropsychiatric Interview, Watson's Post-Traumatic Stress Disorder Inventory)
      over three successive periods, 'before cancer' (from childhood to 3 years before
      the interview), 'around the cancer event' (the last 3 years including the time of
      diagnosis and treatment), and 'currently' (the last 2 weeks). RESULTS: Increased
      rates of anxiety and mood disorders were observed following a diagnosis of breast
      cancer compared with controls (generalized anxiety disorder (GAD) and major
      depressive disorder (MDD); 10.4 vs 1.6% and 19.4 vs 8.8%, respectively). The
      cancer disease promoted the development of dysthymia (n=4 new cases/6 two-year
      prevalent cases) and PTSD (7/7) and the re-emergence of MDD (n=21 relapses/28
      three-year prevalent cases) and GAD (10/15). No improvement in serious mood
      disorders such as MDD (16.0 vs 7.2%) and dysthymia (4.2 vs 0%) was reported at
      the time of interview, more than 1.75 years (median time) after the cancer
      surgery, the prevalence being 2-4 times greater in breast cancer survivors than
      in controls. CONCLUSION: Despite significant advances in treatment, a diagnosis
      of breast cancer is highly associated with various forms of psychopathology,
      regardless of psychiatric history, with symptoms persisting after treatment.
      These results may assist clinicians in planning mental healthcare for women with
      breast cancer.

PMID- 19156669
TI  - Pharmacodynamics of glucose regulation by methylprednisolone. II. normal rats.
AB  - A physiologic pharmacodynamic model was developed to jointly describe the effects
      of methylprednisolone (MPL) on adrenal suppression and glycemic control in normal
      rats. Six groups of animals were given MPL intravenously at 0, 10 and 50 mg/kg,
      or by subcutaneous 7 day infusion at rates of 0, 0.1 and 0.3 mg/kg/h. Plasma
      concentrations of MPL, corticosterone (CST), glucose and insulin were determined
      at various times up to 72 h after injection and 336 h after infusion. The
      pharmacokinetics of MPL was described by a two-compartment model. A circadian
      rhythm for CST was found in untreated rats with a stress-altered baseline caused
      by handling, which was captured by a circadian harmonic secretion rate with an
      increasing mesor. All drug treatments caused CST suppression. Injection of MPL
      caused temporary increases in glucose over 4 h. Insulin secretion was thereby
      stimulated yielding a later peak around 6 h. In turn, insulin can normalize
      glucose. However, long-term dosing caused continuous hyperglycemia during and
      after infusion. Hyperinsulinemia was achieved during infusion, but diminished
      immediately after dosing despite the high glucose concentration. The effects of
      CST and MPL on glucose production were described with a competitive stimulation
      function. A disease progression model incorporating reduced endogenous glucose
      uptake/utilization was used to describe glucose metabolism under different
      treatments. The results exemplify the roles of endogenous and exogenous hormones
      in mediating glucose dynamics. The pharmacokinetic/pharmacodynamic model is
      valuable for quantitating diabetogenic effects of corticosteroid treatments and
      provides mechanistic insights into the hormonal control of the metabolic system.

PMID- 19156670
TI  - Does informed decision making influence psychological outcomes after receiving a
      positive screening outcome?

PMID- 19156671
TI  - Retributive constraints on the concept of competency: the required role of
      'patently false beliefs' in understanding competency to be executed.

PMID- 19156672
TI  - A comparison of tests for restricted orderings in the three-class case.
AB  - A variety of methods for comparing three distributions have been proposed in the
      literature. These methods assess the same null hypothesis of equal distributions
      but differ in the alternative hypothesis they consider. The alternative
      hypothesis can be that measurements from the three classes are distributed
      according to unequal distributions or that measurements between the three classes
      follow a specific monotone ordering, an inverse-U-shaped (umbrella) ordering, or
      a U-shaped (tree) ordering. This paper compares these tests with respect to power
      and test size under different simulation scenarios. In addition, the methods are
      illustrated in two applications generated by different research questions with
      data from three classes suggesting monotone and umbrella orders. Additionally,
      proposals for the appropriate application of these tests are provided.

PMID- 19156673
TI  - Marginalized random effects models for multivariate longitudinal binary data.
AB  - Generalized linear models with random effects are often used to explain the
      serial dependence of longitudinal categorical data. Marginalized random effects
      models (MREMs) permit likelihood-based estimations of marginal mean parameters
      and also explain the serial dependence of longitudinal data. In this paper, we
      extend the MREM to accommodate multivariate longitudinal binary data using a new
      covariance matrix with a Kronecker decomposition, which easily explains both the
      serial dependence and time-specific response correlation. A maximum marginal
      likelihood estimation is proposed utilizing a quasi-Newton algorithm with quasi
      Monte Carlo integration of the random effects. Our approach is applied to analyze
      metabolic syndrome data from the Korean Genomic Epidemiology Study for Korean
      adults.

PMID- 19156674
TI  - Dental lamina as source of odontogenic stem cells: evolutionary origins and
      developmental control of tooth generation in gnathostomes.
AB  - This study considers stem cells for odontogenic capability in biological tooth
      renewal in the broad context of gnathostome dentitions and the derivation of them
      from oral epithelium. The location of the developmental site and cell dynamics of
      the dental lamina are parameters of a possible source for odontogenic epithelial
      stem cells, but the phylogenetic history is not known. Understanding the
      phylogenetic basis for stem cell origins throughout continuous tooth renewal in
      basal jawed vertebrates is the ultimate objective of this study. The key to
      understanding the origin and location of stem cells in the development of the
      dentition is sequestration of stem cells locally for programmed tooth renewal. We
      suggest not only the initial pattern differences in each dentate field but local
      control subsequently for tooth renewal within each family. The role of the
      specialized odontogenic epithelium (odontogenic band) is considered as that in
      which the stem cells reside and become partitioned. These regulate time, position
      and shape in sequential tooth production. New histological data for
      chondrichthyan fish show first a thickening of the oral epithelium (odontogenic
      band). After this, all primary and successive teeth are only generated deep to
      the oral epithelium from a dental lamina. In contrast, in osteichthyan fish the
      first teeth develop directly within the odontogenic band. In addition, successors
      are initiated at each tooth site in the predecessor tooth germ (without a dental
      lamina). We suggest that stem cells specified for each tooth family are set up
      and located in intermediate cells between the outer and inner dental epithelia.

PMID- 19156675
TI  - Long-term cancer survivors experience work changes after diagnosis: results of a
      population-based study.
AB  - BACKGROUND: Although cancer survivorship is increasing with improved diagnosis
      and treatments, few studies have explored employment changes and the factors
      related to this change among cancer survivors. Therefore, we aim to explore the
      prevalence of employment problems in long-term cancer survivors. In addition, we
      explored what patient or tumour characteristics predicted employment changes.
      METHODS: All 1893 long-term survivors of prostate cancer, endometrial cancer, non
      Hodgkin's lymphoma, and Hodgkin's lymphoma diagnosed between 1989 and 1998 in the
      area of the Comprehensive Cancer Centre South, The Netherlands were included in a
      population-based cross-sectional survey. RESULTS: Response rate was 80% (n=1511).
      After excluding survivors without a job before diagnosis, 403 survivors remained;
      197 (49%) experienced no changes in their work situation following cancer
      diagnosis, 69 (17%) were working fewer hours, and 137 (34%) stopped working or
      retired. A medium educational level was significant in reducing the risk of work
      changes. Being older, having more than one comorbid condition, being treated with
      chemotherapy, and disease progression were significant independent predictors of
      work changes after cancer. Experiencing work changes was associated with lower
      physical functioning but positively associated with social well-being.
      DISCUSSION: Long-term cancer survivors experience work changes after diagnosis
      and treatment, and clinical factors significantly predicted work change after
      cancer. As such, our study underscores the importance of rehabilitation programs
      in improving the return to work after cancer.

PMID- 19156676
TI  - Political orientation and perceptions of adolescent autonomy and judicial
      culpability.
AB  - This study probed general attitudes about processing youths in adult criminal
      court across a range of offenses, explored attitudes about age of autonomous
      decision-making for several activities outside the criminal justice context, and
      examined the interaction between these two realms. The major finding was that
      adults favor adult punishment of adolescent offenders at younger ages than they
      favor autonomy in other decision-making contexts; the gap is widest for those who
      identify themselves as conservatives.

PMID- 19156677
TI  - Violent offenses associated with co-occurring substance use and mental health
      problems: evidence from CJDATS.
AB  - The present study examines the relationship between substance use, mental health
      problems, and violence in a sample of offenders released from prison and referred
      to substance abuse treatment programs. Data from 34 sites (n = 1,349) in a
      federally funded cooperative, the Criminal Justice Drug Abuse Treatment Studies
      (CJDATS), were analyzed. Among parolees referred to substance abuse treatment,
      self-reports for the six-month period before the arrest resulting in their
      incarceration revealed frequent problems with both substance use and mental
      health. For most offenders with substance use problems, the quantity of alcohol
      consumed and the frequency of drug use were associated with a greater probability
      of self-reported violence. Mental health problems were not indicative of
      increases in violent behavior, with the exception of antisocial personality
      problems, which were associated with violence. The paper emphasizes the
      importance of providing substance abuse treatment in relation to violent behavior
      among offenders with mental health problems being discharged to the community.

PMID- 19156678
TI  - A latent class factor approach to identifying subtypes of juvenile diversion
      youths based on psychopathic features.
AB  - Latent class factor analysis allows for the estimation of a dimensional construct
      such as psychopathy through factor analysis while also examining the
      heterogeneity of the sample. We report the results of a latent class factor
      analysis examining the psychometric structure of a widely used measure of
      psychopathy, as well as internalizing (i.e. anxiety) and externalizing indices,
      among diversion program youths involved in an intervention study. The results
      indicated that four subgroups of adolescents existed in the data: one with high
      psychopathic features and externalizing problems, but low anxiety; one with
      moderately high affective and behavioral psychopathic features and externalizing
      problems, but low anxiety; one with moderately high interpersonal and behavioral
      psychopathic features, externalizing problems, and anxiety; and one with very low
      psychopathy scores, anxiety, and externalizing problems. The validity of these
      subgroups was assessed comparing prior family problems, substance use, and
      offending measures, and one-year follow-up measures of recidivism, detention
      days, substance use, and program completion. This study offers partial support
      for the existence of psychopathy subgroups and has implications for future
      studies of psychopathy typologies. In addition, this study employed a methodology
      for classification that permits consideration of the dimensional nature of a
      construct, and as such has implications for a variety of research areas.

PMID- 19156679
TI  - Deterring malingered psychopathology: The effect of warning simulating
      malingerers.
AB  - The utility of a warning to deter malingering on measures of personality and
      psychopathology was examined. Sixty-seven first year psychology students were
      randomly assigned to one of three conditions: unwarned malingerers, warned
      malingerers, and controls. Participants in the two malingering groups were given
      a financial incentive to simulate believable psychological impairment. Warned
      malingerers received an additional warning that the tests could detect
      malingering and that detection would result in loss of course credit. Controls
      received standardized test instructions. It was hypothesized that the malingering
      incentive would be sufficient to induce malingering, but that a deterrence theory
      warning would have a subsequent deterrent effect. Between-groups analyses
      indicated that the warning used in this study significantly altered test
      performance on the Personality Assessment Inventory (PAI) and revised Symptom
      Checklist 90 (SCL-90-R). Warned malingerers scored significantly lower (faked
      less) than unwarned malingerers on the majority of the psychopathology scales and
      frequently approximated control group performances. These results support the
      effectiveness of a warning to complement existing malingering detection methods.

PMID- 19156684
TI  - Risk factors for suicide following hospital discharge among cancer patients.
AB  - OBJECTIVES: This study aims to examine risk factors associated with 3-month post
      discharge suicide among cancer patients using Taiwan's nationwide, population
      based datasets. METHODS: The study cohort comprised all cancer patients
      discharged from hospitals from 2002 to 2004, inclusive, who committed suicide
      within 90 days of discharge (n=311). The control group consisted of 1555 cancer
      patients who did not commit suicide within 90 days of discharge. The dependent
      variable was whether or not a patient committed suicide within 90 days of
      discharge, while the independent variables included patient, hospital and
      physician characteristics at index hospitalization. Cox proportional hazard
      regression was carried out to compute the 90-day survival rate, adjusting for
      possible confounding factors. RESULTS: The mean interval from discharge to
      suicide was 39.7 days (+/-95.2) and almost half (46.3%) of the 3-month post
      discharge suicides occurred within 14 days after discharge. The adjusted hazard
      of committing suicide for patients who were not hospitalized in the preceding
      year was 1.68 (p=0.009), 1.61 (p=0.033), and 2.51 (p<0.001) times greater,
      respectively, than patients who were hospitalized once, twice and more than twice
      within the year before index hospitalization. The hazard of committing suicide
      among patients who were unemployed was 1.71 (p<0.001) times that of their
      employed counterparts. CONCLUSIONS: We conclude that, while our study was limited
      to suicides among cancer patients within 90 days of discharge, around 60% of
      deaths occurred within the first month after discharge. The relevant risk factors
      include the number of hospitalizations within 1 year and employment status.

PMID- 19156680
TI  - Maltreated children's understanding of and emotional reactions to dependency
      court involvement.
AB  - Little is known about the extent to which maltreated children understand what is
      happening during their participation in court proceedings, despite large numbers
      of children coming into contact with the legal system as victims of maltreatment.
      In the present study, maltreated 4- to 15-year-olds were interviewed about their
      understanding of dependency court on the day of their scheduled court visit.
      Their feelings about attending their hearings were also assessed, and after their
      hearing, their understanding of the decisions was examined. Age-related
      improvements in children's understanding emerged. Also, children who were more
      knowledgeable about the legal system were less distressed about attending their
      hearings, as were younger children who had been in the system a longer time.
      Finally, a majority of children lacked full or accurate understanding of what
      actually happened during their hearings. Findings have implications for
      children's participation in legal proceedings and the development of
      interventions to facilitate children's legal understanding.

PMID- 19156685
TI  - Contribution of fetal cerebral MRI for diagnosis of structural anomalies.
AB  - More than 20 years after its introduction, magnetic resonance imaging (MRI) is
      now considered a useful complementary tool in the imaging work-up of fetal brain
      structural anomalies, but its real contribution in neuro-fetal imaging is still
      controversial. Our purpose is to present an overview of the most valuable
      indications of fetal cerebral MRI in current practice as guided by dedicated
      ultrasound analysis. On the basis of a review of the literature and our personal
      experience, we underline herein the real complementarities between these two
      techniques in different clinical or imaging settings and show how MRI adds
      significant information compared with ultrasound, especially in the late second
      and third trimesters. We assess the interest of using MRI from a technical point
      of view (complete and extensive anatomical analysis, analysis of developmental
      and pathological processes) and from a practical point of view in different
      imaging and clinical settings.

PMID- 19156686
TI  - In vivo quantification of blood velocity in mouse carotid and pulmonary arteries
      by ECG-triggered 3D time-resolved magnetic resonance angiography.
AB  - Blood flow velocity is a functional parameter of fundamental importance in
      diagnosis and follow-up of various vascular diseases. Vascular pathologies can be
      efficiently studied in animal models, especially in small rodents. ECG-gated
      magnetic resonance imaging (MRI) assessment of blood velocity in small animals is
      a challenge because of limited spatial resolution and high-frequency
      physiological parameters. Here it is shown that a bright-blood cine-3D-MRI method
      can be used to measure blood velocity at specific times of the cardiac cycle in
      mouse pulmonary and carotid arteries. The method used a series of time-of-flight
      (TOF) acquisitions in a volume of interest at different times after signal
      cancellation in the same volume. This scheme was repeated at different periods of
      the cardiac cycle by varying the delay between the ECG R-wave peak and signal
      cancellation. Velocity values in mouse pulmonary artery varied from 35 cm/s in
      systole to 0-10 cm/s in diastole. A similar pattern was displayed in carotid
      arteries (18 and 2.5 cm/s, in systole and diastole, respectively). Results are
      discussed in terms of efficiency, limitation, and comparison with other methods.

PMID- 19156687
TI  - Expression of Brachyury in mesenchymal progenitor cells leads to cartilage-like
      tissue that is resistant to the destructive effect of rheumatoid arthritis
      synovial fibroblasts.
AB  - Our objectives were to determine the chondrogenic potential of a murine Brachyury
      transformed mesenchymal progenitor cell line in the presence of rheumatoid
      arthritis-activated synovial fibroblasts (RASFs). Brachyury-transformed
      mesenchymal progenitor cells were implanted alone or combined with RASFs isolated
      from diseased human joints in each of six immunodeficient SCID mice. De novo
      tissue formation was analysed by histology and immunohistochemistry after 60
      days. Spheroid nodules resembling cartilage morphologically and by the expression
      of proteoglycans and collagen II developed in four of six implants in the absence
      and in five of six implants in the presence of RASFs. No evidence for
      hypertrophic differentiation could be observed. Mesenchymal progenitor cells
      transformed with Brachyury are able to produce a cartilage like tissue in vivo
      over an extended period of time that is resistant to the destructive effect of
      RASF. This observation may provide opportunities for a cell-based reconstructive
      treatment in joint disease.

PMID- 19156688
TI  - Uracil as nucleating agent for bacterial poly[(3-hydroxybutyrate)-co-(3
      hydroxyhexanoate)] copolymers.
AB  - In this study, uracil has been introduced as the nucleating agent (NA) for
      bacterially synthesized poly[(3-hydroxybutyrate)-co-(3-hydroxyhexanoate)]
      (PHBHHx) copolymers with HHx content of 5, 10, 18 mol-%, and poly(3
      hydroxybutyrate) (PHB) homopolymer for the first time. Its effect was compared
      with the conventional NA of PHB, that is, boron nitride (BN), and two other
      naturally occurring pyrimidine derivatives, i.e., thymine and cytosine. The
      effects of uracil on the crystallization kinetics, melting behavior, spherulite
      morphology, and crystalline structure of PHBHHx and PHB were investigated by
      differential scanning calorimetry (DSC), polarized optical microscopy (POM), and
      wide-angle X-ray diffraction (WAXD). Uracil and BN exhibit the comparable
      nucleation efficiency on the crystallization of PHB, whereas uracil shows much
      more effective nucleation ability than BN for PHBHHx copolymers. With
      incorporation of 1 wt.-% uracil, PHBHHx with 0-10 mol-% HHx units can finish
      crystallization upon cooling at 10 degrees C x min(-1). The crystallization half
      times (t(1/2)) of all the PHB and PHBHHx samples decrease significantly with
      presence of uracil. The crystallization rate of polymers further enhances with
      increase in uracil concentration. With addition of 1 wt.-% uracil, the t(1/2)
      value of PHBHHx with 10 mol-% HHx units melt-crystallizing at 80 degrees C
      decreases to approximately 4.0% of the neat polymer, and the nucleation density
      increases by 3-4 orders of magnitude. The incorporation of uracil has no
      discernable effect on the crystalline structure of PHBHHx, as evidenced by WAXD
      results. It was proposed that the nucleation mechanism of the uracil/PHBHHx (or
      PHB) system might be the epitaxial nucleation.

PMID- 19156689
TI  - Effect of head size in head-tail-type polycations on their in vitro performances
      as nonviral gene vectors.
AB  - Three kinds of head-tail-type block copolymers composed of polyamidoamine (PAMAM)
      dendron heads and poly(L-lysine) (PLL) tail blocks (PAMAM dendron-PLL), having
      PAMAM dendrons with different generations (G2.5-PLL, G3.5-PLL and G4.5-PLL) were
      synthesized. Some of the dendron heads were located at polyplex surface, and G2.5
      PLL and G3.5-PLL could form small polyplexes (less than 150 nm in size). G2.5-PLL
      and G3.5-PLL polyplexes were taken up into the cells more effectively. PAMAM
      dendron-PLL that had a larger dendron head could show a more-effective buffering
      effect. The in vitro performance of the PAMAM dendron-PLL polyplexes was
      controlled by the balance of cellular uptake and endosomal escape by a buffering
      effect.

PMID- 19156692
TI  - We've got chemistry sussed.

PMID- 19156693
TI  - From Chem. Eur. J. to ChemSusChem: all from ChemPubSoc Europe.

PMID- 19156694
TI  - Autothermal catalytic partial oxidation of glycerol to syngas and to non
      equilibrium products.
AB  - Glycerol, a commodity by-product of the biodiesel industry, has value as a fuel
      feedstock and chemical intermediate. It is also a simple prototype of sugars and
      carbohydrates. Through catalytic partial oxidation (CPOx), glycerol can be
      converted into syngas without the addition of process heat. We explored the CPOx
      of glycerol using a nebulizer to mix droplets with air at room temperature for
      reactive flash volatilization. Introducing this mixture over a noble-metal
      catalyst oxidizes the glycerol at temperatures over 600 degrees C in 30-90 ms.
      Rhodium catalysts produce equilibrium selectivity to syngas, while platinum
      catalysts produce mainly autothermal non-equilibrium products. The addition of
      water to the glycerol increases the selectivity to H(2) by the water gas shift
      reaction and reduces non-equilibrium products. However, water also quenches the
      reaction, resulting in a maximum in H(2) production at a steam/carbon ratio of
      2:3 over a Rh-Ce catalyst. Glycerol without water produces a variety of chemicals
      over Pt, including methylglyoxal, hydroxyacetone, acetone, acrolein,
      acetaldehyde, and olefins.

PMID- 19156695
TI  - Gated dynamic 31P MRS shows reduced contractile phosphocreatine breakdown in mice
      deficient in cytosolic creatine kinase and adenylate kinase.
AB  - We developed a new dedicated measurement protocol for dynamic (31)P MRS analysis
      in contracting calf muscles of the mouse, using minimally invasive assessment of
      the contractile force combined with the acquisition of spectroscopic data gated
      to muscle contraction and determination of phosphocreatine (PCr) recovery rate
      and ATP contractile cost. This protocol was applied in a comparative study of six
      wild type (WT) mice and six mice deficient in cytosolic creatine kinase and
      adenylate kinase isoform 1 (MAK(-/-) mice) using 70 repeated tetanic contractions
      at two contractions per minute. Force levels during single contractions, and
      metabolite levels and tissue pH during resting conditions were similar in muscles
      of MAK(-/-) and WT mice. Strikingly, muscle relaxation after contraction was
      significantly delayed in MAK(-/-) mice, but during repeated contractions, the
      decrease in the force was similar in both mouse types. Gated data acquisition
      showed a negligible PCr breakdown in MAK(-/-) immediately after contraction,
      without a concomitant decrease in ATP or tissue pH. This protocol enabled the
      determination of rapid PCr changes that would otherwise go unnoticed due to
      intrinsic low signal-to-noise ratio (SNR) in mouse skeletal muscles combined with
      an assessment of the PCr recovery rate. Our results suggest that MAK(-/-) mice
      use alternative energy sources to maintain force during repeated contractions
      when PCr breakdown is reduced. Furthermore, the absence of large increases in
      adenosine diphosphate (ADP) or differences in force compared to WT mice in our
      low-intensity protocol indicate that creatine kinase (CK) and adenylate kinase
      (AK) are especially important in facilitating energy metabolism during very high
      energy demands.

PMID- 19156696
TI  - Modulation of choline kinase activity in human cancer cells observed by dynamic
      31P NMR.
AB  - Choline metabolites are widely studied in cancer research as biomarkers of
      malignancy and as indicators of therapeutic response. However, endogenous
      phosphocholine levels are determined by a number of processes that confound the
      interpretation of these measurements, including membrane transport rates and a
      series of enzyme catalysed reactions in the Kennedy pathway. Employing a dynamic
      (31)P NMR assay that is specific to choline kinase (ChoK) we have measured the
      rates of this enzyme reaction in cell lysates of MDA-MB-231 breast, PC-3 prostate
      and HeLa cervical cancer cells and in solutions of purified human ChoK. The rates
      are sensitive to inhibition by hemicholinium-3 (HC-3), a competitive ChoK
      inhibitor, and to N-[2-bromocinnamyl(amino)ethyl]-5-isoquinolinesulphonamide (H
      89), an agent commercialized as a specific cyclic-AMP-dependent protein kinase A
      (PKA) inhibitor.

PMID- 19156698
TI  - How to evaluate the calibration of a disease risk prediction tool.
AB  - To evaluate the calibration of a disease risk prediction tool, the quantity E/O,
      i.e. the ratio of the expected to the observed number of events, is usually
      computed. However, because of censoring, or more precisely because of individuals
      who drop out before the termination of the study, this quantity is generally
      unavailable for the complete population study and an alternative estimate has to
      be computed. In this paper, we present and compare four methods to do this. We
      show that two of the most commonly used methods generally lead to biased
      estimates. Our arguments are first based on some theoretic considerations. Then,
      we perform a simulation study to highlight the magnitude of biases. As a
      concluding example, we evaluate the calibration of an existing predictive model
      for breast cancer on the E3N-EPIC cohort.

PMID- 19156697
TI  - MRSI and DTI: a multimodal approach for improved detection of white matter
      abnormalities in alcohol and nicotine dependence.
AB  - Our previous proton magnetic resonance spectroscopic imaging ((1)H MRSI) studies
      showed that the frontal lobe white matter (WM) in smoking recovering alcoholics
      (sRA) had lower concentrations of N-acetylaspartate (NAA), a marker for neuron
      viability, compared to both nonsmoking recovering alcoholics (nsRA) and a control
      group of nonsmoking light drinkers (nsLD). Using diffusion tensor imaging (DTI)
      in a similar population, we found lower fractional anistropy (FA), a
      microstructural measure of WM fiber integrity, in regions of specific fiber
      bundles within frontal WM of recovering alcoholics compared to light drinkers. In
      this study, we hypothesized that in these regions of lower FA, NAA concentrations
      in the alcoholic groups are lower than in non-alcoholic controls. We hypothesized
      further that sRA have lower regional NAA concentrations than nsRA. We
      retrospectively analyzed existing (1)H MRSI data by quantitating metabolite
      concentrations from voxels that corresponded to previously identified WM regions
      of lower FA, and from a control region of normal FA in alcoholics. We found
      significant NAA concentration differences between groups in regions of abnormal
      FA. In particular, sRA had significantly lower NAA concentration than nsLD, but
      in no region was NAA significantly lower in nsRA than nsLD. Furthermore, no NAA
      group differences were detected in a frontal WM region of normal FA. These
      results indicate regionally localized NAA loss within the frontal WM, and
      specifically NAA loss in regions of low FA. Compared to our previous lobar
      analyses, DTI-guided MRSI analysis allows the selective evaluation of small WM
      regions with microstructural injury, thereby increasing statistical power to
      detect relevant pathology and group differences. DTI-guided MRSI analyses promise
      to contribute to a better understanding of brain injury in alcohol and nicotine
      dependence and, by extension, perhaps in other neurodegenerative diseases as
      well.

PMID- 19156699
TI  - Association between cognition and daily life functioning in dementia subtypes.
AB  - OBJECTIVE: To investigate the association between cognition and daily life
      functioning in dementia subtypes. METHODS: Cross-sectional data were used from
      615 patients with dementia who were referred to the Maastricht Memory Clinic of
      the Maastricht University Medical Centre. Pearson correlation coefficients were
      calculated between the Mini-Mental State Examination (MMSE; to measure cognitive
      status) and the Blessed Dementia Scale (BDS; to measure daily life functioning)
      for the following types of dementia: Alzheimer's Disease (AD, n = 442); Vascular
      dementia (VaD, n = 113); frontotemporal dementia (FTD, n = 18); Parkinson's
      dementia (PD, n = 21); and primary progressive aphasia (PPA, n = 21). One-way
      ANOVA was used to test differences in age, MMSE scores and BDS scores across
      dementia subtypes. RESULTS: Scores on the MMSE showed strong correlation with BDS
      scores in cases of FTD (r = -0.80); moderate correlation in cases of AD, VaD, and
      PD (range r = -0.50-0.60); while no correlation was found in PPA cases.
      CONCLUSIONS: The association between cognition and daily life functioning varied
      among dementia subtypes for AD, VaD, FTD and PD. Furthermore, the overall scores
      on both domains differ between dementia subtypes, indicating that different types
      of dementia are characterized by a specific pattern of cognitive status and daily
      life functioning. These findings underline the need for multidomain assessment in
      patients with dementia.

PMID- 19156700
TI  - Expert opinion on the management of behavioural and psychological symptoms of
      dementia (BPSD) and investigation into prescribing practices in the UK.
AB  - BACKGROUND: The management of Behavioural and Psychological Symptoms of Dementia
      (BPSD) has been the subject of considerable debate over the last few years in
      view of the poor evidence base for pharmacological agents and concerns about
      their safety. OBJECTIVES: This study sought to obtain expert opinion on the
      management of BPSD and to investigate current prescribing practices in the UK.
      METHOD: A total of 166 expert opinion surveys were emailed to UK consultants in
      Old Age Psychiatry asking them to rate the appropriateness of psychotropics in
      different aspects of BPSD. A service evaluation was also carried out in 8 UK
      centres to investigate prescribing patterns. RESULTS: Overall, 59 consultants
      returned completed questionnaires, a response rate of 35%. Results revealed that
      experts rated quetiapine as the most appropriate agent for all BPSD followed by
      acetylcholinesterase inhibitors for psychotic symptoms, benzodiazepines for
      agitation or aggression and trazodone for behavioural symptoms such as
      disinhibition. The service evaluations showed that benzodiazepines were most
      frequently prescribed for BPSD. CONCLUSIONS: Although quetiapine was judged by
      experts to be the most appropriate agent for BPSD, it appears that in clinical
      practice benzodiazepines are most often used to manage these symptoms. Evidence
      from both studies show wide inconsistencies in prescribing trends.

PMID- 19156701
TI  - The impact of personal characteristics on engagement in nursing home residents
      with dementia.
AB  - OBJECTIVE: To examine the impact of personal attributes on engagement in persons
      with dementia. METHODS: Participants were 193 residents of seven Maryland nursing
      homes. All participants had a diagnosis of dementia. Cognitive functioning was
      assessed via the Mini-Mental State Examination, and engagement was assessed via
      the Observational Measure of Engagement. Data pertaining to activities of daily
      living were obtained from the Minimum Data Set. RESULTS: Women had longer mean
      engagement duration than men, and significant results were not seen with the
      other demographic variables. Significant, positive correlations were found
      between higher cognitive functioning and longer engagement duration, more
      attention, a more positive attitude, and a higher refusal rate. There was a
      positive and significant correlation between the comorbidity index and engagement
      duration, and between the number of medications and attention. All functional
      status variables yielded significance in a positive direction. Participants with
      poor hearing had a higher refusal rate. Cognitive status was the most consistent
      and potent predictor of engagement in this population. CONCLUSION: Despite a
      higher refusal rate among those with higher cognitive levels, their overall
      engagement with stimuli is higher. Caregivers should anticipate higher refusal
      rates in those with poor hearing, and therefore compensatory methods should be
      used in presenting stimuli in this population. The potent role of cognitive and
      functional status on engagement of persons with dementia underscores the
      importance of tailoring activities to nursing home residents' needs, interests,
      and limitations.

PMID- 19156702
TI  - Lack of association between antipsychotic-induced Parkinsonism or its subsymptoms
      and rs4606 SNP of RGS2 gene in African-Caribbeans and the possible role of the
      medication: the Curacao extrapyramidal syndromes study X.
AB  - Recent studies demonstrate an association between antipsychotic-induced
      parkinsonism (AIP) and rs4606 SNP of RGS2 gene in Jewish and African-Americans.
      The current study investigates the association between rs4606 and AIP or its
      subsymptoms (rest tremor, rigidity, and bradykinesia) in 112 psychiatric
      inpatients of African-Caribbean origin. Presence of AIP, rigidity, bradykinesia,
      and tremor was measured by the UPDRS. We applied chi(2) (or Fisher Exact) and
      logistic regression analyses in several models including rs4606, age, gender,
      dose of antipsychotics, and anticholinergics, and two other putatively functional
      SNPs in DRD2 (-141CIns/Del) and HTR2C (Cys23Ser) genes. In contrast to recent
      literature, we find no evidence for an association between rs4606 and AIP or any
      of its subsymptoms. We hypothesize that the observed lack of association is due
      probably to differences in serotonin 2A-receptor affinities of the antipsychotics
      utilized (in contrast to the other published studies, the majority of our
      patients utilized typical antipsychotics).

PMID- 19156703
TI  - In situ observation of oxidation of liquid droplets of tin and melting behavior
      of a tin particle covered with a tin oxide layer.
AB  - Oxidation of a liquid droplet of tin (Sn) was observed using an in situ specimen
      heating holder in an oxygen environment. The surface of the Sn liquid droplet was
      covered with a tin oxide layer, Sn(3)O(4), the thickness of which depended on the
      oxygen pressure and temperature. Subsequent cooling of the droplet resulted in
      the formation of a solid Sn particle covered with a Sn(3)O(4) layer. The solid Sn
      particle was then heated above the melting temperature of Sn, and the melting
      behavior of Sn was observed.

PMID- 19156704
TI  - The Hall-Petch law investigated by means of in situ straining experiments in
      lamellar TiAl and deformed Al.
AB  - Dislocation-boundary interactions are studied in TiAl and Al by means of in situ
      straining experiments in transmission electron microscopes (TEM). The results in
      TiAl allow us to measure the strength of domain boundaries against the motion of
      ordinary dislocations and twins. The results in Al are used to analyze the
      interaction between dislocations and cell walls. Parameters involved in the Hall
      Petch law are then deduced from these observations.

PMID- 19156705
TI  - Relationship between HbA1c and hypoglycaemia in patients with type 2 diabetes
      treated with different insulin regimens in combination with metformin.
AB  - BACKGROUND: To examine the relationship between glycaemic control and
      hypoglycaemia in patients with type 2 diabetes treated with metformin (Met) and
      either insulin lispro mixtures, given twice or thrice daily (LM + Met), or
      insulin glargine, given once daily (G + Met). METHODS: Data from three randomized
      clinical trials were pooled to compare effects of LM + Met with G + Met. RESULTS:
      The LM + Met group achieved lower mean HbA(1c) (mean+/-SE, 7.2+/-0.1 vs. 7.7+/
      0.1%, p<0.0001) and all meals combined post-prandial blood glucose (BG) (8.9+/
      0.1 vs. 10.2+/-0.1 mmol/L, p<0.0001) compared with the G + Met group, but had
      higher fasting blood glucose (8.1+/-0.1 vs. 6.8+/-0.1 mmol/L, p<0.0001) and
      insulin requirement (0.7+/-0.01 vs. 0.6+/-0.01 U/kg, p<0.0001). Over the entire
      study period, daytime hypoglycaemia was higher for the LM + Met group (10.3 vs.
      3.5 episodes/patient/year, p<0.0001) than for the G + Met group; however,
      nocturnal hypoglycaemia was lower (3.4 vs. 6.6 episodes/patient/year, p=0.003).
      At endpoint, daytime hypoglycaemia was higher for the LM + Met group (6.2 vs. 1.4
      episodes/patient/year, p<0.0001); however, nocturnal hypoglycaemia was similar in
      both groups (1.9 vs. 3.0 episodes/patient/year). An inverse relationship was
      observed between all confirmed hypoglycaemia and HbA(1c) at endpoint; for every
      1% reduction in HbA(1c), the increase (in slope) was 1.4 episodes/patient/year
      (p=0.04). Patients with confirmed hypoglycaemia had lower HbA(1c) than patients
      without hypoglycaemia (7.39 vs. 7.64%, respectively; decrement=0.26%, p=0.026).
      CONCLUSIONS: These studies demonstrated an inverse relationship between HbA(1c)
      and 24-h and daytime hypoglycaemia. Lispro insulin mixtures provided lower
      HbA(1c) and post-prandial blood glucose values than glargine, but caused more
      daytime hypoglycaemia. Frequency of nocturnal hypoglycaemia was similar and
      severe hypoglycaemia was rare with both insulin regimens.

PMID- 19156706
TI  - Classification and basic properties of contrast agents for magnetic resonance
      imaging.
AB  - A comprehensive classification of contrast agents currently used or under
      development for magnetic resonance imaging (MRI) is presented. Agents based on
      small chelates, macromolecular systems, iron oxides and other nanosystems, as
      well as responsive, chemical exchange saturation transfer (CEST) and
      hyperpolarization agents are covered in order to discuss the various
      possibilities of using MRI as a molecular imaging technique. The classification
      includes composition, magnetic properties, biodistribution and imaging
      applications. Chemical compositions of various classes of MRI contrast agents are
      tabulated, and their magnetic status including diamagnetic, paramagnetic and
      superparamagnetic are outlined. Classification according to biodistribution
      covers all types of MRI contrast agents including, among others, extracellular,
      blood pool, polymeric, particulate, responsive, oral, and organ specific
      (hepatobiliary, RES, lymph nodes, bone marrow and brain). Various targeting
      strategies of molecular, macromolecular and particulate carriers are also
      illustrated.

PMID- 19156707
TI  - Tone perception results with Harmony and HiRes 120 in Cantonese-speaking
      subjects.
AB  - The goal of this study was to examine tonal language perception in adults with
      cochlear implants who are native speakers of Cantonese. Ten adult subjects were
      implanted with HiRes 90K devices and participated in the study. Baseline data
      were obtained with standard HiRes and compared with HiRes 120. Subjects were
      evaluated using a tone identification test and a questionnaire. While objective
      outcome measures with the tone identification test did not show significant
      differences between standard HiRes and HiRes 120, subjective evaluation with the
      questionnaire showed significant differences in the overall satisfaction
      perceived by subjects. HiRes 120 received a significantly higher rating and the
      majority of subjects preferred HiRes 120.

PMID- 19156708
TI  - Endoscopic laser coagulation of feeding vessels in large placental
      chorioangiomas: report of three cases and review of invasive treatment options.
AB  - OBJECTIVE: To report three cases of large placental chorioangiomas managed with
      endoscopic laser coagulation of the feeding vessels, and review the literature
      regarding cases of chorioangioma treated with invasive techniques. METHODS:
      Intrauterine endoscopic surgery was performed using a 2.5-mm fetoscope under
      epidural anesthesia. Coagulation of the feeding vessels was attempted with laser
      energy, and the operation was completed with amniodrainage. RESULTS: The feeding
      vessels were successfully coagulated in one case, resulting in a term delivery.
      Histopathologic examination of the placenta confirmed a capillary chorioangioma
      with extensive necrosis. There were intraoperative complications in the other two
      cases, including bleeding at the site of coagulation requiring intrauterine
      transfusion in one, and incomplete vascular ablation in the other. In the former
      case the infant was born prematurely and developed chronic renal insufficiency.
      In the latter, the fetus died within the first week of the surgery. CONCLUSIONS:
      There are limited interventions available for the management of large,
      symptomatic placental chorioangiomas. Although they can be treated with
      endoscopic laser coagulation of the feeding vessels, fetal bleeding,
      exsanguination, and death are potential complications of the procedure;
      therefore, this technique should be used with caution. The role of this treatment
      modality in the early devascularization of placental chorioangiomas prior to the
      development of significant complications warrants consideration.

PMID- 19156709
TI  - Effect of augmented atypical antipsychotics on weight change in patients with
      major depressive disorder in a naturalistic setting.
AB  - OBJECTIVE: The extent of weight changes in depressed patients who use atypical
      antipsychotics (AAP) as augmentation could not be easily predicted due to weight
      related symptoms of depression and the interaction with antidepressants which
      have weight reducing effects. METHODS: Patients were treated with either
      antidepressants augmented with AAP for more than 2 weeks (AAP group, n = 100) or
      only with antidepressants (non-AAP group, n = 172) during the admission between
      2002 and 2006, and the differences in weight were analyzed. RESULTS: Mean weight
      gains of AAP group were significantly higher than those of non-AAP group (2.98 +/
      1.87 kg vs. 1.70 +/- 1.85 kg, p = 0.001). When stratified by antidepressants,
      the significant difference between the two groups was shown among the subjects
      who had taken serotonin reuptake inhibitors (SSRIs), but not mirtazapine and
      venlafaxine (3.42 +/- 2.01 kg vs. 1.48 +/- 1.79 kg, p < 0.001). Comparing among
      different combinations in AAP group showed that subjects treated with SSRIs and
      olanzapine had the greatest weight gain (4.21 +/- 1.90 kg), significantly higher
      than that of the other subgroups (p < 0.001). CONCLUSIONS: Our findings suggest
      that AAP used in patients with depression could severely aggravate preexisting
      weight-related problems of antidepressants use and the possibility that the
      combined use with specific antidepressants could have a unique effect on weight
      by drug-drug interactions.

PMID- 19156710
TI  - In vivo acute toxicity of titanium dioxide nanoparticles to mice after
      intraperitioneal injection.
AB  - Because of its excellent optical performance and electrical properties, TiO2 has
      a wide range of applications in many fields. It is often considered to be
      physiologically inert to humans. However, some recent studies have reported that
      nano-sized TiO2 may generate potential harm to the environment and humans. In
      this paper the in vivo acute toxicity of nano-sized TiO2 particles to adult mice
      was investigated. Mice were injected with different dosages of nano-sized TiO2
      (0, 324, 648, 972, 1296, 1944 or 2592 mg kg(-1)). The effects of particles on
      serum biochemical levels were evaluated at various time points (24 h, 48 h, 7
      days and 14 days). Tissues (spleen, heart, lung, kidney and liver) were collected
      for titanium content analysis and histopathological examination. Treated mice
      showed signs of acute toxicity such as passive behavior, loss of appetite, tremor
      and lethargy. Slightly elevated levels of the enzymes alanine aminotransferase
      and aspartate aminotransferase were found from the biochemical tests of serum
      whereas blood urea nitrogen was not significantly affected (P < 0.05). The
      accumulation of TiO2 was highest in spleen (P < 0.05). TiO2 was also deposited in
      liver, kidney and lung. Histopathological examinations showed that some TiO2
      particles had entered the spleen and caused the lesion of spleen. Thrombosis was
      found in the pulmonary vascular system, which could be induced by the blocking of
      blood vessels with TiO2 particles. Moreover, hepatocellular necrosis and
      apoptosis, hepatic fibrosis, renal glomerulus swelling and interstitial pneumonia
      associated with alveolar septal thickening were also observed in high-dose
      groups.

PMID- 19156712
TI  - Ileal and faecal digestibility of daidzein and genistein and plasma
      bioavailability of these isoflavones and their bioactive metabolites in the
      ovariectomised rat.
AB  - Consumption of the soya isoflavones genistein and daidzein may provide protection
      against postmenopausal bone loss. The purpose of this study was to determine
      ileal and faecal digestibility of daidzein and genistein and the extent of
      formation of metabolites in the gastrointestinal (GI) tract in the ovariectomised
      rat, a model for postmenopausal bone loss. Twenty female rats were ovariectomised
      and fed either genistein or daidzein (0.026% of diet) for 4 wks. Genistein,
      daidzein and their GI-derived metabolites were quantitatively determined in
      plasma, urine, faeces and ileal digesta using GC/MS. Ileal and faecal
      digestibility of genistein (93 and 99.9%, respectively) were significantly
      greater than that of daidzein (32 and 77.5%, respectively). In genistein
      supplemented animals, 4-ethylphenol was present in plasma in relatively high
      concentrations. The bioactivity of 4-ethylphenol may contribute to the
      physiological effects attributed to genistein consumption. The daidzein
      metabolite equol, was present in relatively high amounts in ileal digesta
      indicating substantial biotransformation of daidzein occurred in the small
      intestine presumably as a result of the activity of the resident microbiota.
      Further studies are required to determine whether 4-ethylphenol is a major
      metabolite of genistein in humans and the extent of biotransformation of daidzein
      to equol in the small intestine in humans.

PMID- 19156713
TI  - Silibinin protects OTA-mediated TNF-alpha release from perfused rat livers and
      isolated rat Kupffer cells.
AB  - We studied the inhibitory effect of silibinin on ochratoxin A (OTA) and LPS
      mediated tumor necrosis factor alpha (TNF-alpha) release and the leakage of
      cytotoxic markers glutamate dehydrogenase (GLDH) and lactate dehydrogenase (LDH),
      from isolated blood-free perfused rat livers, and from isolated pure rat Kupffer
      cells. In the recirculation perfusion model at the end point 90 min, 2.5
      micromol/L OTA released 2600 pg/mL TNF-alpha without effects on liver vitality.
      LPS at 0.1 microg/mL induced 3000 pg TNF-alpha/mL with slight leakage of GLDH and
      LDH. Under similar experimental conditions, the addition of silibinin 10 min
      prior to OTA and LPS showed dose-dependent protection against OTA or LPS-induced
      hepatic TNF-alpha release. High-dose of silibinin (12.5 microg/mL) also
      completely restored GLDH and LDH levels in the perfusate. Pretreatment of
      isolated Kupffer cells with 0.02, 0.1, 0.5, 2.5, and 12.5 microg silibinin/mL 30
      min prior to OTA reduced OTA-induced TNF-alpha levels to 90, 70, 25, 25, and 25%
      at 4 h, respectively, and abrogated any TNF-alpha release at 24 h. Similarly, in
      the presence of silibinin LPS-induced TNF-alpha levels decreased at 4 h to 71,
      57, 18, 22, and 18%, respectively. However, after 24 h of LPS exposition the
      protection by silibinin vanished and TNF-alpha partially recurred into the
      incubation medium under LPS. In summary, silibinin had hepatoprotective effects
      against OTA- or LPS-mediated TNF-alpha release and also reduced the cytotoxicity
      of both toxins. Isolated Kupffer cells were even more sensitive to the protective
      effect than perfused livers and responded to very low concentrations of silibinin
      with a strong inhibition of toxins-mediated TNF-alpha release.

PMID- 19156714
TI  - Structure-antioxidant relationship of flavonoids from fermented rooibos.
AB  - Rooibos tea (Aspalathus linearis) contains different bioactive phenolic compounds
      such as dihydrochalcones, flavonols, flavanones, flavones, and flavanols.
      Flavonoids isolated from rooibos were subjected to different in vitro assays:
      Trolox equivalent antioxidant activity, LDL oxidation and Fremy's salt assays to
      determine the total antioxidant activity (TAA). Assay results were compared, and
      the structure-antioxidant relationship was investigated. A decoupled LDL
      oxidation test was established with the objective of having an assay adapted more
      to an in vivo situation. The different in vitro methods were coupled offline to
      HPLC-DAD. Results from these coupled offline methods were compared to the TAA to
      assess the usefulness of the coupling setup.

PMID- 19156715
TI  - Alcohol use and prostate cancer: a meta-analysis.
AB  - Past reviews have concluded that there is no association between alcohol use and
      prostate cancer incidence. We performed a meta-analysis of existing
      epidemiological studies finding, in contrast, evidence to suggest that prostate
      incidence is positively linearly associated with heavier alcohol use. This
      finding was largely due to the contribution of population case-control studies
      and those measuring men recruited before age 60. No relationship between alcohol
      consumption and prostate cancer was found for cohort and hospital case-control
      studies. Analyses of design effects modestly suggests that population case
      control studies were probably better suited to identify potential alcohol
      prostate cancer relationships due to the close temporal proximity of the
      measurement of level of alcohol consumption to diagnosis. Future efforts should
      be made to exclude all ill subjects from control groups/baseline samples in
      addition to accounting for changes in consumption with advancing age and the
      onset of illness. The alcohol-prostate cancer association remained significant
      despite controlling for the degree to which studies endeavored to eliminate false
      negatives from their control groups.

PMID- 19156716
TI  - Environmental and seasonal influences on red raspberry anthocyanin antioxidant
      contents and identification of quantitative traits loci (QTL).
AB  - Consumption of raspberries promotes human health through intake of
      pharmaceutically active antioxidants, including cyanidin and pelargonidin
      anthocyanins; products of flavonoid metabolism and also pigments conferring
      colour to fruit. Raspberry anthocyanin contents could be enhanced for nutritional
      health and quality benefits utilising DNA polymorphisms in modern marker assisted
      breeding. The objective was to elucidate factors determining anthocyanin
      production in these fruits. HPLC quantified eight anthocyanin cyanidin and
      pelargonidin glycosides: -3-sophoroside, -3-glucoside, -3-rutinoside and -3
      glucosylrutinoside across two seasons and two environments in progeny from a
      cross between two Rubus subspecies, Rubus idaeus (cv. Glen Moy)xRubus strigosus
      (cv. Latham). Significant seasonal variation was detected across pigments less
      for different growing environments within seasons. Eight antioxidants mapped to
      the same chromosome region on linkage group (LG) 1, across both years and from
      fruits grown in field and under protected cultivation. Seven antioxidants also
      mapped to a region on LG 4 across years and for both growing sites. A chalcone
      synthase (PKS 1) gene sequence mapped to LG 7 but did not underlie the
      anthocyanin quantitative traits loci (QTL) identified. Other candidate genes
      including basic-helix-loop-helix (bHLH), NAM/CUC2-like protein and bZIP
      transcription factor underlying the mapped anthocyanins were identified.

PMID- 19156717
TI  - Human fetal colon cells and colon cancer cells respond differently to butyrate
      and PUFAs.
AB  - We verified the hypothesis suggesting modulation of the effects of sodium
      butyrate (NaBt) by omega-3 or omega-6 PUFAs. Comparing the response of human
      colon epithelial cell lines of fetal (FHC) and adenocarcinoma (HT-29, HCT-116)
      origin, we detected significant differences in proliferation, differentiation and
      apoptotic response to the treatment of NaBt, arachidonic or docosahexaenoic acids
      and their combination. While in FHC and HT-29 cells NaBt induced G0/G1 arrest,
      differentiation and low level of apoptosis, in HCT-116 cells G2/M arrest, no
      differentiation and high degree of apoptosis were detected. Moreover, in FHC
      cells significant potentiation of apoptosis accompanied by increased arrest in
      the cell cycle, cell detachment and decrease in differentiation were detected
      after combined treatment with NaBt and both PUFAs. Changes in cytokinetics
      induced by fatty acids were accompanied by membrane lipid unpacking, reactive
      oxygen species (ROS) production, and decrease in mitochondrial membrane potential
      (MMP). Detection of caspase-3 activation and dynamic modulation of Mcl-1 protein
      expression imply their possible role in both cell differentiation and apoptotic
      response. Our results support the concept of modulation of NaBt effects by PUFAs,
      especially of omega-3 type, in colonic cells in vitro with diverse impact in cell
      lines derived from normal or neoplastic epithelium.

PMID- 19156718
TI  - Elimination and metabolism of sesamol, a bioactive compound in sesame oil, in
      rats.
AB  - Sesamol, generally regarded as a main antioxidative component in sesame oil, is
      generated from sesamolin upon roasting of sesame seed or during bleaching process
      of sesame oil. This investigation studied the bioavailability and excretion of
      sesamol in Sprague-Dawley rats. After oral administration of sesamol (p.o. 100
      mg/kg) to SD rats, the changes in concentration of sesamol were determined in
      various excreta within 24 h period. Our results showed that sesamol conjugated
      metabolites were rapidly eliminated from urine and feces in 0-4 h. The majority
      of intact sesamol glucuronide was excreted in the urine. It is suggested that
      sesamol conjugated metabolites are primarily eliminated from the plasma via the
      kidney by active tubular secretion. LC-MS/MS analyses of rat excreta showed that
      sesamol can be converted to 2-methoxybenzene-1,4-diol and benzene-1,2,4-triol in
      vivo by rat.

PMID- 19156719
TI  - Association between functional FABP2 promoter haplotypes and body mass index:
      analyses of 8072 participants of the KORA cohort study.
AB  - Studies in relatively small cohorts provide preliminary evidence that functional
      fatty acid binding protein 2 (FABP2) promoter haplotypes are associated with type
      2 diabetes and BMI. Here, we studied the influence of the haplotypes on BMI by
      using 8072 male and female participants of the Kooperative Gesundheitsforschung
      in der Region Augsburg (KORA) cohort. By linear regression analysis, we found in
      males a reduction of -0.39 BMI units (95% CI: -0.73, -0.05, p = 0.024) in
      homozygous FABP2 promoter haplotype B carriers. Carriers of haplotype B showed a
      significant decrease in BMI of -0.19 BMI units (95% CI: -0.35, -0.02, p = 0.027).
      In accordance, a significant reduction in BMI of the minor haplotype carriers in
      the BMI point categories of 25-30 (BMI units: -0.10, 95% CI: -0.18, -0.01, p =
      0.03) and < 30 (BMI units: -0.37, 95% CI: -0.67, -0.07, p = 0.02) were found. In
      summary, the minor FABP2 promoter haplotype B contributes to a reduced BMI in
      men. This provides evidence that functional FABP2 contributes to multifactorialy
      regulated body weight.

PMID- 19156720
TI  - Hybridization of electron and hole states in semiconductor quantum-dot molecules.

PMID- 19156724
TI  - Fully in vitro selection of recombinant antibodies.
AB  - Antibodies are essential for the identification and characterization of proteins.
      In the current postgenomic era the need for highly specific antibodies has
      further increased not only for research applications but also because they
      represent one of the most promising therapeutic options, especially in the field
      of cancer treatment. One appealing approach for rapid and inexpensive antibody
      generation is the use of phage display. This technique allows for a fast and
      animal-free selection of highly functional alternatives to classical antibodies.
      However, one strong limitation of this recombinant approach has been the
      difficulty in producing and purifying antigens. These steps have to be adjusted
      for each new target, are time consuming and sometimes present an insurmountable
      obstacle. Here we report the development of new antibody selection approach where
      antigens are produced through in vitro translation and are used directly and
      without the need for purification. With this approach we were able to rapidly
      select recombinant antibodies directed against GFP and the mammalian protein
      tsg101, respectively. We believe that our method greatly facilitates antigen
      preparation and thus may broaden the use of the recombinant approach for antibody
      generation, especially since the technique could in the future be adapted to a
      high-throughput technology, thus further accelerating antibody selection.

PMID- 19156725
TI  - Biphasic mini-reactor for characterization of biocatalyst performance.
AB  - Biphasic reaction media are extending the scope of technical biocatalysis.
      Thorough investigation of the factors affecting catalyst performance under these
      conditions is of key importance for the successful implementation of catalytic
      processes. Here, we present a reactor setup suitable for comprehensive systematic
      characterization and optimization of biocatalyzed reactions in biphasic systems
      with distinct phases. It is distinguished by small volumes allowing reproducible
      experimentation with minimum amounts of solvent and catalyst. The interfacial
      area is kept constant and independent stirring of both phases is allowed in order
      to minimize superimposing effects. Evaporation of low-volatile organic solvents
      is prevented by use of airtight construction. The broad applicability of this
      mini-reactor is demonstrated with regard to determination of mass transfer,
      enzyme productivity, and enzyme stability in both batch and continuous mode.

PMID- 19156726
TI  - Quantitative analysis of intracellular sugar phosphates and sugar nucleotides in
      encapsulated streptococci using HPAEC-PAD.
AB  - Metabolomics is a powerful tool for the study of biological systems. Besides
      analytical techniques, cell harvest and extraction are critical steps, especially
      when studying encapsulated streptococci. We have compared four different
      harvesting techniques for biomass from liquid culture of the hyaluronic acid (HA)
      producing bacterium Streptococcus zooepidemicus. The best method for cell
      separation was quick (2 min) centrifugation, which allowed efficient medium
      removal and enabled quantification of the broadest range of sugar metabolites.
      Unlike observations for other microbes, changes in metabolite pools due to a
      delay of extraction by the centrifugation were not observed, so metabolite levels
      accurately reflected the metabolome at the point of cell harvest. A hypothesis is
      that the capsule itself isolates the cells from the surroundings and still
      supports it with nutrients during the harvest. Quantification of sugar phosphates
      and nucleotide sugars was performed using high-performance anion exchange
      chromatography combined with pulsed amperometric detection, achieving limits of
      quantification of 2.5 pmol for sugar phosphates and 5 pmol on column for
      nucleotide sugars. Intracellular pool sizes for intermediates of the HA pathway
      under production conditions ranged from 0.2 to 0.5 micromol/g cell dry weight.

PMID- 19156728
TI  - Expression system of CotA-laccase for directed evolution and high-throughput
      screenings for the oxidation of high-redox potential dyes.
AB  - Laccases are useful biocatalysts for many diverse biotechnological applications.
      In this study we have established efficient and reliable expression systems and
      high-throughput screenings for the recombinant CotA-laccase from Bacillus
      subtilis. The expression levels of cotA-laccase were compared in five different
      Escherichia coli host strains growing in 96-well microtiter plates under
      different culture conditions. Lower coefficients of variance (around 15%) were
      achieved using crude cell lysates of BL21 and KRX host strains growing under
      microaerobic conditions. Reproducible high-throughput screenings for the
      decolorization of high redox potential azo and anthraquinonic dyes were developed
      and optimized for identification of variants with increased redox potential. The
      enzymatic assays developed were tested for the screening of one mutant library
      from CotA-laccase created by error-prone PCR.

PMID- 19156729
TI  - Peptides: isolation, production, and use in India.

PMID- 19156730
TI  - Adsorption of peroxidase on Celite 545 directly from ammonium sulfate
      fractionated white radish (Raphanus sativus) proteins.
AB  - This paper demonstrates the direct immobilization of peroxidase from ammonium
      sulfate fractionated white radish proteins on an inorganic support, Celite 545.
      The adsorbed peroxidase was crosslinked by using glutaraldehyde. The activity
      yield for white radish peroxidase was adsorbed on Celite 545 was 70% and this
      activity was decreased and remained 60% of the initial activity after
      crosslinking by glutaraldehyde. The pH and temperature-optima for both soluble
      and immobilized peroxidase was at pH 5.5 and 40 degrees C. Immobilized peroxidase
      retained higher stability against heat and water-miscible organic solvents. In
      the presence of 5.0 mM mercuric chloride, immobilized white radish peroxidase
      retained 41% of its initial activity while the free enzyme lost 93% activity.
      Soluble enzyme lost 61% of its initial activity while immobilized peroxidase
      retained 86% of the original activity when exposed to 0.02 mM sodium azide for 1
      h. The K(m) values were 0.056 and 0.07 mM for free and immobilized enzyme,
      respectively. Immobilized white radish peroxidase exhibited lower V(max) as
      compared to the soluble enzyme. Immobilized peroxidase preparation showed better
      storage stability as compared to its soluble counterpart.

PMID- 19156732
TI  - Site-specific modification of the bovine genome using Cre recombinase-mediated
      gene targeting.
AB  - Cre recombinase (Cre)-mediated targeted insertion of a transgene is a powerful
      technique that can be used to tailor genomes. When combined with somatic cell
      nuclear transfer it could offer an efficient way to generate transgenic livestock
      with site-specific genetic modifications that are free of antibiotic selection
      markers. We have engineered primary bovine fibroblasts to contain a chromosomal
      acceptor site with incompatible loxP/lox2272 sites for Cre-mediated cassette
      exchange and show for the first time that Cre-mediated targeting can be applied
      in these acceptor cells. Molecular characterization of the resulting cell clones
      revealed Cre-mediated transgene insertion efficiencies of up to 98% when
      antibiotic selection was used to identify transgene containing cell clones. Most
      clonal lines also contained random insertions of the targeting and Cre expression
      plasmids with only about 10% of the clones being exclusively modified by the
      intended targeted insertion. This targeting efficiency was sufficient to enable
      the isolation of correctly targeted clones without the help of antibiotic
      selection. Therefore, this recombinase-mediated insertion strategy has the
      potential to produce transgenic cattle from antibiotic selection marker-free
      somatic cells with transgenes inserted into proven genomic loci ensuring reliable
      expression levels.

PMID- 19156734
TI  - Production of random DNA oligomers for scalable DNA computing.
AB  - While remarkably complex networks of connected DNA molecules can form from a
      relatively small number of distinct oligomer strands, a large computational space
      created by DNA reactions would ultimately require the use of many distinct DNA
      strands. The automatic synthesis of this many distinct strands is economically
      prohibitive. We present here a new approach to producing distinct DNA oligomers
      based on the polymerase chain reaction (PCR) amplification of a few random
      template sequences. As an example, we designed a DNA template sequence consisting
      of a 50-mer random DNA segment flanked by two 20-mer invariant primer sequences.
      Amplification of a dilute sample containing about 30 different template molecules
      allows us to obtain around 10(11) copies of these molecules and their
      complements. We demonstrate the use of these amplicons to implement some of the
      vector operations that will be required in a DNA implementation of an analog
      neural network.

PMID- 19156736
TI  - Transient protein expression in three Pisum sativum (green pea) varieties.
AB  - The expression of proteins in plants both transiently and via permanently
      transformed lines has been demonstrated by a number of groups. Transient plant
      expression systems, due to high expression levels and speed of production, show
      greater promise for the manufacturing of biopharmaceuticals when compared to
      permanent transformants. Expression vectors based on a tobacco mosaic virus (TMV)
      are the most commonly utilized and the primary plant used, Nicotiana benthamiana,
      has demonstrated the ability to express a wide range of proteins at levels
      amenable to purification. N. benthamiana has two limitations for its use; one is
      its relatively slow growth, and the other is its low biomass. To address these
      limitations we screened a number of legumes for transient protein expression.
      Using the alfalfa mosaic virus (AMV) and the cucumber mosaic virus (CMV) vectors,
      delivered via Agrobacterium, we were able to identify three Pisum sativum
      varieties that demonstrated protein expression transiently. Expression levels of
      420 +/- 26.24 mg GFP/kgFW in the green pea variety speckled pea were achieved. We
      were also able to express three therapeutic proteins indicating promise for this
      system in the production of biopharmaceuticals.

PMID- 19156737
TI  - Rapid prototyping of scaphoid and lunate bones.
AB  - In this study, a novel rapid prototyping technology was used to fabricate
      scaphoid and lunate bone prostheses, two carpal bones that are prone to avascular
      necrosis. Carpal prostheses were fabricated with an Envisiontec Perfactory SXGA
      stereolithography system using Envisiontec eShell 200 photocurable polymer.
      Fabrication was guided using 3-D models, which were generated using Mimics
      software (Materialise NV, Leuven, Belgium) from patient computer tomography data.
      The prostheses were fabricated in a layer-by-layer manner; approximately 50
      microm thick layers were observed in the prostheses. Hardness and Young's modulus
      values of polymerized eShell 200 material were 93.8 +/- 7.25 MPa and 3050 +/- 90
      MPa, respectively. The minimum compressive force required for fracture was 1360 N
      for the scaphoid prosthesis and 1248 N for the lunate prosthesis. Polymerized
      Envisiontec eShell material exhibited high human neonatal epidermal keratinocyte
      cell viability rate in an MTT assay. The results of this study indicate that
      small bone prostheses fabricated by stereolithography using eShell 200 polymer
      may have suitable geometry, mechanical properties, and cytocompatibility
      properties for in vivo use.

PMID- 19156743
TI  - Meeting report: the 13th International Biotechnology Symposium and Exhibition in
      Dalian, China.

PMID- 19156745
TI  - Electrospray-ionization mass spectrometry as a tool for fast screening of protein
      structural properties.
AB  - Since the early 1990s, electrospray-ionization mass spectrometry (ESI-MS) has
      encountered growing interest as a complementary tool to established biochemical
      and biophysical methods for investigating protein structure and conformation.
      Nowadays, applications of ESI-MS to protein investigation span from the area of
      analytical biochemistry to that of structural biology. This review focuses on
      applications of this technique to the analysis of protein conformational
      properties and molecular interactions, underscoring their possible relevance for
      molecular biotechnology, although representing a still very young field. An
      introductive section presents the major issues related to theoretical and
      technical aspects of ESI-MS under non-denaturing conditions. Examples from our
      work and from the literature illustrate which kind of information can be obtained
      concerning key issues in biotechnology such as stability and aggregation of
      proteins under both near-native and challenging conditions, and interactions with
      other proteins, ligands and cofactors.

PMID- 19156746
TI  - MicroRNA expression profiling in bone marrow: implications in hematological
      malignancies.
AB  - MicroRNA (miRNA) have been recently attributed a crucial role in the control of
      gene expression in numerous physiological and pathological processes including
      growth, differentiation and even oncogenesis. Besides detailed mechanistic
      studies on their generation and function, there has been a great deal of interest
      in the study of miRNA as surrogate markers of disease. Numerous studies have
      attempted to define miRNA profiles as predictors of disease outcome, or for the
      classification/diagnosis of different pathologies. In the present review, we
      summarize the main studies describing the involvement of miRNA in bone marrow
      (BM) diseases and in normal BM function during hematopoiesis.

PMID- 19156748
TI  - Singapore R&D and globetrotting.

PMID- 19156749
TI  - Synergistic virus inactivation effects of arginine.

PMID- 19156750
TI  - Increased myocardial wall thickening as index of viability assessment: a
      preliminary report on delayed contrast MRI.
AB  - PURPOSE: Regional wall thickening measurement by delayed contrast MRI may assess
      myocardial viability and functional recovery of ischemic cardiomyopathy.
      MATERIALS AND METHODS: Delayed contrast MRI data was used in 40 patients with
      significant coronary artery disease and severe left ventricular dysfunction.
      Regional wall thickening on follow-up MRI served as an index of functional
      recovery in patients receiving revascularization. For comparison, myocardial
      viability was assessed by MRI and 201Tl SPECT in 10 patients using a 17-segment
      method. RESULTS: On 480 segments, MRI hyperintensities showed positive
      correlation with 201Tl reduction (r = 0.71, p < 0.0001) in the inferior wall and
      apex. Delayed MRI detected myocardial viability better than 201Tl SPECT. Delayed
      contrast-enhanced MRI showed diagnostic accuracy 65%, sensitivity 95%,
      specificity 25%, positive predictive value 65% and negative predictive value 75%,
      whereas 201Tl SPECT showed diagnostic accuracy 54%, sensitivity 72%, specificity
      25%, positive predictive value 52% and negative predictive value 54%. Areas under
      the ROC curves by MRI and 201Tl SPECT were 0.59 +/- 0.04, 0.52 +/- 0.05,
      respectively (p = 0.07). The viability concordance was 80% between 201Tl SPECT
      and MRI. CONCLUSION: Delayed contrast-enhanced MRI may detect the inferior wall
      thickening and apex as an index of viable myocardium better than 201Tl SPECT.
      Myocardial viability may predict functional recovery after revascularization in
      ischemic cardiomyopathy.

PMID- 19156751
TI  - Profile, comorbidity and impact of insomnia in the Ibadan study of ageing.
AB  - OBJECTIVE: To provide information on the profile, comorbidity and impact of
      insomnia among an understudied group of elderly Africans. METHOD: Using the WHO
      Composite International Diagnostic Interview (CIDI), the 12-month prevalence of
      three forms of insomnia was assessed in face-to-face interviews conducted with a
      regionally-representative sample of elderly Nigerians, aged 65 years and over (n
      = 2152). The association of insomnia with quality of life, rated with the WHO
      Quality of Life instrument, was analyzed controlling for comorbid chronic pain,
      chronic medical conditions and DSM-IV major depressive disorder. RESULTS: At
      least one insomnia problem was reported by 30.72%. Insomnia was more frequent
      among females, persons aged 70 years and over, and those who were unmarried.
      Insomnia was comorbid with major depressive disorder (OR = 3.9, 95% CI 2.5-6.1),
      chronic pain (OR = 4.3, 95% CI 3.2-6.1; particularly arthritis and spinal pain),
      and chronic medical conditions (OR = 2.1, 95% CI 1.8-2.5, particularly heart
      disease, high blood pressure or asthma). Persons with insomnia were more likely
      to report having had a fall in the previous year (OR = 1.4, 95% CI 1.0-1.8) and,
      among those with fall, injury was more commonly reported by those with insomnia.
      Every form of insomnia was associated with decrement in quality of life. After
      controlling for comorbid mental and physical conditions, the beta coefficients
      ranged between -17.9 and -20.0. CONCLUSION: Insomnia was highly comorbid with
      chronic physical conditions and with depression. These comorbid conditions partly
      but do not entirely account for the considerable decrement in quality of life
      associated with insomnia.

PMID- 19156752
TI  - Utilisation of cardiovascular medicines in Republic of Srpska, Bosnia and
      Herzegovina, 5 years study.
AB  - PURPOSE: The objective of this study was to analyse cardiovascular medicines
      utilisation patterns in Republic of Srpska (Bosnia and Herzegovina) over the 2002
      2006 period. METHODS: A retrospective study was taken to analyse utilisation
      medicines reimbursed by the Health Insurance Fund (HIF), with a focus on
      cardiovascular medicines utilisation. ATC/DDD methodology was used to monitor
      utilisation of medicines. Drug utilisation 90% (DU90%) method was used to
      determine the prescribing quality of cardiovascular medicines. RESULTS:
      Utilisation of cardiovascular medicines accounted for more than one half of the
      total medicines utilisation, with an increasing trend. Most prescribed were
      antihypertensive medicines i.e. ACE inhibitors, both plain and in combination
      with thiazide diuretics, and calcium channel blockers (CCB). Utilisation of beta
      blockers and thiazide diuretics remains rather low despite an overall increase in
      utilisation. Re-introduction of statins in 2004 instantly led to high
      utilisation. The number of cardiovascular medicines within DU90% segment varies
      from 8 in 2002 to 12 in 2006. CONCLUSIONS: This study showed a constant increase
      in total medicines utilisation with the cardiovascular medicines as the most
      prescribed. DU90% is shown as a simple method for assessing general quality of
      medicines prescribing, which indicated that better adherence to the guidelines is
      needed in order to practice a more rational use of medicines and a cost-efficient
      use of all resources. More stratified routinely performed analyses are also
      needed.

PMID- 19156753
TI  - Molecular mechanisms of cervical carcinogenesis by high-risk human
      papillomaviruses: novel functions of E6 and E7 oncoproteins.
AB  - Over the last two decades, since the initial discovery of human papillomavirus
      (HPV) type 16 and 18 DNAs in cervical cancers by Dr. Harald zur Hausen (winner of
      the Nobel Prize in Physiology or Medicine, 2008), the HPVs have been well
      characterised as causative agents for cervical cancer. Viral DNA from a specific
      group of HPVs can be detected in at least 90% of all cervical cancers and two
      viral genes, E6 and E7, are invariably expressed in HPV-positive cervical cancer
      cells. Their gene products are known to inactivate the major tumour suppressors,
      p53 and retinoblastoma protein (pRB), respectively. In addition, one function of
      E6 is to activate telomerase, and E6 and E7 cooperate to effectively immortalise
      human primary epithelial cells. Though expression of E6 and E7 is itself not
      sufficient for cancer development, it seems to be either directly or indirectly
      involved in every stage of multi-step carcinogenesis. Epidemiological and
      biological studies suggest the potential efficacy of prophylactic vaccines to
      prevent genital HPV infection as an anti-cancer strategy. However, given the
      widespread nature of HPV infection and unresolved issues about the duration and
      type specificity of the currently available HPV vaccines, it is crucial that
      molecular details of the natural history of HPV infection as well as the
      biological activities of the viral oncoproteins be elucidated in order to provide
      the basis for development of new therapeutic strategies against HPV-associated
      malignancies. This review highlights novel functions of E6 and E7 as well as the
      molecular mechanisms of HPV-induced carcinogenesis.

PMID- 19156754
TI  - Plasmapheresis therapy for rare but potentially fatal reaction to rituximab.
AB  - Rituximab (Rituxan), a genetically engineered chimeric murine and human IgG1
      monoclonal antibody directed against CD20 antigen, is an emerging drug used for a
      wide spectrum of disease processes and found to be relatively safe. We report a
      near-fatal reaction to rituximab, which started 30 min after infusion and
      worsened over 24 to 48 h, resulting in hemodynamic and respiratory compromise
      that necessitated both intubation and high-dose vasopressors. Subsequent
      treatment with plasmapheresis helped stabilize and improve the patient's clinical
      condition, and the patient was discharged home on hospital day 5. There is no
      specific treatment for these severe and sometimes fatal reactions except
      supportive care with plasmapheresis. With the increased use of rituximab therapy
      in the medical management of numerous diseases, those in the medical community
      need to be cognizant of the rare fatal or near-fatal infusion reaction and the
      benefit that may accrue from plasmapheresis therapy.

PMID- 19156755
TI  - ADAMTS13 activity levels in patients with human immunodeficiency virus-associated
      thrombotic microangiopathy and profound CD4 deficiency.
AB  - BACKGROUND: Thrombotic microangiopathy (TMA) encompasses a number of disorders
      with hemolytic anemia and thrombocytopenia, including thrombotic thrombocytopenic
      purpura (TTP). A deficiency in ADAMTS13 enzyme levels, along with an inhibitory
      antibody, is found in most patients with idiopathic TTP. Patients with human
      immunodeficiency virus (HIV) infection can have a TTP-like illness; however, it
      appears to have a different etiology. METHODS: A retrospective review of patients
      who had an ADAMTS13 activity level performed from 2005 through 2007 was
      completed. Patients with a diagnosis of HIV infection with TMA were investigated.
      RESULTS: Two patients were identified. Case 1: a 47-year-old man with HIV
      infection and a CD4 count <10/microL presented with altered mental status,
      pneumonia, acute renal failure, thrombocytopenia, and anemia. The ADAMTS13 level
      was 71%. He was treated with plasma infusion. Two days after admission, he
      expired because of respiratory distress syndrome and metabolic lactic acidosis.
      Case 2: a 39-year-old man with HIV infection and a CD4 count of 9/microL
      presented with chest pain, acute renal failure, thrombocytopenia, and anemia. The
      ADAMTS13 level was 65%. He received multiple units of fresh frozen plasma without
      significant improvement in his platelet count. Six days after admission, the
      patient began highly active antiretroviral therapy, which resulted in a rapid
      increase in his platelet count. CONCLUSIONS: HIV-associated TMA is postulated to
      have a different pathophysiology than idiopathic TTP. This study supports that
      assumption because both patients exhibited many of the classic findings of TTP
      but did not have a deficiency of ADAMTS13.

PMID- 19156756
TI  - Multiple myeloma patients receiving large volume leukapheresis efficiently yield
      enough CD34+ cells to allow double transplants.
AB  - Current protocols for myeloma patients require more than one autologous
      transplant. We performed a retrospective study to determine the cost
      effectiveness of large volume leukapheresis (LVL) compared with standard volume
      leukapheresis (SVL) collection when two transplants are required. We evaluated 87
      patients who underwent a cumulative total of 260 LVL and SVL collections. The
      median product volume per collection was 356 ml for LVL, and this was
      significantly higher than the median product volume per collection for SVL
      (median 149.5 ml, P < 0.001). The median total CD34+ cell yield/kg was 6.4 x
      10(6) for LVL and 5.2 x 10(6) for SVL. This difference was statistically
      significant (P = 0.005). Because the target CD34+ cell dose for a single
      transplant was 3 x 10(6)/kg at our institution, overall the LVL yields enough
      CD34+ cells that could allow for two transplants. Therefore, more patients in the
      LVL group were able to undergo a potential second transplant. Because of the
      reserved cells for a second transplant, LVL patients received significantly less
      CD34+ cell/kg per transplant than the patients in SVL group (P = <0.001). As a
      result, LVL group had statistically significant but clinically insignificant
      delay in neutrophil (P = <0.001) and platelet (P = 0.02) engraftments.
      Additionally, using LVL instead of SVL to collect >or=6 x 10(6)/kg CD34+ cells
      may potentially save $7,497 per patient. We therefore conclude that LVL is the
      method of choice for collection of multiple myeloma patients when two transplants
      are anticipated.

PMID- 19156757
TI  - Prognosis is important in decisionmaking in Dutch nursing home patients with
      dementia and pneumonia.
AB  - OBJECTIVE: To explore how physicians treating nursing home residents with
      dementia and pneumonia in the Netherlands consider prognosis in their treatment
      decision. METHODS: Survey study with data collected between July 2006 and March
      2008. Physicians (n = 69) from 54 nursing homes in the Netherlands completed a
      questionnaire on symptoms, treatment, and prognosis for their next dementia
      patient newly diagnosed with pneumonia. They were also asked a general question
      regarding withholding antibiotic treatment and prognosis. Outcome was assessed at
      least two months afterwards. Two-week mortality risk if treated with antibiotics
      was calculated with a validated prognostic score. RESULTS: The patients not
      treated with antibiotics had high (92%) actual 2-week mortality while only 12% of
      patients treated with antibiotics died. Physicians believed that mortality risk
      was high in the untreated group and would have been only slightly lower if
      treated with antibiotics (mean estimated risk 73%), which was higher than
      predicted from the risk score (42%). In general, three-quarters of physicians
      considered withholding antibiotics appropriate for mortality risks between 75%
      and 90%. CONCLUSIONS: Prognosis is an important consideration when Dutch nursing
      home physicians make antibiotic treatment decisions for patients with dementia
      and pneumonia. This suggests they prefer not to treat with antibiotics when to do
      so is probably futile. Physicians in other countries may hold different views on
      futility, which should be addressed in larger, cross-national comparative
      studies.

PMID- 19156758
TI  - Screening and confirmatory methods for the analysis of macrocyclic lactone
      mycotoxins by CE with amperometric detection.
AB  - A simple analytical scheme for the screening and quantification of zearalenone
      and its metabolites, alpha-zearalenol and beta-zearalenol, is reported. Extracts
      from maize flour samples were collected by supercritical fluid extraction and
      afterwards, they were analyzed by CE with amperometric detection. This scheme
      allowed a rapid and reliable identification of contaminated flour samples
      according to the reference value established for zearalenone by directive
      2005/38/EC (200 microg/kg). The sample screening method was carried out by CZE
      using 25 mM borate separation buffer at pH 9.2 and 25.0 kV as separation voltage,
      monitoring the amperometric signal at +700 mV with a carbon paste electrode. In
      this way, total amount of mycotoxins was determined and samples were processed in
      4 min with a detection limit of 12 microg/L, enough to discriminate between
      positive (more than 200 microg/L total mycotoxins) and negative samples (less
      than 200 microg/L total mycotoxins). Positive samples were then subjected to CZE
      separation and quantification of each analyte was done with 50 mM borate running
      buffer modified with 30% methanol at pH 9.7 and 17.5 kV as separation voltage.
      Under these conditions, separation was achieved in 15 min with detection limits
      from 20 to 35 microg/L for each analyte.

PMID- 19156759
TI  - Integrated microdevice for preconcentration and separation of a wide variety of
      compounds by electrochromatography.
AB  - An integrated microdevice was developed to couple on-chip SPE to separation by
      channel electrochromatography. An acrylate-based monolith was synthesized within
      a glass microdevice by photoinitiated polymerization. It was used for both
      separation and preconcentration by direct injection on the head of the stationary
      phase or by confining the preconcentration step in a given zone of the stationary
      phase. The composition of the polymerization mixture was chosen to achieve a
      monolithic material containing both hydrophobic and charged moieties to ensure an
      electroosmotic flow for separation. As a consequence the extraction procedure
      occurs via hydrophobic and ionic interactions. Neutral, ionizable and charged
      compounds were successfully preconcentrated and separated within the microdevice
      through electrochromatographic mechanisms, highlighting the versatility of this
      device. The performance of the integrated microdevice was demonstrated with the
      preconcentration and separation of a mixture of PAHs for which a signal
      enhancement factor (SEF) of 270 was achieved within 120 s of preconcentration. In
      the case of charged and ionizable compounds, according to the electrolyte
      composition, contributions of both reverse-phase and ion-exchange mechanisms were
      used to perform effective electrochromatographic preconcentration. A SEF of 250
      was obtained for the model-charged compound within 20 s of preconcentration.
      Finally, the potentials of on-chip preconcentrate and separate both neutral and
      ionized compounds have been demonstrated using a mixture of model compounds.

PMID- 19156760
TI  - Neurotrophin 3/TrkC-regulated proteins in the human medulloblastoma cell line
      DAOY.
AB  - Medulloblastoma (MB) is the most common malignant childhood brain tumor and high
      neurotrophin (NP) receptor TrkC mRNA expression was identified as a powerful
      independent predictor of favorable survival outcome. In order to determine
      downstream effector proteins of TrkC signaling, the MB cell line DAOY was stably
      transfected with a vector containing the full-length TrkC cDNA sequence or an
      empty vector control. A proteomic approach was used to search for expressional
      changes by two mass spectrometric methods and immunoblotting for validation of
      significant results. Multiple time points for up to 48 h following NP-3-induced
      TrkC receptor activation were chosen. Thirteen proteins from several pathways
      (nucleoside diphosphate kinase A, stathmin, valosin-containing protein, annexin
      A1, dihydropyrimidinase-related protein-3, DJ-1 protein, glutathione S
      transferase P, lamin A/C, fascin, cofilin, vimentin, vinculin, and moesin) were
      differentially expressed and most have been shown to play a role in
      differentiation, migration, invasion, proliferation, apoptosis, drug resistance,
      or oncogenesis. Knowledge on effectors of TrkC signaling may represent a first
      useful step for the identification of marker candidates or reflecting probable
      pharmacological targets for specific treatment of MB.

PMID- 19156761
TI  - CE-based detection of methicillin-resistant Staphylococcus aureus.
AB  - Rapid and sensitive detection of methicillin-resistant Staphylococcus aureus is
      crucial for effective treatment and control of clinical infections caused by this
      bacterium. The goal of this study is to develop a CE-based detection method for
      multiplexed identification of a femA sequence specific for S. aureus and a unique
      mecA sequence encoding methicillin resistance. Blood samples spiked with known
      concentrations of bacteria were used for testing. Crude cell lysates were
      prepared by treating the spiked blood samples with DNazol Direct reagent and used
      as the template for isothermal amplification of mecA and femA genes. The
      amplified gene products then underwent a cycling probe reaction (CPR)-based assay
      to generate a short fluorophore-labeled oligonucleotide for detection in a CZE
      LIF system. The assay enables a gene-specific fluorophore-labeled DNA-RNA-DNA
      chimeric probe to hybridize with complementary target in the presence of RNase H
      enzyme. The RNase H enzyme specifically cleaves probe RNA residues of the duplex,
      releasing a fluorophore fragment for detection and the target for recycling and
      hybridization with another chimeric probe. Intact and cleaved probe fragments
      were separated and detected using a CZE-LIF system. The limit of detection for
      isothermal amplification and CPR-CZE-LIF was approximately 10(4) colony-forming
      units of bacteria/mL of blood. This method accurately detects methicillin
      resistant S. aureus within 3 h.

PMID- 19156762
TI  - Selective enrichment of albumin in biological samples by CE using segmental
      filling with sodium octyl sulfate in the background electrolyte.
AB  - This paper shows that in CE, the peak efficiency and effective electrophoretic
      mobility of HSA and BSA were significantly enhanced by using a short plug (8 nL)
      of 1% w/w sodium octyl sulfate (SOS) and 1% w/v dextran sulfate as the additive.
      However, under identical conditions, other proteins did not exhibit the same
      phenomena. When the concentration of SOS was increased to 1.0% w/w SOS, a broad
      peak that corresponded to HSA transformed to a sharp peak. When the SOS
      concentration was more than 3.0% w/w, there was no shift in the effective
      electrophoretic mobility of HSA (10 microM), indicating that the binding of SOS
      to HSA is saturated. Through the specific interaction between SOS and HSA, the
      selective sweeping of HSA was accomplished using a short plug (24 nL) of 1% w/w
      SOS, followed by the injection of 190 nL of the sample. The excellent peak
      efficiency was still obtained for HSA and BSA upon the injection of a large
      volume sample. As a result, the LOD for HSA (S/N=3) was 0.1 nM. In contrast to
      the normal injection without the SOS plug, approximately, a 4000-fold increase in
      the sensitivity of HSA was obtained by using the sweeping method. The proposed
      method has been successfully applied for the quantification of HSA in urine and
      erythrocytes as well as the quantification of BSA in milk.

PMID- 19156763
TI  - Simulation of desalting that occurs during isoelectric trapping separations.
AB  - Simul 5, the simulation program based on the 1-D model of electrophoresis has
      been extended to simulate isoelectric trapping (IET) separations that take place
      in recirculating multicompartmental electrolyzers (MCEs). In the extended Simul
      5, the simulated separation space between the anode and cathode can be divided
      into multiple segments to represent the anode compartment, separation
      compartment(s) and the cathode compartment. The compartments may have identical
      or different cross sections. A new algorithm simulates convective mixing that
      occurs in the recirculating MCEs where the distances between the buffering
      membranes are short and the velocities of tangential flows through the
      compartments, orthogonal to the electric field, are high. The intensity of
      simulated mixing can be independently controlled in each compartment. pH
      transients that were reported to occur during the desalting step in IET
      separations were simulated with the extended Simul 5 program: the main features
      of the experimental results were reproduced by the simulations. The simulations
      shed light on the possible causes of uneven anion and cation removal rates, pH
      transients and the transient invasion of the separation compartment by components
      of the electrode solutions that might occur during the desalting step.

PMID- 19156764
TI  - Two-dimensional phosphate-affinity gel electrophoresis for the analysis of
      phosphoprotein isotypes.
AB  - Herein, we describe three kinds of 2-DE using phosphate-affinity PAGE for the
      analysis of phosphoprotein isotypes. The first dimension is a urea-PAGE,
      IEF/NEPHGE, or SDS-PAGE, which are widely used. The second dimension is a
      phosphate-affinity SDS-PAGE using a phosphate-binding tag molecule, Phos-tag
      (Mn(2+)-Phos-tag SDS-PAGE). The first 2-D procedure coupling urea-PAGE and Mn(2+)
      Phos-tag SDS-PAGE was applied to the separation of beta-casein phosphoisotypes. A
      typical protein sample containing multiple phosphoisotypes from beta-casein (with
      five phosphorylation sites) was prepared by partial dephosphorylation with
      alkaline phosphatase. The second procedure coupling IEF/NEPHGE and Mn(2+)-Phos
      tag SDS-PAGE was applied to the separations of phosphoisotypes of caseins and in
      vitro kinase reaction products of Tau. The third procedure coupling normal SDS
      PAGE and Mn(2+)-Phos-tag SDS-PAGE was applied to the separation of A431 cell
      lysates before and after stimulation with an epidermal growth factor. This
      procedure followed by immunoblotting with anti-mitogen-activated protein
      kinase(MAPK) and anti-Shc antibodies demonstrated the detection of
      phosphoisotypes in each protein isoform of MAPK1/2 (44 and 42 kDa) and Shc (66,
      52, and 46 kDa) after the stimulation. By these novel 2-D procedures, the
      separations of phosphoprotein isotypes should be improved relative to those by
      current gel electrophoresis methods, including 1-D Mn(2+)-Phos-tag SDS-PAGE.

PMID- 19156765
TI  - CEC with new monolithic stationary phase based on a fluorinated monomer,
      trifluoroethyl methacrylate.
AB  - A new, fluorinated monolithic stationary phase for CEC was first synthesized by a
      single-stage, thermally initiated copolymerization of a fluorinated monomer,
      2,2,2-trifluoroethyl methacrylate (TFEM) and ethylene dimethacrylate (EDMA) in
      the presence of a porogen mixture. In this preparation, 2-acrylamido-2-methyl-1
      propanesulfonic acid was used as the charge-bearing monomer. The porogen mixture
      was prepared by mixing isoamylalcohol and 1,4-butanediol. A clear increase in the
      electroosmotic mobility was observed with increasing pH. The electroosmotic
      mobility decreased with increasing ACN concentration. Poly(TFEM-co-EDMA) monolith
      prepared under optimized polymerization conditions was successfully used in the
      separation of alkylbenzenes and phenols by CEC. The best chromatographic
      separation for alkylbenzenes was performed with lower ACN concentrations (i.e.
      60% v/v) with respect to the common acrylic-based CEC monoliths. The theoretical
      plate numbers up to 220 000 plates/m were achieved in the reversed phase
      separation of phenols. Poly(TFEM-co-EDMA) monolith also allowed the simultaneous
      separation of aniline and benzoic acid derivatives by a single run and by using a
      lower ACN concentration in the mobile phase with respect to the similar
      electrochromatographic separations. A stable retention behaviour in reversed
      phase separation of alkylbenzenes was obtained with the poly(TFEM-co-EDMA)
      monolith.

PMID- 19156766
TI  - Application of Click-chemistry-based perphenylcarbamated beta-CD chiral
      stationary phase in CEC.
AB  - A novel chiral stationary phase (CSP) was prepared by anchoring mono-6-azido-6
      deoxyperphenylcarbamated beta-CD onto omega-alkynyl functionalized silica (5
      microm) via organic soluble Cu(I)-catalyzed Click chemistry. The obtained CSP was
      thereafter packed into fused-silica capillary (100 microm id) with an effective
      length of 9 cm and tested in aqueous CEC to separate a series of racemic aryl
      alcohols. High separation factors with good resolution were achieved using the
      current novel CSP. Some pharmaceutical compounds could also be well resolved on
      this newly derived CSP. The analytical results demonstrate that Click-chemistry
      based perphenylcarbamated CSP affords high stability in high electric field and
      depicts excellent enantioseparation in CEC. The effects of pH value, buffer
      concentration, applied voltage, concentration of organic modifier and analyte
      structure on the enantioseparation are also discussed.

PMID- 19156767
TI  - Development of an in-capillary derivatization method by CE for the determination
      of chiral amino acids in dietary supplements and wines.
AB  - A fast in-capillary derivatization method by CE with 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate was developed for the first time for the
      determination of amino acid enantiomers (arginine, lysine, and ornithine) in
      dietary supplements and wines. Because of the initial current problems due to the
      formation of precipitates into the capillary during the derivatization reaction,
      a washing step with an organic solvent as DMSO between injections was necessary.
      Different approaches were also investigated to enhance the sensitivity of
      detection. A derivatization procedure, where plugs of ACN, derivatizing agent (10
      mM 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate), and sample in borate (1:1
      v/v) were injected in tandem (2, 3, and 6 s, respectively, at 50 mbar), was
      selected because it enabled to obtain the most sensitive and reproducible
      results. Appropriate analytical characteristics (linearity, LOD and LOQ,
      precision, absence of matrix interferences, and accuracy) were obtained for this
      method. Finally, the optimized method was successfully applied to the
      determination of the enantiomers of arginine, lysine, and ornithine in food
      samples of different complexities (dietary supplements and wines).

PMID- 19156768
TI  - Influence of different proteomic protocols on degree of high-coverage
      identification of nonspecific lipid transfer protein 1 modified during malting.
AB  - Both top-down (combining protein separation with MS analysis of intact proteins)
      and bottom-up (MS analysis of digested proteins) proteomic approaches were used
      for detailed characterization of nonspecific lipid transfer protein from barley
      malt. The aim was obtaining high-coverage of the primary structure of the
      proteins and the determination of PTMs such as lipid adduction and glycation.
      Here we present an influence of 15 proteomic protocols (differing in applied
      separation technique, enzyme and digestion procedure) on the extent of the
      coverage of the protein primary structure. The most successful protocols were in
      gel digestion with trypsin of alkylated protein and in-solution digestions with
      trypsin or trypsin/chymotrypsin mixture of the nonalkylated protein. Totally,
      full sequence coverage based on the PMF and 85% sequence coverage based on the
      peptide fragmentation including PTMs was obtained.

PMID- 19156769
TI  - Separation and detection of isoquinoline alkaloids using MEEKC coupled with field
      amplified sample injection induced by ACN.
AB  - New methods based on MEEKC coupling with field-amplified sample injection (FASI)
      induced by ACN were proposed for five isoquinoline alkaloids (berberine,
      palmatine, jatrorrhizine, sinomenine and homoharringtonine) in no salt and high
      salt sample solution (HS). For the separation of five isoquinoline alkaloids, a
      running buffer composed of 18 mM sodium cholate, 2.4% v/v butan-1-ol, 0.6% v/v
      ethyl acetate, 10% v/v (or 30% v/v) methanol and 87.0% v/v (or 67% v/v) 5 mM
      Na2B4O7~10 mM NaH2PO4 buffer (pH 7.5) was developed. In order to improve the
      sensitivity, FASI induced by ACN was applied to increase the detection
      sensitivity. The detection limit was found to be as low as 0.0002 microg/mL in no
      salt sample solution and 0.062 microg/mL in HS. The method has been applied for
      the analysis of human urine spiked with analytes, and the assay results were
      proved to be satisfactory, and also the determination of berberine in urine
      sample after oral administration berberine.

PMID- 19156770
TI  - A rapid MEKC method for the simultaneous determination of creatinine, 1- and 3
      methylhistidine in human urine.
AB  - The present report describes the use of MEKC in the presence of 35 mM sodium
      tetraborate, pH 9.0, containing 60 mM SDS for the complete separation and
      identification of creatinine, 1-methylhistidine (1-MeH) and 3-MeH in human urine.
      Their simultaneous quantification in urine of healthy controls and subjects
      submitted to elective surgery to their lower limbs allowed to use 3-MeH as a
      reliable measure of skeletal protein breakdown. Simplicity, sensitivity and low
      running costs are the main advantages of this method that is suitable for the
      routine analysis in clinical laboratories of a large number of samples per day.

PMID- 19156771
TI  - 18-crown-6 as a class I organic modifier in MEKC.
AB  - The use of 18-crown-6 as a class I organic modifier for SDS MEKC is described.
      Two positional isomer series, one neutral (nitrotoluenes) and one anionic
      (nitrophenols), are used to demonstrate different effects of 18-crown-6 on
      analyte retention in SDS MEKC.

PMID- 19156772
TI  - Clinical improvement of a patient with severe Wilson's disease after a single
      session of therapeutic plasma exchange.
AB  - Here, we report a case of a 17-year old female with Wilson's disease presenting
      with progressive Coombs' negative hemolytic anemia and hepatic cirrhosis who was
      treated with one session of therapeutic plasma exchange (TPE) and clinically
      improved. In clinical situations where multiple sessions of TPE may not be
      possible, the use of a single session of TPE in conjunction with conventional
      therapy may be of benefit in preventing further clinical deterioration.

PMID- 19156773
TI  - Analysis of the clonal architecture of the human small intestinal epithelium
      establishes a common stem cell for all lineages and reveals a mechanism for the
      fixation and spread of mutations.
AB  - Little is known about the clonal structure or stem cell architecture of the human
      small intestinal crypt/villus unit, or how mutations spread and become fixed.
      Using mitochondrial DNA (mtDNA) mutations as a marker of clonal expansion of stem
      cell progeny, we aimed to provide answers to these questions. Enzyme
      histochemistry (for cytochrome c oxidase and succinate dehydrogenase) was
      performed on frozen sections of normal human duodenum. Laser-capture
      microdissected cells were taken from crypts/villi. The entire mitochondrial
      genome was amplified using a nested PCR protocol; sequencing identified mutations
      and immunohistochemistry demonstrated specific cell lineages. Cytochrome c
      oxidase-deficient small bowel crypts were observed within all sections: negative
      crypts contained the same clonal mutation and all differentiated epithelial
      lineages were present, indicating a common stem cell origin. Mixed crypts were
      also detected, confirming the existence of multiple stem cells. We observed
      crypts where Paneth cells were positive but the rest of the crypt was deficient.
      We have demonstrated patches of deficient crypts that shared a common mutation,
      suggesting that they have divided by fission. We have shown that all cells within
      a small intestinal crypt are derived from one common stem cell. Partially-mutated
      crypts revealed some novel features of Paneth cell biology, suggesting that
      either they are long-lived or a committed Paneth cell-specific long-lived
      progenitor was present. We have demonstrated that mutations are fixed in the
      small bowel by fission and this has important implications for adenoma
      development.

PMID- 19156774
TI  - Aberrant BRAF splicing as an alternative mechanism for oncogenic B-Raf activation
      in thyroid carcinoma.
AB  - Activating BRAF mutations have recently been reported in 28-83% of papillary
      thyroid carcinomas (PTCs). However, it is not known whether aberrant BRAF
      splicing occurs in thyroid carcinoma. To investigate aberrant BRAF splicing and
      its association with BRAF mutation in thyroid tumours, we studied aberrant BRAF
      splicing and BRAF mutation from 68 thyroid tumours. BRAF(V600E) mutation was
      detected in 20 of 43 PTCs and all three anaplastic thyroid carcinomas (ATCs).
      There is a higher frequency of BRAF mutation in PTC patients with stage III and
      IV tumours compared with stage I and II. Novel BRAF splicing variants were
      detected in 12 PTCs, three follicular variants of PTC (FVPTCs), and one ATC, as
      well as in two thyroid carcinoma cell lines, ARO and NPA. These variants did not
      have the N-terminal auto-inhibitory domain of wild-type B-Raf, resulting in an in
      frame truncated protein that contained only the C-terminal kinase domain and
      caused constitutive activation of B-Raf. These variants were significantly
      associated with advanced disease stage and BRAF(V600E) mutation (p < 0.001,
      Fisher exact test). Furthermore, expression of these variants in NIH3T3 and CHO
      cells could activate the MAP kinase signalling pathway, transform them in vitro,
      and induce tumours in nude mice. These data suggest that BRAF splicing variants
      may function as an alternative mechanism for oncogenic B-Raf activation.
      Combination of the BRAF(V600E) mutation and its splicing variants may contribute
      towards disease progression to poorly differentiated thyroid carcinoma.

PMID- 19156775
TI  - Development and validation of a novel protein extraction methodology for
      quantitation of protein expression in formalin-fixed paraffin-embedded tissues
      using western blotting.
AB  - The development of efficient formaldehyde cross-link reversal strategies will
      make the vast diagnostic tissue archives of pathology departments amenable to
      prospective and retrospective translational research, particularly in biomarker
      driven proteomic investigations. Heat-induced antigen retrieval strategies
      (HIARs) have achieved varying degrees of cross-link reversal, potentially
      enabling archival tissue usage for proteomic applications outside its current
      remit of immunohistochemistry (IHC). While most successes achieved so far have
      been based on retrieving tryptic peptide fragments using shot-gun proteomic
      approaches, attempts at extracting full-length, non-degraded, immunoreactive
      proteins from archival tissue have proved challenging. We have developed a novel
      heat-induced antigen retrieval strategy using SDS-containing Laemmli buffer for
      efficient intact protein recovery from formalin-fixed tissues for subsequent
      analysis by western blotting. Protocol optimization and comparison of extraction
      efficacies with frozen tissues and current leader methodology is presented.
      Quantitative validation of methodology was carried out in a cohort of matched
      tumour/normal, frozen/FFPE renal tissue samples from 10 patients, probed by
      western blotting for a selected panel of seven proteins known to be
      differentially expressed in renal cancer. Our data show that the protocol enables
      efficient extraction of non-degraded, full-length, immunoreactive protein, with
      tumour versus normal differential expression profiles for a majority of the panel
      of proteins tested being comparable to matched frozen tissue controls (rank
      correlation, r = 0.7292, p < 1.825e-09). However, the variability observed in
      extraction efficacies for some membrane proteins emphasizes the need for cautious
      interpretation of quantitative data from this subset of proteins. The method
      provides a viable, cost-effective quantitative option for the validation of
      potential biomarker panels through a range of clinical samples from existing
      diagnostic archives, provided that validation of the method is first carried out
      for the specific proteins under study.

PMID- 19156776
TI  - The development of multiple bladder tumour recurrences in relation to the FGFR3
      mutation status of the primary tumour.
AB  - Non-muscle invasive bladder cancers (NMI-BCs) represent 75% of bladder cancers
      upon presentation. After removal of the primary tumour by transurethral
      resection, multiple recurrences continue to develop in 70% of patients.
      Consequently, prolonged and costly surveillance by cystoscopy is required.
      Mutations in the FGFR3 oncogene are common in NMI-BCs and are associated with a
      lower chance of progression to muscle-invasive disease. Here we analysed the
      consistency of FGFR3 mutations in primary and recurrent tumours. This knowledge
      is of crucial importance if FGFR3 mutation analysis on urinary cells is to be
      used as an alternative for cystoscopical surveillance. To this end, we monitored
      the disease process and FGFR3 mutation status of primary and recurrent tumours in
      118 patients with NMI-BC. During median follow-up of 8.8 years, these patients
      underwent 2133 cystoscopies and 80 patients developed 414 recurrences. FGFR3
      mutations were equally prevalent in primary and recurrent tumours (63%). Patients
      can have different types of FGFR3 mutations in different tumours. Recurrence risk
      was not significantly different for patients with a mutant or wild-type primary
      tumour. Recurrence rates varied widely between patients but were constant for a
      patient and were unrelated to FGFR3 status. In the mutant patient group, in
      contrast to the wild-type group, recurrences continued to develop after 10 years.
      In 81% of the recurrences of patients with a mutant primary tumour, a mutation
      was found. Moreover, recurrences in this patient group were of lower stage and
      grade than those of patients with a wild-type primary tumour (p < 0.001). These
      results suggest that surveillance by FGFR3 mutation analysis on voided urine in
      combination with a reduced cystoscopy frequency of patients presenting with an
      FGFR3 mutant tumour is worth investigating.

PMID- 19156777
TI  - Ccl2/Mcp-1 blockade reduces glomerular and interstitial macrophages but does not
      ameliorate renal pathology in collagen4A3-deficient mice with autosomal recessive
      Alport nephropathy.
AB  - Lack of the alpha3 or alpha4 chain of type IV collagen (COL4) causes autosomal
      recessive Alport nephropathy in humans and mice that is characterized by
      progressive glomerulosclerosis and tubulointerstitial disease. Renal pathology is
      associated with chemokine-mediated macrophage infiltrates but their contribution
      to the progression of Alport nephropathy is unclear. We found Ccl2 to be
      expressed in increasing amounts during the progression of nephropathy in Col4a3
      deficient mice; hence, we blocked Ccl2 with anti-Ccl2 Spiegelmers, biostable L
      enantiomeric RNA aptamers suitable for in vivo applications. Ccl2 blockade
      reduced the recruitment of ex vivo-labelled macrophages into kidneys of Col4a3
      deficient mice. We therefore hypothesized that a prolonged course of Ccl2
      blockade would reduce renal macrophage counts and prevent renal pathology in
      Col4a3-deficient mice. Groups of Col4a3-deficient mice received subcutaneous
      injections of either an anti-mCcl2 Spiegelmer or non-functional control
      Spiegelmer on alternate days, starting from day 21 or 42 of age. Glomerular and
      interstitial macrophage counts were found to be reduced with Ccl2 blockade by 50%
      and 30%, respectively. However, this was not associated with an improvement of
      glomerular pathology, interstitial pathology, or of overall survival of Col4a3
      deficient mice. We conclude that Ccl2 mediates the recruitment of glomerular and
      interstitial macrophages but this mechanism does not contribute to the
      progression of Alport nephropathy in Col4a3-deficient mice.

PMID- 19156778
TI  - A pyrrolysine analogue for protein click chemistry.
AB  - Ignoring the STOP sign: A pyrrolysine analogue bearing a terminal alkyne was site
      specifically incorporated into recombinant calmodulin (CaM) through a UAG codon.
      The resulting protein was labeled with an azide-containing dye using a copper(I)
      catalyzed click reaction. Subsequent application of an orthogonal cysteine
      tagging method yielded a CaM labeled with two distinct fluorophores that enabled
      its study by FRET spectroscopy.

PMID- 19156779
TI  - Primary care mental health: a new frontier for psychology.
AB  - The medical system in this country is divided into primary care and specialty
      care. Mental health is for the most part a specialty service dependent on
      referrals, often from primary care providers. The authors propose a new model
      where psychologists work in collaboration with primary care medical teams. This
      integrated, coordinated model enables psychologists to help patients they would
      not otherwise see in a mental health system. Examples of patients in this
      category are seniors, those with somatizing disorders, and those experiencing the
      challenges of dealing with a chronic illness. This model also enables
      psychologists to provide consultation to the medical teams. In this article, the
      authors discuss the world of the primary care medical team and present the
      rationale for integration or collaboration. They describe the barriers to
      collaborative practices and ways to overcome these barriers. Finally, they
      present practical strategies that psychologists can use on a regular basis to
      increase their collaboration with primary care. These strategies can be used by
      those who work in colocated practices as well as those who work in separate
      locations.

PMID- 19156780
TI  - Receptor-mediated targeting of cathepsins in professional antigen presenting
      cells.
AB  - Tag for professionals: A fluorescently tagged clustered mannoside DCG-04 analogue
      (see structure) is designed and synthesized using a modular approach. Uptake of
      the probe in professional antigen presenting cells and subsequent labeling of
      cathepsins proceeded in a mannose-receptor dependent manner.

PMID- 19156781
TI  - Identifying and screening for psychological and comorbid medical and
      psychological disorders in medical settings.
AB  - There is increased attention to the medical and economic consequences of
      psychological problems comorbid with medical issues. There is also a clear
      awareness that most psychological problems are assessed and responded to in
      nonpsychiatric medical settings. This has furthered interest and attention in
      implementing screening procedures to better identify psychological, behavioral,
      and substance abuse problems in medical settings. Such interest is taking the
      form of recommendations from federal government task forces, and the funding of
      large projects to include screening in medical settings. At the same time there
      has been further attention to brief, valid, and reliable measures with which to
      capture psychological comorbidities. However, there have been multiple concerns
      raised about a variety of issues concerning the utility and effectiveness of such
      screening procedures and the identification of multiple issues to be considered
      in screening design. The author outlines and reviews the rationale and concerns
      about screening, identifies the issues that need to be considered in screening
      program development, and describes the efforts to develop a screening capacity in
      a rural family practice.

PMID- 19156782
TI  - Direct C-H metalation with chromium(II) and iron(II): transition-metal
      host/benzenediide guest magnetic inverse-crown complexes.
AB  - Check M(etal)ate: The chessboard and the figures represent a special reaction in
      which different low-polarity metals can metalate arenes directly when they are
      brought into the right position. In a combination of queen (sodium) and knight
      (chromium or iron), it is possible for the knight (usually the weaker piece) to
      make a direct deadly hit on the king (benzene) in this game of elemental chess.

PMID- 19156783
TI  - A chiral concave-bound cyclopentadienyl iron complex of sumanene.
AB  - Great bowls of fire: The rotation of the cyclopentadienyl (Cp) ring is restricted
      in two concave-bound monoalkyl-substituted [CpFe(eta(6)-sumanene)](+) "pi-bowl"
      complexes (see picture). The asymmetric stacking of atropisomers was observed
      with a MeCpFe complex in the solid state and the chiral (S)-sBuCpFe complex
      showed magnetic and optical desymmetrization of the sumanene ligand, which is the
      first example of a chiral complex of a pi-bowl ligand.

PMID- 19156784
TI  - Plugging a molecular wire into photosystem I: reconstitution of the photoelectric
      conversion system on a gold electrode.
AB  - Plug and play: Photoinduced electron transfer occurs from photoexcited P700 in
      photosystem I (PSI) to a gold surface (see picture). A novel molecular connector
      system is used, in which an artificial molecular wire, which is assembled on the
      gold surface, was plugged into PSI by reconstitution. Analysis of the
      photoelectron transfer kinetics proved both the output of electrons from PSI and
      the effectiveness of the molecular wire.

PMID- 19156785
TI  - Enantiomerically pure chiral {Fe28} wheels.
AB  - Wheels of steel: Two enantiomerically pure chiral {Fe(28)} wheel-like aggregates
      have been synthesized from the acetate buffer solution containing ferric ions and
      chiral tartrate ligands (see picture). These compounds are the largest chiral
      ferric aggregates isolated to date.

PMID- 19156786
TI  - Heparin antagonism by polyvalent display of cationic motifs on virus-like
      particles.
AB  - Particles to the rescue! The construction of cationic amino acid motifs on the
      surface of bacteriophage Qbeta by genetic engineering or chemical conjugation
      gives particles that are potent inhibitors of the anticoagulant action of
      heparin, which is a common anticlotting agent subject to clinical
      overdose.Polyvalent interactions allow biological structures to exploit low
      affinity ligand-receptor binding events to affect physiological responses. We
      describe here the use of bacteriophage Qbeta as a multivalent platform for the
      display of polycationic motifs that act as heparin antagonists. Point mutations
      to the coat protein allowed us to generate capsids bearing the K16M, T18R, N10R,
      or D14R mutations; because 180 coat proteins form the capsid, the mutants provide
      a spectrum of particles differing in surface charge by as much as +540 units
      (K16M vs. D14R). Whereas larger poly-Arg insertions (for example, C-terminal
      Arg(8)) did not yield intact virions, it was possible to append chemically
      synthesized oligo-Arg peptides to stable wild-type (WT) and K16M platforms.
      Heparin antagonism by the particles was evaluated by using the activated partial
      thrombin time (aPTT) clotting assay; this revealed that T18R, D14R, and WT
      (R(8)G(2))(95) were the most effective at disrupting heparin-mediated
      anticoagulation (>95 % inhibition). This activity agreed with measurements of
      zeta potential (ZP) and retention time on cation exchange chromatography for the
      genetic constructs, which distribute their added positive charge over the capsid
      surface (+180 and +360 for T18R and D14R relative to WT). The potent activity of
      WT-(R(8)G(2))(95), despite its relatively diminished overall surface charge is
      likely a consequence of the particle's presentation of locally concentrated
      regions with high positive charge density that interact with heparin's
      extensively sulfated domains. The engineered cationic capsids retained their
      ability to inhibit heparin at high concentrations and showed no anticlotting
      activity of the kind that limits the utility of antiheparin polycationic agents
      that are currently in clinical use.

PMID- 19156787
TI  - The structural diversity of acidic lipopeptide antibiotics.
AB  - Acidic lipopeptide antibiotics are a new class of potent antibiotics, which
      includes daptomycin, A54145, calcium-dependent antibiotics (CDAs),
      friulimicins/amphomycins, laspartomycin/glycinocins and others. The importance of
      this novel class is exemplified by the success story of the clinically approved
      daptomycin, which is used for the treatment of skin infections and bacteremia
      caused by multidrug-resistant bacteria, including methicillin-resistant
      Staphylococcus aureus and vancomycin-resistant enterococci. The potency of acidic
      lipopeptides is inherent in their chemical structure. The nonribosomally
      synthesized peptide cores consist of eleven to 13 amino acids, which are
      rigidified by the formation of a ten-membered ring. An N-terminal fatty acid,
      which facilitates insertion into the lipid bilayer of bacterial membranes,
      completes the structure. All these antibiotics contain multiple nonproteinogenic
      amino acids as well as different lipid tails; this yields remarkable structural
      diversity. This review summarizes the observed structural variety through a
      detailed description of the composition of the acidic lipopeptides. Furthermore,
      engineering approaches towards novel lipopeptides are presented. Recent
      discoveries in the field of tailoring enzymes, which enable structural plurality
      mainly by amino and fatty acid precursor biosynthesis, are highlighted.

PMID- 19156789
TI  - Residual dipolar couplings in short peptidic foldamers: combined analyses of
      backbone and side-chain conformations and evaluation of structure coordinates of
      rigid unnatural amino acids.
AB  - A flexible tool for rigid systems. Residual dipolar couplings (RDCs) have proven
      to be valuable NMR structural parameters that provide insights into the backbone
      conformations of short linear peptidic foldamers, as illustrated here. This study
      demonstrates that RDCs at natural abundance can provide essential structural
      information even in the case of short linear peptides with unnatural amino acids.
      In addition, they allow for the detection of proline side-chain conformations and
      are used as a quality check for the parameterizations of rigid unnatural amino
      acids.

PMID- 19156788
TI  - Synthesis of sulfated glucosaminides for profiling substrate specificities of
      sulfatases and fungal beta-N-acetylhexosaminidases.
AB  - Systematic sulfation: Sulfated glycoconjugates are degraded either by desulfation
      followed by glycoside cleavage, or by glycoside cleavage followed by desulfation.
      To study these processes, here we report the synthesis of four regioisomerically
      sulfated p-nitrophenyl glucosaminides from the common precursor p-nitrophenyl N
      acetyl-beta-D-glucosaminide. These substrates allowed the rapid analysis of the
      substrate preferences of a set of four sulfatases and 24 hexosaminidases.Sulfated
      carbohydrates are components of many glycoconjugates, and are degraded by two
      major processes: cleavage of the sulfate ester by a sulfatase, or en bloc removal
      of a sulfated monosaccharide by a glycoside hydrolase. However, these processes
      have proved difficult to study owing to a lack of homogeneous, defined
      substrates. We describe here the synthesis of a series of p-nitrophenyl beta-D
      glucosaminides bearing sulfate esters at the 2-, 3-, 4- or 6-positions, by
      divergent routes starting with p-nitrophenyl 2-acetamido-2-deoxy-beta-D
      glucopyranoside. The sulfated p-nitrophenyl beta-D-glucosaminides were used to
      study the substrate specificity of four sulfatases (from Helix pomatia, Patella
      vulgata, abalone, and Pseudomonas aeruginosa), and revealed significant
      differences in the preference of each of these enzymes for desulfation at
      different positions around the sugar ring. The 3-, 4- and 6-sulfated p
      nitrophenyl 2-acetamido-2-deoxy-beta-D-glucosaminides were screened against a
      panel of 24 fungal beta-N-acetylhexosaminidases to assess their substrate
      specificity. While the 4- and 6-sulfates were substrates for many of the fungal
      enzymes investigated, only a single beta-N-acetylhexosaminidase, that from
      Penicillium chrysogenum, could hydrolyze the 3-sulfated p-nitrophenyl glycoside.
      Together these results demonstrate the utility of sulfated p-nitrophenyl beta-D
      glucosaminides for the study of both sulfatases and glycoside hydrolases.

PMID- 19156790
TI  - A facile method to assemble PNIPAM-containing microgel photonic crystals.
AB  - Structural colors: Poly(N-isopropyl acrylamide) based microgel photonic crystals
      are fabricated by using a new method called "high-temperature-induced hydrophobic
      assembly". The assembling conditions affect the water content of the crystals,
      thus determining their structural color (see image). The obtained photonic
      crystals are sensitive to solvents, and the reversible changes in their color can
      be observed with the naked eye.

PMID- 19156791
TI  - Reversible storage of lithium in a rambutan-like tin-carbon electrode.
AB  - Fruity electrodes: A simple bottom-up self-assembly method was used to fabricate
      rambutan-like tin-carbon (Sn@C) nanoarchitecture (see scheme, green Sn) to
      improve the reversible storage of lithium in tin. The mechanism of the growth of
      the pear-like hairs is explored.

PMID- 19156792
TI  - Proteomic analysis of plasma membrane vesicles.
AB  - A simple and scalable method is presented for harvesting, purification, and on
      chip processing of mammalian plasma membrane vesicles (PMVs) optimized for
      downstream proteome analysis. After immobilization on a microfluidic flowcell of
      PMVs, the embedded membrane proteins are proteolytically digested, and the
      peptides harvested and analyzed by LC-MS/MS. Over 93% of the detected proteins
      are plasma-membrane-derived.

PMID- 19156793
TI  - Size-dependent ordering of liquid crystals observed in polymeric capsules with
      micrometer and smaller diameters.
AB  - Made to order: Aqueous dispersions of polymer-encapsulated liquid crystal (LC)
      droplets were synthesized with precise interfacial chemistry and sizes in the
      micrometer-to-sub-micrometer range. Size-dependent changes in LC ordering could
      be observed. Study of the competition between size and interfacial chemistry on
      LC ordering enables size-dependent properties of LC droplets to be exploited in
      applications such as photonics and sensing.

PMID- 19156794
TI  - Mode of action and design rules for additives that modulate crystal nucleation.
AB  - Molecular dynamics simulations reveal that the key factors that determine the
      ability of an additive to modulate crystal nucleation are the strength of its
      interaction with the solute, its disruptive ability (which may be based on
      steric, entropic, or energetic effects), and interfacial properties, along with
      its ability to serve as a template for nucleation (see snapshot of an emerging
      nucleus with a single-particle additive: black spheres).

PMID- 19156795
TI  - Electronic absorption spectra and redox properties of C type cytochromes in
      living microbes.
AB  - Shewanella is an electrogenic microbe that has significant content of c type
      cytochromes (ca. 0.5 mM). This feature allows the optical absorption spectra of
      the cell-membrane-associated proteins to be monitored in vivo in the course of
      extracellular respiratory electron-transfer reactions. The results show
      significant differences to those obtained in vitro with purified proteins.

PMID- 19156796
TI  - Metal-ion selectivity of chemically modified uracil pairs in DNA duplexes.
AB  - DNA duplexes containing 5-modified uracil pairs (5-bromo, 5-fluoro, and 5
      cyanouracil) bind selectivity to metal ions. Their selectivity is sensitive to
      the pH value of the solution (see picture), as the acidities of the modified
      uracil bases vary according to the electron-withdrawing properties of the
      substituents.

PMID- 19156797
TI  - Metal silylenes generated by double silicon-hydrogen activation: key
      intermediates in the rhodium-catalyzed hydrosilylation of ketones.
AB  - Rhodium silylenes, which are generated by double Si-H activation at the metal,
      are involved in a low-activation-barrier mechanism of the hydrosilylation of
      ketones with R(2)SiH(2). A DFT-based study of reaction mechanisms accounts for
      the experimental observations, notably the rate enhancement for R(2)SiH(2) over
      R(3)SiH and an inverse kinetic isotope effect.

PMID- 19156798
TI  - Effects of monomer functionality on switchable holographic gratings formed in
      polymer-dispersed liquid-crystal cells.
AB  - We investigate the effects of monomer functionality on the formation and
      switching characteristics of holographic transmission gratings in polymer
      dispersed liquid-crystal cells fabricated by using the 633 nm wavelength of an He
      Ne laser. We present results for the microstructure, diffraction efficiency eta,
      and switching characteristics of gratings formed with acrylate monomers of
      functionalities ranging from 2 to 4. The microstructure and diffraction
      efficiency are sensitive to functionality; both improve with increasing
      functionality. For functionalities of 2.5 or more, eta approaches 34% and can be
      switched off with electric fields of about 20 MV m(-1).

PMID- 19156799
TI  - Decoupling 2D inter- and intrachain energy transfer in conjugated polymers.
AB  - The dimensionality of conjugated polymer systems plays an important role in
      energy-transfer processes, and 1D and 2D energy transfer of excitations are
      typically much slower than that between pi-stacked chains within a 3D polymeric
      solid. However, whether 2D energy transfer in conjugated polymers occurs mainly
      along polymer chains (intrachain), or between in-plain-adjacent polymer chains
      (interchain), has yet to be determined due to the difficulty of experimentally
      decoupling inter- and intrachain interaction in a 2D polymer system. This can be
      achieved by incorporating conjugated polymer chains into the planar galleries of
      layered matrices which sterically hinder polymer aggregation and pi-pi interchain
      interactions. Here, pristine blue-emitting polyfluorene chains and polyfluorene
      chains with known concentrations of green-emitting on-chain fluorenone defects
      are either separately or collectively incorporated into layered SnS(2). X-ray
      powder diffraction of the composite films confirms incorporation of the polymer
      chains into the layered galleries. Monitoring the fluorene-to-fluorenone energy
      transfer as a function of fluorenone concentration and distribution in the
      layered galleries allows differentiation between inter- and intrachain fluorene
      fluorenone energy transfer. It is found that, 2D energy transfer in conjugated
      polymers follows mainly an interchain process, despite the absence of pi-pi
      interchain interactions.

PMID- 19156800
TI  - Two-color two-photon excitation of intrinsic protein fluorescence: label-free
      observation of proteolytic digestion of bovine serum albumin.
AB  - Two-color two-photon (2c2p) excitation fluorescence is used to monitor the
      enzymatic cleavage of bovine serum albumin (BSA) by subtilisin. Fluorescence is
      generated by irradiation with spatially and temporally overlapping femtosecond
      laser beams resulting in simultaneous absorption of an 800 and a 400 nm photon.
      Thereby, excitation of the fluorescent amino acid tryptophan present in BSA
      corresponds to an effective one-photon wavelength of 266 nm. The progress of
      protein cleavage is monitored by time-resolved fluorescence analysis. The
      fluorescence lifetime of tryptophan decreases during the reaction. This
      demonstrates a novel label-free multiphoton observation technique for
      conformational changes of proteins containing tryptophan. Due to the strong 2c2p
      fluorescence signal it is suitable for fast evaluation and monitoring of protein
      reactions. The course of the reaction is monitored simultaneously by gel
      electrophoresis. In contrast to conventional one-photon techniques, 2c2p
      excitation enables label-free protein fluorescence studies without irradiating
      the sample with UV light. Due to the dependence of the excitation on the power of
      both laser beams, excitation is limited to a relatively small focal volume. This
      results in dramatically reduced overall photodamage compared to direct UV
      irradiation. This method can be easily extended to microscopy imaging techniques.

PMID- 19156801
TI  - Supramolecular "double-propeller" dimers of hexanuclear Cu(II)/Ln(III) complexes:
      a {Cu3Dy3}2 single-molecule magnet.
AB  - Propelling magnetism: Supramolecular organization leads to a remarkable
      dodecanuclear {Cu(3)Dy(3)}(2) cluster with a "double-propeller" shape (see
      picture). The linkages of the CuDy units, both intramolecular and supramolecular,
      appear to be responsible for a drastic change in the single molecule magnetic
      behavior.

PMID- 19156802
TI  - Artificial ribozyme switches containing natural riboswitch aptamer domains.
AB  - RNA Lego: The use of natural riboswitch aptamers in synthetic RNA switches (see
      picture) should broaden the scope of artificial RNA regulators dramatically. It
      is shown that thiamine pyrophosphate (TPP) aptamers can be used in engineered
      devices as very sensitive switches of gene expression in unmodified organisms.
      The approach demonstrates that intrinsic metabolites can be utilized as external
      effectors of cellular functions.

PMID- 19156804
TI  - The effect of a complexed lithium cation on a norcarane-based radical clock.
AB  - Density-functional theory (DFT) and ab initio calculations have been used to
      investigate the effect of a complexed lithium cation on the radical-clock
      rearrangement of the 2-norcaranyl radical to the 3-cyclohexenylmethyl radical. As
      found earlier for ring-closing radical clocks, complexation with a metal ion
      leads to a significant lowering of the barrier to rearrangement. DFT calculations
      on a model for the norcaranyl clock in cytochrome P450 confirm the two-state
      reactivity proposal of Shaik et al. and indicate that the porphyrin exerts little
      or no electrostatic effect on the rearrangement barrier.

PMID- 19156803
TI  - Protein-functionalized synthetic antiferromagnetic nanoparticles for biomolecule
      detection and magnetic manipulation.
AB  - Direct protein functionalization provides synthetic antiferromagnetic
      nanoparticles with high chemical specificity and multifunctionality. These
      nanoparticle-protein conjugates function as improved magnetic labels for
      biological detection experiments, and exhibit tunable responses to a small
      external magnetic field gradient, thus allowing the observation of distinctive
      single nanoparticle motion.

PMID- 19156805
TI  - Synthesis and optoelectronic properties of nanometer-sized and highly soluble
      homocoupled oligodiacetylenes.
AB  - A new series of pure, nanometer-sized and highly-soluble homocoupled
      oligodiacetylenes (HODA) consisting of two symmetrical oligodiacetylene units was
      synthesized with high yield and on a multi-milligram scale under mild, catalytic
      Sonogashira conditions. The lambda(max) and the epsilon(max) of absorption for
      these HODAs show an increase with the chain elongation. The lambda(max) converges
      to 450 nm for the longest members of the series at micromolar concentration and
      to 462 nm for thin drop-casted films. An additional red-shifted absorption is
      observed in the solid state and in solution at low temperatures, which is caused
      by aggregation. The lambda(max) of the fluorescence emission increases with the
      chain length and reaches 492 nm for the longest oligomer. The fluorescence
      quantum yield has its maximum for the shortest oligomer and decreases rapidly for
      the longer ones. A similar trend is found for the fluorescence lifetime with a
      maximum of 100 ps for the homocoupled monomer. The rotational correlation time
      shows a linear increase with the oligomer length. This reveals a significant
      persistence length and indicates that the HODA molecules are fully stretched
      molecular rods (up to 8.2 nm).

PMID- 19156806
TI  - Proton pump for O2 reduction catalyzed by 5,10,15,20
      tetraphenylporphyrinatocobalt(II).
AB  - The role of 5,10,15,20-tetraphenylporphyrinatocobalt(II) ([Co(tpp)]) as a
      catalyst on molecular oxygen (O(2)) reduction by ferrocene (Fc) and its two
      derivatives, 1,1'-dimethylferrocene (DFc) and decamethylferrocene (DMFc) at a
      polarized water|1,2-dichloroethane (DCE) interface has been studied. The
      water|DCE interface essentially acts as a proton pump controlled by the Galvani
      potential difference across the interface, driving the proton transfer from water
      to DCE. [Co(tpp)] catalyzed O(2) reduction by Fc, DFc and DMFc is then followed
      to produce hydrogen peroxide (H(2)O(2)). The catalytic mechanism is similar to
      that proposed by Fukuzumi et al. for bulk reactions. This interfacial system
      provides a platform for a very efficient collection of H(2)O(2), by extraction
      immediately after its formation in DCE to the adjacent water phase, thus
      decreasing the possibility of degradation and further reaction with ferrocene
      derivatives.

PMID- 19156807
TI  - Spectroscopy probing of the formation, recognition, and conversion of a G
      quadruplex in the promoter region of the bcl-2 oncogene.
AB  - This study has demonstrated the formation of the G-quadruplex structure from the
      G-rich sequence in the promoter region of the bcl-2 oncogene; the formation could
      be induced by addition of NH(4)(+) or K(+) ions. The binding affinity and
      stoichiometry of seven small molecules with the G-quadruplex were examined by
      using ESI-MS, as well as CD and UV spectroscopy. The binding-affinity order was
      determined to be P1 approximately = P5 > P2 > P3 approximately = P4 > P7 > P6. In
      particular, the small-molecule induction of the structural transition between the
      G-quadruplex and duplex DNA forms in this promoter region was investigated by ESI
      MS. We directly observed specific binding of dehydrocorydaline (P7) and cationic
      porphyrin (P5) in one system consisting of the G-quadruplex and the duplex DNA,
      respectively. The results indicate that P7 selectively stabilizes the G
      quadruplex and shifts the equilibrium toward G-quadruplex formation of the bcl-2
      promoter, whereas P5 converts the G-quadruplex into the duplex DNA, which results
      in strong and selective binding to the duplex form. Therefore, P5 and P7 with
      their attractive binding specificities could be considered as precursors for
      pathway-specific drug design for regulation of bcl-2 oncogene transcription.

PMID- 19156808
TI  - A ratiometric fluorescent probe for hypochlorite based on a deoximation reaction.
AB  - In this work, we have successfully provided a novel strategy for the rational
      design and synthesis of a ratiometric fluorescent probe for hypochlorite. The
      strategy is based on the deoximation reaction, which has not yet been used in the
      fluorescent hypochlorite probe design. Interestingly, the probe showed a
      ratiometric fluorescent response to hypochlorite with the emission intensities
      ratio (I(509)/I(439)) increasing from 0.28 to 2.74. Furthermore, the probe
      displayed high selectivity for hypochlorite over other species due to the
      distinct deoximation conditions. The probe developed herein represents the first
      ratiometric fluorescent probe for hypochlorite.

PMID- 19156809
TI  - Remarkably slow rotation about a single bond between an sp(3)-hybridised carbon
      atom and an aromatic ring without ortho substituents.
AB  - Look, no ortho substituents! A series of polycycles were prepared by using a
      three-component Joullie-Ugi reaction. The rate of rotation about the bond between
      a highly hindered bridgehead and a phenyl ring with no ortho substituents was
      measured, and was highly dependent on the substitution. Rotamer half-lives of up
      to 21 h at 298 K were observed (see figure). Rotamers resulting from this
      restricted rotation were isolated for the first time.A series of polycycles was
      prepared by using a three-component Joullie-Ugi reaction. The rate of rotation
      about the bond between a highly hindered bridgehead and a phenyl ring with no
      ortho substituents was measured by using, in general, variable-temperature HPLC.
      The rate of rotation was highly dependent on substitution and rotamer half-lives
      of up to 21 h at 298 K were observed. Insights into the effect of substitution on
      the rate of rotation were gleaned through electronic structure calculations on
      closely related derivatives. Rotamers resulting from restricted rotation about a
      bond between an sp(3)-hybridised carbon atom and a phenyl ring with no ortho
      substituents were isolated for the first time, and the equilibration of the
      separated rotamers was followed by using analytical HPLC. It was demonstrated,
      for the first time, that a highly hindered environment for the sp(3)-hybridised
      atom is sufficient for slow bond rotation about a single bond between sp(3)- and
      sp(2)-hybridised carbon atoms.

PMID- 19156810
TI  - Single-crystalline molybdenum trioxide nanoribbons: photocatalytic,
      photoconductive, and electrochemical properties.
AB  - Large-scale, high-purity and uniform alpha-MoO(3) nanoribbons have been
      synthesized by a facile hydrothermal route without employing surfactants or
      templates. The as-prepared alpha-MoO(3) nanoribbons were up to several
      micrometers in length, 100 nm in width, 15-20 nm in thickness, and grew along the
      [001] direction. The obtained nanoribbons exhibited a quantum size effect in
      optical properties, showing a blue shift of the band gap and direct transitions
      compared with the values of bulk MoO(3). The nanoribbons also showed superior
      photocatalytic ability in the photodegradation reaction of an aqueous solution of
      Rhodamine B under visible light. Furthermore, the as-prepared alpha-MoO(3)
      materials exhibited linear current-voltage (I-V) characteristics and excellent
      photoresponse. As the light source was switched on and off, the currents could be
      reversibly switched between high and low value at the voltage of 0.1 V.
      Electrochemical measurements predicted that the alpha-MoO(3)/carbon fiber
      modified microelectrode would display excellent electrochemical characters and
      high sensitivity toward neurotransmitter dopamine. The modified electrode was
      also quite stable and had good reproducibility, which might have application in
      the electrochemical analysis.

PMID- 19156811
TI  - Nucleation and growth of CeF(3) and NaCeF(4) nanocrystals.
AB  - Studying growth: The diffusion-controlled kinetic (DCK) model and the surface
      chemical thermodynamics (SCT) model have been successfully applied to interpret
      the nucleation and growth mechanism of CeF(3) (see TEM images) and NaCeF(4)
      nanocrystals, and may generally give light to the size-control and morphology
      prediction of rare-earth fluorides at the nanoscale level.Monodisperse CeF(3) and
      NaCeF(4) nanocrystals have been synthesized by using the liquid-solid-solution
      (LSS) approach. The nucleation and growth of nanocrystalline CeF(3) and NaCeF(4)
      were controlled by both kinetics and thermodynamics, which can be investigated by
      the diffusion-controlled kinetic (DCK) model and surface chemical thermodynamics
      (SCT) theory. The DCK and SCT models were introduced to explain how the ripening
      time, reaction temperature, and initial concentrations affected the size
      transition of CeF(3) and NaCeF(4) nanocrystals in detail. Also, these models are
      believed to be universal and can be applied to explore the morphology evolution
      of almost all rare-earth fluoride nanocrystals.

PMID- 19156812
TI  - para-Functionalized aryl-di-tert-butylfluorosilanes as potential labeling
      synthons for (18)F radiopharmaceuticals.
AB  - Broad spectrum: Novel para-functionalized aryl-di-tert-butylfluorosilanes, p
      (tBu(2)FSi)C(6)H(4)X (X=functional group), have been made available and broaden
      the spectrum of silicon-based (18)F acceptors (SiFAs) for potential PET
      applications. For example, the [(18)F]maleimido derivative 1 has been employed
      for the synthesis of [(18)F]1- labeled rat serum albumin (RSA), the applicability
      of which for PET has been verified by in vivo experiments.The syntheses of the
      functionalized triorganofluorosilanes tBu(2)(p-XC(6)H(4))SiF (3 a, X=SH; 4 a,
      X=NCS; 4 b, X=NCO; 5, X=NC(4)H(2)O(2); 7, X=COOH; 8 a, X=COONC(4)H(4)O(2); 8 b,
      X=COOC(6)F(5)) are reported. These compounds display potential as silicon-based
      fluoride acceptors (SiFAs). The molecular structures of compounds 5, 7, and 8 a
      have been determined by single-crystal X-ray diffraction studies. With the
      exception of compounds 8 a and 8 b, all of the compounds could be (18)F-labeled
      by isotopic exchange in good to high radiochemical yields (RCY) with good to
      excellent specific activities. As proof of applicability, the maleimido
      functionalized SiFA derivative 5, which is specific for thiol groups, has been
      used for the labeling of rat serum albumin (RSA) that had been derivatized with 2
      iminothiolane. The incorporation of [(18)F]5 into the derivatized RSA reached a
      maximum yield after 30 min at ambient temperature. After purification, the
      [(18)F]RSA was evaluated in a healthy rat by means of muPET and displayed an
      expedient in vivo stability over 180 min.

PMID- 19156813
TI  - Chiral poly(4-ethynylbenzoyl-l-valine)-induced helical self-assembly of
      alkynylplatinum(II) terpyridyl complexes with tunable electronic absorption,
      emission, and circular dichroism changes.
AB  - A chiral amino acid-containing polyacetylene, poly(4-ethynylbenzoyl-L-valine),
      was found to induce the aggregation and self-assembly of square-planar
      alkynylplatinum(II) terpyridyl complexes by electrostatic binding of the
      positively charged metal complexes to the anionic sites of the polyacetylene, as
      revealed by the appearance of new UV/Vis absorption and emission bands upon
      mixing under basic conditions. The induced complex self-assembly was found to be
      influenced by the polyacetylene and/or base concentration, and the effect of pH
      on the reversibility of the aggregate/monomer interconversion was also studied.
      The conformational changes of the polyacetylene were probed by circular dichroism
      (CD) spectroscopy, in which the chirality signal of the corresponding chain
      helicity in the presence of the base was enhanced and stabilized upon addition of
      the platinum(II) complexes. The induced complex aggregation was dependent on the
      structural properties of the polyacetylene, while the chirality of the
      polyacetylene was strongly influenced by the introduction of the complex.

PMID- 19156814
TI  - Supramolecular templates for nanoflake-metal surfaces.
AB  - A sustainable method for the fabrication of metallic surfaces with flower-like
      fractal morphology was developed by using a three-dimensional supramolecular
      assembly as a template. Modifying Au nanoflakes with self-assembled monolayers or
      polymers allows the surface wettability to be adjusted from superhydrophobic to
      superhydrophilic (see figure). Furthermore, Au nanoflakes present excellent
      substrates for surface-enhanced Raman spectroscopy (SERS).

PMID- 19156815
TI  - Enzymatic esterification in aqueous miniemulsions.
AB  - Monoesters of various linear carboxylic acids (C7-C12) with omega-phenyl-labeled
      primary alcohols (C1-C5) were synthesized in aqueous miniemulsions with various
      lipases as biocatalysts. The reactants were dispersed in an aqueous solution of a
      nonionic surfactant to form long-term stable miniemulsions. The esterification of
      all of the systems could be catalyzed by the applied enzyme and yielded
      significant conversions of about 90%. The hydrophilicity of the reactants and the
      specificity of the enzyme toward the substrates determine the reaction velocity
      and the final conversion. As a model system the reaction of nonanoic acid and 3
      phenylpropanol was extensively studied. Among various lipases, Lipase PS was
      determined to be the most effective, and for this reaction the parameters were
      optimized. A maximum conversion of 80% could be obtained in less than one hour of
      reaction time. In comparison with an acid-catalyzed esterification performed in
      miniemulsion with the same reaction parameters, the enzyme-catalyzed reaction
      showed a significantly faster conversion. The reactions proved that the
      application of the miniemulsion technique enables efficient direct enzyme
      catalyzed esterification reactions from carboxylic acids and alcohols in the
      presence of large amounts of water.

PMID- 19156816
TI  - Energy transfer followed by electron transfer in a porphyrin macrocycle and
      central acceptor ligand: a model for a photosynthetic composite of the light
      harvesting complex and reaction center.
AB  - A system that models a photosynthetic composite of the light-harvesting complex
      and reaction center is reported in which light energy collected by cyclic antenna
      porphyrins is transferred to a central energy-acceptor porphyrin, followed by
      photoinduced electron transfer to a fullerene positioned above the ring plane.
      Pyridyl tripodal ligands appended with bis(phenylethynyl)porphyrinatozinc(II)
      (ZnP-Tripod) and additional fulleropyrrolidine moieties (C(60)-ZnP-Tripod) were
      synthesized as the reaction center units. The tripodal ligand was strongly
      accommodated by the light-harvesting porphyrin macrocycle N-(1-Zn)(3) (1-Zn =
      trisporphyrinatozinc(II)) by using three-point coordination of pyridyl to
      uncoordinated porphyrinatozinc sites to afford a stable 1:1 composite. The
      binding constants for ZnP-Tripod and C(60)-ZnP-Tripod in benzonitrile were
      estimated from steady-state fluorescence titrations to be 1.4x10(7) and 1.6x10(7)
      M(-1), respectively. The steady-state fluorescence titration, fluorescence
      lifetime, and transient absorption studies revealed that in both composites the
      excitation energy collected by the nine porphyrins of N-(1-Zn)(3) was efficiently
      transferred to a ZnP moiety by means of a through-space mechanism with a quantum
      yield of approximately 90%. Furthermore, in the composite with C(60)-ZnP-Tripod,
      the converged energy at the ZnP moiety induced electron transfer to the C(60)
      moiety, which afforded the stable charge-separated state (Phi(CS)>90%).

PMID- 19156817
TI  - Nucleotide-dependence of G-actin conformation from multiple molecular dynamics
      simulations and observation of a putatively polymerization-competent superclosed
      state.
AB  - The assembly of monomeric G-actin into filamentous F-actin is nucleotide
      dependent: ATP-G-actin is favored for filament growth at the "barbed end" of F
      actin, whereas ADP-G-actin tends to dissociate from the "pointed end." Structural
      differences between ATP- and ADP-G-actin are examined here using multiple
      molecular dynamics simulations. The "open" and "closed" conformational states of
      G-actin in aqueous solution are characterized, with either ATP or ADP in the
      nucleotide binding pocket. With both ATP and ADP bound, the open state closes in
      the absence of actin-bound profilin. The position of the nucleotide in the
      protein is found to be correlated with the degree of opening of the active site
      cleft. Further, the simulations reveal the existence of a structurally well
      defined, compact, "superclosed" state of ATP-G-actin, as yet unseen
      crystallographically and absent in the ADP-G-actin simulations. The superclosed
      state resembles structurally the actin monomer in filament models derived from
      fiber diffraction and is putatively the polymerization competent conformation of
      ATP-G-actin.

PMID- 19156818
TI  - Dissection of the critical binding determinants of cellular retinoic acid binding
      protein II by mutagenesis and fluorescence binding assay.
AB  - The binding of retinoic acid to mutants of Cellular Retinoic Acid Binding Protein
      II (CRABPII) was evaluated to better understand the importance of the direct
      protein/ligand interactions. The important role of Arg111 for the correct
      structure and function of the protein was verified and other residues that
      directly affect retinoic acid binding have been identified. Furthermore, retinoic
      acid binding to CRABPII mutants that lack all previously identified interacting
      amino acids was rescued by providing a carboxylic acid dimer partner in the form
      of a Glu residue.

PMID- 19156819
TI  - Refining near-native protein-protein docking decoys by local resampling and
      energy minimization.
AB  - How to refine a near-native structure to make it closer to its native
      conformation is an unsolved problem in protein-structure and protein-protein
      complex-structure prediction. In this article, we first test several scoring
      functions for selecting locally resampled near-native protein-protein docking
      conformations and then propose a computationally efficient protocol for structure
      refinement via local resampling and energy minimization. The proposed method
      employs a statistical energy function based on a Distance-scaled Ideal-gas
      REference state (DFIRE) as an initial filter and an empirical energy function
      EMPIRE (EMpirical Protein-InteRaction Energy) for optimization and re-ranking.
      Significant improvement of final top-1 ranked structures over initial near-native
      structures is observed in the ZDOCK 2.3 decoy set for Benchmark 1.0 (74% whose
      global rmsd reduced by 0.5 A or more and only 7% increased by 0.5 A or more).
      Less significant improvement is observed for Benchmark 2.0 (38% versus 33%).
      Possible reasons are discussed.

PMID- 19156821
TI  - Isoform-specific variation in the intrinsic disorder of the ecdysteroid receptor
      N-terminal domain.
AB  - The Drosophila melanogaster ecdysteroid receptor (EcR) is a member of the nuclear
      hormone receptor superfamily. EcR controls animal development and metamorphosis
      by activating or repressing the transcription of target genes. There are three
      EcR isoforms, EcRA, EcRB1, and EcRB2 that exhibit diverse spatial and temporal
      distributions within various tissues and reveal essential functional differences.
      These differences can be attributed to the isoform-specific N-terminal domains
      (NTDs), which differ in length and primary structure. To lay a foundation for
      understanding of the molecular mechanism underlying functional diversity of the
      isoforms, we have carried out a comprehensive biochemical and biophysical
      analysis of purified hexahistidine-tagged EcRA and EcRB1 NTDs (EcRA-NTD and EcRB1
      NTD). The results, along with in silico examinations of the primary structures
      indicate that the EcR NTDs exhibit properties of premolten globule-like
      intrinsically disordered proteins. Furthermore, we demonstrate for the first time
      that NTDs of isoforms of a particular nuclear hormone receptor exhibit distinct
      structural properties. In silico analysis revealed that the EcRA-NTD sequence has
      a bigger tendency for disorder than the EcRB1-NTD sequence. Accordingly, the
      circular dichroism experiments demonstrated that EcRA-NTD has lower regular
      secondary structure content than EcRB1-NTD and the size-exclusion chromatography
      showed that EcRA-NTD is less compact than EcRB1-NTD. Furthermore, the limited
      proteolysis analysis revealed that the C-terminal region common to both NTDs is
      more susceptible to the enzymatic cleavage in EcRA-NTD than in EcRB1-NTD. We
      postulate that unique conformational states of EcRA-NTD and EcRB1-NTD might act
      as the starting points for the functional diversity of EcRA and EcRB1 isoforms.

PMID- 19156822
TI  - Vibrational spectroscopy--a powerful tool for the rapid identification of
      microbial cells at the single-cell level.
AB  - Rapid microbial detection and identification with a high grade of sensitivity and
      selectivity is a great and challenging issue in many fields, primarily in
      clinical diagnosis, pharmaceutical, or food processing technology. The tedious
      and time-consuming processes of current microbiological approaches call for
      faster ideally on-line identification techniques. The vibrational spectroscopic
      techniques IR absorption and Raman spectroscopy are noninvasive methods yielding
      molecular fingerprint information; thus, allowing for a fast and reliable
      analysis of complex biological systems such as bacterial or yeast cells. In this
      short review, we discuss recent vibrational spectroscopic advances in microbial
      identification of yeast and bacterial cells for bulk environment and single-cell
      analysis. IR absorption spectroscopy enables a bulk analysis whereas micro-Raman
      spectroscopy with excitation in the near infrared or visible range has the
      potential for the analysis of single bacterial and yeast cells. The inherently
      weak Raman signal can be increased up to several orders of magnitude by applying
      Raman signal enhancement methods such as UV-resonance Raman spectroscopy with
      excitation in the deep UV region, surface enhanced Raman scattering, or tip
      enhanced Raman scattering.

PMID- 19156823
TI  - Recent advances in the analysis of individual microbial cells.

PMID- 19156824
TI  - Epithelioid angiomyolipoma of the liver with striking giant cell component: fine
      needle aspiration biopsy findings of a rare neoplasm.
AB  - Angiomyolipoma (AML) is a uncommon benign neoplasm of the liver with cyto- and
      histologic features similar to the more commonly encountered renal AML. Tumors
      composed predominantly of epithelioid cells have been referred to as epithelioid
      AML. Because most liver lesions are first evaluated by fine-needle aspiration
      biopsy (FNAB), it is important to distinguish this variant of AML from more
      common hepatic neoplasms such as hepatocellular carcinoma (HCC) or metastatic
      tumors. Rare reports of epithelioid AML of the liver diagnosed by FNAB are in the
      literature. Here, we describe the cytologic findings of a unique case of
      epithelioid AML with numerous giant cells.

PMID- 19156825
TI  - Swelling on the tongue: a rare presentation of oral cysticercosis.

PMID- 19156826
TI  - Fine-needle aspiration biopsy of a papillary thyroid carcinoma involved by
      malignant plasma cell disease: a case report.
AB  - We described the fine-needle aspiration biopsy findings in a case of papillary
      thyroid carcinoma involved by a malignant plasma cell disease of the thyroid
      gland in a 54-year-old female. Although papillary thyroid carcinoma is the most
      common malignant tumor of the thyroid gland, involvement by plasma cell disease
      is exceptionally unusual.

PMID- 19156827
TI  - Medullary thyroid carcinoma presenting as rectangular cell type on fine-needle
      aspiration.
AB  - Medullary thyroid carcinoma typically presents as dyscohesive plasmacytoid,
      spindled, or polygonal cells on fine-needle aspiration smears. We recently
      encountered a case of sporadic medullary thyroid carcinoma that presented as a
      hypercellular aspirate composed of cohesive aggregates of rectangle-shaped cells.
      The case was mistakenly reported as a hypercellular follicular neoplasm on
      cytology. Subsequent thyroidectomy revealed medullary carcinoma. We draw
      attention to this distinctive rectangular cell type as an additional morphology
      for medullary thyroid carcinoma.

PMID- 19156828
TI  - Extranodal lymphomas: review of clinicopathologic and cytologic features.
AB  - Extranodal lymphomas can be challenging for a practicing cytopathologist,
      especially in the fine needle aspiration clinic setting. These lymphomas can vary
      in type from one extranodal site to another. A variety of these lymphomas have
      very specific clinicopathologic features. They also may be associated with
      underlying autoimmune diseases, immunodeficiency syndromes, infection, or be
      noted in unique ethnic communities. This article reviews some of the commonly
      encountered lymphomas in extranodal sites with an emphasis on clinicopathologic
      and cytologic features.

PMID- 19156829
TI  - A strained DNA binding helix is conserved for site recognition, folding
      nucleation, and conformational modulation.
AB  - Nucleic acid recognition is often mediated by alpha-helices or disordered regions
      that fold into alpha-helix on binding. A peptide bearing the DNA recognition
      helix of HPV16 E2 displays type II polyproline (PII) structure as judged by pH,
      temperature, and solvent effects on the CD spectra. NMR experiments indicate that
      the canonical alpha-helix is stabilized at the N-terminus, while the PII forms at
      the C-terminus half of the peptide. Re-examination of the dihedral angles of the
      DNA binding helix in the crystal structure and analysis of the NMR chemical shift
      indexes confirm that the N-terminus half is a canonical alpha-helix, while the C
      terminal half adopts a 3(10) helix structure. These regions precisely match two
      locally driven folding nucleii, which partake in the native hydrophobic core and
      modulate a conformational switch in the DNA binding helix. The peptide shows only
      weak and unspecific residual DNA binding, 10(4)-fold lower affinity, and 500-fold
      lower discrimination capacity compared with the domain. Thus, the precise side
      chain conformation required for modulated and tight physiological binding by HPV
      E2 is largely determined by the noncanonical strained alpha-helix conformation,
      "presented" by this unique architecture. (c) 2009 Wiley Periodicals, Inc.
      Biopolymers 91: 432-443, 2009.

PMID- 19156830
TI  - Molecular dynamics (MD) simulations of VIP and PACAP27.
AB  - Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating
      polypeptide-27 (PACAP27) are members of the secretin-glucagon family containing
      28 and 27 residues, respectively. NMR spectroscopy studies suggest that the N
      terminus exhibit consecutive beta-turns whereas the central and C-terminal parts
      of the VIP molecule have been characterized as being two alpha-helices. In
      contrast, similar studies carried out on PACAP suggest that the shortest active
      peptide segment PACAP27 in the presence of trifluoroethanol (TFE) exhibits a
      disordered N-terminal domain followed by a alpha-helix expanding residues 9-26
      with a discontinuity between residues 20 and 21. In the present study, a series
      of MD trajectories of VIP and PACAP27 were carried out using two different
      implicit models of the solvent: the Generalized Born that use an effective Born
      radii described by Onufriev, Bashford, and Case (GBOBC) and the Hawkins, Cramer,
      and Truhlar approximation (GBHCT) and two different force fields: AMBER ff99 and
      a modified version of the latter described by Sorin and Pande (Biophys J 2005,
      88, 2472-2493), ff99SP. Comparison of the structures obtained from the MD
      trajectories and those derived from the NMR studies in the literature indicates
      that the GBOBC method is more efficient in the exploration of the conformational
      space and presents a higher agreement with the experimental structure of VIP and
      PACAP27 in TFE.

PMID- 19156831
TI  - Toxicity and survival outcomes of hyperfractionated split-course reirradiation
      and daily concurrent chemotherapy in locoregionally recurrent, previously
      irradiated head and neck cancers.
AB  - BACKGROUND: : Reirradiation of locoregionally recurrent, previously irradiated
      head/neck cancer may be considered in situations of unresectability, medical
      inoperability, or adverse pathologic features found at salvage resection.
      METHODS: : Retrospective cohort analysis of toxicity and survival outcomes in
      locoregionally recurrent, previously irradiated patients with head/neck cancer
      treated with hyperfractionated split-course radiotherapy and concurrent
      chemotherapy. RESULTS: : Between March 1998 and September 2006, 39 patients
      initiated reirradiation at median of 2.3 years (range, 0.5-19) following prior
      radiotherapy. At median survivor follow-up of 24.5 months (range, 3-63.9), 10
      patients are alive without evidence of disease. Median survival is 19.0 months,
      with estimated 1-, 2-, and 3-year overall survivals of 60.1%, 45.1%, and 22.7%,
      respectively. Locoregional failure was the predominant site of postreirradiation
      recurrence. Male sex, total radiotherapy dose, cycles of chemotherapy completed,
      and clinical response were associated with improved overall survival.
      CONCLUSIONS: : Reirradiation can offer long-term survival for patients with
      recurrent, previously irradiated head/neck cancers.

PMID- 19156832
TI  - Effect of autologous platelet adhesives on dermal fat graft resorption following
      reconstruction of a superficial parotidectomy defect: a double-blinded
      prospective trial.
AB  - BACKGROUND: Dermal fat grafts are used to reconstruct facial contour defects but
      may undergo variable resorption. Application of autologous platelet adhesive may
      improve outcomes. The primary objective was to compare resorption of dermal fat
      grafts for parotidectomy defects, between patients receiving autologous platelet
      adhesive versus controls. METHODS: This was a double-blinded prospective cohort
      at a tertiary care center. Volumetric analyses of dermal fat graft measured by
      MRI scans. Resorption was determined by comparing 1- and 6-month MRIs in each
      patient. Complications, Frey's Syndrome, and patient satisfaction were also
      assessed. RESULTS: Twelve patients completed the study. A significant reduction
      in graft resorption was seen in the treatment group (57% vs. 31%, p = .01). Three
      patients in the control group developed fat liquefaction. Patient perceived
      significant differences in scar and contour. CONCLUSION: Application of
      autologous platelet adhesives improved graft viability and patient satisfaction
      at 6 months.

PMID- 19156833
TI  - Function, postoperative morbidity, and quality of life after cervical sentinel
      node biopsy and after selective neck dissection.
AB  - BACKGROUND: Sentinel node biopsy (SNB) has been proposed for staging of N0 neck
      in oral/oropharyngeal carcinomas. It is claimed that SNB may be superior to
      selective neck dissection (SND) with respect to quality of life (QOL) and
      postoperative morbidity. METHODS: Twenty-four patients after SNB and 25 patients
      after SND (levels I-III) were enrolled. QOL and psychosocial variables were
      assessed by the health-related EORTC QLQ-C30 questionnaire, the disease-specific
      EORTC QLQ-H&N35 module, the Hospital Anxiety and Depression Scale, and a fear of
      progression questionnaire. The functional status was evaluated by scores for
      cervical scar, extent of lymphedema (Miller score), sensory function, function of
      facial and hypoglossal nerve, cervical spine, and shoulder (Constant score).
      RESULTS: Health-related QOL measurement revealed no differences between the 2
      groups. Disease-specific QOL scores showed fewer swallowing problems in SNB
      patients (p = .043). SNB patients felt less fear of progression, experienced
      significantly less impairment from cervical scars, and had less sensory
      dysfunction and better shoulder function. CONCLUSION: Functional outcome after
      SNB is significantly better than after SND; however, this is not reflected in the
      scores of QOL questionnaires.

PMID- 19156834
TI  - Role of chest CT in staging of oropharyngeal cancer: a systematic review.
AB  - BACKGROUND: The prevalence of synchronous or metastatic tumors in patients with
      head and neck squamous cell carcinoma (HNSCC) ranges from 6% to 20% and has
      implications for prognosis and management of the primary disease. There is no
      consensus about the role of chest CT prior to definitive treatment patients with
      HNSCC. METHODS: A systematic review of all chest CT studies in relation to HNSCC
      was performed, together with a review of our local database. RESULTS: Twenty-four
      studies were identified in addition to our local data. Prevalence of positive
      chest CT was 7.93%. Patients were significantly more likely to have a positive
      chest CT with N2 or N3 neck disease (p = .0062) and stage III or IV disease (p =
      .0001), and significantly less likely with tumors of the oral cavity (p = .0007).
      CONCLUSION: We advocate chest CT as part of the initial investigations for
      patients with HNSCC.

PMID- 19156836
TI  - Loss of 16q in high grade breast cancer is associated with estrogen receptor
      status: Evidence for progression in tumors with a luminal phenotype?
AB  - Loss of the long arm of chromosome 16 (16q) is observed in the vast majority of
      low grade/grade I (GI) invasive ductal carcinomas of no special type (IDC-NSTs),
      whereas this event is uncommonly seen in high grade/grade III (GIII) IDC-NSTs.
      Together with data on the pathology and genetics of breast cancer recurrences,
      this has led to the proposal that GI and GIII breast cancers evolve through
      distinct genetic pathways and that progression from GI to GIII is an unlikely
      biological phenomenon. We compared the genomic profiles of GIII-IDC-NSTs with 16q
      whole arm loss (16qWL) according to estrogen receptor (ER) status. 16qWL was
      found in 36.5% of cases and was significantly associated with ER expression and
      luminal phenotype. ER+ GIII-IDC-NSTs with 16qWL displayed significantly higher
      levels of genomic instability than ER+ IDC-NSTs without 16qWL. Furthermore, ER+
      and ER- IDC-NSTs stratified according to the presence of 16qWL harbored distinct
      patterns of genetic aberrations. Interestingly, ER+/16qWL tumors displayed
      genetic features usually found in tumors with homologous DNA repair defects and
      significantly more frequently harbored heterozygous loss of BRCA2 than the
      remaining ER+ cancers. Our results demonstrate that approximately one third of
      GIII tumors harbor 16qWL, confirming that progression from low to high grade
      breast cancer is not found in the majority of breast cancers. 16qWL was
      significantly more prevalent in ER+/luminal GIII-IDC-NSTs. Given that GI breast
      cancers harbor a luminal phenotype, our results suggest that if progression from
      GI to GIII breast cancer does happen, it may preferentially occur in breast
      cancers of luminal phenotype.

PMID- 19156838
TI  - Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular
      dystrophy mutations.
AB  - Antisense-mediated exon skipping aiming for reading frame restoration is
      currently a promising therapeutic application for Duchenne muscular dystrophy
      (DMD). This approach is mutation specific, but as the majority of DMD patients
      have deletions that cluster in hotspot regions, the skipping of a small number of
      exons is applicable to relatively large numbers of patients. To assess the actual
      applicability of the exon skipping approach, we here determined for deletions,
      duplications and point mutations reported in the Leiden DMD mutation database,
      which exon(s) should be skipped to restore the open reading frame. In theory,
      single and double exon skipping would be applicable to 79% of deletions, 91% of
      small mutations, and 73% of duplications, amounting to 83% of all DMD mutations.
      Exon 51 skipping, which is being tested in clinical trials, would be applicable
      to the largest group (13%) of all DMD patients. Further research is needed to
      determine the functionality of different in-frame dystrophins and a number of
      hurdles has to be overcome before this approach can be applied clinically.

PMID- 19156839
TI  - Protein sequences encode safeguards against aggregation.
AB  - Functional requirements shaped proteins into globular structures. Under these
      structural constraints, which require both regular secondary structure and a
      hydrophobic core, protein aggregation is an unavoidable corollary to protein
      structure. However, as aggregation results in reduced fitness, natural selection
      will tend to eliminate strongly aggregating sequences. The analysis of
      distribution and variation of aggregation patterns in the human proteome using
      the TANGO algorithm confirms the findings of a previous study on several
      proteomes: the flanks of aggregation-prone regions are enriched with charged
      residues and proline, the so-called gatekeeper-residues. Moreover, in this study,
      we observed a widespread redundancy in gatekeeper usage. Interestingly,
      aggregating regions from key proteins such as p53 or huntingtin are among the
      most extensive "gatekept" sequences. As a consequence, mutations that remove
      gatekeepers could therefore result in a strong increase in disease
      susceptibility. In a set of disease-associated mutations from the UniProt
      database, we find a strong enrichment of mutations that disrupt gatekeeper
      motifs. Closer inspection of a number of case studies indicates clearly that
      removing gatekeepers may play a determining role in widely varying disorders,
      such as van der Woude syndrome (VWS), X-linked Fabry disease (FD), and limb
      girdle muscular dystrophy.

PMID- 19156837
TI  - Distinct genomic aberrations associated with ERG rearranged prostate cancer.
AB  - Emerging molecular and clinical data suggest that ETS fusion prostate cancer
      represents a distinct molecular subclass, driven most commonly by a hormonally
      regulated promoter and characterized by an aggressive natural history. The study
      of the genomic landscape of prostate cancer in the light of ETS fusion events is
      required to understand the foundation of this molecularly and clinically distinct
      subtype. We performed genome-wide profiling of 49 primary prostate cancers and
      identified 20 recurrent chromosomal copy number aberrations, mainly occurring as
      genomic losses. Co-occurring events included losses at 19q13.32 and 1p22.1. We
      discovered three genomic events associated with ERG rearranged prostate cancer,
      affecting 6q, 7q, and 16q. 6q loss in nonrearranged prostate cancer is
      accompanied by gene expression deregulation in an independent dataset and by
      protein deregulation of MYO6. To analyze copy number alterations within the ETS
      genes, we performed a comprehensive analysis of all 27 ETS genes and of the 3 Mbp
      genomic area between ERG and TMPRSS2 (21q) with an unprecedented resolution (30
      bp). We demonstrate that high-resolution tiling arrays can be used to pin-point
      breakpoints leading to fusion events. This study provides further support to
      define a distinct molecular subtype of prostate cancer based on the presence of
      ETS gene rearrangements.

PMID- 19156840
TI  - On the mechanism and dynamics of uptake and permeation of polyether-copolyester
      dendrimers across an in vitro blood-brain barrier model.
AB  - Dendrimers have emerged as a promising drug delivery system due to their well
      defined size, tailorability, and multifunctional nature. However, their
      application in brain delivery is relatively a new area of research. The present
      study was aimed at evaluating the uptake and permeation of polyether-copolyester
      (PEPE) dendrimers across the blood-brain barrier model and exploring the
      underlying mechanisms. Saturation was observed in the uptake of rhodamine B
      labeled PEPE dendrimers by brain vascular endothelial (bEnd.3) cells at high
      concentrations. Clathrin and caveolin inhibitors produced partial inhibition of
      the dendrimer uptake, signifying contribution of both pathways in the uptake
      process. PEPE dendrimers were able to cross in vitro BBB model in high amounts
      with P(app) of 19.7 +/- 1.9 x 10(-6) cm/s and 38.6 +/- 4.1 x 10(-6) cm/s for den
      1-(G2)-400 and den-2-(G2)-400, respectively; and only 11-14% reduction in
      transendothelial electrical resistance during initial 4 h. The results of this
      study suggest that architecture of dendrimers plays a major role not only in
      influencing the extent and mechanism of uptake by bEnd.3 cells but also
      permeation across the BBB model. =

PMID- 19156841
TI  - Haplotypes of the NR4A2/NURR1 gene and cardiovascular disease: the Rotterdam
      Study.
AB  - Nuclear receptor subfamily 4, group A, member 2 (NR4A2, also called Nurr1) has
      lately become of interest with regard to atherogenesis. We examined the
      association between common variation in the NR4A2 gene and cardiovascular disease
      in the Rotterdam Study, a prospective population-based study among persons aged >
      or = 55 years. Three SNPs that tag common haplotypes across a 36-kb region
      surrounding the NR4A2 gene were determined. Four haplotypes with frequencies >1%
      covered 96% of the genetic variation. In 5,650 participants without history of
      coronary heart disease, 729 coronary heart disease events occurred during a
      median follow-up time of 11.9 years. NR4A2 haplotypes were neither associated
      with coronary events nor with intima-media thickness (IMT), carotid plaques, or
      ankle-arm index (AAI). NR4A2 haplotypes showed a tendency toward associations
      with aortic and coronary calcification (haplo.score global simulation P values
      0.076 and 0.075, respectively), which seemed to be based on haplotype 2
      (individual P values were both P=0.015). Furthermore, NR4A2 haplotype 3 was
      associated with higher high-density lipoprotein (HDL) cholesterol and haplotype 4
      with lower systolic blood pressure. In conclusion, NR4A2/NURR1 haplotypes were
      not associated with coronary events, carotid IMT, carotid plaques, or AAI. There
      was a tendency toward associations with aortic calcification and coronary
      calcification. Associations for NR4A2 were found with both HDL levels and blood
      pressure. It remains to be investigated which pathophysiological mechanisms
      pertain to NR4A2 function in cardiovascular disease.

PMID- 19156842
TI  - Combining the interactome and deleterious SNP predictions to improve disease gene
      identification.
AB  - A method has been developed for the prediction of proteins involved in genetic
      disorders. This involved combining deleterious SNP prediction with a system based
      on protein interactions and phenotype distances; this is the first time that
      deleterious SNP prediction has been used to make predictions across linkage
      intervals. At each step we tested and selected the best procedure, revealing that
      the computationally expensive method of assigning medical meta-terms to create a
      phenotype distance matrix was outperformed by a simple word counting technique.
      We carried out in-depth benchmarking with increasingly stringent data sets,
      reaching precision values of up to 75% (19% recall) for 10-Mb linkage-intervals
      (averaging 100 genes). For the most stringent (worst-case) data we attained an
      overall recall of 6%, yet still achieved precision values of up to 90% (4%
      recall). At all levels of stringency and precision the addition of predicted
      deleterious SNPs was shown to increase recall.

PMID- 19156843
TI  - Hepatic metabolism and biliary excretion of valerenic acid in isolated perfused
      rat livers: role of Mrp2 (Abcc2).
AB  - The study was designed to investigate the hepatic metabolism and transport system
      of valerenic acid, a main active constituent of valerian, in isolated perfused
      livers from Wistar and Mrp2-deficient TR(-) rats. After administration of 20
      microM valerenic acid, the formation of seven valerenic acid glucuronides (M1
      M7), namely two glucuronides of valerenic acid (M6, M7), four glucuronides of
      hydroxylated valerenic acid (M1, M3, M4, M5), and one glucuronide of hydroxylated
      dehydro-valerenic acid (M2) in bile and perfusate was quantified by HPLC. The
      hepatic extraction ratio and clearance of valerenic acid were very high in Wistar
      and TR(-) rats (E: 0.983 +/- 0.006 vs. 0.981 +/- 0.004; Cl: 35.4 +/- 0.21 mL/min
      vs. 35.3 +/- 0.14 mL/min). However, biliary excretion and efflux of conjugates
      differed greatly in TR(-) rats. While cumulative biliary excretion of
      unconjugated valerenic acid and the glucuronides M1-M7 dropped dramatically to 1
      9%, their efflux into perfusate increased 1.5- to 10-fold. This indicates that
      valerenic acid and its glucuronides are eliminated into bile by Mrp2. In summary,
      valerenic acid was metabolized to several conjugates, whereby the canalicular
      transporter Mrp2 mediated biliary excretion of the parent drug and its
      glucuronides.

PMID- 19156844
TI  - Enzymatically catalyzed HES conjugation using microbial transglutaminase: Proof
      of feasibility.
AB  - Polymer-drug and polymer-protein conjugates are promising candidates for the
      delivery of therapeutic agents. PEGylation, using poly(ethylene glycol) for the
      conjugation, is now the gold standard in this field, and some PEGylated proteins
      have successfully reached the market. Hydroxyethyl starch (HES) is a water
      soluble, biodegradable derivative of starch that is currently being investigated
      as a substitute for PEG. So far, only chemical methods have been suggested for
      HES conjugation; however, these may have detrimental effects on proteins. Here,
      we report an enzymatic method for HES conjugation using a recombinant microbial
      transglutaminase (rMTG). The latter catalyzes the acyl transfer between the gamma
      carboxamide group of a glutaminyl residue (acyl donors) and a variety of primary
      amines (acyl acceptors), including the amino group of lysine. HES was modified
      with N-carbobenzyloxy glutaminyl glycine (Z-QG) and hexamethylene diamine (HMDA)
      to act as acyl donor and acyl acceptor, respectively. Using (1)H NMR, the degree
      of modification with Z-QG and HMDA was found to be 4.6 and 3.9 mol%,
      respectively. Using SDS-PAGE, it was possible to show that the modified HES
      successfully coupled to test compounds, proving that it is accepted as a
      substrate by rMTG. Finally, the process described in this study is a simple, mild
      approach to produce fully biodegradable polymer-drug and polymer-protein
      conjugates.

PMID- 19156845
TI  - Effects of oxygen-containing terpenes as skin permeation enhancers on the
      lipoidal pathways of human epidermal membrane.
AB  - The present study investigated the effects of oxygen-containing terpenes as skin
      permeation enhancers on the lipoidal pathways of human epidermal membrane (HEM).
      The enhancement (E(HEM)) effects of menthol, thymol, carvacrol, menthone, and
      cineole on the transport of a probe permeant, corticosterone, across HEM were
      determined. It was found that the enhancer potencies of menthol, thymol,
      carvacrol, and menthone were essentially the same and higher than that of cineole
      based on their aqueous concentration in the diffusion cell chamber at E(HEM) = 4.
      Thymol and carvacrol also had the same E(HEM) = 10 concentration further
      supporting that they had the same enhancer potency based on the aqueous
      concentration. The uptake amounts of terpene into the HEM stratum corneum (SC)
      intercellular lipid under the same conditions indicate that the intrinsic
      potencies of the studied terpenes are the same based on their concentration in
      the SC and similar to those of n-alkanol and n-alkylphenyl alcohol. Moreover,
      they are all better enhancers compared to branched-chain alkanol. The
      approximately same uptake enhancement of beta-estradiol induced by the studied
      terpenes and alcohols at E(HEM) conditions into the SC intercellular lipids
      suggests that the mechanism of enhancement action for the terpenes and those of
      alcohols are essentially the same.

PMID- 19156846
TI  - Sugar fuels cancer.

PMID- 19156848
TI  - Changes in hippocampal morphology and neuroplasticity induced by adolescent THC
      treatment are associated with cognitive impairment in adulthood.
AB  - Marijuana and hashish are the illicit drugs most frequently used by human
      adolescents. Given the continued neurodevelopment throughout adolescence,
      adolescents may be more vulnerable than adults to certain neural consequences of
      heavy marijuana use. This study aimed to assess whether an experimental model of
      adolescent chronic exposure to Delta9-tetrahydrocannabinol (THC), may induce
      lasting effects on learning and memory. Adolescent rats have been treated with
      THC or its vehicle from 35 to 45 postnatal days (PND) and left undisturbed until
      their adulthood (75 PND) when aversive and spatial memory was assessed using the
      passive avoidance and radial maze tasks. No alteration was found in aversive
      memory, but in the radial maze THC pretreated animals exhibited a worse
      performance than vehicles, suggesting a deficit in spatial working memory. To
      correlate memory impairment to altered neuroplasticity, level of marker proteins
      was investigated in the hippocampus, the most relevant area mediating spatial
      memory. A significant decrease in the astroglial marker glial fibrillar acid
      protein was found as well as in pre- and postsynaptic protein expression (VAMP2,
      PSD95) and NMDA receptor levels in pretreated rats. To parallel these changes to
      alteration in dendritic morphology, Golgi-Cox staining was performed in the
      hippocampal dentate gyrus. Pretreated rats had a significantly lower total
      dendritic length and number than vehicles, as well as reduced spine density. Our
      data suggest that THC pretreated rats may establish less synaptic contacts and/or
      less efficient synaptic connections throughout the hippocampus and this could
      represent the molecular underpinning of the cognitive deficit induced by
      adolescent THC treatment.

PMID- 19156849
TI  - A molecular blueprint of gene expression in hippocampal subregions CA1, CA3, and
      DG is conserved in the brain of the common marmoset.
AB  - Recent studies in rodents have shown that there are significant differences in
      gene expression profiles between the hippocampal subregions CA1, CA3, and DG.
      These differences in molecular make-up within the hippocampus most likely
      underlie the differences in morphology, physiology, and vulnerability to insults
      that exist between the subregions of the hippocampus and are as such part of the
      basic molecular architecture of the hippocampus. The aim of this study was to
      investigate at large scale whether these subregional differences in gene
      expression are conserved in the hippocampus of a nonhuman primate, the common
      marmoset. This study is very timely, given the recent development of the first
      marmoset-specific DNA microarray, exclusively containing sequences targeting
      transcripts derived from the marmoset hippocampus. Hippocampal subregions CA1,
      CA3, and DG were isolated by laser microdissection and RNA was isolated,
      amplified, and hybridized to the marmoset-specific microarray (EUMAMA) containing
      more than 1,500 transcripts expressed in the adult marmoset hippocampus. Large
      differences in expression were observed in particular between the DG region and
      both pyramidal subregions. Moreover, the subregion-specific patterns of gene
      expression showed a remarkable conservation with the rodent brain both in terms
      of individual genes and degree of differential expression. To our knowledge, this
      is the first study investigating large scale hippocampal gene expression in a
      nonhuman primate. The obtained expression profiles not only provide novel data on
      the expression of more than 1,500 transcripts per hippocampal subregion but also
      are of potential interest to neuroscientists interested in the role of the
      different subregions in learning and memory in the nonhuman primate brain.

PMID- 19156850
TI  - A case of natural killer cell lymphoma presenting with bilateral pleural
      effusions and hemophagocytic lymphohistocytosis.
AB  - Natural killer (NK) cell lymphoma of lung is very rare. We report a case of NK
      cell lymphoma presented in a 17-year-old male with bilateral pleural effusions
      and hemophagocytic lymphohistocytosis. Morphologic and immunohistochemical tests
      revealed an association of NK cell lymphoma with Epstein-Barr virus. A literature
      review helped identify other cases of patients with NK cell lymphoma, their
      treatment and outcomes.

PMID- 19156851
TI  - Cholesterol-promoted synaptogenesis requires the conversion of cholesterol to
      estradiol in the hippocampus.
AB  - Cholesterol of glial origin promotes synaptogenesis (Mauch et al., (2001) Science
      294:1354-1357). Because in the hippocampus local estradiol synthesis is essential
      for synaptogenesis, we addressed the question of whether cholesterol-promoted
      synapse formation results from the function of cholesterol as a precursor of
      estradiol synthesis in this brain area. To this end, we treated hippocampal
      cultures with cholesterol, estradiol, or with letrozole, a potent aromatase
      inhibitor. Cholesterol increased neuronal estradiol release into the medium, the
      number of spine synapses in hippocampal slice cultures, and immunoreactivity of
      synaptic proteins in dispersed cultures. Simultaneous application of cholesterol
      and letrozole or blockade of estrogen receptors by ICI 182 780 abolished
      cholesterol-induced synapse formation. As a further approach, we inhibited the
      access of cholesterol to the first enzyme of steroidogenesis by knock-down of
      steroidogenic acute regulatory protein, the rate-limiting step in
      steroidogenesis. A rescue of reduced synaptic protein expression in transfected
      cells was achieved by estradiol but not by cholesterol. Our data indicate that in
      the hippocampus cholesterol-promoted synapse formation requires the conversion of
      cholesterol to estradiol.

PMID- 19156852
TI  - Reduced excitability in the dentate gyrus network of betaIV-spectrin mutant mice
      in vivo.
AB  - The submembrane cytoskeletal meshwork of the axon contains the scaffolding
      protein betaIV-spectrin. It provides mechanical support for the axon and anchors
      membrane proteins. Quivering (qv(3j)) mice lack functional betaIV-spectrin and
      have reduced voltage-gated sodium channel (VGSC) immunoreactivity at the axon
      initial segment and nodes of Ranvier. Because VGSCs are critically involved in
      action potential generation and conduction, we hypothesized that qv(3j) mice
      should also show functional deficits at the network level. To test this
      hypothesis, we investigated granule cell function in the dentate gyrus of
      anesthetized qv(3j) mice after electrical stimulation of the perforant path in
      vivo. This revealed an impaired input-output relationship between stimulus
      intensity and granule cell population spikes and an enhanced paired-pulse
      inhibition of population spikes, indicating a reduced ability of granule cells to
      generate action potentials and decreased network excitability. In contrast, the
      input-output curve for evoked field excitatory postsynaptic potentials (fEPSPs)
      and paired-pulse facilitation of fEPSPs were unchanged, suggesting normal
      excitatory synaptic transmission at perforant path-granule cell synapses in
      qv(3j) mutants. To corroborate our findings, we analyzed the influence of VGSC
      density reduction on dentate network activity using an established computational
      model of the dentate gyrus network. This in silico approach confirmed that the
      loss of VGSCs is sufficient to explain the electrophysiological changes observed
      in qv(3j) mice. Taken together, our findings demonstrate that betaIV-spectrin is
      required for normal granule cell firing and for physiological levels of network
      excitability in the mouse dentate gyrus in vivo.

PMID- 19156853
TI  - Synaptic potentiation induces increased glial coverage of excitatory synapses in
      CA1 hippocampus.
AB  - Patterns of activity that induce synaptic plasticity at excitatory synapses, such
      as long-term potentiation, result in structural remodeling of the postsynaptic
      spine, comprising an enlargement of the spine head and reorganization of the
      postsynaptic density (PSD). Furthermore, spine synapses represent complex
      functional units in which interaction between the presynaptic varicosity and the
      postsynaptic spine is also modulated by surrounding astroglial processes. To
      investigate how activity patterns could affect the morphological interplay
      between these three partners, we used an electron microscopic (EM) approach and
      3D reconstructions of excitatory synapses to study the activity-related
      morphological changes underlying induction of synaptic potentiation by theta
      burst stimulation or brief oxygen/glucose deprivation episodes in hippocampal
      organotypic slice cultures. EM analyses demonstrated that the typical glia
      synapse organization described in in vivo rat hippocampus is perfectly preserved
      and comparable in organotypic slice cultures. Three-dimensional reconstructions
      of synapses, classified as simple or complex depending upon PSD organization,
      showed significant changes following induction of synaptic potentiation using
      both protocols. The spine head volume and the area of the PSD significantly
      enlarged 30 min and 1 h after stimulation, particularly in large synapses with
      complex PSD, an effect that was associated with a concomitant enlargement of
      presynaptic terminals. Furthermore, synaptic activity induced a pronounced
      increase of the glial coverage of both pre- and postsynaptic structures, these
      changes being prevented by application of the NMDA receptor antagonist D-2-amino
      5-phosphonopentanoic acid. These data reveal dynamic, activity-dependent
      interactions between glial processes and pre- and postsynaptic partners and
      suggest that glia can participate in activity-induced structural synapse
      remodeling.

PMID- 19156855
TI  - Allogeneic hematopoietic stem cell transplantation of patients with FA and high
      risk features using fludarabine without radiation.
AB  - Several factors unique to Fanconi anemia (FA) limit the success of allogeneic
      hematopoietic stem cell transplantation (HSCT) in this population. In this
      report, we describe a multi-center pilot study of five consecutive FA patients
      with high-risk features for transplant prepared with fludarabine, without
      radiation. Four patients engrafted quickly, experienced minimal toxicity and are
      well at 43-65 months post-transplant. One patient had a C-mismatched unrelated
      donor transplant and had unsustained engraftment. This fludarabine based regimen
      without radiation was safe and effective for four high-risk patients, suggesting
      that eliminating radiation should be further studied as an approach to HSCT in
      children with FA.

PMID- 19156854
TI  - The effects of exercise and stress on the survival and maturation of adult
      generated granule cells.
AB  - Stress strongly inhibits proliferation of granule cell precursors in the adult
      dentate gyrus, whereas voluntary running has the opposite effect. Few studies,
      however, have examined the possible effects of these environmental manipulations
      on the maturation and survival of young granule cells. We examined the number of
      surviving granule cells and the proportion of young neurons that were
      functionally mature, as defined by seizure-induced immediate-early gene (IEG)
      expression, in 14- and 21-day-old granule cells in mice that were given access to
      a running wheel, restrained daily for 2 h, or given no treatment during this
      period. Treatments began 2 days after BrdU injection, to isolate effects on
      survival from those on cell proliferation. We found a large increase in granule
      cell survival in running mice when compared with controls at both time points. In
      addition, running increased the proportion of granule cells expressing the IEG
      Arc in response to seizures, suggesting that it speeds incorporation into
      circuits, i.e., functional maturation. Stressed mice showed no change in Arc
      expression, compared with control animals, but, surprisingly, showed a transient
      increase in survival of 14-day-old granule cells, which was gone 7 days later.
      Examination of cell proliferation, using the endogenous mitotic marker PCNA
      showed an increase in cell proliferation after 12 days of running but not after
      19 days of running. The number of proliferating cells was unchanged 24 h after
      the 12th or 19th episode of daily restraint stress. These findings demonstrate
      that running has strong effects on survival and maturation of young granule cells
      as well as their birth and that stress can have positive but short-lived effects
      on granule cell survival. Published 2009 Wiley-Liss, Inc.

PMID- 19156856
TI  - Predictors of non-participation in a randomized intervention trial to reduce
      environmental tobacco smoke (ETS) exposure in pediatric cancer patients.
AB  - BACKGROUND: Exposure to environmental tobacco smoke (ETS) is associated with the
      development of serious health consequences in children with cancer due to
      preexisting disease and treatment-related vulnerabilities. The purpose of the
      current investigation was to identify predictors of non-participation in a
      randomized intervention trial to reduce ETS exposure among pediatric cancer
      patients. METHODS: One hundred fifty-three families of pediatric cancer patients
      met study eligibility criteria. Parents of 117 (76%) patients agreed to study
      participation, whereas 36 (24%) parents declined (non-participants). Data were
      collected with respect to participant sociodemographic, medical, and treatment
      related characteristics. RESULTS: Univariate analyses indicated that families
      whose primary caregivers were females or smokers were more likely to be non
      participants in the ETS reduction trial (P = 0.045 and P = 0.009, respectively).
      Medical features that significantly associated with study non-participation
      included CNS tumor diagnosis (P = 0.030), no history of chemotherapy (P = 0.012),
      history of surgery prior to study recruitment (P = 0.036), and having future
      radiation therapy planned post study recruitment (P = 0.009). Multivariable
      logistic regression modeling revealed that study non-participation was associated
      with the primary caregiver being a smoker (OR = 6.48, P = 0.002) or female (OR =
      8.56, P = 0.023), and patient CNS tumor diagnosis (OR = 4.63, P = 0.021).
      CONCLUSIONS: Although a large percentage of eligible participants enrolled in the
      ETS reduction trial, findings suggest that future recruitment strategies of
      families should be tailored to parental smoking status and gender, as well as
      child diagnosis and treatment.

PMID- 19156857
TI  - Sialoblastoma and hepatoblastoma in a newborn infant.
AB  - We report a case of a newborn infant who had simultaneous sialoblastoma and
      hepatoblastoma tumours at birth. The diagnoses were made on post mortem
      examination. Both of these are rare tumours in the neonatal period.

PMID- 19156858
TI  - Differentiated P19 cells express N-methyl-D-aspartate receptor 1 mRNA binding
      trans-acting proteins and four N-methyl-D-aspartate receptor 1 splice variants
      comparable to those in cultured fetal cortical neurons.
AB  - Differentiated P19 cells naturally express N-methyl-D-aspartate (NMDA) receptors
      and serve as a good in vitro model system with which to study NMDA receptor
      regulation. Here we examined expression of NR1 mRNA binding trans-acting proteins
      and NR1 splice variants in P19 cells. After exposure to retinoic acid, P19 cells
      were differentiated for 2, 4, 6, and 8 days in vitro (DIV). Total RNA and protein
      extracts from differentiated P19 cells were utilized to examine NR1 and NR2B
      expression. A steady increase in NR1 and NR2B mRNA and protein levels was
      observed with respect to days of differentiation. NR2B mRNA was detected within 2
      DIV. However, NR2B protein appeared only at 4 DIV. By contrast, minimal
      expression of NR1 mRNA could be detected in undifferentiated P19 cells, whereas
      NR1 protein was detected at 4 DIV. RT-PCR analysis identified expression of four
      of eight full-length NR1 splice variants, similar to the expression pattern seen
      in fetal cortical neurons (FCN). These data were confirmed by ribonuclease
      protection assays. RNA gel shift assays and Northwestern analysis revealed the
      expression of NR1 mRNA binding trans-acting proteins in P19 neurons comparable to
      those expressed in FCN. RNA super gel shift assays confirmed the presence of the
      NR1 mRNA binding trans-acting protein GIIbeta in the NR1-3'UTR-P19 protein
      complex. Levels of GIIbeta polypeptide increased with increase in days of
      differentiation. Taken together, our data demonstrate that differentiated P19
      cells are comparable to FCN and hence provide an excellent in vitro model for
      studying NR1 mRNA regulation at the posttranscriptional level.

PMID- 19156859
TI  - HIF prolyl hydroxylase inhibition augments dopamine release in the rat brain in
      vivo.
AB  - The transcription factor hypoxia-inducible factor (HIF) is essential for the
      activation of several genes that promote the survival of cells exposed to
      oxidative stress. Expression of tyrosine hydroxylase (TH), which is the rate
      limiting enzyme in the dopamine (DA) synthesis, is one of the genes that are
      positively regulated by HIF. Accordingly, HIF induction results in elevated DA
      release in various cell lines in vitro. HIF prolyl hydroxylase (HPH) is
      critically involved in the negative regulation of HIF levels. We investigated the
      in vivo effects of the HPH inhibitor FG0041 on brain DA function in rats by
      microdialysis in freely moving rats, locomotor activity, and Western blot
      analysis. Administration of FG0041 (10 mg/kg i.p.), as an acute (single
      injection), or as subchronic (once daily for 6 days) treatment and cobalt
      chloride (CoCl2) (60 mg/kg s.c.) potentiated potassium (K+) induced increases in
      extracellular levels of DA levels in the rat striatum. The increase in
      extracellular DA of freely moving rats was sought in relationship to locomotor
      activity in rats. A significant increase in locomotor activity was observed in
      FG0041-treated rats compared with vehicle on a cocaine challenge. In support of
      these findings, protein levels of TH in the rat brain stem were increased after
      treatment with FG0041. These data indicate that FG0041 augments DA function in
      the rat brain. Inhibition of HPH enhances DA function by increasing DA release,
      which has implications for the use of HIF induction in the treatment of
      neurodegenerative diseases.

PMID- 19156861
TI  - Bed nucleus of the stria terminalis N-methyl-D-aspartate receptors and nitric
      oxide modulate the baroreflex cardiac component in unanesthetized rats.
AB  - The bed nucleus of the stria terminalis (BST) plays a tonic role modulating the
      baroreflex bradycardiac response. In the present study, we verified whether local
      BST glutamatergic receptors and nitric oxide (NO) system modulate baroreflex
      bradycardiac responses. Bilateral BST- N-methyl-D-aspartate (NMDA) receptor
      inhibition by treatment with the selective NMDA receptor antagonist LY235959
      increased bradycardiac response to mean arterial pressure increases. Treatment
      with the selective non-NMDA antagonist NBQX did not affect reflex bradycardia.
      These results suggest an involvement of local NMDA receptors in the BST-related
      tonic inhibitory modulation of baroreflex bradycardiac response. BST treatment
      with the nonselective NO synthase (NOS) inhibitor L-NAME or the selective
      neuronal NOS (nNOS) inhibitor N(omega)-propyl-L-arginine increased bradycardiac
      response, indicating that NO generated by nNOS activation modulates baroreflex.
      The NO involvement was further reinforced by observation that BST treatment with
      the NO scavenger carboxy-PTIO caused an effect similar to that observed after
      NMDA receptor blockade or treatment with NOS inhibitors. Additionally, it was
      observed that LY235959 effects on baroreflex bradycardiac response were reverted
      by BST treatment with the NO-donor sodium nitroprusside, suggesting an NMDA
      receptor-NO interaction. Baroreflex bradycardiac responses observed before and
      after BST treatment with LY235959 or N(omega)-propyl-L-arginine were no longer
      different when animals were pretreated intravenously with the anticholinergic
      drug homatropine methyl bromide. These results indicate that parasympathetic
      activation accounts for the effects observed after BST pharmacological
      manipulation. In conclusion, our data point out that local NMDA and nNOS
      interaction mediates the tonic inhibitory influence of the BST on the baroreflex
      bradycardiac response, modulating the parasympathetic cardiac activity.

PMID- 19156862
TI  - Retrospective analysis of relapsed or primary refractory childhood lymphoblastic
      lymphoma in Japan.
AB  - BACKGROUND AND PROCEDURE: To assess the clinical course with response to second
      line treatment and to evaluate the role of hematopoietic stem cell
      transplantation (SCT) in children with relapsed or primary refractory
      lymphoblastic lymphoma (LBL), we analyzed data of 48 patients with
      relapsed/primary refractory diseases among 260 LBL patients identified in a
      national survey of 1996-2004. RESULTS: Twenty-six patients achieved second
      complete remission; 9 achieved partial remission. Of 13 patients who showed
      progression despite first and second line therapy, only one patient was alive on
      the second relapse after unrelated cord blood transplantation. Among 40 relapsed
      patients, the median time between initial diagnosis and relapse was 12.5 months
      (range 3-56 months). The sites of relapse were isolated BM (n = 9), primary local
      site with BM (9), primary local site (6), isolated CNS (4), local site with
      mediastinum (4), primary local site with other site (4), and others (4). Of all
      48 patients, 3 were alive after chemotherapy alone. Of the 33 patients, 14 were
      alive after high dose chemotherapy (HDC)/SCT. With a 27.5-month median follow up
      period, the 3-year OS rate was 43.2 +/- 7.4% (estimate +/- SE). Univariate
      analysis identified two features (relapse within 12 months, T cell phenotype) as
      significant variables that predicted poor survival. Multivariate analysis showed
      novel statistically significant variables including relapse within 12 months from
      initial diagnosis (Hazard ratio 3.60) and absence of HDC/SCT (2.64). CONCLUSION:
      Outcomes of patients with relapsed/primary refractory LBL were poor, but HDC/SCT
      for these patients was associated with good results.

PMID- 19156860
TI  - Proteomic analysis of optic nerve lipid rafts reveals new paranodal proteins.
AB  - Neuron-glia interactions at paranodal junctions play important roles in action
      potential propagation. Among their many functions, they contribute to the passive
      electrical properties of myelinated nerve fibers and actively regulate the
      polarized distribution of ion channels along axons. Despite their importance,
      relatively little is known about the molecules responsible for paranode formation
      and function. Paranodal junction formation apparently depends on interactions
      among three cell adhesion molecules: caspr and contactin on the axon and
      neurofascin 155 (NF-155) on the glial membrane. Using Caspr-null paranodal mutant
      mice, we demonstrate that loss of paranodal junctions causes failure of NF-155 to
      partition into lipid rafts, indicating that proteins located at paranodal
      junctions have biochemical characteristics of lipid raft-associated proteins.
      Based on this property of paranodal junctions, mass spectrometry of lipid rafts
      isolated from a pure white matter tract (optic nerve) was used to search for new
      paranodal proteins. Because we used a relatively crude biochemical preparation,
      we identified several hundred different proteins. Among these, we found all
      previously described paranodal proteins. Further analysis based on antibody
      staining of central and peripheral nerves revealed beta-adducin, septin 2, and
      sh3p8 as putative paranodal proteins. We describe the localization of these
      proteins in relation to other markers of nodes, paranodes, and juxtaparanodes in
      adult and developing nerve fibers. Finally, we describe their distribution in
      dysmyelinating TremblerJ mice, a model for the peripheral neuropathy Charcot
      Marie-Tooth disease.

PMID- 19156863
TI  - The changing face of PTSD diagnosis.

PMID- 19156864
TI  - Immunoadsorption with tryptophan columns: a therapeutic option for the treatment
      of rheumatoid arthritis with septic complications.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting
      multiple organs and tissues. Although there is a wide range of therapeutic
      applications, the coexistence of severe side effects and contraindications
      outlines the necessity of new therapeutic options in the treatment of severe RA.
      We report on the case of a 71-year-old patient with successful treatment of a
      complicated RA with tryptophan immunoadsorption combined with low-dose steroids.
      Bacterial spondylitis developed in this patient during long-term treatment with
      infliximab and methotrexate. Weekly immunoadsorption sessions with tryptophan
      columns resulted in continuous suppression of RA activity over a period of more
      than 5 months, as indicated by laboratory findings, the disease activity score,
      and the visual analog scale. This is the first report of successful treatment of
      a refractory and complicated RA using tryptophan immunoadsorption columns. In
      conclusion, immunoadsorption is a safe and effective therapeutic alternative,
      which should be considered to bridge infectious complications in patients with
      severe RA.

PMID- 19156865
TI  - Structural characterisation and dehydration behaviour of siramesine
      hydrochloride.
AB  - In this study the crystal structures of siramesine hydrochloride anhydrate alpha
      form and siramesine hydrochloride monohydrate were determined, and this
      structural information was used to explain the physicochemical properties of the
      two solid forms. In the crystal structure of the monohydrate, each water molecule
      is hydrogen bonded to two chloride ions, and thus the water is relatively
      strongly bound in the crystal. No apparent channels for dehydration were observed
      in the monohydrate structure, which could allow transmission of structural
      information during dehydration. Instead destructive dehydration occurred, where
      the elimination of water from the monohydrate resulted in the formation of an
      oily phase, which subsequently recrystallised into one or more crystalline forms.
      Solubility and intrinsic dissolution rate of the anhydrate alpha-form and the
      monohydrate in aqueous media were investigated and both were found to be lower
      for the monohydrate compared to the anhydrate alpha-form. Finally, the
      interactions between water molecules and chloride ions in the monohydrate as well
      as changes in packing induced by water incorporation could be detected by
      spectroscopic techniques.

PMID- 19156866
TI  - All-trans retinoic acid inhibits cobalt chloride-induced apoptosis in PC12 cells:
      role of the dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine
      pathway.
AB  - Previous studies have shown that the endogenous nitric oxide synthase inhibitor
      asymmetric dimethylarginine (ADMA) and its specific hydrolase dimethylarginine
      dimethylaminohydrolase (DDAH) are involved in the regulation of apoptosis in
      different cell types. In the present study, we investigated the role of the
      DDAH/ADMA pathway in cobalt chloride (CoCl(2))-induced apoptosis and the
      antiapoptotic effect of all-trans retinoic acid (atRA) in undifferentiated
      pheochromocytoma (PC12) cells. Treatment of CoCl(2) (125 microM) for 48 hr
      significantly induced the apoptosis of PC12 cells, concomitantly with increased
      intracellular reactive oxygen species (ROS) production and caspase-3 activity.
      CoCl(2) treatment also decreased the activity of DDAH and the expression of DDAH2
      (mRNA and protein), resulting in an increased level of ADMA. All these
      alterations induced by CoCl(2) were attenuated by atRA (0.1, 1, or 10 microM).
      Interestingly, the antiapoptotic effects of atRA were inhibited by DDAH2 small
      RNA interference. In contrast, DDAH2 overexpression inhibited the proapoptotic
      effects of CoCl(2). We also found that treatment of exogenous ADMA (3, 10, or 30
      microM) induced the apoptosis of PC12 cells in a concentration- and time
      dependent manner, which was inhibited by the antioxidant or the caspase-3
      inhibitor. These findings suggest that the modulation of the DDAH/ADMA/ROS
      pathway plays an important role in CoCl(2)-induced apoptosis and the
      antiapoptotic effects of atRA in undifferentiated PC12 cells.

PMID- 19156867
TI  - Regulation of dendrite growth by the Cdc42 activator Zizimin1/Dock9 in
      hippocampal neurons.
AB  - Rho family small GTPases are key regulators of morphological changes in neurons.
      Cdc42, one of the most characterized members of the Rho family of proteins, is
      involved in axon and dendrite outgrowth through cytoskeletal reorganization.
      Recent studies have identified Zizimin1, a member of the Dock180-related family
      of proteins [also called CDM (Ced-5/Dock180/Myoblast city)-zizimin homology (CZH)
      proteins], as a specific guanine-nucleotide exchange factor (GEF) for Cdc42.
      However, the physiological function of Zizimin1 is totally unknown. In this
      study, we investigated the role of Zizimin1 in dendrite development in rat
      hippocampal neurons. In situ hybridization and Western blot analysis showed that
      Zizimin1 is strongly expressed in the developing brain including in the
      hippocampus and cerebral cortex in late developmental stages. Overexpression of
      wild-type Zizimin1 promoted dendrite growth, whereas knockdown of Zizimin1 by
      short hairpin RNA or expression of a mutant Zizimin1 lacking Cdc42 GEF activity
      suppressed dendrite growth in primary cultured rat hippocampal neurons. Both the
      N-terminal CZH1 domain, which is conserved among CZH proteins, and the Pleckstrin
      homology domain of Zizimin1 are involved in membrane localization, Cdc42
      activation, and regulation of dendrite growth. Thus, these results suggest that
      Zizimin1 plays an important role in dendrite growth in hippocampal neurons
      through activation of Cdc42.

PMID- 19156868
TI  - Phosphothioated oligodeoxynucleotides induce nonspecific effects on neuronal cell
      adhesion in a growth substrate-dependent manner.
AB  - Synthetic phosphothioated (PTO) oligodeoxynucleotide (ODN) sequences are commonly
      used for a variety of applications that benefit from nuclease protection. The PTO
      modification is implemented mainly in antisense ODN, but also in ODN that were
      shown to activate members of the toll-like receptor (TLR) family such as TLR3
      (poly-I:C), TLR8 (ssRNA), and TLR9 (CpG). Neurons are routinely plated on
      surfaces coated with either cationic substances such as poly-L-ornithine (PLO),
      polyethylenimine (PEI), poly-L-lysine or ECM components such as laminin,
      collagen, or fibronectin. We found that PTO-ODN aimed at activating TLR9 induces
      a non-TLR9-specific detachment phenotype in cortical neurons plated on either
      laminin or PEI, but not on PLO. This phenotype was correlated with decreased
      viability and was partially inhibited when caspase-3 was inhibited with Ac-DEVD
      CMK. This finding suggests that the use of PTO-ODN can cause nonspecific effects
      on cell adhesion that could compromise interpretation of data from experiments
      using PTO-ODN.

PMID- 19156869
TI  - p75 NTR expression is induced in isolated neurons of the penumbra after ischemia
      by cortical devascularization.
AB  - The p75 neurotrophin receptor (p75(NTR)) is involved in neuronal functions
      ranging from induction of apoptosis and growth inhibition to the promotion of
      survival. p75(NTR) expression is induced in the central nervous system (CNS) by a
      range of pathological conditions, where it seems to have a role in neuronal death
      and axonal growth inhibition. The cellular mechanisms driving p75(NTR) expression
      in cell lines and primary neurons is Sp1 dependent (Ramos et al. [2007] J.
      Neurosci. 27:1498). In this study, we analyzed the spatiotemporal profile of
      p75(NTR) expression after an ischemic lesion induced by cortical
      devascularization (CD). Our results show that p75(NTR) expression occurs in
      isolated neurons of the ischemic lesion site. The p75(NTR+) neurons presented
      morphological alterations and active caspase-3 staining. Some p75(NTR+) neurons
      were also positive for sortilin. The peak of p75(NTR) expression was localized 3
      days postlesion (3DPL) in the penumbra. Sp1 transcription factor nuclear
      localization was observed in p75(NTR+) neurons. The overall level of Sp1
      expression was increased until 14DPL on the ipsilateral hemisphere. With primary
      cortical neurons, we demonstrated that p75(NTR) expression is induced by
      excitotoxic stress and correlated with increased Sp1 abundance. We conclude that
      p75(NTR) expression is localized in selected neurons of the ischemic lesion and
      that these neurons are probably condemned to apoptotic cell death. In primary
      neuronal culture, it is clear that excitotoxicity and Sp1 are involved in
      induction of p75(NTR) expression, although, in vivo, some additional mechanisms
      are likely to be involved in the control of p75(NTR) expression in specific
      neurons in vivo.

PMID- 19156870
TI  - Myelin-associated glycoprotein and its axonal receptors.
AB  - Myelin-associated glycoprotein (MAG) is expressed on the innermost myelin
      membrane wrap, directly apposed to the axon surface. Although it is not required
      for myelination, MAG enhances long-term axon-myelin stability, helps to structure
      nodes of Ranvier, and regulates the axon cytoskeleton. In addition to its role in
      axon-myelin stabilization, MAG inhibits axon regeneration after injury; MAG and a
      discrete set of other molecules on residual myelin membranes at injury sites
      actively signal axons to halt elongation. Both the stabilizing and the axon
      outgrowth inhibitory effects of MAG are mediated by complementary MAG receptors
      on the axon surface. Two MAG receptor families have been described, sialoglycans
      (specifically gangliosides GD1a and GT1b) and Nogo receptors (NgRs).
      Controversies remain about which receptor(s) mediates which of MAG's biological
      effects. Here we review the findings and challenges in associating MAG's
      biological effects with specific receptors.

PMID- 19156871
TI  - Distinct properties of murine alpha 5 gamma-aminobutyric acid type a receptors
      revealed by biochemical fractionation and mass spectroscopy.
AB  - Gamma-aminobutyric acid type A receptors (GABA(A)Rs) that contain the alpha 5
      subunit are expressed predominantly in the hippocampus, where they regulate
      learning and memory processes. Unlike conventional postsynaptic receptors,
      GABA(A)Rs containing the alpha 5 subunit (alpha 5 GABA(A)Rs) are localized
      primarily to extrasynaptic regions of neurons, where they generate a tonic
      inhibitory conductance. The unique characteristics of alpha 5 GABA(A)Rs have been
      examined with pharmacological, immunostaining, and electrophysiological
      techniques; however, little is known about their biochemical properties. The aim
      of this study was to modify existing purification and enrichment techniques to
      isolate alpha 5 GABA(A)Rs preferentially from the mouse hippocampus and to
      identify the alpha 5 subunit by using tandem mass spectroscopy (MS/MS). The
      results showed that the detergent solubility of the alpha 5 subunits was distinct
      from that of alpha1 and alpha2 subunits, and the relative distribution of the
      alpha 5 subunits in Triton X-100-soluble fractions was correlated with that of
      the extracellular protein radixin but not with that of the postsynaptic protein
      gephyrin. Mass spectrometry identified the alpha 5 subunit and showed that this
      subunit associates with multiple alpha, beta, and gamma subunits, but most
      frequently the beta 3 subunit. Thus, the alpha 5 subunits coassemble with similar
      subunits as their synaptic counterparts yet have a distinct detergent solubility
      profile. Mass spectroscopy now offers a method for detecting and characterizing
      factors that confer the unique detergent solubility and possibly cellular
      location of alpha 5 GABA(A)Rs in hippocampal neurons.

PMID- 19156872
TI  - CancerScope: patient assistance programs struggle during tough economic times -
      programs cannot serve all those who need help.

PMID- 19156873
TI  - Biochemical characterization of MLH3 missense mutations does not reveal an
      apparent role of MLH3 in Lynch syndrome.
AB  - So far 18 MLH3 germline mutations/variants have been identified in familial
      colorectal cancer cases. Sixteen of these variants are amino acid substitutions
      of which the pathogenic nature is still unclear. These substitutions are known as
      unclassified variants or UVs. To clarify a possible role for eight of these MLH3
      UVs identified in suspected Lynch syndrome patients, we performed several
      biochemical tests. We determined the protein expression and stability, protein
      localization and interaction of the mutant MLH3 proteins with wildtype MLH1. All
      eight MLH3 UVs gave protein expression levels comparable with wildtype MLH3.
      Furthermore, the UV-containing proteins, in contrast to previous studies, were
      all localized normally in the nucleus and they interacted normally with wildtype
      MLH1. Our different biochemical assays yielded no evidence that the eight MLH3
      UVs tested are the cause of hereditary colorectal cancer, including Lynch
      syndrome.

PMID- 19156874
TI  - Carotid artery stenosis: tailoring treatment according to risk profile.

PMID- 19156875
TI  - Endovascular carotid artery stenting and early coronary artery bypass grafting
      for asymptomatic carotid artery stenosis: long-term outcomes and neurologic
      events.
AB  - BACKGROUND: Optimal management of patients with asymptomatic critical carotid
      artery stenoses prior to coronary artery bypass grafting (CABG) has no clear
      consensus. Further, optimal timing for surgical coronary revascularization has
      not been defined after or with any carotid revascularization. METHODS: We
      reviewed the data from 2002 to 2007, of all patients in our institution who
      underwent carotid artery stenting (CAS) for critical carotid artery stenoses,
      prior to CABG. Twenty patients with critical carotid disease were referred for
      preoperative carotid intervention prior to CABG. Carotid duplex demonstrated
      evidence of critical stenoses in all patients. Patients were serially assessed by
      a stroke neurologist before and after the procedure (immediately, at 24 hr, at 48
      hr, immediately following CABG, and at 30 days). We evaluated initial procedural
      success as well as freedom from periprocedure stroke. RESULTS: Prior to
      undergoing CABG, 20 patients had stents placed in a single carotid artery for
      unilateral asymptomatic critical carotid artery stenoses. All the procedures,
      except one, were performed with distal embolic protection. Patients received
      aspirin and clopidogrel. There were no strokes or deaths up to a mean follow up
      of 486 days. The mean time from CAS to CABG performed in the same hospital
      admission was 6.4 days. Transfusion rates were not excessive despite dual
      antiplatelet therapy. CONCLUSION: In a real-world setting, endovascular
      extracranial CAS for asymptomatic carotid artery stenosis by experienced
      operators, prior to CABG was safe and permitted early coronary revascularization
      without increased risk of strokes or death in this high-risk cardiovascular
      patient population.

PMID- 19156876
TI  - Optimizing outcomes for patients with severe carotid and coronary disease.

PMID- 19156877
TI  - Percutaneous endovascular treatment for isolated spontaneous superior mesenteric
      artery dissection: report of two cases and literature review.
AB  - Isolated spontaneous superior mesenteric artery (SMA) dissection is a rare and
      sporadically reported condition. Therapeutic options include medical treatment,
      surgery, and endovascular treatment. However, the optimal treatment strategy has
      still not been established. We herein present two patients with acute abdomen due
      to isolated spontaneous SMA dissection, in whom symptoms remained despite initial
      anticoagulation therapy. Percutaneous endovascular treatment with stenting of the
      dissected main trunk to achieve complete coverage of the entry site and balloon
      angioplasty for the distally involved side branches were performed successfully
      and resulted in complete resolution of the symptoms. According to our experience
      and previous case reports, early (within 1 week) elective percutaneous
      endovascular intervention with background anticoagulation therapy is a feasible
      and effective treatment strategy for symptomatic patients with isolated SMA
      dissection.

PMID- 19156878
TI  - A novel approach for percutaneous treatment of massive nonocclusive mesenteric
      ischemia: tolazoline and glycerol trinitrate as effective local vasodilators.
AB  - Nonocclusive mesenteric ischemia (NOMI) generally affects patients with low
      cardiac output, resulting in splanchnic hypoperfusion. It includes all forms of
      mesenteric ischemia without vessel occlusion and makes up between 20 and 30% of
      all cases of acute mesenteric ischemia. We present the case of a 84-year-old man
      with a history of total atrioventricular block developing NOMI. This was
      diagnosed by percutaneous selective catheter arteriography (PSCA), which
      demonstrated remarkable abrupt termination of the jejunal vasculature and
      multiple severe spasms of the colonic arteries. Control PSCA after local
      intraarterial vasodilator therapy (LIVT) with tolazoline and glycerol trinitrate
      documented an excellent therapeutic result with a completely unremarkable
      vasculature. Although LIVT was complicated by severe cardiovascular complications
      inclusive of cardiac arrest with the need of cardiopulmonary resuscitation, the
      patient fully recovered and was discharged after implantation of a cardiac
      pacemaker in good clinical condition 7 days later.

PMID- 19156879
TI  - External-to-internal iliac artery endografting for the exclusion of iliac artery
      aneurysms: an alternative technique for preservation of pelvic flow?
AB  - PURPOSE: The purpose of this study was to describe an alternative endovascular
      procedure to exclude iliac artery aneurysms, preserving perfusion to the internal
      iliac artery. CASES: Two patients, considered unfit for open repair, underwent
      endovascular repair of iliac artery aneurysms. One of these occurred after
      previous placement of a bifurcated prosthesis. In both cases the aneurysms were
      excluded using a nitinol stent covered with expanded polytetrafluoroethylene from
      the external to the internal iliac artery. Using this technique, the internal
      iliac arteries were perfused in a retrograde manner. Both interventions were
      technically successful. The external-to-internal endograft remained patent after
      6 and 16 months, respectively. CONCLUSION: Endovascular placement of a stent
      graft from the external iliac artery into the internal iliac artery may offer an
      alternative and minimal invasive alternative for the management of common and
      internal iliac artery aneurysms. With the use of this technique, pelvic perfusion
      is preserved. Further studies are warranted to appraise the advantages and risk
      of this approach for iliac artery aneurysms.

PMID- 19156880
TI  - Compression of the left main coronary from right pulmonary artery stent:
      precaution in pediatrics, possibility in adults?

PMID- 19156881
TI  - Inflation time and drug-eluting stent: the longer, the better...

PMID- 19156882
TI  - Long-term mortality after bolus-only administration of abciximab, eptifibatide,
      or tirofiban during percutaneous coronary intervention.
AB  - OBJECTIVE: To evaluate the long-term mortality after bolus-only administration of
      abciximab, eptifibatide, and tirofiban during percutaneous coronary intervention
      (PCI). BACKGROUND: Studies on platelet glycoprotein IIb/IIIa receptor inhibitors
      (GPI) administered as bolus-only during PCI suggest that this strategy may be
      similar in efficacy, safer, and more cost-effective compared to a bolus plus
      infusion of GPI. METHODS: We evaluated 864 patients (abciximab = 274,
      eptifibatide = 361, and tirofiban = 229) who underwent PCI with a bolus-only
      regimen during January 2003 to August 2005. RESULTS: After a median follow up of
      four (interquartile range, 3-4.5) years, there were a total of 95 (11%) deaths.
      The survival rate was 83% in the abciximab group, 91% in the eptifibatide group,
      and 93% in the tirofiban group (P = 0.003 by log-rank test). After adjustment for
      baseline clinical and procedural characteristics using a Cox proportional hazards
      model, the abciximab group had a significantly higher mortality compared to the
      eptifibatide group (P = 0.003; Hazard ratio (HR) for eptifibatide compared to
      abciximab was 0.49 (95% confidence intervals [CI]: 0.30-0.78). The long-term
      mortality was not significantly different in the tirofiban group compared to the
      abciximab group (P = 0.33) or the eptifibatide group (P = 0.20), perhaps because
      of shorter follow-up period and fewer patients in the tirofiban group.
      CONCLUSION: When given as bolus-only during PCI, eptifibatide may improve long
      term survival compared to abciximab.

PMID- 19156883
TI  - The benefits and risks of abciximab, eptifibatide, or tirofiban during PCI: class
      effects or do they differ?

PMID- 19156884
TI  - Stump(er)ed for a solution. Earlier may be better?

PMID- 19156885
TI  - Stenting of stenotic or occluded iliofemoral veins, superior and inferior vena
      cavae in children with congenital heart disease: acute results and intermediate
      follow up.
AB  - OBJECTIVES: To determine the short and intermediate term outcome following
      systemic venous stent placement in children with congenital heart disease.
      BACKGROUND: Patients with congenital heart disease are at risk of stenosis or
      occlusion of systemic veins following indwelling lines or catheterizations. Stent
      dilation may ameliorate symptoms and open the vessel for use during future
      procedures. We report our acute and intermediate results. METHODS: All patients
      with systemic venous stent placement in the iliofemoral veins, inferior or
      superior vena cava at our institution between 1998 and 2006 were included.
      Initial and the follow-up catheterization data were reviewed retrospectively.
      RESULTS: 70 stents were placed in 33 patients (36 vessels). Median age was 2.6
      years (0.2-14.2) and weight 11.5 kg (3.8-78.7). 17/36 vessels (47%) were occluded
      requiring recanalization. Following stent delivery, the mean minimum vessel
      diameter increased from 3.1 +/- 3.2 to 7.2 +/- 3.0 mm (P < 0.001). There were no
      major complications. Seventeen patients and vessels had a total of 62 follow-up
      catheterizations, with median length of follow-up 4.1 years (0.7-9.3). During
      intermediate follow up, 7/17 vessels (41%) required additional intervention. Six
      patients had additional balloon dilation of existing stents, and one additional
      stent was placed. Vessels were further dilated to 8.4 +/- 3.5 mm at the last
      catheterization. CONCLUSION: Systemic venous stents are safe and effective in
      recanalizing stenosed or occluded vessels. At follow-up, reocclusion can occur,
      however, previously placed stents can be safely recanalized if necessary. Future
      studies will determine if stenting is indicated in a broader population.

PMID- 19156886
TI  - Systemic vein stents--a solution to a growing challenge.

PMID- 19156887
TI  - Long-term follow-up of the STARFlex device for closure of secundum atrial septal
      defect.
AB  - BACKGROUND: There is limited published outcome data on the STARFlex device for
      transcatheter closure of atrial septal defects (ASD). AIM: To contribute to the
      long term outcomes of ASD device closure with the STARFlex device. METHODS:
      Results of a prospective FDA approved clinical trial (1999-2001) from a single
      institution of the STARFlex device for simple ASD was reviewed. The inclusion
      criteria included age >or=2 years, isolated secundum ASD, evidence of right
      ventricular volume overload, and maximum stretched diameter <22 mm. A
      retrospective review of the original study data with most recent follow-up was
      performed. Clinical success in the trial was defined as complete closure or
      residual leak <or=2 mm, absence of a severe complication and no need for an
      additional device or surgery to treat the ASD. RESULTS: Twenty seven (27)
      patients were prospectively enrolled in the study period with a procedural
      success in 23 (85%). There were two severe complications, both 40 mm device
      embolizations that underwent semiurgent surgical intervention for device removal
      and ASD closure (40 mm device subsequently withdrawn from trial). Device
      placement was unsuccessful in two patients due to malposition related to an
      insufficient retro-aortic rim, with elective surgical closure. Unsuccessful
      procedural outcomes were statistically associated with deficient rims (P < 0.01).
      Of the 23 long term follow-up device patients, 23 (100%) achieved clinical
      success: 22 (96%) had complete closure at 1 year and latest echocardiographic
      follow-up and one case had a small <2 mm residual defect that has persisted.
      There have been no late complications with normalization of RV volumes in 92% and
      no deleterious ECG changes. Device fractures occurred in 8/23 (35%) devices and
      were more common in the larger devices (P < 0.05) but had no sequelae. None
      required any further intervention to treat the ASD and there were no infectious
      or thrombotic issues. CONCLUSIONS: In this cohort the STARFlex device for
      secundum ASD closure provided procedural success in 85% with failures due to
      surgical referral. All 23 patients with a STARFlex device with available long
      term follow-up had clinical success. Further long term data is required.

PMID- 19156888
TI  - It takes two to flirt with a dimeric RNase.
AB  - In my long RNase-life-time I have had the fortune to entertain with Lelio
      Mazzarella what I have called special interactions, which not only advanced my
      knowledge of proteins but also gave pleasure, as one obtains by reading a
      beautiful book, an inspiring poem, or watching a very good movie. In this
      article, I recall the more than 30-year long story of these interactions in which
      "it took two," a structural biologist with his coworkers and a biochemist with
      his coworkers, to flirt with an unusual, dimeric RNase.

PMID- 19156889
TI  - Long-term follow-up of the Starflex device for closure of secundum atrial septal
      defect.

PMID- 19156890
TI  - Left main coronary artery compression from right pulmonary artery stenting.
AB  - Complications related to pulmonary artery stenting include stent migration,
      jailing of vessels, vessel rupture, and compression of surrounding structures.
      Compression of the left main coronary artery (LMCA) as a result of stent
      placement in the right pulmonary artery (RPA) is extremely rare. We present two
      patients post repair of congenital heart disease who suffered LMCA compression
      following RPA stenting. The first patient experienced acute coronary
      insufficiency in the cardiac catheterization laboratory, whereas the second
      patient had a more chronic course. We also present a third patient who had a CT
      angiogram that demonstrated a close spatial relationship between the RPA and the
      LMCA. Based on our previous experiences, we felt that this patient was at
      significant risk for LMCA compression if the RPA were stented. Coronary
      compression is rare complication of pulmonary artery stenting but should be
      considered in cases with history of repaired congenital heart disease.

PMID- 19156891
TI  - In vitro and in vivo studies on thermistor-based intracoronary temperature
      measurements: effect of pressure and flow.
AB  - BACKGROUND: Intracoronary thermography has been proposed to detect vulnerable
      plaques. We hypothesized that changes in coronary pressure and flow in the
      coronary tree may interfere with the temperature measurements obtained with
      thermistors. METHODS AND RESULTS: First, a very close correlation was found in
      vitro between the temperature measured by a thermocouple and by a thermistor
      based temperature measuring guide wire (PressureWire, PW) over a large
      temperature range. Second, the PW was tested in a vitro low pressure model of
      "hot plaque". The sensor of the PW could detect changes in temperature of the
      wall of 0.5 degrees C as long as the distance from the wall was less than 0.5 mm
      and the flow less than 60 mL/min. Third, in 18 patients with an acute myocardial
      infarction, intracoronary pressure and temperature variations were assessed.
      Although crossing the occlusion, the temperature rose by 0.059 +/- 0.02 degrees C
      and this increase was correlated with the distal coronary pressure (r = 0.72, P <
      0.001). Fourth, a balloon coronary occlusion (BCO) with the sensor distally in
      the distal part of the vessel (low flow/low pressure conditions) systematically
      induced an increase in temperature (0.14 +/- 0.07 degrees C) while with the
      sensor proximally to the balloon occlusion (low flow/normal pressure conditions),
      no change occurred. CONCLUSION: Taken together these observations suggest that
      thermistor-based sensors are not suited for assessing thermal heterogeneity in
      the vascular wall and that the data obtained so far in patients with acute
      coronary syndromes might have been flawed by pressure (and flow) artifacts.

PMID- 19156892
TI  - Automated left ventricular delineation in X-ray angiograms: a validation study.
AB  - OBJECTIVES: Recently an automated analysis approach for left ventricular (LV) X
      ray angiographic studies was proposed. This particular study aims to assess the
      clinical potential of this approach. BACKGROUND: Over the past 30 years much
      research has been carried out to develop a technique with automated contour
      detection of the LV outline in the end-diastolic (ED) and end-systolic (ES)
      phases. Very few have made it into clinical practice. Our latest approach is
      based on innovative model-based image processing techniques. METHODS: Two expert
      cardiologists analyzed 30 patient studies both by contouring the LV manually and
      by using the proposed automated methodology. In the latter procedure the experts
      were allowed to edit the automatically generated contours manually. The manual,
      automatic, and edited automatic contours were compared, focusing on accuracy,
      workflow efficiency, and inter- and intra-observer variabilities. RESULTS: No
      significant differences between the automatically derived and manual LV volumes
      were observed. The average patient study analysis time was reduced by 26%, from
      4.2 to 3.1 min. When editing was required, 19% of the ED and 25% of the ES
      contour length needed manual correction. Furthermore, a reduction in inter
      observer variability of 12.4% was observed. CONCLUSIONS: Using the proposed
      automated methodology for X-ray LV angiographic study analysis, a considerable
      reduction in required analysis time and manual effort is achieved. Because the
      acquired results are of clinically acceptable quality and the inter- and intra
      observer variabilities are reduced, this automated approach has the potential to
      optimize the analysis workflow for LV X-ray angiography in clinical practice.

PMID- 19156893
TI  - The death or the rebirth of the left ventriculogram?

PMID- 19156894
TI  - Infections and association with different intensity of chemotherapy in children
      with acute myeloid leukemia.
AB  - BACKGROUND: The objectives were to compare infections during different
      intensities of therapy in children with acute myeloid leukemia (AML). METHODS:
      Subjects were children enrolled in Children's Cancer Group 2891 with AML. In
      phase 1 (induction), patients were randomized to intensive or standard timing. In
      phase 2 (consolidation), those with a family donor were allocated allogeneic stem
      cell transplantation (SCT); the remainder were randomized to autologous SCT or
      chemotherapy. This report compares infections between different treatments on an
      intent-to-treat basis. RESULTS: During phase 1, intensive timing was associated
      with more bacterial (57.7% vs 39.4%; P < .001), fungal (27.4% vs 9.9%; P < .001),
      and viral (14.0% vs 3.9%; P < .001) infections compared with standard timing.
      During phase 2, chemotherapy was associated with more bacterial (56.5% vs 40.1%;
      P = .005), but similar fungal (9.5% vs 6.1%; P = 1.000) and viral (4.2% vs 12.9%;
      P = .728) infections compared with allogeneic SCT. No differences between
      chemotherapy and autologous SCT infections were seen. Fatal infections were more
      common during intensive compared with standard timing induction (5.5% vs 0.9%; P
      = .004). Infectious deaths were similar between chemotherapy, autologous SCT, and
      allogeneic SCT. CONCLUSIONS: Prevalence of infection varies depending on the
      intensity and type of treatment. This information sheds insight into the
      mechanisms behind susceptibility and outcome of infections in pediatric AML.

PMID- 19156895
TI  - Postmenopausal hormone use and breast cancer associations differ by hormone
      regimen and histologic subtype.
AB  - BACKGROUND: Data from large prospective studies are needed to fully characterize
      the impact of exogenous hormones on breast cancer incidence by type of hormone
      preparation and histology of the cancer. METHODS: In a prospective cohort of
      67,754 postmenopausal women in the US, 1821 cases of invasive ductal cancer and
      471 cases of invasive lobular or mixed lobular cancer occurred during 13 years of
      follow-up. The authors computed age-adjusted rates, as well as age-adjusted and
      multivariate-adjusted rate ratios (RR) for ductal and lobular breast cancer and
      for the use of estrogen only (E-only) and estrogen and progesterone (E + P) for
      current and former hormone users by duration of use and years since last use.
      RESULTS: Current use of E + P was associated with an increased risk of both
      ductal (RR of 1.75; 95% confidence interval [95% CI], 1.53-2.01) and lobular (RR
      of 2.12; 95% CI, 1.62-2.77) breast cancer. Risk increased within the first 2 to 3
      years of use and attenuated 2 years after cessation. In contrast, current use of
      E-only was not associated with an overall increased risk of invasive ductal
      cancer. The only exceptions to this finding were in lean (body mass index <25)
      women and for ductal cancers diagnosed at the regional/distant stage, where in
      both cases the use of E-only was associated with an increased risk. E-only use
      was associated with a 50% increased risk of invasive lobular cancer after >or=10
      years of use. CONCLUSIONS: Use of E + P is more detrimental to the breast than E
      only use, in terms of both ductal and lobular cancer. The findings from the
      current study suggest a window of 2 to 3 years for the risks of E + P both to
      become apparent after initial use and to attenuate after cessation.

PMID- 19156896
TI  - Real world safety and efficacy of the Janus Tacrolimus-Eluting stent: long-term
      clinical outcome and angiographic findings from the Tacrolimus-Eluting STent
      (TEST) registry.
AB  - OBJECTIVES: We sought to evaluate the safety and performance of the Janus
      Tacrolimus-Eluting stent (TES) in an unselected population of patients, without
      application of restrictive clinical or angiographic criteria. BACKGROUND:
      Continued attention to the safety, efficacy, and deliverability of first
      generation drug eluting stents has led to the development of new
      antiproliferative agents with alternative stent platforms and different drug
      carrier vehicles. METHODS: The TEST (Tacrolimus Eluting STent) registry is a
      prospective, nonrandomized single-center registry in which 140 consecutive
      patients who underwent single- or multi-vessel percutaneous coronary intervention
      between February 2005 and August 2005 were enrolled. RESULTS: The composite rate
      of major adverse cardiac events (MACE) at 22 months clinical follow-up was 40.9%.
      The rate of mortality, myocardial infarction, and target lesion revascularization
      (TLR) were 5.5%, 11%, and 31.5%, respectively. Angiographic follow-up at 8 months
      was achieved in 74% of patients; binary restenosis occurred in 39.4% of lesions.
      Most restenosis lesions (94.6%) had a diffuse pattern, while focal restenosis was
      observed in 5.4% of cases. Definite or probable stent thrombosis was observed in
      2.4% of patients. CONCLUSIONS: The present prospective, nonrandomized, TEST
      registry indicated high MACE and restenosis rates, and thereby rather
      discouraging long-term outcomes with use of the Janus TES in an unselected "real
      world" population of patients who underwent single- or multi-vessel percutaneous
      coronary intervention.

PMID- 19156897
TI  - A critical appraisal of the Janus carbostent.

PMID- 19156898
TI  - Percutaneous closure of an iatrogenic atrial septal defect.
AB  - The use of the Tandem Heart percutaneous ventricular assist device (Tandem Heart
      pVAD, Cardiac Assist technologies, Pittsburgh, PA) as a bridge to recovery or to
      other cardiopulmonary support systems has been rising. One requirement for
      placement of this device is an intraatrial septostomy which is usually closed
      during the surgical insertion of more permanent ventricular assist devices. We
      present a case of a 62-year-old man with a residual acquired atrial septal defect
      (ASD) from Tandem Heart placement, which could not be closed surgically during
      insertion of left and right ventricular assist devices. The patient remained
      intubated and hypoxemic after removal of his right ventricular assist device due
      to the presence of persistent right to left shunting. With closure of the ASD
      using an 8-mm Amplatzer septal occluder (ASO; AGA Medical Corp., Golden Valley,
      MN) the patient stabilized and was successfully extubated.

PMID- 19156899
TI  - Microtubule-damaging agents enhance RASSF1A-induced cell death in lung cancer
      cell lines.
AB  - BACKGROUND: Tumor suppressor gene product RASSF1A has been reported to induce
      mitotic arrest and apoptosis through its interaction with microtubule and binding
      to the Ras effector NORE1. Despite this promising antitumor action of microtubule
      targeted drugs, clinical studies demonstrated that paclitaxel (TXL) and
      vincristine (VCS) have differential antitumor effects, depending on the status of
      microtubule-related genes in lung cancer patients. In this study, to provide
      effective chemotherapeutic treatment for lung cancer patients with the
      microtubule-targeted drugs, the authors investigated whether RASSF1A could
      enhance sensitivity to TXL and VCS, as an intrinsic microtubule modulator, in
      nonsmall cell lung cancer (NSCLC) cells. METHODS: The growth inhibitory effects
      of TXL and VCS on RASSF1A-transfected cells were assessed using clonogenic and
      flow cytometry-based propidium iodide-labeled assay. The levels of mitosis
      related proteins in RASSF1A-transfected cells after treatment with TXL or VCS
      were examined by Western blot analysis and in vitro kinase assay. RESULTS:
      RASSF1A enhanced the growth inhibitory effect of TXL and VCS on NSCLC cells and
      bronchial epithelial transformed cells (BEAS-2B) by inducing cell cycle arrest at
      the G2/M-phase. Accumulation of cyclin B1, G2/M-phase-related protein, was
      observed when RASSF1A-transfected H1299 cells were treated with TXL or VCS,
      accompanied with an increase of cyclin A. Inhibition of the activity of cyclin
      B1/Cdc2 complex by RASSF1A and TXL or VCS was confirmed by kinase assay and
      knockdown of RASSF1A expression by using small interfering RNA. CONCLUSIONS:
      RSAAF1A protein has a cooperative growth inhibitory effect with microtubule
      targeted drugs through cyclin B1 accumulation on NSCLC cells, suggesting novel
      insights for the selection of chemotherapeutic agents.

PMID- 19156900
TI  - Successful recanalization of a chronic occluded left anterior descending coronary
      artery with a modification of the retrograde proximal true lumen puncture
      technique: the antegrade microcatheter probing technique.
AB  - Chronic total occlusions (CTO) still remain one of the most technically
      challenging fields in interventional cardiology. Here we report a case of
      successful retrograde recanalization of an occluded proximal left anterior
      descending coronary artery with a modification of the "retrograde proximal true
      lumen puncture" technique. By combining this strategy with a novel antegrade
      guide wire access through a microcatheter which was placed into the antegrade
      guiding catheter with the "reverse anchoring balloon" technique (the "antegrade
      microcatheter probing" technique), the need for retrograde CTO lesion dilatations
      has been eliminated, making the procedure easier and faster. This modified
      retrograde approach might provide a feasible and safe technique for antegrade
      guide wire access during retrograde CTO recanalization.

PMID- 19156901
TI  - Revascularization of the impenetrable CTO--in support of enhanced antegrade
      approach.

PMID- 19156902
TI  - Genetic polymorphisms of CYP2D6 10 and CYP2C19 2, 3 are not associated with
      prognosis, endometrial thickness, or bone mineral density in Japanese breast
      cancer patients treated with adjuvant tamoxifen.
AB  - BACKGROUND: The authors investigated the impact of the genetic polymorphisms
      cytochrome P450 (CYP) family 2, subfamily D, polypeptide 6, allele 10 (CYP2D6 10)
      and CYP family 2, subfamily C, polypeptide 19, allele 2, 3 (CYP2C19 2, 3) on
      disease recurrence in patients with breast cancer who received adjuvant tamoxifen
      and evaluated the impact of those polymorphisms on endometrial thickness, bone
      mineral density (BMD), and serum total cholesterol levels. METHODS: Patients with
      primary breast cancer (n=173) who had hormone receptor-positive tumors and who
      also received adjuvant tamoxifen were included in the current study. Genetic
      polymorphisms of CYP2D6 10 and CYP2C19 2, 3 were analyzed. RESULTS: Recurrence
      free survival (RFS) rates did not differ significantly between patients with the
      CYP2D6 10/10 genotype (n=40) and patients with the CYP2D6 wild-type (wt)/wt or
      wt/10 genotype (n=133) or between patients with the CYP2C19 2/2, 2/3, or 3/3
      genotypes (n=41) and patients with the CYP2C19 wt/wt, wt/2, or wt/3 genotype
      (n=132). Multivariate analysis indicated that, even after adjustment for well
      established prognostic factors, these CYP2D6 or CYP2C19 genotypes were not
      associated significantly with the RFS rate. Moreover, these genotypes did not
      affect endometrial thickness, BMD, or total cholesterol levels 1 year after the
      start of tamoxifen treatment. CONCLUSIONS: Neither the CYP2D6 10/10 genotype nor
      the CYP2C19 genotype is likely to have a clinically significant impact on
      prognosis, endometrial thickness, BMD, or total cholesterol levels in Japanese
      patients with breast cancer who are treated with adjuvant tamoxifen.

PMID- 19156903
TI  - Long-term outcome for men with teratoma found at postchemotherapy retroperitoneal
      lymph node dissection.
AB  - BACKGROUND: Patients with pure teratoma within the postchemotherapy
      retroperitoneal lymph node dissection (PC-RPLND) specimen traditionally have been
      considered at low risk for disease progression. The objectives of this study were
      to determine the disease-related outcomes of patients who had pure teratoma
      identified at the time of PC-RPLND and to examine the prognostic value of
      clinical variables that were identified previously as important predictors of
      disease recurrence in these patients. METHODS: Between 1980 and 2003, 97 patients
      with metastatic nonseminomatous germ cell tumor and pure teratoma histology at
      the time of PC-RPLND were identified. The medical records of these patients were
      reviewed retrospectively for pertinent clinical and treatment-related outcomes.
      RESULTS: At a median follow-up of 7.4 years, 21 patients (22%) developed
      recurrent disease after PC-RPLND. The 5-year and 10-year probabilities (+/
      standard error) of freedom from disease recurrence were 81%+/-4% and 76%+/-5%,
      respectively. The postchemotherapy alpha-fetoprotein (AFP) level and mediastinal
      involvement at presentation were statistically significant predictors of disease
      recurrence on multivariate analysis. Nine of 97 patients (9.3%) died from testis
      cancer, and 4 patients died from other causes. CONCLUSIONS: In patients with pure
      teratoma histology at PC-RPLND, mediastinal involvement at presentation and the
      presence of an elevated AFP level before PC-RPLND predicted an unfavorable
      outcome. The absence of mediastinal involvement and normal AFP level, however,
      did not confirm freedom from disease recurrence. Patients who had teratoma at the
      time of PC-RPLND remained at considerable risk for disease progression because of
      the unpredictable nature of teratoma and the presence of unrecognized, active
      germ cell disease outside the retroperitoneum.

PMID- 19156905
TI  - Carbon ion radiotherapy for pediatric patients and young adults treated for
      tumors of the skull base.
AB  - BACKGROUND: The current study was conducted to evaluate the outcome of carbon ion
      radiotherapy (RT) in children and young adults with skull base chordomas and
      chondrosarcomas. METHODS: Between 1997 and 2007, 394 patients were treated with
      carbon ion RT at Gesellschaft fur Schwerionenforschung in Darmstadt, Germany. Of
      these patients, 17 patients were aged<or=21 years. Seventeen of these young
      patients were treated for chordoma or low-grade chondrosarcoma of the skull base
      and were analyzed in this study. Irradiation was performed after primary
      diagnosis in 14 patients (82%) and for recurrent tumors in 3 patients (18%). The
      authors applied a median total dose of 60 gray equivalents (Gy E) (range, 60-66.6
      Gy E) in a fractionation of 7x3 Gy E per week of carbon ion RT using the raster
      scan technique. All patients were observed prospectively on a regular basis after
      carbon ion RT. RESULTS: The median follow-up time was 49 months. Treatment was
      well tolerated without severe side effects and could be completed on an
      outpatient basis in all patients without interruptions. One patient with chordoma
      developed tumor progression at 60 months after carbon ion RT. All other patients
      demonstrated no signs of tumor progression during follow-up. CONCLUSIONS: Despite
      its promising outcome in children and young adults with chordomas and
      chondrosarcomas, further evaluation in a larger patient collective is required.
      Randomized studies comparing the outcome after carbon ion RT with proton RT are
      especially needed to evaluate the role of particle beams in the treatment of
      skull base tumors in children and young adults.

PMID- 19156909
TI  - Characterization and potential function of a novel pre-implantation embryo
      specific RING finger protein: TRIML1.
AB  - Members of the super-class of zinc finger proteins are key regulators in early
      embryogenesis. Utilizing in silico mining of EST Databases for pre-implantation
      Embryo-Specific Zinc Finger Protein Genes, we characterized a novel zygotic mouse
      gene-tripartite motif family-like 1 (TRIML1), which expresses in embryo before
      implantation. Knocking down of TRIML1 resulted in the fewer cell number of
      blastocysts and failture to give rise to neonates after embryo transfer. The
      binding partner of TRIML1, Ubiquitin-specific protease 5 (USP5), was identified
      by yeast two-hybrid screening assay. The interaction was confirmed by GST pull
      down and coimmunoprecipitation analysis. The role of TRIML1 in ubiquitin pathway
      during the development stage of mouse blastocyst was further discussed.

PMID- 19156910
TI  - Epidemiological association between C-reactive protein and prostate-specific
      antigen.

PMID- 19156911
TI  - Targeted therapies in squamous cell carcinoma of the head and neck.
AB  - Head and neck cancer is a challenging disease that is expected to account for
      greater than 500,000 new cases worldwide in 2008. Toxicity has impeded advances
      in chemotherapy and radiation for head and neck cancer, and the prognosis for
      patients with recurrent and/or metastatic disease remains poor. Over the past
      decade, clinical research in head and neck cancer has focused on improving the
      efficacy of current multimodal approaches by targeting cellular pathways
      associated with carcinogenesis. Blocking the epidermal growth factor receptor
      (EGFR) and the vascular endothelial growth factor receptor (VEGFR) have emerged
      as primary strategies that account for the success of current targeted therapies
      in cancer. Recent studies with cetuximab, a monoclonal antibody inhibitor of the
      EGFR, have demonstrated survival benefits across the range of treatment settings
      in advanced head and neck cancer, and it is the only targeted therapy approved
      for use in this malignancy. In this review, the authors present the current
      development status of targeted therapies, focusing on those that have potential
      to impact the management of head and neck cancer in the near-term future. Trials
      are ongoing in all stages of disease and with a variety of modalities and agents,
      and those trials should provide critical insight into the best way to use these
      agents to improve patient outcomes.

PMID- 19156912
TI  - Delivery of nerve growth factor to brain via intranasal administration and
      enhancement of brain uptake.
AB  - The main objective of the study was to investigate the efficacy of chitosan to
      facilitate brain bioavailability of intranasally administered nerve growth factor
      (NGF). In vitro permeability studies and electrical resistance studies were
      carried out across the bovine olfactory epithelium using Franz diffusion cells.
      The bioavailability of intranasally administered NGF in rat hippocampus was
      determined by carrying out brain microdialysis in Sprague-Dawley rats. The in
      vitro permeation flux across the olfactory epithelium of NGF solution without
      chitosan (control) was found to be 0.37 +/- 0.06 ng/cm(2)/h. In presence of
      increasing concentration of chitosan (0.1%, 0.25%, and 0.5%, w/v) the permeation
      flux of NGF was found to be 2.01 +/- 0.12, 3.88 +/- 0.19, and 4.12 +/- 0.21
      ng/cm(2)/h respectively. Trans-olfactory epithelial electrical resistance
      decreased approximately 34.50 +/- 4.06% in presence of 0.25% (w/v) chitosan. The
      C(max) in rats administered with 0.25% (w/v) chitosan and NGF was 1008.62 +/-
      130.02 pg/mL, which was significantly higher than that for rats administered with
      NGF only 97.38 +/- 10.66 pg/mL. There was approximately 14-fold increase in the
      bioavailability of intranasally administered NGF with chitosan than without
      chitosan. Chitosan can enhance the brain bioavailability of intranasally
      administered NGF.

PMID- 19156913
TI  - Incidence of bisphosphonate-associated osteonecrosis of the jaws in breast cancer
      patients.
AB  - BACKGROUND: Bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) is a
      relatively new disease. The aim of this study was to evaluate the prevalence of
      BP-ONJ in breast cancer patients with osseous metastasis and bisphosphonate
      therapy. METHODS: A retrospective study was conducted in a EUSOMA accredited
      breast unit in Germany. All patients treated from January of 2000 to March of
      2006 with metastatic breast cancer and bisphosphonate therapy were reviewed. All
      patients were contacted, and missing data were completed through structured
      interviews with their dentists and physicians (n = 75). Primary outcome was the
      development of BP-ONJ and the detection of possible additional trigger factors
      for the development of BP-ONJ. RESULTS: A total of 117 patients with breast
      cancer fulfilled the inclusion criteria, and data for 75 still living patients
      were included. Of these 75, 4 patients developed a BP-ONJ, resulting in a
      prevalence of 5.3%: 3 patients received zoledronate only; 1 patient had first
      pamidronate followed by zoledronate and ibandronate. A tooth extraction could be
      identified as an additional trigger factor for 2 patients. CONCLUSIONS: With a
      prevalence of 5.3%, BP-ONJ in breast cancer patients has become a relevant
      disease that should be discussed with patients for whom bisphosphonates have been
      recommended. Appropriate dental care before bisphosphonate therapy commences has
      been advised to reduce the occurrence of BP-ONJ.

PMID- 19156914
TI  - Development and evaluation of perfluorocarbon nanobubbles for apomorphine
      delivery.
AB  - Apomorphine is a dopamine receptor agonist for treating Parkinson's disease.
      However, its clinical application is limited by its instability and the need for
      frequent injections. The aim of the present work was to develop acoustically
      active perfluorocarbon nanobubbles (PNs) for encapsulation of both apomorphine
      HCl and base forms to circumvent these delivery problems. The PNs were prepared
      using coconut oil and perfluoropentane as the inner phase, which was emulsified
      by phospholipids and cholesterol. The morphology, size, zeta potential, and drug
      release of the PNs were characterized. The particle size ranged from 150 to 380
      nm, with differences in the oil or perfluorocarbon ratio in the formulations.
      Atomic force microscopy confirmed oval- or raisin-shaped particles and a narrow
      size distribution of these systems (polydispersity index = 0.25-0.28). The
      stability experimental results indicated that PNs could protect apomorphine from
      degradation. Evaporation of the PNs at 37 degrees C was also limited. Apomorphine
      HCl and base in PNs showed retarded and sustained release profiles. Ultrasound
      imaging confirmed the echogenic activity of PNs developed in this study. The
      apomorphine HCl release by insonation at 1 MHz showed enhancements of two- to
      fourfold compared to the non-ultrasound group, illustrating a possible drug
      targeting effect. On the contrary, apomorphine base showed a decreased release
      profile with ultrasound application. Apomorphine-loaded PNs showed promising
      stability and safety. They were successful in sustaining apomorphine delivery.

PMID- 19156915
TI  - Frequent loss of heterozygosity of chromosome 1q in esophageal adenocarcinoma:
      loss of chromosome 1q21.3 is associated with shorter overall survival.
AB  - BACKGROUND: Previous microarray expression profiling studies have shown that
      genes located on chromosome region 1q21-23 were down-regulated in the progression
      of Barrett esophagus to esophageal adenocarcinoma and that, among patients with
      the latter condition, these genes were differentially expressed between
      responders and nonresponders of preoperative chemoradiation therapy. It was
      unclear whether this difference was due to loss of heterozygosity (LOH) or to
      other genetic alterations at this locus. METHODS: The status of chromosome 1q LOH
      was retrospectively evaluated in formalin-fixed, paraffin-embedded pretreatment
      biopsy specimens from 33 patients with locally advanced esophageal adenocarcinoma
      who were treated with preoperative neoadjuvant therapy, and the findings were
      correlated with clinicopathologic features and overall survival duration. LOH was
      determined by polymerase chain reaction analysis of 7 dinucleotide microsatellite
      markers that spanned chromosomal region 1q21-23. RESULTS: Allelic loss of
      chromosome 1q with any marker was found in 66% of tumors; 58% of tumors
      demonstrated loss of chromosome 1q21, and 45% of tumors demonstrated loss of
      chromosome 1q23. Patients with loss of chromosome 1q21.3 had shorter overall
      survival duration than patients without loss of chromosome 1q21.3 (P = .02). The
      difference in survival with loss of the chromosome 1q21.3 region was also found
      to be significant in a subset of patients with incomplete pathologic response to
      preoperative therapy (P = .024). CONCLUSIONS: Loss of chromosome 1q was a
      frequent finding in esophageal adenocarcinoma cases, and loss of the 1q21.3
      region was associated with shorter overall survival duration.

PMID- 19156916
TI  - Glucose as a prognostic factor in ovarian carcinoma.
AB  - BACKGROUND: Research suggests that glucose levels in cancer patients may be an
      important prognostic indicator. In ovarian tumors, increased expression of
      glucose transporter 1 (GLUT1), a transmembrane protein responsible for glucose
      uptake, is related to shorter survival time in ovarian cancer patients. This
      study tested the hypothesis that higher presurgical glucose levels predict
      shorter disease-specific survival time and time to recurrence in ovarian cancer
      patients. METHODS: Nonfasting plasma glucose levels were determined for 74
      patients with ovarian cancer at the time of their presurgical consultation and
      for 125 ovarian cancer patients in an independent validation set. Survival time
      and time to recurrence (disease-free interval [DFI]) were ascertained from
      medical records. Cox proportional hazards regression models were used to estimate
      the hazard ratio (HR) for survival time and DFI in relation to glucose level,
      adjusting for body mass index (BMI), stage, grade, and cytoreduction as
      appropriate. RESULTS: Higher glucose levels were associated with shorter survival
      times in univariate analyses (HR, 1.88; P = .05). Multivariate analysis adjusting
      for stage showed that higher glucose levels were associated with shorter survival
      times (HR, 2.01; P = .04) and DFI (HR, 2.32; P = .05). In the validation set,
      higher glucose levels were associated with shorter survival times (HR, 2.01; P =
      .02) and DFI (HR, 2.48; P = .001) in univariate analysis, although glucose was
      not independent of the effect of cytoreduction when predicting survival time in
      this latter set. CONCLUSIONS: These findings contribute to mounting evidence that
      glucose levels have prognostic value in ovarian carcinoma.

PMID- 19156917
TI  - Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial
      Carcinoma Collaboration.
AB  - BACKGROUND: The literature on upper tract urothelial carcinoma (UTUC) has been
      limited to small, single center studies. A large series of patients treated with
      radical nephroureterectomy for UTUC were studied, and variables associated with
      poor prognosis were identified. METHODS: Data on 1363 patients treated with
      radical nephroureterectomy at 12 academic centers were collected. All pathologic
      slides were re-reviewed by genitourinary pathologists according to strict
      criteria. RESULTS: Pathologic review revealed renal pelvis location (64%),
      necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in
      situ (28.7%), and high-grade disease (63.7%). A total of 590 patients (43.3%)
      underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) 
      positive. Over a mean follow-up of 51 months, 379 (28%) patients experienced
      disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5-year
      recurrence-free and cancer-specific survival probabilities (+/-SD) were 69%+/-1%
      and 73%+/-1%, respectively. On multivariate analysis, high tumor grade (hazards
      ratio [HR]: 2.0, P<.001), advancing pathologic T stage (P-for-trend<.001), LN
      metastases (HR: 1.8, P<.001), infiltrative growth pattern (HR: 1.5, P<.001), and
      LVI (HR: 1.2, P=.041) were associated with disease recurrence. Similarly, patient
      age (HR: 1.1, P=.001), high tumor grade (HR: 1.7, P=.001), increasing pathologic
      T stage (P-for-trend<.001), LN metastases (HR: 1.7, P<.001), sessile architecture
      (HR: 1.5, P=.002), and LVI (HR: 1.4, P=.02) were independently associated with
      cancer-specific survival. CONCLUSIONS: Radical nephroureterectomy provided
      durable local control and cancer-specific survival in patients with localized
      UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI
      were important prognostic variables associated with oncologic outcomes, which
      could potentially be used to select patients for adjuvant systemic therapy.

PMID- 19156918
TI  - Hepatocellular carcinoma with main portal vein tumor thrombus: treatment with 3
      dimensional conformal radiotherapy after portal vein stenting and transarterial
      chemoembolization.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) with main portal vein tumor thrombus
      (MPVTT) is often associated with poor prognosis. We retrospectively assessed the
      effectiveness of percutaneous transhepatic portal vein stenting and transarterial
      chemoembolization (PTPVS-TACE) combined with or without 3-dimensional conformal
      radiotherapy (3-DCRT) for HCC with MPVTT. METHODS: Forty-five patients with HCC
      complicated by MPVTT were treated with PTPVS-TACE. Among them, 16 patients (group
      A) received 3-DCRT with 30-60Gy as daily 2Gy fractions. The remaining 29 patients
      (group B) received no radiotherapy. The tumor responses, complications, stent
      patency rates, and cumulative survival rates were evaluated, and the Kaplan-Meier
      method and log-rank test were used for survival analysis. RESULTS: No severe
      complications were associated with PTPVS-TACE and 3-DCRT. The objective response
      rate (CR and PR) was 35.6%. The 60-, 180-, and 360-day cumulative stent patency
      rates were 93.3%, 62.2%, and 34.6% in group A, and 58.6%, 21.7%, and 10.8% in
      group B, respectively, showing significant difference between the 2 groups
      (P<.01). The mean patency time was 475.20+/-136.97 and 199.58+/-61.40 days,
      respectively. The 60-, 180-, and 360-day cumulative survival rates were 93.8%,
      81.3%, and 32.5%, respectively, for group A, 86.2%, 13.8%, and 6.9%,
      respectively, for group B. Significant statistical differences were detected
      between the 2 groups (P<.01). CONCLUSIONS: These findings suggest that sequential
      therapy by PTPVS-TACE-3-DCRT is possibly an effective treatment modality for HCC
      complicated by main portal vein tumor thrombus.

PMID- 19156919
TI  - Accuracy of clinical evaluation of locally advanced breast cancer in patients
      receiving neoadjuvant chemotherapy.
AB  - BACKGROUND: Physical examination (PE), mammography (MG), breast magnetic
      resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (PET),
      and pathologic evaluation are used to assess primary breast cancer. To the
      authors' knowledge, their accuracy has not been well studied in patients
      receiving neoadjuvant chemotherapy. Accuracies of each modality in tumor and
      lymph node assessment in patients with T3/T4 tumors receiving neoadjuvant
      chemotherapy were compared. METHODS: Forty-five patients of a prospective
      clinical trial studying T3-T4M0 tumors were included. Patients received
      neoadjuvant chemotherapy: docetaxel/carboplatin with or without trastuzumab
      before and/or after surgery (depending on HER-2/neu status and randomization).
      Tumor measurements by PE, MG, and MRI and lymph node status by PE and PET were
      obtained before and after neoadjuvant chemotherapy. Concordance among different
      clinical measurements was assessed and compared with the tumor and lymph node
      staging by pathology. Spearman correlation (r) and root mean square error (RMSE)
      were used to measure the accuracy of measurements among all modalities and
      between modalities and pathologic tumor size. RESULTS: Compared with the tumor
      size measured by PE, MRI was more accurate than MG at baseline (r=0.559,
      RMSE=35.4% vs r=0.046, RMSE=66.1%). After neoadjuvant chemotherapy, PE correlated
      better with pathology than MG or MRI (r=0.655, RMSE=88.6% vs r=0.146, RMSE=147.1%
      and r=0.364, RMSE=92.6%). Axillary lymph node assessment after neoadjuvant
      chemotherapy demonstrated high specificity but low sensitivity by PET and PE.
      CONCLUSIONS: Findings suggested that MRI was a more accurate imaging study at
      baseline for T3/T4 tumor, and PE correlated best with pathology finding. PET and
      PE both correctly predicted positive axillary lymph nodes but not negative lymph
      nodes.

PMID- 19156920
TI  - Computed tomography scan-driven selection of treatment for retroperitoneal
      liposarcoma histologic subtypes.
AB  - BACKGROUND: Well differentiated (WD) and dedifferentiated (DD) retroperitoneal
      liposarcoma (RPLS) have distinct biologic behaviors. Consequently, the
      therapeutic approaches for these tumors differ and mandate an accurate
      preoperative diagnosis. The authors of this report evaluated whether computed
      tomography (CT) can be used to differentiate between WD and DD RPLS. METHODS:
      Imaging studies (CT, magnetic resonance imaging, and positron emission tomography
      CT) from 78 patients with RPLS who underwent surgery at the University of Texas
      M. D. Anderson Cancer Center (UTMDACC) between 2001 and 2007 were reviewed by a
      senior bone and soft tissue sarcoma radiologist who was blinded to the final
      histopathologic diagnosis. A focal nodular/water density area within an RPLS was
      interpreted as a marker suggestive of DD. Correlations between imaging diagnosis,
      histology, and clinical outcome were analyzed. RESULTS: The study radiologist
      identified 60 RPLS as DD and 17 RPLS as WD. A radiologic diagnosis of a WD was
      correlated with preoperative biopsy and postoperative histology in all patients
      (100%). Focal nodular/water density was a very sensitive marker of DD (97.8%);
      however, it had relatively low specificity (51.5%). Sixteen WD RPLS (48.5%)
      contained focal nodular/water density areas, leading to their misdiagnosis as DD;
      half of those tumors had hypercellular WD. Of 78 preoperative biopsies, 22
      (28.2%) were performed at UTMDACC under CT guidance. Preoperative histologic
      diagnoses obtained from 12 biopsies derived from focal nodular/water density
      areas were confirmed as unchanged on final pathology; whereas, in 50% of biopsies
      that were not taken from a suspicious area, DD histology was misdiagnosed as WD.
      CONCLUSIONS: When CT features are suggestive of WD, no further diagnostic tests
      are needed for tumor characterization. Moreover, CT can accurately identify most
      DD, thereby rendering their under-treatment unlikely; however, a CT-guided biopsy
      is needed to differentiate between DD and WD RPLS that contain focal
      nodular/water density areas, thereby avoiding their over treatment.

PMID- 19156925
TI  - Damage mechanisms of suspended animal cells in agitated bioreactors with and
      without bubble entrainment. Biotechnol Bioeng 1990; 36:476-83.

PMID- 19156926
TI  - O(6)-methylguanine DNA methyltransferase immunoexpression in nonfunctioning
      pituitary adenomas: are progressive tumors potential candidates for temozolomide
      treatment?
AB  - BACKGROUND: Currently, no effective alternative treatment exists for progressive,
      regrowing, nonfunctioning pituitary adenomas (NFPA) that are resistant to
      conventional multimodality therapy. Temozolomide (TMZ) was proposed as a
      treatment option for pituitary carcinomas and aggressive pituitary adenomas.
      Recently, it was suggested that the responsiveness of pituitary tumors to TMZ
      depends on the immunoexpression of O(6)-methylguanine DNA methyltransferase
      (MGMT). Therefore, the authors of this report assessed MGMT expression in a
      series of patients with progressive, regrowing NFPAs to evaluate whether TMZ may
      serve as alternative treatment option. METHODS: On the basis of postoperative
      magnetic resonance imaging, 45 patients with NFPAs were allocated to either a
      group with progressive, regrowing tumors (n = 24) or a tumor-free group (n = 21),
      which served as a control. MGMT expression was assessed semiquantitatively by
      immunohistochemistry (low expression was defined as <or=50% immunostained adenoma
      cells, and high expression was defined as >50% immunostained adenoma cells) and
      was compared between the 2 groups. RESULTS: At the time of initial surgery, low
      MGMT expression was observed in 12 of 24 patients (50%) in the study group with
      progressive, regrowing NFPAs. In the control group of tumor-free patients, only 5
      of 21 patients (24%) exhibited low MGMT expression. A comparable distribution of
      MGMT expression was observed in the specimens from repeat surgeries. A shorter
      interval to second surgery was observed in patients who had low MGMT expression.
      CONCLUSIONS: The current data has suggested that half of the patients with
      progressive, regrowing NFPAs exhibit low MGMT expression and are potential
      candidates for treatment with TMZ. These findings provide a rationale for the use
      of TMZ as an alternative treatment approach in this subgroup if conventional
      therapy, including reoperation, radiosurgery, and radiotherapy, fails.

PMID- 19156927
TI  - The prognostic value of pretreatment CA 125 in patients with advanced ovarian
      carcinoma: a Gynecologic Oncology Group study.
AB  - BACKGROUND: The objective of the current study was to determine the prognostic
      significance of a pretreatment serum CA 125 level in patients with advanced
      epithelial ovarian carcinoma (EOC) who received treatment with a standard
      chemotherapy regimen. METHODS: Patients with International Federation of
      Gynecology and Obstetrics stage III/IV ovarian carcinoma who were on 1 of 7
      Gynecologic Oncology Group (GOG) phase 3 trials and received treatment with a
      standard regimen of intravenous cisplatin and paclitaxel were included. A Cox
      regression model was used to assess the impact of CA 125 levels drawn before the
      initiation of chemotherapy on progression-free survival (PFS) both overall and by
      subgroup, including surgical debulking status, disease stage, and histologic
      subtype. RESULTS: In total, 1,299 patients who were on the cisplatin/paclitaxel
      arms of the GOG trials were eligible. The median CA 125 level was 246 U/mL. Only
      7.6% of patients had a normal CA 125 level (<or=35 U/mL). The lowest median CA
      125 level was observed in the group with mucinous tumors; however, 69% of women
      who had mucinous tumors had abnormal CA 125 levels. Shorter PFS was observed with
      increasing CA 125 and persisted in multivariate analysis. Overall and in the
      serous subgroup, a 1-fold increase in CA 125 level was associated with a 7%
      increase in the hazard of disease progression (P < .001). This association was
      even more pronounced in patients who had stage III disease that was debulked to
      microscopic disease (15%; P = .003) and in patients who had endometrioid tumors
      (17%; P = .001). CONCLUSIONS: A normal CA 125 level in the setting of advanced
      EOC was rare even after surgical debulking. The pretreatment CA 125 level was an
      independent predictor of PFS in patients with advanced EOC who received a
      standard chemotherapy regimen, particularly in the setting of disease that was
      debulked to a microscopic residual and in the serous or endometrioid subtypes.

PMID- 19156928
TI  - Preoperative and postoperative nomograms incorporating surgeon experience for
      clinically localized prostate cancer.
AB  - BACKGROUND: Accurate preoperative and postoperative risk assessment has been
      critical for counseling patients regarding radical prostatectomy for clinically
      localized prostate cancer. In addition to other treatment modalities, neoadjuvant
      or adjuvant therapies have been considered. The growing literature suggested that
      the experience of the surgeon may affect the risk of prostate cancer recurrence.
      The purpose of this study was to develop and internally validate nomograms to
      predict the probability of recurrence, both preoperatively and postoperatively,
      with adjustment for standard parameters plus surgeon experience. METHODS: The
      study cohort included 7,724 eligible prostate cancer patients treated with
      radical prostatectomy by 1 of 72 surgeons. For each patient, surgeon experience
      was coded as the total number of cases conducted by the surgeon before the
      patient's operation. Multivariable Cox proportional hazards regression models
      were developed to predict recurrence. Discrimination and calibration of the
      models was assessed following bootstrapping methods, and the models were
      presented as nomograms. RESULTS: In this combined series, the 10-year probability
      of recurrence was 23.9%. The nomograms were quite discriminating (preoperative
      concordance index, 0.767; postoperative concordance index, 0.812). Calibration
      appeared to be very good for each. Surgeon experience seemed to have a quite
      modest effect, especially postoperatively. CONCLUSIONS: Nomograms have been
      developed that consider the surgeon's experience as a predictor. The tools
      appeared to predict reasonably well but were somewhat little improved with the
      addition of surgeon experience as a predictor variable.

PMID- 19156930
TI  - Binding of imipramine, dosulepin, and opipramol to liposomes for overdose
      treatment.
AB  - Polymer shielded liposomes were investigated as detoxifying agents for the weak
      bases imipramine and dosulepin and the diprotic drug opipramol. In vitro binding
      measurements in the presence of human serum samples revealed that the liposomes
      reduced the free drug concentration of the weak bases (corrected for protein
      binding) by 88-93%. The reduction for opipramol was around 76%. The results
      demonstrate that polymer shielded liposomes composed of anionic lipids are widely
      useful for drug overdose treatment. Polyethylene glycol chain lengths of 2000 and
      5000 for the polymer coatings were also explored, and chain length showed no
      evidence of affecting drug uptake by liposomes. Liposomes compete favorably with
      other binding targets for drugs, and pharmacokinetic considerations suggest that
      liposomes could reduce toxicity by transporting drugs from fast-equilibrating
      organs such as the heart to slow-equilibrating organs such as the fat, muscle,
      and skin.

PMID- 19156929
TI  - Locoregional recurrence of triple-negative breast cancer after breast-conserving
      surgery and radiation.
AB  - BACKGROUND: The results of radiation on the local control of triple receptor
      negative breast cancer (negative estrogen [ER], progesterone [PR], and HER-2/neu
      receptors) was studied. METHODS: Conservative surgery and radiation were used in
      753 patients with T1-T2 breast cancer. Three groups were defined by receptor
      status: Group 1: ER or PR (+); Group 2: ER and PR (-) but HER-2 (+); and Group 3:
      triple-negative (TN). Factors analyzed were age, menopausal status, race, stage,
      tumor size, lymph node status, presentation, grade, extensive in situ disease,
      margins, and systemic therapy. The primary endpoint was 5-year locoregional
      recurrence (LRR) isolated or total with distant metastases. RESULTS: ER- and PR
      negative patients were statistically significantly more likely to be black, have
      T2 disease, have tumors detectable on both mammography and physical examination,
      have grade 3 tumors, and receive chemotherapy. There were no significant
      differences noted with regard to ER- and PR- patients by HER-2 status. There was
      a significant difference noted in rates of first distant metastases (3%, 12%, and
      7% for Groups 1, 2, and 3, respectively; P = .009). However, the isolated 5-year
      LRR was not significantly different (2.3%, 4.6%, and 3.2%, respectively; P = .36)
      between the 3 groups. CONCLUSIONS: Patients with TN breast cancer do not appear
      to be at a significantly increased risk for isolated LRR at 5 years and therefore
      remain appropriate candidates for breast conservation.

PMID- 19156932
TI  - Lessons from the TAPS study - warfarin: a major cause of threats to patients
      safety.

PMID- 19156931
TI  - Pharmacodynamics of glucose regulation by methylprednisolone. I. Adrenalectomized
      rats.
AB  - Mechanisms related to the adverse effects of corticosteroids on glucose
      homeostasis were studied. Five groups of adrenalectomized (ADX) rats were given
      methylprednisolone (MPL) intravenously at 10 and 50 mg/kg, or a continuous 7 day
      infusion at rates of 0, 0.1, 0.3 mg/kg/h via subcutaneously implanted Alzet mini
      pumps. Plasma concentrations of MPL, glucose and insulin were determined at
      various time points up to 72 h after injection or 336 h after infusion. The
      pharmacokinetics of MPL was captured with a two-compartment model. The Adapt II
      software was used in modeling. Injection of MPL caused a temporary glucose
      increase over 6 h by stimulating gluconeogenesis. The glucose changes stimulated
      pancreatic beta-cell secretion yielding a later insulin peak at around 10 h. In
      turn, insulin can stimulate glucose disposition. However, long-term MPL treatment
      caused continuous hyperglycemia during and after infusion. Insulin was increased
      during infusion, and immediately returned to baseline after the infusion was
      terminated, despite the almost doubled glucose concentration. A disease
      progression model incorporating the reduced endogenous glucose disposition was
      included to capture glucose homeostasis under different treatments. The results
      exemplify the importance of the steroid dosing regimen in mediating
      pharmacological and adverse metabolic effects. This mechanistic
      pharmacokinetic/pharmacodynamic (PK/PD) model quantitatively describes the
      induction of hyperglycemia and provides additional insights into metabolic
      disorders such as diabetes.

PMID- 19156933
TI  - An accurate confirmation of human immunodeficiency virus type 1 (HIV-1) and 2
      (HIV-2) infections with a dot blot assay using recombinant p24, gp41, gp120 and
      gp36 antigens.

PMID- 19156934
TI  - From the editors. The legacy of the theory of natural selection.

PMID- 19156936
TI  - Flory: tariff will be right not rushed.

PMID- 19156935
TI  - A few too many: is there hope for the hung over?

PMID- 19156937
TI  - Trusts must clean up in fear of harsh penalties.

PMID- 19156938
TI  - Noel Plumridge on CQUIN's sparkle.

PMID- 19156939
TI  - Pharmacy's perfect prescription.

PMID- 19156940
TI  - Data briefing. Cut short stays to lower admissions.

PMID- 19156941
TI  - Recession. When good times turn bad.
AB  - The 1973-74 recession meant the government was forced to cut public spending and
      a hospital building programme was curtailed. In the 1990s there was "desperation"
      in the health service at being under-resourced. Managers today are advised to
      prepare now for lower resources, although improved financial management should
      mean the NHS is better able to cope than in previous years.

PMID- 19156942
TI  - Service redesign. Real lessons of Ethel the unreal.

PMID- 19156943
TI  - Efficiency. Put a lid on it.

PMID- 19156944
TI  - Specialist diabetes services and acute-general internal medicine.

PMID- 19156945
TI  - Trends in hospital admissions for pulmonary embolism.

PMID- 19156946
TI  - Inflammatory rheumatic conditions and cardiovascular disease.

PMID- 19156947
TI  - [Do you have to fire a coworker? A notice of termination should not come out of
      the clear sky].

PMID- 19156948
TI  - [Treatment of ulcus cruris and other chronic wounds. Waiting can cost the foot].

PMID- 19156949
TI  - [Nocturnal shortness of breath: in asthma look for reflux -- is it worthwhile?].

PMID- 19156950
TI  - [Nobel Prize conferring to Professor H. zur Hausen. Recognition of the one
      frequently met with hostility].

PMID- 19156951
TI  - [Suspected meningitis: you have to treat fast now!].

PMID- 19156952
TI  - [Disorders in the regulation of alertness. Drowsy white rock climbing and wide
      awake at night].

PMID- 19156953
TI  - [Always tired--what is behind it?].

PMID- 19156954
TI  - [Falling sleep inopportunely: treatment of narcolepsy].

PMID- 19156955
TI  - [Minor foot curses (10): tarsal tunnel syndrome].

PMID- 19156956
TI  - [Low-dose strong opioid (LDSO)--treatment of pain in osteoarthritis].

PMID- 19156957
TI  - [Near-death experiences: a review of the thesis of pathoclisis, neurotransmitter
      abnormalities, and psychological aspects].

PMID- 19156958
TI  - [Hip prothesis and sexuality. What is when recommended?].

PMID- 19156959
TI  - [Therapy of chronic inflammatory bowel diseases. TNF-alpha blocker in Crohn
      disease: earlier use is rewarding].

PMID- 19156960
TI  - National action on violence.

PMID- 19156961
TI  - Challenges of detention.

PMID- 19156962
TI  - Nurses can bring change.

PMID- 19156963
TI  - Nurses lead the way.

PMID- 19156964
TI  - Police must act.

PMID- 19156965
TI  - Self worth the key.

PMID- 19156966
TI  - EN training farce.

PMID- 19156967
TI  - Proceedings of the 5th Ferring International Paediatric Endocrinology Symposium,
      Baveno, Italy, 2008.

PMID- 19156968
TI  - [Fritz Hartmann (1920-2007)].

PMID- 19156969
TI  - On: Hall S, Lewith G, Brien S, Little P: A review of the literature in applied
      and specialised kinesiology. Forsch Komplementmed 2008;15:40-46.
AB  - We commend the authors for attempting an in-depth literature review of such a
      diverse field as Specialised Kinesiology. Their recommendations for the tools
      that can be used in methods of analysis in future studies are well advised. The
      title of their paper, however, suffers from design flaws and is deceptive. This
      paper is primarily a review of Touch for Health Kinesiology and its family of
      techniques, which should be distinctly differentiated from Applied Kinesiology as
      defined by the International College of Applied Kinesiology.

PMID- 19156970
TI  - [Dietary Intervention Randomized Controlled Trial (DIRECT) group: weight loss
      with a low-carbohydrate, Mediterranean, or low-fat diet].

PMID- 19156971
TI  - [Evidence-informed management of chronic low back pain with spinal manipulation
      and mobilization].

PMID- 19156972
TI  - [A randomized trial of arthroscopic surgery for osteoarthritis of the knee].

PMID- 19156973
TI  - Pharmacodynamic modelling of rocuronium in adolescents with Duchenne muscular
      dystrophy.
AB  - BACKGROUND AND OBJECTIVE: Studies with rocuronium showed a delayed onset and
      prolonged recovery in patients with Duchenne muscular dystrophy (DMD). The
      objective of this study was to identify the pharmacokinetic and/or
      pharmacodynamic origin of these alterations. METHODS: Twenty-five male patients
      (15 with DMD, 10 controls, aged 10-18 years) were studied. Patients were
      anaesthetized with propofol and sufentanil. Neuromuscular transmission was
      monitored by acceleromyography. Patients received a single intravenous dose of
      0.3 mg kg(-1) rocuronium. In five patients of the DMD group, pharmacokinetic
      modelling was performed from arterial rocuronium concentrations. The time course
      of neuromuscular block was analysed with a sigmoid E(max) model including an
      effect compartment. RESULTS: The pharmacokinetics of rocuronium in DMD patients
      were Vc 63 +/- 14 ml kg(-1), Cl 3.0 +/- 1.0 ml min(-1) kg(-1), half-lives 2.0 +/-
      0.6, 20 +/- 10 and 129 +/- 98 min, SE. For both the DMD and the control group,
      the time course of neuromuscular block could be described by a sigmoid E(max)
      model using the estimated pharmacokinetic parameters of the DMD group. In
      patients with DMD, the equilibration between the central and effect compartment
      was significantly slower (T(1/2)ke0: 9.7 +/- 0.3 vs. 1.3 +/- 0.1 min) and the
      EC(50) was significantly smaller (512 +/- 20 vs. 1170 +/- 64 ng ml(-1)), whereas
      the ED(50) was 0.16 +/- 0.02 mg kg(-1) in both groups. CONCLUSION: The
      pharmacodynamics of rocuronium were significantly altered in patients with DMD,
      whereas the pharmacokinetics seemed to be similar to those in healthy adults.
      Patients with DMD were more sensitive with respect to effect site concentration
      but not with respect to dose.

PMID- 19156974
TI  - [Patient perspective on physicians' dressing].

PMID- 19156976
TI  - ["Don Juan physicians"].

PMID- 19156975
TI  - [Gardasil vaccine and atopic eczema].

PMID- 19156978
TI  - [On space and identity].

PMID- 19156979
TI  - The barracuda's tale: trawlers, the informal sector and a state of classificatory
      disorder off the Nigerian coast.

PMID- 19156980
TI  - The death of a child in old Polish culture.

PMID- 19156982
TI  - The shaping of the personality of peasant youth and its start in life in central
      Poland, 1864-1939.

PMID- 19156983
TI  - The upbringing of children in the light of old Polish pedagogical theory.

PMID- 19156984
TI  - Neuroimaging in vision science. Special issue introduction.

PMID- 19156985
TI  - The diagnosis of art: Van Gogh  and male pattern baldness.

PMID- 19156986
TI  - Anticipatory pursuit is influenced by a concurrent  timing task.
AB  - The ability to predict upcoming events is important to compensate for relatively
      long sensory-motor delays. When stimuli are temporally regular, their prediction
      depends on a representation of elapsed time. However, it is well known that the
      allocation of attention to the timing of an upcoming event alters this
      representation. The role of attention on the temporal processing component of
      prediction was investigated in a visual smooth pursuit task that was performed
      either in isolation or concurrently with a manual response task. Subjects used
      smooth pursuit eye movements to accurately track a moving target after a constant
      duration delay interval. In the manual response task, subjects had to estimate
      the instant of target motion onset by pressing a button. The onset of
      anticipatory pursuit eye movements was used to quantify the subject's estimate of
      elapsed time. We found that onset times were delayed significantly in the
      presence of the concurrent manual task relative to the pursuit task in isolation.
      There was also a correlation between the oculomotor and manual response
      latencies. In the framework of Scalar Timing Theory, the results are consistent
      with a centralized attentional gating mechanism that allocates clock resources
      between smooth pursuit preparation and the parallel timing task.

PMID- 19156987
TI  - Progresses in the implementation of policies and actions in the field of
      disability and mental health.

PMID- 19156988
TI  - [Various problems related to hospital infections and their management].

PMID- 19156989
TI  - [Changes in hospital infections].

PMID- 19156990
TI  - [Prevention of in-hospital infection by drug-resistant organisms].

PMID- 19156991
TI  - [Infections and their management in special wards. 1. Newborn infants' ward].

PMID- 19156992
TI  - [Infections at a special unit and their management. 2. ICU].

PMID- 19156993
TI  - [Infection in specific hospital units and their management. 3. Facilities for
      aged patients].

PMID- 19156995
TI  - [Hospital infections by specific organisms and their management. 2.
      Staphylococcus epidermidis].

PMID- 19156994
TI  - [Hospital infections with specific pathogens and their management. 1. MRSA].

PMID- 19156996
TI  - GPOs say higher prices on the way in 2009.

PMID- 19156997
TI  - Old debate on GPO value won't go away. Annual group purchasing event shows value
      proposition question remains unsettled.

PMID- 19156998
TI  - Up-and-down surgical pack segment posts price rise. Hard-to-track market segment
      subject to vagaries of hospitals and vendors.

PMID- 19156999
TI  - Manage your contracts before they manage you. Step one: Conduct damage
      assessment.

PMID- 19157000
TI  - GPOs turning brighter shade of green. Move toward environmentally preferred
      purchasing fast gaining favor.

PMID- 19157001
TI  - Clinicopathological features of medulloblastoma: an overview with an emphasis on
      molecular biology.
AB  - Medulloblastoma is a malignant, invasive embryonal tumor of the cerebellum with
      preferential manifestation in children, predominantly neuronal differentiation
      and an inherent tendency to metastasize via CSF pathways. In this review we
      present an overview of the clinicopathological aspects of medulloblastoma and the
      recent developments in the biology and genetics of these embryonal brain tumors.
      Increased knowledge of the signaling pathways that play a role in normal
      cerebellum development and tumor formation may lead to new therapeutic approaches
      resulting in a higher cure rate and a better quality of life of medulloblastoma
      patients.

PMID- 19157002
TI  - Infiltrative chordoid meningioma of the pineal region: a study of 2 cases.
AB  - OBJECTIVE: Meningiomas involving the pineal region are rare. Herein we describe
      two cases of chordoid meningioma with histologic evidence of pineal gland
      infiltration. MATERIALS AND METHODS: Clinical histories were abstracted from
      chart review and consultation letters. HE-stained slides were reviewed in both
      cases. Selected immunohistochemical stains were performed. RESULTS: the patients
      included a 44-year-old male and a 37-year-old female who presented with symptoms
      of intracranial tumor referable to the pineal region. On magnetic resonance
      imaging (MRI), both lesions demonstrated heterogeneous contrast enhancement.
      Histologically, the tumors were characterized by strands and cords
      ofmeningothelial cells arranged in a mucinous stroma. In addition, obvious
      meningothelial cytology as well as focal osseous metaplasia (Case 1), and
      transitional histology (Case 2) were also noted. Tumor cells demonstrated EMA and
      focal S100 protein immunoreactivity, but lacked cytokeratin AE1/AE3 and glial
      fibrillary acidic protein (GFAP) staining. Synaptophysin and neurofilament
      protein highlighted the overrun pineal gland parenchyma. MIB1-proliferative index
      was 8.4 and 20.1%, respectively. CONCLUSIONS: Chordoid meningioma, although rare,
      may occur in the pineal region. The differential diagnosis of this meningioma
      subtype in this location is discussed.

PMID- 19157003
TI  - Papillary glioneuronal tumor: not always a benign tumor?
AB  - Papillary glioneuronal tumor (PGNT) is a variant of ganglioglioma, characterized
      by a pseudopapillary structure with a single pseudostratified layer of small,
      cuboidal, GFAP-positive cells around hyalinized blood vessels. To date, less than
      30 cases have been described with a usually benign course. We report two
      additional cases: a clinically, radiologically and histopathologically typical
      tumor in a 38-year-old man and an atypical tumor with histopathological features
      of anaplasia in a 74-year-old woman. The latter tumor showed the classical
      pseudopapillary pattern with ganglioid cells and some astrocytes between the
      papillae, but also had changes suggestive of anaplasia including necrosis,
      capillary endothelial proliferation, mitoses, dedifferentiation with loss of GFAP
      expression of the cuboidal cells and increased Ki-67 labeling of over 10%. Only
      one other case with increased proliferative activity in a minigemistocytic
      component has previously been described. Our cases indicate that PGNT type of
      ganglioglioma can have a spectrum of anaplastic changes of higher grade.

PMID- 19157004
TI  - Benign cylindroma causing transcalvarial invasion in a patient with familial
      cylindromatosis.
AB  - OBJECTIVE: To describe a case of scalp cylindroma without features of malignancy
      invading through the skull and dura, and producing massive intracranial
      extension. Tumors of epidermis and epidermal appendages rarely show bony
      invasion, but invasive tendency in some tumor types has been associated with
      increased TP53 expression. PATIENT AND METHODS: Patient with familial
      cyindromatosis (Brooke-Spiegler syndrome) who had undergone numerous previous
      surgical excisions over the past 30 years of his scalp cylindromas. Light
      microscopic and immunohistochemical characterization of resected tumor, with TP53
      immunostaining in the invasive tumor was compared with that seen in five other
      cutaneous, non-invasive cylindromas. RESULTS: Tumor showed no increase in mitotic
      rate or increased immunostaining for TP53. CONCLUSION: Multiple previous
      surgeries down to pericranium may have contributed to local weakening of tissues
      and facilitated transcalvarial invasion. While an uncommon occurrence, both
      benign and malignant cylindromas have the capacity to invade bone, particularly
      in patients with the familial syndrome.

PMID- 19157005
TI  - The role of redox in signal transduction.
AB  - Functioning and efficient cell signaling is vital for the survival of cells. Over
      the course of many years, various components have been identified and recognized
      as crucial for the transduction of signals in cells. Many of the mechanisms allow
      for a relatively rapid switching of signals, on or off, with common examples
      being the G proteins and protein phosphorylation. However, recently it has become
      apparent that other modifications of amino acids are also important, including
      reactions with nitric oxide, for example, S-nitrosylation, and of particular
      relevance here, oxidation of cysteine residues. Such oxidation will be dependent
      on the redox status of the intracellular environment in which that protein
      resides, and this will in turn be dictated by the presence of pro-oxidants and
      antioxidants. Here, the chemistry ofredox modification of amino acids is
      introduced, and a general overview of the role ofredox in mediating signal
      transduction is given.

PMID- 19157006
TI  - The measurement of nitric oxide and its metabolites in biological samples by
      ozone-based chemiluminescence.
AB  - A plethora of publications on techniques and methodologies for measuring nitric
      oxide (NO) or reaction products of NO (NO metabolites) has served in recent years
      to complicate and confuse the majority of researchers interested in this field.
      Here, we provide a practical approach and summarize the key issues and
      corresponding solutions regarding quantification with the use of ozone-based
      chemiluminescence, which is the most accurate, sensitive, and widely used NO
      detection method. We have drawn on the vast experience of leaders in the field to
      produce this consensus, but the views and implications presented herein represent
      our own, and we limit our advice to those techniques with which we have direct
      experience. Hopefully, this guide will allow authors to make more informed
      decisions regarding NO metabolite measurement methodology, without the need for
      each subsequent group to rediscover previously observed advantages and pitfalls.

PMID- 19157007
TI  - Detection and measurement of reactive oxygen intermediates in mitochondria and
      cells.
AB  - Reactive oxygen intermediates (ROIs) play a key role in a number of human
      diseases either by inducing cell death, cellular proliferation, or by acting as
      mediators in cellular signaling. Therefore, their measurement in vivo and in cell
      culture is desirable but technically difficult and often troublesome. To address
      some of the key methodological issues in examining the formation of ROI in cells
      and mitochondria, this chapter discusses the following: (a) the cellular sources
      of ROI and their enzymatic removal, (b) common methods used to determine cellular
      and mitochondrial ROI such as chemiluminescence, electron paramagnetic resonance
      spectroscopy, fluorescence, and enzymatic techniques, and (c) some common
      problems associated with these assays and the interpretation of data. We also
      provide some simple protocols for the estimation of ROI production in cells and
      mitochondria, and when measuring ROI in cells and mitochondria, we emphasize the
      need for thorough understanding of results obtained and their interpretation.

PMID- 19157008
TI  - Redox-sensitive green fluorescent protein: probes for dynamic intracellular redox
      responses. A review.
AB  - The quantification of transient redox events within subcellular compartments,
      such as those involved in certain signal transduction pathways, requires specific
      probes with high spatial and temporal resolution. Redox-sensitive variants of the
      green fluorescent protein (roGFP) have recently been developed that allow the
      noninvasive monitoring ofintracellular thiol-disulfide equilibria. In this
      chapter, the biophysical properties of these probes are discussed, including
      recent efforts to enhance their response times. Several recent applications of
      roGFPs are highlighted, including roGFP expression within Arabidopsis to monitor
      redox status during root elongation, expression in neurons to measure oxidative
      stress during ischemia, and targeting of roGFPs to endosomal compartments
      demonstrating unexpectedly oxidizing potentials within these compartments.
      Possible future directions for the optimization of roGFPs or new classes of redox
      sensitive fluorescent probes are also discussed.

PMID- 19157009
TI  - Measuring redox changes in vivo in leaves: prospects and technical challenges.
AB  - In leaves, the functioning of many key proteins under conditions promoting
      oxidative stress depends to a large extent on the redox potential of the
      glutathione couple. Routine measurements of the glutathione pool in leaves are
      destructive and labor-intensive processes that tend to underestimate the redox
      state. Therefore, a challenge for plant scientists is to develop a tool capable
      of measuring the redox state of the glutathione couple spatially (at different
      levels of resolution) and temporally in tissues and subcellular compartments in
      vivo. This chapter highlights the possibilities of using redox-sensitive green
      fluorescence proteins (roGFPs) as real-time redox reporters for use in intact
      plants and focuses on practical assessments of using such bioindicators in
      different leaf cell types subjected to environmental change. The advantages and
      shortcomings of different GFP variants are discussed along with the choice of
      system for leaves and possible approaches to overcoming some of the problems. We
      consider roGFP1-12 as an ideal candidate for developing a redox reporter system
      in whole plants because it has several advantages over the other variants, with
      dual excitation peaks allowing a ratiometric approach, insensitivity to pH and
      halide ions, increased response times for real-time measurements, and appropriate
      emission wavelengths for use in leaves. We conclude that when using roGFP1-12
      with specific cell promotors, it would be possible to target distinct cell
      compartments and tissues and monitor changes in glutathione redox state to
      determine the effects of reactive oxygen species on specific cellular components.

PMID- 19157010
TI  - Imaging of intracellular hydrogen peroxide production with HyPer upon stimulation
      of HeLa cells with epidermal growth factor.
AB  - Reactive oxygen species (ROS) regulate both normal cell functions by activating a
      number of enzymatic cascades and pathological processes in many diseases by
      inducing oxidative stress. For many years since the discovery of ROS in
      biological systems, there were no adequate methods of detection and
      quantification of these molecules inside the living cells. We developed the first
      genetically encoded fluorescent indicator for the intracellular detection of
      hydrogen peroxide, HyPer, that can be used for imaging of H2O2 production by
      cells under various physiological and pathological conditions. Unlike most known
      ROS indicators, HyPer allows the generation of a real-time image series that give
      precise information about the time course and intensity of H2O2 changes in any
      compartment of interest. In this chapter, we describe the method of confocal
      imaging of hydrogen peroxide production in HeLa cells upon stimulation with
      epidermal growth factor. The technique described may be accepted with minimal
      variations for the use in other cell lines upon various conditions leading to
      H2O2, production.

PMID- 19157011
TI  - Tools to investigate reaction oxygen species-sensitive signaling proteins.
AB  - The thiol groups ofcysteine residues on proteins are attractive oxidative targets
      for modification by reactive oxygen species, such as hydrogen peroxide (H2O2).
      Such modification can lead to important cellular signaling processes that
      ultimately result in modification of the physiology of the organism. To identify
      such proteins that are amenable to oxidative modification, different methods can
      be used. Here, two such approaches are described: one being the use of
      fluorescent thiol derivatives, and the second being the use of genetic mutants
      that are mutated in thiol residues. Using the model plant Arabidopsis thaliana,
      cell cultures, and whole plants, we describe these tools to help the reader
      understand the function of such thiol modifications on plant responses.

PMID- 19157012
TI  - Methods for preparing crystals of reversibly oxidized proteins: crystallization
      of protein tyrosine phosphatase 1B as an example.
AB  - Regulation of protein activity through the oxidation and reduction of cysteines
      is emerging as an important mechanism in the control of cell-signaling pathways.
      Protein tyrosine phosphatase 1B (PTP1B), for example, is reversibly inhibited by
      oxidation at the catalytic cysteine in response to stimulation of cells by
      insulin or epidermal growth factor. We have conducted structural studies on the
      redox regulation of PTP1B and have demonstrated that the oxidation of the
      catalytic cysteine results in the formation of a bond between the sulfur atom of
      the catalytic cysteine and the amide nitrogen of the neighboring serine. This
      bond, referred to here as a sulfenamide bond, is reversible upon the addition of
      glutathione, indicating that this sulfenamide intermediate could function within
      signaling pathways to protect the cysteine from overoxidation to less readily
      reducible states. Formation of the sulfenamide bond is accompanied by changes in
      the tertiary structure at the catalytic site, and these changes may be important
      for additional regulation of the enzyme. Here, we present methods for preparing
      crystals ofPTP1B with a sulfenamide bond at the catalytic cysteine. The methods
      may be adaptable for other proteins that are subject to redox regulation.

PMID- 19157013
TI  - Methods for the study of redox-mediated changes in p53 structure and function.
AB  - It is now generally accepted that both the structure and function of a number of
      specific transcriptional factors, including p53, are subject to redox regulation
      in cells in which these factors are expressed. The present chapter describes
      methods for the analysis of redox changes in the structure of p53 and the effect
      of redox modulation on binding of p53 to a DNA consensus sequence. In addition,
      methods are described for studying the effect of redox perturbations of cells on
      the functioning of p53 in the cell cycle and in apoptosis. By studying the effect
      ofredox agents on p53, we have concluded that p53 is subject to structural redox
      modulation and that this modulation affects the functional ability of the protein
      to bind to DNA, to cause cell cycle arrest, and to trigger apoptosis.

PMID- 19157014
TI  - Redox regulation and trapping sulfenic acid in the peroxide-sensitive human
      mitochondrial branched chain aminotransferase.
AB  - The human branched chain aminotransferase enzymes are key regulators of glutamate
      metabolism in the brain and are among a growing number of redox-sensitive
      proteins. Studies that use thiol-specific reagents and electrospray ionization
      mass spectrometry demonstrate that the mitochondrial BCAT enzyme has a redox
      active CXXC center, which on oxidation forms a disulfide bond (RSSR), via a
      cysteine sulfenic acid intermediate. Mechanistic details of this redox regulation
      were revealed by the use of mass spectrometry and dimedone modification. We
      discovered that the thiol group at position C315 of the CXXC motif acts a redox
      sensor, whereas the thiol group at position C318 permits reversible regulation by
      forming an intrasubunit disulphide bond. Because of their roles in redox
      regulation and catalysis, there is a growing interest in cysteine sulphenic
      acids. Therefore, development of chemical tags/methods to trap these transient
      intermediates is of immense importance.

PMID- 19157015
TI  - Detection of carbonylated proteins in two-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis separations.
AB  - Protein carbonyls are an index of protein oxidation which, in turn, reflects the
      interplay of oxidative stress and degradation of oxidatively modified proteins.
      Protein carbonyls are increased in brain proteins in aging and age-related
      neurodegenerative disorders, including Alzheimer's disease. In this chapter, we
      outline methods to detect protein carbonyls following two dimensional-based
      separation of brain proteins.

PMID- 19157016
TI  - Analysis of global and specific changes in the disulfide proteome using redox two
      dimensional polyacrylamide gel electrophoresis.
AB  - Protein cysteine sulfhydryl groups are susceptible to a number of redox-dependent
      modifications, including an interchange between the reduced sulfhydryl and an
      oxidized disulfide state. A growing body of evidence suggests that reversible
      disulfide bond formation alters the structure and function of proteins. In this
      chapter, a method is described for isolating disulfide bonded proteins from
      different subcellular compartments by using a differential detergent
      fractionation technique followed by sequential nonreducing/reducing two
      dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (i.e.,
      Redox 2D-PAGE). This method can be adapted to examine individual redox-active
      proteins by immunoprecipitating an epitope-tagged redox protein expressed in
      cultured cells and using Redox 2D-PAGE and mass spectrometry to identify proteins
      that form mixed disulfides with the tagged protein. With the use of these
      techniques, it is shown that disulfide bond formation occurs within families of
      cytoplasmic proteins and may provide a common mechanism used to control multiple
      physiological processes.

PMID- 19157017
TI  - Protein-thiol oxidation, from single proteins to proteome-wide analyses.
AB  - Protein-thiol oxidation subserves multiple biological functions, from enzymatic
      catalysis to protein oxidative folding, protein trafficking, reactive oxygen
      (ROS) and nitrogen (RNS) species sensing and signaling and, more generally,
      protein redox regulation. Protein-thiol oxidation may also constitute a sequel of
      ROS and RNS toxicity. Accurate and robust methods aimed at monitoring the in vivo
      redox state of cysteine residues are thus warranted. To this aim, we have
      developed biochemical approaches that rely on trapping cysteine residues in their
      in vivo redox state using acidic conditions, followed by the differential
      labeling of reduced versus oxidized cysteine residues by thiol-specific reagents.
      These methods have been instrumental in the discovery of eukaryotic peroxide
      receptors and new ROS-scavenging enzymes and in identifying the repertoire of
      cytoplasmic oxidized protein thiols. Proteome-wide approaches also contributed to
      establish the functions of the thioredoxin and glutathione pathways in eukaryotic
      cytoplasmic thiol-redox control.

PMID- 19157018
TI  - Analysis of redox relationships in the plant cell cycle: determinations of
      ascorbate, glutathione and poly (ADPribose)polymerase (PARP) in plant cell
      cultures.
AB  - Reactive oxygen species (ROS) and low molecular weight antioxidants, such as
      glutathione and ascorbate, are powerful signaling molecules that participate in
      the control of plant growth and development, and modulate progression through the
      mitotic cell cycle. Enhanced reactive oxygen species accumulation or low levels
      of ascorbate or glutathione cause the cell cycle to arrest and halt progression
      especially through the G1 checkpoint. Plant cell suspension cultures have proved
      to be particularly useful tools for the study of cell cycle regulation. Here we
      provide effective and accurate methods for the measurement of changes in the
      cellular ascorbate and glutathione pools and the activities of related enzymes
      such poly (ADP-ribose) polymerase during mitosis and cell expansion, particularly
      in cell suspension cultures. These methods can be used in studies seeking to
      improve current understanding of the roles of redox controls on cell division and
      cell expansion.

PMID- 19157019
TI  - Generation and detection of S-nitrosothiols.
AB  - Nitric oxide (NO) plays a pivotal role in cellular signaling in many different
      organisms as the result of the modification of protein activities/functions by
      protein S-nitrosylation. This NO-dependent posttranslational modification is
      based on the attachment of NO to the sulfur moiety of cysteine residues. However,
      the instability of S-nitrosothiols makes it difficult to analyze this type of
      protein modification in vitro as well as in vivo. Jeffrey and colleagues
      developed a method--named the biotin switch method--that allows the detection and
      purification of S-nitrosylated proteins. The principle behind this technology is
      the substitution of the NO group by a biotin linker in a three-step procedure.
      First, the all free thiol groups are blocked with a thiol-reactive agent,
      followed by selective reduction of the S-nitrosylated cysteine residues using
      ascorbate. In the final step, the reduced thiol groups are labeled with a biotin
      linker, so that the previously S-nitrosylated cysteine residues are finally
      biotinylated. Afterwards, the biotinylated proteins can be detected with anti
      biotin antibodies or can be purified by affinity chromatography on neutravidin
      agarose. In this chapter, we give a detailed description of the biotin switch
      method, which can be used for proteomics approach to identify candidates for
      protein S-nitrosylation as well as to analyse S-nitrosylation of selected
      proteins.

PMID- 19157020
TI  - [Construction of a system for exercise leader training ("Setagaya Genki Taisou
      Leader") and activity support for community-dwelling elderly].

PMID- 19157021
TI  - [Determinants of change in the revenue to cost ratio of municipal hospitals by
      scale in Japan].

PMID- 19157022
TI  - [Influence of malalignment and malocclusion on mental and physical health
      consciousness in senior high school students].
AB  - OBJECTIVES: Dental examinations and a questionnaire survey were carried out
      simultaneously in senior high schools to investigate influence of tooth
      misalignment and malocclusion on mental and physical health-consciousness of the
      students. METHODS: The questionnaire survey concerning health-consciousness was
      collected after the dental examination. The students were divided into three
      groups by their findings: "within a normal range"; "mild-", and "severe-
      misalignment and malocclusion". The relationship between the severity of dental
      abnormality and mental and physical status in health by the questionnaire survey
      was studied. RESULTS: The severity of misalignment and malocclusion correlated
      with (1) degree of consciousness of irregular teeth, and (2) degree of negative
      evaluation of themselves for their health-consciousness. CONCLUSION: There is
      possibility that the severity of misalignment and malocclusion corresponds to a
      negative self evaluation and causes mental stress. It is suggested that it is
      very important to identify young people with such problems at an early stage, and
      then to consult and promote correct dental alignment and occlusion, providing not
      only sufficient mastication but also unhampered mental development.

PMID- 19157023
TI  - [Desire for slenderness in adolescent women: transition during 14 years in
      dietetic students of a junior college].

PMID- 19157024
TI  - [Significance of epidemiological glaucoma survey --awareness of normal-tension
      glaucoma].

PMID- 19157026
TI  - [Measurement of spontaneous blinks with a high-speed blink analyzing system].
AB  - PURPOSE: In order to analyze spontaneous blink kinematics easily and
      circumstantially, we developed a new method using an intelligent vision system
      (IVS) camera with a 1 KHz sampling rate, and evaluated the efficacy of this
      system. METHOD: Eleven healthy male volunteers were examined after obtaining
      informed consent. Eyelid movements in the primary eye position were recorded with
      an IVS camera twice, for 30 seconds each. Data of upper lid position and lid
      movement were plotted every 1 msec by image processing of the recorded images.
      Thereafter blink duration and maximum blink velocity in every spontaneous blink
      were calculated. RESULTS: Thirty-nine instances of complete lid-closure type and
      seventy of incomplete lid-closure type of spontaneous blinks were observed. The
      average duration of the down-phase, the up-phase, and the total blink were the
      same for both types; about 100 msec., 220 msec., and 320 msec. respectively. The
      average down-phase maximum velocity was about 180 mm/sec. in complete lid
      closures and 120 mm/sec. in incomplete lid-closures. The average up-phase maximum
      velocity was about 60 mm/sec. in complete lid-closures and 45 mm/sec. in
      incomplete lid-closures. Blink amplitude and the maximum velocity achieved during
      lid closing and opening were strongly correlated and exhibited a linear
      relationship (r = 0.85, r = 0.73 p < 0.0001). CONCLUSION: This new, non-invasive
      system is an easy to use measuring method for blink kinematics and is highly
      reliable and very useful.

PMID- 19157025
TI  - [Tajimi Study review].
AB  - The results of The Tajimi Study (a population-based prevalence survey of glaucoma
      in Tajimi City performed by the Japan Glaucoma Society) are summarized. The
      Tajimi Study was carried out from September, 2000 to October, 2001 to investigate
      the prevalence of glaucoma among residents aged 40 years old or over in Tajimi.
      Seventy-eight point one % of 3,870 eligible people from 4,000 subjects who had
      been randomly selected from the 54,165 over 40 years old residents in Tajimi
      participated in the study. Estimated prevalence of all glaucoma and
      glaucoma/suspected glaucoma were 5.0 (95% confidence interval [CI], 4.2-5.8)% and
      7.5 (95% CI, 6.5-8.4)%. The prevalence of primary open angle glaucoma (POAG),
      primary angle closure glaucoma (PACG), and secondary glaucoma (SG) were 3.9 (95%
      CI, 3.2-4.6)%, 0.6 (95% CI, 0.4-0.9)%, and 0.5 (95% CI, 0.2-0.7)%, respectively.
      Including suspected cases, the prevalence of POAG, PACG, and SG was 6.0 (5.1
      6.8)%, 0.8 (0.5-1.2)%, 0.7 (0.4-1.0)%. High intraocular pressure, myopia, and
      older age were shown to be statistically significant risk factors for POAG. It
      was suggested that the Frequency Doubling Technology is a good candidate as a
      screening test for glaucoma. The leading cause of low vision was cataracts.
      Investigation of refractive status showed that the prevalence of myopia(spherical
      equivalence [SE] < 0.5 diopters) and high myopia (SE < -5.0 diopters) was 41.8
      (40.0-43.6)% and 8.2 (7.2-9.2)%, respectively.

PMID- 19157027
TI  - [Two-year results following photodynamic therapy for age-related macular
      degeneration].
AB  - PURPOSE: To investigate the visual outcome 2 years after photodynamic therapy
      (PDT) in patients with exudative age-related macular degeneration (AMD) and
      polypoidal choroidal vasculopathy (PCV). METHODS: Thirty-six eyes undergoing PDT
      were retrospectively studied. Seventeen eyes of AMD (AMD group) and nineteen eyes
      of PCV (PCV group) were evaluated. RESULTS: In the AMD group, the mean pre-PDT
      visual acuity was 0.19. The mean post-PDT visual acuity was 0.16 two years after
      the PDT. Two years after PDT, the Log MAR visual acuity improved by 0.2 or more
      in 3 eyes (17.7%), but it decreased by 0.2 or more in 4 eyes (23.5%). In the PCV
      group, the mean pre-PDT visual acuity was 0.34. The mean post-PDT visual acuity
      was 0.20 two years after PDT. The Log MAR visual acuity improved by 0.2 or more
      in 5 eyes (26.3%), but it decreased by 0.2 or more in 7 eyes (36.8%).
      CONCLUSIONS: In this series of patients, more than half of the two groups were
      able to maintain their visual acuity for 2 years after PDT. Although the average
      visual acuity of the AMD group was worse than that of the PCV group, the AMD
      group was able to maintain their visual acuity for 2 years after PDT. The average
      visual acuity of the PCV group decreased 2 years after PDT.

PMID- 19157028
TI  - [Classification and diagnostic criteria of age-related macular degeneration].
AB  - New classification and diagnosis criteria of age-related macular degeneration in
      Japan are described. The prodromal stage is classified into 1) soft drusen and 2)
      retinal pigment epithelial abnormalities. Age-related macular degeneration is
      classified into 1) exudative age-related macular degeneration and 2) atrophic
      macular degeneration. As specific types of exudative age-related macular
      degeneration, (1) polypoidal choroidal vasculopathy and (2) retinal angiomatous
      proliferation are also included. Diagnostic criteria include 1) prodromal stage,
      2) exudative age-related macular degeneration, 3) atrophic age-related macular
      degeneration, and 4) exclusion criteria. The diagnosis of exudative age-related
      macular degeneration is certain when one of the following conditions in present:
      (1) choroidal neovascularization, (2) serous retinal pigment epithelial
      detachment, (3) hemorrhagic retinal pigment epithelial detachment, or (4)
      fibrotic scar in the macula.

PMID- 19157029
TI  - [Case of inferonasal subconjunctival orbital fat herniation].
AB  - BACKGROUND: We report a case with orbital fat herniation beneath the inferonasal
      conjunctiva, which is very rare in the literature. CASE: A 52-year-old non-obese
      female. The subconjunctival mass in the right eye that had formed spontaneously
      at a young age was yellow, soft, and easily retreated into the orbit with
      pressure. A magnetic resonance image showed that the intraconal orbital fat
      herniated through a space that was formed by the inferonasal sclera and the
      intermuscular septum between the medial rectus muscle and the inferior rectus
      muscle. Surgical resection obtained good results. CONCLUSION: This route of fat
      herniation in this case is similar to that of superotemporal lesions in previous
      reports. One possible explanation of the mechanism of such a rare lesion is
      congenital weakness in the inferonasal Tenon's capsule.

PMID- 19157030
TI  - Health services marketing.

PMID- 19157031
TI  - The four Cs of marketing success.

PMID- 19157032
TI  - Marketers must advocate for patients.

PMID- 19157033
TI  - Right message at the right time. Digital signage delivers information hospitals
      and patients want.

PMID- 19157034
TI  - Constructing a better brand. High-performance brands begin with a solid
      foundation.

PMID- 19157035
TI  - Advertising gone too far?

PMID- 19157036
TI  - More is not necessarily better.

PMID- 19157037
TI  - In search of the unhappy customer. Pay attention to what's not working on your
      Web site.

PMID- 19157038
TI  - Coffee, tea or better living? Cafe culture provides support for seniors.

PMID- 19157039
TI  - De-marketing for healthcare organizations.

PMID- 19157040
TI  - Individual and contextual predictors of inhalant use among 8th graders: a
      multilevel analysis.
AB  - Few studies of inhalant use have examined a large number of predictors at the
      individual level, including risk and protective factors and delinquent behavior,
      while also taking into account contextual variables (such as school size and
      poverty rates). This exploratory study uses 8th grade data from a large-scale
      survey of students in Kentucky to examine individual and contextual predictors of
      prevalence of inhalant use, and compares the predictors of inhalant use with
      factors predicting the use of marijuana and other drug use. Hierarchical
      Generalized Linear Modeling results using a logit link function suggest that the
      relationships between inhalant use and some of these factors are different than
      the relationships between the factors and both marijuana and other drug use.
      Implications for prevention of inhalant use are discussed.

PMID- 19157041
TI  - Protective behavioral strategies and negative alcohol-related consequences in
      college students.
AB  - OBJECTIVE: Alcohol abuse among college students is associated with a quality of
      life burden. The current study replicated and extended previous research on
      protective behavioral strategies (PBS) by examining relationships between PBS use
      and negative alcohol-related consequences. METHOD: A national sample of 29,792
      U.S. college students who completed the National College Health Assessment during
      spring 2004 was included. Using a retrospective analysis of cross-sectional data,
      relationships between PBS use and negative alcohol-related consequences were
      examined. RESULTS: Greater PBS use was associated with fewer negative alcohol
      related consequences, while less frequent use of PBS was correlated with
      increased negative alcohol-related consequences. DISCUSSION: The current study
      findings strongly support expanded educational alcohol-intervention programs
      promoting greater PBS use aimed at reducing or completely alleviating negative
      alcohol-related consequences (e.g., BASICS, ASTP). Future research should further
      investigate such PBS-based intervention programs, examine the existence of latent
      PBS, and study use of combined PBS.

PMID- 19157042
TI  - Immediate and short-term effects of the 5th grade version of the keepin' it REAL
      substance use prevention intervention.
AB  - This study assessed the immediate and short-term outcomes of adapting a
      culturally-grounded middle school program, keepin' it REAL, for elementary school
      students. After curriculum adaptation, 10 schools were randomly assigned to the
      intervention in 5th grade with follow-up boosters in 6th grade; 13 schools were
      randomly assigned to the control condition, implementing the school's pre
      existing substance use prevention programming. Students (n=1566) completed a
      questionnaire prior to curriculum implementation and follow-up questionnaires
      toward the end of 5th and 6th grade. The 5th grade kiR curriculum generally
      appeared no more effective than the control schools' programming in changing
      students' resistance or decision-making skills; substance use intentions,
      expectancies, or normative beliefs; or lifetime and recent substance use. Such
      findings have implications for the age appropriateness of school-based programs.

PMID- 19157043
TI  - Role of family resources and paternal history of substance use problems in
      psychosocial adjustment among school-aged children.
AB  - The present study examines the role of family resources (parenting style and
      family cohesion) and paternal history of substance abuse on the psychosocial
      adjustment of their school-aged children. Data were collected from 148 children
      aged 8-11 (72 of fathers with history of substance use disorder, 76 children of
      fathers with no substance use problems) and their mothers. Results draw attention
      to the differences between the subjective experiences of the child and those of
      the mother, and by indicating that the effect of the interaction between the
      father's and the mother's control parenting style on the child's psychosocial
      outcome is greater than the sum total of influences of each of them separately.

PMID- 19157044
TI  - Differences in drinking behavior and access to alcohol between Native American
      and white adolescents.
AB  - We investigated differences in drinking behaviors and sources of alcohol among
      Native American (n=361) and White adolescents (n=1735), ages 11 to 19. Native
      American youth were more likely to have consumed alcohol in their lifetime and
      been intoxicated in the last 30 days than Whites. Native American drinkers were
      almost twice as likely to have gotten alcohol from an adult and twice as likely
      to have obtained alcohol from someone under 21. White drinkers were four times as
      likely to have obtained alcohol from their parents. Youth did not differ in
      access to alcohol from other social sources. Because youth access alcohol from
      different social sources, strategies to limit access must consider these
      differences. This study underscores the importance of examining ethnic-specific
      alcohol access patterns.

PMID- 19157045
TI  - The use of fry (embalming fluid and PCP-laced cigarettes or marijuana sticks)
      among crack cocaine smokers.
AB  - Statistics show that the prevalence of crack cocaine use and embalming fluid and
      phencyclidine (PCP)-laced cigarettes or marijuana sticks, commonly referred to on
      the street as "fry" or "wet" is a problem; however, the relationship between
      these substances of abuse and concurrent polydrug use is unknown. In the present
      study, a cross-sectional survey was conducted among 426 African-American crack
      users in Houston, Texas, to investigate the difference between those who
      concurrently reported lifetime (defined as at least one usage of fry in life) fry
      use and those who stated they never used fry. The data were analyzed using chi
      square and logistic regression analyses. Fry users were significantly more likely
      than non-users to not have a casual sex partner (92% users vs. 84% non-users, p <
      or = 0.05) and were more likely to have been diagnosed with gonorrhea in the past
      12 months (9% users vs. 2% non-users, p < or = 0.05). In addition fry users had
      significantly higher odds of currently trading sex for drugs (OR = 2.30, p < or =
      0.05), marijuana use (OR = 12.11, p < or = 0.05), and codeine (syrup) use (OR =
      8.10, p < or = 0.05). These findings are important in determining the "cultural
      novelties" relative to crack and fry use among younger African Americans.

PMID- 19157046
TI  - Salvia divinorum use among a college student sample.
AB  - The recreational use of Salvia divinorum has received increased attention by
      media outlets and policy-makers in recent years. The vast absence of research to
      guide the dissemination of information has prompted this research note describing
      the use of this substance in a large public institution of higher education. The
      prevalence of Salvia divinorum is described in this context and a description of
      patterns of use, methods of acquisition, and a subjective estimation of
      continuance are proffered.

PMID- 19157047
TI  - Entry-level interprofessional education: perceptions of physical and occupational
      therapists currently practicing in Ontario.
AB  - To gain insight into the specific interprofessional education (IPE) needs of
      occupational and physical therapists, an online questionnaire was developed and
      distributed to currently practicing therapists in the province of Ontario,
      Canada. The questionnaire included both open- and closed-ended questions to
      survey the opinions, perceptions, and experiences of therapists working both in
      public and private practice who possess varying levels of clinical training and
      years of experience. Data collection resulted in 765 responses (397 OTs, 368
      PTs), which allowed for a 95% confidence level based on 2007 population totals
      supplied by the professional colleges. Data analysis involved descriptive data
      analysis in conjunction with percentage comparisons of the responses as well as
      the coding of responses to open-ended questions. The therapists' opinions
      regarding the type, amount, and need for IPE were compared based on discipline
      and area of practice. Overall, the data show that 97% of OTs and PTs in both
      public and private settings hold IPE to be important for effective clinical
      practice. When asked about their own IPE experiences, only 50% of OTs and 43% of
      PTs felt that they received an appropriate level of IPE training during their
      entry-level clinical training. When given the choice to select the location/time
      when IPE should be completed, 65% choose clinical placements, with 26% classroom.
      Implications of the findings as well as study limitations are discussed.

PMID- 19157048
TI  - Use of personal digital assistants among dietitians and dietetic students in
      Oklahoma: should programs incorporate PDA training into their curricula?
AB  - The objective of this study was to assess the use of personal digital assistants
      (PDAs) among dietitians and dietetic students in Oklahoma and the desire for
      training in the use of PDAs. A survey was mailed to 648 dietitians and dietetic
      students to assess their PDA use and interest in PDA training. Frequency and
      percentage of responses were determined. A total of 320 usable surveys were
      returned, for a response rate of 49%. Sixteen percent of responders were dietetic
      students. The responses of students did not differ from those of dietitians, so
      all responses were combined. Subjects were primarily female, between 21 and 50
      yrs of age, and had practiced for 5 yrs or more, similar to the demographics of
      dietitians nationally. Twenty-four percent of responders currently use a PDA,
      primarily as an organizational tool. Twenty-eight percent of the users indicated
      that they had received training in PDA use. Thirty-seven percent of the users
      were using a PDA for nutrition assessments, and 28% were using it for nutrition
      support. Of nonusers, 80% indicated that they would use a PDA if training were
      available. PDAs were used most often as an organizational tool, seldom for
      nutrition-specific applications. Dietitians and students expressed an interest in
      receiving training in PDA use, preferably from state and local dietetic
      associations. PDA training might also be incorporated into academic dietetic
      programs, and employers could provide training in the workplace.

PMID- 19157049
TI  - Leadership content important in athletic training education with implications for
      allied health care.
AB  - A two-phase exploratory and comparative research study using a Delphi technique
      and a web-based national survey was done to determine leadership content (i.e.,
      theories, styles, or practices) important to include in athletic training
      education. Eighteen athletic training experts participated in the Delphi
      technique, followed by 161 athletic trainers completing the national survey.
      Consensus of experts was reached after two rounds (77% interrater agreement,
      alpha = 0.80 and alpha = 0.93 per respective round) and identified 31 leadership
      content items important to include in athletic training education. The national
      sample then rated importance of each leadership content area for inclusion in
      four types of athletic training education programs (entry-level baccalaureate,
      entry-level master's degree, postgraduate certifications, and doctoral degree).
      The respondents ranked the leadership content in order of importance according to
      mean (mean = 1.53 +/- 0.84 to 2.55 +/- 0.55; scale, 0-3). Twenty-two content
      items (63%) were rated at least "very important" (mean > or = 2.0). Exploratory
      factor analysis established construct validity and organized leadership content
      by three factors: managerial leadership and knowledge management; leadership
      theories; and leadership issues, trends, and policies (alpha = 0.84-0.91).
      Repeated-measures analysis of variance (Sidak post-hoc adjustments) established
      criterion-related concurrent validity, which found increasing levels of
      importance as education type progressed (F = 4.88, p = 0.003-32.56, p = 0.000).
      Adding leadership content within athletic training enhances the
      professionalization of students, facilitates leadership competency among students
      and practicing professionals enrolled in postcertification educational programs,
      and facilitates job placement and role.

PMID- 19157050
TI  - Final-year diagnostic radiography students' perception of role models within the
      profession.
AB  - Within a clinical education setting, the value of role models and prescribed
      mentors can be seen as an important influence in shaping the student's future as
      a diagnostic radiographer. A study was undertaken to create a new understanding
      of how diagnostic radiography students perceive role models and professional
      behavior in the workforce. The study aimed to determine the impact of clinical
      education in determining modeling expectations, role model identification and
      attributes, and the integration of academic education and "hands-on" clinical
      practice in preparing diagnostic radiography students to enter the workplace.
      Thirteen final-year (third-year) diagnostic radiography students completed an
      hour-long interview regarding their experiences and perceptions of role models
      while on clinical placement. The key concepts that emerged illustrated that
      students gravitate toward radiographers who enjoy sharing practical experiences
      with students and are good communicators. Unique to diagnostic radiography,
      students made distinctions about the presence of role models in private versus
      public service delivery. This study gives insight to clinical educators in
      diagnostic radiography and wider allied health into how students perceive role
      models, interact with preceptors, and combine real-life experiences with formal
      learning.

PMID- 19157051
TI  - Perceptions of scientific misconduct among graduate allied health students
      relative to ethics education and gender.
AB  - A study was conducted to determine the influence of ethics education and gender
      on students' perceptions of scientific misconduct. Subjects were graduate
      students from five allied health professions programs at a single university, who
      were asked to complete an online survey consisting of 48 questions (dichotomous
      and Likert-scale questions): 36 questions assessed the perceptions of students
      regarding the concerns of scientific misconduct (dependent variable), 10 were
      demographic questions, and 2 were free-text questions soliciting clarification of
      any responses. Out of 202 graduate students, 72 students (54 female, 17 male)
      completed the survey. Forty (56%) of the participants had taken at least one
      ethics course, while 31 (44%) had not taken any ethics courses. Analysis of
      Scientific Integrity Scores calculated from survey responses of health
      professions students revealed that students who had taken an ethics course scored
      significantly higher on the scale of the use of humans in research than students
      who had not taken an ethics course. Students who had taken medical ethics courses
      scored significantly higher on the scale regarding genetics research than
      students who had taken other ethics courses. Women scored significantly higher
      than men on the scale regarding the use of animals in research.

PMID- 19157052
TI  - Faculty perceptions of occupational therapy program directors' leadership styles
      and outcomes of leadership.
AB  - This research study investigated the relationship between faculty perceptions of
      occupational therapy program directors' leadership styles and outcomes of
      leadership and the effects of moderating demographic and institutional
      characteristics. Data for this study were collected utilizing the Multifactor
      Leadership Questionnaire Form 5X and the self-designed Demographic and
      Institution Questionnaire. The study working sample included 184 graduate
      occupational therapy faculty members from 98 (65%) of all accredited academic
      occupational therapy programs in the United States for the 2005-06 academic year.
      Major findings from the study indicate that, in general, transformational
      leadership had a significant (p < 0.001) positive predictive relationship with
      the leadership outcomes whereas transactional leadership had a significant (p <
      0.001) negative predictive relationship. The contingent reward leadership
      attribute (although belonging to the transactional leadership construct) was
      found to be a positive predictor of leadership outcomes. Demographic and
      institutional characteristics did not have a significant (p > 0.01) influence on
      perceived leadership styles and leadership outcomes. The results of this research
      show that the most effective occupational therapy leaders in academia have been
      found to be those who adopt and utilize a full range of leadership styles that
      combine both transformational and transactional contingent reward leadership
      styles and suggest common effectiveness for other allied health fields.

PMID- 19157053
TI  - Allied health disaster volunteering.
AB  - Allied health practitioners will play an important role in providing medical care
      following a disaster. The clinical and laboratory skills possessed by allied
      health practitioners will be of extreme importance in the processing of disaster
      victims. The degree that allied health practitioners can help process disaster
      victims will play a large role in helping stabilize survivors of man-made or
      natural disasters. Those allied health practitioners skilled in triage, patient
      assessment, and emergency treatment of those injured can make a large difference
      in improving the utilization of human resources at an emergency site and thereby
      potentially improve treatment outcomes. Failure of a health professional to
      preregister as a health volunteer can affect the quality and responsiveness of a
      community's surge capacity. The rationale for advance registration ensures that
      the time-intensive effort of identifying professional credentials and licenses
      does not consume or divert resources that are necessary for mitigation of the
      immediate emergency. Of equal importance for allied health practitioners are the
      liability issues that exist in providing health care services outside of a formal
      employment agreement.

PMID- 19157054
TI  - Preventing practice errors and improving patient safety: an examination of case
      studies reflecting common errors in occupational therapy practice.
AB  - Like other health care professionals, occupational therapists make errors in
      clinical practice. Only recently have we systematically studied errors in
      occupational therapy practice. In this report, key findings from two grant
      projects in occupational therapy practice errors are further examined.
      Specifically, this report includes an in-depth analysis of five examples of
      occupational therapy practice errors in physical rehabilitation and geriatric
      settings. These examples from the five most commonly reported causes of errors
      found in a national survey study on occupational therapy errors are misjudgment,
      lack of preparation, lack of experience, lack of knowledge, and insufficient
      communication. For each of the five examples, hypothesized causes of errors and
      their implications for professional education training and current occupational
      therapy practice are explored. It is hoped that this report helps to better
      inform practice and educational approaches to contribute to the prevention and
      reduction of occupational therapy and other health care practice errors.

PMID- 19157055
TI  - Molecular, clinical and environmental toxicology. Preface.

PMID- 19157056
TI  - Historical milestones and discoveries that shaped the toxicology sciences.
AB  - Knowledge of the toxic and healing properties of plants, animals, and minerals
      has shaped civilization for millennia. The foundations of modern toxicology are
      built upon the significant milestones and discoveries of serendipity and crude
      experimentation. Throughout the ages, toxicological science has provided
      information that has shaped and guided society. This chapter examines the
      development of the discipline of toxicology and its influence on civilization by
      highlighting significant milestones and discoveries related to toxicology. The
      examples shed light on the beginnings of toxicology, as well as examine lessons
      learned and re-learned. This chapter also examines how toxicology and the
      toxicologist have interacted with other scientific and cultural disciplines,
      including religion, politics, and the government. Toxicology has evolved to a
      true scientific discipline with its own dedicated scientists, educational
      institutes, sub-disciplines, professional societies, and journals. It now stands
      as its own entity while traversing such fields as chemistry, physiology,
      pharmacology, and molecular biology. We invite you to join us on a path of
      discovery and to offer our suggestions as to what are the most significant
      milestones and discoveries in toxicology. Additional information is available on
      the history section of Toxipedia (www.toxipedia.org).

PMID- 19157057
TI  - Physiologically based toxicokinetic models and their application in human
      exposure and internal dose assessment.
AB  - Human populations may exhibit large interindividual variation in toxicokinetic
      response to chemical exposures. Rapid developments in dosimetry research have
      brought medicine and public health closer to understanding the biological basis
      of this heterogeneity. The toxicokinetic behavior of chemicals is, in part,
      controlled by the properties of the epithelium surrounding organs, some of which
      are effective barriers to penetration into the systemic circulation.
      Physiologically based toxicokinetic (PBTK) models have been developed and used to
      simulate the mechanism of uptake into the systemic circulation, to extrapolate
      between doses and exposure routes, and to estimate internal dosimetry and sources
      of heterogeneity in animals and humans. Recent improvements to PBTK models
      include descriptions of active transport across biological membranes, carrier
      mediated clearance, and fractal kinetics. The expanding area of toxicogenetics
      has provided valuable insight for delineating toxicokinetic differences between
      individuals; genetic differences include inherited single nucleotide
      polymorphisms, copy number variants, and dynamic changes in the methylation
      pattern of imprinted genes. This chapter discusses the structure of PBTK models
      and how toxicogenetic information and newer biological descriptions have improved
      our understanding of variability in response to toxicant exposures.

PMID- 19157059
TI  - Genotoxicity: damage to DNA and its consequences.
AB  - A genotoxin is a chemical or agent that can cause DNA or chromosomal damage. Such
      damage in a germ cell has the potential to cause a heritable altered trait
      (germline mutation). DNA damage in a somatic cell may result in a somatic
      mutation, which may lead to malignant transformation (cancer). Many in vitro and
      in vivo tests for genotoxicity have been developed that, with a range of
      endpoints, detect DNA damage or its biological consequences in prokaryotic (e.g.
      bacterial) or eukaryotic (e.g. mammalian, avian or yeast) cells. These assays are
      used to evaluate the safety of environmental chemicals and consumer products and
      to explore the mechanism of action of known or suspected carcinogens. Many
      chemical carcinogens/mutagens undergo metabolic activation to reactive species
      that bind covalently to DNA, and the DNA adducts thus formed can be detected in
      cells and in human tissues by a variety of sensitive techniques. The detection
      and characterisation of DNA adducts in human tissues provides clues to the
      aetiology of human cancer. Characterisation of gene mutations in human tumours,
      in common with the known mutagenic profiles of genotoxins in experimental
      systems, may provide further insight into the role of environmental mutagens in
      human cancer.

PMID- 19157060
TI  - Role of DNA repair in the protection against genotoxic stress.
AB  - The genome of all organisms is constantly attacked by a variety of environmental
      and endogenous mutagens that cause cell death, apoptosis, senescence, genetic
      diseases and cancer. To mitigate these deleterious endpoints of genotoxic
      reactions, living organisms have evolved one or more mechanisms for repairing
      every type of naturally occurring DNA lesion. For example, double-strand breaks
      are rapidly religated by non-homologous end-joining. Homologous recombination is
      used for the high-fidelity repair of interstrand cross-links, double-strand
      breaks and other DNA injuries that disrupt the replication fork. Some genotoxic
      lesions inflicted by alkylating agents can be repaired by direct reversal of DNA
      damage. The base excision repair pathway takes advantage of multiple DNA
      glycosylases to remove modified or incorrect bases. Finally, the nucleotide
      excision repair machinery provides a versatile strategy to monitor DNA quality
      and eliminate all forms of helix-distorting DNA lesions, including a wide
      diversity of carcinogen adducts. The efficiency of DNA repair responses is
      enhanced by their coupling to transcription and coordination with the cell cycle
      circuit.

PMID- 19157058
TI  - The role of biotransformation and bioactivation in toxicity.
AB  - Biotransformation is essential to convert lipophilic chemicals to water-soluble
      and readily excretable metabolites. Formally, biotransformation reactions are
      classified into phase I and phase II reactions. Phase I reactions represent the
      introduction of functional groups, whereas phase II reactions are conjugations of
      such functional groups with endogenous, polar products. Biotransformation also
      plays an essential role in the toxicity of many chemicals due to the metabolic
      formation of toxic metabolites. These may be classified as stable but toxic
      products, reactive electrophiles, radicals, and reactive oxygen metabolites. The
      interaction of toxic products formed by biotransformation reactions with cellular
      macromolecules initiates the sequences resulting in cellular damage, cell death
      and toxicity.

PMID- 19157061
TI  - On the impact of the molecule structure in chemical carcinogenesis.
AB  - Cancer is as a highly complex and multifactorial disease responsible for the
      death of hundreds of thousands of people in the western countries every year.
      Since cancer is clonal and due to changes at the level of the genetic material,
      viruses, chemical mutagens and other exogenous factors such as short-waved
      electromagnetic radiation that alter the structure of DNA are among the principal
      causes. The focus of this present review lies on the influence of the molecular
      structure of two well-investigated chemical carcinogens from the group of
      polycyclic aromatic hydrocarbons (PAHs), benzo[a]pyrene (BP) and
      dibenzo[a,l]pyrene (DBP). Although there is only one additional benzo ring
      present in the latter compound, DBP exerts much stronger genotoxic and
      carcinogenic effects in certain tumor models as compared to BP. Actually, DBP has
      been identified as the most potent tumorigen among all carcinogenic PAHs tested
      to date. The genotoxic effects of both compounds investigated in mammalian cells
      in culture or in animal models are described. Comparison of enzymatic activation,
      DNA binding levels of reactive diol-epoxide metabolites, efficiency of DNA adduct
      repair and mutagenicity provides some clues on why this compound is about 100
      fold more potent in inducing tumors than BP. The data published during the past
      20 years support and strengthen the idea that compound-inherent physicochemical
      parameters, along with inefficient repair of certain kinds of DNA lesions formed
      upon metabolic activation, can be considered as strong determinants for high
      carcinogenic potency of a chemical.

PMID- 19157062
TI  - Chemical induced alterations in p53 signaling.
AB  - The p53 protein is one of the most important tumor suppressors. The present
      review summarizes aspects of p53 function and its role in cancer development.
      Some of the most well-characterized molecular mechanisms affecting p53
      regulation, stabilization, inactivation and downstream events are described. A
      major focus is on how xenobiotics can interfere with p53 function and on its role
      in chemical carcinogenesis. In the final section of this chapter we discuss
      future aspects on how knowledge about p53 can be used in testing of carcinogens
      and in risk assessment.

PMID- 19157063
TI  - Molecular pathways involved in cell death after chemically induced DNA damage.
AB  - DNA damage is at the center of the genesis, progression and treatment of cancer.
      We review here the molecular mechanisms of the DNA damage inducing small
      molecules most commonly used in cancer therapy. Cell cycle control and DNA repair
      mechanisms are known to be activated after DNA damage. Here, we revise recent
      discoveries related to the cell cycle control and DNA repair processes and how
      these findings are being utilized for the more efficient, powerful and selective
      therapies for cancer treatment.

PMID- 19157064
TI  - The aryl hydrocarbon receptor at the crossroads of multiple signaling pathways.
AB  - The aryl hydrocarbon receptor (AHR) has long been recognized as a ligand
      activated transcription factor responsible for the induction of drug-metabolizing
      enzymes. Its role in the combinatorial matrix of cell functions was established
      long before the first report of an AHR cDNA sequence was published. It is only
      recently that other functions of this protein have begun to be recognized, and it
      is now clear that the AHR also functions in pathways outside of its well
      characterized role in xenobiotic enzyme induction. Perturbation of these pathways
      by xenobiotic ligands may ultimately explain much of the toxicity of these
      compounds. This chapter focuses on the interactions of the AHR in pathways
      critical to cell cycle regulation, mitogen-activated protein kinase cascades,
      differentiation and apoptosis. Ultimately, the effect of a particular AHR ligand
      on the biology of the organism will depend on the milieu of critical pathways and
      proteins expressed in specific cells and tissues with which the AHR itself
      interacts.

PMID- 19157065
TI  - Mapping the epigenome--impact for toxicology.
AB  - Recent advances in technological approaches for mapping and characterizing the
      epigenome are generating a wealth of new opportunities for exploring the
      relationship between epigenetic modifications, human disease and the therapeutic
      potential of pharmaceutical drugs. While the best examples for xenobiotic-induced
      epigenetic perturbations come from the field of non-genotoxic carcinogenesis,
      there is growing evidence for the relevance of epigenetic mechanisms associated
      with a wide range of disease areas and drug targets. The application of
      epigenomic profiling technologies to drug safety sciences has great potential for
      providing novel insights into the molecular basis of long-lasting cellular
      perturbations including increased susceptibility to disease and/or toxicity,
      memory of prior immune stimulation and/or drug exposure, and transgenerational
      effects.

PMID- 19157066
TI  - Receptors mediating toxicity and their involvement in endocrine disruption.
AB  - Many toxic compounds exert their harmful effects by activating of certain
      receptors, which in turn leads to dysregulation of transcription. Some of these
      receptors are so called xenosensors. They are activated by external chemicals and
      evoke a cascade of events that lead to the elimination of the chemical from the
      system. Other receptors that are modulated by toxic substances are hormone
      receptors, particularly the ones of the nuclear receptor family. Some
      environmental chemicals resemble endogenous hormones and can falsely activate
      these receptors, leading to undesired activity in the cell. Furthermore,
      excessive activation of the xenosensors can lead to disturbances of the integrity
      of the system as well. In this chapter, the concepts of receptor-mediated
      toxicity and hormone disruption are introduced. We start by describing
      environmental chemicals that can bind to xenosensors and nuclear hormone
      receptors. We then describe the receptors most commonly targeted by environmental
      chemicals. Finally, the mechanisms by which receptor-mediated events can disrupt
      the system are depicted.

PMID- 19157067
TI  - Toxicogenomics: transcription profiling for toxicology assessment.
AB  - Toxicogenomics, the application of transcription profiling to toxicology, has
      been widely used for elucidating the molecular and cellular actions of chemicals
      and other environmental stressors on biological systems, predicting toxicity
      before any functional damages, and classification of known or new toxicants based
      on signatures of gene expression. The success of a toxicogenomics study depends
      upon close collaboration among experts in different fields, including a
      toxicologist or biologist, a bioinformatician, statistician, physician and,
      sometimes, mathematician. This review is focused on toxicogenomics studies,
      including transcription profiling technology, experimental design, significant
      gene extraction, toxicological results interpretation, potential pathway
      identification, database input and the applications of toxicogenomics in various
      fields of toxicological study.

PMID- 19157069
TI  - High-throughput screening for analysis of in vitro toxicity.
AB  - The influence of combinatorial chemistry and high-throughput screening (HTS)
      technologies in the pharmaceutical industry during the last 10 years has been
      enormous. However, the attrition rate of drugs in the clinic due to toxicity
      during this period still remained 40-50%. The need for reduced toxicity failure
      led to the development of early toxicity screening assays. This chapter describes
      the state of the art for assays in the area of genotoxicity, cytotoxicity,
      carcinogenicity, induction of specific enzymes from phase I and II metabolism,
      competition assays for enzymes of phase I and II metabolism, embryotoxicity as
      well as endocrine disruption and reprotoxicity. With respect to genotoxicity, the
      full Ames, Ames II, Vitotox, GreenScreen GC, RadarScreen, and non-genotoxic
      carcinogenicity assays are discussed. For cytotoxicity, cellular proliferation,
      calcein uptake, oxygen consumption, mitochondrial activity, radical formation,
      glutathione depletion as well as apoptosis are described. For high-content
      screening (HCS), the possibilities for analysis of cytotoxicity, micronuclei,
      centrosome formation and phospholipidosis are examined. For embryotoxicity,
      endocrine disruption and reprotoxicity alternative assays are reviewed for fast
      track analysis by means of nuclear receptors and membrane receptors. Moreover,
      solutions for analyzing enzyme induction by activation of nuclear receptors, like
      AhR, CAR, PXR, PPAR, FXR, LXR, TR and RAR are given.

PMID- 19157068
TI  - The role of toxicoproteomics in assessing organ specific toxicity.
AB  - Aims of this chapter on the role of toxicoproteomics in assessing organ-specific
      toxicity are to define the field of toxicoproteomics, describe its development
      among global technologies, and show potential uses in experimental toxicological
      research, preclinical testing and mechanistic biological research. Disciplines
      within proteomics deployed in preclinical research are described as Tier I
      analysis, involving global protein mapping and protein profiling for differential
      expression, and Tier II proteomic analysis, including global methods for
      description of function, structure, interactions and post-translational
      modification of proteins. Proteomic platforms used in toxicoproteomics research
      are briefly reviewed. Preclinical toxicoproteomic studies with model liver and
      kidney toxicants are critically assessed for their contributions toward
      understanding pathophysiology and in biomarker discovery. Toxicoproteomics
      research conducted in other organs and tissues are briefly discussed as well. The
      final section suggests several key developments involving new approaches and
      research focus areas for the field of toxicoproteomics as a new tool for
      toxicological pathology.

PMID- 19157070
TI  - Facilitators and outcomes of student engagement in a college setting.
AB  - The authors examined intensely engaging (i.e., flow) experiences in the context
      of college coursework to gain a better understanding of their antecedents and
      outcomes. College students (N=137) completed a Web-based survey that assessed (a)
      flow experiences; (b) academic work characteristics including role clarity,
      professor support for autonomy, and feedback; and (c) psychological and physical
      health. The authors found that flow completely mediated the relation between
      academic work characteristics and psychological well-being. They also found that
      flow had an indirect effect through psychological well-being on physical health.
      These findings suggest restructuring academic work to be clear and autonomous and
      giving ample feedback opportunities to facilitate intense student engagement and
      mental and physical wellness.

PMID- 19157071
TI  - How task characteristics and social support relate to managerial learning:
      empirical evidence from Dutch home care.
AB  - Researchers have revealed that managers profit most from informal and on-the-job
      learning. Moreover, research has shown that task characteristics and social
      support affect informal learning. On the basis of these insights, the authors
      examined the effects of task characteristics (psychological job demands, job
      control) and social support from the supervisor and colleagues on informal on-the
      job learning among 1588 managers in the Dutch home-care sector. A regression
      analysis revealed that high demands, high control, and high colleague and
      supervisor support were each associated with high levels of informal learning.
      The authors found no evidence for statistical interactions among the effects of
      these concepts. They concluded that to promote managers' informal workplace
      learning, employers should especially increase job control.

PMID- 19157072
TI  - Trust in coworkers and trust in organizations.
AB  - The authors proposed a modified model of organizational trust that incorporates
      trust in 2 foci: coworkers and organizations. They found a relation between the 2
      foci. The authors also found that trust in organizations mediates the relation
      between trust in coworkers and organizational outcomes of affective commitment
      and performance. These findings suggest that it would be meaningful to examine
      the relations between other foci of trust to better understand how different
      domains interact and how such exchanges eventually lead to desired organizational
      outcomes.

PMID- 19157073
TI  - Effect of humor on interpersonal attraction and mate selection.
AB  - The authors examined whether different levels of sense of humor would influence
      respondents' ratings about a potentially desirable partner. The authors used
      vignettes to predict that the targets who possessed a good sense of humor would
      receive significantly higher ratings in measures of attractiveness and
      suitability as a long-term partner than would those who possessed an average or
      no sense of humor. In an experimental design--with gender and humor as
      independent variables and level of attractiveness and suitability as a long-term
      partner as dependent variables--the authors analyzed the data using a
      multivariate analysis of variance. Results show that the targets with a good
      sense of humor received significantly higher ratings of attractiveness and
      suitability than did those with an average or no sense of humor. Furthermore,
      male participants rated female targets as significantly more attractive than
      female participants rated male targets. The authors found no significant
      interaction between gender and humor.

PMID- 19157074
TI  - Peer victimization, rumination, and problem solving as risk contributors to
      adolescents' depressive symptoms.
AB  - The author examined the integration of 2 studies of literature on the development
      of depressive symptoms in adolescents, addressing ruminative coping styles and
      peer victimization. In particular, the author tested whether increasing levels of
      victimization and rumination along with perceived problem solving skills in
      Turkish adolescents are predictive of depressive symptoms. Participants were 250
      adolescents between the ages of 13 and 18 years. The author conducted
      hierarchical multiple regression analyses to examine the joint and separate
      predictive power of problem solving, rumination, and victimization on depressive
      symptoms on each gender. The results of the analyses indicate that rumination
      accounts for a significant fraction of depressive symptoms on both genders.
      However, victimization made a significant contribution to the depressive symptoms
      only for boys. The author found no interaction effect on depressive symptoms and
      discusses the results in light of related literature.

PMID- 19157075
TI  - Construct dimensionality of engagement and its relation with satisfaction.
AB  - Engagement--a persistent and positive affective-motivational state of fulfillment
      characterized by vigor, dedication, and absorption (W. B. Schaufeli, M. Salanova,
      V. Gonzalez-Roma, & A. B. Bakker, 2002)--has become a popular subject among
      academic and industry researchers. Following suggestions in the recent literature
      calling for further examination of the underlying factors comprising the
      construct of engagement, the authors investigated the factor structure of W. B.
      Schaufeli et al.'s measure of engagement and academic engagement's relation to
      academic satisfaction. Previous researchers found a 3-factor structure of
      engagement that comprises vigor, dedication, and absorption. The authors
      administered to a sample of university students a questionnaire on their level of
      engagement in academic work and various other measures. The results did not
      confirm the 3-factor structure. The present authors found engagement and
      satisfaction to be highly related constructs.

PMID- 19157076
TI  - Protein structure, stability, and interactions. Preface.

PMID- 19157077
TI  - Microcalorimetry of proteins and their complexes.
AB  - Ultrasensitive microcalorimetric techniques for measuring the heat capacities of
      proteins in dilute solutions over a broad temperature range (DSC) and the heats
      of protein reactions at fixed temperatures (ITC) are described and the methods of
      working with these instruments are considered. Particular attention is paid to
      analyzing the thermal properties of individual proteins, their stability, the
      energetics of their folding, and their association with specific macromolecular
      partners. Use of these calorimetric methods is illustrated with examples of small
      compact globular proteins, small proteins having loose noncompact structure,
      multidomain proteins, and protein complexes, particularly with DNA.

PMID- 19157078
TI  - Determining the conformational stability of a protein using urea denaturation
      curves.
AB  - The stability of globular proteins is an important factor in determining their
      usefulness in basic research and medicine. A number of environmental factors
      contribute to the conformational stability of a protein, including pH,
      temperature, and ionic strength. In addition, variants of proteins may show
      remarkable differences in stability from their wild-type form. In this chapter,
      we describe the method and analysis of urea denaturation curves to determine the
      conformational stability of a protein. This involves relatively simple
      experiments that can be done in a typical biochemistry laboratory, especially
      when using ordinary spectroscopic techniques to follow unfolding.

PMID- 19157079
TI  - Defining the stability of multimeric proteins.
AB  - The practical application of scanning calorimetry and spectroscopic methods to
      measure the stability of multimeric proteins is described. Oligomeric proteins
      are stabilized by both the intrinsic folding energy of the subunits as well as
      interactions between the subunits. Oligomerization results in a concentration
      dependence for multimer stability, which increases logarithmically with
      increasing concentration. Since the increase in stability does not plateau at
      high protein concentrations, the effect of concentration must be described
      quantitatively. Straightforward mathematical methods are provided for deriving
      the appropriate models for multimer unfolding, and methods are presented for
      analyzing equilibrium unfolding data and stability using the models.

PMID- 19157080
TI  - Protein-protein and ligand-protein interactions studied by analytical
      ultracentrifugation.
AB  - All biological processes involve molecular interactions that result in either
      binding, self-association, or hetero-associations of one form or another. It is
      important to understand that no interactions are completely all-or-none. Some
      approach all-or-none only when there is strong positive cooperativity. Examples
      will be given of typical biomolecular interactions and their expected dependence
      on concentration, in order to point out the relatively wide range of
      concentration over which these types of phenomena take place. This chapter is
      concerned both with the binding of low-molecular-weight ligands to macromolecules
      as well as interactions between macromolecules using analytical
      ultracentrifugation (AUC) as a tool for measuring association properties of these
      systems. The theory of sedimentation of both ideal and nonideal interacting and
      noninteracting systems is discussed. Examples are given of each type of system
      along with a discussion of how each type of system can be analyzed. Several
      methods of data analysis are discussed.

PMID- 19157081
TI  - Monitoring molecular interactions by NMR.
AB  - The ability of proteins to interact with small molecules or other proteins is
      essential in all aspects of biology. In many cases these interactions cause
      detectable changes in NMR chemical shifts, lineshapes, and relaxation rates and
      therefore provide a means by which to study these biologically important
      phenomena. Here we review the theory upon which this analysis is based, provide
      several illustrative examples, and highlight potential problems in the study of
      binding interactions by solution NMR.

PMID- 19157082
TI  - Ligand-binding interactions and stability.
AB  - The reversible interaction or binding of ligands to biological macromolecules is
      fundamental to nearly every aspect of biochemistry and cell biology. Binding
      events typically do not occur in isolation in biochemistry, and are almost always
      coupled or linked to other reactions such as protonation changes, other ligand
      binding interactions, structural transitions, and folding. It is rarely
      sufficient to simply state that something binds. An understanding of binding
      requires a measure of affinity, stoichiometry, and the contributions of linked
      reactions. Emphasis is placed here on defining binding and the influence of
      linkage on binding and stability using both spectroscopic and calorimetric data.

PMID- 19157084
TI  - Quantifying the roles of water and solutes (denaturants, osmolytes, and
      Hofmeister salts) in protein and model processes using the solute partitioning
      model.
AB  - Salts and uncharged solutes in aqueous solution exert effects on a wide range of
      processes in which large amounts ofbiopolymer surface are buried or exposed
      (folding/unfolding, complexation/dissociation, or precipitation/dissolution). A
      simple two-state solute partitioning model (SPM, where the solute is partitioned
      between the bulk and surface water) allows the interpretation and prediction of
      the thermodynamic effects of various uncharged solutes (e.g., urea, glycine
      betaine) on protein and nucleic acid processes in terms of structural
      information. The correlation of solute effects with various coarse-grained types
      of biopolymer surface exposed or buried in a process provides a novel probe for
      investigation of large-scale conformational changes. Solutes that are fully
      excluded from one or more types of biopolymer surface are useful to quantify
      changes in water of hydration of these surfaces in biopolymer processes.
      Additionally, application of the SPM to the analysis of non-Coulombic salt
      effects on various model processes provides an estimate for the hydration layer
      at surfaces and shows that ion effects are additive and independent of the nature
      of the counterion.

PMID- 19157083
TI  - A method for direct measurement of protein stability in vivo.
AB  - The stability of proteins is tuned by evolution to enable them to perform their
      cellular functions for the success of an organism. Yet, most of the arsenal of
      biophysical techniques at our disposal to characterize the thermodynamic
      stability of proteins is limited to in vitro samples. We describe an approach
      that we have developed to observe a protein directly in a cell and to monitor a
      fluorescence signal that reports the unfolding transition of the protein,
      yielding quantitatively interpretable stability data in vivo. The method is based
      on incorporation of structurally nonperturbing, specific binding motifs for a bis
      arsenical fluorescein derivative in sites that result in dye fluorescence
      differences between the folded and unfolded states of the protein under study.
      This fluorescence labeling approach makes possible the determination of
      thermodynamic stability by direct urea titration in Escherichia coli cells. The
      specific case study we describe was carried out on the predominantly beta-sheet
      intracellular lipid-binding protein, cellular retinoic acid-binding protein
      (CRABP), expressed in E. coli.

PMID- 19157085
TI  - Molecular crowding and solvation: direct and indirect impact on protein
      reactions.
AB  - The typical environment for biomolecules in vivo is highly crowded. Under such
      conditions chemical activities, rather than simply concentrations, govern the
      behavior of the molecules. In this chapter we discuss the underlying solvation
      principles that give rise to the chemical activities. We focus on simple
      experimentally accessible examples, macromolecular crowding, protein folding, and
      ligand binding under crowded conditions. We discuss effects of high
      concentrations of both macromolecules and small molecules in terms of the
      Kirkwood-Buff theory, which couples solution structure to thermodynamics.

PMID- 19157086
TI  - Defining the role of salt bridges in protein stability.
AB  - Although the energetic balance of forces stabilizing proteins has been
      established qualitatively over the last decades, quantification of the energetic
      contribution of particular interactions still poses serious problems. The reasons
      are the strong cooperativity and the interdependence ofnoncovalent interactions.
      Salt bridges are a typical example. One expects that ionizable side chains
      frequently form ion pairs in innumerable crystal structures. Since electrostatic
      attraction between opposite charges is strong per se, salt bridges can
      intuitively be regarded as an important factor stabilizing the native structure.
      Is that really so? In this chapter we critically reassess the available methods
      to delineate the role ofelectrostatic interactions and salt bridges to protein
      stability, and discuss the progress and the obstacles in this endeavor. The basic
      problem is that formation of salt bridges depends on the ionization properties of
      the participating groups, which is significantly influenced by the protein
      environment. Furthermore, salt bridges experience thermal fluctuations,
      continuously break and re-form, and their lifespan in solution is governed by the
      flexibility of the protein. Finally, electrostatic interactions are long-range
      and might be significant in the unfolded state, thus seriously influencing the
      energetic profile. Elimination of salt bridges by protonation/deprotonation at
      extreme pH or by mutation provides only rough energetic estimates, since there is
      no way to account for the nonadditive response of the protein moiety. From what
      we know so far, the strength of electrostatic interactions is strongly context
      dependent, yet it is unlikely that salt bridges are dominant factors governing
      protein stability. Nevertheless, proteins from thermophiles and hyperthermophiles
      exhibit more, and frequently networked, salt bridges than proteins from the
      mesophilic counterparts. Increasing the thermal (not the thermodynamic) stability
      of proteins by optimization of charge-charge interactions is a good example for
      an evolutionary solution utilizing physical factors.

PMID- 19157087
TI  - Protein stabilization by the rational design of surface charge-charge
      interactions.
AB  - The design of proteins with increased stability has many important applications
      in biotechnology. In recent years, strategies involving directed evolution,
      sequence-based design, or computational design have proven successful for
      generating stabilized proteins. A brief overview of the various methods that have
      been used to increase protein stability is presented, followed by a detailed
      example of how the rational design of surface charge-charge interactions has
      provided a robust method for protein stabilization.

PMID- 19157088
TI  - NMR analysis of native-state protein conformational flexibility by hydrogen
      exchange.
AB  - The rate of hydrogen exchange for the most protected amides of a protein is
      widely used to provide an estimate of global conformational stability by
      analyzing the exchange kinetics in the unfolded state in terms of model peptide
      exchange rates. The exchange behavior of the other amides of the protein which do
      not exchange via a global unfolding mechanism can provide insight into the
      smaller-scale conformational transitions that facilitate access to solvent as
      required for the exchange reaction. However, since the residual tertiary
      structure in the exchange-competent conformation can modulate the chemistry of
      the exchange reaction, equilibrium values estimated from normalization with model
      peptide rates are open to question. To overcome this limitation, the most robust
      approaches utilize differential analyses as a function of experimental variables
      such as denaturant concentration, temperature, pH, and mutational variation.
      Practical aspects of these various differential analysis techniques are
      considered with illustrations drawn from the literature.

PMID- 19157089
TI  - Single-molecule fluorescence studies of protein folding.
AB  - The structural and dynamic details of protein folding are still widely unexplored
      due to the enormous level of heterogeneity intrinsic to this process. The
      unfolded polypeptide chain can assume a vast number of possible conformations,
      and many complex pathways lead from the ensemble of unfolded conformations to the
      ensemble of native conformations in an overall funnel-shaped energy landscape.
      Classical experimental methods involve measurements on bulk samples and usually
      yield only average values characteristic of the entire molecular ensemble under
      study. The observation of individual molecules avoids this averaging and allows,
      in principle, microscopic distributions of conformations and folding trajectories
      to be revealed. Fluorescence-based techniques are arguably the most versatile
      single-molecule methods at present, and Forster resonance energy transfer (FRET)
      between two dye molecules specifically attached to the protein of interest
      provides a means of studying the inter-dye distance and, thereby, the
      conformation of folding polypeptide chains in real time. This chapter focuses on
      practical aspects and different experimental realizations for protein folding
      investigations by using single-molecule fluorescence.

PMID- 19157090
TI  - Experimental characterization of the denatured state ensemble of proteins.
AB  - The traditional view of the denatured state ensemble of proteins is that it
      behaves as a classic random coil. This model has important implications for the
      analysis of protein stability, protein folding, and cooperativity; namely that
      the effects of mutations on the free energy of the denatured state ensemble can
      be ignored. This assumption, which is still routinely made, at least at the
      implicit level, greatly simplifies the analysis of such experiments. However it
      has long been recognized that the denatured state ensemble (DSE) of real proteins
      is often quite different from a random coil and can exhibit significant
      structural preferences. In some cases parts of the chain can even adopt
      relatively well-defined conformations, particularly under native conditions. Well
      studied examples of DSE interactions include elements of hydrogen-bonded
      secondary structure, particularly helices or turns, as well hydrophobic clusters,
      hydrophobic aromatic clusters, and more recently interactions involving charged
      residues. Deviations from random-coil behavior are of practical importance if
      they influence protein folding, stability, or function, or if they compromise our
      analysis and interpretation of experiments. The existence of residual structure
      in the DSE naturally leads to the question of its role in protein folding and
      stability, and raises the possibility that some mutations could exert a
      significant part of their effect by altering the DSE. Much of our understanding
      of the interactions governing protein stability and the folding process have been
      generated by mutational studies; thus, a detailed understanding of the denatured
      state ensemble is critical.

PMID- 19157091
TI  - [Etiological diagnosis and management of hemospermia].
AB  - Hemospermia refers to the macroscopic presence of blood in semen, which may be
      associated with male genital tract, lower urinary tract and systemic diseases.
      Hemospermia is prevalent in young males. It is mostly a benign lesion and self
      limited symptom, requiring only basic investigations and simple management. But
      in a few patients, it may be the primary symptom of urogenital malignancy.
      Therefore in patients older than 40 years, or in those with persistent or
      recurrent hemospermia, further investigation should be conducted by imaging and
      endoscopic examinations to make definite etiological diagnosis and give
      corresponding treatment. This article reviews the etiology, initial diagnostic
      workup, imaging techniques and endoscopic examination of hemospermia, and
      summeries its management.

PMID- 19157092
TI  - [Expressions of VEGF and Flt-1 in the testis, epididymis and epididymal sperm of
      adolescent rats].
AB  - OBJECTIVE: To study the expressions of the vascular endothelial growth factor
      (VEGF) and its receptor fms-like tyrosine kinase-1 (Flt-1) in the testis,
      epididymis and epididymal sperm of adolescent rats and explore the functions of
      both the proteins in the male reproductive system. METHODS: The expressions of
      VEGF and Flt-1 were detected in 20 adolescent SD rats, immunohistochemical
      staining used for both the testis and the epididymis and immunofluorescent
      staining for sperm. RESULTS: VEGF and Flt-1 proteins were specifically present in
      the testis, epididymis and sperm. In the testis, VEGF immunoreactive particles
      were localized in the cytoplasm of spermatogenic cells, the developing acrosome
      of spermatids, Sertoli cells and Leydig cells, while Flt-1 expressed mainly in
      the developing acrosome of spermatids and Leydig cells. In the epididymis, the
      cell-specific and region-specific expressions of VEGF and Flt-1 proteins were
      observed in the principal cells of epididymal epithelia, VEGF in the whole
      epididymis, while Flt-1 only in the caput and cauda segments. Both VEGF and Flt-1
      were localized in the acrosome of the sperm head as well as in the neck, middle
      and principal segments of the sperm tail. CONCLUSION: The specific expression
      patterns of VEGF and Flt-1 in the rat testis, epididymis and sperm indicate that
      they may independently or collectively affect spermatogenesis and spermiotelcosis
      in either an autocrinological or a

PMID- 19157093
TI  - [Growth factors promote the survival and proliferation of human spermatogonium
      stem cells in vitro].
AB  - OBJECTIVE: To study the effects of growth factors on the survival and
      proliferation of human spermatogonial stem cells (SSCs) in vitro. METHODS: SSCs
      were treated with the growth factors SCF, LIF and bFGF added to the culture, each
      at the concentrations of 0, 5, 10 and 20 microg/L and repeated three times. The
      survival time and proliferation rate of the cells were determined every 8-12
      hours and their morphological features observed with the light microscope and
      electron microscope. RESULTS: The survival time and proliferation rate of the
      SSCs were significantly increased in the treated groups as compared with the
      control (P < 0.05). CONCLUSION: The growth factors SCF, LIF and bFGF can promote
      the survival and proliferation of SSCs in vitro.

PMID- 19157094
TI  - [Loss of heterozygosity on chromosome 10 is associated with bone metastasis of
      human prostate cancer].
AB  - OBJECTIVE: To study the cytogenetic mechanism of bone metastasis of human
      prostate cancer (PCa). METHODS: We analyzed chromosome variation by comparative
      genomic hybridization in 18 patients with prostate cancer to determine the
      chromosome variants associated with bone metastasis, and focused on 7
      microsatellite sites on chromosome 10 for the detection of the loss of
      heterozygosity (LOH) by PCR-based microsatellite polymorphism analysis. RESULTS:
      In the 11 samples with bone metastasis, the variation rate of chromosome 10 was
      90.9% (10/11), significantly higher than that of the others (P < 0.01). A much
      higher LOH frequency was observed at the 7 microsatellite loci on chromosome 10
      and the highest located in 10q24. 2-q25.3 (D10S1693-D10S587) in the PCa patients
      with bone metastasis. CONCLUSION: There is a high-frequency LOH region in 10q24.
      2-q25.3 (D10S1693-D10S587) on chromosome 10 in PCa patients with bone metastasis,
      which may be potentially involved in PCa progression and specific bone
      metastasis.

PMID- 19157095
TI  - [Human chorionic gonadotrophin regulates epidermal growth factor in the phallus
      of hypospadias mice].
AB  - OBJECTIVE: To investigate the etiopathogenesis of congenital hypospadias and the
      regulating effect of exogenous human chorionic gonadotrophin (hCG) on the
      epidermal growth factor (EGF) in the phallus of hypospadiac mice. METHODS: Mouse
      models of congenital hypospadias were established. Fifty healthy male mice
      randomly selected as normal controls received intraperitoneal injection of normal
      saline, and another 50 with hypospadias were equally divided into an experimental
      control group, intraperitoneally injected with 1 ml normal saline, and 4 hCG dose
      groups treated by hCG intraperitoneal injection at 50 IU, 100 IU, 150 IU and 200
      IU respectively for 7 consecutive days. The concentrations of EGF in the phallus
      and serum were detected in different groups by ELISA. RESULTS: The concentrations
      of EGF in the phallus were significantly lower in the hypospadias rats than in
      the normal controls (P < 0.05), the 150 IU and 200 IU hCG groups showing
      significant differences from the 50 IU, 100 IU and experimental control groups (P
      < 0.05), as the 50 IU, 100 IU and experimental control groups from the normal
      control (P < 0.05). But no obvious difference was found in EGF concentration in
      the serum among different groups (P > 0.05). CONCLUSION: Nonsteroidal
      antiandrogen and decreased concentration of EGF in the mouse phallus may be
      associated with the etiology of hypospadias. And exogenous hCG at 150 IU or 200
      IU can increase the concentration of EGF in the phallus of mice with congenital
      hypospadias.

PMID- 19157096
TI  - [Development of a novel protein carrier inducing immune response and binding DNA
      in gene therapy].
AB  - OBJECTIVE: To develop a novel protein carrier which can not only regulate the
      immune system but also deliver DNA into the tumor cell as an effective non-viral
      gene delivery system. METHODS: By using gene engineering techniques, we
      constructed a fusion protein containing the -COOH end of human hepatitis B virus
      core antigen (HBcAg), small home-to-cancer peptide ligand RGD and Glutathione S
      transferase (GST), which was expressed in E. coli and purified by size exclusion
      chromatography and affinity chromatography. We labeled it with FITC to observe
      whether it could bind prostate cancer PC-3 cell lines, and meanwhile used it as a
      non-viral gene delivery carrier with the plasmid pEGFP-N1 that could express GFP
      in PC-3 cells. Furthermore, we observed the regulatory function of this fusion
      protein to the mouse immune system. RESULTS: The results of SDS-PAGE showed that
      the new protein carrier was obtained, which It could enter PC-3 cells with DNA in
      vitro and induce the mouse immune system to produce IgG1 and IgG2alpha
      simultaneously. CONCLUSION: The new protein carrier can be used as a target
      protein, especially in positive cells and the immune system. It promises to be a
      good novel carrier for the gene therapy of cancer.

PMID- 19157097
TI  - [Applied anatomical study of the penile deep venous system].
AB  - OBJECTIVE: To investigate the run and distribution of penile deep veins and to
      evaluate the application of the findings to penile vein ligating operation.
      METHODS: We dissected the penises of 28 formalin-preserved male adult cadavers,
      whose health condition, penile erection condition when alive, exact age and cause
      of death were unknown, and recorded the number and location of the cavernous and
      crural veins and their relationship with the surrounding important organs and
      tissues. RESULTS: The cavernous veins emerged from the dorsal groove of the fixed
      segment, ran proximately in the dorsal groove, branched into two and drained into
      either side of the internal pudendal vein respectively, with the internal
      pudendal artery-cavernous artery-dorsal artery system running laterally and
      superficially. All the cavernous veins had communications with the periprostatic
      venous plexus. In the 56 crura of the 28 specimens, there were 250 crural veins,
      76 in 42 sides (75.0%) traveling medial to the internal pudendal artery-cavernous
      artery-dorsal artery system. CONCLUSION: The penile deep venous system is
      structurally complicated, extensively connected with the surrounding veins and
      closely related to the surrounding organs, which makes it very difficult to
      ligate all the deep veins and avoid damage to the cavernous arteries and nerves
      in vein-involved surgery.

PMID- 19157098
TI  - [Selective serotonin reuptake inhibitor is more likely to induce sexual
      dysfunction than mirtazapine in treating depression].
AB  - OBJECTIVE: To compare the incidences of sexual dysfunction induced by mirtazapine
      and SSRI in the treatment of patients with depression. METHODS: Using key-word
      retrieval from the compact disks of the Chinese biological medicine (CBM) data
      base, we analyzed the rates of sexual dysfunction from the published clinical
      control trials on depression treated with mirtazapine and SSRI by applying the
      fixed effects model (FEM) of evidence-based medicine (EBM). RESULTS: Among 1108
      cases in 14 studies, there were 5 cases of mirtazapine-induced and 106 cases of
      SSRI-induced sexual dysfunction, accounting for 0.90% and 19.2% respectively, OR
      = 0.07 (95% CI: 0.04-0.14), Z = 8.03, P < 0.01. CONCLUSION: SSRI is far more
      likely to induce sexual dysfunction than mirtazapine in the treatment of
      depression.

PMID- 19157099
TI  - [Clinical analysis of surgically treated cervical spondylotic myelopathy with
      erectile dysfunction].
AB  - OBJECTIVE: To investigate the recovery of sexual function of surgically treated
      male patients with cervical spondylotic myelopathy. METHODS: A prospective and a
      mean 16-month postoperative follow-up were conducted for 22 male patients
      surgically treated for cervical spondylotic myelopathy complicated by sexual
      dysfunction. Their neurologic scores were obtained by the Japanese Orthopedic
      Association (JOA) Scoring System, their sexual function assessed by the
      International Index of Erectile Function (IIEF), and their pre- and post
      operative reflexogenic and psychogenic erection analyzed by comparison. RESULTS:
      Most of the patients experienced an obvious improvement in neurological function
      after the surgery, with a significantly higher JOA score than pre-operation ( P <
      0.01). Compared with the preoperative rates of abnormal reflexogenic and
      psychogenic erection, 82% (18/22) and 18% (4/22) , the average IIEF score was
      elevated from preoperatively (9.90 +/- 2. 22) to postoperatively (20.89 +/-
      3.89), with a statistically significant difference (P < 0.01). CONCLUSION:
      Cervical spondylotic myelopathy induces sexual as well as neurological
      dysfunction, mostly with abnormal psychogenic but normal reflexogenic erection.
      With neurological recovery, most of the patients may experience an improvement in
      their sexual function after surgery.

PMID- 19157100
TI  - [Sexual physiology and psychology of male college students and their clinical
      significance].
AB  - OBJECTIVE: To understand the sexual physiology and psychology of male college
      students and to provide schools, families and the society with reference for the
      sexual physiological and psychological education among college students as well
      as for the diagnosis and treatment of their sexual psychological disorders in
      Jiangsu. METHODS: An investigation was conducted by using a questionnaire on
      sexual physiology and psychology among randomly selected 3786 male college
      students from 18 universities in Jiangsu. RESULTS: As regards sexual education,
      5.49% of the subjects were satisfied with their schools, 78.18% wanted it to be
      strengthened and 68.36% obtained their sexual knowledge from the internet.
      Concerning sexual physiology, 68.78% experienced their first spermatorrhea at the
      age of 12-15. As for sexual psychology, 85.79% loved a certain female inwardly,
      and 70.99% experienced love affairs. With regard to sexual activity, 25.54% had
      sexual experience. CONCLUSION: College students nowadays are relatively open in
      sexual ideology, immature in sexual psychology and lacking in sexual knowledge,
      while schools are inefficient in sexual education. Their sexual health calls for
      joint attention from schools, families and the society, particularly schools,
      which need to establish special offices for research and education on sexual
      health.

PMID- 19157101
TI  - [TUBVP and HOLEP: desirable surgical options for large benign prostatic
      hyperplasia ( >80 ml)].
AB  - OBJECTIVE: To compare the safety and efficacy of the two surgical alternatives,
      transurethral bipolar vaporization resection of the prostate (TUBVP) and holmium
      laser enucleation of the prostate (HOLEP), in the treatment of large benign
      prostatic hyperplasia (BPH). METHODS: Retrospective analyses were made of 56
      cases of large BPH ( >80 ml), 34 treated by TUBVP with the Bipolar Vaporization
      System (ACMI Medical Ltd, U.K.) at 160 W in cutting and 80 W in coagulation mode,
      and 22 by HOLEP with the Holmium Laser System (LUMNIS Ltd, US) at 100W. The
      safety and efficacy of the two approaches were assessed based on the operative
      and follow-up data. RESULTS: Blood loss was significantly less in the HOLEP than
      in the TUBVP group ( P < 0.01), but the time of postoperative bladder irrigation
      and catheter indwelling was obviously shorter in the latter. IPSS, Qmax and
      Residual unine were markedly improved at 1 and 3 months after the surgery, with
      no statistically significant differences between the two groups. CONCLUSION: Both
      TUBVP and HOLEP are safe and effective surgical options for the treatment of
      large BPH. Particularly the former, easier to be popularly applied, is promising
      to be a new "gold standard" in the surgical treatment of BPH.

PMID- 19157102
TI  - [Efficacy and safety of vardenafil for kidney transplant recipients with erectile
      dysfunction].
AB  - OBJECTIVE: To evaluate the efficacy and safety of vardenafil in kidney transplant
      recipients with erectile dysfunction. METHODS: Thirty-nine kidney transplant
      recipients with erectile dysfunction (ED) and serum creatinine values <2 mg/dl
      were enrolled in a 4-week randomized, double blind, placebo-controlled study, 19
      treated with placebo and 20 with vardenafil. Vardenafil efficacy was assessed
      with the IIEF questionnaire after 4 weeks of treatment, and its safety appraised
      by measuring serum creatinine levels, creatinine clearances and cyclosporine
      concentrations before and after the treatment. RESULTS: IIEF scores improved from
      12.6 +/- 3.4 to 26.5 +/- 2.8 (P < 0.01), but renal function and cyclosporine
      concentrations remained unchanged in the vardenafil-treated patients. Adverse
      effects were observed in 4 patients: headache in 2, palpitation and flush in 1,
      and dyspepsia in the other. CONCLUSION: Oral vardenafil therapy has a high
      efficacy and a low incidence of adverse events for kidney transplant recipients
      with ED.

PMID- 19157103
TI  - [Semen analysis of sterile patients among occupational computermen].
AB  - OBJECTIVE: To explore temn possible correlation between the computer occupational
      semen quality. METHODS: We included in this study 224 sterile males (118
      computermen and 106 non-computermen) treated in our clinic of male sterility and
      125 normal fertile men as controls, and analyzed such parameters as semen
      liquefaction time and sperm density, vitality and motility according to the WHO
      standard. RESULTS: Compared with the normal controls, there was a significant
      decrease in the semen volume and sperm density, vitality and motility (P < 0.05
      0.01) and a marked increase in liquefaction time in the infertile computermen and
      non-computermen (P < 0.01). The semen volume and sperm vitality and motility were
      significantly lower in the infertile computermen than in the infertile non
      eomputermen (P < 0.05). The three parameters were also significantly decreased in
      the 0-5, 6-10 and > 10 h/d computer use groups. Similarly, significantly lower
      sperm density, vitality and motility were observed in the > 10 hid group than in
      the 0-5 and 6-10 h/d groups (P < 0.05-0.01), but with no statistical difference
      between the latter two (P > 0.05). CONCLUSION: Computer occupation is associated
      with abnormal semen quality, and long-term computer use ( > 10 h/d) may be one of
      the factors of male infertility.

PMID- 19157104
TI  - [Diagnosis and treatment of isolated tuberculous epididymitis].
AB  - OBJECTIVE: To improve the diagnosis and the treatment of tuberculous
      epididymitis. METHODS: Retrospective studies were made of 20 cases of isolated
      epididymal tuberculosis defined as "tuberculosis infection affecting the
      epididymis without evidence of renal involvement as documented by the absence of
      acid fast bacilli in the urine sample and on imaging" among 35 patients with
      epididymal tuberculosis. Two weeks after the intensified anti-TB treatment by the
      combined therapy of Isoniazid + Rifampicin + Streptomycin or Ethambutol, all the
      patients underwent surgical removal of the tuberculous lesion, followed again by
      the combined therapy for 6-9 months. RESULTS: Of the 20 cases, 16 experienced no
      recurrence and complications within 0.5-5 years after the surgery, 3 were found
      with urinary tuberculosis at 3, 3.5 and 5 years, and 1 developed tuberculous
      epididymitis of the other side at 3.5 years. CONCLUSION: Isolated tuberculous
      epididymitis may be the sole or the initial presentation of genitourinary
      tuberculosis, for which timely surgery is the best option and has a good
      prognosis.

PMID- 19157105
TI  - [Perioperative treatment of senile benign prostatic hyperplasia patients
      undergoing transurethral electrovaporization of prostate].
AB  - OBJECTIVE: To investigate the perioperative treatment of senile patients with
      benign prostatic hyperplasia (BPH) undergoing transurethral electrovaporization
      of prostate (TUEVP). METHODS: Totally 131 BPH patients aged 75-88 years underwent
      TUEVP, general data and past history of illness of the patients obtained before
      surgery, including their mental state, self-care ability, diseases of the
      cardiovascular, cerebrovascular and respiratory systems, diabetes mellitus,
      thyroid diseases and medication, and preoperative routine examinations performed
      on the functions of the kidneys, lungs, heart and thyroid gland to assess their
      operation-endurance, chances of complications and perioperative countermeasures.
      RESULTS: Of the total number of patients, 128 recovered urination and 3 relapsed
      into urinary retention after withdrawal of the catheter, with 2 restored to
      health. One patient had to carry the stomal tube because of bladder contraction
      dysfunction, 2 (1.5%) developed secondary bleeding but recovered after
      conservative treatment, 1 (0.7%) deep vein thrombus, 1 acute hemorrhagic
      gastritis (0.7%) and 4 (3.0%) postoperative urinary tract infection, but with no
      TUEVP syndrome and no complications of the cerebrovascular and respiratory
      systems. A 3-6 months follow-up showed that IPSS decreased from 25.24 +/- 4.70 to
      7.81 +/- 4.12, QOL dropped from 4.51 +/- 0.72 to 1.51 +/- 0.73, and Qmax
      increased from (10.14 +/- 6.31) ml/s to (18. 14 +/- 4. 12) ml/s. CONCLUSION: By
      proper perioperative treatment, TUEVP could be safely and smoothly performed in
      senile BPH patients, with fewer complications and better recovery.

PMID- 19157106
TI  - [Comparison of the parameters obtained by sperm quality analyzer V and computer
      aided sperm analysis system].
AB  - OBJECTIVE: To assess the differences between the main parameters obtained by
      sperm quality analyzer V (SQA-V) and computer-aided sperm analysis system (CASA),
      and to investigate their application to sperm quality analysis for fertile and
      infertile men. METHODS: Twelve fresh semen samples from fertile volunteers and 73
      from infertility patients were detected with SQA-V and CASA for sperm
      concentration and motility, the percentage and concentration of motile sperm,
      sperm motility index (SMI), amplitude of lateral head displacement (ALH), beat
      cross frequency (BCF), curvilinear velocity (VCL), straight line velocity (VSL),
      average path velocity (VAP), linearity (LIN = VSL/VCL) and straightness (STR =
      VSL/VAP). The correlation between the parameters obtained by the two devices were
      analyzed. RESULTS: Significant differences were observed in the above parameters
      between the fertile and infertile groups. An obvious consistency was noted
      between the results from SQA-V and those from CASA in sperm concentration (r =
      0.58, P < 0.01), motile sperm concentration (r = 0.75, P < 0.01) and average
      sperm velocity (r = 0.59, P < 0.01). Significant correlations were found between
      the SMI from SQA-V and STR, LIN, BCF, VCL, VSL and VAP from CASA (P < 0.05).
      CONCLUSION: There is a consistency between the results from SQA-V and those from
      CASA. Both the devices can detect the seminal differences between different
      cohorts of patients.

PMID- 19157107
TI  - [Effectiveness and safety of naftopidil for benign prostatic hyperplasia patients
      with overactive bladder symptoms].
AB  - OBJECTIVE: To assess the effectiveness and safety of the alphala/d blocker
      naftopidil in the treatment of benign prostatic hyperplasia (BPH) patients with
      overactive bladder (OAB) symptoms. METHODS: Fifty BPH patients with OAB symptoms
      were treated with naftopidil at the dose of 25 mg/d for 6 weeks. A self
      controlled clinical trial was conducted. The effectiveness and safety of the drug
      were observed by comparing the International Prostate Symptom Scores (IPSS),
      quality of life indexes (QOL), maximum urinary flow rates (Qmax) , average
      urinary flow rates (Qave), voiding volumes (VV), blood pressures (BP) and heart
      rates (HR) obtained before and after the treatment. RESULTS: After 6 weeks'
      medication, the 46 assessable cases showed an average decrease of 9.75 in IPSS (P
      < 0.01), 3.97 in voiding symptom score (P < 0.01), 5.78 in urinary storage
      symptom score (P < 0.01) and 1.95 in QOL (P < 0.01), and a mean increase of 4.29
      ml/s in Qmax (P < 0.01), 3.75 ml/s in Qave (P < 0.01) and 55.12 ml/s in VV (P <
      0.05). But no significant changes were observed in BP and HR. Only 1 patient
      (4.35%) experienced the adverse event of dizziness. CONCLUSION: The alphalA/D
      blocker naftopidil is both effective and safe in the treatment of BPH patients
      with OAB symptoms.

PMID- 19157108
TI  - [Update of gene therapy for aging-related erectile dysfunction].
AB  - The incidence of erectile dysfunction (ED) rises with the increase of age, for
      which gene therapy is a new option in the recent years. Different target genes,
      vehicles and therapeutic strategies have been tried and yielded good results.
      This paper offers an overview of the current advances in gene therapy for aging
      related ED.

PMID- 19157109
TI  - [Association of mating type switching/sucrose non-fermenting complex with
      prostate cancer].
AB  - ATP-dependent chromatin remodeling by the mating type switching/sucrose non
      fermenting (SWI/SNF) complex is a basic biological event in the body, which is
      required for all the key processes involved in DNA metabolism such as gene
      expression, DNA replication, repair, chromosomal recombination and mitosis. In
      the past few years, increasing evidence supports a crucial role of this complex
      in prostate cancer development and progression via multiple ways, such as cell
      cycle regulation, androgen receptor pathway and DNA methylation. The present
      paper briefly reviews the recent studies on the association between the SWI/SNF
      complex and prostate cancer.

PMID- 19157110
TI  - [Medicinal treatment of idiopathic male infertility].
AB  - Exact etiological factors of male infertility is called idiopathic male
      infertility. Some breakthroughs have been made in the treatment of the problem
      since the development of ICSI in 1992. However, traditional treatment should also
      be taken into account for individual male infertility. Medication as a
      traditional treatment is still one of the important therapeutic methods. The
      basic understanding of male infertility, the characteristics of its drug therapy,
      clinically used common drugs, the therapeutic efficacy and effect evaluation are
      reviewed in this article.

PMID- 19157111
TI  - [Astragalus protects the testis following testicular torsion/detorsion in rats].
AB  - OBJECTIVE: To investigate the protective effect of astragalus on testis tissues
      following unilateral testicular torsion/detorsion. METHODS: Thirty healthy adult
      Wistar rats were equally randomized into Group A (sham-operation control), B
      (torsion/detorsion) and C (torsion/detorsion plus intraperitoneal injection of
      astragalus). The testicular torsion/detorsion model was established by the Turner
      method. All the rats were fed under the same condition for 7 days and sacrificed,
      and the torsional testes were harvested for the detection of germ cell apoptosis,
      glutathione activity and the level of malonic diethylaldehyde (MDA). RESULTS: The
      apoptosis indexes (AI) of spermatogenic cells in the torsional testes were (5.82
      +/- 1.21), (36.18 +/- 8.40) and (20.39 +/- 3.57) in Group A, B and C,
      significantly higher in Group B and C than in A (P < 0.05) and in Group B than in
      C (P < 0.05). Significant differences were observed in glutathione activity in
      the ipsilateral testes among Group A (48.03 +/- 2.01), B (30.93 +/- 1.25), C
      (38.44 +/- 1.06) U/mg (P< 0.05), as well as in the level of MDA, (1.43 +/- 0.17),
      (3.98 +/- 0.36), (2.57 +/- 0.53) nmol/ml, among the three groups (P < 0.05).
      CONCLUSION: Astragalus could significantly reduce the apoptosis of spermatogenic
      cells, decrease the level of lipid peroxidation and protect glutathione activity
      in the torsional testis.

PMID- 19157112
TI  - [Molecular mechanism and genetic basis of geoherbs].
AB  - As products of interaction of time and space, geoherbs, which are essential parts
      of Chinese Materia Medica, were characterized in different morphology, unique
      habitat, continuous and changeable sites. The main fields in molecular mechanism
      of geoherbs focus on: biodiversity and molecular identification, genetic
      different and evolutionary genetics, geo-variation and environmental adaptation,
      germplasm and aimed genus choosing, expression and control of functional gene,
      gene transfer and bio-safety evaluation. The main tasks are to discover the
      genetic variation at molecular level, ascertain the molecular characteristics of
      geoherbs and the effect of environment on gene expression of geoherbs, confirm
      the genetic factors attribute to the forming of geoherbs, and find out the
      genetic basis of geoherbs at individual level and population level, respectively.
      This paper pointed out that the essential of geoherbs is continuers quantities
      variation at population level, geoherb's populations are different in gene
      frequency with the others'; geohersm are quantitative trait loci (QTL) controlled
      by multi - gene or combination with multiple-gene and major gene at individual
      level. It is very important to pay more attention to the scale effect of
      geoherbs, refer the theories and methods of quantities genetic, and concern more
      about the interaction of environment and gene in geoherbs' molecular mechanism
      research.

PMID- 19157113
TI  - [Study on genetic relationship of official Rheum by SRAP].
AB  - OBJECTIVE: To determine the genetic relationship of three species of official
      Rheum in molecular level. METHOD: Twelve samples from three species of official
      Rheum were employed to be analyzed by the approach of sequence-related amplified
      polymorphism (SRAP). Systematic relationships were constructed based on the UPGMA
      method by TREECONW software. RESULT: A total of 272 bands were scored and 199
      bands of them were polymorphic, which were up to 73.2% polymorphic ratio. Genetic
      similarity coefficient was changed from 0.578 4 to 0.941 6. The results indicated
      that there was abundant genetic diversity among the tested materials. The
      clustering analysis revealed that the results between SRAP marker and the
      traditional morphological characteristics was almost the same. CONCLUSION: SRAP
      marker is suitable for variety identification and genetic relationship research
      in official Rheum.

PMID- 19157114
TI  - [Effects of slow release-fertilizers on yield, nutrient contents and quality of
      Coptis chinensis].
AB  - OBJECTIVE: To study the effects of four kind of slow-release fertilizers on yield
      and quality of Coptis chinensis. METHOD: One to three years C. chinensis was
      fertilized with slow-release fertilizers twice in April and in September. The
      yield and nutrient content along with quality of C. chinensis were measured after
      two years growth. RESULT AND CONCLUSION: All of the slow-release fertilizers
      increased the yield obviously, and the effect of SRF1 and SRF4 is the most
      significant. Comparing with control group, the N content in aerial part of 1-2
      year-old C. chinensis treated with SRF1 and SRF4 was lower and P and K were
      higher than that of control group, and the N content in aerial part of 3 year-old
      C. chinensis treated with SRF1 and SRF4 was higher and P and K were higher than
      that of control group; The N content in the root of land 3 year-old C. chinensis
      treated with SRF1 and SRF4 showed no significant difference comparing with
      control group, and P and K were lower than that of control group, the N and P
      content in root of 2 year-old C. chinensis treated with SRF1 and SRF4 was higher
      and K were lower than that of control group. After two years growth berberine
      content of C. chinensis treated with SRF1, SRF2 and SRF3 were significantly
      increased, and total alkaloid content of C. chinensis treated with SRF1, SRF3 and
      SRF4 were significantly increased. We recommend that SRF4 is used as the special
      fertilizer for 1-year-old C. chinensis, and the SRF1 and SRF4 for 2-year-old C.
      chinensis, and the SRF1 for 3-year-old C. chinensis.

PMID- 19157115
TI  - [Medicinal mammals resources in Yancheng nature reserve, Jiangsu province].
AB  - A preliminary investigation of the medicinal mammals resources was carried out in
      Yancheng nature reserve, Jiangsu province, and the results are as follows: The
      medicinal mammals cover 18 species. Among them, 3 species are listed as the
      national key protection in China, 1 species is in category 1 and 2 species are in
      category 2. Ten species are listed in economic important category and in
      scientific research category. The result of the investigation revealed the
      situation of the medicinal mammals resources in Yancheng nature reserve, Jiangsu
      province, and the suggestions of protection and management about the medicinal
      mammals were proposed in this paper.

PMID- 19157116
TI  - [Decolorization and purification of total leaves saponins of panax notoginseng
      with ion exchange resins].
AB  - The total leaves saponins of panax notoginseng decoloring by adsorption with
      exchange resins was studied and the decoloring capacity of six anions resins as
      adsorbent material was evaluated. The decoloring capacity of the selected resins
      (D296 and Dt) was compared by the dynamic adsorption decolorization experiments.
      Removel of coloured compounds in rew solution takes place in two serially coupled
      different ionic exchange columns, one packed column was D72 cation resin, another
      anion resin. The results showed that macroporous anion exchange resin Dt was the
      best resin to decolorization of the total leaves saponins of panax notoginseng.
      The total saponin products with higher purity and quality were obtained. The
      results of this work shows that the method proposed is convenient, high
      efficcient and steady one.

PMID- 19157117
TI  - [Comparative research on quality of various Shenqu fermentated with different
      pure inoculation].
AB  - OBJECTIVE: Improving the traditional fermentation technology by some unidentified
      strains into the modern pure inoculation fermentation technology. For selecting
      better fermentation strains, the quality of various Shenqu fermentated with
      different pure inoculation be compared. METHOD: Isolating the strains from self
      fermented Shenqu, then with other 2 certain strains, to conduct the pure
      inoculation fermentation. Then compare the quality of them according to the
      difference in the chemical composition, activity of enzyme and the impact to the
      digestive function in mice of the finished Shenqu. RESULTS: Four strains were
      isolated. One of them, a mucor genus of mold is better than others. CONCLUSION:
      Modern pure inoculation fermentation can ensure the quality and the medication
      safety of Shenqu. New fermentation technology is feasible.

PMID- 19157118
TI  - [HPLC determination of chemical constituents produced in Radix Polygoni
      Multiflori after processing].
AB  - OBJECTIVE: To analysis the changes of two chemical constituents, namely 2, 3
      dihydro-3, 5- dihydroxy-6-methyl-4H-pyran-4-one (DDMP) and 5-hydryoxymethyl
      furfural (5-HMF) produced in Radix Polygoni Multiflori after processing, with
      processing time, and to determine the contents of 5-HMF in samples of Radix
      Polygoni Multiflori and Radix Polygoni Multiflori preparata. METHOD: An HPLC
      method was applied with a Zobax SB-C18 (3.9 mm x 150 mm, 5 microm) column by a
      elution using methanol-water (10: 90) as the mobile phase. The detection was set
      at UV 280 nm. RESULT: The contents of DDMP were increasing with the processing
      time until 24 hour, followed by a decrease until 60 hour process. The contents of
      5-HMF were increasing gradually throughout the 60 hour steaming process. The
      contents of 5-HMF in 11 samples of Radix Polygoni Multiflori preparata were from
      0.013% to 0.101%, and only one in 4 samples of Radix Polygoni Multiflori
      containing trace amount of 5-HMF. CONCLUSION: The chemical components in Radix
      Polygoni Multiflori were changed during the processing procedures. Therefore, the
      processing of Radix Polygoni Multiflori should be controlled and standardized.

PMID- 19157119
TI  - [Simultaneous determination of four components in Hedyotis diffusa oral solution
      by reversed-phase HPLC].
AB  - OBJECTIVE: A new method for simultaneous determination of four methyl-3, 4
      dihydroxybenzoate ( I ), P-coumaric acid (II), ferulaic acid (III) and E-6-O-P
      coumaroyl scandoside methyl ester (IV) in Hedyotis diffusa oral solution by
      reversed-phase HPLC was developed. METHOD: The separation was performed on a
      Diamonsil C18 column (4.6 mm x 250 mm, 5 microm) with gradient elution. A
      acetonitrile, B-methonal-water-glacial acetic acid (5: 95: 0.25), 0-20 min, 1% 
      16% A; 2042 min, 16% A; 42-46 min, 16%-20%A; 46-65 min, 20% A. The UV detection
      was set at 265 nm; flow rate 1.0 mL x min(-1). RESULT: There was good linearity
      between the peak area and concentration at the ranges of 2.1-105 (r = 0.999 8),
      3.5-175 (r = 0.999 8), 1.72-86 (r = 0.999 9), 4.0-200 mg x L(-1) (r = 1.000 0)
      for I, II, III and IV respectively. The average recoveries of I, II, III and IV
      were 99.9%, 97.9%, 98.6% and 98.1%. CONCLUSION: The method is rapid, simple and
      accurate, and it can be used for the evaluation of H. diffusa oral solution.

PMID- 19157120
TI  - [Optimal extraction of nuciferine and flavone from lotus leaf based on central
      composite design and response surface methodology].
AB  - OBJECTIVE: To optimize the process of extracting effective constituents from
      lotus leaf. METHOD: Independent variables were ethanol concentration reflux time
      and solvent fold, dependent variables were extraction rates of nuciferine and
      flavone in lotus leaf, central composite design and response surface methodology
      were used for optimization of extraction of lotus leaf. RESULT: The optimum
      conditions of extraction process were 75% -80% ethanol, 2-3 hours for reflux, 20
      25 fold solvent and 2 times for extraction. Bias between observed and predicted
      of rates of nuciferine and flavone values were 5.53%, -6.02%, respectively.
      CONCLUSION: The values observed and predicted were close to each other, which
      proved that the optimization of of extraction of lotus leaf by central composite
      design and response surface methodology was reasonable and successful.

PMID- 19157121
TI  - [Optimal technique of wine-processed gentian].
AB  - OBJECTIVE: To optimize technique of wine-processed gentian (root of Gentiana
      manshurica, G. scabra, G. triflora and G. rigescens. METHOD: Orthogonal design L9
      (3(4)) was used to select the best processing technical parameters by yields of
      the water extracts and amounts of gentiopicroside in the processing products.
      RESULT: The optimal procedure was suggested as follows: Gentiana Radix was cut
      into 5-10 millimetres' long, added one-fifth amounts of wine by gentian's weight,
      moistened for two hours, and then dried by slow fire. CONCLUSION: The amounts of
      gentiopicroside in wine-processed gentian were closely related to the types and
      amounts of wine, moistened time and dried method.

PMID- 19157122
TI  - [Preparation of coated tablets of glycyrrhetic acid-HP-beta-cyclodextrin tablets
      for colon-specific release].
AB  - OBJECTIVE: To prepare coated tablets of glycyrrhetinic acid and hydroxypropyl
      beta-cyclodextrin (GTA-HP-beta-CYD) inclusion complex tablets for colon-specific
      release. METHOD: In order to improve the solubility of GTA, the GTA-HP-beta-CYD
      inclusion complex was prepared by ultrasonic-lyophilization technique and its
      formation were characterized by X-ray powder diffraction profiles and infrared
      spectrometry. The effects of inclusion condition on the inclusion efficiency and
      stability coefficient of inclusion complex were investigated, respectively. After
      prepared GTA-HP-beta-CYD tablets by powder direct compression, the pH dependant
      polymer Eudragit III and/or mixed with Eudragit II were used for further coating
      materials in fluid-bed coater. The influences of coating weight on the GTA
      release in different pH conditions were evaluated to establish the method for
      prepering colon specific delivery tablets with pulsed release properties. RESULT:
      The formation of inclusion complexes were proved by X-ray powder diffraction
      profile and phase solubility curve. The effect of pH value of solvent was played
      critical role on the preparation of GTA- HP-beta-CYD inclusion complex. And the
      inclusion efficiency of GTA was 9. 3% and the solubility was increased to 54. 6
      times at optimized method. The Eudragit III coated GTA- HP-beta-CYD tablets with
      coating weight 10% and 16% were showed pH dependant colon specific release
      profiles with slow release rate. The release profile of tablets coated with the
      mixture of Eudragit II and Eudragit III (1:2) were indicated typical pH dependant
      colon specific and pulsed release properties while the coating weight was 17%.
      CONCLUSION: The preliminary method for preparation of colon specific release
      tablets containing glycyrrhetinic acid with improved solubility was established
      for further in vivo therapeutic experiment.

PMID- 19157123
TI  - [Studies on quality standard of PsL 5F injections].
AB  - OBJECTIVE: To establish the quality standard of PsL injections containing mainly
      5F (ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid). METHOD: The
      identification of PsL was performed by thin-layer chromatography, and the content
      was determined by HPLC. The column was Hypersil C18 (4.6 mm x 250 mm, 5 microm),
      the mobile phase was the mixture of methane-water-acitic acid (55:45: 0.045) with
      a flow rate of 1.0 mL x min(-1), the detective wavelength was 254 nm, and the
      column temperature was maintained at 35 degrees C. The pH value and K+ content of
      the three batchs injection were determined with pH meter and flame photometric
      meter, and the contents of tannin, protein, oxalic acid salt and heavy metals
      were detected by deferent methods. RESULT: The TLC method was suitable for the
      identification of PsL5F. The linearity for 5F was obtained over the range of 30
      240 microg x mL(-1) (r = 0.999 8), the average recovery of 5F was 99.8%. The
      injections were of pH value range from 7.80 to 8.20, K+ contents less than 10
      mmol x L(-1), and the contents of tannin, protein, oxalic acid salt and heavy
      metals were qualified with the Chinese pharmacopoeia, respectively. CONCLUSION:
      It's sensitive and reliable that can be used as quality control methods of PsL5F
      injections.

PMID- 19157124
TI  - [Chemical constituents in aerial part of Reineckea carnea].
AB  - OBJECTIVE: To study the chemical constituents in the aerial part of Reineckea
      carnea. METHOD: The compounds were isolated by extraction, silica gel, gel, and
      reversed-phase silica gel coloum chromatography, and high-performance liquid
      chromatography. The structures were identified by various spectroscopic methods
      including 1D and 2D NMR spectrum, MS, IR, etc. RESULT: Six compounds were
      isolated and identified as 1alpha, 3beta-dihydroxy-5beta-pregn-16-en-20-one-3-O
      beta-D-glucopyranoside (1), syringaresinol-beta-D-glucoside (2), sophoraflavone B
      (3), stigmast-5, 22-dien-3-O-beta-D-glucopyranoside (4), daucosterol (5), a-D
      glucose (6). CONCLUSION: Compound 1 was a new compound, coumpounds 2-6 were
      obtained from the plant for the first time.

PMID- 19157125
TI  - [Chemical constituents from barks of Garcinia tetralata].
AB  - OBJECTIVE: To study the chemical constituents of the barks of Garcinia tetralata.
      METHOD: Compounds were isolated and purified repeatedly by silica gel and ODS
      column chromatography and their chemical structures were elucidated by their
      physicochemical properties and spectral data analysis. RESULT: Ten compounds were
      obtained and identified as 1, 7-dihydroxyxanthone (1), buchanaxanthone (2),
      garciniaxanthone H (3), 1, 2, 5-trihydroxyxanthone (4), subelliptenone H (5), 6
      desoxyjacareubin (6), 6-deoxyisojacreubin (7), subelliptenone G (8), methyl
      orsellinate (9) and beta-sitosterol (10). CONCLUSION: Compounds 1-10 were
      isolated from this plant and compound 9 was obtained from the genus Garcinia for
      the first time.

PMID- 19157126
TI  - [Studies on chemical constituents of root tuber of cultivated Pseudostellaria
      heterophylla (Zheshen No. 1)].
AB  - OBJECTIVE: To study the chemical constituents of the cultivated Pseudostellaria
      heterophylla (Zheshen No. 1) as a traditional Chinese medicine, and provide a
      scientific basis for its quality evaluation. METHOD: The chemical constituents
      were isolated by silica gel column chromatography and structurally elucidated by
      analysis of their physicochemical characteristics including spectroscopic data.
      RESULT: Thirteen compounds were obtained and identified as taraxeryl acetate (1),
      taraxerol (2), stigmast-7-en-3beta-ol(3), beta-sitosterol (4), daucosterol (5),
      stigmast-7-en-3-O-beta-D-glucopyranoside (6), dihydroferulic acid [3-(4-hydroxy-3
      methoxyphenyl) propionic acid] (7), adenosine (8), uridine (9), alpha-ethyl-D
      galactopyranoside (10), 3-furfuryl pyrole-2-carboxylate (11), glucose (12), and
      sucrose (13), respectively. CONCLUSION: Compounds 1, 2 and 7-10 were isolated
      from the root tuber of P. heterophylla for the first time.

PMID- 19157127
TI  - [Saponins from roots of Stephanotis mucronata].
AB  - OBJECTIVE: To study the chemical constituents from n-BuOH fraction of the roots
      of Stephanotis mucronata. METHOD: The compounds were separated by chromatographic
      methods. A combination of UV, MS, and NMR spectroscopic methods was applied to
      identify structure of these compounds. RESULT: Four oleane saponins were isolated
      and identified as sitakisoside VII (1), sitakisoside VI (2), sitakisoside II (3),
      and sitakisoside I (4). CONCLUSION: These four compounds were obtained for the
      first time from this plant.

PMID- 19157128
TI  - [Study of GC fingerprint of essential oils from flower of Lonicera japonica].
AB  - OBJECTIVE: To study and establish the GC fingerprint of essential oils of 10
      batches the flower of Lonicera japonica. METHOD: The essential oils were
      extracted by steam distillation from ten batches of the flowers, then separated
      by capillary gas chromatography. RESULT: The similarity of 10 batches of the
      flower of L. japonica was high. CONCLUSION: The method was reliable, and can be
      used to evaluate the quality of the flower of L. japonica.

PMID- 19157129
TI  - [Study on fingerprints of Citrus aurantium from different places by capillary
      electrophoresis].
AB  - OBJECTIVE: To develop a high performance capillary electrophoresis method for
      Citrus aurantium fingerprints to control its quality. METHOD: The background
      electrolyte (BGE) was an 80 mmol x L(-1) boric acid solution containing 15 mmol x
      L(-1) borate. The pH of the BGE was adjusted to 9.70 with KOH solution. The
      detection wavelength was 201 nm and a voltage of 16 kV was applied. The sample
      hydrodynamic injection was 0.4 ps with a duration time of 8 sec. C. aurantium was
      extracted by water and a set of capillary electrophoresis fingerprints (CEFP)
      containing 12 co-possessing peaks was obtained. RESULT: There were good
      similarities between the standard CEFP and each set of CEFP of C. aurantium
      collected from eleven different places, and their similarity coefficients were
      between 0.973 and 0.996. CONCLUSION: The CEFP has acceptable precision,
      reproducibility and stability and can be used for the quality control of C.
      aurantium.

PMID- 19157130
TI  - [Effect of vinblastine nanoparticles on antiproliferation in human glioma cell
      lines BT325].
AB  - OBJECTIVE: To compare antiproliferation effects of vinblastine nanopraticles and
      vinblastine water solution in human glioma cell lines BT325. METHOD: Vinblastine
      nanoparticles were prepared by emulsion polymerization process and using dextran
      as a stabilizing agent. It was characterized by means of morphology, size, drug
      entrapment efficiency and loading efficiency. Human glioma cell lines BT325 were
      treated with different concentrations of vinblastine nanoparticles and
      vinblastine water solution for 48 h, Antiproliferation effect was measured by MTT
      method. Morphological changes were observed by inverted microscope, transmission
      electron microscope and scanning electron microscope. RESULT: Mean diameter of
      VLB-PBCA-NP was about 74.4 nm, and drug entrapment efficiency and loading
      efficiency was 78.47% and 39.24%, respectively. Cell growth inhibition rate of
      vinblastine nanoparticles group and vinblastine water solution group in a
      concentration range (5-5 000 g x L(-1)) for 48 h was 41%, 49%, 73%, 83% and 28%,
      33%, 54%, 60% respectively. Entrapment of VLB in NPS may distinctly degrade
      absorbency as compared to free drugs. Glioma cell BT325 which treated with VLB
      water solution were initial stage of apoptosis, and apoptosis body were forming.
      But VLB NPS-treated BT325 cells were intermediate or end stage, and missed
      structure integrality. CONCLUSION: VLB-PBCA-NP and VLB water solution could
      inhibit the growth of human glioma cell lines BT325, and VLB nanoparticles have
      stronger inhibition effect compared with VLB water solution in the same dose.
      PBCA may be effective as promising carrier for the transport of vinblastine into
      the glioma cells.

PMID- 19157131
TI  - [Determination of paeoniflorin in rat plasma by HPLC-MS/MS and its
      pharmacokinetics].
AB  - OBJECTIVE: An HPLC-MS/MS assay was established to determine paeoniflorin in rat
      plasma and be used to investigate the effect of pharmacokinetics of paeoniflorin
      when co-administrated Radix Angelicae Sinensis and Radix Paeoniae Rubra. METHOD:
      HPLC-MS/MS was performed in the multiple reaction monitoring (MRM) mode using
      target ions at m/z 450 --> m/z 327 for paeoniflorin and m/z 388 --> m/z 225 for
      jasminoidin. A single dose of Radix Paeoniae Rubra alone and with Radix Angelicae
      Sinensis was given to rats by ig, the dosage of paeoniflorin was 294.78 mg x kg(
      1). Concentrations of paeoniflorin in rat plasma were determined by HPLC-MS/MS
      assay and main pharmacokinetic parameters were estimated. RESULT: The mainly
      pharmacokinetic parameters of paeoniflorin when administrated Radix Paeoniae
      Rubra only were as follows: C(max) (1.55 +/- 0.53) mg x L(-1), T(max) (0.9 +/-
      0.3) h, t 1/2 (1.51 +/- 0.63) h, MRT (3.08 +/- 0.74) h, AUC(0 --> tau) (4.68 +/-
      0.85) mg x h(-1) x L(-1). When the two drugs administrated together, the
      corresponding parameters were (0.93 +/- 0.42) mg x L(-1), (1.5 +/- 0.8) h, (3.08
      +/- 1.79) h, (5.19 +/- 1.95) h, (3.36 +/- 0.56) mg x h(-1) x L(-1), respectively.
      The parameters of C(max), AUC(0 --> tau) and MRT were significantly changed (P <
      0.05). CONCLUSION: Radix Angelicae Sinensis can significantly affect the
      pharmacokinetics of paeoniflorin, the principal component of Radix Paeoniae
      Rubra.

PMID- 19157132
TI  - [Studies on predict of absorption of corynanthine, yohimbine, ajmalicine and
      ajmaline across human intestinal epithelial by using human Caco-2 cells
      monolayers].
AB  - OBJECTIVE: To predict the absorption of corynanthine (COR), yohimbine (YOH),
      ajmalicine (AMC) and ajmaline (AML) as chemical constituents of some traditional
      Chinese medicines in human intestinal epithelial. METHOD: By using Caco-2 (the
      human colonic adenocarcinoma cell lines) cell monolayers as a human intestinal
      epithelial cell model, the permeability of COR, YOH, AMC and AML were studied
      from apical side (AP side) to basolateral side (BL side) or from BL side to AP
      side. The four alkaloids were measured by high performance liquid chromatography
      (HPLC) coupled with UV detector. Transport parameters and apty) and atenolol (a
      control substance of poor permeability). The relationship between P(app) and log
      D values of four alkaloids was investigated by using drugs ADMET predict
      software. RESULT: The P(app) values of COR, YOH, AMC and AML were (1.863 +/-
      0.055) x 10(-5), (1.540 +/- 0.082) x 10(-5), (2.522 +/- 0.246) x 10(-5) and
      (1.155 +/- 0.099) x 10(-5) cm x s(-1) from AP side to BL side, and (2.390 +/-
      0.017) x 10(-5), (1.987 +/- 0.154) x 10(-5), (1.374 +/- 0.260) x 10(-5) and
      (2.418 +/- 0.124) x 10(-5) cm x s(-1) from BL side to AP side, respectively,
      which P(app) values were identical with that of propranolol [(2.23 +/- 0.10) x
      10(-5) cm x s(-1) from AP to BL side]. The ratio of P(app B --> A)/P(app A -->B)
      of COR, YOH, AMC and AML were 1.28, 1.29, 0.54 and 2.09, respectively, which
      suggested that the efflux transport of AML was 2.09 times higher more than its
      influx transport. CONCLUSION: COR, YOH, AMC and AML can be transported and
      absorbed across the human Caco-2 cells monolayers, and they belong to completely
      absorbed compounds. AML may have been involved in efflux mechanism in Caco-2
      cells monolayers model from the BL to AP side direction. The oil-water partition
      coefficient play key roles in the transport and absorption of the four alkaloids.

PMID- 19157133
TI  - [Phenolic acids from Arnebia euchroma mifepristone in anti-early pregnancy of SD
      rattus norvegicus].
AB  - OBJECTIVE: Observing the effect of phenolic acids from Arnebia euchroma assist
      mifepristone in anti-early pregnancy of SD rattus norvegicus. METHOD: Feed the SD
      rattus norvegicus with phenolic acids from A. euchroma during the 7 th to 9 th
      day, and then we observe the restaining rate of pregnancy. At the same time, we
      determine the progesterone level in blood serum in the ways of radioimmunoassay.
      RESULT: 720 g x kg(-1) enolic aids from A. euchroma can markedly increase the
      restaining rate of pregnancy (P < 0.05) than that only mifepristone dose (8.0 g x
      kg(-1)). In addition, the number of everage still bith increase, however, to the
      pogesterone level in blood serum. It has little effect. CONCLUSION: The effect of
      phenolic acids from A. euchroma assist mifepristone in anti-early pregnancy of SD
      rattus norvegicus is clear, and it dosen't work in the ways of decreasing the
      pogesterone level.

PMID- 19157134
TI  - [Influence of Qianlie Antong tablets on expresstion of VEGF and bFGF in protatic
      tissues of BHP rats].
AB  - OBJECTIVE: To evaluate the effect of Qianlie Antong tablet (QLAT) on the tissues
      of benign prostatic hyperplasia (BPH) of experimental rats, and seek its
      mechanism. METHOD: The animal model of BPH was made with rats by subcutaneously
      injecting methylacetic acid testosterone after emasculated. The changes of
      prostatic tissues of every group are studied with morphometry combining the
      immunohistochemistry method, the expression of vascular endothelial growth factor
      (VEGF) and basic fibroblast growth factor (bFGF) in prostate tissue were examine.
      RESULT: QLAT can diminish the gland weight, volume and index of prostate,
      compared with control group, and also can decrease average area and circumference
      of gland, and increase the amount of total glands in equal area. Meanwhile, the
      expression of bFGF and VEGF in prostatic tissues were decreased in GANT groups,
      compared with control group. CONCLUSION: QLAT can diminish the prostate gland
      volume, which may be attained by inhibiting the expression of VEGF and bFGF in
      prostatic tissue.

PMID- 19157135
TI  - [Effects of total glucosides of paeony on enhancing insulin sensitivity and
      antagonizing nonalcoholic fatty liver in rats].
AB  - OBJECTIVE: To study the pathological changes of blood glucose, serum lipid,
      insulin resistance, liver function, liver cell denaturalization of total
      glucosides of paeony on nonalcoholic fatty liver rats caused by insulin
      resistance and discuss the acting mechanism. METHOD: Adult SD rats were
      maintained on high-fat-sugar-salt diet for 56 days. In the 57th day, their
      fasting blood glucose (FBG) and 2-hours blood glucose after oral glucose
      tolerance test (OGTT-2 hBG) were mensurated, according to which and the weight
      the rats were divided randomly into nonalcoholic fatty liver model group,
      metformin group (0.2 g x kg(-1)) and total glucosides of paeony group (high
      dosage 0.15 g x kg(-1), low dosage 0.05 g x kg(-1)). All the rats were still
      administered the same diet and given different drugs by intragastric
      administration for 28 days. In the 29th day, all of them were killed and the
      blood was sampled to measure the levels of blood glucose [FBG, OGTT-2 hBG,
      fasting insulin (Fins)] and serum lipid [free fatty acids (FFA), triglyceride
      (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and
      high-density lipoprotein cholesterol (HDL-C)], then the HOMA insulin resistance
      index (HOMA-IRI, fasting glucosexinsulin) and insulin sensitivity index (ISI)
      were counted. The activities of aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), cholinesterase (ChE), superoxide dismutase (SOD) and the
      contents of malondialdehyde (MDA) were measured also. Livers were weighed and
      collected to be observed the pathological changes. RESULT: Compared with normal
      group, in nonalcoholic fatty liver model group the levels of Fins and IRI were
      increased obviously (P < 0.01), ISI were decreased (P < 0.01), FFA, TG, TC, LDL-C
      were increased (P < 0.01), HDL-C were decreased (P < 0.05); the content of MDA
      were increased (P < 0.05), the activities of SOD were decreased (P < 0.01); AST,
      ALT and ChE were increased (P < 0.05, or P < 0.01), the pathological changes of
      liver fat were severe (P < 0.01). In glucosides of paeony group and metformin
      group, hyperinsulinaemia and insulin resistence were resisted (P < 0.05, or P <
      0.01); the levels of FFA, TG, TC, LDL-C were decreased and HDL-C were increased
      (P < 0.05, or P < 0.01); the activities of AST, ALT, ChE were decreased (P <
      0.05, or P < 0.01) and SOD were increased (P < 0.01). The contents of MDA were
      decreased (P < 0.05). The levels of FBG and 2 hBG in metformin group were
      decreased but in total glucosides of paeony group were not decreased obviously.
      CONCLUSION: Total glucosides of paeony may protect liver function and modulate
      serum lipid for the fatty liver rats caused by insulin resistance, and its action
      mechanism may be concerned with enhancing insulin sensitivity and antioxidative
      ability, decreasing serum lipid.

PMID- 19157136
TI  - [Effect of oxymatrine on NF-kappaB and other cell factors in rats lung tissue
      with septic shock].
AB  - OBJECTIVE: To explore the effects of oxymatrine (OMT) on NF-kappaB and other cell
      factors in rat lung tissue with septic shock. METHOD: Fifty-six male SD rats were
      randomly divided into 7 groups: sham operation group, OMT control group, model
      (CLP) group, CLP + OMT high, middle, low-dose group, positive control group.
      Changes in NF-kappaB (p65) and IkB-alpha activity in the pulmonary tissue were
      determined by immunohistochemical method, tumour necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6) levels in pulmonary tissue were determined by
      radioimmunoassay. RESULT: OMT could decrease significantly the NF-kappaB (p65)
      and IkB-alpha activity in the pulmonary tissue (P < 0.05), TNF-alpha and IL-6
      levels in pulmonary tissue homogenate decreased markedly (P < 0.05). OMT could
      elevate the content of PaO2, SaO2, decrease the content of PaCO2, HCO3- and
      decrease the ratio between wet weight of the lung and dry weight of the lung and
      the PWI. CONCLUSION: OMT can inhibit NF-kappaB-inducing kinase (NIK), NF-kappaB
      activity and reduce the expression of proinflammatory factor (TNF-alpha, IL-6)
      and antagonize the lung injury in a rat model of septic shock.

PMID- 19157137
TI  - [Studies and reports of Chinese cut crude drugs dosage in clinical prescription
      of traditional Chinese medicine (section of pediatrics)].
AB  - OBJECTIVE: Study the actual dosage of clinical prescription in pediatrics of
      traditional Chinese medicine (TCM), and offer the consummate data for formulating
      the dosage standard of Chinese cut crude drug. METHOD: We made use of the methods
      of stratified sampling and random sampling to investigate 38 736 broth
      prescriptions of pediatrics of TCM in 21 various hospitals, 18 provinces, and
      constructed the database, then applied Weka KDD software to analyze. RESULT: We
      identified the frequency and clinical dosage intervals of 300 drugs, and the
      practical dosage of 155 drugs. Most of drug's dosage centralized the four
      intervals: (3-6], (6-9], (9-12], (12-15], and the concrete dosage were 6, 9, 10,
      12, 15 g, etc. CONCLUSION: The dosages in the pharmacopoeia are not coincided
      with the practical dosages in pediatrics, and demand to revise. This paper will
      offer the consummate data for formulating the new dosage standard.

PMID- 19157138
TI  - [Clinical analysis of hepatic veno-occlusive disease induced by Sedum aizoon].
AB  - OBJECTIVE: To discuss the clinical characteristics and precautionary measures of
      hepatic veno-occlusive disease (VOD) caused by Sedum aizoon. METHOD: The VOD
      induced by Sedum aizoon were reports in 41 patients comimg from national medical
      journals from 1998 to 2007 and their use and dose were analyzed. RESULT: The
      results shows that ADR of Sedum aizoon was serious. VOD has relationship with it,
      s dose use time the age of the patients and individual difference. CONCLUSION: To
      avoid of VOD induced by Sedum aizoon, it should be done through strengthening
      study on pharmacology and toxicology of Sedum aizoon. Enhancing patients of
      safety awareness, standardizing usage and dosage to guide the clinically rational
      use of drugs.

PMID- 19157139
TI  - [Clinical curative effect of combination between medicine and acupoint flow on
      SOD, NO in patients with ulcerative colitis].
AB  - OBJECTIVE: To investigate the clinical curative effect of the combination between
      medicine and acupoint flow on SOD, NO in patients with ulcerative colitis.
      METHOD: Two hundred sixty two patients with ulcerative colitis were randomly
      divided into four groups: the patients in traditional Chinese medicine group were
      fed with changpikang, the patients in ear acupoint group were pasted and pressed
      spleen, large intestine, sympathesis, subcortex; the patients in medicine and
      acupoint group were taken with Changpikang and ear acupoint; the patients in
      treatment group were treated by taking sulfasalazine, with a treatment course of
      four weeks. The changes of SOD, NO before and after treatments were recored.
      RESULT: There was a significant difference between four groups before and after
      treatment (P < 0.05), medicine and acupoint group was superior to that others (P
      < 0.05). CONCLUSION: The method of combination between medicine and acupoint
      could increase the contents of SOD, decrease the level of NO, elevate the
      potential of organism to resist oxygen free radical and promote intestinal tract
      ulcer concrescence.

PMID- 19157140
TI  - [Explore pros and cons of proproetary Chinese medicines and Western medicines].
AB  - Improve the Medication methods and the efficacy of Chinese medicines with western
      medicines. Read the according article, compare the advantage and disadvantge of
      Chinese medicines and western medicines interaction and describe the mechanism of
      medicines in effect. It shows that using Chinese medicines with western medicines
      have more disadvantage than adavntage. The clinical Chinese medicines with
      western medicines should according physical properties and pharmacological
      effects of drug at first, after taking, general the interval is from 1 hour to 3
      hours to prevent medicine has physical reactions or toxicity in stomach, ensure
      taking medicines safety.

PMID- 19157141
TI  - [Review about structure-function relationships of anthraquinone derivatives from
      Radix et Rhizoma Rhei].
AB  - It review the structure-function relationship of natural anthraquinone
      derivatives from Radix et Rhizoma Rhei. The anthraquinone derivatives had many
      identical activities because they have the identical mother nucleus; but the
      strength of their activities were different, because they have different
      substitution groups. The anthraquinone derivatives shown the obvious structure
      function relationship in many respects, such as antioxygenation, antibiosis,
      anticancer, the influence of immunity and so on.

PMID- 19157142
TI  - [The expression and significance of urokinase-type plasminogen activator and its
      receptor in squamous cell carcinoma of hypopharynx].
AB  - OBJECTIVE: To investigate the expression of urokinase-type plasminogen activator
      (uPA) and its receptor (uPAR) in squamous cell carcinoma of hypopharynx and
      reveal the correlation of the major clinicopathological parameters and prognosis.
      METHOD: Samples of 48 hypopharyngeal carcinoma and 10 normal hypopharyngeal
      tissue were detected by immunohistochemistry method (SP method) for urokinase
      type plasminogen activator (uPA) and its receptor (uPAR). The correlation between
      the expression of urokinase-type plasminogen activator and its receptor and the
      major clinicopathological parameters of hypopharyngeal carcinoma were analyzed by
      rank sum test and Spearman correlation analysis. Overall survival were analyzed
      according to Kaplan-Meier and log-rank statistics, the prognostic relevance of
      uPA and uPAR and conventional prognostic factors were analyzed by Cox analysis.
      RESULT: In 48 hypopharyngeal carcinoma specimens, positive expression rates of
      uPA and uPAR were 77.1% and 68.75% respectively, which were significantly higher
      than in normal tissues (P < 0.01). The uPA and uPAR positive expression was
      correlated with pathological grading, lymph node metastases and growth mode of
      hypopharyngeal carcinoma. The positive expression rate for uPA and uPAR in
      patients with lower pathological grading, lymph node metastases and invasion
      growth mode were significantly higher than in patients with higher pathological
      grading, non-lymph node metastases and non-invasion growth mode. Patients were
      followed-up postoperatively. The positive expression of uPA and uPAR were
      correlated with prognosis (P < 0.05 and P < 0.01). According to Log-rank
      statistics, patients with positive expression of uPA and uPAR had a significantly
      shorter survival time than those with negative expression of uPA and uPAR.
      Multivariate Cox analysis revealed that three independent prognostic factors for
      overall survival time were clinical stage, invasion growth mode and uPAR
      expression. CONCLUSION: The positive expression of uPA and uPAR in hypopharyngeal
      carcinoma were significantly higher than in normal tissues. uPAR is a new
      independent and strong biologically prognostic factors, which positive expression
      may be a powerful aid in evaluating metastatic potential and High-Risk patients
      in early stage of hypopharynx carcinoma ryngeal carcinoma.

PMID- 19157143
TI  - [The application of micro-suture technology in laryngeal microsurgery].
AB  - OBJECTIVE: To explore the effect of micro-suture technology in laryngeal surgery.
      METHOD: Sixty-one patients with benign laryngeal disease underwent microsurgery
      resection under general anesthesia, and the wound surface of the mucosa was
      sutured intermittently. RESULT: The postoperative healing time was shortened, the
      cicatrix on the vocal cord mucosa was reduced, the voice quality was improved
      significantly and the recurrence rate was reduced. CONCLUSION: The micro-suture
      technology is effective in improving the voice quality and surgery effect
      significantly.

PMID- 19157144
TI  - [Apoptosis of laryngeal carcinoma cells induced by antisense
      oligodeoxynucleotides complementary Stat3 in vitro].
AB  - OBJECTIVE: To study the effects of oligodeoxynucleotides complementary Stat3 on
      apoptosis in laryngeal carcinoma Hep-2 cell. METHOD: Oligodeoxynucleotides
      complementary Stat3 was designed, which was transferred into laryngeal carcinoma
      Hep-2 cell by lipofection. Expression of Stat3 and p-Stat3 were detected by
      Western blot and PCR. MTT was used to observe the growth-inhibiting ratio. DNA
      ladder, AO/EB and FCM were used to observe the apoptosis of laryngeal carcinoma
      cell Hep-2 in vitro. RESULT: Western blot and PCR results demonstrated that
      oligodeoxynucleotides complementary Stat3 could significantly inhibit the
      expression of Stat3 and p-Stat3 in Hep-2 cell. MTT results showed that it could
      significantly suppress the growth of Hep-2 cell. The DNA ladder, AO/EB and FCM
      results showed it could inhibit the expression of Stat3 and induce the apoptosis
      of Hep-2 cell in a concentration-dependent manner. CONCLUSION:
      Oligodeoxynucleotides complementary Stat3 could induce the apoptosis and suppress
      cell proliferation in laryngeal carcinoma Hep-2 cell.

PMID- 19157145
TI  - [The relationship between spontaneous apoptosis and radiation-induced apoptosis
      of laryngeal carcinoma].
AB  - OBJECTIVE: To study the change of laryngeal carcinoma cell apoptosis before and
      after radiotherapy. METHOD: Living tissue of diseased region obtained from 27
      cases of laryngeal carcinoma before and during radiotherapy 10, 30 and 60 Gy were
      used in this study. With terminal deoxynucleotidyl transferase mediated dUTP
      biotin nick end labeling (TUNEL), the spontaneous and radiation-induced apoptotic
      rate (AR)were examined. RESULT: The AR of living tissue of laryngeal carcinoma
      before and during radiotherapy 10, 30 and 60 Gy were (21.0 +/- 0.7)%, (60.0 +/-
      1.5)%, (42.0 +/- 1.3)%, (25.0 +/- 1.9)%, respectively. The radiation-induced
      apoptotic rate was significantly higher than that of spontaneous apoptotic rate
      (P< 0 . 5). In laryngeal carcinoma, spontaneous apoptosis was positively
      correlated with the radiation-induced apoptosis. CONCLUSION: Detecting of AR of
      laryngeal carcinoma cells before and during radiotherapy may be helpful to
      predict the sensitivity of radiotherapy in laryngeal carcinoma patients.

PMID- 19157146
TI  - [Auditory brainstem response testing revisit of infants who failed the hearing
      screening].
AB  - OBJECTIVE: Analyze the ABR testing results of local infants who failed the
      hearing screening and summarize its characteristics. METHOD: Carry on the first
      ABR test to 140 infants who failed the newborns' hearing screening when they are
      about 3-month age, the unusualities carry on the second ABR test at about 6-month
      age, and carry on the statistical analysis. RESULT: One hundred and forty infants
      with the first ABR diagnosis, 65 infants are normal, accounting for 46.43%; 75
      infants have single or binaural ear hearing disorder, accounting for 53.57%,
      single ear 17.14%, binaural ear 36.43%, of which mild hearing disorder takes
      most, accounting for 27.14%, the profound hearing loss is also not extremely
      rare, accounting for 14.29%. Between male and female hearing disorder disease
      incidence rate difference is not remarkable statistics significance (P > 0.05).
      Between the number of high-risk in the hearing injury and non-high-risk after the
      comparison difference is not remarkable statistical significance (P > 0.05). With
      the population of above severe loss in hearing high-risk has the remarkable
      statistical significance with the non-high-risk comparison difference (P < 0.05).
      The second ABR subsequently visit 38 infants, 8 infants normal, total normal rate
      52.14% (73/140), 16 infants mild hearing disorder 10 infants transfer normal
      either the change for the better, 6 infants do not have the change or the
      aggravation, 3 infants moderate hearing disorder 1 infant changes for the better,
      2 infants do not have the change, 9 infants severe hearing disorder 3 infants
      have the change for the better, 3 infants do not have the change, 3 infants
      aggravate, 10 infants profound hearing disorder 9 infants do not have the change
      or the aggravation extremely, 1 example brain paralysis profound hearing disorder
      extension converges normally extremely. The non-high-risk whose hearing changes
      for the better is obviously higher than high-risk (P < 0.05). CONCLUSION: Should
      develop newborns' hearing screening comprehensively with key attention to high
      risk loss of hearing. The severe hearing disorder has the variability, and so on
      exceptional child hearing situation appraisal should be prudent to the brain
      paralysis; should establish perfect tracing, revisiting and managing system as
      soon as possible.

PMID- 19157147
TI  - [Reconstruction of laryngotracheal stenosis with hyoid graft and pedicle
      sternohyoid muscle flaps].
AB  - OBJECTIVE: To evaluate the possibility and reliability of hyoid graft and pedicle
      sternohyoid muscle flaps in the reconstruction of laryngotracheal stenosis.
      METHOD: Using the single or double pedicle sternohyoid muscle flaps and hyoid
      graft, we repaired laryngotracheal stenosis. RESULT: In all 21 cases with
      laryngotracheal stenosis, 16 cases were cured after one surgical procedure, and 3
      cases were cured after two times of surgical procedures, and 19 cases were
      decannulated, but one case was failure, and one case was lost visiting.
      CONCLUSION: The hyoid sternohyoid graft transfer method was convenient, slightly
      damaging, and had good supporting effects and high survival rate in the
      reconstruction of laryngotracheal stenosis.

PMID- 19157148
TI  - [The expression and potentially clinical significance of heparanase in
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the expression of heparanase in nasopharyngeal
      carcinoma and the relationship between the expression of it and clinically
      pathological features of nasopharyngeal carcinoma. METHOD: The expression of
      heparanase protein in 70 cases of nasopharyngeal carcinomas and 10 cases of
      normal nasopharyngeal tissues was detected by immunohistochemical staining. The
      date of expression combined clinical features, which included clinical stage,
      cervical lymph node metastasis rate, the rate of metastasis and recurrence,
      combination of, the 5-year survival rate, and other analysis, was analyzed.
      RESULT: The positive rate of heparanase protein in cancerous tissues was 52.9%
      (37/70), while it was 0% in normal nasopharyngeal tissues. The positive rates of
      heparanase protein in patients were 30.0% (6/20) in stage I, 45.80% (11/24) in
      stage II, 70.6% (12/17) in stage III, 88.9% (8/9) in stage IV respectively.
      Heparanase positive tumors were associated with a higher incidence of lymph node
      metastasis (67.4%, 31/46) than heparanase negative ones (25.0%, 6/24). The rate
      of distant metastasis and regional recurrence in the heparanase positive group
      was 48.6% (18/37), but only 15.2% (5/ 33) in the heparanase negative group. The
      cumulative survival of patients in the heparanase negative group at 5 years was
      78.8% (26/33), but only 24.3% (9/37) in the heparanase positive group. The
      clinical stage of disease, lymph node metastasis, the rate of distant metastasis
      and regional recurrence of nasopharyngeal carcinoma were correlated with positive
      expression of heparanase protein. CONCLUSION: The expression of HPA was
      associated with invasion and metastasis and prognosis of nasopharyngeal cancer,
      and it may be a new target for the anti-treatment of nasopharyngeal cancer. (P <
      0.01), and heparanase expression level inversely correlated with the patient
      survival (P < 0.01). CONCLUSION: Heparanase may play important roles in the
      invasive infiltration, metastasis, and prognosis in nasopharyngeal carcinoma,
      clearly indicating that heparanase is a possible target for anticancer drug
      development.

PMID- 19157149
TI  - [Clinical analysis on six cases of nonfunctioning parathyroid cysts].
AB  - OBJECTIVE: To study the clinical and pathological characteristics of
      nonfunctioning parathyroid cysts. METHOD: Six cases of nonfunctioning parathyroid
      cysts who were hospitalized during 1997-2007 were retrospectively analyzed. The
      clinical features, serum calcium, B-ultrasonic, CT and nuclide scanning were
      performed. Postoperative pathologic and immunohistochemistry detection in
      nonfunctioning parathyroid cysts were made. RESULT: Tumors in the 6 cases were
      underwent surgical ablation and diagnosis was verified by pathology. CgA
      (chromogranin A), Syn (synaptophysin), NSE (and neuron specific enolase)
      expressions were positive. Follow-up six months and five years after operation,
      there is no recurrence. CONCLUSION: Surgical resection is most effective in
      treating nonfunctioning parathyroid cysts and diagnosis is made by pathologic
      examination.

PMID- 19157150
TI  - [Analysis of characteristics of heart rate and heart rhythm in children with
      obstructive sleep apnea-hypopnea syndrome].
AB  - OBJECTIVE: To investigate the characteristics of heart rate (HR) and heart rhythm
      in children with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHOD:
      Ninety-five patients underwent overnight PSG for clinically suspected OSAHS.
      According to the apnea index (AI), the patients were assigned to control group
      (AI < or = 1/h, SaO2 >92%, n = 27) or OSAHS group (AI > 1/h, SaO2 < 92%, n = 68).
      The HR and heart rhythm were monitored and compared between the two groups.
      RESULT: The maximum HR during sleep was significantly higher in OSAHS group while
      the minimum HR was significantly lower during sleep. Bradycardia and tachycardia
      is a common feature of pediatric OSAHS. There was a significantly higher
      incidence of tachycardia in OSAHS groups than in the control group. CONCLUSION:
      These findings suggest that pediatric OSAHS might influence HR and heart rhythm.

PMID- 19157151
TI  - [Expression of epidermal growth factor receptor Ki67 and p16 in human middle ear
      cholesteatoma].
AB  - OBJECTIVE: This study aimed to analyze the expression of epidermal growth factor
      receptor (EGFR), Ki67 and p16 in human middle ear cholesteatomas and to
      investigate the correlation between its expression and the ability of erosion of
      cholesteatoma. METHOD: The specimens from the acquired middle ear cholesteatoma
      tissue of 30 cases and 21 external ear canal skin samples from patients and 17
      external ear canal skin samples from healthful men were taken intraoperatively.
      Their expression was examined by immunohistochemical SP method. Then we scanned
      it into a computer by an image scanner and quantified the gray of them using
      commercial software. RESULT: The percent of positive expression of EGFR, Ki67 and
      p16 in middle ear cholesteatoma were 70.0%, 60.0%, 46.7%. Their expression tended
      to the increased greatly compared with the skins of the control groups. There was
      not correlation between the expression of EGFR, Ki67 and p16 (P > 0.05). It
      showed statistically significant correlation between expression of EGFR and the
      ability of erosion of middle ear cholesteatoma (P < 0.01). There was correlation
      between the expression of Ki67 and the ability of erosion of middle ear
      cholesteatoma too (P < 0.01). But there was not correlation between the
      expression of p16 and the ability of erosion of middle ear cholesteatoma (P >
      0.05). The expression of EGFR, Ki67, p16 in all epithelial layers of middle ear
      cholesteatoma were abundantly stained, especially in the basal and spinous
      layers. Only the basal layer were slightly stained in control groups. CONCLUSION:
      The expression of EGFR, Ki67, p16 in middle ear cholesteatoma was significantly
      high-er compared with the skin of external auditory of cholesteatoma patients and
      healthful peoples. There was correlation between the expression of EGFR or Ki67
      and the ability of erosion of middle ear cholesteatoma. It means that EGFR, Ki67
      and p16 play a key role in the hyperproliferation middle ear cholesteatoma.

PMID- 19157152
TI  - [Establishment of a cisplatin-induced human nasopharyngeal carcinoma drug
      resistant cell line and its biological characteristics].
AB  - OBJECTIVE: To establish a CDDP-resistant cell line from human nasopharyngeal
      carcinoma and evaluate its biological characteristics. METHOD: By continuously
      exposing and gradually increasing dose of cisplatin (CDDP), a resistant
      nasopharyngeal carcinoma cell line (HNE1/CDDP) was established. Drug sensitivity
      of this cell line was detected by MTT assay; the alterations of its biological
      characteristics were determined using light microscopy, cell counting and flow
      cytometry (FCM); its ability of adhesion, migration and invasion were also
      evaluated. RESULT: HNE1/CDDP cell line was developed after 10 months with stable
      resistance to cisplatin with the resistance index was 5.83. HNE1/CDDP cell
      exhibited cross-resistance to many other chemotherapeutic agents (carboplatin,
      oxaliplatin and etoposide, etc). The morphology of HNE1/CDDP changed; doubling
      time prolonged; and the cell number of S-phase and G2/M-phase decreased while of
      G0/G1 phase increased compared with parental cells. The ability of adhesion,
      migration and invasion had no difference between the parental and the resistant
      cells. CONCLUSION: HNE1/CDDP cell line shows the typical and stable resistant
      phenotype and can be used as a research model.

PMID- 19157153
TI  - [Effect of apoptosis of vesicular stomatitis virus on tumor cells of
      nasopharyngeal carcinoma in vivo].
AB  - OBJECTIVE: To investigate apoptosis induced by vesicular stomatitis virus (VSV)
      in HNE-1 cancer cells of human nasopharyngeal carcinoma by models of nude mice
      BALB/c in vivo. METHOD: HNE-1 cells are collected from culture bottle and
      infected infra right-side post-back epithelium of nude mice-BALB/c (6 x 10(6)
      cells/0.1 ml/each mice) to create HNE-1 tumor models of nude mice-BALB/c. When
      the diameter of HNE-1 tumors is 5 to 8 millimeter, HNE-1 tumor models are treated
      with VSV (1 x 10(8) pfu /ml) or Saline. By Hoechst 33258-staining under
      fluorescence microscope, induction of apoptosis by VSV in HNE-1 tumor models are
      recorded and studied, compared with that by Saline in HNE-1 tumor models in vivo.
      RESULT: Compared with control group of saline, apoptosis of HNE-1 cancer cells of
      human nasopharyngeal carcinoma increase apparently in the remaining tumor cells
      of nude mice treated by VSV (P < 0.01). CONCLUSION: The present study suggests
      that the treatment with VSV could augment the apoptosis cells of human
      nasopharyngeal carcinoma in vivo.

PMID- 19157154
TI  - [Is dissection of levels 4 and 5 justified for cN0 laryngeal and hypopharyngeal
      cancer?].

PMID- 19157155
TI  - Bus drivers' mental conditions and their relation to bus passengers' accidents
      with a focus on the psychological stress concept.
AB  - The purpose of this study was to clarify the psychological factors of bus
      drivers' instability that were related to bus passengers' accidents according to
      the hypothesis model based on the stress concept of Lazarus and Folkman (1984).
      This research was carried out in 2006. Participants of the study were 39 Japanese
      male bus drivers. Their average age was 40.2 (SD: 11.1). The average duration of
      employment was 4.5 (SD:6.1) years. A questionnaire was used that was composed of
      items concerning the frequency of bus passengers' accidents, performance of safe
      driving, job stressors, stress reaction and recognition from others. Based on the
      results, a model assuming that stress reaction caused by job stressors disturbed
      the bus driver's safe driving and was associated with passengers' accidents in
      the bus was verified to some degree. Especially, melancholy and tired feeling
      toward passengers showed a strong relation to the passengers' accidents in the
      bus. This suggested much room for intervention. Moreover, the recognition from
      others of their job was confirmed to act as a control factor of the stress
      reaction.

PMID- 19157156
TI  - The assessment of muscle strain with surface electromyograms during simulated
      mushroom picking.
AB  - Muscle strain was assessed with surface EMG during simulated mushroom picking.
      Nine female subjects performed five periods of work (W1-W5). The duration of each
      period was about 20 min. W1, W2 and W3 were separated by a short break of several
      minutes. W3, W4 and W5 were separated by a rest period of about 43 min. EMGs were
      recorded from the muscles of trapezius, infraspinatus, deltoid and erector spinae
      muscles. Amplitude of EMG (AEMG) and mean power frequency (MPF) of EMG were
      calculated every minute. Ratings of perceived exertion (RPE) were recorded for
      every 5 min. RPE increased during each work period and with the advance of W1-3.
      AEMG increased during some of the work periods in the trapezius and
      infraspinatus. AEMG decreased in a few of the work periods in the other muscles.
      MPF decreased during some of the work periods in the infraspinatus, deltoid and
      erector spinae. The increase of AEMG in the trapezius was interpreted as spare
      capacity for the work. The infraspinatus and deltoid were assessed to be more
      fatigued than the trapezius. The fatigue level of the erector spinae was low.

PMID- 19157157
TI  - Ergonomic intervention for improving work postures during notebook computer
      operation.
AB  - This paper discusses the application of analytical algorithms to determine
      necessary adjustments for operating notebook computers (NBCs) and workstations so
      that NBC users can assume correct work postures during NBC operation. Twenty-two
      NBC users (eleven males and eleven females) were asked to operate their NBCs
      according to their normal work practice. Photographs of their work postures were
      taken and analyzed using the Rapid Upper Limb Assessment (RULA) technique. The
      algorithms were then employed to determine recommended adjustments for their NBCs
      and workstations. After implementing the necessary adjustments, the NBC users
      were then re-seated at their workstations, and photographs of their work postures
      were re-taken, to perform the posture analysis. The results show that the NBC
      users' work postures are improved when their NBCs and workstations are adjusted
      according to the recommendations. The effectiveness of ergonomic intervention is
      verified both visually and objectively.

PMID- 19157158
TI  - Effect of linear polarized near-infrared light irradiation on muscle fatigue
      recovery after repeated handgrip exercise.
AB  - Linear polarized near-infrared light (PL) irradiation is considered one of the
      useful methods for muscle fatigue recovery, because it increases the blood flow
      and skin temperature of the irradiated part. The purpose of this study was to
      examine the effect of PL-irradiation on muscle fatigue recovery and physiological
      response in the upper limbs after maximal repeated rhythmic hand gripping (RRH).
      Ten males and ten females participated in this study. Subjects performed RRH for
      9 min, and then rested for 20 min with PL- or placebo-irradiations. After rest,
      they again performed RRH for 3 min. As evaluation parameters, we selected the
      sustained force curve during RRH, subjective muscle-fatigue sensation (Fs), blood
      lactate concentration (La), muscle oxygenation (Total Hb, Oxy-Hb, and Deoxy-Hb),
      and skin temperature. The decreasing rate of the integrated area for 30 sec
      during RRH was significantly smaller in the PL-irradiation than with the placebo.
      There were no significant differences between irradiation conditions for fatigue
      sensation and lactate concentration skin temperature during rest was kept high by
      PL-irradiation. Muscle oxygenation tended to remain slightly high during the
      initial phase (1-8 min after the exercise). It is inferred that PL-irradiation
      maintains a high skin temperature and blood flow, but it may not contribute to
      recover muscle contraction performance in muscle fatigue.

PMID- 19157159
TI  - Preliminary anthropometric data of medical students for equipment applications.
AB  - Forty-six measurements were measured on 127 medical students (60 males and 67
      females) in Indonesia by using the traditional anthropometric methods. The means,
      standard deviations and, 5th, 50th, and 95th percentile values were calculated
      and presented.

PMID- 19157160
TI  - Why do boys prefer to play with their fathers rather than with their mothers?
AB  - Previous studies carried out in Western countries on mother-infant and father
      infant interactions in play activities revealed the following tendencies. (1)
      Play activities between fathers and their children are physical and unusual,
      whereas, play between mothers and their children are conventional and moderate.
      (2) Boys prefer to play with their fathers, whereas, girls prefer to play with
      their mothers. The previous studies by the author on outdoor play interactions in
      Japanese families suggest that these tendencies may be an adaptation to hunter
      gatherer lives. In the present study, this suggestion was investigated by
      examining whether (1) fathers tend to teach their sons how to fish more
      frequently than they teach their daughters, and (2) boys taught fishing skills by
      their fathers tend to have better fishing skills than other same-aged boys taught
      fishing skills by persons other than their fathers. The experiment was performed
      by obtaining information through a questionnaire from third and fifth grade
      students in four elementary schools. The results indicate the followings. (1)
      Fathers tend to teach their sons fishing more often than they tend to teach their
      daughters. (2) Male students mostly taught fishing by their fathers tend to gain
      better skills in fishing than those mostly taught fishing by persons other than
      their fathers.

PMID- 19157161
TI  - Position paper of the Belgian Working Group on Cardiovascular Prevention and
      Rehabilitation: cardiovascular rehabilitation.

PMID- 19157162
TI  - Statin therapy and mortality among patients hospitalized with heart failure and
      preserved left ventricular function--a preliminary report.
AB  - BACKGROUND: A number of medications such as beta-blockers,ACE-inhibitors,
      angiotensin receptor blockers and aldosterone antagonists, improve survival in
      patients with heart failure (HF) and reduced ejection fraction. No therapy has
      been proved to be beneficial for patients with heart failure and preserved
      ejection fraction (PLVEF). OBJECTIVES: The aim of the study was to assess the
      effect of statin therapy on all-cause mortality and cardiovascular
      rehospitalization rate in patients with HF and PLVEF during one-year follow-up.
      METHODS: We evaluated 146 patients with HF and PLVEF (ejection fraction > or =
      45%). Patients were divided into the statin therapy group (n = 103, mean age 69
      +/- 11 y, 52 men) and the group without statins (n = 43, mean age 66 +/- 16 y, 25
      men).We analysed the effects of the statin treatment prescribed to patients at
      discharge. Patients were followed up for one year. RESULTS: The age, gender, NYHA
      functional class, prevalence of co-morbidities (renal dysfunction, COPD, diabetes
      mellitus) did not differ between the groups (P = NS). Patients receiving statin
      therapy more frequently had an ischaemic aetiology of HF (79% vs. 39.5%; P <
      0.001) and hypertension (76% vs. 58%; P < 0.05). No differences in ejection
      fraction were observed neither by echocardiography (58% vs. 55%; P = NS) nor by
      basic laboratory data. Patients who received statins were often additionally
      treated with beta-blockers (91% vs. 70%; P < 0.005), aspirin (77 vs. 44%; P <
      0.01), thienopyridines (22% vs. 5%; P < 0.01) and less frequently with oral
      anticoagulants (5% vs. 23%; P < 0.005). In the group receiving statins a
      significantly lower mortality (4% vs. 21%; P < 0.001) and rehospitalization rate
      (43% vs. 69%; P < 0.05) was documented. After adjustment for all univariate
      predictors of the occurrence of study primary end-points, statin therapy was
      shown to be associated with significant and independent reduction in all-cause
      mortality (HR = 0.24 [95%CI:0.07 - 0.90] P < 0.05) and cardiovascular
      rehospitalization rate (HR = 0.55 [95%CI: 0.33 - 0.92] P< 0.05). After propensity
      matching statin therapy remained an independent factor reducing one-year
      mortality rate (HR = 0. 11 [95%CI: 0.01 - 0.99] P < 0.05]. CONCLUSIONS: This
      study showed that statin therapy may have beneficial effects on mortality and
      rehospitalization rates among patients with HF and PLVEF. It also suggests a
      potential role for statins as a new therapeutic option in patients with HF and
      PLVEF, but these observations need to be confirmed in large randomized trials.

PMID- 19157163
TI  - Prevalence of and risk factors for peripheral arterial disease among Chinese
      hypertensive patients with and without known cardiovascular disease.
AB  - INTRODUCTION: Peripheral arterial disease (PAD) is an important manifestation of
      systemic atherosclerosis.The present study was to estimate the prevalence of and
      risk factors for PAD in Chinese hypertensive patients with and without known
      cardiovascular disease (CVD) which consisted of coronary heart disease, angina,
      stroke, and transient ischaemic attack. MATERIAL AND METHODS: A cross-sectional
      study consisting of 5,186 hypertensive patients was conducted from July to
      November 2004 in Beijing and Shanghai, China. PAD was defined as an ankle
      brachial index < or = 0.90 in either leg. RESULTS: The prevalence of PAD was
      29.0% among hypertensive patients with known CVD, higher than in patients without
      known CVD (16.6%, P <0.0001). After multivariable logistic regression analysis,
      older age and current smoking were independently associated with prevalent PAD
      among all hypertensive patients.Among hypertensive patients without known CVD,
      higher total cholesterol (OR and 95% CI: 1.518, 1.162-1.984 in men and 1.460,
      1.097-1.944 in women), was independently associated with prevalent PAD. Higher
      fasting glucose (OR and 95% CI: 1.027, 1.001-1.054 in men and 1.033, 1.006-1.061
      in women) and higher uric acid (OR and 95% CI: 1.002, 1.001-1.003 in men and
      1.003, 1.001-1.005 in women) were risk factors for PAD among hypertensive
      patients with known CVD. No association was found between obesity and PAD in
      hypertensive patients with and without known CVD. CONCLUSIONS: Prevalence of and
      risk actors for PAD among Chinese hypertensive patients with and without CVD were
      different. Cessation of smoking should be stressed to inhibit the progression of
      PAD in hypertensive patients.

PMID- 19157164
TI  - Differences in atrial electromechanical coupling and atrial volume in patients
      with idiopathic paroxysmal atrial fibrillation.
AB  - OBJECTIVES: The objective of the study was to evaluate the differences in atrial
      electromechanical coupling time and atrial volume between patients with
      idiopathic paroxysmal atrial fibrillation and control subjects and to investigate
      the influencing factors of electromechanical coupling time. METHODS AND RESULTS:
      We studied 46 patients with idiopathic PAF (group IPAF) and 62 control subjects
      (group N). Doppler tissue imaging data were performed to assess atrial
      electromechanical coupling.Atrial volumes were evaluated by acoustic
      quantification.The time intervals from the beginning of the P wave to the onset
      of atrial contraction motion at the interventricular septum atrioventricular
      annulus (P-A1), left lateral mitral annulus (P-A2) in group IPAF were
      significantly longer than in group N (P < 0.01). P-A2 was correlated positively
      with left atrial (LA) anterior-posterior dimension and the largest LA volume (r =
      0.751, 0.689, P < 0.01) in the IPAF group.The longest duration of IPAF episodes
      was correlated with P-A2 (r = 0.652, P < 0.05). CONCLUSIONS: There is a
      prolongation in the atrial electromechanical coupling from the onset of the P
      wave to the beginning of the backward motion of the mitral annulus and
      interventricular septum atrioventricular annulus in patients with idiopathic PAF.
      This prolongation may be affected by left atrial size and the longest duration of
      the IPAF episodes.

PMID- 19157165
TI  - Differences in blood pressure readings between supine and sitting positions in
      hypertensive patients.
AB  - OBJECTIVE: The objective of this study was to investigate the impact of postures
      on blood pressure (BP) readings in patients with hypertension. METHODS AND
      RESULTS: BP was measured in 1,487 hypertensive patients in sitting and supine
      positions. The systolic (SBP) and diastolic (DBP) BP in supine position was 2.9
      +/- 7.8mmHg and 0.9 +/- 5.4 mmHg higher, respectively, than in the sitting
      position (P <0.001). The greatest difference between supine and sitting SBP was
      found in those aged between 30 and 39 years (3.6 +/- 6.8 mmHg), and in those who
      were older than 80 years (5.3 +/- 7.9 mmHg).A greater difference between the
      supine and sitting DBP was identified in the groups > 60-years of age.
      Multivariate regression analysis showed that age and sex were independent
      predictors for the increment of BP in the supine position. CONCLUSION: There is a
      significant difference between supine and sitting SBP and DBP, with age and sex
      being the most important predicting factors.

PMID- 19157166
TI  - Predictors of quality of life among patients undergoing coronary artery bypass
      surgery.
AB  - OBJECTIVE: Improving the quality of life (QoL) in patients with coronary artery
      disease (CAD) requires the determination of the risk factors that have an impact
      on physical functioning and mental health.The present study sought to determine
      the risk factors influencing QoL in patients with CAD and to assess the
      relationship between preoperative QoL and early outcome of CABG. METHODS AND
      RESULTS: The SF-36 questionnaire was completed through interviews with 275
      consecutive patients who underwent isolated CABG in the Tehran Heart Centre
      between May and September 2006.The present study measured the two scores of
      physical and psychological component summary scores and assessed their
      relationships with preoperative characteristics and postoperative
      complications.The mean scores of physical and psychological components were 65.78
      +/- 24.13 and 67.72 +/- 20.55, respectively. Diabetes mellitus (P = 0.007),
      family history of CAD (P = 0.032), low education level (P = 0.015), high
      Euroscore (P = 0.022), and high functional class (P <0.001) were the main
      predictors for the low physical score of QoL. In addition, female gender was
      associated with a low QoL psychological score (P <0.001). However, the elderly
      patients had a higher psychological score in comparison with the younger ones (P
      = 0.032). No relationship between the studied postoperative complications and
      preoperative psychological and physical scores was found. CONCLUSIONS: Female
      gender and lower age show specific influences on the patients' mental health. Our
      findings also indicate a major direct influence of general risk factors for CAD
      and education level on CAD patients' physical functioning before CABG.
      Nonetheless, preoperative QoL does not influence the postoperative complications.

PMID- 19157167
TI  - The association of elevated white blood cell count and C-reactive protein with
      endothelial dysfunction in cardiac syndrome X.
AB  - BACKGROUND: The aim of the study is to evaluate the association of inflammatory
      markers with endothelial function in syndrome X. METHODS: The study population
      consisted of 59 prospectively enrolled patients (28 women and 31 men; mean age,
      50.29 +/- 6.48 years) and 51 healty control subjects (18 women and 33 men; mean
      age, 51.04 +/- 7.25 years). High-sensitive CRP (hs-CRP), white blood cell (WBC)
      count and its subtypes [neutrophil (N), lymphocyte (L) and monocyte (M)] were
      measured in each subject. Endothelial function was assessed with the brachial
      artery flow-mediated dilatation (FMD) technique. RESULTS: WBC counts and hs-CRP
      levels were significantly higher in patients who had syndrome X than in control
      subjects (7.53 +/- 1.52 x 10(9) cells/L versus 6.21 +/- 1.17 x 10(9) cells/L, P =
      0.0001, and 3.11 +/- 0.63 mg/L versus 2.68 +/- 0.76 mg/L, P = 0.002,
      respectively). Neutrophil count and N/L ratio was significantly increased in
      syndrome X when compared with the control subjects (5.14 +/- 1.10 x 10(9) cells/L
      versus 4.11 +/- 0.76 x 10(9) cells/L, P = 0.0001 and 2.75 +/- 1.06 versus 2.37 +/
      0.65, P = 0.02, repectively). Other subtype counts were similar between the
      groups. FMD was impaired significantly in patients who had syndrome X in
      comparison with the control subjects (5.71 +/- 4.08% versus 16.02 +/- 4.13%, P =
      0.0001). There was a significant correlation between hs-CRP levels and FMD
      measurements (r = -0.44; P = 0.0001). Furthermore, the correlation between WBC
      count and FMD measurements were also significant (r = -0.48; P = 0.0001).
      CONCLUSIONS: The present study showed that hs-CRP and WBC count were higher in
      patients with syndrome X than in control subjects. Furthermore, endothelial
      function was impaired significantly in patients with syndrome X.The increased
      levels of hs-CRP and WBC count may suggest that these markers may be used in
      clinical practice for the assessment of the inflammatory status of the
      endothelium in syndrome X.

PMID- 19157168
TI  - Risk scores in ischaemic heart disease patients with type 2 diabetes, Isfahan,
      Iran.
AB  - OBJECTIVE: The aim of this study was to determine a simple risk score for
      undiagnosed ischaemic heart disease (IHD) in patients with type 2 diabetes.
      METHODS: A sample of 2101 patients was taken from case records of diabetic
      patients held by the Isfahan Endocrine and Metabolism Research Centre outpatient
      clinic.The study was performed cross-sectionally. The following risk factors were
      analysed for developing a risk score among the patients: sex, age, duration of
      diabetes, body mass index, blood pressure, glycosylated haemoglobin, fasting
      blood sugar, cholesterol, triglycerides and smoking.A logistic regression model
      was used to compute the odds ratio (OR) for risk factors for diagnosed IHD. ORs
      of the models were used to assign a score value for each variable and the
      composite diabetes risk score was calculated as the sum of those scores. RESULTS:
      66% of patients were women and 36.8% patients had IHD. ROC curves were
      constructed to identify the optimum discriminator (> or = 54 from 100) of
      diabetic patients for determining IHD. Sensitivity and specificity for predicting
      IHD were calculated for different cut-off scores. The sensitivity and specificity
      for IHD were around 64% and 57%, respectively. CONCLUSION: The present study
      focused on predicting ischaemic heart diseases in type 2 diabetes from factors
      that are easy to measure with non-invasive methods known to be associated with
      risk of IHD, using a risk score.

PMID- 19157169
TI  - Effect of cardiac resynchronization therapy on mean platelet volume.
AB  - OBJECTIVE: Cardiac resynchronization therapy (CRT) increases cardiac performance
      and decreases morbidity and mortality in patients with heart failure. Mean
      platelet volume (MPV), a marker of platelet hyperreactivity, was found to be
      increased in both chronic heart failure and thromboembolic events. Systemic and
      pulmonary thromboembolism is a frequent complication of heart failure.The aim of
      this study is to determine the effects of cardiac resynchronization therapy on
      MPV values. METHODS AND RESULTS: Fifty-six heart failure patients with increased
      QRS duration underwent biventricular pacemaker implantation. Blood samples were
      collected the morning before implantation and at six months follow-up. Response
      criteria were: an increase in ejection fraction of more than 10% from baseline at
      six months or no hospitalization for major cardiac events during the first six
      months.The mean MPV values were decreased from 9.3 +/- 0.5 fl to 8.3 +/- 0.5 fl.
      Patients with recorded major cardiac events in the follow-up period had no
      statistically significant decrease in MPV values. CONCLUSIONS: In our study we
      found that cardiac resynchronization therapy leads to a decreased MPV and
      clinical improvement in patients with heart failure that is accompanied with a
      decrease in MPV.

PMID- 19157170
TI  - Combined "pro-atherosclerotic" variants of the ACE and APOE genes increase the
      risk of the coronary artery disease associated with the presence of cigarette
      smoking.
AB  - OBJECTIVE: Cigarette smoking increases the synthesis of angiotensin-1 converting
      enzyme (ACE) and induces oxidative modifications of the apolipoprotein E (apo
      E).Thus we explored the gene-environment interactions between APOE gene epsilon
      and ACE gene insertion/deletion polymorphisms and cigarette smoking in coronary
      artery disease (CAD) patients. METHODS: We analysed 360 subjects: 171 CAD
      patients and 189 blood donors without a history of cardiovascular diseases. ACE
      and APOE polymorphisms were genotyped using polymerase chain reaction (PCR) and
      restriction fragment length polymorphism (RFLP) methods, respectively. To
      determine gene-environment interactions, epidemiological methodology was used.
      RESULTS: The ACE DD genotype was a rather weak risk factor of CAD in the analysed
      population (OR = 1.87, P = 0.01).The differences in allele and genotype
      distribution of the APOE polymorphism were not statistically significant.The
      carriers of the combined genotype ACE(DD) +
      APOE(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) were more frequent in
      patients, however, the differences were on the bound of statistical significance
      (P = 0.08). Logistic regression analysis showed that the ACE(DD) + apo
      E(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) cigarette smokers were much
      more frequent in the CAD group (OR = 11.68, 95%CI; 1.52-246.43, P = 0.009).We
      confirmed these results using the 4 x 2 table approach and we found a synergistic
      effect of the ACE(DD) + APOE(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4)
      combined genotype and cigarette smoking (SI = 10.52, SIM = 6.09). CONCLUSIONS: We
      demonstrated the existence of the synergistic effect between cigarette smoking
      and the contemporaneous carrier-state of APOE epsilon4 and ACE D alleles which
      increased the risk of CAD to a large extent.

PMID- 19157171
TI  - Apo-B/apo-AI ratio: a better discriminator of coronary artery disease risk than
      other conventional lipid ratios in Indian patients with acute myocardial
      infarction.
AB  - BACKGROUND: Coronary artery disease (CAD) is a leading cause of morbidity and
      mortality in the developed world and is rapidly assuming epidemic proportions in
      developing countries including India. This has led to extensive research to
      determine the risk factors unique to this group which may predispose to the
      elevated risk of this disease. Important amongst them are lipoproteins,
      homocysteine, lipoprotein (a), pro-inflammatory cytokines etc. The following
      study was undertaken to evaluate the role of the apolipoprotein-B100 (apo
      B)/apolipoprotein-AI (apo-AI) ratio as a predictor of CAD risk in the
      atherosclerosis-prone Indian population, as compared to other conventional lipid
      ratios. MATERIAL AND METHODS: The study group comprised 100 clinically assessed
      patients with acute myocardial infarction (AMI) diagnosed on electrocardiographic
      and biochemical criteria and 100 age-matched healthy control subjects. Apo-B and
      apo-AI levels were estimated by the immunoturbidimetric method, using kits from
      Randox, UK. Lipid profile was determined using standard enzymatic methods. The
      exponential regression coefficient beta was calculated for total cholesterol/high
      density lipoprotein cholesterol (TC/HDL), TC-HDL/HDL, low-density lipoprotein (
      LDL) cholesterol/HDL and apo-B/apo-AI ratios. RESULTS: The TC/HDL ratio was 5.15
      +/- 1.7 and 3.45 +/- 0.87 in patients with AMI and control subjects, respectively
      (P< 0.001). The TC-HDL/HDL ratio was 4.61 +/- 2.6 and 2.22 +/- 1.14 in the
      patients with AMI and the control subjects (P <0.001). The LDL/HDL ratio was 3.32
      +/- 1.5 in the AMI patients and 1.84 +/- 0.78 in the control subjects (P <
      0.001); whilst the apo-B/apo-AI ratio in the patients with AMI was 0.96 +/- 0.30
      and 0.71 +/- 0.20 in the control subjects (P <0.001). The exponential value of
      the regression coefficient beta (Exp [beta]) for apo-B/apo-AI ratio was 111.9, as
      compared to 4.4 for the LDL/HDL ratio, 3.5 for the TC/HDL ratio and 2.2 for the
      TC-HDL/HDL ratio, though all the lipid ratios were significantly higher in cases
      than in control subjects. CONCLUSION: Our findings suggest that the apo-B/apo-AI
      ratio is a better discriminator of CAD risk in the atherosclerosis-prone Indian
      population, than any of the conventional lipid ratios. The reduction of value of
      the apo-B/apo-AI ratio may drastically decrease the risk for CAD. Hence, the apo
      B/apo-AI ratio may be suggested as an alternative to other lipid ratios fo risk
      assessment in patients with CAD.

PMID- 19157172
TI  - Breviscapine, a traditional Chinese medicine, alleviates myocardial ischaemia
      reperfusion injury in diabetic rats.
AB  - OBJECTIVE: The aim of this study was to explore the effects of breviscapine on
      the expressions of intercellular adhesion molecule-I (ICAM-I), ATPase activities
      and oxidative stress in ischaemia-reperfused (I/R) myocardium of diabetic rats.
      METHODS: Sprague Dawley rats were randomly divided into two groups (a diabetic
      group and a non-diabetic group), and each group divided into two subgroups
      including a control group and a breviscapine group. Reperfusion surgery was
      carried out in all rats.The contents of malonaldehyde (MDA), superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-P(x)) in serum and myocardial tissues were
      measured. The activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase in
      myocardial mitochondria were measured. The ICAM-I protein expressions in
      myocardium were determined with the immunohistochemical method. RESULTS: The
      activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase were significantly
      increased in diabetic rats in the breviscapine group compared with the control
      group. Compared with the non-diabetic control group, the contents of MDA in serum
      and myocardium were significantly increased in the diabetic control group.
      Breviscapine led to a reduction of the contents of MDA in the diabetic and non
      diabetic group. Compared with the non-diabetic control group, the activities of
      SOD and GSH-P(x) in the myocardium were significantly decreased in the diabetic
      control group.The activities of SOD and GSH-P(x) in serum and myocardium were
      increased in the diabetic and non-diabetic group after breviscapine treatment.
      Compared with the non-diabetic control group, the ICAM- I protein expressions
      were increased significantly in the diabetic control group. Breviscapine
      decreased the ICAM-I protein expression in the diabetic and the non-diabetic
      group. CONCLUSION: Breviscapine may have protective effects on myocardial
      ischaemia reperfusion injury of diabetic rats by scavenging oxygen free radicals,
      decreasing the expressions of ICAM-I protein in myocardium and increasing the
      activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase in myocardial
      mitochondria.

PMID- 19157173
TI  - Gender differences in risk factors and outcomes after cardiac rehabilitation.
AB  - OBJECTIVE: We compared the baseline characteristics, cardiovascular risk factors
      and outcomes between men and women in an Iranian cardiac rehabilitation programme
      after adjusting for age, body mass index and waist-to-hip ratio. METHODS: In a
      self-controlled descriptive study performed between 1996 and 2006, we evaluated
      547 patients with documented coronary heart disease before and after a 24-session
      cardiac rehabilitation programme. RESULTS: Women were older, more likely to be
      obese, anxious, depressed, and had more traditional coronary heart disease risk
      factors than men. At baseline, exercise capacity was lower (P < 0.001), but total
      cholesterol (P < 0.001), high-density lipoprotein cholesterol (P = 0.007), low
      density lipoprotein cholesterol (P = 0.001), fasting blood sugar (P = 0.002),
      left ventricular ejection fraction (P < 0.001), systolic blood pressure (P <
      0.001), diastolic blood pressure (P < 0.001), and heart rate (P = 0.016) were
      higher in women.Although there was significant improvement in most of the
      variables and risk factors after cardiac rehabilitation, changes were not
      statistically significant between men and women except for significantly more
      improvement in exercise capacity (P < 0.001) and less reduction in body mass
      index (P = 0.04) in men. CONCLUSION: Following a short-term cardiac
      rehabilitation programme, modification in cardiac risk factors and quality of
      life occurs. Both genders benefit alike in most aspects from this programme.

PMID- 19157174
TI  - Advances in the management and surveillance of patients with aortic coarctation.

PMID- 19157175
TI  - Echocardiographic assessment of patients with heart failure: a practical
      checklist.

PMID- 19157176
TI  - A giant coronary sinus mimicking descending aorta.
AB  - A 58-year-old male patient was admitted to the emergency service with
      dyspnoea.The patient underwent several laboratory and imaging tests including
      echocardiography and a diagnosis of descending aortic aneurysm was
      suspected.After computerised tomography scanning, a normal-size descending aorta
      was found so that echocardiography was done once more. Intravenous contrast
      examination revealed a giant coronary sinus in this patient.

PMID- 19157177
TI  - Endovascular treatment in a patient with recurrent angina.
AB  - The left internal mammary artery (IMA) is the preferred native graft for left
      anterior descending revascularisation owing to its favourable long-term patency
      and resistance to atherosclerosis. Incomplete ligation of the IMA side branches
      may cause recurrent angina due to flow diversion. Reoperation for ligating this
      unligated side branches may be performed but damage to the internal mammary
      artery or saphenous graft are the potential complications of this
      procedure.Therefore less invasive endovascular methods should be preferred. In
      this paper we report a patient with recurrent angina due to a large unligated
      left internal mammary artery side branch that was succesfully treated with
      percutaneous coil embolisation.

PMID- 19157179
TI  - [Concerning abuse....].

PMID- 19157178
TI  - Retrograde embolization after balloon angioplasty in a patient with late stent
      subthrombosis in a paclitaxel-eluting stent.
AB  - We report on a 65-year-old patient who underwent a semi-urgent percutaneous
      coronary intervention (PCI) for a very late stent subthrombosis (13 months) in a
      paclitaxel-eluting stent (PES) while still on dual antiplatelet therapy.The
      procedure was complicated by a retrograde embolization into the circumflex artery
      (CFX). We will focus on the risk of distal embolization after primary PCI for
      acute stent thrombosis and its prevention.

PMID- 19157180
TI  - [The year of reforms, 2009 will also be that year for nurses].

PMID- 19157181
TI  - [Ethics as the essence of nursing].

PMID- 19157182
TI  - [The charter of disease from 1974 to today].

PMID- 19157183
TI  - [How should one characterize and envision an ethical clinical situation?].

PMID- 19157184
TI  - [Limiting and stopping resuscitation, an ethical consideration].

PMID- 19157185
TI  - [Ethical reflections on nursing practices in a death chamber].

PMID- 19157186
TI  - [Consultations about ethical practices and cultural diversity].

PMID- 19157187
TI  - [Contribution and role of kindness in ethical consideration].

PMID- 19157189
TI  - [An ethical concept of dignity and democracy].

PMID- 19157188
TI  - [Ethics and cost of activities].

PMID- 19157190
TI  - [Roselyne Gentric or the determination to become a nurse].

PMID- 19157191
TI  - [Disease transmission, an uncontrolled element in quality nursing].

PMID- 19157192
TI  - [Role of the nurse at the heart of a pain unit].

PMID- 19157193
TI  - [Atherosclerosis prevention at a heart unit].

PMID- 19157194
TI  - [Definite case of tuberculosis].

PMID- 19157195
TI  - [Maintaining understanding, supporting reassurance].

PMID- 19157196
TI  - [Charles Krafft (1863-1921].

PMID- 19157197
TI  - [Main illegal drugs consumed in France].

PMID- 19157198
TI  - [Taking action in the war against AIDS as an example of solidarity].

PMID- 19157199
TI  - [Chronic lymphocytic leukemia].
AB  - Chronic lymphocytic leukemia results from a proliferation/accumulation of
      monoclonal B lymphocytes. The diagnosis is easily made on blood cytology and
      immunophenotype. The complexity of mechanisms which govern the clonal evolution
      translate in a large pronostic diversity on long-term outcome, with a life
      expectancy ranging from a few years to more than 25 years in the most indolent
      forms. Prognostic appraisal is currently based on clinical and hematological
      presentation, whereas cytogenetics, immunoglobulin gene status, expression of
      proteins involved in cell proliferation such as ZAP70 or CD38 provide more
      precise but non routine indications. Although there is a lot of effective drugs
      against the clonal process, any of them are curative, and long term benefit of
      treatment tailored on individual prognostic features still deserves further
      studies. Therefore, current treatment recommendations aim at sustaining quality
      of life in elderly patients, whereas response quality and length are the main
      targets in younger ones.

PMID- 19157200
TI  - [Alveolar haemorrhage in leptospirosis].

PMID- 19157201
TI  - [Peripheral neuropathies: major diagnostic and therapeutic advances].

PMID- 19157202
TI  - [What is a peripheral neuropathy?].
AB  - Peripheral neuropathies may be classified according to the localisation of
      symptoms and signs. This step necessitates a good knowledge of the peripheral
      nervous system anatomy. The diagnostic strategy relies on this classification and
      allows, thanks to the neurophysiological exam to establish the pathogenic
      mechanism of the neuropathy. These data are important to limit the possible
      aetiologies to a reasonable number in order to use the appropriate paraclinical
      work-up. Laboratory examinations may be simple or sophisticated and their use may
      require the help of an expert center. In a limited number of cases, nerve biopsy
      is still a very useful tool to determinate the mechanism of peripheral neuropathy
      and to guide the treatment.

PMID- 19157203
TI  - [Neurological electrophysiology].
AB  - The electroneuromyogram (ENMG) is currently used and deserves to be realized in
      all cases where a peripheral nervous system affection is present. The ENMG has a
      proper semiology which correspond to an underlying peripheral nerve, muscular or
      of the neuromuscular junction pathology. It allows to evaluate the neuromuscular
      pathologies and to precise the physiopathological process. It allows to
      differentiate the peripheral nerve disorders from primary muscular disorders.
      Within the peripheral nervous system disorders, it allows to separate the axonal
      from the demyelinating lesions. The ENMG allows also to evaluate the severity of
      the affection and to predict the possibilities of reinnervation.

PMID- 19157204
TI  - [Dysimmune neuropathies: current diagnosis and therapy].
AB  - Dysimmune neuropathies encompass an acute form, Guillain-Barre syndrome (GBS),
      and mainly 3 chronic forms: chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP), multifocal motor neuropathy, and polyneuropathy
      associated with anti-MAG (myelin-associated-glycoprotein) IgM monoclonal
      gammopathy. Recent concepts have concerned both incidence and mortality rates,
      and better scoring system for predict outcome in GBS, but new therapeutical
      strategy is needed for the so-called "benign" forms and for relapsing forms after
      first-line IVIg therapy. In chronic forms, criteria for diagnosis and guidelines
      for management have been edited in the recent years, together with
      recommendations for outcome measures. However, there is still a need for knowing
      the better outcome measures, and to elaborate new trials, mainly focusing on the
      long-term management of the patients.

PMID- 19157205
TI  - [Vasculitis multiple mononeuropathies].
AB  - The impairment of the peripheral nervous system is frequent in primary or
      secondary vasculitis. The diagnosis of painful multiple mononeuropathy requires
      neuromuscular biopsy. Distal sensorimotor polyneuropathies are misleading.
      Therefore clinical and electrophysiological asymmetry is helpful. Steroids and
      cytotoxic agents have been the mainstay of therapy for most vasculitic
      neuropathies but therapeutic strategies may vary for ANCA-associated vasculitis.

PMID- 19157206
TI  - [Metabolic neuropathies].
AB  - Due to the high prevalence of diabetic neuropathies, metabolic neuropathies are
      common. "Diabetic neuropathy" is a slowly progressive painful sensory neuropathy
      evolving with a length dependent pattern. Slight distal weakness of toes extensor
      can be observed. Trophic changes and autonomic neuropathy can lead to severe
      complications (diabetic foot ulceration or symptomatic postural hypotension).
      Multifocal neuropathies can also be encountered with diabetes. With such
      neuropathic pattern, other causes of neuropathy should be excluded and patients
      should be referred to specialised centres. Other metabolic neuropathies can
      occur, especially alcoholic neuropathies and uremic neuropathies. Laboratory
      tests are an important part in the diagnostic procedure to look for a metabolic
      cause.

PMID- 19157207
TI  - [Drug induced neuropathies].
AB  - The search for a peripheral neuropathy must be systematic when a toxic medicament
      for the peripheral nervous system is prescribed as well as the search for a drug
      induced neuropathy is part of the screening of any peripheral neuropathy, but for
      numerous drugs, the imputability is not strictly demonstrated. A drug induced
      neuropathy must be differentiated from a neuropathy related to the disease for
      which the drug was prescribed. It is the case in the course of some cancers and
      or AIDS. Moreover, the intake of a neurotoxic drug can aggravate a pre-existing
      neuropathy. Electrophysiological study is important to confirm the neuropathy, to
      specify the type, more often axonal, and the severity, and also to detect
      infraclinical signs of neuropathy before the beginning of the treatment. Many of
      these drug induced neuropathies are reproducible in animals, that is useful to
      try to diminish the neurotoxicity in human beings. Antineoplastic chemotherapies
      and antibiotics are most often implicated in drug induced neuropathies.

PMID- 19157208
TI  - [Hereditary neuropathies].
AB  - Although there are many human hereditary neuropathies, most of them with the
      exception of Charcot-Marie-Tooth disease or hereditary sensorimotor neuropathy,
      are rare. Irrespective of their type, the mode of transmission may be autosomal
      dominant or recessive, or X-linked. The most difficult to diagnose, however, are
      the sporadic forms. It is customary to distinguish the cases in which the
      neuropathy is the sole clinical expression from multisystemic diseases where
      neuropathy is one component of multi-organ involvement. The complexity and the
      multiplicity of genes involved and the lack of understanding of their exact
      functions hinder logical presentation of these hereditary neuropathies. For
      understandable technical reasons, the stage of specific treatment, namely the
      repair of the mutated gene, has yet to be attained.

PMID- 19157209
TI  - [Patient record: what is Charcot-Marie-Tooth disease?].

PMID- 19157210
TI  - [Evidence based medicine: fatherhood and filiation].

PMID- 19157211
TI  - [Septicemia].

PMID- 19157212
TI  - [Systemic lupus erythematosus. Anti-phospholipid syndrome].

PMID- 19157213
TI  - [Osteomyelitis and septic arthritis. Vertebral osteomyelitis].

PMID- 19157214
TI  - [The electrocardiogram. Indications and interpretation].

PMID- 19157215
TI  - [Plague: Marcel Baltazard, Pasteur's follower].

PMID- 19157216
TI  - [Treatment of atopic dermatitis in children].

PMID- 19157217
TI  - [Identification of Amaranthus palmeri pollen allergens comparing recognizing
      pattern between allergic and non-allergic].
AB  - BACKGROUND: Amaranthus palmed pollen is an important allergenic agent in Mexico.
      A high proportion of subjects allergic to pollen grains are allergic to this
      species. In this study, we analyzed the different response of three groups: one
      of patients allergic to A. palmeri; one of patients allergic to other pollen
      species different from A. palmeri, and one of non-allergic subjects. OBJECTIVE:
      To identify proteins that are recognized preferentially by patients allergic to
      A. palmeri that could be considered as its allergens. MATERIAL AND METHODS: T
      cell response was determined by lymphoproliferative assays with eight protein
      fractions in the range of 14 to 103 kDa obtained by electroelution, and the total
      protein extract. IgE recognition was determined by Western blot. RESULTS: Even
      though some individuals in the three groups showed cellular responses to some of
      the protein fractions, as well as IgE recognition of the pollen proteins, the
      allergic subjects had the strongest responses on average. Preferential
      recognition of some proteins was evident in A. palmeri pollen allergic patients.
      CONCLUSIONS: Differences among the three groups were not statistically
      significant. However, we found four proteins with molecular weights of 17.9,
      20.1, 26.6 and 66.5 kDa, which can be proposed as allergens.

PMID- 19157218
TI  - [Association among familial atopy, smoking (passive and active), allergic
      rhinitis, labor environment and adult asthma].
AB  - BACKGROUND: Studies of association among parental atopy, tobacco exposure
      (passive or active) and adult asthma have provided conflicting results.
      OBJECTIVE: To determine the relationship among parental atopy, smoking, exposure
      to tobacco smoke, allergic rhinitis, work environment and asthma in adults.
      MATERIAL AND METHODS: In a population of 329,219 inhabitants of a geographically
      defined area in Northeastern of Mexico, we identified 791 cases of asthma. The
      patients were 20 to 54 years old, and were divided in three groups: with asthma
      in remission (263 patients), with symptoms since childhood (270 patients), and
      with asthma onset in adult age (258 patients). We included 793 randomly selected
      control subjects. Information on family atopy, passive and active smoking,
      allergic rhinitis and workplace conditions were collected by using a
      questionnaire. RESULTS: Parental atopy history, active smoking, allergic rhinitis
      and pollution in the workplace induce asthma symptoms. Exposure to smoking is a
      risk factor of persistence of asthma symptoms in adults (OR = 1.33; IC 95%, 1.07
      1.66), but no of their development (OR = 1.10; IC 95%, 0.87-1.39). Working in a
      polluted environment had not significance in remission of asthma (OR =1.32; IC
      95%, 0.95-1.85). CONCLUSIONS: Results support hypothesis that family atopy,
      active smoke, allergic rhinitis and pollution favor the persistence of asthma
      symptoms and increase the risk of asthma in adults.

PMID- 19157219
TI  - [Pulmonary gammagraphy study in asthmatic children with gastroesophageal reflux].
AB  - BACKGROUND: The asthmatic children who do not respond favorably to the
      specifically anti-allergic treatment, and also begin their breathlessness crisis
      preferably at night, are suspicious of suffering gastric-esophagus reflux that
      stimulate bronchial spasm crisis by means of an aspiration mechanism, or more
      frequently, by means of a reflective mechanism through the vagal via. OBJECTIVES:
      To know probable physiopathologic mechanism of gastric-esophagus reflux that
      exacerbates asthmatic crisis. To know digestive symptoms associated to
      respiratory process. To evaluate clinic evolution of children after antireflux
      treatment. MATERIAL AND METHODS: There were chosen 50 moderate-severe persistent
      asthmatic patients with non favorable evolution and gastric-esophagus reflux. The
      diagnosis was settled by means of radiological study, with barium contrast in
      esophagus, stomach and duodenum, and esophagus-pulmonary gammagraphy with
      technetium 99 (99mTc). Besides, a searching of bronchial aspiration signs with
      the isotopic exploration was carried out. RESULTS: It was demonstrated that 38%
      of all cases had bronchial microaspirations and 30% did not have digestive
      symptoms associated to the respiratory process. Patients were subjected to an
      antireflux treatment and 78% of them considerably improved their asthmatic crisis
      after the treatment. CONCLUSIONS: 38% of the cases showed bronchial
      microaspirations in pulmonary gammagraphy. The more probable physiopathologic
      mechanism was vagal via, because 62% of the patients did not have bronchial
      aspiration signs. There were no digestive symptoms (silent reflux) in 30% of the
      children. Asthmatic crisis evolved favorably in 78% of the cases after antireflux
      treatment.

PMID- 19157220
TI  - Comparative mites and cockroaches sensitization study in three cities of Mexico.
AB  - BACKGROUND: In Mexico there are few research papers dealing with mites and
      cockroaches sensibilizing in patients suffering from respiratory allergies and
      even less susceptibility comparative studies to the same between cities having
      different climatic and geographic characteristics. OBJECTIVES: To research in a
      prospective study skin sensibilizing to eighy different mites and two cockroaches
      species in patients with respiratory allergies in three cities of Mexico:
      Monterrey, NL, Tampico, Tamps., and Irapuato, Gto., in order to determine if
      there are sensibilizing differences due to climatic and geographic conditions.
      PATIENTS AND METHODS: Skin tests were performed by scarification in 58 patients
      suffering diverse respiratory allergies such as bronchial asthma, allergic
      rhinitis, allergic rhinoconjunctivitis and combinations of the same. Tests were
      performed on 18 patients from Monterrey, 20 from Tampico and 20 from Irapuato.
      Mites used were: Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia
      tropicalis, Tyrophagus putrescientiae, Lepidoglyphus destructor, Euroglyphus
      maynei, Acarus siro, Dermatophagoides microceras and 2 cockroaches species,
      Periplaneta americana and Blatella germanica. RESULTS: Of the total 58 patients,
      the most important and frequent reactions were produced by D. pteronyssinus, D.
      farinae and E. maynei, which were found in 40, 33 and 32 patients respectively,
      then D. microceras in 21 patients, A. siro in 18, and B. tropicalis in 13
      patients. In Tampico, the mite with the most frequent susceptibility was E.
      maynei, in Monterrey and Irapuato the most relevant were D. farinae and D.
      pteronyssinus, respectively. In Tampico, B. tropicalis was positive in 8 patients
      vs only 4 in Monterrey and 1 in Irapuato. The skin response to cockroaches was
      not important and the city with most positives was Irapuato with 6 patients
      responding to B. germanica, and 3 to P. americana; in Tampico 5 patients reacted
      to P. americana and 3 to B. germanica, and in Monterrey skin reactivity was
      slight and only 2 patients reacted to P. americana and 1 to B. germanica. Only 2
      patients out of 58 in the study resulted in negative skin tests to mites and
      cockroachs allergens. CONCLUSIONS: Only 2 patients out of 58 in the study
      resulted in negative skin tests, which demonstrates the high sensibilizing
      capacity from mite and cockroach allergens in patients suffering from respiratory
      allergies. Although the patient group is small, it reveals that mites from the
      Pyroglyphidae families D. pteronyssinus, D. farinae and E. maynei are the most
      sensibilizing in the three cities under research, without regards of geographic
      and climatic conditions as they were the most frequent skin reactants and
      produced greater skin symptoms in patients, with several differences in respect
      to skin reactivity, as they were greater in Monterrey than Tampico and Irapuato.
      Although there is crossed reactivity between mites of the Pyroglyphidae family,
      it might be convenient to routinely include E. maynei in the skin test panel
      practiced to patients with respiratory allergies in the cities under research,
      and maybe also B. tropicalis in Tampico. In comparison with mites, cockroaches
      produced little skin reactivity in the patients.

PMID- 19157221
TI  - [Severe asthmatic crisis in pediatric intensive care. A 10-year-study].
AB  - BACKGROUND: Asthma is a severe health problem all over the world about morbidity
      and mortality, whose repercussions on the patients and their family require
      coordinated actions. OBJECTIVE: To know the characteristics of hospitalizations
      due to asthma severe crises in pediatric intensive care units of a Cuban
      province. MATERIAL AND METHODS: A prospective and retrospective study was done
      with 40 pediatric patients with discharge diagnosis of severe crisis of asthma
      coming from the pediatric intensive care unit of Hospital Jose Marti y Perez,
      from January 1st, 1996 to December 31st, 2005. Main variables were: patients'
      origin, age at the moment of diagnosis and hospitalization, sex, familial history
      of atopy, triggering factors, previous inter-crises treatments, complications and
      hospitalization time. RESULTS: Patients discharged due to this disease are little
      respect to other causes. Municipalities of higher prevalence of severe crisis
      were Fomento and Sancti Spiritus. Generally, patients had lesser than five years
      of age at the beginning of the disease and at the moment of hospitalization; male
      sex predominated and showed positive history of allergy. The most frequent
      triggering factors were respiratory infections and atmospheric changes. Most
      patients did not receive inter-crises treatments. The most common complications
      were: acid-base balance disorders and broncopneumonias. Hospitalization time was
      lesser than three days. CONCLUSIONS: Acute crises of asthma in pediatric patients
      should be identified early to initiate the proper treatment and prevent
      complications.

PMID- 19157222
TI  - [CXCR4 combined with P504S or P63 in differential diagnosis of benign and
      malignant prostatic diseases].
AB  - OBJECTIVE: To evaluate the application of CXC chemokine receptor-4 (CXCR4)
      combined with alpha-methylacyl-CoA racemase (P504S) or P63 protein in the
      differential diagnosis of benign and malignant prostatic diseases. METHODS: The
      EnVision immunohistochemical method was used to detect the expressions of CXCR4,
      P504S and P63 protein in 40 specimens of PCa not treated by any anticancer
      therapy and 30 specimens of BPH tissues. The correlation was analyzed between
      CXCR4 expression and the characteristics of PCa metastasis. RESULTS: Of the 40
      cases of PCa, 33 (82.5%) were stained positive for CXCR4, 37 (92.5%) for P504S
      and 2 (5%) for P63 protein. Of the 30 cases of BPH, 5 (16.6%) exhibited
      positivity for CXCR4, 1 for P504S and all for P63. P504S + P63 showed a higher
      rate of correct diagnosis of PCa than either CXCR4 + P63 or P504S + CXCR4. There
      was a statistically significant correlation between CXCR4 expression and cancer
      metastasis (P < 0.05). CONCLUSION: P504S, CXCR4 and P63 are useful tumor markers
      for the diagnosis and differentiation of benign and malignant prostatic diseases.
      CXCR4 gives a high rate of correct diagnosis when combined with P504S or P63, and
      has an important application value in the differential diagnosis of benign and
      malignant prostatic diseases.

PMID- 19157223
TI  - [The feeder layer of human embryonic fibroblasts supports the growth of human
      spermatogonial stem cells].
AB  - OBJECTIVE: To investigate the methods and conditions for the isolation,
      purification and culture of human spermatogonial stem cells (SSCs) on the feeder
      layer cells of human embryonic fibroblasts (hEFs). METHODS: SSCs isolated and
      purified from normal human fetal testicular tissues by sequential two-step enzyme
      digestion and Percoll uncontinuous density gradient centrifugation were cultured
      on the feeder layer cells of hEFs isolated from 5-9 weeks old human embryos. The
      surface markers SSEA-1 and OCT4 of the SSCs were detected by
      immunohistochemistry; the alkaline phosphatase (AKP) activity of the SSC clones
      measured; and the expressions of the SSC-related genes determined by RT-PCR.
      RESULTS: SSCs survived, proliferated and formed colonies on the feeder layers,
      and the colonies were highly positive for SSEA-1 and OCT4, with strong AKP
      activity and high expressions of the SSC-related genes. CONCLUSION: The feeder
      layer of hEFs supports the growth of human spermatogonial stem cells.

PMID- 19157224
TI  - [Association of gene polymorphisms of cytokine and cytokine receptor with type
      III prostatitis].
AB  - OBJECTIVE: To explore the role of the gene polymorphism of cytokine and cytokine
      receptors in the pathogenesis of type III prostatitis. METHODS: We genotyped 24
      outpatients diagnosed with type III prostatitis and 51 healthy volunteer controls
      for the single nucleotide polymorphisms of 13 cytokines and cytokine receptors at
      22 sites by Sequence Specific Primer -PCR (SSP-PCR). RESULTS: The patients
      exhibited significantly higher frequencies of the genotypes of IL-10-819 T/T
      (62.5%) and IL-10-592 A/A (62.5%), the haplotype of IL-10 (-1082/-819/-592) ATA
      (75.0%) and the diploid genotype of IL-10 (-1082/-819/-592) ATA/ATA (62.5%), than
      with the healthy controls (31.3% , 31.3%, 25.0% and 31.2%) (P < 0. 05).
      CONCLUSION: Our data suggested that anti-inflammation cytokine IL-10 gene
      polymorphisms were associated with the pathogenesis of type III prostatitis.

PMID- 19157225
TI  - [Construction of urethra mucosa structure in vitro by tissue engineering].
AB  - OBJECTIVE: To construct a structure of urethra mucosa in vitro by tissue
      engineering. METHODS: Primary porcine urothelial cells (UC) were obtained from
      the porcine bladder by enzymatic digestion and detected by immunofluorescence and
      RT-PCR. Bladder acellular matrix grafts (BAMG) were prepared, used as the
      scaffold and then evaluated by HE staining, Masson's trichrome staining,
      immunohistology and scanning electron microscopy. After in vitro culture and
      amplification, the UCs were seeded on the luminal surface the BAMGs. RESULTS:
      After 1 week of in vitro culture, the UCs formed a multilayer structure on the
      luminal surface of the BAMGs along the basement membrane. The tissue-engineered
      urothelium and BAMG complex was well formed and pan cytokeratins were positively
      expressed in the UCs on the scaffold. CONCLUSION: By tissue engineering, the
      urethra mucosa structure can be rapidly constructed in vitro, which can be
      applied to the repair of such urethral defect as hypospadias and urethral
      stricture.

PMID- 19157226
TI  - [Influence of SNCG transfection on the effectiveness of anti-tumor drugs in PC-3
      cell lines].
AB  - OBJECTIVE: To observe the sensitivity of the PC-3 cell lines transfected with the
      PCI-NEO-SNCG plasmid to Cisplatin (DDP), 5-Fluorouracil (5-FU), Adriamycin (ADM),
      Vincristine (VCR) and Paclitaxel (TAX), and to explore the influence of the SNCG
      expression on the effectiveness of anti-tumor drugs. METHODS: The plasmids PCI
      NEO and PCI-NEO-SNCG were transfected into the hormone-independent prostate
      cancer cell lines PC-3. RT-PCR was adopted to examine the expression of SNCG in
      the PC-3 cell lines. The MTT method was employed to detect the suppressive
      effects of different anti-tumor drugs (DDP, ADM, 5-FU, VCR and TAX) on the cell
      lines transfected with PCI-NEO and PCI-NEO-SNCG. Flow cytometry was used to
      analyze the cell cycles and apoptosis of the transfected cells treated with TAX.
      RESULTS: The 5 anti-tumor drugs suppressed the growth of the cell lines
      transfected with the plasmids PCI-NEO and PCI-NEO-SNCG in a time-dependant
      manner. The comparison between the growth-suppressing effects of different anti
      tumor drugs on the PC-3 cell lines showed no significant differences between the
      group transfected with PCI-NEO and that with PCI-NEO-SNCG in DDP, 5-FU, ADM and
      VCR (P > 0.05), while the rate of suppression of TAX on the latter cell lines was
      significantly lower than that on the former (P < 0.01). Compared with the PCI-NEO
      SNCG plasmid transfected cell lines, after treated with TAX for 48 hours, those
      transfected with the PCI-NEO plasmid exhibited a significantly larger proportion
      of cells remaining in the G2-M stage (P < 0.01), a smaller proportion in the G0
      G1 and S stages (P < 0.01) and a significantly higher expression of Caspase-3 (P
      < 0.01). CONCLUSION: The significant reduction of the growth-suppressing effect
      of TAX in the SNCG-transfected PC-3 cell lines suggests that the expression of
      SNCG may restrain the effect of TAX. These findings have provided evidence and
      guide to the individual chemotherapy of prostate cancer.

PMID- 19157227
TI  - [Establishment of human embryonic stem cell line NJGLLhES1].
AB  - OBJECTIVE: To report the derivation and characterization of a new human embryonic
      stem cell (hESC) line NJGLLhES1. METHODS: From the inner cell mass of frozen
      thawed human embryos and with ICR mouse embryonic fibroblasts as the feeder
      layer, we established a new human embryonic stem cell line, which was named
      NJGLLhES1. We detected the karyotype of the cell line, determined the expressions
      of alkaline phosphatase, the specific cell surface antigens SSEA-3, SSEA-4, TRA-1
      60, TRA-1-81 and the marker gene Oct-4, and examined the formation of embryoids
      and teratomas. RESULTS: NJGLLhES1 was maintained for over 1 year in vitro, with
      the morphological characteristics of hESC, a normal karyotype, positive
      expressions of alkaline phosphatase and specific cell marker genes, and the
      potential of forming embryoids and teratomas. CONCLUSION: A new human embryonic
      stem cell line NJGLLhES1 was successfully established, which remains
      karyotypically and phenotypically stable, undifferentiated and capable of self
      renewal and pluripotential differentiation.

PMID- 19157228
TI  - [Grape seed extract induces morphological changes of prostate cancer PC-3 cells].
AB  - OBJECTIVE: To observe the morphological changes of prostate cancer PC-3 cells
      induced by grape seed extract (GSE). METHODS: PC-3 cells were incubated with
      different concentrations of GSE (100, 200 and 300 microg/ml) for 24, 48 and 72
      hours, and then observed for morphological changes by invert microscopy, HE
      staining and transmission electron microscopy. RESULTS: The incubated PC-3 cells
      appeared round, small, wrinkled and broken under the invert microscope and
      exhibited the classical morphological characteristics of cell death under the
      electron microscope, including cell atrophy, increased vacuoles, crumpled nuclear
      membrane, and chromosome aggregation. CONCLUSION: GSE can cause morphological
      changes and induce necrosis and apoptosis of PC-3 cells.

PMID- 19157229
TI  - [Expression of P-selectin in the penile vascular epithelia of smoking rats].
AB  - OBJECTIVE: To observe the expression of P-selectin in the penile vascular
      epithelial cells and the morphological changes in the ultrastructure of the
      penile cavernous tissues of smoking rats, and to explore the pathogenesis of
      smoking-induced erectile dysfunction. METHODS: Fifty healthy Wistar rats were
      randomly divided into a normal control, a long-term heavy smoking group, a long
      term light smoking, a short-term heavy smoking and a smoking cessation group.
      Their erectile function was tested by subcutaneous injection of apomorphine
      (APO), the P-selectin expression in the penile vascular epithelial cells detected
      by ELISA and the morphological changes in the ultrastructure of the penile
      cavernous tissues observed under the transmission electron microscope (TEM).
      RESULTS: The levels of P-selectin were 10.78 +/- 1.71 ng/L, 62.62 +/- 5.95 ng/L,
      40.06 +/- 3.97 ng/L, 41.37 +/- 4.06 ng/L and 22.80 +/- 3.15 ng/L respectively in
      the normal control, long-term heavy smoking, long-term light smoking, short-term
      heavy smoking and smoking cessation groups, with significant differences between
      the control group and the other four (P < 0.05). Electron microscopy showed
      abnormal arrangement of endothelia, penile cavernous sinuses and smooth muscle
      cells, disrupted continuity of endothelia, damaged ultrastructure of endothelial
      and smooth muscle cells in the penile cavernous tissue, and obvious proliferation
      and fibrosis of interstitial tissues in the smoking rats. CONCLUSION: Smoking
      increases the P-selectin expression in the penile vascular epithelial cells and
      damages the ultrastructure of the penile cavernous tissue, which may be the main
      contributors to smoking-induced erectile dysfunction.

PMID- 19157230
TI  - [AZF microdeletions are not related with recurrent spontaneous abortion].
AB  - OBJECTIVE: To study the relationship between azoospermia factor (AZF)
      microdeletions of the Y-chromosome and recurrent spontaneous abortion. METHODS:
      We collected 26 chorionic villus samples from abortive male embryos and 51 blood
      samples from the husbands whose wives had recurrent spontaneous abortion,
      extracted genomic DNA from the samples and detected 12 STSs in the AZFa, AZFb and
      AZFc regions of Yq11.2 by amplification multiplex PCR. RESULT: AZF microdeletions
      were found neither in the chorionic villus samples nor in the blood samples.
      CONCLUSION: There is no relationship between AZF microdeletions and recurrent
      spontaneous abortion.

PMID- 19157231
TI  - [Volumes of total prostate and transitional zone are positively correlated with
      age in benign prostatic hyperplasia patients].
AB  - OBJECTIVE: To investigate the total prostate volume (TPV) and prostate
      transitional zone volume (TZV) in different age groups of benign prostatic
      hyperplasia patients, calculate the transitional zone index (TZI), and analyze
      correlation of age with the above parameters. METHODS: We divided 1,563 BPH
      patients into 4 age groups (50-59, 60-69, 70-79 and 80-89 y), measured their TPV
      and TZV by rectal ultrasonography, calculated their TZI and evaluated all the
      data obtained by statistical analysis. RESULTS: The TPV, TZV and TZI of the BPH
      patients were shown to be (32.27 +/- 15.76) ml, (9.55 +/- 98) ml and 0.28 +/-
      0.13 in the 50-59 y group; (40.93 +/- 17.45) ml, (14.94 +/- 11.83) ml and 0.34 +/
      0. 16 in the 60-69 y group; (46.56 +/- 20.31) ml, (19.54 +/- 19.25) ml and 0.39
      +/- 0.16 in the 70-79 y group; and (47.85 +/- 26.63) ml, (20.40 +/- 16.78) ml and
      0.41 +/- 0.19 in the 80-89 y group. Both TPV and TZV were positively correlated
      with the patients' age, (r1 = 0.232, r2 = 0.256). CONCLUSION: TPV and TZV
      increase with age in BPH patients, the latter even more obviously than the
      former.

PMID- 19157232
TI  - [Evaluation of CD4+ CD25+ regulatory T cells in the peripheral blood of recurrent
      spontaneous abortion patients].
AB  - OBJECTIVE: To explore the role of CD4+ CD25+ regulatory T cells (CD4+ CD25+ Tr)
      in the pathogenesis of recurrent spontaneous abortion. METHODS: Peripheral blood
      samples were collected from 29 women with unexplainable recurrent spontaneous
      abortion (the URSA group) and another 20 with normal pregnancy (the control
      group). The percentage of CD4+ CD25+ Tr in the peripheral blood was measured by
      flow cytometry. RESULTS: The rate of CD4+ CD25bright Tr in the URSA patients
      ([1.98 +/- 0.96]%) was significantly lower than that in the control group ([3.21
      +/- 1.25]%, P < 0.05), while the percentages of CD4+ CD25+ and CD4+ CD25dim and
      the ratio of CD4+ CD25bright/CD4+ were not significantly different between the
      two groups (P > 0.05). CONCLUSION: URSA might be associated with the decreased
      percentage of CD4+ CD25bright Tr, which plays an important role in fetomaternal
      immunologic tolerance.

PMID- 19157233
TI  - [Effects of isoflurane combined with diltiazem on human sperm motility].
AB  - OBJECTIVE: To observe the effects of isoflurane combined with diltiazem on human
      sperm motility in vitro and to investigate its possible mechanism. METHODS: Ten
      normal semen samples were collected, each divided into 9 groups, one as the
      control and the others treated in vitro with different concentrations of
      diltiazem or diltiazem +4.2% isoflurane for 1 hour. Sperm motility was observed
      with the computer-assisted sperm analyzer. RESULTS: Compared with the control,
      diltiazem significantly decreased sperm motility at the concentrations of 0.01
      g/L, 0.04 g/L, 0.2 g/L and 1 g/L in a dose-dependent manner, and reduced it to
      approximately 0% at 1 g/L. When combined with 4.2% isoflurane, diltiazem
      obviously increased sperm motility at 0.01 g/L, markedly decreased it at 0.2 g/L,
      and effected no significant difference at 0.04 g/L and 1 g/L as compared with the
      corresponding concentrations of diltiazem alone. CONCLUSION: The stimulating
      effect of isoflurane on sperm motility may be associated with the calcium ion
      channel in sperm. When completely blocked by diltiazem, this effect may turn into
      an inhibition of sperm motility.

PMID- 19157234
TI  - [Determination of plasma homocysteine in oligospermia and/or asthenospermia
      patients].
AB  - OBJECTIVE: To detect the level of fasting plasma homocysteine (Hcy) in patients
      with oligospermia and/or asthenospermia and to investigate its clinical
      significance. METHODS: Semen quality analyses and fasting plasma Hcy
      determination were performed for 86 infertility patients (21 with oligospermia,
      32 with asthenospermia and 33 with oligo-asthenospermia) and 19 normal fertile
      volunteers. The results were compared. RESULTS: The level of plasma Hcy was
      significantly higher in the infertility patients than in the normal controls (P <
      0.05) and negatively correlated with sperm concentration (r = -0.433, P < 0.01),
      the percentage of grade a sperm (r = -0.303, P < 0.05) and the percentage of
      grade a+b sperm (r = -0.339, P < 0.01). CONCLUSION: The increased level of human
      plasma Hcy directly or indirectly affects spermatogenesis and correlates
      negatively with oligospermia and/or asthenospermia.

PMID- 19157235
TI  - [Clinical significance of electrophysiological tests of BCR, ICR and PSEP for ED
      patients].
AB  - OBJECTIVE: To assess the clinical significance of electrophysiological tests of
      bulbocavernosus reflex (BCR), ischiocavernosus reflex (ICR) and pudenda
      somatosensory evoked potential (PSEP) for patients with erectile dysfunction
      (ED). METHODS: Electrophysiological tests of BCR, ICR and PSEP were performed for
      232 ED patients with IIEF-5 scores of 2-20 (10.39 +/- 5.52), another 21 normal
      volunteer controls underwent the same tests, and the results were compared.
      RESULTS: Abnormal results, such as prolonged and advanced latencies, were found
      in 94 (40.5%) of the patients, which suggested neurotic ED with different degrees
      of cauda equine nerve injuries. CONCLUSION: Electrophysiological tests of BCR,
      ICR and PSEP can objectively reveal the functional state of the cauda equine
      nerve and offer an important support to the diagnosis of nerve-mediated ED.

PMID- 19157236
TI  - [Transperitoneal laparoscopic modified lymph node dissection for clinical stage I
      nonseminomatous germ cell testicular carcinoma].
AB  - OBJECTIVE: To evaluate the feasibility and short-term clinical effect of
      transperitoneal laparoscopic modified retroperitoneal lymph node dissection
      (LmRPLND) in the management of clinical Stage I nonseminomatous germ cell
      testicular tumors. METHODS: From October 2004 to July 2006, 7 patients aged 26-36
      (mean 30) years underwent LmRPLND with modified unilateral template dissection
      for clinical Stage I nonseminomatous germ cell testicular tumors, which were 3.0
      cm x 2.5 cm x 2.0 cm to 6.5 cm x 4.5 cm x 3.0 cm in size, 3 cases on the left and
      4 on the right, all diagnosed by ultrasound, computerized tomography (CT) and
      chest X-ray and confirmed by biopsy following radical orchiectomy. Those with
      positive lymph nodes received 3 courses of chemotherapy. RESULTS: Success was
      achieved in all the 7 cases, the operative time ranging from 120 to 210 min (mean
      160 min), blood loss from 50 to 200 ml (mean 150 ml), and with no blood
      transfusion. The drainage tubes were removed 1-2 days after surgery. The mean
      postoperative hospital stay was 5.5 days. The follow-up lasted 6-32 (mean 14)
      months, which revealed normal erection and ejaculation in all the patients, but
      no major postoperative complications. Pathologically, lymph nodes were negative
      in 6 cases and positive (1/18) in 1. Normal results were obtained in HCG and AFP
      tests as well as in retroperitoneal ultrasound and chest X-ray examinations. The
      patient with positive lymph nodes was treated by adjuvant chemotherapy for 3
      courses and found free of malignancy during a 6-month follow-up. CONCLUSION:
      LmRPLND is a safe and minimally invasive treatment option for patients with
      clinical Stage I nonseminomatous germ cell testicular carcinoma. With fewer
      complications and faster recovery, it appears to be a desirable substitute for
      the open procedure.

PMID- 19157237
TI  - [Questionnaires on the diagnosis and treatment of erectile dysfunction].
AB  - Patient-centered questionnaires, as widely used tools for the diagnosis of
      erectile dysfunction (ED) and the assessment of ED treatment efficacy, are
      increasing in number and kinds. This review focuses on a few effective and most
      commonly used ED-related questionnaires, including the International Index of
      Erectile Function (IIEF), Sexual Health Inventory for Men (SHIM), Erectile
      Function Domain of the IIEF (IIEF-EF), Erection Hardness Grading Scale (EHGS),
      Self-Esteem and Relationship Questionnaire (SEAR), Erection Dysfunction Inventory
      of Treatment Satisfaction (EDITS), Quality of Erection Questionnaire (QEQ),
      Treatment Satisfaction Scale (TSS), Psychological and Interpersonal Relationship
      Scales (PAIRS), and Sexual Experience Questionnaire (SEX-Q). The objectives,
      contents and characteristics of these questionnaires are explained and discussed.

PMID- 19157238
TI  - [Cell apoptosis and male erectile dysfunction].
AB  - Erectile dysfunction (ED) is a common disease in men, especially in old men, the
      mechanisms of which have yet to be further investigated. Accumulating evidence
      indicates that one important mechanism of ED is the excessive apoptosis of
      erectile tissues, which can be caused by a lot of risk factors of ED and thereby
      reduce penile erectile function. This paper reviews the mechanisms of cell
      apoptosis, the role of apoptosis in ED, the relationship between apoptosis and
      the risk factors of ED, such as diabetes mellitus, hyperlipidemia, cavernous
      nerve injury and aging.

PMID- 19157239
TI  - [Advances in the treatment of chronic prostatitis/chronic pelvic pain syndrome].
AB  - So far the etiology of chronic prostatitis (PC) and particularly chronic pelvic
      pain syndrome (CPPS) remains to be elucidated. According to recent epidemiologic
      data, CP is the most common urological disease in men below 50 years and occurs
      in 2.5%-16.0% of the world population. Since the 1990s, researchers of many
      countries have carried out deeper, more extensive and larger scaled studies than
      ever before on the etiology, diagnosis and treatment of the disease, with the
      sponsorship and coordination of such international institutions as the
      International Prostatitis Collaborative Network (IPCN), the Chronic Prostatitis
      Collaborative Research Network of the National Institute of Health (NIH-CPCRN)
      and so on. As prevalent as multiple sclerosis, CPPS is the most common yet most
      poorly understood "prostatitis syndrome". This article reviews the progress in
      the studies of the treatment of CPPS, explores the main problems and ventures the
      prospects for the development in this field.

PMID- 19157240
TI  - [Xianling Gubao Capsule improves semen quality].
AB  - OBJECTIVE: To observe the effect of the compound Chinese traditional drug
      Xianling Gubao Capsule on the semen quality of infertile males. METHODS: We
      treated 66 infertile men with Xianling Gubao Capsule for 24 months, and analyzed
      the semen quality and sperm morphology before and after the treatment. RESULTS:
      Two months after the medication, sperm concentration was increased by a small
      margin, but no statistically significant changes were observed in sperm vitality
      and motility (P > 0.05), the rate of morphologically normal sperm was
      significantly raised from 25.8% before treatment to 57.6% (P < 0.05) in those
      with the normal rate > or = 15%, but decreased from 53.0% to 25.8% (P < 0.05) in
      those with the normal rate < 9%. Among the 7 cases of oligospermia, the rate of
      morphologically normal sperm was elevated to an average of 10.9% after the 4
      month medication, significantly different from the baseline rate of 5.8% (P <
      0.05). Five spontaneous pregnancies and 1 successful IVF-ICSI were achieved
      during the treatment. CONCLUSION: Xianling Gubao Capsule can improve semen
      quality and significantly increase the percentage of morphologically normal
      sperm.

PMID- 19157241
TI  - Prevalence and awareness of hypertension in an urban township of South Africa:
      compelling need for action.

PMID- 19157242
TI  - The impact of acculturation on Latinos' perceived barriers to HIV primary care.
AB  - US Latino adults are disproportionately affected by the HIV epidemic and
      experience disparities in access to HIV care. However, relatively little is known
      about how acculturation affects perceived barriers to engagement in care among
      Latinos. This article examines factors that may be associated with engaging HIV
      infected persons in primary care by using interview data from 651 Latino and non
      Latino adults presenting for services at five agencies that participated in a
      multisite demonstration project Latinos (n=219) were more likely than non-Latino
      Whites (n=117) to be male, recently diagnosed with HIV, less educated, without
      health insurance, not on Medicaid, taking HIV medications, and in better physical
      health. In addition, Latinos were more likely to report facing numerous
      structural barriers, stigma-related worries/concerns, and belief barriers than
      were non-Latino Whites. Upon closer examination of the Latino subsample,
      acculturation (based on language) was associated with reported structural
      barriers, worry/concern barriers, and belief barriers. In the final multivariate
      model that controlled for site, Spanish language was significantly associated
      with experiencing stigma-related worries/concerns that impact HIV status.

PMID- 19157243
TI  - Regional differences in the prevalence, treatment and control of hypertension and
      dyslipidemia in US urban Hispanic populations participating in health screening
      events.
AB  - OBJECTIVE: We examine the prevalence, treatment, and control of hypertension,
      dyslipidemia, and concomitant hypertension and dyslipidemia among Hispanics in
      four US communities. METHODS: This was a cross-sectional study of Hispanics who
      participated in health screening programs from 2004 to 2006. We enrolled 5288
      Hispanics in Miami (n=372), New York (n=254), Los Angeles (n=4037), and Houston
      (n=625). The main outcome measures were prevalence, treatment and control rates
      of hypertension, dyslipidemia, and concomitant hypertension and dyslipidemia.
      RESULTS: Overall prevalence rates of hypertension, dyslipidemia, and concomitant
      hypertension and dyslipidemia were 37.5%, 26.6%, and 15.3%, respectively.
      Hypertension treatment rates ranged from 30.9% (Houston) to 68.2% (Miami)
      (P<.05); control was achieved in 34.7% (Los Angeles) to 47.8% (New York, P<.05).
      Dyslipidemia treatment rates were lowest in Houston (36.5%) and highest in New
      York (75.3%, P<.05); control rates were 62.3% (Houston) to 75.1% (Los Angeles
      P<.05). Dual treatment of hypertension/dyslipidemia ranged from 24.4% (Houston)
      to 69.4% (New York, P<.05), dual control was achieved in 4.5% (Houston) to 35.3%
      (New York, P<.05). Multivariable logistic regression analyses showed the odds of
      having each condition did not to differ by region, but regional differences
      existed for treatment and control. CONCLUSIONS: A high prevalence of
      hypertension, dyslipidemia, and combined hypertension and dyslipidemia and low
      control rates for hypertension and concomitant hypertension and dyslipidemia
      exist among US Hispanic adults in different communities.

PMID- 19157244
TI  - Self-reported and measured height and weight: impact on racial/ethnic differences
      in hypertension.
AB  - OBJECTIVE: We compare estimability of obesity from self-reported and measured
      height and weight in White, Black, and Hispanic Americans. We also sought to
      determine the effect of using self-reported and measured height and weight in
      determining the association of obesity with risk of hypertension in these
      population groups. METHODS: The 1999-2000 National Health and Nutrition
      Examination Survey (NHANES 1999-2000) participants' (n=4789) self-reported and
      measured height and weight were used for this study. Logistic regression adjusted
      for age, blood glucose level, total cholesterol level, smoking status, and
      exercise status to compare the association of obesity estimated from self
      reported and measured height and weight on the prevalence odds of hypertension.
      RESULTS: Men tended to overestimate height and weight, and women tended to
      overestimate height and underestimate weight. Using self-reported values
      diminished the prevalence of obesity and odds of hypertension, and this effect
      related to ethnicity and sex. In men, self-report decreased the prevalence of
      hypertension by 9.1%, 11.8%, and 26.6% in Whites, Blacks, and Hispanics,
      respectively. The analogous values in women were 11.1%, 22.7%, and 7.7%.
      CONCLUSION: Public health researchers and practitioners who use self-reported
      height and weight should be aware of the potential for error when using self
      reported values to estimate obesity so that they may make better decisions
      regarding obesity screening and prevention.

PMID- 19157245
TI  - Objectively measured physical activity and cardiovascular disease risk factors in
      African American girls.
AB  - OBJECTIVE: This study examines the associations between objectively measured
      physical activity and cardiovascular disease (CVD) risk factors in preadolescent
      African American girls. METHODS: We conducted a cross-sectional analysis of data
      from Stanford Girls Health Enrichment Multisite Studies (GEMS) trial. Physical
      activity was assessed for four days by using an ActiGraph accelerometer and was
      correlated with anthropometric measures, blood pressure, blood lipids, glucose,
      and insulin. Associations between physical activity and CVD risk factors were
      computed using by Spearman correlations. Bonferroni adjustment alpha = .003 was
      used to correct for multiple testing. RESULTS: A total of 261 girls participated,
      of which 208 had complete CVD risk measures (mean age 9.4 years, mean body mass
      index 20.7 kg/m2). Average daily physical activity and time spent in moderate-to
      vigorous physical activity (MVPA) were significantly correlated with body mass
      index (r = -.23, P=.0008 and r = -.29, P<.0001, respectively) and insulin (r = 
      .27, P=.0001 and r = -.30, P<.0001, respectively) but not to other CVD factors.
      After adjusting for age-adjusted pubertal stage of development, the association
      between MVPA and insulin remained significant. CONCLUSIONS: Objective measures of
      both average daily physical activity and MVPA were inversely associated with body
      mass index and insulin levels in African American girls.

PMID- 19157246
TI  - A comparison of cardiovascular disease risk factor biomarkers in African
      Americans and Yoruba Nigerians.
AB  - OBJECTIVE: Classical risk factors for coronary artery disease are changing in the
      developing world while rates of cardiovascular disease are increasing in these
      populations. Newer risk factors have been identified for cardiovascular disease,
      but these have been rarely examined in elderly populations and not those of
      developing countries. METHODS: This study was a cross-sectional comparison from a
      longitudinal, observational, epidemiologic study in which participants are
      interviewed at three-year intervals. The sample included 1510 African Americans
      from Indianapolis, Indiana, and 1254 Yoruba from Ibadan, Nigeria. We compared
      anthropomorphic measurements; biomarkers of endothelial dysfunction (plasminogen
      activator inhibitor type 1 [PAI-1 and E-selectin), inflammation (C-reactive
      protein), and lipid oxidation (8-isoprostane); and levels of lipids,
      homocysteine, folate, and vitamin B12. RESULTS: Cholesterol, triglycerides, and
      low-density lipoprotein cholesterol levels were higher in African Americans. For
      markers of endothelial dysfunction, E-selectin and homocysteine differed between
      men, and PAI-1 was higher in the Yoruba. C-reactive protein differed only in
      women, but 8-isoprostane was higher in the Yoruba. CONCLUSION: Higher lipid
      levels in African Americans are consistent with their Western diet and lifestyle.
      Oxidative stress appears to be higher in the Yoruba than in African Americans,
      which may be secondary to dietary differences. Whether these differences in
      classical and emerging risk factors account for the different rates of
      cardiovascular disease, dementia, or other morbidities in these two populations
      remains to be determined.

PMID- 19157247
TI  - Prevalence of the metabolic syndrome in San Juan, Puerto Rico.
AB  - OBJECTIVE: The metabolic syndrome is associated with a high risk of diabetes and
      cardiovascular disease, and Hispanics in the United States have higher rates than
      do other ethnic groups. We assessed the prevalence of the metabolic syndrome and
      its individual components in Puerto Rican adults. METHODS: We conducted a cross
      sectional study that used a probability cluster design to select a sample of
      households of the San Juan metropolitan area from 2005 through 2007. A total of
      859 persons aged 21-79 years completed a face-to-face interview, blood pressure
      and waist circumference measurements, and blood sampling. Our primary outcome
      measure was metabolic syndrome as defined by the updated NCEP-ATP criteria.
      RESULTS: Prevalence of the metabolic syndrome was 43.3%; 45.3% for men and 42.2%
      for women (P>.05). Prevalence significantly rose with age, from 12.8% among
      participants aged 21-29 years to 58.2% for participants aged 70-79 years
      (P<.001). Corresponding increases in the prevalence of the metabolic syndrome in
      both men and women were also observed; the prevalence peaked in men aged 50-59
      years (62.6%) and in women aged 70-79 years (65.2%). Elevated glucose (49.8%) and
      abdominal obesity (49.0%) were the most common components of the metabolic
      syndrome, followed by elevated blood pressure (46.1%), reduced high-density
      lipoprotein cholesterol (46.0%), and elevated triglycerides (31.3%). Substantial
      variations were found between men and women in the prevalence of individual
      components. CONCLUSIONS: Puerto Ricans have a high prevalence of the metabolic
      syndrome. This health disparity has implications for diabetes and cardiovascular
      prevention programs.

PMID- 19157248
TI  - Racial/ethnic disparities in mortality related to congenital heart defects among
      children and adults in the United States.
AB  - BACKGROUND: Congenital heart defects (CHD) are the most common birth defect and
      are a major cause of childhood illness and death. Recent progress in management
      of persons with CHD may have decreased CHD-related mortality. METHODS: Year 2000
      US death records were used to determine CHD-related mortality by age, sex, and
      race/ethnicity in children and adults. CHD-related mortality was defined as all
      deaths with any mention of CHD on the death certificate. Age-, sex-, and
      racial/ethnic-specific population counts were obtained from the 2000 US Census
      and used as denominators in mortality rates. RESULTS: In 2000 there were 5441
      (.23%) CHD-related deaths and CHDs were mentioned 6121 times as the underlying or
      contributing cause of death. In 68.4% of CHD-related deaths, CHD was the
      underlying cause of death. Non-Hispanic Black males had greater risk of CHD
      related death than did non-Hispanic White males (RR 1.25, 95% CI 1.08-1.45). Both
      Hispanic males and females had lower rates of CHD-related deaths than did non
      Hispanic Whites (RR .72, 95% CI .60-.85; RR .52, 95% CI .42-.65, respectively).
      "Unspecified congenital malformation of the heart" was the most common cause of
      death overall; however, "malformation of the coronary vessels" was most often a
      cause of death for non-Hispanic Blacks and children aged 10-19 years.
      CONCLUSIONS: Racial/ethnic differences in CHD-related mortality exist in the
      United States. Management of CHD, access to adequate care, and misclassification
      in cause of death reporting on death records may explain the observed
      differences.

PMID- 19157249
TI  - Association between selected unhealthy lifestyle factors, body mass index, and
      chronic health conditions among individuals 50 years of age or older, by
      race/ethnicity.
AB  - OBJECTIVE: To examine the association between selected unhealthy lifestyle
      factors, body mass index (BMI), and chronic conditions among individuals 50 years
      of age or older, by race/ethnicity. DESIGN: We analyzed 2001-2004 data from the
      Behavioral Risk Factor Surveillance System (BRFSS), a state-based system of
      annual random-digit-dialed telephone surveys. PARTICIPANTS: Noninstitutionalized
      US adults aged 50 years or older with landline telephones. RESULTS: Of 442,167
      BRFSS respondents who met our study criteria, 81.6% were non-Hispanic (NH) White,
      8.4% were NH Black, 1.6% were NH Asian, 1.0% were NH American Indian, and 7.4%
      were Hispanic. Within each racial/ethnic group, weight status as measured by BMI
      was strongly associated with all five health conditions examined and particularly
      with diabetes, hypertension, and doctor-diagnosed arthritis. Among NH Whites and
      NH Blacks, those who were overweight or obese were significantly more likely than
      those of normal weight to have diabetes (NH Whites: adjusted odds ratio [AOR] =
      1.94 and 5.25, respectively; NH Blacks: AOR = 1.87 and 3.36, respectively). Among
      obese NH Asians, NH American Indians, and Hispanics, the AORs for diabetes were
      3.97, 4.15, and 2.67, respectively. The AORs for hypertension among those who
      were overweight and obese, respectively, were 1.78 and 3.47 among NH Whites; 1.65
      and 2.98 among NH Blacks, 1.91 and 7.14 among NH Asians, 2.00 and 2.65 among NH
      American Indians, and 1.48 and 3.20 among Hispanics. CONCLUSIONS: Our study
      revealed a strong association between BMI and risk for chronic health conditions
      among individuals 50 years of age or older in all racial/ethnic categories. It is
      important to use messages that are culturally appropriate when planning or
      conducting health promotion campaigns for selected ethnic/racial groups. In
      addition, careful research to document health status and healthcare needs within
      each major ethnic group is needed.

PMID- 19157250
TI  - Cardiovascular disease prevalence, associated risk factors, and plasma
      adiponectin levels among Filipino American women.
AB  - OBJECTIVES: This cross-sectional study was designed to examine the association
      between adiponectin and cardiovascular disease (CVD) among an understudied ethnic
      group of Filipino American women. METHODS: We recruited 266 Filipino women aged
      40-86 years from the University of California, San Diego Filipino Women's Health
      Study (1995-1999). Plasma adiponectin was extracted from archive blood samples
      and measured by radioimmunoassay. CVD was defined as coronary heart disease,
      angina, myocardial infarction, or stroke by history, electrocardiogram (Minnesota
      coding), or Rose questionnaire. RESULTS: CVD prevalence among Filipinas was 20.7%
      (n=55), of which 85.5% were newly diagnosed. Filipinas with versus without CVD
      had more antihypertensive medication use (44.4% vs 26.7%), more parental history
      of myocardial infarction (38.2% vs 21.8%), higher proinsulin levels (13.2 vs 11.0
      pmol/L), lower adiponectin levels (5.09 vs 6.15 microg/mL), and higher
      prevalences of the metabolic syndrome (34.6% vs 28.0%) and microalbuminuria
      (24.0% vs 12.2%). Adiponectin (adjusted OR .46, 95% CI .23-.89, P=.021) was
      independently associated with CVD in multivariate analysis that adjusted for age,
      exercise, family history, diabetes, hypertension, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol and microalbuminuria.
      CONCLUSIONS: Independent of known risk factors, adiponectin was associated with
      CVD among Filipinas. This finding suggests that adiponectin may be a useful CVD
      indicator among this ethnic population.

PMID- 19157251
TI  - Factors associated with self-reported depression in Arab, Chaldean, and African
      Americans.
AB  - BACKGROUND: Although depression is a chronic illness with high morbidity and
      personal and economic losses, little is known about depression in immigrants with
      an Arab or Chaldean ethnic background. OBJECTIVES: Our primary objective was to
      determine the overall and ethnicity-specific prevalence of self-reported
      depression in Arab Americans, Chaldean Americans, and African Americans in the
      Midwest. The secondary objective was to evaluate the associations between
      potential risk and protective factors and the presence of self-reported
      depression. METHOD: A total of 3543 adults were recruited from the Arab and
      Chaldean communities in Metropolitan Detroit. The sample in this study was
      restricted to those of Arab, Chaldean, and African ethnic backgrounds, resulting
      in 81.2% of the original sample (n=2878). A health assessment survey
      questionnaire was administered. RESULTS: The overall rate of self-reported
      depression was 18.2%. The highest rate of depression was found in Arab American
      participants (23.2%), followed by African Americans (15%) and Chaldeans (13.3%).
      Self-reported prevalence of depression by country of origin differed
      significantly. CONCLUSIONS: Our results show the need to provide culturally
      competent mental health services for Arab Americans and other minority American
      subgroups. Research is needed to identify risk factors, preferably modifiable
      factors, and to ascertain which factors are similar and non-similar to the
      general American population.

PMID- 19157252
TI  - Patterns of relationships between cardiovascular disease risk factors and
      neurocognitive function in African Americans.
AB  - OBJECTIVE: The association between cardiovascular disease (CVD) risk and
      neurocognitive function has gathered a good deal of attention in the health and
      social science literature; however, the relationship among several CVD risk
      factors and neurocognitive function has not been fully explored in an African
      American sample. The purpose of this study was to examine the pattern of
      relationships among four CVD risk factors and five measures of higher cortical
      functions. METHODS: Data were collected from a sample of 106 African American
      community-dwelling adults in the metropolitan Washington, DC, area. A nurse
      collected blood pressure, waist circumference, and a blood sample (to assess
      triglycerides and high-density lipoprotein (HDL) cholesterol) from study
      participants. Participants completed the Symbol Digit Modalities Test,
      Trailmaking B, Stroop Color-word Task, California Verbal Learning Test-II, and
      Wisconsin Card Sorting Test as assessments of neurocognitive function. Canonical
      analysis and multiple regression analysis were the major statistical methods
      utilized to assess relationships between CVD risk factors and neurocognitive
      function. RESULTS: The results suggest that 1) attentional processes are
      associated with diastolic blood pressure levels, 2) verbal learning processes are
      associated with diastolic blood pressure and triglyceride levels, and 3) the
      ability to shift cognitive set is associated with HDL cholesterol levels.
      CONCLUSION: As cardiovascular health worsens in our society, particularly among
      ethnic minorities, the neurocognitive consequences must be clearly understood.
      Future studies should focus on identifying and building awareness of
      cardiovascular and neurocognitive links through longitudinal research designs and
      brain imaging technology.

PMID- 19157253
TI  - Characteristics of American Indian and Alaska native adult caregivers, Behavioral
      Risk Factor Surveillance System, 2000.
AB  - OBJECTIVES: We compared characteristics of American Indian and Alaska Native
      (AI/AN) adult caregivers (age > or = 18 years) who were caring for an older adult
      (age > or = 60 years) to those of other ethnic groups. METHODS: Participants
      (N=20,996) were from the 2000 Behavioral Risk Factor Surveillance System.
      Caregivers provided regular care or assistance during the past month to a family
      member or friend who was > or = 60 years of age. In addition, participants were
      asked to indicate whom they would call to arrange short- or long-term care in the
      home for elderly relatives or friends who were no longer able to care for
      themselves. RESULTS: A total of 16.4% of adults were caregivers to a person who
      was > or = 60. AI/AN were significantly more likely to report being caregivers
      than were people who were of Asian descent. Compared to AI/AN caregivers,
      Hispanic caregivers indicated that if a friend or relative needed short- or long
      term care, they were more likely to provide care themselves (29.1% vs 46.6%) and
      that they were less likely to indicate that they would contact a professional
      resource (14.5% vs 25.2%). CONCLUSIONS: Family caregivers provide a valuable
      service in the United States, particularly to chronically ill or disabled older
      adults. National, state, and local surveys should regularly collect information
      on caregiving.

PMID- 19157254
TI  - Health-related quality of life among minority populations in the United States,
      BRFSS 2001-2002.
AB  - OBJECTIVE: Improving quality of life is one of the goals of the Healthy People
      2010 objectives. Health-related quality of life (HRQOL) measures can be used to
      indicate unmet health needs and identify health disparity in population
      subgroups. SETTING AND PARTICIPANTS: Data were gathered from the 2001-2002
      Behavioral Risk Factor Surveillance System (BRFSS), a state based annual random
      digit-dialed telephone survey of non-institutional adults aged > or = 18 years.
      METHODS: The 4-items Healthy Days questions and the 5-item Health Days Symptoms
      questions were compared among non-Hispanic Whites (White), non-Hispanic Blacks
      (Black), non-Hispanic Asians (Asian), non-Hispanic American Indian or Alaska
      Native (AIAN) and Hispanics. Logistic regression models were constructed to
      evaluate racial/ethnic differences in HRQOL measures after adjusting for
      confounding factors. RESULTS: After adjusting for confounders, Blacks were 40%,
      AIANs were 80%, and Hispanics were twice as likely to report fair or poor general
      health than Whites. Asians were less likely and AIANs were more likely to report
      frequent physical distress, mental distress, and activity limitations. After
      controlling for confounders, there were no racial or ethnic differences in the
      prevalence of frequent depressive symptoms; however, Blacks, Hispanics, and
      Asians were less likely to report frequent pain, frequent anxiety symptom, and
      frequent sleep insufficiency than Whites. Blacks, Asians, and AIANs were equally
      likely to report infrequent vitality as Whites. CONCLUSIONS: Mental health status
      has a larger impact on health in certain race/ethnic groups. More public health
      efforts should address the mental health needs of Blacks, Hispanics, and AIANs.

PMID- 19157255
TI  - Black newspapers as a tool for cancer education in African American communities.
AB  - BACKGROUND: Despite the long history, wide reach and unique influence of Black
      newspapers in many African American communities, no national studies have
      examined how these newspapers cover health and cancer issues, or reader
      perceptions of their coverage. DESIGN AND PARTICIPANTS: A two-year national
      sample of Black newspapers (n=24) and community-matched general audience
      newspapers (n=12) was reviewed, and 8,690 health and cancer stories were
      identified and content analyzed. A survey of 783 Black newspaper readers in the
      same 24 communities assessed reading frequency and perceptions of reporting for
      both types of newspapers, as well as readers' health concerns and cancer
      screening behaviors. RESULTS: As a proportion of total health coverage, Black
      newspapers published more cancer stories than general audience newspapers, and
      their stories were more likely to contain localized information, address
      disparities, focus on prevention, include calls to action for readers and refer
      readers to cancer information resources (all P<.001). Black newspaper readers
      identified cancer as the health issue that concerned them most, yet rated it the
      fourth most important health problem affecting African Americans. CONCLUSIONS:
      Black newspapers hold promise for helping to eliminate cancer disparities by
      increasing cancer awareness, prevention, and screening among African Americans.

PMID- 19157256
TI  - Using "socially assigned race" to probe white advantages in health status.
AB  - OBJECTIVES: We explore the relationships between socially assigned race ("How do
      other people usually classify you in this country?"), self-identified
      race/ethnicity, and excellent or very good general health status. We then take
      advantage of subgroups which are discordant on self-identified race/ethnicity and
      socially assigned race to examine whether being classified by others as White
      conveys an advantage in health status, even for those who do not self-identify as
      White. METHODS: Analyses were conducted using pooled data from the eight states
      that used the Reactions to Race module of the 2004 Behavioral Risk Factor
      Surveillance System. RESULTS: The agreement of socially assigned race with self
      identified race/ethnicity varied across the racial/ethnic groups currently
      defined by the United States government. Included among those usually classified
      by others as White were 26.8% of those who self-identified as Hispanic, 47.6% of
      those who self-identified as American Indian, and 59.5% of those who self
      identified with More than one race. Among those who self-identified as Hispanic,
      the age-, education-, and language-adjusted proportion reporting excellent or
      very good health was 8.7 percentage points higher for those socially assigned as
      White than for those socially assigned as Hispanic (P=.04); among those who self
      identified as American Indian, that proportion was 15.4 percentage points higher
      for those socially assigned as White than for those socially assigned as American
      Indian (P=.05); and among those who self-identified with More than one race, that
      proportion was 23.6 percentage points higher for those socially assigned as White
      than for those socially assigned as Black (P<.01). On the other hand, no
      significant differences were found between those socially assigned as White who
      self-identified as White and those socially assigned as White who self-identified
      as Hispanic, as American Indian, or with More than one race. CONCLUSIONS: Being
      classified by others as White is associated with large and statistically
      significant advantages in health status, no matter how one self-identifies.

PMID- 19157257
TI  - Prevalence, detection, management, and control of hypertension in Ghanaian civil
      servants.
AB  - OBJECTIVES: The goal of this study was to determine the prevalence of
      hypertension and establish the levels of detection, treatment, and control among
      urban civil servants in Ghana. METHODS: A cross-sectional study was conducted on
      1015 urban civil servants aged > or = 25 years from seven randomly selected
      central government ministries in Accra, Ghana. Hypertension was diagnosed when
      the mean of a second and third blood pressure reading was > or = 140/90 mm Hg or
      participants reported that they used antihypertensive medication. RESULTS: The
      age-adjusted (world standard population) prevalence of hypertension was 27.4%
      (95% CI 24.7%-30.1%). The prevalence of hypertension increased with age. The
      proportion of hypertensive participants with severe hypertension (blood pressure
      > or = 180/ 110mm Hg) was 19.2%. Among the 307 participants with hypertension,
      54.1% had been previously detected, 31.3% were on treatment, and 12.7% had their
      blood pressure controlled (< 140/90 mm Hg). Female sex was independently
      associated with higher detection and treatment of hypertension and better
      control. Hypertension was positively associated with age and body mass index and
      negatively associated with physical activity. CONCLUSIONS: The high prevalence of
      hypertension in this population with considerable underdiagnosis and low levels
      of treatment and control is of great concern. It is important to introduce health
      education measures that will promote prevention and early detection of
      hypertension and encourage better compliance to treatment. The reasons for
      inadequate control must be investigated to enable implementation of appropriate
      measures to improve control and reduce the risk of developing complications.
      There is a need to encourage healthier lifestyles with emphasis on preventing
      obesity and increasing level of activity.

PMID- 19157258
TI  - Blood pressure and cardiovascular risk profiles of Africans who migrate to a
      Western country.
AB  - OBJECTIVES: Africans who live in Western countries have a higher prevalence of
      hypertension and other cardiovascular risk factors than do age-matched Africans
      who live in Africa. We conducted a community survey to evaluate cardiovascular
      risk in Africans who recently migrated to Italy. METHODS: Participants (N=83)
      from sub-Saharan Africa were recruited from an outpatient clinic for immigrants.
      Information on immigration date, family history of cardiovascular disease,
      physical activity, and smoking was obtained for all participants. Anthropometric
      parameters, blood pressure measurements, and laboratory analyses--including lipid
      profiles, plasma glucose, renal function, and serum and urinary electrolytes-
      were performed. RESULTS: Although participants who had recently arrived in Italy
      had a low cardiovascular risk, the correlations were significant between the
      length of time in Italy and body weight (r=.47, P<.001), body mass index (r=.59,
      P<.0001), waist circumference (r=.54, P<.0001), total cholesterol (r=.41,
      P<.001), low-density lipoprotein cholesterol (r=.46, P<.0001), systolic blood
      pressure (r=.31, P<.01), and diastolic blood pressure (r=.23, P<.05). The rise in
      systolic and diastolic blood pressure was positively correlated with body weight,
      body mass index, and waist circumference (P<.05 for all) and inversely correlated
      with 24-hour urinary potassium (systolic blood pressure, r=-.35, P<.01; diastolic
      blood pressure, r=-.42, P<.0001). CONCLUSIONS: The length of residence in Italy
      is associated with progressive modifications in cardiovascular risk even in a
      relatively short period of time. The inverse correlation between blood pressure
      and urinary potassium may reflect dietary changes, with a possible reduction in
      fruit and vegetable consumption compared with their original diet.

PMID- 19157259
TI  - Poor diet, little exercise, smoking: Western ways that promote heart disease.

PMID- 19157260
TI  - American Indian and Alaska native families caring for their older family members.

PMID- 19157261
TI  - The metabolic syndrome in Puerto Rico.

PMID- 19157262
TI  - High blood pressure in urban Ghana.

PMID- 19157263
TI  - Read the newspaper for health information.

PMID- 19157264
TI  - Low levels of adiponectin linked to heart disease.

PMID- 19157265
TI  - An immunological approach to cerebral ischemia (I). Immune cells and adhesion
      molecules.
AB  - Ischemic stoke is a major cause of death and an important source of disability in
      industrialized countries. Since there is no ideal treatment for cerebral
      ischemia, any approach aiming to limit the devastating consequences of the
      ischemic process is justified. Concerning immune responses, it has become clear
      in the latest years that actors of the immune system are involved in multiple and
      various neurobiological processes such as cerebral ischemia, neurodegeneration,
      neuroprotection and neuroregeneration. An immunological approach to cerebral
      ischemia can distinguish, besides the implication of inflammation in the
      developing of atherothrombosis thus leading to stroke, the clear involvement of
      immune cells and mediators in processes continuing the initial stage of ischemia,
      having consequences on recovery or lesion extent. Cerebral infarctions develop
      within minutes to hours of cessation of the cerebral blood flow, but may expand
      over subsequent days. There is increasing evidence that leukocytes, cytokines,
      cell adhesion molecules, and other immune mediators contribute to secondary
      infarction growth, but inflammatory cytokines are also involved in signaling
      pathways leading to neuroprotection related to ischemic pre-conditioning. The aim
      of this review is to show some aspects concerning the complex and diverse
      functions of immune modifications occurring in cerebral ischemia. This first part
      will focus on the involvement of immune cells, adhesion molecules and
      immunological transcription factors in the development of ischemic lesion.

PMID- 19157266
TI  - An update on the platelet dysfunction in chronic myeloproliferative syndromes.
AB  - The thrombotic and hemorrhagic diathesis represents a frequent complication in
      myeloproliferative disorders (CMPD). They are correlated with the number of
      platelets, but also with their qualitative disorders, such as membrane
      glycoprotein changes. The latter are revealed by many platelet essays including
      flow-cytometry and include modified activation, secretion and aggregation
      patterns. The thrombopoietin platelet receptor (cMPL), affected by the JAK2 V617
      mutation encountered in CMPD, may be associated with a prothrombotic status. Its
      implication reveals the importance of the molecular genetics profile in defining
      molecular diagnostic hallmarks and makes it a candidate in the early diagnosis of
      myeloproliferative disorder and a predictor of thrombotic complications in this
      group of diseases.

PMID- 19157267
TI  - Physical training--beyond increasing exercise capacity.
AB  - Physical training has traditionally represented the main method used in
      cardiovascular rehabilitation of ischemic patients in the past years. Nowadays,
      cardiovascular rehabilitation has been extended to other cardiovascular diseases,
      such as heart failure. Also, cardiovascular rehabilitation included
      psychological, social and professional measures along with secondary prevention
      methods such as lifestyle changes. It has also been found that physical training
      has other additional effects which increased exercise tolerance. Effects on the
      risk factors regard beneficial effect on body weight, on the serum lipids levels,
      on psychosocial stress, on high blood pressure and on insulin resistance and
      diabetes mellitus. Physical exercise has also beneficial effects on the balance
      between sympathetic--vagal tone, inducing a vagal predominance, has anti
      atherogenic and anti-ischemic effects, influencing the endothelial function, the
      inflammation (anti-inflammatory effect), both arteriogenesis and angiogenesis and
      thrombosis. Physical training could improve the symptoms of coronary patients by
      preconditioning, which has a protective effect for the myocardium. We may state
      that physical exercise has beneficial effects in cardiovascular patients because
      it increases exercise tolerance with positive consequences on the quality of life
      and professional reintegration, but also because it has positive effects beyond
      this. Thus, physical exercise should be practiced through cardiac rehabilitation
      programs, by all cardiovascular patients.

PMID- 19157268
TI  - Total cardiovascular risk estimation in Romania. Data from the SEPHAR study.
AB  - OBJECTIVE: of this sub-study was to assess the impact of major CV risk factors on
      mortality due to CV diseases among Romanian adult subjects using the SCORE
      System. STUDY DESIGN AND SETTING: In 2005, a survey for CV risk factors (SEPHAR)
      was performed in Romania involving 2017 subjects aged over 18 yrs, a
      representative sample for the Romanian adult population. Romania's area was
      divided into ten regions recommended by The National Commission of Statistics. We
      evaluated the relationship between gender, age, smoking status, systolic blood
      pressure and total cholesterol and cardiovascular risk. Ten year risk of fatal
      cardiovascular disease was estimated according to the SCORE (Systematic COronary
      Risk Evaluation) System. RESULTS: Average total risk in Romanian adult population
      was 3.5%. Male population had a significantly higher risk than females (5.4% vs.
      1.7%, p<0.01). About one fifth of subjects (20.7%) had a high risk > or = 5%.
      Four percent of subjects (all males) had a very high risk > or = 15%. The CV risk
      was relatively homogeneously distributed between Romania's geographic regions.
      The prevalence of hypercholesterolemia as CV risk factor was high (40%), and also
      was the prevalence of high systolic blood pressure (36.6%). The prevalence of
      smoking was similar to other European countries (27%). CONCLUSION: Our study
      showed Romania as a country with a high cardiovascular risk, being also one of
      the regions in Europe with the highest CV risk.

PMID- 19157269
TI  - Lifestyle, cardio-metabolic risk and arterial stiffness.
AB  - HDL-cholesterol plays a key role defining the functional state of the arteries
      and the relation to cardiovascular risk. AIM: To assess the degree of arterial
      stiffness in asymptomatic subjects with and without cardiovascular risk,
      depending on lipidic parameters behavior and on the insulin resistance state.
      METHODS: Arterial stiffness was assessed using the carotid-radial pulse wave
      velocity (PWV-CR) measured with Complior; cardiovascular risk was calculated
      using the SCORE chart; metabolic risk was quantified by assessing fasting lipidic
      (TC, TG, HDL, LDL) and glycemic parameters (HOMA-IR >1 defines the insulin
      resistance state). RESULTS: 58 asymptomatic subjects, 57.62 +/- 14.40 years:
      46.55% with (SCORE > or = 5%) and 53.45% without (SCORE < 5%) cardiovascular
      risk. In subjects with SCORE < 5% and low HDL (< 40 mg/dL), PWV-CR is influenced
      by the TG/HDL ratio (R2=0.27, p=0.04); LDL < 115 mg/dL has a powerful influence
      on PWV-CR (R2=0.58, p=0.02); the association of lipidic alterations is predictive
      for increased PWV-CR (> or = 9.5 m/s) (R2=0.85, p=0.008). In subjects with SCORE
      > or = 5%, protective HDL level (> or = 40 mg/dL) and HOMA-IR > 1, PWV-CR is
      strongly related to the insulin resistance state (R2=0.74, p=0.02), also to the
      association with LDL levels (R2=0.92, p=0.01). CONCLUSIONS: The association
      between low HDL levels and other lipidic alterations in asymptomatic subjects
      with low cardiovascular risk influences the degree of arterial stiffness.
      Increased HDL levels and the presence of insulin resistance syndrome in high risk
      asymptomatic subjects are predictive for arterial stiffness. This prediction is
      amplified by LDL association to the metabolic state of the insulin resistance
      syndrome. It is necessary to establish target levels for HDL and TG in the
      cardiovascular disease prevention guidelines.

PMID- 19157270
TI  - Left atrial surface cut point to detect trapezoidal shape for characterisation of
      atrial anatomical remodeling.
AB  - BACKGROUND: Complete geometrical and shape characterization of left atrium has
      not been performed. Ellipse formula has been proved to underestimate the real LA
      volume. The aim of the study is to analyze the relation between LA area and shape
      in order to predict their value in the assessment of the severity of anatomical
      remodeling. METHODS: 216 consecutive patients (pts) aged 53 +/- 27 years were
      included. The following parameters were assessed: LA dimensions (LAd=M-mode,
      parasternal long axis, LAt and LA1 are the measurements of short- and long-axis
      in apical four chamber view), LA surface in apical four chamber view (LAs). A new
      measurement was introduced, the basal dimension of the LA (LAb) as the maximal
      transverse distance at the base of LA apical four chamber view. LA measurements
      were calculated at end-systole (maximal). Trapezoidal LA shape was defined if
      transverse dimension < basal dimension. RESULTS: LAs ranged 10.5-54.5 cm2.
      Trapezoidal LA was found in 149 pts. ROC curve for prediction trapezoidal LA
      showed a 0.89 area under the curve. The analysis demonstrates a cutoff value of
      22.3 cm2 for LAs to detect trapezoidal shape with a sensitivity of 85% and
      specificity of 82.5%. The simple regression analysis demonstrated a statistically
      significant linear correlation between LAd and LAs (r2=0.63, p<0.0001) but LA1
      was better correlated with LAs (r2=0.7, p<0.0001). Trapezoid LA with
      atrialization of the pulmonary veins and predominant dilatation of bazal atrium
      than annular side may explain underestimation of LA volume using ellipse formula.
      CONCLUSION: LAs is a reliable parameter and may be the best choice to estimate LA
      dilatation; LAs is related to shape remodeling; LA1 is a better parameter than
      LAd for estimating LA dilatation and complete characterization of LA remodeling
      should include shape definition and LAb.

PMID- 19157271
TI  - The impact of the metabolic syndrome on the patients with acute coronary
      syndrome.
AB  - BACKGROUND: The subjects with metabolic syndrome are an increased risk for the
      development of diabetes mellitus and cardiovascular disease as well as an
      increased mortality for cardiovascular disease in all causes. The prevalence of
      the metabolic syndrome after acute coronary syndrome has not been studied yet. We
      aimed to evaluate the prevalence of the metabolic syndrome and to evaluate its
      cardiovascular risk potential using the National Cholesterol Education Program's
      Adult Treatment Panel III (NCEP-ATP III) criteria. METHODS: We performed a cross
      sectional study in 256 patients with acute coronary syndrome. The definition of
      the metabolic syndrome was based on NCEP-ATP III criteria. The cardiovascular
      risk factors that define the metabolic syndrome and their correlation with the
      cardiovascular risk were evaluated by descriptive and interferential statistical
      methods. RESULTS: The prevalence of metabolic syndrome was 47.26%, as assessed by
      criteria of the NCEP-ATP III. The presence of the metabolic syndrome has been
      positively correlated with the cardiovascular risk (OR 1.29; 95% CI, 1.05-1.54,
      p=0.047). The cardiovascular risk has significantly correlated with the
      increasing of the components number that defines the metabolic syndrome. Among
      the components of the metabolic syndrome, HDL-Cholesterol was the most
      significantly correlated with the cardiovascular risk in the patients with acute
      coronary syndrome (OR 3.60; 95% CI 2.14-5.06; p=0.002). CONCLUSION: The
      prevalence of the metabolic syndrome according to the NCEP-ATP III criteria was
      high, and positively correlated with the cardiovascular risk in the patients with
      acute coronary syndrome. The cardiovascular risk rises proportionally with the
      number of metabolic components.

PMID- 19157272
TI  - Cardiac peptides during exercise test in ischemic and non-ischemic heart failure
      patients.
AB  - BACKGROUND: Cardiac peptides are increased at rest in heart failure patients
      representing a useful diagnostic tool for this condition. Recently it has been
      demonstrated that cardiac peptides increase also during myocardial ischemia.
      Cardiac peptides increase during exercise in heart failure patients, but it has
      not been established yet if the increase is the same in ischemic and nonischemic
      patients. METHODS: There were studied 50 heart failure patients, 32 ischemic and
      18 nonischemic, 35 males and 15 females aged 61.8 +/- 11.61 after the relief of
      congestive syndrome, which was submitted to a symptom-limited exercise stress
      test on a cycloergometer. Blood samples were obtained at rest and at a peak
      effort and the plasmatic values of NT-proBNP (NV<250 fmoles/mL) and of NT-proANP
      (NV<1950 fmoles/mL) were determined using the ELISA method. RESULTS: At rest,
      both NT-proBNP and NT-proANP were more increased in nonischemic (1104.33 +/- 730;
      3275.55 +/- 3424) than in ischemic patients (685.68 +/- 452.01, 2265.0 +/-
      2552.32) with significant differences only for NT-proBNP (p=0.016). During
      exercise NT-proBNP increase from 836.40 +/- 596.34 to 1403.92 +/- 2126.21 and NT
      proANP from 2628.80 +/- 2903.41 to 3701.30 +/- 3237.76, the final values being
      again more increased in nonischemic patients (NT-proBNP-2945.44 +/- 3257.89; NT
      proANP-3174 +/- 2905); for NT-proBNP p<0.05. The results suggest that the
      stretching effect during exercise is more increased at the ventricular level in
      comparison with the atrial level (67% increase for NT-proBNP and only 40% for NT
      proANP). Surprisingly, myocardial ischemia does not increase additionally cardiac
      peptides either at rest or during exercise. Our data suggest that the
      intracardiac pressure is more important than ischemia in determining the increase
      of cardiac peptides in heart failure patients because the left ventricular
      ejection fraction was lower in nonischemic patients (40.03 +/- 5.5 vs 38.11 +/-
      4.07). CONCLUSION: Cardiac peptides are increased, both at rest and during
      exercise, in nonischemic heart failure patients in comparison with ischemic ones,
      probably in relationship with the lower left ventricular systolic function.

PMID- 19157273
TI  - Environmental factors and cardiovascular risk in young individuals.
AB  - Normal endothelial function alters physiologically with aging. Intervention of
      environmental factors precipitates and accelerates endothelial dysfunction
      progression, correlated with cardiovascular risk. AIM: To study the impact of
      environmental factors (smoking, nutritional habits, stress, physical activity) on
      the imbalance of the endothelial commuting threshold. METHODS: The questionnaire
      method was applied in order to identify and quantify the presence of
      environmental factors; an anthropometrical physical exam was performed; metabolic
      profile (insulin resistance HOMA-IR, lipid parameters) was assessed. Arterial
      elasticity was assessed with Complior (Artech Medical). RESULTS: The studied lot
      (n=80, 21.16 +/- 2.43 years) comprised young medicine students and showed a high
      incidence of: smoking (31.25%), unhealthy nutritional habits (60%), stress (60%),
      sedentary lifestyle (25%). The odds for endothelial function alteration were
      significant only in subjects who associated stress and smoking (OR=8.18,
      p=0.0006); in the same group, there was noticed the tendency for metabolic
      profile alteration, meaning insulin resistance (OR=1.19, p=ns). The association
      stress-smoking did not significantly influence the unhealthy nutritional habits
      (p=ns, OR=2.39), lipoprotein anomalies (TC > or = 190 mg/dL: p=ns, OR=0.98; LDL >
      or = 130 mg/dL: p=ns, OR=3.53), or the sedentary lifestyle (p=ns, OR=0.80).
      CONCLUSIONS: The main environmental factors which determine endothelial function
      imbalance in young ages are smoking and occupational stress. It is a positive
      stress which does not lead to significant metabolic anomalies or lifestyle
      changes. Though, this kind of stress leads to an unhealthy behavior: smoking. The
      association stress-smoking is essential in endothelial function alteration in
      young subjects. Primary cardiovascular prevention must focus drastically on
      unhealthy behaviors correction to reduce cardiovascular risk in young
      individuals.

PMID- 19157274
TI  - Changes in plasma levels of complement in patients with acute ischemic stroke.
AB  - Inflammatory processes are involved in cerebral ischemia. Patients with ischemic
      stroke may be predisposed to marked activation of the inflammatory system. The
      objective was to analyze the association between the level of complement at
      different stages after stroke and outcome. We collected blood samples from 179
      patients (81 men and 98 women, mean age 73 +/- 5.6 years) within 24 hours after
      ischemic stroke, within 48 to 72 hours and at hospital discharge (16 +/- 7 days)
      as compared to 156 healthy controls, matching ischemic stroke patients with
      regard to sex and age. We measured levels of total hemolytic activity of serum
      complement (EIA method) and of C3, C4 (nephelometric measurements). The data were
      evaluated using chi 2 test. Within 24 hours after ischemic stroke in 38% patients
      mean value of CH50 was 148.4 +/- 57 CH50 U Eq/mL (p<0.05), of C3 was 1.49 +/-
      0.24 mg/L (p<0.05) and of C4 was 0.32 +/- 0.08 mg/L (p<0.05). Within 48-72 hours
      after ischemic stroke in 34% patients mean value of CH50 was 167 +/- 5.9 CH50 U
      Eq/mL (p<0.01), of C3 was 1.58 +/- 0.27 mg/L (p<0.01) and of C4 was 0.38 +/- 0.08
      mg/L (p<0.01). At hospital discharge in 31% patients mean value of CH50 was 192.8
      +/- 64 CH50 U Eq/mL (p<0.001), of C3 was 1.66 +/- 0.28 mg/L (p<0.001) and of C4
      was 0.49 +/- 0.07 mg/L (p<0.001). Patients with ischemic stroke who had elevated
      complement levels (inflammatory marker) at discharge had a worse neurological
      disability; complement might directly contribute to vascular damage.

PMID- 19157275
TI  - Which dose of omega-3 fatty acids must be taken in different cases of
      hypertriglyceridemia?
AB  - Omega-3 fatty acids are very important nutritive agents with a large effect on
      human health. Omega-3 ensures a protective effect on cardiac diseases, arthrosis,
      elasticity of vessels, prolong the bleeding time, improve the theology of the
      blood, protect the endothelium by atherosclerosis, low heart rate and blood
      pressure, reduce the risk for cardiac arrhythmya, etc. It also lowers the
      hypertriglyceridemia. The doses to achieve these effects are still on debate. It
      is very important, at least for the patients with hypertriglyceridemia for which
      omega-3 fatty acids are used constantly, to obtain the maximum of benefits.

PMID- 19157276
TI  - Polycystic hepatic disease.
AB  - Polycystic hepatic disease is a very rare hereditary disease. Most of the
      patients have no symptoms but sometimes they present abdominal discomfort, fever,
      jaundice. Almost half of the patients associate renal cysts. Rarely, the cysts
      may appear in other organs such as the pancreas, the spleen or the lung. We
      present a case of polycystic hepatic disease. In our patient the cysts replace
      almost the entire hepatic structure. However, the hepatic functional tests were
      normal.

PMID- 19157277
TI  - Cryoglobulinemic vasculitis with multiple digital necrosis in viral hepatitis.
AB  - Cryoglobulinemic vasculitis (CV) associated with viral hepatitis C (VHC) is
      halfway between classical autoimmune disease and neoplasia. The extrahepatic
      manifestations of viral hepatitis C are various, their majority being due to
      mixed cryoglobulinemia. Patients diagnosed with viral hepatitis C often have
      mixed serum cryoglobulins, but only 5-10% of them will develop clinically
      manifest cryoglobulinemic vasculitis. CV symptomatology is most frequently
      obvious at skin level. The clinical manifestation characteristic of CV is
      purpura. Digital necrosis as the last stage of trophic disorders associated with
      CV has been rarely described in the literature. All CV types may be complicated
      by renal impairment. A 10-30% proportion of patients with VHC infection will
      develop glomerulonephritis. The treatment of cryobulinemic vasculitis associated
      with viral hepatitis C is focused on the reduction of viral load, the control of
      vasculitis symptoms using corticoids, plasmapheresis, immunosuppressive drugs,
      and the reduction of the amount of cryoglobulins acting on B lymphocytes. We
      present a rare case of cryoglobulinemic vasculitis with multiple digital necrosis
      associated with viral hepatitis C.

PMID- 19157278
TI  - [Swiss intensive medicine: it's time to be active Latins].

PMID- 19157279
TI  - [Intensive care medicine in Switzerland].
AB  - The authors express their views on the past, present and future of intensive care
      medicine in Switzerland. They point some past and present concerns in critical
      care medicine, but they insist on the future needs of this medical specialty: the
      critical patients necessitate, and have the right to obtain, a highly trained and
      specialized personnel, working in strong connection with the whole hospital, in a
      systemic way of treating patients. The authors insist on the very high complexity
      of the ICU-patients treated today.

PMID- 19157280
TI  - [Are hospital network interesting for intensive care medicine?].
AB  - In critical care medicine, collaborative networks are well-developped for
      clinical research. This model is equally interesting for care, education and
      management. For example, in a network, an intensivist can be easily sent to
      another hospital in order to deliver specialized care. In French and Italian part
      of Switzerland, a critical care network was recently founded and it implements
      now several collaborative projects. Networks are very interesting for their
      members because they allows some small ICUs to survive and avoid very expensive
      costs related to restructuration of the larger ones. Thus, this model will
      certainly develop during the next years.

PMID- 19157281
TI  - [Latin program for organ donation: the intensivists are networking].
AB  - The new Swiss federal law on organ and transplantation strengthens the
      responsibilities of the intensive care units. In Italian and French speaking
      parts of Switzerland, the Programme Latin pour le Don d'Organe (PLDO) has been
      launched to foster a wider collaboration between intensivists and donation
      coordinators. The PLDO aims at optimising knowledge and expertise in organ
      donation through improvements in identification, notification and management of
      organ donors and their next of kin. The PLDO dispenses education to all
      professionals involved. Such organisation should allow increasing the number of
      organs available, while improving healthcare professionals experience and next of
      kin emotion throughout the donation process.

PMID- 19157282
TI  - [Lausanne Cohort of septic patients as an opportunity to develop
      multidisciplinary research within the Swiss Latin Network of Intensive Care
      Medicine].
AB  - Despite recent medical progresses in patient support, the mortality of sepsis
      remains high. Recently, new supporting strategies were proposed to improve
      outcome. Whereas such strategies are currently considered as standard of care,
      their real impact on mortality, morbidity, length of stay, and hence, health care
      resources utilization has been only weakly evaluated so far. Obviously, there is
      a critical need for epidemiologic surveys of sepsis to better address these major
      issues. The Lausanne Cohort of septic patients aims at building a large clinical,
      biological and microbiological database that will be used as a multidisciplinary
      research platform to study the various pathogenic mechanisms of sepsis in
      collaboration with the various specialists. This could be an opportunity to
      strengthen the collaboration within the Swiss Latin network of Intensive Care
      Medicine.

PMID- 19157283
TI  - [Informed consent for intensive care research in Switzerland: any solution?].
AB  - In this article, we describe several aspects of the problems linked with the
      informed consent for medical research in the particular environment of intensive
      care. The specific elements of this singular context are analysed in taking
      account the present laws in Europe as well as in Switzerland, including the
      future project of law under current discussion.

PMID- 19157284
TI  - [Physiopathologic aspects of microcirculation in intensive care].
AB  - In critical care patients, microvascular alterations and perfusion heterogeneity
      play an important role in the persistence of cellular hypoxia despite a
      satisfactory functioning of the macrocirculation. Advance in the knowledge of
      microcirculatory pathophysiology, and its relation with the macrocirculation
      could be in the future a way to improve the outcome of critically ill patients.
      Moreover, the evolution of clinical practice towards microcirculation monitoring
      as a standard of care, with new therapeutic targets aimed to increase tissue
      perfusion, could be a revolution in critical care practice.

PMID- 19157285
TI  - [Up-to-date resumes of the systematic evaluation of efficacy of medical
      interventions ].

PMID- 19157287
TI  - [The art of giving thanks].

PMID- 19157286
TI  - [Osteoporotic fracture in menopausal women: alendronate reduces the risk].

PMID- 19157288
TI  - [To finish theoretically with AIDS].

PMID- 19157289
TI  - [A very sad post card from Zimbabwe].

PMID- 19157290
TI  - [End of life: affirmation a French position].

PMID- 19157292
TI  - [DRG: a revolution on the wrong side].

PMID- 19157291
TI  - [Europe does not want to eat cloned food].

PMID- 19157293
TI  - [Construction and expression of Plasmodium berghei chimeric protein in Pichia
      pastoris and its immunogenicity in mice].
AB  - OBJECTIVE: To produce an erythrocytic stage chimeric protein of Plasmodium
      berghei in Pichia pastoris and evaluate its immunogenicity. METHODS: The DNA
      sequences of AMA1 (III) and MSP1-19 from P. berghei homologous to the
      corresponding sequences of P. falciparum chimeric antigen 2.9 (PfCP-2.9) were
      fused to generate a chimeric gene, designated as PbCP-2.9. The resulting gene was
      redesigned using Pichia preferential coden usage and expressed in P. pastoris in
      the secreted form. The recombinant protein was purified by Ni-NTA affinity
      chromatography. Three groups each with 10 BALB/c mice were immunized
      subcutaneously with 20 microg of purified PbCP-2.9 antigen formulated in Freund's
      adjuvant, Montanide ISA720 and Montanide IMS 1312, respectively. Three control
      groups each with 10 mice received only adjuvants emulsified with PBS. All the
      mice received three immunizations at 2-week intervals with the same dose of
      antigen. Serum samples were collected at pre-immunization and one week after each
      immunization, and were analyzed for specific antibodies by ELISA and reaction
      with natural P. berghei proteins by IFAT. RESULTS: The PbCP-2.9 antigen with Mr
      26400 was successfully expressed in P. pastoris in secreted form. The recombinant
      protein can be recognized by the serum against blood stage parasites of P.
      berghei. High antibody responses were detected in all three PbCP-2.9-immune
      groups of mice by ELISA. However, mice immunized with PbCP-2.9 antigen in
      Freund's adjuvant produced higher antibody titers than those with PbCP-2.9
      antigen in Montanide ISA 206 and Montanide IMS 1312 adjuvants. The mean antibody
      titer in Freund's adjuvant was 6.9-fold higher than in Montanide ISA 206 adjuvant
      and 5.6-fold higher than in Montanide IMS 1312 adjuvant after the second
      immunization (F=81.06, P< 0.01). In addition, after the third immunization the
      mean antibody titer in Freund's adjuvant was 3.7-fold higher than in Montanide
      ISA 206 adjuvant and 3.3-fold higher than in Montanide IMS 1312 adjuvant
      (F=13.29, P< 0.01). The results from IFAT assay demonstrated that the immune sera
      recognized the surface proteins of P. berghei parasites. CONCLUSION: The coden
      optimized PbCP-2.9 gene has been constructed and expressed in P. pastoris. The
      chimeric antigen is highly immunogenic in mice and the immune sera can interact
      with natural proteins of P. berghei parasite.

PMID- 19157295
TI  - [In vitro potentiation of chloroquine activity in Plasmodium falciparum by
      ketotifen and cyproheptadine].
AB  - OBJECTIVE: To study the potentiation of chloroquine activity and mechanism by
      ketotifen and cyproheptadine in in vitro cultured Plasmodium falciparum Fcc
      SM1/yN strain. METHODS: In vitro cultured Fcc SM1/yN strain was added to pre
      prepared drug plates at 50 microl/well after synchronization to make final
      concentration of 0.3125-2560 nmol/L for chloroquine and of 9.80-5000 nmol/L for
      ketotifen or cyproheptadine. After 34 hours' culture in 37 degrees C, the number
      of schizonts with 3 or more nuclei was calculated among 200 parasites under
      microscope. Calculated half inhibitive concentration (IC50) of chloroquine and
      every drug combination to parasite as well as chloroquine activity enhancement
      index (AEI) of ketotifen (or cyproheptadine). Time dependency of potentiation was
      studied. All data were analyzed statistically with SPSS 13.0. After 20 hours'
      action of one optimal combination dose of chloroquine/ketotifen or
      chloroquine/cyproheptadine, RNA of the Fcc SM1/yN strain was extracted and real
      time PCR was used to determine the expression level of pfcrt and pfmdr1 genes.
      RESULTS: The best potentiation effect was observed with ketotifen or
      cyproheptadine of 625 nmol/L, with IC50 of 74.53 nmol/L for chloroquine/ketotifen
      and 89.7 nmol/L for chloroquine/cyproheptadine respectively, and activity
      enhancement index (AEI) of 0.42 for chloroquine/ketotifen and 0.30 for
      chloroquine/cyproheptadine respectively. Combination of 625 nmol/L ketotifen or
      cyproheptadine with 5 nmol/L chloroquine showed the highest potentiation potency.
      6-7 hours during which ketotifen or cyproheptadine was added after chloroquine
      showed the highest effect, with IC50 of 67.70 nmol/L for chloroquine/ketotifen
      and 81.53 nmol/L for chloroquine/cyproheptadine respectively, and the AEI was
      0.47 for chloroquine/ketotifen and 0.37 for chloroquine/cyproheptadine
      respectively. After action of chloroquine/ketotifen or chloroquine/cyproheptadine
      at one optimal combination dose, expression level of pfcrt gene increased by 91%
      and that of pfmdr1 gene decreased by 14% respectively. CONCLUSION: Appropriate
      combination of chloroquine/ketotiphen or chloroquine/cyproheptadine potentiates
      chloroquine against in vitro cultured P. falciparum. 6-7 hour period is an
      optimal time when ketotifen or cyproheptadine was added after chloroquine.
      Potentiating activity of ketotifen and cyproheptadine may be related to the
      expression level of pfcr t and pfmdr1 genes.

PMID- 19157294
TI  - [In vitro observation on the apoptosis induced by H2O2 in protoscolex of
      Echinococcus granulosus].
AB  - OBJECTIVE: To explore the apoptosis induced by hydrogen peroxide (H2O2) in
      protoscolex of Echinococcus granulosus. METHODS: Protoscoleces were cultured in
      vitro, and used for the experiment in 2 groups: RPMI 1640 medium and RPMI 1640
      medium added with glutamine. They were then treated with different concentrations
      of H2O2 to induce apoptosis. Terminal deoxynucleotidyl transferase-mediated dUTP
      nick end labeling assay (TUNEL) was employed to observe the apoptosis. Protein
      expression of caspase-1, caspase-3 and Fas was detected by SP immunohistochemical
      technique, stained with DAB restained with hematoxylin. A yellow or brown color
      nucleus revealed positive apoptosis cells in protoscolex, a brown reaction
      product in cytoplasm showed positive cells of caspase-1 and caspase-3, and brown
      cell membrane and cytoplasm revealed Fas product; otherwise it was judged as
      negative. According to the percentage of positive cells in a protoscolex, the
      expression level was divided as 4 grades. The percentage of less than 5% was
      regarded as "-", 5%-25% as "+", 26%-50% as "++", more than 50% as "+++". The
      experiments were repeated 2 times with controls. RESULTS: In RPMI 1640 group,
      positive TUNEL was found in the protoscolex induced by 1 mmol/L H2O2 inducing for
      12 hours. Induced by 1 mmol/L H2O2 for 4 h, the "+-++" expression rate of caspase
      1 and caspase-3 in the protoscoleces was 86.6% and 77.8%, and for 8 h, 86.6% and
      80.0% respectively, a significant increase in comparison to the control (P<0.05).
      Induced by 5 mmol/L H2O2 for 4 hours, the "++-+++" expression rate of caspase-1
      was 93.0%, and the "+-++" expression rate of caspase-3 was 89.5%; induced for 8
      h, the "++-+++" expression rate of caspase-1 decreased to 53.2%, and the "+-++"
      expression rate of caspase-3 decreased to 48.4% and "-" expression rate increased
      to 46.8%. Under 5 mmol/L H2O2 for 4 h the expression rate of caspase-3
      significantly decreased at 8 h (P<0.01). In the group of RPMI 1640 plus
      glutamine, induced by 5 mmol/L H2O2 for 8 h, the "++ -+++" expression rate of
      caspase-3 in protoscolex was 100% (P<0.01). However, in RPMI 1640 group, induced
      by 5 mmol/L H2O2 for 8 h, the "++-+++" expression rate of caspase-3 in
      protoscolex was 32.2% and 46.8% were negative. The Fas product with positive
      reaction in protoscolex was found in both control and induced groups: in RPMI
      1640 group, under 5 mmol/L H2O2 induced for 4 h, "+-++" expression rate was 53.0%
      and control was 20.0%; and in the group of RPMI 1640 plus glutamine, under 5
      mmol/L H2O2 induced for 8 h, "+-++" expression rate was 88.7% and control was
      71.4%, increased in both groups after induction (P <0.05). CONCLUSION: Apoptosis
      in the protoscolex of E. granulosus may be induced by H2O2.

PMID- 19157296
TI  - [Epidemiological survey on malaria situation in Motuo County of Tibet, China].
AB  - OBJECTIVE: To make an epidemiological investigation on malaria in Motuo County,
      Linzhi Prefecture of Tibet. METHODS: In July of the year 2006, the following
      activities were conducted in 2 selected villages from each of the three
      townships, i.e., Motuo, Dexing and Beibeng: malaria history survey among
      inhabitants in recent 2 years; collection of blood samples of inhabitants for
      examining malaria parasites, IFAT and detecting G6PD, respectively; mosquito
      collection in human dwellings and cattle shelters at night and various resting
      sites at day-time; mosquito collection by outdoor human baiting capture;
      classification and composition calculation of mosquito species and man biting
      rates; ELISA for detecting sporozoite infection of Anopheles. RESULTS: The mean
      rate of two-year malaria history was 8.98% (118/1314) and the parasite rate was
      3.13% (38/1216, all P. vivax) in the inhabitants. The parasite positive rate
      among the feverish patients was 7.14% (3/42). IFAT revealed a malaria antibody
      rate of 40.24% (472/1173). The G6PD deficiency rate was 1.74% (21/1208). Five
      hundred and thirteen anopheline mosquitoes were caught. They were An. maculatus
      (474) which occupied 92.4% (474/513), An. peditaeniatus (35), An. kochi (3) and
      An. sinensis (1). The mean indoor density of An. maculatus was 4.75/night in
      human houses, and 69.5/night in cattle shelters. The outdoor human biting rate
      was 22.75/half-night/person, and the sporozoite rate of An. maculatus in
      anopheline saliva glands was 0 by ELISA. CONCLUSION: Motuo County is an endemic
      area of vivax malaria with An. maculatus as the potential vector.

PMID- 19157297
TI  - [Artesunate in interrupting the transmission of Plasmodium falciparum].
AB  - OBJECTIVE: To observe the effect of artesunate (ATS) on the infectivity of
      Plasmodium falciparum gametocytes (PFG). METHODS: 31 volunteers with falciparum
      malaria and gametocytaemia were randomly divided into 3 groups: artesunate (ATS)
      group (15 cases), quinine (QN) group (10 cases) and placebo group (6 cases). Each
      case in ATS group received 6-day course of oral artesunate (200 mg at 0, 6 and 24
      hours then 100 mg daily for 4 days). Cases in QN group each received 21-dose
      course of quinine sulfate (500 mg/time) over seven days. Cases in placebo group
      took 2 tablets of vitamin B composites, three times per day for seven days.
      Peripheral PFG were counted daily in all cases until the clearance of PFG.
      Mosquitoes (Anopheles dirus) were fed with venous blood of patients on the 1st,
      7th, 14th, 21st and 28th day, respectively. RESULTS: All cases in placebo group
      were PFG positive at the whole course by blood smear examinations. The PFG
      relative density in ATS group were (12.5+/-3.3)%, (1.2+/-0.4)%, (0.3+/-0.1)% on
      7th, 14th, 21st day respectively, and the mean PFG clearance time was (22.0+/
      1.4) d. The PFG relative density in QN group were (173.9+/-47.0)%, (112.5+/
      45.4)%, (32.5+/-17.8)% at 7th, 14th, 21st day respectively, and the mean
      clearance time of PFG was (32.5+/-2.1) d (t=4.731, P<0.01). PFG remained positive
      on the 28th day in placebo group. The infectivity test to mosquitoes showed on
      14th day the positive rate in ATS group, QN group and placebo group were 0, 35.0%
      and 48.7% respectively. In ATS group, the sporozoite rate of anopheline
      mosquitoes were 14.8% and 0 at 7th, 14th day, while in QN group, 142.0%, 98.6%
      and 20.3% at 7th, 14th, 21st day respectively. In placebo group, the infection
      rate of sporozoites remained stable. CONCLUSION: Oral administration of
      artesunate with a total dosage of 1000 mg in 6 days inhibits the infectivity of
      PFG.

PMID- 19157298
TI  - [Pathological change in the brain of mice infected with Angiostrongylus
      cantonensis].
AB  - OBJECTIVE: To observe the pathological change in the brain of Angiostrongylus
      cantonensis-infected mouse. METHODS: Forty-eight mice were orally infected each
      with 40 third stage larvae of A. cantonensis, 3 mice were sacrificed at 7, 10,
      13, 16, 19, 22, 25, 28 days postinfection respectively for worm recovery, and
      another 3 mice were for observing the histopathological change in tissue sections
      of the brain. RESULTS: Ten days postinfection, worms were found in the brain of
      the infected mice with a mean worm number of (7.0+/-1.7) per mouse. The highest
      number of worms was found at 16 days postinfection, with a mean of (23.7+/-4.9)
      per mouse. Notable symptoms of nervous system were seen on 15 days postinfection.
      Most mice died around 22 days postinfection. Histological examination revealed
      mechanical damages. Cavities and inflammation were observed in the brain
      parenchyma. Worms were seen in the subarachnoid space. Meningitis-like signs
      started at 13 days and aggravated then. CONCLUSIONS: Infection of A. cantonensis
      causes pathological change in mouse brain and the process is aggravating with
      postinfection time.

PMID- 19157299
TI  - [Cloning, expression and purification of allergen arginine kinase from
      Periplaneta americana and its allergic activity].
AB  - OBJECTIVE: To clone the gene of arginine kinase (AK) from Periplaneta americana,
      produce its recombinant protein and investigate its allergenicity. METHOD: The
      cDNA of AK was cloned using specific primers from the total RNA of P. americana.
      The cloned gene was inserted into pMD18-T vector and digested by BamHI and
      HindIII. The cDNA was sequenced and subcloned into pET-28a expression vector. The
      cloned AK cDNA gene was expressed in Escherichia coli BL21 (DE3) by IPTG
      induction. The recombinant AK (rAK) was purified by metal (Ni2+) chelating
      affinity chromatography. Its allergenicity was examined by both Western blotting
      and enzyme-linked immunosorbent assay (ELISA). RESULT: The cloned cDNA ORF
      sequence (Accession no. EU429466) contained 1068 bp and encoded 365 amino acids.
      Its sequence homology with the published one (Accession no. AY563004) was 99.9%
      at nucleotide level. The allergen rAK was highly expressed in E. coli BL21 (DE3)
      as a soluble protein mainly with the molecular weight of about Mr 45000 under
      induction of IPTG and purified by 6-His-tag purification system. Both in the non
      denaturalization and denaturalization conditions, the recombinant allergen was
      identified as its affinity to IgE antibodies from the cockroach-allergic patient
      sera by Western blotting and ELISA. CONCLUSION: The recombinant cockroach
      arginine kinase has been obtained with proper allergenicity.

PMID- 19157300
TI  - [Effect of the liposome albendazole and Huai-Er fungus extract on hepatic
      infection of Echinococcus granulosus in mice].
AB  - OBJECTIVE: To explore the effect of Huai-Er fungus extract (HEF) and liposome
      albendazole (L-ABZ) on the hepatic infection of Echinococcus granulosus (Eg) in
      mice, and understand the influence of improved host immunity on postoperative
      recurrence. METHODS: Female Kunming mice were immune by intraperitoneal injection
      Eg cyst fluid from sheep, IgG positive mice were divided into drug treatment
      groups (A, B and C) and control group (D). Mice in group A were administered by
      gavage with single L-ABZ (75 mg/kg), group B with single HEF (15,000 mg/kg), and
      group C with combination therapy (L-ABZ 75 mg/kg plus HEF 15,000 mg/kg), once
      every two days for one week. The protoscoleces were treated with balanced
      solution for 20 minute and inoculated in the liver by open abdomen of the
      anesthetized mice. Imitating to an "open sub-adventitial total exocystectomy",
      protoscoleces outside the cyst led to a reinfection. 72 hours later, groups A, B
      and C were re-treated for a month. Mice in group D were given with distilled
      water (0.3 ml per mouse). Group E was set as blank control (n=8). Another 120 IgG
      positive mice were divided as groups F, G, H and I, and treated in parallel with
      the groups A, B, C and D respectively; these mice were inoculated with
      protoscoleces which were treated in advance with 75% alcohol, 20% hypertonic
      saline, L-ABZ and PBS for 20 min respectively. In 3 months after infection, all
      the mice were sacrificed to evaluate the efficacy, which covered infection rate,
      pathological change, spleen index, level of IgG and IgE, CD4+ and CD8+ cells.
      RESULTS: The recurrence rate in group C (5.7%) was lower than that of groups A
      (17.1%) and B (24.2%), with hydatid cysts in white colour and nodular, showing
      degeneration of the germinal and laminated layers. Groups A, B and C showed lower
      spleen index (A: 3.84+/-0.86, B: 3.95+/-1.01, and C: 3.27+/-0.52), and lower IgE
      level (A: 0.06+/-0.08, B: 0.07+/-0.08 and C: 0.03+/-0.03) than group D (5.46+/
      0.52 and 0.20+/-0.02, respectively) (P<0.05), especially in group C; and also
      lowerCD8+ in groups A (16.61+/-3.89), B (18.18+/-3.90) and C (15.38+/-2.63) than
      group D (32.90+/-4.71) (P<0.05), but higher CD4+/CD8+ in groups A (3.21+/-0.70),
      B (3.05+/-0.66) and C (3.53+/-0.57) than group D (1.57+/-0.26) (P<0.05),
      especially in group C. The infection rate of mice in group F, Gand H was 0, 0 and
      23.1% respectively, and that of group I, 31.2% (P<0.01). CONCLUSION: The
      combination of HEF and L-ABZ considerably improves the immunity of the hosts and
      HEF may have a synergetic action to L-ABZ in reducing the recurrence of "sub
      adventitial total exocystectomy". 75% alcohol and 20% hypertonic saline show
      better effect of inactivating protoscoleces than L-ABZ in surgical operation.

PMID- 19157301
TI  - [Killing effect of polymorphonuclear neutrophils on Trichomonas vaginalis].
AB  - OBJECTIVE: To study the killing effect of polymorphonuclear neutrophils (PMNs) on
      Trichomonas vaginalis. METHODS: The vaginal secretion from a patient with
      vaginitis was incubated in the liver infusion liquid medium to get T. vaginalis.
      One ml serum was collected from the patient and heated for 30 min at 56 degrees C
      to inactivate complement in serum, and was absorbed three times with the
      parasites at 0 degree C to make the serum free of antibodies. PMNs were separated
      from the patient's blood and purified with density gradient centrifugation and
      polymer accelerating sedimentation. NBT and safranin O were used to stain the
      sample. The interaction between PMNs and the parasites was observed under
      microscope. 300 trichomonads and 3x10(4) PMNs were incubated for 10, 20, 30, 40,
      50, 60 minutes under the conditions of aerobic or anaerobic, with superoxide
      dismutase (SOD) and catalase (CAT) or without SOD and CAT, and with complement or
      without complement. They were then inoculated in solid medium for another five
      days under the anaerobic condition, and surviving organisms were enumerated.
      RESULTS: PMNs were observed to surround and kill a single trichomonad. In the
      petri-dish containing PMNs, the surviving rate of the parasites in anaerobic
      condition was 85%, only 3% in aerobic condition (P<0.01). SOD and CAT reduced the
      killing effect of PMNs, with a surviving rate of 98% and 94% respectively after
      60 min incubation. Without SOD and CAT, the surviving rate is only 2% (P<0.05).
      PMNs in the serum without antibodies killed all the parasites, while the
      complement-inactivated serum fail to kill them. CONCLUSION: The trichomonacidal
      activity of PMNs relies on the presence of oxygen and complement in the serum of
      patient.

PMID- 19157302
TI  - [Epidemiological investigation of Angiostrongylus cantonensis in Jiangmen of
      Guangdong Province].
AB  - OBJECTIVE: To make an epidemiological survey on Angiostrongylus cantonensis in
      Jiangmen City of Guangdong Province. METHODS: From October 2006 to November 2007,
      the characteristics of A. cantonensis infection were investigated in Jiangmen
      district in various hosts, including the third stage larva infection in the
      snails Achatina fulica and Pomacea canaliculata by digestion method, and the
      adult A. cantonensis in rats by the dissection of heart and lungs. Relevant
      symptoms and dietary habits in Jiangmen residents who were randomly recruited
      were also investigated by questionnaire, and the specific IgG and IgM antibodies
      against A. cantonensis in their sera were detected by ELISA. RESULTS: 695 A.
      fulica and 720 P. canaliculata were examined. The infection rate of third stage
      larva of A. cantonensis were 45.0% and 1.8% respectively, with an infectivity of
      53.74+/-147.30 and 5.23+/-8.51 respectively. Natural infection rate of A.
      cantonensis in all 229 rats was 4.4%. Among the 300 people surveyed, 11.3% had a
      history of eating raw or undercooked fish and shrimp, 5.3% directly or indirectly
      exposed to A. fulica or P. canaliculata. The positive rate of specific IgG
      antibody against A. cantonensis for serum samples among residents was 14.0%
      (42/300), and 5 serum samples in the 42 positive samples showed specific IgM
      antibody, with a positive rate of 1.7%. CONCLUSION: Jiangmen district is an
      endemic area of A. cantonensis, and the local residents are under the risk of
      infection.

PMID- 19157303
TI  - [Two imported cases of vivax malaria].

PMID- 19157304
TI  - [Analysis on 2175 admitted cases of clonorchiasis sinensis in Guigang City].
AB  - OBJECTIVE: To understand the epidemiological features of the hospitalized cases
      with Clonorchis sinensis infection in Guigang City of Guangxi Region. METHODS:
      Fecal samples were collected from patients each with 30-50 g and examined by
      sedimentation technique. Number of eggs was counted in randomly selected cases by
      Stoll's method. With the number of eggs per gram (EPG) feces, light, medium and
      heavy intensity of infection were identified as EPG< or =500, 501-5,000 and
      >5,000 respectively. RESULTS: Among 2,175 cases with clonorchis eggs, 1,244 cases
      showed clinical complications (57.2%). The average EPG in 61 cases counted was
      3055, 34 (55.7%) showed medium or heavy intensity of infection. The cases
      distributed in 80% of the townships, more concentrated in 2 towns and 1 farm. The
      patients aged between 3 to 76 years old with a ratio of male to female 3.6:1.
      45.5% of the cases were farmers. 1,308 cases (60.1%) were Zhuang Minority. The
      number of cases seeking medical treatment increases year by year since mid-1980s.
      66.0% of the cases had a habit of raw fish-eating. CONCLUSION: Clonorchiasis
      sinensis widely distributes in Guigang City, number of cases admitted in
      hospitals increases yearly.

PMID- 19157305
TI  - [The neglected intestinal parasite co-infection with AIDS].
AB  - In order to increase the recognition of intestinal parasitic infections in AIDS,
      this article reviews the common intestinal parasites co-infected in HIV carriers
      and AIDS patients, namely, Cryptosporidium spp., microsporidia, Giardia lamblia,
      and Strongyloides stercoralis, referring to aetiology, epidemiology, clinical
      features, diagnosis and prevention.

PMID- 19157306
TI  - [Th17 in the immunity against parasitic infection].
AB  - Th17 lymphocytes have been recently identified as a novel subset of CD4+ cells.
      It has been defined that IL-17, the main product of Th17, plays an important role
      in immunity against parasitic infection. There is a two-way influence between
      Th17 and cytokine network: on one hand Th17 consummate cytokine network, on the
      other hand many cytokines regulate Th17's activity in parasitic infection. In the
      anti-parasitic infection process, Th17 cells protect host or promote
      inflammation, even cause immune pathogenesis in different cases, which comprise
      host's immune state, the burden of parasitic infection, as well as the treatment.

PMID- 19157307
TI  - [In vitro effect of medicinal scorpion on the larvae of Ancylostoma caninum].
AB  - Five gram stool sample from dog infected with Ancylostoma caninum was smeared on
      filter paper for routine cultivation under 35 degrees C with moist condition for
      24 hours. Hookworm larvae were separated and divided into 3 bottles through
      precipitation-washing method. Traditional Chinese medicine scorpion (2 ml),
      albendazole (10 mg) and normal saline (2 ml) (control) were added respectively
      into the 3 bottles, which were cultured for another 24 hours. The growth and
      development of the larvae were observed under microscope. In scorpion group, the
      larva body shrank, development stopped, and with an unclear internal structure.
      Treated with albendazole, the larvae became rigid and shriveled with rough body
      surface and vague internal structure. The results indicate that both medicinal
      scorpion and albendazole have considerable effect in inhibiting the development
      of hookworm larvae and the effect of albendazole is stronger.

PMID- 19157308
TI  - [Construction of cDNA expression library of salivary gland from Boophilus
      microplus].
AB  - Total RNA were isolated from salivary gland dissected from partially engorged
      Boophilus microplus. The mRNA was purified. A library of oligo (dT)-primed cDNA
      with added directional EcoR I/Hind III linkers was constructed from the purified
      mRNA. The constructed cDNA was ligated to the EcoR I/Hind III arms of the lambda
      SCREEN vector. The recombinant phage DNA was packaged by phage-marker packaging
      extracts, resulting in a primary cDNA library with a size of 1.38x10(6) PFU. Data
      showed 100% of the library were recombinant and the titer of the amplified
      library was 2x10(9) PFU/ml. A partial cDNA encoding cytochrome oxidase C subunit
      II of B. microplus was screened from the expression library with rabbit serum
      against B. microplus salivary gland proteins. The results is suggested that the
      cDNA expression library has been constructed.

PMID- 19157309
TI  - [Morphological observation on the reproductive system of adult Schistosoma
      japonicum under confocal laser scanning microscopy].
AB  - BALB/c mice were infected with Schistosoma japonicum cercariae (40+/-2 per mouse)
      through abdominal skin. Mice were sacrificed after 35 days to acquire the adult
      worms which were then fixed, stained, clarified, dehydrated and mounted. The
      specimens were observed under the confocal laser scanning microscope. The overall
      morphology of the adult worms was displayed distinctly, especially the testicular
      lobes, seminal vesicle and genital pore of the male, reproductive system, and the
      ovary, vitelline glands, oviduct, vitelline duct, seminal receptacle, ootype,
      mehlis gland, uterus, genital pore and eggs of female reproductive system. The
      confocal laser scanning microscopy is an alternative method to research organs,
      tissues and cell structure of schistosome worm.

PMID- 19157310
TI  - [Preliminary investigation on phylogenetic relationship among three common
      species of house dust mites].
AB  - Dermatophagoides farinae, D. pteronyssinus and Euroglyphus maynei were used for
      the investigation. The cDNA fragment coding for Der f1 and Der f2 were amplified
      by PCR, cloned and sequenced. By bioinformatics softwares, the amino acid
      sequences for Der f1 and Der f2 were deduced and compared with those for the
      groups 1 and 2 allergens of D. pteronyssinus and E. maynei available in GenBank.
      Amino acid sequence similarity analysis showed that Der p1 shared 84% identical
      residues with Eur m1 and 83% with Der f1. Similarly, Der p2 shared 87% identical
      residues with Eur m2 and 68% with Der f2. In the two phylogenetic trees
      constructed with group 1 and 2 allergens, D. pteronyssinus was clustered with E.
      maynei but not with D. farinae, although D. pteronyssinus and D. farinae belong
      to the same genus. D. pteronyssinus should be more similar to E. maynei than to
      D. farinae at evolutional level, which was not consistent with the conventional
      taxonomical relationship based on their morphological characteristics.

PMID- 19157311
TI  - [Observation on mitosis of Trichomonas vaginalis cultivated in vitro using
      modified Giemsa staining].
AB  - The observation showed that the percentage of Trichomonas vaginalis trophozoites
      at the stages of interphase, binary fission and multiple fission was 66.5%, 24.1%
      and 9.4% respectively. Cells in binary fission could be classified as premitotic
      phase, prophase, metaphase, anaphase and telophase. 3 to 8 microcosms were seen
      in one trophozoite under multiple fission and the percentage of trophozoites with
      3 and 4 microcosms occupied 69% and 24.5% respectively. Cells with abnormal
      morphs were also observed.

PMID- 19157312
TI  - [A case of encephalic paragonimiasis].

PMID- 19157313
TI  - [Case treatment of hydatid disease in pelvic cavity complicated with urethral
      fistula].

PMID- 19157314
TI  - [Two cases infected by Psychoda larvae in Yunnan Province].

PMID- 19157315
TI  - Unsafe abortion: global picture and situation in Pakistan.

PMID- 19157316
TI  - Achalasia in a gastroenterology unit of Karachi.
AB  - OBJECTIVE: To study the presentation of Achalasia and compare the response of
      pneumatic dilatation with surgery. METHODS: Retrospective analysis of patient's
      records (January 2000-December 2005) from outpatients department of Pakistan
      Medical Research Council), Jinnah Postgraduate Medical Centre, Karachi was done.
      All patients with Achalasia were analyzed. As a protocol endoscopy, esophageal
      manometry, esophageal transit time and barium swallow was done to establish the
      diagnosis. Surgery and endoscopic guided pneumatic dilatation were offered to
      these patients as treatment options. Patients undergoing surgery or pneumatic
      dilatation were later followed to assess the efficacy and those not responding to
      second dilatation were also operated and follow up of all these cases were noted.
      RESULTS: Forty-six patients (24 males, 22 females) with a mean age of 39.8 +/-
      15.9 years were analyzed. Dysphagia was the primary symptom in thirty eight
      patients (83%) followed by vomiting and epigastric pain. Pneumatic dilatation was
      performed in 32 out of forty-six patients. Out of these cases 22 (69%) had
      single, and 10 (31%) had two dilatations. Two patients (6%) had perforation, one
      required emergency surgery, another patient was managed conservatively and
      recovery was unremarkable. Six patients (19%) later required surgery. Fourteen
      cases opted for surgery as a primary treatment. Out of 20 patients operated, four
      (20%) required post operative dilatation and one (5%) developed gastro-esophageal
      reflux. CONCLUSIONS: Achalasia is prevalent in young age, in both sexes almost
      equally. Pneumatic dilatation is safe and effective, as it can be managed on
      outpatient basis with little morbidity and 81% success rate. Surgery is still an
      effective procedure with comparable 80% success rate.

PMID- 19157317
TI  - Knowledge and practices regarding cigarette smoking among adult women in a rural
      district of Sindh, Pakistan.
AB  - OBJECTIVE: To determine the prevalence of cigarette smoking and to obtain
      information on socio-demographic factors and attitude regarding cigarette smoking
      among adult women in a rural district of Sindh Province, Pakistan. METHODS: A
      cross sectional community based survey was done in a rural district of Sindh
      province of Pakistan using a two stage cluster sampling design. A pre tested
      questionnaire was used to interview 502 adult women (aged 18- 60 years) from the
      study site. The study was approved by the ethical research committee and informed
      consent was taken from participants. RESULTS: A total of 502 women were
      interviewed for this study. Approximately 71% of women were illiterate and 44% of
      women were in the age group of 18-24 years. A high number (10%) of adult women
      were smokers. Age at initiation among women (18-24 years) was 42%. A significant
      difference for questions regarding smoking effects on health (p = 0.02) and
      knowledge regarding smoking causes respiratory disease (p = 0.02) was observed in
      this survey. CONCLUSION: It was concluded that the prevalence of smoking among
      women is on the rise in this rural district of Pakistan. Young age at initiation
      is an important finding that needs to be addressed.

PMID- 19157319
TI  - Knowledge, attitude and behaviour of mothers on neonatal jaundice.
AB  - OBJECTIVE: To determine knowledge, attitude, and behaviour of mothers about
      neonatal jaundice. METHODS: In this cross-sectional study, 400 cases who
      delivered at Ali-Ebne Abitaleb Hospital in Zahedan-Iran during April and May 2006
      were interviewed to complete 21-point questionnaires. The first data was analyzed
      descriptively then analytically by chi2, Pearson correlation, and independent t
      test using SPSS 11 software. RESULTS: The mean age of mothers was 26.8+/-6.5
      years. The mean of knowledge score was 7.25+/-2.1 out of 13.5. Although knowledge
      of mothers about diagnostic methods was acceptable, it was not sufficient about
      causes, complications, harmful symptoms and prevention of the disease. The mean
      of attitude score was 18.5+/-3.7 out of 25. The mean of behaviour score was 6.8+/
      2.3 out of 10.5. Knowledge had a significant association with history of neonatal
      jaundice (P=0.033), mother's age (P<0.001), and child's birth rank (P=0.001).
      There was also a significant association between mother's attitude and their
      educational level (P<0.001). Results showed a direct correlation between
      knowledge, attitude and behaviour (P<0.001). CONCLUSION: Increasing mothers'
      knowledge about jaundice of neonates can be the first step to enhance healthy
      behaviours; through education programmes during pregnancy.

PMID- 19157318
TI  - A randomized effectiveness trial of methadone, TENS and methadone plus TENS in
      management of opiate withdrawal symptoms.
AB  - OBJECTIVE: To compare effectiveness of methadone, TENS (Transcutaneous Electrical
      Nerve Stimulation) and methadone+ TENS in management of opiate withdrawal
      symptoms. METHODS: The study was conducted in Zahedan Psychiatric center in 2005.
      Forty five opiate addicted men meeting DSM-IV criteria for substance dependency
      disorder participated in the study after informed consent. The subjects were
      randomly assigned to 3 treatment groups. Patients of first group were given 20-60
      mg methadone daily, tapered over a period of 2 weeks. Patients of second group
      received daily 10-30 mg methadone, tapered similar to first group in combination
      with TENS treatment. The other 15 patients (third group) experienced low
      frequency (2 Hz) TENS for two weeks. RESULTS: There was no statistically
      significant difference in severity and number of withdrawal symptoms between the
      3 groups prior to the start of treatments. But, severity and number of symptoms
      were significantly higher in TENS group (third group) in third day. In addition,
      10 patients of TENS-group left the treatment programme after 5 days. The results
      showed that methadone only and Methadone plus TENS for the management of opioid
      detoxification were effective treatments. The comparison of number and severity
      of withdrawal symptoms in the methadone group and methadone+TENS group by seventh
      day didn't show significant differences. But, number and severity of withdrawal
      symptoms in methadone+TENS group were significantly lower than methadone group
      during tenth and fourteenth days. CONCLUSION: The results provide support for the
      use of methadone alone and methadone plus TENS for managing opiate withdrawal,
      but TENS by itself has no significant effect on withdrawal symptoms. However,
      TENS in combination with a moderate dose of methadone could reduce severity of
      withdrawal symptoms effectively.

PMID- 19157320
TI  - Association between health-related quality of life and children's unintentional
      injuries.
AB  - OBJECTIVE: To examine the association between health-related quality of life
      (HRQOL) and unintentional injuries among children. METHODS: Overall, 3375
      children aged 6-10 years were randomly selected from primary schools in Iran.
      HRQOL was measured by 56 items taken from seven domains of TNO AZL child quality
      of life (TACQOL) parent form. Parents were interviewed to collect information
      about incidence, cause and a brief description of injury within the past 12
      months prior to the study. RESULTS: The response rate was 3375 of 3792 (89%).
      There was a significant trend for increasing occurrence of injury with decreasing
      of HRQOL (P<0.001). Adjusted OR for injury was significantly higher in very low
      (2.38, 95% CI: 1.45-3.86), low (2.18, 95% CI: 1.34-3.56), medium (1.73, 95%CI:
      1.06-2.83) HRQOL groups compared to reference group (very high HRQOL). The median
      of total HRQOL (P<0.001) and all its domains (P=0.017) (except autonomous
      functioning) was less in injured group compared to the uninjured one. CONCLUSION:
      This study found an association between HRQOL and unintentional injury among
      primary schoolchildren. This is a preliminary finding and so further
      investigations with a well-defined analytical design needs to be done.

PMID- 19157321
TI  - Practices and knowledge of schoolchildren regarding chhaalia/paan masala in
      Mahmoodabad and Chanesar Goth, Karachi.
AB  - OBJECTIVE: To determine the practices and knowledge about chhaalia and paan
      masala chewing among school children in Mahmoodabad and Chanesar Goth, Karachi,
      Pakistan. METHODS: A cross-sectional study was conducted in three government
      schools of Mahmoodabad and Chanesar Goth, Jamshed Town, Karachi. Students of
      either gender were interviewed using a pre-coded structured questionnaire. In
      addition to the demographic data, questions included frequency of use, practices
      among friends and family and procurement of these substances. Knowledge about
      harmful effects, source of the knowledge and practices in relation to knowledge
      were also assessed. RESULTS: A total of 370 students, ages between 10 to 15 years
      were interviewed, of which 205 (55.4%) were boys. Thirty one percent of fathers
      and 62% of mothers were uneducated. The frequency of using chhaalia was 94% and
      that of paan masala was 73.8%, with 85% being regular users and 95% had friends
      with similar habits. Majority (88%) procured the substances near their homes,
      chhaalia was considered harmful for health by 96% and Paan Masala by 60% of the
      students. The commonest reason for continuing use was good taste (88.5%) followed
      by company of friends (57%). Knowledge about harmful effects was adequate in both
      "daily" and "less than daily users". CONCLUSION: The frequency of chhaalia and
      paan masala chewing, among school children in lower socio-economic areas is high.
      The probable reasons might be the taste, widespread use of these substances by
      family members and friends, low cost and easy availability. Although knowledge
      about harmful effects of these habits was adequate, but very little students knew
      about Oral Submucous Fibrosis (OSMF).

PMID- 19157322
TI  - Late cardiotoxic effects of anthracycline chemotherapy in childhood malignancies.
AB  - OBJECTIVE: To determine the frequency of changes in left ventricular function in
      patients, at least 5 years after completion of anthracycline-therapy for
      childhood malignancy. METHODS: Echocardiographic examination was performed on 58
      patients (36 males and 22 females) with mean age of 17.5+/-4.6 years (range 9-29
      years, median 17.5 years). The control group was 58 healthy age and sex matched
      children. RESULTS: The age at the time of diagnosis and start of treatment ranged
      from 2 to 14 years with a median of 6 years. The time of follow-up was between 5
      to 22 years with a median of 9 years. The cumulative dose of anthracycline was 30
      to 557 mg/m2, median 128.5 mg/m2. All the patients were asymptomatic. Abnormal
      systolic and/or diastolic functions were found in 29 (50%) patients. We found a
      strong correlation between systolic and diastolic cardiac dysfunction and longer
      time of follow-up (P = 0.02 and p = 0.04), respectively, but not a relation to
      the cumulative dose, sex, and age at diagnosis. CONCLUSION: The data showed a
      relatively high incidence of subclinical cardiotoxicity in long-term survivors.
      The significance of this subclinical cardiotoxicity on the morbidity and
      mortality of patients should be followed in the future.

PMID- 19157323
TI  - Dietary habits and life style among the students of a private medical university
      Karachi.
AB  - OBJECTIVES: To determine the dietary habits and life style of the students of a
      private medical university in Karachi. METHODOLOGY: A cross-sectional study was
      conducted at Baqai Medical University, from August 2005 to September 2005. A
      total of 384 medical students from the batches of 2002 to 2005 participated in
      this study. A pre-tested semi structured questionnaire was self administered to
      the students after taking their consent. The data included socio-demographic
      characteristics, life style, exercise, dietary habits and family history of
      diabetes mellitus. The collected data was analyzed by statistical program SPSS
      version 11. RESULTS: Out of the total participants, 53.4% were male and 46.6%
      were female students. The mean age was 20 +/- 1.58 years. The average income of
      the household of students was 50,000 Pakistani rupees per month. Only 7% students
      were tobacco users. About 33% students had a history of diabetes mellitus among
      their parents. Nearly 97% reported consumption of junk food while 60% reported
      use of whole grain food in their diet. Seventy percent students walked 30 minutes
      and 47% exercised daily. According to the body mass index, 58.3% students were of
      normal weight and 41.7% were overweight. No significant difference was found
      among male and female students when dietary habits and life style were compared
      by sex. Junk food and soft-drink consumption was associated with being
      overweight. Eating whole grain food and doing exercise showed a protective
      association against overweight. CONCLUSION: Unhealthy lifestyle and poor dietary
      habits were highly prevalent in the overweight study population. Type-2 diabetes
      mellitus was common among parents and grandparents of the students making them
      prone to this disorder. Our study concluded that dietary and exercise counselling
      is necessary as a preventive strategy.

PMID- 19157324
TI  - Use of anticonvulsants drugs for neuropathic painful conditions.
AB  - Neuropathic pain, a form of chronic pain initiated and sustained by an insult to
      the peripheral or central nervous system, is a challenge to clinicians as it does
      not respond well to traditional pain therapies. However exact pathophysiology is
      not known but considering similarities between epilepsy models and in neuropathic
      pain models justify the rationale for use of anticonvulsant drugs in the
      symptomatic management of neuropathic pain disorders. The role of anticonvulsant
      drugs in the treatment of neuropathic pain is evolving and various clinical
      trials have used these anticonvulsants and shown positive results in the
      treatment of trigeminal neuralgia, painful diabetic neuropathy and postherpetic
      neuralgia. The availability of newer anticonvulsants tested in higher quality
      clinical trials has marked a new era in the treatment of neuropathic pain.
      Gabapentin has the most clearly demonstrated analgesic effect for the treatment
      of neuropathic pain, specifically for treatment of painful diabetic neuropathy
      and postherpetic neuralgia. Pregablin is a newer drug and will soon gain
      popularity in clinical practice. There is a need for further advances in our
      understanding of the neuropathic pain syndromes to establish the role of
      anticonvulsants in the treatment of neuropathic pain.

PMID- 19157325
TI  - Response of Imitanib Meysylate in patients with gastrointestinal stromal cell
      tumour.
AB  - In this study, the response of Imitanib Mesylate in patients with Gastro
      intestinal stromal cell tumour (GIST) was assessed. GIST results from a mutation
      in one of the receptor protein tyrosine kinases. Imitanib Mesylate, a tyrosine
      kinase inhibitor, has emerged as a promising new treatment for GISTs. Total 16
      cases were reviewed. Diagnosis was based on biopsy and immunohistochemistry.
      Response assessment was done using CT scans, at a median duration of 4 months.
      The median age of the patients was 52 years, Majority were male (n=14). Most
      common presenting complaint was abdominal pain (n=7). Commonest primary site was
      stomach (n=7), Liver was the most common organ involved in metastasis (n=8). All
      patients received Imitanib 400 mg orally, once a day. No mortality was reported
      during median follow up time of 28 months on Imitanib. There was also either
      radiological remission (n=5) or response (n=5), in about half of the patients
      without any serious side effects.

PMID- 19157326
TI  - Learning procedures during house job.
AB  - House job is the important year of the clinical experience under supervision
      before the start of the own practice as a phsician. It is understood that
      clinical experience of new medical graduates are poor and they are expected to
      learn clinical skills by one year house job experience. Hence there is need to
      asess the basic clinical skills competency. A questionnaire was given to thirty
      house officers regrding the ten basic clinical procedures which are expected from
      all of them to learn and carry out independently till the end of their house
      jobs. They were asked to fill it up according to their competency level at the
      beginning and end of their jobs. The purpose of the study was to assess the
      competency level of the house officers individually which will provide
      information to the supervisors what needs attention so that remedial action can
      be taken in time. This study was undertaken to find out how much confidence the
      house officers acquire during house job in carrying out specified procedures.

PMID- 19157327
TI  - Ganglioneuroma of the neck.
AB  - Ganglioneuroma (GN) has a neuroectodermic origin and is localized along the
      sympathetic trunk. GN of the neck is a rare tumour and due to proximity to the
      thyroid gland, clinically and radiologically, these lesions can be mistaken as
      thyroid swellings. Definite diagnosis only can be suspected after surgical
      exploration and complete surgical excision is the treatment of choice, as it will
      ensure thorough sampling of the tumour and cure.

PMID- 19157328
TI  - Recurrent priapism in sickle cell trait with protein S deficiency.
AB  - We report the case of a young Omani man, a regular blood donor, who presented
      twice in two months, with painful penile erection lasting more than 12 hours. The
      patient is known to have sickle cell trait [HbS 34.6%]. Although the first
      episode of penile erection settled with aspiration of blood and local injection
      of epinephrine, on the second occasion necessitated cavernosal glandular
      shunting. A subsequent investigation revealed a mild protein S deficiency.
      Although priapism is known to occur in sickle cell disease, it is unusual in
      sickle cell trait. Association of mild protein S deficiency with erythrocytosis
      could have precipitated the onset of priapism.

PMID- 19157329
TI  - Reactive thrombocytosis with digital gangrene.
AB  - Patients with reactive thrombocytosis are generally asymptomatic and platelet
      counts of up to 1,000,000/microL are seen in this disorder. However, in a small
      proportion of cases platelet counts may be in the range generally seen in Clonal
      Thrombocytosis (CT). In elderly patients or those with symptomatic
      atherosclerosis or thrombotic disease or immobility, thrombosis may occur even
      with reactive thrombocytosis. We report a case of a rare presentation of Reactive
      Thrombocytosis with digital gangrene in an elderly lady. She was evaluated for
      thrombocytosis and was given supportive treatment after which she clinically
      improved.

PMID- 19157330
TI  - Castleman's disease of the duodenum.
AB  - Castleman's disease is a rare lymphoproliferative disorder of uncertain origin.
      Just two cases of Castleman's disease of the gastrointestinal tract have been
      reported. These were found in the stomach. However, as far as we know,
      Castleman's disease of the duodenum has not been reported. This is the first
      report of hyaline vascular subtype of Castleman's disease at the duodenum.

PMID- 19157332
TI  - Closure of patent ductus artriosus by transcatheter technique in a pregnant
      patient.
AB  - We report a case of Patent ductus arteriosus (PDA), which was closed successfully
      by transcatheter technique in a pregnant patient. This procedure was safe,
      effective and uncomplicated, obviating the need for surgery in this high risk
      patient.

PMID- 19157331
TI  - Adult unilateral supraglottitis as a consequence of acute submandibular
      sialadentis.
AB  - Acute Submandibular sialadenitis (ASS) may spread to sublingual and submandibular
      spaces. On rare occasions it can spread along the floor of the mouth, to the base
      of the tongue and to the pre epiglottic space, valleculae and epiglottis, leading
      to supraglottitis. Adult supraglottitis is an acute inflammation of the
      supraglottic structures. Unilateral supraglottitis in an adult as a consequence
      of ASS is a unique complication as described in this case report. Sore throat
      with severe odynophagia and tachycardia were the early warning signs. Early
      suspicion, prompt airway management, antibiotics, proper rehydration and
      analgesics are the mainstay of treatment.

PMID- 19157333
TI  - Aftermath of child abuse: need to reduce the burden of morbidity.

PMID- 19157334
TI  - Awareness of the risk factors, presenting features and complications of
      hypertension amongst hypertensives and normotensives.
AB  - OBJECTIVES: To assess the level of awareness with regards to risk factors,
      presenting features and complications of hypertension. Moreover, to Compare the
      level of awareness amongst patients (hypertensives) and nonpatients
      (normotensives) in Karachi, Pakistan. METHODS: This cross-sectional study was
      carried out on a random sample of 440 people (220-normotensives/220
      hypertensives) using an interview based questionnaire. Data entry was performed
      on Epi-info v 6 and managed and analyzed on SPSS v 14. Proportions were
      calculated for categorical data, means and standard deviations were calculated
      for continuous data. RESULTS: Hypertensives had a higher mean awareness score
      than the normotensives (p<0.001). It was observed that people below 30 years of
      age were significantly more aware than people above this age (p<0.001). Patients
      with higher awareness scores were more compliant to therapy (p<0.001).
      CONCLUSION: Poor levels of awareness regarding the risk factors, presenting
      features and complications of hypertension were observed in both the groups. The
      hypertensive population was relatively more aware than the normotensive
      population.

PMID- 19157335
TI  - Multiple lead pellets in scalp.

PMID- 19157336
TI  - Prevalence and correlates of tobacco use among class 8 to 10 students in
      Islamabad and Lahore.

PMID- 19157337
TI  - Uterine artery Doppler ultrasonography in the first and second trimester for
      prediction of preeclampsia: implications for Pakistan.

PMID- 19157338
TI  - The introduction of blood pressure monitoring into anaesthesia.

PMID- 19157339
TI  - You only find what you look for: the importance of high creatinine clearance in
      the critically ill.

PMID- 19157340
TI  - Risk factors for post-pneumonectomy acute lung injury/acute respiratory distress
      syndrome in primary lung cancer patients.
AB  - Acute lung injury/acute respiratory distress syndrome (ALI / ARDS) is the most
      serious pulmonary complication after lung resection. This study investigated the
      incidence and outcome of patients with ALI / ARDS who required mechanical
      ventilation within one week of undergoing pneumonectomy for primary lung cancer
      and analysed the risk factors. We retrospectively reviewed the medical records of
      146 patients who underwent pneumonectomy for primary lung cancer between May 2001
      and April 2006. Preoperative, perioperative and postoperative clinical data were
      analysed. Post-pneumonectomy ALI / ARDS developed within the first postoperative
      week in 18 (12%) patients. Patients who developed ALI / ARDS had a longer
      hospital duration of stay (median [interquartile range], 26 [18 to 75] vs. 8 [7
      to 11] days; P < 0.001) and higher in-hospital mortality (12 [67%] vs. 0 [0%]; P
      < 0.001). In an univariate analysis, post-pneumonectomy ALI / ARDS was associated
      with larger tidal volume (V(T)) and higher airway pressure (P(aw)) during one
      lung ventilation (V(T) 8.2 [7.5 to 9.0] vs. 7.7 [6.9 to 8.2] ml/kg predicted body
      weight, P = 0.016; P(aw), 28.9 [27.6 to 30.0] vs. 27.2 [25.6 to 28.5] cmH2O, P =
      0.001). V(T) during two-lung ventilation was also greater in patients who
      developed ALI / ARDS (P = 0.014) than in those who did not, but P(aw) during two
      lung ventilation did not differ (P = 0.950). In a multiple logistic regression
      analysis, post-pneumonectomy ALI / ARDS was independently associated with a
      larger V(T) (OR 3.37 per 1 ml/kg predicted body weight increase; 95% confidence
      interval 1.65 to 6.86) and higher P(aw) (OR 2.32 per 1 cmH2O increase; 95%
      confidence interval 1.46 to 3.67) during the period of one-lung ventilation. In
      conclusion, a large V(T) and high P(aw) during one-lung ventilation were
      associated with an increased risk of post-pneumonectomy ALI / ARDS in primary
      lung cancer patients.

PMID- 19157341
TI  - Changes in serum procalcitonin and C-reactive protein following antimicrobial
      therapy as a guide to antibiotic duration in the critically ill: a prospective
      evaluation.
AB  - Serial procalcitonin is reported to be useful to titrate duration of antibiotic
      therapy in the non critically ill patient with pneumonia. The aim of this study
      was to examine the relationship between antibiotic therapy and serial serum
      procalcitonin concentrations in a cohort of critically ill septic patients and
      examine for any differences between culture positive (CP) and culture negative
      (CN) sepsis. Seventy-five critically ill patients with suspected sepsis were
      enrolled in this prospective observational study. Serial procalcitonin and C
      reactive protein assays were measured on days one, three, five, seven, 10 and 14.
      The mean duration of antibiotic therapy was similar in the two groups (10.4 +/-
      5.1 (CP) vs. 8.4 +/- 5.1 (CN) days, P = 0.09). Serum procalcitonin concentrations
      were significantly higher at baseline in the CP than the CN group (14.9 +/- 22.9
      vs. 6.8 +/- 21.5 ng/ml, P = 0.04). During the study period, serum concentrations
      of procalcitonin and C-reactive protein declined in both groups. Serum
      procalcitonin consistently remained higher in the CP group (P < 0.05) and did not
      return to normal values. In the CN group, procalcitonin concentrations fell below
      0.5 only on day 10. There was no significant difference in C-reactive protein
      profile between the two groups. Four patients in the CP group (11%) had relapse
      of sepsis. The mean procalcitonins in the relapsed subgroup were lower than those
      in the remission subgroup (P = 0.02). Therapy for proven or presumed infections
      was associated with declining serum procalcitonin and C-reactive protein in
      critically ill septic patients. The marked variability and overlap in plasma
      profile of these markers between CP and CN sepsis makes it difficult to define a
      nadir plasma concentration at which one can recommend discontinuation of
      antibiotic therapy.

PMID- 19157342
TI  - Dose-related effect of propofol on pancreatic enzymes and triglyceride levels in
      patients undergoing non-abdominal surgery.
AB  - Various case reports have indicated a possible relationship between propofol and
      pancreatitis. However, it is not clear whether this relationship (if any) is dose
      related or idiosyncratic. Therefore, a prospective study was conducted to
      evaluate the effect of different doses of propofol on postoperative pancreatic
      enzymes and serum triglyceride levels. One hundred and fifty patients, aged 18 to
      60 years, belonging to ASA physical status I and II, undergoing non-abdominal
      surgery were divided into three groups. Anaesthesia was induced with propofol 2
      to 2.5 mg/kg in all groups. It was maintained with isoflurane in group I,
      propofol infusion < 5 mg/kg/h in group II and propofol infusion > or = 5 mg/kg/h
      in group III. All three groups also received nitrous oxide in oxygen for
      maintenance of anaesthesia. Serum amylase, lipase and triglyceride were estimated
      before propofol administration and at 24 and 72 hours postoperatively. The mean
      values of serum amylase, lipase and triglyceride remained within the normal range
      in the three groups. These values did not differ significantly in between the
      groups even despite the significantly different doses of propofol in the three
      groups (P < 0.001). None of the patients in the three groups developed any
      feature suggestive of acute pancreatitis in the postoperative period. These
      findings indicate that propofol administration at recommended doses does not
      produce dose-related increases in pancreatic enzyme and triglyceride levels in
      ASA physical status I and II patients.

PMID- 19157343
TI  - A prospective randomised controlled trial of ultrasound guided versus nerve
      stimulation guided distal sciatic nerve block at the popliteal fossa.
AB  - The direct visualisation of nerves and adjacent anatomical structures may make
      ultrasonography the preferred method for nerve localisation. In this prospective
      randomised study, we investigated whether, for distal sciatic nerve block in the
      popliteal fossa, an ultrasound guided technique would result in the use of less
      local anaesthetic without changing block characteristics and quality. Using
      electrical nerve stimulation or ultrasound guidance, the nerve was identified in
      two groups of 20 patients scheduled for lower limb surgery. Hereafter lignocaine
      1.5% with adrenaline 5 microg/ml was injected. The attending anaesthesiologist
      assessed the injected volume. Significantly less local anaesthetic was injected
      in the ultrasound group compared to the nerve stimulation group (17 vs. 37 ml, P
      < 0.001), while the overall success rate was increased (100% vs. 75%; P = 0.017).
      We conclude that the use of ultrasound localisation for distal sciatic nerve
      block in the popliteal fossa reduces the required dose of local anaesthetic
      significantly, and is associated with a higher success rate compared to nerve
      stimulation without changing block characteristics.

PMID- 19157344
TI  - APOE genotype affects outcome in a murine model of sepsis: implications for a new
      treatment strategy.
AB  - In this study, we assessed whether apolipoprotein E (APOE) polymorphism affects
      inflammatory responses and mortality in the caecal ligation and puncture model of
      peritonitis. In addition, we determined the effects of APOE mimetic peptide
      administration in this sepsis model. Differences in survival between targeted
      replacement mice expressing the human APOE3 allele (APOE3TR) and the APOE4 allele
      (APOE4TR) mice were assessed. In a separate series of experiments, COG1410, an
      apoE-mimetic peptide, was administered intravenously at 12-hour intervals for 72
      hours and compared to vehicle-treated control animals. End-points included
      mortality and serum levels of interleukin-1beta, interleukin-6, interleukin-12
      and tumour necrosis factor-alpha. Mice expressing the human APOE4 allele (n = 16)
      demonstrated an increase in mortality following caecal ligation and puncture
      compared with APOE3TR mice (n = 22; P = 0.039). Administration of the
      apolipoprotein E mimetic COG1410 was well tolerated and APOE3TR mice treated with
      peptide (n = 20) demonstrated a significant reduction in mortality compared with
      vehicle treated animals (n = 20; P = 0.007). A similar effect was also observed
      in APOE4TR animals, in which treatment with COG1410 was associated with reduced
      mortality compared with vehicle treatment (n =16 animals/group; P = 0.027).
      COG1410 was also associated with a reduction in TNFalpha, interleukin-1beta,
      interleukin-6 and interleukin-12 levels in both APOE3TR and APOE4TR (n = 5
      animals/group) assessed at 24 hours. Thus, administration of an apolipoprotein E
      mimetic peptide is well tolerated, suppresses inflammatory responses, and
      improves mortality in a caecal ligation and puncture model of sepsis.

PMID- 19157345
TI  - Comparison of computer-integrated patient-controlled epidural analgesia and
      patient-controlled epidural analgesia with a basal infusion for labour and
      delivery.
AB  - Computer-integrated patient-controlled epidural analgesia (CIPCEA) is a novel
      epidural drug delivery system. It automatically adjusts the background infusion
      based on the individual parturient's need for analgesia as labour progresses. In
      this randomised controlled trial, we compared the local anaesthetic consumption
      by parturients using either CIPCEA or patient-controlled epidural analgesia with
      a moderate basal infusion (PCEABI) of 5 ml/hour. We recruited 60 parturients
      after receiving ethics committee approval. Group CIPCEA (n = 30) received a
      similar patient-controlled epidural analgesia regimen but the computer
      integration titrated the background infusion to 5, 10 or 15 ml/hour if the
      patient required respectively one, two or three demand boluses in the previous
      hour. The background infusion was decreased by 5 ml/hour if there was no demand
      in the previous hour. Group PCEABI received patient-controlled epidural analgesia
      with a basal infusion of 5 ml/hour. The sample size was calculated to show
      equivalence in local anaesthetic use. The time-weighted consumption of local
      anaesthetic was similar in both groups (mean difference 0.3 mg/hour 95%
      confidence interval: -1.8, 1.3, P = 0.755). The CIPCEA group had higher maternal
      satisfaction scores: mean (SD) 94.8 (6.32) vs. 85.5 (9.41), P = 0.0001. The
      CIPCEA group had a higher infusion rate during the second stage of labour (mean
      (SD) 7.0 (4.1) ml/hour vs. 4.5 (1.5) ml/hour P = 0.008), but did not have a
      longer duration of this stage. There were no differences between the groups in
      obstetric or foetal outcomes or side-effect profiles. The CIPCEA system has
      similar time-weighted, hourly consumption of local anaesthetic to PCEABI and may
      increase patient satisfaction.

PMID- 19157346
TI  - Tropisetron plus subhypnotic propofol infusion is more effective than tropisetron
      alone for the prevention of vomiting in children after tonsillectomy.
AB  - This study evaluated the efficacy of tropisetron compared with tropisetron and a
      subhypnotic propofol infusion in preventing postoperative vomiting following
      tonsillectomy. One hundred and forty healthy children, aged four to 12 years,
      undergoing tonsillectomy were recruited in a randomised, double-blind study.
      After induction with sevoflurane, anaesthesia was maintained with sevoflurane and
      nitrous oxide. All patients received tropisetron (0.2 mg/kg up to 5 mg;
      intravenously) and fentanyl (2 microg/kg; intravenously) and were intubated after
      atracurium which was reversed with neostigmine (and atropine). The tropisetron
      plus-propofol group received a single dose of propofol (1 mg/kg) before
      intubation and a continuous infusion of propofol throughout surgery at 15
      microg/kg/min. Data for postoperative vomiting were grouped into zero to four and
      four to 24 hour time intervals. A P value of < 0.05 was considered statistically
      significant. The percentage of patients exhibiting a complete response (no
      retching or vomiting for 24 hours) was 47.1% (33/70) in the tropisetron-alone
      group and 72.8% (51/70) in the tropisetron-plus-propofol group (P = 0.002). The
      0.257 absolute risk reduction of vomiting with the addition of propofol
      represents a number needed to treat of 3.87, and a risk ratio of 0.51 (95% CI
      0.32 to 0.79). Significantly fewer patients vomited in the tropisetron-plus
      propofol group than in the tropisetron-alone group during the zero to four post
      surgery interval (P = 0.016), but the difference was not statistically
      significant for the four to 24 hour postoperative period (P = 0.116).
      Intraoperative subhypnotic propofol infusion combined with tropisetron is more
      effective than tropisetron alone in reducing postoperative vomiting after
      tonsillectomy in children.

PMID- 19157347
TI  - A new degraded auditory stimulus test to measure implicit memory during
      anaesthesia in children.
AB  - It remains unclear whether children form implicit memories during general
      anaesthesia. This is partly due to a lack of tests for implicit memory that are
      appropriate for the anaesthesia setting. The aim of this study was to assess a
      new implicit memory test that could be more suitable for use with children during
      anaesthesia. Ninety-three children aged five to 12 years who were undergoing
      elective surgery were studied. Patients were randomly assigned to one of two
      groups preoperatively and exposed to a familiar animal sound, followed by a
      distractor task. Two animal sounds were tested; in one group children were
      exposed to one animal sound preoperatively, while in the other group they were
      exposed to the other. After surgery the children were played degraded versions of
      the animal sounds that had been mixed with white noise and became increasingly
      clearer over the 60 second recording. Children who explicitly recalled hearing
      the sound preoperatively were excluded. Response times for recognition were
      recorded and compared. The analysis revealed evidence for a significant priming
      effect for one of the two animal sounds tested. The speed and simplicity of
      administration of this test suggest the degraded auditory stimulus test would be
      a promising tool to detect implicit memory during anaesthesia in children.
      However as we found evidence for priming with only one of the sounds, the choice
      of sound is important.

PMID- 19157348
TI  - Antibacterial activity of epidural infusions.
AB  - The incidence of epidural abscess following epidural catheterisation appears to
      be increasing, being recently reported as one in 1000 among surgical patients.
      This study was designed to investigate the antibacterial activity of various
      local anaesthetics and additives, used in epidural infusions, against a range of
      micro-organisms associated with epidural abscess. The aim was to determine which,
      if any, epidural infusion solution has the greatest antibacterial activity.
      Bupivacaine, ropivacaine and levobupivacaine crystals were dissolved and added to
      Mueller-Hinton Agar in concentrations of 0.06%, 0.125%, 0.2%, 0.25%, 0.5% and 1%.
      Fentanyl, adrenaline and clonidine were also mixed with agar in isolation and in
      combination with the local anaesthetics. Using a reference agar dilution method,
      the minimum inhibitory concentrations were determined for a range of bacteria.
      Bupivacaine showed antibacterial activity against Staphylococcus aureus,
      Enterococcus faecalis and Escherichia coli with minimum inhibitory concentrations
      between 0.125% and 0.25%. It did not inhibit the growth of Pseudomonas aeruginosa
      at any of the concentrations tested. Levobupivacaine and ropivacaine showed no
      activity against Staphylococcus aureus, Enterococcus faecalis and Pseudomonas
      aeruginosa, even at the highest concentrations tested, and minimal activity
      against Escherichia coli (minimum inhibitory concentrations 0.5% and 1%
      respectively). The presence of fentanyl, adrenaline and clonidine had no
      additional effect on the antibacterial activity of any of the local anaesthetic
      agents. The low concentrations of local anaesthetic usually used in epidural
      infusions have minimal antibacterial activity. While the clinical implications of
      this in vitro study are not known, consideration should be given to increasing
      the concentration of bupivacaine in an epidural infusion or to administering a
      daily bolus of 0.25% bupivacaine to reduce the risk of epidural bacterial growth.

PMID- 19157349
TI  - Dose requirements for propofol anaesthesia for dental treatment for autistic
      patients compared with intellectually impaired patients.
AB  - We had clinical grounds to suspect that patients with autism had greater propofol
      requirements during dental procedures than patients with intellectual impairment
      without autism. This hypothesis was tested by an audit of a standard anaesthetic
      technique. The audit was approved by our Hospital Ethics Committee. We compared
      the propofol requirements and effect using a standardised protocol during dental
      treatment in 56 autistic patients (age range three to 35 years) and 56
      intellectually impaired patients (age range four to 42 years). Patients in each
      disability group were divided into three subgroups by age: six years or younger,
      seven to 19 years and 20 years or older. Combative patients received oral
      midazolam premedication, other patients received a single intravenous bolus of
      midazolam at induction. Otherwise, standardised propofol boluses and infusion
      were the only anaesthetic agents used. The propofol infusion rates of the
      intellectually impaired group showed significant decline with age (propofol rate
      of requirement mg x kg(-1) x h(-1), mean [SD]): < six years 13.6 (3.6), seven to
      19 years 9.5 (3.0) (P = 0.008 cf < six years group), > 19 years group 8.5 (2.4)
      (P = 0.001 cf < six years group). The propofol requirement was greater in the
      autism group than in the intellectual disability group, and the proportion of the
      cases where bolus propofol administration was needed after induction was
      significantly higher in the autistic patient group than in the intellectually
      impaired patients (P < 0.002). This suggests that autistic patients have greater
      propofol requirements for anaesthesia during ordinary dental treatment compared
      with intellectually impaired patients.

PMID- 19157350
TI  - In situ simulation-based team training for post-cardiac surgical emergency chest
      reopen in the intensive care unit.
AB  - Emergency chest reopen of the post cardiac surgical patient in the intensive care
      unit is a high-stakes but infrequent procedure which requires a high-level team
      response and a unique skill set. We evaluated the impact on knowledge and
      confidence of team-based chest reopen training using a patient simulator compared
      with standard video-based training. We evaluated 49 medical and nursing
      participants before and after training using a multiple choice questions test and
      a questionnaire of self-reported confidence in performing or assisting with
      emergency reopen. Both video- and simulation-based training significantly
      improved results in objective and subjective domains. Although the post-test
      scores did not differ between the groups for either the objective (P = 0.28) or
      the subjective measures (P = 0.92), the simulation-based training produced a
      numerically larger improvement in both domains. In a multiple choice question out
      of 10, participants improved by a mean of 1.9 marks with manikin-based training
      compared to 0.9 with video training (P = 0.03). On a questionnaire out of 20
      assessing subjective levels of confidence, scores improved by 3.9 with manikin
      training compared to 1.2 with video training (P = 0.002). Simulation-based
      training appeared to be at least as effective as video-based training in
      improving both knowledge and confidence in post cardiac surgical emergency
      resternotomy.

PMID- 19157351
TI  - The evaluation of anaesthesia-related information on the Internet.
AB  - The quality and accessibility of anaesthesia-related information available to
      patients on the Internet is a growing concern for the specialty. We sought to
      evaluate the quality of anaesthesia-related websites using a simple scoring
      system. The scoring system comprised quality and technical scores individually,
      and these were also combined into a total score. Test-retest reliability was
      assessed by calculating intraclass correlation coefficients. We employed the four
      most popular search engines and one meta-search engine, using the search term
      "general anaesthesia". Only the first 10 sites retrieved were scored. The
      intraclass correlation coefficients for all terms demonstrated at least moderate
      agreement and the total scores demonstrated high consistency r = 0.852, 0.774 (P
      < 0.001, and P < 0.003 respectively). There were 18 duplicate websites and 32
      were scored. There was no difference between search engines for any of the three
      scores awarded. The majority of websites were rated as either 'poor' or fair'
      across all scores. Our study indicates that quality anaesthesia-related
      information is unlikely to be retrieved by patients using the Internet.

PMID- 19157352
TI  - Randomised comparison of the Classic Laryngeal Mask Airway with the Cobra
      Perilaryngeal Airway during anaesthesia in spontaneously breathing adult
      patients.
AB  - We tested the hypothesis that the Cobra Perilaryngeal Airway (PLA) with its high
      volume low-pressure cuff would provide superior airway leakage pressure compared
      with the Classic Laryngeal Mask Airway (LMA) in spontaneously breathing adult
      patients. Ninety consecutive adult patients were randomly allocated to receive
      one of these two supralaryngeal devices. The airway leakage pressure was higher
      for the PLA compared with the LMA (22 +/- 9 cmH2O vs. 18 +/- 6 cmH2O; P < 0.05).
      The mean airway device intracuff pressure was lower for the PLA compared to the
      LMA (36.1 +/- 15.2 mmHg vs. 86.3 +/- 25.3 mmHg P < 0.0001). The time required to
      achieve successful insertion was greater for the PLA compared with the LMA (39 +/
      21 seconds vs. 27 +/- 10 seconds; P < 0.005). The number of attempts required to
      achieve successful insertion and the incidence of postoperative complications
      were similar in both groups. The findings suggest that the PLA provides a
      superior airway seal at a lower intracuff pressure compared to the LMA. However
      the time for successful insertion may be increased.

PMID- 19157353
TI  - Drug administration errors: a prospective survey from three South African
      teaching hospitals.
AB  - This prospective study was undertaken to determine the incidence of drug
      administration errors by anaesthetists at three tertiary South African hospitals.
      Hospitals A and C treat adults predominantly, whereas Hospital B is a paediatric
      hospital. Anaesthetists completed an anonymous study form for every anaesthetic
      performed over a six-month period. They were asked to indicate whether or not an
      error or near-miss had occurred and if so, the details thereof. A total of 30,412
      anaesthetics were administered during the study period. The response rate and
      combined incidence of errors and near-misses was as follows: Hospital A 48.8%
      (1:320), B 81.3% (1:252) and C 48.1% (1:250). The overall response rate was 53%
      and the combined incidence was 1:274. Neither the experience of the anaesthetist
      nor emergency surgery influenced whether an error occurred or not. Most errors
      occurred during the maintenance phase of anaesthesia. The most common errors were
      those of substitution. At the paediatric hospital, incorrect dose was as frequent
      an error as substitution. Of all errors, 36.9% were due to drug ampoule
      misidentification; of these the majority (64.4%) were due to similar looking
      ampoules. Another 21.3% were due to syringe identification errors. No major
      complication attributable to a drug administration error was reported. Despite an
      increasing awareness of the problem together with suggestions in the literature
      to reduce the incidence, drug administration errors remain fairly common in South
      Africa. Failure to institute suggested solutions will continue to compromise
      patient safety.

PMID- 19157354
TI  - Ventilation and weaning practices in Australia and New Zealand.
AB  - Using a one-day prospective point prevalence design, this study aimed to
      characterise the current practice of mechanical ventilation and weaning in
      Australian and New Zealand intensive care units. During 2005, a bi-national one
      day survey of 55 intensive care units found the point-prevalence of mechanical
      ventilation to be 284/491(58%). Common modes used were synchronised intermittent
      mandatory ventilation with pressure support, pressure support ventilation (each
      116/284, 41%) and pressure-control modes (48/284, 17%). Relative to volume
      control modes, pressure-control was more frequently used for patients with
      respiratory disease (odds ratio 4.7, 95% confidence interval 2.4 to 9.2, P
      <0.001) or greater severity of illness (odds ratio 1.7, 95% confidence interval
      1.1 to 2.6, P = 0.01, per five-point increment in the maximum sequential organ
      failure score). Excluding cardiothoracic surgery patients, the Kaplan-Meier
      estimated median total ventilation duration was 1.9 days (interquartile range 0.8
      to 6.8 days). Apart from 24/255 (9.4%) patients who received only pressure
      support ventilation, weaning methods (attempted in 255 patients, 29 prior deaths)
      included: change to pressure support ventilation (186/255, 73%), T-piece (31/255,
      12%) or other methods (14/255, 5.5%). The point prevalence of mechanical
      ventilation was greater than comparable international studies. Australian and New
      Zealand intensive care unit ventilatory practices are similar, but differ
      substantially from published international survey results, due to a near absence
      of assist/control, prominent use of pressure-control modes and a preference
      forpressure support ventilation weaning as opposed to T-piece.

PMID- 19157355
TI  - A survey of anaesthetists' perspectives of communication in the operating suite.
AB  - We surveyed 222 anaesthetists attending a University of Western Australia
      conference (n = 110) and two public hospitals in Perth (n = 112) by anonymous
      questionnaire in March 2006 regarding communication issues in the operating
      suite. Forty-one percent (n = 92) responded. Questions concerned communication
      skills, experiences of good and poor communication and relationship to outcome,
      attitudes to music and communication courses. Stress in anaesthetists due to poor
      communication, staff naming practices, information on courses with communication
      content attended and attitudes to non-verbal communication were also surveyed.
      Anaesthetists' communication skills were self-rated as "very good" by 52% and
      "average" by 39% of respondents. It was strongly agreed that good verbal
      communication leads to better patient outcome (57%) and was important between
      surgeons and anaesthetists (76%). Regarding the current state of
      surgeon/anaesthetist communication, 25% (23/92) agreed this was acceptable, 33%
      (30/92) were undecided and 42% (39/92) regarded this as poor. Silence in theatre
      was generally not desired, 71% preferring background music. Ninety-nine percent
      of respondents believed good communication decreased stress and 89% felt
      personally stressed in situations where poor communication occurred. Email/text
      communication was not preferred to spoken language regarding case information.
      Sixty-four percent of respondents would attend a communications course
      voluntarily, with implementation of a compulsory communications course supported
      by 45%. Most anaesthetists surveyed used staff first names and 94% believed poor
      communication caused procedural delay. The data suggest that further work is
      required to improve communication in the stressful operating room environment,
      particularly at the surgeon/anaesthetist interface.

PMID- 19157356
TI  - Users' opinions on intensive care unit alarms--a survey of German intensive care
      units.
AB  - Monitoring of physiologic parameters in critically ill patients is associated
      with an enormous number of alarms, leading to reduced clinical value with high
      sensitivity but low specificity. To evaluate opinions of intensive care unit
      (ICU) staff on current monitoring we conducted a survey of German ICUs.
      Furthermore, the survey aimed to assess requirements and requests for future
      alarm systems. The survey was conducted between May 2006 and June 2007 on a
      randomised sample of German ICUs. Questionnaires with 24 partly closed-ended
      partly open-ended questions were posted. Of 915 letters, 274 (30%) from 185
      contacted ICUs were returned and evaluated. One hundred and sixty physicians, the
      majority (52%) working in a department of anaesthesiology, and 114 nurses
      returned the survey. Most responders (87%) estimated that less than 50% of
      current alarms result in clinical consequences (52% estimated less than 25%). We
      suggested trend alarms, smoothing of signals to reduce artefacts, generation of
      new combined alarms and integrative monitoring of different alarm systems as
      improvements of current ICU alarm systems, all of which were agreed to by the
      majority. Free text commentaries focused on the need for reducing alarms caused
      by artefacts and called for improvement of the monitor-user interfaces. Our
      survey demonstrates the dissatisfaction of clinical staff with the current alarm
      systems regarding alarm frequency and specificity in German ICUs, thereby
      confirming data raised in single institutions. ICU staff's acceptance for new
      alarm algorithms like signal extraction or detection of trends as a basis for
      smart monitoring appealed to the majority of users.

PMID- 19157357
TI  - Central pontine myelinolysis despite slow sodium rise in a case of severe
      community-acquired hyponatraemia.
AB  - The management of severe hyponatraemia is a challenging task for intensivists. It
      should be based on underlying pathophysiology, especially the duration of
      hyponatraemia (acute vs. chronic) and the presence or absence of severe
      neurologic symptoms. We describe a case of severe community-acquired
      hyponatraemia in which central pontine myelinolysis developed several days after
      discharge from the intensive care unit, despite a gradual increase of plasma
      sodium levels during the intensive care unit stay.

PMID- 19157358
TI  - The use of "ketofol" (ketamine-propofol admixture) infusion in conjunction with
      regional anaesthesia.
AB  - We present four patients in whom a "ketofol" (ketamine 200 mg and propofol 200
      mg) infusion was used in conjunction with regional anaesthesia. The patients were
      considered 'high risk' due to their medical condition or age. The ketofol proved
      safe and effective in all four cases. Advantages of this technique included
      analgesia, airway preservation, maintenance of spontaneous respiration,
      haemodynamic stability and rapid recovery.

PMID- 19157359
TI  - Superficial cervical plexus block combined with auriculotemporal nerve block for
      drainage of dental abscess in adults with difficult airways.
AB  - We report our use of a superficial cervical plexus block to manage three adults
      who presented for drainage of dental abscesses. All patients had difficult
      airways related to severe trismus (preoperative inter-incisor distance < or = 1.5
      cm). The first two patients, whose abcesses involved both the submandibular and
      submasseteric spaces, were managed with combined superficial cervical plexus and
      auriculotemporal nerve block. In a third patient, a superficial cervical plexus
      block alone was sufficient because the abscess was confined to the submandibular
      region. The blocks were successful in all three cases with minimal requirement
      for supplemental analgesia. We recommend the consideration of superficial
      cervical plexus block, and if necessary an auriculotemporal nerve block, for the
      management of selected patients with difficult airways who present for drainage
      of dental abcesses.

PMID- 19157360
TI  - Talc-induced interstitial pneumonitis with respiratory failure.
AB  - Talc is the most frequently used chemical agent to induce pleurodesis and
      complications after this procedure, usually benign and self-limiting, are
      resolved easily. Pneumonitis with acute respiratory distress after talc
      pleurodesis is a rare complication, it requires intensive treatment and may be
      fatal. We describe a patient who developed pneumonitis with bilateral
      interstitial infiltrates and respiratory distress after talc pleurodesis. This
      complication required the transfer of the patient into the intensive care unit
      and an aggressive treatment management. After an uneventful talc pleurodesis,
      close surveillance of the patient and a high index of suspicion are mandatory.

PMID- 19157361
TI  - Survival after massive hydroxychloroquine overdose.
AB  - Hydroxychloroquine overdose is infrequently reported and the majority of
      recommendations come from the greater experience with chloroquine poisoning. We
      report two cases of massive hydroxychloroquine poisoning (20 g in each case),
      both of which received advanced cardiac life support and a treatment regimen
      consisting of sodium bicarbonate, adrenaline and potassium. Both these patients
      survived beyond their initial rapid deterioration and cardiovascular collapse to
      be discharged from hospital without sequelae. These patients had the highest
      reported non-lethal serum concentrations (13.8 and 26.0 mg/l). They both
      demonstrated rapid recovery from a pre-arrest condition, following aggressive
      correction of electrolyte and pH disturbance and rapid distribution of the drug
      to peripheral tissues.

PMID- 19157362
TI  - Evaluation of oxygen therapy devices.

PMID- 19157363
TI  - Aprepitant for postoperative nausea and vomiting.

PMID- 19157364
TI  - Securing the Aintree Intubation Catheter.

PMID- 19157365
TI  - Dental loss related to an endotracheal tube.

PMID- 19157366
TI  - Cricothyroidotomy assisted airway access with provision for connection to
      standard anaesthesia connectors.

PMID- 19157367
TI  - An unusual cause of patient pain during regional anaesthesia.

PMID- 19157368
TI  - Accidental bladder puncture: a complication of a modified fascia iliaca block.

PMID- 19157369
TI  - Lumbar canal stenosis: retrospective diagnosis after a high spinal block.

PMID- 19157370
TI  - Caesarean delivery under general anaesthesia for a woman with undiagnosed
      tuberous sclerosis complex and lymphangioleiomyomatosis.

PMID- 19157371
TI  - Ultrasound-guided ankle block.

PMID- 19157372
TI  - Tracheal deviation may be a normal anatomical variant in children.

PMID- 19157373
TI  - Tracheal intubation in a patent with Crouzon's syndrome using LMA-Fastrach with
      the Cook Airway Exchange Catheter.

PMID- 19157375
TI  - [Multiple cystic lesions].

PMID- 19157374
TI  - [A 35-year-old woman with acute abdomen].

PMID- 19157376
TI  - [Recurrent pancreatitis and periampullary cystic tumor].

PMID- 19157377
TI  - [Christian Albert Theodor Billroth].

PMID- 19157378
TI  - Gender difference in the gastric emptying measured by magnetogastrography using a
      semi-solid test meal.
AB  - BACKGROUND/AIMS: evidence of gender-related differences in gastric emptying have
      been reported in the literature. Usually, those researches have focusing only
      with solid or liquid meal and invasive techniques. The objective of this study
      was to know the differences in the half time of gastric emptying and frequency of
      peristaltic contractions measured with magnetogastrography (MGG) on healthy
      subjects, using a semi-solid test meal. METHODS: the study was carried out in 16
      healthy subjects without gastrointestinal disease history they were divided in
      two groups, 8 male and 8 female. A test meal composed by 250 ml of yogurt and 3
      grs of magnetite (Fe3O4), was employed. RESULTS: the gastric emptying half times
      were found to be 32.3 +/- 10.8 and 36.0 +/- 6.7 minutes, for men and women,
      respectively. Magnetogastrography modality presented in this study is a useful
      technique to measure the gastric emptying and the peristaltic contractions
      frequency. The studies were performed in healthy subjects without side effects.
      Using this technique a significant statistical difference (p<0.05) on gastric
      emptying from healthy volunteers was obtained between men and women. CONCLUSIONS:
      a contribution of this study was to demonstrate the feasibility of
      magnetogastrography to analyze gender differences in the gastric emptying half
      time using a semi-solid test meal.

PMID- 19157379
TI  - Cell block technique and cytological smears for the differential diagnosis of
      pancreatic neoplasms after endosonography-guided fine-needle aspiration.
AB  - Cytological smear is widely employed to analyse specimens obtained from
      endosonography-guided fine-needle aspiration (EUS-FNA), but false-negative or
      inconclusive results may occur. A better diagnostic yield can be obtained from
      processing cell blocks. We compared the effectiveness of the cell block technique
      and cytological smear in the diagnosis of pancreatic neoplasms. From January 1997
      to December 2006, 611 patients with pancreatic tumors were evaluated by EUS-FNA.
      Surgery was performed in 356 cases, and the other 255 patients were followed
      clinically for an average of 12.8 months. In total, 282 (46.2%) patients were
      evaluated with cytological smears, and 329 (53.8%) were evaluated using only cell
      blocks. Malignant disease was detected in 352 (57.6%) cases, in which
      adenocarcinoma accounted for 236 (67%) cases. A benign disease was found in the
      other 259 cases, including 35.1% focal chronic pancreatitis and 32.4%
      pseudocysts. Aspiration samples were satisfactory in 595 (97.4%) patients after
      an average of 2.2 (1-4) passes of the needle. Regardless of the cytopathological
      examination technique, EUS-FNA confirmed malignancy in 269 of 352 (76.4%) cases,
      and a benign disease in 257 of 259 (99.2%) cases. For patients who received
      surgery with histologically confirmed lesions, the sensitivity specificity,
      positive and negative predictive values, and accuracy of the smears versus cell
      blocks in diagnosing pancreatic tumors were 61% versus 85.2% (P<0.001), 100%
      versus 93.1%, 100% versus 98.4%, 36% versus 55.1% (P=0.046) and 68% versus 86.5%
      (P<0.001), respectively The cell block technique demonstrated a hig her
      sensitivity, negative predictive value and accuracy than cytological smears.

PMID- 19157380
TI  - [Clinical course of inflammatory bowel disease in patients transplanted for
      primary sclerosing cholangitis].
AB  - Primary sclerosing cholangitis is frequently associated with inflammatory bowel
      disease. OBJECTIVE: to evaluate the evolution of IBD in patients transplanted for
      PSC and the incidence of severe dysplasia/carcinoma. PATIENTS AND METHODS: we
      included 32 patients transplanted between 1988 and 2006 for PSC. Median follow
      up: 8.7 years (1-20 y). All patients were evaluated pre-OLT with colonoscopy and
      multiple intestinal biopsies. Post-OLT surveillance colonoscopies were performed
      every 12 months. RESULTS: of 32 patients included, 26 had inflammatory bowel
      disease pre-OLT (ulcerative colitis 25, Crohn's disease 1). 12 patients had
      active intestinal disease pre-OLT and 2 patients had moderate dysplasia but were
      not surgically treated due to the severity of their liver disease. Among the 26
      patients with IBD pre-OLT, 2 died in the postoperative period due to
      complications related to the transplantation procedure. Among the other 24
      patients, 16 had a quiescent colonic disease post-OLT. Among them, 12 had
      quiescent disease pre-OLT and 4 showed improvement in their colonic symptoms
      after transplantation. Eight patients were symptomatic pre-OLT and had a
      transitory improvement in their symptoms post-OLT, with worsening of their
      intestinal disease by 5.7 +/- 2.8 months after transplantation. Three patients
      developed severe dysplasia or colonic cancer. CONCLUSIONS: over half of patients
      transplanted for PSC presented with quiescent intestinal disease. Yet, there was
      a group of patients that worsened their colonic symptoms and had a high incidence
      of dysplasia/carcinoma. It is necessary to maintain an adequate colonic
      surveillance even in the absence of colonic symptoms or active disease.

PMID- 19157381
TI  - [Cost-effectiveness analysis of entecavir versus lamivudine in patients with
      chronic hepatitis B].
AB  - Chronic hepatitis B infection represent a significant disease burden in Argentina
      and worldwide. New therapeutic strategies are emerging, including entecavir, a
      nucleosid analogue. The objective of the present study was to evaluate the cost
      effectiveness of entecavir vs. lamivudine in Argentina (both in HBeAg positive
      and negative patients). Thus, a decision model that incorporated the main health
      outcomes associated to chronic hepatitis B infection was used, from the main
      Argentina's health system and social perspectives over a ten years time horizon.
      We combined efficacy data from randomized controlled trials, relative risk of
      long-term disease-related complications from observational studies, and life
      tables from Argentine vital statistics. Cost included those of drugs, clinical
      events and their complications. One way sensitivity analyses were performed to
      evaluate uncertainty. Entecavir showed a higher reduction in viral load than
      lamivudine, that implied fewer disease complications such as compensated
      cirrhosis, decompensated cirrhosis and hepatic carcinoma. HBeAg positive and
      negative patients treated with entecavir (discounted results) had 0.49 and 0.57
      years of life gained and 0.44 and 0.51 quality of life adjusted years gained per
      patient in comparison with lamivudine. Results were robust, and showed that the
      most influential parameter was that of entecavir cost. Finally, entecavir showed
      to be from "cost-saving" to "cost-effective" according to the perspective.

PMID- 19157382
TI  - [Toxic hepatitis by consumption Herbalife products a case report].
AB  - Toxic hepatitis by consumption Herbalife products is an affection poorly
      documented and with a great impact in the population due to their massive
      consumption. We present the case of a 63-years-old woman with probable diagnosis
      of toxic hepatitis secondary to the consumption of nutritional supplements
      Herbalife. The nutritional supplements based on natural ingredients are of
      massive consumption worldwide. Because they are recognized like innocuous and of
      non-controlled comercialization, they lack suitable controls. Although there are
      reported cases of hepatotoxicity and other side effects induced by these
      products, there is still not strong evidence to generate a positive reaction of
      the control organisms. We report a case of acute toxic hepatitis potencially due
      to the consumption of Herbalife.

PMID- 19157383
TI  - [Diagnosis and treatment of gastrointestinal bleeding in Bean syndrome].
AB  - Blue Rubber-Bleb Nevus Syndrome (BRBNS, Bean Syndrome) is a rare disorder
      characterized by the presence of cutaneous and visceral vascular malformations.
      Although it may affect several organs, the gastrointestinal tract is one of the
      most frequently involved sites. It can cause gastrointestinal bleeding and
      chronic anemia. We report an 8-years-old girl who was admitted because of
      cutaneous malformations and anemia suspected to be caused by gastrointestinal
      bleeding. Cutaneous lesions were compatible with Blue Rubber-Bleb Nevus Syndrome.
      Vascular malformations were confirmed by diagnostic gastroduodenoscopy and
      colonoscopy and further therapeutical intervention was planned. We performed
      banding of 2 lesions located in the stomach and sclerotherapy of a duodenal
      lesion. Six colonic lesions were treated with banding and three other polypoid
      lesions were endoscopically resected A combined laparoscopic and endoscopic
      approach was performed for evaluation and treatment of small-bowel lesions.
      Eighteen lesions were found. We endoscopically resected 8 polipoid lesions. Eight
      other large transmural lesions were removed by wedge resection. Only one lesion
      required termino-terminal anastomosis. We consider that endoscopic treatment and
      laparoscopically assisted enteroscopy are safe and effective options in the
      treatment of gastrointestinal bleeding caused by vascular malformations.

PMID- 19157384
TI  - Virological and histological re-evaluation of Labrea hepatitis.
AB  - BACKGROUND: a peculiar form of fulminant hepatitis known as Labrea hepatitis,
      probably related to hepatitis B and D, has been reported in Brazilian Amazon as
      early as the 1930s. METHODS: we reviewed the postmortem liver biopsies of 9
      patients with Labrea Hepatitis. Immunostaining for HBV and HDV antigens were
      performed. RESULTS: we found several important characteristics in the liver
      tissues: 1) moderate hepatocellular necro-inflammation, 2) hepatocellular
      ballooning, 3) ballooned hepatocytes with fat droplets surrounding the nucleus
      (morula-like cells or spongiocytes), 4) mild to moderate necrosis and/or mild
      portoseptal fibrosis. Hepatitis B surface antigen (HBsAg) was identified in 7 of
      the 9 cases and was concentrated in the Morula-like cells. Hepatitis B core
      antigen (HBcAg) was present in 5 cases, mostly in the hepatocyte's nucleous. The
      hepatitis D virus antigen (HDV Ag) was present in 5 cases, mostly in the
      cytoplasm and concentrated in the Morula-like cells. CONCLUSION: labrea hepatitis
      is a fatal disease mostly affecting isolated communities in the Amazon. Evidence
      implicates HBV and HDV in the etiology of this disease, but this hypothesis needs
      to be confirmed with genotyping and sequencing research on HBV DNA and HDV RNA
      extracted from the liver and sera of these patients.

PMID- 19157385
TI  - [Therapy of chronic hepatitis B].
AB  - Treatment of Chronic Hepatitis B has changed in the last few years with the
      introduction of oral antivirals (lamivudine, adefovir, entecavir, telbivudine and
      tenofovir) that together with interferon (standard and pegylated) constitute the
      therapeutic arsenal. All of these has permitted to increase the therapy
      indications allowing to treat patients with advance liver disease and
      decompensate liver disease. The main limitation of oral antivirals is the
      emergence of HBV strains drug resistance. The challenge are to prevent the
      emergence of HBV drug resistance and to achieve complete and persistent HBV
      replication in order to avoid the progression of the liver disease and the
      development of HBV related complications.

PMID- 19157386
TI  - [Eosinophilic esophagitis in adults: diagnosis and treatment].

PMID- 19157387
TI  - Aged care will influence nurses' vote.

PMID- 19157388
TI  - Team approach.

PMID- 19157389
TI  - New projects for competency standards.

PMID- 19157390
TI  - Pros and cons of Public Private Partnerships.

PMID- 19157391
TI  - Power to change.

PMID- 19157392
TI  - Rural nurse, city hospital.

PMID- 19157393
TI  - Romantic love and domestic violence.

PMID- 19157394
TI  - Health care changes attitudes in Mali.

PMID- 19157395
TI  - Assisting women's treatment decisions.

PMID- 19157396
TI  - Nurse talk.

PMID- 19157397
TI  - Chief nursing officer makes sense.

PMID- 19157400
TI  - Fair minimum wages: the high road or the low road?

PMID- 19157401
TI  - Consent. Tips for health care professionals.

PMID- 19157402
TI  - Can you hear us? There's a nursing shortage!

PMID- 19157403
TI  - Researching cancer care.

PMID- 19157404
TI  - Ask us! We need a government that is committed to nursing...

PMID- 19157405
TI  - An inspirational poem.

PMID- 19157406
TI  - The price of graduation.

PMID- 19157407
TI  - ICU liaison nurse clinical marker project.

PMID- 19157408
TI  - Frontline nursing detention.

PMID- 19157409
TI  - Nurses can make aged care an election issue.

PMID- 19157411
TI  - Nursing, enterprise bargaining and the Workplace Relations Act.

PMID- 19157412
TI  - The final straw.

PMID- 19157413
TI  - Will nurses in aged care lose out again?

PMID- 19157414
TI  - Organ and tissue transplantation: an Australian perspective.

PMID- 19157415
TI  - Ward nurses aid recovery.

PMID- 19157416
TI  - Patients value friendly nurses.

PMID- 19157417
TI  - Weaning ventilated children safely.

PMID- 19157419
TI  - Get talking!

PMID- 19157418
TI  - Western diseases reach newest nation.

PMID- 19157420
TI  - Brain volumetry counterparts of cognitive impairment in patients with multiple
      sclerosis.
AB  - BACKGROUND: Cognitive impairment is frequent in multiple sclerosis (MS). Tissue
      specific atrophy measures have been shown to correlate with cognitive performance
      in several studies. Voxel-based morphometry (VBM) aims to identify regional
      differences in the local composition of brain tissue and makes possible to
      correlate these findings with cognitive impairment patterns. AIM: To investigate
      the associations between cognitive impairment in MS and tissue-specific atrophy
      and regional distribution of grey matter. METHOD: 15 patients with MS and
      cognitive impairment were included. Demographic (age and years of schooling) and
      clinical (Multiple Sclerosis Functional Composite-MSFC and subtests, Expanded
      Disability Status Scale-EDSS, disease duration) variables were recorded and
      neuropsychological assessments performed (Trail Making Test A and B-TMTA and B,
      Symbol Digit Modalities Test-SDMT, Digit Span Test-DST and Rey's Auditory Verbal
      Learning Test Delayed Recall-RAVLT-DR). Magnetic resonance (MR) 3D sequences
      (MPRAGE) were performed on all subjects and tissue-specific volumes (SIENAx and
      SPM2 software) and VBM grey matter probability maps (SPM2) were obtained.
      RESULTS: Moderate correlations were obtained between tissue volumes obtained with
      SPM2 and SIENAx. Using SIENAx moderate correlations were obtained between
      normalised brain volume (NBV) and disease duration (rho=-0.575, p=0.025) and
      RAVLT-DR (rho=0.518, p=0.048). Using SPM2 moderate correlations were obtained
      between white matter and brain parenchymal fractions (WMF and BPF) and RAVLT-DR
      (rho=0.572 and 0.539, p=0.026 and 0.038), between grey matter fraction (GMF) and
      Z scores on the Paced Auditory Serial Addition Test (PASAT) (rho=0.570, p=0.026),
      and between BPF and disease duration (rho=-0.6, p=0.018). Significant
      correlations were observed only between regional grey matter probability maps and
      grey matter (and to a much lesser extent white matter) volumes from SPM2.
      CONCLUSION: Quantitative tissue-specific atrophy measures may display better
      correlations with patients' variables than regional grey matter atrophy
      distribution obtained using VBM methodology. These results should be confirmed in
      larger samples.

PMID- 19157421
TI  - NNZ-2566: a Gly-Pro-Glu analogue with neuroprotective efficacy in a rat model of
      acute focal stroke.
AB  - The N-terminal cleavage product of human insulin-like growth factor-1 (IGF-1) in
      the brain is the tripeptide molecule Glypromate (Gly-Pro-Glu). Glypromate has
      demonstrated neuroprotective effects in numerous in vitro and in vivo models of
      brain injury and is in clinical trials for the prevention of cognitive impairment
      following cardiac surgery. NNZ-2566 is a structural analogue of Glypromate,
      resulting from alpha-methylation of the proline moiety, which has improved the
      elimination half-life and oral bioavailability over the parent peptide. In vivo,
      NNZ-2566 reduces injury size in rats subjected to focal stroke. An intravenous
      infusion of NNZ-2566 of 4 h duration (3-10 mg/kg/h), initiated 3 h after
      endothelin-induced middle-cerebral artery constriction, significantly reduced
      infarct area as assessed on day 5. Neuroprotective efficacy in the MCAO model was
      also observed following oral administration of the drug (30-60 mg/kg), when
      formulated as a microemulsion. In vitro, NNZ-2566 significantly attenuates
      apoptotic cell death in primary striatal cultures, suggesting attenuation of
      apoptosis is one mechanism of action underlying its neuroprotective effects. NNZ
      2566 is currently in clinical trials for the treatment of cognitive deficits
      following traumatic brain injury, and these data further support the development
      of the drug as a neuroprotective agent for acute brain injury.

PMID- 19157422
TI  - Spinocerebellar ataxia type 6 (SCA6): clinical pilot trial with gabapentin.
AB  - The clinical effect of the GABAergic drug gabapentin was evaluated in 11 patients
      with spinocerebellar ataxia type 6 (SCA6). The total period of gabapentin
      treatment was 4 weeks, and outcome measures were determined with the
      International Cooperative Ataxia Rating Scales (ICARS) and postural sway studies.
      At week 4, 5 patients showed a decrease of the ICARS values by more than 10%
      compared with the pre-treatment baseline. Eight patients showed a more than 10%
      decrease of the sway area (SA) and/or sway path length (SPL) values in postural
      sway studies. The ICARS values and SA/SPL values were not necessarily consistent
      in each patient, but 3 patients showed a more than 10% decrease in the ICRAS, SA,
      and SPL values at week 4 when compared to the pre-treatment baseline. As a whole,
      the efficacy of gabapentin was not statistically confirmed in the 4-week trial
      because of the variation in efficacy in each patient, but the data are indicative
      that some SCA6 patients could benefit from gabapentin treatment.

PMID- 19157423
TI  - A new suture material for hypospadias surgery: a comparative study.
AB  - PURPOSE: We compared the results of hypospadias repair using polyglytone versus
      polydioxanone to evaluate the potential benefit of using a suture with a rapid
      absorption time. MATERIALS AND METHODS: A total of 100 patients 8 to 24 months
      old affected by distal isolated penile hypospadias were considered for this
      study. Patients were randomized and assigned to 2 different groups according to
      the suture material used during the surgical procedure (tubularized incised plate
      repair with or without preputial reconstruction). Polyglytone was used in group A
      and polydioxanone was used in group B. All patients were evaluated at 4 intervals
      (1 week, 1 month, 6 months and 2 years postoperatively). Persistence of sutures
      on penile skin, urethral fistulas, skin dehiscence, infection and skin tracks
      were recorded. Statistical analysis was performed using chi-square test. RESULTS:
      Followup data documented the absence of significant differences in terms of
      urethral fistula rate, skin dehiscence and acute skin infection. Persistence of
      sutures and multiple skin tracks at long-term followup were significantly greater
      in patients in group B. CONCLUSIONS: Both sutures are adequate for hypospadias
      surgery in small children. The use of a rapid absorption monofilament may allow
      much more rapid disappearance of the skin sutures. In the long term this outcome
      means almost complete absence of suture tracks. No statistically significant
      difference in terms of urethrocutaneous fistula was observed, suggesting that the
      tensile strength of polyglytone is adequate.

PMID- 19157425
TI  - Identification of differentially expressed genes in human cryptorchid testes
      using suppression subtractive hybridization.
AB  - PURPOSE: To restore fertility the current consensus suggests early orchiopexy for
      cryptorchidism. However, despite early orchiopexy it is reported that
      transformation of gonocytes into adult dark spermatogonia is already impaired at
      the time of surgery and consequently affects future fertility. To elucidate the
      biological processes occurring during germ cell maturation in the cryptorchid
      testis, we identified the genes affected by testicular maldescent using
      polymerase chain reaction based suppression subtractive hybridization, and
      investigated differentially expressed genes to determine whether they are related
      to cell differentiation and spermatogenesis. MATERIALS AND METHODS: Testicular
      tissues were excised from 24 boys 12 to 59 months old who underwent orchiopexy or
      hydrocelectomy at our hospital. Two-way subtraction was performed to compare
      their tissue samples and those from age matched boys with ipsilateral
      cryptorchidism and a descended testis. Differential expression was validated by
      real-time reverse transcriptase polymerase chain reaction. To clarify the
      distribution of candidate genes, immunohistochemical and western blot analysis
      was performed. RESULTS: We obtained 84 clones corresponding to transcripts
      representing differential expression. Basic local alignment search tool searches
      revealed 32 different known genes with 98% to 100% similarity. Among these genes
      we further investigated 3 genes, TPT1, EEF1A1 and NuMA1, which were significantly
      more highly expressed in cryptorchidism than in descended testes and were
      detected in the spermatogonia from immature to adult testes. CONCLUSIONS: TPT1,
      EEF1A1 and NuMA1 have cell growth related functions, suggesting that they have
      certain roles in germ cell differentiation and maintenance of stem cell
      potential. Changes in the expression levels of these genes in the testes might
      enable novel evaluation of spermatogenic failure caused by cryptorchidism.

PMID- 19157427
TI  - Appearance of dextranomer/hyaluronic Acid copolymer implants on computerized
      tomography after endoscopic treatment of vesicoureteral reflux in children.
AB  - PURPOSE: With the increasing popularity of endoscopic treatment for
      vesicoureteral reflux in children, dextranomer/hyaluronic acid copolymer implants
      are more frequently detected on computerized tomography, which may lead to
      misinterpretation and unnecessary intervention. The objective of this study was
      to characterize the long-term appearance of dextranomer/hyaluronic acid copolymer
      implants on computerized tomography. MATERIALS AND METHODS: We evaluated the
      hospital charts of 893 patients who had undergone dextranomer/hyaluronic acid
      copolymer injection for vesicoureteral reflux between July 2001 and November 2007
      to identify those who underwent subsequent computerized tomography of the abdomen
      and pelvis. A total of 30 patients with ureterovesical junction stones served as
      the control group. Seven patients who proceeded to extravesical reimplantation
      after failed endoscopic treatment had dextranomer/hyaluronic acid copolymer
      implants explanted and microscopically evaluated. RESULTS: Of 893 patients who
      had undergone endoscopic treatment for vesicoureteral reflux 17 (1.9%) underwent
      subsequent computerized tomography. A total of 33 dextranomer/hyaluronic acid
      copolymer implants were detected on computerized tomography, and were classified
      as low density (21) or high density (12). Median density was 22 HU (range 15 to
      27) for low density implants and 193 HU (126 to 367) for high density implants.
      Radiograph of the kidneys, ureters and bladder, and fluoroscopy did not visualize
      high density implants. Neither gender, age at endoscopic treatment,
      vesicoureteral reflux grade, hydrodistention grade, injection volume, success nor
      second injection was associated with a high density implant. Only elapsed time
      between surgery and computerized tomography was associated with increased implant
      density (p = 0.02). CONCLUSIONS: Dextranomer/hyaluronic acid copolymer implants
      may be encountered on computerized tomography as low or high density lesions.
      History of vesicoureteral reflux and absence of hydronephrosis as well as
      hematuria should provide reassurance and prevent inappropriate intervention for
      misdiagnosed ureteral stones.

PMID- 19157429
TI  - Re: It's time to abandon an upper limit of normal for prostate specific antigen:
      assessing the risk of prostate cancer: I. M. Thompson, D. P. Ankerst, R. Etzioni
      and T. Wang J Urol 2008; 180: 1219-1222.

PMID- 19157430
TI  - Comparison of semi-empirical and computer derived methods for estimating urinary
      saturation of brushite.
AB  - PURPOSE: The Equil 2 computer program has been questioned by the new Joint Expert
      Speciation System program (Mayhem Unit Trust and Council for Scientific and
      Industrial Research, Pretoria, South Africa) for estimating the urinary
      saturation of stone forming salts to gauge the propensity for stone formation. To
      attempt resolution the supersaturation index according to the Joint Expert
      Speciation System and the relative saturation ratio according to Equil 2 were
      compared with the semi-empirically derived concentration-to-product ratio.
      MATERIALS AND METHODS: Data were obtained from a recent article in The Journal of
      Urology(R), in which pH, calcium and citrate were varied over a wide range in 72
      urine samples. We calculated the relative saturation ratio and the
      supersaturation index of brushite, and compared them with the available
      concentration-to-product ratio derived from the growth or dissolution of
      synthetic brushite. RESULTS: The mean concentration-to-product ratio did not
      differ from the supersaturation index but the concentration-to-product ratio and
      the supersaturation index were significantly lower than the relative saturation
      ratio (p <0.004). On the saturation value and urinary variable plot the relative
      saturation ratio could be readily distinguished from the concentration-to-product
      ratio because it was consistently and significantly higher. While the
      supersaturation index pattern was similar to the concentration-to-product ratio,
      the supersaturation index was slightly lower at high urinary pH and calcium, and
      slightly higher at lower urinary pH and calcium (p <0.001). When the
      Ca(2)H(2)(PO(4))(2) complex was deleted from the Joint Expert Speciation System,
      the corrected supersaturation index was not significantly different from the
      relative saturation ratio determined by Equil 2. CONCLUSIONS: The relative
      saturation ratio overestimates brushite saturation by about 80%. The
      supersaturation index yields a good approximation of brushite saturation at
      modest degrees of saturation but it overestimates saturation at low pH or calcium
      (low saturation) and underestimates it at high pH or calcium (high saturation).

PMID- 19157431
TI  - Spontaneous contractions evoke afferent nerve firing in mouse bladders with
      detrusor overactivity.
AB  - PURPOSE: Afferent nerve firing has been linked to spontaneous bladder
      contractions in a number of lower urinary tract pathologies and it may lead to
      urgency and incontinence. Using optical mapping, single unit recording and
      tension measurements we investigated the correlation between afferent nerve
      firing and spontaneous bladder contractions in spinal cord transected mice.
      MATERIALS AND METHODS: Bladder-nerve preparations (bladder sheets and the
      associated L6-S2 pelvic nerves) were dissected from normal and spinal cord
      transected mice showing overactivity on cystometry and opened along the ventral
      aspect from base to dome. Bladder sheets were mounted horizontally in a
      temperature regulated chamber to simultaneously record Ca(2+) transients across
      the mucosal surface, single unit afferent nerve firing and whole bladder tension.
      RESULTS: Single unit afferent fibers were identified by probing their receptive
      fields. Fibers showed a graded response to von Frey stimulation and a frequency
      of afferent firing that increased as a function of the degree of stretch. Optical
      maps of Ca(2+) transients in control bladders demonstrated multiple initiation
      sites that resulted in high frequency, low amplitude spontaneous contractions.
      Alternatively in maps of the bladders of spinal cord transected mice Ca(2+)
      transients arose from 1 or 2 focal sites, resulting in low frequency, high
      amplitude contractions and concomitant afferent firing. CONCLUSIONS: Large
      amplitude, spontaneous bladder contractions evoke afferent nerve activity, which
      may contribute to incontinence.

PMID- 19157432
TI  - Receptor isoforms that mediate estrogen and progestagen action in the female
      lower urinary tract.
AB  - PURPOSE: Bladder symptoms can be ameliorated by sex steroids but to our knowledge
      the mechanism of action is unknown. Previous studies of steroid receptor
      expression in the bladder did not indicate receptor subtype expression. We report
      the distribution of estrogen and progesterone receptor isoforms in the female
      lower urinary tract. MATERIALS AND METHODS: Prospectively recruited women
      undergoing routine urogynecological or gynecological surgery provided cold cup
      biopsy samples from the bladder dome, trigone, and proximal and distal urethra.
      The samples were immediately frozen or fixed in formalin. After RNA extraction
      transcripts for estrogen receptor alpha and beta, and progesterone receptor A and
      B were noted on reverse transcriptase-polymerase chain reaction using isoform
      specific primers. The precise cellular localization of receptor proteins and
      their relative levels were assessed by immunochemistry in formalin fixed tissue
      sections with isoform specific antibodies. RESULTS: Nine premenopausal and 10
      postmenopausal women were recruited into the study. Two postmenopausal women on
      hormone replacement therapy. Estrogen receptor alpha and beta, and progesterone
      receptor A and B transcripts were detected in whole bladder extracts. Nuclear
      estrogen receptor alpha immunoreactivity was present in squamous epithelium but
      absent from transitional epithelium. Estrogen receptor beta immunoreactivity was
      expressed in squamous and transitional cell epithelium. Nuclear progesterone
      receptor expression was present in urethral squamous epithelium only.
      Progesterone receptor expression was greater in premenopausal women and in
      postmenopausal women on estrogen. CONCLUSIONS: Estrogen receptor alpha and beta
      genes are transcribed in bladder tissue but only estrogen receptor beta is
      translated into protein, suggesting that the urothelium responds to endogenous
      estrogen via estrogen receptor beta. Progesterone receptor expression is confined
      to urethral squamous epithelium and the major isoform is progesterone receptor A.

PMID- 19157433
TI  - Increased urokinase-type plasminogen activator receptor and epidermal growth
      factor receptor in serum of patients with prostate cancer.
AB  - PURPOSE: Prostate cancer cell motility and invasion have been linked to the up
      regulated signaling of epidermal growth factor receptor and urokinase-type
      plasminogen activator receptor. We analyzed the expression of serum urokinase
      type plasminogen activator receptor and epidermal growth factor receptor in the
      serum of patients with clinical suspicion of prostate cancer to evaluate the
      possible role as prostate cancer markers. MATERIALS AND METHODS: Serum was
      collected from 79 consecutive patients referred to our institution for
      transrectal ultrasound guided prostate biopsy. All blood samples were obtained
      before prostate biopsy. Total urokinase-type plasminogen activator receptor and
      epidermal growth factor receptor antigen in serum were measured by specific
      enzyme-linked immunosorbent assays. Gleason score, the number of positive cores,
      maximum percent of cancer and inflammation were considered on biopsy. Patients
      determined to have prostate adenocarcinoma underwent radical retropubic
      prostatectomy. Gleason score, pathological stage (extraprostatic extension),
      surgical margins, seminal vesicle involvement, perineural infiltration,
      lymphovascular invasion and cancer volume were evaluated in radical retropubic
      prostatectomy specimens. RESULTS: The 30 patients with prostate cancer had
      significantly higher levels of serum urokinase-type plasminogen activator
      receptor and epidermal growth factor receptor in comparison to those without
      prostate cancer but not significantly higher levels of prostate specific antigen.
      Urokinase-type plasminogen activator receptor and epidermal growth factor
      receptor levels closely correlated in the serum of patients with prostate cancer.
      In a multivariate model high serum epidermal growth factor receptor increased the
      probability of positive biopsies by 1.9 times. ROC analysis revealed that serum
      epidermal growth factor receptor had 93.3% sensitivity and 98% specificity for
      detecting prostate cancer at a cutoff of 67.9 ng/ml. Urokinase-type plasminogen
      activator receptor and epidermal growth factor receptor were significantly higher
      in patients with extraprostatic extension, seminal vesicle involvement and
      perineural infiltration in the radical retropubic prostatectomy specimens. Serum
      urokinase-type plasminogen activator receptor was the only independent predictive
      serum marker of extraprostatic extension, seminal vesicle involvement and
      perineural infiltration. CONCLUSIONS: The measurement of urokinase-type
      plasminogen activator receptor and epidermal growth factor receptor in the serum
      of patients with clinical suspicion of prostate cancer might provide clinically
      relevant information on the state of the prostate gland. Measuring serum
      epidermal growth factor receptor could help predict which patients have prostate
      cancer, while serum urokinase-type plasminogen activator receptor over expression
      seems to be related to tumor extraprostatic spread.

PMID- 19157434
TI  - Re: Assessment of early continence after reconstruction of the periprostatic
      tissues in patients undergoing computer assisted (robotic) prostatectomy: results
      of a 2 group parallel randomized controlled trial: M. Menon, F. Muhletaler, M.
      Campos and J. O. Peabody J Urol 2008; 180: 1018-1023.

PMID- 19157435
TI  - Re: Management of ureteral obstruction due to advanced malignancy: optimizing
      therapeutic and palliative outcomes: E. Kouba, E. M. Wallen and R. S. Pruthi J
      Urol 2008; 180: 444-450.

PMID- 19157436
TI  - Re: Daily cranberry juice for the prevention of asymptomatic bacteriuria in
      pregnancy: a randomized, controlled pilot study: D. A. Wing, P. J. Rumney, C. W.
      Preslicka and J. H. Chung J Urol 2008; 180: 1367-1372.

PMID- 19157438
TI  - Re: Lichen sclerosus: review of the literature and current recommendations for
      management: J. M. Pugliese, A. F. Morey and A. C. Peterson J Urol 2007; 178: 2268
      2276.

PMID- 19157439
TI  - Re: The pediatric penile perception score: an instrument for patient self
      assessment and surgeon evaluation after hypospadias repair: D. M. Weber, V. B.
      Schonbucher, M. A. Landolt and R. Gobet J Urol 2008; 180: 1080-1084.

PMID- 19157440
TI  - Phosphorylated H2AX in noninvasive low grade urothelial carcinoma of the bladder:
      correlation with tumor recurrence.
AB  - PURPOSE: Histone modifications have been linked to DNA replication, transcription
      and repair. The phosphorylation of histone H2AX at serine 139 (gamma-H2AX) is
      associated with DNA breaks. gamma-H2AX has been shown to be expressed in bladder
      urothelial carcinoma. To our knowledge studies of the relationship of gamma-H2AX
      expression and the clinical outcome of urothelial carcinoma are lacking. Hence,
      we evaluated the rate of H2AX phosphorylation in low grade bladder urothelial
      carcinoma and assessed its potential role for predicting recurrence and/or
      progression. MATERIALS AND METHODS: Immunohistochemical expression of gamma-H2AX
      using a polyclonal antibody was retrospectively assessed in 2 groups of patients
      from The Johns Hopkins Hospital with low grade bladder urothelial carcinoma.
      Group 1 consisted of transurethral resection biopsies from 18 patients from 2004
      to 2006 that were retrieved from our surgical pathology files. Group 2 consisted
      of 42 archival transurethral biopsies obtained between 1971 and 1995 with longer
      followup that were used to construct a tissue microarray. RESULTS: On univariate
      analysis recurrence in the entire cohort was more likely to develop in gamma-H2AX
      negative than in gamma-H2AX positive cases (24 of 32 or 81% vs 13 of 28 or 46%).
      The difference in recurrence was statistically significant (p = 0.02). The same
      was true in group 2 (16 of 21 cases or 76% vs 9 of 21 or 43%, p = 0.02). Female
      gender and intravesical therapy were also associated with a higher recurrence
      rate in our cohort. A higher progression rate was noted in group 2 patients and
      in the entire cohort in association with negative gamma-H2AX staining. However,
      the difference in progression between gamma-H2AX negative and positive tumors was
      not statistically significant. On multivariate analysis only patient gender and
      prior intravesical treatment remained predictive of recurrence (p <0.03).
      CONCLUSIONS: Our data suggest that epigenetic alterations may have an important
      role in the mechanism of bladder tumor recurrence. Analysis in a larger cohort is
      needed to further assess our current preliminary findings of the role of gamma
      H2AX expression for predicting outcome in low grade urothelial carcinoma cases.

PMID- 19157442
TI  - The fate of the seminal vesicle remnant after proximal transection or ligation:
      an animal model.
AB  - PURPOSE: Dissection of the seminal vesicles during radical prostatectomy has the
      potential to damage the pelvic plexus, thus compromising trigonal, bladder neck
      and cavernous innervation, and contributing to delayed gain of continence and
      erectile function. The rate of prostate cancer invasion into the seminal vesicles
      in currently operated patients is low and in most it may be predicted
      preoperatively. This situation calls for seminal vesicle sparing radical
      prostatectomy in select patients, leaving a distal remnant of the seminal
      vesicles in place. We investigated the fate of the seminal vesicle remnant after
      proximal transection or ligation in an animal model. MATERIALS AND METHODS: The
      right seminal vesicle in 36 anesthetized male rats was divided by suture ligation
      or by transection. The left seminal vesicle served as a control. Six rats per
      group were sacrificed 1, 2 and 4 weeks after division, respectively. Seminal
      vesicle morphology was evaluated macroscopically and microscopically. RESULTS:
      All rats tolerated surgery well and gained weight postoperatively. Transected
      seminal vesicles were similar in weight and morphology to control contralateral
      glands. One week after seminal vesicle ligation the remnants became significantly
      heavier and showed balloon dilatation of the hollow spaces, while the lining
      epithelium became significantly flattened. Two and 4 weeks after ligation half of
      the animals showed gland shrinkage and half demonstrated persistent dilatation.
      CONCLUSIONS: Seminal vesicle transection preserves the gland remnant in a
      relatively normal morphology, while ligation leads to severe and inconsistent
      morphological changes. When considering seminal vesicle sparing radical
      prostatectomy, seminal vesicle transection may be preferred to ligation.

PMID- 19157444
TI  - Urodynamic measurements by radiotelemetry in conscious, freely moving beagle
      dogs.
AB  - PURPOSE: Urodynamics have been traditionally recorded in anesthetized or
      conscious animals implanted with a bladder catheter that is used to artificially
      fill the bladder while measuring intravesicular bladder pressure. Anesthesia
      alters the urodynamics and in the conscious state this methodology requires that
      the dogs be tethered/restrained, which evokes stress and limits the period of
      continuous urodynamic assessment. A more physiological and chronic method of
      evaluating pharmacological responses on urodynamics is necessary. MATERIALS AND
      METHODS: Adult female beagle dogs were surgically instrumented with
      radiotelemetry transmitters enabling urodynamic/hemodynamic recordings.
      Telemetered urodynamics were compared to those measured in anesthetized dogs
      receiving bladder infusion of saline. The response to diuresis with furosemide
      (Intervet, Millsboro, Delaware) and the M3 selective antimuscarinic darifenacin
      (Matrix Laboratories, Hyderabad, India) were evaluated. RESULTS: Saline infused,
      anesthetized dogs demonstrated lower peak micturition pressure and higher
      threshold pressure than conscious, freely moving telemetered dogs. In telemetered
      dogs a single dose of furosemide increased voiding frequency and average urine
      volume per void. Darifenacin decreased peak voiding pressure without affecting
      voiding frequency. CONCLUSION: Telemetry provides the potential to significantly
      decrease animal use while enabling the continuous monitoring of urodynamics under
      more physiological conditions without tethering or artificial filling. In
      addition, this new model facilitates evaluation of the chronic efficacy of new
      urological therapies.

PMID- 19157443
TI  - S1P/S1P2 signaling induces cyclooxygenase-2 expression in Wilms tumor.
AB  - PURPOSE: Cyclooxygenase-2 has been reported to be ubiquitously expressed in Wilms
      tumor, the most common malignant renal tumor in children. However, to our
      knowledge the regulation mechanism of cyclooxygenase-2 expression remains
      unexplored. MATERIALS AND METHODS: Quantitative real-time polymerase chain
      reaction and Western blot were performed to detect cyclooxygenase-2 mRNA and
      protein expression in WiT49 cells upon stimulation by S1P (Biomol(R)), and S1P(2)
      and cyclooxygenase-2 mRNA expression in 10 freshly frozen Wilms tumor tissues and
      matched normal tissues. Over expression, blockade and down-regulation of S1P(2)
      were determined using adenoviral transduction, the S1P(2) antagonist JTE-013
      (Tocris Bioscience, Ellisville, Missouri) and small interfering RNA (Dharmacon,
      Lafayette, Colorado) transfection, respectively. The prostaglandin E(2) level in
      WiT49 cells was determined by gas chromatography/mass spectrometry. RESULTS: S1P
      induced cyclooxygenase-2 mRNA and protein expression in WiT49 cells in a
      concentration dependent manner. Over expression of S1P(2) in WiT49 cells led to a
      significant increase in cyclooxygenase-2 mRNA and protein expression as well as
      subsequent prostaglandin E(2) synthesis. In addition, pretreatment of those cells
      that over expressed S1P(2) with the S1P(2) selective antagonist JTE-013
      completely blocked S1P induced cyclooxygenase-2 protein expression. In accordance
      with these results silencing S1P(2) in WiT49 cells down-regulated S1P induced
      cyclooxygenase-2 expression. Further research in 10 Wilms tumor specimens showed
      that S1P(2) mRNA is greatly increased in Wilms tumor. CONCLUSIONS: S1P induced
      cyclooxygenase-2 expression in Wilms tumor and this effect was mediated by
      S1P(2). This finding extends the biological function of S1P(2) and provides the
      biochemical basis for developing inhibitors targeting the S1P/cyclooxygenase-2
      signaling pathway.

PMID- 19157445
TI  - Role of alpha2-adrenoceptors and glutamate mechanisms in the external urethral
      sphincter continence reflex in rats.
AB  - PURPOSE: We investigated the role of alpha(2)-adrenoceptors and glutamate
      mechanisms in the urethral continence reflex in response to abdominal pressure
      increases. MATERIALS AND METHODS: Under urethane anesthesia external urethral
      sphincter electromyogram activity was evaluated in spinal cord transected (T8-T9)
      female rats during lower abdominal wall compression before and after intravenous
      application of test drugs. The effects of the N-methyl-D-aspartate glutamate
      receptor antagonist MK-801 (Sigma) or the alpha(2)-adrenoceptor agonist
      medetomidine (Tocris Cookson, Ellisville, Missouri) (each 0.03, 0.3 and 3 mg/kg
      intravenously) on external urethral sphincter activity were examined. A 0.3 mg/kg
      intravenous dose of the alpha(2)-adrenoceptor antagonist idazoxan (Sigma) was
      then administered before or after the application of 1 mg/kg MK-801
      intravenously. In addition, 0.3 mg/kg idazoxan were administered intravenously
      following the application of 1 mg/kg of the serotonin/norepinephrine reuptake
      inhibitor duloxetine (Kemprotec, Middlesbrough, United Kingdom) intravenously.
      RESULTS: MK-801 and medetomidine dose dependently decreased external urethral
      sphincter activity. Idazoxan significantly increased external urethral sphincter
      activity by 64% but the increase in activity after idazoxan was abolished by MK
      801. On the other hand, idazoxan did not reverse the inhibitory effects of MK
      801. In addition, idazoxan significantly potentiated the duloxetine effects on
      external urethral sphincter activity by 120%. CONCLUSIONS: These results indicate
      that 1) glutamate is a major excitatory neurotransmitter in the urethral
      continence reflex response to abdominal pressure increases, 2) alpha(2)
      adrenoceptor activation suppresses external urethral sphincter activity, probably
      via presynaptic inhibition of glutamate release and 3) the effects of
      serotonin/norepinephrine reuptake inhibitors are enhanced by alpha(2)
      adrenoceptor inhibition. Therefore, alpha(2)-adrenoceptor antagonists could be
      beneficial for treating stress urinary incontinence.

PMID- 19157446
TI  - Response of bladder carcinoma cells to TRAIL and antisense oligonucleotide, Bcl-2
      or clusterin treatments.
AB  - PURPOSE: Bladder transitional cell carcinoma is the second most common urological
      malignancy, of which 80% are superficial disease limited to the bladder.
      Superficial bladder transitional cell carcinoma has a high propensity for
      recurrence and progression after initial resection, necessitating adjuvant
      intravesical therapy. TRAIL (tumor necrosis factor-related apoptosis inducing
      ligand) can selectively induce apoptosis in most tumor cells while sparing normal
      cells. TRAIL drives not only the death receptor pathway, but also the
      mitochondrial pathway through Bid. Due to the anti-apoptotic functions of Bcl-2
      and clusterin on the mitochondrial apoptotic pathway the effects of down
      regulating these proteins were examined in partially TRAIL resistant bladder
      transitional cell carcinoma cell lines. MATERIALS AND METHODS: Antisense
      oligonucleotides targeting Bcl-2 and clusterin were used alone or combined with
      TRAIL and cytotoxicity was examined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolim bromide) proliferation assay. Apoptotic pathway signals were
      detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western
      blotting after the various combination treatments. All statistical tests were 2
      sided. RESULTS: Although no direct correlation between TRAIL sensitivity and the
      relative expression levels of Bcl-2 and clusterin was found in the bladder
      transitional cell carcinoma cell lines examined, antisense oligonucleotide
      mediated the down-regulation of Bcl-2 and clusterin, increasing the sensitivity
      of the partially resistant cells to TRAIL. This was mediated through increased
      apoptotic signaling of the mitochondrial pathway, as evident by the increased
      activation of caspase-9 and 3, and cleaved DFF45. There was no benefit of
      combined antisense oligonucleotide therapy. CONCLUSIONS: This study provides
      proof of principle that TRAIL combined with antisense oligonucleotide-Bcl-2 may
      have potential as a novel future treatment strategy for bladder transitional cell
      carcinoma.

PMID- 19157447
TI  - Mucosal muscarinic receptors enhance bladder activity in cats with feline
      interstitial cystitis.
AB  - PURPOSE: Interstitial cystitis is a chronic pelvic pain syndrome of which the
      origin and mechanisms involved remain unclear. In this study Ca(2+) transients in
      the bladder wall of domestic cats diagnosed with naturally occurring feline
      interstitial cystitis were examined. MATERIALS AND METHODS: Cross-sections of
      full-thickness bladder strips from normal cats and cats with feline interstitial
      cystitis were examined by optically mapping Ca(2+) transients and recording
      tension. Responses of Ca(2+) activity and detrusor contractions to
      pharmacological interventions were compared. In addition, pharmacological
      responses were compared in mucosa denuded preparations. RESULTS: Optical mapping
      showed that feline interstitial cystitis bladders had significantly more
      spontaneous Ca(2+) transients in the mucosal layer than control bladders. Optical
      mapping also demonstrated that feline interstitial cystitis bladders were
      hypersensitive to a low dose (50 nM) of the muscarinic receptor agonist
      arecaidine when the mucosal layer was intact. This hypersensitivity was markedly
      decreased in mucosa denuded bladder strips. CONCLUSIONS: In feline interstitial
      cystitis cat bladders there is increased Ca(2+) activity and sensitivity of
      muscarinic receptors in the mucosal layer, which can enhance smooth muscle
      spontaneous contractions.

PMID- 19157448
TI  - Predicting prostate cancer biochemical recurrence using a panel of serum
      proteomic biomarkers.
AB  - PURPOSE: The pathological state of the prostate may be reflected by serum
      proteome in a man. We hypothesized that biomarkers are present in preoperative
      serum, which may be used to predict the probability of biochemical recurrence
      following radical prostatectomy. MATERIALS AND METHODS: Mass spectrometry
      analysis was used to compare 52 men who experienced biochemical recurrence with
      52 who remained biochemical recurrence-free for approximately 5 years after
      radical retropubic prostatectomy. A total of 30 matched pairs of recurrent and
      nonrecurrent serum samples were randomly selected as a training set for biomarker
      discovery and model development. Selected mass spectrometry peaks were combined
      with pre-radical retropubic prostatectomy prostate specific antigen in a
      multivariate algorithm to predict recurrence. The algorithm was evaluated using
      the remaining 22 recurrent and 22 nonrecurrent subjects as test samples. Protein
      identities of the selected mass spectrometry peaks were investigated. RESULTS:
      Two serum biomarkers for recurrence, P1 and P2, were combined with preoperative
      prostate specific antigen to predict biochemical recurrence. The ROC AUC for
      prostate specific antigen and the predicted outcome was 0.606 and 0.691 in the
      testing data, respectively. Using a single cutoff the samples were divided into 2
      groups that were predictive of biochemical recurrence (p = 0.026). In contrast,
      preoperative prostate specific antigen did not differ between recurrent and
      nonrecurrent cases (Wilcoxon matched pairs test p = 0.07). The protein identity
      of P1 was determined to be a truncated form of C4a (C4a des-Arg). Preliminary
      data indicated that P2 was an N-terminal fragment of protein C inhibitor.
      CONCLUSIONS: In the current study population, which was matched on Gleason score
      and TNM staging, pre-radical retropubic prostatectomy prostate specific antigen
      retained no independent power to predict recurrence. However, by adding 2
      proteomic biomarkers to preoperative prostate specific antigen the combined model
      demonstrated statistically significant value for predicting prostate cancer
      recurrence in men who underwent radical retropubic prostatectomy.

PMID- 19157449
TI  - Effect of 1,25-dihydroxyvitamin d on testicular morphology and gene expression in
      experimental cryptorchid mouse: testis specific cDNA microarray analysis and
      potential implication in male infertility.
AB  - PURPOSE: We evaluated the morphological effect and alterations in gene expression
      caused by 1,25-dihydroxyvitamin D treatment in the mouse testis undergoing
      experimental cryptorchidism and subsequent orchiopexy. MATERIALS AND METHODS: The
      mean modified Johnsen score and testicular weight were estimated after 4 weeks of
      treatment with a 1,25-dihydroxyvitamin D prodrug. We examined sites of vitamin D
      receptor and mRNA expression, and 1,25-dihydroxyvitamin D analogue accumulation
      in the mouse testis. Also, we compared alterations in gene expression in the
      cryptorchid mouse testis with or without 1,25-dihydroxyvitamin D administration
      by testis specific cDNA microarray. We confirmed protein synthesis of a candidate
      among up-regulated genes in primary cultures of Sertoli's cells by Western
      blotting. RESULTS: Mean +/- SEM Johnsen score and testicular weight were
      increased by 1,25-dihydroxyvitamin D treatment but not significantly (6.12 +/-
      0.33 vs 5.27 +/- 0.4 and 49.3 +/- 3.8 mg vs 42.6 +/- 5.5, p = 0.13 and 0.065,
      respectively). Vitamin D receptor and its mRNA were positive in Sertoli's cells.
      The 1,25-dihydroxyvitamin D analogue accumulated mainly in Sertoli's cells. Of
      2,483 testis specific genes 19 showed up-regulation by 1,25-dihydroxyvitamin D
      treatment. Of these genes the regulator of cellular cholesterol homeostasis Abca1
      was expressed mainly in Sertoli's cells and influenced male fertility. In primary
      cultures of Sertoli's cells the synthesis of Abca1 protein was increased by 1,25
      dihydroxyvitamin D treatment but not by follicle-stimulating hormone or
      testosterone treatment. CONCLUSIONS: We noted that 1,25-dihydroxyvitamin D
      contributes to spermatogenesis by up-regulating certain specific genes in
      Sertoli's cells. Testis specific cDNA microarray analysis and vitamin D
      supplementation may have implications for managing male infertility.

PMID- 19157450
TI  - Temporal coordination of pelvic and perineal striated muscle activity during
      micturition in female rabbits.
AB  - PURPOSE: To determine the motor basis of urine expulsion the activity of the
      pelvic (pubococcygeus) and perineal (bulbospongiosus and ischiocavernosus)
      muscles was recorded during micturition in anesthetized female rabbits. MATERIAL
      AND METHODS: Virgin female chinchilla rabbits were used for simultaneously
      recording cystometrograms and electromyograms of the pubococcygeus,
      ischiocavernosus and bulbospongiosus muscles. The particular contribution of each
      muscle during micturition was analyzed in another set of experiments in which
      each was inactivated by bilateral lidocaine injection. Bladder function was
      assessed using standard urodynamic parameters. RESULTS: Cystometrography showed
      that micturition comprises 2 phases, that is storage and voiding phases. During
      the latter phase no high frequency oscillations were recorded. On simultaneous
      electromyography recordings a temporal, coordinated activation of pelvic
      (pubococcygeus) and perineal (bulbospongiosus and ischiocavernosus) muscles was
      observed. During specific blockade of each muscle some modifications in
      urodynamic parameters were found. CONCLUSIONS: Our findings indicate a specific
      role for the pelvic and perineal muscles during feminine micturition.

PMID- 19157452
TI  - Re: Evaluation of current TNM classification of penile carcinoma: J. A. Leijte,
      M. Gallee, N. Antonini and S. Horenblas J Urol 2008; 180: 933-938.

PMID- 19157453
TI  - Re: Stress urinary incontinence: relative importance of urethral support and
      urethral closure pressure; J. O. DeLancey, E. R. Trowbridge, J. M. Miller, D. M.
      Morgan, K. Guire, D. E. Fenner, W. J. Weadock and J. A. Ashton-Miller J Urol
      2008; 179: 2286-2290.

PMID- 19157454
TI  - Preventing bladder tumor implantation with photodynamic therapy in a rat model
      mimicking post-fluorescence guided transurethral resection.
AB  - PURPOSE: Fluorescence guided transurethral resection has gained acknowledgment
      from the urological community and it is progressively becoming more applied. It
      has been shown to decrease the recurrence rate of nonmuscle invasive bladder
      cancer due to incomplete resection due to lack of visualization. The implantation
      of viable tumor cells seeded during transurethral resection is another reason for
      recurrence. We investigated whether applying photodynamic therapy on sensitized
      tumor cells would decrease the amount of viable intraluminal cells and tumor cell
      implantation. MATERIAL AND METHODS: Two models were designed to mimic the
      situation after fluorescence guided transurethral resection, including partly or
      fully de-epithelialized bladders and circulating tumor cells loaded with
      protoporphyrin IX. Photodynamic therapy was performed. Controls consisted of no
      drug with no light, light only and drug only. Immediately after photodynamic
      therapy the intravesical contents were retrieved and clonogenic assays were
      performed on cells. Bladders were harvested 10 days after cell administration and
      subjected to pathological analysis. RESULTS: In the photodynamic therapy and
      control groups tumor volume was proportional to the instilled cell load.
      Clonogenic assays showed that viable cells were decreased a tenth of the initial
      administered amount. Tumor implantation decreased to less than a fifth of control
      values. CONCLUSIONS: Photodynamic therapy can effectively decrease the amount of
      viable tumor cells in the bladder lumen. This results in a significant decrease
      in tumor implantation. This technique could possibly be used to further decrease
      the recurrence rate of nonmuscle invasive bladder cancer.

PMID- 19157456
TI  - Maximizing stone fragmentation efficiency with ultrasonic probes: impact of probe
      pressure and rotation.
AB  - PURPOSE: We examined the effects of probe rotation and pressure on stone
      fragmentation in an in vitro percutaneous nephrolithotomy model. MATERIALS AND
      METHODS: The study was a fully randomized, factorial experiment with 20 repeat
      trials performed at each combination of variables, yielding a total of 300 trials
      per device for ultrasonic tests and 360 for ultrasonic/pneumatic combination
      tests. Varying masses were placed on the hand piece of each device to create a
      probe contact pressure of 400, 1,000 or 2,000 gm. The impact of rotation was
      tested only at 0 or 90 degrees and rotating only at a frequency of 2 Hz.
      Statistical analysis was performed using R, version 2.6.2. RESULTS: For the
      Cyberwand the Tukey HSD test showed that 400 and 1,000 gm probe pressure were
      significantly more effective than 2,000 gm pressure (p <0.05). The range and
      frequency of rotation were not statistically significant variables affecting
      Cyberwand efficiency. For the LithoClast Ultra using only the ultrasonic probe
      significant differences were found among the 3 pressure levels (400, 1,000 and
      2,000 gm, respectively, p <0.05). For rotation 90 degrees were significantly more
      effective than 0 degrees (p <0.05) at a mean +/- SD stone mass of 0.168 +/- 0.078
      and 0.107 +/- 0.09 gm, respectively. For the LithoClast Ultra
      ultrasonic/pneumatic combination 1,000 gm pressure were significantly more
      effective than 400 or 2,000 gm (p <0.05). The 6 and 12 Hz pneumatic frequencies
      outperformed 3 Hz but were not significantly different from each other (p <0.05).
      CONCLUSIONS: Differences in probe manipulation impact stone fragmentation
      efficiency and procedural success.

PMID- 19157457
TI  - Primary Ewing sarcoma/primitive neuroectodermal tumor of the kidney.

PMID- 19157458
TI  - A novel device for protecting rectum during prostate cancer irradiation: in vivo
      data on a large mammal model.
AB  - PURPOSE: Hypofractionation schemes and associated higher rectal doses have evoked
      the need for improved protection of the rectum during prostate cancer
      irradiation. MATERIALS AND METHODS: An implantable, biodegradable, inflatable,
      preshaped triangular balloon of commercially used poly(L-lactide-co-epsilon
      caprolactone) co-polymer material was developed to provide separation between
      prostate and rectum. Biocompatibility and degradability of the balloon implanted
      subcutaneously or perineally, and in the context of transperineal implantation
      and local irradiation were evaluated in several in vivo studies. RESULTS: The
      device was found to be biocompatible in subcutaneously implanted rabbits up to 42
      days, in a transperineally implanted dog up to 12 months and in 8 transperineally
      implanted pigs up to 6 months. Upon inflation in situ the balloon separated the
      tissues, remained inflated for several months and subsequently biodegraded. No
      systemic or local toxicity was noted, as shown by histopathology. Device
      insertion into the perineal area using a dedicated introductory kit was
      convenient and feasible. Three-month followup in irradiated pigs that received 15
      Gy in 3 fractions 1 week apart showed a stable balloon position with no local or
      systemic side effects. CONCLUSIONS: This novel device was safe and effective for
      its intended use of separating tissues for a desired duration. A clinical study
      will commence to evaluate the safety and efficacy of this device during
      irradiation in patients with prostate cancer.

PMID- 19157459
TI  - Ureteroarterial fistula following laser endopyelotomy.

PMID- 19157460
TI  - MicroRNA-143 as a tumor suppressor for bladder cancer.
AB  - PURPOSE: We investigated the expression and involvement of miRNA in bladder
      cancer. MATERIALS AND METHODS: An miRNA array was used to examine the
      differential expression of miRNA in tumor tissues and normal matched controls.
      The expression of miRNA-143 was confirmed by Northern blot and real-time
      polymerase chain reaction. The functional role of miRNA-143 in bladder cancer was
      studied by examining cell proliferation and oncogene expression after miRNA-143
      transfection into 2 transitional carcinoma cell lines. RESULTS: miRNA profiling
      of human bladder cancer and matched normal urothelial epithelium controls
      revealed that 37 miRNAs were up-regulated and 38 were down-regulated in cancer
      tissues, of which the expression of miRNA-143 was 13.7 times lower in tumor than
      in the matched control. Consistent with microarray data, Northern blot analysis
      and real-time polymerase chain reaction confirmed that miRNA-143 expression was
      significantly down-regulated in bladder tumor tissues compared with normal
      adjacent tissues. The expression of miRNA-143 was not detected in the 2 human
      bladder cancer cell lines EJ and T24. Interestingly miRNA-143 transfection into
      EJ and T24 cells significantly inhibited cell proliferation. RAS protein
      expression in cancer tissues was much higher than in adjacent controls.
      Consistently RAS protein expression was also significantly decreased in miRNA-143
      transfected cells compared with nonspecific miRNA transfected cells. CONCLUSIONS:
      miRNAs are differentially expressed in bladder cancer tissues. miRNA-143 may
      function as a tumor suppressor in bladder transitional cell carcinoma.

PMID- 19157461
TI  - Erythropoietin attenuates renal injury in an experimental model of rat unilateral
      ureteral obstruction via anti-inflammatory and anti-apoptotic effects.
AB  - PURPOSE: Erythropoietin was recently shown to exert important cytoprotective and
      anti-apoptotic effects in injury models of the brain, heart and kidney. We
      examined whether erythropoietin also attenuates renal injury in a rat model of
      unilateral ureteral obstruction via anti-apoptotic and anti-inflammatory actions.
      MATERIALS AND METHODS: We divided Sprague-Dawley rats (Korea Research Institute
      of Bioscience and Biotechnology, Daejeon, Korea) into 4 groups, including 1
      vehicle treated with sham operation, 2-vehicle treated with unilateral ureteral
      obstruction for 3 days, 3-erythropoietin treatment with sham operation and 4
      erythropoietin treatment for unilateral ureteral obstruction for 3 days. The
      erythropoietin treatment dose was 3,000 IU/kg per day intraperitoneally,
      administered daily. We compared competitive reverse transcriptase-polymerase
      chain reaction data on transforming growth factor-beta, tumor necrosis factor
      alpha, monocyte chemoattractant protein-1, osteopontin, Fas and Bcl-2.
      Furthermore, we examined Western blots for caspase-3 and light microscopy
      findings with hematoxylin and eosin staining. We applied immunohistochemistry for
      transforming growth factor-beta, ED-1 and caspase-3, and TUNEL in each group.
      RESULTS: Transforming growth factor-beta, tumor necrosis factor-alpha, monocyte
      chemoattractant protein-1, osteopontin and Fas mRNA levels in the erythropoietin
      treated, unilateral ureteral obstruction group were significantly lower than in
      the obstruction only group. The Bcl-2 mRNA level in the erythropoietin treated
      obstruction group was significantly higher than in the obstruction only group.
      Caspase-3 activity in the erythropoietin treated obstruction group was
      significantly lower than in the obstruction only group. On light microscopy
      interstitially infiltrated inflammatory cells were significantly decreased in the
      erythropoietin treated obstruction group compared to the obstruction only group.
      On immunohistochemistry the erythropoietin treated obstruction group showed
      significantly fewer reactions for transforming growth factor-beta, ED-1 and
      caspase-3 compared to the obstruction only group. Erythropoietin treatment in
      rats with unilateral ureteral obstruction significantly decreased the number of
      TUNEL positive cells. CONCLUSIONS: Erythropoietin exerts renoprotective effects
      in an experimental unilateral ureteral obstruction rat model via anti-apoptotic
      and anti-inflammatory actions.

PMID- 19157462
TI  - A numerical oil spill model based on a hybrid method.
AB  - The purpose of this paper is the development of a hybrid particle
      tracking/Eulerian-Lagrangian approach for the simulation of spilled oil in
      coastal areas. Oil discharge from the source is modeled by the release of
      particles. When the oil slick thickness or the oil concentration reaches a
      critical value, particles are mapped on slick thickness or node concentrations,
      and the calculations proceed in the Eulerian-Lagrangian mode. To acquire accurate
      environment information, the model is coupled with the 3-D free-surface
      hydrodynamics model (POM) and the third-generation wave model (SWAN). By
      simulating the oil processes of spreading, advection, turbulent diffusion,
      evaporation, emulsification, dissolution and shoreline deposition, it has the
      ability to predict the horizontal movement of surface oil slick, the vertical
      distribution of oil particles, the concentration in the water column and the mass
      balance of spilled oil. An accidental oil release near Dalian coastal waters is
      simulated to validate the developed model. Compared with the satellite images of
      oil slicks on the surface, the numerical results indicate that the model has a
      reasonable accuracy.

PMID- 19157463
TI  - Potential link between exposure to fungicides chlorothalonil and mancozeb and
      haemic neoplasia development in the soft-shell clam Mya arenaria: a laboratory
      experiment.
AB  - The aetiology of haemic neoplasia (HN) is unknown, so far but many causative
      factors are suggested such as viral, pollution and genetics. The aim of this
      study was to determine if, under chronic exposure, two major pesticides
      (chlorothalonil and mancozeb) which are used in potato production could induce HN
      in soft-shell clams (Mya arenaria). Short-term experiments with acute exposure
      were also performed. Clams were collected from an epizootic site (North River,
      PEI) and from a site free of the disease (Magdalen Islands, Quebec). The
      tetraploid level of haemocytes was assessed by flow cytometry for each clam to
      determine the HN status. The bioaccumulation of pesticides in tissues was
      quantified by gas chromatography/mass spectrometry (GC/MS) for chlorothalonil
      while mancozeb and manganese were quantified by inductively coupled plasma-mass
      spectrometer (ICP/MS). Long term exposure to fungicide Bravo 500((R)) did not
      induce high tetraploid levels on negative calm from North River and the analysis
      of the digestive gland and the mantle did not reveal any detectable level of
      chlorothalonil. In the Manzate 200 DF((R)), some clams revealed high level of
      tetraploid cells but no difference were observed between the treatments and the
      control. The analysis of the digestive gland and the mantle for manganese did not
      highlight any significant difference in tissue concentration (p=0.05). For the
      acute exposure, chlorothalonil analysis showed that the active ingredient is
      distributed between four chlorinated compounds: 99.5% for chlorothalonil isomers,
      0.4% for pentachlorothalonil and 0.1% for trichlorothalonil isomers. For a 72 h
      experiment, the accumulation was within 4h; the higher tissue concentration of
      chlorothalonil was 59.2 microg g(-1) in the mantle after 48 h, following by a
      decrease to an undetectable level at the end. For the manganese, the accumulation
      was detected after 4h; the higher tissue concentration was 48.8 microg g(-1) in
      the mantle after 24h and, over the following 48 h, the accumulation decreased
      until the end of the trial. Based on the data, the accumulation of these
      fungicides seems to be transitory. Chlorothalonil and mancozeb are both oxidative
      stress promoters and could have induced cell dysfunction while in the tissue.
      Study on the effect of these fungicides on the p53 protein system is an example
      of strategy that would provide information on cellular events promoting
      neoplasia.

PMID- 19157464
TI  - Evaluation of the health status of a coastal ecosystem in southeast Mexico:
      Assessment of water quality, phytoplankton and submerged aquatic vegetation.
AB  - The coastal environment of the Yucatan Peninsula (SE, Mexico) includes a wide
      variety of ecosystems ranging from mangroves to coral reefs, resulting in a
      heterogeneous landscape. Specifically, the marine system is characterized by
      environmental differences which respond to regional and local forcing functions
      such as marine currents and groundwater discharges (GD). Such functional
      characteristics were used here to define four subregions across the Yucatan coast
      and diagnose the health status of this coastal marine ecosystem. To achieve this
      goal, we conducted an analysis and integration of water quality variables, an
      eutrophic assessment, evaluated changes in submerged aquatic vegetation (SAV),
      and analyzed the community structure and distribution of harmful phytoplankton.
      The first step was to determine the reference values for each subregion based on
      data previously collected from 2002 to 2006 along the coast of Yucatan, 200m
      offshore. The trophic index (TRIX) and Canadian index for aquatic life (CCMEWQI)
      were used to diagnose each subregion and then the ASSETS approach was conducted
      for Dzilam and Progreso, sampling localities on each end of the health status
      continuum (those with the best and worst conditions). Overall, results indicated
      that the marine coastal ecosystem of Yucatan is in good condition; however,
      differences were observed between subregions that can be attributed to local
      forcing functions and human impacts. Specifically, the central region (zone HZII,
      Progreso-Telchac) showed symptoms of initial eutrophication due to nutrient
      inputs from human activities. The eastern region (zone HZ III, Dzilam-Las Bocas)
      showed a meso-eutrophic condition linked to natural groundwater discharges, while
      the other two subregions western (zone HZI Celestun-Palmar) and caribbean (zone
      HZ IV Ria Lagartos-El Cuyo) exhibited symptoms of oligo-mesotrophic condition.
      These findings may be considered baseline information for coastal ecosystem
      monitoring programs in Yucatan, and the approach used could be replicated for
      other coastal areas.

PMID- 19157465
TI  - Evaluating crude oil chemical dispersion efficacy in a flow-through wave tank
      under regular non-breaking wave and breaking wave conditions.
AB  - Testing dispersant effectiveness under conditions similar to that of the open
      environment is required for improvements in operational procedures and the
      formulation of regulatory guidelines. To this end, a novel wave tank facility was
      fabricated to study the dispersion of crude oil under regular non-breaking and
      irregular breaking wave conditions. This wave tank facility was designed for
      operation in a flow-through mode to simulate both wave- and current-driven
      hydrodynamic conditions. We report here an evaluation of the effectiveness of
      chemical dispersants (Corexit EC9500A and SPC 1000) on two crude oils (Medium
      South American [MESA] and Alaska North Slope [ANS]) under two different wave
      conditions (regular non-breaking and plunging breaking waves) in this wave tank.
      The dispersant effectiveness was assessed by measuring the water column oil
      concentration and dispersed oil droplet size distribution. In the absence of
      dispersants, nearly 8-19% of the test crude oils were dispersed and diluted under
      regular wave and breaking wave conditions. In the presence of dispersants, about
      21-36% of the crude oils were dispersed and diluted under regular waves, and 42
      62% under breaking waves. Consistently, physical dispersion under regular waves
      produced large oil droplets (volumetric mean diameter or VMD > or = 300 microm),
      whereas chemical dispersion under breaking waves created small droplets (VMD < or
      = 50 microm). The data can provide useful information for developing better
      operational guidelines for dispersant use and improved predictive models on
      dispersant effectiveness in the field.

PMID- 19157466
TI  - Cyanogenic and non-cyanogenic pyridone glucosides from Acalypha indica
      (Euphorbiaceae).
AB  - Seven cyanopyridone derivatives and one corresponding seco compound have been
      isolated from a methanolic extract of the inflorescences and leaves of Acalypha
      indica L. (Euphorbiaceae). The absolute configuration of the main cyanogenic
      glucoside acalyphin, (-)-(5R,6S)-5-cyano-5-beta-d-glucopyranosyloxy-6-hydroxy-4
      methoxy-1-methyl-2(5,6-dihydro)-pyridone, was deduced from an X-ray
      crystallographic study. In addition, the 6R-epimer of acalyphin, epiacalyphin,
      and the corresponding pair of N-demethyl derivatives were isolated. The
      corresponding amide of acalyphin and a 1',2'-glucosyl-fused epiacalyphin amide
      were isolated from air-dried material. Structural elucidation was performed by
      means of (1)H and (13)C NMR-spectra, chiroptical methods such as CD-spectroscopy
      and optical rotation. Two further corresponding derivatives, an aromatized
      compound and an open-chain structure, were isolated from the aqueous phase.

PMID- 19157467
TI  - Identifying humanitarian crises in population surveillance field sites: simple
      procedures and ethical imperatives.
AB  - OBJECTIVES: Effective early warning systems of humanitarian crises may help to
      avert substantial increases in mortality and morbidity, and prevent major
      population movements. The Butajira Rural Health Programme (BRHP) in Ethiopia has
      maintained a programme of epidemiological surveillance since 1987. Inspection of
      the BRHP data revealed large peaks of mortality in 1998 and 1999, well in excess
      of the normally observed year-to-year variation. Further investigation and
      enquiry revealed that these peaks related to a measles epidemic, and a serious
      episode of drought and consequent food insecurity that went undetected by the
      BRHP. This paper applies international humanitarian crisis threshold definitions
      to the BRHP data in an attempt to identify suitable mortality thresholds that may
      be used for the prospective detection of humanitarian crises in population
      surveillance sites in developing countries. STUDY DESIGN: Empirical investigation
      using secondary analysis of longitudinal population-based cohort data. METHODS:
      The daily, weekly and monthly thresholds for crises in Butajira were applied to
      mortality data for the 5-year period incorporating the crisis periods of 1998
      1999. Days, weeks and months in which mortality exceeded each threshold level
      were identified. Each threshold level was assessed in terms of prospectively
      identifying the true crisis periods in a timely manner whilst avoiding false
      alarms. RESULTS: The daily threshold definition is too sensitive to accurately
      detect impending or real crises in the population surveillance setting of the
      BRHP. However, the weekly threshold level is useful in identifying important
      increases in mortality in a timely manner without the excessive sensitivity of
      the daily threshold. The weekly threshold level detects the crisis periods
      approximately 2 weeks before the monthly threshold level. CONCLUSION: Mortality
      measures are highly specific indicators of the health status of populations, and
      simple procedures can be used to apply international crisis threshold definitions
      in population surveillance settings for the prospective detection of important
      changes in mortality rate. Standards for the timely use of surveillance data and
      ethical responsibilities of those responsible for the data should be made
      explicit to improve the public health functioning of current sentinel
      surveillance methodologies.

PMID- 19157468
TI  - Life expectancy and age-period-cohort effects: analysis and projections of
      mortality in Spain between 1977 and 2016.
AB  - OBJECTIVES: This study aimed to: (1) assess Spanish mortality trends between 1977
      and 2001 and their impact on life expectancy; and (2) assess the differences in
      life expectancy between men and women for the period 2002-2016. STUDY DESIGN:
      Time trends study using age-period-cohort (APC) analysis. METHODS: A Bayesian APC
      model was fitted to describe Spanish mortality rates for the period 1977-2001 and
      to project Spanish mortality rates for 2002-2016. Life expectancy was predicted
      through Chiang's method using projected mortality rates. RESULTS: There was a
      significant cohort effect for Spanish mortality, showing a slight increase in
      mortality among men aged 20-39 years between 1986 and 1997 (birth cohorts 1940
      1970). Life expectancy is expected to increase by approximately 0.5% in men and
      women between 1977 and 2016 (1 year per 5-year period). Life expectancy for males
      born between 2012 and 2016 will be 77.15 years, compared with 84.95 years for
      females born during the same period. CONCLUSIONS: The rising trend in mortality
      among the 1940-1970 cohorts may be due to the increased risk of avoidable causes
      of death related to acquired immunodeficiency syndrome, traffic accidents, and
      drug and alcohol abuse during the mid 1980s. The decline in mortality rates in
      recent years could lead to a mean increase in life expectancy of 1 year per 5
      year period in both genders between 2002 and 2016. An increase in life expectancy
      for women and a levelling off for men is expected for age groups older than 79
      years.

PMID- 19157469
TI  - Thinking the unthinkable: could the increasing misuse of prescription opioids
      among street drug users offer benefits for public health?

PMID- 19157471
TI  - Distribution of latent bovine herpesvirus 2 DNA in tissues of experimentally
      infected sheep.
AB  - The biology of latent infection by bovine herpesvirus 2 (BoHV-2), the agent of
      mammillitis in cows, remains largely unknown. We herein report attempts to
      reactivate the latent infection and investigated the sites of BoHV-2 latency in
      experimentally infected sheep. Ewes inoculated with BoHV-2 in the udder's skin
      shed virus for up to five days, developed mammillitis and seroconverted. However,
      attempts to reactivate latent infection by dexamethasone administration at day 40
      pi failed. Nevertheless, viral DNA--and not infectious virus--was detected by PCR
      in several nerve ganglia and/or regional lymph nodes (LNs) of all animals at day
      40 post-reactivation. Likewise, lambs previously inoculated with BoHV-2 in the
      nose harbored latent viral DNA in trigeminal ganglia, tonsils and regional LNs.
      These results demonstrate that BoHV-2 establishes latent infection in nerve
      ganglia and in regional lymphoid tissues, yet virus reactivation is not easily
      achieved by standard protocols used.

PMID- 19157472
TI  - [French national survey on neurology resident training].
AB  - BACKGROUND: Over the past 20 years, the neurology specialty has changed because
      of the explosion of information and new treatment modalities that became
      available, and has consequently become more complex and diversified. The
      satisfaction of residents concerning their training and the competencies that
      they acquire has never been thoroughly assessed in France. METHODS: We conducted
      a national survey in order to assess (1) the methods for training and validation;
      (2) the level of knowledge that residents perceived to have acquired in different
      domains; and (3) their satisfaction towards training and their wishes. RESULTS:
      One hundred and eight residents replied to the survey. The main sources of
      training were local teaching (74%), personal work (61%), scientific (57%) and
      didactic (54%) papers. Residents seemed unable to acquire knowledge on all
      domains of the curriculum established at a national level, particularly for
      neurophysiology, neuropsychology, comatose state and sleep disorders, oncology
      and psychiatry. Even postgraduate year four residents were not fully competent
      with several technical tools, particularly neurophysiological tests. Fifty eight
      percent of residents were satisfied with their training, but 16% were not and 26%
      were half-hearted. Overall the residents were in favor of more standardization in
      their training, national-level certification, and would be keen on having access
      to clinics and the use of a follow-up monitoring chart. CONCLUSION: Our results
      suggest that it would be useful to better identify the competencies that every
      neurologist should acquire and to use appropriate tools to reach these
      objectives.

PMID- 19157474
TI  - [Post-traumatic focal fixed dystonia of the shoulder: a distinctive syndrome with
      speculative mechanisms?].
AB  - INTRODUCTION: Whether post-traumatic focal fixed dystonia has a physiological or
      psychologically-mediated mechanism is discussed. CASE REPORT: We report the case
      of an active 22-year-old soldier with shoulder-fixed dystonia, eight months after
      a fall with minor right-acromioclavicular sprain. CONCLUSION: Psychiatric
      examination and search of complex regional pain syndrome, radicular or accessory
      nerve damage, and genetic predisposition to dystonia are necessary for selecting
      a difficult treatment in these patients.

PMID- 19157473
TI  - Idiopathic intracranial hypertension: a comparison between French and North
      American white patients.
AB  - OBJECTIVE: To compare French and American white patients with idiopathic
      intracranial hypertension (IIH), and to determine prognostic factors associated
      with visual loss. METHODS: Medical records of all consecutive white patients with
      definite IIH seen between 2001 and 2006 in three French tertiary care medical
      centers and one American tertiary medical center were reviewed. Demographics,
      associated clinical features, and visual function at presentation and follow-up
      were collected. French white patients were compared to American white patients.
      RESULTS: One hundred and thirty-four patients (66 French, 68 American) were
      included. American patients were 8.7 times more likely than French patients to
      have visual acuity 20/60 or worse or visual field constriction (95% CI: 2.1-36.1,
      p=0.0001). American patients were treated more aggressively than French patients.
      French patients were older (31 vs. 28 years, p=0.02) and more likely to have
      anemia (20 vs. 2%, p<0.001). American patients had a longer duration of symptoms
      prior to diagnosis (12 vs. 4 weeks, p=0.01) and longer follow-up than French
      patients (26 vs. 11 months, p=0.001). Multivariable analysis found that
      nationality was an independent risk factor for visual loss. French and American
      patients did not differ regarding gender proportion, frequency of obesity, sleep
      apnea, endocrine diseases, or systemic hypertension. Cerebrospinal fluid (CSF)
      opening pressures were similar in both groups. CONCLUSION: American patients with
      IIH had worse visual outcomes than French patients despite more aggressive
      treatment. These differences are not explained by differences in previously known
      risk factors.

PMID- 19157475
TI  - Poverty, inequality and health: the challenge of the double burden of disease in
      a non-profit hospital in rural Ethiopia.
AB  - This study was aimed at describing disease patterns in a rural zone of Oromiya
      region, Ethiopia through a retrospective analysis of discharge records for 22,377
      inpatients of St. Luke Hospital, Wolisso, Ethiopia in the period 2005-2007. The
      leading cause of admission was childbirth, followed by injuries, malaria and
      pneumonia. Injuries were the leading cause of in-hospital deaths, followed by
      pneumonia, malaria, cardiovascular disease and AIDS. Vulnerable groups (infants,
      children and women) accounted for 73.3% of admissions. Most of the disease burden
      resulted from infectious diseases, the occurrence of which could be dramatically
      reduced by cost-effective preventive and curative interventions. Furthermore, a
      double burden of disease is already emerging at the early stage of the
      epidemiological transition, with a mix of persistent, emerging and re-emerging
      infectious diseases and increasing prevalence of chronic conditions and injuries.
      This will lead to fundamental changes in the volume and composition of demand for
      healthcare, with a more complex case mix and more costly service utilization
      patterns. The challenge is to address the double burden of disease, while
      focusing on poverty-related conditions and targeting vulnerable groups.
      Monitoring disease and service utilization patterns through routine hospital
      information systems can provide sustainable, low-cost support for evidence-based
      health practice.

PMID- 19157476
TI  - Material property estimates from ultrasound attenuation in fibre suspensions.
AB  - An investigation of a new method for measuring fibre material properties from
      ultrasonic attenuation in a dilute suspension of synthetic fibres of uniform
      geometry is presented. The method is based on inversely solving an ultrasound
      scattering and absorption model of suspended fibres in water for the material
      properties of the fibres. Experimental results were obtained from three
      suspensions of nylon 66 fibres each with different fibre diameters. A forward
      solution to the model with reference material values is compared to experimental
      data to verify the model's behaviour. Estimates of the shear and Young's modulus,
      the compressional wave velocity, Poisson's ratio and loss tangent from nylon 66
      fibres are compared to data available from other sources. Experimental data
      confirms that the model successfully predicts that the resonance features in the
      frequency response of the attenuation are a function of diameter. Consistent
      estimated values for the compressional wave velocity and the Poisson's ratio were
      found to be difficult to obtain but in combination gave values of shear modulus
      within previously reported values and with low sensitivity to noise. Young's
      modulus was underestimated by 54% but was consistent and had low sensitivity to
      noise. The underestimation is believed to be caused by the assumption of
      isotropic material used in the model. Additional tests on isotropic fibre would
      confirm this. Further analysis of the model sensitivity and the reasons for the
      resonance features are required.

PMID- 19157477
TI  - Structure, attachment and entry of polyoma- and papillomaviruses.
AB  - Polyoma- (PY) and Papillomavirus (PV) virions have remarkable structural
      equivalence although no discernable sequence similarities among the capsid
      proteins can be detected. Their similarities include the overall surface
      organization, the presence of 72 capsomeres composed of five molecules of the
      major capsid proteins, VP1 and L1, respectively, the structure of the core
      segment of capsomeres with classical antiparallel "jelly roll" beta strands as
      the major feature, and the linkage of neighboring capsomeres by invading C
      terminal arms. Differences include the size of surface exposed loops that contain
      the dominant neutralizing epitopes, the details of the intercapsomeric
      interactions, and the presence of 2 or 1 minor capsid proteins, respectively.
      These differences may affect the dramatic differences observed in receptor
      binding and internalization pathways utilized by these viruses, but as detailed
      later even structural differences cannot completely explain receptor and pathway
      usage. In recent years, technical advances aiding the study of entry processes
      have allowed the identification of novel endocytic compartments and an
      appreciation of the links between endocytic pathways that were previously thought
      to be completely separable. This review is intended to highlight recent advances
      in our understanding of virus receptor interactions and their consequences for
      endocytosis and intracellular trafficking.

PMID- 19157479
TI  - HBx protein induces expression of MIG and increases migration of leukocytes
      through activation of NF-kappaB.
AB  - Elevated expression of monokine induced by the interferon-gamma (MIG) has been
      shown in HBV carriers, and it is involved in the infiltration of inflammatory
      cells and liver damage after HBV infection. However, the molecular mechanisms by
      which HBV-induced MIG expression have not been characterized. Our results
      indicated that HBx protein induced MIG expression in a dose-dependent manner.
      Such increase was due to the direct binding of NF-kappaB to the MIG promoter. By
      luciferase, chromatin immunoprecipitation and electrophoretic mobility shift
      assays, we demonstrated that the NF-kappaB binding site at positions -147 was
      essential for transcriptional activation of MIG promoter by HBx protein.
      Chemotaxis assay showed that the up-regulation of MIG protein levels enhanced the
      migration of peripheral blood lymphocytes (PBLs), and inhibition of NF-kappaB
      significantly decreased the chemotaxis activity. Our findings provide a new
      insight into how leukocytes migrate to liver, and disclose a new regulatory
      mechanism of MIG expression after HBV infection.

PMID- 19157478
TI  - The Polyomaviridae: Contributions of virus structure to our understanding of
      virus receptors and infectious entry.
AB  - This review summarizes the field's major findings related to the characterization
      of polyomavirus structures and to the characterization of virus receptors and
      mechanisms of host cell invasion. The four members of the family that have
      received the most attention in this regard are the mouse polyomavirus (mPyV), the
      monkey polyomavirus SV40, and the two human polyomaviruses, JCV and BKV. The
      structures of both the mPyV and SV40 alone and in complex with receptor fragments
      have been solved to high resolution. The majority of polyomaviruses recognize
      terminal sialic acid in either an alpha2,3 linkage or an alpha2,6 linkage to the
      underlying galactose. Studies on virus structure, receptor utilization and
      mechanisms of entry have led to new insights into how these viruses interact in
      an active way with cells to ensure the nuclear delivery and expression of their
      genomes. Critical work on virus entry has led to the discovery of a pH neutral
      endocytic compartment that accepts cargo from caveolae and to novel roles for
      endoplasmic reticulum (ER) associated factors in virus uncoating and penetration
      of ER membranes. This review will summarize the major findings and compare and
      contrast the mechanisms used by these viruses to infect cells.

PMID- 19157480
TI  - Role of a heterologous retroviral transport element in the development of genetic
      complementation assay for mouse mammary tumor virus (MMTV) replication.
AB  - The mouse mammary tumor virus (MMTV) is a type B retrovirus that is unique from
      other retroviruses in having multiple "tissue specific" and "hormone inducible"
      promoters. This unique feature has lead to the increasing interest in studying
      the biology of MMTV replication with the ultimate goal of developing MMTV based
      vectors for potentially targeted human gene therapy. In this report, we describe,
      for the first time, the establishment of an in vivo genetic complementation assay
      to study various aspects of MMTV replication. In the assay described here, the
      function of MMTV Rem/RmRE regulatory pathway has been successfully substituted by
      a heterologous retroviral constitutive transport element (CTE) from Mason Pfizer
      Monkey Virus (MPMV) for mature MMTV particle production. Our results revealed
      that in the absence of MPMV CTE or Rem/RmRE, RNA transcribed from MMTV Gag-Pol
      expression plasmids were efficiently transported to the cytoplasm. However, the
      presence of CTE was indispensable for Gag-Pol protein expression. In addition, we
      report the development of MMTV based vectors in which the packageable RNA was
      transcribed either from MMTV LTR or from a chimeric LTR, which could successfully
      be packaged and propagated by particles produced from MMTV Gag-Pol expression
      plasmids containing a heterologous transport element. The role of MPMV CTE in the
      transport of MMTV transfer vector RNA was not found to be significant.
      Development of such an assay should not only shed light on how MMTV regulates its
      gene expression, but also should provide additional molecular tools for
      delineating the packaging determinants for MMTV, which is imperative for the
      development of novel vectors for targeted and inducible gene therapy.

PMID- 19157481
TI  - High replication fitness and transmission efficiency of HIV-1 subtype C from
      India: Implications for subtype C predominance.
AB  - HIV-1 subtype C has been the predominant subtype throughout the course of the HIV
      1 epidemic in India regardless of the geographic region of the country. In an
      effort to understand the mechanism of subtype C predominance in this country, we
      have investigated the in vitro replication fitness and transmission efficiency of
      HIV-1 subtypes A and C from India. Using a dual infection growth competition
      assay, we found that primary HIV-1 subtype C isolates had higher overall relative
      fitness in PBMC than subtype A primary isolates. Moreover, in an ex vivo cervical
      tissue derived organ culture, subtype C isolates displayed higher transmission
      efficiency across cervical mucosa than subtype A isolates. We found that higher
      fitness of subtype C was not due to a trans effect exerted by subtype C infected
      PBMC. A half genome A/C recombinant clone in which the 3' half of the viral
      genome of subtype A was replaced with the corresponding subtype C3' half, had
      similar replicative fitness as the parental subtype A. These results suggest that
      the higher replication fitness and transmission efficiency of subtype C virus
      compared to subtype A virus from India is most probably not due to the envelope
      gene alone and may be due to genes present within the 5' half of the viral genome
      or to a more complex interaction between the genes located within the two halves
      of the viral genome. These data provide a model to explain the asymmetric
      distribution of subtype C over other subtypes in India.

PMID- 19157482
TI  - Vaccination with virus-like particles protects mice from lethal infection of Rift
      Valley Fever Virus.
AB  - Rift Valley Fever virus (RVFV) regularly accounts for severe and often lethal
      outbreaks among livestock and humans in Africa. Safe and effective veterinarian
      and human vaccines are highly needed. We present evidence that administration of
      RVF virus-like particles (VLPs) induces protective immunity in mice. In an
      accompanying paper, (Habjan, M., Penski, N., Wagner, V., Spiegel, M., Overby,
      A.K., Kochs, G., Huiskonen, J., Weber, F., 2009. Efficient production of Rift
      Valley fever virus-like particles: the antiviral protein MxA can inhibit primary
      transcription of Bunyaviruses. Virology 385, 400-408) we report the production of
      these VLPs in mammalian cells. After three subsequent immunizations with 1x10(6)
      VLPs/dose, high titers of virus-neutralizing antibodies were detected; 11 out of
      12 mice were protected from challenge and only 1 out of 12 mice survived
      infection in the control groups. VLP vaccination efficiently suppressed
      replication of the challenge virus, whereas in the control animals high RNA
      levels and increasing antibody titers against the nucleocapsid protein indicated
      extensive viral replication. Our study demonstrates that the RVF VLPs are highly
      immunogenic and confer protection against RVFV infection in mice. In the test
      groups, the vaccinated mice did not exhibit any side effects, and the lack of
      anti-nucleocapsid protein antibodies serologically distinguished vaccinated
      animals from experimentally infected animals.

PMID- 19157483
TI  - Controlling soluble iron and manganese in a water-supply reservoir using
      hypolimnetic oxygenation.
AB  - Soluble metals such as iron (Fe) and manganese (Mn) often reach problematic
      levels in water-supply reservoirs during summer stratification following the
      onset of hypolimnetic hypoxia. The behavior of soluble and particulate Fe and Mn
      was studied following the installation of a hypolimnetic oxygenation system in
      Carvins Cove Reservoir, a water-supply impoundment managed by the Western
      Virginia Water Authority. During oxygenation, manganese concentrations were very
      low in the bulk hypolimnion (<0.05 mg l(-1)), but high concentrations (>2.0 mg l(
      1)) were still observed in the benthic region close to the sediment, despite near
      sediment dissolved oxygen concentrations in excess of 5.0 mg l(-1). Oxygenation
      appears to affect the location of the oxic/anoxic boundary sufficiently to
      restrict substantial transport of soluble Mn to the bulk water of the
      hypolimnion. However, the position of the oxic/anoxic boundary was not uniformly
      affected along the reservoir bottom, allowing horizontal transport of soluble Mn
      from higher elevations in contact with hypoxic sediments. During one summer, when
      the oxygen system was turned off for a month, the soluble Mn in the bulk
      hypolimnion increased substantially. Oxygen concentrations were quickly restored
      after the system was turned back on, but elevated levels of soluble Mn persisted
      until the sedimentation rate of detritus through the hypolimnion increased. When
      operated without interruption, the oxygenation system was able to reduce the bulk
      average hypolimnion soluble Mn concentration by up to 97%, indicating that source
      water control of soluble Mn and Fe can be accomplished with hypolimnetic
      oxygenation in water-supply reservoirs.

PMID- 19157484
TI  - A molecular survey on virulence associated genotypes of non-O1 non-O139 Vibrio
      cholerae in aquatic environment of Tehran, Iran.
AB  - Thirty-seven Vibrio cholerae strains were isolated from surface water sources at
      5 different locations in Tehran, Iran during 2006 and were identified as non-O1
      and non-O139 isolates. PCR for SXT element and class 1 integron was positive for
      19% and 5.4% of isolates, respectively. PCR for virulence associated-genes within
      the vibrio pathogenicity island (VPI) gene cluster showed the presence of LJ, int
      and RJ in 8, 59 and 30% of the isolates, respectively. None of the V. cholerae
      isolates contained the toxin encoding genes (ace, zot, ctx) in the CTX genetic
      element. Biochemical fingerprinting using PhPlate system (PhP-RV) was able to
      type all strains and resulted in 8 common types (containing 78% of the isolates)
      and 8 single types (22%). Out of 37 isolates, only 26 isolates were typeable with
      pulsed-field gel electrophoresis (PFGE) producing banding patterns. The results
      presented in this study showed no genotyping correlation between the V. cholerae
      isolated from surface water and the clinical setting which had been reported
      previously by this laboratory. Furthermore, combination of PFGE and PhP-RV
      methods was proved beneficial for non-typeable V. cholerae isolates.

PMID- 19157485
TI  - Evaluation of continuous mesophilic anaerobic sludge digestion after high
      temperature microwave pretreatment.
AB  - Effect of microwave pretreatment (MW) high temperature (175 degrees C) and MW
      intensity to waste activated sludge digested with acclimatized inoculum in single
      and dual-stage semi-continuous mesophilic anaerobic digesters at different
      sludge retention times (SRTs) (20, 10 and 5 days) were investigated. MW
      pretreatment led to similar sludge stabilization at low SRTs (5 and 10 days).
      Although lowering MW intensity slightly improved sludge solubilization, it had a
      negative effect on digestion at low SRTs. Single-stage digesters with MW
      pretreatment surpass dual-stage digesters performances.

PMID- 19157486
TI  - Combination of one-dimensional TiO(2) nanowire photocatalytic oxidation with
      microfiltration for water treatment.
AB  - This paper proposed the fabrication of two different diameter one-dimensional
      TiO2 nanowires, 10 nm TNW10 and 20-100 nm TNW20, via hydrothermal process using
      different alkaline sources. TNW10 and TNW20 were used as photocatalysts for the
      degradation of humic acid (HA), the major natural organic matters (NOMs) in
      surface and ground water, followed by microfiltration. The evaluation of
      photocatalytic activities of them showed that TNW10 was superior to the
      commercial P25 TiO2 while TNW20 was as good as P25. The membrane filtration
      verified that the two types of nanowires could be completely reclaimed. The
      membrane fouling caused by TNW10 and TNW20 was much less than that of P25 due to
      more porous cake and less pore plugging. No apparent decrease on their
      photocatalytic activity was observed in repeated reuse experiments. These one
      dimensional TiO2 nanowires would provide a new route for the combination of
      photocatalytic oxidation and membrane filtration for water treatment.

PMID- 19157487
TI  - Absorption of the selenite anion from aqueous solutions by thermally activated
      layered double hydroxide.
AB  - The presence of selenite or selenate in potable water is a health hazard
      especially when consumed over a long period of time. Its removal from potable
      water is of importance. This paper reports technology for the removal of selenite
      from water through the use of thermally activated layered double hydroxides.
      Mg/Al hydrotalcites with selenite in the interlayer were prepared at different
      times from 0.5 to 20 h through ion exchange. X-ray diffraction of the MgAlSeO3
      hydrotalcites indicates that the selenite anion entered the interlayer spacing of
      Mg/Al hydrotalcite and MgAlSeO3 hydrotalcite was formed. Raman spectra proved the
      presence of selenite anion in the hydrotalcite interlayer as the counter anion.
      The band intensity and width of MgAlSeO3 hydrotalcite in the region of 3800-3000
      cm(-1) increase with the adsorption of selenite by the Mg/Al hydrotalcite. The
      characteristic bands of free selenite anions in the MgAlSeO3 hydrotalcites are
      located between the region between 850 and 800 cm(-1). The Raman spectra of the
      lower wave number region of 550-500 cm(-1) show a shift toward higher wave
      numbers with adsorption of the selenite. An estimation of the amount of selenite
      anion removed by the thermally activated layered double hydroxide was obtained
      through the measurement of the intensity of the selenite Raman bands at 814 and
      835 cm(-1) resulting from the amount of selenite anion remaining in solution.
      Thermally activated LDHs provide a mechanism for removing selenite anions from
      aqueous solutions.

PMID- 19157488
TI  - Fault tree analysis for integrated and probabilistic risk analysis of drinking
      water systems.
AB  - Drinking water systems are vulnerable and subject to a wide range of risks. To
      avoid sub-optimisation of risk-reduction options, risk analyses need to include
      the entire drinking water system, from source to tap. Such an integrated approach
      demands tools that are able to model interactions between different events. Fault
      tree analysis is a risk estimation tool with the ability to model interactions
      between events. Using fault tree analysis on an integrated level, a probabilistic
      risk analysis of a large drinking water system in Sweden was carried out. The
      primary aims of the study were: (1) to develop a method for integrated and
      probabilistic risk analysis of entire drinking water systems; and (2) to evaluate
      the applicability of Customer Minutes Lost (CML) as a measure of risk. The
      analysis included situations where no water is delivered to the consumer
      (quantity failure) and situations where water is delivered but does not comply
      with water quality standards (quality failure). Hard data as well as expert
      judgements were used to estimate probabilities of events and uncertainties in the
      estimates. The calculations were performed using Monte Carlo simulations. CML is
      shown to be a useful measure of risks associated with drinking water systems. The
      method presented provides information on risk levels, probabilities of failure,
      failure rates and downtimes of the system. This information is available for the
      entire system as well as its different sub-systems. Furthermore, the method
      enables comparison of the results with performance targets and acceptable levels
      of risk. The method thus facilitates integrated risk analysis and consequently
      helps decision-makers to minimise sub-optimisation of risk-reduction options.

PMID- 19157489
TI  - Present limitations and future prospects of stable isotope methods for nitrate
      source identification in surface- and groundwater.
AB  - Nitrate (NO3(-)) contamination of surface- and groundwater is an environmental
      problem in many regions of the world with intensive agriculture and high
      population densities. Knowledge of the sources of NO3(-) contamination in water
      is important for better management of water quality. Stable nitrogen (delta15N)
      and oxygen (delta18O) isotope data of NO3(-) have been frequently used to
      identify NO3(-) sources in water. This review summarizes typical delta15N- and
      delta18O-NO3(-) ranges of known NO3(-) sources, interprets constraints and future
      outlooks to quantify NO3(-) sources, and describes three analytical techniques
      ("ion-exchange method", "bacterial denitrification method", and "cadmium
      reduction method") for delta15N- and delta18)O-NO3(-) determination. Isotopic
      data can provide evidence for the presence of dominant NO3(-) sources. However,
      quantification, including uncertainty assessment, is lacking when multiple NO3(-)
      sources are present. Moreover, fractionation processes are often ignored, but may
      largely constrain the accuracy of NO3(-) source identification. These problems
      can be overcome if (1) NO3(-) isotopic data are combined with co-migrating
      discriminators of NO3(-) sources (e.g. (11)B), which are not affected by
      transformation processes, (2) contributions of different NO3(-) sources can be
      quantified via linear mixing models (e.g. SIAR), and (3) precise, accurate and
      high throughput isotope analytical techniques become available.

PMID- 19157490
TI  - Ozonation kinetics of winery wastewater in a pilot-scale bubble column reactor.
AB  - The degradation of organic substances present in winery wastewater was studied in
      a pilot-scale, bubble column ozonation reactor. A steady reduction of chemical
      oxygen demand (COD) was observed under the action of ozone at the natural pH of
      the wastewater (pH 4). At alkaline and neutral pH the degradation rate was
      accelerated by the formation of radical species from the decomposition of ozone.
      Furthermore, the reaction of hydrogen peroxide (formed from natural organic
      matter in the wastewater) and ozone enhances the oxidation capacity of the
      ozonation process. The monitoring of pH, redox potential (ORP), UV absorbance
      (254 nm), polyphenol content and ozone consumption was correlated with the
      oxidation of the organic species in the water. The ozonation of winery wastewater
      in the bubble column was analysed in terms of a mole balance coupled with
      ozonation kinetics modeled by the two-film theory of mass transfer and chemical
      reaction. It was determined that the ozonation reaction can develop both in and
      across different kinetic regimes: fast, moderate and slow, depending on the
      experimental conditions. The dynamic change of the rate coefficient estimated by
      the model was correlated with changes in the water composition and oxidant
      species.

PMID- 19157491
TI  - Effects of humic acid on arsenic(V) removal by zero-valent iron from groundwater
      with special references to corrosion products analyses.
AB  - The effects of humic acid (HA) on As(V) removal by zero-valent iron (Fe(0)) from
      groundwater, associated with corrosion products analyses, were investigated using
      batch experiments. It was found that arsenic was rapidly removed from groundwater
      possibly due to its adsorption and co-precipitation with the corrosion products
      of Fe(0). The removal rate of arsenic by Fe(0) was inhibited in the presence of
      HA probably because of the formation of soluble Fe-humate in groundwater which
      hindered the production of iron precipitates. A longer reaction time was then
      required for arsenic removal. Such an influence of HA on arsenic removal
      increased with increasing HA concentration from 5 to 25mgL(-1). The binding
      capacity of HA for dissolved Fe was estimated to be about 0.75mg Femg(-1) HA.
      When the complexation of HA with dissolved Fe was saturated, further corrosion of
      Fe(0) would produce precipitates, which significantly accelerated the removal of
      arsenic from groundwater via adsorption and co-precipitation with the corrosion
      products. Iron (hydr)oxides such as maghemite, lepidocrocite, and magnetite were
      characterized by XRD analyses as the corrosion products, while As(V) was found on
      the surface of these corrosion products as detected by fourier transform infrared
      spectrometry and X-ray photoelectron spectroscopy.

PMID- 19157492
TI  - Sorption of alpha and beta hydrophobic endosulfan in a Vertisol from southeast
      region of Turkey.
AB  - Endosulfan has been applied to control numerous insects in a variety of food and
      non-food crops. Limited information is available on dynamics of this pesticide in
      the soil. The objective of this research was to determine the adsorption
      desorption behavior of the alpha (alpha) and beta (beta) endosulfan in a Vertisol
      from the southeast region of Turkey, where cotton is the main crop in the large
      irrigated lowlands. The alpha and beta endosulfan were adsorbed considerably and
      Freundlich adsorption-desorption isotherms fitted the alpha and beta endosulfan
      data (R(2)>0.98). Freundlich adsorption coefficients (K(f)) for the alpha
      endosulfan ranged between 21.63 and 16.33 while for the beta endosulfan they were
      between 14.01 and 17.98 for the Ap and Bw2 horizons. The difference of K(f)
      values of alpha and beta endosulfan for two horizons were explained with the
      slight difference in the amount of organic matter and clay, but considerable
      difference in Fe contents of the two horizons. Alpha and beta endosulfan K(fd)
      values were 118.03 and 45.81 for the Ap and 48.08 and 68.71 for the Bw2 horizons.
      Higher adsorption and desorption behavior of the endosulfan isomers for the same
      horizon was attributed to poor physical bonding between the endosulfan molecule
      and the surfaces of fundamental soil particles. This fact is thought to increase
      the effective use of endosulfan in agriculture with a possibility of its movement
      to the surface and groundwater in the Vertisol studied.

PMID- 19157493
TI  - Determination of nonylphenol and short-chained nonylphenol ethoxylates in drain
      water from an agricultural area.
AB  - Water samples from agricultural drains were tested for the presence of
      nonylphenol and nonylphenol mono- and diethoxylates. The analytes belong to
      biodegradation products of long-chained nonylphenol ethoxylates, which are used
      as additives in pesticide formulations. Quantification of these analytes was
      performed by HPLC with fluorescence detection after isolation by using multi
      capillary polytetrafluoroethylene (PTFE) trap extraction. This newly developed
      technique allowed obtaining about 90% recovery of these analytes in synthetic
      samples and several percent lower recovery in real samples. Also, no additional
      sample cleaning was needed before chromatographic analysis. The limit of
      quantitation for all the analytes was 0.1 microg L(-1). The nonylphenol,
      nonylphenol mono- and diethoxylates were detected at the concentrations ranging
      from 0.5 to 6.0 microg L(-1), from 0.2 to 0.7 microg L(-1) and from below 0.02 to
      0.4 microg L(-1), respectively. Concentrations of nonylphenol and its derivatives
      were higher in samples taken in spring than in summer.

PMID- 19157494
TI  - Rice fields regulate organochlorine pesticides and PCBs in lagoons of the Nature
      Reserve of Camargue.
AB  - In order to assess pollutant transfer in Camargue ponds from bordering
      agrosystems, a biomonitoring assay was conducted in irrigation and drainage
      channels of rice fields in the Rhone Delta (France). A filter-feeding bivalve,
      the Asian clam, Corbicula fluminea, was used as bioindicator and caged in
      upstream and downstream channels of an area of conventional rice fields. After 6
      weeks incubation, many lipophilic biocides were identified in Corbicula tissues,
      including pesticides used in rice plantations (pretilachlor, oxadiazon),
      pesticides presumed in use in the Rhone basin [diuron and its metabolite 3,4
      dichloroaniline (3,4-DCA)] and organochlorine pesticides (OCPs) banned for
      several decades. In addition, PCBs were highly bioaccumulated in Corbicula.
      Downstream bivalves had significantly lower concentrations of OCPs, PCB and 3,4
      DCA. However, the exposure biomarkers (glutathione S-transferase, catalase and
      propionylcholinesterase) were not correlated with the decreased concentrations.
      The results of this experiment raise several questions concerning the potential
      role of immersed plants in a retention process.

PMID- 19157495
TI  - Development of batch-culture enrichment coupled to molecular detection for
      screening of natural and man-made environments in search of anammox bacteria for
      N-removal bioreactors systems.
AB  - This investigation probed for anammox bacterial populations that would be
      suitable to start-up a biological reactor for N-removal. Samples of sludge and
      sediments from different environments were screened and used as inoculum for
      enrichment of anammox bacteria in batch cultures. Enrichments were monitored in
      order to detect anammox bacteria or their potential activity. Candidatus
      "Brocadia anammoxidans" was successfully enriched, detected, and identified in
      five of the twelve batch cultures. Furthermore, this organism was retrieved for
      the first time from a brackish environment. Wide-range primers used in several
      Polymerase Chain Reaction (PCR) attempts were unable to successfully amplify the
      16S rRNA sequence from anammox populations, but were used to search for
      hypothetical ecological partners of anammox. A nested PCR approach with specific
      primers was also employed since conventional PCR was unable to amplify anammox
      DNA from the inocula of the successful enrichments. However, it was impossible to
      obtain optimal results with the different strategies utilized to improve PCR
      performance (higher annealing temperature or more specific primers), and only the
      primer set Amx368F-Amx820R resulted in an acceptable balance between both
      specificity and sensitivity. Although the enrichment process is relatively slow
      and requires lengthy incubation periods, it proved to be useful as the molecular
      analyses were not sensitive enough to detect anammox in the original samples or
      even after short enrichment periods. Therefore, a batch enrichment procedure
      coupled with molecular techniques was an appropriate approach to achieve
      successful inocula for starting-up anammox biological reactor.

PMID- 19157496
TI  - Mass removal and low-concentration tailing of trichloroethene in freshly-amended,
      synthetically-aged, and field-contaminated aquifer material.
AB  - This study investigates the effect of contaminant aging on the
      sorption/desorption and transport of trichloroethene in a low organic-carbon
      content aquifer material, comparing mass removal and long-term, low-concentration
      elution tailing for field-contaminated, synthetically-aged (contact times of
      approximately four years), and freshly-amended aquifer material. Elution of
      trichloroethene exhibited extensive low-concentration tailing, despite minimal
      retention of trichloroethene by the aquifer material. The observed nonideal
      transport behavior of trichloroethene is attributed primarily to rate-limited
      sorption/desorption, with a smaller contribution from nonlinear sorption. It is
      hypothesized that interaction with physically condensed carbonaceous material,
      comprising 61% of the aquifer material's organic-carbon content, mediates the
      retention behavior of trichloroethene. The elution behavior of trichloroethene
      for the field-contaminated and aged treatments was essentially identical to that
      observed for the fresh treatments. In addition, the results of three independent
      mass-balance analyses, total mass eluted, solvent-extraction analysis of residual
      sorbed mass, and aqueous-phase concentration rebounds following stop-flow
      experiments, showed equivalent recoveries for the aged and fresh treatments.
      These results indicate that long-term contaminant aging did not significantly
      influence the retention and transport of trichloroethene in this low organic
      carbon aquifer material.

PMID- 19157497
TI  - Impact of preozonation on the performance of coagulated flocs.
AB  - Ozone have been widely used as pre-oxidant before conventional water treatment
      processes, while some controversial results on the effects of preozonation on
      coagulation and particle stabilization, have been described. The performance of
      coagulated flocs can be substantially influenced by preozonation which can be
      ascribed to the variation of particles or organic substances in water. In order
      to elucidate the effects of preozonation as an aid in subsequent coagulation, the
      synthetic water composed of kaolin suspension and humic acid was coagulated after
      preozonation. The properties of floc, such as, size, fractal dimension and
      effective density, were investigated using laser light scattering analyzer and
      settling column measurement. It was found that the suspended particles had not
      been destabilized by preozonation as regarding the slight variation of zeta
      potential. As the ozone dose was less than 0.53mgO(3)mg(-1) C, floc size was not
      influenced apparently, while, as the ozone dose increased, the flocs were broken
      and the size decreased remarkably. Specifically, the fractal dimensions of flocs
      increased with increasing ozone dose, resulting in more densely packed flocs with
      low branch structure. Additionally, in terms of settling characteristics, the
      optimal pre-ozone dose was found to be 0.53mgO(3)mg(-1) C, which led to highest
      effective density of flocs with best liquid-solid separation efficiency.

PMID- 19157498
TI  - Prevalence of diabetes and body burdens of polychlorinated biphenyls,
      polybrominated diphenyl ethers, and p,p'-diphenyldichloroethene in Great Lakes
      sport fish consumers.
AB  - Recent studies have demonstrated ubiquitous exposure to persistent organic
      pollutants (POPs) such as p,p'-diphenyldichloroethene (DDE), polychlorinated
      biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). Although several
      studies have noted associations of dioxins, PCBs and DDE with diabetes, the
      results have not always been consistent, with few examining effects of PBDEs or
      simultaneous exposures. The purpose of this study was to determine whether POP
      body burdens are related to diabetes in a cross section of Great Lake sport fish
      consumers. The cohort, which was established in the early 1990s, was recontacted
      in 2004-2005. Serum was collected and tested for DDE, PCBs, PBDEs, hemoglobin A1c
      and lipids, and diabetes diagnosis, demographics and fish consumption were
      assessed by self report. Associations of diabetes with exposures were examined in
      cross sectional data from 2004 to 2005. DDE exposure and dioxin-like mono-ortho
      PCBs were associated with diabetes, but the association of dioxin-like mono-ortho
      PCBs with diabetes did not remain significant after control for DDE exposure.
      Neither the sum of PCBs or years of sport fish consumption were associated with
      prevalent diabetes. There was a non-significant association of PBDEs with
      diabetes only in those with hypothyroid disease. The current study confirms
      previous cross sectional associations of DDE exposure with diabetes. Future
      studies should address biologic pathways by which selective POPs affect glucose
      homeostasis.

PMID- 19157499
TI  - Treponema pallidum distribution patterns in mucocutaneous lesions of primary and
      secondary syphilis: an immunohistochemical and ultrastructural study.
AB  - To study the different patterns of Treponema pallidum distribution in primary and
      secondary syphilis, 34 biopsy specimens of 8 patients with primary and 26 with
      secondary syphilis were assessed. Histopathological features, silver stain, and
      immunohistochemical T pallidum polyclonal antibody expression were investigated.
      The number and distribution of spirochetes were evaluated, and ultrastructural
      studies were performed. Spirochetes were identified with Warthin-Starry stain in
      17 specimens (4/8 primary and 13/26 secondary syphilis), whereas
      immunohistochemical analysis disclosed spirochetes in 29 (8/8 primary and 21/26
      secondary syphilis). In secondary syphilis, an epitheliotropic pattern
      characterized by abundant spirochetes in the lower mucosa/epidermis in an
      intercellular distribution was observed. In contrast, primary syphilis exhibited
      a mixed epitheliotropic and vasculotropic pattern further manifested by
      treponemes surrounding the vascular walls. These differences were statistically
      significant. Ultrastructural examination confirmed these results.
      Immunohistochemistry shows greater sensitivity when compared with Warthin-Starry
      staining. The immunohistochemical pattern of T pallidum distribution may permit
      the diagnostic differentiation of primary from secondary syphilis.

PMID- 19157500
TI  - Increased expression of mucosal addressin cell adhesion molecule 1 in the
      duodenum of patients with active celiac disease is associated with depletion of
      integrin alpha4beta7-positive T cells in blood.
AB  - Mucosal addressin cell adhesion molecule 1, expressed on gut endothelial cells,
      in conjunction with integrin alpha(4)beta(7), expressed on lymphocytes, is
      critical in lymphocyte homing to the gut. The mucosal addressin cell adhesion
      molecule 1/integrin alpha(4)beta(7) pathway is involved in the pathogenesis of
      chronic intestinal inflammation by recruiting lymphocytes into inflamed gut. We
      explored the duodenal expression of mucosal addressin cell adhesion molecule 1
      and the peripheral T-cell expression of integrin alpha(4)beta(7) in patients with
      celiac disease. Duodenal biopsies and a peripheral blood sample were collected
      from 15 celiac patients, before and after 12 months of gluten-free diet, and from
      12 control subjects. Treated celiac biopsies were cultured with peptic-tryptic
      digest of gliadin and/or an anti-interferon alpha neutralizing antibody. Mucosal
      addressin cell adhesion molecule 1 was determined by confocal immunofluorescence
      microscopy and immunoblotting. Integrin beta(7)-positive T cells were analyzed by
      flow cytometry. Mucosal addressin cell adhesion molecule 1 expression was
      significantly higher in active celiac disease than in normal mucosa. After gluten
      free diet, a dramatic reduction of mucosal addressin cell adhesion molecule 1 was
      also observed. No difference was seen between patients with celiac disease after
      treatment and controls. Ex vivo peptic-tryptic digest of gliadin challenge
      induced a marked increase of mucosal addressin cell adhesion molecule 1
      expression. Blocking interferon alpha inhibited the peptic-tryptic digest of
      gliadin-induced mucosal addressin cell adhesion molecule 1 overexpression. The
      percentage of circulating beta(7)-positive T cells was significantly lower in
      untreated celiac disease in comparison to controls but normalized after gluten
      free diet. Mucosal addressin cell adhesion molecule 1 is strongly up-regulated in
      active celiac disease dependent on interferon alpha and is associated with
      peripheral depletion of integrin alpha(4)beta(7)-expressing T cells. We conclude
      that mucosal addressin cell adhesion molecule 1 may represent an important
      determinant for the generation of mucosal damage in celiac disease.

PMID- 19157501
TI  - Pediatric sinonasal neuroendocrine carcinoma after treatment of retinoblastoma.
AB  - Patients who survive retinoblastoma are at risk for developing additional
      malignant neoplasms, including tumors of the sinonasal tract. We report 2 cases
      of secondary sinonasal malignancy arising in pediatric patients previously
      treated for retinoblastoma, with features of neuroendocrine carcinoma. Both
      lesions were characterized by a proliferation of round to oval cells arranged in
      solid sheets, trabeculae, and nests, diffusely infiltrating nasal mucosa and bone
      tissue. Immunohistochemically, they were diffusely positive for epithelial
      markers, as well as for neuroendocrine markers and for TP53 and retinoblastoma
      gene products. TP53 gene analysis showed the presence of a missense mutation P72R
      (CCC/CGC) and a single nucleotide polymorphism P36P (CCG/CCA) in exon 4 in 1
      case. Literature review revealed 5 previously reported cases, all showing
      primitive undifferentiated morphology with variable expression of neural and
      epithelial markers. These tumors represent a peculiar subset of undifferentiated
      sinonasal neoplasms with extremely aggressive clinical behavior.

PMID- 19157502
TI  - Aurora kinases as prognostic biomarkers in ovarian carcinoma.
AB  - We investigated the expression of Aurora kinases A and B by immunohistochemistry
      in 68 ovarian carcinomas to analyze their prognostic value. The amplification of
      AURKA gene by fluorescence in situ hybridization was also assessed. Overall,
      58.8% and 85.3% of ovarian carcinomas showed expression of Aurora A and B,
      respectively. Amplification of AURKA was found in 27.6% of cases examined. Tumors
      with Aurora A expression showed a lower rate of recurrence than those tumors
      without Aurora A expression (65% versus 91.7%, P = .019). In the univariate
      analysis, patients with Aurora A and B expression showed an increased progression
      free survival (P = .023 and .06, respectively, log-rank test) and overall
      survival (P = .03 and .02, respectively, log-rank test). The multivariate
      analysis adjusted to optimal surgery by Cox proportional hazards regression
      showed Aurora A expression as an independent prognostic factor for progression
      free survival (P = .03) and overall survival (P = .02). In conclusion, Aurora A
      expression seems to have a prognostic value in ovarian carcinoma.

PMID- 19157503
TI  - Lymphoepithelial cyst of the parotid gland: its possible histopathogenesis based
      on clinicopathologic analysis of 64 cases.
AB  - Sixty-four cases of lymphoepithelial cysts of the parotid gland, the largest
      scale collection in the literature, were clinicopathologically analyzed for their
      possible pathogenesis. All 64 cases were unilateral, 27 left and 37 right. There
      were 28 male and 36 female patients with a ratio of 1:1.3. The mean age of the
      patients was 52.0 years, and their average duration of symptoms was 29.3 months.
      The mean longest diameter of the cysts was 3.0 cm. Histologically,
      lymphoepithelial cysts were classified into 3 subtypes: type I, a cystic dilation
      of ducts within parotid glands (9 cases, 14.1%); type II, partially demarcated
      cystic lesions with lymphoid stroma (27, 42.2%); type III, well-encapsulated
      cystic lesions with lymphoid stroma containing lymph follicular structures (28,
      43.8%). Based on immunohistochemical results for lymphocyte/macrophage
      (CD20/CD45RO/IgG4), cell cycle (Ki-67), and lymphatic (D2-40) markers, the
      lymphoid stroma was shown to have neither the usual lymph follicular
      distributions of T/B cells nor lymph sinus structures. No viral infection was
      confirmed. The results seemed to indicate that the lymphoid stroma were induced
      along with the growth of the cystic dilatation of ducts within sialadenitis,
      which were neither induced by Epstein-Barr virus nor HIV infections, and that the
      formation of lymphoepithelial cysts was completed by demarcation, which should
      have been a kind of granulation tissue reaction, from the parotid parenchyma but
      did not arise from intraparotid lymph nodes.

PMID- 19157504
TI  - Prognostic value of apoptosis-related markers in urothelial cancer of the upper
      urinary tract.
AB  - We investigated the expression of apoptosis-related markers and their association
      with the clinical outcomes of patients with urothelial carcinoma of the upper
      urinary tract. A total of 112 patients with urothelial carcinoma of the upper
      urinary tract that had surgery from March 1998 to July 2005 were included in the
      study. Tissue microarray slides were used for immunohistochemistry, and
      immunohistochemical staining was performed to investigate the association of
      apoptosis-related markers with clinical outcome. Apoptosis was confirmed by the
      TdT-mediated DUTP nick-end labeling method to obtain the apoptotic index.
      Survival analysis was performed according to the Kaplan-Meier method, and the Cox
      proportional hazard regression model was used to compare the relative influence
      of different prognostic factors. Among the 112 patients, 32 (28.6%) had altered
      expression of p53, 30 (26.8%) of bcl-2, 62 (55.4%) of bax, 27 (24.1%) of caspase
      3, and 23 (20.5%) of survivin. The expression of p53 and caspase-3 was associated
      with the pathologic grade (P = .035 and P = .004, respectively). Altered
      expression of caspase-3 was associated with the pathologic stage (P = .016). The
      multivariate analysis showed that the expression of survivin (hazard ratio 2.91,
      95% confidence interval 1.07-7.90, P = .036) and the apoptotic index (AI) (3.35,
      1.06-10.56, P = .039), as well as the T and N stages (P = .043 and P = .010,
      respectively) were significantly associated with the disease-specific survival.
      Our results suggest that survivin expression and a high apoptotic index were poor
      prognostic factors for survival in patients with urothelial carcinoma of the
      upper urinary tract. These results may help to identify a subset of patients who
      require adjuvant therapy or closer follow-up.

PMID- 19157505
TI  - Diagnostic use of cytokeratins, CD34, and neuronal cell adhesion molecule
      staining in focal nodular hyperplasia and hepatic adenoma.
AB  - Cytokeratins 7 and 19 and neuronal cell adhesion molecule (CD56) are
      differentially expressed in the hepatocytes and biliary epithelium. CD34 is an
      endothelial marker that is expressed in hepatic sinusoids in conditions
      associated with altered vascular flow and neoplasms. Distinct staining patterns
      using these markers have been shown in resected specimens of focal nodular
      hyperplasia, telangiectatic focal nodular hyperplasia, and hepatic adenoma. The
      purpose of this study was to examine the diagnostic use of these markers in
      needle biopsies. Needle biopsies from focal nodular hyperplasia (n = 21),
      telangiectatic focal nodular hyperplasia (n = 2), and hepatic adenoma (n = 14)
      were included in the study. These cases represent typical examples of each entity
      that have been diagnosed on the basis of clinical, imaging, and histologic
      features. Corresponding resection specimens available in 9 cases were also
      included in the study for comparison. Immunohistochemical analysis was performed
      on 4-mum-thick formalin-fixed and paraffin-embedded sections using antibodies
      against cytokeratin 7, cytokeratin 19, neuronal cell adhesion molecule, and CD34.
      The staining patterns and intensity for each marker were analyzed in a blinded
      fashion, and the patterns were recorded as focal nodular hyperplasia-like,
      hepatic adenoma-like, or indeterminate for each case. Presence of normal tissue
      was also recorded in each case. The hepatic adenoma-like pattern is characterized
      by strong cytokeratin 7 positivity in hepatocytes in patches with a gradual
      decrease in the staining intensity as the cells differentiate toward mature
      hepatocytes. Hepatic adenomas lack bile ducts and ductules as highlighted by
      cytokeratin 7, cytokeratin 19, and neuronal cell adhesion molecule stains. The
      focal nodular hyperplasia-like pattern is characterized by milder and focal
      cytokeratin 7 staining of hepatocytes. Cytokeratin 7, cytokeratin 19, and
      neuronal cell adhesion molecule show a strong staining of bile ductules in the
      fibrous septa. Normal liver shows cytokeratin 7, cytokeratin 19, and neuronal
      cell adhesion molecule staining of bile ducts, whereas the hepatocytes are
      generally negative. Of the 21 focal nodular hyperplasia cases, 20 cases (95.2%)
      showed a focal nodular hyperplasia-like pattern, whereas 13 (92.2%) of 14 hepatic
      adenoma cases showed a hepatic adenoma-like pattern. Both cases of telangiectatic
      focal nodular hyperplasia showed a hepatic adenoma-like pattern. CD34 stain
      showed areas of diffuse endothelial staining in 2 cases of hepatic adenoma, 3
      cases of focal nodular hyperplasia, and both cases of telangiectatic focal
      nodular hyperplasia, whereas the remaining cases showed staining of endothelial
      cells only in the inflow areas of the sinusoids. A mixed (diffuse and inflow)
      pattern of CD34 staining was seen in 1 focal nodular hyperplasia, 1 hepatic
      adenoma, and 2 telangiectatic focal nodular hyperplasia cases. For statistical
      analysis, the telangiectatic focal nodular hyperplasia were considered as
      variants of hepatic adenoma. The findings were found to be highly statistically
      significant (P < .05) for cytokeratin 7, cytokeratin 19, and neuronal cell
      adhesion molecule stains. An inflow staining pattern favors a diagnosis of focal
      nodular hyperplasia; however, overall, CD34 stain was not helpful in
      differentiating focal nodular hyperplasia and hepatic adenoma. Corresponding
      resection specimens (hepatic adenoma = 5, focal nodular hyperplasia = 2) showed
      staining patterns that were identical to the biopsy, whereas resections of the
      telangiectatic focal nodular hyperplasia cases showed both focal nodular
      hyperplasia and hepatic adenoma-like areas. Considering that telangiectatic focal
      nodular hyperplasia is now thought to be a variant of hepatic adenoma, the
      staining patterns correctly identified all cases, except one case each of focal
      nodular hyperplasia and hepatic adenoma. In summary, a combination of cytokeratin
      7, cytokeratin 19, and neuronal cell adhesion molecule immunostains performed on
      needle biopsies of liver shows distinctive patterns similar to that of resection
      specimen. The stains, especially cytokeratins 7 and 19, are very helpful in
      distinguishing normal from lesional tissue, as well as hepatic adenoma from focal
      nodular hyperplasia, and could be diagnostically helpful in challenging cases.
      Prospective studies to evaluate use of these stains in challenging cases are
      needed to validate these findings.

PMID- 19157506
TI  - Cleaved caspase-3 and nuclear factor-kappaB p65 are prognostic factors in
      metastatic serous ovarian carcinoma.
AB  - Tumor progression and treatment failure in ovarian carcinoma are frequently
      associated with metastasis to effusions. The present study analyzed the
      expression and clinical role of nuclear factor-kappaB p65, nuclear factor-kappaB
      inhibitor alpha, and parameters of apoptosis in serous carcinoma. Cleaved caspase
      3 and caspase-8 levels and deoxyuridine triphosphate incorporation were measured
      in 65 effusions using flow cytometry. Effusions (n = 209) and corresponding
      primary carcinomas and solid metastases (n = 114) were immunohistochemically
      analyzed for nuclear factor-kappaB p65 and nuclear factor-kappaB inhibitor alpha
      expression. Effusions (n = 75) were further analyzed for nuclear factor-kappaB
      phospho-p65 (Ser536) levels using immunoblotting. Results were analyzed for
      association with anatomic site, clinicopathologic parameters, and survival.
      Caspase cleavage and deoxyuridine triphosphate incorporation were limited to less
      than 10% of cells in most effusions. Nuclear factor-kappaB p65 expression was
      frequently detected at all anatomic sites, with less frequent cytoplasmic nuclear
      factor-kappaB p65 and nuclear factor-kappaB inhibitor alpha expressions.
      Immunoblotting showed nuclear factor-kappaB p65 phosphorylation in 72 (96%) of 75
      effusions. Higher than median cleaved caspase-3 levels correlated with improved
      overall and progression-free survival in univariate analysis of all patients (P =
      .024 and P = .046, respectively) and of those with postchemotherapy effusions (P
      = .042 and P = .036, respectively). Cleaved caspase-3 expression was an
      independent predictor of longer progression-free survival for patients with
      postchemotherapy effusions (P = .029). Nuclear factor-kappaB p65 expression
      correlated with poor progression-free survival for all patients (P = .048) and
      for those with postchemotherapy effusions (P = .025). Ovarian carcinoma cells in
      effusions undergo little apoptosis, but high levels of cleaved caspase-3 are
      associated with improved survival. Nuclear factor-kappaB p65 is frequently
      expressed in advanced-stage serous ovarian carcinoma, and its nuclear
      localization is associated with poor progression-free survival.

PMID- 19157507
TI  - Expression of the peroxisome proliferator-activated receptors-alpha, -beta, and 
      gamma in ovarian carcinoma effusions is associated with poor chemoresponse and
      shorter survival.
AB  - Peroxisome proliferator-activated receptors regulate lipid metabolism, affecting
      inflammation and cancer. The present study analyzed the anatomical site-related
      expression and prognostic role of peroxisome proliferator-activated receptors in
      ovarian carcinoma. Fresh-frozen effusions (n = 79), primary carcinomas (n = 44),
      and solid metastases (n = 16) were studied for peroxisome proliferator-activated
      receptor-alpha, -beta, and -gamma messenger RNA expression using reverse
      transcriptase polymerase chain reaction. Peroxisome proliferator-activated
      receptor-gamma messenger RNA expression was further assessed in 60 tumors (30
      effusions, 20 primary carcinomas, 10 metastases) using in situ hybridization.
      Peroxisome proliferator-activated receptor-gamma protein expression was
      immunohistochemically analyzed in 160 effusions. All peroxisome proliferator
      activated receptors were expressed in most tumors at all anatomical sites using
      reverse transcriptase polymerase chain reaction, but peroxisome proliferator
      activated receptor-alpha (P = .004) and peroxisome proliferator-activated
      receptor-beta (P = .002) messenger RNA levels were higher in effusions compared
      with primary carcinomas and solid metastases. In situ hybridization localized
      peroxisome proliferator-activated receptor-gamma messenger RNA to carcinoma cells
      in both effusions and solid lesions. Peroxisome proliferator-activated receptor
      gamma protein was detected in carcinoma cells in 102 of 160 (64%) effusions.
      Higher effusion messenger RNA levels of all peroxisome proliferator-activated
      receptors were associated with less favorable response to chemotherapy at
      diagnosis (P = .009). In univariate survival analysis, higher messenger RNA
      expression of all peroxisome proliferator-activated receptors was associated with
      poor progression-free (P = .045) and overall (P = .014) survival. Higher
      peroxisome proliferator-activated receptor-gamma protein expression was similarly
      associated with poor overall survival for the entire cohort (P = .046) and for
      patients with disease recurrence effusions (P = .009). Peroxisome proliferator
      activated receptors were not independent predictors of survival in Cox
      multivariate analysis. Peroxisome proliferator-activated receptor members are
      frequently expressed in ovarian carcinoma, with upregulated expression in
      effusions. Peroxisome proliferator-activated receptor expression in effusions is
      associated with poor response to chemotherapy at disease recurrence and poor
      survival, suggesting a role in tumor biology at this unique microenvironment.

PMID- 19157508
TI  - Prognostic significance of paired epithelial cell adhesion molecule and E
      cadherin in ovarian serous carcinoma.
AB  - This study was designed to investigate the prognostic significance of the
      expression of paired epithelial cell adhesion molecule and E-cadherin in ovarian
      serous carcinoma. The expression of epithelial cell adhesion molecule and E
      cadherin was examined immunohistochemically on a tissue microarray of formalin
      fixed paraffin-embedded tissue specimens from 72 consecutive patients. The
      overexpression of epithelial cell adhesion molecule was correlated with poor
      survival (P = .036). In contrast, the reduced expression of E-cadherin was
      correlated with poor survival (P = .034). When patients were subclassified into 4
      groups according to positivity and negativity of epithelial cell adhesion
      molecule and E-cadherin expression, the epithelial cell adhesion molecule
      positive E-cadherin-negative group showed the worst survival rate (P = .002,
      compared with the epithelial cell adhesion molecule-negative E-cadherin-positive
      group). These data suggest that the overexpression of epithelial cell adhesion
      molecule and reduced expression of E-cadherin in combination is more significant
      than a single marker for predicting poor survival.

PMID- 19157509
TI  - Higher temperature and urbanization affect the spatial patterns of dengue fever
      transmission in subtropical Taiwan.
AB  - Our study conducted spatial analysis to examine how temperature and other
      environmental factors might affect dengue fever distributions, and to forecast
      areas with potential risk for dengue fever endemics with predicted climatic
      change in Taiwan. Geographic information system (GIS) was used to demonstrate the
      spatial patterns of all studied variables across 356 townships. Relationships
      between cumulative incidence of dengue fever, climatic and non-climatic factors
      were explored. Numbers of months with average temperature higher than 18 degrees
      C per year and degree of urbanization were found to be associated with increasing
      risk of dengue fever incidence at township level. With every 1 degrees C increase
      of monthly average temperature, the total population at risk for dengue fever
      transmission would increase by 1.95 times (from 3,966,173 to 7,748,267). A highly
      suggested warmer trend, with a statistical model, across the Taiwan Island is
      predicted to result in a sizable increase in population and geographical areas at
      higher risk for dengue fever epidemics.

PMID- 19157510
TI  - Sensitivity to UV radiation in early life stages of the Mediterranean sea urchin
      Sphaerechinus granularis (Lamarck).
AB  - The sea urchin Sphaerechinus granularis was used to investigate the impact of
      relevant levels of UV-B radiation on the early life stages of a common
      Mediterranean free spawning benthic species. Sperm, eggs and embryos were exposed
      to a range of UV radiation doses. The resulting endpoints were evaluated in terms
      of fertilisation success, development and survival rates. Above a weighted UV
      radiation dose of 0.0029 kJ m(-2), fertilisation capability of irradiated sperm
      decreased rapidly. The exposure of the eggs to 0.0175 kJ m(-2) and more led to
      delayed and inhibited development with ensuing embryonic morphological
      abnormalities. One-day old larvae remained strongly sensitive to UV radiation as
      shown by the 50% decrease of the larval survival rate for a dose of 0.025 kJ m(
      2) UVR. The elevated sensitivity of embryos to experimental UVR went along with a
      lack of significant amount of sunscreen compounds (e.g., mycosporine-like amino
      acids) in the eggs. The present results demonstrated that gamete viability and
      embryonic development may be significantly impaired by solar UV radiation in S.
      granularis, compromising in this way the reproduction of the species. Unless
      adaptive behavioural reproductive strategies exist, the influence of ambient UV
      radiation appears as a selective force for population dynamics of broadcast
      spawners in the shallow benthic Mediterranean environment.

PMID- 19157511
TI  - An environmental record of changes in sedimentary organic matter from Lake Sattal
      in Kumaun Himalayas, India.
AB  - Sattal a small mountainous lake in the Kumaun Himalayas has been impacted by
      various cultural activities in recent years. We explored the effects of human
      induced changes in this lake by using various geochemical proxies. Shifts in TOC
      and N flux, C/N ratio, stable isotopes (delta13C and delta(15)N), n-alkane, and
      pigment concentrations in sediments indicate a steady increase in primary
      productivity over the last few decades. The trophic status of the lake has
      changed from mesotrophic to eutrophic condition. The C/N, CPI, and TAR based
      ratios in sediments indicate accumulation of algal matter derived primarily from
      in situ production, with limited input of terrestrial organic matter from the
      watershed. The low (between 0.1 and 1 per thousand) delta15N values imply N2
      fixation by cyanobacteria, and the decrease in delta13C values up-core represent
      the effect of sewage input and land based runoff, or possible contribution from
      microbial biomass. The pigments change from non-N2 fixing cyanobacterial species
      to the N2-fixing community, and are consistent with the proxy-based productivity
      shifts inferred in the lake. The deeper sediments are affected by post-diagenetic
      changes causing an increase in delta13C (and possibly delta15N) due to
      mineralization of organic C and N.

PMID- 19157512
TI  - Effect of temperature on carbon nanoparticle collection efficiency using
      photoelectric ESP.
AB  - The electrostatic precipitator (ESP) technique is a promising method for
      enhancing the particulate matter (PM) emission reduction efficiency of diesel
      engines, and is much better than the diesel particulate filter (DPF) technique.
      However, the ESP's low efficiency in collecting PM with diameters less than
      several tens of nanometers remains a problem because the particle charging
      efficiency decreases as the size of the nanoparticles decreases. To improve the
      collection efficiency of nanosized PM, we used a photoelectric charger to
      increase the charging efficiency of nanoparticles ahead of the ESP system. Carbon
      nanoparticles produced using a spark discharge generator were used to evaluate
      the collection efficiency of the combined photoelectric charger and ESP system.
      The particle sizes were measured using a scanning mobility particle sizer system
      at various experimental temperatures similar to the temperature of DPF systems
      commonly used in diesel engines. We succeeded in obtaining improved collection
      efficiencies at increased inner temperatures of the photoelectric charging
      chamber. As the temperature increased from 694 degrees C to 839 degrees C at the
      inlet of the photoelectric chamber, the efficiency of PM collection improved
      significantly to 28.5% for a particle diameter of 18.4 nm.

PMID- 19157513
TI  - The effect of uric acid on outdoor copper and bronze.
AB  - Bird droppings are often quoted as a decay agent for outdoor goods, in particular
      buildings and statues. Undoubtedly, they represent one of the major causes of
      aesthetic damage on outdoor materials, but the real chemical damage they are able
      to induce, in particular on metals, is not so well studied. This work focused on
      the short term role of uric acid, the main constituent of bird urine, with
      respect to copper, which make such an important contribution to architectural
      elements of buildings and outdoor sculpture. Preliminary results of laboratory
      tests and analyses on real exposed samples showed that uric acid chemically
      affects copper and bronzes: the surface of the metal is modified and copper
      urates formed. Also natural patina, formed on statues and roof, react with uric
      acid, even if it seems to afford some protection toward bird droppings. In
      general, experimental results confirm that the potential chemical damage by bird
      droppings is significant when considering external cultural heritage such as
      statues, metal monuments and buildings with historic copper roofs.

PMID- 19157514
TI  - Accumulation and in vivo tissue distribution of pollutant elements in Erica
      andevalensis.
AB  - Erica andevalensis is an endemic shrub from an area in the southwest of Spain
      (Andalucia) characterized by acidic and contaminated soils. Scanning electron
      microscopy (SEM) of samples after conventional or cryo-fixation preparation
      protocols was used for morphological and anatomical studies. SEM coupled with EDX
      analysis was employed to localise and quantify different elements within plant
      parts (leaves, stems and roots) in samples collected in the field. Morphological
      studies revealed that the species has typical adaptive structures to drought
      stress such as rolled needle-like leaves, sunken stomata and a thick waxy cuticle
      on the upper epidermis. Roots were associated with fungi which formed intra and
      extra-cellular mycelia. The SEM studies showed that Cu was not sequestrated into
      the root tissues and was uniformly distributed in leaf tissues. Meanwhile, Pb was
      only localised within epidermal root tissues which indicates that its
      sequestration in an external matrix might represent a tolerance mechanism in this
      species. Iron was uniformly distributed throughout the leaves, while in roots it
      was predominantly retained on the epidermal cell walls. The exclusion and
      tolerance mechanisms adopted by this species to survive in mining areas indicate
      that it can be used successfully in the re-vegetation of contaminated areas.

PMID- 19157516
TI  - Understanding the physical processes of pollutant build-up and wash-off on roof
      surfaces.
AB  - Pollutants originating with roof runoff can have a significant impact on urban
      stormwater quality. This signifies the importance of understanding pollutant
      processes on roof surfaces. Additionally, knowledge of pollutant processes on
      roof surfaces is important as roofs are used as the primary catchment surface for
      domestic rainwater harvesting. In recent years, rainwater harvesting has become
      one of the primary sustainable water management techniques to counteract the
      growing demand for potable water. This paper presents the outcomes of an in-depth
      research study into particulate matter build-up and wash-off for roof surfaces.
      In this research, particulate matter was considered as the indicator pollutant
      where the processes related to other pollutants can be predicted based on the
      understanding generated for particulate matter. The study outcomes confirm that
      the build-up process on roof surfaces is comparatively similar to road surfaces.
      However, particle loads collected from roofs were significantly less compared to
      road surfaces and much finer in texture. Wash-off from roofs also showed
      significant similarities to wash-off from roads. A relatively high concentration
      of particulate matter was noted during the initial part of storm events.
      Furthermore, the amount of particulate matter remaining on the roof surfaces was
      significantly high for less intense rain events.

PMID- 19157515
TI  - Antibiotic resistant enterococci and staphylococci isolated from flies collected
      near confined poultry feeding operations.
AB  - Use of antibiotics as feed additives in poultry production has been linked to the
      presence of antibiotic resistant bacteria in farm workers, consumer poultry
      products and the environs of confined poultry operations. There are concerns that
      these resistant bacteria may be transferred to communities near these operations;
      however, environmental pathways of exposure are not well documented. We assessed
      the prevalence of antibiotic resistant enterococci and staphylococci in stored
      poultry litter and flies collected near broiler chicken houses. Drug resistant
      enterococci and staphylococci were isolated from flies caught near confined
      poultry feeding operations in the summer of 2006. Susceptibility testing was
      conducted on isolates using antibiotics selected on the basis of their importance
      to human medicine and use in poultry production. Resistant isolates were then
      screened for genetic determinants of antibiotic resistance. A total of 142
      enterococcal isolates and 144 staphylococcal isolates from both fly and poultry
      litter samples were identified. Resistance genes erm(B), erm(A), msr(C), msr(A/B)
      and mobile genetic elements associated with the conjugative transposon Tn916,
      were found in isolates recovered from both poultry litter and flies. Erm(B) was
      the most common resistance gene in enterococci, while erm(A) was the most common
      in staphylococci. We report that flies collected near broiler poultry operations
      may be involved in the spread of drug resistant bacteria from these operations
      and may increase the potential for human exposure to drug resistant bacteria.

PMID- 19157517
TI  - Microbial biomass, activity and community composition in constructed wetlands.
AB  - The aim of the current article is to give an overview about microbial communities
      and their functioning but also about factors affecting microbial activity in the
      three most common types (surface flow and two types of sub-surface flow) of
      constructed wetlands. The paper reviews the community composition and structural
      diversity of the microbial biomass, analyzing different aspects of microbial
      activity with respect to wastewater properties, specific wetland type, and
      environmental parameters. A brief introduction about the application of different
      novel molecular techniques for the assessment of microbial communities in
      constructed wetlands is also given. Microbially mediated processes in constructed
      wetlands are mainly dependent on hydraulic conditions, wastewater properties,
      including substrate and nutrient quality and availability, filter material or
      soil type, plants, and different environmental factors. Microbial biomass is
      within similar ranges in both horizontal and vertical subsurface flow and surface
      flow constructed wetlands. Stratification of the biomass but also a stratified
      structural pattern of the bacterial community can be seen in subsurface flow
      systems. Microbial biomass C/N ratio is higher in horizontal flow systems
      compared to vertical flow systems, indicating the structural differences in
      microbial communities between those two constructed wetland types. The total
      activity of the microbial community is in the same range, but heterotrophic
      growth is higher in the subsurface (vertical flow) system compared to the surface
      flow systems. Available species-specific data about microbial communities in
      different types of wetlands is scarce and therefore it is impossible make any
      general conclusions about the dynamics of microbial community structure in
      wetlands, its relationship to removal processes and operational parameters.

PMID- 19157518
TI  - The isotopic record of atmospheric lead fall-out on an Icelandic salt marsh since
      AD 50.
AB  - We report a record of atmospheric Pb deposition at a coastal site in western
      Iceland that spans the last two millennia. The elemental concentrations of Pb,
      Al, Li and Ti are determined using ICP-MS from a sediment monolith collected from
      a salt marsh. Multicollector (MC) ICP-MS analysis is used to obtain isotopic
      ratios of stable Pb. The Pb/Ti and Pb/Li ratios are used to separate natural Pb
      background concentrations from Pb derived from remote anthropogenic sources. The
      pollution record in western Iceland is subdued in comparison with Pb records from
      the European mainland, but the isotopic character, profile and timing of Pb
      deposition show good agreement with the atmospheric Pb fall-out reported from
      sites in Scandinavia and northwestern Europe. At the bottom of the sequence we
      isolate a low-level (0.1-0.4 mg kg(-1)) Pb enrichment signal dated to AD 50-150.
      The isotopic signature and timing of this signal suggest Roman metal working
      industries as the source. In the subsequent millennium there was no significant
      or very low (i.e. elemental concentrations<0.01 mg kg(-1)) anthropogenic Pb
      deposition at the site up to, and including, the early Medieval period. Above a
      pumice layer, dated to AD 1226-1227, a small increase in Pb deposition is found.
      This trend is maintained until a more substantive and progressive increase is
      signalled during the late 1700s and early 1800s. This is followed by a
      substantial enrichment signal in the sediments (>3.0 mg kg(-1)) that is
      interpreted as derived from industrial coal burning and metal working during the
      19th and 20th centuries in northern Europe. During the late 20th century,
      significant fall-out from European fuel additives reached Iceland.

PMID- 19157519
TI  - Assessing the effects of fluoxetine on Physa acuta (Gastropoda, Pulmonata) and
      Chironomus riparius (Insecta, Diptera) using a two-species water-sediment test.
AB  - Fluoxetine has been tested in a two-species water-sediment system, which allowed
      a two-generation study with Chironomus riparius and a partial life-cycle with the
      freshwater snail Physa acuta to be performed at the same time. The design
      considered the continuous application of fluoxetine to overlaying water for
      nominal concentrations of 31.25, 62.5, 125 and 250 microg/L. A fifth treatment
      (87.5 microg/L) level consisted of pulse applications once a week. Measures of
      water and sediment concentrations were determined once a week and at the end of
      experiment (day 44), respectively. The fate study demonstrated that water
      dissipation can be explained by partitioning of fluoxetine to sediment. At the
      end of experiment, the percentage of detected fluoxetine was up to 10-fold higher
      in sediment than in overlaying water. The employed two-species test allowed
      distinguishing, in the same exposure conditions, effects due to waterborne
      exposure together ingestion at the sediment surface (freshwater grazing snail P.
      acuta) and exposure by burrowing activities (sediment-dwelling insect larvae C.
      riparius). The effect assessment showed a stimulation of P. acuta reproduction at
      lower concentrations (31.25 and 62.5 microg/L), while the opposite effect was
      observed at the highest treatment (250 microg/L). Additional studies should be
      conducted to establish if the statistically significant differences observed in
      F0 sex ratio at the 62.5 microg/L and F1 adult emergence at 31.25 microg/L of C.
      riparius have a toxicological significance. This study showed that fluoxetine can
      affect reproduction of freshwater molluscs. The results of the present study may
      contribute to knowledge on ecotoxicology of pharmaceuticals, about which little
      data is available. The possible consequences and implications for targeting the
      environmental risk assessment of fluoxetine are discussed.

PMID- 19157520
TI  - Forecasting of ozone episode days by cost-sensitive neural network methods.
AB  - Forecasting the occurrence of ozone episode days can be regarded as an imbalanced
      dataset classification problem. Since the standard artificial neural network
      (ANN) methods cannot make accurate predictions of such a problem, two cost
      sensitive ANN methods, cost-penalty and moving threshold, were used in this
      study. The models classify each day as episode or non-episode according to the
      standard of daily maximum 8 h O(3) concentration. The ozone measurements from six
      monitoring stations in Taiwan were used for model training and performance
      evaluation. Two different input datasets, regional and single-site, were
      generated from raw air quality and meteorological observations. According to the
      numerical experiments, the predictions based on the regional dataset are much
      better than those obtained from the single-site dataset. Two cost-sensitive ANN
      methods were evaluated by receiver operating characteristic (ROC) curves. It was
      found that the results obtained by the two approaches are similar. If the
      misclassification costs are known, the cost-sensitive method can minimise the
      total costs. If the misclassification costs are unknown, the cost-sensitive ANN
      can obtain a better forecast than the standard ANN method when an appropriate
      cost ratio is used. For clean areas where episode days are very rare, the
      forecasts are poor for all methods.

PMID- 19157521
TI  - Relationship between winter temperature and mortality in Seoul, South Korea, from
      1994 to 2006.
AB  - In South Korea, the mortality increases with temperature above a certain
      threshold during the warm season. In contrast, despite the common burden of cold
      weather, little is known about the effects of low temperatures on mortality. We
      evaluated the relationship between low temperatures and mortality in winter
      (December-February) in Seoul, South Korea, from 1994 to 2006. Data were obtained
      from government agencies. After adjusting for trends in time, day of the week,
      holidays, and relative humidity, we explored the associations between mortality
      and various cold indicators of winter in Seoul, South Korea. First, we fitted
      nonparametric smoothing regression models to check the shape of associations and
      then fitted threshold models (including two different slopes in a model) to
      estimate the thresholds and the effects of low temperatures using the Akaike
      Information Criterion (AIC). The graphical associations between
      cardiorespiratory, cardiovascular, and all causes of mortality and the cold wave
      index (CWI=T(min, previous day)-T(min, current day)) were observed. We confirmed
      the threshold according to a lag structure and after that, estimated the effects
      of CWI below the threshold, respectively. The effects of the daytime CWI lagged
      by 0-2 days were the strongest among those of the daytime CWI lagged by 0-6 days.
      The most significant mortality outcomes were cardiovascular-related. Although we
      could not consider respiratory-related mortality, the effect of CWI on
      cardiovascular-related mortality below a certain threshold was greater than
      cardiorespiratory-related or all cause-related mortality. In addition, the
      association between mortality and CWI was more immediate and vulnerable in an
      elderly subgroup (> or =65 years old) than in a younger subgroup (0-64 years
      old). Our results suggest that public health programs should be considered to
      alleviate not only the effect of sudden change in winter temperature on
      mortality.

PMID- 19157522
TI  - Exposure to toxic agents alters organic elemental composition in human
      fingernails.
AB  - BACKGROUND AND OBJECTIVE: The human fingernail plate is highly keratinized. The
      keratin structure is held together by disulfide bonds. The organic elements
      sulfur and nitrogen occur almost exclusively in amino acids of the nail plate.
      This study analyzed whether occupational exposure to harmful chemical agents
      alters the organic elemental composition in fingernails. SUBJECTS AND METHODS:
      Participants were 71 occupationally exposed workers (49 hairdressers, 22
      painters) and 49 unexposed controls. Aspects of exposure were assessed by
      questionnaire. Nail clippings of index and little fingers were analyzed for
      sulfur (S), nitrogen (N), carbon (C), and hydrogen (H) contents, using an
      automatic elemental analyzer (Vario EL III, Elementar Analysensysteme, Hanau,
      Germany). C/N, N/S, and C/S ratios were calculated. Reliability of elemental
      measurements was tested in a subset. RESULTS: Reliability analysis of elemental
      measurements showed a very good agreement. Both painters and hairdressers
      displayed in their fingernails significantly lower percentages of sulfur, but
      higher percentages of carbon than unexposed controls. A trend was observed in
      that sulfur content was lowest in those hairdressers who reported structural
      changes in their fingernails. As a consequence, the C/S and N/S ratios were
      significantly increased in both exposed groups. CONCLUSION: The occupational use
      of harmful substances leads to decreased sulfur levels in the exposed persons,
      probably due to diminution of sulfur-rich proteins in the nails, resulting from
      destruction of disulfide-bonds by alkaline and acid groups. Thus, the C/S ratio
      seems to be a useful indicator for the amount of damage of nail protein by
      harmful agents.

PMID- 19157523
TI  - Occurrence and removal of pharmaceuticals in a municipal sewage treatment system
      in the south of Sweden.
AB  - The occurrence and removal rate of seven pharmaceuticals (ibuprofen, naproxen,
      diclofenac, fluoxetine, ofloxacin, norfloxacin, ciprofloxacin), two metabolites
      (norfluoxetine, clofibric acid), one degradation product (4-isobutylacetophenone)
      and 3 estrogens (17alpha-ethinylestradiol, 17beta-estradiol, estrone) were
      studied in the inlet and outlet of a tertiary sewage treatment plant (STP) in
      Sweden as well as between different treatment steps in the STP which includes a
      conventional activated sludge step. Pharmaceuticals in raw household and raw
      hospital sewage streams leading to the STP were as well investigated. Hydraulic
      retention times (HRT) of each treatment step was considered for sampling and for
      the calculation of the removal rates. These rates were above 90%, except for
      diclofenac, clofibric acid, estrone and ofloxacin. However, only diclofenac and
      naproxen showed significant effluent loads (>145 mg/d/1000 inh). Diclofenac was
      not eliminated during the treatment and in fact even higher concentrations were
      found at the effluent than in the inlet of the STP. 17alpha-Ethinylestradiol was
      not detected in any of the samples. Results indicate that a STP such as the one
      in Kristianstad, Sweden, with a tertiary treatment is sufficient to remove
      significantly most of the investigated pharmaceuticals. The chemical treatment
      improved the removal of several pharmaceuticals especially the antibiotics, which
      showed step removal rates between 55 and 70%. The expected concentration levels
      of the pharmaceuticals in the surface water (dilution 1 to 10) close to the
      outlet of the STP are below the no-observed effect-concentration (NOEC). However,
      despite that this would imply no important effects in the aquatic environment one
      cannot rule out negative consequences nearby the STP because most of the NOEC
      values are derived from acute toxicity data. This may underestimate the real
      impact of pharmaceuticals in the aquatic ecosystem.

PMID- 19157524
TI  - A new chromogenic assay (HemosIL ThromboPath) is sensitive to major prothrombotic
      risk factors affecting the protein C pathway. Results of a multicenter study.
AB  - The HemosIL ThromboPath assay (Instrumentation Laboratory) is a new chromogenic
      assay designed to globally evaluate the functionality of the protein C (PC)
      pathway. It is based on the ability of endogenous APC generated after activation
      of PC by a snake venom extract (Protac) to reduce the thrombin generation induced
      by a reagent containing tissue factor. The aim of this multicenter study
      involving three laboratories was to evaluate the test sensitivity to PC pathway
      abnormalities by retrospectively testing frozen plasma samples obtained in the
      different laboratories. Test results were significantly lower (p < 0.0001) in
      subjects who presented with any confirmed PC pathway abnormality than in those
      without. The cut-off value, defined in each participating center as the mean
      value minus one standard deviation of test results obtained in 30 normal samples,
      was found to provide a sensitivity-to-specificity ratio similar to that obtained
      using ROC-analysis. The assay performed well in carriers of the factor V Leiden
      mutation (n = 81), patients with PC deficiency (n = 40), combined defects (n =
      55) or lupus anticoagulant (n = 44), with test results below the locally defined
      cut-off values in 97.5%, 95.0%, 100% and 100% of the tested subjects,
      respectively. The assay sensitivity for PS deficiency (n = 62) was 87.1%. Only
      13.6% of the 272 subjects without any PC pathway abnormality had a decreased test
      result. So, using the locally defined cut-off values, the overall test
      sensitivity to all tested PC pathway abnormalities was 95.0% (95%CI = 91.8-97.3),
      its specificity 86.4% (95%CI = 81.8-90.2), its negative predictive value 94.4%
      (95%CI = 90.8-96.9) and its positive predictive value 87.9% (95%CI = 83.7-91.3).

PMID- 19157525
TI  - The relevance of the aldehyde bisulfite toluidine blue reaction and its variants
      in the submicroscopic carbohydrate research.
AB  - Carbohydrates are chemical compounds that contain only oxygen, hydrogen and
      carbon. They are classified by their number of sugar units: monosaccharides (such
      as glucose and fructose), and disaccharides (such as sucrose and lactose) are
      simple carbohydrates; oligosaccharides and polysaccharides (such as starch,
      glycogen and cellulose) are complex carbohydrates. Carbohydrates play a crucial
      role in diverse biological systems [Hricovin M. Structural aspects of
      carbohydrates and the relation with their biological properties. Curr Med Chem
      2004;11:2565-83]. According to Roseman [Sugars of the cell membrane. In:
      Weissmann G, Clairborn E, editors. Cell membranes. Biochemistry, Cell Biology,
      Pathology. New York: H. P. Publ. Co; 1975. p. 55-64], two classes of
      glycoproteins are described. Free glycoproteins are localised in the surface coat
      of the membranes and form a thick mobile layer, without any association to the
      membrane itself. Functionally, however, they are located in a close association
      with the membrane (e.g. in the duodenal mucosa). The other group consists of the
      membrane glycoproteins, which are integral to the membranes and are located in
      the outer layer. The oligosaccharide chains are bound to the N-terminal part of
      proteins, and are situated in the hydrophilic zone. Glycoproteins have diverse
      functions. They are important in specific receptor functions, in immunological
      cell destruction and play a significant role in reactions with lectins,
      antibodies, as well as in cell association and mutual recognition of the cells.
      This paper focuses on aspects of a summary of polarisation optical investigations
      and biological functions of the following three groups of carbohydrates:
      oligosaccharides, glycoproteins and glycosaminoglycans.

PMID- 19157526
TI  - Pelvic and aortic lymphadenectomy in cervical cancer: the standardization of
      surgical procedure and its clinical impact.
AB  - Cervical cancer ranks as the second most frequent cancer in women in the world,
      and nodal metastasis seems to be the first step of tumor spread in most cases.
      Since lymph node involvement is a major prognostic factor in cervical carcinoma,
      lymphatic spread of cervical cancer has been one of the most studied surgical
      topics in gynecologic oncology. Traditionally, lymph nodes stations have been
      accurately analyzed, improving surgical techniques of nodal dissection, which
      have been more and more intensive during years with the aim of improving
      survival. Oppositely, on the basis of recent acquisitions in cancer immunology
      and new anti-cancer immunotherapies and vaccines, the importance of lymph nodes
      has been recently reconsidered. Unfortunately, lymph node status is still
      difficult to be assessed pre-operatively with a high level of accuracy, and intra
      operatively by sentinel node techniques, which remain inadequate for many aspects
      according to several gynecologic oncologists. The absence of definitive evidence
      of survival advantage given by extensive lymphadenectomy in all cervical cancer
      cases indicates that nodal dissection should be performed on the objective risk
      of node metastasis in each case. To date, the mainstay of detecting lymph node
      metastasis is still the histologic evaluation, therefore a proper resection of
      mostly involved lymph nodes remains a crucial surgical step when treating
      cervical cancer.

PMID- 19157527
TI  - Robotic extraperitoneal aortic lymphadenectomy: Development of a technique.
AB  - OBJECTIVES: To develop a robotic technique for extraperitoneal aortic
      lymphadenectomy in cadavers followed by application in a patient with advanced
      cervical cancer. METHODS: Two fresh frozen female torso cadavers were used to
      develop the correct placement of the robotic column and trocars, respectively, to
      allow for a safe and adequate performance of aortic lymphadenectomy using the da
      Vinci S system. The resulting technique was applied to a patient with cervical
      cancer Stage IB2 presenting with enlarged aortic nodes. RESULTS: Appropriate
      sites for trocar and robotic column placement were identified in the female
      cadavers. In the patient, the operating, docking, and console times were 103,
      3.5, and 49 minutes, respectively. The blood loss was 30 ml. Selective removal of
      5 enlarged aortic nodes revealed no evidence of metastases. CONCLUSION: Robotic
      extraperitoneal aortic lymphadenectomy is feasible provided there is proper
      robotic trocar and column placement. The operating time and number of aortic
      nodes selectively removed by robotics in this patient are within the range of
      those reported with an extraperitoneal systematic aortic lymphadenectomy by
      laparoscopy.

PMID- 19157528
TI  - Identification of human papillomavirus type 16 integration sites in high-grade
      precancerous cervical lesions.
AB  - OBJECTIVES: Infection with oncogenic human papillomaviruses (HPV) is a
      prerequisite for the development of cervical cancer. In many cases of cervical
      cancer and all cervical cancer derived cell lines oncogenic HPV DNA is found to
      be integrated, indicating the importance of integration in disease development.
      In this study, 176 HPV 16 positive precancerous cervical lesions were analyzed
      for the physical state of viral genome to determine the sites of integration into
      a host cell DNA and to evaluate the incidence of the integration in different
      stages of cervical lesions. METHODS: The detection of integrated papillomavirus
      sequences (DIPS) method in combination with the amplification by polymerase chain
      reaction (PCR) of E1/E2 region was used to identify the physical state of HPV 16
      genome. The site of integration within a host cell genome was determined by
      sequencing of unusual sized DIPS amplicons. RESULTS: The combined results of DIPS
      and E1/E2 PCR revealed the integration of HPV 16 DNA in 7.4% samples. The
      integration was found only in high grade cervical lesions indicating that it is a
      late event in disease progression. Sequencing of 11 DIPS amplicons revealed HPV
      DNA from 6 samples (54.5%) to be integrated in cellular genes (VMP1, PVRL1,
      CHERP, CEACAM5, AHR, MRF-2) and also 6 (54.5%) within the common fragile sites
      (CFS). CONCLUSIONS: Although, the HPV integration is known to be a random event,
      this study indicates that HPV 16 integrates more than by chance within or close
      to CFSs. As most of the genes affected by HPV 16 integration can be linked with
      some aspects of tumor formation, this indicates that the site of HPV DNA
      integration might play a role in the rate and the nature of tumor development.

PMID- 19157529
TI  - Tyrosine kinase A, C and fibroblast growth factor-2 receptors in bovine embryos
      cultured in vitro.
AB  - Neurotrophins and basic fibroblast growth factor are ligands of tyrosine kinase
      receptors, though they bind to different tyrosine kinase receptor classes.
      Neurotrophins bind to receptor tyrosine kinase class VII, Trk receptor family,
      while basic fibroblast growth factor binds to receptor tyrosine kinase class IV,
      FGF receptor family. The mammalian uterine tract immunolocalizes neurotrophins
      and bFGF; therefore their cognate receptors might exert a role during embryonic
      development. Using RT-PCR, we found mRNA for p75(NTR) TrkA, TrkC and FGFr2
      throughout the early bovine embryonic development in vitro. Immunofluorescent
      staining, assessed by confocal microscopy, showed the expression of TrkA and TrkC
      proteins in oocytes and all embryonic stages analyzed. We have provided a novel
      description of TrkA and TrkC proteins, and TrkA, TrkC, p75(NTR) and FGFr2 mRNA
      expression throughout mammalian embryonic development. This work may help to
      design future research with neurotrophins in bovine embryo culture and embryonic
      stem cells.

PMID- 19157530
TI  - Effect of addition of hyaluronan to embryo culture medium on survival of bovine
      embryos in vitro following vitrification and establishment of pregnancy after
      transfer to recipients.
AB  - Two experiments were conducted to determine whether addition of hyaluronan to
      culture medium could improve survival of bovine embryos after vitrification or
      following embryo transfer. In Experiment 1, embryos were produced in vitro and
      cultured for 7 days in modified synthetic oviductal fluid (SOF) containing one of
      four concentrations of hyaluronan (0, 0.1, 0.5, or 1mg/mL), with or without 4
      mg/mL of bovine serum albumin (BSA). On Day 7 after insemination, blastocysts and
      expanded blastocysts were vitrified using open-pulled straws. At a concentration
      of 1mg/mL, hyaluronan increased (P<0.05) the percentage of oocytes that were
      blastocysts and re-expansion rate at 24h after warming. At 0.5mg/mL, hyaluronan
      tended (P<0.10) to increase re-expansion rate at 48 h after warming and increased
      (P<0.05) embryo hatching rate at 24 and 72 h. Treatment with BSA caused a slight
      reduction in cleavage rate (P<0.05), but only for cultures containing hyaluronan
      (BSAxhyaluronan, P=0.10), an increase in the percentage of oocytes that became
      blastocysts (P<0.001), and a reduction in re-expansion rates (P<0.001) and
      hatching rates (P<0.05 or P<0.01) at all times examined. In Experiment 2, embryos
      were produced in vitro and cultured in modified SOF containing 4 mg/mL BSA, with
      or without 1mg/mL hyaluronan. At 159-162 h after insemination, grade 1 morula,
      blastocysts and expanded blastocysts were harvested for embryo transfer.
      Harvested embryos were transferred individually to lactating Holstein recipients
      with a palpable corpus luteum on Day 7 after presumptive ovulation. There was an
      interaction (P<0.05) between hyaluronan and embryo stage on pregnancy rate.
      Recipients that received morula and blastocyst stage embryos treated with
      hyaluronan had a higher pregnancy rate than recipients that received control
      embryos of the same stage. There was no effect of hyaluronan on pregnancy rates
      of recipients that received expanded blastocysts. In conclusion, addition of
      hyaluronan to embryo culture enhanced blastocyst yield, improved survival
      following vitrification, and enhanced the post-transfer survival of fresh morula
      and blastocyst stage embryos.

PMID- 19157531
TI  - Global and physical self-esteem and body dissatisfaction as mediators of the
      relationship between weight status and being a victim of bullying.
AB  - Research has found evidence of a link between being overweight or obese and
      bullying/peer victimisation, and also between obesity and adjustment problems
      such as low self-esteem and body dissatisfaction. Studies have also found that
      adjustment problems can put children at an increased risk of being bullied over
      time. However, to date the factors that place overweight or obese children at
      risk of being bullied have been poorly elucidated. Self-report data were
      collected from a sample of 11-14 year olds (N=376) about their weight status,
      about their experiences of three different types of bullying (Verbal, Physical
      and Social), their global self-worth, self-esteem for physical appearance, and
      body dissatisfaction. Overweight or obese children reported experiencing
      significantly more verbal and physical (but not social) bullying than their non
      overweight peers. Global self-worth, self-esteem for physical appearance and body
      dissatisfaction each fully mediated the paths between weight status and being a
      victim of bullying.

PMID- 19157532
TI  - Rheumatoid arthritis.
AB  - Rheumatoid arthritis is a systemic, inflammatory, autoimmune disorder. Enhanced
      understanding of molecular pathogenesis has enabled development of innovative
      biological agents that target specific parts of the immune system. These
      treatments have changed the course and face of rheumatoid arthritis and outcomes
      for patients and society. New knowledge has emerged of how environmental factors
      interact with susceptibility genes and the immune system in the pathogenesis of a
      major subset of rheumatoid arthritis. Research undertaken on the longitudinal
      disease process and molecular pathology of joint inflammation has led to new
      therapeutic strategies that promote early use of disease-modifying drugs with
      tight disease control and distinct and quantifiable treatment goals. Today, such
      approaches can halt most cases of joint destruction but not all instances of
      joint inflammation and comorbidity. Understanding the cause and pathogenesis of
      different rheumatoid arthritis subsets will lead not only to individualised
      treatments during early phases of the illness but also, possibly, to disease
      prevention.

PMID- 19157533
TI  - Microporous silk fibroin scaffolds embedding PLGA microparticles for controlled
      growth factor delivery in tissue engineering.
AB  - The development of prototype scaffolds for either direct implantation or tissue
      engineering purposes and featuring spatiotemporal control of growth factor
      release is highly desirable. Silk fibroin (SF) scaffolds with interconnective
      pores, carrying embedded microparticles that were loaded with insulin-like growth
      factor I (IGF-I), were prepared by a porogen leaching protocol. Treatments with
      methanol or water vapor induced water insolubility of SF based on an increase in
      beta-sheet content as analyzed by FTIR. Pore interconnectivity was demonstrated
      by SEM. Porosities were in the range of 70-90%, depending on the treatment
      applied, and were better preserved when methanol or water vapor treatments were
      prior to porogen leaching. IGF-I was encapsulated into two different types of
      poly(lactide-co-glycolide) microparticles (PLGA MP) using uncapped PLGA (50:50)
      with molecular weights of either 14 or 35 kDa to control IGF-I release kinetics
      from the SF scaffold. Embedded PLGA MP were located in the walls or intersections
      of the SF scaffold. Embedment of the PLGA MP into the scaffolds led to more
      sustained release rates as compared to the free PLGA MP, whereas the hydrolytic
      degradation of the two PLGA MP types was not affected. The PLGA types used had
      distinct effects on IGF-I release kinetics. Particularly the supernatants of the
      lower molecular weight PLGA formulations turned out to release bioactive IGF-I.
      Our studies justify future investigations of the developed constructs for tissue
      engineering applications.

PMID- 19157534
TI  - The use of electron beam lithographic graft-polymerization on thermoresponsive
      polymers for regulating the directionality of cell attachment and detachment.
AB  - A simple process for nano-patterned cell culture substrates by direct graft
      polymerization has been developed using an electron beam (EB) lithography system
      requiring no photo-masks or EB-sensitive resists. The compound N
      isopropylacrylamide (IPAAm) was locally polymerized and grafted directly by EB
      lithographic exposure onto hydrophilic polyacrylamide (PAAm)-grafted glass
      surfaces. The size of the surface grafted polymers was controlled by varying the
      area of EB dose, and a minimal stripe pattern with a 200 nm line-width could be
      fabricated onto the surface. On the stripe-patterned surfaces, above the lower
      critical solution temperature (LCST), the cells initially adhered and spread with
      an orientation along the pattern direction. The magnitude of the spreading angle
      and elongation of adhered cells depended on the pattern intervals of the grafted
      PIPAAm. When culture temperature was lower than the LCST, cultured cells detached
      from the surfaces with strong shrinkage along the pattern direction, and
      sometimes folded and became parallel with the stripe pattern. This patterned cell
      recovery technique may be useful for the construction of muscle cell sheets with
      efficient shrinkage/relaxation in a specific direction and spheroidal 3D cell
      structures, with application to tissue engineering and microfluidic cellular
      devices.

PMID- 19157535
TI  - Covalent immobilisation of tropoelastin on a plasma deposited interface for
      enhancement of endothelialisation on metal surfaces.
AB  - Currently available endovascular metallic implants such as stents exhibit
      suboptimal biocompatibility in that they re-endothelialise poorly leaving them
      susceptible to thrombosis. To improve the interaction of these implants with
      endothelial cells we developed a surface coating technology, enabling the
      covalent attachment of biomolecules to previously inert metal surfaces. Using
      horseradish peroxidase as a probe, we demonstrate that the polymerised surface
      can retain the presentation and activity of an immobilised protein. We further
      demonstrated the attachment of tropoelastin, an extracellular matrix protein
      critical to the correct arrangement and function of vasculature. Not only it is
      structurally important, but it plays a major role in supporting endothelial cell
      growth, while modulating smooth muscle cell infiltration. Tropoelastin was shown
      to bind to the surface in a covalent monolayer, supplemented with additional
      physisorbed multilayers on extended incubation. The physisorbed tropoelastin
      layers can be washed away in buffer or SDS while the first layer of tropoelastin
      remains tightly bound. The plasma coated stainless steel surface with immobilised
      tropoelastin was subsequently found to have improved biocompatibility by
      promoting endothelial cell attachment and proliferation relative to uncoated
      stainless steel controls. Tropoelastin coatings applied to otherwise inert
      substrates using this technology could thus have broad applications to a range of
      non-polymeric vascular devices.

PMID- 19157538
TI  - Cationic glycolipids with cyclic and open galactose head groups for the selective
      targeting of genes to mouse liver.
AB  - Toward probing an hitherto unexplored structure-activity issue namely, the
      relative in vitro and in vivo efficacies of cationic glycolipids with cyclic and
      acyclic sugar heads for targeting of genes to liver, we have designed and
      synthesized two novel series of cationic glycolipids with cyclic (lipids 1-5) and
      open d-galactose heads (lipids 6-10) containing varying spacer arm lengths in
      between the sugar and positively charged nitrogen atoms. Among the cyclic
      glycolipids, lipid 3 with six methylene units spacer in between the quaternary
      nitrogen atom and among the glycolipids with the open-sugar heads, lipid 6 with
      only two methylene units spacer were found to be the most efficacious in
      targeting genes to cultured HepG2 (human hepatocarcinoma cells) and primary
      hepatocytes. Findings in the fluorescence resonance energy transfer (FRET)
      studies revealed biomembrane fusibilities as important physico-chemical
      parameters behind the varying spacer arm dependencies in the two series.
      Importantly, both the serum compatible glycolipids 3 &6 were found to be equally
      efficacious in selectively targeting genes to mouse livers under systemic
      settings. The significantly reduced efficiencies of the glycolipids 3 &6 in
      transfecting primary hepatocytes as well as mice pretreated with asialofetuin
      (the ligands of asialoglycoprotein receptors) support the notion that the
      cellular uptake of the lipoplexes prepared from both the open and the cyclic
      sugar-head series is mediated via asialoglycoprotein receptor. In summary, our
      present findings demonstrate for the first time that cationic glycolipids with
      cyclic sugar-head require longer spacer arms than their acyclic sugar-head
      counterparts for efficient gene transfection and both the series hold equal
      promise for selective gene targeting to liver under systemic settings.

PMID- 19157537
TI  - Cells and tissue interactions with glycated collagen and their relevance to
      delayed diabetic wound healing.
AB  - Dermal accumulation of advanced glycation end products (AGEs) has increasingly
      been implicated as the underlying cause of delayed diabetic wound healing.
      Devising an in vitro model to adequately mimic glycated tissues will facilitate
      investigation into the mechanism of glycation in conjunction with exploration of
      new approaches or improvement of current therapies for treating diabetic chronic
      wounds. Collagen matrices were artificially glycated and the presence of AGEs was
      demonstrated by immunostaining. Both the mechanical properties of the collagen
      matrices and their interactions with fibroblasts (morphology, attachment,
      proliferation, and migration) were altered after glycation, moreover, there was
      evidence of impairment on extracellular matrix (ECM) remodeling as well as
      inhibition of cell-induced material contraction. The actin cytoskeletons of the
      fibroblasts residing in the glycated collagen matrices were reorganized. In vivo
      mice full-thickness dermal wound models implanted with glycated collagen matrices
      showed delayed wound healing response. Thus, the glycated collagen matrix is an
      adequate in vitro model to mimic glycated tissues and could serve as a facile
      experimental tool to investigate the mechanism of glycation in conjunction with
      exploration of new approaches or improvement of current therapies for treating
      diabetic wounds.

PMID- 19157536
TI  - The effect of collagen I mimetic peptides on mesenchymal stem cell adhesion and
      differentiation, and on bone formation at hydroxyapatite surfaces.
AB  - Integrin-binding peptides increase cell adhesion to naive hydroxyapatite (HA),
      however, in the body, HA becomes rapidly modified by protein adsorption.
      Previously we reported that, when combined with an adsorbed protein layer, RGD
      peptides interfered with cell adhesion to HA. In the current study we evaluated
      mesenchymal stem cell (MSC) interactions with HA disks coated with the collagen
      mimetic peptides, DGEA, P15 and GFOGER. MSCs adhered equally well to disks coated
      with DGEA, P15, or collagen I, and all three substrates, but not GFOGER,
      supported greater cell adhesion than uncoated HA. When peptide-coated disks were
      overcoated with proteins from serum or the tibial microenvironment, collagen
      mimetics did not inhibit MSC adhesion, as was observed with RGD, however neither
      did they enhance adhesion. Given that activation of collagen-selective integrins
      stimulates osteoblastic differentiation, we monitored osteocalcin secretion and
      alkaline phosphatase activity from MSCs adherent to DGEA or P15-coated disks.
      Both of these osteoblastic markers were upregulated by DGEA and P15, in the
      presence and absence of differentiation-inducing media. Finally, bone formation
      on HA tibial implants was increased by the collagen mimetics. Collectively these
      results suggest that collagen-mimetic peptides improve osseointegration of HA,
      most probably by stimulating osteoblastic differentiation, rather than adhesion,
      of MSCs.

PMID- 19157539
TI  - Henning Schneider, M.D.
AB  - This is a short biography of Henning Schneider, M.D., Professor and Chair
      Emeritus of Obstetrics and Gynecology at the University of Bern, Switzerland.
      From 1987-2005, he was also Director of the Women's Hospital in Bern. Dr.
      Schneider was a founding member and the second President of the International
      Federation of Placenta Associations (IFPA). A symposium in Professor Schneider's
      honour was held at IFPA Meeting 2008.

PMID- 19157540
TI  - IP(3) receptor subtype-dependent activation of store-operated calcium entry
      through I(CRAC).
AB  - The store-operated, calcium release-activated calcium current I(CRAC) is
      activated by the depletion of inositol 1,4,5-trisphosphate (IP(3))-sensitive
      stores. The significantly different dose-response relationships of IP(3)-mediated
      Ca(2+) release and CRAC channel activation indicate that I(CRAC) is activated by
      a functionally, and possibly physically, distinct sub-compartment of the
      endoplasmic reticulum (ER), the so-called CRAC store. Vertebrate genomes contain
      three IP(3) receptor (IP(3)R) genes and most cells express at least two subtypes,
      but the functional relevance of various IP(3)R subtypes with respect to store
      operated Ca(2+) entry is completely unknown. We here demonstrate in avian B cells
      (chicken DT40) that IP(3)R type II and type III participate in IP(3)-induced
      activation of I(CRAC), but IP(3)R type I does not. This suggests that the
      expression pattern of IP(3)R contributes to the formation of specialized CRAC
      stores in B cells.

PMID- 19157541
TI  - Activation of the Ca2+-sensing receptor stimulates the activity of the epithelial
      Ca2+ channel TRPV5.
AB  - The extracellular Ca(2+)-sensing receptor (CaR) is a key-player in plasma Ca(2+)
      homeostasis. It is essentially expressed in the parathyroid glands and along the
      kidney nephron. The distal convoluted tubules (DCT) and connecting tubules (CNT)
      in the kidney are involved in active Ca(2+) reabsorption, but the function of the
      CaR has remained unclear in these segments. Here, the Ca(2+)-selective Transient
      Receptor Potential Vanilloid-subtype 5 channel (TRPV5) determines active Ca(2+)
      reabsorption by forming the apical entry gate. In this study we show that the CaR
      and TRPV5 co-localize at the luminal membrane of DCT/CNT. Furthermore, by patch
      clamp and Fura-2-ratiometric measurements we demonstrate that activation of the
      CaR leads to elevated TRPV5-mediated currents and increases intracellular Ca(2+)
      concentrations in cells co-expressing TRPV5 and CaR. Activation of CaR initiated
      a signaling cascade that activated phorbol-12-myristate-13-acetate (PMA)
      insensitive protein kinase C (PKC) isoforms. Importantly, mutation of two
      putative PKC phosphorylation sites, S299 and S654, in TRPV5 prevented the
      stimulatory effect of CaR activation on channel activity, as did a dominant
      negative CaR construct, CaR(R185Q). Interestingly, the activity of TRPV6, TRPV5'
      closest homologue, was not affected by the activated CaR. We conclude that
      activation of the CaR stimulates TRPV5-mediated Ca(2+) influx via a PMA
      insensitive PKC isoform pathway.

PMID- 19157542
TI  - Mechanisms operated by endothelin ETA and ETB receptors in the trigeminal
      ganglion contribute to orofacial thermal hyperalgesia induced by infraorbital
      nerve constriction in rats.
AB  - Endothelins, acting through specific endothelin ET(A) and/or ET(B) receptors,
      participate in nociceptive processing in models of cancer, inflammatory and
      neuropathic pain. The present study investigated which cell types express
      endothelin receptors in the trigeminal ganglion, and the contribution of
      mechanisms mediated by endothelin ET(A) and ET(B) receptors to orofacial heat
      hyperalgesia induced by unilateral constriction of the infraorbital nerve (CION).
      Both receptor types were identified by immunohistochemistry in the trigeminal
      ganglion, ET(A) receptors on small-sized non-myelinated and myelinated A-fibers
      and ET(B) receptors on both satellite glial cells and small-sized non-myelinated
      neuronal cells. CION promoted ipsilateral orofacial heat hyperalgesia which
      lasted from Day 2 until Day 10 after surgery. Ongoing CION-induced heat
      hyperalgesia (on Day 4) was reduced transiently, but significantly, by systemic
      or local treatment with antagonists of endothelin ET(A) receptors (atrasentan, 10
      mg/kg, i.v.; or BQ-123, 10 nmol/lip), endothelin ET(B) receptors (A-192621, 20
      mg/kg, i.v.; or BQ-788, 10 nmol/ lip), or of both ET(A)/ET(B) receptors
      (bosentan, 10 mg/kg, i.v.; or BQ-123 plus BQ-788, each at 10 nmol/lip). On the
      other hand, CION-induced heat hyperalgesia was transiently abolished over the
      first 90 min following i.p. injection of morphine hydrochloride (2.5 mg/kg), but
      fully resistant to reversal by indomethacin (4 mg/kg, i.p.) or celecoxib (10
      mg/kg, i.p.). Thus, heat hyperalgesia induced by CION is maintained, in part, by
      peripheral signaling mechanisms operated by ET(A) and ET(B) receptors. Endothelin
      receptors might represent promising therapeutic targets for the control of
      trigeminal neuropathic pain.

PMID- 19157543
TI  - Decitabine-induced effusions.

PMID- 19157544
TI  - Uncommon lineage switch warrants immunophenotyping even in relapsing leukemia.

PMID- 19157545
TI  - Assessment of ATRX expression in patients with myelodysplastic syndromes treated
      with decitabine.

PMID- 19157546
TI  - Chemo-sensitivity in a panel of B-cell precursor acute lymphoblastic leukemia
      cell lines, YCUB series, derived from children.
AB  - Sensitivity to 10 anticancer drugs was evaluated in 6 childhood B-cell precursor
      acute lymphoblastic leukemia (BCP-ALL) cell lines. Authenticity of newly
      established cell lines was confirmed by genomic fingerprinting. The line YCUB-5R
      established at relapse was more resistant to 4-hydroperoxy-cyclophosphamide,
      cytarabine, L-asparaginase, topotecan, fludarabine, and etoposide than YCUB-5
      from the same patient at diagnosis. Of the drugs tested, etoposide and SN-38
      (irinotecan) showed highest efficacy in the panel, with 50% growth inhibition at
      0.22-1.8 microg/ml and 0.57-3.6 ng/ml, respectively. This cell line panel offers
      an in vitro model for the development of new therapies for childhood BCP-ALL.

PMID- 19157547
TI  - Monitoring minimal residual disease with flow cytometry, antigen-receptor gene
      rearrangements and fusion transcript quantification in Philadelphia-positive
      childhood acute lymphoblastic leukemia.
AB  - In this study, we followed minimal residual disease (MRD) in eight children with
      Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) using (i) flow
      cytometry (FCM), (ii) real-time quantitative PCR of IG/TCR gene rearrangements
      and (iii) RT-PCR detecting fusion gene transcripts. In six of the eight cases the
      kinetics of MRD clearance was comparable. One of the two discordant cases could
      be explained by presence of an alternative fusion transcript. The other
      discordant case showed high BCR-ABL1 RNA level while the other methods did not
      detect any MRD. In our limited material quantitative RT-PCR of fusion gene
      transcripts seemed particularly useful to measure MRD in Ph+ ALL. However, BCR
      ABL1 expression may not reflect the percentage of leukemic cells as FCM and
      IG/TCR rearrangement quantification do, and these methods are thus complementary.

PMID- 19157548
TI  - Lymphangiogenesis in haematological malignancies.

PMID- 19157549
TI  - Polymorphisms of DNA repair genes and susceptibility to acute childhood
      lymphoblastic leukemia.

PMID- 19157550
TI  - Nelarabine induced complete remission in an adult with refractory T-lineage acute
      lymphoblastic leukemia: A case report and review of the literature.

PMID- 19157551
TI  - Fetal magnetic resonance imaging in midline malformations of the central nervous
      system and review of the literature.
AB  - Fetal magnetic resonance imaging (MRI) is a well-established second line imaging
      modality in identifying complex pathologies of the central nervous system (CNS),
      especially when ultrasound (US) findings are equivocal. It may enable an early
      and precise diagnosis, which is essential in terms of management of pregnancy and
      pre-, peri- and postnatal care. We present three cases with rare complex midline
      malformations of the CNS, diagnosed prenatally by fetal MRI. Two cases revealed
      holoprosencephaly; one case demonstrated rhombencephalosynapsis. In addition, we
      reviewed the literature and provide a summary of recent findings regarding
      cerebral midline development and discuss the advantages of fetal MRI.

PMID- 19157552
TI  - Bacterial endotoxin activates retinal pigment epithelial cells and induces their
      degeneration through IL-6 and IL-8 autocrine signaling.
AB  - Inflammation is a major contributing factor to many blinding disorders including
      uveitis, diabetic retinopathy, and age-related macular degeneration. Here we
      examined the response of the retinal pigment epithelium (RPE) to physiological
      levels of lipopolysaccharide (LPS) to understand the role of this epithelium in
      inflammatory retinal conditions. Expression of a group of inflammatory mediators
      was identified by gene array analysis and confirmed by PCR and
      immunocytochemistry in primary human RPE cultures and ARPE19. The effects of LPS
      on the expression of these cytokines and RPE survival were examined by PCR,
      Luminex bead, and MTT assays. RPE cells express many cytokine receptors including
      IL-1R, -4R, -6R, -8RA, IFNAR1, IFNGR1/2 and secrete a range of pro- and anti
      inflammatory cytokines including IL-4, -6, -8, -10, -17, IFN-gamma, MCP-1, and
      VEGF. LPS increases IL-13RA1 and IFNAR1, and decreases IL-7R receptor expression.
      It also increases RPE secretion of IL-4, -6, -8, -10, IFN-gamma and MCP-1, and is
      toxic to RPE cells at LC(50)=17.7 microg/ml. LPS toxicity is mediated by IL-6 and
      IL-8 through an autocrine feedback loop. Silencing IL-6R and IL-8RA gene
      expression by siRNA blocks death by their respective ligands or LPS. These
      findings imply that RPE cells are acutely sensitive to inflammatory stress and
      that over secretion of IL-6 and IL-8 by this epithelium during inflammatory
      stimulus may be an underlying factor in the progression of some retinal
      pathologies.

PMID- 19157553
TI  - The peptide length specificity of some HLA class I alleles is very broad and
      includes peptides of up to 25 amino acids in length.
AB  - The major ligands presented by MHC class I molecules after natural antigen
      processing are peptides of eight to ten residues in length, and it is widely
      accepted that the binding preferences of MHC class I molecules play a dominant
      role in dictating this classic feature of antigen presentation. In this report,
      we have reassessed the peptide size specificity of class I human leukocyte
      antigens (HLAs). By lengthening previously defined T cell epitopes by central
      amino acid insertion, we demonstrate that the peptide length specificity of some
      common HLA class I alleles (HLA-B*3501, B*0702 and A*2402) is very broad, and
      includes peptides of up to 25 residues. These data suggest that the length
      limitation of naturally processed MHC class I-associated peptides is primarily
      controlled by peptide availability after antigen processing rather than the
      binding specificity of MHC class I molecules. Furthermore, the findings provide
      an explanation for recent reports highlighting that epitopes of >10 amino acids
      play a minor but significant role in virus-specific immune surveillance by CD8(+)
      T cells.

PMID- 19157554
TI  - Structural basis for the function of anti-idiotypic antibody in immune memory.
AB  - We had earlier proposed a hypothesis to explain the mechanism of perpetuation of
      immunological memory based on the operation of idiotypic network in the complete
      absence of antigen. Experimental evidences were provided for memory maintenance
      through anti-idiotypic antibody (Ab(2)) carrying the internal image of the
      antigen. In the present work, we describe a structural basis for such memory
      perpetuation by molecular modeling and structural analysis studies. A three
      dimensional model of Ab(2) was generated and the structure of the antigenic site
      on the hemagglutinin protein H of Rinderpest virus was modeled using the
      structural template of hemagglutinin protein of Measles virus. Our results show
      that a large portion of heavy chain containing the CDR regions of Ab(2) resembles
      the domain of the hemagglutinin housing the epitope regions. The similarity
      demonstrates that an internal image of the H antigen is formed in Ab(2), which
      provides a structural basis for functional mimicry demonstrated earlier. This
      work brings out the importance of the structural similarity between a domain of
      hemagglutinin protein to that of its corresponding Ab(2). It provides evidence
      that Ab(2) is indeed capable of functioning as surrogate antigen and provides
      support to earlier proposed relay hypothesis which has provided a mechanism for
      the maintenance of immunological memory.

PMID- 19157555
TI  - Surface expression of a C-terminal alpha-helix region in heat shock protein 72 on
      murine LL/2 lung carcinoma can be recognized by innate immune sentinels.
AB  - Surface expression of Hsp70 members has been previously reported on human tumor
      cell lines. Here we examined how the inducible mouse Hsp72 can be expressed on
      the surface of two types of murine tumor cell lines in response to non-lethal
      heat shock. Exposure to 42 degrees C for 2h led to the intracellular production
      of Hsp72 for both murine LL/2 lung carcinoma and B16 melanoma cells. Flow
      cytometric analyses showed that living LL/2 carcinoma, but not B16 melanoma,
      transported a fraction of inducible Hsp72 to the cell-surface membrane. Induction
      of the surface expression of Hsp72 occurred upon non-lethal heat shock only when
      Hsp72 expression was forced to be elevated in B16 transfectants. Hsp72 expressed
      on the LL/2 cell surface was detected by the monoclonal antibody that recognized
      the epitope of 504-617 amino acid residues, but not by another antibody with the
      epitope of 122-264 residues. When we analyzed the binding of recombinant full
      length Hsp72 to mouse splenocytes, significant binding was observed for innate
      immune cells such as CD11b(+)-, CD11c(+)-, or NK1.1(+)-cells. The recombinant
      variants obtained by truncation of the C-terminal helical region of Hsp72
      exhibited more robust binding to these innate immune cells in a similar fashion,
      however, further deletion offered less binding to those immunocytes. Two fragment
      variants lacking the N-terminal nucleotide-binding domain were found to
      extensively bind to peritoneal macrophages. Taken together with these results, it
      thus follows that the sentinels in an innate immune system, macrophages,
      dendritic cells and NK cells, can be involved in the surveillance of functionally
      aberrant cells through the recognition of a specific C-terminal structure of
      Hsp70 as a danger signal in living cells.

PMID- 19157556
TI  - Toll-like receptor 7 cooperates with IL-4 in activated B cells through antigen
      receptor or CD38 and induces class switch recombination and IgG1 production.
AB  - IL-4 and 8-mercaptoguanosine (8-SGuo) stimulation of CD38-activated B cells
      induces mu to gamma1 class switch recombination (CSR) at the DNA level leading to
      a high level of IgG1 production. Although some of signaling events initiated by
      IL-4 in activated B cells have been characterized, the involvement of TLR/MyD88
      and Btk pathway in IL-4-dependent mu to gamma1 CSR has not been thoroughly
      evaluated. In this study, we characterized receptors for 8-SGuo and differential
      roles of 8-SGuo and IL-4 in the induction and mu to gamma1 CSR and IgG1
      production. The role of TLR7 and MyD88 in 8-SGuo-induced AID expression and mu to
      gamma1 CSR was documented, as 8-SGuo did not act on CD38-stimulated splenic B
      cells from Tlr7(-/-) and Myd88(-/-) mice. CD38-activated B cells from Btk
      deficient mice failed to respond to TLR7 ligands for the AID expression and CSR,
      indicating that Btk is also indispensable for the system. Stimulation of CD38
      activated B cells with 8-SGuo induced significant AID expression and DNA double
      strand breaks, but IL-4 stimulation by itself did not trigger mu to gamma1 CSR.
      Intriguingly, the mu to gamma1 CSR in the B cells stimulated with CD38 and 8-SGuo
      totally depends on IL-4 stimulation. Similar results were obtained in the
      activated B cells through BCR and loxoribine, a well-known TLR7 ligand, in place
      of 8-SGuo. In vivo administration of TLR7 ligand and anti-CD38 antibody induced
      the generation of CD138(+) IgG1(+) cells. These results indicate that TLR7 is a
      receptor for 8-SGuo and plays an essential role in the AID and Blimp-1
      expression; however it is not enough to complete mu to gamma1 CSR in CD38
      activated B cells. IL-4 may be required for the induction of DNA repair system
      together with AID for the completion of CSR.

PMID- 19157557
TI  - Chemoreduction for group E retinoblastoma: comparison of chemoreduction alone
      versus chemoreduction plus low-dose external radiotherapy in 76 eyes.
AB  - PURPOSE: To evaluate chemoreduction (CRD) for group E retinoblastoma. DESIGN:
      Retrospective, comparative case series. PARTICIPANTS: Seventy-six eyes of 56
      patients with group E retinoblastoma were treated with CRD alone or CRD plus low
      dose prophylactic external beam radiotherapy (CRD+P-EBR). The CRD included
      vincristine, etoposide, and carboplatin (6 cycles). The P-EBR was given routinely
      2 months after completion of CRD at a suggested dose of 2600 cGy. Therapeutic EBR
      (T-EBR) was only given at the time of extensive tumor recurrence at a suggested
      dose of 3800 cGy. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES:
      Globe salvage. RESULTS: Of the 76 eyes, 64 received CRD alone and 12 received
      CRD+P-EBR. At the 2-year follow-up, globe salvage was achieved in 29 (53%) of 55
      eyes in the CRD group and in 10 (91%) of 11 eyes in the CRD+P-EBR group. At 5
      years, globe salvage was achieved in 20 (48%) of 42 eyes in the CRD group and in
      4 (80%) of 5 eyes in the CRD+P-EBR group (P=0.347). Of the 64 eyes in the CRD
      group, 16 (25%) were salvaged with CRD alone and 13 (20%) with CRD+T-EBR, whereas
      22 (34%) were enucleated after CRD alone and 13 (20%) were enucleated after CRD+T
      EBR. Of the 12 eyes in the CRD+P-EBR group, 10 (83%) were salvaged with CRD+P
      EBR, whereas 2 (17%) were enucleated and none required T-EBR. The median dose for
      T-EBR was 3800 cGy, and that for P-EBR was 2600 cGy. Eyes treated with CRD+P-EBR
      showed significantly less recurrence, leading to less chance of enucleation or
      therapeutic radiotherapy than that for CRD alone (P<0.001). Visual acuity was
      20/100 or better or fix and follow in 9 (32%) of 28 salvaged eyes in the CRD
      group and in 4 (40%) of 10 in the CRD+P-EBR group. At 5 years, there were no
      patients in either group with metastasis of pinealoblastoma or who had died. In
      one patient in the CRD group, a second cancer developed. CONCLUSIONS: Group E
      retinoblastoma managed with CRD+P-EBR showed significantly less need for
      enucleation or therapeutic radiotherapy than eyes treated with CRD alone. These
      findings merit further study and consideration.

PMID- 19157558
TI  - Ultrasound biomicroscopic features associated with angle closure in fellow eyes
      of acute primary angle closure after laser iridotomy.
AB  - PURPOSE: To investigate the frequency of appositional angle closure and related
      anatomic characteristics in fellow eyes of Chinese subjects with acute primary
      angle closure (APAC) after laser peripheral iridotomy (LPI). DESIGN: Cross
      sectional study. PARTICIPANTS: Consecutive subjects with APAC presenting from
      April 2006 to September 2006 at the Glaucoma Service of Peking University Eye
      Center, Peking University Third Hospital. METHODS: Under dark conditions, fellow
      eyes were divided into 2 groups based on the detection of appositional angle
      closure by ultrasound biomicroscopy (UBM). For all subjects, UBM parameters were
      measured to evaluate the different anatomic features between the 2 groups.
      Darkroom provocative tests (DRPTs) and gonioscopy were performed to investigate
      the relationship between angle closure and intraocular pressure. MAIN OUTCOME
      MEASURES: Central anterior chamber depth (ACD); angle opening distance(500)
      (AOD(500)); angle recess area(750) (ARA(750)); trabecular-iris angle (T-I angle);
      trabecular-ciliary process distance (TCPD); peripheral iris thickness (IT(1));
      iris-zonule distance (IZD); and the position of the iris insertion. RESULTS:
      Thirty-four post-LPI fellow eyes of 34 patients with APAC (8 men, 26 women; mean
      +/- standard deviation age 66.3+/-7.2 years, range 54-83) were included.
      Peripheral anterior synechiae (PAS) were not observed in any subject.
      Appositional angle closure was observed in at least 1 quadrant in 13 (38.2%) of
      the 34 patients. Compared with eyes without appositional closure, eyes with
      appositional closure showed significantly lower AOD(500), ARA(750), and T-I angle
      in 4 quadrants; shorter TCPD in the inferior and temporal quadrants; and thicker
      IT(1) in the superior and nasal quadrants (P<0.05). The DRPT results were
      positive in 3 (11.1%) of 27 eyes with appositional closure in 0 to 2 quadrants
      and in 3 (75.0%) of 4 eyes with appositional closure in 3 to 4 quadrants (P =
      0.0164). CONCLUSIONS: Under dark conditions, more than one third of fellow eyes
      of APAC showed appositional angle closure after LPI. The anatomic findings
      indicate a narrower angle, a more anterior position of the ciliary body, and a
      thicker peripheral iris in fellow eyes of APAC after LPI may be associated with
      an increased risk for progressive angle closure.

PMID- 19157559
TI  - Comparing diurnal and nocturnal effects of brinzolamide and timolol on
      intraocular pressure in patients receiving latanoprost monotherapy.
AB  - PURPOSE: To compare the diurnal and nocturnal effects of brinzolamide and timolol
      on intraocular pressure (IOP) in patients already receiving monotherapy with
      latanoprost. DESIGN: Prospective, open-label, and crossover clinical trial.
      PARTICIPANTS: Twenty-six patients with glaucoma or ocular hypertension (ages, 44
      79 years) who were receiving treatment with 0.005% latanoprost once every
      evening. METHODS: Baseline data of 24-hour IOP were collected in a sleep
      laboratory while patients were receiving latanoprost monotherapy. Measurements
      were taken every 2 hours in the sitting and supine positions during the 16-hour
      diurnal/wake period and in a supine position during the 8-hour nocturnal/sleep
      period. Patients were randomly assigned to receive an add-on treatment with
      either 1% brinzolamide 3 times per day or 0.5% timolol gel forming solution once
      every morning for 8 weeks, and then crossed over to receive the other add-on
      treatment. At the end of each add-on treatment period, 24-hour IOP data were
      collected. MAIN OUTCOME MEASURES: Diurnal and nocturnal IOP means were compared
      among the baseline, the brinzolamide add-on treatment, and the timolol add-on
      treatment. RESULTS: During the diurnal period, the mean IOP under brinzolamide or
      timolol add-on treatment was significantly lower than the baseline IOP in both
      the sitting and supine positions. There was no statistical difference between the
      2 add-on treatments. During the nocturnal period, the supine IOP under
      brinzolamide add-on treatment was significantly lower than both the baseline and
      the timolol add-on treatment. There was no difference in nocturnal IOP between
      the timolol add-on treatment and the baseline. CONCLUSIONS: In patients already
      receiving the latanoprost monotherapy, adding brinzolamide or timolol
      significantly reduced IOP during the diurnal period. However, only the
      brinzolamide add-on treatment had an IOP-lowering efficacy during the nocturnal
      period.

PMID- 19157560
TI  - A change in oxygen supplementation can decrease the incidence of retinopathy of
      prematurity.
AB  - PURPOSE: To determine the incidence of retinopathy of prematurity (ROP) over a 2
      year period before and after a change in the practice of oxygen supplementation.
      DESIGN: Nonrandomized, retrospective study. PARTICIPANTS: All infants in a single
      Level III neonatal intensive care unit between the years of 2005 and 2007.
      METHODS: A prospective database recorded the gestational age, birth weight, stage
      and zone of ROP, threshold disease, treatment, final outcome and date of
      examination, maternal and infant demographics, and neonatal intensive care unit
      course. Year 1 (August 1, 2005 to July 31, 2006) includes a patient cohort who
      received the standard oxygen supplementation protocol, which has oxygen targets
      of 95% to 100% saturation. Year 2 (August 1, 2006 to July 31, 2007) includes a
      patient cohort who has strictly monitored oxygen targets of <34 weeks corrected
      gestational age oxygen limits of 80% to 95% and target 85% to 92% oxygen
      saturation and >34 weeks corrected gestational age limits of 85% to 100% and
      target 92% to 97% saturation. MAIN OUTCOME MEASURE: Incidence of ROP in year 1
      before a change in oxygen protocol compared with the incidence of ROP in year 2
      after a change in the oxygen protocol. RESULTS: A total of 114 children in year 1
      and 108 children in year 2 were identified as having been born or transferred to
      the Fairview Nursery. Ninety-eight infants were examined before and 92 infants
      were examined after the change in oxygen standards, comprising 190 consecutive
      patients examined between September 2005 and October 2007. ROP was present in 35%
      of infants in group 1 before the change in oxygen protocol compared with 13%
      after the change in oxygen standards (P=0.001); stage 3 decreased from 11% to 2%
      (P=0.021); threshold disease decreased from 7% to 1% (P=0.066). Stage 0 (immature
      vessels, no ROP) incidence increased (pre/post-oxygen change 30%/51% stage 0,
      P=0.001). There were statistically significant differences in mode of delivery
      (P=0.007), sepsis <3 days of life (P=0.01), and oxygen at discharge (P=0.003).
      CONCLUSIONS: Lower oxygen targets at early gestational age and higher oxygen
      targets at older gestational age decrease the severity and incidence of ROP while
      inducing normal retinal development.

PMID- 19157561
TI  - Long-term incidence and timing of intraocular hypertension after intravitreal
      triamcinolone acetonide injection.
AB  - PURPOSE: To describe the long-term incidence and timing of steroid-induced ocular
      hypertension after intravitreal triamcinolone acetonide (IVTA) therapy. DESIGN:
      Retrospective case series of 929 eyes of 841 patients. PARTICIPANTS: Patients
      with a variety of posterior segment disorders in a single group practice.
      INTERVENTION: Pars plana injection of IVTA. MAIN OUTCOME MEASURES: Intraocular
      pressure (IOP) and requirement for glaucoma surgery. RESULTS: Overall, 929 eyes
      received >or=1 injections (mean, 1.6) of 4 mg of IVTA. During a mean follow-up
      period of 14+/-6.9 months, the Kaplan-Meier cumulative incidences of IOP
      elevations >21 mmHg at 6, 12, 18, and 24 months post-injection were 28.2%, 34.6%,
      41.2%, and 44.6%, respectively; similarly, the incidences of eyes with IOP
      measurements >25 mmHg were 14.6%, 19.1%, 24.1%, and 28.2%, respectively. At the
      same time points, IOP-lowering medications were required by 13.0%, 16.9%, 20.7%,
      and 24.2% of eyes, respectively. Only 3 eyes (0.3%) required IOP-lowering
      surgery. Preexisting glaucoma, younger age, and a history of an IOP elevation
      after a previous IVTA injection were risk factors for IOP elevations after IVTA
      injection. The minimum and maximum follow-up were 3 weeks and 37 months. The mean
      rate of attrition in this study was 3% per month. CONCLUSIONS: Elevations in IOP
      after IVTA injection are common. Younger patients and eyes with preexisting
      glaucoma or a history of a steroid response should be monitored more closely for
      IOP elevations after IVTA therapy.

PMID- 19157562
TI  - Economic implications of current age-related macular degeneration treatments.
AB  - PURPOSE: To measure the cost versus benefit of age-related macular degeneration
      (AMD) treatment strategies, existing and proposed, in the postranibizumab era.
      DESIGN: Cost-effectiveness model. PARTICIPANTS: None. METHODS: University with
      hospital-based practice modeling of clinical examination, imaging, and treatment
      schedules were constructed considering published protocols where available, or by
      estimating usual practices. Medicare-allowable reimbursement schedules for a
      hospital-based, south Florida practice in 2007 were used to calculate costs of
      treatment. The lines of vision saved were deduced from published reports or using
      identified assumptions. This information was used to calculate cost per lines
      saved and, using actuarial tables data, costs per line-year saved were
      calculated. MAIN OUTCOME MEASURE: Cost ($US) per line-year. RESULTS: Consensus
      control values of expected lines loss if untreated (natural history) were
      established from published reports (2.5 lines at 1 year; 3.5 at 2 years) and
      photodynamic therapy (2.0 lines at 1 year; 3.0 at 2 years) for use in calculating
      lines of vision saved in studies without untreated control groups. The cost per
      line-year for 1 year of treatment ranged from a low of $84 with as-needed
      bevacizumab to $766 for protocol-style use of ranibizumab. Combination treatment
      regimens yielded a range of $71 to $269. The pharmaceutical proportion of
      treatment costs is higher than professional or facility costs, ranging to 83% for
      protocol-style ranibizumab. CONCLUSIONS: Pharmaceutical-based treatments of AMD
      have markedly improved visual outcomes, but also have escalated costs markedly.
      Treatment regimens involving as-needed dosing, alternate medications, and
      combination therapy may preserve benefit for substantially lower costs. Disparate
      safety profiles would require consideration in choosing treatment regimens. Cost
      benefit issues must be considered in AMD treatment regimens.

PMID- 19157563
TI  - Peripheral exudative hemorrhagic chorioretinopathy simulating choroidal melanoma
      in 173 eyes.
AB  - PURPOSE: To evaluate the clinical features and outcomes of eyes with peripheral
      exudative hemorrhagic chorioretinopathy (PEHCR) simulating choroidal melanoma.
      DESIGN: Noncomparative case series. PARTICIPANTS: A total of 173 eyes in 146
      patients. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Clinical
      features and outcome. RESULTS: All cases were referred for possible choroidal
      melanoma. The mean patient age was 80 years, 145 (99%) were Caucasian, and 98
      (67%) were female. The main lesion had a mean diameter of 10 mm and mean
      thickness of 3 mm. The lesion was located temporally in 103 eyes (77%), involved
      1 or 2 quadrants in 123 eyes (92%), and was located between the equator and the
      ora serrata in 119 eyes (89%). Features included subretinal hemorrhage in 134
      eyes (78%), retinal exudation in 37 eyes (21%), retinal pigment epithelial (RPE)
      detachment in 48 eyes (28%), and sub-RPE hemorrhage in 45 eyes (26%). Peripheral
      RPE alterations or drusen were found in 120 ipsilateral eyes (69%) and 73
      contralateral eyes (42%). Macular RPE alterations, drusen, or choroidal
      neovascularization was found in 83 ipsilateral eyes (48%) and 97 contralateral
      eyes (56%). After observation (mean 15 months), lesion regression or stability
      was found in 80 eyes (89%) and progression was found in 10 eyes (11%).
      CONCLUSIONS: PEHCR is a hemorrhagic retinal degenerative process that simulates
      choroidal melanoma.

PMID- 19157564
TI  - Season of birth, daylight hours at birth, and high myopia.
AB  - PURPOSE: Mandel et al recently reported that season of birth and daylight hours
      (photoperiod) at birth were associated with moderate and high levels of myopia in
      Israeli conscripts. We sought to investigate whether these associations were
      evident in subjects from the United Kingdom (UK). DESIGN: Retrospective cross
      sectional study. PARTICIPANTS: The study population comprised 74,459 subjects
      aged 18 to 100 years attending UK optometry practices for an eye examination.
      METHODS: Data comprising non-cycloplegic spectacle prescription, sex, date of
      birth, and date of eye examination were collected from UK optometry practices.
      The average refractive error in fellow eyes was used to classify the degree of
      myopia in diopters (D) for each subject as follows: absent (>-0.75 D), low (-0.75
      to -2.99 D), moderate (-3.00 to -5.99 D), or high (<-6.00 D). The average monthly
      hours of daylight for London, UK, were classified into 1 of 4 "photoperiod
      categories," following Mandel et al. The odds ratio (OR) for each level of
      severity of myopia was calculated using multivariate logistic regression with
      age, sex, and either season of birth or photoperiod category as risk factors.
      MAIN OUTCOME MEASURES: The OR for season of birth and photoperiod category as
      potential risk factors for myopia. RESULTS: Season of birth was significantly
      associated with the presence of high myopia: Subjects born in summer or autumn
      were more likely to be highly myopic compared with those born in winter (summer
      OR=1.17; 95% confidence interval [CI], 1.05-1.30; P=0.006; autumn OR=1.16; 95%
      CI, 1.04-1.30; P=0.007). However, season of birth was not a significant risk
      factor for low or moderate myopia. Photoperiod category was weakly associated
      with low myopia (OR=0.94; 95% CI, 0.89-0.99; P=0.019), but with a direction of
      effect opposite to that observed by Mandel et al. CONCLUSIONS: As in Israel, a
      disproportionate number of UK high myopes were born in summer or autumn rather
      than in winter. However, unlike the situation in Israel, this association does
      not seem to be related to daylight hours during the postnatal period, implicating
      alternative physiologic influences that vary with season, such as birth weight.

PMID- 19157565
TI  - Synthesis, double stranded DNA-binding and photocleavage studies of a
      functionalized ruthenium(II) complex with 7,7'-methylenedioxyphenyldipyrido[3,2
      a:2',3'-c]-phenazine.
AB  - A new Ru(II) complex [Ru(phen)(2)(mdpz)](2+) (phen=1,10-phenanthroline, mdpz=7,7'
      methylenedioxyphenyl-dipyrido-[3,2-a:2',3'-c]phenazine) has been synthesized and
      characterized in detail by elemental analysis, mass spectrometry and (1)H NMR
      spectroscopy. The interaction of the complex with calf thymus DNA was
      investigated by spectroscopic and viscosity measurements. The results suggest
      that the complex binds to DNA via an intercalative mode and serves as a molecular
      "light switch" for DNA. Moreover, the complex has been found to promote the
      photocleavage of plasmid DNA pBR322 under irradiation at 365 nm. The mechanism
      studies reveal that singlet oxygen ((1)O(2)) plays a significant role in the
      photocleavage.

PMID- 19157566
TI  - Speed of response to threshold and suprathreshold bilateral ECT in depression,
      mania and schizophrenia.
AB  - BACKGROUND: Bilateral electroconvulsive therapy (BLECT) is useful in affective
      disorders and schizophrenia. Studies on electrical dose during BLECT are sparse.
      The Royal College of Psychiatrists recommends the use of electrical dose at 50
      100% above seizure threshold. We studied the impact of change of BLECT practice
      from using threshold-level to 1.5 times threshold-level electrical dose in
      patients with depression, mania and schizophrenia. METHOD: Data of 100
      consecutive inpatients who received BLECT at threshold-level was compared with
      that of 101 who received BLECT at 1.5 times threshold-level. Patients in the two
      groups were comparable in sociodemographic and clinical details. In all patients
      ECT was stopped after patients had shown clinical improvement. Number of ECTs
      required to achieve improvement and the number of inpatient days after the start
      of ECT formed the outcome measures. RESULTS: Overall, there was no significant
      difference between the groups in the outcome variables. However, when diagnoses
      were considered separately, patients with mania who received threshold-level
      needed about 2 more ECT sessions (t=2.6; p=0.01) and stayed for about 10 more
      days as inpatients (t=2.4; p=0.03) than those who received 1.5 times threshold
      level BLECT. LIMITATIONS: The study is chart-based, with its inherent
      limitations. Standard outcome measures were not used. Cognitive adverse effects
      were not studied. CONCLUSIONS: Patients with schizophrenia and depression treated
      with BLECT at 1.5 times threshold-level electrical stimulus require similar
      number of ECT sessions as with threshold-level. However, patients with mania show
      clinical improvement with significantly fewer ECT sessions if treated at
      suprathreshold stimulus.

PMID- 19157567
TI  - Thoracic duct cannulation without thoracotomy in sheep: a method for accessing
      efferent lymph from the lung.
AB  - We have developed and validated a novel method to access efferent lymph draining
      the lung and gut of sheep. In this model, efferent lymph derived from the lung
      could be collected via cannulation of the thoracic duct just prior the thoracic
      duct-jugular vein junction. The thoracic duct was accessed in the neck region
      without needing to broach the thoracic cavity, thus avoiding extensive tissue
      damage to the animal and need for ventilation during surgery. In addition, this
      surgical approach allows for a second cannulation of an adjacent lymphatic
      draining the head/neck region, providing for an 'in-built' internal control with
      which to compare lymph parameters. To test the verity of cannulation procedure, a
      test protein ovalbumin (OVA) was infused into the left and right lungs via
      bronchoscopy. We found that OVA was recovered almost exclusively in the lymph
      draining the lungs compared to the lymph draining the head/neck where it was
      essentially non-existent. The method described here will be invaluable for
      optimizing intra-lung delivery of drugs or vaccines. In addition, access to lymph
      will also allow for analysis of immune responses to infections originating at
      this site.

PMID- 19157568
TI  - Molecular analysis of tammar (Macropus eugenii) mammary epithelial cells
      stimulated with lipopolysaccharide and lipoteichoic acid.
AB  - The immunological function of the metatherian mammary gland plays a crucial part
      in neonatal survival of the marsupial young. Marsupial pouch young do not develop
      adult like immune responses until just prior to leaving the pouch. The immune
      components of the maternal milk secretions are important during this vulnerable
      early post-partum period. In addition, infection of the mammary gland has not
      been recognized in metatherians, despite the ready availability of pathogens in
      the pouch. Regardless of which, little is known about the immunobiology of the
      mammary gland and the immune responses of mammary epithelial cells in
      metatherians. In this study, a molecular approach was utilized to examine the
      response of tammar (Macropus eugenii) mammary epithelial cells to Escherichia
      coli derived lipopolysaccharide (LPS) and Staphylococcus aureus derived
      lipoteichoic acid (LTA). Using custom-made cDNA microarrays, candidate genes were
      identified in the transciptome, which were involved in antigen presentation,
      inflammation, cell growth and proliferation, cellular damage and apoptosis.
      Quantification of mRNA expression of several of these candidate genes, along with
      seven other genes (TLR4, CD14, TNF-alpha, cathelicidin, PRDX1, IL-5 and ABCG2)
      associated with innate immunity in LPS and LTA challenged mammary epithelial
      cells and leukocytes, was assessed for up to 24 h. Differences in genes
      associated with cellular damage and pro-inflammatory cytokine production were
      seen between stimulated mammary epithelial cells and leukocytes. LTA challenge
      tended to result in lower level induction of pro-inflammatory cytokines,
      increased PRDX1 mRNA levels, suggesting increased oxidative stress, and increased
      CD14 expression, but in a non-TLR4-dependent manner. The use of functional
      genomic tools in the tammar identified differences in the response of tammar
      mammary epithelial cells (MEC) and leukocytes to challenge with LPS and LTA, and
      validates the utility of the approach. The results of this study are consistent
      with a model in which tammar mammary epithelial cells have the capacity to elicit
      a complex and robust immune response to pathogens.

PMID- 19157569
TI  - Adjuvants for porcine reproductive and respiratory syndrome virus vaccines.
AB  - This review deals with present and past efforts in utilization of vaccine
      adjuvants for porcine reproductive and respiratory syndrome virus (PRRSV)
      vaccines. PRRSV vaccines elicit delayed and weak cell-mediated immune (CMI) and
      antibody responses after vaccination. Several kinds of vaccine adjuvants have
      been utilized to accelerate and magnify immune responses to PRRSV vaccines. These
      adjuvants include cytokines, chemical reagents, and bacterial products. Of 11
      vaccine adjuvants tested, five (i.e. interleukin-2 (IL-2), IL-12, interferon
      alpha (IFNalpha), polyinosinic and polycytidylic acid, and cytidine-phosphate
      guanosine oligodeoxynucleotides (CpG ODN)) significantly enhance CMI response to
      PRRSV vaccines. The response is characterized by proliferation, cytotoxicity, and
      IFNgamma secretion of peripheral blood mononuclear cells or T cells in response
      to recall PRRSV antigens in vitro. Two (i.e. CpG ODN and cholera toxin)
      significantly enhance PRRSV-specific antibody response after vaccination. Two
      (i.e. IL-2 and CpG ODN) significantly enhance protective efficacy of PRRSV
      vaccines in challenge models. Improvement of immune responses to PRRSV vaccines
      should focus in future studies on assessing more vaccine adjuvants for their
      efficiency in enhancing both CMI and antibody responses and on identifying PRRSV
      components and strategies that down-modulate pig immune responses in order to
      devise vaccine adjuvants that can regulate such strategies of the virus.

PMID- 19157570
TI  - Cutaneous cytokine gene expression and cellular responses in lambs infested with
      the louse, Bovicola ovis, and following intradermal injection of crude louse
      antigen.
AB  - The present study was undertaken to investigate further the immunological
      responses in the skin of lambs to natural louse infestation and following
      intradermal allergen challenge. Bovicola ovis-infested (n=7) and naive (n=7)
      Romney lambs received four intradermal injections each of crude louse Ag and
      diluent control solutions on the dorso-lateral chest. From each lamb, skin
      samples were obtained from untreated skin and, at 4, 24, 48 and 72 h following
      injection, from one each of the Ag- and diluent-injected skin sites. Levels of
      acetylcholinesterase-positive Langerhans and MHC II(+) cells in the epidermis as
      well as MHC II(+), CD1b(+), T19(+) and IgE(+) cells, eosinophils, and diffuse IgE
      staining in the dermis were significantly elevated in infested compared to naive
      lambs (all p< or =0.01). Additionally, gene expression of interleukin-4 (IL-4),
      IL-5, IL-13 (all p< or =0.001) and IL-10 (p< or =0.05) was significantly higher
      in the skin of infested compared to naive lambs while TNF-alpha and IFN-gamma
      gene expression were not significantly different between the two groups.
      Intradermal injection of louse Ag led to immediate and late phase responses in
      the infested lambs while the naive lambs showed only minimal responses. Levels of
      dermal MHC II(+), CD1b(+), T19(+)and IgE(+) cells, eosinophils and diffuse IgE
      staining in infested lambs following injection of louse Ag were similar to or
      exceeded those in untreated skin and, with few exceptions, were higher than in
      naive lambs. Additionally, cytokine gene expression of IL-4, IL-5, IL-13 and IL
      10 increased to peak levels 4 h following Ag injection in the infested lambs (p<
      or =0.001, < or =0.05, < or =0.05 and < or =0.001 respectively compared to
      untreated controls) and remained significantly elevated compared to that observed
      in the naive controls for the duration of the experiment. Significant elevations
      of MHC II(+) cells and IL-4, IL-5, IL-13 and IL-10 gene expression were observed
      in the louse-naive lambs following injection of louse Ag but were much less
      pronounced than in the infested lambs. These results indicated that louse
      infestation in lambs elicited a highly skewed Th2 immuno-inflammatory response
      with many characteristics similar to those seen with other parasitic infections
      and also in atopic dermatitis.

PMID- 19157571
TI  - Quantitative analysis of inflammatory cytokines expression in peripheral blood
      mononuclear cells of the ferret (Mustela putorius furo) using real-time PCR.
AB  - This study describes the expression pattern of cytokines, interferon-gamma (IFN
      gamma), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and IL-10,
      produced by LPS stimulation in peripheral blood mononuclear cells (PBMCs) of the
      ferret (Mustela putorius furo). Real-time PCR was used with TaqMan probes, which
      were modified by dual-labeled probes (TAMRA/FAM), quantitative analysis of
      cytokine mRNA comparing the cytokine with the housekeeping gene, ferret GAPDH, as
      the relative C(t) value. Expression peaks of IFN-gamma, TNF-alpha, IL-6 mRNA
      occurred 2 h after LPS stimulation, whereas the IL-10 peak was 8 h post-LPS. In
      the present study, peak cytokine expression was detected within 8 h, similar to
      several other mammalian studies. This current study provides baseline information
      on inflammatory cytokines of ferret PBMCs.

PMID- 19157572
TI  - Elevated immune response in the brain of autistic patients.
AB  - This study determined immune activities in the brain of ASD patients and matched
      normal subjects by examining cytokines in the brain tissue. Our results showed
      that proinflammatory cytokines (TNF-alpha, IL-6 and GM-CSF), Th1 cytokine (IFN
      gamma) and chemokine (IL-8) were significantly increased in the brains of ASD
      patients compared with the controls. However the Th2 cytokines (IL-4, IL-5 and IL
      10) showed no significant difference. The Th1/Th2 ratio was also significantly
      increased in ASD patients. CONCLUSION: ASD patients displayed an increased innate
      and adaptive immune response through the Th1 pathway, suggesting that localized
      brain inflammation and autoimmune disorder may be involved in the pathogenesis of
      ASD.

PMID- 19157573
TI  - Distal esophageal foreign bodies: is it a common occurrence post-fundoplication
      requiring immediate intervention?
AB  - OBJECTIVE: Dysphagia secondary to "tight" distal esophageal wraps are a well
      known complication of Nissen fundoplication (NF). However, the literature makes
      no mention of distal esophageal foreign bodies (DEFB) appearing after NF. This
      study was undertaken to determine the occurrence of asymptomatic DEFB in children
      post-fundoplication. METHODS: A retrospective review and case series of
      radiographic images of children who underwent NF between 2001 and 2004. Images
      reviewed include chest and abdominal radiographs, esophagrams, and oropharyngeal
      motility studies. MAIN OUTCOME: DEFB on radiology report and image. RESULTS: Two
      hundred and thirty-three children (135 males and 98 females) underwent NF at the
      ages of 15 days to 19.5 years. Two thousand and seven radiographs were reviewed.
      Five FBs (2.15%) were noted. Four of the five FBs (80%, overall incidence 1.72%)
      were present in the distal esophagus. Three required rigid esophagoscopy (one
      marble and one with multiple foreign bodies (FBs) for removal. One who had a
      distal FB seen on barium swallow 'spontaneously passed' during esophagoscopy.
      CONCLUSION: DEFB in children status post-NF is unusual with an incidence 1.72% of
      our patients. Our review might be underestimating the incidence as translucent
      foreign bodies may have been missed. DEFB are surprising due to the fact that
      most of these children are neurologically impaired and gastrostomy-tube fed. The
      children's NPO status may also result in these DEFB remaining asymptomatic until
      being 'incidentally' found on radiographic imaging. Thus, NF may predispose to
      obstruction when a foreign body (FB) is ingested; but because of the population
      involved, this remains a fairly unusual entity. However, the presence of a DEFB
      in this population may necessitate prompt endoscopic retrieval as the likelihood
      of spontaneous passage is less.

PMID- 19157574
TI  - A prospective multi-centre randomised controlled trial comparing PlasmaKnife with
      bipolar dissection tonsillectomy: evaluating an emerging technology.
AB  - OBJECTIVE: To clinically evaluate and compare the PlasmaKnife to bipolar
      electrocautery in paediatric tonsillectomy. METHODS: A prospective, multi
      centred, double-blinded randomised controlled trial, conducted in central London
      teaching hospitals. The participants were 100 patients aged 2-16 years with
      recurrent tonsillitis or obstructive adenotonsillar hypertrophy awaiting a
      tonsillectomy were recruited in to the study. The primary outcome measures were
      throat, ear and swallowing pain scores over two weeks. Secondary outcome measures
      were return to normal diet, return to normal activity, analgesic requirements,
      operation time and intra-operative blood loss. RESULTS: Surgical dissection was
      similar between the two groups with minimal blood loss and comparable overall
      operative times. We found that PlasmaKnife tonsillectomy caused more throat pain
      at 24 h (p=0.02). There was a tendency for a higher proportion in the bipolar
      dissection group to return to a normal diet, at day 3 (p=0.05) and at day 7
      (p=0.04). The bipolar dissection returned to normal activities in a larger
      proportion than the PlasmaKnife group at day 3 (p=0.02) and at day 7 (p=0.01).
      There is some evidence of an association between use of analgesia at day 14 and
      method of tonsillectomy (p=0.03); the PlasmaKnife group tended to use less
      analgesia. During the study, four secondary bleeds occurred in the PlasmaKnife
      group and one in the bipolar dissection group, and all were managed
      conservatively. CONCLUSION: Our study has found no significant advantage to
      PlasmaKnife over bipolar diathermy tonsillectomy. However, this preliminary study
      finds PlasmaKnife to be an interesting instrument and may warrant a larger
      randomised study to evaluate the potential advantages.

PMID- 19157575
TI  - Diagnostic challenges of laryngeal papillomatosis and its implications among
      children in developing country.
AB  - OBJECTIVES: To create an awareness of laryngeal papillomatosis in children and
      the implications of its mismanagement among the general practitioner and
      paediatricians, and to offer suggestions on its diagnostic techniques. METHOD:
      Medical records of children with histologically confirmed laryngeal
      papillomatosis managed at the Otorhinolaryngology department of University
      College Hospital Ibadan Nigeria through 1993-2007 were reviewed for essential
      clinical data. RESULTS: There were 38 paediatric patients, 23 (60.53%) males and
      15 (39.47%) females, with laryngeal papillomatosis. Only 2 (5.26%) of these
      patients were correctly diagnosed by the referring clinicians. Diagnosis was
      delayed for 5 weeks to 3 months. About 90% of these patients had emergency
      tracheostomy and 92% had surgical excision for 2 sections or less. CONCLUSION:
      Laryngeal papillomatosis misdiagnosis and mismanagement were common in our
      environment due to clinicians not being conversant with the disease entity. It
      should therefore be considered an important differential diagnosis in children
      with laryngeal symptoms to improve its clinical outcome. Otorhinolaryngologists
      should always be involved early without delay in the management.

PMID- 19157576
TI  - High frequency of connexin26 (GJB2) mutations associated with nonsyndromic
      hearing loss in the population of Kerala, India.
AB  - OBJECTIVE: Mutations in connexin 26 gene (GJB2) are the most common cause of
      hearing loss in different populations. The aim of our study was to determine the
      prevalence of GJB2 mutations in the population of Kerala, India. METHODS: This
      study was conducted on the genomic DNA of 86 affected subjects and their
      relatives from 59 families of Kerala, India. Mutation detection was done by
      sequencing and PCR-RFLP. RESULTS: 36% of the probands had mutations in the GJB2
      gene. We found that 45% (15/33) of the families that had a family history of
      deafness had mutations in GJB2 gene. Two different mutations were identified.
      W24X mutation was detected in 32.5% of the affected patients. Analysis of control
      samples revealed a carrier frequency of 0.0357 for this mutation. The estimation
      of haplotype frequency revealed that there was a significant association between
      the W24X mutation and the haplotype in this region with respect to the markers,
      D13S143 and D13S175 suggesting a founder effect for this mutation in this
      population. A novel mutation, R32L was detected in 3.5% of the affected patients.
      Structural prediction revealed that this mutation alters the helical structure of
      the first transmembrane domain of GJB2 protein resulting in defective gap
      junctions. CONCLUSION: Mutations in connexin26 is responsible for 36% of non
      syndromic sensorineural deafness in the population of Kerala, India.

PMID- 19157577
TI  - Pediatric tracheostomy in conjoined twins: multidisciplinary approach.
AB  - Tracheostomy for definitive airway management in conjoined twins is a challenge
      for the surgeon, anesthesiologist, and support staff. A carefully choreographed
      multidisciplinary approach is required. A literature search finds few reports on
      tracheostomy in conjoined twins. We report our experience with tracheostomy with
      5.5-month-old conjoined omphalopagus twins who were attached facing each other.
      Initial planning led to a careful rehearsal of infant positioning focused on
      optimizing anterior cervical exposure. A postoperative tracheostomy care plan was
      also addressed. Each twin was assigned his own anesthetic team and equipment
      early in his life to provide consistent care for the anticipated multiple
      surgical procedures throughout his hospital stay. Issues addressed in this report
      include transportation, intubation, intraoperative airway management, the
      mechanical ventilatory pattern of two individuals sharing a common diaphragm, and
      the pharmaceutical management of two children with partially shared vascular
      supply.

PMID- 19157578
TI  - Indications for image-guidance in pediatric sinonasal surgery.
AB  - OBJECTIVES: To determine the indications and safety of image-guidance for
      pediatric sinonasal surgery. METHODS: A retrospective review was carried out of
      all patients undergoing image-guided sinus surgery using a single electromagnetic
      navigation system. All patients less than 18 years who underwent image-guided
      endoscopic sinus surgery over a 5-year period at a tertiary children's hospital
      were included. The means and ranges of age, preoperative setup time, gender
      distribution, and indications for surgery were determined. Operative time,
      anatomic regions explored, and intraoperative complications were also analyzed.
      RESULTS: Thirty-three patients underwent image-guided surgery over a 5-year
      period. The mean age was 12 years, with 23 males and 10 females. Mean operative
      time and preoperative setup time was 128 and 43 min, respectively. Indications
      for surgery included chronic (30.3%) and acute (12.1%) rhinosinusitis,
      nasopharyngeal angiofibroma (9.1%), allergic rhinosinusitis (9.1%) and allergic
      fungal sinusitis (9.1%). CONCLUSIONS: This series represents the largest
      collection of pediatric image-guided sinus surgery. In our population, image
      guidance was only used for advanced sinonasal procedures where there was an
      anatomic abnormality or disease that extended to the sphenoid sinus, frontal
      sinus, orbit, or skull base. No complications were noted.

PMID- 19157579
TI  - Effects of the synthetic estrogen, 17alpha-ethinylestradiol, on aggression and
      courtship behavior in male zebrafish (Danio rerio).
AB  - The synthetic estrogen, 17alpha-ethinylestradiol (EE(2)), is the active component
      in oral contraceptive pills. It is excreted from the human body in high amounts
      and released via sewage treatment plant effluent into aquatic environments. In
      fish, estrogen receptors have strong binding affinities for EE(2), and exposure
      raises the possibility of adverse neuroendocrine responses in aquatic animals. In
      the present study we explored the effects of dissolved-phase EE(2) on the
      dynamics of male-male aggression and courtship behaviors in adult zebrafish.
      Further, we assessed whether the behavioral effects of EE(2) result in changes in
      male offspring paternity. We scored the aggressive behaviors of individual
      unexposed males and categorized these fish as either dominant or subordinate. We
      then exposed dominant males to EE(2) at doses of 0, 0.5, 5.0, and 50.0ng/L for
      48h. Subsequent trials examined the agonistic behaviors of males in two testing
      scenarios: (1) a dyadic encounter with another male alone, and (2) a competitive
      spawning interaction with another male and three adult females. Competitive
      spawning tests were also used to assess the impacts of EE(2) exposure on
      courtship behavior and paternity using males that were homozygous for green
      fluorescent protein (GFP) expression under the control of the islet-1 promoter.
      We found that EE(2) at all exposure concentrations reduced male aggression during
      male-male dyadic encounters and caused a social dominance reversal in 50% of the
      fish at the highest exposure dose (50ng/L EE(2)). The frequency of courtship
      specific behavior decreased in dominant males exposed to the steroid, though this
      effect was only significant for the lowest dose group (0.5ng/L EE(2)). In the
      highest exposure group (50ng/L EE(2)), 50% of dominant males relinquished
      paternal dominance. Our results show that short-term exposure to EE(2) at
      environmentally relevant levels can alter aggression, and shift individual social
      status and reproductive success in male zebrafish.

PMID- 19157580
TI  - Particulate and soluble hexavalent chromium are cytotoxic and genotoxic to
      Steller sea lion lung cells.
AB  - Hexavalent chromium is an environmental contaminant. Within the environment,
      marine waters are a common site for hexavalent chromium deposition. We have
      recently reported significantly high levels of chromium in skin tissue from North
      Atlantic right whales. These findings demonstrate that marine species are being
      exposed to chromium. It is possible that such exposures may be playing a role in
      population declines evident among certain marine mammals, such as the Steller sea
      lion. We developed a Steller sea lion lung cell line from Steller sea lion lung
      tissue. Hexavalent chromium was cytotoxic to these primary lung fibroblasts as 1,
      2.5, 5, 10 and 25microM sodium chromate induced 104, 99, 92, 58 and 11% relative
      survival, respectively. It was also genotoxic as 0, 1, 2.5, 5 and 10microM sodium
      chromate damaged chromosomes in 6, 11, 21, 36, and 39% of metaphases and damaged
      6, 12, 27, 49 and 57 total aberrations in 100 metaphases, respectively. We also
      considered the toxicity of particulate hexavalent chromium, as it is the more
      potent carcinogen in humans. We found that 0.1, 0.5, 1, 5 and 10microg/cm(2)
      particulate chromate induced 95, 88, 91, 70, and 52% relative cell survival,
      respectively. These concentrations were genotoxic and damaged chromosomes in 9,
      13, 18, and 23% of metaphases and induced 9, 15, 20 and 30 total aberrations per
      100 metaphases, respectively. These data indicate that if sufficiently exposed,
      chromium may adversely affect the struggling Steller sea lion population. It
      would be prudent to investigate the effects chromium has in other Steller sea
      lion organs in order to derive a better understanding of how chromium in the
      marine environment may be affecting the declining Steller sea lion population.

PMID- 19157581
TI  - Quality of life (QOL) axiological profile of the elderly population served by the
      Family Health Program (FHP) in Brazil.
AB  - With the purpose of optimizing the satisfaction of the elderly subjects, either
      existential or not, presenting their unique preference, this research aimed to
      evaluate the effects of aging on QOL of the aged persons, served by the FHP. The
      basic intention was to establish parameters of QOL-impact on aging. Our sample
      was a non-selected population of aged volunteers from Pereque-Mirim-I Family
      Health Unity, in Caraguatatuba, Sao Paulo, Brazil. In this correlational
      descriptive research, the elderly subjects answered a questionnaire on QOL,
      specific to the aged persons (WHOQOL-OLD). These answers revealed the degree to
      which of the six facets of WHOQOL-OLD was given priority. The dimensional
      techniques of descriptive statistics (mean+/-S.D., median, coefficient of
      variation) normality evaluation (Kolmogorov-Smirnov), and inferential statistical
      techniques (Z-score test, chi2) were adopted, considering the level-II error=10%
      and accepting level-I error=5%. The main results revealed a correlation between
      the income and QOL. Death and dying appeared to be a substantial preoccupation,
      opposed to intimacy that raised the QOL level. It is suggested that any works
      directed to the elderly population should take in consideration the self
      evaluation of aging effects on QOL.

PMID- 19157582
TI  - Bundle branch block and other cardiovascular disease risk factors: US-Japan
      comparison.

PMID- 19157583
TI  - Functional estrogen receptor alpha promoter polymorphism is associated with
      improved endothelial-dependent vasolidation.
AB  - Estrogen receptor alpha (ERalpha) mediates beneficial actions on endothelial
      nitric oxide synthase (eNOS) and cholesterol metabolism. Genetic variations in
      the promoter of the ERalpha may therefore influence vascular function. We have
      identified a single nucleotide polymorphism (T>C) in the transcriptional element
      "ERNE" upstream of ERalpha which abolished the negative effect of this element in
      luciferase reporter assays and was associated with reduction in LDL cholesterol
      in a small association study. We have now examined for the association of this
      putative functional polymorphism with endothelial function. Endothelial-dependent
      relaxation (EDR) was measured in organ bath preparations of human saphenous vein
      obtained from 101 individuals (81 males and 20 females) undergoing coronary
      artery bypass surgery. The presence of the variant C allele was associated with
      enhanced EDR independently of hypercholesterolaemia, smoking and diabetes, as
      well as sex (ANOVA for ACh induced relaxation: p=0.033). In males, the presence
      of the C allele was associated with a 225% augmentation of endothelial-dependent
      relaxation compared to wild-type (55.5+/-10%; n=3 vs. 24.7+/-1%; n=78; p<0.001).
      In summary, a polymorphism in the ERalpha negative transcriptional element which
      results in increased transcription in vitro is associated with substantial
      augmentation of endothelial-dependent vasorelaxation.

PMID- 19157584
TI  - Difference in resource utilization between patients with acute and chronic heart
      failure from Japanese administrative database.
AB  - BACKGROUND: Many studies have reported economic evaluation of evolving agents or
      therapies for patients with heart failure (HF). However, little is known whether
      the disease progression category (acute or chronic HF) would be considered as a
      risk adjustment in health service research. OBJECTIVES: This study profiles the
      difference in resource use or medical care for acute versus chronic HF. METHODS:
      This study analyzed 17,912 HF patients treated in 62 academic hospitals and 351
      community hospitals. Study variables included demographic variables, comorbid
      status, physical activity or disease progression at admission, procedures and
      laboratory tests, type and dose of heart-related medications, length of stay
      (LOS), and total charges (TC; 1 US$= 100 yen) for acute and chronic HF. The
      independent contributions of disease progression categories on LOS and TC were
      identified using multivariate analysis. RESULTS: We identified 9813 chronic and
      8099 acute HF patients. Median LOS was 18 days for both chronic and acute HF,
      whereas TC was US$5731 and US$6447, respectively. Regression analysis revealed
      that acute HF was associated with a slightly greater TC, whereas performance of
      procedures was the most prominent factor. As NYHA class was the next most
      influential factor, class 3 or 4 resulted in longer LOS or greater TC, than did
      class 1. CONCLUSIONS: This study suggests that acute HF increased resource use
      slightly, whereas use of some practices indicated in critical care was affected
      more by the procedures performed. Disease progression category should remain an
      indicator for appropriateness of medical care.

PMID- 19157585
TI  - Fatty acid metabolism and myocardial perfusion imaging for the evaluation of
      global left ventricular dysfunction following acute myocardial infarction:
      comparisons with echocardiography.
AB  - BACKGROUND: Myocardial fatty acid metabolic imaging with beta-methyl iodophenyl
      pentadecanoic acid (BMIPP) and perfusion imaging with tetrofosmin (TF) combined
      can predict post ischemic salvageable myocardium and persistent left ventricular
      (LV) dysfunction. This study was designed for the first time to assess systolic,
      diastolic and global LV dysfunction considering BMIPP and TF mismatched defect
      score (MMDS), and comparing this approach with the conventional Doppler
      echocardiography. METHODS: Thirty four patients with first acute myocardial
      infarction (AMI) were enrolled, and all of them underwent percutaneous coronary
      intervention (PCI). BMIPP and Tetrofosmin (TF) scans were performed at 7+/-3.5
      days of admission. Echocardiography was performed within 24 h of admission, at an
      interval of 1 and 3 months. MMDS was compared with systolic: ejection fraction
      (EF), wall motion score index (WMSI), fractional shortening (FS); diastolic:
      mitral valve deceleration time (MVDT), E/E', left atrial volume index (LAVI);
      combined systolic and diastolic parameter: left ventricular myocardial
      performance index (LVMPI). RESULTS: A good correlation was observed between BMIPP
      and TF defect score (p<0.00001), and in 31 (91%) patients BMIPP defect score was
      higher than that of TF. The MMDS showed significant correlation with EF (r=-0.64,
      p=<0.00001), WMSI (r=0.61, p<0.0001), and FS(r=-0.65, p<0.00001), LAVI (r=-0.32,
      p<0.05), and LVMPI (r=0.37, p<0.02) during follow up echocardiography at 1 month.
      MVDT and E/E' did not correlate with MMDS. CONCLUSION: Perfusion-metabolism
      mismatched defect score was well correlated with the evolution of global left
      ventricular dysfunction following AMI evidenced from conventional Doppler
      echocardiography.

PMID- 19157586
TI  - The emerging role of percutaneous coronary intervention in the management of
      unprotected left main coronary artery disease: ongoing debate.

PMID- 19157587
TI  - A family of hereditary long QT syndrome caused by Q738X HERG mutation.

PMID- 19157588
TI  - Prostate-specific antigen and acute myocardial infarction: a possible new
      intriguing scenario.
AB  - Prostate-specific antigen (PSA) has been identified as a member of the human
      kallikrein family of serine proteases and it is an established marker for
      detection of prostate cancer. Apparently spurious result has been reported in a
      work about mean serum PSA concentration during acute myocardial infarction with
      mean serum PSA concentration significantly lower on day 2 than either day 1 or
      day 3 and it has been reported that these preliminary results could reflect
      several factors, such as antiinfarctual treatment, reduced physical activity or
      an acute-phase response. Elevation of prostate-specific antigen has also been
      reported during acute myocardial infarction in three patients and in another one
      also after transurethral resection of the prostate (TURP) and without
      histological diagnosis of prostate cancer. In our report we present three cases
      of diminution of serum PSA concentration during acute myocardial infarction. Our
      report extends the evaluation of PSA during acute myocardial infarction. It seems
      that when elevation of prostate-specific antigen occurs during acute myocardial
      infarction, coronary lesions are frequent and often more severe than when
      diminution of prostate-specific antigen occurs during acute myocardial
      infarction. It opens a possible new intriguing scenario of the role of the
      prostate-specific antigen in acute myocardial infarction.

PMID- 19157589
TI  - ACE-inhibitor therapy and survival among patients with multiorgan dysfunction
      syndrome (MODS) of cardiac and non-cardiac origin.
AB  - BACKGROUND: The multiple organ dysfunction syndrome (MODS) is the sequential
      failure of organ systems after a trigger event (e.g. cardiogenic shock) with a
      high mortality. ACE-inhibitors [ACEI] are known to ameliorate depressed autonomic
      function (heart rate variability [HRV]) to improve endothelial function and to
      decrease blood pressure. Modifications of these targets reduce major adverse
      cardiovascular events (patients with arterial hypertension, coronary artery
      disease and chronic heart failure). Our study aimed to characterize potential
      benefits of ACEI therapy in MODS patients. METHODS: 178 score-defined consecutive
      patients were enrolled. Inclusion criterion was an APACHE II score >or=20 at
      admission to the ICU. Patients were evaluated for ACEI therapy and followed for
      28, 180 and 365 days. HRV was calculated according to the international
      standards. RESULTS: 68 patients received an ACEI during their ICU stay whereas
      110 did not. The 28-day mortality was 55% (no ACEI treatment) vs. 22% (ACEI
      treatment, p<0.0001) and the 1-year mortality accounted for 75% (no ACEI) vs. 50%
      (ACEI), p<0.0001. There was no significant survival difference between early and
      later application of ACEI (after day 4), both application modes were
      characterized by an improved survival. MODS patients with ACEI treatment at
      admission had a better preserved HRV. CONCLUSIONS: Our results may suggest that
      MODS patients with ACEI treatment may have lower short- and longer-term
      mortality. HRV was less attenuated when patients received ACEI therapy at
      admission. Consequently, effectiveness of ACEI therapy should be validated in a
      prospective trial.

PMID- 19157590
TI  - Asymptomatic hypoxia in a young pregnant lady--unusual presentation of atrial
      septal defect.
AB  - Atrial septal defect (ASD) accounts for approximately a third of all congenital
      heart disease in adults. It is rarely diagnosed and less likely to cause any
      symptoms during infancy, but approximately more than half become symptomatic
      around their fifth decade. In clinical setting it commonly presents as exertional
      dyspnoea, atrial arrhythmias, right heart failure and is rarely related to the
      thromboembolic complications due to paradoxical embolism. ASD is usually well
      tolerated in pregnancy with low risk of miscarriages, stillbirth, preterm
      delivery and perinatal mortality. We report an interesting case of undiagnosed
      large ostium secundum atrial septal defect in a young pregnant lady presented as
      'asymptomatic hypoxia'. All pregnant women with hypoxia either pre or post-partum
      should be investigated to rule out any undiagnosed intra cardiac shunts to
      minimise maternal and foetal complications.

PMID- 19157591
TI  - Does preoperative tethering symmetry affect left ventricular reverse remodeling
      after restrictive annuloplasty?
AB  - BACKGROUND: We hypothesized that a preoperative symmetric pattern with anterior
      mitral leaflet (AML) tethering predominance is related to lack of LVRR after
      restrictive annuloplasty. METHODS: In 300 patients with surgical annuloplasty for
      chronic ischemic mitral regurgitation the AML and posterior mitral leaflet (PML)
      tethering angles were quantified and patients were divided on the basis of the
      preoperative anterior/posterior tethering angle ratio: there were 144 patients
      with symmetric (Group 1) and 156 with asymmetric (Group 2) preoperative tethering
      pattern patients underwent echocardiography preoperatively, at discharge and at
      follow-up appointments (6 months [IQR 5-8 months]; late, 48 months [15-63
      months]). Reverse remodeling was defined as a reduction in left ventricular end
      systolic volume index >15%. RESULTS: LVRR was higher in the asymmetric group at
      discharge (69.2% vs. 9.7%, p<0.001), early (70.55% vs. 10.45%, p<0.001 and late
      follow up (81.4% vs. 4.8%, p<0.001). At multivariable regression analysis
      corrected by significant key factors of LVRR, symmetric leaflet tethering (OR,
      4.8 [95% CI 2.9-5.6], p<0.001), anterior tethering angle alpha'<39.5 degrees (OR,
      5.0 [95% CI 2.0-6.6], p<0.001), coaptation height<11 mm (OR, 2.5 [95% CI 1.1
      3.3], p=0.006) and coaptation length > or =8 mm at the end of procedure (OR, 2.0
      [CI 0.8-3.0], p=0.01) were independent predictors of LVRR. Compared with patients
      with asymmetric pattern (adjusted OR 0.2 [95% CI 0.03-1.6), those with symmetric
      pattern had >4-fold odds for lack of LVRR. CONCLUSIONS: The preoperative
      symmetric pattern with AML prevalence was strongly associated with lack of
      reverse remodeling after annuloplasty. An accurate echocardiographic evaluation
      of the tethering mechanisms should be incorporated into clinical risk assessment
      and prediction models.

PMID- 19157592
TI  - Patent foramen ovale in carcinoid heart disease.
AB  - Carcinoid heart disease (CHD) is an uncommon valvular heart disease that may
      occur in the case of carcinoid syndrome, due to the release of serotonin. Right
      sided CHD is more frequent than left-sided CHD because of inactivation of
      serotonin by the lung. We report the case of a 74-year-old woman who had a
      previous history of digestive endocrine tumor and carcinoid syndrome, presented
      with a significant progression of its valvular heart disease during a follow-up
      of 1 year. A severe shunt through a patent foramen ovale (PFO) was observed and
      was associated with the development of left-sided CHD. We performed percutaneous
      closure of PFO, with a reduction of symptoms. Our report highlights that
      assessment of PFO in patient with carcinoid syndrome is of importance because it
      allows to detect patient at high risk of CHD progression and percutaneous PFO
      closure may thus be proposed.

PMID- 19157593
TI  - Standard Deviation of normal interbeat intervals as a risk marker in patients
      with left ventricular systolic dysfunction: a meta-analysis.
AB  - Our aim was to evaluate the Standard Deviation of Normal-Normal (SDNN) interbeat
      interval as a risk marker in left ventricular systolic dysfunction (LVSD)
      patients through a meta-analysis. We searched PubMed for studies that evaluated
      SDNN as a predictor of all-cause-death, cardiac death, transplantation, and
      progressive clinical deterioration using a search strategy validated for MEDLINE.
      Mean values and SD for SDNN in sixteen studies included were 115+/-48 ms in
      survivors versus 87+/-40 ms in non-survivors, resulting in a statistically
      significant standardized mean difference (0.594, 95%CI 0.385 to 0.803). In
      conclusion, SDNN may be a useful prognostic marker in LVSD. Additional studies
      must evaluate if SDNN may be used to subsidize therapeutic decisions.

PMID- 19157594
TI  - A case of very late stent thrombosis facilitated by drug eluting stent fracture:
      comparative images before and after stent fracture detected by 64-multidetector
      computed tomography.
AB  - A stent fracture (SF) is one of the responsible factors for in-stent restenosis
      after a percutaneous coronary intervention. Factors that have an important role
      for a SF are vessel tortuosity, the presence of a right coronary artery lesion,
      overlapping stents, and the use of a drugeluting stent (DES) such as a sirolimus
      eluting stent. Unlike with the use of bare metal stents, most SFs have occurred
      with the use of DES, and a DES may be a possible factor for a SF. A SF can cause
      clinical problems that range from stable angina to acute coronary syndrome. We
      experienced a case of acute myocardial infarction that was combined with a SF. We
      describe here the coronary angiography findings and the 64-multidetector computed
      tomography images before and after the SF.

PMID- 19157595
TI  - Time-dependent dynamic mobilization of circulating progenitor cells during
      percutaneous coronary intervention in diabetics.
AB  - BACKGROUND: Circulating progenitor cells (CPC) especially endothelial progenitor
      cell (EPC) levels and functions are attenuated in diabetic patients. This may
      explain the poorer outcome of diabetics undergoing percutaneous coronary
      intervention (PCI). We aim to study the dynamic changes of these cells in these
      patients. METHODS: Blood of 8 diabetics with stable coronary artery disease who
      underwent elective PCI, were obtained at baseline, 1, 4 and 24 h after PCI.
      Fluorescence activated cell sorting (FACS) analysis was performed to quantitate
      CD34+ and CD34+/ KDR+ cells. Patients with recent acute coronary syndrome were
      excluded. RESULTS: After PCI, decreases in CPC from baseline were detected in 7
      out of the 8 patients. In these 7 patients, mean CD34+ and CD34+/KDR+ cells were
      182+/-99/1 x 10(5) and 18+/-16/1 x 10(5) cells respectively. Maximal decrease of
      CD34+ and CD34+/KDR+ cells were 47.8% and 53.3% at 1 h and 4 h respectively. At
      24 h, CPC levels returned to baseline but were not elevated. The only patient
      with raised cardiac enzymes has instead, 2 to 3 fold increase in CPCs at 1 and 4
      h. CONCLUSIONS: We found a transient dip in circulating progenitors early during
      PCI. This suggests incorporation of the cells into the sites of vascular
      denudation. The absence of subsequent CPC elevation post-PCI in diabetes may be
      associated with known poorer outcome of these patients. With myocardial injury,
      more progenitors may be mobilized from the bone marrow into the circulation and
      abolish the hyperacute reduction in circulating levels.

PMID- 19157596
TI  - The "mirror" papillary muscle.
AB  - Various structural anomalies of the papillary muscles have been described in a
      variety of primary and secondary cardiovascular disorders. Some of these lead to
      intraventricular pressure gradients, while some has no obvious functional
      consequences at present. A peculiar anterolateral papillary muscle anomaly with
      an accessory papillary muscle, causing the appearance of a mirror image on
      transthoracic echocardiography is described.

PMID- 19157597
TI  - Left hemothorax: a presentation of a late ventricular perforation caused by an
      active fixation pacing lead.
AB  - Ventricular perforation, late after ventricular lead placement at the right
      ventricular apex is rare, and though, commonly presents with chest pain, loss of
      pacing and/or sensing, and hemodynamic instability caused by cardiac tamponade,
      it can rarely cause left sided hemothorax needing surgical exploration.

PMID- 19157598
TI  - Uric acid levels for the prediction of prognosis in patients with acute ST
      elevation myocardial infarction: a new potential biomarker.

PMID- 19157599
TI  - The Brugada syndrome: the perfect storm of genetics and environment?

PMID- 19157600
TI  - Left atrial intramural hematoma after percutaneous coronary intervention.
AB  - We described a complication during percutaneous coronary intervention. A bleeding
      into the left atrial wall occurred after stenting of the right coronary artery.
      Echocardiography revealed the diagnosis of a left atrial intramural hematoma.
      Conservative treatment was performed. After 4 weeks the hematoma resolved
      completely. Left atrial intramural hematoma as a complication after percutaneous
      coronary intervention has not been reported in the literature yet.

PMID- 19157601
TI  - Full recovery of Takotsubo cardiomyopathy (apical ballooning) in two days.
AB  - Takotsubo cardiomyopathy (TTC) is a new clinical entity characterised by acute
      but rapidly reversible left ventricular systolic dysfunction. This case report
      demonstrates the unique finding of a complete normalization of left ventricular
      function in a patient with TTC in only 36 h documented by cardiac magnetic
      resonance imaging. To our best knowledge, this is the most rapid complete
      recovery of left ventricular apical ballooning reported, yet. Medical management
      of our patient included optimized antihypertensive therapy with intravenous
      administration of the alpha-1-adrenergic blocker urapidil and the beta-blocker
      bisoprolol in highest recommended doses. Although optimal management of TTC has
      not been established, alpha- and beta-blockade may be beneficial for rapid
      recovery of TTC and may be protective against the recurrence of stress-related
      left ventricular dysfunction due to acute and sudden catecholamine excess.

PMID- 19157602
TI  - Brain natriuretic peptide as an integrator of cardiovascular stiffening in
      hypertension.
AB  - BACKGROUND: Left ventricular (LV) diastolic dysfunction and impairment of aortic
      elastic properties represent common sequelae of hypertension. We investigated the
      relationships of these cardiovascular adaptations with brain natriuretic peptide
      (BNP) levels in newly-diagnosed hypertension. METHODS: 200 consecutive
      hypertensives without LV hypertrophy (aged 52 years, 134 males, office
      BP=151.4/95.5 mmHg) underwent 24 hour ambulatory BP measurement as well as aortic
      stiffness and LV diastolic function assessment by means of carotid-femoral pulse
      wave velocity (c-f PWV) measurement and Tissue Doppler Imaging (TDI),
      respectively. Based on BNP values patients were classified into tertiles.
      RESULTS: Hypertensives in the highest, compared to those in the lowest BNP
      tertile had significantly higher 24 h pulse pressure (by 6.2 mmHg, p=0.002),
      lower 24 h diastolic BP (by 5.7 mmHg, p=0.014), decreased Em/Am ratio (by 0.09,
      p=0.048) and increased c-f PWV (by 0.7 m/s, p=0.042). Moreover, hypertensives in
      the highest, compared with those in the lowest and the medium tertile of BNP,
      exhibited significantly lower Em (by 1.2 cm/s, p=0.001 and 1 cm/s, p=0.004,
      respectively) and higher E/Em ratio (by 1.3, p=0.018 and 1.3, p=0.014,
      respectively). BNP was significantly associated with E/Em ratio, 24 h pulse
      pressure and c-f PWV independently from age. CONCLUSION: In hypertensives plasma
      BNP levels are associated not only with LV diastolic dysfunction but also with
      aortic stiffening. These findings suggest that BNP even within normal range
      constitutes a surrogate for cardiovascular functional impairment in the setting
      of essential hypertension without LV hypertrophy.

PMID- 19157603
TI  - Multimarker strategy for the prediction of 31 days cardiac death in patients with
      acutely decompensated chronic heart failure.
AB  - BACKGROUND: To investigate the combined prognostic value of admission serum
      levels of B-type natriuretic peptide (BNP), cardiac troponin I (cTnI) and high
      sensitivity C-reactive protein (hs-CRP), in patients hospitalized because of
      acutely decompensated severe (New York Heart Association class III/IV) low-output
      chronic heart failure (CHF). METHODS: A total of 577 consecutive patients
      recruited in the 5 participating centers, were studied. Cardiac mortality by 31
      days was the prespecified primary study end point. RESULTS: A total of 102
      (17.7%) patients died by 31 days. When the study patients were divided according
      to the number of elevated study biomarkers, there was a significant gradual
      increased risk of 31-day cardiac death with increasing in the number of elevated
      biomarkers (p<0.001). The value of the discriminant C statistic for the Cox
      regression analysis, increased significantly when each of the study biomarkers
      was incorporated with the other risk predictors into a Cox regression model, with
      the highest C statistic value for the Cox regression model that included all the
      study biomarkers (p<0.001). By multivariate Cox regression analysis, elevated
      serum levels of BNP (p=0.002), cTnI (p<0.001) and hs-CRP (p=0.02) were
      independent predictors of the study end point. CONCLUSIONS: In conclusion, in
      patients hospitalized for acute decompensation of severe (NYHA III/IV) low-output
      CHF, BNP, cTnI and hs-CRP upon admission offers enhanced early risk
      stratification. With increasing number of elevated biomarkers, the risk of 31-day
      cardiac death increases gradually that implies treatment intensification, and
      closer follow-up.

PMID- 19157604
TI  - Integrated area of desaturation index in patients with myocardial infarction.

PMID- 19157605
TI  - Neopterin - marker of coronary artery disease activity or extension in patients
      with chronic stable angina?

PMID- 19157606
TI  - Cardiac diseases in sarcoglycanopathies.

PMID- 19157607
TI  - Repair of massive ventricular septal defect with tricuspid straddling under mild
      hypothermia cardiopulmonary bypass with beating heart.
AB  - A 17-year-old woman with ventricular septal defect and tricuspid straddling
      valve. There are few reports about these associations in literature. We
      successfully performed a total correction which consisted of a close of the
      ventricular septal defect and suspension of straddling tricuspid valve.
      Ventricular septal defect was closed with a dacron patch and straddling tricuspid
      valve was suspended into the appropriate ventricle. The postoperative course has
      been uneventful.

PMID- 19157608
TI  - Motorcycle helmets and traffic safety.
AB  - Between 1997 and 2005, the number of annual motorcyclist fatalities doubled.
      Motorcyclist fatalities now account for over 10 percent of all traffic-related
      fatalities. However, over the last three decades, states have generally been
      eliminating laws that require helmet use among all motorcyclists. This study
      examines the effectiveness of helmet use and state laws that mandate helmet use
      in reducing motorcyclist fatalities. Within-vehicle comparisons among two-rider
      motorcycles indicate that helmet use reduces fatality risk by 34 percent. State
      laws requiring helmet use appear to reduce motorcyclist fatalities by 27 percent.
      Fatality reductions of this magnitude suggest that the health benefits of helmet
      use laws are not meaningfully compromised by compensating increases in risk
      taking by motorcyclists.

PMID- 19157609
TI  - Volumetric modulated arc radiotherapy for carcinomas of the oro-pharynx, hypo
      pharynx and larynx: a treatment planning comparison with fixed field IMRT.
AB  - PURPOSE: A planning study was performed to evaluate the performance of volumetric
      modulated arc radiotherapy on head and neck cancer patients. Conventional fixed
      field IMRT was used as a benchmark. METHODS AND MATERIALS: CT datasets of 29
      patients with squamous cell carcinoma of the oro-pharynx, hypo-pharynx and larynx
      were included. Plans for fixed beam IMRT, single (RA1) and double (RA2) modulated
      arcs with the RapidArc technique were optimised. Dose prescription was set to 66
      Gy to the primary tumour (at 2.2 Gy/fraction), 60 Gy to intermediate-risk nodes
      and 54 Gy to low-risk nodal levels. The planning objectives for PTV were minimum
      dose >95%, and maximum dose <107%. Maximum dose to spinal cord was limited to 46
      Gy, maximum to brain stem to 50 Gy. For parotids, mean dose <26 Gy (or median <30
      Gy) was assumed as the objective. The MU and delivery time were scored to measure
      expected treatment efficiency. RESULTS: Target coverage and homogeneity results
      improved with RA2 plans compared to both RA1 and IMRT. All the techniques
      fulfilled the objectives on maximum dose, while small deviations were observed on
      minimum dose for PTV. The conformity index (CI(95%)) was 1.7+/-0.2 for all the
      three techniques. RA2 allowed a reduction of D(2%) to spinal cord of
      approximately 3 Gy compared to IMRT (RA1 D(2%) increased it of approximately 1
      Gy). On brain stem, D(2%) was reduced from 12 Gy (RA1 vs. IMRT) to 13.5 Gy (RA2
      vs. IMRT). The mean dose to ipsi-lateral parotids was reduced from 40 Gy (IMRT)
      to 36.2 Gy (RA1) and 34.4 Gy (RA2). The mean dose to the contra-lateral gland
      ranged from 32.6 Gy (IMRT) to 30.9 Gy (RA1) and 28.2 Gy (RA2). CONCLUSION:
      RapidArc was investigated for head and neck cancer. RA1 and RA2 showed some
      improvements in organs at risk and healthy tissue sparing, while only RA2 offered
      improved target coverage with respect to conventional IMRT.

PMID- 19157610
TI  - Modeling the survival of Escherichia coli O157:H7, Listeria monocytogenes, and
      Salmonella Typhimurium during fermentation, drying, and storage of soudjouk-style
      fermented sausage.
AB  - This study quantified and modeled the survival of Escherichia coli O157:H7,
      Listeria monocytogenes and Salmonella Typhimurium in soudjouk-style fermented
      sausage during fermentation, drying, and storage. Batter prepared from ground
      beef (20% fat), seasonings, starter culture, and dextrose was separately
      inoculated with a multi-strain mixture of each pathogen to an initial inoculum of
      ca. 6.5 log(10) CFU/g in the batter. The sausages were subsequently fermented at
      24 degrees C with a relative humidity (RH) of 90% to 95% for 3 to 5 days to ca.
      pH 5.2, pH 4.9 or pH 4.6, then dried at 22 degrees C to a(w) 0.92, a(w) 0.89, or
      a(w) 0.86, respectively, and then stored at 4, 21, or 30 degrees C for up to 60
      days. Lethality of the three pathogens was modeled as a function of pH, a(w)
      and/or storage temperature. During fermentation to pH 5.2 to pH 4.6, cell
      reductions ranged from 0 to 0.9 log(10) CFU/g for E. coli O157:H7, 0.1 to 0.5
      log(10) CFU/g for L. monocytogenes, and 0 to 2.2 log(10) CFU/g for S.
      Typhimurium. Subsequent drying of sausages of pH 5.2 to pH 4.6 at 22 degrees C
      with 80% to 85% RH for 3 to 7 days to a(w) of 0.92 to a(w) 0.86 resulted in
      additional reductions that ranged from 0 to 3.5 log(10) CFU/g for E. coli
      O157:H7, 0 to 0.4 log(10) CFU/g for L. monocytogenes, and 0.3 to 2.4 log(10)
      CFU/g for S. Typhimurium. During storage at 4, 21, or 30 degrees C the reduction
      rates of the three pathogens were generally higher (p<0.05) in sausages with
      lower pH and lower a(w) that were stored at higher temperatures. Polynomial
      equations were developed to describe the inactivation of the three pathogens
      during fermentation, drying, and storage. The applicability of the resulting
      models for fermented sausage was evaluated by comparing model predictions with
      published data. Pathogen reductions estimated by the models for E. coli O157:H7
      and S. Typhimurium were comparable to 67% and 73% of published data,
      respectively. Due to limited published data for L. monocytogenes, the models for
      L. monocytogenes would need additional validations. Results of pathogen
      reductions from this study may be used as a reference to assist manufacturers of
      soudjouk-style sausages to adopt manufacturing processes that meet the regulatory
      requirements. The resulting models may also be used for estimating the survival
      of E. coli O157:H7 and S. Typhimurium in other similar fermented sausage during
      fermentation and storage.

PMID- 19157611
TI  - Monitoring Lactobacillus plantarum BCC 9546 starter culture during fermentation
      of Nham, a traditional Thai pork sausage.
AB  - The use of Lactobacillus plantarum BCC 9546 (LpBCC9546) as a starter culture for
      Nham, a traditional Thai fermented pork sausage ensures product quality and
      consistency. However, no direct evidence has confirmed the growth of this starter
      during Nham fermentation. In order to investigate its role during Nham
      fermentation, LpBCC9546 was genetically modified to distinguish it from the
      natural microflora in Nham. LpBCC9546 was transformed with a recombinant plasmid
      pRV85 to produce the recombinant strain LpG11, which is resistant to erythromycin
      and emits green fluorescence. LpG11 was used as a starter culture for Nham
      fermentation, and its growth was monitored by plating on a selective medium and
      assay of fluorescent activity. During Nham fermentation the numbers of LpG11
      increased ten fold during the first 12 h of fermentation, reaching maximum
      numbers of between 10(7) and 10(8) cfu g(-1) after 24 h, and then declining after
      60 h to 10(5) cfu g(-1) at 168 h. The growth of LpG11 starter culture during Nham
      fermentation was very similar to that of the untransformed LpBCC9546, although
      after a prolonged period of fermentation the recombinant LpG11 bacteria appeared
      to lose the plasmid, or were outgrown by naturally present L. plantarum. The
      acidity, texture and color of fermented Nham inoculated with recombinant LpG11 or
      untransformed LpBCC9546 were similar. These results indicated that the
      recombinant L. plantarum strain LpG11 is a suitable starter culture for Nham
      fermentation, and that the ability to monitor its growth directly during Nham
      fermentation could be exploited to further improve Nham production.

PMID- 19157612
TI  - Fate of acid-resistant and non-acid resistant Shiga toxin-producing Escherichia
      coli strains in experimentally contaminated French fermented raw meat sausages.
AB  - Both pathogenic and nonpathogenic E. coli exhibit a stress response to sublethal
      environmental stresses. Several studies have reported acid tolerance and survival
      characteristics of E. coli O157:H7 in foodstuffs, but there are few reports about
      the tolerance of non-O157 serogroups (STEC) to organic acids in foods. The
      purpose of this study was to examine the effect of the manufacturing process of
      French fermented raw meat sausages on the growth and survival of acid-resistant
      (AR) and non-acid resistant (NAR) STEC strains. The six strains, 3 AR and 3 NAR,
      were inoculated separately into raw sausage mixture at a level of 10(4)-10(5)
      CFU/g. A total of 19 batches of sausages were manufactured. A rapid and similar
      decrease in the number of both AR and NAR STEC strains, from less than 1 to 1.5
      log(10) CFU/g, was observed during the first 5 days of fermentation at 20-24
      degrees C. This rapid decrease was followed by a more gradual but continuous
      decrease in STEC counts after drying at 13-14 degrees C, up to day 35. The STEC
      counts were <10 CFU/g after 35 days for the NAR strains and the same
      concentration for the AR strains on the best before date (day 60). It was not
      possible to detect any NAR STEC after 60 days. The present study shows that the
      process used in the manufacture of French sausages results in a complete
      destruction of NAR STEC strains after 60 days, but it does not have the same
      effect on the AR STEC strains.

PMID- 19157613
TI  - Modelling the effect of the starter culture on the growth of Staphylococcus
      aureus in milk.
AB  - The competitive growth of a starter culture of lactic acid bacteria (Fresco 1010,
      Chr. Hansen, Horsholm, Denmark) and Staphylococcus aureus was studied in milk.
      The lactic bacteria (LAB) were able to induce an early stationary state in S.
      aureus. The developed model highlights that the growth of S. aureus is inhibited
      when the LAB have reached a critical density. The model was tested in different
      conditions of temperature (from 12 degrees to 25 degrees C), for various inoculum
      sizes of LAB and S. aureus. The results show that the model accurately quantifies
      the kinetics of S. aureus as a function of the starter culture.

PMID- 19157614
TI  - Genetic diversity and biofilm formation of Staphylococcus equorum isolated from
      naturally fermented sausages and their manufacturing environment.
AB  - S. equorum is often isolated from naturally fermented sausages and from the
      environment of processing units. The aim of this work was first to characterize
      the genetic diversity of this species in a single small processing unit
      manufacturing traditional sausages without the use of starter cultures. One
      hundred and eighteen S. equorum isolates were collected from meat products and
      surfaces of this unit. Secondly, the capacity to form biofilm of 57 isolates of
      S. equorum selected from pulsed-field gel electrophoresis (PFGE) profiles was
      assessed to determine if this property conferred an advantage for the
      colonization of surfaces in the processing unit. Characterization of the isolates
      by PFGE analysis revealed a high diversity of the strains with 52 distinct PFGE
      patterns detected in this limited environment. It showed also that the exchanges
      between meat products and environmental surfaces could be limited or that the
      strains could be adapted to a specific niche as only four strains out of the 52
      identified colonized both niches. The majority of the S. equorum strains formed
      biofilm; this was determined using a validated test on polystyrene microplates.
      This ability was not correlated with their origin, meat products or environmental
      surfaces.

PMID- 19157615
TI  - Influence of type of microorganism, food ingredients and food properties on high
      pressure carbon dioxide inactivation of microorganisms.
AB  - High pressure carbon dioxide (HPCD) treatment is currently considered as an
      attractive non-thermal process for preserving food. Industrial application of
      this technique requires, among others, systematic (quantitative) data on the
      inactivation of food relevant pathogenic and spoilage microorganisms, and in
      depth information on the effect that the composition and the properties of a food
      matrix have on the inactivation efficacy. The first objective of this study,
      therefore, is to evaluate and compare the HPCD susceptibility of several food
      pathogens and spoilage microorganisms under the same treatment conditions. In the
      second part, the influence of different food components (NaCl, oil, starch, whey
      protein and emulsifier) and food properties (pH, fluid viscosity and water
      activity) on the inactivation efficacy of HPCD was determined. For the first aim,
      a range of Gram-negative and Gram-positive bacteria, yeasts and spores were
      treated with pressurized CO(2) at 10.5 MPa and 35 degrees C during 20 min.
      Bacterial susceptibility towards HPCD treatments followed the sequence Gram
      negative approximately Gram-positive>yeasts>spores and appeared to be related to
      the acid resistance of the organisms. To study the effect of different food
      compounds on HPCD inactivation, the reduction degree of Pseudomonas fluorescens
      was determined in media with and without these components at 10.5 MPa and 35
      degrees C after 5 or 20 min, depending on the tested component. NaCl and the
      emulsifiers Tween 80 and sucrose stearate enhanced bacterial reduction, while oil
      reduced the bactericidal efficacy of HPCD. Starch and whey proteins did not
      influence inactivation. Finally, the influence of pH, fluid viscosity and water
      activity was investigated by determining the reduction of P. fluorescens at 10.5
      MPa and 35 degrees C in suspensions from which the pH, viscosity and water
      activity were adjusted with respectively NaOH or HCl, gelatin or polyethylene
      glycol, and sucrose, NaCl or glycerol. Treatment time depended on the studied
      food property with 5 min for the pH experiments, while other experiments lasted
      20 min. The results indicated that P. fluorescens cells became more sensitive to
      HPCD treatments at low pH and viscosity. Not water activity but the kind of
      soluble solute used to lower water activity influenced inactivation. High NaCl
      concentrations lead to total inactivation, while sucrose and glycerol strongly
      protected the cells against inactivation.

PMID- 19157616
TI  - Development of a RAPD-PCR method for identification of Bacillus species isolated
      from Cheonggukjang.
AB  - A RAPD-PCR (Randomly Amplified Polymorphic DNA-PCR) method was developed for
      rapid identification of Bacillus species, especially B. subtilis, B.
      licheniformis, and B. amyloliquefaciens, the most frequently isolated organisms
      from fermented soy foods such as Cheonggukjang, a Korean traditional food. A RAPD
      PCR using a 10-mer (S-30) produced species specific bands reproducibly. All B.
      subtilis strains tested produced common bands of 0.5 and 0.88 kb in size. All B.
      amyloliquefaciens strains generated 1.1 and 1.5 kb bands together with 0.5 kb
      fragment whereas B. licheniformis strains produced 1.25, 1.70, and 1.9 kb bands
      with an occasional 0.5 kb band. Using the RAPD-PCR protocol, six bacilli strains
      isolated from Cheonggukjang were identified to the species level, which was
      difficult by 16S rRNA gene and recA gene sequencing for some isolates. The 0.5 kb
      fragment, the major band for B. subtilis strains, was an internal part of a ytcP
      gene encoding a hypothetical ABC-type transporter. A B. subtilis species specific
      primer pair was designed based on ytcP sequences and PCR using the primer pair
      produced a 0.46 kb fragment only from B. subtilis strains.

PMID- 19157617
TI  - A pilot randomised controlled trial of resistance exercise bands in the
      management of sedentary subjects with type 2 diabetes.
AB  - We conducted a 4-month randomised controlled trial of home-based resistance
      training using exercise bands, amongst people with type 2 diabetes and co
      morbidities limiting aerobic exercise capacity. The intervention did not improve
      HbA1c, anthropometric variables or functional capacity. We conclude that short
      term use of exercise bands does not improve glycaemic control.

PMID- 19157618
TI  - Glucose intolerance and diabetes as risk factors for cognitive impairment in
      people at high cardiovascular risk: results from the ONTARGET/TRANSCEND research
      programme.
AB  - AIMS: To assess the cross-sectional associations of the measures of glycemia and
      cognitive function in subjects at high cardiovascular risk. METHODS:  SETTING AND
      PATIENTS: The ONgoing Telmisartan Alone and in combination with Ramipril Global
      Endpoint Trial (ONTARGET) and concurrent Telmisartan Randomized Assessment Study
      in ACE intolerant Subjects with Cardiovascular Disease (TRANSCEND) are multi
      center, randomized, controlled investigations of different approaches to
      angiotensin receptor blockade in over 30,000 high CV risk subjects. Baseline data
      in both trials was used to analyze relationships between measures of glycemic
      control and cognition. OUTCOMES: The univariate and multivariate relationships
      between diabetes status, fasting plasma glucose (FPG), and scores on the Mini
      Mental State Examination (MMSE) were assessed. RESULTS: In subjects with
      diabetes, the mean MMSE score was 0.4 units lower than in those without diabetes
      (P<0.0001). In all subjects, a 1 mmol/L higher FPG value was associated with a
      MMSE score that was 0.06 units lower (P<0.0001). The association persisted after
      adjustment for several cardiovascular risk factors. CONCLUSIONS: Dysglycemia is a
      risk factor for impaired cognitive function in this broadly representative, high
      risk study population. Prospective studies can more reliably discern temporal
      associations, including the effects of glucose lowering in this clinical group.

PMID- 19157619
TI  - Hepatitis E virus as an emerging cause of chronic liver disease in organ
      transplant recipients.

PMID- 19157620
TI  - Alteration of protein glycosylation in liver diseases.
AB  - Chronic liver diseases are a serious health problem worldwide. The current gold
      standard to assess structural liver damage is through a liver biopsy which has
      several disadvantages. A non-invasive, simple and non-expensive test to diagnose
      liver pathology would be highly desirable. Protein glycosylation has drawn the
      attention of many researchers in the search for an objective feature to achieve
      this goal. Glycosylation is a posttranslational modification of many secreted
      proteins and it has been known for decades that structural changes in the glycan
      structures of serum proteins are an indication for liver damage. The aim of this
      paper is to give an overview of this altered protein glycosylation in different
      etiologies of liver fibrosis / cirrhosis and hepatocellular carcinoma. Although
      individual liver diseases have their own specific markers, the same modifications
      seem to continuously reappear in all liver diseases: hyperfucosylation, increased
      branching and a bisecting N-acetylglucosamine. Analysis at mRNA and protein level
      of the corresponding glycosyltransferases confirm their altered status in liver
      pathology. The last part of this review deals with some recently developed
      glycomic techniques that could potentially be used in the diagnosis of liver
      pathology.

PMID- 19157621
TI  - The impact of CYP2E1 on the development of alcoholic liver disease as studied in
      a transgenic mouse model.
AB  - BACKGROUND/AIMS: CYP2E1 metabolizes ethanol, generates reactive oxygen species,
      and is suggested to be important for development of alcoholic liver disease. The
      present study aims to evaluate the role of CYP2E1 in combination with ethanol for
      development of alcoholic liver disease using mice transgenic for the human CYP2E1
      gene. METHODS: Changes in hepatic gene expression were monitored in controls and
      mice transgenic for human CYP2E1, treated with ethanol or isocaloric dextrose
      intragastrically for 4 weeks, and related to pathology using Affymetrix
      microarrays and TaqMan RealTime PCR. RESULTS: Presence of the CYP2E1 transgene
      increased liver injury and increased expression of stress related genes.
      Microarray analyses revealed the expression of structural genes, particularly
      cytokeratin 8 and 18, to be highly related to pathology. CONCLUSIONS: This in
      vivo study confirms several findings regarding CYP2E1 and alcohol previously
      found only in vitro. These results provide in vivo evidence that CYP2E1
      overexpression aggravates hepatic injury, and suggest that expression of
      cytokeratins 8 and 18 can be considered as biomakers for the progression of
      alcoholic liver disease.

PMID- 19157623
TI  - Anti-HBs re-seroconversion after liver transplantation in a patient with past HBV
      infection receiving a HBsAg positive graft.
AB  - BACKGROUND/AIMS: Orthotopic liver transplantation (OLT) is an important
      therapeutic option for HBV-related end-stage-liver disease, yet it is often
      hampered by a scarcity of organ availability. One option to increase organ
      availability is the use of virologically compromised organs from HBV-infected
      donors. Transplantation of anti-HBcore positive grafts has been associated with a
      low risk of HBV recurrence if adequately treated with nucleoside analogs,
      irrespective of concomitant HBV-specific immunoglobulin therapy. Experience using
      HBsAg positive grafts is, however, very limited. METHODS: Here, the analysis of
      the cellular and humoral HBV-specific immunity of a subject with past HBV
      infection (anti-HBs and anti-HBc positive) receiving an HBsAg positive liver
      graft is reported. RESULTS: Nine months post-OLT, the patient experienced a
      spontaneous anti-HBs re-seroconversion allowing the discontinuation of HBIG. The
      data show a concurrent increase in the cellular and humoral immunity at times of
      reduced viral antigenemia, demonstrating effective immune control of HBV post
      OLT. CONCLUSIONS: These data support the use of marginal organs in this setting,
      providing a potential strategy to further alleviate organ shortage.

PMID- 19157624
TI  - When lightning strikes twice: the plot thickens for a dual role of the anion
      exchanger 2 (AE2/SLC4A2) in the pathogenesis and treatment of primary biliary
      cirrhosis.
AB  - BACKGROUND/AIMS: Cl(-)/HCO(3)(-) anion exchanger 2 (AE2) is involved in
      intracellular pH (pH(i)) regulation and transepithelial acid-base transport,
      including secretin-stimulated biliary bicarbonate excretion. AE2 gene expression
      was found to be reduced in liver biopsy specimens and blood mononuclear cells
      from patients with primary biliary cirrhosis (PBC), a disease characterized by
      chronic nonsuppurative cholangitis associated with antimitochondrial antibodies
      (AMA) and other autoimmune phenomena. In mice with widespread Ae2 gene
      disruption, we previously reported altered spermiogenesis and reduced gastric
      acid secretion. We now describe the hepatobiliary and immunologic changes
      observed in these Ae2(a,b)-deficient mice. METHODS: In this murine model,
      splenocyte pH(i) and T-cell populations were studied by flow cytometry. CD3
      stimulated cytokine secretion was estimated using cytokine arrays. AMA were
      evaluated by immunoblotting and proteomics. Hepatobiliary changes were assessed
      by immunohistopathology, flow cytometry, and serum biochemistry. Cholangiocyte
      gene expression was analyzed by real-time polymerase chain reaction. RESULTS:
      Ae2(a,b)(-/-) mice exhibit splenomegaly, elevated pH(i) in splenocytes, increased
      production of interleukin-12p70 and interferon gamma, expanded CD8(+) T-cell
      population, and under represented CD4(+)FoxP3(+)/regulatory T cells. Most
      Ae2(a,b)(-/-) mice tested positively for AMA, showing increased serum levels of
      immunoglobulin M and G, and liver-specific alkaline phosphatase. About one third
      of Ae2(a,b)(-/-) mice had extensive portal inflammation with CD8(+) and CD4(+) T
      lymphocytes surrounding damaged bile ducts. Cholangiocytes isolated from
      Ae2(a,b)(-/-) mice showed gene expression changes compatible with oxidative
      stress and increased antigen presentation. CONCLUSIONS: Ae2 deficiency alters
      pH(i) homeostasis in immunocytes and gene expression profile in cholangiocytes,
      leading to immunologic and hepatobiliary changes that resemble PBC.

PMID- 19157625
TI  - Angiogenesis in liver disease.
AB  - Angiogenesis and disruption of liver vascular architecture have been linked to
      progression to cirrhosis and liver cancer (HCC) in chronic liver diseases, which
      contributes both to increased hepatic vascular resistance and portal hypertension
      and to decreased hepatocyte perfusion. On the other hand, recent evidence shows
      that angiogenesis modulates the formation of portal-systemic collaterals and the
      increased splanchnic blood flow which are involved in the life threatening
      complications of cirrhosis. Finally, angiogenesis plays a key role in the growth
      of tumours, suggesting that interference with angiogenesis may prevent or delay
      the development of HCC. This review summarizes current knowledge on the molecular
      mechanisms of liver angiogenesis and on the consequences of angiogenesis in
      chronic liver disease. On the other hand, it presents the different strategies
      that have been used in experimental models to counteract excessive angiogenesis
      and its potential role in preventing transition to cirrhosis, development of
      portal hypertension and its consequences, and its application in the treatment of
      hepatocellular carcinoma.

PMID- 19157626
TI  - Hepatic microcirculation: a critical but neglected factor for the outcome of
      viral hepatitis.
AB  - More than 500 million people worldwide are persistently infected with hepatitis B
      virus or hepatitis C virus. Although both viruses are poorly cytopathic,
      persistence of either virus carries a risk of chronic liver inflammation,
      potentially resulting in liver steatosis, liver cirrhosis, end-stage liver
      failure or hepatocellular carcinoma. Virus-specific T cells are a major
      determinant of the outcome of hepatitis, as they contribute to the early control
      of chronic hepatitis viruses, but they also mediate immunopathology during
      persistent virus infection. We have analyzed the role of platelet-derived
      vasoactive serotonin during virus-induced CD8(+) T cell-dependent
      immunopathological hepatitis in mice infected with the noncytopathic lymphocytic
      choriomeningitis virus. After virus infection, platelets were recruited to the
      liver, and their activation correlated with severely reduced sinusoidal
      microcirculation, delayed virus elimination and increased immunopathological
      liver cell damage. Lack of platelet-derived serotonin in serotonin-deficient mice
      normalized hepatic microcirculatory dysfunction, accelerated virus clearance in
      the liver and reduced CD8(+) T cell-dependent liver cell damage. In keeping with
      these observations, serotonin treatment of infected mice delayed entry of
      activated CD8(+) T cells into the liver, delayed virus control and aggravated
      immunopathological hepatitis. Thus, vasoactive serotonin supports virus
      persistence in the liver and aggravates virus-induced immunopathology.

PMID- 19157627
TI  - Progression of HCV infection in patients with chronic kidney disease.

PMID- 19157628
TI  - Industry views of biosimilar development in Japan.
AB  - OBJECTIVE: To understand the issues around biosimilar development by
      pharmaceutical companies in Japan, which has emerged as an urgent issue in
      guaranteeing the availability of affordable biopharmaceuticals and a reduction in
      drug costs. METHODS: Various regulatory guidelines related to biosimilar
      development are carefully reviewed. We then interviewed representatives of 11
      Japanese companies to explore issues related to the manufacturing,
      immunogenicity, development costs and regulation of biosimilars. RESULTS: Our
      investigations show that Japan is unlikely to produce more than a handful of
      biosimilars domestically in the near future. We also found that regulatory
      guidelines for biosimilars will be needed for Japanese developers to plan and
      initiate production, in order to provide affordable biopharmaceuticals to
      Japanese patients. CONCLUSION: These results represent that regulatory guidelines
      for biosimilars, encouraging competition with maintaining incentive for
      innovation, will be needed for Japanese developers to plan and initiate
      biosimilar development.

PMID- 19157629
TI  - A perturbation-based estimate algorithm for parameters of coupled ordinary
      differential equations, applications from chemical reactions to metabolic
      dynamics.
AB  - Conversion of complex phenomena in medicine, pharmaceutical and systems biology
      fields to a system of ordinary differential equations (ODEs) and identification
      of parameters from experimental data and theoretical model equations can be
      treated as a computational engine to arrive at the best solution for chemical
      reactions, biochemical metabolic and intracellular pathways. Particularly, to
      gain insight into the pathophysiology of diabetes's metabolism in our current
      clinical studies, glucose kinetics and insulin secretion can be assessed by the
      ODE model. Parameter estimation is usually performed by minimizing a cost
      function which quantifies the difference between theoretical model predictions
      and experimental measurements. This paper explores how the numerical method and
      iteration program are developed to search ODE's parameters using the perturbation
      method, instead of the Gauss-Newton or Levenberg-Marquardt method. Several
      interesting applications, including Lotka-Volterra chemical reaction system,
      Lorenz chaos, dynamics of tetracycline hydrochloride concentration, and Bergman's
      Minimal Model for glucose kinetics are illustrated.

PMID- 19157630
TI  - IA-FEMesh: an open-source, interactive, multiblock approach to anatomic finite
      element model development.
AB  - Finite element (FE) analysis is a valuable tool in musculoskeletal research. The
      demands associated with mesh development, however, often prove daunting. In an
      effort to facilitate anatomic FE model development we have developed an open
      source software toolkit (IA-FEMesh). IA-FEMesh employs a multiblock meshing
      scheme aimed at hexahedral mesh generation. An emphasis has been placed on making
      the tools interactive, in an effort to create a user friendly environment. The
      goal is to provide an efficient and reliable method for model development,
      visualization, and mesh quality evaluation. While these tools have been
      developed, initially, in the context of skeletal structures they can be applied
      to countless applications.

PMID- 19157631
TI  - Measuring appropriate use of antibiotics in pyelonephritis in Belgian hospitals.
AB  - Inappropriate use of antibiotics can induce antibiotic resistance, treatment
      failure, increased costs and even mortality. We developed a methodology for
      measuring guideline compliance of hospital antibiotic prescriptions in community
      acquired acute pyelonephritis in Belgium. The claims and clinical data of all
      Belgian hospitalizations for community-acquired acute pyelonephritis were
      extracted from a nationwide administrative database. In a clinically homogeneous
      subset of patients, the percentage of patients who received a guideline-compliant
      prescription was calculated according to prescription guidelines disseminated in
      Belgium. In the group of non-pregnant adult female patients, 31% of the
      prescriptions were not in strict compliance with the guideline. Interhospital
      variability ranged from 0% to 100% compliance. We conclude that administrative
      databases can be used to analyze antibiotic prescription behavior in hospitals
      for homogeneous and clinically relevant patient groups. The interhospital
      variability observed in Belgian hospitals indicate that there is a clear room for
      improvement.

PMID- 19157632
TI  - Epidermal growth factor receptor tyrosine kinase inhibitors as a first-line
      therapy for never-smokers with adenocarcinoma of the lung having asymptomatic
      synchronous brain metastasis.
AB  - Considering whole-brain radiotherapy (WBRT) for asymptomatic brain metastases can
      reduce performance status and delay systemic treatment, primary chemotherapy can
      be a feasible alternative treatment. Good and rapid response to epidermal growth
      factor tyrosine kinase inhibitor (EGFR TKI) treatment makes this an attractive
      option for never-smokers with adenocarcinoma of the lung. Between January 2005
      and August 2007, 23 Korean never-smoking patients with adenocarcinoma of the lung
      who had synchronous asymptomatic brain metastasis were consecutively treated with
      EGFR TKI therapy, either gefitinib 250 mg or erlotinib 150 mg once daily, as
      first-line treatment after giving informed consent, until disease progression,
      unacceptable toxicity or patient's refusal. They have not received either any
      prior chemotherapy or any radiotherapy including stereotactic radiosurgery.
      Objective tumor responses were assessed 1 month after treatment and then every 2
      months or when clinically indicated. Out of the 23 patients treated, 16 achieved
      a PR and 3 experienced stable disease (SD) while 4 experienced progressive
      disease (PD), resulting in a response rate of 69.6% and a disease control rate of
      82.6%. Intracranial tumor responses were observed in 17 patients (73.9%). After a
      median follow-up of 21.8 months, the median progression-free and overall survival
      (OS) time was 7.1 and 18.8 months, respectively. Eleven patients received WBRT
      with a median time-to-local-treatment for intracranial tumors of 19.3 months. In
      conclusion, EGFR TKI treatment showed promising antitumor activity against both
      intracranial and extracranial tumors in chemotherapy-naive never-smokers with
      adenocarcinoma of the lung. Therefore, these agents should be considered as the
      treatment of choice in this clinical setting.

PMID- 19157633
TI  - Polymorphisms in XRCC1 and XPG and response to platinum-based chemotherapy in
      advanced non-small cell lung cancer patients.
AB  - Platinum-based chemotherapeutics is the most common regimens for advanced NSCLC
      patients. However, it is difficult to identify platinum resistance in clinical
      treatment. Genetic factors are thought to represent important determinants of
      drug efficacy. In this study, we investigated whether single nucleotide
      polymorphisms (SNPs) in Xeroderma pigmentosum group G (XPG) and X-ray repair
      cross complementing group 1 (XRCC1) were associated with the tumor response in
      non-small cell lung cancer (NSCLC) patients treated with platinum-based
      chemotherapy in Chinese population. Totally 82 patients with advanced NSCLC were
      routinely treated with cisplatin or carboplatin-based chemotherapy, and clinical
      response was evaluated after 2-3 cycles. And 3D (three dimensions) polyacrylamide
      gel-based DNA microarray method was used to evaluate the genotypes of XRCC1 194
      Arg/Trp, XRCC1 399Arg/Gln, XPG 46His/His and XPG 1104His/Asp in DNA from
      peripheral lymphocytes. We found that there was a significantly increased chance
      of treatment response to platinum-based chemotherapy with the XRCC1 194Arg/Trp
      genotype (odds ratio 0.429; 95% CI 0.137-1.671; P=0.035). The polymorphism of XPG
      46His/His was found to be associated with clinical response in NSCLC patients
      P=0.047, not detected between chemotherapy response and SNPs of XRCC1 399Arg/Gln
      or XPG 1104His/Asp (P=0.997 0.561, respectively). Our study showed that the
      polymorphic status of XRCC1 194Arg/Trp might be a predictive marker of treatment
      response for advanced NSCLC patients and those of XPG His46His was associated
      with susceptibility of chemotherapy. The 3D polyacrylamide gel-based DNA
      microarray method was accurate, high-throughput and inexpensive, especially
      suitable for a large scale of SNP genotyping in population.

PMID- 19157634
TI  - The role of celecoxib in Rad51 expression and cell survival affected by gefitinib
      in human non-small cell lung cancer cells.
AB  - Celecoxib (Celebrex) is a cyclooxygenase-2 (COX-2) selective inhibitor and
      gefitinib (Iressa(R), ZD1839) is a selective epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitor for human non-small cell lung cancer (NSCLC).
      The addition of celecoxib to gefitinib to prolong the survival of patients with
      NSCLC still remains controversial and needs to be investigated. The Rad51 protein
      is essential for homologous recombination repair, and is overexpressed in chemo-
      or radioresistant carcinomas. In this study, we characterize the role of
      celecoxib in the cytotoxicity, ERK1/2 activation and Rad51 expression affected by
      gefitinib in NSCLC cells. We show that celecoxib can enhance the cytotoxicity
      induced by gefitinib in NSCLC cells. Treatment with celecoxib alone has no effect
      on the ERK1/2 activation, Rad51 mRNA and protein levels, however, combined
      treatment with gefitinib results in a significant reduction of phospho-ERK1/2 and
      Rad51 protein levels, and triggers the degradation of Rad51 via a 26S proteasome
      dependent pathway. Expression of constitutively active MKK1/2 vectors (MKK1/2-CA)
      significantly rescues the decreased ERK1/2 activity, and restores Rad51 protein
      levels and cell survival under co-treatment with gefitinib and celecoxib.
      Furthermore, blocking ERK1/2 activation by U0126 (MKK1/2 inhibitor) and knocking
      down Rad51 expression by transfection with small interfering RNA of Rad51 can
      enhance the cytotoxicity of celecoxib.

PMID- 19157635
TI  - Accuracy and prognostic impact of a vessel invasion grading system for stage IA
      non-small cell lung cancer.
AB  - BACKGROUND: Despite the recognition that lymphatic and blood vessel invasion is
      an important prognostic factor in lung cancer, there is no common definition for
      pathological evaluation of vessel invasion. The aim of the present study was to
      determine whether D2-40 immunostaining can increase the accuracy of detection of
      lymphatic vessel invasion and whether our new grading system of vessel invasion
      by "degree" could be used instead of conventional evaluation by "presence" for
      pathological stage IA non-small cell lung cancer (NSCLC). METHODS: The vessel
      invasion classification was re-evaluated in 221 recent paraffin-embedded sections
      of p-stage IA NSCLC stained by Hematoxylin-Eosin (HE), Elastica-Van-Gieson (EVG),
      and D2-40. RESULTS: After re-assessment using D2-40 immunostaining, 41.2% (31 of
      75) of ly1 cases by HE/EVG changed to ly0, and 14.9% (17 of 114) of ly0 cases by
      HE/EVG changed to ly1. Overall, 4 of 28 ly2 cases on conventional staining were
      changed to ly1, and 2 were changed to ly0 using D2-40 immunostaining. When the
      patients were divided into two groups by the presence of vessel invasion (v/ly0
      vs. 1, 2, 3), there was no significant difference in cancer-specific survival
      (p=0.1107, 0.0875, respectively), while when they were divided according to
      degree of vessel invasion (v/ly0, 1 vs. 2, 3), there was a statistically
      significant difference (p=0.0038, p=0.0002, respectively). On multivariate
      analysis, lymphatic vessel invasion had a significant impact on cancer-specific
      survival (p=0.0061). CONCLUSION: Our results suggest that D2-40 immunostaining
      provides a precise diagnosis of lymphatic vessel invasion, and our new grading
      system of vessel invasion by "degree" is accurate and has prognostic value in
      early lung cancer.

PMID- 19157636
TI  - Angiogenetic biomarkers in non-small cell lung cancer with malignant pleural
      effusion: correlations with patient survival and pleural effusion control.
AB  - OBJECTIVE: To evaluate how the angiogenetic biomarkers vascular endothelial
      growth factor (VEGF), basic fibroblast growth factor (bFGF), and interleukin-8
      (IL-8) in the fluid of non-small cell lung cancer (NSCLC) with malignant pleural
      effusion (MPE) correlate with patient survival and pleural effusion control.
      DESIGN: Prospective study. PATIENTS AND METHODS: From April 1, 1998 to April 30,
      2005, we used thoracoscopic biopsy to collect pleural specimens and pleural
      effusion from 97 patients with NSCLC and MPE. Paired blood samples were
      harvested. We used enzyme-linked immunosorbent assays to evaluate levels of
      angiogenic factors in MPE and blood, and immunohistochemical staining to evaluate
      them in pleural specimens. Related data, such as patient survival and PE control,
      were collected for correlation analysis. RESULTS: Smoking and PE VEGF >1350 ng/mL
      were both significant negative predictors of patient survival. A trapped lung was
      the only significant factor for poor PE control. The serum level, the amount of
      PE, and the number of red blood cells in PE correlated well with PE VEGF level.
      Immunohistochemical staining of pleural samples showed that VEGF was secreted by
      both mesothelial and tumor cells. The level of PE IL-8 weakly correlated with PE
      VEGF, and the level of bFGF was not significant. CONCLUSIONS: PE VEGF was a
      useful angiogenetic factor for the amount of fluid in patients with NSCLC and
      MPE. In addition to smoking, PE VEGF >1350 ng/mL was a significant negative
      predictor of patient survival.

PMID- 19157637
TI  - Mode of cytotoxic action of T cell-engaging BiTE antibody MT110.
AB  - MT110 is an EpCAM/CD3-bispecific antibody construct in clinical development for
      the treatment of patients with adenocarcinoma expressing EpCAM (CD326). Like
      other members of this antibody class, MT110 can engage resting, polyclonal CD8(+)
      and CD4(+) T cells for highly potent redirected lysis of target cells. Here we
      further explored the mechanism of this action. Complete lysis of EpCAM(+) Kato
      III gastric cancer cells by previously unstimulated T cells was achieved within
      48 h. During this period, a high percentage of CD4(+) and CD8(+) T cells became
      activated and increased expression of granzyme B. This apparently boosted the
      capacity for serial target cell lysis as studied at very low effector-to-target
      ratios. Elimination of cancer cells by MT110-redirected T cells involved membrane
      damage as was evident from nuclear uptake of propidium iodide and release of the
      cytosolic enzyme adenylate kinase. Redirected T cells also potently triggered
      programmed cell death in cancer cells as was evident by membrane blebbing,
      activation of procaspases 3 and 7, fragmentation of nuclear DNA and cleavage of
      the caspase substrate poly (ADP ribose) polymerase. Chelation of extracellular
      calcium fully protected cancer cells from lysis by MT110-redirected T cells,
      while the pan-caspase inhibitor Z-VAD-FMK blocked activation of procaspases,
      cleavage of poly (ADP ribose) polymerase and fragmentation of nuclear DNA in
      cancer cells, but could not prevent nuclear uptake of propidium iodide. Soluble
      factors did not significantly contribute to cancer cell death. Our study shows
      that MT110 can efficiently gear up the potential of CD8(+) and CD4(+) T cells for
      serial lysis, and mediate kill of cancer cells predominantly through poreforming
      and pro-apoptotic components of cytotoxic T cell granules.

PMID- 19157638
TI  - Differential role of the Ca(2+) sensor synaptotagmin VII in macrophages and
      dendritic cells.
AB  - Synaptotagmin VII (Syt VII) is a Ca(2+) sensing molecule that regulates lysosomal
      exocytosis in several cell types. In macrophages (MO), Syt VII is required for
      efficient uptake of large particle loads, by promoting the delivery of lysosomal
      membrane to phagocytic cups. Here we compare the phagocytic capacity of bone
      marrow-derived MOs and dendritic cells (DC), and show that the requirement for
      Syt VII correlates with the unique ability of MOs for continuous phagocytosis. In
      contrast to MOs, Syt VII(+/+) and Syt VII(-/-) immature DCs show similar levels
      of initial phagocytosis, followed by a marked decrease in particle uptake.
      [Ca(2+)](i) chelation and PI-3 kinase inhibition reduce particle uptake by MOs,
      but are markedly less inhibitory in DCs. Thus, immature DCs appear to lack the
      Syt VII, Ca(2+) and PI-3 kinase-dependent forms of phagocytosis that are present
      in MOs. Interestingly, expression of Syt VII is up-regulated during LPS-induced
      DC maturation, a stimulus that also induces Syt VII translocation from
      intracellular compartments to the plasma membrane. Syt VII(-/-) DCs show a
      delayed translocation of MHC class II to the cell surface during maturation,
      consistent with the possibility that Syt VII facilitates exocytosis and/or
      surface retention of molecules critical for antigen presentation.

PMID- 19157639
TI  - Isolation and functional analysis of LiYAB1, a YABBY family gene, from lily
      (Lilium longiflorum).
AB  - YABBY family proteins are plant-specific transcriptional factors. YABBY genes can
      be divided into three subfamilies. Within the CRC/DL subfamily, the Arabidopsis
      CRC (CRABS CLAW) and the rice DL (DROOPING LEAF) have functionally diverged in
      the control of leaf development. CRC has no function in leaf development, while
      DL plays an important role in the formation of leaf midribs. In this study
      LiYAB1, an ortholog of CRC/DL genes from lily (Lilium longiflorum), was isolated
      by screening a cDNA library derived from young lily flower buds. Subcellular
      localization analysis indicated that LiYAB1 is nuclear localized. LiYAB1 is
      expressed strongly in the carpels of the lily flower and weakly in the leaves,
      which is similar to DL in rice. Ectopic expression of LiYAB1 in the rice dl
      mutant could rescue the drooping leaf phenotype of dl in some of the transgenic
      rice plants and cause abnormal leaves in the other transgenic plants. The
      overexpression of LiYAB1 in the wild-type Arabidopsis caused leaf abnormality.
      The results suggest that LiYAB1, a member of the CRC/DL subfamily genes, might
      have an important function in regulating the leaf development in lilies, as DL
      does in rice.

PMID- 19157640
TI  - Analysis of the soluble cell wall proteome of gymnosperms.
AB  - We analyzed the cell wall proteome of lignifying suspension cell cultures (SCCs)
      from four gymnosperms that differ in evolution degree. This analysis showed the
      presence of "peptide sequence tags" (PSTs) corresponding to glucan endo-1,3-beta
      D-glucosidase, xyloglucan-endotrans-glucosylase/hydrolase, chitinases, thaumatin
      like proteins and proteins involved in lignin/lignan biosynthesis, such as
      dirigent-like proteins and peroxidases. Surprisingly, and given the abundance of
      peroxidases in the cell wall proteome of these gymnosperms, PSTs corresponding to
      peroxidases were only detected in tryptic fragments of the cell wall proteome of
      Cycas revoluta. The current lack of knowledge regarding C. revoluta peroxidases
      led us to purify, characterize and partially sequence the peroxidases responsible
      for lignin biosynthesis in this species. This yielded three peroxidase-enriched
      fractions: CrPrx 1, CrPrx 2 and CrPrx 3. Analyses of tryptic peptides of CrPrx 2
      (32kDa) and CrPrx 3 (26kDa) suggest that CrPrx 3 arises from CrPrx 2 by protein
      truncation, and that CrPrx 3 apparently constitutes a post-translational
      modification of CrPrx 2. That CrPrx 2 and CrPrx 3 are apparently the same enzyme
      was also deduced from the similarity between the k(cat) shown by both peroxidases
      for the three monolignols. These results emphasize the analogies between the cell
      wall proteome of gymnosperms and angiosperms, the complexity of the peroxidase
      proteome, and the difficulties involved in establishing fine structure-function
      relationships.

PMID- 19157641
TI  - Narrowband ultraviolet B phototherapy and 308-nm excimer laser in the treatment
      of vitiligo: a review.
AB  - Vitiligo is a common and chronic disease with a great impact on patients' quality
      of life. Phototherapy with narrowband ultraviolet B radiation and excimer laser
      are two treatment modalities that are used increasingly for the management of the
      disease with variable results. In this article, we review the efficacy, adverse
      effects, and possible mechanisms of action of narrowband ultraviolet B and
      excimer laser in the management of vitiligo. Available data concerning the follow
      up of treated patients and some criteria for the selection of patients with a
      greater chance to respond satisfactorily to treatment are also presented.

PMID- 19157642
TI  - Use of complementary and alternative medicine among adults with skin disease:
      results from a national survey.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is commonly used for a
      variety of diseases in the United States. Limited population-based data exist on
      CAM use among patients with dermatologic conditions OBJECTIVE: We sought to
      determine the extent and the nature of CAM use in the United States among people
      with skin problems. METHODS: We conducted a cross-sectional survey using the 2002
      National Health Interview Survey and the Alternative Health Supplement. RESULTS:
      Among those reporting skin problems in the past year, 49.4% (95% confidence
      interval 47.2-51.6) had used CAM. Only 6.0% of this group (95% confidence
      interval 4.2-7.7) used CAM specifically for skin disease. Those reporting skin
      problems were more likely to use CAM than those who did not report skin problems
      (odds ratio 1.7, P < or = .001, 95% confidence interval 1.6-1.8). The most
      commonly used CAM modality was nonvitamin, nonmineral, natural products (ie,
      herbals). LIMITATIONS: Because of the nature of a cross-sectional study, it is
      not possible to know whether the skin problem or the CAM use came first (except
      in situations where they used CAM specifically for skin problems). Because this
      is not a dermatology-focused database, the definition of skin disease is vague.
      CONCLUSION: CAM use among adults with skin problems in the Unites States is
      common. Dermatologists should have candid discussions with their patients
      regarding CAM use.

PMID- 19157643
TI  - Outcome of late-onset hospital-acquired pneumonia related to causative organism.
AB  - Pneumonia caused by Pseudomonas spp. has been associated with an increase in
      mortality in critical care patients. Previous assessments, however, have failed
      to compare outcome solely with other pathogens associated with hospital-acquired
      pneumonia (HAP). We have performed a retrospective review of all critical care
      patients with late-onset HAP (hospital inpatient stay >72 h at time of diagnosis)
      due to pure respiratory cultures of Pseudomonas spp., meticillin-resistant
      Staphylococcus aureus (MRSA) or non-pseudomonal Gram-negative (NPGN) organisms
      from 1998 to 2007. Casenote review involved assessments of illness severity,
      clinical pulmonary infection scoring (CPIS), critical care and hospital survival,
      and critical care length of stay. Out of 252 casenotes, 204 were reviewed. There
      were 186 treated cases of pneumonia. Ten patients had both pseudomonal and NPGN
      pneumonias during the same admission and two patients presented with community
      acquired infections due to these organisms. These 12 patients were excluded from
      further analysis. Of the remaining 174 patients, 80 were infected with
      pseudomonas, 40 with MRSA and 54 had NPGN organisms. The three groups of patients
      were well-matched, with similar age, sex, CPIS scores, incidence of bacteraemia
      and Acute Physiology and Chronic Health Evaluation II scores at diagnosis. There
      were no outcome differences between the groups with respect to hospital and
      critical care survival and critical care length of stay. In this series, there
      appears to be no survival disadvantage associated with pseudomonal pneumonia when
      compared with other hospital-acquired organisms associated with HAP, where
      disease severity between the groups is similar.

PMID- 19157644
TI  - Predominance of the Hungarian clone (ST 239-III) among hospital-acquired
      meticillin-resistant Staphylococcus aureus isolates recovered throughout mainland
      China.
AB  - Multilocus sequence typing (MLST) data have revealed many insights into the
      global epidemiology of Staphylococcus aureus but, with notable exceptions such as
      Japan, the evidence from most Asian countries is currently limited. Here we have
      applied MLST to 132 hospital-acquired meticillin-resistant Staphylococcus aureus
      (HA-MRSA) isolates collected in mainland China in 2002. In all, 102 isolates were
      recovered from a single tertiary hospital in Guangzhou, South China, and the
      remaining 30 isolates were recovered from six metropolitan tertiary hospitals
      from geographically diverse districts corresponding to a total area of more than
      2 million km2. The data reveal a striking predominance throughout mainland China
      of a single clonal lineage, ST 239, which accounts for 97% of the 132 isolates.
      These data support more limited evidence from previous studies suggesting the
      widespread predominance of ST 239 throughout hospitals in China, a pattern which
      possibly extends to the whole of continental Asia. Staphylococcal chromosome
      cassette mec (SCCmec) typing confirmed the homogeneity of the ST 239 isolates,
      with the vast majority corresponding to the Hungarian clone (ST 239-III).

PMID- 19157645
TI  - Risk factors for extended-spectrum beta-lactamase-producing Klebsiella pneumoniae
      and Escherichia coli acquisition in a tertiary care teaching hospital in
      Thailand.

PMID- 19157647
TI  - 'Dog days' surgical site infections in a Finnish trauma hospital during 2002
      2005.

PMID- 19157648
TI  - Prolonged norovirus outbreak in a Finnish tertiary care hospital caused by GII.4
      2006b subvariants.
AB  - Norovirus outbreaks are difficult to control in hospitals. Cohorting and contact
      isolation, disinfective surface cleaning and hand hygiene are key elements in
      outbreak control. A new norovirus variant, GII.4.-2006b, spreading across many
      continents, caused an exceptionally long epidemic period in Finland, from
      November 2006 to June 2007. Here, we describe the clinical and molecular
      characteristics of a norovirus outbreak in a large tertiary care hospital in
      Finland. Altogether 240 (18%) patients and 205 (19%) healthcare workers fell ill
      in the 504 bedded main building of Helsinki University Central Hospital during
      December 2006 to May 2007. The epidemic curve had three peaks in January,
      February and April, and different wards were affected each time. During the
      outbreak, 502 patient stool specimens were tested for norovirus RNA, 181 (36%) of
      which were positive. Molecular analysis of 48 positive specimens revealed three
      main subvariants of GII.4.-2006b circulating temporally within distinct wards. Of
      all microbiologically confirmed cases, 121 (67%) were nosocomial and nine (5%)
      died within 30 days of diagnosis. Molecular analysis suggested that the three
      main GII.4-2006b subvariants entered the hospital with gastroenteritis patients,
      and the nosocomial spread within wards coincided with the epidemic peaks. Active
      control measures, including temporary closure of the wards, ultimately confined
      the single-ward outbreaks. A prolonged outbreak in the community was probably the
      source for the prolonged outbreak period in the hospital.

PMID- 19157649
TI  - Anyone, anything, anytime...All the time.

PMID- 19157650
TI  - Chest computed tomography in the emergency department for suspected pulmonary
      embolism: it's time to practice what we preach.

PMID- 19157651
TI  - Safety and injury profile of conducted electrical weapons used by law enforcement
      officers against criminal suspects.
AB  - STUDY OBJECTIVE: Conducted electrical weapons such as the Taser are commonly used
      by law enforcement agencies. The safety of these weapons has been the subject of
      scrutiny and controversy; previous controlled studies in animals and healthy
      humans may not accurately reflect the risks of conducted electrical weapons used
      in actual conditions. We seek to determine the safety and injury profile of
      conducted electrical weapons used against criminal suspects in a field setting.
      METHODS: This prospective, multicenter, observational trial tracked a consecutive
      case series of all conducted electrical weapon uses against criminal suspects at
      6 US law enforcement agencies. Mandatory review of each conducted electrical
      weapon use incorporated physician review of police and medical records. Injuries
      were classified as mild, moderate, or severe according to a priori definitions.
      The primary outcome was a composite of moderate and severe injuries, termed
      significant injuries. RESULTS: Conducted electrical weapons were used against
      1,201 subjects during 36 months. One thousand one hundred twenty-five subjects
      (94%) were men; the median age was 30 years (range 13 to 80 years). Mild or no
      injuries were observed after conducted electrical weapon use in 1,198 subjects
      (99.75%; 95% confidence interval 99.3% to 99.9%). Of mild injuries, 83% were
      superficial puncture wounds from conducted electrical weapon probes. Significant
      injuries occurred in 3 subjects (0.25%; 95% confidence interval 0.07% to 0.7%),
      including 2 intracranial injuries from falls and 1 case of rhabdomyolysis. Two
      subjects died in police custody; medical examiners did not find conducted
      electrical weapon use to be causal or contributory in either case. CONCLUSION: To
      our knowledge, these findings represent the first large, independent, multicenter
      study of conducted electrical weapon injury epidemiology and suggest that more
      than 99% of subjects do not experience significant injuries after conducted
      electrical weapon use.

PMID- 19157652
TI  - Validation of 3 termination of resuscitation criteria for good neurologic
      survival after out-of-hospital cardiac arrest.
AB  - STUDY OBJECTIVE: Several termination of resuscitation criteria have been proposed
      to identify patients who will not survive to hospital discharge after out-of
      hospital cardiac arrest. However, only 1 set has been derived to specifically
      predict survival to hospital discharge with good neurologic function. The
      objectives of this study were to externally validate the basic life support (BLS)
      termination of resuscitation, advanced life support (ALS) termination of
      resuscitation, and neurologic termination of resuscitation criteria and compare
      their abilities to predict survival to hospital discharge with good neurologic
      function after out-of-hospital cardiac arrest. METHODS: This was a secondary
      analysis of the Denver Cardiac Arrest Registry. Consecutive adult nontraumatic
      cardiac arrest patients in Denver County from January 1, 2003, through December
      31, 2004, were included in the study. The BLS termination of resuscitation, ALS
      termination of resuscitation, and neurologic termination of resuscitation
      criteria were applied to the cohort, and their predictive proportions and 95%
      confidence intervals (CIs) were calculated for each set of criteria. RESULTS: Of
      the 715 patients included in this study, the median age was 65 years
      (interquartile range 52 to 78 years), and 69% were male patients. In addition,
      223 (31%) had return of spontaneous circulation, 175 (24%) survived to hospital
      admission, 58 (8%) survived to hospital discharge, and 42 (6%) survived to
      hospital discharge with good neurologic function. The proportion of patients with
      good neurologic survival to hospital discharge correctly identified for continued
      resuscitation was 100% (95% CI 92% to 100%) for all 3 termination of
      resuscitation criteria. The proportion of patients with poor neurologic survival
      to hospital discharge or no survival to hospital discharge correctly identified
      as eligible for termination of resuscitation was 36% (95% CI 32% to 40%) with the
      BLS termination of resuscitation criteria, 25% (95% CI 22% to 29%) with the ALS
      termination of resuscitation criteria, and 6% (95% CI 4% to 8%) with the
      neurologic termination of resuscitation criteria. Use of the BLS termination of
      resuscitation criteria would have reduced transport of the largest number of
      patients. CONCLUSION: All 3 termination of resuscitation criteria had equally
      high abilities to identify patients requiring continued resuscitation. The BLS
      termination of resuscitation criteria, however, had the best combined ability to
      predict good neurologic survival and poor neurologic survival or death. These
      findings and the relative simplicity of the BLS termination of resuscitation
      criteria support their use.

PMID- 19157653
TI  - Emergency department triage of acute myocardial infarction patients and the
      effect on outcomes.
AB  - STUDY OBJECTIVE: More than half of all acute myocardial infarction patients still
      do not meet benchmark reperfusion times, and the triage assessment that all
      patients receive when they arrive at an emergency department (ED) is a hospital
      level process that has not been studied as a potential contributor to delays. Our
      objective was to examine the triage of acute myocardial infarction patients (ST
      elevation and non-ST elevation myocardial infarction) and determine whether it is
      associated with subsequent delays in acute myocardial infarction processes of
      care. METHODS: We conducted a retrospective cohort analysis of a population-based
      cohort of acute myocardial infarction patients admitted to 102 acute care
      hospitals in Ontario, Canada, from July 2000 to March 2001. Main outcome measures
      were the rate of low-acuity triage (defined as a Canadian Triage and Acuity Scale
      score of III, IV, or V) among acute myocardial infarction patients and its
      association with delays in time from ED arrival to initial ECG (door-to-ECG time)
      and to administration of fibrinolysis (door-to-needle time). RESULTS: Among 3,088
      acute myocardial infarction patients, the rate of low acuity triage was 50.3%.
      Median door-to-ECG and door-to-needle time was 12.0 and 40.0 minutes,
      respectively. In adjusted quantile regression analyses, low-acuity triage was
      independently associated with a 4.4-minute delay in median door-to-ECG time and a
      15.1-minute delay in median door-to-needle time. The adjusted odds of achieving
      benchmark door-to-ECG and door-to-needle times were 0.54 (95% confidence interval
      0.46 to 0.65) and 0.44 (95% confidence interval 0.30 to 0.65), respectively, for
      acute myocardial infarction patients assigned a low-acuity ED triage score.
      CONCLUSION: Half of acute myocardial infarction patients were given a low acuity
      triage score when they presented to an ED in Ontario, which was independently
      associated with substantial delays in ECG acquisition and to reperfusion therapy.
      The quality of ED triage may be an important factor limiting performance on key
      measures of quality of acute myocardial infarction care.

PMID- 19157654
TI  - Effectiveness of nonresuscitative first aid training in laypersons: a systematic
      review.
AB  - STUDY OBJECTIVE: This study reviewed evidence on the effects of nonresuscitative
      first aid training on competence and helping behavior in laypersons. METHODS: We
      identified randomized and nonrandomized controlled trials and interrupted time
      series on nonresuscitative first aid training for laypersons by using 12
      databases (including MEDLINE, EMBASE, and PsycINFO), hand searching, reference
      checking, and author communication. Two reviewers independently evaluated
      selected studies with the Cochrane Effective Practice and Organisation of Care
      Review Group quality criteria. One reviewer extracted data with a standard form
      and another checked them. In anticipation of substantial heterogeneity across
      studies, we elected a descriptive summary of the included studies. RESULTS: We
      included 4 studies, 3 of which were randomized trials. We excluded 11 studies on
      quality issues. Two studies revealed that participants trained in first aid
      demonstrated higher written test scores than controls (poisoning first aid:
      relative risk 2.11, 95% confidence interval [CI] 1.64 to 2.72; various first aid
      cases: mean difference 4.75, 95% CI 3.02 to 6.48). Two studies evaluated helping
      responses during unannounced simulations. First aid training improved the quality
      of help for a bleeding emergency (relative risk 25.94; 95% CI 3.60 to 186.93),
      not the rate of helping (relative risk 1.13; 95% CI 0.88 to 1.45). Training in
      first aid and helping behavior increased the helping rates in a chest pain
      emergency compared with training in first aid only (relative risk 2.80; 95% CI
      1.05 to 7.50) or controls (relative risk 3.81; 95% CI 0.98 to 14.89).
      Participants trained in first aid only did not help more than controls (relative
      risk 1.36; 95% CI 0.28 to 6.61). CONCLUSION: First aid programs that also train
      participants to overcome inhibitors of emergency helping behavior could lead to
      better help and higher helping rates.

PMID- 19157655
TI  - Association of plutonium with sediments from the Ob and Yenisey Rivers and
      Estuaries.
AB  - The present study applied sequential extraction techniques to investigate the
      binding and mobility of plutonium (Pu) in sediments from the rivers and estuaries
      of the Ob and Yenisey. As a study site, the Ob and Yenisey are particularly
      interesting as both rivers have weapons-grade Pu sources in their catchment
      areas, including the Russian Pu production and reprocessing plants at Mayak,
      Tomsk-7 and Krashnoyarsk, and the Semipalantinsk nuclear weapons testing site in
      Kazakhstan. Plutonium activity and (240)Pu/(239)Pu ratios were determined using
      accelerator mass spectrometry (AMS). Sequential extractions showed that between
      47 and 80% of the Pu in Yenisey River sediments and 35-53% of the Pu in soils
      around the Techa River are mobilized with weak oxidising agents, which can
      indicate that Pu is bound to organic material. In contrast, Pu in Ob and Yenisey
      Estuarine sediments was more strongly bound, with 60-100% being found in the
      HNO(3)-extractable fraction. This change in speciation could reflect either that
      Pu bound to organic material in the Techa and Yenisey River sediments becomes
      more fixed to the sediments with time, or that organic-bound Pu is mobilized and
      released to the water when the sediments encounter the more saline water of the
      Ob and Yenisey estuaries. In general, (240)Pu/(239)Pu ratios were relatively
      consistent between different extraction fractions, although, in whole sediments,
      an increase in ratio was observed with distance from the source. This reflects
      the increased influence of weapon fallout from catchment runoff within the river
      systems, as compared to the weapons-grade sources close to the production and
      reprocessing plants. Knowledge of Pu speciation in the Ob and Yenisey Rivers, and
      the processes controlling its behaviour in estuarine systems, can improve
      predictions of its transfer and subsequent environmental impact to Arctic Seas.

PMID- 19157656
TI  - Review of Russian language studies on radionuclide behaviour in agricultural
      animals: 3. Transfer to muscle.
AB  - Over 150 publications reporting studies conducted in the former USSR were
      reviewed to provide transfer coefficients (F(f)) to the muscle of domestic
      animals from experiments using chronic administration, often for long timescales
      in large scale experiments. Only a few of these studies were made available in
      the English language literature or taken into account in international reviews.
      The values derived have been compared with expected values reported by the IAEA's
      Handbook of parameter values for the prediction of radionuclide transfer in
      temperate environments (TRS 364) where possible. The information presented here
      has been used in the current updating of parameters recommended for environmental
      assessments by the IAEA. Many of the reported values are for Sr due to the Mayak
      accident and Cs due to the Chernobyl accident. Nevertheless, the reported data
      for a wide range of radionuclides, in particular for Ru, Sb, and Zn markedly
      improve the extent of available data.

PMID- 19157657
TI  - Use of uterine dilators to create a safe tunnel for a microvascular pedicle in
      the radiated neck.

PMID- 19157658
TI  - Re: The use of epidural analgesia in lower limb free flap harvest.

PMID- 19157659
TI  - The need of postoperative radiographs in maxillofacial fractures--a prospective
      multicentric study.
AB  - There is still debate about the appropriateness of taking postoperative
      radiographs in the management of maxillofacial fractures. We did a prospective,
      multicentre study with predefined inclusion and exclusion criteria involving
      seven centres with a minimum sample size of 50 patients from each (total n=431).
      A standard data sheet was given to operators to record clinical and radiological
      variables before and after operation. The information obtained was analysed to
      evaluate the need for routine postoperative radiographs in the management of
      maxillofacial fractures. Patients were followed up for one month postoperatively.
      The parasymphyseal (n=240) was the most commonly encountered fracture site. The
      orthopantograph was the most commonly used radiograph, being recorded in 421
      cases (98%) before, and all 305 cases in which it was recommended after, the
      operation. Assessment of the reduction after fixation was the most common reason
      (n=237, 78%)) for advising postoperative radiographs. Intraoperative reduction
      and immediate postoperative occlusion were better indicators (p=0.02 and 0.01) of
      reduction, fixation, and clinical outcome than immediate postoperative
      radiographs. The practice of advising postoperative radiographs routinely should
      be discouraged as it has no significant role in the management of maxillofacial
      fractures.

PMID- 19157660
TI  - The behavior and effects of nanoparticles in the environment.

PMID- 19157661
TI  - Effects of six selected antibiotics on plant growth and soil microbial and
      enzymatic activities.
AB  - The potential impact of six antibiotics (chlortetracycline, tetracycline and
      tylosin; sulfamethoxazole, sulfamethazine and trimethoprim) on plant growth and
      soil quality was studied by using seed germination test on filter paper and plant
      growth test in soil, soil respiration and phosphatase activity tests. The
      phytotoxic effects varied between the antibiotics and between plant species
      (sweet oat, rice and cucumber). Rice was most sensitive to sulfamethoxazole with
      the EC10 value of 0.1 mg/L. The antibiotics tested inhibited soil phosphatase
      activity during the 22 days' incubation. Significant effects on soil respiration
      were found for the two sulfonamides (sulfamethoxazole and sulfamethazine) and
      trimethoprim, whereas little effects were observed for the two tetracyclines and
      tylosin. The effective concentrations (EC10 values) for soil respiration in the
      first 2 days were 7 mg/kg for sulfamethoxazole, 13 mg/kg for sulfamethazine and
      20 mg/kg for trimethoprim. Antibiotic residues in manure and soils may affect
      soil microbial and enzyme activities.

PMID- 19157662
TI  - Biomonitoring airborne parent and alkylated three-ring PAHs in the Greater
      Cologne Conurbation II: regional distribution patterns.
AB  - The spatial distribution of an important air pollutant class, three-ring
      polycyclic aromatic hydrocarbons and their derivatives (PAH-3), has been
      monitored for the Greater Cologne Conurbation (GCC) using pine needle as passive
      samplers. The GCC comprises one of the most heavily populated, trafficked, and
      industrialized regions in Germany. Here, 71 locations covering 3600 km(2) were
      sampled and, for the first time, isopleths maps constructed to investigate the
      regional variability in PAH-3 concentration and composition. The highest PAH-3
      loads on needles (1000-1500 ng g(-1)) were detected downwind of three lignite
      fuelled power plants, followed by Cologne City (600-700 ng g(-1)) and smaller
      towns (400-600 ng g(-1)), whereas rural and forest regions yielded PAH-3 loads of
      60-300 ng g(-1). PAH-3 ratios facilitated source reconciliation, with high
      dibenzothiophene versus retene values indicating lignite combustion and high
      9/(9+1)-methylphenanthrene ratios depicting traffic emissions in inner cities.
      PAH-3 ratios depended on topography and outlined the heavily industrialized Rhine
      Valley, demonstrating atmospheric dispersal of PAH-3.

PMID- 19157663
TI  - Biomonitoring airborne parent and alkylated three-ring PAHs in the Greater
      Cologne Conurbation I: temporal accumulation patterns.
AB  - Polycyclic aromatic hydrocarbons (PAHs) comprise an important group of air
      pollutants, with three-ring components (PAH-3) often dominating. Spatiotemporal
      variation in atmospheric PAH-3 can be analyzed by biomonitoring but high vapour
      pressure and low octanol-air-partitioning of PAH-3 cause dynamic accumulation on
      plant surfaces. This study for the first time shows that PAH-3 exhibit systematic
      accumulation trends on pine needles of 3-48 months of exposure time at six sites
      in Germany. Correlation of needle exposure time with PAH-3 concentration was
      r(2)=0.83 for phenanthrene and methylphenanthrenes, r(2)=0.77 for
      cyclopenta[def]phenanthrene, r(2)=0.60 for dibenzothiophene, r(2)=0.57 for
      dimethylphenanthrenes and r(2)=0.32 for retene. Variations in PAH-3 for summer
      and winter collected needles emphasize vegetation-air-partitioning influence on
      cumulative PAH-3 loads. PAH-3 ratios calculated for needle cohorts indicate
      persistence of original PAH patterns thus demonstrating the source-diagnostic
      potential of pine needle biomonitoring, which is utilized in part II of this
      study where spatial distribution of PAH-3 is investigated and related to emission
      sources.

PMID- 19157664
TI  - Why do Italian people rate their health worse than French people do? An
      exploration of cross-country differentials of self-rated health.
AB  - The prevalence of bad self-rated health (SRH) varies considerably across
      countries. Here we present the results of a cross-national comparative study
      based on the data of National Health Surveys conducted in France and Italy.
      According to these data, 11% of the Italian and 6% of the French adult population
      aged between 45 and 74 rate their health as bad or very bad. This gap may result
      from differences in population structure regarding the individual characteristics
      (sociodemographic characteristics, diseases and disabilities, lifestyle, and
      others) that impact on SRH i.e., a structural effect. It may also be that the
      link between these characteristics and SRH is "country-specific" i.e., a
      contextual effect. We use logistic regression models to assess the contribution
      of both explanations. We find that the structural effect plays a prominent role
      in the higher prevalence of bad SRH in Italy compared to France.

PMID- 19157665
TI  - The worlds of homeless white and African American youth in San Francisco,
      California: a cultural epidemiological comparison.
AB  - Research to date has given little attention to differences in the experience of
      youth homelessness by ethnicity. This article provides a comparative descriptive
      analysis of the effect of differences and similarities in paths to homelessness,
      self-perception, and survival strategies on health behaviors and consequent
      health outcomes of African American and white homeless youth in San Francisco,
      USA. We conducted participant observation and ethnographic interviews with 54
      youth primarily recruited from street venues. Hypotheses generated from the
      ethnographic data were validated in between-group analyses using concurrent
      epidemiological data collected from a sample of 205 youth. Our samples of
      unstably housed African American and white youth, though sharing common histories
      of family dysfunction, differed in both the ethnographic accounts and
      epidemiological analyses in their experiences of family, access to housing,
      street survival strategies, self-presentation, health behaviors and service
      utilization. Our sample of white youth generally identified with the term
      "homeless," engaged in survival activities associated with such a label, and
      accessed the services intended to address the needs of homeless youth. In
      contrast, our sample of African American youth generally did not perceive
      themselves as "homeless," a stigmatized term, and were thus less likely to
      utilize, or be accessed by, relevant services.

PMID- 19157666
TI  - Transitions in living arrangements of Canadian seniors: findings from the NPHS
      longitudinal data.
AB  - This paper examines transitions in living arrangement decisions of the seniors
      using the first six cycles of the Canadian longitudinal National Population
      Health Survey microdata. Transitions from independent to intergenerational and
      institutional living arrangements are uniquely analyzed using a discrete-time
      hazard rate multinomial logit modelling framework and accounted for unobserved
      individual heterogeneity in the data. Our results show: a) provision of publicly
      provided homecare reduces the likelihood of institutionalization, but it has no
      effect on intergenerational living arrangements; b) access to social support
      services reduces the probability of both institutional and intergenerational
      living arrangements; c) higher levels of functional health status, measured by
      Health Utility Index, reduce the probability of transitions from independent to
      intergenerational and institutional living arrangements; d) a decline in self
      reported health status increases the probability of institutionalization, but its
      effect on intergenerational living arrangements is statistically insignificant;
      e) higher levels of household income tend to decrease the probability of
      institutionalization; and f) the likelihood of transitioning to both
      intergenerational and institutional living arrangements increases with the
      duration of survival. Our findings suggest that access to and availability of
      publicly-provided homecare, social support services and other programs designed
      to foster better functional health status would contribute positively towards
      independent or intergenerational living arrangements and reduce the probability
      of institutionalization.

PMID- 19157667
TI  - Searching for and making meaning after breast cancer: prevalence, patterns, and
      negative affect.
AB  - This study describes the prevalence and patterns of searching for meaning in the
      aftermath of breast cancer and asks how the search relates to made meaning and
      emotional adjustment. Women (n=72) reported their level of searching for meaning,
      made meaning and negative affect at multiple time points in the first 18 months
      after breast cancer treatment. Over time, four search for meaning patterns
      emerged: continuous (44%), exiguous (28%), delayed (15%) and resolved (13%). Just
      over half of the participants reported having made meaning at early and late time
      points. A higher level of searching for meaning was unrelated to made meaning,
      but was associated with a higher level of negative affect in longitudinal
      analyses controlling for baseline levels. Women who engaged in an ongoing,
      unresolved search for meaning from baseline to follow-up also had a significantly
      higher level of negative affect at follow-up than women who infrequently or never
      engaged in a search for meaning over time. These analyses reveal that: a) there
      is great variability in the prevalence and pattern of searching for meaning in
      the aftermath of breast cancer, and b) searching for meaning may be both futile
      and distressing.

PMID- 19157668
TI  - Migration adversely affects antiretroviral adherence in a population-based cohort
      of HIV/AIDS patients.
AB  - Migration among persons with HIV/AIDS is common; however, it is not clear how
      migration relates to antiretroviral adherence, a key determinant of treatment
      efficacy. Therefore, our objective was to determine the scale of regional
      migration and its association with adherence patterns over time among HIV
      infected individuals in British Columbia (BC), Canada. Participants initiated
      HAART in August 1996-November 2004, and were followed until November 2005.
      Adherence was defined as the number of days worth of antiretrovirals dispensed
      divided by the number of days of follow-up (expressed as a percentage), and
      considered a binary time-dependent outcome: 'non-adherence' (less than 95%)
      versus 'adherence' (95% or more). Migration was calculated as the cumulative
      number of times a patient's residential address changed during the course of
      treatment, and treated as a time-dependent variable. Non-linear mixed-effects
      models were used to estimate the association between migration and adherence over
      time. All analyses were adjusted for relevant fixed and time-dependent variables.
      A total of 2421 participants were followed during the study period. Descriptive
      analysis demonstrated high stability in adherence over time, with more than 55%
      of patients moving at least once during the course of their treatment. We
      observed that those individuals migrating at least 3 times were 1.79 times more
      likely to be in the 'non-adherence' group than individuals who did not migrate.
      Our results demonstrate that migration in BC is not homogeneous across
      subpopulations. These results suggest that proactive strategies are needed to
      ensure that antiretroviral therapy remains available on a continued basis to
      highly migrant populations.

PMID- 19157669
TI  - Animal-human connections, "one health," and the syndemic approach to prevention.
AB  - A syndemic involves two or more afflictions that, by interacting synergistically,
      contribute to excess burdens of disease. A syndemic approach to prevention,
      meanwhile, focuses on connections among health-related problems, considers those
      connections when developing health policies, and aligns with forces for social
      change. In this short report, we expand the syndemic concept to acknowledge the
      extent to which animal health connects with human health and, with reference to
      existing publications, we demonstrate the pertinence of this expanded definition
      for a syndemic approach to prevention. Our demonstration assumes practical
      importance in relation to the concept of 'one health', which many prominent
      veterinary and human health scientists have recently endorsed as a sound basis
      for redressing human diseases, animal diseases, and environmental degradation
      worldwide. While social scientists have mostly ignored animal health, few 'one
      health' proponents have emphasized social conditions or involved social
      scientists. By explicitly accommodating animal-human connections in our expanded
      conceptualization of a syndemic, we hope to help create a space in which human
      health, veterinary, and social scientists may learn from one another, collaborate
      in research, and cooperate to clear the way for innovations in prevention.

PMID- 19157670
TI  - Video messaging: what works to persuade mothers to supervise young children more
      closely in order to reduce injury risk?
AB  - Recent research reveals that supervision can be a protective factor for childhood
      injury. Parents who closely supervise young children at home have children who
      experience fewer injuries. What is not known, however, is what messaging
      approaches (e.g., injury statistics, graphic images of injured children, personal
      testimonials by parents) are best to persuade parents to supervise more closely.
      Using video as the medium, the present focus group study of urban Canadian
      mothers explored their reactions to different formats and messages in order to:
      identify best practices to convince mothers that childhood injury prevention is
      important; determine how best to communicate messages about supervision to
      mothers; and identify what the nature and scope of these messages should be for
      motivating and empowering mothers to supervise closely. Results suggest that
      those who become aware of the scope of childhood injuries are motivated to pay
      attention to messaging about supervision, that such messages must be delivered
      with care so that parents do not feel guilty or blamed for acknowledging they
      could more closely supervise than they already are, that certain messages are not
      useful for encouraging closer supervision, and that both the content and
      presentation characteristics (images, accompanying sound) of messages are
      important determinants of effectiveness for motivating mothers to supervise more
      closely. Implications for developing interventions that effectively communicate
      information about child-injury risk and supervision to mothers are discussed.

PMID- 19157671
TI  - The effect of casein phosphopeptide-amorphous calcium phosphate on erosive enamel
      and dentine wear by toothbrush abrasion.
AB  - OBJECTIVE: In addition to its role as a remineralizing agent in preventing dental
      caries, calcium product (CPP-ACP) delivered as a mousse (Tooth Mousse, TM) can
      reduce erosion of enamel and dentine. The aim of this study was to determine
      whether CPP-ACP could also reduce erosive tooth wear involving toothbrush
      abrasion. METHODS: Flat, polished enamel and dentine specimens (n=72) were
      subjected to 10 wear regimes, with each regime involving erosion in 0.3% citric
      acid (pH 3.2) for 10 min followed by toothbrush abrasion in a slurry of fluoride
      free toothpaste and artificial saliva (1:3 ratio by weight) under a load of 2N
      for 200 cycles. The specimens were immersed in artificial saliva for 2h between
      wear regimes. In the experimental group 1, TM (containing CPP-ACP) was applied at
      the beginning of each wear episode for 5 min whereas TM- (without CPP-ACP) was
      applied in the experimental group 2. No mousse was applied in the control group.
      RESULTS: TM significantly reduced enamel wear (mean+/-S.E., 1.26+/-0.33 microm in
      the experimental group 1 vs 3.48+/-0.43 microm in the control group) and dentine
      wear (2.16+/-0.89 microm in the experimental group 1 vs 10.29+/-1.64 microm in
      the control group), and dentine wear was significantly less in the experimental
      group 1 than in the experimental group 2 (5.75+/-0.98 microm). CONCLUSION: The
      finding that TM reduced erosive tooth wear involving toothbrush abrasion,
      probably by remineralizing and lubricating eroded tooth surfaces, may have
      implications in the management of tooth wear.

PMID- 19157672
TI  - Effect of a 10% carbamide peroxide on wear resistance of enamel and dentine: in
      situ study.
AB  - OBJECTIVES: This triple-blind, 2x2 crossover in situ study, was undertaken to
      verify whether the wear resistance of enamel and root dentine would be affected
      by bleaching with a 10% carbamide peroxide agent and a placebo agent. METHODS:
      Thirty slabs of each substrate (2mm x 3mm x 2mm) were selected for each phase,
      after flattening and polishing procedures and microhardness test. After a 7-day
      lead-in period, one specimen of each substrate was randomly bonded on the facial
      surface of each one of 30 subject's upper second premolars. The volunteers
      received instructions on how to perform toothbrushing and application of gel in
      the tray. Fifteen volunteers bleached their maxillary arch with a 10% carbamide
      peroxide bleaching agent for a 2-week period, while the remainders used a placebo
      agent. After a 1-week washout period, a new set of enamel and root dentine slabs
      were bonded to the premolars and volunteers were crossed over to the alternate
      agent for 14 days. The resistance of enamel and root dentine to wear following
      bleaching, toothbrushing and intraoral exposure was measured with a profilometer,
      using reference areas. RESULTS: For enamel, ANOVA did not demonstrate significant
      difference between wear provided by placebo and bleaching agent (p=0.3713), but
      higher wear depth was observed for bleached root dentine (p=0.0346). CONCLUSIONS:
      While overnight bleaching caused no alteration in wear resistance of enamel, root
      dentine showed increased tissue loss.

PMID- 19157673
TI  - Researching the impact of oral health on diet and nutritional status:
      methodological issues.
AB  - OBJECTIVES: Assessment of the impact of dental function on diet and nutritional
      status requires robust methodologies and a standardised approach to increase
      accuracy of results and to facilitate cross study comparisons. The objectives of
      this paper are: to report the outcomes of a consensus workshop that critically
      reviewed publications reporting on dietary methodologies in relation to the
      impact of oral health on nutrition; to highlight future directions for research
      and; to make recommendations for appropriate use of methodologies for future
      research. DATA: Data relevant to nutrition and dental status published from 1980
      to 2005 in English were presented at the consensus workshop for discussion and
      appraisal. SOURCES: Relevant papers were retrieved through PubMed. Relevant texts
      were obtained from the library at Newcastle University, UK. STUDY SELECTION: A
      purposive sample of original articles that illustrated the application of a range
      of nutritional methodologies to the study of oral health impacts was identified.
      Original flagship texts on nutritional methodologies were reviewed. CONCLUSIONS:
      Numerous studies have shown an association between loss of teeth and inferior
      diet. Further research is required to elucidate the impact of novel approaches to
      prosthetic rehabilitation and the impact of contemporaneous dietary and dental
      intervention on diet, nutritional status, disease progression and quality of
      life. The recommendation of the consensus workshop was that future studies should
      adopt a comprehensive approach to the assessment of nutrition that encompasses
      measurement of diet, body composition, biochemical indices of intake and levels
      of nutrients, and functional biomarkers of disease.

PMID- 19157674
TI  - Emergency room management of trauma patients in Greece: preliminary report of a
      national study.
AB  - AIM OF THE STUDY: The aim of this study was to record and to evaluate the
      epidemiology of trauma in Greece and to assess the quality of management provided
      for trauma patients in the emergency department in Greek hospitals. METHODS: The
      Hellenic Society of Trauma and Emergency Surgery invited all the official
      representatives of the society throughout the country to participate in the
      study. The representatives that responded positively, met with the Board of the
      society in succeeding meetings to establish the reporting form and the inclusion
      criteria. Inclusion criteria were defined as trauma patients requiring admission,
      transfer to a higher level center or arrived dead or died in the emergency
      department of the reporting hospital. All reports were accumulated by the
      Hellenic Trauma society, imported in an electronic data base and analyzed. The
      design of the study was prospective and observational. RESULTS: In total 8862
      patients were included in the study in 12 months time. Of them 68.7% (n=6084)
      were male, aged 41.8+/-20.6 (mean+/-S.D.) and 31.3% were female (n=2778), aged
      52.7+/-24.1 (mean+/-S.D.). The mean duration of treatment in the emergency room
      department was 1h and 28min. Of the total number of patients, 2312 (26.1%) were
      initially assessed and managed by a specialist and 6249 (70.5%) were initially
      assessed and managed by a resident. CONCLUSIONS: Data from this study show that
      there is substantial room for improvement in the patient care in the emergency
      department following trauma. Further evaluation will be required to identify
      particular management patterns that can be readily altered.

PMID- 19157675
TI  - Performing bystander CPR for sudden cardiac arrest: behavioral intentions among
      the general adult population in Arizona.
AB  - STUDY OBJECTIVES: The odds of surviving an out-of-hospital cardiac arrest are
      significantly improved by the provision of bystander cardiopulmonary
      resuscitation (CPR), but many cardiac arrest victims do not receive it. The
      existing literature remains equivocal as to why people are unwilling to perform
      traditional CPR. This study's objectives were to determine the behavioral
      intentions of the general population in Arizona regarding performing bystander
      CPR and to assess the reasons for being unwilling to perform CPR. METHODS: This
      was a general population survey using a mailed, self-administered questionnaire.
      The questionnaire was mailed to random samples of Arizona residents in a rural
      and urban county. RESULTS: Usable questionnaires were received from 49.5% (n=370)
      and 49.6% (n=385) of the samples from the urban and rural county, respectively.
      More than 50% of respondents reported being willing to perform CPR on a stranger
      and over 80% reported being willing to perform CPR on a family member. There were
      no significant differences between the proportions of respondents in each county
      willing to perform CPR. The reasons for not being willing to perform CPR were
      relatively evenly divided among the five reasons listed. CONCLUSIONS: Although
      our findings likely overestimate the proportion of individuals who would perform
      bystander CPR, the relative importance of the reasons for not performing CPR is
      informative. Based on the reasons reported, there is potential to change the CPR
      related attitudes, beliefs, and skill levels of the general public to enhance the
      number of people willing and able to perform bystander CPR.

PMID- 19157676
TI  - Ectopic, autologous eutopic and normal endometrial stromal cells have altered
      expression and chemotactic activity of RANTES.
AB  - OBJECTIVE: To evaluate if the expression and chemotactic activity of RANTES are
      different in IL-1beta treated autologous eutopic endometrial stromal cells
      compared to ectopic and normal endometrium. STUDY DESIGN: Conditioned media from
      IL-1beta-treated ectopic, autologous eutopic and normal endometrial stromal cells
      were analyzed with a specific sandwich ELISA to quantify RANTES. The monocyte
      chemotactic activity of RANTES was assayed in a Boyden Chamber. RESULTS: RANTES
      expression in IL-1beta-treated autologous eutopic and normal endometrial stromal
      cells was significantly lower than ectopic endometrium. Autologous eutopic
      endometrial stromal cells showed a significant increase in RANTES expression
      compared to normal endometrium after IL-1beta stimulation for 60 h. The monocyte
      chemotactic activities of these conditioned media were highly correlated with the
      immunoreactive RANTES concentration. We observed significantly increased monocyte
      chemotactic activity in conditioned media of ectopic stromal cells compared to
      autologous eutopic and normal endometrium. The different chemotactic activity of
      RANTES between the autologous eutopic and normal endometrial stromal cells was
      also statistically significant. RANTES accounts for the majority (62%) of the
      monocyte chemotactic activity in ectopic endometrial stromal cells conditioned
      media and 55% of that activity in autologous eutopic endometrium. CONCLUSIONS:
      Although the eutopic endometric of women with and without endometriosis are
      histologically similar, our findings confirm that different expression and
      chemotactic activity of RANTES exist between autologous eutopic and normal
      endometrium. The altered expression of RANTES and monocyte chemotactic activity
      observed in ectopic, autologous eutopic and normal endometrium suggest the
      autologous eutopic endometrium may contribute to the pathogenesis of
      endometriosis.

PMID- 19157677
TI  - Ultrasound guided treatment of cornual ectopic pregnancy.

PMID- 19157678
TI  - Prolonged TPN during pregnancy in a cystic fibrosis patient with chronic
      pancreatitis.

PMID- 19157682
TI  - Structural effects in vitro of the anti-inflammatory drug diclofenac on human
      erythrocytes and molecular models of cell membranes.
AB  - Diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), has been widely
      investigated in terms of its pharmacological action, but less is known about its
      effects on cell membranes and particularly on those of human erythrocytes. In the
      present work, the structural effects on the human erythrocyte membrane and
      molecular models have been investigated and reported. This report presents the
      following evidence that diclofenac interacts with red cell membranes: a) X-ray
      diffraction and fluorescence spectroscopy of phospholipid bilayers showed that
      diclofenac interacted with a class of lipids found in the outer moiety of the
      erythrocyte membrane; b) in isolated unsealed human erythrocyte membranes (IUM)
      the drug induced a disordering effect on the acyl chains of the membrane lipid
      bilayer; c) in scanning electron microscopy (SEM) studies on human erythrocytes
      it was observed that the drug induced changes different from the normal biconcave
      morphology of most red blood cells. This is the first time in which structural
      effects of diclofenac on the human erythrocyte membrane have been described.

PMID- 19157683
TI  - Insights into the biology of mobilized hematopoietic stem/progenitor cells
      through innovative treatment schedules of the CXCR4 antagonist AMD3100.
AB  - OBJECTIVE: The CXCR4 antagonist AMD3100 mobilizes hematopoietic stem/progenitor
      cells (HSPC) in several species. Few data are available on the biology of HSPC
      mobilized with AMD3100 as single agent. To further study the kinetics and
      properties of AMD3100-mobilized HSPC, and to explore the size of mobilizable
      pools of HSPC targeted by AMD3100, we studied the effect of a continuous infusion
      scheme with saturating doses of AMD3100 [AMDi]. MATERIALS AND METHODS: Using
      established procedures, we evaluated mice mobilized with AMD3100, or those
      transplanted with AMD3100-mobilized HSPC. RESULTS: Relative to single-bolus
      AMD3100 [AMDb], the number of circulating CFU-C or CRU was dramatically higher
      after [AMDi]. During [AMDi], circulating CFU-C accumulated slowly, but after its
      discontinuation, CFU-C disappeared rapidly. Compared to bone marrow (BM)-c-kit(+)
      cells, AMD3100-mobilized (AMDb or AMDi) c-kit(+) cells showed reduced expression
      of several cytoadhesion molecules, similar to granulocyte colony-stimulating
      factor-mobilized c-kit(+) cells. In contrast to the latter, expression of CXCR4
      and CD26 were not reduced on AMD3100-mobilized c-kit(+) cells. BM homing of
      [AMDi]-mobilized CFU-C was >50% increased over normal BM-CFU-C. Hematopoietic
      recovery after transplantation of [AMDi]-mobilized peripheral blood was
      comparable to that of continuous infusion granulocyte colony-stimulating factor
      mobilized peripheral blood. AMD3100-mobilized HSPC were predominantly in G(0),
      and partial bromodeoxyuridine-labeling experiments documented underrepresentation
      of labeled cells (<5%) among [AMDb]-mobilized c-kit(+) cells, suggesting that
      cycling cells in BM, or those that recently completed cell cycle, are not
      targeted for mobilization by AMD3100. CONCLUSIONS: Our data demonstrate that
      [AMDi] is an efficacious mobilization scheme fully supporting transplantation
      demands and expands previous knowledge about properties and size of AMD3100
      sensitive BM-HSPC pools.

PMID- 19157684
TI  - Hoxa6 potentiates short-term hemopoietic cell proliferation and extended self
      renewal.
AB  - Hemopoietic progenitor cells express clustered homeobox (Hox) genes in a pattern
      characteristic of their lineage and stage of differentiation. In general, HOX
      expression tends to be higher in more primitive and lower in lineage-committed
      cells. These trends have led to the hypothesis that self-renewal of hemopoietic
      stem/progenitor cells is HOX-dependent and that dysregulated HOX expression
      underlies maintenance of the leukemia-initiating cell. Gene expression profile
      studies support this hypothesis and specifically highlight the importance of the
      HOXA cluster in hemopoiesis and leukemogenesis. Within this cluster HOXA6 and
      HOXA9 are highly expressed in patients with acute myeloid leukemia and form part
      of the "Hox code" identified in murine models of this disease. We have examined
      endogenous expression of Hoxa6 and Hoxa9 in purified primary progenitors as well
      as four growth factor-dependent cell lines FDCP-Mix, EML, 32Dcl3, and Ba/F3,
      representative of early multipotential and later committed precursor cells
      respectively. Hoxa6 was consistently higher expressed than Hoxa9, preferentially
      expressed in primitive cells and was both growth-factor and cell-cycle regulated.
      Enforced overexpression of HOXA6 or HOXA9 in FDCP-Mix resulted in increased
      proliferation and colony formation but had negligible effect on differentiation.
      In both FDCP-Mix and the more committed Ba/F3 precursor cells overexpression of
      HOXA6 potentiated factor-independent proliferation. These findings demonstrate
      that Hoxa6 is directly involved in fundamental processes of hemopoietic
      progenitor cell development.

PMID- 19157685
TI  - Proteasome proteolytic profile is linked to Bcr-Abl expression.
AB  - OBJECTIVE: We have previously demonstrated that proteasome activity is higher in
      bone marrow from patients with chronic myeloid leukemia (CML) than normal
      controls. This study investigates whether there is any relationship between Bcr
      Abl expression and proteasome activity. MATERIALS AND METHODS: Fluorogenic
      substrate assays and an activity-based probe were used to profile proteasome
      activity in CML cell-line models and the effect of the proteasome inhibitor
      BzLLLCOCHO on these cell-line models and primary CML cells was investigated.
      RESULTS: We have demonstrated that oncogenic transformation by BCR-ABL is
      associated with an increase in proteasome proteolytic activity. Furthermore,
      small interfering RNA targeted against BCR-ABL reduces proteasome activity. In
      addition, we have found that Bcr-Abl-positive cells are more sensitive than Bcr
      Abl-negative cells to induction of apoptosis by the proteasome inhibitor
      BzLLLCOCHO, and that sequential addition of imatinib followed by BzLLLCOCHO has
      an additive effect on the induction of apoptosis in Bcr-Abl-positive cells.
      Finally, we demonstrate that cell lines that become resistant to imatinib remain
      sensitive to proteasome inhibition. CONCLUSION: This is the first time that a
      direct relationship has been demonstrated between BCR-ABL transformation and the
      enzymatic activity of the proteasome. Our results suggest that the proteasome
      might provide a useful therapeutic target in CML, particularly in those patients
      who have developed resistance to conventional treatment.

PMID- 19157686
TI  - Structure and thermal stability of toxic chromium(VI) species doped onto TiO(2)
      powders through heat treatment.
AB  - Chromium(VI)-containing sorbents in the form of sludge or solid residue from
      treatment processes are often landfilled or used as fill materials, therefore the
      long-term stability of metal binding is important. The reduction of Cr(VI)
      Cr(III) through heat treatment may be a useful detoxification method. After
      heating at 500, 900, 1000, and 1100 degrees C for 4h, the transformation of
      chemical states of chromium on 105 degrees C-dried, 7.9% Cr(VI)-doped TiO(2)
      powders was studied on the basis of surface area measurements, scanning electron
      microscopy (SEM) images, X-ray diffraction (XRD), and extended X-ray absorption
      fine structure (EXAFS) spectra. It was shown that Cr(VI) was reduced to Cr(III)
      in the Cr(VI)-doped samples after heating within 500-900 degrees C. The present
      results also suggested that the chromium octahedral was bridged to the titanium
      tetrahedral and was incorporated in TiO(2) minerals formed after 1000 degrees C
      treatment.

PMID- 19157687
TI  - The updated EAU guidelines on muscle-invasive and metastatic bladder cancer.
AB  - CONTEXT: New data regarding diagnosis and treatment of muscle-invasive and
      metastatic bladder cancer (MiM-BC) has emerged and led to an update of the
      European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review
      the new EAU guidelines for MiM-BC. EVIDENCE ACQUISITION: A comprehensive workup
      of the literature obtained from Medline, the Cochrane central register of
      systematic reviews, and reference lists in publications and review articles was
      developed and screened by a group of urologists, oncologists, and radiologist
      appointed by the EAU Guideline Committee. Previous recommendations based on the
      older literature on this subject were taken into account. Levels of evidence and
      grade of guideline recommendations were added, modified from the Oxford Centre
      for Evidence-based Medicine Levels of Evidence. EVIDENCE SYNTHESIS: The diagnosis
      of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR)
      and following histopathologic evaluation. Patients with confirmed muscle-invasive
      BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and
      pelvis, if available. Adjuvant chemotherapy is currently only advised within
      clinical trials. Radical cystectomy (RC) is the treatment of choice for both
      sexes, and lymph node dissection should be an integral part of cystectomy. An
      orthotopic bladder substitute should be offered to both male and female patients
      lacking any contraindications, such as no tumour at the level of urethral
      dissection. Multimodality bladder-preserving treatment in localised disease is
      currently regarded only as an alternative in selected, well-informed, and
      compliant patients for whom cystectomy is not considered for clinical or personal
      reasons. An appropriate schedule for disease monitoring should be based on (1)
      natural timing of recurrence, (2) probability of disease recurrence, (3)
      functional deterioration at particular sites, and (4) consideration of treatment
      of a recurrence. In metastatic disease, the first-line treatment for patients fit
      enough to sustain cisplatin is cisplatin-containing combination chemotherapy.
      Presently, there is no standard second-line chemotherapy. CONCLUSIONS: These EAU
      guidelines are a short, comprehensive overview of the updated guidelines of (MiM
      BC) as recently published in the EAU guidelines and also available in the
      National Guideline Clearinghouse.

PMID- 19157689
TI  - A longitudinal population-based survey of urinary incontinence, overactive
      bladder, and other lower urinary tract symptoms in women.
AB  - BACKGROUND: Female urinary incontinence (UI), overactive bladder (OAB), and other
      lower urinary tract symptoms (LUTS) are highly prevalent conditions with a
      profound influence on well-being and quality of life. There are a few studies
      describing progression as well as remission, in the short term, of UI in the
      general population as well as in selected groups; at present, there are very few
      population-based studies describing the natural course of other LUTS in the same
      women, and there are no long-term longitudinal studies. OBJECTIVE: To describe
      the prevalence of UI, OAB, and other LUTS in the same women studied prospectively
      over time and, thus, to assess possible progression or regression. DESIGN,
      SETTING, AND PARTICIPANTS: A longitudinal population-based study was performed in
      one primary health care district in the city of Gothenburg, Sweden. The
      participants were a sample of women aged > or = 20 yr who were randomly selected
      from the Swedish National Population Register, assessed in 1991 (n=2911), and
      available for reassessment in 2007 (n=1408). METHODS: A self-administered postal
      questionnaire regarding UI, OAB, and other LUTS was returned by 77% of the
      contacted women in 1991. The same women who responded in 1991 and who were still
      alive and available in the Swedish National Population Register 16 yr later were
      reassessed using a similar self-administered postal questionnaire. RESULTS AND
      LIMITATIONS: In 2007, 1081 of the available 1408 women responded to the
      questionnaire (77%). The overall prevalence of UI, OAB, nocturia, and daytime
      micturition frequency of eight or more times per day increased by 13%, 9%, 20%
      (p<0.001), and 3% (p<0.05), respectively, from 1991 to 2007. The incidence of UI
      and OAB were 21% and 20%, respectively, and the corresponding remission rates
      were 34% and 43%, respectively. Women with OAB symptoms were classified as OAB
      dry or OAB wet, depending on the presence or absence of concomitant UI. The
      prevalence of OAB dry did not differ between the two assessment occasions (11%
      and 10%, respectively), but the prevalence of OAB wet increased from 6% to 16%
      (p<0.001). CONCLUSIONS: UI and other LUTS constitute dynamic conditions. In this
      study, there was a marked overall increase in the prevalence of UI, OAB, and
      nocturia in the same women from 1991 to 2007. Both incidence and remission of
      most symptoms were considerable.

PMID- 19157688
TI  - Salvage therapy with bevacizumab-sunitinib combination after failure of sunitinib
      alone for metastatic renal cell carcinoma: a case series.
AB  - We present a case series of seven patients with metastatic renal cell carcinoma
      treated with bevacizumab (10 mg/kg) in combination with sunitinib 25-50 mg as
      salvage therapy after disease progression under sunitinib monotherapy. Two
      patients had a partial response, four had stable disease, and one patient had
      disease progression. After a median follow-up of 17.2 mo, median progression-free
      survival and overall survival were 8.5 and 15.1 mo, respectively. Two patients
      experienced exacerbation of their preexisting hypertension; there were no grade 4
      toxicities. The bevacizumab-sunitinib combination in sunitinib-refractory
      patients seems active and has a tolerable toxicity profile.

PMID- 19157690
TI  - Aortic atheromas in stroke subgroups detected by multidetector computed
      tomographic angiography.
AB  - BACKGROUND: The aim of this study was to investigate aortic atheromas in stroke
      subgroups. METHODS: Two hundred consecutive subjects had acute ischemic stroke
      confirmed by diffusion-weighted imaging (DWI) (195 cases) or computerized
      tomography (5 cases). Multidetector computed tomographic angiography (MDCTA) (16-
      or 64-slice) was used to detect atherosclerotic plaques in vessels. Patient data
      and diagnostic test results were recorded. Stroke subgroups (TOAST
      classification) were compared with respect to plaque features in the ascending
      aorta or aortic arch such as presence of at least 1 plaque, larger than 1mm
      thick, multiple plaques, and plaque morphology (calcific, soft, mixed and
      ulcerated). RESULTS: Of the patients, 20.3% were in the large-artery
      atherosclerosis (LAA), 29.4% had small artery occlusion (SAO), 23.8% had
      cardioembolism (CE), 6.6% had more than one potential cause found (MPC) and 19.8%
      had cryptogenic stroke (CS). Overall, 49.7% of patients had at least 1 plaque
      (any size) in the ascending aorta or aortic arch. The corresponding rates for
      subgroups were as follows: LAA 80%, SAO 50%, CE 44.7%, MPC 61.5% and CS 20.5%
      (p<0.001). Subgroups also differed significantly with respect to presence of
      multiple plaques and plaques>1mm thick. Of all plaques 93% were mixed type, of
      which 19% were ulcerated. CONCLUSIONS: Almost half of the stroke cases had
      atheroma in ascending aorta or aortic arch and most of them had a soft component.
      Subgroups LAA, SAO, and MPC had higher aortic atheroma density compared to CE and
      CS.

PMID- 19157691
TI  - Application of cotton as a solid phase extraction sorbent for on-line
      preconcentration of copper in water samples prior to inductively coupled plasma
      optical emission spectrometry determination.
AB  - Copper, as a heavy metal, is toxic for many biological systems. Thus, the
      determination of trace amounts of copper in environmental samples is of great
      importance. In the present work, a new method was developed for the determination
      of trace amounts of copper in water samples. The method is based on the formation
      of ternary Cu(II)-CAS-CTAB ion-pair and adsorption of it into a mini-column
      packed with cotton prior applying inductively coupled plasma optical emission
      spectrometry (ICP-OES). The experimental parameters that affected the extraction
      efficiency of the method such as pH, flow rate and volume of the sample solution,
      concentration of chromazurol S (CAS) and cethyltrimethylammonium bromide (CTAB)
      as well as type and concentration of eluent were investigated and optimized. The
      ion-pair (Cu(II)-CAS-CTAB) was quantitatively retained on the cotton under the
      optimum conditions, then eluted completely using a solution of 25% (v/v) 1
      propanol in 0.5 mol L(-1) HNO(3) and directly introduced into the nebulizer of
      the ICP-OES. The detection limit (DL) of the method for copper was 40 ng L(-1)
      (V(sample)=100mL) and the relative standard deviation (R.S.D.) for the
      determination of copper at 10 microg L(-1) level was found to be 1.3%. The method
      was successfully applied to determine the trace amounts of copper in tap water,
      deep well water, seawater and two different mineral waters, and suitable
      recoveries were obtained (92-106%).

PMID- 19157692
TI  - Enhancement of leaching copper by electro-oxidation from metal powders of waste
      printed circuit board.
AB  - Oxidation leaching copper from metal powders of waste printed circuit boards
      (PCBs) was conducted at room temperature in sulfuric acid solution. The result
      showed that the copper in metal powders was oxidized by Cu(2+) to form CuCl(2)(-)
      in the presence of chloride ion without electrochemical oxidation. Then, CuCl(2)(
      ) was oxidized into CuSO(4) by oxygen derived from the air insufflated into
      leaching solution. The leaching rate of copper reached 100%. The whole reaction
      took 5.5h because it was limited by the low solubility of the air in water. In
      the electro-oxidation conditions, the chloride ion was electro-oxidized into ClO(
      ), which oxidized CuCl(2)(-) into CuSO(4) and ClO(-) was reduced into Cl(-)
      itself again at the same time. Since Cl(-) was recycled in the solution not only
      as a complexing agent but also as an oxidant, which made the reaction speed up to
      3.5h to reach 100% leaching rate. Leaching solution was concentrated to
      crystallize CuSO(4).5H(2)O, and crystal liquor was reused to leach copper from
      metal powders.

PMID- 19157693
TI  - Leaching of aluminum and iron from boiler slag generated from a typical Chinese
      Steel Plant.
AB  - This paper presents a new way of recycling aluminum and iron in boiler slag
      derived from coal combustion plants, which integrates efficient extraction and
      reuse of the leached pellets together. The boiler slag was pelletized together
      with washed coal and lime prior to sintering and then was sintered at 800-1200
      degrees C for different periods to produce sintered pellets for the leaching
      test. An elemental analysis of aqueous solutions leached by sulfuric acid was
      determined by EDTA-Na(2)-ZnCl(2) titration method. The components and
      microstructures of the samples, sintered pellets and leached residue were
      examined by means of XRF, XRD and SEM. XRD analysis indicates that predominate
      minerals such as kaolinite, quartz, calcium silicide, hematate and metakoalin
      exist in the boiler slag. An aluminum extraction efficiency of 86.50% was
      achieved. The maximum extraction efficiency of Fe was 94.60% in the same
      conditions of that for the maximum extraction efficiency of Al. The extraction
      efficiencies of Al and Fe increased with an increase in temperature, leaching
      time and acidity. High Al extraction efficiency was obtained for pellets with
      high CaO content. The final product of alumina would be used directly for the
      production of metallic aluminum.

PMID- 19157694
TI  - Multi-walled carbon nanotubes as adsorbents for the removal of parts per billion
      levels of hexavalent chromium from aqueous solution.
AB  - The adsorption capabilities for the removal of parts per billion levels (ppb) of
      hexavalent chromium by three adsorbents namely activated carbon, functionalized
      multi-walled carbon nanotubes (MWCNTs) and unfunctionalized multi-walled carbon
      nanotubes were investigated as a function of contact time, initial solution pH,
      initial Cr(VI) concentrations and the presence of competing anions. The
      unfunctionalized MWCNTs showed the highest adsorption capability with up to 98%
      of a 100 ppb Cr(VI) solution being adsorbed. Both functionalized and non
      functionalized MWCNTs showed a superior adsorption capability to that of
      activated carbon. The removal of Cr(VI) was higher at lower pH. Furthermore, the
      uptake of Cr(VI) was hindered by the presence of the competing anions, Cl(-) and
      SO(4)(2-). Both Langmuir and Freundlich isotherms have been used to describe the
      Cr(VI) adsorption process. The major mechanisms for Cr(VI) removal have been
      identified as an ion exchange mechanism, intraparticle diffusion and
      electrostatic interactions. The adsorbed Cr(VI) could also be desorbed readily
      from the MWCNTs surface at high pH.

PMID- 19157695
TI  - Removal of thiocyanate from aqueous solutions by ion exchange.
AB  - The adsorption kinetics and equilibrium of thiocyanate in aqueous solutions onto
      an anion-exchange resin (Purolite A-250) were investigated in a batch-mode
      operation to assess the possible use of this adsorbent. The effect of various
      parameters such as initial thiocyanate concentration, contact time, pH, particle
      size, resin dosage and temperature were studied. A comparison of four kinetic
      models, the pseudo-first-order, second-order, Elovich and diffusion controlled
      kinetic models, on the thiocyanate-resin system was used to determine the rate
      constants and the adsorption mechanism. The kinetic results correlated well with
      pseudo-second-order model. The experimental parameters had also an effect on the
      pore and surface diffusivities. The optimum conditions for removal of thiocyanate
      were found to be pH 8, 2g/l of adsorbent dosage, 355-500 microm of particle size
      and equilibrium time of 30 min, respectively. The column capacity and performance
      by the bed depth service time model using bed depth and flow rate as variables
      were evaluated. The adsorption isotherm data were fitted well to Langmuir and
      Freundlich isotherms. The adsorption capacity was calculated as 191.20mg/g at 323
      K. Thermodynamics parameters such as free Delta G(0), Delta H(0) and DeltaS(0)
      for the adsorption were evaluated. The positive value of Delta H(0) indicated
      that the process was endothermic in nature.

PMID- 19157696
TI  - Toxic effects of two acid sulfate soils from the Dabaoshan Mine on Corymbia
      citriodora var.variegata and Daphnia carinata.
AB  - Acidic, metal-stressed conditions encountered in the acid sulfate soils
      significantly inhibited the growth of Corymbia citriodora var.variegata, possibly
      due to the reduced rate of photosynthesis and plant root activity. However, the
      plant's self-protection mechanism to counteract stress-induced cellular damage by
      reactive oxygen species still functioned well even at a soil pH as low as 2.81.
      This may explain the high tolerance of this plant species to the extremely acidic
      environments. The observed phytotoxicity symptoms were not accompanied by
      elevated concentrations of heavy metals in the plant tissues, suggesting that
      heavy metal levels in plant tissue alone are not valid indications of
      phytotoxicity to the tested plant species. Leachates from the acid sulfate soils
      had strong toxicity to Daphnia carinata. Median lethal dilution factor (LDF50)
      was much higher for the leachate from the highly acidic acid sulfate soils (ASS)
      than that from the mildly acidic ASS. Although the concentration of various
      metals markedly decreased with increasing number of leaching cycle, leachate
      toxicity to Daphnia carinata did not decrease accordingly. This suggests that
      levels of heavy metals and Al in the leachate are not good indicators of the mine
      water biotoxicity.

PMID- 19157697
TI  - Using tracer technique to study the flow behavior of surfactant foam.
AB  - Surfactant foam was used to remove absorbed hydrocarbons from soils. The nature
      and extent of the foam pathway decide the efficiency of this technology. The
      characteristics and behavior of foam flow are difficult to visually observe. In
      this study, laboratory sandbox experiments were performed to estimate the flow
      behavior of surfactant foam and thus elucidate the properties and flow behavior
      of surfactant foam. To quantitatively determine the distribution of foam and
      evaluate accurately the flow field of foam in the soil, this study designed a
      special technique, applying micro-scale iron powder as a tracer. The foam
      generated with 4% (w/v) mixed solution of Span 60 and sodium dodecyl sulfate
      (SDS) showed an excellent stability and quality, which made it particularly apt
      for this study. The results indicated that the foam flows through the zone above
      the clay planes and also flows through the zone between the clay planes. The
      heterogeneous sand does not inhibit the invasion of foam flow. Moreover, the
      results of tracer tests and photographs of the foam distributions in sandbox were
      identical in the behavior of foam flow. This knowledge is valuable for providing
      insight into the foam remediation of contaminated soil.

PMID- 19157698
TI  - Adsorption of p-nitroaniline from aqueous solutions onto activated carbon fiber
      prepared from cotton stalk.
AB  - Activated carbon fiber prepared from cotton stalk was used as an adsorbent for
      the removal of p-nitroaniline (PNA) from aqueous solutions. Liquid phase
      adsorption experiments were conducted and the maximum adsorptive capacity was
      determined. The effect of experimental parameters such as pH, salinity and
      temperature on the adsorption was studied. The obtained experimental data were
      then fitted with the Langmuir, Freundlich and Redlich-Peterson models to describe
      the equilibrium isotherms. The kinetics rates were modeled by using the pseudo
      first-order and pseudo-second-order equations. The results indicated that cotton
      stalk activated carbon fiber (CS-ACF) is an effective adsorbent for the removal
      of PNA from aqueous solutions. The maximum adsorption capacity of 406 mg g(-1)
      was achieved at the initial PNA concentration of 200 mg L(-1). The optimum pH for
      the removal of PNA was found to be 7.6. The presence of ammonium chloride proved
      to be favorable for the process of adsorption. The adsorption amount decreased
      with increasing temperature. The Redlich-Peterson model was found to best
      represent the equilibrium data. The kinetic data followed closely the pseudo
      second-order equation. Thermodynamic study showed the adsorption was a
      spontaneous exothermic physical process.

PMID- 19157699
TI  - Comparative study on the degradation of I.C. Remazol Brilliant Blue R and I.C.
      Acid Black 1 by Fenton oxidation and Fe 0/air process and toxicity evaluation.
AB  - Degradation of Remazol Brilliant Blue R (anthraquinone dye) and Acid Black 1 (azo
      dye) by Fenton oxidation and low-cost Fe(0)/air process was compared. The doses
      of Fenton reagent needed for decolorization of Remazol Brilliant Blue R was much
      higher than for Acid Black 1. The Fe(0)/air process rapidly decolorized dyes
      within 5 min at the Fe(0) doses of 10 and 50 g L(-1) for Remazol Brilliant Blue R
      and Acid Black 1, respectively. COD removals of Remazol Brilliant Blue R and Acid
      Black 1 by the Fe(0)/air treatment were significantly higher than those by Fenton
      oxidation. 98% COD of Remazol Brilliant Blue R was removed by the Fe(0)/air
      process. The toxicity of Fe(0)/air-treated solution was significantly lower than
      that of Fenton-treated solution; no toxicity was detected after the treatment of
      Remazol Brilliant Blue R by the Fe(0)/air process. Fe(0)/air technique is a
      potential process for dye degradation.

PMID- 19157700
TI  - Metal removal by bed filter materials used in domestic wastewater treatment.
AB  - Bed filters using reactive materials are an emerging technology for on-site
      wastewater treatment. Used materials, which are enriched with phosphorus, can be
      used as a fertiliser or soil amendment. However the materials can also be
      enriched with metals from the wastewater. Six materials (opoka, sand, Polonite,
      limestone, two types of blast furnace slag) exposed to long-term wastewater
      loading in columns and in a compact filter well filled with Polonite were
      investigated for metal removal and accumulation. Wastewater applied to the
      columns had low heavy metal concentrations in the order Zn>Cu>Mn>Ni>Cr. All
      columns were able to remove 53%-83% of Zn except those filled with sand. Polonite
      demonstrated a high removal capacity of Mn (>98%), while only the slag materials
      were able to remove Ni. All materials showed increased Cu, Cr(III), Mn, Pb and Zn
      content after filtration. Speciation calculations showed that high concentrations
      of dissolved organic matter might have prevented efficient metal removal,
      particularly in the case of Cu. The low content of toxic heavy metals in the
      studied filter materials studied would probably not restrict their use as a
      fertiliser or soil amendment.

PMID- 19157701
TI  - Copper removal from oil-field brine by coprecipitation.
AB  - The present study aims at investigation of copper removal from oil-field brine by
      coprecipitation process. The produced brine containing heavy metals is usually
      returned to the reservoir for water flooding or is discarded to the surroundings.
      Therefore, surface waters or underground waters may be polluted due to probable
      contact to these discarded waters. Removal experiments were carried out at room
      temperature in a bench-scale crystallizer equipped with a draft tube. In order to
      gain an insight into the influence of soluble compounds in the industrial natural
      brine on the precipitation process, some comparative experiments were performed
      both on a sample of natural brine and on a synthetic simulated brine in the
      absence of natural impurities. A metal removal practice by coprecipitation of
      copper through CaCO(3) precipitates induced by reaction of Na(2)CO(3) and CaCl(2)
      reduced the copper concentration (Cu(2+)) from 0.27 ppm in the synthetic brine to
      0.06 ppm. This removal of 78% required only 1g of precipitate per 0.15 mg copper
      metal. Analysis of the experimental results suggested that about 5% of the copper
      removal from the synthetic brine was through the mechanism of incorporation into
      the crystal lattice, and around 95% was through the adsorption on the crystal
      faces.

PMID- 19157702
TI  - Preconcentration of Zn(II) in water samples using a new hybrid SBA-15-based
      material.
AB  - A SBA-15 mesoporous silica has been chemically modified with 5-mercapto-1
      methyltetrazole. The newly synthesized material (MTTZ-SBA-15) has been
      characterized, by powder X-ray diffraction, N(2) adsorption, FT-IR, (13)C NMR
      spectroscopy and elemental analysis, and used to preconcentrate Zn(II) in water
      samples. The effect of some variables on the adsorption capacity has been studied
      using the column techniques. The adsorption capacity of the prepared material
      followed the order: Zn>>Cu>Cd>>Mn, and under optimized conditions the maximum
      adsorption value for Zn(II) was 0.96+/-0.01 mmol/g with the adsorption efficiency
      of 0.76. In column experiments, adsorption was quantitative for 1000 mL of 7.65 x
      10(-4)mM of Zn(II) solution and adsorbed ions were eluted out by 5 mL of 1M HCl
      (preconcentration factor of 200). Spiked tap water and mineral water were used
      for the preconcentration and determination of Zn(II) by flame atomic absorption
      spectrometry (FAAS), and a 102+/-2 and 98+/-3% recoveries were obtained. The LOD
      and LOQ values of the proposed method were found to be 8.0 x 10(-6) and 1.23 x
      10(-5)mM, respectively. The relative standard deviation for four preconcentration
      experiments was found to be <or=4% in all cases.

PMID- 19157703
TI  - Co(II) removal by magnetic alginate beads containing Cyanex 272.
AB  - In this study, a series of batch experiments is conducted to investigate the
      ability of magnetic alginate beads containing Cyanex 272 to remove Co(II) ions
      from aqueous solutions. Equilibrium sorption experiments show a Co(II) uptake
      capacity of 0.4 mmol g(-1). The data are successfully modelled with a Langmuir
      equation. A series of kinetics experiments is then carried out and a pseudo
      second order equation is used to fit the experimental data. The effect of pH on
      the sorption of Co(II) ions is also investigated. Desorption experiments by
      elution of the loaded beads with nitric acid at pH 1 show that the magnetic
      alginate beads could be reused without significant losses of their initial
      properties even after 3 adsorption-desorption cycles.

PMID- 19157704
TI  - Degradation of fuel oil in salt marsh soils affected by the Prestige oil spill.
AB  - We assessed natural degradation of fuel oil in three marshes from Galicia (Spain)
      affected by the Prestige oil spill (Baldaio, Barizo, and Muxia). Soil samples
      collected from polluted and unpolluted areas on four different dates were used to
      determine total petroleum hydrocarbon content and fuel-oil components. Natural
      degradation was monitored by analysing changes in the proportion of saturated
      hydrocarbons, aromatics, asphaltenes and resins in the soils, and also by
      evaluating the degree of depletion of saturated hydrocarbons on each sampling
      date. We additionally assessed the phytoremediation potential of Lolium perenne,
      L., Convolvulus arvensis L. and Raphanus raphanistrum L. All marsh soils
      exhibited natural degradation of saturated and aromatic hydrocarbons to between
      85 and 95% in most cases. In contrast, asphaltenes and resins were degraded to a
      lesser extent (viz. 64-76% in Barizo 1, Muxia and Traba; 39-44% in Baldaio; and
      only 12% in Barizo 2, where flooding by the river continues to introduce balls of
      fuel oil into the soil). Monitoring analyses revealed natural degradation to be
      dependent on the thickness of the pollutant layer. Field plots sown with L.
      perenne L. exhibited no significant differences in fuel-oil degradation from
      untreated plots.

PMID- 19157705
TI  - Phycoremediation of Chromium (VI) by Nitella and impact of calcium encrustation.
AB  - This article discusses the applicability of the Charophyte, Nitella
      pseudoflabellata in the remediation of Cr (VI) contaminated waters at different
      calcifying potentials. Its growth was found to be positively correlated with Ca
      in water (CaW), but marginally significant in the presence of Cr (VI) in water
      (CrW). High CaW resulted in calcite encrustation on the plant cell wall. CaW was
      found to be aiding Cr (VI) fixation in the long run, as this correlated
      positively with both CaW and CrW. However, Ca interfered with passive Cr (VI)
      accumulation in live plant matter at low CrW concentrations (<or=0.2mg/L).
      Biosorption by dead plant matter seemed to be the major mechanism as the dead
      plant organs contained >1mg/g Cr dry weight of plant. Cr (VI) concentrations
      greater than 0.4 mg/L were too toxic, showing maximum quantum efficiency of PSII
      photochemistry (F(v)/F(m)) values<0.63. The opposite was noticed (F(v)/F(m)>0.76)
      when Cr (VI) was less than 0.2mg/L. Elongation curve patterns based on shoot
      lengths showed similar scenarios. In all cases high CaW units with calcite
      encrustation found to be least affected by Cr (VI) toxicity. Optimum remediation
      was obtained using a combination of high Ca and Cr (VI) in the case of passive
      (short-term) operation and low Ca and Cr (VI) for active (long-term) operation.
      Under the passive scenario, plants accumulated above 1.2mg/g Cr dry weight
      whereas in the active case, accumulation was 0.8 mg/g Cr dry weight. We conclude
      that Nitella-mediated Cr (VI) remediation is a promising technique within the
      range and conditions investigated.

PMID- 19157706
TI  - Retention of copper originating from different fungicides in contrasting soil
      types.
AB  - This work described the retention of Cu from two different commonly used
      pesticides, the Bordeaux mixture (CuSO(4)+Ca(OH)(2)) and Cu-oxychloride
      (3Cu(OH)(2).CuCl(2)), and from Cu(NO(3))(2) in contrasting soil types (Leptosol,
      Chernozem, Cambisol). Thermodynamic modeling showed that Cu speciation was
      similar in all fungicide solutions. However, the retention of Cu differed with
      the fungicide used (maximum retention from the Bordeaux mixture) which indicates
      that different retention processes occurred in the studied soils. The suggested
      mechanisms include: specific and non-specific adsorption (especially on soil
      organic matter), precipitation of newly formed phases, such as CuO, Cu(OH)(2),
      Cu(2)(OH)(3)NO(3), CuCO(3)/Cu(2)(OH)(2)CO(3) and in the case of the Bordeaux
      mixture, precipitation of various Cu-hydroxysulfates. These phases were
      identified by the speciation model. The retention of fungicide-derived Cu in the
      studied soil types followed well the Freundlich isotherm and was directly
      controlled by the chemical form of Cu. This fact should be taken into account for
      both environmental and practical applications.

PMID- 19157707
TI  - Adsorption characteristics of anionic nutrients onto the PP-g-AA-Am non-woven
      fabric prepared by photoinduced graft and subsequent chemical modification.
AB  - PP-g-AA-Am non-woven fabric, which possesses anionic exchangeable function, was
      prepared by chemical modification of carboxyl group in PP-g-AA non-woven fabric
      to amine group using diethylene triamine. Its sorption characteristics for
      anionic nutrients including isotherm, kinetics, effects of pH and co-anions, and
      regeneration efficiency were studied by batch sorption experiments. Sorption
      equilibriums of PO(4)-P on PP-g-AA-Am fabric were well described by the Langmuir
      isotherm model, and their sorption energies were ranged between 9.94 and 15.96
      kJ/mol indicating an ion exchange process as primary sorption mechanism. Sorption
      kinetic data fitted with pseudo-second-order kinetic model and indicated that
      both external and intraparticle diffusion took part in sorption processes. The
      uptake of PO(4)-P by PP-g-AA-Am fabric increased with increasing pH of solution
      and its optimum pH region was in pH >or=4, whereas the uptake of NO(3)-N and
      NO(2)-N was higher in weak and strong acidic pH region, respectively. The
      sorption selectivity for anions by PP-g-AA-Am fabric was increased in the order:
      SO(4)>or=PO(4)>NO(3)>Cl. The PP-g-AA-Am fabric could be regenerated by a simple
      acid washing process without lowering the sorption capacity or physical
      durability.

PMID- 19157708
TI  - Decolorization and biodegradation of textile dye Navy blue HER by Trichosporon
      beigelii NCIM-3326.
AB  - Navy blue HER was decolorized and degraded within 24h by Trichosporon beigelii
      NCIM-3326 under static condition. In the present study, we investigated various
      physicochemical parameters such as agitation, temperature, pH, cell
      concentration, initial dye concentration and different carbon and nitrogen
      sources to achieve maximum dye degradation by T. beigelii. Sequentially,
      decolorization and decrease in the total organic carbon (TOC) of Navy blue HER by
      T. beigelii were measured. Among five strains T. beigelii gave the better
      performance on the decolorization of Navy blue HER along with a 95% TOC reduction
      within 24h. A significant increase in the activities of NADH-DCIP
      (dichlorophenolindophenol) reductase and azoreductase in the cells obtained after
      complete decolorization presumably indicates involvement of these enzymes in
      decolorization process. UV-vis, TLC, HPLC and FTIR analysis of extracted products
      confirmed the biodegradation of Navy blue HER. Phytotoxicity study demonstrated
      no toxicity of the biodegraded products with respect to plants viz. Phaseolus
      mungo and Sorghum vulgare. In addition to Navy blue HER, this strain also shows
      ability to decolorize various industrial dyes, including Red HE7B, Golden yellow
      4BD, Green HE4BD, Orange HE2R, Malachite green, Crystal violet and Methyl violet.

PMID- 19157709
TI  - Prediction of detonation performance of CHNO and CHNOAl explosives through
      molecular structure.
AB  - A new pathway has been introduced to predict detonation pressure of CHNO and
      CHNOAl explosives. Although aluminized explosives can have Chapman-Jouguet
      detonation performance significantly different from those expected from existing
      thermodynamic computer codes for equilibrium and steady state calculations, new
      correlation can also be used here. Molecular structures of CHNO and CHNOAl
      explosives are the only necessary parameters that would be needed in this new
      scheme. There is no need to use heat of formation or any experimental data.
      Besides, elemental compositions of CHNO and CHNOAl explosives rather than assumed
      detonation products are essential input parameters. Predicted detonation
      pressures for CHNO explosives are compared with experimental data as well as
      computed results gained by complicated computer code using BKWR and BKWS
      equations of state so the new method shows the best results. Also, the calculated
      results for CHNOAl explosives indicate good agreement with the measured data as
      compared to estimated results of BKWS-EOS using full and partial equilibrium.

PMID- 19157710
TI  - Maternal family history of hypertension attenuates neonatal pain response.
AB  - Reduced sensitivity to naturally occurring and laboratory pain stimuli has been
      observed in individuals with hypertension, high-normal blood pressure, and a
      family history of hypertension. The present study sought to extend these findings
      by examining the relationship between familial history of hypertension and pain
      responsivity in neonates. Eighty infants had intramuscular (IM) injections of
      vitamin K performed in the delivery room within 1h of birth as per institutional
      practice. Video recordings of the injection procedure were used by trained
      observers to code infant pain responses using facial grimacing and cry duration.
      Prior to the birth of the child, the infants' parents each completed a family
      blood pressure history survey and these responses were used to identify infants
      with and without a maternal and paternal family history of hypertension. As
      compared to infants without a maternal family history of hypertension, infants
      with a maternal family history of hypertension had significantly shorter crying
      times, F(1,74)=6.96, p=.01, eta(2)=.086, and marginally lower facial grimacing
      scores, F(1,74)=2.68, p=.10, eta(2)=.035, during vitamin K injection. The
      presence of attenuated responses to the IM injection in neonates with a maternal
      family history of hypertension provides important and novel evidence that reduced
      pain responding in individuals at risk for hypertension is not a learned response
      style, but rather may arise from prenatal or genetic influences.

PMID- 19157712
TI  - First record in South America of Koellikerioides internogastricus (Digenea,
      Didymozoidae) with new host record and pathological alterations.
AB  - The study of different species of tunas has revealed high numbers of cysts of
      Koellikerioides internogastricus Yamaguti, 1970, parasitizing Thunnus atlanticus
      (Lesson), Thunnus albacares (Bonnaterre) and Thunnus obesus (Lowe), caught along
      the Rio de Janeiro coastline, Atlantic Ocean, Brazil. This parasite was isolated
      from mucosa and submucosa of the stomach of the three tuna species studied. We
      report K. internogastricus for the first time on the Brazilian coast,
      representing the first record of this species in South America and in T.
      atlanticus, a new host. The pathological alterations induced by K.
      internogastricus in the stomach of T. albacares, T. atlanticus and T. obesus are
      also described for the first time. Original measurements and figures are
      presented.

PMID- 19157711
TI  - Practical factors affecting the performance of a thin-film phase plate for
      transmission electron microscopy.
AB  - A number of practical issues must be addressed when using thin carbon films as
      quarter-wave plates for Zernike phase-contrast electron microscopy. We describe,
      for example, how we meet the more stringent requirements that must be satisfied
      for beam alignment in this imaging mode. In addition we address the concern that
      one might have regarding the loss of some of the scattered electrons as they pass
      through such a phase plate. We show that two easily measured parameters, (1) the
      low-resolution image contrast produced in cryo-EM images of tobacco mosaic virus
      particles and (2) the fall-off of the envelope function at high resolution, can
      be used to quantitatively compare the data quality for Zernike phase-contrast
      images and for defocused bright-field images. We describe how we prepare carbon
      film phase plates that are initially free of charging or other effects that
      degrade image quality. We emphasize, however, that even though the buildup of
      hydrocarbon contamination can be avoided by heating the phase plates during use,
      their performance nevertheless deteriorates over the time scale of days to weeks,
      thus requiring their frequent replacement in order to maintain optimal
      performance.

PMID- 19157714
TI  - Prenatal stress exacerbates the impact of an aversive procedure on the
      corticosterone response to stress in female rats.
AB  - Post-traumatic stress disorder (PTSD) is associated with marked alterations in
      hypothalamic-pituitary adrenal (HPA) function. In rats, prenatal restraint stress
      (stress applied to pregnant mothers, PRS) is known to impact behavioral and
      neuroendocrine sensitivity to several kinds of mild stress in adulthood. We have
      recently shown that PRS also modifies behavioral responses after exposure to an
      intense footshock in a potential animal model of PTSD. The aim of the present
      study was to evaluate the long-term effects of an aversive procedure (footshock
      followed by 3 weekly situational reminders) on the corticosterone response to a
      novel stress (restraint stress, 140 days after the footshock) in adult female PRS
      rats. Our data extend previous results showing that PRS leads to a long-lasting
      increase in plasma corticosterone after restraint stress in adult male rats.
      Moreover, we demonstrate that 140 days after the intense footshock, female PRS
      rats have lower corticosterone levels 60 min after restraint stress, suggesting
      an increase in the negative feedback of the HPA axis. These results indicate that
      early stress may favor long-lasting modifications of the HPA axis subsequent to
      exposure to an intense stress in adulthood.

PMID- 19157715
TI  - Pre-quit depression level and smoking expectancies for mood management predict
      the nature of smoking withdrawal symptoms in college women smokers.
AB  - We assessed smoking withdrawal symptoms over a six-day period of abstinence among
      21 female college students who were daily cigarette smokers [M=20.3 (4.4);
      cigarettes per day] and were in the preparation stage of change for quitting
      smoking. We predicted that reported withdrawal symptoms would covary with
      baseline depression scores and baseline outcome expectancies for cigarette
      smoking as a mood management tool. Depression scores at baseline significantly
      predicted mood-related smoking withdrawal symptoms of Depression-Dejection and
      Vigor from the Profile of Mood States (POMS). Smoking outcome expectancies for
      relief of negative affect measured at baseline significantly predicted symptoms
      of Confusion-Bewilderment and Anger-Hostility. Neither baseline depression nor
      baseline smoking expectancies for mood management predicted smoking withdrawal
      symptoms measured by the Smoking Withdrawal Questionnaire (SWQ; [Shiffman, S. M.,
      & Jarvik, M. E. (1976). Smoking withdrawal symptoms in two weeks of abstinence.
      Psychopharmacology, 50, 35-39]). Results imply that women smokers with baseline
      depressive symptomatology and expectancies for smoking to relieve negative mood
      endure greater abstinence-induced mood disturbance, but similar levels of other
      smoking withdrawal symptoms during initial abstinence. These results may inform
      smoking cessation efforts.

PMID- 19157716
TI  - Testing the Cigarette Dependence Scale in 4 samples of daily smokers: psychiatric
      clinics, smoking cessation clinics, a smoking cessation website and in the
      general population.
AB  - AIM: To assess the properties of the Cigarette Dependence Scale (CDS-12) in
      various samples of daily smokers and to provide reference scores in a general
      population sample. METHODS: Surveys in 4 samples of daily cigarette smokers:
      psychiatric out-patients in Geneva, Switzerland (n=226), clients of smoking
      cessation clinics in France (n=370), visitors of a French-language smoking
      cessation website (n=13,697) and a representative sample of the general
      population of Geneva (n=292). RESULTS: In all 4 samples, Cronbach's alpha
      coefficients were >0.87 and factor analyses indicated that CDS-12 was
      unidimensional. CDS-12 was slightly skewed towards higher values, and it was
      associated with expired carbon monoxide, but this association was not strong (9%
      of variance explained, p<0.001). CDS-12 scores were highest in clients of smoking
      cessation clinics (mean=47.7, SD=10.2), followed by psychiatric patients
      (mean=44.4, SD=8.4), visitors of smoking cessation websites (mean=43.3, SD=11.6)
      and the general population sample (mean=36.9, SD=12.3). Except for tolerance,
      each element in the DSM-IV and ICD-10 definitions of dependence is reflected by
      at least one item in CDS-12, even though the match with these definitions is
      sometimes indirect. CONCLUSIONS: This paper presents reference scores and
      validity and reliability tests for CDS-12 in a diversity of samples of daily
      smokers. This information should be useful to clinicians and researchers.

PMID- 19157717
TI  - Methodological issues in evaluating environmental risk factors: a response to
      Ivanovski et al.

PMID- 19157718
TI  - A new concept for an old system: the anti-inflammatory paradigm of the renin
      angiotensin system.
AB  - The renin-angiotensin system (RAS) is classically known as a regulator of
      arterial pressure, which is accomplished by regulating the balance of water and
      sodium. This has led to the successful development of drugs such as anti
      hypertensives that block the system. In addition, this system has a fundamental
      role in the mechanisms of inflammation and of defense for the cells and tissues
      of organisms. This last function is fulfilled by regulating oxidative stress at
      the cytoplasmic and mitochondrial level. From an evolutionary standpoint, this
      effect came before it began its role as a regulator of arterial pressure. If we
      were to consider cardiovascular disease as being inflammatory, then beyond its
      anti-hypertensive effect, RAS's blockade of this phenomenon could be seen as an
      etiologic treatment of cardiovascular disease.

PMID- 19157719
TI  - The subthalamic nucleus is a key-structure of limbic basal ganglia functions.
AB  - Among the basal ganglia nuclei, the subthalamic nucleus has a major function in
      the motor cortico-basal ganglia-thalamo-cortical circuit and is a target site for
      neurosurgical treatment such as parkinsonian patients with long-term motor
      fluctuations and dyskinesia. According to animal and human studies, the motor
      functions of the subthalamic nucleus have been well documented whereas its
      implication on limbic functions is still less well understood and is only
      partially explained by anatomical and functional theories of basal ganglia
      organisation. After chronic subthalamic nucleus stimulation in patients with
      Parkinson's disease, many studies showed executive impairments, apathy,
      depression, hypomania, and impairment of recognition of negative facial emotions.
      The medial tip of the subthalamic nucleus represents its limbic part. This part
      receives inputs from the anterior cingulate cortex, the medial prefrontal cortex,
      the limbic part of the striatum (nucleus accumbens), the ventral tegmental area
      and the limbic ventral pallidum. The medial tip of the subthalamic nucleus
      projects to the limbic part of the substantia nigra and the ventral tegmental
      area. We propose a new function scheme of the limbic system, establishing
      connections between limbic cortical structures (medial prefrontal cortex,
      amygdala and hippocampus) and the limbic part of the basal ganglia. This new
      circuit could be composed of a minor part based on the model of cortico-basal
      ganglia-thalamo-cortical loop, and of a major part linking the subthalamic
      nucleus with the mesolimbic dopaminergic pathway via the ventral tegmental area
      and the nucleus accumbens, and with limbic cortical structures. This scheme could
      explain limbic impairments after subthalamic nucleus stimulation by disruption of
      limbic information inside the subthalamic nucleus and the ventral tegmental area.

PMID- 19157720
TI  - Heterogeneity of angiogenesis and blood vessel maturation in cartilage tumors.
AB  - Cartilage tumors have a special angiogenic phenotype, with blood vessels arranged
      predominantly in pericartilage fibrous septa and relatively low microvessel
      density (MVD), except in dedifferentiated chondrosarcomas. To further elucidate
      angiogenesis in cartilage tumors, we used double-labeling immunohistochemistry to
      determine microvessel pericyte coverage index (MPI) and proliferating capillary
      index (PCI), referring to blood vessel maturation and angiogenic activity in
      enchondromas, conventional chondrosarcomas, and dedifferentiated chondrosarcomas.
      Altogether, we found high MPIs (>70%) especially in dedifferentiated
      chondrosarcomas but without a correlation to the grade of malignancy. PCI was
      significantly higher in conventional chondrosarcomas grades II and III than in
      enchondromas, chondrosarcomas grade I, and dedifferentiated chondrosarcomas.
      Thus, PCI positively correlated with the previously reported differential
      expression of vascular endothelial growth factor (VEGF)-A in cartilage tumors.
      Altogether, cartilage tumors exhibit a heterogeneous but predominantly mature
      angiogenic phenotype with differential proliferative activity.

PMID- 19157721
TI  - Treatment parameters and outcome in 680 treatments of internal radiation with
      resin 90Y-microspheres for unresectable hepatic tumors.
AB  - PURPOSE: Radioembolization (RE) using (90)Y-microspheres is an effective and safe
      treatment for patients with unresectable liver malignancies. Radiation-induced
      liver disease (RILD) is rare after RE; however, greater understanding of
      radiation-related factors leading to serious liver toxicity is needed. METHODS
      AND MATERIALS: Retrospective review of radiation parameters was performed. All
      data pertaining to demographics, tumor, radiation, and outcomes were analyzed for
      significance and dependencies to develop a predictive model for RILD. Toxicity
      was scored using the National Cancer Institute Common Toxicity Criteria Adverse
      Events Version 3.0 scale. RESULTS: A total of 515 patients (287 men; 228 women)
      from 14 US and 2 EU centers underwent 680 separate RE treatments with resin (90)Y
      microspheres in 2003-2006. Multifactorial analyses identified factors related to
      toxicity, including activity (GBq) Selective Internal Radiation Therapy delivered
      (p < 0.0001), prescribed (GBq) activity (p < 0.0001), percentage of empiric
      activity (GBq) delivered (p < 0.0001), number of prior liver treatments (p <
      0.0008), and medical center (p < 0.0001). The RILD was diagnosed in 28 of 680
      treatments (4%), with 21 of 28 cases (75%) from one center, which used the
      empiric method. CONCLUSIONS: There was an association between the empiric method,
      percentage of calculated activity delivered to the patient, and the most severe
      toxicity, RILD. A predictive model for RILD is not yet possible given the large
      variance in these data.

PMID- 19157722
TI  - [Efficacy of a multidisciplinary team for preventing hospital-acquired invasive
      aspergillosis: five years' experience].
AB  - Invasive hospital-acquired aspergillosis (IA) is responsible for lethal
      outbreaks. In 2002, an interdisciplinary team was created in the teaching
      hospital of Rouen in order to organize the surveillance of construction sites by
      the implementation of environmental measures of prevention. The aim of our study
      was to estimate the efficiency of these measures using an indirect indicator,
      reflecting the incidence of the cases of invasive nosocomial aspergillosis (AI):
      the consumption of antifungals. From the nominative prescriptions established, we
      studied the medical files about 210 patients to track down the number of IA cases
      in intensive care unit (ICUI) and in pediatric hematology-oncology units between
      2002 and 2006. The incidence of the cases was put in parallel with the various
      periods of level 5-risk works during these five years. The relative risk of
      appearance of the disease was calculated. In pediatric haematology-oncology unit,
      35 cases were diagnosed on 99 medical files which have been studied and in ICU 19
      cases were classified on 93 studied files. The follow-up of the incidence in both
      units stake in parallel with the periods of level 5-risk works does not show
      increase of the number of cases. The calculated relative risk indicates the same
      result: the level 5-risk works are not a factor facilitating the appearance of
      invasive aspergillosis cases. This study shows the importance of the
      environmental measures of prevention during the periods of works within services
      for risk. The coordination of the actors within an interdisciplinary cell seems
      thus essential for the prevention of AIN.

PMID- 19157724
TI  - Polymorphism in glutathione-S-transferases: a risk factor in alcoholic liver
      cirrhosis.
AB  - In a case-control study, association of polymorphism in glutathione-S
      transferases (GSTM1, GSTT1, GSTP1), involved in detoxification of reactive oxygen
      species (ROS), was studied with alcoholic liver cirrhosis. The study included 175
      alcoholic cirrhotic patients (ACPs), 140 non-alcoholic cirrhotic patients
      (NACPs), visiting Sanjay Gandhi Post Graduate Institute of Medical Sciences
      (SGPGI), Lucknow, India, 255 non-alcoholic controls and 140 alcoholic controls.
      The data showed an increase in risk to alcoholic cirrhosis in ACPs with GSTM1
      (null) genotype when compared with non-alcoholic controls (OR: 1.7; 95% CI: 1.15
      2.56) or alcoholic controls (OR: 1.7; 95% CI: 1.07-2.73). Significant increase in
      risk was also observed in ACPs with variant genotype of GSTP1 when compared with
      non-alcoholic controls (OR: 1.65; 95% CI: 1.12-2.43). A much higher risk to
      alcoholic liver cirrhosis was observed in patients carrying combination of null
      genotypes of GSTM1 and GSTT1 (OR: 2.8; 95% CI: 1.3-6.06) or variant genotype of
      GSTP1 and null genotype of GSTM1 (OR: 2.8; 95% CI: 1.58-4.90) or GSTT1 (OR: 2.16;
      95% CI: 1.08-4.28). Likewise, greater risk for alcoholic cirrhosis was observed
      in patients carrying combination of GSTM1, GSTT1 (null) and variant genotype of
      GSTP1 (OR: 5.8; 95% CI: 2.17-15.80). Our data further showed that interaction of
      GSTs with variant genotype of manganese superoxide dismutase (MnSOD), which
      detoxifies free radicals, or cytochrome P450 2E1, which generates free radicals,
      resulted in several fold increase in risk to alcoholic liver cirrhosis in ACPs
      when compared with non-alcoholic controls thus demonstrating the role of gene
      gene interactions in modulating the risk to alcoholic liver cirrhosis.

PMID- 19157723
TI  - Construct, concurrent and predictive validity of the URICA: data from two multi
      site clinical trials.
AB  - BACKGROUND: A better understanding of how to measure motivation to change and how
      it relates to behavior change in patients with drug and alcohol dependence would
      broaden our understanding of the role of motivation in addiction treatment.
      METHODS: Two multi-site, randomized clinical trials comparing brief motivational
      interventions with standard care were conducted in the National Institute on Drug
      Abuse Clinical Trials Network. Patients with primary drug dependence and alcohol
      dependence entering outpatient treatment participated in a study of either
      Motivational Enhancement Therapy (n=431) or Motivational Interviewing (n=423).
      The construct, concurrent, and predictive validity of two composite measures of
      motivation to change derived from the University of Rhode Island Change
      Assessment (URICA): Readiness to Change (RTC) and Committed Action (CA) were
      evaluated. RESULTS: Confirmatory factor analysis confirmed the a priori factor
      structure of the URICA. RTC was significantly associated with measures of
      addiction severity at baseline (r=.12-.52, p<.05). Although statistically
      significant (p<.01), the correlations between treatment outcomes and RTC were low
      (r=-.15 and -18). Additional analyses did not support a moderating or mediating
      effect of motivation on treatment retention or substance use. CONCLUSIONS: The
      construct validity of the URICA was confirmed separately in a large sample of
      drug- and alcohol-dependent patients. However, evidence for the predictive
      validity of composite scores was very limited and there were no moderating or
      mediating effects of either measure on treatment outcome. Thus, increased
      motivation to change, as measured by the composite scores of motivation derived
      from the URICA, does not appear to influence treatment outcome.

PMID- 19157725
TI  - Molecular characterisation of Staphylococcus aureus strains isolated from small
      and large ruminants reveals a host rather than tissue specificity.
AB  - Staphylococcus aureus is an important pathogen in domestic ruminants. The main
      objective of this study was to determine the similarity of epidemiologically
      unrelated S. aureus isolates from bovine, ovine, and caprine hosts regardless the
      locus of isolation (nares and udder). By pulsed-field gel electrophoresis, seven
      major pulsotypes were identified among 153 isolates recovered from 12 different
      regions of France as well as from Brazil, the USA and Belgium. Typing of the
      accessory gene regulator (agr) and capsular (cap) serotype was carried out on all
      the isolates and revealed the predominance of agr I and III and of cap8
      regardless the ruminant host species. Screening for methicilin-resistant S.
      aureus (MRSA) was carried out by disk diffusion and revealed a prevalence of only
      3.2% of MRSA among the strains tested. These results suggest the existence of a
      host rather than tissue specificity among S. aureus isolates colonising the
      ruminant species and suggest a limited transmission of those isolates between
      large (bovine) and small (ovine-caprine) ruminants. The agr class and cap types
      correlated with pulsotype clusters rather than with a specific host species.
      Antimicrobial resistance appears not to have contributed to the predominance of
      any given genotypes, and MRSA prevalence appears very low in ruminant isolates.

PMID- 19157726
TI  - A multiplex PCR for toxin typing of Clostridium perfringens isolates.

PMID- 19157727
TI  - Field and laboratory evidence that Bungowannah virus, a recently recognised
      pestivirus, is the causative agent of the porcine myocarditis syndrome (PMC).
AB  - In 2003 an outbreak of sudden deaths occurred in 2-3-week-old piglets on a
      piggery in New South Wales, Australia. There was a marked increase in the birth
      of stillborn piglets and preweaning losses associated with a multifocal non
      suppurative myocarditis with myonecrosis. The aim of this study was to review
      existing data and to undertake further investigations of specimens from naturally
      infected pigs to provide evidence to support the hypothesis that Bungowannah
      virus, a recently recognised pestivirus, causes the porcine myocarditis syndrome
      (PMC). Sera collected from gilts and sows from affected and unaffected units were
      tested for Bungowannah virus antibody by a peroxidase-linked assay and
      Bungowannah virus RNA by qRT-PCR in selected cases. Stillborn piglets from
      affected and an unaffected unit were also tested for Bungowannah virus antibody
      and RNA. Body fluid IgG levels and the incidence of myocardial lesions in these
      stillborn piglets are summarised. Tissue sections from stillborn piglets with
      myocarditis/myonecrosis were examined for Bungowannah virus RNA by in situ
      hybridisation. A clear temporal association between the occurrence of PMC on a
      unit or module and exposure to Bungowannah virus was identified by serological
      tests in both breeding aged animals and stillborn pigs. In addition, at the
      individual animal level on affected units, Bungowannah virus RNA was detected in
      stillborn piglets in large amounts by qRT-PCR and in association with myocardial
      lesions by in situ hybridisation. The examination of field material from cases of
      PMC by serology, qRT-PCR and in situ hybridisation provides strong indirect
      evidence that Bungowannah virus is the causative agent for PMC.

PMID- 19157728
TI  - Prion protein genotypes of Italian sheep breeds with lysine-171 and phenylalanine
      141 detection.
AB  - Amino acid polymorphisms of the prion protein gene influence sheep susceptibility
      to classical and atypical scrapie. Substitutions at codons 136, 154 and 171 play
      an important role in classical scrapie. Codon 141 leucine to phenylalanine
      mutation (AFRQ) has been recognized as an increased risk factor for atypical
      scrapie. In addition a rare allele with lysine at codon 171 (ARK) has been
      detected in Mediterranean sheep breeds. The presence of ARK poses two problems:
      the determination of its frequency and its possible interference with genotyping
      output of routine methods lacking specific detection capacity for ARK. The aim of
      our work was the development of a routine genotyping method with the capacity to
      identify ARK and AFRQ in addition to the normally detected alleles and to
      determine the frequencies of all these alleles in 5 main Italian breeds: Sarda
      (n=2494), Bergamasca (n=2686), Appenninica (n=297), Comisana (n=361) and Massese
      (n=402). A multiplex primer extension assay targeting the six single nucleotide
      polymorphisms of interest was developed. Allele frequencies revealed a very low
      level of ARR in Bergamasca (6.91%) as opposed to the other breeds, very diverse
      levels of AFRQ ranging from absence in Comisana to 10.70% in Massese and a
      restricted presence of ARK. This allele has only been detected in Bargamasca with
      a significant 3.67% and marginally in Appenninica (0.34%). These results
      underline the need for adequate routine methods for genotyping of breeds with
      alleles that can interfere with typing of important codons such as the case of
      ARK for codon 171.

PMID- 19157729
TI  - Season of the year influences semen output and concentrations of testosterone in
      circulation of yaks (Poephagus grunniens L.).
AB  - Seasonal changes in plasma testosterone concentration and semen quality were
      evaluated in yak bulls throughout a 1-year period. Blood samples were collected
      every week from adult yak bulls (n=15). These blood samples were analyzed for
      testosterone using a highly sensitive enzyme-linked immunoassay. Ejaculates were
      collected from five representative bulls each week. Ejaculate volume, progressive
      motility, live sperm count and sperm concentrations were determined. Mean
      testosterone in plasma was 1.03+/-0.25 ng/ml. Concentrations of testosterone
      changed throughout the year (P<0.05) and were found to be highest during the
      winter. It was also higher during the autumn than in summer and spring (P<0.05).
      Mean ejaculate volume, progressive motility, live sperm count and spermatozoa
      concentration were 2.7+/-0.3 ml, 72.8+/-1.4%, 82.3+/-0.9% and 968+/-233 x
      10(6)ml(-1), respectively. Ejaculate volume and sperm concentration were higher
      (P<0.05) in autumn than in other seasons. To conclude, a highly sensitive EIA for
      testosterone was developed and validated for yak plasma. Seasonal changes in
      semen quality were associated with changes in the concentration of testosterone
      in plasma from yak bulls.

PMID- 19157730
TI  - Maternal age and parity influence ultrasonographic measurements of fetal growth
      in Dutch Warmblood mares.
AB  - Ultrasonographic examination of the equine fetus in mid-late gestation is usually
      performed only if there are concerns about fetal or maternal health. Even then it
      is difficult to determine whether development is 'normal' for gestational age
      because the reference values include considerable error margins. This study
      examined maternal factors that influence fetal growth with the aim of producing
      more precise late gestation fetal growth curves for Dutch Warmblood horses. Fetal
      development was monitored at 2-week intervals from day 100 of gestation until
      term in 32 mares ranging from 4 to 18 years in age; seven of the mares were
      primiparous. Transrectal and/or transabdominal ultrasonographic measurement of
      the fetal eye orbit, cranium, aorta, heart rate and of the combined thickness of
      uterus and placenta (CTUP) were performed using a portable ultrasound machine
      equipped with 6 MHz linear and 3.5 MHz curved array probes. During days 100-250
      of gestation, the CTUP was thicker in primiparous than multiparous mares
      (p<0.05). After day 220 the maximum cross-sectional area, but not diameter, of
      both the eye orbit and cranium were also greater in primiparous than multiparous
      mares (p<0.05). Fetal aorta diameter was not influenced by parity but was
      affected by maternal age, being smaller in mares > or =15 years of age than
      younger animals (p<0.05). Only biparietal cross-sectional surface area and aorta
      diameter increased linearly throughout late gestation. However, even allowing for
      the effects of parity and maternal age, the late gestational variation in fetal
      size is such that serial measurements may be required to definitively identify
      abnormal development.

PMID- 19157731
TI  - Effects of filtration through Sephadex columns improve overall quality parameters
      and "in vivo" fertility of subfertile refrigerated boar-semen.
AB  - This study was performed to test the effects of filtration through several
      chromatographic resins on the semen quality parameters (percentages of viability,
      altered acrosomes and morphological abnormalities, motion characteristics and the
      response to the Osmotic Resistance Test) of boar ejaculates of poor quality. Our
      results indicate that filtration through a non-ionic Sephadex resin bed (Sephadex
      G-15), combined with a glasswool subjection bed, induced an overall improvement
      of semen quality parameters, especially seen in a significant (P<0.05) decrease
      in the percentages of morphological abnormalities and an increase of several
      motility parameters related to velocity and linearity. Similar results, although
      less intense, were observed when the filtration through G-15 resin was
      accompanied by an ionically neutral polypropylene disk bed instead of glasswool.
      On the other hand, filtration through two separate ion-exchange Sephadex resins,
      cationic C-50 and anionic A-50, have less beneficial, and even detrimental,
      effects on boar-semen quality. In all cases, filtration was accompanied by a
      significant (P<0.01) decrease in the final concentration of the samples.
      Ultrastructural and lectin studies showed that the interaction between sperm and
      chromatographic resins depends on the resin type utilized, and in the case of G
      15 it seems that it works by trapping that sperm with not enough strength to
      overcome the physical resistance associated with chromatographic particles. When
      semen of poor quality was filtered through G-15 resin and then was utilized for
      "in vivo" fertility trials, a significant (P<0.05) increase in the percentage of
      fertility was observed, when compared with the same, but unfiltered, samples. In
      summary, our results strongly indicate that filtration through ionically inert,
      Sephadex chromatographic resins could be a very useful and practical method to
      improve both boar-semen quality and fertilizing ability, especially from mediocre
      and/or subfertile samples.

PMID- 19157732
TI  - Menopause-specific questionnaire assessment in US population-based study shows
      negative impact on health-related quality of life.
AB  - OBJECTIVE: To use the Menopause-Specific Quality of Life Questionnaire (MENQOL)
      to assess the impact of menopausal symptoms on health-related quality of life in
      a large US population-based study. METHODS: Participants were recruited from the
      US population through random-digit-dialing and probability sampling. Analyses
      included 2703 postmenopausal women 40-65 years old in our Menopause Epidemiology
      Study. Respondents answered a 30-min questionnaire, including the MENQOL.
      RESULTS: Scores for each domain were: vasomotor: 3.2+/-2.2; psycho-social: 3.3+/
      1.8; physical: 3.5+/-1.5; sexual: 2.9+/-2.1. There were significant differences
      in the MENQOL scores by age, smoking, exercise, education, employment status and
      BMI. Women aged 60-65 years (p<0.0001), with a bachelor's degree or higher level
      of education (p<0.0001), who exercised at least 3 days a week (p<0.0001), who had
      never smoked (p<0.0001), with a body mass index < or =25kg/m(2) (p<0.0001), and
      who had significantly lower scores indicating better quality of life. Hot flashes
      affected work (46.0%), social activities (44.4%), leisure activities (47.6%),
      sleep (82.0%), mood (68.6%), concentration (69.0%), sexual activity (40.9%),
      total energy level (63.3%) and overall quality of life (69.3%). CONCLUSION:
      Symptoms experienced during menopause and socio-demographic characteristics
      affect the quality of life in postmenopausal women. Hot flashes impact the daily
      activities of most postmenopausal women, especially those with more
      frequent/severe symptoms. Treatments that safely and effectively treat these
      symptoms could improve quality of life among postmenopausal women.

PMID- 19157733
TI  - Progestogens and target tissues: vascular systems.
AB  - Progestogens were mostly used in hormone replacement therapy (HRT) in the
      postmenopause. Therefore, our knowledge about cardiovascular effects mainly
      originates from studies using HRT, whereby the progestogen effects were assessed
      according to clinical endpoints, metabolic effects and influence on vascular
      markers in vitro or in vivo, respectively. Furthermore, the progestogens can be
      characterised in terms of their partial receptor properties by specific
      experimental models. These properties can positively or negatively influence the
      vascular system. Concerning the direct vascular effects, currently research is
      focussing on biochemical vascular active markers. Although evidence strongly
      supports that some of these markers can be used as predictors of certain
      cardiovascular events, it remains to be established that modifying circulating
      levels of these markers will influence the outcomes. These experiments, however,
      strongly indicate that for the progestogens no class-effects can be postulated.
      In HRT progestogens are primarily used to get endometrial safety, which should be
      fulfilled by all progestogens. Since in terms of the vascular system it is
      difficult to predict the net-overall effect due to the different complex partial
      effects, we preferentially recommend progestogens derived from progesterone which
      are rather neutral in terms of the vascular system for risk patients but
      effective in the endometrium, i.e. maintaining atrophic endometrium during long
      term continuous combined HRT. For women with hypertension especially HRT regimens
      can be recommended, which have been shown to stabilize or even lower blood
      pressure during well designed studies like with 24h-ambulatory blood pressure
      assessments. Further research is necessary to investigate the possibility of a
      more differential usage of the various progestogens regarding their effects on
      vascular systems.

PMID- 19157734
TI  - Influence of menopause on biochemical markers of endothelial dysfunction-A case
      control pilot study in North Indian population.
AB  - OBJECTIVE: Menopause, an estrogen deficient state, is known to increase the
      cardiovascular risk. Lipid changes accompanying menopause account for only few
      cases of coronary artery disease (CAD). Endothelium-dependent nitric oxide
      mediated vasodilatory mechanisms are also known to play a role in development of
      coronary artery disease, but studies in menopausal women are very few. This study
      was hence undertaken to see if nitric oxide (NO)-cyclic guanidine monophosphate
      (c-GMP) pathway is influenced by menopause. DESIGN: This study was a hospital
      based case-control study involving 100 women in age group 40-55 years. Of these,
      50 women were postmenopausal and 50 were premenopausal. Women with known risk
      factors for CAD were excluded. Fasting blood samples from these women were
      collected and analyzed for estradiol levels, lipid profile, apolipoprotein B,
      plasma nitric oxide, c-GMP and platelet nitric oxide using standard kits and
      reagents. Statistical analysis was done on SPSS and two-tailed p-value <0.05 was
      considered significant. RESULT: Postmenopausal women had significantly lower
      estradiol, plasma NO, and c-GMP levels as compared to premenopausal women
      (p<0.05). Cholesterol, low-density lipoprotein (LDL) cholesterol and
      apolipoprotein B (apo-B) levels were higher and HDL levels were lower in
      postmenopausal as compared to premenopausal women (p<0.05). Plasma NO showed a
      significant positive correlation with estradiol, HDL levels and negative
      correlation with apo-B levels. CONCLUSION: Menopause tends to downregulate NO-c
      GMP pathway resulting in endothelial dysfunction. The mechanism may be directly
      through estrogen receptors or indirectly through potentiation of dyslipidemia.

PMID- 19157735
TI  - Oxethazaine as the source of mephentermine and phentermine in athlete's urine.
AB  - The urine specimens of numerous athletes were found to be positive for
      mephentermine both in-competition and out-of-competition in Taiwan. The donor of
      one specimen claimed she had only taken Mucaine (contains oxethazaine) for
      relieving symptomatic peptic ulcer and gastritis. Oxethazaine is not included in
      the prohibited list of the World Anti-Doping Agency; however, its metabolized
      compounds, mephentermine and phentermine, are included in that list. This study
      applied LC-MS-MS to analyze the excretions of three volunteers who ingested
      oxethazaine and presented positive results for mephentermine and/or phentermine.
      Thus, oxethazaine is the source of mephentermine and phentermine. Moreover, the
      results showed that 48 brands of gastric medicines containing oxethazaine were
      legally imported or locally manufactured in Taiwan, information which could be
      useful for limiting the misuse of oxethazaine by athletes. The data suggested
      that the sports associations should warn athletes about the risks of taking
      oxethazaine.

PMID- 19157736
TI  - Development and standardization of a microalgae test for determining deaths by
      drowning.
AB  - The diatom test for the diagnosis of drowning is widely used in countries of the
      Northern Hemisphere such as France and Japan. In Latin America, however, it has
      not been adopted as a routine procedure in forensic autopsies. In aquatic
      ecosystems, dinoflagellates and some chlorophytes are microalgae that, like
      diatoms, have cell walls and other resistant structures. As a result, they can be
      found in tissues from drowning victims, which is important because diatoms may be
      rare under particular environmental conditions. On this basis, we propose to
      extend the "diatom test" to include other microalgae for the determination of
      death by drowning. In this work, we developed a standardized procedure for
      detecting microalgae in tissues from drowning victims, with techniques described
      in the international literature and designed by us. The corpses were recovered
      from coastal areas in Antofagasta Region, Chile, during summer 2005. The most
      effective procedure for the treatment of water and tissue samples involved the
      combination of enzymatic digestion (proteinase K) and chemical digestion. The
      technique allowed the recovery of dinoflagellate evidence belonging to genera
      Prorocentrum, Ceratium, Dinophysis and Protoperidinium; silicoflagellates of the
      genus Dictyocha; an undetermined, filamentous chlorophyte; entire valves of
      centric diatoms and fragments of pennate and centric diatoms. This is the first
      protocol using microalgae other than diatoms for forensic cases in Latin America,
      and particularly in Chile.

PMID- 19157737
TI  - [Budd-Chiari syndrome in sarcoidosis].

PMID- 19157738
TI  - Rectal villous tumours: MR features and correlation with TRUS in the preoperative
      evaluation.
AB  - AIM: The aim of this study was to assess the clinical relevance of MR and
      transrectal ultrasonography (TRUS) imaging of rectal villous tumours to elucidate
      the correlation between imaging results and specific histopathological tumour
      features, such as tumour size (T) and lymph node involvement (N), in order to
      establish the better technique for the pre-surgical patient evaluation. PATIENTS
      AND METHODS: 23 cases of villous tumours of the rectum were studied with phased
      array MR and TRUS. All patients underwent either surgical or endoscopic
      treatment. Final diagnosis was based on histopathological results. In particular,
      the following features were characterized by the imaging techniques mentioned
      above: lesion site, distance between lesion and ano-rectal junction, size,
      morphology and contrast enhancement of lesions, fluid layer around the lesion,
      alterations of the deep layers of the rectal wall, sphincter infiltration,
      presence or absence of mesorectal, iliac and obturatory lymphnode involvement.
      RESULTS: Histology established muscular involvement in 7 cases (T2), perirectal
      fat infiltration in 1 case (T3); in the remaining 15 cases, staging was Tis-T1.
      In 17/23 cases (73.9%) the lesions were correctly staged with both imaging
      techniques, whereas in 5/23 cases (21.7%) the lesions were overstaged. No cases
      were understaged. TRUS concorded with histological exams in 17/23 cases (73.9%).
      5/23 cases (21.7%) were overstaged and 1/23 (4%) was understaged. MR and TRUS
      were in accordance in 20/23 cases (86.9%). DISCUSSION: Considering the frequent
      degeneration of villous tumours, correct preoperative identification and precise
      evaluation of these lesions, such as the detection of rectal wall invasion, is
      essential in deciding optimal treatment strategy. MRI and TRUS allow the
      identification of specific features of villous tumours and of malignant
      degeneration, allowing for a correct local disease staging.

PMID- 19157739
TI  - Quantitative contrast enhanced ultrasound of the liver for time intensity curves
      Reliability and potential sources of errors.
AB  - INTRODUCTION: Time intensity curves for real-time contrast enhanced low MI
      ultrasound is a promising technique since it adds objective data to the more
      subjective conventional contrast enhanced technique. Current developments showed
      that the amount of uptake in modern targeted therapy strategies correlates with
      therapy response. Nevertheless no basic research has been done concerning the
      reliability and validity of the method. PATIENTS AND METHODS: Videos sequences of
      31 consecutive patients for at least 60s were recorded. Parameters analysed: area
      under the curve, maximum intensity, mean transit time, perfusion index, time to
      peak, rise time. The influence of depth, lateral shift as well as size and shape
      of the region of interest was analysed. RESULTS: The parameters time to peak and
      rise time showed a good stability in different depths. Overall there was a
      variation >50% for all other parameters. Mean transit time, time to peak and rise
      time were stable from 3 to 10cm depths, whereas all other parameters showed only
      satisfying results at 4-6cm. Time to peak and rise time were stable as well
      against lateral shifting whereas all other parameters had again variations over
      50%. Size and shape of the region of interest did not influence the results.
      DISCUSSION: (1) It is important to compare regions of interest, e.g. in a tumour
      vs. representative parenchyma in the same depths. (2) Time intensity curves
      should not be analysed in a depth of less than 4cm. (3) The parameters area under
      the curve, perfusion index and maximum intensity should not be analysed in a
      depth more than 6cm. (4) Size and shape of a region of interest in liver
      parenchyma do not affect time intensity curves.

PMID- 19157740
TI  - T2 mapping and dGEMRIC after autologous chondrocyte implantation with a fibrin
      based scaffold in the knee: preliminary results.
AB  - OBJECTIVE: To assess repair tissue (RT) after the implantation of BioCartII, an
      autologous chondrocyte implantation (ACI) technique with a fibrin-hyaluronan
      polymer as scaffold. T2 mapping and delayed Gadolinium Enhanced Magnetic
      Resonance Imaging of Cartilage (dGEMRIC) were used to gain first data on the
      biochemical properties of BioCartII RT in vivo. METHODS: T2 mapping and dGEMRIC
      were performed at 3T in five patients (six knee joints) who had undergone ACI 15
      27 months before. T2 maps were obtained using a pixel wise, mono-exponential non
      negative least squares fit analysis. For quantitative T1 mapping a dual flip
      angle 3D GRE sequence was used and T1 maps were calculated pre- and post-contrast
      using IDL software. Subsequent region of interest analysis was carried out in
      comparison with morphologic MRI. RESULTS: A spatial variation of T2 values in
      both hyaline, normal cartilage (NC) and RT was found. Mean RT T2 values and mean
      NC T2 values did not differ significantly. Relative T2 values were calculated
      from global RT and NC T2 and showed a small range (0.84-1.07). The relative delta
      relaxation rates (rDeltaR1) obtained from the T1 maps had a wider range (0.77
      4.91). CONCLUSION: T2 mapping and dGEMRIC provided complementary information on
      the biochemical properties of the repair tissue. BioCartII apparently can provide
      RT similar to hyaline articular cartilage and may become a less-invasive
      alternative to ACI with a periosteal flap.

PMID- 19157741
TI  - Description of Dietzia lutea sp. nov., isolated from a desert soil in Egypt.
AB  - An actinobacterial strain YIM 80766T was isolated from a soil sample collected
      from the eastern desert of Egypt, and its taxonomic position was investigated by
      a polyphasic approach. The organism was found to have a range of chemical and
      morphological properties consistent with its classification in the genus Dietzia.
      Phylogenetic analysis indicated that the levels of 16S rRNA gene sequence
      similarity between strain YIM 80766T and the other type strains of recognized
      members of the genus Dietzia were 97.0-98.9%. However, DNA-DNA hybridization
      values and phenotypic characteristics revealed that the strain differed from the
      currently recognized species of the genus Dietzia. Therefore, strain YIM 80766T
      represents a novel species of the genus Dietzia, for which the name Dietzia lutea
      sp. nov. is proposed. The type strain is YIM 80766T ( = KCTC 19232T = DSM 45074T
      = CCTCC AA 207008T). The 16S rRNA gene sequence of strain YIM 80766T has been
      deposited in GenBank under the accession number EU821598.

PMID- 19157742
TI  - Pseudomonas cichorii as the causal agent of midrib rot, an emerging disease of
      greenhouse-grown butterhead lettuce in Flanders.
AB  - Bacterial midrib rot of greenhouse-grown butterhead lettuce (Lactuca sativa L.
      var. capitata) is an emerging disease in Flanders (Belgium) and fluorescent
      pseudomonads are suspected to play an important role in the disease. Isolations
      from infected lettuces, collected from 14 commercial greenhouses in Flanders,
      yielded 149 isolates that were characterized polyphasically, which included
      morphological characteristics, pigmentation, pathogenicity tests by both
      injection and spraying of lettuce, LOPAT characteristics, FAME analysis, BOX-PCR
      fingerprinting, 16S rRNA and rpoB gene sequencing, as well as DNA-DNA
      hybridization. Ninety-eight isolates (66%) exhibited a fluorescent pigmentation
      and were associated with the genus Pseudomonas. Fifty-five of them induced an HR+
      (hypersensitive reaction in tobacco leaves) response. The other 43 fluorescent
      isolates were most probably saprophytic bacteria and about half of them were able
      to cause rot on potato tuber slices. BOX-PCR genomic fingerprinting was used to
      assess the genetic diversity of the Pseudomonas midrib rot isolates. The
      delineated BOX-PCR patterns matched quite well with Pseudomonas morphotypes
      defined on the basis of colony appearance and variation in fluorescent
      pigmentation. 16S rRNA and rpoB gene sequence analyses allowed most of the
      fluorescent isolates to be allocated to Pseudomonas, and they belonged to either
      the Pseudomonas fluorescens group, Pseudomonas putida group, or the Pseudomonas
      cichorii/syringae group. In particular, the isolates allocated to this latter
      group constituted the vast majority of HR+ isolates and were identified as P.
      cichorii by DNA-DNA hybridization. They were demonstrated by spray-inoculation
      tests on greenhouse-grown lettuce to induce the midrib rot disease and could be
      re-isolated from lesions of inoculated plants. Four HR+ non-fluorescent isolates
      associated with one sample that showed an atypical midrib rot were identified as
      Dickeya sp.

PMID- 19157743
TI  - Distribution and diversity of autotrophic bacteria in groundwater systems based
      on the analysis of RubisCO genotypes.
AB  - A molecular approach, based on the detection of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RubisCO) large subunit genes, was applied to investigate
      the distribution and diversity of autotrophic bacteria in groundwater systems.
      DNA extracts from 48 sampling stations, including a variety of pristine and
      polluted, shallow and deep-subsurface groundwater samples obtained from Germany
      and Austria, served as a template for the PCR amplification of form I (cbbL) and
      form II (cbbM) large subunit RubisCO genes. The majority of the samples (>80%)
      contained two different forms of RubisCO. In 17 samples, all three forms of
      RubisCO were identified. PCR products from four selected groundwater habitats
      containing all three forms of RubisCO were used to construct clone libraries.
      Based on restriction fragment length polymorphism (RFLP) analysis, 109 RubisCO
      clone-inserts were subjected to sequencing and phylogenetic analysis. With the
      exception of a form IA RubisCO sequence cluster obtained from deep subsurface
      samples, which was identical to the RubisCO genes described for Ralstonia
      metallidurans CH34, most sequences were distantly related to a variety of RubisCO
      species in chemolithoautotrophic Proteobacteria. Several sequences occurred in
      isolated lineages. These findings suggest that autotrophic bacteria with the
      capability to assimilate CO2 via the Calvin Cycle pathway are widespread
      inhabitants of groundwater systems.

PMID- 19157744
TI  - Sample preparation development and matrix effects evaluation for multianalyte
      determination in urine.
AB  - The development of a generic analytical method remains difficult when a high
      number of compounds has to be simultaneously considered. This study proposes an
      innovative strategy for the development of a solid phase extraction (SPE)
      procedure before liquid chromatography-mass spectrometry analysis of 34 diuretics
      and beta-blockers in urine samples. These compounds have been selected since they
      are often encountered in anti-doping control. The principle is based on the
      selection of representative analytes during SPE protocol optimization, allowing a
      drastic reduction of generated data and development time. To select the
      representative compounds, all substances were classified based on their SPE
      behavior with a generic method and groups were formed with the help of a
      chemometric tool, namely hierarchical cluster analysis (HCA). One representative
      analyte per group was selected and used for subsequent SPE method development.
      Once the SPE method was developed, compounds were analyzed by LC-MS and matrix
      effects were evaluated to determine the influence of the matrix on the SPE
      process and MS signal alteration due to endogenous compounds. As a result, matrix
      effects evaluation must be performed on all analytes; representative compounds
      previously selected for SPE development were unable to predict matrix effects.

PMID- 19157745
TI  - Characterization of the mangiferin-human serum albumin complex by spectroscopic
      and molecular modeling approaches.
AB  - The interactions between mangiferin and human serum albumin (HSA) were
      investigated by spectroscopy and molecular modeling. The results proved the
      formation of complex between mangiferin and HSA. Hydrophobic interaction
      dominated in the association reaction. Mangiferin statically quenched the
      fluorescence of HSA in a concentration dependent manner positively deviating from
      the linear Scatchard equation. The binding of mangiferin to HSA lead to changes
      in the conformation of HSA according to synchronous fluorescence spectra, FT-IR,
      UV-vis and CD data. The presence of amino acids and metal ion affected the
      binding constant of mangiferin-HSA complex. Computational mapping of the possible
      binding sites of mangiferin revealed the molecule to be bound in the large
      hydrophobic cavity of subdomain IIA.

PMID- 19157746
TI  - Quantitative analysis of colistin A and colistin B in plasma and culture medium
      using a simple precipitation step followed by LC/MS/MS.
AB  - An analytical method for quantitation of colistin A and colistin B in plasma and
      culture medium is described. After protein precipitation with acetonitrile (ACN)
      containing 0.1% trifluoroacetic acid (TFA), the supernatants were diluted with
      0.03% TFA. The compounds were separated on an Ultrasphere C18 column, 4.6 mm x
      250 mm, 5 microm particle size with a mobile phase consisting of 25% ACN in 0.03%
      TFA and detected with tandem mass spectrometry. The instrument was operating in
      ESI negative ion mode and the precursor-product ion pairs were m/z 1167.7-
      >1079.6 for colistin A and m/z 1153.7-->1065.6 for colistin B. The lower limit of
      quantification (LLOQ) for 100 microL plasma was 19.4 and 10.5 ng/mL for colistin
      A and B, respectively, with CV <6.2% and accuracy <+/-12.6%. For culture medium
      (50 microL+50 microL plasma), LLOQ was 24.2 and 13.2 ng/mL for colistin A and B,
      respectively, with CV <11.4% and accuracy <+/-8.1%. The quick sample work-up
      method allows for determination of colistin A and B in clinical samples without
      causing hydrolysis of the prodrug colistin methanesulfonate (CMS).

PMID- 19157747
TI  - Maisonneuve fracture.

PMID- 19157749
TI  - Hepatic portal venous gas after shock episode.

PMID- 19157748
TI  - Hemobilia as a late complication after blunt abdominal trauma: a case report and
      review of the literature.
AB  - BACKGROUND: Bleeding within the biliary tree, called hemobilia, is a rare
      complication after blunt hepatic trauma. OBJECTIVES: To report on a patient who
      developed hemobilia 1 month after a blunt abdominal injury and to discuss the
      diagnosis and treatment of hemobilia. CASE REPORT: A 17-year-old boy presented
      with upper gastrointestinal bleeding caused by hemobilia 1 month after a blunt
      liver injury. Angiography revealed a pseudoaneurysm of the right hepatic artery,
      which was successfully treated with embolization. CONCLUSIONS: The diagnosis of
      hemobilia first requires consideration of the diagnosis, particularly in patients
      with previous abdominal trauma. Hemobilia should be included in the differential
      diagnosis of upper gastrointestinal bleeding. Investigations of choice include
      computed tomography scan followed by angiography. During angiography, treatment
      can be done by endovascular embolization.

PMID- 19157750
TI  - TRIAD II: do living wills have an impact on pre-hospital lifesaving care?
AB  - BACKGROUND: Living wills accompany patients who present for emergent care. To the
      best of our knowledge, no studies assess pre-hospital provider interpretations of
      these instructions. OBJECTIVES: Determine how a living will is interpreted and
      assess how interpretation impacts lifesaving care. DESIGN SETTING: Three-part
      survey administered at a regional emergency medical system educational symposium
      to 150 emergency medical technicians (EMTs) and paramedics. Part I assessed
      understanding of the living will and do-not-resuscitate (DNR) orders. Part II
      assessed the living will's impact in clinical situations of patients requiring
      lifesaving interventions. Part III was similar to part II except a code status
      designation (full code) was incorporated into the living will. RESULTS: There
      were 127 surveys completed, yielding an 87% response rate. The majority were male
      (55%) and EMTs (74%). The average age was 44 years and the average duration of
      employment was 15 years. Ninety percent (95% confidence interval [CI] 84.6-95.4%)
      of respondents determined that, after review of the living will, the patient's
      code status was DNR, and 92% (95% CI 86.5-96.6%) defined their understanding of
      DNR as comfort care/end-of-life care. When the living will was applied to
      clinical situations, it resulted in a higher proportion of patients being
      classified as DNR as opposed to full code (Case A 78% [95% CI 71.2-85.6%] vs. 22%
      [95% CI 14.4-28.8%], respectively; Case B 67% [95% CI 58.4-74.9%] vs. 33% [95% CI
      25.1-1.6%], respectively; Case C 63% [95% CI 55.1-71.9%] vs. 37% [95% CI 28.1
      44.9%]), respectively. With the scenarios presented, this DNR classification
      resulted in a lack of or a delay in lifesaving interventions. Incorporating a
      code status into the living will produced statistically significant increases in
      the provision of lifesaving care. In Case A, intubation increased from 15% to 56%
      (p < 0.0001); Case B, defibrillation increased from 40% to 59% (p < 0.0001); and
      Case C, defibrillation increased from 36% to 65% (p < 0.0001). CONCLUSIONS:
      Significant confusion and concern for patient safety exists in the pre-hospital
      setting due to the understanding and implementation of living wills and DNR
      orders. This confusion can be corrected by implementing clearly defined code
      status into the living will.

PMID- 19157751
TI  - Of crashes, catheters, and confusion, 1984.

PMID- 19157752
TI  - Persistent left superior vena cava diagnosed by bedside echocardiography.
AB  - BACKGROUND: Persistent left superior vena cava (PLSVC) is a congenital anomaly
      with an estimated incidence of 0.3-0.5% in the normal population. Its usual
      discovery is often made by an abnormally positioned catheter inserted in the left
      subclavian or left jugular vein. In this situation, an easy bedside approach to
      confirm an anatomic variation in the central venous system is helpful. In the
      majority of cases, the PLSVC drains to the coronary sinus. OBJECTIVE: To describe
      the contribution of bedside echocardiography in diagnosing the unstable patient
      in whom there is suspicion of a PLSVC. CASE REPORT: A 29-year-old man underwent
      an emergent laparotomy for multiple intra-abdominal abscesses. Postoperatively,
      after insertion of a central line catheter through the left subclavian vein, a
      chest X-ray study showed the tip of the catheter in a left paramediastinal
      position instead of crossing the midline to the superior vena cava. A PLSVC was
      suspected. The patient was hemodynamically unstable; therefore, a bedside non
      invasive confirmation of the diagnosis of PLSVC was preferred. A transthoracic
      echocardiography study was performed after injection of agitated saline (creating
      air-filled microbubbles by shaking saline solution in a syringe), which showed
      that the coronary sinus was opacified, confirming the diagnosis of a PLSVC.
      CONCLUSION: In this brief report, we describe the contribution of
      echocardiography to the diagnosis of a PLSVC. Echocardiography is a reliable and
      easy diagnostic tool that allows a bedside approach in a patient in whom there is
      suspicion of a PLSVC, without administration of radiographic contrast.

PMID- 19157753
TI  - Uterine leiomyomata-related thromboembolic disease: a case report.
AB  - BACKGROUND: Venous thromboembolic disease rarely presents as a complication of
      uterine leiomyomata via inferior vena cava compression. CASE REPORT: We describe
      a case associated with venous thrombotic disease and subsequent pulmonary emboli
      and discuss the complexities of Emergency Department (ED) management. CONCLUSION:
      This case typifies the challenge of caring for the ill patient with multiple,
      potentially related disease processes whose treatments may actually conflict with
      one another.

PMID- 19157754
TI  - A patient presenting with dyspnea and abdominal pain after blunt trauma.

PMID- 19157755
TI  - Concussive symptoms in emergency department patients diagnosed with minor head
      injury.
AB  - BACKGROUND: Evidence-based protocols exist for Emergency Department (ED) patients
      diagnosed with minor head injury. These protocols focus on the need for acute
      intervention or in-hospital management. The frequency and nature of concussive
      symptoms experienced by patients discharged from the ED are not well understood.
      OBJECTIVES: To examine the prevalence and nature of concussive symptoms, up to 1
      month post-presentation, among ED patients diagnosed with minor head injury.
      METHODS: Eligible and consenting patients presenting to Kingston EDs with minor
      head injury (n = 94) were recruited for study. The Rivermead Post-Concussion
      Symptoms Questionnaire was administered at baseline and at 1 month post-injury to
      assess concussive symptoms. This analysis focused upon acute and ongoing
      symptoms. RESULTS: Proportions of patients reporting concussive symptoms were
      68/94 (72%) at baseline and 59/94 (63%) at follow-up. Seventeen percent of
      patients (18/102) were investigated with computed tomography scanning during
      their ED encounter. The prevalence of somatic symptoms declined between baseline
      and follow-up, whereas some cognitive and emotional symptoms persisted.
      CONCLUSION: The majority of patients who present to the ED with minor head
      injuries suffer from concussive symptoms that do not resolve quickly. This
      information should be incorporated into discharge planning for these patients.

PMID- 19157756
TI  - Prostatic abscess.

PMID- 19157757
TI  - Emergency department patients who stay more than 6 hours contribute to crowding.
AB  - BACKGROUND: Admitted and discharged patients with prolonged emergency department
      (ED) stays may contribute to crowding by utilizing beds and staff time that would
      otherwise be used for new patients. OBJECTIVES: To describe patients who stay > 6
      h in the ED and determine their association with measures of crowding. METHODS:
      This was a retrospective, observational study carried out over 1 year at a
      single, urban, academic ED. RESULTS: Of the 96,562 patients seen, 16,017 (17%)
      stayed > 6 h (51% admitted). When there was at least one patient staying > 6 h,
      60% of the time there was at least one additional patient in the waiting room who
      could not be placed in an ED bed because none was open. The walk-out rate was
      0.34 patients/hour when there were no patients staying in the ED > 6 h, vs. 0.77
      patients/hour walking out when there were patients staying > 6 h in the ED (p <
      0.001). When the ED contained more than 3 patients staying > 6 h, a trend was
      noted between increasing numbers of patients staying in the ED > 6 h and the
      percentage of time the ED was on ambulance diversion (p = 0.011). CONCLUSION: In
      our ED, having both admitted and discharged patients staying > 6 h is associated
      with crowding.

PMID- 19157758
TI  - Still crashing after all these years.

PMID- 19157759
TI  - Health care provider attitudes and practices regarding adolescent immunizations:
      a qualitative study.
AB  - OBJECTIVE: Assess health care providers' attitudes and practices regarding
      adolescent immunizations, including factors that either impede or facilitate
      vaccination. METHODS: Focus groups-In 2005, 3 focus groups were conducted in
      Monroe County, NY for (1) urban primary care physicians (PCPs); (2) suburban
      PCPs; and (3) nurses from practices represented in PCP groups. Audiotaped
      discussions were transcribed and analyzed using Atlas.ti. Key informant
      interviews-We recruited knowledgeable informants (18 physicians, 6 nurses) from
      across the US. The authors conducted in-depth telephone interviews with the
      participants, typed their interview notes, and sent them to the participant for
      verification. Separately for nurses, urban physicians, and suburban physicians
      results for each question were listed and reviewed by the authors. Themes were
      added to those from the focus groups. RESULTS: Three overarching themes were
      identified: professional buy-in (e.g., reimbursement, professional organization
      recommendations, disease and vaccine characteristics, office consensus);
      parent/adolescent buy-in (e.g., school requirements, perception of MD
      recommendations, cost and insurance coverage, media reports, disease and vaccine
      characteristics, "vaccine fatigue"), and delivery factors (e.g., vaccine supply,
      ordering, timing and scheduling, consent). CONCLUSIONS: Providers identified
      intertwined system issues that color their attitudes about adolescent
      immunization. PRACTICE IMPLICATIONS: Buy-in and delivery factors must be
      addressed before high immunization rates will be achieved.

PMID- 19157760
TI  - Impact of two types of Internet-based information on medical students'
      performance in an Objective Structured Clinical Exam (OSCE).
AB  - OBJECTIVES: Internet-based information has potential to impact physician-patient
      relationships. This study examined medical students' interpretation and response
      to such information presented during an objective clinical examination. METHOD:
      Ninety-three medical students who had received training for a patient centered
      response to inquiries about alternative treatments completed a comprehensive
      examination in their third year. In 1 of 12 objective structured clinical exams,
      a SP presented Internet-based information on l-theanine - an amino acid available
      as a supplement. In Condition A, materials were from commercial websites; in
      Condition B, materials were from the PubMed website. RESULTS: Analyses revealed
      no significant differences between Conditions in student performance or patient
      (SP) satisfaction. Students in Condition A rated the information less compelling
      than students in Condition B (z=-1.78, p=.037), and attributed less of the
      treatment's action to real vs. placebo effects (z=-1.61, p=.053). CONCLUSIONS:
      Students trained in a patient centered response to inquiries about alternative
      treatment perceived the credibility of the two types of Internet-based
      information differently but were able to respond to the patient without
      jeopardizing patient satisfaction. Approach to information was superficial.
      Training in information evaluation may be warranted.

PMID- 19157762
TI  - Patient-provider communication: understanding diabetes management among adult
      females.
AB  - OBJECTIVE: The purpose of this study was to explore how adult women manage their
      diabetes. Recommendations for improving adherence and opportunities to maximize
      communication between the healthcare provider and individuals who have type 2
      diabetes also were described. METHODS: An exploratory qualitative descriptive
      design was used to describe the experience of living with type 2 diabetes in
      adult females. Data were obtained via individual in-depth interviews with five
      women over age 50 with type 2 diabetes. Participants were interviewed
      individually and participated in a focus group. RESULTS: Participants clearly
      identified three major themes affecting adherence to treatment regimens:
      communication with the healthcare provider, knowledge of diabetes, and the
      consequences of poor glycemic control. For these participants, patient-provider
      communication was the most important factor affecting diabetes adherence.
      CONCLUSION: Individual autonomy asserted in day-to-day management is often
      perceived as non-compliance by the healthcare provider; while provider's
      descriptions of potential severe complications are viewed as scare tactics by the
      patients. PRACTICE IMPLICATIONS: Improved communication offers the clinician the
      opportunity to develop a partnership with patients to build mutually acceptable
      treatment plans and reach mutually agreed upon goals. Empowering the individual
      with skills needed to negotiate treatment regimens will encourage positive health
      decisions and improved outcomes.

PMID- 19157761
TI  - Dependence and caring in clinical communication: the relevance of attachment and
      other theories.
AB  - OBJECTIVE: Clinical relationships are usually asymmetric, being defined by
      patients' dependence and practitioners' care. Our aims are to: (i) identify
      literature that can contribute to theory for researching and teaching clinical
      communication from this perspective; (ii) highlight where theoretical development
      is needed; and (iii) test the utility of the emerging theory by identifying
      whether it leads to implications for educational practice. METHODS: Selective and
      critical review of research concerned with dependence and caring in clinical and
      non-clinical relationships. RESULTS: Attachment theory helps to understand
      patients' need to seek safety in relationships with expert and authoritative
      practitioners but is of limited help in understanding practitioners' caring.
      Different theories that formulate practitioners' care as altruistic, rewarded by
      personal connection or as a contract indicate the potential importance of
      practitioners' emotions, values and sense of role in understanding their clinical
      communication. CONCLUSION: Extending the theoretical grounding of clinical
      communication can accommodate patients' dependence and practitioners' caring
      without return to medical paternalism. PRACTICE IMPLICATIONS: A broader
      theoretical base will help educators to address the inherent subjectivity of
      clinical relationships, and researchers to distinguish scientific questions about
      how patients and clinicians are from normative questions about how they should
      be.

PMID- 19157763
TI  - Implementing patient decision support tools: moving beyond academia?
AB  - OBJECTIVE: To ascertain the feasibility of implementing three decision support
      tools (DSTs) for people with rectal cancer within the surgical consultation.
      METHODS: Twenty colorectal surgeons participated in a focus group or individual
      interviews. Colorectal surgeons were also asked to complete a self-administered
      questionnaire. RESULTS: All surgeons responded encouragingly to the concept of
      DSTs. However, for every positive statement an accompanying caveat was made and
      these were either a criticism of each tool or a barrier to their implementation.
      Surgeons stated DSTs should be used by patients and surgeons together (80%). The
      majority (70-75%) thought each tool was 'useful' or 'extremely useful'. However,
      there were strong views that in their current form the DSTs would not feasible to
      be used within the surgical consultation. Time restraints, personal and clinical
      characteristics of the patient, the content of each tool, the potential negative
      impact on the doctor-patient relationship were noted as real barriers to their
      implementation. CONCLUSION: Surgeons have identified a number of barriers that
      may limit implementation of DSTs into routine clinical practice. PRACTICE
      IMPLICATIONS: Feasibility and implementation studies have the potential to
      provide important information to help guide development, evaluation and
      implementation of DSTs.

PMID- 19157764
TI  - Preventing obesity: challenges and pitfalls for health promotion.
AB  - OBJECTIVE: To explore challenges to health promotion strategies against obesity,
      with special attention to the Scandinavian context. METHODS: Analytic induction,
      a procedure for verifying theories and propositions, based on purposefully
      selected literature references, with subsequent critical reflection. RESULTS:
      Health promotion efforts against obesity face challenges related to the unequal
      distribution of vulnerability to weight gain within the population, and to the
      complex neuroregulatory determinants that explain why obesity is not just a
      simple matter of lifestyle. Cultural understandings of identity and morality may
      create victim blaming and disempowerment, thus obstructing clinical health
      promotion strategies for weight control. Finally, the conceptual validity of
      obesity measurements and their predictive power deserves attention. CONCLUSION:
      Preventing obesity is difficult. Awareness of individual vulnerability and
      neurobiological mechanisms that lead to weight gain must be taken into account
      when strategies for health promotion are developed. These strategies must
      transcend a simplistic energy balance view. PRACTICE IMPLICATIONS: Clinical
      health promotion needs to be highly individualized and tailored. Preventing
      weight gain requires attention to the person's sociodemographic, cultural and
      genetic characteristics. Cultural trends such as sedentary lifestyles and the
      nutrition transition should be counteracted without turning body weight control
      into a question of morality and inferior identity.

PMID- 19157765
TI  - Big gap between risk perception for breast cancer and risk factors: nationwide
      survey in Korea.
AB  - OBJECTIVE: To explore perceived risk of breast cancer among Korean women and to
      investigate factors associated with perceived risk of breast cancer. METHODS: A
      telephone survey using random digit dialing was conducted with an age- and region
      stratified random sample of women in Korea. The study population consisted of
      1000 women who participated in telephone surveys in which a 21-item questionnaire
      was administered. RESULTS: This study showed a significant level of comparative
      optimism in breast cancer risk perception in Korean women with an average risk of
      breast cancer. According to the multivariate analysis, younger age, family
      history of breast cancer, and history of benign breast disease were the factors
      associated with higher perceived comparative risk of breast cancer. CONCLUSION:
      The finding that a limited number of breast cancer risk factors were related to
      perceived risk of breast cancer is worrying because women with other risk factors
      for breast cancer may believe themselves to be at lower risk. PRACTICE
      IMPLICATIONS: It is necessary for women to understand their risk factor profiles
      to avoid biased optimism or pessimism.

PMID- 19157766
TI  - Somatotropin response in vitro to corticosterone and triiodothyronine during
      chick embryonic development: Involvement of type I and type II glucocorticoid
      receptors.
AB  - Corticosterone (CORT) can stimulate growth hormone (GH) secretion on embryonic
      day (e) 12 in the chicken. However, CORT failed to induce GH secretion on e20 in
      a single report, suggesting that regulation of GH production changes during
      embryonic development. Secretion in response to CORT during embryonic development
      is modulated by the thyroid hormones triiodothyronine (T(3)) and thyroxine
      (T(4)). Growth hormone responses on e12 involve both glucocorticoid (GR) and
      mineralocorticoid receptors (MR); however, involvement of MR has not been
      evaluated past e12. To further define changes in somatotroph responsiveness to
      CORT, pituitary cells obtained on e12-e20 were cultured with CORT alone and in
      combination with T(3) and GH-releasing hormone (GHRH). Growth hormone mRNA levels
      and protein secretion were quantified by quantitative real-time polymerase chain
      reaction (qRT-PCR) and radioimmunoassay (RIA), respectively. Corticosterone
      significantly increased GH mRNA and protein secretion on e12; however, mRNA
      concentration and protein secretion were unaffected on e20. Contributions of GR
      and MR in CORT responses were evaluated using GR and MR antagonists. Treatment
      with a GR-specific antagonist effectively blocked the CORT-induced increase in GH
      secretion on e12. The same treatment on e20 had no effect on GH secretion. These
      findings demonstrate that GR is directly involved in glucocorticoid stimulation
      of GH secretion at the time of somatotroph differentiation but is not regulatory
      at the end of embryonic development. We conclude that positive somatotroph
      responses to CORT are lost during chicken embryonic development and that GR is
      the primary regulator of CORT-induced GH secretion.

PMID- 19157767
TI  - Interleukin-1 receptor antagonist expression in the equine endometrium during the
      peri-implantation period.
AB  - To identify factors involved in the establishment of pregnancy in the mare,
      endometrium was collected from day 13 (day 0=day of ovulation) cyclic and day 13,
      19, and 25 pregnant animals. From initial cDNA subtraction studies, interleukin-1
      receptor antagonist (IL-1RN) mRNA was found as a candidate molecule expressed
      uniquely in the pregnant endometrium. Expression of IL-1RN mRNA was markedly
      increased in day 19 and 25 gravid endometrium. In situ hybridization analysis
      revealed that IL-1RN mRNA was localized to the glandular epithelium. Interleukin
      1 receptor antagonist (IL-1RN) protein was found in the extracts of day 25 gravid
      endometrium and was immunochemically localized to the glandular
      epithelium/luminal cavity of the pregnant uterus. High concentrations of
      estradiol-17beta (E(2)) were detected in day 25 conceptuses. Concentrations of
      E(2) were higher in the gravid endometrial portion than in other endometrial
      regions. On the other hand, progesterone concentrations did not differ among
      endometrial samples analyzed. Furthermore, the expression of IL-1RN mRNA was up
      regulated in endometrium culture samples treated with 10 ng/mL E(2) and 10 ng/mL
      progesterone. In the analysis of related gene expression, increased amounts of IL
      1alpha and IL-6 mRNA were also found in the day 25 gravid endometrium; however,
      these expressions in endometrial culture samples were not up-regulated by the
      steroid treatment. These results indicate that expression of IL-1RN in the
      endometrium is likely regulated by E(2) and progesterone and suggest that IL-1RN
      regulates the degree of IL-1 signal transduction and thereby plays an important
      role in the establishment of equine pregnancy.

PMID- 19157768
TI  - Peripheral arterial disease and methylenetetrahydrofolate reductase (MTHFR) C677T
      mutations: A case-control study and meta-analysis.
AB  - OBJECTIVE: Hyperhomocysteinaemia is associated with peripheral arterial disease
      (PAD). There are inter-individual variations in the metabolism of homocysteine
      because of genetic polymorphisms. This study analyzed the role of one
      polymorphism that is associated with raised homocysteine, as a risk factor for
      PAD. METHODS: This study considered the association of methylenetetrahydrofolate
      reductase (MTHFR) C677T polymorphisms with the incidence of PAD by performing a
      case-control study and a cross sectional study of homocysteine levels. We
      recruited 133 patients with PAD in Norfolk and compared the MTHFR allele
      distribution with 457 healthy individuals. We also carried out a meta-analysis to
      place our data within the context of other published studies. We searched
      Medline, Embase, and Cochrane databases up to March 2008 for any studies on the
      association between MTHFR C677T polymorphism and PAD. RESULTS: The MTHFR C677T
      allele frequencies in the cases and controls were 0.37 and 0.33, and the odds
      ratios for the association of the 677 T allele or TT genotype with PAD were 1.18
      (95% Confidence Interval [CI] 0.89, 1.58) and 1.99 (95% CI 1.09, 3.63).
      Homozygotes for the MTHFR C677T mutation had higher concentrations of plasma
      total homocysteine, odds ratio 2.82 (95% CI 1.03, 7.77) compared to homozygotes
      for the MTHFR 677 CC genotype. Twelve of 72 articles retrieved from the database
      search reported the prevalence of mutations in PAD patients. A meta-analysis of 9
      appropriate studies, including our own, showed that being homozygous for the
      C677T allele was associated with an increased risk of PAD, pooled odds ratio 1.36
      (95% CI 1.09, 1.68). CONCLUSION: We have found a strong association between
      raised homocysteine, the TT genotype, and PAD.

PMID- 19157769
TI  - Sentinel lymphadenectomy for the staging of clinical axillary node-negative
      breast cancer before neoadjuvant chemotherapy.
AB  - BACKGROUND: Several authors reported sentinel lymph node biopsy (SLNB) after
      neoadjuvant chemotherapy (NC). Nevertheless, the ideal time of SLNB is still a
      matter of debate. METHODS: We evaluated the feasibility and the accuracy of SLNB
      before NC using a combined procedure (blue dye and radio-labelled detection)
      before NC. Axillary lymph node dissection (ALND) was performed after completion
      of NC in a homogeneous cohort study with clinically axillary node-negative breast
      cancer. RESULTS: Among the 20 women who had metastatic SLNB (65%), 4 (20%) had
      additional metastatic node on ALND. By contrast, all the 11 women who had no
      metastatic SLNB had no involved nodes in the ALND. The SLN identification rate
      before NC was 100% with any false negative. CONCLUSIONS: SLNB before NC is a
      feasible and an accurate diagnostic tool to predict the pre-therapeutic axilla
      status. These findings suggest that ALND may be avoided in patients with a
      negative SLNB performed before NC.

PMID- 19157770
TI  - [Efficacy of a low dose of ketamine in reduction of propofol-injection-related
      pain].

PMID- 19157772
TI  - [Rhabdomyolysis in severe acute asthma].

PMID- 19157773
TI  - [Feasibility of out-of-hospital management of non-heart-beating donors in Seine
      Saint-Denis: one year retrospective study].
AB  - The use of non-heart-beating donors (NHBD) could help shorten the list of
      patients who are waiting for a kidney transplant. The aim of this study was to
      evaluate efficiency of prehospital management of non-heart-beating donors in
      Seine-Saint-Denis area. We performed a retrospective cohort study of non-heart
      beating donor managed by prehospital medical team of Samu 93 from February 2007
      to January 2008. There were 28 non-heart-beating donors included consecutively.
      Twenty-five NHBD (89%) were canuled by Gillot probe within 150 min from patient
      collapse. Fourteen NHBD were harvested and 17 kidneys were transplanted. Six
      month survival rate for NHBD grafts was 94%. In the same time, eight brain dead
      donors were managed by Samu 93 and were harvested leading to transplant 16
      kidneys. Finally, 50% of overall kidney transplant activity in Seine-Saint-Denis
      was provided by NHBD grafts.

PMID- 19157774
TI  - Gene expression, cytoskeletal changes and extracellular matrix synthesis in human
      osteoblasts treated with cyclosporin A.
AB  - Cyclosporin A (CyA) is an immunosuppressive agent used to prevent allograft
      rejection, but unfortunately it causes adverse effects such as bone diseases,
      osteoporosis and osteomalacia. These pathologies involve an imbalance between
      synthesis, degradation and mineralization of extracellular matrix. CyA can modify
      extracellular matrix components such as glycosaminoglycans (GAG) and collagen
      fibers. In addition, normal cell activity is dependent on cell morphology and
      substrate cell attachment. We treated normal human osteoblasts with CyA and
      analyzed: (i) gene expression by a microarray method; (ii) extracellular GAG and
      collagen after (3)H-glucosamine and Western blot analysis; and (iii) cytoskeletal
      changes, using actin and tubulin fluorescent antibodies. CyA increased intra- and
      extracellular GAG and extracellular GAG classes such as hyaluronic acid,
      chondroitin sulphate, and dermatan sulphate; there was no noteworthy effect on
      heparan sulphate and the ratio of non-sulphated to sulphated GAG. In osteoblast
      cultures the drug reduced cytoskeletal actin, while tubulin did not change. In
      vivo the osteoblasts showed morphological changes with different extracellular
      matrix synthesis. Microarray analysis indicated the inhibition of gene pathways
      related to Wnt signaling molecules, and the cytoskeletal and focal adhesion
      cascade. In in vitro human osteoblasts CyA modified gene expression related to
      cytoskeletal pattern organization and cell morphology. Since in bone pathologies
      osteoblasts show different morphology related to cell size, these data suggest
      that in vivo osteoblast different functions could be dependent on alteration of
      osteoblast differentiation.

PMID- 19157775
TI  - [Optimal virologic monitoring of hepatitis C in 2009: Treatment duration depends
      on the speed of virologic response and the duration of the negative reaction].

PMID- 19157777
TI  - Superresolution with compound Markov random fields via the variational EM
      algorithm.
AB  - This study deals with a reconstruction-type superresolution problem and the
      accompanying image registration problem simultaneously. We propose a Bayesian
      approach in which the prior is modeled as a compound Gaussian Markov random field
      (MRF) and marginalization is performed over unknown variables to avoid
      overfitting. Our algorithm not only avoids overfitting, but also preserves
      discontinuity in the estimated image, unlike existing single-layer Gaussian MRF
      models for Bayesian superresolution. Maximum-marginal-likelihood estimation of
      the registration parameters is carried out using a variational EM algorithm where
      hidden variables are marginalized out, and the posterior distribution is
      variationally approximated by a factorized trial distribution. High-resolution
      image estimates are obtained through the process of posterior computation in the
      EM algorithm. Experiments show that our Bayesian approach with the two-layer
      compound model exhibits better performance both in quantitative measures and
      visual quality than the single-layer model.

PMID- 19157776
TI  - Effect of quetiapine vs. placebo on response to two virtual public speaking
      exposures in individuals with social phobia.
AB  - OBJECTIVE: Clinical practice and open-label studies suggest that quetiapine (an
      atypical anti-psychotic) might improve symptoms for individuals with social
      anxiety disorder (SAD). The purpose of this study was to provide a rigorous test
      of the acute impact of a single dose of quetiapine (25mg) on SAD symptoms.
      METHOD: Individuals with SAD (N=20) were exposed to a 4-min virtual reality (VR)
      public speaking challenge after having received quetiapine or placebo (double
      blind) 1h earlier. A parallel VR challenge occurred 1 week later using a counter
      balanced cross-over (within subject) design for the medication-placebo order
      between the two sessions. RESULT: There was no significant drug effect for
      quetiapine on the primary outcome measures. However, quetiapine was associated
      with significantly elevated heart rate and sleepiness compared with placebo.
      CONCLUSION: Study findings suggest that a single dose of 25mg quetiapine is not
      effective in alleviating SAD symptoms in individuals with fears of public
      speaking.

PMID- 19157778
TI  - A case study of multiple-treatments meta-analysis demonstrates that covariates
      should be considered.
AB  - OBJECTIVE: To illustrate the potential and challenges of the simultaneous
      analysis of a network of trials, using as a case study the investigation of the
      relative effectiveness of four topical fluoride treatments and two control
      interventions (placebo and no treatment) in preventing dental caries in children.
      STUDY DESIGN AND SETTING: We performed multiple-treatments meta-analysis within a
      Bayesian framework by synthesizing six Cochrane reviews. We explored the
      compatibility between direct and indirect evidence and adjusted the results using
      a meta-regression model to take into account differences in the year of
      randomization across studies. RESULTS: The validity of our conclusions for the
      superiority of fluoride toothpaste as indicated from the initial network analysis
      using Bayesian methods was challenged when we adjusted for possible confounders.
      The network was dominated by studies comparing placebo with toothpaste, which
      were older and had been carried out in populations with higher baseline risk than
      studies involving other fluoride modalities. CONCLUSION: After adjusting for
      possible differences across studies, we did not find clear evidence that any
      topical fluoride modality is more effective than any other. Multiple-treatments
      meta-analysis methods allow for more detailed investigations than naive methods
      in the analysis of indirect evidence on treatment effects.

PMID- 19157779
TI  - Tongue color analysis and discrimination based on hyperspectral images.
AB  - Human tongue is one of the important organs of the body, which carries abound of
      information of the health status. Among the various information on tongue, color
      is the most important factor. Most existing methods carry out pixel-wise or RGB
      color space classification in a tongue image captured with color CCD cameras.
      However, these conversional methods impede the accurate analysis on the subjects
      of tongue surface because of the less information of this kind of images. To
      address problems in RGB images, a pushbroom hyperspectral tongue imager is
      developed and its spectral response calibration method is discussed. A new
      approach to analyze tongue color based on spectra with spectral angle mapper is
      presented. In addition, 200 hyperspectral tongue images from the tongue image
      database were selected on which the color recognition is performed with the new
      method. The results of experiment show that the proposed method has good
      performance in terms of the rates of correctness for color recognition of tongue
      coatings and substances. The overall rate of correctness for each color category
      was 85% of tongue substances and 88% of tongue coatings with the new method. In
      addition, this algorithm can trace out the color distribution on the tongue
      surface which is very helpful for tongue disease diagnosis. The spectrum of
      organism can be used to retrieve organism colors more accurately. This new color
      analysis approach is superior to the traditional method especially in achieving
      meaningful areas of substances and coatings of tongue.

PMID- 19157780
TI  - Management of severe hypophosphatemia.

PMID- 19157781
TI  - The 12th John M. Kinney Nestle Nutrition awards.

PMID- 19157782
TI  - Fixation of autogenous bone grafts with ethyl-cyanoacrylate glue or titanium
      screws in the calvaria of rabbits.
AB  - This study compared the fixation of autogenous onlay bone grafts with
      cyanoacrylate glue (Super Bonder) and with titanium screws. Twenty rabbits
      underwent bilateral parietal ostectomies. Bone segments were fixed anteriorly to
      the resulting bone defect. In group I, the grafts were fixed with 4 mm long, 1.5
      mm diameter screws; in group II, adhesive was used. The animals were killed after
      5, 15, 30, 60 and 120 days. Histomorphometric analysis was used to quantify the
      maintenance of the graft area. Discrete areas of inflammatory reaction were seen
      in both groups after 5 days and for group II after 15 days. After 30 days, new
      bone formation was seen at the interface of the grafts. After 120 days, the graft
      was incorporated into the host bed in group I and partially incorporated in group
      II. There was a significant statistical difference regarding the mean graft areas
      between 15 and 120 days (p<0.001) and between fixation methods (p<0.002).
      Fixation with adhesive promoted a significantly greater area of bone graft than
      screw fixation, independent of time period. The adhesive was biocompatible,
      presented similar stability to the screw and maintained the bone area, although
      there was a delay in graft incorporation.

PMID- 19157783
TI  - Retention of lipiodol after parotid gland sialography.
AB  - There is limited information about the retention of lipiodol in the parotid gland
      after parotid gland sialography. This study assesses the prevalence of lipiodol
      retention after parotid sialography and determines if retention of lipiodol is
      related to the sialography technique or the underlying salivary gland pathology.
      Using the electronic hospital database (1996-2006), 66 out of 565 patients were
      identified who had additional maxillofacial radiographic examinations after the
      initial sialography. Additional radiographs up to October 2007 were included;
      these were orthopantomographic radiographs in all cases. In 28 patients (42%)
      signs of lipiodol retention were observed (mean radiographic follow-up: 15+/-13
      months). Retention was characterized by small radiopaque spots in the periphery
      of the gland. Lipiodol retention was predominantly associated with a fausse route
      (n=8) or the presence of salivary gland disease (sialectasia; n=17). In 9
      patients with signs of lipiodol retention, a series of radiographs was available.
      Lipiodol radiodensities decreased in size during 28 months, and could disappear
      gradually (follow-up 14-57 months). Despite the high frequency of retention of
      small depots of lipiodol for years after sialography in patients subjected to
      additional radiographic examinations, no clinically adverse effects were
      observed.

PMID- 19157784
TI  - Postictal serum nucleotidases activities in patients with epilepsy.
AB  - Adenosine, a potent anticonvulsant, can be produced in the body by the hydrolysis
      of adenine nucleotides through the action of ecto- or soluble nucleotidases.
      Changes in nucleotide hydrolysis occur after pentylenetetrazol-induced epileptic
      events. We evaluated serum ATP, ADP and AMP hydrolysis rates and soluble
      nucleotide phosphodiesterase (PDEase) activity at 5, 10, 15, 30 and 60 min, and
      12h following an epileptic event. Fifteen patients (seven female, eight male;
      mean age 15.5 years) were included in the study. The type of seizure was
      generalized in four patients and was localization related in the remaining 11.
      There were no differences in adenine nucleotide hydrolysis rates between patients
      and healthy subjects in the interictal stage. In comparison with controls, ATP,
      ADP and AMP hydrolysis rates were significantly increased at 5 min (53+/-1.4%,
      79.2+/-2.8% and 37.0+/-2.6%, respectively) and up to 30 min following the
      epileptic event. In contrast to ADP and AMP, ATP hydrolysis remained
      significantly increased at 60 min (71.4+/-1.6%), returning to the basal level
      after 12h. Serum PDEase activity was also significantly higher in the patients
      than in healthy subjects, peaking at 15 min (61+/-2.9%) and remaining
      significantly increased up to 60 min (4.6+/-1.2%) following the epileptic
      episode. Globally, the variations in the postictal serum ADP hydrolysis rate
      almost overlapped those of AMP hydrolysis, whereas changes in the ATP hydrolysis
      rate overlapped those of PDEase activity. The clinical significance of this
      elevation in postictal soluble serum nucleotidase activity remains to be
      clarified. However, it is possible to hypothesize that the higher nucleotidase
      activity might play a role in the modulation of epileptic events.

PMID- 19157785
TI  - Insulin resistance and secretion in vivo: effects of different antipsychotics in
      an animal model.
AB  - Atypical antipsychotics now represent the mainstay of treatment for patients with
      schizophrenia. Unfortunately, as a class they have also been associated with an
      increased risk of weight gain and metabolic abnormalities, including type 2
      diabetes. We have investigated the diabetogenic effects of a spectrum of
      antipsychotics, both atypical and typical. Healthy animals were treated acutely
      with clozapine (10 mg/kg), olanzapine (3.0 mg/kg), risperidone (1 mg/kg),
      ziprasidone (3 mg/kg) or haloperidol (0.25 mg/kg) and tested using the
      hyperinsulinemic-euglycemic and hyperglycemic clamp procedures. Clozapine and
      olanzapine had a rapid and potent effect on insulin sensitivity by lowering the
      glucose infusion rate and increasing hepatic glucose production. Both clozapine
      and olanzapine, as well as risperidone, decreased peripheral glucose utilization.
      Neither ziprasidone nor haloperidol had a significant impact on insulin
      sensitivity. In the hyperglycemic clamp, clozapine and olanzapine impaired beta
      cell function as reflected by a decrease in insulin secretion. Results confirm
      that 1) antipsychotic medications have an immediate impact on metabolic
      parameters and 2) the various atypical antipsychotics differ in their propensity
      to acutely induce metabolic side effects. Our data also support the preclinical
      use of these clamp procedures in screening putative antipsychotics.

PMID- 19157786
TI  - Impaired regional hemodynamic response in schizophrenia during multiple
      prefrontal activation tasks: a two-channel near-infrared spectroscopy study.
AB  - In schizophrenia, dysfunction of the prefrontal cortex (PFC), regarded as a core
      feature of the disease, has been investigated by different neuroimaging methods.
      Near infrared spectroscopy (NIRS), a novel neurophysiological method, is being
      increasingly used in the investigation of frontal dysfunction in schizophrenia.
      However, NIRS measurements during multiple frontal activation tasks have been
      rarely reported. The purpose of this study was to compare hemodynamic changes in
      the PFC between patients with schizophrenia and healthy controls during four
      different types of frontal lobe tasks using a 2-channel NIRS system. Thirty
      patients with schizophrenia and thirty age- and gender-matched healthy controls
      were enrolled in this study. In both groups, changes in oxygenated hemoglobin
      concentration (Delta[oxyHb]) at the bilateral forehead were measured during
      Verbal fluency test letter version (VFT-letter), VFT category version, Tower of
      Hanoi (TOH), the Sternberg and Stroop tasks. Regarding Delta[oxyHb] in PFC, a
      diagnosis group effect was found for VFT-letter and TOH. Significant negative
      correlation was found between left Delta[oxyHb] during TOH and negative and
      cognitive symptom scores in schizophrenia patients. Right Delta[oxyHb] during TOH
      also showed significant negative correlation with cognitive symptoms scores. No
      significant correlation between Delta[oxyHb] and clinical characteristics were
      observed during VFT-letter. These findings suggest that among a battery of
      frontal lobe tasks administered to schizophrenia patients, VFT-letter and TOH are
      more sensitive to detect PFC activation, as indicated by Delta[oxyHb] using a 2
      channel NIRS. Taken together, these findings and those of previous neuroimaging
      studies suggest that VFT-letter and TOH might represent possible candidate
      physiological markers of prefrontal dysfunction in schizophrenia, though
      extensive testing in clinical settings will be necessary.

PMID- 19157787
TI  - Physical activity levels of persons with mental illness attending psychiatric
      rehabilitation programs.
AB  - This study objectively measured physical activity levels in overweight and obese
      adults with severe mental illness and examined relationships among psychiatric
      symptoms, cognitive functioning and physical activity. A diverse sample (50%
      female, 50% African American) of overweight and obese adults (n=55) with mental
      illness were asked to wear accelerometers for 4 days. Study participants averaged
      120 min/week of moderate to vigorous physical activity (MVPA); 35% had >or=150
      min/week of MVPA. Only 4% accumulated >or=150 min/week of MVPA in bouts >or=10
      min as per public health recommendations. Depressive symptoms, psychological
      distress and cognitive functioning were not associated with physical activity
      (p>.05). Although participants appeared to have substantial minutes of MVPA,
      increased physical activity bouts, or sessions, may be necessary for increased
      health and weight management benefits for persons with severe mental illness.
      Efforts are needed to increase physical activity sessions in this vulnerable
      population.

PMID- 19157788
TI  - Mapping grey matter reductions in schizophrenia: an anatomical likelihood
      estimation analysis of voxel-based morphometry studies.
AB  - Voxel-based morphometry (VBM) is a popular tool for mapping neuroanatomical
      changes in schizophrenia patients. Several recent meta-analyses have identified
      the brain regions in which patients most consistently show grey matter
      reductions, although they have not examined whether such changes reflect
      differences in grey matter concentration (GMC) or grey matter volume (GMV). These
      measures assess different aspects of grey matter integrity, and may therefore
      reflect different pathological processes. In this study, we used the Anatomical
      Likelihood Estimation procedure to analyse significant differences reported in 37
      VBM studies of schizophrenia patients, incorporating data from 1646 patients and
      1690 controls, and compared the findings of studies using either GMC or GMV to
      index grey matter differences. Analysis of all studies combined indicated that
      grey matter reductions in a network of frontal, temporal, thalamic and striatal
      regions are among the most frequently reported in literature. GMC reductions were
      generally larger and more consistent than GMV reductions, and were more frequent
      in the insula, medial prefrontal, medial temporal and striatal regions. GMV
      reductions were more frequent in dorso-medial frontal cortex, and lateral and
      orbital frontal areas. These findings support the primacy of frontal, limbic, and
      subcortical dysfunction in the pathophysiology of schizophrenia, and suggest that
      the grey matter changes observed with MRI may not necessarily result from a
      unitary pathological process.

PMID- 19157789
TI  - Immunoregulatory T cells in the peripheral blood of melanoma patients treated
      with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination.
AB  - BACKGROUND: Regulatory T cells (Treg) may inhibit monocyte-derived melanoma
      antigen-pulsed dendritic cells (DC) vaccination in treatment of melanoma.
      However, the Treg level in peripheral blood mononuclear cells (PBMCs) following
      DC vaccination has not been examined in melanoma patients in Japan. OBJECTIVE: To
      evaluate differences in the helper T cell and Treg population and mRNA levels of
      Treg in pre- and post-DC vaccination PBMCs obtained from melanoma patients.
      METHODS: Levels of intracellular forkhead box protein 3 (Foxp3) mRNA as well as
      levels of CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(+) T cells were examined by real
      time PCR and flow cytometry using PBMCs from 9 patients who received DC
      vaccination. RESULTS: Eight of the 9 cases and 7 of the 9 cases showed increased
      populations of CD4(+)CD25(+) T cells and CD4(+)CD25(+)Foxp3(+) T cells,
      respectively after repeated DC vaccination. Five of 8 cases showed an increase of
      Foxp3 mRNA after treatment. Four of these 5 cases also had increased
      CD4(+)CD25(+) and CD4(+)CD25(+)Foxp3(+) T cells, but the fifth case showed a
      decrease in CD4(+)CD25(+)Foxp3(+) T cells. Three cases showed a decrease of Foxp3
      mRNA. One of these 3 cases showed decreased population of CD4(+)CD25(+)Foxp3(+) T
      cells, but two cases showed increased population of CD4(+)CD25(+)Foxp3(+) T
      cells. In 3 of 8 cases Foxp3 expression at the cellular (protein) and mRNA level
      were inconsistent. CONCLUSION: Repeated DC vaccination may commonly induce Treg
      and helper T cells at the cellular level. However, there are a few discrepancies
      of Treg expression at cellular and mRNA level.

PMID- 19157790
TI  - Decreased heme oxygenase-1 expression in the scalp of patients with alopecia
      areata: the pathogenic role of heme oxygenase-1.

PMID- 19157791
TI  - Association of MIF promoter polymorphisms with psoriasis in a Han population in
      northeastern China.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory
      cytokine that plays an important part in the pathogenesis of autoimmune diseases.
      A high level of MIF has been detected in plaques of psoriasis and the sera of
      patients with psoriasis. Polymorphisms associated with autoimmune and
      inflammatory diseases exist in the promoter region of MIF and alter its
      expression. OBJECTIVE: The aim of this study was to evaluate the potential
      relationship between functional polymorphisms of MIF and psoriasis in a Han
      population in northeastern China. METHODS: Two-hundred-and-forty psoriasis
      patients and a control group of 269 healthy volunteers were included in this
      study. We genotyped MIF-173G/C using polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). MIF-794CATT(5-8) microsatellite
      polymorphism was genotyped by polyacrylamide gel electrophoresis (PAGE). RESULTS:
      No significant difference in the distributions of alleles, genotypes and
      haplotypes was observed between patients and controls. When patients were divided
      into subtypes according to sex, family history and age of onset, distribution of
      the MIF-173C allele between male and female patients was significantly different
      (P=0.04). MIF-173C allelic distribution between late onset psoriasis patients and
      controls was also different (P=0.02), as well as late onset patients and early
      onset subjects (P=0.04). CONCLUSIONS: These results suggested a preliminary
      association between the MIF-173C allele and male psoriasis and late onset
      psoriasis in the studied population. In addition, the distributions of the two
      polymorphisms in Asian populations were quite different from the other
      continental populations.

PMID- 19157792
TI  - Characterization of immortalized human epidermolysis bullosa simplex (KRT5) cell
      lines: trimethylamine N-oxide protects the keratin cytoskeleton against
      disruptive stress condition.
AB  - BACKGROUND: Epidermolysis bullosa simplex (EBS) is an autosomal inherited mechano
      bullous disease, characterized by intraepidermal blistering and skin fragility
      caused by mutations in the keratin (KRT) 5 or 14 genes. Despite a vast knowledge
      about the intermediate filament pathology in this disease, the progress in
      therapy has been slow. Animal models and well-characterized continuous cell
      culture models of EBS are needed prior to clinical testing. OBJECTIVES: Our aim
      was to generate immortalized cell lines as an in vitro model for the study of EBS
      and test a chemical chaperone, trimethylamine N-oxide (TMAO), as a putative novel
      therapy. METHODS: We generated four immortalized cell lines, two each from an EBS
      patient with a KRT5-mutation (V186L) and a healthy control, using human
      papillomavirus 16 (HPV16) E6E7 as transducer. Cell lines were established in
      serum-free and serum-containing medium and assessed for growth characteristics,
      keratin expression profiles, ability to differentiate in organotypic cultures,
      and response to heat stress with and without the presence of TMAO. RESULTS: All
      cell lines have been expanded >160 population doublings and their cellular
      characteristics are similar. However, the formation of cytoplasmic keratin
      filament aggregates in response to heat-shock treatment differed between EBS and
      normal cell lines. Notably, serum-free established EBS-cell line was most
      vulnerable to heat shock but both cell lines exhibited significant reduction in
      the number of keratin aggregates containing cells by TMAO. CONCLUSION: The
      immortalized cell lines represent a suitable model for studying novel therapies
      for EBS. TMAO is a promising new agent for future development as a novel EBS
      therapy.

PMID- 19157793
TI  - Profiling the dysregulated genes of keratinocytes in atopic dermatitis patients:
      cDNA microarray and interactomic analyses.

PMID- 19157794
TI  - Skin application of ketoprofen systemically suppresses contact hypersensitivity
      by inducing CD4(+) CD25(+) regulatory T cells.
AB  - BACKGROUND: Ketoprofen (KP) is a widely used nonsteroidal anti-inflammatory drug
      that inhibits prostaglandin biosynthesis. We have previously shown that topical
      KP treatment at the sensitizing site inhibits the development of contact
      hypersensitivity (CHS) to picryl chloride (PCl). OBJECTIVE: We investigated the
      mechanism underlying the KP-induced immunosuppression of CHS by application of
      KP. METHODS: We analyzed the CHS responses to the non-sensitizing site and
      subsequent sensitization with PCl, and by transfer of the draining lymph node
      cells (LNCs) from KP-tolerated mice to recipient mice. Changes in the Foxp3
      expression of LNCs from KP-phototreated skin were also examined by real-time PCR.
      RESULTS: Topical application of KP to not only the sensitizing but also non
      sensitizing site suppressed CHS response. The immunosuppression was transferred
      with LNCs from mice treated with PCl plus KP, but not from mice treated oxazolone
      plus KP. In this transfer study, the CD4(+) CD25(+) subset of LNCs exerted the
      suppressive effect, while CD25(+) cell-depleted LNCs lost the inhibitory ability.
      CTLA-4 blocking with a specific antibody, but not IL-10 blocking, abrogated the
      activity of CD4(+) CD25(+) cells. Moreover, Foxp3 mRNA expression was remarkably
      increased in LNCs from PCl and KP-treated mice. CONCLUSION: The immunosuppression
      of CHS by topical application of KP is systemic and haptein-specific. Treg cells
      play an important role in the suppressive effect by KP.

PMID- 19157795
TI  - Mutations in the desmoglein 1 gene in five Pakistani families with striate
      palmoplantar keratoderma.
AB  - BACKGROUND: Striate palmoplantar keratoderma (SPPK; OMIM #148700) is a rare
      autosomal dominant genodermatosis characterized by linear hyperkeratosis on the
      digits and hyperkeratosis on the palms and soles. SPPK is known to be caused by
      heterozygous mutations in either the desmoglein 1 (DSG1), desmoplakin (DSP), or
      keratin 1 (KRT1) genes. OBJECTIVE: To define the molecular basis of SPPK in five
      Pakistani families showing a clear autosomal dominant inheritance pattern of
      SPPK. METHODS: Based on previous reports of DSG1 mutations in SPPK, we performed
      direct sequencing of the DSG1 gene of all five families. RESULTS: Mutation
      analysis resulted in the identification of one recurrent mutation (p.R26X) and
      four novel mutations (c.Ivs4-2A>G, c.515C>T, c.Ivs9-3C>G, and c.1399delA) in the
      DSG1 gene. Each mutation is predicted to cause haploinsufficiency of DSG1
      protein. CONCLUSION: The results of our study further underscore the significance
      of the desmoglein gene family in diseases of epidermal integrity.

PMID- 19157796
TI  - Prevalence of obesity/adiposity in Japanese psoriasis patients: adiposity is
      correlated with the severity of psoriasis.

PMID- 19157797
TI  - Effect of berberine on Staphylococcus epidermidis biofilm formation.
AB  - Staphylococcus epidermidis is one of the main causes of medical device-related
      infections owing to its adhesion and biofilm-forming abilities on biomaterial
      surfaces. Berberine is an isoquinoline-type alkaloid isolated from Coptidis
      rhizoma (huang lian in Chinese) and other herbs with many activities against
      various disorders. Although the inhibitory effects of berberine on planktonic
      bacteria have been investigated in a few studies, the capacity of berberine to
      inhibit biofilm formation has not been reported to date. In this study, we
      observed that berberine is bacteriostatic for S. epidermidis and that sub-minimal
      inhibitory concentrations of berberine blocked the formation of S.epidermidis
      biofilm. Using viability assays and berberine uptake testing, berberine at a
      concentration of 15-30mug/mL was shown to inhibit bacterial metabolism. Data from
      this study also indicated that modest concentrations of berberine (30-45mug/mL)
      were sufficient to exhibit an antibacterial effect and to inhibit biofilm
      formation significantly, as shown by the tissue culture plate (TCP) method,
      confocal laser scanning microscopy and scanning electron microscopy for both S.
      epidermidis ATCC 35984 and a clinical isolate strain SE243. Although the
      mechanisms of bacterial killing and inhibition of biofilm formation are not fully
      understood, data from this investigation indicated a potential application for
      berberine as an adjuvant therapeutic agent for the prevention of biofilm-related
      infections.

PMID- 19157798
TI  - Antimicrobial activity of an iron triple helicate.
AB  - The prevalence of antibiotic resistance has resulted in the need for new
      approaches to be developed to combat previously easily treatable infections. Here
      we investigated the potential of the synthetic metallomolecules [Fe(2)L(3)](4+)
      and [Cu(2)(L')(2)](2+) as antibacterial agents. Both molecules have been shown to
      bind DNA; [Fe(2)L(3)](4+) binds in the major groove and causes DNA coiling,
      whilst [Cu(2)(L')(2)](2+) can act as an artificial nuclease. The work described
      here shows that only [Fe(2)L(3)](4+) is bactericidal for Bacillus subtilis and
      Escherichia coli. We demonstrate that [Fe(2)L(3)](4+) binds bacterial DNA in vivo
      and, strikingly, that it kills B. subtilis cells very rapidly.

PMID- 19157799
TI  - Pathogenic potential of vibriophages against an experimental infection with
      Vibrio cholerae O1 in the RITARD model.
AB  - Cholera continues to be an important public health problem in developing
      countries, including India. This study concerns the feasibility of possible
      exploitation of bacteriophages as a biocontrol agent to eliminate the pathogen
      Vibrio cholerae from the gut using the removable intestinal tie-adult rabbit
      diarrhoea (RITARD) model. A control rabbit challenged with 10(9) colony-forming
      units (CFU)/mL of V. cholerae MAK 757 developed Grade II to IV diarrhoea, but the
      phage-treated rabbit that received 10(9)CFU/mL MAK 757 and 10(8) plaque-forming
      units (PFU)/mL cocktail phages produced only Grade II diarrhoea. Histological
      results revealed that in the control rabbit (MAK 757-treated), villi lost their
      normal shape and showed more inflammatory cellular infiltration in the lamina
      propria compared with the experimental rabbit. Our data suggest that phages could
      be valuable as prophylaxis against V. cholerae infection.

PMID- 19157800
TI  - Green tea inhibits Helicobacter growth in vivo and in vitro.
AB  - Helicobacter infection, one of the most common bacterial infections in man
      worldwide, is a type 1 carcinogen and the most important risk factor for gastric
      cancer. Helicobacter pylori bacterial factors, components of the host genetics
      and immune response, dietary cofactors and decreased acid secretion resulting in
      bacterial overgrowth are all considered important factors for induction of
      gastric cancer. Components found in green tea have been shown to inhibit
      bacterial growth, including the growth of Helicobacter spp. In this study, we
      assessed the bactericidal and/or bacteriostatic effect of green tea against
      Helicobacter felis and H. pylori in vitro and evaluated the effects of green tea
      on the development of Helicobacter-induced gastritis in an animal model. Our data
      clearly demonstrate profound growth effects of green tea against Helicobacter
      and, importantly, demonstrate that green tea consumption can prevent gastric
      mucosal inflammation if ingested prior to exposure to Helicobacter infection.
      Research in the area of natural food compounds and their effects on various
      disease states has gained increased acceptance in the past several years.
      Components within natural remedies such as green tea could be further used for
      prevention and treatment of Helicobacter-induced gastritis in humans.

PMID- 19157801
TI  - In vivo impact of the MexAB-OprM efflux system on beta-lactam efficacy in an
      experimental model of Pseudomonas aeruginosa infection.
AB  - In this study, the in vivo impact of the MexAB-OprM efflux system on
      antipseudomonal beta-lactam efficacy was investigated. The respective activities
      of human simulated regimens of ticarcillin (TIC), piperacillin/tazobactam
      (PIP/TAZ) and ceftazidime (CFZ) on two isogenic mutants of Pseudomonas aeruginosa
      PAO1, namely PAO4098E overexpressing MexAB-OprM and PAO4098ET which is OprM
      depleted, were evaluated in an experimental rabbit endocarditis model. The
      following human daily doses by intermittent administration or continuous infusion
      were simulated: 15 g and 18 g for TIC; 12 g and 16 g for PIP/TAZ; and 3g and 6g
      for CFZ. TIC, PIP/TAZ and CFZ exhibited minimum inhibitory concentrations of 64,
      8 and 2 microg/mL, respectively, against PAO4098E and 0.5, 0.5 and 1 microg/mL
      against PAO4098ET. Against PAO4098E, only the high-dose regimens of CFZ were
      effective, with the most significant effect being achieved by continuous
      infusion. In contrast, all the tested regimens were effective against PAO4098ET.
      In the most difficult-to-treat infections due to P. aeruginosa exhibiting the
      efflux system MexAB-OprM, CFZ at high doses and by continuous infusion should be
      preferred to TIC and PIP/TAZ.

PMID- 19157802
TI  - Comparative effects of different cosurfactants on sterile prednisolone acetate
      ocular submicron emulsions stability and release.
AB  - Pluronic F68 is a nonionic, thermogelling block copolymer showing a high
      dehydration resistance during autoclaving due to its high cloud point (>100
      degrees C). Tween 80 (with cloud point of 72.5 degrees C), is a polyoxyethylene
      based cosurfactant, susceptible to temperature because of a decrease in its
      solubility by temperature increase. This study was done to explore whether or
      not, when compared with Tween 80, Pluronic F68 could be used blindly as a
      suitable cosurfactant for the preparation of terminally sterilized ocular
      submicron emulsions containing a lipid soluble drug, prednisolone acetate (PA).
      Various oils of variable viscosities were also tried. The results proved that no
      prediction can be made based on previously known physico-chemical properties
      alone and that emulsion stability depends on the contribution of the various
      emulsion components including: oil, surfactant and cosurfactant, in addition to
      the drug properties.

PMID- 19157803
TI  - Interaction of Oxicam NSAIDs with lipid monolayer: anomalous dependence on drug
      concentration.
AB  - Surface pressure (pi) versus specific molecular area (A) isotherms of Langmuir
      monolayers of dimyristoylphosphatidylcholine (DMPC) lipid on pure water were
      studied in pristine form and in presence of three non-steroidal anti-inflammatory
      drugs, meloxicam (MX), piroxicam (PX) and tenoxicam (TX) in the subphase. Data
      were taken at three drug/lipid (D/L) ratios of 0.026, 0.05, and 0.1. Integration
      of drug to the lipid monolayer was measured by the increase in A (Delta A) of
      DMPC monolayer due to the presence of drugs. All three drugs could be integrated
      in the monolayer resulting in a positive value of Delta A for D/L ratio of 0.026.
      Above this D/L value, there is an anomalous, monotonic decrease in Delta A for MX
      and TX resulting, finally, in negative Delta A values. For PX, however, decrease
      in Delta A values at D/L of 0.05 is partially compensated at D/L of 0.1. We have
      tentatively explained these observations by invoking two competing forces in the
      overall drug-lipid interaction. One of these is an 'in-plane' force that tends to
      integrate the drug molecule to the plane formed by the lipid monolayer and the
      other is an 'out-of-plane' force that perturbs the drug and the lipid molecules
      such that the monolayer plane is no longer well defined.

PMID- 19157804
TI  - Hemocompatibility and cytocompatibility of styrenesulfonate-grafted PDMS
      polyurethane-HEMA hydrogel.
AB  - Copolymerization of polydimethylsiloxane, polyurethane, and hydroxyethyl
      methacrylate (PDMS-PU-HEMA) hydrogel was performed. After treating with oxygen
      plasma, the sodium salt of 4-styrenesulfonic acid (NASS) was grafted onto the
      hydrogel in a one-step process. The surface density of peroxide active groups was
      determined by the iodide method. The hydrophilicity of the hydrogels surface was
      evaluated by measuring the water contact angle and water retention. The result
      demonstrated that oxygen plasma treatment and NASS grafting can improve the
      hydrophilicity. In addition, in order to evaluate cell compatibility, L929
      fibroblasts cells were cultured on the surface of these hydrogels and the cell
      number was determined by the MTT testing. The results show that plasma treatment
      and NASS grafting can cause higher cell adhesion and cell growth rates than
      untreated PDMS-PU-HEMA. Furthermore, NASS grafting can also reduce the platelet
      adhesion and protein adsorption, hence effectively extending the blood
      coagulation times. Consequently hydrophilicity, cytocompatibility and
      hemocompatibility were greatly enhanced by the NASS grafting of PDMS-PU-HEMA.

PMID- 19157805
TI  - Influence of zeolite PZC and pH on the immobilization of cytochrome c: a
      preliminary study regarding the preparation of new biomaterials.
AB  - The adsorption of cytochrome c on to zeolite crystals and membranes with
      different chemical composition and structure was studied. The structure and
      texture of zeolite materials were identified by X-ray diffraction (XRD) and
      scanning electron microscopy (FESEM), while the variation of protein conformation
      was studied by Fourier transform infrared attenuated total reflectance (FTIR-ATR)
      analysis. In order to separate the influence of zeolite structures from the
      effect of composite membranes, a through analysis of the cytochrome c adsorption
      was performed on different crystals by varying several experimental parameters
      such as: pH value, protein amount, zeolite structures and chemical compositions.
      It is shown that the electrostatic type of interaction seems to be of the utmost
      importance to govern the immobilization, while the zeolite Bronsted acidity of
      the support is the subordinate parameter which differentiates the adsorption
      performances of different zeolite structures (that distinct for chemical
      composition of the framework).

PMID- 19157806
TI  - Anisotropic diffusion deviates chicken embryo chorioallantoic membrane assay
      (CAM) to reflect inherent therapeutic behaviors.
AB  - Chorioallantoic membrane assay (CAM) has become a widely used tool for
      determination of anti-angiogenesis capability of many drugs including herbal
      extracts. Because varying results in same set of chicken embryos are often
      encountered, we developed the complex diffusion model that combined the Fick's
      second diffusion law, chemical-protein interaction (or binding) to explain the
      diffusion- or kinetic-limiting phenomena in egg white when performing CAM. In
      addition, we performed diffusion studies in egg white with Color Blue No. 1,
      Evans Blue, Color Red No. 40, and the aqueous extract of Psidium guajava budding
      leaves (PE) to support our model. Under same conditions, the diffusion
      coefficients of Blue No. 1, Evans Blue, Red No. 40, and PE were (2.0-2.8)x10(-9),
      (0.89-31)x10(-9), (2.8-12)x10(-9), and (7.0-21)x10(-9)m(2)s(-1), respectively,
      depending upon the distance diffused. Whilst at the interface of egg white and
      embryo (egg yolk), a site about 1cm apart from the aeration sac, the percent
      concentration reached only 10.5, 3.0, 3.6, and 2.2% of the original applied
      medicine, respectively. We conclude that CAM could only serve as a preliminary
      screening tool for angiogenesis, because the anisotropic diffusion in egg white
      affects greatly the effective dosages of medicines tested.

PMID- 19157807
TI  - Direct detection of carcinoembryonic antigen autoantibodies in clinical human
      serum samples using a surface plasmon resonance sensor.
AB  - The ability to detect biomarkers in human serum is important for cancer
      diagnostics. The work presented focuses on the establishment of a surface plasmon
      resonance (SPR) biosensor as a means for detecting varying levels of autoantibody
      biomarkers in human serum samples. Carcinoembryonic antigen (CEA) is a biomarker
      that is present in human serum. It is thought that CEA levels become elevated in
      patients with colon and ovarian cancer, causing a corresponding increase in the
      autoantibody level in human serum. Detection of this CEA autoantibody increase
      could be used to diagnose cancer in patients. Using a SPR biosensor, human serum
      samples were screened directly for CEA antibody levels. Results using a sandwich
      assay with a SPR sensor demonstrated the same linear trend as seen from an
      established enzyme-linked immunosorbent assay (ELISA) method. Serum samples from
      five healthy individuals were used to establish a threshold value for
      differentiating a cancerous serum sample from a negative sample with a 95%
      confidence. Three serum samples from cancer patients with positive CEA antibody
      levels as evaluated by ELISA were used to test the criterion.

PMID- 19157808
TI  - Self-assembly nano-structure of type I collagen adsorbed on Gemini surfactant LB
      monolayers.
AB  - The self-assembly nano-structures of type I collagen adsorbed on anionic Gemini
      surfactant LB monolayer were observed by using atomic force microscopy (AFM)
      images. It was found that the adsorption behavior and self-assembly structure of
      collagen could be controlled by the concentration of the collagen solution,
      adsorption interval and the properties of substrates. With the increase of the
      adsorption interval and concentration of collagen, the strands size of collagen
      changed. The self-assembly structures of collagen were also influenced by the
      interaction between collagen molecules and Gemini surfactant monolayer
      substrates. Finally, the adsorption behaviors of collagen molecules on cationic
      Gemini monolayer were compared with those on anionic Gemini monolayer.

PMID- 19157809
TI  - [Torticollis revealing Wilson's disease].

PMID- 19157810
TI  - Nuclearia thermophila sp. nov. (Nucleariidae), a new nucleariid species isolated
      from Yunoko Lake in Nikko (Japan).
AB  - A new species of unicellular opisthokont protist, Nuclearia thermophila sp. nov.,
      was isolated from the warm spring water of Yunoko Lake, Japan, and has been
      described using light and electron microscopy. It exists as a spherical floating
      form and a flattened amoeboid form showing various shapes. The cells occasionally
      extended as branches or knobbed filopodia. The spherical form when suspended in
      medium measured 20-40microm in diameter (excluding filopodia). The amoeboid form
      may exceed 65microm along the longest axis. A nucleus with an obvious spherical
      nucleolus, dictyosomes, mitochondria with flat cristae, food vacuoles, and lipid
      droplet-like vacuoles with homogeneous contents were observed; no extracellular
      matrix or bacterial endosymbionts were present. The cells ingested flour
      particles. No cysts were seen. The molecular phylogenetic tree constructed on the
      basis of the small subunit ribosomal DNA revealed the novelty of N. thermophila
      and its relationships with previously known nucleariids.

PMID- 19157812
TI  - An application of methods for the probabilistic three-class classification of
      pregnancies of unknown location.
AB  - OBJECTIVE: We developed and compared classifiers to predict the outcome of
      pregnancies of unknown location (PUL). This is a three-class problem, as the
      possible outcomes are failing PUL, intra-uterine pregnancy (IUP), or ectopic
      pregnancy (EP). We focused on probabilistic classification because of the
      importance of uncertainty information in medical decision making. METHODS AND
      MATERIALS: Nine methods were implemented, based on logistic regression (LR),
      multi-layer perceptrons, least squares support vector machines (LS-SVMs), and
      kernel logistic regression (KLR). The LR models involved manual checks for the
      necessity of input transformations or interaction effects. The classifiers were
      developed on the training set (n=508) and evaluated on the test set (n=348). We
      used two performance measures that only evaluate discriminatory potential, and
      two that investigate the exact probabilities and/or discriminatory potential.
      Classifier comparison was carried out using a ranking method. RESULTS: The
      classifier based on a combination of binary LR models using pairwise coupling (LR
      PC) ranked first or second for each performance measure. LR-PC obtained test set
      areas under the receiver operating characteristic curve of 0.989, 0.988, and
      0.924 for the prediction of failing PULs, IUPs, and EPs, respectively. Multi
      class LR, multi-class KLR, and a combination of binary Bayesian LS-SVMs with
      radial basis function kernel were always ranked in the top five. Models with low
      emphasis on nonlinearity were ranked at the bottom. Importantly, LR-PC also
      performed better than previously developed classifiers based on multi-class LR.
      CONCLUSIONS: The prediction of PULs was good, most notably for failing PULs and
      IUPs. Logistic regression models performed remarkably well. Multi-class KLR also
      performed well, whilst nonlinearity was automatically incorporated and
      probabilistic outputs were directly given without Bayesian analysis or a
      combination of binary results. The selected inputs are reasonably objective and
      easy to obtain in clinical practice. Taken together, this study provided useful
      decision support tools for implementation in clinical practice.

PMID- 19157811
TI  - A decision aid for intensity-modulated radiation-therapy plan selection in
      prostate cancer based on a prognostic Bayesian network and a Markov model.
AB  - OBJECTIVE: The prognosis of cancer patients treated with intensity-modulated
      radiation-therapy (IMRT) is inherently uncertain, depends on many decision
      variables, and requires that a physician balance competing objectives: maximum
      tumor control with minimal treatment complications. METHODS: In order to better
      deal with the complex and multiple objective nature of the problem we have
      combined a prognostic probabilistic model with multi-attribute decision theory
      which incorporates patient preferences for outcomes. RESULTS: The response to
      IMRT for prostate cancer was modeled. A Bayesian network was used for prognosis
      for each treatment plan. Prognoses included predicting local tumor control,
      regional spread, distant metastases, and normal tissue complications resulting
      from treatment. A Markov model was constructed and used to calculate a quality
      adjusted life-expectancy which aids in the multi-attribute decision process.
      CONCLUSIONS: Our method makes explicit the tradeoffs patients face between
      quality and quantity of life. This approach has advantages over current
      approaches because with our approach risks of health outcomes and patient
      preferences determine treatment decisions.

PMID- 19157813
TI  - The utility of publicly reported cancer treatment wait time information for
      patients and health care providers.
AB  - AIMS: To determine the utility of web-based radiation wait time information for
      patients and health care providers in decision-making. To revise the information
      using a simulated laboratory environment and to re-evaluate the new web-based
      information. MATERIALS AND METHODS: An online 'pop-up' survey on the Cancer Care
      Ontario (CCO) website measured user satisfaction. Qualitative data were gathered
      through patient focus groups and physician interviews. On the basis of the
      analysis, the website was revised and usability testing conducted. The
      information was re-evaluated by end-users through survey methodology. RESULTS:
      The majority accessing the wait time website were patients and family members.
      The modal age of use of the website was 31-50 years. Patients found the
      information more helpful after redesign than health professionals, but both found
      the language less easy to understand, highlighting the need to continuously
      evaluate the effectiveness of the website. Patients did not identify themselves
      as consumers of wait time information. Their expectation was that physicians
      would determine the urgency for treatment and would ensure timely access to care.
      Physicians reported that they did not use the CCO website on wait times and would
      not use the data for decision-making. Referrals were based on urgency of care and
      usual referral patterns. Referral patterns did not shift to centres with shorter
      wait times. CONCLUSIONS: The results of this study did not confirm the usefulness
      of the web-based wait time information for patients and physicians as a resource
      on how to obtain timely access to radiation treatment. Patients relied on their
      physician to manage their access to treatment according to the urgency of their
      clinical condition. Physicians preferred their established referral process
      rather than referring their patients to centres with shorter wait times. As
      patients become more computer savvy, it will be interesting to see if they
      increasingly become consumers of web-based wait time information.

PMID- 19157814
TI  - Indium-labelled autologous dendritic cells migrate to local lymph nodes after
      intratumoural injection in head and neck cancer patients.

PMID- 19157815
TI  - Polyphenol-containing azuki bean (Vigna angularis) extract attenuates blood
      pressure elevation and modulates nitric oxide synthase and caveolin-1 expressions
      in rats with hypertension.
AB  - BACKGROUND AND AIMS: Azuki beans (Vigna angularis) contain polyphenols such as
      proanthocyanidins that exhibit potential radical scavenging activities. We herein
      investigated the effects of polyphenol-containing azuki bean extract (ABE) on
      elevated blood pressure, nitric oxide (NO) production, and expressions of
      endothelial NO synthase (eNOS), inducible NOS (iNOS), and caveolin-1 proteins in
      the aorta and kidney of chronically hypertensive rats. METHODS AND RESULTS:
      Spontaneously hypertensive rats (SHRs/Izm) with approximately 200 mm Hg systolic
      blood pressure (SBP) were randomly divided into 2 groups fed either 0% or 0.9%
      ABE-containing diet. Age-matched normotensive Wistar-Kyoto rats were used as the
      control. The content of 24-h urinary nitrate/nitrite (NOx) excretion was measured
      to evaluate NO production. After 8 weeks of treatment, the eNOS, iNOS, and
      caveolin-1 protein expressions in the aorta and kidney were analyzed by western
      blotting. The SBP of the ABE-treated SHR was significantly lower than that of the
      untreated SHR. The level of 24-h urinary NOx excretion was significantly higher
      in the ABE-treated SHR than in the untreated SHR. The eNOS and iNOS expressions
      in the aorta and kidney were remarkably upregulated in the untreated SHR but
      suppressed in the ABE-treated SHR. The vascular and renal caveolin-1 expressions
      were upregulated in the ABE-treated SHR. CONCLUSIONS: ABE reduced the elevated
      blood pressure and increased NO production in long-term treatment. It may be
      associated with the modulation of eNOS and iNOS protein expressions in the aorta
      and kidney during the development of hypertension.

PMID- 19157816
TI  - Viscosity of fiber preloads affects food intake in adolescents.
AB  - BACKGROUND AND AIMS: Dietary fiber that develops viscosity in the
      gastrointestinal tract is capable of addressing various aspects of food intake
      control. The aim of this study was to assess subsequent food intake and appetite
      in relation to the level of viscosity following three liquid preloads each
      containing 5 g of either a high (novel viscous polysaccharide; NVP), medium
      (glucomannan; GLM), or low (cellulose; CE) viscosity fiber. METHODS AND RESULTS:
      In this double-blind, randomized, controlled and crossover trial, 31 healthy
      weight adolescents (25 F:6 M; age 16.1+/-0.6 years; BMI 22.2+/-3.7 kg/m(2))
      consumed one of the three preloads 90 min prior to an ad libitum pizza meal.
      Preloads were identical in taste, appearance, nutrient content and quantity of
      fiber, but different in their viscosities (10, 410, and 700 poise for CE, GLM,
      and NVP, respectively). Pizza intake was significantly lower (p=0.008) after
      consumption of the high-viscosity NVP (278+/-111 g) compared to the medium
      viscosity GLM (313+/-123 g) and low-viscosity CE (316+/-138 g) preloads, with no
      difference between the GLM and CE preloads. Appetite scores, physical symptoms
      and 24-h intake did not differ among treatment groups. CONCLUSION: A highly
      viscous NVP preload leads to reduced subsequent food intake, in terms of both
      gram weight and calories, in healthy weight adolescents. This study provides
      preliminary evidence of an independent contribution of viscosity on food intake
      and may form a basis for further studies on factors influencing food intake in
      adolescents.

PMID- 19157817
TI  - Reproducibility patterns of plasma norepinephrine and muscle sympathetic nerve
      traffic in human obesity.
AB  - BACKGROUND AND AIMS: The present study was designed to assess the reproducibility
      of the two markers of adrenergic drive, venous plasma norepinephrine and efferent
      postganglionic muscle sympathetic nerve traffic (MSNA) in reflecting the
      sympathetic activation characterizing the obese state in human beings. METHODS
      AND RESULTS: In 15 male obese normotensive subjects (age: 40.1+/-2.2, mean+/-SEM)
      we measured, in two experimental sessions three weeks apart, blood pressure (BP,
      Finapres), heart rate (EKG), plasma norepinephrine (HPLC assay) and MSNA
      (microneurography, peroneal nerve). In each session three norepinephrine samples
      were obtained and norepinephrine reproducibility between sessions was assessed by
      considering a single norepinephrine sample or by averaging 2-3 samples.
      Reproducibility data were compared to the ones displayed by the MSNA technique.
      While MSNA values showed a highly significant correlation between sessions
      (r=0.89, p<0.001), norepinephrine values based on a single blood sample
      evaluation did not correlate with each other (r=0.44, p=NS). Norepinephrine
      correlation coefficient values increased and achieved statistical significance
      when average data from 3 blood samples were examined (r=0.56, p<0.03).
      CONCLUSIONS: In human obesity MSNA displays a reproducibility pattern higher than
      plasma norepinephrine. The reproducibility of the norepinephrine approach can be
      improved by increasing the number of blood samples on which norepinephrine assay
      is performed. To obtain such a goal, and to make reproducibility closer to the
      MSNA one, three norepinephrine samples are needed.

PMID- 19157818
TI  - High prevalence of subclinical cardiovascular abnormalities in patients with
      systemic lupus erythematosus in spite of a very low clinical damage index.
AB  - BACKGROUND AND AIM: To evaluate the prevalence of subclinical cardiovascular (CV)
      abnormalities in systemic lupus erythematosus (SLE) stratified according to SLE
      related organ damage using the Systemic Lupus International Collaborating Clinics
      (SLICC) damage index. METHODS AND RESULTS: We selected SLE patients without
      clinically overt CV events (n=45, 56% with SLICC=0, 44% with SLICC=1-4). CV
      evaluation was performed using cardiac and vascular echo-Doppler techniques. Post
      ischemic flow-mediated dilation (FMD) over nitroglycerine-mediated dilation (NMD)
      of the brachial artery <0.70 defined endothelial dysfunction. The prevalence of
      preclinical CV abnormalities (CVAbn, including at least one of the following
      carotid atherosclerosis, left ventricular (LV) hypertrophy, low arterial
      compliance, LV wall motion abnormalities, aortic regurgitation, FMD/NMD<0.70)-was
      64% (16/25) in patients with SLICC=0 and 80% (16/20) in those with SLICC>0 (p=not
      significant (NS)). In particular, the prevalence of carotid atherosclerosis (28%
      vs. 16%), of LV hypertrophy (12% vs. 6%) and of LV wall motion abnormalities (15%
      vs. 12%), of low global arterial compliance (18% vs. 10%), prevalence of aortic
      regurgitation (30% vs. 18%) and/or aortic valve fibrosclerosis (10% vs. 8%),
      FMD<10% (14+/-5% vs. 14%+/-6) and prevalence of FMD/NMD<0.70 (53% vs. 52%) were
      comparable in SLE patients with SLICC>0 and in those with SLICC=0 (all p=NS). Of
      the SLE patients without carotid atherosclerosis, LV hypertrophy, low arterial
      compliance, LV wall motion abnormalities and aortic regurgitation (n=17),
      endothelial dysfunction was detected in 50% of those with SLICC=0 (6/12) and in
      40% of those with SLICC>0 (2/5, p=NS). CONCLUSIONS: SLE patients with SLICC=0
      often have an elevated CV risk profile due to subclinical manifestations of CV
      disease detectable by cardiac and vascular echo-Doppler evaluations.

PMID- 19157820
TI  - A potential proliferative gene, NUDT6, is down-regulated by green tea catechins
      at the posttranscriptional level.
AB  - The main aims of this study were to elucidate the effect of green tea catechins
      on Nudix-type motif 6 (NUDT6) suppression and to characterize NUDT6's biological
      activity. Our microarray data showed that the green tea component epicatechin-3
      gallate suppressed NUDT6 expression, and this was confirmed by RT-PCR.
      Subsequently, the use of different catechins showed that the effect of
      epigallocatechin-3-gallate (EGCG) was stronger than that of other catechins. At
      the posttranscriptional level, EGCG decreased the RNA stability of NUDT6,
      indicating it as a potential mechanism of NUDT6 suppression. Further cloning of
      the 3' untranslated region of human NUDT6 mRNA resulted in reduced luciferase
      activity by EGCG treatment. This effect was at least, in part, mediated by the
      extracellular-signal-regulated kinase and p38MAPK pathways. Finally, increased
      cell proliferation and cell growth in soft agar were observed in NUDT6
      overexpressing cells. These findings provide a novel mechanism for the
      suppression of the proliferative gene NUDT6 by green tea catechins in human
      colorectal cancer.

PMID- 19157821
TI  - Gender affects liver desaturase expression in a rat model of n-3 fatty acid
      repletion.
AB  - Dietary n-3 polyunsaturated fatty acids (PUFA) are major components of cell
      membranes and have beneficial effects on human health. Docosahexaenoic acid (DHA;
      22:6n-3) is the most biologically important n-3 PUFA and can be synthesized from
      its dietary essential precursor, alpha-linolenic acid (ALA; 18:3n-3). Gender
      differences in the efficiency of DHA bioconversion have been reported, but
      underlying molecular mechanisms are unknown. We compared the capacity for DHA
      synthesis from ALA and the expression of related enzymes in the liver and
      cerebral cortex between male and female rats. Wistar rats, born with a low-DHA
      status, were supplied with a suboptimal amount of ALA from weaning to 8 weeks of
      age. Fatty acid composition was determined by gas chromatography, the mRNA
      expression of different genes involved in PUFA metabolism was determined by RT
      PCR (low-density array) and the expression of proteins was determined by Western
      blot analysis. At 8 weeks, DHA content was higher (+20 to +40%) in each
      phospholipid class of female livers compared to male livers. The "Delta4," Delta5
      and Delta6 desaturation indexes were 1.2-3 times higher in females than in males.
      The mRNA expression of Delta5- and Delta6-desaturase genes was 3.8 and 2.5 times
      greater, respectively, and the Delta5-desaturase protein was higher in female
      livers (+50%). No gender difference was observed in the cerebral cortex. We
      conclude that female rats replete their DHA status more readily than males,
      probably due to a higher expression of liver desaturases. Our results support the
      hypothesis on hormonal regulation of PUFA metabolism, which should be taken into
      account for specific nutritional recommendations.

PMID- 19157822
TI  - S-allylcysteine modulates the expression of E-cadherin and inhibits the malignant
      progression of human oral cancer.
AB  - Oral cancer is a prevalent type of cancer in Asian countries. Several studies
      indicated that garlic extracts such as diallyl disulfide (DADS) and diallyl
      trisulfide (DATS) have anticancer effects. However, the inhibitory effects of
      water soluble garlic extracts, S-allylcysteine (SAC), on the malignant
      progression of oral cancer have not been studied well yet. Thus, the purpose of
      this study was to investigate the inhibitory effects of SAC on the proliferation
      and progression of human oral squamous cancer CAL-27 cells. In the present study,
      we demonstrated that SAC dose dependently inhibited the growth of human oral
      squamous cancer cells. Our results showed that SAC induced the expression of E
      cadherin adhesion molecule. Immunocytochemical staining result also revealed that
      SAC could restore the distribution of E-cadherin molecule on cell membrane. We
      further demonstrated that SAC stabilized the adherent junction complex of E
      cadherin/beta-catenin in oral cancer cells. Treatment with the MAPK/MEK specific
      inhibitor, PD098059, could up-regulate the expression of E-cadherin molecule.
      Furthermore, SAC significantly inhibited the activation of MAPK/ERK signaling
      pathway. These findings were associated with the down-regulation of the SLUG
      repressor protein. In conclusion, our results indicated that SAC effectively
      inhibited the proliferation, up-regulated the expression of E-cadherin molecule
      and stabilized the E-cadherin/beta-catenin adherent junction complex in human
      oral squamous cancer cells. The mechanism of action was in part through the
      suppression of MAPK/ERK signaling pathway and down-regulation of the SLUG
      repressor protein.

PMID- 19157823
TI  - Regional differences in the expression of genes involved in lipid metabolism in
      adipose tissue in response to short- and medium-term fasting and refeeding.
AB  - The aim of this study was to analyze regional differences in the time-course
      response to fasting and refeeding in the expression of genes involved in lipid
      metabolism in retroperitoneal, mesenteric and inguinal adipose tissue. Rats were
      studied under different feeding conditions: feeding state; after 4, 8 or 24 h of
      fasting; and after 3 h of refeeding following 8 h of fasting. The expression of
      lipogenesis-related genes decreased by fasting in adipose tissue, and the
      retroperitoneal depot showed the fastest response: mRNA levels of peroxisome
      proliferator-activated receptor gamma 2 (PPARgamma2) decreased after 4 h of
      fasting and those of sterol regulatory element binding protein 1c (SREBP1c),
      fatty acid synthase (FAS), GPAT and glucose transporter 4 (GLUT4) decreased after
      8 h. In the inguinal depot, mRNA levels of SREBP1c, acetyl-coenzyme A carboxylase
      alpha, FAS and lipoprotein lipase decreased after 8 h of fasting, while in the
      mesenteric depot, only GLUT4 and FAS mRNA levels decreased after 8 and 24 h,
      respectively. Concerning lipolytic and fatty acid oxidation genes, only adipose
      triglyceride lipase and carnitine palmitoyltransferase 1a expression increased
      after 24 h of fasting in the retroperitoneal depot. Three hours of refeeding
      restored the expression of the lipogenic transcription factors PPARgamma2 and
      SREBP1c in the retroperitoneal depot and of PPARgamma2 in the inguinal depot.
      This period of refeeding was ineffective in changing the expression of genes
      related with lipid mobilization and fatty acid oxidation, except hormone
      sensitive lipase, whose expression decreased in the mesenteric depot. It is
      suggested that different regulations of the expression of genes related with
      lipid metabolism between internal and subcutaneous depots to feeding and fasting
      conditions are site-specific metabolic features of white adipose tissue.

PMID- 19157824
TI  - Dietary enrichment with wild blueberries (Vaccinium angustifolium) affects the
      vascular reactivity in the aorta of young spontaneously hypertensive rats.
AB  - We have previously reported on the positive effects of wild blueberries on
      arterial contractile response to alpha(1) adrenergic stimuli and on endothelium
      mediated vasorelaxation. Our present study was designed to evaluate the effects
      of the dietary enrichment with wild blueberries on aortic function and reactivity
      in the developmental phase of essential hypertension in spontaneously
      hypertensive rats (SHR). We investigated the possible influence blueberries may
      have on the acetylcholine (Ach)-induced endothelium-dependent vasorelaxation and
      phenylephrine-induced vasoconstriction in young SHRs, as well as the contribution
      of the nitric oxide (NO) synthase and cyclooxygenase (COX) pathways in each of
      the above responses in an animal model with dysfunctional endothelium. Vascular
      ring studies were conducted in 3-mm isolated rat aortic ring preparations to
      investigate vasoconstriction induced by l-Phenylephrine (Phe, 10(-8) to 3x10(
      6)M) and vasorelaxation induced by acetylcholine (Ach, 10(-9) to 3x10(-6)M). The
      major findings of our study were that in Phe-induced vasoconstriction, SHR-BB
      aortas relaxed to a greater degree in comparison to controls when mefenamic acid
      (MFA) was present and that the incubation with this COX inhibitor failed to
      restore - and in fact decreased - the maximum vasodilator response to Ach, in
      comparison to controls. Our vessel reactivity index (pD(2)) observations indicate
      that blueberries appear to modulate cell membrane-agonist (Ach) interactions
      primarily in response to Ach in the young SHR model, but not to the alpha(1)
      adrenoreceptor agonist. Incorporating wild blueberries in the diet seems to
      affect the endothelium-dependent vasorelaxation by modulating alternative
      metabolic pathway(s) (such as affecting the production/activity of COX-derived
      products) in the young SHR aorta.

PMID- 19157825
TI  - Licorice isoliquiritigenin dampens angiogenic activity via inhibition of MAPK
      responsive signaling pathways leading to induction of matrix metalloproteinases.
AB  - The aberrant expression of matrix metalloproteinases (MMPs) has been implicated
      in matrix degradation leading to angiogenesis. This study examined the inhibitory
      effects of isoliquiritigenin (ISL) on phorbol myristate acetate (PMA)-induced MMP
      production and its tissue inhibitor of MMP (TIMP) in endothelial cells. No
      induction of either necrotic or apoptotic cell death was observed in response to
      a treatment with ISL at <or=25 microM. ISL dose-dependently suppressed PMA
      induced expression and activity of MMP-2 and membrane type 1-MMP at >or=1 microM
      while diminishing the elevated MMP-2 transcript level. In addition, ISL inhibited
      PMA-triggered migration and tube formation in a dose-dependent manner. ISL
      further increased the TIMP production up-regulated by PMA with a biphasic effect
      on TIMP-2 expression. This study further attempted to investigate whether a c-Jun
      N-terminal kinase (JNK)- or p38 mitogen-activated protein kinase (MAPK)
      responsive mechanism was responsible for the MMP production and whether ISL
      disturbed these signaling pathways. PMA stimulated signaling of JNK and p38 MAPK,
      which was dampened by >or=10 microM ISL. These results demonstrate that ISL
      blocked JNK- or p38 MAPK-responsive pathways leading to direct MMP activation of
      PMA-exposed endothelial cells. Therefore, the ISL inhibition of MMP may boost a
      therapeutic efficacy during angiogenesis.

PMID- 19157826
TI  - The role of alpha-tocopherol in motor hypofunction with aging in alpha-tocopherol
      transfer protein knockout mice as assessed by oxidative stress biomarkers.
AB  - It has been hypothesized that oxidative stress plays a key role in aging. In
      order to elucidate the role of the antioxidant network - including alpha
      tocopherol (alphaT) and alphaT transfer protein - in aging in vivo, alpha
      tocopherol transfer protein knockout (alphaTTP(-/-)) mice were fed a vitamin-E
      depleted diet, and wild-type (WT) mice were fed a diet containing 0.002 wt.%
      alphaT from the age of 3 months to 1 1/2 years. The lipid oxidation markers total
      hydroxyoctadecadienoic acid (tHODE) and 8-iso-prostaglandin F(2)alpha, and
      antioxidant levels in the blood, liver and brain were measured at 3, 6, 12 and 18
      months. tHODE levels in the plasma of alphaTTP(-/-) mice were elevated at 6
      months compared to 3 months, and were significantly higher those in WT mice,
      although they decreased thereafter. On the other hand, tHODE levels in the liver
      and brain were constantly higher in alphaTTP(-/-) mice than in WT mice. Motor
      activities decreased with aging in both mouse types; however, those in the
      alphaTTP(-/-) mice were lower than those in the WT mice. It is intriguing to note
      that motor activities were significantly correlated with the stereoisomer ratio
      (Z,E/E,E) of HODE, which is a measure of antioxidant capacity in vivo, in the
      plasma, in the liver and even in the brain, but not with other factors such as
      antioxidant levels. In summary, using the biomarker tHODE and its stereoisomer
      ratio, we demonstrated that alphaT depletion was associated with a decrease in
      motor function, and that this may be primarily attributable to a decrease in the
      total antioxidant capacity in vivo.

PMID- 19157827
TI  - The effect of high-amylose cornstarch on lipid metabolism in OVX rats is affected
      by fructose feeding.
AB  - We examined whether the effects of high-amylose cornstarch (HACS) on lipid
      metabolism in ovariectomized (OVX) rats were affected by high-fructose feeding.
      Sucrose (482 g/kg diet) was used as fructose source. OVX rats were fed one of the
      following four diets for 21 days: a sucrose-based or cornstarch-based cholesterol
      free diet with or without HACS (150 g/kg diet). Body weight and food intake were
      increased by sucrose. Plasma total cholesterol and low-density lipoprotein
      cholesterol concentrations were increased by sucrose and decreased by HACS in
      cornstarch-fed rats, but not in sucrose-fed rats. Liver total lipids and
      concentrations of plasma and liver triacylglycerol (TAG) were increased by
      sucrose, whereas plasma TAG concentration was decreased by HACS, in sucrose-fed
      rats. However, liver cholesterol concentration was not affected by diet. The
      amount of cholesterol in small-intestinal contents was increased in sucrose-fed
      rats, but not in cornstarch-fed rats, but that of bile acids was not affected by
      diet. Fecal excretions of bile acids and neutral sterols were increased by HACS.
      The level of sterol-regulatory element-binding protein-1c mRNA was increased by
      sucrose and decreased by HACS in sucrose-fed rats, but not in cornstarch-fed
      rats. The level of farnesoid X receptor mRNA was decreased by sucrose and
      increased by HACS in cornstarch-fed rats, but not in sucrose-fed rats, as was the
      level of cholesterol 7alpha-hydroxylase mRNA. These results show that the effect
      of HACS on hyperlipidemia induced by ovarian hormone deficiency would be affected
      by the consumption of fructose-rich sweeteners such as sucrose and high-fructose
      syrup.

PMID- 19157828
TI  - Oligomerized grape seed polyphenols attenuate inflammatory changes due to
      antioxidative properties in coculture of adipocytes and macrophages.
AB  - Macrophage infiltration of white adipose tissue (WAT) is implicated in the
      metabolic complications of obesity. In addition, inflammatory changes through
      dysregulated expression of inflammation-related adipokines such as tumor necrosis
      factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) in WAT
      are considered to be one of the causes of insulin resistance. Recently, enhanced
      oxidative stress in adipocytes has been reported to be implicated in dysregulated
      expression of inflammation-related adipokines. Polyphenols are well known as
      potent natural antioxidants in the diet. In the present study, we investigated
      the antioxidative effects of an oligomerized grape seed polyphenol (OGSP) on
      inflammatory changes in coculture of adipocytes and macrophages. Coculture of HW
      mouse white adipocytes and RAW264 mouse macrophages markedly increased the
      production of TNF-alpha, MCP-1 and plasminogen activator inhibitor-1 compared
      with control culture. Treatment of HW cells with OGSP significantly attenuated
      the dysregulated production of adipokines. Moreover, OGSP significantly
      suppressed coculture-induced production of reactive oxygen species (ROS).
      Although enhanced release of free fatty acids (FFAs) by coculture was not altered
      by OGSP, FFA-induced ROS production in HW cells was significantly attenuated by
      OGSP. Furthermore, OGSP significantly reduced increases in the transcriptional
      activity of nuclear factor-kappaB and activation of extracellular signal
      regulated kinase by coculture. Thus, these results suggest that the antioxidative
      properties of OGSP attenuate inflammatory changes induced by the coculture of
      adipocytes and macrophages.

PMID- 19157829
TI  - Lycopene prevents 7-ketocholesterol-induced oxidative stress, cell cycle arrest
      and apoptosis in human macrophages.
AB  - The present study was undertaken to examine whether lycopene is able to
      counteract 7-ketocholesterol (7-KC)-induced oxidative stress and apoptosis in
      human macrophages. Human THP-1 macrophages were exposed to 7-KC (10-25 microM)
      alone and in combination with lycopene (0.5-2 microM), and we monitored changes
      in cell oxidative status [reactive oxygen species (ROS) production, NOX-4, hsp70
      and hsp90 expressions, 8-OHdG formation] and in cell proliferation and apoptosis.
      After 24 h of treatment, lycopene significantly reduced the increase in ROS
      production and in 8-OHdG formation induced by the oxysterol in a dose-dependent
      manner. Moreover, the carotenoid strongly prevented the increase of NOX-4, hsp70
      and hsp90 expressions as well as the phosphorylation of the redox-sensitive p38,
      JNK and ERK1/2 induced by the oxysterol. The attenuation of 7-KC-induced
      oxidative stress by lycopene coincided with a normalization of cell growth in
      human macrophages. Lycopene prevented the arrest in G0/G1 phase of cell cycle
      induced by the oxysterol and counteracted the increased expression of p53 and
      p21. Concomitantly, it inhibited 7-KC-induced apoptosis, by limiting caspase-3
      activation and the modulatory effects of 7-KC on AKT, Bcl-2, Bcl-xL and Bax.
      Comparing the effects of lycopene, beta-carotene and (5Z)-lycopene on ROS
      production, cell growth and apoptosis show that lycopene and its isomer were more
      effective than beta-carotene in counteracting the dangerous effects of 7-KC in
      human macrophages. Our study suggests that lycopene may act as a potential
      antiatherogenic agent by preventing 7-KC-induced oxidative stress and apoptosis
      in human macrophages.

PMID- 19157830
TI  - Spectroscopic characterization of organic matter of a soil and vinasse mixture
      during aerobic or anaerobic incubation.
AB  - Mineralization potentials are often used to classify organic wastes. These
      methods involve measuring CO(2) production during batch experiments, so
      variations in chemical compounds are not addressed. Moreover, the physicochemical
      conditions are not monitored during the reactions. The present study was designed
      to address these deficiencies. Incubations of a mixture of soil and waste
      (vinasse at 20% dry matter from a fermentation industry) were conducted in
      aerobic and anaerobic conditions, and liquid samples obtained by centrifugation
      were collected at 2h, 1d and 28 d. Dissolved organic carbon (DOC) patterns
      highlighted that: there was a "soil effect" which increased organic matter (OM)
      degradation in all conditions compared to vinasse incubated alone; and OM
      degradation was faster under aerobic conditions since 500 mgkg(-1) of C remained
      after aerobic incubation, as compared to 4000 mgkg(-1) at the end of the
      anaerobic incubation period. No changes were detected by Fourier transform
      infrared spectroscopy (FTIR) between 2h and 1d incubation. At 28 days incubation,
      the FTIR signal of the aerobic samples was deeply modified, thus confirming the
      high OM degradation. Under anaerobic conditions, the main polysaccharide
      contributions (nu(C-O)) disappeared at 1000 and 1200 cm(-1), as also confirmed by
      the (13)C NMR findings. Under aerobic incubation, a 50% decrease in the
      polysaccharide proportion was observed. Under anaerobic conditions, significant
      chemical modifications of the organic fraction were detected, namely formation of
      low molecular weight organic acids.

PMID- 19157831
TI  - Experimental study of behavior of endocrine-disrupting chemicals in leachate
      treatment process and evaluation of removal efficiency.
AB  - An experimental study of the behavior of endocrine-disrupting chemicals (EDCs) in
      leachate treatment processes (aeration, coagulation and sedimentation, activated
      carbon adsorption, and advanced oxidation) was conducted and removal efficiencies
      were evaluated. Among target EDCs, concentrations of BPA (1800 times), DBP (10
      times), BBP (40 times), and DEHP (30 times) in leachate are more than ten times
      higher than those in surface water. BPA, DBP, and BBP can be treated by aeration
      and DEHP, by advanced oxidation processes. BPA could not be effectively removed
      by coagulation and sedimentation because most of BPA partitioned in the
      supernatant. DEHP could hardly be treated by aeration. The removal ratios of DEHP
      were approximately 50-70% if the generated sediment was removed completely. The
      removal ratios of DEHP in leachate of 100 m(3)/d with 100 kg of activated carbon
      were 50-70%, assuming a complete mixing model. The concentration of DEHP was
      decreased to below one-tenth in 120 min by advanced oxidation processes.

PMID- 19157832
TI  - Anaerobic biodegradation of cellulosic material: batch experiments and modelling
      based on isotopic data and focusing on aceticlastic and non-aceticlastic
      methanogenesis.
AB  - Utilizing stable carbon isotope data to account for aceticlastic and non
      aceticlastic pathways of methane generation, a model was created to describe
      laboratory batch anaerobic decomposition of cellulosic materials (office paper
      and cardboard). The total organic and inorganic carbon concentrations, methane
      production volume, and methane and CO(2) partial pressure values were used for
      the model calibration and validation. According to the fluorescent in situ
      hybridization observations, three groups of methanogens including strictly
      hydrogenotrophic methanogens, strictly aceticlastic methanogens (Methanosaeta
      sp.) and Methanosarcina sp., consuming both acetate and H(2)/H(2)CO(3) as well as
      acetate-oxidizing syntrophs, were considered. It was shown that temporary
      inhibition of aceticlastic methanogens by non-ionized volatile fatty acids or
      acidic pH was responsible for two-step methane production from office paper at 35
      degrees C where during the first and second steps methane was generated mostly
      from H(2)/H(2)CO(3) and acetate, respectively. Water saturated and unsaturated
      cases were tested. According to the model, at the intermediate moisture (150%),
      much lower methane production occurred because of full-time inhibition of
      aceticlastic methanogens. At the lowest moisture, methane production was very low
      because most likely hydrolysis was seriously inhibited. Simulations showed that
      during cardboard and office paper biodegradation at 55 degrees C, non
      aceticlastic syntrophic oxidation by acetate-oxidizing syntrophs and
      hydrogenotrophic methanogens were the dominant methanogenic pathways.

PMID- 19157833
TI  - Effect of Phanerochaete chrysosporium inoculation during maturation of co
      composted agricultural wastes mixed with olive mill wastewater.
AB  - The co-composting of olive mill wastewater with a variety of agricultural wastes
      was investigated. To reduce the toxicity of the phenolic fraction and to improve
      the degree of maturity of the compost, inoculation with the white-rot fungus
      Phanerochaete chrysosporium was carried out during the maturation phase. The
      results showed that agricultural wastes that contain high levels of lignin
      related compounds, such as the residue from trimmings, improved the microbial
      activity and thus reduced the soluble phenols residue. The inoculation of P.
      chrysosporium during compost maturation reduced and modified the phenolic
      fraction, allowing a reduction in the time to reach compost maturity with the
      improvement in the germination index of 100% after 36 days in two of three trials
      performed.

PMID- 19157834
TI  - Sustainable management measures for healthcare waste in China.
AB  - This paper discusses actions aimed at sustainable management of healthcare wastes
      (HCW) in China, taking into account the current national situation in this field,
      as well as the requirements deriving from the Stockholm Convention on Persistent
      Organic Pollutants and the WHO recommendations. By the end of 2005, there were
      149 low-standard HCW disposal facilities in operation in China, distributed
      throughout different areas. According to the National Hazardous Waste and
      Healthcare Waste Disposal Facility Construction Plan, 331 modern, high-standard,
      centralized facilities will be built up in China in municipal level cities.
      Although incineration is still the main technical option for HCW disposal in
      China, it is expected that, especially for medium and small size facilities, non
      incineration technologies will develop quickly and will soon become the main
      technical option. The basic management needs - both from the point of view of
      pollution control and final disposal - have been defined, and a system of
      technical and environmental standards has been formulated and implemented;
      however, there are still some shortages. This is particularly true when
      considering the best available techniques and best environmental practices
      developed under the Stockholm Convention, with which the present technological
      and managing situations are not completely compliant. In this framework, the
      lifecycle (from generation to final disposal of wastes) of HCW and holistic
      approaches (technology verification, facilities operation, environmental
      supervision, environmental monitoring, training system, financial mechanism,
      etc.) towards HCW management are the most important criteria for the sustainable
      and reliable management of HCW in China.

PMID- 19157835
TI  - Life cycle impact assessment of various waste conversion technologies.
AB  - Advanced thermal treatment technologies utilizing pyrolysis or gasification, as
      well as a combined approach, are introduced as sustainable methods to treat
      wastes in Singapore. Eight different technologies are evaluated: pyrolysis
      gasification of MSW; pyrolysis of MSW; thermal cracking gasification of
      granulated MSW; combined pyrolysis, gasification and oxidation of MSW; steam
      gasification of wood; circulating fluidized bed (CFB) gasification of organic
      wastes; gasification of RDF; and the gasification of tyres. Life cycle assessment
      is carried out to determine the environmental impacts of the various waste
      conversion systems including global warming potential, acidification potential,
      terrestrial eutrophication and ozone photochemical formation. The normalization
      and weighting results, calculated according to Singapore national emission
      inventories, showed that the two highest impacts are from thermal cracking
      gasification of granulated MSW and the gasification of RDF; and the least are
      from the steam gasification of wood and the pyrolysis-gasification of MSW. A
      simplified life cycle cost comparison showed that the two most costs-effective
      waste conversion systems are the CFB gasification of organic waste and the
      combined pyrolysis, gasification and oxidation of MSW. The least favorable -
      highest environmental impact as well as highest costs - are the thermal cracking
      gasification of granulated MSW and the gasification of tyres.

PMID- 19157836
TI  - Abundance of (14)C in biomass fractions of wastes and solid recovered fuels.
AB  - In recent years thermal utilization of mixed wastes and solid recovered fuels has
      become of increasing importance in European waste management. Since wastes or
      solid recovered fuels are generally composed of fossil and biogenic materials,
      only part of the CO(2) emissions is accounted for in greenhouse gas inventories
      or emission trading schemes. A promising approach for determining this fraction
      is the so-called radiocarbon method. It is based on different ratios of the
      carbon isotopes (14)C and (12)C in fossil and biogenic fuels. Fossil fuels have
      zero radiocarbon, whereas biogenic materials are enriched in (14)C and reflect
      the (14)CO(2) abundance of the ambient atmosphere. Due to nuclear weapons tests
      in the past century, the radiocarbon content in the atmosphere has not been
      constant, which has resulted in a varying (14)C content of biogenic matter,
      depending on the period of growth. In the present paper (14)C contents of
      different biogenic waste fractions (e.g., kitchen waste, paper, wood), as well as
      mixtures of different wastes (household, bulky waste, and commercial waste), and
      solid recovered fuels are determined. The calculated (14)C content of the
      materials investigated ranges between 98 and 135pMC.

PMID- 19157837
TI  - Recovery of valuable materials from waste liquid crystal display panel.
AB  - Associated with the rapid development of the information and electronic industry,
      liquid crystal displays (LCDs) have been increasingly sold as displays. However,
      during the discarding at their end-of-life stage, significant environmental
      hazards, impacts on health and a loss of resources may occur, if the scraps are
      not managed in an appropriate way. In order to improve the efficiency of the
      recovery of valuable materials from waste LCDs panel in an environmentally sound
      manner, this study presents a combined recycling technology process on the basis
      of manual dismantling and chemical treatment of LCDs. Three key processes of this
      technology have been studied, including the separation of LCD polarizing film by
      thermal shock method the removal of liquid crystals between the glass substrates
      by the ultrasonic cleaning, and the recovery of indium metal from glass by
      dissolution. The results show that valuable materials (e.g. indium) and harmful
      substances (e.g. liquid crystals) could be efficiently recovered or separated
      through above-mentioned combined technology. The optimal conditions are: (1) the
      peak temperature of thermal shock to separate polarizing film, ranges from 230 to
      240 degrees C, where pyrolysis could be avoided; (2) the ultrasonic-assisted
      cleaning was most efficient at a frequency of 40 KHz (P = 40 W) and the exposure
      of the substrate to industrial detergents for 10 min; and (3) indium separation
      from glass in a mix of concentrated hydrochloric acid at 38% and nitric acid at
      69% (HCl:HNO(3):H(2)O = 45:5:50, volume ratio). The indium separation process was
      conducted with an exposure time of 30 min at a constant temperature of 60 degrees
      C.

PMID- 19157838
TI  - Medical waste management in China: a case study of Nanjing.
AB  - Medical waste management is of great importance due to its infectious and
      hazardous nature that can cause undesirable effects on humans and the
      environment. The objective of this study was to analyze and evaluate the present
      status of medical waste management in the light of medical waste control
      regulations in Nanjing. A comprehensive inspection survey was conducted for 15
      hospitals, 3 disposal companies and 200 patients. Field visits and a
      questionnaire survey method were implemented to collect information regarding
      different medical waste management aspects, including medical waste generation,
      segregation and collection, storage, training and education, transportation,
      disposal, and public awareness. The results indicated that the medical waste
      generation rate ranges from 0.5 to 0.8 kg/bed day with a weighted average of 0.68
      kg/bed day. The segregated collection of various types of medical waste has been
      conducted in 73% of the hospitals, but 20% of the hospitals still use unqualified
      staff for medical waste collection, and 93.3% of the hospitals have temporary
      storage areas. Additionally, 93.3% of the hospitals have provided training for
      staff; however, only 20% of the hospitals have ongoing training and education. It
      was found that the centralized disposal system has been constructed based on
      incineration technology, and the disposal cost of medical waste is about 580
      US$/ton. The results also suggested that there is not sufficient public
      understanding of medical waste management, and 77% of respondents think medical
      waste management is an important factor in selecting hospital services. The
      problematic areas of medical waste management in Nanjing are addressed by
      proposing some recommendations that will ensure that potential health and
      environmental risks of medical waste are minimized.

PMID- 19157839
TI  - Regulating the hydrolysis of organic wastes by micro-aeration and effluent
      recirculation.
AB  - In this study, the effects of micro-aeration and liquid recirculation on the
      hydrolysis of vegetable and flower wastes during two-phase solid-liquid anaerobic
      digestion were assessed. To accomplish this, we evaluated the hydrolysis of five
      batches of waste that were treated under the following conditions: anaerobic,
      insufficient micro-aeration (aeration for 5 min every 24 h), and sufficient micro
      aeration (aeration for 5 min every 12, 4 and 1h). Hydrolysis was found to depend
      on the level of micro-aeration. Specifically, insufficient micro-aeration led to
      unstable and decreased performance. Conversely, sufficient micro-aeration
      promoted the hydrolysis of easily biodegradable carbohydrates and proteins, but
      the microbial activity was later impaired by liquid recirculation using
      methanogenic effluent. The hydrolysis efficiency under anaerobic conditions was
      comparable to the efficiency observed under sufficient micro-aeration, while the
      cumulative TOC of the anaerobic batch was 1.4-2.4 times higher than that of the
      micro-aerated batches. In addition, liquid recirculation did not have a negative
      effect on the development of microbial activity under anaerobic conditions, which
      resulted in the lignocelluloses having a higher hydrolysis efficiency.

PMID- 19157840
TI  - Municipal solid waste management in Lahore City District, Pakistan.
AB  - This study deals with generation, composition, collection, transportation, and
      disposal, as well as the present cost of the waste management on the basis of 60%
      collection of the total waste and the cost of proposed improved system of
      management on the basis of 100% waste collection using the IWM-2 LCI model. A GIS
      map of Data Ganj Bakhsh Town (DGBT) of Lahore City District showing communal
      storage facilities is also provided. DGBT has a population of 1,624,169 living in
      232,024 dwellings. The total waste generated per year is 500,000 tons, or
      0.84/kg/cap/day. Presently 60% of the MSW is collected and disposed in open
      dumps, while 40% is not collected and lies along roadsides, streets railway
      lines, depressions, vacant plots, drains, storm drains and open sewers. In DGBT,
      129 containers of 5-m(3) capacity, 120 containers of 10-m(3) capacity and 380
      skips of 2.5-m(3) capacity are placed for waste collection. The overall
      collection and disposal cost of the MSW of DGBT is $3,177,900/yr, which is
      $10.29/ton. Modeling was conducted using the IWM-2 model for improved collection
      and disposal on the basis of 100% service, compared to the current 60% service.
      The modelled cost is $8.3/per ton, which is 20% less than the present cost, but
      the overall cost of 100% collection and disposal increases to $4,155,737/yr.

PMID- 19157841
TI  - Discrimination of specific and non-specific bindings by dielectrophoretic
      repulsion in on-chip magnetic bio-assays.
AB  - Affinity binding is the principle used in a large number of bio-assays. Aside
      from specific bindings, non-specific bindings usually deteriorate assays by
      giving false positive signals and restrict the detection limit. Currently, the
      assay specificity is mainly dependent on the effectiveness of a suitable surface
      chemistry. We report an approach to discriminate specific and non-specific
      bindings with dielectrophoretic (DEP) forces for on-chip magnetic bio-assays.
      Conjugated to the analytes, magnetic particles were used as the agents for DEP
      force generation. Due to a weaker binding strength, the non-specifically bound
      particles were removed while specific bindings remained intact. Analytical and
      finite element calculations were also performed to study all relevant forces.
      Furthermore, the removal of magnetic particles was also assessed by measuring the
      magnetic signal using magnetoresistive sensors. This technique can not only be
      used to improve the specificity of the on-chip bio-assays but also be developed
      as a tool of force spectroscopy for the study of bio-molecular binding physics.

PMID- 19157842
TI  - Microelectronic system for high-resolution mapping of extracellular electric
      fields applied to brain slices.
AB  - There is an enduring quest for technologies that provide - temporally and
      spatially - highly resolved information on electric neuronal or cardiac activity
      in functional tissues or cell cultures. Here, we present a planar high-density,
      low-noise microelectrode system realized in microelectronics technology that
      features 11,011 microelectrodes (3,150 electrodes per mm(2)), 126 of which can be
      arbitrarily selected and can, via a reconfigurable routing scheme, be connected
      to on-chip recording and stimulation circuits. This device enables long-term
      extracellular electrical-activity recordings at subcellular spatial resolution
      and microsecond temporal resolution to capture the entire dynamics of the
      cellular electrical signals. To illustrate the device performance, extracellular
      potentials of Purkinje cells (PCs) in acute slices of the cerebellum have been
      analyzed. A detailed and comprehensive picture of the distribution and dynamics
      of action potentials (APs) in the somatic and dendritic regions of a single cell
      was obtained from the recordings by applying spike sorting and spike-triggered
      averaging methods to the collected data. An analysis of the measured local
      current densities revealed a reproducible sink/source pattern within a single
      cell during an AP. The experimental data substantiated compartmental models and
      can be used to extend those models to better understand extracellular single-cell
      potential patterns and their contributions to the population activity. The
      presented devices can be conveniently applied to a broad variety of biological
      preparations, i.e., neural or cardiac tissues, slices, or cell cultures can be
      grown or placed directly atop of the chips for fundamental mechanistic or
      pharmacological studies.

PMID- 19157843
TI  - Development of an on-line SPR-digestion-nanoLC-MS/MS system for the
      quantification and identification of interferon-gamma in plasma.
AB  - An automated, on-line system for protein quantification and identification,
      employing Surface Plasmon Resonance (SPR), enzymatic protein digestion, nanoLC
      and tandem-MS (MS/MS), has been developed. For the experiments recombinant human
      interferon-gamma (rhIFN-gamma) in buffer or diluted bovine plasma was used as a
      model protein. Upon injecting 90muL of a 1mugmL(-1) solution of rhIFN-gamma in
      diluted plasma at a flow rate of 10muLmin(-1), 320fmol of protein was
      reproducibly bound to the sensor surface. After desorption of the isolated
      protein from the SPR surface using 10mM glycine pH 1.3, on-line digestion, nanoLC
      and MS/MS analysis, rhIFN-gamma could be identified on basis of peptide masses
      and MS/MS fragmentation data. A sequence recovery of 66% was found when a pepsin
      micro reactor was used. For a trypsin micro reactor the sequence recovery was
      50%. In the latter case, the desorbed protein solution was pH-tuned with a TRIS
      buffer for optimal enzyme activity. With the identified trypsin- and pepsin
      produced peptides and because parts of their amino acid sequences overlap, the
      protein sequence can be largely elucidated showing the potential for the analysis
      of unknown proteins. The SPR-digestion-nanoLC-MS/MS platform provides unattended
      analysis of a sample within 60min.

PMID- 19157844
TI  - Comparative study of SPR and ELISA methods based on analysis of CD166/ALCAM
      levels in cancer and control human sera.
AB  - Surface plasmon resonance (SPR), as a label free method for analysis of various
      analytes, has significantly advanced in recent years. However, assessment of the
      performance of SPR compared to label-based immunoassays such as the commonly used
      multiplexed enzyme-linked immunosorbent assay (ELISA) is limited, particularly
      for applications involving complex media. In this work, an optimized SPR assay
      was implemented and its performance compared with an ELISA assay for
      CD166/activated cell leukocyte adhesion molecule (ALCAM), as candidate pancreatic
      cancer marker, based on direct and amplified detection in buffer and in human
      serum samples from healthy individuals and subjects with cancer. ALCAM antibody
      was immobilized on the surface of a four-channel SPR sensor via physical
      adsorption onto charged amine-terminated alkanethiolates to mimic the ELISA plate
      surface. Excellent correlations between SPR and ELISA results were achieved in
      buffer and in human serum. SPR detected the target protein with a similar
      sensitivity to sandwich ELISA, with a detection limit below ng/mL. The detection
      time, sample consumption, throughput, signal referencing, and surface blocking
      and washing for detection in human serum were evaluated. It is demonstrated that
      SPR can distinguish between ALCAM levels in cancer and control sera using direct
      detection without the need for additional amplification steps.

PMID- 19157845
TI  - Design of a new cartridge for selective solid phase extraction using molecularly
      imprinted polymers: selective extraction of theophylline from human serum
      samples.
AB  - This paper describes design of a new cartridge for selective solid phase
      extraction (SPE) using molecularly imprinted polymers (MIPs). The apparatus which
      is termed solvent extraction-MISPE (SE-MISPE) cartridge, consisted of a modified
      conventional micro test tube and has been developed to perform simultaneous
      forward-extraction of analyte from aqueous sample solution to an organic phase
      and back-extraction to MIP solid phase. In order to evaluate the performance of
      the proposed method, extraction of theophylline (THP) from human serum sample was
      investigated. An appropriate amount of THP-imprinted polymer was placed in the
      bottom of the micro tube and an organic solvent pipetted onto it and left to
      swell the polymer completely. A polyethylene frit to secure MIP particles was
      positioned by two Teflon rings such that it was fixed below the level of the
      organic layer. Then, aqueous sample solution containing THP was layered over the
      organic phase and the lid was closed. After completion of extraction, the organic
      and aqueous phases were removed and the adsorbed analyte was desorbed using a
      polar organic solvent. In order to reach the highest recovery, the experimental
      parameters such as the type of organic solvent, pH and ionic strength of aqueous
      phase, organic to aqueous volume ratio, time of extraction, type and amount of
      desorbent solvent were optimized. Under the experimental conditions, a plot of
      HPLC peak areas vs. initial concentrations of THP in the concentration interval
      of 0.5-30 microg ml(-1) showed a good linearity (r=0.9974). The limit of
      detection (LOD) and limit of quantification (LOQ) based on three and ten times of
      the noise of HPLC profile were 0.09 and 0.3 microg ml(-1), respectively. The
      relative standard deviation (RSD) of the proposed method for the extraction and
      determination of 5 microg THP from 200 microl standard sample solution for 3
      replicate measurements was 3.5%. The results showed that by means of the proposed
      cartridge, THP could significantly separate from the other structurally related
      compounds such as theobromine (THB) and caffeine (CAF). The added THP could be
      quantitatively recovered (79-83%) from the serum samples by the proposed
      procedure, being thus a guarantee of the accuracy of the SE-MISPE procedure. In
      addition, the loss of capability of the SE-MISPE cartridge was not considerably
      observed after 10 times loading and elution cycles.

PMID- 19157846
TI  - A microfluidic detection system based upon a surface immobilized biobarcode
      assay.
AB  - The biobarcode assay (BCA) is capable of achieving low detection limits and high
      specificity for both protein and DNA targets. The realization of a BCA in a
      microfluidic format presents unique opportunities and challenges. In this work,
      we describe a modified form of the BCA called the surface immobilized biobarcode
      assay (SI-BCA). The SI-BCA employs microchannel walls functionalized with
      antibodies that bind with the intended targets. Compared with the conventional
      BCA, it reduces the system complexity and results in shortened process time,
      which is attributed to significantly reduced diffusion times in the micro-scale
      channels. Raw serum samples, without any pretreatment, were evaluated with this
      technique. Prostate specific antigen in the samples was detected at
      concentrations ranging from 40 pM to 40 fM. The detection limit of the assay
      using buffer samples is 10 fM. The entire assay, from sample injection to final
      data analysis was completed in 80 min.

PMID- 19157847
TI  - Investigations on copper-titanate intercalation materials for amperometric
      sensor.
AB  - Copper-based titanate intercalation electrode materials (referred as Cu-TO) were
      achieved by electrochemical reduction of the intercalated cupric ions that were
      ion exchanged on the layer structured titanate films by using n-propylamine as an
      exfoliating agent. The copper-based titanate intercalation electrode materials
      were characterized by X-ray diffraction (XRD), electrochemical techniques and
      inductive coupled plasma-atomic emission spectroscopy (ICP-AES). These copper
      based titanate materials were exploited to fabricate the enzymeless glucose
      sensors, and their assay performances to glucose were evaluated by conventional
      electrochemical techniques. Cyclic voltammetry (CV) and chronoamperometry (I-t)
      revealed a high sensitivity, fast response, excellent stability, and good
      reproducibility in the glucose determination at +0.55 V. Under optimal
      conditions, the electrocatalytic response of the sensor was proportional to the
      glucose concentration in the range of 2.5x10(-7) M to 8.0x10(-3) M with a
      detection limit of 5.0x10(-8) M (signal-to-noise=3). Moreover, the intercalated
      copper electrode materials exhibited high stability and improved selectivity for
      glucose compared with the more apparently accessible copper. This work also
      provides a simply controlled test-bed for electrochemical functionalization of
      layered titanate for sensor applications.

PMID- 19157848
TI  - Multiplexed plasmonic sensing based on small-dimension nanohole arrays and
      intensity interrogation.
AB  - We performed multiplexed sensing on nanohole array devices to simultaneously
      obtain information on molecular absorption, scattering, and refractive-index
      change, which were distinguished by using different array structures with
      distinct optical behavior. Up to 25 arrays were fabricated within a 65 microm x
      50 microm area to provide real-time information of the local surface environment.
      The performance of multiplexed sensing was examined by flowing NaCl, Coomassie
      blue, bovine serum albumin, and liposome solutions that exhibit different visible
      light absorption/scattering properties and different refractive indices.
      Experimental artifacts from light source fluctuation, sample injections, and
      light scattering induced by aggregates in solutions were detected by monitoring
      superwavelength holes or nanohole arrays with different periodicity and hole
      diameters.

PMID- 19157849
TI  - Copper UPD as non-specific adsorption barrier in electrochemical displacement
      immunosensors.
AB  - Non-specific adsorption events are responsible to a large extent for the lack of
      reliability and applicability of electrochemical immunosensors. In the particular
      case of displacement-based immunosensors, as an approach to achieve reagentless,
      labelless and easy to use immunosensors, the hindering effect of then non
      specific adsorption is amplified when the system presents a low affinity constant
      between biorecognition element and target. The application of Copper UPD as non
      specific adsorption barrier in combination with the use of self-assembled
      monolayers (SAM) to provide efficient binding of biomolecules to the immunosensor
      electrode surface is shown to be a very promising mechanism to construct protein
      resistant surfaces with no harming effects on the electrochemical transducing
      mechanism. The electrochemical immunodetection of TCA (2,4,6-Trichloroanisole)
      has been chosen as example for a real case study. A monoclonal antibody to detect
      the target TCA and an appropriate sub-optimum antigen were used. In addition to a
      rational strategy for displacement immunosensor development, the decrease of non
      specific adsorption phenomena by introducing Copper UPD is reported here. With
      such strategy an electrochemical displacement immunosensor with a limit of
      detection of 200ppb and response time of 10min is achieved.

PMID- 19157850
TI  - Cesarean section and primary pulmonary hypertension: the role of intravenous
      dexmedetomidine.
AB  - Primary pulmonary hypertension is a fatal disease that frequently becomes evident
      in pregnancy. The management of pregnant women with primary pulmonary
      hypertension poses a number of difficult problems, especially where regional
      anesthesia is considered to be contraindicated. A 30-year-old woman who developed
      primary pulmonary hypertension at 23 weeks of pregnancy was transferred to our
      hospital. Systolic pulmonary artery pressure and plasma brain natriuretic peptide
      levels were markedly elevated. Nitric oxide inhalation and prostacyclin prevented
      the progression of cardiac failure and reduced both plasma brain natriuretic
      peptide and pulmonary artery pressure. Cesarean section was performed at 32 weeks
      under general anesthesia. A combination of nitric oxide, prostacyclin,
      nitroglycerin, and dobutamine were administered during surgery. Intravenous
      dexmedetomidine was specifically used during emergence and recovery from
      anesthesia. This provided effective pain relief and hemodynamic stability.
      Throughout the clinical course, brain natriuretic peptide levels was monitored
      and used as an indicator of cardiac failure.

PMID- 19157851
TI  - The effects of meperidine and epidural analgesia in labor on maternal heart rate
      variability.
AB  - BACKGROUND: Epidural and parenteral opioid analgesia are two common methods of
      pain relief in labor that may influence the autonomic nervous system. However,
      these effects on laboring women have not yet been adequately studied. The aim of
      our study was to assess the effects of these two methods of analgesia on
      autonomic nervous system modulation of maternal heart rate variability in
      laboring women. METHODS: A prospective observational study was conducted on 64
      laboring women; 33 received epidural analgesia with bupivacaine and fentanyl and
      31 intravenous meperidine and promethazine. Power spectral analysis and nonlinear
      methods were applied to digitized electrocardiograms performed before and after
      administration of analgesia, to assess maternal heart rate variability and
      autonomic equilibrium. RESULTS: Maternal heart rate significantly increased in
      women who received meperidine compared to those who had epidural analgesia. There
      was a significant increase in the low-frequency to high-frequency ratio (3.7+/
      3.9 vs. 1.8+/-1.6, P<0.05), and a significant decrease of high-frequency spectral
      power in women who had meperidine compared to those who received epidural
      analgesia (163+/-91 vs. 98+/-100 ms(2)/Hz, P<0.05). CONCLUSIONS: Meperidine
      caused an autonomic nervous system shift towards sympathetic activation with
      abolition of respiratory sinus arrhythmia high-frequency spectral band.
      Conversely epidural analgesia had no significant effect on autonomic nervous
      system control of heart rate.

PMID- 19157852
TI  - Folding and stability of globular proteins and implications for function.
AB  - The description of protein folding pathways and the principles that govern them
      has proven to be one of the most difficult problems to be solved in structural
      biology. But the combination of experiments and simulations has now provided a
      clearer picture of the chemistry involved. Once folded, however, proteins remain
      dynamic systems making possible both small-scale and large-scale structural
      and/or dynamical changes upon binding or releasing of ligands and during
      catalysis. In this review we focus on recent advances in the field of protein
      folding and discuss possible links between folding, stability, and binding
      dynamics.

PMID- 19157853
TI  - Mechanochemistry of receptor-ligand bonds.
AB  - When cell receptors bind to immobilized ligands, the resulting bond can be
      subjected to tensile mechanical force. This might be expected to shorten bond
      lifetimes. However, cells from bacteria to blood cells express receptors that are
      activated by tensile force to form longer-lived bonds, referred to as catch
      bonds. The process of catch bond activation involves non-equilibrium processes
      that are poorly probed by experimental and computational structural methods
      alike. However, I argue here that the preponderance of data indicates that force
      acts on an interdomain region which regulates the conformation of a distal ligand
      binding site, in a process closely related to mechanochemistry and allosteric
      regulation.

PMID- 19157854
TI  - Folding scene investigation: membrane proteins.
AB  - Investigations into protein folding have concentrated on experimentally tractable
      proteins with the result that membrane protein folding remains unsolved. New
      evidence is providing insight into the nature of the interactions stabilising the
      folded state of alpha-helical membrane proteins as well as giving hints on the
      character of the folding transition state. These developments show that classical
      methods used for water-soluble proteins can be successfully adapted for membrane
      proteins. The advances, coupled with increasing numbers of solved crystal
      structures, augur well for future research into the mechanisms of membrane
      protein folding.

PMID- 19157855
TI  - Linking folding and binding.
AB  - Many cellular proteins are intrinsically disordered and undergo folding, in whole
      or in part, upon binding to their physiological targets. The past few years have
      seen an exponential increase in papers describing characterization of
      intrinsically disordered proteins, both free and bound to targets. Although NMR
      spectroscopy remains the favored tool, a number of new biophysical techniques are
      proving exceptionally useful in defining the limits of the conformational
      ensembles. Advances have been made in prediction of the recognition elements in
      disordered proteins, in elucidating the kinetics and mechanism of the coupled
      folding and binding process, and in understanding the role of post-translational
      modifications in tuning the biological response. Here we review these and other
      recent advances that are providing new insights into the conformational
      propensities and interactions of intrinsically disordered proteins and are
      beginning to reveal general principles underlying their biological functions.

PMID- 19157856
TI  - Prion protein misfolding and disease.
AB  - Transmissible spongiform encephalopathies (TSEs or prion diseases) are a rare
      group of invariably fatal neurodegenerative disorders that affect humans and
      other mammals. TSEs are protein misfolding diseases that involve the accumulation
      of an abnormally aggregated form of the normal host prion protein (PrP). They are
      unique among protein misfolding disorders in that they are transmissible and have
      different strains of infectious agents that are associated with unique phenotypes
      in vivo. A wealth of biological and biophysical evidence now suggests that the
      molecular basis for prion diseases may be encoded by protein conformation. The
      purpose of this review is to provide an overview of the existing structural
      information for PrP within the context of what is known about the biology of
      prion disease.

PMID- 19157857
TI  - Quality control in the surgical management of ovarian cancer patients.

PMID- 19157858
TI  - Applicability of staging systems for patients with hepatocellular carcinoma is
      dependent on treatment method--analysis of 2010 Taiwanese patients.
AB  - The aim of this study was to compare six prognostic staging systems (Okuda stage,
      TNM stage, CLIP score, BCLC stage, JIS score and Tokyo score) in predicting
      survival in patients with hepatocellular carcinoma (HCC). A total of 2010
      Taiwanese HCC patients were included. Demographic, laboratory and tumour
      characteristics were determined at diagnosis. Predictors of survival included
      serum levels of albumin, total bilirubin, alkaline phosphatase, alpha
      fetoprotein, ascites, tumour size and portal vein invasion. The Tokyo score was
      the most informative one for predicting the survival of HCC patients as a whole,
      receiving surgical resection, or receiving transarterial chemoembolisation. CLIP
      score was the best fit system for HCC patients receiving chemotherapy or
      supportive care. Each staging system showed a significant difference in
      predicting the probability of survival across different stages. The applicability
      of staging systems for patients with HCC was dependent on treatment methods.

PMID- 19157859
TI  - Glutathione S-transferase P1 gene polymorphism associated with gastric cancer
      among Caucasians.
AB  - Studies investigating the association between glutathione S-transferase P1
      (GSTP1) codon 105 polymorphism and gastric cancer risk report conflicting
      results. The objective of this study was to quantitatively summarise the evidence
      for such a relationship. Two investigators independently searched the Medline and
      Embase databases. This meta-analysis included 10 case-control studies, which
      included 1161 gastric cancer cases and 2847 controls. The combined results based
      on all studies showed that there was no significant difference in genotype
      distribution [AA odds ratio (OR)=1.14, 95% confidence interval (CI)=0.91, 1.44;
      AG (OR=0.82, 95% CI=0.66, 1.03); GG (OR=1.11, 95% CI=0.55, 2.24)] between gastric
      cancer and non-cancer patients. When stratifying for race, results were similar
      except that patients with gastric cancer had a significantly higher frequency of
      AA (OR=1.53, 95% CI=1.14, 2.06) and lower frequency of AG (OR=0.70, 95% CI=0.55,
      0.89) than non-cancer patients among Caucasians. When stratifying by the location
      and Lauren's classification of gastric cancer, we observed no statistically
      significant differences in genotype distribution. This meta-analysis suggests
      that the GSTP1 codon 105 polymorphism may be associated with gastric cancer among
      Caucasians.

PMID- 19157860
TI  - Tumoural expression and circulating level of VEGFR-3 (Flt-4) in metastatic
      melanoma patients: correlation with clinical parameters and outcome.
AB  - PURPOSE: The presence of metastases in regional lymph nodes is a strong indicator
      of poor patient survival in many types of cancer. It has recently been shown that
      vascular endothelial growth factor-C (VEGF-C), and its receptor VEGFR-3, may play
      a pivotal role in the promotion of metastasis to regional lymph nodes. This study
      was designed to detect and evaluate whether the expression of VEGFR-3 or its
      soluble form plays a role in metastatic malignant melanoma and to determine the
      relationship with clinicopathological parameters and patients outcome.
      EXPERIMENTAL DESIGN: VEGFR-3 expression on melanoma tumour was evaluated by
      immunohistochemical study. Using a sensitive enzyme-linked immunosorbent assay,
      sVEGFR-3 was measured in sera of 60 metastatic melanoma patients in comparison
      with 30 healthy controls. RESULTS: Immunohistochemical study demonstrated a high
      expression of VEGFR-3 in melanoma cells. Median level of pre-treatment sVEGFR-3
      was significantly higher (p=0.00001) in melanoma patients as compared to healthy
      donors. No association was noted between VEGFR-3 in situ or in sera and gender,
      age or LDH level. Median serum VEGFR-3 levels were significantly higher in
      patients with high tumour burden as compared to those with low tumour burden
      (p=0.013) as well as in non-responding patients (n=33) as compared to responding
      ones (n=27). Finally, low level of VEGFR-3 was also related positively to disease
      free survival (X(2)=3.85, p=0.022). CONCLUSION: These results suggest that the
      expression and high pre-treatment sVEGFR-3 level are significantly correlated to
      poorer prognosis, and may be promising targets for new therapeutic strategies in
      melanoma disease.

PMID- 19157861
TI  - EORTC-GU group expert opinion on metastatic renal cell cancer.
AB  - There is no consensus on the detailed surveillance of renal cell cancer (RCC)
      patients after radical resection of the kidney. Where relapse is unlikely, one
      reasonable option would be to confine investigations to chest X-ray and abdominal
      ultrasound -- carried out at 3-month intervals during the first year, but less
      frequently thereafter. These investigations could be supplemented by annual
      computerised tomography (CT) of the chest and abdomen. Where risk is intermediate
      or high, more frequent CT should be undertaken, taking into account the risks of
      repeated radiation exposure. Since the emergence of new and more effective
      treatments for metastatic disease, follow-up has tended to become more
      challenging not only with respect to disease assessment but also for evaluation
      of toxicity [Level 5]. The diagnostic work-up in metastatic RCC should include a
      history, physical examination and comprehensive blood screen. In addition,
      patients to be treated with targeted agents should have a thyroid function test.
      In patients with a relevant clinical history or who are otherwise at risk,
      cardiac function should be assessed, and this is also advisable in asymptomatic
      patients [Level 2b]. Nephrectomy is an important component of the multimodality
      treatment of mRCC. This procedure induces spontaneous regression of metastases in
      a small number of patients [Level 4]. More generally, it improves the survival of
      patients who subsequently receive immunotherapy [Level 1]. However, it is not yet
      known whether this benefit is also seen in patients treated with targeted agents
      [Level 2b]. Certain patients with metastases (even at multiple sites) have
      lesions that are resectable. Surgery is potentially curative in these cases and
      can be undertaken prior to use of cytokines or targeted agents [Level 2b].
      Vaccine-based therapies may have potential, particularly when disease burden is
      low [Level 4]. The outcome of ongoing trials is awaited. Metastatic RCC responds,
      albeit at a low rate, to cytokines. These agents may be helpful for a subgroup of
      patients. However, for the great majority, and certainly for those with
      intermediate- or poor-risk disease, cytokines confer no benefit [Level 1b].
      Choice of initial medical management in patients with metastatic clear-cell RCC
      should be guided by the pivotal, randomised studies. On the evidence available,
      the first-line therapy in patients with good- or intermediate-risk mRCC should be
      either sunitinib [Level 1b] or bevacizumab plus interferon [Level 1a]. In
      patients ineligible for sunitinib or bevacizumab plus interferon, sorafenib is an
      option, as is high-dose interleukin 2 if performance status is sufficiently good
      [Level 2b]. In patients with poor prognosis (as defined in the pivotal trial),
      temsirolimus is recommended [Level 1b]. In this group, sunitinib could be an
      alternative [Level 2b]. The role of targeted agents in the treatment of patients
      with RCC of non-clear-cell histologies remains to be established. In cytokine
      refractory patients, sorafenib is recommended [Level 1b]. Everolimus is the agent
      of choice when patients have progressed on a tyrosine kinase inhibitor [Level
      1b].

PMID- 19157862
TI  - Is there a place for N.O.T.E.S. in the diagnosis and treatment of neoplastic
      lesions of the pancreas?
AB  - Natural orifice transluminal endoscopic surgery (NOTES) is the latest minimally
      invasive technique in the surgical armamentarium. Indeed it is stoking
      controversy already among both practitioners and patients, challenging
      established surgical, ethical and even moral principles. One organ which has been
      at the forefront of minimally invasive intervention is the pancreas. This review
      looks at the basis for evolving NOTES capabilities in the diagnosis and treatment
      of pancreatic diseases, with particular reference to neoplastic lesions and their
      complications. A summary of recent advancements in gastro-intestinal endoscopy
      and laparoscopic surgery as applied to the pancreas is presented. The possible
      role and feasibility of NOTES are outlined against this background.

PMID- 19157863
TI  - Swine manure fermentation for hydrogen production.
AB  - Biohydrogen fermentation using liquid swine manure as substrate supplemented with
      glucose was investigated in this project. Experiments were conducted using a semi
      continuously-fed fermenter (8L in total volume and 4 L in working volume) with
      varying pHs from 4.7 through 5.9 under controlled temperature (35+/-1 degrees C).
      The hydraulic retention time (HRT) tested include 16, 20, and 24h; however, in
      two pH conditions (5.0 and 5.3), an additional HRT of 12h was also tried. The
      experimental design combining HRT and pH provided insight on the fermenter
      performance in terms of hydrogen generation. The results indicated that both HRT
      and pH had profound influences on fermentative hydrogen productivity. A rising
      HRT would lead to greater variation in hydrogen concentration in the offgas and
      the best HRT was found to be 16 h for the fermenter in this study. The best pH
      value in correspondence to the highest hydrogen generation was revealed to be 5.0
      among all the pHs studied. There was no obvious inhibition on hydrogen production
      by methanogenesis when methane content in the offgas was lower than 2%.
      Otherwise, an inverse linear relationship between hydrogen and methane content
      was observed with a correlation coefficient of 0.9699. Therefore, to increase
      hydrogen content in the offgas, methane production has to be limited to below 2%.

PMID- 19157864
TI  - Enhanced decolorization and biodegradation of textile azo dye Scarlet R by using
      developed microbial consortium-GR.
AB  - A developed consortium-GR, consisting of Proteus vulgaris NCIM-2027 (PV) and
      Micrococcus glutamicus NCIM-2168 (MG), completely decolorized an azo dye Scarlet
      R under static anoxic condition with an average decolorization rate of 16,666
      microg h(-1); which is much faster than that of the pure cultures (PV, 3571
      microg h(-1); MG, 2500 microg h(-1)). Consortium-GR gave best decolorization
      performance with nearly complete mineralization of Scarlet R (over 90% TOC and
      COD reduction) within 3h, much shorter relative to the individual strains.
      Induction in the riboflavin reductase and NADH-DCIP reductase was observed in the
      consortium, suggesting the involvement of these enzymes during the fast
      decolorization process. The FTIR and GC-MS analysis showed that 1,4
      benzenediamine was formed during decolorization/degradation of Scarlet R by
      consortium-GR. Phytotoxicity studies revealed no toxicity of the biodegraded
      products of Scarlet R by consortium-GR. In addition, consortium-GR applied for
      mixture of industrial dyes showed 88% decolorization under static condition with
      significant reduction in TOC (62%) and COD (68%) within 72 h, suggesting
      potential application of this microbial consortium in bioremediation of dye
      containing wastewater.

PMID- 19157865
TI  - Simple models for the release kinetics of dissolved organic carbon from woody
      filtration media.
AB  - The mechanisms and kinetics of dissolved organic carbon (DOC) release from woody
      materials (pine, hardwood and compost) under non-equilibrium leaching conditions
      was examined through batch and column tests. Mechanistically based kinetic models
      (first and second order) had a low predictive power for DOC release compared to
      those based solely on regression (Elovitch, power law). The DOC release data
      showed a bi-phasic response, with an early period of rapid release (<24h)
      controlled by film diffusion followed by a slower rate controlled by intra
      particle diffusion. After flow interruption, DOC release was primarily controlled
      by intra-particle diffusion; however, the specific rate parameters generally
      varied with each flow cycle and between different wood types.

PMID- 19157866
TI  - Biodegradation of trichloroethylene (TCE) by methanotrophic community.
AB  - Laboratory incubation experiments were carried out to assess the potential of
      methanotrophic culture for degrading TCE. Measurements of the growth rate and TCE
      degradation showed that the methanotrophs not only grew in presence of TCE but
      also degraded TCE. The rate of TCE degradation was found to be 0.19 ppm h(-1).
      The reverse transcriptase-PCR test was conducted to quantify expression of pmoA
      and mmoX genes. RT-PCR revealed expression of pmoA gene only. This observation
      provides evidence that the pmoA gene was functionally active for pMMO enzyme
      during the study. The diversity of the methanotrophs involved in TCE degradation
      was assessed by PCR amplification, cloning, restriction fragment length
      polymorphism and phylogenetic analysis of pmoA genes. Results suggested the
      occurrence of nine different phylotypes belonging to Type II methanotrophs in the
      enriched cultures. Out of the nine, five clustered with, genera Methylocystis and
      rest got clustered in to a separate group.

PMID- 19157867
TI  - Comparison of horizontal and vertical constructed wetland systems for landfill
      leachate treatment.
AB  - The main purpose of this study was to treat organic pollution, ammonia and heavy
      metals present in landfill leachate by the use of constructed wetland systems and
      to quantify the effect of feeding mode. The effect of different bedding material
      (gravel and zeolite surface) was also investigated. A pilot-scale study was
      conducted on subsurface flow constructed wetland systems operated in vertical and
      horizontal mode. Two vertical systems differed from each other with their bedding
      material. The systems were planted with cattail (Typha latifolia) and operated
      identically at a flow rate of 10 l/day and hydraulic retention times of 11.8 and
      12.5 day in vertical 1, vertical 2 and horizontal systems, respectively.
      Concentration based average removal efficiencies for VF1, VF2 and HF were NH(4)
      N, 62.3%, 48.9% and 38.3%; COD, 27.3%, 30.6% and 35.7%; PO(4)-P, 52.6%, 51.9% and
      46.7%; Fe(III), 21%, 40% and 17%, respectively. Better NH(4)-N removal
      performance was observed in the vertical system with zeolite layer than that of
      the vertical 2 and horizontal system. In contrast, horizontal system was more
      effective in COD removal.

PMID- 19157868
TI  - Utilisation of manure composts by high-value crops: safety and environmental
      challenges.
AB  - The intensification in livestock production has increased the need of efficient
      treatments of waste streams especially to preserve as much as possible, the
      nutrients into the soil-plant system. Composting is a cheap, efficient and
      sustainable treatment for solid wastes that is always included in any manure
      treatment scenario. In this paper, an overview about the environmental and safety
      challenges of composting of manures is made considering the compost quality
      requirements established by the main demanding sectors. Co-composting and
      additive strategies are presented as feasible options for the improvement of
      compost quality. For quality evaluation of manure compost, the use of both
      classical and innovative instrumental techniques could increase our knowledge
      about added properties in compost, especially those related to organic matter
      stability.

PMID- 19157869
TI  - Electricity production by an overflow-type wetted-wall microbial fuel cell.
AB  - An overflow-type wetted-wall MFC (WWMFC) was developed to generate a stable
      voltage from acetate-based substrates. The maximum power density of 18.21 W/m(3)
      was obtained. The power generation showed a saturation-type relationship as a
      function of initial COD, with a maximum power density (P(max)) of 18.82 W/m(3)
      and a saturation constant (K(s)) of 227.4 mg/l. Forced air flowing through the
      cathode chamber had a negligible effect on power generation. Influent flow rate
      could greatly affect the power generation. The maximum power density was
      increased by 72.8% when the influent flow rate increased from 5 to 30 ml/min. In
      addition, increasing ionic strength did not affect the power density and internal
      resistance. Oxygen could be restrained to diffuse into the anode chamber
      effectively in the overflow-type WWMFC. And the overflow-type WWMFC could be
      scaled up conveniently in practical application.

PMID- 19157870
TI  - Novel minor lipase from Rhizopus chinensis during solid-state fermentation:
      biochemical characterization and its esterification potential for ester
      synthesis.
AB  - Rhizopus chinensis produces two lipases that catalyze ester synthesis when
      cultured under solid-state fermentation. The Lip2 was purified to homogeneity by
      ammonium sulphate precipitation, hydrophobic interaction chromatography and gel
      filtration chromatography. It has an apparent molecular weight of 33 kDa
      estimated from SDS-PAGE and 32 kDa calculated from analytical gel permeation,
      with synthetic activity and purification fold of 96.8 U/mg and 138.3,
      respectively. Maximum hydrolytic activity was obtained at pH 8.0-8.5 and 40
      degrees C using pNPP as substrate. Slight activation of the enzyme was observed
      when Mn(2+) is present. The enzyme was most active on p-nitrophenyl laurate
      (C12). The purified lipase exhibited maximum synthetic activity at pH memory of
      6.0 and 30 degrees C. Most of ethyl esters synthesized by lyophilized enzyme
      achieved good yields (>90%), and caprylic acid served as the best acyl donor. The
      enzyme presented a particular affinity for ethanol, n-propanol and n-hexanol,
      with conversion of 92%, 93% and 92%, respectively, after 20 h incubation.

PMID- 19157871
TI  - Steam explosion lignins; their extraction, structure and potential as feedstock
      for biodiesel and chemicals.
AB  - In the present study, a steam explosion wood pre-treatment process, optimized
      earlier with respect to ethanol production, has been applied to both softwoods
      (Picea abies and Pinus sylvestris) and hardwoods (Betula verrucosa and Populus
      tremula). The alkaline extractable lignins have then been isolated to investigate
      lignin separation efficiency and lignin structure and to evaluate their potential
      for producing value-added products, such as biodiesel components or chemicals, in
      terms of the purity, molecular size, functional groups, beta-O-4' inter-unit
      linkage content, and degradability in a subsequent processing treatment. The
      mechanism of lignin modification and possible improvements to the steam explosion
      pre-treatment process are discussed.

PMID- 19157872
TI  - High-throughput screening for ionic liquids dissolving (ligno-)cellulose.
AB  - The recalcitrance of lignocellulosic biomass poses a major challenge for its
      sustainable and cost-effective utilization. Therefore, an efficient pretreatment
      is decisive for processes based on lignocellulose. A green and energy-efficient
      pretreatment could be the dissolution of lignocellulose in ionic liquids. Several
      ionic liquids were identified earlier which are capable to dissolve (ligno
      )cellulose. However, due to their multitude and high costs, a high-throughput
      screening on small scale is essential for the determination of the most efficient
      ionic liquid. In this contribution two high-throughput systems are presented
      based on extinction or scattered light measurements. Quasi-continuous dissolution
      profiles allow a direct comparison of up to 96 ionic liquids per experiment in
      terms of their dissolution kinetics. The screening results indicate that among
      the ionic liquids tested EMIM Ac is the most efficient for dissolving cellulose.
      Moreover, it was observed that AMIM Cl is the most effective ionic liquid for
      dissolving wood chips.

PMID- 19157873
TI  - A rapid method for generation of selective Sox-based chemosensors of Ser/Thr
      kinases using combinatorial peptide libraries.
AB  - A novel screening method to identify selective Sox-based fluorescent probes for
      Ser/Thr kinases has been developed. Peptide libraries were exposed to a kinase of
      interest and the products of the timed reaction were analyzed by MALDI-TOF. To
      demonstrate the potential of this methodology, a selective substrate for Aurora A
      kinase was identified that showed a 7-fold improvement in catalytic efficiency
      over the best substrate described to date in the literature.

PMID- 19157874
TI  - Interfamilial phenotypic heterogeneity in SMARD1.
AB  - Spinal muscular atrophy with respiratory distress (SMARD1: mu-binding protein 2
      gene mutation) is characterised by low birth weight, progressive distal limb
      weakness, diaphragmatic paralysis and subsequent respiratory failure manifesting
      before 13 months of age. Our case report illustrates marked phenotype variability
      in two siblings with an identical genetic mutation of SMARD1, one of whom died of
      fulminant respiratory failure aged 6 months, whereas the other shows limb
      weakness but, only mild sleep hypoventilation aged 12 years. This suggests other
      compensatory mechanisms may play a role in modifying SMARD1; broadening our
      perception of phenotype. Therefore, SMARD1 phenotype should be considered in
      cases of atypical spinal muscular atrophy even in the absence of overt
      diaphragmatic weakness.

PMID- 19157875
TI  - Myopathic form of phosphoglycerate kinase (PGK) deficiency: a new case and
      pathogenic considerations.
AB  - We describe an 18-year-old man with muscle cramps and recurrent exertional
      myoglobinuria, without hemolytic anemia or brain dysfunction. Phosphoglycerate
      kinase (PGK) deficiency was documented in muscle and erythrocytes and molecular
      analysis of the PGK1 gene identified a novel mutation, T378P. This is the ninth
      case presenting with isolated myopathy, whereas most other patients show
      hereditary non-spherocytic hemolytic anemia alone or associated with brain
      dysfunction, and a few patients have myopathy plus brain involvement. Although
      the diverse tissue involvement in PGK deficiency remains unclear, all mutations
      in myopathic patients tend to cluster in the C terminal domain, adjacent to the
      substrate-binding pocket. This may lead to a failure in the closure of the N
      terminal and C terminal domains and loss of stability due to lack of inter-domain
      communication during the catalytic process.

PMID- 19157876
TI  - Analysis of RhoC expression and lymphovascular emboli in inflammatory vs non
      inflammatory breast cancers in Egyptian patients.
AB  - Understanding the molecular factors that distinguish inflammatory breast cancer
      (IBC) from non-IBC is important for IBC diagnosis. We reviewed the records of 48
      IBC patients and 64 non-IBC patients from Egypt. We determined RhoC expression
      and tumor emboli and their relationship to demographic and reproductive
      characteristics. Compared with non-IBC patients, IBC patients had significantly
      lower parity (P=0.018) and fewer palpable tumors (P<0.0001). IBC tumors showed
      RhoC overexpression more frequently than non-IBC tumors (87% vs. 17%,
      respectively) (P<0.0001). Tumor emboli were significantly more frequent in IBC
      tumors than non-IBC tumors (Mean+/- SD: 14.1+/-14.0 vs. 7.0+/-12.9, respectively)
      (P<0.0001). This study illustrates that RhoC overexpression and tumor emboli are
      more frequent in tumors of IBC relative to non-IBC from Egypt. Future studies
      should focus on relating epidemiologic factors to molecular features of IBC in
      this population.

PMID- 19157877
TI  - Directional effects of biofeedback on trunk sway during gait tasks in healthy
      young subjects.
AB  - Biofeedback of trunk sway is a possible remedy for patients with balance
      disorders. Because these patients have a tendency to fall more in one direction,
      we investigated whether biofeedback has a directional effect on trunk sway during
      gait. Forty healthy young participants (mean age 23.1 years) performed 10 gait
      tasks with and without biofeedback. Combined vibrotactile, auditory and visual
      feedback on trunk sway in either the lateral or anterior-posterior (AP) direction
      was provided by a head-mounted actuator system. Trunk roll and pitch angles,
      calculated from trunk angular velocities measured with gyroscopes, were used to
      drive the feedback. A reduction in sway velocities occurred across all tasks
      regardless of feedback direction. Reductions in sway angles depended on the task.
      Generally, reductions were greater in pitch. For walking up and down stairs, or
      over barriers, pitch angle reductions were greater with AP than lateral feedback.
      For tandem and normal walking, reductions were similar in pitch and roll angles
      for both feedback directions. For walking while rotating or pitching the head or
      with eyes closed, only pitch angle was reduced for both feedback directions.
      These results indicate that the central nervous system is able to incorporate
      biofeedback of trunk sway from either the AP or lateral direction to achieve a
      reduction in both pitch and roll sway. Greater reductions in pitch suggest a
      greater ability to use this direction of trunk sway biofeedback during gait.

PMID- 19157878
TI  - Differences in plantar loading between flat and normal feet during different
      athletic tasks.
AB  - The purpose of this study was to determine if foot type (flat or normal) resulted
      in loading differences during four sport-specific tasks (cross-cut, side-cut,
      shuttle run, and landing from a simulated lay-up). Twenty-two healthy subjects
      (12 normal feet and 10 flat feet) completed five trials in each condition, while
      in-shoe pressure data was collected at 50 Hz. Contact area, maximum force, and
      the force time integral were analyzed under the entire foot and in eight-foot
      regions. Foot type was determined by examining navicular height, arch angle,
      rearfoot angle, and a clinical score. A series of independent sample t-tests were
      used to determine statistical differences (alpha<0.05). During the cross-cut,
      flat feet demonstrated an increase in medial midfoot contact area. During the
      side-cut, flat feet demonstrated an increase in contact area, force time integral
      and maximum force in both the medial and lateral midfoot. During the shuttle run,
      flat feet demonstrated an increase in force time integral in the lateral midfoot
      and increases in maximum force in both the medial and lateral midfoot. During the
      landing task, flat feet demonstrated an increase in maximum force in the medial
      midfoot. However, flat feet demonstrate a decrease in middle forefoot maximum
      force. All results were statistically significant (p<0.05). Therefore,
      individuals with a normal foot could be at a lower risk for medial and lateral
      midfoot injuries such as metatarsal stress fractures, indicating that foot type
      should be assessed when determining an individual's risk for metatarsal stress
      fractures.

PMID- 19157879
TI  - Pyoderma gangraenosum as a complication to knee arthroscopy.
AB  - Pyoderma gangraenosum (PG) is a rare immunologic ulcerative disease, which
      sometimes develop as a complication to surgery. PG is often misdiagnosed as an
      infected wound, but treatment is completely different. We report a case of PG as
      a complication to arthroscopic partial meniscectomy that resulted in arthrodesis
      of the knee. We discuss the differential diagnosis and treatment options.

PMID- 19157880
TI  - Synthesis of oligodeoxynucleotides incorporating 2-N-carbamoylguanine and
      evaluation of the hybridization properties.
AB  - Previously, we reported 2-N-carbamoylguanine (cmG) as a guanine analog. We
      further studied the synthetic protocol and hybridization properties of
      oligodeoxynucleotides (ODNs) incorporating cmG. These ODNs were synthesized using
      the phosphoramidite of cmG without protection of the 6-O position. However, the
      isolated products were contaminated with deacylated products having guanine in
      place of cmG. The detailed analysis of the synthetic process suggested that the
      deacylation resulted from the reaction of the carbamoyl moiety with capping
      reagents. Protection of the 6-O position suppressed the side reaction. The
      thermal stability of the DNA duplexes incorporating cmG was analyzed. An analysis
      of T(m) values revealed that the base discrimination ability of cmG was
      comparable to or higher than that of the canonical guanine depending on the
      flanking bases.

PMID- 19157881
TI  - Synthesis and cyclooxygenase inhibition of various (aryl-1,2,3-triazole-1-yl)
      methanesulfonylphenyl derivatives.
AB  - A series of 1,4- and 1,5-diaryl substituted 1,2,3-triazoles was synthesized by
      either Cu(I)-catalyzed or Ru(II)-catalyzed 1,3-dipolar cycloaddition reactions
      between 1-azido-4-methane-sulfonylbenzene 9 and a panel of various para
      substituted phenyl acetylenes (4-H, 4-Me, 4-OMe, 4-NMe(2), 4-Cl, 4-F). All
      compounds were used in in vitro cyclooxygenase (COX) assays to determine the
      combined electronic and steric effects upon COX-1 and COX-2 inhibitory potency
      and selectivity. Structure-activity relationship studies showed that compounds
      having a vicinal diaryl substitution pattern showed more potent COX-2 inhibition
      (IC(50)=0.03-0.36 microM) compared to their corresponding 1,3-diaryl-substituted
      counterparts (IC(50)=0.15 to >10.0 microM). In both series, compounds possessing
      an electron-withdrawing group (Cl and F) at the para-position of one of the aryl
      rings displayed higher COX-2 inhibition potency and selectivity as determined for
      compounds containing electron-donating groups (Me, OMe, NMe(2)). The obtained
      data show, that the central carbocyclic or heterocyclic ring system as found in
      many COX-2 inhibitors can be replaced by a central 1,2,3-triazole unit without
      losing COX-2 inhibition potency and selectivity. The high COX-2 inhibition
      potency of some 1,2,3-triazoles having a vicinal diaryl substitution pattern
      along with their ease in synthesis through versatile Ru(II)-catalyzed click
      chemistry make this class of compounds interesting candidates for further design
      and synthesis of highly selective and potent COX-2 inhibitors.

PMID- 19157882
TI  - Application quantum and physico chemical molecular descriptors utilizing
      principal components to study mode of anticoagulant activity of pyridyl chromen-2
      one derivatives.
AB  - Factors II, V, VII and Xa have materialized as a key enzymes for the intervention
      of blood coagulation cascade and for the development of new anti thrombotic
      agents. The combined density functional quantum mechanical/molecular mechanical
      (QM/MM) approach has been used to access inhibition of prothrombin and thrombin
      production. The biological activities of coumarin derivatives as clotting factor
      inhibitors was quantitatively analyzed in terms of physicochemical parameters
      utilizing the principal component analysis. Structural requirements for maximal
      potency were derived from the results of a quantitative structure activity
      relationship analysis.

PMID- 19157883
TI  - Synthetic medicinal chemistry of selected antimalarial natural products.
AB  - Natural products remain a rich source of novel molecular scaffolds for novel
      antimalarial agents in the fight against malaria. This has been well demonstrated
      in the case of quinine and artemisinin both of which have served as templates for
      the development of structurally simpler analogues that either served or continue
      to serve as effective antimalarials. This review will expound on these two
      natural products as well as other selected natural products that have served
      either as antimalarial agents or as potential lead compounds in the development
      of antimalarial drugs.

PMID- 19157884
TI  - Development of 3-substituted-1H-indole derivatives as NR2B/NMDA receptor
      antagonists.
AB  - A combined ligand-based and structure-based approach has previously allowed us to
      identify NR2B/NMDA receptor antagonists containing indole scaffold. In order to
      further explore the main structure activity relationships of this class of
      derivatives we herein report the design, synthesis and biological evaluation of
      new analogues. Some derivatives demonstrated to produce significant
      anticonvulsant properties and NMDA antagonism. The most active of them (3d)
      showed NR2B binding affinity equipotent to that of ifenprodil. These results were
      also corroborated by computational studies.

PMID- 19157885
TI  - Interaction study of bioactive molecules with fibrinogen and human platelets
      determined by 1H NMR relaxation experiments.
AB  - In order to investigate the interaction processes between bioactive molecules and
      macromolecular receptors NMR methodology based on the analysis of selective and
      non-selective spin-lattice relaxation rate enhancements of ligand protons was
      used. The contribution from the bound ligand fraction to the observed relaxation
      rate in relation to macromolecular target concentration allowed the calculation
      of the normalized affinity index[A(I)(N)](L)(T) in which the effects of motional
      anisotropies and different proton densities have been removed. In this paper, we
      applied this methodology to investigate the affinity of epinephrine and
      isoproterenol towards two different systems: fibrinogen and platelets.

PMID- 19157886
TI  - Design, synthesis and SAR studies of 4-allyoxyaniline amides as potent 15
      lipoxygensae inhibitors.
AB  - A group of 4-allyloxyaniline amides 5a-o were designed, synthesized and evaluated
      as potential inhibitors of soybean 15-lipoxygenase (SLO) on the basis of eugenol
      and esteragol structures. Compound 5e showed the best IC(50) in SLO inhibition
      (IC(50)=0.67+/-0.06 microM). All compounds were docked in SLO active site
      retrieved from RCSB Protein Data Bank (PDB entry: 1IK3) and showed that allyloxy
      group of compounds is oriented towards the Fe(3+)-OH moiety in the active site of
      enzyme and fixed by hydrogen bonding with two conserved His(513) and Gln(716). It
      is resulted that molecular volume of the amide moiety would be a major factor in
      inhibitory potency variation of the synthetic amides, where the hydrogen bonding
      of the amide group could also involve in the activity of the inhibitors.

PMID- 19157888
TI  - Focused ion beam milling and ultramicrotomy of mineralised ivory dentine for
      analytical transmission electron microscopy.
AB  - The use of focused ion beam (FIB) milling for preparation of sections of
      mineralised ivory dentine for transmission electron microscopy (TEM) is
      investigated. Ivory dentine is essentially composed of fibrillar type-I collagen
      and apatite crystals. The aim of this project is to gain a clearer understanding
      of the relationship between the organic and inorganic components of ivory dentine
      using analytical TEM, in order to utilise these analytical techniques in the
      context of common skeletal diseases such as osteoporosis and arthritis. TEM
      sections were prepared in both single and dual beam FIB instruments, using two
      standard lift-out techniques, in situ and ex situ. The FIB sections were
      systematically compared with sections prepared by ultramicrotomy, the traditional
      preparation route in biological systems, in terms of structural and chemical
      differences. A clear advantage of FIB milling over ultramicrotomy is that
      dehydration, embedding and section flotation can be eliminated, so that partial
      mineral loss due to dissolution is avoided. The characteristic banding of
      collagen fibrils was clearly seen in FIB milled sections without the need for any
      chemical staining, as is commonly employed in ultramicrotomy. The FIB milling
      technique was able to produce high-quality TEM sections of ivory dentine, which
      are suitable for further investigation using electron energy-loss spectroscopy
      (EELS) and energy-filtering TEM (EFTEM) to probe the collagen/apatite interface.

PMID- 19157889
TI  - Penetrating injury of the maxilla by needlefish jaws.
AB  - INTRODUCTION: Needlefish penetrating injuries have become a worldwide problem,
      inflicting critical morbidities and even mortalities. This is the first published
      case of needlefish injury in the Mediterranean basin. CASE REPORT: A 29 year old
      man was admitted to Meir Medical Centre in Israel with a penetrating facial wound
      caused by elongated needlefish jaws. The severity of the wound contrasted greatly
      with the expected injury from collision with a fish inflicting a small
      penetration lesion. The rigid jaws penetrated the maxilla transversely and
      obliquely from the left canine-fossae, through the nasal cavity, and to the right
      maxillary sinus, with its tip reaching the right medial-inferior orbital wall.
      The needlefish jaws were completely removed using a combined endoscopic and
      external approach. The course of surgery and hospitalization was uneventful and
      the patient was discharged with no complications. CONCLUSIONS: Fish inflicted
      critical facial injuries might be dangerously underestimated prima facie. The
      impact might be energetic enough to penetrate deep facial and vital cranial
      structures, hence thorough examination and imaging are recommended. Needlefish
      species are now common in the tropical and subtropical regions of all oceans and
      therefore this phenomenon is of interest to worldwide trauma medical providers,
      fishermen, divers, and also to marine-biologists.

PMID- 19157887
TI  - Identification of tripeptides recognized by the PDZ domain of Dishevelled.
AB  - The development of inhibitors of Dishevelled (Dvl) PDZ protein-protein
      interactions attracts attention due to a possible application in drug discovery
      and development. Using nuclear magnetic resonance (NMR) spectroscopy, we found
      that a tripeptide VVV binds to the PDZ domain of Dvl, which is a key component
      involved in Wnt signaling. Using a computational approach calculating the binding
      free energy of the complexes of the Dvl PDZ domain and each of the tripeptides
      VXV (X: any amino acid residue except Pro), we found that a tripeptide VWV had
      the highest binding affinity. Consistent with the computational result,
      experimental results showed that the binding of the tripeptide VWV to the Dvl PDZ
      domain was stronger than that of the tripeptide VVV. The binding affinity of the
      tripeptide VWV was comparable to that of the organic molecule NSC668036, which
      was the first identified Dvl PDZ inhibitor. The three-dimensional structure of
      the complex Dvl1 PDZ/VWV was determined to investigate the role of the
      energetically favorable W(-1) residue in binding. These interactions were also
      explored by using molecular dynamic simulation and the molecular mechanics
      Poisson-Boltzmann surface area method. Taken together, these two tripeptides may
      be used as modulators of Wnt signaling or as a scaffold to optimize an antagonist
      for targeting Dvl1 PDZ protein-protein interaction.

PMID- 19157890
TI  - Multi-directional Le Fort III midfacial distraction using an individual
      prefabricated device.
AB  - BACKGROUND: Midfacial distraction following Le Fort III osteotomy has become an
      established procedure for midfacial advancement of syndromic craniosynostosis
      patients. A frequent difficulty is the precise three dimensional (3D) alignment
      of the distracted midface and the proper fixation of the distraction device in
      the midfacial area. In this study we present an individual modification method
      for commercial distraction devices comprising the establishment of prefabricated
      fixation plates and parallel connecting pins. MATERIAL: Individual prefabricated
      fixation plates for the zygomatic buttress were combined with two commercial
      distraction devices. METHOD: The fixation plates were made by a casting technique
      using individual cranial models as templates. The latter were fabricated by the
      rapid prototyping technique of 3D powder printing. For precise realization of the
      distraction vector, two commercial devices were combined and attached rigidly to
      the fixation plates by two parallel pins. RESULT: In the clinical routine, the 3D
      powder printing technique enables the simple fabrication of precise individual
      cranial models, which are required for manufacturing individual fixation plates.
      The combination of two commercial distraction devices facilitates the appropriate
      transfer of complex distraction vectors into the midfacial area. CONCLUSION: The
      technique presented should be useful for a precise multi-directional midfacial
      distraction following Le Fort III osteotomy.

PMID- 19157891
TI  - The 18q deletion syndrome and analysis of the critical region for orofacial cleft
      at 18q22.3.
AB  - INTRODUCTION: The 18q deletion syndrome (18q-) is a multiple-anomaly disorder
      associated with mental retardation, white matter anomalies in the brain, growth
      hormone deficiency, congenital aural atresia, orofacial cleft (OFC), and palate
      abnormalities. The aims of this study were to determine the frequency of
      different forms of OFC in 18q- individuals: cleft palate with or without cleft
      lip (CP/L), cleft lip (CL), and palate abnormalities. We also sought to map a
      potential critical region for OFC within chromosome 18q22.3 region. PATIENTS: The
      study presents an overview of selected 18q- individuals from 11 published reports
      and one presented poster. RESULTS: The frequency of CP/L and CL among 18q-
      individuals is about 25%; when high/arched palate cases are included, the
      frequency rises to about 43%. CONCLUSION: Orofacial abnormalities are
      characteristic features of 18q- syndrome patients and potential CP/L critical
      region could be assumed at 18q22.3 between markers D18S879 and D18S1141. In
      addition, gene deficient mouse models for Sall3 or Tshz1 genes, which are located
      at the 18q22.3 critical region, displayed palate abnormality phenotype.

PMID- 19157892
TI  - A simple colorimetric and ON-OFF fluorescent chemosensor for biologically
      important anions based on amide moieties.
AB  - A simple colorimetric and fluorescent anion chemosensor based on amide moieties,
      6-nitro-1,4-dihydroquinoxaline-2,3-dione has been designed, synthesized and
      characterized by (1)H NMR, ESI-MS and elemental analyses. The strong basic anions
      such as F(-) and AcO(-) resulted in significant decrease in fluorescent emission
      intensity of the compound 1, accompanied synchronously with a dramatic color
      change from colorless to deep yellow in organic medium. (1)H NMR titration
      experiments shed light on the nature of the interactions between 1 and the
      anions.

PMID- 19157894
TI  - President's address at the 2008 SIR Annual Members' Business Meeting.

PMID- 19157893
TI  - Fluorescence microscopy and 3D image reconstruction of cytokine initiated
      disruption of the Parkinson disease associated proteins alpha-synuclein, tau and
      ubiquitin in cultured glial cells.
AB  - Human derived glioblastoma cells were cultured and treated with cytokines
      interleukin-6 (IL6), tumor necrosis factor alpha (TNF) and interferon-gamma (IFN)
      and imaged by fluorescence deconvolution microscopy to localize alpha-synuclein,
      tau and ubiquitin. Exposures were for short (2 h) and prolonged times (up to 96
      h), with doses at both low (10 ng/ml), and high (100 ng/ml) concentrations.
      Further experiments used additive doses up to 200 ng/ml (2 x 100 ng), mimicking a
      super-infection state. Single, low doses of the cytokines initiated changes in
      levels of intracellular proteins, but these changes, be they increases or
      decreases, were not sustained, so we added higher doses of cytokine to the
      culture medium or fresh aliquots of cytokines over time. Finally, we treated
      cells with high, single doses of cytokine (200 ng/ml), to try to sustain
      perturbations of the proteins with cytokines. IFN caused a disruption and
      reduction of peripheral synuclein, TNF treatment resulted in increased levels of
      ubiquitin and IL6 disrupted and appeared to fragment tau. Of note, each of the
      proteins was found in a specific locale, tau being perinuclear, ubiquitin
      residing in the cytoplasm, and alpha-synuclein occupying the tips of cellular
      processes, exhibiting the characteristics of an adhesion protein/molecule [Word
      count=198].

PMID- 19157895
TI  - Development of diaphragmatic weakness after transcatheter arterial
      chemoembolization of the right inferior phrenic artery: frequency and determinant
      factors.
AB  - PURPOSE: To assess the frequency of diaphragmatic weakness and its determinant
      factors after transcatheter arterial chemoembolization of the right inferior
      phrenic artery (IPA) in patients with hepatocellular carcinoma (HCC). MATERIALS
      AND METHODS: From June 2006 to October 2006, 60 patients (48 men, 12 women; mean
      age, 59 years) who had undergone chemoembolization of the right IPA underwent
      follow-up angiography of the right IPA and fluoroscopic diaphragmatic movement
      assessment. Diaphragmatic weakness was determined by the presence of paradoxical
      or decreased movement at fluoroscopy. As determinant factors, the extent of
      embolization (selective chemoembolization of the anterior or posterior branch vs
      nonselective chemoembolization), the use of gelatin sponge pledgets, additional
      cisplatin infusion, the size of a tumor supplied by the right IPA (>or=48 mm vs
      <48 mm), multiplicity of right IPA chemoembolization, and the extent of occlusive
      changes (single vs both branches) at follow-up right IPA angiography were
      assessed. The chi(2) and logistic regression tests were used to identify
      determinant factors of diaphragmatic weakness. RESULTS: Diaphragmatic weakness
      occurred in 11 of the 60 patients (18%). All 11 patients complained of shoulder
      pain during chemoembolization, but persistent dyspnea did not develop.
      Nonselective embolization (P = .005) and occlusive changes of both right IPA
      branches at follow-up angiography (P = .002) were significant determinant
      factors, as determined with univariate analysis. As determined with multivariate
      analysis, an occlusive change of both right IPA branches was the only significant
      determinant factor (P = .009; odds ratio, 17.2). Diaphragmatic weakness developed
      in 10 of the 28 patients (36%) with occlusive changes of both right IPA branches
      and only one (3.1%) of the remaining 32 patients. CONCLUSIONS: When
      chemoembolization of the right IPA is nonselectively performed and with permanent
      occlusive changes of the right IPA, diaphragmatic weakness can develop in one
      third of patients as an ischemic complication.

PMID- 19157896
TI  - Infrapopliteal balloon angioplasty for chronic critical limb ischemia in diabetic
      patients with uremia: when is it worth the effort?
AB  - PURPOSE: To assess the utility of infrapopliteal percutaneous transluminal
      angioplasty (PTA) in diabetic patients with end-stage renal disease and chronic
      critical limb ischemia. MATERIALS AND METHODS: Between 1994 and 2003, 20
      consecutive diabetic patients with uremia (mean age, 59 years; age range, 39-73
      years) underwent infrapopliteal PTA (total of 26 limbs). Additional infrainguinal
      lesions were treated in 12 limbs. Three limbs (12%) were classified as having
      Rutherford category 4 ischemia, 19 (73%) as having category 5 ischemia, and four
      (15%) as having category 6 ischemia. The mean length of the 58 treated
      infrapopliteal lesions was 8.8 cm. RESULTS: Angiographic success (<30% residual
      stenosis) was achieved in 22 of the 26 limbs (85%) and primary clinical success
      (at least one Rutherford category improvement) was achieved in nine (35%). One
      major complication was encountered. PTA was successful in producing a patent
      artery to the ankle level in 18 limbs. Primary clinical success was achieved in
      eight of those 18 limbs (44%) versus only one of the eight limbs (13%) with no
      patent artery after angioplasty (P = .01). When including the four repeated
      interventions, the clinical patency at 1 year (based on physical findings) was
      38% (10 of 26 limbs). The rate of major amputations at 3, 6, and 12 months was
      23%, 31%, and 35%, respectively, with a tendency of increased frequency among
      patients treated for more severe ischemia (Rutherford 4 vs 5 vs 6, P = .10).
      CONCLUSIONS: In diabetic patients with uremia, infrapopliteal PTA should be
      restricted to limbs without extensive tissue loss with lesions estimated to
      facilitate accomplishment of at least one patent artery to the ankle level.

PMID- 19157897
TI  - Intraarterial therapy for acute ischemic strokes.
AB  - PURPOSE: To determine the safety and feasibility of intraarterial stroke therapy
      for acute ischemic strokes at a community-based medical center. MATERIALS AND
      METHODS: This is a retrospective analysis of data gathered from consecutive
      stroke patients treated between June 2004 and April 2007. The following therapies
      were used to treat acute ischemic stroke within 6 hours of symptom onset:
      intraarterial thrombolytic drugs, intraarterial vasodilators, mechanical clot
      retrieval, intravascular stents, and angioplasty. The outcomes measured included
      posttherapy National Institutes of Health Stroke Score (NIHSS), neurologic
      function at 90 days graded according to the modified Rankin Scale (mRS),
      recanalization, symptomatic intracranial hemorrhage, and 90-day mortality.
      RESULTS: Eighty-three patients with a median baseline NIHSS of 17 (range, 3-30)
      were treated with intraarterial therapy. The median posttherapy NIHSS was 5
      (range, 0-33). Forty-two patients (51%) [corrected] had an mRS score of 2 or less
      at 90 days. The recanalization rate was 76%. Five patients (6%) had symptomatic
      intracranial hemorrhage, and the 90-day mortality was 22%. CONCLUSIONS: The
      results of this review showed that an intraarterial therapeutic approach to acute
      ischemic stroke was feasible at a community-based heath center and demonstrated
      encouraging data for outcome and safety.

PMID- 19157898
TI  - Percutaneous transluminal angioplasty balloon inflation with syringes: who needs
      an inflator?
AB  - PURPOSE: High pressures are important in percutaneous transluminal angioplasty,
      particularly in hemodialysis access. Although many operators rely on commercially
      available inflators, small syringes can deliver high pressures, which might make
      inflators unnecessary. Recently introduced polycarbonate (PC) syringes may allow
      higher pressure delivery than traditional polypropylene (PP) ones, so the present
      study was performed to determine predictors of inflation pressures achievable
      with various syringe designs. MATERIALS AND METHODS: Forty-two subjects
      participated: 12 residents, 12 interventional radiology fellows, 12
      interventional radiology attending physicians, and six others. Each subject made
      three attempts to deliver maximum pressure with use of a calibrated gauge for
      each syringe type (1-, 3-, 5-/6-, 10-, and 20-mL PP and PC syringes). A control
      experiment was conducted to assess fatigue effects. Age, sex, grip strength
      measured on a dynamometer, and physical parameters (height, weight, body mass
      index [BMI]) were collected for each participant. RESULTS: Pressures of 40 atm or
      greater were achieved by more than 90% of subjects with 1-mL PC syringes (mean,
      47 atm +/- 7 [SD]). Female subjects generated lower mean pressures with every
      syringe type (P value range, <.0001 to .025); this effect was least pronounced
      with 1-mL PC syringes. Grip strength was highly correlated with pressure
      generation across syringe types. Control experiments showed no significant
      fatigue effect. With rare exceptions, age, BMI, level of training, height, and
      weight did not correlate with pressure generation. CONCLUSIONS: Irrespective of
      sex, grip strength, and BMI, 1-mL PC syringes can be used to generate pressures
      in excess of 40 atm. High correlation between grip strength and pressure
      generation may make it possible to predict the pressure an individual can
      generate with any syringe size or design.

PMID- 19157899
TI  - Endovascular treatment of acute complicated aortic dissection: long-term follow
      up of clinical outcomes and CT findings.
AB  - PURPOSE: To investigate changes of the aorta and affected end organs after
      endovascular treatment of an acute complicated aortic dissection. MATERIALS AND
      METHODS: Twenty patients who underwent endovascular treatment for acute
      complicated aortic dissection were evaluated for computed tomographic (CT)
      findings of the aorta and affected end organs. Three patients had Stanford type A
      dissection and 17 patients had Stanford type B dissection. The follow-up period
      ranged from 3 to 2,719 days (mean, 731 d). The outer diameter of the aorta and
      the inner diameter of the true and false lumen were compared between initial and
      follow-up CT. Renal perfusion, size, and changes of other affected organs were
      evaluated on initial and follow-up CT studies. RESULTS: Branch vessel
      malperfusion improved in 18 of 20 patients (90%). The outer diameter of the aorta
      was increased at all levels (thoracic aorta, 10.9%; abdominal aorta, 11.8%;
      infrarenal aorta, 12.6%). The greatest expansion of aortic false lumen was seen
      in the thoracic aorta (19%). Annual growth rates were 3.64 mm per year in the
      thoracic aorta, 2.64 mm per year at the celiac level of the abdominal aorta, and
      1.42 mm per year in the infrarenal aorta. Affected kidneys showed atrophy in 67%
      of cases in the right kidney and 83% of cases in the left kidney. Limb
      malperfusion improved in 78% of patients, but gallbladder ischemia improved in
      only 33%. CONCLUSIONS: Although fenestration and endovascular stent placement is
      effective for improving acute malperfusion syndrome in type B aortic dissection,
      it cannot prevent delayed expansion of the aorta.

PMID- 19157900
TI  - Self-expanding stent placement as a bridge for safe hepatic chemoembolization in
      a patient with isolated spontaneous dissection of the celiac artery.

PMID- 19157901
TI  - A new wave in treatment of vascular occlusive disease: biodegradable stents-
      clinical experience and scientific principles.
AB  - Stent-based therapies in percutaneous vascular intervention are associated with
      significant long-term complications related to in-stent restenosis. A growing
      body of literature demonstrates the feasibility of biodegradable materials for
      endovascular stents, which may, in theory, circumvent many of the immunologic and
      inflammatory response issues seen with long-term metallic stent failure in
      coronary and peripheral applications. This review describes the history of
      endovascular stents and the challenges encountered with metallic, drug-eluting,
      and biodegradable stents. A review of the basic engineering principles of
      biodegradable stents is provided, along with a discussion of the cellular
      mechanisms of restenosis.

PMID- 19157902
TI  - Emerging technologies subcommittee.

PMID- 19157903
TI  - Covered stents for late postoperative arterial hemorrhage after
      pancreaticoduodenectomy.
AB  - The use of covered stents in treating delayed postoperative hepatic artery
      hemorrhage after pancreaticoduodenectomy may preserve hepatic arterial flow. The
      authors report two cases of massive hemorrhage after pancreaticoduodenectomy that
      were successfully treated with covered stents. Computed tomographic angiography
      demonstrated postprocedure patency of the hepatic arteries at 13 and 15 months,
      respectively. When technically feasible, percutaneous placement of stent-grafts
      may be used as a first-line intervention in delayed hemorrhage after
      pancreaticoduodenectomy.

PMID- 19157904
TI  - Incidence of deep vein thrombosis associated with peripherally inserted central
      catheters in adults with cystic fibrosis.
AB  - PURPOSE: Peripherally inserted central catheters (PICCs) are commonly used in
      patients with cystic fibrosis (CF) to administer intravenous antibiotics for
      pulmonary exacerbations. The aim of this study was to determine the incidence of
      PICC-related deep vein thrombosis (DVT) in a large group of adults with CF with
      and without Burkholderia cepacia complex (BCC) infection, and to investigate the
      association between PICC-related DVT and preinsertion serum erythrocyte
      sedimentation rate (ESR). MATERIALS AND METHODS: This was a retrospective cohort
      study of all patients with PICCs inserted at a single institution during a 6-year
      period. A total of 524 adults with CF were treated in the clinic over this time
      period, with 147 (28.1%) having one or more PICCs inserted. Symptomatic venous
      thromboses were confirmed by Doppler ultrasound. Patients were classified as BCC
      positive or BCC-negative, and preinsertion blood test results were analyzed.
      RESULTS: A total of 376 PICCs were inserted in 147 patients, with 12 patients
      (8.2%) developing symptomatic PICC-related DVT. Five additional subjects (3.4%)
      were diagnosed with asymptomatic PICC-related DVT. BCC-positive patients had a
      higher overall incidence of PICC-related DVT (20.9%) than BCC-negative patients
      (7.7%; P = .02). Preinsertion serum ESRs were higher in patients who subsequently
      developed PICC-related DVT (mean +/- SE, 54.4 mm/h +/- 7.2) compared with those
      without DVT (38.4 mm/h +/- 2.5; P < .05). CONCLUSIONS: The incidence of
      symptomatic PICC-related DVT was 3.7% per PICC. BCC-positive patients had a
      higher overall incidence of DVT than BCC-negative patients. Higher preinsertion
      ESRs in patients who developed PICC-related DVT suggest that systemic
      inflammation may be a risk factor for subsequent PICC-related DVT.

PMID- 19157905
TI  - Stent-graft repair of isolated iliac aneurysms with wide or ectatic necks with
      use of inverted zenith device legs.
AB  - Although there is considerable experience in the management of iliac artery
      aneurysms (IAAs) accompanying abdominal aortic aneurysms, less is known about
      endovascular management of isolated IAAs. The distal landing zone can be secured
      if necessary by extending the graft to the external iliac artery, but the
      proximal landing zone remains a challenging issue, on which technical success is
      dependent. The present report describes a novel technique for endovascular
      management of isolated IAAs with wide proximal necks for which no commercially
      available grafts with fitting sizes exist: inversion of the iliac leg of a Zenith
      device.

PMID- 19157906
TI  - The effect of transarterial prostate embolization in hormone-induced benign
      prostatic hyperplasia in dogs: a pilot study.
AB  - PURPOSE: To evaluate the feasibility of transarterial prostate embolization for
      reducing the volume in hormone-induced canine prostate hyperplasia. MATERIALS AND
      METHODS: Nine beagle dogs were included in this study. Prostate hyperplasia was
      induced by administering dihydrotestosterone and beta-estradiol. The hormones
      were given for 12 weeks in group A (n = 4) and 24 weeks in group B (n = 5).
      Twelve weeks after initiating the hormone treatment, two animals in group A and
      three in group B underwent prostate embolization with polyvinyl alcohol (PVA)
      particles. The volume of each prostate was measured three times with magnetic
      resonance (MR) imaging: once before hormone treatment and at 12 and 24 weeks
      after initiation of hormone administration. The prostates and bladders were
      harvested after the third MR study and were grossly and microscopically
      evaluated. RESULTS: The mean volume of the prostate increased by 156.13% +/-
      110.01% in the nine dogs after 12 weeks of hormone administration. In group A (n
      = 4), the third MR study showed a 67.74% mean decrease in prostate volume in
      nonembolized dogs and an 81.04% mean decrease in embolized dogs compared with the
      second MR study. In group B (n = 5), the mean increases in prostate volume
      between the second and third MR studies were 40.79% in embolized dogs (n = 3) and
      75.15% in nonembolized dogs. There was no gross or microscopic change in the
      bladders except for a focal hemorrhage in one specimen. CONCLUSIONS:
      Transcatheter arterial embolization is feasible for reducing prostate volume
      without serious complications in hormone-induced canine prostate hyperplasia.

PMID- 19157907
TI  - Conflicts of interest in the development of new interventional medical devices.

PMID- 19157908
TI  - Botulinum toxin A injection of salivary glands in children with drooling and
      chronic aspiration.
AB  - PURPOSE: To review outcomes of ultrasound (US)-guided percutaneous submandibular
      gland injection of botulinum toxin A (BTX-A) in the treatment of drooling and
      chronic aspiration. MATERIALS AND METHODS: A 3-year retrospective review was
      performed of 220 US-guided salivary gland injections in 36 patients. There were
      21 male patients and 15 female patients with an age range of 1.4 to 19.8 years
      (mean, 8.6 y) and a weight range of 7.8 to 73 kg (mean, 24.4 kg). The mean
      pretreatment analysis period was 48 months and the mean follow-up period was 21
      months. The study group was divided into groups with anterior (n = 9) and
      posterior (n = 27) drooling, with those with both (n = 10) included in the
      posterior group. RESULTS: All procedures were technically successful. Bilateral
      submandibular injections were performed in 34 procedures and bilateral
      submandibular and parotid injections were performed in 38 procedures. Of the 27
      patients with posterior drooling, improvement occurred in 24 patients (88%), no
      improvement was seen in two (8%), and one (4%) was lost to follow-up. Of the nine
      patients with anterior drooling, six (66%) showed improvement, there was no
      response in two (22%), and one (12%) was lost to follow-up. The total number of
      hospitalizations for respiratory issues and presumed aspiration pneumonia
      decreased by 56.4% per year in the patients with posterior drooling. There was
      one procedure-related complication: an episode of self-limited oral bleeding.
      CONCLUSION: Salivary gland BTX-A injection for salivary control shows promising
      results in decreasing saliva production and frequency of respiratory symptoms in
      children with drooling and chronic aspiration.

PMID- 19157909
TI  - Preoperative statin administration is associated with lower mortality and
      decreased need for postoperative hemodialysis in patients undergoing coronary
      artery bypass graft surgery.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of perioperative
      statin administration on renal outcomes after cardiac surgery. DESIGN: A
      retrospective chart review. SETTING: A university hospital. PARTICIPANTS:
      Patients presenting for cardiac surgery. INTERVENTIONS: The records of 2,760
      patients admitted for coronary artery bypass graft (CABG) surgery from 1997 to
      2006 were reviewed. In-hospital mortality, the need for renal replacement therapy
      (RRT), and acute renal failure (ARF) were considered the primary outcomes.
      Univariate and multiple logistic regression analyses were performed to assess the
      relationship between each outcome and statin therapy while adjusting for other
      patient characteristics. MAIN RESULTS: Of the 2,760 patients, 1,557 were taking
      preoperative statins. On univariate analysis, the mortality rate for patients
      receiving statins was 2.4% versus 4.2% for those not receiving statins (p =
      0.008). The requirement for RRT was 1.9% for patients receiving statins versus
      3.6% for those not receiving statins (p = 0.011). The incidence of ARF was not
      statistically significant between groups (28% v 27.5%). On multivariate analysis,
      statin therapy was associated with a 43% decrease in the risk of death and a 46%
      decrease in the risk of RRT, but statins were not associated with a decreased
      risk of ARF. Also, the beneficial effects of statins were age-dependent, with
      younger patients experiencing a greater advantage. CONCLUSIONS: The preoperative
      use of statins is associated with decreased in-hospital mortality and a reduction
      in the need for RRT.

PMID- 19157910
TI  - Normal shoulder outcome score values in the young, active adult.
AB  - BACKGROUND: Our objective was to determine baseline, normative values for
      multiple shoulder outcome scores in a young, active population without shoulder
      symptoms. METHODS: One hundred ninety-two volunteers completed the Single
      Assessment Numeric Evaluation, modified American Shoulder and Elbow Surgeons
      score, Western Ontario Shoulder Instability index, Simple Shoulder Test, and
      Disabilities of the Arm, Shoulder and Hand score. Their mean age was 28.8 years
      (range, 17-50 years). RESULTS: Of the participants, 59 (31%) scored no
      deficiencies on any of the outcome instruments, whereas 133 (69%) demonstrated
      some abnormal shoulder score. The mean scores were as follows: Single Assessment
      Numeric Evaluation, 97.7 (SD, 5.2); modified American Shoulder and Elbow Surgeons
      score, 98.9 (SD, 3.3); Western Ontario Shoulder Instability index, 82.7 of 2100
      (SD, 153.5); Simple Shoulder Test, 11.79 (SD, 0.60); and Disabilities of the Arm,
      Shoulder and Hand score, 1.85 (SD, 5.99). CONCLUSION: Our results show that the
      best possible shoulder score in an asymptomatic population may not be equivalent
      to a perfect score on the outcome scale.

PMID- 19157911
TI  - Tuberosity position correlates with fatty infiltration of the rotator cuff after
      hemiarthroplasty for proximal humeral fractures.
AB  - HYPOTHESIS: This study investigates the correlation between tuberosity
      positioning, fatty infiltration of the rotator cuff, and clinical outcome after
      hemiarthroplasty for proximal humeral fracture. MATERIALS AND METHODS: Twenty
      patients with a mean age of 70.8 +/- 9.9 years were evaluated at a mean of 19.8
      +/- 9.4 months. Evaluation included assessment of the Constant score (CS);
      Disabilities of the Arm, Shoulder and Hand (DASH) score; radiographic evaluation;
      and computed tomography to classify healing of the tuberosities and changes in
      the rotator cuff. Fatty degeneration of the cuff was classified according to the
      Goutallier classification as stage 0 to 4. Tuberosity positioning was classified
      as mal-positioning of less than 0.5 cm., 0.5 to 1 cm., >1.0 cm., or not healed.
      RESULTS: The mean Constant Score (CS) of patients with greater tuberosity
      displacement of <0.5 cm was significantly higher than the CS of patients with >
      or =0.5 cm displacement and non-united greater tuberosities. The CS of patients
      with greater tuberosity displacement of 0.5 to 1 cm was significantly higher than
      that in patients with non-united greater tuberosities. For the lesser tuberosity,
      patients with displacement of <0.5 cm showed significantly higher outcome scores
      than patients with displacement of >1 cm and non-united lesser tuberosities.
      There was a significant correlation between fatty infiltration of the
      supraspinatus and infraspinatus muscles and greater tuberosity malposition and
      between fatty infiltration of the subscapularis and lesser tuberosity
      malposition. CONCLUSION: Fatty infiltration of the cuff was significantly
      associated with lower clinical scores. Tuberosity positioning and healing are
      critical for improved clinical outcomes after hemiarthroplasty for proximal
      humeral fractures.

PMID- 19157912
TI  - Intraosseous ganglion of the glenoid causing suprascapular nerve entrapment
      syndrome: a case report.

PMID- 19157913
TI  - Central and peripheral region tibial plateau chondrocytes respond differently to
      in vitro dynamic compression.
AB  - OBJECTIVE: The objective of this study was to test the hypotheses that
      chondrocytes from distinct regions of the porcine tibial plateau: (1) display
      region-specific baseline gene expression, and (2) respond differently to in vitro
      mechanical loading. METHODS: Articular cartilage explants were obtained from
      central (not covered by meniscus) and peripheral (covered by meniscus) regions of
      porcine tibial plateaus. For baseline gene expression analysis, samples were snap
      frozen. To determine the effect of mechanical loading, central and peripheral
      region explants were exposed to equivalent dynamic compression (0-100 kPa) and
      compared to site-matched free-swelling controls (FSCs). mRNA levels for type II
      collagen (CII), aggrecan (AGGR), matrix metalloproteinase 1 (MMP-1), MMP-3, MMP
      13, A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAM-TS4),
      ADAM-TS5, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, and tumor
      necrosis factor alpha (TNFalpha) were quantified using real time polymerase chain
      reaction (RT-PCR). RESULTS: At baseline, mRNA levels for the structural proteins
      CII and AGGR were approximately twofold greater in the central region compared
      with peripheral region explants. In vitro dynamic compression strongly affected
      expression levels for CII, AGGR, MMP-3, and TIMP-2 relative to FSCs. Response
      differed significantly by region, with greater upregulation of CII, AGGR, and MMP
      3 in central region explants. CONCLUSIONS: Chondrocytes from different regions of
      the porcine tibial plateau express mRNA for structural proteins at different
      levels and respond to equivalent in vitro mechanical loading with distinctive
      changes in gene expression. These regional biological variations appear to be
      related to the local mechanical environment in the normal joint, and thus may
      indicate a sensitivity of the joint to conditions that alter joint loading such
      as anterior cruciate ligament (ACL) injury, meniscectomy, or joint instability.

PMID- 19157914
TI  - The accuracy of image guided surgery based on cone beam computer tomography image
      data.
AB  - OBJECTIVE: The objective of this study was to verify if accurate patient-to-image
      registration for precision navigation in maxillofacial surgery is possible based
      on cone beam computed tomography (CBCT) image data. STUDY DESIGN: A maxillary
      registration template was placed on a standard plastic skull phantom that was
      equipped with a custom made model of the maxilla and with target markers. Imaging
      was performed with a CBCT device (Newtom 9000 Digital Volume Tomograph (DVT), QR
      s.r.l., Verona, Italy) and a computed tomography (CT) scanner (Somatom 4,
      Siemens, Forchheim, Germany). Using an infrared navigation system (Polaris, NDI,
      Waterloo, Ontario), multiple pair-point registration of both image data sets and
      the phantom were performed. The target registration error (TRE) was evaluated.
      RESULTS: A total of 243 registrations were performed for either image data set.
      The spatial distribution of TRE on the skull showed increasing inaccuracy with
      growing distance from the registration markers. The average target registration
      error was 1.50 +/- 0.82 mm with CBCT and 1.57 +/- 0.84 mm with CT image data and
      did not differ significantly. Error distribution correlated strongly between CT-
      and CBCT-based registration. CONCLUSIONS: The overall registration accuracy based
      on CBCT image data was similar to CT. The strong correlation of the geometric
      distribution of TRE between CT- and CBCT-based measurements proves that CBCT can
      be equivalent to CT in image-guided maxillofacial surgery.

PMID- 19157915
TI  - Tuberculosis of the head and neck: a review of 20 cases.
AB  - OBJECTIVE: Tuberculosis (TB) of the head and neck is currently a reemerging
      infectious disease and may be a diagnostic challenge for dental care providers.
      The aim of the present study was to retrospectively review the clinical features
      of patients diagnosed with TB of the head and neck during the past 16 years.
      MATERIALS AND METHODS: Thirteen male and 7 female patients with TB of the head
      and neck were histologically identified following surgical biopsy in our
      department between 1991 and 2007. The medical charts were reviewed. RESULTS: The
      age distribution was broad, with 11 patients (55%) older than 50 years and 4
      (20%) younger than 10 years old. Thirteen patients had oral lesions and 2 had
      multiple lesions. The most common oral location was the buccal mucosa and/or
      vestibule (5 cases), followed by the alveolar mucosa (4 cases), palate (2 cases),
      lip (2 cases), and tongue (1 case). Seven patients had cervical TB. The
      predominant clinical manifestation was ulceration. Two patients were found to
      have coexistent metastatic squamous cell carcinoma. Four patients were identified
      with active pulmonary lesions and 1 patient with evidence of old pulmonary TB on
      the 14 chest radiographs available. CONCLUSION: Tuberculosis of the head and neck
      may not be as rare as once thought. We emphasize the importance of early
      diagnosis in such lesions, especially in slow-to-heal wounds and undiagnosed neck
      lumps.

PMID- 19157916
TI  - Efficacy of sodium hypochlorite combined with chlorhexidine against Enterococcus
      faecalis in vitro.
AB  - The aim of this study was to investigate in vitro the efficacy of the combination
      of sodium hypochlorite (NaOCl) and chlorhexidine (CHX) in different
      concentrations against Enterococcus faecalis compared with the antimicrobial
      activity of the same irrigating substances when applied alone. The substances
      tested were 2.0% CHX gel, 2.0% CHX liquid, 1% NaOCl, 2.5% NaOCl, 5.25% NaOCl, and
      combinations of them in the same proportions. Two methods were used: the agar
      diffusion test and the broth dilution test. The largest mean microbial growth
      zone was obtained by 2.0% CHX gel, and the smallest zones were obtained by 1% and
      2.5% NaOCl (P < .05). 2.0% CHX (gel and liquid formulation), 5.25% NaOCl, and the
      combination of 2.0% CHX liquid and 5.25% NaOCl, all of which needed <or=1 min to
      eliminate E. faecalis. The association of NaOCl and CHX did not improve the
      antimicrobial activity of CHX alone.

PMID- 19157917
TI  - The relationship between sialographic images and clinical symptoms of
      inflammatory parotid gland diseases.
AB  - OBJECTIVE: The objective of this study was to evaluate the relationship between
      sialographic images and clinical symptoms of inflammatory parotid gland diseases.
      MATERIALS AND METHODS: Clinical symptoms including swelling, pain, the duration
      of these symptoms, and degree of salivation were examined on 83 parotid glands
      from 64 patients. Swelling and pain were classified into 4 categories. Duration
      of any symptom was recorded in months and the degree of salivation was classified
      into 4 groups by inspection and massage. Sialography was performed and panoramic
      radiographs were taken later to examine the evacuation state of the contrast
      medium. The degree of inflammation on sialographic images was evaluated in 3
      areas (the main duct, the intraglandular duct, and the parenchyma) by rating 4
      grades respectively under the consensus of 3 radiologists. A Fisher's exact test
      and a Pearson correlation were used for statistical analyses. RESULTS: The degree
      of salivation showed significant correlation between the presence of inflammation
      and the grades of inflammation on sialographic images. There was also a
      correlation between the grades of inflammation of the sialographic images and the
      amount of retention of the contrast medium. There was no significant relationship
      between the grades of inflammation of the sialographic images with swelling or
      pain. CONCLUSION: The grade of inflammation of a sialographic image has
      correlated with a degree of salivation.

PMID- 19157918
TI  - Bilateral coronoid hyperplasia (Jacob disease on right and elongation on left):
      report of a case and literature review.
AB  - A case is reported of bilateral coronoid hyperplasia. The literature is reviewed
      concerning this condition's etiology, pathogenesis, clinical characteristics,
      diagnosis, and treatment. Jacob disease and coronoid elongation are both clinical
      features of coronoid hyperplasia. It is usually accompanied by restricted
      opening. The etiology and pathogenesis of coronoid hyperplasia are unclear. The
      condition can be diagnosed by panoramic radiographs and with 3-dimensional
      reconstructions from computerized tomography image data sets. Hyperplasia of the
      coronoid processes can be treated using an intraoral approach for coronoidectomy
      and dynamic laser physiotherapy after surgery. Although hyperplasia of the
      coronoid processes is uncommon in clinic, it can be found through careful
      examination and proper radiographic study. A 39-year-old female patient was
      referred for coronoid hyperplasia (Jacob disease on right and elongation on
      left). The histologic diagnosis for the right condylar condition was
      osteochondroma.

PMID- 19157919
TI  - The use of corticosteroids and nonsteroidal antiinflammatory medication for the
      management of pain and inflammation after third molar surgery: a review of the
      literature.
AB  - The use of medication to relieve pain and inflammation after removal of third
      molars has been explored thoroughly in the literature. Narcotic analgesics,
      nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, and combinations
      of these all have a role in the postoperative management of pain and swelling
      within this group of patients. This article addresses the use of NSAIDs and
      corticosteroids after third molar surgery, along with a review of the literature,
      which is incorporated to provide practitioners helpful, quick, and reliable
      information regarding patients undergoing third molar surgery.

PMID- 19157920
TI  - Effects of different irrigation regimens on the sealing properties of repaired
      furcal perforations.
AB  - OBJECTIVE: The pulp chamber is inevitably exposed to irrigants during endodontic
      therapy. This study aimed to investigate whether different irrigation regimens
      would alter the sealing ability of repaired furcal perforations. STUDY DESIGN:
      Pulp chambers of 90 extracted human molars were accessed, after which
      standardized diamond bur-cut perforations were created in the center of the pulp
      chamber floor. The canal orifices and the apical end of roots were sealed with
      acid-etch composite resin. Eighty teeth were randomly divided into 2 groups (n =
      40/group) according to the material used for repairing the perforation defects:
      (1) Mineral trioxide aggregate (MTA), (2) Super-EBA. The remaining teeth (n = 10)
      served as controls. The specimens were further subgrouped according to the
      irrigation regimens applied over the repair site (n = 10/group): (a) 5.25% NaOCl,
      (b) 5.25% NaOCl + EDTA, (c) 5.25% NaOCl + MTAD, and (d) No irrigation. Coronal
      leakage was measured by the fluid-filtration method at 1 day and 1 week. RESULTS:
      Fluid conductance was not affected by the type of repair material (P = .964) or
      time (P = .726), but was affected significantly by the irrigation regimens in the
      following ranking: (P < .001): NaOCl < or = No Irrigation < NaOCl + MTAD < or =
      NaOCl + EDTA. CONCLUSION: The sealing ability of furcal perforations repaired
      with MTA or Super-EBA were differentially affected by exposure to the tested
      irrigation regimens.

PMID- 19157922
TI  - Direct-to-consumer advertising for oral cancer screening devices.

PMID- 19157921
TI  - A rapid nondestructive method for root dentin moisture measurements: in vitro
      pilot study.
AB  - Dentin moisture content is important in adhesive bonding and structural strength
      research; however, there is no rapid method available to assess dentin moisture
      without sample destruction. This study examined the use of a digital grain
      moisture meter to measure root dentin moisture in vitro. Extracted mandibular
      single-rooted teeth were sectioned at the CEJ. The moisture of the root dentin
      was measured at 6 measuring modes for different grains and repeated 5 times.
      Dentin weight changes before and after drying were measured to obtain control
      values. The control values were compared with machine readings. In conclusion,
      (1) each nondestructive measurement took less than 30 seconds, (2) 24 hours of
      storage at 37 degrees C and 100% humidity did not restore dentin moisture, and
      (3) 5 grain modes had a high validity and could be used for dentin moisture
      measurements.

PMID- 19157923
TI  - Chemical composition, radiopacity, and biocompatibility of Portland cement with
      bismuth oxide.
AB  - OBJECTIVE: This study compared the chemical constitution, radiopacity, and
      biocompatibility of Portland cement containing bismuth oxide (experimental
      cement) with those of Portland cement and mineral trioxide aggregate (MTA). STUDY
      DESIGN: The chemical constitution of materials was determined by scanning
      electron microscopy and energy-dispersive X-ray analysis. The radiopacity of the
      materials was determined using the ISO/6876 method. The biocompatibility of the
      materials was tested by MTT assay and tissue reaction. RESULTS: The constitution
      of all materials was similar. However, the Portland cement and experimental
      cement were more irregular and had a larger particle size than MTA. The
      radiopacity of the experimental cement was similar to MTA. The MTT assay revealed
      MTA to have slightly higher cell viability than the other materials. However,
      there were no statistically significant differences between the materials, with
      the exception of MTA at 24 h. There was no significant difference in the tissue
      reaction between the experimental groups. CONCLUSIONS: These results suggest that
      the experimental cement may be used as a substitute for MTA.

PMID- 19157924
TI  - Early gene expression analyzed by a genome microarray and real-time PCR in
      osteoblasts cultured with a 4-META/MMA-TBB adhesive resin sealer.
AB  - OBJECTIVES: Adhesive resin sealer systems have been applied in endodontics to
      seal the root canal system. This study was designed to confirm the mechanism of
      intracellular molecular events in an in vitro cell culture system with a 4
      methacryloxyethyl trimellitate anhydride/methylmethacrylate-tri-n-butyl borane (4
      META/MMA-TBB) adhesive resin sealer. STUDY DESIGN: The gene expression patterns
      relating to cell growth and differentiation were examined using a human genome
      expression microarray and real-time polymerase chain reaction analyses in hard
      tissue-forming osteoblasts cultured with and without a 4-META/MMA-TBB resin
      sealer. RESULTS: There was no significant difference in the cell number between
      the control and adhesive sealer groups. An increased expression of integrin beta,
      transforming growth factor beta-related protein, craniofacial development protein
      1, and PI3K genes was demonstrated. The integrin beta and PI3K genes showed
      extremely high ratios. CONCLUSIONS: The signal transduction pathway, at least
      through the PI3K/Akt cascade for cell proliferation and differentiation, can be
      controlled by some components of this type of adhesive resin sealer.

PMID- 19157925
TI  - A case report of Gardner syndrome with hereditary widespread osteomatous jaw
      lesions.
AB  - Gardner syndrome (GS) is an abnormality of familial adenomatous polyposis
      accompanied by characteristic jaw lesions. Gardner syndrome intestinal polyps
      have a 100% risk of undergoing malignant transformation; consequently, early
      identification and surgical intervention of the disease are important to prolong
      the life of the patient. We present a case of GS in a 55-year-old woman. Familial
      adenomatous polyposis, osteomatous jaw and ocular lesions, several dental
      abnormalities, and an abdominal desmoid tumor are the characteristic features of
      this case. This case demonstrates the presence of unusual, widespread,
      hereditary, osteomatous jaw lesions that caused diagnostic confusion with
      familial gigantiform cementoma.

PMID- 19157926
TI  - A case of basal cell adenocarcinoma of the upper gingiva.
AB  - Basal cell adenocarcinoma arising from the minor salivary gland is extremely
      rare. We report a 76-year-old Japanese man with basal cell adenocarcinoma
      originating in the upper gingiva. He underwent subtotal maxillectomy combined
      with resection of the coronoid process, and reconstruction was performed using a
      rectus abdominis microvascular flap. The patient has been followed for 40 months
      after operation without any evidence of disease.

PMID- 19157927
TI  - Peripheral clear cell variant of calcifying epithelial odontogenic tumor
      affecting 2 sites: report of a case.
AB  - A case of clear cell variant of calcifying epithelial odontogenic tumor (CEOT)
      affecting 2 different extraosseous sites is described. A 43-year-old female
      patient presented with 2 gingival lesions (1 in the upper premolar and 1 in the
      lower incisor area), which were clinically diagnosed as inflammatory hyperplasia
      and surgically removed. Microscopically, both lesions were composed of polyhedral
      cells (some with clear cytoplasm); hyaline material and areas of calcification
      were also observed. The diagnostic hypotheses raised were clear cell variant of
      CEOT, hyalinizing clear cell carcinoma, and renal metastasis. The hyaline
      material was positive for Congo red, crystal violet, and Lugol's iodine stains,
      but negative for Coomassie blue; the clear cells showed positively stained
      granules with PAS stain. Based on these results, the conclusive diagnosis for
      both lesions was clear cell variant of CEOT. No evidence of recurrence was
      observed after 1 year of follow-up.

PMID- 19157928
TI  - Control of bovine virus diarrhoea at the herd level: reducing the risk of false
      negatives in the detection of persistently infected cattle.
AB  - The need to detect and eliminate cattle persistently infected (PI) with bovine
      viral diarrhoea virus (BVDV) is key to the control of BVD and has been shown to
      be very effective in eradicating BVDV from infected herds. However, because of
      pitfalls in the detection procedures, some PI animals can be missed and, as a
      result, are not identified and removal is delayed. The high prevalence of BVDV in
      cattle populations in some countries (such as Belgium and neighbouring countries)
      means there is a high risk of reinfection of a herd from which BVDV has been
      eradicated. Based on both practical experience and a literature study, this
      review considers those points that are critical to minimising the number of false
      negatives in the detection of PI cattle.

PMID- 19157929
TI  - The effect of caprine arthritis encephalitis virus infection on production in
      goats.
AB  - Three consecutive years of monitoring 248 goats in the same flock, found that the
      first lactation milk yield was significantly higher in seronegative (578L) than
      in seropositive (447L) animals but this difference disappeared in the subsequent
      second to fourth lactations. No significant differences were found in the
      proportions of seronegative and seropositive does in the flock, the percentage of
      animals culled, the number of offspring, or in the number of cases of udder
      bacterial infection, irrespective of age. Removal of kids from their dams before
      suckling and the feeding of pasteurised colostrum resulted in reduced numbers of
      seropositive animals. Nevertheless, by approximately 24 months of age, 76.9% of
      these initially seronegative animals were seropositive, a factor that
      significantly contributed to flock seropositivity. This finding could be
      attributed to lateral virus transmission from seropositive to seronegative kids
      because of lack of segregation within the flock.

PMID- 19157930
TI  - Early onset primary dystonia.
AB  - Dystonia is a syndrome characterized by sustained muscle contractions, frequently
      causing twisting and repetitive movements or abnormal postures. It is classified
      by age at onset, by distribution, and by aetiology. The aetiological
      classification distinguishes the following categories: primary, dystonia plus,
      secondary, heredo-degenerative and psychogenic dystonia. Primary dystonia is
      defined as clinical condition characterized by dystonia as the only neurological
      abnormality apart from tremor. Different genetic alterations and gene loci have
      been mapped in familial and sporadic patients. Early onset-primary dystonia (EO
      PD) is the most severe form of primary dystonia, with clinical and genetic
      heterogeneity. It usually starts in one body part, subsequently spreads to
      involve other body regions with frequent generalization. DYT1 dystonia is
      transmitted as an autosomal dominant trait with reduced penetrance. The unique
      underlying mutation is a GAG deletion in the coding region of the TOR1A gene,
      located at chromosome 9q34. DYT16 dystonia is a novel recessive form of EO-PD,
      recently described in few patients, caused by mutations in the PRKRA gene located
      at chromosome 2q31. At least other two loci have been mapped, but there remains a
      large number of patients with EO-PD in whom no genetic alteration is discovered.

PMID- 19157931
TI  - Dipolar recoupling in solid state NMR by phase alternating pulse sequences.
AB  - We describe some new developments in the methodology of making heteronuclear and
      homonuclear recoupling experiments in solid state NMR insensitive to rf
      inhomogeneity by phase alternating the irradiation on the spin system every rotor
      period. By incorporating delays of half rotor periods in the pulse sequences,
      these phase alternating experiments can be made gamma encoded. The proposed
      methodology is conceptually different from the standard methods of making
      recoupling experiments robust by the use of ramps and adiabatic pulses in the
      recoupling periods. We show how the concept of phase alternation can be
      incorporated in the design of homonuclear recoupling experiments that are both
      insensitive to chemical shift dispersion and rf-inhomogeneity.

PMID- 19157932
TI  - Pulsed EPR imaging of nitroxides in mice.
AB  - Nitroxides, unlike trityl radicals, have shorter T(2)s which until now were not
      detectable in vivo by a time-domain pulsed Electron Paramagnetic Resonance (EPR)
      spectrometer at 300 MHz since their phase memory times were shorter than the
      spectrometer recovery times. In the current version of the time-domain EPR
      spectrometer with improved spectrometer recovery times, the feasibility of
      detecting signals from nitroxide radicals was tested. Among the nitroxides
      evaluated, deuterated (15)N-Tempone ((15)N-PDT) was found to have the longest
      T(2). The signal intensity profile as a function of concentration of these agents
      was evaluated and a biphasic behavior was observed; beyond a nitroxide
      concentration of 1.5mM, signal intensity was found to decrease as a result of
      self-broadening. Imaging experiments were carried out with (15)N-PDT in solutions
      equilibrated with 0%, 5%, 10%, and 21% oxygen using the single point imaging
      (SPI) modality in EPR. The image intensity in these tubes was found to depend on
      the oxygen concentration which in turn influences the T(2) of (15)N-PDT. In vivo
      experiments were demonstrated with (15)N-PDT in anesthetized mice where the
      distribution and metabolism of (15)N-PDT could be monitored. This study, for the
      first time shows the capability to image a cell-permeable nitroxide in mice using
      pulsed EPR in the SPI modality.

PMID- 19157933
TI  - Role of polymerase chain reaction in early diagnosis of herpes zoster
      ophthalmicus in children.
AB  - Herpes zoster ophthalmicus is uncommon in children, and diagnosis may be delayed
      until the typical skin lesions become apparent. Delay in appropriate treatment
      may result in sight-threatening complications. We report a case of an 18-month
      old child in whom we promptly confirmed the clinical suspicion of herpes zoster
      ophthalmicus by the identification of viral DNA using polymerase chain reaction.
      This procedure enabled us to administer prompt antiviral treatment, preventing
      sight-threatening sequelae. We review the literature regarding the possible
      mechanism of herpes zoster ophthalmicus in immunocompetent children and discuss
      the role of polymerase chain reaction in its diagnosis.

PMID- 19157934
TI  - Sub-Tenon's space abscess after strabismus surgery.
AB  - Inflammatory orbital complications of strabismus surgery are a rare occurrence.
      They include cellulitis, subconjunctival and sub-Tenon's abscesses, myositis, and
      endophthalmitis. The incidence of periocular infection is assumed to be one case
      per 1,100 surgeries. In this report, we describe a case of sub-Tenon's abscess
      after strabismus surgery.

PMID- 19157935
TI  - Decreased postoperative drift in intermittent exotropia associated with A and V
      patterns.
AB  - INTRODUCTION: Few data exist concerning postoperative drift in patients with
      intermittent exotropia who have coexistent A or V patterns. In addition, the
      impacts of pattern collapse and surgical method on postoperative drift have not
      been well addressed. METHODS: We retrospectively reviewed the records of 132
      patients who had surgery for intermittent exotropia and had >or=6 months' follow
      up. Mean postoperative drift in 66 patients with pattern exotropia was compared
      with a nonpattern (comitant) group matched for surgeon, age, surgical method, and
      initial deviation. Postoperative drift was calculated by subtracting the
      deviation at postoperative day 1 from that at approximately 6 weeks, 6 months, 9
      months, and >1 year. RESULTS: Pattern and comitant groups were similar in mean +/
      SD age (15 +/- 17 years), follow-up (2.3 +/- 2 years), preoperative exotropia
      (23(Delta) +/- 11(Delta)), initial postoperative deviation (1(Delta) +/- 5(Delta)
      esotropia), and surgical technique. Patients with pattern intermittent exotropia
      showed significantly (p < 0.02) less exotropic drift postoperatively at all times
      than did patients without a pattern. In contrast to undercorrected patients, in
      those who were sufficiently overcorrected, the effect of pattern became
      statistically insignificant after 6 months. Patients with persisting
      postoperative patterns had a significantly less postoperative drift (p < 0.01).
      CONCLUSION: Postoperative drift in patients with A- or V-pattern intermittent
      exotropia is consistently less than in comitant exotropia, particularly if the
      pattern persists postoperatively and if the exotropia is undercorrected.
      Therefore, surgeons should consider smaller early overcorrections in pattern than
      comitant intermittent exotropia. Lesser postoperative drift in pattern exotropia
      may suggest differing underlying causes of pattern vs nonpattern exotropia.

PMID- 19157936
TI  - Reversal of optic neuropathy secondary to voluntary globe luxation.
AB  - Luxation of the globe is rare in the general population and may be spontaneous,
      voluntary, or traumatic. Spontaneous or voluntary globe luxation results from
      shallow orbit, floppy eyelids, lax orbital ligaments, backward displacement of
      orbital septum, or proptotic eyes due to orbital tumors or infiltrative
      processes, as in Grave's ophthalmopathy. The authors report a case with
      unilateral voluntary globe luxation presented with unilateral progressive visual
      loss.

PMID- 19157937
TI  - The influence of head tilt on ocular torsion in patients with superior oblique
      muscle palsy.
AB  - INTRODUCTION: Patients with superior oblique muscle palsy often assume a
      compensatory head tilt to the contralateral side of the affected eye. This tilt
      serves to decrease the hypertropia and, in theory, might decrease the
      excyclotropia. METHODS: A prospective investigation was undertaken of the effect
      of forced head tilt to the right and left on torsion and the hypertropia in
      patients with unilateral superior oblique muscle palsy. RESULTS: Twenty patients
      with unilateral superior oblique muscle palsy had a mean decrease in their
      hypertropia of 6.4(Delta) +/- 3.9(Delta) on forced head tilt from the head-erect
      position toward the contralateral side (95% CI, 4.7-8.1). This finding
      represented a decrease of 62% of the hypertropia found in the head-erect
      position. The difference was significant (p < 0.001, paired t-test). The mean
      decrease of the excyclotropia was only 0.25 degrees +/- 0.6 degrees on
      contralateral head tilt, which represented 3% of the excyclotropia in the head
      erect position. This difference was not significant (p < 0.06). The percent by
      which the hypertropia decreased from the head-erect position to that found on
      contralateral head tilt was significantly greater than the amount by which the
      excyclotropia decreased (p < 0.001). CONCLUSIONS: With contralateral head tilt,
      patients with superior oblique muscle palsy demonstrate a significant decrease in
      their hypertropia but essentially no change in their excyclotropia. The
      compensatory head tilt they manifest appears to serve the purpose of decreasing
      the vertical but not the torsional misalignment.

PMID- 19157938
TI  - Evaluation of vision-specific quality-of-life in albinism.
AB  - INTRODUCTION: Human albinism is a genetic condition associated with visual
      impairment that affects many aspects of daily life. Office measurements of visual
      acuity do not necessarily reflect daily visual function and health status. This
      study used the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to
      determine the effect of albinism-associated ophthalmopathy on quality of life
      (QOL). METHODS: We administered the NEI-VFQ, which consists of 25 questions about
      QOL (VFQ-25) and 14 questions about well-being (VFQ-39), to 44 consenting
      participants with albinism older than the age of 18 years. RESULTS: Nineteen male
      and 25 female subjects completed the study. Median age was 30.5 years (range, 18
      79 years). Mean best-corrected visual acuity was 20/83 (range, 20/20 to 20/320).
      Forty-eight percent reported that they were currently able to drive with their
      condition. Participants perceived midscale problems with their general vision
      (median subscale score 60.0). Visual acuity correlated moderately with overall
      NEI-VFQ composite scores (r(s) = 0.40, p = 0.01 for VFQ-25 and r(s) = 0.36, p =
      0.02 for VFQ-39). Most notable impairment was recorded for distance acuity,
      vision-specific mental health, and vision-specific role difficulties (VFQ-39
      median subscale scores 66.7, 70.0, and 75.0, respectively). Differences by sex
      were insignificant. Greater ceiling effects were noted for the VFQ-25 than for
      the VFQ-39. CONCLUSIONS: The NEI-VFQ-39 is a method to evaluate self-reported
      effects of vision-related QOL in albinism and may be used as a baseline for
      evaluating outcomes in interventional studies in these patients.

PMID- 19157939
TI  - Unilateral amblyopia: An optical coherence tomography study.
AB  - PURPOSE: To determine whether retinal nerve fiber layer thickness (RNFLT),
      macular thickness (MT), and foveal volume (FV) in patients with unilateral
      amblyopia differ between the amblyopic and the sound eye. METHODS: A Humphrey
      Zeiss Stratus (OCT3) with software 4.0.3.1 was used to evaluate 40 patients (17
      male, 23 female; mean age, 15.2 years; range, 5-56 years) with unilateral
      amblyopia. Patients were divided into 2 groups: 20 strabismic and 20
      anisometropic. Maps of macular thickness and RNFL thickness (3.46) created by the
      use of optical coherence tomography were applied to calculate FV and MT and
      RNFLT. RESULTS: Mean best-corrected visual acuity was +0.3 LogMAR (range, +0.2 to
      +1.0) in the amblyopic eye. Mean RNFL thickness was not significantly different
      between eyes in either group. In strabismic amblyopia, mean MT and FV were 5%
      lower in the sound eye than in the amblyopic eye (MT, 267 microm vs 253 microm, p
      = 0.005; FV, 2.57 mm(3) vs 2.43 mm(3), p = 0.001). In anisometropic amblyopia,
      there was no significant difference between eyes in either MT or FV. CONCLUSIONS:
      In patients with strabismic amblyopia, the MT and FV were slightly but
      significantly lower in the sound eye than in the amblyopic eye. The clinical
      importance of this difference is not known. No such difference was observed in
      patients with anisometropic amblyopia.

PMID- 19157940
TI  - Modeling and analysis of MH1 domain of Smads and their interaction with promoter
      DNA sequence motif.
AB  - The Smads are a group of related intracellular proteins critical for transmitting
      the signals to the nucleus from the transforming growth factor-beta (TGF-beta)
      superfamily of proteins at the cell surface. The prototypic members of the Smad
      family, Mad and Sma, were first described in Drosophila and Caenorhabditis
      elegans, respectively. Related proteins in Xenopus, Humans, Mice and Rats were
      subsequently identified, and are now known as Smads. Smad protein family members
      act downstream in the TGF-beta signaling pathway mediating various biological
      processes, including cell growth, differentiation, matrix production, apoptosis
      and development. Smads range from about 400-500 amino acids in length and are
      grouped into the receptor-regulated Smads (R-Smads), the common Smads (Co-Smads)
      and the inhibitory Smads (I-Smads). There are eight Smads in mammals, Smad1/5/8
      (bone morphogenetic protein regulated) and Smad2/3 (TGF-beta/activin regulated)
      are termed R-Smads, Smad4 is denoted as Co-Smad and Smad6/7 are inhibitory Smads.
      A typical Smad consists of a conserved N-terminal Mad Homology 1 (MH1) domain and
      a C-terminal Mad Homology 2 (MH2) domain connected by a proline rich linker. The
      MH1 domain plays key role in DNA recognition and also facilitates the binding of
      Smad4 to the phosphorylated C-terminus of R-Smads to form activated complex. The
      MH2 domain exhibits transcriptional activation properties. In order to understand
      the structural basis of interaction of various Smads with their target proteins
      and the promoter DNA, we modeled MH1 domain of the remaining mammalian Smads
      based on known crystal structures of Smad3-MH1 domain bound to GTCT Smad box DNA
      sequence (1OZJ). We generated a B-DNA structure using average base-pair
      parameters of Twist, Tilt, Roll and base Slide angles. We then modeled
      interaction pose of the MH1 domain of Smad1/5/8 to their corresponding DNA
      sequence motif GCCG. These models provide the structural basis towards
      understanding functional similarities and differences among various Smads.

PMID- 19157941
TI  - N- and C-terminal domains in human holocarboxylase synthetase participate in
      substrate recognition.
AB  - Holocarboxylase synthetase (HCS) catalyzes the binding of the vitamin biotin to
      carboxylases and histones. Carboxylases mediate essential steps in macronutrient
      metabolism. For example, propionyl-CoA carboxylase (PCC) catalyzes the
      carboxylation of propionyl-CoA in the metabolism of odd-chain fatty acids. HCS
      comprises four putative domains, i.e., the N-terminus, the biotin transfer/ATP
      binding domain, a putative linker domain, and the C-terminus. Both N- and C
      termini are essential for biotinylation of carboxylases by HCS, but the exact
      functions of these two domains in enzyme catalysis are unknown. Here we tested
      the hypothesis that N- and C-termini play roles in substrate recognition by HCS.
      Yeast-two-hybrid (Y2H) assays were used to study interactions between the four
      domains of human HCS with p67, a PCC-based polypeptide and HCS substrate. Both N-
      and C-termini interacted with p67 in Y2H assays, whereas the biotin transfer/ATP
      binding and the linker domains did not interact with p67. The essentiality of N-
      and C-termini for interactions with carboxylases was confirmed in rescue
      experiments with mutant Saccharomyces cerevisiae, using constructs of truncated
      human HCS. Finally, a computational biology approach was used to model the 3D
      structure of human HCS and identify amino acid residues that interact with p67.
      In silico predictions were consistent with observations from Y2H assays and yeast
      rescue experiments, and suggested docking of p67 near Arg508 and Ser515 within
      the central domain of HCS.

PMID- 19157942
TI  - A Delphi clinical practice protocol for the management of very long chain acyl
      CoA dehydrogenase deficiency.
AB  - INTRODUCTION: Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is a
      disorder of oxidation of long chain fat, and can present as cardiomyopathy or
      fasting intolerance in the first months to years of life, or as myopathy in later
      childhood to adulthood. Expanded newborn screening has identified a relatively
      high incidence of this disorder (1:31,500), but there is a dearth of evidence
      based outcomes data to guide the development of clinical practice protocols. This
      consensus protocol is intended to assist clinicians in the diagnosis and
      management of screen-positive newborns for VLCAD deficiency until evidence-based
      guidelines are available. METHOD: The Oxford Centre for Evidence-based Medicine
      system was used to grade the literature review and create recommendations graded
      from A (evidence level of randomized clinical trials) to D (expert opinion).
      Delphi was used as the consensus tool. A panel of 14 experts (including
      clinicians, diagnostic laboratory directors and researchers) completed three
      rounds of survey questions and had a face-to-face meeting. RESULT: Panelists
      reviewed the initial evaluation of the screen-positive infant, diagnostic testing
      and management of diagnosed patients. Grade C and D consensus recommendations
      were made in each of these three areas. The panel did not reach consensus on all
      issues, particularly in the dietary management of asymptomatic infants diagnosed
      by newborn screening.

PMID- 19157943
TI  - High frequency of large genomic deletions in the PCCA gene causing propionic
      acidemia.
AB  - Mutations in either the PCCA or PCCB genes are responsible for propionic acidemia
      (PA), one of the most frequent organic acidemias inherited in autosomal recessive
      fashion. Most of the mutations detected to date in both genes are missense. In
      the case of PCCA deficient patients, a high number of alleles remain
      uncharacterized, some of them suspected to carry an exonic deletion. We have now
      employed multiplex ligation probe amplification (MLPA) and long-PCR in some cases
      to screen for genomic rearrangements in the PCCA gene in 20 patients in whom
      standard mutation detection techniques had failed to complete genotype analysis.
      Eight different deletions were found, corresponding to a frequency of 21.3% of
      the total PCCA alleles genotyped at our center. Two of the exonic deletions were
      frequent, one involving exons 3-4 and another exon 23 although in the first case
      two different chromosomal breakpoints were identified. Absence of exons 3 and 4
      which is also the consequence of the novel splicing mutation c.231+1g>c present
      in two patients, presumably results in an in-frame deletion covering 39
      aminoacids, which was expressed in a eukaryotic system confirming its
      pathogenicity. This work describes for the first time the high frequency of large
      genomic deletions in the PCCA gene, which could be due to the characteristics of
      the PCCA gene structure and its abundance in intronic repetitive elements. Our
      data underscore the need of using gene dosage analysis to complement routine
      genetic analysis in PCCA patients.

PMID- 19157944
TI  - Tumor necrosis factor-alpha deficiency retards early fatty-streak lesion by
      influencing the expression of inflammatory factors in apoE-null mice.
AB  - Tumor necrosis factor-alpha (TNF-alpha), a key inflammatory cytokine, plays an
      important role in atherosclerosis. However, its precise characters in primary
      stage of the disease remain unclear. To assess the influence of TNF-alpha on
      inflammatory factors in aorta and liver in apoE and TNF-alpha double mutant (AT)
      mice, a comparative study on early fatty-streak lesion, the mRNA level of target
      gene in aorta and liver of adolescent AT and apoE-null (apoE(-/-)) mice were
      achieved. The characteristics of expression of inflammatory factors, and early
      fatty-streak lesion relevance were analyzed. The plasma cytokines in 6-week-old
      AT and apoE(-/-) mice were also measured. Lipid accumulation in the intima of the
      aorta existed as early as 3 weeks of age in apoE(-/-) mice. Fatty-streak lesion
      was mild in AT mice but prominent in apoE(-/-) mice, at age of 6 weeks.
      Furthermore, most interesting findings indicate that mRNA levels of pro
      atherosclerotic factors, i.e. IL-1beta, IFN-gamma, ICAM-1, VCAM-1, MCP-1, GM-CSF
      and NF-kappaB (p65) were significantly downregulated in AT mice. Whereas IL-2 and
      IkappaB-alpha were upregulated in aorta of AT mice versus those in apoE(-/-) mice
      (p<0.01) and the transcript levels of pro-inflammatory cytokines, such as IL
      1beta, IFN-gamma, ICAM-1, VCAM-1, MCP-1 and GM-CSF, increased with atherogenesis
      progression. On the other hand, the expression of these inflammatory factors in
      the liver displayed somewhat similar fashion to those in the aorta. Moreover, the
      plasma lipids profile in AT mice showed less pro-atherogenic than that of apoE(-/
      ) mice. Our data indicated that TNF-alpha deficiency surely, although not
      completely, retards fatty-streak lesion formation due to downregulated expression
      of the pro-atherosclerotic inflammatory factors in the present circumstance.

PMID- 19157945
TI  - Exogenous mannose does not raise steady state mannose-6-phosphate pools of normal
      or N-glycosylation-deficient human fibroblasts.
AB  - Increasing intracellular mannose-6-phosphate (Man-6-P) was previously reported to
      reduce the amount of the major lipid linked oligosaccharide (LLO) precursor of N
      glycans; a loss that might decrease cellular N-glycosylation. If so, providing
      dietary mannose supplements to glycosylation-deficient patients might further
      impair their glycosylation. To address this question, we studied the effects of
      exogenous mannose on intracellular levels of Man-6-P, LLO, and N-glycosylation in
      human and mouse fibroblasts. Mannose (500microM) did not increase Man-6-P pools
      in human fibroblasts from controls or from patients with Congenital Disorders of
      Glycosylation (CDG), who have 90-95% deficiencies in either phosphomannomutase
      (CDG-Ia) or phosphomannose isomerase (MPI) (CDG-Ib), enzymes that both use Man-6
      P as a substrate. In the extreme case of fibroblasts derived from Mpi null mice
      (<0.001% MPI activity), intracellular Man-6-P levels greatly increased in
      response to exogenous mannose, and this produced a dose-dependent decrease in the
      steady state level of the major LLO precursor. However, LLO loss did not decrease
      total protein N-glycosylation or that of a hypoglycosylation indicator protein,
      DNaseI. These results make it very unlikely that exogenous mannose could impair N
      glycosylation in glycosylation-deficient CDG patients.

PMID- 19157946
TI  - Travel to Syria: expect the unexpected.

PMID- 19157947
TI  - Invasive fungal infections and (1,3)-beta-D-glucan serum concentrations in long
      term intensive care patients.
AB  - OBJECTIVE: Invasive fungal infections are associated with high morbidity and
      increased mortality. This study was performed to assess the epidemiology of
      fungal infections and to determine (1,3)-beta-D-glucan serum concentrations in
      patients admitted to intensive care units (ICUs). PATIENTS AND METHODS: Overall
      197 patients were admitted to nine medical and surgical intensive care units
      (ICUs) at a 2200-bed university hospital during a 3-month period.
      Retrospectively, the patients were split into three groups: group A comprised 24
      patients with proven invasive fungal infections admitted for a median of 40 days.
      Group B comprised 58 patients who were admitted to the ICU for 30 days but
      without fungal infection. One hundred and fifteen post-operative patients served
      as controls (group C). The levels of (1,3)-beta-D-glucan were monitored in all
      patients twice weekly during their ICU admittance. RESULTS: Average (1,3)-beta-D
      glucan concentrations were significantly higher in the patients with fungal
      infections compared to group B and group C (median 44 vs. 22 and 12.9 pg/ml,
      respectively; p<0.001). For a serum (1,3)-beta-D-glucan level of 40 pg/ml, the
      sensitivity, the specificity, the positive predictive value, the negative
      predictive value, the area under the curve of the receiver operating
      characteristics (AUC ROC) curve, the likelihood ratio (LR)+ and LR- were 52.2,
      75.9, 46.2, 80, 0.7, 2.16, and 0.63, respectively, on day 7. Patients in group A
      had bacterial infections significantly more often than patients in group B
      (p=0.003). The hospitalization before ICU admittance for group A was
      significantly longer than for groups B and C (median 19 (group A) vs. 6 (group B)
      vs. 10 (group C) days; p<0.05). CONCLUSIONS: Longer hospitalization and multiple
      bacterial infections were found to be the main risk factors for invasive fungal
      infections. Long-term ICU patients have elevated (1,3)-beta-D-glucan levels, not
      only due to invasive fungal infections, but also due to the serious underlying
      diseases and conditions, inter-current complications, and intensive care
      measures. Yet, persistently high serum levels of (1,3)-beta-D-glucan in ICU
      patients may be indicative of invasive fungal infections and warrant additional
      diagnostic efforts.

PMID- 19157948
TI  - Cryptococcal meningitis in a patient treated with infliximab and mycophenolate
      mofetil for Behcet's disease.

PMID- 19157949
TI  - Schwann cells as putative safe host cells for Leishmania amazonensis.

PMID- 19157950
TI  - [State of the art in chemoradiotherapy combinations and potential role in
      targeting therapy approaches in nonsmall cell lung cancer].
AB  - The preclinical rationale for chemoradiation was demonstrated. While
      chemoradiation allowed for improved outcome in nonsmall cell lung cancer
      patients, prognosis of patients remains particularly pejorative, encouraging
      major expansion of targeted therapies concurrently with radiotherapy. Thorough
      knowledge in biological mechanisms of oncogenesis permitted identifying new
      therapeutic targets, for which specific interactions allow pharmacological
      radiosensitivity modulation. Two modalities of EGFR inhibitors have been
      developed: monoclonal antibodies and tyrosin kinase inhibitors, which assessement
      remains at its beginning. Angiogenesis inhibition was also developed,
      illustrating the absolute necessity for careful clinical assessment. Drugs with
      multiple targets are becoming available and offer new optimization modalities for
      radiation therapy.

PMID- 19157951
TI  - Bilateral knee arthroplasty infection due to Brucella melitensis: a rare
      pathology?

PMID- 19157952
TI  - A simultaneous, direct microwave/ultrasound-assisted digestion procedure for the
      determination of total Kjeldahl nitrogen.
AB  - Simultaneous direct irradiation with microwaves and ultrasound was used to
      determine total Kjeldahl nitrogen. The method involves chemical digestion in two
      steps, mineralization with sulfuric acid and oxidation with H(2)O(2). The most
      influential variables for the microwave/ultrasound (MW/US)-assisted digestion
      were optimized using tryptophan as the model substance. The optimum conditions
      were: H(2)SO(4) volume, 10 mL; H(2)O(2) volume, 5 mL; weight of sample, 0.05 g;
      MW power, 500 W; US power, 50 W; digestion time, 7 min (i.e., 5 min
      mineralization and 2 min oxidation). A modification of the classical Kjeldahl
      (Hach) method and an US-assisted digestion method were used for comparison. The
      latter was also optimized; the optimum conditions were: H(2)SO(4) volume, 10 mL;
      H(2)O(2) volume, 5 mL; sonication time with H(2)SO(4), 15 min; sonication time
      with H(2)O(2),10 min; US power, 50 W; weight of sample, 0.05 g. Five pure amino
      acids and two certified reference materials (NIST standard reference materials
      1547 (peach leaves), and soil, NCS DC 73322) were analyzed to assess the accuracy
      of our new MW/US-assisted digestion method, that was successfully applied to five
      real samples. The significant reduction in digestion time (being 30 min and 25
      min for classical Kjeldahl and US-assisted digestion methods, respectively) and
      consumption of reagents show that simultaneous and direct MW/US irradiation is a
      powerful and promising tool for low-pressure digestion of solid and liquid
      samples.

PMID- 19157953
TI  - Serpentine tongue: A rare manifestation following initiation of levodopa therapy
      in a patient with Parkinson's disease.

PMID- 19157954
TI  - A model of deformable rings for interpretation of wireless capsule endoscopic
      videos.
AB  - Wireless Capsule Endoscopy (WCE) provides a means to obtain a detailed video of
      the small intestine. A single session with WCE may produce nearly 8h of video.
      Its interpretation is tedious task, which requires considerable expertise and is
      very stressful. The Model of Deformable Rings (MDR) was developed to preprocess
      WCE video and aid clinicians with its interpretation. The MDR uses a simplified
      model of a capsule's motion to flexibly match (register) consecutive video
      frames. Essentially, it computes motion-descriptive characteristics and produces
      a two-dimensional representation of the gastrointestinal (GI) tract's internal
      surface - a map. The motion-descriptive characteristics are used to indicate
      video fragments which exhibit segmentary contractions, peristalsis, refraction
      phases and areas of capsule retention. Within maps, certain characteristics that
      indicate areas of bleeding, ulceration and obscuring froth could be recognized.
      Therefore, the maps allow quick identification of such abnormal areas. The
      experimental results demonstrate that the number of discovered pathologies and
      gastrointestinal landmarks increases with the MDR technique.

PMID- 19157955
TI  - Antitumor activity of suberoylanilide hydroxamic acid against human oral squamous
      cell carcinoma cell lines in vitro and in vivo.
AB  - It has been reported recently that histone deacetylase inhibitors (HDACIs) can
      block the growth of a variety of malignant tumor cells by reversing the silencing
      of the tumor suppressor genes; these will be the anticancer agents of the next
      generation. In this study, we evaluated the antitumor effects of the HDACI
      suberoylanilide hydroxamic acid (SAHA) on oral squamous cell carcinoma (OSCC) and
      investigated its molecular mechanism. SAHA suppressed the in vitro proliferation
      of OSCC cell lines in a dose- and time-dependent manner. Flow cytometric analyses
      showed that treatment with SAHA led to G1 phase cell-cycle arrest of OSCC cells,
      accompanying a decrease in the percentage of S-phase cells. Western blot analyses
      demonstrated that the expression of p21 protein was remarkably augmented and
      hyperacetylation of p53 was induced after SAHA treatment. These results suggest
      that administration of SAHA suppresses OSCC growth through G1 phase arrest.
      Additionally, we observed that the growth of xenograft SAS tumors in nude mice
      was significantly blocked by the administration of SAHA without major adverse
      effects.

PMID- 19157956
TI  - Genetic and genomic dissection of maize root development and architecture.
AB  - The complex architecture and plasticity of the maize root system is controlled by
      a plethora of genes. Mutant analyses have identified genes regulating shoot-borne
      root initiation (RTCS) and root hair elongation (RTH1 and RTH3). Quantitative
      trait locus (QTL) studies have highlighted the importance of seminal roots,
      lateral roots, and root hairs in phosphorus acquisition. Additionally, QTLs that
      influence root features were shown to affect yield under different water regimes
      and under flooding conditions. Finally, proteome and transcriptome analyses
      provided insights into maize root development and identified candidate genes
      associated with cell specification, and lateral root initiation in pericycle
      cells. The targeted application of forward-genetics and reverse-genetics
      approaches will accelerate the unraveling of the functional basis of root
      development and architecture.

PMID- 19157957
TI  - Next is now: new technologies for sequencing of genomes, transcriptomes, and
      beyond.
AB  - The sudden availability of DNA sequencing technologies that rapidly produce vast
      amounts of sequence information has triggered a paradigm shift in genomics,
      enabling massively parallel surveying of complex nucleic acid populations. The
      diversity of applications to which these technologies have already been applied
      demonstrates the immense range of cellular processes and properties that can now
      be studied at the single-base resolution. These include genome resequencing and
      polymorphism discovery, mutation mapping, DNA methylation, histone modifications,
      transcriptome sequencing, gene discovery, alternative splicing identification,
      small RNA profiling, DNA-protein, and possibly even protein-protein interactions.
      Thus, these deep sequencing technologies offer plant biologists unprecedented
      opportunities to increase the understanding of the functions and dynamics of
      plant cells and populations.

PMID- 19157958
TI  - Orphan legume crops enter the genomics era!
AB  - Many of the world's most important food legumes are grown in arid and semi-arid
      regions of Africa and Asia, where crop productivity is hampered by biotic and
      abiotic stresses. Until recently, these crops have also suffered from a dearth of
      genomic and molecular-genetic resources and thus were 'orphans' of the genome
      revolution. However, the community of legume researchers has begun a concerted
      effort to change this situation. The driving force is a series of international
      collaborations that benefit from recent advances in genome sequencing and
      genotyping technologies. The focus of these activities is the development of
      genome-scale data sets that can be used in high-throughput approaches to
      facilitate genomics-assisted breeding in these legumes.

PMID- 19157960
TI  - Shigella type III secretion effectors: how, where, when, for what purposes?
AB  - Bacteria of Shigella spp., the causative agents of shigellosis in humans, possess
      a repertoire of approximately 25-30 effectors injected into host cells by a type
      III secretion apparatus (T3SA). The T3SA activity is activated upon contact of
      bacteria with cells and controls expression of some effectors. Recent structural
      and functional studies suggest that two different sets of effectors are involved
      in inducing actin cytoskeleton reorganization to promote entry of bacteria into
      epithelial cells and in modulating cell signaling pathways to dampen innate
      immune responses induced upon infection, respectively. Schematically, effectors
      involved in entry are produced independently of the T3SA activity, whereas
      effectors involved in controlling the cell responses are produced upon activation
      of the T3SA.

PMID- 19157959
TI  - Salmonella takes control: effector-driven manipulation of the host.
AB  - Salmonella pathogenesis relies upon the delivery of over thirty specialised
      effector proteins into the host cell via two distinct type III secretion systems.
      These effectors act in concert to subvert the host cell cytoskeleton, signal
      transduction pathways, membrane trafficking and pro-inflammatory responses. This
      allows Salmonella to invade non-phagocytic epithelial cells, establish and
      maintain an intracellular replicative niche and, in some cases, disseminate to
      cause systemic disease. This review focuses on the actions of the effectors on
      their host cell targets during each stage of Salmonella infection.

PMID- 19157962
TI  - Growth, structural, spectroscopic and optical studies of pure and amino acid
      (glycine) doped methyl-para-hydroxy benzoate single crystals.
AB  - Methyl-para-hydroxy benzoate is a potential organic nonlinear optical (NLO)
      material. The pure and amino acid (glycine) doped MHB crystals are grown by slow
      evaporation solution growth technique. Single crystal X-ray diffraction studies
      of both pure and amino acid doped samples are carried out and the results are
      compared. FTIR studies are performed to identify the presence of various
      functional groups in the grown crystal. The UV-vis spectra confirm the
      improvement in the transparency of these crystals on doping amino acid. The amino
      acid doping improves the NLO properties. The dopant increases the hardness value
      of the material.

PMID- 19157961
TI  - Legionella pneumophila Dot/Icm translocated substrates: a sum of parts.
AB  - Legionella pneumophila is an intracellular pathogen of freshwater amoeba and of
      alveolar macrophages in human hosts. After phagocytosis, L. pneumophila
      establishes a unique intracellular vacuolar niche that avoids entry into the
      lysosomal network. Critical for L. pneumophila intracellular growth is the
      Dot/Icm type IVB translocation system. Although over 80 substrates of the Dot/Icm
      apparatus have been identified, individual substrates are often genetically
      redundant, complicating their analysis. Deletion of critical Dot/Icm
      translocation system components causes a variety of defects during intracellular
      growth. Many of these effects on the host cell likely result from the actions of
      one or more Dot/Icm translocated substrates. Loss of single substrates never
      generates the profound effects observed in strains lacking translocation system
      components.

PMID- 19157963
TI  - Effect of electron beam irradiation on the structural properties of PVA/V(2)O(5)
      xerogel.
AB  - Poly(vinylalcohol) (PVA)/vanadium pentoxide xerogel (VXG) composites were
      prepared and exposed to different electron beam irradiation doses. Changes in the
      structural properties, crystallinity degree of composites with increasing
      irradiation doses and VXG content were subsequently investigated using the
      Fourier transformer infrared spectroscopy (FTIR), X-ray diffraction (XRD), and
      differential scanning calorimetry (DSC) techniques. The crystallinity degree of
      the PVA matrix was found to decrease markedly due to VXG addition and/or
      irradiation process.

PMID- 19157964
TI  - Growth and spectroscopic characterization of a new organic nonlinear optical
      crystal: L-alaninium succinate.
AB  - A novel organic nonlinear optical (NLO) material, l-alaninium succinate, was
      synthesized by the standard method. The synthesized material was purified by
      repeated recrystallization. Single crystals were grown by slow evaporation
      technique using water as solvent. The grown crystals were characterized by FT-IR,
      FT-NMR and UV-vis-NIR techniques. The second harmonic generation (SHG) from the
      material was confirmed using Nd:YAG laser which shows that LAS has 23% SHG
      efficiency of that of the standard KDP. The UV-vis-NIR transmittance was recorded
      in the range from 190 to 1100nm. In this study, the lower cut-off is shifted
      towards UV region (190nm) which shows that LAS has good transmittance in region
      from 190 to 1100nm and it makes LAS for SHG. Functional groups present in the
      grown crystal were identified using FT-IR spectrum which gives confirmation of
      NH(3)(+) ion in LAS. The chemical structure of l-alaninium succinate was
      established by FT-NMR technique.

PMID- 19157965
TI  - Fluorescence-based sensor for Pb(II) using tetra-(3-bromo-4
      hydroxyphenyl)porphyrin in liquid and immobilized medium.
AB  - A new optical sensor for sensing of Pb(2+) in immobilized medium (PVC film) and
      ethanol medium was developed by using 5,10,15,20-tetra-(3-bromo-4
      hydroxyphenyl)porphyrin (TBHPP) synthesized. The sensor-based TBHPP showed a
      linear response towards Pb(2+) in concentration range from 5x10(-6) to 4x10(
      4)molL(-1) in PVC film and 5x10(-6) to 3x10(-4)molL(-1) in ethanol medium, with a
      working pH 7. The detection limit was 2x10(-8) and 4x10(-8)molL(-1) for Pb(2+) in
      PVC film and ethanol medium respectively. The response time of Pb(2+) was found
      as 4min for PVC film and 2min for ethanol medium. The sensor developed in two
      different mediums was used for lead determination in standard soil sample with
      satisfactory results.

PMID- 19157966
TI  - The realities of implementation of Clinical Context Object Workgroup (CCOW)
      standards for integration of vendor disparate clinical software in a large
      medical center.
AB  - CCOW standards have been touted to currently be the best way to integrate
      disparate clinical applications by passing user identification and passwords as
      well as patient context between these applications at the desktop. However,
      nothing has been published in academic journals on the actual realities of
      implementation of CCOW. In this report, we describe the implementation of CCOW
      for our three main clinical applications and compare this with the simultaneous
      development and implementation of a portal session manager for the same purpose.
      We found the portal session manager much easier to develop and implement than
      CCOW. The resulting functionality was almost equivalent as judged by our clinical
      end users who compared both solutions. We now have the portal session manager
      functional across the institution and have stopped any further work on CCOW.

PMID- 19157967
TI  - Handheld computers for survey and trial data collection in resource-poor
      settings: development and evaluation of PDACT, a Palm Pilot interviewing system.
AB  - OBJECTIVE: Handheld computers (personal digital assistant, PDA) have the
      potential to reduce the logistic burden, cost, and error rate of paper-based
      health research data collection, but there is a lack of appropriate software. The
      present work describes the development and evaluation of PDACT, a Personal Data
      Collection Toolset (www.healthware.org/pdact/index.htm) for the Palm Pilot
      handheld computer for interviewer-administered and respondent-administered data
      collection. METHODS: We developed Personal Data Collection Toolkit (PDACT)
      software to enable questionnaires developed in QDS Design Studio, a Windows
      application, to be compiled and completed on Palm Pilot devices and evaluated in
      several representative field survey settings. RESULTS: The software has been used
      in seven separate studies and in over 90,000 interviews. Five interviewer
      administered studies were completed in rural settings with poor communications
      infrastructure, following one day of interviewer training. Two respondent
      administered questionnaire studies were completed by learners, in urban secondary
      schools, after 15min training. Questionnaires were available on each handheld in
      up to 11 languages, ranged from 20 to 580 questions, and took between 15 and
      90min to complete. Up to 200 Palm Pilot devices were in use on a single day and,
      in about 50 device-years of use, very few technical problems were found. Compared
      with paper-based collection, data validation and cleaning times were reduced, and
      fewer errors were found. PDA data collection is easy to use and preferred by
      interviewers and respondents (both respondent-administered and interviewer
      administered) over paper. Data are compiled and available within hours of
      collection facilitating data quality assurance. Although hardware increases the
      setup cost of the first study, the cumulative cost falls thereafter, and
      converges on the cumulative cost of paper-based studies (four, in the case of our
      interviewer-administered studies). Handheld data collection is an appropriate,
      affordable and convenient technology for health data collection, in diverse
      settings.

PMID- 19157968
TI  - The OpenMRS Implementers Network.
AB  - OBJECTIVE: OpenMRS (www.openmrs.org) is a configurable open source electronic
      medical record application developed and maintained by a large network of open
      source developers coordinated by the Regenstrief Institute and Partners in Health
      and mainly used for HIV patient and treatment information management in Africa.
      Our objective is to develop an open Implementers Network for OpenMRS to provide
      regional support for the growing number of OpenMRS implementations in Africa and
      to include African developers and implementers in the future growth of OpenMRS.
      METHODS: We have developed the OpenMRS Implementers Network using a dedicated
      Wiki site and e-mail server. We have also organized annual meetings in South
      Africa and regional training courses at African locations where OpenMRS is being
      implemented. An OpenMRS Internship program has been initiated and we have started
      collaborating with similar networks and projects working in Africa. To evaluate
      its potential, OpenMRS was implemented initially at one site in South Africa by a
      single implementer using a downloadable OpenMRS application and only the OpenMRS
      Implementers Network for support. RESULTS: The OpenMRS Implementers Network Wiki
      and list server have grown into effective means of providing implementation
      support and forums for exchange of implementation experiences. The annual OpenMRS
      Implementers meeting has been held in South Africa for the past three years and
      is attracting successively larger numbers of participants with almost 200
      implementers and developers attending the 2008 meeting in Durban, South Africa.
      Six African developers are presently registered on the first intake of the
      OpenMRS Internship program. Successful collaborations have been started with
      several African developer groups and projects initiated to develop
      interoperability between OpenMRS and various applications. The South African
      OpenMRS Implementer group successfully configured, installed and maintained an
      integrated HIV/TB OpenMRS application without significant programming support.
      Since then, this model has been replicated in several other African sites. The
      OpenMRS Implementers Network has contributed substantially to the growth and
      sustainability of OpenMRS in Africa and has become a useful way of including
      Africans in the development and implementation of OpenMRS in developing
      countries. The Network provides valuable support and enables a basic OpenMRS
      application to be implemented in the absence of onsite programmers.

PMID- 19157969
TI  - Vision and challenges of Evidence-Based Health Informatics: a case study of a
      CPOE meta-analysis.
AB  - OBJECTIVE: To discuss, taking the example of a meta-analysis on computerized
      physician order entry (CPOE) systems, the special challenges of Evidence-Based
      Health Informatics, defined as the conscientious, explicit and judicious use of
      current best evidence when making decisions about introduction and operation of
      information technology in a given health care setting. METHODS: We conducted a
      case study by performing a systematic review and meta-analysis of CPOE studies.
      We collected and discussed the challenges we addressed and how they could be
      overcome. RESULTS: Challenges comprise the correct identification of published
      health informatics evaluation studies, the low reporting and study quality of
      studies, the problem of combining evidence from heterogeneous studies, and the
      problem of publication bias in health informatics. CONCLUSION: Based on our
      experiences while conducting the CPOE meta-analysis, we argue that we are still
      at the beginning of Evidence-Based Health Informatics. To overcome the discussed
      challenges, health informatics should strive for harmonized terminology, a study
      registry, reporting standards, financial or legal incentives for conducting
      studies, methods to combine evidence from quantitative and qualitative studies,
      and guidelines for conducting and publishing evaluation studies.

PMID- 19157970
TI  - Detection of WU polyomavirus DNA by real-time PCR in nasopharyngeal aspirates,
      serum, and stool samples.
AB  - BACKGROUND: The human WU polyomavirus (WUPyV) has been recently described as a
      novel virus in respiratory tract samples. OBJECTIVE: To investigate the viral
      load of WUPyV in nasopharyngeal aspirates (NPAs), stool, and serum samples of
      pediatric patients with acute respiratory tract diseases. STUDY DESIGN: We
      established a real-time PCR for WUPyV DNA and tested NPA obtained between 2002
      and 2007 from pediatric in-patients with acute respiratory tract diseases. In
      addition, 14 stool and 14 serum samples of children with WUPyV DNA positive NPA
      were analysed. RESULTS: WUPyV DNA was found in 5.2% of 1232 NPA. The median viral
      load in the NPA was 950 copies/ml (maximum 3.4 x 10(10) copies/ml). The WUPyV
      load in NPA was neither associated with the coinfection status nor with the
      clinical diagnoses. WUPyV DNA was found in 3 of 14 serum samples and in 2 of 14
      stool samples. The WUPyV load in NPA tended to be higher in viremic children.
      CONCLUSION: WUPyV DNA was found in NPA, serum, and stool of hospitalised children
      with acute respiratory tract diseases. Further studies are necessary to determine
      whether WUPyV is a human pathogen.

PMID- 19157971
TI  - Emergence of oseltamivir-resistant influenza A/H3N2 virus with altered
      hemagglutination pattern in a hematopoietic stem cell transplant recipient.
AB  - BACKGROUND: Persistent influenza virus replication during antiviral therapy in
      patients undergoing hematopoietic stem cell transplantation (HSCT) could promote
      the emergence of antiviral drug resistance. OBJECTIVES: To follow the viral
      genotypic and drug susceptibility changes in a patient who developed progressive
      influenza A/H3N2 pneumonia despite oseltamivir therapy after haploidentical HSCT.
      STUDY DESIGN: Direct genotypic analysis of the neuraminidase (NA) and
      hemagglutinin (HA) genes in successive bronchoalveolar lavage specimens was
      employed in combination with hemagglutination and NA enzymatic activity assays of
      the corresponding viral isolates. RESULTS: The emergence of NA oseltamivir
      resistance mutation R292K was detected by 12 days of oseltamivir treatment with
      44,286-fold increase in oseltamivir IC50. Resurgence of wild type viral
      population was identified by 7 days after cessation of oseltamivir. Sequential HA
      mutations R228S and A138S were identified and associated with a shift in the HA
      receptor binding pattern reflected by loss of the ability to agglutinate chicken
      erythrocytes. CONCLUSIONS: These rapid evolutionary changes warrant close
      virologic monitoring of immunocompromised patients treated for influenza
      infection, and raise concern about the efficacy of mono-drug therapy for
      influenza-associated disease in HSCT recipients.

PMID- 19157972
TI  - The effect of controlled therapy interruption in chronic HCV infection: enhanced
      host immune response? A hypothesis.
AB  - BACKGROUND: We have hypothesized that prolonged viral suppression partially
      reverses immune tolerance in chronic hepatitis C virus infection. Brief periods
      of treatment interruption can then simulate 'auto-vaccination' and evoke powerful
      secondary host immune responses. OBJECTIVE: To determine the effect of controlled
      therapy interruption CTI on viral load in previous relapsers to interferon and
      ribavirin treatment. STUDY DESIGN: Virus is maintained at undetectable levels for
      2-8 weeks with pegylated interferon and ribavirin and then briefly interrupted,
      restarting as soon as viremia returns (cycle 1). It is suppressed for at least a
      further 4 weeks, then briefly interrupted again (cycle 2). RESULTS: Viremia
      relapsed within 2-4 weeks (time to relapse TTR) after the first treatment
      interruption in all four patients in cycle 1. TTR increased sevenfold with the
      second treatment interruption in patient 1 and was followed by sustained
      virological response with cycle 3. In patient 2, TTR increased threefold after
      cycle 2 and subsequent cycles. Serum ALT and bilirubin rose significantly with
      treatment interruption during cycles 2 and 3, returning to baseline with
      treatment resumption. Serum bilirubin rose to 12.3mg/dl when two doses of
      pegylated interferon were missed during cycle 4. In patients 3 and 4, TTR was
      unchanged after three consecutive cycles. However, VL has remained more than 1
      log below baseline for up to 18 months in both. CONCLUSIONS: These observations
      suggest that CTI exerts significant control of chronic hepatitis C viremia.

PMID- 19157973
TI  - The occipital alpha rhythm related to the "migraine cycle" and headache burden: a
      blinded, controlled longitudinal study.
AB  - OBJECTIVE: Neurophysiological studies have shown a fluctuating neural dysfunction
      in migraine. This pathophysiological feature has not previously been investigated
      by quantitative electroencephalography (QEEG). The alpha rhythm is especially
      interesting, because it is influenced by ischemia and neuronal dysfunction within
      the posterior circulation area. METHODS: We investigated alpha peak frequency,
      variability, peak power and asymmetry in 41 migraineurs and 32 controls.
      Electroencephalography (EEG) was recorded on three random days and
      retrospectively classified as preattack, attack, postattack or interictal, based
      on the patient's headache diaries. We also searched for correlations between
      alpha rhythm parameters and disease duration, attack duration, attack frequency,
      pain intensity and photophobia. RESULTS: Peak frequency reduction correlated with
      increasing disease- and attack duration. Frequency variability increased before
      the attack, while peak power increased during the attack. Alpha peak width, peak
      frequency and peak power were similar for migraineurs and controls in the
      interictal period. CONCLUSION: The accumulated burden of migraine caused slight
      alterations in the physiology of the visual cortex. Small alpha rhythm changes
      were observed along the migraine cycle. SIGNIFICANCE: This is a longitudinal,
      controlled study. It is the first to report changes in alpha rhythm with
      increased migraine load, even when the QEEG is not influenced by recent or
      imminent attacks.

PMID- 19157974
TI  - Motivated and controlled attention to emotion: time-course of the late positive
      potential.
AB  - OBJECTIVE: The present study examined the time-course of automatic and controlled
      modulation of the late positive potential (LPP) during emotional picture viewing.
      METHODS: Participants (N=32) viewed neutral and unpleasant stimuli for 6000 ms;
      at 3000 ms, one of two tones signaled participants to attend either to a more or
      less arousing portion of the picture. The time-course of the LPP was examined
      both during the passive viewing and directed attention portions of the trial
      using the method proposed by Guthrie and Buchwald [Guthrie D, Buchwald JS.
      Significance testing of difference potentials. Psychophysiology 1991;28(2):240
      4]. RESULTS: During passive viewing, the LPP became reliably larger following the
      presentation of unpleasant pictures from 160 ms onward; the magnitude of the LPP
      became reliably smaller beginning 620 ms after participants were instructed to
      attend to the less arousing aspects of unpleasant pictures - and this difference
      was maintained throughout the duration of the trial. CONCLUSIONS: The LPP
      reflects relatively automatic attention to emotional visual stimuli, but is also
      sensitive to manipulations of directed attention toward arousing versus neutral
      aspects of such stimuli. SIGNIFICANCE: These results shed further light on the
      time-course of emotional and cognitive modulation of the LPP, and suggest that
      the LPP reflects the relatively rapid and dynamic allocation of increased
      attention to emotional stimuli.

PMID- 19157975
TI  - RLS and blood donation.
AB  - BACKGROUND AND PURPOSE: The link between brain iron deficiency and RLS is now
      well established. In a related observation, several conditions that can deplete
      iron stores have been linked to increased probability of RLS. Blood donation has
      been linked to iron deficiency. It has thus been hypothesized that donating blood
      may be a risk factor for developing RLS. PATIENTS AND METHODS: Two thousand and
      five UK blood donors, ranging from first-time donors to some who had donated more
      than 70 times, completed the validated Cambridge-Hopkins RLS questionnaire (CH
      RLSq) following their donation session. The questionnaire included a set of
      questions designed to diagnose RLS. The donors' histories of blood donations were
      determined both from self-report and from the National Blood Service database.
      RESULTS: A number of statistical models were constructed to determine whether the
      probability of RLS diagnosis was related to the history of blood donations.
      Controlling for age and sex, no evidence was found to suggest that a greater
      number or frequency of blood donations increased the risk of RLS. Even amongst
      sub-groups especially vulnerable to iron depletion through blood donation, such
      as vegetarians or low weight individuals, no evidence for an increased risk of
      RLS could be found. CONCLUSIONS: We found no evidence that the frequency or
      number of blood donations up to the UK maximum of three times a year would
      increase the risk of RLS.

PMID- 19157976
TI  - Escherichia coli encoding Shiga toxin 2f as an emerging human pathogen.
AB  - Escherichia coli harbouring the stx2f gene have been previously reported in
      pigeons. Here we demonstrate the presence of this allele in human diarrhoeagenic
      E. coli strains originally classified as atypical enteropathogenic E. coli
      (aEPEC). Thirty-two stx2f-positive E. coli serotyped as O63:H6, O128:H2,
      O132:H34, O145:H34, and O178:H7 were found to belong to a large number of clonal
      groups due to their different MLST-, PFGE- and virulence patterns. The appearance
      of various stx2f-positive clonal lineages among E. coli reveals emerging clinical
      significance. Therefore, it seems to be prudent to include stx2f into the
      diagnostic scope employed for laboratory investigation of enteric infections.

PMID- 19157977
TI  - Induction of a protective response with an IgA monoclonal antibody against
      Mycobacterium tuberculosis 16kDa protein in a model of progressive pulmonary
      infection.
AB  - Mycobacterium tuberculosis is a facultative intracellular pathogen for which cell
      mediated immunity is considered the major component of the immune response. For
      many decades, the prevailing scientific view has been the antibodies have little
      or no role in modifying the course of M. tuberculosis infection. In recent years,
      several studies have challenged this dogma, and there is a body of evidence that
      supports a role of antibodies against M. tuberculosis. In the present work, we
      evaluated the protective activity of two monoclonal antibodies (TBA61 and TBA84).
      Here, we chose the intratracheal model of pulmonary infection to evaluate
      bacterial load and morphometric and histological changes in the lungs of treated
      mice. Data obtained revealed the reduction of bacterial load and milder
      morphometric and histopathological changes in mice treated with TBA61 at 21 days
      post-infection with M. tuberculosis H37Rv compared to those treated with TBA84
      and control mice. These results allow continuing exploring the potential use of
      monoclonal antibodies as prophylactic and therapeutic agents against
      intracellular pathogens such as M. tuberculosis.

PMID- 19157978
TI  - Determinants of elevated NT-proBNP levels in patients with hypertrophic
      cardiomyopathy: an echocardiographic study.
AB  - BACKGROUND: The purpose of this study was to explore the relationship between
      plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and extensive
      echocardiographic variables in patients with hypertrophic cardiomyopathy (HCM).
      METHODS: We evaluated plasma NT-proBNP levels in 88 patients with HCM and
      examined the plasma NT-proBNP levels' relationships with echocardiographic
      indexes. Echocardiographic variables were analysed using univariate and
      multivariate logistic regression to identify predictors of NT-proBNP elevation.
      RESULTS: Several echocardiographic variables predicted NT-proBNP elevation,
      including left atrial dimension index (LADI), left ventricular maximal wall
      thickness (MWT), left ventricular posterior wall thickness, severe mitral
      regurgitation, mitral septal and lateral tissue Doppler velocities, and mitral
      septal E/Ea ratio. Left ventricular ejection fraction, left ventricular
      dimensions, mitral early flow propagation velocity, isovolumic relaxation time,
      and left ventricular outflow tract obstruction were not significant predictors of
      NT-proBNP in this group of patients. With multivariate analysis LADI (HR 5.0; 95%
      CI 1.5-17.1, p=0.01) and MWT (HR 4.0; 95% CI 1.2-13.2, p=0.022) emerged as
      independent determinants of NT-proBNP elevation. CONCLUSIONS: In HCM plasma NT
      proBNP is prominently increased. LADI and MWT are independent predictors of
      elevated levels. These data indicate that NT-proBNP elevations are mainly
      determined by diastolic load in HCM.

PMID- 19157979
TI  - Targeting vascular calcification: softening-up a hard target.
AB  - Widespread vascular calcification is a ubiquitous feature of aging and is
      prevalent in association with a number of common pathologies including
      atherosclerosis, renal failure, and diabetes. Once thought of as innocuous,
      emerging evidence suggests that calcification is causal in precipitating vascular
      events and mediating chronic cardiovascular damage, independent of disease
      context. Importantly, a large body of data has shed light on the factors that
      favor the formation of calcification in vivo, as well as on the complex
      mechanisms that initiate and promote it. This has identified some novel targets
      and allowed for the possibility that calcification can potentially be blocked and
      ultimately regressed. Targets include local and circulating inhibitors of
      calcification as well as factors that may ameliorate vascular smooth muscle cell
      (VSMC) apoptosis. Despite this, the vasculature remains a difficult tissue to
      target and currently there are no effective treatments in general use. More
      crucially, any potential treatments will need to be carefully evaluated as they
      may impinge on bone metabolism. Our best hope for the near future is to normalize
      factors associated with accelerated calcification in pathologies such as renal
      failure where, aberrant mineral metabolism, as well as treatment regimes, may
      contribute to the initiation and progression of calcification.

PMID- 19157980
TI  - CGRP receptors in the control of pain and inflammation.
AB  - Calcitonin gene related peptide (CGRP) has been proposed to contribute to pain
      transmission and inflammation and for these reasons to the mechanism of migraine.
      CGRP is, in fact, expressed in and released from a subset of polymodal primary
      sensory neurons of the trigeminal ganglion. Release of CGRP in the dorsal spinal
      cord has been associated to nociceptive transmission, and release from
      perivascular nerve endings causes neurogenic vasodilatation. CGRP levels increase
      in the cranial circulation during migraine attacks, and GRP injection in
      migraineurs results in migraine-like attacks. Most importantly, two chemically
      unrelated CGRP-receptor antagonists, the parenteral agent, olcegepant, and the
      orally available telcagepant demonstrated efficacy in the treatment of migraine
      attacks, thus supporting CGRP as an important mediator in migraine.

PMID- 19157981
TI  - Possible new druggable targets for the treatment of nephrosis. Perhaps we should
      find them in caveolea?
AB  - Nephrosis refers to a condition resulting from proteinuric kidney disease,
      leading to irreversible renal parenchymal damage and end-stage renal disease when
      left untreated. Furthermore, nephrosis appears to be a communicable disease
      carrying risks and complications to other organs such as the heart. Key
      pathophysiolgical processes involved in initiating and progressing renal damage
      in nephrosis and its complications may include altered glomerular hemodynamics
      after initial renal damage and loss of nephrons, nephrotoxicity of increased
      renal protein traffic enforcing intrinsic 'common pathway' mechanisms of renal
      scarring, and generalized endothelial dysfunction proceeding CV disease. The
      reader is first provided a basic overview on key mechanisms, targets and
      therapies in nephrosis while referred to some excellent updates hereon for more
      detailed information. The broader purpose of this short review, however, is to
      highlight caveolae/caveolins and caveolar function as central modulators in all
      the above key processes of nephrosis. Caveolae - little caves in the plasma
      membrane that are particularly abundant in endothelial cells, amongst others -
      are now known to be involved not only in endothelial transcytosis (e.g. of
      albumin) but also in cholesterol homeostasis (LDL-transport) and, importantly, in
      signal transduction such as insulin signalling and nitric oxide signalling in
      endothelial function and regulation of vasomotor tone, as well as signalling by
      growth factor receptors - such as TGF-beta - which may participate in renal
      scarring. It is suggested that caveolae may represent crucial sites where
      possible new druggable targets in nephrosis may be found.

PMID- 19157982
TI  - SSRIs act as selective brain steroidogenic stimulants (SBSSs) at low doses that
      are inactive on 5-HT reuptake.
AB  - Brain principal glutamatergic neurons synthesize 3alpha-hydroxy-5alpha-pregnan-20
      one (Allo), a neurosteroid that potently, positively, and allosterically
      modulates GABA action at GABA(A) receptors. Cerebrospinal fluid (CSF) Allo levels
      are decreased in patients with posttraumatic stress disorder (PTSD) and major
      depression. This decrease is corrected by fluoxetine in doses that improve
      depressive symptoms. Emotional-like behavioral dysfunctions (aggression, fear,
      and anxiety) associated with a decrease of cortico-limbic Allo content can be
      induced in mice by social isolation. In socially isolated mice, fluoxetine and
      analogs stereospecifically normalize the decrease of Allo biosynthesis and
      improve behavioral dysfunctions by a mechanism independent from 5-HT reuptake
      inhibition. Thus, fluoxetine and related congeners facilitate GABA(A) receptor
      neurotransmission and effectively ameliorate emotional and anxiety disorders and
      depression by acting as selective brain steroidogenic stimulants (SBSSs).

PMID- 19157983
TI  - Endocannabinoid signals in the control of emotion.
AB  - The appropriate control of emotional responses evoked by environmental stimuli is
      an important innate mechanism for ensuring quality of life and even for survival.
      Inappropriate responses and decreased abilities to adjust to changed
      environmental situations can lead to psychiatric disorders, such as posttraumatic
      stress disorders, phobia and depression. Endocannabinoid signalling has emerged
      as one of the regulatory systems of the brain supporting appropriate emotional
      responses. As various components of the endocannabinoid system have become
      therapeutic targets, understanding the endocannabinoids' mechanism of action is
      an important research topic for a rationalized drug design and optimal
      therapeutic strategies.

PMID- 19157984
TI  - Targeting the redox sensitive Nrf2-Keap1 defense pathway in cardiovascular
      disease: protection afforded by dietary isoflavones.
AB  - Cells have evolved highly regulated defense systems, including the redox
      sensitive Nrf2-Keap1 signaling pathway involved in the transcriptional activation
      of phase II defense and antioxidant genes in oxidative stress. Increased
      generation of reactive oxygen species (ROS) in cardiovascular disease (CVD) leads
      to impaired endothelial function and reduced nitric oxide (NO) bioavailability.
      Although epidemiological evidence suggests that diets containing plant-derived
      isoflavones (phytoestrogens) afford protection against CVDs, supplementation
      trials have largely reported only marginal health benefits. The molecular
      mechanisms by which soy isoflavones (genistein, daidzein, and equol) afford
      protection against oxidative stress in CVD remain to be investigated in large
      scale clinical trials. Studies in animal models and cultured vascular cells have
      established that isoflavones increase eNOS activity and expression and activate
      the Nrf2-Keap1 signaling pathway, leading to an upregulation of detoxifying and
      antioxidant defense genes. We review recent advances in the understanding of the
      signal transduction pathways involved in the activation of endothelial NO
      production and Nrf2-Keap1-mediated antioxidant gene expression by dietary
      isoflavones.

PMID- 19157985
TI  - Peripheral mechanisms of opioid analgesia.
AB  - Potent and clinically significant analgesic effects can be brought about by
      opioids acting outside the central nervous system. Injury and inflammation of
      peripheral tissues leads to increased synthesis, axonal transport, membrane
      directed trafficking and G-protein coupling of opioid receptors in dorsal root
      ganglion neurons. These events are dependent on neuronal electrical activity,
      cytokines and nerve growth factor and lead to an enhanced analgesic efficacy of
      peripherally active opioids. Leukocytes infiltrating inflamed tissue upregulate
      signal-sequence-encoding mRNA for beta-endorphin and its processing enzymes.
      Depending on the cell type and stimulus, the opioid release is contingent on
      extracellular Ca2+ or on release of Ca2+ from endoplasmic reticulum. Analgesia
      results from inhibition of sensory neuron excitability and of proinflammatory
      neuropeptide release.

PMID- 19157986
TI  - Glutamate and reinstatement.
AB  - The importance of glutamate in the reinstatement of cocaine-seeking behavior has
      been established. New molecular and neurochemical adaptations in the
      glutamatergic system which drive cocaine relapse have been identified, such as
      the ability of CB1 receptor stimulation to reduce basal glutamate levels and the
      involvement of the GluR1 receptor subunit in reinstatement. Furthermore, it is
      apparent that similar glutamatergic neuroadaptations arise after self
      administration of cocaine, heroin, nicotine, and alcohol. For example,
      reinstatement to cocaine, nicotine, and alcohol can be prevented both by the
      stimulation of group II mGluR receptors and by the blockade of group I mGluR
      receptors. The similarities in the neurochemistry behind relapse to these varied
      drug classes indicate that drugs that target the glutamate system could be
      effective at treating relapse to multiple types of drugs.

PMID- 19157987
TI  - Roles of prostaglandin E receptors in stress responses.
AB  - Stress is a condition in which the body homeostasis is perturbed by various
      stimuli such as sickness and psychological stimuli. Stress evokes adaptive
      responses including febrile, neuroendocrine, and behavioral responses.
      Prostaglandin (PG) E(2) is a metabolite from arachidonic acid, and exerts its
      functions through G-protein-coupled receptors called EP1, EP2, EP3, and EP4.
      Recent studies using knockout mice and selective drugs revealed the roles of
      these receptors in stress responses. Upon sickness, PGE(2) mediates fever through
      EP3, while both EP1 and EP3 are involved in ACTH release. In addition, EP1
      controls impulsive behaviors under psychological stress through the dopaminergic
      system. PGE(2) produced by various cell types may integrate multiple stress
      stimuli through PGE receptor subtypes for adaptive responses.

PMID- 19157988
TI  - SPORCalc: A development of a database analysis that provides putative metabolic
      enzyme reactions for ligand-based drug design.
AB  - Understanding both the enzyme reactions that contribute to intermediate
      metabolism and the biochemical fate of candidate therapeutic and toxic agents are
      essential for drug design. Traditional metabolic databases indicate whether
      reactions have been observed but do not provide the likelihoods of reactions
      occurring, for example those of mixed function oxygenases and oxidases, during
      phase I metabolism. The desire for more quantitative predictions motivated the
      development of the recently introduced Substrate Product Occurrence Ratio
      Calculator (SPORCalc) that identifies metabolically labile atom positions in
      candidate compounds. This paper describes a further development and provides a
      clearer explanation of SPORCalc for the computational pharmacology, medicinal
      chemistry and drug design communities interested in metabolic prediction of
      xenobiotics using chemical databases of biotransformations. Examples of reaction
      centre detection in Metabolite are described followed by a demonstration of
      almokalant, an anti-arrhythmic agent, undergoing phase I metabolism. In general,
      occurrence ratio (OR) values are calculated throughout a compound and its
      transformed metabolites to give propensity (p) values at each atom position. The
      OR values from substrates and products in the database are essential for addition
      and elimination reactions. For almokalant, the resulting p values ranged from 10(
      1) to 10(-5) and their order of magnitude reflected the known and experimentally
      observed metabolites. SPORCalc depends entirely on the level of detail from
      isoform- or species-specific reaction classes in Metabolite. Labile atom
      positions (sites of metabolism) are identified in both the candidate compound and
      its metabolites. In general, the likelihood of one enzyme isoform-dependent
      reaction occurring relative to another and the putative metabolic routes from
      different isoforms can be investigated. SPORCalc can be developed further to
      include suitable three-dimensional, structure-activity and physiochemical
      information.

PMID- 19157989
TI  - Mohan's valvotome for the ablation of posterior urethral valves.
AB  - INTRODUCTION: Treatment of posterior urethral valves (PUV) is now most commonly
      by endoscopic valve ablation, but this is not readily available in our
      environment. We describe our experience with Mohan's valvotome for the ablation
      of PUV. MATERIALS AND METHODS: All patients with PUV who underwent Mohan's
      valvotomy over a 28-month period from June 2006 were reviewed. RESULTS: There
      were 35 patients. The median age was 1.5 years (mean age 3.0 years, range 11 days
      to 14 years). Eleven (31.4%) and 24 (68.6%) patients received the treatment under
      local and general anaesthesia, respectively. Adequate relief of obstruction was
      achieved in all patients with marked improvement in the urinary stream.
      Complications were recorded in two (5.7%) patients; one was re-operated because
      of recurrent urinary retention, and the other had urinary incontinence which
      resolved after 3 months. At follow-up of 1-28 months (median 14 months), three
      (8.6%) patients had died from sepsis and malnutrition. The 32 (91.4%) surviving
      have good urinary stream, normal renal function (serum creatinine level
      <1.5mg/dl) and resolution of hydronephrosis as demonstrated on ultrasound. There
      was no mortality resulting directly from the use of Mohan's valvotomy.
      CONCLUSION: Mohan's valvotome is an effective instrument for the ablation of PUV.
      It is invaluable in the developing world where paediatric endoscopes are not
      readily available.

PMID- 19157990
TI  - The effects of ureteral obstruction on Cajal-like cells in rats.
AB  - OBJECTIVE: To determine the changes in number and morphology of interstitial
      cells of Cajal (ICC)-like cells (ICC-LC) at the ureteropelvic junction (UPJ) of
      rats after experimental distal ureteral obstruction. MATERIALS AND METHODS: Of a
      total of 109 rats, 20 served as controls (C), 20 underwent sham-operations (SH)
      and 69 were in the study (S) groups. The UPJs were extracted initially in the C
      and SH groups, and 7, 14, 30, 60 and 90 days after ligation of the distal ureter
      in the study groups (S1, S2, S3, S4 and S5, respectively). The sections stained
      by c-kit anticore were studied under a light microscope. RESULTS: The mean number
      of ICC-LC was 4.55+/-2.21 in C, 5.15+/-3.51 in SH, 7.40+/-6.88 in S1, 21.16+/
      19.03 in S2, 12.63+/-8.16 in S3, 10.40+/-5.09 in S4, and 10.9+/-6.33 in S5. There
      was a statistically significant increase in ICC-LC in the study groups, except
      S1, compared to the C and SH groups. No significant difference was detected in
      Cajal cell morphology and distribution pattern between groups. CONCLUSIONS: Based
      on the changes in number of ICC-LC at the UPJ after obstruction of the distal
      ureter compared with the limited data available in the literature, we suggest
      that ICC-LC have a close relationship with motility of the ureter.

PMID- 19157992
TI  - Intrathecal baclofen for autonomic instability due to spinal cord injury.
AB  - Autonomic dysreflexia may occur following spinal cord injury above mid-thoracic
      level, commonly developing in the early posttraumatic period. Cardiovascular
      dysregulation is the most prominent feature, characterized by paroxysmal high
      blood pressure attacks, which are precipitated by distension of urinary bladder
      or bowels, skin wounds, or increased spastic muscle tone. Severe drops in blood
      pressure may occur in orthostatic conditions. Baclofen is effective for treating
      spasticity. While orally administered baclofen often fails to alleviate severe
      spasticity adequately, intrathecal baclofen (ITB) is more effective and thus is
      being used increasingly. A 61-year-old male sustained a cervical spinal cord
      injury, subsequently developing severe spastic tetraparesis, predominantly in the
      legs. Some 30 years later he experienced marked spasms of the muscles of the
      abdominal wall, leading to extreme fluctuations of blood pressure. After positive
      evaluation with ITB the patient underwent implantation of a pump-catheter-system
      for continuous ITB application. Abdominal wall spasms ceased entirely with a
      daily dose of 190 microg ITB, accompanied by a sustained normotensive blood
      pressure profile. However, spasms reoccurred after inadvertent reduction of ITB
      flow when increasing the pump's ITB concentration but subsided again when the
      optimal antispastic dose was reestablished. Baclofen per se has the potential of
      lowering blood pressure. In this patient, however, ITB treatment enabled
      permanent stabilization of insidious blood pressure fluctuations. It would appear
      that suppression of abdominal spasms prevented the triggering of dysautonomic
      crises. This case demonstrates that ITB administration may help to stabilize
      autonomic dysreflexia and orthostatic hypotension in patients with spinal cord
      lesions.

PMID- 19157993
TI  - Fabrication of enzymatic glucose biosensor based on palladium nanoparticles
      dispersed onto poly(3,4-ethylenedioxythiophene) nanofibers.
AB  - A new methodology involving the combination of a soft template (surfactant) and
      an ionic liquid (co-surfactant) is used to electrodeposit poly(3,4
      ethylenedioxythiophene) (PEDOT) nanofibers. Electrochemical deposition of
      palladium nanoparticles and glucose oxidase (GOx) immobilization are done
      sequentially into nanofibrous PEDOT to fabricate the modified electrode (ME)
      (denoted as PEDOT-Pd/GOx-ME). The PEDOT-Pd/GOx-ME displays excellent performances
      for glucose at +0.4 V (vs. Ag/AgCl) with a high sensitivity (1.6 mA M(-)(1) cm(
      2)) in a wider linear concentration range, 0.5 to 30 mM (correlation coefficient
      of 0.9985). Further, the electrode is insusceptible to the electroactive
      interfering species.

PMID- 19157994
TI  - Interaction with DNA polymerase eta is required for nuclear accumulation of REV1
      and suppression of spontaneous mutations in human cells.
AB  - Defects in the gene encoding human Poleta result in xeroderma pigmentosum variant
      (XP-V), an inherited cancer-prone syndrome. Poleta catalyzes efficient and
      accurate translesion DNA synthesis (TLS) past UV-induced lesions. In addition to
      Poleta, human cells have multiple TLS polymerases such as Poliota, Polkappa,
      Polzeta and REV1. REV1 physically interacts with other TLS polymerases, but the
      physiological relevance of the interaction remains unclear. Here we developed an
      antibody that detects the endogenous REV1 protein and found that human cells
      contain about 60,000 of REV1 molecules per cell as well as Poleta. In un
      irradiated cells, formation of nuclear foci by ectopically expressed REV1 was
      enhanced by the co-expression of Poleta. Importantly, the endogenous REV1 protein
      accumulated at the UV-irradiated areas of nuclei in Poleta-expressing cells but
      not in Poleta-deficient XP-V cells. UV-irradiation induced nuclear foci of REV1
      and Poleta proteins in both S-phase and G1 cells, suggesting that these proteins
      may function both during and outside S phase. We reconstituted XP-V cells with
      wild-type Poleta or with Poleta mutants harboring substitutions in phenylalanine
      residues critical for interaction with REV1. The REV1-interaction-deficient
      Poleta mutant failed to promote REV1 accumulation at sites of UV-irradiation, yet
      (similar to wild-type Poleta) corrected the UV sensitivity of XP-V cells and
      suppressed UV-induced mutations. Interestingly however, spontaneous mutations of
      XP-V cells were only partially suppressed by the REV1-interaction deficient
      mutant of Poleta. Thus, Poleta-REV1 interactions prevent spontaneous mutations,
      probably by promoting accurate TLS past endogenous DNA lesions, while the
      interaction is dispensable for accurate Poleta-mediated TLS of UV-induced
      lesions.

PMID- 19157995
TI  - Differences in prevalence and treatment of Pseudomonas aeruginosa in cystic
      fibrosis centres in Denmark, Norway and Sweden.
AB  - BACKGROUND: Chronic Pseudomonas aeruginosa (PA) infection causes increased
      morbidity and mortality in cystic fibrosis (CF). This study aimed to answer the
      following questions: Does the prevalence of chronic infection with PA differ
      between the CF centres in Scandinavia? Which differences exist concerning
      segregation and treatment of PA? METHODS: 989 patients (86%) from all eight CF
      centres in Scandinavia were included. Demographic and clinical data, including PA
      colonisation status based on cultures and serology, were recorded at inclusion.
      The patients were followed prospectively for 1 year, recording number of days
      with anti-PA antibiotic treatment. RESULTS: In all pancreatic insufficient (PI)
      patients (n=890) the prevalence of chronic PA infection at each centre ranged
      from 25.8% to 48.9%, but were not significantly different. In PI patients <19
      years the prevalence was 14.5% in Copenhagen compared to 30.9% in the Swedish
      centres pooled (p=0.001). In intermittently colonised PI patients <19 years the
      median number of days per year on anti-PA antibiotics was almost 6 times higher
      in Copenhagen (mean 86 (110), median 61 days) compared to the Swedish centres
      pooled (mean 27 (52), median 11 days) (p=0.037). The pulmonary function was
      similar. CONCLUSIONS: It is possible to maintain a very low prevalence of chronic
      PA infection in CF patients <19 years. We speculate that this was most likely due
      to a very intensive treatment of intermittently colonised patients with inhaled
      anti-PA antibiotics over prolonged periods of time in some centres. Since lung
      function was similar in centres with less intensive use of inhaled antibiotics,
      studies comparing different treatment modalities and other parts of CF care are
      needed to define the best clinical practice, including how to use antibiotics in
      the most rational way.

PMID- 19157996
TI  - Method validation across the disciplines--critical investigation of major
      validation criteria and associated experimental protocols.
AB  - Analytical method development should aim at delivering reliable measurements
      within a given application. This implies that method validation is integrated in
      the development process, because it enables to establish a method's performance
      capabilities, and to demonstrate its fitness-for-purpose. Although analytical
      chemists mostly are familiar with the validation guidelines within the discipline
      of their responsibility, we believe that they may take advantage of a better
      acquaintance with recommendations among disciplines. Therefore, we review the
      guidance given in 4 disciplines (laboratory medicine, pharmacy, environment, and
      food), with emphasis on the proposed experimental protocols, acceptance criteria
      and interpretation strategies by statistical significance testing. Last but not
      least, we give incentive towards a modernized validation design.

PMID- 19157997
TI  - Quantitative analysis of RU38486 (mifepristone) by HPLC triple quadrupole mass
      spectrometry.
AB  - A sensitive liquid chromatography-mass spectrometric method was validated for the
      quantification of RU38486 (mifepristone) in human and murine plasma. The analyte
      and internal standard (alfaxolone) were extracted by liquid-liquid extraction
      with diethyl ether, resolved on a C18 column using gradient elution with methanol
      and ammonium acetate and detected after positive electrospray ionization (m/z 430
      ->372; m/z 333-->297, respectively). Quantification was linear over the range 0.5
      500ng (r(2)>0.997), precise and accurate (intra-assay RSD< or =7.2%, RME< or
      =8.2%; inter-assay RSD< or =15.7% RME< or =10.2%). The limit of quantification
      (LOQ) was 50pg injected on column, permitting reproducible analysis of RU38486 in
      small volumes of plasma.

PMID- 19157998
TI  - Quantitative analysis of short-chain acyl-coenzymeAs in plant tissues by LC-MS-MS
      electrospray ionization method.
AB  - Because acyl-CoAs play major roles in numerous anabolic and catabolic pathways,
      the quantitative determination of these metabolites in biological tissues is
      paramount to understanding the regulation of these metabolic processes. Here, we
      report a method for the analysis of a collection of short-chain acyl-CoAs (<6
      carbon chain length) from plant extracts. Identification of each individual acyl
      CoA was conducted by monitoring specific mass-fragmentation ions that are derived
      from common chemical moieties of all Coenzyme A (CoA) derivatives, namely the
      adenosine triphosphate nucleotide, pantothenate and acylated cysteamine. This
      method is robust and quick, enabling the quantitative analysis of up to 12
      different acyl-CoAs in plant metabolite extracts with minimal post-extraction
      processing, using a 30min chromatographic run-time.

PMID- 19157999
TI  - A high-performance liquid chromatography method for the quantification of
      cysmethynil, an inhibitor of isoprenylcysteine carboxylmethyl transferase, in
      mouse plasma.
AB  - Cysmethynil, a newly identified small molecule inhibitor of isoprenylcysteine
      carboxylmethyl transferase (Icmt) is involved in the post-translational
      modification of CaaX proteins. Cysmethynil causes cell death in many human cancer
      cells in vitro, and inhibits tumor growth in the xenograft mouse model in vivo. A
      HPLC method for the quantification of cysmethynil in mouse plasma was developed
      and validated. The lower limit of quantification of this method was
      0.01microg/ml. Inter- and intra-day variability ranged from 0.38-8.5% and
      accuracy was between 86% and 98%. This sensitive method was used to quantify
      cysmethynil in plasma of mice after intraperitoneal dosing for preliminary
      pharmacokinetic studies.

PMID- 19158000
TI  - A simple and sensitive HPLC-ESI-MS/MS method for the determination of
      andrographolide in human plasma.
AB  - A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC
      ESI-MS/MS) method for the determination of andrographolide in human plasma was
      established. Dehydroandrographolide was used as the internal standard (I.S.). The
      plasma samples were deproteinized with methanol and separated on a Hanbon C(18)
      column with a mobile phase of methanol-water (70:30, v/v). HPLC-ESI-MS/MS was
      performed in the selected ion monitoring (SIM) mode using target ions at [M-H(2)O
      H](-), m/z 331.1 for andrographolide and [M-H](-), m/z 331.1 for the I.S.
      Calibration curve was linear over the range of 1.0-150.0ng/mL. The
      chromatographic separation was achieved in less than 6.5min. The lower limits of
      quantification (LLOQ) was 1.0ng/mL. The intra and inter-run precisions were less
      than 6.95 and 7.22%, respectively. The method was successfully applied to
      determine the plasma concentrations of andrographolide in Chinese volunteers.

PMID- 19158001
TI  - Midodrine in the prevention of hepatorenal syndrome type 2 recurrence: a case
      control study.
AB  - BACKGROUND: Hepatorenal syndrome is a severe complication of cirrhosis. Treatment
      with terlipressin has currently the best efficacy pedigree, inducing hepatorenal
      syndrome reversal in a high proportion of patients. However, hepatorenal syndrome
      recurrence after terlipressin withdrawal is very common, especially in type 2
      hepatorenal syndrome. Midodrine, an oral adrenergic vasoconstrictor, has been
      suggested to be an effective therapy in hepatorenal syndrome. AIMS: To analyse
      the impact of treatment with midodrine after hepatorenal syndrome type 2 reversal
      induced by terlipressin on the prevention of hepatorenal syndrome recurrence.
      PATIENTS AND METHODS: A case-control design was used. The outcome of 10 patients
      with hepatorenal syndrome type 2 treated successfully with terlipressin and then
      with midodrine (7.5-12.5mg/tid) was compared with that of an historical control
      group of hepatorenal syndrome type 2 patients responders to treatment with
      terlipressin. Patients and controls were matched by age, plasma renin activity
      (PRA) levels and severity of renal and liver failure. RESULTS: Cases and controls
      were similar with respect to pre-treatment with terlipressin. The hepatorenal
      syndrome recurrence probability was the same in the two groups (cases and
      control: 9/10, 90%, p=ns). No significant differences were found between cases
      and controls with respect to serum creatinine (1.9+/-0.1mg/dl vs. 2+/-0.2mg/dl),
      blood creatinine clearance (28+/-5ml/min vs. 24+/-5ml/min), urinary sodium
      excretion (12+/-6mequiv./d vs. 19+/-4mequiv./d) and PRA levels (17+/-3ng/ml/h)
      vs. 20+/-3ng/ml/h) after terlipressin withdrawal (p=ns). CONCLUSIONS: These
      results show that in patients responders to terlipressin hepatorenal syndrome
      recurrence is not different between patients treated with midodrine and subjects
      who did not receive vasoconstrictor treatment after terlipressin withdrawal.
      These data suggest that midodrine is not effective in preventing hepatorenal
      syndrome type 2 recurrence.

PMID- 19158002
TI  - Optimal preparation for small bowel examinations with video capsule endoscopy.
AB  - BACKGROUND: Video capsule endoscopy is a major advance for small bowel
      exploration. Although the clinical benefit is well accepted, there are still
      unresolved issues concerning patient preparation. AIM: This study was set up in
      order to clarify the clinical benefit of small bowel preparation and give advices
      in order to obtain the best results for this expensive device. METHOD: 116
      patients were randomised in 3 centres between two preparations from the
      traditional liquid diet versus polyethylene glycol colonoscopy-like preparation.
      External viewer monitoring and recording pictures were focused on image quality,
      bubbles or diet residues. Picture qualities were assessed blindly. RESULTS: For
      jejunal exploration no differences were noticed between the two preparations but
      for the ileum, polyethylene glycol preparation gives significant better results
      than liquid diet: air bubbles (64.4% versus 29.8% p<0.05); opaque residue (83.1%
      versus 38.6% p<0.05). External viewer was useful in order to use prokinetic drugs
      in case of delayed gastric emptying. CONCLUSION: The result leads to a new advice
      for colleagues in handling patients in order to improve the diagnosis yield by
      using a modified polyethylene glycol preparation.

PMID- 19158003
TI  - Microbial biofilm growth vs. tissue integration: "the race for the surface"
      experimentally studied.
AB  - Biomaterial-associated infections constitute a major clinical problem.
      Unfortunately, microorganisms are frequently introduced onto an implant surface
      during surgery and start the race for the surface before tissue integration can
      occur. So far, no method has been forwarded to study biofilm formation and tissue
      integration simultaneously. The aim of this study is to describe an in vitro
      method to investigate this "race for the surface". First, a suitable growth
      medium was prepared that allowed both bacterial and tissue growth in a parallel
      plate flow chamber. Staphylococci were deposited on the glass bottom plate of the
      flow chamber in different surface densities, after which U2OS osteosarcoma cells
      were seeded. U2OS cells did not grow in the absence of flow, possibly due to
      poisoning by bacterial endotoxins, but under flow both staphylococci and U2OS
      cells grew. The number of adhering cells and area per spread cell were determined
      after 48 h in relation to the initial number of bacteria present. Both the number
      and spread area per cell decreased with increasing density of adhering
      staphylococci. This demonstrates that the outcome of the race for the surface
      between bacteria and tissue cells is dependent on the number of bacteria present
      prior to cell seeding.

PMID- 19158004
TI  - New technologies in ambulatory thyroid surgery.
AB  - Thyroid operations are increasingly performed in the outpatient setting. In
      general the essential objectives for thyroidectomy are: sparing the parathyroid
      glands, avoidance of injury to the laryngeal nerves, an accurate hemostasis and
      an excellent cosmesis. In the last 10 years major improvements and new
      technologies have been proposed and applied in thyroid surgery; among these mini
      invasive thyroidectomy, new devices for achieving hemostasis and dissection,
      intraoperative neuromonitoring, and PTH assay technology. This paper reviews
      relevant medical literature published on the influence of these new technologies
      on quality of thyroid surgery as well as prevention of postoperative morbidity
      and mortality. Searches were last updated April 2008.

PMID- 19158005
TI  - Evaluation of facial growth in non-cleft patients using the analysis method for
      patients after a cleft lip and/or palate repair.
AB  - Analysis of the soft tissue profile is recognized as an important aspect for
      assessing the effect of different surgical methods in patients with a cleft lip
      and/or palate. Two hundred seventy healthy people with deciduous, mixed and
      permanent dentition were chosen for photographs. The photographs were measured
      and the ratios were calculated using the aesthetic indexes of the nasal and lip
      region used for evaluating cleft lip and palate repairs. Results revealed six
      measurements were symmetrical in non-cleft patients and the range of ratios was
      from 99.8% to 106.88%. This study indicated that the indexes were important for
      evaluation of cleft lip and palate repair. Based on the above results it was
      concluded that surgery was successful if the ratio was less than 10% when
      compared to non-cleft patients.

PMID- 19158006
TI  - Gracilis muscle interposition for the treatment of recto-urethral and
      rectovaginal fistulas: a retrospective analysis of 35 cases.
AB  - BACKGROUND: Several surgical procedures for the repair of fistulas between the
      rectum and the urethra or vagina have been reported. Our study was designed to
      assess the efficacy of the gracilis muscle flap in repairing recto-urethral and
      rectovaginal fistulas. METHODS: Gracilis muscle interposition flaps were
      performed in 35 patients (aged 38-78 years, mean: 58 years) using a perineal
      approach. Nine patients had rectovaginal fistulas due to Crohn's disease (n=3),
      previous surgery and pelvic irradiation for rectal (n=2) or cervical cancer
      (n=4). Twenty-six fistulas were recto-urethral. The aetiologies were Crohn's
      disease (n=4), brachytherapy after prostate cancer (n=14), iatrogenic injury to
      the rectum during radical retropubic prostatectomy (n=4), transurethral resection
      of the prostate (n=2) and recurrent peri-anal abscesses with fistulas (n=2).
      Twenty-five patients had undergone previous repair attempts; of these four
      underwent multiple procedures. Patient outcomes were assessed after surgical
      repair. The success rate was measured as the percentage of patients with a healed
      fistula after stomal closure. RESULTS: The mean follow-up was 28+/-15 months from
      muscle transposition and 22+/-14 months from stomal closure. Fistula closure with
      no recurrence could be achieved in 33 patients (94%). Two of the seven patients
      (29%) with Crohn's disease had a persistent fistula. There were neither intra
      operative complications nor problems related to muscle desinsertion surgery.
      CONCLUSIONS: Recto-urethral and rectovaginal fistula closure using the perineal
      approach with pedicled gracilis muscle interposition is associated with minimal
      morbidity and a high success rate. It is an excellent option for patients with
      complicated fistulas for whom other surgical treatments have failed. Underlying
      Crohn's disease is associated with a higher complication rate.

PMID- 19158007
TI  - Midterm outcome of the modified Bretteville technique for hypospadias
      reconstruction.
AB  - Hypospadias is a common condition affecting approximately one in 300 boys in
      Scotland. The functional and aesthetic outcome of the many different techniques
      of repair are being analysed in increasingly critical fashion. However, few
      techniques have been published with more than short-term follow-up data. The
      modified Bretteville technique is a two-stage technique that can be used for all
      degrees of severity of hypospadias. It has certain advantages over other single-
      and two-stage techniques. We present the midterm results of 74 hypospadias
      corrections performed by using the modified Bretteville technique. The majority
      of hypospadias were distal (93%), but the series includes patients with mid-shaft
      and proximal deformity. The mean follow-up period was 67 months (range: 5-126).
      The average number of procedures per patient was 2.35, and 78% of patients had
      only two procedures. The overall fistula rate was 5.4% and the stenosis rate was
      6.8%, though this figure has fallen to 2.6% for the fistula rate (n=38) and 0%
      for the stenosis rate (n=38) over the most recent 5-year follow-up period. One
      patient needed re-repair using a Bracka technique. We believe that the modified
      Bretteville technique is a reliable technique for proximal, as well as distal,
      hypospadias with an excellent cosmetic outcome.

PMID- 19158008
TI  - The approach to cardiac CT imaging in obese patients is not "one size fits all".

PMID- 19158009
TI  - Physical methods for investigating structural colours in biological systems.
AB  - Many biological systems are known to use structural colour effects to generate
      aspects of their appearance and visibility. The study of these phenomena has
      informed an eclectic group of fields ranging, for example, from evolutionary
      processes in behavioural biology to micro-optical devices in technologically
      engineered systems. However, biological photonic systems are invariably
      structurally and often compositionally more elaborate than most synthetically
      fabricated photonic systems. For this reason, an appropriate gamut of physical
      methods and investigative techniques must be applied correctly so that the
      systems' photonic behaviour may be appropriately understood. Here, we survey a
      broad range of the most commonly implemented, successfully used and recently
      innovated physical methods. We discuss the costs and benefits of various
      spectrometric methods and instruments, namely scatterometers,
      microspectrophotometers, fibre-optic-connected photodiode array spectrometers and
      integrating spheres. We then discuss the role of the materials' refractive index
      and several of the more commonly used theoretical approaches. Finally, we
      describe the recent developments in the research field of photonic crystals and
      the implications for the further study of structural coloration in animals.

PMID- 19158010
TI  - Incorporating demographic stochasticity into multi-strain epidemic models:
      application to influenza A.
AB  - We develop mathematical models of the transmission and evolution of multi-strain
      pathogens that incorporate strain extinction and the stochastic generation of new
      strains via mutation. The dynamics resulting from these models is then examined
      with the applied aim of understanding the mechanisms underpinning the evolution
      and dynamics of rapidly mutating pathogens, such as human influenza viruses. Our
      approach, while analytically relatively simple, gives results that are
      qualitatively similar to those obtained from much more complex individually based
      simulation models. We examine strain dynamics as a function of cross-immunity and
      key transmission parameters, and show that introducing strain extinction and
      modelling mutation as a stochastic process significantly changes the model
      dynamics, leading to lower strain diversity, reduced infection prevalence and
      shorter strain lifetimes. Finally, we incorporate transient strain-transcending
      immunity in the model and demonstrate that it reduces strain diversity further,
      giving patterns of sequential strain replacement similar to that seen in human
      influenza A viruses.

PMID- 19158011
TI  - Passive versus active engulfment: verdict from trajectory simulations of lunge
      feeding fin whales Balaenoptera physalus.
AB  - Lunge-feeding in rorqual whales represents the largest biomechanical event on
      Earth and one of the most extreme feeding methods among aquatic vertebrates. By
      accelerating to high speeds and by opening their mouth to large gape angles,
      these whales generate the water pressure required to expand their mouth around a
      large volume of prey-laden water. Such large influx is facilitated by highly
      extensible ventral groove blubber (VGB) associated with the walls of the throat
      (buccal cavity). Based on the mechanical properties of this tissue, previous
      studies have assumed lunge-feeding to be an entirely passive process, where the
      flow-induced pressure driving the expansion of the VGB is met with little
      resistance. Such compliant engulfment would be facilitated by the compliant
      properties of the VGB that have been measured on dead specimens. However,
      adjoining the ventral blubber are several layers of well-developed muscle
      embedded with mechanoreceptors, thereby suggesting a capability to gauge the
      magnitude of engulfed water and use eccentric muscle action to control the flux
      of water into the mouth. An unsteady hydrodynamic model of fin whale lunge
      feeding is presented here to test whether engulfment is exclusively passive and
      compliant or involves muscle action. The model is based on the explicit
      simulation of the engulfed water as it interacts with the buccal cavity walls of
      the whale, under different heuristically motivated cavity forces. Our results,
      together with their comparison with velocity data collected in the field, suggest
      that adult rorquals actively push engulfed water forward from the very onset of
      mouth opening in order to successfully complete a lunge. Interestingly, such an
      action involves a reflux of the engulfed mass rather than the oft-assumed
      rebound, which would occur mainly at the very end of a lunge sequence dominated
      by compliant engulfment. Given the great mass of the engulfed water, reflux
      creation adds a significant source of hydrodynamic drag to the lunge process, but
      with the benefit of helping to circumvent the problem of removing prey from
      baleen by enhancing the efficiency of cross-flow filtration after mouth closing.
      Reflux management for a successful lunge will therefore demand well-coordinated
      muscular actions of the tail, mouth and ventral cavity.

PMID- 19158012
TI  - Model validation of simple-graph representations of metabolism.
AB  - The large-scale properties of chemical reaction systems, such as metabolism, can
      be studied with graph-based methods. To do this, one needs to reduce the
      information, lists of chemical reactions, available in databases. Even for the
      simplest type of graph representation, this reduction can be done in several
      ways. We investigate different simple network representations by testing how well
      they encode information about one biologically important network structure
      network modularity (the propensity for edges to be clustered into dense groups
      that are sparsely connected between each other). To achieve this goal, we design
      a model of reaction systems where network modularity can be controlled and
      measure how well the reduction to simple graphs captures the modular structure of
      the model reaction system. We find that the network types that best capture the
      modular structure of the reaction system are substrate-product networks (where
      substrates are linked to products of a reaction) and substance networks (with
      edges between all substances participating in a reaction). Furthermore, we argue
      that the proposed model for reaction systems with tunable clustering is a general
      framework for studies of how reaction systems are affected by modularity. To this
      end, we investigate statistical properties of the model and find, among other
      things, that it recreates correlations between degree and mass of the molecules.

PMID- 19158013
TI  - Chemometric analysis for comparison of heparan sulphate oligosaccharides.
AB  - Heparan sulphate (HS) is a glycosaminoglycan present in all metazoan organisms.
      It is an unbranched chain made up of repeating disaccharide units of uronic acid
      and glucosamine sugars, and is present in both cells and the extracellular
      matrix. It is one of the most structurally diverse biological molecules and its
      biosynthesis involves a variety of enzymic modification steps. Unlike the genome
      and the transcriptome, HS synthesis is not template driven. Nevertheless, the HS
      structure and function are highly regulated with modification steps occurring in
      discrete regions of the polysaccharide chain to give rise to diverse structures
      interacting with, and regulating, many different proteins. The resulting
      variation leads to diverse biological roles of HS. To study this structural
      diversity, rapid isolation and characterization of HS from small amounts of
      tissues, followed by digestion with bacterially derived enzymes (heparitinases)
      and chromatography techniques can be used to separate HS oligosaccharides of
      different size and charge. However, this leads to complex datasets where
      comparison of just a few samples leads to difficulties in data analysis. Using
      automatically integrated peak data obtained from chromatographic software, one
      can apply the effective disc technique to the data points to obtain the centre of
      mass in each dataset, for example from different murine tissues. This allows
      facile comparative analysis of different datasets. When the cloud of points
      displays some preferential direction (anisotropy), it is preferable to compute
      its effective ellipse. Analysis of the dynamics of the cloud of points for
      repeated experiments allows the quantification of their reproducibility through
      evaluation of an average Lyapunov exponent characterizing the area-preserving
      nature of a sequence of effective ellipses. These basic mathematical approaches
      allow a more systematic comparison of datasets derived from structural analysis
      using basic spreadsheet software calculations and contribute to the development
      of system biology strategies for tackling biocomplexity of HS polysaccharides.

PMID- 19158014
TI  - An overview of biofunctionalization of metals in Japan.
AB  - Surface modification is an important and predominant technique for obtaining
      biofunction and biocompatibility in metals for biomedical use. The surface
      modification technique is a process that changes the surface composition,
      structure and morphology of a material, leaving the bulk mechanical properties
      intact. A tremendous number of surface modification techniques using dry and wet
      processes to improve the hard tissue compatibility of titanium have been
      developed. Some are now commercially available. Most of these processes have been
      developed by Japanese institutions since the 1990 s. A second approach is the
      immobilization of biofunctional molecules to the metal surface to control the
      adsorption of proteins and adhesion of cells, platelets and bacteria. The
      immobilization of poly(ethylene glycol) to a metal surface with electrodeposition
      and its effect on biofunction are reviewed. The creation of a metal-polymer
      composite is another way to obtain metal-based biofunctional materials. The
      relationship between the shear bonding strength and the chemical structure at the
      bonding interface of a Ti-segmentated polyurethane composite through a silane
      coupling agent is explained.

PMID- 19158015
TI  - Bioactive ceramic-based materials with designed reactivity for bone tissue
      regeneration.
AB  - Bioactive ceramics have been used clinically to repair bone defects owing to
      their biological affinity to living bone; i.e. the capability of direct bonding
      to living bone, their so-called bioactivity. However, currently available
      bioactive ceramics do not satisfy every clinical application. Therefore, the
      development of novel design of bioactive materials is necessary. Bioactive
      ceramics show osteoconduction by formation of biologically active bone-like
      apatite through chemical reaction of the ceramic surface with surrounding body
      fluid. Hence, the control of their chemical reactivity in body fluid is essential
      to developing novel bioactive materials as well as biodegradable materials. This
      paper reviews novel bioactive materials designed based on chemical reactivity in
      body fluid.

PMID- 19158017
TI  - [Antithrombotic therapy in primary and secondary stroke prevention of cardiac
      patients and in acute stroke].
AB  - Primary vascular prevention: the prevalence of cardiogenic stroke will increase
      in the future. All patients with atrial fibrillation but without any ischemic
      stroke, must undergo a rigorous risk evaluation, which is crucial for
      pharmacotherapy. Atrial fibrillation is an important risk factor for stroke,
      therefore patients with atrial fibrillation should be anticoagulated (except
      those without other risk factors). Even patients over 75 years with atrial
      fibrillation could be anticoagulated if the INR is properly controlled. The
      authors review also the role of anticoagulation in patients suffering from
      myocardial infarction or valve diseases. Acute stroke: The new European stroke
      guideline does not recommend the use of conventional or fractionated heparin in
      the first three days of acute stroke, but aspirin therapy is recommended. Long
      term anticoagulation is needed only if cardiac source of emboli can be verified,
      the patient has good compliance, and the risk of hemorrhagic complication is low
      (INR: 2-3). Otherwise, antiplatelet therapy is recommended. Some authors
      recommend early anticoagulation in special cases (high risk of embolisation, left
      atrial/ventricular thrombus, arterial dissection or surgical intervention for a
      severe arterial stenosis). Caution is needed in patients with large infarct,
      uncontrolled hypertension and microbleeds on MRI. Secondary prevention:
      Antiplatelet therapy is recommended for every post-stroke patient, but for those
      with cardiac source of emboli anticoagulation is recommended.

PMID- 19158016
TI  - Electron tomography, three-dimensional Fourier analysis and colour prediction of
      a three-dimensional amorphous biophotonic nanostructure.
AB  - Organismal colour can be created by selective absorption of light by pigments or
      light scattering by photonic nanostructures. Photonic nanostructures may vary in
      refractive index over one, two or three dimensions and may be periodic over large
      spatial scales or amorphous with short-range order. Theoretical optical analysis
      of three-dimensional amorphous nanostructures has been challenging because these
      structures are difficult to describe accurately from conventional two-dimensional
      electron microscopy alone. Intermediate voltage electron microscopy (IVEM) with
      tomographic reconstruction adds three-dimensional data by using a high-power
      electron beam to penetrate and image sections of material sufficiently thick to
      contain a significant portion of the structure. Here, we use IVEM tomography to
      characterize a non-iridescent, three-dimensional biophotonic nanostructure: the
      spongy medullary layer from eastern bluebird Sialia sialis feather barbs.
      Tomography and three-dimensional Fourier analysis reveal that it is an amorphous,
      interconnected bicontinuous matrix that is appropriately ordered at local spatial
      scales in all three dimensions to coherently scatter light. The predicted
      reflectance spectra from the three-dimensional Fourier analysis are more precise
      than those predicted by previous two-dimensional Fourier analysis of transmission
      electron microscopy sections. These results highlight the usefulness, and
      obstacles, of tomography in the description and analysis of three-dimensional
      photonic structures.

PMID- 19158018
TI  - [Chemo- and radiotherapy of germ cell testicular cancer in the literature].
AB  - The study reviews the incidence, histologic types and prognostic factors of
      testicular cancer. The measurement of tumor-marker levels before castration
      determine the further activity regarding the data of imagings. The authors
      explain the treatment of seminoma and non-seminoma by stages. Carboplatin
      monotherapy is equivalent to the irradiation in early seminoma cases. Nowadays
      applied second and third line chemotherapies are reviewed. It is necessary to
      take into consideration not only the remission rate but also the late toxicity
      during the complex treatment of testicular germ cell cancer.

PMID- 19158019
TI  - [Postoperative wound healing disorders].
AB  - AIM: Investigation of the incidence of wound healing disorders in operative
      material and that of possible commonality with the nosocomial categories of
      operations and with the surgical site infections registered by the authors,
      respectively. OPERATIVE MATERIAL AND METHOD: The data of 33,336 operations, made
      in their ward, are analysed by the authors. By way of introduction the question
      of nomenclature is discussed which is not uniform in the literature. Referring to
      the most accepted infection surveillance systems they state that wound healing
      disorders represent a different idea than surgical site infections. The method of
      their prospective investigation is described as follows: at the time of the
      emission of the patient every wound healing disorder is registered in a
      collective protocol and in a short case history. Then they are monthly
      summarised. The data were elaborated in one year, in 5 years, in 10 years and in
      20 years grouping interconnected with the nosocomial categories of the
      operations, and with the surgical site infections observed in the same period of
      time. RESULTS: The numerical results are debated in detail. These show that the
      20-year summarised rate of wound healing disorders amounts to 2.2% and that of
      surgical site infections to 2.7%. They point out that the rates of both wound
      healing disorders and surgical site infections are diminishing during the second
      half of observation. The former is related to the improved surgical technique and
      to the better operative circumstances introduced during the observed two decades.
      The latter can be a consequence of their prospective infection register based on
      the CDC ad HELICS systems. CONCLUSIONS: Up till now no information could be found
      by them in the literature concerning the interaction of wound healing disorders
      with the nosocomial categories of the performed operations. The author's new
      establishment: as proceeding from category "A" towards category "D", not only the
      rates of surgical site infections became greater and greater, but those of wound
      healing disorders, too. But there is an important difference: the increase of the
      rates of wound healing disorders is in general meaningfully less than that of
      surgical site infections. Concerning the interaction of wound healing disorders
      with surgical site infections also another original observation was made by them:
      if the rate of surgical site infections is less than 2%, the identical rate of
      wound healing disorders is greater than the rate of surgical site infections and
      vice versa. If the rate of surgical site infections is greater than 2%, the rate
      of wound healing disorders becomes less than the rate of site infections. In
      conclusion the authors think that this relationship between the two sorts of
      rates - which can be seen in the majority (82.5%) of the rates of wound healing
      disorders and identical surgical site infections - seems to be fundamental. The
      interpretation of this observation can be done as follows: all wound healing
      disorders represent "loci minoris resistentiae" concerning the infection. They
      don't suppurate, or they scarcely suppurate in the aseptic category "A" and in
      the facultative septic category "B". On the other hand, more and more of their
      proportion becomes suppurated in the septic category "C", and even more in the
      seriously septic category "D". Finally they refer to their guessing, whereby, in
      an adequate context, the rates of wound healing disorders could be perhaps new
      indicators in surgical quality assurance.

PMID- 19158020
TI  - [The effect of low-protein diet supplemented with ketoacids in patients with
      chronic renal failure].
AB  - It is known that dietary protein restriction slows the progression of chronic
      renal disease. If daily protein intake is less than 0.5-0.6 g/kgbw, the diet has
      to be supplemented with essential aminoacids/ketoacids. In this study the authors
      evaluate the long-term effect of low-protein diet supplemented with ketoacids on
      the progression of chronic renal failure, calcium and phosphorus metabolism,
      nutritional status, the compliance of patients and the permanent dietary
      education for the compliance. 51 predialysis patients have been treated with
      ketoacids supplemented low-protein diet during 12-57 months (mean treatment
      period: 26 months). Serum creatinine raised from 349.72+/-78.04 micromol/l to
      460.66+/-206.66 micromol/l (27 micromol/l/year or 2.3 micromol/l/month),
      glomerular filtration rate (GFR) decreased from 21.52+/-7.84 ml/min to 18.22+/
      7.76 ml/min (0.83 ml/min/year or 0.07 ml/min/month). The slope of 1/serum
      creatinine versus time was 0.0018 by linear regression analysis. Serum
      parathormon decreased significantly, but serum calcium and phosphorus did not
      change. Nutritional status of patients did not change significantly during the
      follow-up period. Protein intake decreased significantly and remained at this
      lower level during the treatment period. According to results: low-protein diet
      supplemented with ketoacids was effective in slowing progression of chronic renal
      failure, decreased PTH, did not change nutritional status. With permanently and
      good education it was possible to keep patients on low-protein diet for a long
      period.

PMID- 19158021
TI  - [Home parenteral nutrition. May it be performed in Hungary, too?].
AB  - Patients suffering from intestinal failure can receive home parenteral nutrition
      in several countries of the world since the end of the 1960s. In Hungary,
      intestinal failure patients can receive parenteral nutrition only in hospital,
      even if they can live in family or they are capable to work under certain
      circumstances because the present health financial system and legal environment
      do not allow home parenteral nutrition. This system is extremely uneconomical,
      reserves hospital beds and is opposing the European practice. Based on literature
      of recent years, the authors reviewed the life expectancy, the quality of life of
      patients receiving home parenteral nutrition and the frequency of complications
      and home parenteral nutrition systems applied worldwide. The specialized
      knowledge needed for home parenteral nutrition is entirely available, the
      solutions and technical supports are ready in the Hungarian market. Professionals
      committed to nutrition therapy have initiated academic collaboration among
      specialties to arrange the poorly handled questions of home parenteral nutrition
      and to establish the home parenteral nutrition system in Hungary.

PMID- 19158025
TI  - Interactions between background matching and motion during visual detection can
      explain why cryptic animals keep still.
AB  - A widespread example of coevolution between behaviour and morphology is that
      crypsis is associated with motionlessness. Surprisingly, however, the adaptive
      function of this association has never been investigated experimentally. We
      tested whether the risk of being detected by a predator is affected by crypsis,
      movement or an interaction between these two traits. We show that, to avoid being
      detected and attacked by three-spined sticklebacks (Gasterosteus aculeatus L.),
      chironomid larvae need both to match their background and to keep still.
      Additionally, relatively more active individuals were targeted from cryptic prey
      groups, but not from conspicuous ones. Therefore, rather than crypsis and keeping
      still both contributing to reducing detection, the two traits are synergistic in
      reducing detection rates. This interdependence has implications for the
      coevolution of background matching and motion, and also between anti-predator
      traits and predators' visual systems.

PMID- 19158027
TI  - Deep-sea mystery solved: astonishing larval transformations and extreme sexual
      dimorphism unite three fish families.
AB  - The oceanic bathypelagic realm (1000-4000 m) is a nutrient-poor habitat. Most
      fishes living there have pelagic larvae using the rich waters of the upper 200 m.
      Morphological and behavioural specializations necessary to occupy such
      contrasting environments have resulted in remarkable developmental changes and
      life-history strategies. We resolve a long-standing biological and taxonomic
      conundrum by documenting the most extreme example of ontogenetic metamorphoses
      and sexual dimorphism in vertebrates. Based on morphology and mitogenomic
      sequence data, we show that fishes currently assigned to three families with
      greatly differing morphologies, Mirapinnidae (tapetails), Megalomycteridae
      (bignose fishes) and Cetomimidae (whalefishes), are larvae, males and females,
      respectively, of a single family Cetomimidae. Morphological transformations
      involve dramatic changes in the skeleton, most spectacularly in the head, and are
      correlated with distinctly different feeding mechanisms. Larvae have small,
      upturned mouths and gorge on copepods. Females have huge gapes with long,
      horizontal jaws and specialized gill arches allowing them to capture larger prey.
      Males cease feeding, lose their stomach and oesophagus, and apparently convert
      the energy from the bolus of copepods found in all transforming males to a
      massive liver that supports them throughout adult life.

PMID- 19158028
TI  - Assessment and decision-making in a Caribbean damselfish: nest-site quality
      influences prioritization of courtship and brood defence.
AB  - In systems where territory quality varies, animals are expected to exhibit
      plasticity in behaviour in order to maximize fitness relative to their present
      territory quality. This requires assessment of territory quality followed by
      decision-making in relation to the priority of activities necessary for survival
      and reproduction. We examined how differences in territory quality of beaugregory
      damselfish (Stegastes leucostictus) influence the prioritization of courtship and
      egg defence by comparing behavioural responses of males defending artificial
      sites (high quality) with males defending natural sites (low quality) when
      presented with an egg predator, a conspecific female, and a simultaneous choice
      between both. A significant three-way interaction of territory quality,
      presentation type and stimulus was observed for time near stimuli. In paired
      presentations, males defending low-quality territories spent more time near a
      female and less near an egg predator; while males on high-quality territories
      spent more time near a predator than a female. Additionally, comparing single and
      paired presentations reveals that behaviours towards egg predators remain
      constant while behaviours towards females decrease with paired stimuli. These
      data suggest that territory quality and ecological context impact decision-making
      and the relative values of potential reproduction and/or past reproductive
      effort.

PMID- 19158029
TI  - Free amino acids as phagostimulants in cricket nuptial gifts: support for the
      'Candymaker' hypothesis.
AB  - Nuptial gifts that are manufactured by the male are found in numerous insect
      species and some spiders, but there have been very few studies of the composition
      of such gifts. If, as has been proposed recently, nuptial gifts represent sensory
      traps, males will be selected to produce gifts that are attractive to females but
      such gifts will not necessarily provide the female with nutritional benefits (the
      'Candymaker' hypothesis). We examined the free amino acid content of the
      spermatophylax of the cricket Gryllodes sigillatus (Orthoptera: Gryllidae) using
      high performance liquid chromatography (HPLC). The spermatophylax (dry weight)
      consisted of approximately 7 per cent free amino acids. The free amino acid
      composition was highly imbalanced, with a low proportion of essential amino acids
      (18.7%) and a high proportion of proline and glycine. The main free amino acids
      found in the spermatophylax appeared to act as phagostimulants: the duration of
      feeding on artificial gels by females was positively related to the free amino
      acid content of the gels. The results therefore suggest that males use free amino
      acids to 'sweeten' a relatively low-value food item. A possible function of
      glycine in inhibiting female movement is also proposed.

PMID- 19158030
TI  - From coprophagy to predation: a dung beetle that kills millipedes.
AB  - The dung beetle subfamily Scarabaeinae is a cosmopolitan group of insects that
      feed primarily on dung. We describe the first case of an obligate predatory dung
      beetle and contrast its behaviour and morphology with those of its coprophagous
      sympatric congeners. Deltochilum valgum Burmeister killed and consumed millipedes
      in lowland rainforest in Peru. Ancestral ball-rolling behaviour shared by other
      canthonine species is abandoned, and the head, hind tibiae and pygidium of D.
      valgum are modified for novel functions during millipede predation. Millipedes
      were killed by disarticulation, often through decapitation, using the clypeus as
      a lever. Beetles killed millipedes much larger than themselves. In pitfall traps,
      D. valgum was attracted exclusively to millipedes, and preferred injured over
      uninjured millipedes. Morphological similarities placing D. valgum in the same
      subgenus with non-predatory dung-feeding species suggest a major and potentially
      rapid behavioural shift from coprophagy to predation. Ecological transitions
      enabling the exploitation of dramatically atypical niches, which may be more
      likely to occur when competition is intense, may help explain the evolution of
      novel ecological guilds and the diversification of exceptionally species-rich
      groups such as insects.

PMID- 19158031
TI  - Tropical deforestation alters hummingbird movement patterns.
AB  - Reduced pollination success, as a function of habitat loss and fragmentation,
      appears to be a global phenomenon. Disruption of pollinator movement is one
      hypothesis put forward to explain this pattern in pollen limitation. However, the
      small size of pollinators makes them very difficult to track; thus, knowledge of
      their movements is largely speculative. Using tiny radio transmitters (0.25 g),
      we translocated a generalist tropical 'trap-lining' hummingbird, the green hermit
      (Phaethornis guy), across agricultural and forested landscapes to test the
      hypothesis that movement is influenced by patterns of deforestation. Although, we
      found no difference in homing times between landscape types, return paths were on
      average 459+/-144 m (+/-s.e.) more direct in forested than agricultural
      landscapes. In addition, movement paths in agricultural landscapes contained 36+/
      4 per cent more forest than the most direct route. Our findings suggest that this
      species can circumvent agricultural matrix to move among forest patches.
      Nevertheless, it is clear that movement of even a highly mobile species is
      strongly influenced by landscape disturbance. Maintaining landscape connectivity
      with forest corridors may be important for enhancing movement, and thus in
      facilitating pollen transfer.

PMID- 19158032
TI  - Selective harvesting with equations: comment on 'should hunting mortality mimic
      the patterns of natural mortality?'.

PMID- 19158034
TI  - The rapid evolution of breast cancer therapeutic agents.

PMID- 19158035
TI  - Incorporation of antiangiogenic therapies in the treatment of metastatic breast
      cancer.
AB  - Angiogenesis plays a central role in the development of metastasis in breast
      cancer. Recent results of large randomized trials show clinically significant
      improvements in outcomes with the use of bevacizumab in patients with metastatic
      breast cancer, leading to approval by European and US regulatory agencies.
      Several other antiangiogenic strategies are in various stages of development.
      This review discusses the results of recent clinical trials and novel mechanisms
      of inhibiting angiogenesis, resistance mechanisms, and toxicities; and raises key
      challenges that face optimal use and development of antiangiogenic agents in
      breast cancer.

PMID- 19158036
TI  - Current paradigms for the use of HER2-targeted therapy in early-stage breast
      cancer.
AB  - Results are now available from 6 trials randomizing > 14,000 women with HER2
      positive early breast cancer to trastuzumab versus non-trastuzumab-based adjuvant
      chemotherapy. Aside from the recently presented PACS 04 trial, these studies
      demonstrate remarkably consistent results: the addition of trastuzumab reduces
      recurrence by approximately 50% and improves overall survival by 30%,
      irrespective of tumor size, nodal status, schedule of administration, and type of
      chemotherapy administered. There remain many unanswered questions regarding
      optimal adjuvant trastuzumab use, including the relationship between trastuzumab
      efficacy and markers of HER2 assessment (HER2 protein expression, gene copy
      number, and chromosome 17 polysomy); the selection of patients for non
      anthracycline-based chemotherapy; the decision to administer trastuzumab in a
      sequential or concurrent manner with chemotherapy; and the minimal effective
      duration of trastuzumab required for adjuvant therapy. Future studies with novel
      anti-HER2 strategies will prospectively evaluate biomarkers in an effort to
      further improve the outcome of women diagnosed with HER2-positive disease.

PMID- 19158037
TI  - Integrating epothilones into the treatment of patients with metastatic breast
      cancer: clinical perspectives on incorporating recent data in the practice
      setting.
AB  - The introduction of modern chemotherapy agents, including the taxanes, has
      improved the prognosis of women with metastatic breast cancer (MBC). Ultimately,
      however, inevitable intrinsic or acquired resistance to chemotherapy limits
      treatment options. The epothilones, a novel class of microtubule-stabilizing
      agents that have incomplete cross-resistance with taxanes and are less
      susceptible to common mechanisms of resistance, have demonstrated activity in
      breast cancer. Ixabepilone, the best studied epothilone to date, has been
      approved for use as a single agent or in combination with capecitabine in
      anthracycline- and taxanepretreated or refractory MBC. Ixabepilone is relatively
      well tolerated, with the most common side effects being peripheral neuropathy and
      neutropenia. Other epothilones such as KOS-862, patupilone, ZK-EPO, BMS-310705,
      and KOS-1584 are being evaluated as therapy for patients with breast cancer, with
      promising preliminary data. Ongoing research aims to define and optimize the
      efficacy of the epothilones in an attempt to improve the quality of life and
      overall survival of individuals with breast cancer.

PMID- 19158038
TI  - Basal and triple-negative breast cancers: impact on clinical decision-making and
      novel therapeutic options.
AB  - Since the first application of gene expression profiling to breast cancer almost
      a decade ago, the molecular subtyping of breast cancer has advanced rapidly from
      a novel concept to a clinically valuable prognostic, and possibly predictive,
      classification. This review summarizes the definition of the basal and related
      triplenegative subtypes of breast cancer, their clinical associations, and effect
      on outcome and treatment decision- making. Particular emphasis is placed on the
      clinical implications of basal breast cancer and potential therapeutic options
      available to oncologists.

PMID- 19158039
TI  - New understanding of the role of anthracyclines in early-stage breast cancer:
      patient selection considerations.
AB  - In the past decade, a considerable effort has been made to identify molecular
      markers that predict anthracycline activity. A number of retrospective studies
      that evaluated the clinical activity of anthracyclines according to HER2 status
      suggested that the additional benefit of these agents, as compared with non
      anthracycline- based chemotherapy, is confined to HER2-positive tumors. More
      recently, 2 meta-analyses, based on abstracted data, have reinforced this
      concept, challenging the use of adjuvant anthracyclines in patients with HER2
      negative tumors. Additional data suggested that patients who derive the largest
      clinical benefit from anthracycline-based chemotherapy have TOP2A gene-amplified
      tumors. The last hypothesis is based on the fact that topoisomerase IIalpha
      protein is the molecular target of Topo II inhibitors such as anthracyclines. The
      TOP2A gene is located on chromosome 17q12-17q21, next to the HER2/neu gene. TOP2A
      gene aberrations (amplifications or deletions) are more frequent in HER2/neu
      amplified than in HER2/neu-nonamplified tumors. Approximately 35% and 25% of
      HER2/neu-amplified tumors carry TOP2A gene amplifications and deletions,
      respectively; however, although TOP2A gene aberrations are detected most
      frequently in HER2- amplified tumors, topoisomerase IIalpha protein
      overexpression (largely regulated by proliferation signals) and DNA repair
      dysfunctions are observed in different breast cancer subtypes, independent of
      HER2 status. This finding suggests that hypersensitivity to anthracyclines might
      not be confined to HER2-positive tumors, and as a consequence, some patients with
      HER2-negative disease also could derive clinically relevant benefit from these
      compounds.

PMID- 19158040
TI  - Applying Resource Utilization Groups (RUG-III) in Hong Kong nursing homes.
AB  - Resource Utilization Groups III (RUG-III) is a case-mix system developed in the
      United States for categorization of nursing home residents and the financing of
      residential care services. In Hong Kong, RUG-III is based on several board groups
      of residents. The aim of this study was to examine the reliability and validity
      of the RUG-III in Hong Kong nursing homes. A cross-sectional survey was conducted
      in seven residential facilities operated by one agency. Residents ( N = 1,127)
      were assessed by the Minimum Data Set (MDS) and nursing as well as auxiliary
      staff care times were recorded within 2 weeks before or after the completion of
      MDS assessment. Forty-five out 1,127 residents were re-interviewed by an
      independent assessor to assess the inter-rater reliability. The inter-rater
      reliability of MDS assessment was excellent (kappa = 0.76) and the original RUG
      III accounted for about 30 per cent of nursing staff time. Results provide
      preliminary evidence to support that RUG-III is a reliable and valid case-mix
      system for Hong Kong nursing homes, but future studies must be explored to reduce
      the variance of resource use explained by this case-mix system.

PMID- 19158041
TI  - [Between family and formal caregivers, the desire of the elderly on their desire
      to receive assistance].
AB  - In response to the contradictions appearing between, on the one hand, government
      promotion of family caregiving for elderly parents and, on the other, the rise of
      autonomist values (as documented in the literature), we surveyed a number of
      elderly people living with disabilities about the kind of assistance they would
      like to receive. The present qualitative, thematic analysis is based on the
      accounts given by 19 elderly people who receive assistance. The findings show
      that the position of elderly people with respect to their desire to receive (or
      not receive) substantial assistance from their family rests on a set of values,
      wishes, and/or fears - including, particularly, adherence to the value of
      autonomy, the desire to respect freedom (one's own as well as that of others),
      adherence to norms of familial duty, attachment to one's home, the value placed
      on solitude and privacy, and the degree of emotional closeness between the
      elderly and their children. Access to quality formal services also stands out as
      a factor enabling elderly people to actualize the desire for care which they
      elicited within the framework of this analysis.

PMID- 19158042
TI  - Iconic sign comprehension in older adults: the role of cognitive impairment and
      text enhancement.
AB  - Sign comprehension is critical for effective driving, responses to warnings, and
      way-finding. Signs that are poorly comprehended by older people increase accident
      risk and may compromise independence. This study sought to determine whether
      iconic sign comprehension suffers in healthy aging and in the presence of
      cognitive impairment. Additionally, we examined whether the addition of text to
      iconic signage would increase comprehension in older adults. In Experiment 1,
      young adults, healthy older adults, and older adults with varying levels of
      cognitive impairment were asked the meaning of 65 signs used for driving,
      warnings, and way-finding. Healthy older adults were generally good at sign
      comprehension but had difficulty with way-finding signs. Older adults with
      cognitive impairment had poorer sign comprehension overall and particular
      difficulty with way-finding icons and signs that had icons only. In Experiment 2,
      healthy older adults were asked the meaning of signs containing icons only, or
      icons and text. A significant improvement in comprehension was found when text
      was added. An important implication of this work is that the assessment of sign
      comprehension needs to involve a broad and heterogeneous sample of older adults
      reflecting the range of perceptual and cognitive abilities represented in the
      population.

PMID- 19158043
TI  - Family members providing home-based palliative care to older adults: the
      enactment of multiple roles.
AB  - Canadians are experiencing increased life expectancy and chronic illness
      requiring end-of-life care. There is limited research on the multiple roles for
      family members providing home-based palliative care. Based on a larger
      ethnographic study of client-family-provider relationships in home-based
      palliative care, this qualitative secondary analysis explores the enactment of
      multiple roles for family members providing home-based palliative care to seniors
      with advanced cancer. Family members had multiple expectations to provide care
      but felt their expectations of services were unmet. The process of enacting
      multiple roles was depicted by three interrelated themes: balancing, re
      prioritizing, and evolving. Positive and negative health responses resulted from
      attempts to minimize personal health while simultaneously maintaining health.
      "True" family-centred care was found to be lacking, but should be a goal of
      health professionals involved in end-of-life care.

PMID- 19158044
TI  - [Health in peril: repercussions of ageism on the psychological disengagement of
      male nurses aged 45 years and older].
AB  - These two studies are designed to evaluate the reactions of male nurses aged 45
      years and older toward ageism. The goal of the first study is to test the
      prestigious work domain model of psychological disengagement resulting from a
      previous study conducted among female nurses. This model has been confirmed
      through path analyses conducted on a sample of 236 male nurse technicians; by the
      same token, it has been shown to apply in the case of lower-status employees
      working in a prestigious field. In particular, the more a male nurse aged 45 and
      older experiences relative personal deprivation, the more he discredits feedback
      from his co-workers and superiors; such discrediting, in turn, leads to
      devaluation of the domain of work, which in turn lowers self-esteem. The goal of
      the second study is three-fold, namely: (a) testing the disengagement model among
      419 male nurse clinicians; (b) extending this model through the addition of
      ageist communication as a variable triggering personal relative deprivation; and
      (c) constructing a scale of ageist communication. Path analyses have again
      confirmed that the way a domain is appreciated influences the negative impact
      that devaluation can produce on self-esteem, regardless of the gender or status
      of the employee working in that field. In addition, these results demonstrate the
      central role played by communication in the workplace as a vehicle of ageism and
      as a precursor of ageing employees' discomfort. The discussion covers the
      implications of ageing employees' reactions toward ageism as well as the
      consequences of depreciatory language and exclusionary communication practices in
      the workplace.

PMID- 19158045
TI  - Time for municipal elder rights law: an Anglo-Canadian perspective.
AB  - In an age of globalization and privatization, local governments and
      municipalities are searching to define their social role and place. In an aging
      society such as Canada, arguing that promoting the legal rights of older persons
      should be part of the legal authority of the municipal government is not simple.
      It is easier to abide by the position that, without an efficient centralized
      machinery, social and environmental problems will remain unsolved or unaddressed.
      This article presents a different understanding of the place of municipal
      government in Canada. The goal of this article is to present an original legal
      policy argument: It is time for local communities and local governments in Canada
      to use their legal authorities to enact local bylaws that define and establish
      the rights of their older citizens. The argument maintains that local
      municipalities hold the legal power and the social potential to make a
      significant contribution in the legal sphere for promotion of the rights of older
      people, and that this power has been neglected. The article supports the argument
      on three pillars: (1) an empirical analysis of bylaws in different municipalities
      across Canada; (2) a socio-legal analysis of the advantages of municipal law as a
      tool for social change; (3) a case analysis of a recent municipal legal reform in
      British Columbia.

PMID- 19158046
TI  - Discovery of a human peptide sequence signaling islet neogenesis.
AB  - OBJECTIVE: To identify triggers for islet neogenesis in humans that may lead to
      new treatments that address the underlying mechanism of disease for patients with
      type 1 or type 2 diabetes. METHODS: In an effort to identify bioactive human
      peptide sequences that might trigger islet neogenesis, we evaluated amino acid
      sequences within a variety of mammalian pancreas-specific REG genes. We evaluated
      GenBank, the Basic Local Alignment Search Tool algorithm, and all available
      proteomic databases and developed large-scale protein-to-protein interaction
      maps. Studies of peptides of interest were conducted in human pancreatic ductal
      tissue, followed by investigations in mice with streptozocin-induced diabetes.
      RESULTS: Our team has defined a 14-amino acid bioactive peptide encoded by a
      portion of the human REG3a gene we termed Human proIslet Peptide (HIP), which is
      well conserved among many mammals. Treatment of human pancreatic ductal tissue
      with HIP stimulated the production of insulin. In diabetic mice, administration
      of HIP improved glycemic control and significantly increased islet number.
      Bioinformatics analysis, coupled with biochemical interaction studies in a human
      pancreatic cell line, identified the human exostoses-like protein 3 (EXTL3) as a
      HIP-binding protein. HIP enhanced EXTL3 translocation from the membrane to the
      nucleus, in support of a model whereby EXTL3 mediates HIP signaling for islet
      neogenesis. CONCLUSION: Our data suggest that HIP may be a potential stimulus for
      islet neogenesis and that the differentiation of new islets is a process distinct
      from beta cell proliferation within existing islets. Human clinical trials are
      soon to commence to determine the effect of HIP on generating new islets from
      one's own pancreatic progenitor cells.

PMID- 19158048
TI  - Analysis of guidelines for basal-bolus insulin dosing: basal insulin, correction
      factor, and carbohydrate-to-insulin ratio.
AB  - OBJECTIVE: To analyze and compare the underlying mathematical models for basal
      bolus insulin-dosing guidelines in patients with type 1 diabetes in a
      retrospective controlled study. METHODS: Algebraic model-development yielded
      several systems of models with unknown constants, including 3 systems currently
      in use. These systems were compared for logic and consistency. One of these
      systems was the accurate insulin management (AIM) system, which we developed in
      the setting of our large endocrine practice. Our database consisted of
      retrospective clinical records for a 7-month period. During this time, correction
      factor (CF), carbohydrate-to-insulin ratio (CIR), and basal insulin were being
      adjusted incrementally by titration. The variables studied were height, body
      weight in pounds (BWlb), CF, CIR, hemoglobin A1c (A1C), basal insulin, and 6-day
      mean total daily dose of insulin (TDD). The values of the variables used in the
      study were those determined on arrival of the patients at the office. The last 6
      TDDs were entered into the database, and the mean was calculated by formulas
      within the database. We sorted our database into 2 groups, a well-controlled test
      group (n = 167; A1C <or=7%, time on pump >180 days, no severe hypoglycemic events
      since the last office visit, and C-peptide level <or=0.5 ng/mL) and a control
      group with poor control (n = 209; A1C >7% or time on pump <180 days). We obtained
      one office visit per patient, as follows: from the test group, we chose the visit
      with the lowest A1C value; from the control group, we chose one visit by use of a
      computer's random number generator. A significant difference was demonstrated
      between the correlation constants of the test group versus the control group by
      performing T tests between the means and F tests between the standard deviations.
      The least squares estimates of the correlation constants from the test group were
      recommended in the guidelines, in place of the means, to gain accuracy. By these
      methods, the guidelines used by the patients with good glycemic control are made
      available for all patients. RESULTS: With use of the AIM system, the TDD for
      continuous subcutaneous insulin infusion = 0.24 * BWlb; basal insulin = 0.47 *
      TDD; CF = 1,700/TDD; and CIR = 2.8 * BWlb/TDD. CONCLUSION: Three mathematical
      models for CIR are presented, with a rationale for supporting one of them (the
      AIM model). This model, together with 3 related AIM models, when provided with
      statistically correlated constants, constitutes the AIM system of guidelines, a
      consistent and convenient means of estimating insulin-dosing variables for
      patients with type 1 diabetes.

PMID- 19158047
TI  - Risk of cardiovascular events in mothers of women with polycystic ovary syndrome.
AB  - OBJECTIVE: To assess the prevalence of cardiovascular events in an older
      population of women with polycystic ovary syndrome (PCOS). METHODS: We took
      advantage of the high heritability of PCOS and determined the probable PCOS
      status of mothers of women with PCOS. The prevalence of cardiovascular events was
      then determined in these mothers with and without PCOS. In a single endocrine
      clinic, 308 women with PCOS were interviewed about their mothers' medical
      history, and the mothers themselves were interviewed if available. The interview
      addressed menstrual history, fertility, clinical signs of hyperandrogenism, age
      at incident cardiovascular event, and age at death as reported by daughters.
      Presence of PCOS in the mothers was defined as a history of infertility,
      irregular menses, or clinical signs of hyperandrogenism. A cardiovascular event
      was defined as fatal or nonfatal myocardial infarction, any coronary
      intervention, angina necessitating emergency department visits, or a
      cerebrovascular event. RESULTS: The mothers were predominantly post-menopausal.
      Among 182 interviewed (n = 157) or deceased (n = 25) mothers, 59 had probable
      PCOS. Cardiovascular events were more common (P = .011) among mothers with PCOS
      (11 of 59 or 18.6%) than among non-PCOS mothers (5 of 123 or 4.1%). After
      adjustments were made for age and race, probable PCOS was an independent
      predictor of cardiovascular events (odds ratio, 5.41; 95% confidence interval,
      1.78 to 16.40). Cardiovascular events occurred at an early age in mothers of
      women with PCOS, particularly mothers with probable PCOS themselves. CONCLUSION:
      PCOS-affected mothers of women with PCOS have a higher risk for cardiovascular
      events in comparison with non-PCOS mothers, and cardiovascular events appear to
      occur at an earlier than expected age in mothers with PCOS.

PMID- 19158049
TI  - Correlation between bone markers and bone mineral density in postmenopausal women
      with osteoporosis.
AB  - OBJECTIVE: To study the relationship between bone markers and bone mineral
      density (BMD) in an effort to identify their utility in postmenopausal women with
      osteoporosis. METHODS: Eighty-two consecutive postmenopausal women with untreated
      osteoporosis were included in the study. Forearm, spinal, and femoral BMD by dual
      energy x-ray absorptiometry and markers of bone formation (serum osteocalcin and
      bone-specific alkaline phosphatase) and bone resorption (urinary free
      deoxypyridinoline) were measured in all patients. Patients with low serum vitamin
      D levels, secondary osteoporosis, or clinically significant systemic disease were
      excluded from the study. The patients were classified on the basis of BMD of the
      lumbar spine into the following 3 groups: mild (n = 23) (T score -2.5 through 
      3), moderate (n = 42) (T score -3.1 through -4), or severe (n = 17) (T score <or=
      4.1) osteoporosis. One-way analysis of variance and Pearson correlation were used
      for statistical analysis, with a P value <.05 being considered significant.
      RESULTS: Serum osteocalcin was significantly different among the 3 study groups
      (4.1 +/- 2.7, 4.5 +/- 3.1, and 6.7 +/- 5.6 ng/mL, respectively; P = .0349) and
      had a significant negative correlation with BMD (r2 = -0.0779; P = .0168). Other
      bone markers such as bone-specific alkaline phosphatase and urinary free
      deoxypyridinoline did not correlate with the underlying BMD. CONCLUSION: In our
      study, osteocalcin was significantly correlated with BMD in postmenopausal women
      with osteoporosis. Other bone markers did not correlate with BMD. Further large
      scale population data and analyses are needed to confirm these findings.

PMID- 19158050
TI  - Expression analysis of fibroblast growth factor-23, matrix extracellular
      phosphoglycoprotein, secreted frizzled-related protein-4, and fibroblast growth
      factor-7: identification of fibroblast growth factor-23 and matrix extracellular
      phosphoglycoprotein as major factors involved in tumor-induced osteomalacia.
AB  - OBJECTIVE: To evaluate the expression of various phosphaturic factors in the
      tumor of a patient with tumor-induced osteomalacia (TIO) and to analyze serum
      levels of fibroblast growth factor (FGF)-23 in TIO and healthy subjects. METHODS:
      We measured serum FGF-23 levels in 2 patients with TIO and 6 healthy volunteers.
      Expression of FGF-23, matrix extracellular phosphoglycoprotein (MEPE), FGF-7, and
      secreted frizzled-related protein-4 (sFRP-4) was analyzed in a hemangiopericytoma
      from a patient with TIO, in a hemangiopericytoma from a patient without TIO, and
      in various control cell lines. RESULTS: Serum FGF-23 levels were substantially
      higher in patients with TIO in comparison with those in healthy control subjects
      and normalized with successful resection of the tumor. Tissue expression analysis
      showed preferential expression of FGF-23 and MEPE in TIO-related
      hemangiopericytoma, whereas FGF-7 and sFRP-4 were widely expressed in all studied
      cell lines and tissues. CONCLUSION: These results support the use of FGF-23
      measurements for the diagnosis and follow-up of patients with TIO. In addition,
      the specific expression of FGF-23 and MEPE in the TIO-associated tumor suggests
      an important role of these two phosphatonins in the pathogenesis of TIO. Because
      of the limited number of patients in our report, further studies are needed to
      clarify the role of different phosphatonins in the development of the clinical
      features of TIO.

PMID- 19158051
TI  - Glycostator: a novel technology to summarize blood glucose control in patients
      with diabetes mellitus.
AB  - BACKGROUND: Glycostator is a diabetes management software package consisting of 3
      indicators-"time-averaged glucose (TAG)," "virtual A1c (VA1c)," and "lability
      index"-all devised for statistical manipulation of capillary glucose data and
      assessment of overall glycemic control. The TAG approximates the average value of
      the function of blood glucose versus time, adding the element of time to the
      computation of the mean glucose value. It mitigates the major pitfall of the
      arithmetical averaging methods currently available in glucose-monitoring devices:
      bias toward glycemic extremes. With use of the TAG value and a linear function,
      Glycostator calculates VA1c, a statistical emulation of the laboratory hemoglobin
      A1c (HgbA1c). METHODS: We examined the relationship between Glycostator
      calculated VA1c and laboratory-determined HgbA1c in 57 patients. RESULTS:
      Glycostator VA1c results were within 15% of concomitant laboratory HgbA1c values
      in 82% of the patients studied. Further analysis revealed that 60 to 90 days of
      testing and an average of 3 or more finger-stick glucose tests per day optimized
      the accuracy of the VA1c as a predictor of HgbA1c (91% of these patients' VA1c
      values were within 15% of the concomitant HgbA1c laboratory value). CONCLUSION:
      In patients who test blood glucose frequently, VA1c complements HgbA1c as a
      measure of overall glucose control and has the advantage of being updated after
      each blood glucose test for patient and physician feedback. Glycostator
      parameters are calculated by using recurrence relation algorithms that can be
      easily implemented on currently available blood glucose monitors.

PMID- 19158052
TI  - Prevalence of reproductive abnormalities among women with familial partial
      lipodystrophy.
AB  - OBJECTIVE: To compare the risk of having polycystic ovary syndrome (PCOS) or
      ovarian cysts among women with genetically confirmed familial partial
      lipodystrophy (FPLD) with that in the general population of healthy women.
      METHODS: Twenty-five women with FPLD who were 18 to 80 years old were interviewed
      regarding a history of PCOS or ovarian cysts (composite primary outcome) as well
      as for secondary outcomes of interest including menstrual irregularities,
      hirsutism, gynecologic surgical procedures, and fertility or obstetric
      complications. From the 2005 National Ambulatory Medical Care Survey, 3,326
      women, aged 18 to 80 years (control subjects), were assessed for the presence of
      the primary outcome based on appropriate International Classification of
      Diseases, Ninth Revision, Clinical Modification codes. RESULTS: Four of the 25
      patients with FPLD (16%) had a history of PCOS or ovarian cysts, in comparison
      with 14 of the 3,326 control subjects (0.42%), resulting in an age- and body mass
      index-adjusted odds ratio of 40.6 (95% confidence interval, 12.1 to 136.7;
      P<.0001) among the patients with FPLD. Furthermore, 5 women with FPLD (20%)
      required at least 1 oophorectomy during their lifetime, and 6 (24%) had had
      hysterectomies at a young age (<or=55 years). CONCLUSION: Women with genetically
      confirmed FPLD have an increased risk for PCOS and ovarian cysts, as well as
      early hysterectomies, in comparison with the general population. Therefore,
      timely involvement of gynecologists in the care of these patients is warranted.

PMID- 19158053
TI  - Distal renal tubular acidosis due to primary hyperparathyroidism.
AB  - OBJECTIVE: To present 4 cases of distal renal tubular acidosis (RTA) in patients
      with primary hyperparathyroidism (PHPT) and discuss their possible
      etiopathogenetic correlation. METHODS: We diagnosed distal RTA in 4 patients with
      symptomatic primary PHPT on the basis of the baseline biochemical variables and
      the results of the ammonium chloride loading test. Complete resolution of distal
      RTA was documented after surgical cure of PHPT by removal of a parathyroid
      adenoma. RESULTS: All our patients presented with symptomatic bone disease and
      metabolic myopathy. One patient presented with recurrent renal stones.
      Inappropriately alkaline fasting urine (pH >5.5) in association with a normal
      anion gap metabolic acidosis suggested the diagnosis of distal RTA. All cases
      were confirmed by an ammonium chloride loading test. Three patients responded to
      surgical cure of PHPT by normalization of the acid-base status. CONCLUSION:
      Hypercalciuria in PHPT can lead to nephrocalcinosis and renal tubular
      dysfunction, which manifests as distal RTA. Cure of distal RTA after surgical
      treatment of PHPT establishes PHPT as the primary cause of distal RTA in these
      cases.

PMID- 19158054
TI  - Catecholamine-induced cardiomyopathy.
AB  - OBJECTIVE: To review the pathogenesis as well as the clinical and laboratory
      features of catecholamine-induced cardiomyopathy associated with pheochromocytoma
      and other disorders and discuss the various treatment options available. METHODS:
      Materials used for this article were identified through MEDLINE, PubMed, and
      Google Scholar searches of the relevant literature from 1955 to the present.
      RESULTS: Catecholamines and their oxidation products cause a direct toxic effect
      on the myocardium. Catecholamines also exert a receptor-mediated effect on the
      myocardium. Catecholamine-mediated myocardial stunning has been implicated in the
      pathogenesis of stress-induced cardiomyopathy. Biopsy of the myocardium in
      patients with pheochromocytoma or those with stress-induced cardiomyopathy shows
      similar pathologic findings. The clinical features in pheochromocytoma-related
      cardiomyopathy include hypertension, dilated or hypertrophic cardiomyopathy,
      pulmonary edema due to cardiogenic and noncardiogenic factors, cardiac
      arrhythmias, and even cardiac arrest. Stress-related cardiomyopathy such as
      takotsubo cardiomyopathy occurs primarily in postmenopausal women. These patients
      may present with clinical features suggestive of an acute myocardial infarction
      or a hemodynamically compromised state. The definitive management of
      cardiomyopathy associated with pheochromocytoma includes medical treatment with
      alpha-adrenergic blockade, possibly along with angiotensin converting enzyme
      blockers and beta1-adrenergic receptor blockers, followed by excision of the
      tumor. Stress-induced cardiomyopathy is usually self-limiting; patients may
      require support with nonadrenergic inotropes. CONCLUSION: Recognition of
      catecholamine-induced cardiomyopathy, especially in patients with
      pheochromocytoma, before surgical treatment is important to minimize morbidity
      and mortality.

PMID- 19158055
TI  - Bisphosphonate-associated osteomyelitis of the jaw: guidelines for practicing
      clinicians.
AB  - OBJECTIVE: To evaluate the literature and discuss the risk factors, mechanisms,
      pathophysiologic aspects, and recommended management of bisphosphonate-associated
      osteomyelitis of the jaw (BAOMJ). METHODS: More than 350 published articles, case
      reports mentioning BAOMJ, and independent histology slides from BAOMJ lesions
      were reviewed critically. The most pertinent publications are cited and
      discussed. RESULTS: The incidence of BAOMJ increases after extraction of teeth,
      dentoalveolar surgical procedures, or recent oral trauma leading to exposed
      maxillary or mandibular bone. Contributory factors include poor oral hygiene,
      oral infections, periodontal disease; recent or ongoing corticosteroid
      administration or chemotherapy; compromised immune status; diabetes or vascular
      insufficiency; old age; chronic diseases; and malignancies. On average, 1 of
      every 100,000 patients treated with bisphosphonates orally for osteoporosis or
      Paget disease of bone may develop BAOMJ-like lesions. Patients with cancer often
      receive bisphosphonate doses 10 times or higher, and also more frequently, than
      those used in patients with osteoporosis or Paget disease of bone. Therefore,
      greater frequency of administration of bisphosphonates, higher dosages, and
      prolonged use (that is, for more than 2 years) are likely to be factors
      triggering BAOMJ. CONCLUSION: The association of bisphosphonate therapy with
      BAOMJ is rare in noncancer patients and is likely to be a class effect that may
      occur with use of any bisphosphonate. Whether patients with cancer require such a
      high frequency of intravenously administered bisphosphonates needs to be
      investigated. Following established guidelines can decrease the risks of BAOMJ in
      vulnerable patients. Rather than necrotic bone, current evidence supports an
      infectious and perhaps immunologic underlying cause for BAOMJ. The estimated
      incidence of BAOMJ among noncancer patients receiving bisphosphonates is about
      0.001%, whereas among patients with cancer receiving intravenous bisphosphonate
      therapy the incidence is between 0.5% and 4%, depending on the dose, frequency,
      and duration of therapy (on average, approximately 2%). Nevertheless, the
      benefits of bisphosphonates far outweigh the risks.

PMID- 19158056
TI  - Cystic fibrosis-related diabetes mellitus: etiology, evaluation, and management.
AB  - OBJECTIVE: To review the pathophysiology, diagnosis, and management of cystic
      fibrosis-related diabetes mellitus (CFRD). METHODS: We performed a MEDLINE search
      of the literature, using the search terms "cystic fibrosis-related diabetes,
      "CFRD," and "cystic fibrosis and diabetes," to identify pertinent articles
      available in English. RESULTS: In patients with cystic fibrosis (CF), CFRD is a
      major cause for an accelerated decline in health. It is the result of multiple
      pathophysiologic mechanisms, including destruction of pancreatic islet cells,
      impaired hepatic response to the antigluconeogenic effects of insulin, and
      impaired insulin sensitivity. Nutritional management and adequate caloric intake
      are paramount to successful management of CF. Although insulin remains the
      standard of care for treating CFRD in conjunction with fasting hyperglycemia, a
      small but growing body of literature supports the use of oral therapies. In this
      article, we discuss the benefits of and possible adverse reactions to the various
      classes of oral and injectable agents used in the treatment of diabetes mellitus,
      with special attention to the population of patients with CF. CONCLUSION: Orally
      administered agents can have a role in the treatment of CFRD. Further study is
      needed to determine the optimal combination of therapeutic modalities for CFRD.

PMID- 19158057
TI  - Thyroid hormone therapy is not indicated in the majority of patients with the
      sick euthyroid syndrome.

PMID- 19158058
TI  - Vitamin D toxicity: caveat emptor.

PMID- 19158059
TI  - Visual vignette.

PMID- 19158060
TI  - Visual vignette.

PMID- 19158061
TI  - Functional restoration for the stroke survivor: informing the efforts of
      engineers.
AB  - As bioengineers begin to notice the importance of therapy in the recovery from
      stroke and other brain injuries, new technologies will be increasingly conceived,
      adapted, and designed to improve the patient's road to recovery. What is clear
      from engineering history, however, is that the best engineering efforts are often
      built on strong scientific foundations. In an effort to inform engineers with the
      necessary background on cutting edge research in the field of stroke and motor
      recovery, this article summarizes the views of several experts in the field as a
      result of a workshop held in 2006 on the topic. Here we elaborate on several
      areas relevant to this goal, including the pathophysiology of stroke and stroke
      recovery, the biomechanics, the secondary peripheral changes in muscle and other
      tissue, and the results of neuroimaging studies. One conclusion is that the
      current state of knowledge is now ripe for research using machines but that
      highly sophisticated robotic devices may not yet be needed. Instead, what may be
      needed is basic evidence that shows a difference in one therapeutic strategy over
      another.

PMID- 19158063
TI  - Protocol evaluation for effective music therapy for persons with nonfluent
      aphasia.
AB  - Although the notion of the language specificity of neural correlates has been
      widely accepted in the past (e.g., lefthemispheric dominance including Broca's
      and Wernike's area, N400 ERP component of semantic processing, and the P600 ERP
      component of syntactic processing, etc.), recent studies have shown that music
      and language share some important neurological aspects in their processing, both
      involving bilateral hemispheric activities. In line with this are the frequent
      behavioral clinical observations that persons with aphasia show improved
      articulation and prosody of speech in musically assisted phrases. Connecting
      recent neurological findings with clinical observations would not only inform
      clinical practice but would enhance understanding of the neurological mechanisms
      involved in the processing of speech/language and music. This article presents a
      music therapy treatment protocol study of 7 nonfluent patients with aphasia. The
      data and findings are discussed with regard to some of the recent focuses and
      issues addressed in the experimental studies using cognitive-behavioral,
      electrophysiological, and brain-imaging techniques.

PMID- 19158062
TI  - Novel technology for treating individuals with aphasia and concomitant cognitive
      deficits.
AB  - PURPOSE: This article describes three individuals with aphasia and concomitant
      cognitive deficits who used state-of-theart computer software for training
      conversational scripts. METHOD: Participants were assessed before and after 9
      weeks of a computer script training program. For each participant, three
      individualized scripts were developed, recorded on the software, and practiced
      sequentially at home. Weekly meetings with the speech-language pathologist
      occurred to monitor practice and assess progress. Baseline and posttreatment
      scripts were audiotaped, transcribed, and compared to the target scripts for
      content, grammatical productivity, and rate of production of script-related
      words. Interviews were conducted at the conclusion of treatment. RESULTS: There
      was great variability in improvements across scripts, with two participants
      improving on two of their three scripts in measures of content, grammatical
      productivity, and rate of production of scriptrelated words. One participant
      gained more than 5 points on the Aphasia Quotient of the Western Aphasia Battery.
      Five positive themes were consistently identified from exit interviews: increased
      verbal communication, improvements in other modalities and situations,
      communication changes noticed by others, increased confidence, and satisfaction
      with the software. CONCLUSION: Computer-based script training potentially may be
      an effective intervention for persons with chronic aphasia and concomitant
      cognitive deficits.

PMID- 19158064
TI  - Application of neuroscience to technology in stroke rehabilitation.
AB  - The past decade has seen remarkable advances in our understanding of mechanisms
      that drive functional neuroplastic change after brain injury and the mirror
      neuron system that appears essential for language learning and communicative
      interaction. This article describes five neuroscience-based interventions
      available for clinical practice, with a discussion of the potential value of
      mirror neurons in stroke rehabilitation. Case-study data on three adults with
      aphasia who received various combinations of neuroscience-derived technological
      interventions are provided to inform the clinician of the potential advantages of
      technology as an adjunct to, not a substitution for, conventional therapeutic
      intervention.

PMID- 19158065
TI  - Technology applications at the Adler aphasia center.
AB  - This article describes a life participation approach to computer instruction for
      adults with aphasia and their caregivers. In contrast with the application of
      computer programs as a component of language rehabilitation with specific outcome
      goals, the approach described here is designed to improve overall communication
      skills, heighten self-confidence, and re-engage individuals with aphasia in
      social and community activities. The technology use described includes relevant
      activities for language stimulation, e-mail correspondence, and productivity
      projects, all selected by the individuals with aphasia and their caregivers. Each
      technology offering is described in terms of its use and consideration for future
      applications.

PMID- 19158066
TI  - Hemiparetic optimal practice and evaluation (H.O.P.E.) for the stroke survivor
      with very low hand function.
AB  - PURPOSE: The purpose of this study is to describe an approach that may benefit
      persons with severe hemiparesis following stroke. METHOD: The subjects were 3
      stroke survivors who had experienced a stroke that left their dominant right
      extremity severely disabled (mean age 43 years, mean time since stroke 26.6
      months, mean Fugl-Meyer UE motor score 14.3/66). A multiple baseline,
      preintervention-postintervention case series design was used. The intervention
      consisted of structured whole body, increased intensity, activity-dependent
      practice strategy, with 3 to 5 sessions lasting for more than 3 hours per day,
      for 1-5 weeks for an average of 170 hours of therapy over 2.5 years. Subjects
      completed therapies such as body weight-supported treadmill training, overground
      multidirectional gait training, balance retraining, upper extremity functional
      activity, and trunk and extremity mobility. RESULTS: The subjects experienced
      decreased fall risk (mean Timed Up and Go [TUG] scores decreased from 14.9 s to
      6.8 s) and improved community safety (mean speed of gait in 10 m improved from
      18.3 s to 8.3 s) and decreased impairment level as measured by the Fugl-Meyer
      Assessment (FMA: mean UE motor score from 14.3/66 to 53/66). Finally, subjects
      demonstrated an increase in their hemiparetic UE functional ability (mean amount
      of tasks completed in the Wolf Motor Function Test [WMFT] from 3.6/15 tasks to
      15/15 tasks) following the intervention. CONCLUSION: The findings indicate that
      hemiparetic optimal practice and evaluation (H.O.P.E) rehabilitation led to a
      decrease in the level of impairment along with a corresponding increase in
      function of the severely hemiparetic arm. The outcomes are significant: few
      treatment approaches have demonstrated an increase in the function of the
      severely affected arm in this population.

PMID- 19158067
TI  - Differences in the experiences and support needs of family caregivers to stroke
      survivors: does age matter?
AB  - PURPOSE: The rehabilitation stage of a stroke survivor's recovery provides an
      opportunity to prepare family caregivers for the supportive role they will play
      in the community. The goal of this qualitative study was to learn about family
      caregivers' experiences and support needs during the rehabilitation phase to
      inform program development. METHOD: We recruited family caregivers within the
      first 6 months post stroke. Nine caregivers participated in 40- to 60-minute in
      depth qualitative interviews where the personal needs of caregivers were
      illuminated. Data were analyzed using content analysis. RESULTS: An overriding
      theme was differences in personal needs between older and younger caregivers. We
      interviewed five younger caregivers (55 years of age) and four older caregivers
      (>55 years of age). Younger caregivers identified informational support and
      training as important parts of their social support whereas older caregivers did
      not. Younger caregivers were also more likely to complain or criticize the health
      care system and staff than older caregivers. A common theme among older
      caregivers was to focus on the importance of keeping a positive outlook
      throughout the experience. CONCLUSION: Caregiver experiences and support needs
      varied according to age. This suggests that support programs should consider age
      as a factor when tailoring interventions.

PMID- 19158068
TI  - An ankle to computer virtual reality system for improving gait and function in a
      person 9 months poststroke.
AB  - BACKGROUND AND PURPOSE: Repetitive practice improves function and facilitates
      cortical plasticity after stroke. Virtual reality (VR) systems have the potential
      to provide motivating and safe repetitive practice with minimal supervision. The
      purpose of this case study is to look at the effect of a VR system, activated by
      surface electromyography of dorsiflexors and plantarflexors, on gait velocity,
      function, and kinematics. METHOD: The first person randomized to the treatment
      group of a larger study was chosen for this case. She was 51 years old and 9
      months poststroke. She received treatment 3 times per week for 8 weeks. Each 60
      minute session consisted of both structured lower extremity exercise and VR ankle
      activities. RESULTS: After intervention, the subject demonstrated increased gait
      speed and decreased time to perform the modified Emory Functional Ambulation
      Profile. Gait kinematics demonstrated improved ankle motion and plantarflexion
      moments at push off. DISCUSSION: The improved gait speed, possibly due to
      increased ankle plantarflexion motion and moments, resulted in a more normalized
      trailing limb posture. This case study suggests that ankle to computer VR systems
      may help stroke patients improve gait function. This VR system has potential as
      an adjunctive therapy or home program requiring minimal supervision.

PMID- 19158069
TI  - Disability studies in practice: a work in progress.
AB  - Disability studies, a field of critical study that emerged from the disability
      rights movement, challenges the medical domination in the lives of people with
      disabilities and has the potential to transform rehabilitation practice.
      Significant practical and attitudinal barriers exist to changing rehabilitation
      practice. Using a point-counterpoint framework, this article examines some common
      objections to integrating disability studies perspectives into rehabilitation
      practice and provides solutions, strategies, and rationales for a disability
      studies informed practice.

PMID- 19158070
TI  - Memoir of a lost adulthood.

PMID- 19158071
TI  - Self-image and quality of life of dermatology patients.
AB  - OBJECTIVES: The problems of self-image among patients with dermal problems have
      been seldom explored. As dermal diseases detrimentally affect well-being,
      functioning and adaptation of dermatology patients, they may decrease the level
      of self-acceptance. Self-image, on the other hand, may significantly affect the
      own mental health status and quality of life (QoL) in that group of patients. The
      aim of our research was to assess mental health status and quality of life of
      patients with dermal problems in respect of the level of their self-acceptance.
      MATERIALS AND METHODS: The participants were patients of the Occupational
      Diseases Outpatient Clinic and the Occupational and Environmental Allergy Centre
      of the Nofer Institute of Occupational Medicine (NIOM). In total, 112 patients
      were examined, including 37 with diagnosed urticaria, 50 with allergic contact
      dermatitis and 25 with atopic dermatitis. General Health Questionnaire (GHQ) was
      used to assess patients' mental health, a Polish version of Dermatology Life
      Quality Index (DLQI) was employed for the assessment of their life quality, while
      Self-Acceptance Scale (SAS) served to obtain patients' self-image. RESULTS: There
      were statistically significant differences in the assessment of mental health and
      quality of life, depending on the level of self-acceptance. People with high self
      acceptance are characterised by better mental health condition than those with
      low self-acceptance (t=4.8; p=0.00). The patients with negative self-image
      (compared to those with positive self-image) deem also their quality of life to
      be poor (t=3.1; p=0.00). CONCLUSION: A relationship has been found to exist both
      between mental health condition and the subjective assessment of life quality,
      and self-image. Thus, both patient's mental health status and his/her self image
      constitute major determinants of the quality of life that are worth to be
      monitored in dermatology patients. Their treatment procedure should include also
      psychological consulting or psychotherapy.

PMID- 19158072
TI  - Ambient air pollution and daily emergency department visits for ischemic stroke
      in Edmonton, Canada.
AB  - OBJECTIVES: In this report, we examine the associations between emergency
      department (ED) visits for acute ischemic stroke and environmental conditions.
      MATERIALS AND METHODS: The study concerned 10,881 ED visits for acute ischemic
      stroke (ICD-9: 434, 436) recorded at Edmonton hospitals between 1992 and 2002.
      Generalized linear mixed models technique was applied to build the statistical
      models. The logarithm of daily counts of ED visits for stroke was regressed on
      the levels of air pollutants (CO, NO2, SO2, and O3) and two meteorological
      variables. The analyses were performed by (a) age: two age groups were
      distinguished: 20-64 years (n=2873) and 65-100 years (n=8008); (b) season (all
      seasons: January-December, warm: April-September, cold: October-March); and (c)
      gender (both, male, female). RESULTS: The results are reported as an excess risk
      in relation to an increase in the interquartile range (IQR) of the pollutants. In
      the age group 65-100 years, the excess risk for particular pollutants was as
      follows: for NO2-8.2% (95% CI: 0.4-16.7) for both genders, in the warm season;
      for SO2-9.1% (95% CI: 2.2-16.4), for males, in the warm season: for a 1-day
      lagged SO2-6.0% (95% CI: 0.5-11.8), for females, in the cold season. Among the
      patients aged 20-64 years, the excess risk for NO2 was 6.3% (95% CI: 0.2-12.8),
      for both genders, and all seasons; and 13.8% (95% CI: 2.1-26.7), for females, in
      the cold season; for a 1-day lagged O3-17.8% (95% CI: 2.2-35.6), for males, in
      the warm season; for a 1-day lagged SO2-10.3% (95% CI: 0.7-20.9) for females, in
      the cold season. CONCLUSIONS: The findings provide evidence that exposure to air
      pollutants is significantly associated with ED visits for acute ischemic stroke.

PMID- 19158073
TI  - Mammalian heat shock factor 1 is essential for oocyte meiosis and directly
      regulates Hsp90alpha expression.
AB  - Heat shock transcription factor 1 (HSF1) is the main regulator of the stress
      response that triggers the transcription of several genes encoding heat shock
      proteins (Hsps). Hsps act as molecular chaperones involved in protein folding,
      stability, and trafficking. HSF1 is highly expressed in oocytes and Hsf1 knock
      out in mice revealed that in the absence of stress this factor plays an important
      role in female reproduction. We previously reported that Hsf1(-/-) females
      produce oocytes but no viable embryos. Consequently, we asked whether oocytes
      require HSF1 to regulate a particular set of Hsps necessary for them to develop.
      We find that Hsp90alpha (Hspaa1) is the major HSF1-dependent chaperone inasmuch
      as Hsf1 knock-out resulted in Hsp90-depleted oocytes. These oocytes exhibited
      delayed germinal vesicle breakdown (or G(2)/M transition), partial meiosis I
      block, and defective asymmetrical division. To probe the role of Hsp90alpha in
      this meiotic syndrome, we analyzed meiotic maturation in wild-type oocytes
      treated with a specific inhibitor of Hsp90, 17-allylamino-17-demethoxy
      geldanamycin, and observed similar defects. At the molecular level we showed
      that, together with these developmental anomalies, CDK1 and MAPK, key meiotic
      kinases, were significantly disturbed. Thus, our data demonstrate that HSF1 is a
      maternal transcription factor essential for normal progression of meiosis.

PMID- 19158074
TI  - Structure-function relationship of the chloroplastic glutaredoxin S12 with an
      atypical WCSYS active site.
AB  - Glutaredoxins (Grxs) are efficient catalysts for the reduction of mixed
      disulfides in glutathionylated proteins, using glutathione or thioredoxin
      reductases for their regeneration. Using GFP fusion, we have shown that poplar
      GrxS12, which possesses a monothiol (28)WCSYS(32) active site, is localized in
      chloroplasts. In the presence of reduced glutathione, the recombinant protein is
      able to reduce in vitro substrates, such as hydroxyethyldisulfide and
      dehydroascorbate, and to regenerate the glutathionylated glyceraldehyde-3
      phosphate dehydrogenase. Although the protein possesses two conserved cysteines,
      it is functioning through a monothiol mechanism, the conserved C terminus
      cysteine (Cys(87)) being dispensable, since the C87S variant is fully active in
      all activity assays. Biochemical and crystallographic studies revealed that
      Cys(87) exhibits a certain reactivity, since its pK(a) is around 5.6. Coupled
      with thiol titration, fluorescence, and mass spectrometry analyses, the
      resolution of poplar GrxS12 x-ray crystal structure shows that the only oxidation
      state is a glutathionylated derivative of the active site cysteine (Cys(29)) and
      that the enzyme does not form inter- or intramolecular disulfides. Contrary to
      some plant Grxs, GrxS12 does not incorporate an iron-sulfur cluster in its wild
      type form, but when the active site is mutated into YCSYS, it binds a [2Fe-2S]
      cluster, indicating that the single Trp residue prevents this incorporation.

PMID- 19158075
TI  - Differential gene expression in vertebrate embryos.

PMID- 19158076
TI  - Structural and functional studies of archaeal viruses.
AB  - Viruses populate virtually every ecosystem on the planet, including the extreme
      acidic, thermal, and saline environments where archaeal organisms can dominate.
      For example, recent studies have identified crenarchaeal viruses in the hot
      springs of Yellowstone National Park and other high temperature environments
      worldwide. These viruses are often morphologically and genetically unique, with
      genomes that show little similarity to genes of known function, complicating
      efforts to understand their viral life cycles. Here, we review progress in
      understanding these fascinating viruses at the molecular level and the
      evolutionary insights coming from these studies.

PMID- 19158077
TI  - RGC-32 mediates transforming growth factor-beta-induced epithelial-mesenchymal
      transition in human renal proximal tubular cells.
AB  - Epithelial-mesenchymal transition (EMT) occurs in several disease states,
      including renal fibrosis and carcinogenesis. Myofibroblasts produced from EMT of
      renal tubular cells are responsible for the deposition of extracellular matrix
      components in a large portion of renal interstitial fibrosis. Transforming growth
      factor-beta (TGF-beta) plays an essential role in the EMT of renal tubular cells,
      but the molecular mechanism governing this process remains largely unknown. In
      this study, we found that RGC-32 (response gene to complement 32) is critical for
      TGF-beta-induced EMT of human renal proximal tubular cells (HPTCs). RGC-32 is not
      normally expressed in the HPTCs. However, TGF-beta stimulation markedly activates
      RGC-32 while inducing an EMT, as shown by the induction of smooth muscle alpha
      actin (alpha-SMA) and extracellular matrix proteins collagen I and fibronectin,
      as well as the reduction of epithelial marker E-cadherin. TGF-beta function is
      mediated by several signaling pathways, but RGC-32 expression in HPTCs appears to
      be mainly regulated by Smad. Functionally, RGC-32 appears to mediate TGF-beta
      induced EMT of HPTCs. Blockage of RGC-32 using short hairpin interfering RNA
      significantly inhibits TGF-beta induction of myofibroblast marker gene alpha-SMA
      while repressing the expression of E-cadherin. In contrast, overexpression of RGC
      32 induces alpha-SMA expression while restoring E-cadherin. RGC-32 also inhibits
      the expression of another adherens junction protein, N-cadherin, suggesting that
      RGC-32 alone induces the phenotypic conversion of renal epithelial cells to
      myofibroblasts. Additional studies show that RGC-32 stimulates the production of
      extracellular matrix components fibronectin and collagen I. Mechanistically, RGC
      32 induces EMT via the activation of other transcription factors such as Snail
      and Slug. RGC-32 knockdown inhibits the expression of Snail and Slug during TGF
      beta-induced EMT. Taken together, our data demonstrate for the first time that
      RGC-32 plays a critical role in TGF-beta-induced EMT of renal tubular cells.

PMID- 19158079
TI  - A Two-amino Acid Mutation Encountered in Duchenne Muscular Dystrophy Decreases
      Stability of the Rod Domain 23 (R23) Spectrin-like Repeat of Dystrophin.
AB  - Lack of functional dystrophin causes severe Duchenne muscular dystrophy. The
      subsarcolemmal location of dystrophin, as well as its association with both
      cytoskeleton and membrane, suggests a role in the mechanical regulation of
      muscular membrane stress. In particular, phenotype rescue in a Duchenne muscular
      dystrophy mice model has shown that some parts of the central rod domain of
      dystrophin, constituted by 24 spectrin-like repeats, are essential. In this
      study, we made use of rare missense pathogenic mutations in the dystrophin gene
      and analyzed the biochemical properties of the isolated repeat 23 bearing single
      or double mutations E2910V and N2912D found in muscle dystrophy with severity
      grading. No dramatic effect on secondary and tertiary structure of the repeat was
      found in mutants compared with wild type as revealed by circular dichroism and
      NMR. Thermal and chemical unfolding data from circular dichroism and tryptophan
      fluorescence show significant decrease of stability for the mutants, and stopped
      flow spectroscopy shows decreased refolding rates. The most deleterious single
      mutation is the N2912D replacement, although we observe additive effects of the
      two mutations on repeat stability. Based on three-dimensional structures built by
      homology molecular modeling, we discuss the modifications of the mutation-induced
      repeat stability. We conclude that the main forces involved in repeat stability
      are electrostatic inter-helix interactions that are disrupted following
      mutations. This study represents the first analysis at the protein level of the
      consequences of missense mutations in the human dystrophin rod domain. Our
      results suggest that it may participate in mechanical weakening of dystrophin
      deficient muscle.

PMID- 19158078
TI  - Control of rapsyn stability by the CUL-3-containing E3 ligase complex.
AB  - Rapsyn is a postsynaptic protein required for clustering of nicotinic
      acetylcholine receptors (nAChRs) at the neuromuscular junction. Here we report
      the mechanism for posttranslational control of rapsyn protein stability. We
      confirmed that C18H9.7-encoded RPY-1 is a rapsyn homolog in Caenorhabditis
      elegans by showing that human rapsyn rescued rpy-1 mutant phenotypes in
      nematodes, as determined by levamisole assays and micropost array behavioral
      assays. We found that RPY-1 was degraded in the absence of functional UNC-29, a
      non-alpha subunit of the receptor, in an allele-specific manner, but not in the
      absence of other receptor subunits. The cytoplasmic loop of UNC-29 was found to
      be critical for RPY-1 stability. Through RNA interference screening, we found
      that UBC-1, UBC-12, NEDD-8, and RBX-1 were required for degradation of RPY-1. We
      identified cullin (CUL)-3 as a component of E3 ligase and KEL-8 as the substrate
      adaptor of RPY-1. Mammalian rapsyn was ubiquitinated by the CUL3/KLHL8-containing
      E3 ligase in vitro, and the knockdown of KLHL-8, a mammalian KEL-8 homolog,
      inhibited rapsyn ubiquitination in vivo, implying evolutionary conservation of
      the rapsyn stability control machinery. kel-8 suppression and rpy-1
      overexpression in C. elegans produced a phenotype similar to that of a loss-of
      function mutation of rpy-1, suggesting that control of rapsyn abundance is
      important for proper function of the receptor. Our results suggest a link between
      the control of rapsyn abundance and congenital myasthenic syndromes.

PMID- 19158080
TI  - Pneumocystis mediates overexpression of antizyme inhibitor resulting in increased
      polyamine levels and apoptosis in alveolar macrophages.
AB  - Pneumocystis pneumonia (PcP) is the most common opportunistic disease in
      immunocompromised patients. Alveolar macrophages are responsible for the
      clearance of Pneumocystis organisms; however, they undergo a high rate of
      apoptosis during PcP due to increased intracellular polyamine levels. In this
      study, the sources of polyamines and mechanisms of polyamine increase and
      polyamine-induced apoptosis were investigated. The level of ornithine
      decarboxylase (ODC) was elevated in alveolar macrophages, and the number of
      alveolar macrophages that took up exogenous polyamines was increased 20-fold
      during PcP. Monocytes, B lymphocytes, and CD8+ T lymphocytes that were recruited
      into the lung during PcP expressed high levels of ornithine decarboxylase,
      suggesting that these cells are sources of polyamines. Both protein and mRNA
      levels of antizyme inhibitor (AZI) were increased in alveolar macrophages during
      PcP. This AZI overexpression correlated with increased polyamine uptake by
      alveolar macrophages, because AZI expression knockdown decreased the polyamine
      uptake ability of these cells. AZI expression knockdown also decreased the
      apoptosis rate of alveolar macrophages. Pneumocystis organisms and zymosan A were
      found to induce AZI overexpression in alveolar macrophages, suggesting that beta
      glucan, which is the major component of the Pneumocystis cell wall, induces AZI
      overexpression. The levels of mRNA, protein, and activity of polyamine oxidase
      were increased in alveolar macrophages during PcP, indicating that the H(2)O(2)
      generated during polyamine catabolism caused alveolar macrophages to undergo
      apoptosis. Taken together, results of this study indicate that Pneumocystis
      organisms induce AZI overexpression in alveolar macrophages, leading to increased
      polyamine synthesis and uptake and apoptosis rate of these cells.

PMID- 19158081
TI  - Hydroxyurea sensitivity reveals a role for ISC1 in the regulation of G2/M.
AB  - Saccharomyces cerevisiae cells lacking ISC1 (inositol phosphosphingolipase C)
      exhibit sensitivity to genotoxic agents such as methyl methanesulfonate and
      hydroxyurea (HU). Cell cycle analysis by flow cytometry revealed a G(2)/M block
      in isc1Delta cells when treated with methyl methanesulfonate or HU. Further
      investigation revealed that the levels of Cdc28 phosphorylated on Tyr-19, which
      plays an essential role in the regulation of the G(2)/M checkpoint, were higher
      in synchronized and asynchronous cells lacking ISC1 in response to HU. Use of a
      Cdc28-Y19F mutant protected isc1Delta from the G(2)/M block. In wild type cells,
      HU induced a loss of the Swe1p kinase, the enzyme that phosphorylates Cdc28-Tyr
      19, correlating with resumption of the cell cycle. In the isc1Delta cells,
      however, the levels of Swe1p remained at sustained high levels in response to HU.
      Significantly, deletion of SWE1 in an isc1Delta background overcame the G(2)/M
      block in response to HU. The double isc1Delta/swe1Delta mutant also overcame the
      growth defect on HU. Taken together, these findings implicate Isc1p as an
      upstream regulator of Swe1p levels and stability and Cdc28-Tyr-19
      phosphorylation, in effect signaling recovery from the effects of genotoxic
      stress and allowing G(2)/M progression.

PMID- 19158082
TI  - Type I Arginine Methyltransferases PRMT1 and PRMT-3 Act Distributively.
AB  - Asymmetric dimethylation of arginine residues is a common posttranslational
      modification of proteins carried out by type I protein arginine
      methyltransferases, including PRMT1 and -3. We report that the consecutive
      transfer of two methyl groups to a single arginine side chain by PRMT1 and -3
      occurs in a distributive manner, i.e. with intermittent release of the
      monomethylated intermediate. The oligomeric state of PRMTs together with the
      clustering of methylated arginine residues in most proteins carrying this type of
      modification suggests that multiple methyl transfers to a single polypeptide
      chain might proceed in a processive manner by cooperation of multiple active
      sites. However, three different types of experiments provide evidence that the
      reaction is distributive even with substrates containing multiple methyl
      accepting arginines, including one with 13 such residues. PRMT1 also does not
      prefer substrates already containing one or more singly or doubly methylated
      arginine residues. Even though the reaction is distributive, the efficiency of
      methylation of one particular protein strongly depends on the number of methyl
      accepting arginine residues it contains.

PMID- 19158083
TI  - BMP4 mediates oxidative stress-induced retinal pigment epithelial cell senescence
      and is overexpressed in age-related macular degeneration.
AB  - The retinal pigment epithelium is a primary site of pathology in age-related
      macular degeneration. Oxidative stress and senescence are both thought to be
      important mediators of macular degeneration pathogenesis. We demonstrate here
      that bone morphogenetic protein-4 is highly expressed in the retinal pigment
      epithelium and adjacent extracellular matrix of patients with dry age-related
      macular degeneration. In vitro studies revealed that sublethal oxidative stress
      increased bone morphogenetic protein-4 expression in retinal pigment epithelial
      cells, and both bone morphogenetic protein-4 and persistent mild oxidative stress
      can induce retinal pigment epithelial cell senescence through p53-p21(Cip1/WAF1)
      Rb pathway. We further demonstrate that bone morphogenetic protein-4 acts as a
      mediator in oxidative stress-induced senescence and that this mediator function
      is via Smad and the p38 signaling pathway to increase and activate p53 and
      p21(Cip1/WAF1) and decrease phospho-Rb. Oxidative stress-induced senescence can
      be blocked by Chordin-like, an antagonist of bone morphogenetic protein-4, or
      SB203580, a phospho-p38 inhibitor. Our results suggest that oxidative stress and
      bone morphogenetic protein-4 may interact to promote retinal pigment epithelial
      cell senescence and that bone morphogenetic protein-4 may represent a novel
      therapeutic target to inhibit the progressive effects of oxidative stress and
      senescence in dry age-related macular degeneration.

PMID- 19158084
TI  - HDAC6 modulates Hsp90 chaperone activity and regulates activation of aryl
      hydrocarbon receptor signaling.
AB  - The aryl hydrocarbon receptor (AhR), a ligand-activated member of the basic helix
      loop-helix family of transcription factors, binds with high affinity to
      polycyclic aromatic hydrocarbons (PAH) and the environmental toxin 2,3,7,8
      tetrachlorodibenzo-p-dioxin (dioxin). Most of the biochemical, biological, and
      toxicological responses caused by exposure to PAHs and polychlorinated dioxins
      are mediated, at least in part, by the AhR. The AhR is a client protein of Hsp90,
      a molecular chaperone that can be reversibly acetylated with functional
      consequences. The main objective of this study was to determine whether
      modulating Hsp90 acetylation would affect ligand-mediated activation of AhR
      signaling. Trichostatin A and suberoylanilide hydroxamic acid, two broad spectrum
      HDAC inhibitors, blocked PAH and dioxin-mediated induction of CYP1A1 and CYP1B1
      in cell lines derived from the human aerodigestive tract. Silencing HDAC6 or
      treatment with tubacin, a pharmacological inhibitor of HDAC6, also suppressed the
      induction of CYP1A1 and CYP1B1. Inhibiting HDAC6 led to hyperacetylation of Hsp90
      and loss of complex formation with AhR, cochaperone p23, and XAP-2. Inactivation
      or silencing of HDAC6 also led to reduced binding of ligand to the AhR and
      decreased translocation of the AhR from cytosol to nucleus in response to ligand.
      Ligand-induced recruitment of the AhR to the CYP1A1 and CYP1B1 promoters was
      inhibited when HDAC6 was inactivated. Mutation analysis of Hsp90 Lys(294) shows
      that its acetylation status is a strong determinant of interactions with AhR and
      p23 in addition to ligand-mediated activation of AhR signaling. Collectively,
      these results show that HDAC6 activity regulates the acetylation of Hsp90, the
      ability of Hsp90 to chaperone the AhR, and the expression of AhR-dependent genes.
      Given the established link between activation of AhR signaling and xenobiotic
      metabolism, inhibitors of HDAC6 may alter drug or carcinogen metabolism.

PMID- 19158085
TI  - KIF4 mediates anterograde translocation and positioning of ribosomal constituents
      to axons.
AB  - In this study, we have used a combination of biochemical and molecular biology
      techniques to demonstrate that the C-terminal tail domain of KIF4 directly
      interacts with P0, a major protein component of ribosomes. Besides, in dorsal
      root ganglion neurons, KIF4 and P0, as well as other ribosomal constituents,
      colocalize in clusters distributed along axons and neuritic tips. RNA
      interference suppression of KIF4 or expression of KIF4 variants lacking the tail
      domain or mutations of the ATP-binding site result in accumulation of P0 and
      other ribosomal proteins at the cell body and in their disappearance from axons.
      Our results also show one additional function for KIF4 involving an Ezrin-Radixin
      Moesin-like domain in the second coiled-coiled region of KIF4. Expression of a
      KIF4 mutant lacking this domain abolishes the clustering of ribosomal
      constituents and prevents the anterograde translocation of the cell adhesion
      molecule L1. Taken together, the present results suggest that by binding to P0
      through its tail domain and by using its motor activity, KIF4 is involved in the
      anterograde trafficking of ribosomal constituents to axons and that by means of
      its Ezrin-Radixin-Moesin-like domain interacts and transports L1.

PMID- 19158086
TI  - New role of flavin as a general acid-base catalyst with no redox function in type
      2 isopentenyl-diphosphate isomerase.
AB  - Using FMN and a reducing agent such as NAD(P)H, type 2 isopentenyl-diphosphate
      isomerase catalyzes isomerization between isopentenyl diphosphate and
      dimethylallyl diphosphate, both of which are elemental units for the biosynthesis
      of highly diverse isoprenoid compounds. Although the flavin cofactor is expected
      to be integrally involved in catalysis, its exact role remains controversial.
      Here we report the crystal structures of the substrate-free and complex forms of
      type 2 isopentenyl-diphosphate isomerase from the thermoacidophilic archaeon
      Sulfolobus shibatae, not only in the oxidized state but also in the reduced
      state. Based on the active-site structures of the reduced FMN-substrate-enzyme
      ternary complexes, which are in the active state, and on the data from site
      directed mutagenesis at highly conserved charged or polar amino acid residues
      around the active site, we demonstrate that only reduced FMN, not amino acid
      residues, can catalyze proton addition/elimination required for the isomerase
      reaction. This discovery is the first evidence for this long suspected, but
      previously unobserved, role of flavins just as a general acid-base catalyst
      without playing any redox roles, and thereby expands the known functions of these
      versatile coenzymes.

PMID- 19158087
TI  - Source of phosphate in the enzymic reaction as a point of distinction among
      aminoglycoside 2''-phosphotransferases.
AB  - Aminoglycoside 2''-phosphotransferases are clinically important enzymes that
      cause high levels of resistance to aminoglycoside antibiotics by the organisms
      that harbor them. These enzymes phosphorylate aminoglycosides, and the modified
      antibiotics show significant reduction in the binding ability to target the
      bacterial ribosome. This report presents a detailed characterization of the
      antibiotic resistance profile and the aminoglycoside and nucleotide triphosphate
      substrate profiles of four common aminoglycoside 2''-phosphotransferases widely
      distributed in clinically important Gram-positive microorganisms. Although the
      antibiotic resistance phenotypes exhibited by these enzymes are similar, their
      aminoglycoside and nucleotide triphosphate substrate profiles are distinctive.
      Contrary to the dogma that these enzymes use ATP as the source of phosphate in
      their reactions, two of the four aminoglycoside 2'-phosphotransferases utilize
      GTP as the phosphate donor. Of the other two enzymes, one exhibits preference for
      ATP, and the other can utilize either ATP or GTP as nucleotide triphosphate
      substrate. A new nomenclature for these enzymes is put forth that takes into
      account the differences among these enzymes based on their respective substrate
      preferences. These nucleotide triphosphate preferences should have ramifications
      for understanding of the evolution, selection, and dissemination of the genes for
      these important resistance enzymes.

PMID- 19158088
TI  - Protein radicals in fungal versatile peroxidase: catalytic tryptophan radical in
      both compound I and compound II and studies on W164Y, W164H, and W164S variants.
AB  - Lignin-degrading peroxidases, a group of biotechnologically interesting enzymes,
      oxidize high redox potential aromatics via an exposed protein radical. Low
      temperature EPR of Pleurotus eryngii versatile peroxidase (VP) revealed, for the
      first time in a fungal peroxidase, the presence of a tryptophanyl radical in both
      the two-electron (VPI) and the one-electron (VPII) activated forms of the enzyme.
      Site-directed mutagenesis was used to substitute this tryptophan (Trp-164) by
      tyrosine and histidine residues. No changes in the crystal structure were
      observed, indicating that the modified behavior was due exclusively to the
      mutations introduced. EPR revealed the formation of tyrosyl radicals in both VPI
      and VPII of the W164Y variant. However, no protein radical was detected in the
      W164H variant, whose VPI spectrum indicated a porphyrin radical identical to that
      of the inactive W164S variant. Stopped-flow spectrophotometry showed that the
      W164Y mutation reduced 10-fold the apparent second-order rate constant for VPI
      reduction (k(2app)) by veratryl alcohol (VA), when compared with over 50-fold
      reduction in W164S, revealing some catalytic activity of the tyrosine radical.
      Its first-order rate constant (k(2)) was more affected than the dissociation
      constant (K(D)(2)). Moreover, VPII reduction by VA was impaired by the above
      mutations, revealing that the Trp-164 radical was involved in catalysis by both
      VPI and VPII. The low first-order rate constant (k(3)) values were similar for
      the W164Y, W164H, and W164S variants, indicating that the tyrosyl radical in VPII
      was not able to oxidize VA (in contrast with that observed for VPI). VPII self
      reduction was also suppressed, revealing that Trp-164 is involved in this
      autocatalytic process.

PMID- 19158089
TI  - Estrogen Receptor {alpha} Enhances the Rate of Oxidative DNA Damage by Targeting
      an Equine Estrogen Catechol Metabolite to the Nucleus.
AB  - Exposure to estrogens increases the risk of breast and endometrial cancer. It is
      proposed that the estrogen receptor (ER) may contribute to estrogen
      carcinogenesis by transduction of the hormonal signal and as a "Trojan horse"
      concentrating genotoxic estrogen metabolites in the nucleus to complex with DNA,
      enhancing DNA damage. 4-Hydroxyequilenin (4-OHEN), the major catechol metabolite
      of equine estrogens present in estrogen replacement formulations, autoxidizes to
      a redox-cycling quinone that has been shown to cause DNA damage. 4-OHEN was found
      to be an estrogen of nanomolar potency in cell culture using a luciferase
      reporter assay and, using a chromatin immunoprecipitation assay, was found to
      activate ERalpha binding to estrogen-responsive genes in MCF-7 cells. DNA damage
      was measured in cells by comparing ERalpha(+) versus ERalpha(-) cells and 4-OHEN
      versus menadione, a reactive oxygen species (ROS)-generating, but non-estrogenic,
      quinone. 4-OHEN selectively induced DNA damage in ERalpha(+) cells, whereas
      menadione-induced damage was not dependent on cellular ER status. The rate of 4
      OHEN-induced DNA damage was significantly enhanced in ERalpha(+) cells, whereas
      ER status had no effect on the rate of menadione-induced damage. Imaging of ROS
      induced by 4-OHEN showed accumulation selective for the nucleus of ERalpha(+)
      cells within 5 min, whereas in ERalpha(-) or menadione-treated cells, no
      selectivity was observed. These data support ERalpha acting as a Trojan horse
      concentrating 4-OHEN in the nucleus to accelerate the rate of ROS generation and
      thereby amplify DNA damage. The Trojan horse mechanism may be of general
      importance beyond estrogen genotoxins.

PMID- 19158091
TI  - Novel determinants of epithelial sodium channel gating within extracellular thumb
      domains.
AB  - Activity of the epithelial Na(+) channel (ENaC) is modulated by Na(+) self
      inhibition, an allosteric down-regulation of channel open probability by
      extracellular Na(+). We searched for determinants of Na(+) self-inhibition by
      analyzing changes in this inhibitory response resulting from specific mutations
      within the extracellular domains of mouse ENaC subunits. Mutations at
      gammaMet(438) altered the Na(+) self-inhibition response in a substitution
      specific manner. Fourteen substitutions (Ala, Arg, Asp, Cys, Gln, Glu, His, Ile,
      Phe, Pro, Ser, Thr, Tyr, and Val) significantly suppressed Na(+) self-inhibition,
      whereas three mutations (Asn, Gly, and Leu) moderately enhanced the inhibition.
      Met to Lys mutation did not alter Na(+) self-inhibition. Mutations at the
      homologous site in the alpha subunit (G481A, G481C, and G481M) dramatically
      increased the magnitude and speed of Na(+) self-inhibition. Mutations at the
      homologous betaAla(422) resulted in minimal or no change in Na(+) self
      inhibition. Low, high, and intermediate open probabilities were observed in
      oocytes expressing alphaG481Mbetagamma, alphabetagammaM438V, and
      alphaG481M/betagammaM438V, respectively. This pair of residues map to thealpha5
      helix in the extracellular thumb domain in the chicken acid sensing ion channel 1
      structure. Both residues likely reside near the channel surface because both
      alphaG481Cbetagamma and alphabetagammaM438C channels were inhibited by an
      externally applied and membrane-impermeant sulfhydryl reagent. Our results
      demonstrate that alphaGly(481) and gammaMet(438) are functional determinants of
      Na(+) self-inhibition and of ENaC gating and suggest that the thumb domain
      contributes to the channel gating machinery.

PMID- 19158090
TI  - Mi2beta shows chromatin enzyme specificity by erasing a DNase I-hypersensitive
      site established by ACF.
AB  - ATP-dependent chromatin-remodeling enzymes are linked to changes in gene
      expression; however, it is not clear how the multiple remodeling enzymes found in
      eukaryotes differ in function and work together. In this report, we demonstrate
      that the ATP-dependent remodeling enzymes ACF and Mi2beta can direct consecutive,
      opposing chromatin-remodeling events, when recruited to chromatin by different
      transcription factors. In a cell-free system based on the immunoglobulin heavy
      chain gene enhancer, we show that TFE3 induces a DNase I-hypersensitive site in
      an ATP-dependent reaction that requires ACF following transcription factor
      binding to chromatin. In a second step, PU.1 directs Mi2beta to erase an
      established DNase I-hypersensitive site, in an ATP-dependent reaction subsequent
      to PU.1 binding to chromatin, whereas ACF will not support erasure. Erasure
      occurred without displacing the transcription factor that initiated the site.
      Other tested enzymes were unable to erase the DNase I-hypersensitive site.
      Establishing and erasing the DNase I-hypersensitive site required transcriptional
      activation domains from TFE3 and PU.1, respectively. Together, these results
      provide important new mechanistic insight into the combinatorial control of
      chromatin structure.

PMID- 19158092
TI  - Involvement of MicroRNAs in hydrogen peroxide-mediated gene regulation and
      cellular injury response in vascular smooth muscle cells.
AB  - MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs
      that negatively regulate approximately 30% of genes in a cell via degradation or
      translational inhibition of their target mRNAs. However, the effects of reactive
      oxygen species (ROS) on miRNA expression and the roles of miRNAs in ROS-mediated
      gene regulation and biological functions of vascular cells are unclear. Using
      microarray analysis, we demonstrated that miRNAs are aberrantly expressed in
      vascular smooth muscle cells (VSMCs) after treatment with hydrogen peroxide
      (H(2)O(2)). H(2)O(2)-mediated up-regulation of microRNA-21 (miR-21) was further
      confirmed by quantitative real-time PCR. To determine the potential roles of
      miRNAs in H(2)O(2)-mediated gene regulation and cellular effects, miR-21
      expression was down-regulated by miR-21 inhibitor and up-regulated by pre-miR-21.
      H(2)O(2)-induced VSMC apoptosis and death were increased by miR-21 inhibitor and
      decreased by pre-miR-21. Programmed cell death 4(PDCD4) was a direct target of
      miR-21 that was involved in miR-21-mediated effects on VSMCs. Pre-miR-21-mediated
      protective effect on VSMC apoptosis and death was blocked via adenovirus-mediated
      overexpression of PDCD4 without the miR-21 binding site. Moreover, activator
      protein 1 was a downstream signaling molecule of PDCD4 in miR-21-modulated VSMCs.
      The results suggest that miRNAs in VSMCs are sensitive to H(2)O(2) stimulation.
      miRN-21 participates in H(2)O(2)-mediated gene regulation and cellular injury
      response through PDCD4 and the activator protein 1 pathway. miRNAs might play a
      role in vascular diseases related to ROS.

PMID- 19158093
TI  - NBCe1-A Transmembrane Segment 1 Lines the Ion Translocation Pathway.
AB  - The electrogenic Na(+)/HCO(3)(-) cotransporter (NBCe1-A) transports sodium and
      bicarbonate across the basolateral membrane of the renal proximal tubule. In this
      study the structural requirement of transmembrane segment 1 (TM1) residues in
      mediating NBCe1-A transport was investigated. Twenty-five introduced cysteine
      mutants at positions Gln-424 to Gly-448 were tested for their sensitivity to the
      methanethiosulfonate reagents (2-sulfonatoethyl) methanethiosulfonate (MTSES), [2
      (trimethylammonium)ethyl]methanethiosulfonate (MTSET), and (2-aminoethyl)
      methanethiosulfonate (MTSEA). Two mutants, T442C and A435C, showed 100 and 70%
      sensitivity, respectively, to inhibition by all the three methanethiosulfonate
      (MTS) reagents, I441C had >50% sensitivity to MTSET and MTSEA, and A428C had 50%
      sensitivity to MTSEA inhibition. A helical wheel plot showed that mutants T442C,
      A435C, and A428C are clustered on one face of TM1 within a 100 degrees arc.
      Topology analysis of TM1 with biotin maleimide and 2-((5(6)
      tetramethylrhodamine)carboxylamino) ethyl methanethiosulfonate (MTS-TAMRA)
      revealed Thr-442 marks the C-terminal end of TM1 and that extracellular FGGLLG
      stretch is in a small aqueous-accessible cavity. Functional studies indicated
      that Thr-442 resides in a narrow region of the ion translocation pore with strong
      delta(-) helical dipole influence. Analysis of the corresponding residue of NBCe1
      A-Thr-442 in AE1 (Thr-422) shows it is functionally insensitive to MTSES and
      unlabeled with MTS-TAMRA, indicating that AE1-TM1 is oriented differently from
      NBCe1-A. In summary, we have identified residues Thr-442, Ala-435, and Ala-428 in
      TM1 lining the ion translocation pore of NBCe1-A. Our findings are suggestive of
      a delta(-) helical dipole at the C-terminal end of TM1 involving Thr-442 that
      plays a critical role in the function of the cotransporter.

PMID- 19158094
TI  - Use of Fluorescence Resonance Energy Transfer-based Biosensors for the
      Quantitative Analysis of Inositol 1,4,5-Trisphosphate Dynamics in Calcium
      Oscillations.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) is an intracellular messenger that elicits a
      wide range of spatial and temporal Ca(2+) signals, and this signaling versatility
      is exploited to regulate diverse cellular responses. In this study, we have
      developed a series of IP(3) biosensors that exhibit strong pH stability and
      varying affinities for IP(3), as well as a method for the quantitative
      measurement of cytosolic concentrations of IP(3) ([IP(3)](i)) in single living
      cells. We applied this method to elucidate IP(3) dynamics during agonist-induced
      Ca(2+) oscillations, and we demonstrated cell type-dependent differences in IP(3)
      dynamics, a nonfluctuating rise in [IP(3)](i) and repetitive IP(3) spikes during
      Ca(2+) oscillations in COS-7 cells and HSY-EA1 cells, respectively. The size of
      the IP(3) spikes in HSY-EA1 cells varied from 10 to 100 nm, and the [IP(3)](i)
      spike peak was preceded by a Ca(2+) spike peak. These results suggest that
      repetitive IP(3) spikes in HSY-EA1 cells are passive reflections of Ca(2+)
      oscillations, and are unlikely to be essential for driving Ca(2+) oscillations.
      In addition, the interspike periods of Ca(2+) oscillations that occurred during
      the slow rise in [IP(3)](i) were not shortened by the rise in [IP(3)](i),
      indicating that IP(3)-dependent and -independent mechanisms may regulate the
      frequency of Ca(2+) oscillations. The novel method described herein as well as
      the quantitative information obtained by using this method should provide a
      valuable and sound basis for future studies on the spatial and temporal
      regulations of IP(3) and Ca(2+).

PMID- 19158096
TI  - Two sources of mitochondrial NADPH in the yeast Saccharomyces cerevisiae.
AB  - Cells of the yeast Saccharomyces cerevisiae contain three NAD kinases; namely,
      cytosolic Utr1p, cytosolic Yef1p, and mitochondrial Pos5p. Previously, the NADH
      kinase reaction catalyzed by Pos5p, rather than the NAD kinase reaction followed
      by the NADP(+)-dependent dehydrogenase reaction, had been regarded as a critical
      source of mitochondrial NADPH, which plays vital roles in various mitochondrial
      functions. This study demonstrates that the mitochondrial NADH kinase reaction is
      dispensable as a source of mitochondrial NADPH and emphasizes the importance of
      the NAD kinase reaction, followed by the mitochondrial NADP(+)-dependent
      dehydrogenase reaction. Of the potential dehydrogenases (malic enzyme, Mae1p;
      isocitrate dehydrogenase, Idp1p; and acetaldehyde dehydrogenases, Ald4/5p),
      evidence is presented that acetaldehyde dehydrogenases, and in particular Ald4p,
      play a prominent role in generating mitochondrial NADPH in the absence of the
      NADH kinase reaction. The physiological significance of the mitochondrial NADH
      kinase reaction in the absence of Ald4p is also demonstrated. In addition, Pos5p
      is confirmed to have a considerably higher NADH kinase activity than NAD kinase
      activity. Taking these results together, it is proposed that there are two
      sources of mitochondrial NADPH in yeast: one is the mitochondrial Pos5p-NADH
      kinase reaction and the other is the mitochondrial Pos5p-NAD kinase reaction
      followed by the mitochondrial NADP(+)-dependent acetaldehyde dehydrogenase
      reaction.

PMID- 19158095
TI  - Insulin enhances post-translational processing of nascent SREBP-1c by promoting
      its phosphorylation and association with COPII vesicles.
AB  - The regulation of lipid homeostasis by insulin is mediated in part by the
      enhanced transcription of the gene encoding SREBP-1c (sterol regulatory element
      binding protein-1c). Nascent SREBP-1c is synthesized and embedded in the
      endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer
      protein II (COPII) vesicles where two sequential cleavages generate the
      transcriptionally active NH(2)-terminal fragment, nSREBP-1c. There is limited
      indirect evidence to suggest that insulin may also regulate the posttranslational
      processing of the nascent SREBP-1c protein. Therefore, we designed experiments to
      directly assess the action of insulin on the post-translational processing of
      epitope-tagged full-length SREBP-1c and SREBP-2 proteins expressed in cultured
      hepatocytes. We demonstrate that insulin treatment led to enhanced post
      translational processing of SREBP-1c, which was associated with phosphorylation
      of ER-bound nascent SREBP-1c protein that increased affinity of the SREBP-1c
      cleavage-activating protein (SCAP)-SREBP-1c complex for the Sec23/24 proteins of
      the COPII vesicles. Furthermore, chemical and molecular inhibitors of the
      phosphoinositide 3-kinase pathway and its downstream kinase protein kinase B
      (PKB)/Akt prevented both insulin-mediated phosphorylation of nascent SREBP-1c
      protein and its posttranslational processing. Insulin had no effect on the
      proteolysis of nascent SREBP-2 under identical conditions. We also show that in
      vitro incubation of an active PKB/Akt enzyme with recombinant full-length SREBP
      1c led to its phosphorylation. Thus, insulin selectively stimulates the
      processing of SREBP-1c in rat hepatocytes by enhancing the association between
      the SCAP-SREBP-1c complex and COPII proteins and subsequent ER to Golgi transport
      and proteolytic cleavage. This effect of insulin is tightly linked to
      phosphoinositide 3-kinase and PKB/Akt-dependent serine phosphorylation of the
      precursor SREBP-1c protein.

PMID- 19158097
TI  - RNA-protein mutually induced fit: structure of Escherichia coli isopentenyl-tRNA
      transferase in complex with tRNA(Phe).
AB  - tRNAs that read codons starting with U are usually modified at their A37 by
      isopentenyl-tRNA transferases to minimize peptidyl-tRNA slippage in translation.
      The consensus substrate requirements of the isopentenyl-tRNA transferase of
      Escherichia coli, MiaA, have been the focus of extensive study. However, the
      molecular basis of tRNA-MiaA recognition remains unknown. Here we describe the
      2.5A crystal structure of MiaA in complex with substrate tRNA(Phe). Comparative
      structural analysis reveals that the enzymatic reaction involves an RNA-protein
      mutually induced fit mechanism in which large domain movements in MiaA provoke
      the partial unfolding of the substrate tRNA anticodon loop. In addition, we show
      how substrate tRNAs are recognized by MiaA through a combination of direct and
      indirect sequence readouts.

PMID- 19158098
TI  - IGHMBP2 is a ribosome-associated helicase inactive in the neuromuscular disorder
      distal SMA type 1 (DSMA1).
AB  - Distal spinal muscular atrophy type 1 (DSMA1) is an autosomal recessive disease
      that is clinically characterized by distal limb weakness and respiratory
      distress. In this disease, the degeneration of alpha-motoneurons is caused by
      mutations in the immunoglobulin mu-binding protein 2 (IGHMBP2). This protein has
      been implicated in DNA replication, pre-mRNA splicing and transcription, but its
      precise function in all these processes has remained elusive. We have purified
      catalytically active recombinant IGHMBP2, which has enabled us to assess its
      enzymatic properties and to identify its cellular targets. Our data reveal that
      IGHMBP2 is an ATP-dependent 5' --> 3' helicase, which unwinds RNA and DNA
      duplices in vitro. Importantly, this helicase localizes predominantly to the
      cytoplasm of neuronal and non-neuronal cells and associates with ribosomes. DSMA1
      causing amino acid substitutions in IGHMBP2 do not affect ribosome binding yet
      severely impair ATPase and helicase activity. We propose that IGHMBP2 is
      functionally linked to translation, and that mutations in its helicase domain
      interfere with this function in DSMA1 patients.

PMID- 19158099
TI  - Chikungunya and West Nile virus outbreaks: what is happening in north-eastern
      Italy?

PMID- 19158100
TI  - Bacalhao under the Ponte 25 de Abril: impressions from Lisbon.

PMID- 19158101
TI  - Denialism: what is it and how should scientists respond?

PMID- 19158102
TI  - Health and ill health of asylum seekers in Switzerland: an epidemiological study.
AB  - BACKGROUND: Although the focus of health care for people seeking asylum in
      Western European countries is usually on communicable diseases, there is little
      data about the general health care need of this population. In this study, we
      investigated the actual burden of disease among asylum seekers. METHODS: Data
      were collected from a Swiss Health Maintenance Organisation (HMO; a type of
      managed care organization in which physicians act as gate keepers) that was set
      up specifically to provide health care for asylum seekers. The data included
      socio-demographic characteristics, international classification of diseases (ICD
      10) diagnoses and number of clinic visits. Descriptive statistics were used to
      assess the types of health problems and the number of clinic visits. Logistic
      regression analysis was used to determine whether age, gender or country or
      region of origin was predictive in terms of incidence of disease as diagnosed by
      using ICD classifications. RESULTS: The total number of asylum seekers (mean age
      22 years; 38% women) enrolled in the HMO from 2000 through 2003 was 979. Half of
      this group came from the former country of Yugoslavia. The remainder came
      primarily from sub-Saharan Africa, Turkey, Iraq and Sri Lanka. The most common
      health problems encountered in the population included musculoskeletal diseases,
      respiratory diseases, depression and post-traumatic stress disorder. The
      prevalence of all disease clusters was significantly associated with age. One
      fifth of the population did not request health care at all during the time they
      were enrolled in the HMO. It is not known whether those who did not visit the
      medical clinic did not require health care or just chose not to request clinic
      services. CONCLUSIONS: The most frequent health problems encountered in the study
      population were chronic medical conditions, not communicable acute diseases.
      Although health care services provided to asylum seekers usually focus on
      episodic acute care, what this group actually needs is continuity of care.

PMID- 19158103
TI  - Disparities between persons with and without disabilities in their participation
      rates in mass screening.
AB  - OBJECTIVES: The purpose of this study was to determine the number of persons with
      and without disabilities who participated in the National Health Insurance (NHI)
      chronic disease mass screening programs in South Korea. METHODS: The data were
      obtained from mass screening claims submitted to the NHI and National Disability
      Registry. Factors affecting the participation rate included demographic
      variables, socioeconomic status, residential region, and disability type and
      severity. A multiple logistic regression analysis was used to evaluate the
      relationship between participation rates and disability type and severity
      adjusted for confounding factors. RESULTS: The analysis revealed that persons
      with a disability were less likely to participate in mass screening programs than
      those without a disability (35.8% vs. 40.2%). Multiple logistic regression
      analysis indicated that persons with severe disabilities had lower participation
      rates than those without disabilities [adjusted odds ratio (aOR): 0.64, 95%
      confidence interval (CI): 0.63-0.64]. In particular, persons with severe
      disabilities such as limb, brain, visual and internal organ impairment, were less
      likely to participate in the mass screening programs. However, persons with mild
      disability had higher participation rates than those without disabilities (1.03,
      1.02-1.03). CONCLUSIONS: Although the prevalence rates of chronic diseases are
      higher among persons with disabilities, various types of impairments such as
      limb, brain, visual and internal organ impairment, hinder participation in mass
      screening programs for chronic diseases. The reasons for this disparity must be
      investigated and health policies must be altered to make preventative treatments
      more accessible to persons with disabilities.

PMID- 19158105
TI  - Alterations in functional connectivity for language in prematurely born
      adolescents.
AB  - Recent data suggest recovery of language systems but persistent structural
      abnormalities in the prematurely born. We tested the hypothesis that subjects who
      were born prematurely develop alternative networks for processing language.
      Subjects who were born prematurely (n = 22; 600-1250 g birth weight), without
      neonatal brain injury on neonatal cranial ultrasound, and 26 term control
      subjects were examined with a functional magnetic resonance imaging (fMRI)
      semantic association task, the Wechsler Intelligence Scale for Children-III (WISC
      III) and the Clinical Evaluation of Language Fundamentals (CELF). In-magnet task
      accuracy and response times were calculated, and fMRI data were evaluated for the
      effect of group on blood oxygen level dependent (BOLD) activation, the
      correlation between task accuracy and activation and the functional connectivity
      between regions activating to task. Although there were differences in verbal IQ
      and CELF scores between the preterm (PT) and term control groups, there were no
      significant differences for either accuracy or response time for the in-magnet
      task. Both groups activated classic semantic processing areas including the left
      superior and middle temporal gyri and inferior frontal gyrus, and there was no
      significant difference in activation patterns between groups. Clear differences
      between the groups were observed in the correlation between task accuracy and
      activation to task at P < 0.01, corrected for multiple comparisons. Left inferior
      frontal gyrus correlated with accuracy only for term controls and left sensory
      motor areas correlated with accuracy only for PT subjects. Left middle temporal
      gyri correlated with task accuracy for both groups. Connectivity analyses at P <
      0.001 revealed the importance of a circuit between left middle temporal gyri and
      inferior frontal gyrus for both groups. In addition, the PT subjects evidenced
      greater connectivity between traditional language areas and sensory motor areas
      but significantly fewer correlated areas within the frontal lobes when compared
      to term controls. We conclude that at 12 years of age, children born prematurely
      and children born at term had no difference in performance on a simple lexical
      semantic processing task and activated similar areas. Connectivity analyses,
      however, suggested that PT subjects rely upon different neural pathways for
      lexical semantic processing when compared to term controls. Plasticity in network
      connections may provide the substrate for improving language skills in the
      prematurely born.

PMID- 19158106
TI  - Plasma progranulin levels predict progranulin mutation status in frontotemporal
      dementia patients and asymptomatic family members.
AB  - Mutations in the progranulin gene (GRN) are an important cause of frontotemporal
      lobar degeneration (FTLD) with ubiquitin and TAR DNA-binding protein 43 (TDP43)
      positive pathology. The clinical presentation associated with GRN mutations is
      heterogeneous and may include clinical probable Alzheimer's disease. All GRN
      mutations identified thus far cause disease through a uniform disease mechanism,
      i.e. the loss of functional GRN or haploinsufficiency. To determine if expression
      of GRN in plasma could predict GRN mutation status and could be used as a
      biological marker, we optimized a GRN ELISA and studied plasma samples of a
      consecutive clinical FTLD series of 219 patients, 70 control individuals, 72
      early-onset probable Alzheimer's disease patients and nine symptomatic and 18
      asymptomatic relatives of GRN mutation families. All FTLD patients with GRN loss
      of-function mutations showed significantly reduced levels of GRN in plasma to
      about one third of the levels observed in non-GRN carriers and control
      individuals (P < 0.001). No overlap in distributions of GRN levels was observed
      between the eight GRN loss-of-function mutation carriers (range: 53-94 ng/ml) and
      191 non-GRN mutation carriers (range: 115-386 ng/ml). Similar low levels of GRN
      were identified in asymptomatic GRN mutation carriers. Importantly, ELISA
      analyses also identified one probable Alzheimer's disease patient (1.4%) carrying
      a loss-of-function mutation in GRN. Biochemical analyses further showed that the
      GRN ELISA only detects full-length GRN, no intermediate granulin fragments. This
      study demonstrates that using a GRN ELISA in plasma, pathogenic GRN mutations can
      be accurately detected in symptomatic and asymptomatic carriers. The
      approximately 75% reduction in full-length GRN, suggests an unbalanced GRN
      metabolism in loss-of-function mutation carriers whereby more GRN is processed
      into granulins. We propose that plasma GRN levels could be used as a reliable and
      inexpensive tool to identify all GRN mutation carriers in early-onset dementia
      populations and asymptomatic at-risk individuals.

PMID- 19158108
TI  - Comment on: High rate of early virological failure with the once-daily
      tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients.

PMID- 19158107
TI  - Role of right posterior parietal cortex in maintaining attention to spatial
      locations over time.
AB  - Recent models of human posterior parietal cortex (PPC) have variously emphasized
      its role in spatial perception, visuomotor control or directing attention.
      However, neuroimaging and lesion studies also suggest that the right PPC might
      play a special role in maintaining an alert state. Previously, assessments of
      right-hemisphere patients with hemispatial neglect have revealed significant
      overall deficits on vigilance tasks, but to date there has been no demonstration
      of a deterioration of performance over time--a vigilance decrement--considered by
      some to be a key index of a deficit in maintaining attention. Moreover, sustained
      attention deficits in neglect have not specifically been related to PPC lesions,
      and it remains unclear whether they interact with spatial impairments in this
      syndrome. Here we examined the ability of right-hemisphere patients with neglect
      to maintain attention, comparing them to stroke controls and healthy individuals.
      We found evidence of an overall deficit in sustaining attention associated with
      PPC lesions, even for a simple detection task with stimuli presented centrally.
      In a second experiment, we demonstrated a vigilance decrement in neglect patients
      specifically only when they were required to maintain attention to spatial
      locations, but not verbal material. Lesioned voxels in the right PPC spanning a
      region between the intraparietal sulcus and inferior parietal lobe were
      significantly associated with this deficit. Finally, we compared performance on a
      task that required attention to be maintained either to visual patterns or
      spatial locations, matched for task difficulty. Again, we found a vigilance
      decrement but only when attention had to be maintained on spatial information. We
      conclude that sustaining attention to spatial locations is a critical function of
      the human right PPC which needs to be incorporated into models of normal parietal
      function as well as those of the clinical syndrome of hemispatial neglect.

PMID- 19158109
TI  - A review of clinical and microbiological outcomes following treatment of
      infections involving multidrug-resistant Acinetobacter baumannii with
      tigecycline.
AB  - OBJECTIVES: Multidrug-resistant Acinetobacter baumannii (MRAB) is an increasing
      problem in UK hospitals, with many strains now resistant to all available
      antibiotics except polymyxins. Tigecycline has been used for the treatment of
      MRAB as it demonstrates activity in vitro, but there are limited data on its
      clinical efficacy in Gram-negative infections, especially those involving the
      lower respiratory tract or bacteraemia. PATIENTS AND METHODS: A retrospective
      study of the clinical and microbiological outcomes of all patients treated with
      tigecycline for MRAB over an 18 month period was undertaken. RESULTS: Thirty-four
      patients received tigecycline for MRAB or polymicrobial infection involving MRAB.
      Twenty-three (68%) had a positive clinical outcome: microbiological clearance was
      demonstrated in 10 of these. The overall mortality was 41% (n = 14), with nine
      deaths directly attributable to sepsis. Three patients had episodes of Gram
      negative bacteraemia while receiving treatment with tigecycline, with documented
      resistance occurring in one patient. Overall, the correlation between
      microbiological and clinical outcomes was poor. CONCLUSIONS: While tigecycline
      retains excellent in vitro activity against MRAB, its clinical efficacy remains
      uncertain. A prospective study, including the use of tigecycline in combination
      with other antimicrobial agents, should be undertaken to define its role in the
      treatment of MRAB.

PMID- 19158110
TI  - Retrospective evaluation of amphotericin B deoxycholate toxicity in a single
      centre series of haematopoietic stem cell transplantation recipients.

PMID- 19158111
TI  - No evidence for cross-contamination of dried blood spots excised using an office
      hole-punch for HIV-1 drug resistance genotyping.

PMID- 19158112
TI  - The impact of smoking and quitting on household expenditure patterns and medical
      care costs in China.
AB  - BACKGROUND: Smoking remains very common in Chinese men, and the economic burden
      caused by cigarette consumption on smokers and their families may be substantial.
      Using a large nationally representative household survey, the third National
      Health Services Survey (NHSS, 2003), we estimated the economic impact of smoking
      on households. METHODS: Smoking status of all household members (over 15 years)
      was collected by interview for the NHSS, and households classified into one of
      seven categories based on their smoking status. Information on household income
      and expenditure, and use of health services was also obtained. We assessed both
      the "direct" costs (reducing funds available for spending on other commodities
      such as food, education, medical care, etc, using a fractional logit model), and
      "indirect costs" (increasing medical expenditures, using a log-linear model).
      RESULTS: Every five packets of cigarettes consumed per capita per month reduces
      household spending on other commodities, most notably on education (by about 17
      yuan per capita per annum) and medical care (11 yuan). The effects are greatest
      among low-income rural households. Households with quitters spend substantially
      more on medical care than never-smoking households (64 yuan for households with
      two or more quitters). CONCLUSIONS: If a household member smokes, there is less
      money available for commodities such as education and medical care. Medical care
      expenditure is substantially higher among households with quitters, as ill-health
      is the main reason for quitting smoking in China. Smoking impoverishes a
      substantial number of poorer rural households.

PMID- 19158113
TI  - Influence of gender on assessments of disease activity and function in early
      rheumatoid arthritis in relation to radiographic joint damage.
AB  - OBJECTIVE: To evaluate gender differences in score on 28-joint Disease Activity
      Score (DAS28), Health Assessment Questionnaire (HAQ) and Signals Of Functional
      Impairment (SOFI) and to relate these scores to radiographic joint destruction.
      METHODS: In all, 549 patients with early RA (62% women) from the BARFOT (for
      "Better Anti-Rheumatic FarmacOTherapy") study were included. At baseline, 1, 2
      and 5 years DAS28, HAQ and SOFI scoring, and radiographs of hands and feet were
      performed. The radiographs were scored using the van der Heijde-Sharp score.
      RESULTS: In women the DAS28 was significantly higher than in men due to higher
      scores for general health and tender joints. Likewise, HAQ and VAS pain were
      rated significantly higher in women. The SOFI score was worse in men during the
      first 2 years, depending on higher upper limb scores. Total Sharp score
      (TotSharp), erosion score and joint space narrowing score did not differ between
      the sexes at any time point. The DAS28 area under the curve (AUC) correlated
      significantly with TotSharp at 5 years in both genders (r = 0.316, r = 0.313)
      mainly owing to swollen joints and erythrocyte sedimentation rate (ESR). The SOFI
      AUC correlated significantly with TotSharp in women (r = 0.135 to 0.220) but not
      in men. CONCLUSIONS: Despite a similar degree of radiographic joint destruction
      women had, compared with men, worse scores for DAS28 and HAQ, possibly due to
      higher pain perception and less muscular strength and perhaps because men
      overestimate their functional capacity.

PMID- 19158114
TI  - Increased ERK and JNK activities correlate with disease activity in patients with
      systemic lupus erythematosus.
AB  - BACKGROUND: Aberrant signalling along the p21ras/MAP kinase pathway has been
      demonstrated in systemic lupus erythematosus (SLE). OBJECTIVE: To determine
      whether expression and activity of the MAP kinases ERK and JNK reflect disease
      activity in patients with SLE. METHODS: Blood samples of 42 outpatients with SLE
      were prospectively collected during four consecutive visits. The control group
      included 20 healthy subjects. Disease activity was assessed using the SLE Disease
      Activity Index (SLEDAI). Expression of total ERK and JNK kinases and their active
      forms (pERK and pJNK) was determined in whole protein lysates of peripheral blood
      mononuclear cells. RESULTS: The mean levels of the active kinases pERK and pJNK
      were significantly increased in patients with active disease (SLEDAI 4-20) as
      compared with patients with inactive disease (SLEDAI 0-3), p = 0.04, as well as
      with healthy controls, p = 0.03 and p = 0.003 for pERK and pJNK, respectively.
      The percentage of activated forms of ERK and JNK of the total expression of these
      MAP kinases was also gradually increased, reaching 50% for pERK and >40% for pJNK
      in patients with SLE with moderate-to-severe disease (SLEDAI 7-20), p = 0.005, p
      = 0.005 and p = 0.02, p = 0.05 as compared with controls and inactive patients,
      respectively. A decrease of more than three SLEDAI points was associated with a
      significant reduction in the expression of both total and activated forms of ERK
      and JNK, p = 0.03, p = 0.01, respectively. CONCLUSIONS: The results show that ERK
      and JNK activity reflects disease activity in patients with SLE. These MAP
      kinases may serve as additional tools for the evaluation of disease activity and
      management of these patients.

PMID- 19158115
TI  - Cognitive function and 99mTc-ECD brain SPECT are significantly correlated in
      patients with primary Sjogren syndrome: a case-control study.
AB  - OBJECTIVES: To assess subclinical central nervous system (CNS) involvement in
      primary Sjogren syndrome (pSS), by comparing standard brain MRI, in-depth
      neuropsychological testing and (99m)Tc-ECD brain single-photon emission computed
      tomography (SPECT) of patients with pSS with matched controls. METHODS: 10 women
      (<55 years old), with pSS defined using European-American criteria, presence of
      anti-SSA and/or anti-SSB antibodies and no history of neurological involvement
      were prospectively investigated, and compared with 10 age- and sex-matched
      controls. All subjects underwent, within 1 month, brain MRI, neuropsychological
      testing, including overall evaluation and focal cognitive function assessment,
      and (99m)Tc-ECD brain SPECT. RESULTS: (99m)Tc-ECD brain SPECT abnormalities were
      significantly more common in patients with pSS (10/10) than controls (2/10;
      p<0.05). Cognitive dysfunctions, mainly expressed as executive and visuospatial
      disorders, were also significantly more common in patients with pSS (8/10) than
      controls (0/10; p<0.01). Notably, between-group comparisons enabled a significant
      correlation to be established between neuropsychological assessment and (99m)Tc
      ECD brain SPECT abnormalities in patients with pSS (r(s) = 0.49, p<0.01). MRI
      abnormalities in patients and controls did not differ significantly. CONCLUSIONS:
      Neuropsychological testing and (99m)Tc-ECD brain SPECT seem to be the most
      sensitive tools to detect subclinical CNS dysfunction in pSS. The strong
      correlation between cortical hypoperfusion in (99m)Tc-ECD brain SPECT and
      cognitive dysfunction suggests an organic aetiology of CNS dysfunction in pSS.
      These data should be confirmed in a larger study.

PMID- 19158116
TI  - Overlap of coronary disease and pulmonary arterial hypertension in systemic
      sclerosis.
AB  - OBJECTIVES: Pulmonary arterial hypertension (PAH) is a common complication of
      systemic sclerosis (SSc). Symptoms of coronary artery disease (CAD) and PAH are
      closely related and cardiac catheterisation is needed to confirm their diagnosis.
      The aim of the present work was to investigate of the extent of overlap between
      CAD and PAH in patients with SSc. METHODS: Based on non-invasive investigations,
      20 patients out of 120 were suspected to have PAH ("suspected PAH" group).
      Another 10 patients showed signs of coronary disease ("suspected CAD" Group). In
      these 30 patients, right heart catheterisation and coronary angiography were
      performed, and the coronary flow reserve (CFR) was assessed by thermodilution
      technique. RESULTS: In the "suspected PAH" and the "suspected CAD" groups, PAH
      was found in 12/20 and 2/10 cases, and coronary artery stenosis in 9/20 and 6/10
      cases, respectively. Severely reduced CFR was revealed in 7/20 and 3/10 cases,
      respectively. CONCLUSIONS: PAH, CAD and reduced CFR all show a considerable
      overlap in symptomatic patients with SSc. The current non-invasive investigations
      are neither sensitive nor specific enough to make an appropriate distinction
      between these different disease manifestations. A more invasive approach, such as
      coronary angiography at the initial catheterisation, is required to properly
      characterise and treat the different forms of cardiac involvement in SSc.

PMID- 19158117
TI  - Controversial role of plant sterol esters in the management of
      hypercholesterolaemia.

PMID- 19158118
TI  - Late stent malapposition risk is higher after drug-eluting stent compared with
      bare-metal stent implantation and associates with late stent thrombosis.
AB  - AIMS: Late stent malapposition (LSM) may be acquired (LASM) or persistent. LSM
      may play a role in patients who develop late stent thrombosis (ST). Our objective
      was to compare the risk of LASM in bare metal stents (BMS) with drug-eluting
      stents (DES) and to investigate the possible association of both acquired and
      persistent LSM with (very) late ST. METHODS AND RESULTS: We searched PubMed and
      relevant sources from January 2002 to December 2007. Inclusion criteria were: (a)
      intra-vascular ultrasonography (IVUS) at both post-stent implantation and follow
      up; (b) 6-9-month-follow-up IVUS; (c) implantation of either BMS or the following
      DES: sirolimus, paclitaxel, everolimus, or zotarolimus; and (d) follow-up for
      LSM. Of 33 articles retrieved for detailed evaluation, 17 met the inclusion
      criteria. The risk of LASM in patients with DES was four times higher compared
      with BMS (OR = 4.36, CI 95% 1.74-10.94) in randomized clinical trials. The risk
      of (very) late ST in patients with LSM (five studies) was higher compared with
      those without LSM (OR = 6.51, CI 95% 1.34-34.91). CONCLUSION: In our meta
      analysis, the risk of LASM is strongly increased after DES implantation compared
      with BMS. Furthermore, LSM seems to be associated with late and very late ST.

PMID- 19158119
TI  - Bronchial epithelial cells cultured from clinically stable lung allograft
      patients promote the development of macrophages from monocytes rather than
      dendritic cells.
AB  - BACKGROUND: It is understood that chronic allograft failure occurs as a result of
      alloimmune and non-alloimmune injury. Dendritic cells (DC) are thought to be
      crucial in regulating (allo)immune airway damage and interactions with epithelial
      cells are likely. Studies in human lung transplantation are limited, however, and
      the available literature on DC is inconsistent. This study focused on the ex vivo
      influence of primary bronchial epithelial cells derived from lung allografts on
      DC differentiation. METHODS: Epithelial cell conditioned media (ECCM) were added
      to monocytes differentiating into DC under the influence of interleukin-4 and
      granulocyte macrophage-colony stimulating factor. The resultant cells were
      compared with DC cultured without ECCM and with monocyte-derived macrophages.
      Expression of typical DC (eg, CD1a) and macrophage (eg, CD14) markers was
      assessed by flow cytometry. Phenotypical assessments were complemented by
      functional studies of mannose receptor-mediated phagocytosis (FITC-dextran
      uptake) and antigen-presenting capability (mixed lymphocyte reactions). RESULTS:
      Cells exposed to ECCM expressed significantly lower levels of CD1a than unexposed
      DC. CD14 expression and phagocytic function were increased. ECCM cultured cells
      also expressed lower levels of T cell co-stimulatory molecules, secreted an anti
      inflammatory cytokine profile and had significantly reduced antigen-presenting
      capability. CONCLUSION: Using phenotypic and functional approaches, this study
      has shown that ECCM from lung allografts drives the production of macrophage-like
      cells from monocytes rather than DC. The data suggest that epithelial cells may
      restrain airway DC and potential alloimmunity. It is unclear whether the observed
      effect is specifically seen in lung transplant recipients or is a general
      property of bronchial epithelial cells. This may reflect a homeostatic inter
      relationship between airway epithelial and DC populations relevant both to lung
      allografts and the lung more generally.

PMID- 19158120
TI  - An international prospective general population-based study of respiratory work
      disability.
AB  - BACKGROUND: Previous cross-sectional studies have shown that job change due to
      breathing problems at the workplace (respiratory work disability) is common among
      adults of working age. That research indicated that occupational exposure to
      gases, dust and fumes was associated with job change due to breathing problems,
      although causal inferences have been tempered by the cross-sectional nature of
      previously available data. There is a need for general population-based
      prospective studies to assess the incidence of respiratory work disability and to
      delineate better the roles of potential predictors of respiratory work
      disability. METHODS: A prospective general population cohort study was performed
      in 25 centres in 11 European countries and one centre in the USA. A longitudinal
      analysis was undertaken of the European Community Respiratory Health Survey
      including all participants employed at any point since the baseline survey, 6659
      subjects randomly sampled and 779 subjects comprising all subjects reporting
      physician-diagnosed asthma. The main outcome measure was new-onset respiratory
      work disability, defined as a reported job change during follow-up attributed to
      breathing problems. Exposure to dusts (biological or mineral), gases or fumes
      during follow-up was recorded using a job-exposure matrix. Cox proportional
      hazard regression modelling was used to analyse such exposure as a predictor of
      time until job change due to breathing problems. RESULTS: The incidence rate of
      respiratory work disability was 1.2/1000 person-years of observation in the
      random sample (95% CI 1.0 to 1.5) and 5.7/1000 person-years in the asthma cohort
      (95% CI 4.1 to 7.8). In the random population sample, as well as in the asthma
      cohort, high occupational exposure to biological dust, mineral dust or gases or
      fumes predicted increased risk of respiratory work disability. In the random
      sample, sex was not associated with increased risk of work disability while, in
      the asthma cohort, female sex was associated with an increased disability risk
      (hazard ratio 2.8, 95% CI 1.3 to 5.9). CONCLUSIONS: Respiratory work disability
      is common overall. It is associated with workplace exposures that could be
      controlled through preventive measures.

PMID- 19158121
TI  - Ion mobility spectrometry for the detection of volatile organic compounds in
      exhaled breath of patients with lung cancer: results of a pilot study.
AB  - BACKGROUND: Analysis of exhaled breath, especially of volatile organic compounds
      (VOCs), is of increasing interest in the diagnosis of lung cancer. Compared with
      other methods of breath analysis, ion mobility spectrometry (IMS) offers a
      tenfold higher detection rate of VOCs. By coupling the ion mobility spectrometer
      with a multicapillary column as a pre-separation unit, IMS offers the advantage
      of an immediate twofold separation of VOCs with visualisation in a three
      dimensional chromatogram. The total analysis time is about 500 s compared with
      gas chromatography/mass spectrometry (GC/MS) of about 1 h. It therefore seemed
      reasonable to test IMS in breath analysis. METHODS: In a pilot study, 32 patients
      with lung cancer were subjected to a breath analysis by IMS. Their IMS
      chromatograms were compared with those of 54 healthy controls. An IMS that was
      built for special clinical application was used to identify characteristic peaks
      of VOCs which might be relevant for the diagnosis of lung cancer in exhaled air
      of 10 ml volume. RESULTS: By a combination of 23 peak regions within the IMS
      chromatogram, patients with lung cancer, including a patient with carcinoma in
      situ, were classified and differentiated from healthy persons with an error rate
      of zero. CONCLUSION: Breath analysis by IMS can detect a discriminating
      combination of VOCs in patients with lung cancer. By pattern recognition without
      the need for chemical analysis of the underlying VOCs, IMS has the potential to
      facilitate lung cancer diagnosis.

PMID- 19158122
TI  - Low-dose theophylline enhances the anti-inflammatory effects of steroids during
      exacerbations of COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by an
      abnormal inflammatory response mainly to cigarette smoke that flares up during
      exacerbations of the disease (ECOPD). Reduced activity of histone deacetylases
      (HDAC) contributes to enhanced inflammation in stable COPD. It was hypothesised
      that HDAC activity is further reduced during ECOPD and that theophylline, an HDAC
      activator, potentiates the anti-inflammatory effect of steroids in these
      patients. A study was performed to investigate HDAC activity during ECOPD and the
      effects of theophylline on the anti-inflammatory effects of steroids in a
      randomised single-blind controlled study. METHODS: 35 patients hospitalised with
      ECOPD and treated according to international guidelines (including systemic
      steroids) were randomised to receive or not to receive low-dose oral theophylline
      (100 mg twice daily). Before treatment and 3 months after discharge, HDAC and
      nuclear factor-kappaB (NF-kappaB) activity in sputum macrophages, the
      concentration of nitric oxide in exhaled air (eNO) and total antioxidant status
      (TAS), tumour necrosis factor alpha (TNFalpha), interleukin (IL)-6 and IL8 levels
      in sputum supernatants were measured. RESULTS: Patients receiving standard
      therapy showed decreased NF-kappaB activity, eNO concentration and sputum levels
      of TNFalpha, IL6 and IL8, as well as increased TAS during recovery of ECOPD, but
      HDAC activity did not change. The addition of low-dose theophylline increased
      HDAC activity and further reduced IL8 and TNFalpha concentrations. CONCLUSIONS:
      During ECOPD, low-dose theophylline increases HDAC activity and improves the anti
      inflammatory effects of steroids. TRIAL REGISTRATION NUMBER: NCT00671151.

PMID- 19158123
TI  - Oral steroids enhance epithelial repair in nasal polyposis via upregulation of
      the AP-1 gene network.
AB  - BACKGROUND: Chronic mucosal inflammation, epithelial damage and aberrant tissue
      remodelling are common features in nasal polyposis (NP). A study was undertaken
      to characterise the gene expression profile in NP tissues and to explore the
      molecular mechanisms underlying the ameliorative effects of glucocorticosteroids
      (GCs) in NP. METHODS: Two sets of NP biopsies (before and after GC treatment)
      were taken from 10 patients with untreated (GC-naive) bilateral NP. Biopsy
      specimens of inferior turbinate from 6 patients who underwent surgery for nasal
      septal deviation served as nasal mucosal controls. DNA microarrays containing 38
      500 genes were used to characterise the global gene expression profile.
      Functional network analysis was applied to identify the key molecular pathways
      and genes in response to GC treatment (GC-treated). Selected genes were retested
      by quantitative RT-PCR and immunohistochemistry in the same polyps and control
      samples. RESULTS: 64 genes were differentially expressed in GC-treated vs GC
      naive NP tissues. The highest scoring network was assembled around activation
      protein 1 (AP-1), a heterodimer of c-Fos and c-Jun oncoprotein, and five AP-1
      related genes (COX-2, IL-6, AREG, HBEGF and EGR1) with tissue repair function.
      Quantitative PCR confirmed that AP-1 and its related genes were markedly
      repressed in GC-naive polyps and were upregulated after GC treatment.
      Immunohistochemical staining indicated that epithelial restitution in GC-treated
      polyps was associated with increased expression of c-Jun protein. CONCLUSIONS:
      Oral steroids promote epithelial repair in NP via upregulation of the AP-1
      (especially c-Jun) network and its related genes.

PMID- 19158124
TI  - Association of environmental tobacco smoking exposure with an increased risk of
      hospital admissions for pneumonia in children under 5 years of age in Vietnam.
AB  - BACKGROUND: The association between environmental tobacco smoking (ETS) and
      childhood pneumonia has not been established in developed or developing
      countries. A study was conducted to assess the effect and impact of ETS exposure
      on pneumonia among children in central Vietnam. METHODS: A population-based large
      scale cross-sectional survey was conducted covering all residents of 33 communes
      in Khanh Hoa Province, the central part of Vietnam. Information on demographics,
      socioeconomic status and house environment, including smoking status of each
      household member, was collected from householders. Hospital admissions for
      pneumonia among children aged <5 years in each household in the previous 12
      months were recorded based on caregiver's report. RESULTS: A total of 353 525
      individuals living in 75 828 households were identified in the study areas. Of
      these, 24 781 (7.0%) were aged <5 years. The prevalence of ETS was 70.5% and the
      period prevalence of hospital admissions for pneumonia was 2.6%. Multiple
      logistic regression analysis showed that exposure to ETS was independently
      associated with hospital admissions for pneumonia (adjusted odds ratio 1.55, 95%
      CI 1.25 to 1.92). The prevalence of tobacco smoking was higher among men than
      women (51.5% vs 1.5%). It is estimated that 28.7% of childhood pneumonia in this
      community is attributable to ETS. CONCLUSIONS: Children in Vietnam are exposed to
      substantial levels of ETS which results in 44 000 excess hospital admissions due
      to pneumonia each year among children aged <5 years.

PMID- 19158125
TI  - Ultrasound measurement of rectus femoris cross-sectional area and the
      relationship with quadriceps strength in COPD.
AB  - BACKGROUND: Quadriceps weakness and loss of muscle mass predict mortality in
      chronic obstructive pulmonary disease (COPD). It was hypothesised that a reduced
      quadriceps cross-sectional area could be detected by ultrasound in patients with
      COPD compared with healthy subjects, and that measurements relate to strength and
      fat-free mass (FFM). METHODS: Rectus femoris muscle cross-sectional area
      (RF(CSA)) was measured by ultrasound and whole-body FFM estimated using
      electrical bioimpedance. Quadriceps strength was measured by maximum voluntary
      contraction and twitch tension (TwQ) following magnetic femoral nerve
      stimulation. RESULTS: 26 healthy volunteers of mean (SD) age 63 (9) years and 30
      patients with COPD of mean (SD) age 67 (9) years and percentage predicted forced
      expiratory volume in 1 s (FEV(1)) 48.0 (20.8)% with a similar FFM (46.9 (9.3) kg
      vs 46.1 (7.3) kg, p = 0.193) participated in the study. Mean RF(CSA) was reduced
      in patients with COPD by 25% of the mean value in healthy subjects(-115 mm(2);
      95% CI -177 to -54, p = 0.001) and was related to MRC dyspnoea scale score,
      independent of FFM or sex. Maximum voluntary contraction strength was linearly
      related to RF(CSA) in patients with COPD (r = 0.78, p<0.001). TwQ force per unit
      of RF(CSA) was similar in both healthy individuals and those with COPD (mean (SD)
      17 (4) g/mm(2) vs 18 (3) g/mm(2), p = 0.657). Voluntary contraction strength per
      unit of RF(CSA) was dependent on central quadriceps activation and peripheral
      oxygen saturation in COPD. CONCLUSION: Ultrasound measurement of RF(CSA) is an
      effort-independent and radiation-free method of measuring quadriceps muscle cross
      sectional area in patients with COPD that relates to strength.

PMID- 19158126
TI  - Neonatal bronchopulmonary dysplasia predicts abnormal pulmonary HRCT scans in
      long-term survivors of extreme preterm birth.
AB  - BACKGROUND: There is an increasing understanding that extreme preterm birth
      carries a risk of long-term pulmonary sequelae. A study was undertaken to
      investigate if, and in what way, neonatal factors were associated with subsequent
      abnormalities on pulmonary high-resolution CT (HRCT) scanning and if pulmonary
      function was related to these abnormalities. METHODS: HRCT scanning and pulmonary
      function tests were performed less than 2 weeks apart in 74/86 eligible subjects
      (86%) born at a gestational age of < or =28 weeks or with a birth weight of < or
      =1000 g within a defined area in Western Norway in 1982-5 (n = 42) or 1991-2 (n =
      32). Mean age at examination was 18 and 10 years, respectively. HRCT scans were
      interpreted by a paediatric radiologist blinded to the clinical data using a
      structured system allowing scores from 0 to 50. RESULTS: Lung parenchymal
      abnormalities were found in 64 subjects (86%), the median (interquartile range)
      score being 3.0 (1.75-5.0) points. Prolonged neonatal requirement for oxygen
      treatment predicted poor outcome, and an increase of 100 days increased the
      average HRCT score by 3.8 points (p<0.001). There was also a positive association
      of the severity of pulmonary function abnormalities with the extent of HRCT
      abnormalities, exemplified by the relation between forced expiratory volume in 1
      s and total HRCT score (beta = -0.090; p<0.001). CONCLUSIONS: In area-based
      cohorts of long-term survivors of extremely preterm birth, prolonged neonatal
      requirements for oxygen treatment predicted subsequent structural abnormalities
      on HRCT scans and in pulmonary function, and these two outcome measures were
      interrelated.

PMID- 19158127
TI  - Equasy-- an overlooked addiction with implications for the current debate on drug
      harms.

PMID- 19158128
TI  - Cancer risks in chemical production workers exposed to 2-mercaptobenzothiazole.
AB  - OBJECTIVES: To investigate cancer risks in chemical production workers exposed to
      2-mercaptobenzothiazole (MBT). METHODS: The mortality (1955-2005) and cancer
      morbidity experience (1971-2005) of a cohort of 363 male production workers
      exposed to MBT while employed at a chemical factory in north Wales were
      investigated. Two analytical approaches were used, indirect standardisation and
      Poisson regression. RESULTS: Based on national mortality rates, significant
      excess mortality was found for cancers of the large intestine (observed; Obs 8,
      standardised mortality ratio (SMR) 232, 95% CI 100 to 457) and bladder (Obs 8,
      SMR 374, 95% CI 162 to 737). Non-significant excesses were shown for lung cancer
      (Obs 27, SMR 138, 95% CI 91 to 201) and multiple myeloma (Obs 3, SMR 440, 95% CI
      91 to 1287). Based on national cancer incidence rates, significant excess
      morbidity was found for cancer of the bladder (Obs 12, standardised registration
      ratio (SRR) 253, 95% CI 131 to 441) and multiple myeloma (Obs 4, SRR 465, 95% CI
      127 to 1191). Non-significant excesses were shown for cancers of the large
      intestine (Obs 9, SRR 181, 95% CI 83 to 344) and lung (Obs 26, SRR 152, 95% CI 99
      to 223). In analyses that included follow-up information on an additional 1797
      plant employees not exposed to MBT, Poisson regression showed significant
      positive trends both for risks of cancer of the large intestine and for risks of
      multiple myeloma in relation to estimated cumulative exposure to MBT.
      CONCLUSIONS: MBT may be a human carcinogen; confident evaluation awaits findings
      from other studies.

PMID- 19158130
TI  - Predictive validity of health-related fitness in youth: a systematic review.
AB  - The objective of the present systematic review was to investigate whether
      physical fitness in childhood and adolescence is a predictor of cardiovascular
      disease (CVD) risk factors, events and syndromes, quality of life and low back
      pain later in life. Physical fitness-related components were: cardiorespiratory
      fitness, musculoskeletal fitness, motor fitness and body composition. Adiposity
      was considered as both exposure and outcome. The results of 42 studies reporting
      the predictive validity of health-related physical fitness for CVD risk factors,
      events and syndromes as well as the results of five studies reporting the
      predictive validity of physical fitness for low back pain in children and
      adolescents were summarised. Strong evidence was found indicating that higher
      levels of cardiorespiratory fitness in childhood and adolescence are associated
      with a healthier cardiovascular profile later in life. Muscular strength
      improvements from childhood to adolescence are negatively associated with changes
      in overall adiposity. A healthier body composition in childhood and adolescence
      is associated with a healthier cardiovascular profile later in life and with a
      lower risk of death. The evidence was moderate for the association between
      changes in cardiorespiratory fitness and CVD risk factors, and between
      cardiorespiratory fitness and the risk of developing the metabolic syndrome and
      arterial stiffness. Moderate evidence on the lack of a relationship between body
      composition and low back pain was found. Due to a limited number of studies,
      inconclusive evidence emerged for a relationship between muscular strength or
      motor fitness and CVD risk factors, and between flexibility and low back pain.

PMID- 19158129
TI  - Changes in gut hormone levels and negative energy balance during aerobic exercise
      in obese young males.
AB  - We examined whether changes in gut hormone levels due to a single bout of aerobic
      exercise differ between obese young males and normal controls, and attempted to
      determine the involvement of hormonal changes during exercise in the regulation
      of energy balance (EB) in these obese subjects. Seven obese and seven age-matched
      subjects of normal weight participated in exercise and rest sessions. Subjects
      consumed a standardized breakfast that was followed by constant cycling exercise
      at 50% VO(2max) or rest for 60 min. At lunch, a test meal was presented, and
      energy intake (EI) and relative energy intake (REI) were calculated. Blood
      samples were obtained at 30 min intervals during both sessions for measurement of
      glucose, insulin, glucagon, ghrelin, peptide YY (PYY), and glucagon-like peptide
      1 (GLP-1). Plasma levels of PYY and GLP-1 were increased by exercise, whereas
      plasma ghrelin levels were unaffected by exercise. The areas under the curve
      (AUC) of the time courses of PYY and GLP-1 levels did not significantly differ
      between the two groups. In contrast, EI and REI were decreased by exercise in
      both groups, and energy deficit was significantly larger in obese subjects than
      in normal controls. The present findings suggest that short-term EB during a
      single exercise session might be regulated not by increased amounts of these gut
      hormones per se.

PMID- 19158131
TI  - The inguinal release procedure for groin pain: initial experience in 73
      sportsmen/women.
AB  - OBJECTIVE: To assess the impact of the laparoscopic inguinal release procedure
      with mesh reinforcement on athletes with groin pain. DESIGN: Prospective cohort
      study. SETTING: Private sector. PATIENTS: Professional and amateur
      sportsmen/women undergoing the inguinal release for groin pain. MAIN OUTCOME
      MEASUREMENTS: Change in patient's symptoms, functional limitation and time to
      resuming sporting activity following surgery. RESULTS: 73 sportsmen/women
      underwent laparoscopic inguinal release in the study period, 37 (51%) of whom
      were professionals. 95% were male with a median age of 30 years. Following
      operation, patients returned to light training at a median of 1 week, full
      training at 3 weeks (professionals-2 weeks) and playing competitively at 4 weeks
      (professionals-3 weeks). 74% considered themselves match-fit by 4 weeks (84% of
      professionals). Following surgery, there was a highly significant improvement in
      frequency of pain, severity of pain and functional limitation in both the whole
      cohort and professional group. 88% reported a return to full fitness at follow
      up, with 73% reporting complete absence of symptoms. 97% of the cohort thought
      the operation had improved their symptoms. CONCLUSIONS: This study shows that the
      laparoscopic inguinal release procedure may be effective in the treatment of a
      subgroup of athletes with groin pain.

PMID- 19158132
TI  - Multiple risk factors related to familial predisposition to anterior cruciate
      ligament injury: fraternal twin sisters with anterior cruciate ligament ruptures.
AB  - OBJECTIVE: A multifactorial combination of predictors may increase anterior
      cruciate ligament (ACL) injury risk in athletes. The objective of this twin study
      was to examine these risk factors to identify commonalities in risk factors that
      predisposed female fraternal twins to ACL injury. METHODS: Female twins in high
      risk sports were prospectively measured prior to an injury for neuromuscular
      control using three-dimensional motion analysis during landing, hamstrings and
      quadriceps muscular strength on a dynamometer and joint laxity using a modified
      Beighton-Horan index and a Compu-KT arthrometer. Intraoperative measures of
      femoral intercondylar notch width were recorded during ACL reconstruction.
      RESULTS: Abduction angles were increased at one knee in both of the twin sister
      athletes relative to uninjured controls at initial contact and at maximum
      displacement during landing. The twin female athletes that went on to ACL injury
      also demonstrated decreased peak knee flexion motion at both knees than uninjured
      females during landing. The twin athletes also had increased joint laxity and
      decreased hamstrings to quadriceps (H/Q) torque ratios compared to controls.
      Femoral intercondylar notch widths were also below the control mean in the twin
      siblings. CONCLUSIONS: Prescreened mature female twins that subsequently
      experienced ACL injury demonstrated multiple potential risk factors including:
      increased knee abduction angles, decreased knee flexion angles, increased general
      joint laxity, decreased H/Q ratios and femoral intercondylar notch width.

PMID- 19158133
TI  - Markers that predict serious bacterial infection in infants under 3 months of age
      presenting with fever of unknown origin.
AB  - OBJECTIVE: To evaluate potential markers of serious bacterial infection (SBI) in
      infants under 3 months of age presenting with fever of unknown origin. MATERIAL
      AND METHODS: We retrospectively studied all infants under 3 months of age seen in
      the emergency department between January 2004 and December 2006 for a febrile
      syndrome with no identifiable focus. Clinical data, procalcitonin (PCT), C
      reactive protein (CRP) and leucocyte count were evaluated for their ability to
      discriminate between SBI and non-SBI; receiver operating characteristic (ROC)
      curves were constructed for the laboratory markers and analysis was performed by
      multivariate logistic regression. RESULTS: The sample comprised 347 patients
      (23.63% with SBI). Mean PCT, CRP, leucocyte and neutrophil count were
      significantly higher in the group with SBI unlike the other criteria studied. The
      area under the ROC curve (AUC) for PCT was 0.77 (95% CI 0.72 to 0.81) and 0.79
      for CRP (95% CI 0.75 to 0.84); both these variables were stronger predictors than
      leucocyte count (0.67, 95% CI 0.63 to 0.73). In the 15 infants with more invasive
      bacterial infections (sepsis, bacteraemia, bacterial meningitis), the diagnostic
      value of PCT (AUC 0.84, 95% CI 0.79 to 0.88) was higher than CRP (AUC 0.68, 95%
      CI 0.63 to 0.73). In infants who had been febrile for under 12 h, the differences
      between PCT, CRP and leucocyte count were statistically significant in both SBI
      and non-SBI groups, with increasing predictive value of PCT and decreasing value
      of CRP. CONCLUSIONS: PCT, CRP, and leucocyte count have intrinsic predictive
      value for SBI in febrile infants under 3 months of age. The diagnostic value of
      PCT is greater than CRP for more invasive bacterial infections and for fever of
      short duration.

PMID- 19158134
TI  - Demand weaning: infants' answer to professionals' dilemmas.

PMID- 19158135
TI  - Wayward words and watchful waiting: should clinicians be more proactive for the
      preschooler with uncomplicated expressive language delay?

PMID- 19158138
TI  - Out-of-hospital ventricular fibrillation in three adolescents.
AB  - We describe three adolescents who experienced sudden cardiac arrest due to
      ventricular fibrillation in an out-of-hospital setting and survived with good
      neurological outcome despite delayed time to defibrillation. All three were
      treated with prolonged cardiopulmonary resuscitation (CPR) by certified basic
      life support providers prior to first defibrillation. This report stresses the
      importance of early, minimally interrupted, chest compression CPR in children who
      suffer sudden cardiac arrest in the out-of-hospital setting where defibrillation
      could be delayed.

PMID- 19158139
TI  - Towards evidence based medicine for paediatricians. Does oral aciclovir improve
      clinical outcome in immunocompetent children with primary herpes simplex
      gingivostomatitis?

PMID- 19158141
TI  - Towards evidence based medicine for paediatricians. Distinguishing between
      transient synovitis and septic arthritis in the limping child: how useful are
      clinical prediction tools?

PMID- 19158142
TI  - Towards evidence based medicine for paediatricians. Does daily prednisolone
      reduce the risk of relapse secondary to viral infections in steroid-dependent
      nephrotic syndrome?

PMID- 19158143
TI  - Role of post-mortem investigations in determining the cause of sudden unexpected
      death in infancy.

PMID- 19158144
TI  - Isotonic maintenance fluids do not produce hypernatraemia.

PMID- 19158145
TI  - Bile-stained vomiting in neonates.

PMID- 19158146
TI  - Case reports of factitious illness are unlikely to be published in the UK.

PMID- 19158148
TI  - Toxic additives in medication for preterm infants.
AB  - BACKGROUND: Little is known about exposure of preterm infants to excipients
      during routine clinical care. OBJECTIVE: To document excipient exposure in
      vulnerable preterm babies in a single centre, taking into account chronic lung
      disease (CLD) as a marker of illness severity. DESIGN: Excipient exposure after
      treatment with eight oral liquid medications was determined by retrospectively
      analysing the drug charts of infants admitted to a neonatal unit. SETTING: The
      Leicester Neonatal Service. PARTICIPANTS: 38 infants born between June 2005 and
      July 2006 who were less than 30 weeks' gestation and 1500 g in weight at birth
      and managed in Leicester to discharge. RESULTS: The 38 infants represented 53% of
      the eligible target group; 7/38 infants had CLD. During their in-patient stay,
      infants were exposed to over 20 excipients including ethanol and propylene
      glycol, chemicals associated with neurotoxicity. Infants with CLD were exposed to
      higher concentrations of these toxins. Infants were also exposed to high
      concentrations of sorbitol, with some infants being exposed to concentrations in
      excess of recommended guidelines for maximum exposure in adults. CONCLUSIONS:
      Preterm infants are commonly exposed to excipients, some of which are potentially
      toxic. Strategies aimed at reducing excipient load in preterm infants are
      urgently required.

PMID- 19158149
TI  - Online survey of current autopsy practice.
AB  - AIMS: The Royal College of Pathologists (RCPath) has for several years published
      guidance on good autopsy practice. However, pressures such as time, cost and the
      introduction of the Human Tissue Act have generated suggestions that there is a
      discrepancy between the published guidelines and what can realistically be
      achieved in daily practice. The aims of this study were to determine the extent
      to which practising pathologists agree with this complaint, and what suggestions
      they might have for its resolution. METHODS: All histopathologists in the UK on
      the RCPath database (n = 1213) were sent an email invitation to participate in an
      online questionnaire. RESULTS: 406 pathologists completed the survey, providing
      numerical data and free-text responses. Results concerning pressures of time,
      resources and limitations on examination and sampling were in keeping with those
      expected from recent issues raised. The view that RCPath guidelines are higher
      than can be achieved in routine coronial autopsy practice was widely supported,
      but only 45% stated that the RCPath should publish separate guidelines to
      differentiate between hospital ("consent") autopsies and medico-legal cases.
      CONCLUSION: The circumstances under which coronial autopsies are conducted in
      many parts of the UK make it difficult or impossible to comply with current
      RCPath guidance. Pathologists disagree on whether this situation demands a
      reduction of RCPath standards, an improvement in autopsy practice in medico-legal
      cases to current RCPath standards, or the implementation of "double standards".
      Resolution of this dilemma requires clarification of exactly what a coronial
      autopsy is trying to achieve.

PMID- 19158150
TI  - Application of cumulative odds logistic model on risk factors analysis for
      sexually transmitted infections among female sex workers in Kaiyuan city, Yunnan
      province, China.
AB  - OBJECTIVES: To investigate the epidemiology of sexually transmitted infections
      (STI) among female sex workers (FSW) in Kaiyuan city, Yunnan province, China, and
      to identify risk factors associated with STI. METHODS: A cross-sectional study of
      737 FSW was carried out from March to May 2006, with confidential interviews and
      laboratory tests for STI. A cumulative logit model was used to evaluate the risk
      factors for STI. RESULTS: The overall prevalence of HIV is 10.3%. The prevalence
      of syphilis, herpes simplex virus type 2, gonorrhoea, chlamydia and trichomonas
      was 7.5%, 68.1%, 8.3%, 25.9% and 10.6%, respectively. In multivariate cumulative
      odds logistic analysis, the factors associated with STI were education level,
      living in the entertainment location, injection drug use, non-injection drug use,
      over five clients in the previous week and inconsistent use of condoms with
      clients. CONCLUSION: The findings highlight the gravity of the STI epidemic among
      FSW in China, where sexual transmission has now overtaken unsafe injection
      practices as the dominant mode of HIV transmission. Targeted intervention
      programmes for FSW should focus on increasing condom use, strengthening knowledge
      and awareness of STI/HIV and encouraging routine screening and treatment-seeking
      behaviours. Reducing the spread of STI also has profound implications for the
      prevention of HIV.

PMID- 19158151
TI  - Dietary grape seed proanthocyanidins inhibit 12-O-tetradecanoyl phorbol-13
      acetate-caused skin tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated
      mouse skin, which is associated with the inhibition of inflammatory responses.
AB  - Grape seed proanthocyanidins (GSPs) possess anticarcinogenic activities. Here, we
      assessed the effects of dietary GSPs on 12-O-tetradecanoylphorbol-13-acetate
      (TPA)-induced skin tumor promotion in 7,12-dimethylbenz[a]anthracene (DMBA)
      initiated mouse skin. Administration of dietary GSPs (0.2 and 0.5%, wt/wt)
      supplemented with control AIN76A diet resulted in significant inhibition of TPA
      induced skin tumor promotion in C3H/HeN mice. The mice treated with GSPs
      developed a significantly lower tumor burden in terms of the percentage of mice
      with tumors (P < 0.05), total number of tumors per group (P < 0.01, n = 20) and
      total tumor volume per tumor-bearing mouse (P < 0.01-0.001) as compared with the
      mice that received the control diet. GSPs also delayed the malignant progression
      of papillomas into carcinomas. As TPA-induced inflammatory responses are used
      routinely as markers of skin tumor promotion, we assessed the effect of GSPs on
      biomarkers of TPA-induced inflammation. Immunohistochemical analysis and western
      blotting revealed that GSPs significantly inhibited expression of cyclooxygenase
      2 (COX-2), prostaglandin E(2) (PGE(2)) and markers of proliferation
      (proliferating cell nuclear antigen and cyclin D1) in both the DMBA-initiated/TPA
      promoted mouse skin and skin tumors. In short-term experiments in which the mouse
      skin was treated with acute or multiple TPA applications, we found that dietary
      GSPs inhibited TPA-induced edema, hyperplasia, leukocytes infiltration,
      myeloperoxidase, COX-2 expression and PGE(2) production in the mouse skin. The
      inhibitory effect of GSPs was also observed against other structurally different
      skin tumor promoter-induced inflammation in the skin. Together, our results show
      that dietary GSPs inhibit chemical carcinogenesis in mouse skin and that the
      inhibition of skin tumorigenesis by GSPs is associated with the inhibition of
      inflammatory responses caused by tumor promoters.

PMID- 19158152
TI  - Levosimendan vs. dobutamine: outcomes for acute heart failure patients on beta
      blockers in SURVIVE.
AB  - AIMS: Many chronic heart failure (CHF) patients take beta-blockers. When such
      patients are hospitalized for decompensation, it remains unclear how ongoing beta
      blocker treatment will affect outcomes of acute inotrope therapy. We aimed to
      assess outcomes of SURVIVE patients who were on beta-blocker therapy before
      receiving a single intravenous infusion of levosimendan or dobutamine. METHODS
      AND RESULTS: Cox proportional hazard regression revealed all-cause mortality
      benefits of levosimendan treatment over dobutamine when the SURVIVE population
      was stratified according to baseline presence/absence of CHF history and use/non
      use of beta-blocker treatment at baseline. All-cause mortality was lower in the
      CHF/levosimendan group than in the CHF/dobutamine group, showing treatment
      differences by hazard ratio (HR) at days 5 (3.4 vs. 5.8%; HR, 0.58, CI 0.33-1.01,
      P = 0.05) and 14 (7.0 vs. 10.3%; HR, 0.67, CI 0.45-0.99, P = 0.045). For patients
      who used beta-blockers (n = 669), mortality was significantly lower for
      levosimendan than dobutamine at day 5 (1.5 vs. 5.1% deaths; HR, 0.29; CI 0.11
      0.78, P = 0.01). CONCLUSION: Levosimendan may be better than dobutamine for
      treating patients with a history of CHF or those on beta-blocker therapy when
      they are hospitalized with acute decompensations. These findings are preliminary
      but important for planning future studies.

PMID- 19158153
TI  - Influence of gender of physicians and patients on guideline-recommended treatment
      of chronic heart failure in a cross-sectional study.
AB  - AIMS: Clinical outcomes of patients with chronic heart failure (CHF) have
      improved, but evidence-based treatment appears to be imbalanced depending on
      patients' and physicians' gender. We aimed to determine the interactions of
      gender with medical treatment of CHF. METHODS AND RESULTS: Consecutive patients
      with CHF (n = 1857) were evaluated regarding co-morbidities, New York Heart
      Association classification, current medical treatment, and dosage of angiotensin
      converting enzyme-inhibitors (ACE-Is) and beta-blockers. Gender of patients and
      treating physicians was recorded. Baseline characteristics of patients and
      physicians were comparable for males and females. Female patients were less
      frequently treated with ACE-Is, angiotensin-receptor blockers, or beta-blockers.
      Achieved doses were lower in female compared with male patients. Guideline
      recommended drug use and achieved target doses tended to be higher in patients
      treated by female physicians. There was no different treatment for male or female
      patients by female physicians, whereas male physicians used significantly less
      medication and lower doses in female patients. In multivariable analysis, female
      gender of physicians was an independent predictor of use of beta-blockers.
      CONCLUSION: Treatment of CHF is influenced by patients', but also physicians'
      gender with regard to evidenced-based drugs and their dosage. Physicians should
      be aware of this problem in order to avoid gender-related treatment imbalances.

PMID- 19158154
TI  - Immunosuppressive human anti-lymphocyte autoantibodies specific for the type 1
      sphingosine 1-phosphate receptor.
AB  - Anti-lymphocyte antibodies (Abs) that suppress T-cell chemotactic and other
      responses to sphingosine 1-phosphate (S1P), but not to chemokines, were found in
      a lymphopenic patient with recurrent infections. Lymphocyte type 1 S1P receptor
      (S1P(1)) that transduces S1P chemotactic stimulation was recognized by patient
      Abs in Western blots of T cells, S1P(1) transfectants, and S1P(1)-hemagglutinin
      purified by monoclonal anti-hemagglutinin Ab absorption. The amino terminus of
      S1P(1), but not any extracellular loop, prevented anti-S1P(1) Ab suppression of
      S1P(1) signaling and T-cell chemotaxis to S1P. Human purified anti-S1P(1) Abs
      decreased mouse blood lymphocyte levels by a mean of 72%, suppressed mouse T-cell
      chemotaxis to S1P in vivo, and significantly reduced the severity of dextran
      sodium sulfate-induced colitis in mice. Human Abs to the amino terminus of S1P(1)
      suppress T-cell trafficking sufficiently to impair host defense and provide
      therapeutic immunosuppression.

PMID- 19158155
TI  - Diet-induced obesity in female mice leads to peroxidized lipid accumulations and
      impairment of hippocampal neurogenesis during the early life of their offspring.
AB  - Maternal obesity may affect the child's long-term development and health.
      However, there is little information about the involvement of maternal obesity in
      the brain development of offspring. Here, we investigated the effects of maternal
      obesity on the hippocampal formation of offspring. Adult female mice were fed
      either a normal diet (ND, 4% fat) or a high-fat diet (HFD, 32% fat) 6 wk before
      mating and throughout pregnancy and the majority of lactation. We found that
      infants from HFD-fed dams (HFD offspring) showed obesity and hyperlipidemia
      during suckling. In HFD offspring, lipid peroxidation was promoted in serum and
      the hippocampal dentate gyrus, where neurogenesis takes place throughout
      postnatal life. Using a BrdU-pulse labeling study, we showed that
      malondialdehyde, a product of peroxidized lipids, reduced the proliferation of
      hippocampal progenitor cells in vitro and that neurogenesis in HFD offspring
      during postnatal development was similarly lowered relative to the ND animals.
      These results indicated that maternal obesity impairs hippocampal progenitor cell
      division and neuronal production in young offspring possibly due to metabolic and
      oxidative changes.

PMID- 19158157
TI  - When I use a word ... words misheard: medical mondegreens.

PMID- 19158159
TI  - Gclust: trans-kingdom classification of proteins using automatic individual
      threshold setting.
AB  - MOTIVATION: Trans-kingdom protein clustering remained difficult because of large
      sequence divergence between eukaryotes and prokaryotes and the presence of a
      transit sequence in organellar proteins. A large-scale protein clustering
      including such divergent organisms needs a heuristic to efficiently select
      similar proteins by setting a proper threshold for homologs of each protein. Here
      a method is described using two similarity measures and organism count. RESULTS:
      The Gclust software constructs minimal homolog groups using all-against-all
      BLASTP results by single-linkage clustering. Major points include (i) estimation
      of domain structure of proteins; (ii) exclusion of multi-domain proteins; (iii)
      explicit consideration of transit peptides; and (iv) heuristic estimation of a
      similarity threshold for homologs of each protein by entropy-optimized organism
      count method. The resultant clusters were evaluated in the light of power law.
      The software was used to construct protein clusters for up to 95 organisms.
      AVAILABILITY: Software and data are available at http://gclust.c.u
      tokyo.ac.jp/Gclust_Download.html.

PMID- 19158160
TI  - DSSTox chemical-index files for exposure-related experiments in ArrayExpress and
      Gene Expression Omnibus: enabling toxico-chemogenomics data linkages.
AB  - SUMMARY: The Distributed Structure-Searchable Toxicity (DSSTox) ARYEXP and GEOGSE
      files are newly published, structure-annotated files of the chemical-associated
      and chemical exposure-related summary experimental content contained in the
      ArrayExpress Repository and Gene Expression Omnibus (GEO) Series (based on data
      extracted on September 20, 2008). ARYEXP and GEOGSE contain 887 and 1064 unique
      chemical substances mapped to 1835 and 2381 chemical exposure-related experiment
      accession IDs, respectively. The standardized files allow one to assess, compare
      and search the chemical content in each resource, in the context of the larger
      DSSTox toxicology data network, as well as across large public cheminformatics
      resources such as PubChem (http://pubchem.ncbi.nlm.nih.gov). AVAILABILITY: Data
      files and documentation may be accessed online at http://epa.gov/ncct/dsstox/.

PMID- 19158156
TI  - CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis.
AB  - Lymphocytes help determine whether gut epithelial cells proliferate or
      differentiate but are not known to affect whether they live or die. Here, we
      report that lymphocytes play a controlling role in mediating gut epithelial
      apoptosis in sepsis but not under basal conditions. Gut epithelial apoptosis is
      similar in unmanipulated Rag-1(-/-) and wild-type (WT) mice. However, Rag-1(-/-)
      animals have a 5-fold augmentation in gut epithelial apoptosis following cecal
      ligation and puncture (CLP) compared to septic WT mice. Reconstitution of
      lymphocytes in Rag-1(-/-) mice via adoptive transfer decreases intestinal
      apoptosis to levels seen in WT animals. Subset analysis indicates that CD4(+) but
      not CD8(+), gammadelta, or B cells are responsible for the antiapoptotic effect
      of lymphocytes on the gut epithelium. Gut-specific overexpression of Bcl-2 in
      transgenic mice decreases mortality following CLP. This survival benefit is
      lymphocyte dependent since gut-specific overexpression of Bcl-2 fails to alter
      survival when the transgene is overexpressed in Rag-1(-/-) mice. Further,
      adoptively transferring lymphocytes to Rag-1(-/-) mice that simultaneously
      overexpress gut-specific Bcl-2 results in improved mortality following sepsis.
      Thus, sepsis unmasks CD4(+) lymphocyte control of gut apoptosis that is not
      present under homeostatic conditions, which acts as a key determinant of both
      cellular survival and host mortality.

PMID- 19158161
TI  - Detecting gene clusters under evolutionary constraint in a large number of
      genomes.
AB  - MOTIVATION: Spatial clusters of genes conserved across multiple genomes provide
      important clues to gene functions and evolution of genome organization. Existing
      methods of identifying these clusters often made restrictive assumptions, such as
      exact conservation of gene order, and relied on heuristic algorithms. RESULTS: We
      developed a very efficient algorithm based on a 'gene teams' model that allows
      genes in the clusters to appear in different orders. This allows us to detect
      conserved gene clusters under flexible evolutionary constraints in a large number
      of genomes. Our statistical evaluation incorporates the evolutionary relationship
      among genomes, a key aspect that has been missing in most previous studies. We
      conducted a large-scale analysis of 133 bacterial genomes. Our results confirm
      that our approach is an effective way of uncovering functionally related genes.
      The comparison with known operons and the analysis of the structural properties
      of our predicted clusters suggest that operons are an important source of
      constraint, but there are also other forces that determine evolution of gene
      order and arrangement. Using our method, we predicted functions of many poorly
      characterized genes in bacterial. The combined algorithmic and statistical
      methods we present here provide a rigorous framework for systematically studying
      evolutionary constraints of genomic contexts. AVAILABILITY: The software, data
      and the full results of this article are available online at
      http://www.ews.uiuc.edu/~xuling/mcmusec.

PMID- 19158162
TI  - Disperse--a software system for design of selector probes for exon resequencing
      applications.
AB  - SUMMARY: Selector probes enable the amplification of many selected regions of the
      genome in multiplex. Disperse is a software pipeline that automates the procedure
      of designing selector probes for exon resequencing applications. AVAILABILITY:
      Software and documentation is available at http://bioinformatics.org/disperse

PMID- 19158163
TI  - Patterns and predictors of CD4 T-cell counts among children born to HIV-infected
      women in Tanzania.
AB  - We assessed age-specific CD4 T-cell counts and their determinants among Tanzanian
      children born to HIV-infected mothers to address a major research gap. A total of
      474 HIV-uninfected and 69 HIV-infected children were followed until age of 12
      months. Maternal predictors were measured during pregnancy and child predictors
      at birth and throughout the follow up. Child CD4 T-cell counts were evaluated at
      the age of 3 months and subsequent 3-month intervals; they decreased linearly
      among HIV-infected (beta = -8 cells per week; 95% CI -12 to -4; P = 0.0003) and
      increased linearly among HIV-uninfected children (beta = 4 cells/week; 95% CI 2
      7; P = 0.0008). Decreased child counts were predicted by low child anthropometry,
      maternal HIV stage > or =2, and maternal mid-upper arm circumference <27 cm among
      HIV-infected children; and by weight-for-height <-2 z-score, maternal HIV stage >
      or =2, maternal erythrocyte sedimentation rate <81 mm/h and maternal haemoglobin
      <8.5 g/dl among HIV-uninfected children. The maternal and child predictors
      described may serve as intervention targets among HIV-exposed children.

PMID- 19158164
TI  - Acquired methemoglobinemia due to contaminated colours: a preventable disaster.

PMID- 19158165
TI  - Why universal BCG in UK was deemed not necessary.

PMID- 19158166
TI  - Poster boarding.

PMID- 19158168
TI  - Statins and familial hypercholesterolaemia.

PMID- 19158169
TI  - Quality and outcomes framework. QOF as Trojan horse.

PMID- 19158170
TI  - Infectious diseases in people with intellectual disabilities.

PMID- 19158171
TI  - Coffee creamer as infant food. Nestle's works to ensure appropriate use of milk
      products.

PMID- 19158173
TI  - Surgical safety checklists.

PMID- 19158175
TI  - UK government sets up inquiry into premature deaths in people with learning
      disabilities.

PMID- 19158178
TI  - United Health Group settles with US securities watchdog.

PMID- 19158179
TI  - Sudden onset of pain in the eye and blurring of vision.

PMID- 19158182
TI  - A 3(1/2) year old girl presenting with strabismus.

PMID- 19158183
TI  - FGF ligands in Drosophila have distinct activities required to support cell
      migration and differentiation.
AB  - Fibroblast growth factor (FGF) signaling controls a vast array of biological
      processes including cell differentiation and migration, wound healing and
      malignancy. In vertebrates, FGF signaling is complex, with over 100 predicted FGF
      ligand-receptor combinations. Drosophila melanogaster presents a simpler model
      system in which to study FGF signaling, with only three ligands and two FGF
      receptors (FGFRs) identified. Here we analyze the specificity of FGFR [Heartless
      (Htl) and Breathless (Btl)] activation by each of the FGF ligands [Pyramus (Pyr),
      Thisbe (Ths) and Branchless (Bnl)] in Drosophila. We confirm that both Pyr and
      Ths can activate Htl, and that only Bnl can activate Btl. To examine the role of
      each ligand in supporting activation of the Htl FGFR, we utilize genetic
      approaches that focus on the earliest stages of embryonic development. When pyr
      and ths are equivalently expressed using the Gal4 system, these ligands support
      qualitatively different FGFR signaling responses. Both Pyr and Ths function in a
      non-autonomous fashion to support mesoderm spreading during gastrulation, but Pyr
      exhibits a longer functional range. pyr and ths single mutants exhibit defects in
      mesoderm spreading during gastrulation, yet only pyr mutants exhibit severe
      defects in dorsal mesoderm specification. We demonstrate that the Drosophila FGFs
      have different activities and that cell migration and differentiation have
      different ligand requirements. Furthermore, these FGF ligands are not regulated
      solely by differential expression, but the sequences of these linked genes have
      evolved to serve different functions. We contend that inherent properties of FGF
      ligands make them suitable to support specific FGF-dependent processes, and that
      FGF ligands are not always interchangeable.

PMID- 19158184
TI  - The interaction of xKaiso with xTcf3: a revised model for integration of
      epigenetic and Wnt signalling pathways.
AB  - We demonstrate that a direct interaction between the methyl-CpG-dependent
      transcription repressor Kaiso and xTcf3, a transducer of the Wnt signalling
      pathway, results in their mutual disengagement from their respective DNA-binding
      sites. Thus, the transcription functions of xTcf3 can be inhibited by
      overexpression of Kaiso in cell lines and Xenopus embryos. The interaction of
      Kaiso with xTcf3 is highly conserved and is dependent on its zinc-finger domains
      (ZF1-3) and the corresponding HMG DNA-binding domain of TCF3/4 factors. Our data
      rule out a model suggesting that xKaiso is a direct repressor of Wnt signalling
      target genes in early Xenopus development via binding to promoter-proximal CTGCNA
      sequences as part of a xTcf3 repressor complex. Instead, we propose that mutual
      inhibition by Kaiso/TCF3 of their DNA-binding functions may be important in
      developmental or cancer contexts and acts as a regulatory node that integrates
      epigenetic and Wnt signalling pathways.

PMID- 19158185
TI  - The non-methylated DNA-binding function of Kaiso is not required in early Xenopus
      laevis development.
AB  - Mammalian forms of the transcription repressor, Kaiso, can reportedly bind
      methylated DNA and non-methylated CTGCNA motifs. Here we compare the DNA-binding
      properties of Kaiso from frog, fish and chicken and demonstrate that only the
      methyl-CpG-binding function of Kaiso is evolutionarily conserved. We present
      several independent experimental lines of evidence that the phenotypic
      abnormalities associated with xKaiso-depleted Xenopus laevis embryos are
      independent of the putative CTGCNA-dependent DNA-binding function of xKaiso. Our
      analysis suggests that xKaiso does not play a role in the regulation of either
      xWnt11 or Siamois, key signalling molecules in the Wnt pathway during X. laevis
      gastrulation. The major phenotypic defects associated with xKaiso depletion are
      premature transcription activation before the mid-blastula transition and
      concomitant activation of a p53-dependent cell-death pathway.

PMID- 19158186
TI  - Identification of direct T-box target genes in the developing zebrafish mesoderm.
AB  - The zebrafish genes spadetail (spt) and no tail (ntl) encode T-box transcription
      factors that are important for early mesoderm development. Although much has been
      done to characterize these genes, the identity and location of target regulatory
      elements remain largely unknown. Here, we survey the genome for downstream target
      genes of the Spt and Ntl T-box transcription factors. We find evidence for
      extensive additive interactions towards gene activation and limited evidence for
      combinatorial and antagonistic interactions between the two factors. Using in
      vitro binding selection assays to define Spt- and Ntl-binding motifs, we searched
      for target regulatory sequence via a combination of binding motif searches and
      comparative genomics. We identified regulatory elements for tbx6 and deltaD, and,
      using chromatin immunoprecipitation, in vitro DNA binding assays and transgenic
      methods, we provide evidence that both are directly regulated by T-box
      transcription factors. We also find that deltaD is directly activated by T-box
      factors in the tail bud, where it has been implicated in starting the
      segmentation clock, suggesting that spt and ntl act upstream of this process.

PMID- 19158187
TI  - Finding 3D motifs in ribosomal RNA structures.
AB  - The identification of small structural motifs and their organization into larger
      subassemblies is of fundamental interest in the analysis, prediction and design
      of 3D structures of large RNAs. This problem has been studied only sparsely, as
      most of the existing work is limited to the characterization and discovery of
      motifs in RNA secondary structures. We present a novel geometric method for the
      characterization and identification of structural motifs in 3D rRNA molecules.
      This method enables the efficient recognition of known 3D motifs, such as
      tetraloops, E-loops, kink-turns and others. Furthermore, it provides a new way of
      characterizing complex 3D motifs, notably junctions, that have been defined and
      identified in the secondary structure but have not been analyzed and classified
      in three dimensions. We demonstrate the relevance and utility of our approach by
      applying it to the Haloarcula marismortui large ribosomal unit. Pending the
      implementation of a dedicated web server, the code accompanying this article,
      written in JAVA, is available upon request from the contact author.

PMID- 19158188
TI  - DNA modification of live cell surface.
AB  - We report a novel approach for the attachment of DNA fragments to the surface of
      live cells. By using fluorescence microscopy and flow cytometry we demonstrated
      that our synthetic conjugates of fatty acid with oligonucleotides can be
      incorporated in plasma membrane and then hybridized with complementary sequences
      at the cell surface. Method permits to control amount of immobilized DNA on the
      cell surface. All procedures can be completed within minutes and do not alter
      cell viability. Using this approach we tethered floating myeloid HL-60 cells to
      adherent A431 epitheliocytes in a sequence specific fashion. Thus, this method
      allows rapid and simple DNA multicoding of the cell surface and, therefore, opens
      new opportunities in manipulating with cell-cell interactions.

PMID- 19158190
TI  - CRIM1 is localized to the podocyte filtration slit diaphragm of the adult human
      kidney.
AB  - BACKGROUND: CRIM1 is a plasma membrane bound protein containing six cysteine-rich
      repeats (CRR). Through these, CRIM1 has been shown to interact with a subgroup of
      the TGF-beta superfamily, the bone morphogenic proteins (BMP) isoforms 2, 4 and
      7. The probable action is to modulate the signalling properties of these factors.
      CRIM1 has also been shown to regulate the release of VEGFA by podocytes during
      renal organogenesis. Knock-out studies in mice have shown that CRIM1 is
      critically involved in the development of the central nervous system, eye and
      kidney. Replacement of CRIM1 with a defective version leads to renal dysgenesis
      and perinatal death. We have analysed the distribution of CRIM1 in adult human
      renal tissue. METHODS: To this end, we have used immunofluorescence,
      immunohistochemistry and immunoelectron microscopy. We performed western blotting
      for the CRIM1 protein, using lysates from isolated glomerular podocytes and human
      renal tissue homogenate. By using quantitative PCR, we compared the CRIM1 mRNA
      levels in podocytes, human renal tissue homogenate, primary human renal proximal
      tubular epithelial cells and primary human pulmonary artery smooth muscle cells.
      RESULTS: The results show that in the human adult kidney, CRIM1 is mainly
      expressed in the glomerular podocytes and is associated with the insertional
      region of the filtration slit diaphragm (SD) of the podocyte pedicles.
      CONCLUSIONS: CRIM1 is a protein that should be added to the list of proteins
      associated with the podocyte filtration SD and with the probable action of
      modulating BMP and VEGFA signalling.

PMID- 19158189
TI  - Fidelity of plus-strand priming requires the nucleic acid chaperone activity of
      HIV-1 nucleocapsid protein.
AB  - During minus-strand DNA synthesis, RNase H degrades viral RNA sequences,
      generating potential plus-strand DNA primers. However, selection of the 3'
      polypurine tract (PPT) as the exclusive primer is required for formation of viral
      DNA with the correct 5'-end and for subsequent integration. Here we show a new
      function for the nucleic acid chaperone activity of HIV-1 nucleocapsid protein
      (NC) in reverse transcription: blocking mispriming by non-PPT RNAs. Three
      representative 20-nt RNAs from the PPT region were tested for primer extension.
      Each primer had activity in the absence of NC, but less than the PPT. NC reduced
      priming by these RNAs to essentially base-line level, whereas PPT priming was
      unaffected. RNase H cleavage and zinc coordination by NC were required for
      maximal inhibition of mispriming. Biophysical properties, including thermal
      stability, helical structure and reverse transcriptase (RT) binding affinity,
      showed significant differences between PPT and non-PPT duplexes and the trends
      were generally correlated with the biochemical data. Binding studies in reactions
      with both NC and RT ruled out a competition binding model to explain NC's
      observed effects on mispriming efficiency. Taken together, these results
      demonstrate that NC chaperone activity has a major role in ensuring the fidelity
      of plus-strand priming.

PMID- 19158191
TI  - Differential effects of chlorthalidone versus spironolactone on muscle
      sympathetic nerve activity in hypertensive patients.
AB  - CONTEXT: Previous studies in rats indicated that thiazide-type diuretics reduced
      blood pressure (BP) and triggered baroreflex-mediated increase in sympathetic
      nerve activity (SNA), whereas spironolactone exerted central sympathoinhibitory
      action in addition to diuretic effects. OBJECTIVES: The objectives were to
      determine effects of spironolactone and chlorthalidone on SNA and the role of SNA
      on diuretic-induced insulin resistance in human hypertension. METHODS: We
      conducted a randomized crossover study in 23 untreated hypertensive patients in
      which we measured muscle SNA at baseline, after 1 and 3 months of chlorthalidone
      (12.5-25 mg/d), and after 1 and 3 months of spironolactone (50-75 mg/d).
      Ambulatory BP, baroreflex sensitivity, and indices of insulin resistance were
      also assessed at baseline and after 3 months of each drug treatment. RESULTS:
      Chlorthalidone caused a similar reduction in ambulatory BP from baseline when
      compared with spironolactone (11 +/- 2/4 +/- 2 and 10 +/- 2/4 +/- 2 mm Hg,
      respectively). However, chlorthalidone increased SNA by 23% (P < 0.01) within 1
      month of treatment, whereas spironolactone had no effect in the same subjects.
      SNA continued to be elevated after 3 months of chlorthalidone when compared with
      baseline and spironolactone. Baroreflex control of SNA was unaffected by either
      drug. Chlorthalidone increased indices of insulin resistance, which were
      significantly correlated with increases in SNA from baseline, whereas
      spironolactone had no effect in the same subjects. CONCLUSIONS: Our data suggest
      that chlorthalidone, the first-line drug therapy for hypertension, causes
      persistent activation of sympathetic nervous system and insulin resistance in
      hypertensive patients. These side effects, however, are avoided by spironolactone
      despite similar reduction in BP.

PMID- 19158192
TI  - Adrenal glucocorticoid and androgen precursor dissociation in anorexia nervosa.
AB  - CONTEXT: Anorexia nervosa is characterized by hypogonadism and relative
      hypercortisolemia. We have demonstrated that free testosterone levels are low in
      women with anorexia nervosa, with the lowest levels in those receiving oral
      contraceptives (OCPs), and that dehydroepiandrosterone (DHEA) sulfate is reduced
      only in those receiving OCPs. OBJECTIVE: The aim of the study was to determine
      whether adrenal steroidogenesis dysregulation contributes to decreased androgen
      levels in anorexia nervosa. DESIGN AND SETTING: We conducted a cross-sectional
      study in a General Clinical Research Center. STUDY PARTICIPANTS: We studied 20
      women with anorexia nervosa [10 women with anorexia nervosa receiving OCPs (AN+E)
      and 10 not receiving OCPs (AN-E)] and 20 healthy controls [10 healthy controls
      receiving OCPs (HC+E) and 10 not receiving OCPs (HC-E)]. MAIN OUTCOME MEASURES:
      We measured DHEA and cortisol levels in response to 250-microg cosyntropin
      stimulation after 1-mg overnight dexamethasone suppression. RESULTS: Mean basal
      and stimulated, peak stimulated, and area under the curve (AUC) cortisol levels
      were higher in AN-E than HC-E, but mean basal and stimulated, peak and AUC DHEA
      were comparable. Mean AUC and peak cortisol were higher and DHEA AUC was lower in
      AN+E than AN-E. However, after controlling for cortisol binding globulin levels,
      peak and AUC cortisol were comparable between AN+E and AN-E. After controlling
      for albumin levels, AUC DHEA was comparable between AN+E and AN-E. CONCLUSIONS:
      Adrenal glucocorticoid and androgen precursor secretion are dissociated in
      anorexia nervosa, with relative hypercortisolemia and a preservation of DHEA
      secretion. Reduced DHEA response to cosyntropin in women receiving OCPs is
      attributable to decreased albumin levels. In the setting of relative
      hypercortisolemia, reduced adrenal androgen precursor secretion is not a
      mechanism underlying low testosterone levels in anorexia nervosa.

PMID- 19158193
TI  - Extreme longevity is associated with increased serum thyrotropin.
AB  - CONTEXT: The distribution of serum TSH shifts progressively to higher
      concentrations with age. OBJECTIVE: The aim of the study was to determine whether
      the population shift in TSH distribution to higher concentrations with aging
      extends to people of exceptional longevity, namely centenarians, and to assess
      the relationship between concentrations of TSH and free T(4) (FT4).
      DESIGN/SETTING/PATIENTS: We analyzed TSH, FT4, and TSH frequency distribution
      curves in thyroid disease-free Ashkenazi Jews with exceptional longevity
      (centenarians; median age, 98 yr), in younger Ashkenazi controls (median age, 72
      yr), and in a population of thyroid disease-free individuals (median age, 68 yr)
      from the U.S. National Health and Nutrition Examination Survey 1998-2002 (NHANES
      controls). RESULTS: Serum TSH was significantly higher in centenarians [1.97
      (0.42-7.15) mIU/liter] than in Ashkenazi controls [1.55 (0.46-4.55) mIU/liter]
      and NHANES controls [1.61 (0.39-6.29) mIU/liter] (median, 2.5 and 97.5 centiles)
      (P < 0.001). The TSH frequency distribution curve of centenarians was relatively
      similar in shape to controls but shifted significantly to higher TSH, including
      TSH concentration at peak frequency. The TSH distribution curve of the NHANES
      control group was superimposable to and not significantly different from the
      Ashkenazi controls. FT4 was similar in centenarians and Ashkenazi controls, and
      there was a significant inverse correlation between FT4 and TSH in both groups.
      CONCLUSIONS: The TSH population shifts to higher concentrations with age appear
      to be a continuum that extends even to people with exceptional longevity. The
      inverse correlation between TSH and FT4 in our populations suggests that changes
      in negative feedback may contribute to exceptional longevity.

PMID- 19158194
TI  - Retinol-binding protein 4 in polycystic ovary syndrome--association with steroid
      hormones and response to pioglitazone treatment.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is frequently associated with insulin
      resistance. OBJECTIVE: The aim of the study was to investigate a putative role of
      the adipokines retinol-binding protein 4 (RBP4), adiponectin, and visfatin in a
      cohort of patients with PCOS and their response to treatment with pioglitazone.
      DESIGN AND SETTING: We conducted a randomized, controlled, double-blind study at
      a tertiary referral center. PATIENTS AND INTERVENTIONS: Forty premenopausal women
      with PCOS were allocated to receive treatment with either pioglitazone (30 mg/d)
      or a placebo for a period of 3 months. MAIN OUTCOME MEASURES: Serum
      concentrations of RBP4, adiponectin, and visfatin were determined along with
      metabolic and hormonal parameters before and after treatment. RESULTS: Serum
      adiponectin concentrations were higher after treatment with pioglitazone (P =
      0.003), whereas RBP4 levels tended to decrease (P = 0.06), and visfatin
      concentrations remained unchanged. We found RBP4 serum concentrations at baseline
      to be positively correlated with serum levels of testosterone (R = 0.446; P =
      0.005), 17-OH progesterone (R = 0.345, P = 0.037), and dehydroepiandrosterone
      sulfate (R = 0.347; P = 0.041). However, these correlations were abolished after
      treatment with pioglitazone. Patients with high RBP4 levels had significantly
      higher hirsutism scores (P = 0.038 before and P = 0.034 after treatment). In
      contrast, serum adiponectin concentrations were related to parameters of impaired
      glucose metabolism, and no significant associations were detected for visfatin.
      CONCLUSIONS: Our results suggest that RBP4 may contribute to endocrine changes
      and to the phenotypic manifestation of patients with PCOS because higher RBP4
      concentrations are associated with higher androgen levels and higher clinical
      hirsutism scores independently of pioglitazone treatment. The molecular
      involvement of RBP4 in human steroid metabolism requires further clarification.

PMID- 19158195
TI  - Nuclear accumulation of e-cadherin correlates with loss of cytoplasmic membrane
      staining and invasion in pituitary adenomas.
AB  - CONTEXT: Loss of the cell adhesion protein E-cadherin is associated with invasion
      and metastasis in a number of malignancies. Recent studies have highlighted that
      loss of E-cadherin cell membrane expression may be accompanied by its detection
      in the nucleus, suggesting cellular redistribution during neoplasia. Pituitary
      tumors, although typically benign, may be locally invasive, and loss of
      membranous E-cadherin has been reported as a marker of invasion in prolactinomas.
      OBJECTIVE: Our objective was to study E-cadherin expression in pituitary
      adenomas, specifically whether nuclear redistribution occurs in this setting.
      METHODS: Immunohistochemistry, RT-PCR, and direct sequencing were performed.
      RESULTS: Strong cytoplasmic membrane staining was present in all eight normal
      samples but completely absent in 21 of 44 adenomas (48%) with weak staining in an
      additional 11 adenomas using an antibody against the extracellular domain of E
      cadherin. To identify nuclear translocation of the protein, immunohistochemistry
      was performed using an antibody against the cytoplasmic domain. Nuclear staining
      was present in 38 of 44 adenomas (86%) and absent in normal tissue. Nuclear E
      cadherin inversely correlated with loss of E-cadherin cytoplasmic membrane
      staining and was associated with tumor invasion (P = 0.009). To investigate the
      mechanism of nuclear redistribution of E-cadherin, we performed RT-PCR of mRNA
      and sequenced tumor DNA. E-cadherin mRNA expression was reduced in only one of 30
      samples (3%). No mutations were detected. CONCLUSIONS: E-cadherin was frequently
      lost at the cytoplasmic membrane but detected in the nucleus, suggesting that
      cleavage of the extracellular domain and nuclear translocation of E-cadherin is a
      common event that may determine local invasion in pituitary adenomas.

PMID- 19158196
TI  - Cortisol inactivation by 11beta-hydroxysteroid dehydrogenase-2 may enhance
      endometrial angiogenesis via reduced thrombospondin-1 in heavy menstruation.
AB  - CONTEXT: Heavy menstrual bleeding (HMB; menorrhagia) impairs quality of life for
      women and requires medication or surgery. Because glucocorticoids inhibit
      angiogenesis in other organs, we hypothesized that endometrium of women with HMB
      is subject to decreased local glucocorticoid exposure and enhanced angiogenesis,
      thereby increasing menstrual bleeding. DESIGN: Endometrium was collected from 29
      women with menstrual complaints. Menstrual blood loss was measured by alkaline
      hematin assay (n = 12, > 80 ml (HMB); n = 17, < 80 ml). Quantitative RT-PCR for
      thrombospondin-1 (TSP-1) and glucocorticoid-metabolizing enzymes, 11beta
      hydroxysteroid dehydrogenases-1 and -2 (11betaHSD1,2) was performed.
      Glucocorticoid effects on endometrial stromal cells and uterine endothelial cells
      (UECs) were determined. RNA interference studies in UECs examined the effect of
      TSP-1 ablation on cortisol action. RESULTS: Secretory phase endometrium mRNA
      levels for the cortisol inactivating enzyme 11betaHSD2 were higher [3.78 +/- 1.29
      vs. 1.40 +/- 0.6 (arbitrary units), P < 0.05], whereas TSP-1 mRNA was lower [0.40
      +/- 0.13 vs. 1.66 +/- 1.02 (arbitrary units), P < 0.05] in women with HMB. In
      cultured endometrial stromal cells and UECs, cortisol increased TSP-1 expression.
      Both cortisol and TSP-1 inhibited new vessel formation in endometrial explants
      embedded in Matrigel. In UECs cortisol inhibition of tube-like structure
      formation was blocked by small interfering RNA (siRNA) against TSP-1 (25 +/- 2.5%
      cortisol inhibition with scrambled siRNA vs. 0% cortisol inhibition with TSP-1
      siRNA inactivation, P<0.01). CONCLUSIONS: Enhanced inactivation of cortisol by
      11betaHSD2 in endometrium from women with HMB may explain reduced TSP-1 levels
      and hence endothelial cell dysfunction and abnormal angiogenesis. Inhibition of
      11betaHSD2 may be a rational novel therapy for heavy menstrual bleeding.

PMID- 19158197
TI  - Randomized controlled trial to investigate the effects of growth hormone
      treatment on scoliosis in children with Prader-Willi syndrome.
AB  - CONTEXT: The prevalence of scoliosis in children with Prader-Willi syndrome (PWS)
      is 30-80%, depending on age. Although reports about effects of GH treatment on
      scoliosis in children with PWS are limited, scoliosis is generally considered a
      contraindication for GH treatment. OBJECTIVE: The aim was to study the effects of
      GH treatment on the onset of scoliosis and curve progression in children with
      PWS. DESIGN: We conducted a multicenter, randomized, controlled GH study in
      infants and prepubertal and pubertal children. Infants and prepubertal children
      were randomized into a GH-treated group (1.0 mg/m(2) . d) and a control group for
      1 and 2 yr, respectively. Pubertal children were randomized to receive somatropin
      1.0 or 1.5 mg/m(2) . d. Yearly, x-rays of the spine were taken, and height,
      weight, truncal lean body mass (with dual energy x-ray absorptiometry), and IGF-I
      were measured. PATIENTS: A total of 91 children with PWS (median age, 4.7 yr;
      interquartile range, 2.1-7.4) participated in the study. MAIN OUTCOME MEASURES:
      We measured the onset of scoliosis (Cobb >10 degrees ) and scoliotic curve
      progression. RESULTS: GH-treated children had similar onset of scoliosis and
      curve progression as randomized controls (P = 0.27-0.79 and P = 0.18-0.98,
      respectively). GH treatment, IGF-I sd score (SDS), and catch-up growth had no
      adverse effect on the onset of scoliosis or curve progression, even after
      adjustment for confounders. Height SDS, truncal lean body mass, and IGF-I SDS
      were significantly higher in GH-treated children than in randomized controls. At
      baseline, a higher IGF-I SDS was associated with a lower severity of scoliosis.
      CONCLUSIONS: Scoliosis should no longer be considered a contraindication for GH
      treatment in children with PWS.

PMID- 19158198
TI  - Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum
      parathyroid hormone and markers of bone turnover in older persons.
AB  - CONTEXT: Serum 25-hydroxyvitamin D [25(OH)D] may influence serum PTH and other
      parameters of bone health up to a threshold concentration, which may be between
      25 and 80 nmol/liter. OBJECTIVE: The aim of the study was to assess the threshold
      serum 25(OH)D with regard to PTH, bone turnover markers, and bone mineral density
      (BMD). DESIGN AND SETTING: This was part of the Longitudinal Aging Study
      Amsterdam, an ongoing cohort study. PARTICIPANTS: A total of 1319 subjects (643
      men and 676 women) between the ages of 65 and 88 yr participated in the study.
      MAIN OUTCOME MEASURES: Serum 25(OH)D, PTH, osteocalcin, urinary
      deoxypyridinoline/creatinine, quantitative ultrasound of the heel, BMD of lumbar
      spine and hip, total body bone mineral content, and physical performance. The
      relationship between the variables was explored by analysis of covariance and the
      locally weighted regression (LOESS) plots. RESULTS: Serum 25(OH)D was below 25
      nmol/liter in 11.5%, below 50 nmol/liter in 48.4%, below 75 nmol/liter in 82.4%,
      and above 75 nmol/liter in 17.6% of the respondents. Mean serum PTH decreased
      gradually from 5.1 pmol/liter when serum 25(OH)D was below 25 nmol/liter to 3.1
      pmol/liter when serum 25(OH)D was above 75 nmol/liter (P < 0.001) without
      reaching a plateau. All BMD values were higher in the higher serum 25(OH)D
      groups, although only significantly for total hip (P = 0.01), trochanter (P =
      0.001), and total body bone mineral content (P = 0.005). A threshold of about 40
      nmol/liter existed for osteocalcin and deoxypyridinoline/creatinine, 50
      nmol/liter for BMD, and 60 nmol/liter for physical performance. CONCLUSIONS: Low
      serum 25(OH)D concentrations are common in the elderly. Bone health and physical
      performance in older persons are likely to improve when serum 25(OH)D is raised
      above 50-60 nmol/liter.

PMID- 19158199
TI  - TSHR mutations as a cause of congenital hypothyroidism in Japan: a population
      based genetic epidemiology study.
AB  - CONTEXT: The prevalence of congenital hypothyroidism (CH) associated with
      mutations in the TSH receptor gene (TSHR) has not been established. OBJECTIVE: We
      examined the frequency of TSHR mutations among patients with permanent primary CH
      and in the general population in Japan. SUBJECTS AND METHODS: We enrolled 102
      patients with permanent primary CH [70 with "moderate to severe CH" (TSH, >or=10
      mU/liter) and 32 with "mild CH" (TSH, 5-10 mU/liter)], who were identified
      through newborn screening among 353,000 newborns born in Kanagawa prefecture from
      October 1979 to June 2006. These subjects were tested for TSHR mutations by PCR
      based direct sequencing. We further characterized molecular functions of
      identified mutant TSHRs in vitro. RESULTS: We found three patients with moderate
      to severe CH who had biallelic mutations in TSHR and three patients with mild CH
      who had monoallelic mutations. Observed mutations included one previously
      characterized mutation (p.R450H) and three uncharacterized mutations (p.G132R,
      p.A204V, and p.D403N). In vitro experiments confirmed loss of functions of these
      four mutants. Among four mutations, p.R450H was particularly frequent: six of
      nine mutant alleles harbored p.R450H. All six alleles with p.R450H commonly
      carried a minor single nucleotide polymorphism, suggesting a founder effect. We
      estimated the prevalence of biallelic TSHR mutations to be 4.3% (three in 70) in
      Japanese patients with moderate to severe CH, and 1 in 118,000 (three in 353,000)
      in the general Japanese population. CONCLUSIONS: In Japan, TSHR mutations are
      relatively common among patients with CH, and a founder mutation (p.R450H)
      accounts for about 70% of mutants.

PMID- 19158200
TI  - Assessment of the incremental value of recombinant thyrotropin stimulation before
      2-[18F]-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography
      imaging to localize residual differentiated thyroid cancer.
AB  - PURPOSE: The purpose of the study was to assess prospectively the impact of
      recombinant human TSH (rhTSH) administration on positron emission tomography
      (PET)/computed tomography (CT) imaging in differentiated thyroid cancer patients
      who, after primary treatment, had a suppressed or stimulated serum thyroglobulin
      greater than 10 ng/ml and no radioactive iodine uptake consistent with thyroid
      cancer on a whole body scan. PATIENTS AND METHODS: PET/CT was performed before
      (basal PET) and 24-48 h after rhTSH administration (rhTSH-PET) in 63 patients (52
      papillary and 11 follicular thyroid cancers). Images were blindly analyzed by two
      readers. The proposed treatment plan was prospectively assessed before basal PET,
      after basal PET, and again after rhTSH-PET. RESULTS: A total of 108 lesions were
      detected in 48 organs in 30 patients. rhTSH-PET was significantly more sensitive
      than basal PET for the detection of lesions (95 vs. 81%; P = 0.001) and tended to
      be more sensitive for the detection of involved organs (94 vs. 79%; P = 0.054).
      However, basal PET and rhTSH-PET did not have significantly different sensitivity
      for detecting patients with any lesions (49 vs. 54%; P = 0.42). Changes in
      treatment management plan occurred in 19% of the patients after basal PET.
      Lesions found only by rhTSH-PET contributed to an altered therapeutic plan in
      eight patients, among whom only four were true-positive on pathology (6%).
      CONCLUSION: The use of rhTSH for 2-[18F]-fluoro-2-deoxy-D-glucose-PET/CT
      significantly increased the number of lesions detected, but the numbers of
      patients in whom any lesion was detected were no different between basal and
      rhTSH-stimulated PET/CT scans. Treatment changes due to true positive lesions
      occurred in 6% of cases.

PMID- 19158201
TI  - Gonadal function, first cases of pregnancy, and child delivery in a woman with
      lipoid congenital adrenal hyperplasia.
AB  - CONTEXT: Mutations in the steroidogenic acute regulatory protein (StAR) gene
      often cause lipoid congenital adrenal hyperplasia (LCAH). In this disorder an
      impairment of steroid synthesis leads to adrenal and gonadal insufficiencies with
      a particular female genital phenotype in both human karyotypes. Pregnancy in LCAH
      has not been yet reported. OBJECTIVE: We describe the first cases of pregnancy in
      a LCAH female patient bearing the L275P mutation in the StAR gene. DESIGN: We
      studied the gonadal function, pubertal development, and apply the appropriate
      hormonal therapy to support pregnancies. PATIENT: A 46,xx patient of French
      Canadian descent was diagnosed with LCAH at the age of 4.5 months. Substitution
      therapy with glucocorticoids and mineralocorticoids led to normal growth and
      development. Progressive pubertal development started at the age of 11 7/12 yr.
      Menarche occurred at 14 2/12 yr with normal regular menstruations thereafter but
      without ovulation. RESULTS: Clomiphene stimulation induced the first pregnancy at
      25 4/12 yr of age. Spontaneous abortion occurred after 6 wk gestation. The second
      pregnancy (with clomiphene stimulation) was induced at the age of 26 yr.
      Progesterone (Prog) therapy was added at the 17th day of the cycle to protect
      pregnancy. Vaginal delivery of dichorionic-diamniotic twin pregnancy occurred at
      30 wk gestation (two normal weight male babies). Two years later, again under
      clomiphene stimulation, she underwent another successful singleton pregnancy and
      delivered a normal weight female baby at 36 wk. The pregnancies were almost
      uncomplicated. CONCLUSION: Despite the dysfunctional StAR, pregnancy is possible
      under the proper therapeutic strategy.

PMID- 19158202
TI  - Insulin-like growth factor-binding protein-1: serum levels, promoter
      polymorphism, and associations with components of the metabolic syndrome in short
      subjects born small for gestational age.
AB  - CONTEXT: IGF binding protein (IGFBP)-1 is the only acute regulator of IGF-I
      bioavailability. Its production is suppressed by insulin, and low levels are
      associated with hyperinsulinemia and cardiovascular disease risk in adults. Data
      on IGFBP-1 levels in short, small for gestational age (SGA) subjects are scarce,
      and associations with IGFBP1 promoter single nucleotide polymorphisms have not
      been established. OBJECTIVE: The aim of the study was to determine IGFBP-1 levels
      in short SGA subjects compared with those in controls, to assess genotype
      frequency of the -575 G/A single nucleotide polymorphism, and to determine its
      impact on IGFBP-1 levels. SUBJECTS: A total of 272 short subjects born SGA and
      330 subjects with normal stature (245 children, 85 young adults) participated in
      the study. OUTCOME MEASURES: We measured fasting levels of IGFBP-1, IGF-I,
      insulin and lipid parameters, and body composition. RESULTS: IGFBP-1 sd score
      (SDS) was comparable to controls in lean, short, SGA children but significantly
      lower in short SGA adults with normal fat mass (P < 0.001). IGFBP-1 SDS
      correlated significantly with insulin levels, systolic blood pressure SDS, and
      various lipid parameters. Baseline IGFBP-1 SDS was lowest in SGA children with 
      575 GG genotype and significantly higher in SGA children with one or two copies
      of the A allele. In response to a given insulin level, children with the AA
      genotype had a significantly higher IGFBP-1 SDS compared to children with the GG
      genotype. CONCLUSION: Normal IGFBP-1 levels in lean, short, SGA children may
      reflect a normal metabolic state, despite reported hyperinsulinemia. IGFBP-1 is
      modulated by polymorphic variability and seems to be an additional player in the
      complex interaction between the IGF-IGFBP axis, glucose homeostasis, and lipid
      metabolism.

PMID- 19158203
TI  - Medical therapy in patients with acromegaly: predictors of response and
      comparison of efficacy of dopamine agonists and somatostatin analogues.
AB  - CONTEXT: Acromegaly is associated with increased morbidity and mortality.
      Treatment options include surgery, radiotherapy, and medical therapy. AIMS: The
      objective of the study was to examine the role of prolactin status, prior
      surgery, and radiotherapy on the response to medical therapy in patients with
      acromegaly and assess the relative efficacy of dopamine agonist therapy compared
      with somatostatin analog therapy. MATERIALS AND METHODS: A total of 276 patients
      with acromegaly received either dopamine agonists (DA) and/or somatostatin
      analogs (SSA). One hundred seventy-two patients had received surgery and 73
      radiotherapy prior to receiving medical therapy. One hundred ninety-eight of 276
      received DA, and 143 of 276 received SSA. GH and IGF-I values at baseline and
      after 12 months on therapy were analyzed. RESULTS: In the DA group, basal
      prolactin concentration did not predict response to therapy, GH percent
      reduction: hyperprolactinemia, 26.7% (-10.4 to 48) vs. normoprolactinemia, 34.8%
      (0.2-53.2), P = 0.58; IGF-I percent reduction: hyperprolactinemia 30.0% (9.2
      43.1) vs. normoprolactinemia 16.8% (4-37), P = 0.45. Prior surgery was not
      associated with any difference in response to DA: GH percent reduction (P = 0.1)
      and IGF-I percent reduction (P = 0.08). By contrast, prior radiotherapy was
      associated with an enhanced efficacy of GH response to DA, P = 0.02. In the SSA
      group, there was no effect of prior surgery or radiotherapy on response of GH,
      but radiotherapy was associated with less marked IGF-I percent reduction (P =
      0.05). SSA were more potent than DA at decreasing both GH [62.8% (20.7-85%) vs.
      42.4% (-6.5 to 68.6), P < 0.008] and IGF-I [SSA 40.4% (0-64.3) vs. 8% (0-40.8), P
      = 0.05]. CONCLUSIONS: The effects of DA are irrespective of baseline prolactin
      concentrations. Prior radiotherapy is associated with differences in GH and IGF-I
      response to DA and SSA therapy.

PMID- 19158204
TI  - Scavenger receptor class B type I protein as an independent predictor of high
      density lipoprotein cholesterol levels in subjects with
      hyperalphalipoproteinemia.
AB  - CONTEXT: In mice, scavenger receptor class B, type I (SR-BI) receptor protein
      deficiency is associated with elevated high-density lipoprotein (HDL)-cholesterol
      (HDL-C) levels. OBJECTIVE: Our objective was to determine the relationship
      between SR-BI protein and HDL-C levels in humans. DESIGN: This was a prospective
      study of adults with hyperalphalipoproteinemia. Fasting blood was obtained for
      lipid and lipoprotein measurement, genomic DNA, and monocyte-derived macrophages.
      SR-BI protein levels were measured by Western blots, and SR-BI activity was
      measured by cholesteryl ester (CE) uptake of each donor's radiolabeled HDL with
      their monocyte-derived macrophages, or by degradation and specific cell
      association of dual-labeled HDL in vitro. SETTING: The study was performed in a
      tertiary university teaching hospital. RESULTS: The mean age was 57.2 +/- 10.9 yr
      (n = 65). SR-BI protein levels were inversely associated with HDL-C levels (P <
      0.002), HDL particle size (P < 0.05), and positively associated with CE uptake (P
      < 0.004); there was no association with plasma apolipoprotein levels. SR-BI
      protein levels (P = 0.01) were independent predictors of HDL-C levels. Subjects
      who were carriers of the A allele for the rs4238001 (glycine to serine at
      position 2) polymorphism [single nucleotide polymorphism (SNP)] had lower SR-BI
      protein levels (P = 0.01), whereas carriers of the C allele for the rs2278986 SNP
      also had lower SR-BI protein levels (P = 0.02). Body mass index (P = 0.05),
      rs4238001 (P = 0.01), and rs2278986 (P = 0.01) SNPs were independent predictors
      of SR-BI protein levels. In vitro studies of murine macrophages stably expressing
      the glycine to serine at position 2 SNP showed less degradation (P < 0.0004) and
      specific cell association (P < 0.0004) of [(125)I, (3)H]-CE-labeled HDL.
      CONCLUSIONS: SR-BI protein has an independent effect on HDL-C levels in women
      with hyperalphalipoproteinemia. Two SNPs were significantly associated with lower
      SR-BI protein levels.

PMID- 19158205
TI  - FTO genotype is associated with body mass index after the age of seven years but
      not with energy intake or leisure-time physical activity.
AB  - CONTEXT: A common variant in the FTO gene, rs9939609, associates with body mass
      index (BMI) in adults and in children aged 7 yr or older. OBJECTIVE: Our aim was
      to examine the associations of the FTO genotype with BMI, cardiovascular risk
      factors, energy intake, and leisure-time physical activity in children followed
      up since infancy. METHODS: Healthy participants of the STRIP Study, genotyped for
      rs9939609, were followed from age 7 months (n = 640) to 15 yr (n = 438). The
      children were randomly assigned to lifestyle intervention and control groups.
      Height, weight, blood pressure, and serum lipids were measured annually. Food
      records and physical activity index were obtained at age 15 yr. RESULTS: The FTO
      genotype did not associate with BMI in children younger than 7 yr of age. From
      age 7 yr onward, the children homozygous for the A allele had progressively
      higher BMI than the children with one or two T alleles (P = 0.029 for FTO by age
      interaction). Furthermore, in longitudinal, BMI Z-score-adjusted analysis, the AA
      genotype associated with higher systolic and diastolic blood pressure and with
      elevated serum total and low-density lipoprotein-cholesterol (P = 0.01, P <
      0.001, P = 0.05, and P = 0.04 for main effect, respectively). The FTO genotype
      did not associate with energy intake or physical activity index at age 15. The
      FTO *Study group interactions were not significant. CONCLUSIONS: Our results
      suggest that the effect of the FTO genotype on BMI becomes evident only after age
      7 yr. These results further suggest that the FTO gene is not directly associated
      with energy intake or physical activity.

PMID- 19158206
TI  - Atomic-resolution spectroscopic imaging: past, present and future.
AB  - This review examines the development of atomically resolved electron energy loss
      spectroscopy from the first demonstration of plane-by-plane compositional
      profiling, through column-by-column spectroscopy to full two-dimensional and
      potentially three-dimensional spectroscopic imaging. Examples will be presented
      to highlight the increasing analytical sensitivity and image contrast obtained
      through each generation of aberration correction, moving towards the ultimate
      goal of mapping electronic structure inside materials with atomic resolution.

PMID- 19158207
TI  - Chronic intake of potato chips in humans increases the production of reactive
      oxygen radicals by leukocytes and increases plasma C-reactive protein: a pilot
      study.
AB  - BACKGROUND: Relatively high concentrations of acrylamide in commonly ingested
      food products, such as French fries, potato chips, or cereals, may constitute a
      potential risk to human health. OBJECTIVE: The objective of this pilot study was
      to investigate the possible connection between chronic ingestion of acrylamide
      containing potato chips and oxidative stress or inflammation. DESIGN: Fourteen
      healthy volunteers (mean age: 35 y; 8 women and 6 smokers of >20 cigarettes/d)
      were given 160 g of potato chips containing 157 microg [corrected] acrylamide
      daily for 4 wk. RESULTS: An increase in acrylamide-hemoglobin adducts in blood
      was found in all the study subjects, with a mean of 43.1 pmol x L(-1) x g(-1)
      hemoglobin (range: 27-76; P < 0.01) in nonsmokers and 59.0 pmol x L(-1) x g(-1)
      hemoglobin (range: 43-132; P < 0.05) in smokers. Concurrently, a significant
      increase (P < 0.01) in the oxidized LDL, high-sensitivity interleukin-6, high
      sensitivity C-reactive protein, and gamma-glutamyltransferase concentrations was
      observed in both smokers and nonsmokers. A significant increase in reactive
      oxygen radical production by monocytes, lymphocytes, and granulocytes and an
      increase in CD14 expression in macrophages (P < 0.001) were found after intake of
      potato chips. Twenty-eight days from the discontinuation of the experiment, the
      variables under study decreased to some extent. It has been shown also that
      acrylamide increases the production of reactive oxygen species in isolated human
      monocyte-macrophages in vitro and decreases the cellular glutathione
      concentration. CONCLUSION: These novel findings seem to indicate that chronic
      ingestion of acrylamide-containing products induces a proinflammatory state, a
      risk factor for progression of atherosclerosis.

PMID- 19158209
TI  - Effects of 1 and 3 g cinnamon on gastric emptying, satiety, and postprandial
      blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon
      like peptide 1, and ghrelin concentrations in healthy subjects.
AB  - BACKGROUND: A previous study of healthy subjects showed that intake of 6 g
      cinnamon with rice pudding reduced postprandial blood glucose and the gastric
      emptying rate (GER) without affecting satiety. OBJECTIVE: The objective was to
      study the effect of 1 and 3 g cinnamon on GER, postprandial blood glucose, plasma
      concentrations of insulin and incretin hormones [glucose-dependent insulinotropic
      polypeptide (GIP) and glucagon-like peptide 1 (GLP-1)], the ghrelin response, and
      satiety in healthy subjects. DESIGN: GER was measured by using real-time
      ultrasonography after ingestion of rice pudding with and without 1 or 3 g
      cinnamon. Fifteen healthy subjects were assessed in a crossover trial. RESULTS:
      The addition of 1 or 3 g cinnamon had no significant effect on GER, satiety,
      glucose, GIP, or the ghrelin response. The insulin response at 60 min and the
      area under the curve (AUC) at 120 min were significantly lower after ingestion of
      rice pudding with 3 g cinnamon (P = 0.05 and P = 0.036, respectively, after
      Bonferroni correction). The change in GLP-1 response (DeltaAUC) and the change in
      the maximum concentration (DeltaC(max)) were both significantly higher after
      ingestion of rice pudding with 3 g cinnamon (P = 0.0082 and P = 0.0138,
      respectively, after Bonferroni correction). CONCLUSIONS: Ingestion of 3 g
      cinnamon reduced postprandial serum insulin and increased GLP-1 concentrations
      without significantly affecting blood glucose, GIP, the ghrelin concentration,
      satiety, or GER in healthy subjects. The results indicate a relation between the
      amount of cinnamon consumed and the decrease in insulin concentration.

PMID- 19158208
TI  - Dietary intake of selected flavonols, flavones, and flavonoid-rich foods and risk
      of cancer in middle-aged and older women.
AB  - BACKGROUND: Flavonoids may protect against cancer development through several
      biological mechanisms. However, epidemiologic studies on dietary flavonoids and
      cancer risk have yielded inconsistent results. OBJECTIVE: We prospectively
      investigated the association between the intake of selected flavonoids and
      flavonoid-rich foods and risk of cancers in the Women's Health Study. DESIGN: A
      total of 3234 incident cancer cases were identified during 11.5 y of follow-up
      among 38,408 women aged > or = 45 y. Intake of individual flavonols (quercetin,
      kaempferol, and myricetin) and flavones (apigenin and luteolin) was assessed from
      food-frequency questionnaires. Cox regression models were used to estimate the
      relative risk (RR) of total and site-specific cancer across increasing intakes of
      total and individual selected flavonoids and flavonoid-rich foods (tea, apple,
      broccoli, onion, and tofu). RESULTS: The multivariate RRs of total cancer across
      increasing quintiles of total quantified flavonoid intake were 1.00, 1.00, 0.93,
      0.94, and 0.97 (P for trend = 0.72). For site-specific cancers, the multivariate
      RRs in the highest quintile of total quantified flavonoid intake compared with
      the lowest quintile were 1.03 for breast cancer, 1.01 for colorectal cancer, 1.03
      for lung cancer, 1.15 for endometrial cancer, and 1.09 for ovarian cancer (all P
      > 0.05). The associations for the individual flavonoid intakes were similar to
      those for the total intake. There was also no significant association between
      intake of flavonoid-rich foods and the incidence of total and site-specific
      cancers. CONCLUSION: Our results do not support a major role of 5 common
      flavonols and flavones or selected flavonoid-rich foods in cancer prevention.

PMID- 19158210
TI  - Iron deficiency and child and maternal health.
AB  - BACKGROUND: Iron deficiency is most commonly found in women of reproductive age
      and infants worldwide, but the influence of maternal iron deficiency on infant
      development is underexplored. OBJECTIVE: The objective was to examine the
      relation between maternal iron status and mother-child interactions in a
      randomized, double-blind, intervention trial conducted in South Africa. DESIGN:
      Women were recruited into the study from a health clinic at 6-8 wk postpartum and
      were classified as either iron-deficient anemic (IDA) or iron-sufficient after
      blood analysis. IDA mothers received iron supplements of 125 mg FeSO(4) (IDA-Fe;
      n = 34) or placebo (IDA-PL; n = 30) daily from 10 wk to 9 mo postpartum. The
      control group (n = 31) consisted of iron-sufficient mothers. Free-play mother
      child interaction sessions were videotaped in the clinic at 10 wk (n = 80) and 9
      mo (n = 66) postpartum and coded per the Emotional Availability Scales (4
      maternal scales: sensitivity, structuring, nonintrusiveness, and nonhostility; 2
      infant scales: responsiveness and involvement). RESULTS: At 10 wk, scores for
      maternal sensitivity and child responsiveness were significantly greater in the
      control group than in the IDA groups (P = 0.028 and 0.009, respectively). At 9
      mo, the control and IDA-Fe groups no longer differed. These 2 groups scored
      significantly better on the maternal sensitivity, structuring, and nonhostility
      scales and on the child responsiveness scale than did the IDA-PL group (P = 0.007
      0.032), whose iron status remained low. CONCLUSION: These data indicate that
      maternal iron deficiency negatively affects mother-child interactions and that
      iron supplementation protects against these negative effects.

PMID- 19158211
TI  - Steady state folate concentrations achieved with 5 compared with 1.1 mg folic
      acid supplementation among women of childbearing age.
AB  - BACKGROUND: Synthetic folic acid (0.4-1.0 mg) consumed during the
      periconceptional period has been shown to reduce the risk of neural tube defects.
      Women with poor supplement adherence or a previous pregnancy affected by a neural
      tube defect may need to take higher doses of folic acid (4-5 mg). However, there
      are limited data on the pharmacokinetics of higher folic acid doses. OBJECTIVE:
      Our aim was to compare steady state folate concentrations in women of
      childbearing age who took 5 or 1.1 mg folic acid daily for 30 wk. DESIGN: Forty
      nonpregnant women aged between 18 and 45 y, who did not take folic acid
      supplements, were enrolled in the study. Subjects were randomly assigned to take
      either 5 or 1.1 mg folic acid daily for 30 wk. Plasma and red blood cell (RBC)
      folate concentrations were measured at baseline and at weeks 2, 4, 6, 12, and 30.
      RESULTS: There was no significant difference in baseline RBC folate
      concentrations between the 2 groups (1121 +/- 410 and 1035 +/- 273 nmol/L for the
      5- and 1.1-mg folic acid groups, respectively). Significant differences in RBC
      folate were detected between groups at weeks 4, 6, 12, and 30. RBC folate
      concentrations by week 30 were 2339 +/- 782 and 1625 +/- 339 nmol/L for the 5-
      and 1.1-mg folic acid groups, respectively. CONCLUSION: The use of 5 mg folic
      acid among women of childbearing age produced higher blood folate concentrations,
      with a faster rate of folate accumulation, compared with 1.1 mg folic acid.

PMID- 19158212
TI  - Morning ghrelin concentrations are not affected by short-term overfeeding and do
      not predict ad libitum food intake in humans.
AB  - BACKGROUND: Ghrelin has a short-term orexigenic effect but may also be a marker
      of food intake over time. We previously found an inverse association between
      ghrelin concentrations and food intake. OBJECTIVES: The objectives were to
      determine whether the fasting plasma ghrelin concentration is related to food
      intake and whether the previous day's intake predicts the suppression of ghrelin.
      DESIGN: Sixty-nine nondiabetic adults (40 men) aged 33 +/- 9 y were studied as
      inpatients at a Clinical Research Center. After 6 d of consuming a maintenance
      diet, the subjects self-selected their food from our vending machine system for 3
      d. Total plasma ghrelin concentrations were measured every morning during the
      vending machine period. RESULTS: The fasting ghrelin concentration was negatively
      correlated with body mass index (r = -0.31, P = 0.016) and weight (r = -0.26, P =
      0.044). Mean morning ghrelin concentrations remained constant (149 +/- 59, 152 +/
      60, 148 +/- 61, and 145 +/- 59 pg/mL on days 1, 2, 3, and 4, respectively) even
      though the subjects overate while using the vending machines (160 +/- 42% of
      weight-maintenance needs). No associations were found between daily ghrelin
      concentrations and subsequent food intake on any day (day 1: r = -0.04, P = 0.76;
      day 2: r = -0.01, P = 0.95; day 3: r = -0.11, P = 0.38). Suppression of total
      ghrelin concentrations was not associated with the previous day's intake or with
      subsequent food intake. CONCLUSION: Morning plasma ghrelin concentrations do not
      affect acute increases in food intake. This trial was registered at
      clinicaltrials.gov as NCT00342732.

PMID- 19158213
TI  - Adipose tissue distribution is different in type 2 diabetes.
AB  - BACKGROUND: The extent to which adipose tissue (AT) distribution is different
      between persons with type 2 diabetes (T2DM) and nondiabetic control subjects
      remains unclear. OBJECTIVE: The aim of this study was to establish whether total
      body adiposity and its distribution, quantified by using state-of-the-art whole
      body magnetic resonance imaging, differs between these 2 groups. DESIGN: This
      cross-sectional evaluation included 93 participants (n = 56 women and 37 men) in
      the Look AHEAD (Action for HEAlth in Diabetes) Trial with T2DM who had a mean (+/
      SD) age of 58.3 +/- 6.6 y and body mass index (in kg/m(2)) of 31.6 +/- 3.1 and 93
      healthy non-T2DM control subjects (n = 64 women and 29 men) who had a mean (+/
      SD) age of 60.6 +/- 17.1 y and body mass index of 29.6 +/- 3.0. All participants
      self-reported being of African American or white ancestry. Magnetic resonance
      imaging-derived in vivo measures of total-body AT (TAT) and its distribution,
      subcutaneous AT (SAT), visceral AT (VAT), and intermuscular AT (IMAT) were
      acquired. Linear regression models were developed for each AT compartment to
      adjust for important covariates of race, sex, age, height, and weight and to
      examine potential interactions of covariates. RESULTS: These models showed
      significantly less SAT (African American: -1.2 kg; white: -2.4 kg; both P =
      0.001), including less femoral-gluteal SAT, more VAT (African American: 0.7 kg, P
      < 0.001; white: 1.8 kg, P = 0.007), and more IMAT (0.5 kg, P = 0.001) in the T2DM
      group. CONCLUSION: We concluded that AT distribution is significantly altered in
      T2DM, ie, more VAT and IMAT--2 depots known to exacerbate insulin resistance--and
      less SAT in persons with T2DM than in healthy control subjects, a novel finding
      that we posit may compound the risk of insulin resistance.

PMID- 19158214
TI  - Fruit, vegetable, and fish consumption and heart rate variability: the Veterans
      Administration Normative Aging Study.
AB  - BACKGROUND: Higher intakes of fruit, vegetables, and dark fish may prevent sudden
      cardiac death and arrhythmias, but the exact mechanisms are not fully understood.
      OBJECTIVE: We examined whether high consumption of fruit, vegetables, and dark
      fish would be associated with beneficial changes in heart rate variability (HRV).
      DESIGN: HRV variables were measured among 586 older men with 928 total
      observations from November 2000 to June 2007 in the Normative Aging Study, a
      community-based longitudinal study of aging. Dietary intake was evaluated with a
      self-administered semiquantitative food-frequency questionnaire and categorized
      into quartiles. RESULTS: After controlling for potential confounders, intake of
      green leafy vegetables was positively associated with normalized high-frequency
      power and inversely associated with normalized low-frequency power (P for trend <
      0.05). These significant associations were retained after further adjustment for
      healthy lifestyle factors, such as physical activity and use of multivitamins. No
      significant association was seen between HRV measures and intakes of other fruit
      and vegetables, vitamin C, carotenoids, tuna and dark-meat fish, or n-3 (omega-3)
      fatty acids. An effect modification of intake of noncitrus fruit by obesity and
      of total vegetables and cruciferous vegetables by cigarette smoking was seen,
      which warrants further investigation. CONCLUSION: These findings suggest that
      higher intake of green leafy vegetables may reduce the risk of cardiovascular
      disease through favorable changes in cardiac autonomic function.

PMID- 19158215
TI  - Meta-analysis of the quantity of calcium excretion associated with net acid
      excretion: caution advised.

PMID- 19158216
TI  - (n-3) Fatty acid content of red blood cells does not predict risk of future
      cardiovascular events following an acute coronary syndrome.
AB  - A reduced risk of fatal coronary artery disease has been associated with a high
      intake of (n-3) fatty acids (FA) and a direct cardioprotective effect by their
      incorporation into myocardial cells has been suggested. Based on these
      observations, the omega-3 index (eicosapentaenoic acid + docosahexaenoic acid in
      cell membranes of RBC expressed as percent of total FA) has been suggested as a
      new risk marker for cardiac death. In this study, our aim was to evaluate the
      omega-3 index as a prognostic risk marker following hospitalization with an acute
      coronary syndrome (ACS). The omega-3 index was measured at admission in 460
      patients with an ACS as defined by Troponin-T (TnT) > or = 0.02 microg/L. During
      a 2-y follow-up, recurrent myocardial infarctions (MI) (defined as TnT > 0.05
      microg/L with a typical MI presentation) and cardiac and all-cause mortality were
      registered. Cox regression analyses were used to relate the risk of new events to
      the quartiles of the omega-3 index at inclusion. After correction for age, sex,
      previous heart disease, hypertension, diabetes, smoking, high-sensitivity C
      reactive protein, brain natriuretic peptide, creatinine, total cholesterol, HDL
      cholesterol, triacylglycerol, homocysteine, BMI, and medication, there was no
      significant reduction in risk for all-cause mortality, cardiac death, or MI with
      increasing values of the index. In conclusion, we could not confirm the omega-3
      index as a useful prognostic risk marker following an ACS.

PMID- 19158218
TI  - Vegetable but not fruit intake during pregnancy is associated with newborn
      anthropometric measures.
AB  - We examined the relationship between consumption of fruit and vegetables during
      pregnancy and anthropometric measures at birth in a general population mother
      infant cohort in Valencia, Spain. A total of 787 infants born between May 2004
      and February 2006 were included. Fruit and vegetable consumption during pregnancy
      was assessed by a FFQ administered using an in-person interview. We used multiple
      linear regression to assess associations between fruit and vegetable intake (in
      quintiles) and birth weight and length adjusted for sex and gestational age, and
      logistic regression to assess being small for gestational age (SGA) in weight and
      SGA in length, defined as adjusted birth weight or length below the 10th
      percentile. A linear relationship was found between vegetable consumption and
      having a SGA (weight) and SGA (length) baby. Women in the lowest quintile of
      vegetable intake during the first trimester had a higher odds of having a SGA
      (weight) baby than women in the highest quintile [odds ratio (OR), 3.7; 95% CI:
      1.5-8.9; P-trend < 0.001] and had a higher odds of having an SGA (length) baby in
      the third trimester (OR, 5.5; 95% CI: 1.7-17.7; P-trend = 0.04) in multivariate
      analysis. We found a nonmonotonic relationship between adjusted birth weight and
      length and vegetable consumption during the first trimester; newborns in the 2
      lowest quintiles of intake had a significantly lower weight and length than those
      in the 4th quintile. There was no association between fruit consumption and birth
      outcomes. Our findings indicate that vegetable consumption throughout pregnancy
      may have a beneficial effect on fetal growth.

PMID- 19158217
TI  - Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine
      concentrations while minimally affecting the rates of glycine turnover and
      glycine cleavage in healthy men and women.
AB  - Glycine is a precursor of purines, protein, glutathione, and 1-carbon units as
      5,10-methylenetetrahydrofolate. Glycine decarboxylation through the glycine
      cleavage system (GCS) and glycine-serine transformation by serine
      hydroxymethyltransferase (SHMT) require pyridoxal 5'-phosphate (PLP; active form
      of vitamin B-6) as a coenzyme. The intake of vitamin B-6 is frequently low in
      humans. Therefore, we determined the effects of vitamin B-6 restriction on whole
      body glycine flux, the rate of glycine decarboxylation, glycine-to-serine
      conversion, use of glycine carbons in nucleoside synthesis, and other aspects of
      1-carbon metabolism. We used a primed, constant infusion of [1,2-(13)C(2)]glycine
      and [5,5,5-(2)H(3)]leucine to quantify in vivo kinetics in healthy adults (7
      males, 6 females; 20-39 y) of normal vitamin B-6 status or marginal vitamin B-6
      deficiency. Vitamin B-6 restriction lowered the plasma PLP concentration from 55
      +/- 4 nmol/L (mean +/- SEM) to 23 +/- 1 nmol/L (P < 0.0001), which is consistent
      with marginal deficiency, whereas the plasma glycine concentration increased (P <
      0.01). SHMT-mediated conversion of glycine to serine increased from 182 +/- 7 to
      205 +/- 9 micromol x kg(-1) x h(-1) (P < 0.05), but serine production using a GCS
      derived 1-carbon unit (93 +/- 9 vs. 91 +/- 6 micromol x kg(-1) x h(-1)) and
      glycine cleavage (163 +/- 11 vs. 151 +/- 8 micromol x kg(-1) x h(-1)) were not
      changed by vitamin B-6 restriction. The GCS produced 1-carbon units at a rate
      (approximately 140-170 micromol x kg(-1) x h(-1)) that greatly exceeds the demand
      for remethylation and transmethylation processes (approximately 4-7 micromol x
      kg(-1) x h(-1)). We conclude that the in vivo GCS and SHMT reactions are quite
      resilient to the effects of marginal vitamin B-6 deficiency, presumably through a
      compensatory effect of increasing substrate concentration.

PMID- 19158219
TI  - Commentary on domestic animals in agricultural and biomedical research: an
      endangered enterprise.

PMID- 19158220
TI  - Neonatal exposure to daidzein, genistein, or the combination modulates bone
      development in female CD-1 mice.
AB  - Neonatal exposure to genistein (GEN), an isoflavone abundant in soy, favorably
      modulates bone mineral density (BMD) and bone strength in mice at adulthood. The
      study objective was to determine whether early exposure to a combination of the
      soy isoflavones daidzein (DAI) and GEN that naturally exists in soy protein-based
      infant formula results in greater benefits to bone at adulthood than either
      treatment alone. Male and female CD-1 mice (n = 8-16 pups per group per gender)
      were randomized to subcutaneous injections of DAI (2 mg x kg body weight(-1) x d(
      1)), GEN (5 mg x kg body weight(-1) x d(-1)), DAI+GEN (7 mg x kg body weight(-1)
      x d(-1)), diethylstilbesterol (DES; positive control) (2 mg x kg body weight(-1)
      x d(-1)), or control (CON) from postnatal d 1-5 and were studied to 4 mo of age.
      BMD, biomechanical bone strength, and bone microarchitecture were assessed at the
      femur and lumbar vertebrae (LV). Females treated with DAI, GEN, DAI+GEN, or DES
      had greater (P < 0.05) BMD at the LV compared with CON and vertebra in the DAI
      and DES group were more resistant to compression fractures. Microstructural
      analyses demonstrated that treatment with DAI and GEN resulted in greater (P <
      0.05) trabecular connectivity and trabecular thickness, respectively, than the
      CON. In conclusion, neonatal exposure to DAI and/or GEN had a positive effect on
      the skeleton of female mice at adulthood, but, compared with individual
      treatments, DAI+GEN did not have a greater benefit to bone in females or males.

PMID- 19158221
TI  - Direct diet quantification indicates low intakes of (n-3) fatty acids in children
      4 to 8 years old.
AB  - Estimates of essential fatty acid intakes, including (n-3) PUFA, are available in
      pediatric populations based on limited indirect approaches. Furthermore,
      recommended intakes for short- and long-chain (LC) (n-3) PUFA have emerged for
      this population. This study provides direct quantification of fatty acid intakes
      in children aged 4-8 y. Identical portions of all food and natural health
      products consumed over 3 d were collected. Duplicate samples were analyzed for
      energy, macronutrients, and fatty acids, including alpha-linolenic acid (ALA),
      eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic
      acid (DHA) by high performance capillary GLC. The results for 41 children [25
      females, 16 males; 5.8 +/- 0.2 y (mean age +/- SEM)] showed daily energy intakes
      of 5879 +/- 211 kJ (mean +/- SEM) and (n-3) PUFA intakes in mg/d as follows: ALA,
      1161 +/- 108; EPA, 38.4 +/- 9.3; DPA, 26.3 +/- 3.9; and DHA, 54.1 +/- 11.4. Based
      on the Dietary Reference Intakes from the Institute of Medicine, 61% of the
      children met the adequate intake for ALA and 22% met the suggested adequate
      intake for DHA+EPA (10% of the adequate intake for ALA). These intakes were also
      compared with the recent Australia/New Zealand recommendations for children,
      where only 51% met the recommended intake for EPA+DPA+DHA. These results
      demonstrate a moderate shortfall in ALA intake in Canadian children and a
      nutrient gap for the LC (n-3) PUFA, including DHA, when comparing intakes for
      this population to suggested and recommended intakes.

PMID- 19158222
TI  - Dietary patterns predict changes in two-hour post-oral glucose tolerance test
      plasma glucose concentrations in middle-aged adults.
AB  - We examined whether the adherence to major dietary patterns at baseline of 5824
      nondiabetic Danes (30-60 y) enrolled in the nonpharmacological Inter99
      intervention predicted changes in fasting plasma glucose (FPG) and postchallenge
      2-h plasma glucose (2h-PG) concentrations during a 5 y period and whether a
      potential association was dependent on baseline glucose tolerance status. Through
      principal component analysis, a score for a traditional dietary pattern
      (characterized by higher intakes of high-fat sandwich spreads, red meat,
      potatoes, butter and lard, low-fat fish, sandwich meat, and sauces) and a score
      for a modern dietary pattern (characterized by higher intakes of vegetables,
      fruit, vegetable oil/vinegar dressing, poultry, pasta, rice, and cereals) were
      estimated for each person at baseline. Random effect models adjusting for
      relevant confounders were used to estimate changes in repetitive measures of FPG
      and 2h-PG. A higher modern score (of 1 SD) predicted an annual decrease in 2h-PG
      of 0.015 mmol/L (P < 0.01) regardless of glucose tolerance status. For
      individuals with isolated impaired glucose tolerance, a higher traditional score
      (of 1 SD) predicted an annual increase in 2h-PG of 0.083 mmol/L (P < 0.0001). In
      conclusion, glucose tolerance status did not, in general, affect the predictive
      effect of the dietary patterns. The study suggests that the risk of worsening 2h
      PG concentrations may be smaller for individuals with a high modern dietary
      pattern score characterized by high intakes of vegetables, fruit, vegetable
      oil/vinegar dressing, poultry, pasta, rice, and cereals.

PMID- 19158223
TI  - Dairy intake, blood pressure, and incident hypertension in a general Dutch
      population.
AB  - Diet and lifestyle are important for maintaining a healthy blood pressure (BP).
      The role of dairy in the prevention of hypertension, however, is not yet clear.
      We studied the relation of dairy intake with BP in 21,553 Dutch participants aged
      20-65 y who did not use antihypertensive medication. In addition, the risk of
      hypertension was examined in 3454 of these participants with a 5-y follow-up.
      Dairy consumption was assessed at baseline (1993-1997) using a semiquantitative
      FFQ that included 178 foods and beverages. Baseline BP and odds ratios (OR) (95%
      CI) for incident hypertension were calculated in categories of energy-adjusted
      dairy intake with adjustment for age, sex, socioeconomic status, BMI, smoking,
      alcohol use, and dietary intakes. Participants had a median intake of 344 g/d
      (approximately 2.3 servings) for total dairy and 174 g/d (approximately 1.2
      servings) for low-fat dairy. Mean BP was 120/76 mm Hg. Intake of total dairy,
      specific dairy groups (i.e. low-fat, high-fat, fermented) and dairy products
      (i.e. cheese, yogurt) were not consistently related to BP. Of 3454 participants
      who were followed, 713 developed hypertension. The risk of hypertension tended to
      be inversely related to low-fat dairy intake, with multivariate OR (95% CI) of
      1.00, 0.78 (0.61, 1.00), 0.81 (0.63, 1.03), and 0.82 (0.64, 1.06; P-trend: 0.24)
      in consecutive quartiles. We conclude that variations in BP in a general middle
      aged Dutch population cannot be explained by overall dairy intake. A beneficial
      effect of low-fat dairy on risk of hypertension, however, cannot be excluded,
      which warrants further investigation in prospective population-based studies.

PMID- 19158224
TI  - Methodological challenges in the application of the glycemic index in
      epidemiological studies using data from the European Prospective Investigation
      into Cancer and Nutrition.
AB  - Associations between the glycemic index (GI) or glycemic load (GL) and diseases
      are heterogeneous in epidemiological studies. Differences in assigning GI values
      to food items may contribute to this inconsistency. Our objective was to address
      methodological issues related to the use of current GI and GL values in
      epidemiological studies. We performed ecological comparison and correlation
      studies by calculating dietary GI and GL from country-specific dietary
      questionnaires (DQ) from 422,837 participants from 9 countries participating in
      the European Prospective Investigation into Cancer and Nutrition study and single
      standardized 24-h dietary recalls (24-HDR) obtained from a representative sample
      (n = 33,404) using mainly Foster Powell's international table as a reference
      source. Further, 2 inter-rater and 1 inter-method comparison were conducted,
      comparing DQ GI values assigned by independent groups with values linked by us.
      The ecological correlation between DQ and 24-HDR was good for GL (overall r =
      0.76; P < 0.005) and moderate for GI (r = 0.57; P < 0.05). Mean GI/GL differences
      between DQ and 24-HDR were significant for most centers. GL but not GI from DQ
      was highly correlated with total carbohydrate (r = 0.98 and 0.15, respectively; P
      < 0.0001) and this was higher for starch (r = 0.72; P < 0.0001) than for sugars
      (r = 0.36; P < 0.0001). The inter-rater and inter-method variations were
      considerable for GI (weighted kappa coefficients of 0.49 and 0.65 for inter-rater
      and 0.25 for inter-method variation, respectively) but only mild for GL (weighted
      kappa coefficients > 0.80). A more consistent methodology to attribute GI values
      to foods and validated DQ is needed to derive meaningful GI/GL estimates for
      nutritional epidemiology.

PMID- 19158225
TI  - DHA supplementation decreases serum C-reactive protein and other markers of
      inflammation in hypertriglyceridemic men.
AB  - Dietary (n-3) PUFA reduce inflammation, an independent risk factor for
      cardiovascular disease. The antiinflammatory effects of docosahexaenoic acid
      (DHA) in hypertriglyceridemic men have not been previously reported, to our
      knowledge, and were the focus of this study. Hypertriglyceridemic men (n = 17 per
      group) aged 39-66 y, participated in a double-blind, randomized, placebo
      controlled parallel study. They received no supplements for the first 8 d and
      then received either 7.5 g/d DHA oil (3 g DHA/d) or olive oil (placebo) for the
      last 90 d. Blood samples were collected from fasting men on study days -7, 0, 45,
      84, and 91. DHA supplementation for 45 and 91 d decreased the number of
      circulating neutrophils by 11.7 and 10.5%, respectively (P < 0.05). It did not
      alter the circulating concentrations of other inflammatory markers tested within
      45 d, but at 91 d it reduced (P < 0.05) concentrations of C-reactive protein
      (CRP) by 15%, interleukin-6 by 23%, and granulocyte monocyte-colony stimulating
      factor by 21% and DHA increased the concentration of antiinflammatory matrix
      metalloproteinase-2 by 7%. The number of circulating neutrophils was positively
      associated with the weight percent (wt %) of 20:4(n-6) in RBC lipids, and
      negatively to the wt % of 20:5(n-3) and 22:6(n-3). Concentrations of CRP and
      serum amyloid A were positively associated with the sum of SFA and negatively
      with the wt % of 18:1(n-9) and 17:0 in RBC lipids; CRP was also positively
      associated with the wt % of 20:2(n-6). The mean size of VLDL particles was
      positively associated with plasma concentrations of neutrophils and CRP. In
      conclusion, DHA may lessen the inflammatory response by altering blood lipids and
      their fatty acid composition.

PMID- 19158226
TI  - Supplements of 20 microg/d cholecalciferol optimized serum 25-hydroxyvitamin D
      concentrations in 80% of premenopausal women in winter.
AB  - The serum 25-hydroxyvitamin D [25(OH)D] response to daily supplementation with 20
      microg cholecalciferol (D3) during winter in predominantly white premenopausal
      women living in Maine was measured and the effects of body composition and
      hormonal contraceptive use on baseline serum 25(OH)D concentrations and the
      response to supplementation were examined. A total of 112 women (22.2 +/- 3.7 y
      old) received placebo from March 2005 until September 2005 when they were
      randomized to receive either placebo or 20 microg/d D3 through February 2006.
      Eighty-six women completed the study. Actual mean D3 content of the supplements
      was 22 microg per capsule. In February 2005 the serum 25(OH)D concentration was
      62.0 +/- 23.4 nmol/L (mean +/- SD). Serum 25(OH)D concentrations increased by
      35.3 +/- 23.2 nmol/L from February 2005 to February 2006 in the treatment group,
      significantly more than the 10.9 +/- 16.9 nmol/L increase in the placebo group.
      Treatment group, magnitude of summer increase in 25(OH)D, estrogen dose, and
      baseline serum 25(OH)D concentrations, but not body fat, were significant
      predictors of the 1-y change in 25(OH)D concentrations used to assess the
      magnitude of the response to supplementation. Daily supplementation with 20
      microg D3 during winter achieved optimal 25(OH)D concentrations (> or = 75
      nmol/L) in 80% of participants, indicating that this dose is adequate to optimize
      vitamin D status in most young women in Maine.

PMID- 19158227
TI  - Energy intake of Swedish overweight and obese children is underestimated using a
      diet history interview.
AB  - Estimating energy intake (EI) of a child by using a diet history interview (DHI)
      method may be a challenge because of difficulty for the child to remember what
      has been eaten as well as to report portion sizes. The aim of this research was
      to validate reported EI from a DHI in children classified as overweight or obese
      by comparing the reported EI to total energy expenditure (TEE) measured by 2
      objective measures. Eighty-five 10.5- +/- 1.1-y-old overweight and obese
      children, with help from 1 or 2 parents, reported their EI 2 wk retrospectively
      in a DHI. Reported EI was compared with TEE, as measured by SenseWear armband (n
      = 85) and the doubly-labeled water (DLW) method (n = 21), during the same period
      as the DHI. Reported EI was underestimated by 14% when validated against both the
      armband and DLW method. Underestimation did not differ between boys and girls.
      However, the EI of obese children was underestimated by 22%, which is twice the
      rate as for the overweight children (95% CI: 0.55, 3.08). Underestimated EI was
      negatively correlated with BMI (r = -0.38; P = <0.01) as well as age (r = -0.21;
      P = 0.05). EI is underestimated to a higher extent among children with higher BMI
      and higher age when using a DHI method. The findings show the importance of
      validating dietary intake of children in general and in overweight and obese
      children in particular.

PMID- 19158228
TI  - A moderate-protein diet produces sustained weight loss and long-term changes in
      body composition and blood lipids in obese adults.
AB  - Diets with increased protein and reduced carbohydrates (PRO) are effective for
      weight loss, but the long-term effect on maintenance is unknown. This study
      compared changes in body weight and composition and blood lipids after short-term
      weight loss (4 mo) followed by weight maintenance (8 mo) using moderate PRO or
      conventional high-carbohydrate (CHO) diets. Participants (age = 45.4 +/- 1.2 y;
      BMI = 32.6 +/- 0.8 kg/m(2); n = 130) were randomized to 2 energy-restricted diets
      (-500 kcal/d or -2093 kJ/d): PRO with 1.6 g x kg(-1) x d(-1) protein and <170 g/d
      carbohydrates or CHO with 0.8 g x kg(-1) x d(-1) protein, >220 g/d carbohydrates.
      At 4 mo, the PRO group had lost 22% more fat mass (FM) (-5.6 +/- 0.4 kg) than the
      CHO group (-4.6 +/- 0.3 kg) but weight loss did not differ between groups (-8.2
      +/- 0.5 kg vs. -7.0 +/- 0.5 kg; P = 0.10). At 12 mo, the PRO group had more
      participants complete the study (64 vs. 45%, P < 0.05) with greater improvement
      in body composition; however, weight loss did not differ between groups (-10.4 +/
      1.2 kg vs. -8.4 +/- 0.9 kg; P = 0.18). Using a compliance criterion of
      participants attaining >10% weight loss, the PRO group had more participants (31
      vs. 21%) lose more weight (-16.5 +/- 1.5 vs. -12.3 +/- 0.9 kg; P < 0.01) and FM (
      11.7 +/- 1.0 vs. -7.9 +/- 0.7 kg; P < 0.01) than the CHO group. The CHO diet
      reduced serum cholesterol and LDL cholesterol compared with PRO (P < 0.01) at 4
      mo, but the effect did not remain at 12 mo. PRO had sustained favorable effects
      on serum triacylglycerol (TAG), HDL cholesterol (HDL-C), and TAG:HDL-C compared
      with CHO at 4 and 12 mo (P < 0.01). The PRO diet was more effective for FM loss
      and body composition improvement during initial weight loss and long-term
      maintenance and produced sustained reductions in TAG and increases in HDL-C
      compared with the CHO diet.

PMID- 19158229
TI  - Zinc deficiency is common among healthy women of reproductive age in Bhaktapur,
      Nepal.
AB  - Zinc deficiency is a major public health problem in many developing countries.
      However, its prevalence is still unknown in most populations. Women of
      reproductive age in developing countries are highly vulnerable to nutritional
      deficiencies, including that of zinc. To estimate the prevalence of zinc
      deficiency and to identify important dietary sources of zinc, we undertook a
      cross-sectional survey in 500 nonpregnant Nepalese women and measured their
      plasma zinc concentrations. We also examined the associations between plasma zinc
      and dietary intake of zinc or phytate, iron status, plasma concentrations of C
      reactive protein, albumin, and hemoglobin. Food intake was estimated by 2 24-h
      dietary recalls and 1 FFQ for each woman. The plasma zinc concentration was (mean
      +/- SD) 8.5 +/- 2.4 micromol/L and more than three-quarters of the women were
      zinc deficient. Dietary zinc intake did not predict plasma zinc concentration,
      whereas phytate intake was negatively and significantly associated with plasma
      zinc. The other variables that were associated with plasma zinc were plasma
      albumin and hemoglobin concentration. Rice contributed 50% to the total estimated
      daily zinc intake and wheat and meat each contributed 15%. Rice also contributed
      68% to the daily intake of phytate. In conclusion, we found that zinc deficiency
      was common in women of reproductive age and that the foods contributing
      substantial amounts of zinc also contributed importantly to the intake of
      phytate.

PMID- 19158230
TI  - Increasing total fiber intake reduces risk of weight and fat gains in women.
AB  - Research investigating fiber intake and changes in weight over time has not
      controlled for important covariates, especially physical activity. Moreover,
      studies have rarely examined the influence of fiber on changes in body fat, only
      weight. Hence, this study was conducted to determine whether changes in fiber
      intake (total, soluble, and insoluble) influence risk of gaining weight and body
      fat over time. Another objective was to examine the influence of age, energy
      intake, activity, season, and other potential confounders. A prospective cohort
      design was used and 252 women completed baseline and follow-up assessments 20 mo
      apart. Diet was measured using 7-d weighed food records. Fiber was expressed per
      1000 kcal (4187 kJ). Body fat was assessed via the Bod Pod and physical activity
      was measured using accelerometers over 7 consecutive days. Across the 20 mo,
      almost 50% of the women gained weight and fat. For each 1 g increase in total
      fiber consumed, weight decreased by 0.25 kg (P = 0.0061) and fat decreased by
      0.25 percentage point (P = 0.0052). Controlling for potential confounders did not
      affect the relationships, except changes in energy intake, which weakened the
      associations by 24-32%. Soluble and insoluble fibers were borderline predictors
      of changes in weight and fat. In conclusion, increasing dietary fiber
      significantly reduces the risk of gaining weight and fat in women, independent of
      several potential confounders, including physical activity, dietary fat intake,
      and others. Fiber's influence seems to occur primarily through reducing energy
      intake over time.

PMID- 19158231
TI  - Orally administered zinc increases food intake via vagal stimulation in rats.
AB  - We investigated the role of zinc in food intake regulation using rats during
      early-stage zinc deficiency without decreased zinc concentrations in plasma and
      tissues. Plasma, liver, and hypothalamic zinc concentrations were not affected in
      male Sprague-Dawley rats fed a zinc-deficient (Zn-Def) diet for 3 d compared with
      the pair-fed control group, which was fed a zinc-sufficient diet to the intake of
      the Zn-Def diet. Zinc sulfate at a dose of 19 micromol/kg body weight was orally
      or intraperitoneally (i.p.) administered to rats fed a Zn-Def diet for 3d and
      food intake was measured. We found that zinc stimulated food intake after oral
      but not i.p. administration. The mRNA expression of neuropeptide Y (NPY) and
      orexin in the hypothalamus significantly increased 3 h after oral but not i.p.
      administration of zinc. Pretreatment with an antagonist for the NPY Y(1) receptor
      or the orexin OX(1) receptor blocked orexigenic activity after oral
      administration of zinc. The stimulation of food intake by oral administration of
      zinc was abolished by vagotomy. Taken together, orally administered zinc may
      stimulate food intake via orexigenic peptides coupled to the afferent vagal
      stimulation in rats after short-term treatment with a Zn-Def diet.

PMID- 19158232
TI  - Histology does not influence prognosis in differentiated thyroid carcinoma when
      accounting for age, tumour diameter, invasive growth and metastases.
AB  - OBJECTIVE: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma
      (FTC) show considerable differences in disease stage at initial presentation. The
      aim of this study was to investigate whether there are differences in tumour
      specific survival if initial staging is accounted for. DESIGN: Retrospective
      chart review study. PATIENTS: The study sample comprised 875 PTC and 350 FTC
      patients (856 females, 369 males, mean age 47.8 years) treated in our hospital
      from 1978 to 2002. All patients received total thyroidectomy with subsequent I
      131 ablation except for those patients with an isolated papillary microcarcinoma.
      METHODS: Kaplan-Meier analyses and Cox-regression analyses were performed to
      assess the influence of histology on thyroid cancer-specific survival. RESULTS:
      FTC patients were on average older, more likely to be male, presented with a
      larger tumour and more frequently had multifocal carcinoma and distant metastases
      than PTC patients, whereas they presented less frequently with extrathyroidal
      invasion or lymph node metastases. Twenty-year tumour-specific survival in PTC
      was 90.6% and in FTC 73.7% (P<0.001). In multivariate analysis the presence of
      distant metastases (P<0.001), age (P<0.001), tumour size (P=0.001) and the
      presence of extrathyroidal invasion (P=0.007), but not histology (P=0.26), were
      independent determinant variables for tumour-specific survival. CONCLUSION: There
      is no difference in tumour-specific survival between PTC and FTC when accounting
      for the presence of metastases, age, tumour size and the presence of
      extrathyroidal invasion.

PMID- 19158233
TI  - Corticosteroid receptors, macrophages and cardiovascular disease.
AB  - The mineralocorticoid receptor (MR) and glucocorticoid receptor are ligand
      activated transcription factors that have important physiological and
      pathophysiological actions in a broad range of cell types including monocytes and
      macrophages. While the glucocorticoids cortisol and corticosterone have well
      described anti-inflammatory actions on both recruited and tissue resident
      macrophages, a role for the mineralocorticoid aldosterone in these cells is
      largely undefined. Emerging evidence, however, suggests that MR signalling may
      promote pro-inflammatory effects. This review will discuss the current
      understanding of the role of corticosteroid receptors in macrophages and their
      effect on diseases involving inflammation, with a particular focus on
      cardiovascular disease.

PMID- 19158234
TI  - Role of angiotensin II-induced rapid response genes in the regulation of enzymes
      needed for aldosterone synthesis.
AB  - Aldosterone is principally synthesized in the zona glomerulosa of the adrenal by
      a series of enzymatic reactions leading to the conversion of cholesterol to
      aldosterone. Angiotensin II (Ang II) is the major physiological regulator of
      aldosterone production acting acutely to stimulate aldosterone biosynthesis and
      chronically to increase the capacity of the adrenals to produce aldosterone. We
      previously defined eight transcription factors that are rapidly induced following
      Ang II treatment using three in vitro adrenocortical cell models. Herein, we
      investigated the function of these transcription factors in the regulation of the
      enzymes needed for aldosterone production. H295R adrenal cells were co
      transfected with expression vectors for each transcription factor and
      promoter/reporter constructs prepared for genes encoding the enzymes needed for
      aldosterone production. NGFI-B family members induced promoter activity of 3-beta
      hydroxysteroid-dehydrogenase type 2 (HSD3B2), 21-hydroxylase (CYP21A2), and
      aldosterone synthase (CYP11B2). The importance of NGFI-B in the regulation of
      CYP11B2 was also demonstrated by reduced CYP11B2 transcription in the presence of
      a dominant-negative-NGFI-B. A pharmacological approach was used to characterize
      the Ang II pathways regulating transcription of NGFI-B family genes.
      Transcription of NGFI-B members were decreased following inhibition of Ang II
      type 1 receptor (AT1R), protein kinase C (PKC), calcium/calmodulin-dependent
      kinases (CaMK), and Src tyrosine kinase (SRC). Taken together, these results
      suggest that Ang II binding to the AT1R increases activity of PKC, CaMK, and SRC,
      which act to increase expression of the family of NGFI-B genes as well as
      CYP11B2. Ang II induction of the NGFI-B family members represents an important
      pathway to increase the capacity of adrenal cells to produce aldosterone.

PMID- 19158236
TI  - Managing grief and relationship roles influence which forms of social support the
      bereaved needs.
AB  - Social support is important during the bereavement period and influences which
      form of social support the grieving person needs. This study shows 2 different
      strategies for coping with grief which also revealed which form of social support
      the grieving persons needed depend on what they found difficult to manage. The
      coping strategies are called grief management and involve different strategies
      and the roles in the relationship with the diseased. Systematically monitoring
      the bereaved makes it possible to understand the strategies they use in the
      grieving process and to identify when these strategies are insufficient so
      professional support can be offered.

PMID- 19158235
TI  - Cervix remodeling and parturition in the rat: lack of a role for hypogastric
      innervation.
AB  - The hypogastric nerve is a major pathway innervating the uterine cervix, yet its
      contribution to the processes of cervical ripening and parturition is not known.
      The main objective of this study was to determine the effect of hypogastric nerve
      transection on remodeling of the cervix and timing of birth. As an initial goal,
      processes associated with remodeling of the peripartum cervix were studied. The
      cervix was obtained from time-dated pregnant rats on days 15, 19, 21, and 21.5 of
      pregnancy, and post partum on the day of birth (day 22). The cervix was excised,
      post-fixed overnight, and sections stained to evaluate collagen content and
      structure or processed by immunohistochemistry to identify macrophages or nerve
      fibers. The census of macrophages and density of nerve fibers in the cervix
      peaked on day 21, the day before birth, and then declined post partum. These
      results replicate in time course and magnitude previous studies in mice. To
      address the main objective, the hypogastric nerve was bilaterally transected on
      day 15 post-breeding; sham-operated rats served as controls. Pups were born in
      both groups at normal term. Transection of the hypogastric nerves did not affect
      remodeling of collagen or the census of macrophages or the density of nerve
      fibers in the cervix. These findings support the contention that enhanced
      innervation and immigration of immune cells are associated with remodeling of the
      cervix and parturition, but that a neural pathway other than the hypogastric
      nerve may participate in the process of cervical ripening.

PMID- 19158237
TI  - Process evaluation of the Hunter Illawarra Kids Challenge Using Parent Support
      study: a multisite randomized controlled trial for the management of child
      obesity.
AB  - The purposes of this article are to (a) outline findings from secondary or
      process outcome data of the Hunter Illawarra Kids Challenge Using Parent Support
      (HIKCUPS) study and (b) inform the design and development of future research
      interventions and practice in the management of child obesity. Data were
      collected by means of facilitator evaluations, independent session observation,
      attendance records, and parent questionnaires. Internal validity and reliability
      of the program delivery were high. All parents reported positive changes in their
      children as a result of the physical activity program, the dietary modification
      program, or both. Most participants completed the home activities, but more than
      half reported that finding time to do them was problematic. Facilitator review
      indicated that future programs should specifically cater to children of similar
      age or same sex, allow adequate time for explanation of complex nutritional
      concepts, and use intrinsic motivators for participants. Recommendations for
      future interventions, specifically the implementation of subsequent HIKCUPS or
      other multisite effectiveness studies, are detailed.

PMID- 19158238
TI  - Demonstration of sustained drug-resistant human immunodeficiency virus type 1
      lineages circulating among treatment-naive individuals.
AB  - Transmission of human immunodeficiency virus (HIV) drug resistance is well
      recognized and compromises response to first-line therapy. However, the
      population dynamics of transmitted resistance remains unclear, although previous
      models have assumed that such transmission reflects direct infection from treated
      individuals. We investigated whether population-based phylogenetic analyses would
      uncover lineages of resistant viruses circulating in untreated individuals.
      Through the phylogenetic analysis of 14,061 HIV type 1 (HIV-1) pol gene sequences
      generated in the United Kingdom from both treatment-naive and -experienced
      individuals, we identified five treatment-independent viral clusters containing
      mutations conferring cross-resistance to antiretroviral drugs prescribed today in
      the United Kingdom. These viral lineages represent sustainable reservoirs of
      resistance among new HIV infections, independent of treatment. Dated phylogenies
      reconstructed through Bayesian Markov chain Monte Carlo inference indicated that
      these reservoirs originated between 1997 and 2003 and have persisted in the HIV
      infected population for up to 8 years. Since our cohort does not represent all
      infected individuals within the United Kingdom, our results are likely to
      underestimate the number and size of the resistant reservoirs circulating among
      drug-naive patients. The existence of sustained reservoirs of resistance in the
      absence of treatment has the capacity to threaten the long-term efficacy of
      antiretroviral therapy and suggests there is a limit to the decline of
      transmitted drug resistance. Given the current decrease in resistance transmitted
      from treated individuals, a greater proportion of resistance is likely to come
      from drug-naive lineages. These findings provide new insights for the planning
      and management of treatment programs in resource-rich and developing countries.

PMID- 19158239
TI  - Robust in vivo transduction of a genetically stable Epstein-Barr virus episome to
      hepatocytes in mice by a hybrid viral vector.
AB  - To make a safe, long-lasting gene delivery vehicle, we developed a hybrid vector
      that leverages the relative strengths of adenovirus and Epstein-Barr virus (EBV).
      A fully gene-deleted helper-dependent adenovirus (HDAd) is used as the delivery
      vehicle for its scalability and high transduction efficiency. Upon delivery, a
      portion of the HDAd vector is recombined to form a circular plasmid. This episome
      includes two elements from EBV: an EBV nuclear antigen 1 (EBNA1) expression
      cassette and an EBNA1 binding region. Along with a human replication origin,
      these elements provide considerable genetic stability to the episome in
      replicating cells while avoiding insertional mutagenesis. Here, we demonstrate
      that this hybrid approach is highly efficient at delivering EBV episomes to
      target cells in vivo. We achieved nearly 100% transduction of hepatocytes after a
      single intravenous injection in mice. This is a substantial improvement over the
      transduction efficiency of previously available physical and viral methods.
      Bioluminescent imaging of vector-transduced mice demonstrated that luciferase
      transgene expression from the hybrid was robust and compared well to a
      traditional HDAd vector. Quantitative PCR analysis confirmed that the EBV episome
      was stable at approximately 30 copies per cell for up to 50 weeks and that it
      remained circular and extrachromosomal. Approaches for adapting the HDAd-EBV
      hybrid to a variety of disease targets and the potential benefits of this
      approach are discussed.

PMID- 19158240
TI  - Oncostatin M enhances the antiviral effects of type I interferon and activates
      immunostimulatory functions in liver epithelial cells.
AB  - Oncostatin M (OSM) is released together with type I interferon (IFN) by activated
      dendritic cells, suggesting a concerted action of these cytokines in the
      biological response against infection. We found that OSM increases the antiviral
      effect of IFN-alpha in Huh7 hepatoma cells infected with hepatitis A or hepatitis
      C virus and synergizes with IFN-alpha in the induction of antiviral genes. The
      combination of OSM and IFN-alpha led to upregulation of both STAT1 and STAT3
      together with intense and prolonged activation of STAT1, STAT3, and Jak1. OSM
      with or without IFN-alpha also activated p38 mitogen-activated protein kinase,
      which is known to enhance transcription of IFN-alpha-inducible genes.
      Interestingly, OSM combined with IFN-alpha strongly induced immunoproteasome
      genes and other genes involved in antigen processing and presentation. Moreover,
      OSM, alone or in combination with IFN-alpha, upregulated relevant innate immunity
      molecules and increased the expression of intracellular adhesion molecule 1 and
      interleukin-15 receptor alpha (IL-15Ralpha) in liver cells. Hepatoma cells
      transfected with a plasmid encoding a viral antigen were able to activate
      effector T cells when pretreated with IFN-alpha plus OSM but not with each
      cytokine separately. Also, OSM, more than IFN-alpha, augmented the ability of
      Huh7 cells to transpresent IL-15 to responding lymphocytes and increased the
      immunostimulatory activity of liver epithelial cells by presenting a short viral
      peptide to sensitized cytotoxic T cells. In conclusion, OSM enhances the
      antiviral effects of type I interferon and cooperates with it in the induction of
      adaptive immune responses to pathogens. These findings may have therapeutic
      implications.

PMID- 19158241
TI  - Herpesvirus gB-induced fusion between the virion envelope and outer nuclear
      membrane during virus egress is regulated by the viral US3 kinase.
AB  - Herpesvirus capsids collect along the inner surface of the nuclear envelope and
      bud into the perinuclear space. Enveloped virions then fuse with the outer
      nuclear membrane (NM). We previously showed that herpes simplex virus (HSV)
      glycoproteins gB and gH act in a redundant fashion to promote fusion between the
      virion envelope and the outer NM. HSV mutants lacking both gB and gH accumulate
      enveloped virions in herniations, vesicles that bulge into the nucleoplasm.
      Earlier studies had shown that HSV mutants lacking the viral serine/threonine
      kinase US3 also accumulate herniations. Here, we demonstrate that HSV gB is
      phosphorylated in a US3-dependent manner in HSV-infected cells, especially in a
      crude nuclear fraction. Moreover, US3 directly phosphorylated the gB cytoplasmic
      (CT) domain in in vitro assays. Deletion of gB in the context of a US3-null virus
      did not add substantially to defects in nuclear egress. The majority of the US3
      dependent phosphorylation of gB involved the CT domain and amino acid T887, a
      residue present in a motif similar to that recognized by US3 in other proteins.
      HSV recombinants lacking gH and expressing either gB substitution mutation T887A
      or a gB truncated at residue 886 displayed substantial defects in nuclear egress.
      We concluded that phosphorylation of the gB CT domain is important for gB
      mediated fusion with the outer NM. This suggested a model in which the US3 kinase
      is incorporated into the tegument layer (between the capsid and envelope) in HSV
      virions present in the perinuclear space. By this packaging, US3 might be brought
      close to the gB CT tail, leading to phosphorylation and triggering fusion between
      the virion envelope and the outer NM.

PMID- 19158242
TI  - Olfactory system involvement in natural scrapie disease.
AB  - The olfactory system (OS) is involved in many infectious and neurodegenerative
      diseases, both human and animal, and it has recently been investigated in regard
      to transmissible spongiform encephalopathies. Previous assessments of nasal
      mucosa infection by prions following intracerebral challenge suggested a
      potential centrifugal spread along the olfactory nerve fibers of the pathological
      prion protein (PrP(Sc)). Whether the nasal cavity may be a route for centripetal
      prion infection to the brain has also been experimentally studied. With the
      present study, we wanted to determine whether prion deposition in the OS occurs
      also under field conditions and what type of anatomical localization PrP(Sc)
      might display there. We report here on detection by different techniques of
      PrP(Sc) in the nasal mucosa and in the OS-related brain areas of sheep affected
      by natural scrapie. PrP(Sc) was detected in the perineurium of the olfactory
      nerve bundles in the medial nasal concha and in nasal-associated lymphoid tissue.
      Olfactory receptor neurons did not show PrP(Sc) immunostaining. PrP(Sc)
      deposition was found in the brain areas of olfactory fiber projection, chiefly in
      the olfactory bulb and the olfactory cortex. The prevalent PrP(Sc) deposition
      patterns were subependymal, perivascular, and submeningeal. This finding,
      together with the discovery of an intense PrP(Sc) immunostaining in the meningeal
      layer of the olfactory nerve perineurium, at the border with the subdural space
      extension surrounding the nerve rootlets, strongly suggests a probable role of
      cerebrospinal fluid in conveying prion infectivity to the nasal submucosa.

PMID- 19158243
TI  - Site of human rhinovirus RNA uncoating revealed by fluorescent in situ
      hybridization.
AB  - By using fluorescent in situ hybridization (FISH), we visualized viral RNA of
      human rhinovirus type 2 (HRV2) during its entry into HeLa cells. RNA uncoating of
      HRV2 is entirely dependent on low endosomal pH (< or =5.6). When internalized
      into cells treated with bafilomycin, which results in neutralization of the
      endosomal pH, no FISH signal was recorded, whereas in the absence of the drug,
      fluorescent dots were seen. Therefore, FISH detects the genomic viral RNA only
      upon its release from the capsid. Free viral RNA was first seen at 10 min
      postinfection (p.i.) in the perinuclear area of the cell, which is indicative of
      RNA release in/from late endosomal compartments. Pulse-chase experiments and
      observation of HRV2 RNA and capsid proteins via microscopy, Western blotting, and
      reverse transcription-PCR revealed that the RNA signal persisted whereas the
      protein signal disappeared. This demonstrates transport of capsids to lysosomes
      and degradation. In contrast, viral RNA that had already been transferred into
      the cytoplasm escaped lysosomal breakdown as indicated by a persistent FISH
      signal. Taken together, our results demonstrate by direct means RNA arrival in
      the cytosol within 10 min p.i. Based on persistence of the FISH signal and
      productive infection in the presence of the microtubule-depolymerizing drug
      nocodazole, we localized this process to endosomal carrier vesicles/late
      endosomes.

PMID- 19158244
TI  - Peptidylproline cis-trans-isomerase Pin1 interacts with human T-cell leukemia
      virus type 1 tax and modulates its activation of NF-kappaB.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus
      etiologically causal of adult T-cell leukemia (ATL). The virus encodes a Tax
      oncoprotein that functions in transcriptional regulation, cell cycle control, and
      transformation. ATL is a highly virulent cancer that is resistant to
      chemotherapeutic treatments. To understand this disease better, it is important
      to comprehend how HTLV-1 promotes cellular growth and survival. Tax activation of
      NF-kappaB is important for the proliferation and transformation of virus-infected
      cells. We show here that prolyl isomerase Pin1 is over expressed in HTLV-1 cell
      lines; Pin1 binds Tax and regulates Tax-induced NF-kappaB activation.

PMID- 19158245
TI  - Nucleotide sequence requirements at the 5' end of the influenza A virus M RNA
      segment for efficient virus replication.
AB  - The mechanism by which the influenza A virus genome is packaged into virions is
      not fully understood. The coding and noncoding regions necessary for packaging of
      the viral RNA segments, except for the M segment, have been identified. Here, we
      delineate the M segment regions by incorporating a reporter viral RNA into
      virions and by generating viruses possessing mutations in the regions. We found
      that, like the other segments, the M segment coding regions are essential for
      virion incorporation and that the nucleotide length rather than the nucleotide
      sequence of the 5' end of the coding region is important.

PMID- 19158246
TI  - Proteolytic activation of the 1918 influenza virus hemagglutinin.
AB  - Proteolytic activation of the hemagglutinin (HA) protein is indispensable for
      influenza virus infectivity, and the tissue expression of the responsible
      cellular proteases impacts viral tropism and pathogenicity. The HA protein
      critically contributes to the exceptionally high pathogenicity of the 1918
      influenza virus, but the mechanisms underlying cleavage activation of the 1918 HA
      have not been characterized. The neuraminidase (NA) protein of the 1918 influenza
      virus allows trypsin-independent growth in canine kidney cells (MDCK). However,
      it is at present unknown if the 1918 NA, like the NA of the closely related
      strain A/WSN/33, facilitates HA cleavage activation by recruiting the proprotease
      plasminogen. Moreover, it is not known which pulmonary proteases activate the
      1918 HA. We provide evidence that NA-dependent, trypsin-independent cleavage
      activation of the 1918 HA is cell line dependent and most likely plasminogen
      independent since the 1918 NA failed to recruit plasminogen and neither exogenous
      plasminogen nor the presence of the A/WSN/33 NA promoted efficient cleavage of
      the 1918 HA. The transmembrane serine protease TMPRSS4 was found to be expressed
      in lung tissue and was shown to cleave the 1918 HA. Accordingly, coexpression of
      the 1918 HA with TMPRSS4 or the previously identified HA-processing protease
      TMPRSS2 allowed trypsin-independent infection by pseudotypes bearing the 1918 HA,
      indicating that these proteases might support 1918 influenza virus spread in the
      lung. In summary, we show that the previously reported 1918 NA-dependent spread
      of the 1918 influenza virus is a cell line-dependent phenomenon and is not due to
      plasminogen recruitment by the 1918 NA. Moreover, we provide evidence that
      TMPRSS2 and TMPRSS4 activate the 1918 HA by cleavage and therefore may promote
      viral spread in lung tissue.

PMID- 19158247
TI  - Self-assembly of Epstein-Barr virus capsids.
AB  - Epstein-Barr virus (EBV), a member of the Gammaherpesvirus family, primarily
      infects B lymphocytes and is responsible for a number of lymphoproliferative
      diseases. The molecular genetics of the assembly pathway and high-resolution
      structural analysis of the capsid have not been determined for this
      lymphocryptovirus. As a first step in studying EBV capsid assembly, the
      baculovirus expression vector (BEV) system was used to express the capsid shell
      proteins BcLF1 (major capsid protein), BORF1 (triplex protein), BDLF1 (triplex
      protein), and BFRF3 (small capsid protein); the internal scaffold protein, BdRF1;
      and the maturational protease (BVRF2). Coinfection of insect cells with the six
      viruses expressing these proteins resulted in the production of closed capsid
      structures as judged by electron microscopy and sedimentation methods. Therefore,
      as shown for other herpesviruses, only six proteins are required for EBV capsid
      assembly. Furthermore, the small capsid protein of EBV (BFRF3), like that of
      Kaposi's sarcoma-associated herpesvirus, was found to be required for assembly of
      a stable structure. Localization of the small capsid protein to nuclear assembly
      sites required both the major capsid (BcLF1) and scaffold proteins (BdRF1) but
      not the triplex proteins. Mutational analysis of BFRF3 showed that the N-terminal
      half (amino acids 1 to 88) of this polypeptide is required and sufficient for
      capsid assembly. A region spanning amino acids 65 to 88 is required for the
      concentration of BFRF3 at a subnuclear site and the N-terminal 65 amino acids
      contain the sequences required for interaction with major capsid protein. These
      studies have identified the multifunctional role of the gammaherpesvirus small
      capsid proteins.

PMID- 19158248
TI  - Differential neutralization of human immunodeficiency virus (HIV) replication in
      autologous CD4 T cells by HIV-specific cytotoxic T lymphocytes.
AB  - Defining the antiviral efficacy of CD8 T cells is important for immunogen design,
      and yet most current assays do not measure the ability of responses to neutralize
      infectious virus. Here we show that human immunodeficiency virus (HIV)-specific
      cytotoxic T-lymphocyte (CTL) clones and cell lines derived from infected persons
      and targeting diverse epitopes differ by over 1,000-fold in their ability to
      retard infectious virus replication in autologous CD4 T cells during a 7-day
      period in vitro, despite comparable activity as assessed by gamma interferon (IFN
      gamma) enzyme-linked immunospot (ELISPOT) assay. Cell lines derived from
      peripheral blood mononuclear cells stimulated in vitro with peptides representing
      targeted Gag epitopes consistently neutralized HIV better than Env-specific lines
      from the same person, although ineffective inhibition of virus replication is not
      a universal characteristic of Env-specific responses at the clonal level. Gag
      specific cell lines were of higher avidity than Env-specific lines, although
      avidity did not correlate with the ability of Gag- or Env-specific lines to
      contain HIV replication. The greatest inhibition was observed with cell lines
      restricted by the protective HLA alleles B*27 and B*57, but stimulation with
      targeted Gag epitopes resulted in greater inhibition than did stimulation with
      targeted Env epitopes even in non-B*27/B*57 subjects. These results assessing
      functional virus neutralization by HIV-specific CD8 T cells indicate that there
      are marked epitope- and allele-specific differences in virus neutralization by in
      vitro-expanded CD8 T cells, a finding not revealed by standard IFN-gamma ELISPOT
      assay currently in use in vaccine trials, which may be of critical importance in
      immunogen design and testing of candidate AIDS vaccines.

PMID- 19158249
TI  - Coagulation factors IX and X enhance binding and infection of adenovirus types 5
      and 31 in human epithelial cells.
AB  - Most adenoviruses bind directly to the coxsackie and adenovirus receptor (CAR) on
      target cells in vitro, but recent research has shown that adenoviruses can also
      use soluble components in body fluids for indirect binding to target cells. These
      mechanisms have been identified upon addressing the questions of how to de- and
      retarget adenovirus-based vectors for human gene and cancer therapy, but the
      newly identified mechanisms also suggest that the role of body fluids and their
      components may also be of importance for natural, primary infections. Here we
      demonstrate that plasma, saliva, and tear fluid promote binding and infection of
      adenovirus type 5 (Ad5) in respiratory and ocular epithelial cells, which
      corresponds to the natural tropism of most adenoviruses, and that plasma promotes
      infection by Ad31. By using a set of binding and infection experiments, we also
      found that Ad5 and Ad31 require coagulation factors IX (FIX) or X (FX) or just
      FIX, respectively, for efficient binding and infection. The concentrations of
      these factors that were required for maximum binding were 1/100th of the
      physiological concentrations. Preincubation of virions with heparin or
      pretreatment of cells with heparinase I indicated that the role of cell surface
      heparan sulfate during FIX- and FX-mediated adenovirus binding and infection is
      mechanistically serotype specific. We conclude that the use of coagulation
      factors by adenoviruses may be of importance not only for the liver tropism seen
      when administering adenovirus vectors to the circulation but also during primary
      infections by wild-type viruses of their natural target cell types.

PMID- 19158250
TI  - Poxvirus MC160 protein utilizes multiple mechanisms to inhibit NF-kappaB
      activation mediated via components of the tumor necrosis factor receptor 1 signal
      transduction pathway.
AB  - Poxviruses express proteins that limit host immune responses to infection. For
      example, the molluscum contagiosum virus MC160 protein inhibits tumor necrosis
      factor alpha (TNF-alpha)-induced NF-kappaB activation. This event correlates with
      MC160-induced IKK1 protein degradation, suggesting a mechanism for the above
      mentioned phenotype. IKK1 is stabilized when it associates with the cellular heat
      shock protein 90 (Hsp90). Here, Hsp90 overexpression restored IKK1 levels in
      MC160-expressing cells, suggesting that MC160 competitively interacted with
      Hsp90. In support of this, further investigation showed that a mutant MC160
      protein comprising only the C-terminal region (C protein) immunoprecipitated with
      Hsp90. In contrast, Hsp90 IP with a mutant MC160 protein consisting of only the N
      terminal tandem death effector domains (DEDs) (N protein) was dramatically
      decreased. Since cells expressing either the N or C mutant MC160 protein remained
      similarly resistant to TNF-alpha-induced NF-kappaB activation, the N mutant
      protein probably utilized a different mechanism for inhibiting NF-kappaB. One
      likely mechanism for the N protein lies in its association with the DED
      containing procaspase-8 protein, a cellular apoptosis precursor protein that
      regulates NF-kappaB activation. Here, IPs revealed that this association relied
      on the presence of the DED-containing N terminus of the MC160 protein but not the
      C-terminal portion. These interactions appear to have relevance with NF-kappaB
      activation, since the expression of the viral DEDs strongly inhibited procaspase
      8-mediated NF-kappaB activation, an event not substantially altered by the C
      protein. Thus, the MC160 protein utilizes at least two distinct mechanisms for
      impeding NF-kappaB activation, association with Hsp90 to result in IKK1 protein
      degradation or interaction with procaspase-8.

PMID- 19158251
TI  - Dual roles for an arginine-rich motif in specific genome recognition and
      localization of viral coat protein to RNA replication sites in flock house virus
      infected cells.
AB  - Assembly of many RNA viruses entails the encapsidation of multiple genome
      segments into a single virion, and underlying mechanisms for this process are
      still poorly understood. In the case of the nodavirus Flock House virus (FHV), a
      bipartite positive-strand RNA genome consisting of RNA1 and RNA2 is copackaged
      into progeny virions. In this study, we investigated whether the specific
      packaging of FHV RNA is dependent on an arginine-rich motif (ARM) located in the
      N terminus of the coat protein. Our results demonstrate that the replacement of
      all arginine residues within this motif with alanines rendered the resultant coat
      protein unable to package RNA1, suggesting that the ARM represents an important
      determinant for the encapsidation of this genome segment. In contrast,
      replacement of all arginines with lysines had no effect on RNA1 packaging.
      Interestingly, confocal microscopic analysis demonstrated that the RNA1 packaging
      deficient mutant did not localize to mitochondrial sites of FHV RNA replication
      as efficiently as wild-type coat protein. In addition, gain-of-function analyses
      showed that the ARM by itself was sufficient to target green fluorescent protein
      to RNA replication sites. These data suggest that the packaging of RNA1 is
      dependent on trafficking of coat protein to mitochondria, the presumed site of
      FHV assembly, and that this trafficking requires a high density of positive
      charge in the N terminus. Our results are compatible with a model in which
      recognition of RNA1 and RNA2 for encapsidation occurs sequentially and in
      distinct cellular microenvironments.

PMID- 19158252
TI  - Kaposi's sarcoma-associated herpesvirus upregulates angiogenin during infection
      of human dermal microvascular endothelial cells, which induces 45S rRNA
      synthesis, antiapoptosis, cell proliferation, migration, and angiogenesis.
AB  - Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is associated with the
      angioproliferative KS lesions characterized by spindle-shaped endothelial cells,
      inflammatory cells, cytokines, growth factors, and angiogenic factors. De novo
      KSHV infection of human microvascular dermal endothelial cells results in
      increased secretion of several growth factors, cytokines, chemokines, and
      angiogenic factors, and the multifunctional angiogenic protein angiogenin is one
      of them. KS tissue sections were positive for angiogenin, highlighting the
      importance of angiogenin in KS pathogenesis. Examination of KSHV-mediated
      angiogenin upregulation and secretion and potential outcomes revealed that during
      infection of primary endothelial cells, KSHV induced a time- and dose-dependent
      increase in angiogenin gene expression and protein secretion beginning as early
      as 8 h postinfection and lasting until the fifth day of our observation period.
      TIVE latently transformed cells (TIVE-LTC) latently infected with KSHV secreted
      high levels of angiogenin. Angiogenin was also detected in BCBL-1 cells (human B
      cells) carrying KSHV in a latent state. Significant induction of angiogenin was
      observed in cells expressing KSHV ORF73 (LANA-1; latent) and ORF74 (lytic) genes
      alone, and moderate induction was seen with the lytic KSHV ORF50 gene. Angiogenin
      bound to surface actin, internalized in a microtubule-independent manner, and
      translocated into the nucleus and nucleolus of infected cells. In addition, it
      increased 45S rRNA gene transcription, antiapoptosis, and proliferation of
      infected cells, thus demonstrating the multifunctional nature of KSHV-induced
      angiogenin. These activities were dependent on angiogenin nuclear translocation,
      which was inhibited by neomycin. Upregulation of angiogenin led to increased
      activation of urokinase plasminogen activator and generation of active plasmin,
      which facilitated the migration of endothelial cells toward chemoattractants,
      including angiogenin, and chemotaxis was prevented by the inhibition of
      angiogenin nuclear translocation. Treatment of KSHV-infected cell supernatants
      with antiangiogenin antibodies significantly inhibited endothelial tube
      formation, and inhibition of nuclear translocation of angiogenin also blocked the
      expression of KSHV-induced vascular endothelial growth factor C. Collectively,
      these results strongly suggest that by increasing infected endothelial cell 45S
      rRNA synthesis, proliferation, migration, and angiogenesis, KSHV-induced
      angiogenin could be playing a pivotal role in the pathogenesis of KSHV infection,
      including a contribution to the angioproliferative nature of KS lesions. Our
      studies suggested that LANA-1 and vGPCR play roles in KSHV-induced angiogenesis
      and that the angiogenic potential of vGPCR might also be due to its ability to
      induce angiogenin.

PMID- 19158253
TI  - Explaining fruit and vegetable intake using a consumer marketing tool.
AB  - In response to calls to reinvent the 5 A Day fruit and vegetable campaign, this
      study assesses the utility of VALS, a consumer-based audience segmentation tool
      that divides the U.S. population into groups leading similar lifestyles. The
      study examines whether the impact of theory of planned behavior (TPB) constructs
      varies across VALS groups in a cross-sectional sample of 1,588 U.S. adults. In a
      multigroup structural equation model, the VALS audience group variable moderated
      latent TPB relationships. Attitudes, subjective norms, and perceived behavioral
      control explained 57% to 70% of the variation in intention to eat fruit and
      vegetables across 5 different VALS groups. Perceived behavioral control and
      intention also predicted self-reported consumption behavior (R2 = 20% to 71%
      across VALS groups). Bivariate z tests were calculated to determine statistical
      differences in parameter estimates across groups. Nine of the bivariate z tests
      were statistically significant (p < or = .04), with standardized coefficients
      ranging from .05 to .70. These findings confirm the efficacy of using the TPB to
      explain variation in fruit and vegetable consumption as well as the validity of
      using a consumer-based algorithm to segment audiences for fruit and vegetable
      consumption messaging.

PMID- 19158254
TI  - Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle
      vasodilatation.
AB  - The influence of Glu298Asp endothelial nitric oxide synthase (eNOS) polymorphism
      in exercise-induced reflex muscle vasodilatation is unknown. We hypothesized that
      nonexercising forearm blood flow (FBF) responses during handgrip isometric
      exercise would be attenuated in individuals carrying the Asp298 allele. In
      addition, these responses would be mediated by reduced eNOS function and NO
      mediated vasodilatation or sympathetic vasoconstriction. From 287 volunteers
      previously genotyped, we selected 33 healthy individuals to represent three
      genotypes: Glu/Glu [n = 15, age 43 +/- 3 yr, body mass index (BMI) 22.9 +/- 0.3
      kg/m(2)], Glu/Asp (n = 9, age 41 +/- 3 yr, BMI 23.7 +/- 1.0 kg/m(2)), and Asp/Asp
      (n = 9, age 40 +/- 4 yr, BMI 23.5 +/- 0.9 kg/m(2)). Heart rate (HR), mean blood
      pressure (MBP), and FBF (plethysmography) were recorded for 3 min at baseline and
      3 min during isometric handgrip exercise. Baseline HR, MBP, FBF, and forearm
      vascular conductance (FVC) were similar among genotypes. FVC responses to
      exercise were significantly lower in Asp/Asp when compared with Glu/Asp and
      Glu/Glu (Delta = 0.07 +/- 0.14 vs. 0.64 +/- 0.20 and 0.57 +/- 0.09 units,
      respectively; P = 0.002). Further studies showed that intra-arterial infusion of
      NG-monomethyl-L-arginine (L-NMMA) did not change FVC responses to exercise in
      Asp/Asp, but significantly reduced FVC in Glu/Glu (Delta = 0.79 +/- 0.14 vs. 0.14
      +/- 0.09 units). Thus the differences between Glu/Glu and Asp/Asp were no longer
      observed (P = 0.62). l-NMMA + phentolamine increased similarly FVC responses to
      exercise in Glu/Glu and Asp/Asp (P = 0.43). MBP and muscle sympathetic nerve
      activity increased significant and similarly throughout experimental protocols in
      Glu/Glu and Asp/Asp. Individuals who are homozygous for the Asp298 allele of the
      eNOS enzyme have attenuated nonexercising muscle vasodilatation in response to
      exercise. This genotype difference is due to reduced eNOS function and NO
      mediated vasodilatation, but not sympathetic vasoconstriction.

PMID- 19158255
TI  - Heterogeneity of vaginal microbial communities within individuals.
AB  - Recent culture-independent studies have revealed that a healthy vaginal ecosystem
      harbors a surprisingly complex assemblage of microorganisms. However, the spatial
      distribution and composition of vaginal microbial populations have not been
      investigated using molecular methods. Here, we evaluated site-specific microbial
      composition within the vaginal ecosystem and examined the influence of sampling
      technique in detection of the vaginal microbiota. 16S rRNA gene clone libraries
      were prepared from samples obtained from different locations (cervix, fornix,
      outer vaginal canal) and by different methods (swabbing, scraping, lavaging) from
      the vaginal tracts of eight clinically healthy, asymptomatic women. The data
      reveal that the vaginal microbiota is not homogenous throughout the vaginal tract
      but differs significantly within an individual with regard to anatomical site and
      sampling method used. Thus, this study illuminates the complex structure of the
      vaginal ecosystem and calls for the consideration of microenvironments when
      sampling vaginal microbiota as a clinical predictor of vaginal health.

PMID- 19158256
TI  - Genetic profiles of fluoroquinolone-resistant Escherichia coli isolates obtained
      from patients with cystitis: phylogeny, virulence factors, PAIusp subtypes, and
      mutation patterns.
AB  - The low virulence of quinolone- and fluoroquinolone-resistant Escherichia coli
      strains is known, although the reasons for this remain unclear. We surveyed the
      mutation patterns of quinolone resistance determining regions (QRDRs),
      phylogenetic distribution, prevalence of 18 urovirulence genes, and PAIusp
      subtypes in 89 fluoroquinolone-resistant E. coli (FQREC) isolates obtained from
      patients with cystitis and compared them with those of their fluoroquinolone
      susceptible counterparts (FQSEC). Phylogenetic group B2 was significantly less
      prevalent in FQREC than in FQSEC (49% versus 78%; P=0.0138), but it still
      dominated, followed by phylogroup D (35%), in FQREC. When the prevalences of
      virulence factor (VF) genes were compared between FQREC and FQSEC, sfa/foc, cnf1,
      hly, kpsMT, ompT, ibeA, usp, and iroN showed significantly lower prevalences in
      FQREC than in FQSEC (1.1% versus 24% [P<0.0001], 0% versus 29% [P<0.0001], 7.9%
      versus 33% [P<0.0001], 74% versus 90% [P=0.01], 71% versus 87% [P=0.017], 5.6%
      versus 37% [P<0.0001], 54% versus 82% [P<0.0001], and 7.9% versus 32% [P=0.0001],
      respectively), whereas aer, iha, and ETTT showed significantly higher prevalences
      in FQREC (85% versus 36% [P<0.0001], 66% versus 29% [P<0.0001], and 53% versus
      16% [P<0.0001], respectively). Furthermore, a similar difference in prevalences
      of uropathogenic VF genes was seen between FQREC and FQSEC in phylogroup B2. This
      indicated that the low virulence in FQREC was intimately correlated with a lesser
      distribution of VFs in phylogroup B2, which dominated in FQREC and FQSEC. It was
      interesting that the mutation pattern of Ser83Leu and Asp87Asn encoded in gyrA
      and Ser80Ile and Glu84Val encoded in parC was frequently found in FQREC isolates
      that belonged to phylogroup B2 and that most of these isolates showed PAIusp
      subtype 2a. PAIusp subtypes 1a, 1b, and 2b, which were frequently seen in FQSEC,
      were rarely found in FQREC. These results suggested that the acquisition of
      fluoroquinolone resistance, e.g., mutations in QRDRs, might be a specific event
      in limited strains, such as those that possess PAIusp subtype 2a in phylogroup
      B2.

PMID- 19158257
TI  - Incidence, virulence factors, and clonality among clinical strains of non-O1, non
      O139 Vibrio cholerae isolates from hospitalized diarrheal patients in Kolkata,
      India.
AB  - The incidence of Vibrio cholerae non-O1, non-O139 strains from hospitalized
      patients with acute diarrhea constituted 27.4% (n = 54) of the total 197 V.
      cholerae strains isolated from patients in Kolkata, India, in 2003. Of 197
      strains, 135 were identified as O1 serotype Ogawa and 2 were identified as O139.
      In the same time period, six O1 background rough strains that possessed all known
      virulence factors were identified. Serotype analysis of the non-O1, non-O139
      strains placed 42 strains into 19 serogroups, while 12 remained O nontypeable
      (ONT); the existing serotyping scheme involved antisera to 206 serogroups.
      Detection of a good number of ONT strains suggested that additional serogroups
      have arisen that need to be added to the current serotyping scheme. The non-O1,
      non-O139 strains were nontoxigenic except for an O36 strain (SC124), which
      regulated expression of cholera toxin as O1 classical strains did. Additionally,
      strain SC124 carried alleles of tcpA and toxT that were different from those of
      the O1 counterpart, and these were also found in five clonally related strains
      belonging to different serogroups. Strains carrying tcpA exhibited higher
      colonization in an animal model compared to those lacking tcpA. PCR-based
      analyses revealed remarkable variations in the distribution of other virulence
      factors, including hlyA, rtxA, Vibrio seventh pandemic island I (VSP-I), VSP-II,
      and type III secretion system (TTSS). Most strains contained hlyA (87%) and rtxA
      (81.5%) and secreted cytotoxic factors when grown in vitro. Approximately one
      third of the strains (31.5%) contained the TTSS gene cluster, and most of these
      strains were more motile and hemolytic against rabbit erythrocytes. Partial
      nucleotide sequence analysis of the TTSS-containing strains revealed silent
      nucleotide mutations within vcsN2 (type III secretion cytoplasmic ATPase),
      indicating functional conservation of the TTSS apparatus.

PMID- 19158258
TI  - Polymorphism in the CagA EPIYA motif impacts development of gastric cancer.
AB  - Helicobacter pylori causes diseases ranging from gastritis to peptic ulcer
      disease to gastric cancer. Geographically, areas with high incidences of H.
      pylori infection often overlap with areas with high incidences of gastric cancer,
      which remains one of the leading causes of cancer-related deaths worldwide.
      Strains of H. pylori that carry the virulence factor cytotoxin-associated gene A
      (cagA) are much more likely to be associated with the development of gastric
      cancer. Moreover, particular C-terminal polymorphisms in CagA vary by geography
      and have been suggested to influence disease development. We conducted a large
      scale molecular epidemiologic analysis of South Korean strains and herein report
      a statistical link between the East Asian CagA EPIYA-ABD genotype and the
      development of gastric cancer. Characterization of a subset of the Korean
      isolates showed that all strains from cancer patients expressed and delivered
      phosphorylatable CagA to host cells, whereas the presence of the cagA gene did
      not strictly correlate to expression and delivery of CagA in all noncancer
      strains.

PMID- 19158259
TI  - First evaluation of the WASP, a new automated microbiology plating instrument.
AB  - Many laboratories are experiencing growing shortages of trained microbiology
      technologists and technicians. Consequently, there is considerable interest in
      new automation that could potentially lessen labor demands for specimen
      processing. In this study, we present the first published evaluation of a new
      microbiology instrument, the Walk Away Specimen Processor (WASP), manufactured by
      Copan, Inc., in which we evaluated cross-contamination, the accuracy of plating,
      and the quality of the results. The absence of cross-contamination was
      demonstrated by plating a total of 200 alternating inoculated and sterile
      specimen tubes. The ability of the WASP to subculture enrichment broths was
      evaluated with 106 Lim broth specimens, with the results being identical to those
      obtained by testing by routine methods. Plating of urine specimens with the WASP
      was compared to plating with the Dynacon Inoculab instrument. Three hundred
      specimens were plated in duplicate on both instruments with 1-microl loops, and
      293 specimens were plated in duplicate on both instruments with 10-microl loops.
      The results of duplicate plating with the same instrument (replicate plating) and
      of the consensus agreement between the two instruments were compared. The
      replicate plating results were comparable for both instruments, while the WASP
      had more specimens with significant results than the Inoculab with the 1-microl
      loop only. Lastly, for the plating of 113 specimens in ESwab tubes, the manual
      method and WASP plating each yielded 90 potential pathogens. In summary, we
      report the first evaluation of a new microbiology specimen-plating instrument,
      the WASP, which offers opportunities for the automated plating of microbiology
      specimens to an extent that has not been possible to date.

PMID- 19158260
TI  - Isolation, antimicrobial resistance, and virulence genes of Pasteurella multocida
      strains from swine in China.
AB  - A total of 233 isolates of Pasteurella multocida were obtained from 2,912 cases
      of clinical respiratory disease in pigs in China, giving an isolation rate of
      8.0%. Serogroup A P. multocida isolates were isolated from 92 cases (39.5%), and
      serogroup D isolates were isolated from 128 cases (54.9%); 12 isolates (5.2%)
      were untypeable. P. multocida was the fourth most frequent pathogenic bacterium
      recovered from the respiratory tract, after Streptococcus suis, Haemophilus
      parasuis, and Escherichia coli. All isolates were characterized for their
      susceptibilities to 20 antibiotics and the presence of 19 genes for virulence
      factors (VFs). The frequency of antimicrobial resistance among P. multocida
      isolates from swine in China was higher than that reported among P. multocida
      isolates from swine in from other countries, and 93.1% of the isolates showed
      multiple-drug resistance. There was a progressive increase in the rate of
      multiresistance to more than seven antibiotics, from 16.2% in 2003 to 62.8% in
      2007. The resistance profiles suggested that cephalosporins, florfenicol, and
      fluoroquinolones were the drugs most likely to be active against P. multocida.
      Use of PCR showed that colonization factors (ptfA, fimA, and hsf-2), iron
      acquisition factors, sialidases (nanH), and outer membrane proteins occurred in
      most porcine strains. The VFs pfhA, tadD, toxA, and pmHAS were each present in
      <50% of strains. The various VFs exhibited distinctive associations with
      serogroups: concentrated in serogroup A, concentrated in serogroup D, or
      occurring jointly in serogroups A and D. These findings provide novel insights
      into the epidemiological characteristics of porcine P. multocida isolates and
      suggest that the potential threat of such multiresistant bacteria in food
      producing animals should not be neglected.

PMID- 19158261
TI  - Multiplexed genotyping of methicillin-resistant Staphylococcus aureus isolates by
      use of padlock probes and tag microarrays.
AB  - We developed and tested a ligase-based assay for simultaneous probing of core
      genome diversity and typing of methicillin resistance determinants in
      Staphylococcus aureus isolates. This assay uses oligonucleotide padlock probes
      whose two ends are joined through ligation when they hybridize to matching target
      DNA. Circularized probes are subsequently amplified by PCR with common primers
      and analyzed by using a microarray equipped with universal tag probes. Our set of
      padlock probes includes oligonucleotides targeting diagnostic regions in the
      mecA, ccrB, and ccrC genes of the SCCmec cassette in methicillin-resistant S.
      aureus (MRSA). These probes determine the presence and type of SCCmec cassettes
      (i.e., SCCmec types I to VI). Additional oligonucleotides interrogate a number of
      highly informative single nucleotide polymorphisms retrieved from a multilocus
      sequence typing (MLST) database. These latter probes enable the exploration of
      isolates' phylogenetic affiliation with clonal lineages of MRSA as revealed by
      MLST. The described assay enables multiplexed genotyping of MRSA based on a
      single-tube reaction. With a set of clinical isolates of MRSA and methicillin
      susceptible S. aureus (n=66), 100% typeability and 100% accuracy were achieved.
      The assay described here provides valuable genotypic information that may
      usefully complement existing genotyping procedures. Moreover, the assay is easily
      extendable by incorporating additional padlock probes and will be valuable for
      the quick and cost-effective probing of large numbers of polymorphisms at
      different genomic locations, such as those ascertained through currently ongoing
      mutation discovery and genome resequencing projects.

PMID- 19158262
TI  - Performance of microcalorimetry for early detection of methicillin resistance in
      clinical isolates of Staphylococcus aureus.
AB  - We describe a calorimetric assay for the detection of methicillin-resistant
      Staphylococcus aureus (MRSA) within 5 h. Microbial heat was calculated in culture
      with and without cefoxitin. Among 30 genetically distinct clinical isolates,
      19/20 MRSA (95%) and 10/10 methicillin-susceptible Staphylococcus aureus (100%)
      were correctly identified. Microcalorimetry may be useful for rapid MRSA
      screening.

PMID- 19158263
TI  - Comparison of automated microarray detection with real-time PCR assays for
      detection of respiratory viruses in specimens obtained from children.
AB  - Respiratory virus infections are a major health concern and represent the primary
      cause of testing consultation and hospitalization for young children. We
      developed and compared two assays that allow the detection of up to 23 different
      respiratory viruses that frequently infect children. The first method consisted
      of single TaqMan quantitative real-time PCR assays in a 96-well-plate format. The
      second consisted of a multiplex PCR followed by primer extension and microarray
      hybridization in an integrated molecular diagnostic device, the Infiniti
      analyzer. Both of our assays can detect adenoviruses of groups A, B, C, and E;
      coronaviruses HKU1, 229E, NL63, and OC43; enteroviruses A, B, C, and D;
      rhinoviruses of genotypes A and B; influenza viruses A and B; human
      metapneumoviruses (HMPV) A and B, human respiratory syncytial viruses (HRSV) A
      and B; and parainfluenza viruses of types 1, 2, and 3. These tests were used to
      identify viruses in 221 nasopharyngeal aspirates obtained from children
      hospitalized for respiratory tract infections. Respiratory viruses were detected
      with at least one of the two methods in 81.4% of the 221 specimens: 10.0% were
      positive for HRSV A, 38.0% for HRSV B, 13.1% for influenzavirus A, 8.6% for any
      coronaviruses, 13.1% for rhinoviruses or enteroviruses, 7.2% for adenoviruses,
      4.1% for HMPV, and 1.5% for parainfluenzaviruses. Multiple viral infections were
      found in 13.1% of the specimens. The two methods yielded concordant results for
      94.1% of specimens. These tests allowed a thorough etiological assessment of
      respiratory viruses infecting children in hospital settings and would assist
      public health interventions.

PMID- 19158264
TI  - Multilocus sequence types associated with neonatal group B streptococcal sepsis
      and meningitis in Canada.
AB  - Group B streptococci (GBS), a leading cause of neonatal sepsis and meningitis,
      are transferred to neonates from colonized mothers during childbirth. Prior
      studies using multilocus sequence typing (MLST) have found specific GBS clones
      (e.g., sequence type 17 [ST-17]) to be associated with neonatal disease in
      several geographic locations. Few population-based studies, however, have been
      conducted to determine the frequency of disease caused by specific GBS clones.
      MLST was used to assess the genetic diversity of 192 GBS strains from neonates
      and young children identified by population-based surveillance in Alberta,
      Canada, from 1993 to 2002. Comparisons were made to 232 GBS strains collected
      from colonized pregnant women, and all strains were characterized for one of nine
      capsule (cps) genotypes. A total of 47 STs were identified, and more than 80% of
      GBS strains were represented by 7 STs that have been shown to predominate in
      other populations. ST-17 and ST-19 were more prevalent in strains causing early
      onset disease (EOD) and late onset disease (LOD) than from pregnant women,
      whereas STs 1, 12, and 23 were more common in pregnant women. In addition, ST-17
      strains and close relatives more frequently caused meningitis than sepsis and LOD
      versus EOD in this population of neonates. Further research is required to better
      understand why strains belonging to the ST-17 phylogenetic lineage are more
      likely to cause both LOD and meningitis and may provide clues into the
      pathogenesis of these conditions.

PMID- 19158265
TI  - Epidemiologic study of influenza infection in Okinawa, Japan, from 2001 to 2007:
      changing patterns of seasonality and prevalence of amantadine-resistant influenza
      A virus.
AB  - To clarify seasonal influenza patterns and the prevalence of amantadine-resistant
      influenza A viruses in Okinawa, located at the southern extremity of Japan in a
      subtropical climate, we conducted a laboratory-based study of influenza virus
      infections from 2001 to 2007. The annual outbreaks tended to show two peaks in
      Okinawa, in summer and winter, although the main islands of Japan, located in a
      temperate climate area, showed only winter influenza activity. Epidemic types and
      subtypes in Okinawa mostly matched those on the main islands of Japan in winter
      and those in Taiwan in summer. Rates of amantadine resistance dramatically
      increased, from 7.3% in the November 2002-to-March 2003 season to 90.0% in summer
      2005, and a similarly high rate of resistance continued for the rest of the study
      period. Phylogenetic analysis of the hemagglutinin gene of A/H3N2 isolates
      collected from 2002 to 2007 revealed a monophyletic lineage that was divided into
      four period groups. Each group included amantadine-sensitive and -resistant
      viruses within independent clusters. In the November 2005-to-March 2006 season,
      all of the amantadine-resistant viruses were clustered in clade N, with dual
      (position 193 and 225) amino acid mutations in their HA1 subunits. In 2005, clade
      N amantadine-resistant viruses existed in Okinawa several months before the
      circulation of this clade on the main islands of Japan. In conclusion,
      surveillance in Okinawa to monitor influenza virus circulation is important for
      elucidating the dynamics of virus transmission in a border area between temperate
      and subtropical areas, as Okinawa is one of the best sentinel points in Japan.

PMID- 19158266
TI  - Clinical and microbiological characteristics of severe Streptococcus pyogenes
      disease in Europe.
AB  - In an attempt to compare the epidemiology of severe Streptococcus pyogenes
      infection within Europe, prospective data were collected through the Strep-EURO
      program. Surveillance for severe cases of S. pyogenes infection diagnosed during
      2003 and 2004 was undertaken in 11 countries across Europe by using a
      standardized case definition and questionnaire. Patient data as well as bacterial
      isolates were collected and characterized by T and M/emm typing, and selected
      strains were analyzed for the presence of superantigen genes. Data were analyzed
      to compare the clinical and microbiological patterns of the infections across the
      participating countries. A total of 4,353 isolates were collected from 5,521
      cases with severe S. pyogenes infections who were identified. A wide diversity of
      M/emm types (n = 104) was found among the S. pyogenes clinical isolates, but the
      M/emm type distribution varied broadly between participating countries. The 10
      most predominant M/emm types were M/emm type 1 (M/emm1), M/emm28, M/emm3,
      M/emm89, M/emm87, M/emm12, M/emm4, M/emm83, M/emm81, and M/emm5, in descending
      order. A correlation was found between some specific disease manifestations, the
      age of the patients, and the emm types. Although streptococcal toxic shock
      syndrome and necrotizing fasciitis were caused by a large number of types, they
      were particularly associated with M/emm1 and M/emm3. The emm types included in
      the 26-valent vaccine under development were generally well represented in the
      present material; 16 of the vaccine types accounted for 69% of isolates. The
      Strep-EURO collaborative program has contributed to enhancement of the knowledge
      of the spread of invasive disease caused by S. pyogenes within Europe and
      encourages future surveillance by the notification of cases and the
      characterization of strains, which are important for vaccination strategies and
      other health care issues.

PMID- 19158267
TI  - Changes in genetic diversity of the Bordetella pertussis population in the United
      Kingdom between 1920 and 2006 reflect vaccination coverage and emergence of a
      single dominant clonal type.
AB  - Pertussis (whooping cough) is a potentially fatal respiratory disease caused by
      the bacterium Bordetella pertussis. Despite effective vaccination programs, there
      has been concern in some developed countries that pertussis cases are on the
      increase. We characterized 703 clinical B. pertussis isolates collected in the
      United Kingdom between 1920 and 2006 using multilocus variable-number tandem
      repeat analysis (MLVA), pertactin (prnA) and pertussis toxin (ptxA) genotyping,
      and serotyping. The results showed that the genetic diversity of the bacterial
      population decreased during periods of high vaccine coverage. However, it was
      elevated between 1977 and 1986, when vaccine coverage in the United Kingdom was
      low and epidemics occurred. A high proportion of MLVA types during this epidemic
      period were novel, and the prnA(2) and prnA(3) alleles were seen for the first
      time in the United Kingdom. MLVA-27 appeared in 1982, was codominant during the
      1998-to-2001 period, and comprised approximately 70% of isolates during both the
      2002-to-2004 and the 2005-to-2006 periods. The United Kingdom is dominated
      currently by an MLVA-27 prnA(2) ptxA(1) serotype Fim3 clonal type. Even during
      recent periods dominated by MLVA-27, many novel types were found at low
      frequencies, suggesting that either there are a large number of uncommon MLVA
      types circulating at low frequencies or new types are constantly arising. This
      supports a hypothesis that MLVA-27 is under some form of positive selection
      conferring increased survival in a highly vaccinated population. There has been
      no significant change to the bacterial population in the first 2 years since the
      United Kingdom switched from a whole-cell to an acellular vaccine.

PMID- 19158268
TI  - Antiapoptotic role for ornithine decarboxylase during oocyte maturation.
AB  - Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine
      biosynthesis, is a nonredundant and essential gene in all eukaryotes. During the
      mitotic cell cycle, ODC exhibits two activity peaks: one at the G(1)/S transition
      and one during the G(2)/M transition. The physiological role of this cell cycle
      dependent ODC activity dynamic is not clear. Previous studies have reported a
      significant elevation of ODC activity during Xenopus oocyte maturation, which
      resembles mitotic G(2)/M transition. In order to study the roles of ODC activity
      in the oocytes, we utilized antisense morpholino (xODC mo) oligonucleotides to
      inhibit ODC translation. We report here that xODC mo abolished ODC activity
      increase during oocyte maturation. xODC mo-injected oocytes underwent germinal
      vesicle breakdown, emitted the first polar body, and reached metaphase II, thus
      completing nuclear maturation. However, the metaphase II oocytes exhibited high
      levels of reactive oxygen species and became apoptotic. When transferred to host
      frogs and subsequently ovulated, these eggs were fertilized but exhibited embryo
      fragmentation. Translation of ODC is therefore integral to cytoplasmic
      maturation, protecting metaphase II oocytes from reactive oxygen species-induced
      apoptosis.

PMID- 19158269
TI  - A conserved insulator that recruits CTCF and cohesin exists between the closely
      related but divergently regulated interleukin-3 and granulocyte-macrophage colony
      stimulating factor genes.
AB  - The human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating
      factor (GM-CSF, or CSF2) gene cluster arose by duplication of an ancestral gene.
      Although just 10 kb apart and responsive to the same signals, the IL-3 and GM-CSF
      genes are nevertheless regulated independently by separate, tissue-specific
      enhancers. To understand the differential regulation of the IL-3 and GM-CSF genes
      we have investigated a cluster of three ubiquitous DNase I-hypersensitive sites
      (DHSs) located between the two genes. We found that each site contains a
      conserved CTCF consensus sequence, binds CTCF, and recruits the cohesin subunit
      Rad21 in vivo. The positioning of these sites relative to the IL-3 and GM-CSF
      genes and their respective enhancers is conserved between human and mouse,
      suggesting a functional role in the organization of the locus. We found that
      these sites effectively block functional interactions between the GM-CSF enhancer
      and either the IL-3 or the GM-CSF promoter in reporter gene assays. These data
      argue that the regulation of the IL-3 and the GM-CSF promoters depends on the
      positions of their enhancers relative to the conserved CTCF/cohesin-binding
      sites. We suggest that one important role of these sites is to enable the
      independent regulation of the IL-3 and GM-CSF genes.

PMID- 19158270
TI  - Dynamic histone variant exchange accompanies gene induction in T cells.
AB  - Changes in chromatin composition are often a prerequisite for gene induction.
      Nonallelic histone variants have recently emerged as key players in
      transcriptional control and chromatin modulation. While the changes in chromatin
      accessibility and histone posttranslational modification (PTM) distribution that
      accompany gene induction are well documented, the dynamics of histone variant
      exchange that parallel these events are still poorly defined. In this study, we
      have examined the changes in histone variant distribution that accompany
      activation of the inducible CD69 and heparanase genes in T cells. We demonstrate
      that the chromatin accessibility increases that accompany the induction of both
      of these genes are not associated with nucleosome loss but instead are paralleled
      by changes in histone variant distribution. Specifically, induction of these
      genes was paralleled by depletion of the H2A.Z histone variant and concomitant
      deposition of H3.3. Furthermore, H3.3 deposition was accompanied by changes in
      PTM patterns consistent with H3.3 enriching or depleting different PTMs upon
      incorporation into chromatin. Nevertheless, we present evidence that these H3.3
      borne PTMs can be negated by recruited enzymatic activities. From these
      observations, we propose that H3.3 deposition may both facilitate chromatin
      accessibility increases by destabilizing nucleosomes and compete with recruited
      histone modifiers to alter PTM patterns upon gene induction.

PMID- 19158271
TI  - A Rac GTPase-activating protein, MgcRacGAP, is a nuclear localizing signal
      containing nuclear chaperone in the activation of STAT transcription factors.
AB  - In addition to their pleiotropic functions under physiological conditions,
      transcription factors STAT3 and STAT5 also have oncogenic activities, but how
      activated STATs are transported to the nucleus has not been fully understood.
      Here we show that an MgcRacGAP mutant lacking its nuclear localizing signal (NLS)
      blocks nuclear translocation of p-STATs both in vitro and in vivo. Unlike wild
      type MgcRacGAP, this mutant did not promote complex formation of phosphorylated
      STATs (p-STATs) with importin alpha in the presence of GTP-bound Rac1, suggesting
      that MgcRacGAP functions as an NLS-containing nuclear chaperone. We also
      demonstrate that mutants of STATs lacking the MgcRacGAP binding site (the strand
      betab) are hardly tyrosine phosphorylated after cytokine stimulation.
      Intriguingly, mutants harboring small deletions in the C'-adjacent region (betab
      betac loop region) of the strand betab became constitutively active with the
      enhanced binding to MgcRacGAP. The molecular basis of this phenomenon will be
      discussed, based on the computer-assisted tertiary structure models of STAT3.
      Thus, MgcRacGAP functions as both a critical mediator of STAT's tyrosine
      phosphorylation and an NLS-containing nuclear chaperone of p-STATs.

PMID- 19158272
TI  - Selective accumulation of aggregation-prone proteasome substrates in response to
      proteotoxic stress.
AB  - Conditions causing an increase in misfolded or aberrant proteins can impair the
      activity of the ubiquitin/proteasome system (UPS). This observation is of
      particular interest, given the fact that proteotoxic stress is closely associated
      with a large variety of disorders. Although impairment of the UPS appears to be a
      general consequence of proteotoxic insults, the underlying mechanisms remain
      enigmatic. Here, we show that heat shock-induced proteotoxic stress resulted in
      conjugation of ubiquitin to detergent-insoluble protein aggregates, which
      coincided with reduced levels of free ubiquitin and impediment of ubiquitin
      dependent proteasomal degradation. Interestingly, whereas soluble proteasome
      substrates returned to normal levels after a transient accumulation, the levels
      of an aggregation-prone substrate remained high even when the free ubiquitin
      levels were restored. Consistently, overexpression of ubiquitin prevented
      accumulation of soluble but not aggregation-prone substrates in thermally
      stressed cells. Notably, cells were also unable to resume degradation of
      aggregation-prone substrates after treatment with the translation inhibitor
      puromycin, indicating that selective accumulation of aggregation-prone proteins
      is a consistent feature of proteotoxic stress. Our data suggest that the failure
      of the UPS to clear aggregated proteins in the aftermath of proteotoxic stress
      episodes may contribute to the selective deposition of aggregation-prone proteins
      in conformational diseases.

PMID- 19158273
TI  - Topology of mammalian isoprenylcysteine carboxyl methyltransferase determined in
      live cells with a fluorescent probe.
AB  - Isoprenylcysteine carboxyl methyltransferase (Icmt) is a highly conserved enzyme
      that methyl esterifies the alpha carboxyl group of prenylated proteins including
      Ras and related GTPases. Methyl esterification neutralizes the negative charge of
      the prenylcysteine and thereby increases membrane affinity. Icmt is an integral
      membrane protein restricted to the endoplasmic reticulum (ER). The Saccharomyces
      cerevisiae ortholog, Ste14p, traverses the ER membrane six times. We used a novel
      fluorescent reporter to map the topology of human Icmt in living cells. Our
      results indicate that Icmt traverses the ER membrane eight times, with both N and
      C termini disposed toward the cytosol and with a helix-turn-helix structure
      comprising transmembrane (TM) segments 7 and 8. Several conserved amino acids
      that map to cytoplasmic portions of the enzyme are critical for full enzymatic
      activity. Mammalian Icmt has an N-terminal extension consisting of two TM
      segments not found in Ste14p and therefore likely to be regulatory. Icmt is a
      target for anticancer drug discovery, and these data may facilitate efforts to
      develop small-molecule inhibitors.

PMID- 19158274
TI  - Key role for activin B in cellular transformation after loss of the von Hippel
      Lindau tumor suppressor.
AB  - The von Hippel-Lindau tumor suppressor gene (VHL) is mutated in clear cell renal
      cell carcinomas (RCC), leading to the activation of hypoxia-inducible factor
      (HIF)-mediated gene transcription. Several VHL/HIF targets, such as glycolysis,
      angiogenesis, cell growth, and chemotaxis of tumor cells, have been implicated in
      the transformed phenotype of RCC-regulating properties. Here, we show that VHL
      suppresses key features of cell transformation through downregulation of the HIF
      dependent expression of activin B, a member of the transforming growth factor
      beta superfamily. Activin B expression is repressed by restoration of VHL in VHL
      deficient RCC cells and upregulated by hypoxia. RCC tumor samples show increased
      expression of activin B compared to that in the normal kidney. VHL increases cell
      adhesion to the extracellular matrix, promotes cell flattening, and reduces
      invasiveness. These effects are completely phenocopied by RNA interference
      mediated knockdown of activin B and reverted by treatment with recombinant
      activin B. Finally, knockdown of activin B reduces tumor growth of RCC cells in
      nude mice. Our data indicate that activin B is a key mediator of VHL/HIF-induced
      transformation in RCC.

PMID- 19158275
TI  - Protein kinase C-dependent phosphorylation regulates the cell cycle-inhibitory
      function of the p73 carboxy terminus transactivation domain.
AB  - The transcription factor p73, a member of the p53 family of proteins, is involved
      in the regulation of cell cycle progression and apoptosis. However, the
      regulatory mechanisms controlling the distinct roles for p73 in these two
      processes have remained unclear. Here, we report that p73 is able to induce cell
      cycle arrest independently of its amino-terminal transactivation domain, whereas
      this domain is crucial for p73 proapoptotic functions. We also characterized a
      second transactivation domain in the carboxy terminus of p73 within amino acid
      residues 381 to 399. This carboxy terminus transactivation domain was found to
      preferentially regulate genes involved in cell cycle progression. Moreover, its
      activity is regulated throughout the cell cycle and modified by protein kinase C
      dependent phosphorylation at serine residue 388. Our results suggest that this
      novel posttranslational modification within the p73 carboxy terminus
      transactivation domain is involved in the context-specific guidance of p73 toward
      the selective induction of cell cycle arrest.

PMID- 19158276
TI  - Chromatin-specific remodeling by HMGB1 and linker histone H1 silences
      proinflammatory genes during endotoxin tolerance.
AB  - Epigenetic silencing of tumor necrosis factor alpha (TNF-alpha) and interleukin
      1beta (IL-1beta) transcription occurs in blood leukocytes of animals and humans
      after the initiation of severe systemic inflammation (SSI). We previously
      reported that the epigenetic signature requires induction of NF-kappaB factor
      RelB, which directs histone H3K9 dimethylation, disrupts assembly of
      transcription activator NF-kappaB p65, and induces a sustained switch from the
      euchromatin to heterochromatin. Here, we report the novel findings that
      intracellular high mobility group box 1 protein (HMGB1) and nucleosome linker
      histone H1 protein are necessary components of endotoxin-mediated silencing of
      TNF-alpha in THP-1 human promonocytes. HMGB1 binds the TNF-alpha promoter during
      transcription silencing and promotes assembly of the repressor RelB. Depletion of
      HMGB1 by small interfering RNA results in dissociation of RelB from the promoter
      and partially restores TNF-alpha transcription. Histone H1, which typically
      displaces HMGB1 from nucleosomal DNA, also binds concomitantly with HMGB1 to the
      heterochromatin of the silenced TNF-alpha promoter. Combined knockdown of HMGB1
      and H1 restores binding of the transcriptionally active NF-kappaB p65 and
      reestablishes TNF-alpha mRNA levels. Chromatin reimmunoprecipitation experiments
      demonstrate that HMGB1 and H1 are likely recruited to TNF-alpha sequences
      independently and that their binding correlates with histone H3K9 dimethylation,
      as inhibition of histone methylation blocks HMGB1 and H1 binding. Moreover, HMGB1
      and H1-mediated chromatin modifications are gene specific during endotoxin
      silencing in that they also bind and repress acute proinflammatory IL-1beta,
      while no binding nor repression of antiinflammatory IkappaBalpha is observed.
      Finally, we find that H1 and HMGB1 bind to the TNF-alpha a promoter in human
      leukocytes obtained from patients with SSI. We conclude proinflammatory HMGB1 and
      structural nucleosome linker H1 couple as a component of the epigenetic complex
      that silences acute proinflammatory TNF-alpha during the assembly of
      heterochromatin in the SSI phenotype.

PMID- 19158277
TI  - Cold-inducible RNA-binding protein bypasses replicative senescence in primary
      cells through extracellular signal-regulated kinase 1 and 2 activation.
AB  - Embryonic stem cells are immortalized cells whose proliferation rate is
      comparable to that of carcinogenic cells. To study the expression of embryonic
      stem cell genes in primary cells, genetic screening was performed by infecting
      mouse embryonic fibroblasts (MEFs) with a cDNA library from embryonic stem cells.
      Cold-inducible RNA-binding protein (CIRP) was identified due to its ability to
      bypass replicative senescence in primary cells. CIRP enhanced extracellular
      signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, and treatment with an
      MEK inhibitor decreased the proliferation caused by CIRP. In contrast to CIRP
      upregulation, CIRP downregulation decreased cell proliferation and resulted in
      inhibition of phosphorylated ERK1/2 inhibition. This is the first evidence that
      ERK1/2 activation, through the same mechanism as that described for a Val12
      mutant K-ras to induce premature senescence, is able to bypass senescence in the
      absence of p16(INK4a), p21(WAF1), and p19(ARF) upregulation. Moreover, these
      results show that CIRP functions by stimulating general protein synthesis with
      the involvement of the S6 and 4E-BP1 proteins. The overall effect is an increase
      in kinase activity of the cyclin D1-CDK4 complex, which is in accordance with the
      proliferative capacity of CIRP MEFs. Interestingly, CIRP mRNA and protein were
      upregulated in a subgroup of cancer patients, a finding that may be of relevance
      for cancer research.

PMID- 19158278
TI  - Regulation of cell-cell adhesion by Abi/Diaphanous complexes.
AB  - Actin polymerization provides the driving force for the formation of cell-cell
      junctions and is mediated by two types of actin nucleators, Arp2/3 and formins.
      Proteins required for coordinately linking cadherin-mediated adhesion to Arp2/3
      dependent versus formin-dependent nucleation have yet to be defined. Here we show
      a role for Abi, the Abi-binding partner Nap1, and the Nap1-binding protein Sra1
      in the regulation of cadherin-dependent adhesion. We found that Abi, which is
      known to interact with Wave, leading to activation of the Arp2/3 complex, is also
      capable of interacting with the Diaphanous (Dia)-related formins in the absence
      of Wave. Knockdown of Abi, Nap1, Sra1, or Dia markedly inhibited cell-cell
      junctions, whereas knockdown of Wave or Arp2/3 produced mild and transient
      phenotypes. Dia and Abi colocalized with beta-catenin at cell-cell junctions.
      Further, Dia and Wave bound to overlapping sites on Abi1, and Wave competed with
      Dia for Abi1 binding. Notably, an active Dia1 C-terminal fragment that localizes
      to cell-cell junctions rescued the abnormal junctions induced by depletion of Abi
      or Nap1 in epithelial cells. These findings uncover a novel link between cadherin
      mediated adhesion and the regulation of actin dynamics through the requirement
      for an Abi/Dia complex for the formation and stability of cell-cell junctions.

PMID- 19158279
TI  - Phosphorylation of Fli1 at threonine 312 by protein kinase C delta promotes its
      interaction with p300/CREB-binding protein-associated factor and subsequent
      acetylation in response to transforming growth factor beta.
AB  - Previous studies have shown that transforming growth factor beta (TGF-beta)
      induced collagen gene expression involves acetylation-dependent dissociation from
      the human alpha2(I) collagen (COL1A2) promoter of the transcriptional repressor
      Fli1. The goal of this study was to elucidate the regulatory steps preceding the
      acetylation of Fli1. We first showed that TGF-beta induces Fli1 phosphorylation
      on a threonine residue(s). The major phosphorylation site was localized to
      threonine 312 located in the DNA binding domain of Fli1. Using several
      independent approaches, we demonstrated that Fli1 is directly phosphorylated by
      protein kinase C delta (PKC delta). Additional experiments showed that in
      response to TGF-beta, PKC delta is recruited to the collagen promoter to
      phosphorylate Fli1 and that this step is a prerequisite for the subsequent
      interaction of Fli1 with p300/CREB-binding protein-associated factor (PCAF) and
      an acetylation event. The phosphorylation of endogenous Fli1 preceded its
      acetylation in response to TGF-beta stimulation, and the blockade of PKC delta
      abrogated both the phosphorylation and acetylation of Fli1 in dermal fibroblasts.
      Promoter studies showed that a phosphorylation-deficient mutant of Fli1 exhibited
      an increased inhibitory effect on the COL1A2 gene, which could not be reversed by
      the forced expression of PCAF or PKC delta. These data strongly suggest that the
      phosphorylation-acetylation cascade triggered by PKC delta represents the primary
      mechanism whereby TGF-beta regulates the transcriptional activity of Fli1 in the
      context of the collagen promoter.

PMID- 19158282
TI  - Detection of (1-->3)-beta-D-glucan as an adjunct to diagnosis in a mixed
      population with uncommon proven invasive fungal diseases or with an unusual
      clinical presentation.
AB  - This single-center observational prospective study evaluated the performance of
      (1-->3)-beta-D-glucan as an adjunct diagnostic tool in 12 patients with proven
      invasive fungal disease with different risk factors. The infections were due to
      either uncommon fungal pathogens such as dematiaceous molds (Scedosporium
      apiospermum, Alternaria infectoria, and Cladosporium macrocarpum) and hyaline
      septate molds (Fusarium solani and Blastoschizomyces capitatus) or Aspergillus
      spp. with unusual clinical presentations.

PMID- 19158283
TI  - Decline in cases of rotavirus gastroenteritis presenting to The Children's
      Hospital of Philadelphia after introduction of a pentavalent rotavirus vaccine.
AB  - A pentavalent rotavirus vaccine for infants became available in the United States
      in February 2006. By 2007, vaccination rates nationwide were estimated to be
      approximately 50%. We studied the effectiveness of the vaccine in a real-world
      setting outside of a clinical trial. All children presenting to The Children's
      Hospital of Philadelphia with acute gastroenteritis have been monitored for the
      presence of rotavirus antigen in the stool by enzyme-linked immunosorbent assay
      (ELISA [followed by genotyping if ELISA positive]) since the 1994-1995 epidemic
      season, presenting a unique opportunity to assess the impact of the recently
      introduced vaccine. The annual number of community-acquired cases over the
      preceding 13 years had approached or exceeded 100, with 271 cases in 2005 to 2006
      and 167 cases in 2006 to 2007. In the 2007-2008 season, only 36 community
      acquired cases were identified, representing an 87% reduction from the same
      period in 2005 to 2006. G3 was the predominant serotype, accounting for 15
      community cases (42%). Our study is limited by its observational design using
      historical comparisons. Nonetheless, the abrupt decline in rotavirus
      gastroenteritis cases during the 2007-2008 season likely resulted from
      vaccination. Because protection rates appeared to have exceeded vaccination
      rates, herd immunity may have contributed to some degree to the effectiveness of
      the vaccine.

PMID- 19158284
TI  - Optimization and validation of a multiplex, electrochemiluminescence-based
      detection assay for the quantitation of immunoglobulin G serotype-specific
      antipneumococcal antibodies in human serum.
AB  - Pneumovax 23 consists of a mixture of highly purified capsular polysaccharides
      (Ps) from 23 of the most prevalent serotypes of Streptococcus pneumoniae. Testing
      of vaccine immunogenicity has been historically performed on the enzyme-linked
      immunosorbent assay (ELISA) platform, validated to measure immunoglobulin G (IgG)
      antibodies to all 23 serotypes included in Pneumovax 23. In order to
      significantly improve the throughput of this form of testing, we have developed
      and validated a direct binding electrochemiluminescence (ECL)-based multiplex
      assay that can measure the antibody response in human serum to eight serotypes
      within a single microtiter well. The pneumococcal (Pn) ECL assay is based on the
      Meso Scale Discovery (MSD) technology which utilizes a Sulfo-Tag-labeled anti
      human IgG antibody that emits light upon electrochemical stimulation. The Pn ECL
      assay exhibits a wide dynamic range and provides the ability to read
      concentrations down to the minimum reported concentration in the Merck ELISA (0.1
      microg/ml). Cross-reactivity assessment using type-specific monoclonal antibodies
      showed no cross talk between antigen spots within a well. By use of the WHO Pn
      sample reference panel, the results obtained with the Pn ECL assay were compared
      to the results obtained with the international Pn ELISA. The results for the Pn
      ECL assay satisfied the WHO-recommended acceptance criterion for concordance for
      all seven serotypes with published Pn ELISA values, and the overall correlation
      (r value) across the seven serotypes was 0.994. The MSD methodology has great
      potential to be extremely useful for simultaneously quantitating IgG responses to
      several Pn serotypes while conserving serum volumes and laboratory testing time.

PMID- 19158285
TI  - Tracking an invisible target reveals spatial tuning of neurons in the rostral
      superior colliculus is not dependent on visual stimuli.

PMID- 19158286
TI  - Monkey supplementary eye field neurons signal the ordinal position of both
      actions and objects.
AB  - When a monkey executes a learned series of eye movements (for example, rightward
      followed by upward followed by leftward), neurons in the supplementary eye field
      (SEF) fire differentially in conjunction with the first, second, and third
      movements. It has not been clear whether such ordinal position signals are truly
      general, accompanying all forms of sequential behavior, or accompany only learned
      sequences of movements. To resolve this issue, we trained monkeys to perform both
      a serial action task (making saccades in a fixed sequence of directions) and a
      serial object task (making saccades to a fixed sequence of objects). We found
      concordant ordinal position selectivity in the two tasks. Neuronal selectivity
      for the passage of time and expectation of reward could not explain such
      concordance. We conclude that SEF neurons signal ordinal position consistently
      across different task contexts. These signals presumably underlie the ability of
      primates including humans to perform a broad range of serial order tasks.

PMID- 19158287
TI  - HCN1 channel subunits are a molecular substrate for hypnotic actions of ketamine.
AB  - Ketamine has important anesthetic, analgesic, and psychotropic actions. It is
      widely believed that NMDA receptor inhibition accounts for ketamine actions, but
      there remains a dearth of behavioral evidence to support this hypothesis. Here,
      we present an alternative, behaviorally relevant molecular substrate for
      anesthetic effects of ketamine: the HCN1 pacemaker channels that underlie a
      neuronal hyperpolarization-activated cationic current (I(h)). Ketamine caused
      subunit-specific inhibition of recombinant HCN1-containing channels and neuronal
      I(h) at clinically relevant concentrations; the channels were more potently
      inhibited by S-(+)-ketamine than racemic ketamine, consistent with anesthetic
      actions of the compounds. In cortical pyramidal neurons from wild-type, but not
      HCN1 knock-out mice, ketamine induced membrane hyperpolarization and enhanced
      dendritosomatic synaptic coupling; both effects are known to promote cortical
      synchronization and support slow cortical rhythms, like those accompanying
      anesthetic-induced hypnosis. Accordingly, we found that the potency for ketamine
      to provoke a loss-of-righting reflex, a behavioral correlate of hypnosis, was
      strongly reduced in HCN1 knock-out mice. In addition, hypnotic sensitivity to two
      other intravenous anesthetics in HCN1 knock-out mice matched effects on HCN1
      channels; propofol selectively inhibited HCN1 channels and propofol sensitivity
      was diminished in HCN1 knock-out mice, whereas etomidate had no effect on HCN1
      channels and hypnotic sensitivity to etomidate was unaffected by HCN1 gene
      deletion. These data advance HCN1 channels as a novel molecular target for
      ketamine, provide a plausible neuronal mechanism for enhanced cortical
      synchronization during anesthetic-induced hypnosis and suggest that HCN1 channels
      might contribute to other unexplained actions of ketamine.

PMID- 19158288
TI  - Dysregulation of iron homeostasis in the CNS contributes to disease progression
      in a mouse model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS), characterized by degeneration of spinal
      motor neurons, consists of sporadic and familial forms. One cause of familial ALS
      is missense mutations in the superoxide dismutase 1 (SOD1) gene. Iron
      accumulation occurs in the CNS of both forms of ALS; however, its contribution to
      the pathogenesis of ALS is not known. We examined the role of iron in a
      transgenic mouse line overexpressing the human SOD1(G37R) mutant. We show that
      multiple mechanisms may underlie the iron accumulation in neurons and glia in
      SOD1(G37R) transgenic mice. These include dysregulation of proteins involved in
      iron influx and sensing of intracellular iron; iron accumulation in ventral motor
      neurons secondary to blockage of anterograde axonal transport; and increased
      mitochondrial iron load in neurons and glia. We also show that treatment of
      SOD1(G37R) mice with an iron chelator extends life span by 5 weeks, accompanied
      by increased survival of spinal motor neurons and improved locomotor function.
      These data suggest that iron chelator therapy might be useful for the treatment
      of ALS.

PMID- 19158289
TI  - Long-term homeostasis of extracellular glutamate in the rat cerebral cortex
      across sleep and waking states.
AB  - Neuronal firing patterns, neuromodulators, and cerebral metabolism change across
      sleep-waking states, and the synaptic release of glutamate is critically involved
      in these processes. Extrasynaptic glutamate can also affect neural function and
      may be neurotoxic, but whether and how extracellular glutamate is regulated
      across sleep-waking states is unclear. To assess the effect of behavioral state
      on extracellular glutamate at high temporal resolution, we recorded glutamate
      concentration in prefrontal and motor cortex using fixed-potential amperometry in
      freely behaving rats. Simultaneously, we recorded local field potentials (LFPs)
      and electroencephalograms (EEGs) from contralateral cortex. We observed dynamic,
      progressive changes in the concentration of glutamate that switched direction as
      a function of behavioral state. Specifically, the concentration of glutamate
      increased progressively during waking (0.329 +/- 0.06%/min) and rapid eye
      movement (REM) sleep (0.349 +/- 0.13%/min). This increase was opposed by a
      progressive decrease during non-REM (NREM) sleep (0.338 +/- 0.06%/min). During a
      3 h sleep deprivation period, glutamate concentrations initially exhibited the
      progressive rise observed during spontaneous waking. As sleep pressure increased,
      glutamate concentrations ceased to increase and began decreasing despite
      continuous waking. During NREM sleep, the rate of decrease in glutamate was
      positively correlated with sleep intensity, as indexed by LFP slow-wave activity.
      The rate of decrease doubled during recovery sleep after sleep deprivation. Thus,
      the progressive increase in cortical extrasynaptic glutamate during EEG-activated
      states is counteracted by a decrease during NREM sleep that is modulated by sleep
      pressure. These results provide evidence for a long-term homeostasis of
      extracellular glutamate across sleep-waking states.

PMID- 19158290
TI  - Axonal protective effects of the myelin-associated glycoprotein.
AB  - Progressive axonal degeneration follows demyelination in many neurological
      diseases, including multiple sclerosis and inherited demyelinating neuropathies,
      such as Charcot-Marie-Tooth disease. One glial molecule, the myelin-associated
      glycoprotein (MAG), located in the adaxonal plasmalemma of myelin-producing
      cells, is known to signal to the axon and to modulate axonal caliber through
      phosphorylation of axonal neurofilament proteins. This report establishes for the
      first time that MAG also promotes resistance to axonal injury and prevents axonal
      degeneration both in cell culture and in vivo. This effect on axonal stability
      depends on the RGD domain around arginine 118 in the extracellular portion of
      MAG, but it is independent of Nogo signaling in the axon. Exploiting this pathway
      may lead to therapeutic strategies for neurological diseases characterized by
      axonal loss.

PMID- 19158291
TI  - Protein synthesis in distal axons is not required for growth cone responses to
      guidance cues.
AB  - Recent evidence suggests that growth cone responses to guidance cues require
      local protein synthesis. Using chick neurons, we investigated whether protein
      synthesis is required for growth cones of several types to respond to guidance
      cues. First, we found that global inhibition of protein synthesis stops axonal
      elongation after 2 h. When protein synthesis inhibitors were added 15 min before
      adding guidance cues, we found no changes in the typical responses of retinal,
      sensory, and sympathetic growth cones. In the presence of cycloheximide or
      anisomycin, ephrin-A2, slit-3, and semaphorin3A still induced growth cone
      collapse and loss of actin filaments, nerve growth factor (NGF) and neurotrophin
      3 still induced growth cone protrusion and increased filamentous actin, and
      sensory growth cones turned toward an NGF source. In compartmented chambers that
      separated perikarya from axons, axons grew for 24-48 h in the presence of
      cycloheximide and responded to negative and positive cues. Our results indicate
      that protein synthesis is not strictly required in the mechanisms for growth cone
      responses to many guidance cues. Differences between our results and other
      studies may exist because of different cellular metabolic levels in in vitro
      conditions and a difference in when axonal functions become dependent on local
      protein synthesis.

PMID- 19158292
TI  - Non-nuclear Wld(S) determines its neuroprotective efficacy for axons and synapses
      in vivo.
AB  - Axon degeneration contributes widely to neurodegenerative disease but its
      regulation is poorly understood. The Wallerian degeneration slow (Wld(S)) protein
      protects axons dose-dependently in many circumstances but is paradoxically
      abundant in nuclei. To test the hypothesis that Wld(S) acts within nuclei in
      vivo, we redistributed it from nucleus to cytoplasm in transgenic mice.
      Surprisingly, instead of weakening the phenotype as expected, extranuclear Wld(S)
      significantly enhanced structural and functional preservation of transected
      distal axons and their synapses. In contrast to native Wld(S) mutants, distal
      axon stumps remained continuous and ultrastructurally intact up to 7 weeks after
      injury and motor nerve terminals were robustly preserved even in older mice,
      remaining functional for 6 d. Moreover, we detect extranuclear Wld(S) for the
      first time in vivo, and higher axoplasmic levels in transgenic mice with Wld(S)
      redistribution. Cytoplasmic Wld(S) fractionated predominantly with mitochondria
      and microsomes. We conclude that Wld(S) can act in one or more non-nuclear
      compartments to protect axons and synapses, and that molecular changes can
      enhance its therapeutic potential.

PMID- 19158293
TI  - Decreased NR2B subunit synaptic levels cause impaired long-term potentiation but
      not long-term depression.
AB  - The discovery of the molecular mechanisms regulating the abundance of synaptic
      NMDA receptors is essential for understanding how synaptic plasticity, as well as
      excitotoxic events, are regulated. However, a complete understanding of the
      precise molecular mechanisms regulating the composition of the NMDA receptor
      complex at hippocampal synapse is still missing. Here, we show that 2 h of CaMKII
      inhibition leads to a specific reduction of synaptic NR2B-containing NMDA
      receptors without affecting localization of the NR2A subunit; this molecular
      event is accompanied by a dramatic reduction in the induction of long-term
      potentiation (LTP), while long-term depression induction is unaffected. The same
      molecular and functional results were obtained by disrupting NR2B/PSD-95 complex
      with NR2B C-tail cell permeable peptide (TAT-2B). These data indicate that NR2B
      redistribution between synaptic and extrasynaptic membranes represents an
      important molecular disturbance of the glutamatergic synapse and affects the
      correct induction of LTP.

PMID- 19158294
TI  - Endogenous truncated TrkB.T1 receptor regulates neuronal complexity and TrkB
      kinase receptor function in vivo.
AB  - Pathological or in vitro overexpression of the truncated TrkB (TrkB.T1) receptor
      inhibits signaling through the full-length TrkB (TrkB.FL) tyrosine kinase
      receptor. However, to date, the role of endogenous TrkB.T1 is still unknown. By
      studying mice lacking the truncated TrkB.T1 isoform but retaining normal
      spatiotemporal expression of TrkB.FL, we have analyzed TrkB.T1-specific
      physiological functions and its effect on endogenous TrkB kinase signaling in
      vivo. We found that TrkB.T1-deficient mice develop normally but show increased
      anxiety in association with morphological abnormalities in the length and
      complexity of neurites of neurons in the basolateral amygdala. However, no
      behavioral abnormalities were detected in hippocampal-dependent memory tasks,
      which correlated with lack of any obvious hippocampal morphological deficits or
      alterations in basal synaptic transmission and long-term potentiation. In vivo
      reduction of TrkB signaling by removal of one BDNF allele could be partially
      rescued by TrkB.T1 deletion, which was revealed by an amelioration of the
      enhanced aggression and weight gain associated with BDNF haploinsufficiency. Our
      results suggest that, at the physiological level, TrkB.T1 receptors are important
      regulators of TrkB.FL signaling in vivo. Moreover, TrkB.T1 selectively affects
      dendrite complexity of certain neuronal populations.

PMID- 19158295
TI  - Low-threshold primary afferent drive onto GABAergic interneurons in the
      superficial dorsal horn of the mouse.
AB  - Inhibition in the spinal cord dorsal horn is crucial for maintaining separation
      of touch and pain modalities. Disruption of this inhibition results in allodynia,
      allowing low-threshold drive onto pain and temperature-sensitive projection
      neurons. This low-threshold (LT) excitatory pathway is normally under strong
      inhibition. We hypothesized that superficial dorsal horn inhibitory neurons,
      which would be ideally located to suppress LT drive onto projection neurons in a
      feedforward manner, are driven by LT input. In addition, because disinhibition
      induced allodynia shares some features with the immature dorsal horn such as
      elevated sensitivity to LT input, we also questioned whether LT drive onto
      inhibitory neurons changes during postnatal maturation. To investigate these
      questions, slices were made at different ages from transgenic mice with enhanced
      green fluorescent protein expression in GABAergic neurons and whole-cell
      recordings were made from these fluorescent neurons. Evoked synaptic activity was
      measured in response to electrical stimulation of the dorsal root. We demonstrate
      that Abeta fibers activate a significant proportion of superficial dorsal horn
      GABAergic neurons. This occurs with similar excitatory synaptic drive throughout
      postnatal maturation, but with a greater prevalence at younger ages. These
      GABAergic neurons are well situated to contribute to suppressing LT activation of
      output projection neurons. In addition, the majority of these GABAergic neurons
      also had convergent input from high-threshold fibers, suggesting that this novel
      subclass of GABAergic neurons is important for gating innocuous as well as
      noxious information.

PMID- 19158296
TI  - The basolateral amygdala is critical to the expression of pavlovian and
      instrumental outcome-specific reinforcer devaluation effects.
AB  - Considerable evidence implicates the basolateral amygdala (BLA) in the formation
      of outcome representations that link cues to the incentive properties of
      reinforcers. Animals with BLA damage show impaired performance in reinforcer
      devaluation tasks, in which the value of the food reinforcer is reduced by
      satiation or food-toxin pairings after the completion of cue or response
      training. Although intact animals spontaneously reduce their conditioned
      responding after such reinforcer devaluation procedures, animals with BLA lesions
      made before training typically do not, as evidenced across a range of species,
      training contingencies, and devaluation procedures. In contrast, the role of the
      BLA in devaluation task performance once such outcome representations are
      established is unclear. Whereas Pickens et al. (2003) found normal devaluation
      performance in rats when BLA lesions were made after pavlovian light-food
      pairings but before devaluation by food-toxin pairings, Ostlund and Balleine
      (2008) found impaired devaluation performance when BLA lesions were made after
      instrumental training with multiple instrumental responses and food reinforcers
      but before devaluation of one reinforcer by selective satiation. Those studies
      differed in their use of pavlovian or operant training contingencies, single or
      multiple reinforcers, and associative or motivational devaluation procedures.
      Here we found that, when multiple reinforcers were used, posttraining BLA lesions
      disrupted the expression of devaluation performance in rats, using either
      pavlovian or instrumental training procedures and either conditioned taste
      aversion or satiation devaluation procedures. Thus, BLA apparently plays a
      critical role in maintaining or using sensory associations of reinforcer value
      when multiple outcomes must be coded but not under single-outcome conditions.

PMID- 19158297
TI  - Mood influences supraspinal pain processing separately from attention.
AB  - Studies show that inducing a positive mood or diverting attention from pain
      decreases pain perception. Nevertheless, induction manipulations, such as viewing
      interesting movies or performing mathematical tasks, often influence both
      emotional and attentional states. Imaging studies have examined the neural basis
      of psychological pain modulation, but none has explicitly separated the effects
      of emotion and attention. Using odors to modulate mood and shift attention from
      pain, we previously showed that the perceptual consequences of changing mood
      differed from those of altering attention, with mood primarily altering pain
      unpleasantness and attention preferentially altering pain intensity. These
      findings suggest that brain circuits involved in pain modulation provoked by mood
      or attention are partially separable. Here we used functional magnetic resonance
      imaging to directly compare the neurocircuitry involved in mood- and attention
      related pain modulation. We manipulated independently mood state and attention
      direction, using tasks involving heat pain and pleasant and unpleasant odors.
      Pleasant odors, independent of attentional focus, induced positive mood changes
      and decreased pain unpleasantness and pain-related activity within the anterior
      cingulate (ACC), medial thalamus, and primary and secondary somatosensory
      cortices. The effects of attentional state were less robust, with only the
      activity in anterior insular cortex (aIC) showing possible attentional
      modulation. Lateral inferior frontal cortex [LinfF; Brodmann's area (BA) 45/47]
      activity correlated with mood-related modulation, whereas superior posterior
      parietal (SPP; BA7) and entorhinal activity correlated with attention-related
      modulation. ACC activity covaried with LinfF and periacqueductal gray activity,
      whereas aIC activity covaried with SPP activity. These findings suggest that
      separate neuromodulatory circuits underlie emotional and attentional modulation
      of pain.

PMID- 19158298
TI  - Calcium current diversity in physiologically different local interneuron types of
      the antennal lobe.
AB  - Behavioral and physiological studies show that neuronal interactions among the
      glomeruli in the insect antennal lobe (AL) take place during the processing of
      odor information. These interactions are mediated by a complex network of
      inhibitory and excitatory local interneurons (LNs) that restructure the olfactory
      representation in the AL, thereby regulating the tuning profile of projection
      neurons. In Periplaneta americana, we characterized two LN types with distinctive
      physiological properties: (1) type I LNs that generated Na(+)-driven action
      potentials on odor stimulation and exhibited GABA-like immunoreactivity (GLIR)
      and (2) type II LNs, in which odor stimulation evoked depolarizations, but no
      Na(+)-driven action potentials (APs). Type II LNs did not express voltage
      dependent transient Na(+) currents and accordingly would not trigger transmitter
      release by Na(+)-driven APs. Ninety percent of type II LNs did not exhibit GLIR.
      The distinct intrinsic firing properties were reflected in functional parameters
      of their voltage-activated Ca(2+) currents (I(Ca)). Consistent with graded
      synaptic release, we found a shift in the voltage for half-maximal activation of
      I(Ca) to more hyperpolarized membrane potentials in the type II LNs. These marked
      physiological differences between the two LN types imply consequences for their
      computational capacity, synaptic output kinetics, and thus their function in the
      olfactory circuit.

PMID- 19158299
TI  - The processing of three-dimensional shape from disparity in the human brain.
AB  - Three-dimensional (3D) shape is important for the visual control of grasping and
      manipulation and for object recognition. Although there has been some progress in
      our understanding of how 3D shape is extracted from motion and other monocular
      cues, little is known of how the human brain extracts 3D shape from disparity,
      commonly regarded as the strongest depth cue. Previous fMRI studies in the awake
      monkey have established that the interaction between stereo (present or absent)
      and the order of disparity (zero or second order) constitutes the MR signature of
      regions housing second-order disparity-selective neurons (Janssen et al., 2000;
      Srivastava et al., 2006; Durand et al., 2007; Joly et al., 2007). Testing the
      interaction between stereo and order of disparity in a large cohort of human
      subjects, revealed the involvement of five IPS regions (VIPS/V7*, POIPS, DIPSM,
      DIPSA, and phAIP), as well as V3 and the V3A complex in occipital cortex, the
      posterior inferior temporal gyrus (ITG), and ventral premotor cortex (vPrCS) in
      the extraction and processing of 3D shape from stereo. Control experiments ruled
      out attention and convergence eye movements as confounding factors. Many of these
      regions, DIPSM, DIPSA, phAIP, and probably posterior ITG and ventral premotor
      cortex, correspond to monkey regions with similar functionality, whereas the
      evolutionarily new or modified regions are located in occipital (the V3A complex)
      and occipitoparietal cortex (VIPS/V7* and POIPS). Interestingly, activity in
      these occipital regions correlates with the depth amplitude perceived by the
      subjects in the 3D surfaces used as stimuli in these fMRI experiments.

PMID- 19158301
TI  - Depletion of Ly6G/Gr-1 leukocytes after spinal cord injury in mice alters wound
      healing and worsens neurological outcome.
AB  - Spinal cord injury (SCI) induces a robust inflammatory response and the
      extravasation of leukocytes into the injured tissue. To further knowledge of the
      functions of neuroinflammation in SCI in mice, we depleted the early arriving
      neutrophils using an anti-Ly6G/Gr-1 antibody. Complete blood counts revealed that
      neutrophils increased approximately 3-fold over uninjured controls and peaked at
      6-12 h after injury, and that anti-Ly6G/Gr-1 treatment reduced circulating
      neutrophils by >90% at these time points. Intravital and spinning disk confocal
      microscopy of the exposed posterior vein and postcapillary venules showed a
      significant reduction in rolling and adhering neutrophils in vivo after anti
      Ly6G/Gr-1 treatment; this was accompanied by a parallel reduction in neutrophil
      numbers within the injured spinal cord at 24 and 48 h as determined by flow
      cytometry. The evolution of astrocyte reactivity, a wound healing response, was
      reduced in anti-Ly6G/Gr-1-treated mice, which also had less spared white matter
      and axonal preservation compared with isotype controls. These histological
      outcomes may be caused by alterations of growth factors and chemokines important
      in promoting wound healing. Importantly, anti-Ly6G/Gr-1 treatment worsened
      behavioral outcome as determined using the Basso Mouse Scale and subscores.
      Although the spectrum of cells affected by anti-Ly6G/Gr-1 antibody treatment
      cannot be fully ascertained at this point, the correspondence of neutrophil
      depletion and worsened recovery suggests that neutrophils promote recovery after
      SCI through wound healing and protective events that limit lesion propagation.

PMID- 19158300
TI  - TPRV1 expression defines functionally distinct pelvic colon afferents.
AB  - Changes in primary sensory neurons are likely to contribute to the emergence of
      chronic visceral pain. An important step in understanding visceral pain is the
      development of comprehensive phenotypes that combines functional and anatomical
      properties for these neurons. We developed a novel ex vivo physiology preparation
      in mice that allows intracellular recording from colon sensory neurons during
      colon distension, in the presence and absence of pharmacologic agents. This
      preparation also allows recovery of functionally characterized afferents for
      histochemical analysis. Recordings obtained from L6 dorsal root ganglion cells in
      C57BL/6 mice identified two distinct populations of distension-responsive colon
      afferents: high-firing frequency (HF) and low-firing frequency (LF) cells. Fluid
      distension of the colon elicited rapid firing (>20 Hz) in HF cells, whereas LF
      cells seldom fired >5 Hz. Distension response thresholds were significantly lower
      in HF cells (LF, 17.5 +/- 1.1 cmH(2)O; HF, 2.6 +/- 1.0 cmH(2)O). Responses of
      most LF afferents to colon distension were sensitized by luminal application of
      capsaicin (1 microm; 8 of 9 LF cells), mustard oil (100 microm; 10 of 12 LF
      cells), and low pH (pH 4.0; 5 of 6 LF cells). In contrast, few HF afferents were
      sensitized by capsaicin (3 of 9), mustard oil (2 of 7), or low pH (1 of 6)
      application. Few HF afferents (4 of 23) expressed the capsaicin receptor, TRPV1.
      In contrast, 87% (25 of 29) of LF afferents expressed TRPV1. TRPV1 has been shown
      to be required for development of inflammatory hyperalgesia. These results
      suggest a unique functional role of TRPV1-positive colon afferents that could be
      exploited to design specific therapies for visceral hypersensitivity.

PMID- 19158302
TI  - Encoding of gustatory working memory by orbitofrontal neurons.
AB  - The content model regarding the functional organization of working memory in
      prefrontal cortex (PFC) states that different PFC areas encode different types of
      information in working memory depending on their afferent connections with other
      brain areas. Previous studies that tested this model focused on visual, auditory
      and somatosensory information. However, posterior areas processing this
      information project to widespread and overlapping regions of lateral PFC, making
      it difficult to establish the veracity of the model. In contrast, gustatory
      information enters PFC via orbitofrontal cortex (OFC), and so the content model
      would argue that OFC should be responsible for maintaining gustatory information
      in working memory. To test this, we recorded the activity of single neurons
      throughout PFC and gustatory cortex (GUS) from two subjects while they performed
      a gustatory delayed-match-to-sample task with intervening gustatory distraction.
      Neurons that encoded the identity of the gustatory stimulus across the delay,
      consistent with a role in gustatory working memory, were most prevalent in OFC
      and GUS compared with dorsolateral PFC and ventrolateral PFC. Gustatory
      information in OFC was more resilient to intervening distraction, paralleling
      previous findings regarding visual working memory processes in PFC and posterior
      sensory cortex. Our findings provide support for the content model of working
      memory organization. Maintaining gustatory information may be one aspect of a
      wider function for OFC in reward working memory that could contribute to its role
      in decision-making.

PMID- 19158303
TI  - Insulin-like growth factor-1 promotes G(1)/S cell cycle progression through
      bidirectional regulation of cyclins and cyclin-dependent kinase inhibitors via
      the phosphatidylinositol 3-kinase/Akt pathway in developing rat cerebral cortex.
AB  - Although survival-promoting effects of insulin-like growth factor-1 (IGF-1)
      during neurogenesis are well characterized, mitogenic effects remain less well
      substantiated. Here, we characterize cell cycle regulators and signaling pathways
      underlying IGF-1 effects on embryonic cortical precursor proliferation in vitro
      and in vivo. In vitro, IGF-1 stimulated cell cycle progression and increased cell
      number without promoting cell survival. IGF-1 induced rapid increases in cyclin
      D1 and D3 protein levels at 4 h and cyclin E at 8 h. Moreover, p27(KIP1) and
      p57(KIP2) expression were reduced, suggesting downregulation of negative
      regulators contributes to mitogenesis. Furthermore, the phosphatidylinositol 3
      kinase (PI3K)/Akt pathway specifically underlies IGF-1 activity, because blocking
      this pathway, but not MEK (mitogen-activated protein kinase kinase)/ERK
      (extracellular signal-regulated kinase), prevented mitogenesis. To determine
      whether mechanisms defined in culture relate to corticogenesis in vivo, we
      performed transuterine intracerebroventricular injections. Whereas blockade of
      endogenous factor with anti-IGF-1 antibody decreased DNA synthesis, IGF-1
      injection stimulated DNA synthesis and increased the number of S-phase cells in
      the ventricular zone. IGF-1 treatment increased phospho-Akt fourfold at 30 min,
      cyclins D1 and E by 6 h, and decreased p27(KIP1) and p57(KIP2) expression.
      Moreover, blockade of the PI3K/Akt pathway in vivo decreased DNA synthesis and
      cyclin E, increased p27(KIP1) and p57(KIP2) expression, and prevented IGF-1
      induced cyclin E mRNA upregulation. Finally, IGF-1 injection in embryos increased
      postnatal day 10 brain DNA content by 28%, suggesting a role for IGF-1 in brain
      growth control. These results demonstrate a mitogenic role for IGF-1 that tightly
      controls both positive and negative cell cycle regulators, and indicate that the
      PI3K/Akt pathway mediates IGF-1 mitogenic signaling during corticogenesis.

PMID- 19158304
TI  - Receptive fields of retinal bipolar cells are mediated by heterogeneous synaptic
      circuitry.
AB  - Center-surround antagonistic receptive field (CSARF) organization is the basic
      synaptic circuit that serves as elementary building blocks for spatial
      information processing in the visual system. Cells with such receptive fields
      converge into higher-order visual neurons to form more complex receptive fields.
      Retinal bipolar cells (BCs) are the first neurons along the visual pathway that
      exhibit CSARF organization. BCs have been classified according to their response
      polarities and rod/cone inputs, and they project signals to target cells at
      different sublaminae of the inner plexiform layer. On the other hand, CSARFs of
      various types of BCs have been assumed be organized the same way. Here we
      examined center and surround responses of over 250 salamander BCs, and
      demonstrated that different types of BCs exhibit different patterns of dye
      coupling, receptive field center size, surround response strength, and
      conductance changes associated with center and surround responses. We show that
      BC receptive field center sizes varied with the degree of BC-BC coupling, and
      that surround responses of different BCs are mediated by different combinations
      of five lateral synaptic pathways mediated by the horizontal cells and amacrine
      cells. The finding of heterogeneous receptive field circuitry fundamentally
      challenges the common assumption that CSARFs of different subtypes of visual
      neurons are mediated by the same synaptic pathways. BCs carrying different visual
      signals use different synaptic circuits to process spatial information, allowing
      shape and contrast computation be differentially modulated by various lighting
      and adaptation conditions.

PMID- 19158305
TI  - Propagation of sinusoidal electrical waves along the spinal cord during a fictive
      motor task.
AB  - We present for the first time direct electrophysiological evidence of the
      phenomenon of traveling electrical waves produced by populations of interneurons
      within the spinal cord. We show that, during a fictive rhythmic motor task,
      scratching, an electrical field potential of spinal interneurons takes the shape
      of a sinuous wave, "sweeping" the lumbosacral spinal cord rostrocaudally with a
      mean speed of approximately 0.3 m/s. We observed that traveling waves and
      scratching have the same cycle duration and that duration of the flexor phase,
      but not of the extensor phase, is highly correlated with the cycle duration of
      the traveling waves. Furthermore, we found that the interneurons from the deep
      dorsal horn and the intermediate nucleus can generate the spinal traveling waves,
      even in the absence of motoneuronal activity. These findings show that the
      sinusoidal field potentials generated during fictive scratching could be a
      powerful tool to disclose the organization of central pattern generator networks.

PMID- 19158306
TI  - Spatiotemporal patterns of cortical activity with bilateral cochlear implants in
      congenital deafness.
AB  - Congenital deafness affects developmental processes in the auditory cortex. In
      this study, local field potentials (LFPs) were mapped at the cortical surface
      with microelectrodes in response to cochlear implant stimulation. LFPs were
      compared between hearing controls and congenitally deaf cats (CDCs). Pulsatile
      electrical stimulation initially evoked cortical activity in the rostral parts of
      the primary auditory field (A1). This progressed both in the approximate
      dorsoventral direction (along the isofrequency stripe) and in the rostrocaudal
      direction. The dorsal branch of the wavefront split into a caudal branch
      (propagating in A1) and another smaller one propagating rostrally into the AAF
      (anterior auditory field). After the front reached the caudal border of A1, a
      "reflection wave" appeared, propagating back rostrally. In total, the waves took
      approximately 13-15 ms to propagate along A1 and return back. In CDCs, the
      propagation pattern was significantly disturbed, with a more synchronous
      activation of distant cortical regions. The maps obtained from contralateral and
      ipsilateral stimulation overlapped in both groups of animals. Although controls
      showed differences in the latency-amplitude patterns, cortical waves evoked by
      contralateral and ipsilateral stimulation were more similar in CDCs.
      Additionally, in controls, LFPs with contralateral and ipsilateral stimulation
      were more similar in caudal A1 than in rostral A1. This dichotomy was lost in
      deaf animals. In conclusion, propagating cortical waves are specific for the
      contralateral ear, they are affected by auditory deprivation, and the specificity
      of the cortex for stimulation of the contralateral ear is reduced by deprivation.

PMID- 19158309
TI  - Distinctive neuronal networks and biochemical pathways for appetitive and
      aversive memory in Drosophila larvae.
AB  - Associative strength between conditioned stimulus (CS) and unconditioned stimulus
      (US) is thought to determine learning efficacy in classical conditioning.
      Elucidation of the neuronal mechanism that underlies the association between CS
      and US in the brain is thus critical to understand the principle of memory
      formation. With a simple brain organization, the Drosophila larva provides an
      attractive model system to investigate learning at the neurocircuitry level.
      Previously, we described a single-odor paradigm for larval associative learning
      using sucrose as a reward, and showed that larval appetitive memory lasts longer
      than 2 h. In this work, we describe behavioral and genetic characterization of
      larval aversive olfactory memory formed in our paradigm, and compare its
      stability and neurocircuitry with those of appetitive memory. Despite identical
      training paradigms, larval olfactory memory formed with quinine or NaCl is short
      lived to be lost in 20 min. As with appetitive memory, larval aversive memory
      produced in this paradigm depends on intact cAMP signaling, but neither mutation
      of amnesiac nor suppression of CREB activity affects its kinetics. Neurocircuitry
      analyses suggest that aversive memory is stored before the presynaptic termini of
      the larval mushroom body neurons as is the case with appetitive memory. However,
      synaptic output of octopaminergic and dopaminergic neurons, which exhibit
      distinctive innervation patterns on the larval mushroom body and antennal lobe,
      is differentially required for the acquisition of appetitive and aversive memory,
      respectively. These results as a whole suggest that the genetically programmed
      memory circuitries might provide predisposition in the efficacy of inducing
      longer-lived memory components in associative learning.

PMID- 19158308
TI  - Impaired synaptic vesicle release and immaturity of neuromuscular junctions in
      spinal muscular atrophy mice.
AB  - The motor neuron disease spinal muscular atrophy (SMA) causes profound muscle
      weakness that most often leads to early death. At autopsy, SMA is characterized
      by loss of motor neurons and muscle atrophy, but the initial cellular events that
      precipitate motor unit dysfunction and loss remain poorly characterized. Here, we
      examined the function and corresponding structure of neuromuscular junction (NMJ)
      synapses in a mouse model of severe SMA (hSMN2/delta7SMN/mSmn-/-). Surprisingly,
      most SMA NMJs remained innervated even late in the disease course; however they
      showed abnormal synaptic transmission. There was a two-fold reduction in the
      amplitudes of the evoked endplate currents (EPCs), but normal spontaneous
      miniature EPC (MEPC) amplitudes. These features in combination indicate reduced
      quantal content. SMA NMJs also demonstrated increased facilitation suggesting a
      reduced probability of vesicle release. By electron microscopy, we found a
      decreased density of synaptic vesicles that is likely to contribute to the
      reduced release probability. In addition to presynaptic defects, there were
      postsynaptic abnormalities. EPC and MEPC decay time constants were prolonged
      because of a slowed switch from the fetal acetylcholine receptor (AChR) gamma
      subunit to the adult epsilon-subunit. There was also reduced size of AChR
      clusters and small myofibers, which expressed an immature pattern of myosin heavy
      chains. Together these results indicate that impaired synaptic vesicle release at
      NMJs in severe SMA is likely to contribute to failed postnatal maturation of
      motor units and muscle weakness.

PMID- 19158307
TI  - Photoreceptor neurons find new synaptic targets when misdirected by
      overexpressing runt in Drosophila.
AB  - As a neuron differentiates, it adopts a suite of features specific to its
      particular type. Fly photoreceptors are of two types: R1-R6, which innervate the
      first optic neuropile, the lamina; and R7-R8, which innervate the second, the
      medulla. Photoreceptors R1-R6 normally have large light-absorbing rhabdomeres,
      express Rhodopsin1, and have synaptic terminals that innervate the lamina. In
      Drosophila melanogaster, we used the yeast GAL4/UAS system to drive exogenous
      expression of the transcription factor Runt in subsets of photoreceptors,
      resulting in aberrant axonal pathfinding and, ultimately, incorrect targeting of
      R1-R6 synaptic terminals to the medulla, normally occupied by terminals from R7
      and R8. Even when subsets of their normal R1-R6 photoreceptor inputs penetrate
      the lamina, to terminate in the medulla, normal target cells within the lamina
      persist and maintain expression of cell-specific markers. Some R1-R6
      photoreceptors form reciprocal synaptic inputs with their normal lamina targets,
      whereas supernumerary terminals targeted to the medulla also form synapses. At
      both sites, tetrad synapses form, with four postsynaptic elements at each release
      site, the usual number in the lamina. In addition, the terminals at both sites
      are invaginated by profiles of glia, at organelles called capitate projections,
      which in the lamina are photoreceptor sites of vesicle endocytosis. The size and
      shape of the capitate projection heads are identical at both lamina and medulla
      sites, although those in the medulla are ectopic and receive invaginations from
      foreign glia. This uniformity indicates the cell-autonomous determination of the
      architecture of its synaptic organelles by the presynaptic photoreceptor
      terminal.

PMID- 19158310
TI  - F-actin and myosin II accelerate catecholamine release from chromaffin granules.
AB  - The roles of nonmuscle myosin II and cortical actin filaments in chromaffin
      granule exocytosis were studied by confocal fluorescence microscopy, amperometry,
      and cell-attached capacitance measurements. Fluorescence imaging indicated
      decreased mobility of granules near the plasma membrane following inhibition of
      myosin II function with blebbistatin. Slower fusion pore expansion rates and
      longer fusion pore lifetimes were observed after inhibition of actin
      polymerization using cytochalasin D. Amperometric recordings revealed increased
      amperometric spike half-widths without change in quantal size after either myosin
      II inhibition or actin disruption. These results suggest that actin and myosin II
      facilitate release from individual chromaffin granules by accelerating
      dissociation of catecholamines from the intragranular matrix possibly through
      generation of mechanical forces.

PMID- 19158311
TI  - Adenosine A(1) and A(2A) receptors in mouse prefrontal cortex modulate
      acetylcholine release and behavioral arousal.
AB  - During prolonged intervals of wakefulness, brain adenosine levels rise within the
      basal forebrain and cortex. The view that adenosine promotes sleep is supported
      by the corollary that N-methylated xanthines such as caffeine increase brain and
      behavioral arousal by blocking adenosine receptors. The four subtypes of
      adenosine receptors are distributed heterogeneously throughout the brain, yet the
      neurotransmitter systems and brain regions through which adenosine receptor
      blockade causes arousal are incompletely understood. This study tested the
      hypothesis that adenosine A(1) and A(2A) receptors in the prefrontal cortex
      contribute to the regulation of behavioral and cortical arousal. Dependent
      measures included acetylcholine (ACh) release in the prefrontal cortex, cortical
      electroencephalographic (EEG) power, and time to waking after anesthesia. Sleep
      and wakefulness were also quantified after microinjecting an adenosine A(1)
      receptor antagonist into the prefrontal cortex. The results showed that adenosine
      A(1) and A(2A) receptors in the prefrontal cortex modulate cortical ACh release,
      behavioral arousal, EEG delta power, and sleep. Additional dual microdialysis
      studies revealed that ACh release in the pontine reticular formation is
      significantly altered by dialysis delivery of adenosine receptor agonists and
      antagonists to the prefrontal cortex. These data, and early brain transection
      studies demonstrating that the forebrain is not needed for sleep cycle
      generation, suggest that the prefrontal cortex modulates EEG and behavioral
      arousal via descending input to the pontine brainstem. The results provide novel
      evidence that adenosine A(1) receptors within the prefrontal cortex comprise part
      of a descending system that inhibits wakefulness.

PMID- 19158312
TI  - Two novel CYP2D6*10 haplotypes as possible causes of a poor metabolic phenotype
      in Japanese.
AB  - During the course of sequencing for the CYP2D6 gene, we found a novel single
      nucleotide polymorphism of g.3318G>A (E383K) associated with CYP2D6*10, termed as
      CYP2D6*72. We also found a g.1611T>A (F120I) in the CYP2D6*49, which was
      previously identified as a CYP2D6*10-associated allele in an independent Japanese
      population. To clarify the effects of these novel CYP2D6*10 haplotypes on the
      functions of CYP2D6, kinetic analysis for dextromethorphan O-demethylation was
      performed using the Escherichia coli expression system and human liver
      microsomes. The V(max)/K(m) values for dextromethorphan O-demethylation catalyzed
      by recombinant CYP2D6 forms encoded by CYP2D6*10, CYP2D6*49, and CYP2D6*72 were
      3.0, 0.5, and 1.3%, respectively, compared with that catalyzed by CYP2D6.1. Liver
      microsomes from a human subject genotyped as CYP2D6*10/*49 also showed a reduced
      dextromethorphan O-demethylase activity. CYP2D6.49 formed a 7
      hydroxydextromethorphan, with a roughly similar V(max)/K(m) value to that of O
      demethylation. These results suggest that these two CYP2D6*10 haplotypes are
      possible causes of interindividual variation in the activities and the substrate
      specificity of CYP2D6.

PMID- 19158313
TI  - Human pregnane X receptor activation and CYP3A4/CYP2B6 induction by 2,3
      oxidosqualene:lanosterol cyclase inhibition.
AB  - The effects of [4'-(6-allyl-methyl-amino-hexyloxy)-2'-fluoro-phenyl]-(4
      bromophenyl)-methanone fumarate (Ro 48-8071), an inhibitor of 2,3
      oxidosqualene:lanosterol cyclase (cyclase), were evaluated on CYP3A4 and CYP2B6
      mRNA content in primary cultured human hepatocytes. In seven hepatocyte culture
      preparations, 24-h treatment with 3, 10, or 30 microM Ro 48-8071 produced median
      increases in CYP3A4 mRNA content that were 2.2-, 7.1-, and 8.5-fold greater than
      untreated control, respectively, and produced increases in CYP2B6 mRNA content
      that were 3.0-, 4.6-, and 3.4-fold greater than control, respectively. Increases
      in CYP3A4 immunoreactive protein content were also measured in Ro 48-8071-treated
      hepatocytes. To evaluate the effects of cyclase inhibitor treatments further, a
      pregnane X receptor (PXR)-responsive transactivation assay in HepG2 cells was
      used. Ro 48-8071, trans-N-(4-chlorobenzoyl)-N-methyl-(4
      dimethylaminomethylphenyl)-cyclohexylamine (BIBX 79), and 3beta-(2
      diethylaminoethoxy)androst-5-en-17-one HCl (U18666A) induced luciferase
      expression from a PXR-responsive reporter with EC(50)s of 0.113, 0.916, and 0.294
      microM, respectively. Treatment of the HepG2 system with (E)N-ethyl-N-(6,6
      dimethyl-2-hepten-4-ynyl)-3-[(3,3'-bithiophen-5-yl)methoxy]benzenemethanamine (NB
      598), an inhibitor of squalene monooxygenase, at concentrations sufficient to
      achieve cholesterol biosynthesis inhibition significantly inhibited cyclase
      inhibitor-mediated, but not rifampicin-mediated, reporter induction. Direct
      treatment of the HepG2 system with 1 to 10 microM squalene 2,3:22,23-dioxide, but
      not squalene 2,3-oxide, significantly activated PXR-responsive reporter
      expression. Also, squalene 2,3:22,23-dioxide bound to human PXR in vitro with an
      IC(50) of 3.35 microM. These data indicate that cyclase inhibitors are capable of
      producing CYP3A4 and CYP2B6 induction in primary cultured human hepatocytes, and
      that an endogenous squalene metabolite is a conserved intracrine activator of
      PXR.

PMID- 19158314
TI  - CYP3A4-mediated ester cleavage as the major metabolic pathway of the oral taxane
      3'-tert-butyl-3'-N-tert-butyloxycarbonyl-4-deacetyl-3'-dephenyl-3'-N-debenzoyl-4
      O-methoxycarbonyl-paclitaxel (BMS-275183).
AB  - 3'-tert-Butyl-3'-N-tert-butyloxycarbonyl-4-deacetyl-3'-dephenyl-3'-N-debenzoyl-4
      O-methoxycarbonyl-paclitaxel (BMS-275183) is an orally available taxane analog
      that has the potential to be used as an oral agent to treat cancers. The compound
      is similar to the two clinically intravenously administered taxanes, paclitaxel
      and docetaxel, in that it contains a baccatin ring linked to a side chain through
      an ester bond. Unlike the other taxanes, the hydrolysis of this ester bond leads
      to formation of a free baccatin core (M13) that was the major metabolism pathway
      in incubations of [(14)C]BMS-275183 in human liver microsomes (HLMs) in the
      presence of NADPH, but it was not formed in incubations with human liver cytosol
      or HLM in the absence of NADPH. The other prominent metabolites formed in HLM
      incubations resulted from oxidation of t-butyl groups on the side chain (M20,
      M20B, M21, M22, and M23). All these metabolites were formed by cDNA-expressed
      CYP3A and not by other cytochrome P450 (P450) enzymes tested. Formation of these
      metabolites was selectively inhibited by ketoconazole and troleandomycin. The
      formation of M13 followed Michaelis-Menten kinetics with the K(m) values of 1.3
      to 2.4 muM in HLM or CYP3A4; the V(max) value for the formation of M13 and M23 in
      the cDNA-expressed CYP3A4 matched well (within 2-fold difference) with that
      determined in HLM when expressed in units of per picomole of P450. These results
      showed that BMS-275183 is metabolized by CYP3A4 to yield baccatin through
      oxidation of side-chain t-butyl groups. An intramolecular cyclization of a side
      chain hydroxylation metabolite is proposed to be responsible for the formation of
      M13, the side-chain hydrolysis metabolite.

PMID- 19158315
TI  - Receptor occupancy and brain free fraction.
AB  - This study was designed to investigate whether brain unbound concentration
      (C(u,brain)) is a better predictor of dopamine D(2) receptor occupancy than total
      brain concentration, cerebrospinal fluid concentration (C(CSF)), or blood unbound
      concentration (C(u,blood)). The ex vivo D(2) receptor occupancy and concentration
      time profiles in cerebrospinal fluid, blood, and brain of six marketed
      antipsychotic drugs were determined after oral administration in rats at a range
      of dose levels. The C(u,brain) was estimated from the product of total brain
      concentration and unbound fraction, which was determined using a brain homogenate
      method. In conclusion, the C(u,brain) of selected antipsychotic agents is a good
      predictor of D(2) receptor occupancy in rats. Furthermore, C(u,brain) seems to
      provide a better prediction of D(2) receptor occupancy than C(CSF) or C(u,blood)
      for those compounds whose mechanism of entry into brain tissue is influenced by
      factors other than simple passive diffusion.

PMID- 19158316
TI  - National trends in intimate partner homicides: explaining declines in Canada,
      1976 to 2001.
AB  - In the past decade, research has begun to identify factors that may be
      contributing to declines in spousal homicide. The authors address two gaps in the
      Canadian literature: (a) the documentation of trends, including subgroup
      variations, and (b) the identification of factors that may be associated with
      declines. Using Statistics Canada data, the authors assess the association of
      declines with various factors. Results indicate that shifts in relative
      employment and divorce rates appear to be associated with declining rates for
      women, whereas shifts in men's education and divorce rates appear to be
      associated with declining rates of spousal homicide for men.

PMID- 19158317
TI  - Influence of short-term rosuvastatin therapy on endothelial progenitor cells and
      endothelial function.
AB  - Endothelial progenitor cells maintain endothelium integrity by replacing injured
      endothelial cells. Cholesterol-lowering promotes either endothelial progenitor
      cells mobilization or improves endothelial function. It is unknown whether
      improving endothelial function with statin is associated with a parallel
      increased endothelial progenitor cells availability. Thirty-two
      hypercholesterolemic patients were assigned to 4-week rosuvastatin (10 mg daily)
      and 16 hypercholesterolemic served as controls. Circulating endothelial
      progenitor cells, brachial artery flow-mediated vasodilatation, an index of
      endothelial function, and the lipid profile were measured before and after the 4
      week statin therapy. At baseline, we found a correlation between circulating
      endothelial progenitor cells and flow-mediated vasodilatation (r = .31, P =
      .029). At the end of the 4-week intervention with rosuvastatin there was a 37%
      reduction in low-density lipoprotein cholesterol (P < .001) and a significant 72%
      increase in the number of endothelial progenitor cells and flow-mediated
      vasodilatation (4.7 + 0.7% to 8.8 + 0.4%, P < .001). Endothelial progenitor cells
      and flow-mediated vasodilatation were unchanged at the end of the study in
      patients not taking statin. A correlation emerged between endothelial progenitor
      cells and flow-mediated vasodilatation variations (r = .52, P < .001), this
      correlation being still significant after controlling for blood cholesterol
      reduction. In conclusion, short-term rosuvastatin therapy contributes in
      hyperchoelsterolemic patients to improving endothelial function by lowering
      cholesterol and increasing the number of circulating endothelial progenitor
      cells; the latter effect appears to be partly independent from reduction in
      plasma cholesterol.

PMID- 19158318
TI  - Amino acid transceptors: gate keepers of nutrient exchange and regulators of
      nutrient signaling.
AB  - Amino acid transporters at the surface of cells are in an ideal location to relay
      nutritional information, as well as nutrients themselves, to the cell interior.
      These transporters are able to modulate signaling downstream of intracellular
      amino acid receptors by regulating intracellular amino acid concentrations
      through processes of coupled transport. The concept of dual-function amino acid
      transporter/receptor (or "transceptor") proteins is well established in primitive
      eukaryotes such as yeast, where detection of extracellular amino acid deficiency
      leads to upregulation of proteins involved in biosynthesis and transport of the
      deficient amino acid(s). The evolution of the "extracellular milieu" and nutrient
      regulated endocrine controls in higher eukaryotes, alongside their frequent
      inability to synthesize all proteinaceous amino acids (and, hence, the
      requirement for indispensable amino acids in their diet), appears to have
      lessened the priority of extracellular amino acid sensing as a stimulus for
      metabolic signals. Nevertheless, recent studies of amino acid transporters in
      flies and mammalian cell lines have revealed perhaps unanticipated "echoes" of
      these transceptor functions, which are revealed by cellular stresses (notably
      starvation) or gene modification/silencing. APC-transporter superfamily members,
      including slimfast, path, and SNAT2 all appear capable of sensing and signaling
      amino acid availability to the target of rapamycin (TOR) pathway, possibly
      through PI 3-kinase-dependent mechanisms. We hypothesize (by extrapolation from
      knowledge of the yeast Ssy1 transceptor) that, at least for SNAT2, the
      transceptor discriminates between extracellular and intracellular amino acid
      stimuli when evoking a signal.

PMID- 19158319
TI  - Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD
      rodent models.
AB  - The incidence and prevalence of type 2 diabetes (T2D) continue to escalate at an
      unprecedented rate in the United States, particularly among populations with high
      rates of obesity. The impact of T2D on bone mass, geometry, architecture,
      strength, and resistance to fracture has yet to be incontrovertibly characterized
      because of the complex and heterogeneous nature of this disease. This study
      utilized skeletally mature male diabetic rats of the commonly used Zucker
      diabetic fatty (ZDF) and Zucker diabetic Sprague-Dawley (ZDSD) strains as
      surrogate models to assess alterations in bone attributable to T2D-like states.
      After the animals were euthanized, bone data were collected using dual-energy X
      ray absorptiometry, peripheral quantitative tomography, and micro-CT imaging
      modalities and via three-point bending or compression mechanical testing methods.
      ZDF and ZDSD diabetic rats exhibited lower bone mineral densities, which
      coincided with declines in structural strength and increased fragility at the
      femoral midshaft and the L4 vertebral body in response to monotonic loading.
      Vertebral trabecular morphology was compromised in both diabetic rodent strains,
      and ZDSD diabetic rats exhibited additional phenotypic impairments to bone
      material properties at the spine. Because the metabolic origin of the T2D-like
      state that develops in the ZDSD rat strain is highly relevant to adult-onset
      diabetes, it is a particularly attractive novel model for future preclinical
      research.

PMID- 19158320
TI  - High doses of dexamethasone induce increased beta-cell proliferation in
      pancreatic rat islets.
AB  - Activation of insulin signaling and cell cycle intermediates is required for
      adult beta-cell proliferation. Here, we report a model to study beta-cell
      proliferation in living rats by administering three different doses of
      dexamethasone (0.1, 0.5, and 1.0 mg/kg ip, DEX 0.1, DEX 0.5, and DEX 1.0,
      respectively) for 5 days. Insulin sensitivity, insulin secretion, and
      histomorphometric data were investigated. Western blotting was used to analyze
      the levels of proteins related to the control of beta-cell growth. DEX 1.0 rats,
      which present moderate hyperglycemia and marked hyperinsulinemia, exhibited a 5.1
      fold increase in beta-cell proliferation and an increase (17%) in beta-cell size,
      with significant increase in beta-cell mass, compared with control rats. The
      hyperinsulinemic but euglycemic DEX 0.5 rats also showed a significant 3.6-fold
      increase in beta-cell proliferation. However, DEX 0.1 rats, which exhibited the
      lowest degree of insulin resistance, compensate for insulin demand by improving
      only islet function. Activation of the insulin receptor substrate
      2/phosphatidylinositol 3-kinase/serine-threonine kinase/ribosomal protein S6
      kinase pathway, as well as protein retinoblastoma in islets from DEX 1.0 and DEX
      0.5, but not in DEX 0.1, rats was also observed. Therefore, increasing doses of
      dexamethasone induce three different degrees of insulin requirement in living
      rats, serving as a model to investigate compensatory beta-cell alterations.
      Augmented beta-cell mass involves beta-cell hyperplasia and, to a lower extent,
      beta-cell hypertrophy. We suggest that alterations in circulating insulin and, to
      a lesser extent, glucose levels could be the major stimuli for beta-cell
      proliferation in the dexamethasone-induced insulin resistance.

PMID- 19158322
TI  - Selective mtDNA mutation accumulation results in beta-cell apoptosis and diabetes
      development.
AB  - To test the hypothesis that somatic mitochondrial (mt)DNA mutation accumulation
      predisposes mice to beta-cell loss and diabetes development, transgenic mice
      expressing a proofreading-deficient mtDNA polymerase-gamma under the control of
      the rat insulin-1 promoter were generated. At 6 wk of age, mtDNA mutations
      reached 0.01% (1.05 mutations/10,000 bp) in islets isolated from transgenic mice.
      This mutational burden is associated with impaired glucose tolerance and a
      diabetes prevalence of 52% in male transgenic mice. Female transgenic mice
      maintain slightly elevated fasting glucose levels, mild glucose intolerance, and
      a diabetes prevalence of 14%. Diabetes in transgenic animals is associated with
      insulin insufficiency that results from a significant reduction in beta-cell
      mass. Importantly, apoptosis of beta-cells is increased 7-fold in female and 11
      fold in male transgenic mice compared with littermate controls. These results are
      consistent with a causative role of somatic mtDNA mutation accumulation in the
      loss of beta-cell mass and diabetes development.

PMID- 19158323
TI  - Estrogens exert a rapid apoptotic action in anterior pituitary cells.
AB  - It is now accepted that estrogens not only stimulate lactotrope proliferation but
      also sensitize anterior pituitary cells to proapoptotic stimuli. In addition to
      their classical mechanism of action through binding to intracellular estrogen
      receptors (ERs), there is increasing evidence that estrogens exert rapid actions
      mediated by cell membrane-localized ERs (mERs). In the present study, we examined
      the involvement of membrane-initiated steroid signaling in the proapoptotic
      action of estradiol in primary cultures of anterior pituitary cells from
      ovariectomized rats by using estren, a synthetic estrogen with no effect on
      classical transcription and a cell-impermeable 17beta-estradiol conjugate (E2
      BSA). Both compounds induced cell death of anterior pituitary cells after 60 min
      of incubation as assessed by flow cytometry and the [3-(4,5-dimethylthiazol-2
      yl)]-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Estren,
      E2, and E2-BSA induced apoptosis of lactotropes and somatotropes as evaluated by
      the deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay and
      immunodetection of prolactin (PRL) and growth hormone (GH). The proapoptotic
      effect of E2-BSA was abrogated by ICI-182,780, an antagonist of ERs. The
      expression of membrane-associated ERalpha was observed in PRL- and GH-bearing
      cells. Our results indicate that estradiol is able to exert a rapid apoptotic
      action in anterior pituitary cells, especially lactotropes and somatotropes, by a
      mechanism triggered by mERs. This mechanism could be involved in anterior
      pituitary cell turnover.

PMID- 19158321
TI  - Intestinal lipid absorption.
AB  - Our knowledge of the uptake and transport of dietary fat and fat-soluble vitamins
      has advanced considerably. Researchers have identified several new mechanisms by
      which lipids are taken up by enterocytes and packaged as chylomicrons for export
      into the lymphatic system or clarified the actions of mechanisms previously known
      to participate in these processes. Fatty acids are taken up by enterocytes
      involving protein-mediated as well as protein-independent processes. Net
      cholesterol uptake depends on the competing activities of NPC1L1, ABCG5, and
      ABCG8 present in the apical membrane. We have considerably more detailed
      information about the uptake of products of lipid hydrolysis, the active
      transport systems by which they reach the endoplasmic reticulum, the mechanisms
      by which they are resynthesized into neutral lipids and utilized within the
      endoplasmic reticulum to form lipoproteins, and the mechanisms by which
      lipoproteins are secreted from the basolateral side of the enterocyte. apoB and
      MTP are known to be central to the efficient assembly and secretion of
      lipoproteins. In recent studies, investigators found that cholesterol,
      phospholipids, and vitamin E can also be secreted from enterocytes as components
      of high-density apoB-free/apoAI-containing lipoproteins. Several of these
      advances will probably be investigated further for their potential as targets for
      the development of drugs that can suppress cholesterol absorption, thereby
      reducing the risk of hypercholesterolemia and cardiovascular disease.

PMID- 19158325
TI  - Protein kinase B activity is required for the effects of insulin on lipid
      metabolism in adipocytes.
AB  - Protein kinase B (PKB) is known to mediate a number of biological responses to
      insulin and growth factors, its role in glucose uptake being one of the most
      extensively studied. In this work, we have employed a recently described
      allosteric inhibitor of PKB, Akti, to clarify the role of PKB in lipid metabolism
      in adipocytes-a subject that has received less attention. Pretreatment of primary
      rat and 3T3L1 adipocytes with Akti resulted in dose-dependent inhibition of PKB
      phosphorylation and activation in response to insulin, without affecting upstream
      insulin signaling [insulin receptor (IR), insulin receptor substrate (IRS)] or
      the insulin-induced phosphoinositide 3-kinase (PI3K)-dependent activation of the
      ERK/p90 ribosomal kinase (RSK) pathway. PKB activity was required for the insulin
      induced activation of phosphodiesterase 3B (PDE3B) and for the antilipolytic
      action of insulin. Moreover, inhibition of PKB activity resulted in a reduction
      in de novo lipid synthesis and in the ability of insulin to stimulate this
      process. The regulation of the rate-limiting lipogenic enzyme acetyl-CoA
      carboxylase (ACC) by insulin through dephosphorylation of S79, which is a target
      for AMP-activated protein kinase (AMPK), was dependent on the presence of active
      PKB. Finally, AMPK was shown to be phosphorylated by PKB on S485 in response to
      insulin, and this was associated with a reduction in AMPK activity. In summary,
      we propose that PKB is required for the positive effects of insulin on lipid
      storage and that regulation of PDE3B and AMPK by PKB is important for these
      effects.

PMID- 19158324
TI  - Regulation of homocysteine homeostasis through the transcriptional coactivator
      PGC-1alpha.
AB  - Plasma homocysteine (Hcy) is an independent risk factor for cardiovascular
      disease. Hcy is a nonprotein amino acid derivative that is generated from the
      methionine cycle, which provides the methyl group for essentially all biological
      methylation reactions. Although plasma Hcy levels are elevated in patients with
      cardiovascular disease, the mechanisms that regulate Hcy homeostasis remain
      poorly defined. In this study, we found that the expression of key enzymes
      involved in Hcy metabolism is induced in the liver in response to fasting. This
      induction coincides with increased expression of peroxisome proliferator
      activated receptor-gamma coactivator (PGC)-1alpha, a transcriptional coactivator
      that regulates hepatic gluconeogenesis and mitochondrial function. PGC-1alpha
      stimulates the expression of genes involved in Hcy metabolism in cultured primary
      hepatocytes as well as in the liver. Adenoviral-mediated expression of PGC-1alpha
      in vivo leads to elevated plasma Hcy levels. In contrast, mice deficient in PGC
      1alpha have lower plasma Hcy concentrations. These results define a novel role
      for the PGC-1alpha coactivator pathway in the regulation of Hcy homeostasis and
      suggest a potential pathogenic mechanism that contributes to
      hyperhomocysteinemia.

PMID- 19158326
TI  - Changing mortality in acute respiratory distress syndrome? Yes, we can!

PMID- 19158327
TI  - Integration of clinical, radiological, and histopathological data in the
      diagnosis of diffuse parenchymal lung diseases.

PMID- 19158328
TI  - Sleep study predictors of prevalent cardiovascular disease.

PMID- 19158329
TI  - Understanding nonspecific interstitial pneumonia: the need for a diagnostic gold
      standard.

PMID- 19158330
TI  - Panic disorder is closely associated with respiratory obstructive illnesses.

PMID- 19158331
TI  - Death after lung transplantation in cystic fibrosis patients infected with
      Burkholderia cepacia.

PMID- 19158332
TI  - Management of convulsive status epilepticus in children.

PMID- 19158333
TI  - A patient with leukaemia turns blue.

PMID- 19158334
TI  - How to use: a pH study.

PMID- 19158335
TI  - Teaching and learning about advocacy.
AB  - Advocacy is an essential skill in the practice of paediatrics, where much of the
      work covers aspects of health as well as disease and where cross-agency work is
      common. Educationally, advocacy is best taught using a competency based approach
      and the key knowledge, skills and attitudes are defined. Central to the knowledge
      field is the evidence base for advocacy, and the UN Convention on the Rights of
      the Child. It is desirable for advocacy skills to be learned through experiential
      learning and examples are offered including letter writing campaigns, an advocacy
      journal club and keeping a diary of cases seen in the clinic. Means are suggested
      for including advocacy training in the core teaching of paediatricians, through a
      combination of theoretical teaching and practical experience. It will be
      necessary also to include advocacy topics in examinations, if there is to be
      genuine prioritisation of this area of practice.

PMID- 19158336
TI  - Neonatal endotracheal intubation: the 7-8-9 rule.

PMID- 19158338
TI  - ATR signaling at a glance.

PMID- 19158339
TI  - A common cofilin activity cycle in invasive tumor cells and inflammatory cells.
AB  - In many cell types, the formation of membrane protrusions and directional
      migration depend on the spatial and temporal regulation of the actin-binding
      protein cofilin. Cofilin, which is important for the regulation of actin
      polymerization initiation, increases the number of actin free barbed ends through
      three mechanisms: its intrinsic actin-nucleation activity; binding and severing
      of existing actin filaments; and recycling actin monomers from old filaments to
      new ones through its actin-depolymerization activity. The increase in free barbed
      ends that is caused by cofilin initiates new actin polymerization, which can be
      amplified by the actin-nucleating ARP2/3 complex. Interestingly, different cell
      systems seem to have different mechanisms of activating cofilin. The initial
      activation of cofilin in mammary breast tumors is dependent on PLCgamma, whereas
      cofilin activation in neutrophils is additionally dependent on dephosphorylation,
      which is promoted through Rac2 signaling. Although the literature seems to be
      confusing and inconsistent, we propose that all of the data can be explained by a
      single activity-cycle model. In this Opinion, we give an overview of cofilin
      activation in both tumor cells and inflammatory cells, and demonstrate how the
      differences in cofilin activation that are observed in various cell types can be
      explained by different starting points in this single common activity cycle.

PMID- 19158340
TI  - The SAM domain of the RhoGAP DLC1 binds EF1A1 to regulate cell migration.
AB  - Deleted in liver cancer 1 (DLC1) is a multi-modular Rho-GTPase-activating protein
      (RhoGAP) and a tumor suppressor. Besides its RhoGAP domain, functions of other
      domains in DLC1 remain largely unknown. By protein precipitation and mass
      spectrometry, we identified eukaryotic elongation factor 1A1 (EF1A1) as a novel
      partner for the sterile alpha motif (SAM) domain of DLC1 but not the SAM domain
      of DLC2. The solution structure of DLC1 SAM revealed a new monomeric fold with
      four parallel helices, similar to that of DLC2 SAM but distinct from other SAM
      domains. Mutating F38, L39 and F40 within a hydrophobic patch retained its
      overall structure but abolished its interaction with EF1A1 with F38 and L39
      forming an indispensable interacting motif. DLC1 SAM did not localize to and was
      not required for DLC1 to suppress the turnover of focal adhesions. Instead, DLC1
      SAM facilitated EF1A1 distribution to the membrane periphery and ruffles upon
      growth factor stimulation. Compared with wild-type DLC1, the non-interactive DLC1
      mutant is less potent in suppressing cell migration, whereas overexpression of
      the DLC1 SAM domain alone, but not the non-interactive mutant SAM or DLC2 SAM,
      greatly enhanced cell migration. This finding reveals a novel contribution of the
      SAM-EF1A1 interaction as a potentially important GAP-independent modulation of
      cell migration by DLC1.

PMID- 19158341
TI  - Positive- and negative-feedback regulations coordinate the dynamic behavior of
      the Ras-Raf-MEK-ERK signal transduction pathway.
AB  - The Ras-Raf-MEK-ERK pathway (or ERK pathway) is an important signal transduction
      system involved in the control of cell proliferation, survival and
      differentiation. However, the dynamic regulation of the pathway by positive- and
      negative-feedback mechanisms, in particular the functional role of Raf kinase
      inhibitor protein (RKIP) are still incompletely understood. RKIP is a
      physiological endogenous inhibitor of MEK phosphorylation by Raf kinases, but
      also participates in a positive-feedback loop in which ERK can inactivate RKIP.
      The aim of this study was to elucidate the hidden dynamics of these feedback
      mechanisms and to identify the functional role of RKIP through combined efforts
      of biochemical experiments and in silico simulations based on an experimentally
      validated mathematical model. We show that the negative-feedback loop from ERK to
      SOS plays a crucial role in generating an oscillatory behavior of ERK activity.
      The positive-feedback loop in which ERK functionally inactivates RKIP also
      enhances the oscillatory activation pattern of ERK. However, RKIP itself has an
      important role in inducing a switch-like behavior of MEK activity. When
      overexpressed, RKIP also causes delayed and reduced responses of ERK. Thus,
      positive- and negative-feedback loops and RKIP work together to shape the
      response pattern and dynamical characteristics of the ERK pathway.

PMID- 19158342
TI  - Functional TRP and ASIC-like channels in cultured urothelial cells from the rat.
AB  - Transient receptor potential (TRP) and acid-sensing ion channels (ASIC) are
      molecular detectors of chemical, mechanical, thermal, and nociceptive stimuli in
      sensory neurons. They have been identified in the urothelium, a tissue considered
      part of bladder sensory pathways, where they might play a role in bladder
      function. This study investigated functional properties of TRP and ASIC channels
      in cultured urothelial cells from the rat using patch-clamp and fura 2 Ca(2+)
      imaging techniques. The TRPV4 agonist 4alpha-phorbol-12,13 didecanoate (4alpha
      PDD; 1-5 microM) and the TRPA1/TRPM8 agonist icilin (50-100 microM) elicited
      transient currents in a high percentage of cells (>70%). 4alpha-PDD responses
      were suppressed by the TRPV4 antagonist HC-010961 (10 microM). The TRPV1 agonist
      capsaicin (1-100 microM) and the TRPA1/TRPM8 agonist menthol (5-200 microM)
      elicited transient currents in a moderate percentage of cells ( approximately
      25%). All of these agonists increased intracellular calcium concentration
      ([Ca(2+)](i)). Most cells responded to more than one TRP agonist (e.g., capsaicin
      and 4alpha-PDD), indicating coexpression of different TRP channels. In the
      presence of the TRPV1 antagonist capsazepine (10 microM), changes in pH induced
      by HCl elicited ionic currents (pH 5.5) and increased [Ca(2+)](i) (pH 6.5) in
      approximately 50% of cells. Changes in pH using acetic acid (pH 5.5) elicited
      biphasic-like currents. Responses induced by acid were sensitive to amiloride (10
      microM). In summary, urothelial cells express multiple TRP and ASIC channels,
      whose activation elicits ionic currents and Ca(2+) influx. These "neuron-like"
      properties might be involved in transmitter release, such as ATP, that can act on
      afferent nerves or smooth muscle to modulate their responses to different
      stimuli.

PMID- 19158343
TI  - Angiotensin-converting enzyme inhibitor-enhanced MR renography: repeated measures
      of GFR and RPF in hypertensive patients.
AB  - This study aims to assess the feasibility of a protocol to diagnose renovascular
      disease using dual MR renography acquisitions: before and after administration of
      angiotensin-converting enzyme inhibitor (ACEi). Results of our simulation study
      aimed at testing the reproducibility of glomerular filtration rate (GFR) and
      renal plasma flow demonstrate that for a fixed overall dose of 12 ml gadolinium
      based contrast material (500 mmol/l), the second dose should be approximately
      twice as large as the first dose. A three-compartment model for analyzing the
      second-injection data was shown to appropriately handle the tracer residue from
      the first injection. The optimized protocol was applied to 18 hypertensive
      patients without renovascular disease, showing minimal systematic difference in
      GFR measurements before and after ACEi of 0.8 +/- 4.4 ml/min or 2.7 +/- 14.9%.
      For 10 kidneys with significant renal artery stenosis, GFR decreased
      significantly after ACEi (P < 0.001, T value = 3.79), and the difference in GFR
      measurements before and after ACEi averaged 8.3 +/- 6.9 ml/min or 26.2 +/- 43.9%.
      Dual-injection MRI with optimized dose distribution appears promising for ACEi
      renography by offering measures of GFR changes with clinically acceptable
      precision and accuracy.

PMID- 19158344
TI  - Oncostatin M pathway plays a major role in the renal acute phase response.
AB  - The acute phase response is traditionally characterized by hepatic synthesis of
      proteins as an inflammatory response to injury, with interleukin-6 (IL-6) being
      the key mediator. In contrast, microarray studies in human renal transplant
      implantation biopsies indicate a strong acute phase response in the deceased
      donor kidney, associated with a significant upregulation of oncostatin M receptor
      beta (OSMR). The aim of this study was to determine whether the kidney can
      generate a strong acute phase response, mediated by the OSM/OSMR gateway. Genes
      associated with the IL-6 cytokine family and acute phase reactants were analyzed
      by real-time RT-PCR in four groups of human biopsies spanning a spectrum of renal
      injury. OSM, OSMR, and fibrinogen beta (FGB) were progressively more highly
      expressed from prenephrectomy, living donor, deceased donor, to discarded donor
      kidneys, suggesting correlation with severity of injury and local renal
      synthesis. Acute phase response gene expression was analyzed in human proximal
      tubular cells in culture in response to OSM. OSM induced a significant increase
      in expression of FGB, OSMR, serpin peptidase inhibitor A1, IL-6, and
      lipopolysaccharide binding protein, and a decrease in IL-6R. These changes were
      largely attenuated by coincubation with an OSMR blocking antibody, indicating the
      OSM effect was mediated through OSMR. OSM also resulted in a significantly
      altered expression of acute phase genes compared with IL-6 or leukemia inhibitory
      factor, suggesting that OSM is the predominant cytokine mediating the renal
      tubular acute phase response. In conclusion, the renal parenchyma is capable of
      generating a strong acute phase response, likely mediated via OSM/OSMR.

PMID- 19158345
TI  - TRPMLs: in sickness and in health.
AB  - TRPML1, TRPML2 and TRPML3 belong to the mucolipin family of the TRP superfamily
      of ion channels. The founding member of this family, TRPML1, was cloned during
      the search for the genetic determinants of the lysosomal storage disease
      mucolipidosis type IV (MLIV). Mucolipins are predominantly expressed within the
      endocytic pathway, where they appear to regulate membrane traffic and/or
      degradation. The physiology of mucolipins raises some of the most interesting
      questions of modern cell biology. Their traffic and localization is a multistep
      process involving a system of adaptor proteins, while their ion channel activity
      possibly exemplifies the rare cases of regulation of endocytic traffic and
      hydrolysis by ion channels. Finally, dysregulation of mucolipins results in cell
      death leading to neurodegenerative phenotypes of MLIV and of the varitint-waddler
      mouse model of familial deafness. The present review discusses current knowledge
      and questions regarding this novel family of disease-relevant ion channels with a
      specific focus on mucolipin regulation and their role in membrane traffic and
      cell death. Since mucolipins are ubiquitously expressed, this review may be
      useful for a wide audience of basic biologists and clinicians.

PMID- 19158346
TI  - PERP, a p53 proapoptotic target, mediates apoptotic cell death in renal ischemia.
AB  - The p53 tumor suppressor gene plays a crucial role in mediating apoptotic cell
      death in renal ischemia-reperfusion injury (IRI). To further elucidate the p53
      dependent pathway, we investigated the role of the p53 apoptosis effector related
      to PMP-22 (PERP), an apoptosis-associated p53 transcriptional target. PERP mRNA
      and protein are highly induced in the outer medullary proximal tubular cells
      (PTC) of ischemic kidneys postreperfusion at 3, 12, and 24 h in a p53-dependent
      manner. In PTC, overexpression of PERP augmented the rate of apoptosis following
      hypoxia by inducing mitochondrial permeability and subsequent release of
      cytochrome c, apoptosis-inducing factor (AIF), and caspase 9 activation. In
      addition, silencing of the PERP gene with short hairpin RNA prevented apoptosis
      in hypoxia-mediated injury by precluding mitochondrial dysfunction and consequent
      cytochrome c and AIF translocation. These data suggest that PERP is a key
      effector of p53-mediated apoptotic pathways and is a potential therapeutic target
      for renal IRI.

PMID- 19158348
TI  - Trif is not required for immune complex glomerulonephritis: dying cells activate
      mesangial cells via Tlr2/Myd88 rather than Tlr3/Trif.
AB  - Viral RNA or bacterial products can activate glomerular mesangial cells via a
      subset of Toll-like receptors (Tlr). Because Tlr2-deficient mice were recently
      found to have attenuated nephrotoxic serum nephritis (NSN), we hypothesized that
      endogenous Tlr agonists can activate glomerular mesangial cells. Primary
      mesangial cells from C57BL/6 mice expressed Tlr1-6 and Tlr11 mRNA at considerable
      levels and produced Il-6 when being exposed to the respective Tlr ligands.
      Exposure to necrotic cells activated cultured primary mesangial cells to produce
      Il-6 in a Tlr2/Myd88-dependent manner. Apoptotic cells activated cultured
      mesangial cells only when being enriched to high numbers. Apoptotic cell-induced
      Il-6 release was Myd88 dependent, and only purified apoptotic cell RNA induced
      Trif signaling in mesangial cells. Does Trif signaling contribute to disease
      activity in glomerulonephritis? To answer this question, we induced autologous
      NSN by injection of NS raised in rabbits in Trif-mutant and wild-type mice. Lack
      of Trif did not alter the functional and histomorphological abnormalities of NSN,
      including the evolution of anti-rabbit IgG and anti-rabbit-specific nephritogenic
      T cells. We therefore conclude that apoptotic cell RNA is a poor activator of
      Trif signaling in mesangial cells and that necrotic cells' releases rather
      activate mesangial cells via the Tlr2/Myd88 signaling pathway.

PMID- 19158347
TI  - SGK1-sensitive renal tubular glucose reabsorption in diabetes.
AB  - The hyperglycemia of diabetes mellitus increases the filtered glucose load beyond
      the maximal tubular transport rate and thus leads to glucosuria. Sustained
      hyperglycemia, however, may gradually increase the maximal renal tubular
      transport rate and thereby blunt the increase of urinary glucose excretion. The
      mechanisms accounting for the increase of renal tubular glucose transport have
      remained ill-defined. A candidate is the serum- and glucocorticoid-inducible
      kinase SGK1. The kinase has been shown to stimulate Na(+)-coupled glucose
      transport in vitro and mediate the stimulation of electrogenic intestinal glucose
      transport by glucocorticoids in vivo. SGK1 expression is confined to glomerula
      and distal nephron in intact kidneys but may extend to the proximal tubule in
      diabetic nephropathy. To explore whether SGK1 modifies glucose transport in
      diabetic kidneys, Akita mice (akita(+/-)), which develop spontaneous diabetes,
      have been crossbred with gene-targeted mice lacking SGK1 on one allele (sgk1(+/
      )) to eventually generate either akita(+/-)/sgk1(-/-) or akita(+/-)/sgk1(+/+)
      mice. Both akita(+/-)/sgk1(-/-) and akita(+/-)/sgk1(+/+) mice developed profound
      hyperglycemia (>20 mM) within approximately 6 wk. Body weight and plasma glucose
      concentrations were not significantly different between these two genotypes.
      However, urinary excretion of glucose and urinary excretion of fluid, Na(+), and
      K(+), as well as plasma aldosterone concentrations, were significantly higher in
      akita(+/-)/sgk1(-/-) than in akita(+/-)/sgk1(+/+) mice. Studies in isolated
      perfused proximal tubules revealed that the electrogenic glucose transport was
      significantly lower in akita(+/-)/sgk1(-/-) than in akita(+/-)/sgk1(+/+) mice.
      The data provide the first evidence that SGK1 participates in the stimulation of
      renal tubular glucose transport in diabetic kidneys.

PMID- 19158349
TI  - In vitro selection and characterization of DNA aptamers specific for
      phospholamban.
AB  - Calcium transport across the membrane of the sarcoplasmic reticulum (SR) plays an
      important role in the regulation of heart muscle contraction and relaxation. The
      sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) 2a is responsible for Ca(2+)
      up-take by this organelle and is inhibited in a reversible manner by
      phospholamban, another SR membrane protein. Thus, alleviation of phospholamban
      mediated inhibition of SERCA2a is a potential therapeutic option for heart
      failure and cardiomyopathy. We have now applied the systematic evolution of
      ligands by exponential enrichment protocol to a library of single-stranded DNA
      molecules containing a randomized 40-nucleotide sequence to isolate aptamers that
      bind phospholamban. One of the obtained aptamers, designated Apt-9, was found to
      specifically bind to the cytoplasmic region of phospholamban in vitro with high
      affinity (dissociation constant, approximately 20 nM). Apt-9 increased the Ca(2+)
      dependent ATPase activity of cardiac SR vesicles but not that of SR vesicles from
      skeletal muscle in a concentration-dependent manner. It also shifted the Ca(2+)
      concentration-response curve for this ATPase activity to the left. These effects
      of Apt-9 were not mimicked by an oligonucleotide with a scrambled version of the
      Apt-9 sequence. Thus, our results indicate that Apt-9 activates SERCA2a by
      alleviating the inhibitory effect of phospholamban on this ATPase, and they
      suggest that phospholamban-specific aptamers warrant further investigation as
      potential therapeutic agents for heart failure and cardiomyopathy.

PMID- 19158350
TI  - IL-6 and serum amyloid A synergy mediates angiotensin II-induced muscle wasting.
AB  - Animal studies suggest that increased levels of circulating angiotensin II
      (AngII) could contribute to the loss of lean body mass in chronic kidney disease,
      but the mechanism by which this occurs is unclear. Here, AngII infusion increased
      circulating IL-6 and its hepatic production in wild-type mice, suggesting that
      AngII-induced inflammation may trigger muscle loss. AngII infusion also
      stimulated the suppressor of cytokine signaling (SOCS3) in muscle, which led to
      loss of insulin receptor substrate 1 (IRS-1), thereby impairing insulin/IGF-1
      signaling and enhancing protein degradation. All of these responses to AngII were
      suppressed in IL-6-deficient mice. Recombinant human IL-6 (rhIL-6) treatment of
      cultured myotubes only minimally increased SOCS3, however, suggesting the
      contribution of other mediators. Because AngII increases hepatic serum amyloid A
      (SAA) expression in an IL-6-dependent manner, we treated wild-type mice with rhIL
      6 and an SAA1-overexpressing adenovirus; the combination led to a significantly
      greater increase in SOCS3 and decrease in IRS-1 compared with either rhIL-6 or
      SAA1 alone. We observed similar effects on SOCS3 and IRS-1 when we treated
      cultured muscle myotubes with rhIL-6 and SAA1. Taken together, these results
      suggest an interorgan response to high levels of AngII: Hepatic production of IL
      6 and SAA increases, and these mediators act synergistically to impair
      insulin/IGF-1 signaling, which promotes muscle proteolysis. Targeting the high
      levels of IL-6 and SAA in catabolic disorders might be a therapeutic approach to
      prevent muscle wasting.

PMID- 19158351
TI  - Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators
      in proximal tubular cells.
AB  - Increased consumption of fructose may play an important role in the epidemic of
      metabolic syndrome and may presage the development of diabetes, cardiovascular
      disease, and chronic kidney disease. Once in the cell, fructose is phosphorylated
      by ketohexokinase (KHK), leading to consumption of ATP, formation of AMP, and
      generation of uric acid through xanthine oxidoreductase (XOR). This study aimed
      to examine the direct effects of fructose in human kidney proximal tubular cells
      (HK-2) and whether they are mediated by the fructose metabolism via KHK. At a
      similar concentration to that observed in peripheral blood after a meal, fructose
      induced production of monocyte chemotactic protein 1 (MCP-1) and reactive oxygen
      species in HK-2 cells. Knockdown of KHK by stable transfection with small hairpin
      RNA demonstrated that these processes were KHK dependent. Several antioxidants,
      including specific inhibitors of NADPH oxidase and XOR, prevented MCP-1
      secretion. We detected XOR mRNA in HK-2 cells and confirmed its activity by
      identifying uric acid by mass spectrometry. Fructose increased intracellular uric
      acid, and uric acid induced production of MCP-1 as well. In summary, postprandial
      concentrations of fructose stimulate redox- and urate-dependent inflammatory
      mediators in proximal tubular cells.

PMID- 19158352
TI  - Characterization of PKD protein-positive exosome-like vesicles.
AB  - Proteins associated with autosomal dominant and autosomal recessive polycystic
      kidney disease (polycystin-1, polycystin-2, and fibrocystin) localize to various
      subcellular compartments, but their functional site is thought to be on primary
      cilia. PC1+ vesicles surround cilia in Pkhd1(del2/del2) mice, which led us to
      analyze these structures in detail. We subfractionated urinary exosome-like
      vesicles (ELVs) and isolated a subpopulation abundant in polycystin-1,
      fibrocystin (in their cleaved forms), and polycystin-2. This removed Tamm
      Horsfall protein, the major contaminant, and subfractionated ELVs into at least
      three different populations, demarcated by the presence of aquaporin-2,
      polycystin-1, and podocin. Proteomic analysis of PKD ELVs identified 552 proteins
      (232 not yet in urinary proteomic databases), many of which have been implicated
      in signaling, including the molecule Smoothened. We also detected two other
      protein products of genes involved in cystic disease: Cystin, the product of the
      mouse cpk locus, and ADP-ribosylation factor-like 6, the product of the human
      Bardet-Biedl syndrome gene (BBS3). Our proteomic analysis confirmed that cleavage
      of polycystin-1 and fibrocystin occurs in vivo, in manners consistent with
      cleavage at the GPS site in polycystin-1 and the proprotein convertase site in
      fibrocystin. In vitro, these PKD ELVs preferentially interacted with primary
      cilia of kidney and biliary epithelial cells in a rapid and highly specific
      manner. These data suggest that PKD proteins are shed in membrane particles in
      the urine, and these particles interact with primary cilia.

PMID- 19158353
TI  - RAGE-induced cytosolic ROS promote mitochondrial superoxide generation in
      diabetes.
AB  - Damaged mitochondria generate an excess of superoxide, which may mediate tissue
      injury in diabetes. We hypothesized that in diabetic nephropathy, advanced
      glycation end-products (AGEs) lead to increases in cytosolic reactive oxygen
      species (ROS), which facilitate the production of mitochondrial superoxide. In
      normoglycemic conditions, exposure of primary renal cells to AGEs, transient
      overexpression of the receptor for AGEs (RAGE) with an adenoviral vector, and
      infusion of AGEs to healthy rodents each induced renal cytosolic oxidative
      stress, which led to mitochondrial permeability transition and deficiency of
      mitochondrial complex I. Because of a lack of glucose-derived NADH, which is the
      substrate for complex I, these changes did not lead to excess production of
      mitochondrial superoxide; however, when we performed these experiments in
      hyperglycemic conditions in vitro or in diabetic rats, we observed significant
      generation of mitochondrial superoxide at the level of complex I, fueled by a
      sustained supply of NADH. Pharmacologic inhibition of AGE-RAGE-induced
      mitochondrial permeability transition in vitro abrogated production of
      mitochondrial superoxide; we observed a similar effect in vivo after inhibiting
      cytosolic ROS production with apocynin or lowering AGEs with alagebrium.
      Furthermore, RAGE deficiency prevented diabetes-induced increases in renal
      mitochondrial superoxide and renal cortical apoptosis in mice. Taken together,
      these studies suggest that AGE-RAGE-induced cytosolic ROS production facilitates
      mitochondrial superoxide production in hyperglycemic environments, providing
      further evidence of a role for the advanced glycation pathway in the development
      and progression of diabetic nephropathy.

PMID- 19158354
TI  - C3a mediates epithelial-to-mesenchymal transition in proteinuric nephropathy.
AB  - Tubulointerstitial inflammation and progressive fibrosis are common pathways that
      lead to kidney failure in proteinuric nephropathies. Activation of the complement
      system has been implicated in the development of tubulointerstitial injury in
      clinical and animal studies, but the mechanism by which complement induces kidney
      injury is not fully understood. Here, we studied the effect of complement on the
      phenotype of tubular epithelial cells. Tubular epithelial cells exposed to serum
      proteins adopted phenotypic and functional characteristics of mesenchymal cells.
      Expression of E-cadherin protein decreased and expression of both alpha-smooth
      muscle actin protein and collagen I mRNA increased. Exposure of the cells to the
      complement anaphylotoxin C3a induced similar features. Treating with a C3a
      receptor (C3aR) antagonist prevented both C3a- and serum-induced epithelial-to
      mesenchymal transition. In the adriamycin-induced proteinuria model, C3aR
      deficient mice demonstrated less injury, preserved renal function, and improved
      survival compared with wild-type mice. Furthermore, the kidneys of C3aR-deficient
      mice had significantly less interstitial collagen I and alpha-smooth muscle
      actin. In summary, the complement anaphylotoxin C3a is an important mediator of
      glomerular and tubulointerstitial injury and can induce tubular epithelial-to
      mesenchymal transition.

PMID- 19158355
TI  - Thiazolidinedione-induced fluid retention is independent of collecting duct
      alphaENaC activity.
AB  - Thiazolidinediones are agonists of peroxisome proliferator-activated receptor
      gamma (PPARgamma) that can induce fluid retention and weight gain through unclear
      mechanisms. To test a proposed role for the epithelial sodium channel ENaC in
      thiazolidinedione-induced fluid retention, we used mice with conditionally
      inactivated alphaENaC in the collecting duct (Scnn1a(loxloxCre) mice). In control
      mice, rosiglitazone did not alter plasma aldosterone levels or protein expression
      of ENaC subunits in the kidney, but did increase body weight, plasma volume, and
      the fluid content of abdominal fat pads, and decreased hematocrit.
      Scnn1a(loxloxCre) mice provided functional evidence for blunted Na+ uptake in the
      collecting duct, but still exhibited rosiglitazone-induced fluid retention.
      Moreover, treatment with rosiglitazone or pioglitazone did not significantly
      alter the open probability or number of ENaC channels per patch in isolated,
      split-open cortical collecting ducts of wild-type mice. Finally, patch-clamp
      studies in primary mouse inner medullary collecting duct cells did not detect
      ENaC activity but did detect a nonselective cation channel upregulated by
      pioglitazone. These data argue against a primary and critical role of ENaC in
      thiazolidinedione-induced fluid retention.

PMID- 19158356
TI  - New equations to estimate GFR in children with CKD.
AB  - The Schwartz formula was devised in the mid-1970s to estimate GFR in children.
      Recent data suggest that this formula currently overestimates GFR as measured by
      plasma disappearance of iohexol, likely a result of a change in methods used to
      measure creatinine. Here, we developed equations to estimate GFR using data from
      the baseline visits of 349 children (aged 1 to 16 yr) in the Chronic Kidney
      Disease in Children (CKiD) cohort. Median iohexol-GFR (iGFR) was 41.3 ml/min per
      1.73 m(2) (interquartile range 32.0 to 51.7), and median serum creatinine was 1.3
      mg/dl. We performed linear regression analyses assessing precision, goodness of
      fit, and accuracy to develop improvements in the GFR estimating formula, which
      was based on height, serum creatinine, cystatin C, blood urea nitrogen, and
      gender. The best equation was: GFR(ml/min per 1.73 m(2))=39.1[height (m)/Scr
      (mg/dl)](0.516) x [1.8/cystatin C (mg/L)](0.294)[30/BUN
      (mg/dl)](0.169)[1.099](male)[height (m)/1.4](0.188). This formula yielded 87.7%
      of estimated GFR within 30% of the iGFR, and 45.6% within 10%. In a test set of
      168 CKiD patients at 1 yr of follow-up, this formula compared favorably with
      previously published estimating equations for children. Furthermore, with height
      measured in cm, a bedside calculation of 0.413*(height/serum creatinine),
      provides a good approximation to the estimated GFR formula. Additional studies of
      children with higher GFR are needed to validate these formulas for use in
      screening all children for CKD.

PMID- 19158357
TI  - Cyclooxygenase-2 mediates dialysate-induced alterations of the peritoneal
      membrane.
AB  - During peritoneal dialysis (PD), exposure of the peritoneal membrane to
      nonphysiologic solutions causes inflammation, ultimately leading to altered
      structure and function. Myofibroblasts, one of the cell types that contribute to
      dysfunction of the peritoneal membrane, can originate from mesothelial cells
      (MCs) by epithelial-to-mesenchymal transition (EMT), a process that has been
      associated with an increased rate of peritoneal transport. Because cyclooxygenase
      2 (COX-2) is induced by inflammation, we studied the role of COX-2 in the
      deterioration of the peritoneal membrane. We observed that nonepithelioid MCs
      found in peritoneal effluent expressed higher levels of COX-2 than epithelioid
      MCs. The mass transfer coefficient for creatinine correlated with MC phenotype
      and with COX-2 levels. Although COX-2 was upregulated during EMT of MCs in vitro,
      COX-2 inhibition did not prevent EMT. In a mouse model of PD, however, COX-2
      inhibition with Celecoxib resulted in reduced fibrosis and in partial recovery of
      ultrafiltration, outcomes that were associated with a reduction of inflammatory
      cells. Furthermore, PD fluid with a low content of glucose degradation products
      did not induce EMT or COX-2; the peritoneal membranes of mice treated with this
      fluid showed less worsening than mice exposed to standard fluid. In conclusion,
      upregulation of COX-2 during EMT may mediate peritoneal inflammation, suggesting
      COX-2 inhibition as a potential strategy to ameliorate peritoneal deterioration
      in PD patients.

PMID- 19158358
TI  - Presence of urinary Haufen accurately predicts polyomavirus nephropathy.
AB  - There are no accurate, noninvasive tests to diagnose BK polyomavirus nephropathy,
      a common infectious complication after renal transplantation. This study
      evaluated whether the qualitative detection of cast-like, three-dimensional
      polyomavirus aggregates ("Haufen") in the urine accurately predicts BK
      polyomavirus nephropathy. Using negative-staining electron microscopy, we sought
      Haufen in 194 urine samples from 139 control patients and in 143 samples from 21
      patients with BK polyomavirus nephropathy. Haufen detection was correlated with
      pathology in concomitant renal biopsies and BK viruria (decoy cell shedding and
      viral load assessments by PCR) and BK viremia (viral load assessments by PCR).
      Haufen originated from renal tubules containing virally lysed cells, and the
      detection of Haufen in the urine correlated tightly with biopsy confirmed BK
      polyomavirus nephropathy (concordance rate 99%). A total of 77 of 143 urine
      samples from 21 of 21 patients with BK polyomavirus nephropathy (disease stages A
      C) contained Haufen, and during follow-up (3 to 120 wk), their presence or
      absence closely mirrored the course of renal disease. All controls were Haufen
      negative, however, high viremia or viruria were detected in 8% and 41% of control
      samples, respectively. kappa statistics showed fair to good agreement of viruria
      and viremia with BK polyomavirus nephropathy or with Haufen shedding and
      demonstrated an excellent agreement between Haufen and polyomavirus nephropathy
      (kappa 0.98). Positive and negative predictive values of Haufen for BK
      polyomavirus nephropathy were 97% and 100%, respectively. This study shows that
      shedding of urinary Haufen and not BK viremia and viruria accurately mark BK
      polyomavirus nephropathy. It suggests that the detection of Haufen may serve as a
      noninvasive means to diagnose BK polyomavirus nephropathy in the urine.

PMID- 19158359
TI  - PAQRs: a counteracting force to ceramides?
AB  - In recent years, sphingolipids have garnered increasing attention for their roles
      in modulating intracellular signaling events. Circulating factors associated with
      obesity promote excess accumulation of ceramide or glucosylceramide derivatives,
      which impair insulin action in peripheral tissues. In this issue, Villa et al.
      (p. 866) provide evidence that, in yeast, the progestin and adipoQ receptor
      superfamily of receptors mediate their effects via a novel ceramidase activity,
      generating sphingoid base as a second messenger.

PMID- 19158360
TI  - A small-molecule triptolide suppresses angiogenesis and invasion of human
      anaplastic thyroid carcinoma cells via down-regulation of the nuclear factor
      kappa B pathway.
AB  - Anaplastic thyroid carcinoma (ATC) is among the most aggressive malignancies
      known and is characterized with rapid growth, early invasion, and complete
      refractoriness to current therapies. Here we report that triptolide, a small
      molecule from a Chinese herb, could potently inhibit proliferation in vitro,
      angiogenesis in vivo, and invasion in a Matrigel model in human ATC cell line TA
      K cells at nanomolar concentrations. We further elucidate that triptolide
      inhibits the nuclear factor-kappaB (NF-kappaB) transcriptional activity via
      blocking the association of p65 subunit with CREB-binding protein (CBP)/p300 in
      the early stage and via decreasing the protein level of p65 in the late stage.
      Expression of the NF-kappaB targeting genes cyclin D1, vascular endothelial
      growth factor, and urokinase-type plasminogen activator is significantly reduced
      by triptolide in both TA-K and 8505C human ATC cell lines, which are well known
      to be critical for proliferation, angiogenesis, and invasion in solid tumors. Our
      findings suggest that triptolide may function as a small molecule inhibitor of
      tumor angiogenesis and invasion and may provide novel mechanistic insights into
      the potential therapy for human ATC.

PMID- 19158361
TI  - Interaction of cytochrome P450 3A4 and UDP-glucuronosyltransferase 2B7: evidence
      for protein-protein association and possible involvement of CYP3A4 J-helix in the
      interaction.
AB  - We have reported that the protein-protein interaction between UDP
      glucuronosyltransferase (UGT) 2B7 and cytochrome P450 3A4 (CYP3A4) alters UGT2B7
      function. However, the domain(s) involved in the interaction are largely unknown.
      To address this issue, we examined in more detail the CYP3A4-UGT2B7 association
      by means of immunoprecipitation, overlay assay, and cross-linking involving 1
      ethyl-3-[3-(dimethylamino)propyl]carbodiimide. Purified CYP3A4 or glutathione
      transferase (GST)-tagged CYP3A4 was cross-linked to UGT2B7 in solubilized
      baculosomes. The formation of the cross-linked complex was detected by
      immunoblotting using both antibodies against CYP3A4 and UGTs. Although the GST
      tagged CYP3A4 containing the region ranging from Tyr25 to Ala503 was cross-linked
      to UGT2B7, the same did not occur when another construct containing Met145 to
      His267 was used. This observation was consistent with the result of the overlay
      assay indicating that CYP3A4 lacking the N-terminal hydrophobic segment retains
      the ability to associate with UGT2B7, whereas the Met145-to-His267 region loses
      this capacity. Although the Met145-to-His267 peptide was recognized by one anti
      CYP3A4 antibody that has the ability to coimmunoprecipitate UGT2B7, it was not
      recognized by another antibody incapable of coimmunoprecipitating UGT2B7. The
      epitope of the latter antibody was mapped to the Leu331-to-Lys342 region, which
      is located on the J-helix of CYP3A4. Taken together, the results obtained suggest
      that 1) CYP3A4 and UGT2B7 are a pair of enzymes in proximity to each other and 2)
      either the Leu331-to-Lys342 domain or the surrounding region plays a role in the
      interaction with UGT2B7, whereas the hydrophobic Met145-to-His267 region does not
      contribute to this interaction.

PMID- 19158362
TI  - Cross-talk between integrins and oncogenes modulates chemosensitivity.
AB  - Chemotherapy often relies on cancer cell death resulting from DNA damage. The p53
      tumor suppressor pathway that is an important player in DNA damage response is
      frequently inactivated in cancer. Genotoxicants also activate DNA damage
      independent stress pathways and activity of oncogenic signaling and adhesive
      interactions with the cancer microenvironment can have a strong impact on
      chemosensitivity. Here, we have investigated how two different oncogenes modulate
      the response to genotoxicants in the context of two classes of integrin adhesion
      receptors. Epithelial cells expressing either beta1 or beta3 integrins, in which
      p53 activity is suppressed, undergo G(2) arrest but show little apoptosis after
      treatment with cisplatin or other genotoxicants. The apoptotic response is
      strongly enhanced by the c-Src[Y530F] oncogene in cells expressing beta1
      integrins, whereas such sensitization is reduced when these cells are engineered
      to express beta3 integrins instead. The H-Ras[G12V] oncogene fails to sensitize,
      regardless of the integrin expression profile. The enhanced sensitivity induced
      by c-Src[Y530F] in the context of beta1 integrins does not rely on p53-mediated
      DNA damage signaling but instead involves increased endoplasmic reticulum stress
      and caspase-3 activation. Our data implicate that the expression profiles of
      oncogenes and integrins strongly affect the response to chemotherapeutics and may
      thus determine the efficacy of chemotherapy.

PMID- 19158364
TI  - HapMap methylation-associated SNPs, markers of germline DNA methylation,
      positively correlate with regional levels of human meiotic recombination.
AB  - Inter-individual and regional variability in recombination rates cannot be fully
      explained by the DNA sequence itself. Epigenetic mechanisms might be one
      additional factor affecting recombination. A biochemical approach to studying
      human germline methylation is difficult. We used the density of the 434,198
      nonredundant methylation-associated SNPs (mSNPs) in the derived allele HapMap
      data set as a surrogate marker for germline DNA methylation. We validated our
      methodology by demonstrating that the mSNP density confirmed known patterns of
      genomic methylation, including the hypermutability of methylated cytosine and
      hypomethylation of CpG islands. Using this approach, we found a genome-wide
      positive correlation between germline methylation and regional recombination rate
      (500-kb windows: r = 0.622, P < 10(-15)). This remained significant with multiple
      correlations correcting for sequence features known to affect recombination, such
      as GC content and CpG dinucleotides (500-kb windows: r = 0.172, P < 10(-15)).
      Using the ENCODE data set for increased resolution, we found a positive
      correlation between germline DNA methylation and recombination rate (50-kb
      windows: r = 0.301, P = 0.002). This correlation was further strengthened when
      corrected for sequence features affecting recombination (50-kb windows: r =
      0.445, P < 0.0001). In the Human Epigenome Project data set there was increased
      DNA methylation in regions within recombination hot spots in male germ cells
      (0.632 vs. 0.557, P = 0.007). The relationship we observed between germline DNA
      methylation and recombination could be explained in two ways that are not
      mutually exclusive: DNA methylation could indicate preferred sites for
      recombination, or methylation following recombination could inhibit further
      recombination, perhaps by being part of the enigmatic molecular pathway mediating
      crossover interference.

PMID- 19158363
TI  - High-resolution DNA-binding specificity analysis of yeast transcription factors.
AB  - Transcription factors (TFs) regulate the expression of genes through sequence
      specific interactions with DNA-binding sites. However, despite recent progress in
      identifying in vivo TF binding sites by microarray readout of chromatin
      immunoprecipitation (ChIP-chip), nearly half of all known yeast TFs are of
      unknown DNA-binding specificities, and many additional predicted TFs remain
      uncharacterized. To address these gaps in our knowledge of yeast TFs and their
      cis regulatory sequences, we have determined high-resolution binding profiles for
      89 known and predicted yeast TFs, over more than 2.3 million gapped and ungapped
      8-bp sequences ("k-mers"). We report 50 new or significantly different direct DNA
      binding site motifs for yeast DNA-binding proteins and motifs for eight proteins
      for which only a consensus sequence was previously known; in total, this
      corresponds to over a 50% increase in the number of yeast DNA-binding proteins
      with experimentally determined DNA-binding specificities. Among other novel
      regulators, we discovered proteins that bind the PAC (Polymerase A and C) motif
      (GATGAG) and regulate ribosomal RNA (rRNA) transcription and processing, core
      cellular processes that are constituent to ribosome biogenesis. In contrast to
      earlier data types, these comprehensive k-mer binding data permit us to consider
      the regulatory potential of genomic sequence at the individual word level. These
      k-mer data allowed us to reannotate in vivo TF binding targets as direct or
      indirect and to examine TFs' potential effects on gene expression in
      approximately 1,700 environmental and cellular conditions. These approaches could
      be adapted to identify TFs and cis regulatory elements in higher eukaryotes.

PMID- 19158368
TI  - Ethical and legal obligation to avoid long-term tunneled catheter access.
AB  - Despite recent national initiatives promoting the arteriovenous fistula as the
      initial, primary, and sole vascular access to be used by hemodialysis patients
      and recommending a decrease in the prevalence of tunneled cuffed catheters to
      less than 10%, the prevalence of tunneled cuffed catheters as hemodialysis access
      is increasing. This study describes the risks of tunneled cuffed catheters,
      explores the reasons why they remain prevalent, and presents the stance that
      nephrologists have an obligation to offer tunneled cuffed catheters only for
      temporary use and not as an acceptable alternative for long-term vascular access
      to patients for whom a properly functioning arteriovenous fistula or graft is
      possible. Recommendations for tunneled cuffed catheter use were based on dialysis
      clinical practice guidelines and the medical evidence regarding outcomes of use
      of arteriovenous fistulas and tunneled cuffed catheters. The authors found that
      compared with dialysis with arteriovenous fistulas, long-term dialysis with
      tunneled cuffed catheters is associated with (1) two to threefold increased risk
      of death, (2) a five to 10-fold increased risk of serious infection, (3)
      increased hospitalization, (4) a decreased likelihood of adequate dialysis, and
      (5) an increased number of vascular access procedures. To adequately inform
      patients about access options, nephrologists are ethically obligated to
      systematically explain to patients the harms of tunneled cuffed catheters. If
      catheters must be used to initiate dialysis, nephrologists should present
      catheters only as "temporary" measures and "unsafe for long-term use."

PMID- 19158367
TI  - Membranous glomerulonephritis with ANCA-associated necrotizing and crescentic
      glomerulonephritis.
AB  - BACKGROUND AND OBJECTIVES: Only rare cases of concurrent membranous
      glomerulonephritis (MGN) and antineutrophil cytoplasmic antibody (ANCA)
      associated necrotizing and crescentic glomerulonephritis (NCGN) have been
      reported. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The authors report the
      clinical and pathologic findings in 14 patients with MGN and ANCA-associated
      NCGN. RESULTS: The cohort consisted of eight men and six women with a mean age of
      58.7 yr. ANCA positivity was documented by indirect immunofluorescence or ELISA
      in all patients. Indirect immunofluorescence was positive in 13 patients (seven P
      ANCA, five C-ANCA, one atypical ANCA). ELISA was positive in nine of 10 patients
      (five MPO-ANCA, three PR3-ANCA, one MPO- and PR3-ANCA). Clinical presentation
      included heavy proteinuria (mean 24-hr urine protein 6.5 g/d), hematuria, and
      acute renal failure (mean creatinine 4.4 mg/dl). Pathologic evaluation revealed
      MGN and NCGN, with crescents involving a mean of 32% of glomeruli. On
      ultrastructural evaluation, the majority of cases showed stage I or II membranous
      changes. Follow-up was available for 13 patients, 12 of whom were treated with
      steroids and cyclophosphamide. At a mean follow-up of 24.3 mo, five patients
      progressed to ESRD, seven had stabilization or improvement in renal function, and
      one had worsening renal function. Five patients, including three with ESRD, died
      during the follow-up period. The only independent predictor of progression to
      ESRD was serum creatinine at biopsy. CONCLUSIONS: MGN with ANCA-associated NCGN
      is a rare dual glomerulopathy seen in patients with heavy proteinuria, acute
      renal failure, and active urine sediment. Prognosis is variable, with 50% of
      patients reaching endpoints of ESRD or death.

PMID- 19158369
TI  - Iron-magnesium hydroxycarbonate (fermagate): a novel non-calcium-containing
      phosphate binder for the treatment of hyperphosphatemia in chronic hemodialysis
      patients.
AB  - BACKGROUND AND OBJECTIVES: This phase II study tested the safety and efficacy of
      fermagate, a calcium-free iron and magnesium hydroxycarbonate binder, for
      treating hyperphosphatemia in hemodialysis patients. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: A randomized, double-blind, three-arm, parallel
      group study compared two doses of fermagate (1 g three times daily or 2 g three
      times daily with placebo). Sixty-three patients who had been on a stable
      hemodialysis regimen for > or =3 mo were randomized to the treatment phase. Study
      medication was administered three times daily just before meals for 21 d. The
      primary endpoint was reduction in serum phosphate over this period. RESULTS: In
      the intention-to-treat analysis, mean baseline serum phosphate was 2.16 mmol/L.
      The fermagate 1- and 2-g three-times-daily treatment arms were associated with
      statistical reductions in mean serum phosphate to 1.71 and 1.47 mmol/L,
      respectively. Adverse event (AE) incidence in the 1-g fermagate arm was
      statistically comparable to the placebo group. The 2-g arm was associated with a
      statistically higher number of patients reporting AEs than the 1-g arm,
      particularly gastrointestinal AEs, as well as a higher number of
      discontinuations, complicating interpretation of this dose's efficacy. Both doses
      were associated with elevations of prehemodialysis serum magnesium levels.
      CONCLUSIONS: The efficacy and tolerability of fermagate were dose dependent.
      Fermagate showed promising efficacy in the treatment of hyperphosphatemia in
      chronic hemodialysis patients as compared with placebo in this initial phase II
      study. The optimal balance between efficacy and tolerability needs to be
      determined from future dose-titration studies, or fixed-dose comparisons of more
      doses.

PMID- 19158370
TI  - High prevalence of intracranial artery calcification in stroke patients with CKD:
      a retrospective study.
AB  - BACKGROUND AND OBJECTIVES: Intracranial artery calcification (IAC) is frequently
      observed on brain computed tomography (CT) scans in stroke patients. This
      retrospective study was designed to determine the prevalence, risk factors, and
      clinical relevance of IAC in a cohort of patients with ischemic stroke. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: We included all eligible patients admitted
      to Amiens University Hospital for acute ischemic stroke between January and
      December 2006 and assessed using 64-slice multidetector-row CT (n = 340).
      Patients were classified according to the presence or absence of IAC in the
      internal carotid arteries, middle cerebral arteries, vertebral arteries, and
      basilar artery. GFR was estimated using the MDRD equation. Chronic kidney disease
      (CKD) was defined as a GFR < 60 ml/min/1.73 m(2). We also studied a control group
      of patients admitted for neurologic diseases other than stroke. RESULTS: Two
      hundred fifty-nine stroke patients (76.2%) displayed IAC, which was independently
      associated with carotid atherosclerosis > 50%, age, and GFR. One hundred three
      nonstroke patients (60.2%) had IAC, with age, arterial hypertension, and GFR as
      independently associated factors. For all patients taken together, age, arterial
      hypertension, stroke, and GFR were independently associated with IAC. CONCLUSION:
      These results confirm the high prevalence of IAC in patients with and without
      ischemic stroke and show for the first time that IAC is associated with the
      presence of CKD in these patients. The frequency of IAC was significantly higher
      in stroke patients than in nonstroke patients. The association between IAC and
      stroke outcome requires further investigation.

PMID- 19158371
TI  - Electrocardiography and outcome in patients with diabetes mellitus on maintenance
      hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: In hemodialysis, applicable guidelines recommend
      regular electrocardiogram (ECG) recordings. However, respective systematic
      evaluations are absent. Thus, the authors investigated whether routine ECG
      findings add prognostic information to standard risk assessment in hemodialysis.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The relationship between nine
      common baseline ECG variables and a combined cardiovascular endpoint (CVE;
      cardiac death, myocardial infarction, stroke), sudden death, stroke, MI, and all
      cause death in 1253 patients from the German Diabetes and Dialysis Study was
      evaluated. All patients were on maintenance hemodialysis, had type 2 diabetes
      mellitus, and received randomized treatment with atorvastatin or placebo.
      RESULTS: During 4 yr of follow-up (March 1998 to March 2004), 469 patients
      reached the CVE, and 617 died. After adjustment for demographics, comorbidities,
      and biomarkers in multivariate analysis, patients presenting without sinus rhythm
      were 89% more likely to die, and the risk of CVE and stroke increased by 75% and
      164%, respectively, compared with patients with preserved sinus rhythm. Left
      ventricular hypertrophy was associated with >2-fold increase in the risk of
      stroke and a 60% increase in the risk of sudden death. CONCLUSIONS: In
      hemodialysis patients with type 2 diabetes mellitus, the absence of sinus rhythm
      is a risk indicator for CVE, stroke, and all-cause death, and left ventricular
      hypertrophy is associated with stroke and sudden death. Thus, routine ECG
      recording adds prognostic information to standard risk assessment.

PMID- 19158372
TI  - Low bone volume--a risk factor for coronary calcifications in hemodialysis
      patients.
AB  - BACKGROUND AND OBJECTIVES: There is increasing evidence that altered bone
      metabolism is associated with cardiovascular calcifications in patients with
      stage 5 chronic kidney disease on hemodialysis (HD). This study was conducted to
      evaluate the association between bone volume, turnover, and coronary
      calcifications in HD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In
      a cross-sectional study, bone biopsies and multislice computed tomography were
      performed in 38 HD patients. Bone volume/total volume, activation frequency, and
      bone formation rate/bone surface were determined by histomorphometry and coronary
      calcifications were quantified by Agatston scores. RESULTS: Prevalence of low
      bone turnover was 50% and of low bone volume was 16%. Among the studied
      traditional cardiovascular risk factors, only age was found to be associated with
      coronary calcifications. Lower bone volume was a significant risk factor for
      coronary calcifications during early years of HD, whereas this effect was not
      observed in patients with dialysis duration >6 yr. Histomorphometric parameters
      of bone turnover were not associated with coronary calcifications. CONCLUSIONS:
      Low bone volume is associated with increased coronary calcifications in patients
      on HD.

PMID- 19158373
TI  - Evidence for pathogenicity of atypical splice mutations in autosomal dominant
      polycystic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Mutation-based molecular diagnostics of autosomal
      dominant polycystic kidney disease (ADPKD) is complicated by locus and allelic
      heterogeneity, large multi-exon gene structure and duplication in PKD1, and a
      high level of unclassified variants. Comprehensive screening of PKD1 and PKD2 by
      two recent studies have shown that atypical splice mutations account for 3.5% to
      5% of ADPKD. We evaluated the role of bioinformatic prediction of atypical splice
      mutations and determined the pathogenicity of an atypical PKD2 splice variant
      from a multiplex ADPKD (TOR101) family. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Using PubMed, we identified 17 atypical PKD1 and PKD2 splice
      mutations. We found that bioinformatics analysis was often useful for evaluating
      the pathogenicity of these mutations, although RT-PCR is needed to provide the
      definitive proof. RESULTS: Sequencing of both PKD1 and PKD2 in an affected
      subject of TOR101 failed to identify a definite mutation, but revealed several
      UCVs, including an atypical PKD2 splice variant. Linkage analysis with
      microsatellite markers indicated that TOR101 was PKD2-linked and IVS8 + 5G-->A
      was shown to cosegregate only with affected subjects. RT-PCR of leukocyte mRNA
      from an affected subject using primers from exons 7 and 9 revealed six splice
      variants that resulted from activation of different combinations of donor and
      acceptor cryptic splice sites, all terminating with premature stop codons.
      CONCLUSIONS: The data provide strong evidence that IVS8 + 5G-->A is a pathogenic
      mutation for PKD2. This case highlights the importance of functional analysis of
      UCVs.

PMID- 19158374
TI  - SCAMP3 negatively regulates epidermal growth factor receptor degradation and
      promotes receptor recycling.
AB  - The epidermal growth factor receptor (EGFR) is targeted for lysosomal degradation
      by ubiquitin-mediated interactions with the ESCRTs (endosomal-sorting complexes
      required for transport) in multivesicular bodies (MVBs). We show that secretory
      carrier membrane protein, SCAMP3, localizes in part to early endosomes and
      negatively regulates EGFR degradation through processes that involve its
      ubiquitylation and interactions with ESCRTs. SCAMP3 is multimonoubiquitylated and
      is able to associate with Nedd4 HECT ubiquitin ligases and the ESCRT-I subunit
      Tsg101 via its PY and PSAP motifs, respectively. SCAMP3 also associates with the
      ESCRT-0 subunit Hrs. Depletion of SCAMP3 in HeLa cells by inhibitory RNA
      accelerated degradation of EGFR and EGF while inhibiting recycling. Conversely,
      overexpression enhanced EGFR recycling unless ubiquitylatable lysines, PY or PSAP
      motifs in SCAMP3 were mutated. Notably, dual depletions of SCAMP3 and ESCRT
      subunits suggest that SCAMP3 has a distinct function in parallel with the ESCRTs
      that regulates receptor degradation. This function may affect trafficking of
      receptors from prelysosomal compartments as SCAMP3 depletion appeared to sustain
      the incidence of EGFR-containing MVBs detected by immunoelectron microscopy.
      Together, our results suggest that SCAMP3, its modification with ubiquitin, and
      its interactions with ESCRTs coordinately regulate endosomal pathways and affect
      the efficiency of receptor down-regulation.

PMID- 19158375
TI  - Role of the tumor suppressor PTEN in antioxidant responsive element-mediated
      transcription and associated histone modifications.
AB  - Coordinated regulation of PI3-kinase (PI3K) and the tumor suppressor phosphatase
      and tensin homologue deleted on chromosome 10 (PTEN) plays a pivotal role in
      various cell functions. PTEN is deficient in many cancer cells, including Jurkat
      human leukemia. Here, we demonstrate that the status of PTEN determines cellular
      susceptibility to oxidative stress through antioxidant-responsive element (ARE)
      mediated transcription of detoxification genes. We found that ferritin H
      transcription was robustly induced in tert-butylhydroquinone (t-BHQ)-treated
      Jurkat cells via an ARE, and it was due to PTEN deficiency. Chromatin
      immunoprecipitation assays revealed that p300/CREB-binding protein (CBP) histone
      acetyltransferases and Nrf2 recruitment to the ARE and Bach1 release were blocked
      by the PI3K inhibitor LY294002, along with the partial inhibition of Nrf2 nuclear
      accumulation. Furthermore, acetylations of histone H3 Lys9 and Lys18, and
      deacetylation of Lys14 were associated with the PI3K-dependent ARE activation.
      Consistently, PTEN restoration in Jurkat cells inhibited t-BHQ-mediated
      expression of ferritin H and another ARE-regulated gene NAD(P)H:quinone
      oxidoreductase 1. Conversely, PTEN knockdown in K562 cells enhanced the response
      to t-BHQ. The PTEN status under t-BHQ treatment affected hydrogen peroxide
      mediated caspase-3 cleavage. The PI3K-dependent ferritin H induction was observed
      by treatment with other ARE-activating agents ethoxyquin and hemin. Collectively,
      the status of PTEN determines chromatin modifications leading to ARE activation.

PMID- 19158376
TI  - ADAMs 10 and 17 represent differentially regulated components of a general
      shedding machinery for membrane proteins such as transforming growth factor
      alpha, L-selectin, and tumor necrosis factor alpha.
AB  - Protein ectodomain shedding is a critical regulator of many membrane proteins,
      including epidermal growth factor receptor-ligands and tumor necrosis factor
      (TNF)-alpha, providing a strong incentive to define the responsible sheddases.
      Previous studies identified ADAM17 as principal sheddase for transforming growth
      factor (TGF)-alpha and heparin-binding epidermal growth factor, but Ca++ influx
      activated an additional sheddase for these epidermal growth factor receptor
      ligands in Adam17-/- cells. Here, we show that Ca++ influx and stimulation of the
      P2X7R signaling pathway activate ADAM10 as sheddase of many ADAM17 substrates in
      Adam17-/- fibroblasts and primary B cells. Importantly, although ADAM10 can shed
      all substrates of ADAM17 tested here in Adam17-/- cells, acute treatment of wild
      type cells with a highly selective ADAM17 inhibitor (SP26) showed that ADAM17 is
      nevertheless the principal sheddase when both ADAMs 10 and 17 are present.
      However, chronic treatment of wild-type cells with SP26 promoted processing of
      ADAM17 substrates by ADAM10, thus generating conditions such as in Adam17-/-
      cells. These results have general implications for understanding the substrate
      selectivity of two major cellular sheddases, ADAMs 10 and 17.

PMID- 19158377
TI  - A primary role for Golgi positioning in directed secretion, cell polarity, and
      wound healing.
AB  - Peri-centrosomal positioning of the mammalian Golgi apparatus is known to involve
      microtubule-based motility, but its importance for cellular physiology is a major
      unanswered question. Here, we identify golgin-160 and GMAP210 as proteins
      required for centripetal motility of Golgi membranes. In the absence of either
      golgin, peri-centrosomal positioning of the Golgi apparatus was disrupted while
      the cytoskeleton remained intact. Although secretion persisted with normal
      kinetics, it was evenly distributed in response to wounding rather than directed
      to the wound edge. Strikingly, these cells also completely failed to polarize.
      Further, directionally persistent cell migration was inhibited such that wound
      closure was impaired. These findings not only reveal novel roles for golgin-160
      and GMAP210 in conferring membrane motility but also indicate that Golgi
      positioning has an active role in directed secretion, cell polarity, and wound
      healing.

PMID- 19158378
TI  - Myosin 2 maintains an open exocytic fusion pore in secretory epithelial cells.
AB  - Many studies have implicated F-actin and myosin 2 in the control of regulated
      secretion. Most recently, evidence suggests a role for the microfilament network
      in regulating the postfusion events of vesicle dynamics. This is of potential
      importance as postfusion behavior can influence the loss of vesicle content and
      may provide a new target for drug therapy. We have investigated the role of
      myosin 2 in regulating exocytosis in secretory epithelial cells by using novel
      assays to determine the behavior of the fusion pore in individual granules. We
      immunolocalize myosin 2A to the apical region of pancreatic acinar cells,
      suggesting it is this isoform that plays a role in granule exocytosis. We further
      show myosin 2 phosphorylation increased on cell stimulation, consistent with a
      regulatory role in secretion. Importantly, in a single-cell, single-granule
      secretion assay, neither the myosin 2 inhibitor (-)-blebbistatin nor the myosin
      light chain kinase inhibitor ML-9 had any effect on the numbers of granules
      stimulated to fuse after cell stimulation. These data indicate that myosin 2, if
      it has any action on secretion, must be targeting postfusion granule behavior.
      This interpretation is supported by direct study of fusion pore opening in which
      we show that (-)-blebbistatin and ML-9 promote fusion pore closure and decrease
      fusion pore lifetimes. Our work now adds to a growing body of evidence showing
      that myosin 2 is an essential regulator of postfusion granule behavior. In
      particular, in the case of the secretory epithelial cells, myosin 2 activity is
      necessary to maintain fusion pore opening.

PMID- 19158379
TI  - Kinesin-5-dependent poleward flux and spindle length control in Drosophila embryo
      mitosis.
AB  - We used antibody microinjection and genetic manipulations to dissect the various
      roles of the homotetrameric kinesin-5, KLP61F, in astral, centrosome-controlled
      Drosophila embryo spindles and to test the hypothesis that it slides apart
      interpolar (ip) microtubules (MT), thereby controlling poleward flux and spindle
      length. In wild-type and Ncd null mutant embryos, anti-KLP61F dissociated the
      motor from spindles, producing a spatial gradient in the KLP61F content of
      different spindles, which was visible in KLP61F-GFP transgenic embryos. The
      resulting mitotic defects, supported by gene dosage experiments and time-lapse
      microscopy of living klp61f mutants, reveal that, after NEB, KLP61F drives
      persistent MT bundling and the outward sliding of antiparallel MTs, thereby
      contributing to several processes that all appear insensitive to cortical
      disruption. KLP61F activity contributes to the poleward flux of both ipMTs and
      kinetochore MTs and to the length of the metaphase spindle. KLP61F activity
      maintains the prometaphase spindle by antagonizing Ncd and another unknown force
      generator and drives anaphase B, although the rate of spindle elongation is
      relatively insensitive to the motor's concentration. Finally, KLP61F activity
      contributes to normal chromosome congression, kinetochore spacing, and anaphase A
      rates. Thus, a KLP61F-driven sliding filament mechanism contributes to multiple
      aspects of mitosis in this system.

PMID- 19158380
TI  - Nbl1p: a Borealin/Dasra/CSC-1-like protein essential for Aurora/Ipl1 complex
      function and integrity in Saccharomyces cerevisiae.
AB  - The Aurora kinase complex, also called the chromosomal passenger complex (CPC),
      is essential for faithful chromosome segregation and completion of cell division.
      In Fungi and Animalia, this complex consists of the kinase Aurora B/AIR-2/Ipl1p,
      INCENP/ICP-1/Sli15p, and Survivin/BIR-1/Bir1p. A fourth subunit,
      Borealin/Dasra/CSC-1, is required for CPC targeting to centromeres and central
      spindles and has only been found in Animalia. Here we identified a new core
      component of the CPC in budding yeast, Nbl1p. NBL1 is essential for viability and
      nbl1 mutations cause chromosome missegregation and lagging chromosomes. Nbl1p
      colocalizes and copurifies with the CPC, and it is essential for CPC
      localization, stability, integrity, and function. Nbl1p is related to the N
      terminus of Borealin/Dasra/CSC-1 and is similarly involved in connecting the
      other CPC subunits. Distant homology searching identified nearly 200, mostly
      unannotated, Borealin/Dasra/CSC-1-related proteins from nearly 150 species within
      Fungi and Animalia. Analysis of the sequence of these proteins, combined with
      comparative protein structure modeling of Bir1p-Nbl1p-Sli15p using the crystal
      structure of the human Survivin-Borealin-INCENP complex, revealed a striking
      structural conservation across a broad range of species. Our biological and
      computational analyses therefore establish that the fundamental design of the CPC
      is conserved from Fungi to Animalia.

PMID- 19158381
TI  - MCAK and paclitaxel have differential effects on spindle microtubule organization
      and dynamics.
AB  - Within the mitotic spindle, there are multiple populations of microtubules with
      different turnover dynamics, but how these different dynamics are maintained is
      not fully understood. MCAK is a member of the kinesin-13 family of microtubule
      destabilizing enzymes that is required for proper establishment and maintenance
      of the spindle. Using quantitative immunofluorescence and fluorescence recovery
      after photobleaching, we compared the differences in spindle organization caused
      by global suppression of microtubule dynamics, by treating cells with low levels
      of paclitaxel, versus specific perturbation of spindle microtubule subsets by
      MCAK inhibition. Paclitaxel treatment caused a disruption in spindle microtubule
      organization marked by a significant increase in microtubules near the poles and
      a reduction in K-fiber fluorescence intensity. This was correlated with a faster
      t(1/2) of both spindle and K-fiber microtubules. In contrast, MCAK inhibition
      caused a dramatic reorganization of spindle microtubules with a significant
      increase in astral microtubules and reduction in K-fiber fluorescence intensity,
      which correlated with a slower t(1/2) of K-fibers but no change in the t(1/2) of
      spindle microtubules. Our data support the model that MCAK perturbs spindle
      organization by acting preferentially on a subset of microtubules, and they
      support the overall hypothesis that microtubule dynamics is differentially
      regulated in the spindle.

PMID- 19158382
TI  - The WASP homologue Las17 activates the novel actin-regulatory activity of Ysc84
      to promote endocytosis in yeast.
AB  - Actin plays an essential role in many eukaryotic cellular processes, including
      motility, generation of polarity, and membrane trafficking. Actin function in
      these roles is regulated by association with proteins that affect its
      polymerization state, dynamics, and organization. Numerous proteins have been
      shown to localize with cortical patches of yeast actin during endocytosis, but
      the role of many of these proteins remains poorly understood. Here, we reveal
      that the yeast protein Ysc84 represents a new class of actin-binding proteins,
      conserved from yeast to humans. It contains a novel N-terminal actin-binding
      domain termed Ysc84 actin binding (YAB), which can bind and bundle actin
      filaments. Intriguingly, full-length Ysc84 alone does not bind to actin, but
      binding can be activated by a specific motif within the polyproline region of the
      yeast WASP homologue Las17. We also identify a new monomeric actin-binding site
      on Las17. Together, the polyproline region of Las17 and Ysc84 can promote actin
      polymerization. Using live cell imaging, kinetics of assembly and disassembly of
      proteins at the endocytic site were analyzed and reveal that loss of Ysc84 and
      its homologue Lsb3 decrease inward movement of vesicles consistent with a role in
      actin polymerization during endocytosis.

PMID- 19158383
TI  - The hydrophobic cysteine-rich domain of SNAP25 couples with downstream residues
      to mediate membrane interactions and recognition by DHHC palmitoyl transferases.
AB  - SNAP25 is synthesized as a soluble protein but must associate with the plasma
      membrane to function in exocytosis; however, this membrane-targeting pathway is
      poorly defined. SNAP25 contains a palmitoylated cysteine-rich domain with four
      cysteines, and we show that coexpression of specific DHHC palmitoyl transferases
      is sufficient to promote SNAP25 membrane association in HEK293 cells. siRNA
      mediated knockdown of its SNARE partner, syntaxin 1A, does not affect membrane
      interaction of SNAP25 in PC12 cells, whereas specific cysteine-to-alanine
      mutations perturb membrane binding, which is restored by leucine substitutions.
      These results suggest a role for cysteine hydrophobicity in initial membrane
      interactions of SNAP25, and indeed other hydrophobic residues in the cysteine
      rich domain are also important for membrane binding. In addition to the cysteine
      rich domain, proline-117 is also essential for SNAP25 membrane binding, and
      experiments in HEK293 cells revealed that mutation of this residue inhibits
      membrane binding induced by coexpression with DHHC17, but not DHHC3 or DHHC7.
      These results suggest a model whereby SNAP25 interacts autonomously with
      membranes via its hydrophobic cysteine-rich domain, requiring only sufficient
      expression of partner DHHC proteins for stable membrane binding. The role of
      proline-117 in SNAP25 palmitoylation is one of the first descriptions of elements
      within substrate proteins that modulate DHHC specificity.

PMID- 19158384
TI  - RACK-1 directs dynactin-dependent RAB-11 endosomal recycling during mitosis in
      Caenorhabditis elegans.
AB  - Membrane trafficking pathways are necessary for the addition and removal of
      membrane during cytokinesis. In animal cells, recycling endosomes act as a major
      source of the additional membranes during furrow progression and abscission.
      However, the mechanisms and factors that regulate recycling endosomes during the
      cell cycle remain poorly understood. Here, we show that the Caenorhabditis
      elegans Receptor of Activated C Kinase 1 (RACK-1) is required for cytokinesis,
      germline membrane organization, and the recruitment of RAB-11-labeled recycling
      endosomes to the pericentrosomal region and spindle. RACK-1 is also required for
      proper chromosome separation and astral microtubule length. RACK-1 localizes to
      the centrosomes, kinetochores, the midbody, and nuclear envelopes during the cell
      cycle. We found that RACK-1 directly binds to DNC-2, the C. elegans p50/dynamitin
      subunit of the dynactin complex. Last, RACK-1 may facilitate the sequestration of
      recycling endosomes by targeting DNC-2 to centrosomes and the spindle. Our
      findings suggest a mechanism by which RACK-1 directs the dynactin-dependent
      redistribution of recycling endosomes during the cell cycle, thus ensuring proper
      membrane trafficking events during cytokinesis.

PMID- 19158385
TI  - Visualization of distinct entities of the SecYEG translocon during translocation
      and integration of bacterial proteins.
AB  - The universally conserved SecYEG/Sec61 translocon constitutes the major protein
      conducting channel in the cytoplasmic membrane of bacteria and the endoplasmic
      reticulum membrane of eukaryotes. It is engaged in both translocating secretory
      proteins across the membrane as well as in integrating membrane proteins into the
      lipid phase of the membrane. In the current study we have detected distinct
      SecYEG translocon complexes in native Escherichia coli membranes. Blue-Native
      PAGE revealed the presence of a 200-kDa SecYEG complex in resting membranes. When
      the SecA-dependent secretory protein pOmpA was trapped inside the SecYEG channel,
      a smaller SecY-containing complex of approximately 140-kDa was observed, which
      probably corresponds to a monomeric SecYEG-substrate complex. Trapping the SRP
      dependent polytopic membrane protein mannitol permease in the SecYEG translocon,
      resulted in two complexes of 250 and 600 kDa, each containing both SecY and the
      translocon-associated membrane protein YidC. The appearance of both complexes was
      correlated with the number of transmembrane domains that were exposed during
      targeting of mannitol permease to the membrane. These results suggest that the
      assembly or the stability of the bacterial SecYEG translocon is influenced by the
      substrate that needs to be transported.

PMID- 19158386
TI  - The nucleoporin Nup153 has separable roles in both early mitotic progression and
      the resolution of mitosis.
AB  - Accurate inheritance of genomic content during cell division is dependent on
      synchronized changes in cellular organization and chromosome dynamics.
      Elucidating how these events are coordinated is necessary for a complete
      understanding of cell proliferation. Previous in vitro studies have suggested
      that the nuclear pore protein Nup153 is a good candidate for participating in
      mitotic coordination. To decipher whether this is the case in mammalian somatic
      cells, we reduced the levels of Nup153 in HeLa cells and monitored consequences
      on cell growth. Reduction of Nup153 resulted in a delay during the late stages of
      mitosis accompanied by an increase in unresolved midbodies. Depletion of Nup153
      to an even lower threshold led to a pronounced defect early in mitosis and an
      accumulation of cells with multilobed nuclei. Although global nucleocytoplasmic
      transport was not significantly altered under these depletion conditions, the FG
      rich region of Nup153 was required to rescue defects in late mitosis. Thus, this
      motif may play a specialized role as cells exit mitosis. Rescue of the multilobed
      nuclei phenotype, in contrast, was independent of the FG-domain, revealing two
      separable roles for Nup153 in the execution of mitosis.

PMID- 19158387
TI  - RNA interference screen identifies Usp18 as a regulator of epidermal growth
      factor receptor synthesis.
AB  - Elevated expression of epidermal growth factor receptor (EGFR) contributes to the
      progression of many types of cancer. Therefore, we developed a high-throughput
      screen to identify proteins that regulate the levels of EGFR in squamous cell
      carcinoma. Knocking down various ubiquitination-related genes with small
      interfering RNAs led to the identification of several novel genes involved in
      this process. One of these genes, Usp18, is a member of the ubiquitin-specific
      protease family. We found that knockdown of Usp18 in several cell lines reduced
      expression levels of EGFR by 50-80%, whereas the levels of other receptor
      tyrosine kinases remained unchanged. Overexpression of Usp18 elevated EGFR levels
      in a manner requiring the catalytic cysteine of Usp18. Analysis of metabolically
      radiolabeled cells showed that the rate of EGFR protein synthesis was reduced up
      to fourfold in the absence of Usp18. Interestingly, this dramatic reduction
      occurred despite no change in the levels of EGFR mRNA. This suggests that
      depletion of Usp18 inhibited EGFR mRNA translation. In fact, this inhibition
      required the presence of native 5' and 3' untranslated region sequences on EGFR
      mRNA. Together, our data provide evidence for the novel mechanism of EGFR
      regulation at the translational step of receptor synthesis.

PMID- 19158388
TI  - Esc2 and Sgs1 act in functionally distinct branches of the homologous
      recombination repair pathway in Saccharomyces cerevisiae.
AB  - Esc2 is a member of the RENi family of SUMO-like domain proteins and is
      implicated in gene silencing in Saccharomyces cerevisiae. Here, we identify a
      dual role for Esc2 during S-phase in mediating both intra-S-phase DNA damage
      checkpoint signaling and preventing the accumulation of Rad51-dependent
      homologous recombination repair (HRR) intermediates. These roles are
      qualitatively similar to those of Sgs1, the yeast ortholog of the human Bloom's
      syndrome protein, BLM. However, whereas mutation of either ESC2 or SGS1 leads to
      the accumulation of unprocessed HRR intermediates in the presence of MMS, the
      accumulation of these structures in esc2 (but not sgs1) mutants is entirely
      dependent on Mph1, a protein that shows structural similarity to the Fanconi
      anemia group M protein (FANCM). In the absence of both Esc2 and Sgs1, the intra-S
      phase DNA damage checkpoint response is compromised after exposure to MMS, and
      sgs1esc2 cells attempt to undergo mitosis with unprocessed HRR intermediates. We
      propose a model whereby Esc2 acts in an Mph1-dependent process, separately from
      Sgs1, to influence the repair/tolerance of MMS-induced lesions during S-phase.

PMID- 19158389
TI  - The Saccharomyces cerevisiae Esc2 and Smc5-6 proteins promote sister chromatid
      junction-mediated intra-S repair.
AB  - Recombination is important for DNA repair, but it can also contribute to genome
      rearrangements. RecQ helicases, including yeast Sgs1 and human BLM, safeguard
      genome integrity through their functions in DNA recombination. Sgs1 prevents the
      accumulation of Rad51-dependent sister chromatid junctions at damaged replication
      forks, and its functionality seems to be regulated by Ubc9- and Mms21-dependent
      sumoylation. We show that mutations in Smc5-6 and Esc2 also lead to an
      accumulation of recombinogenic structures at damaged replication forks. Because
      Smc5-6 is sumoylated in an Mms21-dependent manner, this finding suggests that
      Smc5-6 may be a crucial target of Mms21 implicated in this process. Our data
      reveal that Smc5-6 and Esc2 are required to tolerate DNA damage and that their
      functionality is critical in genotoxic conditions in the absence of Sgs1. As
      reported previously for Sgs1 and Smc5-6, we find that Esc2 physically interacts
      with Ubc9 and SUMO. This interaction is correlated with the ability of Esc2 to
      promote DNA damage tolerance. Collectively, these data suggest that Esc2 and Smc5
      6 act in concert with Sgs1 to prevent the accumulation of recombinogenic
      structures at damaged replication forks, likely by integrating sumoylation
      activities to regulate the repair pathways in response to damaged DNA.

PMID- 19158390
TI  - The two SAS-6 homologs in Tetrahymena thermophila have distinct functions in
      basal body assembly.
AB  - Cilia and flagella are structurally and functionally conserved organelles present
      in basal as well as higher eukaryotes. The assembly of cilia requires a
      microtubule based scaffold called a basal body. The ninefold symmetry
      characteristic of basal bodies and the structurally similar centriole is
      organized around a hub and spoke structure termed the cartwheel. To date, SAS-6
      is one of the two clearly conserved components of the cartwheel. In some
      organisms, overexpression of SAS-6 causes the formation of supernumerary
      centrioles. We questioned whether the centriole assembly initiation capacity of
      SAS-6 is separate from or directly related to its structural role at the
      cartwheel. To address this question we used Tetrahymena thermophila, which
      expresses two SAS-6 homologues, TtSAS6a and TtSAS6b. Cells lacking either TtSAS6a
      or TtSAS6b are defective in new basal body assembly. TtSas6a localizes to all
      basal bodies equally, whereas TtSas6b is enriched at unciliated and assembling
      basal bodies. Interestingly, overexpression of TtSAS6b but not TtSAS6a, led to
      the assembly of clusters of new basal bodies in abnormal locations. Our data
      suggest a model where TtSAS6a and TtSAS6b have diverged such that TtSAS6a acts as
      a structural component of basal bodies, whereas TtSAS6b influences the location
      of new basal body assembly.

PMID- 19158391
TI  - Caveolin-2 is required for apical lipid trafficking and suppresses basolateral
      recycling defects in the intestine of Caenorhabditis elegans.
AB  - Caveolins are plasma membrane-associated proteins that colocalize with, and
      stabilize caveolae. Their functions remain unclear although they are known to be
      involved in specific events in cell signaling and endocytosis. Caenorhabditis
      elegans encodes two caveolin genes, cav-1 and cav-2. We show that cav-2 is
      expressed in the intestine where it is localized to the apical membrane and in
      intracellular bodies. Using the styryl dye FM4-64 and BODIPY-labeled
      lactosylceramide, we show that the intestinal cells of cav-2 animals are
      defective in the apical uptake of lipid markers. These results suggest parallels
      with the function of caveolins in lipid homeostasis in mammals. We also show that
      CAV-2 depletion suppresses the abnormal accumulation of vacuoles that result from
      defective basolateral recycling in rme-1 and rab-10 mutants. Analysis of
      fluorescent markers of basolateral endocytosis and recycling suggest that
      endocytosis is normal in cav-2 mutants and thus, that the suppression of
      basolateral recycling defects in cav-2 mutants is due to changes in intracellular
      trafficking pathways. Finally, cav-2 mutants also have abnormal trafficking of
      yolk proteins. Taken together, these data indicate that caveolin-2 is an integral
      component of the trafficking network in the intestinal cells of C. elegans.

PMID- 19158392
TI  - Fine tuning the cell cycle: activation of the Cdk1 inhibitory phosphorylation
      pathway during mitotic exit.
AB  - Inactivation of cyclin-dependent kinase (Cdk) 1 promotes exit from mitosis and
      establishes G1. Proteolysis of cyclin B is the major known mechanism that turns
      off Cdk1 during mitotic exit. Here, we show that mitotic exit also activates
      pathways that catalyze inhibitory phosphorylation of Cdk1, a mechanism previously
      known to repress Cdk1 only during S and G2 phases of the cell cycle. We present
      evidence that down-regulation of Cdk1 activates Wee1 and Myt1 kinases and
      inhibits Cdc25 phosphatase during the M to G1 transition. If cyclin B/Cdk1
      complex is present in G1, the inhibitory sites on Cdk1 become phosphorylated.
      Exit from mitosis induced by chemical Cdk inhibition can be reversed if cyclin B
      is preserved. However, this reversibility decreases with time after mitotic exit
      despite the continued presence of the cyclin. We show that this G1 block is due
      to phosphorylation of Cdk1 on inhibitory residues T14 and Y15. Chemical
      inhibition of Wee1 and Myt1 or expression of Cdk1 phosphorylation site mutants
      allows reversal to M phase even from late G1. This late Cdk1 reactivation often
      results in caspase-dependent cell death. Thus, in G1, the Cdk inhibitory
      phosphorylation pathway is functional and can lock Cdk1 in the inactive state.

PMID- 19158393
TI  - Phosphatidylinositol-4-phosphate 5-kinase 1alpha mediates extracellular calcium
      induced keratinocyte differentiation.
AB  - Extracellular calcium (Cao) is a major regulator of keratinocyte differentiation,
      but the mechanism is unclear. Phosphatidylinositol-4-phosphate 5-kinase 1alpha
      (PIP5K1alpha) is critical in synthesizing phosphatidylinositol 4,5-bisphosphate
      [PI(4,5)P2]. In this study, we sought to determine whether PIP5K1alpha plays a
      role in mediating the ability of Cao to induce keratinocyte differentiation. We
      found that treatment of human keratinocytes in culture with Cao resulted in
      increased PIP5K1alpha level and activity, as well as PI(4,5)P2 level, binding of
      phosphatidylinositol 3,4,5-triphosphate [PI(3,4,5)P3] to and activation of
      phospholipase C-gamma1 (PLC-gamma1), with the resultant increase in inositol
      1,4,5-trisphosphate (IP3) and intracellular calcium (Cai). Knockdown of
      PIP5K1alpha in human keratinocytes blocked Cao-induced increases in the binding
      of PI(3,4,5)P3 to PLC-gamma1; PLC-gamma1 activity; levels of PI(4,5)P2, IP3, and
      Cai; and induction of keratinocyte differentiation markers. Coimmunoprecipitation
      and confocal studies revealed that Cao stimulated PIP5K1alpha recruitment to the
      E-cadherin-catenin complex in the plasma membrane. Knockdown of E-cadherin or
      beta-catenin blocked Cao-induced activation of PIP5K1alpha. These results
      indicate that after Cao stimulation PIP5K1alpha is recruited by the E-cadherin
      catenin complex to the plasma membrane where it provides the substrate PI(4,5)P2
      for both PI3K and PLC-gamma1. This signaling pathway is critical for Cao-induced
      generation of the second messengers IP3 and Cai and keratinocyte differentiation.

PMID- 19158394
TI  - Microtubule and cell contact dependency of ER-bound PTP1B localization in growth
      cones.
AB  - PTP1B is an ER-bound protein tyrosine phosphatase implied in the regulation of
      cell adhesion. Here we investigated mechanisms involved in the positioning and
      dynamics of PTP1B in axonal growth cones and evaluated the role of this enzyme in
      axons. In growth cones, PTP1B consistently localizes in the central domain, and
      occasionally at the peripheral region and filopodia. Live imaging of GFP-PTP1B
      reveals dynamic excursions of fingerlike processes within the peripheral region
      and filopodia. PTP1B and GFP-PTP1B colocalize with ER markers and coalign with
      microtubules at the peripheral region and redistribute to the base of the growth
      cone after treatment with nocodazole, a condition that is reversible. Growth cone
      contact with cellular targets is accompanied by invasion of PTP1B and stable
      microtubules in the peripheral region aligned with the contact axis. Functional
      impairment of PTP1B causes retardation of axon elongation, as well as reduction
      of growth cone filopodia lifetime and Src activity. Our results highlight the
      role of microtubules and cell contacts in the positioning of ER-bound PTP1B to
      the peripheral region of growth cones, which may be required for the positive
      role of PTP1B in axon elongation, filopodia stabilization, and Src activity.

PMID- 19158395
TI  - Coilin is essential for Cajal body organization in Drosophila melanogaster.
AB  - Cajal bodies (CBs) are nuclear organelles that occur in a variety of organisms,
      including vertebrates, insects, and plants. They are most often identified with
      antibodies against the marker protein coilin. Because the amino acid sequence of
      coilin is not strongly conserved evolutionarily, coilin orthologues have been
      difficult to recognize by homology search. Here, we report the identification of
      Drosophila melanogaster coilin and describe its distribution in tissues of the
      fly. Surprisingly, we found coilin not only in CBs but also in histone locus
      bodies (HLBs), calling into question the use of coilin as an exclusive marker for
      CBs. We analyzed two null mutants in the coilin gene and a piggyBac insertion
      mutant, which leads to specific loss of coilin from the germline. All three
      mutants are homozygous viable and fertile. Cells that lack coilin also lack
      distinct foci of other CB markers, including fibrillarin, the survival motor
      neuron (SMN) protein, U2 small nuclear RNA (snRNA), U5 snRNA, and the small CB
      specific (sca) RNA U85. However, HLBs are not obviously affected in coilin-null
      flies. Thus, coilin is required for normal CB organization in Drosophila but is
      not essential for viability or production of functional gametes.

PMID- 19158396
TI  - The dioxin receptor regulates the constitutive expression of the vav3 proto
      oncogene and modulates cell shape and adhesion.
AB  - The dioxin receptor (AhR) modulates cell plasticity and migration, although the
      signaling involved remains unknown. Here, we report a mechanism that integrates
      AhR into these cytoskeleton-related functions. Immortalized and mouse embryonic
      fibroblasts lacking AhR (AhR-/-) had increased cell area due to spread cytoplasms
      that reverted to wild-type morphology upon AhR re-expression. The AhR-null
      phenotype included increased F-actin stress fibers, depolarized focal adhesions,
      and enhanced spreading and adhesion. The cytoskeleton alterations of AhR-/- cells
      were due to down-regulation of constitutive Vav3 expression, a guanosine
      diphosphate/guanosine triphosphate exchange factor for Rho/Rac GTPases and a
      novel transcriptional target of AhR. AhR was recruited to the vav3 promoter and
      maintained constitutive mRNA expression in a ligand-independent manner.
      Consistently, AhR-/- fibroblasts had reduced Rac1 activity and increased
      activation of the RhoA/Rho kinase (Rock) pathway. Pharmacological inhibition of
      Rac1 shifted AhR+/+ fibroblasts to the null phenotype, whereas Rock inhibition
      changed AhR-null cells to the AhR+/+ morphology. Knockdown of vav3 transcripts by
      small interfering RNA induced cytoskeleton defects and changes in adhesion and
      spreading mimicking those of AhR-null cells. Moreover, vav3-/- MEFs, as AhR-/-
      mouse embryonic fibroblasts, had increased cell area and enhanced stress fibers.
      By modulating Vav3-dependent signaling, AhR could regulate cell shape, adhesion,
      and migration under physiological conditions and, perhaps, in certain
      pathological states.

PMID- 19158397
TI  - The chaperone activity of GRP94 toward insulin-like growth factor II is necessary
      for the stress response to serum deprivation.
AB  - Insulin-like growth factor (IGF)-II is a hormone with mitogenic activity for many
      cell types and tissues. We demonstrate that its intracellular processing and
      secretion strictly depend on the endoplasmic reticulum chaperone glucose
      regulated protein (GRP) 94. GRP94 interacts physically and transiently with pro
      IGF-II intermediates, and its activity is essential for secretion of active IGF
      II, thus establishing IGF-II as a client of GRP94. Embryonic stem (ES) cells that
      lack GRP94 are hypersensitive to stress conditions such as serum deprivation and
      die by apoptosis because they cannot respond to the stress by producing active
      IGF-II. This chaperone-client interaction may explain the previously documented
      antiapoptotic activity of GRP94 in a number of stress responses.

PMID- 19158398
TI  - The SM protein Car/Vps33A regulates SNARE-mediated trafficking to lysosomes and
      lysosome-related organelles.
AB  - The SM proteins Vps33A and Vps33B are believed to act in membrane fusions in
      endosomal pathways, but their specific roles are controversial. In Drosophila,
      Vps33A is the product of the carnation (car) gene. We generated a null allele of
      car to test its requirement for trafficking to different organelles. Complete
      loss of car function is lethal during larval development. Eye-specific loss of
      Car causes late, light-independent degeneration of photoreceptor cells. Earlier
      in these cells, two distinct phenotypes were detected. In young adults,
      autophagosomes amassed indicating that their fusion with lysosomes requires Car.
      In eye discs, endocytosed receptors and ligands accumulate in Rab7-positive
      prelysosomal compartments. The requirement of Car for late endosome-to-lysosome
      fusion in imaginal discs is specific as early endosomes are unaffected.
      Furthermore, lysosomal delivery is not restored by expression of dVps33B. This
      specificity reflects the distinct pattern of binding to different Syntaxins in
      vitro: dVps33B predominantly binds the early endosomal Avl and Car to
      dSyntaxin16. Consistent with a role in Car-mediated fusion, dSyntaxin16 is not
      restricted to Golgi membranes but also present on lysosomes.

PMID- 19158399
TI  - Renal NHE3 and NaPi2 partition into distinct membrane domains.
AB  - Hypertension provokes differential trafficking of the renal proximal tubule
      Na(+)/H(+) exchanger 3 (NHE3) to the base of the apical microvilli and Na(+)-P(i)
      cotransporter 2 (NaPi2) to endosomes. The resultant diuresis and natriuresis are
      key to blood pressure control. We tested the hypothesis that this differential
      trafficking of NHE3 vs. NaPi2 was associated with partitioning to distinct
      membrane domains. In anesthetized rats, arterial pressure was increased (104 +/-
      2 to 142 +/- 4 mmHg, 15 min) by arterial constriction and urine output increased
      23-fold. Renal membranes were fractionated by cold 1% Triton X-100 extraction
      then centrifugation through OptiPrep flotation gradients. In controls, 84 +/- 9%
      of NHE3 localized to flotillin-enriched lipid raft domains and 69 +/- 5% of NaPi2
      localized to transferrin receptor-enriched nonrafts. MyosinVI and dipeptidyl
      peptidase IV, associated with NHE3 regulation, coenriched in lipid rafts with
      NHE3, while NHE regulatory factor-1 coenriched in nonrafts with NaPi2.
      Partitioning was not altered by hypertension. Detergent insoluble membranes were
      pelleted after detergent extraction. NHE3 detergent insolubility decreased as it
      redistributed from body (80 +/- 10% detergent insoluble) to base (75 +/- 3%) of
      the apical microvilli, while NaPi2 partitioned into more insoluble domains as it
      moved from the microvilli (45 +/- 7% detergent insoluble) to endosomes (82 +/-
      1%). In conclusion, NHE3 and NaPi2, while both localized to apical microvilli,
      are segregated into domains: NHE3 to lipid rafts and NaPi2 to nonrafts. These
      domain properties may play a role in the distinct trafficking patterns observed
      during elevated pressures: NHE3 remains in rafts and settles to the base of the
      microvilli while NaPi2 is freely endocytosed.

PMID- 19158400
TI  - Insights into the residence in lipid rafts of adenylyl cyclase AC8 and its
      regulation by capacitative calcium entry.
AB  - Adenylyl cyclases (ACs) are a family of critically important signaling molecules
      that are regulated by multiple pathways. Adenylyl cyclase 8 (AC8) is a Ca(2+)
      stimulated isoform that displays a selective regulation by capacitative Ca(2+)
      entry (CCE), the process whereby the entry of Ca(2+) into cells is triggered by
      the emptying of intracellular stores. This selectivity was believed to be
      achieved through the localization of AC8 in lipid raft microdomains, along with
      components of the CCE apparatus. In the present study, we show that an intact
      leucine zipper motif is required for the efficient N-linked glycosylation of AC8,
      and that this N-linked glycosylation is important to target AC8 into lipid rafts.
      Disruption of the leucine zipper by site-directed mutagenesis results in the
      elimination of N-glycosylated forms and their exclusion from lipid rafts. Mutants
      of AC8 that cannot be N-glycosylated are not demonstrably associated with rafts,
      although they can still be regulated by CCE; however, raft integrity is required
      for the regulation of these mutants. These findings suggest that raft localized
      proteins in addition to AC8 are needed to mediate its regulation by CCE.

PMID- 19158401
TI  - A role for calcium-calmodulin in regulating nitric oxide production during
      skeletal muscle satellite cell activation.
AB  - When skeletal muscle is stretched or injured, myogenic satellite cells are
      activated to enter the cell cycle. This process depends on nitric oxide (NO)
      production by NO synthase (NOS), matrix metalloproteinase activation, release of
      hepatocyte growth factor (HGF) from the extracellular matrix, and presentation of
      HGF to the c-met receptor as demonstrated by a primary culture and in vivo
      assays. We now add evidence that calcium-calmodulin is involved in the satellite
      cell activation cascade in vitro. Conditioned medium from cultures that were
      treated with a calcium ionophore (A23187, ionomycin) for 2 h activated cultured
      satellite cells and contained active HGF, similar to the effect of mechanical
      stretch or NO donor treatments. The response was abolished by addition of
      calmodulin inhibitors (calmidazolium, W-13, W-12) or a NOS inhibitor N(G)-nitro-l
      arginine methyl ester hydrochloride but not by its less inactive enantiomer N(G)
      nitro-d-arginine methyl ester hydrochloride. Satellite cells were also shown to
      express functional calmodulin protein having a calcium-binding activity at 12 h
      postplating, which is the time at which the calcium ionophore was added in this
      study and the stretch treatment was applied in our previous experiments.
      Therefore, results from these experiments provide an additional insight that
      calcium-calmodulin mediates HGF release from the matrix and that this step in the
      activation pathway is upstream from NO synthesis.

PMID- 19158402
TI  - G(s)alpha deficiency in skeletal muscle leads to reduced muscle mass, fiber-type
      switching, and glucose intolerance without insulin resistance or deficiency.
AB  - The ubiquitously expressed G protein alpha-subunit G(s)alpha is required for
      receptor-stimulated intracellular cAMP responses and is an important regulator of
      energy and glucose metabolism. We have generated skeletal muscle-specific
      G(s)alpha-knockout (KO) mice (MGsKO) by mating G(s)alpha-floxed mice with muscle
      creatine kinase-cre transgenic mice. MGsKO mice had normal body weight and
      composition, and their serum glucose, insulin, free fatty acid, and triglyceride
      levels were similar to that of controls. However, MGsKO mice were glucose
      intolerant despite the fact that insulin sensitivity and glucose-stimulated
      insulin secretion were normal, suggesting an insulin-independent mechanism.
      Isolated muscles from MGsKO mice had increased basal glucose uptake and normal
      responses to a stimulator of AMP-activated protein kinase (AMPK), which indicates
      that AMPK and its downstream pathways are intact. Compared with control mice,
      MGsKO mice had reduced muscle mass with decreased cross-sectional area and force
      production. In addition, adult MGsKO mice showed an increased proportion of type
      I (slow-twitch, oxidative) fibers based on kinetic properties and myosin heavy
      chain isoforms, despite the fact that these muscles had reduced expression of
      peroxisome proliferator-activated receptor coactivator protein-1alpha (PGC
      1alpha) and reduced mitochondrial content and oxidative capacity. Therefore
      G(s)alpha deficiency led to fast-to-slow fiber-type switching, which appeared to
      be dissociated from the expected change in oxidative capacity. MGsKO mice are a
      valuable model for future studies of the role of G(s)alpha signaling pathways in
      skeletal muscle adaptation and their effects on whole body metabolism.

PMID- 19158403
TI  - L-Thyroxine vs. 3,5,3'-triiodo-L-thyronine and cell proliferation: activation of
      mitogen-activated protein kinase and phosphatidylinositol 3-kinase.
AB  - 3,5,3'-Triiodo-l-thyronine (T(3)), but not l-thyroxine (T(4)), activated Src
      kinase and, downstream, phosphatidylinositol 3-kinase (PI3-kinase) by means of an
      alpha(v)beta(3) integrin receptor on human glioblastoma U-87 MG cells. Although
      both T(3) and T(4) stimulated extracellular signal-regulated kinase (ERK) 1/2,
      activated ERK1/2 did not contribute to T(3)-induced Src kinase or PI3-kinase
      activation, and an inhibitor of PI3-kinase, LY-294002, did not block activation
      of ERK1/2 by physiological concentrations of T(3) and T(4). Thus the PI3-kinase,
      Src kinase, and ERK1/2 signaling cascades are parallel pathways in T(3)-treated U
      87 MG cells. T(3) and T(4) both caused proliferation of U-87 MG cells; these
      effects were blocked by the ERK1/2 inhibitor PD-98059 but not by LY-294002. Small
      interfering RNA knockdown of PI3-kinase confirmed that PI3-kinase was not
      involved in the proliferative action of T(3) on U-87 MG cells. PI3-kinase
      dependent actions of T(3) in these cells included shuttling of nuclear thyroid
      hormone receptor-alpha (TRalpha) from cytoplasm to nucleus and accumulation of
      hypoxia-inducible factor (HIF)-1alpha mRNA; LY-294002 inhibited these actions.
      Results of studies involving alpha(v)beta(3) receptor antagonists
      tetraiodothyroacetic acid (tetrac) and Arg-Gly-Asp (RGD) peptide, together with
      mathematical modeling of the kinetics of displacement of radiolabeled T(3) from
      the integrin by unlabeled T(3) and by unlabeled T(4), are consistent with the
      presence of two iodothyronine receptor domains on the integrin. A model proposes
      that one site binds T(3) exclusively, activates PI3-kinase via Src kinase, and
      stimulates TRalpha trafficking and HIF-1alpha gene expression. Tetrac and RGD
      peptide both inhibit T(3) action at this site. The second site binds T(4) and
      T(3), and, via this receptor, the iodothyronines stimulate ERK1/2-dependent tumor
      cell proliferation. T(3) action here is inhibited by tetrac alone, but the effect
      of T(4) is blocked by both tetrac and the RGD peptide.

PMID- 19158404
TI  - Phospholemman regulates cardiac Na+/Ca2+ exchanger by interacting with the
      exchanger's proximal linker domain.
AB  - Phospholemman (PLM) belongs to the FXYD family of small ion transport regulators.
      When phosphorylated at Ser(68), PLM inhibits cardiac Na(+)/Ca(2+) exchanger
      (NCX1). We previously demonstrated that the cytoplasmic tail of PLM interacts
      with the proximal intracellular loop (residues 218-358), but not the
      transmembrane (residues 1-217 and 765-938) or Ca(2+)-binding (residues 371-508)
      domains, of NCX1. In this study, we used intact Na(+)/Ca(2+) exchanger with
      various deletions in the intracellular loop to map the interaction sites with
      PLM. We first demonstrated by Western blotting and confocal immunofluorescence
      microscopy that wild-type (WT) NCX1 and its deletion mutants were expressed in
      transfected HEK-293 cells. Cotransfection with PLM and NCX1 (or its deletion
      mutants) in HEK-293 cells did not decrease expression of NCX1 (or its deletion
      mutants). Coexpression of PLM with WT NCX1 inhibited NCX1 current (I(NaCa)).
      Deletion of residues 240-679, 265-373, 250-300, or 300-373 from WT NCX1 resulted
      in loss of inhibition of I(NaCa) by PLM. Inhibition of I(NaCa) by PLM was
      preserved when residues 229-237, 270-300, 328-330, or 330-373 were deleted from
      the intracellular loop of NCX1. These results suggest that PLM mediated
      inhibition of I(NaCa) by interacting with two distinct regions (residues 238-270
      and 300-328) of NCX1. Indeed, I(NaCa) measured in mutants lacking residues 238
      270, 300-328, or 238-270 + 300-328 was not affected by PLM. Glutathione S
      transferase pull-down assays confirmed that PLM bound to fragments corresponding
      to residues 218-371, 218-320, 218-270, 238-371, and 300-373, but not to fragments
      encompassing residues 250-300 and 371-508 of NCX1, indicating that residues 218
      270 and 300-373 physically associated with PLM. Finally, acute regulation of
      I(NaCa) by PLM phosphorylation observed with WT NCX1 was absent in 250-300
      deletion mutant but preserved in 229-237 deletion mutant. We conclude that PLM
      mediates its inhibition of NCX1 by interacting with residues 238-270 and 300-328.

PMID- 19158405
TI  - Acupuncture and exercise restore adipose tissue expression of sympathetic markers
      and improve ovarian morphology in rats with dihydrotestosterone-induced PCOS.
AB  - Altered activity of the sympathetic nervous system, which innervates adipose and
      ovarian tissue, may play a role in polycystic ovary syndrome (PCOS). We
      hypothesize that electro-acupuncture (EA) and physical exercise reduce
      sympathetic activity by stimulating ergoreceptors and somatic afferent pathways
      in muscles. Here we investigated the effects of low-frequency EA and physical
      exercise on mRNA expression of sympathetic markers in adipose tissue and on
      ovarian morphology in female rats that received dihydrotestosterone (DHT)
      continuously, starting before puberty, to induce PCOS. At age 11 wk, rats with
      DHT-induced PCOS were randomly divided into three groups: PCOS, PCOS plus EA, and
      PCOS plus exercise. The latter two groups received 2-Hz EA (evoking muscle
      twitches) three times/week or had free access to a running wheel for 4-5 wk. In
      mesenteric adipose tissue, expression of beta(3)-adrenergic receptor (ADRB3),
      nerve growth factor (NGF), and neuropeptide Y (NPY) mRNA was higher in untreated
      PCOS rats than in controls. Low-frequency EA and exercise downregulated mRNA
      expression of NGF and NPY, and EA also downregulated expression of ADRB3,
      compared with untreated rats with DHT-induced PCOS. EA and exercise improved
      ovarian morphology, as reflected in a higher proportion of healthy antral
      follicles and a thinner theca interna cell layer than in untreated PCOS rats.
      These findings support the theory that increased sympathetic activity contributes
      to the development and maintenance of PCOS and that the effects of EA and
      exercise may be mediated by modulation of sympathetic outflow to the adipose
      tissue and ovaries.

PMID- 19158406
TI  - Galanin microinjection into rostral ventrolateral medulla of the rat is
      hypotensive and attenuates sympathetic chemoreflex.
AB  - Galanin is present in neurons in the brain that are important in the control of
      arterial pressure, and intracisternal administration of galanin evokes
      hypotension, but the site of action is unknown. In urethane-anesthetized,
      vagotomized mechanically ventilated Sprague-Dawley rats (n = 34), we investigated
      the effects of microinjecting galanin (1 mM, 50 nl, 50 pmol) into the rostral
      ventrolateral medulla on resting splanchnic sympathetic nerve activity, arterial
      pressure, heart rate, and phrenic nerve activity. Second, we determined the
      effect of microinjecting galanin into the rostral ventrolateral medulla on the
      cardiovascular response to stimulation of central and peripheral chemoreceptors,
      arterial baroreceptors, and the somatosympathetic reflex. Galanin caused a
      prolonged reduction in resting splanchnic sympathetic nerve activity (-37.0 +/-
      7.2% of baseline), mean arterial pressure (-17.0 +/- 3.5 mmHg), and heart rate (
      25.0 +/- 9.1 beats/min). Galanin increased the sympathoinhibitory response to
      aortic depressor nerve stimulation by 51.8%, had no effect on the
      somatosympathetic reflex, and markedly attenuated the effect of hypercapnia and
      hypoxia on arterial pressure (by 65% and 92.4% of control, respectively). These
      results suggest a role for galanin neurotransmission in the integration of the
      cardiovascular responses to hypoxia, hypercapnia, and the sympathetic baroreflex
      in the rostral ventrolateral medulla. The data suggest that galanin may be an
      important peptide in the homeostatic regulation of chemosensory reflexes.

PMID- 19158407
TI  - T1R2 and T1R3 subunits are individually unnecessary for normal affective licking
      responses to Polycose: implications for saccharide taste receptors in mice.
AB  - The T1R2 and T1R3 proteins are expressed in taste receptor cells and form a
      heterodimer binding with compounds described as sweet by humans. We examined
      whether Polycose taste might be mediated through this heterodimer by testing T1R2
      knockout (KO) and T1R3 KO mice and their wild-type (WT) littermate controls in a
      series of brief-access taste tests (25-min sessions with 5-s trials). Sucrose, Na
      saccharin, and Polycose were each tested for three consecutive sessions with
      order of presentation varied among subgroups in a Latin-Square manner. Both KO
      groups displayed blunted licking responses and initiated significantly fewer
      trials of sucrose and Na-saccharin across a range of concentrations. KO mice
      tested after Polycose exposure demonstrated some degree of concentration
      dependent licking of sucrose, likely attributable to learning related to prior
      postingestive experience. These results are consistent with prior findings in the
      literature, implicating the T1R2+3 heterodimer as the principal taste receptor
      for sweet-tasting ligands, and also provide support for the potential of
      postingestive experience to influence responding in the KO mice. In contrast,
      T1R2 KO and T1R3 KO mice displayed concentration-dependent licking responses to
      Polycose that tracked those of their WT controls and in some cases licked
      midrange concentrations more; the number of Polycose trials initiated overall did
      not differ between KO and WT mice. Thus, the T1R2 and T1R3 proteins are
      individually unnecessary for normal concentration-dependent licking of Polycose
      to be expressed in a brief-access test. Whether at least one of these T1R protein
      subunits is necessary for normal Polycose responsiveness remains untested.
      Alternatively, there may be a novel taste receptor(s) that mediates
      polysaccharide taste.

PMID- 19158409
TI  - Three weeks of postweaning exercise in DIO rats produces prolonged increases in
      central leptin sensitivity and signaling.
AB  - In rats selectively bred to develop diet-induced obesity (DIO) 3 wk of
      postweaning exercise reduces weight and adipose regain for 10 wk after exercise
      cessation, despite intake of 31% fat high-energy (HE) diet. To test the
      hypothesis that this effect is due to increased central leptin sensitivity, 4-wk
      old DIO rats were fed the HE diet and left sedentary (Sed), exercised for 3 wk,
      and then remained sedentary for 10 additional weeks (Ex/Sed) or continued
      exercise for a full 13 wk (Ex). After 3 wk, leptin (5 mg/kg ip) induced a 36%
      decrease in 24-h food intake in Ex rats, while Sed rats had no change in 24-h
      intake. Ex rats also had 23% more leptin-induced phospho-STAT3 (pSTAT3)
      expressing neurons in the arcuate nucleus (ARC) and 95% and 68% higher (125)I
      labeled leptin receptor binding in the ventromedial and dorsomedial nuclei than
      did Sed rats, respectively. At 7 wk after onset, leptin decreased 24-h intake by
      20% in Ex and 24% in Ex/Sed rats without altering Sed intake. After a total of 13
      wk, compared with Sed rats, Ex and Ex/Sed rats had 58% and 38% less fat,
      respectively, but leptin failed to decrease food intake in any group.
      Nevertheless, Ex, but not Ex/Sed rats, still had 32% more ARC leptin-induced
      pSTAT3-expressing neurons than Sed rats. These data suggest that brief
      postweaning exercise in DIO rats that are inherently leptin resistant causes a
      sustained resistance to obesity on HE diet, which is, in part, due to increased
      central leptin sensitivity.

PMID- 19158408
TI  - The pathophysiology of hypertension in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder
      that predominantly affects women during their reproductive years. Although SLE
      can affect any organ system, the kidneys are prominently involved in the form of
      immune complex glomerulonephritis. In addition, in women with SLE, risk for the
      development of cardiovascular disease is dramatically increased. Hypertension is
      a major risk factor for cardiovascular disease and is highly prevalent in women
      with SLE. Nevertheless, there has been little exploration of the
      pathophysiological mechanisms that promote SLE hypertension. This review
      discusses the role of several mechanisms, with an emphasis on the kidney, in SLE
      hypertension. These mechanisms include the renin-angiotensin system, endothelin,
      oxidative stress, sex steroids, metabolic changes, peroxisome proliferator
      activated receptor-gamma, and, perhaps most importantly, chronic inflammation and
      cytokines. Growing evidence suggests a link between chronic inflammation and
      hypertension. Therefore, elucidation of mechanisms that promote SLE hypertension
      may be of significant value not only for patients with SLE, but also for a better
      understanding of the basis for essential hypertension.

PMID- 19158410
TI  - Effects of BDNF, T3, and corticosterone on expression of the hypothalamic obesity
      gene network in vivo and in vitro.
AB  - Hypothalamic neuropeptides, neurotrophins, and systemic hormones modulate food
      intake and body composition. Although advances toward elucidating these
      interactions have been made, many aspects of the underlying mechanisms remain
      vague. Hypothalami from fat and lean chicken lines were assessed for differential
      expression of anabolic/orexigenic and catabolic/anorexigenic genes. Effects of
      triiodothyronine (T(3)), corticosterone (Cort), and brain-derived neurotrophic
      factor (BDNF) on expression of anabolic/orexigenic and catabolic/anorexigenic
      genes were tested in cultures of hypothalamic neurons. From this, we found that
      BDNF increased and T(3) decreased gene expression for BDNF, leptin receptor
      (LEPR), pro-opiomelanocortin (POMC), thyrotropin releasing hormone (TRH), and
      agouti-related protein (AGRP). Thyroid hormone levels were manipulated during
      development to show that T(3) inhibited BDNF, TRH, and BDNF receptor gene
      expression. Delivery of T(3), Cort, T(3) plus Cort, or vehicle in vivo
      continuously for 72 h indicated that Cort and T(3) have overlapping roles in
      regulating TRH, LEPR, and POMC gene expression and that Cort and T(3) regulate
      BDNF, neuropeptide Y, and AGRP in opposite directions. Collectively, these
      findings suggest that interactions between the neuropeptide BDNF and the hormones
      T(3) and/or Cort may constitute a homeostatic mechanism that links hypothalamic
      energy regulation controlling body composition.

PMID- 19158411
TI  - Interstrain variation in cardiac and respiratory adaptation to repeated ozone and
      particulate matter exposures.
AB  - Increased ambient particulate matter (PM) is associated with adverse
      cardiovascular and respiratory outcomes, as demonstrated by epidemiology studies.
      Several studies have investigated the role of copollutants, such as ozone (O(3)),
      in this association. It is accepted that physiological adaptation involving the
      respiratory system occurs with repeated exposures to O(3). We hypothesize that
      adaptation to PM and O(3) varies among different inbred mouse strains, and
      cardiopulmonary adaptation to O(3) is a synchronized response between the cardiac
      and respiratory systems. Heart rate (HR), HR variability (HRV), and the magnitude
      and pattern of breathing were simultaneously measured by implanted telemeters and
      by plethysmography in three inbred mouse strains: C57Bl/6J (B6), C3H/HeJ (HeJ),
      and C3H/HeOuJ (OuJ). Physiological responses were assessed during dual exposures
      to filtered air (FA), O(3) (576 +/- 32 parts/billion), and/or carbon black (CB;
      556 +/- 34 mug/m(3)). Exposures were repeated for 3 consecutive days. While each
      strain showed significant reductions in HR during CB with O(3) preexposure
      (O(3)CB) on day 1, prominent HRV responses were observed in only HeJ and OuJ
      mice. Each strain also differed in their adaptation profile in response to
      repeated O(3)CB exposures. Whereas B6 mice showed rapid adaptation in HR after
      day 1, HeJ mice generally showed more moderate HR and HRV adaptation after day 2
      of exposure. Unlike either B6 or HeJ strains, OuJ mice showed little evidence of
      HR or HRV adaptation to repeated O(3)CB exposure. Adaptation profiles between HR
      regulation and breathing characteristics were strongly correlated, but these
      associations also varied significantly among strains. These findings suggest that
      genetic factors determine the responsivity and adaptation of the cardiac and
      respiratory systems to repeated copollutant exposures. During O(3)CB exposure,
      adaptation of cardiac and respiratory systems is markedly synchronized, which may
      explain a potential mechanism for adverse effects of PM on heart function.

PMID- 19158412
TI  - The prenatal porcine intestine has low transforming growth factor-beta ligand and
      receptor density and shows reduced trophic response to enteral diets.
AB  - Transforming growth factor-beta (TGF-beta) plays a role in enterocyte
      proliferation control, cell differentiation, and immune regulation via binding to
      specific TGF-beta receptors (TGF-beta R) in the intestinal epithelium. Endogenous
      TGF-beta production is low in the intestine during the perinatal period, but some
      exogenous TGF-beta ligands are supplied by amniotic fluid intake in the fetus and
      by colostrum ingestion in the neonate. It is not clear, however, whether luminal
      TGF-beta receptors are present and functional at this critical time. We studied
      intestinal TGF-beta receptors by immunohistochemistry during the last 20% of
      gestation in pigs and in chronically catheterized fetuses following exposure to
      colostrum, milk, and amniotic fluid (control). In fetal pigs, the TGF-beta Rs
      were predominantly localized to the crypt epithelium, but staining intensity
      increased markedly just before term and shifted to the villous epithelium in
      newborn pigs, concurrently with marked increases in villous heights and crypt
      depths (+100-200%, P < 0.05). In contrast to previous observations in term
      newborn pigs, fetal pigs did not show any milk-induced change in TGF-beta
      receptor densities or localization, although a moderate increase in villous
      height was observed, relative to control (+25-50%, P < 0.05). We conclude that
      intestinal TGF-beta receptor density and localization are immature and
      unresponsive to TGF-beta containing milk diets in prenatal pigs. Immaturity of
      TGF-beta-mediated immune regulation may play a role in the increased sensitivity
      of preterm neonates to diet-induced intestinal inflammatory disorders.

PMID- 19158413
TI  - Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets
      during exertional heat stress in trained and untrained individuals.
AB  - This study examined intracellular cytokine, heat shock protein (HSP) 72, and
      cellular apoptosis in classic and inflammatory CD14(+) monocyte subsets during
      exertional heat stress (EHS). Subjects were divided into endurance-trained [TR; n
      = 12, peak aerobic power (Vo(2peak)) = 70 +/- 2 ml.kg lean body mass (LBM)(
      1).min(-1)] and sedentary-untrained (UT; n = 11, Vo(2peak) = 50 +/- 1 ml.kg LBM(
      1).min(-1)) groups before walking at 4.5 km/h with 2% elevation in a climatic
      chamber (40 degrees C, 30% relative humidity) wearing protective clothing until
      exhaustion (Exh). Venous blood samples at baseline and 0.5 degrees C rectal
      temperature increments (38.0, 38.5, 39.0, 39.5, and 40.0 degrees C/Exh) were
      analyzed for cytokines (TNF-alpha, IL-1beta, IL-6, IL-1ra, and IL-10) in
      CD14(++)CD16(-)/CD14(+)CD16(+) and HSP72/apoptosis in CD14(Bri)/CD14(Dim)
      subsets. In addition, serum levels of extracellular (e)HSP72 were also examined.
      Baseline and Exh samples were separately stimulated with LPS (1 microg/ml) or
      heat shocked (42 degrees C) and cultured in vitro for 2 h. A greater temperature
      dependent increase in CD14(+)CD16(+) cells was observed in TR compared with UT
      subjects as well as a greater LPS tolerance following in vitro LPS stimulation.
      TNF-alpha and IL-1beta cytokine expression was elevated in CD14(+)CD16(+) but not
      in CD14(++)CD16(-) cells. A greater induction of intracellular HSP72 and eHSP72
      was observed in TR compared with UT subjects, which coincided with reduced
      apoptosis at Exh and following in vitro heat shock. Induced HSP in vitro was not
      uniform across CD14(+) subsets. Findings suggest that circulating CD14(+)CD16(+),
      but not CD14(++)CD16(-) monocytes, contribute to the proinflammatory cytokine
      profiles observed during EHS. In addition, the enhanced HSP72 response in
      endurance-trained individuals may confer improved heat tolerance through both
      anti-inflammatory and anti-apoptotic mechanisms.

PMID- 19158414
TI  - Efficacy and MRI of rituximab and methotrexate treatment in a nude rat model of
      CNS lymphoma.
AB  - To determine the efficacy of methotrexate and/or rituximab in a CNS lymphoma
      model and to evaluate MRI modalities for monitoring efficacy, we inoculated
      female athymic nude rats (rnu/rnu) intracerebrally with human MC116 B-lymphoma
      cells. Between days 16 and 26, rats were randomized to receive intravenous (IV)
      treatment with (1) saline (controls, n = 15), (2) methotrexate 1,000 mg/m(2) (n =
      6), (3) rituximab 375 mg/m(2) (n = 6), or (4) rituximab plus methotrexate (n =
      6). T2/fluid-attenuated inversion recovery (FLAIR) and gadolinium contrast
      enhanced T1 MRI sequences were performed prior to and 1 week after treatment. IV
      rituximab gave an objective tumor response in four of six animals (>50% reduction
      in tumor volume comparing pre- and posttreatment T2/FLAIR MRI) and resulted in
      stable disease (50%-125% of baseline) in another animal. The percent change in
      tumor volume on T2/FLAIR images was significantly different in the control versus
      rituximab group (p = 0.0051). IV methotrexate slowed tumor growth, compared to
      controls, but only one of six animals had an objective response. In untreated
      controls, tumor histological volumes correlated well with T2/FLAIR or contrast
      enhanced T1 images (r = 0.877). In the treatment groups, T2/FLAIR correlation was
      good, but the gadolinium-enhanced T1 MRI was not significantly correlated with
      histology (r = 0.19). The MC116 CNS lymphoma model seems valuable for preclinical
      testing of efficacy and toxicity of treatment regimens. IV rituximab was highly
      effective, but methotrexate was only minimally effective. T2/FLAIR was superior
      to contrast-enhanced T1 for monitoring efficacy.

PMID- 19158415
TI  - A survey of snake-inspired robot designs.
AB  - Body undulation used by snakes and the physical architecture of a snake body may
      offer significant benefits over typical legged or wheeled locomotion designs in
      certain types of scenarios. A large number of research groups have developed
      snake-inspired robots to exploit these benefits. The purpose of this review is to
      report different types of snake-inspired robot designs and categorize them based
      on their main characteristics. For each category, we discuss their relative
      advantages and disadvantages. This review will assist in familiarizing a newcomer
      to the field with the existing designs and their distinguishing features. We hope
      that by studying existing robots, future designers will be able to create new
      designs by adopting features from successful robots. The review also summarizes
      the design challenges associated with the further advancement of the field and
      deploying snake-inspired robots in practice.

PMID- 19158416
TI  - Synaptic retrogenesis and amyloid-beta in Alzheimer's disease.
AB  - Pathological hallmarks of Alzheimer's disease (AD) include synaptic and neuronal
      degeneration and the presence of extracellular deposits of amyloid-beta (Abeta)
      in senile plaques in the cerebral cortex. Although these brain lesions may be
      seen also in aged non-demented individuals, the increase in brain Abeta is
      believed by many to represent the earliest event in the disease process.
      Accumulating evidence suggests that Abeta, which is highly conserved by
      evolution, may have an important physiological role in synapse elimination during
      brain development. An intriguing idea is that this putative function can become
      pathogenic if activated in the aging brain. Here, we review the literature on the
      possible physiological roles of Abeta and its precursor protein AbetaPP during
      development with special focus on electrophysiological findings.

PMID- 19158417
TI  - Accumulated amyloid-beta peptide and hyperphosphorylated tau protein:
      relationship and links in Alzheimer's disease.
AB  - The neuropathology associated with Alzheimer's disease (AD) is characterized by
      the presence of extracellularly neuritic plaques, intracellularly neurofibrillary
      tangles and the loss of basal forebrain cholinergic neurons. The neuritic plaque
      is composed of a core of amyloid-beta peptide (Abeta) while the neurofibrillary
      tangles contain phosphorylated tau protein, and, as such, both Abeta and tau are
      important molecules associated with AD. In healthy human bodies, clearance
      mechanisms for Abeta are available; yet if clearance fails, Abeta accumulates,
      increasing the risk of neurotoxicity in the brain. Tau, one of the main
      microtubule-associated proteins, will be hyperphosphorylated and lose the ability
      to bind microtubules when the homeostasis of phosphorylation and
      dephosphorylation is disturbed in neurons. Accumulated Abeta and
      hyperphosphorylated tau are thought to be coexistent. Research on the
      pathological changes in AD indicates that accumulated Abeta in vivo may initiate
      the hyperphosphorylation of tau. Also, the signal transduction pathways of tau
      hyperphosphorylation may be related to accumulated Abeta. In this review, we will
      discuss how Abeta accumulates, how tau protein is hyperphosphorylated, and how
      accumulated Abeta initiates hyperphosphorylation of tau protein in AD.

PMID- 19158418
TI  - Acetylcholinesterase inhibitor treatment is associated with relatively slow
      cognitive decline in patients with Alzheimer's disease and AD + DLB.
AB  - Dementia can be caused by different diseases including Alzheimer's disease (AD),
      dementia with Lewy bodies (DLB), or both (AD + DLB). University of Kentucky AD
      Center pathologically-diagnosed AD and AD + DLB cases were evaluated who had
      three or more longitudinal antemortem mental status examinations (n = 156).
      Patients with important concomitant pathology (n = 5) or patients that were
      profoundly demented at recruitment (intake MMSE < 20; n = 86) were excluded to
      strengthen our ability to test the association of specific clinical and
      pathological indices. Patients with pathologically-diagnosed AD + DLB (n = 25)
      lost cognitive capacity faster than patients with AD alone (n = 40). In both
      diseases, treatment with acetylcholinesterase inhibitors was associated with a
      slower rate of cognitive decline.

PMID- 19158420
TI  - Inhibition of autophagy causes tau proteolysis by activating calpain in rat
      brain.
AB  - The autophagic lysosomal system contributes to the removal of cytosolic
      components, and abnormality of lysosomal proteases has been reported in the brain
      of patients with Alzheimer's disease (AD). However, the role of lysosome in tau
      degradation is still elusive. Here, we infused chloroquine, 3-methyladenine or
      rapamycin into rat hippocampus or the lateral ventricle to manipulate the
      autophagic activity and measured the levels of tau protein by Western blotting.
      We unexpectedly observed that the level of different tau species decreased upon
      inhibition of lysosomal proteases or macroautophagy by chloroquine or 3
      methyladenine. Furthermore, induction of autophagic activity by rapamycin did not
      induce degradation of tau proteins. To explore the underlying mechanisms for the
      increased tau degradation induced by autophagic inhibition, we used MG-132, an
      inhibitor of proteasome and calpain. We found that simultaneous inhibition of
      proteasome and calpain by MG-132 prevented the chloroquine-induced tau
      degradation. Further studies demonstrated that the activity of calpain was
      elevated whereas the activity of proteasome was suppressed in response to
      inhibition of autophagy by 3-methyladenine or chloroquine. Our data suggest that
      the lysosomal autophagic system may not degrade tau in the normal adult rat brain
      and inhibition of autophagy may induce tau proteolysis through activating
      calpain.

PMID- 19158419
TI  - Possible Alzheimer's disease in an apolipoprotein E2 homozygote.
AB  - The objective of this study was to describe a case of Alzheimer's disease in an
      ApoE epsilon2/epsilon2 homozygote. ApoE epsilon2/epsilon2 is the rarest of the
      apolipoprotein E genotypes, representing only 1.4% of the population. There is
      only one case reported in the literature of a nonagenarian with minimal cognitive
      changes whose brain showed AD pathology on postmortem study. Here we report an 87
      year-old ApoE epsilon2/epsilon2 female who meets clinical criteria for
      Alzheimer's disease, with confirmation from neuropsychological testing and PET
      scan. Clinical course is typical for Alzheimer's disease with decline on the Mini
      Mental Status Examination from a score of 25 to 19 over 3.5 years. The patient is
      currently treated with donepezil and memantine. In conclusion, a clinically
      confirmed case of Alzheimer's disease is rare in Apo E2 homozygotes but can
      occur.

PMID- 19158421
TI  - Identification of antihypertensive drugs which inhibit amyloid-beta protein
      oligomerization.
AB  - Recent studies suggest that certain cardiovascular antihypertensive agents
      decrease the incidence of Alzheimer's disease. Based on this evidence and the
      fact that Abeta aggregation into high-molecular-weight-soluble oligomeric Abeta
      species is known to directly induce cognitive impairment, we tested the
      possibility that certain antihypertensive compounds may affect the progression of
      Alzheimer's disease, at least in part by influencing the formation of Abeta
      oligomers. High throughput screening of 55 commercially available
      antihypertensive drugs identified four compounds that significantly reduced
      Abeta(1-42) oligomerization in a dose dependent manner. These four compounds,
      furosemide (diuretic), nitrendipine (calcium channel blocker), candesartan
      cilextil (angiotensin II receptor antagonist) and diazoxide (vasodilator) showed
      no detectable Abeta lowering activities in primary neuron cultures generated from
      Tg2576 mouse embryos. However, furosemide, nitrendipine and candesartan cilextil
      prevented oligomerization of both Abeta(1-40) and Abeta(1-42) in vitro.
      Furosemide also dissociated pre-aggregated Abeta(1-42) oligomers. Furthermore,
      short term furosemide treatment resulted in decreased amount of Abeta oligomers
      in the brain of Tg2576 mice. Our studies suggest that certain antihypertensive
      compounds may prevent AD-type neuropathology through inhibition of Abeta oligomer
      formation.

PMID- 19158423
TI  - Integrating gene expression and phenotypic information to analyze Alzheimer's
      disease.
AB  - The assessment of the relationship between gene expression profiling, clinical
      and histopathological phenotypes would be better suited to understanding
      Alzheimer's disease (AD) pathogenesis. We developed a multiple linear regression
      (MLR) method to simultaneously model three variables - Mini-Mental Status
      Examination (MMSE) score, neurofibrillary tangles (NFT) score and gene expression
      profile - to identify significant genes. These genes were also used to
      distinguish subjects with incipient AD from healthy controls. Finally we
      investigated the behavior of the significant genes across the entorhinal cortex
      and hippocampus of AD subjects in two different Braak stages. Results indicate
      that integrating multiple phenotypic and gene expression information of samples
      increases the power of methods while analyzing small datasets. The MLR method
      could identify significant genes at reasonable false discovery rates (FDRs),
      thereby providing a choice of reasonable FDRs. The accuracy in discriminating
      between subjects affected and unaffected by AD using MLR identified genes was
      high. We found that transcription and tumor suppressor responses do begin quite
      early in AD and therefore should be the target of drugs. Several genes were
      consistently up/down-regulated across the two brain regions and Braak stages and,
      therefore, can be used as predictive markers to detect AD at an earlier stage.

PMID- 19158424
TI  - Midlife coffee and tea drinking and the risk of late-life dementia: a population
      based CAIDE study.
AB  - Caffeine stimulates central nervous system on a short term. However, the long
      term impact of caffeine on cognition remains unclear. We aimed to study the
      association between coffee and/or tea consumption at midlife and
      dementia/Alzheimer's disease (AD) risk in late-life. Participants of the
      Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study were randomly
      selected from the survivors of a population-based cohorts previously surveyed
      within the North Karelia Project and the FINMONICA study in 1972, 1977, 1982 or
      1987 (midlife visit). After an average follow-up of 21 years, 1409 individuals
      (71%) aged 65 to 79 completed the re-examination in 1998. A total of 61 cases
      were identified as demented (48 with AD). Coffee drinkers at midlife had lower
      risk of dementia and AD later in life compared with those drinking no or only
      little coffee adjusted for demographic, lifestyle and vascular factors,
      apolipoprotein E epsilon4 allele and depressive symptoms. The lowest risk (65%
      decreased) was found in people who drank 3-5 cups per day. Tea drinking was
      relatively uncommon and was not associated with dementia/AD. Coffee drinking at
      midlife is associated with a decreased risk of dementia/AD later in life. This
      finding might open possibilities for prevention of dementia/AD.

PMID- 19158422
TI  - Heterogeneity in red wine polyphenolic contents differentially influences
      Alzheimer's disease-type neuropathology and cognitive deterioration.
AB  - We recently found that moderate consumption of two unrelated red wines generate
      from different grape species, a Cabernet Sauvignon and a muscadine wine that are
      characterized by distinct component composition of polyphenolic compounds,
      significantly attenuated the development of Alzheimer's disease (AD)-type brain
      pathology and memory deterioration in a transgenic AD mouse model. Interestingly,
      our evidence suggests that the two red wines attenuated AD phenotypes through
      independent mechanisms. In particular, we previously found that treatment with
      Cabernet Sauvignon reduced the generation of AD-type amyloid-beta (Abeta)
      peptides. In contrast, evidence from our present study suggests that muscadine
      treatment attenuates Abeta neuropathology and Abeta-related cognitive
      deterioration in Tg2576 mice by interfering with the oligomerization of Abeta
      molecules to soluble high-molecular-weight Abeta oligomer species that are
      responsible for initiating a cascade of cellular events resulting in cognitive
      decline. Collectively, our observations suggest that distinct polyphenolic
      compounds from red wines may be bioavailable at the organism level and
      beneficially modulate AD phenotypes through multiple Abeta-related mechanisms.
      Results from these studies suggest the possibility of developing a "combination"
      of dietary polyphenolic compounds for AD prevention and/or therapy by modulating
      multiple Abeta-related mechanisms.

PMID- 19158426
TI  - Exonic point mutations of human tau enhance its toxicity and cause characteristic
      changes in neuronal morphology, tau distribution and tau phosphorylation in the
      lamprey cellular model of tauopathy.
AB  - Exonic mutations in the gene coding for human tau cause familial neurofibrillary
      degenerative diseases (tauopathies) which exhibit mutation-specific
      characteristics. It is thus unclear whether such mutations have similar effects
      on tau structure and function in vivo and if they act via similar
      cytopathological mechanisms in vulnerable neuron types. We have previously shown
      that overexpressing wild type human tau isoforms in identified giant neurons
      (ABCs) of the lamprey CNS results in characteristic, stereotyped cytopathological
      changes in these cells over several weeks. Here, we use this model to compare the
      cytopathological consequences of expressing wild type and exonic mutant tau
      isoforms (P301L, G272V, V337M, and R406W) at a high level of resolution. We show
      that each of the four exonic htau mutations tested accelerate degeneration in
      ABCs when compared to their WT parent isoforms, and that the patterns of human
      tau distribution, phosphorylation and cytopathology, while similar, vary
      characteristically from one another among both WT and mutant isoforms in a single
      identified neuron in situ. Our results therefore suggest that at least some of
      the differences between the effects of these mutations in humans are due to cell
      autonomous, mutation specific differences in the cytopathological mechanism of
      tau-induced neurodegeneration.

PMID- 19158427
TI  - Balance features in Alzheimer's disease and amnestic mild cognitive impairment.
AB  - We evaluated alterations of balance by stabilometry in patients with amnestic
      mild cognitive impairment (aMCI) and with mild-moderate Alzheimer's disease (AD).
      Fifteen patients with aMCI and 15 with mild AD were recruited according to the
      current diagnostic criteria. Fifteen healthy subjects of the same age range were
      recruited as controls. Stabilometry was carried out using a commercial 4 load
      cell platform. Statistical analysis of between group differences was performed
      using one-way analysis of variance for parametric data and Kruskal-Wallis tests
      for non-parametric data. Spearman correlation coefficients were used to
      investigate the association between cognitive test scores and stabilometric data.
      All stabilometry measures were significantly altered in mild AD patients compared
      to normal controls. Antero-posterior sway was found to be the most sensitive
      parameter, since it correlated with the ADAS-cog orientation subscale in AD
      patients, and also discriminated between aMCI and normal controls. Our study
      shows that impairment in balance is a feature not only of AD, but also of aMCI.
      The alterations found suggest that a progressive failure of the vestibular
      system, possibly linked to reduced hippocampal performance, may be responsible
      for such a feature. Further research must be focused on studying the predictive
      value of stabilometry in the conversion of aMCI.

PMID- 19158425
TI  - Ascorbic acid and rates of cognitive decline in Alzheimer's disease.
AB  - The brain maintains high levels of ascorbic acid (AA) despite a concentration
      gradient favoring diffusion from brain to peripheral tissues. Dietary
      antioxidants, including AA, appear to modify the risk of Alzheimer's disease
      (AD). The objective of this study was to test the hypothesis that
      neurodegeneration in AD is modified by brain levels of AA. Thirty-two patients
      with mild to moderate AD participated in a biomarker study involving standardized
      clinical assessments over one year. Cerebrospinal fluid (CSF) and serum were
      collected at baseline for AA and albumin content. Cognitive measures were
      collected at baseline and one year. CSF and plasma AA failed to predict cognitive
      decline independently, however, CSF: plasma AA ratio did. After adding CSF
      Albumin Index (an established marker of blood-brain barrier integrity) to the
      regression models the effect of CSF: plasma AA ratio as a predictor of cognitive
      decline was weakened. CSF: plasma AA ratio predicts rate of decline in AD. This
      relationship may indicate that the CSF: plasma AA ratio is an index of AA
      availability to the brain or may be an artifact of a relationship between blood
      brain barrier impairment and neurodegeneration.

PMID- 19158428
TI  - Impact of 27-hydroxycholesterol on amyloid-beta peptide production and ATP
      binding cassette transporter expression in primary human neurons.
AB  - Cholesterol is an integral component of neuronal membranes and recent evidence
      has shown that it regulates amyloid-beta protein precursor processing to form
      amyloid-beta peptides, which are a major constituent of cerebral amyloid plaques
      associated with Alzheimer's disease. 27-Hydroxycholesterol (27OHC) is synthesized
      from cholesterol via sterol 27-hydroxylase (CYP27A1) in the brain and, unlike
      cholesterol, can cross into the brain through the blood brain barrier from the
      circulation. Previous studies point toward a potential role for 27OHC in the
      regulation of neuronal amyloid-beta peptide generation, however, this has not
      been investigated in primary human neurons. Here we show that 27OHC significantly
      reduced amyloid-beta peptide detected in cell culture supernatants from primary
      human neurons. We also show that 27OHC does not affect alpha-, beta- or gamma
      secretase activity but does upregulate the liver X receptor (LXR) responsive
      genes ABCA1, ABCG1 and APOE. These data suggest that 27OHC-mediated reduction in
      extracellular amyloid-beta peptide levels is potentially due to its action as an
      LXR ligand.

PMID- 19158430
TI  - Tau phosphorylation by cdk5 and Fyn in response to amyloid peptide Abeta (25-35):
      involvement of lipid rafts.
AB  - Alzheimer's disease (AD) is characterized by the accumulation of protein
      filaments, namely extracellular amyloid-beta (Abeta) fibrils and intracellular
      neurofibrillary tangles, which are composed of aggregated hyperphosphorylated
      tau. Tau hyperphosphorylation is the product of deregulated Ser/Thr kinases such
      as cdk5 and GSK3beta. In addition, tau hyperphosphorylation also occurs at Tyr
      residues. To find a link between Abeta and tau phosphorylation, we investigated
      the effects of short-term Abeta treatments on SHSY-5Y cells. We analyzed
      phosphorylated tau variants in lipid rafts and the possible role of Tyr18 and
      Ser396/404 tau phosphorylation in Abeta-induced signaling cascades. After 2 min
      of Abeta treatment, phospho-Tyr18-tau and its association with rafts increased.
      Phospho-Ser 396/404-tau became detectable in rafts after 10 min treatment, which
      temporally correlated with the detection of cdk5 and p35 activator in lipid
      rafts. To determine the role of cdk5 in tau phosphorylation at Ser396/404 in
      lipid rafts, we pre-incubated cells with cdk5 inhibitor roscovitine, and observed
      that the Abeta-induced tau phosphorylation at Ser 396/404 in rafts was abolished
      as well as cdk5/p35 association with rafts. These data suggest a role for cdk5 in
      the Abeta-promoted early events involving tau hyperphosphorylation, and their
      possible implications for AD pathogenesis.

PMID- 19158429
TI  - Altering presenilin gene activity in zebrafish embryos causes changes in
      expression of genes with potential involvement in Alzheimer's disease
      pathogenesis.
AB  - Aberrant splicing and point mutations in the human presenilin genes, PSEN1 and
      PSEN2, have been linked to familial forms of Alzheimer's disease. We have
      previously described that low-level aberrant splicing of exon 8 in zebrafish
      psen1 transcripts in zebrafish embryos produces potent dominant negative effects
      that increase psen1 transcription, cause a dramatic hydrocephalus phenotype,
      decreased pigmentation and other developmental defects. Similar effects are also
      observed after low-level interference with splicing of exon 8 of psen2. To
      determine the molecular etiology of these effects, we performed microarray
      analyses of global gene expression changes. Of the 100 genes that showed greatest
      dysregulation after either psen1 or psen2 manipulation, 12 genes were common to
      both treatments. Five of these have known function and showed increased
      expression: cyclin G1 (ccng1), prosaposin (psap), cathepsin Lb (ctslb), heat
      shock protein 70kDa (hsp70) and hatching enzyme 1 (he1). We used phylogenetic and
      conserved synteny analysis to confirm the orthology of zebrafish ccng1 with human
      CCNG1. We analyzed the expression of zebrafish ccng1 in developing embryos to 24
      hours post fertilization (hpf). Decreased ccng1 expression does not rescue the
      hydrocephalus or pigmentation phenotypes of embryos with aberrant splicing of
      psen1 exon 8.

PMID- 19158431
TI  - False recognition correlates with amyloid-beta (1-42) but not with total tau in
      cerebrospinal fluid of patients with dementia and mild cognitive impairment.
AB  - Severe memory impairment forms the core symptom of Alzheimer's disease (AD),
      which is present early in the disease course. Recent studies show that AD
      patients not only suffer from forgetfulness, but also differ in their response
      bias, when having to decide whether information has been perceived recently, or
      whether it is only familiar or semantically related to perceived information.
      Changes in total tau-protein and amyloid-beta (Abeta) (1-42) concentration in
      cerebrospinal fluid are also features of AD, and they predict conversion from
      mild cognitive impairment to dementia. In this study we correlated recognition
      scores with total tau and Abeta (1-42) concentrations in patients with suggested
      dementia. We studied 40 patients and 21 healthy controls, using an incidental
      recognition memory task and a neuropsychological test battery. False recognition
      scores correlated with delayed recall and with Abeta(1-42), and Abeta (1-42)
      tended to correlate with delayed recall. Total tau, however, did not correlate
      with memory scores or with neuropsychological performance in general. We suggest
      that Abeta (1-42) may indicate a reduction in the specificity of the neuronal
      response in the limbic cortex, due to agglomeration of plaques. This process
      might be more specific for AD than the increase of tau, and therefore it is
      stronger correlated with recognition errors.

PMID- 19158432
TI  - Dietary supplementation with apple juice decreases endogenous amyloid-beta levels
      in murine brain.
AB  - Folate deficiency has been associated with age-related neurodegeneration. We
      demonstrate herein that dietary deficiency in folate and vitamin E, coupled pro
      oxidant stress induced by dietary iron, increased amyloid-beta (Abeta) levels in
      normal adult mice. This increase was potentiated by apolipoprotein E (ApoE)
      deficiency as shown by treatment of transgenic mice homozygously lacking murine
      ApoE. Dietary supplementation with apple juice concentrate in drinking water
      alleviated the increase in Abeta for both mouse genotypes. These findings provide
      further evidence linking nutritional and genetic risk factors for age-related
      neurodegeneration, and underscore that dietary supplementation may be useful to
      augment therapeutic approaches.

PMID- 19158433
TI  - Psychotic symptoms in Alzheimer's disease and 5-HTTLPR polymorphism of the
      serotonin transporter gene: evidence for an association.
AB  - The occurrence of psychotic symptoms is common in Alzheimer's disease (AD),
      configuring a possibly distinguished clinical entity defined "Psychosis in
      Alzheimer's Disease" (AD-P). In order to investigate demographic clinical and
      biological variables potentially associated to the occurrence of AD-P, 148 AD
      patients were selected. Mini-Mental State Examination (MMSE), Activities of Daily
      Living (ADL), and Instrumental Activities of Daily Living (IADL) scores, socio
      economic status and 5-HTTLPR and APOE gene polymorphisms were determined for each
      subject. AD-P patients were significantly more frequent carriers of the long (L)
      allele of 5-HTTLPR. The percentage of AD-P increased with the number of copies of
      the L-allele: 13% among S homozygote; 36% among heterozygotes; 51% among L
      homozygotes. No difference resulted between AD-P and non-psychotic AD (AD-NP) in
      the distribution of the epsilon4 allele of APOE. The risk of AD-P was increased
      in L/L homozygous (OR = 7.25, p = 0.003) and, to a lesser extent, in heterozygous
      (OR = 3.91; p = 0.018). Backward logistic regression analysis showed that the
      risk for AD-P was increased in older subjects (OR = 1.07; p = 0.018) while an
      increase of MMSE score was protective (OR = 0.90; p = 0.004). The occurrence of
      AD-P resulted significantly related to age at examination, cognitive status, and
      to the presence of the 5-HTTLPR L-allele.

PMID- 19158434
TI  - Lack of association between interleukin-1 alpha rs1800587 polymorphism and
      Alzheimer's disease in two Independent European samples.
AB  - Interleukin-1 (IL1) can contribute to pathophysiology of Alzheimer's disease (AD)
      by promoting deposition of amyloid-beta in the brain. The gene encoding IL1 alpha
      (IL1A) has a common polymorphism in its 5' regulatory region (rs1800587) with
      possible functional effects. IL1A T/T genotype has been associated with AD but
      the overall effect is modest and negative studies have been published. The aim of
      this study was to investigate the association of the IL1A rs1800587 polymorphism
      with AD in two independent case-control groups from Greece (Athens) and Italy
      (Faenza and Granarolo). Preliminary results from the ongoing sample (110 patients
      with sporadic AD and 130 nonpsychiatric controls) showed no association between
      IL1A variants and AD, however C/T heterozygotes had more severe depression in AD
      (Cornell Scale for Depression in Dementia) compared to other genotypes (F = 4.56,
      d.f = 1, p = 0.037) after controlling for age, illness duration and cognitive
      impairment (MMSE). Despite the small sample size and the possibility of a false
      negative finding, our preliminary data support the hypothesis the IL1A rs1800587
      variants are not associated with AD. The effect of the IL1A on depressive
      symptomatology warrants further investigations, however the lack of a gene-dose
      relationship would suggest a false positive.

PMID- 19158435
TI  - An intraperitoneally administered pentapeptide protects against Abeta (1-42)
      induced neuronal excitation in vivo.
AB  - The underlying cause of Alzheimer's disease (AD) is thought to be the
      accumulation and aggregation of a misfolded protein, amyloid-beta (Abeta). A
      promising strategy against AD is the application of protective, peptide-based
      neuroprotective agents that selectively bind to Abeta. We recently described a
      pentapeptide, LPYFDa, which recognizes Abeta (1-42) and protects neurons against
      the toxic effects of aggregated Abeta (1-42) both in vitro and in vivo. Our
      previous work indicated that the in vivo ejection of fibrillar Abeta (1-42) into
      the hippocampal CA1 region resulted in a massive increase in the NMDA-evoked
      neuronal firing rate. Our current aim was to study whether intraperitoneally
      administered LPYFDa is capable of protecting against the synaptotoxic action of
      fibrillar Abeta (1-42) administered by iontophoresis. Our investigations of the
      in vivo biodistribution of tritium-labelled LPYFDa and single-unit
      electrophysiology revealed that LPYFDa readily crosses the blood-brain barrier,
      and protects the synapses against the excitatory action of fibrillar Abeta (1-42)
      in a relatively wide temporal window in rat. This pentapeptide may serve as a
      lead compound for the design of novel drug candidates for the prevention of AD.

PMID- 19158436
TI  - Alzheimer research forum live discussion: mice on trial? Issues in the design of
      drug studies.

PMID- 19158438
TI  - Implications of measuring soluble receptor activators of nuclear factor-kappaB
      ligand and osteoprotegerin in bone metabolism of elderly women.
AB  - BACKGROUND/AIM: The discovery of a signaling system consisting of a soluble
      receptor activator of the NF-kappaB ligand (sRANKL) and its decoy receptor
      osteoprotegerin (OPG) has provided a valuable key to understanding the
      pathophysiology of the bone microenvironment. We conducted a cross-sectional
      study of the role of sRANKL and OPG levels as they relate to bone metabolism in
      elderly postmenopausal women with and without osteoporosis. SUBJECTS AND METHODS:
      Fifty-one elderly women with or without osteoporosis were enrolled in the study.
      Bone alkaline phosphatase, osteocalcin, urinary deoxypyridinoline and urinary
      type I collagen N-terminal telopeptide (NTx) were measured as bone metabolic
      markers. Serum levels of OPG and sRANKL were measured by sandwich enzyme-linked
      immunosorbent assay and the lumbar spine bone mineral density (LSBMD) with dual
      energy X-ray absorptiometry. Furthermore, we compared the sRANKL and OPG levels
      in elderly women with and without vertebral fractures (VFs). RESULTS: In elderly
      postmenopausal women, there was a significant positive association between OPG
      levels and the T score and Z score of LSBMD (r = 0.345 and p = 0.014 for T score;
      r = 0.438 and p = 0.001 for Z score). sRANKL levels were not significantly
      correlated with T score, Z score of LSBMD, or any of the four bone metabolic
      markers. There were no significant differences in the sRANKL levels among the
      three groups (normal bone mineral density, osteopenia, and osteoporosis), but a
      trend toward a higher value in the osteoporosis group. The sRANKL/OPG ratio was
      negatively correlated with the T score and Z score of LSBMD (r = -0.336, p =
      0.017; r = -0.384, p = 0.006, respectively), but not with any of the four bone
      metabolic markers. OPG levels in elderly women with VFs were lower than in those
      without VFs (p = 0.05). Multiple regression analysis showed that OPG and NTx are
      contributing factors to bone loss in elderly women (p = 0.014 and 0.012,
      respectively). CONCLUSION: The OPG level provides a good predictor of
      osteoporosis as well as NTx in elderly women; additionally, the findings suggest
      that OPG might protect elderly women from bone loss or fractures.

PMID- 19158439
TI  - Amelioration of diabetic nephropathy in OLETF rats by prostaglandin I(2) analog,
      beraprost sodium.
AB  - BACKGROUND: Strict control of blood glucose and blood pressure levels sometimes
      fails to delay the development of diabetic nephropathy, and an effective therapy
      is not yet available. The present study aimed to examine whether the
      prostaglandin I(2) analog beraprost sodium (BPS) ameliorates diabetic nephropathy
      in Otsuka Long-Evans Tokushima Fatty (OLETF) rat. METHOD: Fifty-week-old OLETF
      rats were divided into three groups according to treatment; 400 microg/kg body
      weight (BW) BPS, 200 microg/kg BW BPS, and 0.9% saline administration. Kidney
      histology, index of glomerulosclerosis, and glomerular volume were determined,
      and urine and serum chemistry were assessed. RESULTS: The values for urine
      protein excretion and serum blood urea nitrogen in BPS-treated rats were
      significantly lower than those in untreated rats. In rats treated with 400
      microg/kg BW BPS, neither sclerotic changes nor inflammatory cell infiltration
      were observed. Index of glomerulosclerosis and glomerular volume were also
      significantly reduced compared with untreated rats. Intriguingly, BPS reduced the
      level of serum triglyceride. In the glomerulus of treated rats, advanced
      glycation end product formation and macrophage influx were suppressed in a dose
      dependent manner. CONCLUSION: These findings indicate that BPS has a therapeutic
      effect on diabetic nephropathy in the OLETF rat, which suggests a potential
      application of this drug in the treatment of human diabetic nephropathy.

PMID- 19158441
TI  - Association of cognitive impairment with serum lipid/lipoprotein among Chinese
      nonagenarians and centenarians.
AB  - The association of cognitive impairment with abnormal levels of serum
      lipid/lipoprotein in the elderly, in whom there are differences between the old
      aged 65-84 years and the oldest old aged 85 years or above, has been confirmed by
      previous studies. However, there are no relevant data from a Chinese oldest old
      population. In the present study, we observed an association of cognitive
      impairment with abnormal levels of serum lipid/lipoprotein among very old people
      using a Chinese cohort aged 90-108 years. The population included 709 unrelated
      Chinese nonagenarians and centenarians (67.8% women, mean age 93.8 years). The
      mean score of cognitive function (measured with the 30-item Mini-Mental State
      Examination, MMSE) was 14.9 (SD 6.0). Comparing abnormal with normal levels of
      serum lipid/lipoprotein (including triglycerides, total cholesterol, high-density
      lipoprotein and low-density lipoprotein), in both genders, the odds ratio of
      cognitive impairment was statistically insignificant. There were no significant
      differences in levels of lipid/lipoprotein between subjects with and without
      cognitive impairment. Pearson correlation showed that MMSE scores were not
      significantly correlated with levels of lipid/lipoprotein. In summary, we found
      that levels of serum lipid/lipoprotein were not directly correlated with
      cognitive impairment among Chinese nonagenarians and centenarians.

PMID- 19158440
TI  - Neuroanatomy of apathy and disinhibition in frontotemporal lobar degeneration.
AB  - OBJECTIVE: To investigate the neural basis for the behavioral symptoms of
      frontotemporal lobar degeneration (FTLD) that cause the greatest caregiver
      distress. BACKGROUND: FTLD is a progressive neurodegenerative disease associated
      with behavioral disturbances. Group studies have related these behaviors to
      volume loss on MRI. METHODS: Forty caregivers of patients with the clinical
      diagnosis of FTLD completed the Neuropsychiatric Inventory. Twelve
      neuropsychiatric symptoms and the associated caregiver distress were assessed.
      Optimized voxel-based morphometry identified significant atrophy in subgroups of
      FTLD patients with isolated behavioral symptoms corresponding to the most
      distressing behaviors, and we correlated cortical atrophy directly with these
      distressing behavioral disorders in an unbiased group analysis. RESULTS: The
      greatest stressors for caregivers were apathy and disinhibition (p < 0.005 for
      both contrasts). Partially distinct areas of cortical atrophy were associated
      with these behaviors in both individual patients with these symptoms and group
      wide analyses, including the dorsal anterior cingulate cortex and dorsolateral
      prefrontal cortex in apathetic patients, and the medial orbital frontal cortex in
      disinhibited patients. CONCLUSIONS: Caregiver stress in families of FTLD patients
      is due in large part to apathy and disinhibition. The anatomic distribution of
      cortical loss corresponding to these distressing social behaviors includes
      partially distinct areas within the frontal lobe.

PMID- 19158442
TI  - Molecular evolution of HA1 in influenza A (H3N2) viruses isolated in Japan from
      1989 to 2006.
AB  - OBJECTIVES: To evaluate the trend of phylogenetic evolution among influenza A
      (H3N2) viruses isolated in Gunma and A (H3N2) vaccine strains, we studied the
      transition of gene mutations and amino acid substitution of the sites A and B in
      HA1 during long-term seasons. METHODS: A total of 15 A (H3N2) strains were
      obtained from patients in Gunma, Japan, during the 1989-2006 seasons. A partial
      HA1 gene was amplified by reverse transcription-polymerase chain reaction (RT
      PCR). The phylogenetic tree and amino acid sequences were determined with
      nucleotide sequences. RESULTS: We found that the nucleotide sequences of the
      isolates in the 1989-1990 and 1997-1998 seasons were similar to those of the
      A/Beijing/352/89 and the A/Sydney/5/97 strains, respectively, indicating a lag
      between the circulated virus and the vaccine strains. Phylogenetic analysis made
      possible to classify into two clusters in genetic evolutions among these strains,
      which showed large antigenic conversion. Moreover, we confirmed that basic amino
      acids tended to substitute uncharged polar amino acids, like K135T (lysine-to
      threonine substitution at position 135), K145N, H155T, K156Q, R189S and R197Q, as
      confirmed by multiple alignment of amino acid sequences. CONCLUSIONS: We showed a
      new understanding of genetic evolution and amino acid substitutions of HA1 to
      recur pandemic.

PMID- 19158443
TI  - Neurovascular pulsatile compression and neurosurgical decompression of the
      rostral ventrolateral medulla in medically resistant hypertensive patients.
AB  - BACKGROUND/AIMS: In cases of severe primary hypertension not responding to
      conventional medical therapy, neurovascular pulsatile compression of the rostral
      ventrolateral medulla on the left side may be considered as an etiological factor
      in the hypertension. Through neurosurgical decompression, the blood pressure can
      be reduced in these cases, and the conventional medication can also become more
      effective. METHODS: The authors retrospectively analysed the changes in the blood
      pressure and therapy of patients with or without neurosurgical decompression over
      a 2-year period. The 2-year data were available for 9 operated and 7 non-operated
      patients with neurovascular compression. The data of control examinations
      performed 1, 3, 6, 12 and 24 months after the intervention (or after MR
      angiography in the non-operated cases) were analysed. RESULTS: After the
      decompression, both the systolic and diastolic blood pressure decreased
      significantly and permanently in all cases, and there was an improved response to
      the medication. In the non-operated group, the blood pressure did not change
      significantly during the 2 years. CONCLUSION: In severe hypertension that does
      not respond to conventional therapy, neurosurgical decompression of the brain
      stem on the left side can guarantee a long-lasting blood pressure reduction and a
      better response to antihypertensive medication.

PMID- 19158444
TI  - Cytogenetic analysis of false-positive mucosa by photodynamic diagnosis using 5
      aminolevulinic acid - possible existence of premalignant genomic alterations
      examined by in vitro experiment.
AB  - OBJECTIVE: Although photodynamic diagnosis is a powerful tool for the detection
      of flat urothelial tumors, false-positive fluorescent mucosa still requires
      further elucidation. Thus, we aimed to study the significance of nonmalignant
      fluorescent mucosa by a cytogenetic approach. METHODS: Sixty specimens of bladder
      mucosa were collected from 20 patients who were suspected of having carcinoma in
      situ by fluorescence cystoscopy with 5-aminolevulinic acid. To detect the copy
      number aberrations, the multi-color fluorescence in situ hybridization technique
      was performed, and the variant fractions (total fractions other than those of the
      modal copy number) of chromosomes 7, 9 and 17 and the chromosomal instability
      were determined. To delineate the relevant gene to the fluorescent mucosa, a
      comparative genomic hybridization technique was applied for 8 established bladder
      cancer cell lines, and these results were compared with the in vitro fluorescent
      expression experiment. RESULTS: Fluorescent mucosa was detected in 33 of the 34
      malignant tissue specimens (16 carcinoma in situ, 18 other transitional cell
      carcinomas) and in 11 of the 26 nonmalignant tissue specimens (6 dysplasia, 20
      normal mucosa), with a false-positive rate of 42.3%. The variant fraction of
      chromosome 9 was significantly higher in fluorescent than in non-fluorescent
      mucosa, not only for all tissues (33 vs. 17%; p = 0.0069), but also for
      nonmalignant tissues (28 vs. 15%; p = 0.0225). There was no alteration in
      chromosome 9 in 1 cell line without fluorescent mucosa, while 5 of the 7 cell
      lines with fluorescent mucosa had a common deleted region on 9q24.1. CONCLUSION:
      These data suggest that a substantial portion of nonmalignant fluorescent mucosa
      harbors alterations in chromosome 9.

PMID- 19158445
TI  - Efficacy and safety of S-1 monotherapy in patients with advanced biliary tract
      adenocarcinoma: retrospective analysis of 162 patients.
AB  - AIM: We investigated the efficacy and safety of S-1 monotherapy for the treatment
      of advanced biliary tract adenocarcinoma (BTA) in a clinical practice setting.
      METHODS: We reviewed clinical data from 217 patients with advanced BTA who were
      treated with S-1 monotherapy between August 2004 and September 2007. RESULTS: 162
      eligible patients were identified. The primary tumors were intrahepatic (n = 57),
      in the gall bladder (n = 50), in extrahepatic bile ducts (n = 41) and in the
      ampulla of Vater (n = 14). Sixteen of 120 assessable patients achieved partial
      responses, with a response rate of 13.3% (95% CI 7.2-19.4%). Another 51 patients
      had stable disease, with an overall tumor control rate of 55.8% (95% CI 46.9
      64.7%). The median time to progression was 2.7 months and the median overall
      survival time was 6.9 months. Response rates and survival differed significantly
      according to the primary site of the tumor (p = 0.002 and p < 0.001,
      respectively), with extrahepatic bile duct adenocarcinoma having the best
      prognosis. The treatment regimen produced only mild toxicity in most cases (grade
      1 or 2), even for patients with hyperbilirubinemia. CONCLUSION: S-1 has a
      favorable toxicity profile and can be safely administered to BTA patients with
      hyperbilirubinemia. The efficacy of S-1 against advanced BTA depends on the tumor
      site and is most effective in patients with extrahepatic BTA.

PMID- 19158446
TI  - Breast cancer patients on endocrine therapy reveal more symptoms when self
      reporting than in pivotal trials: an outcome research study.
AB  - OBJECTIVES: The purpose of this investigation was firstly to assess the overall
      frequency of subjectively experienced symptoms self-reported by patients
      receiving endocrine therapy and secondly to compare these symptoms with side
      effects assessed by clinicians in pivotal trials. METHODS: Unselected patients
      with early and advanced breast cancer receiving endocrine therapy were approached
      consecutively during a routine outpatient visit. They received a questionnaire
      called Checklist for Patients with Endocrine Therapy (C-PET), a validated self
      assessment tool to determine prespecified symptoms associated with endocrine
      therapy. Data on toxicity were also obtained from previously published trials.
      RESULTS: 405 patients were approached and 373 agreed to participate in this
      study. Some symptoms were significantly more often recorded by the women in the
      adjuvant setting completing the C-PET than by physicians' reports in pivotal
      trials: hot flushes/sweats (C-PET 70%, ATAC 40% and BIG1-98 38%), low energy (C
      PET 45%, ATAC 15% and BIG1-98 9%), fluid retention (C-PET 22% and BIG1-98 7%) and
      vaginal dryness (C-PET 30% and BIG1-98 3%). Similar differences were observed in
      the metastatic and adjuvant setting. CONCLUSIONS: A simple tool like the C-PET
      questionnaire is able to reflect the treatment burden of endocrine therapies and
      may be helpful to improve communication between patients and care providers. Some
      symptoms were significantly more often reported by the women in the C-PET than by
      physicians in pivotal trials.

PMID- 19158447
TI  - Measurement of pupil centroid shift and cyclotorsional displacement using iris
      registration.
AB  - BACKGROUND/AIMS: To estimate the amount and nature of pupil centroid shift and
      cyclotorsion occurring between preoperative wavefront measurement and refractive
      surgery. METHODS: This retrospective study comprised 183 eyes of 92 patients who
      had wavefront-guided LASIK using iris registration. We analyzed the pupil
      centroid shift and cyclotorsional displacement occurring between preoperative
      wavefront measurements and during the laser procedure. The eyes were measured by
      the WaveScan Wavefront system (VISX, Santa Clara, Calif., USA) and refractive
      surgery was performed with the VISX STAR S4 excimer laser system. RESULTS: The
      mean magnitude of shifts in the location of pupil center was 0.26 +/- 0.16 mm
      horizontally, 0.20 +/- 0.16 mm vertically and 0.37 +/- 0.13 mm vectorally. 162
      eyes (88.5%) experienced more than 0.2 mm of shift. The mean amount of torsion
      was 2.58 +/- 1.56 degrees for 83 eyes showing incyclotorsion and 2.94 +/- 1.87
      degrees for 100 eyes showing excyclotorsion. 117 eyes (63.9%) experienced more
      than 2 degrees of cyclotorsion and 21 eyes (11.5%) experienced more than 5
      degrees of cyclotorsion. CONCLUSIONS: Pupil centroid shift and cyclotorsion occur
      in the majority of eyes undergoing laser treatment. The amount of pupil centroid
      shift and cyclotorsion shown in this study is considerable. Accurate compensation
      for cyclotorsion and pupil centroid shift may maximize the potential of visual
      quality of customized ablations.

PMID- 19158448
TI  - Diffusion-weighted MRI in the diagnosis of cholesteatomas.
AB  - OBJECTIVE: The diagnosis of a cholesteatoma can be difficult in cases with an
      intact tympanic membrane. The aim of our study was to examine whether diffusion
      weighted MRI can confirm the diagnosis of a cholesteatoma. STUDY DESIGN: A
      preoperative diffusion-weighted MRI (echo-planar imaging) scan of the temporal
      bone was performed in 31 patients with clinically suspected cholesteatoma. The
      diagnosis was confirmed by pathohistological examination in 18 cases, while the
      majority of the remaining patients showed chronic otitis media without
      cholesteatoma. RESULTS: In 3 out of 18 patients with histologically confirmed
      cholesteatoma, diffusion-weighted imaging produced a hyperintense signal. Another
      4 of the 18 cases had a questionable positive result. No increased signal was
      observed in 11 of these 18 patients. Of 12 patients without a cholesteatoma, 2
      showed a positive signal while a questionable hyperintense signal was observed in
      5 patients. CONCLUSIONS: According to our present findings, diffusion-weighted
      MRI (echo-planar imaging) can--with a low sensitivity and specificity--be helpful
      in individual cases in provisionally diagnosing a cholesteatoma in association
      with standard MRI and high-resolution CT, even though the lack of a hyperintense
      signal in diffusion-weighted MRI does not exclude a cholesteatoma.

PMID- 19158449
TI  - [Treatment of metacarpal fractures with open reduction and low-profile plate and
      screw fixation].
AB  - OBJECTIVES: We evaluated functional results and effectiveness of open reduction
      and low-profile plate fixation for the treatment of low-severity metacarpal
      fractures. METHODS: We retrospectively reviewed 50 metacarpal fractures of 43
      patients (37 men, 6 women; mean age 31+/-9 years; range 17 to 52 years) who were
      treated with open reduction and low-profile plate fixation. Fractures of the
      first metacarpal were excluded. There were 26 oblique, 12 transverse, and 12
      comminuted fractures. Three fractures were open. Objective assessment included
      total active motion (TARM) and grip strength. Subjective assessment was made
      using the Turkish version of the Quick-DASH scale. Radiographic evaluations were
      made on anteroposterior/lateral and oblique roentgenograms. Complications were
      classified as major or minor according to the Page-Stern system. The mean follow
      up was 62.2+/-24.8 months (range 12 to 96 months). RESULTS: At final evaluations,
      the mean TARM was 220.5+/-43.9 degrees (range 30 degrees to 260 degrees ). The
      results were excellent in 25 patients (58.1%), good in 12 patients (27.9%), fair
      in five patients (11.6%), and poor in one patient (2.3%). The mean loss of grip
      strength was 5.2+/-7.3%. The mean Quick-DASH score was 2.0+/-2.8 (range 0 to 11).
      All fractures were united. Ten patients had major complications (23.2%), which
      included extensor tenosynovitis and plate-related discomfort requiring plate
      removal in four patients (9.3%), and less than 180 degrees of TARM in six
      patients (14%). CONCLUSION: Low-severity metacarpal fractures can be treated
      successfully with open reduction and low-profile plate fixation, allowing early
      and safe functional use.

PMID- 19158450
TI  - [Extramembranous transfer of the tibialis posterior tendon for the correction of
      drop foot deformity].
AB  - OBJECTIVES: We evaluated the effectiveness of extramembranous transfer of the
      tibialis posterior (TP) tendon for the treatment of drop foot deformity. METHODS:
      The study included 13 patients (6 females, 7 males; mean age 30 years; range 10
      to 46 years) who underwent 15 tendon transfers for drop foot deformity. Ten
      patients (76.9%) had deformity due to unrepairable nerve injuries, which were
      associated with surgical procedures in six patients and trauma in the remaining
      four. In four feet (26.7%), the TP tendon was turned from the intero-anterior
      aspect of the tibia and fixed by tenodesis to the lateral cuneiform bone, while
      in 11 feet (73.4%), it was transferred to the extensor hallucis longus, extensor
      digitorum communis, and peroneus tertius tendons. The patients were assessed
      according to the Stanmore system questionnaire. The mean follow-up was 25.3
      months (range 12 to 80 months). RESULTS: According to the Stanmore system, the
      results were poor in two feet (13.3%), moderate in three feet (20%), good in
      three feet, and very good in seven feet (46.7%). All the patients were satisfied
      with the final outcome. The mean foot dorsiflexion was 5 degrees (range, -5
      degrees to 10 degrees ), which was 10 degrees in four feet (26.7%), and 5 degrees
      to 10 degrees in six feet (40%). Apart from complaints of bulging in four
      patients (30.8%) in the dorsum of the foot due to tendon and suture material, no
      complications were seen during the early postoperative period. CONCLUSION:
      Extramembranous transfer of the TP tendon for the treatment of drop foot
      deformity enables the patients to walk without the aid of orthosis and increases
      their quality of life.

PMID- 19158451
TI  - [Proprioception of the knee joint in patellofemoral pain syndrome].
AB  - OBJECTIVES: The importance of proprioception in the etiology, treatment, and
      prevention of sports injuries and joint diseases has become increasingly clear.
      The purpose of this study was to investigate knee proprioception in patients with
      patellofemoral pain syndrome (PFPS). METHODS: The study included 28 patients (18
      females, 10 males; mean age 28 years; range 16 to 48 years) with a clinical
      diagnosis of unilateral PFPS and 27 normal volunteers (13 females, 14 males; mean
      age 26 years; range 19 to 32 years) without any complaint related to the knee.
      The mean duration of complaints was 35.8 weeks (range 2 weeks to 3 years). In
      both patient and control groups, proprioception of the knee was measured by means
      of active joint position sense at four different target angles (15 degrees , 30
      degrees , 45 degrees , 60 degrees ) with the use of a digital goniometer and the
      results were compared. RESULTS: Proprioceptive errors were greater at all target
      angles in the affected knees compared to those measured in the contralateral
      knees and both knees of the controls. Differences between affected knees and
      contralateral knees ranged from 1.01+/-0.25 degrees to 1.65+/-0.43 degrees and
      were significant at three target angles (15 degrees , 30 degrees , 60 degrees ;
      p<0.05). Comparisons between the affected knees and both knees of the controls
      also showed significant differences at all target angles ranging from 2.48+/-0.92
      degrees to 3.87+/-2.46 degrees (p<0.001). Errors obtained in the normal knees of
      the patients were also significantly greater compared to those seen in both knees
      of the controls, exceeding 2.7 degrees at some target angles (p<0.001).
      CONCLUSION: Our results show that patients with PFPS have impaired proprioception
      in the affected knee accompanied by significant losses in the proprioception of
      the contralateral normal knee. Based on these findings, proprioceptive
      rehabilitation techniques should be incorporated into the treatment of PFPS.

PMID- 19158453
TI  - [The prevalence of low back pain and risk factors among adult population in Afyon
      region, Turkey].
AB  - OBJECTIVES: This study was designed to determine the prevalence of and risk
      factors for low back pain (LBP) in a sample of Turkish population among adults
      living in the Afyon region, Turkey. METHODS: A field screening investigation was
      performed in a total of 75 areas including the city center, 18 districts, and 57
      associated small municipalities. Adequate sample size was determined as 1,990 and
      a total of 2,035 individuals (1,194 females, 841 males) were enrolled.
      Participants were inquired about age, occupation, sex, height, weight, history of
      LBP, hypertension, diabetes, and smoking. Depression symptoms were evaluated
      using the Symptom Checklist-90-Revised. RESULTS: The prevalence of lifetime LBP
      was 51%, and the prevalence of chronic LBP was 13.1%. Overall, 63.2% of women and
      33.8% of men had LBP at least once in their lives (p=0.001). With regard to
      occupation, the highest incidence of LBP was seen in housewives (64.2%;
      p=0.0001), whose age and body mass index (BMI) were also higher compared to
      employed women. Depression (p=0.016) and increased BMI (p=0.000) were found to
      increase the risk for LBP, whereas smoking, hypertension, or diabetes were not
      correlated with the prevalence of LBP. Poverty was found to be the leading cause
      (39.7%) for not presenting to a physician. CONCLUSION: Among risk factors
      reported for LBP, many are also effective in Turkish population. Special
      attention should be given to the education of housewives in terms of low back
      protection, healthy nutrition, and family planning. Poverty seems to be a
      significant barrier to patient presentation to physicians, requiring extended
      social security coverage.

PMID- 19158452
TI  - [Venous thromboembolism prophylaxis in major orthopaedic surgery: A multicenter,
      prospective, observational study].
AB  - OBJECTIVES: We investigated risk factors for venous thromboembolism (VTE),
      prophylaxis measures employed, and incidence of symptomatic deep venous
      thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing major
      orthopaedic surgery (MOS). METHODS: An open, multicenter, prospective,
      observational study was conducted in 21 medical centers, comprising 899 patients.
      Of these, 316 patients (35.2%) underwent total hip arthroplasty (THA), 328
      patients (36.5%) underwent total knee arthroplasty (TKA), and 255 patients
      (28.4%) underwent surgery for hip fractures (HF). Pharmacologic prophylaxis was
      employed in all the patients. RESULTS: Risk factors for VTE were seen in 73.2% of
      the patients, the most common being obesity (72%) and prolonged immobilization
      (36.3%). Low-molecular-weight heparin (91.1%) and fondaparinux (8.9%) were used
      for prophylaxis, which was short-term in 273 patients (30.4%) and long-term in
      626 patients (69.6%). Mechanical prophylaxis was performed with compression
      stockings in 610 patients (67.9%) and by intermittent pneumatic compression in 67
      patients (7.5%). During three-months of follow-up, symptomatic DVT and PE were
      seen in eight (0.9%) and four patients (0.4%), respectively. Mortality occurred
      in 10 patients (1.1%). Complications of major and minor bleeding were seen in
      eight (0.9%) and 40 (4.5%) patients, respectively. CONCLUSION: Effective VTE
      prophylaxis is associated with low risk of clinically apparent DVT and PE in MOS.

PMID- 19158454
TI  - [Treatment strategy in tuberculous spondylitis: long-term follow-up results of 55
      patients].
AB  - OBJECTIVES: We evaluated our treatment algorithm used in adult patients with
      tuberculous spondylitis together with long-term treatment results. METHODS: The
      study included 55 adult patients (26 males, 29 females; mean age 50 years; range
      23 to 71 years) with tuberculous spondylitis. The patients underwent four
      different treatment methods including non-operative treatment (NO, 6 patients),
      posterior debridement, fusion and instrumentation (PDFI, 21 patients), anterior
      debridement, instrumentation and fusion (ADIF, 21 patients), and finally, urgent
      radical debridement (RD, 11 patients) due to financial limitations of the
      patients. All the patients received antituberculous therapy for 12 months. On
      presentation, 17 patients (30.9%) had neurologic deficits (ADIF, 6 patients; RD,
      11 patients). Neurologic assessment was made according to the Frankel grading
      system. The results were evaluated with respect to kyphosis, sagittal balance,
      neurologic recovery, and patient satisfaction. The mean follow-up period was 95.3
      months (range 66 to 114 months). RESULTS: Radiographically, successful bone
      fusion was achieved in all the patients. Following treatment, all surgically
      treated groups exhibited decreases in the kyphotic angle. The mean correction was
      significantly greater in ADIF (17.5 degrees ) and PDFI (12.1 degrees ) groups
      compared to the RD group (4.9 degrees ) (p<0.05). Final increases in the kyphotic
      angle were 0.7 degrees , 1.2 degrees , 1.4 degrees , and 1.6 degrees in NO, PDFI,
      ADIF, and RD groups, respectively. The mean sagittal deviations in the first
      postoperative month were +2 mm, +11 mm, +12 mm, and +14 mm in NO, PDFI, ADIF, and
      RD groups, respectively, which remained unchanged till the end of follow-up.
      Complete neurologic recovery was obtained in all but one patient. All the
      patients expressed satisfaction with the treatment. No recurrences or
      reactivation of disease were observed. CONCLUSION: This study showed that, with
      appropriate patient selection, the results of NO, PDFI, and ADIF were
      satisfactory and comparable.

PMID- 19158455
TI  - [Mosaicplasty technique in the treatment of osteochondral lesions of the knee].
AB  - OBJECTIVES: We evaluated early results of patients undergoing mosaicplasty for
      full-thickness cartilage lesions of the knee. METHODS: The study included 24
      patients (8 females, 16 males; mean age 39 years; range 17 to 52 years) with full
      thickness cartilage lesions on the weight-bearing surface of the lateral (n=6)
      and medial (n=8) femoral condyles. Mosaicplasty was performed with open surgery.
      All grafts were harvested from the ipsilateral femoral condyle at the level of
      the sulcus terminalis and transplanted with the mosaicplasty technique to the
      defect area. The mean defect diameter was 13.5 mm (range 8 to 27 mm), and the
      mean number of grafts used was 1.5 (range 1 to 4). Final clinical assessments
      were made using the Lysholm and ICRS (International Cartilage Repair Society)
      scoring systems. Radiological evaluations were made according to the Kellgren
      Lawrence criteria. Donor-site morbidity was evaluated according to the Bandi
      scoring system. The mean follow-up was 30.5 months (range 13 to 47 months).
      RESULTS: The mean pre- and postoperative Lysholm knee scores were 46 (range 28 to
      64) and 86 (range 76 to 100), respectively. ICRS scores were grade I in 16
      patients (66.7%), grade II in six patients (25%), and grade III in two patients
      (8.3%). Five patients (20.8%) had slight donor-site disturbance which regressed
      within six months to a level that did not restrict daily physical activities. All
      the patients returned to preinjury activity levels. Postoperative magnetic
      resonance imaging showed no signs of graft loosening or collapse. According to
      the Kellgren-Lawrence criteria, 20 patients (83.3%) were free from any signs of
      osteoarthritis, whereas four patients (16.7%) exhibited early osteoarthritic
      changes. CONCLUSION: Mosaicplasty is a reliable procedure in the treatment of
      full-thickness chondral lesions because it is minimally invasive, can be
      performed at a single session, and has a low complication rate and low cost.

PMID- 19158456
TI  - [The results of tendon transfer in irreparable radial nerve palsy].
AB  - OBJECTIVES: The purpose of this study was to evaluate the results of tendon
      transfers in patients with irreparable radial nerve palsy. METHODS: The study
      included 29 patients (5 females, 24 males; mean age 29 years; range 9 to 51
      years) who underwent tendon transfers for radial nerve palsy. Four patients had
      low- and 25 patients had high-level radial nerve palsy. The mean duration of
      tendon transfer after injury (paralysis time) was 19.7 months (range 1 day to 180
      months). Clinical evaluations included joint range of motion and muscle
      strengths. Functional evaluation was made using the Tajima criteria. The mean
      follow-up was 56.9 months (range 5 to 90 months). RESULTS: Muscle strengths were
      measured as follows: 3 (n=3), 4 (n=10), and 5 (n=12) for the wrist extensor
      muscle; 3 (n=7), 4 (n=10), and 5 (n=12) for the finger extensor muscle; and 3
      (n=6), 4 (n=13), and 5 (n=10) for the thumb extensor muscle. The mean wrist range
      of motion was 67.4 degrees , extension was 48.3 degrees (10 degrees to 70 degrees
      ), and flexion was 21.5 degrees (10 degrees to 55 degrees ). The mean
      metacarpophalangeal joint extension was 1.7 degrees (0 degrees to 12 degrees ),
      thumb abduction was 45.6 degrees (34 degrees to 56 degrees ), and thumb
      interphalangeal joint extension was 18 degrees (0 degrees to 30 degrees ).
      According to the Tajima criteria, the results were excellent in 15 patients
      (51.7%), good in nine patients (31%), and moderate in five patients (17.2%).
      Eight patients (27.6%) had radial deviation deformity and four patients (13.8%)
      had 1-level weaker finger extensor muscle strength compared to the other fingers.
      The flexor carpi ulnaris (FCU) was used in the transfer of patients who developed
      radial deviation deformity. CONCLUSION: Treatment of irreparable radial nerve
      palsy with tendon transfers yields successful results. Radial deviation deformity
      mostly occurs in patients receiving FCU transfer for finger extension.

PMID- 19158457
TI  - [Southwick osteotomy in stable slipped capital femoral epiphysis: a long-term
      outcome study].
AB  - OBJECTIVES: Moderate to severe chronic stable slipped capital femoral epiphysis
      (SCFE) produce permanent irregularities in the femoral head and acetabulum. We
      report a single centre long-term outcome study of Southwick's procedure for the
      management of moderate or severe stable chronic SCFE with irregularity of the
      femoral head. METHODS: In the period from January 1978 to January 1990, 20
      patients (16 girls, 4 boys; mean age 13 years; range 11 to 15 years) underwent 22
      Southwick osteotomies for chronic stable SCFE with closure or partial closure of
      the growth plate and a slip between 30 degrees and 70 degrees . All osteotomies
      were performed by the same surgeon. Patients were followed-up for an average of
      22 years (range 16 to 28 years). RESULTS: External rotation deformity was
      corrected, and the Trendelenburg sign was hardly observable in any of the
      patients from six months of surgery. Radiographically, all patients showed full
      consolidation of the osteotomy within two months of surgery. There was no further
      epiphyseal slipping. We did not encounter any infection or avascular necrosis.
      Only one patient developed chondrolysis, which resolved fully in eight months. At
      the latest follow-up, no limb length discrepancy was seen in 18 patients, while
      two patients had a mean of 0.8 cm shortening. Eight patients (36.4%) showed
      radiographic evidence for degenerative joint disease, but none were symptomatic.
      CONCLUSION: The management of chronic stable (moderate to severe) SCFE by
      Southwick's osteotomy is safe, but technically demanding. It affords good
      predictable outcome with a low complication rate.

PMID- 19158459
TI  - [A case of multiple congenital anomalies including agenesis of the anterior
      cruciate ligament].
AB  - Congenital absence of the anterior cruciate ligament (ACL) is a very rare
      anomaly. It is usually diagnosed during arthroscopic intervention. We presented a
      15-year old male patient whose diagnosis was based on findings of physical
      examination and magnetic resonance imaging. Congenital absence of the ACL was
      associated with femoral shortening, dysplasia of the tibial intercondylar
      eminence, valgus knee, and compensatory scoliosis. Since the patient had no
      instability symptoms, and due to the presence of a negative pivot-shift test and
      multiple congenital anomalies, surgical treatment was not considered.

PMID- 19158458
TI  - [Comparison between fixation with dorsal T plate and palmar locking plate in the
      treatment of unstable displaced distal radius fractures].
AB  - OBJECTIVES: We compared the results of fixation with dorsal T plate and palmar
      locking plate in the treatment of unstable displaced distal radius fractures.
      METHODS: Sixty-three patients (64 radii) with distal radius fractures were
      treated with dorsal T plate (n=41) or palmar locking plate (n=23). The mean age
      was 46+/-14 years (range 21 to 82 years) in the dorsal and 47+/-14 years (range
      18 to 69 years) in the palmar plate groups. The fractures were classified
      according to the AO/ASIF system. Objective and subjective functional assessments
      were made using the Gartland-Werley and Quick-DASH scales, respectively. The mean
      follow-up was 78+/-19 months (range 12 to 101 months) and 18+/-5 months (range 12
      to 28 months) with dorsal and palmar plating, respectively. RESULTS: The mean
      Gartland-Werley and Quick-DASH scores were 2.3+/-2.1 (range 0 to 9) and 2.0+/-2.2
      (range 0 to 9) with dorsal plating, and 2.0+/-2.1 (range 0 to 6) and 1.9+/-2.7
      (range 0 to 9) with palmar plating, respectively. The two groups did not differ
      with respect to the Gartland-Werley and Quick-DASH scores (p>0.05). Time to
      return to work or daily activities was also similar (1.9+/-0.3 months vs 1.8+/
      0.4 months). However, patients treated with dorsal plating exhibited
      significantly greater values in the following parameters measured on early and
      late postoperative radiograms: loss of palmar tilt (p=0.001), radial height
      (p=0.001), radial inclination (p=0.049), and change in ulnar variance (p=0.049).
      Moreover, complications were seen in eight patients (19.5%) with dorsal plating,
      whereas no complications occurred with palmar locking plate (p=0.024).
      CONCLUSION: Although the two fixation methods do not differ with respect to
      functional results, palmar locking plating seems to provide a more rigid fixation
      resulting in significantly reduced collapse and a very low complication rate.

PMID- 19158460
TI  - [Congenital pseudarthrosis of the clavicle in two siblings].
AB  - Congenital pseudarthrosis of the clavicle is a rare disorder of unknown etiology.
      Among nearly 200 cases hitherto reported, only a few cases have familial
      coexistence, and none are first-degree relatives. A nine-year old girl had
      complaints of weakness in the right arm and swelling in the right shoulder. On
      physical examination, a mass-like lesion in the right clavicle, abnormal
      clavicular movement, and asymmetric shoulders were noted. The range of motion of
      the shoulder was in normal range on both sides. A plain radiogram showed a defect
      in the diaphysis of the right clavicle and computed tomography showed
      discontinuity of the right clavicle. Similar clinical and radiologic findings
      were also detected in her younger sister who was three years old. None had a
      history of trauma, difficult delivery, or natal complication, any abnormal
      findings related to the musculoskeletal system, any abnormality in routine
      laboratory test results and genetic analysis. The diagnosis was made as
      congenital pseudarthrosis of the clavicle in both siblings. Since they had normal
      range of joint movements without pain, they were scheduled for clinical follow
      up. To our knowledge, these two siblings are the first to be reported in the
      literature for having congenital pseudarthrosis of the clavicle.

PMID- 19158461
TI  - [A case of ancient schwannoma of the great toe].
AB  - Ancient schwannoma (degenerated neurilemmoma) is a rare form of schwannoma
      characterized by calcification and cystic degeneration. A 42-year-old male
      patient presented with a mass in the base of the left great toe, which had
      existed for eight years and undergone significant enlargement for the past six
      months. On physical examination, there was a mass, 3x2x2 cm in size, in the
      lateral aspect and base of the left great toe. Radiographic appearance of the
      feet was normal. The mass was removed by blunt dissection. No postoperative
      problems were seen. The histopathological diagnosis of the specimen was made as
      ancient schwannoma.

PMID- 19158463
TI  - [Notice of plagiarism].

PMID- 19158464
TI  - [Gastric varices treated with balloon-occluded retrograde transvenous
      obliteration (BRTO)].

PMID- 19158465
TI  - [The assessment of toxic liver injury].
AB  - Liver injury due to prescription and nonprescription medications is a growing
      medical, scientific and public health problem. Drug-induced liver injury (DILI)
      is the single most common reason for regulatory actions, including failure of
      approval, removal from the marketplace and restriction of prescription.
      Worldwide, the estimated annual incidence rate of DILI is 13.9-24.0 per 100,000
      inhabitants. At the same time, there is increasing concern about the potential
      risk for hepatotoxicity from complementary and alternative medicines (CAM)
      including herbal products because they are unregulated and not standardized with
      regard to their contents. Determining hepatotoxicity remains a major challenge in
      clinical practice due to a lack of reliable markers. The RUCAM/CIOMS scale have
      been proposed to establish a causal relationship between offending drug and liver
      injury. The efforts of Drug-Induced Liver Injury Network (DILIN, USA) directed
      toward the development of an abridged instrument in evaluating suspected drug
      induced hepatotoxicity were presented at the National Institute of Health (NIH)
      Workshop, titled Drug-induced liver injury: Standardization of nomenclature and
      causality assessment, December, 2008. The main contents of the presentations and
      discussions at the NIH workshop are introduced in this article. This fine-tuned
      operations of RUCAM/CIOMS scale would enable a more confident assessment of
      causality and facilitate the collection of bona fide cases of drug-induced
      hepatotoxicity in Korea. Several demanding tasks for the near future in Korea are
      also proposed at the end.

PMID- 19158466
TI  - [Concurrent chemoradiotherapy compared with concurrent chemoradiotherapy with
      surgery in locally advanced resectable esophageal cancer].
AB  - BACKGROUND/AIMS: This study was designed to compare the survival rates between
      patients with localized esophageal cancer who were treated with concurrent
      chemoradiation therapy without surgery and patients who were treated with
      concurrent chemoradiation therapy including surgery. METHODS: Eighty-eight
      patients from January 1997 to December 2005 with locally advanced resectable
      esophageal cancer were selected and retrospectively analyzed. Survival period was
      defined as the time to death from the date of diagnosis or mid-monitor period of
      December 2005. Sixty-one patients were treated with chemoradiation therapy alone
      while twenty-seven patients were treated with chemoradiation therapy in addition
      to surgery as for curative intention. As for radiation therapy, 5,000-5,500 cGY
      was used. 5-Fluouracil and cisplatin were used for chemotherapy. The primary end
      point was overall survival time. The secondary end point was overall progression
      free survival time. RESULTS: There was no significant difference in tissue type,
      location and clinical staging, but the median age was significantly younger in
      the group treated with surgery (63.4 years) than the group treated without
      surgery (68.8 years). Median period analyzed was 17.3 months. Five year survival
      rate for the group with chemoradiation alone was 7.4% and 4% for the group with
      surgery. The median survival rate was 11+/-3 months for the group with
      chemoradiation alone and 10+/-6 months for the group with surgery, in which there
      was no statistical difference (p=0.697). CONCLUSIONS: There was no significant
      increase in survival rate in patients who were treated by chemoradiation with
      surgery compared with chemoradiation alone. Further analysis in terms of
      prospective study is needed.

PMID- 19158467
TI  - [The clinical usefulness of focally enhanced gastritis in Korean patients with
      Crohn's disease].
AB  - BACKGROUND/AIMS: Focally enhanced gastritis (FEG) has been suggested as a
      specific diagnostic marker for patients with Crohn's disease (CD). However, the
      usefulness of FEG for distinguishing CD from ulcerative colitis (UC) is uncertain
      and the incidence or prevalence of FEG for inflammatory bowel disease (IBD)
      patients in Korea has not been defined yet. In this study, we investigated the
      frequency of FEG and other gastric histological abnormalities in Korean patients
      with CD and UC. METHODS: We evaluated 37 patients with known CD, 43 patients with
      UC and 41 non-IBD control group; all underwent upper gastrointestinal endoscopy
      followed by biopsy from the antrum and the body. The pathology of the gastric
      biopsy specimens and the presence of Helicobacter pylori (H. pylori) were
      evaluated. FEG was characterized by a focal perifoveolar or periglandular
      inflammatory cell infiltrates. RESULTS: H. pylori positive gastritis was found in
      10 of 37 (27.0%) of CD patients, in 16 of 43 (37.2%) of UC patients, and in 22 of
      41 (53.7%) of non-IBD control group (p=0.054). In H. pylori-negative patients,
      FEG was found in 8 of 27 patients (29.6%) of CD patients, 6 of 27 (22.2%)
      patients with UC, and 2 of 9 (10.5%) of non-IBD control group (p=0.324).
      CONCLUSIONS: In H. pylori-negative patients, there was no statistically
      significant difference in the occurrence of FEG among CD, UC and control groups
      in Korea.

PMID- 19158468
TI  - [Clinical efficacy of nonsurgical treatment of Crohn's disease-related
      intraabdominal abscess].
AB  - BACKGROUND/AIMS: This study was conducted to compare the clinical efficacy
      between surgical and nonsurgical treatments for patients with Crohn's disease
      related intraabdominal abscess. METHODS: A retrospective review of medical
      records was performed for patients admitted to a single institution due to
      Crohn's disease-related intraabdominal abscess from February, 1996 to February,
      2008. Clinical outcomes were compared between surgical and nonsurgical groups in
      terms of treatment responses and recurrences. RESULTS: A total of 47 episodes of
      intraabdominal abscesses in 43 patients (12.7%) were identified from 339 patients
      with Crohn's disease. Of these, initially, 18 cases (38.3%) underwent surgical
      treatment and 29 (61.7%) were treated medically (antibiotic treatments with or
      without percutaneous drainage). The overall treatment response rates of surgical
      and nonsurgical group were 100% versus 89.7% (p=0.11) and recurrence rates were
      27.8% versus 30.8% (p=1.00). Three patients in nonsurgical group (10.3%) showed
      no response to therapy and ultimately received surgical drainages. The median
      length of hospitalization in nonsurgical group was shorter than in surgical group
      (12 and 29.5 days, respectively. p=0.02). CONCLUSIONS: Nonsurgical treatment
      might be as effective as surgical treatment for the treatment of Crohn's disease
      related intraabdominal abscess, especially considering shorter hospital stay.

PMID- 19158469
TI  - [The effect of post-biopsy scar on the submucosal elevation for endoscopic
      resection of rectal carcinoids].
AB  - BACKGROUND/AIMS: While endoscopic resection could be considered as the best
      choice for the treatment of small rectal carcinoid, the colonoscopic biopsies
      performed at the time of detection may lead to scar and ulcer formation and cause
      unpredicted difficulty in the endoscopic resection. This study was evaluated to
      analyze the relationship between the post-biopsy scar and the limitation of
      submucosal elevation for the endoscopic resection of rectal carcinoids. METHODS:
      Twenty two cases of rectal carcinoid which received prior biopsies before the
      endoscopic resection were retrospectively compared with 20 non-biopsied cases.
      All two groups were treated by endoscopic resection from January 2000 to December
      2007. There was no difference in the clinical characteristics and endoscopic
      findings such as size and location between the two groups. RESULTS: The limited
      submucosal elevation was experienced in 17 cases (77%) in the biopsy group,
      significantly more frequent than 9 cases (45%) in the non-biopsy group (p=0.03).
      The colonoscopic findings which contribute to difficult submucosal elevation were
      the depressive scar formation after biopsy, the size less than 5 mm in the biopsy
      group, active ulcer formation after biopsy. Regarding the resection method,
      endoscopic submucosal dissection was frequently adopted (23% vs. 5%) in the
      biopsy group. The frequency of endoscopic piecemeal resection in biopsy group was
      higher than non-biopsy group (23% vs 10%), and all cases were subsequently
      resected by other endoscopic methods. CONCLUSIONS: The post-biopsy scar can
      interfere with successful submucosal elevation for endoscopic resection of rectal
      carcinoids. The number of forceps biopsy should be minimized in the diagnostic
      colonoscopy when endoscopic resection is planned rectal carcinoids.

PMID- 19158470
TI  - [A case of gastric candidiasis presented as subepithelial mass in an
      immunocompromised host].
AB  - Hepatosplenic candidiasis is also called chronic disseminated candidiasis and
      usually seen in patients with hematologic malignancies who have just recovered
      from an episode of neutropenia. Gastric candidiasis most commonly present as a
      mucosal lesion such as an ulcer or erosions, but other gastric lesion is very
      rare. We experienced a case of gastric candidiasis which presented as gastric
      subepithelial mass in a 60-year old woman who had undergone the 2nd consolidation
      chemotherapy due to acute myeloid leukemia. The pathologic diagnosis was
      confirmed by fine needle aspiration of the gastric subepithelial mass under the
      guidance of endoscopic ultrasonography.

PMID- 19158471
TI  - [A case of pulmonary thromboembolism in active ulcerative colitis].
AB  - Inflammatory bowel disease often involves extra-intestinal organs. Cerebral
      thrombosis, portal vein thrombosis and pulmonary thrombosis have been reported.
      Deep vein thrombosis and pulmonary thromboembolism are significant causes of
      mortality in patients with inflammatory bowel disease. A 48-year-old woman was
      diagnosed as inflammatory bowel disease on colonoscopy and histology. We used
      hydrocortisone and mesalazine for the treatment of disease. Nineteen days later,
      she complained of abrupt dyspnea. Pulmonary CT angiography revealed a
      thromboembolism in right pulmonary arteries. After the treatment of heparin
      therapy, follow-up pulmonary CT angiography showed significant improvement of
      previously thrombosed pulmonary arteries.

PMID- 19158472
TI  - [A case of pseudomembranous colitis associated with rifampicin therapy in a
      patient with rectal cancer and gastrointestinal tuberculosis].
AB  - Pseudomembranous colitis (PMC) is known to be associated with the administration
      of antibiotics which alter normal gastrointestinal flora and allow overgrowth of
      Clostridium difficile. Most cases of rifampicin-induced PMC are seen in patients
      with pulmonary tuberculosis, but not with gastrointestinal tuberculosis. We
      report a case of PMC associated with rifampicin therapy in a patient with
      gastrointestinal tuberculosis. A 65-year-old female patient with rectal cancer
      and gastrointestinal tuberculosis was admitted due to abdominal pain and
      diarrhea. She was treated with anti-tuberculosis agents containing rifampicin. On
      colonoscopic examination, mucoid exudates and yellowish plaque lesions were
      observed. Anti-tuberculosis agents were stopped, and the patient was treated with
      metronidazole. Symptoms were relieved and did not recur when all the anti
      tuberculosis agents except rifampicin were started again. When a patient
      complains of abdominal pain or diarrhea while taking rifampicin, the physician
      should consider the possibility of rifampicin-associated PMC.

PMID- 19158473
TI  - [A case of acute pancreatitis and splenic infarction associated with
      antiphospholipid syndrome].
AB  - There are various causes of splenic infarction. Antiphospholipid antibody is
      associated with numerous thromboembolic phenomena. We report a case of young male
      who presented with acute abdominal pain and was diagnosed as a case of splenic
      infarction and acute pancreatitis with antiphospholipid syndrome. He was positive
      for anticardiolipin antibody, showed splenic infarction on abdominal CT scan. The
      patient's clinical, laboratory and imaging finding were consistent with splenic
      infarction and acute pancreatitis associated with antiphospholipid syndrome.

PMID- 19158474
TI  - [Treatment for intraabdominal abscess in Crohn's disease].

PMID- 19158476
TI  - Survivin as a universal tumor antigen for novel cancer immunotherapy: functions
      of a killer clone.

PMID- 19158477
TI  - Molecular identity of a pan cancer marker, CA215.
AB  - The molecular nature of cancer-associated antigen, CA215 which reacts with RP215
      monoclonal antibody and its unique epitope(s)was characterized. RP215 was
      initially selected and produced from one of 3,000 hybridomas which were generated
      from mice immunized with the cell extract of OC-3-VGH ovarian cancer cells. This
      cancer-associated antigen from various sources including cancer cell extract,
      shed culture medium and affinity-purified forms was analyzed by MALDI-TOF MS
      (Matrix Adsorption Laser Desorption Ionization-Time of Flight Mass Spectrometry),
      Western blot, carbohydrate profiling as well as enzyme immunoassays. The results
      of this study showed that CA215 is homologous to the heavy chains of human
      immunoglobulins with molecular sizes ranging from 50 to 70 KDa, when probed with
      RP215 or anti-human immunoglobulin G, A or M. Treatments of cancer cells with
      NaIO(4) drastically reduce RP215 binding to the carbohydrate-associated
      epitope(s) of CA215 located on the variable domain of the human immunoglobulin
      heavy chains. Further studies indicated that CA215 is predominantly expressed by
      cancer cells in both secreted and membrane-bound monomeric forms. The
      carbohydrate-associated epitope(s) with pH-sensitive immunoactivity appear to be
      present only in cancer cell-derived immunoglobulins, but not in normal human
      immunoglobulins. Compared to normal immunoglobulin G, CA215 contains a
      significantly higher percentage of N-acetyl and N-glycoyl neuraminic acid (28%
      vs. 8%) in the O-linked glycans, but a lower content of N-acetylglucosamine (28%
      vs. 41%) in the N-linked ones. It was concluded from this study that RP215 reacts
      specifically with carbohydrate-associated epitope(s) of immunoglobulin heavy
      chains expressed by various human cancer cells.

PMID- 19158478
TI  - Insulin withdrawal-induced cell death in adult hippocampal neural stem cells as a
      model of autophagic cell death.
AB  - The term "autophagic cell death" was coined to describe a form of cell death
      associated with the massive formation of autophagic vacuoles without signs of
      apoptosis. However, questions about the actual role of autophagy and its
      molecular basis in cell death remain to be elucidated. We recently reported that
      adult hippocampal neural stem (HCN) cells undergo autophagic cell death following
      insulin withdrawal. Insulin-deprived HCN cells exhibit morphological and
      biochemical markers of autophagy, including accumulation of Beclin 1 and the type
      II form of microtubule-associated protein 1 light chain 3 (LC3) without evidence
      of apoptosis. Suppression of autophagy by knockdown of Atg7 reduces cell death,
      whereas promotion of autophagy with rapamycin augments cell death in insulin
      deficient HCN cells. These data reveal a causative role of autophagy in insulin
      withdrawal-induced HCN cell death. HCN cells have intact apoptotic capability
      despite the lack of apoptosis following insulin withdrawal. Our study
      demonstrates that autophagy is the default cell death mechanism in insulin
      deficient HCN cells, and provides a genuine model of autophagic cell death in
      apoptosis-intact cells. Novel insight into molecular mechanisms of this
      underappreciated form of programmed cell death should facilitate the development
      of therapeutic methods to cope with human diseases caused by dysregulated cell
      death.

PMID- 19158479
TI  - Low risk HPV-E6 traps p53 in the cytoplasm and induces p53-dependent apoptosis.

PMID- 19158480
TI  - Troglitazone-mediated sensitization to TRAIL-induced apoptosis is regulated by
      proteasome-dependent degradation of FLIP and ERK1/2-dependent phosphorylation of
      BAD.
AB  - Resistance to apoptosis is one reason for the poor response of malignant brain
      tumors to therapy. The PPARgamma-modulating drug Troglitazone downregulates the
      anti-apoptotic FLIP protein and sensitizes glioblastoma cells to apoptosis
      induced by the death ligand TRAIL. To investigate the molecular basis of an
      experimental combination therapy for malignant gliomas with TRAIL and
      Troglitazone, we investigated the Troglitazone-induced signaling cascades and the
      expression of TRAIL receptors and FLIP in malignant gliomas. Troglitazone
      downregulated the FLIP protein through accelerated ubiquitin/proteasome-dependent
      degradation, which might be mediated by a Troglitazone-induced increase in
      reactive oxygen species. Moreover, Troglitazone induced the phosphorylation of
      the MAP kinase ERK1/2 as well as of the BAD protein. Inhibition of either
      PPARgamma or MEK1/2 blocked the Troglitazone-mediated phosphorylation of BAD and
      further increased the synergistic induction of glioma cell death by TRAIL and
      Troglitazone. Immunohistochemical analysis demonstrated that FLIP and TRAIL-R2
      were significantly higher expressed in anaplastic (WHO grade III) than in diffuse
      (WHO grade II) gliomas. High FLIP and low TRAIL-R2 expression levels were
      associated with a poor prognosis of patients. Our findings warrant a further pre
      clinical evaluation of an experimental anti-glioma therapy with TRAIL and
      Troglitazone, potentially in conjunction with a MAP kinase inhibitor.

PMID- 19158481
TI  - FLIPing the apoptosis switch on in brain tumors using Troglitazone and TRAIL.

PMID- 19158482
TI  - The current STATe of biomarkers to predict the response to anti-angiogenic
      therapies.

PMID- 19158483
TI  - Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms
      for repair and chemoresistance.
AB  - A major burden in the treatment of ovarian cancer is the high percentage of
      recurrence and chemoresistance. Cancer stem cells (CSCs) provide a reservoir of
      cells that can self-renew, can maintain the tumor by generating differentiated
      cells [non-stem cells (non-CSCs)] which make up the bulk of the tumor and may be
      the primary source of recurrence. We describe the characterization of human
      ovarian cancer stem cells (OCSCs). These cells have a distinctive genetic profile
      that confers them with the capacity to recapitulate the original tumor,
      proliferate with chemotherapy, and promote recurrence. CSC identified in EOC
      cells isolated form ascites and solid tumors are characterized by: CD44+, MyD88+,
      constitutive NFkappaB activity and cytokine and chemokine production, high
      capacity for repair, chemoresistance to conventional chemotherapies, resistance
      to TNFalpha-mediated apoptosis, capacity to form spheroids in suspension, and the
      ability to recapitulate in vivo the original tumor. Chemotherapy eliminates the
      bulk of the tumor but it leaves a core of cancer cells with high capacity for
      repair and renewal. The molecular properties identified in these cells may
      explain some of the unique characteristics of CSCs that control self-renewal and
      drive metastasis. The identification and cloning of human OCSCs can aid in the
      development of better therapeutic approaches for ovarian cancer patients.

PMID- 19158484
TI  - Inhibition of p27Kip1 gene transcription by mitogens.
AB  - How mitogens reduce the abundance of the cell cycle inhibitor p27(Kip1) is an
      important question, and regulation of p27(Kip1) translation and turnover has been
      described. Here we show that platelet-derived growth factor (PDGF) reduces the
      activity of the p27(Kip1) promoter and the abundance of the p27(Kip1) transcript
      in density-arrested mouse fibroblasts. Inhibition of p27(Kip1) gene expression by
      PDGF required protein synthesis and histone deacetylase activity but not Akt or
      ERK activity. PDGF increased the expression of c-Myc in the absence but not
      presence of a histone deacetylase inhibitor, and c-Myc inhibited p27(Kip1)
      promoter activity when ectopically expressed in fibroblasts. c-Myc targeted the
      same region of the p27(Kip1) promoter as did PDGF (deletion analysis) and
      interacted with this region in vivo (chromatin immunoprecipitation assay).
      Collectively, these findings suggest that c-Myc mediates the inhibitory effects
      of PDGF on the p27(Kip1) promoter. We also demonstrate reductions in p27(Kip1)
      mRNA abundance in primary splenocytes exposed to concanavalin A and in T cells
      exposed to interleukin-2 (IL-2). In contrast to PDGF in fibroblasts, IL-2
      required Akt activity for maximal reductions in p27(Kip1) promoter activity and
      mRNA abundance in T cells. Thus, mitogens repress p27(Kip1) gene transcription in
      multiple systems and by multiple mechanisms.

PMID- 19158485
TI  - Phosphorylation of survivin at threonine 34 inhibits its mitotic function and
      enhances its cytoprotective activity.
AB  - Survivin is an essential chromosomal passenger protein required for mitotic
      progression. It is also an inhibitor of apoptosis and can prevent caspase
      mediated cell death. In addition, survivin levels are elevated in cancer cells
      where its presence correlates with increased resistance to chemo- and radio
      therapy, which makes it an attractive target for novel anti-cancer strategies.
      Interestingly, survivin is phosphorylated by the mitotic kinase, cdk1, and a
      nonphosphorylatable form, survivin(T34A), cannot inhibit apoptosis. Here we
      rigorously test the ability of survivin(T34A) and its corresponding
      phosphomimetic, survivin(T34E), to promote cell viability through survivin's dual
      roles. The effects of these mutations are diametrically opposed: survivin(T34A)
      accelerates cell proliferation and promotes apoptosis, whereas survivin(T34E)
      retards growth and promotes survival. Thus the phosphorylation status of survivin
      at T34 is pivotal to a cell's decision to live or die.

PMID- 19158486
TI  - Androgenic regulation of hedgehog signaling pathway components in prostate cancer
      cells.
AB  - Hedgehog signaling is thought to play a role in several human cancers including
      prostate cancer. Although prostate cancer cells express many of the gene products
      involved in hedgehog signaling, these cells are refractory to the canonical
      signaling effects of exogenous hedgehog ligands or to activated Smoothened, the
      hedgehog-regulated mediator of Gli transcriptional activation. Here, we show that
      the expression of hedgehog ligands and some hedgehog target genes are regulated
      by androgen in the human prostate cancer cell line, LNCaP and its more metastatic
      variants (C4-2 and C4-2B). Androgen (R1881) strongly suppressed the expression of
      hedgehog ligands in these cells and their prolonged maintenance in androgen
      deficient medium upregulated Sonic and Indian hedgehog mRNA and protein levels by
      up to 30,000-fold. Hedgehogs were released into the conditioned medium of
      androgen-deprived LNCaP cells and this medium was able to increase hedgehog
      target gene expression in hedgehog-responsive mouse fibroblasts (MC3T3-E1).
      Moreover, this activity was accompanied by increased expression of Gli target
      genes, Patched 1 and Gli2, in LNCaP that could be suppressed by cyclopamine,
      indicating that chronic androgen-deprivation also re-awakens the autocrine
      responsiveness of the cancer cells to hedgehog. In contrast to the suppressive
      effects of R1881 on hedgehog ligand and Gli2 expression, we found that Gli1
      expression in LNCaP cells was induced by R1881. Given the ability of androgen to
      modulate the expression and release of hedgehog ligands and the activity of the
      autocrine hedgehog signaling pathway in these prostate cancer cells, our results
      imply that chronic androgen deprivation therapy (ADT) for prostate cancer might
      create a hedgehog signaling environment in the region of the tumor that could
      ultimately impact on the long term effectiveness of this treatment. This
      consideration supports the idea of clinically testing hedgehog-blocking drugs in
      conjunction with ADT in patients with advanced prostate cancer.

PMID- 19158488
TI  - All eukaryotes: before turning off G1-S transcription, please check your DNA.
AB  - The DNA replication and DNA damage checkpoints are required for the efficient
      response to genotoxic stress, which is critical for genome stability and cell
      survival. The DNA replication and damage checkpoints delay progression into
      mitosis, and at the same time induce the transcription of genes that promote
      repair of cellular lesions including stabilization of stalled replication forks
      and induction of DNA repair functions. The elucidation of the mechanism by which
      the DNA replication checkpoint activates transcription of G1/S genes is provided
      by our recent study reported in the August issue of Proceedings of the National
      Academy of Sciences. We show that, in response to stimulation of the DNA
      replication checkpoint, activation of G1-S transcription is established by
      inactivation, via phosphorylation by the checkpoint protein kinases, of the MBF
      associated transcriptional corepressor Nrm1. This regulation is critical for the
      survival of cells responding to genotoxic stress. This provides a simple but
      elegant mechanism by which checkpoint activation can override the regular
      periodic transcriptional program by directly regulating a cell cycle dependent
      transcriptional repressor. We discuss the likely conservation of this regulatory
      pathway in yeast and man.

PMID- 19158487
TI  - Nek1 regulates cell death and mitochondrial membrane permeability through
      phosphorylation of VDAC1.
AB  - The mammalian NIMA-related protein kinase 1 (Nek1) is important for keeping cells
      alive after DNA damage, but the mechanism by which injured cells die without
      functional Nek1 has not yet been demonstrated. Here we show that Nek1 regulates
      the pathway to mitochondrial cell death through phosphorylation of voltage
      dependent anion channel 1 (VDAC1) on serine 193. Nek1 associates with VDAC1 in a
      yeast two-hybrid system, as well as by GST pull-down assays and by reciprocal
      immunoprecipitation. A portion of Nek1 in cells also localizes at mitochondria.
      Ectopic expression of a kinase-dead Nek1 mutant results in cell death, which is
      immediately preceded by loss of the Nek1-dependent VDAC1-S193 phosphorylation. UV
      irradiation of Nek1-deficient cells or silencing of endogenous Nek1 expression
      similarly results in loss of the specific S193 phosphorylation before cells die.
      Nek1-deficient cells are characterized by exaggerated mitochondrial membrane
      permeability (MMP) and accelerated cell death. Ectopic expression of a VDAC1
      Ser193Ala mutant, which cannot be phosphorylated by Nek1, also results in cell
      death. A VDAC1-Ser193Glu mutant, designed to mimic constitutive phosphorylation
      by Nek1, rescues exaggerated MMP and keeps cells alive after DNA damaging injury,
      but only transiently. The direct interaction between Nek1 and VDAC1 provides a
      mechanism to explain how Nek1 prevents excessive cell death, as well as the first
      direct evidence that a specific kinase regulates VDAC1 activity.

PMID- 19158489
TI  - The ubiquitin-selective chaperone CDC-48/p97, a new player in DNA replication.
AB  - Efficient duplication of the genome and its equal distribution into both daughter
      cells is an essential process for all dividing organisms. To ensure that DNA
      replication occurs only once during the S phase of the cell cycle, initiation of
      replication is tightly controlled. Initiation factors are responsible for the
      recruitment of the replisome, the large molecular machine carrying out DNA
      synthesis, to origins of replication and license them to start DNA duplication.
      Remarkably, most of the currently known initiators have been classified as
      members of the family of AAA(+) ATPases. In our recent study we identified an
      additional AAA(+) ATPase, CDC-48, to be essential for proper DNA replication in
      Caenorhabditis elegans. Here, we speculate on the function of CDC-48 (also known
      as Cdc48p in yeast and p97 in vertebrates) during DNA replication initiation,
      addressing its ubiquitin-selective chaperone activity.

PMID- 19158490
TI  - Tumor endothelial cells have features of adult stem cells.
AB  - We recently reported that prostate tumor-specific endothelial cells had features
      of mesenchymal stem cells and could transdifferentiate to form cartilage and bone
      like tissues. Plasticity in the tumor vasculature may be related to well-known
      tumor blood vessel abnormalities and could underlie an intrinsic adaptive
      mechanism in tumor endothelial cells for circumventing anti-angiogenic
      strategies.

PMID- 19158491
TI  - Bck2 is a phase-independent activator of cell cycle-regulated genes in yeast.
AB  - During the cell division cycle of the yeast Saccharomyces cerevisiae, the G1-to-S
      transition depends upon the activation of two transcription factors (SBF and
      MBF), which are responsible for the cell cycle-regulated expression of more than
      200 genes. Bck2 becomes essential in the absence of Cln3, the most upstream
      activator of this transcriptional program. Here we have used a genome-wide
      approach to elucidate the targets of Bck2. Our data indicate that Bck2 activates
      a selection of cell cycle-regulated genes from all cell cycle stages. In
      contrast, Cln3 activates only G1/S phase genes. Furthermore, Bck2 activates many
      genes independently of Swi6, the common component of SBF and MBF. Comparison of
      Bck2 targets with those of other transcription factors suggests that, in addition
      to SBF and MBF, Bck2 may elicit gene expression via Ste12 and Mcm1. We propose
      that Bck2 activates its targets by a mechanism fundamentally different from that
      of Cln3, and that it may be a necessary cofactor for the full expression of a
      subset of cell cycle-regulated genes.

PMID- 19158492
TI  - The role of autophagy in pancreatic beta-cell and diabetes.
AB  - Pancreatic beta-cells play a key role in glucose homeostasis in mammals. Although
      large-scale protein synthesis and degradation occur in pancreatic beta-cells, the
      mechanism underlying dynamic protein turnover in beta-cells remains largely
      unknown. We found low-level constitutive autophagy in beta-cells of C57BL/6 mice
      fed a standard diet; however, autophagy was markedly upregulated in mice fed a
      high-fat diet. beta-cells of diabetic db/db mice contained large numbers of
      autophagosomes, compared with nondiabetic db/misty controls. The functional
      importance of autophagy was analyzed using beta-cell-specific Atg7 knockout mice.
      Autophagy-deficient mice showed degeneration of beta-cells and impaired glucose
      tolerance with reduced insulin secretion. While a high-fat diet stimulated beta
      cell autophagy in control mice, it induced a profound deterioration of glucose
      intolerance in beta-cell autophagy-deficient mutants, partly because of the lack
      of a compensatory increase in beta-cell mass. These results suggest that the
      degradation of unnecessary cellular components by autophagy is essential for
      maintenance of the architecture and function of beta-cells. Autophagy also serves
      as a crucial element of stress responses to protect beta-cells under insulin
      resistant states. Impairment of autophagic machinery could thus predispose
      individuals to type 2 diabetes.

PMID- 19158493
TI  - p21Cip1/WAF1 mediates cyclin B1 degradation in response to DNA damage.
AB  - p21(Cip1/WAF1) is the principle mediator of cell cycle arrest in response to DNA
      damage. p21 primarily mediates G(1) cell cycle arrest by inactivating G(1)
      associated cyclin A- and cyclin E-containing cyclin/cdk complexes. In the present
      study we investigate the role of p21 in DNA damage-induced G(2) cell cycle
      arrest, particularly with respect to the G(2)-associated cyclin, cyclin B1. We
      demonstrate that cells lacking p21 or deficient in their ability to upregulate
      p21 are unable to mediate the downregulation of cyclin B1 in response to DNA
      damage as compared to wild-type cells. Decreased levels of cyclin B1 in response
      to DNA damage seen in wild-type cells is due to p21-mediated degradation of
      cyclin B1 as this can be inhibited by a proteasomal inhibitor. Cell cycle
      analysis reveals that p21-null cells are unable sustain G(2) cell cycle arrest
      and accumulate at greater than 4N DNA content. These results indicate that p21
      mediated degradation of cyclin B1 in response to DNA damage is necessary for the
      maintenance of G(2) cell cycle arrest.

PMID- 19158494
TI  - Participation of autophagy in the initiation of graft dysfunction after rat liver
      transplantation.
AB  - Better ways to prevent the cold ischemia-warm reperfusion (CI/WR) injury
      associated with liver transplantation are needed, and many investigations have
      focused on the molecular mechanisms of this injury. However, the mechanisms
      reported to date are controversial and no improvement in therapy has resulted.
      Here, using prolonged CI and orthotopic transplantation of rat liver grafts, we
      found that the CI/WR injury was closely associated with autophagy. By 15 minutes
      after the start of WR, small masses of hepatocytes that possessed abundant
      autophagosomes and autolysosomes frequently dissociated from the hepatic cords
      and obstructed the sinusoid, causing massive necrosis of hepatocytes within 2
      hours. The cell masses included TUNEL-positive nuclei without caspase-3 and -7
      activation. Autophagy suppression with the phosphatidylinositol 3-kinase (PI3K)
      inhibitors, wortmannin or LY294002, reduced both liver damage and the mortality
      rate of recipient rats. To elucidate the downstream mechanisms of this autophagic
      pathway, liver grafts were treated with aspartic and cysteine proteinase
      inhibitors, pepstatin and leupeptin. This treatment also significantly improved
      the survival rate of recipient rats. These data suggest that autophagy-associated
      hepatocyte death triggers liver graft dysfunction. The protective effects of
      suppressing autophagy may suggest new ways to prevent CI/WR injury of the liver.

PMID- 19158495
TI  - TMAP/CKAP2 is essential for proper chromosome segregation.
AB  - Tumor-associated microtubule-associated protein (TMAP), also known as
      cytoskeleton associated protein 2 (CKAP2), is a novel mitotic spindle-associated
      protein which is frequently up-regulated in various malignances. However, its
      cellular functions remain unknown. Previous reports suggested that the cellular
      functions of TMAP/CKAP2 pertain to regulation of the dynamics and assembly of the
      mitotic spindle. To investigate its role in mitosis, we studied the effects of
      siRNA-mediated depletion of TMAP/CKAP2 in cultured mammalian cells. Unexpectedly,
      TMAP/CKAP2 knockdown did not result in significant alterations of the spindle
      apparatus. However, TMAP/CKAP2-depleted cells often exhibited abnormal nuclear
      morphologies, which were accompanied by abnormal organization of the nuclear
      lamina, and chromatin bridge formation between two daughter cell nuclei. Time
      lapse video microscopy revealed that the changes in nuclear morphology and
      chromatin bridge formations observed in TMAP/CKAP2-depleted cells are the result
      of defects in chromosome segregation. Consistent with this, the spindle
      checkpoint activity was significantly reduced in TMAP/CKAP2-depleted cells.
      Moreover, chromosome missegregation induced by depletion of TMAP/CKAP2 ultimately
      resulted in reduced cell viability and increased chromosomal instability. Our
      present findings demonstrate that TMAP/CKAP2 is essential for proper chromosome
      segregation and for maintaining genomic stability.

PMID- 19158496
TI  - The role of autophagy in spinal cord injury.
AB  - Previous studies have indicated that autophagy has an important function, not
      only in many neurodegenerative diseases, but also in traumatic and ischemic brain
      injury. However, no study has previously shown the contribution of autophagy to
      neural tissue damage after spinal cord injury. We recently investigated the
      alterations in Beclin 1 expression and the involvement of autophagy and
      autophagic cell death after spinal cord injury using a spinal cord hemisection
      model in mice. The results showed that the expression of Beclin 1 dramatically
      increased in the damaged neural tissue and induced autophagic cell death after a
      spinal cord injury. These observations suggested that the increased expression of
      Beclin 1 activates autophagy, while mediating a novel cell death mechanism at the
      lesion site in response to spinal cord injury. Here we discuss several unsolved
      issues and review the evidence in related articles regarding the role of
      autophagy and its contribution to the mechanism of cell death in spinal cord
      injury.

PMID- 19158497
TI  - The translation initiation factor DAP5 is a regulator of cell survival during
      mitosis.
AB  - Initiation of protein translation is tightly regulated by various physiological
      signals and involves cap-dependent and independent mechanisms. DAP5 protein is an
      eIF4G family member previously implicated in mediating cap-independent IRES
      driven translation in response to various cellular stresses. Unexpectedly, we
      have recently found that DAP5 is also essential for continuous cell survival in
      non-stressed cells. We reported in this respect that the knock down of endogenous
      DAP5 by RNA-interference induces M-phase specific caspase-dependent cell death.
      Bcl-2 and CDK1 were identified as DAP5 mRNA targets, the translation of which was
      selectively reduced in the DAP5 knock down cells. They each possess a functional
      IRES element in their 5'UTR. Here we review the major results of this study and
      present new data on the link of DAP5 to additional Bcl-2 family members. In
      addition we discuss other possible cellular phenotypes resulting from the knock
      down of DAP5 in these cells.

PMID- 19158498
TI  - Gene fusions and RNA trans-splicing in normal and neoplastic human cells.
AB  - Chimeric gene products, most often resulting from chromosome translocations, have
      been considered unique features of cancer, or at least of cells at high risk for
      becoming cancerous. Chimeric JAZF1-JJAZ1 mRNA transcribed from DNA spanning the
      site of recombination in the (7;17)(p15;q21) chromosomal translocation found in
      half of endometrial stromal sarcomas and most cases of benign stromal nodules is
      one such example. The recent finding that chimeric JAZF1-JJAZ1 mRNA can also be
      detected in normal endometrial stromal cells suggests that chimeric gene products
      are not limited to cancer or pre-cancerous cells. The JAZF1-JJAZ1 mRNA and the
      protein encoded by it appear to be identical to that synthesized from the gene
      fusion in neoplastic cells. In cultured cells, the chimeric protein has anti
      apoptotic properties and is pro-proliferative when unrearranged JJAZ1 alleles are
      silenced, as they are in endometrial stromal sarcomas but not in the stromal
      nodules. These observations are consistent with the conclusion that chromosomal
      rearrangements and gene fusions in neoplastic cells may represent mechanisms for
      the deregulated expression of chimeric gene products that are generated at
      specific stages in cell development and have physiologic functions in normal
      cells. Furthermore, it may be possible that other means for abnormal production
      of chimeric gene products, such as hyperactive transsplicing of RNA, may be
      another mechanism underlying the neoplastic properties of tumor cells.

PMID- 19158499
TI  - Cdk5 acts as a mediator of neuronal cell cycle re-entry triggered by amyloid-beta
      and prion peptides.
AB  - Cyclin-dependent kinase 5 (Cdk5) is a serine-threonine kinase important for
      different cellular processes. Involved in tau protein hyperphosphorylation and
      apoptotic neuronal death, two main neuropathological markers of Alzheimer's
      disease (AD) and Prion-related encephalopathies (PRE), Cdk5 also participates in
      cell cycle regulation. However, the precise relationship between cell cycle
      reactivation and Cdk5 dysregulation in AD and PRE remains unclear. To determine
      Cdk5 involvement in the triggering of an abortive cell cycle by amyloid-beta
      (Abeta) and prion (PrP) peptides, associated with AD and PRE pathogenesis, we
      examined the levels/activation of several cell cycle-associated proteins in
      cultured cortical neurons treated with Abeta1-40 and PrP106-126 peptides. Peptide
      treatments significantly increased Cdk4, phospho-retinoblastoma and proliferating
      cell nuclear antigen (PCNA) levels, whereas phospho-histone H3 remained
      invariable, suggesting cell cycle arrest before the M phase. Moreover, Abeta1-40
      and PrP106-126 largely augmented the number of PCNA-immunoreactive cells with
      fragmented nuclei. The Cdk5 inhibitor roscovitine and the calpain inhibitor
      MDL28170 prevented the alterations in cell cycle markers induced by both
      peptides. The data obtained suggest that Abetaand PrP peptides induced neuronal
      cell cycle re-entry through a mechanism involving Cdk5 dysregulation. Therefore,
      cell cycle reactivation mediated by Cdk5 can underlie the neurodegenerative
      processes that occur in AD and PRE.

PMID- 19158500
TI  - Biological and biochemical characterization of L-type-like bovine spongiform
      encephalopathy (BSE) detected in Japanese black beef cattle.
AB  - A case of L-type-like atypical bovine spongiform encephalopathy was detected in
      14-year-old Japanese black beef cattle (BSE/JP24). To clarify the biological and
      biochemical properties of the prion in BSE/JP24, we performed a transmission
      study with wild-type mice and bovinized transgenic mice (TgBoPrP). The BSE/JP24
      prion was transmitted to TgBoPrP mice with the incubation period of 199.7 +/- 3.4
      days, which was shorter than that of classical BSE (C-BSE) (223.5 +/- 13.5 days).
      Further, C-BSE was transmitted to wild-type mice with the incubation period of
      about 409 days, whereas BSE/JP24 prion inoculated mice showed no clinical signs
      up to 649 days. Severe vacuolation and a widespread and uniform distribution of
      PrP(Sc) were pathologically observed in the brain of BSE/JP24 prion affected
      TgBoPrP mice. The molecular weight and glycoform ratio of PrP(Sc) in BSE/JP24
      were different from those in C-BSE, and PrP(Sc) in BSE/JP24 exhibited weaker
      proteinase K resistance than that in C-BSE. These findings revealed that the
      BSE/JP24 prion has distinct biological and biochemical properties reported for
      that of C-BSE. Interestingly, a shorter incubation period was observed at the
      subsequent passage of the BSE/JP24 prion to TgBoPrP mice (152.2 +/- 3.1 days).
      This result implies that BSE/JP24 prion has newly emerged and showed the
      possibility that L-type BSE prion might be classified into multiple strains.

PMID- 19158505
TI  - Amyloid fibrils: abnormal protein assembly.
AB  - Amyloid refers to the abnormal fibrous, extracellular, proteinaceous deposits
      found in organs and tissues. Amyloid is insoluble and is structurally dominated
      by beta-sheet structure. Unlike other fibrous proteins it does not commonly have
      a structural, supportive or motility role but is associated with the pathology
      seen in a range of diseases known as the amyloidoses. These diseases include
      Alzheimer's, the spongiform encephalopathies and type II diabetes, all of which
      are progressive disorders with associated high morbidity and mortality. Not
      surprisingly, research into the physicochemical properties of amyloid and its
      formation is currently intensely pursued. In this chapter we will highlight the
      key scientific findings and discuss how the stability of amyloid fibrils impacts
      on bionanotechnology.

PMID- 19158506
TI  - Antagonistic roles of the N-terminal domain of prion protein to doppel.
AB  - Prion protein (PrP)-like molecule, doppel (Dpl), is neurotoxic in mice, causing
      Purkinje cell degeneration. In contrast, PrP antagonizes Dpl in trans, rescuing
      mice from Purkinje cell death. We have previously shown that PrP with deletion of
      the N-terminal residues 23-88 failed to neutralize Dpl in mice, indicating that
      the N-terminal region, particularly that including residues 23-88, may have trans
      protective activity against Dpl. Interestingly, PrP with deletion elongated to
      residues 121 or 134 in the N-terminal region was shown to be similarly neurotoxic
      to Dpl, indicating that the PrP C-terminal region may have toxicity which is
      normally prevented by the N-terminal domain in cis. We recently investigated
      further roles for the N-terminal region of PrP in antagonistic interactions with
      Dpl by producing three different types of transgenic mice. These mice expressed
      PrP with deletion of residues 25-50 or 51-90, or a fusion protein of the N
      terminal region of PrP with Dpl. Here, we discuss a possible model for the
      antagonistic interaction between PrP and Dpl.

PMID- 19158507
TI  - Reversible monomer-oligomer transition in human prion protein.
AB  - The structure and the dissociation reaction of oligomers Pr(Poligo) from reduced
      human prion huPrP(C)(23-231) have been studied by (1)H-NMR and tryptophan
      fluorescence spectroscopy at varying pressure, along with circular dichroism and
      atomic force microscopy. The 1H-NMR and fluorescence spectral feature of the
      oligomer is consistent with the notion that the N-terminal residues including all
      seven Trp residues, are free and mobile, while residues 105 approximately 210,
      comprising the AGAAAAGA motif and S1-Loop-HelixA-Loop-S2-Loop-HelixC, are engaged
      in intra- and/ or inter-molecular interactions. By increasing pressure to 200
      MPa, the oligomers tend to dissociate into monomers which may be identified with
      PrP(C*), a rare metastable form of PrP(C) stabilized at high pressure (Kachel et
      al., BMC Struct Biol 6:16). The results strongly suggest that the oligomeric form
      PrP(oligo) is in dynamic equilibrium with the monomeric forms via PrP(C*), namely
      huPrP(C)[left arrow over right arrow]huPrP(C*)[left arrow over right
      arrow]huPrP(oligo).

PMID- 19158508
TI  - Fine-tuning of nuclear-catenin by Chibby and 14-3-3.
AB  - Chibby (Cby) is an evolutionarily conserved antagonist of beta-catenin, a central
      player of the canonical Wnt signaling pathway, which acts as a transcriptional
      coactivator. Cby physically interacts with the C-terminal activation domain of
      beta-catenin and blocks its transcriptional activation potential through
      competition with DNA-binding Tcf/Lef transcription factors. Our recent study
      revealed a second mechanism for Cby-mediated beta-catenin inhibition in which Cby
      cooperates with 14-3-3 adaptor proteins to facilitate nuclear export of beta
      catenin, following phosphorylation of Cby by Akt kinase. Therefore, our findings
      unravel a novel molecular mechanism regulating the dynamic nucleo-cytoplasmic
      trafficking of beta-catenin and provide new insights into the cross-talk between
      the Wnt and Akt signaling pathways. Here, we review recent literature concerning
      Cby function and discuss our current understanding of the relationship between
      Wnt and Akt signaling.

PMID- 19158509
TI  - Nitrosative stress suppresses checkpoint activation after DNA synthesis
      inhibition.
AB  - DNA synthesis is promoted by the dephosphorylation and activation of cyclin
      dependent kinase 2 (Cdk2) complexes by Cdc25A. Nitrosative stress suppresses Cdk2
      dephosphorylation by Cdc25A in vitro and inhibits Cdc25A protein translation in
      cells, but the effects on S-phase progression remain unexamined. Herein we report
      that nitrosative stress catalyzed by inducible nitric oxide (*NO) synthase (iNOS)
      or the chemical nitrosant S-nitrosocysteine ethyl ester (SNCEE) rapidly inhibited
      DNA synthesis concomitant with Cdc25A loss. Surprisingly, this inhibition of DNA
      synthesis was refractory to ectopic expression of Cdc25A or a Cdc25-independent
      Cdk2 mutant. Nitrosative stress inhibited DNA synthesis without activating
      checkpoint signaling, thus distinguishing it from S-phase arrest mediated by
      other reactive *NO-derived species. The apparent lack of checkpoint activation
      was due to an active suppression because accumulation of pSer345-Chk1, pThr68
      Chk2 and gammaH2AX was inhibited by nitrosative stress in cells exposed to DNA
      damage or replication inhibitors. We speculate that failure to activate the S
      phase checkpoint in precancerous cells undergoing nitrosative stress may elevate
      the risk of transmitting damaged genomes to daughter cells upon cell cycle
      reentry.

PMID- 19158511
TI  - Autophagy in coxsackievirus-infected neurons.
AB  - Autophagy is a process to engulf aberrant organelles or protein aggregates into
      double-membrane vesicles for lysosomal breakdown. Autophagy is a protective
      process against some intracellular bacteria and viruses; however, it is also used
      for replication by some viruses, such as poliovirus. We recently found that
      coxsackievirus B4 (CVB4) also induces the autophagy pathway and activates the
      calpain system for replication in neurons. Notably, the inhibition of autophagy
      with 3-methyladenine (3MA) reduced calpain activation and virus replication.
      Calpain inhibitors also reduced autophagosome formation and virus replication.
      This finding indicates that calpain and the autophagy pathway are closely
      connected with each other during the infection. Interestingly, we also found that
      3MA and calpain inhibitors enhanced the caspase-3 specific cleavage of spectrin
      during CVB4 infection, suggesting that autophagy inhibition by these drugs
      triggered apoptosis. Thus, autophagy and apoptosis may balance each other in CVB4
      infected neurons. Here, we show that inhibition of caspase with zVAD increased
      autophagosome formation, further proposing the cross-talk between autophagy and
      apoptosis in CVB4-infected neurons.

PMID- 19158510
TI  - Dual functions of DNA replication forks in checkpoint signaling and PCNA
      ubiquitination.
AB  - During cell proliferation, DNA damage inflicted by intrinsic or extrinsic
      genotoxic stresses impose a threat to DNA replication. The stability of the DNA
      replication forks that encounter DNA damage is crucial for genomic integrity.
      Both the ATR-regulated checkpoint pathway and the translesion DNA synthesis
      mediated by the ubiquitinated PCNA are important for continuous replication of
      damaged DNA. We have recently shown that Chk1, a key effector kinase of ATR in
      checkpoint response, is required for efficient PCNA ubiquitination after DNA
      damage. Surprisingly, the ubiquitination of PCNA is independent of ATR, but
      regulated by Claspin, a replication protein that mediates the activation of Chk1
      by ATR. Like Claspin, Timeless and Rad17, two other Chk1 regulators at stressed
      replication forks, are also implicated in PCNA ubiquitination. These findings
      suggest that while ATR signaling and PCNA ubiquitination are two independent
      processes, they are mediated by a common group of proteins including Chk1 and it
      regulators at replication forks. Furthermore, these data raise the possibility
      that Chk1 and its regulators may constitute a functional module at replication
      forks to enable multiple stress responses.

PMID- 19158512
TI  - Reduction of caldesmon expression induces apoptosis and causes disassembly of the
      sarcomeric protein complex in cardiomyocytes in vivo.

PMID- 19158513
TI  - Case reports.

PMID- 19158516
TI  - The Peruvian fisherman's knot: a new, simple, and versatile self-locking sliding
      knot.
AB  - BACKGROUND: In many plastic surgery operations that are undertaken through
      relatively small incisions resulting in deep-seated operating fields, sliding
      knots with a self-locking property are preferred by plastic surgeons for 3
      reasons: simplicity, reliability, and versatility. We describe a new and
      versatile sliding knot that can be easily sledded and locked. METHODS: The
      technique of knot tying is described in detail as a stepwise approach with
      photographs. The main advantages of the Peruvian fisherman's knot are compared
      with other methods and summarized. RESULTS: In addition to its adjustment-related
      properties, knot security has been adequate with this knot as evidenced by its
      clinical performance and the authors' experiences to date. CONCLUSION: The
      Peruvian fisherman's knot is especially useful while working in deep seated
      operating fields through a small incision. Tension created during knot tying is
      adjustable, which makes it an ideal choice for various lifting procedures in
      plastic surgery.

PMID- 19158515
TI  - Measurement of aesthetic proportions in the profile view of Koreans.
AB  - We have evaluated the usefulness of direct soft tissue measurements in profile
      photographs for determining the nasal proportions and angles of young Korean
      individuals and those of rhinoplasty patients, and we compared these findings
      with existing norms of Caucasian populations. We retrospectively compared
      preoperative profile measurements of nasal length, nasal tip projection, dorsal
      height, radix height, nasolabial angle, and nasofrontal angle in 123 patients who
      underwent rhinoplasty, with measurements in 21 young Korean adults. Rhinoplasty
      patients were grouped by preoperative diagnosis as deviated nose without saddle
      or hump, saddle nose, hump nose, and low radix. The young Koreans had a nasal
      length to nasal tip projection to dorsal height to radix height ratio of
      2:0.97:0.61:0.28. Dorsal height differed significantly among groups of
      rhinoplasty patients. Those with low radix had the lowest dorsal and radix
      height, whereas those with saddle nose had the smallest nasal tip projection. The
      average nasolabial and nasofrontal angles were 78.5 degrees and 82.7 degrees,
      respectively, in young male Koreans and 126.0 degrees and 133.6 degrees,
      respectively, in young female Koreans. In the deviated nose group, all parameters
      except for nasofrontal angle were significantly changed after rhinoplasty. In the
      saddle nose group, nasal tip projection and dorsal height were significantly
      increased, whereas, in the hump nose group, nasal tip projection and nasolabial
      angle were significantly altered. Direct soft tissue measurement on profile
      photographs is useful for assessing nasal characteristics and postrhinoplasty
      outcomes. Compared with Caucasians, young Koreans had relatively lower dorsum and
      radix and more acute nasolabial angle, but similar nasofrontal angle.

PMID- 19158517
TI  - A prospective, multi-center study of psychosocial outcomes after augmentation
      with natrelle silicone-filled breast implants.
AB  - Psychosocial outcomes are believed to be a critical factor in determining the
      success of cosmetic surgery, but little research has focused on measuring these
      factors in breast augmentation patients. In the multicenter study for FDA
      approval of Natrelle silicone-filled breast implants, 455 augmentation patients
      completed paper and pencil measures of body image, self-esteem, and quality of
      life before implantation and at 1, 2, 4, and 6 years postimplantation. Subjects'
      satisfaction with their implants was uniformly high throughout the follow-up
      period, from 99% in the month after implantation to 95% at 6 years. Satisfaction
      with breast size, shape, and feel improved significantly postimplantation and
      continued through 6 years. Significant improvements in body image were found
      postoperatively and remained throughout the study. Improvements in health-related
      quality of life, however, were not observed. Results provide additional
      information on patient satisfaction and improvement in body image that typically
      occur after breast augmentation.

PMID- 19158518
TI  - Hyperprolactinemia and galactocele formation after augmentation mammoplasty.
AB  - Galactorrhea and galactocele formation are rare complications of augmentation
      mammoplasty. A number of case reports have been published in the literature;
      however, the etiology remains unclear. A case is presented of a unilateral
      galactocele associated with transient hyperprolactinemia after augmentation
      mammoplasty.

PMID- 19158519
TI  - Bilateral breast reconstruction using bilateral anterolateral thigh flaps: a case
      report.
AB  - Options for autologous reconstruction have been limited in some patients by
      previous abdominal surgeries, and by lack of adequate abdominal tissue. The
      anterolateral thigh (ALT) flap has previously been described as an alternate
      donor site for autologous breast reconstruction when abdominal tissue is
      unavailable or unsuitable.We describe our experience with a 41-year-old low body
      mass index (19.8 kg/m) patient with previous suction-assisted lipectomy underwent
      bilateral breast reconstruction using bilateral ALT flaps.At a follow-up of 2
      years, the patient was delighted with her reconstructed breasts and despite her
      athletic build was able to fill a B cup bra.ALT flap has the advantages of a long
      pedicle, adequate soft adipose tissue, and also allowing supine positioning with
      a 2-team approach. The anterolateral flap is a credible alternative that may be
      considered for bilateral autologous breast reconstruction in selected patients.

PMID- 19158520
TI  - Crystal deposition disease masquerading as proliferative tenosynovitis and its
      associated sequelae.
AB  - Extra-articular crystalline deposition secondary to gout, and less commonly,
      pseudogout is a well known phenomenon. Despite this well-documented entity of
      extra-articular deposition, there have been few reports of infiltration of the
      flexor tendon sheath of the hand. Here, we present a case series of this unique
      occurrence, including surgical techniques, pathology, and the clinical outcomes
      of 5 patients. We encountered 2 cases of calcium pyrophosphate and 3 cases of
      uric acid deposition into the flexor tendon sheath masquerading as common
      tendonopathies. These include cases of carpal tunnel syndrome, nonsuppurative
      flexor tenosynovitis, trigger finger, and attrition rupture of the flexor
      tendons. Although, medical therapy is the cornerstone of treatment for diseases
      that result in crystal deposition, these cases emphasize the potential need for
      surgical therapy in the armamentarium of their management. This case series
      demonstrates the importance of inclusion of crystal deposition into the flexor
      tendon sheath in the differential diagnosis in patients that present with
      uncharacteristic symptomatology of common flexor tendonopathies.

PMID- 19158521
TI  - Superficial temporal vessels as a reserve recipient site for microvascular head
      and neck reconstruction in vessel-depleted neck.
AB  - Reconstructions for local recurrence and second primary oromucosal cancer remain
      a challenge because the recipient vessels are depleted in the neck. The objective
      of this study was to investigate the outcome of superficial temporal vessels, as
      reserve recipient vessels for microvascular surgery in vessel-depleted neck
      patients. Between March 2003 and August 2005, the superficial temporal vessels
      were used as a recipient site for microsurgical head and neck reconstruction in
      15 patients with vessel-depleted necks. There was no flap loss in any of the
      reconstructions. One venous anastomosis was revised for thrombosis and flap
      salvaged. The superficial temporal vessels provide a good alternative for head
      and neck reconstruction in vessel-depleted neck patients with the advantages of
      radiation spared, constant anastomy, and suitable size. It obviates the need for
      long pedicle flaps or the use of vein grafts. Care must be taken not to damage or
      kink the vein.

PMID- 19158522
TI  - Cross-limb vascular shunting for major limb replantation.
AB  - In the management of traumatic major limb amputation, rapid re-establishment of
      circulation to the amputated part is imperative so as to prevent complications
      related to reperfusion injury, especially for those already suffering from
      prolonged ischemia. A temporary, extra-anatomic cross limb shunting with infusion
      lines can be used to perfuse the amputated part almost instantaneously. This
      allows the surgeon to carry out skeletal fixation and other reparative works in
      an unhurried manner. The cannulation site is targeted at intact vessels far away
      from the injury zone, obviating the need to explore and handle traumatized
      vessels at the mangled stump ends, thus greatly simplifying and expediting the
      revascularization process. Such a method had been successfully applied in 2 young
      people suffering traumatic arm amputation and thigh amputation, respectively. We
      suggested that such a procedure could be a useful adjunct in the field of major
      limb replantation.

PMID- 19158523
TI  - Head and neck malignant melanoma: margin status and immediate reconstruction.
AB  - Head and neck melanoma often approaches critical structures. Therefore, excision
      is often limited, leading to positive margins, and increased local recurrence.
      Immediate reconstruction carries concern for rearrangement or concealment of
      cancerous tissues. Therefore, reconstruction is often delayed until confirming
      negative margins on permanent pathology. Our purpose is to identify variables
      associated with a positive margin and establish criteria for reconstruction
      timing. We reviewed 117 consecutive patients who underwent wide local excision of
      head and neck melanoma. Reconstruction was immediate for 107 and delayed for 10.
      Six percent of patients had a positive margin after wide local excision with no
      difference in incidence between immediate and delayed reconstruction (P = 0.11).
      Tumor characteristics associated with a positive margin were locally recurrent,
      ulcerated, and T4 tumors (P < 0.05); and delayed reconstruction should be
      considered in these circumstances. Immediate reconstruction is safe for the
      majority of head and neck melanoma and should be based on knowledge of tumor
      characteristics.

PMID- 19158524
TI  - The subcutaneous cervicofacial flap revisited.
AB  - The cervicofacial flap has been the reconstruction of choice for midface soft
      tissue defects for over 30 years. Deep plane dissection has been advocated to
      decrease complication rates and improve results. However, the subcutaneous
      approach is still widely used. Over a 20-year period, we reviewed all patients
      who underwent subcutaneous cervicofacial flaps for cheek defects to analyze
      complications and results.Thirty-two patients (mean age, 71 years) underwent 32
      subcutaneous cervicofacial flaps for cheek reconstruction after Mohs micrographic
      excision of skin cancer. The mean defect size was 7.2 x 5.8 cm. Mean follow-up
      was 32 months. Only 3 of 32 patients (9%) had minor flap tip or edge necrosis,
      all managed without further surgery. One patient (3%) had minor long-term
      ectropion with upward gaze and 31 of 32 patients were happy with their
      results.The subcutaneous rotation-advancement cervicofacial flap remains an
      excellent choice for cheek reconstruction with comparable tip necrosis rates and
      likely lower ectropion rates when compared with the deep plane technique.

PMID- 19158525
TI  - Liquid nitrogen cryotherapy of lip mucosa hemangiomas under inhalation general
      anesthesia with sevoflurane in early infancy.
AB  - Mucous membrane hemangiomas of the lip are common benign vascular tumors of
      infancy. This clinical study evaluated the efficacy and safety of liquid nitrogen
      cryotherapy of mucous membrane hemangiomas of the lip in early infancy. It was a
      retrospective review of 127 pediatric patients with hemangiomas involving the
      lips who underwent liquid nitrogen cryotherapy under inhalation general
      anesthesia with sevoflurane. Forty-one males and 86 females were treated. The
      overall median age at diagnosis of the mucous membrane hemangiomas was 3.6 months
      (range, 7 days to 18 months). The oral mucous membrane hemangioma involved the
      vermilion of the lower lip in 78 cases (61.4%), the vermilion of the upper lip in
      40 cases (31.5%), and both vermilions in 9 cases (7.1%). No complications because
      of anesthesia occurred. The mean follow-up was 10 months, with a range of 8 to 14
      months; 94 lesions (74.0%) were completely involuted, 22 lesions (17.3%) were
      mostly involuted, 11 lesions (8.7%) were partially involuted, and no lesion
      showed a small amount of involution. Liquid nitrogen cryotherapy is an effective,
      simple, and safe treatment for mucous membrane hemangiomas of the lip in early
      infancy.

PMID- 19158526
TI  - Preoperative color Doppler assessment in planning of gluteal perforator flaps.
AB  - Gluteal artery perforator flaps have gained popularity due to reliability,
      preservation of the muscle, versatility in flap design without restricting other
      flap options, and low donor-site morbidity in ambulatory patients and possibility
      of enabling future reconstruction in paraplegic patients. But the inconstant
      anatomy of the vascular plexus around the gluteal muscle makes it hard to predict
      how many perforators are present, what their volume of blood flow and size are,
      where they exit the overlying fascia, and what their course through the muscle
      will be. Without any prior investigations, the reconstructive surgeon could be
      surprised intraoperatively by previous surgical damage, scar formation, or
      anatomic variants.For these reasons, to confirm the presence and the location of
      gluteal perforators preoperatively we have used color Doppler ultrasonography.
      With the help of the color Doppler ultrasonography 26 patients, 21 men and 5
      women, were operated between the years 2002 and 2007. The mean age of patients
      was 47.7 (age range: 7-77 years). All perforator vessels were marked
      preoperatively around the defect locations. The perforator based flap that will
      allow primary closure of the donor site and the defect without tension was
      planned choosing the perforator that showed the largest flow in color Doppler
      ultrasonography proximally. Perforators were found in the sites identified with
      color Doppler ultrasonography in all other flaps. In our study, 94.4% flap
      viability was ensured in 36 perforator-based gluteal area flaps. Mean flap
      elevation time was 31.9 minutes. We found that locating the perforators
      preoperatively helps to shorten the operation time without compromising a
      reliable viability of the perforator flaps, thus enabling the surgeon easier
      treatment of pressure sores.

PMID- 19158527
TI  - Outpatient reconstruction using integra* and subatmospheric pressure.
AB  - Integra (Integra Lifesciences Corporation, Plainsboro, NJ) has been used in a
      variety of reconstructive surgical procedures. The application of Integra using
      subatmospheric pressure (V.A.C., Kinetic Concepts, Inc, San Antonio, TX) has been
      suggested to be easier, faster, and more consistent than previous dressings,
      allowing grafting as soon as 1 week after Integra placement. Ten patients were
      chosen for outpatient reconstructive surgery with Integra and subatmospheric
      pressure with skin grafting 7-10 days (mean = 8 days) post-Integra. Skin graft
      take was 75% to 100% (mean = 91.5%). No patients required additional grafting or
      reconstruction. Integra may be successfully used for reconstruction of difficult
      areas as an outpatient in combination with subatmospheric pressure (V.A.C.). This
      allows for expedited treatment, decreased morbidity, and lower cost versus
      standard Integra application.

PMID- 19158528
TI  - Modified tibial turn-up fillet flap for repair of extensive composite defects of
      the thigh.

PMID- 19158529
TI  - Marjolin ulcer arising within hidradenitis: a case report and literature review.
AB  - This is a report of a patient with squamous cell carcinoma discovered in a bed of
      longstanding (>20 years) hidradenitis suppurativa. A literature search
      demonstrates this to be an entity with potentially devastating sequelae if not
      expediently diagnosed and treated. In light of the possibility of malignant
      transformation, the hidradenitis specimen and any suspicious lesions in proximity
      should be sent to pathology for thorough assessment.

PMID- 19158530
TI  - Nasal reconstruction after severe facial burns using a local turndown flap.
AB  - Reconstruction of the nose after severe burn injury is a challenging problem.
      There are usually associated facial burns, which limits the availability of local
      flaps. Reconstruction with unburned distant tissue is often not appropriate
      because of the resulting mismatch in color and texture. Successful nasal
      reconstruction can be accomplished in this group of challenging patients using a
      simple, inferiorly based flap from the nasal dorsum with subsequent skin grafting
      to the resulting defect. We have used an inferiorly based nasal turndown flap to
      reconstruct severe nasal deformities after burn injury in 28 patients. The flap
      tissue consists of the dorsal surface of the nose, which is usually made up of
      skin graft and scar. The flap base is the scar transition zone between the dorsum
      of the nose and the lining mucosa. This is turned over to provide nasal length,
      projection, and to stimulate alar lobules. The resulting defect on the dorsum of
      the nose is then skin grafted. If further length or refinement is required, the
      procedure may be repeated. The records of all patients who underwent this
      procedure were reviewed for demographics, age at burn, percentage of total body
      surface area burned (%TBSA), availability of the forehead, number of procedures,
      and complications. Twenty-eight patients underwent nasal reconstruction in our
      series using this local turndown flap. Most of these patients had severe burns,
      with an average %TBSA of 46%. The procedure was initially applied to patients
      with devastating injuries and %TBSA of 80%-95%, with extremely limited donor
      sites. As the success of the procedure was established, less severely burned
      patients were included in the series, thereby lowering the mean %TBSA. All
      patients had partial or complete destruction of their forehead donor site. All
      patients presented for multiple hospitalizations, with an average of 17 hospital
      admissions. Using this local turndown flap, adequate nasal length and projection
      could be achieved. There were few complications. All of the flaps survived,
      although there were 2 cases of necrosis of the distal edge of the flaps (0.7%).
      This resulted in decreased length and projection but this problem was
      successfully addressed with additional staged procedures. Contraction of local
      scar tissue created bulk and support, eliminating the need for distant tissue
      transfer or cartilage grafting. Twelve of the 28 patients required repeat
      turndown flaps to achieve sufficient nasal length and projection. These results
      were durable over a follow-up period of up to several decades. A simple,
      multistaged dorsal nasal flap can be used to reconstruct severe nasal deformities
      after facial burn injury. This can obviate the need for distant tissue transfer.
      Even in patients with subtotal nasal amputation and complete absence of
      cartilaginous support, the opportunistic use of scar tissue can restore nasal tip
      projection and alar lobule architecture without cartilage grafting. The resulting
      nasal reconstruction blends well into the surrounding facial appearance. This
      simple technique has been remarkably successful in this selected group of
      patients with challenging nasal deformities.

PMID- 19158531
TI  - Intracellular adenosine triphosphate delivery enhanced skin wound healing in
      rabbits.
AB  - Small unilamellar lipid vesicles were used to encapsulate adenosine triphosphate
      (ATP-vesicles) for intracellular energy delivery. This technique was tested in
      full-thickness skin wounds in 16 adult rabbits. One ear was rendered ischemic by
      using a minimally invasive surgery. The other ear served as a normal control.
      Four circular full-thickness wounds were created on the ventral side of each ear.
      ATP-vesicles or saline was used and the wounds were covered with Tegaderm (3M,
      St. Paul, MN). Dressing was changed and digital photos were taken daily until all
      the wounds were healed. The mean healing times of ATP-vesicles-treated wounds
      were significantly shorter than that of saline-treated wounds on ischemic and
      nonischemic ears. Histologic study indicated better-developed granular tissue and
      reepithelialization in the ATP-vesicles-treated wounds. The wounds treated by ATP
      vesicles exhibited extremely fast granular tissue growth. More CD31 positive
      cells were seen in the ATP-vesicles-treated wounds. This preliminary study shows
      that direct intracellular delivery of ATP can accelerate the healing process of
      skin wounds on ischemic and nonischemic rabbit ears. The extremely fast granular
      tissue growth was something never seen or reported in the past.

PMID- 19158532
TI  - Selection and effect of ointment bases for preparing collagenase inhibitor
      ointment using high-performance liquid chromatography and Franz cell apparatus.
AB  - After the dorsal subcutaneous administration of injectable collagen implant
      derived from bovine dermis (Zyderm; INAMED, Santa Barbara, CA) to mice, ointments
      that contain 3 types of collagenase inhibitors, Esculetin (6,7-dihydroxy-2H
      chromen-2-one), ONO-4817 [(2S,4S)-N-hydroxy-5-ethoxymethyloxy-2-methyl-4-(4
      phenoxybenzoyl) amino-pentanamide], and MMI270 (CGS27023A) {N-hydroxy-2(R)-[(4
      methoxysulfonyl)-(3-picolyl)-amino]-3-methylbutanamide hydrochloride monohydrate}
      were applied daily on the dorsal region of mice (injection site), and intradermal
      Zyderm was extirpated after 30, 60, and 90 days to measure the level of
      hydroxyproline. Furthermore, dermal tissue was examined by Azan staining and
      immunostaining. A significant difference was observed in the level of
      hydroxyproline in the Esculetin and the ONO-4817 ointment groups compared with
      that in the control group after 30 days. A significant difference was also
      observed in the level of hydroxyproline in the Esculetin ointment group compared
      with that in the control group after 60 and 90 days. Histologically, 90 days
      after the application of the ointment, dense localization of type III collagen
      was observed around the injected Zyderm in the group applied Esculetin ointment
      compared with the control group. Therefore, it was indicated that Esculetin
      suppressed the degradation of collagen, and further facilitated the qualitative
      changes that increased neo-collagen, and that the collagen implant with
      hypodermic injection remained on behalf of ointments contained within the
      collagenase inhibitors that were applied on the skin surface.

PMID- 19158533
TI  - The effect of vitamin C on ischemia reperfusion injury because of prolonged
      tourniquet application with reperfusion intervals.
AB  - We examined the effect of vitamin C on muscle injury distal to the tourniquet
      which was applied for 4 hours with 10- and 20-minute reperfusion intervals after
      2 hours of tourniquet. Sixty-four Sprague-Dawley rats were allocated to 4
      randomized groups. After 2 hours tourniquet, 10- and 20-minutes of reperfusion
      were allowed to half of each group respectively. Afterward an additional 2 hours
      compression was applied. Except the control group the animals received vitamin C
      intravenously, before the first tourniquet in Group I, at the reperfusion
      interval in Group II, and at both times in Group III. Malondialdehyde levels were
      measured in blood and the tibialis anterior muscle. The muscle was
      histopathologically examined. The data was evaluated statistically. The effects
      of timing and the dose of vitamin C on ischemia reperfusion injury remain
      controversial and there was no statistical difference between 10- and 20-minute
      reperfusion intervals. But the blood malondialdehyde levels showed that vitamin C
      has a positive effect on the muscle injury caused by ischemia-reperfusion.

PMID- 19158534
TI  - Mathematical calculations in a spherical tissue expander.

PMID- 19158535
TI  - Pectus excavatum reconstruction with silicone implants: long-term results and a
      review of the english-language literature.
AB  - Pectus excavatum, or funnel chest, is an anterior chest wall deformity,
      characterized by a depressed sternum. Frequently used techniques for pectus
      excavatum repair are extensive thoracic surgical corrections at a young age. At
      an adult age, custom-made silicone implants can be used as a less extensive
      surgical option. Thus far, there are only a limited number of reports in the
      English-language literature concerning this treatment modality. We evaluated our
      series of 16 patients treated with custom-made silicone implants, assessing
      complications, patient satisfaction, and aesthetic outcome. Seven patients (44%)
      had complications, mostly seroma formation (31%). Ten of 12 patients (83%), who
      were evaluated at the long-term, reported improved patient satisfaction and 9 of
      13 patients (69%), in whom aesthetic results were assessed, had a good or
      excellent aesthetic outcome.Our study, combined with a review of the English
      language literature, demonstrates that there is a place for custom-made silicone
      implants in the treatment of pectus excavatum, especially in less severe cases at
      an adult age. Preoperative counseling with emphasis on the likelihood of seroma
      formation is advocated.

PMID- 19158536
TI  - Odontogenic keratocyst: an unusual location and review of the literature.
AB  - Odontogenic keratocyst is an epithelial developmental odontogenic cyst most
      commonly occurring in the jaws. It comprises approximately 11% of all cysts of
      the jaws. It has an aggressive behavior including high rates of recurrence, rapid
      growth, and extension into adjacent tissues. Odontogenic keratocyst is commonly
      found in the mandible with a predilection for angle and ascending ramus of the
      mandible. We document a case of odontogenic keratocyst that is unusually
      originated from the temporomandibular joint and we review the existing literature
      concerning odontogenic keratocyst. As far we know this is the first case of the
      odontogenic keratocyst originating from the temporomandibular joint.

PMID- 19158537
TI  - Desmoid tumors of the pediatric mandible: case report and review.
AB  - Desmoid tumors are benign fibrous neoplasms originating from the
      musculoaponeurotic structures throughout the body. These rare neoplasms have been
      shown to account in 0.03% of all cancers. Twenty-five percent of all desmoid
      tumors occur in children under 15 years of age. The infrequency of these tumors
      has limited studies to case reports and retrospective reviews dictating the
      authors recommended treatments and management. We present a case report of
      desmoid tumor involving the left mandible in a 14-month-old infant. His treatment
      course included 2 excisions, removal of the free rib graft secondary to
      persistence of the tumor, and wound dehiscence, and later a free fibular
      osteomyocutaneous flap for reconstruction. We then retrospectively reviewed all
      published data of desmoid tumor involving the pediatric mandible since 1950 to
      2007 in the PubMed database. Forty cases have been reported, which had a M:F
      ratio of 1:1 with an average age of 5.3 (standard deviation [SD] +/- 4.5) years.
      There appeared to be left-sided predominance of desmoid tumors in the pediatric
      mandible with a ratio of 3:1. The mean size of the tumors was 4.6 cm (SD +/- 2.1)
      at the largest diameter. We have tabulated the relevant data of all the cases
      including the methods of treatment and recurrence. It is found that when compared
      with conservative management, radiation therapy, chemotherapy, and curettage or
      surgical local excisions as treatment options the most efficient treatment was
      partial mandiblectomy, which resulted in complete tumor dissipation with no tumor
      recurrence. In summary, this is the largest review of the pediatric desmoid tumor
      of the mandible to date where we provide for the first time an algorithm for the
      management and treatment of the pediatric desmoid tumor of the mandible.

PMID- 19158538
TI  - A modified approach to sural nerve biopsy: minimizing complications.
AB  - The traditional sural nerve biopsy is performed through a distal incision at or
      just above the ankle. Although a simple procedure, these biopsies are associated
      with significant morbidity. The authors review the anatomy of the sural nerve,
      biopsy techniques described in the literature, and potential complications. A
      modified approach, based on a more proximal incision, and its outcomes are
      described.

PMID- 19158539
TI  - The role of IL-8 in patients with fibromyalgia: a prospective longitudinal study
      of 6 months.
AB  - OBJECTIVE: In this prospective longitudinal clinical study, we evaluated the role
      of proinflammatory cytokine IL-8 and its clinical relevance in patients with
      fibromyalgia (FM) who fulfilled clearly defined inclusion and exclusion criteria
      and underwent a 3-week inpatients multidisciplinary pain therapy. METHODS: IL-8
      in sera was measured in 20 patients with FM and 80 healthy participants at 4
      fixed time points: at the beginning of the study, at 10 days, 21 days, and 6
      months, respectively. Pain intensity, back function, depression, nicotine/alcohol
      consumption, and medication were assessed in the patient group and correlated
      with IL-8 levels. RESULTS: Before and during the inpatient therapy, the serum
      level of IL-8 was significantly higher in patients with FM compared with controls
      (P<0.001), but did not correlated with pain intensity and medication. Already at
      T1 there was a significant reduction of IL-8 serum level (P=0.023) in patient
      group. Six months after multidisciplinary pain therapy, IL-8 serum level in FM
      patients was still significantly higher than controls (P=0.044) but reduced
      approximately to normal range and correlated significantly negatively with pain
      intensity (r=-0.782, P=0.001). Patients with FM had significantly less pain
      (P<0.001) and better back function (P<0.001) at day 2 than at day 0. In addition,
      in patients with FM, IL-8 serum level correlated with nicotine consumption
      (r=0.471, P=0.042). CONCLUSIONS: Our results suggest that IL-8 level contributes
      in patients with FM whose pain intensity and back function can be improved under
      influence of multidisciplinary pain therapy without need of an anti-IL-8 therapy.

PMID- 19158540
TI  - Characteristics of patients with acute low back pain presenting to primary care
      in Australia.
AB  - OBJECTIVES: This study aimed to provide a comprehensive profile of a
      representative sample of patients with acute low back pain drawn from the primary
      care setting. A secondary aim was to determine whether patient characteristics
      are associated with pain intensity or disability at the initial consultation.
      METHODS: A total of 1172 consecutive patients with acute low back pain presenting
      to clinics of primary care practitioners (general practitioners,
      physiotherapists, and chiropractors) in Australia were recruited. Pain intensity
      and level of disability were measured at the first consultation, and a range of
      other variables were measured to describe the patient's characteristics. The
      characteristics were then grouped into 7 distinct factors: demographic, social,
      cultural, general health, psychologic, past low back pain history, and current
      low back pain history. Hierarchical linear regression models were used to
      determine each factor's independent relationship with pain intensity and
      disability. RESULTS: The majority of patients reported having had a previous
      episode of low back pain (75.7%), and that the current episode was of sudden
      onset (76.7%). Only a small proportion (14.3%) had compensable back pain. Pain
      intensity and disability were associated with each other (P<0.01), current low
      back pain history (P<0.01), and psychologic (P<0.01) characteristics. DISCUSSION:
      In a representative sample of acute low back pain patients in primary care, we
      found that the profile included only a small proportion of patients with
      compensable low back pain. Those without compensation were more likely to remain
      at work despite low back pain. Psychologic and other patient characteristics were
      associated with pain intensity and level of disability at the initial
      consultation.

PMID- 19158541
TI  - High and low frequency TENS reduce postoperative pain intensity after
      laparoscopic tubal ligation: a randomized controlled trial.
AB  - BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is an effective
      adjunctive therapy for postoperative pain; however, effects of different
      frequencies of stimulation have not been systematically investigated.
      Laparoscopic sterilization (LS) causes significant pain in the early
      postoperative period and requires substantial postoperative medication.
      Therefore, we studied the effects of TENS on postoperative pain after LS through
      placement of Yoon fallopian rings in a prospective, randomized, double-blinded,
      and placebo-controlled study. METHODS: Sixty-four patients undergoing LS for
      uterine tube ligation were randomly allocated to receive either active TENS or
      placebo TENS. Postoperative pain was evaluated using a standard 11-point numeric
      rating scale and the McGill Pain Questionnaire (MPQ)-pain rating index and number
      of words chosen. Both high frequency (100 Hz) and low frequency (4 Hz) TENS, at
      strong, but comfortable sensory intensity, were applied for 20 minutes through 4
      electrodes placed around the surgical incision immediately after surgery. Pain
      was assessed before and after application of TENS when patients were at
      postanesthesia care unit (PACU). RESULTS: Both high and low frequency TENS
      significantly decreased postoperative pain intensity when compared with before
      administration of TENS using the numeric rating scale (P=0.001), pain rating
      index (P=0.001), and number of words chosen (P=0.001) compared with placebo TENS
      (P=0.001). TENS in combination with standard pharmacologic analgesic treatment
      was efficacious for postoperative pain relief after LS. CONCLUSIONS: We recommend
      regular use of multimodal therapy with TENS and analgesic drugs after LS with
      placement of Yoon rings.

PMID- 19158542
TI  - A Cross-cultural Study of the Back Pain Beliefs of Female Undergraduate
      Healthcare Students.
AB  - OBJECTIVES: To determine if country (Australia, Taiwan, Singapore), undergraduate
      healthcare course (physiotherapy, nursing), low back pain (LBP) history, and year
      of course influenced various back pain beliefs in undergraduate female healthcare
      students. METHODS: Three hundred and 82 female undergraduate nursing and
      physiotherapy students completed questionnaires examining; the inevitability of
      future life with low back trouble, the LBP beliefs held by healthcare providers
      and fear avoidance beliefs related to physical activity. Also participants
      completed questionnaires to determine their LBP status. General linear models
      were used to determine whether differences existed for back beliefs scores.
      RESULTS: Differences were evident in the future consequence of LBP between
      countries (P<0.001), undergraduate course (P<0.001), and LBP status (P=0.021).
      Healthcare provider beliefs were found to be significantly influenced by course
      only (P<0.001). Fear avoidance beliefs related to physical activity were
      influenced by country (P=0.002) and undergraduate course (P<0.001). When compared
      with white Australians, Taiwanese and Singaporean Chinese displayed more negative
      back beliefs regarding the future consequence of LBP (P<0.001) and more fear
      avoidant beliefs toward physical activity (P=0.021 and P<0.001, respectively).
      Further, nursing students had more negative back pain beliefs than physiotherapy
      students (P<0.001) and, the experience of LBP was associated with more positive
      beliefs on the future consequence of back trouble (P=0.021). DISCUSSION: Findings
      of this study highlight the importance of country, education, and LBP experience
      on back pain beliefs. The more negative back pain beliefs found in Taiwan and
      Singapore may reflect current pain beliefs and management attitudes.

PMID- 19158543
TI  - How to apply the ICF and ICF core sets for low back pain.
AB  - OBJECTIVE: To introduce the International Classification of Functioning,
      Disability and Health (ICF) as conceptual model and classification and the ICF
      Core Sets as a way to specify functioning for a specific health condition such as
      Low Back Pain, and to illustrate the application of the ICF and ICF Core Sets in
      the context of clinical practice, the planning and reporting of studies and the
      comparison of health status measures. METHODS: A decision-making and consensus
      process was performed to develop the ICF Core Sets for Low Back Pain, the linking
      procedure was applied as basis for the content comparison of health-status
      measures and the Rehab-Cycle was used to exemplify the application of the ICE and
      ICF Core Sets in clinical practice. RESULTS: Two different ICF Core Sets, namely,
      a comprehensive and a brief, are presented, three different health-status
      measures were linked to the ICF and compared and a case example of a patient with
      Low back Pain was described based on the Rehab-Cycle. DISCUSSION: The ICF is a
      promising new framework and classification to assess the impact of Low Back Pain.
      The ICF and practical tools, such as the ICF Core Sets for Low Back Pain, are
      useful for clinical practice, outcome and rehabilitation research, education,
      health statistics, and regulation.

PMID- 19158544
TI  - Impact of tobacco use in patients presenting to a multidisciplinary outpatient
      treatment program for fibromyalgia.
AB  - OBJECTIVES: This study examined the relationship between the severity of
      fibromyalgia symptoms and current tobacco use in patients evaluated at a
      specialized fibromyalgia treatment program. METHODS: Demographic and clinical
      data from 984 consecutive patients evaluated at the Mayo Clinic Fibromyalgia
      Treatment Program including the Fibromyalgia Impact Questionnaire (FIQ) were
      prospectively collected and stored in an electronic medical record and an
      electronic database. Univariate analyses were performed comparing tobacco users
      and nonusers. A post-hoc analysis of covariance was conducted for tobacco use,
      using group differences of confounding clinical and demographic variables. A P
      value < or = 0.05 was accepted as the level of significance. RESULTS: One hundred
      and forty-five patients were identified as tobacco users (14.7%). Tobacco use was
      associated with greater pain intensity as measured by pain scales and the pain
      component of the FIQ. Tobacco users had a greater FIQ composite score 70.0(15.1)
      versus 61.8(16.8), P<0.001. By univariate analysis, tobacco users had higher
      scores on all the FIQ components and fewer good days and more days of work missed
      per week. Tobacco use was associated with several confounding clinical and
      demographic variables including lower education, higher unemployment, not being
      married or widowed, and history of abuse. After adjusting for these confounding
      variables, tobacco users continued to have greater pain intensity, a higher total
      and component FIQ scores except for fatigue. Smoking was not associated with a
      higher number of tender points. DISCUSSION: Current tobacco use was associated
      with more severe fibromyalgia symptoms in patients presenting to a specialized
      fibromyalgia treatment program.

PMID- 19158545
TI  - "Nerve combing" for trigeminal neuralgia without vascular compression: report of
      10 cases.
AB  - OBJECTIVES: The purpose of this study was to describe and evaluate the
      contributions of "nerve combing" to trigeminal neuralgia (TN) without vascular
      compression. METHODS: Ten of 96 cases with TN who intended to be treated with
      microvascular decompression in our clinic had no visible vascular compression
      intraoperatively. The operative procedure for all 10 patients was nerve
      combining. RESULTS: At least 3 years after surgery, 7 of 10 patients were pain
      free after nerve combing. One patient had little pain relief. One patient
      experienced significant partial relief, and the intensity of the residual pain in
      this patient was not severe enough to require medication. Recurrence occurred in
      1 case 18 months postoperatively. Permanent sensory deficits were present in 1
      patient. CONCLUSIONS: Minimal trigeminal nerve root trauma via nerve combining
      technique demonstrated a beneficial impact on TN within this cases series.
      Further studies should be carried out to explore the possible mechanisms of
      underlying pain and to assess outcomes with respect to currently available
      medical and surgical treatment options.

PMID- 19158546
TI  - Two brief versions of the multidimensional pain readiness to change
      questionnaire, version 2 (MPRCQ2).
AB  - OBJECTIVES: The present study sought to develop 1-item and 2-item versions of
      subscales from the Multidimensional Pain Readiness to Change Questionnaire,
      Version 2 (MPRCQ2), a measure of readiness to adopt a variety of pain management
      and coping strategies commonly taught in multidisciplinary treatment programs.
      METHODS: One hundred and ninety patients with rheumatic diseases who entered a
      Rheumatology Day Program completed the MPRCQ2 and an additional criterion
      measure, the Pain Stages of Change Questionnaire (PSOCQ), before and after
      treatment. First one and then a second item that best represented each MPRCQ2
      scale were selected based on: (1) the correlations between the items and their
      parent MPRCQ2 scale; (2) responsivity to change following treatment; (3)
      correlations of the items with the PSOCQ scales; and (4) authors' consensus of
      face validity and construct representativeness of items. The psychometric
      properties of the 1-item and 2-item versions of the MPRCQ2 scales were then
      examined. RESULTS: These brief versions provided good approximations of their
      parent scales and 9/10 were responsive to change following multidisciplinary
      treatment. Correlations between the brief scales and the PSOCQ scales showed
      similar relationships as with the full MPRCQ2 scales. DISCUSSION: The findings
      support the validity of these brief versions of the MPRCQ2 subscales. We would
      recommend the use of these versions of the MPRCQ2 when a measure of patient
      readiness to use a range of pain self-management coping strategies is needed (eg,
      treatment process research, prediction of success in multidisciplinary
      treatment), but response burden is a significant issue.

PMID- 19158547
TI  - Agreement of parents and children on characteristics of pediatric headache, other
      pains, somatic symptoms, and depressive symptoms in an epidemiologic study.
AB  - BACKGROUND: The objective of the present study was to assess the concordance
      between parent and child report regarding different domains of pediatric health,
      headache in particular. In addition, the influence of potential moderator
      variables on the agreement between parents and children was examined.
      METHODOLOGY: In an epidemiologic study on a randomly drawn sample of households
      with at least 1 child in the family between 7 and 14 years of age (community
      registries), various pediatric health disturbances (headache, other pains,
      somatic symptoms, and depression/anxiety) were assessed via both child (from the
      age of 9 y on) and parent report (n=3461). RESULTS: A relatively high parent
      child agreement (sigmaM=0.61) was found regarding the variable headache
      frequency, whereas consensus regarding other pains was, for the most part,
      markedly lower. The lowest agreement (sigmaM=0.27) was found for
      depression/anxiety symptoms. A moderator analysis (with age, sex, and parental
      headache) between child and parent failed to reveal significant differences
      regarding the degree of agreement between the 2 data sources. Children reported
      more frequent and more severe symptoms in all health domains. CONCLUSION: The
      examined potential moderator variables did not elucidate processes underlying the
      differences in child and parent agreement. There is no convincing evidence that
      the children's appraisal is less valid than their parents'. In summary, parents'
      reports cannot be viewed as a substitute for children's reports in pediatric pain
      and health assessment. Instead, each perspective represents a unique subjective
      reality and as such, both are of importance for research on pediatric pain and
      other health variables.

PMID- 19158548
TI  - Statistical validation of the relationships of cancer pain relief with various
      factors using ordered logistic regression analysis.
AB  - OBJECTIVE: To clarify the relationships of cancer pain with various factors that
      prevent pain control statistically. METHODS: The participants were 71 terminal
      cancer patients admitted to the Department of Hematology/Oncology or Department
      of Gastroenterology/Hepatology, University Hospital, Kyoto Prefectural University
      of Medicine in whose pain control a pharmacist was involved as part of her
      clinical duties from January 2004 to November 2006. The effectiveness of pain
      control was evaluated using a 5-point verbal rating scale (0=excellent, 1=good,
      2=moderate, 3=poor, and 4=very poor) by interviewing the patients. As pain was
      rated using a graded scale and as many factors were involved in pain, analysis
      was performed using ordered logistic regression analysis. Moreover, prediction of
      an optimal model was performed by leave-one-out cross-validation to eliminate
      unnecessary variables. A program to perform leave-one-out cross-validation by
      ordered logistic regression analysis was prepared, independent variables used in
      the model were increased one by one, and calculation was performed in all
      combinations. Then, the optimal model was predicted by calculating the percent
      accuracy of predictions and Spearman rank correlation coefficient. RESULTS:
      Nausea [odds ratio (OR)=1.948, P=0.0232], sex (OR=2.322, P=0.0030), and bone
      metastasis (OR=2.367, P=0.0017) remained as variables significantly correlated
      with pain when the number of independent variables was 5, and sex (OR=2.167,
      P=0.006) and bone metastasis (OR=2.093, P=0.005) remained when the number of
      variables was 6. DISCUSSION: The statistical identification of factors preventing
      pain control is considered to contribute to the establishment of an evidence
      based approach to cancer pain relief.

PMID- 19158549
TI  - Utility and application of urine drug testing in chronic pain management with
      opioids.
AB  - OBJECTIVES: Important scientific principles of pain medicine pharmacology affect
      urine drug testing (UDT). This paper reviews sources of variability in
      pharmacokinetics, pharmacodynamics, pharmacogenetics, and issues relating to the
      collection, handling, and assay of urine and how these factors may affect test
      interpretation and application. METHODS: Articles concerning the
      pharmacokinetics, pharmacodynamics, and pharmacogenetics of opioids are reviewed
      and interpreted for pain clinicians who treat patients with chronic opioid
      therapy. These data are applied to the use of UDT. RESULTS: Intraindividual and
      interindividual variability in drug metabolizing enzyme activity due to genetic
      polymorphisms or environmental effects can result in day-to-day and patient-to
      patient variability in drug exposure. Transporters, also under genetic and
      environmental control, can play an important role in opioid response and
      contribute to the significant variability in opioid pharmacokinetics and
      response. The use of urine creatinine concentration to adjust urine drug
      concentrations, discussion of UDT assays, and application of UDT in light of an
      understanding of pharmacokinetics, pharmacodynamics, and pharmacogenetics are
      reviewed. In addition, the methodology used for testing has an important role in
      accuracy. Because of these factors, UDT cannot be used to determine patient
      compliance with a specific opioid dose. DISCUSSION: UDT, when used with an
      understanding of the principles of pharmacokinetics, pharmacodynamics, and
      pharmacogenetics of opioids, can be a useful tool in chronic pain management.
      Clinicians must keep in mind the limitations, purpose, and value of UDT, and the
      inability to predict patient compliance with a drug dosage using commercial
      algorithms.

PMID- 19158550
TI  - Reliability of physical examination for diagnosis of myofascial trigger points: a
      systematic review of the literature.
AB  - BACKGROUND: Trigger points are promoted as an important cause of musculoskeletal
      pain. There is no accepted reference standard for the diagnosis of trigger
      points, and data on the reliability of physical examination for trigger points
      are conflicting. OBJECTIVES: To systematically review the literature on the
      reliability of physical examination for the diagnosis of trigger points. METHODS:
      MEDLINE, EMBASE, and other sources were searched for articles reporting the
      reliability of physical examination for trigger points. Included studies were
      evaluated for their quality and applicability, and reliability estimates were
      extracted and reported. RESULTS: Nine studies were eligible for inclusion. None
      satisfied all quality and applicability criteria. No study specifically reported
      reliability for the identification of the location of active trigger points in
      the muscles of symptomatic participants. Reliability estimates varied widely for
      each diagnostic sign, for each muscle, and across each study. Reliability
      estimates were generally higher for subjective signs such as tenderness (kappa
      range, 0.22-1.0) and pain reproduction (kappa range, 0.57-1.00), and lower for
      objective signs such as the taut band (kappa range, -0.08-0.75) and local twitch
      response (kappa range, -0.05-0.57). CONCLUSIONS: No study to date has reported
      the reliability of trigger point diagnosis according to the currently proposed
      criteria. On the basis of the limited number of studies available, and
      significant problems with their design, reporting, statistical integrity, and
      clinical applicability, physical examination cannot currently be recommended as a
      reliable test for the diagnosis of trigger points. The reliability of trigger
      point diagnosis needs to be further investigated with studies of high quality
      that use current diagnostic criteria in clinically relevant patients.

PMID- 19158551
TI  - Keratoconus associated with other corneal dystrophies.
AB  - OBJECTIVE: To report the concomitant presentation of keratoconus and corneal
      dystrophies at Wills Eye Hospital for the 10-year period from January 1, 1997, to
      December 31, 2006. METHODS: Patients with concomitant keratoconus and corneal
      dystrophies were identified using a computer database. Complete ophthalmologic
      examination, keratometry, pachymetry, and computerized videokeratography were
      performed in all patients. When present, cornea guttata were confirmed by
      clinical examination and specular microscopy. Histopathologic examination with
      special stains of excised corneal buttons was performed. RESULTS: Fifty-one
      patients manifested typical signs and topographic evidence of keratoconus
      associated with another corneal dystrophy. Fuchs dystrophy was the most common
      association accounting for 27 cases (52.9%), followed by anterior basement
      membrane dystrophy with 13 cases (25.5%) and posterior polymorphous dystrophy
      with 7 cases (13.8%). A bilateral combination of Fuchs dystrophy and anterior
      basement membrane dystrophy with keratoconus was seen in 3 cases (5.8%). Finally,
      there was 1 bilateral case (2%) of granular dystrophy. Histopathologic studies in
      cases that underwent penetrating keratoplasty confirmed the clinical diagnoses.
      CONCLUSION: To our knowledge, this is the largest report of such a concurrence in
      the English literature and could lead to further studies on the possible
      pathophysiologic or genetic links between these entities, although a chance
      association cannot be excluded.

PMID- 19158552
TI  - Age-related differences in central corneal thickness alterations caused by short
      term hypobaric hypoxia.
AB  - PURPOSE: To assess the effect of short-term hypobaric hypoxic exposure on central
      corneal thickness (CCT) in healthy participants in 2 different age groups.
      METHODS: Seventy eyes in 35 healthy men were investigated. Twenty participants
      (mean age 22.8 +/- 0.6 years) comprised 1 group, and 15 (mean age 32.1 +/- 2.8
      years) comprised another group. CCT was measured via ultrasound pachymetry
      initially at local ground level (792 m above sea level), then during short-term
      hypobaric hypoxic exposure (equivalent to 9144 m altitude), and then again under
      ground level conditions. The mean of 10 consecutive CCT measurements in each eye
      under each set of conditions was used in statistical analysis. RESULTS: In the
      younger group, initial CCT was 561.5 +/- 36.1 microm. This increased to 562.3 +/-
      36.7 microm under hypobaric hypoxic conditions, and after the return to local
      ground level conditions, CCT decreased to 560.1 +/- 34.5 microm. CCT values under
      hypobaric hypoxic conditions were not significantly different from those measured
      before or afterward (P > 0.05). In the older group, initial CCT was 566.0 +/-
      33.7 microm. This increased to 576.9 +/- 28.5 microm under hypobaric hypoxic
      conditions, and after the return to local ground level conditions, CCT decreased
      to 567.9 +/- 33.3 microm. In the older group, CCT values under hypobaric hypoxic
      conditions were significantly greater than those measured initially (P < 0.001)
      or afterward (P < 0.01). In both age groups, initial CCT did not differ
      significantly from final CCT (P > 0.05). CONCLUSION: Short-term hypobaric hypoxic
      exposure increased CCT significantly in the older age group, whereas it yielded a
      nonsignificant minor increase in the younger age group.

PMID- 19158553
TI  - Deep anterior lamellar keratoplasty with melles technique for granular corneal
      dystrophy.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical results of deep
      anterior lamellar keratoplasty (DALK) using the Melles technique in granular
      corneal dystrophy. METHODS: Seven eyes from 5 patients who underwent DALK using
      Melles technique for granular corneal dystrophy were included in this study. The
      parameters evaluated included patients' demographics, preoperative and
      postoperative best spectacle-corrected visual acuities (BSCVAs), and timing and
      pattern of recurrence. RESULTS: The mean age of the patients was 37 +/- 9.4 years
      (range 29-46 years) at the time of surgery. The mean length of follow-up (DALK to
      last visit) was 38.4 +/- 18.6 months (range 10-63 months). The procedure was
      performed without any major complication in all eyes. Mean preoperative BSCVA was
      20/220 (range 20/400 to 20/100), which improved to 20/27 (range 20/30 to 20/25)
      at 6 months after DALK. Mean BSCVA was 20/50 (range 20/400-20/20) at last follow
      up. Simple recurrence occurred in 5 (71%) of 7 eyes. The mean time from surgery
      to recurrence was 15.6 +/- 1.8 months (range 13-16 months). Clinically
      significant recurrences occurred 34 +/- 2 months after the procedures in 3 (43%)
      of 7 eyes. Two (30%) of 7 eyes had no recurrence at all. CONCLUSIONS: Although
      granular corneal dystrophy is likely to recur after DALK, this technique can
      restore and preserve useful visual function for a significant period in these
      patients.

PMID- 19158554
TI  - Excimer laser phototherapeutic keratectomy for keratoconus nodules.
AB  - PURPOSE: To report the outcomes of contact lens-intolerant patients with
      keratoconus (KCN) with subepithelial nodules treated with excimer laser
      phototherapeutic keratectomy (PTK). METHODS: The charts of all contact lens
      intolerant patients with KCN who underwent excimer laser PTK for subepithelial
      nodules were identified using a computer database and were retrospectively
      reviewed. Preoperative and postoperative visual acuity and method of correction,
      surgical treatment, epithelial healing, complications, and KCN nodule recurrence
      were all analyzed. RESULTS: Fifteen eyes of 15 patients with a minimum follow-up
      of 3 months were reviewed. Mean follow-up time was 23.1 months (SD +/- 42.5
      months, range 3-143 months). In 9 eyes, the epithelial defect healed by
      postoperative day 3 and all eyes healed by postoperative day 6. There was no
      infection or corneal melting in any of the eyes. After PTK, 11 patients were
      refit successfully with rigid gas-permeable contact lenses and 4 wore glasses.
      Three patients had a recurrence of the KCN nodule at 3, 8, and 23 months
      postoperatively. One of them had a repeat PTK 23 months after the initial
      surgery, improving to 20/40 with contact lenses at 55 months postoperatively.
      Another patient decided to have a penetrating keratoplasty, and the third patient
      is considering repeat PTK or penetrating keratoplasty. CONCLUSION: PTK
      effectively removed KCN nodules without recurrences in most patients and can be a
      successful modality to improve contact lens tolerance and delay or avoid more
      invasive surgery.

PMID- 19158555
TI  - Agreement between stratus and visante optical coherence tomography systems in
      tear meniscus measurements.
AB  - AIM: To compare the tear meniscus height (TMH) measurements provided by the
      Stratus and Visante optical coherence tomography systems. METHODS: A cross
      section image of the lower tear meniscus was captured with both instruments in 26
      volunteers. An external application was used to manually measure the TMH as
      imaged by the Stratus; measurements by the Visante were analyzed by the internal
      software. Only 1 eye for each subject was considered for statistical analysis.
      RESULTS: The mean (+/-SD) TMH was higher when measured by the Visante (0.28 +/-
      0.12 mm) compared with the Stratus (0.23 +/- 0.07 mm, P = 0.029). Measurements
      were correlated (R = 0.38, P = 0.0008), but Bland-Altman analysis showed low
      agreement (95% limits of agreement: -0.15 to +0.26 mm). CONCLUSIONS: Visante and
      Stratus cannot be used interchangeably to measure the TMH. The differences
      between the 2 instruments are likely to be related both to the dynamic nature of
      the tear meniscus and to the distortion of Stratus images, which are not dewarped
      and calibrated for anterior segment imaging.

PMID- 19158556
TI  - Diamond burr polishing for recurrent corneal erosions: results from a prospective
      randomized controlled trial.
AB  - PURPOSE: To evaluate the use of diamond burr polishing as an in-office treatment
      for recurrent corneal erosion (RCE). METHODS: A double-masked randomized
      controlled trial was conducted. Patients with RCE secondary to trauma or anterior
      basement membrane dystrophy underwent epithelial debridement (ED) or diamond burr
      superficial keratectomy (DBSK) at the slit lamp. Patients were followed up for 6
      months, and the recurrence rates of RCE and visual outcomes were compared.
      RESULTS: Forty-eight eyes of 48 patients were recruited. The mean +/- SD age was
      38.3 +/- 12.9 years. Twenty-five patients underwent DBSK, and 23 patients
      received ED alone. There was no significant difference in the baseline
      demographics between the 2 groups. Kaplan-Meier survival analysis showed
      significantly less major and minor recurrences and less need for repeated
      surgical interventions in the DBSK group compared with the ED group (P < 0.001).
      Eyes in the DBSK group also had significantly lower mean magnitude of astigmatism
      after treatment compared to the ED group (P = 0.021). CONCLUSION: Diamond burr
      polishing is a safe, convenient, and inexpensive treatment option for the
      management of RCE and resulted in better outcomes compared to simple epithelial
      debridement.

PMID- 19158558
TI  - Microbial keratitis in patients with down syndrome: a retrospective study.
AB  - PURPOSE: To study the microbiological and clinical profile of cases of microbial
      keratitis in patients with Down syndrome. METHODS: A retrospective chart review
      of all patients with Down syndrome and microbial keratitis admitted to the Royal
      Victorian Eye and Ear Hospital, Melbourne, Australia, between January 1997 and
      January 2007 was undertaken. Main parameters evaluated were clinical and
      microbiological profile and final outcome. RESULTS: Of 18 patients included in
      this study, 11 were men and 7 were women, with mean age of 50 +/- 29 years (range
      20-61 years). The most common associated ocular abnormality was eyelid diseases
      (94%) followed by atopic keratoconjunctivitis (44%). Positive microbiological
      cultures were obtained in 5 (28%) cases with Streptococcus pneumoniae being the
      most prevalent isolate. Ocular herpes was detected in 2 patients with polymerase
      chain reaction. Surgical intervention was required in 13 (72%) patients in the
      form of keratoplasty (n = 3) corneal gluing (n = 2), tarsorrhaphy (n = 5), botox
      injection (n = 1), and enucleation (n = 2). CONCLUSIONS: Microbial keratitis in
      Down syndrome is associated with eyelid problems and ocular atopy, and due to
      failure of medical therapy alone, surgical intervention is required in majority
      of cases.

PMID- 19158557
TI  - Complex deep lamellar endothelial keratoplasty for complex bullous keratopathy
      with severe vision loss.
AB  - PURPOSE: To determine the efficacy and postoperative complications of complex
      deep lamellar endothelial keratoplasty (DLEK) when used for the management of
      complex bullous keratopathy with severe vision loss. METHODS: Twelve consecutive
      eyes with severe bullous keratopathy and other associated intraocular
      abnormalities underwent complex DLEK which was combined with other intraocular
      surgeries such as vitrectomy, intraocular lens removal, and secondary intraocular
      lens implantation. An air bubble was used in 9 eyes and an air and C3F8 gas
      bubble in 3 eyes for tissue support. Prospective data of best spectacle-corrected
      visual acuity, corneal astigmatism, and curvature were collected on all 12 eyes
      preoperatively and at 6, 9, and 12 months postoperatively. Average donor
      endothelial cell density was recorded preoperatively and at 9 months
      postoperatively. RESULTS: Preoperatively, severe visual loss was recorded at hand
      motions (n = 3), count fingers (n = 7), and 20/400 (n = 2). Best spectacle
      corrected visual acuity improved in 83% of eyes with vision of 20/67 or better in
      42% (5/12) and 20/100 or better in 66% (8/12) of eyes at 12 months
      postoperatively. Vision was not improved in three eyes due to coexistent retinal
      disease. Four aphakic eyes underwent secondary intraocular lens implantation
      later at 4-6 months after DLEK, and best spectacle-corrected visual acuity was
      increased from count fingers to 20/200 or better. At 12 months postoperatively,
      average corneal astigmatism and curvature were 2.3 +/- 0.5 diopters and 44.0 +/-
      0.9 diopters, respectively. Average central corneal thickness at 12 months
      postoperatively (541.3 +/- 26.7 microm) was significantly thinner than that
      before surgery (673.8 +/- 77.5 microm, P < 0.01). Preoperative average donor
      endothelial cell density was 2685.1 +/- 193.9 cells/mm. At 9 months
      postoperatively, average endothelial cell density was 1920.1 +/- 94.0 cells/mm
      (27.3% of endothelial cell loss) in eyes with primary surgery and 1866.3 +/- 92.8
      cells/mm (33.9% of endothelial cell loss) in eyes with secondary surgery.
      Postoperative complications usually occurred within 3 months of surgery. After
      surgery, 3 eyes showed narrow gaps between the border of the graft and the host.
      Epithelial bullae in these areas recurred in 2 eyes but disappeared within 3
      months. There was one graft dislocation in this series, no pupillary block cases,
      and no primary graft failures. CONCLUSIONS: In cases of complex bullous
      keratopathy with severe vision loss, DLEK combined with other intraocular
      surgeries is a feasible and effective procedure to significantly improve visual
      acuity to a functional level in most patients. DLEK can be used successfully in
      eyes with aphakia and other anterior segment abnormalities without a high risk of
      graft dislocation or failure. Mild postoperative complications usually occurred
      early after DLEK and did not affect visual outcomes and graft survival if managed
      appropriately.

PMID- 19158559
TI  - Prospective study on the safety and efficacy of combined conjunctival rotational
      autograft with intraoperative 0.02% mitomycin C in primary pterygium excision.
AB  - PURPOSE: To describe the novel use of combined conjunctival rotational autograft
      (CRA) and intraoperative 0.02% mitomycin C (MMC) in the treatment of primary
      pterygium and to evaluate its safety and efficacy. METHODS: Prospective
      interventional case series comparing with historical controls was conducted.
      Patients with primary pterygium underwent pterygium excision, MMC was applied to
      the scleral bed after the surface conjunctiva was harvested, and the CRA was
      sutured back with a 180-degree rotation. Patients were followed for a minimum of
      1 year. RESULTS: Sixty-seven eyes from 67 patients participated in the study, of
      which 31 (46.3%) were men and 36 (53.7%) were women. The mean age was 58 +/- 10.6
      years, (range 36-79 years). There were 2 recurrences (3%), one occurring at month
      3 and the other at month 9. Compared with historical controls, CRA-MMC resulted
      in significantly fewer recurrences than MMC alone (P = 0.005) when adjusted for
      age and was equally effective when compared with limbal-conjunctival autografts.
      The main postoperative problem was graft injection, which was noted in 41 eyes
      (61%) at 1 year. CONCLUSIONS: To the best of our knowledge, this was the first
      study on the combined use of CRA and MMC in the treatment of primary pterygium.
      CRA with MMC was found to be effective in the prevention of recurrence. Although
      injection remained as a cosmetic concern, it was a safe alternative to limbal
      conjunctival autograft in cases where mobilizing autologous conjunctival tissue
      would not be feasible.

PMID- 19158560
TI  - Fibrin glue-assisted augmented amniotic membrane transplantation for the
      treatment of large noninfectious corneal perforations.
AB  - PURPOSE: To evaluate and report the efficacy of fibrin glue (FG)-assisted
      augmented amniotic membrane transplantation (AMT) in patients with large corneal
      perforations. METHODS: In a retrospective case series, 10 patients with corneal
      perforations more than 2 mm in diameter were treated with "FG-assisted augmented
      AMT." A 5- or 7-ply "augmented amniotic membrane" (AM) was constructed by
      applying FG to each sheet of AM to repair the corneal perforation. The augmented
      AM was designed 0.5 mm larger than the diameter of the perforation. The augmented
      AM was transplanted onto the perforation site with 10-0 nylon suture. If needed,
      additional overlay AM was sutured on top. RESULTS: The mean ulceration diameter
      was 2.7 +/- 0.95 mm (range, 2-5 mm). All patients retained their own globes after
      the procedure and had well-formed deep anterior chambers, and 90% of patients
      showed complete epithelialization over the AM. The mean reepithelialization time
      was 14.9 +/- 4.9 days (range, 10-24 days). No eyes showed evidence of infection
      or recurrent corneal melting during the follow-up period. CONCLUSIONS: FG
      assisted augmented AMT was easily performed for repairing large corneal
      perforations. This surgical method was very helpful in stabilizing the wound in
      the early postoperative period.

PMID- 19158562
TI  - Eyelid pressure: inferences from corneal topographic changes.
AB  - PURPOSE: It is known that eyelid pressure can influence the corneal surface.
      However, the distribution of eyelid pressure and the eyelid contact area and the
      biomechanics of the changes are unknown. Although these factors are difficult to
      directly measure, analysis of eyelid-induced corneal topographic changes and
      eyelid morphometry enables some inferences to be drawn. METHODS: Eighteen
      subjects, aged between 19 and 29 years, with normal ocular health were recruited.
      Corneal topographic changes were measured after 4 conditions consisting of 2
      downward gaze angles (20 and 40 degrees) and 2 types of visual tasks (reading and
      steady fixation). Digital photography recorded the width of Marx line, the
      assumed region of primary eyelid contact with the cornea. RESULTS: Significantly
      larger corneal changes were found after the 40-degree downward gaze conditions
      compared with 20-degree conditions because of the upper eyelid contact (P <
      0.001). For the 40-degree downward gaze tasks, the lower eyelid changes were
      greater than those because of the upper eyelid (P < 0.01). The upper eyelid Marx
      line width was associated with the amplitude of corneal change (R = 0.32, P <
      0.05). CONCLUSIONS: Analysis of the corneal topographic changes gives insight
      into the pressure applied by the upper and lower eyelids in different situations.
      These include greater upper eyelid pressure with increasing downward gaze and
      greater lower eyelid pressure compared with the upper eyelid in 40-degree
      downward gaze. There was some evidence that supports Marx line as the primary
      site of contact between the eyelid margins and the cornea.

PMID- 19158561
TI  - Characterization of the thinnest point of the cornea compared with the central
      corneal thickness in normal subjects.
AB  - INTRODUCTION: For ongoing progress in refractive surgery, exact knowledge about
      the anatomical properties of the cornea is useful. Thus, the aim of the study was
      to characterize the thinnest point of the cornea compared with the central
      corneal thickness in normal subjects and to investigate with regard to
      influencing factors such as sex, age, refraction, and intraocular pressure.
      MATERIALS AND METHODS: The central corneal thickness and the thinnest point of
      the cornea were determined with the Orbscan II in 390 white normal subjects.
      Difference between the 2 eyes, influence of sex, and measuring repetition
      accuracy were tested for statistical significance with t tests, and the influence
      of age was tested with nonparametrical test methods. RESULTS: In the right eyes,
      the mean central corneal thickness was 548 +/- 37 microm and the thinnest point
      537 +/- 37 microm. In the left eyes, the mean central corneal thickness was 547
      +/- 37 microm and the thinnest point 535 +/- 39 microm. The difference between
      the central corneal thickness and the thinnest point was found to be significant
      in both eyes in paired t test (P > 0.001). No influence of sex, refraction, and
      intraocular pressure on the thickness of the thinnest point of the cornea could
      be observed. The difference between central corneal thickness and thickness at
      the thinnest point was not subject to a statistically significant influence of
      age. CONCLUSIONS: In the calculation of the residual corneal layer thickness in
      laser refractive surgery, the thinnest point of the cornea should form the basis.

PMID- 19158563
TI  - Elevated tear interleukin-6 and interleukin-8 levels in patients with
      conjunctivochalasis.
AB  - PURPOSE: To determine the interleukin (IL)-6 and IL-8 levels in the tear samples
      of patients with conjunctivochalasis (CCh) and to correlate the severity of
      symptoms with tear IL levels. METHODS: Fifty-one eyes at different stages of CCh
      and 10 eyes of healthy controls were recruited for this prospective study
      undertaken at a single university-based hospital. CCh was graded based on the
      extent of inferior lid margin involvement as follows: 1 = single (temporal)
      location, 2 = 2 locations, and 3 = whole lid. The presence of punctal occlusion
      and fluorescein clearance patterns were recorded. Enzyme-linked immunosorbent
      assay was used to determine IL levels. Severity of symptoms was assessed with the
      ocular surface disease index. RESULTS: Of the 51 study patients (mean age = 63.4
      +/- 6.9 years), 16 had grade 1, 21 had grade 2, and 14 had grade 3 CCh. Tear IL-6
      and IL-8 levels were significantly higher in patients with CCh than in controls
      (P <or= 0.001). Higher IL levels were observed in grades 2 and 3 CCh than in
      grade 1 CCh and control eyes (P < 0.001). Patients with CCh who also had punctal
      occlusion and delayed fluorescein clearance results had higher tear IL levels
      than those who did not (P <or= 0.001). Tear IL levels were positively correlated
      with the clinical severity of CCh as evaluated with the ocular surface disease
      index (r = 0.826, P < 0.001 for IL-6 and r = 0.726, P < 0.001 for IL-8).
      CONCLUSIONS: Inflammation may have a role in the pathogenesis of CCh. The
      clinical severity of CCh parallels the increased tear IL levels. Markers for
      inflammation are more pronounced in the advanced stages of this disease.

PMID- 19158564
TI  - Expression pattern of connexins in the corneal and limbal epithelium of a
      primate.
AB  - PURPOSE: To detect the expression pattern of connexins in epithelial cells of the
      central cornea and limbus of the macaque. METHODS: Total RNA was extracted from
      the central corneal and limbal epithelia of Macaca fascicularis and processed by
      reverse transcriptase-polymerase chain reaction with isoform primers to detect
      the expression of 16 connexin (Cx). Immunofluorescent staining of frozen sections
      of corneal tissue confirmed and localized connexin proteins expression. RESULTS:
      Transcripts encoding 10 Cx isoforms (Cx26, Cx30, Cx30.3, Cx31, Cx31.1, Cx32,
      Cx43, Cx45, Cx50, and Cx58) were detected by reverse transcriptase-polymerase
      chain reaction in both central and peripheral corneal epithelium. Six (Cx26,
      Cx31, Cx32, Cx43, Cx45, and Cx58) were confirmed by laser scanning confocal
      microscopy. Cx26 was detected throughout the central corneal epithelium and in
      the mid and superficial layers of the limbal epithelium. Cx43 and Cx45 were
      localized to the basal and suprabasal epithelial cells. Cx58 was expressed in the
      superficial epithelium throughout the cornea, whereas Cx31 and Cx32 were mainly
      expressed in the central corneal epithelium and weakly in the limbal area.
      CONCLUSIONS: The complex distribution pattern of the connexins suggests that
      selected isoforms play important roles in maintaining corneal homeostasis.

PMID- 19158565
TI  - Time- and temperature-dependent stability of growth factor peptides in human
      autologous serum eye drops.
AB  - PURPOSES: To develop a step-by-step production method for human autologous serum
      (AS) eye drops that was broadly compliant with US Food and Drug Administration
      requirements for reinjection of processed biological substances. To determine
      optimum storage conditions for AS eye drops by measuring the concentration of
      growth factor peptides (GFP) as a function of storage temperature and storage
      duration. METHODS: AS derived from the blood of 3 healthy male volunteers was
      produced using a closed, vacuum-driven, cascade-filtration system under sterile,
      low-pyrogen conditions. In-process controls included methods for monitoring
      protein electrophoretic mobility and degradation rate and the content of free
      hemoglobin and endotoxin. Stability of transforming growth factor beta1,
      substance P, nerve growth factor, calcitonin gene-related peptide, insulin-like
      growth factor 1, and epidermal growth factor was evaluated at -15 degrees C, +4
      degrees C, +25 degrees C, +37 degrees C, and +42 degrees C at different time
      intervals (hours to weeks). The main outcome measures were the concentrations of
      GFP, endotoxin, and lipid peroxidation by-products (a proxy measure for protein
      degradation) in dilute AS. RESULTS: The stability of GFP varies: transforming
      growth factor beta1, nerve growth factor, epidermal growth factor, and insulin
      like growth factor 1 were more temperature and time resistant, but substance P
      and calcitonin gene-related peptide significantly degraded at +4 degrees C in 24
      hours. Endotoxin and lipid peroxidation by-products were not significantly
      increased by processing. CONCLUSIONS: This pilot study developed a closed,
      cascade-filtration system that was an effective method for the production of high
      quality, low-pyrogen AS. The processing method broadly complied with Food and
      Drug Administration requirements for reinjection of biological substances.
      Variable GFP stability was observed at +4 degrees C and above. For clinical use,
      AS should be packaged in daily-use containers, which should be stored frozen; the
      container in active use should be refrigerated between doses.

PMID- 19158566
TI  - Short-term effect of topical dorzolamide hydrochloride on intrastromal corneal
      pressure in rabbit corneas in vivo.
AB  - PURPOSE: To evaluate the effect of topical dorzolamide on the intrastromal
      corneal pressure (ICP) in rabbit corneas in vivo. METHODS: This is an
      interventional prospective study. Topical dorzolamide was applied to 7 eyes of 7
      male New Zealand rabbits 3 times daily for 3 consecutive days. The ICP changes
      were recorded with a pressure transducer connected to the midperipheral cornea.
      The ICP was measured in the same manner in 7 eyes of 7 male New Zealand rabbits
      that were treated with artificial tears (control group). RESULTS: The ICP values
      averaged -6.2 +/- 3.2, -10 +/- 5.8, and -12.5 +/- 8.7 mm Hg at 15, 30, and 45
      minutes in the control group, respectively. In the dorzolamide-treated eyes, the
      ICP readings were 1.8 +/- 3.4, -0.28 +/- 4.3, and -1.8 +/- 5.3 mm Hg at the same
      time points, respectively. The differences in the ICP between both groups were
      significantly different at all time points (P = 0.004, P = 0.005, and P = 0.02).
      CONCLUSIONS: Measuring ICP is a valid and sensitive method to evaluate in vivo
      the endothelial function. This method seems to be more sensitive than measuring
      the central corneal thickness or the corneal deswelling rate in detecting changes
      in the corneal physiology with the use of topical dorzolamide.

PMID- 19158567
TI  - Femtosecond-assisted anterior lamellar corneal staining-tattooing in a blind eye
      with leukocoria.
AB  - PURPOSE: To describe the technique and a case report of femtosecond-assisted
      anterior lamellar corneal staining-tattooing in a blind eye with leukocoria.
      METHODS: An anterior lamellar corneal free flap (thickness: 120 microm, diameter:
      7.0 mm) was created using femtosecond laser (IntraLase-AMO, Irvine, CA). The free
      flap was removed and immersed in a commercially available black tattoo pigment.
      After 9 minutes of flap incubation with the tattoo pigment solution, the flap was
      continuously irrigated for 3 minutes with balanced salt solution (Alcon
      Laboratories, Fort Worth, TX) until all the excessive pigment was removed. The
      flap was repositioned on the residual corneal bed, and a bandage contact lens was
      placed. RESULTS: : There were no intraoperative or postoperative adverse events
      seen by the 6-month follow-up, although an excellent cosmetic result was
      achieved. CONCLUSIONS: : The technique of FALT is simple and efficient for
      treating cosmetically blind eyes with leukocoria and may overcome the limitations
      of previously reported techniques. The long-term safety of the commercially
      available corneal tattoo dyes should be studied further.

PMID- 19158568
TI  - Flipping the inverted donor disk in descemet stripping automated endothelial
      keratoplasty.
AB  - We describe a technique we used to flip the donor corneal lenticule during
      Descemet stripping automated endothelial keratoplasty. In this case, in which we
      performed standard phacoemulsification and intraocular lens implantation as a
      combined procedure with Descemet stripping automated endothelial keratoplasty,
      the donor lenticule unfolded upside down in the anterior chamber (AC). To flip
      the donor to a stromal side up position with minimum manipulation, we first
      passed in a needle and fixed it on the edge of the lenticule. This needle was
      used to push the edge of the lenticule upward while we filled up the AC with
      balanced salt solution, directing the fluid to push the distal edge down and
      away. Having flipped the lenticule halfway, the procedure was continued by
      placing the needle on the midperipheral stroma of the donor lenticule and sliding
      it toward the recipient cornea. Then, the AC was filled with air to allow
      adhesion of the donor, and at the end of surgery, the air was replaced with
      balanced salt solution. The cornea cleared over a period of 10 days after
      surgery. At the end of the fourth postoperative week, the final best-corrected
      visual acuity was 20/50.

PMID- 19158569
TI  - The use of voriconazole in the treatment of cylindrocarpon keratomycosis.
AB  - PURPOSE: To describe a rare form of fungal keratitis due to Cylindrocarpon
      lichenicola. METHOD: A 56-year-old woman presented with an atypical corneal ulcer
      that did not respond to broad- spectrum antibiotics. RESULTS: Additional
      diagnostic tests such as confocal microscopy and corneal biopsy were useful aids
      in establishing the diagnosis of fungal keratitis. The ulcer healed completely
      after the initiation of antifungal therapy. CONCLUSIONS: To the best of our
      knowledge, this is the first case of C. lichenicola keratomycosis in the United
      Kingdom. Our case demonstrates that prompt recognition and effective treatment of
      this condition can lead to a good visual outcome.

PMID- 19158570
TI  - MoisturePlus contact lens solution as a source of acanthamoeba keratitis.
AB  - Recently, it was suggested that the use of the Advanced Medical Optics Complete
      MoisturePlus multipurpose cleaning solution might be a risk factor for
      contracting Acanthamoeba keratitis, and the manufacturer voluntarily recalled it
      in May 2007. Polymerase chain reaction amplification and sequencing of a variable
      part of the 18S rRNA gene allowed for the first time tracking of Advanced Medical
      Optics Complete MoisturePlus-associated Acanthamoeba keratitis isolate from a
      patient back to the lens cleaning solution itself.

PMID- 19158571
TI  - Limbal stem cell deficiency arising from systemic chemotherapy with
      hydroxycarbamide.
AB  - PURPOSE: The purpose of this study was to report a case of limbal stem cell
      deficiency (LSCD) after systemic chemotherapy with hydroxycarbamide. METHODS:
      Clinical manifestations and pathology are detailed. RESULTS: We describe the case
      of a woman with sickle cell disease, who developed bilateral LSCD after treatment
      with hydroxycarbamide. Histologic examination confirmed the diagnosis of LSCD,
      revealing goblet cells, inflammatory cells, deposits of new collagen components,
      and neovascularization in the peripheral cornea. Matrix metalloproteinase-3,
      fibronectin, and collagen III were also detected in the lesions. CONCLUSIONS: The
      systemic use of the antineoplastic drug, hydroxycarbamide, may cause severe LSCD.
      We recommend that a medication history, including that of cytotoxic drugs, be
      considered in evaluating LSCD.

PMID- 19158573
TI  - Donor-to-host transmission of Candida glabrata to both recipients of corneal
      transplants from the same donor.
AB  - PURPOSE: To report 2 cases of exogenous Candida glabrata endophthalmitis after
      penetrating keratoplasty in recipients of corneas from the same donor
      transplanted on the same day. METHODS: Case reports with ophthalmologic, electron
      microscopic, and microbiological findings including fungal strain analysis.
      RESULTS: Two patients developed fungal keratitis and endophthalmitis caused by
      the same C. glabrata strain within 1 day after penetrating keratoplasty of
      corneas from the same donor on the same day. Donor-to-host transmission was
      postulated when eye bank sterility checks were repeatedly negative. CONCLUSIONS:
      A short death-to-harvesting time, routine donor rim cultures, and respecting of a
      time interval before transplantation may provide an additional safety feature in
      dealing with corneal tissue from high-risk donors.

PMID- 19158572
TI  - Fabry disease and chemosis.
AB  - PURPOSE: To report the case of a patient with Fabry disease (FD) whose ocular
      presentation with chronic chemosis we feel is related to FD and to describe the
      conjunctival fluorescein angiographic findings. METHODS: A 51-year-old male
      patient with FD on enzyme replacement therapy presented with 1-month chemosis and
      mild irritation in the left eye. Ocular examination revealed pronounced
      noninflammatory chemosis inferotemporally in the left eye with conjunctival
      tortuosity and microaneurysms bilaterally. There was mild corneal verticillata,
      spoke-like lens opacities, and retinal vascular tortuosity bilaterally, with no
      evidence of disc or macular edema. Evaluation revealed no systemic cause for his
      chemosis, including an orbital computerized tomography scan, which showed clear
      sinuses and no evidence of an intraorbital mass. RESULTS: Conjunctival
      fluorescein angiography revealed rapid subconjunctival accumulation of dye in the
      involved eye but failed to demonstrate leakage from tortuous conjunctival vessels
      or microaneurysms. CONCLUSIONS: Although the pathology of chronic chemosis in
      patients with FD is as yet unknown, we believe that FD should be considered in
      the differential diagnosis of patients presenting with chronic chemosis of
      unknown etiology.

PMID- 19158574
TI  - Blueberry eye: acquired total anterior staphyloma after a fungal corneal ulcer.
AB  - PURPOSES: The purposes of this study were to report the presentation and
      management of an acquired total anterior staphyloma that resulted from a fungal
      corneal ulcer and to discuss its pathogenesis. METHODS: Observational case
      report. Clinical observation and surgical intervention of a patient who developed
      a total anterior staphyloma after a partially treated fungal corneal ulcer.
      RESULTS: The patient presented with a large traumatic fungal ulcer but was poorly
      compliant with follow-up and medications. He subsequently presented with a large
      total anterior staphyloma that resulted from perforation of the ulcer with
      plugging of the defect with iris and formation of a pseudocornea over the iris.
      The anterior staphyloma measured 15 x 16 mm and progressed to a stage where the
      patient was unable to close his eyelids and required a sclerokeratoplasty.
      Currently, vision is poor from amblyopia and a cloudy graft; however, the eye is
      intact and comfortable. CONCLUSIONS: Anterior staphylomas usually result from
      untreated fungal ulcers in developing nations. Poor compliance with medications
      and follow-up was the cause of our patient's anterior staphyloma.
      Sclerokeratoplasty can restore the globe structurally but has poor visual
      prognosis.

PMID- 19158575
TI  - Ocular surface reconstruction in graft-versus-host disease with HLA-identical
      living-related allogeneic cultivated limbal epithelium after hematopoietic stem
      cell transplantation from the same donor.
AB  - PURPOSE: To report a case of HLA-identical allogeneic living-related ex vivo
      expanded limbal epithelium in ocular surface reconstruction for chronic graft
      versus-host disease (cGVHD). METHODS: Review the clinical findings in a 58-year
      old woman with bilateral limbal stem cell deficiency caused by cGVHD who
      underwent ocular surface reconstruction on the left eye with cultivated limbal
      epithelial cells (LECs) on intact human amniotic membrane combined with
      extracapsular cataract extraction and intraocular lens implantation. LECs were
      harvested from a small biopsy of the same HLA-identical living-related donor who
      already donated peripheral blood cells for hematopoietic stem cell
      transplantation. RESULTS: At the present state, after a follow-up of 31 months,
      the patient shows a successful ocular surface reconstruction with a clear,
      smooth, and stable corneal ocular surface without recurrence of limbal stem cell
      deficiency. Nine months postoperatively, patients' corneal thinning progressed to
      a small perforation, which was successfully treated with a tectonic perforating
      keratoplasty combined with the removal of irritating lid lashes. CONCLUSION: The
      technique of HLA-typed allogeneic ex vivo expansion of LECs harvested from the
      same living-related donors who already donated hematopoietic stem cells offers a
      possibility to reconstruct ocular surface in cGVHD.

PMID- 19158576
TI  - Corneal ectasia after laser in situ keratomileusis after laser thermal
      keratoplasty.
AB  - PURPOSE: To report a case of corneal ectasia following hyperopic laser in situ
      keratomileusis in a patient who had previous laser thermal keratoplasty. METHODS:
      Case report. RESULTS: We report a case of a 66-year-old emmetropic man initially
      presented with complaint of difficulty reading without correction. Laser thermal
      keratoplasty (LTK) was performed on the non-dominant right eye, resulting in
      successful monovision. Three years later, the patient presented with decreased
      unaided near vision caused by hyperopic regression of the LTK. Conventional
      hyperopic laser in situ keratomileusis (LASIK) was performed, again resulting in
      successful monovision. More than three years later, the patient returned with
      worsening near vision. A focal corneal ectasia was noted in the same location as
      the 6 o'clock LTK leukoma. CONCLUSIONS: To our knowledge, this is the first
      report of ectasia occuring after LASIK following LTK. Consideration should be
      given to performing photorefractive keratectomy (PRK) instead of LASIK following
      thermal keratoplasty.

PMID- 19158577
TI  - Traumatic graft dehiscence after anterior lamellar keratoplasty.
AB  - A 64-year-old man underwent anterior lamellar keratoplasty using the Melles
      technique for corneal scar secondary to healed bacterial keratitis in the left
      eye. Two months postoperatively, the patient presented with blurry vision in the
      left eye after a fall in the bathroom. The uncorrected visual acuity was 20/400
      in the left eye, and the external examination showed periorbital swelling with
      ecchymosis. Slit-lamp examination revealed an absent graft, a circular crater in
      the center, and a fragment of suture on the temporal edge of the crater. The
      Seidel test was negative, and there was no sign of infection. The anterior
      segment optical coherence tomography showed intact residual stroma with slight
      forward protrusion. The patient underwent repeat anterior lamellar corneal
      transplantation with improvement in uncorrected visual acuity of 20/100 and best
      spectacle-corrected visual acuity of 20/70 in the left eye 3 months
      postoperatively.

PMID- 19158578
TI  - Use of anterior segment optical coherence tomography to assess secondary glaucoma
      after penetrating keratoplasty.
AB  - PURPOSE: To describe the use of anterior segment optical coherence tomography (AS
      OCT) in the evaluation of a patient with raised intraocular pressures after
      penetrating keratoplasty. METHODS: A 52-year-old Indian male with bilateral
      keratoconus underwent multiple penetrating keratoplasties because of repeated
      episodes of endothelial rejection and graft failure. He also had secondary
      glaucoma bilaterally for which he underwent bilateral posterior implantation of
      glaucoma drainage device. During the early postoperative period after a repeat
      right penetrating keratoplasty with anterior synechiolysis, his right intraocular
      pressure was persistently raised. The AS-OCT was used to aid in the assessment of
      the patient. RESULTS: The AS-OCT showed obstruction of the glaucoma drainage
      device by iris tissue and enabled precise placement of the iridectomy immediately
      overlying the tube orifice. CONCLUSIONS: The AS-OCT is a useful investigative
      tool that enables a better evaluation of the structures within the AS. The
      noncontact nature of the AS-OCT also makes it suitable in postpenetrating
      keratoplasty eyes where undue pressure on the corneal graft should be avoided.

PMID- 19158579
TI  - Bevacizumab (avastin) for corneal neovascularization--corneal light shield soaked
      application.
AB  - PURPOSE: To describe a case where topical bevacizumab (Avastin) was used in an
      attempt to reduce corneal neovascularization before corneal graft. METHODS:
      Topical bevacizumab was applied through a corneal light shield for 20 minutes
      once a week for 11 weeks to the cornea. RESULTS: Corneal vascularization was not
      reduced. CONCLUSIONS: Topical bevacizumab was not effective in this case at
      reducing corneal neovascularization.

PMID- 19158581
TI  - A review of lipid management in primary and secondary prevention.
AB  - Lipid management in primary and secondary prevention reduces cardiovascular
      morbidity and mortality. Lowering of low-density lipoprotein cholesterol (LDL-C)
      levels with statins remains the primary goal of therapy. For secondary prevention
      patients, those with coronary heart disease (CHD) or CHD risk equivalents,
      intensive LDL-C lowering is recommended, although the precise target value is
      still debated. For primary prevention, reduction in LDL-C levels is based on
      patient risk for CHD. In clinical outcome trials to date, statins benefit those
      who are at moderate to high risk and appear to have less clinical benefit for
      those at low risk. Yet despite aggressive LDL-C management with statins, there
      remains a residual risk for CHD events in high-risk patients. Secondary targets
      have been proposed to decrease this risk, including non-high-density lipoprotein
      cholesterol, high-sensitivity C-reactive protein, and apolipoprotein B, as well
      as other emerging targets, including LDL particle number and lipoprotein(a). In
      many high-risk patients, statin monotherapy is unlikely to achieve goals, and
      combination therapy with other agents is a safe, effective, and optimal
      therapeutic approach.

PMID- 19158582
TI  - Examining the challenges of recruiting women into a cardiac rehabilitation
      clinical trial.
AB  - PURPOSE: To examine the challenges of recruiting women for a 5-year cardiac
      rehabilitation randomized clinical trial; the aims of the study were to describe
      the range of recruitment sources, examine the myriad of factors contributing to
      ineligibility and nonparticipation of women during protocol screening, and
      discuss the challenges of enrolling women in the trial. METHODS: The Women's-Only
      Phase II Cardiac Rehabilitation program used an experimental design with 2
      treatment groups. Eligible participants included women who were (1) diagnosed
      with a myocardial infarction or stable angina or had undergone coronary
      revascularization within the last 12 months; (2) able to read, write, and speak
      English; and (3) older than 21 years. Responses to multiple recruitment
      strategies including automatic hospital referrals, physician office referrals,
      mass mailings, media advertisements, and community outreach are described.
      Reasons for ineligibility and nonparticipation in the trial are explored.
      RESULTS: Automatic hospital order was the largest source of referral (n = 1,367,
      81%) accounting for the highest enrollment rate of women (n = 184, 73%). The
      barriers to enrollment into the cardiac rehabilitation clinical trial included
      patient-oriented, provider-oriented, and programmatic factors. Of the referral
      sources, 52% were screened ineligible for provider-oriented reasons, 31% were
      ineligible due to patient-oriented factors, and 17.4% were linked to the study
      protocol. Study nonparticipation of those eligible (73.8%) was largely associated
      with patient-oriented factors (65.2%), with far less due to provider-related
      factors (4%) or study-related factors (3.4%). CONCLUSION: Standing hospital
      orders facilitated enrollment to the cardiac rehabilitation clinical trial, yet
      women failed to participate predominantly due to significant patient-oriented
      biopsychosocial barriers.

PMID- 19158584
TI  - Correlates of depression at baseline among African Americans enrolled in cardiac
      rehabilitation.
AB  - PURPOSE: To compare baseline psychosocial characteristics of African Americans
      entering phase 2 cardiac rehabilitation who have depression symptoms at or above
      threshold (Center for Epidemiological Studies Depression Scale [CES-D] score
      >or=16) with those who do not (CES-D score <16). METHODS: A nonrandom sample of
      112 men and women (n = 78 without depression, n = 34 with depression) was
      recruited through local phase 2 cardiac rehabilitation programs. Data were
      obtained by a structured interview and brief physical examination using several
      reliable and valid instruments. Chi-square tests, Kruskal-Wallis 2-sample tests,
      Spearman rank correlation coefficients, and logistic regression models were used
      for analyses. RESULTS: We found that 30% of the participants were above the
      depression symptom threshold. Demographic characteristics were not significantly
      different between individuals at or above threshold and those below threshold.
      However, depressed individuals above threshold were more likely to be
      dissatisfied with their neighborhoods (P = .01) and had lower optimism scores (P
      < .0001), higher stress scores (P < .0001), lower adaptive coping scores (P =
      .05), and higher problematic coping scores (P < .01) than their counterparts who
      were below threshold. In the logistic regression model, the odds of being above
      the depression symptom threshold increased with stress (P < .001) and decreased
      with optimism (P = .03); none of the other psychosocial characteristics had an
      independent effect on depression symptoms. CONCLUSIONS: At baseline, African
      Americans starting phase 2 cardiac rehabilitation with depression symptoms at or
      above threshold had more stress and fewer stress resilience factors. Assessing
      depression and stress resilience factors is important and may lead to more active
      participation in cardiac rehabilitation once enrolled, as well as optimal
      cardiovascular health outcomes.

PMID- 19158585
TI  - Hopelessness and its effect on cardiac rehabilitation exercise participation
      following hospitalization for acute coronary syndrome.
AB  - PURPOSE: Hopelessness has been associated with a higher risk of fatal and
      nonfatal coronary heart disease, yet very few studies have examined hopelessness
      after a cardiac event. This investigation examined hopelessness as an independent
      predictor of participation in a hospital-based cardiac rehabilitation exercise
      program. METHODS: A total of 207 patients with acute coronary syndrome were
      interviewed at 3 and 8 months after hospital discharge. Measures included 1
      factor of the Beck Hopelessness Scale, the Center for Epidemiological Studies
      Depression Scale, the Activity Status Index, the Charlson Comorbidity Index, a
      sociodemographic variables tool, and a cardiac rehabilitation exercise
      participation questionnaire. RESULTS: Random-effects logistic regression analysis
      revealed that hopelessness persisted over time and was an independent predictor
      of lower exercise participation. In contrast, depression showed no significant
      influence on exercise participation. CONCLUSIONS: Study findings suggest the
      importance of assessing hopelessness in patients with acute coronary syndrome and
      identifying approaches to exercise recommendations that directly address
      hopelessness. Interventions focused on the prevention and treatment of
      hopelessness symptoms may contribute to improved recovery of patient with acute
      coronary syndrome.

PMID- 19158586
TI  - Outcomes and adverse events among patients with implantable cardiac
      defibrillators in cardiac rehabilitation: a case-controlled study.
AB  - PURPOSE: This study aimed to assess the clinical outcomes and adverse events
      among patients with implantable cardiac defibrillators (ICDs) in cardiac
      rehabilitation programs. METHODS: Data were compared for 42 consecutive patients
      with ICDs and 42 control patients matched by age, gender, and left ventricular
      ejection fraction without ICDs and enrolled in the same program. RESULTS: The
      number of cardiac rehabilitation exercise sessions for each group was 828 and
      925, respectively. Only 1 patient experienced an ICD firing during exercise;
      there were no cardiac arrests and no deaths in either group. Compliance with
      cardiac rehabilitation was similar in both groups with most dropouts for
      nonmedical reasons and similar rates for cardiac-related reasons. Improvements in
      exercise capacity were similar between groups (30% in ICD patients and 37% in
      controls). CONCLUSIONS: Although larger studies are needed, these data suggest
      that supervised exercise training in patients with ICDs appears to be safe and
      effective.

PMID- 19158587
TI  - Noninvasive ventilation with continuous positive airway pressure acutely improves
      6-minute walk distance in chronic heart failure.
AB  - BACKGROUND: Noninvasive ventilation with continuous positive airway pressure
      (CPAP) has been used in patients with chronic heart failure (CHF), although its
      effect on exercise tolerance in these patients is unknown. The aim of this study
      was to determine the effects of CPAP on exercise tolerance in outpatients with
      CHF. METHODS: Following a double-blind, randomized, crossover, and placebo
      controlled protocol, 12 patients with CHF (8 male; 4 female; age 54 +/- 12 years;
      body mass index 27.3 +/- 1.8 kg/m2, New York Heart Association Class II, III)
      underwent CPAP via nasal mask for 30 minutes in a recumbent position. Mask
      pressure was 3 cm H2O for 10 minutes, followed by individual progression up to 4
      to 6 cm H2O, whereas placebo was fixed 0 to 1 cm H2O. A 6-minute walk test was
      performed after placebo and CPAP. RESULTS: Continuous positive airway pressure
      decreased the resting heart rate (pre: 80 +/- 17 bpm; post: 71 +/- 15 bpm; P =
      .001) and mean arterial pressure (pre: 103 +/- 14 mm Hg; post: 97 +/- 13 mm Hg; P
      = .008). During exercise test, CPAP increased the distance covered (CPAP: 538 +/-
      78 m; placebo: 479 +/- 83 m; P < .001) and the peak heart rate (CPAP: 98 +/- 17;
      placebo: 89 +/- 12 bpm; P = .049) but did not change the peak mean arterial
      pressure (P = .161). CONCLUSION: Noninvasive ventilation with CPAP increased
      exercise tolerance in patients with stable CHF. Future clinical trials should
      investigate whether this effect is associated with improved clinical outcome.

PMID- 19158588
TI  - The prevalence of posttraumatic stress disorder in patients undergoing pulmonary
      rehabilitation and changes in PTSD symptoms following rehabilitation.
AB  - PURPOSE: Posttraumatic stress disorder (PTSD) is a common serious condition,
      which, although treatable, is often undetected. We investigated the prevalence of
      PTSD in patients with chronic obstructive pulmonary disease (COPD) referred to
      pulmonary rehabilitation and the impact of rehabilitation on PTSD symptoms.
      METHODS: Patients with COPD attending pulmonary rehabilitation programs in South
      West England completed cross-sectional and longitudinal surveys. Outcome measures
      included the Posttraumatic Diagnostic Scale, Impact of Events scale, Incremental
      Shuttle Walking Test, Medical Outcomes Short Form 12, Hospital Anxiety and
      Depression scale (HADS), and Chronic Respiratory Questionnaire. Questionnaires
      were completed at face-to-face interviews with participants 1 week before
      commencing pulmonary rehabilitation and at the end of the program. RESULTS:
      Patients (N = 100), mean age 68 years, 65% men, served as subjects. Seventy-four
      participants reported traumatic experiences (37 related to lung disease) and 70
      completed the pulmonary rehabilitation program. Eight of 100 participants met
      diagnostic criteria for PTSD. Participants with PTSD reported worse health status
      than those without PTSD. After pulmonary rehabilitation, exercise capacity and
      quality of life scores improved significantly, but PTSD symptom severity did not
      change. CONCLUSIONS: PTSD was present in 8% of COPD patients referred for
      pulmonary rehabilitation. After rehabilitation, participants with PTSD improved
      more in respect to anxiety and disease-specific health status than those without
      PTSD. PTSD symptoms did not improve following rehabilitation, despite its
      positive effects on HADS scores, exercise, and health status in this cohort.

PMID- 19158589
TI  - Comparison of pedometer and activity diary for measurement of physical activity
      in chronic obstructive pulmonary disease.
AB  - PURPOSE: Precise, inexpensive tools for measuring physical activity levels are
      important for developing strategies to improve symptoms and enhance quality of
      life in chronic obstructive pulmonary disease (COPD). Self-report questionnaires
      and diaries have been used in many populations with variable results. The
      pedometer is widely recognized as a valid and reliable objective measurement
      tool, but it has not been well tested in COPD. This study aimed to determine the
      relationship between free-living physical activity recorded in a daily diary and
      that measured by using a pedometer in patients with COPD. METHODS: Participants
      with COPD (n = 80) recorded physical activity over 7 days. Cumulative pedometer
      readings and diary records of 4 activity categories for each 0.5 hour were
      compared. RESULTS: Participants (n = 76) with complete data sets were included in
      the analysis. The diary was more reliably completed. Mean pedometer reading per
      week was 23,129 (SD = 17,083) "step" counts (range, 1,725-66,454). Mean diary
      recorded standing and walking time per week was 98.9 (SD = 10.4) hours (range, 73
      119.5). The relationship between these measures was moderate and statistically
      significant (r = 0.37, P = .001). CONCLUSIONS: A daily diary record appears to
      offer more promise than the pedometer as a tool for measuring free-living
      physical activity in patients with COPD. Further research is required to assess
      the value of the 2 methods as discriminative, evaluative, and predictive tools in
      COPD populations.

PMID- 19158590
TI  - TBI in the military. Preface.

PMID- 19158591
TI  - The Veterans Health Administration's (VHA's) Polytrauma System of Care for mild
      traumatic brain injury: costs, benefits, and controversies.
AB  - The Veterans Health Administration's (VHA's) Polytrauma System of Care, developed
      in response to a new cohort of patients back from Iraq and Afghanistan, is
      described with particular focus on the assessment and treatment of mild traumatic
      brain injury (mild TBI). The development of systemwide TBI screening within the
      VHA has been an ambitious and historic undertaking. As with any population-wide
      screening tool, there are benefits and costs associated with it. The purpose of
      this article is to identify and discuss the strengths and weaknesses of the VHA's
      TBI clinical reminder and subsequent evaluation and treatment processes.
      Complicating factors such as increased media attention and other contextual
      factors are discussed.

PMID- 19158592
TI  - Traumatic brain injury screening: preliminary findings in a US Army Brigade
      Combat Team.
AB  - OBJECTIVES: The objective of this article is to report the proportion of soldiers
      in a Brigade Combat Team (BCT) with at least 1 clinician-confirmed deployment
      acquired traumatic brain injury (TBI) and to describe the nature of sequelae
      associated with such injuries. PARTICIPANTS: Members of an Army unit (n = 3973)
      that served in Iraq were screened for history of TBI. Those reporting an injury
      (n = 1292) were further evaluated regarding sequelae. Of the injuries suffered,
      907 were TBIs and 385 were other types of injury. The majority of TBIs sustained
      were mild. METHODS: Postdeployment, responses to the Warrior Administered
      Retrospective Casualty Assessment Tool (WARCAT) facilitated clinical interviews
      regarding injury history and associated somatic (ie, headache, dizziness,
      balance) and neuropsychiatric symptoms (ie, irritability, memory). Traumatic
      brain injury diagnosis was based on the American Congress of Rehabilitation
      Medicine mild TBI criteria, which requires an injury event followed by an
      alteration in consciousness. RESULTS: A total of 22.8% of soldiers in a BCT
      returning from Iraq had clinician-confirmed TBI. Those with TBI were
      significantly more likely to recall somatic and/or neuropsychiatric symptoms
      immediately postinjury and endorse symptoms at follow-up than were soldiers
      without a history of deployment-related TBI. A total of 33.4% of soldiers with
      TBI reported 3 or more symptoms immediately postinjury compared with 7.5% at
      postdeployment. For soldiers injured without TBI, rates of 3 or more symptoms
      postinjury and postdeployment were 2.9% and 2.3%, respectively. In those with
      TBI, headache and dizziness were most frequently reported postinjury, with
      irritability and memory problems persisting and presenting over time. CONCLUSION:
      Following deployment to Iraq, a clinician-confirmed TBI history was identified in
      22.8% of soldiers from a BCT. Those with TBI were significantly more likely to
      report postinjury and postdeployment somatic and/or neuropsychiatric symptoms
      than those without this injury history. Overall, symptom endorsement decreased
      over time.

PMID- 19158593
TI  - Performance on the Automated Neuropsychological Assessment Metrics in a
      nonclinical sample of soldiers screened for mild TBI after returning from Iraq
      and Afghanistan: a descriptive analysis.
AB  - PURPOSE: To characterize cognitive test performance in a sample of US Army
      soldiers who had served in Iraq and Afghanistan and were tested after returning
      to their home base. To determine whether if a self-reported history of deployment
      related traumatic brain injury (TBI), lifetime history of TBI, and the current
      postconcussive symptom status affected cognitive test performance. METHODS: A
      convenience sample of 956 soldiers was administered the Automated
      Neuropsychological Assessment Metrics (ANAM) test battery as well as
      questionnaires asking about deployment-related TBI, lifetime TBI history, and
      current TBI-related symptoms. RESULTS: Consistent with past mild TBI (MTBI)
      research, having a history of deployment-related MTBI up to 2 years prior to
      cognitive testing was not associated with poor ANAM performance after deployment.
      There also were no associations between poor ANAM performance and the number of
      lifetime TBIs, and injury severity and the number of problematic postconcussive
      symptoms. CONCLUSIONS: A history of self-reported MTBI or current postconcussive
      symptoms does not increase the risk of cognitive impairment in service members
      returning from Iraq and Afghanistan.

PMID- 19158594
TI  - Relationship between processing speed and executive functioning performance among
      OEF/OIF veterans: implications for postdeployment rehabilitation.
AB  - BACKGROUND: Comorbid mild traumatic brain injury (mTBI) with posttraumatic stress
      disorder (PTSD) is a common clinical presentation among troops returning from
      Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF). This study
      examined processing speed and executive functioning in a sample of OEF/OIF
      veterans who had sustained mTBI, a subset of whom also had comorbid PTSD.
      METHODS: Fifty-three OEF/OIF veterans with a history of mTBI completed Wechsler
      Adult Intelligence Scale-III Symbol Search and Digit Symbol-Coding subscales,
      Stroop Word, color and color-word trials, and Trail Making Test, Parts A and B as
      part of a comprehensive neuropsychological test battery. RESULTS: Excluding from
      analysis those who scored poorly on effort testing, multiple regression showed
      that measures of processing speed accounted for 43% of the variance in
      performance on the Trail Making Test, Part B and 50% of the variance in
      performance on the Stroop task. Significant differences in processing speed and
      executive functioning were found on the basis of presence of comorbid PTSD.
      Stroop Color (F = 9.27, df = 52, P < .004) and Stroop Color Word (F = 7.19, df =
      52, P < .01) scores differed significantly between the groups. Those having
      comorbid PTSD (+TBI/+PTSD) scored significantly poorer than the mTBI-only group
      (+TBI/-PTSD). Implications for treatment of the comorbid conditions are
      discussed.

PMID- 19158595
TI  - Traumatic brain injury associated with combat ocular trauma.
AB  - PURPOSE: To determine the impact of traumatic brain injury (TBI) on visual
      outcomes in combat ocular trauma (COT) and determine the association between TBI
      severity and types of ocular injuries. PARTICIPANTS: One hundred fifty-two US
      casualties sustained 207 globe/oculoplastic combat injuries. METHODS:
      Retrospective, hospital-based cross-sectional study of US service members injured
      during Operations Iraqi Freedom and Enduring Freedom were treated by the
      Ophthalmology Service at Walter Reed Army Medical Center and screened for TBI by
      the Defense and Veterans Brain Injury Center from August 2004 to October 2006.
      MAIN OUTCOME MEASURES: The main outcome measure was best-corrected visual acuity
      (BCVA). Secondary outcome measures included the severity and frequency of TBI
      with globe, oculoplastic, and/or neuro-ophthalmic injury. RESULTS: The frequency
      of COT with positive TBI screening was 101 of 152 cases (66%) in comparison with
      negative TBI screening, which was 51 of 152 (34%) cases. The Defense and Veterans
      Brain Injury Center found TBI with concomitant ocular trauma in 101 of 474 (21%)
      consecutive casualties. Explosive fragmentary munitions accounted for 79% of TBI
      associated COT. The median follow-up was 185 days. Traumatic brain injury
      severity did not correlate with worse final BCVA (Spearman coefficient, r =
      0.12). The odds that BCVA worse than 20/200 was present with TBI was not
      statistically significant (OR: 1.5; 95% CI, 0.9-2.6; P = .10). The presence of
      TBI in COT was not associated with worse visual outcome (Mann-Whitney U test, P =
      .10). Globe injuries were more common than oculoplastic or neuro-ophthalmic
      injury. Closed-globe injuries were more likely to have TBI than open-globe
      injuries (OR: 2.17; 95% CI, 1.12-4.21; P = .03). Traumatic brain injury severity
      associated with COT included mild TBI (31%), moderate TBI (30%), severe TBI
      (25%), and penetrating TBI (14%). Severe TBI is more frequently associated with
      COT. CONCLUSION: Traumatic brain injury occurs in two thirds of all COT and
      ocular trauma is a common finding in all TBI cases. Closed-globe injuries are at
      highest risk for TBI while TBI does not appear to lead to poorer visual outcomes.
      Every patient with COT needs TBI screening. Those service members who are
      screened TBI positive need a referral to a TBI rehabilitation specialist.

PMID- 19158596
TI  - The potential utility of driving simulators in the cognitive rehabilitation of
      combat-returnees with traumatic brain injury.
AB  - A large number of Operation Enduring Freedom/Operation Iraqi Freedom returnees
      are seeking DOD and VA rehabilitative care for war-related traumatic brain injury
      (TBI). This article reviews evidence on the utility of driving simulators as
      tools for assessment and training in TBI rehabilitation. Traditionally, cognitive
      rehabilitation has been shown to improve specific cognitive skills. However,
      there are few studies and only weak evidence to show that these gains transfer to
      everyday activities. Theoretically, modern driving simulators may be useful in
      cognitive rehabilitation because they can systematically present realistic and
      interesting tasks that approximate driving activities, while automatically
      monitoring performance. The use of simulation technology for patients with TBI
      provides cognitive stimulation in an ecologically compatible setting, without the
      risks associated with a corresponding real-world experience. The utility,
      limitations, and future directions for the use of driving simulator in the
      rehabilitation of patients with war-related TBI are discussed.

PMID- 19158597
TI  - Clinical, cognitive, and genetic predictors of change in job status following
      traumatic brain injury in a military population.
AB  - OBJECTIVE: Traumatic brain injury (TBI) is a risk associated with military duty,
      and residual effects from TBI may adversely affect a service member's ability to
      complete duties. It is, therefore, important to identify factors associated with
      a change in job status following TBI in an active military population. On the
      basis of previous research, we predicted that apolipoprotein E (APOE) genotype
      may be 1 factor. DESIGN: Cohort study of military personnel who sustained a mild
      to moderate TBI. SETTING: Military medical clinics. PATIENTS OR OTHER
      PARTICIPANTS: Fifty-two military participants were recruited through the Defense
      and Veterans Brain Injury Center, affiliated with Naval Medical Center San Diego
      and the Defense and Veterans Brain Injury Center Concussion Clinic located at the
      First Marine Division at Camp Pendleton. INTERVENTION(S): A multivariate
      statistical classification approach called optimal data analysis allowed for
      consideration of APOE genotype alongside cognitive, emotional, psychosocial, and
      physical functioning. MAIN OUTCOME MEASURE(S): APOE genotype, neuropsychological,
      psychosocial, and clinical outcomes. RESULTS: We identified a model of factors
      that was associated with a change in job status among military personnel who
      experienced a mild or moderate TBI. CONCLUSIONS: Factors associated with a change
      in job status are different when APOE genotype is considered. We conclude that
      APOE genotype may be an important genetic factor in recovery from mild to
      moderate head injury.

PMID- 19158598
TI  - Polymorphisms in genes modulating the dopamine system: do they inf luence outcome
      and response to medication after traumatic brain injury?

PMID- 19158599
TI  - Heterotopic ossification: pharmacologic options.

PMID- 19158600
TI  - Doing good: the pitfalls of beneficence.

PMID- 19158604
TI  - Cardiac natriuretic peptides gene expression and secretion in inflammation.
AB  - The genetic expression and secretion of the cardiac polypeptide hormones atrial
      natriuretic factor (ANF or ANP) and brain natriuretic peptide (BNP) have been
      studied mainly in the context of cardiac diseases associated with neuroendocrine
      and hemodynamic changes arising from cardiac dysfunction such as in chronic
      congestive heart failure. In this type of pathology, both ANF and BNP plasma
      levels change in an approximate coordinated fashion so that the use of these
      hormones as biomarkers of cardiac disease is, in principle, indistinctive.
      However, we reported that during an acute cardiac allograft rejection episode,
      BNP plasma levels can significantly increase in the absence of a similar increase
      in ANF plasma levels. We tested the hypothesis that these changes were related to
      cytokines and found that some pro-inflammatory cytokines, including TNFalpha and
      IL-1beta, selectively promote BNP synthesis and secretion in cultures of neonatal
      rat ventricular cardiocytes. This effect was found related to increased BNP
      promoter activity and sensitive to p38 mitogen-activated protein kinase
      inhibition.In order to determine in vivo if the selective up-regulation of BNP
      would be observed in inflammatory processes other than acute cardiac allograft
      rejection, we carried out investigation using the experimental autoimmune
      myocarditis rat model, which histologically resembles human giant cell
      myocarditis. It was found that this model is also accompanied by a specific
      increase in BNP-circulating levels although the cytokines involved seem to differ
      from those characterized earlier through in vitro studies.Recent studies in
      humans have found that in sepsis, plasma BNP levels increase in the absence of
      hemodynamic changes.In conclusion, BNP appears to be regulated uniquely in the
      setting of an inflammatory process. This sets it apart from ANF in terms of
      potential roles in the pathogenesis of disease and in its use as a biomarker of
      cardiac disease.

PMID- 19158605
TI  - Natriuretic peptides in chronic kidney disease and during renal replacement
      therapy: an update.
AB  - Natriuretic peptides play a major role in sodium and body volume homeostasis in
      patients with adequate kidney function. Circulating B-type natriuretic peptide
      (BNP) and its amino-terminal fragment NT-proBNP provide important information on
      cardiac dysfunction, hypervolemia, and risk for hospitalization or death even in
      patients with severe impairment of kidney function. NT-proBNP acts also as
      significant independent predictor of progression of chronic kidney disease (CKD).
      Differences in elimination and degradation as well as molecular weight and half
      life between BNP and NT-proBNP are responsible for different plasma levels,
      different membrane-dependent removal during hemodialysis, and different
      diagnostic and prognostic power to predict morbidity and mortality in patients at
      different stages of CKD and in those on hemodialysis or peritoneal dialysis.
      Serial estimations of natriuretic peptides will help in the identification of
      potential complications in CKD patients with or without renal replacement
      therapies and probably improve outcome of these patients.

PMID- 19158603
TI  - Designer natriuretic peptides.
AB  - Designer natriuretic peptides (NPs) are novel hybrid peptides that are engineered
      from the native NPs through addition, deletion, or substitution of amino acid(s)
      with a goal toward optimization of pharmacological actions while minimizing
      undesirable effects. In this article, selected peptides that were designed in our
      laboratory are reviewed, and future directions for research and development of
      designer NPs are discussed.

PMID- 19158607
TI  - Motorcycle safety: using your head.

PMID- 19158615
TI  - Visual screening for scoliosis.

PMID- 19158622
TI  - . . . About osteoporosis.

PMID- 19158627
TI  - Focusing on video surveillance to reduce falls.

PMID- 19158628
TI  - Coming to terms with cytomegalovirus.

PMID- 19158640
TI  - An upward trend in motorcycle crashes.
AB  - Motorcycle crashes are on the rise. Take a team approach to managing a patient
      with multiple traumatic injuries.

PMID- 19158642
TI  - Patient education series. Treating cough in children.

PMID- 19158643
TI  - Cholecystectomy: take a look at two options.
AB  - Open surgery or laparoscopy? Find out how to care for a patient who's undergoing
      either type of surgery.

PMID- 19158644
TI  - NEW DRUGS 09: part 1.

PMID- 19158646
TI  - Improving handoff communication.
AB  - By improving our process, we enhanced patient care and made handoff communication
      more effective.

PMID- 19158647
TI  - The case of the false alarm.
AB  - For a green nursing student just starting work in a hospital, even the most
      mundane sights and sounds can seem mysterious.

PMID- 19158648
TI  - Managing posttransplantation pain syndromes.

PMID- 19158650
TI  - Interpreting menstrual abnormalities.

PMID- 19158651
TI  - Perforated diverticulitis.

PMID- 19158652
TI  - Returning to work after stroke: a review.
AB  - This review focuses on the experiences and rehabilitation needs of working age,
      higher functioning stroke survivors in relation to their 'return to work'. It
      grew out of the poststroke experience of one of the authors and her realization
      of the inadequacy of services to facilitate return to work and optimal recovery
      from stroke. The authors' aim is to present a practice-oriented review that can
      provide information for future practice and research. Returning to work and
      sustaining employment are considered key aspects of rehabilitation and recovery
      by younger stroke survivors. From a psychosocial perspective, successful return
      to work can enhance recovery and life satisfaction by consolidating self-esteem,
      confidence and social identity. However, even higher functioning stroke survivors
      with minimal or no obvious physical disability may experience workplace
      challenges relating to their neurological condition. Appropriate rehabilitation
      would include specific preparation for return to work, education within the
      workplace to facilitate return to work, participation by the stroke survivor in
      all aspects of the management of their return to work, and an ongoing role for a
      stroke educator/workplace advocate. In conclusion, further research is required
      in this area to support stroke survivors in returning to and maintaining
      employment to achieve their poststroke potential. Thirteen recommendations
      arising from the existing literature and the lived experience of one of the
      authors are presented at the end of the review.

PMID- 19158653
TI  - A new atisane-type diterpene from the bark of the mangrove plant Excoecaria
      agallocha.
AB  - A new atisane-type diterpene, ent-16alpha-hydroxy-atisane-3,4-lactone (4) and
      three known diterpenes, ent-16alpha-hydroxy-atisane-3-one (1), ent-atisane
      3beta,16alpha-diol (2), ent-3,4-seco-16alpha-hydroxyatis- 4(19)-en -3-oic acid
      (3) were isolated from the bark of the mangrove plant Excoecaria agallocha. Their
      structures and relative stereochemistry were elucidated by means of extensive NMR
      and MS analysis. Compound 3 exhibited significant anti-microfouling activity
      against the adherence of Pseudomonas pseudoalcaligenes, with an EC(50) value of
      0.54+/-0.01 ppm.

PMID- 19158654
TI  - Multiscale modeling of dendrimers and their interactions with bilayers and
      polyelectrolytes.
AB  - Recent advances in molecular dynamics simulation methodologies and computational
      power have allowed accurate predictions of dendrimer size, shape, and
      interactions with bilayers and polyelectrolytes with modest computational effort.
      Atomistic and coarse-grained (CG) models show strong interactions of cationic
      dendrimers with lipid bilayers. The CG simulations with explicit lipid and water
      capture bilayer penetration and pore formation, showing that pore formation is
      enhanced at high dendrimer concentration, but suppressed at low temperature and
      high salt concentration, in agreement with experiments. Cationic linear polymers
      have also been simulated, but do not perforate membranes, evidently because by
      deforming into a pancake, the charges on a linear polymer achieve intimate
      contact with a single bilayer leaflet. The relatively rigid dendrimers, on the
      other hand, penetrate the bilayer, because only by interacting with both leaflets
      can they achieve a similar degree of contact between charged groups. Also, a
      "dendrimer-filled vesicle" structure for the dendrimer-membrane interaction is
      predicted by mesoscale thermodynamic simulations, in agreement with a picture
      derived from experimental observations. In simulations of complexes of dendrimer
      and polyelectrolyte, anionic linear chains wrap around the cationic dendrimer and
      penetrate inside it. Overall, these new results indicate that simulations can now
      provide predictions in excellent agreement with experimental observations, and
      provide atomic-scale insights into dendrimer structure and dynamics.

PMID- 19158656
TI  - Mechanochemical solvent-free and catalyst-free one-pot synthesis of pyrano[2,3
      d]pyrimidine-2,4(1H,3H)-diones with quantitative yields.
AB  - Solvent-free synthesis of pyrano[2,3-d]pyrimidine-2,4(1H,3H)-diones by ball
      milling and without any catalyst is described. This method provides several
      advantages such as being environmentally friendly, using a simple workup
      procedure, and affording high yields.

PMID- 19158655
TI  - Phenolics: occurrence and immunochemical detection in environment and food.
AB  - Phenolic compounds may be of natural or anthropogenic origin and be present in
      the environment as well as in food. They comprise a large and diverse group of
      compounds that may be either beneficial or harmful for consumers. In this review
      first a non-exhausting overview of interesting phenolics is given, in particular
      with regards to their presence in environment and food. For some of these
      compounds, beneficial, toxicological and/or optionally endocrine disrupting
      activities will be presented. Further, immunochemical detection and/or isolation
      methods developed will be discussed, including advantages and disadvantages
      thereof in comparison with conventional analytical methods such as HPLC, GC, MS.
      A short overview of new sensor-like methods will also be included for present and
      future application.

PMID- 19158657
TI  - Total antioxidant capacity of some commercial fruit juices: electrochemical and
      spectrophotometrical approaches.
AB  - The aim of this paper was to assess the total antioxidant capacity of some
      commercial fruit juices (namely citrus), spectrophotometrically and by the
      biamperometric method, using the redox couple DPPH. (2,2-diphenyl-1
      picrylhydrazyl)/DPPH (2,2-diphenyl-1-picrylhydrazine). Trolox was chosen as a
      standard antioxidant. In the case of the spectrophometric method, the absorbance
      decrease of the DPPH. solution was followed. For the biamperometric method, the
      influence of some parameters like the potential difference, DeltaE, DPPH.
      concentration, and Trolox concentration was investigated. The calibration graph
      obtained for Trolox presents linearity between 5 and 30 microM, (y=0.059 x +
      0.0564, where y represents the value of current intensity, expressed as microA
      and x the value of Trolox concentration, expressed as muM; r(2)=0.9944). The
      R.S.D. value for the biamperometric method was 1.29% (n=10, c=15 microM Trolox).
      In the case of the spectrophotometric method, the calibration graph obtained for
      Trolox presents linearity between 0.01 and 0.125 mM (y= -9.5789 x+1.4533, where y
      represents the value of absorbance and x, the value of Trolox concentration,
      expressed as mM; r(2)=0.9963). The R.S.D. value for the spectrophotometric method
      was 2.05%. Both methods were applied to total antioxidant activity determination
      in real samples (natural juices and soft drinks) and the results were in good
      agreement.

PMID- 19158658
TI  - 2-amido-3-(1H-indol-3-yl)-N-substituted-propanamides as a new class of falcipain
      2 inhibitors. 1. Design, synthesis, biological evaluation and binding model
      studies.
AB  - The Plasmodium falciparum cysteine protease falcipain-2 (FP-2) is an important
      cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum
      trophozoites. The discovery of new FP-2 inhibitors is now a hot topic in the
      search for potential malaria treatments. In this study, a series of novel small
      molecule FP-2 inhibitors have been designed and synthesized based on three
      regional optimizations of the lead (R)-2-phenoxycarboxamido-3-(1H-indol-3-yl)-N
      benzylpropanamide(1), which was identified using structure-based virtual
      screening in conjunction with surface plasmon resonance (SPR)-based binding
      assays. Four compounds--1, 2b, 2k and 2l--showed moderate FP-2 inhibition
      activity, with IC(50) values of 10.0-39.4 microM, and the inhibitory activity of
      compound 2k was approximately 3-fold better than that of the prototype compound 1
      and may prove useful for the development of micromolar level FP-2 inhibitors.
      Preliminary SAR data was obtained, while molecular modeling revealed that
      introduction of H-bond donor or/and acceptor atoms to the phenyl ring moiety in
      the C region would be likely to produce some additional H-bond interactions,
      which should consequently enhance molecular bioactivity.

PMID- 19158659
TI  - Innovative approaches to the rehabilitation of upper extremity hemiparesis using
      virtual environments.
AB  - AIM: Upper-extremity interventions for hemiparesis are a challenging aspect of
      stroke rehabilitation. Purpose of this paper is to report the feasibility of
      using virtual environments (VEs) in combination with robotics to assist recovery
      of hand-arm function and to present preliminary data demonstrating the potential
      of using sensory manipulations in VE to drive activation in targeted neural
      regions. METHODS: We trained 8 subjects for 8 three hour sessions using a library
      of complex VE's integrated with robots, comparing training arm and hand
      separately to training arm and hand together. Instrumented gloves and hand
      exoskeleton were used for hand tracking and haptic effects. Haptic Master robotic
      arm was used for arm tracking and generating three-dimensional haptic VEs. To
      investigate the use of manipulations in VE to drive neural activations, we
      created a "virtual mirror" that subjects used while performing a unimanual task.
      Cortical activation was measured with functional MRI (fMRI) and transcranial
      magnetic stimulation. RESULTS: Both groups showed improvement in kinematics and
      measures of real-world function. The group trained using their arm and hand
      together showed greater improvement. In a stroke subject, fMRI data suggested
      virtual mirror feedback could activate the sensorimotor cortex contralateral to
      the reflected hand (ipsilateral to the moving hand) thus recruiting the lesioned
      hemisphere. CONCLUSION: Gaming simulations interfaced with robotic devices
      provide a training medium that can modify movement patterns. In addition to
      showing that our VE therapies can optimize behavioral performance, we show
      preliminary evidence to support the potential of using specific sensory
      manipulations to selectively recruit targeted neural circuits.

PMID- 19158660
TI  - Histone methylation sets the stage for meiotic DNA breaks.
AB  - Covalent post-translational modifications of histones have important functions in
      transcription, replication, repair, and other aspects of eukaryotic chromosome
      dynamics. Trimethylation of lysine-4 on histone H3 is enriched at actively
      transcribed loci in many organisms. The impact of this histone modification on
      transcription has been extensively studied, but less is known about its effects
      on other chromosomal processes. An intriguing new study in this issue of EMBO
      Journal demonstrates that H3 lysine-4 trimethylation is critical in budding yeast
      for formation of the programmed DNA double-strand breaks that initiate homologous
      recombination during meiosis. These findings have important implications for
      elucidating the previously recognized but little understood connections between
      meiotic break formation and transcriptional promoters in this organism.

PMID- 19158661
TI  - Circadian clocks can take a few transcriptional knocks.
AB  - A thought-provoking study in this issue of The EMBO Journal shows that the
      circadian clock in mouse fibroblasts is surprisingly insensitive to the
      inhibition of total cellular mRNA production. The authors go on to show
      intriguing parallels between compensation of period to changes in temperature and
      global transcription rate.

PMID- 19158662
TI  - A protein complex that regulates PtdIns(3,5)P2 levels.
AB  - Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) is needed for retrograde
      membrane trafficking from lysosomal and late endosomal compartments and its
      synthesis is tightly regulated. But how cells regulate PtdIns(3,5)P2 synthesis-
      for example, in response to hyperosmotic shock--remains unexplained. A paper from
      the Weisman group gives the most complete picture so far of a multiprotein
      complex that controls PtdIns(3,5)P2 synthesis and explains how a VAC14 mutation
      functionally impairs the scaffold protein at the heart of the complex and causes
      a neurodegenerative condition in mice.

PMID- 19158663
TI  - Oxygen-dependent binding of Nro1 to the prolyl hydroxylase Ofd1 regulates SREBP
      degradation in yeast.
AB  - Sre1, the fission yeast sterol regulatory element-binding protein, is an ER
      membrane-bound transcription factor that controls adaptation to low oxygen
      growth. Under low oxygen, Sre1 is proteolytically cleaved and the N-terminal
      transcription factor domain (Sre1N) is released from the membrane and enters the
      nucleus to activate hypoxic gene expression. Ofd1, a prolyl 4-hydroxylase-like 2
      oxoglutarate dioxygenase, controls the oxygen-dependent stability of Sre1N. In
      the presence of oxygen, Ofd1 accelerates the degradation of Sre1N, but under low
      oxygen Ofd1 is inhibited and Sre1N accumulates. To identify the regulators of
      Sre1N, we performed a plasmid-based screen for genes that increased Sre1N
      transcriptional activity. Here, we identify Nro1 (SPCC4B3.07) as a positive
      regulator of Sre1N stability and a direct inhibitor of Ofd1. In the absence of
      oxygen, Nro1 binds to the Ofd1 C-terminal degradation domain and inhibits Sre1N
      degradation. In the presence of oxygen, Nro1 binding to Ofd1 is disrupted,
      leading to rapid degradation of Sre1N. We conclude that the Ofd1 dioxygenase
      domain functions as an oxygen sensor that regulates binding of Nro1 to Ofd1 to
      control oxygen-dependent Sre1N stability.

PMID- 19158665
TI  - Perspectives on early communication of drug risks to the public.

PMID- 19158664
TI  - Smc5/6 maintains stalled replication forks in a recombination-competent
      conformation.
AB  - The Smc5/6 structural maintenance of chromosomes complex is required for
      efficient homologous recombination (HR). Defects in Smc5/6 result in chromosome
      mis-segregation and fragmentation. By characterising two Schizosaccharomyces
      pombe smc6 mutants, we define two separate functions for Smc5/6 in HR. The first
      represents the previously described defect in processing recombination-dependent
      DNA intermediates when replication forks collapse, which leads to increased rDNA
      recombination. The second novel function defines Smc5/6 as a positive regulator
      of recombination in the rDNA and correlates mechanistically with a requirement to
      load RPA and Rad52 onto chromatin genome-wide when replication forks are stably
      stalled by nucleotide depletion. Rad52 is required for all HR repair, but Rad52
      loading in response to replication fork stalling is unexpected and does not
      correlate with damage-induced foci. We propose that Smc5/6 is required to
      maintain stalled forks in a stable recombination-competent conformation primed
      for replication restart.

PMID- 19158666
TI  - Translational toxicology and the work of the predictive safety testing
      consortium.

PMID- 19158667
TI  - Metabotropic glutamate receptor 7 modulates the rewarding effects of cocaine in
      rats: involvement of a ventral pallidal GABAergic mechanism.
AB  - The metabotropic glutamate receptor 7 (mGluR7) has received much attention as a
      potential target for the treatment of epilepsy, major depression, and anxiety. In
      this study, we investigated the possible involvement of mGluR7 in cocaine reward
      in animal models of drug addiction. Pretreatment with the selective mGluR7
      allosteric agonist N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082;
      1-20 mg/kg, i.p.) dose-dependently inhibited cocaine-induced enhancement of
      electrical brain-stimulation reward and intravenous cocaine self-administration
      under both fixed-ratio and progressive-ratio reinforcement conditions, but failed
      to alter either basal or cocaine-enhanced locomotion or oral sucrose self
      administration, suggesting a specific inhibition of cocaine reward.
      Microinjections of AMN082 (1-5 microg/microl per side) into the nucleus accumbens
      (NAc) or ventral pallidum (VP), but not dorsal striatum, also inhibited cocaine
      self-administration in a dose-dependent manner. Intra-NAc or intra-VP co
      administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5
      c]pyridin-4(5H)-one (MMPIP, 5 microg/microl per side), a selective mGluR7
      allosteric antagonist, significantly blocked AMN082's action, suggesting an
      effect mediated by mGluR7 in these brain regions. In vivo microdialysis
      demonstrated that cocaine (10 mg/kg, i.p.) priming significantly elevated
      extracellular DA in the NAc or VP, while decreasing extracellular GABA in VP (but
      not in NAc). AMN082 pretreatment selectively blocked cocaine-induced changes in
      extracellular GABA, but not in DA, in both naive rats and cocaine self
      administration rats. These data suggest: (1) mGluR7 is critically involved in
      cocaine's acute reinforcement; (2) GABA-, but not DA-, dependent mechanisms in
      the ventral striatopallidal pathway appear to underlie AMN082's actions; and (3)
      AMN082 or other mGluR7-selective agonists may be useful in the treatment of
      cocaine addiction.

PMID- 19158668
TI  - Histone H3 phosphorylation is under the opposite tonic control of dopamine D2 and
      adenosine A2A receptors in striatopallidal neurons.
AB  - The antipsychotic agent haloperidol regulates gene transcription in striatal
      medium spiny neurons (MSNs) by blocking dopamine D2 receptors (D2Rs). We examined
      the mechanisms by which haloperidol increases the phosphorylation of histone H3,
      a key step in the nucleosomal response. Using bacterial artificial chromosome
      (BAC)-transgenic mice that express EGFP under the control of the promoter of the
      dopamine D1 receptor (D1R) or the D2R, we found that haloperidol induced a rapid
      and sustained increase in the phosphorylation of histone H3 in the
      striatopallidal MSNs of the dorsal striatum, with no change in its acetylation.
      This effect was mimicked by raclopride, a selective D2R antagonist, and prevented
      by the blockade of adenosine A2A receptors (A2ARs), or genetic attenuation of the
      A2AR-associated G protein, Galpha(olf). Mutation of the cAMP-dependent
      phosphorylation site (Thr34) of the 32-kDa dopamine and cAMP-regulated
      phosphoprotein (DARPP-32) decreased the haloperidol-induced H3 phosphorylation,
      supporting the role of cAMP in H3 phosphorylation. Haloperidol also induced
      extracellular signal-regulated kinase (ERK) phosphorylation in striatopallidal
      MSNs, but this effect was not implicated in H3 phosphorylation. The levels of
      mitogen- and stress-activated kinase 1 (MSK1), which has been reported to mediate
      ERK-induced H3 phosphorylation, were lower in striatopallidal than in
      striatonigral MSNs. Moreover, haloperidol-induced H3 phosphorylation was
      unaltered in MSK1-knockout mice. These data indicate that, in striatopallidal
      MSNs, H3 phosphorylation is controlled by the opposing actions of D2Rs and A2ARs.
      Thus, blockade of D2Rs promotes histone H3 phosphorylation through the A2AR
      mediated activation of Galpha(olf) and inhibition of protein phosphatase-1 (PP-1)
      through the PKA-dependent phosphorylation of DARPP-32.

PMID- 19158670
TI  - Pro-cognitive and antipsychotic efficacy of the alpha7 nicotinic partial agonist
      SSR180711 in pharmacological and neurodevelopmental latent inhibition models of
      schizophrenia.
AB  - Schizophrenia symptoms can be segregated into positive, negative and cognitive,
      which exhibit differential sensitivity to drug treatments. Accumulating evidence
      points to efficacy of alpha7 nicotinic receptor (nAChR) agonists for cognitive
      deficits in schizophrenia but their activity against positive symptoms is thought
      to be minimal. The present study examined potential pro-cognitive and
      antipsychotic activity of the novel selective alpha7 nAChR partial agonist
      SSR180711 using the latent inhibition (LI) model. LI is the reduced efficacy of a
      previously non-reinforced stimulus to gain behavioral control when paired with
      reinforcement, compared with a novel stimulus. Here, no-drug controls displayed
      LI if non-reinforced pre-exposure to a tone was followed by weak but not strong
      conditioning (2 vs 5 tone-shock pairings). MK801 (0.05 mg/kg, i.p.) -treated rats
      as well as rats neonatally treated with nitric oxide synthase inhibitor L-NoArg
      (10 mg/kg, s.c.) on postnatal days 4-5, persisted in displaying LI with strong
      conditioning, whereas amphetamine (1 mg/kg) -treated rats failed to show LI with
      weak conditioning. SSR180711 (0.3, 1, 3 mg/kg, i.p.) was able to alleviate
      abnormally persistent LI produced by acute MK801 and neonatal L-NoArg; these
      models are believed to model cognitive aspects of schizophrenia and activity here
      was consistent with previous findings with alpha7-nAChR agonists. In addition,
      unexpectedly, SSR180711 (1, 3 mg/kg, i.p.) potentiated LI with strong
      conditioning in no-drug controls and reversed amphetamine-induced LI disruption,
      two effects considered predictive of activity against positive symptoms of
      schizophrenia. These findings suggest that SSR180711 may be beneficial not only
      for the treatment of cognitive symptoms in schizophrenia, as reported multiple
      times previously, but also positive symptoms.

PMID- 19158669
TI  - PKCepsilon regulates behavioral sensitivity, binding and tolerance to the CB1
      receptor agonist WIN55,212-2.
AB  - The cannabinoid CB1 receptor (CB1) is one of the most abundant G protein-coupled
      receptors in the brain, but little is known about the mechanisms that modulate
      CB1 receptor signaling. Here, we show that inhibition or null mutation of the
      epsilon isozyme of protein kinase C (PKCepsilon) selectively enhances behavioral
      responses to the CB1 agonist WIN55,212-2 in mice, but not to the structurally
      unrelated CB1 agonist CP55,940. Binding affinity for [(3)H] WIN55,212-2 was
      increased in brain membranes from PKCepsilon(-/-) mice compared with
      PKCepsilon(+/+) mice. There was no difference in binding of the inverse agonist
      [(3)H] SR141716A. In addition, repeated administration of WIN55,212-2 produced
      greater analgesic and thermal tolerance in PKCvarepsilon(-/-) mice compared with
      PKCepsilon(+/+)mice. These results indicate that PKCvarepsilon selectively
      regulates behavioral sensitivity, CB1 receptor binding and tolerance to WIN55,212
      2.

PMID- 19158672
TI  - Office and out-of-office heart rate and the development of metabolic disorders.

PMID- 19158673
TI  - The emergence of "adult" diseases during childhood: impact of a diabetic
      pregnancy.

PMID- 19158674
TI  - A high-mobility electron-transporting polymer for printed transistors.
AB  - Printed electronics is a revolutionary technology aimed at unconventional
      electronic device manufacture on plastic foils, and will probably rely on
      polymeric semiconductors for organic thin-film transistor (OTFT) fabrication. In
      addition to having excellent charge-transport characteristics in ambient
      conditions, such materials must meet other key requirements, such as chemical
      stability, large solubility in common solvents, and inexpensive solution and/or
      low-temperature processing. Furthermore, compatibility of both p-channel (hole
      transporting) and n-channel (electron-transporting) semiconductors with a single
      combination of gate dielectric and contact materials is highly desirable to
      enable powerful complementary circuit technologies, where p- and n-channel OTFTs
      operate in concert. Polymeric complementary circuits operating in ambient
      conditions are currently difficult to realize: although excellent p-channel
      polymers are widely available, the achievement of high-performance n-channel
      polymers is more challenging. Here we report a highly soluble ( approximately 60
      g l(-1)) and printable n-channel polymer exhibiting unprecedented OTFT
      characteristics (electron mobilities up to approximately 0.45-0.85 cm(2) V(-1) s(
      1)) under ambient conditions in combination with Au contacts and various
      polymeric dielectrics. Several top-gate OTFTs on plastic substrates were
      fabricated with the semiconductor-dielectric layers deposited by spin-coating as
      well as by gravure, flexographic and inkjet printing, demonstrating great
      processing versatility. Finally, all-printed polymeric complementary inverters
      (with gain 25-65) have been demonstrated.

PMID- 19158676
TI  - AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA.
AB  - Host- and pathogen-associated cytoplasmic double-stranded DNA triggers the
      activation of a NALP3 (also known as cryopyrin and NLRP3)-independent
      inflammasome, which activates caspase-1 leading to maturation of pro-interleukin
      1beta and inflammation. The nature of the cytoplasmic-DNA-sensing inflammasome is
      currently unknown. Here we show that AIM2 (absent in melanoma 2), an interferon
      inducible HIN-200 family member that contains an amino-terminal pyrin domain and
      a carboxy-terminal oligonucleotide/oligosaccharide-binding domain, senses
      cytoplasmic DNA by means of its oligonucleotide/oligosaccharide-binding domain
      and interacts with ASC (apoptosis-associated speck-like protein containing a
      CARD) through its pyrin domain to activate caspase-1. The interaction of AIM2
      with ASC also leads to the formation of the ASC pyroptosome, which induces
      pyroptotic cell death in cells containing caspase-1. Knockdown of AIM2 by short
      interfering RNA reduced inflammasome/pyroptosome activation by cytoplasmic DNA in
      human and mouse macrophages, whereas stable expression of AIM2 in the non
      responsive human embryonic kidney 293T cell line conferred responsiveness to
      cytoplasmic DNA. Our results show that cytoplasmic DNA triggers formation of the
      AIM2 inflammasome by inducing AIM2 oligomerization. This study identifies AIM2 as
      an important inflammasome component that senses potentially dangerous cytoplasmic
      DNA, leading to activation of the ASC pyroptosome and caspase-1.

PMID- 19158675
TI  - AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome
      with ASC.
AB  - The innate immune system senses nucleic acids by germline-encoded pattern
      recognition receptors. RNA is sensed by Toll-like receptor members TLR3, TLR7 and
      TLR8, or by the RNA helicases RIG-I (also known as DDX58) and MDA-5 (IFIH1).
      Little is known about sensors for cytoplasmic DNA that trigger antiviral and/or
      inflammatory responses. The best characterized of these responses involves
      activation of the TANK-binding kinase (TBK1)-interferon regulatory factor 3
      (IRF3) signalling axis to trigger transcriptional induction of type I interferon
      genes. A second, less well-defined pathway leads to the activation of an
      'inflammasome' that, via caspase-1, controls the catalytic cleavage of the pro
      forms of the cytokines IL1beta and IL18 (refs 6, 7). Using mouse and human cells,
      here we identify the PYHIN (pyrin and HIN domain-containing protein) family
      member absent in melanoma 2 (AIM2) as a receptor for cytosolic DNA, which
      regulates caspase-1. The HIN200 domain of AIM2 binds to DNA, whereas the pyrin
      domain (but not that of the other PYHIN family members) associates with the
      adaptor molecule ASC (apoptosis-associated speck-like protein containing a
      caspase activation and recruitment domain) to activate both NF-kappaB and caspase
      1. Knockdown of Aim2 abrogates caspase-1 activation in response to cytoplasmic
      double-stranded DNA and the double-stranded DNA vaccinia virus. Collectively,
      these observations identify AIM2 as a new receptor for cytoplasmic DNA, which
      forms an inflammasome with the ligand and ASC to activate caspase-1.

PMID- 19158677
TI  - A micro-architecture for binocular disparity and ocular dominance in visual
      cortex.
AB  - In invertebrate predators such as the praying mantis and vertebrate predators
      such as wild cats the ability to detect small differences in inter-ocular retinal
      disparities is a critical means for accurately determining the depth of moving
      objects such as prey. In mammals, the first neurons along the visual pathway that
      encode binocular disparities are found in the visual cortex. However, a precise
      functional architecture for binocular disparity has never been demonstrated in
      any species, and coarse maps for disparity have been found in only one primate
      species. Moreover, the dominant approach for assaying the developmental
      plasticity of binocular cortical neurons used monocular tests of ocular dominance
      to infer binocular function. The few studies that examined the relationship
      between ocular dominance and binocular disparity of individual cells used single
      unit recordings and have provided conflicting results regarding whether ocular
      dominance can predict the selectivity or sensitivity to binocular disparity. We
      used two-photon calcium imaging to sample the response to monocular and binocular
      visual stimuli from nearly every adjacent neuron in a small region of the cat
      visual cortex, area 18. Here we show that local circuits for ocular dominance
      always have smooth and graded transitions from one apparently monocular
      functional domain to an adjacent binocular region. Most unexpectedly, we
      discovered a new map in the cat visual cortex that had a precise functional micro
      architecture for binocular disparity selectivity. At the level of single cells,
      ocular dominance was unrelated to binocular disparity selectivity or sensitivity.
      When the local maps for ocular dominance and binocular disparity both had
      measurable gradients at a given cortical site, the two gradient directions were
      orthogonal to each other. Together, these results indicate that, from the
      perspective of the spiking activity of individual neurons, ocular dominance
      cannot predict binocular disparity tuning. However, the precise local arrangement
      of ocular dominance and binocular disparity maps provide new clues regarding how
      monocular and binocular depth cues may be combined and decoded.

PMID- 19158680
TI  - Abstracts of the Annual Meeting of the United States and Canadian Academy of
      Pathology. March 7-13, 2009. Boston, Massachusetts, USA.

PMID- 19158678
TI  - Cdc14 inhibits transcription by RNA polymerase I during anaphase.
AB  - Chromosome condensation and the global repression of gene transcription are
      features of mitosis in most eukaryotes. The logic behind this phenomenon is that
      chromosome condensation prevents the activity of RNA polymerases. In budding
      yeast, however, transcription was proposed to be continuous during mitosis. Here
      we show that Cdc14, a protein phosphatase required for nucleolar segregation and
      mitotic exit, inhibits transcription of yeast ribosomal genes (rDNA) during
      anaphase. The phosphatase activity of Cdc14 is required for RNA polymerase I (Pol
      I) inhibition in vitro and in vivo. Moreover Cdc14-dependent inhibition involves
      nucleolar exclusion of Pol I subunits. We demonstrate that transcription
      inhibition is necessary for complete chromosome disjunction, because ribosomal
      RNA (rRNA) transcripts block condensin binding to rDNA, and show that bypassing
      the role of Cdc14 in nucleolar segregation requires in vivo degradation of
      nascent transcripts. Our results show that transcription interferes with
      chromosome condensation, not the reverse. We conclude that budding yeast, like
      most eukaryotes, inhibit Pol I transcription before segregation as a prerequisite
      for chromosome condensation and faithful genome separation.

PMID- 19158679
TI  - An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA
      sensor for the inflammasome.
AB  - Cytoplasmic DNA triggers activation of the innate immune system. Although
      'downstream' signaling components have been characterized, the DNA-sensing
      components remain elusive. Here we present a systematic proteomics screen for
      proteins that associate with DNA, 'crossed' to a screen for transcripts induced
      by interferon-beta, which identified AIM2 as a candidate cytoplasmic DNA sensor.
      AIM2 showed specificity for double-stranded DNA. It also recruited the
      inflammasome adaptor ASC and localized to ASC 'speckles'. A decrease in AIM2
      expression produced by RNA-mediated interference impaired DNA-induced maturation
      of interleukin 1beta in THP-1 human monocytic cells, which indicated that
      endogenous AIM2 is required for DNA recognition. Reconstitution of unresponsive
      HEK293 cells with AIM2, ASC, caspase-1 and interleukin 1beta showed that AIM2 was
      sufficient for inflammasome activation. Our data suggest that AIM2 is a
      cytoplasmic DNA sensor for the inflammasome.

PMID- 19158707
TI  - Abstracts of the Annual Meeting of the United States and Canadian Academy of
      Pathology. Boston, Massachusetts, USA. March 7-13, 2009.

PMID- 19158737
TI  - Dismal no more.

PMID- 19158738
TI  - China's wind-power potential.

PMID- 19158739
TI  - Choosing a world.

PMID- 19158746
TI  - Journal club. A cell biologist looks at the risk and promise of a new insight
      into stem cells and cancer.

PMID- 19158752
TI  - Not so sunny after all.

PMID- 19158751
TI  - Translational research in Berlin hits a roadblock.

PMID- 19158753
TI  - Ebola outbreak has experts rooting for answers.

PMID- 19158756
TI  - Which moon to shoot for?

PMID- 19158754
TI  - Cash boost for US science.

PMID- 19158757
TI  - A fly by any other name.

PMID- 19158758
TI  - No bull: genes for better milk.

PMID- 19158765
TI  - Renewable energy: Beijing's windy bet.

PMID- 19158766
TI  - Social networking: Crisis communication.

PMID- 19158767
TI  - Culture clash in Chinese university: a response.

PMID- 19158768
TI  - Lindauer's genius showed evolution in a simple experiment.

PMID- 19158769
TI  - Ecologists should join astronomers to oppose light pollution.

PMID- 19158770
TI  - When winning a Nobel Prize seems to run in the family.

PMID- 19158771
TI  - Scientists stand by decision to join Mbeki's AIDS panel.

PMID- 19158772
TI  - Being human: kinship: race relations.

PMID- 19158777
TI  - Neuroscience: Pre-emptive blood flow.

PMID- 19158778
TI  - Astrophysics: Galaxies in from the cold.

PMID- 19158779
TI  - Structural biology: actin in a twist.

PMID- 19158781
TI  - Climate change: Shifts in season.

PMID- 19158782
TI  - Molecular biology: Concealed enzyme coordination.

PMID- 19158783
TI  - Obituary: Daniel Carleton Gajdusek (1923-2008).

PMID- 19158784
TI  - RNA silencing.

PMID- 19158785
TI  - On the road to reading the RNA-interference code.
AB  - The finding that sequence-specific gene silencing occurs in response to the
      presence of double-stranded RNAs has had an enormous impact on biology,
      uncovering an unsuspected level of regulation of gene expression. This process,
      known as RNA interference (RNAi) or RNA silencing, involves small non-coding
      RNAs, which associate with nuclease-containing regulatory complexes and then pair
      with complementary messenger RNA targets, thereby preventing the expression of
      these mRNAs. Remarkable progress has been made towards understanding the
      underlying mechanisms of RNAi, raising the prospect of deciphering the 'RNAi
      code' that, like transcription factors, allows the fine-tuning and networking of
      complex suites of gene activity, thereby specifying cellular physiology and
      development.

PMID- 19158786
TI  - A three-dimensional view of the molecular machinery of RNA interference.
AB  - In eukaryotes, small non-coding RNAs regulate gene expression, helping to control
      cellular metabolism, growth and differentiation, to maintain genome integrity,
      and to combat viruses and mobile genetic elements. These pathways involve two
      specialized ribonucleases that control the production and function of small
      regulatory RNAs. The enzyme Dicer cleaves double-stranded RNA precursors,
      generating short interfering RNAs and microRNAs in the cytoplasm. These small
      RNAs are transferred to Argonaute proteins, which guide the sequence-specific
      silencing of messenger RNAs that contain complementary sequences by either
      enzymatically cleaving the mRNA or repressing its translation. The molecular
      structures of Dicer and the Argonaute proteins, free and bound to small RNAs,
      have offered exciting insights into the molecular mechanisms that are central to
      RNA silencing pathways.

PMID- 19158787
TI  - Small RNAs in transcriptional gene silencing and genome defence.
AB  - Small RNA molecules of about 20-30 nucleotides have emerged as powerful
      regulators of gene expression and genome stability. Studies in fission yeast and
      multicellular organisms suggest that effector complexes, directed by small RNAs,
      target nascent chromatin-bound non-coding RNAs and recruit chromatin-modifying
      complexes. Interactions between small RNAs and nascent non-coding transcripts
      thus reveal a new mechanism for targeting chromatin-modifying complexes to
      specific chromosome regions and suggest possibilities for how the resultant
      chromatin states may be inherited during the process of chromosome duplication.

PMID- 19158788
TI  - Viral and cellular messenger RNA targets of viral microRNAs.
AB  - Given the propensity of viruses to co-opt cellular pathways and activities for
      their benefit, it is perhaps not surprising that several viruses have now been
      shown to reshape the cellular environment by reprogramming the host's RNA
      interference machinery. In particular, microRNAs are produced by the various
      members of the herpesvirus family during both the latent stage of the viral life
      cycle and the lytic (or productive) stage. Emerging data suggest that viral
      microRNAs are particularly important for regulating the transition from latent to
      lytic replication and for attenuating antiviral immune responses.

PMID- 19158789
TI  - The promises and pitfalls of RNA-interference-based therapeutics.
AB  - The discovery that gene expression can be controlled by the Watson-Crick base
      pairing of small RNAs with messenger RNAs containing complementary sequence - a
      process known as RNA interference - has markedly advanced our understanding of
      eukaryotic gene regulation and function. The ability of short RNA sequences to
      modulate gene expression has provided a powerful tool with which to study gene
      function and is set to revolutionize the treatment of disease. Remarkably,
      despite being just one decade from its discovery, the phenomenon is already being
      used therapeutically in human clinical trials, and biotechnology companies that
      focus on RNA-interference-based therapeutics are already publicly traded.

PMID- 19158790
TI  - Changes in the phase of the annual cycle of surface temperature.
AB  - The annual cycle in the Earth's surface temperature is extremely large-comparable
      in magnitude to the glacial-interglacial cycles over most of the planet. Trends
      in the phase and the amplitude of the annual cycle have been observed, but the
      causes and significance of these changes remain poorly understood-in part because
      we lack an understanding of the natural variability. Here we show that the phase
      of the annual cycle of surface temperature over extratropical land shifted
      towards earlier seasons by 1.7 days between 1954 and 2007; this change is highly
      anomalous with respect to earlier variations, which we interpret as being
      indicative of the natural range. Significant changes in the amplitude of the
      annual cycle are also observed between 1954 and 2007. These shifts in the annual
      cycles appear to be related, in part, to changes in the northern annular mode of
      climate variability, although the land phase shift is significantly larger than
      that predicted by trends in the northern annular mode alone. Few of the climate
      models presented by the Intergovernmental Panel on Climate Change reproduce the
      observed decrease in amplitude and none reproduce the shift towards earlier
      seasons.

PMID- 19158791
TI  - The nature of the globular- to fibrous-actin transition.
AB  - Actin plays crucial parts in cell motility through a dynamic process driven by
      polymerization and depolymerization, that is, the globular (G) to fibrous (F)
      actin transition. Although our knowledge about the actin-based cellular functions
      and the molecules that regulate the G- to F-actin transition is growing, the
      structural aspects of the transition remain enigmatic. We created a model of F
      actin using X-ray fibre diffraction intensities obtained from well oriented sols
      of rabbit skeletal muscle F-actin to 3.3 A in the radial direction and 5.6 A
      along the equator. Here we show that the G- to F-actin conformational transition
      is a simple relative rotation of the two major domains by about 20 degrees. As a
      result of the domain rotation, the actin molecule in the filament is flat. The
      flat form is essential for the formation of stable, helical F-actin. Our F-actin
      structure model provides the basis for understanding actin polymerization as well
      as its molecular interactions with actin-binding proteins.

PMID- 19158792
TI  - Cold streams in early massive hot haloes as the main mode of galaxy formation.
AB  - Massive galaxies in the young Universe, ten billion years ago, formed stars at
      surprising intensities. Although this is commonly attributed to violent mergers,
      the properties of many of these galaxies are incompatible with such events,
      showing gas-rich, clumpy, extended rotating disks not dominated by spheroids.
      Cosmological simulations and clustering theory are used to explore how these
      galaxies acquired their gas. Here we report that they are 'stream-fed galaxies',
      formed from steady, narrow, cold gas streams that penetrate the shock-heated
      media of massive dark matter haloes. A comparison with the observed abundance of
      star-forming galaxies implies that most of the input gas must rapidly convert to
      stars. One-third of the stream mass is in gas clumps leading to mergers of mass
      ratio greater than 1:10, and the rest is in smoother flows. With a merger duty
      cycle of 0.1, three-quarters of the galaxies forming stars at a given rate are
      fed by smooth streams. The rarer, submillimetre galaxies that form stars even
      more intensely are largely merger-induced starbursts. Unlike destructive mergers,
      the streams are likely to keep the rotating disk configuration intact, although
      turbulent and broken into giant star-forming clumps that merge into a central
      spheroid. This stream-driven scenario for the formation of discs and spheroids is
      an alternative to the merger picture.

PMID- 19158793
TI  - High-Q surface-plasmon-polariton whispering-gallery microcavity.
AB  - Surface plasmon polaritons (SPPs) are electron density waves excited at the
      interfaces between metals and dielectric materials. Owing to their highly
      localized electromagnetic fields, they may be used for the transport and
      manipulation of photons on subwavelength scales. In particular, plasmonic
      resonant cavities represent an application that could exploit this field
      compression to create ultrasmall-mode-volume devices. A key figure of merit in
      this regard is the ratio of cavity quality factor, Q (related to the dissipation
      rate of photons confined to the cavity), to cavity mode volume, V (refs 10, 11).
      However, plasmonic cavity Q factors have so far been limited to values less than
      100 both for visible and near-infrared wavelengths. Significantly, such values
      are far below the theoretically achievable Q factors for plasmonic resonant
      structures. Here we demonstrate a high-Q SPP whispering-gallery microcavity that
      is made by coating the surface of a high-Q silica microresonator with a thin
      layer of a noble metal. Using this structure, Q factors of 1,376 +/- 65 can be
      achieved in the near infrared for surface-plasmonic whispering-gallery modes at
      room temperature. This nearly ideal value, which is close to the theoretical
      metal-loss-limited Q factor, is attributed to the suppression and minimization of
      radiation and scattering losses that are made possible by the geometrical
      structure and the fabrication method. The SPP eigenmodes, as well as the
      dielectric eigenmodes, are confined within the whispering-gallery microcavity and
      accessed evanescently using a single strand of low-loss, tapered optical
      waveguide. This coupling scheme provides a convenient way of selectively exciting
      and probing confined SPP eigenmodes. Up to 49.7 per cent of input power is
      coupled by phase-matching control between the microcavity SPP and the tapered
      fibre eigenmodes.

PMID- 19158794
TI  - Warming of the Antarctic ice-sheet surface since the 1957 International
      Geophysical Year.
AB  - Assessments of Antarctic temperature change have emphasized the contrast between
      strong warming of the Antarctic Peninsula and slight cooling of the Antarctic
      continental interior in recent decades. This pattern of temperature change has
      been attributed to the increased strength of the circumpolar westerlies, largely
      in response to changes in stratospheric ozone. This picture, however, is
      substantially incomplete owing to the sparseness and short duration of the
      observations. Here we show that significant warming extends well beyond the
      Antarctic Peninsula to cover most of West Antarctica, an area of warming much
      larger than previously reported. West Antarctic warming exceeds 0.1 degrees C per
      decade over the past 50 years, and is strongest in winter and spring. Although
      this is partly offset by autumn cooling in East Antarctica, the continent-wide
      average near-surface temperature trend is positive. Simulations using a general
      circulation model reproduce the essential features of the spatial pattern and the
      long-term trend, and we suggest that neither can be attributed directly to
      increases in the strength of the westerlies. Instead, regional changes in
      atmospheric circulation and associated changes in sea surface temperature and sea
      ice are required to explain the enhanced warming in West Antarctica.

PMID- 19158795
TI  - Anticipatory haemodynamic signals in sensory cortex not predicted by local
      neuronal activity.
AB  - Haemodynamic signals underlying functional brain imaging (for example, functional
      magnetic resonance imaging (fMRI)) are assumed to reflect metabolic demand
      generated by local neuronal activity, with equal increases in haemodynamic signal
      implying equal increases in the underlying neuronal activity. Few studies have
      compared neuronal and haemodynamic signals in alert animals to test for this
      assumed correspondence. Here we present evidence that brings this assumption into
      question. Using a dual-wavelength optical imaging technique that independently
      measures cerebral blood volume and oxygenation, continuously, in alert behaving
      monkeys, we find two distinct components to the haemodynamic signal in the alert
      animals' primary visual cortex (V1). One component is reliably predictable from
      neuronal responses generated by visual input. The other component-of almost
      comparable strength-is a hitherto unknown signal that entrains to task structure
      independently of visual input or of standard neural predictors of haemodynamics.
      This latter component shows predictive timing, with increases of cerebral blood
      volume in anticipation of trial onsets even in darkness. This trial-locked
      haemodynamic signal could be due to an accompanying V1 arterial pumping
      mechanism, closely matched in time, with peaks of arterial dilation entrained to
      predicted trial onsets. These findings (tested in two animals) challenge the
      current understanding of the link between brain haemodynamics and local neuronal
      activity. They also suggest the existence of a novel preparatory mechanism in the
      brain that brings additional arterial blood to cortex in anticipation of expected
      tasks.

PMID- 19158798
TI  - The psychosocial aspects of sexual recovery after prostate cancer treatment.
AB  - Prostate cancer affects one in six American men. Erectile and sexual dysfunctions
      are long-term side effects of prostate cancer treatment. PubMed database was
      searched for papers on prostate cancer-related sexual recovery for men and
      couples. The search yielded articles on (1) the treatment of erectile
      dysfunction, (2) men's psychological and culturally diverse adaptation to the
      sexual side effects; (3) the impact of prostate cancer on couples' relationships;
      and (4) interventions to promote sexual function. Erectile dysfunction after
      prostate cancer treatment has been widely studied. Research on the sexual
      recovery of men and couples or understanding it in a cultural context is scarce.
      Greater focus on the impact of sexual sequelae of prostate cancer treatment on
      men as well as couples in diverse groups is needed. Clinical implications for
      treating sexual dysfunction and promoting sexual recovery for prostate cancer
      survivors and their partners are discussed. Recommendations for future research
      are provided.

PMID- 19158799
TI  - Neonatal hypothermia in low resource settings: a review.
AB  - BACKGROUND: Hypothermia is increasingly recognized as a major cause of neonatal
      morbidity and mortality in resource poor settings. High prevalence of hypothermia
      has been reported widely from warmer high mortality regions of Africa and South
      Asia. The World Health Organization recognizes newborn thermal care as a critical
      and essential component of essential newborn care; however, hypothermia continues
      to remain under-documented, under-recognized and under-managed. OBJECTIVE: This
      review aims to provide a thorough patho-physio-epidemiological discussion of
      neonatal hypothermia applied to local risk factors within the developing country
      context with particular emphasis on prevention, recognition and management.
      METHOD: All available published literature on neonatal hypothermia relevant to
      resource poor settings were reviewed. Studies from the developing country
      settings were primarily reviewed for epidemiology, domiciliary risk factors as
      well as potential interventions for thermal care. RESULT AND DISCUSSION:
      Functional integrity and efficiency of biological systems is critically dependent
      on an optimal and very narrow range of core body temperature. Risk factors for
      neonatal hypothermia differ markedly within low resource settings. A combination
      of physiological, behavioral and environmental factors universally put all
      newborns, irrespective of birth weight, at risk of hypothermia. The knowledge
      deficit along the continuum from health providers to primary care givers has
      sustained the silent epidemic of hypothermia. The challenges of recognition,
      understanding of local risk factors and communication have meant a lack of
      informed thermal care for newborns. Simple, feasible interventions exist, but
      need to be applied, based on local risk factors that disrupt the warm chain.
      Further research is needed to document local risk factors, develop better
      techniques for recognition, evaluation of thermal care within essential newborn
      care and communication strategies for program effectiveness.

PMID- 19158800
TI  - Meconium aspiration syndrome remains a significant problem in the NICU: outcomes
      and treatment patterns in term neonates admitted for intensive care during a ten
      year period.
AB  - OBJECTIVE: The purpose of this study was to evaluate the demographic and
      treatment characteristics of neonates (>or=37 weeks' estimated gestational age)
      who were admitted to a neonatal intensive care unit (NICU) for a diagnosis of
      meconium aspiration syndrome (MAS) during the years 1997 to 2007. The goals in
      studying this group of neonates were to better estimate the magnitude of abnormal
      outcomes and to determine the proportion of these infants exposed to specific
      therapeutic interventions. STUDY DESIGN: Retrospective review of an
      administrative de-identified data set. RESULT: A total of 415,772 neonates formed
      the starting data set and 162,075 (39%) were >or=37 weeks. Of the 162,075 term
      neonates, 7518 (1.8% of all neonates and 4.6% of term NICU admissions) had an
      admission diagnosis of MAS. In the 7518 neonates, the following outcomes were
      observed: 6124 (81.5%) were discharged home; 679 (9%) were acutely transferred to
      a higher level of intensive care; 416 (5.5%) were transferred to another clinical
      service within the hospital; 178 (2.4%) were transferred to another NICU for
      convalescent care and 88 (1.2%) died. There were 33 (0.4%) who did not have data
      on outcome at discharge. During the period between 2002 and 2005, acute transfer
      rates decreased (12.4 to 9%) and the reported rate for death remained relatively
      constant between 0.9 and 1.5%. There were 107 (1.4%) neonates who were treated
      (n=61) with, or transferred, for extracorporeal membrane oxygenation (ECMO)
      (n=46). Three of the sixty-one neonates (4.9%) who were treated with ECMO died.
      CONCLUSION: Term neonates who are admitted with a diagnosis of MAS continue to
      represent a high-risk population with significant morbidity, and they often
      require intensive therapies.

PMID- 19158801
TI  - Albumin versus normal saline for dehydrated term infants with metabolic acidosis
      due to acute diarrhea.
AB  - To compare the efficacy of albumin to normal saline (NS) for initial hydration
      therapy for dehydrated term infants with severe metabolic acidosis due to acute
      diarrhea. STUDY DESIGN: We randomized 33 infants presenting with moderate-to
      severe dehydration and metabolic acidosis (pH <7.25 or base excess (BE) <-15)
      into two groups, an albumin group (n=15) and a NS group (n=18). For initial
      hydration treatment, the albumin group received 5% albumin (10 ml kg(-1)),
      whereas the NS group received NS (10 ml kg(-1)). RESULT: After 3 h of treatment,
      both groups improved. However, the magnitude of improvement in the pH, BE and
      HCO(3)(-) levels were not different in comparisons between these two groups. In
      addition, there were no differences either in the body weight and weight gain 4
      days after treatment or in the length of hospital stay. CONCLUSION: Albumin was
      not more effective than NS for initial hydration treatment of dehydrated term
      infants with metabolic acidosis due to acute diarrhea.

PMID- 19158803
TI  - Twins' temperament: early prenatal sonographic assessment and postnatal
      correlation.
AB  - OBJECTIVE: To study inter-twin differences in activity during early pregnancy and
      to examine their relationship to subsequent infant twins' temperament. STUDY
      DESIGN: Measures of fetal motor activity (frequency, duration and number of
      movements) were collected from 26 twin pairs during ultrasound nuchal
      translucency scan at late first trimester and early second trimester (11 to 14
      weeks gestation). In twenty-two patients, the twins were dizygotic (dichorionic);
      of them, 13 twin pairs were of different sexes, five were both females and four
      were both males. Of the four monozygotic twin pregnancies, two were dichorionic
      and two were monochorionic, three were both females.The more active fetus in each
      pair was noted according to the position and/or sex without reporting to parents.
      Reported maternal perception of the more active twin was documented at the mid
      trimester anatomical scan. Maternally reported postnatal temperament data of the
      infants were collected at 3 and 6 months, using Rothbarts' Infant Behavior
      Questionnaire (IBQ). RESULTS: After birth, maternal reports on infants'
      temperament and the more active twin in each pair were in good correlation with
      prenatal inter-twin differences in activity. The receiver operating
      characteristic (ROC) curves shows a better performance of ultrasound compared
      with maternal perception in prediction of the more active twin. CONCLUSIONS: The
      features of fetal neurobehavioral activity provide the basis for individual
      differences in twins' activity in infancy. Differences in activity in early
      pregnancy even before the emergence of fetal behavioral patterns were followed by
      temperamental differences postnatally.

PMID- 19158802
TI  - Hospitalized late preterm mild preeclamptic patients with mature lung testing:
      what are the risks of delivery?
AB  - OBJECTIVE: To evaluate the risk of elective delivery of hospitalized patients
      with isolated mild preeclampsia with mature fetal lung profile compared with a
      cohort of patients who had preeclampsia with indicated delivery matched for
      gestational age. STUDY DESIGN: Patients with mild preeclampsia requiring
      hospitalization between 34 and 37 weeks estimated gestational age were offered
      amniocentesis for assessment of fetal lung maturity. If fetal lung maturity was
      documented, patients were offered delivery. These cases were then compared with
      indicated or spontaneously delivered controls with preeclampsia matched for
      gestational age. RESULT: A total of 51 cases were identified and matched with 51
      controls. Sixteen case neonates (31.4%) were admitted to neonatal intensive care
      unit compared with 21 controls (41.2%). Five cases (9.8%) in each group developed
      respiratory distress syndrome (RDS). CONCLUSION: Elective delivery of mild
      preeclampsia with mature lung profiles in the late preterm gestation is not
      without neonatal risks, including a 10% risk of RDS in this series.

PMID- 19158804
TI  - Erythrocyte sodium/potassium ATPase activity in severe preeclampsia.
AB  - OBJECTIVE: Elevated blood levels of endogenous digitalis-like factors (EDLF) may
      decrease erythrocyte sodium pump activity in preeclampsia. As the highest EDLF
      levels might be expected in severe preeclampsia, we investigated sodium pump
      activity in that group of patients. STUDY DESIGN: Erythrocyte sodium pump
      activity was determined by (86)Rubidium uptake (in nM per hour per 10(6) cells)
      in women with severe preeclampsia and those with normal pregnancies, matched for
      gestational age, and in healthy nonpregnant women (n=12 in each group).
      Differences between groups were analyzed by a two-sided Student t-test. RESULT:
      Sodium pump activity was significantly increased in normotensive pregnancies as
      compared with normotensive non-pregnant women (81.4+/-8.4 vs 61.1+/-7.4, mean+/
      s.d., p<0.05), and was decreased 43% in severe preeclamptic pregnancies as
      compared with normotensive pregnancies (46.4+/-14.1 vs 81.4+/-8.4, p<0.05).
      CONCLUSION: Severe preeclampsia is associated with significantly lower
      erythrocyte sodium pump activity than normotensive pregnancy. These data suggest
      that plasma levels of a biologically active EDLF are elevated in patients with
      severe preeclampsia.

PMID- 19158805
TI  - Pregnancy outcome after placement of 'rescue' Shirodkar cerclage.
AB  - OBJECTIVE: Mid-trimester painless cervical dilation is associated with high rates
      of perinatal morbidity and mortality. 'Rescue' cerclage is one option in managing
      these patients. We evaluated pregnancy outcomes of women in whom we placed
      Shirodkar cerclage. STUDY DESIGN: We analyzed the pregnancy outcome of a
      retrospective cohort of women carrying singleton pregnancies who experienced late
      mid-trimester cervical dilation in whom we placed Shirodkar cerclage. Exclusion
      criteria were uterine contractions, bleeding, premature rupture of membranes and
      chorioamnionitis. Primary outcomes were gestational age at delivery, maternal,
      fetal and neonatal outcomes and surgical complications. RESULT: Between January
      2003 and December 2005, 68 patients met our inclusion criteria. The average
      maternal age was 26.4+/-8.3 years and the mean gestational age at the time of
      surgery was 19.6+/-3.2 weeks. Seven women opted for expectant management and 5
      more were followed up by their referring physicians; the 12 of them were used as
      a comparison group. Fifty-six women underwent placement of Shirodkar cerclage. We
      were unable to place a cerclage in three women (5.1%) and all three delivered
      before 23 weeks. Of the 56 women who had cerclage, 14 (23.7%) delivered at term,
      20 (33.9%) delivered between 34 and 36.9 weeks, 13 (22%) between 30 and 33.9
      weeks, 6 (10.2%) between 24 and 29.9 weeks and 3 (5.1%) before 24 weeks. Median
      time from diagnosis to delivery was longer in the cerclage group (9.1 weeks) than
      in the comparison group (3.3 weeks P<0.01). CONCLUSION: When pregnancies are
      complicated by late mid-trimester cervical dilation, placement of Shirodkar
      cerclage in appropriately selected patients has the potential to be a beneficial
      therapeutic option.

PMID- 19158806
TI  - Neonatal cerebral oximetry monitoring during ECMO cannulation.
AB  - OBJECTIVE: Neonates were monitored with a cerebral oximeter before, during, and
      after cannulation for ECMO to determine the direct effects of ligation of the
      right internal jugular vein and right carotid artery on cerebral oxygenation.
      STUDY DESIGN: After obtaining informed consent, we used the FORE-SIGHT Cerebral
      Oximeter (CAS Medical Systems, Branford, CT, USA) to monitor neonates undergoing
      surgical preparation for veno-arterial (VA) or veno-venous (VV) extracorporeal
      membrane oxygenation (ECMO). RESULT: A total of 17 subjects were monitored pre
      ECMO for at least 48 h after cannulation. Of the 17 subjects, 12 experienced low
      cerebral tissue oxygen saturation (SctO(2)) <60% during pre-ECMO surgery, with
      most exhibiting the lowest SctO(2) values between cannulation to the onset of
      ECMO. Two subjects received cardiopulmonary resuscitation (CPR) during surgery
      and experienced very low SctO(2) (5 and 36%). Pulse oximetry was found to be
      unreliable during CPR because of diminished pulsatile flow. SctO(2) increased
      above 60% after the onset of ECMO for all subjects and remained stable.
      CONCLUSION: Neonates are vulnerable to SctO(2) during the pre-ECMO surgical
      period.

PMID- 19158807
TI  - Association between CYP19A1 polymorphisms and sex hormones in postmenopausal
      Japanese women.
AB  - In postmenopausal women, extraovarian sex hormone production plays an important
      role in hormone-related diseases, such as breast and endometrial cancers.
      Aromatase, an enzyme encoded by CYP19A1, is a key enzyme involved in estrogen
      biosynthesis. The impact of CYP19A1 polymorphisms on serum sex hormone levels in
      the Japanese population has never been investigated. This study enrolled 100
      postmenopausal Japanese women found to be without cancer. Twenty-five CYP19A1
      loci were identified, and measurements were conducted on serum levels of sex
      hormones; lifestyle data were collected, namely estrone (E1), estradiol (E2),
      testosterone and sex hormone-binding globulin (SHBG). We conducted a cross
      sectional analysis to evaluate the impact of CYP19A1 haplotype on serum sex
      hormone levels. We found that subjects with BMI>or=25 kg/m(2) showed a
      significant difference in circulating testosterone levels (0.29+/-0.19, P=0.050).
      Neither age nor the amount of physical exercise or drinking habits showed any
      effect on hormone levels. We identified seven haplotype blocks in CYP19A1 by LD
      analysis. Estrone levels differed in rs12148604 (SNP 1) and rs11632903 (SNP14).
      No significant locus for estradiol was observed. SHBG levels were associated with
      rs4441215 (SNP11). Testosterone levels were strongly associated with rs752760
      (SNP24) and rs2445768 (SNP25) and weakly associated with SNP 1, SNP11 and SNP14
      as well. We found that polymorphisms in CYP19A1 influence sex hormone levels in
      Japanese postmenopausal women.

PMID- 19158808
TI  - Identification of novel EIF2B mutations in Chinese patients with vanishing white
      matter disease.
AB  - Vanishing white matter (VWM) disease, inherited in an autosomal recessive manner,
      is one of the most prevalent inherited leukoencephalopathies in childhood. It is
      a hereditary human disease resulting from the direct defects during protein
      synthesis, with the gene defects in EIF2B1-5 (identified in 2001-2002) encoding
      the five subunits of eukaryotic translation initiation factor (eIF2B alpha, beta,
      gamma, delta and epsilon), respectively. Most of the published studies were
      carried out in the white population. The analysis of clinical features and EIF2B
      mutation screening were performed in 11 Chinese patients for the first time.
      Mutations were identified exclusively in EIF2B5 and EIF2B3 in these patients,
      with six novel mutations, including five missense mutations (EIF2B5: c.185A>T,
      p.D62V; c.1004G>C, p.C335S; c.1126A>G, p.N376D; EIF2B3: c.140G>A, p.G47E;
      c.1037T>C, p.I346T) and one deletion leading to amino-acid deletion (EIF2B5:
      c.1827-1838del, p.S610-D613del). EIF2B3 mutation, accounting for 20% of the total
      number of mutations found in this study, is more prevalent than expected
      according to an earlier report (7%). A hot spot mutation in EIF2B3 was identified
      in this study. A unique EIF2B mutation spectrum in Chinese VWM patients was
      shown. A systemic study to assess mutation spectrum in different populations
      needs to be carried out.

PMID- 19158809
TI  - Case-control association study of 59 candidate genes reveals the DRD2 SNP rs6277
      (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian
      population.
AB  - The development of molecular psychiatry in the last few decades identified a
      number of candidate genes that could be associated with schizophrenia. A great
      number of studies often result with controversial and non-conclusive outputs.
      However, it was determined that each of the implicated candidates would
      independently have a minor effect on the susceptibility to that disease. Herein
      we report results from our replication study for association using 255 Bulgarian
      patients with schizophrenia and schizoaffective disorder and 556 Bulgarian
      healthy controls. We have selected from the literatures 202 single nucleotide
      polymorphisms (SNPs) in 59 candidate genes, which previously were implicated in
      disease susceptibility, and we have genotyped them. Of the 183 SNPs successfully
      genotyped, only 1 SNP, rs6277 (C957T) in the DRD2 gene (P=0.0010, odds
      ratio=1.76), was considered to be significantly associated with schizophrenia
      after the replication study using independent sample sets. Our findings support
      one of the most widely considered hypotheses for schizophrenia etiology, the
      dopaminergic hypothesis.

PMID- 19158810
TI  - Neurofilament light chain polypeptide gene mutations in Charcot-Marie-Tooth
      disease: nonsense mutation probably causes a recessive phenotype.
AB  - The neurofilament light chain polypeptide (NEFL) forms the major intermediate
      filament in neurons and axons. NEFL mutation is a cause of axonal or
      demyelinating forms of dominant Charcot-Marie-Tooth disease (CMT). We
      investigated NEFL in 223 Japanese CMT patients who were negative for PMP22, MPZ,
      GJB1, LITAF, EGR2, GDAP1, MTMR2 and PRX in the demyelinating form and negative
      for MFN2, MPZ, GJB1, HSP27, HSP22 and GARS in the axonal form. We detected four
      heterozygous missense mutations--Pro8Leu, Glu90Lys, Asn98Ser and Glu396Lys--in
      five unrelated patients and a homozygous nonsense mutation, Glu140Stop, in one
      other patient. All patients had mildly to moderately delayed nerve conduction
      velocities, possibly caused by a loss of large diameter fibers. This is the first
      report of a homozygous nonsense mutation of NEFL. Results of our study show that
      nonsense NEFL mutations probably cause a recessive phenotype, in contrast to
      missense mutations, which cause a dominant phenotype.

PMID- 19158811
TI  - Origins of the Moken Sea Gypsies inferred from mitochondrial hypervariable region
      and whole genome sequences.
AB  - The origins of the Moken 'Sea Gypsies,' a group of traditionally boat-dwelling
      nomadic foragers, remain speculative despite previous examinations from
      linguistic, sociocultural and genetic perspectives. We explored Moken origin(s)
      and affinities by comparing whole mitochondrial genome and hypervariable segment
      I sequences from 12 Moken individuals, sampled from four islands of the Mergui
      Archipelago, to other mainland Asian, Island Southeast Asian (ISEA) and Oceanic
      populations. These analyses revealed a major (11/12) and a minor (1/12) haplotype
      in the population, indicating low mitochondrial diversity likely resulting from
      historically low population sizes, isolation and consequent genetic drift.
      Phylogenetic analyses revealed close relationships between the major lineage
      (MKN1) and ISEA, mainland Asian and aboriginal Malay populations, and of the
      minor lineage (MKN2) to populations from ISEA. MKN1 belongs to a recently defined
      subclade of the ancient yet localized M21 haplogroup. MKN2 is not closely related
      to any previously sampled lineages, but has been tentatively assigned to the
      basal M46 haplogroup that possibly originated among the original inhabitants of
      ISEA. Our analyses suggest that MKN1 originated within coastal mainland SEA and
      dispersed into ISEA and rapidly into the Mergui Archipelago within the past few
      thousand years as a result of climate change induced population pressure.

PMID- 19158812
TI  - Susceptibility genes for Kawasaki disease: toward implementation of personalized
      medicine.
AB  - Kawasaki disease (KD) is an acute systemic vasculitis syndrome, which primarily
      affects in children under the age of 5 years. In 20-25% of cases, if untreated,
      coronary artery lesions develop, making KD the leading cause of acquired heart
      disease in children in both Japan and the United States. Since 1970, 19
      nationwide surveys of KD in Japan have been conducted every 2 years and the data
      are stored in a database. Even though the etiology of KD remains unknown, despite
      enthusiastic research spanning more than 40 years, we have learnt a great deal
      about KD from this enormous database. These 19 epidemiologic studies indicate a
      strong genetic influence on the disease susceptibility, prompting us and other
      researchers to identify the responsible genes for KD by applying either the
      candidate gene approach or the genome-wide approach. We have employed a genome
      wide linkage study using affected sibling pair data of KD in Japan and have
      identified several susceptibility loci. Further analysis focusing on a region of
      chromosome 19, where one of the linked loci was detected, identified a
      predisposing gene, which codes inositol 1,4,5-trisphosphate 3-kinase C (ITPKC).
      In this review, we summarize the cumulative knowledge regarding KD, and then
      outline our hypothesis of the role ITPKC plays in KD susceptibility and our trial
      that aims toward the implementation of personalized medicine for KD.

PMID- 19158813
TI  - The HLA genomic loci map: expression, interaction, diversity and disease.
AB  - The human leukocyte antigen (HLA) super-locus is a genomic region in the
      chromosomal position 6p21 that encodes the six classical transplantation HLA
      genes and at least 132 protein coding genes that have important roles in the
      regulation of the immune system as well as some other fundamental molecular and
      cellular processes. This small segment of the human genome has been associated
      with more than 100 different diseases, including common diseases, such as
      diabetes, rheumatoid arthritis, psoriasis, asthma and various other autoimmune
      disorders. The first complete and continuous HLA 3.6 Mb genomic sequence was
      reported in 1999 with the annotation of 224 gene loci, including coding and non
      coding genes that were reviewed extensively in 2004. In this review, we present
      (1) an updated list of all the HLA gene symbols, gene names, expression status,
      Online Mendelian Inheritance in Man (OMIM) numbers, including new genes, and
      latest changes to gene names and symbols, (2) a regional analysis of the extended
      class I, class I, class III, class II and extended class II subregions, (3) a
      summary of the interspersed repeats (retrotransposons and transposons), (4)
      examples of the sequence diversity between different HLA haplotypes, (5) intra-
      and extra-HLA gene interactions and (6) some of the HLA gene expression profiles
      and HLA genes associated with autoimmune and infectious diseases. Overall, the
      degrees and types of HLA super-locus coordinated gene expression profiles and
      gene variations have yet to be fully elucidated, integrated and defined for the
      processes involved with normal cellular and tissue physiology, inflammatory and
      immune responses, and autoimmune and infectious diseases.

PMID- 19158814
TI  - Genetic correlation between autistic traits and IQ in a population-based sample
      of twins with autism spectrum disorders (ASDs).
AB  - Although there is accumulating evidence that intelligence quotient (IQ) indexes
      some aspects of the autistic spectrum disorders (ASDs), the causal relationship
      between autistic traits and IQ remains controversial. We examined the sources of
      covariation between autistic traits and IQ. As males have a four times greater
      risk of ASDs than females, gender-specific effects were also explored. Autistic
      traits and IQ were assessed in 45 twin male-male, female-female and opposite-sex
      pairs ascertained by the regional screening system in Nagoya, Japan. Sex-limited
      Cholesky structural equation models were used to decompose the correlations
      between autistic traits and IQ into genetic and environmental components,
      including sex-specific factors. Genetic correlations between autistic traits and
      IQ were high and not significantly different between boys and girls (-0.94 and 
      0.95, respectively), but genetic factors underlying the autistic traits were not
      entirely shared with the IQ. The individual-specific environmental correlation
      between autistic traits and IQ was estimated at -0.29 for boys and -0.59 for
      girls. There is a substantial overlap between the genetic factors that influence
      individual variation in autistic traits and IQ, irrespective of gender. The
      individual life experiences that increase autistic traits, however, have a
      moderate overlap with those that contribute to individual IQs.

PMID- 19158815
TI  - Two-stage case-control association study of polymorphisms in rheumatoid arthritis
      susceptibility genes with schizophrenia.
AB  - There is strong evidence for a negative association between schizophrenia and
      rheumatoid arthritis (RA). However, the mechanism for this association is
      unknown. We hypothesize that these two diseases share susceptibility genes.
      Recently, extensive studies have identified some RA susceptibility genes,
      including NFKBIL1, SLC22A4, RUNX1, FCRL3 and PADI4, in the Japanese population.
      To assess whether polymorphisms in these RA susceptibility genes are implicated
      in vulnerability to schizophrenia, we conducted a two-stage case-control
      association study in Japanese subjects. In a screening population of 534 patients
      and 559 control subjects, we examined eight polymorphisms in RA susceptibility
      genes and found a potential association of padi4_94 in PADI4 with schizophrenia.
      However, we could not replicate this association in a confirmatory population of
      2126 patients and 2228 control subjects. The results of this study suggest that
      these polymorphisms in RA susceptibility genes do not contribute to genetic
      susceptibility to schizophrenia.

PMID- 19158816
TI  - The Indian origin of paternal haplogroup R1a1* substantiates the autochthonous
      origin of Brahmins and the caste system.
AB  - Many major rival models of the origin of the Hindu caste system co-exist despite
      extensive studies, each with associated genetic evidences. One of the major
      factors that has still kept the origin of the Indian caste system obscure is the
      unresolved question of the origin of Y-haplogroup R1a1*, at times associated with
      a male-mediated major genetic influx from Central Asia or Eurasia, which has
      contributed to the higher castes in India. Y-haplogroup R1a1* has a widespread
      distribution and high frequency across Eurasia, Central Asia and the Indian
      subcontinent, with scanty reports of its ancestral (R*, R1* and R1a*) and derived
      lineages (R1a1a, R1a1b and R1a1c). To resolve these issues, we screened 621 Y
      chromosomes (of Brahmins occupying the upper-most caste position and schedule
      castes/tribals occupying the lower-most positions) with 55 Y-chromosomal binary
      markers and seven Y-microsatellite markers and compiled an extensive dataset of
      2809 Y-chromosomes (681 Brahmins, and 2128 tribals and schedule castes) for
      conclusions. A peculiar observation of the highest frequency (up to 72.22%) of Y
      haplogroup R1a1* in Brahmins hinted at its presence as a founder lineage for this
      caste group. Further, observation of R1a1* in different tribal population groups,
      existence of Y-haplogroup R1a* in ancestors and extended phylogenetic analyses of
      the pooled dataset of 530 Indians, 224 Pakistanis and 276 Central Asians and
      Eurasians bearing the R1a1* haplogroup supported the autochthonous origin of R1a1
      lineage in India and a tribal link to Indian Brahmins. However, it is important
      to discover novel Y-chromosomal binary marker(s) for a higher resolution of R1a1*
      and confirm the present conclusions.

PMID- 19158817
TI  - Identification of multidrug and toxin extrusion (MATE1 and MATE2-K) variants with
      complete loss of transport activity.
AB  - H(+)/organic cation antiporters (multidrug and toxin extrusion: MATE1 and MATE2
      K) play important roles in the renal tubular secretion of cationic drugs. We have
      recently identified a regulatory single nucleotide polymorphism (SNP) of the
      MATE1 gene (-32G>A). There is no other information about SNPs of the MATE gene.
      In this study, we evaluated the functional significance of genetic polymorphisms
      in MATE1 and MATE2-K. We sequenced all exons of MATE1 and MATE2-K genes in 89
      Japanese subjects and identified coding SNPs (cSNPs) encoding MATE1 (V10L, G64D,
      A310V, D328A and N474S) and MATE2-K (K64N and G211V). All the variants except for
      MATE1 V10L showed significant decrease in transport activity. In particular,
      MATE1 G64D and MATE2-K G211V variants completely lost transport activities. When
      membrane expression level was evaluated by cell surface biotinylation, those of
      MATE1 (G64D and D328A) and MATE2-K (K64N and G211V) were significantly decreased
      compared with that of wild type. These findings suggested that the loss of
      transport activities of the MATE1 G64D and MATE2-K G211V variants were due to the
      alteration of protein expression in cell surface membranes. This is the first
      demonstration of functional impairment of the MATE family induced by cSNPs.

PMID- 19158818
TI  - DNA variations in human and medical genetics: 25 years of my experience.
AB  - DNA variations have contributed enormously to the fields of medical and forensic
      science, especially through their use in studies on genes responsible or
      susceptible to various diseases and those on screening of chromosomal
      abnormalities in tumors. The types of genetic variations used in these studies
      have changed in the past 25 years and can be classified into five major classes:
      RFLP (restriction fragment length polymorphism), VNTR (variable number of tandem
      repeat), STR (short tandem repeat or microsatellite), SNP (single-nucleotide
      polymorphism) and CNV (copy-number variation). Genetic linkage analysis using
      these tools helped to map and discover genes responsible for hundreds of
      hereditary diseases. Furthermore, construction of the international SNP database
      and recent development of high-throughput SNP typing platforms enabled us to
      perform genome-wide association studies, which have identified genes (or genetic
      variations) susceptible to common diseases or those associated with drug
      responses. Genome-wide sequencing of individual DNAs is gaining immense scope.
      Here, I summarize the history of polymorphic DNA markers and their contribution
      to the genetic analysis of both rare hereditary diseases and common diseases, as
      well as recent advances in pharmacogenetics, including our contribution to these
      areas.

PMID- 19158819
TI  - New findings from genetic association studies of schizophrenia.
AB  - In the past 20 years, association studies of schizophrenia have evolved from
      analyses in lesser than 100 subjects of one or two markers in candidate genes to
      systematic analyses of association at a genome-wide level in samples of thousands
      of subjects. During this process, much of the emergent literature has been
      difficult to interpret and definitive findings that have met with universal
      acceptance have been elusive, largely because studies have been underpowered for
      such conclusions to be drawn. Nevertheless, in the course of the past few years,
      a few promising candidate genes have been reported for which the evidence is
      positive across multiple studies, and more recently, genome-wide association
      studies have yielded findings of a compelling nature. It is clear that genetic
      studies in schizophrenia have borne fruit, a process that can be expected to
      accelerate in the next few years, and that these findings are providing new
      avenues for research into the pathophysiology of this poorly understood disorder.

PMID- 19158820
TI  - Characterization of deletion breakpoints in patients with dystrophinopathy
      carrying a deletion of exons 45-55 of the Duchenne muscular dystrophy (DMD) gene.
AB  - Deletion of exons 45-55 (del45-55) in the Duchenne muscular dystrophy gene (DMD)
      has gained particular interest in the field of molecular therapy, because it
      causes a milder phenotype than DMD, and therefore, may represent a good candidate
      for the goal of a multiple exon-skipping strategy. We have precisely
      characterized deletion breakpoints in three patients with del45-55 in DMD. Two of
      them were young adult males of the X-linked dilated cardiomyopathy phenotype, and
      the third patient revealed the mild Becker muscular dystrophy phenotype of late
      onset. The deletion breakpoints differed among patients. The deletion started at
      nt 226 604, 231 518, 117 284 in intron 44, and ended at nt 64 994, 59 314, 71 806
      in intron 55, respectively. Deletion junctions showed no significant homology
      between the sequences adjacent to the distal and proximal end joints in these
      patients. Deletion breakpoints were not primarily associated with any particular
      sequence element, or with a matrix attachment region. However, there were several
      palindromic sequences and short tandem repeats at or near the breakpoints. These
      sequences, with a marked propensity to form secondary DNA structure
      intermediates, may predispose local DNA to breakage and intragenic recombination
      in these patients.

PMID- 19158822
TI  - Blood pressure variability and prevalence of hypertension using automated
      readings from multiple visits to a pharmacy-based community-wide programme.
AB  - Blood pressure (BP) measurements taken outside the routine office context may be
      a useful adjunct strategy to monitor BP. Community-based BP data can also provide
      estimates of the prevalence of elevated BP. We compared multiple readings taken
      on different days in pharmacies using an automated BpTRU device during a
      cardiovascular health programme targeting community-dwelling older adults. Mean
      systolic (S) and diastolic (D) BP values were compared over time using repeated
      measures analysis of variance for all participants with at least three separate
      sets of readings (n=317). BP variability was then examined among four subgroups
      based on report of antihypertensive medication or no treatment, and normal or
      elevated SBP at the initial visit (< or >or=140, or 130 if diabetes reported).
      Prevalence of elevated BP was compared across visits. Overall, mean SBP decreased
      between visits 1 and 2 (140.4 vs 137.1 mm Hg; P<0.001). Among participants with
      normal SBP at the initial visit, SBP did not vary significantly, whether or not
      antihypertensive treatment was reported. Those with initially elevated SBP
      experienced a significant decrease between visits 1 and 2, also regardless of
      treatment status. Prevalence of elevated BP decreased from visits 1 to 2 (55.8 vs
      48.9%; P=0.026) and from visits 1 to 3 (55.8 vs 42.9%; P<0.001). Analyses of BP
      data from a community-based programme using an accurate device showed that
      initial readings may inflate the population estimate of elevated BP. Findings
      suggest that more than one set of BP readings measured on different occasions are
      needed, particularly if the first set is elevated.

PMID- 19158821
TI  - Oral contraceptive progestins and angiotensin-dependent control of the renal
      circulation in humans.
AB  - Oral contraceptive (OC) use is associated with increased intrarenal renin
      angiotensin-aldosterone system (RAA System) activity and risk of nephropathy,
      though the contribution of progestins contained in the OC in the regulation of
      angiotensin-dependent control of the renal circulation has not been elucidated. A
      total of 18 OC users (8 non-diabetic, 10 Type 1 diabetic) were studied in high
      salt balance, a state of maximal RAA System suppression. Progestational and
      androgenic activity of the progestin in each OC was standardized to that of the
      reference progestin norethindrone. Renal plasma flow (RPF) was measured by para
      aminohippurate clearance at baseline and in response to angiotensin-converting
      enzyme (ACE) inhibition. There was a positive correlation between OC
      progestational activity and the RPF response to ACE inhibition (r=0.52, P=0.03).
      Similar results were noted with OC androgenic activity (r=0.54, P=0.02). On
      subgroup analysis, only non-diabetic subjects showed an association between
      progestational activity and angiotensin-dependent control of the renal
      circulation (r=0.71, P=0.05 non-diabetic; r=0.14, P=0.7 diabetic; P=0.07 between
      groups). Similar results were noted with respect to androgenic activity (r=0.88,
      P=0.005 non-diabetic; r=-0.33, P=0.3 diabetic; P=0.002 between groups). Our
      results suggest that the OC progestin component is a significant influence on the
      degree of angiotensin-dependent control of the renal circulation, though these
      findings may not apply to women with diabetes.

PMID- 19158823
TI  - The message for World Kidney Day 2009: hypertension and kidney disease--a
      marriage that should be prevented.
AB  - The prevalence of chronic kidney disease (CKD) continues to increase worldwide as
      does end stage renal disease. The most common, but not the only, causes of CKD
      are hypertension and diabetes. CKD is associated with a significant increase in
      cardiovascular (CV) risk as most patients with CKD die of a CV cause. Moreover,
      CV risk increases proportionally as eGFR falls below 60 ml min(-1). CV causes of
      death in CKD are more prevalent than those from cancer are; as a result, the
      identification and reduction of CKD is a public health priority. High blood
      pressure is a key pathogenic factor that contributes to the deterioration of
      kidney function. The presence of kidney disease is a common and underappreciated
      pre-existing medical cause of resistant hypertension. Therefore, treatment of
      hypertension has become the most important intervention in the management of all
      forms of CKD. For this reason, the forthcoming World Kidney Day on 12 March 2009
      will emphasize the role of hypertension.

PMID- 19158825
TI  - Trends in high blood pressure prevalence in Greek adolescents.
AB  - A school-based screening with anthropometric and blood pressure (BP) measurements
      was performed in adolescents aged 12-17 years in the island of Samos, Greece, in
      2004 and also in 2007. A total of 446 adolescents were included in the analysis
      in 2004 and 558 in 2007. The 2007 study population had higher levels of body mass
      index (BMI) (P<0.05) and systolic and diastolic BP (P<0.001), compared with 2004.
      The prevalence of high BP was 16.1% in 2004 and 22.9% in 2007 (P<0.01 for
      difference). Mean age-, sex- and BMI-adjusted BP increase was 4.1/10.5 mm Hg
      (systolic/diastolic). In multivariate analysis, BMI, male gender and age, but
      also modifiable factors (lack of physical activity, breakfast skipping, smoking
      and low milk consumption) were associated with increased BP levels in the study
      population. These data indicate that further to BMI, other factors such as
      adverse lifestyle and dietary habits appear to be associated with elevated BP
      levels in adolescents. Moreover, rising trends seem to characterize the
      prevalence of high BP.

PMID- 19158826
TI  - Blood pressure lowering efficacy of renin inhibitors for primary hypertension: a
      Cochrane systematic review.
AB  - We conducted a systematic review and meta-analysis of double-blind randomized
      controlled trials to quantify the dose-related systolic (SBP) and diastolic blood
      pressure (DBP) lowering efficacy of renin inhibitors vs placebo in the treatment
      of adults with primary hypertension. Databases searched were Medline (1966-March
      2008), EMBASE (1988-March 2008) and Cochrane Central Register of Controlled
      Trials (CENTRAL). Six trials in 3694 patients met the inclusion criteria. All
      examined aliskiren, the only renin inhibitor licensed for marketing in Canada and
      the United States. Aliskiren caused a dose-related SBP/DBP lowering effect
      compared to placebo: weighted mean difference with 95% CI: aliskiren 75 mg, -2.9
      (-4.6, -1.3)/-2.3 (-3.3, -1.3) mm Hg; aliskiren 150 mg, -5.5 (-6.5, -4.4)/-3.0 (
      3.7, -2.3) mm Hg; aliskiren 300 mg, -8.7 (-9.7,-7.6)/-5.0 (-5.6, -4.3) and
      aliskiren 600 mg, -11.4 (-13.5, -9.2)/-6.6 (-7.9, -5.2) mm Hg. Aliskiren 300 mg
      significantly lowered both SBP -3.0 (-4.0, -2.0) and DBP -1.7 (-2.3, -1.0) as
      compared to aliskiren 150 mg. Aliskiren has no effect on blood pressure
      variability. No data were available to assess the effect of aliskiren on heart
      rate or pulse pressure. This review found weak evidence that during 4- to 8-week
      use, aliskiren did not increase withdrawals due to adverse effects as compared to
      placebo. We concluded that aliskiren has a dose-related blood pressure lowering
      effect better than placebo and magnitude of effect is similar to that determined
      for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

PMID- 19158827
TI  - Genomic tools for dissecting oncogenic transcriptional networks in human
      leukemia.
AB  - Chromatin immunoprecipitation (ChIP)-chip and ChIP-seq technologies are rapidly
      expanding our capacity to interrogate the location of transcription factor
      binding sites in the human genome and to map the pattern of chromatin
      modifications associated with the regulation of gene expression. The application
      of these techniques to the study of hematologic malignancies will complement gene
      expression profiling studies to elucidate the structure and function of oncogenic
      transcriptional networks involved in the pathogenesis of leukemias and lymphomas.

PMID- 19158828
TI  - Quantification of fusion transcript reveals a subgroup with distinct biological
      properties and predicts relapse in BCR/ABL-positive ALL: implications for
      residual disease monitoring.
AB  - Minimal residual disease (MRD) monitoring is an essential tool for risk group
      stratification in current treatment protocols for childhood acute lymphoblastic
      leukaemia (ALL). Although quantitative detection of clonal immunoglobulin (Ig)
      and T-cell receptor (TCR) gene rearrangements is currently considered to be the
      standard method, leukaemia fusion genes provide other possible targets for MRD
      follow-up, as already demonstrated in TEL/AML1-positive ALLs. We analysed and
      compared MRD levels quantified by BCR/ABL transcript detection and by the
      standard Ig/TCR-based method in 218 bone marrow specimens from 17 children with
      BCR/ABL-positive ALL. We found only a limited overall correlation of MRD levels
      as assessed by the two methods (correlation coefficient R(2)=0.64). The
      correlation varied among patients from excellent (R(2)=0.99) to very poor
      (R(2)=0.17). Despite identical sensitivity of the approaches, 20% of the samples
      were negative by the Ig/TCR approach whereas positive by the BCR/ABL method. We
      show that multilineage involvement is at least partly responsible for the
      discrepancy. Moreover, our data demonstrate that BCR/ABL monitoring enables
      better and earlier prediction of relapse compared to the standard Ig/TCR
      methodology. We conclude that BCR/ABL-based MRD monitoring of childhood ALL is a
      clinically relevant tool and should be performed in parallel with the standard
      Ig/TCR follow-up.

PMID- 19158829
TI  - The level of AKT phosphorylation on threonine 308 but not on serine 473 is
      associated with high-risk cytogenetics and predicts poor overall survival in
      acute myeloid leukaemia.
AB  - The phosphoinositide 3-kinase/Akt pathway is an important signalling pathway
      governing cell survival and proliferation in acute myeloid leukaemia (AML). As
      full activation of Akt requires phosphorylation on both threonine 308 (Thr308)
      and serine 473 (Ser473) residues, we studied the level of phosphorylation on the
      both sites in 58 AML samples by flow cytometry. The ratio of the mean
      fluorescence intensity of Thr308 and Ser473 represented a continuum ranging from
      0.3 to 5.6 and from 0.4 to 2.87, respectively. There were no significant
      correlations between age, gender, French-American-British classification,
      leukocytosis, FLT3-ITD and Akt phosphorylation. However, the level of
      phosphorylation on Thr308, but not on Ser473, was significantly correlated with
      high-risk karyotype. Thr308(high) patients had significantly shorter overall
      survival (11 vs 47 months; P=0.01), event-free survival (9 vs 26 months; P=0.005)
      and relapse-free survival (10 months vs not reached; P=0.02) than Thr308(low)
      patients. Neither screening for AKT1 E17K mutation nor changes in the level of
      PTEN expression and phosphorylation could be linked to increased phosphorylation
      on Thr308 in high-risk cytogenetic AML cells. However, PP2A activity was
      significantly reduced in high-risk samples compared with intermediate-risk
      samples. Moreover, the specific Akt inhibitor, Akti-1/2, inhibited cell
      proliferation and clonogenic properties, and induced apoptosis in AML cells with
      high-risk cytogenetics, suggesting that Akt may represent a therapeutic target in
      high-risk AML.

PMID- 19158830
TI  - miR-34a, miR-29c and miR-17-5p are downregulated in CLL patients with TP53
      abnormalities.

PMID- 19158831
TI  - MLL/AF-4 leukemic cells recruit new blood vessels but do not incorporate into
      capillaries in culture or in a NOD/SCID xenograft model.

PMID- 19158832
TI  - The hematopoietic stem cell in chronic phase CML is characterized by a
      transcriptional profile resembling normal myeloid progenitor cells and reflecting
      loss of quiescence.
AB  - We found that composition of cell subsets within the CD34+ cell population is
      markedly altered in chronic phase (CP) chronic myeloid leukemia (CML).
      Specifically, proportions and absolute cell counts of common myeloid progenitors
      (CMP) and megakaryocyte-erythrocyte progenitors (MEP) are significantly greater
      in comparison to normal bone marrow whereas absolute numbers of hematopoietic
      stem cells (HSC) are equal. To understand the basis for this, we performed gene
      expression profiling (Affymetrix HU-133A 2.0) of the distinct CD34+ cell subsets
      from six patients with CP CML and five healthy donors. Euclidean distance
      analysis revealed a remarkable transcriptional similarity between the CML
      patients' HSC and normal progenitors, especially CMP. CP CML HSC were
      transcriptionally more similar to their progeny than normal HSC to theirs,
      suggesting a more mature phenotype. Hence, the greatest differences between CP
      CML patients and normal donors were apparent in HSC including downregulation of
      genes encoding adhesion molecules, transcription factors, regulators of stem-cell
      fate and inhibitors of cell proliferation in CP CML. Impaired adhesive and
      migratory capacities were functionally corroborated by fibronectin detachment
      analysis and transwell assays, respectively. Based on our findings we propose a
      loss of quiescence of the CML HSC on detachment from the niche leading to
      expansion of myeloid progenitors.

PMID- 19158833
TI  - Recurrent genomic aberrations combined with deletions of various tumour
      suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic
      neoplasms and contribute to the aggressiveness of the disease.
AB  - CD4+CD56+ haematodermic neoplasms (HDN) constitute a rare disease characterized
      by aggressive clinical behaviour and a poor prognosis. Tumour cells from HDN are
      leukaemic counterparts of plasmacytoid dendritic cells (pDCs). Despite increased
      knowledge of the ontogenetic origin of these tumours, the genetic causes and
      oncogenic signalling events involved in malignant transformation are still
      unknown. To delineate novel candidate regions and disease-related genes, we
      studied nine typical CD4+CD56+ HDN cases using genome-wide high-resolution array
      comparative genomic hybridization (CGH). Genomic imbalances, which were
      predominantly losses, were frequently detected. Gross genomic losses or gains
      involving an entire chromosome were observed in eight cases. The most frequent
      imbalances were deletions of chromosome 9, chromosome 13 and partial losses
      affecting 17p or 12p. Combinations of deletions of tumour suppressor genes (TSG),
      namely RB1, CDKN1B (p27), CDKN2A, (p16(ink4a), p14(arf)) or TP53 (p53), were
      observed in all cases. These results indicate that deletion events altering G1/S
      regulation are crucial for HDN oncogenesis. Furthermore, in addition to frequent
      sporadic gene losses, in one case we observed a 8q24 interstitial deletion that
      brought MYC closer to miR-30b/miR-30d, which may be related to their
      deregulation. Taken together, these results indicate that in addition to frequent
      G1/S checkpoint alterations, various genetic events could contribute to the
      chemoresistance of the tumour.

PMID- 19158835
TI  - Depletion of L-asparagine supply and apoptosis of leukemia cells induced by human
      glycosylasparaginase.

PMID- 19158834
TI  - The stem cell factor-c-KIT pathway must be inhibited to enable apoptosis induced
      by BCR-ABL inhibitors in chronic myelogenous leukemia cells.
AB  - Imatinib is an effective first-line therapy for chronic myelogenous leukemia
      (CML) that acts by targeting the tyrosine kinase activity of BCR-ABL. To overcome
      resistance, second-generation inhibitors of BCR-ABL have been developed. Among
      these, nilotinib is more potent against BCR-ABL than imatinib, and is effective
      against many imatinib-resistant BCR-ABL mutants. In this study, an in vitro flow
      cytometry assay to analyze imatinib- and nilotinib-induced apoptosis in CML cells
      has been developed. Both the drugs induced significant apoptosis in CD34+ cells
      from 36 CML bone marrow samples (P<10(-4)), whereas CD34+ cells from BCR-ABL
      negative samples were unaffected. When the experiments were carried out in the
      presence of a cocktail of cytokines, nilotinib- but not imatinib-induced
      apoptosis was inhibited. This differential inhibition was confirmed on K562
      cells. A blocking anti-CD117 antibody alleviated the antiapoptotic effect of
      cytokines against nilotinib. Moreover, using short hairpin RNA against BCR-ABL,
      we showed that K562 cells were not dependent on BCR-ABL signaling as long as the
      stem cell factor (SCF) receptor pathway was activated. We conclude that the c-KIT
      pathway may substitute for BCR-ABL tyrosine kinase to activate survival signals,
      and that c-KIT must be inhibited besides Bcr-Abl to allow apoptosis of CML cells.

PMID- 19158836
TI  - Therapy-related acute myeloid leukaemia with t(8;16)(p11;p13);MOZ-CBP and
      polymorphisms in detoxifying and DNA repair genes.

PMID- 19158837
TI  - The homeobox gene CDX2 is aberrantly expressed and associated with an inferior
      prognosis in patients with acute lymphoblastic leukemia.
AB  - Molecular characterization of acute lymphoblastic leukemia (ALL) has greatly
      improved the ability to categorize and prognostify patients with this disease. In
      this study, we show that the proto-oncogene CDX2 is aberrantly expressed in the
      majority of cases with B-lineage ALL and T-ALL. High expression of CDX2
      correlated significantly with the ALL subtype pro-B ALL, cALL, Ph(+) ALL and
      early T-ALL. Furthermore, high expression of CDX2 was associated with inferior
      overall survival and showed up as a novel and strong risk factor for ALL in
      bivariate analysis. Functional analyses showed that overexpression of Cdx2 in
      murine bone marrow progenitors perturbed genes involved in lymphoid development
      and that depletion of CDX2 in the human ALL cell line Nalm6 inhibited colony
      formation. These data indicate that aberrant CDX2 expression occurs frequently
      and has prognostic impact in adult patients with ALL.

PMID- 19158838
TI  - Atypical 11q deletions identified by array CGH may be missed by FISH panels for
      prognostic markers in chronic lymphocytic leukemia.

PMID- 19158839
TI  - Profiling the response of human hair follicles to ultraviolet radiation.
AB  - Excessive UVR ranks among the most harmful environmental influences on human
      skin. However, the direct impact of UVR on human skin appendages remains to be
      systematically investigated. Organ-cultured human anagen hair follicles in vitro
      were irradiated, and reduction of hair shaft elongation, premature catagen entry,
      and reduced hair matrix keratinocyte proliferation were observed upon irradiation
      with UVB (20/50 mJ cm(-2)). At 20 mJ cm(-2), apoptotic cell death prevailed (casp
      3/p53 activation), whereas at 50 mJ cm(-2), necrotic cell death was predominant
      (lactate dehydrogenase increase). Mitochondrial common deletion and oxidatively
      damaged genomic DNA (8-OH-dG) was mainly observed at 20 mJ cm(-2). Follicular
      melanogenesis and ACTH immunoreactivity drastically declined, but alpha
      melanocyte-stimulating hormone remained unchanged, whereas transforming growth
      factor-beta(2) expression shifted from the outer toward the inner root sheath.
      Both the number of Giemsa+ mast cells and the degree of mast-cell degranulation
      increased in the connective tissue sheath (CTS), and CD117 immunoreactivity of
      CTS cells and matrix keratinocytes was upregulated. Thus, UVR differentially
      modifies hair growth and cycle, promotes cell death, and induces complex
      regulatory events in human hair follicles in vitro. The leads from this human
      organ model, which is a living and human tissue interaction system under
      physiologically relevant in situ conditions, may encourage its use for general
      investigation of UV-induced effects as well as for testing possible agents for
      their UV-protective potency.

PMID- 19158840
TI  - Induction of autoimmunity in a bleomycin-induced murine model of experimental
      systemic sclerosis: an important role for CD4+ T cells.
AB  - Systemic sclerosis (SSc) is an autoimmune disease characterized by the excessive
      deposition of collagen in the skin or other organs and the production of specific
      antinuclear antibodies (ANAs). Recently, bleomycin (BLM)-induced experimental
      scleroderma was reported in a murine model. Here, we present further development
      of this model and suggest that it is appropriate for the analysis of human
      diffuse type SSc. BLM was injected into the shaved backs of C3H or BALB/c mice
      (100 microg/mouse) 5 days per week for 3 weeks. Skin fibrosis was confirmed and
      pathological changes were seen in the lower part of the esophagus and stomach
      similar to those seen in SSc. The sera from these mice had autoantibodies
      specific to the damaged tissues and ANAs. Transfer of CD4(+) T cells from BLM
      treated BALB/c mice induced the same pathological changes and antibody production
      in untreated-BALB/c nude mice. Hence, tissue fibrosis and the production of ANAs
      are probably associated with CD4(+) T-cell activity in this model. In conclusion,
      this model will be valuable for investigating the relationship between tissue
      fibrosis and abnormalities of the immune system.

PMID- 19158841
TI  - Cutaneous melanoma in childhood and adolescence shows frequent loss of INK4A and
      gain of KIT.
AB  - Childhood cutaneous melanoma is a rare disease with increasing incidence. It is
      not clear whether it differs from adult melanoma in etiology and clinical
      evolution. To genetically characterize childhood melanoma, 21 pediatric patients
      were studied by germ-line analysis of CDKN2A, CDK4, and MC1R genes. In addition,
      alterations in CDKN2A, c-Kit, BRAF, and NRAS genes were evaluated at the somatic
      level by direct gene sequencing, fluorescence in situ hybridization analysis, and
      immunohistochemistry. As a control group of susceptible patients, we studied
      patients from 23 melanoma-prone families. At the germ-line level, CDKN2A and MC1R
      gene variants were detected in 2/21 and 12/21 pediatric patients and in 9/23 and
      19/22 in familial patients. At the somatic level, most lesions (9/14) from
      pediatric patients showed CDKN2A locus homozygous deletions and a null p16
      immunophenotype, whereas most lesions (5/8) from familial patients were disomic
      and immunoreactive. A c-Kit low-polysomy profile seems to parallel CDKN2A
      homozygous deletions in pediatric melanoma whereas the single activating mutation
      observed segregates with familial patients. Loss of KIT protein expression was
      frequent (7/14) in pediatric melanomas, where metastatic cases were prevalent.
      BRAF(V600E) mutation occurred at a similar rate (approximately 50%) in lesions
      from pediatric and familial patients, whereas no NRAS mutations were detected.

PMID- 19158842
TI  - Plasmin plays a role in the in vitro generation of the linear IgA dermatosis
      antigen LADB97.
AB  - Collagen XVII (BP180) and its shed ectodomain represent major autoantigens in
      dermatoses of the pemphigoid group. The 120 kDa ectodomain is constitutively shed
      from the cell surface by disintegrin-metalloproteinases (ADAMs). Part of it is
      further processed to a 97 kDa fragment (LABD97), an autoantigen in linear IgA
      dermatosis (LAD), but the responsible proteinases remain elusive. In this study,
      we identified the 120 and the 97 kDa ectodomain in blister fluids of bullous
      pemphigoid patients using new mAbs. As blister fluids contain significant plasmin
      like serine protease activity, HaCaT keratinocytes or purified 120 kDa ectodomain
      were incubated with several human serine proteases. In vitro, only plasmin
      generated a stable 97 kDa fragment that was also targeted by LAD sera.
      Characterization of the plasmin-derived 97 kDa fragment with domain-specific
      collagen XVII antibodies, heparin binding and N-glycosylation studies indicates
      that the N-terminus is located approximately at AA 515 and the C-terminus N
      terminally from AA 1,421. Interestingly, plasmin-derived LABD97 was also
      generated in the presence of ADAM inhibitors and remained stable over more than
      12 hours incubation at 37 degrees C, indicating that this disease relevant
      collagen XVII fragment can also arise in an ADAM-independent manner through
      direct action by plasmin.

PMID- 19158843
TI  - Loss of the desmosomal protein perp enhances the phenotypic effects of pemphigus
      vulgaris autoantibodies.
AB  - Pemphigus vulgaris (PV) is an autoimmune bullous disease in which autoantibodies
      against proteins of the desmosomal adhesion complex perturb desmosomal function,
      leading to intercellular adhesion defects in the oral mucosa and skin. Previous
      studies have demonstrated a central role for downregulation of the desmosomal
      cadherin desmoglein 3 (DSG3) in the pathogenesis of PV. However, the effects of
      non-cadherin desmosomal proteins in modulating the cellular manifestations of PV
      remain poorly understood. Here, we characterize the expression and functional
      importance of Perp, a newly discovered tetraspan desmosomal protein, in PV. Our
      data demonstrate that PV autoantibodies disrupt Perp expression at the membrane
      and trigger its internalization along with DSG3 into the endosomal pathway, where
      it is ultimately targeted to the lysosome for degradation. We further show that
      Perp deficiency exacerbates the pathogenic effects of PV autoantibodies on
      keratinocytes by enhancing both the depletion of desmosomal DSG3 and
      intercellular adhesion defects. Together, our findings highlight the importance
      of non-cadherin desmosomal proteins in modulating PV phenotypes and provide new
      insight into Perp's role in the desmosome.

PMID- 19158844
TI  - Redox-dependent translocation of p53 to mitochondria or nucleus in human
      melanocytes after UVA- and UVB-induced apoptosis.
AB  - The p53 protein is an important transcription factor and tumor suppressor that is
      induced in response to many forms of cellular stress. UVA irradiation of human
      melanocytes caused generation of reactive oxygen species, which altered the
      intracellular redox balance and was accompanied by translocation of p53 to
      mitochondria. In contrast, UVB did not affect the redox status and p53 was
      translocated to the nucleus. Although different intracellular location of p53,
      UVA/B induced apoptosis through the intrinsic pathway detected as translocation
      of Bax to mitochondria, release of cytochrome c, and activation of caspases.
      These events were all prevented by inhibition of p53 with pifithrin-alpha.
      Furthermore, inhibition of p53 prevented lysosomal membrane permeabilization,
      detected as translocation of cathepsins to the cytosol, after UVB exposure,
      whereas UVA-induced lysosomal release was unaffected by inhibition of p53. In
      control cells, p53 coimmunoprecipitated with the antiapoptotic proteins Bcl-2 and
      Bcl-x(L) and upon UVA exposure the interaction was replaced by binding to the
      proapoptotic proteins Bax, Noxa, and Puma. Our findings suggest that UVA-induced
      apoptosis is caused by extensive oxidative damage leading to p53-regulated
      mitochondrial release, whereas UVB induces DNA damage and apoptosis signaling
      upstream of lysosomal membrane permeabilization.

PMID- 19158845
TI  - Psoriasis and osteoporosis: a sex-specific association?
AB  - Previous reports showed associations between psoriasis and chronic diseases.
      Little is known about the association between osteoporosis and psoriasis. The
      goal of the study was to assess the association between psoriasis and
      osteoporosis in a population-based case-control study, utilizing the database of
      a large health-care provider organization in Israel, Clalit Health Services.
      Patients (aged 51-90 years) diagnosed with psoriasis were compared with a sample
      of age- and sex-matched enrollees without psoriasis regarding the prevalence of
      osteoporosis. Data on health-related lifestyles and other comorbidities were
      collected. The study included 7,936 psoriasis cases and 14,835 controls. The
      prevalence of osteoporosis was significantly greater in males with psoriasis
      compared with the control group (3.1 vs 1.7%, P<0.001, odds ratio (OR)=1.86, 95%
      confidence interval (CI): 1.44-2.39) and slightly greater in females with
      psoriasis (22.3 vs 20.2%, P=0.008, OR=1.13, 95% CI: 1.03-1.25). A multivariate
      logistic regression model demonstrated that after controlling for confounders,
      psoriasis was significantly associated with osteoporosis in males (adjusted
      OR=1.70, 95% CI: 1.31-2.19, P<0.001). The weak association between psoriasis and
      osteoporosis in females lost statistical significance in a multivariate model
      (adjusted OR=1.09, 95% CI: 0.98-1.21, P=0.100). Psoriasis was found to be
      associated with osteoporosis among males, but not among females.

PMID- 19158846
TI  - Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T
      cells for use in the adoptive immunotherapy of cancer.
AB  - Human T lymphocytes can be redirected with a new defined specificity by
      expression of a chimeric T-cell receptor (immunoreceptor) for the use in adoptive
      immunotherapy of cancer. Whereas standard procedures use retroviral gene
      transduction to constitutively express immunoreceptors in T cells, we here
      explored for the first time mRNA electroporation to achieve transient
      immunoreceptor expression, and thereby minimizing the risk of persistence of
      potential autoaggression. CD4(+) and CD8(+) T cells were efficiently transfected
      with immunoreceptors specific for ErbB2 and CEA. The immunoreceptor expression
      was transient with half-maximal expression at day 2 and no detectable
      immunoreceptor expression at day 9 after electroporation. Immunoreceptor
      transfected T cells were specifically activated upon coincubation with ErbB2(+)
      and CEA(+) tumor cells, respectively, resulting in secretion of interferon-gamma
      (IFNgamma), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNFalpha).
      Furthermore, immunoreceptor-transfected CD8(+) T cells specifically lysed
      ErbB2(+) and CEA(+) tumor cells, respectively. The RNA-transfected T cells
      retained their cytotoxic function after 2 days of activation and exhibited
      cytolytic activities like retrovirally transduced T cells. RNA electroporation of
      T cells thereby provides a versatile tool for transient immunoreceptor
      expression, which may be of advantage in avoiding the persistence of unintended
      autoaggression.

PMID- 19158847
TI  - Efficient gene delivery to the adult and fetal CNS using pseudotyped non
      integrating lentiviral vectors.
AB  - Non-integrating lentiviral vectors show considerable promise for gene therapy
      applications as they persist as long-term episomes in non-dividing cells and
      diminish risks of insertional mutagenesis. In this study, non-integrating
      lentiviral vectors were evaluated for their use in the adult and fetal central
      nervous system of rodents. Vectors differentially pseudotyped with vesicular
      stomatitis virus, rabies and baculoviral envelope proteins allowed targeting of
      varied cell populations. Efficient gene delivery to discrete areas of the brain
      and spinal cord was observed following stereotactic administration. Furthermore,
      after direct in utero administration (E14), sustained and strong expression was
      observed 4 months into adulthood. Quantification of transduction and viral copy
      number was comparable when using non-integrating lentivirus and conventional
      integrating vector. These data support the use of non-integrating lentiviral
      vectors as an effective alternative to their integrating counterparts in gene
      therapy applications, and highlight their potential for treatment of inherited
      and acquired neurological disorders.

PMID- 19158848
TI  - [Danger for life and health].

PMID- 19158849
TI  - [Cannabis--a drug of abuse and a therapeutic agent?].

PMID- 19158850
TI  - Fast dynamic waveguides and waveguide arrays in photorefractive Sn(2)P(2)S(6)
      induced by visible light.
AB  - We report on dynamic waveguides and waveguide arrays induced beneath the surface
      of electro-optic Sn(2)P(2)S(6) crystals by visible light at 514 nm. The waveguide
      structures are generated by interband photoexcitation and drift or diffusion
      charge transport mechanism. These structures are probed nondestructively in the
      transverse direction with a beam at a longer wavelength. We measured the fastest
      formation of light induced waveguides in the visible up to now. The recording
      times are below 200 mus for intensities above 0.1 W/cm2. By interfering two light
      beams, dynamic waveguide arrays are generated with waveguide spacings of 7
      microm. If an electric field is applied to the crystal, these arrays can be
      spatially shifted by 1.5 mum for an applied field of E(0) = 1 kV/cm.

PMID- 19158851
TI  - Coherent beam combining with double stochastic approximation based on logic
      comparison algorithm.
AB  - We introduce a novel algorithm used in coherent beam combining: double stochastic
      approximation based on logic comparison (DSAL). Both the theoretical
      investigation and the numerical simulation indicated that the DSAL method can be
      convergent efficiently. The coherent beam combining of two W-level fiber
      amplifiers experiment shows that the whole system in close-loop performs well for
      long-time observation and nearly 72% combining efficiency was realized. In the
      further experiment with some improvement, the combining efficiency increased to
      81%. This algorithm has widely potential application in coherent beam combining
      field.

PMID- 19158852
TI  - Single-mode Er-doped fiber random laser with distributed Bragg grating feedback.
AB  - We report the implementation of a one-dimensional random laser based on an Er/Ge
      co-doped single-mode fiber with randomly spaced Bragg gratings. The random
      grating array forms a complex cavity with high quality factor resonances in the
      range of gain wavelengths centered around 1535.5 nm. The reflection spectra of
      the grating array and the emission spectra of the laser are investigated for
      different numbers of gratings. The experimental results are compared
      qualitatively with numerical simulations of the light propagation in one
      dimensional Bragg grating arrays based on a transfer matrix method. The system is
      pumped at 980 nm and the experimentally observed output radiation presents a
      typical laser threshold behavior as a function of the pump power. We find that
      the laser output contains several competing spectral modes.

PMID- 19158853
TI  - Origin of the bound states of pulses in the stretched-pulse fiber laser.
AB  - A simple analytical model of the mechanism responsible for the formation of bound
      states of pulses in the stretched-pulse fiber laser is given. The proposed model
      is based on a noncoherent interaction occurring between the pulses near their
      position of maximum stretch within the dispersion-managed cavity, where the
      pulses possess a large linear chirp. This nonlinear interaction is due to the
      combined effects of the cross-phase modulation and the cross-amplitude modulation
      caused by the nonlinear gain associated with the mode-locking mechanism used in
      the laser. This model predicts the existence of a single bound state with a
      separation of the order of the pulsewidth at maximum stretch, a result consistent
      with simulations and experiments.

PMID- 19158854
TI  - Evaluation of femtosecond laser-induced breakdown spectroscopy for explosive
      residue detection.
AB  - Recently laser-induced breakdown spectroscopy (LIBS) has been investigated as a
      potential technique for trace explosive detection. Typically LIBS is performed
      using nanosecond laser pulses. For this work, we have investigated the use of
      femtosecond laser pulses for explosive residue detection at two different
      fluences. Femtosecond laser pulses have previously been shown to provide several
      advantages for laser ablation and other LIBS applications. We have collected LIBS
      spectra of several bulk explosives and explosive residues at different pulse
      durations and energies. In contrast to previous femtosecond LIBS spectra of
      explosives, we have observed atomic emission peaks for the constituent elements
      of explosives - carbon, hydrogen, nitrogen, and oxygen. Preliminary results
      indicate that several advantages attributed to femtosecond pulses are not
      realized at higher laser fluences.

PMID- 19158855
TI  - Theoretical analysis on the tuning dynamics of the waveguide-grating structures.
AB  - We investigate theoretically the tuning properties of the resonant mode of the
      waveguide-grating structures (WGS). This intends to understand how tuning
      mechanisms of the waveguide resonance mode depend on the structural and the
      geometric parameters of the WGS device, which can be used as guidance for the
      design of biosensors and other optoelectronic devices. The device parameters
      studied here include the angle of incidence, the thickness and refractive index
      of the waveguide, the period of the grating, and the refractive indices of the
      substrate and the medium on top of the grating. In particular, the control of the
      tuning rate and the adjustment of the tuning range by optimizing the combination
      of the relevant parameters provide a practical route for the design of biosensor
      and optical switch.

PMID- 19158856
TI  - Generation of tuneable 589nm radiation as a Na guide star source using an optical
      parametric amplifier.
AB  - We describe a 5.5W 589 nm source based on a passively mode-locked Nd:YVO4 laser
      and a multi-stage Lithium Triborate optical parametric amplifier seeded by a
      tuneable semiconductor laser. We show this system can produce rapidly tuneable,
      transform-limited pulses in near diffraction-limited beams at 589 nm, useful for
      Na guide star applications. The attraction of this scheme is that it can be
      assembled from commercially available hardware and is readily scalable to high
      average powers.

PMID- 19158857
TI  - High-power Yb-doped photonic bandgap fiber amplifier at 1150-1200 nm.
AB  - Ytterbium-doped solid-core photonic bandgap fiber amplifiers operating at the
      long-wavelength edge of the ytterbium gain band are reported. The low-loss
      bandgap transmission window is formed in the very low gain region, whilst outside
      the bandgap, large attenuation inhibits the exponential growth of amplified
      spontaneous emission in the huge-gain 1030-1100 nm region. Hence parasitic-lasing
      free, high-power amplification with a marked efficiency is enabled. A 32 W output
      at 1156 nm with a 66% slope efficiency and 30 W output at 1178 nm with a 58%
      slope efficiency were successfully obtained. To our knowledge, these are the
      highest output powers generating from active photonic bandgap fibers, as well as
      from ytterbium-doped fiber lasers at these wavelengths.

PMID- 19158858
TI  - Dissipative vector solitons in a dispersionmanaged cavity fiber laser with net
      positive cavity dispersion.
AB  - We report on the experimental observation of gain-guided vector solitons (GGVSs)
      in a dispersion-managed fiber laser mode-locked with a semiconductor saturable
      absorber mirror (SESAM). Both the frequency-locked and phase-locked GGVS were
      observed. In addition, formation of multiple GGVSs and GGVS harmonic mode-locking
      were also experimentally revealed. Numerical simulations confirmed the GGVS
      formation in the fiber lasers.

PMID- 19158859
TI  - First-order loss-less differentiators using long period gratings made in Er-doped
      fibers.
AB  - An active-fiber-based all-optical first-order temporal differentiator with power
      efficiency surpassing 100% is demonstrated experimentally. It is based on a long
      period fiber grating (LPFG) inscribed into a piece of highly-doped Erbium-doped
      fiber (EDF). The performed theoretical analysis considers effects like relative
      position of the LPFG with respect to the input end of the EDF and influence of
      the input signal power. In the design, parameters like noise characteristics and
      level of non-linear interaction are taken into account. The advantages of such an
      implementation over the setup using concatenation of a passive LPFG with an
      amplifier lies in reducing the unwanted nonlinearities and reducing the amplified
      spontaneous emission (ASE).

PMID- 19158860
TI  - Skyless polarimetric calibration and visibility enhancement.
AB  - Outdoor imaging in haze is plagued by poor visibility. A major problem is
      spatially-varying reduction of contrast by airlight, which is scattered by the
      haze particles towards the camera. However, images can be compensated for haze,
      and even yield a depth map of the scene. A key step in such scene recovery is
      subtraction of the airlight. In particular, this can be achieved by analyzing
      polarization-filtered images. This analysis requires parameters of the airlight,
      particularly its degree of polarization (DOP). These parameters were estimated in
      past studies by measuring pixels in sky areas. However, the sky is often unseen
      in the field of view. This paper derives several methods for estimating these
      parameters, when the sky is not in view. The methods are based on minor prior
      knowledge about a couple of scene points. Moreover, we propose blind estimation
      of the DOP, based on the image data. This estimation is based on independent
      component analysis (ICA). The methods were demonstrated in field experiments.

PMID- 19158861
TI  - Optically adjustable light filaments generated by a compact laser convertor.
AB  - In the paper, the geometrical parameters and energetics of the extremely narrow
      pseudo-nondiffracting beams with the spot size of several micrometers are
      examined. The main attention is focused on design, realization and testing of the
      set-up enabling conversion of the laser diode beam or the fiber mode to the
      narrow Bessel-Gauss beam whose spot can be continuously relocated across the
      plane perpendicular to the beam propagation direction. Application of the laser
      convertor to the optical manipulation is demonstrated on experiments enabling
      transport of microparticles along a desired trajectory.

PMID- 19158862
TI  - Skin autofluorescence for the risk assessment of chronic complications in
      diabetes: a broad excitation range is sufficient.
AB  - Skin autofluorescence (AF) is becoming an accepted clinical method for assessing
      the risk of chronic complications in diabetes mellitus (DM). In this study, the
      role of the excitation wavelength in the recognition of increased risk of
      diabetes-related chronic complications was investigated. An Excitation Emission
      Matrix Scanner (EEMS) was used to perform noninvasive measurements in four age
      matched groups of patients with type 1 and type 2 DM, with and without chronic
      complications, as well as in a control group (N=97 in total). AF was calculated
      for excitation wavelengths in the range 355 - 405 nm. Mean spectra were assessed
      per group. AF values in both type 1 and type 2 DM patients with complications
      were increased compared to the control subjects (p < 0:01); this ratio remained
      practically constant, independent of the excitation wavelength. No emission peaks
      were distinctive for specific patient groups. We conclude that in these groups,
      no characteristic fluorophores dictate the use of a specific wavelength or set of
      wavelengths. The results show the validity of applying a broad excitation
      wavelength range for risk assessment of chronic complications in diabetes.

PMID- 19158863
TI  - Ambient-stable blue luminescent silicon nanocrystals prepared by nanosecond
      pulsed laser ablation in water.
AB  - Even with intensive research, air-stable blue light emission from silicon
      nanocrystals (Si-ncs) at room temperature still remains a challenge. We show that
      stable and blue-luminescent Si-ncs can be produced by laser-generated plasma
      (nanosecond-pulsed excimer laser) confined in water. These Si-ncs exhibit quantum
      confinement effect due to their size and are produced with an environmentally
      compatible process. The effect of aging for several weeks in water and air on
      blue Si-ncs emission properties is compared. The oxide shell around the
      nanocrystalline core formed during laser processing in water offers the required
      conditions for the confinement of excitons that allow for stable (in either air
      or water) blue photoluminescence at room temperature.

PMID- 19158864
TI  - Closed-form algorithms for phase retrieval with an additive point signal.
AB  - The phase retrieval problem is a problem of a reconstruction of a signal from the
      magnitude of its Fourier transform. In this paper, we consider the problem of
      reconstructing an unknown one-dimensional signal from the magnitude of its
      Fourier transform and the magnitude of the Fourier transform of another signal
      that is made by the addition of a point signal at the center of the original
      signal. After we show that there are exactly two solution signals that satisfy
      the given condition, we develop a closed-form algorithm that may reconstruct the
      two solution signals.

PMID- 19158865
TI  - Isolated sub-100-as pulse generation by optimizing two-color laser fields using
      simulated annealing algorithm.
AB  - We propose a method to broaden the cut-off region of high harmonic generation by
      optimizing the parameters of two-color laser fields synthesized by an intense 5
      fs pulse at 800 nm and a relatively weak, subharmonic pulse at 2400 nm. Simulated
      Annealing (SA) algorithm is employed to optimize the electric field amplitude,
      pulse duration of the control pulse, and the time delay between two pulses. Our
      simulation shows that a broadened XUV supercontinuum with a 115 eV spectral width
      can be generated, which is two times broader compared with no optimization, and
      directly creates an isolated 76as pulse even without any phase compensation.

PMID- 19158866
TI  - Extraordinary low transmission effects for ultra-thin patterned metal films.
AB  - Thin metal films show a residual transmission for light in the visible and UV
      spectral range. This transmission can be strongly reduced by an appropriate sub
      wavelength patterning of the metal film. Our investigation is focused on metal
      films with a thickness much below 100nm, where the transmission response is
      dominated by the individual posts acting like antennas and cannot be attributed
      to the excitation of surface plasmons. The almost complete suppression of
      transmission for ultra-thin metal films depends mainly on the absorber width, but
      not on the pitch of the pattern. The effect is robust with respect to
      imperfections of the geometry or larger features imprinted into the sub
      wavelength pattern.

PMID- 19158867
TI  - Light localization induced enhancement of third order nonlinearities in a GaAs
      photonic crystal waveguide.
AB  - Nonlinear propagation experiments in GaAs photonic crystal waveguides (PCW) were
      performed, which exhibit a large enhancement of third order nonlinearities, due
      to light propagation in a slow mode regime, such as two-photon absorption (TPA),
      optical Kerr effect and refractive index changes due to free-carriers generated
      by TPA. A theoretical model has been established that shows a very good
      quantitative agreement with experimental data and demonstrates the important role
      that the group velocity plays. These observations give a strong insight into the
      use of PCWs for optical switching devices.

PMID- 19158868
TI  - Testing ultrafast mode-locking at microhertz relative optical linewidth.
AB  - We report new limits on the phase coherence of the ultrafast mode-locking process
      in an octave-spanning Ti:sapphire comb.We find that the mode-locking mechanism
      correlates optical phase across a full optical octave with less than 2.5 microHZ
      relative linewidth. This result is at least two orders of magnitude below recent
      predictions for quantum-limited individual comb-mode linewidths, verifying that
      the mode-locking mechanism strongly correlates quantum noise across the comb
      spectrum.

PMID- 19158869
TI  - Synchronously pumped continuous-wave mode-locked yellow Raman laser at 559 nm.
AB  - We demonstrate the operation of a continuous-wave (CW) picosecond yellow laser
      operating at 559 nm. A solid-state Raman laser using a KGW crystal was
      synchronously pumped by an 80 MHz laser operating at 532 nm. The output pulses
      were compressed from 10 ps at 532 nm down to 3.2 ps at 559 nm, strongly depending
      on the cavity length detuning. Slope efficiencies up to 42% were observed when
      the system was optimized for maximum output power. This technique can be extended
      to a range of visible wavelengths between 550-600 nm by using different Raman
      materials, and by cascaded conversion.

PMID- 19158870
TI  - Extended filamentation with temporally chirped femtosecond Bessel-Gauss beams in
      air.
AB  - We report experimental results on ultrafast filamentation with temporally chirped
      femtosecond Bessel-Gauss beams. We find that by chirping the pulses, the
      longitudinal range of the generated plasma channels can be extended relative to
      filaments generated by fully compressed, transform-limited femtosecond pulses. We
      find a clear correlation between the extent of filamentation and the intensity of
      the on-axis emission by the femtosecond Bessel-Gauss beam. The on-axis emission
      is negligible for fully compressed pulses, but it can become quite substantial
      (up to 10% of the input pulse energy) when chirped pulses are used. Under certain
      conditions, the on-axis emission becomes sufficient for generating its own plasma
      channel thus resulting in extended filamentation. This effect may offer means of
      remote control over filament formation with femtosecond Bessel-Gauss beams.We
      identify a four-wave mixing process, enhancement of which is likely to result in
      a maximum of the on-axis emission, and derive a simple expression for estimating
      the duration of the chirped pulse that is required for such enhancement. Our
      estimations are in good agreement with the experiment.

PMID- 19158871
TI  - Numerical study on self-similar pulses in mode-locking fiber laser by coupled
      Ginzburg-Landau equation model.
AB  - A theoretical model is established to study the self-similar pulses in nonlinear
      polarization evolution (NPE) mode-locked fiber lasers. The propagation of pulse
      in single mode fibers and gain fibers are described by coupled Ginzburg- Landau
      equation (GLE). Two wave plates and a polarizer are considered to realize the NPE
      mechanism in simulation. This model describes the laser completely and provides
      some useful pulses' information. In our simulation the laser generates high
      quality self-similar pulses output. The region of steady self-similar pulses
      operation is found. The polarization states of different parts across the pulse
      are simulated along the laser cavity. It is found that polarization states across
      the pulse are modulated from elliptical to almost circular before the pulse
      passing through the polarizer.

PMID- 19158872
TI  - Tuning and focusing THz pulses by shaping the pump laser beam profile in a
      nonlinear crystal.
AB  - Spatially shaped femtosecond laser pulses are used to generate and to focus
      tunable terahertz (THz) pulses by Optical Rectification in a Zinc Telluride
      (ZnTe) crystal. It is shown analytically and experimentally that the focusing
      position and spectrum of the emitted THz pulse can be changed, in the
      intermediate field zone, by controlling the spatial shape of the near-infrared
      (NIR) femtosecond (fs) laser pump. In particular, if the pump consists of
      concentric circles, the emitted THz radiation is confined around the propagation
      axis, producing a THz pulse train, and focusing position and spectrum can be
      controlled by changing the number of circles and their diameter.

PMID- 19158873
TI  - Polarization dependent devices realized by using asymmetrical hole array on a
      metallic film.
AB  - A method is brought forward for realizing polarization dependent devices by
      employing sub-wavelength asymmetrical hole array on a metallic film. Based on the
      fundamental mode approximation, the phase retardations of rectangular hole for
      two orthogonal polarization incident waves are analyzed and calculated. Using
      rectangular hole array, a bifocal-polarization lens for the infrared radiation
      with 10.6 microm wavelength is designed. Its focal lengths for x- and y-
      polarized incident wave are examined by the finite difference time domain (FDTD)
      method and the Rayleigh-Sommerfeld diffraction integrals and the obtained results
      agree well with the designed values.

PMID- 19158874
TI  - Maximizing Young's fringe visibility under unitary transformations for mean
      square coherent light.
AB  - Given the values of the degree of polarization of the fields at the pinholes in a
      Young interferometer, the maximum attainable visibility under unitary
      transformations is determined when the illuminating beam is mean-square light.
      Analytical expressions are also obtained for both the field vector (in the mean
      square sense) and the cross-spectral density matrix associated with this kind of
      beams. A comparative summary is also provided of the main characteristics of well
      known types of random electromagnetic fields frequently handled in the
      literature.

PMID- 19158875
TI  - The empirical mode decomposition: a must-have tool in speckle interferometry?
AB  - In a wider and wider range of research and engineering activities, there is a
      growing interest for full-field techniques, featuring nanometric sensitivities,
      and able to be addressed to dynamic behaviors characterization. Speckle
      interferometry (SI) techniques are acknowledged as good candidates to tackle this
      challenge. To get rid of the intrinsic correlation length limitation and simplify
      the un-wrapping step, a straightforward approach lies in the pixel history
      analysis. The need of increasing performances in terms of accuracy and
      computation speed is permanently demanding new efficient processing techniques.
      We propose in this paper a fast implementation of the Empirical Mode
      Decomposition (EMD) to put the SI pixel signal in an appropriate shape for
      accurate phase computation. As one of the best way to perform it, the analytic
      method based on the Hilbert transform (HT) of the so-transformed signal will then
      be reviewed. For short evaluation, a zero-crossing technique which exploits
      directly the extrema finding step of the EMD will be presented. We propose
      moreover a technique to discard the under-modulated pixels which yield wrong
      phase evaluation. This work is actually an attempt to elaborate a phase
      extraction procedure which exploits all the reliable information in 3D, - two
      space and one time coordinates -, to endeavor to make the most of SI raw data.

PMID- 19158876
TI  - Optical wavefront measurement using phase retrieval with transverse translation
      diversity.
AB  - We demonstrate the use of transverse translation-diverse phase retrieval as a
      method for the measurement of wavefronts in situations where the detected
      intensity patterns would be otherwise undersampled. This technique involves using
      a smaller moving subaperture to produce a number of adequately sampled intensity
      patterns. The wavefront is then retrieved using an optimization jointly
      constrained by them. Expressions for the gradient of an error metric with respect
      to the optimization parameters are given. An experimental arrangement used to
      measure the transmitted wavefront of a plano-convex singlet using this technique
      is described. The results of these measurements were repeatable to within
      approximately lambda/100 RMS.

PMID- 19158877
TI  - Photonic band-edge micro lasers with quantum dot gain.
AB  - We demonstrate optically pumped continuous-wave photonic band-edge microlasers on
      a two-dimensional photonic crystal slab. Lasing was observed at a photonic band
      edge, where the group velocity was significantly small near the K point of the
      band structure having a triangular lattice. Lasing was achieved by using a
      quantum dot gain material, which resulted in a significant decrease in the laser
      threshold, compared with photonic band-edge lasers using quantum well gain
      material. Extremely low laser thresholds of approximately 80 nW at 6 K was
      achieved. Lasing was observed in a defect-free photonic crystal as small as
      approximately 7 microm square.

PMID- 19158878
TI  - Tree array quantum cascade laser.
AB  - A monolithic coupling scheme for mid-infrared quantum cascade laser arrays is
      investigated with respect to brightness enhancement. The tree-shaped resonator
      enables parallel coupling of six laser elements into a single element by means of
      several Y-junctions. Phase-locking is observed on the basis of far field
      analysis, and leads to in-phase emission on both sides of the device. The
      experimental results match calculated far field profiles and demonstrate a high
      level of modal control when driven far above threshold. Whereas optical power
      measurements confirm negligible coupling losses, the slope efficiency is below
      the theoretically expected value, which is attributed to modal competition.
      Additional evaluation of near fields and spectral characteristics provides
      background on the modal dynamics of the sophisticated cavity and reveals
      limitations to coherent beam combining. The findings pave the way to improved
      coupling efficiency and brightness scaling of a single facet emitting compact
      quantum cascade laser array.

PMID- 19158879
TI  - Correlation between photorefractive index changes and optical damage thresholds
      in z-cut proton-exchanged-LiNbO(3) waveguides.
AB  - An interferometric Mach-Zehnder technique very recently developed has been
      applied to measure photorefractive index changes in different types of z-cut
      proton-exchanged planar waveguides in LiNbO(3). These measurements are
      complemented by determining the intensitythreshold for the onset of optical
      damage with a standard single-beam setup. In the intensity region just below the
      threshold-intensity obtained in the single-beam experiment the refractive index
      change is found to saturate at values around1x10(-4). Furthermore, we measure the
      dark conductivities of proton-exchanged waveguides by monitoring the decay of the
      light-induced index changes. Via the time constant of the decay we obtain dark
      conductivities of the order of about 5x10(-16) Omega (-1) cm (-1), that are
      negligible compared with the photoconductivity within the light intensity range
      used. The results of the measurements compare well with the predictions of a
      recent work, that uses a two-center model to explain the optical damage.

PMID- 19158880
TI  - Loss mechanisms in mid-infrared extraordinary optical transmission gratings.
AB  - The optical properties of periodic arrays of subwavelength apertures in metal
      films on GaAs substrates are studied. Specifically, geometric and material losses
      for these plasmonic structures are characterized using angular dependent
      transmission, normal incidence reflection, and angular dependent diffraction
      experiments, in addition to a crossed-polarizer transmission experiment. The
      optical properties of the samples as a function of engineered material losses are
      studied. Using this comprehensive approach to the characterization of the
      plasmonic structures, we are able to identify and isolate specific loss
      mechanisms, as well as identify the effect of free carriers on the optical
      properties of the structures.

PMID- 19158881
TI  - Floating dielectric slab optical interconnection between metal-dielectric
      interface surface plasmon polariton waveguides.
AB  - A simple and effective optical interconnection which connects two distanced
      single metal-dielectric interface surface plasmon waveguides by a floating
      dielectric slab waveguide (slab bridge) is proposed. Transmission characteristics
      of the suggested structure are numerically studied using rigorous coupled wave
      analysis, and design rules based on the study are given. In the wave-guiding
      part, if the slab bridge can support more than the fundamental mode, then the
      transmission efficiency of the interconnection shows strong periodic dependency
      on the length of the bridge, due to the multi-mode interference (MMI) effect.
      Otherwise, only small fluctuation occurs due to the Fabry-Perot effect. In
      addition, light beating happens when the slab bridge is relatively short. In the
      wave-coupling part, on the other hand, gap-assisted transmission occurs at each
      overlapping region as a consequence of mode hybridization. Periodic dependency on
      the length of the overlap region also appears due to the MMI effect. According to
      these results, we propose design principles for achieving both high transmission
      efficiency and stability with respect to the variation of the interconnection
      distance, and we show how to obtain the transmission efficiency of 68.3% for the
      1mm-long interconnection.

PMID- 19158882
TI  - Mechanism of the large polarization rotation effect in the all-dielectric
      artificially chiral nanogratings.
AB  - The physical mechanism of the large polarization rotation effect in direct
      transmission of the all-dielectric artificially chiral nanogratings is explored
      by experiment and numerical analysis. It is shown that the different coupling of
      right- and left-circularly polarized components of the normally incident light to
      the leaky guided modes or Fabry-Perot resonance modes lead to the enhanced
      circular dichroism, resulting in the giant polarization rotation effect. The mode
      profile and local field calculations demonstrate intuitive images of the
      different coupling performance at resonances.

PMID- 19158883
TI  - Sub-dB/cm propagation loss in silver stripe waveguides.
AB  - We demonstrate sub-dB/cm propagation losses in polymer-based silver stripe
      waveguides at the wavelength of 1.31 microm. The silver stripe waveguides were
      fabricated in a low-loss fluorinated polymer clad. To form uniform metal stripe
      patterns, which are essential for reducing propagation loss, we developed a lift
      off process using double layers of photoresist and SiNx. A propagation loss of
      less than 1.0 dB/cm was obtained with the 11- nm-thick silver stripes in the
      width range of 1.5 - 4.5 microm. A coupling loss of approximately 1.0 dB with a
      polarization maintaining single mode fiber was achieved for a width of 4.5
      microm. For a width of 2.0 microm, we recorded a minimum propagation loss of 0.4
      dB/cm, which is comparable with that of dielectric multi-mode waveguides.

PMID- 19158884
TI  - Decision-aided maximum likelihood detection in coherent optical phase-shift
      keying system.
AB  - A novel decision-aided maximum likelihood (DA ML) technique is proposed to
      estimate the carrier phase in coherent optical phase-shift-keying system. The DA
      ML scheme is a totally linear computational algorithm which is feasible for on
      line processing in the real systems. The simulation results show that the DA ML
      receiver can outperform the conventional Mth power scheme, especially when the
      nonlinear phase noise is dominant.

PMID- 19158885
TI  - Bidirectional photoresponse of surface pretreated azobenzene liquid crystal
      polymer networks.
AB  - We report on the photodriven, polarization-controlled response of UV-pretreated
      azobenzene-based liquid crystal polymer networks (azo- LCN) of polydomain
      orientation to higher wavelength CW argon-ion laser light (Ar(+)) of 457-514 nm.
      The significant absorbance of the azo-LCN cantilever in the UV is used to form an
      approximately 1 microm thick cis-isomer rich skin. Subsequent exposure to the
      Ar(+) laser drives a bidirectional bending process that is the result of two
      distinguishable photochemical processes. First, 457-514 nm laser light
      (regardless of polarization state) drives cis-trans photoisomerization of the UV
      pretreated surface, restoring the order of the azobenzene liquid crystalline
      moieties. Mechanically, the cis-trans process results in an expansion on the
      exposed surface that forces the cantilever to undergo a rapid bend away from the
      laser source. Once a sufficient number of trans-azobenzene moieties are
      regenerated, continued Ar(+) illumination promotes both the trans-cis and cis
      trans processes enabling trans-cis-trans reorientation. In this particular system
      and conditions, trans-cis-trans reorientation enables polarization controlled
      mechanical bending of different angles towards the Ar(+) source. Photomechanical
      responses of UV-pretreated azo-LCN demonstrate the viability of photogenerated
      effects in UV-rich environments such as space.

PMID- 19158886
TI  - An iterative model of diffuse illumination from bidirectional photometric data.
AB  - This paper presents a methodology for including the photometric raw data sets
      into the diffuse illumination design process. The method is based on computing
      the luminance distribution on the outgoing side of diffusing elements from
      measured bidirectional scattering distribution functions (BSDFs). The model is
      limited to specimens that create rotationally symmetric scattering distribution.
      The calculation procedure includes the linear superposition and the correcting
      feedback. As an application example, the method is verified by a commercially
      available diffusing sheet illuminated by a 32-inch backlighting module. Close
      agreement (correlation coefficient = 98.6%) with the experimental measurement
      confirmed the validity of the proposed procedure.

PMID- 19158887
TI  - Interval type-II fuzzy anisotropic diffusion algorithm for speckle noise
      reduction in optical coherence tomography images.
AB  - A novel speckle noise reduction algorithm based on a combination of Anisotropic
      Diffusion (AD) filtering and Interval Type-II fuzzy system was developed for
      reducing speckle noise in Optical Coherence Tomography (OCT) images. Unlike
      regular AD, the Interval Type-II fuzzy based AD algorithm considers the
      uncertainty in the calculated diffusion coefficient and appropriate adjustments
      to the coefficient are made. The new algorithm offers flexibility in optimizing
      the trade-off between the two image metrics: signal-to-noise (SNR) and Edginess,
      which are directly related to the structure of the imaged object. Application of
      the Interval Type-II fuzzy AD algorithm to OCT tomograms acquired in-vivo from a
      human finger tip and human retina show reduction in the speckle noise with very
      little edge blurring and about 13 dB and 7 dB image SNR improvement respectively.
      Comparison with Wiener, Adaptive Lee and regular Anisotropic Diffusion filters,
      applied to the same images, demonstrates the superior performance of the fuzzy
      Type-II AD algorithm in terms image SNR and edge preservation metrics
      improvement.

PMID- 19158888
TI  - Influence of imperfections on the insulating and guiding properties of finite Si
      inverted opal crystals.
AB  - The stability of the photonic properties of Si-infiltrated opals for fabrication
      disorder is tested with following models of applied imperfections: deviations in
      radii of spheres, deviations in spheres positions and both of them. The
      deviations are assumed to be distributed accordingly to the normal law and to the
      skewed distribution experimentally observed in the process of production of
      polymer self-assembled crystals. The criteria for the photonic crystals
      tolerances are evaluated versus the quality of photonic insulation provided by
      films or bulk spheres of finite thicknesses. In addition the stability of the
      photonic crystal waveguides in inverted opals is tested versus the imperfections
      strength.

PMID- 19158889
TI  - Extraordinary transmission through metal-coated monolayers of microspheres.
AB  - The spectral dependence of the extraordinary transmission through monolayers of
      close-packed silica or polystyrene microspheres on a quartz support, covered with
      different thin metal films (Ag, Au and Ni) was investigated. The measured spectra
      were compared with modeled transmission spectra using finite difference time
      domain (FDTD) calculations. Measured and modeled spectra show good overall
      agreement. The supported modes in the sphere array were found to be of utmost
      importance for the transmission mechanism and the results also suggest that the
      presence of guided modes in the photonic crystal may further enhance the
      extraordinary transmission through the metal film.

PMID- 19158890
TI  - Metamaterials for THz polarimetric devices.
AB  - We present experimental and numerical investigations of planar terahertz
      metamaterial structures designed to interact with the state of polarization. The
      dependence of metamaterial resonances on polarization results in unique amplitude
      and phase characteristics of the terahertz transmission, providing the basis for
      polarimetric terahertz devices. We highlight some potential applications for
      polarimetric devices and present simulations of a terahertz quarter-wave plate
      and a polarizing terahertz beam splitter. Although this work was performed at
      terahertz frequencies, it may find applications in other frequency ranges as
      well.

PMID- 19158892
TI  - Zero-broadening measurement in Brillouin based slow-light delays.
AB  - A novel method for the achievement of zero-broadening in a SBS based slow-light
      system is discussed in theory and demonstrated experimentally. The system is
      realized just with a single broadened Brillouin gain. It is shown, that if the
      gain bandwidth is much broader than the initial pulse width, the output pulse
      width decreases with increasing pump power. A compression of approximately 90 %
      of the initial pulse width was achieved in simulation and experiment.

PMID- 19158891
TI  - Three-dimensional endomicroscopy of the human colon using optical coherence
      tomography.
AB  - Three-dimensional (3D) endomicroscopy imaging of the human gastrointestinal tract
      is demonstrated in vivo using a swept source optical coherence tomography (OCT)
      system. 3D datasets of normal and pathologic regions of the colon, rectum, and
      anal verge were obtained from seven volunteers undergoing diagnostic or
      therapeutic colonoscopy. 3D-OCT enables high resolution endomicroscopy
      examination through visualization of tissue architectural morphology using
      virtual cross-sectional images with arbitrary orientations as well as en face
      projection images. Axial image resolutions of 6 mum in tissue are obtained over a
      approximately 180 mm2 field with an imaging range of 1.6 mm. A Fourier domain
      mode locked (FDML) laser providing a tuning range of 180 nm at a sweep rate of 62
      kHz is used as the system light source. This clinical pilot study demonstrates
      the potential of 3D-OCT for distinguishing normal from pathologic colorectal
      tissue, assessing endoscopic therapies and healing progression.

PMID- 19158894
TI  - Optical limiting properties of nonlinear multimode waveguide arrays.
AB  - An experimental investigation of the transmission of multimode capillary
      waveguide arrays containing a liquid nonlinear absorber shows an enhanced
      nonlinear response relative to that found in a single waveguide and to the same
      length of bulk material. Comparison of the nonlinear response of arrays with
      different pitch to diameter (d/Lambda) ratios confirm that both the intensity
      distribution within an individual waveguide and coupling between the elements of
      the array influence the overall nonlinear response.

PMID- 19158895
TI  - All-solid-state parametric Raman anti-Stokes laser at 508 nm.
AB  - We report a parametric anti-Stokes Raman laser using potassium gadolinium
      tungstate, generating output chiefly at the first anti-Stokes at 508 nm. The
      compact 4.5 cm long device is pumped by a Q-switched 532 nm laser and uses an off
      axis Stokes resonator to provide non-collinear phase matching between the pump
      and the generated Stokes and anti-Stokes fields. Anti-Stokes output energies up
      0.27 mJ were obtained at a conversion efficiency from the pump of 0.46%. Second-
      and third-order anti-Stokes lines at 486 nm and 465 nm were also observed.

PMID- 19158896
TI  - Polarization-independent active metamaterial for high-frequency terahertz
      modulation.
AB  - We present a polarization-independent metamaterial design for the construction of
      electrically tunable terahertz (THz) devices. The implemented structure consists
      of an array of gold crosses fabricated on top of an n-doped gallium arsenide
      (GaAs) layer. Utilizing THz time-domain spectroscopy, we show that the electric
      resonance and thus the transmission properties of the cross structure can be
      tuned by an externally applied bias voltage. We further demonstrate the fast
      amplitude modulation of a propagating THz wave for modulation frequencies up to
      100 kHz.

PMID- 19158898
TI  - Fast associative filtering based on two-dimensional discrete Walsh transform by a
      volume holographic correlator.
AB  - An optical fast associative filtering method based on a multi-channel volume
      holographic correlator to search the database as a front-end filter is described.
      The features of searching query are parallelly extracted by a volume holographic
      correlator based on two-dimensional discrete Walsh transform, and are used to
      measure the similarity between the query and all the database records. The best
      matches are picked up for further searching. An experiment is carried out, and
      the experimental results prove the validity of the method.

PMID- 19158897
TI  - Picometer level displacement metrology with digitally enhanced heterodyne
      interferometry.
AB  - Digitally enhanced heterodyne interferometry is a laser metrology technique
      employing pseudo-random codes phase modulated onto an optical carrier. We present
      the first characterization of the technique's displacement sensitivity. The
      displacement of an optical cavity was measured using digitally enhanced
      heterodyne interferometry and compared to a simultaneous readout based on
      conventional Pound-Drever-Hall locking. The techniques agreed to within 5 pm/
      radicalHz at 1 Hz, providing an upper bound to the displacement noise of
      digitally enhanced heterodyne interferometry. These measurements employed a real
      time signal extraction system implemented on a field programmable gate array,
      suitable for closed-loop control applications. We discuss the applicability of
      digitally enhanced heterodyne interferometry for lock acquisition of advanced
      gravitational wave detectors.

PMID- 19158899
TI  - Effect of saturation on the diffraction efficiency of holographically recorded
      gratings in azopolymer films.
AB  - The diffraction efficiency of phase gratings recorded by two s-polarized waves in
      a polymer is modeled. The molecular orientation distribution along the grating
      period is seen to become homogeneous as a function of time due to saturation.
      Experimental data is presented, in agreement with the model.

PMID- 19158900
TI  - Peak equalization of rational-harmonic-mode-locking fiberized semiconductor laser
      pulse via optical injection induced gain modulation.
AB  - Optical injection induced gain modulation of a semiconductor optical amplifier
      (SOA) is demonstrated to equalize the peak intensity of pulses generating from
      the rational-harmonic-mode-locking (RHML) SOA based fiberized semiconductor
      laser. This is achieved by adjusting the temporal shape of the injected optical
      signal generated from a Mach-Zehnder intensity modulator, in which the DC biased
      level exceeding Vpi and the electrical pulse amplitude of 1.5Vpi are concurrently
      employed. Numerical simulation on the injected optical signal profile and the SOA
      gain during the inverse-optical-pulse injection induced gain modulation process
      are also demonstrated. After a peculiar inverse-optical-pulse injection, each
      pulse in the 5th-order RHML pulse-train experiences different gain from
      temporally varied SOA gain profile, leading the pulse peak to equalize one
      another with a minimum standard deviation of 2.5% on the peak intensity
      variation. The optimized 5th-order RHML pulse exhibits a signal-to-noise
      suppression ratio of 20 dB and a reduced variation on temporal spacing from 11 to
      4 ps. The clock amplitude jitter is compress from 35.3% to 7.3%, which is less
      than the limitation up to 10% for 5th order RHML generation.

PMID- 19158901
TI  - Empirical model of the photon path length for a single fiber reflectance
      spectroscopy device.
AB  - A reflectance spectroscopic device that utilizes a single fiber for both light
      delivery and collection has advantages over classical multi-fiber probes. This
      study presents a novel empirical relationship between the single fiber path
      length and the combined effect of both the absorption coefficient, mua (range:
      0.1-6 mm-1), and the reduced scattering coefficient, micro's (range: 0.3 - 10 mm
      1), for different anisotropy values (0.75 and 0.92), and is applicable to probes
      containing a wide range of fiber diameters (range: 200-2000 microm). The results
      indicate that the model is capable of accurately predicting the single fiber path
      length over a wide range (r = 0.995; range: 180-3940 microm) and predictions do
      not show bias as a function of either microa or micro's .

PMID- 19158902
TI  - Channel coding and time-diversity for optical wireless links.
AB  - Atmospheric turbulence can cause a significant performance degradation in free
      space optical communication systems. An efficient solution could be to exploit
      the temporal diversity to improve the performance of the transmission link.
      Depending on the tolerable delay latency, we can benefit from some degree of time
      diversity that we can exploit by employing channel coding and interleaving. In
      this paper, we investigate the efficiency of several channel coding techniques
      for different time diversity orders and turbulence conditions. We show that a
      simple convolutional code is a suitable choice in most cases as it makes a good
      compromise between decoding complexity and performance. We also study the
      receiver performance when the channel is estimated based on some training
      symbols.

PMID- 19158903
TI  - Generation of pseudo-Bessel beams at THz frequencies by use of binary axicons.
AB  - In order to miniaturize and integrate conveniently in THz quasi-optical systems,
      binary axicons, based on binary optical ideas, are introduced in our paper and
      designed for generating pseudo-Bessel beams at THz frequencies. The designed
      binary axicons are easier to fabricate than holographic axicons, more compact and
      thus less lossy in the material when compared with classical cone axicons. To
      calculate the electromagnetic fields diffracted by binary axicons precisely, a
      two-dimension finite-difference time-domain (2-D FDTD) method in conjunction with
      Stratton- Chu formulas are employed in this paper. Applying this method, the
      properties of pseudo-Bessel beams produced by binary axicons are analyzed, and a
      brief summary is given in the end.

PMID- 19158904
TI  - A non-contact method and instrumentation to monitor renal ischemia and
      reperfusion with optical spectroscopy.
AB  - The potential of NADH autofluorescence as an in vivo intrinsic optical signature
      to monitor tissue metabolism is well recognized and supported by experimental
      results mainly in animal models. In this work, we propose a non-contact
      implementation of this method using large area excitation and employing a
      normalization method to account for non-metabolic signal changes. Proof of
      principle in vivo experiments were carried out using an autofluorescence imaging
      experimental system and a rat renal ischemia model. A hand-held fiber-optic probe
      was utilized to test the ability of the signal normalization method to address
      operational conditions associated with the translation of this method to a
      clinical setting. Preliminary pre-clinical in vivo test of the probe system was
      carried out using the same rat model.

PMID- 19158905
TI  - Modification of the Er3+ radiative lifetime from proximity to silicon
      nanoclusters in silicon-rich silicon oxide.
AB  - The lifetime of Er3+ in silicon-rich silicon oxide has been reported with quite
      widely varying values ranging from 9 ms to 2 ms. In this work, we consider the
      direct impact of silicon nanoclusters on the erbium radiative lifetime, and show
      that it is a function of the silicon nanocluster size, and also the erbium
      proximity to the nanocluster.

PMID- 19158906
TI  - Observation of dermal collagen fiber in wrinkled skin using polarization-resolved
      second-harmonic-generation microscopy.
AB  - Optical probe methods for in vivo assessments of cutaneous photoaging are
      necessary in fields such as anti-aging dermatology and skin cosmetic development.
      We investigated the relation between wrinkle direction and collagen orientation
      in ultraviolet-B-exposed (UVB-exposed) skin using polarization-resolved second
      harmonic-generation (SHG) microscopy. A polarization anisotropic image of the SHG
      light indicated that wrinkle direction in UVB-exposed skin is predominantly
      parallel to the orientation of dermal collagen fibers. Furthermore, collagen
      orientation in post-UVB-exposed skin with few wrinkles changed from that of UVB
      exposed wrinkled skin to that of no-UVB-exposed skin. The method proposed has the
      potential to become a powerful non-invasive tool for assessment of cutaneous
      photoaging.

PMID- 19158907
TI  - Plasmonic focusing with a coaxial structure illuminated by radially polarized
      light.
AB  - We propose and analyze a plasmonic lens that is illuminated by a radially
      polarized light. The lens is made of a coax-like geometry consisting of an
      annular dielectric slit surrounded by metal. Focusing efficiency is enhanced by
      the use of a circular grating assisting the coupling of light into surface
      plasmons. Further enhancement is obtained by introducing a circular Bragg grating
      on top of the structure, reflecting the surface plasmon modes that are
      propagating in the counter-focus direction. Using the Finite-Difference Time
      Domain approach we investigate the transmission and the focusing mechanisms, and
      study the effect of structural parameters on the performance of the plasmonic
      lens.

PMID- 19158908
TI  - Fast light in silicon ring resonator with resonance-splitting.
AB  - We report experimental demonstration of fast light in an over-coupled ultra
      compact silicon ring resonator with resonance-splitting. Strong mutual-coupling
      induced by the grating inside the ring leads to split resonances and accompanying
      large anomalous dispersion, thus providing a new approach to realizing fast light
      in the over-coupled region of the ring resonator. In the experiment, a maximum
      pulse advancement of 130 ps with low distortion is achieved for a 1-ns signal
      pulse in a 10-mum-radius silicon ring resonator. The observed pulse advancement
      agrees well with the theoretical calculation based on coupled mode theory.

PMID- 19158909
TI  - Active photonic crystal terahertz laser.
AB  - We present the design and the realization of active photonic crystal (PhC)
      semiconductor lasers. The PhC consists of semiconductor nanostructure pillars
      which provide gain at a quantized transition energy. The vertical layer sequence
      is that of a terahertz quantum cascade laser. Thereby, the artificial crystal
      itself provides the optical gain and the lateral confinement. The cavities do not
      rely on a central defect, the lasing is observed in flat-band regions at high
      symmetry points. The experimental results are in excellent agreement with the
      finite-difference time-domain simulations. For the vertical confinement a double
      metal waveguide is used. The lasers are showing a stable single-mode emission
      under all driving conditions. Varying the period of the PhC allows to tune the
      frequency by 400 GHz.

PMID- 19158910
TI  - Evidence of Raman-induced polarization pulling.
AB  - The interest towards passive control of the light polarization through nonlinear
      effects has been stimulated by recent works: in particular a polarization pulling
      effect has been obtained by means of stimulated Brillouin scattering. Here we
      investigate the condition for obtaining polarization pulling by exploiting the
      stimulated Raman scattering, which is most suitable for optical communications
      thanks to its large gain bandwidth. The role of the polarization-dependent Raman
      amplification and of the random fiber birefringence is clarified by theoretical
      considerations and numerical simulations starting from the vector theory of the
      Raman effect in optical fiber. Experiments carried out with a 1571-nm signal and
      high-power 1486-nm pump evidence the Raman-induced polarization pulling.

PMID- 19158911
TI  - Efficient emission-tunable VUV phosphors Na(2)GdF(2)PO(4):Tb(3+).
AB  - In this paper, we present the VUV-vis spectroscopic properties of
      Na(2)GdF(2)PO(4):Tb(3+) phosphors prepared at 700 degrees C. The phosphors
      exhibit some favorable luminescence characteristics such as intensive and broad
      absorption near 147/172 nm, high bright emission in whole doping concentration,
      and tunable chromaticity coordinates from blue to whitish and further to
      yellowish-green range by changing the doping concentration of Tb(3+). As a
      result, this series of phosphors Na(2)Gd(1-x)Tb(x)F(2)PO(4) can be considered as
      promising candidates for plasma display panels (PDPs) and Hg-free fluorescent
      tubes application.

PMID- 19158912
TI  - Sub-diffraction limited imaging with fluorophores exhibiting emission depletion
      upon saturation.
AB  - We present a simplified single-beam scheme for depletionbased sub-diffraction
      limited imaging which allows for less restrictive illumination conditions. This
      is done by introducing the concept of flu-orophores exhibiting emission depletion
      upon saturation. We discuss the circumstances under which such a depletion based
      process is possible, and derive the scaling of the spatial resolution utilizing
      this scheme. Next, we analyze the proper illumination conditions both in space
      and time required for sub diffraction limited imaging, and show that it is
      applicable only under pulsed excitation. Finally, our scheme's advantages and
      shortcomings relative to alternative realizations of depletion-based sub
      diffraction-limited microscopy are discussed.

PMID- 19158913
TI  - Three-wave shearing interferometer based on spatial light modulator.
AB  - The use of a SLM for the three-wave lateral shearing interference is proposed,
      and an eight-step phase-shifting scheme is developed for extracting phase
      information from three-wave interferograms. The two-dimensional phase of object
      is reconstructed from two phase differences which are calculated from two
      orthogonal sheared interferograms. The flexibility of SLM can be fully utilized
      in the sense of dynamical controlling of the direction and amount of shear, as
      well as phase shift. The numerical simulation and optical experiment are carried
      out to demonstrate the feasibility and reliability of the proposed scheme.

PMID- 19158914
TI  - Spectrally efficient next-generation optical access network incorporating a novel
      CWDM uplink combiner.
AB  - A novel wavelength division multiplexed subcarrier multiplexed (WDM/SCM)
      broadband (1-Gb/s per user) optical access network (OAN) architecture
      incorporating a coarse WDM (CWDM) uplink combiner is proposed. The concept is
      demonstrated through theoretical and experimental validation of a 10 x1-Gb/s
      quadurature-phase-shift keying (QPSK) SCM optical network. Low penalty
      transmission is demonstrated for a proof-of-principle dual channel system with a
      range of 25 km. In agreement with simulation, experiments show that channel
      spacings of only 1 GHz are viable for Q factors of more than 18 dB. Simulations
      indicate that the system will operate with 40 wavelengths, each carrying 10 SCM
      channels at 1 Gb/s.

PMID- 19158915
TI  - Spectral characterization of the voltage-sensitive dye di-4-ANEPPDHQ applied to
      probing live primary and immortalized neurons.
AB  - Spectral properties of a recently developed voltage-sensitive dye, di-4-ANEPPDHQ,
      were characterized as the dye was dissolved in the solvent dimethyl sulfoxide as
      the stock solution, in Hank's buffered salt solution as the staining solution,
      and bound to the plasma membrane of primary rat hippocampal neurons and
      immortalized mouse hypothalamic neurons (GT1-7) in vitro. Their dependence on the
      local chemical and electrical environment of dye molecules was determined. The
      excitation and emission peaks are 479 nm and 570 nm for the stained primary
      neurons, and 476 nm and 585 nm for the stained immortalized neurons. The
      excitation and emission bands of the stained GT1-7 neurons, defined as 50% peak
      intensity, are 429-516 nm and 544-648 nm, respectively.

PMID- 19158917
TI  - Electro-optic vortex-producing lenses using spiral-shaped ferroelectric domains.
AB  - We present electrically controlled wavefront modulators that simultaneously focus
      and introduce vorticity to an incident beam. These modulators are made out of
      spiral-shaped 180 degrees ferroelectric domains in lithium niobate; they have a
      virtually instantaneous response time, withstand high power and can be used
      throughout the transparency region of the material (0.4 - 5 microm).

PMID- 19158916
TI  - Flexible compact microdisk lasers on a polydimethylsiloxane (PDMS) substrate.
AB  - Compact microdisk cavities were fabricated on a polydimethylsiloxane substrate.
      The lasing of the flexible compact cavity was achieved with a low threshold
      power. The whispering-gallery mode of the microdisk was also characterized with
      three-dimensional finite-difference time-domain simulation. The curvature
      dependence in output power and threshold was also demonstrated by bending the
      microdisk cavity.

PMID- 19158918
TI  - Interferometric 3D tracking of several particles in a scanning laser focus.
AB  - High-Speed tracking of several particles allows measuring dynamic long-range
      interactions relevant to biotechnology and colloidal physics. In this paper we
      extend the successful technique of 3D back-focal plane interferometry to
      oscillating laser beams and show that two or more particles can be trapped and
      tracked with a precision of a few nanometers in all three dimensions. The
      tracking rate of several kHz is only limited by the scan speed of the beam
      steering device. Several tests proof the linearity and orthogonality of our
      detection scheme, which is of interest to optical tweezing applications and
      various metrologies. As an example we show the position cross-correlations of
      three diffusing particles in a scanning line optical trap.

PMID- 19158919
TI  - A plasmonic random composite with atypical refractive index.
AB  - We present a material composite consisting of randomly oriented elements governed
      by non-resonant interactions. By exploiting near-field plasmonic interaction in a
      dense ensemble of subwavelength-sized dielectric and metallic particles, we
      reveal that the group refractive index of the composite can be increased to be
      larger than the effective refractive indices of constituent metallic and
      dielectric parent composites. These findings introduce a new class of engineered
      photonic materials having customizable and atypical optical constants.

PMID- 19158920
TI  - Design and performance evaluation of dynamic wavelength scheduled hybrid WDM/TDM
      PON for distributed computing applications.
AB  - This paper investigates the design and implementation of distributed computing
      applications in local area network. We propose a novel Dynamical Wavelength
      Scheduled Hybrid WDM/TDM Passive Optical Network, which is termed as DWS-HPON.
      The system is implemented by using spectrum slicing techniques of broadband light
      source and overlay broadcast-signaling scheme. The Time-Wavelength Co-Allocation
      (TWCA) Problem is defined and an effective greedy approach to this problem is
      presented for aggregating large files in distributed computing applications. The
      simulations demonstrate that the performance is improved significantly compared
      with the conventional TDM-over-WDM PON.

PMID- 19158921
TI  - Integrated optical source of polarization entangled photons at 1310 nm.
AB  - We report the realization of a new polarization entangled photon-pair source
      based on a titanium-indiffused waveguide integrated on periodically poled lithium
      niobate pumped by a CW laser at 655 nm. The paired photons are emitted at the
      telecom wavelength of 1310 nm within a bandwidth of 0.7 nm. The quantum
      properties of the pairs are measured using a two-photon coalescence experiment
      showing a visibility of 85%. The evaluated source brightness, on the order of
      10(5) pairs s(-1)GHz(-1)mW(-1), associated with its compactness and reliability,
      demonstrates the source's high potential for long-distance quantum communication.

PMID- 19158922
TI  - Not-lithographic fabrication of micro-structured fiber Bragg gratings evanescent
      wave sensors.
AB  - This work is devoted to present and to demonstrate a novel approach for the
      fabrication of micro-structured fiber Bragg gratings (MSFBGs) to be employed as
      technological platform for advanced optochemical sensors. Basically, the MSFBG
      consists in a localized SRI sensitization of the grating by deep cladding
      stripping. The introduction of a perturbation or defect along the grating leads
      to the formation of a defect state inside the FBG spectral response that is
      tunable through the surrounding medium refractive index. While its spectral
      features for sensing and communication applications have been widely described
      and commented elsewhere, here a simple fabrication procedure is presented as
      suitable technological assessment enabling cost effective and simple MSFBG
      production. It relies on a two steps technique based on arc-discharge procedure
      as fiber pre-treatment and mask-less wet chemical etching to locally sensitize
      the FBG to external refractive index. The new, simple and low-cost approach
      overcomes some technological drawbacks related to previous fabrication techniques
      adopting patterned masking procedures during the etching process. This work
      demonstrates the effectiveness of the proposed method reporting a detailed
      description of single and two defects MSFBG fabrication.

PMID- 19158923
TI  - Sagnac secret sharing over telecom fiber networks.
AB  - We report the first Sagnac quantum secret sharing (in three-and four-party
      implementations) over 1550 nm single mode fiber (SMF) networks, using a single
      qubit protocol with phase encoding. Our secret sharing experiment has been based
      on a single qubit protocol, which has opened the door to practical secret sharing
      implementation over fiber telecom channels and in free-space. The previous
      quantum secret sharing proposals were based on multiparticle entangled states,
      difficult in the practical implementation and not scalable. Our experimental data
      in the three-party implementation show stable (in regards to birefringence drift)
      quantum secret sharing transmissions at the total Sagnac transmission loop
      distances of 55-75 km with the quantum bit error rates (QBER) of 2.3-2.4% for the
      mean photon number micro?= 0.1 and 1.7-2.1% for micro= 0.3. In the four-party
      case we have achieved quantum secret sharing transmissions at the total Sagnac
      transmission loop distances of 45-55 km with the quantum bit error rates (QBER)
      of 3.0-3.7% for the mean photon number micro= 0.1 and 1.8-3.0% for micro?= 0.3.
      The stability of quantum transmission has been achieved thanks to our new concept
      for compensation of SMF birefringence effects in Sagnac, based on a polarization
      control system and a polarization insensitive phase modulator. The measurement
      results have showed feasibility of quantum secret sharing over telecom fiber
      networks in Sagnac configuration, using standard fiber telecom components.

PMID- 19158924
TI  - Synthesis of fibrous nanoparticle aggregates by femtosecond laser ablation in
      air.
AB  - In this article we report the synthesis of nanoparticles using femtosecond laser
      ablation with MHz pulse frequency at room temperature in air. Nanoparticles
      agglomerate by fusion, and form interweaving fibrous structures that show certain
      degree of self-assembly. It is found that there is a threshold-like pulse
      frequency at which fibrous nanoparticle aggregates start to form. The growth
      mechanism can be explained by existing theories regarding nanoparticle formation
      through femtosecond laser ablation. The threshold pulse frequency is in good
      agreement with the time to start nanoparticle formation, which has been derived
      numerically by previous analyses.

PMID- 19158925
TI  - 8-fs pulses from a compact Er:fiber system: quantitative modeling and
      experimental implementation.
AB  - We demonstrate an all-fiber turnkey source of extremely stable 2-cycle pulses at
      a center wavelength of 1.17 microm. Taylor-cut highly nonlinear germano-silica
      bulk fibers (HNFs) provide smooth supercontinua with a bandwidth of 560 nm and a
      spectral shape precisely controlled by the dispersion of the fiber and the phase
      of the 1.55 microm pump pulses. Alternatively these fibers are capable of
      generating pulses with central wavelengths continuously tunable from 0.9 microm
      up to 1.4 microm. These results are based on parameter-free simulations of
      nonlinear pulse propagation including higher-order dispersion as well as
      instantaneous Kerr and retarded Raman contributions.

PMID- 19158926
TI  - Analysis of propagation characteristics in the surface plasmon polariton gap
      waveguides by method of lines.
AB  - A numerical study of the complex propagation constants of a surface plasmon
      polariton gap waveguide (SPGW) that was nanometric in size is performed by the
      method of lines (MoL). The validity of the code based on the MoL is examined by
      comparing the present results with those calculated using a volume integral
      equation, which is a completely different numerical technique from the MoL. The
      dependences of the complex propagation constants on the sizes of the SPGWs are
      investigated in detail and the fundamental propagation characteristics of SPGWs
      are revealed. Three kinds of SPGW structures (slab-slab, slab-plate and staggered
      slab-slab) are examined with a view to reducing the attenuation constants and the
      spot size to nanometric size. It is found that the nanometric field confinement
      can be controlled by using the staggered slab-slab structure of SPGW without a
      large change in the propagation constants.

PMID- 19158927
TI  - Photon entanglement signatures in difference-frequency-generation.
AB  - In response to quantum optical fields, pairs of molecules generate coherent
      nonlinear spectroscopy signals. Homodyne signals are given by sums over terms
      each being a product of Liouville space pathways of the pair of molecules times
      the corresponding optical field correlation function. For classical fields all
      field correlation functions may be factorized and become identical products of
      field amplitudes. The signal is then given by the absolute square of a
      susceptibility which in turn is a sum over pathways of a single molecule. The
      molecular pathways of different molecules in the pair are uncorrelated in this
      case (each path of a given molecule can be accompanied by any path of the other).
      However, entangled photons create an entanglement between the molecular
      pathways.We use the superoperator nonequlibrium Green's functions formalism to
      demonstrate the signatures of this pathway-entanglement in the difference
      frequency generation signal. Comparison is made with an analogous incoherent two
      photon fluorescence signal.

PMID- 19158928
TI  - Asymmetric split ring resonators for optical sensing of organic materials.
AB  - Asymmetric Split Ring Resonators are known to exhibit resonant modes where the
      optical electric field is strongest near the ends of the arms, thereby increasing
      the sensitivity of spectral techniques such as surface enhanced Raman scattering
      (SERS). By producing asymmetry in the structures, the two arms of the ring
      produce distinct plasmonic resonances related to their lengths - but are also
      affected by the presence of the other arm. This combination leads to a steepening
      of the slope of the reflection spectrum between the resonances that increases the
      sensitivity of the resonant behavior to the addition of different molecular
      species. We describe experimental results, supported by simulation, on the
      resonances of a series of circular split ring resonators with different gap and
      section lengths--at wavelengths in the mid-infra red regions of the spectrum--and
      their utilization for highly sensitive detection of organic compounds. We have
      used thin films of PMMA with different thicknesses, resulting in characteristic
      shifts from the original resonance. We also demonstrate matching of asymmetric
      split ring resonators to a molecular resonance of PMMA.

PMID- 19158929
TI  - On chip tunable micro ring resonator actuated by electrowetting.
AB  - We demonstrate a tunable on chip polymer waveguide micro ring resonator (MRR)
      device. The transmission spectrum and extinction ratio are controlled by
      electrowetting on dielectric (EWOD), via the application of voltage to a droplet.
      As a result the droplet covers a portion of the MRR waveguide and changes its
      effective refractive index. This method can be used for efficiently tuning a
      variety of on chip optical devices, as it offers high index contrast, electrical
      control and low power consumption.

PMID- 19158930
TI  - Nonlinear optical properties of 2,4,5-Trimethoxy-4-nitrochalcone: observation of
      two-photon-induced excited-state nonlinearities.
AB  - We report experimental investigations of optical nonlinearities and nonlinear
      dynamics in acetone solution of 2,4,5-Trimethoxy-4- nitrochalcone. By performing
      Z-scans with femtosecond laser pulses at low excitation intensity, two-photon
      absorption (2PA) and third-order nonlinear refraction are measured. As laser
      excitation intensity exceeds a critical value, however, the interplay between
      third- and fifth-order nonlinearities is observed. It is also confirmed that
      fifth-order processes mainly originate from 2PA-induced excited-state
      nonlinearities by conducting femtosecond time-resolved degenerate pump-probe
      measurements. All the nonlinear parameters are determined unambiguously in the
      near infrared region of the 2PA cross-section, second-order hyperpolarizability,
      excited-state absorption cross-section, excited-state refraction cross-section,
      lifetime of excited states induced by 2PA, and critical population of the excited
      states in 2,4,5-Trimethoxy-4-nitrochalcone molecule.

PMID- 19158931
TI  - Analysis of surface plasmon waves in metaldielectric- metal structures and the
      criterion for negative refractive index.
AB  - Surface plasmon waves in metal-dielectric-metal structures have been
      theoretically examined. Because of the existence of evanescent waves that can
      have comparable or smaller decay rates than the propagating waves, the sign of
      dispersion does not necessarily indicate the sign of effective refractive index
      for these structures. By using the direction of energy decay to distinguish the
      sign of index, we have obtained different results and insights from previous
      reports. We also propose an approach to increase the bandwidth and decrease the
      loss of negative index surface Plasmon propagation in the MDM structure, by
      simply changing the properties of its dielectric layer.

PMID- 19158932
TI  - Dependencies of micro-pillar cavity quality factors calculated with finite
      element methods.
AB  - We present simulation results for optical modes in micro-pillar cavities that
      were computed with the finite element method and that show good agreement with
      experimental data. By means of this viable tool various influences on the quality
      factor of the fundamental mode were calculated: Firstly, the light confinement
      depends strongly on the absorption of the semiconductor cavity material. Here we
      were able to determine absolute maximum quality factors achievable in a GaAs/AlAs
      Bragg micro-pillar cavity. Furthermore, small pillar diameters as well as the
      inclination of pillar sidewalls show critical features with respect to light
      confinement. Additional effects of the top and bottom Bragg stacks in the pillar
      were calculated as well.

PMID- 19158933
TI  - MicroRNAs 373 and 520c are downregulated in prostate cancer, suppress CD44
      translation and enhance invasion of prostate cancer cells in vitro.
AB  - Prostate cancer (PCa), like most human cancers, features dysregulated CD44
      expression. It loses expression of CD44 standard (CD44s), present in benign
      epithelium, and overexpresses a less abundant splice isoform, CD44v7-10.
      MicroRNAs 373 and 520c putatively regulate CD44. The levels of these two
      microRNAs were measured in matched benign and malignant patient tissues and in
      prostate cell lines. The effects of their transfection on CD44 mRNA and protein
      were documented. Whether these miRNAs act on CD44 promoter, or its 3'
      untranslated region (UTR), was studied with luciferase reporter constructs and
      their influences on migration and invasion were determined in PC-3M cells. miR
      373 and miR-520c expression were decreased in PCa cell lines and tissues, in
      proportion to their decreases in total CD44 mRNA. Exogenous miR-373 caused a dose
      dependent increase in total CD44 RNA, but a decrease in CD44v7-10 RNA, with an
      optimal dose at 6 nM. At the protein level, however, both microRNAs suppressed
      CD44. Both migration and invasion were stimulated by miR-373 and miR-520c. The
      microRNAs had no effect on the CD44 promoter, but did exhibit 3'UTR binding. In
      conclusion, miR-373 and miR-520c exert their effect in PCa by preventing the
      translation of CD44 RNA, rather than by degrading the RNA. Despite this
      observation, they exert pro-invasive functional effects, as previously described
      in breast cancer cells. Their effects are mediated by binding CD44 3'UTR.

PMID- 19158934
TI  - Comparative analysis of paired- and homeodomain-specific roles in PAX3-FKHR
      oncogenesis.
AB  - The alveolar rhabdomyosarcoma-associated t(2;13) chromosomal translocation
      produces an oncogenic fusion transcription factor PAX3-FKHR that combines the N
      terminal DNA binding domains (paired domain and homeodomain) of PAX3 with the C
      terminal activation domain of FKHR. In the context of PAX3-FKHR, the two DNA
      binding domains can work either cooperatively or autonomously in regulating gene
      transcription. The latter is a gain-of-function unique to the fusion protein. The
      biological activities driven by the individual DNA binding domain remains poorly
      defined. In this study, we express PAX3-FKHR mutants that contain only a single
      functional DNA binding domain into C2C12 myoblasts, and measured the in vitro and
      in vivo behaviors of these cells. We show that only the homeodomain-specific PAX3
      FKHR mutant recapitulates the in vitro transformation properties of the wild type
      fusion protein. However, despite the differential responses in vitro, both the
      paired domain- and the homeodomain-specific PAX3-FKHR mutants promote tumor
      development from myoblasts in vivo. Our results suggest an important role for the
      gain of the paired domain- and the homeodomain-transcription activities in the
      PAX3-FKHR malignant transformation process.

PMID- 19158935
TI  - Mammaglobin, a valuable diagnostic marker for metastatic breast carcinoma.
AB  - Identification of metastasis and occult micrometastases of breast cancer demands
      sensitive and specific diagnostic markers. In this study, we assessed the utility
      of a mouse monoclonal antibody to human mammaglobin for one such purpose.
      Immunohistochemical stains were performed on paraffin-embedded sections from a
      total of 284 cases, which consisted of primary breast invasive carcinomas (41
      cases) with matched metastases to ipsilateral axillary lymph nodes, metastatic
      breast carcinoma to liver (1 case) and kidney (1 case), non-breast neoplasms (161
      cases), and normal human tissues (39 cases). The results showed 31 of the 41
      cases of primary breast cancer with axillary lymph node metastases were positive
      for mammaglobin (76%). In the meantime, we documented expression of mammaglobin
      in occasional cases of endometrial carcinoma (17%). Our data further validated
      that mammaglobin is a valuable diagnostic marker for metastatic carcinoma of
      breast origin, although endometrial carcinoma should be considered as a major
      differential diagnosis.

PMID- 19158936
TI  - Distinct regulation of cell cycle and survival in lymphocytes from patients with
      Alzheimer's disease and amyotrophic lateral sclerosis.
AB  - Alterations in cell cycle progression seem to be associated with neuronal death
      in Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). We
      previously reported disturbances in the control of cell survival/death fate in
      immortalized lymphocytes from AD patients. These cell cycle dysfunction and
      impaired apoptosis were considered systemic manifestations of AD disease. The
      purpose of this study was to evaluate whether these abnormalities are
      characteristic of AD, or they may be seen in other neurodegenerative disorders
      such ALS. Our results indicate that alterations in signaling molecules, Akt and
      ERK1/2, and in the cyclin-dependent kinase complex inhibitors (CDKis) p21(Cip1)
      and p27(Kip1) are detectable in lymphoblasts from AD patients, but not in ALS
      patients, suggesting that these variables may be considered for the development
      of biomarkers of AD. However, lymphocytes from ALS patients do not represent a
      useful model to study cell cycle-related events associated with neurodegeneration
      of motoneurons.

PMID- 19158938
TI  - North american erionite-associated mesothelioma with pleural plaques and
      pulmonary fibrosis: a case report.
AB  - Erionite, a fibrous zeolite mineral, has been categorized as a class I
      carcinogenic agent for its causative role in mesothelioma. In select villages in
      Turkey, erionite is the cause of more than 50% of mesotheliomas. In contrast, in
      the United States mesotheliomas are frequently associated with asbestos exposure.
      We describe the first reported case of a patient with erionite-associated pleural
      mesothelioma with classic pathologic changes typical of asbestos-related
      pulmonary and pleural pathology. This case report indicates that in addition to
      Turkey, erionite-associated disease can occur in North America and that subjects
      with erionite exposure are not only at risk of developing mesothelioma, but may
      develop interstitial fibrosis and additional pulmonary pathology impacting lung
      function and patient survival.

PMID- 19158937
TI  - Cortical Alzheimer type pathology does not influence tau pathology in progressive
      supranuclear palsy.
AB  - Alzheimer disease (AD) is characterized by numerous senile plaques (SP) in
      addition to widespread neocortical neurofibrillary tangles (NFT). Some elderly
      have pathologic aging (PA), which is characterized by numerous SP composed of
      diffuse amyloid deposits with few or no NFT confined to the limbic lobe. Both AD
      and PA represent a range of Alzheimer type pathology (ATP). Some cases of
      progressive supranuclear palsy (PSP) have concurrent ATP, but the relationship
      between ATP and PSP has not been addressed. In this study, a consecutive series
      of PSP cases were divided into three groups according to the degree of concurrent
      ATP - pure PSP, PSP/PA and PSP/AD. Braak NFT stage was significantly greater in
      PSP/AD compared with both PSP/PA and PSP. Among the pathologic variables studied
      in middle frontal, superior temporal and motor cortices, there were no
      differences between PSP and PSP/PA except for SP. In PSP/AD, there was greater
      neuronal tau pathology (pretangles, NFT and neuropil threads) in middle frontal
      and superior temporal cortices, probably a reflection of ATP since there was no
      comparable increase in PSP-related glial tau pathology in these regions. The
      APOEvarepsilon4 allele frequency was significantly higher in PSP/PA and PSP/AD
      than in PSP. These results strongly argue that ATP in PSP represents independent
      disease processes even when present in the same brain.

PMID- 19158939
TI  - Physical activity, muscle function, falls and fractures.
AB  - STUDY DESIGN: A thematic review. OBJECTIVES: To evaluate if physical activity
      enhances muscle strength, improves balance, and reduces the fall frequency and
      the fracture incidence. BACKGROUND: One of the major medical problems of today is
      the increasing incidence of fragility fractures. Muscle strength and fall is one
      of the major determinants of a fracture. If physical activity could increase
      muscle strength, improve balance and reduce the fall frequency, then training
      could be recommended as prevention for fractures. METHODS: The review used
      Medline (Pub Med) and the search words exercise, physical activity, muscle
      strength, balance, falls, fractures. Randomized controlled trials (RCT) were
      predominantly included, although this not is a systematic review. RESULTS: The
      evidence that physical activity modifies the risk factors for fall is compelling,
      although RCT with fractures as end point are lacking. Physical activity is
      associated with improved muscle strength, co-ordination and balance. Physical
      training increases muscle strength also in octogenarians by up to 200%, i.e. a
      much more pronounced effect than the corresponding increase in muscle volume or
      bone mass. There is also evidence that physical activity decreases the actual
      number of falls. Observational cohort and case-control studies imply that
      physical activity is associated with reduced hip fracture risk. If exercise
      reduces the number of vertebral fractures and other fragility fractures are less
      evaluated. CONCLUSIONS: Physical activity in older ages can be recommended to
      improve muscle strength and balance, to reduce the risk to fall and fractures,
      although the highest level of evidence - RCT with fracture as endpoint - is
      lacking.

PMID- 19158940
TI  - Nutritional status of cancer patients in chemotherapy; dietary intake, nitrogen
      balance and screening.
AB  - OBJECTIVE: To evaluate a short screening sheet (SSM) for malnutrition and to
      investigate the nutritional status of patients receiving chemotherapy for cancer
      of the lungs, colon or breast at an outpatient clinic. DESIGN: Full nutritional
      assessment was conducted to define malnutrition and validate the SSM.
      Additionally, weight change from earlier healthy weight was evaluated, and
      calculations for intake of energy-giving nutrients (three-day-weighed food
      records) and protein balance were performed. After the evaluation study, the SSM
      was tested in clinical routine and data collected about patients' need for
      nutritional counseling. SUBJECTS: Patients at the outpatient clinic of the
      Department of Oncology at Landspitali-University Hospital (n=30 with lung-, colon
      or breast cancer in the study population, n=93 with all cancer type in clinical
      routine screening). RESULTS: Malnutrition was defined by full nutritional
      assessment in 20% of the participating patients and SSM had high sensitivity and
      specificity. Declining nutritional status of the patients was seen as a negative
      nitrogen balance and unintentional weight loss from healthy weight, but not as
      total energy intake, recent weight loss or underweight. The test of SSM in
      clinical routine showed that 40% were malnourished. According to the patients,
      80% needed nutritional counseling but only 17% had such counseling. CONCLUSION:
      Screening (SSM) for malnutrition in cancer patients is a valid simple approach to
      define cancer patients for nutritional care. More patients regard themselves in
      need for nutritional counseling than the number of patients really achieving any.

PMID- 19158941
TI  - No acute effects of grape juice on appetite, implicit memory and mood.
AB  - BACKGROUND: Animal experiments document effects of grape juice on cognitive
      performance and motor skills, and observational studies in humans suggest an
      inverse association between flavonoid intake and cognitive decline. These effects
      may be related to the antioxidant properties of polyphenols. Juice consumption
      and flavonoid intake may also affect appetite. OBJECTIVE: To study the acute
      effects of grape juice consumption on appetite, mood and implicit memory during a
      time of increased lethargy - the post-lunch dip. DESIGN: Thirty-five participants
      with a mean age of 26 years who smoked a mean of 11 cigarettes/day for 8 years
      were included in the study. It included a practice session and two treatment
      sessions. All sessions involved consumption of grape juice or an energy-matched
      placebo with lunch followed by assessments of mood, implicit memory, appetite and
      food intake. RESULTS: Mood decreased over time for both treatments, but there
      were no differences after lunch between grape juice and placebo for any measure.
      CONCLUSION: This study did not document any acute effects of grape juice
      consumption on mood, implicit memory, appetite or food intake in smokers.

PMID- 19158942
TI  - Hierarchical Multiresolution Approaches for Dense Point-Level Breast Cancer
      Treatment Data.
AB  - The analysis of point-level (geostatistical) data has historically been plagued
      by computational difficulties, owing to the high dimension of the nondiagonal
      spatial covariance matrices that need to be inverted. This problem is greatly
      compounded in hierarchical Bayesian settings, since these inversions need to take
      place at every iteration of the associated Markov chain Monte Carlo (MCMC)
      algorithm. This paper offers an approach for modeling the spatial correlation at
      two separate scales. This reduces the computational problem to a collection of
      lower-dimensional inversions that remain feasible within the MCMC framework. The
      approach yields full posterior inference for the model parameters of interest, as
      well as the fitted spatial response surface itself. We illustrate the importance
      and applicability of our methods using a collection of dense point-referenced
      breast cancer data collected over the mostly rural northern part of the state of
      Minnesota. Substantively, we wish to discover whether women who live more than a
      60-mile drive from the nearest radiation treatment facility tend to opt for
      mastectomy over breast conserving surgery (BCS, or "lumpectomy"), which is less
      disfiguring but requires 6 weeks of follow-up radiation therapy. Our hierarchical
      multiresolution approach resolves this question while still properly accounting
      for all sources of spatial association in the data.

PMID- 19158943
TI  - Improved AIC Selection Strategy for Survival Analysis.
AB  - In survival analysis, it is of interest to appropriately select significant
      predictors. In this paper, we extend the AIC(C) selection procedure of Hurvich
      and Tsai to survival models to improve the traditional AIC for small sample
      sizes. A theoretical verification under a special case of the exponential
      distribution is provided. Simulation studies illustrate that the proposed method
      substantially outperforms its counterpart: AIC, in small samples, and competes it
      in moderate and large samples. Two real data sets are also analyzed.

PMID- 19158944
TI  - Molecular cloning and characterization of pigeon (Columba liva) ubiquitin and
      ubiquitin-conjugating enzyme genes from pituitary gland library.
AB  - In the study of the regulation of incubation, broodiness and laying performance
      in pigeons (Columba liva), a cDNA library, which was enriched with full-length
      brooding-related genes, was constructed by SMART LD-PCR techniques using the
      pituitary glands of incubating White King pigeons. The titers of optimal primary
      libraries were 1.54x10(6) pfu/mL and 1.80x10(6) pfu/mL and the titers of
      amplified libraries were 1.89x10(8) pfu/mL and 2.32x10(9 )pfu/mL. The percentages
      of recombinant clones of primary libraries and amplified libraries were all over
      90%. A positive clone was sequenced and named ubiquitin based on the highly
      similar from other species. The fragment has the four initial codons of ATG, a
      termination codon of TAA and a signal sequence of AATAAA for adding the poly-A
      tail. The open reading frame of 918bp encodes 305 amino acids (NCBI accession
      number is EU981283). Recombinant pigeon ubiquitin protein was efficiently
      expressed with the form of insoluble inclusion bodies in E. coli BL21 transformed
      with a pET28a(+) expression vector containing the DNA sequence encoding mature
      pigeon ubiquitin. The molecular weight of expressed protein is the same as
      predicted size of approximately 35kD. To improve the efficiency of cloning full
      length cDNA, strategies of RACE combined with cDNA library were used. The length
      of pigeons ubiquitin-conjugating enzyme gene obtained was 1263 bp containing a
      complete open reading frame of 435 bp that encodes 144 aa (NCBI accession number
      is EU914824). The results of this study not only provide a starting point for
      further study of ubiquitin function in pigeon species, but also provide a
      starting point for investigating the brooding mechanisms of pigeons.

PMID- 19158945
TI  - Impaired nuclear Nrf2 translocation undermines the oxidative stress response in
      Friedreich ataxia.
AB  - BACKGROUND: Friedreich ataxia originates from a decrease in mitochondrial
      frataxin, which causes the death of a subset of neurons. The biochemical
      hallmarks of the disease include low activity of the iron sulfur cluster
      containing proteins (ISP) and impairment of antioxidant defense mechanisms that
      may play a major role in disease progression. METHODOLOGY/PRINCIPAL FINDINGS: We
      thus investigated signaling pathways involved in antioxidant defense mechanisms.
      We showed that cultured fibroblasts from patients with Friedreich ataxia
      exhibited hypersensitivity to oxidative insults because of an impairment in the
      Nrf2 signaling pathway, which led to faulty induction of antioxidant enzymes.
      This impairment originated from previously reported actin remodeling by hydrogen
      peroxide. CONCLUSIONS/SIGNIFICANCE: Thus, the defective machinery for ISP
      synthesis by causing mitochondrial iron dysmetabolism increases hydrogen peroxide
      production that accounts for the increased susceptibility to oxidative stress.

PMID- 19158946
TI  - IGFBP3 colocalizes with and regulates hypocretin (orexin).
AB  - BACKGROUND: The sleep disorder narcolepsy is caused by a vast reduction in
      neurons producing the hypocretin (orexin) neuropeptides. Based on the tight
      association with HLA, narcolepsy is believed to result from an autoimmune attack,
      but the cause of hypocretin cell loss is still unknown. We performed gene
      expression profiling in the hypothalamus to identify novel genes dysregulated in
      narcolepsy, as these may be the target of autoimmune attack or modulate
      hypocretin gene expression. METHODOLOGY/PRINCIPAL FINDINGS: We used microarrays
      to compare the transcriptome in the posterior hypothalamus of (1) narcoleptic
      versus control postmortem human brains and (2) transgenic mice lacking hypocretin
      neurons versus wild type mice. Hypocretin was the most downregulated gene in
      human narcolepsy brains. Among many additional candidates, only one, insulin-like
      growth factor binding protein 3 (IGFBP3), was downregulated in both human and
      mouse models and co-expressed in hypocretin neurons. Functional analysis
      indicated decreased hypocretin messenger RNA and peptide content, and increased
      sleep in transgenic mice overexpressing human IGFBP3, an effect possibly mediated
      through decreased hypocretin promotor activity in the presence of excessive
      IGFBP3. Although we found no IGFBP3 autoantibodies nor a genetic association with
      IGFBP3 polymorphisms in human narcolepsy, we found that an IGFBP3 polymorphism
      known to increase serum IGFBP3 levels was associated with lower CSF hypocretin-1
      in normal individuals. CONCLUSIONS/SIGNIFICANCE: Comparison of the transcriptome
      in narcolepsy and narcolepsy model mouse brains revealed a novel dysregulated
      gene which colocalized in hypocretin cells. Functional analysis indicated that
      the identified IGFBP3 is a new regulator of hypocretin cell physiology that may
      be involved not only in the pathophysiology of narcolepsy, but also in the
      regulation of sleep in normal individuals, most notably during adolescence.
      Further studies are required to address the hypothesis that excessive IGFBP3
      expression may initiate hypocretin cell death and cause narcolepsy.

PMID- 19158947
TI  - Evolution of reproductive morphology in leaf endophytes.
AB  - The endophytic lifestyle has played an important role in the evolution of the
      morphology of reproductive structures (body) in one of the most problematic
      groups in fungal classification, the Leotiomycetes (Ascomycota). Mapping fungal
      morphologies to two groups in the Leiotiomycetes, the Rhytismatales and
      Hemiphacidiaceae reveals significant divergence in body size, shape and
      complexity. Mapping ecological roles to these taxa reveals that the groups
      include endophytic fungi living on leaves and saprobic fungi living on duff or
      dead wood. Finally, mapping of the morphologies to ecological roles reveals that
      leaf endophytes produce small, highly reduced fruiting bodies covered with fungal
      tissue or dead host tissue, while saprobic species produce large and intricate
      fruiting bodies. Intriguingly, resemblance between asexual conidiomata and sexual
      ascomata in some leotiomycetes implicates some common developmental pathways for
      sexual and asexual development in these fungi.

PMID- 19158949
TI  - Metabolomic profiling of drug responses in acute myeloid leukaemia cell lines.
AB  - Combined bezafibrate (BEZ) and medroxyprogesterone acetate (MPA) exert unexpected
      antileukaemic activities against acute myeloid leukaemia (AML) and these
      activities are associated with the generation of reactive oxygen species (ROS)
      within the tumor cells. Although the generation of ROS by these drugs is
      supported by preceding studies including our own, the interrelationship between
      the cellular effects of the drugs and ROS generation is not well understood. Here
      we report the use of NMR metabolomic profiling to further study the effect of BEZ
      and MPA on three AML cell lines and to shed light on the underlying mechanism of
      action. For this we focused on drug effects induced during the initial 24 hours
      of treatment prior to the onset of overt cellular responses and examined these in
      the context of basal differences in metabolic profiles between the cell lines.
      Despite their ultimately profound cellular effects, the early changes in
      metabolic profiles engendered by these drugs were less pronounced than the
      constitutive metabolic differences between cell types. Nonetheless, drug
      treatments engendered common metabolic changes, most markedly in the response to
      the combination of BEZ and MPA. These responses included changes to TCA cycle
      intermediates consistent with recently identified chemical actions of ROS.
      Notable amongst these was the conversion of alpha-ketoglutarate to succinate
      which was recapitulated by the treatment of cell extracts with exogenous hydrogen
      peroxide. These findings indicate that the actions of combined BEZ and MPA
      against AML cells are indeed mediated downstream of the generation of ROS rather
      than some hitherto unsuspected mechanism. Moreover, our findings demonstrate that
      metabolite profiles represent highly sensitive markers for genomic differences
      between cells and their responses to external stimuli. This opens new
      perspectives to use metabolic profiling as a tool to study the rational
      redeployment of drugs in new disease settings.

PMID- 19158948
TI  - Recombinant mouse PAP has pH-dependent ectonucleotidase activity and acts through
      A(1)-adenosine receptors to mediate antinociception.
AB  - Prostatic acid phosphatase (PAP) is expressed in nociceptive neurons and
      functions as an ectonucleotidase. When injected intraspinally, the secretory
      isoforms of human and bovine PAP protein have potent and long-lasting
      antinociceptive effects that are dependent on A(1)-adenosine receptor (A(1)R)
      activation. In this study, we purified the secretory isoform of mouse (m)PAP
      using the baculovirus expression system to determine if recombinant mPAP also had
      antinociceptive properties. We found that mPAP dephosphorylated AMP, and to a
      much lesser extent, ADP at neutral pH (pH 7.0). In contrast, mPAP
      dephosphorylated all purine nucleotides (AMP, ADP, ATP) at an acidic pH (pH 5.6).
      The transmembrane isoform of mPAP had similar pH-dependent ectonucleotidase
      activity. A single intraspinal injection of mPAP protein had long-lasting (three
      day) antinociceptive properties, including antihyperalgesic and antiallodynic
      effects in the Complete Freund's Adjuvant (CFA) inflammatory pain model. These
      antinociceptive effects were transiently blocked by the A(1)R antagonist 8
      cyclopentyl-1, 3-dipropylxanthine (CPX), suggesting mPAP dephosphorylates
      nucleotides to adenosine to mediate antinociception just like human and bovine
      PAP. Our studies indicate that PAP has species-conserved antinociceptive effects
      and has pH-dependent ectonucleotidase activity. The ability to metabolize
      nucleotides in a pH-dependent manner could be relevant to conditions like
      inflammation where tissue acidosis and nucleotide release occur. Lastly, our
      studies demonstrate that recombinant PAP protein can be used to treat chronic
      pain in animal models.

PMID- 19158950
TI  - Mineral preservatives in the wood of Stradivari and Guarneri.
AB  - Following the futile efforts of generations to reach the high standard of
      excellence achieved by the luthiers in Cremona, Italy, by variations of design
      and plate tuning, current interest is being focused on differences in material
      properties. The long-standing question whether the wood of Stradivari and
      Guarneri were treated with wood preservative materials could be answered only by
      the examination of wood specimens from the precious antique instruments. In a
      recent communication (Nature, 2006), we reported about the degradation of the
      wood polymers in instruments of Stradivari and Guarneri, which could be explained
      only by chemical manipulations, possibly by preservatives. The aim of the current
      work was to identify the minerals from the small samples of the maple wood which
      were available to us from the antique instruments. The ashes of wood from one
      violin and one cello by Stradivari, two violins by Guarneri, one viola by H. Jay,
      one violin by Gand-Bernardel were analyzed and compared with a variety of
      commercial tone woods. The methods of analysis were the following: back-scattered
      electron imaging, X-ray fluorescence maps for individual elements, wave-length
      dispersive spectroscopy, energy dispersive X-ray spectroscopy and quantitative
      microprobe analysis. All four Cremonese instruments showed the unmistakable signs
      of chemical treatments in the form of chemicals which are not present in natural
      woods, such as BaSO4, CaF2, borate, and ZrSiO4. In addition to these, there were
      also changes in the common wood minerals. Statistical evaluation of 12 minerals
      by discriminant analysis revealed: a. a difference among all four Cremona
      instruments, b. the difference of the Cremonese instruments from the French and
      English antiques, and c. only the Cremonese instruments differed from all
      commercial woods. These findings may provide the answer why all attempts to
      recreate the Stradivarius from natural wood have failed. There are many obvious
      implications with regard to how the green tone wood should be treated, which
      chould lead to changes in the practice of violin-making. This research should
      inspire others to analyze more antique violins for their chemical contents.

PMID- 19158952
TI  - Compressive sensing DNA microarrays.
AB  - Compressive sensing microarrays (CSMs) are DNA-based sensors that operate using
      group testing and compressive sensing (CS) principles. In contrast to
      conventional DNA microarrays, in which each genetic sensor is designed to respond
      to a single target, in a CSM, each sensor responds to a set of targets. We study
      the problem of designing CSMs that simultaneously account for both the
      constraints from CS theory and the biochemistry of probe-target DNA
      hybridization. An appropriate cross-hybridization model is proposed for CSMs, and
      several methods are developed for probe design and CS signal recovery based on
      the new model. Lab experiments suggest that in order to achieve accurate
      hybridization profiling, consensus probe sequences are required to have sequence
      homology of at least 80% with all targets to be detected. Furthermore, out-of
      equilibrium datasets are usually as accurate as those obtained from equilibrium
      conditions. Consequently, one can use CSMs in applications in which only short
      hybridization times are allowed.

PMID- 19158951
TI  - Mitochondrial targeted coenzyme Q, superoxide, and fuel selectivity in
      endothelial cells.
AB  - BACKGROUND: Previously, we reported that the "antioxidant" compound "mitoQ"
      (mitochondrial-targeted ubiquinol/ubiquinone) actually increased superoxide
      production by bovine aortic endothelial (BAE) cell mitochondria incubated with
      complex I but not complex II substrates. METHODS AND RESULTS: To further define
      the site of action of the targeted coenzyme Q compound, we extended these studies
      to include different substrate and inhibitor conditions. In addition, we assessed
      the effects of mitoquinone on mitochondrial respiration, measured respiration and
      mitochondrial membrane potential in intact cells, and tested the intriguing
      hypothesis that mitoquinone might impart fuel selectivity in intact BAE cells. In
      mitochondria respiring on differing concentrations of complex I substrates,
      mitoquinone and rotenone had interactive effects on ROS consistent with redox
      cycling at multiple sites within complex I. Mitoquinone increased respiration in
      isolated mitochondria respiring on complex I but not complex II substrates.
      Mitoquinone also increased oxygen consumption by intact BAE cells. Moreover, when
      added to intact cells at 50 to 1000 nM, mitoquinone increased glucose oxidation
      and reduced fat oxidation, at doses that did not alter membrane potential or
      induce cell toxicity. Although high dose mitoquinone reduced mitochondrial
      membrane potential, the positively charged mitochondrial-targeted cation,
      decyltriphenylphosphonium (mitoquinone without the coenzyme Q moiety), decreased
      membrane potential more than mitoquinone, but did not alter fuel selectivity.
      Therefore, non-specific effects of the positive charge were not responsible and
      the quinone moiety is required for altered nutrient selectivity. CONCLUSIONS: In
      summary, the interactive effects of mitoquinone and rotenone are consistent with
      redox cycling at more than one site within complex I. In addition, mitoquinone
      has substrate dependent effects on mitochondrial respiration, increases
      repiration by intact cells, and alters fuel selectivity favoring glucose over
      fatty acid oxidation at the intact cell level.

PMID- 19158953
TI  - Scapinin, the protein phosphatase 1 binding protein, enhances cell spreading and
      motility by interacting with the actin cytoskeleton.
AB  - Scapinin, also named phactr3, is an actin and protein phosphatase 1 (PP1) binding
      protein, which is expressed in the adult brain and some tumor cells. At present,
      the role(s) of scapinin in the brain and tumors are poorly understood. We show
      that the RPEL-repeat domain of scapinin, which is responsible for its direct
      interaction with actin, inhibits actin polymerization in vitro. Next, we
      established a Hela cell line, where scapinin expression was induced by
      tetracycline. In these cells, expression of scapinin stimulated cell spreading
      and motility. Scapinin was colocalized with actin at the edge of spreading cells.
      To explore the roles of the RPEL-repeat and PP1-binding domains, we expressed
      wild-type and mutant scapinins as fusion proteins with green fluorescence protein
      (GFP) in Cos7 cells. Expression of GFP-scapinin (wild type) also stimulated cell
      spreading, but mutation in the RPEL-repeat domain abolished both the actin
      binding and the cell spreading activity. PP1-binding deficient mutants strongly
      induced cell retraction. Long and branched cytoplasmic processes were developed
      during the cell retraction. These results suggest that scapinin enhances cell
      spreading and motility through direct interaction with actin and that PP1 plays a
      regulatory role in scapinin-induced morphological changes.

PMID- 19158954
TI  - Nkx2.7 and Nkx2.5 function redundantly and are required for cardiac morphogenesis
      of zebrafish embryos.
AB  - BACKGROUND: Nkx2.7 is the tinman-related gene, as well as orthologs of Nkx2.5 and
      Nkx-2.3. Nkx2.7 and Nkx2.5 express in zebrafish heart fields of lateral plate
      mesoderm. The temporal and spatial expression patterns of Nkx2.7 are similar to
      those of Nkx2.5, but their functions during cardiogenesis remain unclear.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, Nkx2.7 is demonstrated to compensate for
      Nkx2.5 loss of function and play a predominant role in the lateral development of
      the heart, including normal cardiac looping and chamber formation. Knocking down
      Nkx2.5 showed that heart development was normal from 24 to 72 hpf. However, when
      knocking down either Nkx2.7 or Nkx2.5 together with Nkx2.7, it appeared that the
      heart failed to undergo looping and showed defective chambers, although embryos
      developed normally before the early heart tube stage. Decreased ventricular
      myocardium proliferation and defective myocardial differentiation appeared to
      result from late-stage up-regulation of bmp4, versican, tbx5 and tbx20, which
      were all expressed normally in hearts at an early stage. We also found that tbx5
      and tbx20 were modulated by Nkx2.7 through the heart maturation stage because an
      inducible overexpression of Nkx2.7 in the heart caused down-regulation of tbx5
      and tbx20. Although heart defects were induced by overexpression of an injection
      of 150-pg Nkx2.5 or 5-pg Nkx2.7 mRNA, either Nkx2.5 or Nkx2.7 mRNA rescued the
      defects induced by Nkx2.7-morpholino(MO) and Nkx2.5-MO with Nkx2.7-MO.
      CONCLUSIONS AND SIGNIFICANCE: Therefore, we conclude that redundant activities of
      Nkx2.5 and Nkx2.7 are required for cardiac morphogenesis, but that Nkx2.7 plays a
      more critical function, specifically indicated by the gain-of-function and loss
      of- function experiments where Nkx2.7 is observed to regulate the expressions of
      tbx5 and tbx20 through the maturation stage.

PMID- 19158955
TI  - The internally truncated LRP5 receptor presents a therapeutic target in breast
      cancer.
AB  - BACKGROUND: Breast cancer is a common malignant disease, which may be caused by a
      number of genes deregulated by genomic or epigenomic events. Deregulated WNT/beta
      catenin signaling with accumulation of beta-catenin is common in breast tumors,
      but mutations in WNT signaling pathway components have been rare. An aberrantly
      spliced internally truncated LRP5 receptor (LRP5Delta666-809, LRP5Delta) was
      shown recently to be resistant to DKK1 inhibition, and was required for beta
      catenin accumulation in hyperparathyroid tumors and parathyroid tumor growth.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we show, by reverse transcription PCR and
      Western blot analysis, that LRP5Delta is frequently expressed in breast tumors of
      different cancer stage (58-100%), including carcinoma in situ and metastatic
      carcinoma. LRP5Delta was required in MCF7 breast cancer cells for the non
      phosphorylated active beta-catenin level, transcription activity of beta-catenin,
      cell growth in vitro, and breast tumor growth in a xenograft SCID mouse model.
      WNT3 ligand, but not WNT1 and WNT3A augmented the endogenous beta-catenin
      activity of MCF7 cells in a DKK1-insensitive manner. Furthermore, an anti-LRP5
      antibody attenuated beta-catenin activity, inhibited cell growth, and induced
      apoptosis in LRP5Delta-positive MCF7 and T-47D breast cancer cells, but not in
      control cells. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the LRP5Delta
      receptor is strongly implicated in mammary gland tumorigenesis and that its
      aberrant expression present an early event during disease progression. LRP5
      antibody therapy may have a significant role in the treatment of breast cancer.

PMID- 19158956
TI  - Alteration of ocular surface mucins in MUC5AC-DTA transgenic mice.
AB  - PURPOSE: To investigate the compensation of secretory mucins with membranous
      mucins in mice with goblet cell deficiency. METHODS: A transgenic mouse model in
      which conjunctival goblet cells were targeted was generated, and the expression
      of mucins was evaluated through the toxicity of diphtheria toxin A driven by a
      human mucin, MUC5AC, promoter. Immunohistochemical staining, in situ
      hybridization, electronic microscopy, and quantitative reverse transcription
      polymerase chain reaction (RT-PCR) were used to characterize their phenotypes.
      RESULTS: The external appearance of the ocular surface was normal, and no corneal
      pathology was found. The quantity of MUC5AC and the number of conjunctival goblet
      cells decreased in this mouse as expected. However, the membranous mucin, MUC4,
      compensates the decrease of MUC5AC in terms of the results of immunohistochemical
      staining, in situ hybridization, electronic microscopy, and quantitative RT-PCR.
      CONCLUSIONS: The membranous mucin, MUC4, can compensate for the deficiency of the
      secretory mucin, MUC5AC, in goblet cell deficient mice. This compensation may
      explain why the symptoms of mucus threads can be found in some goblet deficiency
      diseases, and it may provide an alternative defensive mechanism in goblet cell
      deficiency.

PMID- 19158957
TI  - Overexpression of CERKL, a gene responsible for retinitis pigmentosa in humans,
      protects cells from apoptosis induced by oxidative stress.
AB  - PURPOSE: Retinitis pigmentosa (RP), a retinal neurodegenerative disorder
      characterized by apoptosis of photoreceptor cells, is caused by mutations in many
      different genes. We analyzed the RP gene ceramide kinase-like (CERKL) to
      determine CERKL function and contribution to pathogenesis. METHODS: RT-PCR was
      performed to characterize CERKL expression in many human adult and fetal tissues,
      including retina. We analyzed the protein subcellular localization by confocal
      microscopy and further verified it by sucrose gradients. We performed lipid
      kinase activity assays. And finally, we studied the effects on cell apoptosis
      after CERKL overexpression in transiently transfected cultured cells by propidium
      iodide staining and poly-(ADP-ribose)-polymerase (PARP) caspase-dependent
      cleavage. RESULTS: CERKL transcripts underwent alternative splicing. In the human
      retina, four different CERKL isoforms of 532, 558, 419, and 463 amino acids were
      expressed. CERKL proteins were mainly localized in the endoplasmic reticulum and
      Golgi compartments, but they also shifted localization to nuclei and nucleoli. We
      also found that CERKL prevented cells from entering apoptosis induced by
      oxidative-stress conditions. CONCLUSIONS: CERKL remains a unique orphan lipid
      kinase in that no candidate substrate has been identified after intense research.
      The dynamic localization of CERKL suggests multiple sites of action. Remarkably,
      CERKL (but not the RP R257X mutant) exerts a protective role in cells against
      oxidative stress, consistent with RP mutations impairing the normal protein
      function in photoreceptors and thus tilting the balance toward apoptosis. These
      results provide valuable insights into the molecular mechanisms causing retinal
      degeneration.

PMID- 19158958
TI  - Apoptosis induction by oxidized glycated LDL in human retinal capillary pericytes
      is independent of activation of MAPK signaling pathways.
AB  - BACKGROUND: Pericyte loss is a cardinal feature of early diabetic retinopathy. We
      previously reported that highly oxidized-glycated low density lipoprotein (HOG
      LDL) induces pericyte apoptosis in vitro. In this study, we investigated the role
      of the mitogen-activated protein kinase (MAPK) signaling pathways in HOG-LDL
      induced apoptosis in human pericytes. METHODS: Human retinal capillary pericytes
      (HRCP) were exposed to native LDL (N-LDL) and HOG-LDL, and apoptosis was measured
      using flow cytometry. Time- and dose-dependent responses of extracellular signal
      regulated kinase (ERK), p38, and Jun N-terminal kinase (JNK) following exposure
      to N-LDL or HOG-LDL were determined using western blotting. U0126 (ERK
      inhibitor), SB203580 (p38 inhibitor), and SP600125 (JNK inhibitor) were used to
      determine the role of MAPK signaling in HOG-LDL-induced apoptosis. RESULTS: HOG
      LDL induced apoptosis in HRCP in a dose-dependent manner at concentrations from 5
      to 50 mg/l, with a constant effect from 50 to 200 mg/l. When compared to serum
      free medium (SFM), this effect of HOG-LDL was found to be significant at all
      doses above 10 mg/l. In contrast, N-LDL at 200 mg/l did not induce apoptosis
      compared with SFM. Exposure to N-LDL versus HOG-LDL induced similar
      phosphorylation of ERK, p38, and JNK, peaking at 5 min, with similar dose
      dependent responses up to 25 mg/l that were constant from 25 to 100 mg/l.
      Blocking of the ERK, p38, and JNK pathways did not inhibit pericyte apoptosis
      induced by HOG-LDL. CONCLUSIONS: Our data suggest that apoptosis induced by HOG
      LDL in HRCP is independent of the activation of MAPK signaling pathways.

PMID- 19158959
TI  - Sequence alterations in RX in patients with microphthalmia, anophthalmia, and
      coloboma.
AB  - PURPOSE: Microphthalmia, anophthalmia, and coloboma are ocular malformations with
      a significant genetic component. Rx is a homeobox gene expressed early in the
      developing retina and is important in retinal cell fate specification as well as
      stem cell proliferation. We screened a group of 24 patients with microphthalmia,
      coloboma, and/or anophthalmia for RX mutations. METHODS: We used standard PCR and
      automated sequencing techniques to amplify and sequence each of the three RX
      exons. Patients' charts were reviewed for clinical information. The pathologic
      impact of the identified sequence variant was analyzed by computational methods
      using PolyPhen and PMut algorithms. RESULTS: In addition to the polymorphisms we
      identified a single patient with coloboma having a heterozygous nucleotide change
      (g.197G>C) in the first exon that results in a missense mutation of arginine to
      threonine at amino acid position 66 (R66T). In silico analysis predicted R66T to
      be a deleterious mutation. CONCLUSIONS: Sequence variations in RX are uncommon in
      patients with congenital ocular malformations, but may play a role in disease
      pathogenesis. We observed a missense mutation in RX in a patient with a small,
      typical chorioretinal coloboma, and postulate that the mutation is responsible
      for the patient's phenotype.

PMID- 19158960
TI  - Modulation of choroidal neovascularization by subretinal injection of retinal
      pigment epithelium and polystyrene microbeads.
AB  - PURPOSE: The study was conducted to create a rapidly developing and reproducible
      animal model of subretinal choroidal neovascularization (CNV) that allows a time
      dependent evaluation of growth dynamics, histopathologic features, and cytokine
      expression. METHODS: C57BL/6 and chemoattractant leukocyte protein-2 deficient
      (DeltaCcl-2) mice were studied. Mice received single or combined subretinal
      injections of cultured retinal pigment epithelium (RPE; C57BL/6-derived),
      polystyrene microbeads, or phosphate buffer solution (PBS). Fluorescence
      angiograms were performed over a period of 3 weeks. Mice were euthanized on post
      inoculation day 3, 7, 10, 14, or 21, and their eyes were evaluated by light,
      confocal, and electron microscopy. RESULTS: CNV membranes occurred in all study
      groups with an overall incidence of 94.3%. They extended in the subretinal space
      through central breaks in Bruch's membrane. CNV lesions were characterized by
      dynamic changes such as initiation, active inflammatory, and involution stages.
      CNV thickness peaked around PI day 7 and was greater in mice that received
      combined injections of RPE and microbeads or RPE cells alone. Small lesions
      developed in the control groups (microbeads or PBS only), in DeltaCcl-2, and old
      C57BL/6 mice. Variable expression of cytokines and growth factors was detected
      within the membranes. CONCLUSIONS: Our murine model represents a reliable
      approach inducing CNV growth by subretinal injection of either RPE cells alone or
      RPE cells and microbeads. The development of CNV lesions is a dynamic process
      that relies in part on macrophage trafficking and age.

PMID- 19158961
TI  - Sustained high quality of life in a 5-year long term follow-up after successful
      ablation for supra-ventricular tachycardia. results from a large retrospective
      patient cohort.
AB  - INTRODUCTION: The ablation of supraventricular tachycardias (SVT) using
      radiofrequency energy (RF) is a procedure with a high primary success rate.
      However, there is a scarcity of data regarding the long term outcome,
      particularly with respect to quality of life (QoL). METHODS AND RESULTS: In this
      retrospective single-center study, 454 patients who underwent ablation of SVT
      between 2002 and 2007 received a detailed questionnaire addressing matters of
      QoL. The questionnaire was a modified version of the SF-36 Health Survey
      questionnaire and the Symptom Checklist--Frequency and Severity Scale.After a
      mean follow up of 4.5+/-1.3 years, 309 (68.1%) of the contacted 454 patients (269
      female, 59.2%, mean age 58+/-6.5) completed the questionnaire. Despite of 27% of
      relapses in the study group, 91.7% considered the procedure a long-term success.
      The remainder of patients experienced no change in (3.7%) or worsening of (4.7%)
      symptoms. There were no significant differences between the various types of SVT
      (p=1). QoL in patients with Atrio-Ventricular Nodal Reentry Tachycardia (AVNRT)
      and Atrio-Ventricular Reentry Tachycardia (AVRT) improved significantly (p<0.0005
      respectively p<0.043), whereas QoL in patients with Ectopic Atrial Tachycardia
      (EAT) showed a non-significant trend towards improvement. Main symptoms before
      ablation, such as tachycardia (91.5%), increased incidence of tachycardia
      episodes over time (78.1%), anxiety (55.5%) and reduced physical capacity in
      daily life (52%) were significantly improved after ablation (p<0.0001).
      CONCLUSION: The high acute ablation success of SVT persists for years in long
      term follow up and translates into a significant improvement of QoL in most
      patients.

PMID- 19158963
TI  - S100 protein family and its application in clinical practice.
AB  - The members of the S100 protein family are multifunctional proteins with a
      regulatory role in a variety of cellular processes. They exert their actions
      usually through calcium binding, although Zn2+ and Cu2+ have also been shown to
      regulate their biological activity. The most studied member, protein S100B,
      exhibits neurotrophic (at physiologic concentration) or neurotoxic (at higher
      concentration) activity and its immunohistochemical expression or serum levels
      have been determined in various clinical disorders. S100B has been well
      documented as a marker of astrocytic activation mediating its effects via
      interaction with receptor for advanced glycation end products (RAGE). We herein
      provide a wide range of information concerning their clinical application in
      traumatic brain injuries, Alzheimer disease, subarachnoid haemorrhage and other
      neurologic disorders, malignant melanoma and several other neoplasms (as S100B
      has been shown to down-regulate p53), as well as inflammatory diseases. Also its
      use on predicting neurologic outcome after resuscitation for cardiac arrest or in
      intrauterine growth retardation newborns is discussed.

PMID- 19158962
TI  - Glutathione provides a source of cysteine essential for intracellular
      multiplication of Francisella tularensis.
AB  - Francisella tularensis is a highly infectious bacterium causing the zoonotic
      disease tularemia. Its ability to multiply and survive in macrophages is critical
      for its virulence. By screening a bank of HimarFT transposon mutants of the F.
      tularensis live vaccine strain (LVS) to isolate intracellular growth-deficient
      mutants, we selected one mutant in a gene encoding a putative gamma-glutamyl
      transpeptidase (GGT). This gene (FTL_0766) was hence designated ggt. The mutant
      strain showed impaired intracellular multiplication and was strongly attenuated
      for virulence in mice. Here we present evidence that the GGT activity of F.
      tularensis allows utilization of glutathione (GSH, gamma-glutamyl-cysteinyl
      glycine) and gamma-glutamyl-cysteine dipeptide as cysteine sources to ensure
      intracellular growth. This is the first demonstration of the essential role of a
      nutrient acquisition system in the intracellular multiplication of F. tularensis.
      GSH is the most abundant source of cysteine in the host cytosol. Thus, the
      capacity this intracellular bacterial pathogen has evolved to utilize the
      available GSH, as a source of cysteine in the host cytosol, constitutes a
      paradigm of bacteria-host adaptation.

PMID- 19158964
TI  - Current devices of respiratory physiotherapy.
AB  - In recent years patients with respiratory diseases use various devices, which
      help the removal of mucus from the airways and the improvement of pulmonary
      function. The aim of the present study is to determine the effectiveness of the
      current devices of respiratory physiotherapy, as it comes from the review of
      literature. The current devices of physiotherapy for patients with respiratory
      diseases, are presented as an alternative therapy method or a supplemental
      therapy and they can motivate patients to apply therapy by themselves. These
      devices seem to increase patients' compliance to daily treatment, because they
      present many benefits, as independent application, full control of therapy and
      easy use. These devices are the Positive Expiratory Pressure, the High Frequency
      Chest Wall Oscillation, the Oral High Frequency Oscillation, the Intrapulmonary
      Percussive Ventilation, the Incentive Spirometry the Flutter and the Acapella and
      the Cornet. Current devices seem to be effective in terms of mucus expectoration
      and pulmonary function improvement, as it is shown by published studies. The
      choice of the suitable device for each patient is a challenge for the
      physiotherapist in order to achieve better compliance in daily treatment. More
      controlled studies are needed due to the fact that the number of published
      studies is limited.

PMID- 19158965
TI  - Factors of cardiovascular risk in patients with type 2 diabetes and incipient
      nephropathy.
AB  - BACKGROUND: Microalbuminuria was originally established as a predictor of renal
      failure and an independent risk factor for cardiovascular disease in patients
      with diabetes mellitus as well as in general population. The aim of our study is
      to assess the relationship between microalbuminuria and the other risk factors in
      diabetics and their prevalence. METHODS: Sixty five patients, 22 men and 43 women
      with mean age 58.6+/-10.09, with type 2 diabetes, were hospitalized in the
      Department of Internal Medicine in the University Hospital Center "Mother Teresa"
      in Tirana, Albania, between March 2007 and February 2008. These patients with a
      mean duration of diabetes 6.09+/-5.41 were divided in two groups: with (Group A:
      24 patients) and without (Group B: 41 patients) microalbuminuria and each group
      was evaluated for left ventricular mass index (LVMI), body mass index (BMI),
      glycosylated hemoglobin (HbA1C), lipid profile and intima media thickness (IMT).
      RESULTS: The prevalence of microalbuminuria in our study was 32.3%. The
      prevalence of microalbuminuria in males was 37.5 and in females 62.5%. The
      microalbuminuric patients were older ( 59.71+/-9.87 vs 57.07+/-10.32) and had a
      longer duration of diabetes (7.74+/-5.74 vs 4.45+/-5.08) compared with
      normoalbuminuric patients (p=0.01). The Group A had significantly higher LVMI
      compared with Group B ( p=0.02). The prevalence of obesity (BMI>30 kg/m2) in our
      sample was 44.6%. In Group A the mean BMI (30.13+/-4.98) was significantly higher
      compared with Group B (28.00+/-3.72, p=0.04). Diabetic retinopathy was more
      frequent in Group A compared with Group B ( 33.3% vs 14.6%, p=0.05). The mean
      value of IMT was higher in Group A compared with Group B (1.28+/-0.35 vs 1.09+/
      0.28, p=0.03). CONCLUSION: In patients with type 2 diabetes and microalbuminuria
      LVMI, IMT, BMI, duration of diabetes was significantly higher compared with
      patients with type 2 diabetes and normoalbuminuria.

PMID- 19158966
TI  - The effect of intra-abdominal hypertension alone or combined intra-abdominal
      hypertension-endotoxemia in cerebral oxygenation in a porcine model.
AB  - BACKGROUND: Abdominal compartment syndrome (ACS) has been recognized as an
      entity, affecting cardiovascular, pulmonary, and cerebral function, while it is
      often complicated with sepsis. Goal of the study was the evaluation of brain
      oxygenation during ACS alone and in combination with endotoxinemia. MATERIALS AND
      METHODS: Sixteen pigs, undergone intra-abdominal hypertension, were allocated to
      receive intravenous administration of either saline or endotoxin. Pigs were
      evaluated regarding brain tissue oxygenation (PbrO2), systemic oxygenation (PaO2)
      and regional cerebral blood flow (rCBF). RESULTS: Statistical analysis revealed
      significant reduction of PbrO2 over time for sepsis group, after endotoxin
      administration. Regarding differences between groups, sepsis group experienced
      lower PbrO2 values, compared to saline group, only after endotoxin
      administration. Both groups experienced reduction in arterial oxygenation, with
      greater pertubations seen after sepsis induction. Regarding rCBF, septic pigs
      showed greater flow values, while ACS alone did not influence rCBF. ACS has no
      deleterious effects in cerebral oxygenation and flow, provided systemic
      oxygenation and CPP are maintained above normal value. CONCLUSIONS: Combined
      sepsis-ACS lead to perturbations in cerebral oxygenation, in conjunction with
      greater rCBF values. The latter could be ascribed to abnormalities in oxygen
      extraction.

PMID- 19158967
TI  - Detection of T cells secreting type 1 and type 2 cytokines in the peripheral
      blood of patients with oral lichen planus.
AB  - OBJECTIVE: The purpose of this study was to detect and enumerate T cells
      secreting type 1 and 2 cytokines in the peripheral blood of patients with oral
      lichen planus (OLP) and in healthy controls. SUBJECTS AND METHODS: The study
      group consisted of 80 OLP patients and 80 healthy individuals. Cytokine secreting
      T cells were detected using ELISPOT assay. RESULTS: There was a statistically
      significant decrease (p<0.05) in the number of IFN- and IL-12 secreting cells in
      the peripheral blood of patients with OLP compared to the controls. No
      statistical difference was observed in the number of IL-2 and TNF-a secreting
      cells between OLP patients and controls (p>0.05). Also there was no significant
      difference in the numbers of IFN-gamma, IL-12, IL-2 and TNF-a secreting cells
      between reticular and erosive forms of OLP (p>0.05). As regards type 2 cytokines,
      the number of IL-5 and IL-10 secreting cells was significantly decreased in OLP
      patients compared to the healthy control group (p<0.05). No statistical
      difference was observed in the number of IL-6 secreting cells between OLP
      patients and control group (p>0.05). Similarly, no statistical difference was
      observed in the number of IL-4 secreting cells between OLP patients and controls
      (p>0.05). No significant difference was also found in the numbers of IL-4, IL-5,
      IL-10 and IL-6 secreting cells between reticular and erosive OLP group.
      CONCLUSION: These data suggest decreased type 1 and type 2 cytokine production
      (except IL-4) in OLP patients.

PMID- 19158968
TI  - Biopsy of subcutaneus fatty tissue for diagnosis of systemic amyloidosis.
AB  - BACKGROUND: The diagnosis of systemic amyloidosis is determined through
      histological material from biopsy of different parenchymal organs, which have
      high diagnostic and informative value, but hide a high risk of bleeding because
      of the accumulation of amyloid in the vessels' wall. The main methods are kidney,
      liver, gastro-intestinal tract biopsy and aspiration of subcutaneous fatty
      tissue. The sensitivity of trans-dermal core kidney biopsy (KB) is close to 100%.
      The rectal biopsy is positive in 73% of cases, the biopsy of bone marrow in bout
      50% and the one of gingival mucosa in 40-46 % of cases. The biopsy of
      subcutaneous fatty tissue (BSFT) is a new, highly sensitive method with
      sensitivity 73% and specificity 90%, so that it can be used as a screening test
      in patients without any clinical symptom or organ dysfunction. PATIENTS AND
      METHODS: One hundred fifteen patients, 59 male and 56 female with an average age
      49.7+/-15.93 years were included in the study divided in two groups. The first
      group consisted of patients with kidney biopsy proved amyloidosis compared to
      biopsy findings from other parenchymal organs. The second group consisted of
      patients suspected having amyloidosis who underwent biopsies from various tissues
      or organs except kidney biopsy because there was contraindication. RESULTS: One
      hundred fifteen biopsies of subcutaneous fatty tissue (SFT) were performed for
      the diagnosis of systemic amyloidosis. In order to compare the data from the BSFT
      to the other known and practiced till the moment methods BSFT was performed in 54
      patients with proved amyloidosis by KB. In 51/54 the positive result for amyloid
      was confirmed. A comparison of the data in a sample of 20 patients, 11 female and
      9 male, in 18/20 patients the result from BSFT is positive (90%). In coloring
      with Congo red are typed with KMnO4 19/54 patients, 12 female and 7 male, with
      average age 48.12 (SD +/-13.21). In 14/19 the amyloidosis was typed as AA (74.2%)
      and 5/19 non-AA, probably AL (25.8%). To reveal the meaning of so called
      screening-biopsy of subcutaneous fatty tissue for excluding accompanying
      amyloidosis in patients with significant proteinuria and/or uremia,
      dysglobulinemia, laboratory constellations for nephritic syndrome in immune
      nephropathies and chronic infections (Chronic Obstructive Lung Disease, purulent
      infections) with contraindications for kidney biopsy 61 screening BSFT were
      performed, accumulation of amyloid was defined in 37. In all of the patients the
      result was verified also by biopsies of rectal, gingival and stomach mucosa.
      CONCLUSION: The purposeful searching and proving of amyloid in subcutaneous fatty
      tissue of the abdominal wall is a new, highly sensitive method. The receiving of
      richer material from SFT in the method "biopsy" in stead of "aspiration", makes
      it more reliable for proving amyloid in the case that it exists. The method is
      enough informative for proving not only amyloidosis AL, but also for amyloidosis
      AA, in treating with KMnO4. The biopsy of SFT in combination with biopsies from
      other mucosa can prove the accumulation of amyloid in contraindications for
      performing KB.

PMID- 19158969
TI  - Environmental risk factors for iron deficiency anemia in children 12-24 months
      old in the area of Thessalia in Greece.
AB  - BACKGROUND AND AIM: Iron deficiency anemia (IDA) is a common problem all over the
      world, which attacks mainly pregnant women, infants and children. The aim of the
      study was to estimate the prevalence of IDA in children 12-24 months old in a
      specific area of Thessalia, located in the central part of Greece, and to
      identify the environmental risk factors associated with it. PATIENTS AND METHODS:
      In the first part of this cross-sectional and case-control study, the hemoglobin
      (Hb) levels of 938 children were estimated by a mobile photometer analyzer. In
      the second part of the study, children with Hb<11 gr/dl were compared with
      matched random selected controls in hematological, anthropometric and
      environmental parameters. The estimated laboratory values were Hb, hematocrit,
      mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin
      concentration, zinc protoporphyrin, serum iron, serum ferritin, transferring
      saturation, total iron binding capacity and Hb electrophoresis. Finally 75
      children (34 boys, 41 girls, mean age 17.51+/-3.5 months), who were found with
      IDA, constituted the case group while 75 healthy children constituted the control
      group. RESULTS: The prevalence of IDA in the region was 7.99%. At the same time,
      a number of children with stigma of bthalassaemia (2.13%) was discovered,
      something that had escaped identification. There were no differences due to the
      method of determination (mobile or laboratory) in the values of Hb between the
      two groups. Significant differences were recorded (p<0.001) in all hematological
      and anthropometric parameters except for head circumference. Regarding
      environmental factors, significant differences were found in the following
      parameters: ratio rooms/number of family members (p=0.01), number of family
      members (p=0.01), number of children in the family (p<0.001), birth rate
      (p<0.001), education and profession of the parents (p<0.001), source of drinking
      water and sewage system (p<0.001), duration of breast feeding (p<0.001), milk
      consumption by the child during the period of the reported research (p<0.001),
      child's health status according to the mother (p<0.001), and frequency of seeking
      pediatric care (p=0.02). CONCLUSIONS: Although the prevalence of IDA in this area
      of Greece is similar to the one observed in the rest of the developed world, it
      still consists a public health problem. The mobile method for Hb estimation
      should be introduced in Greece since its reliability to detect IDA has been, once
      more, confirmed. The application of simple questionnaires for the detection of
      the environmental IDA risk factors could help in the prognosis and prevention of
      anemia. Further improvement of the IDA status in Greece could be achieved through
      the dissemination of information about iron rich foods, the amelioration of
      environmental conditions and the application of reliable, easy to use and cheap
      methods for Hb estimation.

PMID- 19158970
TI  - Alveolar soft-part sarcoma of the extremity: a case report.
AB  - Alveolar soft-part sarcoma (ASPS) is a rare form of soft tissue sarcoma and is
      most often seen in adolescents and young adults. Surgical excision of the primary
      tumor and pulmonary metastases has resulted in prolonged survival in some
      patients while the benefit of adjuvant chemotherapy and/or radiotherapy has been
      disputed. An 11- year-old boy with ASPS which presented with a markedly vascular
      tumor in the left thigh, and multiple bilateral pulmonary metastases 8 months
      after diagnosis is described. The patient has remained disease-free for over 5
      years since the initial diagnosis.

PMID- 19158971
TI  - Pain and osteolysis of the thoracic spine--a case of a rare monostotic fibrous
      dysplasia manifestation.
AB  - We describe a case of a young farmer from Central Macedonia, Greece suffering of
      a mild back pain more than one year. His medical history included
      hypercholesterolaemia (IIa type) and two episodes of spontaneous pneumothorax of
      unknown origin two and three years ago respectively. A full imaging survey
      revealed a single osteolytic lesion at the seventh thoracic vertebra. A CT guided
      needle biopsy was performed. Diagnosis based on clinical, imaging and
      histological findings was monostotic fibrous dysplasia of the thoracic spine. We
      discuss the clinical features and treatment of this non neoplastic condition
      which may simulate bone osteolytic tumor. Furthermore a possible correlation of
      concomitant conditions existing in our patient such as the metabolic disorder of
      hypercholesterolaemia and especially the history of spontaneous pneumothorax
      episodes with fibrous dysplasia within the spectrum of connective tissue disorder
      is discussed.

PMID- 19158972
TI  - 10-year trends in the diagnosis and treatment of hepatitis C and concomitant
      mental health disorders: 1995 to 2005.
AB  - OBJECTIVE: To evaluate trends in the rate and timing of treatment for hepatitis C
      in those with and without mental health comorbidities. METHOD: Data from the
      population-based Olmsted County Hepatitis C Registry in Minnesota were linked to
      patients' medical records to identify the dates and duration of any hepatitis C
      specific therapy as well as all diagnoses of mental health comorbid conditions
      prior to initiation of therapy. The most common mental health conditions, major
      depressive disorder, alcohol dependence, and intravenous drug use, were assessed
      separately. The registry includes all Olmsted County residents with a physician
      diagnosis of hepatitis C or non-A/non-B hepatitis (ICD-9 criteria) from January
      1, 1990, through December 31, 2005. RESULTS: The age-adjusted prevalence of
      diagnosed hepatitis C increased markedly between 1995 and 2000 (15.5/10,000
      persons to 27.0/10,000 persons) but changed little between 2000 and 2005 (27.0 to
      27.9/10,000 persons). The number of people with comorbid hepatitis C and
      depressive disorder (including minor depression) increased significantly between
      1995 and 2005 from 18% to over 35% of all people with diagnosed hepatitis C.
      Treatment rates more than doubled between 1995 and 2005, while the time from
      diagnosis to treatment decreased during that same period. By 2005, major
      depressive disorders were associated with a high rate of reasonably prompt
      treatment. There were no gender differences in treatment rates or time to
      treatment when other comorbidities and age were included in the analyses.
      CONCLUSIONS: From 1995 to 2005, rates of treatment for hepatitis C among people
      with and without comorbid mental health problems increased. Rates of increase
      were higher among those with depression and hepatitis C than among those with
      hepatitis C and drug abuse or other mental health diagnoses. Even with this
      progress in treating those with multiple diagnoses, over 75% of people with
      hepatitis C remain untreated.

PMID- 19158973
TI  - Relationship of somatic symptoms with depression severity, quality of life, and
      health resources utilization in patients with major depressive disorder seeking
      primary health care in Spain.
AB  - OBJECTIVE: To investigate the relationship between the characteristics of somatic
      symptoms and depression severity, quality of life (QOL), and health resources
      utilization in patients with major depressive disorder (MDD) in primary care
      setting. METHOD: This cross-sectional, nationwide epidemiologic study, carried
      out in 1150 primary care patients with DSM-IV-defined MDD, evaluated the
      characteristics of somatic symptoms by means of the Standardized Polyvalent
      Psychiatric Interview. Depression severity and QOL were evaluated by means of the
      Zung Self-Rating Depression Scale (SDS) and the Physical and Mental Component
      Summaries of the Medical Outcomes Study 12-item Short-Form Health Survey. Health
      resources utilization was measured in terms of doctor consultations and
      hospitalizations. The associations were assessed by means of adjusted analyses.
      The study was carried out from April 2004 to July 2004. RESULTS: Disability
      associated with somatic symptoms and number of somatic symptoms were strongly
      associated with increased depression severity (2.45 and 0.29 increase in SDS
      score, respectively) and health resources utilization (odds ratios of 1.42 and
      1.04, respectively). Associated disability, frequency, and persistence during
      leisure time of somatic symptoms were strongly associated with poorer QOL. In
      contrast, we found a weaker relationship between duration and intensity of
      somatic symptoms and depression severity, QOL, and health resources utilization.
      CONCLUSIONS: Of the studied somatic symptom characteristics, somatic symptom
      associated disability and number of somatic symptoms are strongly associated with
      increased depression severity and health resources utilization, as well as with
      decreased QOL. Our results may help physicians identify relevant characteristics
      of somatic symptoms to more effectively diagnose and treat depression in primary
      care patients.

PMID- 19158974
TI  - Long-term safety and tolerability of rivastigmine in patients with Alzheimer's
      disease switched from donepezil: an open-label extension study.
AB  - OBJECTIVES: The objective of this article is to present safety and tolerability
      data from the long-term extension phase of a core study conducted in patients
      with Alzheimer's disease (AD) who were immediately switched to rivastigmine.
      METHOD: This was a 26-week open-label extension (OLE) of a prospective, 26-week,
      open-label, single-arm, multicenter study conducted in the United States from
      October 2003 to January 2005. Patients had a diagnosis of Alzheimer's disease
      according to DSM-IV-TR and National Institute of Neurologic and Communicative
      Disorders and Stroke and the Alzheimer's Disease and Related Disorders
      Association criteria. Safety and tolerability of rivastigmine were monitored
      through monthly telephone contacts. At week 52, patients or caregivers were
      contacted by telephone to evaluate the patient's well-being. RESULTS: 146
      patients (approximately 79% of patients who completed the core phase) entered
      this OLE. Most patients (N = 115, 78.8%) completed the full 26 weeks of the
      extension phase, during which time they received a mean rivastigmine dosage of
      10.5 mg/day. The number of patients reporting newly occurring or worsening
      adverse events decreased considerably during the OLE (N = 84, 57.5%) compared
      with the core phase (the first 26 weeks; N = 116, 79.5%). Most patients reported
      adverse events that were mild or moderate in severity. At the end of the OLE, the
      majority of patients (128/146; 87.7%) were still receiving treatment with
      rivastigmine. At week 52, most caregivers expressed satisfaction with
      rivastigmine treatment (77.4%) and with the changes observed in the patient's
      behavior during the study (71.9%). CONCLUSIONS: For patients not tolerating or
      not responding to donepezil, treatment with rivastigmine was safe and well
      tolerated for at least 52 weeks.

PMID- 19158975
TI  - History of depressive and anxiety disorders and paroxetine response in patients
      with irritable bowel syndrome: post hoc analysis from a placebo-controlled study.
AB  - OBJECTIVE: Although irritable bowel syndrome (IBS) is highly comorbid with
      depressive and anxiety disorders, information on the clinical implications of
      this comorbidity is limited. We investigated whether a history of depressive
      and/or anxiety disorders was associated with response to treatment in a double
      blind, randomized, placebo-controlled trial of paroxetine controlled release (CR)
      in IBS. METHOD: Seventy-two IBS subjects (diagnosed using Rome II criteria) were
      recruited from August 2003 to November 2005 and randomly assigned to receive
      flexibly dosed paroxetine CR (dose, 12.5-50 mg/day) or placebo for 12 weeks. The
      Mini-International Neuropsychiatric Interview (MINI-Plus version) was used to
      ascertain current (exclusionary) or past diagnoses of depressive and anxiety
      disorders. Subjective depression, anxiety, and stress were assessed at entry and
      throughout the trial using the Beck Depression Inventory (BDI), Beck Anxiety
      Inventory (BAI), and Perceived Stress Scale (PSS). Severity of IBS symptoms was
      determined by the Composite Pain Score (CPS), administered via Interactive Voice
      Response System, and the Clinical Global Impressions scale (CGI). The primary
      outcome was treatment response defined as >= 25% reduction in CPS from
      randomization to end of treatment. A post hoc analysis (multivariate logistic
      regression) was done to evaluate whether a history of depressive and/or anxiety
      disorder was associated with response to medication. RESULTS: Baseline
      demographic and clinical characteristics (CPS, BDI, BAI, PSS, CGI scores) were
      similar between groups (history of depressive/anxiety disorder vs. no history).
      In multivariate logistic regression analysis, treatment response was not
      predicted by history of depressive and/or anxiety disorder (OR = 0.58, CI = 0.29
      to 1.68, p = .32) or drug status (paroxetine CR vs. placebo) (OR = 1.26, CI =
      0.68 to 3.21, p = .19). Drug status was significantly associated with the
      secondary outcome variable of treatment response as defined by a CGI improvement
      score of 1 to 2 (OR = 12.14, CI = 2.9 to 48.4, p < .001). Paroxetine CR was safe
      and well tolerated during the study. CONCLUSIONS: History of depressive and/or
      anxiety disorder was not associated with response of IBS symptoms to paroxetine
      CR. Conclusions are limited due to insufficient statistical power. Further
      research is needed to clarify the role of selective serotonin reuptake inhibitors
      in the treatment of IBS and to elucidate the treatment ramifications of comorbid
      psychiatric disorders. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00610909.

PMID- 19158977
TI  - Fitness to drive of psychiatric patients.
AB  - BACKGROUND: Driving a motor vehicle could be central to the functional autonomy
      of patients with psychiatric illnesses. For patients, a driver's license could
      mean independence, the ability to care for themselves, and the freedom to travel
      when they wish. However, both psychiatric disorders and psychiatric drug
      treatments can produce changes in perception, information processing and
      integration, and psychomotor activity that can disturb and/or interfere with the
      ability to drive safely. OBJECTIVE: To assess the fitness to drive of psychiatric
      outpatients in a sample representative of current clinical practice. METHOD:
      Cognitive functioning and psychomotor performance of 208 consecutive psychiatric
      outpatients treated in a community mental health center in the Canary Islands
      (Spain) were assessed in different clinical situations. The LNDETER 100 battery,
      an electronic assessment unit-based measurement that consists of 5 screenbased
      tests, was used to assess concentrated attention and resistance to monotony,
      multiple discriminative reactions and their correctness, anticipation of speed,
      bimanual coordination, and the decision making process and tendency to assume
      risk. The study was conducted from July 2007 to September 2007. RESULTS: Of 208
      patients, only 33 had scores compatible with the requirements of a driver's
      license, and 84% failed at least 1 of the required tests. Of patients with a
      driver's license who drive almost every day, 79.5% registered scores that would
      not allow obtaining or renewal of the license. None of the driving patients
      studied notified the traffic authorities that they had a psychiatric condition
      that may affect safe driving. No patient stopped driving, although 10% of them
      recognized that their ability to drive was somehow damaged. CONCLUSION: Guidance
      on how best to formulate and deliver recommendations on driving fitness in stable
      psychiatric patients is lacking and much needed.

PMID- 19158976
TI  - Chest pain and its importance in patients with panic disorder: an updated
      literature review.
AB  - CONTEXT: Chest pain is a common symptom in primary care settings, associated with
      considerable morbidity and health care utilization. Failure to recognize panic
      disorder as the source of chest pain leads to increased health care costs and
      inappropriate management. OBJECTIVE: To identify characteristics of the chest
      pain associated with the presence of panic disorder, review the consequences and
      possible mechanisms of chest pain in panic disorder, and discuss the recognition
      of panic disorder in patients presenting with chest pain. DATA SOURCES: Potential
      studies were identified via a computerized search of MEDLINE and PsycINFO
      databases and review of bibliographies. MeSH headings used included panic
      disorder with chest pain, panic disorder with coronary disease or cardiovascular
      disorders or heart disorders, and panic disorder with cholesterol or essential
      hypertension or tobacco smoking. STUDY SELECTION: The diagnosis of panic disorder
      in eligible studies was based on DSM criteria, and studies must have used
      objective criteria for coronary artery disease and risk factors. Only case
      control and cohort studies were included. DATA SYNTHESIS: Although numerous chest
      pain characteristics (believed to be both associated and not associated with
      coronary artery disease) have been reportedly linked to panic disorder, only
      nonanginal chest pain is consistently associated with panic disorder (relative
      risk = 2.03, 95% CI = 1.41 to 2.92). CONCLUSION: Chest pain during panic attacks
      is associated with increased health care utilization, poor quality of life, and
      phobic avoidance. Because the chest pain during panic attacks may be due to
      ischemia, the presence of panic attacks may go unrecognized. Ultimately, the
      diagnosis of panic disorder must be based on DSM criteria. However, once panic
      disorder is recognized, clinicians must remain open to the possibility of co
      occurring coronary artery disease.

PMID- 19158978
TI  - Easing the burden of bipolar disorder: from urgent situations to remission.

PMID- 19158979
TI  - Fear of medical illness: differential diagnosis, workup, and treatment.

PMID- 19158980
TI  - Diagnostic dilemma.

PMID- 19158981
TI  - Rolling rocks.

PMID- 19158982
TI  - Atypical Neuropsychiatric Presentation of Addison's Disease: A Case Report.

PMID- 19158983
TI  - Association of chronic fatigue syndrome and acute psychotic episode: is it
      coincidental?

PMID- 19158984
TI  - Low cholesterol, delinquency, and suicidality.

PMID- 19158985
TI  - Diagnosis of nonorganic monoplegia with single-pulse transcranial magnetic
      stimulation.

PMID- 19158987
TI  - Reexamining the Elderly Patient's Presentation With Depression.

PMID- 19158986
TI  - Rash and desquamation associated with risperidone oral solution.

PMID- 19158988
TI  - Free tyrosine and tyrosine-rich peptide-dependent superoxide generation catalyzed
      by a copper-binding, threonine-rich neurotoxic peptide derived from prion
      protein.
AB  - Previously, generation of superoxide anion (O(2)(*-)) catalyzed by Cu-binding
      peptides derived from human prion protein (model sequence for helical Cu-binding
      motif VNITKQHTVTTTT was most active) in the presence of catecholamines and
      related aromatic monoamines such as phenylethylamine and tyramine, has been
      reported [Kawano, T., Int J Biol Sci 2007; 3: 57-63]. The peptide sequence
      (corresponding to helix 2) tested here is known as threonine-rich neurotoxic
      peptide. In the present article, the redox behaviors of aromatic monoamines, 20
      amino acids and prion-derived tyrosine-rich peptide sequences were compared as
      putative targets of the oxidative reactions mediated with the threonine-rich
      prion-peptide. For detection of O(2)(*-), an O(2)(*-)-specific chemiluminescence
      probe, Cypridina luciferin analog was used. We found that an aromatic amino acid,
      tyrosine (structurally similar to tyramine) behaves as one of the best substrates
      for the O(2)(*-) generating reaction (conversion from hydrogen peroxide)
      catalyzed by Cu-bound prion helical peptide. Data suggested that phenolic moiety
      is required to be an active substrate while the presence of neither carboxyl
      group nor amino group was necessarily required. In addition to the action of free
      tyrosine, effect of two tyrosine-rich peptide sequences YYR and DYEDRYYRENMHR
      found in human prion corresponding to the tyrosine-rich region was tested as
      putative substrates for the threonine-rich neurotoxic peptide. YYR motif (found
      twice in the Y-rich region) showed 2- to 3-fold higher activity compared to free
      tyrosine. Comparison of Y-rich sequence consisted of 13 amino acids and its Y-to
      F substitution mutant sequence revealed that the tyrosine-residues on Y-rich
      peptide derived from prion may contribute to the higher production of O(2)(*-).
      These data suggest that the tyrosine residues on prion molecules could be
      additional targets of the prion-mediated reactions through intra- or inter
      molecular interactions. Lastly, possible mechanism of O(2)(*-) generation and the
      impacts of such self-redox events on the conformational changes in prion are
      discussed.

PMID- 19158991
TI  - Cortical neurons transgenic for human Abeta40 or Abeta42 have similar
      vulnerability to apoptosis despite their different amyloidogenic properties.
AB  - Alzheimer's disease (AD) is a leading cause of chronic dementia in the United
      States. Its incidence is increasing with an attendant increase in associated
      health care costs. Amyloid beta peptide (Abeta; a 39-42 amino acid molecule) is
      the major component of senile plaques, the hallmark lesion of AD. The toxic
      mechanism of Abeta peptides has not been well characterized. Specifically, the
      impact of Abeta1-40 (Abeta40) and its slightly longer counterpart fragment,
      Abeta1-42 (Abeta42), is not clearly understood. It has been suggested that, while
      Abeta40 might play a more physiologically relevant role, Abeta42 is likely the
      key amyloidogenic fragment leading to amyloid deposition in the form of plaques
      in AD, a pivotal process in Alzheimer's pathology. This notion was further
      supported by a recent study employing transgenic mouse models that expressed
      either Abeta40 or Abeta42 in the absence of human amyloid beta protein precursor
      (APP) overexpression. It was found that mice expressing Abeta42, but not Abeta40,
      developed compact amyloid plaques, congophilic amyloid angiopathy, and diffuse
      Abeta deposits. Since neuronal loss is one of the hallmark features in AD
      pathology, we hypothesize that cortical neurons from these two strains of
      transgenic mice for Abeta might show different vulnerability to cell death
      induced by classical inducers of apoptosis, such as trophic factor withdrawal
      (TFW). Contrary to our expectations, we found that, while overexpression of
      either Abeta40 or 42 significantly increased the vulnerability of primary
      cortical neurons to WFT-induced cell death, there was no significant difference
      between the two transgenic lines. Mitochondrial dysfunction, levels of oxidative
      stress, caspase activation and nuclear fragmentation are increased to about the
      same extent by both Abeta species in transgenic neurons. We conclude that Abeta40
      or Abeta42 induce similar levels of neurotoxicity following TFW in these
      transgenic mice despite the difference in their amyloidogenic properties.

PMID- 19158992
TI  - MDM2 expression and regulation in prostate cancer racial disparity.
AB  - MDM2 is a key negative regulator of tumor suppressor p53. A single nucleotide
      polymorphism in the MDM2 promoter, SNP309, enhances transcriptional activation of
      MDM2 and has been associated with early onset of several types of cancer. In this
      study, we attempted to determine if the MDM2 SNP309 polymorphism plays a role in
      the aggressive phenotype seen in African American (AA) prostate cancer by
      examining the association between MDM2 SNP309 and MDM2 protein levels in prostate
      cancer (PCa) patients of different racial backgrounds. Prospectively enrolled PCa
      patients (AA=51, CA=50) were evaluated for MDM2 SNP309 and MDM2 protein
      expression. MDM2 overexpression, defined as >10% of tumor cells in three tissue
      cores, was assessed using immunohistochemistry on tissue microarray. MDM2 protein
      expression was significantly greater in CA than AA patients (78% versus 45%
      respectively, p=0.0007). Germline DNA was analyzed by PCR-RFLP then confirmed by
      DNA sequencing. MDM2 SNP309 genotype frequencies did not differ significantly
      between AA and CA PCa patients (AA: TT 68.6%, TG 25.5%, GG 5.9%; CA: TT 62.0%, TG
      20.0%, GG 18.0%; p=0.16), suggesting that the MDM2 SNP309 allele does not play a
      significant role in the observed overexpression.

PMID- 19158990
TI  - High-grade prostatic intraepithelial neoplasia of the prostate: the precursor
      lesion of prostate cancer.
AB  - High-grade intraepithelial neoplasia (HGPIN) is a lesion which is widely believed
      to be a precursor of prostatic adenocarcinoma. Correct morphologic identification
      of HGPIN and an understanding of how this diagnosis affects clinical management
      in the research setting are necessary as HGPIN is a premalignant lesion with many
      genetic alterations similar to prostate cancer, but is not yet invasive cancer.
      As such it is critical to differentiate between benign entities, HGPIN, and
      prostatic adenocarcinoma for experimental design and data interpretation. This
      review discusses HGPIN, clarifies the terminology used in pathology reports, and
      describes the clinical and research implications of this entity.

PMID- 19158989
TI  - Epigenetics and epigenetic alterations in pancreatic cancer.
AB  - Pancreatic cancer remains a major therapeutic challenge. In 2008, there will be
      approximately 37,680 new cases and 34,290 deaths attributable to pancreatic
      cancer in the United States (U.S.), making it the fourth leading cause of cancer
      related death. Recent comprehensive pancreatic cancer genome project found that
      pancreatic adenocarcinomas harbored 63 intragenic mutations or
      amplifications/homozygous deletions and these alterations clustered in 12
      signaling pathways. In addition to widespread genetic alterations, it is now
      apparent that epigenetic mechanisms are also central to the evolution and
      progression of human cancers. Since epigenetic silencing processes are
      mitotically heritable, they can drive neoplastic progression and undergo the same
      selective pressure as genetic alterations. This review will describe recent
      developments in cancer epigenetics and their importance in our understanding of
      pancreatic adenocarcinomas.

PMID- 19158993
TI  - Developing a current awareness service using really simple syndication (RSS).

PMID- 19158994
TI  - Mapping the health research landscape in Sub-Saharan Africa: a study of trends in
      biomedical publications.

PMID- 19158995
TI  - Electronic document delivery; a six-year study to benchmark the shift to
      electronic interlibrary loan in two hospital libraries.

PMID- 19158997
TI  - Nursing educators' perceptions of collaboration with librarians.

PMID- 19158998
TI  - Why we need the Journal of the Medical Library Association.

PMID- 19158999
TI  - Analysis of the reporting of search strategies in Cochrane systematic reviews.
AB  - BACKGROUND: The Cochrane Handbook for Systematic Reviews of Interventions
      provides instructions for documenting a systematic review's electronic database
      search strategy, listing elements that should be in the description. Complete
      documentation of the search strategy allows readers to evaluate the search when
      critically appraising a review's quality. OBJECTIVE: The research analyzed
      recently published Cochrane reviews to determine whether instructions for
      describing electronic database search strategies were being followed. METHODS:
      Eighty-three new reviews added to the Cochrane Database of Systematic Reviews in
      the first quarter of 2006 were selected for analysis. Eighteen were subsequently
      excluded because their searches were conducted only in the specialized registers
      of Cochrane review groups. The remaining sixty-five reviews were analyzed for the
      seven elements of an electronic database search strategy description listed in
      the Cochrane Handbook, using dual review with consensus. RESULTS: Of the 65
      reviews analyzed, none included all 7 recommended elements. Four reviews (6%)
      included 6 elements. Thirty-two percent (21/65) included 5 or more elements, with
      68% (44/65) including 4 or fewer. Three included only 2 elements. The 65 reviews
      represented 41 different Cochrane review groups. CONCLUSION: The instructions
      from the Cochrane Handbook for reporting search strategies are not being
      consistently employed by groups producing Cochrane reviews.

PMID- 19159000
TI  - Volume 74 correction.

PMID- 19159001
TI  - Proceedings, 108th Annual Meeting Medical Library Association, Inc. Chicago, IL.
      May 16-21, 2008.

PMID- 19159002
TI  - "Partnering with Seniors for Better Health": computer use and Internet health
      information retrieval among older adults in a low socioeconomic community.
AB  - PURPOSE: This health communication project measured the psychosocial influences
      of computer anxiety, computer confidence, and computer self-efficacy in older
      adults at six meal congregate sites. The adults completed a five-week education
      intervention, based on Bandura's self-efficacy model, designed to assist older
      adults in retrieving and evaluating health information resources on the Internet.
      METHODS: One hundred thirty-seven participants, ages sixty-five and older, were
      randomized in a controlled, two-group, pre-post, repeated measures design.
      Participants in the intervention group received a two-hour training session, once
      a week for five weeks. The Computer Confidence Subscale and Computer Anxiety
      Subscale of the Computer Attitude Scale and the Computer Self-Efficacy Measure
      were administered to both groups at three time intervals: at baseline, completion
      of the five-week intervention, and six weeks after completion of the
      intervention. Data were analyzed using repeated measures analysis of variance.
      RESULTS: Findings showed a reduction in computer anxiety and increases in
      computer confidence and computer self-efficacy in retrieving and evaluating
      online health information (P<0.001). DISCUSSION: The study suggests an array of
      possibilities to engage older adults in the use of Internet health information
      resources to better contribute to their health, independence, safety, and
      wellness.

PMID- 19159003
TI  - Web 2.0 tools in medical and nursing school curricula.

PMID- 19159004
TI  - The Mobile Reference Service: a case study of an onsite reference service program
      at the School of Public Health.
AB  - The School of Public Health at Saint Louis University is located at a greater
      distance from the library than other programs on the main medical center campus.
      Physical distance diminishes the ease of access to direct reference services for
      public health users. To bridge the gap, the library developed the Mobile
      Reference Service to deliver on-site information assistance with regular office
      hours each week. Between September 2006 and April 2007, a total of 57 in-depth
      reference transactions took place over 25 weeks, averaging 2 transactions per
      week in a 2-hour period. Overall reference transactions from public health users
      went up 28%, while liaison contacts with public health users doubled compared to
      the same period the year before. The Mobile Reference Service program has
      improved library support for research and scholarship, cultivated and
      strengthened liaison relationships, and enhanced marketing and delivery of
      library resources and services to the Saint Louis University School of Public
      Health.

PMID- 19159005
TI  - Use of Facebook in academic health sciences libraries.

PMID- 19159006
TI  - The information-seeking behavior of clinical staff in a large health care
      organization.

PMID- 19159007
TI  - Status of open access in the biomedical field in 2005.
AB  - OBJECTIVES: This study was designed to document the state of open access (OA) in
      the biomedical field in 2005. METHODS: PubMed was used to collect bibliographic
      data on target articles published in 2005. PubMed, Google Scholar, Google, and
      OAIster were then used to establish the availability of free full text online for
      these publications. Articles were analyzed by type of OA, country, type of
      article, impact factor, publisher, and publishing model to provide insight into
      the current state of OA. RESULTS: Twenty-seven percent of all the articles were
      accessible as OA articles. More than 70% of the OA articles were provided through
      journal websites. Mid-rank commercial publishers often provided OA articles in OA
      journals, while society publishers tended to provide OA articles in the context
      of a traditional subscription model. The rate of OA articles available from the
      websites of individual authors or in institutional repositories was quite low.
      DISCUSSION/CONCLUSIONS: In 2005, OA in the biomedical field was achieved under an
      umbrella of existing scholarly communication systems. Typically, OA articles were
      published as part of subscription journals published by scholarly societies. OA
      journals published by BioMed Central contributed to a small portion of all OA
      articles.

PMID- 19159008
TI  - The Journey Project: a case study in providing health information to mitigate
      health disparities.
AB  - The Journey Project, part of the Virginia Commonwealth University Libraries'
      Social Work Information Specialist in Context Fellowship, was designed to merge
      social work and consumer health librarianship skills in order to improve the
      provision of health information to patients. A resource notebook was created
      encompassing the many dimensions of cancer health information. A social work
      informationist distributed the notebooks and provided individualized
      consultations with respect to patients' health information needs. Areas of
      congruence as well as key differences between social work and consumer health
      librarianship emerged during the course of the project. Merging the two
      professions into the role of a social work informationist increased the ability
      to attend holistically to clients' health information needs.

PMID- 19159009
TI  - Visceral leishmaniasis elimination programme in India, Bangladesh, and Nepal:
      reshaping the case finding/case management strategy.
AB  - OBJECTIVE: We sought to estimate visceral leishmaniasis (VL) burden in
      Bangladesh, India, and Nepal and document care-seeking behaviour for VL to
      provide baseline information for monitoring the VL elimination program and
      identify options for improved case finding and management. DESIGN: A cross
      sectional study using cluster sampling (clusters being villages) of 4 VL endemic
      districts was used in order to document all current and existing VL cases over
      the preceding 12 mo. Extended (in-depth) interviews were conducted in a subsample
      of households to explore (a) VL-related knowledge, attitudes, and practices of
      the population; (b) use of VL care by patients; and (c) delay between onset of
      symptoms, diagnosis, and start of treatment, as well as treatment interruption.
      Findings were discussed with national program managers and policy makers to
      develop improved strategies. RESULTS: Screening for VL was done in 18,933
      households (106,425 inhabitants). The estimated annual incidence of VL in the
      endemic districts was on average 22 times higher than the elimination target of
      less than one case per 10,000 inhabitants in 2015. This incidence varied widely
      between study sites, from 9.0 to 29.8 per 10,000 inhabitants. The percentage of
      newly detected cases through the household screening was high in the districts
      least covered by health-care services (particularly Rajshahi, Bangladesh, 49%;
      and to a lesser extent Vaishali in Bihar, India, 32.5%), and much lower in
      districts with greater availability of VL care (Muzaffarpur, India, 3.8%). On
      average 267 houses had to be visited, i.e., at least three to four working days
      per health worker, to identify a new VL (ranging from 1,432 houses in
      Muzaffarpur, India to only 166 houses in Rajshahi, Bangladesh). Knowledge of the
      disease and its vectors was good in India and Nepal but poor in Bangladesh
      (Rajshahi) where very little attention has been given to VL over the last
      decades. Although all socio-demographic indicators showed high levels of poverty,
      people in India preferred private medical practitioners for the treatment of VL,
      whereas in Nepal, and even more in Bangladesh, the public health-care sector was
      preferred. Delays between onset of symptoms and diagnosis as well as start of
      treatment was high. Reported non-adherence to treatment was particularly high in
      the more under-served districts and was mainly due to lack of resources.
      DISCUSSION: The findings suggest that (a) house-to-house screening may be useful
      in highly endemic districts with a poor passive case detection system, but
      further evidence on case finding adapted to local conditions has to be collected;
      (b) strengthening the quality of the public health sector is imperative in the
      three countries, especially in India, with its largely unregulated private-sector
      provision of VL care.

PMID- 19159010
TI  - Non-classical p38 map kinase functions: cell cycle checkpoints and survival.
AB  - The p38 MAPK kinase pathway is activated in response to a wide range of cellular
      stress stimuli and cytokines. Our understanding of the important functions of p38
      MAPK in the process of differentiation and cell death has grown considerably in
      the recent years and is now relatively established. Here we discuss the role of
      p38 MAPK in the mediation of cell cycle checkpoints and cell survival, processes
      that have received less attention. We describe how p38 MAPK regulates both the
      G2/M as well as a G1/S cell cycle checkpoint in response to cellular stress such
      as DNA damage. While p38 MAPK has classically been associated with the induction
      of apoptosis, we discuss that p38 MAPK can also mediate cell survival in specific
      situations, such as in response to DNA damage. It is important to recognize these
      less appreciated functions of p38 MAPK when considering the potential use of
      pharmacological inhibitors of p38 MAPK in therapeutic treatments for disease.

PMID- 19159011
TI  - Matrix metalloproteinase activity in pediatric acute lung injury.
AB  - Pediatric Acute Lung Injury (ALI) is associated with a high mortality and
      morbidity, and dysregulation of matrix metalloproteinases (MMPs) may play an
      important role in the pathogenesis and evolution of ALI. Here we examined MMP
      expression and activity in pediatric ALI compared with controls. MMP-8, -9, and
      to a lesser extent, MMP-2, -3, -11 and -12 were identified at higher levels in
      lung secretions of pediatric ALI patients compared with controls. Tissue
      Inhibitor of Matrix metalloproteinase-1 (TIMP-1), a natural inhibitor of MMPs was
      detected in most ALI samples, but MMP-9:TIMP-1 ratios were high relative to
      controls. In subjects who remained intubated for >or=10 days, MMP-9 activity
      decreased, with > 80% found in the latent form. In contrast, almost all MMP-8
      detected at later disease course was constitutively active. Discriminating MMP
      9:TIMP-1 ratios were found in those who had a prolonged ALI course. These results
      identify a specific repertoire of MMP isoforms in the lung secretions of
      pediatric ALI patients, and demonstrate inverse changes in MMPs -8 and -9 with
      protracted disease.

PMID- 19159012
TI  - Discovery of a non-peptidic inhibitor of west nile virus NS3 protease by high
      throughput docking.
AB  - BACKGROUND: The non-structural 3 protease (NS3pro) is an essential flaviviral
      enzyme and therefore one of the most promising targets for drug development
      against West Nile virus (WNV) and dengue infections. METHODOLOGY: In this work, a
      small-molecule inhibitor of the WNV NS3pro has been identified by automatic
      fragment-based docking of about 12000 compounds and testing by nuclear magnetic
      resonance (NMR) spectroscopy of only 22 molecules. Specific binding of the
      inhibitor into the active site of NS3pro and its binding mode are confirmed by
      15N-HSQC NMR spectra. The inhibitory activity is further validated by an
      enzymatic assay and a tryptophan fluorescence quenching assay. CONCLUSION: The
      inhibitor [4-(carbamimidoylsulfanylmethyl)-2,5-dimethylphenyl]
      methylsulfanylmethanimidamide has a good ratio of binding affinity versus
      molecular weight (ligand efficiency of 0.33 kcal/mol per non-hydrogen atom), and
      thus has good potential as lead compound for further development to combat West
      Nile virus infections.

PMID- 19159013
TI  - S100A7, a novel Alzheimer's disease biomarker with non-amyloidogenic alpha
      secretase activity acts via selective promotion of ADAM-10.
AB  - Alzheimer's disease (AD) is the most common cause of dementia among older people.
      At present, there is no cure for the disease and as of now there are no early
      diagnostic tests for AD. There is an urgency to develop a novel promising
      biomarker for early diagnosis of AD. Using surface-enhanced laser desorption
      ionization-mass spectrometry SELDI-(MS) proteomic technology, we identified and
      purified a novel 11.7-kDa metal- binding protein biomarker whose content is
      increased in the cerebrospinal fluid (CSF) and in the brain of AD dementia
      subjects as a function of clinical dementia. Following purification and protein
      sequence analysis, we identified and classified this biomarker as S100A7, a
      protein known to be involved in immune responses. Using an adenoviral-S100A7
      expression system, we continued to examine the potential role of S100A7 in AD
      amyloid neuropathology in in vitro model of AD. We found that the expression of
      exogenous S100A7 in primary cortico-hippocampal neuron cultures derived from
      Tg2576 transgenic embryos inhibits the generation of beta-amyloid (Abeta)(1-42)
      and Abeta(1-40) peptides, coincidental with a selective promotion of "non-
      amyloidogenic" alpha-secretase activity via promotion of ADAM (a disintegrin and
      metalloproteinase)-10. Finally, a selective expression of human S100A7 in the
      brain of transgenic mice results in significant promotion of alpha-secretase
      activity. Our study for the first time suggests that S100A7 may be a novel
      biomarker of AD dementia and supports the hypothesis that promotion of S100A7
      expression in the brain may selectively promote alpha-secretase activity in the
      brain of AD precluding the generation of amyloidogenic peptides. If in the future
      we find that S1000A7 protein content in CSF is sensitive to drug intervention
      experimentally and eventually in the clinical setting, S100A7 might be developed
      as novel surrogate index (biomarker) of therapeutic efficacy in the
      characterization of novel drug agents for the treatment of AD.

PMID- 19159014
TI  - A novel replication-competent vaccinia vector MVTT is superior to MVA for
      inducing high levels of neutralizing antibody via mucosal vaccination.
AB  - Mucosal vaccination offers great advantage for inducing protective immune
      response to prevent viral transmission and dissemination. Here, we report our
      findings of a head-to-head comparison of two viral vectors modified vaccinia
      Ankara (MVA) and a novel replication-competent modified vaccinia Tian Tan (MVTT)
      for inducing neutralizing antibodies (Nabs) via intramuscular and mucosal
      vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which
      was historically used as a smallpox vaccine for millions of Chinese people. The
      spike glycoprotein (S) of SARS-CoV was used as the test antigen after the S gene
      was constructed in the identical genomic location of two vectors to generate
      vaccine candidates MVTT-S and MVA-S. Using identical doses, MVTT-S induced lower
      levels ( approximately 2-3-fold) of anti- SARS-CoV neutralizing antibodies (Nabs)
      than MVA-S through intramuscular inoculation. MVTT-S, however, was capable of
      inducing consistently 20-to-100-fold higher levels of Nabs than MVA-S when
      inoculated via either intranasal or intraoral routes. These levels of MVTT-S
      induced Nab responses were substantially (approximately 10-fold) higher than that
      induced via the intramuscular route in the same experiments. Moreover, pre
      exposure to the wild-type VTT via intranasal or intraoral route impaired the Nab
      response via the same routes of MVTT-S vaccination probably due to the pre
      existing anti-VTT Nab response. The efficacy of intranasal or intraoral
      vaccination, however, was still 20-to-50-fold better than intramuscular
      inoculation despite the subcutaneous pre-exposure to wild-type VTT. Our data have
      implications for people who maintain low levels of anti-VTT Nabs after historical
      smallpox vaccination. MVTT is therefore an attractive live viral vector for
      mucosal vaccination.

PMID- 19159015
TI  - Taste, a new incentive to switch to (R)-praziquantel in schistosomiasis
      treatment.
AB  - BACKGROUND: Praziquantel (PZQ) is the drug compound of choice in the control and
      treatment of schistosomiasis. PZQ is administered as a racemate, i. e. 1ratio1
      mixture of enantiomers. The schistosomicidal activity arises from one PZQ
      enantiomer, whereas the other enantiomer does not contribute to the activity. The
      WHO's Special Programme for Research and Training in Tropical Diseases (TDR) has
      assigned the low-cost preparation of pure schistosomicidal (-)-PZQ a key priority
      for future R&D on PZQ, but so far this transition has not happened. PZQ has two
      major administration drawbacks, the first being the high dose needed, and its
      well documented bitter and disgusting taste. Attempts of taste-masking by low
      cost means have not been successful. We hypothesized that the non
      schistosomicidal component in PZQ would be the main contributor to the unpleasant
      taste of the drug. If the hypothesis was confirmed, the two major administration
      drawbacks of PZQ, the high dose needed and its bitter taste, could be addressed
      in one go by removing the component contributing to the bitter taste. METHODS AND
      FINDINGS: PZQ was separated into its schistosomicidal and the non
      schistosomicidal component, the absolute stereochemical configuration of (-)-PZQ
      was determined to be (R)-PZQ by X-ray crystallography, and the extent of
      bitterness was determined for regular racemic PZQ and the schistosomicidal
      component in a taste study in humans. FINDING: The schistosomicidal component
      alone is significantly less bitter than regular, racemic PZQ. CONCLUSION: Our
      hypothesis is confirmed. We propose to use only the pure schistosomicidal
      component of PZQ, offering the advantage of halving the dose and expectedly
      improving the compliance due to the removal of the bitter taste. Therefore, (R)
      PZQ should be specifically suitable for the treatment of school-age children
      against schistosomiasis. With this finding, we would like to offer an additional
      incentive to the TDR's recommendation to switch to the pure schistosomicidal (R)
      PZQ.

PMID- 19159016
TI  - SpolvlgA is a DDX3/PL10-related DEAD-box RNA helicase expressed in blastomeres
      and embryonic cells in planarian embryonic development.
AB  - Planarian flatworms have an impressive regenerative power. Although their
      embryonic development is still poorly studied and is highly derived it still
      displays some simple characteristics. We have identified SpolvlgA, a Schmidtea
      polychroa homolog of the DDX3/PL10 DEAD-box RNA helicase DjvlgA from the
      planarian species Dugesia japonica. This gene has been previously described as
      being expressed in planarian adult stem cells (neoblasts), as well as the germ
      line. Here we present the expression pattern of SpolvlgA in developing embryos of
      S. polychroa and show that it is expressed from the first cleavage rounds in
      blastomere cells and blastomere-derived embryonic cells. These cells are
      undifferentiated cells that engage in a massive wave of differentiation during
      stage 5 of development. SpolvlgA expression highlights this wave of
      differentiation, where nearly all previous structures are substituted by
      blastomere-derived embryonic cells. In late stages of development SpolvlgA is
      expressed in most proliferating and differentiating cells. Thus, SpolvlgA is a
      gene expressed in planarian embryos from the first stages of development and a
      good marker for the zygote-derived cell lineage in these embryos. Expression in
      adult worms is also monitored and is found in the planarian germ line, where it
      is showed to be expressed in spermatogonia, spermatocytes and differentiating
      spermatids.

PMID- 19159018
TI  - Editorial: Clinically relevant, scientifically based.

PMID- 19159017
TI  - STAT2*C related genotypes and allele but not TLR4 and CD40 gene polymorphisms are
      associated with higher susceptibility for asthma.
AB  - OBJECTIVE: Asthma is caused by a complex interaction between multiple genes and
      environmental factors. Herein we aimed to investigate whether signal transducer
      and activator of transcription (STAT2), toll-like receptors 4 (TLRs4) and CD40
      related polymorphisms are associated with asthma susceptibility. DESIGN: Children
      were divided: (1) asthma (n=117); (2) normal controls (n=60). The polymorphisms
      of STAT2, TLR4 and CD40 polymorphism were analyzed by PCR-RFLP genotyping.
      Genotypes, allelic frequencies and association of haplotypes in both groups were
      compared. RESULTS: STAT2*C related genotypes, but not TLR4 and CD40 polymorphism,
      are associated with higher susceptibility for asthma. Distributions of
      STAT2*CC/CG/GG and C/G allele in both groups are: (1) 0/11.1/88.9 % and
      5.6/94.4%; (2) 0/1.7/98.3% and 0.8/99.2% (p<0.05). Proportions of TLR4*rs10983755
      AA/AG/GG and rs1927914 CC/CT/TT homozygote are: (1) 35.1/8.5/56.4% and
      9.4/56.4/34.2%; (2) 35/8.3/56.7% and 16.7/48.3/35% (non-difference). Proportions
      of CD40*rs1883832 CC/CT/TT, rs3765459 AA/AG/GG, and rs4810485 TT/GT/GG are: (1)
      29.9/53/17.1%, 6.8/47.9/45.3 and 18.8/62.4/18.8%; (2) 36.7/41.7/21.6%, 1.6/46.7/
      51.7 and 15/51.7/33.3% (non-difference). Haplotype analyses for TLR4 and CD40
      genes revealed their non-association and non-additional effect upon asthma
      susceptibilities. CONCLUSION: STAT2*C related genotypes and alleles are
      associated with asthma susceptibilities and pathogenesis. There were non
      association and non-additional effects of TLR4/CD40 gene polymorphisms and
      haplotypes upon asthma risk.

PMID- 19159019
TI  - Odontogenic sinus tracts: a cohort study.
AB  - OBJECTIVE: To determine the prevalence,location, and distribution of sinus tracts
      in patients referred for endodontic consultation. METHOD AND MATERIALS: This
      cohort study included 1,119 subjects referred for endodontic consultation, 108 of
      whom presented with sinus tracts. Following clinical and radiographic
      examination, the diameter of the rarifying osteitis lesion on the radiograph was
      measured and the path and origin of the sinus tracts determined. Signs and
      symptoms, tooth site,buccal/lingual location, and diameter were recorded. Data
      were statistically analyzed using Pearson chi-square test. RESULTS: Sinus tracts
      originated mainly from maxillary teeth (63.1%); only 38.9% originated from
      mandibular teeth. Chronic periapical abscess was the most prevalent diagnosed
      origin (71.0%). Broken restorations were highly associated with the presence of
      sinus tracts (53.0%). The most frequent site of orifices was buccal(82.4%),
      followed by lingual or palatal (12.0%). Orifices on the lingual aspect of the
      gingiva were observed in mandibularmolars. There was an 86.8% correlation between
      the occurrence of an apically located sinus tract and apical rarifying
      osteitis(P<.01). CONCLUSION: Sinus tract in the lingual or palatal aspect of the
      gingiva is relatively common. Practitioners should look for signs of sinus tract
      during routine examination

PMID- 19159020
TI  - Complex all-ceramic rehabilitation of a young patient with a severely compromised
      dentition: a case report.
AB  - A young patient with dentinogenesisimperfecta and a dentition severely
      compromised by discolorations,abrasion, and breakage of enamel on several teeth
      was prosthodontically treated with CAD/CAM-manufactured all-ceramic restorations.
      To reduce treatment risk, preparations were limited paragingivally. Maxillary
      anterior teeth and premolars were restored with adhesively luted ceramic crowns.
      All other teeth were treated with zirconia-based restorations luted with a self
      etching resin-based material. Considering the deficient pretreatment situation,
      the use of tooth-colored restoration and luting materials yielded a satisfying
      functional and good esthetic result. The patient is highly satisfied, even though
      3 minor chippings occurred shortly after the completion of treatment

PMID- 19159021
TI  - Local application of tetracycline solution with a microbrush: an alternative
      treatment for persistent periodontitis.
AB  - OBJECTIVE: Topical antibiotics may overcome shortcomings of mechanical therapy
      for localized persistent periodontitis. This double-center, single-blind,
      randomized controlled study aimed to evaluate the microbiologic profile and
      clinical parameters of persistent periodontal pockets after treatment with
      tetracycline solution. METHOD AND MATERIALS: Thirty-seven patients who had at
      least 4 non-adjacent sites of persistent periodontal pockets with probing depth
      of at least 5 mm and bleeding on probing were randomly assigned to test and
      control groups. In the test group, 2 teeth received 4 applications of
      tetracycline solution (100 mg/mL) with a microbrush(T), while the other 2 teeth
      received the same treatment plus 1 session of scaling and root planing(SRP+T). In
      the control group, 2 teeth received 1 session of scaling and root planing(SRP),
      and the other 2 teeth received 4 applications of saline with a microbrush plus 1
      session of scaling and root planing(SRP+S). Clinical parameters of probing depth,
      bleeding on probing, visible plaque index, gingival bleeding index, gingival
      recession, as well as clinical attachment level and subgingival plaque samples
      (evaluated by polymerase chain reaction) were measured at baseline and 1, 3, and
      6 months. RESULTS: All therapies yielded statistically significant data on
      clinical measurements with no significant differences among groups. Presence of
      bacteria decreased in both groups, but only in the test group was a significant
      decrease of Porphyromonasgingivalis,Tannerellaforsythia, and
      Actinobacillusactinomycetemcomitans noted up to 6 months. CONCLUSION:
      Tetracycline applied with a microbrush may be an alternative treatment for
      persistent periodontitis that can probably be mediated by reduction of
      microorganism proliferation

PMID- 19159022
TI  - Primary oral malignant melanoma--a case report and review of the literature.
AB  - Malignant melanoma is a neoplasm of melanocytic origin that arises from a benign
      melanocytic lesion or de novo from melanocytes within otherwise normal mucosa or
      skin. Melanoma arising from the mucosal surfaces of the head and neck is a very
      rare disease and is considered among the most deadly of all human neoplasms.
      Although it comprises 1.3% of all cancers, malignant melanoma of the oral cavity
      accounts for only 0.2% to 8.0% of all reported melanomas. Because most mucosal
      melanotic lesions are painless in their early stages, the diagnosis is
      unfortunately often delayed until symptoms resulting from ulceration or growth
      are noted. Oral malignant melanoma has an extremely poor prognosis. For
      prevention of oral mucosal melanomas, any solitary pigmentation that has no
      obvious explanation should be always biopsied. The case of a 40-year-old man with
      primary malignant melanoma of the maxillary gingiva is reported

PMID- 19159023
TI  - Pigmentation susceptibility of teeth after bleaching with 2 systems: an in vitro
      study.
AB  - OBJECTIVE: To determine the susceptibility of teeth to darken after bleaching
      with 35% hydrogen peroxide and 16%carbamideperoxide. METHOD AND MATERIALS: Thirty
      eight premolars were covered with varnish and the mesiobuccal facets polished up
      to 0.04 microm, leaving a flat surface. Thirty-six of these premolars were then
      randomly assigned to 3 groups and the shade of the polished surfaces recorded
      using a Vita shade guide set in a value disposition. According to the
      manufacturers'instructions, 12 samples were bleached with 35% hydrogen peroxide
      (in-office group) and 12 samples with 16%carbamide peroxide (at-home group). The
      12 samples in the control group were not bleached. Two days later, the shades of
      the bleached teeth were recorded; all samples were immersed in silver nitrate 50%
      for 4 hours,rinsed, and fixed (using a dithioxamidesolution) for 24 hours.
      Polished surfaces were cleaned and the samples' shade recorded and analyzed using
      ANOVA. The remaining 2 premolars were bleached the same as those in the test
      group and analyzed using atomic force microscopy. RESULTS: The mean shade values
      were 6.2, 3.7, and 10.9 for in-office samples; 8.8, 1.7, and 6.1 for at-home
      samples; and 7.8 and 9.4 for the control group. After pigmentation, the at-home
      group had a lighter shade than the in-office group (P=or<.001). Atomic force
      microscopy showed no significant surface differences. CONCLUSION: While all the
      samples were susceptible to pigmentation, this tendency was greater following
      application of 35% hydrogen peroxide

PMID- 19159024
TI  - Prevalence of Actinobacillus actinomycetemcomitans in Chinese chronic
      periodontitis patients and periodontally healthy adults.
AB  - OBJECTIVE: Actinobacillusactinomycetemcomitans is a major periodontal pathogen.
      This research was aimed at investigating the prevalence of A
      actinomycetemcomitans in Chinese chronic periodontitis patients and periodontally
      healthy adults. METHOD AND MATERIALS: A total of 116 chronic periodontitis
      patients and 111 periodontally healthy adults were included. In each
      periodontitispatient,subgingival plaque samples were collected from 2 molar sites
      with the deepest pockets and 1 periodontally healthy site. The samples of
      periodontally healthy adults were obtained from the mesiobuccal site of 1
      maxillary first molar. A actinomycetemcomitans was detected by 16S rRNA
      polymerase chain action. Pocket depth, clinical attachment loss, and bleeding on
      probing of the sampled sites were recorded. RESULTS: A actinomycetemcomitans was
      detected in only 1 site (0.90%) of periodontally healthy subjects. For chronic
      periodontitispatients, the prevalence of periodontitis sites (33.62%) was
      significantly higher than that of healthy sites (0.90%)(P<.05); the occurrence
      showed a decreasing trend as patient age increased: highest in the 20- to 35-year
      old group (44.12%), followed by the 36- to 55-year-old group (36.36%) and 56- to
      75-year-old group (22.73%)(P<.05). A actinomycetemcomitans was most frequently
      detected in sites with pocket depth 7 mm or more and clinical attachment loss 6
      mm or more (P<.05) and more often detected in sites that exhibited bleeding on
      probing (37.07%) than those that did not (7.41%)(P<.05). CONCLUSIONS: A
      actinmycetemcomitans was more frequently detected in periodontitis sites than in
      periodontally healthy sites. For chronic periodontitispatients, a higher
      prevalence was associated with the severe sites than moderate and mild sites. A
      actinomycetemcomitans is considered to be a major pathogen in the etiology of
      chronic periodontitis

PMID- 19159025
TI  - Odontomas: a clinicopathologic study in a Portuguese population.
AB  - OBJECTIVE: Odontoma is a tumorlike malformation (hamartoma) that contains
      odontogenic epithelium with odontogenicectomesenchyme. Frequency and distribution
      of odontogenic tumor among a Portuguese population were analyzed and compared
      with previous reports. METHOD AND MATERIALS: A total of 65 odontogenic tumor
      cases were collected from the files of the Department of Pathology of Hospital
      Sao Joao,Porto,Portugal, and the Institute of Molecular Pathology and Immunology
      of the University of Porto (IPATIMUP), from January 1993 to December 2006. Of
      these cases, 48 were retrieved and analyzed. The final diagnosis of each case was
      based on the 2005 WHO histopathologic classification of odontogenictumors, and to
      the authors' best knowledge, the present series represents the first study on
      odontomas in a northern Portuguese population. RESULTS: Of the 65 odontogenic
      tumors cases, 64 (98.5%) were benign and 1 (1.5%), an ameloblasticcarcinoma, was
      malignant. Odontoma was the most frequent odontogenic tumor (73.9%), followed by
      unicysticameloblastoma(7.7%) and calcifying cystic odontogenic tumor (7.7%). Of
      the 48 odontomas(26 males and 22 females), 34 (70.8%) were compound and 14
      (29.2%) were complex. Most odontomas(72.9%) occurred in patients under the age of
      30, with a peak incidence in the second decade of life. Twenty-eight
      (58.3%)odontomas were in the maxilla and 20 (41.7%) in the mandible (P<.05).
      Twenty-eight (58.3%) of the 48 odontomas were associated with 33 impacted teeth,
      including 31 permanent teeth, 1 primary tooth, and 1 supernumerary tooth. The
      maxillary central incisor (n= 6; 19.4%) and the maxillary canine (n= 6; 19.4%)
      were most commonly associated with odontoma, followed by the mandibular canine
      (n= 5; 16.0%) and maxillary third molar (n= 4; 12.9%). CONCLUSION: This study
      provides clinical and pathological information on odotogenic tumors in a nothern
      Portuguese population

PMID- 19159026
TI  - Efficacy of dental practitioners in injection techniques: computerized device and
      traditional syringe.
AB  - OBJECTIVE: To compare the effect of clinicians on the behavioral pain reaction of
      children who received local anesthesia with a conventional technique and a
      computerized device (Wand, Milestone Scientific). METHOD AND MATERIALS: One
      hundred four children aged 6 to 12 years who needed operative dentistry using
      infiltrative anesthesia in the mandible and maxilla were selected for this study.
      The patients were divided into 2 groups, each assigned to a different clinician,
      and received anesthesia either by the Wand or conventional technique. Two
      experienced pediatric dentists performed all injections. During the injection,
      the modified behavioral pain scale was used for objective evaluation of the
      children. RESULTS: Chi-square analysis revealed no statistically significant
      difference in the behavior of children when receiving the Wand or conventional
      technique within each dentist and between dentists (P>.05). CONCLUSION: There
      seemed to be no difference in perceived pain between the Wand and conventional
      injection performed by experienced clinicians in school-age children

PMID- 19159027
TI  - Intraoral lipomas: a study of 26 cases in a Brazilian population.
AB  - OBJECTIVE: To analyze the clinical and histopathologic features of all cases
      diagnosed as lipomas in the oral cavity in a Brazilian population. METHOD AND
      MATERIALS: From 2002 to 2006, 26 cases of intraoral lipoma were studied. Clinical
      features obtained from biopsy records and microscopic slides were reviewed
      according to the World Health Organization and other cases previously described.
      RESULTS: Mean age was 54.6 years (range, 29 to 91 years) with predilection for
      women. The buccal mucosa was the most common location (n= 9), followed by the
      tongue (n= 7), lower lip (n= 4), floor of the mouth (n= 3), retro-molar area (n=
      2), and buccalsulcus(n= 1).Histologically, the lesions were defined as classic
      lipomas(n= 15),fibrolipomas(n= 7), intramuscular lipoma(n= 2), spindle-cell
      lipoma(n= 1), and sialolipoma(n= 1). Follow-up information was available in 20
      cases. No case recurred during a 6- to 12-month period. CONCLUSION: The benign
      nature of intraoral lipomas is supported by its bland histopathologic appearance
      and the absence of recurrences following complete local excision

PMID- 19159028
TI  - Radiographic diagnostics: Keratocyst of the left mandible.

PMID- 19159029
TI  - Medical education in a flat world.

PMID- 19159030
TI  - Assessment of psychometric properties of a modified PHEEM questionnaire.
AB  - BACKGROUND: An effective tool in analysing the learning environment, customised
      to the Sri Lankan setting, is vital for the assessment and delivery of quality
      healthcare training of preregistration house officers. Such a tool should be
      reliable and valid. We assessed psychometric properties such as internal
      reliability and construct validity of a modified version of the Postgraduate
      Hospital Educational Environment Measure (PHEEM). MATERIALS AND METHODS: A
      modified PHEEM questionnaire customised to the Sri Lankan context was developed
      in accordance to the Sri Lanka Medical Council guidelines. The questionnaire was
      distributed to all interns at the National Hospital of Sri Lanka, Colombo North
      Teaching Hospital and Wathupitiwala Base Hospital during a calendar year (n =
      100, response rate = 86%). Internal reliability and construct validity of the
      inventory were assessed by using Cronbach's alpha and exploratory factor analysis
      respectively as statistical methods. RESULTS: PHEEM consists of 3 subscales:
      perceptions of autonomy, social support and teaching, which are factors perceived
      to be influencing the educational environment. This administration demonstrated
      high internal reliability as reflected by a Cronbach's alpha value of 0.84.
      Exploratory factor analysis identified 12 factors with eigenvalue >1. However,
      the first factor had an eigenvalue of 6.7 (accounting for 19.7% of variance),
      while the rest had eigenvalues < 2.5. These results suggest a single predictive
      factor and thus a one-dimensional scale as opposed to the three-dimensional scale
      which is used in the current questionnaire. CONCLUSIONS: The psychometric
      properties of this tool reflect a high degree of internal reliability in
      assessing the educational environment of intern doctors in Sri Lanka. It is
      possible that the clinical educational environment is collectively represented as
      a single dimension. This may be due to the complex interplay between individual
      items in the questionnaire. Therefore the psychometric properties do not justify
      the interpretation of the educational environment through specified subscales.

PMID- 19159031
TI  - Use of knowledge-sharing web-based portal in gross and microscopic anatomy.
AB  - INTRODUCTION: Changes in worldwide healthcare delivery require review of current
      medical school curricula structure to develop learning outcomes that ensures
      mastery of knowledge and clinical competency. In the last 3 years, Mayo Medical
      School implemented outcomes-based curriculum to encompass new graduate outcomes.
      MATERIALS AND METHODS: Standard courses were replaced by 6-week clinically
      integrated didactic blocks separated by student-self selected academic enrichment
      activities. Gross and microscopic anatomy was integrated with radiology and
      genetics respectively. Laboratory components include virtual microscopy and
      anatomical dissection. Students assigned to teams utilise computer portals to
      share learning experiences. High-resolution computed tomographic (CT) scans of
      cadavers prior to dissection were made available for correlative learning between
      the cadaveric material and radiologic images. RESULTS: Students work in teams on
      assigned presentations that include histology, cell and molecular biology,
      genetics and genomic using the Nexus Portal, based on DrupalEd, to share their
      observations, reflections and dissection findings. CONCLUSIONS: New generation of
      medical students are clearly comfortable utilising web-based programmes that
      maximise their learning potential of conceptually difficult and labor intensive
      courses. Team-based learning approach emphasising the use of knowledge-sharing
      computer portals maximises opportunities for students to master their knowledge
      and improve cognitive skills to ensure clinical competency.

PMID- 19159032
TI  - The learning of 7th year medical students at internal medical--evaluation by
      logbooks.
AB  - INTRODUCTION: The purpose of this study was to understand the learning of
      internal medicine of 7th year medical students through records of the "Learning
      Passport". MATERIALS AND METHODS: Between June 2005 and June 2006, data from the
      learning passport (a type of logbook) of 207 7th year medical students at the
      Department of Internal Medicine, National Taiwan University Hospital (NTUH) were
      collected. RESULTS: Among the 19 symptoms/signs listed in the logbook, a large
      number of students did not learn well on low back pain, skin rash, oedema,
      oliguria and anxiety/depression; only a few students rated themselves as
      knowledgeable about anxiety/depression, malaise, skin rash, headache and
      anorexia. Among the 16 diseases listed, a large number of students did not learn
      well on chronic obstructive pulmonary disease, stroke, hypertension, coronary
      artery disease and cirrhosis; only a few students rated themselves as
      knowledgeable about shock, respiratory failure, consciousness disturbance, sepsis
      and renal failure. Among the 21 physical examination skills listed, a large
      number of students did not learn well on the male genitalia, eyes, cognitive
      status, mental state and the digital rectal examination; only a few students
      rated themselves as fully competent about cognitive status, mental state, eyes,
      neurology examination and ENT examination. Among the 11 laboratory skills and
      image interpretation skills listed, a large number of students did not learn well
      on blood smear, Gram's stain and specimen sampling; only a few students rated
      themselves as fully competent about the interpretation of brain computed
      tomographic (CT) scan, blood smear and Gram's stain. Among the 12 procedures and
      therapeutic skills listed, a large number of students did not learn well on
      observation of lumbar puncture, basic cardiopulmonary resuscitation (CPR) and
      aseptic procedure; only a few students rated themselves as fully competent about
      basic CPR and transfusion management. CONCLUSIONS: The weak points of intern
      training conducted by the Department of Internal Medicine, NTUH were revealed by
      analysis obtained from their logbooks. Thus, we need to strengthen the learning
      of the interns in these specific parts and assess their performance based on the
      use of portfolios.

PMID- 19159033
TI  - Implementation and evaluation by formal assessments and term end student feedback
      of a new methodology of clinical teaching in surgery in small group sessions.
AB  - The existing clinical teaching in small group sessions is focused on the
      patient's disease. The main dual limitation is that not only does the clinical
      skill testing become secondary but there is also a slackening of student
      involvement as only 1 student is evaluated during the entire session. A new
      methodology of small group teaching being experimented shifted the focus to
      testing students' clinical skills with emphasise on team participation by daily
      evaluation of the entire team. The procedure involved was that the group
      underwent training sessions where the clinical skills were taught demonstrated
      and practiced on simulated patients (hear-see-do module). Later the entire small
      group, as a team, examined the patient and each student was evaluated for 1 of 5
      specific tasks--history taking, general examination, systemic examination,
      discussion and case write-up. Out of 170 students, 69 students (study) and 101
      students (control) were randomly chosen and trained according to the new and
      existing methods respectively. Senior faculty (who were blinded as to which
      method of teaching the student underwent) evaluated all the students. The marks
      obtained at 2 examinations were tabulated and compared for tests of significance
      using t-test. The difference in the marks obtained showed a statistically
      significant improvement in the study group indicating that the new module was an
      effective methodology of teaching. The teaching effectiveness was evaluated by
      student feedback regarding improvement in knowledge, clinical and communication
      skills and positive attitudes on a 5-point Likert scale. Psychometric analysis
      was very positively indicative of the success of the module.

PMID- 19159034
TI  - A survey of medical students' perceptions of the quality of their medical
      education upon graduation.
AB  - INTRODUCTION: To evaluate the perceptions of the graduates of our medical school
      regarding the quality of their educational programme. MATERIALS AND METHODS: A
      total of 183 questionnaires, each containing 262 questions, were completed
      anonymously by medical students upon their graduation from the medical school.
      RESULTS: About 77% of the respondents felt that Basic Science courses lacked
      clinical relevance. Many of the students (61.2%) believed that physiology,
      amongst other Basic Science courses, was the most clinically relevant course.
      Assessment of the students about their clinical clerkship and internship
      rotations was not very favourable. Overall only 28.4% of the respondents were
      generally satisfied with the medical training they received. Respondents
      indicated many deficiencies in the curriculum, and in their competences. Exposure
      to numerous activities was rated by respondents as being inadequate: "geriatrics
      and gerontology education" (87.5%), "office management" (86.4%), "alternative
      medicine" (85.8%), "healthcare quality improvement" (85.7%), and "rehabilitation"
      (83%). Around 70% of the respondents reported that they have not been taught
      sufficient clinical skills in preparations for their future clinical practice.
      Only 33.3% of the respondents felt that they had acquired adequate knowledge and
      skills to start residency training. CONCLUSIONS: This study illuminates many
      aspects of the curriculum the faculty needs to address in order to prepare
      physicians effectively and efficiently for clinical work. It can be used as a
      tool to find the trends in our curriculum and the impact of curriculum revision
      activities which are currently underway in our School of Medicine.

PMID- 19159035
TI  - Does team learning motivate students' engagement in an evidence-based medicine
      course?
AB  - INTRODUCTION: Small group-based instructional methods such as team learning have
      been shown to produce positive educational outcomes. To motivate students'
      learning in an evidence-based medicine course, we explore team learning as a
      teaching strategy, and describe students' engagement and preference for this mode
      of learning. MATERIALS AND METHODS: An adaptation of team learning was
      implemented in September 2007 for all Year 2 Medical undergraduates attending the
      Principles in Evidence-Based Medicine course at the National University of
      Singapore. First, each student attempted a multiple-choice question individually.
      Next, the student discussed the same question with his/her team and provided a
      group response. Individual and group answers were recorded using keypads and
      Turning Point software. Students' engagement and preference for team learning
      were measured using a self-reported Likert Scale instrument. The pattern of
      engagement in team learning was compared with conventional tutorial involving the
      same cohort of students using chi2 trend test. RESULTS: A total of 224 (88%) and
      215 (84%) students responded to the surveys on team learning and conventional
      tutorial respectively. Overall, students reported a higher level of engagement
      with team learning than conventional tutorial. However, regardless of the mode of
      instruction, the students were equally likely to pay attention in class. Sixty
      nine per cent of students found team learning more enjoyable than conventional
      tutorial, with 73% preferring this mode of learning. There was a tendency for the
      percentage of correct responses to improve after group discussion. CONCLUSIONS:
      Team learning is the preferred mode of learning by Year 2 students attending the
      evidence-based medicine course. It promoted a high level of students' engagement
      and interaction in class.

PMID- 19159036
TI  - Step-2 Thai Medical Licensing Examination result: a follow-up study.
AB  - INTRODUCTION: The Thai medical students sat for the Medical Licensing Examination
      of Thailand (MLET) Step 2 for the first time in 2008. This paper analysed the
      first batch of Ramathibodi students taking the MLET Steps 1 and 2 in 2006 and
      2008 respectively. MATERIALS AND METHODS: The scores from the MLET Steps1 and 2,
      and fifth-year cumulative grade point averages (GPAX) of 108 students were
      analysed. RESULTS: Only 6 (5.6%) students failed the MLET Step 2 examination.
      Students who failed the MLET Step1 were more likely to fail their MLET Step 2
      (relative risk, 5.8; 95% confidence interval, 1.3-26.0). Students with low GPAX
      or scoring in the lowest quintile or tertile on the MLET Step1 were also at
      increased risk of failing the LET Step 2. CONCLUSIONS: The data suggest that
      performance on the MLET Step 1 and GPAX are important predictors of a student's
      chances of passing the MLET Step 2. Students with poor academic achievement or
      failing the MLET Step1 should be given intensive tutorials to pass the medical
      licensing examination.

PMID- 19159037
TI  - Development of a tool to evaluate health science students' experiences of an
      interprofessional education (IPE) programme.
AB  - INTRODUCTION: The Rural Interprofessional Programme Emergency Retreat (RIPPER) is
      an educational programme collaboratively developed and evaluated by an
      interprofessional team from Schools within Faculty of Health Science (FHS),
      University of Tasmania (UTAS), Australia. The aims of RIPPER are to foster and
      facilitate positive and productive interprofessional learning experiences for
      undergraduate students in a rural setting; and to develop a firmly embedded and
      sustainable interprofessional healthcare module within the health science
      curriculum. This paper reports on the development of a reliable and valid survey
      tool to evaluate students' understandings and experiences of this
      interprofessional learning programme. MATERIALS AND METHODS: Twenty-nine students
      from the Schools of Nursing, Medicine and Pharmacy of the FHS, UTAS participated
      in the RIPPER programme which offers a number of interactive rural emergency
      healthcare scenarios using high- and low-fidelity simulation. To evaluate the
      programme a survey which consisted of 2 main components was developed and
      implemented before and after the programme. The first component was designed to
      gather students' demographic information, their understanding of the
      interprofessional practice concepts, and their expectations of the RIPPER
      programme using open-ended questions. The second component consisted of a 5-point
      Likert scale for students to rank their level of agreement pre- and post-
      intervention with 12 statements about team working, programme evaluation and
      collaborative learning. Three processes were used to establish the validity and
      reliability of the survey. Content validity was assessed by academics and experts
      in health science education. Construct validity was assessed using exploratory
      factor analysis. The internal consistency and reliability of the survey was
      checked using Cronbach's alpha coefficient. RESULTS: Factor analysis of the 12
      statements identified 3 main factors including appreciation of professional roles
      and responsibilities, improved professional practice based on effective teamwork
      and the importance of students learning and working together for improved
      clinical practice. Reliability of the survey was established. The survey is able
      to evaluate students' understandings and experiences of this interprofessional
      learning programme.

PMID- 19159038
TI  - Supporting learners who are studying or training using a second
      language:preventing problems and maximising potential.
AB  - INTRODUCTION: This paper looks at the barriers to effective postgraduate study
      potentially experienced by learners in the United Kingdom if their first language
      is not English. As part of the internationalisation of higher education, we are
      seeing a welcome increase in students leaving their home country to study. This
      brings benefits to both home and visiting students as they learn more about each
      other and come to understand differences and build on aspects they have in
      common. However it also brings specific challenges of linguistic capability,
      differences in cultural expectations of the role of learners and teachers and in
      the understanding of the nature of postgraduate study. English medium higher
      education institutions worldwide are increasingly engaged in development of
      courses on English for academic purposes, or for academic writing. There is even
      a Journal of English for Academic Purposes, with co-editors from Hong Kong and
      the UK. Previous research has tended to concentrate on teacher-centred issues
      such as maintaining the integrity of assessments (including a focus on
      inadvertent plagiarism), practical aspects such as familiarity and expertise with
      information technology and more recently an understanding that acculturation has
      a part to play in maximising the success of students moving from one country's
      academic model to another. MATERIALS AND METHODS: This was a qualitative project
      during which students whose first language was not English were interviewed.
      Thirteen postgraduate students on a masters award in medical education were
      engaged in semi structured interviews to elicit their experiences, views and
      suggestions. RESULTS: Three themes emerged as important to the students in this
      study: understanding and being understood is not just due to the words we use;
      the nature of postgraduate study is not universal; and the need to maintain
      personal identity.

PMID- 19159039
TI  - Quality management of medical education at the Carl Gustav Carus Faculty of
      Medicine, University of Technology Dresden, Germany.
AB  - The Carl Gustav Carus Faculty of Medicine, University of Technology Dresden,
      Germany, was founded in 1993 after the reunification of Germany. In 1999, a
      reform process of medical education was started together with Harvard Medical
      International. The traditional teacher and discipline-centred curriculum was
      replaced by a student-centred, interdisciplinary and integrative curriculum which
      has been named DIPOL (Dresden Integrative Patient/Problem- Oriented Learning).
      The reform process was accompanied and supported by a parallel-ongoing Faculty
      Development Program. In 2004, a Quality Management Program in medical education
      was implemented, and in 2005 medical education received DIN EN ISO 9001:2000
      certification. Quality Management Program and DIN EN ISO 9001:2000 certification
      were/are unique for the 34 medical schools in Germany. The students played a very
      important strategic role in all processes. They were/are members in all
      committees like the Faculty Board, the Board of Study Affairs (with equal
      representation) and the ongoing audits in the Quality Management Program.
      Students are the only ones who experience all years of the curriculum and are
      capable of detecting, for example gaps, overlaps, inconsistencies of the
      curriculum and assessments. Therefore, the in-depth knowledge of students about
      the medical school's curriculum is a very helpful and essential tool in
      curriculum reform processes and Quality Management Programs of medical education.
      The reform in medical education, the establishment of the Quality Management
      program and the certification resulted in an improvement of quality and output of
      medical education and medical research.

PMID- 19159040
TI  - World Federation for Medical Education Policy on international recognition of
      medical schools' programme.
AB  - The increasing globalisation of medicine, as manifested in the migration rate of
      medical doctors and in the growth of cross-border education providers, has
      inflicted a wave of quality assurance efforts in medical education, and
      underlined the need for definition of standards and for introduction of effective
      and transparent accreditation systems. In 2004, reflecting the importance of the
      interface between medical education and the healthcare delivery sector, a World
      Health Organization (WHO)/World Federation for Medical Education (WFME) Strategic
      Partnership to improve medical education was formed. In 2005, the partnership
      published Guidelines for Accreditation of Basic Medical Education. The WHO/WFME
      Guidelines recommend the establishment of proper accreditation systems that are
      effective, independent, transparent and based on medical education-specific
      criteria. An important prerequisite for this development was the WFME Global
      Standards programme, initiated in 1997 and widely endorsed. The standards are now
      being used in all 6 WHO/WFME regions as a basis for quality improvement of
      medical education throughout its continuum and as a template for national and
      regional accreditation standards. Promotion of national accreditation systems
      will have a pivotal influence on future international appraisal of medical
      education. Information about accreditation status - the agencies involved and the
      criteria and procedure used - will be an essential component of new Global
      Directories of Health Professions Educational Institutions. According to an
      agreement between the WHO and the University of Copenhagen (UC), these
      Directories (the Avicenna Directories) will be developed and published by the UC
      with the assistance of the WFME, starting with renewal of the WHO World Directory
      of Medical Schools, and sequentially expanding to cover educational institutions
      for other health professions. The Directories will be a foundation for
      international meta-recognition ("accrediting the accreditors") of educational
      institutions and their programmes.

PMID- 19159041
TI  - A systems approach to teach core topics across graduate medical education
      programmes.
AB  - INTRODUCTION: Core curricula including Ethics, Medico-legal issues,
      Socioeconomics, and Quality Improvement (QI) are relevant and significant for
      graduate medical education programmes, regardless of specialty. A lack of faculty
      expertise in these content areas is a frequently cited concern among specialty
      programmes in graduate medical education. We report the results of an
      institutional systems-approach to assist this challenge. Our institution has 86
      post-graduate residency and fellowship training programmes serving 1068 learners.
      Directors of these programmes expressed the need for a centralised approach to
      teach learners about insurance systems and the basics of QI. MATERIALS AND
      METHODS: Two subject matter experts in the fields of insurance systems and 1
      expert in QI conducted 2 institution-wide didactics on each of the content areas,
      attended by 192 and 225 learners respectively. RESULTS: Significant improvement
      in learner knowledge was noted for all 3 knowledge-based questions for both
      content areas (P <0.0001). Learner self-assessment of knowledge of insurance
      systems increased from a pre-session mean of 2.86 to a post-session mean of 3.80
      (P <0.0001) and from 3.29 to a post-session mean of 4.17 (P <0.0001) for the QI
      didactics. CONCLUSION: Systems-wide didactic sessions for learners of different
      residencies has several advantages including the efficient use of content
      experts, prevention of resource burnout, and cost effectiveness. This strategy
      may also assist programmes directors in meeting external accreditation
      requirements.

PMID- 19159042
TI  - Graduate public health education--Singapore's contribution to strengthening
      capacity in the region and beyond.
AB  - The year 2008 marks the 55th anniversary of the graduate public health programme
      in Singapore. This article traces the evolution of the programme-from the Diploma
      in Public Health in 1953 to the Master of Public Health in 2007--in response to
      changing challenges and needs. It also discusses the role Singapore can continue
      to play in addressing global inequities in access to public health education and
      in strengthening public health capacity in the region and beyond.

PMID- 19159043
TI  - Harnessing the IT factor in medical education.
AB  - Escalating healthcare costs in Singapore have produced a significant movement of
      patients into ambulatory care, and the consequent dearth of clinical teaching
      materials. This deficiency has likewise prompted the creation of ambulatory
      teaching clinics and the use of standardised patients and simulators. In the last
      few decades, educators have utilised digital technology, for instance, digitally
      recorded heart and breath sounds, and digitised video vignettes, in medical
      education. We describe several pedagogical initiatives that we have undertaken at
      our university school of medicine.

PMID- 19159044
TI  - Towards a global educational matrix for tomorrow's health systems.

PMID- 19159045
TI  - The effect of acute rhinosinusitis on pulmonary function in adults.
AB  - OBJECTIVE: To evaluate the influence of acute rhinosinusitis on lung function as
      measured by spirometry. METHOD: An observational study in Danish general practice
      on 25 adult patients with a clinical diagnosis of acute rhinosinusitis and
      without any signs of chronic lung disease or allergy. Patients performed
      spirometry at the initial acute visit and then eight weeks later when the
      rhinosinusitis had resolved. RESULTS: Eight weeks after the initial visit there
      was a significant increase in the maximum mid-expiratory flow (F25-75), and in
      peak flow. CONCLUSION: Acute rhinosinusitis in adults without any sign of chronic
      lung disease or allergy is accompanied by a temporary reduction in maximum mid
      expiratory flow and peak flow. This may be caused by subclinical inflammation in
      the airways during acute rhinosinusitis. Further studies with extended lung
      function measurements are needed to evaluate and confirm this finding.

PMID- 19159046
TI  - Does telehealthcare offer a patient-centred way forward for the community-based
      management of long-term respiratory disease?

PMID- 19159047
TI  - [Do we still need DSA for clarification of peripheral arterial disease?].

PMID- 19159049
TI  - Copper toxicity in leaves of Elodea canadensis Michx.
AB  - Elodea canadensis (Canadian waterweed) has an ability to accumulate and
      bioconcentrate heavy metals. In this work, selected cellular responses for Cu
      treatment were studied in leaves of E. canadensis. Short term experiments, i.e. 1
      week exposure to 0.5, 1, 5, and 10 microM of Cu indicated that concentrations up
      to 10 microM Cu causes a pronounced accumulation of photosynthetic pigments, a
      drastic degradation of soluble proteins with molecular weight above 18 kDa and a
      rapid accumulation of polypeptides with molecular weight below 14 kDa. The
      connection of these observations with copper detoxification mechanisms in aquatic
      macrophytes are discussed.

PMID- 19159050
TI  - Effects of acute exposure to metribuzin on some hematological, biochemical and
      histopathological parameters of common carp (Cyprinus carpio L.).
AB  - The aim of the study was to evaluate acute toxic effects of the preparation
      Sencor 70 WG (metribuzin 70% W/V) on hematological, biochemical indices and
      histology of the common carp (Cyprinus carpio L.). In carp exposed for 96 h to
      Sencor 70 WG in the concentration of 250.2 mg/L, showed significantly lower
      (p<0.01) values of plasma total proteins, albumins, total globulins,
      triacylglycerols, lactate dehydrogenase, lactate, inorganic phosphate,
      hematocrit, hemoglobin concentration, mean erythrocyte volume, the leucocrite
      value, lymphocyte, and significantly higher (p<0.01) values of glucose, ammonia,
      calcium, monocytes, neutrophile granulocytes, developmental forms myeloid
      sequence and basophiles compared to the control group. Histopathological
      examination revealed hyaline degeneration of the epithelial cells of renal
      tubules of the caudal kidney. This alteration of kidney resulted in
      hypoproteinemia, followed by generation of transudate in body cavity.

PMID- 19159051
TI  - Acute toxicity and hazard assessment of spinosad and R-11 to three cladoceran
      species and Coho salmon.
AB  - Acute toxicity data and hazard assessments were developed for three cladoceran
      species, Ceriodaphnia dubia, Daphnia pulex, and Daphnia magna, and juvenile Coho
      salmon, Oncorhynchus kisutch after exposure to the insecticide, spinosad and
      adjuvant R-11. The effect of a mixture of these compounds was also determined
      with C. dubia and O. kisutch. Spinosad was virtually non-toxic to O. kisutch.
      Hazard assessments indicated that R-11 posed no hazard to any of the species
      tested while spinosad only posed a hazard to C. dubia. Mixture studies indicated
      that spinosad and R-11 may interact synergistically in C. dubia.

PMID- 19159052
TI  - Studies on the residue of hydrogen cyanamide in grape berries.
AB  - Multilocational field trials were conducted in grapevines at four different
      locations by applying hydrogen cyanamide 50% SL during 2006-2007. In order to
      determine the residue of hydrogen cyanamide in grape, hydrogen cyanamide 50% SL
      was applied to the freshly pruned grapevines at the rate of 1.20% a.i./L, 2.40%
      a.i./L, 4.80% a.i./L along with untreated control. No residue was detected in
      grape berries at the time of harvest irrespective of any locations.

PMID- 19159053
TI  - Rapid method for multi-residue determination of avermectins in bovine liver using
      high-performance liquid chromatography with fluorescence detection.
AB  - A simple method using high-performance liquid chromatography and fluorescence
      detection is presented for the simultaneous determination of the antiparasitic
      agents avermectins (abamectin, ivermectin and doramectin) in bovine liver.
      Samples were extracted using acetonitrile and cleaned up on an alumina SPE column
      and derivatized with trifluoroacetic anhydride. The derivatives were detected
      using fluorescence detector set at 365 nm excitation and 475 nm emission
      wavelengths. As the results, the limit of quantification for three avermectins
      was about 1 microg/kg. Inter-assay showed the mean recoveries of avermectins in
      bovine liver ranged from 72% to 81%, with RSD less than 9.9%.

PMID- 19159054
TI  - Rectovaginal fistulography: a technique for the identification of recurrent
      elusive fistulas.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of this study is to review our
      experience with a technique for diagnosing small rectovaginal fistulas that
      occasionally permit passage of air or mucus. METHODS: During an in-office visit
      suspicious areas of the vagina were probed with a cone-tip catheter and injected
      with a contrast dye to visualize the suspected fistula tract communicating to the
      rectum under fluoroscopic guidance. The fistulous tracts were further isolated
      using a flexi-tip glide wire. RESULTS: Five out of nine patients were found to
      have fistulas not diagnosed by other means. Three patients had recurrent
      rectovaginal fistula after a vaginal delivery, one patient was identified with a
      high rectovaginal fistula due to diverticular disease, and one patient had a
      rectovaginal fistula due to prior hemorrhoidectomy. One patient had a negative
      test, and the fistula that was diagnosed intraoperatively was due to underlying
      Crohn's disease. CONCLUSION: Direct fistulography is a useful technique to
      visualize otherwise elusive symptomatic rectovaginal fistula tracts.

PMID- 19159055
TI  - Bilateral extraperitoneal uterosacral vaginal vault suspension: a 2-year follow
      up longitudinal case series of 123 patients.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study is to assess anatomical
      and functional results of the extraperitoneal uterosacral ligament suspension
      (USL) in women with post-hysterectomy vaginal vault prolapse. METHODS: One
      hundred and twenty-three consecutive women were included. Concurrent procedures
      were anterior colporraphy with fascial repair (20%) and mesh reinforcement (49%),
      posterior colporraphy with fascial repair (38%) and mesh reinforcement (56%) and
      a sling procedure (29%). Women were assessed using Baden and Walker and pelvic
      organ prolapse quantification classification pre- and post-operatively. RESULTS:
      One hundred and ten patients (89%) were available for follow-up. Mean follow-up
      was 2 years. Objective success rate regarding the vaginal cuff is 95.4%. Global
      anatomical success rate was 85.5%. Urinary, coital and bowel symptoms were
      improved following surgery. Mesh exposure rate was 19.3%, with all cases managed
      conservatively or with minor interventions. CONCLUSION: Bilateral extraperitoneal
      USL is an effective operation to restore apical support with low morbidity, which
      avoids potential risks associated with opening the peritoneal cavity.

PMID- 19159056
TI  - Image-guided, stereotactic perforator flap surgery: a prospective comparison of
      current techniques and review of the literature.
AB  - BACKGROUND: Image-guided stereotaxy is a recent advancement in imaging
      technology, allowing computer guidance to aid surgical planning and accuracy.
      Despite the use of multiple techniques for patient registration in several
      surgical specialities, only fiducial marker registration has been described for
      use in soft tissue reconstructive surgery. The current study comprises an
      evaluation of the current techniques available for this purpose. METHODS: A
      cohort of nine consecutive patients planned for elective free flaps were
      recruited, with the first five patients (four for the abdominal wall and one
      anterolateral thigh donor site) undergoing fiducial marker registration with a
      variable number of fiducial markers in order to determine the optimal number of
      fiducial markers to be used. Four subsequent patients undergoing perforator flap
      surgery underwent registration using three available registration modalities:
      fiducial marker registration, surface matching pointer/landmark and surface
      matching laser registration. RESULTS: For the abdominal wall, registration was
      not able to be achieved with five fiducial markers, and was successfully achieved
      in all cases with either six or seven fiducial markers. For the anterolateral
      thigh, registration was achieved with either nine or ten markers. The four
      patients who also underwent surface-landmark registration and 'Z-touch' laser
      surface matching registration all failed the registration process. CONCLUSION:
      Stereotactic navigation is a useful adjunct to the preoperative imaging of
      perforator flaps. Fiducial marker registration was able to be achieved in all
      cases, can be successfully achieved with a low and predictable number of fiducial
      markers, is highly accurate, and was the only reliable registration process in
      our experience.

PMID- 19159058
TI  - White matter spectroscopy in neuromyelitis optica: a case control study.
AB  - BACKGROUND: Naa/Cr ratio in normal appearing white matter (NAWM) of patients with
      multiple sclerosis (MS) is altered beyond plaques, suggesting early axonal loss,
      and correlates to clinical disability. Brain lesions not typical of MS have been
      described in Neuromyelitis optica (NMO), and correspond to brain aquaporin-4
      channel sites, but the evaluation of Naa/Cr ratio in NAWM of patients with NMO
      and its association to the presence of brain lesions and clinical disability have
      not been described. OBJECTIVES: To evaluate the Naa/Cr of normal appearing white
      matter (NAWM) in 16 patients with NMO compared to healthy controls. METHODS: We
      performed brain magnetic resonance imaging (MRI) and magnetic resonance
      spectroscopy (MRS) of 16 patients with NMO and compared to age matched healthy
      controls. RESULTS: NAWM Naa/Cr did not show statistical difference among patients
      and controls, neither between patients that had normal brain MRI and atypical
      brain lesions. CONCLUSION: NAWM was found to have a normal Naa/Cr in patients
      with NMO, reinforcing the concept that the white matter is not primarily affected
      in this disease.

PMID- 19159057
TI  - Role of the innate immune system in acute viral myocarditis.
AB  - Although the adaptive immune system is thought to play an important role in the
      pathogenesis of viral myocarditis, the role of the innate immune system has not
      been well defined. To address this deficiency, we employed a unique line of mice
      that harbor a genomic "knock in" of a mutated TNF gene lacking the AU rich
      element (TNF(ARE/ARE)) that is critical for TNF mRNA stability and translation,
      in order to examine the contribution of the innate immune system in
      encephalomyocarditis-induced myocarditis (EMCV). Heterozygous mice (TNF(ARE/+))
      were infected with 500 plaque-forming units of EMCV. TNF(ARE/+)mice had a
      significantly higher 14-day mortality and myocardial inflammation when compared
      to littermate control mice. Virologic studies showed that the viral load at 14
      days was significantly lower in the hearts of TNF(ARE/+) mice. TNF(ARE/+) mice
      had an exaggerated proinflammatory cytokine and chemokine response in the heart
      following EMCV infection. Modulation of the innate immune response in TNF(ARE/+)
      mice by the late administration of prednisolone resulted in a significant
      improvement in survival and decreased cardiac inflammation, whereas early
      administration of prednisolone resulted in a blunted innate response and
      increased mortality in littermate control mice. Viewed together, these data
      suggest that the duration and degree of activation of the innate immune system
      plays a critical role in determining host outcomes in experimental viral
      myocarditis.

PMID- 19159059
TI  - Chronic subthalamic deep brain stimulation improves pain in Parkinson disease.
AB  - BACKGROUND: Pain is a well recognized feature of Parkinson disease (PD). Like
      motor fluctuations, pain in PD may fluctuate as 'non-motor fluctuations'.
      Subthalamic deep brain stimulation (STN DBS) is an established treatment for
      motor fluctuations in PD. However, the effect of STN DBS on the pain in PD is
      only partially investigated. METHODS: PD patients who were considered for STN DBS
      were asked if they had pain. The severity of pain was scored in each body part.
      In patients with motor fluctuation, the pain in the 'on' and 'off ' state were
      recorded separately. Patients were evaluated preoperatively and 3 months after
      surgery. Some patients were followed for 6 months. RESULTS: Twenty-three of 29
      patients had pain preoperatively. Of 24 with motor fluctuation, 21 had pain, and
      18 had fluctuating pain. Pain improved in 20 out of 23 with preoperative pain at
      3 months postoperatively. Of 18 with fluctuating pain, 12 reported a decrease in,
      and 5 complete disappearance of the 'off ' pain. Of 4 with nonfluctuating
      preoperative pain, 2 reported improvement. Pain was severe and functionally
      disabling in some. The STN DBS improved pain to a tolerable degree. In 7 of 29,
      new pain developed during the 3 month follow-up. Sixteen patients were followed
      for 6 months. All 11 patients who had improvement at 3 months continued to get
      benefit from STN DBS. Two additional patients who had no improvement at 3 months
      reported improvement at 6 months. CONCLUSIONS: Pain is frequent in PD and STN DBS
      improves pain, especially the 'off ' pain in PD.

PMID- 19159060
TI  - Internal carotid artery dissection, cerebral aneurysms and thin basement membrane
      nephropathy.

PMID- 19159061
TI  - Ischemic stroke and subarachnoid hemorrhage, two sides of a story: congenital
      absence of the internal carotid artery. Two cases and review of the literature.

PMID- 19159062
TI  - Lower serum ceruloplasmin levels correlate with younger age of onset in
      Parkinson's disease.
AB  - Ceruloplasmin functions as a ferroxidase in iron metabolism. Parkinson's disease
      (PD) is characterized by an increase in brain iron. We postulated that lower
      circulating ceruloplasmin levels in PD would result in rapid brain iron
      accumulation and an earlier age of onset. Consecutive PD patients were separated
      into subgroups with younger (< or = 60 years, n = 62) and older ages of onset (>
      60, n = 29), and compared to non-PD controls (n = 40). A one-way ANOVA comparing
      ceruloplasmin levels showed a very robust effect [F(2,128) = 46.4, p < 1e-99].
      Post hoc analysis demonstrated that the younger-onset PD subgroup [22.0 mg/dl +/-
      6.5 SD] had a lower mean ceruloplasmin level compared to the older-onset PD
      subgroup [35.7 +/- 10.4] and controls [35.6 +/- 8.4], whose levels did not differ
      from each other. Ceruloplasmin levels showed robust correlation with age of onset
      in all 91 PD patients [r = 0.56, r(2) = 0.31, p < 0.0001] but not in the non-PD
      controls [r = 0.16, r(2) = 0.03, not significant]. Mode of onset and duration of
      PD showed no relationship to ceruloplasmin. Serum copper and ferritin, available
      in most patients, did not differ between the PD subgroups. Younger-onset PD
      patients have significantly lower levels of serum ceruloplasmin compared to those
      with older-onset PD. Ceruloplasmin may play a role in the etiopathogenesis of
      younger-onset PD patients and merits further study.

PMID- 19159063
TI  - MRI and clinical syndrome in dura mater-related Creutzfeldt-Jakob disease.
AB  - OBJECTIVE: Iatrogenic Creutzfeldt-Jakob disease (iCJD) is mainly associated with
      dura mater (DM) grafts and administration of human growth hormones (hGH). Data on
      disease course in DM-CJD are limited. We describe the clinical and diagnostic
      findings in this patient group with special emphasis on MRI signal alterations.
      METHODS: Ten DM-CJD patients were studied for their clinical symptoms and
      diagnostic findings. The MRIs were evaluated for signal increase of the cortical
      and subcortical structures. RESULTS: DM-CJD patients had a median incubation time
      of 18 years and median disease duration of 7 months. The majority of patients
      were MM homozygous at codon 129 of the prion protein gene (PRNP) and presented
      with gait ataxia and psychiatric symptoms. No correlation between the graft site
      and the initial disease course was found. The MRI showed cortical and basal
      ganglia signal increase each in eight out of ten patients and thalamic
      hyperintensity in five out of ten cases. Of interest, patients with thalamic
      signal increase were homozygous for methionine. CONCLUSION: The MRI findings in
      DM-CJD largely resemble those seen in sporadic CJD, as the cortex and basal
      ganglia are mainly affected.

PMID- 19159064
TI  - Spinal vascular malformations in non-perimesencephalic subarachnoid hemorrhage.
AB  - OBJECTIVE: In patients with non-traumatic subarachnoid hemorrhage (SAH) and no
      evidence for a cerebral aneurysm on angiography, a frequent cause of the
      hemorrhage is perimesencephalic hemorrhage or other cerebral vascular pathology.
      In some patients no cause is found. The exact incidence of a spinal vascular
      malformation (SVM) as the origin for the SAH is not known. We assessed the
      occurrence of SVM in angiogram-negative, non-perimesencephalic subarachnoid
      hemorrhage (NPSAH). METHODS: 47 patients (from a consecutive cohort of 632) were
      identified with an angiogramnegative, non-perimesencephalic subarachnoid
      hemorrhage and 42 of these were analyzed by performing MR-imaging of the complete
      spinal neuraxis with additional spinal angiography on indication. RESULTS: In
      four patients a spinal vascular malformation was identified as the cause of the
      SAH, indicating an incidence of 9 % of SVM in NPSAH, and an incidence of 1 % of
      SVM in all patients with SAH. INTERPRETATION: Systematic analysis of angiogram
      negative, non-perimesencephalic subarachnoid hemorrhage by MR imaging of the
      complete spinal neuraxis yields a higher incidence of SVM than previously
      documented. We recommend MR imaging of the complete spinal neuraxis in patients
      with a non-perimesencephalic subarachnoid hemorrhage in whom no cause for the
      hemorrhage has been found.

PMID- 19159065
TI  - Acute hemianopic patients do not show a contralesional deviation in the line
      bisection task.

PMID- 19159066
TI  - Steroid-responsive edema in CAA-related inflammation.

PMID- 19159067
TI  - Perfectionism dimensions in pregnancy--a study in Portuguese women.
AB  - Pregnancy is essentially a physiological event, but neuroendocrinal and
      psychosocial changes are also important components of this experience. In this
      context, perceived stress may be enhanced by the activation of certain
      personality traits, like perfectionism, which in turn may be associated with more
      psychological distress (PD). The aim of this study was to investigate if
      perfectionism could be associated with more negative emotional outcomes (PD) in
      the transition to motherhood and to look at which of the perfectionism dimensions
      these consequences are specifically linked. The sample comprises 421 pregnant
      women (mean = 29.8, SD = 4.48 years) who completed measures of perfectionism and
      mood symptoms. A two-factor model with self-oriented perfectionism (SOP) and
      socially prescribed perfectionism (SPP) dimensions and a three-factor model with
      SOP, SPP-others' high standards and SPP-conditional acceptance (CA) factors were
      explored. Correlations and linear regressions were calculated between
      perfectionism factors and mood variables. Results showed that higher levels of
      SPP factors were associated with increased anxiety, depression, anger, fatigue
      and confusion, with decreased vigour and with more severe depressive symptoms.
      Our results, in contrast with those from the study of Campbell and DiPaula (2002,
      In: Flett G, Hewitt P (eds) Perfectionism. Theory, research, and practice.
      American Psychological Association, Washington, pp 181-198), did not confirm a
      preferential association between SPP-CA and PD, revealing that both components of
      SPP were associated with PD.

PMID- 19159068
TI  - Bacterial diversity in the snow over Tibetan Plateau Glaciers.
AB  - Bacterial diversity and cell abundance in the snow of the four glaciers (Guoqu,
      Zadang, East Rongbuk and Palong No. 4) located in different climatic zones of the
      Tibetan Plateau were investigated through culture-independent molecular analysis
      of 16S rRNA gene clone library and flow cytometry approaches. Cell abundance
      ranged from 0.68 x 10(3) to 720 x 10(3) cells mL(-1), with higher values in the
      northern glaciers than in the southern ones. Bacterial diversity was unexpectedly
      high in the snow habitats of the world's highest plateau, with 15 common genera
      distributed widely among the glaciers. The bacterial diversity in the snow at
      different glaciers was related to the surrounding environments. The Guoqu
      Glacier, to the north near the desert zone and with the lowest temperature,
      preserved more bacteria closely related to a cold environment and soil than the
      other glaciers. However, in the Palong No. 4 Glacier located in the south warm
      region around vegetation, most bacteria were phylogenetically related to plant
      associated bacteria.

PMID- 19159069
TI  - Double-balloon endoscopy: past, present, and future.
AB  - Double-balloon endoscopy (DBE) was developed as a new technique for visualization
      of and intervention in the entire small intestine. In DBE, the intestinal walls
      are held apart by a balloon attached to the distal end of a soft overtube. DBE
      has been reported worldwide to be very useful for not only diagnosis but also
      endoscopic therapy. Biopsy samples of small intestinal tumors can be obtained
      using DBE, and the appropriate treatment can be selected before a surgical
      procedure. For inflammatory diseases, DBE can reveal the localization of ulcers
      in the lumen (on the mesenteric or antimesenteric side), which is important for
      differential diagnosis. Some endoscopic therapies such as hemostatic procedures,
      polypectomy, and dilation therapy for benign strictures can be performed in the
      same manner as in the large intestine. DBE may also be suitable for colonoscopy
      for difficult insertion cases and therapeutic procedures such as endoscopic
      submucosal dissection. Furthermore, a double-balloon endoscope can be selectively
      inserted into the afferent loop to perform endoscopic retrograde
      cholangiopancreatography in patients with Roux-en-Y anastomosis, allowing various
      kinds of endoscopic treatments for biliary diseases to be successfully performed.
      Endoscopic therapy in the small intestine, whose wall is very thin, should be
      performed with special care to avoid complications such as bleeding and
      perforation. In the future, improvement is expected in terms of maneuverability,
      therapeutic capability, and imaging technology such as the addition of a
      magnifying function and flexible spectral imaging color enhancement. We
      anticipate that DBE will contribute to the establishment of medical science of
      the small intestine and to research elucidating the mechanisms of small
      intestinal diseases.

PMID- 19159070
TI  - Narrow-band imaging of the gastrointestinal tract.

PMID- 19159072
TI  - Sustained epithelial proliferation in a functionally irreversible fundic mucosa
      after Helicobacter pylori eradication.
AB  - BACKGROUND: We recently reported the expansion of the acid-secreting mucosa
      following Helicobacter pylori eradication with Congo red chromoendoscopy for a
      short-term follow-up of up to 7 months. We aimed to extend the observation period
      and to clarify the characteristic features of acid-secreting and non-acid
      secreting mucosa. METHODS: In 24 H. pylori-positive patients with fundic atrophy,
      Congo red chromoendoscopy was performed prior to, 1 month, 7 months, and finally
      more than 2 years after the eradication. The areas of the acid-secreting mucosa
      were evaluated semiquantitatively. Two gastric biopsy specimens were taken from
      the acid-secreting and non-acid-secreting areas at the final chromoendoscopy and
      were subjected to histologic evaluation and immunohistochemistry for Ki-67 as a
      proliferation index. RESULTS: After a gradual increase in acid-secreting areas
      for up to 7 months after eradication, they further increased in 79% subjects
      between 7 months and the final observation at a mean follow-up of 62 months.
      However, there still existed non-acid-secreting mucosa in the fundic area in all
      subjects, indicating that the expansion of acid-secreting mucosa remained
      partial. Compared with the neighboring acid-secreting area, the non-acid
      secreting area was characterized histologically by higher degrees of residual
      inflammation, mucosal atrophy, and intestinal metaplasia, and by sustained
      hyperproliferation as well. CONCLUSIONS: Functionally irreversible (non-acid
      secreting) gastric mucosa after eradication was associated with extensive
      intestinal metaplasia and sustained hyperproliferation, suggesting that such
      mucosa still possesses malignant potential. Congo red chromoendoscopy may be
      useful for estimating the risk of subsequent development of gastric cancer
      following successful H. pylori eradication by determining the distribution of
      functionally irreversible mucosa.

PMID- 19159071
TI  - Probiotics and immunity.
AB  - Probiotics are defined as live microorganisms that, when administered in adequate
      amounts, confer a health benefit on the host, including the gastrointestinal
      tract. While this beneficial effect was originally thought to stem from
      improvements in the intestinal microbial balance, there is now substantial
      evidence that probiotics can also provide benefits by modulating immune
      functions. In animal models, probiotic supplementation is able to provide
      protection from spontaneous and chemically induced colitis by downregulating
      inflammatory cytokines or inducing regulatory mechanisms in a strain-specific
      manner. In animal models of allergen sensitization and murine models of asthma
      and allergic rhinitis, orally administered probiotics can strain-dependently
      decrease allergen-specific IgE production, in part by modulating systemic
      cytokine production. Certain probiotics have been shown to decrease airway
      hyperresponsiveness and inflammation by inducing regulatory mechanisms. Promising
      results have been obtained with probiotics in the treatment of human inflammatory
      diseases of the intestine and in the prevention and treatment of atopic eczema in
      neonates and infants. However, the findings are too variable to allow firm
      conclusions as to the effectiveness of specific probiotics in these conditions.

PMID- 19159074
TI  - Does Helicobacter pylori-induced inflammation of gastric mucosa determine the
      severity of symptoms in functional dyspepsia?
AB  - BACKGROUND: Inflammation induces some structural and biochemical alterations and
      oxidative damage in gastric tissue. In this study, we aimed to investigate the
      relationship among the severity of symptoms, oxidative stress, and grading scales
      of Helicobacter pylori-induced gastric inflammation in functional dyspepsia.
      METHODS: Thirty-five patients with functional dyspepsia were enrolled in the
      study. The severity of dyspepsia within the last 6 months was evaluated by
      Glasgow Dyspepsia Severity Score. In biopsy specimens of gastric mucosa, severity
      of gastritis was estimated by the revised Sydney Classification System, and
      oxidative stress parameters were studied. RESULTS: Although there was no
      statistically significant relationship between symptom scores and degree of
      chronic inflammation, a tendency for symptoms to be more severe has been observed
      in low levels of gastritis. Levels of sulfhydryl groups were lower in subjects
      with high levels of chronic inflammation, and Helicobacter pylori intensity (P <
      0.001 and P = 0.02, respectively). Levels of malondialdehyde were higher in
      subjects with high levels of chronic inflammation (P = 0.04). There was a
      statistically significant but a weak positive correlation between symptom scores
      and sulfhydryl levels (P < 0.001, r = 0.323). CONCLUSIONS: In conclusion, there
      may be an inverse relation between severity of symptoms and level of Helicobacter
      pylori induced gastric inflammation or oxidative stress in patients with
      functional dyspepsia.

PMID- 19159073
TI  - Extracellular adenosine induces apoptosis in Caco-2 human colonic cancer cells by
      activating caspase-9/-3 via A(2a) adenosine receptors.
AB  - BACKGROUND: Extracellular adenosine has been shown to induce apoptosis in a
      variety of cells via an intrinsic pathway linked to adenosine uptake into cells
      and the ensuing signaling cascades and an extrinsic pathway linked to adenosine
      receptors. The present study was designed to understand the mechanism underlying
      adenosine-induced apoptosis of Caco-2 human colonic cancer cells. METHODS: To
      observe cell viability, an MTT assay was carried out in Caco-2 cells
      untransfected or transfected with the A(2a) adenosine receptor pcDNA3.1.
      Apoptotic cell death was assessed with flow cytometry using propidium iodide and
      annexin V and internucleosomal DNA fragmentation analysis. Activities of caspase
      3, -8, and -9 were measured using a caspase fluorometric assay kit. Mitochondrial
      membrane potentials were monitored using a DePsipher kit. Expression of adenosine
      receptors was examined with the reverse transcription-polymerase chain reaction
      (RT-PCR) method. RESULTS: Extracellular adenosine induced Caco-2 cell apoptosis
      in a concentration-dependent (1-20 mM) and treatment time-dependent (24-72 h)
      manner. The adenosine effect was inhibited by DMPX, an inhibitor of A(2a)
      adenosine receptors and SQ22536, an inhibitor of adenylate cyclase. CGS21680, an
      agonist of A(2a) adenosine receptors, and forskolin, an adenylate cyclase
      activator, mimicked the adenosine action. Caco-2 cell death was still induced by
      overexpressing A(2a) adenosine receptors, and adenosine further promoted the cell
      death. Adenosine disrupted mitochondrial membrane potentials and activated
      caspase-9 and -3, but not caspase-8. CONCLUSIONS: Extracellular adenosine induces
      apoptosis in Caco-2 cells by activating caspase-9 and the downstream effector
      caspase caspase-3 in association with mitochondrial damage via A(2a) adenosine
      receptors.

PMID- 19159075
TI  - Epinephrine sprayed on the papilla for prevention of post-ERCP pancreatitis.
AB  - BACKGROUND: Epinephrine sprayed on the papilla may reduce papillary edema and
      thus prevent acute pancreatitis after endoscopic retrograde
      cholangiopancreatography (ERCP). The aim of this study was to determine the
      efficacy of this technique for prevention of post- ERCP pancreatitis. METHODS:
      Patients scheduled for ERCP were recruited into this study. We randomized the
      patients to have 10 ml of either 0.02% epinephrine (epinephrine group) or saline
      (control group) sprayed on the papilla after diagnostic ERCP and prospectively
      analyzed the occurrence of post-ERCP pancreatitis between the groups. We recorded
      duct visualization, presence of pancreatic acinarization, number of injections
      into the pancreatic duct, total volume of contrast used, and procedure duration.
      RESULTS: There was no significant difference between the groups with regard to
      visualization of the bile duct and/or the main and accessory pancreatic ducts,
      presence of pancreatic acinarization, number of injections into the pancreatic
      duct, total volume of contrast used, and procedure duration. Overall, post-ERCP
      pancreatitis occurred in 4 of the 370 patients (1.1%). The incidence of
      pancreatitis tended to be higher in the control group (4/185) than in the
      epinephrine group (0/185) (P = 0.1230). CONCLUSIONS: Epinephrine sprayed on the
      papilla tended to prevent post-ERCP pancreatitis, although it was not
      statistically significant because of the low incidence of pancreatitis. Further
      studies on the efficacy of this technique in patients at high risk for
      pancreatitis, and on other volumes and/or concentrations of epinephrine, are
      warranted.

PMID- 19159076
TI  - Portosystemic shunts in a large cohort of patients with liver cirrhosis:
      detection rate and clinical relevance.
AB  - BACKGROUND: This study aimed to determine the detection rate and clinical
      relevance of portosystemic collaterals. METHODS: We studied 326 cirrhotics.
      Portosystemic collaterals, portal vein diameter, and splenic area were evaluated
      by color Doppler sonography; esophageal varices were detected by endoscopy.
      RESULTS: Of the cirrhotics, 130 had portosystemic collaterals (39.9% total, left
      gastric vein 11%, paraumbilical vein 7.4%, splenorenal shunts 13.8%, and combined
      shunts 7.7%). Cirrhotics without portosystemic collaterals or with a
      paraumbilical vein had a significantly narrower portal vein diameter than
      cirrhotics with a left gastric vein (P < 0.001). Cirrhotics with a paraumbilical
      vein had a significantly smaller splenic area than cirrhotics with a left gastric
      vein (P < 0.001), splenorenal shunts (P < 0.001), combined shunts (P < 0.001), or
      without portosystemic collaterals (P < 0.05). A significant association between
      portosystemic collaterals and Child's classes or presence and type of esophageal
      varices was found (P < 0.0001 and P = 0.0004, respectively). The highest
      prevalence of Child's class C and large (F-3) esophageal varices was found in
      cirrhotics with a left gastric vein (41.7% and 36.1%, respectively), whereas
      esophageal varices were absent in 47.4% of cirrhotics without portosystemic
      collaterals and in 58.3% of cirrhotics with a paraumbilical vein. CONCLUSIONS:
      The left gastric vein is associated with some sonographic and clinical markers of
      disease severity, whereas the absence of portosystemic collaterals or the
      presence of paraumbilical veins seems to identify cirrhotics with markers
      predictive of a more favorable clinical course.

PMID- 19159077
TI  - Adjuvant radiotherapy for pancreatic cancer is associated with a survival benefit
      primarily in stage IIB patients.
AB  - BACKGROUND: The role of adjuvant radiotherapy (RT) for pancreatic cancer remains
      controversial despite the completion of three multi-institutional randomized
      trials. This study examines the survival impact of postoperative RT in a large
      population-based database. METHODS: Patients with pancreatic cancer diagnosed
      from 1988 to 2003 were identified in the Surveillance, Epidemiology, and End
      Results (SEER) database. The cohort was limited to patients who underwent
      resection of nonmetastatic disease to yield a population of 3252 patients. The
      primary end point was overall survival. Survival analyses were conducted using
      corrections for perioperative mortality as well as a propensity score analysis to
      account for baseline differences in patient characteristics. RESULTS: Multiple
      independent factors were associated with RT use, including patient age and
      disease stage (P < 0.0001). In general, younger patients and those with more
      advanced disease were more likely to receive RT. Disease stage significantly
      affected survival (P < 0.0001). For patients who survived at least 6 months,
      adjuvant RT was associated with increased survival [hazard ratio (HR), 0.87; 95%
      confidence interval (CI), 0.80-0.96]. On subgroup analysis, only stage IIB (T1
      3N1) patients enjoyed a statistically significant benefit associated with RT (HR,
      0.70; 95% CI, 0.62-0.79). CONCLUSIONS: Adjuvant RT is frequently given to
      patients in the United States after resection of their pancreatic cancer.
      Although RT is associated with a survival benefit for nonmetastatic patients as a
      whole, this trend appears to predominantly derive from a survival benefit in
      patients with stage IIB disease.

PMID- 19159078
TI  - miR-21 and 221 upregulation and miR-181b downregulation in human grade II-IV
      astrocytic tumors.
AB  - MicroRNAs (miRNAs) are small noncoding regulatory RNAs that reduce stability
      and/or translation of fully or partially sequence-complementary target mRNAs.
      Recent evidence indicates that miRNAs can function both as tumor suppressors and
      as oncogenes. It has been demonstrated that in glioblastoma multiforme miR-21 and
      221 are upregulated whereas miR-128 and 181 are downregulated. Expression of miR
      21, 221, 128a, 128b, 128c, 181a, 181b, 181c was studied using real-time
      quantitative reverse transcriptase polymerase chain reaction and northern
      blotting for human astrocytic tumors with different grade of malignancy. miR-21
      and 221 were overexpressed in glioma samples, whereas miRNA 181b was
      downregulated compared with normal brain tissue. miRNA-21 was hyperexpressed in
      all tumor samples whereas higher levels of miRNA-221 were found in high-grade
      gliomas. This study is the first analysis of miRNAs in astrocytic tumor at
      different stages of malignancy. The different expression pattern observed in
      tumors at different stages of malignancy is probably dependent on the cell
      specific repertoire of target genes of tumors sharing different molecular
      pathways activity and suggests miRNAs may have also a place in diagnosis and
      staging of brain tumors.

PMID- 19159079
TI  - Can cetuximab affect paraneoplastic myopathy?
AB  - Cetuximab given concurrently with chemotherapy has shown survival benefit for
      patients with metastatic colon cancer. We report a case of a patient with
      metastatic colon cancer who developed paraneoplastic necrotizing myopathy that
      possibly responded to cetuximab despite lack of improvement of the underlying
      cancer.

PMID- 19159080
TI  - Perceptions of economic hardship and emotional health in a pilot sample of family
      caregivers.
AB  - Although several studies have quantified costs of cancer care; none to date have
      examined how cancer costs impact family caregivers' emotional health. This study
      was designed to evaluate how perceptions of economic hardship influence burden,
      depressive symptoms, and anxiety in family caregivers of persons with a primary
      malignant brain tumor. Caregiver (CG)/patient dyads (n = 33) were recruited at
      the time of diagnosis; data were collected at diagnosis and 4 months, and linear
      regression determined the impact of economic hardship on caregivers' emotional
      health. Economic hardship did not predict CG burden-schedule at diagnosis or 4
      months. Economic hardship predicted burden-abandonment at diagnosis (P < 0.01),
      but not 4 months. There was a trend for economic hardship to predict CG
      depressive symptoms at 4 months (P = 0.09), but not at diagnosis. Economic
      hardship predicted CG anxiety at 4 months (P = 0.06), but not diagnosis. Results
      suggest caregivers' economic hardship is an important and dynamic aspect of the
      emotional health of neuro-oncology family caregivers.

PMID- 19159081
TI  - On projection-reconstruction NMR.
AB  - Three most simple Projection-Reconstruction algorithms, namely, the Lowest-Value,
      Additive Back-Projection and Hybrid Back-Projection/Lowest-Value algorithms, are
      analyzed. A new, also simple, algorithm that reconstructs the spectrum by
      utilizing the amplitude histogram at each reconstruction point, is explored. The
      algorithms are tested using simulated spectra. While all the algorithms
      considered can potentially result in substantial reduction of the amount of data
      needed for reconstruction, they can suffer from a number of drawbacks. In
      particular, they often fail when the spectra are noisy and/or contain overlapping
      peaks. When compared to the existing algorithms, the new, histogram-based
      algorithm has the potential advantage of being able to deal with spectra
      containing peaks of opposite phase.

PMID- 19159082
TI  - Fluoride-induced oxidative stress in rat's brain and its amelioration by buffalo
      (Bubalus bubalis) pineal proteins and melatonin.
AB  - Fluoride (F) becomes toxic at higher doses and induces some adverse effects on
      various organs, including brain. The mechanisms underlying the neurotoxicity
      caused by excess fluoride still remain unknown. The aims of this study were to
      examine F-induced oxidative stress (OS) and role of melatonin (MEL) and buffalo
      pineal proteins (PP) against possible F-induced OS in brain of rats. The 24 rats
      were taken in present study and were divided into four groups: control, F, F +
      PP, and F + MEL. The F group was given 150 mg/L orally for 28 days. Combined 150
      ppm F and 100 microg/kg BW (i.p.) PP and F (150 ppm) + MEL (10 mg/kg BW, i.p.)
      were also administered. The activities of enzymatic, viz., superoxide dismutase
      (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR),
      and non-enzymatic, viz., reduced glutathione (GSH) concentration, and the levels
      of malondialdehyde (MDA) in the brain tissue were measured to assess the OS.
      Fluoride administration significantly increased brain MDA compared with control
      group, while GSH levels were decreased in fluoride-treated groups, accompanied by
      the markedly reduced SOD, GPx, GR, and SOD activity. Buffalo PP and MEL
      administration caused brain MDA to decrease but caused SOD, GPx, GR, GSH, and CAT
      activities to increase to significant levels in F-treated animals. Together, our
      data provide direct evidence that buffalo PP and MEL may protect fluoride-induced
      OS in brain of rats through mechanisms involving enhancement of enzymatic and non
      enzymatic antioxidant defense system. Therefore, this study suggested that PP and
      MEL can be useful in control of neurotoxicity induced by fluoride.

PMID- 19159083
TI  - Mass spectrometric and spectroscopic studies of the nutritional supplement
      chromium(III) nicotinate.
AB  - Despite chromium nicotinate's popular use as a chromium nutritional supplement,
      the structure and composition of chromium nicotinate have only been poorly
      described. As solid chromium nicotinate is intractable, being insoluble or
      unstable in common solvents, studies on the solid have been limited, and studies
      of the solution from which the "compound" precipitates have additionally provided
      little additional data. The results of mass spectrometric and spectroscopic
      investigations designed to further elucidate the structure and composition of
      chromium nicotinate are described. The results demonstrated that the three common
      methods for producing "chromium nicotinate" all yield different compounds, all of
      which are polymers of Cr(III), oxygen-bound nicotinate, hydroxide, and water.
      Implications for interpreting results of nutritional studies of "chromium
      nicotinate" are discussed.

PMID- 19159084
TI  - The influence of rich-in-cholesterol diet and fluoride ions contained in potable
      water upon the concentration of malondialdehyde and the activity of selected
      antioxidative enzymes in rabbit liver.
AB  - Two experiments have been carried out, each on 18 (male) rabbits of the New
      Zealand breed. In each of them, animals were divided into three groups of six:
      control group, cholesterol group (CH), and cholesterol + fluoride group (CH+F).
      Experimental hypercholesterolemia has been induced in the animals with the diet
      enriched with 0.5 and 2 g% of cholesterol/100 g of fodder/24 h. The rabbits from
      CH+F groups have also been administered fluoride ions contained in drinking water
      (3 mg F(-)/kg of body mass/24 h). The influence of fluoride ions upon the
      concentrations of malondialdehyde (MDA) and activity of antioxidative enzymes,
      superoxide dismutase (SOD), mitochondrial enzyme (MnSOD), cytoplasmatic enzyme
      (ZnCuSOD), and glutathione peroxidase (GPX), has been examined in liver of
      rabbits. An increase (in comparison with cholesterol groups) in the concentration
      of MDA in both (CH+F) groups in rabbit liver has been noted. Moreover, a decrease
      (statistically significant) of SOD and MnSOD has been found in cholesterol
      groups, as well as in groups (CH+F) in comparison with control group.
      Furthermore, a decrease in the activity of SOD under the influence of F(-)
      together with increased activity of MnSOD (statistically significant in
      comparison with cholesterol groups) have been observed. The activity of ZnCuSOD
      increased in statistically significant manner in (CH) groups vs control group and
      decreased (statistically significantly in relation to cholesterol groups) under
      the influence of F(-).

PMID- 19159087
TI  - A set of piezoelectric biosensors using cholinesterases.
AB  - Piezoelectric sensors have become a versatile tool in biosensorics to study
      protein-protein and protein-small molecule interactions. Here we present
      theoretical background on piezoelectric sensors and instructions, how to modify
      their surface with various recognition elements for cholinesterases. These
      recognition elements comprise an organophosphate (paraoxon), a cocaine derivative
      (BZE-DADOO), and a tricyclic, aromatic compound (propidium). Additionally, a
      guide to the kinetic evaluation of the obtained binding curves is given in this
      chapter.

PMID- 19159085
TI  - Conditional nuclear import and export of yeast proteins using a chemical inducer
      of dimerization.
AB  - In eukaryotes, reversible shuttling between the nucleus and cytoplasm is an
      important regulatory mechanism, particularly for many kinases and transcription
      factors. Inspired by the natural system, we recently developed a technology to
      control protein position in budding yeast using a chemical inducer of
      dimerization (CID). In this method, a nuclear export or localization signal is
      reversibly appended to a protein of interest by the CID, which effectively places
      its subcellular location under direct control of the chemical stimulus. Here, we
      explicitly tested the ability of this system to direct the nucleocytoplasmic
      transport of a panel of 16 representative kinases and transcription factors. From
      this set, we found that 12 targets (75%) are susceptible to re-positioning,
      suggesting that this method might be applicable to a range of targets.
      Interestingly, the four proteins that resisted mislocalization (Fun20p, Hcm1p,
      Pho4p, and Ste12p) are known to engage in a large number of protein-protein
      contacts. We suspect that, for these highly connected targets, the strength of
      the chemical signal may be insufficient to drive mislocalization and that
      proteins with relatively few partners might be most amenable to this approach.
      Collectively, these studies provide a necessary framework for the design of large
      scale applications.

PMID- 19159088
TI  - Piezoelectric biosensors for aptamer-protein interaction.
AB  - Aptamers can be considered as a valid alternative to antibodies or other
      biomimetic receptors for the development of biosensors and other analytical
      methods. The production of aptamers is commonly performed by the SELEX
      (Systematic Evolution of Ligands by Exponential Enrichment) process, which,
      starting from large libraries of oligonucleotides, allows the isolation of large
      amounts of functional nucleic acids by an iterative process of in vitro selection
      and subsequent amplification through polymerase chain reaction. Aptamers are
      suitable for applications based on molecular recognition as analytical,
      diagnostic, and therapeutic tools. The use of aptamers as biorecognition element
      in piezoelectric biosensors will be here reported with particular application to
      the detection of thrombin.

PMID- 19159089
TI  - Piezoelectric quartz crystal resonators applied for immunosensing and affinity
      interaction studies.
AB  - Piezoelectric quartz crystals serve as resonator-based transducers for direct and
      real-time monitoring of immunoaffinity interactions. The measuring system is
      briefly characterized; several examples for immobilization of antibodies are
      recommended. The piezoelectric immunoassays employing direct, competitive, and
      displacement-based formats are demonstrated on examples. The method for kinetic
      characterization of immunoaffinity interactions is presented.

PMID- 19159090
TI  - Biosensors based on cantilevers.
AB  - Microcantilevers based-biosensors are a new label-free technique that allows the
      direct detection of biomolecular interactions in a label-less way and with great
      accuracy by translating the biointeraction into a nanomechanical motion. Low cost
      and reliable standard silicon technologies are widely used for the fabrication of
      cantilevers with well-controlled mechanical properties. Over the last years, the
      number of applications of these sensors has shown a fast growth in diverse
      fields, such as genomic or proteomic, because of the biosensor flexibility, the
      low sample consumption, and the non-pretreated samples required. In this chapter,
      we report a dedicated design and a fabrication process of highly sensitive
      microcantilever silicon sensors. We will describe as well an application of the
      device in the environmental field showing the immunodetection of an organic toxic
      pesticide as an example. The cantilever biofunctionalization process and the
      subsequent pesticide determination are detected in real time by monitoring the
      nanometer-scale bending of the microcantilever due to a differential surface
      stress generated between both surfaces of the device.

PMID- 19159091
TI  - Piezoelectric-excited millimeter-sized cantilever biosensors.
AB  - In this chapter, method of fabricating a cantilever biosensors and their use in
      measuring the presence of a protein is described. There are many variations in
      construction of a cantilever sensor. A simple and an easy version is described in
      this chapter. The specificity of the sensor is obtained by immobilizing an
      antibody specific to the antigen of interest. The piezoelectric cantilever
      sensors are very sensitive and can easily detect a 60 kDa protein at 100 fg/mL
      concentration. Experimental procedure for carrying out detection of a target
      analyte is outlined and a sample set of results is included.

PMID- 19159092
TI  - Preparation of screen-printed electrochemical immunosensors for estradiol, and
      their application in biological fluids.
AB  - The method of fabrication of a prototype electrochemical immunosensor for
      estradiol (E2) is described. Methodologies are also given for colorimetric
      assays, which can be used to verify and optimize reagent performance, prior to
      their use in the electrochemical immunoassay: these include an E2 ELISA and a
      colorimetric assay performed on the immunosensor surface. The electrochemical
      immunosensor system uses screen-printed carbon electrodes (SPCEs) upon which
      antibody against E2 is immobilized. Antibodies (rabbit anti-mouse IgG, then
      monoclonal mouse anti-E2) are immobilized by passive adsorption onto the working
      electrode surface. A competitive immunoassay is then performed using an alkaline
      phosphatase-labeled E2 conjugate. Electrochemical measurements are performed
      using differential pulse voltammetry (DPV) to detect the production of 1-naphthol
      from 1-naphthyl phosphate. The calibration plot of DPV peak current vs. E2
      concentration shows a measurable range of 25-500 pg/mL with a detection limit of
      50 pg/mL. The immunosensor can be applied to the determination of E2 in spiked
      serum, following an extraction step with diethyl ether.

PMID- 19159093
TI  - Electrochemical DNA biosensors: protocols for intercalator-based detection of
      hybridization in solution and at the surface.
AB  - An electrochemical DNA biosensor is a device that utilizes the inherent ability
      of two complementary strands of nucleic acids to form a double helix. The
      specificity of this reaction, namely hybridization, is used in the detection of
      target DNA sequences with a view toward developing point-of-care devices. Since
      the early 1990s, great progress has been made in this field, but there are still
      numerous challenges to overcome. This chapter describes the components of an
      electrochemical DNA biosensor for researchers new to the field, paying particular
      attention to intercalator-based DNA biosensors. We will use a well-defined
      electro-active DNA intercalator Hoechst 33258, as our running example. Two of the
      most classic DNA sensing methods: solution-based and surface-immobilized methods
      are discussed, along with guiding notes that would help identify and overcome
      possible problems in a typical electrochemical DNA biosensor experiment.

PMID- 19159094
TI  - Electrochemical biosensor technology: application to pesticide detection.
AB  - In recent years, electrochemical sensors and biosensors are becoming an accepted
      part of analytical chemistry since they satisfy the expanding need for rapid and
      reliable measurements. An area in which electrochemical biosensors perhaps show
      the greatest diversity and potential for development involves the measurement of
      environmentally significant parameters. The increasing number of pollutants in
      the environment calls for fast and cost-effective analytical requirements. In
      this context, biosensors appear as suitable alternative or complementary
      analytical tools. The aim of this chapter is to review some basic concept
      concerning the electrochemical biosensors and to illustrate a protocol for the
      detection of environmental organic pollutants on the basis of electrochemical
      biosensors. In particular, a method based on the inhibition of the enzyme
      acetylcholinesterase (AChE) for the detection of organophosphorus and carbamate
      pesticides will be described in detail.

PMID- 19159095
TI  - Electrochemical detection of DNA hybridization using micro and nanoparticles.
AB  - A novel, rapid, and sensitive protocol for the electrochemical detection of DNA
      hybridization that take the advantage of a magnetic separation/mixing process and
      the use of monomaleimido-gold nanoparticles of 1.4 nm diameter as label is
      presented. A sandwich-type assay is formed in this protocol by the capture probe
      DNA immobilized on the surface of magnetic beads and the double hybridization of
      the target (cystic fibrosis related DNA), first with the immobilized probe, and
      then with signaling probe DNA labeled with monomaleimido-gold nanoparticles. When
      the assay is completed, the final conjugate is transferred onto genomagnetic
      sensor surface (graphite epoxy composite electrode with a magnet inside) used as
      working electrode, and then the direct determination of gold nanoparticles by
      differential pulse voltammetry striping technique is carried out. This protocol
      is quite promising for numerous applications in different fields as clinical
      analysis, environmental control as well as other applications.

PMID- 19159096
TI  - Electrochemical immunosensing using micro and nanoparticles.
AB  - A model immunosensor based on a labeling method using gold nanoparticles (AuNPs)
      and electrochemical detection is developed. Microparamagnetic beads (MB) as
      primary antibody immobilization platforms and AuNPs modified with a secondary
      antibody as high sensible electrochemical labels have been used. The carbon
      electrode used as transducer incorporates a magnet that allows the collection/
      immobilization on its surface of the immunological sandwich attached to the MB.
      Briefly, the sandwich type assay consists in the incubation of streptavidin
      coupled-MB with an antihuman IgG biotin conjugate, and then, the immunological
      reaction with the human IgG antigen takes place. After that, a gold labeled anti
      human IgG reacts with the antigen, and finally the AuNPs are electrochemically
      detected. This approach allows the obtaining of an immunosensor with a low
      antigen detection limit with special interest for several applications in protein
      analysis.

PMID- 19159097
TI  - Methods for the preparation of electrochemical composite biosensors based on gold
      nanoparticles.
AB  - Methods for the construction of electrochemical composite biosensors using gold
      nanoparticles and Teflon as nonconducting-binding material are described in
      detail. The advantages of the incorporation of gold nanoparticles to the
      composite electrode matrices are highlighted, giving rise to bioelectrodes with
      improved analytical performance in terms of stability and sensitivity with
      respect to other biosensor designs. Three different biosensors have been
      considered: a tyrosinase biosensor in which the enzyme and gold nanoparticles are
      incorporated into graphite-Teflon composite electrode matrices by simple physical
      inclusion, a progesterone immunosensor in which the antibody is directly attached
      to the electrode surface and amperometric transduction is carried out at a
      colloidal gold-graphite-Teflon-tyrosinase composite biosensor, and a mediator
      less glucose oxidase biosensor constructed by bulk incorporation of the enzyme
      into colloidal gold-multiwall carbon nanotubes-Teflon composite electrodes.

PMID- 19159098
TI  - Immunochromatographic lateral flow strip tests.
AB  - The immunochromatographic lateral flow strip test is a one-step test that
      facilitates low-cost, rapid identification of various analytes at the point of
      care. We have developed lateral flow strip tests for the specific qualitative or
      semiquantitative detection of antigens, antibodies, and haptens, such as drug
      residues. Here, we describe in detail the preparation of three examples of the
      strip tests for detection of (a) the infectious bursal disease virus; (b)
      Trichinella specific antibodies, and (c) Clenbuterol residues in urine samples.

PMID- 19159099
TI  - Liposome-enhanced lateral-flow assays for the sandwich-hybridization detection of
      RNA.
AB  - Clinical and environmental analyses frequently necessitate rapid, simple, and
      inexpensive point-of-care or field tests. These semiquantitative tests may be
      later followed up by confirmatory laboratory-based assays, but can provide an
      initial scenario assessment important for resource mobilization and threat
      confinement. Lateral-flow assays (LFAs) and dip-stick assays, which are typically
      antibody-based and yield a visually detectable signal, provide an assay format
      suiting these applications extremely well. Signal generation is commonly obtained
      through the use of colloidal gold or latex beads, which yield a colored band
      either directly proportional or inversely proportional to the concentration of
      the analyte of interest. Here, dye-encapsulating liposomes as an alternative are
      discussed. The LFA biosensors described in this chapter rely on the sandwich
      hybridization of a nucleic acid sequence-based amplified (NASBA) mRNA target
      between a membrane immobilized capture probe and a visible dye (sulforhodamine B)
      encapsulating liposome conjugated reporter probe. Although the methodology of
      this chapter is focused on LFAs for the detection of RNA through sandwich
      hybridization, the information within can be readily adapted for sandwich and
      competitive immunoassays. Included are an introduction and application notes
      toward this end. These include notes ranging from the detection of nonamplified
      RNA and single-stranded DNA, conjugation protocols for antibodies and other
      proteins to liposomes, and universal assay formats.

PMID- 19159100
TI  - Rapid prototyping of lateral flow assays.
AB  - Principles and characteristics of lateral flow strip assays are reviewed. Recent
      technology developments permit the use of inexpensive electronic readers for
      interrogating lateral flow strip test results, thus avoiding the inevitable
      variation and subjectivity of visual inspection to assess the capture of reporter
      labeled analyte on test lines of the strip. Protocols for developing lateral flow
      assays are described, including two specific case studies for assaying cotinine
      (a small-molecule metabolite of nicotine) in a competitive format, and assaying
      HIV antibodies in a sandwich-type assay format.

PMID- 19159101
TI  - Lateral flow colloidal gold-based immunoassay for pesticide.
AB  - In recent years, immunochromatographic lateral flow test strips are used as a
      popular diagnostic tool. There are two formats (noncompetitive and competitive)
      in gold-based immunoassay. Noncompetitive gold-based immunoassay also called
      sandwich assay is applied for the detection of large molecular mass. For small
      molecular mass such as pesticide, competitive format of lateral flow colloidal
      gold-based immunoassay is described in this chapter. The preparation of gold
      colloidal and the conjugation between antibody and gold colloidal are described.
      Hi-flow plus nitrocellulose membranes are separately coated with goat anti-rabbit
      IgG (control line) and hapten-OVA conjugate (test line). Thus, the degree of
      intensity of color of the test line is the reverse of the concentration of
      pesticide in the sample and the visual result is immediately observable.
      Colloidal gold-based immunoassay can also be applied for multianalysis in one
      test strip if the detected targets show different physico-chemical properties and
      their haptens show great differences in chemical structure.

PMID- 19159102
TI  - Synthesis of a virus electrode for measurement of prostate specific membrane
      antigen.
AB  - Though relatively unexploited in biosensor applications, phage display technology
      can provide versatile recognition scaffolds for detection of cancer markers and
      other analytes. This chapter details protocols for covalent attachment of viruses
      directly to electrodes for reagent-free detection of analytes in real-time.
      Customization of binding specificity leverages selections with large phage
      display libraries prior to covalent attachment of the selected virus to the
      electrode. The methods described here utilize electrochemical impedance
      spectroscopy (EIS) to detect molecular recognition between M13 phage bound to a
      Au electrode and the following analytes: prostate specific membrane antigen
      (PSMA), positive and negative control antibodies (p-Ab and n-Ab, respectively).
      Because of a thick layer built on the Au electrode, the real impedance (Zre)
      increases reliably with S/N ratios upon noncovalent binding to PSMA
      (approximately 14) and p-Ab (approximately 20).

PMID- 19159103
TI  - In vivo bacteriophage display for the discovery of novel peptide-based tumor
      targeting agents.
AB  - A powerful strategy for targeted drug discovery is the use of bacteriophage
      (phage) display technology for identification of peptide-based tumor targeting
      agents. Peptide pharmaceuticals may possess clinically desirable properties
      because of their rapid blood clearance, non-immunogenic nature, and ease of
      synthesis. Phage display has identified hundreds of different peptide sequences
      that bind a desired target in vitro. Regrettably, few of these peptides offer
      good targeting efficacy in vivo. One reason for this is the synthesized peptide
      may not retain its optimal activity outside the microenvironment of the phage.
      Another possible explanation is that traditionally, phage selections are
      performed in vitro outside the complicated milieu of a living animal. Given these
      shortcomings, we have developed methods to select phage peptide display libraries
      in living mice, to identify, a priori, phage (and corresponding synthesized
      peptides) with ideal tumor-targeting propensity.

PMID- 19159104
TI  - Biopanning of phage displayed peptide libraries for the isolation of cell
      specific ligands.
AB  - One limitation in the development of biosensors for the early detection of
      disease is the availability of high specificity and affinity ligands for
      biomarkers that are indicative of a pathogenic process. Within the past 10 years,
      biopanning of phage displayed peptide libraries on intact cells has proven to be
      a successful route to the identification of cell-specific ligands. The peptides
      selected from these combinatorial libraries are often able to distinguish between
      diseased cells and their normal counterparts as well as cells in different
      activation states. These ligands are small and chemical methodologies are
      available for regiospecific derivatization. As such, they can be incorporated
      into a variety of different diagnostic and therapeutic platforms. Here we
      describe the methods utilized in the selection of peptides from phage displayed
      libraries by biopanning. In addition, we provide methods for the synthesis of the
      selected peptides as both monomers and tetramers. Downstream uses for the
      peptides are illustrated.

PMID- 19159106
TI  - Antibody affinity optimization using yeast cell surface display.
AB  - Many biosensors depend on molecular recognition reagents to achieve highly
      sensitive and specific detection levels of an analyte of interest. Although new
      and improved detection platforms continue to be developed, improvements in the
      affinity and specificity of the molecular recognition reagents often dictate the
      ultimate performance level and utility of the instrument. Accordingly, large
      effort is placed in discovering and characterizing the reagents to be used for a
      biosensor application. Antibodies, owing to their unparalleled ability to bind a
      diverse array of antigens with high affinity and specificity, have been widely
      used as molecular recognition reagents in the biosensor field. The recent advent
      of recombinant in vitro antibody display technologies, in general, and yeast
      surface display, in particular, allow specific traits of a given antibody to be
      discreetly augmented to enhance biosensor performance. Large variegated libraries
      derived from existing antibodies already employed in a particular biosensor can
      be created and screened for mutations that confer a desired improved phenotype
      leading to enhanced biosensor performance. This chapter will provide a protocol
      for the affinity maturation of a previously isolated monoclonal antibody, the
      most widely used application of in vitro directed evolution.

PMID- 19159105
TI  - Biosensor detection systems: engineering stable, high-affinity bioreceptors by
      yeast surface display.
AB  - Over the past two decades, the field of biosensors has been developing fast,
      portable, and convenient detection tools for various molecules of interest, both
      biological and environmental. Although much attention is paid to the transduction
      portion of the sensor, the actual bioreceptor that binds the ligand is equally
      critical. Tight, specific binding by the bioreceptor is required to detect low
      levels of the relevant ligand, and the bioreceptor must be stable enough to
      survive immobilization, storage, and in ideal cases, regeneration on the
      biosensing device. Often, naturally-occurring bioreceptors or antibodies that are
      specific for a ligand either express affinities that may be too low to detect
      useful levels, or the proteins are too unstable to be used and reused as a
      biosensor. Further engineering of these receptors can improve their utility.
      Here, we describe in detail the use of yeast surface display techniques to carry
      out directed evolution of bioreceptors to increase both the stability of the
      molecules and their affinity for the ligands. This powerful technique has enabled
      the production of stabilized, single-chain antibodies, T cell receptors, and
      other binding molecules that exhibit affinity increases for their ligands of up
      to 1 million-fold and expression of stable molecules in E. coli.

PMID- 19159107
TI  - Using RNA aptamers and the proximity ligation assay for the detection of cell
      surface antigens.
AB  - The detection and typing of tumor cells based on differentially or similarly
      expressed antigens (biomarkers) have proven to be increasingly important for the
      diagnosis and treatment of various cancers. Sensitive techniques for the
      detection of cell surface antigens are therefore crucial for the early and
      accurate detection of cancer. Although techniques such as ELISA and tissue
      staining have proven their worth, these techniques often either require
      substantial amounts of starting material or are prone to high background and
      false negatives. The proximity ligation assay (PLA) has proven to be an
      exquisitely sensitive technique with very low background. Two probes that bind
      adjacent to one another on a protein target can be ligated, yielding a unique
      amplicon that can be sensitively detected by real-time PCR. We have now adapted
      PLA to cell surface protein targets using modified RNA aptamers, and have shown
      that aptamer-based cell surface PLA can successfully detect and differentiate
      between cells that differentially express a tumor antigen, the prostate specific
      membrane antigen (PSMA).

PMID- 19159108
TI  - In vitro selection of protein-binding DNA aptamers as ligands for biosensing
      applications.
AB  - Aptamers are single-stranded functional nucleic acids that possess cognate ligand
      recognition capability. These functional nucleic acids have been used for
      biosensing of a variety of ligands. Aptamers are isolated by "in vitro selection"
      or SELEX from random-sequence nucleic acid pools. For example, DNA aptamers that
      recognize a protein can be generated by applying a DNA library to an affinity
      column containing the protein target and retrieving the bound sequences after
      wash. These sequences are amplified and used for a new round of binding and
      amplification. The identity of enriched sequences are subsequently revealed by
      cloning and sequencing. The binding of individual aptamers to the protein can be
      confirmed by techniques such as gel mobility shift. This chapter will provide a
      detailed protocol for isolating protein-binding DNA aptamers.

PMID- 19159109
TI  - Immobilization of biomolecules onto silica and silica-based surfaces for use in
      planar array biosensors.
AB  - Several methods are described in which a biological recognition molecule--a
      critical element in any biosensor--is immobilized onto a silica or silica-based
      sensing substrate. Although several variations are described, the methods for
      covalent immobilization share a common theme and are generally composed of three
      steps: modification of the surface to add specific functional groups (using
      appropriate silanes or an amine or carboxyl-containing hydrogel), covalent
      attachment of a crosslinker through one of its reactive moieties, and finally,
      covalent linking of the biomolecule (recognition element) to the remaining
      reactive moiety of the crosslinker. One final method is presented in which the
      surface is modified with a highly hydrophobic silane and a glycolipid recognition
      element immobilized, essentially irreversibly, by hydrophobic interactions. All
      of the methods described have been successfully used to immobilize biological
      recognition molecules onto sensing surfaces, with full functionality in biosensor
      binding assays.

PMID- 19159110
TI  - Rapid DNA amplification using a battery-powered thin-film resistive thermocycler.
AB  - A prototype handheld, compact, rapid thermocycler was developed for multiplex
      analysis of nucleic acids in an inexpensive, portable configuration. Instead of
      the commonly used Peltier heating/cooling element, electric thin-film resistive
      heater and a miniature fan enable rapid heating and cooling of glass capillaries
      leading to a simple, low-cost Thin-Film Resistive Thermocycler (TFRT). Computer
      based pulse width modulation control yields heating rates of 6-7 K/s and cooling
      rates of 5 K/s. The four capillaries are closely coupled to the heater, resulting
      in low power consumption. The energy required by a nominal PCR cycle (20 s at
      each temperature) was found to be 57+/-2 J yielding an average power of
      approximately 1.0 W (not including the computer and the control system). Thus the
      device can be powered by a standard 9 V alkaline battery (or other 9 V power
      supply). The prototype TFRT was demonstrated (in a benchtop configuration) for
      detection of three important food pathogens (E. coli ETEC, Shigella dysenteriae,
      and Salmonella enterica). PCR amplicons were analyzed by gel electrophoresis. The
      35 cycle PCR protocol using a single channel was completed in less then 18 min.
      Simple and efficient heating/cooling, low cost, rapid amplification, and low
      power consumption make the device suitable for portable DNA amplification
      applications including clinical point of care diagnostics and field use.

PMID- 19159112
TI  - Tibial torsion in cerebral palsy: validity and reliability of measurement.
AB  - Physical examinations of tibial torsion are used for preoperative planning and to
      assess outcomes of tibial osteomy in patients with cerebral palsy (CP). The thigh
      foot angle (TFA) and transmalleolar axis (TMA) are commonly used, and the second
      toe test recently was introduced. However, the validity and reliability of the
      three methods have not been clarified. This study was performed to evaluate the
      validity and reliability of these physical measures. We recruited 18 patients (36
      limbs) with CP. During reliability sessions, three raters with various levels of
      orthopaedic experience independently measured tibial torsion using the three
      different methods during one day before surgery. Validity was assessed by
      performing a correlation study between physical examination and two-dimensional
      computed tomographic (CT) findings. Interobserver reliability was greatest for
      the TMA followed by TFA and then by the second toe test with intraclass
      correlation coefficients of 0.92, 0.74, and 0.57, respectively. In terms of the
      concurrent validity, the correlation coefficients (r) for the CT measurements
      were 0.62, 0.52, and 0.55. When depicting tibial torsion by physical examination,
      all three methods had substantial validity, but test reliability and validity
      were highest for TMA measurements. LEVEL OF EVIDENCE: Level I, diagnostic study.
      See the Guidelines for Authors for a complete description of levels of evidence.

PMID- 19159113
TI  - Letter to the editor: Recognizing and preventing burnout among orthopaedic
      leaders.

PMID- 19159114
TI  - Gait analysis after initial nonoperative treatment for clubfeet: intermediate
      term followup at age 5.
AB  - We conducted gait analysis following initial nonoperative clubfoot treatment to
      compare lower extremity kinematic (eg, ankle motion) and kinetic (eg, ankle
      power) characteristics between patients treated as infants with Ponseti casting
      or French physical therapy. This is a followup report of gait characteristics at
      age 5 years in patients who had previously been tested at age 2 years. One
      hundred-twenty five clubfeet in 90 patients (34 feet only Ponseti treatment, 40
      only French PT, and 51 feet initial nonoperative treatment followed by surgery)
      were included. The gait characteristics were compared to those of age-matched
      normal control subjects. Ankle equinus during gait occurred in 5% of feet treated
      with the French method and none of those treated by the Ponseti method. Increased
      stance phase ankle dorsiflexion persisted in 24% of feet treated by the Ponseti
      method. Intoeing was seen in 1/3 of both the French and Ponseti methods. Ankle
      push-off power was decreased compared to normal in patients treated by both
      methods, and even more so in operated feet. The presence or absence of Achilles
      tenotomy did not affect ankle power. Gait characteristics of feet that did not
      have surgery and maintained correction were superior to those of operated feet.

PMID- 19159115
TI  - Evaluation of CAND2 and WNT7a as candidate genes for congenital idiopathic
      clubfoot.
AB  - Congenital idiopathic clubfoot is a common pediatric musculoskeletal deformity
      with no known etiology. The deformity reportedly follows a Mendelian pattern of
      inheritance. Recent work has demonstrated linkage in chromosome 3 and 13 in a
      large, multigeneration, highly penetrant family with idiopathic clubfoot. From
      the linkage region on chromosome 3, we selected the candidate genes CAND2 and
      WNT7a, which are involved in lower extremity development, and hypothesized
      mutations in these genes would be associated with the phenotype of congenital
      idiopathic clubfoot. The CAND2 gene was sequenced in 256 clubfoot patients, and
      75 control patients, while WNT7a was screened using 56 clubfoot patients and 50
      control patients. We found a polymorphism in each gene, but the single nucleotide
      change in CAND2 was a silent mutation that did not alter the amino acid product,
      and the single nucleotide change in WNT7a was in the upstream, non-coding or
      promoter region before the start codon. Based on these results it is unlikely
      CAND2 and WNT7a are the major genes that causes clubfoot, however WNT7a might be
      one of many genes that could increase susceptibility to develop clubfoot but do
      not directly cause it.

PMID- 19159116
TI  - Evaluation of a disease-specific instrument for idiopathic clubfoot outcome.
AB  - In 2001, Roye et al. developed a disease-specific instrument (DSI) to measure
      outcomes of treatment for clubfoot. We assessed this instrument using a cohort of
      62 patients, ages 5 through 12 years (mean, 8.6 years), with idiopathic clubfoot
      who were treated as infants by various methods. Treatment groups were defined by
      whether the patient received joint-invasive surgery (posterior or posteromedial
      release surgery) or joint-sparing treatment only (manipulation and casting with
      or without tendo-Achilles lengthening or anterior tibial tendon transfer). The
      DSI scales demonstrated internal consistency reliability of 0.74 to 0.85 using
      Cronbach's alpha. Higher (better) DSI scores were associated with "excellent"
      general health ratings and better health-related quality of life; lower DSI score
      were related to special healthcare needs. Patients treated using joint-sparing
      techniques only (eg, Ponseti technique) had higher DSI scores than those who had
      received joint-invasive surgery. DSI scores for patients who had received
      posterior or posterior medial release surgery were very similar to those reported
      by Roye et al. in New York for a comparable group of patients. Our findings
      suggest the DSI is sensitive to differences in treatment technique or underlying
      severity of disease. These data support the use of the Roye DSI as an outcome
      measure for idiopathic clubfoot in children. LEVEL OF EVIDENCE: Level III,
      diagnostic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 19159117
TI  - Treatment of canine osseous tumors with photodynamic therapy: a pilot study.
AB  - Photodynamic therapy uses nonthermal coherent light delivered via fiber optic
      cable to locally activate a photosensitive chemotherapeutic agent that ablates
      tumor tissue. Owing to the limitations of light penetration, it is unknown
      whether photodynamic therapy can treat large osseous tumors. We determined
      whether photodynamic therapy can induce necrosis in large osseous tumors, and if
      so, to quantify the volume of treated tissue. In a pilot study we treated seven
      dogs with spontaneous osteosarcomas of the distal radius. Tumors were imaged with
      MRI before and 48 hours after treatment, and the volumes of hypointense regions
      were compared. The treated limbs were amputated immediately after imaging at 48
      hours and sectioned corresponding to the MR axial images. We identified tumor
      necrosis histologically; the regions of necrosis corresponded anatomically to
      hypointense tissue on MRI. The mean volume of necrotic tissue seen on MRI after
      photodynamic therapy was 21,305 mm(3) compared with a pretreatment volume of 6108
      mm(3). These pilot data suggest photodynamic therapy penetrates relatively large
      canine osseous tumors and may be a useful adjunct for treatment of bone tumors.

PMID- 19159118
TI  - On the origins of complex immune-mediated disease: the example of rheumatoid
      arthritis.
AB  - This essay discusses strategies for understanding the origins and outcomes of
      complex chronic inflammatory diseases using genetic and environmental
      determinants as tools for new definitions of disease subsets. Rheumatoid
      arthritis has been chosen as the prototype to illustrate these general concepts.
      Through recent data on two different disease subsets, it has been possible to
      devise a new molecular model for disease development by incorporating multiple
      genes and environmental agents which generate immune reactions that may
      eventually cause disease. These kinds of studies, aiming to integrate genetic
      epidemiology and molecular immunology, require close proximity between
      institutions for molecular medicine, clinical departments able to provide follow
      up, careful surveillance of large patient groups and collaboration with experts
      in epidemiology and biostatistics.

PMID- 19159119
TI  - [Do we really not need a "trauma leader" in the emergency room?].

PMID- 19159120
TI  - [Polytrauma management in a period of change: time analysis of new strategies for
      emergency room treatment].
AB  - BACKGROUND: Quality management and the early implementation of whole-body multi
      slice spiral computed tomography (whole-body MSCT) are becoming increasingly
      important in the management of patients with multiple trauma. The aim of this
      study was to evaluate both components with respect to the time factor for
      treatment. METHODS: The investigation involved a retrospective data analysis of
      the time needed in the emergency room for the initial stabilization (phase A),
      completing the diagnosis (phase B) and the emergency room treatment (phase C).
      The investigation included three groups: trauma patients imaged in the emergency
      room with conventional imaging procedures (group I), with whole-body MSCT alone
      (group II) and those who were imaged with whole-body MSCT after the introduction
      of a quality management system with standard operating procedures (group III).
      RESULTS: The times for resuscitation (phase A), for diagnostic evaluation (phase
      B) and for total treatment (phase C) were analyzed. The times for phase A were
      for group I (n=79) 10 min (interquartile range, IQR 8-12 min), group II (n=82) 13
      min (IQR 10-17 min) and group III (n=79) 10 min (IQR 8-15 min; p<0.001). The
      times for phase B were 70 min (IQR 56-85 min) for group I, 23 min (IQR 17-33 min)
      for group II and 17 min (IQR 13-21 min; p<0.001) for group III. For phase C the
      times were 82 min (IQR 66-110 min) for group I, 47 min (IQR 37-59 min) for group
      II and 42 min (IQR 34-52 min; p<0.05) for group III. CONCLUSION: Quality
      management and the early implementation of whole-body MSCT can accelerate the
      treatment work flow. A rapid initial diagnosis represents an important component
      in the high quality of treatment of polytrauma patients.

PMID- 19159122
TI  - Peripheral arterial disease in the elderly: recognition and management.
AB  - Peripheral arterial disease (PAD) is a common but frequently overlooked vascular
      disease, often affecting the lower extremities. The prevalence of PAD increases
      exponentially with age, and this is of particular concern among the elderly
      population because this condition frequently signals disease in other vascular
      beds, including the coronary arteries and/or cerebral vasculature. In addition to
      the increased risk of cardiovascular disease and stroke, patients with PAD may
      also experience functional impairment and decreased quality of life. The ankle
      brachial index is the most effective and widely used screening tool for detecting
      PAD and should be performed when PAD is suspected, based on the medical history
      or physical examination. Current treatment guidelines recommend risk factor
      modification, including exercise therapy and smoking cessation interventions,
      combined with pharmacologic measures for secondary prevention and management of
      symptoms of PAD. Antiplatelet therapy is an integral component of global
      cardiovascular risk reduction strategies in patients with PAD.Current guidelines
      provide a significant opportunity for practitioners to detect and treat patients
      with PAD in a timely and effective manner, thereby improving the overall
      mortality, morbidity, and quality of life associated with this disease.

PMID- 19159123
TI  - Candidate mechanisms for regression of coronary atherosclerosis with high-dose
      statins: insight from intravascular ultrasonography trials.
AB  - Animal models and serial imaging studies in humans have shown that
      atherosclerosis is a potentially reversible disease. Several drug classes have
      been tested to determine whether they can promote reversal of atherosclerosis. Of
      these, HMG-CoA reductase inhibitors (statins) have been consistently proven to
      have anti-atherosclerotic effects in large-scale clinical trials. In this
      article, we review the lipid- and non-lipid-based mechanisms of statin-induced
      disease regression using the information provided by the recent intravascular
      ultrasonography trials. We conclude that, despite several potential mechanisms,
      reduction of low-density lipoprotein cholesterol appears to be the dominant
      mechanism responsible for regression of atherosclerosis.

PMID- 19159125
TI  - Cost effectiveness of ezetimibe in patients with cardiovascular disease and
      statin intolerance or contraindications: a Markov model.
AB  - OBJECTIVE: To evaluate the cost effectiveness of long-term ezetimibe monotherapy
      in patients with established cardiovascular disease (CVD) who do not tolerate
      statins or in whom they are contraindicated. METHODS: A Markov model was used to
      estimate the potential costs and benefits associated with ezetimibe monotherapy
      compared with no treatment. The benefits associated with ezetimibe treatment were
      informed by a systematic review of clinical evidence and a published relationship
      linking changes in low-density lipoprotein cholesterol (LDL-C) levels to
      cardiovascular events. RESULTS: In the absence of data from clinical outcome
      trials, surrogate endpoints such as changes in lipid levels were used as
      indicators of clinical outcomes. A meta-analysis of seven placebo-controlled
      trials included in the review showed that ezetimibe was associated with a
      statistically significant mean reduction (from baseline to endpoint) in LDL-C of
      18.56% (95% CI -19.68, -17.44; p < 0.00001) compared with placebo. Using 10,000
      Monte Carlo simulations, it is estimated that ezetimibe monotherapy would prevent
      an average of 49 nonfatal myocardial infarctions, 11 nonfatal strokes, and 37
      cardiovascular deaths in a cohort of 1,000 patients aged 55 years with a baseline
      LDL-C concentration of 4.0 mmol/L. Events avoided provide an additional 211
      quality-adjusted life-years (QALYs) over the 45 years modeled. With a mean
      incremental cost of pound 4,861,000 (year 2006 value), the discounted cost per
      QALY is pound 23,026 (Jackknife CI 22 979, 23 074). The model is reasonably
      robust to variations in key parameters. Incremental cost-effectiveness ratios
      fall below pound 20,000 per QALY for cohorts with baseline LDL-C values >4.5
      mmol/L. CONCLUSION: Ezetimibe monotherapy compared with no treatment is a cost
      effective alternative for individuals with a history of CVD and high LDL-C
      levels, who do not tolerate statins or in whom they are contraindicated.

PMID- 19159126
TI  - Identifying the nonpoint source of perfluorinated compounds using a geographic
      information system based approach.
AB  - Perfluorinated compounds (PFCs) have been detected in a wide range of places.
      They have also been reported to come from nonpoint sources, but the origin of
      these sources has not been identified. In the present study, we attempted to
      characterize the nonpoint source of PFCs in the Hayabuchi River, Japan, which
      runs through an urban area, using a geographic information system (GIS) and
      statistical analysis. We also estimated annual PFC loads from nonpoint sources in
      Japan as a whole, determining a magnitude comparable to that from sewage
      treatment plants (STPs); the range was a few tons per year for each PFC.
      Perfluorinated compound pollution in river water was found to increase when the
      river received drainage from an area with a high proportion of commercial and/or
      transportation land use. It was also found that more PFCs were discharged from
      the watersheds where train stations are located. This result could be interpreted
      as the use of land for commercial and transportation purposes is prevalent in
      close proximity to train stations, and that the effluents from those areas
      contain high concentrations of PFCs. These findings suggested that train stations
      could be indicators of nonpoint sources of PFCs.

PMID- 19159127
TI  - Assessing the importance of dietborne cadmium and particle characteristics on
      bioavailability and bioaccumulation in the nematode Caenorhabditis elegans.
AB  - To investigate the impact of multiple cadmium exposure pathways on
      bioavailability and bioaccumulation, Caenorhabditis elegans were exposed to
      either dissolved cadmium or to both particulate (dietborne) and dissolved
      cadmium. The dietborne metal exposure scenarios included evaluations of two
      bacteria species (Escherichia coli and Arthrobacter globiformis), varying
      bacteria concentrations, artificial particles (with different surface functional
      groups or coated with lipopolysaccharides), as well as a mixture of both bacteria
      and artificial particles. Total cadmium concentration in the nematodes was used
      as a proxy for total metal accumulation. Internal cadmium availability was
      determined using the cadmium-responsive gene-1 (cdr-1) transcript level, as
      quantified by real-time polymerase chain reaction. Particle-associated exposure
      was the predominant contributor to cadmium bioavailability and bioaccumulation;
      however, no clear relationship between cdr-1 expression and cadmium body burden
      was observed. The quality and quantity of particles, rather than the total
      particle-associated metal load, was of primary importance in regulating cadmium
      uptake and accumulation. Nematodes exposed to cadmium-contaminated bacteria
      displayed significantly higher levels of cdr-1 expression relative to artificial
      particles. Furthermore, C. elegans displayed a statistically significant
      difference in cadmium accumulation patterns between the biotic diet, abiotic
      particles, and aqueous phase. Waterborne exposure caused an increase in total
      cadmium body burden following inhibition of the P-glycoprotein transport system
      in nematodes. This may suggest that cadmium taken up by the aqueous phase is
      detoxified preferentially by excretion.

PMID- 19159128
TI  - Mass recovery methods for trichloroethylene in plant tissue.
AB  - Monitoring expenses form a significant fraction of the costs associated with
      remediation of contaminated soil and groundwater sites. A novel monitoring method
      that could result in significant cost savings is the use of plants as monitoring
      devices; previous work indicates that plant tissue samples, especially trunk
      (core) and branch samples, can be used to delineate soil and groundwater plumes
      at phytoremediation sites. An important factor in reducing the uncertainty
      associated with this sampling method is development of a technique to analyze,
      both consistently and accurately, the chemicals stored in plant tissue samples.
      The present research presents a simple, robust, and inexpensive technique to
      recover most of the contaminant in plant branch tissue, irrespective of the age
      or species of the plant. Tricholoroethylene (TCE) was the chemical analyzed. A
      number of headspace and solvent extraction techniques in the literature were
      evaluated, including headspace extraction at different incubation times and
      temperatures and solvent extraction using hexane or hot methanol. Extraction
      using hot methanol was relatively fast, simple, and reliable; this method
      recovered more than 89% of the TCE present in branches of five different tree
      species.

PMID- 19159129
TI  - Janiceps conjoined twins with extreme asymmetry: case report with complete
      autopsy and histopathologic findings.
AB  - Conjoined twinning is a rare form of twinning, in which 2 bodies are attached,
      and is classified according to the anatomic place of attachment. An extremely
      rare form of conjoined twinning is janiceps conjoined twinning, in which 2 faces
      are attached but oriented in opposite directions. In this report, we present an
      unusual and difficult-to-classify case of conjoined male twins with partial
      duplication of craniofacial, upper oropharyngeal, and cardiac organs. We believe
      this to be one of the few reported cases of janiceps asymmetrus. We describe in
      detail the gross and microscopic pathology and offer some insights into the
      possible embryogenesis and distinction from the other rare form of conjoined
      twinning with facial duplication, diprosopus.

PMID- 19159131
TI  - When dreaming is believing: the (motivated) interpretation of dreams.
AB  - This research investigated laypeople's interpretation of their dreams.
      Participants from both Eastern and Western cultures believed that dreams contain
      hidden truths (Study 1) and considered dreams to provide more meaningful
      information about the world than similar waking thoughts (Studies 2 and 3). The
      meaningfulness attributed to specific dreams, however, was moderated by the
      extent to which the content of those dreams accorded with participants'
      preexisting beliefs--from the theories they endorsed to attitudes toward
      acquaintances, relationships with friends, and faith in God (Studies 3-6).
      Finally, dream content influenced judgment: Participants reported greater
      affection for a friend after considering a dream in which a friend protected
      rather than betrayed them (Study 5) and were equally reluctant to fly after
      dreaming or learning of a plane crash (Studies 2 and 3). Together, these results
      suggest that people engage in motivated interpretation of their dreams and that
      these interpretations impact their everyday lives.

PMID- 19159132
TI  - Contrast effects in spontaneous evaluations: a psychophysical account.
AB  - In the affective-priming paradigm, target stimuli are preceded by evaluatively
      polarized prime stimuli and then are to be classified as either good or bad as
      fast as possible. The typical and robust finding is assimilation: Primes
      facilitate the processing of evaluatively consistent targets relative to
      evaluatively inconsistent targets. Nevertheless, contrast effects have repeatedly
      been observed. The authors propose a new psychophysical account of normal
      (assimilative) and reversed (contrastive) priming effects and test new
      predictions derived from it in 5 studies: In Studies 1 and 2, the authors'
      account is shown to provide a better explanation of contrastive effects in a
      priming paradigm with two primes than the traditional attentional account does.
      Furthermore, as predicted by the new account, contrast effects emerge at an
      intermediate stimulus-onset asynchrony (SOA, Study 3) and even with short SOAs
      when target onset takes participants by surprise (Study 4). Finally, the use of
      extremely valenced primes triggers corrective efforts (Study 5) as predicted.
      Implications for priming measures of evaluative associations are discussed.

PMID- 19159133
TI  - Stereotype threat reinterpreted as a regulatory mismatch.
AB  - This research documents performance decrements resulting from the activation of a
      negative task-relevant stereotype. The authors combine a number of strands of
      work to identify causes of stereotype threat in a way that allows them to reverse
      the effects and improve the performance of individuals with negative task
      relevant stereotypes. The authors draw on prior work suggesting that negative
      stereotypes induce a prevention focus and on other research suggesting that
      people exhibit greater flexibility when their regulatory focus matches the reward
      structure of the task. This work suggests that stereotype threat effects emerge
      from a prevention focus combined with tasks that have an explicit or implicit
      gains reward structure. The authors find flexible performance can be induced in
      individuals who have a negative task-relevant stereotype by use of a losses
      reward structure. The authors demonstrate the interaction of stereotypes and the
      reward structure of the task with chronic stereotypes and Graduate Record
      Examination math problems (Experiment 1), and with primed stereotypes and a
      category learning task (Experiments 2A and 2B). The authors discuss implications
      of this research for other work on stereotype threat.

PMID- 19159134
TI  - Attentional processes in stereotype formation: a common model for category
      accentuation and illusory correlation.
AB  - Stereotype formation may be based on the exaggeration of real group differences
      (category accentuation) or the misperception of group differences that do not
      exist (illusory correlation). This research sought to account for both phenomena
      with J. K. Kruschke's (1996, 2001, 2003) attention theory of category learning.
      According to the model, the features of majority groups are learned earlier than
      the features of minority groups. In turn, the features that become associated
      with a minority are those that most distinguish it from the majority. This second
      process is driven by an attention-shifting mechanism that directs attention
      toward group-attribute pairings that facilitate differentiation of the two groups
      and may lead to the formation of stronger minority stereotypes. Five experiments
      supported this model as a common account for category accentuation and
      distinctiveness-based illusory correlation. Implications for the natures of
      stereotype formation, illusory correlation, and impression formation are
      discussed.

PMID- 19159135
TI  - Fostering partner dependence as trust insurance: the implicit contingencies of
      the exchange script in close relationships.
AB  - A model of the trust-insurance system is proposed to examine how people with low
      and high self-esteem cope with the interdependence dilemma posed by feeling
      inferior to a romantic partner. Feeling inferior automatically activates "if
      then" contingencies that link inferiority to the exchange script (i.e., partner
      qualities are evenly traded) and exchange script anxieties to reparative efforts
      to secure a partner's dependence. A daily diary study of newlyweds and 5
      experiments supported the model. Induced upward social comparisons to the partner
      activated exchange anxieties for low, but not high, self-esteem people. When
      implicitly primed, the exchange script heightened worries about being inferior
      and motivated behavioral efforts to increase the partner's dependence regardless
      of self-esteem. When consciously deliberated, the exchange script elicited
      dependence promotion only for low self-esteem people.

PMID- 19159136
TI  - Targets as perceivers: how people determine when they will be negatively
      stereotyped.
AB  - Research on stereotype threat has demonstrated that when targets are forced to
      contend with the threat of being negatively stereotyped, their academic
      performance suffers (C. M. Steele & J. Aronson, 1995). The present research
      explored how the targets of negative stereotypes determine when they must contend
      with this threat. Across 5 experiments, the authors manipulated both the
      possibility and probability that Black and female students would be stereotyped
      as unintelligent prior to taking an analytical test. Collectively, these
      experiments showed that these students contended with stereotype threat only when
      they perceived that it was both possible and probable that they would be
      negatively stereotyped. The authors discuss the implications of these findings on
      the experience of being the target of negative stereotypes and on the academic
      achievement of Blacks and women.

PMID- 19159137
TI  - This mood is familiar and I don't deserve to feel better anyway: mechanisms
      underlying self-esteem differences in motivation to repair sad moods.
AB  - Why are people with low self-esteem (LSE) less motivated than people with high
      self-esteem (HSE) to improve sad moods? The present research examined whether
      feelings of personal deservingness contribute to this difference. Four
      experiments with undergraduate participants involved a sad mood induction, a
      manipulation of personal deservingness, or both. Results suggested that (a) LSEs
      feel less deserving of positive outcomes and of positive moods than do HSEs, (b)
      feelings of personal deservingness can vary with the situation, and be lowered
      through reminders of social rejection and personal flaws, and (c) feeling
      relatively undeserving dampens LSEs', but not HSEs', motivation to repair sad
      moods. These results have implications for the emotion regulation, self-esteem,
      and social justice literatures.

PMID- 19159138
TI  - Fit to forgive: Exploring the interaction between regulatory focus, repentance,
      and forgiveness.
AB  - Three studies, using diverse methodologies and measures, were conducted to
      examine the role that the regulatory focus of an injured party and of a
      transgressor (E. T. Higgins, 1997, 2000) plays in explaining the relationship
      between repentance and forgiveness. The authors predicted that when a victim's
      regulatory focus (i.e., promotion vs. prevention) was congruent (i.e., fit) with
      the regulatory focus of a transgressor's repentance (i.e., promotion vs.
      prevention), there would be greater forgiveness compared with when there was
      incongruence (i.e., mismatch). Three studies supported these predictions. The
      results also confirmed one potential explanation for why apologies are not always
      successful at eliciting forgiveness, namely, feeling right. This research
      suggests that regulatory focus theory can help inform the scientific study of
      forgiveness and its related processes.

PMID- 19159139
TI  - The role of interpersonal perceptions in the prime-to-behavior pathway.
AB  - The present research suggests that biased interpersonal perceptions can mediate
      prime-to-behavior effects and introduces a new moderator for when such mediation
      will occur. Across 5 experiments, the authors provide evidence that priming
      effects on behavior in interpersonal contexts are mediated by social perceptions,
      but only when participants are focused on the other person. These effects occur
      when other-focus is primed (Experiment 1), when other-focus is high owing to the
      decision-making situation (Experiment 2), and when other-focus is dispositionally
      high (Experiment 3). Experiments 4 and 5 bring additional support for a biased
      perception account by ruling out an alternative behavior-perception link and
      showing that other-focus can moderate not only the mediating mechanism of prime
      to-behavior effects but also the behavioral effects themselves. The implications
      of these results for increasing understanding of behavioral priming effects in
      rich social contexts are discussed.

PMID- 19159140
TI  - Motivations for prevention or promotion following social exclusion: being
      rejected versus being ignored.
AB  - Social exclusion evokes powerful motivations and emotions. The present studies
      examined how these motivations and emotions might differ following exclusion that
      is explicit, active, and direct (i.e., when one is rejected) versus implicit,
      passive, and indirect (i.e., when one is ignored). It was hypothesized that being
      rejected should produce a sense of social loss and lead to more prevention
      focused responses, including withdrawal from social contact, thoughts about
      actions one should not have taken, and increased feelings of agitation. In
      contrast, being ignored should produce a sense of failure to achieve social gain
      and lead to more promotion-focused responses, including reengagement in social
      contact, thoughts about actions one should have taken, and increased feelings of
      dejection. These hypotheses were supported across 4 studies in which people
      recalled or underwent experiences of being rejected or ignored. Past research on
      active versus passive exclusion is reexamined and found to be consistent with
      these hypotheses as well.

PMID- 19159141
TI  - Distributing prejudice unequally: do Whites direct their prejudice toward
      strongly identified minorities?
AB  - Across 6 studies, Whites expressed more negative attitudes toward strongly
      identified racial minorities than toward weakly identified minorities. Whites who
      personally endorsed worldviews that legitimize the status hierarchy were
      particularly likely to express negative attitudes toward strongly identified
      minorities relative to weakly identified minorities, whereas Whites who
      personally rejected status-legitimizing worldviews displayed the opposite
      pattern. In addition, Whites' biases against strongly identified minorities
      dissipated when strongly identified minorities expressed strong endorsement of
      status-legitimizing worldviews. These studies suggest that Whites do not
      distribute their prejudicial attitudes equally among all members of minority
      groups and that some subsets of minorities (the strongly identified) might bear
      the brunt of racial prejudice.

PMID- 19159142
TI  - Not all conscientiousness scales change alike: a multimethod, multisample study
      of age differences in the facets of conscientiousness.
AB  - Previous research has shown that traits from the domain of conscientiousness tend
      to increase with age. However, previous research has not tested whether all
      aspects of conscientiousness change with age. The present research tests age
      differences in multiple facets of conscientiousness (industriousness,
      orderliness, impulse control, reliability, and conventionality) using multiple
      methods and multiple samples. In a community sample (N = 274) and a
      representative statewide sample (N = 613) of 18- to 94-year-olds, self-reported
      industriousness, impulse control, and reliability showed age differences from
      early adulthood to middle age, whereas orderliness did not. The transition into
      late adulthood was characterized by increases in impulse control, reliability,
      and conventionality. In contrast, age differences in observer-rated personality
      occurred mainly in older adulthood. Age differences held across both ethnicity
      and levels of socioeconomic status.

PMID- 19159143
TI  - Similarity and assumed similarity in personality reports of well-acquainted
      persons.
AB  - The authors obtained self- and observer reports of personality from pairs of well
      acquainted college students. Consistent with previous findings, results of Study
      1 showed strong cross-source agreement for all 6 HEXACO personality factors (rs
      approximately .55). In addition, the authors found modest levels of similarity (r
      approximately .25) between dyad members' self-reports on each of 2 dimensions,
      Honesty-Humility and Openness to Experience. For these same 2 factors, dyad
      members' self-reports were correlated with their observer reports of the other
      dyad member (r approximately .40), thus indicating moderately high assumed
      similarity. In Study 2, Honesty-Humility and Openness to Experience were the 2
      personality factors most strongly associated with the 2 major dimensions of
      personal values, which also showed substantial assumed similarity. In Study 3,
      assumed similarity was considerably stronger for close friends than for nonfriend
      acquaintances. Results suggest that assumed similarity for Honesty-Humility and
      Openness to Experience reflects a tendency to overestimate one's similarity to
      persons with whom one has a close relationship, but only on those personality
      characteristics whose relevance to values gives them central importance to one's
      identity.

PMID- 19159144
TI  - Thine own self: true self-concept accessibility and meaning in life.
AB  - A number of philosophical and psychological theories suggest the true self is an
      important contributor to well-being. The present research examined whether the
      cognitive accessibility of the true self-concept would predict the experience of
      meaning in life. To ensure that any observed effects were due to the true self
      concept rather than to the self-concept more generally, the authors used actual
      self-concept accessibility as a control variable in all studies. True and actual
      self-concepts were defined as including those traits that are enacted around
      close others vs. most others (Studies 1 through 3) or as traits that refer to
      "who you really are" vs. "who you are during most of your activities" (Studies 4
      and 5), respectively. Studies 1, 2, and 4 showed that individual differences in
      true self-concept accessibility, but not differences in actual self-concept
      accessibility, predicted meaning in life. Studies 3 and 5 showed that priming
      traits related to the true self-concept enhanced perceptions of meaning in life.
      Implications for the study of the true self-concept and authenticity are
      discussed.

PMID- 19159145
TI  - Why do dominant personalities attain influence in face-to-face groups? The
      competence-signaling effects of trait dominance.
AB  - Individuals high in the personality trait dominance consistently attain high
      levels of influence in groups. Why they do is unclear, however, because most
      group theories assert that people cannot attain influence simply by behaving
      assertively and forcefully; rather, they need to possess superior task abilities
      and leadership skills. In the present research, the authors proposed that
      individuals high in trait dominance attain influence because they behave in ways
      that make them appear competent--even when they actually lack competence. Two
      studies examined task groups using a social relations analysis of peer
      perceptions (D. A. Kenny & L. LaVoie, 1984). The authors found that individuals
      higher in trait dominance were rated as more competent by fellow group members,
      outside peer observers, and research staff members, even after controlling for
      individuals' actual abilities. Furthermore, frequency counts of discrete
      behaviors showed that dominance predicts the enactment of competence-signaling
      behaviors, which in turn predicts peer ratings of competence. These findings
      extend researchers' understanding of trait dominance, hierarchies in groups, and
      perceptions of competence and abilities.

PMID- 19159146
TI  - Superadditive memory strength for item and source recognition: the role of
      hierarchical relational binding in the medial temporal lobe.
AB  - Source memory depends on our ability to recollect contextual information--such as
      the time, place, feelings, and thoughts associated with a past event. It is
      acknowledged that the medial temporal lobe (MTL) plays a critical role in binding
      such episodic features. Yet, controversy exists over the nature of MTL binding-
      whether it contributes specifically to source recollection or whether it
      contributes equally to both item familiarity and source recollection. To resolve
      this issue, the authors propose that the MTL acts to bind contextual features
      through a process of hierarchical relational binding. That is, by way of multiple
      levels of associative bindings (i.e., bindings of bindings), the MTL links
      episodic features in a superadditive manner. To account for this binding feature,
      the authors develop a recognition model that includes positively skewed
      distributions of memory strength. Such skewed distributions can account for many
      empirical findings and regularities of both item familiarity and source
      recollection.

PMID- 19159124
TI  - Statin adverse effects : a review of the literature and evidence for a
      mitochondrial mechanism.
AB  - HMG-CoA reductase inhibitors (statins) are a widely used class of drug, and like
      all medications, have potential for adverse effects (AEs). Here we review the
      statin AE literature, first focusing on muscle AEs as the most reported problem
      both in the literature and by patients. Evidence regarding the statin muscle AE
      mechanism, dose effect, drug interactions, and genetic predisposition is
      examined. We hypothesize, and provide evidence, that the demonstrated
      mitochondrial mechanisms for muscle AEs have implications to other nonmuscle AEs
      in patients treated with statins. In meta-analyses of randomized controlled
      trials (RCTs), muscle AEs are more frequent with statins than with placebo. A
      number of manifestations of muscle AEs have been reported, with rhabdomyolysis
      the most feared. AEs are dose dependent, and risk is amplified by drug
      interactions that functionally increase statin potency, often through inhibition
      of the cytochrome P450 3A4 system. An array of additional risk factors for statin
      AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability,
      such as metabolic syndrome factors, thyroid disease, and genetic mutations linked
      to mitochondrial dysfunction. Converging evidence supports a mitochondrial
      foundation for muscle AEs associated with statins, and both theoretical and
      empirical considerations suggest that mitochondrial dysfunction may also underlie
      many nonmuscle statin AEs. Evidence from RCTs and studies of other designs
      indicates existence of additional statin-associated AEs, such as cognitive loss,
      neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. Physician
      awareness of statin AEs is reportedly low even for the AEs most widely reported
      by patients. Awareness and vigilance for AEs should be maintained to enable
      informed treatment decisions, treatment modification if appropriate, improved
      quality of patient care, and reduced patient morbidity.

PMID- 19159147
TI  - Structured statistical models of inductive reasoning.
AB  - Everyday inductive inferences are often guided by rich background knowledge.
      Formal models of induction should aim to incorporate this knowledge and should
      explain how different kinds of knowledge lead to the distinctive patterns of
      reasoning found in different inductive contexts. This article presents a Bayesian
      framework that attempts to meet both goals and describes [corrected] 4
      applications of the framework: a taxonomic model, a spatial model, a threshold
      model, and a causal model. Each model makes probabilistic inferences about the
      extensions of novel properties, but the priors for the 4 models are defined over
      different kinds of structures that capture different relationships between the
      categories in a domain. The framework therefore shows how statistical inference
      can operate over structured background knowledge, and the authors argue that this
      interaction between structure and statistics is critical for explaining the power
      and flexibility of human reasoning.

PMID- 19159148
TI  - Modeling confidence and response time in recognition memory.
AB  - A new model for confidence judgments in recognition memory is presented. In the
      model, the match between a single test item and memory produces a distribution of
      evidence, with better matches corresponding to distributions with higher means.
      On this match dimension, confidence criteria are placed, and the areas between
      the criteria under the distribution are used as drift rates to drive racing
      Ornstein-Uhlenbeck diffusion processes. The model is fit to confidence judgments
      and quantile response times from two recognition memory experiments that
      manipulated word frequency and speed versus accuracy emphasis. The model and data
      show that the standard signal detection interpretation of z-transformed receiver
      operating characteristic (z-ROC) functions is wrong. The model also explains
      sequential effects in which the slope of the z-ROC function changes by about 10%
      as a function of the prior response in the test list.

PMID- 19159149
TI  - Signal detection with criterion noise: applications to recognition memory.
AB  - A tacit but fundamental assumption of the theory of signal detection is that
      criterion placement is a noise-free process. This article challenges that
      assumption on theoretical and empirical grounds and presents the noisy decision
      theory of signal detection (ND-TSD). Generalized equations for the isosensitivity
      function and for measures of discrimination incorporating criterion variability
      are derived, and the model's relationship with extant models of decision making
      in discrimination tasks is examined. An experiment evaluating recognition memory
      for ensembles of word stimuli revealed that criterion noise is not trivial in
      magnitude and contributes substantially to variance in the slope of the
      isosensitivity function. The authors discuss how ND-TSD can help explain a number
      of current and historical puzzles in recognition memory, including the
      inconsistent relationship between manipulations of learning and the
      isosensitivity function's slope, the lack of invariance of the slope with
      manipulations of bias or payoffs, the effects of aging on the decision-making
      process in recognition, and the nature of responding in remember-know decision
      tasks. ND-TSD poses novel, theoretically meaningful constraints on theories of
      recognition and decision making more generally, and provides a mechanism for
      rapprochement between theories of decision making that employ deterministic
      response rules and those that postulate probabilistic response rules.

PMID- 19159150
TI  - The law of categorical judgment (Corrected) and the interpretation of changes in
      psychophysical performance.
AB  - Signal detection theory (SDT) makes the frequently challenged assumption that
      decision criteria have no variance. An extended model, the Law of Categorical
      Judgment, relaxes this assumption. The long accepted equation for the law,
      however, is flawed: It can generate negative probabilities. The correct equation,
      the Law of Categorical Judgment (Corrected), is derived; the SDT rating model is
      a special case. An example shows how to invert the Law of Categorical Judgment
      (Corrected) numerically, thereby extracting estimates of signal and criterion
      density parameters and their confidence limits from rating data. The SDT rating
      model predicts linear Zeta-transformed operating characteristics (ZetaROCs),
      whereas the new equation can produce nonlinear ZetaROCs. For single-criterion
      experiments (e.g., yes/no, two-alternative forced choice), however, the corrected
      law yields identical d' values and linear ZetaROCs whether criterion variance is
      nonzero or zero. Performance differences observed in such experiments can always
      be attributed equally well to altered perceptual sensitivity or to modified
      criterion variance. The Law of Categorical Judgment (Corrected) offers to resolve
      this ambiguity through rating experiments.

PMID- 19159152
TI  - Failure to recall.
AB  - Mathematical analysis shows that if the pattern of rehearsal in free-recall
      experiments (of necessity, the pattern observed when participants rehearse aloud)
      be continued without any further interruption by stimuli (as happens during
      recall), it terminates with the retrieval of the same 1 word over and over again.
      Such a terminal state is commonly reached before some of the words in the list
      have been retrieved even once; those words are not recalled. The 1 minute
      frequently allowed for recall in free-recall experiments is ample time for
      retrieval to seize up in this way. The author proposes a model that represents
      the essential features of the pattern of rehearsal; validates that model by
      reference to the overt rehearsal data from B. B. Murdock, Jr., and J. Metcalfe
      (1978) and the recall data from B. B. Murdock, Jr., and R. Okada (1970);
      demonstrates the long-term properties of continued sequences of retrievals and,
      also, a fundamental relation linking recall to the total time of presentation;
      and, finally, compares failure to recall in free-recall experiments with
      forgetting in general.

PMID- 19159151
TI  - A context maintenance and retrieval model of organizational processes in free
      recall.
AB  - The authors present the context maintenance and retrieval (CMR) model of memory
      search, a generalized version of the temporal context model of M. W. Howard and
      M. J. Kahana (2002a), which proposes that memory search is driven by an
      internally maintained context representation composed of stimulus-related and
      source-related features. In the CMR model, organizational effects (the tendency
      for related items to cluster during the recall sequence) arise as a consequence
      of associations between active context elements and features of the studied
      material. Semantic clustering is due to longstanding context-to-item
      associations, whereas temporal clustering and source clustering are both due to
      associations formed during the study episode. A behavioral investigation of the
      three forms of organization provides data to constrain the CMR model, revealing
      interactions between the organizational factors. Finally, the authors discuss the
      implications of CMR for their understanding of a broad class of episodic memory
      phenomena and suggest ways in which this theory may guide exploration of the
      neural correlates of memory search.

PMID- 19159153
TI  - Pseudocontingencies: an integrative account of an intriguing cognitive illusion.
AB  - The term pseudocontingency (PC) denotes the logically unwarranted inference of a
      contingency between 2 variables X and Y from information other than pairs of xi,
      yi observations, namely, the variables' univariate base rates as assessed in 1 or
      more ecological contexts. The authors summarize recent experimental evidence
      showing that PCs can play a pivotal role in many areas of judgment and decision
      making. They argue that the exploitation of the informational value of base rates
      underlying PCs offers an alternative perspective on many phenomena in the realm
      of adaptive cognition that have been studied in isolation so far. Although PCs
      can lead to serious biases under some conditions, they afford an efficient
      strategy for inductive inference making in probabilistic environments that render
      base-rate information, rather than genuine covariation information, readily
      available.

PMID- 19159154
TI  - Putting it all together: a unified account of word recognition and reaction-time
      distributions.
AB  - R. Ratcliff, P. Gomez, and G. McKoon (2004) suggested much of what goes on in
      lexical decision is attributable to decision processes and may not be
      particularly informative about word recognition. They proposed that lexical
      decision should be characterized by a decision process, taking the form of a
      drift-diffusion model (R. Ratcliff, 1978), that operates on the output of lexical
      model. The present article argues that the distinction between perception and
      decision making is unnecessary and that it is possible to give a unified account
      of both lexical processing and decision making. This claim is supported by formal
      arguments and reinforced by simulations showing how the Bayesian Reader model (D.
      Norris, 2006) can be extended to fit the data on reaction time distributions
      collected by Ratcliff, Gomez, and McKoon simply by adding extra sources of noise.
      The Bayesian Reader gives an integrated explanation of both word recognition and
      decision making, using fewer parameters than the diffusion model. It can be
      thought of as a Bayesian diffusion model, which subsumes Ratcliff's drift
      diffusion model as a special case.

PMID- 19159155
TI  - On the biological plausibility of grandmother cells: implications for neural
      network theories in psychology and neuroscience.
AB  - A fundamental claim associated with parallel distributed processing (PDP)
      theories of cognition is that knowledge is coded in a distributed manner in mind
      and brain. This approach rejects the claim that knowledge is coded in a localist
      fashion, with words, objects, and simple concepts (e.g. "dog"), that is, coded
      with their own dedicated representations. One of the putative advantages of this
      approach is that the theories are biologically plausible. Indeed, advocates of
      the PDP approach often highlight the close parallels between distributed
      representations learned in connectionist models and neural coding in brain and
      often dismiss localist (grandmother cell) theories as biologically implausible.
      The author reviews a range a data that strongly challenge this claim and shows
      that localist models provide a better account of single-cell recording studies.
      The author also contrast local and alternative distributed coding schemes (sparse
      and coarse coding) and argues that common rejection of grandmother cell theories
      in neuroscience is due to a misunderstanding about how localist models behave.
      The author concludes that the localist representations embedded in theories of
      perception and cognition are consistent with neuroscience; biology only calls
      into question the distributed representations often learned in PDP models.

PMID- 19159156
TI  - What is self-specific? Theoretical investigation and critical review of
      neuroimaging results.
AB  - The authors propose a paradigm shift in the investigation of the self.
      Synthesizing neuroimaging results from studies investigating the self, the
      authors first demonstrate that self-relatedness evaluation involves a wide
      cerebral network, labeled E-network, comprising the medial prefrontal cortex,
      precuneus, temporoparietal junction, and temporal poles. They further show that
      this E-network is also recruited during resting state, others' mind reading,
      memory recall, and reasoning. According to these data, (a) the profile of
      activation of the E-network demonstrates no preference for the self, and (b) the
      authors suggest that activity in this network can be explained by the involvement
      of cognitive processes common to all the tasks recruiting it: inferential
      processing and memory recall. On this basis, they conclude that standard ways to
      tackle the self by considering self-evaluation do not target the self in its
      specificity. Instead, they argue that self-specificity characterizes the
      subjective perspective, which is not intrinsically self-evaluative but rather
      relates any represented object to the representing subject. They further propose
      that such self-specific subject-object relation is anchored to the sensorimotor
      integration of efference with reafference (i.e., the motor command of the
      subject's action and its sensory consequence in the external world).

PMID- 19159158
TI  - Competition between multiple causes of a single outcome in causal reasoning.
AB  - A strong positive predictor of an outcome modulates the causal judgments of a
      moderate predictor. To study the empirical basis of this modulation, we compared
      treatments with one and with two strong competing (i.e., modulating) causes. This
      allowed us to vary the frequency of outcome occurrences or effects paired with
      the predictors. We investigated causal competition between positive predictors
      (those signaling the occurrence of the outcome), between negative predictors
      (those signaling the absence of the outcome) and between predictors of opposite
      polarity (positive and negative). The results are consistent with a contrast
      rather than a reduced associative strength or conditional contingency account,
      because a strong predictor of opposite polarity enhances rather than reduces
      causal estimates of moderate predictors. In addition, we found competition
      effects when the strong predictor predicted fewer outcome occurrences than the
      moderate predictor, thus implying that cue competition is, at least sometimes, a
      consequence of contingency rather than total cue-outcome pairings.

PMID- 19159159
TI  - Human risky choice: delay sensitivity depends on reinforcer type.
AB  - The present study was designed to help bridge the methodological gap between
      human and nonhuman animal research in delay-based risky choice. In Part 1, 4
      adult human subjects made repeated choices between variable-time and fixed-time
      schedules of 30-s video clips. Both alternatives had equal mean delays of 15 s,
      30 s, or 60 s. Three of 4 subjects strongly preferred the variable-delay
      alternative across all conditions. In Part 2, these 3 subjects were then provided
      pairwise choices between 2 variable-time schedules with different delay
      distributions. Subjects generally preferred the variable-delay distributions with
      a higher probability of short-reinforcer delays, consistent with accounts based
      on nonlinear discounting of delayed reinforcement. There was only weak
      correspondence between experimental results and verbal reports. The overall
      pattern of results is inconsistent with prior risky choice research with human
      subjects but is consistent with prior results with nonhuman subjects, suggesting
      that procedural differences may be a critical factor determining risk-sensitivity
      across species.

PMID- 19159160
TI  - Chimpanzees solve the trap problem when the confound of tool-use is removed.
AB  - The trap-tube problem is difficult for chimpanzees to solve; in several studies
      only 1 to 2 subjects learn the solution. The authors tested eight chimpanzees on
      a non-tool-using version of the problem to investigate whether the inclusion of a
      tool in previous tests of the trap problem may have masked the ability of
      chimpanzees to solve it. All eight learned to avoid the trap, in 40 to 100
      trials. One transferred to two tasks that had no visual cue in common. The
      authors examined the performance of 15 chimpanzees on a new task in a 2 x 2
      design: seven had experience on the two-trap box, eight had not; half of each
      group was tested with a tool, half without one. An ANOVA revealed a significant
      effect of tool-inclusion and experience (p < .05). Our results show that
      including a tool in the trap problem profoundly affects the ability of
      chimpanzees to solve it. With regard to what the chimpanzees had learned, the
      results support the notion that rather than using the available stimuli as
      arbitrary cues, the subjects had encoded information about functional properties.

PMID- 19159161
TI  - Progressive ratio schedules of reinforcement.
AB  - Pigeons' pecks produced grain under progressive ratio (PR) schedules, whose
      response requirements increased systematically within sessions. Experiment 1
      compared arithmetic (AP) and geometric (GP) progressions. Response rates
      increased as a function of the component ratio requirement, then decreased
      linearly (AP) or asymptotically (GP). Experiment 2 found the linear decrease in
      AP rates to be relatively independent of step size. Experiment 3 showed pausing
      to be controlled by the prior component length, which predicted the differences
      between PR and regressive ratio schedules found in Experiment 4. When the longest
      component ratios were signaled by different key colors, rates at moderate ratios
      increased, demonstrating control by forthcoming context. Models for response rate
      and pause duration based on Bizo and Killeen (1997) described performance on AP
      schedules; GP schedules required an additional parameter representing the
      contextual reinforcement.

PMID- 19159162
TI  - A comparison of empirical and theoretical explanations of temporal
      discrimination.
AB  - The empirical goals were to describe the behavior of rats trained on multiple
      temporal discriminations and to use these descriptions to predict behavior
      observed under new training conditions. The theoretical goals were to fit a
      quantitative theory to behavior from one training condition, estimate parameters
      for the intervening perception, memory, and decision processes, and use these
      parameters to predict behavior observed under new conditions. Twenty-four rats
      were trained on a multiple-peak-interval procedure with two stimuli that were
      presented individually (Stimulus A and B), or in compound (Compound AB); either
      different responses (Experiment 1) or the same response (Experiment 2) were
      reinforced during the presentations of Stimulus A, Stimulus B, and Compound AB.
      The patterns of correct and stimulus-error responses during Stimulus A and
      Stimulus B (Experiment 1) were used as elements that, with summation rules,
      predicted behavior under new conditions (Compound AB, Experiment 1; Stimulus A,
      Stimulus B, and Compound AB, Experiment 2). A comparison of the success of the
      empirical and theoretical goals supported the use of a quantitative theory of
      behavior to explain the data.

PMID- 19159163
TI  - Differential outcomes enhance accuracy of delayed matching to sample but not
      resistance to change.
AB  - Three experiments assessed the relation between the differential outcomes effect
      and resistance to change of delayed matching-to-sample performance. Pigeons
      produced delayed matching-to-sample trials by responding on variable interval
      schedules in two components of a multiple schedule. In the same-outcome
      component, the probability of reinforcement was the same for both samples (.9 in
      Experiments 1 and 2, .5 in Experiment 3); in the different-outcomes component,
      the probability of reinforcement was .9 for one sample and .1 for the other. In
      all three experiments, the forgetting functions in the different-outcomes
      component were higher and shallower than in the same-outcomes component. When
      total reinforcement was greater in the same-outcomes component (Experiments 1 and
      2), resistance to disruption by prefeeding, intercomponent food, extinction, or
      flashing lights typically was greater in that component. In Experiment 3, when
      total reinforcement was equated, resistance to disruption was similar across
      components. Thus, the level and slope of forgetting functions depended on
      differential reinforcement correlated with the samples, but the resistance to
      change of forgetting functions depended on total reinforcement in a component.
      Both aspects of the results can be explained by a model of delayed matching to
      sample performance.

PMID- 19159164
TI  - Integration of geometric with luminance information in the rat: evidence from
      within-compound associations.
AB  - In two experiments, rats first received preexposure to a rectangular arena in
      which the geometrically equivalent corner pairs (G1 and G2) were coincident with
      different luminance characteristics (C1 and C2, respectively). In Experiment 1,
      rats were then placed in a uniform gray rectangular arena where food was located
      in one geometrically equivalent pair of corners (G1), but not another (G2).
      Finally, rats were tested in a square arena with C1 and C2 and preferred to
      search in C1 rather than C2. In Experiment 2, following preexposure to G1C1 and
      G2C2, rats received pairings of C1 with food and C2 with no food in a square
      arena. During testing, rats preferred to search in G1 rather than G2 in a gray
      rectangular arena. These results demonstrate that reciprocal within-compound
      associations develop between geometric and luminance information and thereby
      challenge the view that there is a dedicated geometric module that is
      impenetrable to information that is not geometric.

PMID- 19159165
TI  - Between-cue associations influence searching for a hidden goal in an environment
      with a distinctive shape.
AB  - In Experiment 1 rats had to escape from a kite-shaped pool by swimming to a
      submerged escape platform in a right-angled corner. The two walls creating this
      corner were white and the two walls creating the opposite, incorrect, right
      angled corner were black. The rats were then trained in a square pool with two
      white walls forming one corner and two black walls forming the opposite corner.
      The platform was in the white corner for a consistent group and the black corner
      for an inconsistent group. A test in an entirely white kite revealed a stronger
      preference for the correct than the incorrect corner in the consistent but not
      the inconsistent group. This outcome is attributed to the formation of
      associations between geometric cues, provided by the shape of the pool, and the
      color of the walls. The results were replicated in a second experiment in which
      the walls of the test pool were the same color as the incorrect corner during
      initial training.

PMID- 19159166
TI  - Generalized auditory same-different discrimination by pigeons.
AB  - Three pigeons were trained in a successive same/different (S/D) procedure using
      compound auditory stimuli (pitch/timbre combinations). Using a go/no-go
      procedure, pigeons successfully learned to discriminate between sequences of
      either all same (AAAA...or BBBB...) or all different (ABCD...) sequences
      consisting of 12 sounds. Both pitch and timbre were subsequently established as
      controlling dimensions. Transfer tests with novel stimuli revealed a generalized
      basis for the discrimination (novel pitch/timbre combinations, novel pitches,
      novel instruments, and complex natural & man-made sounds). These results indicate
      for the first time that pigeons can learn generalized same/different
      discriminations in a nondominant modality. When combined with earlier visual
      results, they support a qualitative similarity among birds and primates in their
      capacity to judge this type of fundamental stimulus relation across different
      modalities.

PMID- 19159167
TI  - Implicit chaining in cotton-top tamarins (Saguinus oedipus).
AB  - In implicit learning, human subjects are exposed to patterned information, but
      they are not informed about the pattern. Typically, they demonstrate learning of
      that pattern, but little awareness of the experimental contingencies. In a
      nonhuman analog of this procedure, two cotton-top tamarins (Saguinus oedipus)
      were presented with a five-element chain that consisted of the same icon
      presented serially at different locations on a touchscreen. The tamarins had to
      touch the icon at each location to advance the chain and receive reinforcement at
      the end of the chain. One element of the chain was never differentially
      reinforced in the presence of another element, as is typically done in transitive
      inference and serial chaining studies. Following training, the tamarins were
      tested for their knowledge of the chain using pairwise tests that are common in
      transitive inference and serial chaining experiments, and a random test, common
      in some types of implicit learning, in which the sequence of elements was
      randomized. The results of both tests revealed that the tamarins appreciated the
      ordinal position of the elements composing the chain, although reinforcement had
      not been dependent on that knowledge.

PMID- 19159168
TI  - Evidence for a hierarchical structure underlying avoidance behavior.
AB  - In studies on avoidance learning, a warning signal is followed by an aversive
      unconditioned stimulus unless the participant performs a designated response. The
      authors examined whether avoidance behavior can be based on hierarchical
      knowledge, that is, knowledge about the conditions under which certain relations
      hold. In the present study, a single avoidance response had different effects
      depending on the nature of the warning signal. Results showed that participants
      acquired this hierarchical knowledge and used it to avoid negative outcomes. The
      results are in line with an occasion setting account of avoidance learning and
      can be explained also by a modified version of Lovibond's (2006) account of
      avoidance learning.

PMID- 19159169
TI  - [Adalimumab in Crohn's disease - data from real life].

PMID- 19159170
TI  - [Adalimumab induction and maintenance therapy for Crohn's disease. An open-label
      study].
AB  - BACKGROUND: adalimumab has been shown in placebo-controlled clinical trials and
      uncontrolled studies to be effective in luminal and perianal fistulizing CD.
      OBJECTIVE: to evaluate the efficacy and safety of adalimumab for induction and
      maintenance therapy in CD. METHODS: twenty-two patients with CD treated with
      adalimumab (16 for luminal disease and 6 for active perianal fistulizing disease)
      were included. Twenty-one patients had previously received IFX. All patients
      received induction therapy with 160 mg s.c. at week 0, and 80 mg s.c. at week 2.
      Responders received maintenance therapy with 40 mg s.c. every 14 days. Response
      was assessed at 4 weeks after the initial dose, and classified as remission,
      partial response, or non-response. RESULTS: after induction, 25% of patients with
      luminal disease had a complete remission, and 56.3% had a partial response.
      Clinical response was maintained in 71.6% of patients at 1 year, in 53.7% at 18
      months, and in 35.8% at 48 months. No differences in response were observed
      between patients with hypersensitivity reactions or loss of response to IFX.All
      patients with perianal fistulizing disease (n = 6) had been previously treated
      with IFX. After induction 16.7% entered remission, and 66.7% had a partial
      response. All patients maintained remission or response over time, with a median
      follow-up of 15 months. CONCLUSIONS: adalimumab is an effective and safe
      treatment for the induction and maintenance of response in luminal and perianal
      fistulizing CD. These results confirm that the findings obtained in controlled
      clinical trials are reproducible in clinical practice.

PMID- 19159171
TI  - [Natural history of hepatocellular carcinoma in a cohort of pacients from a
      county hospital].
AB  - BACKGROUND: hepatocellular carcinoma (HCC) is a cancer with high incidence and
      mortality. OBJECTIVE: our aim was to describe the natural history of a patient
      cohort with HCC, and to identify the factors associated with survival. PATIENTS
      AND METHODS: a retrospective and descriptive study of patients diagnosed with HCC
      between 1995 and 2002. Qualitative variables were expressed as frequencies and
      percentages. Quantitative variables were expressed as medians and standard
      deviations. Survival was calculated using the Kaplan-Meier method and log rank.
      RESULTS: a total of 154 patients were analyzed. The men-to-women ratio was 2.9/1.
      Mean age was 68 +/- 9 years. 82% of patients died during a median follow-up of 28
      months. Median survival was 21.5 months (95% CI: 16.98-26.04). Curative treatment
      was done in 40.3% of diagnosed patients, and 59.7% of patients received
      palliative treatment. Factors associated with survival were: ascites, number of
      lesions at diagnosis, and curative treatment. No statistical differences were
      found for the next factors: age, sex, etiology of cirrhosis, and Child-Pugh stage
      at diagnosis. CONCLUSIONS: factors associated with low survival in patients with
      HCC were ascites and number of lesions. Curative treatment is associated with a
      higher survival when compared to palliative treatment.

PMID- 19159172
TI  - [Liver injury induced by "natural remedies": an analysis of cases submitted to
      the Spanish Liver Toxicity Registry].
AB  - BACKGROUND: toxic liver damage associated with the use of natural remedies is a
      growing health problem. OBJECTIVES: to analyze the demographics, and clinical and
      epidemiological characteristics of patients developing liver injury related to
      these remedies. PATIENTS AND METHODS: all DILI cases associated with the use of
      herbal remedies (HR) or dietary supplements (DS) submitted to the Spanish
      Registry were analyzed. Type of liver damage, severity, and outcome were
      specifically evaluated. RESULTS: thirteen cases out of 521 DILI cases (2%)
      submitted to the Spanish Liver Toxicity Registry between 1994 and 2006 were
      related to HR/DS, which ranked as the 10th therapeutic group with a greater
      number of cases and above pain killers, anxiolytics, and antipsychotic drugs.
      Nine patients (69%) were female (mean age 45 years). Nine cases (69%) had
      jaundice at presentation. The predominating type of liver damage was
      hepatocellular (12; 92%), and 31% of cases exhibited the common features of
      hypersensitivity. Camellia sinensis (3, 23%) was the main causative herb,
      followed by Rhamnus purshianus and isoflavones (Fitosoja(R), Biosoja(R)) (2 cases
      each, 15%). Three cases (23%) were rechallenged with the offending product.
      CONCLUSIONS: the incidence of hepatic damage related to HR/DS is not so rare, the
      most common profile of affected patients being a woman with acute hepatocellular
      hepatitis. Low suspicion regarding the putative role of herbs in hepatotoxicity
      makes diagnosis more difficult, and probably increases the incidence of
      inadvertent rechallenge in these patients.

PMID- 19159173
TI  - [Gastrointestinal stromal tumors - a retrospective study of 43 cases].
AB  - BACKGROUND: gastrointestinal stromal tumors (GISTs) are rare (10 to 20/million).
      They exist in the whole digestive system and its surroundings, and are most
      common in the stomach (70%), followed by the small intestine (20-25%), colon and
      rectum (5%), and esophagus ( < 5%). Their clinical presentation varies from
      small, incidentally found nodules to large and aggressive tumors. Nowadays GISTs
      are classified according to Fletcher s classification. OBJECTIVE: to review the
      features of our GIST population. METHODS: a retrospective study of GIST patients
      identified by immunohistochemical criteria, from 1997 to December 2007, and
      classified according to Fletcher s criteria. RESULTS: 43 patients were included
      (24 men, 19 women) with a mean age of 62.7 years. Gastric GISTs (20 cases,
      46.5%), small intestine GISTs (18 cases, 41.9%); in 5 cases metastases of occult
      tumors were found. Eighteen cases had no symptoms. Tumors were classified
      according to Fletcher s criteria as high-risk (n = 19), intermediate-risk (n =
      7), low-risk (n = 12), and indeterminate-risk (n = 5). Death occurred in 10
      patients, and 13 patients had metastatic disease. CONCLUSIONS: our results are in
      accordance with the world literature, in which a majority of cases are men with
      gastric tumors. The 5-year survival rate was 42%. Fletcher s criteria were easily
      applicable criteria and could predict tumor behavior.

PMID- 19159174
TI  - [Acute esophageal necrosis. An underdiagnosed disease].
AB  - Acute esophageal necrosis is a rare disorder, and its etiology is unknown, the
      mechanism of damage being usually multifactorial and secondary to ischemic
      compromise, acute gastric outlet obstruction, and malnutrition. Endoscopic
      findings show circumferential black discoloration of the distal esophagus with
      proximal extension ending sharply at the gastroesophageal junction, which is the
      most common presentation. Prognosis depends on comorbid illnesses. In this study
      we analyze all cases reported in a retrospective analysis over a 2-year period to
      define risk factors, clinical presentation, endoscopic features, histological
      appearance, treatment and outcome. Our department has recorded 7 cases from 6,003
      endoscopies performed in the last 2 years. The finding of a "black esophagus"
      represented 0.11% of cases.

PMID- 19159175
TI  - [Prevalence and treatment of oncologic disease in the elderly --an impeding
      challenge].
AB  - Life expectancy in Spain has more than duplicated during the last 20th Century,
      and is currently 75 years for men and 83 years for women. Predictions on the
      evolution of the National and global population anticipate a demographic shock in
      Spain when individuals older than 65 years eventually make up more than 33.5% of
      the Spanish population by year 2050. It is known that cancer is directly related
      with age, and that it is a disease of older people -at least 60% of all cancers
      are diagnosed in patients older than 65 years. The older people group is the most
      important group of patients in oncologic practice today. Predictions on the aging
      of the Spanish population show that cancer in the aging patient and its treatment
      must be considered a first-line health problem. The diagnosis of cancer is not
      associated with death in the majority of patients. Sixty percent of cancers are
      globally cured or chronified. This advanced prognosis has its toll not only in
      the expectancy of treatment but also in subsequent follow-up and post-treatment
      adverse effects that can be generated. A greater and better knowledge and
      understanding of the aging process will allow to identify and select those old
      patients that can benefit from prevention and treatment options, and more
      importantly will identify those other patients that are not candidates to
      treatments with curative intention because of their frail status. Progress in
      surgery, mainly in minimally invasive surgery, and its application to the field
      of oncologic surgery allows to forecast that a greater number of aging patients
      will benefit from treatment with curative intent. Age will not be a barrier for
      adequate treatment in healthy elderly patients, especially in those with long
      life expectancy and functional reserves. Fighting this healthcare discrimination
      is one of the main priorities in the strategy of improved health in the elderly.
      We present in this study and analyze the foreseen changes in the world s
      population, particularly in Spain; the association between cancer and age with
      its peculiar specificities; the general criteria for frailty in older patients,
      the limitations that aging generate for adjuvant treatments, and the new
      alternatives of treatment to be used in elderly oncologic patients for the most
      frequent tumors.

PMID- 19159176
TI  - [Mediastinal mass in a cirrhotic patient].

PMID- 19159177
TI  - [Pedunculated hepatocellular carcinoma presenting as a mass in the right iliac
      fossa].

PMID- 19159178
TI  - [Recurrent acute liver toxicity from intravenous methylprednisolone].
AB  - Adverse drug reactions (hepatotoxicity) are a frequent cause of acute liver
      injury with a wide clinical and histological spectrum. An early recognition of
      drug-related liver disease has been considered essential in clinical practice due
      to potential risks. In most cases exposure discontinuation improves the clinical
      picture.Steroids are used in a variety of clinical settings. However, intravenous
      steroids have rarely been associated with hepatotoxicity. We report the case of a
      middle-aged woman with multiple sclerosis who received a bolus of
      methylprednisolone on three occasions for the management of relapsing disease,
      with the development of repeated episodes of elevated liver enzymes after
      corticoid administration. In the third episode a liver biopsy was performed,
      which showed acute hepatitis with bridging necrosis; such histological picture
      has not been described before in patients treated with intravenous steroids.

PMID- 19159179
TI  - [Primary hepatic lymphoma - favorable outcome with chemotherapy plus rituximab].
AB  - This article describes the case of a patient with a non-Hodgkin primary hepatic
      lymphoma who was successfully treated with chemotherapy combined with rituximab.
      Using the Medical Subject Headings the published reports of this rare entity were
      reviewed.

PMID- 19159180
TI  - [Pancreatic-pleural fistula secondary to pancreatic pseudocyst. A complication of
      uncertain outcome].

PMID- 19159181
TI  - Simultaneous failure of Pillcam Colon and Pillcam SB.

PMID- 19159182
TI  - [Acute hydatid pancreatitis].

PMID- 19159183
TI  - [The term "tumor marker" under revision. Report of a patient demonstrating such
      need (liver cirrhosis and CA 12.5)].

PMID- 19159184
TI  - [Appendicular mucocele].

PMID- 19159185
TI  - [Dysphagia lusoria].

PMID- 19159186
TI  - Selective growth of well-aligned semiconducting single-walled carbon nanotubes.
AB  - High-density arrays of perfectly aligned single-walled carbon nanotubes (SWNTs)
      consisting almost exclusively of semiconducting nanotubes were grown on ST-cut
      single crystal quartz substrates. Raman spectroscopy together with electrical
      measurements of field effect transistors (FETs) fabricated from the as-grown
      samples showed that over 95% of the nanotubes in the arrays are semiconducting.
      The mechanism of selective growth was explored. It is proposed that introducing
      methanol in the growth process, combined with the interaction between the SWNTs
      and the quartz lattice, leads to the selective growth of aligned semiconducting
      nanotubes. Such a high density of horizontally aligned semiconducting SWNTs can
      be readily used in high current nanoFETs and sensors. This method demonstrates
      great promise to solve one of the most difficult problems which limits
      application of carbon nanotubes in nanoelectronicsthe coexistence of metallic and
      semiconducting nanotubes in samples produced by most, if not all, growth methods.

PMID- 19159187
TI  - Indene-based scaffolds. 2. An indole-indene switch: discovery of novel
      indenylsulfonamides as 5-HT6 serotonin receptor agonists.
AB  - Scaffold selection involving an indole-to-indene core change led to the discovery
      of a series of indenylsulfonamides that act as 5-HT6 serotonin receptor agonists.
      The variety of the targeted ligands and their synthetic complexity required
      multistep synthetic approaches. The novel indenylsulfonamides exhibited variable
      binding affinities for the 5-HT6 receptor, and the in vitro primary binding
      profiles of the preferred compounds revealed them to be 5-HT6 receptor agonists
      with Ki values > or =4.5 nM. The structural changes responsible for enhancing the
      affinities indicated a directing effect modulated by the nature of the indene
      core, the substitution at the aminoethyl side chain, and especially by the
      aryl(heteroaryl)sulfonyl group on the indene 5-position. A representative of the
      family, the N-(inden-5-yl)imidazothiazole-5-sulfonamide (43), exhibited a high
      affinity and functioned as a potent full agonist for the 5-HT6 receptor (Ki = 4.5
      nM, EC50 = 0.9 nM, Emax = 98%).

PMID- 19159188
TI  - Silicon (100) electrodes resistant to oxidation in aqueous solutions: an
      unexpected benefit of surface acetylene moieties.
AB  - Here we report on the functionalization of alkyne-terminated alkyl monolayers on
      highly doped Si(100) using "click" reactions to immobilize ferrocene derivatives.
      The reaction of hydrogen-terminated silicon surfaces with a diyne species was
      shown to afford very robust functional surfaces where the oxidation of the
      underlying substrate was negligible. Detailed characterization using X-ray
      photoelectron spectroscopy, X-ray reflectometry, and cyclic voltammetry
      demonstrated that the surface acetylenes had reacted in moderate yield to give
      surfaces exposing ferrocene moieties. Upon extensive exposure of the redox-active
      architecture to oxidative environments during preparative and characterization
      steps, no evidence of SiOx contaminants was shown for derivatized SAMs prepared
      from single-component 1,8-nonadiyne, fully acetylenylated, monolayers. An
      analysis of the redox behavior of the prepared Si(100) electrodes based on
      relevant parameters such as peak splitting and position and shape of the
      reduction/oxidation waves depicted a well-behaved redox architecture whose
      spectroscopic and electrochemical properties were not significantly altered even
      after prolonged cycling in aqueous media between -100 and 800 mV versus Ag|AgCl.
      The reported strategy represents an experimentally simple approach for the
      preparation of silicon-based electrodes where, in addition to close-to-ideal
      redox behavior, remarkable electrode stability can be achieved. Both the presence
      of a distal alkyne moiety and temperatures of formation above 100 degrees C were
      required to achieve this surface stabilization.

PMID- 19159189
TI  - Monte Carlo simulation of surfactant adsorption on hydrophilic surfaces.
AB  - Monte Carlo simulations have been carried out to study the adsorption behavior of
      small flexible amphiphilic molecules on solid surfaces from aqueous solutions. A
      simple coarse-grained solvent-free off-lattice model, with a square-well pair
      potential and hard core excluded volume effect, has been used. Adsorption
      isotherms for weakly and strongly hydrophilic homogeneous surfaces have been
      determined. The adsorbed layer displays a coexistence region with an upper
      critical point. Below the critical temperature a densely packed patch coexists
      with a two-dimensional gas-analogous phase. Above the critical temperature, a
      percolating network forms at higher surfactant concentrations. Depending on the
      ratio between the strength of the hydrophobic effect and the adsorption energy, a
      large variety of associates has been observed. Monolayers, bilayers, admicelles,
      small clusters, and percolating networks as typical associate structures have
      been found. In the four-region model, which is extended by the coexistence
      region, a characteristic adsorbed layer structure for each region can be
      detected. Intermediate structure types have been produced by variation of the
      adsorption energy.

PMID- 19159190
TI  - Modeling adsorption processes of poly-p-phenylenevinylene precursor and sodium
      acid dodecylbenzenesulfonate onto layer-by-layer films using a Langmuir-type
      metastable equilibrium model.
AB  - The adsorption kinetics curves of poly(xylylidene tetrahydrothiophenium chloride)
      (PTHT), a poly-p-phenylenevinylene (PPV) precursor, and the sodium salt of
      dodecylbenzene sulfonic acid (DBS), onto (PTHT/DBS)n layer-by-layer (LBL) films
      were characterized by means of UV-vis spectroscopy. The amount of PTHT/DBS and
      PTHT adsorbed on each layer was shown to be practically independent of adsorption
      time. A Langmuir-type metastable equilibrium model was used to adjust the
      adsorption isotherms data and to estimate adsorption/desorption coefficients
      ratios, k=kads/kdes, values of 2x10(5) and 4x10(6) for PTHT and PTHT/DBS layers,
      respectively. The desorption coefficient has been estimated, using literature
      values for poly(o-methoxyaniline) desorption coefficient, as was found to be in
      the range of 10(-9) to 10(-6) s(-1), indicating that quasi equilibrium is rapidly
      attained.

PMID- 19159191
TI  - Relaxation times in single event electrospraying controlled by nozzle front
      surface modification.
AB  - Single event electrospraying (SEE) is a method for on-demand deposition of
      femtoliter to picoliter volumes of fluids. To determine the influence of the size
      of the meniscus on the characteristics of the single event electrospraying
      process, glass capillaries were used with and without an antiwetting coating
      comprising a self-assembled 1H,1H,2H,2H-perfluorodecyltrichlorosilane-based
      monolayer to control the meniscus size. A large difference was found in driving
      single event electrospraying from a small meniscus compared to what is needed to
      generate a single event electrospraying from a large meniscus. Furthermore, after
      studying the different time constants related to the electrical and the
      hydrodynamic phenomena, we are able to explain the timing limitations of the
      deposition process from both a small and a large meniscus. The hydrodynamic
      relaxation time is significantly reduced in the case of the modified capillary,
      and the timing of SEE, which determines the deposition time, is limited by the
      resistor-capacitor RC time of the electrical circuit needed to drive the SEE. We
      have built a model that describes the almost one-dimensional motion of the liquid
      in the capillary during pulsing. The model has been used to estimate the
      hydrodynamic relaxation times related to the meniscus-to-cone and cone-to
      meniscus transitions during SEE. By confining the meniscus to the inner diameter
      of the nozzle, we are able to deposit a volume smaller than 5 pL per SEE.

PMID- 19159192
TI  - Controlled step growth of molecularly linked gold nanoparticles: from metallic
      monomers to dimers to polymeric nanoparticle chains.
AB  - The solution-phase assembly of 15 nm gold particles into relatively linear chains
      of fairly controllable length of up to 1 mum is achieved by molecularly linking
      nanoparticles with alkanedithiols. This step-growth process can be controlled to
      prepare dimers, oligomers, and polymer-like gold nanoparticle chains by varying
      the ratio of alkanedithiols to nanoparticles. These size-controlled, relatively
      linear aggregates remain suspended in ethanol solution without precipitation for
      several weeks to months depending on the chain length. The resulting soluble
      nanoparticle assemblies were characterized by a variety of techniques including
      cryogenic transmission electron microscopy. The surface plasmon coupling of
      regularly spaced gold nanoparticles in these chains could be of interest in the
      fabrication of optical waveguide and nanoelectronic systems.

PMID- 19159193
TI  - Dynamic micromapping of CO2 sorption in coal.
AB  - We have applied X-ray and neutron small-angle scattering techniques (SAXS, SANS,
      and USANS) to study the interaction between fluids and porous media in the
      particular case of subcritical CO2 sorption in coal. These techniques are
      demonstrated to give unique, pore-size-specific insights into the kinetics of CO2
      sorption in a wide range of coal pores (nano to meso) and to provide data that
      may be used to determine the density of the sorbed CO2. We observed densification
      of the adsorbed CO2 by a factor up to five compared to the free fluid at the same
      (p, T) conditions. Our results indicate that details of CO2 sorption into coal
      pores differ greatly between different coals and depend on the amount of mineral
      matter dispersed in the coal matrix: a purely organic matrix absorbs more CO2 per
      unit volume than one containing mineral matter, but mineral matter markedly
      accelerates the sorption kinetics. Small pores are filled preferentially by the
      invading CO2 fluid and the apparent diffusion coefficients have been estimated to
      vary in the range from 5x10(-7) cm2/min to more than 10(-4) cm2/min, depending on
      the CO2 pressure and location on the sample.

PMID- 19159194
TI  - Biomimetic transannular oxa-conjugate addition approach to the 2,6-disubstituted
      dihydropyran of laulimalide yields an unprecedented transannular oxetane.
AB  - 2,6-Disubstituted dihydropyrans are a common feature in many bioactive
      polyketides, including the anticancer marine polyketide laulimalide. While much
      of the uncharacterized biosynthetic pathway for laulimalide can be confidently
      postulated, the biosynthetic origins of the trans 2,6-disubstituted dihydropyran
      cannot. We hypothesize that a transannular oxa-conjugate addition in a
      macrocyclic laulimalide precursor could be the origin of the 2,6-dihydropyran. To
      test this hypothesis, we constructed a model containing the key functional groups
      for oxa-conjugate addition-mediated dihydropyran formation. Under acid-mediated
      conditions, the model under went regiospecific oxa-conjugate addition producing a
      stable trans oxetane as the only regioisomer. The desired, more stable
      dihydropyran was not detected. This unprecedented regiospecificity is unexpected
      due to the ring strain of the oxetane and the anticipated facile ring opening
      retro-oxa-conjugate addition. The oxetane is stable to acid and basic conditions,
      as are a number of literature acyclic oxetanes that could undergo similar retro
      oxa-conjugate addition. While the source of the oxetane kinetic stability is yet
      to be characterized, it may enable general oxetane construction via oxa-conjugate
      addition. The more stable dihydropyran regioisomer could not be generated due to
      poor geometrical orbital alignment and hard-soft incompatibility between the hard
      oxygen nucleophile and the soft activated polyenoate electrophile. These factors
      disfavor the breaking of conjugation by oxa-conjugate addition. Based on these
      results we propose that dihydropyran formation does not occur on completed
      polyketide macrocycles as we had proposed but rather during polyketide
      biosynthesis on the growing polyketide chain.

PMID- 19159195
TI  - Helix-coil transition of DNA monitored by pressure perturbation calorimetry.
AB  - We report the first use of pressure perturbation calorimetry (PPC) to
      characterize the heat-induced helix-coil transition of DNA polymers. The
      alternating copolymer poly[d(A-T)] was studied in aqueous solutions containing
      5.2 and 18.2 mM Na+; it exhibited helix-coil transition temperatures of 33.6 and
      44.7 degrees C, respectively. The transition is accompanied by a negative molar
      volume change, DeltaV) -2.6 and -2.1 mL/mol (base pair), respectively, and an
      increase in the coefficient of thermal expansion, Deltaalpha=+5x10(-4) K(-1) (at
      both ionic strengths). These values are consistent with a greater hydration of
      the coil form. The larger water-accessible surface area of the coil causes more
      water molecules to assume a bound, more densely packed structure that then
      gradually decreases with increasing temperature, leading to a larger value of R.
      The magnitude of the volume changes detected by PPC were larger than those
      deduced from high-pressure UV spectroscopy, shedding light on the effect of
      pressure on DeltaV. The shape of the PPC peak was nearly identical to the shape
      of the DSC peak, providing direct evidence for the correlation between the molar
      volume change and enthalpy change for the helix to coil transition of DNA.

PMID- 19159196
TI  - A large enhancement of photoinduced second harmonic generation in CdI2--Cu
      layered nanocrystals.
AB  - Photoinduced second harmonic generation (PISHG) in undoped as well as in various
      Cu-doped (0.05-1.2% Cu) CdI2 nanocrystals was measured at liquid nitrogen
      temperature (LNT). It was found that the PISHG increases with increasing Cu
      doping up to approximately 0.6% and then decreases almost to that for the undoped
      CdI2 for doping higher than approximately 1%. The values of the second-order
      susceptibility ranged from 0.50 to 0.67 pm V(-1) for the Cu-doped nanocrystals
      with a thickness of 0.5 nm. The Cu-doping dependence shown in a parabolic fashion
      suggests a crucial role of the Cu agglomerates in the observed effects. The PISHG
      in crystals with various nanosizes was also measured at LNT. The size dependence
      demonstrated the quantum-confined effect with a maximum PISHG for 0.5 nm and with
      a clear increase in the PISHG with decreasing thickness of the nanocrystal. The
      Raman scattering spectra at different pumping powers were taken for thin
      nanocrystals, and the phonon modes originating from interlayer phonons were
      observed in the spectra. The results were discussed within a model of
      photoinduced electron-phonon anharmonicity.

PMID- 19159197
TI  - Phase diagram of P3HT/PCBM blends and its implication for the stability of
      morphology.
AB  - In this work, the phase diagram of poly(3-hexyl thiophene) (P3HT) and [6,6]
      phenyl C61-butyric acid methyl ester (PCBM) blends is measured by means of
      standard and modulated temperature differential scanning calorimetry. Blends were
      made by solvent-casting from chlorobenzene, as blends cast from toluene or 1,2
      dichlorobenzene prove to retain effects of phase segregation during casting,
      hindering the determination of the phase diagram. The film morphology of
      P3HT/PCBM blends cast from chlorobenzene results from a dual crystallization
      behavior, in which the crystallization of each component is hindered by the other
      component. A single glass transition is observed for all compositions. The glass
      transition temperature (Tg) increases with increasing concentration of PCBM: from
      12.1 degrees C for pure P3HT to 131.2 degrees C for pure PCBM. The observed Tg
      defines the operating window for the thermal annealing and explains the long-term
      instability of both the morphology and the photovoltaic performance of the
      P3HT/PCBM solar cells.

PMID- 19159198
TI  - Inclusion complex formation of ionic liquids and other cationic organic compounds
      with cucurbit[7]uril studied by 4',6-diamidino-2-phenylindole fluorescent probe.
AB  - The encapsulation of 4',6-diamidino-2-phenylindole (DAPI) in the cucurbit[7]uril
      (CB7) cavity was studied by absorption, fluorescence, and NMR spectroscopic
      methods in aqueous solution. The profound change in the fluorescence
      characteristics was attributed to the formation of a very stable 1:1 inclusion
      complex. Three independent methods provided (1.1+/-0.1)x10(7) M(-1) value for the
      binding constant. DAPI proved to be an excellent fluorescent probe for the
      investigation of the competitive binding of ionic liquids, surfactants, and
      biologically important compounds to CB7. The equilibrium constant of 1-alkyl-3
      methylimidazolium inclusion was found to go through a maximum as the aliphatic
      chain length was increased, reaching the highest value for the hexyl derivative.
      The variation of the anion had a small effect. Among cationic surfactants
      containing a dodecyl tail, the stability of CB7 complex diminished with the
      growing hydrophobicity of the head group.

PMID- 19159199
TI  - Hydrolytic degradation behavior of a renewable thermoplastic elastomer.
AB  - The hydrolytic degradation of polylactide-polymenthide-polylactide triblock
      copolymers (37 degrees C, pH 7.4) is compared to that of the component
      homopolymers. In addition to mass loss and water uptake measurements, size
      exclusion chromatography (SEC), 1H NMR spectroscopy, differential scanning
      calorimetry (DSC), and mechanical testing were used to monitor property changes
      during degradation. The rate of copolymer degradation was significantly
      influenced by the molecular weight of the polylactide end blocks. Mass loss of
      the polylactide homopolymer and the copolymer samples was observed once a
      decrease in the total molecular weight of the samples of 20% occurred. 1H NMR
      spectroscopy and DSC analysis of the copolymers during degradation revealed that
      the released oligomers contained mostly polylactide. After initial water uptake
      in which the mechanical properties were compromised to an extent, the Young's
      modulus and elongation at break of the biorenewable copolymers remained
      relatively unperturbed for up to 16 weeks, with significant retention of
      thermoplastic elastomeric properties for up to 21 weeks.

PMID- 19159201
TI  - Ab initio investigation of dissolution mechanisms in aluminosilicate minerals.
AB  - The reactions of aluminosilicate clusters with water are investigated using ab
      initio calculations. There are several reaction sites on a mineral surface, and,
      in the case of aluminosilicates, the dissolution chemistry is dictated by
      chemically distinct surface termination sites: Al and Si. Environmental factors
      such as pH determine the protonation state and configuration around these
      terminal sites. The dissolution mechanisms for Al- and Si-terminated sites in
      protonated, neutral, and deprotonated states are determined using density
      functional theory calculations. In all protonation states, Si are tetra
      coordinated; however, the ability of Al to exist in tetra-, penta-, and hexa
      coordination states makes the dissolution mechanisms for the two types of
      terminal sites fundamentally different. The calculated barrier heights for Al
      terminated sites are predicted to be lower than those for Si-terminated sites, a
      trend that has been observed in experimental studies. The sensitivity of the
      calculations on the choice of density functionals and basis sets is tested using
      three functionals: B3LYP, PBE1PBE, and M05-2X, in combination with the 6
      311+G(d,p) and MG3S basis sets. For all these calculations, the geometries of the
      stationary points along the reaction path and the barrier heights are presented.

PMID- 19159200
TI  - Polygalactose containing nanocages: the RAFT process for the synthesis of hollow
      sugar balls.
AB  - Hollow poly(6-O-acryloyl-alpha-D-galactopyranose) (PAGP) nanospheres were
      prepared in a facile manner using the RAFT (reversible addition fragmentation
      chain transfer) process. Initially, an amphiphilic block copolymer, poly(lactide)
      block-poly(6-O-acryloyl-alpha-D-galactopyranose) (PLA-b-PAGP), was synthesized
      using a poly(lactide) (PLA) macroRAFT agent. It was attained in high yields and
      displayed low PDI values. The block copolymers self-assembled in aqueous solution
      to form micelles with pendent galactose moieties covering the surface. By using
      hexandiol diacrylate the micelles were cross-linked at the nexus of the
      copolymer, creating stable aggregates. Aminolysis with hexylamine allowed the
      removal of the PLA core without any detrimental effect on the glycopolymer units
      to produce hollow nanocages. Characterization of these hollow "sugar balls" with
      transmission electron microscopy (TEM) showed the cross-linked micelles with a
      central void due to the removal of the hydrophobic block. These micelles are
      advantageous in drug delivery applications, especially those involving the liver,
      thanks to the pendent galactose functionalities covering the surfaces of the
      nanocages.

PMID- 19159202
TI  - Dynamics of Si-H-Si bridges in agostically stabilized silylium ions.
AB  - The silylium ion [C(6)(SiMe(2))(SiHMe(2))(5)](+) offers an amazing example of
      multiple Si...H interactions. It exhibits a symmetric Si(alpha)-H-Si(alpha) motif
      supported by two additional Si(beta)-H...Si(alpha) agostic interactions. This
      cation is highly fluctional in NMR spectra at room temperature due to shift of
      the hydride bridge. The DFT calculations show that the hydride shift is related
      to internal rotation of silyl groups. We performed NMR, static DFT, and dynamics
      studies of this process and found two possible mechanisms, associated with
      internal rotation of either beta- or gamma-silyls. The energy barrier is largely
      caused by the silyl internal rotation, whereas the hydride transfer itself is
      intrinsically quite easy. The gamma-silyl rotation is somewhat more favorable
      than the beta-silyl rotation. Vibrational dynamics of the cation is also
      discussed.

PMID- 19159203
TI  - Excited-state dynamics of [(1,1'-biphenyl)-4,4-diyldi-2,1
      ethenediyl]bis(dimethylsilane).
AB  - The relaxation dynamics of excited electronic states of [(1,1'-biphenyl)-4,4'
      diyldi-2,1-ethenediyl]bis(dimethylsilane) dissolved in various solvents with
      varied polarity and viscosity have been investigated. Upon excitation at
      wavelength 266 nm, we measured the fluorescence curves that exhibit a rise time
      constant approximately 100 fs, and two decay time constants, 7-65 ps and
      approximately 1 ns. We attribute the former decay to upper excited states to the
      S(1) state, and the latter decay to geometric relaxation and the lifetime of the
      S(1) state. Only the tens of picosecond decay shows a dependence on the solvent
      viscosity, indicating that the torsional motion dominates the relaxation.
      Theoretical calculations were performed to obtain the optimized structures of the
      free [(1,1'-biphenyl)-4,4'-diyldi-2,1-ethenediyl]bis(dimethylsilane) molecule in
      its ground and first excited states with methods B3LYP/6-311G(d) and CIS/6
      311G(d), respectively. The results of these calculations show that the dihedral
      angle between the two phenyl rings is approximately 34 degrees for trans and
      approximately 38 degrees for cis conformers in the ground state and that the
      first excited state has a planar structure, in agreement with the experimental
      results that indicate that the torsional motion of two phenyl groups elevates the
      relaxation of the S(1) state. Enhanced vibrational relaxation of S(1) in
      alcoholic solvents is observed. Rapid relaxation in methanol-OH compared with
      that in methanol-OD is explained by the excess energy dissipated efficiently
      through high-frequency vibrational mode (>500 cm(-1)).

PMID- 19159204
TI  - Carbon nanoparticle-enhanced immunoelectrochemical detection for protein tumor
      marker with cadmium sulfide biotracers.
AB  - We have developed a sensitive electrochemical immunoassay system for the
      detection of a protein tumor marker, carcinoembryonic antigen (CEA), that is
      based on a carbon nanoparticle (CNP)/poly(ethylene imine) (PEI)-modified screen
      printed graphite electrode (CNP-PEI/SPGE) covered with anti-CEA antibodies. The
      signal amplification strategy--using CdS nanocrystals as biotracers and CNPs to
      enhance electron transfer--improves the sensitivity and detection limit for CEA,
      suggesting that this system holds promise for development into a point-of-care or
      disposable home-care self-diagnostic tool. This biosensor is based on a sandwich
      complex immunoassay, which we assembled from sequential layers of the anti-CEA
      antibody (alphaCEA) on CNP-PEI/SPGE, the CEA sample, and the CdS nanocrystal
      quantum dots (QDs) sensitized with alphaCEA (alphaCEA-CdS QD). We used square
      wave anodic stripping voltammetry (SWASV) to amplify the signal current response
      obtained from the dissolved alphaCEA-CdS QDs. The calibration curve for CEA
      concentration was linear in the range of 0.032-10 ng/mL; the detection limit
      (estimated as the mean of the blank sample plus three times the standard
      deviation obtained on the blank sample) was 32 pg/mL (equivalent to 160 fg in a 5
      microL sample). This method is suitably precise and sensitive to function as a
      means of determining urinary CEA, which is a better marker than serum CEA for the
      early detection of urothelial carcinoma.

PMID- 19159205
TI  - Post-CCSD(T) ab initio thermochemistry of halogen oxides and related hydrides
      XOX, XOOX, HOX, XOn, and HXOn (X = F, Cl), and evaluation of DFT methods for
      these systems.
AB  - Benchmark-quality W4 (and related) thermochemical data were obtained for the
      fluorine and chlorine oxides and some related hydrides, all of which are of
      interest for computational modeling of atmospheric processes. Our best available
      estimates for total atomization energies at 0 K are the following: HO2 165.97 +/-
      0.14, H2O2 252.08 +/- 0.14, HOF 149.24 +/- 0.14, FO 51.17 +/- 0.10, F2O 89.43 +/-
      0.14, FO2 130.15 +/- 0.16, F2O2 146.00 +/- 0.16, ClO 63.40 +/- 0.10, HOCl 156.73
      +/- 0.14, Cl2O 96.93 +/- 0.16, OClO 122.33 +/- 0.16, ClOO 121.88 +/- 0.32, Cl2O2
      142.9 +/- 0.3, ClO3 159.9 +/- 0.4, HClO2 192.0 +/- 0.4, HClO3 258.1 +/- 0.3, and
      HClO4 313.4 +/- 1 kcal/mol. For several of these species, the total atomization
      energy contains unusually large components from correlation effects beyond
      CCSD(T). The geometry of FOOF is significantly affected by connected quadruple
      excitations. A large variety of DFT exchange-correlation functionals have been
      evaluated for these systems and observations on their performance are offered.
      Our best available estimates for deltaHf,0o are the following: HO2 3.65 +/- 0.14,
      H2O2 -30.82 +/- 0.14, HOF -20.15 +/- 0.14, FO 26.28 +/- 0.11, F2O 6.48 +/- 0.14,
      FO2 6.30 +/- 0.16, F2O2 8.90 +/- 0.18, ClO 24.19 +/- 0.10, HOCl -17.51 +/- 0.14,
      Cl2O 19.24 +/- 0.16, OClO 24.26 +/- 0.16, ClOO 24.69 +/- 0.16, Cl2O2 32.3 +/-
      0.3, ClO3 45.7 +/- 0.4, HClO2 6.2 +/- 0.4, HClO3 -0.9 +/- 0.3, and HClO4 2.9 +/-
      1.0 kcal/mol. (The corresponding values at 298.15 K are 2.96 +/- 0.14, -32.24 +/-
      0.14, -20.84 +/- 0.14, 26.43 +/- 0.11, 5.94 +/- 0.14, 5.87 +/- 0.16, 7.84 +/-
      0.18, 24.18 +/- 0.10, -18.20 +/- 0.14, 18.82 +/- 0.16, 23.67 +/- 0.16, 24.30 +/-
      0.16, 31.5 +/- 0.3, 44.3 +/- 0.4, 5.0 +/- 0.4, -2.6 +/- 0.3, and -0.1 +/- 1.0
      kcal/mol, respectively.)

PMID- 19159206
TI  - Aqueous solution of UCl6(2-) in O2 saturated acidic medium: an efficient system
      to scavenge all primary radicals in spurs produced by irradiation.
AB  - Absorbance measurements find the yield of the oxidation of U(IV) to be (8.75 +/-
      0.05) x 10(-7) mol J(-1) in the (60)Co gamma radiolysis of aqueous solutions
      containing 4.4 x 10(-3) mol L(-1) U(IV) in the presence of O(2) saturated 2 mol
      L(-1) Cl(-) at pH = 0. This high value of oxidation yield suggests that all
      primary radicals formed by water decomposition are scavenged in these solutions.
      Simulations using a nonhomogeneous stochastic kinetic track model agree with the
      experimental results and are used to explain the mechanism for scavenging
      radicals and oxidation of U(IV).

PMID- 19159207
TI  - Oscillations and mechanistic analysis of the chlorite-sulfide reaction in a
      continuous-flow stirred tank reactor.
AB  - Sustained oscillations in pH and redox potential are found in the chlorite
      sulfide reaction in a continuous-flow stirred tank reactor (CSTR). Autocatalytic
      oxidation of HSO(3)(-) by ClO(2)(-) is the major source of positive feedback of
      hydrogen ions. The reaction between H(2)S and ClO(2)(-) to form S(8), which
      consumes H(+), is an important source of negative feedback. A model consisting of
      five protonation-deprotonation equilibria and nine redox reactions is proposed
      for the oscillatory reaction between S(2-) and ClO(2)(-). The 10 species included
      are HS(-), H(2)S, S(2)O(3)(2-), SO(3)(2-), HSO(3)(-), OCl(-), HOCl, ClO(2)(-),
      H(+), and OH(-). In contrast to the H(2)O(2)-S(2-) oscillatory reaction,
      S(2)O(3)(2-) is shown here by capillary electrophoresis to be an important
      intermediate. Simulations give qualitative agreement with the pH oscillatory
      behavior observed in the CSTR.

PMID- 19159208
TI  - Nuclear magnetic resonance and electron paramagnetic resonance as analytical
      tools to investigate structural features of archaeological leathers.
AB  - Archaeological waterlogged leathers dated from the 13th to 17th century have been
      analyzed using carbon-13 high-resolution solid-state nuclear magnetic resonance
      (NMR) and electron paramagnetic resonance (EPR). The NMR and EPR spectra have
      been compared to modern vegetable-tanned leathers and crude hide. Both techniques
      allowed us to fully characterize the samples and better understand the changes
      occurring during aging in water environment. The main features of the
      archaeological leathers are the high contents in iron and the absence of residual
      vegetable tannins. Traces of lubricants could not be detected either. The
      accumulation of iron oxides may have played a role in the conservation of the
      archaeological objects and explain the surprising good conservation state of the
      leather samples as was observed in the NMR spectra. The absence of tannins and
      lubricants in the studied archaeological samples is also discussed. It may be a
      consequence of aging in water-rich environment. The analysis strategy described
      in this paper can be systematically applied to characterize archaeological or
      historical leather samples.

PMID- 19159209
TI  - Rotational Dynamics of Strongly Adsorbed Solute at the Water Surface.
AB  - The orientational dynamics of nitrobenzene adsorbed at the water liquid/vapor
      interface as a model for the orientational dynamics of surface-active solute are
      studied using classical molecular dynamics computer simulations. By varying the
      charge distribution of the solute and by comparing the results with those in bulk
      water, we are able to determine the effects of dielectric and mechanical
      frictions on reorientation dynamics and to correlate the orientational dynamics
      with the specific hydration of the solute. As in our previous model studies, we
      find that the equilibrium orientational relaxation is much slower in the bulk
      than at the interface. Variations of the solute charge distributions show that,
      as the solute becomes more polar, the surface rotation slows and approaches the
      bulk behavior. The reorientation dynamics are quite anisotropic, with out-of
      plane rotation faster than in-plane rotation. This anisotropy disappears when the
      solute-water electrostatic interactions are turned off.

PMID- 19159211
TI  - A crossed molecular beam study of the phenyl radical reaction with 1,3-butadiene
      and its deuterated isotopologues.
AB  - The reactions between the phenyl radical (C(6)H(5)) and 1,3-butadiene
      (CH(2)CHCHCH(2)) together with its D6- and D4-isotopologues were studied under
      single collision conditions. The scattering data suggest that the reaction
      proceeds via indirect scattering dynamics and is initiated by an addition of the
      phenyl radical to the terminal carbon atom of the 1,3-butadiene molecule to form
      a C(6)H(5)CH(2)CHCHCH(2) intermediate. Then, the collision complex undergoes a
      hydrogen atom loss through a tight exit transition state to form the 1-phenyl-1,3
      butadiene product. Reactions with isotopically labeled reactants verify
      experimentally that the hydrogen loss originates from the terminal carbon atom of
      the 1,3-butadiene reactant. Our results are also compared with other phenyl
      radical reactions with unsaturated hydrocarbons studied earlier in our
      laboratory.

PMID- 19159212
TI  - Detection of intact ricin in crude and purified extracts from castor beans using
      matrix-assisted laser desorption ionization mass spectrometry.
AB  - Ricin is a highly toxic protein from the seeds of the castor bean plant. Crude
      extracts from castor beans are toxic by several routes, and there is
      international concern about the use of these extracts by terrorist organizations.
      Lethality in aerosolized form has spurred the development of methods for the
      rapid detection of this protein from air samples that is critical in determining
      the illicit use of this material. Matrix-assisted laser desorption ionization
      (MALDI) mass measurement with an automated laser firing sequence was used to
      detect intact ricin from solutions containing less than 4 microg/mL of ricin in
      the presence of other endogenous seed proteins. This sensitivity was attained
      with the addition of 0.01% Tween 80 to the extracts that greatly enhanced the
      ricin signal. Importantly, this treatment substantially reduces the interference
      from the castor bean seed storage proteins. Commonly the ricin signal can be
      completely obscured by the oligomers of seed storage proteins, and this treatment
      reveals the ricin molecular ion, allowing the analyst to make a judgment as to
      the ricin content of the extract. This method provides for sensitive and rapid
      identification of intact ricin from aqueous samples with little sample
      preparation and is amenable to automatic acquisition.

PMID- 19159213
TI  - A quantitative peptidomic analysis of peptides related to the endogenous opioid
      and tachykinin systems in nucleus accumbens of rats following naloxone
      precipitated morphine withdrawal.
AB  - We have applied a recently developed label-free mass spectrometry based
      peptidomic approach to identify and quantify a variety of endogenous peptides
      from rat nucleus accumbens following withdrawal in naloxone-precipitated,
      morphine-dependent rats of two separate strains. We focused on maturated,
      partially processed and truncated peptides derived from the peptide precursors
      proenkephalin, prodynorphin and preprotachykinin. The expression of several
      identified peptides was dependent on strain and was affected during morphine
      withdrawal.

PMID- 19159214
TI  - Real-time monitoring of hazardous air pollutants.
AB  - Selected ion flow tube mass spectrometry (SIFT-MS) is a technique that offers
      real-time alternatives to existing methods for monitoring hazardous air
      pollutants (HAPs) in the environment using chemical ionization. The use of this
      technique requires knowledge of the kinetic parameters of the reagent ions
      H(3)O(+), NO(+), and O(2)(+) that are most commonly used. We report here
      measurements with these reagent ions of kinetic parameters for 17 HAP molecules
      ranging from 1,1-dichloroethene to nitrobenzene. From these data, limits of
      quantitation are established for all 17 compounds on a commercial SIFT-MS
      instrument and are found to be well below the time-weighted averages required by
      legislating bodies for workplace conditions.

PMID- 19159215
TI  - Quantitative matrix-assisted laser desorption ionization-fourier transform ion
      cyclotron resonance (MALDI-FT-ICR) peptide profiling and identification of
      multiple-sclerosis-related proteins.
AB  - We introduce a matrix-assisted laser desorption ionization-Fourier transform ion
      cyclotron resonance (MALDI-FT-ICR) method for quantitative peptide profiling,
      using peak height as a measure for abundance. Relative standard deviations in
      peak height of peptides spiked over 3 orders of magnitude in concentration were
      below 10% and allowed for accurate comparisons between multiple sclerosis and
      controls. Application on a set of 163 cerebrospinal fluid (CSF) samples showed
      significantly differential abundant peptides, which were subsequently identified
      into proteins (e.g., chromogranin A, clusterin, and complement C3).

PMID- 19159216
TI  - Enhancement by Copper(II) of the voltammetric signal of vitamin B2 applied to its
      determination in breakfast cereals.
AB  - Addition of copper(II) to breakfast cereal samples was shown to significantly
      enhance the analytical signal obtained by electrochemical reduction of vitamin
      B(2) using linear sweep voltammetry on disposable carbon electrodes. The
      enhancement was observed only when dissolved oxygen was present. In model
      solutions the analytical signal was linear in the concentration range 6-150 ng/mL
      with a calculated limit of detection of 5 ng/mL (S/N = 3). This compared
      favorably with earlier work using a similar measurement approach--but in the
      absence of copper--in which the limit of detection was calculated to be 900
      ng/mL. The effects of potential interferents commonly found in cereals were
      examined. In addition to signal attenuation by both sugar and starch (already
      reported), folic acid was found to increase (+6%) and iron to decrease (-11%) the
      analytical signal when present in the maximum concentration ratios, with respect
      to vitamin B(2), that are normally found in breakfast cereals. Nevertheless, the
      simplicity of the approach was potentially attractive for near-line quality
      control applications in manufacturing. The utility of the measurement approach
      was demonstrated by the addition of excess copper(II) sulfate to determine
      vitamin B(2) in aqueous extracts of breakfast cereals. The results agreed well
      with those provided by the cereal manufacturer who used an established HPLC
      method.

PMID- 19159217
TI  - Identification of an Alkylhydroquinone from Rhus succedanea as an Inhibitor of
      Tyrosinase and Melanogenesis.
AB  - The alkylhydroquinone 10'(Z)-heptadecenylhydroquinone [HQ17(1)], isolated from
      the sap of the lacquer tree Rhus succedanea, was found to inhibit the activity of
      tyrosinase and to suppress melanin production in animal cells. The IC50 of
      HQ17(1) as a tyrosinase inhibitor was 37 microM versus 70 microM for hydroquinone
      (HQ), a known inhibitor of tyrosinase and melanogenesis. For the inhibition of
      melanin production in mouse B16 melanoma cells, the EC50 of HQ17(1) was 40 microM
      versus 124 microM for HQ. HQ17(1) induced much less oxidative stress than did HQ.
      The effectiveness in inhibiting melanin production could be mimicked by
      intermittent exposure of cells to HQ17(1). The potent inhibitory effects of
      HQ17(1) on tyrosinase activity and melanin production are likely due to its
      heptadecenyl chain, which facilitates retention of the compound in cell membrane
      compartments and may impede oxidation of the hydroquinone ring. As tyrosinase
      activity accounts for postharvest browning of botanical products and animal skin
      melanogenesis, HQ17(1) could be useful for the preservation of these products or
      as a skin-whitening cosmetic.

PMID- 19159218
TI  - Glycoproteomics analysis of human liver tissue by combination of multiple enzyme
      digestion and hydrazide chemistry.
AB  - The study of protein glycosylation has lagged far behind the progress of current
      proteomics because of the enormous complexity, wide dynamic range distribution
      and low stoichiometric modification of glycoprotein. Solid phase extraction of
      tryptic N-glycopeptides by hydrazide chemistry is becoming a popular protocol for
      the analysis of N-glycoproteome. However, in silico digestion of proteins in
      human proteome database by trypsin indicates that a significant percentage of
      tryptic N-glycopeptides is not in the preferred detection mass range of shotgun
      proteomics approach, that is, from 800 to 3500 Da. And the quite big size of
      glycan groups may block trypsin to access the K, R residues near N-glycosites for
      digestion, which will result in generation of big glycopeptides. Thus many N
      glycosites could not be localized if only trypsin was used to digest proteins.
      Herein, we describe a comprehensive way to analyze the N-glycoproteome of human
      liver tissue by combination of hydrazide chemistry method and multiple enzyme
      digestion. The lysate of human liver tissue was digested with three proteases,
      that is, trypsin, pepsin and thermolysin, with different specificities,
      separately. Use of trypsin alone resulted in identification of 622 N-glycosites,
      while using pepsin and thermolysin resulted in identification of 317 additional N
      glycosites. Among the 317 additional N-glycosites, 98 (30.9%) could not be
      identified by trypsin in theory because the corresponding in silico tryptic
      peptides are either too small or too big to detect in mass spectrometer. This
      study clearly demonstrated that the coverage of N-glycosites could be
      significantly increased due to the adoption of multiple enzyme digestion. A total
      number of 939 N-glycosites were identified confidently, covering 523 noredundant
      glycoproteins from human liver tissue, which leads to the establishment of the
      largest data set of glycoproteome from human liver up to now.

PMID- 19159220
TI  - Profile hidden Markov models for analyzing similarities and dissimilarities in
      the bacterial reaction center and photosystem II.
AB  - The bacterial photosynthetic reaction center is the evolutionary ancestor of the
      Photosystem II reaction center. These proteins share the same fold and perform
      the same biological function. Nevertheless, the details of their molecular
      reaction mechanism differ. It is of significant biological and biochemical
      interest to determine which functional characteristics are conserved at the level
      of the protein sequences. Since the level of sequence identity between the
      bacterial photosynthetic reaction center and Photosystem II is low, a progressive
      multiple-sequence alignment leads to errors in identifying the conserved
      residues. In such a situation, profile hidden Markov models (pHMM) can be used to
      obtain reliable multiple-sequence alignments. We therefore constructed the pHMM
      with the help of a sequence alignment based on a structural superposition of both
      proteins. To validate the multiple-sequence alignments obtained with the pHMM,
      the conservation of residues with known functional importance was examined.
      Having confirmed the correctness of the multiple-sequence alignments, we analyzed
      the conservation of residues involved in hydrogen bonding and redox potential
      tuning of the cofactors. Our analysis reveals similarities and dissimilarities
      between the bacterial photosynthetic reaction center and Photosystem II at the
      protein sequence level, hinting at different charge separation and charge
      transfer mechanisms. The conservation analysis that we perform in this paper can
      be considered as a model for analyzing the conservation in proteins with a low
      level of sequence identity.

PMID- 19159221
TI  - Disposable nucleic acid biosensors based on gold nanoparticle probes and lateral
      flow strip.
AB  - In this article, we describe a disposable nucleic acid biosensor (DNAB) for low
      cost and sensitive detection of nucleic acid samples in 15 min. Combining the
      unique optical properties of gold nanoparticles (Au-NP) and the high efficiency
      of chromatographic separation, sandwich-type DNA hybridization reactions were
      realized on the lateral flow strips, which avoid multiple incubation, separation,
      and washing steps in the conventional nucleic acid biosensors. The captured Au-NP
      probes on the test zone and control zone of the biosensor produced the
      characteristic red bands, enabling visual detection of nucleic acid samples
      without instrumentation. The quantitative detection was performed by reading the
      intensities of the produced red bands with a portable strip reader. The
      parameters (e.g., the concentration of reporter probe, the size of Au-NP, the
      amount of Au-NP-DNA probe, lateral flow membranes, and the concentration of
      running buffer) that govern the sensitivity and reproducibility of the sensor
      were optimized. The response of the optimized device is highly linear over the
      range of 1-100 nM target DNA, and the limit of detection is estimated to be 0.5
      nM in association with a 15 min assay time. The sensitivity of the biosensor was
      further enhanced by using horseradish peroxidase (HRP)-Au-NP dual labels which
      ensure a quite low detection limit of 50 pM. The DNAB has been applied for the
      detection of human genomic DNA directly with a detection limit of 2.5 microg/mL
      (1.25 fM) by adopting well-designed DNA probes. The new nucleic acid biosensor
      thus provides a rapid, sensitive, low cost, and quantitative tool for the
      detection of nucleic acid samples. It shows great promise for in-field and point
      of-care diagnosis of genetic diseases and detection of infectious agents or
      warning against biowarfare agents.

PMID- 19159222
TI  - Redox-responsive recombination of carbon-carbon bonds on flexible tetrairon
      cores.
AB  - When a brown powder of 2a was dissolved in acetonitrile, 2a was converted to 2b.
      Equilibrium was reached at a 74:26 molar ratio within 1 week at 303 K. The
      isomerization proceeds through a cubane-like transition state, in which
      recombination of a carbon-carbon bond occurs.

PMID- 19159223
TI  - "Twin copper source" growth of metal-organic framework membrane: Cu(3)(BTC)(2)
      with high permeability and selectivity for recycling H(2).
AB  - In this communication, the copper net supported Cu(3)(BTC)(2) membranes have been
      successfully synthesized by means of a "twin copper source" technique. Separation
      studies on gaseous mixtures (H(2)/CO(2), H(2)/CH(4), and H(2)/N(2)) using the
      membrane revealed that the membrane possesses high permeability and selectivity
      for H(2) over CO(2), N(2), and CH(4). Compared with the conventional zeolite
      membranes, the copper net supported Cu(3)(BTC)(2) membrane exhibited high
      permeation flux in gas separation. Such highly efficient copper net supported
      Cu(3)(BTC)(2) membranes could be used to separate, recycle, and reuse H(2)
      exhausted from steam reforming natural gas.

PMID- 19159225
TI  - Switching the morphologies of cylindrical polycation brushes by ionic and
      supramolecular inclusion complexes.
AB  - Cylindrical polycation brushes form an ionic complex with surfactant sodium
      dodecyl sulfate (SDS) in aqueous solution, which causes a worm-to-sphere collapse
      of the brush. Alpha- and beta-cyclodextrin (CD) returns the brush to the worm
      like conformation by forming a supramolecular inclusion complex with SDS. When
      beta-CD was employed for the inclusion complex, addition of 1-adamantylammonium
      chloride releases SDS by forming a stronger inclusion complex, causing the
      recollapse of the brush to spheres.

PMID- 19159224
TI  - Light-operated mechanized nanoparticles.
AB  - Mesoporous silica (MCM-41) nanoparticles modified by azobenzene derivatives,
      capable of storing small molecules and releasing them following light
      irradiation, have been fabricated and characterized. In the presence of the beta
      cyclodextrin and/or pyrene-modified beta-cyclodextrin rings, the beta
      cyclodextrin and/or pyrene-modified beta-cyclodextrin rings will thread onto the
      azobenzene-containing stalks and bind to trans-azobenzene units to form the
      pseudorotaxanes, thus sealing the nanopores and stopping release of the cargo.
      Upon irradiation, the isomerization of trans-to-cis azobenzene units leads to the
      dissociation of the beta-cyclodextrin and/or pyrene-modified beta-cyclodextrin
      rings from the stalks, thus opening the gates to the nanopores and releasing the
      cargo.

PMID- 19159226
TI  - Fluorescence lifetime of actin in the familial hypertrophic cardiomyopathy
      transgenic heart.
AB  - Clinical studies have revealed that the D166V mutation in the ventricular myosin
      regulatory light chain (RLC) can cause a malignant phenotype of familial
      hypertrophic cardiomyopathy (FHC). It has been proposed that RLC induced FHC in
      the heart originates at the level of the myosin cross-bridge due to alterations
      in the rates of cross-bridge cycling. In this report, we examine whether the
      environment of an active cross-bridge in cardiac myofibrils from transgenic (Tg)
      mice is altered by the D166V mutation in RLC. The cross-bridge environment was
      monitored by tracking the fluorescence lifetime (tau) of Alexa488-phalloidin
      labeled actin. The fluorescence lifetime is the average rate of decay of a
      fluorescent species from the excited state, which strongly depends on various
      environmental factors. We observed that the lifetime was high when cross-bridges
      were bound to actin and low when they were dissociated from it. The lifetime was
      measured every 50 ms from the center half of the I-band during 60 s of rigor,
      relaxation and contraction of muscle. We found no differences between lifetimes
      of Tg-WT and Tg-D166V muscle during rigor, relaxation and contraction. The duty
      ratio expressed as a fraction of time that cross-bridges spend attached to the
      thin filaments during isometric contraction was similar in Tg-WT and Tg-D166V
      muscles. Since independent measurements showed a large decrease in the cross
      bridge turnover rate in Tg-D166V muscle compared to Tg-WT, the fact that the duty
      cycle remains constant suggests that the D166V mutation of RLC causes a decrease
      in the rate of cross-bridge attachment to actin.

PMID- 19159227
TI  - Ultrasound-induced switching of sheetlike coordination polymer microparticles to
      nanofibers capable of gelating solvents.
AB  - We herein demonstrate a new gelation mechanism based on a readily available
      coordination polymer {Zn(bibp)(2)(OSO(2)CF(3))(2)}(n), in which ultrasound
      changes the morphology of the material from sheetlike microparticles into
      nanofibers, resulting in the immobilization of organic solvents.

PMID- 19159228
TI  - Time-resolved EPR characterization of a folded conformation of photoinduced
      charge-separated state in porphyrin-fullerene dyad bridged by diphenyldisilane.
AB  - For development of the molecular solar-energy conversion systems, it is crucial
      to investigate how both the molecular geometry and electronic structure of
      electron donor-bridge-acceptor (D-B-A) molecules contribute to the electronic
      coupling for the charge-separation (CS) and charge-recombination (CR) processes.
      In a D-B-A system of a porphyrin-fullerene dyad (ZnP-C(60)) bridged by a
      diphenyldisilane spacer, we have characterized one specific folded molecular
      conformation in the CS state among several existing conformations using the time
      resolved electron paramagnetic resonance (TREPR) method at low temperature. To
      determine the molecular conformation and spin-spin exchange coupling of the CS
      state, we have considered (1) the electron spin polarization transfer from the
      excited triplet state of the C(60) moiety to the CS state and (2) the sublevel
      selective spin relaxations and CR in the CS state. In the CS state of this
      conformation, although the ZnP cation and C(60) anion radicals are in close
      proximity, direct overlap between their singly occupied molecular orbitals is
      small, resulting in detection of the long-lived CS state which has a totally
      different conformation from the optically detected, charge-transfer (CT) complex.
      It has been demonstrated that, among several folded and extended molecular
      conformations created by the flexibility of the -Si-Si- bridge, the EPR
      conformation can play a role on the prevention of the energy-wasting CR.

PMID- 19159230
TI  - Use of a renewable and degradable monomer to study the temperature-dependent
      olefin isomerization during ADMET polymerizations.
AB  - A detailed study of temperature, catalyst, and polymerization condition dependent
      isomerization side reactions occurring during ADMET polymerizations revealed
      important parameters for the design of defined polymers via this technique.

PMID- 19159229
TI  - Extending thymidine kinase activity to the catalytic repertoire of human
      deoxycytidine kinase.
AB  - Salvage of nucleosides in the cytosol of human cells is carried out by
      deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1). Whereas TK1 is only
      responsible for thymidine phosphorylation, dCK is capable of converting dC, dA,
      and dG into their monophosphate forms. Using structural data on dCK, we predicted
      that select mutations at the active site would, in addition to making the enzyme
      faster, expand the catalytic repertoire of dCK to include thymidine.
      Specifically, we hypothesized that steric repulsion between the methyl group of
      the thymine base and Arg104 is the main factor preventing the phosphorylation of
      thymidine by wild-type dCK. Here we present kinetic data on several dCK variants
      where Arg104 has been replaced by select residues, all performed in combination
      with the mutation of Asp133 to an alanine. We show that several hydrophobic
      residues at position 104 endow dCK with thymidine kinase activity. Depending on
      the exact nature of the mutations, the enzyme's substrate preference is modified.
      The R104M-D133A double mutant is a pyrimidine-specific enzyme due to large K(m)
      values with purines. The crystal structure of the double mutant R104M-D133A in
      complex with the L-form of thymidine supplies a structural explanation for the
      ability of this variant to phosphorylate thymidine and thymidine analogs. The
      replacement of Arg104 by a smaller residue allows L-dT to bind deeper into the
      active site, making space for the C5-methyl group of the thymine base. The unique
      catalytic properties of several of the mutants make them good candidates for
      suicide-gene/protein-therapy applications.

PMID- 19159231
TI  - High-efficiency preparation of macrocyclic diblock copolymers via selective click
      reaction in micellar media.
AB  - We report a novel strategy for the high-efficiency preparation of macrocyclic
      diblock copolymers at relatively high concentrations via the combination of
      supramolecular self-assembly and "selective" click reactions, relying on the fine
      control of spatial accessibility between terminal reactive groups. The linear
      precursor, alpha-alkynyl-omega-azido heterodifunctional poly(2-(2
      methoxyethoxy)ethyl methacrylate)-b-poly(oligo(ethylene glycol) methyl ether
      methacrylate), linear-PMEO(2)MA-b-POEGMA-N(3), self-assembles into micelles with
      PMEO(2)MA cores and POEGMA coronas at elevated temperatures. The spatial
      separation between reactive alkynyl and azide groups precludes click reactions
      within micelle entities. On the other hand, due to the unimer-micelle exchange
      equilibrium and the fact that unimer concentration is typically low (critical
      micellization concentration, CMC), click reactions occur exclusively for unimers.
      This eventually led to complete intramolecular cyclization of all linear
      precursors.

PMID- 19159232
TI  - Formation of self-assembled polyelectrolyte multilayer nanodots by scanning probe
      microscopy.
AB  - We demonstrate that patterned nanodots can be obtained from alternatively self
      assembled polyelectrolytes which consist of poly(acrylic acid) (PAA) and
      poly(allylamine hydrochloride) (PAH) by using atomic force microscopy. The
      surface potentials are easily reversible as positive or negative depending on the
      kind of the top polyelectrolyte layer. With the layer by layer growth, the
      nanodots are formed exactly on the charged area and their thicknesses
      proportionally increase to the total number of monolayers with a uniform
      thickness of about 0.5 nm.

PMID- 19159233
TI  - High-temperature nanoporous ceramic monolith prepared from a polymeric
      bicontinuous microemulsion template.
AB  - Nanoporous ceramic with a unique pore structure was derived from an all
      hydrocarbon polymeric bicontinuous microemulsion (BmuE). The BmuE was designed to
      allow facile removal of one phase, resulting in a nanoporous polymer monolith
      with BmuE-like structure. The pores were filled with a commercially available,
      polymeric precursor to nonoxide, Si-based ceramics. Pyrolysis resulted in a
      monolith of nanoporous ceramic, stable to at least 1000 degrees C, with a BmuE
      like pore structure. The pore structure is disordered and 3-D continuous.
      Microscopy and gas sorption measurements suggest a well-defined pore size
      distribution spanning roughly 60-100 nm, sizes previously unattainable through
      related techniques.

PMID- 19159234
TI  - Templated nanocrystal-based porous TiO(2) films for next-generation
      electrochemical capacitors.
AB  - The advantages in using nanoscale materials for electrochemical energy storage
      are generally attributed to short diffusion path lengths for both electronic and
      lithium ion transport. Here, we consider another contribution, namely the charge
      storage from faradaic processes occurring at the surface, referred to as
      pseudocapacitive effect. This paper describes the synthesis and pseudocapacitive
      characteristics of block copolymer templated anatase TiO(2) thin films
      synthesized using either sol-gel reagents or preformed nanocrystals as building
      blocks. Both materials are highly crystalline and have large surface areas;
      however, the structure of the porosity is not identical. The different titania
      systems are characterized by a combination of small- and wide-angle X-ray
      diffraction/scattering, combined with SEM imaging and physisorption measurements.
      Following our previously reported approach, we are able to use the voltammetric
      sweep rate dependence to determine quantitatively the capacitive contribution to
      the current response. Considerable enhancement of the electrochemical properties
      results when the films are both made from nanocrystals and mesoporous. Such
      materials show high levels of capacitive charge storage and high insertion
      capacities. By contrast, when mesoscale porosity is created in a material with
      dense walls (rather than porous walls derived from the aggregation of
      nanocrystals), insertion capacities comparable to templated nanocrystal films can
      be achieved, but the capacitance is much lower. The results presented here
      illustrate the importance of pseudocapacitive behavior that develops in high
      surface area mesoporous oxide films. Such systems provide a new class of
      pseudocapacitive materials, which offer increased charge storage without
      compromising charge storage kinetics.

PMID- 19159235
TI  - Purification, pharmacological modulation, and biochemical characterization of
      interactors of endogenous human gamma-secretase.
AB  - Gamma-secretase is a unique intramembrane-cleaving protease complex, which
      cleaves the Alzheimer's disease-associated beta-amyloid precursor protein (APP)
      and a number of other type I membrane proteins. Human gamma-secretase consists of
      the catalytic subunit presenilin (PS) (PS1 or PS2), the substrate receptor
      nicastrin, APH-1 (APH-1a or APH-1b), and PEN-2. To facilitate in-depth
      biochemical analysis of gamma-secretase, we developed a fast and convenient
      multistep purification procedure for the endogenous enzyme. The enzyme was
      purified from HEK293 cells in an active form and had a molecular mass of
      approximately 500 kDa. Purified gamma-secretase was capable of producing the
      major amyloid-beta peptide (Abeta) species, such as Abeta40 and Abeta42, from a
      recombinant APP substrate in physiological ratios. Abeta generation could be
      modulated by pharmacological gamma-secretase modulators. Moreover, the
      Abeta42/Abeta40 ratio was strongly increased by purified PS1 L166P, an aggressive
      familial Alzheimer's disease mutant. Tandem mass spectrometry analysis revealed
      the consistent coisolation of several proteins with the known gamma-secretase
      core subunits. Among these were the previously described gamma-secretase
      interactors CD147 and TMP21 as well as other known interactors of these.
      Interestingly, the Niemann-Pick type C1 protein, a cholesterol transporter
      previously implicated in gamma-secretase-mediated processing of APP, was
      identified as a major copurifying protein. Affinity capture experiments using a
      biotinylated transition-state analogue inhibitor of gamma-secretase showed that
      these proteins are absent from active gamma-secretase complexes. Taken together,
      we provide an effective procedure for isolating endogenous gamma-secretase in
      considerably high grade, thus aiding further characterization of this pivotal
      enzyme. In addition, we provide evidence that the copurifying proteins identified
      are unlikely to be part of the active gamma-secretase enzyme.

PMID- 19159236
TI  - Simple chemical transformation of lignocellulosic biomass into furans for fuels
      and chemicals.
AB  - Lignocellulosic biomass is a plentiful and renewable resource for fuels and
      chemicals. Despite this potential, nearly all renewable fuels and chemicals are
      now produced from edible resources, such as starch, sugars, and oils; the
      challenges imposed by notoriously recalcitrant and heterogeneous lignocellulosic
      feedstocks have made their production from nonfood biomass inefficient and
      uneconomical. Here, we report that N,N-dimethylacetamide (DMA) containing lithium
      chloride (LiCl) is a privileged solvent that enables the synthesis of the
      renewable platform chemical 5-hydroxymethylfurfural (HMF) in a single step and
      unprecedented yield from untreated lignocellulosic biomass, as well as from
      purified cellulose, glucose, and fructose. The conversion of cellulose into HMF
      is unabated by the presence of other biomass components, such as lignin and
      protein. Mechanistic analyses reveal that loosely ion-paired halide ions in DMA
      LiCl are critical for the remarkable rapidity (1-5 h) and yield (up to 92%) of
      this low-temperature (<or=140 degrees C) process. The simplicity of this chemical
      transformation of lignocellulose contrasts markedly with the complexity of extant
      bioprocesses and provides a new paradigm for the use of biomass as a raw material
      for a renewable energy and chemical industries.

PMID- 19159237
TI  - Efficient intramolecular general-acid catalysis of the reactions of alpha-effect
      nucleophiles and ammonia oxide with a phosphate triester.
AB  - The S(N)2(P) reactions with alpha-effect nucleophiles of the cationic form 1.H(+)
      of phosphate triester diethyl 8-(N,N-dimethylamino)-1-naphthyl phosphate are
      catalyzed by the neighboring dimethylammonium group, with accelerations as high
      as 10(6). Hydroxylamine and its N-methyl and N,N-dimethyl derivatives, which
      react through oxygen, we presume by way of the zwitterionic ammonia oxide
      tautomers, are of special interest. The alpha-effect and the efficient general
      acid catalysis in this system are mutually reinforcing. The alpha-effect is
      greater for the reactions of the triester than for the corresponding mono- and
      diesters and qualitatively different for hydroxylamines RR'NOH, where the likely
      role of the ammonia oxide tautomer NH(3)(+)-O(-) is evaluated by ab initio
      calculations. The initial phosphorus-containing product NH(2)OPO(OEt)(2) reacts
      further with hydroxylamine to generate diethyl phosphate and diimide, identified
      by its disproportionation to hydrazine and N(2) and its reducing potential.

PMID- 19159238
TI  - New findings in the chemistry of iron carbonyls: the previously unreported [H(4
      n)Fe4(CO)12]n- (n = 1, 2) series of clusters, which fills the gap with ruthenium
      and osmium.
AB  - The new [HFe(4)(CO)(12)](3-) cluster anion has been obtained in high yields by
      reduction of [Fe(4)(CO)(13)](2-) or [HFe(3)(CO)(11)](-) with a 6 M
      methylalcoholic KOH solution under a nitrogen atmosphere and isolated with
      miscellaneous tetrasubstituted ammonium salts. The [NEt(4)](3)[HFe(4)(CO)(12)]
      salt has been characterized by IR, (1)H and (13)C NMR, electrospray ionization
      mass spectrometry, and X-ray studies. Investigation of its protonation reaction
      afforded spectroscopic proof for the existence of its unstable isomeric
      [HFe(4)(CO)(11)(CO-H)](2-) and [H(2)Fe(4)(CO)(12)](2-) conjugated acids. The
      latter is probably isostructural with the [H(2)Ru(4)(CO)(12)](2-) congener. The
      nature of the first protonation product as a [HFe(4)(CO)(11)(CO-H)](2-) adduct,
      involving an oxygen-bound proton, has been corroborated by the preparation and
      spectroscopic characterization of the corresponding [HFe(4)(CO)(11)(CO-Me)](2-)
      dianion. The above findings demonstrate that protonation of a CO-shielded
      polynuclear metal anion initially occurs on one oxygen atom and then the oxygen
      bound proton migrates to the metal cage. Finally, [HFe(4)(CO)(12)](3-) and its
      [H(2)Fe(4)(CO)(12)](2-) conjugate acid fill the previously existing gap between
      the chemistry of iron carbonyls and ruthenium and osmium congeners.

PMID- 19159239
TI  - Systematic thermodynamics of hydration (and of solvation) of inorganic solids.
AB  - The thermodynamics of the formation of solid and liquid inorganic hydrates and
      ammoniates is examined. In earlier studies, average values of the Gibbs energy of
      reaction, Delta(r)G, assuming a constant additivity per mole of bound water, have
      been obtained and have suggested that hydration is always marginally
      thermodynamically favorable. More detailed consideration now demonstrates that
      the mean value of Delta(r)G per mole of water, from anhydrous parent to hydrate
      within a sequence, increases consistently toward zero, becoming progressively
      less favorable as the degree of hydration, n, increases, and broadly independent
      of any structural features of the materials. Furthermore, the consistent behavior
      suggests that missing intermediate hydrates in hydrate sequences are likely to be
      thermodynamically stable, even if difficult to prepare, isolate, or measure.The
      behavior of ammoniates is similar but less regular, the irregularity being
      ascribed to a wider range of interactions within the solid ammoniates than in the
      hydrates. The "Ostwald Rule of Stages" suggests that the first precipitate from a
      supersaturated solution is usually a metastable phase, having an intermediate
      value of the Gibbs energy between that of the anhydrous parent and of the
      thermodynamically stable phase, then progressing to the stable phase with the
      lowest Gibbs energy, implying kinetic rather than thermodynamic control of the
      sequence of precipitation. The implications for hydrate formation are briefly
      considered.

PMID- 19159241
TI  - Inorganic frameworks from selenidotetrelate anions [T2Se6]4- (T = Ge, Sn):
      synthesis, structures, and ionic conductivity of [K2(H2O)3][MnGe4Se10] and
      (NMe4)2[MSn4Se10] (M = Mn, Fe).
AB  - Syntheses, structures, and physical properties of three inorganic framework
      compounds [K(2)(H(2)O)(3)][MnGe(4)Se(10)] (1), (NMe(4))(2)[MnSn(4)Se(10)] (2),
      and (NMe(4))(2)[FeSn(4)Se(10)] (3) are presented. The title compounds are based
      on a prominent open framework anionic structure; in these cases, however, they
      contain K(+), the smallest type of counterion to be included so far (1), or
      represent Sn analogues (2, 3). Both changes with respect to related compounds are
      reflected in peculiar physical properties, such as ion conductivity or relatively
      small band gaps.

PMID- 19159240
TI  - Structure of the biliverdin radical intermediate in phycocyanobilin:ferredoxin
      oxidoreductase identified by high-field EPR and DFT.
AB  - The cyanobacterial enzyme phycocyanobilin:ferredoxin oxidoreductase (PcyA)
      catalyzes the two-step four-electron reduction of biliverdin IXalpha to
      phycocyanobilin, the precursor of biliprotein chromophores found in
      phycobilisomes. It is known that catalysis proceeds via paramagnetic radical
      intermediates, but the structure of these intermediates and the transfer pathways
      for the four protons involved are not known. In this study, high-field electron
      paramagnetic resonance (EPR) spectroscopy of frozen solutions and single crystals
      of the one-electron reduced protein-substrate complex of two PcyA mutants D105N
      from the cyanobacteria Synechocystis sp. PCC6803 and Nostoc sp. PCC7120 are
      examined. Detailed analysis of Synechocystis D105N mutant spectra at 130 and 406
      GHz reveals a biliverdin radical with a very narrow g tensor with principal
      values 2.00359(5), 2.00341(5), and 2.00218(5). Using density-functional theory
      (DFT) computations to explore the possible protonation states of the biliverdin
      radical, it is shown that this g tensor is consistent with a biliverdin radical
      where the carbonyl oxygen atoms on both the A and the D pyrrole rings are
      protonated. This experimentally confirms the reaction mechanism recently proposed
      (Tu, et al. Biochemistry 2007, 46, 1484).

PMID- 19159242
TI  - Matrix Isolation and ab initio study of the noncovalent complexes between
      formamide and acetylene.
AB  - Matrix isolation spectroscopy in combination with ab initio calculations is a
      powerful technique for the identification of weakly bound intermolecular
      complexes. Here, weak complexes between formamide and acetylene are studied, and
      three 1:1 complexes with binding energies of -2.96, -2.46, and -1.79 kcal/mol
      have been found at the MP2 level of theory (MP2/cc-pVTZ + ZPE + BSSE). The two
      most stable dimers A and B are identified in argon and nitrogen matrices by
      comparison between the experimental and calculated infrared frequencies. Both
      complexes are stabilized by the formamide C=O...HC acetylene and H...pi
      interactions. Large shifts have been observed experimentally for the C-H
      stretching vibrations of the acetylene molecule, in very good agreement with the
      calculated values. Eight 1:2 FMA-acetylene trimers (T-A to T-H) with binding
      energies between -5.44 and -2.62 kcal/mol (MP2/aug-cc-pVDZ + ZPE + BSSE) were
      calculated. The two most stable trimers T-A and T-B are very close in energy and
      have similar infrared spectra. Several weak bands that are in agreement with the
      calculated frequencies of the trimers T-A and T-B are observed under matrix
      isolation conditions. However, the differences are too small for a definitive
      assignment.

PMID- 19159243
TI  - Direct amidation of aldoses and decarboxylative amidation of alpha-keto acids: an
      efficient conjugation method for unprotected carbohydrate molecules.
AB  - With use of iodine as an appropriate oxidant, unprotected and unmodified aldoses
      undergo oxidative amidation with a variety of functionalized amines, alpha-amino
      esters, and peptides, whereas KDO, sialic acid, and other alpha-keto acids
      proceed with oxidative decarboxylation followed by in situ amidation. Glycoside
      bond and many other functional groups are inert under such mild reaction
      conditions. This reaction protocol for direct ligation of carbohydrate molecules
      looks promising in the development of a general and efficient synthesis of
      glycoconjugates.

PMID- 19159244
TI  - Synthesis and characterization of nitroaromatic peptoids: fine tuning peptoid
      secondary structure through monomer position and functionality.
AB  - N-substituted glycine oligomers, or peptoids, have emerged as an important class
      of foldamers for the study of biomolecular interactions and for potential use as
      therapeutic agents. However, the design of peptoids with well-defined
      conformations a priori remains a formidable challenge. New approaches are
      required to address this problem, and the systematic study of the role of
      individual monomer units in the global peptoid folding process represents one
      strategy. Here, we report our efforts toward this approach through the design,
      synthesis, and characterization of peptoids containing nitroaromatic monomer
      units. This work required the synthesis of a new chiral amine building block, (S)
      1-(2-nitrophenyl)ethanamine (s2ne), which could be readily installed into
      peptoids using standard solid-phase peptoid synthesis techniques. We designed a
      series of peptoid nonamers that allowed us to probe the effects of this
      relatively electron-deficient and sterically encumbered alpha-chiral side chain
      on peptoid structure, namely, the peptoid threaded loop and helix. Circular
      dichroism spectroscopy of the peptoids revealed that the nitroaromatic monomer
      has a significant effect on peptoid secondary structure. Specifically, the
      threaded loop structure was disrupted in a nonamer containing alternating N-(S)-1
      phenylethylglycine (Nspe) and Ns2ne monomers, and the major conformation was
      helical instead. Indeed, placement of a single Ns2ne at the N-terminal position
      of (Nspe)(9) resulted in a destabilized form of the threaded loop structure
      relative to the homononamer (Nspe)(9). Conversely, we observed that incorporation
      of N-(S)-1-(4-nitrophenyl)ethylglycine (Nsnp, a p-nitro monomer) at the N
      terminal position stabilized the threaded loop structure relative to (Nspe)(9).
      Additional experiments revealed that nitroaromatic side chains can influence
      peptoid nonamer folding by modulating the strength of key intramolecular hydrogen
      bonds in the peptoid threaded loop structure. Steric interactions were also
      implicated for the Ns2ne monomer. Overall, this study provides further evidence
      that aromatic side-chain structure, even if perturbed in a single monomer unit,
      can strongly influence local peptoid backbone conformation.

PMID- 19159245
TI  - Ferroelectric lithography: bottom-up assembly and electrical performance of a
      single metallic nanowire.
AB  - We report on both the assembly of noble-metal nanowires by means of the
      nanotechnological and large-scale integrable approach of ferroelectric
      lithography and their performance testing upon electrical transport. Our results
      on LiNbO(3) single crystal templates show that the deposition of different
      elemental metals from ionic solutions by photochemical reduction is confined to
      the ferroelectric 180 degrees domain walls. Current-voltage-characteristics
      recorded from such nanowires of typically 30-300 microm in length revealed an
      Ohmic behavior that even improved with time. Additionally, we also examined the
      local topographic and potentiostatic properties of such wires using dynamic
      scanning force microscopy in combination with Kelvin probe force microscopy.

PMID- 19159246
TI  - Raman scattering from nonequilibrium molecular conduction junctions.
AB  - Raman scattering is a potentially important probe of structure, dynamics, and
      thermal properties of single-molecule conduction junctions. We combine a
      nonequilibrium Green's function description of the junction with a generalized
      scattering theory of the Raman process, which provides the first theoretical
      description of Raman scattering from such systems. The voltage dependence of the
      Raman flux shows a characteristic behavior at the conductance threshold resulting
      from (a) partial populations in the ground and excited molecular levels that give
      rise to two scattering pathways as well as interference between them and (b)
      junction heating that affects the Raman intensities. Comparing "effective
      temperatures" obtained from Raman scattering and heat balance serves to establish
      the integrity of this concept for nonequilibrium junctions.

PMID- 19159247
TI  - Polarized surface-enhanced Raman spectroscopy from molecules adsorbed in nano
      gaps produced by electromigration in silver nanowires.
AB  - Uniform nanogaps were produced in silver nanowires previously fabricated by AC
      electrodeposition in porous anodic alumina templates and released by dissolving
      the oxide matrix. Configuring the nanowires with electrodes and passing current
      through them created nanogaps by electromigration. Uniform nanogaps approximately
      perpendicular to the axes of the nanowires were produced with widths in the range
      approximately 17 to approximately 40 nm. Gaps as small as 5 nm but with less
      uniform geometries could also be produced in this manner. A heuristic model, in
      which electromigrative and diffusional effects are included, is used to relate
      the size of the nanogap produced to the local resistance of the region in the
      nanowire where the gap ultimately forms. Intense surface-enhanced Raman spectra
      were observed from Rhodamine 6G adsorbed on the nanowire in the gap. For gaps
      that uniformly divided the nanowire across its width, the surface enhanced Raman
      spectroscopy intensity was maximum when the electric vector of the exciting light
      was oriented across the gap, as predicted by electromagnetic enhancement
      calculations.

PMID- 19159250
TI  - Catalyst-free growth of single-crystal silicon and germanium nanowires.
AB  - We report metal-free synthesis of high-density single-crystal elementary
      semiconductor nanowires with tunable electrical conductivities and systematic
      diameter control with narrow size distributions. Single-crystal silicon and
      germanium nanowires were synthesized by nucleation on nanocrystalline seeds and
      subsequent one-dimensional anisotropic growth without using external catalyst.
      Systematic control of the diameters with tight distribution and tunable doping
      concentration were realized by adjusting the growth conditions, such as growth
      temperature and ratio of precursor partial pressures. We also demonstrated both n
      type and ambipolar field effect transistors using our undoped and phosphorus
      doped metal-free silicon nanowires, respectively. This growth approach offers a
      method to eliminate potential metal catalyst contamination and thus could serve
      as an important point for further developing nanowire nanoelectronic devices for
      applications.

PMID- 19159251
TI  - Self-deactivation of single-walled carbon nanotube growth studied by in situ
      Raman measurements.
AB  - In situ Raman measurements were used to investigate the kinetics and the self
      deactivation of the growth of single-walled carbon nanotubes during catalytic
      chemical vapor deposition. The kinetics appear controlled by the mass-transport
      of the gaseous precursor at low precursor pressure and high temperature and by
      the catalytic decomposition of the precursor at high precursor pressure and low
      temperature. The initial growth rate and the lifetime display inversely
      correlated evolutions with the growth parameters. In addition, we measured the
      activation energy for the healing of defects during the growth and discuss it in
      comparison to the apparent activation energies measured for the initial growth
      rate and the lifetime. Our results support that the healing of the edge defects
      controls both the crystalline order and the growth lifetime.

PMID- 19159248
TI  - Internally cationic polyamidoamine PAMAM-OH dendrimers for siRNA delivery: effect
      of the degree of quaternization and cancer targeting.
AB  - A novel cancer targeted, internally cationic and surface neutral polyamidoamine
      (PAMAM) dendrimer, was designed, synthesized, and evaluated as a nanocarrier for
      the targeted intracellular delivery of siRNA. The dendrimer contained a synthetic
      analog of Luteinizing hormone-releasing hormone as cancer targeting moiety. The
      proposed delivery system possesses the following advantages: (1) internal
      cationic charges for complexation with siRNA and enhanced siRNA protection; (2)
      low cytotoxicity; (3) lesser degree of quaternization offering free tertiary
      amines for potential proton sponge effect; and (4) targeting specifically to
      cancer cells for enhancing siRNA uptake and efficiency and potential limitation
      of adverse side effects of chemotherapy on healthy organs. Both nontargeted and
      targeted dendrimer-siRNA complexes formed compact nanometer size spherical
      particles, exhibited very low cytotoxicity even at the higher concentration, and
      efficiently penetrated cancer cells in vitro. However, only the targeted
      dendrimer-siRNA complex was able to substantially decrease the expression of a
      targeted BCL2 gene.

PMID- 19159252
TI  - Numerical investigations into the tensile behavior of TiO(2) nanowires:
      structural deformation, mechanical properties, and size effects.
AB  - The mechanisms governing the tensile behavior of TiO(2) nanowires were studied by
      molecular dynamics simulations. Nanowires below a threshold diameter of about 10
      A transformed into a completely disordered structure after thermodynamic
      equilibration, whereas thicker nanowires retained their crystalline core. Initial
      elastic tensile deformation was effected by the reconfiguration of surface atoms
      while larger elongations resulted in continuous cycles of Ti-O bond
      straightening, bond breakage, inner atomic distortion, and necking until rupture.
      Nanowires have much better mechanical properties than bulk TiO(2). Nanowires
      below the threshold diameter exhibit extraordinarily high stiffness and toughness
      and are more sensitive to strain rate.

PMID- 19159254
TI  - 6Pi e- versus 8pi e- electrocyclization of 1-aryl- and heteroaryl-substituted
      (1Z,3Z)-1,3,5-hexatrienes: a matter of aromaticity.
AB  - Peri selectivity of the electrocyclization of 1-aryl- and heteroaryl-substituted
      (1Z,3Z)-1,3,5-hexatrienes, obtained by Ru-catalyzed linear coupling of 1,6-diynes
      to Z-propenyl(hetero)arenes, can be efficiently modulated depending on the
      aromaticity of the (hetero)arene: 1,3,5-hexatrienyl(hetero)arenes give 8pi e-
      electrocyclization with the exception of 1,3,5-hexatrienylbenzenes, which give
      6pi e- electrocyclization.

PMID- 19159253
TI  - Absolute configuration of the alpha,omega-bifunctionalized sphingolipid
      leucettamol A from Leucetta microrhaphis by deconvoluted exciton coupled CD.
AB  - The configuration of leucettamol A (1), a known long-chain "two-headed"
      sphingolipid (dimeric sphingolipid) from the marine sponge Leucetta microrhaphis,
      was determined by conversion to an N,N',O,O'-tetrabenzoyl derivative, measurement
      of the exciton coupled circular dichroism spectrum (ECCD), and quantitative
      analysis by deconvolution of superposed exciton couplets. Contrary to the earlier
      assignment that claimed leucettamol A (1) was racemic, the CD approach
      unambiguously reveals the natural product is chiral and optically active and
      displays pseudo-C(2) symmetry. The configuration of each end of the chain has
      erythro stereochemistry with an absolute configuration of 2R,3S,28S,29R. We show
      that deconvolution ECCD reliably predicts erythro versus threo vicinal amino
      alcohols in all cases with greater sensitivity (<5 nmol) compared to (1)H NMR J
      based methods and provides verification of optical purity and unequivocal
      elucidation of absolute configuration in this difficult class of natural
      products.

PMID- 19159255
TI  - Mitsunobu approach to the synthesis of optically active alpha,alpha-disubstituted
      amino acids.
AB  - Chiral tertiary alpha-hydroxy esters of known stereochemical configuration were
      transformed to alpha-azido esters by Mitsunobu reaction with HN3. Optimization of
      this reaction was shown to proceed at room temperature with high chemical yield
      using 1,1-(azodicarbonyl)dipiperidine (ADDP) and trimethylphosphine (PMe3).
      Complete inversion of configuration was observed at the alpha-carbon. Several
      alpha,alpha-disubstituted amino acids were synthesized in high overall chemical
      yield and optical purity.

PMID- 19159256
TI  - Stereocontrolled synthesis of oligoribonucleoside phosphorothioates by an
      oxazaphospholidine approach.
AB  - Oligoribonucleoside phosphorothioates (PS-ORNs) stereodefined at the phosphorus
      atoms were synthesized on solid support. Thermal denaturating experiments of the
      resultant PS-ORNs showed that a backbone consisting of (Sp)-PS-linkages as well
      as stereorandom PS-linkages had an unexpectedly large destabilizing effect on a
      PS-ORN-ORN duplex, whereas a backbone consisting of (Rp)-PS-linkages slightly
      stabilized a duplex.

PMID- 19159257
TI  - Catalytic hydrodefluorination of aromatic fluorocarbons by ruthenium N
      heterocyclic carbene complexes.
AB  - The catalytic hydrodefluorination (HDF) of hexafluorobenzene, pentafluorobenzene,
      and pentafluoropyridine with alkylsilanes is catalyzed by the ruthenium N
      heterocyclic carbene (NHC) complexes Ru(NHC)(PPh(3))(2)(CO)H(2) (NHC = SIMes (1,3
      bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene) 13, SIPr (1,3-bis(2,6
      diisopropylphenyl)imidazolin-2-ylidene) 14, IPr (1,3-bis(2,6
      diisopropylphenyl)imidazol-2-ylidene) 15, IMes (1,3-bis(2,4,6
      trimethylphenyl)imidazol-2-ylidene) 16). Catalytic activity follows the order 15
      > 13 > 16 > 14, with 15 able to catalyze the HDF of C(6)F(5)H with Et(3)SiH with
      a turnover number of up to 200 and a turnover frequency of up to 0.86 h(-1). The
      catalytic reactions reveal (i) a novel selectivity for substitution at the 2
      position in C(6)F(5)H and C(5)F(5)N, (ii) formation of deuterated fluoroarene
      products when reactions are performed in C(6)D(6) or C(6)D(5)CD(3), and (iii) a
      first-order dependence on [fluoroarene] and zero-order relationship with respect
      to [R(3)SiH]. Mechanisms are proposed for HDF of C(6)F(6) and C(6)F(5)H, the
      principal difference being that the latter occurs by initial C-H rather than C-F
      activation.

PMID- 19159258
TI  - Intramolecular electron-transfer rates in mixed-valence triarylamines:
      measurement by variable-temperature ESR spectroscopy and comparison with optical
      data.
AB  - The electron spin resonance spectra of the radical cations of 4,4'-bis[di(4
      methoxyphenyl)amino]tolane, E-4,4'-bis[di(4-methoxyphenyl)amino]stilbene, and E,E
      1,4-bis{4-[di(4-methoxyphenyl)amino]styryl}benzene in dichloromethane exhibit
      five lines over a wide temperature range due to equivalent coupling to two 14N
      nuclei, indicating either delocalization between both nitrogen atoms or rapid
      intramolecular electron transfer on the electron spin resonance time scale. In
      contrast, those of the radical cations of 1,4-bis{4-[di(4
      methoxyphenyl)amino]phenylethynyl}benzene and E,E-1,4-bis{4-[di(4-n
      butoxyphenyl)amino]styryl}-2,5-dicyanobenzene exhibit line shapes that vary
      strongly with temperature, displaying five lines at room temperature and only
      three lines at ca. 190 K, indicative of slow electron transfer on the electron
      spin resonance time scale at low temperatures. The rates of intramolecular
      electron transfer in the latter compounds were obtained by simulation of the
      electron spin resonance spectra and display an Arrhenius temperature dependence.
      The activation barriers obtained from Arrhenius plots are significantly less than
      anticipated from Hush analyses of the intervalence bands when the diabatic
      electron-transfer distance, R, is equated to the N[symbol: see text]N distance.
      Comparison of optical and electron spin resonance data suggests that R is in fact
      only ca. 40% of the N[symbol: see text]N distance, while the Arrhenius prefactor
      indicates that the electron transfer falls in the adiabatic regime.

PMID- 19159259
TI  - On the mechanism of B(C6F5)3-catalyzed direct hydrogenation of imines: inherent
      and thermally induced frustration.
AB  - The reaction mechanism for the transition metal free direct hydrogenation of
      bulky imines catalyzed by the Lewis acid B(C6F5)3 is investigated in detail by
      quantum chemical calculations. A recently introduced mechanistic model of
      heterolytic hydrogen splitting that is based on noncovalent association of bulky
      Lewis acid-base pairs is shown to account for the reactivity of imine-borane as
      well as amine-borane systems. Possible catalytic cycles are examined, and the
      results provide solid support for the imine reduction pathway proposed from
      experimental observations. In addition, the feasibility of an autocatalytic route
      initiated by amine-borane hydrogen cleavage is demonstrated. Conceptual issues
      regarding the notion of frustration are also discussed. The observed reactivity
      is interpreted in terms of thermally induced frustration, which refers to thermal
      activation of strained dative adducts of bulky Lewis donor-acceptor pairs to
      populate their reactive frustrated complex forms.

PMID- 19159261
TI  - Ru(II) complexes of N-alkylated TsDPEN ligands in asymmetric transfer
      hydrogenation of ketones and imines.
AB  - N-Alkylated TsDPEN derivatives bearing a small alkyl group act as highly
      efficient ligands in Ru(II) complexes for the asymmetric transfer hydrogenation
      of imines and ketones. A larger alkyl group serves to significantly reduce the
      activity of the catalyst; however, high enantiomeric excesses are still obtained.
      An X-ray crystal structure of the N-benzyl derivative reveals a conformation that
      permits hydrogen transfer through a six-membered transition state. A transition
      state structure for the imine reduction process is proposed.

PMID- 19159260
TI  - Mapping the interaction between the hemophore HasA and its outer membrane
      receptor HasR using CRINEPT-TROSY NMR spectroscopy.
AB  - The first step of heme acquisition by Gram-negative pathogenic bacteria through
      the so-called heme acquisition system, Has, requires delivery of the heme from
      the extracellular hemophore protein HasA to a specific outer membrane receptor,
      HasR. CRINEPT-TROSY NMR experiments in DPC micelles were here used to obtain
      information on the intermediate HasA-HasR complex in solution. A stable protein
      protein adduct is detected both in the presence and in the absence of heme.
      Structural information on the complexed form of HasA is obtained from chemical
      shift mapping and statistical analysis of the spectral fingerprint of the protein
      NMR spectra obtained under different conditions. This approach shows the
      following: (i) only three different conformations are possible for HasA in
      solution: one for the isolated apoprotein, one for the isolated holoprotein, and
      one for the complexed protein, that is independent of the presence of the heme;
      (ii) the structure of the hemophore in the complex resembles the open
      conformation of the apoprotein; (iii) the surface contact area between HasA and
      HasR is independent of the presence of the heme, involving loop L1, loop L2, and
      the beta2-beta6 strands; (iv) upon complex formation the heme group is
      transferred from holoHasA to HasR.

PMID- 19159262
TI  - Interspecific variation in critical patch size and gap-crossing ability as
      determinants of geographic range size distributions.
AB  - How biological processes such as reproduction and dispersal relate to the size of
      species' geographic ranges constitutes a major challenge in spatial ecology and
      biogeography. Here we develop a spatially explicit theoretical framework that
      links fundamental population-level ecological traits (e.g., rates of dispersal
      and population growth or decay) with landscape heterogeneity to derive estimates
      of species' geographic range sizes and, further, distributions of geographic
      range sizes across species. Although local (patch-scale) population dynamics in
      this model are completely deterministic, we consider a fragmented landscape of
      patches and gaps in which the spatial heterogeneity is itself stochastic. This
      stochastic spatial structure, which juxtaposes landscape-level patch and gap
      characteristics against population-level critical patch sizes and maximum gap
      crossing abilities, determines how far a novel species can spread from its
      evolutionary origin. Given reasonable assumptions about landscape structure and
      about the distribution of critical patch sizes and critical gap lengths among
      species, we obtain distributions of geographic range sizes that are qualitatively
      similar to those routinely found in nature (e.g., many species with small
      geographic ranges). Collectively, our results suggest that both interspecific
      differences in population-level traits and the landscapes through which species
      spread help determine patterns of occupancy and geographic extent.

PMID- 19159263
TI  - Rhodium(I)-catalyzed synthesis of indoles: amino-Claisen rearrangement of N
      propargylanilines.
AB  - Mild and facile preparations of 2-substituted or 2,3-disubstituted indole
      compounds were achieved by RhH(CO)(Ph(3)P)(3) (4-10 mol %)-catalyzed reaction of
      N-propargylanilines in hexafluoroisopropyl alcohol (HFIP). The formation of
      indoles was proven to be derived from an o-allenylaniline intermediate, which was
      generated by the Rh(I)-catalyzed amino-Claisen rearrangement of N
      propargylanilines. The catalytic system is also available for the one-pot
      synthesis of indoles by reacting N-alkylaniline (1 equiv) with propargyl bromide
      (1.3 equiv) in the presence of K(2)CO(3) (3 equiv) in HFIP. The active catalyst
      was proven to be [Rh(CO)(Ph(3)P)(2)]OCH(CF(3))(2) generated in situ from
      RhH(CO)(Ph(3)P)(3) and HFIP. The structure of [Rh(CO)(Ph(3)P)(2)]OCH(CF(3))(2)
      was confirmed by single-crystal X-ray crystallographic analysis.

PMID- 19159264
TI  - Deterministic limit of stochastic chemical kinetics.
AB  - An analysis is presented of the approximating assumptions that underlie a
      recently proposed derivation of the traditional deterministic reaction rate
      equation from a discrete-stochastic formulation of chemical kinetics. It is shown
      that if the system is close enough to the thermodynamic limit, in which the
      molecular populations and the containing volume all approach infinity in such a
      way that the molecular concentrations remain finite, then the required
      approximating assumptions will be justified for practically all spatially
      homogeneous systems that one is likely to encounter.

PMID- 19159266
TI  - AP7, a partially disordered pseudo C-RING protein, is capable of forming
      stabilized aragonite in vitro.
AB  - AP7 is an extracellular aragonite-associated protein of the nacre layer of the
      mollusk Haliotis rufescens and possesses a 36-amino acid C-terminal domain that
      exhibits sequence homology to the C subclass of the RING domain intracellular
      protein family. We report here novel findings which implicate AP7 as a member of
      the intrinsically disordered protein class (IDP) and reveal new aspects of AP7
      mineralization activity. AP7 is partially disordered but can undergo additional
      folding in the presence of TFE. AP7 binds Zn(II) ions in a non-tetracoordinate
      complex but does not require Zn(II) either for folding or for in vitro function.
      In addition to limiting calcite crystal growth, AP7 is also observed to induce
      aggregate formation within in vitro mineralization assays, and these aggregates
      are either amorphous (type A) or crystalline (type B) in appearance. The type A
      aggregate displays an irregular morphology and round, dark, electron dense
      deposits that do not give rise to a diffraction pattern. In contrast, the type B
      aggregates possess either organized parallel crystal clusters or highly dense
      hexagonal clusters that are confirmed by electron diffraction to be aragonite.
      This stabilization of aragonite is remarkable in that it occurred in the presence
      of AP7 alone and did not require typical aragonite stabilization agents such as
      Mg(II), other nacre proteins, or an organized organic matrix. The ability of a
      partially disordered C-RING protein to perform inorganic phase stabilization
      represents a new twist on both the RING domain and IDP stories, and this process
      of aggregate formation may provide an important clue with regard to the protein
      mediated nacre formation process.

PMID- 19159265
TI  - Subunit structure of benzylsuccinate synthase.
AB  - Benzylsuccinate synthase is a member of the glycyl radical family of enzymes. It
      catalyzes the addition of toluene to fumarate to form benzylsuccinate as the
      first step in the anaerobic pathway of toluene fermentation. The enzyme comprises
      three subunits, alpha, beta, and gamma, that in Thauera aromatica strain T1 are
      encoded by the tutD, tutG, and tutF genes, respectively. The large alpha-subunit
      contains the essential glycine and cysteine residues that are conserved in all
      glycyl radical enzymes. However, the function of the small beta- and gamma
      subunits has remained unclear. We have overexpressed all three subunits of
      benzylsuccinate synthase in Escherichia coli, both individually and in
      combination. Coexpression of the gamma-subunit (but not the beta-subunit) is
      essential for efficient expression of the alpha-subunit. The benzylsuccinate
      synthase complex lacking the glycyl radical could be purified as an
      alpha(2)beta(2)gamma(2) hexamer by nickel affinity chromatography through a
      "His(6)" affinity tag engineered onto the C-terminus of the alpha-subunit.
      Unexpectedly, BSS was found to contain two iron-sulfur clusters, one associated
      with the beta-subunit and the other with the gamma-subunit that appear to be
      necessary for the structural integrity of the complex. The spectroscopic
      properties of these clusters suggest that they are most likely [4Fe-4S] clusters.
      Removal of iron with chelating agents results in dissociation of the complex;
      similarly, a mutant gamma-subunit lacking the [4Fe-4S] cluster is unable to
      stabilize the alpha-subunit when the proteins are coexpressed.

PMID- 19159267
TI  - One- versus two-electron oxidation with peroxomonosulfate ion: reactions with
      iron(II), vanadium(IV), halide ions, and photoreaction with cerium(III).
AB  - The kinetics of the redox reactions of the peroxomonosulfate ion (HSO(5)(-)) with
      iron(II), vanadium(IV), cerium(III), chloride, bromide, and iodide ions were
      studied. Cerium(III) is only oxidized upon illumination by UV light and
      cerium(IV) is produced in a photoreaction with a quantum yield of 0.33 +/- 0.03.
      Iron(II) and vanadium(IV) are most probably oxidized through one-electron
      transfer producing sulfate ion radicals as intermediates. The halide ions are
      oxidized in a formally two-electron process, which most likely includes oxygen
      atom transfer. Comparison with literature data suggests that the activation
      entropies might be used as indicators distinguishing between heterolytic and
      homolytic cleavage of the peroxo bond in the redox reactions of HSO(5)(-).

PMID- 19159268
TI  - The first octahedral cluster complexes with terminal formate ligands: synthesis,
      structure, and properties of K4[Re6S8(HCOO)6] and Cs4[Re6S8(HCOO)6].
AB  - The hexarhenium anionic cluster complex with terminal formate ligands
      [Re6S8(HCOO)6]4- was obtained by the room-temperature reaction between
      [Re6S8(OH)6]4- and formic acid in an aqueous solution. The cluster was
      crystallized as a potassium or cesium salt and characterized by X-ray single
      crystal diffraction and elemental analyses, IR, 1H NMR, UV/vis, and luminescence
      spectroscopies. In particular, the emission quantum yield of the potassium salt
      of the Re6 cluster anion in the solid phase was determined for the first time.
      The electronic structures of [Re6S8(HCOO)6]4- and [Re6S8(OH)6]4- were also
      elucidated by DFT calculations.

PMID- 19159269
TI  - Measuring temperature gradients over nanometer length scales.
AB  - When a quantum dot is subjected to a thermal gradient, the temperature of
      electrons entering the dot can be determined from the dot's thermocurrent if the
      conductance spectrum and background temperature are known. We demonstrate this
      technique by measuring the temperature difference across a 15 nm quantum dot
      embedded in a nanowire. This technique can be used when the dot's energy states
      are separated by many kT and will enable future quantitative investigations of
      electron-phonon interaction, nonlinear thermoelectric effects, and the efficiency
      of thermoelectric energy conversion in quantum dots.

PMID- 19159270
TI  - Reaction mechanism of the dinuclear zinc enzyme N-acyl-L-homoserine lactone
      hydrolase: a quantum chemical study.
AB  - N-acyl-L-homoserine lactone hydrolase (AHL lactonase) is a dinuclear zinc enzyme
      responsible for the hydrolytic ring opening of AHLs, disrupting quorum sensing in
      bacteria. The reaction mechanism is investigated using hybrid density functional
      theory. A model of the active site is designed on the basis of the X-ray crystal
      structure, and stationary points along the reaction pathway are optimized and
      analyzed. Two possible mechanisms based on two different substrate orientations
      are considered. The calculations give support to a reaction mechanism that
      involves two major chemical steps: nucleophilic attack on the substrate carbonyl
      carbon by the bridging hydroxide and ring opening by direct ester C-O bond
      cleavage. The roles of the two zinc ions are analyzed. Zn1 is demonstrated to
      stabilize the charge of the tetrahedral intermediate, thereby facilitating the
      nucleophilic attack, while Zn2 stabilizes the charge of the alkoxide resulting
      from the ring opening, thereby lowering the barrier for the C-O bond cleavage.

PMID- 19159271
TI  - Interactions between DMPC liposomes and the serum blood proteins HSA and IgG.
AB  - The interaction between two serum blood proteins, namely human serum albumin
      (HSA) and human immunoglobulin G (IgG), with 1,2-dimyristoyl-sn-glycero-3
      phosphatidylcholine (DMPC) liposomes has been studied in detail using dynamic
      light scattering, flow cytometry, enzyme-linked immunosorbent assay (ELISA),
      electrophoretic mobility, differential scanning calorimetry (DSC), and surface
      tension measurements. HSA and IgG interact with liposomes forming molecular
      aggregates that remain stable at protein concentrations beyond those of total
      liposome coverage. Both HSA and IgG penetrate into the liposome bilayer. An ELISA
      assay indicates that the Fc region of IgG is the one that is immersed in the DMPC
      membrane. The liposome-protein interaction is mainly of electrostatic nature, but
      an important hydrophobic contribution is also present.

PMID- 19159272
TI  - Cytotoxic guanidine alkaloids from Pterogyne nitens.
AB  - As part of a bioprospecting program aimed at the discovery of potential
      anticancer drugs, two new guanidine-type alkaloids, nitensidines D and E (1, 2),
      and the known pterogynine (3), pterogynidine (4), and galegine (5), were isolated
      from the leaves of Pterogyne nitens. The structures of 1 and 2 were established
      on the basis of spectroscopic data interpretation. These compounds were tested
      against a small panel of human cancer cell lines. Compound 2 exhibited
      cytotoxicity for HL-60 (human myeloblastic leukemia) and SF-245 (human
      glioblastoma) cells.

PMID- 19159273
TI  - Sesquiterpenoids and phenylpropanoids from pericarps of Illicium oligandrum.
AB  - Four new merrillianin-type sesquiterpenes, oligandrumins A-D (1-4), two new seco
      prezizaane-type sesquiterpenes, veranisatins D and E (5 and 6), and a new
      phenylpropane glycoside, oligandrumin E (7), were isolated from the ethanol
      extract of pericarps of Illicium oligandrum, together with six known
      sesquiterpenoids and two phenylpropanoids. Their structures were established on
      the basis of extensive spectroscopic analyses. The structures of 1 and 2 were
      further confirmed by single-crystal X-ray diffraction experiments. Anislactone B
      (13) and the erythro form of anethole glycol (14) were shown to attenuate the
      damage induced by H(2)O(2) in SH-SY5Y cells.

PMID- 19159274
TI  - Glionitrin A, an antibiotic-antitumor metabolite derived from competitive
      interaction between abandoned mine microbes.
AB  - The nutrient conditions present in abandoned coal mine drainages create an
      extreme environment where defensive and offensive microbial interactions could be
      critical for survival and fitness. Coculture of a mine drainage-derived
      Sphingomonas bacterial strain, KMK-001, and a mine drainage-derived Aspergillus
      fumigatus fungal strain, KMC-901, resulted in isolation of a new diketopiperazine
      disulfide, glionitrin A (1). Compound 1 was not detected in monoculture broths of
      KMK-001 or KMC-901. The structure of 1, a (3S,10aS) diketopiperazine disulfide
      containing a nitro aromatic ring, was based on analysis of MS, NMR, and circular
      dichroism spectra and confirmed by X-ray crystal data. Glionitrin A displayed
      significant antibiotic activity against a series of microbes including
      methicillin-resistant Staphylococcus aureus. An in vitro MTT cytotoxicity assay
      revealed that 1 had potent submicromolar cytotoxic activity against four human
      cancer cell lines: HCT-116, A549, AGS, and DU145. The results provide further
      evidence that microbial coculture can produce novel biologically relevant
      molecules.

PMID- 19159275
TI  - Rapid, general access to chiral beta-fluoroamines and beta,beta-difluoroamines
      via organocatalysis.
AB  - A rapid, general route to enantiopure beta-fluoroamines and beta,beta
      difluoroamines has been developed employing organocatalysis in both a two-pot and
      a one-pot procedure. Both chemical yields (64-82%) and enantioselectivity (94-98%
      ee) were excellent and represent a significant improvement in the art of
      preparing chemically diverse beta-fluoroamines from readily available precursors.

PMID- 19159276
TI  - Asymmetric synthesis of tetrahydroquinolin-3-ols via CoCl2-catalyzed reductive
      cyclization of nitro cyclic sulfites with NaBH4.
AB  - A new method for the construction of chiral 3-substituted tetrahydroquinoline
      derivatives based on asymmetric dihydroxylation and CoCl(2)-catalyzed reductive
      cyclization of nitro cyclic sulfites with NaBH(4) has been described with high
      optical purities. This method has been successfully applied in the formal
      synthesis of PNU 95666E and anachelin H chromophore.

PMID- 19159277
TI  - The marine sponge Diacarnus bismarckensis as a source of peroxiterpene inhibitors
      of Trypanosoma brucei, the causative agent of sleeping sickness.
AB  - Human African trypanosomiasis, also known as African sleeping sickness, is a
      neglected tropical disease with inadequate therapeutic options. We have launched
      a collaborative new lead discovery venture using our repository of extracts and
      natural product compounds as input into our growth inhibition primary screen
      against Trypanosoma brucei. Careful evaluation of the spectral data of the
      natural products and derivatives allowed for the elucidation of the absolute
      configuration (using the modified Mosher's method) of two new peroxiterpenes: (+)
      muqubilone B (1a) and (-)-ent-muqubilone (3a). Five known compounds were also
      isolated: (+)-sigmosceptrellin A (4a), (+)-sigmosceptrellin A methyl ester (4b),
      (-)-sigmosceptrellin B (5), (+)-epi-muqubillin A (6), and (-)-epi-nuapapuin B
      methyl ester (7). The isolated peroxiterpenes demonstrated activities in the
      range IC(50) = 0.2-2 mug/mL.

PMID- 19159278
TI  - Advanced substrate fabrication for cell microarrays.
AB  - The fabrication and characterization of chemical patterns using a technique that
      can be readily integrated with methods currently used for the formation of
      microarrays is presented. A high density poly(ethylene glycol) coating was
      deposited on glass slides as a background exhibiting low cell attachment
      properties. Phenylazide modified polymers were then printed on this background.
      UV irradiation of these polymer arrays resulted in the cross-linking of the
      polymer spots and their covalent attachment to the surface. Cell attachment was
      shown to follow the resultant surface chemistry pattern. Furthermore, the use of
      a robotic contact printer enabled the facile deposition of DNA microarrays on top
      of and aligned with the polymer microarrays. A transfected cell microarray was
      generated in this way, demonstrating not only the ability of this platform to
      limit cell attachment to specific regions, but the suitability for chip-based
      functional genomics, in particular, and high density cell assays in general.

PMID- 19159279
TI  - Improving the signal-to-noise performance of molecular diagnostics with PEG
      lysine copolymer dendrons.
AB  - The synthesis, characterization, and use of dendron-like poly(ethylene glycol)
      lysine (PEG-Lys) copolymers as an intermediate layer for biomolecular diagnostic
      signal enhancement is presented. Solid phase Fmoc-peptide synthesis was used to
      synthesize polymers with one, two, and three PEG-Lys comonomer units in both a
      linear and first and second-generation dendronic structure directly onto
      organosilica microspheres. The microsphere surface loadings (number of free amine
      sites) were modified and quantified through an innovative use of the protecting
      groups of coupled amino acids. Surfaces with 0.1-100% of the original loading
      corresponding to 0.3-270 nmol/m2 of free amines were achieved. The influence of
      polymer structure and surface loading (grafting density) on the signal-to-noise
      of the microsphere-based molecular diagnostic was assessed measuring the
      difference in the signal of a model protease digestion assay and reduction in the
      nonspecific adsorption of bovine serum albumin. Increasing the polymer grafting
      density and the addition of dendronic branching were both found to increase the
      assay signal and reduce the nonspecific protein adsorption.

PMID- 19159280
TI  - Heat stabilization of the tissue proteome: a new technology for improved
      proteomics.
AB  - After tissue or body fluid sampling, proteases and other protein-modifying
      enzymes can rapidly change composition of the proteome. As a direct consequence,
      analytical results will reflect a mix of in vivo proteome and ex vivo degradation
      products. Vital information about the presampling state may be destroyed or
      distorted, leading to variation between samples and incorrect conclusions. Sample
      stabilization and standardization of sample handling can reduce or eliminate this
      problem. Here, a novel tissue stabilization system which utilizes a combination
      of heat and pressure under vacuum was used to stop degradation in mouse brain
      tissue immediately after sampling. It was found by biochemical assays that
      enzymatic activity was reduced to background levels in stabilized samples.
      Western blot analysis confirmed that post-translational phosphorylations of
      analyzed proteins were stable and conserved for up to 2 h at room temperature and
      that peptide extracts were devoid of abundant protein degradation fragments. The
      combination of reduced complexity and proteolytic inactivation enabled mass
      spectrometric identification of several neuropeptides and endogenous peptides
      including modified species at higher levels compared to nonstabilized samples.
      The tissue stabilizing system ensures reproducible and rapid inactivation of
      enzymes. Therefore, the system provides a powerful improvement to proteomics by
      greatly reducing the complexity and dynamic range of the proteome in tissue
      samples and enables enhanced possibilities for discovery and analysis of
      clinically relevant protein/peptide biomarkers.

PMID- 19159281
TI  - Detection of metabolic alterations in non-tumor gastrointestinal tissue of the
      Apc(Min/+) mouse by (1)H MAS NMR spectroscopy.
AB  - In this study, we have used metabolic profiling (metabolomics/metabonomics) via
      high resolution magic angle spinning (HRMAS) and solution state (1)H NMR
      spectroscopy to characterize small bowel and colon tissue from the Apc(Min/+)
      mouse model of early gastrointestinal (GI) tumorigenesis. Multivariate analysis
      indicated the presence of metabolic differences between the morphologically
      normal/non-tumor tissue from approximately 10 week-old Apc(Min/+) mice and their
      wild-type litter mates. The metabolic profile of isolated lamina propria and
      epithelial cells from the same groups could also be discriminated on the basis of
      genotype. Accounting for systematic variation in individual metabolite levels
      across different anatomical regions of the lower GI tract, the metabolic
      phenotype of Apc(Min/+) lamina propria tissue was defined by significant
      increases in the phosphocholine/glycerophosphocholine ratio (PC/GPC, +21%) and
      decreases in GPC (-25%) and the gut-microbial cometabolite dimethylamine (DMA, 
      40%) relative to wild type. In the whole tissue, elevated lactate (+15%) and myo
      inositol (+19%) levels were detected. As the metabolic changes occurred in non
      tumor tissue from animals of very low tumor burden (<2 polyps/animal), they are
      likely to represent the specific consequence of reduced Apc function and very
      early events in tumorigenesis. The observed increase in PC/GPC ratio has been
      previously reported with immortalisation and malignant transformation of cells
      and is consistent with the role of Apc as a tumor suppressor. Phospholipase A2,
      which hydrolyses phosphatidylcholine to Acyl-GPC, is a known modifier gene of the
      model phenotype (Mom1), and altered expression of choline phospholipid enzymes
      has been reported in gut tissue from Apc(Min/+) mice. These results indicate the
      presence of a metabolic phenotype associated with "field cancerization",
      highlighting potential biomarkers for monitoring disease progression, for early
      evaluation of response to chemoprevention, and for predicting the severity of the
      polyposis phenotype in the Apc(Min/+) model.

PMID- 19159282
TI  - Hamster zona pellucida is formed by four glycoproteins: ZP1, ZP2, ZP3, and ZP4.
AB  - The zona pellucida (ZP) is an extracellular glycoprotein matrix that surrounds
      all mammalian oocytes. Recent data have shown the presence of four glycoproteins
      (ZP1, ZP2, ZP3, and ZP4) in the ZP of human and rat rather than the three
      glycoproteins proposed in the mouse model. In the hamster (Mesocricetus auratus),
      it was previously described that ZP was composed of three different
      glycoproteins, called ZP1, ZP2, and ZP3, even though only ZP2 and ZP3 have been
      cloned thus far. The aim of the study was to determine whether hamster might also
      express four, rather than three, ZP proteins. The full-length cDNAs encoding
      hamster ZP glycoproteins 1 and 4 were isolated using rapid amplification cDNA
      ends (RACE). The cDNA of ZP1 contains an open reading frame of 1851 nucleotides
      encoding a polypeptide of 616 amino acid residues. The amino acid sequence of ZP1
      revealed a high homology with other mammalian species like human (66%), rat
      (80%), and mouse (80%). The cDNA of ZP4 contains an open reading frame of 1632
      nucleotides encoding a polypeptide of 543 amino acid residues. The deduced amino
      acid sequence of ZP4 revealed high overall homology with rat (82%) and human
      (78%). Subsequent mass spectrometric analysis of the hamster ZP allowed
      identification of peptides from all four glycoproteins. The data presented in
      this study provide evidence, for the first time, that the hamster ZP matrix is
      composed of four glycoproteins.

PMID- 19159283
TI  - Array MAPPIT: high-throughput interactome analysis in mammalian cells.
AB  - Physical interactions between proteins play a key role in probably every cellular
      process. Efforts to chart the protein interaction networks are ongoing in a
      number of model organisms using a diversity of approaches. The resulting genome
      wide interaction maps will provide a scaffold for further detailed functional
      analysis. We developed MAPPIT, a mammalian two-hybrid approach that allows
      identification and analysis of mammalian protein-protein interactions in their
      native environment. Here, we introduce an efficient MAPPIT assay that permits
      high-throughput screening of arrayed collections of proteins and complements a
      previously published cDNA library screening approach. We validated both methods
      in screens for interaction partners of the Cullin-based E3 ubiquitin ligase
      subunits SKP1 and Elongin C. In addition to a number of known interactors, novel
      SKP1 and Elongin C binding proteins were identified. The array assay is an
      important addition to the MAPPIT suite of technologies that is expected to
      significantly increase its utility as a toolbox to screen for novel interactors
      of proteins or small molecules.

PMID- 19159285
TI  - Controlling HBV replication in vivo by intravenous administration of triggered
      PEGylated siRNA-nanoparticles.
AB  - Harnessing RNA interference (RNAi) to inhibit hepatitis B virus (HBV) gene
      expression has promising application to therapy. Here we describe a new
      hepatotropic nontoxic lipid-based vector system that is used to deliver
      chemically unmodified small interfering RNA (siRNA) sequences to the liver. Anti
      HBV formulations were generated by condensation of siRNA (A component) with
      cationic liposomes (B component) to form AB core particles. These core particles
      incorporate an aminoxy cholesteryl lipid for convenient surface postcoupling of
      polyethylene glycol (PEG; C component, stealth/biocompatibility polymer) to give
      triggered PEGylated siRNA-nanoparticles (also known as siRNA-ABC nanoparticles)
      with uniform small sizes of 80-100 nm in diameter. The oxime linkage that results
      from PEG coupling is pH sensitive and was included to facilitate acidic pH
      triggered release of nucleic acids from endosomes. Nanoparticle-mediated siRNA
      delivery results in HBV replication knockdown in cell culture and in murine
      hydrodynamic injection models in vivo. Furthermore repeated systemic
      administration of triggered PEGylated siRNA-nanoparticles to HBV transgenic mice
      results in the suppression of markers of HBV replication by up to 3-fold relative
      to controls over a 28 day period. This compares favorably to silencing effects
      seen during lamivudine treatment. Collectively these observations indicate that
      our PEGylated siRNA-nanoparticles may have valuable applications in RNAi-based
      HBV therapy.

PMID- 19159287
TI  - Single conical nanopores displaying pH-tunable rectifying characteristics.
      manipulating ionic transport with zwitterionic polymer brushes.
AB  - In this work we describe for the first time the integration of "smart" polymer
      brushes into single conical nanopores to obtain a new highly functional signal
      responsive chemical nanodevice. The responsive brushes were constituted of
      zwitterionic monomers whose charge is regulated via pH changes in the
      environmental conditions. The pH-dependent chemical equilibrium of the monomer
      units provides a fine-tuning of the ionic transport though the nanopore by simply
      presetting the pH of the electrolyte solution. Our results demonstrate that this
      strategy enables a higher degree of control over the rectification properties
      when compared to the nanochannels modified with charged monolayer assemblies. We
      envision that these results will create completely new avenues to build-up
      "smart" nanodevices using responsive polymer brushes integrated into single
      conical nanopores.

PMID- 19159286
TI  - Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active
      agonist of the farnesoid X receptor (FXR).
AB  - Azepino[4,5-b]indoles have been identified as potent agonists of the farnesoid X
      receptor (FXR). In vitro and in vivo optimization has led to the discovery of 6m
      (XL335, WAY-362450) as a potent, selective, and orally bioavailable FXR agonist
      (EC(50) = 4 nM, Eff = 149%). Oral administration of 6m to LDLR(-/-) mice results
      in lowering of cholesterol and triglycerides. Chronic administration in an
      atherosclerosis model results in significant reduction in aortic arch lesions.

PMID- 19159288
TI  - Element lines: bonding in the ternary gold polyphosphides, Au(2)MP(2) with M =
      Pb, Tl, or Hg.
AB  - We present a theoretical study of the electronic structures of Au(2)PbP(2),
      Au(2)TlP(2), and Au(2)HgP(2). Structurally, these compounds contain a framework
      of condensed Au(2)P(6) and Au(4)P(6) rings forming parallel channels, which are
      filled by lead, thallium, or mercury atoms. Given the linear coordination of the
      Au atoms and the existence of zigzag -[P-P-P]- singly-bonded chains in them,
      these materials present us with a rare instance of approximately linear, one
      dimensional, and zerovalent element (Pb, Tl, or Hg) chains with a variable
      electron count. The Pb-Pb, Tl-Tl, and Hg-Hg element lines in these structures
      have somewhat longer bond lengths than their respective single bond lengths or
      their separations in (calculated) isolated chains. Yet, the zerovalent element
      interactions are prominent and are responsible for the metallicity of some of
      these materials. In the calculations, both Au(2)PbP(2) and Au(2)TlP(2) emerge as
      metallic, whereas Au(2)HgP(2) is a semiconductor. The isolated element chains do
      not undergo a pairing (Peierls) distortion nor do the chains in the three
      dimensional ternaries. The small barrier for mobility of the Pb, Tl, and Hg atoms
      along the chain axis may explain the large thermal parameters observed in the
      crystal structures along the chain axis (and the need to use fractional
      occupations of several positions along the chain). These ternaries may show one
      dimensional liquidlike behavior under some conditions.

PMID- 19159289
TI  - Selective fluorogenic and chromogenic probe for detection of silver ions and
      silver nanoparticles in aqueous media.
AB  - A novel rhodamine-based fluorogenic and chromogenic probe for Ag(+) ions in
      aqueous media is developed, which can be also used for the detection of AgNPs.
      The sensing mechanism is based on irreversible tandem ring-opening and -forming
      processes promoted by Ag(+)-coordination to the iodide of the probe, which is
      accompanied by both color and turn-on type fluorescence changes. The probe shows
      remarkably high selectivity over other metal ions and detects silver ions up to
      14 ppb.

PMID- 19159290
TI  - Apo adenylate kinase encodes its holo form: a principal component and varimax
      analysis.
AB  - Adenylate kinase undergoes large-scale motions of its LID and AMP-binding (AMPbd)
      domains when its apo, open form closes over its substrates, AMP and Mg2+-ATP. It
      may be an example of an enzyme that provides an ensemble of conformations in its
      apo state from which its substrates can select and bind to produce catalytically
      competent conformations. In this work, the fluctuations of the enzyme apo
      Escherichia coli adenylate kinase (AKE) are obtained with molecular dynamics. The
      resulting trajectory is analyzed with principal component analysis (PCA) that
      decomposes the atom motions into orthogonal modes ordered by their decreasing
      contributions to the total protein fluctuation. In apo AKE, a small set of the
      PCA modes describes the bulk of the fluctuations. Identification of the atom
      motions that are important contributors to these modes is improved with the use
      of a varimax rotation method that rotates the PCA modes to a new mode set that
      concentrates the atom contributions to a smaller set of atoms in these new modes.
      In this way, the nature of the important motions of the LID and AMPbd domains are
      clarified. The dominant PCA modes are used to investigate if apo AKE can
      fluctuate to conformations that are holo-like, even though the apo trajectory is
      mainly confined to a region around the initial apo structure. This is
      accomplished by expressing the difference between the protein coordinates,
      obtained from the holo and apo crystal structures, using as a basis the PCA modes
      from the apo AKE trajectory. The coherent motion described by a small set of the
      apo PCA modes is shown to be able to produce protein conformations that are quite
      similar to the holo conformation of the protein. In this sense, apo AKE does
      encode in its fluctuations information about holo-like conformations.

PMID- 19159291
TI  - Interactions of a tetraanionic porphyrin with DNA: from a Z-DNA sensor to a
      versatile supramolecular device.
AB  - The anionic nickel(II) porphyrin NiTPPS is able to selectively sense the spermine
      induced left-handed Z-form of DNA while it is completely silent in the presence
      of right-handed B-DNA. Interactions between the DNA and the porphyrin can be
      easily modulated by pH and temperature. The resulting Z-DNA-porphyrin-spermine
      complex behaves as a supramolecular reversible information storage system and as
      a reversible AND logic gate.

PMID- 19159292
TI  - A secondary kinetic isotope effect study of the 1-deoxy-D-xylulose-5-phosphate
      reductoisomerase-catalyzed reaction: evidence for a retroaldol-aldol
      rearrangement.
AB  - 1-Deoxy-d-xylulose 5-phosphate (DXP) reductoisomerase (DXR, also known as methyl
      d-erythritol 4-phosphate (MEP) synthase) is a NADPH-dependent enzyme, which
      catalyzes the conversion of DXP to MEP in the nonmevalonate pathway of isoprene
      biosynthesis. Two mechanisms have been proposed for the DXR-catalyzed reaction.
      In the alpha-ketol rearrangement mechanism, the reaction begins with
      deprotonation of the C-3 hydroxyl group followed by a 1,2-migration to give
      methylerythrose phosphate, which is then reduced to MEP by NADPH. In the
      retroaldol/aldol rearrangement mechanism, DXR first cleaves the C3-C4 bond of DXP
      in a retroaldol manner to generate a three-carbon and a two-carbon phosphate
      bimolecular intermediate. These two species are then reunited by an aldol
      reaction to form a new C-C bond, yielding an aldehyde intermediate. Subsequent
      reduction by NADPH affords MEP. To differentiate these mechanisms, we have
      prepared [3-(2)H]- and [4-(2)H]-DXP and carried out a competitive secondary
      kinetic isotope effect (KIE) study of the DXR reaction. The normal 2 degrees KIEs
      observed for [3-(2)H]- and [4-(2)H]-DXP provide compelling evidence supporting a
      retroaldol/aldol mechanism for the rearrangement catalyzed by DXR, with the rate
      limiting step being cleavage of the C3-C4 bond of DXP.

PMID- 19159293
TI  - Versatile cyclic templates for assembly of axially oriented ligands.
AB  - In this paper, we describe two novel types of planar cyclic peptide templates for
      the facile addition of ligands that extend axially from the plane of the template
      ring. The first uses beta-amino acids of alternating D- and L-chirality, since
      the insertion of the additional methylene group in the peptide backbone was
      predicted and subsequently shown by NMR and molecular modeling, to reorient
      ligands attached to amino acid side chain axially with respect to the template
      ring. A second contains alternating D- and L-amino acids with an achiral Gly
      residue interposed between each chiral amino acid. The inserted Gly residues also
      tend to reorient side chains axially rather than radially, as was demonstrated by
      NMR and molecular modeling. The axial orientation of attached ligands is intended
      to foster or allow interactions among attached ligands in situations in which
      this is desired. Two such situations that we consider are (1) development of
      immunological reagents with avidity effects and (2) modeling of oligomers in
      fibril-forming peptides. Toward the first of these goals, we demonstrated that
      these templates are suitable for attaching macromolecules, by incorporating two
      types of protein, neutravidin and trypsinogen. Toward the second goal, we
      demonstrate the attachment of two different fibril-forming peptides to the
      template. The templates described herein thus have many of the desirable traits
      of such molecules, i.e., (1) multivalency for the attachment of multiple ligands,
      (2) suitable chemical functions for facile attachment of ligands, (3) versatility
      as to the number and spacing of ligand attachment sites, (4) sufficient rigidity
      so that the attached ligands can be similarly oriented with respect to the
      template, and (5) sufficient flexibility to allow even large ligands, such as
      proteins, to attach and interact.

PMID- 19159295
TI  - Metal-catalyst-free growth of single-walled carbon nanotubes on substrates.
AB  - In this communication, we have demonstrated that SiO(2) nanoparticles can be
      generated by simply scratching the quartz or silicon wafer with a SiO(2) layer
      and confirmed it to be active for the growth of SWNTs for the first time.
      Furthermore, the SWNTs from SiO(2) has a much narrower size distribution. This
      may open a way to control the diameter of the SWNTs. More importantly, our work
      has found a series of oxides including Al(2)O(3), TiO(2), and rare earth oxides
      to be active for SWNT growth as well. These findings not only provide an
      alternative new type of catalysts for the growth of SWNTs but also give more
      insight into the role of the catalysts and a deeper understanding of the growth
      mechanism of SWNTs. The effective catalysts and catalytic activity for SWNT
      growth seem to be more size-dependent than the catalysts. Long oriented SWNTs
      generated from these catalysts enable us to rule out the relationship between the
      catalysts and the structures of the SWNTs. Thus controlled growth of SWNTs
      including the diameter and chirality is expected to be eventually realized.

PMID- 19159294
TI  - Cationic nucleoside lipids based on a 3-nitropyrrole universal base for siRNA
      delivery.
AB  - Cationic nucleoside lipids based on a 3-nitropyrrole universal base were prepared
      from D-ribose using a straightforward chemical synthesis. Several studies
      including DLS, TEM, and ethidium bromide (EthBr) assay demonstrated that these
      amphiphilic molecules form supramolecular organizations of nanometer size in
      aqueous solutions and are able to bind nucleic acids. siRNA knockdown experiments
      were performed with these nucleolipids, and we observed protein knockdown
      activity similar to the siPORT NeoFX positive control. No significant
      cytotoxicity was found.

PMID- 19159296
TI  - Adsorption-desorption induced structural changes of Cu-MOF evidenced by solid
      state NMR and EPR spectroscopy.
AB  - Adsorption-desorption induced structural changes of
      Cu(bpy)(H(2)O)(2)(BF(4)),(bpy) (bpy = 4,4'-bipyridine) [Cu-MOF] have been
      evidenced by combined NMR and EPR spectroscopy. Upon adsorption of probe
      molecules even at a few mbar, EPR spectra show that they are activated to form
      complexes at Cu(II) sites, which results in a change of the Cu-MOF's structure as
      indicated by a high-field shift of the (11)B MAS NMR. After desorption, both EPR
      and (11)B MAS NMR spectra evidenced that the structure of the Cu-MOF reversibly
      shifted to the original state. This observation indicates that MOFs can undergo
      structural changes during processes where adsorption-desorption steps are
      involved such as gas storage, separation, and catalysis.

PMID- 19159297
TI  - Tightly connected water wires facilitate fast proton uptake at the proton
      entrance of proton pumping proteins.
AB  - Tightly connected water wires (TCW) exist in systems with nonconfined water like
      the solvated membrane proton pump system. The TCWs that connect to the negatively
      charged proton entrance facilitate the fast proton uptake of the proton pump.
      They function as a direct proton bridge or/and stabilizer of protons within the
      Coulomb cage of the proton entrance. Negatively charged residue(s) at the proton
      entrance induce a large population of long TCWs. Additional negatively charged
      residues increase the population of such long TCWs and, thus, raise the
      possibility to capture proton from the solution.

PMID- 19159298
TI  - High capacity hydrogen adsorption in Cu(II) tetracarboxylate framework materials:
      the role of pore size, ligand functionalization, and exposed metal sites.
AB  - A series of isostructural metal-organic framework polymers of composition
      [Cu2(L)(H2O)2] (L= tetracarboxylate ligands), denoted NOTT-nnn, has been
      synthesized and characterized. Single crystal X-ray structures confirm the
      complexes to contain binuclear Cu(II) paddlewheel nodes each bridged by four
      carboxylate centers to give a NbO-type network of 64.82 topology. These complexes
      are activated by solvent exchange with acetone coupled to heating cycles under
      vacuum to afford the desolvated porous materials NOTT-100 to NOTT-109. These
      incorporate a vacant coordination site at each Cu(II) center and have large pore
      volumes that contribute to the observed high H2 adsorption. Indeed, NOTT-103 at
      77 K and 60 bar shows a very high total H2 adsorption of 77.8 mg g(-)- equivalent
      to 7.78 wt% [wt% = (weight of adsorbed H2)/(weight of host material)] or 7.22 wt%
      [wt% = 100(weight of adsorbed H2)/(weight of host material + weight of adsorbed
      H2)]. Neutron powder diffraction studies on NOTT-101 reveal three adsorption
      sites for this material: at the exposed Cu(II) coordination site, at the pocket
      formed by three {Cu2} paddle wheels, and at the cusp of three phenyl rings.
      Systematic virial analysis of the H2 isotherms suggests that the H2 binding
      energies at these sites are very similar and the differences are smaller than 1.0
      kJ mol-1, although the adsorption enthalpies for H2 at the exposed Cu(II) site
      are significantly affected by pore metrics. Introducing methyl groups or using
      kinked ligands to create smaller pores can enhance the isosteric heat of
      adsorption and improve H2 adsorption. However, although increasing the overlap of
      potential energy fields of pore walls increases the heat of H2 adsorption at low
      pressure, it may be detrimental to the overall adsorption capacity by reducing
      the pore volume.

PMID- 19159299
TI  - Highly fluorescent rigid supramolecular polymeric nanowires constructed through
      multiple hydrogen bonds.
AB  - Supramolecular polymeric nanowires 1(n) constructed by a 3D shape-persistent
      hexaacid 1 through multiple hydrogen bonding interactions was developed. Single
      molecular nanoires were also obtained from its highly dilute solution.Hexaacid 1
      containing pi-conjugated chromophores successfully self-assembled to afford these
      nanofibers with high solid quantum efficiency (22%), which provides us a pathway
      to fabricate optoelectronic devices using these highly fluorescent nanofibers.

PMID- 19159301
TI  - Differential protein mapping of ovarian serous adenocarcinomas: identification of
      potential markers for distinct tumor stage.
AB  - Ovarian serous carcinomas (OSCs) comprise over half of all ovarian carcinomas and
      account for the majority of ovarian cancer-related deaths. We used a 2
      dimensional liquid-based protein mapping strategy to characterize global protein
      expression patterns in 19 OSC tumor samples from 15 different patients to
      facilitate molecular classification of tumor stage. Protein expression profiles
      were produced, using pI-based separation in the first dimension and
      hydrophobicity-based separation in the second dimension, over a pH range of 4.0
      7.0. Hierarchical clustering was applied to protein maps to indicate the tumor
      interrelationships. The 19 tumor samples could be classified into two different
      groups, one group associated with low stage (Stage 1) tumors and the other group
      associated with high stage (Stages 3/4) tumors. Proteins that were differentially
      expressed in different groups were selected for identification by LTQ-ESI-MS/MS.
      Fourteen of the selected proteins were overexpressed in the low stage tumors; 46
      of the proteins were overexpressed in the high stage tumors. These proteins are
      known to play an important role in cellular functions such as glycolysis, protein
      biosynthesis, and cytoskeleton rearrangement and may serve as markers associated
      with different stages of OSCs. To further confirm the stage-dependent protein
      identifications, Lamin A/C and Vimentin expression in ovarian serous carcinomas
      was assessed by immunohistochemistry using ovarian tumor tissue microarrays for
      66 samples.

PMID- 19159302
TI  - Anthocyanin composition and oxygen radical scavenging capacity (ORAC) of milled
      and pearled purple, black, and common barley.
AB  - The importance of anthocyanins to the total antioxidant capacity of various
      fruits and vegetables has been well established, but less attention has been
      focused on cereal grains. This study investigated the antioxidant capacity and
      anthocyanin composition of a bran-rich pearling fraction (10% outer kernel
      layers) and whole kernel flour of purple (CI-1248), black (PERU-35), and yellow
      (EX-83) barley genotypes. HPLC analysis showed that as much as 6 times more
      anthocyanin per unit weight (microg/g) was present in the bran-rich fractions of
      yellow and purple barley (1587 and 3534, respectively) than in their
      corresponding whole kernel flours (210 and 573, respectively). Delphinidin 3
      glucoside, delphinidin 3-rutinoside, cyanidin 3-glucoside, petunidin 3-glucoside,
      and cyanidin chloride were positively identified in barley, with as many as 9 and
      15 anthocyanins being detected in yellow and purple barley, respectively.
      Antioxidant activity analysis showed that the ORAC values for the bran-rich
      fractions were significantly (p < 0.05) higher than for the whole kernel flour.

PMID- 19159303
TI  - Spectroscopic studies of the light-color modulation mechanism of firefly (beetle)
      bioluminescence.
AB  - To reveal the light-color modulation mechanism of firefly (beetle)
      bioluminescence, we investigated the spectroscopic properties of the phenolate
      anion 1-O(-) generated from 5,5-dimethyloxyluciferin (1-OH) using various
      base/solvent combinations. Phenolate anion 1-O(-) is a model compound for the
      keto form of wild-type oxyluciferin phenolate anion (OL(-)), which is postulated
      to be the emitter of the bioluminescence. The fluorescence maxima of 1-O(-) were
      found to depend on the base/solvent combination used, and they varied in the
      range 541-640 nm, which covers the almost whole range of the bioluminescence
      emission maximum. In a polar solvent, where (1)(1-O(-))* and the countercation
      (the conjugate acid of a base) make a solvent-separated ion pair or a free ion
      couple, the emission maxima of 1-O(-) were found to be modulated by the solvent
      polarity. In a less polar solvent, where (1)(1-O(-))* and the countercation are
      formed as a contact ion pair, the strength of the covalent character of the
      O8'...H bond between (1)(1-O(-))* and the countercation is operative. The effect
      of the base/solvent combination on the emission properties of (1)(1-O(-))* was
      also verified using fluorescence lifetime measurements and density functional
      theory calculations on 1-O(-) and its ion-pair models. On the basis of these
      results, we propose the following light-color modulation mechanism: (1) the light
      emitter is the excited singlet state of OL(-) [(1)(OL(-))*], and (2) light
      emission from (1)(OL(-))* is modulated by the polarity of the active-site
      environment of a luciferase and the degree of covalent character of the O8'...H
      bond between (1)(OL(-))* and a protonated basic moiety in the active site.
      Mechanisms for variation of the bioluminescence colors and their applications are
      discussed.

PMID- 19159304
TI  - Implications of pathogenesis by Erwinia amylovora on rosaceous stigmas to
      biological control of fire blight.
AB  - As a prerequisite to infection of flowers, Erwinia amylovora grows epiphytically
      on stigmas, which provide a conducive habitat for bacterial growth. Stigmas also
      support growth of several other bacterial genera, which allows for biological
      control of fire blight; although, in practice, it is very difficult to exclude E.
      amylovora completely from this habitat. We investigated the dynamics of growth
      suppression of E. amylovora by comparing the ability of virulent and avirulent
      strains of E. amylovora to compete with each other on stigmas of pear, apple, and
      blackberry, and to compete with a co-inoculated mixture of effective bacterial
      antagonists. When strains were inoculated individually, virulent E. amylovora
      strain Ea153N attained the highest population size on stigmas, with population
      sizes that were approximately double those of an avirulent hrpL mutant of Ea153
      or the bacterial antagonists. In competition experiments, growth of the avirulent
      derivative was suppressed by the antagonist mixture to a greater extent than the
      virulent strain. Unexpectedly, the virulent strain enhanced the population size
      of the antagonist mixture. Similarly, a small dose of virulent Ea153N added to
      inoculum of an avirulent hrpL mutant of Ea153 significantly increased the
      population size of the avirulent strain. A pathogenesis-gene reporter strain,
      Ea153 dspE::gfp, was applied to flowers and a subset of the population expressed
      the green fluorescent protein while growing epiphytically on stigmas of apple.
      These results are consistent with the hypothesis that virulent E. amylovora
      modifies the epiphytic habitat presented by the stigma through a pathogenesis
      related process, which increases host resources available to itself and,
      coincidentally, to nonpathogenic competitors. Over nine orchard trials, avirulent
      Ea153 hrpL significantly suppressed the incidence of fire blight four times
      compared with six for the antagonist mixture. The degree of biological control
      achievable with an avirulent strain of E. amylovora likely is limited by its
      inability to utilize the stigmatic habitat to the same degree as a virulent
      strain.

PMID- 19159305
TI  - Quantitative distribution of 'Candidatus Liberibacter asiaticus' in citrus plants
      with citrus huanglongbing.
AB  - Citrus huanglongbing (HLB), or greening disease, is strongly associated with any
      of three nonculturable gram-negative bacteria belonging to 'Candidatus
      Liberibacter spp.' 'Ca. Liberibacter spp.' are transmitted by citrus psyllids to
      all commercial cultivars of citrus. The diseases can be lethal to citrus and have
      recently become widespread in both Sao Paulo, Brazil, and Florida, United States,
      the locations of the largest citrus industries in the world. Asiatic HLB, the
      form of the disease found in Florida, is associated with 'Ca. Liberibacter
      asiaticus' and is the subject of this report. The nonculturable nature of the
      pathogen has hampered research and little is known about the distribution of 'Ca.
      L. asiaticus' in infected trees. In this study, we have used a quantitative
      polymerase chain reaction assay to systematically quantify the distribution of
      'Ca. L. asiaticus' genomes in tissues of six species of citrus either identified
      in the field during survey efforts in Florida or propagated in a greenhouse in
      Beltsville, MD. The populations of 'Ca. L. asiaticus' inferred from the
      distribution of 16S rDNA sequences specific for 'Ca. L. asiaticus' in leaf
      midribs, leaf blades, and bark samples varied by a factor of 1,000 among samples
      prepared from the six citrus species tested and by a factor of 100 between two
      sweet orange trees tested. In naturally infected trees, above-ground portions of
      the tree averaged 10(10) 'Ca. L. asiaticus' genomes per gram of tissue. Similar
      levels of 'Ca. L. asiaticus' genomes were observed in some but not all root
      samples from the same plants. In samples taken from greenhouse-inoculated trees,
      levels of 'Ca. L. asiaticus' genomes varied systematically from 10(4) genomes/g
      at the graft inoculation site to 10(10) genomes/g in some leaf petioles. Root
      samples from these trees also contained 'Ca. L. asiaticus' at 10(7) genomes/g. In
      symptomatic fruit tissues, 'Ca. L. asiaticus' genomes were also readily detected
      and quantified. The highest levels of 'Ca. L. asiaticus' in fruit tissues were
      found in the locular membranes and septa (10(8) genomes/g), with 100-fold lower
      levels of 'Ca. L. asiaticus' in the meso and pericarp of such fruit. Our results
      demonstrate both the ubiquitous presence of 'Ca. L. asiaticus' in symptomatic
      citrus trees as well as great variation between individual trees and among
      samples of different tissues from the same trees. Our methods will be useful in
      both the management and scientific study of citrus HLB, also known as citrus
      greening disease.

PMID- 19159306
TI  - Genetic loci involved in rubrifacine production in the walnut pathogen Brenneria
      rubrifaciens.
AB  - Brenneria rubrifaciens produces a unique red pigment known as rubrifacine that
      has been hypothesized to play a role in pathogenesis on walnut. Analysis of DNA
      flanking the Tn5 insertion site in 20 rubrifacine minus (pig(-)) mutants
      identified three regions required for rubrifacine production. The first region
      was homologous to nonribosomal peptide synthetases (NRPS), the second was
      homologous to autoinducer synthase genes (expI homologs), and the third region
      was homologous to the slyA gene of Candidatus blochmania and Escherichia coli.
      Pigment production was not necessary for elicitation of the hypersensitive
      response (HR) in tobacco and had little impact on virulence in tissue-cultured
      walnut plants. The expI-interrupted mutants exhibited reduced virulence on walnut
      and were HR negative on tobacco. Pigment production was restored in Br-212 when
      grown in the presence of wild-type B. rubrifaciens, E. coli carrying the cloned
      expI-like gene, or introduction of the cloned wild-type copy of the expI-like
      gene. Two Brenneria spp., B. nigrifluens and B. salicis, also restored pigment
      production in Br-212. These results demonstrate that rubrifacine production and
      virulence of B. rubrifaciens on walnut are under the control of a quorum-sensing
      system and are sensitive to signal molecules from other Brenneria spp.

PMID- 19159307
TI  - Interaction of the mite Aceria mangiferae with Fusarium mangiferae, the causal
      agent of mango malformation disease.
AB  - The role of the mango bud mite, Aceria mangiferae, in carrying conidia of
      Fusarium mangiferae, vectoring them into potential infection sites, and assisting
      fungal infection and dissemination was studied. Following the mite's exposure to
      a green fluorescent protein-marked isolate, conidia were observed clinging to the
      mite's body. Agar plugs bearing either bud mites or the pathogen were placed on
      leaves near the apical buds of potted mango plants. Conidia were found in bud
      bracts only when both mites and conidia were co-inoculated on the plant,
      demonstrating that the mite vectored the conidia into the apical bud. Potted
      mango plants were inoculated with conidia in the presence or absence of mites.
      Frequency and severity of infected buds were significantly higher in the presence
      of mites, revealing their significant role in the fungal infection process.
      Conidia and mite presence were monitored with traps in a diseased orchard over a
      2-year period. No windborne bud mites bearing conidia were found; however, high
      numbers of windborne conidia were detected in the traps. These results suggest
      that A. mangiferae can carry and vector conidia between buds and assist in fungal
      penetration but does not play a role in the aerial dissemination of conidia
      between trees.

PMID- 19159308
TI  - Inoculum availability and conidial dispersal patterns of Fusarium mangiferae, the
      causal agent of mango malformation disease.
AB  - Inoculum availability and conidial dispersal patterns of Fusarium mangiferae,
      causal agent of mango malformation disease, were studied during 2006 and 2007 in
      an experimental orchard. The spatial pattern of primary infections in a heavily
      infected commercial mango orchard corresponded with a typical dispersal pattern
      caused by airborne propagules. Malformed inflorescences were first observed in
      mid-March, gradually increased, reaching a peak in May, and declined to
      negligible levels in August. The sporulation capacity of the malformed
      inflorescences was evaluated during three consecutive months. Significantly
      higher numbers of conidia per gram of malformed inflorescence were detected in
      May and June than in April. Annual conidial dissemination patterns were evaluated
      by active and passive trapping of conidia. A peak in trapped airborne conidia was
      detected in May and June for both years. The daily pattern of conidial dispersal
      was not associated with a specifically discernable time of day, and an
      exponential correlation was determined between mean relative humidity (RH) and
      mean number of trapped conidia. Higher numbers of conidia were trapped when RH
      values were low (<55%). This is the first detailed report on airborne dispersal
      of F. mangiferae, serving as the primary means of inoculum spread.

PMID- 19159309
TI  - Ultrastructural alterations in Fusarium sambucinum and Heterobasidion annosum
      treated with aluminum chloride and sodium metabisulfite.
AB  - Aluminum chloride (AlCl(3)) and sodium metabisulfite (Na(2)S(2)O(5)) have
      received increasing attention as antifungal agents for the control of plant
      diseases. In an effort to understand their toxic action on fungi, ultrastructural
      changes and membrane damage in Fusarium sambucinum (Ascomycota) and
      Heterobasidion annosum (Basidiomycota) in response to salt exposure was
      investigated using transmission electron microscopy. Conidial membrane damage was
      quantified using SYTOX Green stain, which only enters altered membranes. The
      results showed that mortality of the conidia was generally closely associated
      with SYTOX stain absorption in F. sambucinum treated with Na(2)S(2)O(5) and in H.
      annosum treated with AlCl(3) or Na(2)S(2)O(5), suggesting that these salts cause
      membrane alterations. For both fungi, ultrastructural alterations in conidia
      treated with AlCl(3) and Na(2)S(2)O(5) included membrane retraction, undulation,
      and invagination. At higher concentrations or exposure periods to the salts, loss
      of membrane integrity, cytoplasmic leakage, and cell rupture were observed.
      Ultrastructural alterations and increased SYTOX stain absorption in salt-treated
      conidia appear consistent with a mode of action where AlCl(3) and Na(2)S(2)O(5)
      alter membrane integrity and permeability.

PMID- 19159310
TI  - Real-time quantitative expression studies of the zearalenone biosynthetic gene
      cluster in Fusarium graminearum.
AB  - The estrogenic mycotoxin zearalenone (ZON) produced by some Fusarium spp. causes
      reproductive problems and hyperestrogenic syndromes in mammals. In an effort to
      elucidate the molecular pathways of ZON production, we present a comparative real
      time quantitative polymerase chain reaction expression study of seven contiguous
      genes in the ZON biosynthetic cluster on sterile rice and during wheat and oat
      infection. Under ZON production on rice, the polyketide synthase (PKS) genes PKS4
      and PKS13, alcohol oxidase FG12056 gene, and transcriptional regulator FG02398
      gene showed similarly upregulated patterns, whereas the nonribosomal peptide
      synthetase (NPS) FG02394, the K(+) channel beta subunit FG12015, and the protein
      kinase FG02399 displayed a variant pattern. During the same time period under
      wheat infection when no ZON was produced, the PKS genes and the NPS were
      downregulated relative to rice whereas the K(+) channel beta subunit gene FG12015
      was markedly upregulated, suggesting that it may play a role in the infection
      process. This is the first expression study of ZON biosynthetic genes in planta.
      The results give insight into the regulation and activities of the ZON gene
      cluster under different experimental systems and suggest a connection between ZON
      and a K(+) channel that could reveal a novel function for ZON in Fusarium spp.

PMID- 19159311
TI  - Rapid change in the genetic diversity of Botrytis cinerea populations after the
      introduction of strains in a tomato glasshouse.
AB  - In tomato glasshouses, the population structure of airborne inoculum of Botrytis
      cinerea depends on the production of endogenous inoculum on diseased plants as
      well as on incoming exogenous inoculum. Both types of inocula may contribute
      differently to the development of epidemics. Two strains of B. cinerea were
      introduced in each of four separate compartments of an experimental tomato
      glasshouse. We monitored their impact on disease development and on the genetic
      diversity of B. cinerea populations using microsatellite markers. The naturally
      occurring airborne inoculum of B. cinerea displayed a high level of genetic
      diversity and was rapidly displaced in the glasshouse, as isolates with
      microsatellite profiles identical to the introduced strains amounted to 66% of
      the inoculum sampled from the air 14 days after inoculation and 91% of those
      collected from stem lesions 60 days after inoculation. This suggested an
      important role of secondary inoculum in disease development, which is compatible
      with the hypothesis of a polycyclic development of gray mold epidemics in tomato
      glasshouses. In controlled-environment tests on tomatoes, a wide range of
      aggressiveness levels was observed, both for isolates sampled from the air and
      from lesions on plants. Hypotheses are proposed to explain the negligible impact
      of naturally incoming isolates on the epidemics observed inside the four
      glasshouse compartments.

PMID- 19159312
TI  - AER1, a major gene conferring resistance to Aphanomyces euteiches in Medicago
      truncatula.
AB  - Aphanomyces euteiches is a major soilborne oomycete pathogen that infects various
      legume species, including pea and alfalfa. The model legume Medicago truncatula
      has recently emerged as a valuable genetic system for understanding the genetic
      basis of resistance to A. euteiches in leguminous crops. The objective of this
      study was to identify genetic determinants of resistance to a broad host-range
      pea-infecting strain of A. euteiches in M. truncatula. Two M. truncatula
      segregating populations of 178 F(5) recombinant inbred lines and 200 F(3)
      families from the cross F83005.5 (susceptible) x DZA045.5 (resistant) were
      screened for resistance to A. euteiches. Phenotypic distributions observed
      suggested a dominant monogenic control of resistance. A major locus associated
      with resistance to A. euteiches, namely AER1, was mapped by bulk segregant
      analysis to a terminal end of chromosome 3 in M. truncatula and explained 88% of
      the phenotypic variation. AER1 was identified in a resistance-gene-rich region,
      where resistance gene analogs and genes associated with disease resistance
      phenotypes have been identified. Discovery of AER1 opens up new prospects for
      improving resistance to A. euteiches in cultivated legumes using a comparative
      genomics approach.

PMID- 19159313
TI  - Environmental control in tea fields to reduce infection by Pseudomonas syringae
      pv. theae.
AB  - Bacterial shoot blight (BSB) disease, caused by Pseudomonas syringae pv. theae,
      is a major bacterial disease of tea plants in Japan. BSB mainly occurs in the low
      temperature season, and lesion formation by P. syringae pv. theae is enhanced by
      both low temperature and the presence of ice nucleation-active Xanthomonas
      campestris (INAX), which catalyzes ice formation at -2 to -4 degrees C and is
      frequently co-isolated with P. syringae pv. theae from tea plants. Low
      temperature is thus the most important environmental factor influencing the
      incidence of BSB; however, the effects of low temperature on infection of the
      host by P. syringae pv. theae and of environmental controls in fields on the
      occurrence of the disease are poorly understood. In this study, we show that ice
      formation on tea leaves by INAX enhanced P. syringae pv. theae invasion into leaf
      tissue. The natural incidence of BSB in the field was closely related to early
      autumn frost. Frost protection in late autumn, which prevented ice formation on
      tea plants, significantly decreased the incidence of BSB, and frost protection
      combined with bactericide application held the incidence under the economic
      threshold level. Our data indicate that environmental control in the field based
      on microbial interactions in the host offers a new strategy for plant disease
      control.

PMID- 19159315
TI  - Autoxidation of platinum(IV) hydrocarbyl hydride complexes to form platinum(IV)
      hydrocarbyl hydroperoxide complexes.
AB  - The platinum(IV) hydride complexes Tp(Me(2))PtR(2)H (Tp(Me(2)) = hydridotris(3,5
      dimethylpyrazolyl)borate, R = Me (1a), Ph (1b)) react with molecular oxygen to
      form platinum(IV) hydroperoxide complexes Tp(Me(2))PtR(2)OOH (R = Me (2a) and Ph
      (2b), respectively) in high yield. The results of kinetic and mechanistic studies
      of these reactions are consistent with the net insertion of molecular oxygen into
      the Pt(IV)-H bonds occurring via radical chain mechanisms. The radical chain
      pathways resemble, in many respects, those documented for autoxidations of
      organic substrates, but significant differences are also evident. The
      autoxidations of 1a and 1b both autoaccelerate, but the nature of the rate
      accelerations and the dependence of the rates on the hydroperoxide products are
      not the same. The different rate laws observed for the reactions of
      Tp(Me(2))PtR(2)H complexes with molecular oxygen can be rationalized on the basis
      of similar initiation and propagation events with different chain termination
      steps.

PMID- 19159314
TI  - Campylobacter jejuni PglH is a single active site processive polymerase that
      utilizes product inhibition to limit sequential glycosyl transfer reactions.
AB  - Asparagine-linked protein glycosylation is essential for the virulence of the
      human gut mucosal pathogen Campylobacter jejuni . The heptasaccharide that is
      transferred to proteins is biosynthesized via the glycosyltransferase-catalyzed
      addition of sugar units to an undecaprenyl diphosphate-linked carrier. Genetic
      studies on the heptasaccharide assembly enzymes have shown that PglH, which
      transfers three terminal N-acetyl-galactosamine (GalNAc) residues to the carrier
      polyisoprene, is essential for chick colonization by C. jejuni . While it is now
      clear that PglH catalyzes multiple transfer reactions, the mechanism whereby the
      reactions cease after the addition of just three GalNAc residues has yet to be
      understood. To address this issue, a series of mechanistic biochemical studies
      was conducted with purified native PglH. This enzyme was found to follow a
      processive mechanism under initial rate conditions; however, product inhibition
      and product accumulation led to PglH release of intermediate products prior to
      complete conversion to the native ultimate product. Point mutations of an
      essential EX(7)E sequence motif were used to demonstrate that a single active
      site was responsible for all three transferase reactions, and a homology model
      with the mannosyltransferase PimA, from Mycobacteria smegmatis , establishes the
      requirement of the EX(7)E motif in catalysis. Finally, increased binding affinity
      with increasing glycan size is proposed to provide PglH with a counting mechanism
      that does not allow the transfer of more than three GalNAc residues. These
      results provide important mechanistic insights into the function of the glycosyl
      transfer polymerase that is related to the virulence of C. jejuni .

PMID- 19159316
TI  - Synthesis, characterization, and properties of organically templated lanthanide
      oxalatophosphates with a three-dimensional honeycomb structure:
      (H4APPIP)[Ln3(C2O4)(5.5)(H2PO4)2].5H2O (Ln = Er-Lu, APPIP = 1,4-bis(3
      aminopropyl)piperazine).
AB  - Four isostructural organically templated lanthanide oxalatophosphates,
      (H(4)APPIP)[Ln(3)(C(2)O(4))(5.5)(H(2)PO(4))(2)].5H(2)O (Ln = Er-Lu and APPIP =
      1,4-bis(3-aminopropyl)piperazine), have been synthesized under hydrothermal
      conditions and characterized by single-crystal and powder X-ray diffraction.
      Their structures contain LnO(8) trigonal dodecahedra linked by three bis
      bidentate oxalates to form layers in the (102) plane, which are connected by
      dihydrogen phosphate and bis-monodentate oxalate ligands to form a 3D framework.
      The charge-compensating tetraprotonated 1,4-bis(3-aminopropyl)piperazinium
      cations and lattice water molecules are located in the 12-membered ring straight
      channels. They are the first examples of organically templated lanthanide
      oxalatophosphates. The thermal stability, guest desorption-sorption properties,
      variable-temperature in situ powder X-ray diffraction, magnetic susceptibility,
      and photoluminescence spectrum of the Er compound and catalytic activity of the
      Yb compound for the Biginelli reaction have also been studied.

PMID- 19159317
TI  - Photofragmentation pathways and photodeposition of nanoparticles from a gas phase
      copper-containing precursor.
AB  - Pulsed laser excitation of bis(2,2,6,6-tetramethyl-3,5-heptanedionato)copper(II)
      (Cu(TMHD)(2)) in the gas phase produced neutral gaseous copper atoms and
      nanoparticulate copper deposits on substrates. Copper atoms were formed by the
      complete dissociation of the ligands from the metal. Time of flight mass
      spectrometry and resonance enhanced multiphoton ionization spectroscopy were used
      to study the details of this reaction and led to the discovery of other gaseous
      fragments that were produced by incomplete fragmentation of the ligands including
      monoligated species and coordinated ligand fragments. Laser-assisted chemical
      vapor deposition resulted in monodispersed nanoparticles under 100 nm in
      diameter. X-ray photoelectron spectroscopy and energy dispersive analysis of X
      rays were used to determine the elemental composition of the deposit. The
      relationships between the photofragmentation pathways and the deposited particles
      are discussed.

PMID- 19159318
TI  - Size effects in mechanical deformation and fracture of cantilevered silicon
      nanowires.
AB  - Elastic modulus and fracture strength of vertically aligned Si [111] nanowires (o
      = 100-700 nm) in an as-grown state have been measured using a new, multipoint
      bending protocol in an atomic force microscope. All wires showed linear elastic
      behavior, spring constants which scale with (length)(3), and brittle failure at
      the wire-substrate junction. The "effective" Young's modulus increased slightly
      (100 --> 160-180 GPa) as wire diameter decreased, but fracture strength increased
      by 2-3 orders of magnitude (MPa --> GPa). These results indicate that vapor
      liquid-solid grown wires are relatively free of extended volume defects and that
      fracture strength is likely controlled by twinning and interfacial effects at the
      wire foot. Small wires (100 nm) grown with a colloidal catalyst were the best
      performers with high modulus ( approximately 180 GPa) and fracture stress >1 GPa.

PMID- 19159319
TI  - Quantum description of the plasmon resonances of a nanoparticle dimer.
AB  - Using time-dependent density functional theory, we present a fully quantum
      mechanical investigation of the plasmon resonances in a nanoparticle dimer as a
      function of interparticle separation. We show that for dimer separations below 1
      nm quantum mechanical effects, such as electron tunneling across the dimer
      junction and screening, significantly modify the optical response and drastically
      reduce the electromagnetic field enhancements relative to classical predictions.
      For larger separations, the dimer plasmons are well described by classical
      electromagnetic theory.

PMID- 19159320
TI  - Synthesis and electrochemical characterization of halide, isocyanide, and alkynyl
      synthons containing the encumbered triangular cluster unit Pt3(mu-P(t)Bu2)3.
AB  - Useful synthons containing the tribridged triangular unit {Pt(3)} = [Pt(3)(mu
      P(t)Bu(2))(3)](+) were prepared starting from the known tricarbonyl derivative
      [{Pt(3)}(CO)(3)]Z, [(1(+))Z, Z = CF(3)SO(3)(-)]. This was easily converted into
      the monohalides {Pt(3)}(CO)(2)X [2, X = Cl; 3, X = Br; 4, X = I], by reaction
      with the appropriate halide salt. The coupling reaction between 2 and terminal
      alkynes in the presence of CuI afforded in good yields the sigma-alkynyl
      derivatives {Pt(3)}(CO)(2)(CC-R) [6, R = SiMe(3); 7, R = CC-SiMe(3); 8, R =
      C(6)H(5); 9, R = C(6)H(4)-4-Br; 10, R = C(6)H(4)-4-CCH; 11, R = 2-C(4)H(2)S-5
      CCH; 12, R = 9-C(14)H(8)-10-CCH], while desilylation of 6 or 7 with TBAF/THF
      gave, respectively, the derivatives 13 (R = H) and 14 (R = CCH). The stepwise
      elongation of the arylalkynyl chain was obtained by the Sonogashira coupling of
      10 with an excess of 1,4-diiodobenzene, which produced 15 (R = C(6)H(4)-4-CC
      C(6)H(4)-4-I), and by coupling the latter with an excess of 1,4-diethynylbenzene,
      which formed 16 (R = [C(6)H(4)-4-CC](3)H). Branched synthons were obtained by
      substitution of the carbonyl ligands with functional isocyanides; the reaction of
      an excess of CN-C(6)H(4)-4-R (R = I, CCH) with {Pt(3)}(CO)(2)H, 5, or with
      complex (1(+))Z afforded, respectively, {Pt(3)}(CN-C(6)H(4)-4-I)(2)H, 17, or
      [{Pt(3)}(CN-C(6)H(4)-4-R)(3)]Z [(18(+))Z, R = I; (19(+))Z, R = CCH]. The crystal
      structures of complexes 2, 8, and 9 were established by X-ray diffraction
      studies. The electrochemical characterization of representative examples of the
      clusters prepared in this work shows that all clusters are characterized by the
      presence of two oxidations; an analysis of ligands' effects on the redox
      processes is also included.

PMID- 19159321
TI  - Large cation-anion materials based on trinuclear ruthenium(III) salts of Keggin
      and Wells-Dawson anions having water-filled channels.
AB  - Reaction of the trinuclear ruthenium(III) cation
      [Ru(3)O(OOCCH(3))(6)(CH(3)OH)(3)](+) with the Keggin-type [alpha-GeW(11)O(39)](8
      ), [alpha-SiW(11)O(39)](8-), and [alpha-SiMo(12)O(40)](4-) and the Wells-Dawson
      type [alpha-P(2)W(18)O(62)](6-) polyanions in an aqueous, acidic medium resulted
      in plenary polyoxometalate-based materials
      K(2)Na[Ru(3)O(OOCCH(3))(6)(H(2)O)(3)][alpha-GeW(12)O(40)].10H(2)O (1),
      K(3)[Ru(3)O(OOCCH(3))(6)(H(2)O)(3)][alpha-SiW(12)O(40)].18H(2)O (2),
      K(3)[Ru(3)O(OOCCH(3))(6)(H(2)O)(3)][alpha-SiMo(12)O(40)].7H(2)O (3), and
      K(2)Na[Ru(3)O(OOCCH(3))(6)(H(2)O)(3)](3)[alpha-P(2)W(18)O(62)].26H(2)O (4),
      respectively. All four materials, 1-4, crystallize as sodium and/or potassium
      salts in the monoclinic space group P2(1)/n. Compounds 1-4 were characterized by
      IR, thermogravimetric analysis, and single-crystal/powder X-ray diffraction
      (XRD). The isolated solid-state frameworks, composed of cocrystallized trinuclear
      ruthenium cations and polyanions, exhibit nanosized voids filled with crystal
      waters. These water molecules can be removed reversibly upon heating under a
      vacuum, and powder XRD measurements demonstrated that the crystallinity of the
      compound was preserved. Sorption studies on ethanol and methanol were also
      performed.

PMID- 19159322
TI  - Nano-optical trapping of Rayleigh particles and Escherichia coli bacteria with
      resonant optical antennas.
AB  - Immobilizing individual living microorganisms at designated positions in space is
      important to study their metabolism and to initiate an in situ scrutiny of the
      complexity of life at the nanoscale. While optical tweezers enable the trapping
      of large cells at the focus of a laser beam, they face difficulties in
      maintaining them steady and can become invasive and produce substantial damage
      that prevents preserving the organisms intact for sufficient time to be studied.
      Here we demonstrate a novel optical trapping scheme that allows us to hold living
      Escherichia coli bacteria for several hours using moderate light intensities. We
      pattern metallic nanoantennas on a glass substrate to produce strong light
      intensity gradients responsible for the trapping mechanism. Several individual
      bacteria are trapped simultaneously with their orientation fixed by the asymmetry
      of the antennas. This unprecedented immobilization of bacteria opens an avenue
      toward observing nanoscopic processes associated with cell metabolism, as well as
      the response of individual live microorganisms to external stimuli, much in the
      same way as pluricellular organisms are studied in biology.

PMID- 19159323
TI  - Nanoscale oxidative patterning of metallic surfaces to modulate cell activity and
      fate.
AB  - In the field of regenerative medicine, nanoscale physical cuing is clearly
      becoming a compelling determinant of cell behavior. Developing effective methods
      for making nanostructured surfaces with well-defined physicochemical properties
      is thus mandatory for the rational design of functional biomaterials. Here, we
      demonstrate the versatility of simple chemical oxidative patterning to create
      unique nanotopographical surfaces that influence the behavior of various cell
      types, modulate the expression of key determinants of cell activity, and offer
      the potential of harnessing the power of stem cells. These findings promise to
      lead to a new generation of improved metal implants with intelligent surfaces
      that can control biological response at the site of healing.

PMID- 19159324
TI  - Copper/diethyl azodicarboxylate mediated regioselective alkynylation of
      unactivated aliphatic tertiary methylamine with terminal alkyne.
AB  - Mediated by copper/diethyl azodicarboxylate, regioselective alkynylation of
      unactivated aliphatic tertiary methylamine with terminal alkyne was successfully
      established. It is not necessary for the tertiary methylamines to be aryl
      substituted to modulate the properties of amines. The alkynylation reaction
      described here has the advantage of simple operation, mild reaction conditions,
      good to excellent yields, and no need to exclude air and moisture.

PMID- 19159325
TI  - Hybrid tin oxide nanowires as stable and high capacity anodes for Li-ion
      batteries.
AB  - In this report, we present a simple and generic concept involving metal
      nanoclusters supported on metal oxide nanowires as stable and high capacity anode
      materials for Li-ion batteries. Specifically, SnO(2) nanowires covered with Sn
      nanoclusters exhibited an exceptional capacity of >800 mAhg(-1) over hundred
      cycles with a low capacity fading of less than 1% per cycle. Post lithiation
      analyses after 100 cycles show little morphological degradation of the hybrid
      nanowires. The observed, enhanced stability with high capacity retention is
      explained with the following: (a) the spacing between Sn nanoclusters on SnO(2)
      nanowires allowed the volume expansion during Li alloying and dealloying; (b)
      high available surface area of Sn nanoclusters for Li alloying and dealloying;
      and (c) the presence of Sn nanoclusters on SnO(2) allowed reversible reaction
      between Sn and Li(2)O to produce both Sn and SnO phases.

PMID- 19159326
TI  - Sequential Cu(I)/Pd(0)-catalyzed multicomponent coupling and annulation protocol
      for the synthesis of indenoisoquinolines.
AB  - Copper-catalyzed coupling of imines, vinylstannanes, or alkynes and o-bromoaroyl
      chlorides followed by Pd(0)-catalyzed annulations afforded indenoisoquinolines.
      Protocols requiring minimal purifications were developed, providing new methods
      for the construction of combinatorial libraries.

PMID- 19159327
TI  - Aluminum nanoparticles as substrates for metal-enhanced fluorescence in the
      ultraviolet for the label-free detection of biomolecules.
AB  - We use finite-difference time-domain calculations to show that aluminum
      nanoparticles are efficient substrates for metal-enhanced fluorescence (MEF) in
      the ultraviolet (UV) for the label-free detection of biomolecules. The radiated
      power enhancement of the fluorophores in proximity to aluminum nanoparticles is
      strongly dependent on the nanoparticle size, fluorophore-nanoparticle spacing,
      and fluorophore orientation. Additionally, the enhancement is dramatically
      increased when the fluorophore is between two aluminum nanoparticles of a dimer.
      Finally, we present experimental evidence that functionalized forms of amino
      acids tryptophan and tyrosine exhibit MEF when spin-coated onto aluminum
      nanostructures.

PMID- 19159328
TI  - Periplasmic loop P2 of the MalF subunit of the maltose ATP binding cassette
      transporter is sufficient to bind the maltose binding protein MalE.
AB  - The Escherichia coli maltose transporter belongs to the ATP binding cassette
      (ABC) transporter superfamily. Recently, the crystal structure of the full
      transporter MalFGK2 in complex with the maltose binding protein (MBP) was
      determined [Oldham, M. L., et al. (2007) Crystal structure of a catalytic
      intermediate of the maltose transporter. Nature 450, 515-522]. Using liquid-state
      NMR, we find that the periplasmic loop P2 of MalF (MalF-P2) folds independently
      in solution and adopts a well-defined tertiary structure which is similar to the
      one found in the crystal. MalF-P2 interacts with the maltose binding protein,
      independent of the transmembrane region of MalF and MalG with an affinity of 10
      20 microM, in the presence and absence of substrate. Analysis of residual dipolar
      coupling (RDC) experiments shows that the conformation of the two individual
      domains of MalF-P2 is preserved in the absence of MalE and resembles the
      conformation in the X-ray structure. Upon titration of MalE to MalF-P2, the two
      domains of MalF-P2 change their relative orientation to accommodate the ligand.
      In particular, a conformational change of domain 2 of MalF-P2 is induced, which
      is distinct from the conformation found in the X-ray structure.

PMID- 19159329
TI  - Indirect modulation of nonmagnetic probes for force modulation atomic force
      microscopy.
AB  - Frequency-dependent changes for phase and amplitude images are demonstrated with
      test platforms of organosilane ring patterns, using force modulation atomic force
      microscopy (FM-AFM) with an alternate instrument configuration. The imaging setup
      using indirect magnetic modulation (IMM) is based on indirect oscillation of
      soft, nonmagnetic cantilevers, with spring constants <1 N m(-1). The tip is
      driven to vibrate by the motion of a tip holder assembly which contains
      ferromagnetic materials. The entire tip assembly is induced to vibrate with the
      flux of an external ac electromagnetic field, supplied by a wire coil solenoid
      placed underneath the sample plate. With the use of IMM, dynamic parameters of
      the driving frequencies and amplitude of the tip motion can be optimized to
      sensitively map the elastic response of samples. An advantage of this instrument
      setup is that a magnetic coating is not required to drive the periodic
      oscillation of the tip. The instrument configuration for IMM may not be practical
      for intermittent imaging modes, which often work best with stiff cantilevers.
      However, indirect actuation provides an effective approach for imaging with low
      force setpoints and is well-suited for dynamic AFM modes using continuous contact
      imaging.

PMID- 19159330
TI  - Evidence for the amphipathic nature and tilted topology of helices 4 and 5 in the
      closed state of the colicin E1 channel.
AB  - The membrane-bound closed channel structure of helices 4 and 5 (Lys-406-Asp-446)
      of the colicin E1 channel domain was investigated by using a site-directed
      fluorescence labeling technique. A bimane probe was covalently attached to a
      cysteine residue in a series of single-cysteine mutant proteins to scan each
      helix in a residue-by-residue fashion. A variety of fluorescence properties of
      the bimane fluorophore were measured for both the soluble and membrane-bound
      states of the channel peptide, including the fluorescence emission maximum,
      fluorescence anisotropy, and membrane bilayer penetration depth. The fluorescence
      properties were collated for construction of a membrane-bound topology model of
      helices 4 and 5 of the channel domain. Finally, the data reveal that both helices
      4 and 5 are two separate amphipathic alpha-helices that are situated parallel to
      the membrane surface. Dual fluorescence quencher analysis shows that helix 4
      adopts a tilted topology in which its C-terminus is more buried than its N
      terminus within the bilayer. In contrast, helix 5 is relatively solvent-exposed
      and located parallel to the interfacial region of the membrane surface. However,
      the loop region of both helices 4 and 5 was shown to be relatively buried within
      the bilayer. In addition, a least-squares fit of the data to a harmonic wave
      function indicated that both periodicity and frequency are typical for an
      amphipathic alpha-helix (3.75 +/- 0.1 residues per turn for helix 4 and 3.70 +/-
      0.1 residues per turn for helix 5). Squared residual plots of the harmonic wave
      function also reveal that the N-terminus of helix 4 is elongated by two residues
      from Lys-406 to Phe-404, while the C-terminus of helix 5 is elongated by three
      residues from Tyr-434 to Ile-437 upon membrane association.

PMID- 19159331
TI  - Rapid profiling of peptide stability in proteolytic environments.
AB  - The notorious degradation susceptibility of peptides is a major obstacle to their
      use as medicinal drugs. Assays with which the stability of peptides in complex
      proteolytic environments can be determined are thus indispensable for peptide
      drug development. Herein, we describe a new peptide proteolysis assay that meets
      that demand. It unites the high-throughput capacity of heterogeneous with the
      well-defined kinetic characteristics of homogeneous assay formats and operates on
      the cleavage-caused loss of a detection handle. We have confirmed the assay's
      accuracy with well-defined model interactions and proved its high versatility and
      robustness with a representative application where we determined the half-lives
      of 375 different peptides in a crude intestinal protease preparation. With this
      reliable, reproducible, and efficient assay the enzyme kinetics of any peptide
      protease interaction is accessible even for complex protease solutions.

PMID- 19159333
TI  - Computational prediction of antibody binding sites on tetracycline antibiotics:
      electrostatic potentials and average local ionization energies on molecular
      surfaces.
AB  - Enzyme linked immunosorbent assay (ELISA) was used for the analysis of
      tetracycline, chlortetracycline, oxytetracycline, and their transformed compounds
      in environmental water samples. The antibodies employed in ELISA showed high
      relative affinity for tetracycline, epitetracycline, chlortetracycline, and
      epichlortetracycline as compared to anhydrotetracycline, epianhydrotetracycline,
      and anhydrochlortetracycline. The specificity and crossreactivity of these
      antibodies are discussed in relation to the electrostatic potentials and average
      local ionization energies computed on the molecular surfaces of tetracycline
      antibiotics and their transformed compounds with an objective of identifying
      common features as well as differences that may be related to the experimentally
      observed variation in cross-reactivity values. The computations were performed at
      both the HF/STO-3G and HF/6-31+G* levels using the Gaussian 98 program. The
      results in this study are based upon molecular electrostatic potentials and local
      ionization energies computed on isodensity molecular surfaces. The surface
      electrostatic potentials are characterized in terms of a group of statistically
      defined quantities, which include the average deviation, the positive, negative,
      and total variances, positive and negative surface extrema, and a parameter
      indicating the degree of electrostatic balance.

PMID- 19159334
TI  - Comment on "Restricted geometry optimization: a different way to estimate
      stabilization energies for aromatic molecules of various types".

PMID- 19159332
TI  - Functional annotation and three-dimensional structure of Dr0930 from Deinococcus
      radiodurans, a close relative of phosphotriesterase in the amidohydrolase
      superfamily.
AB  - Dr0930, a member of the amidohydrolase superfamily in Deinococcus radiodurans,
      was cloned, expressed, and purified to homogeneity. The enzyme crystallized in
      the space group P3121, and the structure was determined to a resolution of 2.1 A.
      The protein folds as a (beta/alpha)7beta-barrel, and a binuclear metal center is
      found at the C-terminal end of the beta-barrel. The purified protein contains a
      mixture of zinc and iron and is intensely purple at high concentrations. The
      purple color was determined to be due to a charge transfer complex between iron
      in the beta-metal position and Tyr-97. Mutation of Tyr-97 to phenylalanine or
      complexation of the metal center with manganese abolished the absorbance in the
      visible region of the spectrum. Computational docking was used to predict
      potential substrates for this previously unannotated protein. The enzyme was
      found to catalyze the hydrolysis of delta- and gamma-lactones with an alkyl
      substitution at the carbon adjacent to the ring oxygen. The best substrate was
      delta-nonanoic lactone with a kcat/Km of 1.6 x 10(6) M-1 s-1. Dr0930 was also
      found to catalyze the very slow hydrolysis of paraoxon with values of kcat and
      kcat/Km of 0.07 min-1 and 0.8 M-1 s-1, respectively. The amino acid sequence
      identity to the phosphotriesterase (PTE) from Pseudomonas diminuta is 30%. The
      eight substrate specificity loops were transplanted from PTE to Dr0930, but no
      phosphotriesterase activity could be detected in the chimeric PTE-Dr0930 hybrid.
      Mutation of Phe-26 and Cys-72 in Dr0930 to residues found in the active site of
      PTE enhanced the kinetic constants for the hydrolysis of paraoxon. The F26G/C72I
      mutant catalyzed the hydrolysis of paraoxon with a kcat of 1.14 min-1, an
      increase of 16-fold over the wild-type enzyme. These results support previous
      proposals that phosphotriesterase activity evolved from an ancestral parent
      enzyme possessing lactonase activity.

PMID- 19159335
TI  - Fluorescence properties of hemicyanine in the nanoporous materials with varying
      pore sizes.
AB  - Hemicyanine dye molecules were put into the nanoporous materials (silicalite-1,
      zeolite-beta, and MCM-41) with different pore sizes. Fluorescence anisotropy
      measured from these systems indicated that the incorporated dye molecules were
      well-aligned along the straight channel of the zeolite pores, except for dye
      molecules in the largest pores of MCM-41. The fluorescence decay lifetimes were
      2.1, 1.7, and 1.1 ns, for the dyes in silicalite-1, zeolite-beta, and MCM-41,
      respectively. Significant increase in the fluorescence intensity and the
      fluorescence decay lifetime was observed with the decrease of the pore size. This
      was due to intramolecular rotational motion of the dye molecules more hindered in
      smaller pores, demonstrating the fluorescence properties of the dye molecule can
      be controlled at will by the choice of zeolite matrix.

PMID- 19159336
TI  - Charged droplet dynamics in the submicrometer size range.
AB  - The highly charged droplets produced by electrospray are of significant
      importance in analytical chemistry, particularly in mass spectrometry. In spite
      of this, little is known about the mechanisms of charge loss for highly charged
      droplets in the submicrometer size range. In this study, electropsrayed droplet
      charge loss dynamics in the submicrometer size range were examined for the first
      time using tandem differential mobility analysis (TDMA) of aerosol particles
      originally enclosed in methanol-water droplets. After complete droplet
      evaporation, the remaining aerosol particles carried the nonejected charges from
      droplets; thus, particle electrical mobility spectra are reflective of the
      electrical mobility spectra of droplets of similar size. Bayesian data inversion
      was used to compare measured electrical mobility spectra to models for droplet
      losing charge by Coulombic fission and by single ion emission. Data inversion
      showed that, at a size of approximately 40 nm, a transition of the mechanism of
      charge loss occurred. Methanol-water droplets larger than this size lost charge
      through Coulombic fissions at the Rayleigh limit with an effective surface
      tension of 0.050 N m(-1), while droplets in the 10-40 nm size range lost charge
      through ion emission, maintaining a constant electric field of 1.1 V nm(-1) on
      their surface during ion emission. This transition was observed experimentally
      for the first time in this study and is in good agreement with theoretical
      predictions from prior study of ion emitting nanodroplets. The data presented
      here provide the necessary link between studies of highly charged micrometer
      sized droplet and those of highly charged liquid clusters.

PMID- 19159337
TI  - New urea-based surfactants derived from alpha,omega-amino acids.
AB  - New anionic urea-based surfactants derived from alpha,omega-amino acids and in
      particular from beta-alanine were synthesized and their solution properties
      characterized by electrical conductivity, equilibrium surface tension, and steady
      state fluorescence spectroscopy techniques. Double-chain surfactants and the
      single-chain surfactant containing a sulfate head group exhibited the lowest
      critical micelle concentration (cmc) values and superior efficiency in lowering
      surface tension. All surfactants promoted adsorption relative to micellization,
      and micellar parameters were sensitive to the hydrophobicity of the amino acid
      residue. The polarity of the interfacial region, measured with the solvatochromic
      probe E(T)(30) (Reichardt's betaine dye), was similar to sodium dodecyl sulfate
      (SDS) micelles.

PMID- 19159338
TI  - Ultrasonic-irradiation-assisted oriented assembly of ordered monetite nanosheets
      stacking.
AB  - Bioactive monetite (anhydrous calcium hydrogen phosphate, CaHPO(4)) with orderly
      layered structure assembled by nanosheets has been successfully synthesized by a
      sonochemical-assisted method in the presence of cetyltrimethylammonium bromide
      (CTAB). The thicknesses of the nanosheets are 100-200 nm, and the lateral sizes
      are about 2 microm. Because of the strong affinity with the phosphate ions as
      well as the (200) faces of the crystals, CTAB molecules can make the formation
      and stabilization of monetite nanosheets with (200) exposed face. Ultrasonic
      irradiation makes the transition from disordered state to oriented state before
      the oriented assembly of monetite nanosheets. The ultrasonic irradiation provides
      enough external work to make the assemble process possible in thermodynamics. The
      drastic flow stirred by the supersonic jet in the solution accomplishes the
      transition and successive oriented assembly of nanosheets in dynamics. This study
      would offer a simple method to design and synthesize oriented-assembled
      materials.

PMID- 19159339
TI  - Absorption and fluorescence emission spectroscopic characters of size-expanded
      yDNA bases and effect of deoxyribose and base pairing.
AB  - We present an ab initio study of the optical absorption and emission spectra of
      size-expanded nucleic acid base analogues (yA, yT, yT-m, yG, yG-t2, and yC)
      obtained by benzo homologation (see Krueger, A. T.; Lu, H.; Lee, A. H. F.; Kool,
      E. T. Acc. Chem. Res. 2007, 40, 141 and references therein). Also examined were
      the effects of linking to deoxyribose and hydrogen bonding to their natural
      complementary bases (T, A, C, and G, respectively). The calculated excitation and
      emission energies are in good agreement with the measured data where experimental
      results are available. The geometries corresponding to the first excited singlet
      state of yA and yT are found to be quasi-planar, while those for yG and yC are
      nonplanar. In general, binding to deoxyribose will red shift the absorbance and
      fluorescence emission maxima of the y-bases. The ground-state geometries of the
      Watson-Crick analog base pairs (yAT, yTA, yGC, and yCG) are found to be planar,
      and the calculated interaction energies are very close to those of natural base
      pairs, indicating that the y-bases can pair with their natural complementary
      partners to generate stable base pairs. The base pairing has no significant
      effects on the fluorescence emission of yA, yC, and yT, but blue shifts the
      fluorescence emission of yG by 22 nm.

PMID- 19159340
TI  - pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4.
AB  - Nitrophorins are NO carrier proteins that transport and release NO through a pH
      dependent conformational change. They bind NO tightly in a low pH environment and
      release it in a higher pH environment. Experimental evidence shows that the
      increase in the NO dissociation equilibrium constant, K(d), is due mainly to an
      increase in the NO release rate. Structural and kinetic data strongly suggest
      that NPs control NO escape by modulating its migration from the active site to
      the solvent through a pH-dependent conformational change. NP2 and NP4 are two
      representative proteins of the family displaying a 39% overall sequence identity,
      and interestingly, NP2 releases NO slower than NP4. The proposal that NPs' NO
      release relies mainly on the NO escape rate makes NPs a very peculiar case among
      typical heme proteins. The connection between the pH-dependent conformational
      change and ligand release mechanism is not fully understood and the structural
      basis for the pH induced structural transition and the different NO release
      patterns in NPs are unresolved, yet interesting issues. In this work, we have
      used state of the art molecular dynamics simulations to study the NO escape
      process in NP2 and NP4 in both the low and high pH states. Our results show that
      both NPs modulate NO release by switching between a "closed" conformation in a
      low pH environment and an "open" conformation at higher pH. In both proteins, the
      change is caused by the differential protonation of a common residue Asp30 in NP4
      and Asp29 in NP2, and the NO escape route is conserved. Finally, our results show
      that, in NP2, the conformational change to the "open" conformation is smaller
      than that for NP4 which results in a higher barrier for NO release.

PMID- 19159341
TI  - Determination of kinetic parameters of enzyme-catalyzed reaction a + B + C -->
      products with the minimum number of velocity measurements.
AB  - Rapid-equilibrium rate equations are derived for the five different mechanisms
      for the enzymatic catalysis of A + B + C --> products using a computer. These
      rate equations are used to determine the minimum number of velocities required to
      estimate the values of the kinetic parameters. The rate equation for the
      completely ordered mechanism involves four kinetic parameters, and the rate
      equation for the completely random mechanism involves eight kinetic parameters.
      Therefore, the four to eight kinetic parameters can be estimated by determining
      four to eight velocities and solving four to eight simultaneous equations.
      General recommendations are made as to the choices of triplets of substrate
      concentrations {[A], [B], [C]} to be used to determine the velocities. The
      effects of 5% errors in the measured velocities, one at a time, are calculated
      and are summarized in tables. Calculations of effects of experimental errors are
      useful in choosing the triplets of substrate concentrations to be used to obtain
      the most accurate values of the kinetic parameters. When the kinetic parameters
      for A + B + C --> products are to be determined for the first time, it is
      recommended that the program for the completely random mechanism be used because
      it can identify the mechanism and determine the kinetic parameters in one
      operation.

PMID- 19159342
TI  - A role for the syntaxin N-terminus.
AB  - Intracellular membrane fusion steps in eukaryotes require the syntaxin family of
      SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein
      receptor) proteins. Syntaxins are regulated at several levels through
      interactions with regulatory proteins, including the SM (Sec1p/Munc18) proteins.
      Key to understanding this regulation is the characterization of different SM
      syntaxin binding interactions at the molecular level and in terms of their
      contribution to function in vivo. The most conserved SM-syntaxin binding mode is
      through interaction of the syntaxin's extreme N-terminal peptide with a
      hydrophobic pocket on the surface of the SM protein. Surprisingly, mutant
      versions of two different SM proteins abrogated for this binding display no
      discernable phenotypes in vivo. In this issue of the Biochemical Journal, Johnson
      et al. demonstrate that loss of the N-terminal binding interaction between the
      syntaxin UNC-64 and the SM protein UNC-18 severely impairs neuromuscular synaptic
      transmission in Caenorhabditis elegans, resulting in an unco-ordinated phenotype.
      In contrast, loss of a second mode of SM-syntaxin binding has no detectable
      effect. Collectively, these results suggest that, although different membrane
      trafficking steps are all regulated by SM-syntaxin interactions using similar
      binding modes, they are differentially regulated, highlighting the need for
      careful dissection of the binding modes.

PMID- 19159343
TI  - Insulin/IGF-like signalling, the central nervous system and aging.
AB  - Enormous strides in understanding aging have come from the discovery that
      mutations in single genes can extend healthy life-span in laboratory model
      organisms such as the yeast Saccharomyces, the fruit fly Drosophila melanogaster,
      the nematode worm Caenorhabditis elegans and the mouse. IIS [insulin/IGF (insulin
      like growth factor)-like signalling] stands out as an important, evolutionarily
      conserved pathway involved in the determination of lifespan. The pathway has
      diverse functions in multicellular organisms, and mutations in IIS can affect
      growth, development, metabolic homoeostasis, fecundity and stress resistance, as
      well as lifespan. The pleiotropic nature of the pathway and the often negative
      effects of its disruption mean that the extent, tissue and timing of IIS
      manipulations are determinants of a positive effect on lifespan. One tissue of
      particular importance for lifespan extension in diverse organisms is the CNS
      (central nervous system). Although lowered IIS in the CNS can extend lifespan,
      IIS is also widely recognized as being neuroprotective and important for growth
      and survival of neurons. In the present review, we discuss our current
      understanding of the role of the nervous system in extension of lifespan by
      altered IIS, and the role of IIS in determination of neuronal function during
      aging. The nervous system can play both endocrine and cell-autonomous roles in
      extension of lifespan by IIS, and the effects of IIS on lifespan and neuronal
      function can be uncoupled to some extent. Tissue-specific manipulation of IIS and
      the cellular defence mechanisms that it regulates will better define the ways in
      which IIS affects neuronal and whole-organism function during aging.

PMID- 19159344
TI  - Mechanisms of chemokine and antigen-dependent T-lymphocyte navigation.
AB  - T-lymphocyte trafficking is targeted to specific organs by selective molecular
      interactions depending on their differentiation and functional properties.
      Specific chemokine receptors have been associated with organ-specific trafficking
      of memory and effector T-cells, as well as the recirculation of naive T-cells to
      secondary lymphoid organs. In addition to the acquisition of tissue-selective
      integrins and chemokine receptors, an additional level of specificity for T-cell
      trafficking into the tissue is provided by specific recognition of antigen
      displayed by the endothelium involving the TCRs (T-cell antigen receptors) and co
      stimulatory receptors. Activation of PI3K (phosphoinositide 3-kinase) is a robust
      signalling event shared by most chemokine receptors as well as the TCR and co
      stimulatory receptors, contributing to several aspects of T-lymphocyte homing as
      well as actin reorganization and other components of the general migratory
      machinery. Accordingly, inhibition of PI3K has been considered seriously as a
      potential therapeutic strategy by which to combat various T-lymphocyte-dependent
      pathologies, including autoimmune and inflammatory diseases, as well as to
      prevent transplant rejection. However, there is substantial evidence for PI3K
      independent mechanisms that facilitate T-lymphocyte migration. In this regard,
      several other signalling-pathway components, including small GTPases, PLC
      (phospholipase C) and PKC (protein kinase C) isoforms, have also been implicated
      in T-lymphocyte migration in response to chemokine stimulation. The present
      review will therefore examine the PI3K-dependent and -independent signal
      transduction pathways involved in T-cell migration during distinct modes of T
      cell trafficking in response to either chemokines or the TCR and co-stimulatory
      molecules.

PMID- 19159345
TI  - Structure and function of the olfactory system: overview.

PMID- 19159346
TI  - Immunoelectron microscopic analysis of the distribution of tyrosine kinase
      receptor B in olfactory axons.
AB  - To determine the morphological basis for the neurotrophic effects of brain
      derived neurotrophic factor (BDNF) in the primary olfactory pathway (POP),
      tyrosine kinase receptor B (TrkB), a membrane-bound receptor for BDNF, was
      identified and localized in axons of olfactory receptor cells (ORC) of neonatal
      rat olfactory mucosa using immuno-histochemical and -cytochemical techniques.
      Initially, the immunospecificity of an anti-TrkB antibody that had been used as a
      specific antibody for full-length TrkB was confirmed in the olfactory mucosa.
      Then, a combination of a reduced osmium-LR-White and post-embedding immunogold
      technique was applied to ORC axons in the lamina propria just beneath the
      olfactory epithelium. Immunogold particles, which indicate TrkB immunoreactivity,
      were noted either in close association with the plasma membranes of ORC axons,
      and designated plasma-lemmal (PL), or within their cytoplasm, and designated
      cytoplasmic (CP). Most PL particles were seen in the CP portion of the axonal
      plasma membranes, suggesting that the anti-TrkB antibody binds to the membrane
      inserted TrkB that acts as a functional receptor. Some CP particles were on
      vesicular structures. Quantitative analysis demonstrated that the ratio of CP to
      PL particles was 7:3, and this ratio was constant between animals examined (n =
      5). Because membrane proteins are wrapped in vesicles and transported within the
      axonal cytoplasm and inserted into the plasma membrane to function there, the
      present study suggests that TrkB is transported within the cytoplasm of ORC axons
      and is positioned as a functional receptor for BDNF in their membranes.

PMID- 19159347
TI  - Architecture of odor information processing in the olfactory system.
AB  - Since the discovery of the superfamily of approximately 1000 odorant receptor
      genes in rodents, the structural simplicity as well as the complexity of the
      olfactory system have been revealed. The simple aspects include the one neuron
      one receptor rule and the exclusive convergence of projections from receptor
      neurons expressing the same receptors to one or two glomeruli in the olfactory
      bulb. Odor decoding in the olfactory cortex or higher cortical areas is likely to
      be a complicated process that depends on the sequence of signal activation and
      the relative signal intensities of receptors overlapping for similar but
      different odors. The aim of the present study was to investigate odor information
      processing both in receptors and in the olfactory cortex. At the receptor level,
      the similarity and difference in receptor codes between a pair of chiral odorants
      were examined using the tissue-printing method for sampling all the epithelial
      zones. In order to dissect odor-driven signal processing in the olfactory cortex
      by reducing cross-talk with the non-olfactory activities, such as cyclic
      respiration or other sensory inputs, an in vitro preparation of isolated whole
      brain with an attached nose was developed, and the methodologies and resulting
      hypothesis of receptor-sensitivity-dependent hierarchical odor information coding
      were reviewed.

PMID- 19159348
TI  - Synaptic organization of the olfactory bulb based on chemical coding of neurons.
AB  - Olfaction is one of the chemical senses in both vertebrate and invertebrate
      animals essential for a variety of social behaviors. Recent molecular biological
      and physiological studies using optical recording have indicated elaborate
      mechanisms in the main olfactory bulb for processing input from olfactory
      receptor neurons and control of output to higher centers in the brain. The
      current challenge is to identify a structural basis for understanding such
      elaborate molecular and functional organization. Immunocytochemistry and other
      advanced technologies have enabled us to label bulbar neurons selectively, and
      they have shown that the olfactory bulb has much greater heterogeneity in
      chemical and structural neuronal organization and in synaptic connectivity than
      previously believed. This review describes the structural aspects of the main
      olfactory bulb of rats and summarizes the findings for its synaptic organization
      based on chemical coding of neurons. Current uncertainties and issues that need
      to be clarified in the future are also discussed.

PMID- 19159349
TI  - Centrifugal innervation of the mammalian olfactory bulb.
AB  - Although it has been known for decades that the mammalian olfactory bulb receives
      a substantial number of centrifugal inputs from other regions of the brain,
      relatively few data have been available on the function of the centrifugal
      olfactory system. Knowing the role of the centrifugal projection and how it works
      is of critical importance to fully understanding olfaction. The centrifugal
      fibers can be classified into two groups, a group that release neuromodulators,
      such as noradrenaline, serotonin, or acetylcholine, and a group originating in
      the olfactory cortex. Accumulating evidence suggests that centrifugal
      neuromodulatory inputs are associated with acquisition of odor memory. Because
      the distribution of the terminals on these fibers is diffuse and widespread, the
      neuromodulatory inputs must affect diverse subsets of bulbar neurons at the same
      time. In contrast, knowledge of the role of centrifugal fibers from the olfactory
      cortical areas is limited. Judging from recent morphological evidence, these
      fibers may modify the activity of neurons located in sparse and discrete loci in
      the olfactory bulb. Given the modular organization of the olfactory bulb,
      centrifugal fibers from the olfactory cortex may help coordinate the activities
      of restricted subsets of neurons belonging to distinct functional modules in an
      odor-specific manner. Because the olfactory cortex receives inputs from limbic
      and neocortical areas in addition to inputs from the bulb, the centrifugal inputs
      from the cortex can modulate odor processing in the bulb in response to non
      olfactory as well as olfactory cues.

PMID- 19159350
TI  - Visualization of spatiotemporal differentiation of dopaminergic interneurons in
      adult mouse olfactory bulb using transgenic mice.
AB  - Olfactory bulb (OB) interneurons, predominantly periglomerular (PG) and granule
      (GR) cells, are derived from neural stem cells in the subventricular zone (SVZ)
      throughout life and migrate to the OB in the rostral migratory stream (RMS). In
      the adult superficial GR layer transgene expression was found, either enhanced
      green fluorescent protein or LacZ reporter driven by a 9 kb tyrosine hydroxylase
      (TH) promoter, that marked the dopamine (DA) phenotype. To demonstrate that the
      reporters and endogenous TH were similarly regulated expression of both
      parameters was shown to decline in the OB PG cells ipsilateral to odor
      deprivation produced by adult unilateral naris closure. The present findings
      suggested that DAergic differentiation might begin prior to progenitors reaching
      a PG position despite evidence that TH protein expression occurred only after PG
      cells received olfactory afferent stimulation. Of many genes previously
      hypothesized to regulate OB DA expression, regulated expression of the orphan
      receptor, Nurr1, but not the homeobox-containing genes, Dlx-1 and -2, was
      consistent with a role in regulation of the DA phenotype in adult mice OB. The
      studies show that transgenic lines are useful for analyzing spatiotemporal
      regulation by both intrinsic (programmed) and environmental factors in the
      neurogenesis of adult mouse OB DAergic interneurons.

PMID- 19159351
TI  - Radial artery running beneath the biceps tendon and its interrelation between the
      radial recurrent arteries.
AB  - A radial artery running beneath the biceps tendon was found in the cadaver of a
      Japanese woman during a student dissection course at Kumamoto University School
      of Medicine in 2006. The brachial artery bifurcated into the radial artery and
      the ulnar artery in the cubital fossa, and the radial artery twisted laterally
      running beneath the biceps tendon, and when it was situated laterally to the
      tendon, twisted distally at the level of the radial tuberosity, and then twisted
      medially again. After the radial artery passed over the biceps tendon, it turned
      distally and continued as a normal radial artery. The superficial brachial
      artery, which coexisted with the brachial artery, was given off from the axillary
      artery and it continued to the final twist of the radial artery. The course of
      this radial artery is similar to the arterial rings surrounding the biceps
      tendon, found during the same dissection course. The arterial rings were formed
      between the brachial artery and the radial artery, and their proximal origins ran
      beneath the biceps tendon, while the distal origins were superficial. The present
      arterial variation is thought to have occurred when the normal part of the radial
      artery in the cubital fossa was substituted by the arterial ring, coexisting with
      the superficial brachial artery, which usually disappears during normal
      development. Furthermore, it is suggested that a part of the arterial ring always
      remains as a radial recurrent artery.

PMID- 19159352
TI  - Ganglion cell density and oil droplet distribution in the retina of brown-eared
      bulbul (Hypsipetes amaurotis) [corrected].
AB  - This study was intended to determine the number and density of both retinal
      ganglion cells and the oil droplets of cone photoreceptor cells in brown-eared
      bulbul (Hypsipetes amaurotis). For this study birds were killed with proper dose
      of anesthetic (pentobarbital, 30 mg/kg), and the eyes were removed from the
      orbital cavity to isolate the retina. For the ganglion cell study retinal whole
      mount specimens were prepared and stained with 0.1% cresyl violet. The different
      types of oil droplets were counted from color microphotographs of freshly
      prepared retinal samples. The mean total number of ganglion cells was estimated
      at approximately 2.5 x 10(6); with an average density of 16 523 cells/mm(2). Two
      high-density areas, namely the central area (CA) and the dorso-temporal area
      (DTA), are located in the central and dorso-temporal retinas, respectively, in
      bulbuls (24 032 cells/mm(2) in the CA; 23 113 cells/mm(2) in the DTA). Small
      ganglion cells persisted in the highest density areas, whereas the largest soma
      sizes were found in the lowest density areas of the retina. Four types of
      different colored oil droplets - red, orange, green and clear - were identified
      with an average density of 29 062/mm(2). Among the different colors, the green
      oil droplets had a significantly higher population (13 083/mm(2)) than the others
      across the retina. The central retina had a significantly higher number of all
      types of oil droplets, at a density of 60 552/mm(2). The density and size of the
      different colored oil droplets were inversely related across the regions of the
      retina. Taken together, it is concluded that the CA of the retina is an excellent
      quality area for visual perception due to peak density of ganglion cells and oil
      droplets. Moreover, each specific oil droplet makes a distinct contribution to
      visual perception, thereby ensuring that the bird has a retina that best matches
      its natural environment and feeding behavior.

PMID- 19159353
TI  - Morphological analysis of the external anal sphincter motor nerve and its
      motoneurons in the cat.
AB  - To investigate the spinal neural circuitry that controls the tonus of the
      external anal sphincter (EAS) in the cat, the size distribution of EAS motor
      fibers and their motoneurons (MN) was examined, and the presence of muscle
      spindles in EAS musculature was also tested for. The size distribution of EAS
      motor fibers was examined after degeneration of afferent fibers and that of their
      MN was measured, after labeling the cells with horseradish peroxidase. Both
      distributions were unimodal, thereby demonstrating the difficulty of
      distinguishing between alpha and potential gamma MN; but muscle spindles were not
      found in the musculature. Mechanisms underlying the spinally controlled tonus of
      the EAS remain unclear, including the nature and role of spinal reflexes. It is
      argued that non-spindle sensory receptors in the anal canal may provide the
      sensory component of a reflex circuit that contributes to this tonus.

PMID- 19159354
TI  - Immunohistochemistry of connexin 43 throughout anterior pituitary gland in a
      transgenic rat with green fluorescent protein-expressing folliculo-stellate
      cells.
AB  - Folliculo-stellate (FS) cells in the anterior pituitary gland have been
      speculated to possess multifunctional properties. Because gap junctions (GJ) have
      been identified between FS cells, FS cells may be interconnected
      electrophysiologically by GJ and serve as signal transmission networks to
      modulate hormone release in the anterior pituitary gland. But whether GJ are
      localized among FS cells from the pars tuberalis through the pars distalis is
      unclear. The S100b-GFP transgenic rat has recently been generated, which
      expresses green fluorescent protein (GFP) specifically in FS cells in the
      anterior pituitary. This model is expected to be a powerful tool for studies of
      FS cells. The purpose of the present paper was therefore to examine the
      localization of GJ on connexin 43 immunohistochemistry throughout the anterior
      pituitary gland of S100b-GFP rats under confocal laser microscopy. The
      localization patterns of FS cells was also observed in primary culture of
      anterior pituitary cells and the question of whether GJ between FS cells are
      reconstructed in vitro was investigated. In vivo studies showed that GJ were
      present specifically between FS cells from the pars tuberalis to the pars
      distalis in the anterior pituitary gland. The appearance of FS cells was
      distinguished into two types, with localization of GJ differing between types. In
      vitro, it was observed for the first time that FS cells in primary culture could
      be categorized into two types. In vivo localization of GJ between FS cells was
      reconstructed in vitro. These morphological observations are consistent with the
      hypothesis that FS cells form an electrophysiological network throughout the
      anterior pituitary for signal transmission.

PMID- 19159355
TI  - Bioreductive activation of quinone antitumor drugs by mitochondrial voltage
      dependent anion channel 1.
AB  - The authors recently demonstrated that the mitochondrial voltage-dependent anion
      channel 1 (VDAC1) is involved in the sensitivity of cancer cells to
      furanonaphthoquinone (FNQ). The aim of the present study was to investigate
      whether mitochondrial VDAC1 reduces quinone antitumor drugs. The VDAC1 purified
      by immunoprecipitation reduced FNQ in the presence of nicotinamide adenine
      dinucleotide (NADH) and produced H(2)O(2). Blue native polyacrylamide gel
      electrophoresis demonstrated that the band that reduced FNQ NADH-dependently
      mainly included VDAC1. Because H(2)O(2) generation in catalyzing FNQ with NADH
      caused mitochondrial damage, the cytotoxic activity of FNQ was induced by VDAC1.
      In the quinone antitumor drugs, menadione (VK3), adriamycin and mitomycin C,
      mitochondrial VDAC1 bioreductively activated VK3. These results demonstrate that
      mitochondrial VDAC1 is a pharmacologic target for the treatment of tumor.

PMID- 19159356
TI  - Rare multiple combined anomaly of the vertebral vessels and bronchial artery.
AB  - Reported herein is a rare case of multiple vascular anomalies involving the
      vertebral vessels and the bronchial artery. In the present case the vertebral
      artery, which normally originates from the subclavian artery, arose directly from
      the cranial side of the aortic arch, just between the left common carotid and
      subclavian artery. Furthermore, the bilateral entry of the vertebral artery
      deviated to the upper level of the transverse foramen of the cervical vertebrae
      (C5). In addition, the left vertebral vein went through the transverse canal via
      the 5th and 7th transverse foramen, and drained into the left venous angle.
      Another conspicuous variation observed in this cadaver was the bronchial artery
      stemming from the left subclavian artery. This phenotype is an additional branch
      of bronchial arteries, which in normal cases arises from the descending aorta.
      These two anomalies could be explained by the deviation of the anlage for the
      left subclavian artery. The present report should be of interest for the
      clinician with regard to vascular anomalies in the neck and thoracic region, and
      may give insight into elucidating the developmental mechanism of angiogenesis.

PMID- 19159357
TI  - Levator glandulae thyroideae muscle with three slips.
AB  - Anatomical variations in the musculature surrounding the thyroid gland have the
      potential to cause iatrogenic injuries during neck and thyroid surgical
      procedures. Herein is presented a unilateral case found in an 83-year-old
      Caucasian female cadaver during a surgical mock thyroidectomy. The thyroid gland
      had a small pyramidal lobe with three muscular slips of levator glandulae
      thryroideae (LGT) muscle and a large tributary of the inferior thyroid vein
      descending posteriorly along the muscular slips. The nerve and arterial supply of
      the LGT was a twig of the ansa cervicalis and muscular branches from the superior
      thyroid artery, respectively. Clinicians who interpret imaging of the neck or
      surgeons who operate in the neck and especially on or near the thyroid gland
      should be aware of such a variation.

PMID- 19159358
TI  - Unusual pectoralis major muscle: the chondroepitrochlearis.
AB  - Presented herein is a case of an extremely rare muscle in the pectoral region. It
      involved an accessory muscular slip originating from the pectoralis major and
      inserting onto the medial epicondyle of the humerus and the medial intermuscular
      septum. According to the literature this muscle is defined as
      chondroepitrochlearis. The arterial and nervous supply to the muscle came from
      the lateral thoracic artery and the medial pectoral nerve, respectively. Clinical
      considerations of such a variation include ulnar nerve entrapment and
      functionally limited abduction of the humerus.

PMID- 19159359
TI  - Peroneotalocalcaneus muscle.
AB  - Variations within the musculature of the lateral compartment of the leg are
      uncommon. However, clinicians and radiologists should be aware of anatomical
      alterations in this region when involved in diagnosis or imaging interpretation.
      The present report describes a well-developed muscle of the lateral compartment
      of the leg that inserted distally onto the talus and calcaneus. This muscle could
      be considered a variation of the so-called peroneus quartus muscle. To the
      authors' knowledge this muscle variation has not been described as having an
      attachment onto the talus thus the term 'peroneotalocalcaneus muscle' is
      proposed.

PMID- 19159360
TI  - Accessory inferior thyroid artery and internal thoracic artery originating from
      the thyrocervical trunk.
AB  - During the routine dissection of an 86-year-old Caucasian male cadaver, an
      accessory inferior thyroid artery originating from the left suprascapular artery
      was detected. In addition to the existence of inferior and superior thyroid
      arteries, a third thyroid artery arising from the left suprascapular artery was
      present at the left of these arteries; this artery was determined as the
      accessory inferior thyroid artery. Again, the left internal thoracic artery arose
      from the thyrocervical trunk. The internal thoracic artery originated near the
      thyrocervical trunk's origin point and descended vertically. The thyrocervical
      trunk ended near the medial border of the anterior scalene muscle after giving
      rise to the inferior thyroid, transverse cervical and suprascapular arteries.

PMID- 19159361
TI  - Unusual case of occipital vertebra in a medieval skeleton.
AB  - The craniovertebral junction (CVJ) is a transitional region of the spine that
      exhibits extensive structural variability. Developmental defects include a vast
      array of anatomical anomalies that result from remnants of the proatlas and are
      grouped under the term 'occipital vertebra'. The purpose of the present paper is
      to describe the case of a medieval skeleton, which was found to display a
      previously unreported manifestation of occipital vertebra. It consisted of two
      large basilar processes that articulated with the anterior arch of the atlas. In
      addition, the left process exhibited a supplementary contact zone with the dens
      of the axis. These structural defects were associated with an accessory canal
      situated posterior to the right hypoglossal canal.

PMID- 19159362
TI  - Insertion of the pectoralis major into the shoulder joint capsule.
AB  - The pectoralis major muscle is subject to various morphologies. One presumably
      very rare variation is insertion of this muscle into the shoulder joint. During
      the routine dissection of the right upper extremity of an adult male cadaver a
      distinct separate tendinous insertion into the shoulder joint capsule was
      identified. This vertical tendon (7 mm x 6 cm) traveled just lateral to the long
      head of the biceps brachii muscle and terminated into the fibrous aspect of the
      joint capsule without penetrating it. Mechanical traction on the humeral
      attachment of the pectoralis major resulted in anteroinferior displacement of the
      shoulder joint capsule. The possible embryologic origin of this variation is
      discussed. Clinicians may wish to consider potential attachment of the pectoralis
      major into the capsule of the shoulder joint in diagnosing pathology of this
      region.

PMID- 19159363
TI  - Architecture and fiber type of the pyramidalis muscle.
AB  - The paired pyramidalis muscles are small triangular-shaped muscles that lie
      between the anterior surface of the rectus abdominus and the posterior surface of
      the rectus sheath. The precise function of pyramidalis muscles is unclear, but
      together the muscles are thought to tense the linea alba. The muscles are not
      always present, or are often unilateral, and vary greatly in size. Their wider
      inferior margins attach to the pubic symphyses and pubic crests, whereas their
      narrow superior margins attach to the linea alba. The gross anatomy and
      innervation of the pyramidalis muscles has been described by others, but their
      architecture and fiber type have not been determined in previous publications.
      The purpose of the present paper was therefore to investigate these parameters
      and place the findings into context for the literature available on this muscle.
      An example of bilateral pyramidalis muscles was recently encountered in a male
      cadaver that provided ample tissue for an analysis of its architecture and fiber
      type. The muscle mass, muscle length, fiber length, and pennation angle of muscle
      fibers were measured to ascertain physiological cross-sectional area and thereby
      estimate force production. Fiber type composition was also examined using
      immunofluorescent labeling. The results show that this is a muscle of mixed fiber
      type composition, similar to the rectus abdominus, and that the estimated forces
      generated by this muscle are relatively small.

PMID- 19159364
TI  - Unusual accessory tendon connecting the hallucal extensors.
AB  - During routine dissection of an adult human cadaver, a suite of tendinous
      anomalies was discovered in the left hallucal region. Whereas the main tendon of
      the extensor hallucis longus muscle inserted normally, two accessory tendons were
      found coursing medial and lateral to the main tendon. The most lateral tendon
      originated from a supernumerary muscle belly and merged with the tendon of
      extensor hallucis brevis to form a composite tendon. The most medial tendon
      crossed the metatarsophalangeal joint and joined the composite tendon deep to the
      tendon of extensor hallucis longus. A terminal tendon, consisting of these three
      contributions, inserted upon the proximal hallucal phalanx. This variant likely
      arose due to atypical differentiation of the common extensor muscle mass during
      development, and is of particular significance to clinicians performing
      arthroscopy, tendon transfers, and other surgical procedures.

PMID- 19159365
TI  - Large-caliber persistent sciatic artery with aneurysm.
AB  - Herein is reported a rare case of right persistent sciatic artery (PSA) in the
      cadaver of a 96-year-old woman who did not have any clinical manifestations
      related to this anomaly when alive. The anomalous PSA originated from the
      internal iliac artery, directed toward the infrapiriform foramen, and descended
      the dorsal side of the thigh. Approximately 20 mm inferior to the infrapiriform
      foramen, the PSA formed a relatively large aneurysm elongating for approximately
      30 mm in length. It then passed under the long head of the femoral biceps
      muscles, and reached the popliteal fossa, maintaining a constant caliber (approx.
      13 mm) as it went down distally. In contrast, the femoral artery was very narrow,
      and tapered at the level of the knee joint. In addition, the popliteal vein gave
      rise to two branches, one ran along with the sciatic artery and the other pierced
      the adductor muscles, and appeared on the ventral side of the thigh. It then
      drained into the deep femoral vein, which reached the pelvis via the femoral
      vein. The present case is an interesting example for clinicians who work in
      pelvic surgery.

PMID- 19159366
TI  - Trifurcation of brachial artery with variant course of radial artery: rare
      observation.
AB  - Variations in the arterial pattern of the upper limb have been observed
      frequently, either in the routine dissections or in clinical practice. The aim of
      the present study was to describe the anatomical, surgical and embryological
      importance of major arteries of upper limbs of human beings. The present article
      is the report of low division and trifurcation of brachial artery and abnormal
      course of radial artery (passing deep to the pronator teres muscle) found in a 45
      year-old embalmed male cadaver. Knowledge of the arterial variations in the upper
      limb is of considerable importance during invasive and non-invasive investigative
      procedures or orthopedic, reconstructive, or surgical procedures.

PMID- 19159367
TI  - Anomalous pectoral musculature.
AB  - Anomalous disposition of pectoral muscles was encountered in an adult female
      cadaver on the left side. A prominent cleft separating the sternocostal and
      clavicular portions of the pectoralis major was noticed. The fibers of pectoralis
      major were partially fused with the deltoid, resulting in obliteration of the
      deltopectoral groove. Interestingly, cephalic vein was seen traversing
      superficial to the clavicular portion of the pectoralis major and pierced it to
      drain into the axillary vein. The pectoralis minor was inserted mainly on the
      coracoid process and few fibers were found blending with the coracobrachialis and
      short head of biceps brachii. Further, pectoralis minimus, a rare anatomic
      variant, was also observed lying superior to pectoralis minor. It was innervated
      by a twig from the lateral pectoral nerve at its superficial surface. Awareness
      of possibility of such anomalous muscles is important for surgeons operating on
      the chest wall.

PMID- 19159368
TI  - Right vertebral artery as the fourth branch of the aortic arch.
AB  - The present report describes an anomalous case of the right vertebral artery
      arising as the last branch of the aortic arch identified in a 76-year-old
      Japanese male cadaver during dissection in the anatomical laboratory of Kanazawa
      Medical University. The aortic arch itself coursed normally but the right
      vertebral artery was uniquely situated at the fourth branch next to the
      brachiocephalic artery, the left common carotid artery, and the left subclavian
      artery. The anomalous right vertebral artery branched into the esophageal branch,
      the prevertebral branch, and the second right posterior intercostal artery, and
      finally entered the first costotransverse foramen at the thoracic region as it
      passed upward through the first to the seventh transverse foramina of the
      cervical vertebra. The left vertebral artery was normal. The development of the
      right vertebral artery may be described as follows: (i) the distal portion of the
      right dorsal aorta, which usually disappears, persisted and became united, via
      post-costal longitudinal anastomosis; (ii) the right dorsal aorta between the
      seventh and eighth intersegmental arteries lost its connection to the main
      structure; and (iii) the fusion of the originally paired dorsal aorta extended
      around the 11th segment, which was two segments away from the normal portion of
      the structure.

PMID- 19159369
TI  - Delivering drugs by the transdermal route: review and comment.
AB  - BACKGROUND: There are many advantages to administering drugs by routes that
      bypass the gastrointestinal tract. One such route is the transdermal in which the
      drug agent is applied to the skin in a patch or device of some type so that
      sufficient quantity penetrates the skin to exert a systemic effect. There are
      several theoretical advantages to this approach not the least of which is that
      the drug avoids being metabolized by the liver after absorption and that
      gastrointestinal irritation is avoided. AIMS: To discuss the various ways in
      which drugs can be persuaded to cross the skin barrier and also to discuss the
      adverse effects of transdermal administration. Technical advances have permitted
      an increasing number of drugs to be offered in the transdermal format.

PMID- 19159370
TI  - Finite element modelling of forearm skin wrinkling.
AB  - BACKGROUND/PURPOSE: Human skin is a complex multilayered material. Although there
      are many numerical models of skin in existence, which accurately simulate several
      of its complex mechanical characteristics, there are very few models that
      simulate wrinkling - a phenomenon common to all human skin. The purpose of this
      study was to develop a multilayer model of skin, which could simulate wrinkling
      more realistically than the existing models in the literature. METHOD: The skin
      on the volar forearm was wrinkled by displacing two tabs, which were attached to
      the skin surface towards each other. Eight volunteers were used in the
      experiment. The profiles of the wrinkles were measured using a customized laser
      profilometer system. The maximum range and average roughness of the wrinkle
      profiles were calculated. The multilayer model of skin consisted of the stratum
      corneum, dermis and underlying hypodermis. The constitutive equations for each
      layer were implemented into a finite element model and the wrinkling experiments
      were simulated. The results of the model were compared with the results of the
      experiments. RESULTS: The size of the wrinkles predicted by the model fell within
      the range of the wrinkle sizes measured in the experiments. The maximum range and
      average roughness differed by 34% and 43% from the corresponding mean
      experimental results, respectively. The results show that the proposed three
      layer skin model simulates wrinkling more realistically than either a single or a
      two-layer model. CONCLUSION: A three-layer model of skin has been developed and
      validated under the harsh conditions of wrinkling. It has been shown that a three
      layer model better simulates the wrinkling of skin as compared with models of
      fewer layers. The model has several applications, including simulating skin aging
      and the design of more realistic artificial skin. The model can also be used to
      study the interaction of surgical scalpels or razors with human skin with a view
      to improving their design.

PMID- 19159371
TI  - Evaluation of four non-invasive methods for examination and characterization of
      pressure ulcers.
AB  - BACKGROUND: Pressure ulcers are globally of major concern and there is need for
      research in the pathogenesis for early intervention. Early studies have suggested
      existence of a hypo-echogenic subepidermal layer at the location of pressure
      ulcers, visualized by ultrasound scans. As a continuation, we here report on
      usability of four non-invasive techniques for evaluation of pressure ulcers.
      METHODS: Fifteen pressure ulcers in stage 0-IV were examined using four different
      non-invasive techniques [redness index, skin temperature, skin elasticity (i.e.
      retraction time), and ultrasound scanning]. Measurements were made at the ulcer,
      5 cm from the ulcer, and at a reference skin location without ulcers. RESULTS:
      The redness index was, in all cases, higher at the ulcers than at the reference
      skin. Temperature measurements were rather scattered. Ultrasound scans showed a
      hypo-echogenic subepidermal layer at all pressure ulcers, but none at the
      reference points. The skin retraction time was often higher at the location of a
      pressure ulcer than at the reference location. We found no correlation between
      the stage of the ulcers and temperature, redness index, subepidermal layer
      thickness, or retraction time. CONCLUSION: We conclude that temperature and
      elasticity measurements do not alone characterize ulceration severity, although
      redness index in some cases provides a useful indication. We assume that a
      subepidermal layer found on ultrasound images may be a measure of the pressure
      that the skin has been subjected to, rather than of the severity of the pressure
      ulceration. This method may be useful for predicting whether the skin is at risk
      of developing pressure ulcers. More studies are needed.

PMID- 19159372
TI  - The irritant potential of n-propanol (nonanoic acid vehicle) in cumulative skin
      irritation: a validation study of two different human in vivo test models.
AB  - BACKGROUND/PURPOSE: Human in vivo cumulative irritation tests with low-grade
      irritants simulate real-life exposure to skin irritants. The test outcome depends
      not only on the substance tested but also on the design of the assay. More than
      one experimental irritant is usually used because chemicals have diverse
      mechanisms of action on the skin. We used sodium lauryl sulfate (SLS) and
      nonanoic acid (NON) in three different concentrations plus their vehicles, water
      and n-propanol, respectively, to validate our test models and to optimize test
      concentrations. METHODS: Healthy volunteer forearm skin was exposed in two
      different cumulative test models: a repeated open model (ROAT) and an exaggerated
      wash test model. ROAT: 10-min daily exposures for 5+4 days (no irritation on
      weekend) to SLS 0% (water), 0.5%, 1.0% and 2.0% on the right arm and NON 0% (n
      propanol neat), 10%, 20% and 30% on the left arm. Wash test: induction of
      irritation by three daily washings for 6 days and maintenance of the dermatitis
      by two daily washings for 12 days with SLS 0%, 5%, 10% and 15% or NON 0%, 30%,
      40% and 50%. Reactions were evaluated clinically and instrumentally
      (transepidermal water loss, colorimetry and hydration) at sequential time points.
      Additionally, for the wash test, subjective pain scores were obtained from the
      volunteers. RESULTS: In the ROAT, n-propanol exhibited irritation potential at
      the level of SLS 1.0% and, by visual scoring, was only found to be significantly
      different from the two highest concentrations of NON (20% and 30%). In the wash
      test, n-propanol was much less irritating than SLS, and it could only be
      distinguished statistically from NON (any concentration) by visual reading. For
      both test models, n-propanol, by instrumental measurements, was not significantly
      different from any NON concentration. CONCLUSION: In cumulative irritation test
      assays, n-propanol appears to be quite irritant itself and may thus be a
      significant contributor to NON irritation. Moreover, n-propanol was more irritant
      in the ROAT compared with the wash test.

PMID- 19159373
TI  - Development of a new evaluation method for cheek sagging using a Moire 3D
      analysis system.
AB  - BACKGROUND/AIMS: Facial sagging becomes progressively noticeable with aging.
      Previously developed methods to study facial sagging measure the shape of sagging
      skin, evaluate skin properties such as elasticity or flexibility or visually
      score the degree of sagging using a photo scale. However, the practical use of
      these methods has shortcomings and is thus limited to advanced levels of sagging.
      In this study, we attempted to overcome the shortcomings of those previous
      methods. METHODS: Fourteen points were marked on the cheek of each subject and
      photographed using a Moire three-dimensional (3D) camera with the subject facing
      first frontward and then downward. The absolute 3D coordinates (x, y, z) of the
      14 points from the control point (0, 0, 0) were calculated. Subsequently, the
      skin surface displacements at the 14 points between the frontward and downward
      images were analyzed along the x, y, and z axes. The values were compared by age
      and by sag scores obtained from the photo scales. RESULT: The displacement values
      strongly correlated with age and with the sag score. In addition, this new method
      revealed characteristic differences of sagging between women in their 60s and
      those in their 70s. CONCLUSION: This method, using Moire 3D analysis, revealed
      slight, continuous and characteristic changes of cheek skin sagging without
      causing any discomfort to the subjects. These results are consistent with
      people's visual impression. The results indicate the usefulness of this method in
      skin research.

PMID- 19159374
TI  - Point-spread imaging for measurement of skin translucency and scattering.
AB  - BACKGROUND/PURPOSE: The translucency of skin has long been identified as an
      important cue for healthy and youthful looking skin. There is currently no
      universal definition for skin translucency let alone a measurement method. We
      propose that skin translucency is the light scattering beneath skin surface. We
      demonstrate the use of polarization gated point spreading imaging for non
      invasive, in vivo measurement of the translucency and the reduced scattering
      coefficient m's of skin. METHODS: We developed a polarization-gated point-spread
      imaging system to measure the spread of the incident pencil-thin laser beam on
      the skin. Skin translucency was calculated as the spread of the laser beam. From
      the measurement of the shift of the light diffuse center from the light injection
      point, the reduced scattering coefficient m's of the skin was calculated. We
      validated the measurement technique with milk as an in vitro model for skin.
      RESULTS AND CONCLUSION: The measured m's of milk solution was found to be
      linearly proportional to the milk concentration, in agreement with Beer's law.
      The calculated translucency decreased as the milk concentration increased or as
      the reduced scattering coefficient m's increased. It was also found that the
      translucency decreased as the absorption coefficient of the milk solution
      increased. The measured translucency of a set of custom made clay tiles
      correlated well with the consumer perception of the incremental ranking of the
      translucency. In vivo measurement of skin translucency and the reduced scattering
      coefficient m's were carried out on several volunteers. The measured reduced
      scattering coefficient m's was in agreement with those in the literature. The
      measured skin translucency for different skin ethnicities of Caucasian, North
      Asian, South Asian and African American were in line with the expectation that
      skin translucency decreases as the skin color gets darker.

PMID- 19159375
TI  - Measurement of skin stretch using digital image speckle correlation.
AB  - BACKGROUND/PURPOSE: The surface of the skin is covered by intersecting grooves
      and ridges which produce characteristic skin surface patterns. It has been
      suggested that these folds provide a reserve of tissue, allowing the skin to
      stretch during normal muscle movements. More so, skin is anisotropic and under
      constant tension. Therefore, to characterize skin displacement following stretch,
      a discrete, description of the in-plane skin displacement during stretch is of
      interest. We introduce the use of digital image speckle correlation (DISC), a non
      contact technique, to map, in two dimensions, the surface deformation patterns
      resulting from skin stretching. METHODS: We analyze skin stretch under the
      mechanical action of a film former applied on a defined square surface on the
      back of the hand. This is achieved by taking a series of images, during the
      drying process of the film former. The images are then analyzed with DISC to
      create vector diagram and projection maps, from which we can obtain spatially
      resolved information regarding the skin displacement. RESULTS: We first show that
      DISC can provide spatially resolved information at any time point during the
      drying process: areas of de-wetting, wetting were identified using projection
      maps; we then extracted the value of the drying time. Finally using a vector map,
      we show the orientation of the skin displacement during stretching and calculated
      the magnitude of the total stretch. CONCLUSIONS: We have shown previously that
      DISC can be used to determine skin mechanical properties and muscular activity.
      We show here that DISC, as a non-contact technique, can map, in two dimensions,
      the surface deformation patterns of a polymer solution on a substrate at any time
      point during the drying process. DISC analysis generates for each speckle of the
      sample analyzed, the orientation and magnitude of displacement of the polymer
      solution. DISC can map in two dimensions the deformation undergone by the
      substrate and skin stretch is measured in this particular case. We therefore show
      that the DISC method, as a non-contact technique has great potential for
      characterization of film formation and is a potential clinical research tool for
      the measurement of epidermis stretch and epidermis properties.

PMID- 19159376
TI  - Transcutaneous pO2 imaging during tourniquet-induced forearm ischemia using
      planar optical oxygen sensors.
AB  - BACKGROUND: Oxygen-dependent quenching of luminescence using transparent planar
      sensor foils was shown to overcome the limitations of the polarographic electrode
      technique in an animal model. This method was then transferred to a clinical
      setting to measure the transcutaneous pO(2) (p(tc)O(2)). METHODS: In six healthy
      subjects, a cuff on the upper arm was occluded up to 20 mmHg above systolic
      pressure and released after 8 min. P(tc)O(2) was measured at the lower arm every
      30 s before, during, and up to 20 min after cuff occlusion (40 degrees C applied
      skin temperature) using luminescence lifetime imaging (LLI) of platinum(II)
      octaethyl-porphyrin immobilized in a polystyrene matrix. For validation, the
      polarographic Clark electrode technique was applied in close proximity, and
      measurements were conducted simultaneously. RESULTS: P(tc)O(2) measurements
      before (70.8+/-19.1 vs. 66.2+/-7.7 mmHg) and at the end of ischemic (2.7+/-1.2
      vs. 3.6+/-1.7 mmHg) and reperfusion phases (72.2+/-3.6 vs. 68.4+/-8.9 mmHg) did
      not differ significantly using the Clark electrode vs. LLI. At both the initial
      ischemic and the reperfusion phases, the Clark electrode measured a faster
      decrease or increase, respectively, in p(tc)O(2) because of the oxygen
      consumption occurring in this method. CONCLUSION: The presented method provides
      accurate and reproducible p(tc)O(2) values under changing microcirculatory
      conditions. The lack of oxygen consumption during measurement allows both a more
      realistic estimation of p(tc)O(2) than compared with the gold standard and
      permanent use in regions with critical oxygen supply.

PMID- 19159377
TI  - Alteration of skin mechanics by thin polymer films.
AB  - BACKGROUND/PURPOSE: High molecular weight polymers such as proteins and
      polysaccharides have been commonly employed in cosmetic practice to induce skin
      tightness. The effect is perceived by users as an increase in skin tightness
      (firmness) accompanied by skin smoothing and elimination of wrinkles and lines.
      The aim of the study was to assess whether high molecular weight synthetic
      polymers, in the form of simple skin treatment formulations, could modify
      mechanical properties of natural skin as well as artificial skin models. METHODS:
      In experiments involving natural skin, the formulations were employed to treat
      the inner forearm of five panelists, who ranged in age from mid-20s to mid-40s.
      Indentometric analysis also included rubber skin models, with various
      viscoelastic characteristics, modified by deposition of thin polymer films on the
      surface. Polymers such as polyvinylpyrrolidone, polyquaternium-55, polyimide-1,
      VP/acrylates/lauryl methacrylate copolymer, and sodium alginate were
      investigated. The effects of the products were quantified by mechanical skin
      indentation performed at small deformations. Data analysis was performed using
      the Hertz theory of contact mechanics, which included the calculation of
      fundamental parameters such as the modulus of elasticity. RESULTS: The
      indentometric analysis revealed an increase in the Young's modulae for both
      artificial and natural skin as a result of treatment with the polymers. The
      effect was dependent on the amount of deposited product, which was varied in the
      range from 0.053 to 1.06 mg/cm(2) of polymer. The observed increases in Young's
      modulae were typically from about 0.7 to 1.4 x 10(4) N/m(2) for untreated skin to
      1.4-2.0 x 10(4) N/m(2) for polymer-modified skin, depending on the polymer
      structure (molecular weight) and the amount of deposition. By the analysis of
      artificial skin models, it was found that the magnitude of stiffening depends on
      the mechanical characteristics of the base material. Softer skin models displayed
      larger increases in Young's modulus after polymer treatment than stiffer skin
      models. Also, the analysis of skin models suggested that polymeric treatments can
      lower the viscoelasticity of skin as demonstrated by decreased values of
      hysteresis loss factors calculated from indentation force vs. penetration depth
      plots. The performance of the polymers was also shown to be dependent on ambient
      humidity with the most hygroscopic materials loosing their stiffening effect at
      high humidity. CONCLUSIONS: The data indicate that high molecular weight polymers
      can be useful as skin stiffening, firming, or tightening agents. This was
      demonstrated by indentometric, mechanical analysis of natural skin and artificial
      skin models, and by determining Young's modulae and viscoelastic parameters.

PMID- 19159378
TI  - Use of high-frequency ultrasound in the assessment of injectable dermal fillers.
AB  - BACKGROUND: The use of dermal fillers for enhancing lips and reducing wrinkles is
      currently one of the fastest growing sectors of the cosmetic surgery market.
      There are numerous fillers available, some are synthetic others are isolated from
      biological material. Once injected the fillers have a varied lifespan ranging
      from months to years depending upon the material, site of injection and
      individual response. Current assessment techniques of filler performance are
      mostly limited to evaluations of the skin surface topography, and not to what is
      happening to the filler beneath the skin surface. The aim of this work was to see
      if high-frequency ultrasound could be used to image and measure filler dimensions
      in situ. METHOD: This was a pilot study of six healthy female volunteers aged 36
      53 visiting the surgical outpatients department of a hospital in Glasgow.
      Volunteers had been injected with filler material into their upper lip 6 months
      before the visit. The patients all had their upper lip scanned using high
      frequency ultrasound. The subsequent images were then assessed using the scanner
      software to assess the dimensions of the filler. RESULTS: The filler material was
      clearly visible with the ultrasound and subsequently measurable in each scan.
      Each scan procedure was completed within a short time period meaning quantitative
      data could be acquired with minimum trauma to the volunteer. The scan images and
      data also provided valuable information for the volunteers and reinforced their
      perception of the fillers effect on their features. CONCLUSIONS: High-frequency
      ultrasound scanning provides a non-invasive, convenient and rapid technique for
      the assessment of filler performance. This pilot study produced three valuable
      pieces of information: The ultrasound can image the filler material from which
      quantitative measurements can be made. The technique is rapid and cost effective
      ...This investigation helped to reinforce the volunteer's perception of the
      filler effect.

PMID- 19159379
TI  - Visualizing nuclei in skin cryosections: viable options to 4'6-diamidino-2
      phenylindol for confocal laser microscopy.
AB  - BACKGROUND: Visualization of nuclei in skin (cryo-) sections is essential for
      both, rapid overview and reliable orientation within skin samples. Therefore,
      nuclear staining is a very common counterstain for immunohistochemical studies of
      human skin as this nuclear staining precisely depicts the cellular distribution
      within the epidermis. Moreover, it clearly shows the epidermal-dermal border as
      well as the transition zone between the living and the cornified layers of the
      epidermis. For standard epifluorescence microscopy, 4'6-diamidino-2-phenylindol
      (DAPI) is commonly used. For confocal laser scanning microscopy (CLSM), however,
      DAPI is often not suitable because its excitation maximum is in the ultraviolet
      (UV) range (Ex(max) 359 nm) when bound to DNA, and UV lasers and the
      corresponding optics are not part of CLSM standard configuration. METHODS: In
      order to find an adequate DAPI substitute that is excitable with standard visible
      light lasers, the following nuclear stains were tested: LOLOt-1 iodide (Ex(max)
      565 nm), TOTO s -3 iodide (Ex(max) 642 nm), LO-PROt-1 iodide (Ex(max) 567 nm),
      SYTO s 84 (Ex(max) 567 nm), SYTO s 85 (Ex(max) 567 nm), SYTOX s Green (Ex(max)
      488 nm) and SYTOX s Orange (Ex(max) 547 nm), Propidium iodide (Ex(max) 535 nm).
      Besides optimal concentration and incubation time, following criteria were also
      evaluated: photobleaching, background, e.g. cytoplasmic staining of RNA, and
      sensitivity to different fixation conditions (unfixed, IEM fixation, PLP fixation
      and PFA fixation). RESULTS: According to these criteria Sytox s Green showed the
      best overall staining score and can be used for variously fixed skin samples and
      shows a distinct and stable green nuclear fluorescence.

PMID- 19159380
TI  - Cutaneous differences between Black, African or Caribbean Mixed-race and
      Caucasian women: biometrological approach of the hydrolipidic film.
AB  - BACKGROUND/PURPOSE: Studies about the adaptation of ethnic types of skin to an
      environment radically different from their original environment are rarely found
      in the literature. We have evaluated the differences in the skin surface
      properties of three ethnic groups: Black, African or Caribbean Mixed-race and
      Caucasian women living in defined climatic conditions. METHODS: Biometrological
      evaluations of barrier function were made by measurements of transepidermal water
      loss (TEWL), skin hydration and skin dryness. To approach the skin protective
      coating we evaluated cutaneous lipid index (LI), cutaneous pH, skin frictional
      properties and skin wettability. RESULTS: The TEWL, cutaneous hydration, dryness
      and LI show no significant difference. Volunteers were given a self-assessment
      questionnaire regarding their hygiene and cosmetic practices. The results show
      that 100% of Black and 92% of African or Caribbean Mixed-race women use a
      hydrating product daily vs. only 16% of Caucasian women. They justify this
      practice by the 'dry skin' sensation that they feel if they do not use a
      moisturizer. We tried to assess objectively to the protective coating surface of
      the human skin: the hydrolipidic cutaneous film, by measurements of pH,
      frictional properties and wettability which show significant differences. We may
      suppose that the hydrophilic/lipophilic balance of the skin in these three ethnic
      groups is different. CONCLUSION: To interpret these results as accurately as
      possible, it would be interesting, in future investigations on the ethnic types
      of skin, to evaluate the sweat secretion, and to analyse each element of the
      sebaceous secretions quantitatively as well as qualitatively.

PMID- 19159381
TI  - Non-invasive evaluation techniques to quantify the efficacy of cosmetic anti
      cellulite products.
AB  - BACKGROUND: The majority of women suffer from the unattractive sight of dimpling
      skin on the thighs and buttocks, globally known as cellulite. Cellulite can be
      regarded as the most investigated non-disease, because, from the cosmetic
      viewpoint, most women desire a reduction in cellulite severity. Despite
      investigations made, cellulite is still not well understood at the cellular
      level, which leads to controversy regarding the investigative methods for
      cellulite reduction as well as the development of products to treat cellulite
      skin. OBJECTIVE: The aim of our work was to improve the set up of
      macrophotography for making images of dimpled skin and to automatize image
      analysis of 20 MHz ultrasound imaging - these two methods being just two of a
      variety of available methods for investigating cellulite skin. METHODS:
      Macrophotography was standardized on the aspects of volunteer's positioning, skin
      illumination, background used, and camera position. It was performed before,
      during and after a 3-month-treatment of a cosmetic product. Scoring assessments
      of the generated images were made by the volunteers themselves as well as by six
      trained experts. Ultrasound imaging was performed at the baseline visit in order
      to correlate the newly developed analysis with the visually rated cellulite
      score. A second study is also presented showing a variety of parameters that can
      be used for cosmetic testing of cellulite products: skin firmness, blood
      circulation and circumferential thigh measurements. RESULTS: Standardization of
      macrophotography minimized differences in image features between assessment
      times, therefore, enabling follow-up rating assessments of the images. A custom
      made rating program simplified the scoring procedure by presenting images as
      blind and randomized, and by implementing computer-based analysis using an online
      rating scale. Volunteers and experts scored significant improvement of skin
      appearance over the course of a 3-month cosmetic treatment. Image analysis of
      ultrasound imaging was automatized, and a modification of the commonly known
      roughness parameter Ra was implemented to characterize cellulite severity.
      Comparison with the visually rated cellulite score showed an existing correlation
      between the score and the modified parameter Ra(m). Further parameters
      investigated in an exemplary study, as mentioned above, demonstrated a
      significant improvement of skin appearance after treatment with a cosmetic
      product. CONCLUSIONS: Macrophotography and ultrasound imaging can be regarded as
      important tools for determining and quantifying the aspects of cellulite. With a
      gold standard missing for investigating cellulite severity, these two methods may
      not determine cellulite at the cellular level, but they do characterize the skin
      appearance so typical for cellulite. Combined with a variety of other methods,
      macrophotography and ultrasound imaging can very well define cellulite-reducing
      efficacy from the cosmetic point of view.

PMID- 19159382
TI  - Border detection in dermoscopy images using statistical region merging.
AB  - BACKGROUND: As a result of advances in skin imaging technology and the
      development of suitable image processing techniques, during the last decade,
      there has been a significant increase of interest in the computer-aided diagnosis
      of melanoma. Automated border detection is one of the most important steps in
      this procedure, because the accuracy of the subsequent steps crucially depends on
      it. METHODS: In this article, we present a fast and unsupervised approach to
      border detection in dermoscopy images of pigmented skin lesions based on the
      statistical region merging algorithm. RESULTS: The method is tested on a set of
      90 dermoscopy images. The border detection error is quantified by a metric in
      which three sets of dermatologist-determined borders are used as the ground
      truth. The proposed method is compared with four state-of-the-art automated
      methods (orientation-sensitive fuzzy c-means, dermatologist-like tumor extraction
      algorithm, meanshift clustering, and the modified JSEG method). CONCLUSION: The
      results demonstrate that the method presented here achieves both fast and
      accurate border detection in dermoscopy images.

PMID- 19159383
TI  - Influence of age and regional differences on skin elasticity as measured by the
      Cutometer.
AB  - BACKGROUND/AIM: Aging of skin is accompanied by decrease of skin elasticity.
      Using the noninvasive suction device Cutometer, we evaluated the age and regional
      body differences of the viscoelastic properties of human skin. The objectives of
      this study were to evaluate the correlation between age and the biomechanical
      parameters and the regional skin variations. METHODS: A total of 96 healthy women
      aged 20-75 years were included in this study. The biomechanical properties of the
      skin were measured by using the Cutometer. Measurements were made on the face,
      upper arm and back. RESULTS: The age of subjects showed significant positive
      correlation with R4 and R6, and negative correlation with R2, R5 and R7. The face
      showed bigger changes of elastic properties than the arm and the back.
      Especially, the R7 of face was most significantly decreased with aging. We could
      estimate the so-called 'skin age' by using a correlation equation for this
      parameter. CONCLUSION: The viscoelastic properties were significantly influenced
      by aging. Also, significant regional variations in the viscoelastic properties
      were observed. Skin elasticity measurement is useful for the quantitative
      evaluation of age-related changes.

PMID- 19159384
TI  - Diagnostic image analysis of malignant melanoma in in vivo confocal laser
      scanning microscopy: a preliminary study.
AB  - BACKGROUND/PURPOSE: In this study we assessed the applicability of image analysis
      and a machine learning algorithm on diagnostic discrimination of benign and
      malignant melanocytic skin tumours in in vivo confocal laser-scanning microscopy
      (CLSM). METHODS: A total of 857 CLSM tumour images including 408 benign nevi and
      449 melanoma images was evaluated. Image analysis was based on features of the
      wavelet transform. For classification purposes we used a classification tree
      software (CART). Moreover, automated image analysis results were compared with
      the prediction success of an independent human observer. RESULTS: CART analysis
      of the whole set of CLSM tumour images correctly classified 97.55% and 96.32% of
      melanoma and nevi images. In contrast, sensitivity and specificity of 85.52% and
      80.15% could be reached by the human observer. When the image set was randomly
      divided into a learning (67% of the images) and a test set (33% of the images),
      overall 97.31% and 81.03% of the tumour images in the learning and test set could
      be classified correctly by the CART procedure. CONCLUSION: Provided automated
      decisions can be used as a second opinion. This can be valuable in assisting
      diagnostic decisions in this new and exciting imaging technique.

PMID- 19159385
TI  - Machine-learning classification of non-melanoma skin cancers from image features
      obtained by optical coherence tomography.
AB  - BACKGROUND/PURPOSE: A number of publications have suggested that optical
      coherence tomography (OCT) has the potential for non-invasive diagnosis of skin
      cancer. Currently, individual diagnostic features do not appear sufficiently
      discriminatory. The combined use of several features may however be useful.
      METHODS: OCT is based on infrared light, photonics and fibre optics. The system
      used has an axial resolution of 10 mum, lateral 20 mum. We investigated the
      combined use of several OCT features from basal cell carcinomas (BCC) and actinic
      keratosis (AK). We studied BCC (41) and AK (37) lesions in 34 consecutive
      patients. The diagnostic accuracy of the combined features was assessed using a
      machine-learning tool. RESULTS: OCT images of normal skin typically exhibit a
      layered structure, not present in the lesions imaged. BCCs showed dark globules
      corresponding to basaloid islands and AKs showed white dots and streaks
      corresponding to hyperkeratosis. Differences in OCT morphology were not
      sufficient to differentiate BCC from AK by the naked eye. Machine-learning
      analysis suggests that when a multiplicity of features is used, correct
      classification accuracies of 73% (AK) and 81% (BCC) are achieved. CONCLUSION: The
      data extracted from individual OCT scans included both quantitative and
      qualitative measures, and at the current level of resolution, these single
      factors appear insufficient for diagnosis. Our approach suggests that it may be
      possible to extract diagnostic data from the overall architecture of the OCT
      images with a reasonable diagnostic accuracy when used in combination.

PMID- 19159386
TI  - Topically applied growth factors change skin cytoplasmic creatine kinase activity
      and distribution and produce abnormal keratinocyte differentiation in murine
      skin.
AB  - BACKGROUND/PURPOSE: The skin has a functional and active phosphocreatine
      (PCR)/creatine kinase (CPK) system that regenerates adenosine triphosphate energy
      reserves during periods of ischemia. The objective of this study was to evaluate
      how topically applied growth factors affect CPK activity and distribution, and
      what histological changes growth factors induce in murine skin. METHODS:
      Epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) and
      suramin (growth factor inhibitor) were applied to murine skin for nine days
      before mice were sacrificed and CPK level and distributions were measured.
      RESULTS: TGF-alpha considerably increased CPK activity. Both EGF and TGF-alpha
      induced a CPK MM to CPK BB transition and histologically induced abnormal
      differentiation of keratinocytes. CONCLUSION: The skin PCR/CPK system is affected
      by growth factors. Furthermore, this system appears to play an important role,
      both in the normal physiology of skin and pathophysiological conditions such as
      psoriasis and carcinogenesis.

PMID- 19159387
TI  - In vitro antioxidant activity and in vivo efficacy of topical formulations
      containing vitamin C and its derivatives studied by non-invasive methods.
AB  - BACKGROUND/PURPOSE: Vitamins C and its derivatives, mainly due to their
      antioxidant properties, are being used in cosmetic products to protect and to
      reduce the signs of ageing. However, there are no studies comparing the effects
      of vitamin C [ascorbic acid (AA)] and its derivatives, magnesium ascorbyl
      phosphate (MAP) and ascorbyl tetra-isopalmitate (ATIP), when vehiculated in
      topical formulations, mainly using objective measurements, which are an important
      tool in clinical efficacy studies. Thus, the objective of this study was to
      determine the in vitro antioxidant activity of AA and its derivatives, MAP and
      ATIP, as well as their in vivo efficacy on human skin, when vehiculated in
      topical formulations. METHODS: The study of antioxidant activity in vitro was
      performed with an aqueous and a lipid system. The in vivo methodology consisted
      of the application of these formulations on human volunteers' forearm skin and
      the analysis of the skin conditions after 4-week period daily applications in
      terms of transepidermal water loss (TEWL), stratum corneum moisture content and
      viscoelasticity using a Tewameter, Corneometer and Cutometer, respectively.
      RESULTS: In vitro experiments demonstrated that in an aqueous system, AA had the
      best antioxidant potential, and MAP was more effective than ATIP, whereas in the
      lipid system ATIP was more effective than MAP. In in vivo studies, all
      formulations enhanced stratum corneum moisture content after a 4-week period
      daily applications when compared with baseline values; however, only the
      formulation containing AA caused alterations in TEWL values. The formulations
      containing MAP caused alterations in the viscoelastic-to-elastic ratio, which
      suggested its action in the deeper layers of the skin. CONCLUSION: AA and its
      derivates presented an in vitro antioxidant activity but AA had the best
      antioxidant effect. In in vivo efficacy studies, only the formulation containing
      AA caused alterations in TEWL values and the formulation containing MAP caused
      alterations in the viscoelastic-to-elastic ratio. This way, vitamin C derivatives
      did not present the same effects of AA on human skin; however, MAP showed other
      significant effect-improving skin hydration, which is very important for the
      normal cutaneous metabolism and also to prevent skin alterations and early
      ageing.

PMID- 19159388
TI  - beta-arrestins attenuate p38-mediated endosome to Golgi transport.
AB  - Shiga toxin (Stx) is after endocytosis transported via early endosomes to the
      Golgi apparatus and endoplasmic reticulum. It is then translocated to the cytosol
      where it exerts its toxic effect. We recently reported that p38 is required for
      endosome to Golgi transport of Stx. In the present study, we investigated whether
      beta-arrestins are effectors of this pathway. beta-arrestin knockdown led to
      enhanced Stx transport. A similar phenotype was achieved upon p38 activation. We
      demonstrate that p38 and beta-arrestin act on the same pathway. beta-arrestin
      colocalized with internalized Stx and, interestingly, was recruited to endosomes
      upon p38 activation. After Stx treatment, p38 and beta-arrestin formed a
      transient complex. From these data we propose that beta-arrestin negatively
      regulates Stx transport via an interaction with activated p38 and attenuation of
      its signalling. Interestingly, also mannose 6-phosphate receptor transport was
      regulated by p38 and beta-arrestin. beta-arrestins therefore seem to regulate an
      endosome to Golgi pathway used by multiple cargo proteins.

PMID- 19159389
TI  - Cyclophilin A facilitates translocation of the Clostridium botulinum C2 toxin
      across membranes of acidified endosomes into the cytosol of mammalian cells.
AB  - The binary Clostridium botulinum C2 toxin consists of the binding/translocation
      component C2IIa and the separate enzyme component C2I, which mono-ADP-ribosylates
      actin in eukaryotic cells. Pore formation of C2IIa in early endosomal membranes
      facilitates translocation of unfolded C2I into the cytosol. We discovered earlier
      that translocation of C2I depends on the activity of the host cell chaperone heat
      shock protein Hsp90. Here, we demonstrate that cyclosporin A, which inhibits the
      peptidyl-prolyl cis/trans isomerase activity of cyclophilins, inhibited
      intoxication of cells with C2 toxin and prevented uptake of C2I into the cytosol.
      Cyclosporin A blocked the pH-dependent translocation of C2I activity across
      membranes of intact cells and of partially purified early endosomes. In vitro,
      the addition of cytosol to C2 toxin-loaded endosomes induced translocation of C2I
      activity into the cytosol, which was prevented by pretreatment of the cytosol
      with an antibody against cyclophilin A. Pull-down experiments with lysates from
      C2 toxin-treated cells revealed specific binding of cyclophilin A to the N
      terminal domain of C2I. In conclusion, our results suggest an essential role of
      cyclophilin A for translocation of C2I across endosomal membranes during the
      uptake of C2 toxin into mammalian cells.

PMID- 19159390
TI  - A protein secreted by the respiratory pathogen Chlamydia pneumoniae impairs IL-17
      signalling via interaction with human Act1.
AB  - Chlamydia pneumoniae is a common respiratory pathogen that has been associated
      with a variety of chronic diseases including asthma and atherosclerosis.
      Chlamydiae are obligate intracellular parasites that primarily infect epithelial
      cells where they develop within a membrane-bound vacuole, termed an inclusion.
      Interactions between the microorganism and eukaryotic cell can be mediated by
      chlamydial proteins inserted into the inclusion membrane. We describe here a
      novel C. pneumoniae-specific inclusion membrane protein (Inc) CP0236, which
      contains domains exposed to the host cytoplasm. We demonstrate that, in a yeast
      two-hybrid screen, CP0236 interacts with the NFkappaB activator 1 (Act1) and this
      interaction was confirmed in HeLa 229 cells where ectopically expressed CP0236
      was co-immunoprecipitated with endogenous Act1. Furthermore, we demonstrate that
      Act1 displays an altered distribution in the cytoplasm of HeLa cells infected
      with C. pneumoniae where it associates with the chlamydial inclusion membrane.
      This sequestration of Act1 by chlamydiae inhibited recruitment of the protein to
      the interleukin-17 (IL-17) receptor upon stimulation of C. pneumoniae-infected
      cells with IL-17A. Such inhibition of the IL-17 signalling pathway led to
      protection of Chlamydia-infected cells from NFkappaB activation in IL-17
      stimulated cells. We describe here a unique strategy employed by C. pneumoniae to
      achieve inhibition of NFkappaB activation via interaction of CP0236 with
      mammalian Act1.

PMID- 19159392
TI  - A novel autosomal dominant deafness locus (DFNA58) maps to 2p12-p21.

PMID- 19159393
TI  - Clinical and genetic analysis of the CHD7 gene in Korean patients with CHARGE
      syndrome.

PMID- 19159391
TI  - Noncoding RNAs in mental retardation.
AB  - Recent genome-wide interrogations of transcribed RNA have yielded compelling
      evidence for pervasive and complex transcription throughout a large majority of
      the human genome. Tens of thousands of noncoding RNA transcripts have been
      identified, most of which have yet to be functionally characterized. Along with
      the revelation that noncoding RNAs in the human genome are surprisingly abundant,
      there has been a surge in molecular and genetic data showing important and
      diverse regulatory roles for noncoding RNA. In this report, we summarize the
      potential roles that noncoding RNAs may play in the molecular pathogenesis of
      different mental retardation disorders. We suspect that these findings are just
      the tip of the iceberg, with noncoding RNAs possibly being involved in disease
      pathogenesis at different levels and through multiple distinct mechanisms.

PMID- 19159394
TI  - Prevalence of dural ectasia in 63 gene-mutation-positive patients with features
      of Marfan syndrome type 1 and Loeys-Dietz syndrome and report of 22 novel FBN1
      mutations.
AB  - Marfan syndrome is an autosomal dominant disorder involving different organ
      systems. Marfan syndrome type 1 (MFS1) is caused by mutations in the FBN1 gene.
      Heterozygosity for mutations in the TGFBR1 or TGFBR2 genes cause Loeys-Dietz
      syndrome (LDS) types 2A and 2B that overlap with MFS1 in their clinical features.
      The phenotype of MFS1 is defined by the Ghent nosology, which classifies the
      clinical manifestations in major and minor criteria. Dural ectasia is one of the
      major criteria for Marfan syndrome but it is rarely tested for. We here report 22
      novel and 9 recurrent mutations in the FBN1 gene in 36 patients with clinical
      features of Marfan syndrome. Sixty patients with identified mutations in the FBN1
      gene and three patients with mutations in the TGFBR1 or TGFBR2 genes were
      examined for dural ectasia. Forty-seven of the 60 patients (78%) with MFS1 showed
      the dural ectasia criterion and 13 (22%) did not. Thirty-three (55%) patients
      were suspected of having Marfan syndrome and 24 (73%) of them had dural ectasia.
      Two of the three patients with LDS had dural ectasia.

PMID- 19159395
TI  - Sister chromatid exchange and micronucleus studies in patients with Behcet's
      disease.
AB  - BACKGROUND: Genetic factors that predispose individuals to Behcet's disease (BD)
      are considered to play important roles in the development of the disease. The aim
      of this study was to determine, by counting sister chromatid exchange (SCE) and
      micronucleus (MN) frequencies, whether DNA damage have an effect on the
      pathogenesis of BD. Furthermore, our aim was to show if there is an association
      between oxidative stress and chromosome instability in BD. METHODS: We analyzed
      lymphocytes from patients with BD (16 in active and 14 in inactive periods) and
      20 healthy controls for SCE and MN frequencies. In addition, malondialdehyde
      (MDA) level, superoxide dismutase (SOD) level, glutathione peroxidase (GSH-Px)
      activity, erythrocyte sedimentation rate (ESR) and polymorphonuclear leukocyte
      (PMNL) count were determined in the all subjects. RESULTS: The SCE and MN
      frequencies were significantly higher in both the active and inactive period
      patients than in the controls (p < 0.00001, p < 0.0001, p < 0.01 and p < 0.05,
      respectively), and the MDA level was significantly higher in both the active and
      inactive period patients than in the controls (p < 0.01 and p < 0.05,
      respectively). In contrast, the SOD and GSH-Px levels were significantly lower in
      both the active and inactive period patients than in the controls (p < 0.01, p <
      0.05, p < 0.01 and p < 0.05, respectively). CONCLUSIONS: Our results suggest that
      increased plasma MDA level and decreased plasma GSH-Px and SOD levels reflect the
      increased levels of oxidative stress in BD patients, and this situation may
      impair genetic stability in BD patients.

PMID- 19159396
TI  - Infertility, infertility treatment and psychomotor development: the Danish
      National Birth Cohort.
AB  - Babies born of infertile couples, regardless of treatment, have a higher risk of
      preterm birth and low birthweight, conditions associated with delayed
      development. We examined developmental milestones in singletons as a function of
      parental infertility [time to pregnancy (TTP) > 12 months] and infertility
      treatment. From the Danish National Birth Cohort (1997-2003), we identified 37
      897 singletons born of fertile couples (TTP < or = 12 months), 4351 born of
      infertile couples conceiving naturally (TTP > 12 months), and 3309 born after
      infertility treatment. When the children were about 18 months old, mothers
      reported 12 developmental milestones by responding to structured questions. We
      defined a failure to achieve the assessed milestone or the minimal numbers of
      milestones in a summary (motor, or cognitive/language skills) as delay. Naturally
      conceived children born of infertile couples had a pattern of psychomotor
      development similar to that of children born of fertile couples, but increasing
      TTP correlated with a modest delay. When the analysis was restricted to infertile
      couples (treated and untreated), children born after treatment showed a slight
      delay in cognitive/language development (odds ratio 1.24, [95% confidence
      interval 1.01, 1.53]) for not meeting at least three out of six
      cognitive/language milestones); children born after intracytoplasmic sperm
      injection (ICSI) had the highest estimated relative risk of delay for most
      milestones, especially motor milestones. These results suggest that a long TTP
      may be associated with a modest developmental delay. Infertility treatment,
      especially ICSI, may be associated with a slight delay for some of these early
      milestones.

PMID- 19159397
TI  - Consanguinity and reproductive wastage in the Palestinian Territories.
AB  - Many studies have found that consanguinity poses a threat to child mortality and
      health and can also pose a threat to offspring survival before birth. However,
      there are conflicting findings with some studies having found no increased risk
      on offspring survival associated with consanguinity. Data from a population-based
      survey conducted in 2004 in the Palestinian Territories was used to assess the
      risk of consanguinity on offspring survival. The analysis was conducted on 4418
      women aged 15-49 who were asked whether or not they had experienced a stillbirth
      or a spontaneous abortion. These two outcomes were combined together for the
      analysis of reproductive wastage. Multivariable negative binomial regression was
      conducted to calculate the incidence risk ratios (IRR) for each region in the
      Palestinian Territories separately. The strongest risk factors for reproductive
      wastage, after controlling for other variables, were found to be consanguinity,
      age and parity with age presenting the highest IRRs. Standard of living, locality
      type, education level, women's employment and past intrauterine device use were
      not found to be significant risk factors for reproductive wastage. In the West
      Bank only first cousin level of consanguinity was found to be significant and
      'hamola' level (or from same family clan) lost its significance after adjusting
      for other variables. In the Gaza Strip both the first cousin and 'hamola' levels
      of consanguinity were significant and presented almost equal IRRs of 1.3. In
      conclusion, consanguinity was found to be a significant risk factor for
      reproductive wastage.

PMID- 19159399
TI  - The epidemiology of neuroblastoma: a review.
AB  - Neuroblastoma is the most common tumour in children less than 1 year of age. The
      goal of this review was to summarise the existing epidemiological research on
      risk factors for neuroblastoma. A comprehensive search of the literature was
      undertaken using PubMed for epidemiological studies on neuroblastoma risk
      factors. We ascertained 47 articles which examined the risk factors. Ten studies
      employed population-based case-control designs; six were hospital-based case
      control studies; two were cohort studies; and five employed ecological designs.
      Studies ranged in size from 42 to 538 cases. Three studies showed evidence of an
      increased risk of disease with use of alcohol during pregnancy (OR range 1.1,
      12.0). Protective effects were seen with maternal vitamin intake during pregnancy
      (OR range 0.5, 0.7) in two studies, while risk of disease increased with maternal
      intake of diuretics (OR range 1.2, 5.8) in three studies. Three studies reported
      a decrease in risk for children with a history of allergic disease prior to
      neuroblastoma diagnosis (OR range 0.2, 0.4). The rarity of neuroblastoma makes
      this disease particularly challenging to study epidemiologically. We review the
      methodological limitations of prior research and make suggestions for further
      areas of study.

PMID- 19159398
TI  - Neural tube defects: an analysis of neighbourhood- and individual-level socio
      economic characteristics.
AB  - Several studies have reported that neural tube defects (NTD) occur more
      frequently among children born to women of lower socio-economic status (SES).
      This study investigated the relationship between individual- and neighbourhood
      level SES and the risk of an NTD-affected pregnancy. Data were drawn from a
      population-based case-control study of fetuses and infants among a cohort of
      California births between July 1999 and June 2003. Information on individual SES
      was obtained via telephone interviews with mothers of 337 (76% of eligible) cases
      and 626 (79% of eligible) non-malformed liveborn controls. Respondents' addresses
      were linked to the 2000 US Census to characterise six measures of neighbourhood
      SES (education, poverty, unemployment, occupation, crowding and rental
      occupancy). The analyses indicated that relative to women with a high school
      education, those with less than a high school education had a 1.7-fold increased
      risk of delivering infants with NTDs [95% CI 1.2, 2.6]. Twofold elevated risks
      for NTDs were observed for women with less than a high school education who lived
      in neighbourhoods where a majority of residents had not graduated from high
      school [95% CI 1.3, 3.1]. No consistent risk gradients were observed between NTD
      affected pregnancies and indicators of lower neighbourhood SES. Results for
      phenotype subgroups were similar to those for all cases. Low maternal education
      was associated with an elevated risk of NTD in offspring. This risk varied by the
      education profile of the neighbourhood: women who did not graduate from high
      school and lived in less educated neighbourhoods exhibited a higher risk.

PMID- 19159400
TI  - Monitoring the quality of maternity care: how well are labour and delivery events
      reported in population health data?
AB  - Administrative or population health data sets (PHDS), such as birth and hospital
      discharge data, are used increasingly to evaluate maternity care. Use of PHDS
      requires reliable identification of diagnoses and procedures. The aim of this
      study was to determine the accuracy and reliability of the reporting of diagnoses
      and procedures related to childbirth in both individual and linked, birth and
      ICD10-coded hospital discharge data. Data from a population-based validation
      study of 1200 women provided the 'gold standard' for labour and delivery events
      and were compared with the hospital discharge and birth databases. Reporting
      characteristics (sensitivity, specificity, positive and negative predictive
      values) were determined for: induction, augmentation and obstruction of labour,
      modes of delivery (including failed instrumental delivery), episiotomy, perineal
      tears and repairs, and manual removal of the placenta. Differences in reporting
      by mode of delivery were also examined. Of the 1184 records available for review,
      25% had labour induced, 25% had labour augmented and, of those who laboured, 17%
      had obstructed labour reported. Fourteen per cent had an elective/planned
      caesarean section (CS) including 2% that went into labour prior to the planned
      date, and 11% had an emergency, unplanned CS including 2% who had no labour. With
      the exception of augmentation and obstruction of labour, failed instrumental
      delivery and manual removal, there were high levels of accuracy for reporting of
      diagnoses and procedures during labour and delivery. There were no significant
      differences in reporting by mode of delivery. The findings suggest that PHDS
      reported induction of labour, mode of delivery, and 3rd and 4th degree tears and
      repairs can be reliably used to evaluate maternity care. Consistency in reporting
      in birth and hospital discharge data from different countries and over time
      suggests the findings are likely to be generalisable to high-income countries.

PMID- 19159401
TI  - Risk factors for croup in children with recurrent respiratory infections: a case
      control study.
AB  - Croup accounts for approximately 15% of all lower respiratory disease in
      children, but little is known about risk factors or its recurrence rate. The aim
      of this study was to determine the risk factors for croup and recurrent croup and
      to find out whether it is possible to predict the course of the disease. We
      considered croup patients who visited the Paediatric Department of Oulu
      University Hospital as primary health care patients at night during 1996-2000.
      For most analyses we used sex- and age-matched control patients who had had other
      respiratory infection but for environmental factors we used population controls.
      We performed conditional logistic regression analysis on data applying to 182
      pairs of patients and controls. The recurrence rate was high, as 61% of the croup
      patients had had at least three episodes. Family history of croup was the most
      significant risk factor for both croup itself and recurrent croup. In
      multivariable analysis the odds ratio (OR) for the parents having a history of
      croup was 3.2 (95% CI 1.5, 7.1, P < 0.01) and 4.1 (95% CI 1.4, 11.7, P < 0.01)
      for recurrent croup. Parental smoking appeared to be a risk factor for
      respiratory infections but not for croup. Patients with croup had a cat as a pet
      less often than the controls, with OR 0.5 (95% CI 0.2, 1.0, P = 0.04). Family
      history appeared to be an exceptionally strong predictive factor for croup and
      its recurrence. In this patient series prone to respiratory infections recurrence
      of croup was common.

PMID- 19159402
TI  - The complex enterprise of modelling prenatal exposure to cigarettes: what is
      'enough'?
AB  - While there is a burgeoning body of research linking smoking during pregnancy to
      problem behaviour in offspring, a major criticism of this work has been the crude
      measurement of exposure in these studies (e.g. retrospective, self-reported only)
      that could lead to biased estimates. To address this issue, we used a pregnancy
      cohort with repeated prospective measures of exposure as well as biological
      assays to generate estimates of exposure patterns using a range of modelling
      techniques. In this paper we report on the analytical approaches we have
      developed, including patterns of exposure over time and best-estimate approaches
      that combine self-report and cotinine measures, and compare their predictive
      value in relation to different dimensions of fetal growth as a first step towards
      examining the utility of greater precision of exposure measurement. Surprisingly,
      in this sample the more complex assessments of exposure, including biological
      measures, generally did not perform better than simple indicators of exposure
      based on repeated self-report measures, with one exception: a combined self
      report cotinine 'best estimate' of third trimester exposure was uniquely
      associated with lower brain : body ratio. Further study is needed using more
      sophisticated cotinine assays and testing prediction of a range of outcomes to
      ascertain whether these findings represent true differences or are specific to
      the sample, methods and outcomes used. Such research will inform the development
      of guidelines for adequate exposure characterisation in developmental studies.

PMID- 19159403
TI  - BioCycle study: design of the longitudinal study of the oxidative stress and
      hormone variation during the menstrual cycle.
AB  - Studies in both human and animal species have suggested that oxidative stress may
      be associated with health outcomes, including the risk of infertility in both
      males and females. Sex hormones have been shown to have antioxidant properties.
      The difficulty in studying the role of oxidative stress in females is partly due
      to fluctuation in these endogenous sex hormones across the menstrual cycle. The
      aim of this study was to determine the association of oxidative stress levels
      with endogenous reproductive hormone levels and antioxidants, including vitamin
      levels, across the menstrual cycle in a prospective cohort of premenopausal
      women. The goal was to enroll 250 healthy, regularly menstruating premenopausal
      women for two menstrual cycles. Participants visited the clinic up to 8 times per
      cycle, at which time blood and urine were collected. The visits occurred at key
      hormonally defined phases of the menstrual cycle, with the help of an algorithm
      based on cycle length and data from a fertility monitor. In addition,
      participants were administered standardised questionnaires, had various physical
      measures taken, and had other pertinent data collected. A total of 259 women were
      enrolled in this study, with 250 completing two cycles, despite a demanding study
      protocol which participants were required to follow. This report describes the
      study design, baseline characteristics and visit completion rate for the BioCycle
      study.

PMID- 19159404
TI  - Fast food consumption counters the protective effect of breastfeeding on asthma
      in children?
AB  - BACKGROUND: Fast food consumption and childhood asthma have rapidly increased in
      recent decades. During the same period there has been an increased rate of
      prolonged breastfeeding. OBJECTIVE: To evaluate if fast food consumption was
      associated with asthma in children, and if the proposed protective effect of
      breastfeeding on asthma was altered by fast food consumption. METHODS: This case
      control study included 246 children with allergist-diagnosed asthma and 477 non
      asthmatic controls at age 8-10 years. Information on fast food consumption and
      exclusive breastfeeding was obtained from questionnaire data. The association
      between asthma and fast food consumption was evaluated. Asthma in relation to
      exclusive breastfeeding was also evaluated, taking into account fast food
      consumption as a modifying factor. RESULTS: Children with asthma were more likely
      to consume fast food than children without asthma [crude odds ratio (OR) 1.70,
      95% confidence interval (CI) 1.23-2.34]. In comparison to prolonged exclusive
      breastfeeding (> or =12 weeks), asthma was positively associated with short-term
      exclusive breastfeeding (<12 weeks) in children who never or occasionally
      consumed fast food (crude OR 1.84, 95% CI 1.09-3.11), but not in children who
      frequently consumed fast food (crude OR 1.07, 95% CI 0.72-1.61). The P-value for
      this interaction (0.109) was borderline. Children with high fast food consumption
      who were exclusively breastfed <12 weeks as infants, had greater than a twofold
      risk of asthma compared with infants who had been exclusively breastfed for a
      longer time period and who did not become high consumers of fast food in later
      childhood. These findings were not affected after final adjustment of confounders
      and covariates. CONCLUSION: Fast food consumption is associated with asthma in
      children and potentially counteracts the protective effect of prolonged
      breastfeeding on asthma. This may explain the paradoxical phenomenon of parallel
      increased rates of prolonged breastfeeding and asthma in children. 556-561.

PMID- 19159405
TI  - Activation of muscarinic receptors elicits inotropic responses in ventricular
      muscle from rats with heart failure through myosin light chain phosphorylation.
AB  - BACKGROUND AND PURPOSE: Muscarinic stimulation increases myofilament Ca(2+)
      sensitivity with no apparent inotropic response in normal rat myocardium.
      Increased myofilament Ca(2+) sensitivity is a molecular mechanism promoting
      increased contractility in failing cardiac tissue. Thus, muscarinic receptor
      activation could elicit inotropic responses in ventricular myocardium from rats
      with heart failure, through increasing phosphorylation of myosin light chain
      (MLC). EXPERIMENTAL APPROACH: Contractile force was measured in left ventricular
      papillary muscles from male Wistar rats, 6 weeks after left coronary artery
      ligation or sham surgery. Muscles were also frozen, and MLC-2 phosphorylation
      level was quantified. KEY RESULTS: Carbachol (10 micromol.L(-1)) evoked a
      positive inotropic response only in muscles from rats with heart failure
      approximating 36% of that elicited by 1 micromol.L(-1) isoproterenol (20 +/- 1.5%
      and 56 +/- 6.1% above basal respectively). Carbachol-evoked inotropic responses
      did not correlate with infarction size but did correlate with increased left
      ventricular end diastolic pressure, heart weight/body weight ratio and lung
      weight, primary indicators of the severity of heart failure. Only muscarinic
      receptor antagonists selective for M(2) receptors antagonized carbachol-mediated
      inotropic effects with the expected potency. Carbachol-evoked inotropic responses
      and increase in phosphorylated MLC-2 were attenuated by MLC kinase (ML-9) and Rho
      kinase inhibition (Y-27632), and inotropic responses were abolished by Pertussis
      toxin pretreatment. CONCLUSION AND IMPLICATIONS: In failing ventricular muscle,
      muscarinic receptor activation, most likely via M(2) receptors, provides
      inotropic support by increasing MLC phosphorylation and consequently, myofilament
      Ca(2+) sensitivity. Enhancement of myofilament Ca(2+) sensitivity, representing a
      less energy-demanding mechanism of inotropic support may be particularly
      advantageous in failing hearts.

PMID- 19159406
TI  - Oxycodone is associated with dose-dependent QTc prolongation in patients and low
      affinity inhibiting of hERG activity in vitro.
AB  - WHAT IS ALREADY KNOWN: During recent years some opioids have been associated with
      prolonged QT and torsade de pointes (TdP). In vitro testing has shown that most
      opioids can block the cardiac potassium channels. This indicates that QT
      prolongation and TdP could be a more general problem associated with the use of
      these drugs. WHAT THIS PAPER ADDS: This study is the first to show that oxycodone
      dose is associated with QT prolongation and in vitro blockade of hERG channels
      expressed in HEK293. Neither morphine nor tramadol doses are associated with the
      QT interval length. AIMS: During recent years some opioids have been associated
      with prolonged QT interval and torsade de pointes (TdP). In vitro patch clamp
      testing has shown that most opioids can block human ether-a-go-go related gene
      (hERG) channels that are known to underlie cardiac repolarizing I(Kr) current.
      This indicates that QT prolongation and TdP could be a more general problem
      associated with the use of these drugs. The aims of this study were to evaluate
      the association between different opioids and the QTc among patients and measure
      hERG activity under influence by opioids in vitro. METHODS: One hundred chronic
      nonmalignant pain patients treated with methadone, oxycodone, morphine or
      tramadol were recruited in a cross-sectional study. The QTc was estimated from a
      12-lead ECG. To examine hERG activity in the presence of oxycodone,
      electrophysiological testing was conducted using Xenopus laevis oocytes and
      HEK293 cells expressing hERG channels. RESULTS: There were no differences in
      gender distribution or age between the treatment groups. The known association
      between methadone dose and QTc was confirmed (R(2) = 0.09; P = 0.02). Higher
      oxycodone dose was also associated with longer QTc (R(2) = 0.21; P = 0.02). A 100
      mg higher oxycodone dose was associated with a 10 ms(1/2) (95% CI 2-19) longer
      QTc. Neither morphine nor tramadol dose was associated with the QTc.
      Electrophysiological testing revealed low-affinity inhibition of the potassium
      current through hERG channels expressed in HEK293 cells (IC(50) = 171 microM
      oxycodone). CONCLUSIONS: Among patients treated with methadone or oxycodone,
      higher doses were associated with longer QTc. Oxycodone is capable of inhibiting
      hERG channels in vitro.

PMID- 19159407
TI  - Genetic mapping of the belt pattern in Brown Swiss cattle to BTA3.
AB  - The white belt pattern of Brown Swiss cattle is characterized by a lack of
      melanocytes in a stretch of skin around the midsection. This pattern is of
      variable width and sometimes the belt does not fully circle the body. To identify
      the gene responsible for this colour variation, we performed linkage mapping of
      the belted locus using six segregating half-sib families including 104
      informative meioses for the belted character. The pedigree confirmed a monogenic
      autosomal dominant inheritance of the belted phenotype in Brown Swiss cattle. We
      performed a genome scan using 186 microsatellite markers in a subset of 88
      animals of the six families. Linkage with the belt phenotype was detected at the
      telomeric region of BTA3. Fine-mapping and haplotype analysis using 19 additional
      markers in this region refined the critical region of the belted locus to a 922
      kb interval on BTA3. As the corresponding human and mouse chromosome segments
      contain no obvious candidate gene for this coat colour trait, the mutation
      causing the belt pattern in the Brown Swiss cattle might help to identify an
      unknown gene influencing skin pigmentation.

PMID- 19159408
TI  - A second cycle of tamsulosin in patients with distal ureteric stones: a
      prospective randomized trial.
AB  - OBJECTIVE: To evaluate, in a prospective randomized pilot study, the
      effectiveness and safety of tamsulosin, administered in patients with distal
      ureteric stones and who have already undergone an unsuccessful first cycle of
      medical expulsive therapy (MET). PATIENTS AND METHODS: We evaluated the
      effectiveness and safety of tamsulosin, administered as a further therapy, in
      patients previously unsuccessfully treated with combined expulsive 10-day therapy
      (tamsulosin + deflazacort) for distal ureteric stones. Ninety-one patients were
      enrolled and randomized into two groups, each receiving a different therapy for
      10 days. Group A (46 patients) received a further cycle of tamsulosin (0.4 mg
      daily), and group B (45) did not. Age, gender, stone size, time to expulsion,
      number of acute episodes of colic during treatment and analgesic consumption were
      recorded. Patients who were not stone-free after the study period had
      ureteroscopy. The results were compared statistically using Student's t-, chi
      square test and Fisher's exact test. RESULTS: The groups were comparable in age,
      gender and stone size (5.93 mm for group A and 6.03 mm for group B). The
      expulsion rate was significantly higher in group A (80%) than in group B (49%) (P
      < 0.01), whilst there were no differences between the groups in the number of
      colic episodes and analgesic use. There were no reported side-effects of medical
      therapy. CONCLUSIONS: A second cycle of 10 days of MET with tamsulosin in
      nonresponders to a 10-day first cycle of MET with tamsulosin and deflazacort is
      safe and effective, and therefore should be considered as an option in the
      management of uncomplicated distal ureteric stones.

PMID- 19159409
TI  - Low-frequency extracorporeal shock wave lithotripsy improves renal pelvic stone
      disintegration in a pig model.
AB  - OBJECTIVE: To compare disintegration rates for renal stones treated by 60 vs 120
      shock waves (SW)/min at the same energy settings, using standardized validated
      artificial stones in a pig model. MATERIALS AND METHODS: Gypsum artificial stones
      (13 x 6 mm) were inserted into the renal pelvis on either side of 12
      anaesthetized pigs by open surgery. Extracorporeal SW lithotripsy (ESWL) was
      applied using a new electromagnetic lithotripter (Lithoskop, Siemens AG
      Healthcare, Munich, Germany) at 60 and 120 SW/min; 3000 SW were applied to each
      kidney with the same energy settings. Stone fragments were collected after
      nephrectomy, passed through calibrated test sieves, and weighed. Fragment size
      categories were stratified according to the sieve hole size as set by the
      manufacturer. Fragments of < or =4.75 mm were defined as capable of spontaneous
      passage. For each pig the number of stone fragments of the respective size
      categories was counted and weighed. The results were analysed statistically using
      the Mann-Whitney U-test. RESULTS: For fragments of >4.75 mm, the median (range)
      fragment counts were 0 (0-1) for 60 and 1 (0-3) for 120 SW/min (P = 0.006). For
      small fragments of 2.0-2.8 mm, the median fragment counts were 15 (4-24) for 60
      and 10 (2-25) for 120 SW/min (P = 0.033); for fragments of 1.0-2.0 mm the
      respective values were 42.5 (9-81) and 21.5 (6-56) (P = 0.004). Of the total
      stone fragment mass in the 60 and 120 SW/min groups, 4.34% and 31.31% were >4.75
      mm. There was complete disintegration yielding fragments capable of spontaneous
      passage in 10 of 12 renal units at 60 and in three of 12 renal units at 120
      SW/min. The mean treatment time was 55.4 min for therapy at 60 and 34.3 min for
      therapy at 120 SW/min (P = 0.001). One parenchymal haematoma of 15 x 10 mm
      developed in the 60 SW/min group and another of 20 x 10 mm developed in the 120
      SW/min group. CONCLUSION: ESWL fragmentation with equal energy application yields
      significantly smaller fragments at 60 than at 120 SW/min. The theoretical stone
      passage rate could therefore be approximately 80% for 60 vs 25% for 120 SW/min
      ESWL. Renal haematoma formation was comparable in both groups.

PMID- 19159410
TI  - Diesel oil-induced alopecia in two cats.
AB  - Two cats were presented for acute onset of rapidly progressive, bilaterally
      symmetrical hair loss of the ventrum and limbs. Alopecia occurred within 2 weeks
      after accidental skin exposure to diesel oil. The remaining hair epilated easily
      in affected areas. Denuded skin was strikingly dry and had adherent scale.
      Erythema and demarcation between affected and normal skin by a liquid-line were
      present in one case. Above this line, the hair could not be removed. The head and
      the footpads were not involved. Systemic signs were not observed. Both cats made
      a complete recovery without treatment. Histological examination in one cat
      revealed severe orthokeratotic hyperkeratosis, mild to moderate acanthosis,
      follicular keratosis, a moderate dermal infiltrate of mast cells and an almost
      complete absence of sebaceous glands. If skin contact with diesel oil occurs in a
      cat, thorough washing of skin and haircoat after soaking in prue vegetable oil is
      recommended.

PMID- 19159411
TI  - Cutaneous fungal granuloma in a horse.
AB  - This case report describes a 4-year-old-horse with two cutaneous masses on the
      right crest of the neck. Biopsy revealed chronic nodular pyogranulomatous
      dermatitis and panniculitis. Giemsa and periodic acid-Schiff stains showed focal
      spherical, yeast-like organisms. A diagnosis of cutaneous fungal granuloma was
      made. The size of the masses decreased after oral treatment with fluconazole for
      10 days combined with potassium iodide for 30 days, and the remaining masses were
      excised by laser. Lesions did not recur at the site. Fungal granuloma should be
      considered as a differential diagnosis in horses with cutaneous or subcutaneous
      nodules. A definitive diagnosis can only be achieved by histopathological
      examination or by culture of the affected tissue.

PMID- 19159412
TI  - Investigation of the pruritogenic effects of histamine, serotonin, tryptase,
      substance P and interleukin-2 in healthy dogs.
AB  - There are numerous studies of the pruritus-producing effects of histamine,
      serotonin, tryptase, substance P and interleukin-2 in humans and mice, but very
      little reported in dogs even though a common reason dogs are presented to
      veterinarians is pruritus. The aim of this study was to determine whether
      substances known to cause pruritus in humans also cause pruritus in dogs. Twenty
      five clinically healthy research beagle dogs were included in the study. All dogs
      first received an intradermal injection of 0.05 mL saline as a control substance
      and were video-recorded for 20 min before and after the injection. Twenty-four
      hours later the dogs were randomly divided into five groups of five dogs each and
      randomly assigned to receive histamine, serotonin, tryptase, substance P or
      interleukin-2 injected intradermally each at the volume of 0.05 mL. On subsequent
      days, increasing concentrations of each substance were used. Before (baseline)
      and after the injection of each concentration of the substances, the dogs were
      video-recorded for 20 min. The frequency and character of pruritus episodes
      (scratching, licking, chewing, rubbing or rolling) were noted and these data were
      used for statistical analysis. The number of pruritus episodes was compared among
      baseline, saline and the different concentrations of each substance. The results
      showed that dogs did not have a significant increase in pruritic behaviour above
      baseline or saline after injection of any of the investigated substances
      (generalized linear model; P = 0.23).

PMID- 19159413
TI  - Curative effect of autologous platelet-rich plasma on a large cutaneous lesion in
      a dog.
AB  - A dorsal tail mass (1 x 1.2 cm) was observed on a 10-year-old castrated male,
      Shih-tzu dog. A biopsy of the mass was performed and diagnosed
      histopathologically as a follicular cyst. A necrotic lesion (2.5 x 3 cm)
      developed at the biopsy site 1 week after sampling and failed to respond to 2
      weeks of normal saline cleansing and systemic antibiotic administration.
      Autologous platelet-rich plasma was applied to the lesion which gradually
      improved over a 4-week period possibly by a contribution to the secretion of
      growth hormone, which can accelerate tissue regeneration. This case report
      suggests that autologous PRP may be beneficial in the management of large skin
      defects or in delayed wound healing.

PMID- 19159414
TI  - Confirmatory factor analysis and sample invariance of the Chinese Patient
      Satisfaction Questionnaire (ChPSQ-9) among patients with breast and lung cancer.
AB  - OBJECTIVES: Previous exploratory factor analysis of the 9-item Chinese Patient
      Satisfaction Questionnaire (ChPSQ-9) identified two dominant factors: doctor and
      nurse. The present study employed confirmatory factor analysis (CFA) to examine
      the factorial invariance of the ChPSQ-9 between and within samples of Chinese
      patients with breast or lung cancer. METHODS: Longitudinal data were analyzed
      from Chinese breast and lung cancer patients who had completed the ChPSQ-9 during
      their first outpatient visit, at 3 months, and at 6 months after baseline. CFAs
      tested the fit of a one-factor model, a hierarchical model that comprised a
      general latent factor and two first-order factors, and a correlated model that
      comprised two correlated first-order factors to the data. The factorial
      invariance of the ChPSQ-9 between six independent samples across time was
      investigated using multigroup CFAs. RESULTS: The CFA's results demonstrated a
      better fit of the correlated model over the one-factor model and the hierarchical
      model in the breast and lung cancer samples. The correlated model showed evidence
      of cross-sample and longitudinal factorial invariance. Patients were generally
      satisfied with services provided by doctors and nurses. Internal consistency of
      the scale was also good for both cancer samples across time. CONCLUSIONS: The
      ChPSQ-9 is a valid and reliable instrument to be employed among breast and lung
      cancer patients, in clinical settings or intervention research, to evaluate group
      differences in patient satisfaction and its association with intervention
      effectiveness.

PMID- 19159415
TI  - High-resolution HLA matching in double-umbilical-cord-blood reduced-intensity
      transplantation in adults.
AB  - BACKGROUND: Double-cord-blood transplantation (DCBT) offers an option for
      patients receiving reduced-intensity transplants. These unique transplants have
      two donors, both of whom are usually HLA mismatched at one to two loci. STUDY
      DESIGN AND METHODS: Fifty-three patients were recipients of a reduced-intensity
      DCBT. Cords were at least 4/6 allele-level HLA-A, -B, and -DR match with the
      patient and each other with a minimum combined cell dose of more than 3.7 x 10(7)
      total nucleated cells per kg. Twenty-one patients received
      cyclosporine/mycophenolate mofetil and 32 patients received sirolimus/tacrolimus
      (SIR/TAC) for graft-versus-host disease prophylaxis. The effect of allele level
      HLA typing on clinical endpoints of overall survival (OS), disease-free survival
      (DFS), engraftment, and acute graft-versus-host disease (aGVHD) were assessed.
      RESULTS: Neutrophil (p = 0.001) engraftment and platelet engraftment (p = 0.027)
      were significantly faster in patients who have closer Class I (HLA-A, -B, -C)
      matching. Neutrophil engraftment was faster in patients who had closer HLA-B
      matching to their combined cords (p = 0.007). There was a low incidence of aGVHD
      overall, especially in the SIR/TAC group. Class I HLA matching had no effect on
      aGVHD. HLA-DR and -DQ had no effect on engraftment or aGVHD. CONCLUSION: Class I
      allele matching, and HLA-B matching specifically, were associated with faster
      neutrophil engraftment. High-resolution HLA matching did not affect OS or DFS.

PMID- 19159416
TI  - Activity of clotting factors in fresh-frozen plasma during storage at 4 degrees C
      over 6 days.
AB  - BACKGROUND: Fresh-frozen plasma (FFP) requires thawing, which delays
      availability. We investigated clotting factor activity and bacterial
      contamination of FFP when stored at 4 degrees C +/- 2 degrees C for 6 days. STUDY
      DESIGN AND METHODS: Plasma of 20 healthy plasma donors was sampled, frozen, and
      analyzed at baseline and repeatedly over a period of 6 days after thawing. The
      activity of fibrinogen, Factor (F)II, FV, FVII, FVIII, F IX, FX, XI, FXII, FXIII,
      antithrombin III (ATIII), von Willebrand factor antigen (VWF-Ag), protein C (PC),
      and free protein S (FPS) were determined and analyzed over time. RESULTS:
      Immediately after thawing there was a significant decrease of fibrinogen (-9%),
      FII (-7%), FV (-14%), FVII (-12%), FX (-11%), FXIII (-20%), PC (-7%), and ATIII (
      4%), whereas FVIII (+8%), F IX (+1%), FXI (+11%), FXII (-1%), FPS (-1%), and VWF
      Ag (-6%) remained stable without significant change. Over 6 days after thawing
      fibrinogen, ATIII (+2%) and VWF-Ag (+2%) remained stable whereas FXII (+2%),
      FXIII (+6%), and PC (+3%) changed significantly over time and increased at the
      end. FII (-8%), FV (-16%), FVII (-31%), FVIII (-47%), F IX (-12%), FX (-10%), FXI
      (-25%), and FPS (+/-0%) changed also significantly over time and decreased at the
      end. All clotting factors and inhibitors remained within the reference range
      requested by quality assurance regulations. No FFP bag showed bacterial
      contamination. CONCLUSION: This provides evidence for maintaining quality of
      thawed FFP and may improve rapid availability in emergency situations and reduce
      cost for health care givers.

PMID- 19159417
TI  - Leuconostoc septicemia in a neutropenic patient with acute myelogenous leukemia
      relapsed after allogeneic peripheral blood stem cell transplantation.

PMID- 19159418
TI  - Extended storage of whole blood before the preparation of blood components: in
      vitro effects on red blood cells in Erythro-Sol environment.
AB  - BACKGROUND AND OBJECTIVES: Routine procedures for extended storage of whole blood
      (WB) before the preparation of blood components are of interest primarily for
      logistical reasons. We stored red cell units in either Erythro-Sol 2 (E-Sol 2,
      test units, 150 ml added) or in saline-adenine-glucose-mannitol (SAG-M)
      (reference units, 100 ml added) that were prepared after storage of WB at room
      temperature for 8, 12, 16 or 19 h after blood collection. STUDY DESIGN AND
      METHODS: Red blood cells were stored for 42 days. We measured pH, glucose,
      lactate, haemolysis, red blood cell adenosine triphosphate and 2,3
      diphosphoglycerate on days 1, 7, 14, 21, 28, 35 and 42. RESULTS: Haematocrits
      were significantly lower in E-Sol 2 than in SAG-M due to the higher volume of E
      Sol 2 added compared to SAG-M. Significantly reduced levels were found in E-Sol 2
      of extracellular pH (throughout storage after 8-h hold and initially after 12-,
      16- or 19-h hold), of lactate (initially after 8-h hold and throughout storage
      after 12-, 16- or 19-h hold), and of haemolysis from day 35 in the 8-h and on day
      42 in the 12-h hold group. Significantly increased levels of adenosine
      triphosphate were seen in E-Sol 2 after 8-h hold (from day 14) and after 12-h
      hold (at days 21, 35 and 42) compared to SAG-M. Significantly higher
      concentrations of 2,3-diphosphoglycerate were noticed primarily after 8-h hold of
      WB. CONCLUSION: The use of E-Sol 2 as a replacement for SAG-M does not
      significantly improve in vitro data after extended storage of WB at room
      temperature before preparation of blood components. However, after 8-h hold in
      vitro characteristics similar to or better than in fresh blood will be maintained
      for several weeks in E-Sol 2, a situation that makes E-Sol 2 superior to SAG-M
      when storage of WB is limited to 8 h. Some improvement was noted after 12-h hold
      as well.

PMID- 19159419
TI  - Evidence of heterogeneity in the antibody response against the platelet antigen
      3a; recognition of an 11-mer peptide carrying the HPA-3a polymorphic determinant.
AB  - BACKGROUND: The immune processes involved in the development of alloantibodies
      against the human platelet antigens in alloimmune disorders remain unclear.
      Antibody recognition of the platelet antigens on their respective platelet
      glycoproteins has been shown to be dependent on glycoprotein conformation.
      Furthermore, the post-translational modification of glycoproteins adds complexity
      to the alloantigenic determinants. METHODS: Nine anti-HPA-3a sera along with
      several control sera were tested for reactivity to an 11-mer peptide straddling
      the HPA-3a/b polymorphism. Sera found to specifically recognize the 3a peptide
      were further assessed by platelet pre-exposure and immunoblotting. RESULTS: Three
      of the nine antisera were found to specifically recognize an 11-mer synthetic 3a
      peptide by ELISA. Further analysis of all anti-HPA-3a sera by Western blot showed
      that only those reactive to the 3a peptide were able to bind both reduced and non
      reduced GPIIb. CONCLUSION: The results presented in this study provide the first
      known evidence for the identification of an antibody population capable of
      recognizing a linear and non-glycosylated form of the HPA-3a epitope.

PMID- 19159420
TI  - Multiple physiological states of a Pseudomonas fluorescens DR54 biocontrol
      inoculant monitored by a new flow cytometry protocol.
AB  - A new fluorescence staining and flow cytometry protocol was developed to monitor
      several physiological states in biocontrol strain Pseudomonas fluorescens DR54
      during storage survival in a stationary-phase culture, preparation of clay
      carrier for seed formulation, and establishment in a sugar beet spermosphere. The
      high load of impurities in the environmental samples was dealt with by adding a
      density-gradient purification step to the staining protocol. Staining by SYBR
      Green, combined with either propidium iodide or ethidium bromide
      (EB)+DiBAC((4))3, was used to quantify the total cell population and further
      divide this population into: (1) intact cells with an unaffected membrane and
      energy metabolism. (2) De-energized cells unable to maintain membrane export (EB
      exclusion). (3) Depolarized cells unable to maintain membrane potential. (4)
      Permeabilized cells with a damaged membrane. During both stationary-phase storage
      and steps for preparation of formulation carrier, loss of intact P. fluorescens
      DR54 cells was quantitatively accounted for by depolarized and permeabilized
      states. Surviving inoculum cells subsequently proliferated on the germinating
      seeds, but with a surprisingly high abundance of de-energized cells. The new
      protocol is the first for flow cytometry to include a recording of both intact
      and several subpopulations of physiologically affected bacteria in complex,
      environmental samples with high impurity loads.

PMID- 19159421
TI  - High turnover of fungal hyphae in incubation experiments.
AB  - Soil biological studies are often conducted on sieved soils without the presence
      of plants. However, soil fungi build delicate mycelial networks, often
      symbiotically associated with plant roots (mycorrhizal fungi). We hypothesized
      that as a result of sieving and incubating without plants, the total fungal
      biomass decreases. To test this, we conducted three incubation experiments. We
      expected total and arbuscular mycorrhizal (AM) fungal biomass to be higher in
      less fertilized soils than in fertilized soils, and thus to decrease more during
      incubation. Indeed, we found that fungal biomass decreased rapidly in the less
      fertilized soils. A shift towards thicker hyphae occurred, and the fraction of
      septate hyphae increased. However, analyses of phospholipid fatty acids (PLFAs)
      and neutral lipid fatty acids could not clarify which fungal groups were
      decreasing. We propose that in our soils, there was a fraction of fungal biomass
      that was sensitive to fertilization and disturbance (sieving, followed by
      incubation without plants) with a very high turnover (possibly composed of fine
      hyphae of AM and saprotrophic fungi), and a fraction that was much less
      vulnerable with a low turnover (composed of saprotrophic fungi and runner hyphae
      of AMF). Furthermore, PLFAs might not be as sensitive in detecting changes in
      fungal biomass as previously thought.

PMID- 19159422
TI  - Response of arctic snow and permafrost algae to high light and nitrogen stress by
      changes in pigment composition and applied aspects for biotechnology.
AB  - Ten algal strains from snow and permafrost substrates were tested for their
      ability to produce secondary carotenoids and alpha-tocopherol in response to high
      light and decreased nitrogen levels. The Culture Collection of Cryophilic Algae
      at Fraunhofer IBMT in Potsdam served as the bioresource for this study. Eight of
      the strains belong to the Chlorophyceae and two strains are affiliated to the
      Trebouxiophyceae. While under low light, all 10 strains produced the normal
      spectrum of primary pigments known to be present in Chlorophyta, only the eight
      chlorophyceaen strains were able to synthesize secondary carotenoids under stress
      conditions, namely canthaxanthin, echinenone and astaxanthin; seven of them were
      also able to synthesize minor amounts of adonixanthin and an unidentified
      hydroxyechinenone. The two trebouxiophyceaen species of Raphidonema exhibited an
      unusually high pool of primary xanthophyll cycle pigments, possibly serving as a
      buffering reservoir against excessive irradiation. They also proved to be good
      alpha-tocopherol producers, which might also support the deactivation of reactive
      oxygen species. This study showed that some strains might be interesting novel
      candidates for biotechnological applications. Cold-adapted, snow and permafrost
      algae might serve as valuable production strains still exhibiting acceptable
      growth rates during the cold season in temperate regions.

PMID- 19159423
TI  - Comparison of microbial communities associated with phase-separation-induced
      hydrothermal fluids at the Yonaguni Knoll IV hydrothermal field, the Southern
      Okinawa Trough.
AB  - Microbial communities associated with a variety of hydrothermal emissions at the
      Yonaguni Knoll IV hydrothermal field, the southernmost Okinawa Trough, were
      analyzed by culture-dependent and -independent techniques. In this hydrothermal
      field, dozens of vent sites hosting physically and chemically distinct
      hydrothermal fluids were observed. Variability in the gas content and formation
      in the hydrothermal fluids was observed and could be controlled by the potential
      subseafloor phase-separation and -partition processes. The hydrogen concentration
      in the hydrothermal fluids was also variable (0.8-3.6 mmol kg(-1)) among the
      chimney sites, but was unusually high as compared with those in other Okinawa
      Trough hydrothermal fields. Despite the physical and chemical variabilities of
      the hydrothermal fluids, the microbial communities were relatively similar among
      the habitats. Based on both culture-dependent and -independent analyses of the
      microbial community structures, members of Thermococcales, Methanococcales and
      Desulfurococcales likely represent the predominant archaeal components, while
      members of Nautiliaceae and Thioreductoraceae are considered to dominate the
      bacterial population. Most of the abundant microbial components appear to be
      chemolithotrophs sustained by hydrogen oxidation. The relatively consistent
      microbial communities found in this study could have been because of the
      sufficient input of hydrogen from the hydrothermal fluids rather than other
      chemical properties.

PMID- 19159424
TI  - Considerations on Chlamydia trachomatis disease expression.
AB  - Chlamydia disease expression is the result of complex molecular and cellular
      interactions between the host and a pathogen which appears to have been sculpted
      by evolutionary forces. Recent genomic, immunologic, and epidemiologic findings
      are reviewed. A synthesis is offered which suggests that Chlamydia disease
      expression results from persistent infection and host immune responses.

PMID- 19159425
TI  - Immunological surrogate marker of rAls3p-N vaccine-induced protection against
      Staphylococcus aureus.

PMID- 19159426
TI  - Determination of chlamydial load and immune parameters in asymptomatic,
      symptomatic and infertile women.
AB  - The regulation of immune response and chlamydial infectious load in the cervix of
      human females is largely unknown. Infectious load in terms of inclusion-forming
      units (IFUs) was determined by quantitative cultures in Chlamydia-positive women,
      in asymptomatic women, women with mucopurulent cervicitis (MPC) and women with
      fertility disorders (FD). CD4(+), CD8(+), CD14(+) cells, myeloid and plasmacytoid
      dendritic cells (mDCs and pDCs) in the cervix were quantified by flow cytometry.
      Cervical cytokines, levels of beta-estradiol and C-reactive protein (CRP) in
      serum and cervical immunoglobulin A antibody to chlamydial major outer membrane
      protein antigen, chlamydial heat shock protein 60 and 10 antigens were measured
      by an enzyme-linked immunosorbent assay. In asymptomatic women, chlamydial load
      showed significant positive correlations with CD4, mDCs, interleukin-12 (IL-12)
      and IL-2; however, negative correlations were found with CD8 and IL-8 levels. In
      women with MPC, chlamydial IFUs correlated positively with CD8, pDC number, IL-8,
      CRP and interferon-gamma (IFN-gamma). In women with FD, chlamydial load showed a
      significant positive correlation with the pDC number, IL-10 and estradiol level
      and a negative correlation with CD4 and IFN-gamma. Overall, these results suggest
      that the interplay between chlamydial infectious load and host immune responses
      may be the deciding factor for the clinical condition presented during Chlamydia
      trachomatis infection.

PMID- 19159427
TI  - Cellular response induced by a galactose-specific adhesin of enteroaggregative
      Escherichia coli in INT-407 cells.
AB  - In the present study, the role of a fimbrial galactose-specific adhesin of the T7
      strain of enteroaggregative Escherichia coli (EAEC-T7) in the signal transduction
      pathways in human small intestinal epithelial cells (INT-407) was explored. The
      adhesin was purified by anion exchange chromatography using a Mono Q HR5/5 column
      in the AKTA purifier system. The characteristic stacked brick pattern of
      aggregative adherence of EAEC-T7 to INT-407 cells was found to be inhibited in
      the presence of immunoglobulin G against the purified adhesin as well as d
      galactose. The adhesin induced a significant increase in the intracellular
      calcium concentration [Ca(2+)](i) in INT-407 cells, which was reduced in the
      presence of dantrolene (inhibitor of intracellular calcium stores), verapamil,
      calciseptin (calcium channel blockers) as well as neomycin [inhibitor of
      phospholipase C (PLC)]. Further, an increased level of PLCgamma1 and inositol
      1,4,5-tri phosphate as well as enhanced activity of protein kinase C (PKC) in the
      adhesin-stimulated cells were found to be downregulated in the presence of
      neomycin and U73122 (inhibitors of PLC) and H-7 (inhibitor of PKC), respectively.
      The adhesin could also induce interleukin-8 secretion from INT-407 cells, which
      was inhibited in the presence of dantrolene as well as staurosporin (inhibitor of
      PKC). Collectively, our results have suggested that the galactose-specific
      adhesin-induced signal transduction pathway might play a crucial role in the EAEC
      induced pathogenesis.

PMID- 19159428
TI  - Blockade of epithelial membrane protein 2 (EMP2) abrogates infection of Chlamydia
      muridarum murine genital infection model.
AB  - New methods are needed to eradicate or prevent Chlamydia trachomatis infections.
      Blockade of epithelial membrane protein 2 (EMP2) by genetic silencing or
      neutralizing polyclonal antibody reduced chlamydial infectivity in vitro. This
      study tests the prediction that recombinant anti-EMP2 diabody could reduce early
      chlamydial infection of the genital tract in vivo. In a murine infection model,
      pretreatment with anti-EMP2 diabody, as compared with control diabody,
      significantly reduced bacterial load, tissue production of inflammatory
      cytokines, recruitment of polymorphonuclear leukocytes, and local tissue
      inflammation. These findings support EMP2 as a potential preventative and
      therapeutic target for genital chlamydial infection.

PMID- 19159429
TI  - Detection and frequency of Chlamydia trachomatis DNA in synovial samples from
      Tunisian patients with reactive arthritis and undifferentiated oligoarthritis.
AB  - We aimed to determine the frequency of Chlamydia trachomatis DNA in the synovial
      compartment of 34 arthritic patients. Chlamydia trachomatis DNA was detected
      using a nested PCR targeting the cryptic plasmid, the 16S rRNA gene and the outer
      membrane protein 1 gene. The presence of serum immunoglobulin (Ig)G and IgA
      antibodies against C. trachomatis was studied by a microimmunofluorescence assay
      and by an enzyme-linked immunosorbent assay, respectively. Synovial samples from
      20 of 34 (59%) patients [nine with reactive arthritis (ReA), seven with
      undifferentiated oligoarthritis (UOA), two with rheumatoid arthritis and two with
      osteoarthritis] were positive for at least one C. trachomatis DNA sequence by
      nested PCR. The high sensitivity results most likely from the combination of a
      standardized automated MagNA Pure extraction method, PCR targeting three
      different C. trachomatis genes and the screening for C. trachomatis in synovial
      tissue and fluid samples. There was no correlation between the presence of C.
      trachomatis DNA in the joint and a Chlamydia-specific serologic response. Our
      data support that PCR is the method of choice to establish the diagnosis of
      Chlamydia-induced arthritis in patients with ReA. We suggest that this diagnosis
      might also be considered in C. trachomatis-positive patients previously
      classified as UOA.

PMID- 19159430
TI  - Identification of dendritic cell subsets responding to genital infection by
      Chlamydia muridarum.
AB  - Dendritic cells (DCs) are central for the induction of T-cell responses needed
      for chlamydial eradication. Here, we report the activation of two DC subsets: a
      classical CD11b+ (cDC) and plasmacytoid (pDC) during genital infection with
      Chlamydia muridarum. Genital infection induced an influx of cDC and pDC into the
      genital tract and its draining lymph node (iliac lymph nodes, ILN) as well as
      colocalization with T cells in the ILN. Genital infection with C. muridarum also
      stimulated high levels of costimulatory molecules on cDC central for the
      activation of naive T cells in vivo. In contrast, pDC expressed low levels of
      most costimulatory molecules in vivo and did not secrete cytokines associated
      with the production of T helper (Th)1 cells in vitro. However, pDC upregulated
      inducible costimulatory ligand expression and produced IL-6 and IL-10 in response
      to chlamydial exposure in vitro. Our findings show that these two DC subsets
      likely have different functions in vivo. cDCs are prepared for induction of
      antichlamydial T-cell responses, whereas pDCs have characteristics associated
      with the differentiation of non-Th1 cell subsets.

PMID- 19159432
TI  - Differential upregulation of chemokine receptors on CD56 NK cells and their
      transmigration to the site of infection in tuberculous pleurisy.
AB  - Chemokines and their receptors orchestrate leukocyte recruitment and confer
      immunity during Mycobacterium tuberculosis infection. The immunoregulatory and
      cytotoxic activities of natural killer (NK) cells are essential at the site of
      infection during tuberculous pleurisy. The frequency, subtypes, and expression of
      phenotype markers and chemokine receptors on NK cells were assessed by flow
      cytometry in tuberculous (TB) and nontuberculous (NTB) pleural fluid (PF).
      Chemotaxis was also shown in response to chemokines. A significant decrease in
      CD56(dim) with no change in CD56(bright) NK cells was observed, while a
      significant increase in activation markers and Toll-like receptors (TLRs) was
      observed on TB-PF CD56(bright) NK cells. Significantly increased expression of
      chemokine receptors CCR1, CCR2 and CCR7 on CD56(bright) and CCR5 on CD56(dim) NK
      cells was observed in the TB group. Transmigration of TB-PF NK cells was
      significantly high in response to IL-8, IP-10, MCP-1 and SLC. Transmigrated TB-NK
      cells showed a significant increase in CXCR2, CCR2 and CCR7 expression. The study
      suggests that CD56(bright) NK cells may recognize M. tuberculosis directly using
      TLRs, HLA-DR and express CD69 as an early activation marker. In addition, CC
      chemokines induce activation signals in chemokine receptors mediating
      differential NK cell migration to the site. Thus, NK cells act as first direct
      sensors and effectors in mycobacterial infection.

PMID- 19159431
TI  - PapR peptide maturation: role of the NprB protease in Bacillus cereus 569
      PlcR/PapR global gene regulation.
AB  - The global transcriptional regulator PlcR controls gene expression in Bacillus
      cereus and Bacillus thuringiensis. Activity of PlcR is regulated by PapR, the
      product of an ORF located immediately downstream of plcR. To be active in B.
      cereus, PapR must be secreted and then processed to the mature peptide by an
      unknown protease. This peptide is transported by an oligopeptide permease into
      the cell, where it activates PlcR. In this study, we show that the neutral
      protease B (NprB) secreted by B. cereus 569 is required for extracellular PapR
      maturation. Purified recombinant NprB processed the synthetic PapR propeptide to
      produce a set of peptides derived from the C-terminal domain of PapR.
      Supplementation of growth media with synthetic PapR-derived C-terminal 5-, 7-, 8-
      and 27-amino acid (aa) peptides caused activation of intracellular PlcR in a PapR
      deficient strain of B. cereus 569 while only the 5- and 7-aa peptides activated
      PlcR in a nprB mutant. The maximum activity was found for the 7-mer peptide.
      However, even the 7-mer peptide could not activate PlcR with a C-terminal
      truncation of as few as 6 aa. This indicates that interactions of the C-terminal
      regions of both PlcR and PapR are important in transcriptional activation of the
      B. cereus 569 PlcR regulon.

PMID- 19159433
TI  - Innate immunity and vaccines in chlamydial infection with special emphasis on
      Chlamydia pneumoniae.
AB  - Chlamydial infections are prevalent worldwide. Immunological events related to
      both innate and adaptive immunity during chlamydial infection can aid in recovery
      from the disease, but they can also cause harmful effects (immunopathology). The
      host genetic factors (variation in innate immunity and adaptive response-related
      genes) can predispose individuals to infection and its sequelae as well as
      determine the effects of intervention. No effective vaccine is available for
      human use. Modern technologies and data obtained using different 'omics'
      techniques (genomics, proteomics, transcriptomics and immunomics) might help in
      designing novel, more efficient vaccines, hopefully also against chlamydial
      infections.

PMID- 19159434
TI  - The genus Dietzia: a new home for some known and emerging opportunist pathogens.
AB  - The genus Dietzia has only been established fairly recently. The Gram morphology
      and colony appearance of the species of this genus is remarkably similar to
      Rhodococcus equi. In the absence of simple, accurate methods for their
      identification, Dietzia spp. might have been misidentified as a Rhodococcus spp.
      and/or considered to be contaminants only. This MiniReview is designed to
      summarize current evidence on the clinical significance of Dietzia species, to
      consider their potential role as human pathogens, and to outline approaches that
      can be used to accurately classify and identify members of the genus, with the
      overall aim of alerting the medical microbiological community to a little known
      genus that contains clinically significant organisms.

PMID- 19159435
TI  - Differential effect of imatinib and synergism of combination treatment with
      chemotherapeutic agents in malignant glioma cells.
AB  - Imatinib mesylate (STI571, Gleevec) is a signal transduction inhibitor and novel
      anti-cancer agent. It selectively inhibits aberrantly activated tyrosine kinases
      in malignant cells, for example, bcr-abl in leukaemia, platelet-derived growth
      factor receptor and stem cell factor receptor (c-Kit) in solid cancers including
      malignant glioma. However, recently published clinical studies with imatinib
      monotherapy in patients with malignant glioma demonstrated only very modest anti
      tumour activity. The aim of this study was to investigate the biological activity
      of imatinib, its cellular mechanisms of action and its synergism with other
      chemotherapeutic agents in human malignant glioma cells in culture. Expression of
      PDGF/R and c-Kit was analyzed by RT-PCR. Proliferation was measured by MTT assays
      and drug synergy was assessed by the Chou-Talalay method. Cell cycle and
      apoptosis were analyzed by flow cytometry and migration by monolayer migration
      assays. Multi-immunoblot was performed on imatinib-treated and control malignant
      glioma cells. Results indicate that imatinib is more effective in inhibiting cell
      colony formation and migration rather than proliferation. Imatinib treatment
      caused cell cycle arrest of glioma cells in G0-G1 or G2/M, with significant
      elevation of a few cyclin-dependent kinases. Furthermore, imatinib acted
      synergistically with chemotherapy agents, such as the DNA alkylating agent,
      temozolomide, and riboneucleotide reductase inhibitors, for example, hydroxyurea
      at varied effective dose levels. In conclusion, imatinib exerts varied biological
      effects on malignant glioma cells in culture. Synergistic interaction of imatinib
      with chemotherapy agents may be related to cell cycle control mechanisms and
      could be potentially important in a clinical setting.

PMID- 19159436
TI  - Effects of niacin on cell adhesion and early atherogenesis: biochemical and
      functional findings in endothelial cells.
AB  - Atherosclerotic cardiovascular disease is a major cause of morbidity and
      mortality. Increased expression of cell adhesion molecules (CAM) and their
      ligands mediate essential processes in atherogenesis. Niacin reduces
      atherosclerotic cardiovascular complications and total mortality. Further
      understanding is needed on effects of niacin on CAM, and its functional
      consequences. The aim of this study was to evaluate the effects of niacin on CAM
      expression and monocyte adhesion in endothelial cells. Endothelial cells (HUVEC)
      were cultured to reach 80-90% confluence before experiments were initiated. Cells
      were exposed to DME/F12 with selected concentrations of niacin. To elicit the
      expression of CAM, cells were stimulated by addition of tumour necrosis factor
      (TNF)-alpha, interleukin (IL)-1 or interferon-gamma. Lysate from the conditioned
      media was assayed for CAM. The effect of niacin on mRNA expression of ICAM-1 was
      studied using semi-quantitative analysis of ICAM-1 mRNA. Adhesion assays were
      performed with flow cytometry to study the functional significance of the effects
      niacin on CAM expression. Niacin significantly reduced ICAM-1 and PECAM-1 protein
      levels basally, and reduced the cytokine-induced rise in ICAM-1, with a similar
      effect for TNF-alpha-induced PECAM-1 rise. The decrease in TNF-alpha-induced rise
      in ICAM-1 level was associated with a reduction of NF-kappaB activation, a
      reduction in mRNA expression of ICAM-1, and a functional reduction in monocyte
      adhesion to cultured endothelial cells. Niacin reduces CAM expression and
      monocyte adhesion to endothelial cells. Apart from its lipid-modifying effects,
      these pleiotropic effects of niacin may potentially contribute to the beneficial
      effects of risk reduction for atherosclerotic disease.

PMID- 19159437
TI  - Age and gender specific normal values of left ventricular mass, volume and
      function for gradient echo magnetic resonance imaging: a cross sectional study.
AB  - BACKGROUND: Knowledge about age-specific normal values for left ventricular mass
      (LVM), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV)
      and ejection fraction (EF) by cardiac magnetic resonance imaging (CMR) is of
      importance to differentiate between health and disease and to assess the severity
      of disease. The aims of the study were to determine age and gender specific
      normal reference values and to explore the normal physiological variation of
      these parameters from adolescence to late adulthood, in a cross sectional study.
      METHODS: Gradient echo CMR was performed at 1.5 T in 96 healthy volunteers (11-81
      years, 50 male). Gender-specific analysis of parameters was undertaken in both
      absolute values and adjusted for body surface area (BSA). RESULTS: Age and gender
      specific normal ranges for LV volumes, mass and function are presented from the
      second through the eighth decade of life. LVM, ESV and EDV rose during
      adolescence and declined in adulthood. SV and EF decreased with age. Compared to
      adult females, adult males had higher BSA-adjusted values of EDV (p = 0.006) and
      ESV (p < 0.001), similar SV (p = 0.51) and lower EF (p = 0.014). No gender
      differences were seen in the youngest, 11-15 year, age range. CONCLUSION: LV
      volumes, mass and function vary over a broad age range in healthy individuals. LV
      volumes and mass both rise in adolescence and decline with age. EF showed a rapid
      decline in adolescence compared to changes throughout adulthood. These findings
      demonstrate the need for age and gender specific normal ranges for clinical use.

PMID- 19159439
TI  - Hepatic artery aneurysm repair: a case report.
AB  - INTRODUCTION: Hepatic artery aneurysms remain a clinically significant entity.
      Their incidence continues to rise slowly and mortality from spontaneous rupture
      is high. Repair is recommended in those aneurysms greater than 2 cm in diameter.
      It is not surprising that vascular comorbidities, such as ischaemic heart
      disease, are common in surgical patients, particularly those with arterial
      aneurysms such as these. The decision of when to operate on patients who require
      urgent surgery despite having recently suffered an acute coronary syndrome
      remains somewhat of a grey and controversial area. We discuss the role of delayed
      surgery and postoperative followup of this vascular problem. CASE PRESENTATION: A
      58-year-old man was admitted with a 5.5 cm hepatic artery aneurysm. The aneurysm
      was asymptomatic and was an incidental finding as a result of an abdominal
      computed tomography scan to investigate an episode of haemoptysis (Figure 1).
      Three weeks prior to admission, the patient had suffered a large inferior
      myocardial infarction and was treated by thrombolysis and primary coronary
      angioplasty. Angiographic assessment revealed a large aneurysm of the common
      hepatic artery involving the origins of the hepatic, gastroduodenal, left and
      right gastric arteries and the splenic artery (Figures 2 and 3). Endovascular
      treatment was not considered feasible and immediate surgery was too high-risk in
      the early post-infarction period. Therefore, surgery was delayed for 3 months
      when aneurysm repair with reconstruction of the hepatic artery was successfully
      performed. Graft patency was confirmed with the aid of an abdominal arterial
      duplex. Plasma levels of conventional liver function enzymes and of alpha
      glutathione-S-transferase were within normal limits. This was used to assess the
      extent of any hepatocellular damage perioperatively. The patient made a good
      recovery and was well at his routine outpatient check-ups. CONCLUSION: There is
      no significant difference in cardiac risk in patients who have undergone vascular
      surgery within 6 months of a myocardial infarction compared with those who have
      had the operation in the 6 to12 month time frame. Use of alpha-glutathione-S
      transferase gives an indication of the immediate state of hepatic function and
      should be used in addition to traditional liver function tests to monitor hepatic
      function postoperatively.

PMID- 19159438
TI  - When is a GIST not a GIST? A case report of synchronous metastatic
      gastrointestinal stromal tumor and fibromatosis.
AB  - BACKGROUND: A number of non-malignant diseases that share similar morphological
      features as gastrointestinal stromal tumor (GIST) have been reported. Co
      existence of GIST with these other diseases is rarely recognized or reported.
      CASE PRESENTATION: We report a case of a 62 year-old man with long-term stable
      control of metastatic GIST with systemic therapy, presented with an apparent
      intra-abdominal progression but not supported by imaging with positron emission
      tomography. Subsequent resection of the intra-abdominal tumor identified a non
      malignant fibroid. CONCLUSION: Differentiating localized progression of GIST from
      other diseases has important prognostic and therapeutic implications. The
      potential for co-existence of non-malignant soft tissue neoplasm should always be
      considered.

PMID- 19159440
TI  - Cutaneous metastases of breast carcinoma: a case report.
AB  - BACKGROUND: Cutaneous metastases can have variable clinical appearances and can
      mimic benign skin lesions. They are usually seen in patients with advanced
      disease, but they can be the presenting lesion. CASE PRESENTATION: A 48-year-old
      woman presented with a 3-month history of progressive appearance of multiple
      asymptomatic nodular lesions on the chest. The recognition of cutaneous
      metastases often dramatically alters therapeutic plans, especially when
      metastases signify persistence of cancer originally thought to be cured. The most
      common tumor to metastasize to the skin is breast cancer. CONCLUSION: Every
      practitioner should be highly suspicious of acute-onset, persistent, firm
      papulonodules, especially when they develop on the chest.

PMID- 19159441
TI  - Infliximab for the treatment of intravenous immunoglobulin resistant Kawasaki
      disease complicated by coronary artery aneurysms: a case report.
AB  - This case report describes an 8 year old boy with IVIG resistant Kawasaki
      disease complicated by severe bilateral coronary artery aneurysms successfully
      treated with infliximab, a monoclonal antibody against tumour necrosis factor
      alpha.

PMID- 19159442
TI  - A rare case of cardiac paraganglioma presenting as anginal pain: a case report.
AB  - INTRODUCTION: Primary cardiac paraganglioma is a very rare tumor with less than
      sixty reported cases in the literature. The clinical presentation is variable,
      but is most commonly manifested by hypertension and symptoms related to the
      catecholamine excess. CASE REPORT: We report a case of a 35 year old man who
      presented with anginal pain and hypertension. He was found to have a cardiac mass
      on the computed tomographic scan and echocardiogram. He underwent surgical
      exploration of the mass which on biopsy was found to be a 'Cardiac
      Paraganglioma'. Surgical resection of the tumor was successfully done and the
      patient is doing well five years after the surgery without any evidence of
      recurrence. His blood pressure, however, failed to normalize and needed single
      agent antihypertensive therapy. CONCLUSION: Cardiac paragangliomas have a
      relatively favorable outcome if diagnosed and resected in time. We briefly review
      the literature regarding the diagnosis, treatment and prognosis of this rare
      tumor.

PMID- 19159443
TI  - Measuring inequalities in the distribution of health workers: the case of
      Tanzania.
AB  - BACKGROUND: The overall human resource shortages and the distributional
      inequalities in the health workforce in many developing countries are well
      acknowledged. However, little has been done to measure the degree of inequality
      systematically. Moreover, few attempts have been made to analyse the implications
      of using alternative measures of health care needs in the measurement of health
      workforce distributional inequalities. Most studies have implicitly relied on
      population levels as the only criterion for measuring health care needs. This
      paper attempts to achieve two objectives. First, it describes and measures health
      worker distributional inequalities in Tanzania on a per capita basis; second, it
      suggests and applies additional health care needs indicators in the measurement
      of distributional inequalities. METHODS: We plotted Lorenz and concentration
      curves to illustrate graphically the distribution of the total health workforce
      and the cadre-specific (skill mix) distributions. Alternative indicators of
      health care needs were illustrated by concentration curves. Inequalities were
      measured by calculating Gini and concentration indices. RESULTS: There are
      significant inequalities in the distribution of health workers per capita.
      Overall, the population quintile with the fewest health workers per capita
      accounts for only 8% of all health workers, while the quintile with the most
      health workers accounts for 46%. Inequality is perceptible across both urban and
      rural districts. Skill mix inequalities are also large. Districts with a small
      share of the health workforce (relative to their population levels have an even
      smaller share of highly trained medical personnel. A small share of highly
      trained personnel is compensated by a larger share of clinical officers (a middle
      level cadre) but not by a larger share of untrained health workers. Clinical
      officers are relatively equally distributed. Distributional inequalities tend to
      be more pronounced when under-five deaths are used as an indicator of health care
      needs. Conversely, if health care needs are measured by HIV prevalence, the
      distributional inequalities appear to decline. CONCLUSION: The measure of
      inequality in the distribution of the health workforce may depend strongly on the
      underlying measure of health care needs. In cases of a non-uniform distribution
      of health care needs across geographical areas, other measures of health care
      needs than population levels may have to be developed in order to ensure a more
      meaningful measurement of distributional inequalities of the health workforce.

PMID- 19159444
TI  - Should applicants to Nottingham University Medical School study a non-science A
      level? A cohort study.
AB  - BACKGROUND: It has been suggested that studying non-science subjects at A-level
      should be compulsory for medical students. Our admissions criteria specify only
      Biology, Chemistry and one or more additional subjects. This study aimed to
      determine whether studying a non-science subject for A-level is an independent
      predictor of achievement on the undergraduate medical course. METHODS: The
      subjects of this retrospective cohort study were 164 students from one entry-year
      group (October 2000), who progressed normally on the 5-year undergraduate medical
      course at Nottingham. Pre-admission academic and socio-demographic data and
      undergraduate course marks were obtained. T-test and hierarchical multiple linear
      regression analyses were undertaken to identify independent predictors of five
      course outcomes at different stages throughout the course. RESULTS: There was no
      evidence that the choice of science or non-science as the third or fourth A-level
      subject had any influence on course performance. Demographic variables (age
      group, sex, and fee status) had some predictive value but ethnicity did not. Pre
      clinical course performance was the strongest predictor in the clinical phases
      (pre-clinical Themes A&B (knowledge) predicted Clinical Knowledge, p < 0.001, and
      pre-clinical Themes C&D (skills) predicted Clinical Skills, p = or< 0.01).
      CONCLUSION: This study of one year group at Nottingham Medical School provided no
      evidence that the admissions policy on A-level requirements should specify the
      choice of third or fourth subject.

PMID- 19159445
TI  - Towards Web-based representation and processing of health information.
AB  - BACKGROUND: There is great concern within health surveillance, on how to grapple
      with environmental degradation, rapid urbanization, population mobility and
      growth. The Internet has emerged as an efficient way to share health information,
      enabling users to access and understand data at their fingertips. Increasingly
      complex problems in the health field require increasingly sophisticated computer
      software, distributed computing power, and standardized data sharing. To address
      this need, Web-based mapping is now emerging as an important tool to enable
      health practitioners, policy makers, and the public to understand spatial health
      risks, population health trends and vulnerabilities. Today several web-based
      health applications generate dynamic maps; however, for people to fully interpret
      the maps they need data source description and the method used in the data
      analysis or statistical modeling. For the representation of health information
      through Web-mapping applications, there still lacks a standard format to
      accommodate all fixed (such as location) and variable (such as age, gender,
      health outcome, etc) indicators in the representation of health information.
      Furthermore, net-centric computing has not been adequately applied to support
      flexible health data processing and mapping online. RESULTS: The authors of this
      study designed a HEalth Representation XML (HERXML) schema that consists of the
      semantic (e.g., health activity description, the data sources description, the
      statistical methodology used for analysis), geometric, and cartographical
      representations of health data. A case study has been carried on the development
      of web application and services within the Canadian Geospatial Data
      Infrastructure (CGDI) framework for community health programs of the New
      Brunswick Lung Association. This study facilitated the online processing, mapping
      and sharing of health information, with the use of HERXML and Open Geospatial
      Consortium (OGC) services. It brought a new solution in better health data
      representation and initial exploration of the Web-based processing of health
      information. CONCLUSION: The designed HERXML has been proven to be an appropriate
      solution in supporting the Web representation of health information. It can be
      used by health practitioners, policy makers, and the public in disease etiology,
      health planning, health resource management, health promotion and health
      education. The utilization of Web-based processing services in this study
      provides a flexible way for users to select and use certain processing functions
      for health data processing and mapping via the Web. This research provides easy
      access to geospatial and health data in understanding the trends of diseases, and
      promotes the growth and enrichment of the CGDI in the public health sector.

PMID- 19159446
TI  - Pseudogene accumulation in the evolutionary histories of Salmonella enterica
      serovars Paratyphi A and Typhi.
AB  - BACKGROUND: Of the > 2000 serovars of Salmonella enterica subspecies I, most
      cause self-limiting gastrointestinal disease in a wide range of mammalian hosts.
      However, S. enterica serovars Typhi and Paratyphi A are restricted to the human
      host and cause the similar systemic diseases typhoid and paratyphoid fever.
      Genome sequence similarity between Paratyphi A and Typhi has been attributed to
      convergent evolution via relatively recent recombination of a quarter of their
      genomes. The accumulation of pseudogenes is a key feature of these and other host
      adapted pathogens, and overlapping pseudogene complements are evident in
      Paratyphi A and Typhi. RESULTS: We report the 4.5 Mbp genome of a clinical
      isolate of Paratyphi A, strain AKU_12601, completely sequenced using capillary
      techniques and subsequently checked using Illumina/Solexa resequencing.
      Comparison with the published genome of Paratyphi A ATCC9150 revealed the two are
      collinear and highly similar, with 188 single nucleotide polymorphisms and 39
      insertions/deletions. A comparative analysis of pseudogene complements of these
      and two finished Typhi genomes (CT18, Ty2) identified several pseudogenes that
      had been overlooked in prior genome annotations of one or both serovars, and
      identified 66 pseudogenes shared between serovars. By determining whether each
      shared and serovar-specific pseudogene had been recombined between Paratyphi A
      and Typhi, we found evidence that most pseudogenes have accumulated after the
      recombination between serovars. We also divided pseudogenes into relative-time
      groups: ancestral pseudogenes inherited from a common ancestor, pseudogenes
      recombined between serovars which likely arose between initial divergence and
      later recombination, serovar-specific pseudogenes arising after recombination but
      prior to the last evolutionary bottlenecks in each population, and more recent
      strain-specific pseudogenes. CONCLUSION: Recombination and pseudogene-formation
      have been important mechanisms of genetic convergence between Paratyphi A and
      Typhi, with most pseudogenes arising independently after extensive recombination
      between the serovars. The recombination events, along with divergence of and
      within each serovar, provide a relative time scale for pseudogene-forming
      mutations, affording rare insights into the progression of functional gene loss
      associated with host adaptation in Salmonella.

PMID- 19159447
TI  - n3 and n6 polyunsaturated fatty acids differentially modulate prostaglandin E
      secretion but not markers of lipogenesis in adipocytes.
AB  - A dramatic rise in the incidence of obesity in the U.S. has accelerated the
      search for interventions that may impact this epidemic. One recently recognized
      target for such intervention is adipose tissue, which secretes a variety of
      bioactive substances including prostaglandins. Prostaglandin E2 (PGE2) has been
      shown to decrease lipolysis in adipocytes, but limited studies have explored
      alternative mechanisms by which PGE2 might impact obesity, such as adipogenesis
      or lipogenesis. Studies conducted on ApcMin/+ mice indicated that selective
      inhibition of the cyclooxygenase (COX)-2 enzyme led to significant reductions in
      fatty acid synthase (FAS) activity in adipose tissue suggesting lipogenic effects
      of PGE2. To further investigate whether these lipid mediators directly regulate
      lipogenesis, we used 3T3-L1 adipocytes to determine the impact of
      eicosapentaenoic acid (EPA) and celecoxib on PGE2 formation and FAS used as a
      lipogenic marker. Both arachidonic acid (AA) and EPA dose-dependently increased
      PGE secretion from adipocytes. AA was expectedly more potent and exhibiting at
      150 uM dose a 5-fold increase in PGE2 secretion over EPA. Despite higher
      secretion of PGE by EPA and AA compared to control, neither PUFA significantly
      altered FAS activity. By contrast both AA and EPA significantly decreased FAS
      mRNA levels. Addition of celecoxib, a selective COX-2 inhibitor, significantly
      decreased PGE2 secretion (p < 0.05) versus control, and also significantly
      decreased FAS activity (p < 0.05). Unexpectedly, the combination of exogenous
      PGE2 and celecoxib further decreased the FAS activity compared to PGE2 alone or
      untreated controls. In conclusion, EPA-mediated inhibition of AA metabolism did
      not significantly alter FAS activity while both AA and EPA significantly
      decreased FAS mRNA expression. COX-2 inhibition significantly decreased PGE2
      production resulting in a decrease in FAS activity and expression that was not
      reversed with the addition of exogenous PGE2, suggesting an additional mechanism
      that is independent of COX-2.

PMID- 19159448
TI  - Atorvastatin ameliorates cerebral vasospasm and early brain injury after
      subarachnoid hemorrhage and inhibits caspase-dependent apoptosis pathway.
AB  - BACKGROUND: Cerebral vasospasm (CVS) and early brain injury remain major causes
      of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH).
      Hydroxymethylglutaryl coenzyme A reductase inhibitors, also known as statins, has
      the neuroprotective effects and ameliorating CVS after SAH. This study was
      designed to explore apoptosis inhibiting effects of atorvastatin and its
      potential apoptotic signal pathway after SAH. RESULTS: Preserving blood-brain
      barrier permeability, decreasing brain edema, increasing neurological scores and
      ameliorating cerebral vasospasm were obtained after prophylactic use of
      atorvastatin. TUNEL-positive cells were reduced markedly both in basilar artery
      and in brain cortex by atorvastatin. Apoptosis-related proteins P53, AIF and
      Cytochrome C were up-regulated after SAH, while they were not affected by
      atorvastatin. In addition, up-regulation of caspase-3 and caspase-8 after SAH was
      decreased by atorvastatin treatment both in mRNA and in protein levels.
      CONCLUSION: The neuroprotective effects of atorvastatin after SAH may be related
      to its inhibition of caspase-dependent proapoptotic pathway based on the present
      results.

PMID- 19159449
TI  - Brugada ECG pattern precipitated by acute pneumonia: a case report.
AB  - Brugada type 1 ECG pattern is the hallmark for the diagnosis of Brugada syndrome
      which is a cause of sudden death due to ventricular arrhythmias. We present a
      case of a previously healthy young man who was admitted with productive cough
      with greenish phlegm and right-sided chest pain which was subsequently diagnosed
      as acute pneumonia. A routine ECG was done as part of his evaluation and showed
      Brugada ECG type 1 pattern. He was treated with antibiotics and on follow up his
      ECG was normal. In this report we present this increasingly described phenomenon
      and briefly review the literature.

PMID- 19159450
TI  - Study of non-Hodgkin's lymphoma mortality associated with industrial pollution in
      Spain, using Poisson models.
AB  - BACKGROUND: Non-Hodgkin's lymphomas (NHLs) have been linked to proximity to
      industrial areas, but evidence regarding the health risk posed by residence near
      pollutant industries is very limited. The European Pollutant Emission Register
      (EPER) is a public register that furnishes valuable information on industries
      that release pollutants to air and water, along with their geographical
      location.This study sought to explore the relationship between NHL mortality in
      small areas in Spain and environmental exposure to pollutant emissions from EPER
      registered industries, using three Poisson-regression-based mathematical models.
      METHODS: Observed cases were drawn from mortality registries in Spain for the
      period 1994-2003. Industries were grouped into the following sectors: energy;
      metal; mineral; organic chemicals; waste; paper; food; and use of solvents.
      Populations having an industry within a radius of 1, 1.5, or 2 kilometres from
      the municipal centroid were deemed to be exposed. Municipalities outside those
      radii were considered as reference populations.The relative risks (RRs)
      associated with proximity to pollutant industries were estimated using the
      following methods: Poisson Regression; mixed Poisson model with random provincial
      effect; and spatial autoregressive modelling (BYM model). RESULTS: Only proximity
      of paper industries to population centres (>2 km) could be associated with a
      greater risk of NHL mortality (mixed model: RR:1.24, 95% CI:1.09-1.42; BYM model:
      RR:1.21, 95% CI:1.01-1.45; Poisson model: RR:1.16, 95% CI:1.06-1.27). Spatial
      models yielded higher estimates. CONCLUSION: The reported association between
      exposure to air pollution from the paper, pulp and board industry and NHL
      mortality is independent of the model used. Inclusion of spatial random effects
      terms in the risk estimate improves the study of associations between
      environmental exposures and mortality.The EPER could be of great utility when
      studying the effects of industrial pollution on the health of the population.

PMID- 19159451
TI  - Identification of novel Bach2 transcripts and protein isoforms through tagging
      analysis of retroviral integrations in B-cell lymphomas.
AB  - BACKGROUND: The Bach2 gene functions as a transcriptional repressor in B-cells,
      showing high expression level only before the plasma cell stage. Several lines of
      evidence indicate that Bach2 is a B-cell specific tumor suppressor. We here
      address patterns of insertional mutagenesis and expression of Bach2 is a murine
      retroviral model of B-cell lymphoma induction. RESULTS: We report that the Bach2
      gene is a target of proviral integrations in B-cell lymphomas induced by murine
      leukemia virus. An alternative Bach2 promoter was identified within intron 2 and
      this promoter was activated in one of the tumors harboring proviral integration.
      The alternative promoter was active in both normal and tumor tissue and the
      tissue specificity of the two Bach2 promoters was similar. Three different
      alternatively used Bach2 terminal exons were identified to be located in intron
      4. The inclusion of these exons resulted in the generation of Bach2 mRNA with
      open reading frames lacking the bZIP DNA binding domain present in the normal
      Bach2 protein, but retaining a partial BTB protein dimerization domain. Such
      Bach2 protein was excluded from the cell nucleus. CONCLUSION: We have identified
      an alternative promoter and new protein isoforms of Bach2. Our data imply that
      activation of an alternative promoter by proviral integration serves as a
      possible mechanism of up-regulation of the Bach2 gene with a potential role in B
      cell lymphomagenesis. The finding of novel Bach2 transcripts and protein isoforms
      will facilitate a better insight into the normal and pathophysiological
      regulation of the Bach2 gene.

PMID- 19159452
TI  - Pore dilation occurs in TRPA1 but not in TRPM8 channels.
AB  - Abundantly expressed in pain-sensing neurons, TRPV1, TRPA1 and TRPM8 are major
      cellular sensors of thermal, chemical and mechanical stimuli. The function of
      these ion channels has been attributed to their selective permeation of small
      cations (e.g., Ca2+, Na+ and K+), and the ion selectivity has been assumed to be
      an invariant fingerprint to a given channel. However, for TRPV1, the notion of
      invariant ion selectivity has been revised recently. When activated, TRPV1
      undergoes time and agonist-dependent pore dilation, allowing permeation of large
      organic cations such as Yo-Pro and NMDG+. The pore dilation is of physiological
      importance, and has been exploited to specifically silence TRPV1-positive sensory
      neurons. It is unknown whether TRPA1 and TRPM8 undergo pore dilation. Here we
      show that TRPA1 activation by reactive or non-reactive agonists induces Yo-Pro
      uptake, which can be blocked by TRPA1 antagonists. In outside-out patch
      recordings using NMDG+ as the sole external cation and Na+ as the internal
      cation, TRPA1 activation results in dynamic changes in permeability to NMDG+. In
      contrast, TRPM8 activation does not produce either Yo-Pro uptake or significant
      change in ion selectivity. Hence, pore dilation occurs in TRPA1, but not in TRPM8
      channels.

PMID- 19159453
TI  - Preventing AVF thrombosis: the rationale and design of the Omega-3 fatty acids
      (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED)
      study.
AB  - BACKGROUND: Haemodialysis (HD) is critically dependent on the availability of
      adequate access to the systemic circulation, ideally via a native arteriovenous
      fistula (AVF). The Primary failure rate of an AVF ranges between 20-54%, due to
      thrombosis or failure of maturation. There remains limited evidence for the use
      of anti-platelet agents and uncertainty as to choice of agent(s) for the
      prevention of AVF thrombosis. We present the study protocol for a randomised,
      double-blind, placebo-controlled, clinical trial examining whether the use of the
      anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in
      combination, will effectively reduce the risk of early thrombosis in de novo AVF.
      METHODS/DESIGN: The study population is adult patients with stage IV or V chronic
      kidney disease (CKD) currently on HD or where HD is planned to start within 6
      months in whom a planned upper or lower arm AVF is to be the primary HD access.
      Using a factorial-design trial, patients will be randomised to aspirin or
      matching placebo, and also to omega-3 fatty acids or matching placebo, resulting
      in four treatment groups (aspirin placebo/omega-3 fatty acid placebo,
      aspirin/omega-3 fatty acid placebo, aspirin placebo/omega-3 fatty acid,
      aspirin/omega-3 fatty acid). Randomisation will be achieved using a dynamic
      balancing method over the two stratification factors of study site and upper
      versus lower arm AVF. The medication will be commenced pre-operatively and
      continued for 3 months post surgery. The primary outcome is patency of the AVF at
      three months after randomisation. Secondary outcome measures will include
      functional patency at six and twelve months, primary patency time, secondary
      (assisted) patency time, and adverse events, particularly bleeding. DISCUSSION:
      This multicentre Australian and New Zealand study has been designed to determine
      whether the outcome of surgery to create de novo AVF can be improved by the use
      of aspirin and/or omega-3 fatty acids. Recently a placebo-controlled trial has
      shown that clopidogrel is effective in safely preventing primary AVF thrombosis,
      but ineffective at increasing functional patency. Our study presents significant
      differences in the anti-platelet agents used, the study design, and surgical and
      patient demographics that should contribute further evidence regarding the
      efficacy of anti-platelet agents. TRIAL REGISTRATION: Australia & New Zealand
      Clinical Trials Register (ACTRN12607000569404).

PMID- 19159454
TI  - Effects of streptozotocin-induced diabetes on the pharmacology of rat conduit and
      resistance intrapulmonary arteries.
AB  - BACKGROUND: Poor control of blood glucose in diabetes is known to promote
      vascular dysfunction and hypertension. Diabetes was recently shown to be linked
      to an increased prevalence of pulmonary hypertension. The aim of this study was
      to determine how the pharmacological reactivity of intrapulmonary arteries is
      altered in a rat model of diabetes. METHODS: Diabetes was induced in rats by the
      beta-cell toxin, streptozotocin (STZ, 60 mg/kg), and isolated conduit and
      resistance intrapulmonary arteries studied 3-4 months later. Isometric tension
      responses to the vasoconstrictors phenylephrine, serotonin and PGF2alpha, and the
      vasodilators carbachol and glyceryl trinitrate, were compared in STZ-treated rats
      and age-matched controls. RESULTS: STZ-induced diabetes significantly blunted the
      maximum response of conduit, but not resistance pulmonary arteries to
      phenylephrine and serotonin, without a change in pEC50. Agonist responses were
      differentially reduced, with serotonin (46% smaller) affected more than
      phenylephrine (32% smaller) and responses to PGF2alpha unaltered.
      Vasoconstriction caused by K+-induced depolarisation remained normal in diabetic
      rats. Endothelium-dependent dilation to carbachol and endothelium-independent
      dilation to glyceryl trinitrate were also unaffected. CONCLUSION: The small
      resistance pulmonary arteries are relatively resistant to STZ-induced diabetes.
      The impaired constrictor responsiveness of conduit vessels was agonist dependent,
      suggesting possible loss of receptor expression or function. The observed effects
      cannot account for pulmonary hypertension in diabetes, rather the impaired
      reactivity to vasoconstrictors would counteract the development of pulmonary
      hypertensive disease.

PMID- 19159455
TI  - Inter-practice variation in diagnosing hypertension and diabetes mellitus: a
      cross-sectional study in general practice.
AB  - BACKGROUND: Previous studies of inter-practice variation of the prevalence of
      hypertension and diabetes mellitus showed wide variations between practices.
      However, in these studies inter-practice variation was calculated without
      controlling for clustering of patients within practices and without adjusting for
      patient and practice characteristics. Therefore, in the present study inter
      practice variation of diagnosed hypertension and diabetes mellitus prevalence
      rates was calculated by 1) using a multi-level design and 2) adjusting for
      patient and practice characteristics. METHODS: Data were used from the
      Netherlands Information Network of General Practice (LINH) in 2004. Of all
      168.045 registered patients, the presence of hypertension, diabetes mellitus and
      all available ICPC coded symptoms and diseases related to hypertension and
      diabetes, were determined. Also, the characteristics of practices were used in
      the analyses. Multilevel logistic regression analyses were performed. RESULTS:
      The 95% prevalence range for the practices for the prevalence of diagnosed
      hypertension and diabetes mellitus was 66.3 to 181.7 per 1000 patients and 22.2
      to 65.8 per 1000 patients, respectively, after adjustment for patient and
      practice characteristics. The presence of hypertension and diabetes was best
      predicted by patient characteristics. The most important predictors of
      hypertension were obesity (OR = 3.5), presence of a lipid disorder (OR = 3.0),
      and diabetes mellitus (OR = 2.6), whereas the presence of diabetes mellitus was
      particularly predicted by retinopathy (OR = 8.5), lipid disorders (OR = 2.8) and
      hypertension (OR = 2.7). CONCLUSION: Although not the optimal case-mix could be
      used in this study, we conclude that even after adjustment for patient
      (demographic variables and risk factors for hypertension and diabetes mellitus)
      and practice characteristics (practice size and presence of a practice nurse),
      there is a wide difference between general practices in the prevalence rates of
      diagnosed hypertension and diabetes mellitus.

PMID- 19159456
TI  - Associations between lamb survival and prion protein genotype: analysis of data
      for ten sheep breeds in Great Britain.
AB  - BACKGROUND: Selective breeding programmes, based on prion protein (PrP) genotype,
      have been introduced throughout the European Union to reduce the risk of sheep
      transmissible spongiform encephalopathies (TSEs). These programmes could have
      negative consequences on other important traits, such as fitness and production
      traits, if the PrP gene has pleiotropic effects or is in linkage disequilibrium
      with genes affecting these traits. This paper presents the results of an
      investigation into associations between lamb survival and PrP genotype in ten
      mainstream sheep breeds in Great Britain (GB). In addition, the reasons for lamb
      deaths were examined in order to identify any associations between these and PrP
      genotype. RESULTS: Survival times from birth to weaning were analysed for over
      38000 lambs (2427 dead and 36096 live lambs) from 128 flocks using Cox
      proportional hazard models for each breed, including additive animal genetic
      effects. No significant associations between PrP genotype and lamb survival were
      identified, except in the Charollais breed for which there was a higher risk of
      mortality in lambs of the ARR/VRQ genotype compared with those of the ARR/ARR
      genotype. Significant effects of birth weight, litter size, sex, age of dam and
      year of birth on survival were also identified. For all breeds the reasons for
      death changed significantly with age; however, no significant associations
      between reason for death and PrP genotype were found for any of the breeds.
      CONCLUSION: This study found no evidence to suggest that a selective breeding
      programme based on PrP genotype will have a detrimental effect on lamb survival.
      The only significant effect of PrP genotype identified was likely to be of little
      consequence because an increased risk of mortality was associated with a genotype
      that is selected against in current breeding strategies.

PMID- 19159457
TI  - Efficient yeast ChIP-Seq using multiplex short-read DNA sequencing.
AB  - BACKGROUND: Short-read high-throughput DNA sequencing technologies provide new
      tools to answer biological questions. However, high cost and low throughput limit
      their widespread use, particularly in organisms with smaller genomes such as S.
      cerevisiae. Although ChIP-Seq in mammalian cell lines is replacing array-based
      ChIP-chip as the standard for transcription factor binding studies, ChIP-Seq in
      yeast is still underutilized compared to ChIP-chip. We developed a multiplex
      barcoding system that allows simultaneous sequencing and analysis of multiple
      samples using Illumina's platform. We applied this method to analyze the
      chromosomal distributions of three yeast DNA binding proteins (Ste12, Cse4 and
      RNA PolII) and a reference sample (input DNA) in a single experiment and
      demonstrate its utility for rapid and accurate results at reduced costs. RESULTS:
      We developed a barcoding ChIP-Seq method for the concurrent analysis of
      transcription factor binding sites in yeast. Our multiplex strategy generated
      high quality data that was indistinguishable from data obtained with non-barcoded
      libraries. None of the barcoded adapters induced differences relative to a non
      barcoded adapter when applied to the same DNA sample. We used this method to map
      the binding sites for Cse4, Ste12 and Pol II throughout the yeast genome and we
      found 148 binding targets for Cse4, 823 targets for Ste12 and 2508 targets for
      PolII. Cse4 was strongly bound to all yeast centromeres as expected and the
      remaining non-centromeric targets correspond to highly expressed genes in rich
      media. The presence of Cse4 non-centromeric binding sites was not reported
      previously. CONCLUSION: We designed a multiplex short-read DNA sequencing method
      to perform efficient ChIP-Seq in yeast and other small genome model organisms.
      This method produces accurate results with higher throughput and reduced cost.
      Given constant improvements in high-throughput sequencing technologies,
      increasing multiplexing will be possible to further decrease costs per sample and
      to accelerate the completion of large consortium projects such as modENCODE.

PMID- 19159458
TI  - Barriers to implementation of a computerized decision support system for
      depression: an observational report on lessons learned in "real world" clinical
      settings.
AB  - BACKGROUND: Despite wide promotion, clinical practice guidelines have had limited
      effect in changing physician behavior. Effective implementation strategies to
      date have included: multifaceted interventions involving audit and feedback,
      local consensus processes, marketing; reminder systems, either manual or
      computerized; and interactive educational meetings. In addition, there is now
      growing evidence that contextual factors affecting implementation must be
      addressed such as organizational support (leadership procedures and resources)
      for the change and strategies to implement and maintain new systems. METHODS: To
      examine the feasibility and effectiveness of implementation of a computerized
      decision support system for depression (CDSS-D) in routine public mental health
      care in Texas, fifteen study clinicians (thirteen physicians and two advanced
      nurse practitioners) participated across five sites, accruing over 300 outpatient
      visits on 168 patients. RESULTS: Issues regarding computer literacy and
      hardware/software requirements were identified as initial barriers. Clinicians
      also reported concerns about negative impact on workflow and the potential need
      for duplication during the transition from paper to electronic systems of medical
      record keeping. CONCLUSION: The following narrative report based on observations
      obtained during the initial testing and use of a CDSS-D in clinical settings
      further emphasizes the importance of taking into account organizational factors
      when planning implementation of evidence-based guidelines or decision support
      within a system.

PMID- 19159459
TI  - Identification of two proteins that interact with the Erp virulence factor from
      Mycobacterium tuberculosis by using the bacterial two-hybrid system.
AB  - BACKGROUND: The exported repetitive protein (erp) gene encodes a secreted 36-kDa
      protein with a central domain containing several proline-glycine-leucine
      threonine-serine (PGLTS) repeats. It has been demonstrated that erp is a
      virulence-associated factor since the disruption of this gene impairs the growth
      of Mycobacterium bovis and Mycobacterium tuberculosis in mice. RESULTS: In order
      to elucidate the function of Erp we searched for Erp-binding proteins from M.
      tuberculosis by using a bacterial two-hybrid system. Our results indicate that
      Erp interacts specifically with two putative membrane proteins, Rv1417 and
      Rv2617c. Further analysis revealed that the latter two interact with each other,
      indicating that Rv1417, Rv2617c and Erp are connected through multiple
      interactions. While Rv1417 is disseminated in several Actinomycetales genera,
      orthologues of Rv2617c are exclusively present in members of the M. tuberculosis
      complex (MTC). The central and amino-terminal regions of Erp were determined to
      be involved in the interaction with Rv1417 and Rv2627c. Erp forms from
      Mycobacterium smegmatis and Mycobacterium leprae were not able to interact with
      Rv2617c in two-hybrid assays. Immunolocalization experiments showed that Rv1417
      and Rv2617c are found on the cell membrane and Erp on the bacterial cell wall.
      Finally, comparative genomics and expression studies revealed a possible role of
      Rv1417 in riboflavin metabolism. CONCLUSION: We identified interactive partners
      of Erp, an M. tuberculosis protein involved in virulence, which will be the focus
      of future investigation to decipher the function of the Erp family protein.

PMID- 19159460
TI  - Biomedical word sense disambiguation with ontologies and metadata: automation
      meets accuracy.
AB  - BACKGROUND: Ontology term labels can be ambiguous and have multiple senses. While
      this is no problem for human annotators, it is a challenge to automated methods,
      which identify ontology terms in text. Classical approaches to word sense
      disambiguation use co-occurring words or terms. However, most treat ontologies as
      simple terminologies, without making use of the ontology structure or the
      semantic similarity between terms. Another useful source of information for
      disambiguation are metadata. Here, we systematically compare three approaches to
      word sense disambiguation, which use ontologies and metadata, respectively.
      RESULTS: The 'Closest Sense' method assumes that the ontology defines multiple
      senses of the term. It computes the shortest path of co-occurring terms in the
      document to one of these senses. The 'Term Cooc' method defines a log-odds ratio
      for co-occurring terms including co-occurrences inferred from the ontology
      structure. The 'MetaData' approach trains a classifier on metadata. It does not
      require any ontology, but requires training data, which the other methods do not.
      To evaluate these approaches we defined a manually curated training corpus of
      2600 documents for seven ambiguous terms from the Gene Ontology and MeSH. All
      approaches over all conditions achieve 80% success rate on average. The
      'MetaData' approach performed best with 96%, when trained on high-quality data.
      Its performance deteriorates as quality of the training data decreases. The 'Term
      Cooc' approach performs better on Gene Ontology (92% success) than on MeSH (73%
      success) as MeSH is not a strict is-a/part-of, but rather a loose is-related-to
      hierarchy. The 'Closest Sense' approach achieves on average 80% success rate.
      CONCLUSION: Metadata is valuable for disambiguation, but requires high quality
      training data. Closest Sense requires no training, but a large, consistently
      modelled ontology, which are two opposing conditions. Term Cooc achieves greater
      90% success given a consistently modelled ontology. Overall, the results show
      that well structured ontologies can play a very important role to improve
      disambiguation. AVAILABILITY: The three benchmark datasets created for the
      purpose of disambiguation are available in Additional file 1.

PMID- 19159461
TI  - Conserved retinoblastoma protein-binding motif in human cytomegalovirus UL97
      kinase minimally impacts viral replication but affects susceptibility to
      maribavir.
AB  - The UL97 kinase has been shown to phosphorylate and inactivate the retinoblastoma
      protein (Rb) and has three consensus Rb-binding motifs that might contribute to
      this activity. Recombinant viruses containing mutations in the Rb-binding motifs
      generally replicated well in human foreskin fibroblasts with only a slight delay
      in replication kinetics. Their susceptibility to the specific UL97 kinase
      inhibitor, maribavir, was also examined. Mutation of the amino terminal motif,
      which is involved in the inactivation of Rb, also renders the virus
      hypersensitive to the drug and suggests that the motif may play a role in its
      mechanism of action.

PMID- 19159462
TI  - A novel Ecotin-Ubiquitin-Tag (ECUT) for efficient, soluble peptide production in
      the periplasm of Escherichia coli.
AB  - BACKGROUND: Many protocols for recombinant production of peptides and proteins
      include secretion into the periplasmic space of Escherichia coli, as they may not
      properly fold in the cytoplasm. If a signal peptide is not sufficient for
      translocation, a larger secretion moiety can instead be fused to the gene of
      interest. However, due to the covalent linkage of the proteins, a protease
      recognition site needs to be introduced in between, altering the N-terminus of
      the product. In the current study, we combined the ubiquitin fusion technology,
      which allows production of authentic peptides and proteins, with secretion by the
      perpiplasmic protease inhibitor ecotin. RESULTS: Different fusion constructs,
      composed of ecotin, mouse ubiquitin b and a model peptide, were expressed in E.
      coli BL21(DE3). The fusion proteins were translocated into the periplasmic space
      and the ecotin signal peptide was cleaved off. Under the control of the lacUV5
      promoter at 24 degrees C we obtained 18 mg periplasmic recombinant protein per
      gram dry cell weight. However, vigorous expression with the T7 promoter caused
      outer membrane permeabilization and leakage of the fusion protein into the
      culture medium. Target peptides were released from hybrid proteins by the
      deubiquitinating enzyme ubiquitin c-terminal hydrolase-L3 in vitro. MALDI TOF-TOF
      mass spectroscopy confirmed accurate cleavage. CONCLUSION: This newly described
      method represents a useful technique for the production of authentic soluble
      peptides in the periplasm of E. coli. In addition, larger proteins might also be
      produced with the current system by the use of ubiquitin specific proteases,
      which can cleave off larger C-terminal extensions.

PMID- 19159463
TI  - Giant cell tumor of talus: a case report.
AB  - Giant cell tumor of talus is a rare entity. In contrast to GCT of long bones,
      most cases occur in a younger age group and tend to be multicentric. The authors
      report a case of GCT in a 19 year old boy which had led to extensive destruction
      of the talus. In view of the extensive involvement, total talectomy along with
      tibio - calcaneal arthrodesis was performed. At 6 months of followup, the patient
      had a painless and well arthrodesed ankle. There was no evidence of recurrence at
      18 months of followup.

PMID- 19159464
TI  - EPIC-DB: a proteomics database for studying Apicomplexan organisms.
AB  - BACKGROUND: High throughput proteomics experiments are useful for analyzing the
      protein expression of an organism, identifying the correct gene structure of a
      genome, or locating possible post-translational modifications within proteins.
      High throughput methods necessitate publicly accessible and easily queried
      databases for efficiently and logically storing, displaying, and analyzing the
      large volume of data. DESCRIPTION: EPICDB is a publicly accessible, queryable,
      relational database that organizes and displays experimental, high throughput
      proteomics data for Toxoplasma gondii and Cryptosporidium parvum. Along with
      detailed information on mass spectrometry experiments, the database also provides
      antibody experimental results and analysis of functional annotations, comparative
      genomics, and aligned expressed sequence tag (EST) and genomic open reading frame
      (ORF) sequences. The database contains all available alternative gene datasets
      for each organism, which comprises a complete theoretical proteome for the
      respective organism, and all data is referenced to these sequences. The database
      is structured around clusters of protein sequences, which allows for the
      evaluation of redundancy, protein prediction discrepancies, and possible splice
      variants. The database can be expanded to include genomes of other organisms for
      which proteome-wide experimental data are available. CONCLUSION: EPICDB is a
      comprehensive database of genome-wide T. gondii and C. parvum proteomics data and
      incorporates many features that allow for the analysis of the entire proteomes
      and/or annotation of specific protein sequences. EPICDB is complementary to other
      -genomics- databases of these organisms by offering complete mass spectrometry
      analysis on a comprehensive set of all available protein sequences.

PMID- 19159465
TI  - New DArT markers for oat provide enhanced map coverage and global germplasm
      characterization.
AB  - BACKGROUND: Genomic discovery in oat and its application to oat improvement have
      been hindered by a lack of genetic markers common to different genetic maps, and
      by the difficulty of conducting whole-genome analysis using high-throughput
      markers. This study was intended to develop, characterize, and apply a large set
      of oat genetic markers based on Diversity Array Technology (DArT). RESULTS:
      Approximately 19,000 genomic clones were isolated from complexity-reduced genomic
      representations of pooled DNA samples from 60 oat varieties of global origin.
      These were screened on three discovery arrays, with more than 2000 polymorphic
      markers being identified for use in this study, and approximately 2700
      potentially polymorphic markers being identified for use in future studies. DNA
      sequence was obtained for 2573 clones and assembled into a non-redundant set of
      1770 contigs and singletons. Of these, 705 showed highly significant (Expectation
      < 10E-10) BLAST similarity to gene sequences in public databases. Based on marker
      scores in 80 recombinant inbred lines, 1010 new DArT markers were used to
      saturate and improve the 'Kanota' x 'Ogle' genetic map. DArT markers provided map
      coverage approximately equivalent to existing markers. After binning markers from
      similar clones, as well as those with 99% scoring similarity, a set of 1295 non
      redundant markers was used to analyze genetic diversity in 182 accessions of
      cultivated oat of worldwide origin. Results of this analysis confirmed that major
      clusters of oat diversity are related to spring vs. winter type, and to the
      presence of major breeding programs within geographical regions. Secondary
      clusters revealed groups that were often related to known pedigree structure.
      CONCLUSION: These markers will provide a solid basis for future efforts in
      genomic discovery, comparative mapping, and the generation of an oat consensus
      map. They will also provide new opportunities for directed breeding of superior
      oat varieties, and guidance in the maintenance of oat genetic diversity.

PMID- 19159466
TI  - The human Ago2 MC region does not contain an eIF4E-like mRNA cap binding motif.
AB  - BACKGROUND: Argonaute (Ago) proteins interact with small regulatory RNAs to
      mediate gene regulatory pathways. A recent report by Kiriakidou et al. 1
      describes an MC sequence region identified in Ago2 that displays similarity to
      the cap-binding motif in translation initiation factor 4E (eIF4E). In a cap-bound
      eIF4E structure, two important aromatic residues of the motif stack on either
      side of a 7-methylguanosine 5'-triphosphate (m7Gppp) base. The corresponding Ago2
      aromatic residues (F450 and F505) were hypothesized to perform the same cap
      binding function. However, the detected similarity between the MC sequence and
      the eIF4E cap-binding motif was questionable. RESULTS: A number of sequence-based
      and structure-based bioinformatics methods reveal the reported similarity between
      the Ago2 MC sequence region and the eIF4E cap-binding motif to be spurious.
      Alternatively, the MC sequence region is confidently assigned to the N-terminus
      of the Ago piwi module, within the mid domain of experimentally determined
      prokaryotic Ago structures. Confident mapping of the Ago2 MC sequence region to
      the piwi mid domain results in a homology-based structure model that positions
      the identified aromatic residues over 20 A apart, with one of the aromatic side
      chains (F450) contributing instead to the hydrophobic core of the domain.
      CONCLUSION: Correct functional prediction based on weak sequence similarity
      requires substantial evolutionary and structural support. The evolutionary
      context of the Ago mid domain suggested by multiple sequence alignment is limited
      to a conserved hydrophobicity profile required for the fold and a motif following
      the MC region that binds guide RNA. Mapping of the MC sequence to the mid domain
      structure reveals Ago2 aromatics that are incompatible with eIF4E-like mRNA cap
      binding, yet display some limited local structure similarities that cause the
      chance sequence match to eIF4E.

PMID- 19159467
TI  - Recent advances of novel targeted therapy in non-small cell lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths world-wide. Recent advances in
      cancer biology have led to the identification of new targets in neoplastic cells
      and the development of novel targeted therapies. At this time, two targeted
      agents are approved by the FDA in advanced non-small cell lung cancer (NSCLC):
      the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)
      erlotinib, and the anitangiogenic bevacizumab. A third agent, cetuximab, which
      was recently shown to enhance survival when used with cisplatin and vinorelbine
      as first line therapy for advanced NSCLC, will likely be approved by regulatory
      agencies. With more than 500 molecularly targeted agents under development, the
      prospects of identifying novel therapies that benefit individual patients with
      lung cancer are bright.

PMID- 19159468
TI  - Use of ecstasy and other psychoactive substances among school-attending
      adolescents in Taiwan: national surveys 2004-2006.
AB  - BACKGROUND: With the backdrop of a global ecstasy epidemic, this study sought to
      examine the trend, correlates, and onset sequence of ecstasy use among
      adolescents in Taiwan, where a well-established gateway drug such as marijuana is
      much less popular. METHODS: A multistage probability survey of school-attending
      adolescents in grades 7, 9, 10, and 12, aged 11-19 years, was conducted in 2004,
      2005, and 2006. A self-administered anonymous questionnaire elicited response
      rates ranging from 94.3% to 96.6%. The sample sizes were 18232 respondents in
      2004, 17986 in 2005, and 17864 in 2006. RESULTS: In terms of lifetime prevalence
      and incidence, ecstasy and ketamine by and large appeared as the first and second
      commonly used illegal drugs, respectively, among middle (grades 7 and 9) and high
      school students (grades 10 and 12) during the 3-year survey period; however, this
      order was reversed in the middle school-aged students starting in 2006. Having
      sexual experience, tobacco use, and betel nut use were factors consistently
      associated with the onset of ecstasy use across years. The majority of ecstasy
      users had been involved in polydrug use, such as the use of ketamine (41.4%
      53.5%), marijuana (12.7%-18.7%), and methamphetamine (4.2%-9.5%). CONCLUSION:
      From 2004 to 2006, a decline was noted in the prevalence and incidence rate of
      ecstasy, a leading illegal drug used by school-attending adolescents in Taiwan
      since the early 2000s. The emerging ketamine use trend may warrant more attention
      in the future.

PMID- 19159469
TI  - Childhood habit cough treated with consultation by telephone: a case report.
AB  - BACKGROUND: Childhood habit cough has been treated successfully by making
      suggestions that it can be stopped, desensitization techniques, use of
      distractors, provision of rewards, and self-hypnosis. All of these techniques
      have involved personal contact between a health care provider and a patient. CASE
      PRESENTATION: A 5-year-old with cystic fibrosis was diagnosed with habit cough
      following evaluation by a pediatric pulmonologist and otolaryngologist. An expert
      in the treatment of habit cough provided instruction by telephone to the
      patient's mother regarding use of hypnotic techniques in this setting, which was
      associated with resolution of the cough within a week. CONCLUSION: As this report
      describes a single patient, it is possible that his improvement was unrelated to
      the given advice. Therefore, it remains to be seen whether therapy by telephone
      for habit cough is applicable widely.

PMID- 19159470
TI  - Non-prostatic pathology on prostate needle-biopsy - colorectal carcinoid: a case
      report.
AB  - INTRODUCTION: Prostate needle-biopsies are among the most common specimens in
      routine histopathological practice; in 15% colorectal tissue is also present.
      Rectal pathology is described to be found in 17% of this coincidentally obtained
      material. CASE PRESENTATION: We present a case in which colorectal carcinoid was
      found in the rectal mucosa obtained via transrectal prostate biopsies in a
      screening program for prostate cancer in a 71-year old Caucasian male. To the
      best of our knowledge, this was the first time that such a coincidental finding
      was discovered. Besides a colonoscopy with polypectomy, this coincidental
      detection remained without any further clinical consequences for this patient
      until today. CONCLUSION: As there is a considerable chance that abnormalities are
      found in the rectal tissue of prostate biopsies, it is advisable for all
      pathologists to include this tissue in the histology evaluation and look for
      potential irregularities in this simultaneously collected material.

PMID- 19159471
TI  - Impact of collimator leaf width and treatment technique on stereotactic
      radiosurgery and radiotherapy plans for intra- and extracranial lesions.
AB  - BACKGROUND: This study evaluated the dosimetric impact of various treatment
      techniques as well as collimator leaf width (2.5 vs 5 mm) for three groups of
      tumors -- spine tumors, brain tumors abutting the brainstem, and liver tumors.
      These lesions often present challenges in maximizing dose to target volumes
      without exceeding critical organ tolerance. Specifically, this study evaluated
      the dosimetric benefits of various techniques and collimator leaf sizes as a
      function of lesion size and shape. METHODS: Fifteen cases (5 for each site) were
      studied retrospectively. All lesions either abutted or were an integral part of
      critical structures (brainstem, liver or spinal cord). For brain and liver
      lesions, treatment plans using a 3D-conformal static technique (3D), dynamic
      conformal arcs (DARC) or intensity modulation (IMRT) were designed with a
      conventional linear accelerator with standard 5 mm leaf width multi-leaf
      collimator, and a linear accelerator dedicated for radiosurgery and
      hypofractionated therapy with a 2.5 mm leaf width collimator. For the concave
      spine lesions, intensity modulation was required to provide adequate
      conformality; hence, only IMRT plans were evaluated using either the standard or
      small leaf-width collimators.A total of 70 treatment plans were generated and
      each plan was individually optimized according to the technique employed. The
      Generalized Estimating Equation (GEE) was used to separate the impact of
      treatment technique from the MLC system on plan outcome, and t-tests were
      performed to evaluate statistical differences in target coverage and organ
      sparing between plans. RESULTS: The lesions ranged in size from 2.6 to 12.5 cc,
      17.5 to 153 cc, and 20.9 to 87.7 cc for the brain, liver, and spine groups,
      respectively. As a group, brain lesions were smaller than spine and liver
      lesions. While brain and liver lesions were primarily ellipsoidal, spine lesions
      were more complex in shape, as they were all concave. Therefore, the brain and
      the liver groups were compared for volume effect, and the liver and spine groups
      were compared for shape. For the brain and liver groups, both the radiosurgery
      MLC and the IMRT technique contributed to the dose sparing of organs-at
      risk(OARs), as dose in the high-dose regions of these OARs was reduced up to 15%,
      compared to the non-IMRT techniques employing a 5 mm leaf-width collimator. Also,
      the dose reduction contributed by the fine leaf-width MLC decreased, as dose
      savings at all levels diminished from 4 - 11% for the brain group to 1 - 5% for
      the liver group, as the target structures decreased in volume. The fine leaf
      width collimator significantly improved spinal cord sparing, with dose reductions
      of 14 - 19% in high to middle dose regions, compared to the 5 mm leaf width
      collimator. CONCLUSION: The fine leaf-width MLC in combination with the IMRT
      technique can yield dosimetric benefits in radiosurgery and hypofractionated
      radiotherapy. Treatment of small lesions in cases involving complex target/OAR
      geometry will especially benefit from use of a fine leaf-width MLC and the use of
      IMRT.

PMID- 19159472
TI  - Publication trends in the medical informatics literature: 20 years of "Medical
      Informatics" in MeSH.
AB  - BACKGROUND: The purpose of this study is to identify publication output, and
      research areas, as well as descriptively and quantitatively characterize the
      field of medical informatics through publication trend analysis over a twenty
      year period (1987-2006). METHODS: A bibliometric analysis of medical informatics
      citations indexed in Medline was performed using publication trends, journal
      frequency, impact factors, MeSH term frequencies and characteristics of
      citations. RESULTS: There were 77,023 medical informatics articles published
      during this 20 year period in 4,644 unique journals. The average annual article
      publication growth rate was 12%. The 50 identified medical informatics MeSH terms
      are rarely assigned together to the same document and are almost exclusively
      paired with a non-medical informatics MeSH term, suggesting a strong
      interdisciplinary trend. Trends in citations, journals, and MeSH categories of
      medical informatics output for the 20-year period are summarized. Average impact
      factor scores and weighted average impact factor scores increased over the 20
      year period with two notable growth periods. CONCLUSION: There is a steadily
      growing presence and increasing visibility of medical informatics literature over
      the years. Patterns in research output that seem to characterize the historic
      trends and current components of the field of medical informatics suggest it may
      be a maturing discipline, and highlight specific journals in which the medical
      informatics literature appears most frequently, including general medical
      journals as well as informatics-specific journals.

PMID- 19159473
TI  - Do implementation issues influence the effectiveness of medications? The case of
      nicotine replacement therapy and bupropion in UK Stop Smoking Services.
AB  - BACKGROUND: Effective pharmacotherapies are available for smoking cessation but
      their efficacy is established through randomised controlled trials where the
      medication is supplied direct to subjects. In health care settings patient access
      to medicines is often less direct. The process for obtaining supplies of nicotine
      replacement therapy (NRT) is relatively easy for smokers attending National
      Health Service (NHS) Stop Smoking Services in the UK, whilst this is not
      necessarily the case for those wishing to using prescription only medicines (e.g.
      bupropion and varenicline). This study was a direct comparison of the short-term
      validated abstinence rates of NRT and bupropion in a clinical setting. METHODS:
      Data were routinely collected from 2626 clients setting a quit date (82% of those
      registering) with two London NHS Stop Smoking Services that offered behavioural
      support combined with pharmacotherapy (NRT and bupropion). RESULTS: Contrary to
      what would be expected from multiple randomised controlled trials, the CO
      validated 3-4 week abstinence rate in clients using NRT was higher than for
      bupropion (42% versus 34%, p = .003). This difference persisted even when
      controlling for smoking characteristics, demographic variables and treatment
      variables 1.40 (95% CI = 1.08 - 1.83). CONCLUSION: Given that the level of
      behavioural support received by clients on each medication was identical, the
      most plausible explanation for the difference in effectiveness between NRT and
      bupropion perhaps lies with how clients of the Stop Smoking Services obtained
      their medications. Obtaining NRT was relatively easy for clients throughout the
      study period whilst this was not the case for bupropion. This study suggests that
      implementation issues and/or self-selection may influence the effectiveness of
      medications in health care, as opposed to research, settings.

PMID- 19159474
TI  - Measuring agreement of administrative data with chart data using prevalence
      unadjusted and adjusted kappa.
AB  - BACKGROUND: Kappa is commonly used when assessing the agreement of conditions
      with reference standard, but has been criticized for being highly dependent on
      the prevalence. To overcome this limitation, a prevalence-adjusted and bias
      adjusted kappa (PABAK) has been developed. The purpose of this study is to
      demonstrate the performance of Kappa and PABAK, and assess the agreement between
      hospital discharge administrative data and chart review data conditions. METHODS:
      The agreement was compared for random sampling, restricted sampling by
      conditions, and case-control sampling from the four teaching hospitals in
      Alberta, Canada from ICD10 administrative data during January 1, 2003 and June
      30, 2003. A total of 4,008 hospital discharge records and chart view, linked for
      personal unique identifier and admission date, for 32 conditions of random
      sampling were analyzed. The restricted sample for hypertension, myocardial
      infarction and congestive heart failure, and case-control sample for those three
      conditions were extracted from random sample. The prevalence, kappa, PABAK,
      positive agreement, negative agreement for the condition was compared for each of
      three samples. RESULTS: The prevalence of each condition was highly dependent on
      the sampling method, and this variation in prevalence had a significant effect on
      both kappa and PABAK. PABAK values were obviously high for certain conditions
      with low kappa values. The gap between these two statistical values for the same
      condition narrowed as the prevalence of the condition approached 50%. CONCLUSION:
      Kappa values varied more widely than PABAK values across the 32 conditions. PABAK
      values should usually not be interpreted as measuring the same agreement as kappa
      in administrative data, particular for the condition with low prevalence. There
      is no single statistic measuring agreement that captures the desired information
      for validity of administrative data. Researchers should report kappa, the
      prevalence, positive agreement, negative agreement, and the relative frequency in
      each cell (i.e. a, b, c and d) to enable the reader to judge the validity of
      administrative data from multiple aspects.

PMID- 19159475
TI  - NAOMI: The trials and tribulations of implementing a heroin assisted treatment
      study in North America.
AB  - BACKGROUND: Opioid addiction is a chronic, relapsing disease and remains a major
      public health challenge. Despite important expansions of access to conventional
      treatments, there are still significant proportions of affected individuals who
      remain outside the reach of the current treatment system and who contribute
      disproportionately to health care and criminal justice costs as well as to public
      disorder associated with drug addiction.The NAOMI study is a Phase III randomized
      clinical trial comparing injectable heroin maintenance to oral methadone. The
      study has ethics board approval at its Montreal and Vancouver sites, as well as
      from the University of Toronto, the New York Academy of Medicine and Johns
      Hopkins University.The main objective of the NAOMI Study is to determine whether
      the closely supervised provision of injectable, pharmaceutical-grade opioid
      agonist is more effective than methadone alone in recruiting, retaining, and
      benefiting chronic, opioid-dependent, injection drug users who are resistant to
      current standard treatment options. METHODS: The case study submitted chronicles
      the challenges of getting a heroin assisted treatment trial up and running in
      North America. It describes: a brief background on opioid addiction; current
      standard therapies for opioid addiction; why there is/was a need for a heroin
      assisted treatment trial; a description of heroin assisted treatment; the
      beginnings of creating the NAOMI study in North America; what is the NAOMI study;
      the science and politics of the NAOMI study; getting NAOMI started in Canada;
      various requirements and restrictions in getting the study up and running;
      recruitment into the study; working with the media; a status report on the study;
      and a brief conclusion from the authors' perspectives. RESULTS AND CONCLUSION: As
      this is a case study, there are no specific results or main findings listed. The
      case study focuses on: the background of the study; what it took to get the study
      started in Canada; the unique requirements and conditions of getting a site, and
      the study, approved; working with the media; recruitment into the study; a brief
      status report on the study; and a brief conclusion from the authors'
      perspectives. TRIAL REGISTRATION: ClinicalTrials.gov registration number:
      NCT00175357.

PMID- 19159476
TI  - Steps in the design, development and formative evaluation of obesity prevention
      related behavior change trials.
AB  - Obesity prevention interventions through dietary and physical activity change
      have generally not been effective. Limitations on possible program effectiveness
      are herein identified at every step in the mediating variable model, a generic
      conceptual framework for understanding how interventions may promote behavior
      change. To minimize these problems, and thereby enhance likely intervention
      effectiveness, four sequential types of formative studies are proposed: targeted
      behavior validation, targeted mediator validation, intervention procedure
      validation, and pilot feasibility intervention. Implementing these studies would
      establish the relationships at each step in the mediating variable model, thereby
      maximizing the likelihood that an intervention would work and its effects would
      be detected. Building consensus among researchers, funding agencies, and journal
      editors on distinct intervention development studies should avoid identified
      limitations and move the field forward.

PMID- 19159477
TI  - An emergency clinical pathway for stroke patients--results of a cluster
      randomised trial (isrctn41456865).
AB  - BACKGROUND: Emergency Clinical Pathways (ECP) for stroke have never been tested
      in randomized controlled trials (RCTs). OBJECTIVE: To evaluate the effectiveness
      of an ECP for stroke patients in Latium (Italy) emergency system. METHODS:
      cluster-RCT designed to compare stroke patient referrals by Emergency Medical
      Service (EMS) and Emergency Room (ER) health professionals trained in the ECP,
      with those of non-trained EMS and ER controls. Primary outcome measure was the
      proportion of eligible (aged </= 80 and symptom onset </= 6 hours) stroke
      patients referred to a stroke unit (SU). Intention to treat (ITT) and per
      protocol (PP) analyses were performed, and risk ratios (RR) adjusted by age,
      gender and area, were calculated. RESULTS: 2656 patients in the intervention arm
      and 2239 in the control arm required assistance; 78.3% of the former and 80.6% of
      the latter were admitted to hospitals, and respectively 74.8% and 78.3% were
      confirmed strokes. Of the eligible confirmed strokes, 106/434 (24.4%) in the
      intervention arm and 43/328 (13.1%) in the control arm were referred to the SU in
      the ITT analysis (RR = 2.01; 95% CI: 0.79-4.00), and respectively 105/243 (43.2%)
      and 43/311 (13.8%) in the PP analysis (RR = 3.21; 95%CI: 1.62-4.98). Of patients
      suitable for i.v. thrombolysis, 15/175 (8.6%) in the intervention arm and 2/115
      (1.7%) in the control arm received thrombolysis (p = 0.02) in the ITT analysis,
      and respectively 15/99 (15.1%) and 2/107 (1.9%)(p = 0.001) in the PP analysis.
      CONCLUSION: Our data suggest potenti efficiency and feasibility of an ECP. The
      integration of EMS and ERs with SU networks for organised acute stroke care is
      feasible and may ameliorate the quality of care for stroke patients. TRIAL
      REGISTRATION: Current Controlled Trials (ISRCTN41456865).

PMID- 19159478
TI  - Disclosure of symptoms of postnatal depression, the perspectives of health
      professionals and women: a qualitative study.
AB  - BACKGROUND: In the UK, 8-15% of women suffer from postnatal depression with long
      term consequences for maternal mood and child development. Current guidelines
      state that health visitors and GPs should continue to have a major role in the
      detection and management of postnatal depression. Previous literature suggests
      that women are reluctant to disclose symptoms of postnatal depression. This study
      aimed to explore general practitioners' (GPs), health visitors' and women's views
      on the disclosure of symptoms which may indicate postnatal depression in primary
      care. METHODS: In-depth interviews with GPs, health visitors and women who were
      participating in a randomised controlled trial of anti-depressants versus health
      visitor delivered non-directive counselling for the treatment of postnatal
      depression. Interviews were audio-taped and fully transcribed. Thematic analysis
      with an iterative approach was used, allowing the views of practitioners and
      patients to be explored and then compared. RESULTS: Nineteen GPs, 14 health
      visitors and 28 women were interviewed. A number of common themes were identified
      across all three data sets: understanding and negotiating the diagnosis of
      postnatal depression, hindering and facilitating disclosure, and the system of
      care. Both women and health professionals described postnatal depression in
      psychosocial terms: an adjustment reaction to change in life circumstances and
      the reality of motherhood not meeting personal expectations. Women described
      making a conscious decision about whether or not to disclose their feelings to
      their GP or health visitor. Health professionals described strategies used to
      hinder disclosure and described a reluctance to make a diagnosis of postnatal
      depression, as they had few personal resources to manage women with postnatal
      depression themselves, and no services to which to refer women for further
      treatment. CONCLUSION: To improve disclosure of symptoms in primary care, there
      should be a move away from questioning why health professionals do not make the
      diagnosis of depression and in response suggesting that education and training
      will improve skills and thus improve detection of depression. Improving the
      detection and management of postnatal depression in primary care requires
      recognition of the context in which women consult, and system changes that ensure
      health professionals work in an environment that can facilitate disclosure and
      that the necessary resources for management are available. TRIAL REGISTRATION:
      ISRCTN 16479417.

PMID- 19159479
TI  - An expressed sequence tag (EST) library for Drosophila serrata, a model system
      for sexual selection and climatic adaptation studies.
AB  - BACKGROUND: The native Australian fly Drosophila serrata belongs to the highly
      speciose montium subgroup of the melanogaster species group. It has recently
      emerged as an excellent model system with which to address a number of important
      questions, including the evolution of traits under sexual selection and traits
      involved in climatic adaptation along latitudinal gradients. Understanding the
      molecular genetic basis of such traits has been limited by a lack of genomic
      resources for this species. Here, we present the first expressed sequence tag
      (EST) collection for D. serrata that will enable the identification of genes
      underlying sexually-selected phenotypes and physiological responses to
      environmental change and may help resolve controversial phylogenetic
      relationships within the montium subgroup. RESULTS: A normalized cDNA library was
      constructed from whole fly bodies at several developmental stages, including
      larvae and adults. Assembly of 11,616 clones sequenced from the 3' end allowed us
      to identify 6,607 unique contigs, of which at least 90% encoded peptides. Partial
      transcripts were discovered from a variety of genes of evolutionary interest by
      BLASTing contigs against the 12 Drosophila genomes currently sequenced. By
      incorporating into the cDNA library multiple individuals from populations
      spanning a large portion of the geographical range of D. serrata, we were able to
      identify 11,057 putative single nucleotide polymorphisms (SNPs), with 278
      different contigs having at least one "double hit" SNP that is highly likely to
      be a real polymorphism. At least 394 EST-associated microsatellite markers,
      representing 355 different contigs, were also found, providing an additional set
      of genetic markers. The assembled EST library is available online at
      http://www.chenowethlab.org/serrata/index.cgi. CONCLUSION: We have provided the
      first gene collection and largest set of polymorphic genetic markers, to date,
      for the fly D. serrata. The EST collection will provide much needed genomic
      resources for this model species and facilitate comparative evolutionary studies
      within the montium subgroup of the D. melanogaster lineage.

PMID- 19159480
TI  - Preliminary data concerning the reliability and psychometric properties of the
      Greek translation of the 20-item Subjective Well-Being Under Neuroleptic
      Treatment Scale (SWN-20).
AB  - BACKGROUND: The 20-item Subjective Well-Being Under Neuroleptic Treatment Scale
      (SWN-20) is a self-report scale developed in order to assess the well-being of
      patients receiving antipsychotic medication independent of the improvement in
      their psychotic symptoms. The current study reports on the reliability and the
      psychometric properties of the Greek translation of the SWN-20. METHODS: A total
      of 100 inpatients or outpatients with schizophrenia (79 males and 21 females,
      aged 42.6 +/- 11.35 years old) from 3 different facilities were assessed with the
      Positive and Negative Symptoms Scale (PANSS), the Calgary Depression Scale and
      the Simpson-Angus Scale, and completed the SWN-20. The statistical analysis
      included the calculation of Pearson product moment correlation coefficient, the
      Cronbach alpha and factor analysis with Varimax normalised rotation. RESULTS: The
      SWN-20 had an alpha value equal to 0.79 and all the items were equal. The factor
      analysis revealed the presence of seven factors explaining 66% of total variance.
      The correlation matrix revealed a moderate relationship of the SWN-20 and its
      factors with the PANSS-Negative (PANSS-N), PANSS-General Psychopathology (PANSS
      G), the Simpson-Angus and the Calgary scales, and no relationship to age,
      education and income class. DISCUSSION: The Greek translation of the SWN-20 is
      reliable, with psychometric properties close to the original scale.

PMID- 19159482
TI  - Generation and analysis of expressed sequence tags from six developing xylem
      libraries in Pinus radiata D. Don.
AB  - BACKGROUND: Wood is a major renewable natural resource for the timber, fibre and
      bioenergy industry. Pinus radiata D. Don is the most important commercial
      plantation tree species in Australia and several other countries; however,
      genomic resources for this species are very limited in public databases. Our
      primary objective was to sequence a large number of expressed sequence tags
      (ESTs) from genes involved in wood formation in radiata pine. RESULTS: Six
      developing xylem cDNA libraries were constructed from earlywood and latewood
      tissues sampled at juvenile (7 yrs), transition (11 yrs) and mature (30 yrs)
      ages, respectively. These xylem tissues represent six typical development stages
      in a rotation period of radiata pine. A total of 6,389 high quality ESTs were
      collected from 5,952 cDNA clones. Assembly of 5,952 ESTs from 5' end sequences
      generated 3,304 unigenes including 952 contigs and 2,352 singletons. About 97.0%
      of the 5,952 ESTs and 96.1% of the unigenes have matches in the UniProt and TIGR
      databases. Of the 3,174 unigenes with matches, 42.9% were not assigned GO (Gene
      Ontology) terms and their functions are unknown or unclassified. More than half
      (52.1%) of the 5,952 ESTs have matches in the Pfam database and represent 772
      known protein families. About 18.0% of the 5,952 ESTs matched cell wall related
      genes in the MAIZEWALL database, representing all 18 categories, 91 of all 174
      families and possibly 557 genes. Fifteen cell wall-related genes are ranked in
      the 30 most abundant genes, including CesA, tubulin, AGP, SAMS, actin, laccase,
      CCoAMT, MetE, phytocyanin, pectate lyase, cellulase, SuSy, expansin, chitinase
      and UDP-glucose dehydrogenase. Based on the PlantTFDB database 41 of the 64
      transcription factor families in the poplar genome were identified as being
      involved in radiata pine wood formation. Comparative analysis of GO term
      abundance revealed a distinct transcriptome in juvenile earlywood formation
      compared to other stages of wood development. CONCLUSION: The first large scale
      genomic resource in radiata pine was generated from six developing xylem cDNA
      libraries. Cell wall-related genes and transcription factors were identified.
      Juvenile earlywood has a distinct transcriptome, which is likely to contribute to
      the undesirable properties of juvenile wood in radiata pine. The publicly
      available resource of radiata pine will also be valuable for gene function
      studies and comparative genomics in forest trees.

PMID- 19159483
TI  - Cost-effectiveness of Rotavirus vaccination in Vietnam.
AB  - BACKGROUND: Rotavirus is the most common cause of severe diarrhea leading to
      hospitalization or disease-specific death among young children. New rotavirus
      vaccines have recently been approved. Some previous studies have provided broad
      qualitative insights into the health and economic consequences of introducing the
      vaccines into low-income countries, representing several features of rotavirus
      infection, such as varying degrees of severity and age-dependency of clinical
      manifestation, in their model-based analyses. We extend this work to reflect
      additional features of rotavirus (e.g., the possibility of reinfection and
      varying degrees of partial immunity conferred by natural infection), and assess
      the influence of the features on the cost-effectiveness of rotavirus vaccination.
      METHODS: We developed a Markov model that reflects key features of rotavirus
      infection, using the most recent data available. We applied the model to the 2004
      Vietnamese birth cohort and re-evaluated the cost-effectiveness (2004 US dollars
      per disability-adjusted life year [DALY]) of rotavirus vaccination (Rotarix)
      compared to no vaccination, from both societal and health care system
      perspectives. We conducted univariate sensitivity analyses and also performed a
      probabilistic sensitivity analysis, based on Monte Carlo simulations drawing
      parameter values from the distributions assigned to key uncertain parameters.
      RESULTS: Rotavirus vaccination would not completely protect young children
      against rotavirus infection due to the partial nature of vaccine immunity, but
      would effectively reduce severe cases of rotavirus gastroenteritis (outpatient
      visits, hospitalizations, or deaths) by about 67% over the first 5 years of life.
      Under base-case assumptions (94% coverage and $5 per dose), the incremental cost
      per DALY averted from vaccination compared to no vaccination would be $540 from
      the societal perspective and $550 from the health care system perspective.
      CONCLUSION: Introducing rotavirus vaccines would be a cost-effective public
      health intervention in Vietnam. However, given the uncertainty about vaccine
      efficacy and potential changes in rotavirus epidemiology in local settings,
      further clinical research and re-evaluation of rotavirus vaccination programs may
      be necessary as new information emerges.

PMID- 19159484
TI  - Using least median of squares for structural superposition of flexible proteins.
AB  - BACKGROUND: The conventional superposition methods use an ordinary least squares
      (LS) fit for structural comparison of two different conformations of the same
      protein. The main problem of the LS fit that it is sensitive to outliers, i.e.
      large displacements of the original structures superimposed. RESULTS: To overcome
      this problem, we present a new algorithm to overlap two protein conformations by
      their atomic coordinates using a robust statistics technique: least median of
      squares (LMS). In order to effectively approximate the LMS optimization, the
      forward search technique is utilized. Our algorithm can automatically detect and
      superimpose the rigid core regions of two conformations with small or large
      displacements. In contrast, most existing superposition techniques strongly
      depend on the initial LS estimating for the entire atom sets of proteins. They
      may fail on structural superposition of two conformations with large
      displacements. The presented LMS fit can be considered as an alternative and
      complementary tool for structural superposition. CONCLUSION: The proposed
      algorithm is robust and does not require any prior knowledge of the flexible
      regions. Furthermore, we show that the LMS fit can be extended to multiple level
      superposition between two conformations with several rigid domains. Our fit tool
      has produced successful superpositions when applied to proteins for which two
      conformations are known. The binary executable program for Windows platform,
      tested examples, and database are available from
      https://engineering.purdue.edu/PRECISE/LMSfit.

PMID- 19159485
TI  - Regulatory axes on food advertising to children on television.
AB  - This article describes and evaluates some of the criteria on the basis of which
      food advertising to children on television could be regulated, including controls
      that revolve around the type of television programme, the type of product, the
      target audience and the time of day. Each of these criteria potentially functions
      as a conceptual device or "axis" around which regulation rotates. The article
      considers examples from a variety of jurisdictions around the world, including
      Sweden and Quebec. The article argues that restrictions centring on the time of
      day when a substantial proportion of children are expected to be watching
      television are likely to be the easiest for consumers to understand, and the most
      effective in limiting children's exposure to advertising.

PMID- 19159481
TI  - Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on
      early gene expression for molecules associated with metabolism, signaling and
      regulation in central nervous system mixed glial cell cultures.
AB  - BACKGROUND: Cytokines secreted by immune cells and activated glia play central
      roles in both the pathogenesis of and protection from damage to the central
      nervous system (CNS) in multiple sclerosis (MS). METHODS: We have used gene array
      analysis to identify the initial direct effects of cytokines on CNS glia by
      comparing changes in early gene expression in CNS glial cultures treated for 6
      hours with cytokines typical of those secreted by Th1 and Th2 lymphocytes and
      monocyte/macrophages (M/M). RESULTS: In two previous papers, we summarized
      effects of these cytokines on immune-related molecules, and on neural and glial
      related proteins, including neurotrophins, growth factors and structural
      proteins. In this paper, we present the effects of the cytokines on molecules
      involved in metabolism, signaling and regulatory mechanisms in CNS glia. Many of
      the changes in gene expression were similar to those seen in ischemic
      preconditioning and in early inflammatory lesions in experimental autoimmune
      encephalomyelitis (EAE), related to ion homeostasis, mitochondrial function,
      neurotransmission, vitamin D metabolism and a variety of transcription factors
      and signaling pathways. Among the most prominent changes, all three cytokine
      mixtures markedly downregulated the dopamine D3 receptor, while Th1 and Th2
      cytokines downregulated neuropeptide Y receptor 5. An unexpected finding was the
      large number of changes related to lipid metabolism, including several suggesting
      a switch from diacylglycerol to phosphatidyl inositol mediated signaling
      pathways. Using QRT-PCR we validated the results for regulation of genes for
      iNOS, arginase and P glycoprotein/multi-drug resistance protein 1 (MDR1) seen at
      6 hours with microarray. CONCLUSION: Each of the three cytokine mixtures
      differentially regulated gene expression related to metabolism and signaling that
      may play roles in the pathogenesis of MS, most notably with regard to
      mitochondrial function and neurotransmitter signaling in glia.

PMID- 19159486
TI  - Atomic structures and functional implications of the archaeal RecQ-like helicase
      Hjm.
AB  - BACKGROUND: Pyrococcus furiosus Hjm (PfuHjm) is a structure-specific DNA helicase
      that was originally identified by in vitro screening for Holliday junction
      migration activity. It belongs to helicase superfamily 2, and shares homology
      with the human DNA polymerase Theta (PolTheta), HEL308, and Drosophila Mus308
      proteins, which are involved in DNA repair. Previous biochemical and genetic
      analyses revealed that PfuHjm preferentially binds to fork-related Y-structured
      DNAs and unwinds their double-stranded regions, suggesting that this helicase is
      a functional counterpart of the bacterial RecQ helicase, which is essential for
      genome maintenance. Elucidation of the DNA unwinding and translocation mechanisms
      by PfuHjm will require its three-dimensional structure at atomic resolution.
      RESULTS: We determined the crystal structures of PfuHjm, in two apo-states and
      two nucleotide bound forms, at resolutions of 2.0-2.7 A. The overall structures
      and the local conformations around the nucleotide binding sites are almost the
      same, including the side-chain conformations, irrespective of the nucleotide
      binding states. The architecture of Hjm was similar to that of Archaeoglobus
      fulgidus Hel308 complexed with DNA. An Hjm-DNA complex model, constructed by
      fitting the five domains of Hjm onto the corresponding Hel308 domains, indicated
      that the interaction of Hjm with DNA is similar to that of Hel308. Notably,
      sulphate ions bound to Hjm lie on the putative DNA binding surfaces. Electron
      microscopic analysis of an Hjm-DNA complex revealed substantial flexibility of
      the double stranded region of DNA, presumably due to particularly weak protein
      DNA interactions. Our present structures allowed reasonable homology model
      building of the helicase region of human PolTheta, indicating the strong
      conformational conservation between archaea and eukarya. CONCLUSION: The detailed
      comparison between our DNA-free PfuHjm structure and the structure of Hel308
      complexed with DNA suggests similar DNA unwinding and translocation mechanisms,
      which could be generalized to all of the members in the same family. Structural
      comparison also implied a minor rearrangement of the five domains during DNA
      unwinding reaction. The unexpected small contact between the DNA duplex region
      and the enzyme appears to be advantageous for processive helicase activity.

PMID- 19159487
TI  - Susceptibility to intestinal infection and diarrhoea in Zambian adults in
      relation to HIV status and CD4 count.
AB  - BACKGROUND: The HIV epidemic in sub-Saharan Africa has had a major impact on
      infectious disease, and there is currently great interest in the impact of HIV on
      intestinal barrier function. A three year longitudinal cohort study in a shanty
      compound in Lusaka, Zambia, carried out before anti-retroviral therapy was widely
      available, was used to assess the impact of HIV on susceptibility to intestinal
      infectious disease. We measured the incidence and seasonality of intestinal
      infection and diarrhoea, aggregation of disease in susceptible individuals,
      clustering by co-habitation and genetic relatedness, and the disease-to-infection
      ratio. METHODS: Adults living in a small section of Misisi, Lusaka, were
      interviewed every two weeks to ascertain the incidence of diarrhoea. Monthly
      stool samples were analysed for selected pathogens. HIV status and CD4 count were
      determined annually. RESULTS: HIV seroprevalence was 31% and the prevalence of
      immunosuppression (CD4 count 200 cells/microL or less) was 10%. Diarrhoea
      incidence was 1.1 episodes per year and the Incidence Rate Ratio for HIV
      infection was 2.4 (95%CI 1.7-3.3; p < 0.001). The disease-to-infection ratio was
      increased at all stages of HIV infection. Aggregation of diarrhoea in susceptible
      individuals was observed irrespective of immunosuppression, but there was little
      evidence of clustering by co-habitation or genetic relatedness. There was no
      evidence of aggregation of asymptomatic infections. CONCLUSION: HIV has an impact
      on intestinal infection at all stages, with an increased disease-to-infection
      ratio. The aggregation of disease in susceptible individuals irrespective of CD4
      count suggests that this phenomenon is not a function of cell mediated immunity.

PMID- 19159488
TI  - BEAP: The BLAST Extension and Alignment Program- a tool for contig construction
      and analysis of preliminary genome sequence.
AB  - BACKGROUND: Fine-mapping projects require a high density of SNP markers and
      positional candidate gene sequences. In species with incomplete genomic sequence,
      the DNA sequences needed to generate markers for fine-mapping within a linkage
      analysis confidence interval may be available but may not have been assembled. To
      manually piece these sequences together is laborious and costly. Moreover,
      annotation and assembly of short, incomplete DNA sequences is time consuming and
      not always straightforward. FINDINGS: We have created a tool called BEAP that
      combines BLAST and CAP3 to retrieve sequences and construct contigs for localized
      genomic regions in species with unfinished sequence drafts. The rational is that
      a completed genome can be used as a template to query target genomic sequence for
      closing the gaps or extending contig sequence length in species whose genome is
      incomplete on the basis that good homology exists. Each user must define what
      template sequence is appropriate based on comparative mapping data such as
      radiation hybrid (RH) maps or other evidence linking the gene sequence of the
      template species to the target species. CONCLUSION: The BEAP software creates
      contigs suitable for discovery of orthologous genes for positional cloning. The
      resulting sequence alignments can be viewed graphically with a Java graphical
      user interface (GUI), allowing users to evaluate contig sequence quality and
      predict SNPs. We demonstrate the successful use of BEAP to generate genomic
      template sequence for positional cloning of the Angus dwarfism mutation. The
      software is available for free online for use on UNIX systems at
      http://www.animalgenome.org/bioinfo/tools/beap/.

PMID- 19159489
TI  - Prevalence, sources, and predictors of soy consumption in breast cancer.
AB  - BACKGROUND: A number of components in soy appear to have anticancer properties,
      including the isoflavones, genistein and daidzein. The use of soy by women with
      breast cancer is now being questioned because of the estrogen-like effects of
      isoflavones and possible interactions with tamoxifen. Clinicians providing
      nutrition counseling to these women are concerned because the availability of soy
      foods has increased dramatically in the past few years. The goal of this study
      was to quantify the intake of isoflavones in women with breast cancer. METHODS: A
      cross-sectional study of 100 women with breast cancer treated at Cancer Treatment
      Centers of America(R) between 09/03 and 02/04. Each patient completed a soy food
      frequency questionnaire (FFQ) that was scored by Fred Hutchinson Cancer Research
      Center. Demographic and clinical predictors of soy intake were evaluated using
      one-way non-parametric Mann Whitney test and non-parametric spearman's rank
      correlation. RESULTS: Mean age was 50.5 years (std. dev. = 9.4; range 31-70) and
      mean BMI was 27.3 kg/m2 (std. dev. = 6.75; range 17-59). Genistein and Daidzein
      consumption was limited to 65 patients with a mean intake of 11.6 mg/day (std.
      dev. = 21.9; range 0-97.4) and 7.6 mg/day (std. dev. = 14.1; range 0-68.9)
      respectively. Soy milk (37%) and pills containing soy, isoflavones, or "natural"
      estrogen (24%) were the two biggest contributors to isoflavone intake.
      CONCLUSION: Our study suggests that the isoflavone intake of breast cancer
      patients at our hospital was quite variable. Thirty-five patients reported no soy
      intake. The mean daily intake of 11.6 mg genistein and 7.4 mg daidzein, is the
      equivalent of less than 1/4 cup of tofu per day. This amount is higher than what
      has been previously reported in non-Asian American women.

PMID- 19159490
TI  - Positive correlation between gene coexpression and positional clustering in the
      zebrafish genome.
AB  - BACKGROUND: Co-expressing genes tend to cluster in eukaryotic genomes. This paper
      analyzes correlation between the proximity of eukaryotic genes and their
      transcriptional expression pattern in the zebrafish (Danio rerio) genome using
      available microarray data and gene annotation. RESULTS: The analyses show that
      neighbouring genes are significantly coexpressed in the zebrafish genome, and the
      coexpression level is influenced by the intergenic distance and transcription
      orientation. This fact is further supported by examining the coexpression level
      of genes within positional clusters in the neighbourhood model. There is a
      positive correlation between gene coexpression and positional clustering in the
      zebrafish genome. CONCLUSION: The study provides another piece of evidence for
      the hypothesis that coexpressed genes do cluster in the eukaryotic genomes.

PMID- 19159491
TI  - Role of sgcR3 in positive regulation of enediyne antibiotic C-1027 production of
      Streptomyces globisporus C-1027.
AB  - BACKGROUND: C-1027, produced by Streptomyces globisporus C-1027, is one of the
      most potent antitumoral agents. The biosynthetic gene cluster of C-1027,
      previously cloned and sequenced, contains at least three putative regulatory
      genes, i.e. sgcR1, sgcR2 and sgcR3. The predicted gene products of these genes
      share sequence similarities to StrR, regulators of AraC/XylS family and TylR. The
      purpose of this study was to investigate the role of sgcR3 in C-1027
      biosynthesis. RESULTS: Overexpression of sgcR3 in S. globisporus C-1027 resulted
      in a 30-40% increase in C-1027 production. Consistent with this, disruption of
      sgcR3 abolished C-1027 production. Complementation of the sgcR3-disrupted strain
      R3KO with intact sgcR3 gene could restore C-1027 production. The results from
      real time RT-PCR analysis in R3KO mutant and wild type strain indicated that not
      only transcripts of biosynthetic structural genes such as sgcA1 and sgcC4, but
      also putative regulatory genes, sgcR1 and sgcR2, were significantly decreased in
      R3KO mutant. The cross-complementation studies showed that sgcR1R2 could
      functionally complement sgcR3 disruption in trans. Purified N-terminal His10
      tagged SgcR3 showed specific DNA-binding activity to the promoter region of
      sgcR1R2. CONCLUSION: The role of SgcR3 has been proved to be a positive regulator
      of C-1027 biosynthesis in S. globisporus C-1027. SgcR3 occupies a higher level
      than SgcR1 and SgcR2 in the regulatory hierarchy that controls C-1027 production
      and activates the transcription of sgcR1 and sgcR2 by binding directly to the
      promoter region of sgcR1R2.

PMID- 19159493
TI  - Minute ampullary carcinoid tumor with lymph node metastases: a case report and
      review of literature.
AB  - BACKGROUND: Carcinoid tumors are usually considered to have a low degree of
      malignancy and show slow progression. One of the factors indicating the
      malignancy of these tumors is their size, and small ampullary carcinoid tumors
      have been sometimes treated by endoscopic resection. CASE PRESENTATION: We report
      a case of a 63-year-old woman with a minute ampullary carcinoid tumor that was 7
      mm in diameter, but was associated with 2 peripancreatic lymph node metastases.
      Mild elevation of liver enzymes was found at her regular medical check-up.
      Computed tomography (CT) revealed a markedly dilated common bile duct (CBD) and
      two enlarged peripancreatic lymph nodes. Endoscopy showed that the ampulla was
      slightly enlarged by a submucosal tumor. The biopsy specimen revealed tumor cells
      that showed monotonous proliferation suggestive of a carcinoid tumor. She
      underwent a pylorus-preserving whipple resection with lymph node dissection. The
      resected lesion was a small submucosal tumor (7 mm in diameter) at the ampulla,
      with metastasis to 2 peripancreatic lymph nodes, and it was diagnosed as a
      malignant carcinoid tumor. CONCLUSION: Recently there have been some reports of
      endoscopic ampullectomy for small carcinoid tumors. However, this case suggests
      that attention should be paid to the possibility of lymph node metastases as well
      as that of regional infiltration of the tumor even for minute ampullary carcinoid
      tumors to provide the best chance for cure.

PMID- 19159492
TI  - The impact of demographic and risk factor changes on coronary heart disease
      deaths in Beijing, 1999-2010.
AB  - BACKGROUND: Recent, dramatic increases in coronary heart disease (CHD) mortality
      in China can be mostly explained by adverse changes in major cardiovascular risk
      factors. Our study aimed to assess the potential impact of subsequent changes in
      risk factors and population ageing on CHD deaths in Beijing between 1999 and
      2010. METHODS: The previously validated IMPACT model was used to estimate the CHD
      deaths expected in 2010, with treatment uptakes being held constant at levels
      measured in 1999, comparing three scenarios: a) taking into account the ageing of
      the population but assuming no further changes in major risk factor levels from
      1999 or, b) if recent risk factor trends continued until 2010 or, c) if there was
      a 0.5% annual reduction in each risk factor. RESULTS: Population ageing alone
      would result in approximately 1990 additional deaths in 2010 compared with 1999,
      representing an increase of 27%. Continuation of current risk factor trends would
      result in approximately 3,015 extra deaths in 2010, [a 40% increase]; three
      quarters of this increase would be attributable to rises in total cholesterol
      levels. Thus, demographic changes and worsening risk factors would together
      result in a 67% increase in CHD deaths. Conversely, assumed 0.5% annual
      reductions in risk factors (a mean population level decline of 0.3 mmol/L for
      total cholesterol in both genders, and smoking prevalence declining by 3.0% for
      men and 4.1% for women, body mass index by 1.3 kg/m2 for men and 1.4 kg/m2 for
      women, diabetes prevalence by 0.4% in both genders, and diastolic blood pressure
      by 4.7 mmHg for men and 4.4 mmHg for women) would result in some 3,730 fewer
      deaths, representing a 23% decrease overall. These findings remained consistent
      in sensitivity analyses. CONCLUSION: CHD death rates are continuing to rise in
      Beijing. This reflects worsening risk factor levels, compounded by demographic
      trends. However, the adverse impact of population ageing on CHD burden could be
      completely offset by eminently feasible improvements in diet and smoking.

PMID- 19159495
TI  - Rising cesarean delivery rates: the impact of cesarean delivery on maternal
      request.
AB  - Primary and repeat cesarean delivery rates have reached their highest levels both
      nationally and internationally, with 30.3% of live births in the United States
      being cesarean deliveries. Some cite the increase in cesarean delivery on
      maternal request (CDMR) as a contributing factor, although data have yet to
      confirm this. Concern about the rising number of cesareans performed, and the
      lack of clear knowledge about health outcomes for both mother and neonate as a
      result of this trend prompted the National Institute of Child Health and Human
      Development and the Office of Medical Applications of Research of the National
      Institutes of Health to convene a State-of-the-Science Conference on the topic of
      CDMR from March 27 to 29, 2006. Before this conference, a study was conducted by
      the American College of Obstetricians and Gynecologists to assess practice
      patterns and opinions related to CDMR among obstetrician-gynecologists. It was
      found that most obstetrician-gynecologists recognized an increased demand for
      CDMR in their practices. Conclusions from this study and the conference are
      reviewed along with more recent research on this topic.

PMID- 19159494
TI  - Molecular models of human P-glycoprotein in two different catalytic states.
AB  - BACKGROUND: P-glycoprotein belongs to the family of ATP-binding cassette proteins
      which hydrolyze ATP to catalyse the translocation of their substrates through
      membranes. This protein extrudes a large range of components out of cells,
      especially therapeutic agents causing a phenomenon known as multidrug resistance.
      Because of its clinical interest, its activity and transport function have been
      largely characterized by various biochemical studies. In the absence of a high
      resolution structure of P-glycoprotein, homology modeling is a useful tool to
      help interpretation of experimental data and potentially guide experimental
      studies. RESULTS: We present here three-dimensional models of two different
      catalytic states of P-glycoprotein that were developed based on the crystal
      structures of two bacterial multidrug transporters. Our models are supported by a
      large body of biochemical data. Measured inter-residue distances correlate well
      with distances derived from cross-linking data. The nucleotide-free model
      features a large cavity detected in the protein core into which ligands of
      different size were successfully docked. The locations of docked ligands compare
      favorably with those suggested by drug binding site mutants. CONCLUSION: Our
      models can interpret the effects of several mutants in the nucleotide-binding
      domains (NBDs), within the transmembrane domains (TMDs) or at the NBD:TMD
      interface. The docking results suggest that the protein has multiple binding
      sites in agreement with experimental evidence. The nucleotide-bound models are
      exploited to propose different pathways of signal transmission upon ATP
      binding/hydrolysis which could lead to the elaboration of conformational changes
      needed for substrate translocation. We identified a cluster of aromatic residues
      located at the interface between the NBD and the TMD in opposite halves of the
      molecule which may contribute to this signal transmission. Our models may
      characterize different steps in the catalytic cycle and may be important tools to
      understand the structure-function relationship of P-glycoprotein.

PMID- 19159496
TI  - Clinical implications of ovarian reserve testing.
AB  - Serum and urinary markers of ovarian reserve, follicular phase inhibin B,
      follicle stimulating hormone, and antimullerian hormone levels, are
      physiologically associated with ovarian aging, decline with chronologic age, and
      appear to predict later stages of reproductive aging including the menopause
      transition and menopause. In infertile women, they can be used to predict low
      oocyte yield and treatment failure in women undergoing in vitro fertilization.
      These markers seem to be affected by common ovarian toxicants, such as smoking,
      which advance the age at menopause. Although available for commercial use, home
      test kits have not been shown to predict fertility or infertility in the general
      population. Clinical use of these markers is limited by the variety of assays,
      lack of definitive thresholds, and their intercycle variability in older women.
      Results should be conveyed with caution when highly discrepant with age, in the
      obese, and in women with irregular menstrual cycles. Further research is needed
      to assess their predictive value for determining fertility in the general
      population.

PMID- 19159497
TI  - Carbetocin for the prevention of postpartum hemorrhage: a systematic review.
AB  - The objective of this review was to evaluate the efficacy and safety of
      carbetocin in the prevention of postpartum hemorrhage. All trials found during a
      targeted Medline and Cochrane database search were screened for eligibility.
      Outcome measures were estimated blood loss, uterine tone, amount and type of
      lochia, fundal position after delivery (number of centimeters above or below the
      umbilicus), side-effects, adverse effects, vital signs, levels of
      hemoglobin/hematocrit before delivery compared with 24 or 48 hours postpartum,
      the need for additional uterotonic therapy, and/or uterine massage and duration
      of the third stage of labor. The retrieved studies were difficult to compare
      because of differences in study design and outcome. We conclude that carbetocin
      probably is as effective as oxytocin or syntometrine in the prophylactic
      management of the third stage of labor. Also carbetocin has a similar safety
      profile to oxytocin, which is now used as a standard prophylactic treatment.
      However, more research on this subject is needed.

PMID- 19159498
TI  - Analyzing haplodiploid inheritance of insecticide resistance in whitefly
      biotypes.
AB  - We developed new methods for analyzing inheritance of insecticide resistance in
      haplodiploid arthropods and applied them to elucidate resistance of the whitefly
      Bemisia tabaci (Gennadius) to an insect growth regulator, pyriproxyfen. Two
      invasive biotypes of this devastating crop pest, the B biotype in Arizona and the
      Q biotype in Israel, have evolved resistance to pyriproxyfen. Here, we
      incorporated data from laboratory bioassays and crossing procedures exploiting
      haplodiploidy into statistical and analytical models to estimate the number of
      loci affecting pyriproxyfen resistance in strains of both biotypes. In tests with
      models of one to ten loci, the best fit between expected and observed mortality
      occurred with a two-locus model for the B biotype strain (QC-02) and for one- and
      two-locus models for the Q biotype strain (Pyri-R). The estimated minimum number
      of loci affecting resistance was 1.6 for the B biotype strain and 1.0 for the Q
      biotype strain. The methods used here can be applied to insecticide resistance
      and other traits in haplodiploid arthropods.

PMID- 19159499
TI  - Investigating the diet of the omnivorous mirid Dicyphus hesperus using stable
      isotopes.
AB  - Omnivory involves numerous feeding relationships and a complex web of
      interactions. When using omnivores in biocontrol, these interactions need to be
      understood to maximize feeding on the target species and minimize non-target
      interactions. Dicyphus hesperus is used along with Encarsia formosa for
      biocontrol of whiteflies in greenhouse tomato crops. Dicyphus hesperus is a
      generalist omnivore which feeds on all components of the system. To quantify
      these interactions, stable isotope analysis was used to identify trophic position
      with nitrogen isotopes (delta15N) and plant sources with carbon isotopes
      (delta13C). Feeding trials were used to establish baseline isotopic data for D.
      hesperus and their diet, including Verbascum thapsus, an alternative plant food.
      Cage trials were used to monitor population abundances and the isotopic signature
      of D. hesperus. In feeding trials, D. hesperus were enriched relative to their
      food, suggesting an elevated trophic position. However, large amounts of isotopic
      variation were found within all diet components, with only V. thapsus exhibiting
      a distinct signature. In cage trials, the average delta15N and delta13C of the
      omnivore declined over time, coinciding with declines in total available prey,
      though it may be confounded by changes in temperature. The range of delta13C, but
      not the range of delta15N, also declined over time. This suggests a change in the
      plant source within the diet, but also some unquantified variability within the
      population. We suggest that diet variability exists within D. hesperus
      populations, declining as prey become less abundant.

PMID- 19159500
TI  - A new modelling approach to insect reproduction with same-shape reproduction
      distribution and rate summation: with particular reference to Russian wheat
      aphid.
AB  - Same-shape distribution model and rate summation approach are widely used to
      describe the insect developmental process. In this approach, by integrating a
      nonlinear deterministic developmental rate model and a probabilistic same-shape
      distribution model, the proportion of the cohort completing development is
      quantified as a function of accumulating developmental rates, which themselves
      are temperature dependent. This method is considered to be more accurate in
      modelling insect phenology because it can address a well-known biological fact,
      individual variability, that insect individual developmental rates respond to
      temperature differently, and because rate-summation essentially simulates
      developmental rates under variable temperatures instead of constant temperatures.
      By comparing insect development and reproduction with respect to their responses
      to temperatures, we argue for the extension of the same-shape and rate-summation
      approaches to modelling insect reproduction process under variable temperatures.
      We justify our arguments by the fact that individual variation universally exists
      in almost all biological characteristics, and the phenomenon that insect
      development and reproduction respond to temperature very similarly, which is
      supported by some endocrinological evidences reported in literature. In addition,
      the approach for testing the applicability of the original same-shape
      developmental modelling, experimentally verifying the sameness of the same-shape
      curves or that the shape of the curves is invariant with respect to the
      temperature regimes, equally applies to our extended version for reproduction
      modelling. We successfully tested the extension and its applicability with our
      experimental data of 1800 Russian wheat aphids' (RWA) (Diuraphis noxia
      (Mordvilko)) reproduction under various temperature and plant growth stage
      regimes. We also extended Taylor's (1981) nonlinear model for insect development
      to describe RWA mean (median) nymphal production under different temperatures and
      barley plant growth stages. Three same-shape distribution models, Weibull
      distribution, Stinner's model and logistic model, are used to construct the same
      shape reproduction distribution models for RWA. The extensions performed in this
      paper contribute a new modelling approach for predicting insect reproduction
      under field variable temperatures and plant growth stages. The prediction model
      can be parameterized with data from typical laboratory demography experiments and
      further integrated into simulation models for insect population dynamics.
      Finally, we discussed why the sameness test of the same-shape distribution curves
      is sufficient in validating the approach and proposed a strategy for dealing with
      exceptional cases where the sameness test fails.

PMID- 19159501
TI  - The first account of the mating disruption technique for the control of
      California red scale, Aonidiella aurantii Maskell (Homoptera: Diaspididae) using
      new biodegradable dispensers.
AB  - Semiochemical-based pest management programs have been increasingly used to
      provide environmentally friendly methods for the control of major insect pests.
      The efficacy of the mating disruption technique has been demonstrated for several
      moth pests. Unfortunately, not many experiments on mating disruption to control
      diaspididae species have been documented. In this work, biodegradable dispensers
      for mating disruption with increasing pheromone loads were used in order to study
      the potential of this technique for the control of Aonidiella aurantii Maskell.
      Field trial results demonstrated that dispensers loaded with 50 mg (a.i.) (20 g
      ha-1) and 100 mg (a.i.) (40 g ha-1) of sex pheromone were the most suitable,
      achieving significant reductions in male catches, compared to an untreated plot.
      In treated plots, virtually a 70% reduction in damage to fruit was recorded.
      Pheromone release profiles of all the dispensers were also studied under field
      conditions. We found that emission values >250 microg day-1 were the most
      suitable. This study suggests a new biodegradable dispenser capable of
      interfering with normal A. aurantii chemical communication. The use of mating
      disruption as a control method against A. aurantii is discussed.

PMID- 19159502
TI  - Spatiotemporal within-plant distribution of the spider mite Tetranychus urticae
      and associated specialist and generalist predators.
AB  - Predators are important determinants of the spatiotemporal distribution of prey
      within a given habitat. The predator effects may vary with diet specialisation,
      the associated risk posed to prey and, if multiple predators are present, the
      predator-predator interactions. We examined the spatiotemporal distribution of
      the herbivorous spider mite Tetranychus urticae and the associated specialist and
      generalist predators Phytoseiulus persimilis and Neoseiulus californicus on bean
      plants. Tetranychus urticae is a key pest on numerous agricultural crops. Both
      predators are used singly and in combination for biological control of spider
      mites. Population development and within-plant distribution of the spider mites
      and the predators were compared among five treatments: T. urticae without
      predators, with either predator alone and with both predators in combination at
      full and half densities. The spider mites were suppressed to zero density in both
      predator combination treatments but not in the single predator treatments. The
      predators determined the spatiotemporal distribution of the spider mites through
      density- and behaviour-mediated effects, and these effects were linked to diet
      specialisation. The specialist P. persimilis exerted stronger density-mediated
      effects on the spider mite distribution than did the generalist N. californicus.
      Either predator induced in the spider mites early upward migration on plants. The
      predators also affected each other's distribution. The aggregation level of N.
      californicus was lowered by P. persimilis but not vice versa. In combination, the
      predators were more dispersed than when alone, reducing the predator-free space
      and leading to the local extinction of T. urticae.

PMID- 19159503
TI  - Oblique rotation in correspondence analysis: a step forward in the search for the
      simplest interpretation.
AB  - Correspondence analysis (CA) is a popular method that can be used to analyse
      relationships between categorical variables. It is closely related to several
      popular multivariate analysis methods such as canonical correlation analysis and
      principal component analysis. Like principal component analysis, CA solutions can
      be rotated orthogonally as well as obliquely into a simple structure without
      affecting the total amount of explained inertia. However, some specific aspects
      of CA prevent standard rotation procedures from being applied in a
      straightforward fashion. In particular, the role played by weights assigned to
      points and dimensions and the duality of CA solutions are unique to CA. For
      orthogonal simple structure rotation, procedures recently have been proposed. In
      this paper, we construct oblique rotation methods for CA that take into account
      these specific difficulties. We illustrate the benefits of our oblique rotation
      procedure by means of two illustrative examples.

PMID- 19159504
TI  - A graded response model for measuring person reliability.
AB  - This paper extends Lumsden's fluctuation model to the graded response case and,
      from the resulting basic scaling model, develops a one-dimensional item response
      theory graded response model (GRM). Under some additional assumptions, it follows
      that the item category response functions (ICRFs) can be closely approximated by
      the ICRFs of the standard GRM with equal item discrimination. For fixed item
      locations, the item responses depend on two individual differences parameters:
      the person central location and the person reliability. Procedures for estimating
      the person parameters and for addressing the goodness of fit of the proposed
      model as compared to the standard GRM are discussed. The accuracy of the person
      estimates is assessed by means of simulation studies. Finally, all the
      developments are illustrated using three empirical examples in personality
      measurement.

PMID- 19159505
TI  - Metaphors of organ donation, social representations of the body and the opt-out
      system.
AB  - Organ donation is the only available treatment for end-stage failure of organs
      such as liver, lung, and heart and therefore increasing the number of organ
      donors is a priority for most countries. One measure that could be taken by a
      country to increase the number of organ transplants is to introduce the opt-out
      system of organ donation. Public opinion is divided on this issue and policy
      makers need to tread with caution before introducing legislation. This paper
      proposes that understanding the social representations the public has of organ
      donation is important in taking the right policy decisions. We propose here that
      an in-depth study of the views held by people on the issue is essential in this
      regard and that this can best be done by investigating the metaphors people use
      to describe organ donation, interpreted within the theory of social
      representation. In this study, the social representations of organ donation were
      investigated through five focus groups with 57 participants living in Malta.
      Analysis of the transcriptions of these focus groups yielded pertinent issues
      related to organ donation. Moreover, metaphors of organ donations and how these
      were related to social representations of the body and attitudes towards the opt
      out system are discussed. It is being suggested that these findings could be of
      relevance to the present discussion on the opt-out system in the UK and in other
      countries.

PMID- 19159506
TI  - Evidence-based selection of theories for designing behaviour change
      interventions: using methods based on theoretical construct domains to understand
      clinicians' blood transfusion behaviour.
AB  - BACKGROUND: Many theories of behaviour are potentially relevant to predictive and
      intervention studies but most studies investigate a narrow range of theories.
      Michie et al. (2005) agreed 12 'theoretical domains' from 33 theories that
      explain behaviour change. They developed a 'Theoretical Domains Interview' (TDI)
      for identifying relevant domains for specific clinical behaviours, but the
      framework has not been used for selecting theories for predictive studies. It was
      used here to investigate clinicians' transfusion behaviour in intensive care
      units (ICU). Evidence suggests that red blood cells transfusion could be reduced
      for some patients without reducing quality of care. OBJECTIVES: (1) To identify
      the domains relevant to transfusion practice in ICUs and neonatal intensive care
      units (NICUs), using the TDI. (2) To use the identified domains to select
      appropriate theories for a study predicting transfusion behaviour. METHODS: An
      adapted TDI about managing a patient with borderline haemoglobin by watching and
      waiting instead of transfusing red blood cells was used to conduct semi
      structured, one-to-one interviews with 18 intensive care consultants and
      neonatologists across the UK. RESULTS: Relevant theoretical domains were:
      knowledge, beliefs about capabilities, beliefs about consequences, social
      influences, behavioural regulation. Further analysis at the construct level
      resulted in selection of seven theoretical approaches relevant to this context:
      Knowledge-Attitude-Behaviour Model, Theory of Planned Behaviour, Social Cognitive
      Theory, Operant Learning Theory, Control Theory, Normative Model of Work Team
      Effectiveness and Action Planning Approaches. CONCLUSIONS: This study
      illustrated, the use of the TDI to identify relevant domains in a complex area of
      inpatient care. This approach is potentially valuable for selecting theories
      relevant to predictive studies and resulted in greater breadth of potential
      explanations than would be achieved if a single theoretical model had been
      adopted.

PMID- 19159507
TI  - Symptoms of depression in non-routine caregivers: the role of caregiver strain
      and burden.
AB  - OBJECTIVES: The origins and persistence of psychological morbidity in caregivers
      are not fully understood. The present analysis examined the relationship between
      the strain and burden of caregiving and depression and anxiety in a large
      community sample. Social support and sleep quality were investigated as potential
      mediators. DESIGN: Cross-sectional and prospective observational study. METHOD:
      Individuals caring for someone other than their own child (N=393) were identified
      from a population of 2,079. Caregiving strain and burden, social support, and
      sleep quality were assessed. Participants completed the hospital anxiety and
      depression scale at the same time and 5 years later. RESULTS: Caregiving strain
      and burden were associated with depression and anxiety symptoms cross
      sectionally, and with a worsening of symptoms 5 years later. Sleep quality
      appeared to mediate the cross-sectional relationships. CONCLUSIONS: The demands
      of caregiving and associated sleep disruption contribute to symptoms of
      depression and anxiety in caregivers.

PMID- 19159508
TI  - Extensor digitorum brevis and extensor hallusis brevis transplantation for
      treatment of long-standing facial paralysis.
AB  - OBJECTIVE: To evaluate the efficacy of free transplantation of denervated muscles
      and vessels in the treatment of long-standing facial paralysis. METHODS: A total
      of 26 patients with facial paralysis (10 males and 16 females, aged 16-65 years,
      mean: 47 years) were enrolled in this study to receive transplantation of
      denervated extensor digitorum brevis (EDB) and extensor hallusis brevis (EHB).
      The muscle tendon was slung to the ala nasi, the middle point of the nasolabial
      sulcus, the angulus oris and the chin to correct the nasal and oral deformity.
      The muscle belly was buried around the nerves that innervated the masseter
      muscle. Microsurgery was applied to anastomosing the tarsus lateral vessels to
      the superficial temporalis vessels. RESULTS: After operation, all the patients
      immediately obtained satisfied static appearance. The movement of the paralyzed
      corner of the mouth could be obtained one month later and the smile of the
      paralyzed side could be restored after 3 months of training. And 88% patients
      achieved perfect results, 8% obtained satisfactory results, and 4% got
      improvement 6 months after operation according to Stennert's paresis scoring
      system. CONCLUSIONS: Free transplantation of denervated muscles and vessels for
      the treatment of long-standing facial paralysis, which seldom causes atrophy or
      liquefaction of the transferred muscles, can maintain muscle viability and induce
      reliable nerve regeneration. Therefore, it is a safe and efficient treatment
      method for the patients suffering from facial paralysis.

PMID- 19159509
TI  - Analysis of 274 patients with extremity injuries caused by the Bam earthquake.
AB  - OBJECTIVE: The extremity injury pattern after a major earthquake is not well
      understood because data on this type of injury and management are limited. The
      aim of this study was to analyze the data of trauma patients with extremity
      injury in the earthquake of Bam Iran, registering 6.6 on the Richter scale.
      METHODS: We reviewed medical records of 486 patients admitted to hospitals of
      Tehran University of Medical Sciences. Among them, 274 patients sustained
      extremity injuries. This group was composed of 138 females (50.4%) and 136 males
      (49.6%) and 213 cases (77.7%) were under 40 years of age. RESULTS: Fracture was
      the major type of injury (58.4% of extremity injuries). The most common sites of
      injury were lower extremities (185 patients, 67.5% of all victims). Pelvic and
      rib fractures and abdominal injuries were the most frequently associated
      injuries. The mean ISS was 6.2+/-4.0, and 61% of the patients had ISS less than
      7. Amputation and death occurred in 2.9% and 2.5% of cases, respectively.
      CONCLUSIONS: Special attention should be given to dealing with orthopedic
      injuries in similar disasters in the future.

PMID- 19159510
TI  - Shoulder hemiarthroplasty for the treatment of complex proximal humeral
      fractures.
AB  - OBJECTIVE: To investigate the indication, perioperative announcements, selection
      of prosthesis and clinical results of shoulder hemiarthroplasty for the treatment
      of complex proximal humeral fractures. METHODS: A total of 55 patients who
      suffered from complex proximal humeral fractures were treated by shoulder
      hemiarthroplasty. The mean age was 55.6 years and mean follow-up period was 25.1
      months. The scoring system modification for hemiarthroplasty (SSMH) had been
      adopted for evaluation at the latest follow-up. RESULTS: The pain was obviously
      relieved in all patients. Fifty patients were painless and 5 patients had slight
      pain. The mean range of motion was 100 degrees (90 degrees-110 degrees) in
      abduction, 95 degrees (80 degrees-100 degrees) in forward flexion, 35 degrees (30
      degrees-40 degrees) in external rotation and internal rotation was confined at L2
      level (L1-L3). The mean SSMH score was 27.9 (24-29). Fifty patients (90.1%) were
      satisfied with the clinical outcome. CONCLUSIONS: Shoulder hemiarthroplasty is an
      effective method to treat complex proximal humeral fractures. The proper
      selection of patients and prosthesis, good operation skill and enough functional
      exercise are the key points of successful treatment.

PMID- 19159511
TI  - Protective effects of emulsified isoflurane after myocardial ischemia-reperfusion
      injury and its mechanism in rabbits.
AB  - OBJECTIVE: To evaluate the protective effects of 8% emulsified isoflurane after
      myocardial ischemia-reperfusion injury and its mechanism in rabbits. METHODS:
      Twenty-four male adult New Zealand white rabbits were anesthetized with
      intravenous injection of 30 mg/kg pentobarbital followed by 5 mg x kg(-1) x h(-1)
      infusion. All rabbits were subjected to 30 minutes of left anterior descending
      coronary artery (LAD) occlusion and 3 hours of subsequent reperfusion. Before LAD
      occlusion, the rabbits were randomly allocated into three groups for
      preconditioning treatment (eight for each group). The control group (C group)
      received intravenously 0.9% NaCl for 30 minutes. The emulsified isoflurane group
      (EI group) received 8% emulsified isoflurane intravenously till 0.64% end-tidal
      concentration for 30 minutes that was followed by a 15-minute washout period. The
      Intralipid group (IN group) received 30% Intralipid for 30 minutes. The infarcted
      area, plasma malondialdehyde (MDA) content, superoxide dismutase activity (SOD)
      and nitrite concentration after 3-hour myocardial perfusion were recorded
      simultaneously. RESULTS: For the myocardial ischemia-reperfusion injury animals,
      the infarcted size in the EI group was significantly reduced (91.9% +/- 8%) as
      compared with control group (39% +/- 6%, t=5.19, P<0.01). The plasma SOD activity
      and nitrite concentration in EI group were significantly higher than those in
      control group (t=2.82, t=8.46, P<0.05), but MDA content was lower in EI group
      than that in control group (t=2.56, P<0.05). CONCLUSIONS: The results indicate
      that emulsified isoflurane has a cardioprotection effect against ischemia
      reperfusion injury. This beneficial effect of emulsified isoflurane is probably
      through NO release and consequently by increase in antioxidation of myocardium.

PMID- 19159512
TI  - Multi-slice spiral CT 3-dimensional reconstruction technique to treat multi
      segmental degenerative spinal stenosis with traumatic instability of lower
      cervical spine.
AB  - OBJECTIVE: To study the feasibility of multi-slice spiral computed tomography
      (MSCT) 3-dimensional reconstruction technique in assisting cervical pedicle screw
      fixation (PSF) and double-door laminoplasty to treat multi-segmental degenerative
      spinal stenosis with traumatic instability (MDSTI) of lower cervical spine.
      METHODS: From September 2006 to August 2007, PSF combined with double-door
      laminoplasty was performed in 9 patients with MDSTI of lower cervical spine. MSCT
      3-dimensional reconstruction techniques, including volume rendering (VR) and
      multi-planar reconstruction (MPR), were used to assist preoperative diagnosis and
      measurement to guide the procedure. MPR was performed after operation. In coronal
      view, the degree of screw perforation was measured precisely and the different
      positions of pedicle screws were divided into three grades according to Richter's
      method. In axial view, the canal sagittal diameter and transverse area of every
      laminoplasty level were measured. RESULTS: Nine patients with MDSTI of lower
      cervical spine underwent PSF (total 44 screws). According to the classification
      of Richter, 72.7% (32/44) was in Grade 1 and 27.3% (12/44) was in Grade 2. No
      screw perforation occurred in Grade 3 and no screw revision was done for
      misplacement. No iatrogenic damage was observed. Double-door laminoplasty was
      performed in total 42 volumes. The postoperative sagittal diameter and transverse
      area of cervical spinal canal were significantly increased (P<0.05). The
      confidence intervals of mean increased ratio were 23.43%-40.65% in sagittal
      diameter and 23.18%-42.07% in transverse area. Six months after laminoplasty,
      based on MSCT axial view, complete union between "open door" and allograft bone
      was obtained in 76.19% of volumes (32/42), and allograft bone was absorbed partly
      in 23.81% (10/42). A solid union in bilateral gutters was achieved in all cases.
      They were followed up from 6 months to 1 year (mean 7.8 months). Postoperative
      neural function recovery in two cases improved 2 ASIA grade, 5 cases improved 1
      grade and 2 cases remained the same as preoperative grade. No cases had lower
      ASIA grade. CONCLUSION: Assisted with MSCT 3-dimensional reconstruction
      technique, PSF combined with double-door laminoplasty can be performed more
      safely and effectively to treat patients with MDSTI of lower cervical spine.

PMID- 19159513
TI  - Cloning, expression and functional analyses of human platelet-derived growth
      factor-B chain peptide for wound repair of cat corneal endothelial cells.
AB  - OBJECTIVE: To investigate the biological function of platelet-derived growth
      factor B (PDGF-B) on the survival and proliferation of cat corneal endothelial
      cells so as to provide bases for further studies of its role in wound repair and
      its clinical application. METHODS: Total RNA was extracted from the placenta
      tissues of healthy pregnant women undergoing hysterotokotomy and PDGF cDNA was
      obtained with reverse transcription-polymerase chain reaction (RT-PCR). The
      prokaryotic expression vector pET-PDGF-B was constructed and expressed the
      recombinant PDGF-B in Escherichia coli (E. coli) BL21 (DE3). After purification
      and refolding on Ni2+-chelation affinity chromatography (NTA) column, it was used
      to culture cat corneal endothelial cells. Cell proliferation was tested by
      modified tertrazolium salt (MTT) and flow cytometer. And the morphologic change
      and the ultrastructure were observed under an inverted phase contrast microscope,
      a scanning electron microscope and a transmission electon microscope,
      respectively. RESULTS: PDGF-B chain peptide (PDGF-BB) gene was successfully
      inserted into the prokaryotic expression vector, pET-28a (+). The purified
      recombined protein pET-PDGF-B showed a single band on sodium dodecyl sulfate
      polyacrylamide gel electropheresis (SDS-PAGE) with the molecular weight of about
      27 u, which was in agreement with the deduced value. MTT and flow cytometry
      showed that PDGF-BB promoted the survival and proliferation of cat corneal
      endothelial cells. CONCLUSIONS: The construction of recombinant prokaryotic
      expression vector pET-PDGF-B and the preparation of PDGF-BB protein provide a
      foundation for further study of the function of PDGF-BB and producing biological
      PDGF-BB protein. The expressed PDGF-BB promotes the proliferation of cultured cat
      corneal endothelial cells.

PMID- 19159514
TI  - Secondary definitive surgery for multiple injuries from Wenchuan earthquake in
      China.
AB  - OBJECTIVE: To investigate the opportune time of secondary definitive surgery for
      patients with multiple injuries from earthquakes based on the acute physiology
      and chronic health evaluation II (APACHE II) score and the principles of damage
      control. METHODS: Twenty-one patients with critical earthquake injuries were
      treated with damage control strategies, followed by medical support and surgical
      intervention to restore their physical potential in the intensive care unit
      (ICU). Successive APACHE II scoring was adopted to evaluate the
      patients'physiological status, and then, internal fixation of fractures and other
      definitive operations were performed. RESULTS: All the patients were effectively
      treated with few complications, low deformity rate and no death. CONCLUSIONS:
      Appropriate evaluation of patients?physiological potential, right decision on
      surgical time and proper operative method can reduce the rates of complications,
      disability and death for patients with critical earthquake injuries.

PMID- 19159515
TI  - Anatomic measurement of wrist scaphoid and its clinical significance.
AB  - OBJECTIVE: To provide anatomical basis for the internal fixation of scaphoid
      fractures. METHODS: The shape and vascular lake of 48 dry scaphoids and 36 wet
      scaphoids were observed. RESULTS: The data of dry bone group and wet bone group
      were as follows: the height of scaphoid tubercle were (11.28+/-0.94) mm and
      (10.35+/-1.54) mm; the thickness of scapoid waist were (12.02+/-1.90) mm and
      (11.21+/-1.20) mm; the width of scapoid waist were (10.59+/-1.11) mm and (11.34+/
      1.47) mm; the minimal thickness of the body of scapoid were (6.51+/-1.22) mm and
      (8.54+/-1.07) mm; the axis length of scapoid were (25.68+/-2.21) mm and (26.50+/
      2.56) mm; the width of epicondyle of scaphoid of distal portion, waist and
      proximal portion were (6.50+/-1.06) mm, (5.14+/-1.01) mm, (4.42+/-1.16) mm and
      (6.64+/-1.18) mm, (6.01+/-0.75) mm and (5.71+/-0.78) mm, respestively. The main
      blood vessels came from the dorsal and the radial of wrist and passed through the
      whole scaphoid along the crest of scaphoid. CONCLUSION: The internal fixation of
      scaphoid can be designed according to the anatomical data without damaging the
      articular surface and blood supply.

PMID- 19159516
TI  - Effects of CO2 pneumoperitoneum on blood flow volume of abdominal organs of
      rabbits with controlled hemorrhagic shock and liver impact injuries.
AB  - OBJECTIVE: To investigate the effects of CO(2) pneumoperitoneum on blood flow
      volume of abdominal organs of rabbits with controlled hemorrhagic shock model and
      liver impact injuries. METHODS: After controlled hemorrhagic shock and liver
      impact injuries, the rabbit model was established. Eighteen rabbits subjected to
      hemorrhagic shock and liver impact injuries were divided into 3 groups randomly
      according to the volume of lost blood: light hemorrhagic shock (blood loss volume
      was 10%, 6 ml/kg), moderate hemorrhagic shock (20%, 12 ml/kg) and severe
      hemorrhagic shock (40%, 22 ml/kg). Intraabdominal pressures of CO(2)
      pneumoperitoneum was 10 mmHg. Color-labeled microspheres were used to measure the
      blood flow volume of the liver, kidney and stomach before pneumoperitoneum at 30
      minutes and 2 hours after pneumoperitoneum and 30 minutes after deflation. And
      the mortality and hepatic traumatic condition of rabbits were recorded. RESULTS:
      Of the 18 rabbits, there were 9 with liver impact injuries at Grade I , 8 at
      Grade II and 1 at Grade III (according to AIS-2005). The mortality rate in light
      hemorrhagic shock group was 33.33%, and that in moderate or severe hemorrhagic
      shock group was 100% within 30 minutes and 2 hours after pneumoperitoneum,
      respectively. The blood flow volume in the organs detected decreased at 30
      minutes under pneumoperitoneum in light and moderate hemorrhagic shock groups. At
      the same time, the blood flow volume of the liver in moderate hemorrhagic shock
      group decreased more significantly than that in light hemorrhagic shock group.
      CONCLUSIONS: The blood flow volume of abdominal organs in rabbits is decreased
      obviously under CO(2) pneumoperitoneum, with fairly high mortality rate. It is
      believed that CO(2) pneumoperitoneum should cautiously be used in abdominal
      injury accompanied with hemorrhagic shock, especially under non-resuscitation
      conditions.

PMID- 19159517
TI  - Induction of hair follicle regeneration in rat ear by microencapsulated human
      hair dermal papilla cells.
AB  - OBJECTIVE: To induce hair follicle regeneration in rat ear by microencapsulated
      dermal papillae (DP) cells. METHODS: Intact dermal papillae were obtained from
      human scalp follicles which were digested with collagenase I. The human hair DP
      cells were encapsulated with alginate-polylysine-alginate (APA) by a high-voltage
      electric field droplet generator. The diameters of the DP cell microcapsules were
      optimized by regulating the voltage, the distance between the needle head and the
      solution surface and the injection speed. Then DP cell microencapsulations were
      xenotransplanted into ears of 20 SD rats with a novel method. One rat was killed
      every week at the postoperative 2-12 weeks and the implantation sites were
      biopsied for histological observation. RESULTS: The DP cell microencapsulations
      were found in a group of round, smooth and transparent microcapsules under a
      phase-contrast microscope. The optimal combination of parameters to obtain 0.4 mm
      DP cell microcapsules was voltage 7.0 kV, injection speed 55 mm/h, and distance
      10 mm. After 4-12 weeks, 18 of 20 DP cell microcapsule implantations had produced
      high-density hair. Histological observation indicated that both large follicles
      and sebaceous gland structures were formed in the rat ear within 3-12 weeks.
      CONCLUSIONS: These findings show that the DP cell microencapsulation maintain the
      capacity for initiating the follicle regeneration and can be considered as a
      substitute for fresh isolated dermal papillae.

PMID- 19159518
TI  - Glial implications in transplantation therapy of spinal cord injury.
AB  - Spinal cord injuries are damages that result in complete or partial loss of
      sensation and/or mobility and affect the life qualities of many patients. Their
      pathophysiology includes primary and secondary processes, which are related with
      the activation of astrocytes and microgliacytes and the degeneration of
      oligodendrocytes. Although transplantation of embryonic stem cells or neural
      progenitor cells is an attractive strategy for repair of the injured central
      nervous system (CNS), transplantation of these cells alone for acute spinal cord
      injuries has not resulted in robust axon regeneration beyond the injury sites.
      This may be due to the progenitor cells differentiating to the cell types that
      support axon growth poorly and/or their inability to modify the inhibitory
      environment of adult CNS after injury. Recent studies indicate that
      transplantation of glial progenitor cells has exhibited beneficial effects on the
      recovery and promising future for the therapy strategy of spinal cord injury. In
      this review, we summarized the data from recent literature regarding glial
      implications in transplantation therapy of spinal cord injury.

PMID- 19159519
TI  - Self-excision of bilateral patellae treated by replantation: a report of one
      case.
AB  - Absence of patella may be caused by congenital factors, trauma and surgical
      operations (patellectomy, etc). Complete absence of bilateral patellae is rare in
      clinical case. We report a case of posttraumatic bilateral patella excision. To
      the best of our knowledge, absence of bilateral patellae caused by self
      mutilation has never been reported. Our patient and his family members were
      informed that the data concerning this case would be submitted for publication.

PMID- 19159520
TI  - [Issues related to standardization of immunohistochemistry].

PMID- 19159521
TI  - [Organizing annual conference to promote academic communication].

PMID- 19159522
TI  - [Standardization on establishment and application of tumor bank].

PMID- 19159523
TI  - [Recent advances on precursor lesions of female reproductive tract].

PMID- 19159524
TI  - [Annual conference of the pathology branch of Chinese Medical Societies in
      2008.].

PMID- 19159525
TI  - [The ninth national meeting on pathology, diagnosis and standardization of the
      related technologies.].

PMID- 19159526
TI  - [Primary ocular adnexal lymphoproliferative lesions: clinicopathologic features
      and genetic alterations].
AB  - OBJECTIVE: To investigate clinicopathological and genetic characteristics of
      primary ocular adnexal lymphoproliferative lesions. METHODS: Clinical,
      morphological and immunohistochemical features of 37 archival cases of primary
      ocular adnexal lymphoproliferative lesions were studied including 5 cases of
      reactive lymphoid hyperplasia and 32 lymphomas retrospectively. Classification of
      the lymphomas were made according to the WHO classification of tumors of
      haematopoietic and lymphoid tissues. All cases were studied by interphase
      fluorescence in situ hybridization (FISH) using dual color break apart probes of
      IgH, MALT1, bcl-6, c-Myc, bcl-2, CCND1, bcl-10, and FOXP1 for detection of
      chromosomal aberrations involving IgH, MALT1, bcl-6, c-Myc, bcl-2, cyclinD1, bcl
      10 and FOXP1 genes, respectively. FISH with IgH / bcl-2 dual color dual fusion
      probe was used for detection of t(14;18)(q32;q21)/IgH-bcl-2. CEP18 spectrum
      orange probe was used for detection of aneuploidy of the chromosome 18. RESULTS:
      Among 32 cases of lymphomas, 28 cases (87.5%) were extranodal marginal zone B
      cell lymphomas of mucosa associated lymphoid tissue (MALT lymphoma), 2 cases were
      follicular lymphoma (FL) and 2 cases diffuse large B cell lymphoma (DLBCL). Among
      the 28 cases of MALT lymphoma, chromosomal aberrations were found in 60.7%
      (17/28) by interphase FISH analysis. One case showed positive IgH break-apart
      signal with unknown partner. 16 cases showed three copies of different genes, of
      which, three copies of MALT1, bcl-6, and c-Myc were identified in 7 cases (25%),
      12 cases (43%), and 2 cases (8%) of MALT lymphomas, respectively. In addition, 5
      cases showed two genes including three copies of bcl-6 and MALT1 in 4 cases, and
      three copies of bcl-6 together with c-Myc in one case. Furthermore, all cases
      with three copies of MALT1 had trisomy 18. t(14;18)(q32;q21) was detected in both
      follicular lymphomas. Of the 2 DLBCL cases, one showed three copies of bcl-6
      together with trisomy 18 and the other one showed three copies of bcl-6 together
      with IgH and c-Myc rearrangements. Chromosomal aberration was not found in all 5
      cases of reactive lymphoid hyperplasia. CONCLUSIONS: The most common entity of
      primary ocular adnexal lymphomas is MALT lymphoma and FISH is helpful for their
      differential diagnosis and classification. Trisomy 18 and three copies of bcl-6
      are common chromosomal aberrations in primary ocular adnexal MALT lymphomas.

PMID- 19159527
TI  - [Relationship of cysteine-rich protein 61 and NF-kappaB expression with
      metastasis and prognosis of gastric carcinoma].
AB  - OBJECTIVE: To investigate the expression of cysteine-rich protein 61 (Cyr61) and
      NF-kappaB in gastric carcinoma and its correlation with the clinicopathologic
      features and survival time. METHODS: RT-PCR was used to validate and detect
      expression of Cyr61 mRNA in 53 gastric carcinoma specimens and 11 non-tumor
      gastric mucosa samples. Cyr61 and NF-kappaB protein levels expressed were
      detected using immunohistochemistry in 99 gastric carcinoma specimens and 25 non
      tumor gastric mucosa samples. RESULTS: RT-PCR demonstrated that expression of
      Cyr61 mRNA was higher in the primary carcinoma (84.6%, 22/26) and the metastatic
      foci (88.9%, 24/27) than in the non-tumor control samples (5/11; P < 0.05,
      respectively). Cyr61 gene mRNA expression levels were (2.76 +/- 5.50) x 10(-5),
      (14.61 +/- 20.64) x 10(-5), and (18.46 +/- 26.38) x 10(-5) by 2(-DeltaCt) in the
      control mucosa samples, primary carcinomas and metastatic tissues respectively.
      The level was higher in the primary carcinomas and metastatic tissues than that
      of the non-tumor gastric mucosa (P < 0.05, respectively); however, there was no
      significant difference between the metastatic tissues and the primary carcinomas
      (P > 0.05). Immunohistochemistry revealed that of the 99 cases, there was a high
      expression of Cyr61 and NF-kappaB protein, 56.6% (56/99) and 55.6% (55/99)
      respectively. There was correlation of Cyr61 and NF-kappaB protein expressions
      with the depth of tumor and vascular invasion, as well as the development of
      lymph node metastasis, and TNM staging (P < 0.05, respectively), besides, the
      expression of NF-kappaB also correlated with the tumor diameter (P < 0.05). Cyr61
      expression was positively correlated with NF-kappaB expression in gastric
      carcinoma (P < 0.05); the mean survival time in cases with a high expression
      level of Cyr61 and NF-kappaB protein was significantly shorter than those with a
      low expression level (P < 0.05). CONCLUSIONS: Expression of Cyr61 and NF-kappaB
      closely correlated with invasion and metastasis of gastric carcinoma. They may be
      considered as the biologic behavior indicators for gastric carcinoma.

PMID- 19159528
TI  - [SiRNA inhibition of E6AP expression in cervical cancer cells].
AB  - OBJECTIVE: To study the effect of RNA interference (RNAi) targeting E6AP on the
      proliferation and apoptosis of HeLa cells. METHODS: HeLa cells were cultured and
      divided into 3 groups: blank control group, cells transfected with nonsense siRNA
      (small interference RNA), and cells transfected with specific E6AP siRNA. The
      expressions of E6AP mRNA and protein were detected by RT-PCR and Western blot
      before and after the transfection respectively. Cell proliferation was determined
      by methylthiazolyl tetrazolium (MTT). The cell apoptosis index was assessed by
      flow cytometry. RESULTS: Upon treatment with E6AP siRNA for 24, 48 and 72 h, the
      expression level of E6AP mRNA decreased 33%, 72% and 70% than siRNA treated
      group. The protein expression levels in 48 h and 72 h E6AP siRNA groups decreased
      38%, 59% comparing with those of the nonsense siRNA treated group (P < 0.05). The
      proliferative capacity of cells transfectd with E6AP siRNA was significantly
      lower than blank control group (F = 101.38, P < 0.05) and siRNA treated group (F
      = 38.64, P < 0.05). The apoptosis index of HeLa cells treated with E6AP siRNA was
      significantly higher than that of the nonsense siRNA (F = 41.48, P < 0.05) and
      the blank control group (F = 86.36, P < 0.05). CONCLUSION: SiRNA targeting can
      effectively suppress the expression levels of E6AP mRNA, corresponding with a
      proliferation inhibition and an enhanced apoptosis of HeLa cells.

PMID- 19159529
TI  - [Effects of heparanase inhibition by RNA interference on proliferation,
      invasiveness and apoptosis of lung cancer cells].
AB  - OBJECTIVE: To investigate the effects of heparanase expression inhibition on the
      proliferation, invasiveness and apoptosis of human lung adenocarcinoma cell line
      A549 cells. METHODS: Recombinant eukaryotic expression plasmid pshRNA-Hpa
      targeting human heparanase gene was constructed. A549 cells were cultured in DMEM
      and transfected with pshRNA-Hpa. The expression of heparanase mRNA and protein
      were examined by RT-PCR and Western blot. The proliferation, invasiveness and
      apoptotic rates of A549 cells were determined by MTT method, matrigel invasion
      assays and flow cytometry respectively. RESULTS: The expression levels of
      heparanase mRNA and protein were down-regulated in A549 transfected with pshRNA
      Hpa. The number of cells penetrating matrigel and the proliferation ability of
      A549 cells transfected with pshRNA-Hpa were reduced significantly compared to the
      control cells. The apoptotic rate of A549 cells transfected with pshRNA-Hpa was
      12.53% +/- 0.34%, being significantly higher than that of the control cells (both
      P < 0.01). Western-blot showed that inhibition of heparanase expression led to
      reduced Akt phosphorylation. CONCLUSIONS: The recombinant plasmid pshRNA-Hpa
      effectively inhibited the expression of heparanase, thus suppressing the
      proliferation and invasion and inducing apoptosis of A549 cells. The effects may
      be due to the down-regulation of Akt phosphorylation level.

PMID- 19159530
TI  - [Short hairpin RNA silencing of vascular endothelial growth factor, telomerase
      reverse transcriptase, and Bcl-xl expression in human laryngeal squamous
      carcinoma xenografted in nude mice].
AB  - OBJECTIVE: To investigate the biological impact of pEGFP-shVEGF-shTERT-shBcl-xl
      expression in human laryngeal squamous carcinomas xenografted in nude mice and
      the related antitumor mechanism. METHODS: A recombinant plasmid vector containing
      3 different short hairpin RNA (shRNA) segments including pEGFP-shVEGF-shTERT
      shBcl-xl was constructed and directly injected into the grafted tumors of human
      laryngeal squamous carcinoma in nude mice. The mRNA and protein expressions were
      determined by real-time RT-PCR and Western blot respectively. Apoptosis was
      determined by TUNEL assay using a commercial kit. Intratumoral microvessel
      density (MVD) was assessed by immunhistochemistry. RESULTS: On the 14th days
      after the final treatment, mRNA and protein expression of VEGF, TERT, and Bcl-xl
      were markedly suppressed. The tumor sizes were significantly smaller than those
      in the other two group, with an overall tumor inhibition ratio of 91.2%. MVD
      counts in the pEGFP-shVEGF-shTERT-shBcl-xl treated group were significantly lower
      than those of the other two groups, along with increased apoptotic cells.
      CONCLUSIONS: The data showed that inhibition of VEGF, TERT, Bcl-xl expression by
      RNAi technique induces cellular apoptosis and suppresses the growth of laryngeal
      squamous carcinoma in vivo. VEGF, TERT and Bcl-xl may be involved in the
      development of laryngeal cancers. The findings suggest a synergistic tumor
      therapeutic effect through simultaneous inhibition of the three genes. Multi
      target RNA interference may provide a powerful strategy against human laryngeal
      cancers.

PMID- 19159531
TI  - [Hypoxia-inducible factor-1 alpha and its effects on tumor invasion and
      metastasis].

PMID- 19159532
TI  - [Handling and processing of radical prostatectomy specimens].

PMID- 19159533
TI  - [Abroad pathological standard reporting of breast carcinoma: an outline].

PMID- 19159534
TI  - [Tumour of the uterus].

PMID- 19159535
TI  - [Establish bank of tumor specimens and it's standardized management.].

PMID- 19159536
TI  - [Sclerosing angiomatoid nodular transformation of spleen: report of a case].

PMID- 19159537
TI  - [Multifocal eccrine angiomatous hamartoma: report of a case].

PMID- 19159538
TI  - [High-grade dysplasia arising in Peutz-Jeghers hamartomatous polyps: report of a
      case].

PMID- 19159539
TI  - [Dedifferentiated chondrosarcoma of rib: report of a case].

PMID- 19159540
TI  - [Perivascular epithelioid cell tumor of liver: report of a case].

PMID- 19159541
TI  - [Metastatic tumor in pituitary gland: report of a case].

PMID- 19159542
TI  - [The necessity for opening a specific clinical pathology from the aspect of
      advancement made in nervous pathology in China.].

PMID- 19159543
TI  - [How to do a successful job in the field of pathological consultation.].

PMID- 19159544
TI  - [Causes of errors in prenatal gene diagnosis and relevant countermeasures].

PMID- 19159545
TI  - [Pay more attention to the gene diagnosis and functional study to mitochondrial
      diseases].

PMID- 19159546
TI  - [Multiplex quantitative PCR detection for female carrier in an X-linked
      ichthyosis family].
AB  - OBJECTIVE: To analyze the pathogenic mutation of an X-linked ichthyosis (XLI)
      family, and identify the genetic diagnosis of three probable female carriers in
      this family. To evaluate the availability of different detect methods for steroid
      sulfatase (STS) gene mutation. METHODS: Peripheral blood samples were collected
      from the family, including the proband, proband's mother, younger sister, and
      younger female cousin, and 10 males and 10 females as controls. Ordinary PCR was
      used to detect whether there was STS gene deletion in the male proband. Then,
      multiplex quantitative fluorescent PCR (QF-PCR) was used to detect the STS gene
      in the proband and his 3 female family members. Fluorescence in situ
      hybridization (FISH) was used to authenticate the results of multiplex QF-PCR
      method. RESULTS: No amplified product of the exons 1-10 of STS gene deletion was
      detected by ordinary PCR in the proband. The proband's mother was diagnosed as a
      carrier, but his sister and cousin were diagnosed as normal females by multiplex
      QF-PCR. FISH confirmed the results of multiplex QF-PCR. CONCLUSION: Both
      multiplex QF-PCR and FISH are effective to detect the complete deletion mutation
      of STS gene and identify the female carrier, and multiplex QF-PCR is more
      convenient and automatic compared with FISH.

PMID- 19159547
TI  - [Identification of an ideal noninvasive method to detect A3243G gene mutation in
      MELAS syndrome].
AB  - OBJECTIVE: To identify a better non-invasive method to detect the carrier of
      mitochondrial A3243G mutation, a cause of mitochondrial encephalopathy-lactic
      acidosis-stroke like episode (MELAS) syndrome. METHODS: DNA was extracted from
      the peripheral blood, urine, hair follicle, and saliva of 25 MELAS syndrome
      patients carrying A3243G mutation and their mothers and other maternal relatives,
      33 persons in number, and the muscle tissues from 5 patients obtained by biopsy.
      A3243G mutation was detected by PCR-RFLP method, and the A3243G mutation ratio
      was identified by measuring the density of each band and calculation with the
      software AlphaEase 5.0. RESULTS: A3243G mutations were detected in all tissues of
      the 25 MELAS patients. The A3243G mutation ratio in urine was 62% +/- 9%,
      significantly higher than that in the blood [(36% +/- 10%), t = -11.13, P <
      0.01]. A3243G mutations were detected in at least one tissue of the 28 maternal
      relatives. The A3243G mutation rates in their urine samples was 33.0% (5.0% -
      70.4%), significantly higher than that in their blood samples [8.0% (0 - 33.3%),
      z = -4.197, P < 0.01]. There was no significant difference in A3243G mutation
      ratio among the samples of hair follicle, saliva, and blood. CONCLUSION: The
      A3243G mutation ratio in urine is significantly higher than those in blood
      samples of the patients and their maternal relatives. A noninvasive method,
      A3243G mutation ratio analysis of urine is superior to that in blood.

PMID- 19159548
TI  - [Mitochondrial DNA mutation analysis in 97 Chinese patients with mitochondrial
      cephalomyopathy].
AB  - OBJECTIVE: To investigate the characteristics of mitochondrial DNA mutations and
      genotype-phenotype correlations in mitochondrial encephalomyopathies. METHODS:
      Biopsy of skeletal muscle and collection of peripheral blood samples were
      conducted among 97 patients with mitochondrial encephalomyopathies. Southern
      blotting, PCR-RFLP and direct sequencing of PCR products were performed to search
      large scale deletions, and common and uncommon pathological point mutations in
      the muscle and/or blood mtDNA. RESULTS: Seventy-seven patients were identified to
      be with mitochondrial DNA mutations, including single large deletion (n = 21),
      multiple large-scale deletions (n = 4), A3243G point mutation (n = 43), A8344G
      point mutation (n = 6), T8993G mutation (n = 1), T8993C mutation (n = 1), and
      T3271C mutation (n = 1). Total mtDNA sequencing revealed 4 different novel point
      mutations in four unrelated patients with isolated mitochondrial myopathy.
      CONCLUSION: The type and frequency of mtDNA mutations in this series of Chinese
      mitochondrial encephalopathies are consistent with those reported abroad,
      Although there is some association between the genotype and phenotype,
      heterogeneity in phenotype and genotype is also a prominent feature seen in this
      series of patients, especially those with A3243G mutation.

PMID- 19159549
TI  - [Methylation-specific multiplex ligation-dependent probe amplification in
      diagnosis of Prader-Willi syndrome and Angelman syndrome].
AB  - OBJECTIVE: To verify the sensitivity and reliability of methylation-specific
      multiplex ligation-dependent probe amplification (MS-MLPA) and to develop a
      simple, accurate, reliability method of genetic diagnosis for AS and PWS.
      METHODS: Peripheral blood samples were collected from 4 suspected AS patients, 2
      suspected PWS patients, 2 normal persons, and 2 molecular biologically proven
      positive controls (1 AS patient and 1 PWS patient). DNA was extracted and
      purified. MS-MLPA was used to detect the methylation of the CpG dinucleotide and
      the copy number in the 15q-q13 region. The results of MS-MLPA were confirmed by
      MSP. RESULTS: Three cases with maternal deletion on 15q11-q13 region and one case
      with paternal uniparental disomy (UPD) or imprinting center defect in 15q11-q13
      region were found in the 4 suspected AS patients. One PWS case was found to be
      with paternal deletion in 15q11-q13 region and the other with paternal deletion
      in 15q11-q13 region or UPD or imprinting center defect in 15q11-q13 region.
      CONCLUSION: MS-MLPA is a simple, rapid, accurate, and reliable method of genetic
      test.

PMID- 19159550
TI  - [Molecular diagnosis of spinal muscular atrophy by multiplex ligation-dependent
      probe amplification].
AB  - OBJECTIVE: To investigate the effect of multiplex ligation-dependent probe
      amplification (MLPA) in molecular diagnosis of spinal muscular atrophy (SMA).
      METHODS: Peripheral blood samples were collected from 13 SMA patients, 31 parents
      of SMA patients, 50 healthy individuals without family history of SMA, and 10
      specimens of amniotic fluid from these families were collected too. Genomic DNA
      was analyzed by MLPA, conventional PCR-RFLP, and allele-specific PCR. RESULTS: In
      complete agreement with the results of conventional PCR-RFLP and allele-specific
      PCR, MLPA analysis showed that all of the 13 patients had homozygous deletion of
      the survival of motor neuron 1 (SMN1) gene, and there was significant difference
      between the SMA severity (type I to type III) and SMN2 copy number (P < 0.05). Of
      the 31 parents 29 (93.5%) had 1 copy of SMN1, 2 (6.5%) had 2 copies of SMN1. Of
      the 50 healthy individuals, 1 (2.0%) had 1 copy of SMN1, 48 (96.0%) had 2 copies
      of SMN1, and 1 (2.0%) had 3 copies. The SMN1 copy number of the parents was
      significantly higher than that of the healthy individuals (P < 0.01). Two of the
      10 fetuses had homozygous deletion of SMN1. CONCLUSION: The MLPA technique has
      proved to be an accurate and reliable tool for the molecular diagnosis of SMA,
      both in patients and in healthy carriers.

PMID- 19159551
TI  - [Valganciclovir for treatment of cytomegalovirus viremia in patients following
      allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To investigate the efficacy and safety of valganciclovir in treatment
      of cytomegalovirus viremia in patients following allogeneic hematopoietic stem
      cell transplantation (allo-HSCT). METHODS: Nineteen patients following allo-HSCT
      were diagnosed as with cytomegalovirus viremia with the CMV-DNA load of higher
      than 6.0 x 10(2) copies/ml confirmed by polymerase chain reaction (PCR) took
      orally valganciclovir at the dose of 900 mg bid for 14 days followed by 900 mg Qd
      for another 14 days. Since 4 weeks after the valganciclovir treatment PCR was
      conducted in the 6th, 8th, 12th, 16th, and 24th weeks later to detect the CMV-DNA
      level. RESULTS: CMV viremia was confirmed 40 days after HSCT on average with a
      median CMV-DNA load of 3.346 x 10(3) copies/ml. The total effective rate of
      valganciclovir was 94.7% (18/19). The CMV-DNA turned to negative in 7 d in 11
      cases with a negative transfer rate of 54.7%, and in 14 d in 16 cases with a
      negative transfer rate of 84.2%. The median CMV DNA load reduction was 0.75
      copies/ml and 0.084 log10 copies/ml/day. Severe adverse effects were not observed
      and CMV-related disease did not occur. CONCLUSION: Valganciclovir is an
      attractive and safe alternative for preemptive CMV viremia treatment in allo-HSCT
      recipients.

PMID- 19159552
TI  - [Values in preoperative assessment of occlusion and intra-operative guidance of
      64 row spiral CT in percutaneous coronary intervention for chronic coronary
      occlusion].
AB  - OBJECTIVE: To instigate the values of 64 row spiral CT in pre-operative
      assessment of the occlusion and intra-operative guidance in percutaneous coronary
      intervention for chronic total occlusion (CTO) in coronary heart disease.
      METHODS: Fifteen coronary disease patients planned to receive percutaneous
      coronary intervention underwent 64-row spiral CT-coronary angiography and
      coronary angiography (CAG). The diagnostic effects of these 2 techniques were
      compared. RESULTS: Seventeen CTO lesions were confirmed. MSCT succeeded to show
      the lengths of the 17 CTO lesions with a calcification identification rate of
      76.4%, significantly higher than that of the CAG (41.5%). By cross-section
      examination, MSCT succeeded to detect the occlusion degree of the calcified
      lesions, and showed that 3 CTO lesions were occluded at a rate < 50%, and 10
      lesions at a rate > or = 50%. Twelve complete occlusion lesions in 11 patients
      underwent PCT, success was seen in 6 of which and failure in the other 6.
      Univariate analysis showed that the length of lesion, branching at the proximal
      site, formation of bridging lateral branch, form of occlusion end, and
      calcification were all not significantly related to the success or failure of
      intervention. The percentage of the calcification area > or = 50% in the
      intervention failure group was 83.3%, significantly higher than that in the
      intervention success group (16.7%, P = 0.05). 3-D images of coronary artery could
      be obtained by MSCT to show all the complete occlusive lesions. CONCLUSION: 64
      MSCT demonstrates a remarkable ability to identify silicified lesions, can re
      establish 3-D images of coronary artery, and effectively guide the intervention
      therapy.

PMID- 19159553
TI  - [Expression of caveolin-1 gene in hepatitis B-related hepatocellular carcinoma
      and the clinical significance thereof].
AB  - OBJECTIVE: To study the correlation between the expression of caveolin-1 in
      hepatitis B-related hepatocellular carcinoma (HCC) and the relationship thereof
      with the invasive and metastatic ability of HCC. METHODS: Real-time PCR and
      immunohistochemistry were used to detect the expression of caveolin-1 in 123
      specimens of HCC tissues obtained during operation. Human HCC cells of the lines
      MHCC-97L and MHCC-97H were cultured, and Western-blotting was used to detect the
      caveolin-1 expression in these cells. RESULTS: The expression level of caveolin-1
      in the HCC tissues was significantly lower than that of the adjacent noncancerous
      tissues (P = 0.026). The caveolin-1 mRNA expression in the HBV-related HCC cells
      was negatively correlated with the tumor size, expression of AFP, major venous
      invasion, being single or multiple, pTNM staging, and HBx expression level,
      factors closed to the prognosis of HCC. The caveolin-1 protein expression of the
      MHCC-97H cells was significantly lower than that of the MHCC-97L cells.
      CONCLUSION: Caveolin-1 expression is associated with the invasive and metastatic
      ability of HCC, low expression of caveolin-1 shows poor prognosis of HCC, and
      caveolin-1 is probably down-regulated by HBx protein.

PMID- 19159554
TI  - [Clinical analysis of small cell neuroendocrine carcinoma of the head and neck].
AB  - OBJECTIVE: To seek a best therapeutic protocol for small cell neuroendocrine
      carcinoma of head and neck. METHODS: The clinical data of 34 patients with small
      cell neuroendocrine carcinoma of head and neck, 21 males and 13 females, aged 53
      (17 - 71), were retrospectively analyzed. The therapeutic protocols that had been
      used for the patients included surgery alone (in 5 patients), radiotherapy alone
      (in 7 patients), combined therapy with surgery and radiotherapy (in 7 patients),
      combined therapy with surgery and chemotherapy (for 3 patients), combined therapy
      with radiotherapy and chemotherapy (for 10 patients), and combined therapy with
      surgery, radiotherapy and chemotherapy (for 2 patients). The follow-up ended on
      August 1 2007. RESULTS: The prognosis of the patient with small cell
      neuroendocrine carcinoma of skin was the best. Local recurrence occurred in 7
      patients, of which 2 underwent surgery alone, 2 combined therapy with surgery and
      radiotherapy, 1 combined therapy with surgery and chemotherapy, and 2 combined
      therapy with radiotherapy and chemotherapy. Recurrence in neck occurred in 1
      patient that had undergone combined therapy with surgery and radiotherapy. Neck
      lymph node metastasis was found in 4 patients of whom 2 had undergone surgery
      alone, 1 had undergone combined therapy with surgery and chemotherapy, and 1
      combined therapy with radiotherapy and chemotherapy. Distant metastasis was found
      in 11 patients of whom 2 had undergone surgery alone, 2 radiotherapy alone, 3
      combined therapy with surgery and radiotherapy, and 3 combined therapy with
      radiotherapy and chemotherapy. The median survival time was 24 months, and the
      overall 3-year and 5-year cumulative survival rates were 65.37% and 35.95%
      respectively. CONCLUSION: The prognosis of the patient with small cell
      neuroendocrine carcinoma of head and neck was poor. Small cell neuroendocrine
      carcinoma cases with the lesions at different sites differ in prognosis and
      needed different therapeutic fashions. Combined therapy with radiotherapy and
      chemotherapy is recommended for small cell neuroendocrine carcinoma of head and
      neck, and surgery serves as a salvage therapeutic measure.

PMID- 19159555
TI  - [Expression of cyclooxygenase-2 and urokinase plasminogen activator in gastric
      carcinoma and the clinical significance thereof].
AB  - OBJECTIVE: To investigate expression of cyclooxygenase-2 (COX-2) and urokinase
      plasminogen activator (uPA) in gastric carcinoma and the clinical significance
      thereof. METHODS: Strepavidin-peroxidase method was used to detect the expression
      of COX-2 and uPA in 192 specimens of gastric carcinoma, 56 specimens of
      paracancer tissues obtained during operation. Immunohistochemical double staining
      was used to detect the microvessel density (MVD) and microlymphatic density
      (MLD). Thirty specimens of normal gastric mucosa obtained during gastroscopy were
      used as controls. RESULTS: The positive rates of COX-2 in the gastric carcinoma
      and paracancer tissues were 67.7% and 62.5% respectively, both significantly
      higher than that of the control group (40.0%, both P < 0.05). The positive
      expression of COX-2 in gastric carcinoma was significantly related with the depth
      of invasion and MVD (both P < 0.05). The positive rates of uPA in the gastric
      carcinoma, paracancer tissue were 78.1% and 44.6% respectively, both
      significantly higher than that of the control tissues (6.7%, both P < 0.01) and
      there was a significant difference in the positive rates of uPA between the first
      2 groups too (P < 0.01). The positive expression of uPA in gastric carcinoma was
      significantly related with lymph node metastasis, depth of invasion, Lauren
      typing, differentiation, MVD, and MLD (P < 0.05, P < 0.01). COX-2 expression was
      positively linked with uPA expression (r = 0.167, P = 0.021). The survival time
      of the uPA positive group was (38 +/- 4) months, significantly shorter than that
      of the negative group [(54 +/- 6) months, P < 0.05]. The survival time of the
      group positive in both COX-2 and uPA was (27 +/- 3) months, significantly shorter
      than that of the single positive or double negative groups [both (58 +/- 4)
      months, both P < 0.01). CONCLUSION: COX-2 and uPA are highly expressed in gastric
      carcinoma. COX-2 expression is positively linked with uPA expression. COX-2 and
      uPA in the gastric carcinoma participate in the development of gastric cancer in
      the early process. uPA is significantly related with the survival time.

PMID- 19159556
TI  - [Depression before and after operation in patients undergoing coronary artery
      bypass grafting and the effect thereof on quality of life].
AB  - OBJECTIVE: To investigate the presence and severity of depression before and
      after operation in patients undergoing coronary artery bypass grafting (CABG) and
      the effect thereof on the quality of life. METHODS: A validated Chinese version
      of Beck Depression Inventory (BDI) was used in 138 CABG patients that were
      divided into 2 groups according the fact if depression was present. 1 week before
      and 1, 3, and 6 months after operation, and SF-36 scale was used to evaluate the
      quality of life (QOL) one week before operation and 1 and 6 months after
      operation. RESULTS: Depressive disorders occurred in 42.7% of the patients
      preoperatively and in 23.1% of the patients 6 months after the operation. There
      were no significant differences in all the dimensions of the SF-36 scale before
      operation between the depression and non-depression groups. All the scores of the
      36-F dimensions were improved 1 and 6 months after the operation. However, the SF
      36 social functioning (SF), mental health (MH), role emotional (RE), and bodily
      pain (BP) subscale scores 6 months after operation of the depression group were
      all lower than those in the non-depressive groups (all P < 0.05). CONCLUSION:
      Depression symptoms at different degrees exist before CABG and can be improved
      post-operatively. The improvement of QOL of the depressive patients after
      operation is not so marked compared to the non-depressive patients, especially in
      SF, MH, RE, and BP dimensions.

PMID- 19159557
TI  - [Effects of early insulin therapy on nuclear factor kappaB pathway in skeletal
      muscle of diabetes: experiment with rats].
AB  - OBJECTIVE: To investigate the effect of early insulin therapy on the nuclear
      factor kappaB (NF-kappaB) pathway and inflammatory cytokine responses in skeletal
      muscle in type 2 diabetes mellitus (DM). METHODS: SD rats underwent
      intraperitoneal injection of streptozotocin to establish DM models and then
      divided into 5 groups: early un-treated group, early gliclazide treated group
      (receiving gliclazide since the third day after blood glucose increase for 3
      weeks for 3 weeks), early insulin treated group (receiving insulin since the
      third day after blood glucose increase for 3 weeks for 3 weeks), late un-treated
      group, and late insulin treated group (receiving insulin since the fourth week
      after blood glucose increase for 3 weeks). By the end of treatment the rats were
      killed. Homogenate of skeletal muscle was made. The NF-kappaB P65 DNA binding was
      assayed by ELISA-based assay kit. Real time PCR was used to detect the mRNA
      expression levels of the gene of the cytokines: glucose transporter 4 (Glut4),
      inhibitor kappaB (IkappaBalpha), IL-1beta, IL-6, and tumor necrosis factor (TNF)
      alpha. And Glut4 and IkappaBalpha protein expression levels were assayed by
      Western blotting. RESULTS: The Glut4 mRNA level in the skeletal muscle of the
      untreated DM rats decreased by 59% and the Glut4 protein level in the muscle cell
      membrane decreased by 69%. Insulin treatment and gliclazide treatment increased
      the Glut4 mRNA expression by 17% and 13% respectively, increased the Glut4
      protein expression in cell membrane by 23% and 10% respectively, and decreased
      the Glut4 protein expression in the cytoplasm. In the DM rats the IkappaBalpha
      protein expression in the skeletal muscle was significantly lower (P < 0.05) and
      the NF-kappaB P65 DNA binding activity increased, and TNF-alpha, IL-1B, and IL-6
      expression levels were up-regulated in comparison with the normal control group.
      Early treatment of insulin and gliclazide increased the IkappaBalpha protein
      expression, decreased the NF-kappaB P65 DNA binding activity and the TNF-alpha
      expression in the skeletal muscle. CONCLUSION: Early insulin treatment inhibits
      the NFkappaB activity and inflammatory cytokine responses in skeletal muscle that
      are involved in the amelioration of insulin resistance in type 2 DM. Such results
      may be due to indirect antiinflammatory effects of insulin relieving
      glucotoxicity and lipotoxicity in peripheral tissues.

PMID- 19159558
TI  - [A highly sensitive enzyme-linked immunosorbent assay for measurement of leptin
      secretion in human adipocytes].
AB  - OBJECTIVE: To establish a highly sensitive and specific ELISA method for
      measurement of leptin and further to study the secretion of leptin during human
      preadipocytes differentiation and effects of troglitazone. METHODS: Rabbits
      Balb/c mice were immunized by recombinant human leptin and Balb/c mice were
      immunized by human leptin so as to produce rabbit anti-human leptin polyclonal
      antibodies (PAb) and mouse anti-human leptin monoclonal antibodies (MAb).
      Combination of the PAb as coating antibody, with a carefully paired biotinylated
      MAb as detector, and the avidin-horseradish peroxidase as the amplifier of
      detecting signals, a sandwich method, biotin-avidin ELISA (BA-ELISA) was
      established. Human omental preadipocytes were cultured, introduced to
      differentiate, and treated with 10 micromol/L troglitazone; the leptin secretion
      in the supernatant was detected by BA-ELISA. Peripheral blood samples were
      collected from 114 healthy persons and the serum leptin was detected by BA-ELISA.
      RESULTS: The sensitivity of BA-ELISA was 0.03 ng/ml with a working range of 0.05 
      5 ng/ml and a exogenous leptin recovery rate of 97.8%, and the intra- and
      interassay coefficients of variation (CVs) were less than 7.4% and 9.3%
      respectively. The assay detected only a single free leptin peak in gel
      chromatographic fractions from the mixed human sera or adipocytes culture media.
      The leptin secretion level detected by BA-ELISA showed that the leptin secretion
      of the preadipocytes increased strongly when the cells differentiated into mature
      adipocytes. The peak leptin secretion level of the troglitazone treated group was
      2 times as that of the control group. The leptin concentration of women was than
      7.6 ng/ml, significantly higher than that of the men (3.2 ng/ml, P < 0.001), and
      the serum leptin level was significantly correlated with body mass index both for
      men (r = 0.67, P < 0.001) and for women (r = 0.61, P < 0.001). CONCLUSION: A
      highly sensitive BA-ELISA specific for free leptin has been developed that is
      especially suited for the accurate measurement of the rather low leptin levels of
      clinical blood specimens and for basic research use.

PMID- 19159559
TI  - [Differential analysis of protein profiles of vesicular phase and micellar phase
      of gallbladder bile from cholesterol gallstone patients].
AB  - OBJECTIVE: To identify the proteins which play key roles during the formation of
      cholesterol gallstone, differential analysis was carried out that the proteome of
      vesicular phase and micellar phase of gallbladder bile from cholesterol gallstone
      patients. METHODS: Vesicular and micellar phases were isolated by the density
      gradient ultracentrifugation method. Total proteins from the two phases were
      extracted, and the protein expressional profiles were established by two
      dimensional electrophoresis respectively. The differentially expressed protein
      spots analyzed by ImageMaster two-dimensional electrophoresis analysis software
      were identified with matrix-assisted laser desorption ionization time-of-flight
      mass spectrometry (MALDI-TOF-MS). RESULTS: The concentrations of proteins from
      vesicular phase and micellar phase of gallbladder bile from cholesterol gallstone
      patients were (1.5358 +/- 0.0682) mg/ml and (7.1222 +/- 0.2022) mg/ml (P < 0.01)
      respectively. The average matched protein spots were 120 +/- 24 and 198 +/- 37 in
      the two groups respectively. There were 72 +/- 16 matched spots in the two
      representative gels maps and the matched rate was 45.30%. Eight differentially
      expressed protein spots were identified from the two cholesterol-carrier phases.
      Among them, 6 were up-regulated with 2 down-regulated in vesicular phase compared
      with micellar phase. The abundance differentiation of RBP and HSA was confirmed
      by immunoblotting. CONCLUSIONS: The differential protein profiles of vesicular
      phase and micellar phase of gallbladder bile from cholesterol gallstone patients
      were established and 8 differential protein spots were identified successfully.
      The data may be a basis for further screening the key regulators of formation of
      cholesterol gallstone.

PMID- 19159560
TI  - [Impedance of cochlear implant electrode array in scalae tympani].
AB  - OBJECTIVE: To study the relationship between the impedance of paired cochlear
      implant electrodes and their position in scalae tympani as well as the
      relationship between the impedance and the current frequency. METHODS: REZ-1
      electrodes were implanted in 6 fresh human adult temporal bone specimens.
      Alternating electrical source was used. A 1 Kohm resistance was in series with
      the paired electrodes. The voltages of the resistance and the sum voltages of
      both the paired electrodes and the resistance were recorded. Thus, the impedances
      of paired electrodes could be calculated. The impedances of neighboring paired
      electrodes and paired electrodes separated by one electrode were calculated. The
      frequencies of signals were 2 Hz, 10 Hz, 100 Hz, 1 KHz, and 10 KHz respectively.
      RESULTS: The impedances of neighboring electrodes increased, as the electrodes
      were closer to the apical turn of the cochlea (liner regression, F = 198.97, P <
      0.001). The impedances of paired electrodes separated by one electrode increased,
      as the electrodes were closer to the apical turn of the cochlea (liner
      regression, F = 126.35, P < 0.001). The impedance decreased when the frequency
      increased. CONCLUSIONS: The impedances of neighboring electrodes increase, as the
      electrodes are closer to the apical turn of the cochlea. The impedances of
      neighboring paired electrodes increase, as they are closer to the apical turn in
      the scalae tympani. The impedances of paired electrodes that are separated by one
      electrode increase, as they are closer to the apical turn in the scalae tympani.
      The impedance decreases when the frequency increases.

PMID- 19159561
TI  - [Diagnostic values of double-balloon enteroscopy and abdominal computed
      tomography in small bowel disease].
AB  - OBJECTIVE: To evaluate the diagnostic values of double-balloon enteroscopy (DBE)
      and abdominal computed tomography (CT) in small bowel disease. METHODS: Seventy
      eight DBE procedures were carried out in 70 patients, 40 males and 30 females;
      aged 47.7 (16 - 83) with suspected small bowel disease, all of whom received
      gastroscopy, colonoscopy, and abdominal CT examination at the same time. The
      diagnostic value of DBE was compared with that of CT. RESULTS: Seventeen kinds of
      small bowel lesions were detected, mainly including Crohn's disease,
      adenocarcinoma, gastrointestinal stroma tumor, vascular deformity, lymphoma,
      diverticulum, and polyp. There were no complications and all procedures were
      tolerated well. The mean duration of procedure was 110 min (30 - 240 min).
      Nineteen patients received surgical intervention. The diagnostic yield rate of
      DBE was 57.1% (40/70), significantly higher than that of CT (31.4%, 22/70, P <
      0.01). The positive diagnosis rate of DBE combined with CT was 62.9% (44/70), not
      significant different from that of the DBE alone (P > 0.05). CONCLUSION: DBE
      shows a significantly higher diagnostic yield than CT in patients with suspected
      small bowel disease, and thus should be selected for the initial diagnosis. DBE
      Combined with CT did not increase the diagnostic yield. However, CT not only
      provides direction of intubation for DBE, but also clearly depicts the small
      bowel wall and extraenteric alterations. DBE and CT compliment each other in
      examining the patients with suspected small bowel disease.

PMID- 19159565
TI  - [Attention to the monitoring of high-risk populations for pulmonary
      tuberculosis].

PMID- 19159567
TI  - [Immunoglobulin domain and mucin domain-1 in helper T lymphocytes in allergic
      rhinitis].
AB  - OBJECTIVE: To investigate the significance of T cell immunoglobulin domain and
      mucin domain-1 (TIM-1) expression in helper T lymphocyte in allergic rhinitis
      (AR) patients. METHODS: Peripheral blood samples were collected from 20 AR
      patients, 9 males and 11 females, aged 31.4 (20-54), and 20 healthy persons, 12
      males and 8 females, aged 38, 6 (18-60). Peripheral blood mononuclear cells
      (PBMNs) were isolated and magnetic cell sorting technique was used to purify the
      CD4+ T cells and CD4 + CD45RA + T cells. Immunofluorescence staining and flow
      cytometry were used to detect the percentage of CD4 + CD45RA + T cells positive
      in TIM-1, a helper T lymphocyte marker. Phytohemagglutinin (PHA) was added into
      the culture media to stimulate the TIM-1 positive helper T lymphocytes. Dendritic
      cells (DCs) thus induced and differentiated were conditioned by standardized
      allergen from dust mite (Dermatophagoides pteronyssinus) or lipopolysaccharide
      (LPS), and then co-cultured with CD4 T cells. The percentage of TIM-1 positive
      CD4 + CD45RA + T cells was counted. ELISA was used to detect the IL-4 and
      interferon (IFN)-gamma levels in the supernatants of the culture media of the
      dust mite and LPS groups. RESULTS: The percentage of TIM-1 positive CD4+ T cells
      of the AR patients was (9.48 +/- 1.51)%, significantly higher than that of the
      healthy controls [(3.12 +/- 0.32)%, P < 0.05], and the percentage of TIM-1
      positive CD4 + T cells after PHA stimulation of the AR patients was (47.05 +/-
      4.35)%, significantly higher than that of the healthy controls [(29.92 +/-
      3.36)%, P < 0.05]. The percentage of TIM-1 positive CD4 + CD45RA + T cells of the
      AR patients was (26.34 +/- 4.0)%, significantly higher than that of the healthy
      controls [(18.4 +/- 8.1)%, P < 0.05], and the percentage of TIM-1 positive CD4 +
      CD45RA + T cells after PHA stimulation of the AR patients was (65.3 +/- 7.4)%,
      significantly higher than that of the healthy controls [(36.3 +/- 6.8)%, P <
      0.05]. The percentage of TIM-1 positive CD4 + CD45RA + T cells co-cultured with
      the DCs conditioned by dust mite of the AR patients was (10.81 +/- 1.48)%,
      significantly higher than that of the LPS group [(6.08 +/- 1.45)%] and the blank
      control group [(1.56 +/- 2.30)%, both P < 0.05]. The IL-4 level of the DCs
      conditioned by dust mite allergen was (74.61 +/- 13.82) pg/ml, significantly
      higher than those of the LPS group and blank control group [(28.57 +/- 3.36) and
      (1.40 +/- 0.99) ng/ml respectively, both P < 0.05]. The IFN-gamma level of the
      DCs conditioned by dust mite allergen was (25.31 +/- 7.23) pg/ml, significantly
      lower than that of the LPS group [(163.41 +/- 82.37) pg/ml, P < 0.05], however,
      significantly higher than that of the blank control group [(1.58 +/- 0.53) pg/ml,
      P < 0.05]. CONCLUSION: The percentage of TIM-1 positive helper T lymphocytes of
      the AR patients are abnormally high. After stimulation of allergen The DCs
      increase the number of TIM-1 expressing naive Th cells and promote them to
      differentiate into Th2 cells. Promoting naive Th cells to differentiate into Th2
      cells, TIM-1 expression induces Th2 cytokine-based immune responses.

PMID- 19159566
TI  - [Effects of two treatment regimens for drug-resistant tuberculosis in
      tuberculosis control project areas: a comparative study].
AB  - OBJECTIVES: To search for an ideal therapeutic regimen for multidrug resistant
      tuberculosis conforming to the situation of China. METHODS: One hundred and fifty
      four patients with rifampin-resistant tuberculosis, 114 multi-drug resistant (MDR
      TB) and 40 resistant to other drugs, in Heilongjiang, Zhejiang, and Shenzhen, 107
      males and 47 females, aged 39 (19-77), were randomly divided into 2 groups: 85
      patients in the group of drug-resistant regimen, 3RFT AM Ofx Pto PAS-INH/5RFT Ofx
      Pto PAS-INH regimen, including rifapentine (RFT), amikacin (Am), ofloxacin (Ofx),
      protionamide (Pto), para-aminosalicylic acid-isoniazid (PAS-INH) for 3 months and
      then RFT, Ofx, Pto, and PAS-INH for 5 months, and 69 in the retreatment regimen
      group undergoing 3 H3R3Z3E3S3/5 H3R3E3, including isoniazid (H), rifampin (R),
      pyrazinamide (Z), ethambutol (E), and streptomycin (S) for 3 months and then H,
      R, and E for 5 months. Sputum smear was checked and the sputum smear conversion
      rate was calculated as an effective treatment indicator 3, 6, and 8 months later.
      RESULTS: One hundred and fourteen of the 154 patients were treated for a good 8
      months. The sputum smear conversion rate 8 months after treatment of the drug
      resistant regimen group was 65.9% (56/85), significantly higher than that of the
      retreatment regimen group [40.6% (28/69), chi2 = 9.834, P = 0.002]. Eighty-five
      of the 114 MDR-TB patients had been treated for a good 8 months with a sputum
      smear conversion rate of 61.8% (42/68), significantly higher than that of the
      retreatment regimen group [39.1% (18/46), chi2 = 5.638, P = 0.018]. Sputum smear
      conversion at the end of the 8th month was related to age, course of disease,
      therapeutic regimen, and the type of drug-resistance (all P < 0.05). The side
      effect rate of the drug-resistant regimen group was 23.9% (17/71), higher than
      that of the retreatment regimen group [18.6% (8/43)], but not significantly (chi2
      = 0.446, P = 0.504). CONCLUSION: The drug-resistant regimen recommended above is
      more effective than the retreatment regimen and should be considered in the areas
      where the WHO guideline fails to be followed or drug sensitivity test (DST)
      cannot be conducted and adjusted according to the results of DST and treatment.

PMID- 19159568
TI  - [Expression of estrogen receptor, progesterone receptor, and human epithelial
      growth factor receptor 2 in breast cancer and the significance thereof: analysis
      of 910 cases].
AB  - OBJECTIVE: To investigate the expression of estrogen receptor (ER), progesterone
      receptor (PR), and human epithelial growth factor receptor 2 (HER2) in breast
      cancer, and to explore their correlation with the age of patient, and size,
      clinic stage, and lymph node metastasis of the tumor. METHODS: The data of 910
      breast cancer, 89.4% of invasive ductal carcinoma, 1.7% of invasive lobular
      carcinoma, 44 cases 5% of ductal carcinoma in situ, and 4.9% of other pathologic
      types, 29.9% being less than 2 cm, 45.6% being 2-5 cm, and 24.5% bigger than 5 cm
      in size, 54.2% without metastasis in lymph node, 25.5% with metastasis in 1-3
      lymph nodes, and 20.3% with metastasis in more than 3 lymph nodes respectively,
      were analyzed retrospectively. Immunohistochemistry was used to detect the
      expression of ER, PR, and HER2. RESULTS: The ER negative expression rate was
      33.0%, and PR negative expression rate was 27.4%, and HER2 overexpression rate
      was 20.3%. The possibility of lymph node metastasis decreased along with the
      increase of age (P < 0.001). Tumor size was negatively correlated with the
      expression of ER and PR (both P < 0.001), and positively correlated with the
      expression of HER2 (P < 0.001). There was no significant difference between the
      situation of lymph node metastasis and the expression of ER, PR and HER2 in
      primary tumors. CONCLUSION: As good prognostic markers of breast invasive ductal
      cancer, ER and PR are negatively correlated with the HER2 expression, as a worse
      prognostic marker. ER/PR positive or HER2 negative tumors are morel likely to be
      diagnosed at earlier stages.

PMID- 19159569
TI  - [Elimination of leukemic CD34+ progenitor cells by using cytotoxic T lymphocytes
      specifically targeting WT1-derived peptide: an experimental study in vitro].
AB  - OBJECTIVE: To investigate the effects of targeting elimination of the leukemic
      CD34+ progenitor cells by using cytotoxic T lymphocytes (CTLs) specifically
      against Wilms tumor gene (WT1)-derived peptide. METHODS: A 9-mer WT1 peptide
      (CMTWNQMNL) containing HLA-A * 0201-binding anchor motifs was synthesized. The
      suspended cells were collected from the culture of the peripheral blood
      mononuclear cells and divided into 2 groups: Group D (pure T cells) and Group C
      (IL2 + T cells). The dendritic cells (DCs) generated from the peripheral blood
      mononuclear cells of an HLA-A* 0201-positive healthy donor were repeatedly loaded
      with WT1 peptide so as to elicit cytotoxic T cells (CTLs) specifically for WT1
      peptide, and restricted by HLA-A * 0201 (Group A). The specific lysis effects of
      WT1 peptide specific CTLs upon leukemic bone marrow CD34+ progenitor cells
      positively expressing WT1 (3 being HLA-A * 0201(+) and 3 being HLA-A*0201(-)),
      peripheral blood CD34+ cells from healthy persons (2 being HLA-A * 0201(+) and 1
      being HLA-A * 0201(-)), and leukemia cells of the lines of NB4 (HLA-A *
      0201(+)/WT1(+)), U937 (HLA-A * 0201(+)/WT1(-)), and K562 (HLA-A * 0201(-)/WT1(+))
      were measured by methyl thiazolyl tetrazolium (MTT) chromatometry assay. The
      colony-forming unit-granulocyte macrophage (CFU-GM) forming capability of the
      leukemic bone marrow CD34+ progenitor cells and peripheral blood CD34+ cells from
      healthy persons treated with WT1 peptide specific CTLs were also determined by
      methylcellulose medium colony-forming unit assay. The CTLs elicited by DCs
      without WT1 peptide loading(Group B)and T cells cultured with IL-2 (Group C) were
      taken as controls. RESULTS: The CTLs specific for WT1 peptide and restricted by
      HLA-A * 0201 (Group A) exerted a specific lysis upon the 3 cases with HLA-A *
      0201(+)/WT1(+) leukemic bone marrow CD34+ progenitor cells and NB4 leukemia
      cells, the specific lysis levels were 55.3% +/- 2.8%, 67.1% +/- 3.2%, 49.4% +/-
      3.8% and 55.0% +/- 3.7% respectively, all significantly higher than those upon
      the 3 cases with HLA-A * 0201(-)/WT1(+) leukemic bone marrow CD34+ progenitor
      cells, normal healthy peripheral blood CD34+ cells of the healthy persons, and
      leukemia cell of the lines K562 and U937 (the specific lysis levels were all <
      20%). The specific lysis level of Group A CTLs was significantly higher than
      those of Group B and Group C CTLs (both P < 0.01). The relative colony formation
      rates of WT1-CTLs in Group A upon the 2 cases with HLA-A * 0201(+)/WT1(+)
      leukemic CD34+ progenitor cells were 17.8% +/- 4.0% and 20.8% +/- 3.41%
      respectively, both significantly lower than those of the none WT1-CTLs in Group B
      (88.9% +/- 3.4% and 91.8% +/- 5.7% respectively, both P < 0.01). There was no
      significant difference in the relative colony formation rate upon HLA-A *
      0201(+)/WT1(-) leukemic bone marrow CD34+ progenitor cells and the HLA-A * 0201(
      )/WT1(-) or HLA-A * 0201(+)/WT1(-) normal peripheral blood CD34+ progenitor cells
      between the CTLs of Groups A and B. CONCLUSIONS: The CTLs specific for WT1 and
      restricted by HLA-A * 0201 can exert specific lysis upon leukemic CD34+
      progenitor cells highly expressing WT1 gene, and can inhibit the CFU-GM colony
      formation of such leukemic CD34+ progenitor cells. The product of expression of
      WT1 gene may be used as a target in the leukemic CD34+ cells.

PMID- 19159570
TI  - [Effects of donor age and gender on early acute rejection episode in living
      related donor kidney transplantation].
AB  - OBJECTIVE: To identify the risk factors of acute rejection events after living
      related donor renal transplant. METHODS: Renal transplantation was performed on
      117 patients, 85 males and 32 females, aged 9-57, with the kidneys from 117
      donors, 63 males and 54 females, aged (47 +/- 6) (20-65). The cumulative
      incidence of acute rejection events was respectively evaluated by Kaplan-Meier
      product-limit method and log-rank test. Cox's proportional hazards model was used
      to determine the risk factors for acute rejection events. RESULTS: Follow-up was
      conducted for 16 (3-44) months. The acute rejection rates 2 and 6 weeks after
      transplantation of the group with the donor aged > or = 50 were 13.0% and 19.5%
      respectively, both significantly higher than those of the group with the donor
      aged < 50 (2.8% and 8.5% respectively, P = 0.010). The risk of being female for
      acute rejection was 2.731 times as that of being male (95% CI: 1.018-7.326, P =
      0.046), and the risk of donor aged > or = 50 for acute rejection was 1.054 times
      as that of the donors aged < 50 (95% CI: 1.004-1.107, P = 0.020). CONCLUSION: The
      requirement for selecting elder living kidney donor should be stiff. Injury to
      the kidney should be avoided when the kidney of an elder donor is removed and
      transplanted. Early administration of sufficient immunosuppressive agents is
      necessary to the recipients of the kidney from an old or female living donor.

PMID- 19159571
TI  - [BRAF mutation in colorectal serrated lesions].
AB  - OBJECTIVE: To investigate the viral oncogene homolog B1 (BRAF) mutation frequency
      in serrated colorectal adenocarcinoma (Sca), and to verify the existence of a new
      serrated pathway indirectly. METHODS: 75 paraffin-embedded tissue samples,
      including 15 cases of Sca, 20 cases of traditional serrated adenoma (TSA), 20
      cases of non-serrated adenocarcinoma (NS-ca), and 20 cases of villous adenoma,
      were reviewed. Nest-PCR was used to amplify the exon 15 fragment of BRAF gene.
      RFLP assay was used to detect the BRAF V600E mutation. The positive samples were
      verified by direct sequencing. RESULTS: Four of the 11 successfully amplified Sca
      specimens (4/11, 36.4%), and 4 of the 15 TSA samples (4/15, 26.7%) harbored BRAF
      V600E mutation. However, no BRAF V600E mutation was found in the 14 NS-ca samples
      and the 11 villous adenoma specimens. The BRAF V600E mutation frequencies of the
      villous adenoma group and NS-ca group were significantly lower than those of the
      TSA group and Sca group (P = 0.0084); however, there was no statistical
      difference in the frequency of BRAF V600E mutation between the Sca and TSA groups
      (P > 0.05). CONCLUSION: BRAF V600E mutation frequency is significantly higher in
      the Sca and TSA patients than in the NS-ca and villous adenoma patients. There is
      actually a new serrated neoplasia pathway different from the traditional adenoma
      carcinoma carcinogenesis pathway.

PMID- 19159572
TI  - [Signal transduction pathway of colonic Toll-like receptor 4 in patients with
      irritable bowel syndrome].
AB  - OBJECTIVE: To study the expression of TLR4, myeloid differential protein 2 (MD
      2), and nuclear factor (NF)-kappa B in the colonic mucosa with irritable bowel
      syndrome (IBS) in patients and to explore the role of TLR4 in the pathogenesis of
      IBS and TLR4 signal transduction pathway. METHODS: Immunohistochemistry was used
      to detect the expression of TLR4, MD-2, and NF-kappaB in the colon mucosa
      specimens of 30 patients with diarrhea-predominant irritable bowel syndrome (IBS
      D) and 12 healthy volunteers obtained by colonoscopy. RESULTS: The A value of
      TLR4 in the IBS specimens was (0.40 +/- 0.10), significantly higher than that of
      the specimens from the controls [(0.30 +/- 0.05), P = 0.001]. MD-2 expression was
      not seen in the intestinal epithelial cells (IECs) of 10 healthy controls and was
      lowly expressed in the sigmoid mucosa of 2 of the 12 healthy controls; and was
      lowly expressed in 4 of the IBS patients and not expressed in 26 of the 30 IBS
      patients. The mean number of MD-2 positive cells in the IBS patients was 2.26
      (0.80-4.73)/view field, significantly higher than that of the healthy controls
      [0.90 (0.56-1.33)/view field, P = 0.003]. The positive rate of NF-kappa B of the
      IBS patients was 83.33%, significantly higher than that of the healthy controls
      (P = 0.02) and the NF-kappa B intensity of the IBS patients of the A value was
      (0.31 +/- 0.04), significantly higher than that of the healthy controls [(0.25 +/
      0.04), P = 0.003]. CONCLUSION: Up-regulation of TLR4 in IBS patients may
      contribute to occurrence of IBS. There exists the activation of the signal
      transduction pathway of NF-kappa B in the colonic mucosa of IBS patients, which
      suggested that inflammation participates in pathogenesis of IBS. The low and
      negative expression of MD-2 may contribute to the tolerance with the intestinal
      commensal bacteria.

PMID- 19159573
TI  - [Expression of guanylyl cyclase-c and caudal type homeobox transcription factor 2
      in human gastric cancer and precursor lesions].
AB  - OBJECTIVE: To investigate the expression of guanylyl cyclase-C (GC-C) and caudal
      type homeobox transcription factor 2 (CDX2) in human gastric mucosa at different
      stages and the significance thereof. METHODS: An Immunofluorescence method was
      used to detect the expression of GC-C and CDX-2 in 23 specimens of gastric
      carcinoma and matching noncancerous tissues. Western blotting was used to detect
      the protein expression of GC-C and CDX2 in the gastric carcinoma tissues and
      matching noncancerous tissues too. RESULTS: The GC-C and CDX2 expression rates
      were 39.1% and 39.1% respectively in the intestinal metaplasia specimens, 55.6%
      and 55.6% respectively in the dysplasia specimens, and 56.7 % and 60.0% in the
      gastric carcinoma specimens, all significantly higher than those in the normal
      mucosa specimens (all P = 0.000) without significant differences in the
      expression of GC-C and CDX-2 among the 3 pathological groups. The GC-C and CDX-2
      expression was positively correlated with Lauren classification, The expression
      levels of GC-C and CDX-2 were significantly higher in the intestinal-type than in
      the diffuse-type gastric carcinoma (P < 0.05). The GC-C expression was positively
      correlated with the expression of CDX-2 in intestinal metaplasia and gastric
      carcinoma. CONCLUSION: Ectopic expression of GC-C and CDX2 in human gastric
      mucosa may play an important role in the carcinogenesis of intestinal-type
      gastric carcinoma. Detection of GC-C and CDX2 helps diagnose gastric carcinoma
      and precursor lesions.

PMID- 19159574
TI  - [Diagnostic significance of serum allergen detection in diagnosis of allergic
      rhinitis and bronchial asthma].
AB  - OBJECTIVE: To analyze the diagnostic significance of serum total IgE, specific
      IgE (SIgE), Phadiatop, and eosinophil cationic protein (ECP) in allergic rhinitis
      and bronchial asthma. METHODS: The serum total IgE, SIgE , and Phadiatop were
      tested in 122 patients with allergic rhinitis. The ECP, SIgE, and Phadiatop were
      tested in 135 patients with bronchial asthma. Forty healthy persons were used as
      controls. The serum total IgE were tested by electrochemiluminescence. The serum
      Phadiatop, ECP, and SIgE were tested by fluorescent-enzyme linked immunosorbent
      assay. RESULTS: The serum total IgE positive rate of the 122 allergic rhinitis
      patients was 37.7%, significantly higher than that of the healthy controls (2.5%,
      chi2 = 18.13, P < 0.01). The specificity of total IgE of the allergic rhinitis
      patients were 97.5%. The serum ECP positive rate of the bronchial asthma patients
      was 65.9%, significantly higher than that of the healthy controls (20.0%, chi2 =
      26.34, P < 0.01). The sensitivity and specificity of the bronchial asthma
      patients were 65.9% and 80.0%. The Phadiatop positive rates of the allergic
      rhinitis and the bronchial asthma patients were 50.0% and 31.9% respectively,
      both significantly higher than that of the control (0, chi2 = 32.08, 16.89, both
      P < 0.01). Most kinds of SIgE were from the allergens, such as dust mite, dust,
      and Artemisia etc. CONCLUSION: Increase of serum ECP level is an important
      indicator of airway inflammation activity and inflammation serious degree in the
      bronchial asthma patients. The increase of serum total IgE has an important
      diagnostic significance in allergic rhinitis. It is important to detect SIgE and
      Phadiatop in diagnosis and monitoring of allergic rhinitis and bronchial asthma.

PMID- 19159575
TI  - [Clinical profiles and surgical outcomes of coronary obstruction due to type A
      aortic dissection: a single institution experience].
AB  - OBJECTIVE: To investigate the clinical profile of myocardial infarction (MI) due
      to retrograde aortic dissection of aortic root and the relevant predictors of in
      hospital death. METHODS: The clinical data of 207 consecutive patients with type
      A aortic dissection (AD), who were hospitalized and underwent operation between
      December 2003 and October 2007, were analyzed retrospectively. RESULTS: Eight of
      the 207 patients were diagnosed as with MI due to retrograde aortic dissection of
      aortic root, 6 males and 2 females, aged (49 +/- 14). Surgical repair of the
      aorta and coronary revascularization was implanted: ascending aorta replacement
      in 2 cases, hemi-arch replacement in 5 cases, arch replacement in 1 case;
      coronary artery bypass grafting in 5 cases, and coronary repair in 3 cases. In
      hospital death occurred in 4 of the 8 patients (50%) who all had preoperative
      renal insufficiency and developed acute renal failure (ARF) after surgery.
      Univariate analysis identified preoperative renal insufficiency an independent
      predictor of in-hospital death (The preoperative serum creatinine (sCr) level of
      the surviving patients was (80 +/- 30) micromol/L, significantly lower than that
      of the deceased patients [(176 +/- 67) micromol/L, P = 0.02]. There were no
      significant differences in other parameters between the surviving and deceased
      groups. CONCLUSION: MI due to type A AD is associated with high operative
      mortality. Preoperative renal insufficiency attributes to development of ARF
      after surgery and the unfavorable outcome. Renal function before surgery is
      essential for risk stratification in this lethal condition.

PMID- 19159576
TI  - [Effects of recombinant adenovirus-mediated double suicide genes on implanted
      human keloid: experiment with athymic mice].
AB  - OBJECTIVE: To detect the effects of the recombinant adenovirus-mediated double
      suicide genes constructed by Escherichia coli cytosine deaminase (CD)/5
      fluorocytosine (5-Fc) and herpes simplex virus-thymidine kinase (HSV
      TK)/ganciclovir (GCV)-CDglyTK on implanted human keloids and mechanisms thereof.
      METHODS: Twenty nude mice were implanted with human keloid obtained during
      operation so as to establish mouse keloid models and then were randomly divided
      into 4 equal groups: Group A, injected with normal saline (NS) into the keloid
      once per 3 days for 18 days totally, Group B injected with NS into the keloid and
      injected intraperitoneally with 5-Fc and GCV; Group C injected with CDglyTK into
      the keloid, and Group D injected with CDglyTK into the keloid and 5-Fc and GCV
      injected intraperitoneally. The volume of the implanted keloid tissue was
      measured 2, 7, 14, 21, 28, 35, and 42 days after operation. On day 42 the keloid
      tissues were removed to undergo morphological examination, TUNEL method was used
      to examine the apoptosis of the fibroblasts, and the expression of Bcl-2 and BAX,
      products of apoptosis-related genes, were detected by immunohistochemistry.
      RESULTS: Compared to those before treatment the volume of the implanted keloid of
      Group D began to decrease since 14 days after treatment time-dependently (all P <
      0.05), and the volumes of the other 3 groups continued to increase and peaked on
      days 21, 14, or 7 respectively (all P < 0.05). Microscopy showed infiltration of
      a larger quantity of histiocyte in the keloid tissue, and more obvious collagen
      disorganization and apoptosis of fibroblasts in Group D than in the other 3
      groups. The protein expression of Bcl-2 was more remarkable and the protein
      expression of BAX was less remarkable in Group D than in the other 3 groups.
      CONCLUSIONS: The recombinant adenovirus-mediated double suicide gene therapy is
      effective on the implanted keloid tissue. The main mechanism may be induction of
      apoptosis in the keloid fibroblasts.

PMID- 19159577
TI  - [Inhibition of CD40L induced E-selectin expression in endothelial cells through
      extracellular signal-regulated kinase signaling pathway].
AB  - OBJECTIVE: To investigate the regulatory effects of atorvastatin on CD40L induced
      E-selectin expression in endothelial cells and the association thereof with
      signal pathway. METHODS: Human umbilical vein endothelial cells (HUVECs) were
      obtained from umbilical cord newly delivered and incubated with CD40L for 24
      hours with or without pretreated by atorvastatin of the concentrations of 0.1, 1,
      or 10 micromol/L. The protein and mRNA levels of E-selectin were detected by flow
      cytometry and reverse transcription polymerase chain reaction (RT-PCR)
      respectively. The extracellular signal regulated kinase (ERK) 1/2 activation was
      analyzed by Western blotting. RESULTS: The E-selectin mRNA expression level of
      the HUVECs treated by atorvastatin was lower than that of the CD40L stimulation
      group by 33.33% when the atorvastatin concentration was 1 micromol/L, and was
      lower by 45.16% when the atorvastatin concentration was 10 micromol/L. The E
      selectin protein expression level of the HUVECs treated by atorvastatin was lower
      than that of the CD40L stimulation group by 48.68% when the atorvastatin
      concentration was 1 micromol/L, and was lower by 70.25% when the atorvastatin
      concentration was 10 micromol/L. The phosphorylation level of ERK1/2 was enhanced
      by CD40L stimulation and the CD40L induced phosphorylation of ERK1/2 decreased by
      81% +/- 6%, 73% +/- 5%, and 41% +/- 5% respectively after atorvastatin
      stimulation. CONCLUSION: Atorvastatin decreases the CD40L induced E-selectin
      expression in endothelial cells while atorvastatin at 0.1-10 micromol/L
      concentration-dependently through inhibiting the activation of ERK1/2.

PMID- 19159578
TI  - [Effect of Lactobacillus rhamnosus GG on immune response: experiment with
      autoimmune mice induced by Campylobacter jejuni].
AB  - OBJECTIVE: To investigate the immune effects of Lactobacillus rhamnosus GG (LGG)
      on immune response. METHODS: Fourty ICR mice were randomly divided into 4 groups,
      normal control (N) group, model (M) group, Lactobacillus (LGG) group, and
      hydrocortisone (HC) group. The mice were induced by Campylobacter jejuni with
      complete Freund's adjuvant as autoimmune animal model except N group. From the
      fifteenth day after primary immunization, each group was given different
      administration through peritoneum route for 7 days. Twenty-five days after the
      model establishment, the mice were killed. Then the blood sample was collected
      the undergo ELISA to detect the level of ds-DNA antibody and interferon (IFN)
      gamma. The proliferation activities of the B and T cells were examined. The
      livers and kidneys were taken out to undergo microscopy. RESULTS: The ds-DNA
      antibody levels of the HC and LGG groups were not significant different from that
      of the M group (both P > 0.05). The proliferation activities of T and B cells and
      IFN-gamma level of the groups LGG were all significantly lower than those of the
      group M [0.42 +/- 0.05 vs 0.60 +/- 0.09, 0.43 +/- 0.05 vs 0.60 +/- 0.09, (184 +/-
      16) vs (195 +/- 6) pg/ml, all P < 0.01]. CONCLUSION: LGG inhibits the immune
      response induced by CJ to a certain degree.

PMID- 19159580
TI  - [Effects of Shen-song-yang-xin capsule on ventricular arrhythmias in
      ischemia/reperfusion: experiment with rats].
AB  - OBJECTIVE: To investigate the effects of Shen-song-yang-xin capsule containing
      ginseng, ophiopogon root, red sage root, etc, on the ventricular arrhythmias
      caused by ischemic/reperfusion. METHODS: Thirty SD rats were randomly divided
      into 2 equal groups: Shen-song-yang-xin group undergoing gastric infusion of Shen
      song-yang-xin 4 g x kg(-1) x d(-1) for 2 weeks and then subjected to left
      coronary artery occlusion for 30 minutes followed by reperfusion for 60 minutes,
      and control group undergoing ischemia/reperfusion only. Electrocardiography was
      conducted to record the ventricular arrhythmias, and after 60 minutes of
      reperfusion the rats were killed with their hearts removed to measure the
      infarction size. RESULTS: (1) During the 30 minutes' ischemia, the average number
      of episode of ischemia-induced premature ventricular contraction of the Shen-song
      yang-xin group was (6.7 +/- 0.3) beats/30 min, significantly lower than that of
      the control group [(15.0 +/- 1.1) beats/30 min, P = 0.007]; the average number of
      episode of ischemia-induced ventricular tachycardia of the Shen-song-yang-xin
      group was (3.5 +/- 0.2) episodes/30 min, significantly lower than that of the
      control group [(14.7 +/- 0.6) episodes/30 min, P = 0.003]; the duration of
      ventricular tachycardia of the Shen-song-yang-xin group was (10.3 +/- 2.0) s,
      significantly shorter than that of the control group [(28.3 +/- 4.6) s, P =
      0.018]; and the duration of ventricular fibrillation of the Shen-song-yang-xin
      group was (7.0 +/- 1.1) s, significantly shorter than that of the control group
      [(15.0 +/- 1.7) s, P = 0.031]. (2) 60 minutes after the reperfusion, the number
      of episode of premature ventricular contraction of the Shen-song-yang-xin group
      was (5.3 +/- 0.8) beats/60 min, significantly lower than that of the control
      group [(15.6 +/- 1.8) beats/60 min, P = 0.002], and the duration of reperfusion
      induced ventricular tachycardia was (4.6 +/- 0.5) s, significantly shorter than
      that of the control group [(13.5 +/- 0.6) s, P = 0.001]. CONCLUSION: Shen-song
      yang-xin capsule significantly reduces the ischemia-induced ventricular
      arrhythmia, average episode number of reperfusion-induced premature ventricular
      contraction, and duration of reperfusion-induced ventricular tachycardia.

PMID- 19159587
TI  - [Stem cells transplantation for inflammatory bowel].

PMID- 19159581
TI  - [Effects of overexpression of decorin on matrix metalloproteinases 2 and 9 in rat
      mesangial and tubular cells].
AB  - OBJECTIVE: To investigate the effects of overexpression of decorin (DCN), one of
      the small leucine-rich proteoglycans, on the expression of extracellular matrix
      molecules in glomerular mesangial and tubular cells. METHODS: Recombinant
      adenovirus vector containing DCN gene (Ad/DCN) was constructed, and recombinant
      adenovirus containing LacZ gene (Ad/LacZ) was used as control vector. Rat renal
      glomerular mesangial cells of the line RMC and tubular cells of the line HK-2
      were cultured and divided into following groups: high glucose + Ad/DCN
      transfection (experimental), high glucose + Ad/LacZ transfection (vector
      control), high glucose + neutralizing antibody against transforming growth factor
      (TGF)-beta 1 (positive control), high glucose non-transfection (PBS control), and
      low glucose culture (normal control) groups. Western blotting was used to detect
      the protein expression of decorin, TGF-beta 1, collagen type IV, MMP-2, and MMP
      9. RESULTS: The DCN protein expression was low only in the low glucose group, and
      was up-regulated in other groups, especially in the Ad/DCN group, so as the
      expression of TGF-beta 1 and collagen type IV, while the ratio of TGF-beta 1 to
      decorin is increased in both RMC and HK-2 cells. The expression levels of MMP-2
      and MMP-9 decreased in the high-glucose-cultured RMC cells and increased in the
      high-glucose-cultured HK-2 cells, however, adenovirus-mediated transfection of
      decorin gene reversed all of these changes, and had almost the same effects on
      reducing the protein expression of TGF-beta 1 collagen type IV, MMP-2, and MMP-9
      as anti-TGF-beta 1 antibody. CONCLUSION: The agents increasing the decorin
      expression in mesangial and tubular cells may help prevent the development and
      progression of diabetic nephropathy. Overexpression of decorin may be a useful
      tool for developing new therapeutic application for the treatment of diabetic
      nephropathy.

PMID- 19159588
TI  - [Bio-target therapy for refractory ulcerative colitis].

PMID- 19159590
TI  - [Relationship between expression of inhibitory killer cell immunoglobulin-like
      receptor HLA-Cw ligand and susceptibility to inflammatory bowel disease].
AB  - OBJECTIVE: To investigate the distribution of different phenotypes of inhibitory
      killer cell immunoglobulin-like receptor (iKIR) and its ligand HLA-Cw in patients
      with inflammatory bowel disease (IBD), and to explore whether iKIR/HLA-Cw
      combinations are associated with IBD susceptibility. METHODS: Peripheral blood
      samples were collected from 100 patients with ulcerative colitis (UC), 73
      patients with Crohn's disease, and 106 randomly selected ethnically matched
      healthy controls. Polymerase chain reaction with sequence-specific primers was
      used to analyze the iKIR phenotypes, and the HLA-Cw phenotypes was examined with
      HLA-C LOCUS SSP UNITRAY kit, and the combination of HLA-Cw and its corresponding
      iKIR in individual was analyzed subsequently. RESULTS: The KIR2DL1 and KIR2DL3
      gene phenotype frequencies in UC patients were 0.710 and 0.620 respectively, both
      significantly lower than those in healthy controls (0.896, chi(2) = 11.405 P =
      0.001, and 0.821, chi(2) = 10.362 P = 0.001 respectively). The KIR2DL1 gene
      phenotype frequency in CD patients was 0.740, significantly lower than that in
      healthy controls (0.896, chi(2) = 7.589, P = 0.006). The KIR2DL1 HLA-C2
      combination (2DL1(+)-HLA-C2(+)) in UC patients and CD patients were 0.380 and
      0.411 respectively, both significantly lower than that in healthy controls
      (0.575, chi(2) = 7.876 P = 0.005 and 0.575, chi(2) = 4.681 P = 0.030
      respectively). CONCLUSION: The susceptibility to IBD is associated with decreased
      KIR2DL1-HLA-C2 combination.

PMID- 19159591
TI  - [Impact of secondary lymphoid tissue chemokine on lymphocyte migration and the
      significance thereof in pathogenesis of ulcerative colitis: experiment with
      rats].
AB  - OBJECTIVE: To explore the impact of secondary lymphoid tissue chemokine (SLC) on
      lymphocyte migration and the significance thereof in the pathogenesis of
      ulcerative colitis (UC). METHODS: Sixty SD rats were randomly divided into 3
      equal groups: model group undergoing dripping of 40% acetone solution of dinitro
      chlorobenzene (DNCB) on the back for 2 weeks and then enema of 6% DNCB acetone
      solution so as to establish models of UC, and then intravenous injection of
      normal saline (NS) for 5 days; SLC antibody intervention group undergoing
      intravenous injection of SLC antibody 15 microg x ml(-1) x kg(-1) immediately
      after the establishing of model; and control group undergoing enema of NS nly and
      then intravenous injection of NS for 5 days. Six days after the establishing of
      model venous blood samples were collected from the portal veins of the 3 groups.
      Lymphocytes were isolated and cultured. RT-PCR was used to detect the mRNA
      expression of the SLC receptor CCR7. Boyden chamber system was used to examine
      the migration ability of the lymphocytes exposed to SLC of 20, 40, 60, 80, and
      100 ng/ml respectively. ELISA was used to detect the expression of interleukin
      (IL)-10 and interferon (IFN)-gamma in the supernatants of the lymphocytes of
      different groups. RESULTS: RT-PCR showed that the CCR7 mRNA expression level of
      the model group was (0.792 +/- 0.108), significantly higher than that of the
      intervention group (0.386 +/- 0.115, P = 0.0429), and the CCR7 mRNA expression
      levels of these 2 groups were both significantly higher than that of the control
      group (0.106 +/- 0.029, both P < 0.01). SLC dose-dependently promoted the
      migration ability of the lymphocytes, but there existed a saturation phenomenon.
      Exposed to 80 ng/ml SLC the migration level of the lymphocytes of the model group
      peaked to (85.9 +/- 16.0), 3.7 times as high as that of the control group (20.5
      +/- 1.8, P < 0.01), and the migration level of the lymphocytes of the
      intervention group was 38.2 +/- 6.3, significantly higher than that of the
      control group too (P < 0.05). SLC enhanced the expression of IFN-gamma of the
      lymphocytes of the model group, while reduced the IL-10 level, and both effects
      peaked at the concentration of 80 ng/ml (P = 0.042, P = 0.036). CONCLUSION: SLC
      promotes the lymphocyte migration and boosts the differentiation of lymphocytes,
      thus participating in the pathogenesis of UC.

PMID- 19159592
TI  - [Diagnostic value of antineutrophil cytoplasmic antibodies in patients with
      ulcerative colitis: a meta-analysis].
AB  - OBJECTIVE: To evaluate the diagnostic value of antineutrophil cytoplasmic
      antibodies (ANCA) in patients with ulcerative colitis (UC). METHODS: Articles
      related to diagnosis of UC by ANCA test, published before November 2007, were
      retrieved in the databanks such as Chinese BioMedical Disc, Chinese Medical
      Current Contents, China National Knowledge Infrastructure, and VIP databank.
      Related journals were searched manually. Meta-analysis was performed by summary
      receiver operating characteristic curve recommended by Diagnostic and Screening
      Group of the Cochrane Collaboration Web with the parameters such as sensitivity,
      specificity, accuracy, predictive values and likelihood ratio. RESULTS: Totally
      10 studies including 381 patients met the inclusion criteria. Meta-analysis
      showed that the sensitivity and specificity of ANCA to the diagnosis of UC were
      52.2% and 99.0% respectively. The positive and negative predictive values (PPV
      and NPV) were 98.0% and 68.7% respectively. Meanwhile, the positive and negative
      likelihood ratio (+LR and -LR) were 52.2 and 0.5, respectively. CONCLUSIONS: ANCA
      is an immunological index related to UC. Positive ANCA helps diagnose UC, but is
      not sensible enough to screen UC.

PMID- 19159593
TI  - [Genetic heterogeneity of myosin heavy chain 7 gene G823E mutation in familial
      hypertrophic cardiomyopathy in Chinese].
AB  - OBJECTIVE: To study the disease-causing gene mutations in familial hypertrophic
      cardiomyopathy (HCM) in Chinese and to reveal the relationship between the
      genotype and the phenotype. METHODS: Peripheral blood samples were collected from
      12 members of a HCM family, and 120 healthy volunteers in China. PCR and double
      deoxygenation chain termination method were used to analyze the cardiac troponin
      T gene (TNNT2), beta-myosin heavy chain gene (MYH7) gene and myosin binding
      protein C gene (MYBPC3) and to detect mutations. RESULTS: Mutation G14452A was
      identified in exon 22 of MYH7 gene in 4 family members, causing the conversion of
      glycine (G) into glutamic acid (E). The onset ages and clinical manifestations of
      the family members carrying the mutation G823E, including 2 patients (the
      proband, male, with the onset age of 51, and his 26-year-old second son with the
      onset age of 20), and 2 carriers (his 31-year-old elder son and 29-year-old elder
      daughter), presented significant individual differences. CONCLUSIONS: The G823E
      mutation of MYH7 gene is the causal mutation of familial HCM. The heterogeneity
      of phenotypes suggests that multiple factors may be involved in the pathogenesis
      of HCM.

PMID- 19159594
TI  - [Epstein-Barr virus-associated pneumonia in patients with post-transplant
      lymphoproliferative disease after hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To investigate the clinical features of Epstein-Barr virus (EBV)
      reactivation or infection-induced post-transplant lymphoproliferative disease
      (PTLD) and EBV-associated pneumonia after hematopoietic stem cell transplantation
      (HSCT). METHODS: The clinical data of 7 patients with PTLD, 6 from the 239
      patients undergoing allo-HSCT and 1 from the 84 patients undergoing auto-HSCT,
      were analyzed. RESULTS: All the 7 patients had extravisceral lymph node
      enlargement as the primary presentation. Five cases were diagnosed as with
      diffuse large B-cell lymphoma, 1 case as with polymorphic B-cell hyperplasia, and
      1 case peripheral T-cell lymphoma-unspecified. Sex chromosome analysis showed
      that the tumor cells originated from the donors. ELISA showed that plasma EBV DNA
      was positive in 6 of the 7 patients and was negative in 1 patient. Chest CT
      revealed multifocal patches and diffuse ground-glass attenuation in both lungs.
      EBV-DNA was positive in the bronchoalveolar lavage (BAL) fluid. The T cells in
      all of the BAL fluid were mainly CD3+ T cells without CD19+ and CD20+ B cells.
      Lung biopsy showed interstitial and intra-alveolar infiltration, constituted
      mainly by CD3+ T cells and partly by CD68+ macrophages, however, without CD19+
      and CD20+ B cells. The 3 patients with PTLD accompanied by EBV associated
      pneumonia had hyperpyrexia and dyspnea, and their condition aggravated rapidly
      and eventually all the 3 patients died of respiratory failure, of which 1 case
      with multiple organ failure died within 2 weeks since the onset of PTLD.
      CONCLUSIONS: EBV-associated PTLD accompanied by EBV-associated pneumonia is not
      rare and is always severe. Cytology of BAL fluid and lung biopsy help diagnose.

PMID- 19159595
TI  - [Effects of 4-hydroxytamoxifen on prostate smooth muscle cells: an in vitro
      experiment].
AB  - OBJECTIVE: To investigate the effects of 4- hydroxytamoxifen (OHT) on the
      proliferation and apoptosis of prostate smooth muscle cells and the expression of
      estrogen receptor (ER) and androgen receptor (AR). METHODS: Prostate smooth
      muscle cells were isolated from the resected specimens of prostate glands of 10
      patients with benign prostatic hypertrophy (BPH), cultured, and exposed to
      estradiol (E(2)), diethylstilbestrol (DES), and OHT of different concentrations
      (1 x 10(-8) - 1 x 10(-5) mol/L) or mixture of E(2) (1 x 10(-8) - 1 x 10(-6)
      mol/L) with OHT (1 x 10(-7) mol/L). Flow cytometry was used to test the
      proliferation and apoptosis of the cells, and immunocytochemistry was used to
      test the expression of estrogen and androgen receptors. RESULTS: E(2) and DES
      promoted the proliferation of the prostate smooth muscle cells in a certain
      concentration range, but not dose-dependently, and OHT at the concentration of 1
      x 10(-8) mol/L slightly increased the G(2)-M peak rate of the prostate smooth
      muscle cells, but suppressed the G(2)-M peak rate dose-dependently when its
      concentration was >or= 1 x 10(-7) mol/L (P < 0.05) and this suppression effect
      was dose-dependently (r = -0.312, P = 0.011). E(2) at the concentration >or= 1 x
      10(-5) mol/L and DES at the concentration >or= 1 x 10(-6) mol/L slightly promoted
      the apoptosis of the prostate smooth muscle cells, but not dose-dependently, and
      OHT at the concentrations from 1 x 10(-8) mol/L to 1 x 10(-5) mol/L promoted the
      apoptosis of the prostate smooth muscle cells dose-dependently (r = 0.363, P =
      0.021) and this effect could not be reversed by administration of E(2) at the
      concentration 1 x 10(-8) - 1 x 10(-6) mol/L (P > 0.05). E(2), DES, and OHT of
      different concentrations all increased the ERalpha and AR positive staining rates
      of the prostate smooth muscle cells (all P < 0.05). CONCLUSIONS: OHT suppresses
      the proliferation and promotes the apoptosis of prostate smooth muscle cells, and
      these functions do not depend on the estrogen receptor pathway. Low blood OHT
      concentration after oral administration of TAM and up-regulation of estrogen
      receptors by OHT may be the caused of the inefficiency of TAM for treatment of
      BPH.

PMID- 19159596
TI  - [Effects of transketolase-like gene TKTL1 on occurrence and metastasis of human
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the effects of transketolase-like gene TKTL1 on the
      occurrence and metastasis of human nasopharyngeal carcinoma (NPC). METHODS: Real
      time PCR was used to determine the mRNA expression levels of transketolase gene
      family (TKT, TKTL1, and TKTL2) in the 65 biopsy specimens of human nasopharyngeal
      carcinoma, 9 at stage I, 15 at stage II, 16 at stage III, 13 at stage IVA, and 12
      at stage IVB, 42 with metastasis and 232 without metastasis, and 9 biopsy
      specimens of chronic nasopharyngitis. RESULTS: The TKL activity level of the NPC
      tissues was 21.6 +/- 2.8, significantly higher than that of the chronic
      nasopharyngitis tissues (6.2 +/- 1.3, P < 0.01). The TKL activity level of the
      NPC tissues with metastasis was 26.5 +/- 3.2, significantly higher than that of
      the NPC tissues without metastasis (17.6 +/- 2.1, P < 0.01). There was no
      significant difference in the expression levels of TKT and TKTL2 genes between
      the human NPC and chronic nasopharyngitis tissues (both P > 0.05). The expression
      level of TKTL1 gene in the NPC tissues was 5.25 +/- 0.32, significantly higher
      than that in the chronic nasopharyngitis tissues (0.98 +/- 0.11, t = 6.23, P <
      0.01), and the expression level of TKTL1 gene in the NPC tissues with lymph node
      metastasis was 5.86 +/- 0.38, significantly higher than that in the NPC tissues
      without lymph node metastasis (4.18 +/- 0.22, t = 3.28, P < 0.01). CONCLUSION:
      TKTL1 may play an important role in the occurrence and metastasis of human NPC
      and become a potential target for novel anti-cancer therapy.

PMID- 19159597
TI  - [Long-term survival after liver transplantation for benign end-stage liver
      disease in adults].
AB  - OBJECTIVE: To evaluate the long-term survival rates of the adults with benign end
      stage liver disease (BELD) after liver transplantation (LT) and the causes of
      death. METHODS: The common causes of late death (after more than 1 year) after LT
      were retrospectively analyzed in 203 consecutive patients with BELD who underwent
      LT from Oct. 2003 to May.2006. RESULTS: The 1, 2 and 3-year survival rates were
      88.7%, 85.5%, and 81.2% respectively. The 2-year and 3-year survival rates of the
      patients with HBV-related liver disease were 88.4% and 84.5% respectively, not
      significantly different from those of patients with non-HBV-related liver disease
      (75.6% and 64.0% respectively, P = 0.144). 165 recipients survived for more than
      1 year and 21 recipients died during the period between 12 and 48 months after LT
      with a mean of (22.7 +/- 6.6) months. The common causes of late death included
      related to infectious complications (4.8%, 8/165), biliary tract complications
      (3.6%, 6/165), HBV re-infection (1.8%, 3/165), chronic rejection (1.2%, 2/165),
      renal functional lesion (0.6%, 1/165), and hepatic arterial complication
      (0.6%1/165). CONCLUSION: Satisfactory long-term survival can be achieved in most
      adult recipients with BELD after LT and the major causes that influence the long
      term survival are infectious complications, biliary tract complications, and HBV
      re-infection. Prevention of these complications, rational use of
      immunosuppressant, and regular follow-up are essential to improve long-term
      survival.

PMID- 19159598
TI  - [Prevention and treatment of biliary tract complications following adult living
      donor liver transplantation].
AB  - OBJECTIVE: To investigate the prevention and treatment of biliary tract
      complications following adult-adult living donor liver transplantation (A-A
      LDLT). METHODS: One hundred and eight patients, aged 38 (18 - 63), underwent A-A
      LDLT, including transplantation of the right liver graft without middle hepatic
      vein (MHV) in 102 cases and dual graft transplantation in 6 cases (of left lobe
      from relative in 1 case, of right lobe+left lobe from relative in 3 cases, of
      right lobe from relative + cadaveric left lobe in 2 cases). Preoperative 3
      dimensional computerized tomography (3D CT) and intra-operative cholangiography
      were employed to reveal the state of the liver, caution was exercised to protect
      the peripheral vasculature of the right hepatic duct during resection. The bile
      duct was reconstructed by duct-to-duct (D-D) biliary anastomosis or Roux-en-Y
      anastomosis of the hepatic duct and jejunum (H-J). RESULTS: Twenty-four of the
      108 patients (22.2%) suffered from complications, including bile leakage (n = 4),
      cutting surface bile leakage (n = 1), and anastomotic biliary stricture (n = 3),
      etc. Seven donors (6.3%) suffered from complications too, including 2 cases of
      bile leakage from the remnant cut surface. All the biliary tract complications
      were properly managed with good outcomes, except for 1 case of recipient death.
      CONCLUSION: Measures such as improvement of pre- and intra-surgical examinations
      and assessments, choice of appropriate approach of biliary tract reconstruction,
      employment of subtle operations of microscopic procedures, and timely detection
      and management of complications may reduce the incidence and mortality of biliary
      tract complications following A-A LDLT.

PMID- 19159599
TI  - [Diagnosis and treatment of pulmonary hypertension caused by sleep
      hypoventilation: analysis of 4 cases in a family].
AB  - OBJECTIVE: To summarize the experience in diagnosis and treatment of pulmonary
      hypertension caused by sleep hypoventilation. METHODS: The clinical data of 4
      patients in a family with pulmonary hypertension caused by sleep hypoventilation,
      full brothers and sisters, 2 (Cases 1 and 2) being treated presently and 2 (Cases
      3 and 4) being deceased and traced by family medical history, were
      retrospectively analyzed. RESULTS: Three of the 4 cases (cases 1, 3, and 4) were
      misdiagnosed as with cor pulmonale combined with pulmonary hypertension, and one
      case (case 2) was misdiagnosed as with primary pulmonary hypertension.
      Polysomnography (PSG) revealed alveolar hypoventilation-induced long period of
      oxygen desaturation at sleep in Cases 1 and 2, thus confirming the diagnosis.
      Pulmonary function test showed that the percentage of maximum inspiratory
      pressure (PImax) in predicted value (51.5% and 20.9%) and the maximum expiratory
      pressure (PEmax) in predicted value (51.3% and 29.6%) decreased, the percentage
      of mouth occlusion pressure (P0.1) in predicted value (141% and 133%)
      compensatively increased, and the respiratory muscle strength decreased in Cases
      1 and 2, which suggested that there was neuromuscular disorder in these patients.
      Treated by noninvasive ventilation the symptoms of these 2 patients were improved
      and they were discharge at last. Subsequently, they were treated by long-term
      night noninvasive ventilation at home, and returned to normal work and life.
      During the follow-up for 22 and 12 months respectively after discharge, PSG
      showed that the alveolar hypoventilation-induced long period oxygen desaturation
      at sleep had been greatly improved, and echocardiogram showed that the pulmonary
      pressure was greatly decreased. CONCLUSION: For the patients with unexplained
      pulmonary hypertension, PSG monitoring and pulmonary function tests such as
      PImax, PEmax, and P0.1 help determine the etiology, and long-term night
      noninvasive ventilation at home can improve the outcome of sleep hypoventilation
      induced pulmonary hypertension.

PMID- 19159600
TI  - [Significance of IGS1, ITS and D1/D2 regions in molecular identification of
      Trichosporon species and genotype of T. asahii in China].
AB  - OBJECTIVE: To compare the sensitivity and specificity in molecular identification
      in different DNA regions of Trichosporon species and to study the genotype of T.
      asahii isolated from clinical specimens in China. METHODS: DNA was extracted from
      the cells of all experimental strains by using a method of glass bead method. The
      D1/D2, ITS and IGS1 regions were amplified by PCR with specific primers, the PCR
      products were cloned and sequenced. The sequences were referred to GenBank and
      compared with the other sequences of the Trichosporon species from GenBank by the
      software CLUSTAL X 1.83. Phylogenetic trees were constructed and genotypes were
      determined. RESULTS: The D1/D2 regions in T. asahii (CBS2479), T. dermatis, and
      T. laibachii were 640, 639, and 637 bp in length respectively, the ITS regions
      were 541, 528, and 531 bp respectively in length, and the IGS1 regions were 643,
      515, and 411 bp respectively. The sequence similarity of the D1/D2 region was 89%
      - 99%, that of ITS and IGS1 regions were 85% - 99% and 11% - 95% respectively.
      The clinically isolated strains BZP07001, BZP07002, BZP07004, and BZP07005
      belonged to genotype I, and the strain BZP07003 to genotype IV. CONCLUSION: The
      sensitivity and specificity of the IGS1 region was higher than those of the D1/D2
      and ITS regions in identification of phylogenetically closely related
      Trichosporon species. T. asahii isolated from clinical specimens in China belongs
      to either genotype I or genotype IV.

PMID- 19159601
TI  - [Effects of early oral fluid resuscitation on organ functions and survival during
      shock stage in dogs with a 50% total body surface area full-thickness burn].
AB  - OBJECTIVE: To investigate the effects of early oral fluid resuscitation on organ
      functions and survival in severe burn shock. METHODS: Eighteen male Beagle dogs
      were surgically prepared for measurement, subjected to 50% total body surface
      area (TBSA) full-thickness flame injury 24 hours later, and then randomly divided
      into 3 equal groups: oral fluid resuscitation group (OR group) undergoing gastric
      infusion of glucose-electrolyte solution(GES)according to Parkland formula 0.5
      hour after burn with the dose of 4 ml x kg(-1).%TBSA(-1), 1/2 being given in the
      first 8 h and 1/2 in the latter 16 h. Intravenous (IV) resuscitation of GES group
      (VR group) undergoing IV infusion of GES with the same dose as mentioned above,
      and no fluid resuscitation (NR) group given with GES during the first 24 h. In
      the second 24 hours all dogs received IV fluid resuscitation. At the end of 72
      hours-period experiment, the mortality was recorded. The mean arterial pressure
      (MAP), plasma blood volume (PV), hematocrit (HCT), urinary output, alanine
      aminotransferase (ALT), creatinine (Cr), and MB isoenzyme of creatine kinase (CK
      MB) were examined before injury and at 2, 4, 8, 24, 48 and 72 hours after injury.
      RESULTS: At the end of 72-hours-period experiment, all dogs died in the NR group,
      3 dogs died in the OR group, and no dog died in the VR group. The MAP and PV were
      significantly reduced after burn compared with those before-injury in the NR
      group, with the lowest levels of (34 +/- 9) mm Hg and (32.7 +/- 3.5) ml/kg (both
      P < 0.05) 8 h after burn, and the HCT, ALT, Cr, and CK-MB levels of the NR group
      peaked 8 h after burn to the levels of (61.7 +/- 2.7)%, (121.1 +/- 4.8) U/L,
      (91.0 +/- 6.1) micromol/L, and (13 891 +/- 297) U/L respectively. Eight hours
      after burn 4 dogs of the NR group showed anuria, and the rest two had the urine
      volume of 1.2 and 2.1 ml/kg respectively. Eight hours after burn the MAP, PV, and
      urinary output levels of the OR group were (84.3 +/- 17.1) mm Hg, (41.7 +/- 3.6)
      ml/kg, and (2.6 +/- 1.8) ml/kg respectively, all significantly higher than those
      of the NR group (all P < 0.05), but significantly lower than those of the VR
      group [(113.0 +/- 10.0) mm Hg, (50.3 +/- 5.2) ml/kg, and (7.0 +/- 1.9) ml/kg
      respectively, all P < 0.05]. The plasma ALT level of the OR group was (81.4 +/-
      10.8) U/L, significantly lower than that of the NR group (P < 0.05), but
      significantly higher than that of the VR group [(66.3 +/- 7.6) U/L, P < 0.05].
      The levels of plasma ALT at other time points, as well as the Cr and CK-MB levels
      at all time points of the OR group were all significantly higher than those of
      the VR group (all P < 0.05). The MAP, PV, HCT and urinary output levels of the
      two resuscitation groups returned to the pre-injury levels 72 h after burn, but
      the ALT, Cr, and CK-MB levels were still significantly higher than the pre-injury
      levels. CONCLUSIONS: Although oral resuscitation with GES is not as efficient as
      IV resuscitation in 50%TBSA burn, it still can maintain the MAP and PV, protect
      the organ functions and reduce the mortality comparing to no resuscitation. Oral
      resuscitation may be an ideal alternative way of IV resuscitation, especially in
      wars or other site of mass casualties.

PMID- 19159602
TI  - [Attenuation of allergic contact dermatitis by Z-VAD-FMK, a broad caspase
      inhibitor: experiment with mice].
AB  - OBJECTIVE: To investigate the effects of N-benzyloxycarbonyl-Val-Ala-Asp
      fluoromethylketone (Z-VAD-FMK), a broad caspase inhibitor, on allergic contact
      dermatitis (ACD). METHODS: A Balb/c mouse was killed and its back skin was
      peeled, put into a Franz diffusion cell, and smeared with Z-VAD-FMK. High
      performance liquid chromatography was used to examine the permeation rate.
      Dinitro-fluorobenzene (DNFB) was applied on the depilated back of mice as inducer
      and then on the back-side of right ear as provocative agent 6 days later so as to
      establish mouse ACD models. Two hours after the provocation 24 mouse models were
      divided into 4 equal groups to undergo the application of Z-VAD-FMK at the
      concentration of 0.1, 0.5, 2.5, and 5 mmol/L on the back-side of right ear twice.
      PBS was applied in the negative control group. Then the mice were killed with
      their 2 ears cut off. Microscopy was used to measure the right ear swelling
      degree, and differences in weight and thickness between the 2 ears. ELISA was
      used to detect the levels of IL-2 and INF-gamma in the ear tissues. RESULTS: The
      transdermal permeation rates of Z-VAD-FMK at the time points 6, 12, and 24 h were
      2.15%, 9.62%, and 12.85% respectively. The right ear swelling degree, and
      differences in weight and thickness between the 2 ears in the 2.5 mmol/L Z-VAD
      FMK group were (12.5 +/- 1.4) x 10(-2) mm, (3.2 +/- 0.3) mg, and (11.8 +/- 1.3) x
      10(-2) mm respectively, all significantly lower than those of the negative
      control group [(19.1 +/- 2.0) x 10(-2) mm, (4.3 +/- 0.4) mg, and (16.8 +/- 1.7) x
      10(-2) mm, all P < 0.05]. The IL-2 and INF-gamma levels in the ear skin lesion of
      the 2.5 mmol/L Z-VAD-FMK group were (148 +/- 10) and (650 +/- 45) pg/ml
      respectively, both significantly lower than those of the negative control group
      [(205 +/- 18) and (1030 +/- 58) pg/ml, both P < 0.05]. CONCLUSION: Z-VAD-FMK can
      permeate through mouse skin and inhibit the activation and proliferation of T
      lymphocytes, leading to the inhibitory effect of contact allergic reaction.

PMID- 19159603
TI  - [Intravesical perfusion of recombinant adeno-associated virus-endostatin in
      treatment of bladder cancer: experiments with mice].
AB  - OBJECTIVE: To study the anti-tumor effect of intravesical perfusion of
      recombinant adeno-associated virus-endostatin (rAAV-ES) in treatment of bladder
      cancer. METHODS: Forty-five C57BL/6 mice underwent intravesical perfusion of
      mouse bladder cancer cells of the line MB49 so as to establish orthotopic murine
      bladder cancer models and were divided into 3 equal groups, 3 days later to
      undergo intravesical perfusion of rAAV-ES, rAAV-EYFP, and PBS respectively once
      per week for 6 times. The anti-tumor effect of rAAV-ES on the tumor bearing mice
      was studied. RESULTS: The tumor weight of the rAAV-ES group was (145 +/- 30) mg,
      significantly lighter than those of the rAAV-EYFP and PBS groups [(250 +/- 32) mg
      and (250 +/- 30) mg respectively, both P < 0.05]. The survival time of the rAAV
      ES-treated mice was (46 +/- 7) d, significantly longer than those of the rAAV
      EYFP- and PBS-treated groups [(38 +/- 7) d and (38 +/- 6) d respectively, both P
      < 0.05]. CONCLUSION: An effective biologic agent in bladder cancer gene therapy,
      intravesical treatment with rAAV-ES inhibits the angiogenesis, thus inhibiting
      the tumor formation and progression.

PMID- 19159609
TI  - The formation of peroxynitrite in the applied physiology of mitochondrial nitric
      oxide.
AB  - Mitochondria require nitric oxide ((.)NO) to exert a delicate control of
      metabolic rate as well as to regulate life functions, cell cycle activation and
      arrest, and apoptosis. All activities depend on the matrical (.)NO steady state
      concentration as provided by mitochondrial (mtNOS) and cytosolic sources (eNOS)
      and reduced by forming superoxide anion and H2O2 and a low peroxynirite (ONOO(-))
      yield. We review herein the biochemical pathways involved in the control of (.)NO
      mitochondrial level and its biological and physiological significance in hormone
      effects and aging. At high ()NO, the cost of this physiological regulation is
      that ONOO(-) excess will lead to nitrosation/nitration and oxidization of
      mitochondrial and cell proteins and lipids. The disruption of (.)NO modulation of
      mitochondrial respiration supports then, a platform for prevalent
      neurodegenerative and metabolic diseases.

PMID- 19159610
TI  - An attempt to prevent senescence: a mitochondrial approach.
AB  - Antioxidants specifically addressed to mitochondria have been studied to
      determine if they can decelerate senescence of organisms. For this purpose, a
      project has been established with participation of several research groups from
      Russia and some other countries. This paper summarizes the first results of the
      project. A new type of compounds (SkQs) comprising plastoquinone (an antioxidant
      moiety), a penetrating cation, and a decane or pentane linker has been
      synthesized. Using planar bilayer phospholipid membrane (BLM), we selected SkQ
      derivatives with the highest permeability, namely plastoquinonyl-decyl
      triphenylphosphonium (SkQ1), plastoquinonyl-decyl-rhodamine 19 (SkQR1), and
      methylplastoquinonyldecyltriphenylphosphonium (SkQ3). Anti- and prooxidant
      properties of these substances and also of ubiquinonyl-decyl-triphenylphosphonium
      (MitoQ) were tested in aqueous solution, detergent micelles, liposomes, BLM,
      isolated mitochondria, and cell cultures. In mitochondria, micromolar cationic
      quinone derivatives were found to be prooxidants, but at lower (sub-micromolar)
      concentrations they displayed antioxidant activity that decreases in the series
      SkQ1=SkQR1>SkQ3>MitoQ. SkQ1 was reduced by mitochondrial respiratory chain, i.e.
      it is a rechargeable antioxidant. Nanomolar SkQ1 specifically prevented oxidation
      of mitochondrial cardiolipin. In cell cultures, SkQR1, a fluorescent SkQ
      derivative, stained only one type of organelles, namely mitochondria. Extremely
      low concentrations of SkQ1 or SkQR1 arrested H(2)O(2)-induced apoptosis in human
      fibroblasts and HeLa cells. Higher concentrations of SkQ are required to block
      necrosis initiated by reactive oxygen species (ROS). In the fungus Podospora
      anserina, the crustacean Ceriodaphnia affinis, Drosophila, and mice, SkQ1
      prolonged lifespan, being especially effective at early and middle stages of
      aging. In mammals, the effect of SkQs on aging was accompanied by inhibition of
      development of such age-related diseases and traits as cataract, retinopathy,
      glaucoma, balding, canities, osteoporosis, involution of the thymus, hypothermia,
      torpor, peroxidation of lipids and proteins, etc. SkQ1 manifested a strong
      therapeutic action on some already pronounced retinopathies, in particular,
      congenital retinal dysplasia. With drops containing 250 nM SkQ1, vision was
      restored to 67 of 89 animals (dogs, cats, and horses) that became blind because
      of a retinopathy. Instillation of SkQ1-containing drops prevented the loss of
      sight in rabbits with experimental uveitis and restored vision to animals that
      had already become blind. A favorable effect of the same drops was also achieved
      in experimental glaucoma in rabbits. Moreover, the SkQ1 pretreatment of rats
      significantly decreased the H(2)O(2) or ischemia-induced arrhythmia of the
      isolated heart. SkQs strongly reduced the damaged area in myocardial infarction
      or stroke and prevented the death of animals from kidney ischemia. In p53(-/-)
      mice, 5 nmol/kgxday SkQ1 decreased the ROS level in the spleen and inhibited
      appearance of lymphomas to the same degree as million-fold higher concentration
      of conventional antioxidant NAC. Thus, SkQs look promising as potential tools for
      treatment of senescence and age-related diseases.

PMID- 19159611
TI  - Cell-cell junction formation: the role of Rap1 and Rap1 guanine nucleotide
      exchange factors.
AB  - Rap proteins are Ras-like small GTP-binding proteins that amongst others are
      involved in the control of cell-cell and cell-matrix adhesion. Several Rap
      guanine nucleotide exchange factors (RapGEFs) function to activate Rap. These
      multi-domain proteins, which include C3G, Epacs, PDZ-GEFs, RapGRPs and DOCK4, are
      regulated by various different stimuli and may function at different levels in
      junction formation. Downstream of Rap, a number of effector proteins have been
      implicated in junctional control, most notably the adaptor proteins AF6 and
      KRIT/CCM1. In this review, we will highlight the latest findings on the Rap
      signaling network in the control of epithelial and endothelial cell-cell
      junctions.

PMID- 19159612
TI  - CD151 regulates HGF-stimulated morphogenesis of human breast cancer cells.
AB  - We previously demonstrated that CD151 forms a functional complex with c-Met and
      integrin alpha3/alpha6 in human salivary gland cancer cells. In the current
      study, we investigated the involvement of CD151, c-Met, and integrin
      alpha3/alpha6 in the cellular morphogenesis of human breast cancer cells.
      Knockdown of CD151, integrin alpha3, or integrin alpha6 expression abolished
      branching morphogenesis. Decreased c-Met expression in these cells led to the
      formation of rudimentary networks and prevented their conversion. Furthermore,
      hepatocyte growth factor (HGF) promoted cellular morphogenesis by accelerating
      network reorganization. Immunoprecipitation revealed a specific association
      between CD151 and c-Met. The involvement of CD151 and integrin alpha3/alpha6 in
      HGF-dependent signaling was confirmed by the decreased Akt phosphorylation in
      cells lacking CD151, integrin alpha3, or integrin alpha6. Hence, the regulation
      of CD151 expression might contribute to changes in HGF/c-Met signaling and
      thereby modulate the phenotypic characteristics of cancer cells.

PMID- 19159613
TI  - Influence of domain architecture and codon usage pattern on the evolution of
      virulence factors of Vibrio cholerae.
AB  - Cholera remains a heavy burden to human health in some developing countries
      including India where sanitation is poor and health care is limited. After the
      publication of the complete genome sequence of Vibrio cholerae, the etiological
      agent of cholera, extensive possibilities, earlier unavailable, have opened up to
      understand the genetic organization of V. cholerae. In the present study, we
      analyzed all the pathogenic non-horizontally transferred genes of V. cholerae to
      know the ancestral relationship and how the pathogenic genes have been evolved in
      V. cholerae genome. We observed that protein domain has important role in
      developing pathogenicity, and codon usage pattern of the pathogenic protein
      domain is also subject to selection. The present study unambiguously depict that
      the patterns of synonymous codon usage within a protein domain can change
      dramatically during the course of evolution to give rise to pathogenicity.

PMID- 19159614
TI  - Silencing of VAMP3 inhibits cell migration and integrin-mediated adhesion.
AB  - Integrins are transmembrane receptors for cell adhesion to the extracellular
      matrix. In cell migration, integrins are endocytosed from the plasma membrane or
      the cell surface, transported in vesicles and exocytosed actively at the cell
      front. In the present study, we examined the roles of VAMP3, a SNARE protein that
      mediates exocytosis, in cell migration and integrin trafficking. Small
      interfering RNA (siRNA)-induced silencing of VAMP3 inhibited chemotactic cell
      migration by more than 60% without affecting cell proliferation. VAMP3 silencing
      reduced the levels of beta1 integrin at the cell surface but had no effect on
      total cellular beta1 integrin, indicating that VAMP3 is required for trafficking
      of beta1 integrin to the plasma membrane. Furthermore, VAMP3 silencing diminished
      cell adhesion to laminin but not to fibronectin or collagen. Taken together,
      these data suggest that VAMP3-dependent integrin trafficking is crucial in cell
      migration and cell adhesion to laminin.

PMID- 19159615
TI  - A novel carborane analog, BE360, with a carbon-containing polyhedral boron
      cluster is a new selective estrogen receptor modulator for bone.
AB  - Carboranes are a class of carbon-containing polyhedral boron-cluster compounds
      with globular geometry and hydrophobic surface that interact with hormone
      receptors. Estrogen deficiency results in marked bone loss due to increased
      osteoclastic bone resorption in females, but estrogen replacement therapy is not
      generally used for postmenopausal osteoporosis due to the risk of uterine cancer.
      We synthesized a novel carborane compound BE360 to clarify its anti-osteoporosis
      activity. BE360 showed a high binding affinity to estrogen receptors (ER),
      ERalpha and ERbeta. In ovariectomized (OVX) mice, femoral bone volume was
      markedly reduced and BE360 dose-dependently restored bone loss in OVX mice.
      However, BE360 did not exhibit any estrogenic activity in the uterus. BE360 also
      restored bone loss in orchidectomized mice without androgenic action in the sex
      organs. Therefore, BE360 is a novel selective estrogen receptor modulator (SERM)
      that may offer a new therapy option for osteoporosis.

PMID- 19159616
TI  - Prostate specific antigen: one out of five disulfide bridges determines
      inactivation by reduction.
AB  - PSA (kallikrein hK3) proteolytic activity proved highly sensitive to reducing
      agents like dithiothreitol (DTT) and dihydrolipoic acid while beta
      mercaptoethanol and glutathione were less effective. Ascorbate exhibited no
      significant inhibitory potential. Loss of activity by reduction could be readily
      reversed by re-oxidation. Inactivation was associated with the reduction of two
      out of five conserved disulfides. Mass spectrometry of differentially modified
      cysteines, and Edman degradation analyses identified Cys 22-Cys 157 and Cys 191
      Cys 220 as DDT-sensitive. The highly homologous porcine pancreatic kallikrein
      (pK1) showed a completely different response: Even at 20 mM DDT, no inactivation
      was seen; and in this case, only one of the five disulfides (Cys 22-Cys 157) was
      opened. This indicated that it is the accessabilty of the Cys 191-Cys 220
      disulfide near the catalytic serine 195 that decides on the ability of reductants
      to inactivate the proteolytic activity of PSA. A structural basis for this
      interpretation is provided when the two homologous proteins were compared with
      respect to the threedimensional architecture around the crucial disulfide Cys 191
      Cys 220 where in the case of PK1, but not in PSA, the phenylalanine-residue (Phe
      149) is in an interfering position.

PMID- 19159617
TI  - Role of E-cadherin N-glycosylation profile in a mammary tumor model.
AB  - Modifications in cell surface glycosylation affecting cell adhesion are common
      characteristics of transformed cells. This study characterizes the N
      glycosylation profile of E-cadherin in models of canine mammary gland adenoma and
      carcinoma evaluating the importance of these glycosylation modifications in the
      malignant phenotype. Our results show that the pattern of E-cadherin N
      glycosylation in mammary carcinoma is characterized by highly branched N-glycans,
      increase in sialylation and an expression of few high mannose structures.
      Detailed mass spectrometry analysis demonstrated a new N-glycosylation site
      containing a potential complex type N-glycan in E-cadherin from a mammary
      carcinoma cell line. Our study demonstrates the importance of E-cadherin N
      glycans in the process of tumor development and in the transformation to the
      malignant phenotype.

PMID- 19159618
TI  - Preferential binding of apolipoprotein E derived peptides with oxidized
      phospholipid.
AB  - The physiological function of apolipoprotein E (apoE) includes transport and
      metabolism of lipids and its C-terminal domain harbors high affinity lipid
      binding sites. Although the binding of apoE with non-oxidized phospholipid
      containing membranes has been characterized earlier, the interaction of apoE or
      its fragments with oxidized phospholipid containing membrane has never been
      studied. In this study we have compared the interaction of amphipathic helical
      peptide sequences derived from the C-terminal domain of apoE with membrane
      vesicles containing oxidized phospholipid, 1-palmitoyl-2-azelaoyl-sn-glycero-3
      phosphocholine (PazePC), with membrane vesicles without PazePC. The interaction
      was studied by monitoring (a) fluorescence emission maxima of the peptides, (b)
      acrylamide quenching of the peptides tryptophan residues and (c) by measuring the
      equilibrium binding constants by resonance energy transfer (RET) analysis. Our
      result shows that peptide sequence 202-223, 245-266 and 268-289 of apoE has
      higher affinity towards membrane containing PazePC, compared to membrane without
      PazePC. Presence of 1mM divalent cation or 50 mM NaCl in the buffer decreased the
      binding of peptides to PazePC containing membrane vesicles suggesting possible
      involvement of the electrostatic interaction in the binding. These observations
      suggest that the preferential binding of apoE to oxidized phospholipid containing
      membrane may play a role in the anti-oxidative properties of apoE.

PMID- 19159620
TI  - Influence of pH on the reactivity of diphenyl ditelluride with thiols and anti
      oxidant potential in rat brain.
AB  - Thiol oxidation by diphenyl ditelluride is a favorable reaction and may be
      responsible for alteration in regulatory or signaling pathways. We have measured
      rate constants for reactions of diphenyl ditelluride with cysteine,
      dimercaptosuccinic acid, glutathione and dithiothreitol in phosphate buffer. The
      relative reactivities of the different thiols with diphenyl ditelluride were
      independent of the pK(a) of the thiol group, such that at pH 7.4, cysteine and
      dithiothreitol were the most reactive and low reactivity was observed with
      glutathione and dimercaptosuccinic acid. The reactivity of diphenyl ditelluride
      was not modified by change in pH. Rate of oxidation increased with increasing pH
      for all thiols except dimercaptosuccinic acid, where the rate of oxidation was
      faster at low pH. The lipid peroxidation product malonaldehyde (MDA) was measured
      in rat brain homogenate and phospholipids extract from egg yolk after incubation
      in phosphate buffer at various pHs ranging from 7.4 to 5.4. TBARS production
      increased when homogenates were incubated in the pH (5.4-6.8) medium both in the
      absence and presence of Fe(II). These data indicate that lipid peroxidation
      processes, mediated by iron, are enhanced with decreasing pH. The iron
      mobilization may come from reserves where it is weakly bound. Diphenyl
      ditelluride significantly protected TBARS production at all studied pH values in
      a concentration dependent manner in brain homogenate. This study provides in
      vitro evidence for acidosis induced oxidative stress and anti-oxidant action of
      diphenyl ditelluride.

PMID- 19159619
TI  - Anti-NF-kappaB and anti-inflammatory activities of synthetic isothiocyanates:
      effect of chemical structures and cellular signaling.
AB  - Many cancer chemopreventive agents have been associated with lower cancer risk by
      suppressing nuclear factor-kappaB (NF-kappaB) signaling pathways, which
      subsequently leads to attenuated pro-inflammatory mediators and activities. Of
      the natural compounds, the isothiocyanates (ITCs) found in cruciferous vegetables
      have received particular attention because of their potential anti-cancer
      effects. However, limited studies regarding the influence of ITCs structure on NF
      kappaB transactivation and anti-inflammatory action are reported. In the present
      study, the anti-inflammatory potential of ten structurally divergent synthetic
      ITCs were evaluated in HT-29-N9 human colon cancer cells and RAW 264.7 murine
      macrophages. The effect of ITCs on the basal transcriptional activation of NF
      kappaB and the inflammatory response to bacterial lipopolysaccharide (LPS) were
      assessed. The synthetic ITC analogs suppressed NF-kappaB-mediated pro
      inflammatory gene transcription. Among the ITC analogs, tetrahydrofurfuryl
      isothiocyanate, methyl-3-isothiocyanatopropionate, 3-morpholinopropyl
      isothiocyanate and 3,4-methyelendioxybenzyl isothiocyanate showed stronger NF
      kappaB inhibition as compared to the parent compound, phenylethyl isothiocyanate
      (PEITC). Molecular analysis revealed that several of the pro-inflammatory
      mediators and cytokines (iNOS, COX-2, IL-1beta, IL-6 and TNF-alpha) were reduced
      by ITCs, and correlated with the downregulation of NF-kappaB signaling pathways.
      Immunoblotting showed that ITCs suppressed LPS-induced phosphorylation and
      degradation of IkappaB alpha and decreased nuclear translocation of p65. In
      parallel, ITCs suppressed the phosphorylation of IkappaB kinase alpha/beta
      (IKKalpha/beta). Taken together, our findings provide the possibility that
      synthetic ITC analogs might have promising cancer chemopreventive potential,
      based on their stronger anti-NF-kappaB and anti-inflammatory activities, than the
      natural ITCs.

PMID- 19159621
TI  - Combination treatment with arsenic trioxide and irradiation enhances apoptotic
      effects in U937 cells through increased mitotic arrest and ROS generation.
AB  - Arsenic compounds have been used as anti-cancer agents in traditional Chinese
      medicine. Ionizing radiation (IR) is one of the most effective tools in the
      clinical treatment of cancer. The induction of apoptotic cell death is a
      significant mechanism of tumor cells under the influence of radio-/chemotherapy,
      and resistance to these treatments has been linked to some cancer cell lines with
      a low propensity for apoptosis. A combination of different anti-tumoral treatment
      modalities is advantageous in limiting non-specific toxicity often observed by an
      exceedingly high dose of single regimen. The present study aimed at investigating
      the enhanced effects and mechanisms in cell cycle distribution and apoptosis of
      U937 cells, a human pre-monocytic leukemia cell line lacking functional p53
      protein, after combination treatment with irradiation and As(2)O(3). Our results
      indicated that combined treatment led to activation of cdc-2, which is related to
      the expression of cyclin B. In addition, combined treatment increased apoptotic
      cell death in U937 cells, which is correlated with the induction of mitotic
      arrest, the increase in intracellular reactive oxygen species (ROS) generation,
      the decrease in B-cell leukemia/lymphoma 2 (Bcl-2) and B-cell leukemia/lymphoma
      XL (Bcl-XL) levels, the loss of mitochondria membrane potential, and the
      activation of caspase-3. We found that combining radiation and As(2)O(3) may be
      an effective strategy against p53-deficient leukemia cells.

PMID- 19159623
TI  - Effect of cholesterol or cholesteryl conjugates on the cryosurvival of bull
      sperm.
AB  - Different cholesterol conjugates-loaded-cyclodextrin was added to bull sperm to
      improve sperm quality after freezing. Ejaculates from four bulls were diluted to
      120 million cells/ml in Tris (T) diluent and then sub-divided into 10 treatments
      as follow: no additive (control); 1.5mg CLC (positive control); 0.75 mg or 1.5mg
      of cyclodextrin pre-loaded with cholesterol conjugated to heptanoate, palmitate,
      pelargonate or stearate, and incubated for 15 min at 22 degrees C. The samples
      were then diluted 1:1 with 20% egg yolk (EY) in T diluent and cooled to 5 degrees
      C over a 2h. Upon reaching 5 degrees C, the samples were diluted 1:1 with T
      diluent containing 10% EY+16% glycerol, and allowed to equilibrate for 15 min,
      and packaged into 0.5 ml straws and frozen in static liquid nitrogen vapor for 20
      min before being plunged into liquid nitrogen for storage. Straws were thawed and
      the sperm motility, viability and number sperm binding to perivitelline membrane
      were determined. The ability of bull sperm to bind to the oocyte membranes was
      conducted using the chicken egg perivitelline membrane (CEPM) as described by
      Barbato et al. [G.F. Barbato, P.G. Cramer, R.H. Hammerstedt, A practical in vitro
      sperm-egg binding assay that detects subfertile males. Biol. Reprod. 58 (1998)
      686-699] and modified by Amorim et al. [E. Amorim, J.K. Graham, B. Spizziri, M.
      Meyers, L. Amorim, C. Torres, The effect of adding cholesteryl-heptanoate, 
      palmitate, -pelargonate, or -stearate loaded cyclodextrin on bull sperm
      cryosurvival, in: Proceeding 40th Annual Meeting of the Society for the Study of
      Reproduction (SSR), July, San Antonio, TX, EUA, 2007], where these authors did
      not observe difference between bovine zona pellucide and CEPM. Higher percentages
      of motile and viable sperm were maintained after thawing from bull sperm treated
      with CLC and pelargonate compared to all other treatments (P<0.05). Control
      samples and sperm treated with heptanoate, palmitate, or stearate loaded
      cyclodextrin exhibited similar motility percentages and viable sperm after
      freezing (P>0.05). The percentage of motile sperm and number sperm binding to
      chicken egg perivitelline membrane was higher for CLC and pelargonate compared to
      control (P<0.05). Therefore, adding either cholesterol or pelargonate to bull
      sperm membranes improved cell cryosurvival, whereas treatments with cyclodextrins
      pre-loaded with other cholesterol-like molecules did not.

PMID- 19159622
TI  - The apolipoprotein A5 -1131T>C promoter polymorphism in Koreans: association with
      plasma APOA5 and serum triglyceride concentrations, LDL particle size and
      coronary artery disease.
AB  - BACKGROUND: The association between -1131T>C single nucleotide polymorphism (SNP)
      of the apolipoprotein A5 gene (APOA5) and hypertriglyceridemia raised the
      possibility that this SNP could be related to coronary artery disease (CAD) risk.
      Therefore, we investigated the association of this APOA5 -1131T>C SNP with
      circulating concentrations of APOA5, triglyceride and CAD in Koreans. METHODS:
      CAD patients (n=741) and age-, sex-matched healthy controls (n=741) were
      genotyped for the APOA5 -1131T>C SNP. The main outcome measures were the odds
      ratio (OR) on CAD risk and lipid variables, APOA5 concentration and LDL particle
      size. RESULTS: The presence of the minor allele at the -1131T>C SNP was
      associated with an increased risk of CAD [OR 1.34 (95% CI, 1.09-1.65), P=0.007]
      after adjusting for BMI, alcohol consumption, systolic blood pressure and
      diastolic blood pressure. There was an association between the APOA5
      concentration and the -1131T>C genotype in controls (T/T: 245+/-7 ng/ml, T/C:
      220+/-6, C/C: 195+/-12; P=0.001) and CAD patients (T/T: 218+/-8 ng/ml, T/C: 185+/
      7, C/C: 169+/-12; P<0.001). Subjects with T/C or C/C in control and CAD patient
      groups showed higher triglyceride than those with T/T genotype. Also, the 
      1131T>C polymorphism was associated with LDL particle size (P=0.003), with the
      T/C or C/C controls having smaller size than the T/T controls. CONCLUSIONS: The
      APOA5 -1131C allele is associated with reduced APOA5 concentration and with
      increased CAD risk. This is consistent with the observed association between the 
      1131C SNP, increased triglycerides as well as small LDL particle size.

PMID- 19159624
TI  - Identification of an ancient Bmp4 mesoderm enhancer located 46 kb from the
      promoter.
AB  - Bone morphogenetic protein 4 (Bmp4) is a multi-functional, developmentally
      regulated gene that is essential for mouse development, as most Bmp4-null mouse
      embryos die at the onset of gastrulation and fail to develop mesoderm. Little is
      known about the transcriptional regulation of Bmp4. To identify potential long
      range cis-regulatory elements that direct its complex spatiotemporal expression
      patterns, we surveyed the mouse Bmp4 locus using two overlapping bacterial
      artificial chromosome (BAC) reporter transgenes. Our findings indicate that
      tissue-specific cis-regulatory elements reside greater than 28 kb 5' or 3' to the
      mouse Bmp4 transcription unit. In addition, comparative analyses identified three
      noncoding evolutionarily conserved regions (ECRs), spaced around the gene and
      conserved from mammals to fish, that are maintained in a syntenic group across
      vertebrates. Deletion of one of these conserved sequences (ECR2) from a BAC
      transgene revealed a tissue-specific requirement for ECR2 in driving Bmp4
      expression in extraembryonic and embryonic mesoderm. Furthermore, a 467 bp mouse
      sequence containing ECR2 reproducibly directed lacZ minigene expression in
      mesoderm. Taken together, this shows that an ancient, mesoderm-specific cis
      regulatory element resides nearly 50 kb 5' to mouse Bmp4.

PMID- 19159625
TI  - Mesenchymal stem cells expressing neural antigens instruct a neurogenic cell fate
      on neural stem cells.
AB  - The neurogenic response to injury in the postnatal brain is limited and
      insufficient for restoration of function. Recent evidence suggests that
      transplantation of mesenchymal stem cells (MSCs) into the injured brain is
      associated with improved functional recovery, mediated in part through
      amplification in the endogenous neurogenic response to injury. In the current
      study we investigate the interactions between bone marrow-derived MSCs and
      embryonic neural stem cells (NSCs) plus their differentiated progeny using an in
      vitro co-culture system. Two populations of MSCs were used, MSCs induced to
      express neural antigens (nestin+, Tuj-1+, GFAP+) and neural antigen negative
      MSCs. Following co-culture of induced MSCs with differentiating NSC/progenitor
      cells a significant increase in Tuj-1+ neurons was detected compared to co
      cultures of non-induced MSCs in which an increase in astrocyte (GFAP+)
      differentiation was observed. The effect was mediated by soluble interactions
      between the two cell populations and was independent of any effect on cell death
      and proliferation. Induced and non-induced MSCs also promoted the survival of Tuj
      1+ cell progeny in long-term cultures and both promoted axonal growth, an effect
      also seen in differentiating neuroblastoma cells. Therefore, MSCs provide
      instructive signals that are able to direct the differentiation of NSCs and
      promote axonal development in neuronal progeny. The data indicates that the
      nature of MSC derived signals is dependent not only on their microenvironment but
      on the developmental status of the MSCs. Pre-manipulation of MSCs prior to
      transplantation in vivo may be an effective means of enhancing the endogenous
      neurogenic response to injury.

PMID- 19159626
TI  - Phylogenic analysis of the genus Leishmania by cytochrome b gene sequencing.
AB  - In a previous report (Luyo-Acero et al., 2004), we demonstrated that cytochrome b
      (Cyt b) gene analysis is an effective method for classifying several isolates of
      the genus Leishmania; hence, we have further applied this method to other
      Leishmania species in an effort to enhance the accuracy of the procedure and to
      construct a new phylogenic tree. In this study, a total of 30 Leishmania and
      Endotrypanum WHO reference strains, clinical isolates from our patients assigned
      to 28 strains (human and non-human pathogenic species) and two species of the
      genus Endotrypanum were analyzed. The Cyt b gene in each sample was amplified by
      PCR, and was then sequenced by several primers, as reported previously. The
      phylogenic tree was constructed based on the results obtained by the computer
      software MEGA v3.1 and PAUP* v4.0 Beta. The present phylogenic tree was almost
      identical to the traditional method of classification proposed by Lainson and
      Shaw (1987). However, it produces the following suggestions: (1) exclusion of L.
      (Leishmania) major from the L. (L.) tropica complex; (2) placement of
      L.tarentolae in the genus Sauroleishmania; (3) L. (L.) hertigi complex and L.
      (V.) equatorensis close to the genus Endotrypanum; (4) L. (L.) enrietti, defined
      as L. (L.) mexicana complex, placed in another position; and (5) L. (L.) turanica
      and L. (L.) arabica are located in an area far from human pathogenic Leishmania
      strains. Cyt b gene analysis is thus applicable to the analyzing phylogeny of the
      genus Leishmania and may be useful for separating non-human pathogenic species
      from human pathogenic species.

PMID- 19159627
TI  - Development of a multiplexed fluorescent immunoassay for the quantitation of
      antibody responses to four Neisseria meningitidis serogroups.
AB  - Neisseria meningitidis is a gram-negative bacterium causing disease world wide
      with a fatality rate of 5-10%. Five serogroups, A, B, C, Y and W-135 are
      responsible for virtually all cases of the disease in humans. We have developed a
      multiplexed assay for the simultaneous quantitation of IgG antibody responses to
      the four most immunogenic (A, C, Y, and W-135) N. meningitidis serogroups. A
      simple and less manipulative method was employed for conjugation of the capsular
      polysaccharide antigens to the microspheres. The multiplex assay compared well
      with traditional individual ELISAs, but demonstrated greater than 1 log increase
      in dynamic range and sensitivity. Specificity studies of the multiplex assay
      showed greater than 95% homologous inhibition and less than 5% heterologous
      inhibition for all four serogroups. Intra and inter-assay CVs were generally less
      than 10% and the limit of detection was <600 pg/ml. The multiplexed assay proved
      to be reproducible as well as specific and sensitive when compared to the
      standardized ELISAs. Advantages included a greater dynamic range and simultaneous
      detection of antibody responses to the four serogroups contained in the
      tetravalent meningococcal polysaccharide vaccine.

PMID- 19159628
TI  - Pressure-overload magnitude-dependence of the anti-hypertrophic efficacy of PDE5A
      inhibition.
AB  - Increased myocardial cGMP, achieved by enhancing cyclase activity or impeding
      cGMP hydrolysis by phosphodiesterase type-5 (PDE5A), suppresses cellular and
      whole organ hypertrophy. The efficacy of the latter also requires cyclase
      stimulation and may depend upon co-activation of maladaptive signaling
      suppressible by cGMP-stimulated kinase (cGK-1). Thus, PDE5A inhibitors could
      paradoxically be more effective against higher than lower magnitudes of pressure
      overload stress. To test this, mice were subjected to severe or moderate trans
      aortic constriction (sTAC, mTAC) for 6 wks +/-co-treatment with oral sildenafil
      (SIL 200 mg/kg/d). LV mass (LVM) rose 130% after 3-wks sTAC and SIL blunted this
      by 50%. With mTAC, LVM rose 56% at 3 wks but was unaffected by SIL, whereas a 90%
      increase in LVM after 6 wks was suppressed by SIL. SIL minimally altered LV
      function and remodeling with mTAC until later stages that stimulated more
      hypertrophy and remodeling. SIL stimulated cGK-1 activity similarly at 3 and 6
      wks of mTAC. However, pathologic stress signaling (e.g. calcineurin, ERK
      MAPkinase) was little activated after 3-wk mTAC, unlike sTAC or later stage mTAC
      when activity increased and SIL suppressed it. With modest hypertrophy (3-wk
      mTAC), GSK3beta and Akt phosphorylation were unaltered but SIL enhanced it.
      However, with more severe hypertrophy (6-wk mTAC and 3-wk sTAC), both kinases
      were highly phosphorylated and SIL treatment reduced it. Thus, PDE5A-inhibition
      counters cardiac pressure-overload stress remodeling more effectively at higher
      than lower magnitude stress, coupled to pathologic signaling activation
      targetable by cGK-1 stimulation. Such regulation could impact responses of
      varying disease models to PDE5A inhibitors.

PMID- 19159629
TI  - N-acetylcysteine prevents glucose/glucose oxidase-induced oxidative stress,
      mitochondrial damage and apoptosis in H9c2 cells.
AB  - AIMS: High blood glucose may auto-oxidize and generate free radicals, which are
      proposed to induce apoptosis in cardiac cells. The aim of the present study was
      to investigate the cell damage induced by glucose/glucose oxidase-dependent
      oxidative stress and the protective effect of N-acetylcysteine (NAC) on H9c2
      cardiac muscle cells. MAIN METHODS: H9c2 cells were exposed to 33 mM glucose
      (G)+1.6 milliunits (mU) of glucose oxidase (GO) and termed G/GO. Cell apoptosis,
      generation of reactive oxygen species (ROS-super oxide anion and hydrogen
      peroxide) and reactive nitrogen species (RNS-peroxinitrite), and the change in
      mitochondrial membrane potential (DeltaPsim) was studied using flow cytometry and
      confocal microscopy, and cytochrome c release was measured using confocal
      microscopy. The expression of Bcl-2, Bax and the activation of procaspase-9 was
      studied by western blot. KEY FINDINGS: Exposure of H9c2 cells to G/GO resulted in
      a significant increase in cellular apoptosis (P<0.05) and the generation of ROS
      and RNS (P<0.001). Further, G/GO treatment led to a decrease in DeltaPsim,
      release of cytochrome c, decrease in Bcl-2, increase in Bax expression and the
      activation of procaspase-9. Treatment with NAC significantly decreased apoptosis
      (P<0.05) and reduced the levels of ROS and RNS (P<0.001). NAC was also able to
      normalize DeltaPsim, inhibit cytochrome c release, increase Bcl-2 and decrease
      Bax expression and procaspase-9 activation. SIGNIFICANCE: Our studies suggest
      that NAC has antioxidative and antiapoptotic activity against G/GO-induced
      oxidative stress through the inhibition of mitochondrial damage in H9c2 cells.

PMID- 19159630
TI  - Possible involvement of activation of P53/P21 and demethylation of RUNX 3 in the
      cytotoxicity against Lovo cells induced by 5-Aza-2'-deoxycytidine.
AB  - AIMS: In our model, we aimed to explore the cytotoxicity of 5-Aza-2'
      deoxycytidine (5-Aza-CdR) against the colorectal cell line, Lovo, and further
      characterize the possible mechanisms. MAIN METHODS: After Lovo cells were treated
      with 5-Aza-CdR at different concentrations for different periods of time, the
      cell viability was examined using an MTT assay and apoptosis was examined using
      both flow cytometry and DNA laddering. To examine the mechanisms by which Lovo
      cells respond to 5-Aza-CdR, we measured both caspase 3 activity as well as DNA
      damage. Western blotting and RT-PCR assays were used to assess the changes in the
      expression levels of P53, P21(Waf1/Cip1), runt-related transcription factor 3
      (RUNX 3), DNA methyltransferases (DNMTs) and matrix metalloproteinases (MMPs).
      Additionally, we performed gelatin zymography to examine the effects of 5-Aza-CdR
      on metastasis. KEY FINDINGS: We observed that the growth and survival advantages
      of Lovo cells were overcome with 5-Aza-CdR treatment at limited concentrations.
      Mechanistic exploration demonstrated that 5-Aza-CdR was incorporated into the DNA
      to induce DNA damage in Lovo cells, which was evidenced by activation of P53,
      P21(Waf1/Cip1) and a caspase-independent cell apoptosis pathway. Also, further
      experiments preliminarily suggested that 5-Aza-CdR results in the deletion of
      DNMT 3a and DNMT 3b, but not DNMT 1, which reactivates the expression of RUNX 3.
      Finally, our data revealed that 5-Aza-CdR potentially reduces the activity and
      expression of MMP 2. SIGNIFICANCE: These data greatly enhance our understanding
      of how human cancer cells respond to 5-Aza-CdR and also reveal a new role for 5
      Aza-CdR in improving patient outcome in human colorectal cancer.

PMID- 19159631
TI  - Predicting metapopulation lifetime from macroscopic network properties.
AB  - This paper presents a comparatively simple approximation formula for the mean
      life time of a metapopulation in a habitat network where habitat patch
      arrangement may be irregular and patch sizes differ. It is based on previous work
      on the development of an analytical approximation formula by Frank and Wissel [K.
      Frank, C. Wissel, A formula for the mean lifetime of metapopulations in
      heterogeneous landscapes, Am. Nat. 159 (2002) 530] and extends it by abstracting
      from individual patch locations. The mean metapopulation lifetime is expressed as
      a function of four macroscopic network properties: the ratio of dispersal range
      and network size, the ratio of range of environmental correlation and network
      size, and the total number and (geometric mean) size of the patches. The analysis
      takes into account that (ceteris paribus) patches close to the boundary of the
      habitat network contribute less to metapopulation survival than patches close to
      the centre of the network. Ignoring this fact can lead to a substantial
      overestimation of the mean metapopulation lifetime. Due to its numerical
      simplicity, the formula can be used as a conservation objective function even in
      complex network design problems where the number of patches to be allocated is
      very large. Numerical tests of the formula show that it performs very well within
      a wide range of network structures.

PMID- 19159632
TI  - Effects of vitamin C on hyperoxia-induced reduction of retinal blood flow.
AB  - OBJECTIVE: Breathing of 100% oxygen causes vasoconstriction in retinal vessels
      paralleled by a decrease in blood flow. The mechanism underlying this effect is
      still unclear, but may be related to the increased generation of reactive oxygen
      species during hyperoxia. Thus, the purpose of the present study was to
      investigate whether vitamin C, an agent with strong antioxidative properties,
      modifies the retinal vasoconstrictor response to hyperoxia. METHODS: A
      randomized, double-masked, placebo controlled, two-way crossover study was
      performed in 12 healthy young volunteers. 100% oxygen was administered via a
      breathing mask for 12 min. Retinal blood flow was measured before and during
      oxygen breathing in the presence of either ascorbic acid (3 g) or placebo on two
      different study days. Retinal blood flow was determined based on measurement of
      retinal vessel diameters and red blood cell velocity. RESULTS: Breathing of 100%
      oxygen induced a pronounced reduction of retinal arterial (-7.6%+/-6.5%) and
      venous diameters (-12%+/-6%). Hyperoxia induced vasoconstriction was not altered
      by co-administration of vitamin C (-8.6%+/-4.8% in arteries and -15%+/-7% in
      veins). Likewise, RBV and retinal blood flow decreased in response to oxygen by 
      24%+/-53% and -38%+/-42%. Again, the reduction of retinal hemodynamic parameters
      was not altered by co-administration of vitamin C. CONCLUSIONS: Oxygen induced
      blood flow response in the human retina is not altered by a single dose of
      vitamin C in healthy, young subjects. Whether this indicates that ROS are not
      involved in hyperoxia induced vasoconstriction of retinal vessels or is related
      to other factors has yet to be determined.

PMID- 19159633
TI  - Berberine induces p53-dependent cell cycle arrest and apoptosis of human
      osteosarcoma cells by inflicting DNA damage.
AB  - Alkaloid berberine is widely used for the treatment of diarrhea and other
      diseases. Many laboratory studies showed that it exhibits anti-proliferative
      activity against a wide spectrum of cancer cells in culture. In this report we
      studied the mechanisms underlying the inhibitory effects of berberine on human
      osteosarcoma cells and on normal osteoblasts. The inhibition was largely
      attributed to cell cycle arrest at G1 and G2/M, and to a less extent, to
      apoptosis. The G1 arrest was dependent on p53, as G1 arrest was abolished in p53
      deficient osteosarcoma cells. The induction of G1 arrest and apoptosis was
      accompanied by a p53-dependent up-regulation of p21 and pro-apoptotic genes.
      However, the G2/M arrest could be induced by berberine regardless of the status
      of p53. Interestingly, DNA double-strand breaks, as measured by the
      phosphorylation of H2AX, were remarkably accumulated in berberine-treated cells
      in a dose-dependent manner. Thus, one major mechanism by which berberine exerts
      its growth-inhibitory effect is to inflict genomic lesions on cells, which in
      turn trigger the activation of p53 and the p53-dependent cellular responses
      including cell cycle arrest and apoptosis.

PMID- 19159634
TI  - Laboratory-based and autobiographical retrieval tasks differ substantially in
      their neural substrates.
AB  - In designing experiments to investigate retrieval of event memory, researchers
      choose between utilizing laboratory-based methods (in which to-be-remembered
      materials are presented to participants) and autobiographical approaches (in
      which the to-be-remembered materials are events from the participant's pre
      experimental life). In practice, most laboratory studies have utilized old/new
      recognition memory, and most autobiographical memory studies have used the Galton
      Crovitz word cueing technique [Crovitz, H.F., & Schiffman, H. (1974). Frequency
      of episodic memories as a function of their age. Bulletin of the Psychonomic
      Society, 4, 517-518]. What are the implications of these methodological choices
      for understanding the component processes and underlying neural substrates of
      memory retrieval? An Activation Likelihood Estimation (ALE) meta-analysis
      procedure [Turkeltaub, P., Eden, G., Jones, K., & Zeffiro, TA. (2002). Meta
      analysis of the functional neuroanatomy of single-word reading: Method and
      validation. NeuroImage, 16, 765-780] was used to construct two whole-brain
      statistical maps: one showing brain regions that are consistently implicated when
      the task utilized is old/new recognition memory and one showing regions that tend
      to emerge when autobiographical event memory is queried. A comparison of the two
      maps shows very few regions of overlap. This basic methodological choice has a
      profound impact on the conclusions reached regarding human memory retrieval and
      its neural substrates.

PMID- 19159635
TI  - Immediate and delayed actions share a common visuomotor transformation mechanism:
      a prism adaptation study.
AB  - It is a key assumption of the perception/action model that the dorsal stream
      relies on current visual input and does not store visual information over an
      extended period of time. Consequently, it is expected that action which is guided
      by memorized visual information, so-called delayed action, cannot use information
      from the dorsal stream but must rely instead on the ventral stream input.
      However, it is currently unclear how the information from the ventral stream can
      be used to guide an action. This issue is particularly challenging given that the
      perception/action model also assumes that ventral stream input is not
      particularly useful for guiding actions since the information it provides is
      coded relative to the visual scene and not relative to the observer. We describe
      two possible solutions to this problem and suggest that they can be tested using
      the prism adaptation paradigm. Subjects in our study were adapted to optical
      prisms using either an immediate or a delayed pointing task. In both cases,
      subjects showed the typical post-exposure negative aftereffect. Moreover, there
      was almost complete transfer of the aftereffect between immediate and delayed
      pointing. This is particularly surprising given the long history of findings
      showing little transfer between motor tasks for which separate neural
      representations are assumed. In this context our findings suggest a substantial
      overlap in the visuomotor transformation processes used for immediate and delayed
      pointing.

PMID- 19159636
TI  - Is family special to the brain? An event-related fMRI study of familiar,
      familial, and self-face recognition.
AB  - The face-processing network has evolved to respond differentially to different
      classes of faces depending on their relevance to the perceiver. For example, self
      , familiar, and unknown faces are associated with activation in different neural
      substrates. Family should represent a special class of face stimuli that is of
      high relevance to individuals, because incorrect assignment of kinship can have
      dire consequences (e.g., incest, cuckoldry). Therefore evolution should have
      favored redundant mechanisms for detection of kin. We used fMRI to investigate
      the neural substrates associated with viewing faces of kin compared to other
      classes of faces (e.g., self-face, familiar face, and unknown face), and to
      examine the degree to which self-facial resemblance activated similar neural
      substrates. Contrasting kin faces with unknown faces activated substrates
      associated with self-face recognition, while comparing kin faces to friend faces
      activated posterior cingulate and cuneus. Similar posterior medial substrates
      were recruited when contrasting self-resembling faces with morphed faces of kin,
      suggesting these regions potentially represent computational processing about
      facial familiarity and identity. On the other hand, discrimination of self
      resembling faces from familiar morphs activated anterior medial substrates
      (anterior cingulate cortex, ACC, medial prefrontal cortex, MPFC). These findings,
      and a region of interest (ROI) analysis, highlight the role of the extended face
      processing network for discrimination of kin from familiar non-kin members of
      one's social group based on self-referent phenotypic cues.

PMID- 19159637
TI  - Early non-visual experience influences proprioceptive-spatial discrimination
      acuity in adulthood.
AB  - The present study tested whether non-visual spatial experience affects later
      acuity of space perception. Congenitally blind adults who differed in the age
      acquired spatial knowledge via an orientation and mobility (O&M) training and
      matched sighted controls performed passive arm movements and judged the direction
      of the sensed movement. Proprioceptive-spatial discrimination acuity was assessed
      by an adaptive psychophysical procedure in two spatial coding conditions. In the
      egocentric coding condition, participants judged whether the hand trajectory felt
      left- or right-tilted in reference to a straight trajectory aligned to the
      transverse horizontal plane of the body midline axis. In the allocentric coding
      condition, they indicated whether the hand trajectory felt acute- or obtuse
      angled in reference to a right angle. Proprioceptive-spatial acuity of
      congenitally blind participants significantly covaried with the age they attended
      an O&M training. The earlier the congenitally blind participants started the O&M
      training the more accurate was their space perception. Congenitally blind
      participants who underwent an O&M training after the age of 12 years showed
      poorer acuity than sighted controls. Congenitally blind participants with an
      earlier O&M training, however, approached the performance level of the sighted
      controls. The observed improvement in spatial acuity was more pronounced when
      judgements were given on the basis of an allocentric than an egocentric frame of
      reference. These findings suggest that proprioceptive-spatial acuity in adulthood
      depends on non-visual spatial experience during early development.

PMID- 19159638
TI  - Electrophysiological correlates of improved short-term memory for emotional
      faces.
AB  - Long-term memory (LTM) is enhanced for emotional information, but the influence
      of stimulus emotionality on short-term memory (STM) is less clear. We examined
      the electrophysiological correlates of improved visual STM for emotional face
      identity, focusing on the P1, N170, P3b and N250r event-related potential (ERP)
      components. These correlates are taken to indicate which memory processing stages
      and cognitive processes contribute to the improved STM for emotional face
      identity. In the encoding phase, one or three angry, happy or neutral faces were
      presented for 2s, resulting in a memory load of one or three. The subsequent 1-s
      retention phase was followed by a 2-s retrieval phase, in which participants
      indicated whether a probe face had been present or not during encoding. Memory
      performance was superior for angry and happy faces over neutral faces at load
      three. None of the ERP components during encoding were affected by facial
      expression. During retrieval, the early P3b was decreased for emotional compared
      to neutral faces, which presumably reflects greater resource allocation to the
      maintenance of the emotional faces. Furthermore, the N250r during retrieval was
      increased for emotional compared to neutral faces, reflecting an enhanced
      repetition effect for emotional faces. These findings suggest that enhanced
      visual STM for emotional faces arises from improved maintenance and from improved
      detection of face repetition at retrieval.

PMID- 19159639
TI  - Molecular mechanisms mediating oxidative stress-induced T-cell suppression in
      cancer.

PMID- 19159640
TI  - Nuclear inositides: PI-PLC signaling in cell growth, differentiation and
      pathology.

PMID- 19159642
TI  - Hesperidin, a flavonoid glycoside with sedative effect, decreases brain pERK1/2
      levels in mice.
AB  - The aim of this work was to evaluate if the intraperitoneal administration of the
      natural compound hesperidin, in a sedative dose, and neo-hesperidin, a hesperidin
      structural analog that exerts minor sedative effect, were able to induce changes
      in intracellular signaling cascades in different areas of the brain. The systemic
      administration of hesperidin produced a marked reduction in the phosphorylation
      state of extracellular signal-regulated kinases 1/2 (ERK 1/2), but not of
      Ca(+2)/calmodulin-dependent protein kinase II alpha subunit (alphaCaMKII), in the
      cerebral cortex, cerebellum and hippocampus. In contrast, neo-hesperidin did not
      markedly affect the activity of ERK 1/2 in both the cortex and the cerebellum.
      Taken together, these results demonstrated that intracellular signalling
      involving a selective decrease in ERK1/2 activation accompanied the depressant
      action of hesperidin. Even more, the low sedative action of neo-hesperidin
      correlates with a negligible decrease in phosphorylation state of ERK 1/2 (pERK
      1/2), suggesting that low levels of pERK 1/2 in CNS could be a marker of sedative
      efficacy of flavonoids.

PMID- 19159641
TI  - iTRAQ proteomic identification of pVHL-dependent and -independent targets of
      Egln1 prolyl hydroxylase knockdown in renal carcinoma cells.

PMID- 19159643
TI  - Discriminative-stimulus and time-course effects of kava-kava (Piper methysticum)
      in rats.
AB  - Kava is a widely available and used herbal medicine that is not regulated in many
      countries. There are many questions concerning kava's stimulus properties,
      potential for therapeutic use, and potential for abuse. Although there is
      evidence that kava may possess some anxiolytic properties, kava's mechanism of
      action and the extent to which it may serve as an alternative to pharmaceutical
      anxiolytics are not fully known. The current study was designed to evaluate
      whether kava shares discriminative-stimulus properties with the anxiolytic
      chlordiazepoxide (CDP). Effects of different doses of kava extract were evaluated
      in two groups of rats trained to discriminate either a high or low training dose
      of CDP (i.p.). In order to assess time-course effects, two tests were
      conducted/session at 60 (Test One) and 90 (Test Two) min following oral
      administration of kava, CDP, or d-amphetamine. Dose-dependent substitution of CDP
      was found in both training groups in both tests. Kava (560 mg/kg, p.o.)
      occasioned responding indicative of partial substitution in both groups during
      Test One and only the low-dose group during Test Two. Partial substitution of
      kava extract for CDP suggests that the herbal compound may share a mechanism of
      action similar to CDP, but is less potent.

PMID- 19159644
TI  - Resilience and patterns of health risk behaviors in California adolescents.
AB  - OBJECTIVES: Assess whether adolescent health risk behaviors cluster, and whether
      resiliency factors are associated with observed clusters. METHODS: The cross
      sectional population-weighted 2003 California Health Interview Survey was used
      (N=4010). Four gender-specific clusters were based on smoking, alcohol use, low
      fruit/vegetables consumption, and physical inactivity. Resiliency factors
      included parental supervision, parental support, role model presence and
      adolescent mental health. Conditional regression was used to measure the
      association of individual health risk behaviors and clusters with resiliency
      factors. RESULTS: Health risk behaviors clustered as follows: "Salutary
      Adherents" (no reported health risk behaviors), "Active Snackers" (physically
      active, low fruit/vegetable consumers), "Sedentary Snackers" (physically
      inactive, low fruit/vegetable consumers), and "Risk Takers" (smokers, alcohol
      users, many also physically inactive and low fruit/vegetable consumers). Greater
      parental supervision was associated with lower odds of being in unhealthful
      clusters. Among males, having greater parental support reduced odds of being an
      "Active Snacker" or "Sedentary Snacker." Among females, role model presence
      reduced odds of being in unhealthful clusters, while depressiveness increased the
      odds. CONCLUSIONS: Health promoting interventions should address multiple health
      risk behaviors in an integrated fashion. Gender-specific, ethnically-targeted,
      family-centered strategies that address parenting, particularly parental
      supervision would be useful. Addressing depressiveness may be especially
      important for female adolescents.

PMID- 19159645
TI  - Socio-demographic variation in smoking habits: Italy, 2008.
AB  - OBJECTIVE: To provide updated information on smoking prevalence in Italy, with a
      focus on demographic and socio-economic characteristics. METHOD: The survey was
      conducted during March-April 2008 on a sample of 3035 individuals (1459 men and
      1576 women) aged 15 years or over representative of the Italian population in
      terms of age, sex, geographic area, and socio-economic characteristics. RESULTS:
      In 2008, 22.0% (95% confidence interval, CI: 20.5-23.5) of Italians described
      themselves as current cigarette smokers (26.4% of men, 17.9% of women); ex
      smokers were 18.4% (95% CI: 17.0-19.8; 24.1% of men, 13.2% of women). By the year
      2012 the number of former could exceed that of current smokers. Smoking
      prevalence in the young (15-24 years) was around 30% in males, and almost 20% in
      females. For both sexes, current smoking was less prevalent in higher (22.9% of
      men, 20.1% of women) than in lower educated participants (34.8% of men, 22.1% of
      women), and in northern (22.5% of men, 16.1% of women) than southern Italy (31.8%
      of men, 18.4% of women). CONCLUSION: In 2008, smoking prevalence was the lowest
      observed over the last 50 years, in Italy. However, part of the fall is likely
      due to increased under-reporting, since these survey figures are appreciably
      under-estimated as compared to sale data. Subjects with less privileged socio
      economic characteristics should be considered target populations for tobacco
      control.

PMID- 19159646
TI  - The Aedes aegypti cell line CCL-125 is dengue virus permissive.
AB  - While the majority of dengue infections worldwide are transmitted by the Aedes
      aegypti mosquito, the majority of research into the interaction between dengue
      and insect cells is undertaken in the Aedes albopictus derived cell line C6/36.
      The CCL-125 cell line is a long established A. aegypti derived cell line that was
      originally characterized as not susceptible to infection by the dengue virus. The
      present study establishes that CCL-125 is permissive to dengue virus infection
      and is able to be infected productively as determined by both plaque assay and
      immunocytochemistry. Infection occurred without observable cytopathic effect.
      This study demonstrates the utility of the A. aegypti derived cell line CCL-125
      as a dengue permissive cell line and suggests that it may be a useful alternative
      to C6/36 cells in dissecting out the dengue virus-insect cell interaction.

PMID- 19159647
TI  - A role for the extracellular signal-regulated kinase signal pathway in depressive
      like behavior.
AB  - Our recent research demonstrates that the extracellular signal-regulated kinase
      (ERK) signal pathway is impaired in depressed animals, and such disruption is
      effectively reversed following antidepressant treatment. These results indicate
      that the ERK pathway may participate in the molecular mechanism of depression. To
      provide direct evidence for the potential role of the ERK pathway in depression,
      the present study using a sub-chronic regimen of ERK inhibition investigated the
      disparate role for the ERK cascade in two specific brain areas, the dorsal
      hippocampus (dHP) and the medial prefrontal cortex (mPFC), in the pathophysiology
      of depressive-like behavior. Rats were bilaterally implanted with cannulas in the
      dHP or mPFC and were microinjected with U0126, a specific inhibitor of ERK
      upstream activator, or vehicle for 7 consecutive days. The behavioral effects of
      the ERK pathway inhibition were examined in the open field, elevated plus maze,
      and saccharin preference test. The results showed that the inhibition of the ERK
      pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK
      pathway inhibition in the mPFC induced anhedonia and locomotor impairment in
      rats. The phosphorylation of the cyclic AMP-responsive-element-binding protein
      (CREB) was decreased following the ERK pathway inhibition either in dHP or mPFC.
      These findings demonstrate that the ERK pathway in either the dHP or mPFC
      participates in the pathophysiology of the depressive-like behavior, and may have
      pivotal role in human depression.

PMID- 19159648
TI  - The nucleus accumbens core and shell are critical for the expression, but not the
      consolidation, of Pavlovian conditioned approach.
AB  - The nucleus accumbens (NAc) is important for the ability of motivationally
      significant stimuli to guide behavior. To further delineate its role in
      appetitive Pavlovian conditioning, we tested the hypothesis that the NAc
      contributes to memory consolidation and expression for a goal-tracking version of
      Pavlovian conditioned approach (PCA) in rats. We found that neither post-training
      reversible inactivation with the GABA receptor agonists muscimol and baclofen nor
      inhibition of protein synthesis with anisomycin (ANI) in either the core or shell
      regions of the NAc had an effect on approach to a reward port in response to a
      reward-predictive cue (conditioned stimulus, CS+). In contrast, pre-test
      reversible inactivation of both the core and shell decreased conditioned
      responding during the CS+. Unlike inactivation of the core, however, reversible
      inactivation of the shell also produced an increase in responding during the CS-
      and the inter-trial interval. This suggests that the NAc is not involved in the
      consolidation of goal-tracking PCA, but that once the memory is formed, the core
      is required for expression of the CS-unconditioned stimulus (US) association and
      the shell is required to inhibit conditioned approach behavior at times when the
      CS+ is not presented.

PMID- 19159649
TI  - Selective effect of INGAP-PP upon mouse embryonic stem cell differentiation
      toward islet cells.
AB  - We evaluated the effect of islet neogenesis-associated protein pentadecapeptide
      (INGAP-PP) upon islet beta- and non-beta cell differentiation from mouse
      embryonic stem (mES) cells. ES-D3 cell lines were cultured following Lumelsky's
      protocol with or without INGAP-PP (5 microg/ml) at different stages. Gene
      expression was quantified using qPCR. mES cells were fixed and immunostained
      using anti insulin-, somatostatin-, glucagon-, Pdx-1-, Ngn-3-, Nkx-6.1 and PGP9.5
      specific antibodies. PCNA was used to measure replication rate. Bcl(2)
      (immunostaining) and caspase-3 (enzyme activity and gene expression) were
      determined as apoptosis markers. INGAP-PP increased IAPP, Glut-2, Kir-6.2, SUR-1
      and insulin gene expression, and the percentage of insulin-immunostained cells.
      Conversely, INGAP-PP reduced significantly glucagon and somatostatin gene
      expression and immunopositivity. While nestin gene expression was not affected,
      there was a significant reduction in the percentage of PGP9.5-immunostained
      cells. Pdx-1 gene expression increased by 115% in INGAP-PP treated cells, as well
      as the percentage of Pdx-1, Ngn-3 and Nkx-6.1 immunopositive cells. Neither
      caspase-3 (expression and activity) nor Bcl(2) positively immunostained cells
      were affected by INGAP-PP. Accordingly, INGAP-PP would promote stem cell
      differentiation into a beta-like cell phenotype, simultaneously decreasing its
      differentiation toward non-beta-cell precursors. Therefore, INGAP-PP would be
      potentially useful to obtain beta-cells from stem cells for replacement therapy.

PMID- 19159650
TI  - Permeabilization and hybridization protocols for rapid detection of Bacillus
      spores using fluorescence in situ hybridization.
AB  - BACKGROUND: Fluorescence in situ hybridization (FISH) is not adapted for the
      detection of bacterial spores because of their resistance to conventional
      permeabilization treatments. Since spore-forming bacteria have important
      ecological, economical, and medical roles, their in situ detection needs to be
      improved. The aim of this study was to develop rapid and effective protocols to
      permeabilize Bacillus spores in order to apply the FISH technique. METHODS:
      Permeabilization protocols were developed for three species of Bacillus spores.
      Hybridization was performed using universal and specific probes. Surface
      structural analysis of the permeabilization treatments was performed using
      scanning electron microscopy. RESULTS: With the proposed protocols, Bacillus
      spores can be labeled in less than 1 h. The scanning microscopy showed some
      visible structural differences between the permeabilized spores compared to
      intact ones. CONCLUSION: For the first time, rapid and effective protocols to
      detect Bacillus spores by FISH were developed and can be applied to study
      Bacillus spores using in situ labeling within 1 h. Previously published in situ
      hybridization protocols have never reached or been close to the currently
      described rapidity. This work will contribute to the possibility of near real
      time detection of biological threats that may be present as spores.

PMID- 19159651
TI  - Analysis of RegA, a pathway-specific regulator of the friulimicin biosynthesis in
      Actinoplanes friuliensis.
AB  - The rare actinomycete Actinoplanes friuliensis is the producer of the lipopeptide
      antibiotic friulimicin, which is active against a broad range of Gram-positive
      bacteria such as methicillin-resistant Enterococcus spec. and Staphylococcus
      aureus (MRE, MRSA) strains. Friulimicin consists of a decapeptide core and an
      acyl residue linked to an exocyclic amino acid. The complete biosynthetic gene
      cluster consisting of 24 open reading frames was characterized by sequence
      analysis and the transcription units were subsequently determined by RT-PCR
      experiments. In addition to several genes for biosynthesis, self-resistance and
      transport four different regulatory genes (regA, regB, regC and regD) were
      identified within the cluster. To analyse the role of the pathway-specific
      regulatory protein RegA in the friulimicin biosynthesis, the corresponding gene
      was inactivated resulting in friulimicin non-producing mutants. Furthermore,
      several protein-binding sites within the friulimicin gene cluster were identified
      by gel retardation assays. By real-time RT-PCR experiments, it was shown that the
      majority of the friulimicin biosynthetic genes is positively regulated by RegA.

PMID- 19159652
TI  - Plant virus emergence and evolution: origins, new encounter scenarios, factors
      driving emergence, effects of changing world conditions, and prospects for
      control.
AB  - This review focuses on virus-plant pathosystems at the interface between managed
      and natural vegetation, and describes how rapid expansion in human activity and
      climate change are likely to impact on plants, vectors and viruses causing
      increasing instability. It starts by considering virus invasion of cultivated
      plants from their wild ancestors in the centres of plant domestication in
      different parts of the world and subsequent long distance movement away from
      these centres to other continents. It then describes the diverse virus-plant
      pathosystem scenarios possible at the interface between managed and natural
      vegetation and gives examples that illustrate situations where indigenous viruses
      emerge to damage introduced cultivated plants and newly introduced viruses become
      potential threats to biodiversity. These examples demonstrate how human
      activities increasingly facilitate damaging new encounters between plants and
      viruses worldwide. The likely effects of climate change on virus emergence are
      emphasised, and the major factors driving virus emergence, evolution and greater
      epidemic severity at the interface are analysed and explained. Finally, the kinds
      of challenges posed by rapidly changing world conditions to achieving effective
      control of epidemics of emerging plant viruses, and the approaches needed to
      address them, are described.

PMID- 19159653
TI  - Key determinants of resistance durability to plant viruses: insights from a model
      linking within- and between-host dynamics.
AB  - The emergence of new genotypes of parasites involves several evolutionary,
      epidemiological and ecological processes whose individual effects and
      interactions are difficult to disentangle using experimental approaches. Here, a
      model is proposed to investigate how these processes lead to the emergence of
      plant viral genotypes breaking down qualitative resistance genes. At the
      individual plant scale, selection, drift and mutation processes shape the
      evolution of viral populations from a set of differential equations. The spatial
      segregation of virus genotypes in their hosts is also considered. At the host
      population scale, the epidemiological dynamics is given by an individual-based
      algorithm. Global sensitivity analyses allowed ranking the ten demo-genetic and
      epidemiological parameters of the model according to their impact on the mean and
      variance of the risk of breakdown of a plant resistance. Demo-genetic parameters
      (number and nature of mutations involved in breakdown, fitness of mutant
      genotypes) had the largest impact on the mean breakdown risk, whereas
      epidemiological parameters had more influence on its standard deviation. It is
      discussed how these results can be used to choose the potentially most durable
      resistance genes among a pool of candidates. Finally, our analyses point out the
      parameters which should be estimated more precisely to improve durability
      predictions.

PMID- 19159654
TI  - Soil-borne viruses affecting cereals: known for long but still a threat.
AB  - A number of furo- and bymoviruses, which are naturally transmitted by the
      ubiquitous soil-borne protozoon Polymyxa graminis are of great economic
      importance for autumn-sown wheat, barley, rye, triticale, and oats. The two
      barley-affecting bymoviruses, Barley yellow mosaic virus and Barley mild mosaic
      virus, are widespread in Europe and East Asia. Production of wheat, rye, and
      triticale is threatened by three related furoviruses and two bymoviruses. Soil
      borne wheat mosaic virus mainly occurs in North America and Chinese wheat mosaic
      virus in Asia, whereas Soil-borne cereal mosaic virus predominates in Europe. The
      bymovirus Wheat yellow mosaic virus so far is restricted to Asia; Wheat spindle
      streak mosaic virus occurs in North America and Europe. Oat plants can be
      separately or mixed-infected by a bymo- and a furovirus, named Oat mosaic virus
      and Oat golden stripe virus, respectively. Because P. graminis cannot be
      controlled by chemicals and the viruses retain their infectivity in the resting
      spores for many years cultivation of resistant plants is the only means of
      preventing severe losses. The genetic variability of the known viruses and the
      sporadic reports of newly emerging pathogens, such as Aubian wheat mosaic virus,
      make continued resistance breeding and careful monitoring of field crops
      necessary.

PMID- 19159655
TI  - Differential changes of neuroactive amino acids in samples obtained from discrete
      rat brain regions after systemic administration of saxitoxin.
AB  - Aspartic acid, glutamic acid, gamma-amino-n-butyric acid (GABA) and 2
      aminoethanesulfonic acid are neuroactive amino acids. They are found in the
      central rat nervous system. Here, we have studied if a relationship exists
      between the presence of saxitoxin (STX) a paralytic poisoning shellfish (PSP) and
      the neuroactive amino acids. Samples of striatum (S), hypothalamus (H), mid brain
      (MB), frontal cortex (FC), brain stem (BS), right hemisphere (RH) and left
      hemisphere (LH) of rat brain were collected and analyzed for neuroactive amino
      acids (AAn(t)) by Aswad method (1984). Experiments, consisting of intraperitoneal
      injection of SXT (5 and 10microgkg(-1) body weight) to young male rats, evoked
      significant changes in AAn(t) above basal values. Aspartic and glutamic acid
      significantly increased for RH and LH (after 30min the increased was 116% and
      210%, P< or =0.001 over basal values, respectively). On the other hand, aspartic,
      glutamic, taurine and GABA significantly decreased for S (after 30min the
      decreased was 77.4%; 84%; 93.8% and 95.3%, P< or =0.001 over basal values,
      respectively). These results suggest that STX alters AAn(t). It is produced at
      least in part, because STX blocks voltage-gated sodium channels and this blockade
      could decrease AAn(t) release by exocytotic dependent mechanism of
      depolarization.

PMID- 19159656
TI  - Different immunomodulatory effects associated with sub-micrometer particles in
      ambient air from rural, urban and industrial areas.
AB  - Immunomodulatory effects of chemicals adsorbed to particles with aerodynamic
      diameter below 0.49 microm (PM(0.5)) collected in winter 2001 at three sampling
      points (industrial area [LPIn], traffic-influenced urban area [LPCi], and control
      area [LPCo]) of La Plata, Argentina, were investigated. The sampling of
      particulate matter was carried out with high-volume collectors using cascade
      impactors. PM(0.5)-adsorbed compounds were hexane-extracted by accelerated
      solvent extraction. For immunological investigations, human peripheral blood
      lymphocytes were activated by phytohemagglutinin and exposed to dimethyl
      sulfoxide dilutions of PM(0.5)-extracts for 24h. Vitality/proliferation was
      quantified using MTT, released interferon-gamma (IFN-gamma) and interleukin-4 (IL
      4) by ELISA. Cytokine production but not vitality/proliferation was significantly
      suppressed by all of the highest extract concentrations. Generally, suppression
      of IFN-gamma by PM(0.5)-extracts was stronger than those of IL-4. Based on
      administered mass of PM(0.5), all extracts suppressed IFN-gamma production nearly
      uniform. Contrary, LPCi-extracts exerted maximum IFN-gamma suppression based
      either on air volume or regarding PM(0.5)-adsorbed PAH. Also the ranking of
      PM(0.5)-associated effects on IL-4 production differs in dependence of the chosen
      reference points, either mass or [microg/ml] or air volume [m(3)/ml] related dust
      quantities in cell culture. Based on the corresponding air volume, LPCi-extracts
      inhibited IL-4 production to the maximum extend, whereas suppression of IL-4 was
      comparable based on concentrations. This indicates that not only the disparate
      PM(0.5)-masses in air cause varying impacts, but also that disparities in PM(0.5)
      adsorbed chemicals provoke different effects on immune responses and shifts in
      the regulatory balance that might have implications for allergy and cancer
      development.

PMID- 19159657
TI  - Differential time-course of the increase of antioxidant thiol-defenses in the
      acute phase after spinal cord injury in rats.
AB  - Spinal cord injury (SCI) is a world-wide health problem. After traumatic injury,
      spinal cord tissue starts a series of self-destructive mechanisms, known as the
      secondary lesion. The leading mechanisms of damage after SCI are excitotoxicity,
      free radicals' overproduction, inflammation and apoptosis. Metallothionein (MT)
      and reduced glutathione (GSH) are low-molecular-weight, cysteine-rich peptides
      able to scavenge free radicals. MT and GSH participation as neuroprotective
      molecules after SCI is unknown. The aim of the present study is to describe the
      changes of MT and GSH contents and GSH peroxidase (GPx) activity in the acute
      phase after SCI in rats. Female Wistar rats weighing 200-250g were submitted to
      spinal cord contusion model, by means of a computer-controlled device (NYU
      impactor). Rats receiving laminectomy were used as a control group. Animals were
      killed 2, 4, 12 and 24h after surgery. MT was quantified by the silver-saturation
      method, using atomic absorption spectrophotometry. GSH and GPx were assayed by
      spectrophotometry. Results indicate an increased MT content by effect of SCI,
      only at 4 and 24h, as compared to sham group values. Meanwhile, GSH was found
      decreased at 4, 12 and 24h after SCI. Interestingly, GPx activity was raised at
      all time points, indicating that this enzymatic defense is activated soon after
      SCI. Results suggest that thiol-based defenses, MT and GSH, are differentially
      expressed by spinal cord tissue to cope with the various processes of damage
      after lesion.

PMID- 19159658
TI  - Discovery and characterization of potent small molecule inhibitors of the high
      affinity proline transporter.
AB  - The mammalian proline transporter (PROT) is a high affinity Na(+)/Cl(-)-dependent
      transporter expressed in specific regions of the brain. It is homologous to other
      neurotransmitter transporters such as glycine, norepinephrine, serotonin, and
      dopamine transporters. PROT is enriched in glutamatergic synaptic terminals and
      may play an important role in the regulation of excitatory neurotransmission. No
      non-peptide small molecule inhibitors have been described for this transporter.
      To study its physiological role in the central nervous system and evaluate its
      potential as a therapeutic target, we established cell lines that stably express
      recombinant hPROT and characterized its kinetic properties for proline uptake. We
      then screened for inhibitors and identified a series of compounds that inhibit
      hPROT-mediated proline uptake. A known compound, benztropine, was found to
      inhibit hPROT with an IC(50) of 0.75microM. A series of novel compounds were also
      found, one of which, LP-403812, showed an IC(50) of approximately 0.1microM on
      both recombinant human and mouse PROT without significant inhibition of glycine
      and dopamine transporters at concentrations up to 10microM. This compound also
      inhibited proline transporter activity of mouse brain synaptosomes with the same
      potency. These inhibitors provide important tools for the understanding of PROT
      functions in the brain and may lead to the development of therapeutic agents for
      certain neurological disorders.

PMID- 19159659
TI  - Unusual circadian locomotor activity and pathophysiology in mutant CRY1
      transgenic mice.
AB  - In the widely accepted molecular model underlying mammalian circadian rhythm,
      cryptochrome proteins (CRYs) play indispensable roles as inhibitive components of
      the CLOCK-BMAL1-mediated transcriptional-translational negative feedback loop. In
      order to clarify yet uncovered aspects of mammalian CRYs in vivo, we generated
      transgenic (Tg) mice ubiquitously overexpressing CRY1 as well as CRY1 having a
      mutation in the dipeptide motif of cysteine and proline that is conserved beyond
      evolutional divergence among animal CRYs: cysteine414 of the motif was replaced
      with alanine (CRY1-AP). The mice overexpressing CRY1 (CRY1 Tg) exhibited robust
      circadian rhythms of locomotor activity. In sharp contrast, the mice
      overexpressing CRY1-AP (CRY1-AP Tg) displayed a unique circadian phenotype. Their
      locomotor free-running periods were very long (around 28h) with rhythm splitting:
      the bout of activity of CRY1-AP Tg mice was split into two equal components in
      constant darkness. Moreover, CRY1-AP Tg mice displayed abnormal entrainment
      behavior: their bout of activity shifted immediately in response to a shift of
      the light-dark cycles. In addition, we found that CRY1-AP Tg mice showed symptoms
      characteristic of diabetes mellitus. The results indicate that the motif of CRY1
      is crucial to the mammalian clock system and physiology.

PMID- 19159660
TI  - Interstitial cells of Cajal reduce in number in recto-sigmoid Hirschsprung's
      disease and total colonic aganglionosis.
AB  - Interstitial cells of Cajal (ICCs) play a key role in regulating gastrointestinal
      tract motility. The pathophysiological basis of colonic aperistalsis in
      Hirschsprung's disease (HD) is still not fully understood. Many studies reported
      that decreased numbers or disrupted networks of ICCs were associated with HD.
      Little information is available on the distribution of different subtypes of ICCs
      in HD. The aim of this study was to determine the alterations in density of
      different subtypes of ICC in colonic specimens of patients with total colonic and
      recto-sigmoid HD. Full thickness colonic specimens were obtained from five
      children with total colonic aganglionosis (TCA), sixteen with recto-sigmoid HD
      and seven controls. ICCs were visualized in frozen sections by c-Kit (CD117)
      fluorescent staining. In the control colon, c-Kit positive ICCs formed a dense
      network surrounding the myenteric plexus (IC-MY), along the submucosal surface of
      the circular muscle layer (IC-SM) and in the circular and longitudinal muscle
      layer (IC-IM). In the aganglionic region of the colon of the patients affected by
      HD, the number of ICCs (especially IC-IM and IC-SM) was markedly reduced and IC
      MY networks were disrupted. Nearly total lack of three subtypes of ICCs was
      observed in the TCA specimens. This study demonstrated the altered distribution
      of different subtypes of ICCs in the resected colon of patients with recto
      sigmoid HD and TCA. These findings suggest that the reduction of each subtype of
      ICCs may play an important role in the etiology of HD.

PMID- 19159661
TI  - Involvement of capsaicin-sensitive afferents and the Transient Receptor Potential
      Vanilloid 1 Receptor in xylene-induced nocifensive behaviour and inflammation in
      the mouse.
AB  - The inflammatory actions of xylene, an aromatic irritant and sensitizing agent,
      were described to be predominantly neurogenic in the rat, but the mechanism and
      the role of the Transient Receptor Potential Vanilloid 1 (TRPV1) capsaicin
      receptor localized on a subpopulation of sensory nerves has not been elucidated.
      This paper characterizes the involvement of capsaicin-sensitive afferents and the
      TRPV1 receptor in nociceptive and acute inflammatory effects of xylene in the
      mouse. Topical application of xylene on the paw induced a short, intensive
      nocifensive behaviour characterized by paw liftings and shakings, which was more
      intensive in Balb/c than in C57Bl/6 mice. Genetic deletion of the TRPV1 receptor
      as well as destroying capsaicin-sensitive nerve terminals with resiniferatoxin
      (RTX) pretreatment markedly reduced, but did not abolish nocifensive behaviours.
      In respect to the xylene-induced plasma protein extravasation detected by Evans
      blue leakage, significant difference was neither observed between the Balb/c and
      C57Bl/6 strains, nor the ear and the dorsal paw skin. These inflammatory
      responses were diminished in the RTX pretreated group, but not in the TRPV1 gene
      deleted one. Injection of the antioxidant N-acetylcysteine 15min prior to xylene
      smearing significantly reduced plasma protein extravasation at both sites. These
      results demonstrate that xylene-induced acute nocifensive behaviour is mediated
      by capsaicin-sensitive afferents via TRPV1 receptor activation in mice.
      Neurogenic inflammatory components play an important role in xylene-induced
      plasma protein extravasation, but independently of the TRPV1 ion channel.
      Reactive oxygen or carbonyl species participate in this process presumably via
      stimulation of the TRPA1 channel.

PMID- 19159662
TI  - Estrogen stimulates activity-regulated cytoskeleton associated protein (Arc)
      expression via the MAPK- and PI-3K-dependent pathways in SH-SY5Y cells.
AB  - Activity-regulated cytoskeleton associated protein (Arc) is known to be induced
      by synaptic plasticity following memory consolidation. Since estrogen has been
      shown to play an important role in synaptogenesis, a key aspect of the synaptic
      plasticity, we aimed to study the effects of estrogen on Arc expression in SH
      SY5Y human neuroblastoma cells. Using quantitative real-time PCR, Western blot,
      and confocal immunocytochemistry techniques we found that estrogen markedly
      increased Arc mRNA and protein expression in SH-SY5Y cells. Estrogen-activated
      Arc expression was mediated via mitogen-activated protein kinase (MAPK) and
      phosphoinositide-3 kinase (PI-3K), but not protein kinase C (PKC) and Rho
      associated kinase (ROCK), and in the estrogen receptor (ER)-dependent manner.
      Estrogen also significantly upregulated the dendritic spine scaffolding protein,
      postsynaptic density-95 (PSD-95), as well as expression of the presynaptic
      vesicle protein, synaptophysin. Our findings demonstrate the possible mechanisms
      of estrogen-induced synaptic plasticity, as well as memory consolidation.

PMID- 19159663
TI  - Glutathione S-transferase pi regulates UV-induced JNK signaling in SH-SY5Y
      neuroblastoma cells.
AB  - Activation of c-Jun N-terminal kinase (JNK) signaling pathway is a key event in
      apoptosis. The cellular mechanisms underlying the control of JNK catalytic
      activity before and immediately after stress in neuronal cells are still not
      completely understood. Under resting conditions the basal activity of JNK is low,
      since JNK is kept inactive by the presence of one or more endogenous repressors,
      including glutathione S-transferase pi (GSTpi). The aim of this study was to
      investigate the control of JNK signaling by GSTpi. We examined the modifications
      of GSTpi protein expression and oligomerization after UV irradiation-induced
      stress in human SH-SY5Y neuroblastoma cells. In parallel, we investigated the
      effect of UV irradiation on JNK activation and c-Jun phosphorylation, and whether
      apoptosis represents a functional consequence triggered by this signaling
      pathway. We show that in SH-SY5Y cells JNK phosphorylation and activation
      precedes c-Jun phosphorylation and caspase-3 cleavage. Importantly, the increase
      of JNK enzymatic activity correlates with the dissociation of GSTpi-JNK complexes
      and the increased concentration of GSTpi multimer forms. Results presented herein
      show for the first time direct interaction between JNK and GSTpi in SH-SY5Y
      neuroblastoma cells, and suggest that in these cells GSTpi may serve as a
      regulator of JNK catalytic activity. This work contributes to further elucidate
      the mechanisms underlying the regulation of JNK activity under stress conditions.

PMID- 19159664
TI  - Cell-dependent physiological synaptic action of morphine in the rat habenular
      nucleus: morphine both inhibits and facilitates excitatory synaptic transmission.
AB  - Although several lines of evidence have suggested that the activity of thalamic
      neurons is modulated by opioids, the mechanism by which morphine in the thalamus
      regulates the release of excitatory neurotransmitters remains unclear. In the
      present study, we investigated the synaptic modulation of morphine to regulate
      excitatory synaptic transmission, probably glutamatergic transmission, in
      habenular nucleus (Hb) and centrolateral nucleus (CL) neurons in the rat
      thalamus. Using the whole-cell patch-clamp technique, we found dual modulation by
      morphine in Hb neurons: morphine caused either inhibition or facilitation of the
      miniature excitatory postsynaptic current (mEPSC) frequency in the Hb. In Hb
      neurons that showed a morphine-induced decrease in the mEPSC frequency, the mEPSC
      amplitude was also decreased in the presence of morphine. In contrast, the mEPSC
      amplitude was markedly increased in Hb neurons that showed a morphine-induced
      increase in the mEPSC frequency. We also observed a significant decrease in the
      mEPSC frequency with morphine in CL neurons without any change in the mEPSC
      amplitude, whereas morphine did not facilitate the mEPSC frequency in CL neurons.
      These results suggest that morphine may induce cell-dependent dual modulation of
      glutamatergic synaptic transmission in the Hb.

PMID- 19159665
TI  - Effects of transient focal cerebral ischemia in mice deficient in puma.
AB  - Bcl-2 homology domain 3 (BH3)-only pro-apoptotic proteins may play an important
      role in upstream cell death signaling pathways underlying ischemic brain injury.
      Puma is a potent BH3-only protein that can be induced via p53, FoxO3a and
      endoplasmic reticulum stress pathways and is upregulated by global cerebral
      ischemia. To more completely define the contribution of Puma to ischemic brain
      injury we measured the expressional response of Puma to transient focal cerebral
      ischemia in mice and also compared infarct volumes in puma-deficient versus puma
      expressing mice. Real-time quantitative PCR determined puma mRNA levels were
      significantly increased 8h after 90min middle cerebral artery (MCA) occlusion in
      the ipsilateral cortex, while expression remained unchanged contralaterally. Puma
      protein levels were also increased in the ischemic cortex over the same period.
      However, cortical and striatal infarct volumes were not significantly different
      between puma-deficient and puma-expressing mice at 24h, and no differences
      between genotypes were found for post-ischemic neurological deficit scores. These
      data demonstrate that focal cerebral ischemia is associated with puma induction
      but suggest that Puma does not contribute significantly to lesion development in
      the present model.

PMID- 19159666
TI  - Codon-pair usage and genome evolution.
AB  - The aim of this paper is to demonstrate possible evolutionary constraints that
      shape codon-pair context. The distributions of numbers of modes (DNM) of codon
      pairs in protein coding sequences (CDSs) and the frequency of base triplet pairs
      in intergenic sequences (IGSs) are analyzed in 110 fully sequenced genomes. We
      propose that these distributions are in accordance with a gamma distribution. By
      studying the shape parameter alpha value of gamma distribution a distinct
      relation between the alpha value and the genome evolution is obtained. For codon
      pairs in CDSs, the alpha value increases in the order Archaea, Bacteria, and
      Eukaryota, and divides the species into three evolutionary groups, Archaea,
      Bacteria and Eukaryota. For triplet pairs in IGSs, on the other hand, the alpha
      value classifies the species into two groups, one is Bacteria and the other is
      Archaea and Eukaryota. The findings suggest that the codon-pair context could be
      an important determinant for phylogeny of individual species, and indicate the
      existence of fundamental differences of evolutional constraints imposed on CDSs
      and IGSs among Archaea, Bacteria, and Eukaryota.

PMID- 19159667
TI  - Reliable fusion PCR mediated by GC-rich overlap sequences.
AB  - Recombinant DNA technology largely depends upon Escherichia coli plasmid
      construction via restriction enzyme digestion and DNA ligation. Overlap extension
      PCR is another simple technique for constructing recombinant DNA but is not
      commonly used. This is likely due to the inefficiency of fusion after the
      annealing of overlaps that are generally designed from authentic sequences in the
      DNA fragments. In our current study, we describe the development of novel overlap
      sequences that can be used for the construction of fusion DNA fragments,
      including the one-step fusion of three fragments in a single PCR and also for in
      frame fusions. Novel poly G or C stretches showed strong and also specific
      annealing to the complementary sequences in the fusion PCR. This DNA fusion
      method is thus both a simple and versatile recombinant DNA technique.

PMID- 19159668
TI  - Enhancement of oral moisture using tablets containing extract of Capparis
      masaikai Levl.
AB  - AIM OF THE STUDY: This study was performed to examine the effects of tablets
      containing an extract of Capparis masaikai Levl. (M-tablets) on enhancing oral
      moisture. SUBJECTS AND METHODS: The moistening effect of M-tablets was examined
      in 21 healthy subjects aged 25.1+/-2.4 (mean+/-S.D.) years in comparison with
      control tablets. After sucking tablets, the oral moisture was measured using a
      saliva wetness tester and a moisture checker. To evaluate the effects of the M
      tablets on oral conditions, additional 50 subjects aged 30.6+/-7.5 years were
      examined. The subjects recorded changes in refreshment, oral moisture, ease in
      speaking, and taste of water using a visual analog scale (VAS). RESULTS: The L
      SALIVO value of the M-tablet increased significantly from 1.83+/-0.17 (mean+/
      S.E.M.) at baseline to 3.02+/-0.21 at 15 min (P<0.01). The Mucus((R)) value of
      the M-tablet also increased from 37.50+/-0.22 at baseline to 38.30+/-0.26 at 15
      min (P<0.01). The VAS value for oral moisture increased significantly from 47.4+/
      2.0 to 69.6+/-2.2 after taking the M-tablet (P<0.01). The VAS value for taste of
      water also increased from 50.0+/-1.1 to 66.7+/-3.2 (P<0.01). CONCLUSION: These
      results suggest that M-tablets are useful for enhancing oral moisture, which
      leads to improvement of oral conditions.

PMID- 19159669
TI  - Reproducible chemical-induced changes in gene expression profiles in human
      hepatoma HepaRG cells under various experimental conditions.
AB  - The use of in vitro human liver cell models is an attractive approach in
      toxicogenomic studies designed to analyze gene expression changes induced by a
      toxic chemical. However, in such studies, reliability, reproducibility and
      interlaboratory concordance of microarrays, as well as the choice of the most
      suitable cell model, remain a matter of debate. This work was aimed at evaluating
      the robustness of microarray technologies and the suitability of the highly
      differentiated human HepaRG cell line in the investigation of gene expression
      changes induced by a toxic compound in human liver. The influence of various
      experimental conditions including cell cultures grown at different test sites,
      different generations of microarrays, RNA analysis platforms and softwares, was
      tested on gene expression profiles induced by a 20h treatment with an 8mM
      concentration of phenobarbital as the toxic compound. As many as 1099 genes (p
      value<0.01 and 1.5-fold-change), representing 74% and 30% of the signature genes
      detected with Agilent 22 and 44K pangenomic microarrays, respectively, were shown
      to be modulated in common in six independently performed experiments. The most
      modulated genes included both those known to be regulated by phenobarbital, such
      as cytochromes P450 and membrane transporters, and those involved in oxidative
      stress, inflammation and apoptosis, typifying a toxic insult. These data provide
      strong support for the use of a toxicogenomic approach for the in vitro
      prediction of chemical toxicity, and for the choice of human HepaRG cells as a
      promising model system for human hepatotoxicity testing.

PMID- 19159670
TI  - Prunella vulgaris extract and rosmarinic acid suppress lipopolysaccharide-induced
      alteration in human gingival fibroblasts.
AB  - Periodontitis is a chronic disease associated with inflammation of the tooth
      supporting tissues. The inflammation is initiated by a group of gram-negative
      anaerobic bacteria. These express a number of irritating factors including a
      lipopolysaccharide (LPS), which plays a key role in periodontal disease
      development. Plant extracts with anti-inflammatory and anti-microbial properties
      have been shown to inhibit bacterial plaque formation and thus prevent chronic
      gingivitis. In this study we tested effects of Prunella vulgaris L. extract (PVE;
      5, 10, 25microg/ml) and its component rosmarinic acid (RA; 1microg/ml) on LPS
      induced oxidative damage and inflammation in human gingival fibroblasts. PVE and
      RA reduced reactive oxygen species (ROS) production, intracellular glutathione
      (GSH) depletion as well as lipid peroxidation in LPS-treated cells. Treatment
      with PVE and RA also inhibited LPS-induced up-regulation of interleukin 1beta (IL
      1beta), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and
      suppressed expression of inducible nitric oxide synthase (iNOS). The results
      indicate that PVE and RA are able to suppress LPS-induced biological changes in
      gingival fibroblasts. The effects of PVE and RA are presumably linked to their
      anti-inflammatory activities and thus use of PVE and RA may be relevant in
      modulating the inflammation process, including periodontal disease.

PMID- 19159671
TI  - Inter-laboratory comparison of human renal proximal tubule (HK-2) transcriptome
      alterations due to Cyclosporine A exposure and medium exhaustion.
AB  - There is an acknowledged need to promote and further develop in vitro techniques
      in order to achieve the goal of improved risk assessment of chemicals and
      pharmaceuticals to humans. The EU 6th framework project "PREDICTOMICS" was
      established in order to contribute to the further development of in vitro
      toxicology, with a particular focus on emerging techniques including
      toxicogenomics. DNA microarray technology is being used more frequently in the in
      vitro field, however, only very few studies have assessed the reproducibility of
      this technique with respect to in vitro toxicology. To this end we conducted an
      interlaboratory comparison to test the reproducibility of transcriptomic changes
      induced by the immunosuppressive agent, Cyclosporine A (CsA) on the human renal
      proximal tubular cell line, HK-2 cell. Four European laboratories took part in
      this study. Under standardised conditions, each laboratory treated HK-2 cells
      with 5microM CsA for 12 and 48h. RNA was isolated and hybridised to Affymetrix
      HGU-133 plus two arrays at three different sites. Analysis of the transcription
      profiles demonstrated that one laboratory clustered away from the other
      laboratories, potentially due to an inclusion of a trypsinisation step by this
      laboratory. Once the genes responsible for this separate clustering were removed
      all laboratories showed similar expression profiles. There was a major impact of
      time since feed, due to medium exhaustion in the 48h arrays compared to the 12h
      arrays, regardless of CsA treatment. Biological processes including general
      vesicle transport, amino acid metabolism, amino acid transport and amino acid
      biosynthesis were over-represented due to time since feed, while cell cycle, DNA
      replication, mitosis and DNA metabolism were under-represented. CsA responsive
      genes were involved in cell cycle, the p53 pathway and Wnt signaling.
      Additionally there was an overlap of differentially expressed genes due to CsA
      and medium exhaustion which is most likely due to CsA induced glycolysis. The
      glucose deprivation dependent genes HspA5 and GP96 and the Hsp70 chaperones
      DNAJ/Hsp40, DNAJ/HspB9, DNAJ/HspC3 DNAJ/HspC10 were induced by both CsA and
      medium exhaustion. We conclude that under standardised conditions the application
      of Affymetrix DNA microarrays to in vitro toxiciological studies are
      satisfactorily reproducible. However, confounding factors such as medium
      exhaustion must also be considered in such analyses.

PMID- 19159672
TI  - Acutoxbase, an innovative database for in vitro acute toxicity studies.
AB  - Acutoxbase is as an internet-based database developed for coherent management of
      all information relevant to the EU integrated project 'A-Cute-Tox'
      (www.acutetox.org), which aims to optimise and prevalidate an in vitro testing
      strategy for predicting acute human toxicity. The database consists of two
      principal parts for archiving in vitro and in vivo data, respectively. The in
      vitro part, designed following the principles of Good Cell Culture Practice
      (GCCP), provides a standard format for collection of in vitro data, together with
      detailed descriptions of methodologies (Standard Operating Procedures, SOPs),
      generated by research laboratories participating in the project. In the course of
      the study 97 reference chemicals were tested in approximately 100 in vitro
      assays, including models for general acute cytotoxicity, metabolism-mediated
      toxicity, biokinetics, haemato-, immuno-, neuro-, nephro-, and hepatotoxicity.
      The in vivo part compiles mammalian acute toxicity studies derived from published
      literature and human acute poisoning cases available from clinical reports. The
      database has proven to be a useful tool for a quality controlled transfer and
      organisation of large in vitro and in vivo toxicological data sets. At present
      time, Acutoxbase is under continuous development, and it will be available for
      the broad circles of toxicologists and physicians in a near future.

PMID- 19159673
TI  - Psychological stress increases expression of IL-10 and its homolog IL-19 via beta
      adrenoceptor activation: reversal by the anxiolytic chlordiazepoxide.
AB  - Recent studies from our laboratory indicate that psychological stress is a potent
      inducer of the anti-inflammatory cytokine interleukin (IL)-10, raising the
      possibility that the IL-10 family of cytokines may be key mediators of stress
      induced immunosuppression. In this study we examined the impact of psychological
      stress (restraint stress) on expression of IL-10, and the novel IL-10 family
      members IL-19, IL-20 and IL-24 in mouse spleen following an in vivo challenge
      with lipopolysaccharide (LPS). We found that stressor exposure significantly
      augmented LPS-induced IL-10 expression. Similarly, IL-19 expression was induced
      by LPS, and this was significantly enhanced by restraint stress. In contrast,
      expression of IL-24 was not significantly altered by LPS or stress, and
      expression of IL-20 was largely not detectable in vivo in either saline or LPS
      treated animals. Consistent with a role for sympathetic nervous system (SNS)
      activation in stress-induced immune regulation, the sympathetic neurotransmitter
      noradrenaline increased LPS-induced IL-10 and IL-19 expression in splenocytes and
      dendritic cells, and the ability of noradrenaline to induce expression of these
      cytokines was blocked by pre-treatment with the beta-adrenoceptor antagonist
      propranolol. Similarly, pre-treatment of mice with the peripherally acting beta
      adrenoceptor antagonist nadolol completely blocked the stress-induced increase in
      IL-10 and IL-19 mRNA expression. Finally, pre-treatment with the benzodiazepine
      anxiolytic chlordiazepoxide prevented the stress-induced increase in IL-10 and IL
      19 expression. Taken together, these data demonstrate that psychological stress
      induces expression of the IL-10 and its homolog IL-19 via activation of beta
      adrenoceptors, and the ability of stress to induce these cytokines is prevented
      by treatment with the anxiolytic chlordiazepoxide. The findings suggest that
      stress enhances the production of immunosuppressive cytokines, which may impact
      on stress-related disease processes.

PMID- 19159675
TI  - The effects of lead exposure on placental NF-kappaB expression and the
      consequences for gestation.
AB  - The present study was designed to investigate the toxicity of lead exposure on
      the placenta at different dosages and the relationship with placental expression
      of NF-kappaB. A total of 67 unrelated Han Chinese pregnant women and 108 Wistar
      rats were included in this study. The rats were randomly divided into four groups
      for consumption of water with or without 0.025% lead acetate during various
      gestational periods; blood samples and placenta were harvested for analysis.
      Blood lead content was determined by atomic absorption spectrophotometry.
      Placental NF-kappaB expression was evaluated by immunohistochemistry. Placental
      cytoarchitecture was examined by histopathology and electronic microscopy. Fetal
      body weight, body length and placental weight was significantly lower (p<0.05) in
      the lead-exposed rats compared to controls. Maternal blood lead levels in the
      rats negatively correlated with placental weight (r=0.652, p<0.01). Rat placenta
      showed focal necrosis in the decidua with trophoblast degeneration and fibrin
      deposition. Mitochondria were swollen and decreased in number, rough endoplasmic
      reticula were distended and ribosomal number on membranes decreased. In the human
      placenta, we did not find abnormal cytoarchitecture. On the other hand, placental
      expression of NF-kappaB in lead-exposed rats was significantly higher than that
      in controls and the expression of NF-kappaB in human placenta was positively
      correlated with maternal blood lead levels (r=0.663, p<0.01). These findings
      suggest that lead exposure at various gestational periods produce varied effects,
      with NF-kappaB activation following lead exposure. Injury to cytoplasmic
      organelles may interfere with the nutrition and oxygen exchange between mother
      and fetus, which may be contribute to abnormal pregnancy outcomes.

PMID- 19159676
TI  - Effects of environmental tobacco smoke in vivo on rhesus monkey semen quality,
      sperm function, and sperm metabolism.
AB  - The objective of this study was to use a non-human primate model to examine the
      effect of environmental tobacco smoke (ETS) in vivo on semen quality, sperm
      function, and sperm metabolism. Four adult rhesus macaques (Macaca mulatta) were
      exposed to ETS for six months, and semen samples were collected every week for
      evaluation. ETS exposure in vivo did not affect semen quality and sperm function.
      The sperm X:Y chromosome ratio remained unchanged after ETS exposure. The sex
      ratio of the embryos fertilized by ETS-exposed males was not different from the
      control male. However, sperm showed changes in metabolome detected by NMR during
      the ETS exposure. We concluded that with the duration and level of ETS exposure
      in this study, semen quality and sperm function were not affected, whereas sperm
      did undergo metabolic changes with ETS exposure in vivo.

PMID- 19159674
TI  - Overlapping but distinct effects of genistein and ethinyl estradiol (EE(2)) in
      female Sprague-Dawley rats in multigenerational reproductive and chronic toxicity
      studies.
AB  - Genistein and ethinyl estradiol (EE(2)) were examined in multigenerational
      reproductive and chronic toxicity studies that had different treatment intervals
      among generations. Sprague-Dawley rats received genistein (0, 5, 100, or 500 ppm)
      or EE(2) (0, 2, 10, or 50 ppb) in a low phytoestrogen diet. Nonneoplastic effects
      in females are summarized here. Genistein at 500 ppm and EE(2) at 50 ppb produced
      similar effects in continuously exposed rats, including decreased body weights,
      accelerated vaginal opening, and altered estrous cycles in young animals. At the
      high dose, anogenital distance was subtly affected by both compounds, and a
      reduction in litter size was evident in genistein-treated animals. Genistein at
      500 ppm induced an early onset of aberrant cycles relative to controls in the
      chronic studies. EE(2) significantly increased the incidence of uterine lesions
      (atypical focal hyperplasia and squamous metaplasia). These compound-specific
      effects appeared to be enhanced in the offspring of prior exposed generations.

PMID- 19159677
TI  - The cellular composition and morphological organization of the rostral migratory
      stream in the adult human brain.
AB  - The rostral migratory stream (RMS) is the major pathway by which progenitor cells
      migrate from the subventricular zone (SVZ) to the olfactory bulb (OB) in rodents,
      rabbits and primates. However, the existence of an RMS within the adult human
      brain has been elusive. Immunohistochemical studies utilising cell-type specific
      markers for early progenitor cells (CD133), proliferating cells (PCNA),
      astrocytes and type B cells (GFAP) and migrating neuroblasts (PSA-NCAM), reveal
      that the adult human RMS is organized into layers containing glial cells,
      proliferating cells and neuroblasts. In addition, the RMS is arranged around a
      remnant of the ventricular cavity that extends from the SVZ to the OB as seen by
      immunohistological staining analysis and electron microscopy, showing the
      presence of basal bodies and a typical 9+2 arrangement of tubulin in tufts of
      cilia from all levels of the RMS. Overall, these findings suggest that a pathway
      of migratory progenitor cells similar to that seen in other mammals is present
      within the adult human brain and that this pathway could provide for neurogenesis
      in the human forebrain. These findings contribute to the scientific understanding
      of adult neurogenesis and establish the detailed cytoarchitecture of this novel
      neurogenic niche in the human brain.

PMID- 19159678
TI  - Elevation of oxidative-damage biomarkers during aging in F2 hybrid mice:
      protection by chronic oral intake of resveratrol.
AB  - Resveratrol (RSV), a naturally occurring phytoalexin that can be found in red
      wine, berries, and peanuts, has been shown to extend both mean and maximum life
      span in model organisms. RSV has also been reported to shift the physiology of
      middle-aged mice on a high-calorie diet toward that of mice on a standard diet.
      These beneficial effects of RSV have been suggested to resemble caloric
      restriction. Our study in F2 four-way cross-hybrid mice was the first to evaluate
      the effects of aging and long-term RSV treatment (14.09+/-3.4 mg/L in drinking
      water for 6 or 12 months) on biomarkers of oxidative damage to DNA, 8-hydroxy-2'
      deoxyguanosine (8OHdG); lipid, 8-iso-prostaglandin(2 alpha) (8-iso-PGF(2 alpha));
      and protein, protein carbonyl content (PCC). There was a significant age
      dependent accumulation of oxidative damage to DNA, lipid, and protein as well as
      a clear increase in urine 8-iso-PGF(2 alpha) levels in the majority of mouse
      tissues. Rates of age-dependent increases in damage biomarkers varied between
      tissues. Chronic RSV treatment elevated total RSV plasma levels and reduced the
      observed age-dependent accumulation of (1) 8OHdG in liver and heart, (2) 8-iso
      PGF(2 alpha) in heart and urine, and (3) PCC in liver and kidney. However, a 12
      month RSV intake resulted in significant elevation of 8-iso-PGF(2 alpha) and PCC
      in kidney. Our studies demonstrate that RSV treatment consistently attenuated
      oxidative damage in tissues where age-related oxidative damage accumulation was
      prominent, but also suggested that chronic RSV treatment may induce
      nephrotoxicity.

PMID- 19159681
TI  - Hsp90 and a tyrosine embedded in the Hsp90 recognition loop are required for the
      Fer tyrosine kinase activity.
AB  - Hsp90 is a key regulator of tyrosine kinases activity and is therefore considered
      as a promising target for intervention with deregulated signaling pathways in
      malignant cells. Here we describe a novel Hsp90 client - the intracellular
      tyrosine kinase, Fer, which is subjected to a unique regulatory regime by this
      chaperone. Inhibition of Hsp90 activity led to proteasomal degradation of the Fer
      enzyme. However, circumventing the dependence of Fer accumulation on Hsp90,
      revealed the dependence of the Fer kinase activity and its ability to
      phosphorylate Stat3 on the chaperone, expressing the necessity of Hsp90 for its
      function. Mutation analysis unveiled a tyrosine (Tyr(616)) embedded in the Hsp90
      recognition loop, which is required for the kinase activity of Fer. Replacement
      of this tyrosine by phenylalanine (Y616F) disabled the auto-phosphorylation
      activity of Fer and abolished its ability to phosphorylate Stat3. Notably,
      surrounding the replaced Y616F with subtle mutations restored the auto and trans
      phosphorylation activities of Fer suggesting that Y(616) is not itself an
      essential auto-phosphorylation site of the kinase. Taken together, our results
      portray Hsp90 and its recognition loop as novel positive regulators of the Fer
      tyrosine kinase stability and activity.

PMID- 19159679
TI  - Immuno-spin trapping of protein and DNA radicals: "tagging" free radicals to
      locate and understand the redox process.
AB  - Biomolecule-centered radicals are intermediate species produced during both
      reversible (redox modulation) and irreversible (oxidative stress) oxidative
      modification of biomolecules. These oxidative processes must be studied in situ
      and in real time to understand the molecular mechanism of cell adaptation or
      death in response to changes in the extracellular environment. In this regard, we
      have developed and validated immuno-spin trapping to tag the redox process,
      tracing the oxidatively generated modification of biomolecules, in situ and in
      real time, by detecting protein- and DNA-centered radicals. The purpose of this
      methods article is to introduce and update the basic methods and applications of
      immuno-spin trapping for the study of redox biochemistry in oxidative stress and
      redox regulation. We describe in detail the production, detection, and location
      of protein and DNA radicals in biochemical systems, cells, and tissues, and in
      the whole animal as well, by using immuno-spin trapping with the nitrone spin
      trap 5,5-dimethyl-1-pyrroline N-oxide.

PMID- 19159682
TI  - Expression of tyrosine hydroxylase in the striatum of atipamezole-treated rats.
AB  - The effect of atipamezole, an alpha-2-adrenergic antagonist, was examined on the
      expression of tyrosine hydroxylase, the rate-limiting enzyme of synthesis of
      catecholamines such as dopamine, in the rat striatum. It has been reported that
      the alpha-2-adrenergic pathways can modulate the levodopa- and apomorphine
      induced dopaminergic turning behavior in the rat model of Parkinson's disease. It
      is also known that catecholamines have a feed back inhibition of TH activity.
      Since atipamezole can increase the levodopa-induced turning behavior, a potential
      feed back effect on the TH enzyme was estimated by measuring the TH protein. In
      the present study, the atipamezole and/or levodopa treatments did not clearly
      affect on the amount of TH in the rat striata when measured by Western blot.
      However, it is possible that the sensitivity of the method limits the detection
      of changes, and therefore further studies are needed to examine the potential of
      atipamezole and/or levodopa effects on the regulation of TH enzyme, e.g., by
      measuring the phosphorylation status, activity and mRNA expression of TH enzyme.

PMID- 19159680
TI  - Deregulation of Tpl2 and NF-kappaB signaling and induction of macrophage
      apoptosis by the anti-depressant drug lithium.
AB  - Lithium is an anti-depressant drug that also possesses immunomodulatory
      functions. The anti-inflammatory effect of lithium is thought to involve
      activation of the transcription factor CREB, although the underlying mechanism is
      incompletely understood. We show here that in macrophages lithium stimulates
      Tpl2, a MAP kinase kinase kinase (MAP3K) known to mediate activation of
      extracellular signal regulated kinase (ERK) and the downstream target CREB.
      Lithium activates Tpl2 by inducing degradation of p105, an NF-kappaB precursor
      protein that functions as a physiological inhibitor of Tpl2. This novel function
      of lithium does not involve inhibition of a well-characterized lithium target,
      GSK3beta, since other known GSK3beta inhibitors do not induce p105 degradation or
      Tpl2 activation. Lithium also promotes the activation of Tpl2 and ERK by the TLR4
      ligand LPS. On the other hand, prolonged incubation of macrophages with lithium
      results in dramatic loss of p105 and inhibition of LPS-stimulated NF-kappaB
      activation. Consequently, lithium both attenuates LPS-mediated pro-inflammatory
      gene induction and induces apoptosis in macrophages. These results provide novel
      insight into the anti-inflammatory function of lithium.

PMID- 19159683
TI  - Nonlinear turnover models for systems with physiological limits.
AB  - Physiological limits have so far not played a central role in mechanism-based
      pharmacodynamic modeling, except in models of feedback, where physiological
      limits act intrinsically on deviations from a pre-set physiological ground state
      (e.g., the baseline value or a set-point value). However, recently these concepts
      were introduced in turnover models acting on the production or loss of response,
      respectively, even for simple (nontolerant) systems. In the latter case, the
      physiological limit kicks in when the state variable (response) approaches either
      a lower or an upper limit, not before. In this paper we propose a new approach
      with either one (lower or upper) limit or two (simultaneously acting lower and
      upper) limits (dual limits). We present an analytical mathematical treatment as
      well as a numerical treatment via model simulations. This approach allows for a
      baseline value to be only weakly dependent on the lower/upper physiological
      limit. It also allows dual limits, one below and one above, which is attractive
      because it may be applicable to commonly studied physiological and biochemical
      systems such as turnover of water or fat.

PMID- 19159684
TI  - Evaluation of the nonparametric estimation method in NONMEM VI.
AB  - PURPOSE: In NONMEM VI, a novel method exists for estimation of a nonparametric
      parameter distribution. The parameter distributions are approximated by discrete
      probability density functions at a number of parameter values (support points).
      The support points are obtained from the empirical Bayes estimates from a
      preceding parametric estimation step, run with the First Order (FO) or First
      Order Conditional Estimation (FOCE) methods. The purpose of this work is to
      evaluate this new method with respect to parameter distribution estimation.
      METHODS: The performance of the method, with special emphasis on the analysis of
      data with non-normal distribution of random effects, was studied using Monte
      Carlo (MC) simulations. RESULTS: The mean value (and ranges) of absolute relative
      biases (ARBs, %) in parameter distribution estimates with nonparametric methods
      preceded with FO and FOCE were 0.80 (0.1-3.7) and 0.70 (0-3), respectively, while
      for parametric methods, these values were 23.74 (3.3-97.5) and 4.38 (0.1-17.9),
      for FO and FOCE, respectively. The nonparametric estimation method in NONMEM
      could identify non-normal parameter distributions and correct bias in parameter
      estimates seen when applying the FO estimation method. CONCLUSIONS: The method
      shows promising properties when analyzing different types of pharmacokinetic (PK)
      data with both the FO and FOCE methods as preceding steps.

PMID- 19159685
TI  - The GGN and CAG repeat polymorphisms in the exon-1 of the androgen receptor gene
      are, respectively, associated with insulin resistance in men and with
      dyslipidemia in women.
AB  - The human androgen receptor (AR) gene possesses two trinucleotide repeats of CAG
      and GGN in exon-1. The GGN repeat affects the amount of AR protein translated,
      while the CAG repeat affects the efficiency of AR transcriptionaly. In this
      study, we have genotyped these polymorphic tracts in a representative sample of
      557 Caucasian adult individuals (314 women and 243 men) from the Canary Islands,
      Spain (the ENCA Study), and investigated their association with fasting serum
      levels of lipids, glucose and insulin. The number of CAG repeats in women
      (expressed as the average length of the two alleles) was inversely correlated
      with serum levels of LDL-cholesterol (Spearman rho=-0.179; P<0.01). Women with an
      average number of CAG repeats in the upper tertile showed significantly lower
      levels of LDL-cholesterol than those grouped in the lower and middle tertile,
      after adjusting for age, body mass index, waist-to-hip ratio, smoking and alcohol
      drinking. The number of GGN repeats in men was correlated with fasting insulin
      levels (Spearman rho=-0.206; P<0.01), the homeostasis model assessment of insulin
      resistance (HOMA-IR; Spearman rho=-0.230; P<0.01) and the McAuley index of
      insulin sensitivity (Spearman rho=0.194; P<0.01). Men with a number of GGN
      repeats in the upper tertile showed lower levels of insulin and HOMA and a higher
      level of the McAuley index than those grouped in the lower and middle tertile,
      after adjusting for the variables listed above. These results support the
      hypothesis that the longer alleles of the CAG and GGN polymorphisms in the exon-1
      of the AR gene, indicative of lower androgenic signaling, respectively protect
      women from developing dyslipemia and men from developing insulin resistance.

PMID- 19159686
TI  - Androgen-induced human breast cancer cell proliferation is mediated by discrete
      mechanisms in estrogen receptor-alpha-positive and -negative breast cancer cells.
AB  - Androgens have important physiological effects in women. Not only are they the
      precursor hormones for estrogen biosynthesis in the ovaries and extragonadal
      tissues, but also act directly via androgen receptors (ARs) throughout the body.
      Studies of the role of androgens on breast cancer development are controversial
      and the mechanisms involved are not fully understood. In this report we
      demonstrate that a non-aromatizable androgen metabolite, dihydrotestosterone
      (DHT), stimulated cell proliferation in vitro of both estrogen receptor-alpha (ER
      alpha)-positive MCF-7 cells and ER-alpha-negative MDA-MB-231 human breast cancer
      cells. A contribution of ER to the proliferative effect of DHT in MCF-7 cells was
      supported by actions of small interfering RNA (siRNA) ER-alpha transfection and
      of the specific inhibitor of ER, ICI 182,780 to block DHT-induced proliferation.
      A contribution of the possible conversion of DHT to androstane-3alpha, 17beta
      diol was not excluded in these MCF-7 cell studies. In MDA-MB-231 cells, a novel
      mechanism was implicated, in that anti-integrin alphavbeta3 or an Arg-Gly-Asp
      (RGD) peptide targeted at a small molecule binding domain of the integrin
      eliminated the DHT effect on cell proliferation. Anti-integrin alphavbeta3 did
      not affect DHT action on MCF-7 cells. A contribution from classical androgen
      receptor to the DHT effect in each cell line was excluded. A proliferative DHT
      signal is transduced in both ER-alpha-positive and ER-alpha-negative breast
      cancer cells, but by discrete mechanisms.

PMID- 19159687
TI  - Expression level of enzymes related to in situ estrogen synthesis and
      clinicopathological parameters in breast cancer patients.
AB  - In order to evaluate the importance of estrogen production in tumor and
      surrounding tissues, we measured mRNA expression levels of 5 enzymes
      participating to estrogen synthesis in situ and 4 breast cancer-related proteins
      in 27 pairs of tumor and non-malignant tissues. Steroid sulfatase (STS) mRNA was
      more frequently detected in tumor tissues rather than in their non-malignant
      counterparts. Estrogen sulfotransferase (EST) was constantly expressed with high
      level not only in tumor tissues but also in their surrounding non-malignant
      counterparts. In contrast, mRNA expression levels of aromatase, and 17beta
      hydroxysteroid dehydrogenase type I and II were relatively low and detected only
      in small proportion of the patients. We also measured the mRNA expression levels
      of the same nine genes in tumor tissues of 197 breast cancer patients, and
      analyzed relationship between the mRNA expression level and the
      clinicopathological parameters. The mRNA expression levels of STS, aromatase and
      erbB2 in tumor tissues increased as breast cancer progressed. The tumoral mRNA
      expression levels of STS, estrogen receptor beta, and erbB2 in patients with
      recurrence were higher than those in patients without recurrence. Upregulation of
      STS expression plays an important role in tumor progression of human breast
      cancer and is considered to be responsible for estrogen production in tumor and
      surrounding tissues.

PMID- 19159688
TI  - Testosterone action on erythropoiesis does not require its aromatization to
      estrogen: Insights from the testosterone and estrogen treatment of two aromatase
      deficient men.
AB  - Androgens act on erythropoiesis, but the relative role of testosterone (T) and
      estradiol (E(2)) on erythropoietic parameters in men is a poorly investigated
      issue. In order to evaluate separately the effects on erythropoiesis of high-dose
      T administration alone and of physiological dose of E(2) administration alone two
      adult men with aromatase deficiency were assessed before and during each
      treatment. Blood cell count, hemoglobin (Hb), hematocrit (Hct), erythrocyte mean
      cell volume (MCV), erythrocyte mean corpuscular hemoglobin (MCH), erythrocyte
      mean corpuscular hemoglobin concentration (MCHC), serum ferritin, iron and total
      iron-binding capacity (TIBC), serum erythropoietin, serum total testosterone and
      estradiol were evaluated. Hb, Hct and red cell count rose during testosterone
      treatment, consistently with the increase in circulating testosterone, but failed
      to increase during estradiol treatment. A decrease in Hb, Hct and red cell count
      was recorded in one of the two subjects during estradiol treatment, with a
      concomitant decrease in serum testosterone. Circulating T alone is capable of and
      sufficient to influence erythropoiesis, especially at supraphysiological dosage,
      while circulating E(2) have not the same effect on erythropoietic parameters,
      suggesting the hypothesis that the erythropoietic changes induced by androgens
      are not mediated via its aromatization to estrogens.

PMID- 19159689
TI  - Cortical cell types and intermediate filament arrangements correlate with fiber
      curvature in Japanese human hair.
AB  - Naturally straight and curved human scalp hairs were examined using fluorescence
      and electron microscopy techniques to determine morphological and ultrastructural
      features contributing to single fiber curvature. The study excluded cuticle and
      medulla, which lack known bilateral structural asymmetry and therefore potential
      to form curved fibers. The cortex contained four classifiable cell types, two of
      which were always present in much greater abundance than the remaining two types.
      In straight hair, these cell types were arranged annularly and evenly within the
      cortex, implying that the averaging of differing structural features would
      maintain a straight fiber conformation. In curved fibers, the cell types were
      bilaterally distributed approximately perpendicular to fiber curvature direction
      with one dominant cell type predominantly located closest to the convex fiber
      side and the other, closest to the concave side. Electron tomography confirmed
      that the dominant cell type closest to the convex fiber side contained discrete
      macrofibrils composed of helically arranged intermediate filaments, while the
      dominant cell type closest to the concave side contained larger fused
      macrofibrils composed of intermediate filament arrangements varying from helical
      to hexagonal arrays approximately parallel to the longitudinal fiber axis. These
      findings concur with the current hypothesis of hair curvature formation and
      behavior.

PMID- 19159690
TI  - Quantitative examination of a novel clustering method using magnetic resonance
      diffusion tensor tractography.
AB  - MR diffusion tensor imaging (DTI) can measure and visualize organization of white
      matter fibre tracts in vivo. DTI is a relatively new imaging technique, and new
      tools developed for quantifying fibre tracts require evaluation. The purpose of
      this study was to compare the reliability of a novel clustering approach with a
      multiple region of interest (MROI) approach in both healthy and disease
      (schizophrenia) populations. DTI images were acquired in 20 participants (n=10
      patients with schizophrenia: 56+/-15 years; n=10 controls: 51+/-20 years) (1.5 T
      GE system) with diffusion gradients applied in 23 non-collinear directions,
      repeated three times. Whole brain seeding and creation of fibre tracts were then
      performed. Interrater reliability of the clustering approach, and the MROI
      approach, were each evaluated and the methods compared. There was high spatial
      (voxel-based) agreement within and between the clustering and MROI methods.
      Fractional anisotropy, trace, and radial and axial diffusivity values showed high
      intraclass correlation (p<0.001 for all tracts) for each approach. Differences in
      scalar indices of diffusion between the clustering and MROI approach were
      minimal. The excellent interrater reliability of the clustering method and high
      agreement with the MROI method, quantitatively and spatially, indicates that the
      clustering method can be used with confidence. The clustering method avoids
      biases of ROI drawing and placement, and, not limited by a priori predictions,
      may be a more robust and efficient way to identify and measure white matter
      tracts of interest.

PMID- 19159692
TI  - The Visual Evoked Potential is independent of surface alpha rhythm phase.
AB  - A Visual Evoked Potential (VEP) is an electrical signal picked up by a surface
      electrode in response to the activation of visual cortex by a visual stimulus.
      Because the VEP is typically much smaller in magnitude than the ongoing
      spontaneous EEG signal, the VEP is derived by averaging a large number of
      responses time-locked to stimulus presentation. Standard theory has it that the
      VEP is independent of the ongoing EEG, however, there has long been a competing
      view that the VEP is caused by a partial phase reset of the spontaneous alpha
      rhythm. We calculated the VEP where stimuli were presented at four different
      phases of the ongoing alpha rhythm, and subtracted away the responses to null
      trials synchronized to the same alpha rhythm phases, creating estimates of the
      VEP as a function of ongoing alpha rhythm phase. For some subjects there was
      evidence of an interaction between the VEP and the phase of the ongoing alpha
      rhythm, but this was idiosyncratic between subjects and conditions, and mostly
      evident in a later period when the VEP magnitude was very small. However, in
      general the VEP is independent of the phase of the ongoing alpha rhythm, and
      hence cannot be primarily caused by a partial phase resetting of the spontaneous
      EEG. It is possible that the VEP is either a phase-reset of an ongoing
      oscillation, or an oscillation induced by the sudden onset of a stimulus, but it
      cannot be the same oscillation as the surface alpha.

PMID- 19159691
TI  - Expectancy and treatment interactions: a dissociation between acupuncture
      analgesia and expectancy evoked placebo analgesia.
AB  - Recent advances in placebo research have demonstrated the mind's power to alter
      physiology. In this study, we combined an expectancy manipulation model with both
      verum and sham acupuncture treatments to address: 1) how and to what extent
      treatment and expectancy effects - including both subjective pain intensity
      levels (pain sensory ratings) and objective physiological activations (fMRI) -
      interact; and 2) if the underlying mechanism of expectancy remains the same
      whether placebo treatment is given alone or in conjunction with active treatment.
      The results indicate that although verum acupuncture+high expectation and sham
      acupuncture+high expectation induced subjective reports of analgesia of equal
      magnitude, fMRI analysis showed that verum acupuncture produced greater fMRI
      signal decrease in pain related brain regions during application of calibrated
      heat pain stimuli on the right arm. We believe our study provides brain imaging
      evidence for the existence of different mechanisms underlying acupuncture
      analgesia and expectancy evoked placebo analgesia. Our results also suggest that
      the brain network involved in expectancy may vary under different treatment
      situations (verum and sham acupuncture treatment).

PMID- 19159693
TI  - Effects of acute nicotine on brain function in healthy smokers and non-smokers:
      estimation of inter-individual response heterogeneity.
AB  - The present study used functional magnetic resonance imaging (fMRI) to
      investigate the neural mechanisms of nicotine effects on antisaccades (an
      oculomotor measure of the conflict between a reflexive response and a spatially
      complex volitional response) and prosaccades (involving reflexive overt
      attentional shifts). Given the known inter-individual variability in drug
      response we aimed to identify oculomotor variables and brain areas in which
      significant inter-individual heterogeneity in response to nicotine is observed.
      To do so we calculated within-session intraclass correlation (ICC) coefficients
      over measurements obtained before and after nicotine/placebo administration and
      reasoned that a significant reduction in ICC with nicotine compared to placebo
      would reflect the operation of significant inter-individual response
      heterogeneity. Thirteen light-to-moderate smokers and 11 non-smokers completed
      fMRI during antisaccades before and after subcutaneous injection of 12 microg/kg
      nicotine or saline placebo in a double-blind, randomised, cross-over design. All
      participants were healthy, right-handed males. Nicotine and placebo were given on
      separate occasions approximately 1 week apart with time of injection kept
      constant. Nicotine significantly reduced antisaccade latencies in both groups. At
      the level of brain function, during antisaccades the blood oxygen level dependent
      (BOLD) response in the left frontal eye field was non-significantly reduced by
      nicotine while it significantly increased following placebo in non-smokers, but
      there was no discernible effect in smokers. During prosaccades, it was found that
      deactivation areas (posterior cingulate gyrus and precuneus; right superior
      temporal gyrus) showed enhanced deactivations following nicotine administration
      in both groups. ICC analysis identified significant inter-individual response
      heterogeneity in antisaccade reflexive errors in smokers, and in a number of
      brain regions, particularly in non-smokers. These findings suggest that nicotine
      has beneficial effects at the cognitive level and leads to reductions in task
      related activations and further decreases of BOLD in deactivation areas. The
      comparison of within-session ICCs across drug conditions suggests that the
      effects of nicotine are subject to inter-individual variability at behavioural
      and neural levels.

PMID- 19159694
TI  - Combined use of non-invasive techniques for improved functional localization for
      a selected group of epilepsy surgery candidates.
AB  - Invasive cortical mapping is conventionally required for preoperative
      identification of epileptogenic and eloquent cortical regions before epilepsy
      surgery. The decision on the extent and exact location of the resection is always
      demanding and multimodal approach is desired for added certainty. The present
      study describes two non-invasive preoperative protocols, used in addition to the
      normal preoperative work-up for localization of the epileptogenic and
      sensorimotor cortical regions, in two young patients with epilepsy.
      Magnetoencephalography (MEG) was used to determine the primary somatosensory
      cortex (S1) and the ictal onset zones. Navigated transcranial magnetic
      stimulation (nTMS) was used to determine the location and the extent of the
      primary motor representation areas. The localization results from these non
      invasive methods were used for guiding the subdural grid deployment and later
      compared with the results from electrical cortical stimulation (ECS) via subdural
      grids, and validated by surgery outcome. The results from MEG and nTMS
      localizations were consistent with the ECS results and provided improved spatial
      precision. Consistent results of our study suggest that these non-invasive
      methods can be added to the standard preoperative work-up and may even hold a
      potential to replace the ECS in a subgroup of patients with epilepsy who have the
      suspected epileptogenic zone near the sensorimotor cortex and seizures frequent
      enough for ictal MEG.

PMID- 19159695
TI  - Evolution and pathogenesis of Leptospira spp.: lessons learned from the genomes.
AB  - Leptospirosis has emerged to become a major public health problem in developing
      countries. The availability of complete sequences of strains representing
      saprophytic and pathogenic species of the genus Leptospira is providing insights
      into the evolution of virulence and survival mechanisms used by these bacteria to
      persist in different ecological niches.

PMID- 19159696
TI  - Crucial role for LKB1 to AMPKalpha2 axis in the regulation of CD36-mediated long
      chain fatty acid uptake into cardiomyocytes.
AB  - Enhanced contractile activity increases cardiac long-chain fatty acid (LCFA)
      uptake via translocation of CD36 to the sarcolemma, similarly to increase in
      glucose uptake via GLUT4 translocation. AMP-activated protein kinase (AMPK) is
      assumed to mediate contraction-induced LCFA utilization. However, which catalytic
      isoform (AMPKalpha1 versus AMPKalpha2) is involved, is unknown. Furthermore, no
      studies have been performed on the role of LKB1, a kinase with AMPKK activity, on
      the regulation of cardiac LCFA utilization. Using different mouse models
      (AMPKalpha2-kinase-dead, AMPKalpha2-knockout and LKB1-knockout mice), we tested
      whether LKB1 and/or AMPK are required for stimulation of LCFA and glucose
      utilization upon treatment of cardiomyocytes with compounds
      (oligomycin/AICAR/dipyridamole) which induce CD36 translocation similar to that
      seen upon contraction. In AMPKalpha2- kinase-dead cardiomyocytes, the stimulating
      effects of oligomycin and AICAR on palmitate and deoxyglucose uptake and
      palmitate oxidation were almost completely lost. Moreover, in AMPKalpha2- and
      LKB1-knockout cardiomyocytes, oligomycin-induced LCFA and deoxyglucose uptake
      were completely abolished. However, the stimulatory effect of dipyridamole on
      palmitate uptake and oxidation was preserved in AMPKalpha2-kinase-dead
      cardiomyocytes. In conclusion, in the heart there is a signaling axis consisting
      of LKB1 and AMPKalpha2 which activation results in enhanced LCFA utilization,
      similarly to enhanced glucose uptake. In addition, an unknown dipyridamole
      activated pathway can stimulate cardiac LCFA utilization by activating signaling
      components downstream of AMPK.

PMID- 19159698
TI  - Characterization and anti-tumor activity of alkali-extracted polysaccharide from
      Enteromorpha intestinalis.
AB  - The polysaccharide DAEB was isolated and purified from Enteromorpha intestinalis.
      It consisted of rhamnose, xylose, galactose, and glucose in a molar ratio of
      5.36:1.00:0.57:0.64, and had a molecular weight of 46.8 kDa. Mice were treated
      with three doses of DAEB for 10 consecutive days by oral administration, the
      tumor inhibition was 61.17%, 67.65% and 70.59% at doses of 100, 200 and 400
      mg/kg, respectively. However, no direct cytotoxicity was detected. At dose of
      100, 200 and 400 mg/kg, a significant increase (P<0.01) in relative spleen and
      thymus weight, and production of tumor necrosis factor alpha (TNF-alpha) were
      observed in DAEB treated groups. We also found that DAEB significantly stimulated
      lymphocyte proliferation, especially Concanavalin A-induced lymphocyte
      proliferation in a dose-dependent manner, and augmented phagocytosis and
      secretion of NO and TNF-alpha in peritoneal macrophages. The results indicated
      that DAEB had potent anti-tumor activity which may be associated with its potent
      immunostimulating effect.

PMID- 19159697
TI  - Bmp7 expression and null phenotype in the urogenital system suggest a role in re
      organization of the urethral epithelium.
AB  - Signaling by Bone morphogenetic proteins (Bmps) has multiple and diverse roles in
      patterning and morphogenesis of the kidney, eye, limbs and the neural tube. Here,
      we employed the Bmp7(lacZ) strain to perform a detailed analysis of Bmp7
      expression and the null phenotype during development of the mouse urogenital
      system. The urethral compartment originates in mid-embryogenesis from the ventral
      part of the cloaca, a transient cavity at the caudal end of the hindgut. At mid
      gestation, Bmp7 expression was detected within several specific domains in the
      cloacal epithelium and mesenchyme. In late embryogenesis, Bmp7 expression was
      present in the urethra, rectum, the urethral glands, corpus cavernosum, and in
      the male and female genital ducts. Importantly, loss of Bmp7 resulted in arrest
      in cloacal septation, and severe defects in morphogenesis of the genital urethra
      and mesenchyme. Together, our analysis of Bmp7 expression and the null phenotype,
      indicates that Bmp7 may play an important role in re-organization of the
      epithelium during cloacal septation and morphogenesis of the genital tubercle.

PMID- 19159699
TI  - Immunodominant role of CCHA subunit of Concholepas hemocyanin is associated with
      unique biochemical properties.
AB  - Hemocyanin, the oxygen transporter metallo-glycoprotein from mollusks, shows
      strong relationship between its notable structural features and intrinsic
      immunomodulatory effects. Here we investigated the individual contribution of
      CCHA and CCHB subunits from Concholepas hemocyanin (CCH) to in vivo humoral
      immune response and their pre-clinical evaluation as immunotherapeutic agent in a
      mice bladder cancer model, in relation to their biochemical properties. To this
      end, subunits were purified and well characterized. Homogeneous subunits were
      obtained by anionic exchange chromatography, and its purity assessed by
      electrophoretic and immunochemical methods. While each CCH subunit contains eight
      functional units showing partial cross reaction, the vibrational spectral
      analysis showed several spectral differences, suggesting structural differences
      between them. In addition, we demonstrated differences in the carbohydrate
      content: CCHA had a 3.6% w/w sugar with both N- and O-linked moieties. In turn,
      CCHB had a 2.5% w/w sugar with N-linked, while O-linked moieties were nearly
      absent. Considering these differences, it was not possible to predict a priori
      whether the immunogenic and immunotherapeutic properties of subunits might be
      similar. Surprisingly, both subunits by itself induced a humoral response, and
      showed an antitumor effect in the bladder carcinoma cell line MBT-2. However,
      when immunologic parameters were analyzed, CCHA showed better efficiency than
      CCHB. No allergic reactions or any toxic effects were observed in mice treated
      with CCHA, sustaining its potential therapeutic use. Our study supports that CCHA
      subunit accounts for the most important features involved in the immunogenicity
      of CCH, such as better hydrophilicity and higher content of carbohydrates.

PMID- 19159700
TI  - Functional fusion mutant of Candida antarctica lipase B (CalB) expressed in
      Escherichia coli.
AB  - Candida antarctica lipase B (CalB) was functionally expressed in the cytoplasm of
      Escherichia coli Origami(DE3) with the N-terminus fusion of E. coli endogenous
      proteins. The previously-identified stress responsive proteins through
      comparative proteome analyses such as malate dehydrogenase (Mdh),
      spermidine/putrescine-binding periplasmic protein (PotD), and FKBP-type peptidyl
      prolyl cis-trans isomerase (PPIases) (SlyD) dramatically increased the solubility
      of CalB in E. coli cytoplasm when used as N-terminus fusion partners. We
      demonstrated that Mdh, PotD, and SlyD were powerful solubility enhancers that
      presumably facilitated the protein folding of CalB. Moreover, among the various
      fusion mutants, Mdh-CalB showed the highest hydrolytic activity and was as
      biologically active as standard CalB. Similarly to the previous report, the
      electrophoretic properties of CalB indicate that CalB seems to form dimer-based
      oligomer structures. We evaluated the structural compatibility between the fusion
      partner protein and CalB, which seems to be of crucial importance upon the
      bioactive dimer formation of CalB and might affect the substrate accessibility to
      the enzyme active site, thereby determining the biological activities of the
      fusion mutants.

PMID- 19159701
TI  - Critical issues of PTH assays in CKD.
AB  - Measurement of bioactive parathyroid hormone (PTH) is essential for the optimal
      management of secondary hyperparathyroidism and its associated bone disorders in
      chronic kidney disease (CKD) patients. For this purpose, three generations of
      increasingly specific PTH assays have been developed over the last 4 decades. To
      date, however, only second-generation PTH assays are most widely used, although
      these have been shown to cross-react with large PTH fragments having a partially
      preserved N-structure, mostly PTH(7-84). The newly developed third-generation PTH
      assays are believed to be the most specific means of measuring PTH(1-84), but
      their clinical utility remains debatable. More recently, these latter assays have
      also been shown to react with a new N-form of PTH, which has been identified in
      patients with severe hyperparathyroidism and parathyroid carcinoma. Progressive
      research in this area has advanced our understanding considerably regarding the
      circulating molecular forms of PTH and their pathophysiological roles in bone
      abnormalities associated with CKD. However, developing an ideal PTH assay
      continues to be difficult because of key issues such as the reliability of PTH as
      a surrogate marker for bone turnover, practicality of employing third-generation
      PTH assays, and unknown biological implications of N-PTH and other PTH fragments.
      Further research exploring these issues is mandatory to understand and optimally
      manage parathyroid disorders and bone abnormalities in CKD patients.

PMID- 19159702
TI  - Laparoscopic diagnosis and treatment of a phenotypic girl with mosaic
      45,XO/46,X,idic(Y) mixed gonadal dysgenesis.
AB  - We report our experience with laparoscopic gonadal biopsy and gonadectomy for a
      girl with a dicentric Y chromosome in mixed gonadal dysgenesis (MGD). A 4-year
      old phenotypic girl was referred to our hospital because of slight enlargement of
      the clitoris. Fluorescence in situ hybridization analysis with Y chromosome
      specific probes showed a karyotype with 45,XO/46,X,+idic(Y)(p11.32) and presence
      of the sex-determining region Y sequence. The pathologic finding by frozen
      section technique using laparoscopic biopsy specimens during the operation
      demonstrated a left streak gonad and right testis, and she was diagnosed with
      MGD. Finally, we performed laparoscopic bilateral gonadectomy. Laparoscopic
      management is a good approach for patients with sexual development disorders,
      including MGD because it provides minimally invasive surgery for children and
      enables all necessary procedures, including evaluation, biopsy, and gonadectomy,
      for diagnosis and treatment.

PMID- 19159703
TI  - Didelphic uterus and obstructed hemivagina resulting in obstructed hydronephrosis
      of transplanted kidney.
AB  - Uterine didelphys are rare malformations involving the Mullerian ducts. The
      incidence ranges from 0.1% to 3.8%. This wide range could be because of
      inaccurate diagnosis or to the fact that many of these diagnoses are not detected
      during the women's lifetime. Here, we report the management of a 16-year-old
      female patient who had uterine didelphys with obstructed hemivagina, resulting in
      obstructive hydronephrosis in her transplanted kidney.

PMID- 19159704
TI  - A ganglioneuroma of the sigmoid colon presenting as leading point of
      intussusception in a child: a case report.
AB  - We present a case of intestinal ganglioneuroma (GN) of the sigmoid colon in a 5
      year-old girl, which caused intermittent colocolic intussusception.
      Ganglioneuromas are rare benign tumors of the autonomic nervous system composed
      of mature ganglion cells and satellite cells. Colonic GNs are uncommon. The
      unusual intramural proliferation of neural elements in this case resembled the
      diffuse intestinal ganglioneuromatosis, which is known to be associated with
      multiple endocrine neoplasia type 2B. However, the specific mutations of multiple
      endocrine neoplasia type 2B were not found by genetic sequencing. This is the
      first pediatric case described in the literature of a solitary polypoid GN
      presenting as a colocolic intussusception. We present a brief overview of
      intestinal ganglioneuromatous lesions and associated conditions.

PMID- 19159705
TI  - Idiopathic thrombocytopenic purpura complicated with biliary atresia: a rare
      occurrence and literature review.
AB  - The association of biliary atresia (BA) and idiopathic thrombocytopenic purpura
      (ITP) is extremely rare, with only 2 cases being reported in the literature. This
      report describes the very rare case of a 1-year-old boy with BA complicated with
      ITP after cholangitis and the successful steroid treatment of ITP. We review the
      literature on this type of relationship between BA and ITP and discuss the
      clinical features of this complication. Furthermore, the possible cause of the
      onset of ITP complicated with BA was explored in this report.

PMID- 19159706
TI  - Congenital subglottic web: a rare cause of neonatal stridor.
AB  - Laryngeal web is a rare malformation caused by an anomalous embryologic
      development of the primitive larynx. Most of the reported cases are of the
      glottic type; the subglottic web is extremely rare. Laryngotracheobronchoscopy
      plays an essential role in the diagnostic workup of this lesion, and
      endolaryngeal resection is the preferred treatment whenever a structural
      cartilaginous subglottic stenosis is not present. The authors present the case of
      a neonate with a subglottic web diagnosed soon after birth. Management of this
      rare entity is discussed.

PMID- 19159707
TI  - Simultaneous costal cartilage-sparing modified Ravitch procedure and latissimus
      dorsi transfer for chest wall deformity repair in Poland's syndrome.
AB  - Poland's syndrome is a constellation of rare congenital anomalies that include
      hypoplasia of breast and underlying subcutaneous tissue, absence of the
      costosternal portion of the pectoralis major muscle, deformity or absence of
      ribs, absence of axillary hair, and syndactyly. Various surgical techniques have
      been described to repair such chest wall defects. We report a case of
      simultaneous Fonkalsrud procedure (costal cartilage-sparing version of the
      modified Ravitch procedure) and latissimus dorsi transfer in a 15-year-old boy
      with Poland's syndrome. The Fonkalsrud procedure has been used in the repair of
      pectus excavatum and pectus carinatum, and latissimus dorsi muscle transfer has
      been used in the repair of Poland's syndrome. In this report, we describe their
      combined use in an adolescent with severe pectus excavatum associated with
      Poland's syndrome. This combination of established operations resulted in a
      successful outcome.

PMID- 19159708
TI  - Stone-containing periampullary duodenal duplication cyst with aberrant pancreatic
      duct.
AB  - This case report describes a unique variant of a duodenal duplication cyst in an
      8-year-old boy who had recurrent episodes of upper abdominal pain. Imaging
      revealed a stone-containing cyst near the biliaropancreatic ducts and concomitant
      hydrops of the gallbladder. Open transduodenal marsupialization of the cyst and
      resection of the inflamed gallbladder were performed. Further episodes of
      pancreatitis did not occur for a follow-up of 2 years.

PMID- 19159709
TI  - Ulcerative colitis with severe backwash ileitis successfully treated by staged
      operation without sacrificing any involved ileum.
AB  - Extension of the inflammatory process to the terminal portion of the ileum in
      patients with ulcerative colitis is commonly known as backwash ileitis (BWI). To
      the best of our knowledge, few studies of severe BWI have been reported in the
      English literature, and surgical strategies for this disease have not been
      discussed. We report 2 patients with ulcerative colitis and severe BWI, with
      concomitant ileal bleeding and perforation. In both cases, staged operation
      without sacrificing the involved area of the terminal ileum led to ileal pouch
      anal anastomosis, with a favorable postoperative outcome. Our cases suggest that
      the underlying pathophysiologic conditions in BWI may be reversible, and the
      involved lesion can be salvaged in some cases.

PMID- 19159710
TI  - Castleman disease: surgical cure in pediatric patients.
AB  - Castleman disease is a rare disorder characterized by lymphoid hyperplasia which
      rarely manifests in children. We present 2 cases which highlight both histologic
      variants of this disease, and provide suggestions regarding workup and treatment
      with the goal of making practitioners aware of Castleman disease in the
      differential diagnosis of a child presenting with vague symptoms.

PMID- 19159711
TI  - Mosaic trisomy 22 associated with total colonic aganglionosis and malrotation.
AB  - AIMS: Abnormalities of chromosome 22 karyotype have been reported to be
      associated with both malrotation and aganglionosis. However, although malrotation
      has been reported to occur in the rare mosaic trisomy 22, Hirschsprung's disease
      has not. We present a case of mosaic trisomy 22 that presented during the
      neonatal period with malrotation and total colonic aganglionosis, and we discuss
      the possible pathogenesis of both conditions in the light of this rare genetic
      abnormality. The association of total colonic aganglionosis and mosaic trisomy 22
      has not previously been reported. RESULTS: A male neonate with an antenatal
      diagnosis of de novo mosaic trisomy 22 underwent a laparotomy with correction of
      malrotation and midgut volvulus on day 3 of life. Rectal biopsy was performed
      because he had not passed meconium. This revealed Hirschsprung's disease; an
      ileostomy was formed, and histology confirmed aganglionosis as far as the
      terminal ileum. At 6 months, a modified Lester Martin Duhamel pull-through was
      performed. He is showing normal development at follow-up. CONCLUSIONS: We
      recommend an increased index of suspicion of Hirschsprung's disease and
      malrotation in patients with mosaic trisomy 22 until further evidence can
      establish or exclude a meaningful relationship.

PMID- 19159712
TI  - The innovation of success: the pediatric surgery and APSA response to "disruptive
      technologies".

PMID- 19159713
TI  - Creativity and the surgeon.
AB  - This Robert E. Gross lecture is an analysis of the concept of creativity and how
      it relates to the practice of surgery. The questions-why surgery and creativity
      are closely associated; what influences creativity; why we should be concerned
      about it; and, finally, what rewards it brings-are discussed. In a personal note,
      the author describes his approach to creativity, with simplification as a central
      theme. He presents 6 examples of his work and the lessons learned from this
      activity. He stresses the importance of fostering creativity in all institutions
      in which physicians are trained and the need to focus on medical students,
      residents, and fellows. The critical importance of identifying, nurturing, and
      protecting innovators, as well as the role of the mentor, is emphasized. Because
      creativity has a place in many settings and discovery encompasses a wide
      spectrum, the author provides multiple suggestions aimed at encouraging the
      participation of those providing surgical care in the fulfilling experience of
      creative activity and innovation.

PMID- 19159714
TI  - Inventing our future: training the next generation of surgeon innovators.

PMID- 19159715
TI  - Technical innovation, standardization, and skill qualification for pediatric
      minimally invasive surgery in Japan.
AB  - This is a presentation of sharing endeavors at modifying and standardizing
      surgical procedures as well as establishing endoscopic surgical skill
      qualification in the field of pediatric surgery in Japan.

PMID- 19159716
TI  - What's New in Pediatric Surgery.
AB  - This is a reflection on 2 people who have had a profound influence on many lives
      and a review of changes in pediatric surgery.

PMID- 19159717
TI  - Development of an artificial placenta I: pumpless arterio-venous extracorporeal
      life support in a neonatal sheep model.
AB  - PURPOSE: Effective treatment of respiratory failure in premature infants remains
      an unsolved problem. The development of an artificial placenta, in the form of a
      pumpless arteriovenous extracorporeal life support (AV-ECLS) circuit that
      maintains fetal circulation, is an appealing alternative. METHODS: A near-term
      (140 d/term = 145 days) neonatal lamb model was used (n = 7). Fetuses were
      exposed by hysterotomy, and flow probes were placed on the ductus arteriosus,
      aorta, and carotid artery. Catheters were placed into the umbilical vessels, and
      pumpless AV-ECLS was initiated. Fetuses were submerged in a warm saline bath, and
      support was maintained for up to 4 hours. RESULTS: Mean initial device flow was
      383 mL/min but steadily declined to 177 mL/min at 4 hours. Mean initial pO(2) was
      24 mm Hg and 18 mm Hg at 4 hours. Initial mean pCO(2) was 60 mm Hg and declined
      to 42 mm Hg at 4 hours. Mean arterial pressure was initially 43 mm Hg and
      decreased to 34 mm Hg at 4 hours. Flow in the ductus arteriosus was maintained
      for 4 hours. Of 7 fetuses, 5 survived 4 hours of support. CONCLUSIONS: Pumpless
      AV-ECLS can support gas exchange and maintain fetal circulation in a neonatal
      lamb model for a 4-hour period. Prolonged support (>4 hours) is hampered by high
      cannula resistance and declining device flow.

PMID- 19159718
TI  - High-risk fetal congenital pulmonary airway malformations have a variable
      response to steroids.
AB  - BACKGROUND/PURPOSE: Anecdotal reports suggest that maternal steroids may arrest
      the growth of congenital pulmonary airway malformations (CPAMs), preventing or
      reversing hydrops. We reviewed our experience with CPAMs to determine the fetal
      response to steroid therapy. METHODS: This study is a retrospective review of all
      fetal CPAMs from 2004 to 2008. Fetuses with high-risk CPAMs that received at
      least one course of steroids were identified. Fetal magnetic resonance imaging
      and ultrasound data were used to classify the CPAMs, identify hydrops fetalis and
      follow the fetuses poststeroid dosing. RESULTS: Forty-four fetuses with CPAM were
      identified. Fifteen patients were found to have received at least one course of
      steroids. Thirteen were hydropic and 2 were nonhydropic. Seven of the 13 hydropic
      fetuses (54%) showed an initial response to steroid administration, whereas the 2
      nonhydropic high-risk fetuses progressed to birth without developing hydrops.
      Seven of the 15 patients, however, resulted in fetal demise or early postnatal
      death, giving a survival rate of 53%. CONCLUSIONS: High-risk CPAMs have a
      variable response to steroids. This variable response demonstrates the need for a
      placebo-controlled randomized study to more accurately determine the effect of
      steroids on hydrops and CPAM growth rates. Repeated steroid courses may not be
      helpful, and progression in CPAM volume to head circumference ratio (CVR) or
      hydrops should prompt open fetal surgery to prevent irreversible fetal insult.

PMID- 19159719
TI  - Survival after laser surgery for twin-to-twin transfusion syndrome: when are they
      out of the woods?
AB  - PURPOSE: Severe, progressive twin-to-twin transfusion syndrome (TTTS) is
      associated with near-100% mortality if left untreated. Endoscopic laser ablation
      of placental vessels (ELA) is associated with 75% to 80% survival of at least one
      twin. The actuarial risk of fetal demise after ELA has not yet been described.
      STUDY DESIGN: A retrospective cohort study from 2 centers on a consecutive series
      of 163 sets of monochorionic twins with severe TTTS (18 Quintero stage I, 55
      stage II, 71 stage III, 19 stage IV) who underwent ELA. Actuarial survival was
      calculated and stratified for donor vs recipient and according to stage. RESULTS:
      Median gestational age at diagnosis was 20.1 weeks; median operative time was 60
      minutes. Overall survival was 63%, and survival of at least one twin was seen in
      76% of pregnancies. Of fetal demises, 10% occurred within 48 hours after ELA, and
      90% of all fetal demises occurred within 1 month. There was a 10% survival
      advantage of recipients over donors. Survival was similar for stages I, II, and
      IV (75%-80%), compared with 55% for stage III. CONCLUSIONS: Actuarial survival
      curves for TTTS confirms a greater burden on donor than on recipient but not at a
      previously reported 2:1 ratio. The current staging system does not accurately
      reflect post-ELA mortality risk. The unexpected higher mortality in stage III may
      reflect a more acute progression of the disorder in this group, an adverse effect
      of LA on an as yet unknown subgroup with stage III or, alternatively,
      preoperative demise of fulminant stage IV patients, leaving a stage IV subgroup
      with a more benign course and better outcome.

PMID- 19159720
TI  - Neonatal outcomes associated with intestinal abnormalities diagnosed by fetal
      ultrasound.
AB  - PURPOSE: Intestinal abnormalities are sometimes seen during antenatal testing;
      however, the postnatal importance of these findings has not been well
      established. We evaluated whether abnormal intestinal appearance on fetal
      ultrasound (US) was ultimately related to neonatal outcome. METHODS: Fetal US
      examinations from 2003 to 2006 were evaluated. Hyperechogenic bowel was defined
      as having the echogenicity comparable to bone, and dilated bowel was identified
      based on the sonographer's assessment. Persistence or resolution of US findings
      on subsequent US examinations and eventual outcomes were assessed. Cases were
      categorized as hyperechogenic or dilated and then subgrouped based on whether the
      US finding resolved. RESULTS: Sixty-eight fetuses had either hyperechogenic (n =
      48) or dilated bowel (n = 20) on antenatal US. In 56 cases, complete data were
      available for analysis. Of 44 liveborn infants, 11 (25.0%) had an abdominal
      abnormality, and 33 (75.0%) were normal at birth. Compared to those with dilated
      bowel, fetuses with hyperechogenic bowel had a higher rate of prenatal demise
      (20.8% vs 10%) but a lower rate of abnormality at birth (10.3% vs 53.3%).
      Hyperechogenic bowel resolved on subsequent US more frequently than dilated bowel
      (65.5% vs 20.0%). In both groups, all fetuses with sonographic resolution were
      normal at birth. Of 9 fetuses that had persistently hyperechogenic bowel, 3
      (33.3%) were born with an abnormality, and all were found to have meconium
      peritonitis or meconium ileus. In the 12 cases where dilated bowel did not
      resolve, 8 (66.7%) were eventually born with an abnormality, most commonly
      intestinal atresia. CONCLUSIONS: Hyperechogenic and dilated bowel are associated
      with a significant rate of fetal demise. Hyperechogenicity is more common than
      dilation and is more likely to be transient. Dilated bowel is more often
      associated with neonatal abnormality than hyperechogenic bowel. Persistence of
      fetal US findings predicts a higher likelihood of abnormality in the neonate.

PMID- 19159721
TI  - Differential risk for neonatal surgical airway intervention in prenatally
      diagnosed neck masses.
AB  - PURPOSE: We aimed to identify risk factors for neonatal surgical airway
      intervention among fetuses with prenatally diagnosed cervical masses. METHODS: An
      8-year retrospective review identified 23 consecutive patients with a prenatal
      diagnosis of a neck mass, managed at a single tertiary center. Variables analyzed
      included anticipated diagnosis, extent of the mass, need for any surgical airway
      intervention in the neonatal period, final histopathology data, and survival.
      Statistical analysis was based on the Fisher and Fisher-Freeman-Halton exact
      tests (significance set at P < or = .05) and exact 95% confidence intervals for
      risk differences. RESULTS: Eight patients underwent termination of pregnancy or
      were lost to follow-up. The imaging-based prenatal diagnosis was confirmed
      postnatally in 93% (14/15) of the remaining patients. Final diagnoses included
      lymphatic malformation (8), teratoma (6), and esophageal duplication (1).
      Teratomas were associated with a significantly higher risk for neonatal airway
      intervention than lymphatic malformations (67% vs 11%, P = .02). The majority of
      such procedures were performed under ex utero intrapartum treatment. Survival was
      93% (14/15). CONCLUSIONS: Cervical teratomas are significantly more likely to
      demand surgical airway intervention in the neonate, typically under ex utero
      intrapartum treatment, than cervical lymphatic malformations. These findings
      should be considered in the prenatal counseling for fetal cervical masses.

PMID- 19159722
TI  - Analysis of 29 consecutive thoracoscopic repairs of congenital diaphragmatic
      hernia in neonates compared to historical controls.
AB  - PURPOSE: The applicability of minimally invasive surgical techniques to pediatric
      surgical diseases continues to grow. Surgeons have hesitated to apply these
      methods to congenital diaphragmatic hernia (CDH) of Bochdalek because of the
      disease-associated pulmonary hypertension and patient fragility. We began
      performing thoracoscopic repair (CDH-T) in 2004 and have since completed 29
      sequential repairs. To evaluate feasibility and outcomes, we compared this
      experience to a historical control group who underwent open repair (CDH-O) at the
      same institution by the same surgeons from 2001 to 2004. METHODS: From January
      2001 through November 2007, 72 neonates were evaluated jointly by the Neonatology
      and Pediatric Surgical services for CDH. Fifteen infants died before any
      corrective operation and were excluded from analysis. Demographics including
      gestational age, birth weight, Apgar scores, percent outborn, usage of
      extracorporeal life support, and associated anomalies were recorded. End points
      were complications, additional operative procedures, initial patch closure,
      recurrence, length of stay in non-extracorporeal membrane oxygenation patients,
      and postoperative mortality. RESULTS: Demographic characteristics were similar
      between the 2 groups. There were no statistically significant differences in
      complications (71.5% vs 55%, P = .28), additional related operative procedures
      (42.9% vs 34.5%, P = .59), use of prosthetic patch (42.8% vs 51.7%, P = .60),
      recurrence (6.9% vs 20.7%, P = .25), length of stay (24 vs 34 days, P = .11), or
      postoperative mortality (21.4% vs 6.9%, P = .14) between the CDH-O and CDH-T
      groups, respectively. There was one conversion in the CDH-T group (3.4%).
      CONCLUSIONS: To our knowledge, this is the largest reported series of CDH-T of
      neonatal CDH of Bochdalek. We have demonstrated the feasibility of performing
      this procedure thoracoscopically in an unselected population including children
      who have undergone prior extracorporeal life support. These results compare
      favorably with CDH-O, although further follow-up is required to determine the
      durability of the approach.

PMID- 19159723
TI  - Identifying neonates at a very high risk for mortality among children with
      congenital diaphragmatic hernia managed with extracorporeal membrane oxygenation.
AB  - PURPOSE: The purpose of this study was to identify mortality risk factors in
      children with congenital diaphragmatic hernia (CDH) treated with extracorporeal
      membrane oxygenation (ECMO) and generate a prediction score for those at a very
      high risk for mortality. METHODS: Data on first ECMO runs of all neonates with
      CDH, between January 1997 and June 2007, were obtained from the Extracorporeal
      Life Support Organization registry (N = 2678). The data were split into "training
      data (TD)" (n = 2006) and "validation data" (n = 672). The primary outcome
      analyzed was in-hospital mortality. Modified Poisson regression was used for
      analyses. RESULTS: Overall in-hospital mortality among 2678 neonates (males, 57%;
      median age at ECMO, 1 day) was 52%. The univariate and multivariable analyses
      were performed using TD. An empirically weighted mortality prediction score was
      generated with possible scores ranging from 0 to 35 points. Of 69 who scored 14
      or higher in the TD, 62 died (positive predictive value [PPV], 90%), of 37 with
      15 or higher, 35 died (PPV, 95%), of 23 with 16 or higher, 22 died (PPV, 96%). A
      cut-off point of 15 was chosen and was tested using the separate validation
      dataset. In validation data, the cut-off point 15 had a PPV of 96% (23 died of
      24). CONCLUSION: Scoring 15 or higher on the prediction score identifies neonates
      with CDH at a very high risk for mortality among those managed with ECMO and
      could be used in surgical decision making and counseling.

PMID- 19159724
TI  - Evaluating cannulation strategies used during second courses of extracorporeal
      membrane oxygenation in a large cohort of pediatric patients.
AB  - PURPOSE: After a successful course of extracorporeal membrane oxygenation (ECMO),
      patients can deteriorate and a second ECMO course may be contemplated. When a
      second ECMO course becomes necessary in pediatric patients, survival rates
      comparable to the first ECMO course are possible. The perceived difficulties
      involved in recannulation after an initial ECMO course can prevent clinicians
      from reliably offering a second ECMO run to an eligible pediatric patient. We
      hypothesized that national ECMO registry data could provide cannulation templates
      for pediatric patients requiring a second ECMO course. METHODS: We obtained data
      from the Extracorporeal Life Support Organization registry (1981-2007) on
      patients 1 to 18 years old who required single-run ECMO (SRE) or multiple-run
      ECMO (MRE). Primary outcome measures were complications and survival. Cannulation
      specific variables were compared using chi(2) methods (Fisher exact, McNemar's).
      Statistical significance was assumed at P < .05. RESULTS: A total of 3810 (96.8%)
      children underwent SRE and 127 (3.2%) required MRE. Survival was similar in both
      groups (49% vs 44%; P = .28). Cannulation data were available in 2539 SRE (67%)
      and 88 MRE (69%) cases. Compared with SRE, first ECMO courses in MRE patients
      consisted of fewer cervical (52.3% vs 71.7%; P < .001) but more femoral (20.5% vs
      10.7%; P = .01) and central (27.3% vs 17.6%; P = .02) cannulations. In MRE
      patients, central cannulation was more frequent in second vs first ECMO courses
      (43.0% vs 27.3%; P = .03). Multiple-run ECMO survival was unaffected by
      cannulation strategy. Multiple-run ECMO patients with unchanged cannulation sites
      between first and second ECMO courses had fewer total complications than those
      requiring new cannulation sites (3.7 vs 5.1; P = .04). CONCLUSIONS: Second ECMO
      courses in pediatric patients can achieve survival comparable to the first
      course, but more often require central cannulation. Reusing cannulation sites for
      a second ECMO course is associated with fewer total complications than
      cannulating at new sites. These data provide guidance when considering
      cannulation strategies for second ECMO courses in pediatric patients.

PMID- 19159725
TI  - Congenital and acquired single-lung patients: long-term follow-up reveals high
      mortality risk.
AB  - PURPOSE: Single-lung patients are uncommon. Case reports suggest that these
      patients have significant morbidity and mortality risks because of associated
      anomalies, airway obstruction as well as decreased pulmonary reserve. This study
      was designed to review morbidity and mortality of single-lung patients. METHODS:
      A retrospective review of single-lung patients admitted to our hospital from
      January 1988 to June 2007. RESULTS: Twelve single-lung patients were treated in
      our hospital with mean follow-up of 22.9 months. Six congenital lung aplasia
      patients presented as neonates, with 2 diagnosed antenatally. Of 4 patients with
      respiratory distress, 3 required surgical interventions to correct airway
      symptoms. Three patients died before 9 months of age because of respiratory
      failure, sepsis, or cardiac arrest. The remaining survivors have minimal
      respiratory distress. There were 6 pneumonectomy patients as follows: 5 for
      malignancies and 1 for bronchiectasis. There were 2 deaths from recurrent
      disease. Four patients had respiratory symptoms with one patient requiring tissue
      expander insertion for the correction of airway torsion from mediastinal shift.
      CONCLUSIONS: The morbidity and mortality of infant single-lung patients are
      significant. Respiratory distress from decreased pulmonary reserve must be
      distinguished from airway obstruction because of mediastinal shift. Bronchoscopic
      assessment was invaluable to the diagnosis and management of these patients.

PMID- 19159726
TI  - Thoracoscopic decortication vs tube thoracostomy with fibrinolysis for empyema in
      children: a prospective, randomized trial.
AB  - PURPOSE: Management of empyema has been debated in the literature for decades.
      Although both primary video-assisted thoracoscopic surgery (VATS) and tube
      thoracostomy with pleural instillation of fibrinolytics have been shown to result
      in early resolution when compared to tube thoracostomy alone, there is a lack of
      comparative data between these modes of management. Therefore, we conducted a
      prospective, randomized trial comparing VATS to fibrinolytic therapy in children
      with empyema. METHODS: After Institutional Review Board approval, children
      defined as having empyema by either loculation on imaging or more than 10,000
      white blood cells/microL were treated with VATS or fibrinolysis. Based on our
      retrospective data using length of postoperative hospitalization as the primary
      end point, a sample size of 36 patients was calculated for an alpha of .5 and a
      power of 0.8. Fibrinolysis consisted of inserting a 12F chest tube followed by
      infusion of 4 mg tissue plasminogen activator mixed with 40 mL of normal saline
      at the time of tube placement followed by 2 subsequent doses 24 hours apart.
      RESULTS: At diagnosis, there were no differences between groups in age, weight,
      degree of oxygen support, white blood cell count, or days of symptoms. The
      outcome data showed no difference in days of hospitalization after intervention,
      days of oxygen requirement, days until afebrile, or analgesic requirements. Video
      assisted thoracoscopic surgery was associated with significantly higher charges.
      Three patients (16.6%) in the fibrinolysis group subsequently required VATS for
      definitive therapy. Two patients in the VATS group required ventilator support
      after therapy, one of whom required temporary dialysis. No patient in the
      fibrinolysis group clinically worsened after initiation of therapy. CONCLUSIONS:
      There are no therapeutic or recovery advantages between VATS and fibrinolysis for
      the treatment of empyema; however, VATS resulted in significantly greater
      charges. Fibrinolysis may pose less risk of acute clinical deterioration and
      should be the first-line therapy for children with empyema.

PMID- 19159727
TI  - Analysis of outcome in 298 extremely low-birth-weight infants with patent ductus
      arteriosus.
AB  - PURPOSE: Indomethacin is accepted therapy for patent ductus arteriosus (PDA) in
      ELBW infants (<1000 g). We hypothesize that surgical ligation may provide
      comparatively superior outcomes in select ELBW infants. METHODS: Predischarge
      outcomes of 298 ELBW infants with echocardiography-proven PDA were
      retrospectively compared by treatment provided: no treatment (group 1, n = 54),
      indomethacin (group 2, n = 140), ligation (group 3, n = 46), and ligation after
      indomethacin failure (group 4, n = 58). chi(2) and Wilcoxon rank sum tests were
      used to test for significance. Institutional review board approval was obtained
      (IRB/05-00395). RESULTS: Group 3 had significantly lower gestational age (P <
      .001), birth weight (P = .006), and 5-minute Apgar scores (P = .03) compared with
      group 2. Group 3 and group 1 had a higher rate of pretreatment intraventricular
      hemorrhage (IVH) compared with group 2 (P < .001). By contrast, posttreatment
      complications including acute renal failure, necrotizing enterocolitis,
      thrombocytopenia, and IVH occurred more frequently in groups 2 (P = .004) and 4
      (P = .001) compared with group 3. Survival was 57.7% in group 1 compared with
      groups 2, 3, and 4 (82.4%, 86.0%, and 92.7% respectively; P = .001). Preoperative
      conditions associated with nonsurvival include gestational age (P = .009), birth
      weight (P = .002), maternal preeclampsia (P = .015), 5-minute Apgar score (P =
      .013), and sepsis (P = .018). Posttreatment complications associated with
      nonsurvival include acute renal failure (P = .002), thrombocytopenia (P = .002),
      and necrotizing enterocolitis (P = .034). Survival was not influenced by any
      congenital comorbidity, pre- or posttreatment IVH, diameter of the PDA, or
      recurrence of the PDA after indomethacin therapy. CONCLUSIONS: (1) Patent ductus
      arteriosis requires treatment in ELBW infants to maximize survival. (2)
      Indomethacin and surgical ligation permit equivalent survival in low-risk ELBW
      infants, but indomethacin results in a high failure and complication rate
      requiring operative salvage in a number of patients. (3) Surgical ligation
      permits survival of high-risk ELBW infants with a low complication rate and is
      preferable to indomethacin in ELBW infants with the above risk factors.

PMID- 19159728
TI  - A 5-year experience with a minimally invasive technique for pectus carinatum
      repair.
AB  - PURPOSE: This report describes a 5-year experience with a novel, minimally
      invasive surgical technique for treatment of pectus carinatum. METHODS: From June
      2002 to August 2007, 40 patients underwent operation to correct pectus carinatum
      by pressure applied through a curved steel bar that was placed subcutaneously
      anterior to the sternum, via lateral thoracic incisions. The bar is inserted
      through a polyvinyl chloride tube with the convexity facing posteriorly. The
      polyvinyl chloride tube is positioned presternally by trocar. Subperiosteal wires
      attach small fixation plates to the ribs laterally, and the convex bar is secured
      to the small fixation plates with screws applying manual pressure to the anterior
      chest wall until the desired configuration is achieved. The compressive elongated
      bar is attached to the fixation plate with screws. The average age was 14.3 years
      (range, 10-21 years), and 90% were male. Both symmetric and asymmetric
      protrusions were treated. Patients whose chest was not malleable, and whose
      sternum could not be brought to a desirable position with pressure from the
      operator's hand, were treated by the open or "Ravitch" technique. After 2 or more
      years, the bar, wires stitches, screws, and fixation plates were removed.
      RESULTS: Of 40 patients treated with this procedure, 20 have undergone bar
      removal with the following results: 10 excellent, 4 good, 4 fair, and 2 poor.
      Average blood loss was 15 mL. Average length of hospital stay was as follows:
      implant, 3.8 days; removal, 1.4 days. Patients returned to routine activity 14
      days after repair. Average follow-up since primary repair is 2.49 years. In those
      who have had bar removal, it is 1.53 years. Complications were pneumothorax in 1
      patient, treated with chest tub e suction; skin adherence in 8 cases; seroma in
      6; wire breakage in 3; persistence of pain in 1; and infection in 1. Technical
      modifications (selecting younger patients, excluding patients with a stiff
      thoracic wall, submuscular insertion of the bar, stronger pericostal wire) have
      been associated with no complications in the last 16 cases. CONCLUSIONS: This
      experience with a new, minimally invasive technique for the treatment of pectus
      carinatum shows it to be safe and effective. The correction obtained was highly
      satisfactory with minimal complications. It should be considered in appropriate
      cases as an alternative to more invasive techniques.

PMID- 19159729
TI  - Spectrum of hepatic hemangiomas: management and outcome.
AB  - PURPOSE: Infants with multiple cutaneous hemangiomas often present with hepatic
      hemangiomas. They can follow a benign clinical course or require complex
      management. We reviewed our experience in the management of hepatic hemangiomas.
      METHODS: We performed a retrospective review of patients (1996-2007) with hepatic
      hemangiomas treated in our institution. RESULTS: Twenty-six patients were
      diagnosed with hepatic hemangiomas as follows: 8 focal, 12 multiple, and 6
      diffuse lesions. Nineteen (73%) patients had associated cutaneous hemangiomas.
      Sixteen patients had multiple and 3 patients had single cutaneous hemangiomas.
      All patients with multiple or diffuse liver lesions were screened for heart
      failure and hypothyroidism. Congestive heart failure developed in 4 patients, 3/4
      of these patients had diffuse lesions. Two patients required thyroid replacement
      because of elevated thyroid-stimulating hormone. Because of progression of
      disease, 9 patients required steroid treatment. Two patients were treated with
      vincristine and 3 patients received alpha-interferon because of poor response to
      steroid treatment. Two patients went on to surgical resection for failed response
      to medical management and worsening heart failure (left lobectomy, liver
      transplant). Both patients had uncomplicated postoperative courses. Five patients
      had a previously undescribed constellation of rapidly involuting cutaneous
      hemangiomas (gone by 3 months, glut-1-negative) with associated liver lesions
      also resolving at a faster pace (mean resolution of cutaneous hemangiomas, 1.9 vs
      7.9 months; P = .001; liver, 5.8 vs 25.3 months; P = .004). All patients in our
      series survived. CONCLUSION: Patients with multiple cutaneous hemangiomas should
      be screened for hepatic lesions. Patients with diffuse or multifocal liver
      hemangiomas should be screened for congestive heart failure and hypothyroidism. A
      subgroup of rapidly involuting cutaneous hemangiomas have a significantly shorter
      time for involution of hepatic lesions. The status of cutaneous lesions can be
      used as indicators for the liver hemangiomas.

PMID- 19159730
TI  - Laparoscopic pancreatectomy for persistent hyperinsulinemic hypoglycemia of
      infancy.
AB  - BACKGROUND: Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is
      considered the most common cause of persistent neonatal hypoglycemia. Management
      of PHHI involves use of medical agents and its failure is an indication of
      surgical intervention. Traditionally, an open pancreatectomy was the standard of
      care but recently laparoscopic pancreatectomy was described. We report our
      experience with laparoscopic pancreatectomy for PHHI for the period from March
      2004 to February 2008. METHODS: A retrospective chart review was conducted for
      patients managed for PHHI with laparoscopic pancreatectomy for that period.
      Demographic and clinical data were retrieved. Descriptive data were generated,
      and SPSS version 10 statistical package (SPSS, Chicago, Ill) was used. RESULTS:
      Twelve patients diagnosed with PHHI were managed with laparoscopic pancreatectomy
      for that period. Median age at procedure was 11.5 months (range, 0.5-89 months).
      Median extent of pancreatectomy was 90% (range, 85%-95%). There were 2 (16%)
      conversions to open technique. One patient (8%) required reoperation 3 months
      after the procedure. Patients were followed up for a median of 23.5 months
      (range, 3-48 months). Four (33%) were euglycemic with no medications. Three
      patients remained on octreotide postoperatively to be euglycemic, and 3 patients
      needed a combination of octreotide and diazoxide. One patient remained euglycemic
      for 10 months then started on octreotide because of recurrence of hypoglycemia.
      One patient remained hypoglycemic postoperatively and required reoperation 3
      months later to control symptoms. He became diabetic 4 months after reoperation
      on insulin. CONCLUSIONS: Our data suggest that laparoscopic pancreatectomy for
      medically unresponsive PHHI is feasible and safe. Longer follow-up is needed to
      ascertain effectiveness.

PMID- 19159731
TI  - Management of chronic pancreatitis in the pediatric patient: endoscopic
      retrograde cholangiopancreatography vs operative therapy.
AB  - PURPOSE: The management of chronic pancreatitis (CP) in children is challenging.
      We compare endoscopic retrograde cholangiopancreatography (ERCP) to operative
      therapy (OR). METHODS: The study involved review of patients younger than 18
      years with CP who underwent ERCP or OR from 1973 to 2007. Follow-up was complete
      in 95% of patients (median, 6 years; range, 1-23 years). RESULTS: We identified
      37 children with CP; 25 (68%) were managed by OR with 20 of these previously
      failing ERCP. Twelve (32%) were managed by ERCP alone. Mean follow-up was longer
      in the OR group (5.1 vs 2.1 years; P = .02). Patients with idiopathic
      pancreatitis (58% vs 13%; P = .04) and patients with a later onset of
      pancreatitis (12.0 vs 7.4 years; P = .002) were more likely to be managed with
      ERCP alone. The patients who underwent OR had a lower rate of recurrent
      pancreatitis (39% vs 75%; P < .0001), although this did not correlate to fewer
      hospitalizations or less narcotic use compared to ERCP alone. When patients who
      failed ERCP and progressed to OR were included in the ERCP alone group, ERCP was
      worse in recurrence (90% vs 39%; P < .0001) and rate of hospitalization (55% vs
      33%; P = .04) compared to OR. CONCLUSION: Patients with CP managed by OR have a
      lower rate of recurrent pancreatitis and hospitalization compared to ERCP.

PMID- 19159732
TI  - Comparison of short- and long-term functional outcome of nonoperatively managed
      renal injuries in children.
AB  - PURPOSE: The purpose of this study was to better determine the long-term
      functional outcome of nonoperatively managed renal injuries in children. METHODS:
      After Institutional Review Board approval, all children with blunt renal injuries
      were retrospectively reviewed. Renal function, after complete healing had been
      documented radiographically (3 months postinjury), was evaluated through
      measurements of blood urea nitrogen, serum creatinine, blood pressure, and split
      percentage of renal function using technetium-99m-dimercaptosuccinic acid nuclear
      scanning. Repeated data at 1 year postinjury were compared with the early follow
      up results. RESULTS: Sixteen consecutive children (mean age, 10 years; range, 3
      16 years) had complete follow-up over the study period. All children were managed
      without laparotomy. Injury grades were as follows: grades I to III, 4; grade IV,
      9; and grade V, 3. No child had an abnormal blood urea nitrogen, serum
      creatinine, or blood pressure measurement at follow-up. Consistent with previous
      results, percentage of renal function by technetium-99m-dimercaptosuccinic acid
      scanning was influenced by injury grade at the early 3-month follow-up (46.5% +/-
      4.5%, 42% +/- 7.1%, and 32.7% +/- 5.9% [mean +/- SD] for grades I-III, grade IV,
      and grade V, respectively). One-year functional results for the high-grade
      injuries also correlated to initial injury grade and were not significantly
      different from the results at early follow-up (43.8% +/- 4.8%, 41.9% +/- 6.6%,
      and 31.35 +/- 5.7% [mean +/- SD] for grades I-III, grade IV, and grade V,
      respectively; P = not significant). No child required delayed surgery.
      CONCLUSIONS: Long-term (1 year) functional outcome in nonoperatively managed
      renal injuries in children appears preserved and is influenced by injury grade.

PMID- 19159733
TI  - Equestrian injuries in children.
AB  - PURPOSE: Equestrian activities are regarded by some as high-risk sports, and our
      recent experience suggested this to be true. We undertook this study to review
      our experience with pediatric equestrian injuries. METHODS: After institutional
      review board approval, we reviewed emergency department and hospital admissions
      for children 0 to 18 years, with equestrian trauma, over an 11-year period.
      RESULTS: There were 164 encounters with 135 girls and 29 boys. Most injuries
      (82%) occurred after falling or being thrown from the animal, and only 12%
      occurred during jumping or rodeo competitions. The remaining injuries were
      secondary to being trampled, kicked, or trapped under the animal. Eighty-seven
      children required hospital admission. Lacerations and contusions (58%) or
      orthopedic injuries (31%) were most common in the emergency department cohort. In
      the admission cohort, injury sites included orthopedic (34%), head (23%), abdomen
      (21%), and chest (11%). Multiple injuries occurred in 13%. A significant number
      of children required surgical interventions, including 19 orthopedic procedures,
      4 laparotomies, 3 facial reconstructions, and 2 craniotomies. The average length
      of stay was nearly 4 days, with 60% of the children requiring intensive care
      admission. There were no deaths. One child was discharged to rehab, the rest were
      sent home. CONCLUSIONS: In our experience, more than one third of the children
      admitted after sustaining injuries in horse-related sports required surgical
      interventions. Children participating in equestrian activities are at risk for
      substantial injury, and pediatric care providers must maintain a high index of
      suspicion when evaluating these children.

PMID- 19159734
TI  - Traumatic cervical spine injuries: characteristics of missed injuries.
AB  - PURPOSE: Computed tomographic (CT) scanning has mostly replaced x-rays as an
      imaging modality, but concerns exist because of excess radiation, missed
      injuries, and whether it is the definitive procedure for intubated patients. The
      purpose of this study was to characterize missed cervical spine injuries (CSIs).
      METHODS: All pediatric (<18) trauma patients from 2004 to 2006 were analyzed.
      Age, sex, Injury Severity Score (ISS), mechanism, time, and missed injuries were
      reviewed. Flexion/extension views were used in patients with prolonged
      intubation. Descriptive statistics, chi(2), Student's t test, and bivariate
      correlation were used. RESULTS: There were 1307 pediatric trauma patients
      admitted with 318 imaged for potential CSI. Computed tomography was the sole
      imaging study in 200, x-rays in 64, and both in 54. Time to C-spine clearance was
      similar for all modalities (P > .05). For CT, 34 (10.7%) were initially positive
      for CSI with 7 false-positives (FPs) and no false-negative (FN). There were 18
      patients with CSI identified by x-ray, with 5 FPs and 5 FNs (missed injuries).
      The 5 FNs missed by x-ray were all positive by CT scan and required no
      intervention. None of the flexion/extension views revealed an additional injury.
      Sex, intubated patients, ISS, age, type, and injury location were not predictive
      of a missed injury (P > .05).The sensitivity of CT scan was 1.0, specificity was
      0.976, and the positive predictive value was 79.4%. The sensitivity of plain x
      ray was 61.5%, the specificity was 1.6%, and the positive predictive value was
      61.5%. CONCLUSIONS: Our data suggest that CT scans should be the primary modality
      to image a CSI. Flexion/extension views did not add to the decision making for C
      spine clearance after CT evaluation.

PMID- 19159735
TI  - Surgical quality improvement: a simplified method to apply national standards to
      pediatric trauma care.
AB  - BACKGROUND: The emerging "pay for performance" national initiative mandates the
      development of valid metrics for risk stratification and performance assessment.
      The International Classification Injury Severity Score (ICISS) predicts survival
      from injury and is calculated as the product of survival risk ratios (SRRs) for a
      patient's 3 worst injuries. Survival risk ratios are derived as the proportion of
      fatalities for every International Classification of Diseases, Ninth Edition,
      Clinical Modification, diagnosis in a "benchmark" population. We hypothesized
      that the ICISS prediction model derived from the National Pediatric Trauma
      Registry (NPTR) would accurately predict mortality in an independent sample from
      a single pediatric trauma center (PTC) and could be applied to the NSQIP
      methodology to analyze performance. METHODS: The ICISS survival probabilities
      (Ps) were calculated for PTC patients using SRRs computed from 102,608 NPTR
      records. Records with a single diagnosis and Ps of 1 were excluded from the
      analysis. Receiver operator characteristics analysis (ROC) was used to evaluate
      the accuracy of Ps to predict mortality. The Hosmer-Lemeshow statistic was used
      to determine the degree that the NPTR-derived expected probabilities matched the
      observed mortality profile at the PTC. Program performance from 2000 to 2004 was
      then evaluated using Ps adjusted by logit transformation to predict expected
      mortality (E) for each year cohort. Observed mortality divided by expected
      mortality (O/E) was calculated for each year group to compare PTC performance to
      the NSQIP standard of one. The influence of injury severity on these results was
      determined by evaluating the correlation between O/E and mean Ps of each year
      cohort. RESULTS: A total of 1523 records were analyzed. The ROC area under the
      curve (AUC ) for Ps was .947 (confidence interval, .934-.957). The Hosmer
      Lemeshow statistic (chi(2) = 5.102; df = 8; P = .747, not significant) indicated
      the model fit the data well. Adjusted O/E ratio after logit transformation of Ps
      for the PTC demonstrated initial performance slightly below standard (1.000778)
      followed by performance better than expected for the subsequent 4 years (range,
      .6466-.9784). The ratio of observed (O) to expected (E) demonstrated no
      correlation to mean Ps (r(2) = .378; P = .208). CONCLUSION: These data validate
      the application of injury diagnosis derived survival probabilities as objective
      metrics for determining performance using the NSQIP methodology. Incorporation of
      these objective predictors of expected outcome to calculation of the risk
      adjusted O/E ratio enables trend analysis of program performance over time. The
      lack of significant correlation between O/E and mean Ps demonstrates that NSQIP
      does indeed reflect process of care while adjusting for severity of patient
      pathologic condition.

PMID- 19159736
TI  - Establishing a regional pediatric surgical service in the setting of universal
      health care: a glimpse into the future.
AB  - PURPOSE: Increasing health care expense and rising numbers of uninsured Americans
      have led many to propose a national health insurance. This study describes the
      process, rationale, and requirements in creating a regional pediatric surgical
      service in the setting of a single-payer system. METHODS: Our health care system
      consists of 10 medical centers providing comprehensive care to more than 3
      million members. All services are provided by salaried physicians/practitioners
      to prepaid members. Before July 2004, pediatric surgical care was performed at
      multiple medical centers with many services contracted out. Starting July 2004, a
      multidisciplinary, comprehensive pediatric perioperative plan was established.
      Implementation has occurred in steps; current status and preliminary results are
      reviewed. RESULTS: Strict guidelines for pediatric anesthesia and requirements
      for support services, personnel, and equipment were defined. Pediatric surgery is
      now performed at 3 community medical centers and 1 tertiary, teaching hospital.
      Operative cases were assigned to each center based on age, complexity, level of
      postoperative care, and location. A single high-volume, center for complex care
      has been established. Access to care was excellent; more than 90% of outpatient
      consultations were seen within 2 weeks. Utilization of services was 94% in 2006
      and 98% in 2007. Physician and patient satisfaction were high. Additional
      pediatric surgeons have been hired and nearly all care has been internalized.
      Given the proximity to a major children's hospital, specialty services have not
      been duplicated. CONCLUSION: Establishing a multidisciplinary, comprehensive
      pediatric perioperative plan provided standards for supporting pediatric surgical
      services at community hospitals. This regional service may be a model for the
      future of specialty care, especially in the setting of a single-payer system.

PMID- 19159737
TI  - Training general surgery residents in pediatric surgery: educational value vs
      time and cost.
AB  - BACKGROUND: This study evaluated the educational value of pediatric surgery
      rotations, the likelihood of performing pediatric operations upon completing
      general surgery (GS) residency, and time and cost of training GS residents in
      pediatric surgery. METHODS: A survey was administered to GS residents that
      evaluated the pediatric surgery rotation and anticipated practice intentions. A
      retrospective analysis (2005-2006) of operative times for unilateral inguinal
      hernia repair, bilateral inguinal hernia repair, and umbilical hernia repair was
      also performed. Procedure times were compared for operations performed by a
      pediatric surgeon with and without GS residents. Cost analysis was based on time
      differences. RESULTS: General surgery residents (n = 19) considered the pediatric
      surgery rotation to have high educational value (4.7 +/- 0.6 of 5) with extensive
      teaching (4.6 +/- 0.7) and operative experience (4.4 +/- 0.8). Residents listed
      pediatric surgery exposure, operative technique, and observed work ethic as most
      valuable. Upon graduation, residents expect to perform pediatric operations 2 to
      3 times annually. Thirty-seven percent of residents felt competent to perform
      appendectomy (patients >5 years), 32% appendectomy (3-5 years), 21% gastrostomy
      (>1 year), and 11% inguinal herniorrhaphy (>1 year). Operative times and costs
      were significantly higher in operative procedures performed with a GS resident.
      CONCLUSION: General surgery residents considered pediatric surgery as a valuable
      educational experience. Residents anticipate performing pediatric operations a
      few times annually. Training GS residents in pediatric surgery increased
      operative time and cost. This information may be useful in determining the
      appropriate setting for resident education as well as budget planning for
      pediatric surgical practices.

PMID- 19159738
TI  - Surgeon-performed ultrasound for diagnosis of pyloric stenosis is accurate,
      reproducible, and clinically valuable.
AB  - PURPOSE: We will demonstrate that a surgical resident with proven accuracy in the
      diagnosis of hypertrophic pyloric stenosis (HPS) can teach other surgeons to
      diagnose HPS with reproducible accuracy. METHODS: A surgical resident with proven
      sonographic accuracy in diagnosing HPS instructed 5 other surgical residents in
      the technique. Consecutive patients referred to pediatric surgery with a presumed
      clinical diagnosis of HPS were examined, and measurements of residents were
      compared with formal radiology studies. Each surgeon was proctored for 5
      examinations before independent evaluation and was blinded to results from both
      radiologists and other residents. Results were evaluated using Student's t test;
      P less than .05 was considered significant. RESULTS: Seventy-one patients were
      evaluated by 5 surgical residents. Residents were diagnostically accurate in all
      cases. There was no statistically significant difference between pyloric muscle
      thickness or channel length measurements obtained by radiology and any of the
      residents. CONCLUSION: Surgeon-performed ultrasound examination for the diagnosis
      of HPS is accurate and reproducible through surgeon-to-surgeon instruction on
      appropriate technique. This skill is a valuable asset in the initial surgical
      evaluation of any patient with suspected HPS, expediting appropriate management.

PMID- 19159739
TI  - Preoperative prediction of need for fundoplication before gastrostomy tube
      placement in children.
AB  - PURPOSE: Percutaneous endoscopic gastrostomy (PEG) tube placement is a common
      procedure performed for children with oral aspiration and failure to thrive. The
      concurrent presence of gastroesophageal reflux (GER) may be difficult to diagnose
      in these children and may dictate the need for an antireflux procedure. The
      purpose of this study was to review our preoperative evaluation of children
      undergoing PEG placement to better elucidate preoperative factors that may
      require eventual fundoplication. METHODS: A retrospective review at a tertiary
      care, children's hospital between May 2002 and August 2007 was performed of
      patients undergoing PEG placement. Patients were identified through database
      search by operative procedure codes. Patient groups were defined as those
      undergoing PEG alone (group 1) and those requiring fundoplication after prior PEG
      (group 2). Comparison of patient demographics and radiologic qualitative results
      of GER was analyzed using chi(2) analysis, with significance determined at P <
      .05. RESULTS: A total of 863 patients underwent PEG placement over this 64-month
      period. A sampled cohort of patients undergoing PEG over a year comprised group
      1. Forty-four patients (5.1%) underwent Nissen fundoplication after prior PEG
      placement (group 2). Patient demographics were similar between the groups.
      Comparison of comorbid conditions and qualitative indicators of GER between the
      groups showed only cerebral palsy had a significantly higher associated risk of
      GER that required antireflux surgery. Preoperative clinical assessment had a 95%
      positive predictive value in identifying children who required only PEG.
      CONCLUSIONS: Despite the high predictive value of individualized clinical
      assessment in the ultimate decision for gastrostomy without need of
      fundoplication, further studies are needed to determine whether children with
      conditions such as cerebral palsy may require a concurrent antireflux surgery at
      the time of gastrostomy.

PMID- 19159740
TI  - The use of intraabdominal tissue expanders as a primary strategy for closure of
      giant omphaloceles.
AB  - BACKGROUND: Giant omphaloceles present a unique challenge to pediatric surgeons
      because of the difficulty in obtaining timely, tension-free closure of tissues
      over the defect. Reports of the use of tissue expanders in the subcutaneous
      space, intramuscular space, or intraabdominal cavity have illustrated the
      usefulness of this technique to provide biologic closure of abdominal wall
      defects. However, these reports have focused on use of tissue expanders as a
      second-line treatment after other options, such as silastic silos or attempted
      primary closure, have failed. METHODS: We report 2 cases in which intraabdominal
      tissue expanders were used as a primary strategy to obtain closure of giant
      omphalocele defects. CASE REPORTS: The first patient was a baby boy born at 36
      weeks by date who was prenatally diagnosed with a giant omphalocele. An
      intraabdominal tissue expander was placed at 2 weeks of age. The tissue expander
      was removed and his abdomen was primarily closed at 8 weeks of age. The second
      patient was born at 25 weeks gestation as part of a twin gestation with severe
      intrauterine growth retardation (600 g birth weight). Bedside reduction was not
      attempted because of severe pulmonary hypertension and significant loss of
      abdominal domain because of herniated liver and bowel. At 8 months of age, she
      underwent laparoscopically assisted placement of an intraabdominal tissue
      expander. At 9 months of age, the tissue expander was removed, all abdominal
      viscera were reduced, and the defect was closed using only an 8 x 8-cm piece of
      AlloDerm (LifeCell, Branchburg, NJ). Both children are currently at home and
      doing well. CONCLUSIONS: We believe that early use of intraabdominal tissue
      expanders provides a more expedient method of obtaining closure of the defect in
      giant omphaloceles.

PMID- 19159741
TI  - The association of cyclic parenteral nutrition and decreased incidence of
      cholestatic liver disease in patients with gastroschisis.
AB  - PURPOSE: The aim of the study was to investigate the effect of prophylactic
      cycling of parenteral nutrition (PN) on PN-induced cholestasis in patients with
      gastroschisis. METHODS: Retrospective review of initial hospital admission charts
      for each patient with gastroschisis from 1996 to 2007 was performed. RESULTS: One
      hundred seven patients were analyzed (36 prophylactically cycled, 71 control).
      Prophylactic cycling of PN was initiated at a mean age of 23 days (range, 7-89
      days). Patients were followed for a total of 4255 days with 27 developing
      hyperbilirubinemia (cycled, 5; continuous, 22). Time to hyperbilirubinemia was
      longer in the prophylactically cycled group (P = .005). Cumulative incidence of
      hyperbilirubinemia at 25 and 50 days of PN exposure was 5.7% and 9.8% (cycled) vs
      22.3% and 48.8% (continuous). At any given time, children in the continuous group
      were 4.76 times more likely to develop hyperbilirubinemia (95% confidence
      interval, 1.62-14.00). After adjusting for confounding factors, children in the
      continuous group were 2.86 times more likely to develop hyperbilirubinemia (95%
      confidence interval, 0.86-9.53), but the difference was not significant (P =
      .088). CONCLUSIONS: Prophylactic cyclic PN is associated with a decreased
      incidence and prolonged time to onset of hyperbilirubinemia. Other factors,
      however, significantly affect this relationship. Prospective randomized
      investigation is warranted to investigate for a possible causal relationship.

PMID- 19159742
TI  - Conservative surgery plus brachytherapy treatment for boys with prostate and/or
      bladder neck rhabdomyosarcoma: a single team experience.
AB  - PURPOSE: The aim of this study is to report the results of a conservative surgery
      + brachytherapy treatment for boys with prostate and/or bladder-neck
      rhabdomyosarcoma avoiding total cystectomy or prostatectomy and external
      radiotherapy. PATIENTS: From 1991 to 2007, 26 boys were operated for a residual
      mass after chemotherapy (1 for local relapse). All patients underwent a
      conservative surgical procedure, with bladder-neck and urethra preservation.
      Surgery was never microscopically complete. Brachytherapy was systematically
      performed after tumor resection, as a perioperative procedure, consisting of 2
      loops encompassing the prostate and the bladder-neck area. A dose of 60 Gy was
      delivered with low dose rate. Bladder function was evaluated clinically and with
      urodynamic study for boys with abnormal continence. RESULTS: Median age at
      operation was 23 months (9 months-11 years). Seventeen boys underwent a partial
      prostatectomy associated in 5 with a partial cystectomy. The remaining 9 patients
      underwent a partial cystectomy with no procedure at the level of the prostate. At
      a median follow-up of 4 years (10 months-14.5 years), 24 of 26 boys are alive.
      Only 1 patient relapsed locally out of the brachytherapy field and died. A second
      boy died from metastatic relapse. Only 1 patient with bladder dysfunction after
      treatment underwent a total cystectomy. Four patients are too young to be
      evaluated for bladder function (<4 years of age). Seven patients, aged 4 to 6
      years, have daytime continence, 1 has diurnal dribbling. Among 11 boys older than
      6 years, 9 (82%) are normally continent (3 after temporary dribbling), 2 have
      diurnal dribbling treated by bladder education. CONCLUSION: Even if very long
      term sequelae of brachytherapy cannot be evaluated, this conservative combined
      treatment may allow normal continence in nearly all patients, even after
      temporary diurnal incontinence and should be discussed as an alternative to
      external radiotherapy or radical surgery.

PMID- 19159743
TI  - Malignant pancreatic tumors: incidence and outcome in 58 pediatric patients.
AB  - OBJECTIVE: The purpose of the study was to examine current incidence trends and
      outcomes for children with pancreatic malignancies. METHODS: The Surveillance,
      Epidemiology, and End Results registry (1973-2004) was examined for pediatric
      patients with pancreatic malignancies (up to 19 years of age). RESULTS: Malignant
      pancreatic neoplasms were identified in 58 patients. Females outnumbered males
      1.9 to 1 (38 vs 20) for an age population-adjusted incidence of 0.021 and 0.015
      per 100,000. Overall, 70% (n = 41) of patients were white. Asians had the highest
      incidence. Tumors were classified as exocrine (n = 31, 53.4%), endocrine (n = 19,
      32.8%), or sarcomas (n = 5, 8.6%). Exocrine tumors included pancreatoblastoma (n
      = 10), solid-cystic tumor (SCT) (n = 10), ductal adenocarcinoma (DA) (n = 7), and
      acinar cell carcinoma (ACC) (n = 4). All SCTs and 80% of pancreatoblastomas were
      seen in females, whereas males had a higher incidence of DA 71% (P = .036).
      Ductal adenocarcinoma, SCT, acinar cell carcinoma, sarcomas, and endocrine tumors
      were more common in children older than 10 years, whereas pancreatoblastoma was
      more common in younger children (P = .045). Almost half of patients (n = 25)
      presented with distant metastasis; of these, 44% were endocrine tumors. Survival
      was significantly greater for female patients (P = .004) and for those who had
      surgery (P = .001) by both univariate and multivariate analysis. There was a
      significant difference in tumor type 15-year survival with DA having the worst
      (23%) and SCT the best (100%). CONCLUSIONS: Pediatric pancreatic neoplasms are
      uncommon and carry a variable prognosis. Both female sex and surgery were
      independent predictors of improved survival.

PMID- 19159744
TI  - Neural progenitor cell-mediated delivery of osteoprotegerin limits disease
      progression in a preclinical model of neuroblastoma bone metastasis.
AB  - PURPOSE: Osteoprotegerin (OPG) inhibits osteoclast activation and reduces
      osteolysis in bone tumors. We hypothesized that tumor-tropic neural progenitor
      cells (NPCs) engineered to express OPG would reduce neuroblastoma disease burden
      in the bone. METHODS: Stable expression of green fluorescent protein (NPC-GFP)
      and OPG (NPC-OPG) was established in human NPCs by lentivirus-mediated
      transduction. Bone disease was established by intrafemoral injection of
      luciferase-expressing human neuroblastoma (CHLA-255) cells into 20 SCID mice.
      Three weeks later, mice began receiving intravenous injection of 2 x 10(6) NPC
      OPG or NPC-GFP (control) every 10 days x 3 doses. Disease was monitored with
      quantitative bioluminescence imaging and x-ray images, which were evaluated on a
      scale of 0 to 4. These studies were approved by the Institutional Animal Care and
      Use Committee. RESULTS: Osteoprotegerin treatment in vitro produced no direct
      toxicity to tumor cells. Coculture of tumor cells with bone marrow significantly
      increased activation of bone marrow-derived osteoclasts as assessed by tartrate
      resistant acid phosphatase staining (156 +/- 10.8 osteoclasts per well) compared
      to bone marrow culture alone (91.67 +/- 4.7, P = .005). This increase was
      abrogated by adding OPG-containing media (68.3 +/- 2.8, P = .001). NPC-OPG slowed
      tumor progression (108-fold increase from pretreatment) compared to mice treated
      with NPC-GFP (538-fold), as judged by bioluminescence imaging. X-rays
      subjectively demonstrated less bone disease in NPC-OPG-treated mice (2.27 +/-
      0.25) compared to NPC-GFP-treated mice (3.25 +/- 0.22, P = .04). CONCLUSIONS:
      Neural progenitor cell-mediated delivery of OPG slowed disease progression in a
      preclinical model of neuroblastoma bone metastasis. The decrease in bone disease
      was not from direct tumor cell toxicity but likely occurred indirectly through
      inhibition of osteoclast-directed bone resorption. Thus, targeted delivery of OPG
      by NPCs may be effective in the treatment of neuroblastoma bone metastasis.

PMID- 19159745
TI  - Ketone bodies inhibit the viability of human neuroblastoma cells.
AB  - PURPOSE: Recent studies have shown that brain tumor cells, unlike normal brain
      cells, are largely dependent upon glucose for energy and are not able to use
      ketone bodies as a primary energy source. These findings are thought to be
      because of decreased expression of succinyl-coenzyme A:3-oxoacid coenzyme A
      transferase (SCOT), a key enzyme involved in ketone body metabolism. Because of
      their neural crest origin, we hypothesized that neuroblastoma cells would also be
      unable to use ketone bodies as a primary energy source. METHODS: Human foreskin
      fibroblasts (control) and human neuroblastoma cells (SK-N-AS) were grown in
      standard media with glucose (glc+), standard media without glucose (glc-),
      glucose-free media with acetoacetate, or glucose-free media with beta
      hydroxybutyrate. Cell viability was determined with MTT [3-(4,5-dimethylthiazol-2
      yl)-2,5 diphenyltetrazolium bromide] assay and apoptosis with fluorescence
      activated cell sorting analysis. Immunoblotting was performed to SCOT protein.
      RESULTS: Neuroblastoma cell viability was significantly decreased in the
      acetoacetate and hydroxybutyrate media by 52% and 61%, respectively, compared
      with control media. In addition, neuroblastoma cells showed significantly more
      apoptosis in the ketone media. Viability and apoptosis in the normal fibroblasts
      were not affected by the culture media. The expression of SCOT protein was
      significantly less in human neuroblastoma cells compared with the control
      fibroblasts. CONCLUSIONS: Unlike human fibroblasts, neuroblastoma cells were
      unable to use ketone bodies as an energy source, likely because of their
      decreased expression of SCOT protein. Dietary manipulation using ketone bodies in
      accordance with SCOT expression may be a novel therapeutic strategy for
      neuroblastoma.

PMID- 19159746
TI  - Decreased mortality but increased morbidity in neonates with jejunoileal atresia;
      a study of 114 cases over a 34-year period.
AB  - PURPOSE: The aim of the study was to evaluate patient demographics,
      classification and location of the atresia, operative management, postoperative
      care, and outcome in 114 infants with jejunoileal atresia (JIA) over a period of
      more than 3 decades. METHODS: This was a retrospective case series in a tertiary
      care teaching hospital. Records of all patients with JIA treated at the authors'
      institution between 1971 and 2004 were examined. RESULTS: Sixty-two percent of
      atresia and stenosis was noted in the jejunum, 30% in the ileum, and 8% in both
      the jejunum and the ileum. Atresias and stenosis were classified as follows: 7%
      type 0, 16% type I, 21% type II, 24% type IIIa, 10% type IIIb, 22% type IV.
      Gastrointestinal anomalies were encountered in 24% of patients, genitourinary
      malformations in 9%, cystic fibrosis in 9%, neurologic anomalies in 6%, and
      congenital heart disease in 4%. Operative management included resection with
      primary anastomosis in 69% of all patients and temporary enterostomies in 26%.
      After operative management, 15% of children had resultant short bowel syndrome.
      Oral feeding was allowed on median day 7, and full energy expenditure via the
      enteric route was reached on median day 20. Forty-seven percent of infants
      required central venous line placement for total parenteral nutrition. Early
      postoperative complications occurred in 28% of patients with JIA and late
      postoperative complications in 17%. We observed a mortality rate of 11%.
      CONCLUSIONS: This is one of the largest series of neonates with JIA described.
      Short bowel syndrome seems to be the biggest problem resulting in longer hospital
      stay, more feeding problems, and higher morbidity and mortality rates. Management
      of children with short bowel syndrome has improved because of the use of total
      parenteral nutrition, new operative techniques, and better intensive care. In the
      last 15 years, survival has increased at the cost of the surviving children as we
      noted a higher percentage of late complications.

PMID- 19159747
TI  - Magnamosis: magnetic compression anastomosis with comparison to suture and staple
      techniques.
AB  - PURPOSE: An ideal anastomosis between hollow viscera should be easily performed,
      strong, and operator independent. We hypothesized that transluminal attraction
      between magnets in the intestine could be harnessed to create an intestinal
      compression anastomosis (magnamosis) with these characteristics. We further
      hypothesized that variation of attraction force and geometry of compression would
      affect the quality of the intestinal anastomosis. METHODS: We designed a self
      orienting device composed of 2 neodymium-iron-boron magnets affixed to
      polytetrafluoroethylene moldings. Two topologies were evaluated: one designed
      with 'uniform' compression and the other with 'gradient' compression. Sixteen
      young adult pigs (Sus scrofa) underwent laparotomy with creation of a magnetic
      side-to-side anastomosis: 8 with the uniform device and 8 with the gradient
      device. Each also had a stapled anastomosis, and 5 had an additional hand-sutured
      anastomosis. Animals were euthanized at 1, 2, and 3 weeks after operation, then
      anastomoses were compared on the basis of gross appearance, histology, functional
      radiography, and mechanical integrity. RESULTS: All magnetic devices formed
      patent anastomoses without leak. One stapled anastomosis resulted in a contained
      leak. Mechanical integrity of magnetic anastomoses was not statistically
      significantly different from staple or suture counterparts, and there was a trend
      toward greater strength with magnetic anastomoses. Comparison between device
      types revealed the gradient device trended toward greater strength and earlier
      patency (67% vs 33% at 1 week). There was no evidence of stenosis, and histologic
      examination demonstrated tissue remodeling with mucosal and serosal apposition
      across the magnamoses. CONCLUSIONS: The magnetic compression anastomosis
      (magnamosis) device is a safe and effective means of sutureless full-thickness
      intestinal anastomosis with serosal apposition in a pig model. Gradient
      compression is superior to uniform compression. This technique is compatible with
      endoscopic and natural orifice approaches.

PMID- 19159748
TI  - Preservation of intestinal motility after the serial transverse enteroplasty
      procedure in a large animal model of short bowel syndrome.
AB  - INTRODUCTION: Serial transverse enteroplasty (STEP) has been shown to improve
      bowel function in short bowel syndrome. The effect of the STEP procedure on
      intestinal motility is not known, but some have hypothesized that it could
      disrupt bowel innervation and thus impair intestinal motility. METHODS: Growing
      Yorkshire pigs (n = 7) underwent 3 operations at 6-week intervals: (1) reversal
      of 50 cm of jejunum, (2) 90% bowel resection +/- STEP to the proximal dilated
      bowel (4 STEP, 3 control), and (3) implantation of serosal strain gauges. At each
      operation, baseline and post-octreotide small intestinal motility was studied
      with continuously perfused manometry catheters using non-anticholinergic
      anesthesia. In addition, awake monitoring was performed using strain gauge
      analysis 1 week after the third operation. Characteristics of phase III of the
      migrating motor complex (MMC) were compared between and within groups using t
      test, chi(2), and analysis of variance, with significance set at P < .05.
      RESULTS: Manometry data from the third surgery revealed no differences between
      groups or compared with baseline within groups for the presence and
      characteristics of phase III of the MMC. Specifically, the mean amplitude and
      frequency of phase III after octreotide, and both the mean baseline and mean
      octreotide-stimulated motility indices were equivalent. The duration of phase III
      after octreotide stimulation was significantly increased in the STEP animals,
      suggesting a potential benefit of the STEP procedure. Strain gauge analysis,
      performed in awake animals, confirmed no differences between the groups for basal
      and octreotide-stimulated characteristics of phase III of the MMC. CONCLUSIONS:
      These preliminary data suggest that the STEP procedure in a porcine model of
      short bowel syndrome does not interfere with baseline or hormonally stimulated
      motility within the small bowel. These findings further support the STEP
      procedure as a safe option for the surgical management of short bowel syndrome.

PMID- 19159749
TI  - Novel intravenous (13)C-methionine breath test as a measure of liver function in
      children with short bowel syndrome.
AB  - Monitoring hepatic function in children with short bowel syndrome (SBS) and
      parenteral nutrition-associated liver disease (PNALD) is currently limited to
      conventional blood testing or liver biopsy. Metabolism of the stable isotope L[1
      (13)C]methionine occurs exclusively in liver mitochondria and can be
      noninvasively quantified in expired breath samples. We hypothesized that the
      (13)C-methionine breath test ((13)C-MBT) could be a safe, noninvasive, and valid
      measure of hepatic mitochondrial function in children with SBS and PNALD.
      METHODS: Baseline breath samples were collected in 8 children with SBS before
      intravenous administration of 2 mg/kg of L[1-(13)C]methionine. Six paired breath
      samples were obtained at 20-minute intervals. The (13)CO(2) enrichment was
      analyzed using isotope ratio mass spectrometry. RESULTS: All 8 patients (5 males;
      mean age, 8.9 months) tolerated the (13)C-MBT without adverse events. Two
      patients underwent serial testing. One patient, tested before and after
      resolution of cholestasis, demonstrated increased cumulative percentage dose
      (4.7% to 6.6%) and area under the curve (AUC) (270-303). A second patient with
      progressive PNALD demonstrated decreased cumulative percentage dose (from 7.8% to
      5.9%) and AUC (from 335 to 288). CONCLUSION: The (13)C-MBT is a feasible, safe,
      and potentially clinically relevant measure of hepatic mitochondrial function in
      children with SBS and PNALD.

PMID- 19159750
TI  - The impact of hospital type and experience on the operative utilization in
      pediatric intussusception: a nationwide study.
AB  - PURPOSE: To determine the impact in clinical outcomes of pediatric idiopathic
      intussusceptions from hospital experience and designation as children's hospitals
      (CH) and non-children's hospitals (NCH) in the US. METHODS: A retrospective study
      was performed on 1263 children with idiopathic intussusception, 2 months to 3
      years of age in 2000 and 2003 by extracting data from the Healthcare Cost and
      Utilization Project Kid's Inpatient Database. Main outcome measures were
      utilizations of operation and radiologic reduction. Statistical significance was
      defined as P < .05. RESULTS: The median hospital volume of intussusceptions was
      higher at CH (2.5 vs 0.5 cases per year, P < .001) compared to NCH. Children
      treated at CH had lower risk of operation (55 vs 68%, P < .001) and higher
      likelihood of radiologic reduction (39 vs 26%, P < .001) compared to NCH.
      Multivariate regression analysis showed a 17% reduction of operative utilization
      at CH vs NCH. Outcomes were positively related to experience as high-volume
      hospitals reduced operative utilization by 19%. Rates of successful radiologic
      reduction were similar between hospital types, which was 85% nationally.
      CONCLUSION: Children with intussusception have decreased likelihood of operation
      when treated at CH compared to NCH. This decreased operative utilization can be
      attributed to the increased experience and utilization of radiologic reduction at
      these specialty hospitals.

PMID- 19159751
TI  - Contrast enema for pediatric intussusception: is reflux into the terminal ileum
      necessary for complete reduction?
AB  - PURPOSE: Complete contrast enema reduction of intussusception is traditionally
      considered confirmed when contrast is seen refluxing into the terminal ileum.
      Operative intervention is typically indicated when the intussusception is not
      completely reduced. This study reviews the outcomes after symptomatic reduction
      of intussusception without requiring reflux of contrast into the terminal ileum.
      METHODS: A retrospective review of all pediatric patients treated for
      intussusception between 1996 and 2006 was performed. Diagnostic modality,
      operative reports, and hospital records were reviewed. RESULTS: One hundred sixty
      eight patients were treated for intussusception during the study period. Median
      age was 9.9 months (59 days to 16.7 years). One hundred thirty-seven (81.5%)
      patients underwent contrast enema as the initial diagnostic/therapeutic modality.
      On contrast enema, 15 (10.9%) patients demonstrated reduction of the
      intussusception but without contrast refluxing into the terminal ileum. All 15
      patients had improvement of symptoms. Six (40%) patients underwent operative
      intervention and were found to have a completely reduced intussusception. Two
      (13.3%) patients had repeat contrast enema the next day confirming complete
      reduction. The remaining 7 (46.7%) patients were observed without further
      radiographic studies, and all 7 patients were discharged the following day
      tolerating full feedings. There were no recurrent intussusceptions. CONCLUSION:
      Nonoperative management may be used in patients with reduced intussusception
      despite lack of contrast refluxing into the terminal ileum if symptoms resolve.

PMID- 19159752
TI  - Development of a standardized definition for Hirschsprung's-associated
      enterocolitis: a Delphi analysis.
AB  - PURPOSE: The reported incidence of Hirschsprung's-associated enterocolitis (HAEC)
      is extremely variable. A standardized definition would permit comparison of
      different studies and provide an interpretable outcome measure for future
      prospective studies in patients with Hirschsprung's disease. METHODS: The Delphi
      method is a technique for achieving consensus among a panel of experts. A list of
      38 potential criteria from the history, physical examination, radiologic studies,
      and pathologic specimens was made available to pediatric surgeons and
      gastroenterologists who have contributed to the literature on Hirschsprung's
      disease. Each expert ranked the diagnostic importance of each item using a Likert
      scale. In subsequent surveys, the same process was used, but the means and SDs
      from previous rounds were included as a way of influencing the experts toward
      consensus. Cronbach's alpha was used after each round to measure variability
      among the experts. Once consensus was reached, an overall "HAEC score" was
      developed by assigning a value of 1 or 2 to each item that was considered
      important by the expert panel. The score was then validated by circulating 10
      clinical cases to the panel and asking if each represented HAEC or not. RESULTS:
      Twenty-seven experts completed the survey. Cronbach's alpha increased from 0.93
      after the first round to 0.97 after the second. Criteria receiving the highest
      scores were diarrhea, explosive stools, abdominal distension, and radiologic
      evidence of bowel obstruction or mucosal edema. Eighteen items were included in
      the score. During the validation process, the score agreed with the experts in 9
      of the 10 case scenarios. CONCLUSION: The most important clinical diagnostic
      criteria for HAEC were identified from a larger pool of potential diagnostic
      items through a consensus approach using the Delphi method. A score was developed
      and validated and can now be used as a standardized and reproducible outcome
      measure for future studies in children with Hirschsprung's disease.

PMID- 19159753
TI  - Comprehensive review of procedures for total colonic aganglionosis.
AB  - PURPOSE: A variety of procedures have been described for the treatment of total
      colonic aganglionosis (TCA); however, there is no consensus as to a superior
      operative method. The objective of this review is to evaluate the operative
      methods used to treat TCA and their effectiveness with respect to morbidity,
      mortality, rates of enterocolitis, and functional outcomes. METHODS: We searched
      Medline (1950-2007) and the Cochrane Library for studies reporting the operative
      treatment of TCA. Search terms used were "aganglionosis," "Hirschsprung's
      disease," "total colonic," and "long-segment." Studies evaluated were limited to
      those that solely discussed the operative outcomes for the treatment of TCA. A
      meta-analysis was then performed for morbidity outcomes in those studies
      describing a single operative procedure. RESULTS: The search yielded 271 articles
      related to TCA. One hundred twenty-two articles discussed operative treatment of
      Hirschsprung's disease, and only 26 of these articles discussed operative
      management of TCA. Nineteen articles were isolated for statistical analysis on
      the basis of results for perioperative outcomes for a single procedure. These
      procedures included Martin (4), colonic patch modifications (4), Duhamel (2),
      endorectal pull-through (1), Kimura (2), Boley (2), Rehbein (2), Soave (1), and J
      pouch ileoanal anastomosis (1). Overall mortality was 1.9%. Meta-analysis
      revealed morbidity rates ranging from 10% to 64% depending on procedure category
      without significant outliers. Higher morbidity rates were found for the Martin
      type procedure using the descending colon but with noted higher within-group
      variance due to small sample sizes. Enterocolitis was noted in 7 studies with a
      mean of 22%. CONCLUSIONS: There is no superior operative method for the treatment
      of TCA with respect to perioperative morbidity, mortality, enterocolitis, and
      functional outcomes. The operative technique performed should be selected on
      center and surgeon familiarity and expertise.

PMID- 19159754
TI  - Rectal mucosal dissection during transanal pull-through for Hirschsprung disease:
      the anorectal or the dentate line?
AB  - PURPOSE: Both the dentate line (DL) and anorectal line (ARL) are anatomic
      landmarks for rectal mucosal dissection during transanal pull-through for
      Hirschsprung disease. We compared outcome after rectal mucosal dissection
      commencing above the DL (DL group; n = 8) with outcome after rectal mucosal
      dissection commencing on the ARL (ARL group; n = 6) with normal babies (Cont
      group; n = 10). METHODS: Rectal mucosal dissection commenced on the ARL in the
      ARL group and at various levels (0-10 mm) above the DL in the DL group. Outcome
      was assessed prospectively for 6 months using a standard structured
      questionnaire. RESULTS: Subject demographics were not significantly different.
      Differences in frequency of motions between the ARL and Cont groups were not
      statistically significant after 3 months of age, but the DL group had
      significantly more motions than the other 2 groups after 4 months of age (P <
      .01). At 6 months of age, fecal staining was 17% in the ARL group, 63% in the DL
      group, and 0% in the Cont group. Anal shape was normal in the ARL and Cont
      groups, but 50% of the DL group had visible anal mucosa. CONCLUSION: Bowel
      function in the ARL group is similar to normal, and because the ARL is easily
      identifiable without the need for subjective interpretation, we recommend using
      the ARL as a landmark for rectal mucosal dissection during transanal pull-through
      for Hirschsprung disease.

PMID- 19159755
TI  - Hirschsprung disease and fecal incontinence: diagnostic and management
      strategies.
AB  - PURPOSE: Ideally, fecal incontinence after operative management for Hirschsprung
      disease should not occur. If it does, it presents a formidable challenge. The
      purpose of this study was to describe the causes of fecal incontinence and
      present our algorithm for its treatment. METHODS: We reviewed 68 patients with
      Hirschsprung disease and fecal incontinence referred to us after surgery at other
      institutions. Patients were evaluated by contrast enema and by an examination
      under anesthesia to look specifically for the integrity of the anal canal. They
      were designated as having a dilated colon and constipation or a nondilated colon
      and a tendency to diarrhea based on their stooling pattern and the appearance of
      the contrast enema. Medical management was started that included laxatives for
      those patients with a dilated colon and constipation. For those with a nondilated
      colon and tendency to diarrhea, the management included loperamide, pectin, and a
      special dietary regimen (constipating diet, 3 meals per day, and no snacks).
      Those patients who responded to medical management were retrospectively
      considered to have been pseudoincontinent. Those who did not respond were
      considered truly incontinent. The truly incontinent group was treated with enemas
      alone for those with a dilated colon, or enemas, loperamide, pectin, and a
      constipating diet for those with a nondilated colon and tendency to diarrhea.
      RESULTS: Fifty-six patients had true incontinence and 12 had pseudoincontinence.
      Of the true incontinent group, 27 had a dilated colon and 29 had a nondilated
      colon. Five of these patients had a damaged or absent anal canal (anastomosis at
      the anal skin) and all of them had true incontinence. In the dilated colon group
      with true incontinence, 23 (85%) patients were clean after treatment. In the
      nondilated colon group with true incontinence, 23 (79%) were successfully
      treated. All patients in the pseudoincontinent groups had no soiling after
      treatment. Of 55 in the truly incontinent group, 39 (70%) had had an endorectal
      (Soave type) pull-through. CONCLUSION: Fecal incontinence after operative
      management of Hirschsprung disease represents a serious problem. Poor surgical
      technique may be a contributing factor in some of the cases. Successful
      management depends on the appropriate evaluation, which determines whether the
      incontinence is true or pseudo, and the type of colon the patient has. Each
      category can be well treated, leading most of the time to a clean child.

PMID- 19159756
TI  - Residual fistula after laparoscopically assisted anorectoplasty: is it a rare
      problem?
AB  - PURPOSE: Although various urologic complications have been reported after
      abdominoperineal pull-through and posterior sagittal anorectoplasty for the
      treatment of high-type imperforate anus, reports regarding complications after
      laparoscopically assisted anorectoplasty (LAARP) are surprisingly rare. Here, we
      discuss the potential complications of LAARP. METHODS: A retrospective study was
      conducted of 24 patients treated with LAARP from 2000 to 2006. The clinical and
      operative records were reviewed. Of the 24 patients, 18 were evaluated
      postoperatively by screening magnetic resonance imaging (MRI). RESULTS: The 24
      participants are composed of patients with rectoprostatic urethral fistula (n =
      15), rectal agenesis (n = 3), rectovesical fistula (n = 2), rectovaginal fistula
      (n = 2), and cloaca (n = 2). Defecatory function after LAARP was satisfactory.
      None of the patients had dysuria or urinary infection postoperatively. Cystic
      formations posterior to the urethra were demonstrated in 9 of the 18 cases
      examined by MRI. Postoperative voiding cystourethrography failed to demonstrate
      the lesion in 6 of 9 patients. The types of imperforate anus in this subgroup
      were rectoprostatic urethral fistula (n = 7), rectovesical fistula (n = 1), and
      rectal agenesis without fistula (n = 1). Average cyst diameter was 22 +/- 19 mm.
      Two patients with large cysts (62 and 42 mm) underwent surgical resection.
      CONCLUSIONS: Although satisfactory fecal continence could be achieved by LAARP,
      we experienced 2 cases with a large residual fistula that required surgical
      resection. In addition, screening MRI demonstrated the presence of cystic
      formations in 9 of 18 patients. We recommend that MRI be performed routinely
      during follow-up of patients treated with LAARP.

PMID- 19159757
TI  - Laser epilation is a safe and effective therapy for teenagers with pilonidal
      disease.
AB  - Pilonidal disease (PD) is a frustrating condition because of a recurrence rate as
      high as 30%. Hair insertion is the essential cause of the disease. Therefore,
      hair removal with shaving is a part of many postoperative regimens. These methods
      are resource intensive and adversely impact the life-style of both patient and
      family. Therefore, we investigated the use of laser epilation (LE) of the
      intergluteal hair in adolescents with PD as a method of permanent hair removal.
      METHODS: A retrospective review of all patients with PD who underwent LE from
      2003 to 2006 at the National Naval Medical Center, Bethesda, Md, and Walter Reed
      Army Medical Center, Washington, DC, was performed. Laser epilation of the
      intergluteal hair was carried out with a 1064 nm Nd:YAG laser (Coolglide Vantage,
      Altus/Cutera, Brisbane, Calif) at a standard fluence (joule/square centimeter),
      pulse duration, and repetition rate based on skin phototype. The patients were
      observed for hair regrowth and recurrence. RESULTS: Twenty-eight teenagers (17
      males, 11 females; mean age, 17.2 +/- 1.4 years) underwent LE. Eight patients
      presented with abscess and were managed by incision and drainage followed by
      excision and open wound management, 17 patients presented with a cyst or sinus
      and underwent excision and primary closure, and 3 patients with asymptomatic
      sinus were managed nonoperatively. Laser epilation was performed after complete
      wound healing or immediately in those patients with asymptomatic sinus disease.
      Laser epilation was well tolerated and without complication in all patients.
      Intergluteal hair was completely removed in all patients. Patients required an
      average of 5 +/- 2 LE therapy sessions for hair removal. All patients underwent
      at least 3 LE sessions (range, 3 to 7 sessions) at 4-week intervals. One female
      developed a recurrence. The mean follow-up for the group was 24.2 +/- 9.9 months.
      CONCLUSIONS: Laser epilation is a safe method to remove intergluteal hair in
      teenagers with PD. This technique is an effective adjunctive therapy for the
      treatment of PD that may reduce recurrence.

PMID- 19159758
TI  - Successful treatment of earlobe keloids in the pediatric population.
AB  - BACKGROUND: Keloid scars present a difficult treatment challenge. Recently,
      intralesional steroid injection has become a common treatment modality [Akoz et
      al. Aesthetic Plast Surg. 2002;6:184-188; Studdiford et al. JABFM. 2008;21:149
      152]. Although this has become a proven treatment technique, there is no standard
      injection protocol to which treating physicians commonly adhere. We hypothesize
      that timing of steroid injection may improve outcomes using this treatment
      technique in combination with lesion excision. METHODS: Fifteen patients with 16
      earlobe keloids were treated using a standard steroid injection protocol with
      Kenalog (Bristol-Myers Squibb, New York, NY), in combination with lesion
      excision. Strict follow-up was enforced, with repeat injections as needed at any
      sign of abnormal scar formation postoperatively. RESULTS: Of 16 lesions, 15 (94%)
      were treated successfully with no sign of lesion recurrence at 6 months of follow
      up. A single lesion was lost to follow-up and presented 18 months postoperatively
      with recurrence. This lesion was subsequently retreated successfully.
      CONCLUSIONS: Kenalog injection in combination with excision is a well-tolerated
      and effective treatment of earlobe keloids in the pediatric population. We feel
      that timing of injection and adherence to a strict follow-up regimen is crucial
      to success.

PMID- 19159759
TI  - Position paper on video-assisted thoracoscopic surgery as treatment of pediatric
      empyema.
AB  - Pediatric empyema can be managed with a variety of modalities, and the evidence
      for an ideal management strategy is limited. Early or simple effusions can be
      treated with antibiotics alone or with drainage when respiratory distress occurs.
      Once fibrinopurulent empyema has developed, therapy may involve either chest tube
      placement with instillation of fibrinolytics or video-assisted thoracoscopic
      surgery with pleural decortication. In late or fibrotic empyema, an assumption
      persists that the fibrotic peel must be managed by decortication that can be done
      either thoracoscopically or through a minithoracotomy incision. This position
      paper is coauthored by the New Technology Committee of the American Pediatric
      Surgery Association. The goal is to discuss the ongoing controversies and
      summarize, in an evidence-based manner, the various treatment options and to
      suggest a reasonable therapeutic algorithm for the care of children with empyema.

PMID- 19159760
TI  - Endovascular stenting of a penetrating axillary artery injury in a 14-year-old
      with 1-year follow-up.
AB  - In the management of pediatric trauma, certain principles that are practiced in
      children who have sustained injuries more commonly seen in adults are
      extrapolated from the adult trauma literature. The increased use of computer
      tomography angiograms in the diagnosis of penetrating vascular trauma and
      endovascular therapy in treating vascular trauma in the adult population is being
      extended to the pediatric population. We present a case of a 14-year-old male
      with an axillary artery injury that was diagnosed by computer tomography
      angiogram and treated with an endovascular Stent graft with 1-year follow-up.

PMID- 19159761
TI  - Division of the fistula in laparoscopic-assisted repair of anorectal
      malformations-are clips or ties necessary?
AB  - BACKGROUND: Laparoscopic-assisted anorectoplasty (LAARP) was introduced in 2000
      by Georgeson (J Pediatr Surg. 2000;35:927-930) and has gained interest because of
      improved visualization of the rectal fistula and the ability to place the pull
      through segment within the levator muscle complex with minimal dissection.
      Currently, there is no consensus on how the fistula should be managed during
      LAARP. We postulated that the fistula could be managed with simple division and
      temporary diversion of urine through a Foley catheter without surgical ligation
      of the fistula similar to the management of a traumatic urethral injury. METHODS:
      A retrospective chart review was performed of patients with imperforate anus who
      underwent LAARP between January 2005 and September 2007. RESULTS: Eight patients
      were managed with a LAARP. Five male patients had the fistula simply divided. In
      these 5 patients, the location of the fistula was rectoprostatic (2) and
      rectobulbar (3). The Foley catheter was left in position until a retrograde
      urethrogram demonstrated no evidence of a leak (range, 6-40 days). There were no
      postoperative urethral strictures and one diverticulum. Follow-up has ranged from
      10 to 19 months. CONCLUSION: Male patients with a rectourethral fistula at or
      just below the prostate can be safely and successfully managed with simple
      division of the fistula.

PMID- 19159762
TI  - Small bowel evisceration through the rectum in childhood. [letter].

PMID- 19159763
TI  - Ruptured fetal omphalocele complicated by midgut volvulus with strangulation.

PMID- 19159764
TI  - Flow injection based methods for fast screening of antioxidant capacity.
AB  - The role and importance of antioxidants in different fields, ranging from
      physiology to food technology, have become evident in the past years, requiring
      adequate analytical methodologies. Therefore, the determination of antioxidant
      capacity as a routine or screening analysis fosters its automation. In this
      context, several flow injection methods based on scavenging of 2,2'-azinobis-(3
      ethylbenzothiazoline-6-sulphonate) radical cation (ABTS(+)) or 2,2-diphenyl-1
      picrylhydrazyl radical (DDPH) or based on the determination of total reducing
      capacity have been proposed. The objective of the present review is to critically
      compare the different approaches, regarding their degree of automation, their
      performance vs. the respective batch procedure and its applicability to real
      samples.

PMID- 19159765
TI  - Chlorine gas sensors using one-dimensional tellurium nanostructures.
AB  - Tellurium nanotubes have been grown by physical vapor deposition under inert
      environment at atmospheric pressure as well as under vacuum conditions. Different
      techniques such as scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), X-ray diffraction (XRD) and optical absorption have been
      utilized for characterization of grown structures. Films prepared using both
      types of tellurium nanotubes were characterized for sensitivity to oxidizing and
      reducing gases and it was found that the relative response to gases depends on
      the microstructure. Nanotubes prepared at atmospheric pressure (of argon) showed
      high sensitivity and better selectivity to chlorine gas. Impedance spectroscopy
      studies showed that the response to chlorine is mainly contributed by grain
      boundaries and is therefore enhanced for nanotubes prepared under argon
      atmosphere.

PMID- 19159766
TI  - Liquid chromatographic fingerprint of 3-methylflavone-8-carboxylic acid
      established for its synthesis control analysis.
AB  - A high-performance liquid chromatographic method was proposed for the separation
      of relative impurities in industrial 3-methylflavone-8-carboxylic acid (MFCA) and
      its intermediate methyl 3-propionylsalicylate (MPS). Benzoic acid (BA), MPS, 6
      chloro-3-methylflavone-8-carboxylic acid (MFCA-Cl) and methyl 5-chloro-3
      propionylsalicylate (MPS-Cl) in MFCA, and MPS-Cl in MPS were respectively
      quantified by an external standard method. As results showed, the linearity of
      standard curves was excellent with the relative coefficients of over 0.999 for
      all the detected components, and the intra- and inter-day precisions of
      impurities determination were satisfactory with the relative standard deviation
      of not more than 8.0%. Under the selected experimental condition, the
      chromatographic fingerprints of MFCA and MPS were drawn synthetically, and the
      transfer of impurities in the stepwise reactions of MFCA manufacture was
      elucidated. The fingerprints have great potential in instructing the production
      of MFCA for industrial use and in conducting the conversion of relative
      impurities.

PMID- 19159767
TI  - Separation/preconcentration of trace amounts of Cr, Cu and Pb in environmental
      samples by magnetic solid-phase extraction with Bismuthiol-II-immobilized
      magnetic nanoparticles and their determination by ICP-OES.
AB  - A new method for separation/preconcentration of trace amounts of Cr, Cu and Pb in
      environmental samples by magnetic solid-phase extraction (SPE) with Bismuthiol-II
      immobilized magnetic nanoparticles and their determination by ICP-OES has been
      developed. The separation of the target analytes from the aqueous solution
      containing the target analytes and Bismuthiol-II-immobilized magnetic
      nanoparticles was simply achieved by applying external magnetic field. Optimal
      experimental conditions including pH, sample volume, eluent concentration and
      volume and co-existing ions have been studied and established. Under the optimal
      experimental conditions, the detection limits for Cr, Cu and Pb with enrichment
      factors of 96, 95 and 87 were found to be 0.043, 0.058 and 0.085 ngmL(-1) and
      their relative standard deviations (R.S.D.s) were 3.5%, 4.6% and 3.7% (n=5, C=2
      ngmL(-1)), respectively. The method was validated with certified reference
      material (GBW50009-88) of environmental water sample and the analytical results
      coincided well with the certified values. Furthermore, the method was
      successfully applied to the determination of target analytes in river and lake
      water samples. Compared with established methods, the proposed method is
      characterized with high enrichment factor, fast separation and low detection
      limits.

PMID- 19159768
TI  - Digital image-based flame emission spectrometry.
AB  - A digital image-based flame emission spectrometric (DIB-FES) method for the
      quantitative chemical analysis is proposed here for the first time. The DIB-FES
      method employs a webcam to capture the digital images which are associated to a
      radiation emitted by the analyte into an air-butane flame. Since the detection by
      webcam is based on the RGB (red-green-blue) colour system, a novel mathematical
      model was developed in order to build DIB-FES analytical curves and estimate
      figures of merit for the proposed method. In this approach, each image is
      retrieved in the three R, G and B individual components and their values were
      used to define a position vector in RGB three-dimensional space. The norm of this
      vector is then adopted as the RGB-based value (analytical response) and it has
      revealed to be linearly related to the analyte concentration. The feasibility of
      the DIB-FES method is illustrated in three applications involving the
      determination of lithium, sodium and calcium in anti-depressive drug,
      physiological serum and water, respectively. In comparison with the traditional
      flame emission spectrometry (trad-FES), no statistic difference has been observed
      between the results by applying the paired t-test at the 95% confidence level.
      However, the DIB-FES method has offered the largest sensitivities and precision,
      as well as the smallest limits of detection and quantification for the three
      analytes. These advantageous characteristics are attributed to the trivariate
      nature of the detection by webcam.

PMID- 19159769
TI  - Development of an optical ammonia sensor based on polyaniline/epoxy resin (SU-8)
      composite.
AB  - Polyaniline (PANI)/glycidyl ether of bisphenol A (SU-8) composite film is
      elaborated in order to detect ammonia gas. These composite films are
      characterized by ultraviolet-visible (UV-vis) spectroscopy, Fourier transformed
      infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The
      sensitivity to ammonia is measured by optical absorption changes. The ammonia
      sensing properties of PANI/SU-8 composite films are studied, and then are
      compared to pure PANI films elaborated by chemical way. Experimental results show
      that the PANI/SU-8 optical sensor has simultaneously a rapid response to ammonia
      gas and regenerates easily, that is advantageous compared to pure PANI films.

PMID- 19159771
TI  - Authentication of fattening diet of goat kid according to their fatty acid
      profile from perirenal fat.
AB  - Fatty acids of forty-two samples of perirenal fat of goat kids reared on three
      different feeding systems: goat milk (B), milk replacer (R) and milk-based
      starter (F) have been analyzed by Gas Chromatography flame ionization detector.
      The lipids were extracted by melting of perirenal fat in a microwave oven. The
      fat was then filtered and dissolved in hexane. This analysis was performed on a
      column (100 m x 0.25 mm i.d. and 0.25 microm film thickness) coated with a polar
      stationary phase HP-88 and flame ionization detector was used. Hydrogen (25 psi
      inlet constant pressure) was used as carrier gas. Programmed temperature was kept
      at 175 degrees C and held isothermally for 10 min, and was then raised to 205
      degrees C at a rate of 3 degrees C/min and held isothermally for 10 min. By using
      the fatty acids as chemical descriptors, pattern recognition techniques were
      applied to differentiate between goat milk, milk replacer and milk-based starter
      fattening diet of goat kid. C18:2 and C18:3 acids were found to be the most
      differentiating variables.

PMID- 19159770
TI  - In situ continuous derivatization/pre-concentration of carbonyl compounds with
      2,4-dinitrophenylhydrazine in aqueous samples by solid-phase extraction
      Application to liquid chromatography determination of aldehydes.
AB  - A rapid and straightforward continuous solid-phase extraction system has been
      developed for in situ derivatization and pre-concentration of carbonyl compounds
      in aqueous samples. Initially 2,4-dinitrophenylhydrazine, the derivatizing agent,
      was adsorbed on a C(18) mini-column and then 15-ml of sample were continuously
      aspirated into the flow system, where the derivatization and pre-concentration of
      the analytes (low-molecular mass aldehydes) were performed simultaneously.
      Following elution, 20 microl of the extract were injected into a LC-DAD system,
      in which hydrazones were successfully separated in 12 min on a RP-C(18) column
      using a linear gradient mobile phase of acetonitrile-water of 60-100%
      acetonitrile for 8 min, flowing at 0.5 ml/min. The whole analytical process can
      be accomplished within ca. 35 min. Under optimum conditions, limits of detection
      were obtained between 0.3 and 1.0 microg/l and RSDs (inter-day precision) from
      1.2 to 4.6%. Finally, some applications on water samples are presented with
      recoveries ranged from 95.8 to 99.4%.

PMID- 19159772
TI  - A LC-MS method allowing the analysis of HMX and RDX present at the picogram level
      in natural aqueous samples without a concentration step.
AB  - The introduction of chloroform into the nebulising gas of a LC/MS electrospray
      interface (ESI), in a perfectly controlled way, leads to the formation of intense
      adducts ([M+Cl](-)) when a mobile phase containing HMX (1,3,5,7-tetranitro
      1,3,5,7-tetrazacyclooctane or octogen) and RDX (1,3,5-trintro-1,3,5
      triazacyclohexane or hexogen) is eluted. This LC/MS method allows the direct
      analysis of aqueous samples containing HMX and RDX at the pictogram level without
      a concentration step. The method is used to determine HMX and RDX concentrations
      in ground water samples from a military site.

PMID- 19159773
TI  - Hybrid sequential injection-flow injection manifold for the spectrophotometric
      determination of total sulfite in wines using o-phthalaldehyde and gas-diffusion.
AB  - A new automated spectrophotometric method for the determination of total sulfite
      in white and red wines is reported. The assay is based on the reaction of o
      phthalaldehyde (OPA) and ammonium chloride with the analyte in basic medium under
      SI conditions. Upon on-line alkalization with NaOH, a blue product is formed
      having an absorption maximum at 630 nm. The parameters affecting the reaction -
      temperature, pH, ionic strength, amount concentration and volume of OPA, amount
      concentration of ammonium chloride, flow rate and reaction coil length - and the
      gas-diffusion process - sample and HCl volumes, length of mixing coil, donor flow
      rate - were studied. The proposed method was validated in terms of linearity (1
      40 mgL(-1), r=0.9997), limit of detection (c(L)=0.3 mgL(-1)) and quantitation
      (c(Q)=1.0 mgL(-1)), precision (s(r)=2.2% at 20 mgL(-1) sulfite, n=12) and
      selectivity. The applicability of the analytical procedure was evaluated by
      analyzing white and red wine samples, while the accuracy as expressed by recovery
      experiments ranged between 96% and 106%.

PMID- 19159774
TI  - Amperometric determination of cyanides at the low ppb level by automated
      preconcentration based on gas diffusion coupled to sequential injection analysis.
AB  - A simple, sensitive method for determining free cyanides is described. The assay
      is based on automated gas diffusion of the analyte using sequential injection
      analysis (SIA) coupled to amperometric detection on a silver working electrode.
      The effects of varying several parameters affecting the analytical procedure
      (including the flow rates of the donor and acceptor streams, the concentrations
      of the reagents and the sample volumes) were studied. The validity and quality of
      the method were also assessed, by examining its linearity, limits of detection
      and quantitation, precision, selectivity to potentially interfering substances.
      Its sensitivity can be enhanced by applying a simple preconcentration step,
      following which limits of detection were found to be 0.05-0.12 microgL(-1).
      Application of the proposed assay to the analysis of tap, mineral and table water
      samples spiked at concentrations ranging from 1 to 10 microgL(-1) CN(-), yielded
      satisfactory recoveries (88-112%).

PMID- 19159775
TI  - Phosphotriesterase: a complementary tool for the selective detection of two
      organophosphate insecticides: chlorpyrifos and chlorfenvinfos.
AB  - This work shows the possibility of combining the high sensitivity of genetically
      modified Drosophila melanogaster acetylcholinesterase (B394) with the ability of
      phosphotriesterase (PTE) to hydrolyse organophosphate compounds, in the aim of
      developing a biosensor selective to two insecticides of interest: chlorpyrifos
      and chlorfenvinfos. The studies clearly demonstrate that chlorfenvinfos is a
      substrate that acts as competitive inhibitor of PTE, therefore preventing the
      efficient hydrolysis of other pesticides, including chlorpyrifos. A bi-enzymatic
      sensor was designed by immobilizing both B394 and PTE in a polyvinylalcohol
      matrix. The sensor was shown to be able to discriminate between chlorpyrifos and
      chlorfenvinfos inhibitions.

PMID- 19159776
TI  - Improved design for high resolution electrospray ionization ion mobility
      spectrometry.
AB  - An improved design for high resolution electrospray ionization ion mobility
      spectrometry (ESI-IMS) was developed by making some salient modifications to the
      IMS cell and its performance was investigated. To enhance desolvation of
      electrospray droplets at high sample flow rates in this new design, volume of the
      desolvation region was decreased by reducing its diameter and the entrance
      position of the desolvation gas was shifted to the end of the desolvation region
      (near the ion gate). In addition, the ESI source (both needle and counter
      electrode) was positioned outside of the heating oven of the IMS. This
      modification made it possible to use the instrument at higher temperatures, and
      preventing needle clogging in the electrospray process. The ion mobility spectra
      of different chemical compounds were obtained. The resolving power and resolution
      of the instrument were increased by about 15-30% relative to previous design. In
      this work, the baseline separation of the two adjacent ion peaks of morphine and
      those of codeine was achieved for the first time with resolutions of 1.5 and 1.3,
      respectively. These four ion peaks were well separated from each other using
      carbon dioxide (CO(2)) rather than nitrogen as the drift gas. Finally, the
      analytical parameters obtained for ethion, metalaxyl, and tributylamine indicated
      the high performance of the instrument for quantitative analysis.

PMID- 19159777
TI  - Excitation-emission-kinetic fluorescence coupled with third-order calibration for
      quantifying carbaryl and investigating the hydrolysis in effluent water.
AB  - A novel method for determination of carbaryl in effluent was proposed in this
      study. The kinetic evolution of excitation-emission matrix fluorescence (EEM) for
      the pesticide were recorded and come into being a four-way data array. The four
      way fluorescence data were analyzed using the parallel factor analysis (PARAFAC).
      The methodology exploits the second-order advantage of three-order calibration
      based on quadrilinear parallel factor analysis, allowing analyte concentrations
      to be estimated even in the presence of an uncalibrated fluorescent background.
      It gave the satisfactory results for determination of the carbaryl in effluent
      samples. In addition, the kinetic study of degradation of carbaryl was performed
      according to the kinetic profile provided by the calibration.

PMID- 19159778
TI  - Deoxyribonucleic acid modified poly(dimethylsiloxane) microfluidic channels for
      the enhancement of microchip electrophoresis.
AB  - In this paper, deoxyribonucleic acid (DNA) was employed to construct a functional
      film on the PDMS microfluidic channel surface and apply to perform
      electrophoresis coupled with electrochemical detection. The functional film was
      formed by sequentially immobilizing chitosan and DNA to the PDMS microfluidic
      channel surface using the layer-by-layer assembly. The polysaccharide backbone of
      chitosan can be strongly adsorbed onto the hydrophobic PDMS surface through
      electrostatic interaction in the acidic media, meanwhile, chitosan contains one
      protonatable functional moiety resulting in a strong electrostatic interactions
      between the surface amine group of chitosan and the charged phosphate backbone of
      DNA at low pH, which generates a hydrophilic microchannel surface and reveals
      perfect resistance to nonspecific adsorption of analytes. Aminophenol isomers (p
      , o-, and m-aminophenol) served as a separation model to evaluate the effect of
      the functional PDMS microfluidic chips. The results clearly showed that these
      analytes were efficiently separated within 60s in a 3.7 cm long separation
      channel and successfully detected on the modified microchip coupled with in
      channel amperometric detection mode at a single carbon fiber electrode. The
      theoretical plate numbers were 74,021, 92,658 and 60,552 Nm(-1) at the separation
      voltage of 900 V with the detection limits of 1.6, 4.7 and 2.5 microM (S/N=3) for
      p-, o-, and m-aminophenol, respectively. In addition, this report offered an
      effective means for preparing hydrophilic and biocompatible PDMS microchannel
      surface, which would facilitate the use of microfluidic devices for more
      widespread applications.

PMID- 19159779
TI  - Size-dependent electrochemiluminescence behavior of water-soluble CdTe quantum
      dots and selective sensing of l-cysteine.
AB  - Water-soluble CdTe quantum dots (QDs) with five sizes (2.25, 2.50, 2.77, 3.12,
      and 3.26nm) were synthesized with the hydrothermal method. The
      electrochemiluminescence (ECL) of CdTe QDs was investigated in detail in air
      saturated solution without adding foreign oxidant. It was found that the ECL of
      CdTe QDs displayed a size-dependent property. With the increasing in the particle
      size of the CdTe QDs, the ECL intensity was gradually increased, in addition,
      both ECL peak potentials and ECL onset potentials of CdTe QDs were shifted
      positively. Influences of some factors on the ECL intensity were investigated.
      Under the optimal conditions, the ECL intensity had a linear relationship with
      the concentration of l-cysteine (l-Cys) in the range from 1.3 x 10(-6) to 3.5 x
      10(-5) molL(-1) (R(2) 0.996) with a detection limit of 8.7 x 10(-7) molL(-1)
      (S/N=3). The proposed method was applied to the determination of l-Cys in real
      samples with satisfactory results. Compared with previous reports, it has better
      selectivity for the determination of l-Cys.

PMID- 19159780
TI  - Classification of edible vegetable oils using square wave voltammetry with
      multivariate data analysis.
AB  - This paper proposes a simple and non-expensive electroanalytical methodology for
      classification of edible vegetable oils with respect to type (canola, sunflower,
      corn and soybean) and conservation state (expired and non-expired shelf life).
      The proposed methodology employs an alcoholic extraction procedure followed by
      square wave voltammetry (SWV). Two chemometric methods were compared for
      classification of the resulting voltammograms, namely Soft Independent Modelling
      of Class Analogy (SIMCA) and Linear Discriminant Analysis (LDA) with variable
      selection by the Successive Projections Algorithm (SPA). The results were
      evaluated in terms of errors in a set of samples not included in the modelling
      process. The best results were obtained with the SPA-LDA method, which correctly
      classified all samples in terms of type and conservation state.

PMID- 19159781
TI  - Enhanced separation of seven quinolones by capillary electrophoresis with silica
      nanoparticles as additive.
AB  - This paper describes the enhanced separation of lomefloxacin, sparfloxacin,
      fleroxacin, norfloxacin, ofloxacin, gatifloxacin and pazufloxacin by capillary
      zone electrophoresis (CZE) using silica nanoparticles (SiNPs) as running buffer
      additive. The impact of SiNPs concentration on the resolution and selectivity of
      separation was investigated and a given value of SiNPs was finally chosen under
      the optimum conditions. The addition of the SiNPs to the running buffer enabled
      electroosmotic flow (EOF) decrease and permitted full interaction between SiNPs
      and analytes. The influence of separation voltage, pH and buffer concentration on
      the separation in the presence of SiNPs was examined. Interactions between drugs
      and nanoparticles during the separation are discussed; the determination of
      interaction constants is also achieved. A good resolution of seven quinolones was
      obtained within 15 min in a 50 cm effective length fused-silica capillary at a
      separation voltage of +10 kV in a 12 mM disodium tetraborate-phosphate buffer (pH
      9.08) containing 5.2 microgmL(-1) SiNPs.

PMID- 19159782
TI  - H2S sensing properties of nanocrystalline Sr2Fe(0.6)Ni(0.4)MoO6 thick film
      prepared by sol-gel citrate method.
AB  - Nanocrystalline Sr(2)FeMoO(6) (SFMO) belonging to the group of double perovskite
      oxides, was prepared by the sol-gel citrate method. The structural and
      microstructural characterization has been carried out with the help of X-ray
      diffraction (XRD) and transmission electron microscopy (TEM), respectively. XRD
      of Sr(2)Fe(1-x)Ni(x)MoO(6) (SFNMO) shows the formation of solid solution with
      average grain size of about 40nm. A comparative study of gas sensing behaviour of
      Sr(2)FeMoO(6) and Sr(2)Fe(1-x)Ni(x)MoO(6) with reducing gases like hydrogen
      sulfide (H(2)S), liquid petroleum gas (LPG), hydrogen (H(2)), ethanol
      (C(2)H(5)OH) and carbon monoxide (CO) were also discussed. The sensitivity is
      calculated by measuring the change the resistance of the sensor material in the
      presence of gas. Among the different composition of x (x=0.2, 0.3, 0.4, 0.5),
      Sr(2)Fe(0.6)Ni(0.4)MoO(6) (x=0.4) shows better response to H(2)S gas at 260
      degrees C. Incorporation of palladium (Pd) improves the gas response,
      selectivity, response time and reduced the operating temperature from 260 to 220
      degrees C for H(2)S gas.

PMID- 19159783
TI  - High-resolution surface plasmon resonance sensors based on a dove prism.
AB  - Wavelength interrogation surface plasmon resonance (SPR) spectroscopy using a
      dove prism combines a simple and inexpensive optical design with high-resolution
      refractive index monitoring and biosensing. A BK7 dove prism inverts an optical
      image with a total internal reflection angle of 72.8 degrees , an angle active in
      SPR. Hence, a unique system can accomplish SPR biosensing using wavelength
      interrogation and also perform SPR imaging. This optical configuration
      advantageously uses a single axis optical path between each optical component,
      simplifying the optical design of SPR instruments without compromise of the
      analytical performance. Fluidics were also incorporated to the instrument design
      for efficient sample delivery. The SPR instrument is characterized in terms of
      refractive index (RI) sensitivity, RI resolution, reproducibility, and
      application for monitoring low concentration biological events. Data analysis
      methodologies are compared for improved resolution of the measured response. Raw
      data analyzed using a minimum hunting procedure results in RI resolution in the
      10(-6) range, while pre-treating data with singular value decomposition improves
      the resolution by one order of magnitude. Depending on the spectrophotometer
      employed, the RI range accessible can be easily tuned; examples with a 550-850 nm
      and a 550-1100 nm spectrophotometers are shown and results respectively in RI
      ranges of 1.32-1.39 RIU and 1.32-1.42 RIU. Monitoring of microM concentration of
      beta-lactamase is performed using the wavelength interrogation configuration of
      the biosensor. Finally, a SPR image of a surface with a water droplet (volume=500
      nL) was obtained using the dove prism SPR with a band pass filter and a CCD
      camera. SPR using a dove prism configuration combines advantages of portable SPR
      instruments, SPR imagers and research-grade SPR instruments in a unique platform.

PMID- 19159784
TI  - Chemical activation of egg shell membrane for covalent immobilization of enzymes
      and its evaluation as inert support in urinary oxalate determination.
AB  - Egg shell membrane is a novel, robust, microporous, cost effective, easily
      available organic support material. In recent studies egg shell membranes were
      utilized as organic support for enzyme immobilization. But low conjugation yield
      limits its application as good support for biotechnological industries. In
      present study egg shell membrane was chemically treated to introduce free
      functional groups for covalent linkage of proteins to increase its conjugation
      yield and stability of conjugate complex. Many enzymes were tested for
      immobilization on modified egg shell membrane like oxalate oxidase, glucose
      oxidase, peroxidase and lipase. A fifteen to sixteen fold increase in conjugation
      yield was observed when immobilization was performed after chemical treatment in
      comparison to immobilization on native membrane with slight change in specific
      activity of immobilized enzyme which ranges from 5% to 15%. Egg shell membrane
      bound enzymes showed slight changes in their kinetic properties after
      immobilization. Egg shell membrane bound oxalate oxidase shows detection limit of
      1.5 microM when used for urinary oxalate determination. Egg shell membrane
      support shows no interference to enzyme activity and a good correlation of 0.99
      was observed with the values estimated using commercially available Sigma kit.
      The immobilized oxalate oxidase, glucose oxidase, peroxidase and lipase were
      stable up to duration of 180 days and there is respective loss of 10%, 13%, 24%,
      and 33% of initial activity. Overall result strengthens our view of using
      chemically modified egg shell membrane as solid support for better immobilization
      of enzymes and can be used in various biotechnological applications.

PMID- 19159785
TI  - Silver UPD ultra-thin film modified nanoporous gold electrode with applications
      in the electrochemical detection of chloride.
AB  - Nanoporous noble metals are usually expected to exhibit much higher surface areas
      than smooth ones, making them of particular importance in many electrochemical
      applications. This paper describes a simple electrochemical method to modify a
      nanoporous Au (NPG) surface by using an under potentially deposited (UPD) Ag
      adlayer. The NPG electrode was obtained by the dealloying of Zn from Au(x)Zn(1-x)
      in a 40-60mol% zinc chloride-1-ethyl-3-methylimidazolium chloride (ZnCl(2)-EMIC)
      ionic liquid. The Ag UPD modified nanoporous gold (NPG/Ag(UPD)) electrode
      possessed dual properties, including an intrinsic high surface area from the
      nanoporous structure and the characteristics of the Ag UPD adlayer. The potential
      utility of using NPG/Ag(UPD) for sensors was demonstrated by its excellent
      sensitivity and selectivity in the electrochemical determination of chloride
      ions. An atomic scale metal monolayer obtained in the UPD process was selected as
      a sensing agent. The long-term storability and operational stability of the
      electrode were strongly demonstrated. Specifically, two couples of redox waves at
      approximately 552mV and approximately 272mV, respectively, were observed in the
      cyclic voltammograms (CVs) of the NPG/Ag(UPD) after the adsorption of chloride
      ions. The first couple of redox waves was related to the UPD and silver stripping
      and the second couple of redox waves was induced by the adsorption of Cl(-). The
      Cl(-) adsorption process on the NPG/Ag(UPD) electrode followed the transient
      Langmuir adsorption kinetic model. The ratio of the integrated charges for these
      two anodic stripping peaks was selectively used to determine dilute chloride ion
      levels. The calibration curve was linear in the Cl(-) concentration range of 0.5
      30.0muM.

PMID- 19159786
TI  - Rapid determination of Delta9-Tetrahydrocannabinol in saliva by polymer monolith
      microextraction combined with gas chromatography-mass spectrometry.
AB  - A method was developed for the determination of Delta(9)-Tetrahydrocannabinol
      (THC) in saliva by polymer monolith microextraction (PMME) combined with gas
      chromatography-mass spectrometry. The poly(methacrylic acid-co-ethylene glycol
      dimethacrylate) (p(MAA-co-EGDMA)) monolithic capillary column was selected as the
      extraction medium of PMME, which showed high extraction capacity towards THC in
      saliva. To reach optimum PMME extraction performance, several PMME parameters
      were investigated, including matrix pH, flow rate for extraction, sampling volume
      and elution solvent. Under the optimal conditions, good extraction efficiency was
      obtained with no matrix interference in the process of extraction and the
      subsequent GC-MS analysis. In the selected-ion monitoring (SIM) mode, the limit
      of detection (LOD) for THC was 0.68 ng/mL. The linearity range of the method was
      3-300 ng/mL. Excellent reproducibility of the method was exhibited by intra- and
      inter-day precisions, yielding the relative standard deviations (R.S.D.s) less
      than 12%; recoveries higher than 89%. The proposed method was proved to be rapid,
      sensitive, and competently applied to the determination of THC in saliva samples.

PMID- 19159788
TI  - Standard addition analysis of fluoroquinolones in human serum in the presence of
      the interferent salicylate using lanthanide-sensitized excitation-time decay
      luminescence data and multivariate curve resolution.
AB  - Three fluoroquinolone antibiotics (ciprofloxacin, norfloxacin and danofloxacin)
      have been determined in human serum in the presence of the potential interferent
      salicylate, by processing lanthanide-sensitized excitation-time decay matrix data
      for their terbium (III) complexes. The algorithm employed, multivariate curve
      resolution-alternating least-squares, is one of the few methodologies which
      permit the achievement of the second-order advantage in the presence of a high
      degree of overlapping between the time decay profiles for the analyte and the
      interferent complexes. Furthermore, the presence of analyte-background
      interactions makes it necessary to employ the standard addition method for
      successful quantitation. Both simulations and experiments showed that the
      modified standard addition method was suitable for this purpose, in which the
      test data matrix was subtracted from the standard addition matrices, and
      quantitation proceeded using classical external calibration procedure. The
      analyte concentration ranges were all within the therapeutic range, i.e., 0-6
      mgL(-1) in serum, with final concentrations in the measuring cell in the order of
      0.2 mgL(-1).

PMID- 19159787
TI  - Synthesis and spectral characteristics of two novel intramolecular charge
      transfer fluorescent dyes.
AB  - The synthesis and absorption/fluorescence properties of two novel intramolecular
      charge transfer (ICT) compounds of (fluorene-2-yl)-(9-ethylcarbazole-3-yl) ketene
      and 1-phenyl-3-(fluorenone-2-yl)-5-(9-ethylcarbazole-3-yl)-2-pyrazoline were
      reported. The primary structure of the target compounds was characterized by IR
      and (1)H NMR. The systems contained a fluorenone or a propenon group as an
      electron acceptor (A) and an N-ethylcarbazole and a pyrazoline group as electron
      donors (D). From the emissive properties it was concluded that the electronic
      coupling between D and A was sufficient to allow charge transfer in these
      molecules. The ICT maximal emission displayed a large wavelength shift and Stokes
      shifts increased in response to the increase of the solvent polarity. The highly
      solvatochromic properties made the two compounds of great interest as new classes
      of fluorescent probes, electroluminescent and electrofax materials.

PMID- 19159789
TI  - Preliminary study of UV ageing process of proteinaceous paint binder by FT-IR and
      principal component analysis.
AB  - This work presents a preliminary study on the ageing process of proteinaceous
      binder materials used in painting under UV light. With this aim, two sets of
      model samples were prepared: samples prepared using a single protein material and
      complex samples prepared in a similar way to the sequence of layers in a real
      painting from lowest to highest complexity (protein, drying oils, pigment and
      varnish). The study focuses on acquiring information about the possible
      degradation process of proteinaceous binders due to ageing and how this process
      be affected by the presence of characteristic non-proteinaceous painting
      materials, such as lipids from linseed oil, terpenic compounds from varnish and
      inorganic pigments. Samples simulated the accelerated ageing process, as did the
      UV light exposition. The FT-IR spectra were recorded after 100, 500, 1000 and
      1500 h of exposition. The study of the accelerated ageing process was performed
      by means of principal component analysis (PCA) using the FT-IR spectra obtained.
      Loadings from the significant principal components were analysed to find the FT
      IR frequency (cm(-1)) involved in the degradation process. The study showed the
      lack of any relevant modification on the proteins in the single model samples. On
      the contrary, the complex model samples showed the ageing process. The
      accelerated ageing process can be explained by a principal component from PCA.
      The most affected IR region was 2900-3600 cm(-1), where the amide band was
      included.

PMID- 19159790
TI  - Application of tandem column solid phase extraction and flame atomic absorption
      spectrometry for the determination of inorganic and organically bound forms of
      iron in wine.
AB  - A tandem column solid phase extraction (SPE) procedure has been devised to
      examine the fractionation of Fe in wine. Wine was filtered through a 0.45 microm
      filter and then, the filtrate was driven through an adsorbing Amberlite XAD-7HP
      column followed by a cation exchange Dowex 50 W-x8-200 column. Three different Fe
      groupings are discriminated and assessed, including hydrophobic species of Fe
      bound to phenolic substances and related species (phenolic fraction), cationic
      species comprising simple Fe ions and labile Fe forms (cationic fraction), in
      addition to anionic and/or neutral Fe complexes with organic acids (residual
      fraction). The suitability of the procedure has been evaluated analyzing four
      bottled red wines. The results obtained were verified using another tandem column
      assemblage in which an adsorbing Amberlite XAD-16 column was exchanged by the
      Amberlite XAD-7HP column. The fractionation pattern ascertained for Fe in
      analyzed wines is discussed in reference to previously published works. In
      addition, a conditioning treatment and preparation of Amberlite XAD resins have
      been revised.

PMID- 19159791
TI  - Flow injection analysis system based on amperometric thin-film transducers for
      free chlorine detection in swimming pool waters.
AB  - This work reports on the performance of a user-friendly flow injection analysis
      (FIA) system for the monitoring of free chlorine. A methacrylate flow cell
      integrating a gold thin-film microelectrode, together with an on-chip gold
      counter electrode, both fabricated by microfabrication technology, provided
      robustness, low output impedance, rapid response and low cost to the proposed
      flow system. An external Ag/AgCl reference electrode placed downstream the chip
      completes the electrochemical cell. Amperometric detection of chlorine was
      carried out at a set potential of +350 mV, without oxygen interference. The
      proposed flow system responded linearly to chlorine concentrations in a range
      from 0.2 to 5 mgl(-1), with a sensitivity of 0.23 microAlmg(-1), the estimated
      limit of detection being 0.02 mgl(-1). In addition, the system response was kept
      stable for at least 10 days (+/-3sigma criterion), by keeping the flow system in
      an inert atmosphere when not in use. Fifteen samples of swimming pool waters were
      analyzed and no matrix effects were detected. Also, results were in good
      agreement with those obtained by a standard method. The excellent analytical
      performance of the system together with its good working stability would also
      enable its application for the detection of chlorine in other matrices such as
      tap water or chlorine stock solutions.

PMID- 19159792
TI  - Increasing the sensitivity of the spectrophotometric determinations of the oxygen
      content in YBCO superconducting samples using the I(3-)-starch compound.
AB  - The conditions for formation of the I(3)(-)-starch compound and measuring its
      absorbance have been found, and a spectrophotometric method has been developed
      for the determination of the oxygen content in YBa(2)Cu(3)O(y) superconducting
      bulk samples. The method involves the following stages: a decomposition of the
      sample in an acid medium in the presence of iodide ions under inert atmosphere;
      formation of a complex between Cu(II) and glycine; binding the I(3)(-)-complex
      with a starch and the absorbance measurement of the colored I(3)(-)-starch
      compound. The coefficient of the active oxygen is calculated by the ratio of the
      absorbances of two solutions and the method does not require both calibration and
      precise measuring sample mass. The accuracy of the results is confirmed applying
      the comparative spectrophotometric method that uses the yellow I(3)(-)-complex.
      The precision of the results evaluated by the relative standard deviation is 2%.
      The developed method is sensitive and allows a sample mass about 2mg to be used.
      The analysis is rapid and requires a simple and inexpensive apparatus. Thus the
      new method would be useful for an express analytical control of the oxygen
      content of YBCO-superconducting materials produced for the electronics.

PMID- 19159793
TI  - Infrared study of aging of edible oils by oxidative spectroscopic index and MCR
      ALS chemometric method.
AB  - One of the most suitable analytical techniques used for edible oil quality
      control is Fourier transform mid infrared spectroscopy (FT-MIR). FT-MIR
      spectroscopy was used to continuously characterize the aging of various edible
      oils thanks to a specific aging cell. There were differences in the spectra of
      fresh and aged oils from different vegetable sources, which provide the basis of
      a method to classify them according to the oxidative spectroscopic index value.
      The use of chemometric treatment such as multivariate curve resolution
      alternative least square (MCR-ALS) made it possible to extract the spectra of
      main formed and degraded species. The concentration profiles gave interesting
      information about the ability of the various oils to support the oxidative
      treatment and showed that all oils present the same aging process. Both methods
      led to concordant results in terms of induction times determined by the oxidative
      spectroscopic index and the appearance of oxidation products revealed by MCR-ALS.

PMID- 19159794
TI  - Thermally induced electrode protection against biofouling.
AB  - This paper demonstrates that a combined thermal and electrochemical conditioning
      step can greatly minimize electrode blocking. We detected 50 ppm dopamine after a
      blocking step in 1000 ppm gelatine solution. Only a treatment of the electrode at
      -1.5 V and 61.5 degrees C can reveal the voltammetric dopamine signals to 82%.
      The increase of the peak separation of the cyclic voltammograms obtained in 50
      ppm dopamine is limited to 14%, whereas negative polarization (-1.5 V) alone
      leads to a 31% increase compared to 109% upon thermal and 105% without any
      conditioning. The positive effects can be addressed to an enforced reductive
      degradation and accelerated removal of the blocking agents. Also the formation of
      hydrogen bubbles might play a significant role. Thermo-electrochemical treatment
      holds great promise for electrochemical sensors and detectors which are applied
      for long-term monitoring of samples that contain blocking matrices.

PMID- 19159795
TI  - Diimine ligand as a novel chemiluminescence enhancer of luminol-containing
      compounds.
AB  - A series of diimine ligands (DLs) have been synthesized and evaluated for their
      non-enzymatic chemiluminescence (CL) enhancement of isoluminol or luminol
      containing compounds. Of the DLs, N,N'-bis(m-hydroxylbenzylidene)propylenediamine
      (DL 10) was found to greatly enhance their CLs approximately 40 folds for
      isoluminol, 10 folds for luminol and 6 folds for a luminol-containing polymer.
      The CL enhancement of the compounds was observed in the presence of CH(3)CN,
      H(2)O(2), tetra-n-propylammonium hydroxide (TPA), and Fe (III) ion. The possible
      mechanism of this CL enhancement was discussed on the basis of the chelate
      formation of the ligand and the metal ions.

PMID- 19159796
TI  - Immobilization of trypsin on silica-coated fiberglass core in microchip for
      highly efficient proteolysis.
AB  - In this report, trypsin was immobilized on silica-coated fiberglass core in
      microchip to form a core-changeable bioreactor for highly efficient proteolysis.
      To prepare the fiber core, a layer of organic-inorganic hybrid silica coating was
      prepared on the surface of a piece of glass fiber by a sol-gel method with
      tetraethoxysilane (TEOS) and 3-aminopropyltriethoxysilane (APTES) as precursors.
      Subsequently, trypsin was immobilized on the coating with the aid of
      glutaraldehyde. Prior to use, the enzyme-immobilized fiber was inserted into the
      channel of a microchip to form an in-channel fiber bioreactor. The novel
      bioreactor can be regenerated by changing its fiber core. The scanning electron
      microscopy images of the cross-section of a trypsin-immobilized fiber indicated
      that a layer of approximately 1mum thick film formed on the glass substrate. The
      feasibility and performance of the unique bioreactor were demonstrated by the
      tryptic digestion of bovine serum albumin (BSA) and cytochrome c (Cyt-c) and the
      digestion time was significantly reduced to less than 10s. The digests were
      identified by MALDI-TOF MS with sequence coverages of 45% (BSA) and 77% (Cyt-c)
      that were comparable to those obtained by 12-h conventional in-solution tryptic
      digestion. The fiber-based microchip bioreactor provides a promising platform for
      the high-throughput protein identification.

PMID- 19159797
TI  - Preconcentration of nickel and cadmium by TiO2 nanotubes as solid-phase
      extraction adsorbents coupled with flame atomic absorption spectrometry.
AB  - TiO(2) nanotubes, a new nanomaterial, are often used in the photocatalysis. Due
      to its relatively large specific surface areas it should have a higher enrichment
      capacity. However, very few applications in the enrichment of pollutants were
      found. This paper described a new procedure to investigate the trapping power of
      TiO(2) nanotubes with cadmium and nickel in water samples as the model analytes
      and flame atomic absorption spectrometry for the analysis. The possible
      parameters influencing the enrichment were optimized. Under the optimal SPE
      conditions, the method detection limits and precisions (R.S.D., n=6) were 0.25
      ngmL(-1) and 2.2% for cadmium, 1 ngmL(-1) and 2.6% for nickel, respectively. The
      established method has been successfully applied to analyze four realworld water
      samples, and satisfactory results were obtained. The spiked recoveries were in
      the range of 90.2-99.2% for them. All these indicated that TiO(2) nanotubes had
      great potential in environmental field.

PMID- 19159798
TI  - Comparison of tungsten coil electrothermal vaporization and thermospray sample
      introduction methods for flame furnace atomic absorption spectrometry.
AB  - Flame furnace atomic absorption spectrometry (FF-AAS) is a newly developed flame
      atomic absorption spectrometric technique based on arranging a flame furnace onto
      the top of the flame burner head. In this fundamental investigation, 25 elements
      were carefully tested by using either thermospray FF-AAS or tungsten coil
      electrothermal vaporization FF-AAS, of which 15 volatile and semi-volatile
      elements (Cd, Tl, Ag, Pb, Zn, Hg, Cu, Sb, Bi, Te, In, As, Se, Sn and Au)
      exhibited better limits of detection compared to those by conventional FAAS;
      however, non-volatile or refractory elements (Fe, Co, Ni, Cr, Mn, Pd, Pt, Al, Be
      and V) showed inferior sensitivities by the proposed methods.

PMID- 19159799
TI  - Development of a highly sensitive and specific monoclonal antibody-based enzyme
      linked immunosorbent assay (ELISA) for detection of Sudan I in food samples.
AB  - The use of Sudan I as an additive in food products has been prohibited in the
      European Union and many other countries. In this study, a highly sensitive and
      specific monoclonal antibody (mAb)-based indirect competitive enzyme-linked
      immunosorbent assay (ELISA) for the detection of Sudan I in food samples was
      developed. The hapten derivative with a three-carbon-atom length of carboxylic
      spacer at the azobound para-position was synthesized and coupled to carrier
      proteins. The hapten-bovine serum albumin (BSA) conjugate was used as an
      immunogen, while the hapten-ovalbumin (OVA) conjugate was applied as a coating
      antigen. The mAb against Sudan I was produced by hybridoma technique and the
      corresponding ELISA was characterized in terms of sensitivity, specificity,
      precision and accuracy. At optimal experimental conditions, the standard curve
      was constructed in concentrations of 0.1-100 ngmL(-1). The values of IC(50) for
      nine standard curves were in the range of 1.1-2.0 ngmL(-1) and the LOD at a
      signal-to-noise ratio of 3 (S/N=3) was 0.07-0.14 ngmL(-1). The cross-reactivity
      values of the mAb with Sudan II, III and IV were 9.5%, 33.9% and 0.95%; no cross
      reactivity was found with other six edible colorants: Lemon yellow, Bright blue,
      Indigotin, Kermes, Amarant and Sunset yellow, indicating the assay displays not
      only high sensitivity but also high specificity as well. The organic solvent
      effect on the assay was tested. It was observed that the ELISA was tolerated to
      30% of methanol and 10% of acetonitrile without significant loss of IC(50) value.
      Six food samples were spiked with Sudan I and the methanolic extracts after
      appropriate dilution were analyzed by ELISA. Acceptable recovery rates of 88.2
      110.5% and coefficients of variation of 2.5-17.4% were obtained. The ELISA for
      nine spiked samples was confirmed by high-performance liquid chromatography
      (HPLC) with a high correlation coefficient of 0.9840 (n=9). The mAb-based ELISA
      proven to be a feasible quantitative/screening method for Sudan I analysis in
      food samples with the properties of high sensitivity, specificity, simplicity of
      sample pretreatment, high sample throughput and low expense.

PMID- 19159800
TI  - A simple capillary electrophoresis with electrochemical detection method for
      determination of the hydrolysis rate constant of chlorogenic acid.
AB  - A method based on the kinetics stability study on hydrolysis of chlorogenic acid
      by capillary zone electrophoresis with electrochemical detection (CE-ED) has been
      developed in this paper. Both cyclic and hydrodynamic voltammograms of
      chlorogenic acid and its hydrolysis product caffeic acid have been investigated.
      The conditions for separation of chlorogenic acid and caffeic acid, such as the
      buffer pH and concentration, the separation voltage, and the injection time have
      been optimized. Under the optimum CE running conditions, the effects of reaction
      temperature and pH values of the hydrolysis solutions on the hydrolysis rate
      constants were further studied. The hydrolysis rate constants of chlorogenic acid
      were obtained from the concentration change of hydrolysis during the process of
      hydrolysis. Based on the fact, a simple and economical method for the
      determination of the hydrolysis rate constant and activation energy of hydrolysis
      reaction has been developed.

PMID- 19159801
TI  - Characterization of 2-phenylbenzo[g]quinoxaline derivatives as viscosity
      sensitive fluorescent probes.
AB  - To develop viscosity-sensitive fluorescent probes, five different substituted 2
      phenylbenzo[g]quinoxaline derivatives (3a-e) were designed and synthesized by
      using benzo[g]quinoxaline as a fluorophore and phenyl ring bearing a rotatable
      single bond as a viscosity-sensitive unit. The fluorescence properties of these
      compounds were investigated in the media of the ethylene glycol-glycerol mixture
      with varied viscosity. It is found that 2-(4-hydroxyphenyl)benzo[g]quinoxaline
      (3d) and 2-(4-dimethylaminophenyl)-benzo[g]quinoxaline (3e) carrying stronger
      electron-donating groups in the phenyl ring show more sensitive fluorescence
      response to viscosity, revealing their potential use in viscosity detection and
      the key role of the substituted groups. The effects of solvent polarity and pH on
      the fluorescent properties of 3d and 3e were also discussed. The present study
      might be useful in developing viscosity-sensitive fluorescent probes.

PMID- 19159802
TI  - Studies on the aconitine-type alkaloids in the roots of Aconitum Carmichaeli
      Debx. by HPLC/ESIMS/MS(n).
AB  - Studies of aconitine-type alkaloids in the Chinese herb Aconitum Carmichaeli were
      performed by HPLC/ESIMS/MS(n) and FTICR/ESIMS in positive ion mode. The
      characteristic fragmentation pathways in the MS(n) spectra were summarized based
      on previously published research literature and further study. According to the
      fragmentation pathways of mass spectrometry, results from the analysis of
      standard compounds and reports from literature, 111 compounds were identified or
      deduced in a total of 117 found compounds in A. Carmichaeli. In the 11 monoester
      diterpenoid alkaloids (MDA), 10 diesterditerpenoid alkaloids (DDA) and 81 lipo
      alkaloids, the novel alkaloids including 1 MDA, 2 DDA and 48 lipo-alkaloids were
      detected. In addition, 1 DDA, 7 lipo-alkaloids and 2 alkaloids with small
      molecular weights that possess C19-norditerpenoid skeleton were reported in A.
      Carmichaeli for the first time.

PMID- 19159803
TI  - Fluorescence detection of total count of Escherichia coli and Staphylococcus
      aureus on water-soluble CdSe quantum dots coupled with bacteria.
AB  - The aim of this paper was to demonstrate a fluorescence measurement method for
      rapid detection of two bacterial count by using water-soluble quantum dots (QDs)
      as a fluorescence marker, and spectrofluorometer acted as detection apparatus,
      while Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were as
      detection target bacteria. Highly luminescent water-soluble CdSe QDs were first
      prepared by using thioglycolic acid (TGA) as a ligand, and were then covalently
      coupled with target bacteria. The bacterial cell images were obtained using
      fluorescence microscopy. Our results showed that CdSe QDs prepared in water phase
      were highly luminescent, stable, and successfully conjugated with E. coli and S.
      aureus. The fluorescence method could detect 10(2)-10(7)CFU/mL total count of E.
      coli and S. aureus in 1-2h and the low detection limit is 10(2)CFU/mL. A linear
      relationship of the fluorescence peak intensity and log total count of E. coli
      and S. aureus have been established using the equation Y=118.68X-141.75
      (r=0.9907).

PMID- 19159804
TI  - Sensing parts per million levels of gaseous NO2 by a optical fiber transducer
      based on calix[4]arenes.
AB  - Calixarenes are interesting building blocks in supramolecular receptor design.
      They can be easily functionalized to give the desired guest binding and
      sequestration properties. We demonstrate here the use of simple alkylated
      calixarenes as novel NO(2) sensors. Upon reacting with gaseous NO(2), alkylated
      calixarenes form stable calixarene-NO(+) (nitrosonium) complexes that have a deep
      purple color. This specific and selective formation of the colored complex was
      used to develop a fiber optic based colorimetric NO(2) sensor. Several alkylated
      calixarenes are used and tested as sensing materials. The calixarene compound was
      immobilized on a fine mesh silica-gel coated thin layer chromatography plate. The
      sensing plate was coupled with a fiber optic based photodetector. Gas samples
      were sampled in a manner where they impinged on the surface of sensing plate. The
      light transmission through the plate was continuously monitored. For a 5 min
      sample, the limit of detection was 0.54 ppmv with 1,3-alternate O-hexyl
      calix[4]arene (1a). There were no significant response differences between
      different conformations of calixarenes such as 1,3-alternate or cone. This
      chemistry can form the basis of a colorimetric sensor that relies on extant
      filter tape technology. With calixarenes however, such a reaction is potentially
      reversible - color formed upon reaction with NO(2) can be reversed by flushing
      the sensing plate by purified air. While we found that the removal of the
      developed color can be accelerated by simultaneous heating and suction,
      permitting the reuse of the same sensing area multiple times, we also observed
      that the sensitivity gradually decreased. The nitrosonium calixarene derivative
      tends to transform to the nitrated form; this process is catalyzed by light.
      Several methylated calixarenes were synthesized and tested but a fully
      satisfactory solution has proven elusive.

PMID- 19159805
TI  - Determination of soluble ions and elements in ambient air suspended particulate
      matter: Inter-technique comparison of XRF, IC and ICP for sample-by-sample
      quality control.
AB  - In this paper, we describe a validation procedure for chemical fractionation
      analysis of elements (Al, As, Ba, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, S,
      Sb, Si, Sr, Ti and V) and soluble ions (Cl(-), NO(3)(-), SO(4)(2-), Na(+),
      NH(4)(+), Mg(2+), Ca(2+)) in suspended particulate matter (PM). The procedure
      applies three distinct measurement techniques (XRF, IC and ICP-OES) to the
      analysis of individual samples. The techniques used generate different outputs at
      different stages in the procedure. This makes it possible to identify the
      contributions of specific parameters to measurement uncertainty. On this basis,
      we propose a scheme for controlling the analytical quality of data from
      individual samples in which inter-technique comparisons is used in the same way
      many analytical methods use surrogates. We apply this scheme to about 310 samples
      of PM(10) and PM(2.5) identifying and assessing the main factors contributing to
      measurement uncertainty. This procedure successfully resolved a number of
      difficulties frequently encountered during the analysis of PM, including lack of
      appropriate reference materials and the low reliability of alternative techniques
      of quality control. The results demonstrate the critical importance of sample
      treatment prior to destructive analysis by IC and ICP.

PMID- 19159806
TI  - Evaluation of the arsenic binding capacity of plant proteins under conditions of
      protein extraction for gel electrophoretic analysis.
AB  - As prerequisite for the investigation of arsenic-binding proteins in plants, the
      general influence of different extraction parameters on the binding behaviour of
      arsenic to the plant protein pool was investigated. The concentration of the
      extraction buffer affected the extraction yield both for proteins and for arsenic
      revealing an optimal buffer concentration of 5mM Tris/HCl, pH 8. The addition of
      1 or 2% (w/v) SDS to the extraction buffer produced a two- to threefold
      enhancement of the total protein extraction yield but strongly suppressed the
      simultaneous extraction of arsenic from 80+/-8% extraction yield obtained without
      SDS to 48+/-2% in presence of 2% (w/v) SDS. The arsenic binding capacity of the
      protein fraction obtained after extraction with Tris buffer and protein
      precipitation by trichloroacetic acid in acetone was estimated to be 1.4+/-0.6%
      independently on the original spiking concentration of arsenic provided in the
      form of monomethylarsonate to the extracts. Due to the low total protein
      concentrations of the plant extracts that varied in the range from 75 to 412
      microgmL(-1) depending on the extraction parameters, high arsenic concentrations
      of 263-1001 mg (kgproteinmass)(-1) resulted for spiking concentrations of 10
      mgAsL(-1). The optimized protein isolation procedure was applied to plants grown
      under arsenic exposure and revealed a similar arsenic binding capacity as for the
      spiked protein extracts.

PMID- 19159807
TI  - Bioaerosols chemometric characterization by laser-induced fluorescence: air
      sample analysis.
AB  - A laser-induced fluorescence (LIF) system was optimized using a solution of
      Micrococcus luteus in ethanol/water 50% (v/v) to obtain spectra in the gas phase
      of 46 bioaerosols. Experimental designs such as Plackett-Burman and factorial
      design were applied. The fluorescence spectra were treated chemometrically by
      principal component analysis, linear discriminant analysis and hierarchical
      cluster analysis to classify the microorganisms according to family, morphology
      and gram. The best results were obtained using LDA. The method was applied to air
      samples and the LIF results allowed to characterize bioaerosols reliability. The
      robustness of the technique was demonstrated by the identification of many
      bacteria.

PMID- 19159808
TI  - Lipoic acid-palladium complex interaction with DNA, voltammetric and AFM
      characterization.
AB  - The mechanism of interaction of lipoic acid-palladium complex (LAPd) with double
      stranded DNA (dsDNA), as well as the adsorption process and the redox behaviour
      of LAPd, of its ligand lipoic acid (LA), and of the LAPd-containing dietary
      supplement, Poly-MVA, were studied using atomic force microscopy (AFM) and
      voltammetry at highly oriented pyrolytic graphite (HOPG) and glassy carbon
      electrodes. In the presence of small concentrations of LAPd molecules, the dsDNA
      molecules appeared less knotted and bended, and more extended on the HOPG
      surface, when compared with the dsDNA molecules adsorbed from the same dsDNA
      solution concentration. The voltammetric results demonstrated the interaction of
      both LAPd and Poly-MVA with dsDNA, but no oxidative damage caused to dsDNA was
      detected. AFM images revealed different adsorption patterns and degree of surface
      coverage and correlation with the structure, the concentration of the solution,
      the applied potential, and the voltammetric behaviour of the LA, LAPd and Poly
      MVA was observed. The application of a negative potential caused the dissociation
      of the LAPd complex and Pd(0) nanoparticle deposition, whereas the application of
      a positive potential induced the oxidation of the LAPd complex and the formation
      of a mixed layer of LA and palladium oxides.

PMID- 19159809
TI  - Dispersive liquid-liquid microextraction preconcentration of palladium in water
      samples and determination by graphite furnace atomic absorption spectrometry.
AB  - A new method for the determination of palladium was developed by dispersive
      liquid-liquid microextraction preconcentration and graphite furnace atomic
      absorption spectrometry detection. In the proposed approach,
      diethyldithiocarbamate (DDTC) was used as a chelating agent, and carbon
      tetrachloride and ethanol were selected as extraction and dispersive solvent.
      Some factors influencing the extraction efficiency of palladium and its
      subsequent determination, including extraction and dispersive solvent type and
      volume, pH of sample solution, concentration of the chelating agent and
      extraction time, were studied and optimized. Under the optimum conditions, the
      enrichment factor of this method for palladium reached at 156. The detection
      limit for palladium was 2.4ngL(-1) (3sigma), and the relative standard deviation
      (R.S.D.) was 4.3% (n=7, c=1.0ngmL(-1)). The method was successfully applied to
      the determination of trace amount of palladium in water samples.

PMID- 19159810
TI  - Glutathione-capped CdTe quantum dots for the sensitive detection of glucose.
AB  - A simple and sensitive assay system for glucose based on the glutathione (GSH)
      capped CdTe quantum dots (QDs) was developed. GSH-capped CdTe QDs exhibit higher
      sensitivity to H(2)O(2) produced from the glucose oxidase catalyzed oxidation of
      glucose, and are also more biocompatible than other thiols-capped QDs. Based on
      the quenching of H(2)O(2) on GSH-capped QDs, glucose can be detected. The
      detection conditions containing reaction time, the concentration of glucose
      oxidase and the sizes of QDs were optimized and the detection limits for glucose
      was determined to be 0.1 microM; two detection ranges of glucose from 1.0 microM
      to 0.5mM and from 1.0 mM to 20 mM, respectively were obtained. The detection
      limit was almost a 1000 times lower than other QDs-based optical glucose sensing
      systems. The developed glucose detection system was simple and facile with no
      need of complicated enzyme immobilization and modification of QDs.

PMID- 19159811
TI  - Thermo-reversibility of the fluorescence enhancement of acridine orange induced
      by supramolecular self-assembly.
AB  - Fluorescence enhancement of acridine orange (AO) in supramolecular hydrogels
      formed by self-assembly of the gelators 3-{[(2R)-2-(octadecylamino)-3
      phenylpropanoyl]amino}butyrate (TC(18)PheBu) and 1,3:2,4-di-O-benzylidene-d
      sorbitol (DBS) was investigated by steady-state and varying temperature
      fluorescence, polarized fluorescence and time-resolved fluorescence techniques.
      The results showed that the fluorescence intensities of AO in the gels remarkably
      increased in comparison with AO aqueous solutions, and increased with an increase
      of the gelator concentrations. The varying temperature fluorescence analysis
      indicated that fluorescence intensities of AO in the gels decreased upon an
      increase of temperature, and vice versa. This can be attributed to aggregation
      and dissociation of the gelators in the systems, since the fluorescence
      enhancement of AO was induced by self-assembly of the gelators. Polarized
      fluorescence analysis indicated that the values of anisotropy (r) of AO are
      significantly higher than that in water. This further confirmed that the three
      dimensional network formed by the gelator aggregates constrained the rotation of
      AO entrapped within the gels, resulting in high values of anisotropy. Time
      resolved fluorescence analysis indicated that the rates of fluorescence decay in
      the gels are lower than that in water. These results reveal thermo-reversibility
      of the fluorescence enhancement of AO in supramolecular hydrogels.

PMID- 19159812
TI  - Development and validation of LC methods with visible detection using pre-column
      derivatization and mass detection for the assay of voglibose.
AB  - Two sensitive and selective liquid chromatographic methods were developed for the
      assay of voglibose (VB) and validated as per International Conference on
      Harmonization (ICH) guidelines. First method is based on the pre-column
      derivatization of VB followed by visible detection (LC-VD) and second method
      involves mass spectrometric detection (LC-MS). In LC-VD method, VB was
      derivatized with sodium metaperiodate and 3-methyl-2-benzothiazolinone hydrazone
      hydrochloride monohydrate (MBTH). The derivatized color product of VB (DCPVB) was
      run through Novapak C18 (300 x 3.9 mm, 4 microm) column using the mobile phase
      containing buffer (0.01 M mixture of sodium di hydrogen orthophosphate and
      disodium hydrogen orthophosphate, pH 6.0) and acetonitrile in 35:65 v/v ratio.
      The eluted DCPVB was monitored at 667 nm. The fixation of optimum conditions in
      LC-VD method is described. DCPVB structure was confirmed by mass spectral
      analysis. In LC-MS method, VB was passed through Venusil XBPPH (150 x 4.6 mm, 5
      microm) column using a 95:5 v/v mixture of 0.01% formic acid and methanol as
      mobile phase. The assay concentrations of VB in pure form and in tablets for LC
      VD and LC-MS methods are 25 and 5 ngml(-1), respectively.

PMID- 19159813
TI  - Preliminary evaluation of monolithic column high-performance liquid
      chromatography with tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence detection
      for the determination of quetiapine in human body fluids.
AB  - High-performance liquid chromatography (HPLC) with tris(2,2'
      bipyridyl)ruthenium(II) chemiluminescence detection methodology is reported for
      the determination of the atypical antipsychotic drug quetiapine and the
      observation of its major active and inactive metabolites in human urine and
      serum. The method uses a monolithic chromatographic column allowing high flow
      rates of 3 mLmin(-1) enabling rapid quantification. Flow injection analysis (FIA)
      with tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence detection and HPLC time
      of flight mass spectrometry (TOF-MS) were used for the determination of
      quetiapine in a pharmaceutical preparation to establish its suitability as a
      calibration standard. The limit of detection achieved with FIA was 2 x 10(-11)
      molL(-1) in simple aqueous solution. The limits of detection achieved with HPLC
      were 7 x 10(-8) and 2 x 10(-10) molL(-1) in urine and serum, respectively. The
      calibration range for FIA was between 5 x 10(-9) and 1 x 10(-6) molL(-1). The
      calibration ranges for HPLC were between 1 x 10(-7)-1 x 10(-4) and 1 x 10(-8)-1 x
      10(-4) molL(-1) in urine and serum, respectively. The quetiapine concentrations
      in patient samples were found to be 3 x 10(-6) molL(-1) in urine and 7 x 10(-7)
      molL(-1) in serum. Without the need for preconcentration, the HPLC detection
      limits compared favourably with those in previously published methodologies. The
      metabolites were identified using HPLC-TOF-MS.

PMID- 19159814
TI  - A sequential extraction procedure for an insight into selenium speciation in
      garlic.
AB  - A sequential extraction procedure was developed for the fractionation of
      different classes of selenium species present in garlic. The consecutive steps
      included leaching with water, extraction of cell-wall bound species after lysis
      with a mixture of cellulase, chitinase and beta-glucanase completed by a
      proteolytic attack, extraction with HCl to liberate the residual organic bound
      species and finally, extractions with sulfite solution and CS(2) to complete the
      mass balance by the recovery of Se(0) and Se(2-), respectively. Selenium
      speciation in the aqueous fractions was probed by anion-exchange and ion-pairing
      reversed-phase HPLC-ICP MS after purification by preparative size-exclusion LC.
      It was found to be strongly affected by the sample redox conditions. The peak
      identity was matched with a mixture of 9 compounds expected to be present in
      allium plants; electrospray QTOF MS turned out to be unsuccessful. Selenite,
      selenate and selenomethionine were the dominating species present.

PMID- 19159815
TI  - In this issue...

PMID- 19159817
TI  - Spinal cord glioblastoma multiforme of conus medullaris masquerading as high
      lumbar disk herniation.
AB  - BACKGROUND: A case of primary intramedullary glioblastoma occurring at conus
      medullaris is presented, which was initially undetected and misdiagnosed as L1
      through L2 disk herniation. CASE DESCRIPTION: After the performance of L1 through
      L2 discectomy, the patient's initial painful symptom did not subside. The patient
      then developed a progressive paraparesis. The outside surgeons only predicted the
      possibility of reherniation or hematoma collection at the former operated level
      as the diagnosis for the paraparesis. After the patient was transferred to our
      hospital and after a thorough review of initial and follow-up magnetic resonance
      imaging with enhancement before second operation, an enlarged conus medullaris
      with mixed signal intensity was noted without evidence of re-herniation or
      hematoma collection. The patient underwent reoperation with biopsy of the
      intramedullary lesion, which was histologically confirmed as primary
      glioblastoma. CONCLUSION: Careful neurologic and radiologic evaluations should
      precede before any decision of surgical intervention as intramedullary and
      degenerative pathologies may coexist in the upper lumbar spine.

PMID- 19159819
TI  - "If you do not take control of your life, someone else will".

PMID- 19159822
TI  - Allergen-driven suppression of thiol production by human dendritic cells and the
      effect of thiols on T cell function.
AB  - Dendritic cells are a major source of extracellular thiols needed for T cell
      activation, a process in which CD40-mediated stimulation plays a pivotal role.
      The Dermatophagoides pteronyssinus group 1 mite allergen (Der p 1) has previously
      been shown to cleave CD40 from the surface of human dendritic cells, thereby
      suggesting that Der p 1 might compromise the ability of these cells to sustain
      thiol production during T cell activation. This has therefore prompted us to
      examine the effect of the mite protease allergen Der p 1 on thiol production by
      human dendritic cells. Monocyte-derived dendritic cells were treated with either
      proteolytically active or inactive Der p 1 and then stimulated through CD40 for
      extracellular thiol detection. The effect of thiol (N-acetyl-l-cysteine) and
      thiol inhibitors on naive T cell responses, including CD25 and FOXP3 expressions,
      cell proliferation and cytokine production, was determined. Here, we show that
      Der p 1-mediated cleavage of CD40 from the surface of dendritic cells suppresses
      the ability of these cells to produce extracellular thiols, and that reducing
      thiols are needed for the generation of the T helper type 1 (Th1), T cytotoxic
      type 1 (Tc1) and T regulatory (Treg) cell phenotypes. We conclude that Der p 1
      driven suppression of thiol production by dendritic cells may disrupt Th1/Tc1 and
      Treg cell development, and in doing so could lead to Th2/Tc2 cell responses and
      allergy.

PMID- 19159823
TI  - The pharmacodynamic effect of sirolimus: individual variation of cytokine mRNA
      expression profiles in human whole blood samples.
AB  - Sirolimus (SRL) has become an important alternative to calcineurin inhibitors due
      to its unique mechanism of action. Since rejection and poor graft outcome are
      still frequent problems despite therapeutic-range blood concentrations,
      pharmacodynamic measurements of its immunosuppressive effects would be of great
      clinical value to optimize treatment in individual patients. We performed a human
      whole blood assay using real time cytokine RT-PCR for the pharmacodynamic
      assessment of SRL. IL-2, IL-4 and IL-6 mRNA levels were quantitatively determined
      upon T-cell-specific stimulation in healthy individuals (n=11; in vitro) and in
      kidney-transplant patients (n=3; ex vivo). Furthermore, IL-2 protein secretion
      and T-cell proliferation was measured. After 24h incubation we observed a
      stronger suppression of IL-2 and IL-4 mRNA expression upon SRL addition (p<0.005;
      p<0.005) versus 4h (p<0.05; p<0.05). SRL effects displayed a remarkable
      interindividual variation, which proved to be independent of the concentration
      applied. Notably, 3/11 and 2/11 individuals had unaffected IL-2 and IL-4 mRNA
      expression after 4h incubation with SRL, respectively. In contrast, a general
      suppression of IL-2 protein secretion and T-cell proliferation was induced.
      Analysis of kidney-transplant patients verified interindividual variation and
      proved comparability of in vitro and ex vivo effects. We describe an individual
      degree of SRL-sensitivity that may correlate with clinical efficacy. Rather than
      analysis of one single peak, we suggest determination of two absolute cytokine
      mRNA peak levels for the pharmacodynamic assessment of SRL. However, prospective
      clinical studies are necessary to determine whether individual degrees of SRL
      sensitivity correlate with clinical outcome.

PMID- 19159824
TI  - Aqueous extract of Rhodiola imbricata rhizome stimulates Toll-like receptor 4,
      granzyme-B and Th1 cytokines in vitro.
AB  - Rhodiola imbricata is a medicinal plant, native to mountainous regions of Asia,
      parts of Europe, and the Arctic. Traditionally it is recommended to help combat
      fatigue and restore energy. It exhibits anti-stress, anti-cancer, and
      immunostimulatory activities. However, the effect of Rhodiola on immunological
      responses largely remains unknown. In this study, we have investigated the effect
      of aqueous extract of R. imbricata rhizome (RAE), on Toll-like receptor-4 (TLR-4)
      and intracellular granzyme-B expression in mouse splenocytes. Furthermore,
      TH1/TH2 cytokine profile was analyzed in RAE-treated human peripheral blood
      mononuclear cells (PBMCs) using multiplex flowcytomix kit. Our findings suggest
      that RAE induces TLR-4 expression and intracellular granzyme-B in treated
      splenocytes while RAE stimulated IL-1beta, IL-6, and TNF-alpha in human PBMCs.
      The present study suggests that RAE stimulates the innate immune pathway and has
      potent immunostimulatory activity, which can be used in modulating the immune
      system of immunocompromised individuals.

PMID- 19159825
TI  - Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in
      murine water immersion stress model.
AB  - Chronic fatigue syndrome, infection and oxidative stress are interrelated in
      epidemiological case studies. However, data demonstrating scientific validation
      of epidemiological claims regarding effectiveness of nutritional supplements for
      chronic fatigue syndrome are lacking. This study is designed to evaluate the
      effect of natural polyphenol, curcumin, in a mouse model of immunologically
      induced fatigue, where purified lipopolysaccharide (LPS) and Brucella abortus
      (BA) antigens were used as immunogens. The assessment of chronic fatigue syndrome
      was based on chronic water-immersion stress test for 10 min daily for 19 days and
      the immobility time was taken as the marker of fatigue. Mice challenged with LPS
      or BA for 19 days showed significant increase in the immobility time and
      hyperalgesia on day 19, as well as marked increase in serum tumor necrosis factor
      alpha (TNF-alpha) levels. Concurrent treatment with curcumin resulted in
      significantly decreased immobility time as well as hyperalgesia. There was
      significant attenuation of oxidative stress as well as TNF-alpha levels. These
      findings strongly suggest that during immunological activation, there is
      significant increase in oxidative stress and curcumin can be a valuable option in
      the treatment of chronic fatigue syndrome.

PMID- 19159826
TI  - Expression of interleukin-21, interleukin-21 receptor alpha and related type I
      cytokines by intravascular graft leukocytes during acute renal allograft
      rejection.
AB  - Interleukin-21 (IL-21), a member of the type I cytokine family, regulates central
      functions of immunity. Within this family, signaling is mediated via a receptor
      complex consisting of a high-affinity receptor chain and the common gamma-chain
      (IL-2Rgamma, CD132). We analyze the mRNA expression of IL-21, IL-21 receptor
      alpha (IL-21Ralpha) and family members IL-15, IL-2Rgamma, IL-21Ralpha, IL
      15Ralpha, IL-2/15Rbeta, as well as IL-2Ralpha (CD25) in leukocytes isolated by
      vascular perfusion of rat renal allografts. Mononuclear leukocytes expressed
      increased amounts of IL-21Ralpha mRNA and protein during acute rejection. Most IL
      21Ralpha-positive cells were monocytes. Furthermore, IL-21 and IL-2Ralpha mRNA
      expression was strongly increased. No changes in IL-2Rgamma, IL-2/15Rbeta, IL-15,
      and IL-15Ralpha mRNA expression levels were seen. In conclusion, we demonstrate
      that IL-21Ralpha expression is induced in intravascular monocytes in vivo in
      response to allogeneic transplantation. The function of the IL-21/IL-21R system
      in monocytes and during acute allograft rejection remains to be established.

PMID- 19159827
TI  - Identification of critical antibody-binding sites in the HIV-1 gp41 six-helix
      bundle core as potential targets for HIV-1 fusion inhibitors.
AB  - Formation of the six-helix bundle (6-HB) core between the N- and C-terminal
      heptad repeats (NHR and CHR) regions of the HIV-1 envelope glycoprotein (Env)
      transmembrane subunit gp41 is a critical step during the process of virus and
      target cell membrane fusion. In the present study, we generated a panel of five
      monoclonal antibodies (mAbs) which specifically recognized the HIV-1 gp41 6-HB
      formed by the NHR-peptide N36 and CHR-peptide C34 mixture, but did not react with
      the isolated peptides N36 and C34. These mAbs did not block the HIV-1 Env
      mediated cell-cell fusion at physiological temperature (37 degrees C), but
      inhibited the HIV-1 Env-mediated cell-cell fusion at suboptimal temperature (31.5
      degrees C), under which condition the fusion process is slowed down and the viral
      6-HB becomes accessible. The fusion inhibitory activity of the mAbs is correlated
      with their binding affinity with the 6-HB core. By screening 24 6-HB variants
      with single mutations at the b, c, and f positions in the helical wheels, we
      found that the critical binding sites of these mAbs were localized in the N
      terminal region of the NHR and the C-terminal region of the CHR. These sites may
      serve as targets for design of small molecule HIV fusion inhibitors, e.g.,
      organic compounds, peptides, and low molecular weight proteins.

PMID- 19159828
TI  - Human embryo immune escape mechanisms rediscovered by the tumor.
AB  - Towards the end of the 1990s, the two opposing theories on immunosurveillance and
      immunostimulation were extensively studied by researchers in an attempt to
      understand the complex mechanisms that regulate the relation between tumors and
      the host's immune system. Both theories probably have elements that would help us
      to comprehend how the host can induce anti-tumor clinical responses through
      stimulation of the immune system and which could also give us a deeper insight
      into the mechanisms of tumor immunosuppression. The model that most resembles the
      behavior of tumor cells in terms of growth, infiltration and suppression of the
      immune system of the environment in which they live is undoubtedly that of the
      embryonic cell. The fetus behaves like an allogenic transplant within the
      mother's body, using every means it has to escape from and defend itself against
      the mother's immune system. The majority of these mechanisms are the same as
      those found in tumor cells: antigenic loss, lack of expression of classic HLA-I
      molecules, production of immunosuppressive cytokines, induction of lack of
      expression of co-stimulatory molecules in antigen presenting cells, and induction
      of apoptosis in infiltrating lymphocytes, with activation of a type Th2
      regulatory lymphocyte response. A careful and comparative study of key mechanisms
      capable of triggering tolerance or cytotoxicity in both embryonic and tumor cells
      could prove immensely valuable in designing new strategies for anti-tumor
      immunotherapy.

PMID- 19159829
TI  - Characterization of fucose-binding lectins in rock- and mud-dwelling snails
      inhabiting Kuwait Bay.
AB  - Two novel lectins that bind selectively to trematode-associated fucosylated
      determinants have been characterized and purified from the hemolymph of wild-type
      rock-dwelling Turbo coronatus and mud-dwelling Cerithidea cingulata snails
      inhabiting Kuwait Bay. Both lectins were separately purified from the hemolymph
      of T. coronatus (designated Tc lectin) and C. cingulata (designated Cc lectin) by
      affinity chromatography on immobilized L-fucose-agarose columns and elution with
      a gradient of 0.1-1 M L-fucose. Assessments of the structural characteristics, by
      one- and two-dimensional polyacrylamide gel electrophoresis, indicated that Tc
      and Cc lectins were structurally distinct, and exist in their native forms as
      multimers of non-covalently associated subunits of different sizes and pIs.
      Removal of N-linked glycans by endo-beta-N-acetylglucosaminidase F resolved the
      heterodisperse pattern of Tc lectin subunits into 31 and 27 kDa components (each
      with a pI of 7.8) as well as an 8 kDa component with a pI of 7.2, and collapsed
      the size microheterogeneity of the Cc lectin subunits into a single spot of 33
      kDa (pI 5.4). Each of these subunits is subjected to differential post
      translational N-linked glycosylations, which involve variable acidic complex-type
      units in Tc lectin and neutral high-mannose-type units in Cc lectin. Based on
      trematode glycoprotein binding and inhibition assays, the two lectins exhibited
      optimum binding at a similar pH range, but were distinct in terms of their
      temperature stability as well as binding affinities towards the fucose moiety
      constituting the fucosylated target.

PMID- 19159830
TI  - Introduction to the special series on child and adolescent mental health.

PMID- 19159831
TI  - Understanding disruptive behavior problems in preschool children.
AB  - Disruptive behavior problems in young children are the number one reason for
      referral to mental health agencies. However, owing to difficulties
      differentiating clinically significant disruptive behaviors from typical
      development, a significant proportion of young children with disruptive behavior
      problems go unidentified and untreated. Research supports the existence of
      disruptive behavior disorders in young children, and early identification and
      treatment are critical to interrupt the trajectory of early problems to more
      significant and impairing difficulties. The purposes of this article were to
      identify and discuss disruptive behavior problems in preschool children and to
      introduce readers to current definitions of disruptive behavior problems and
      emotion regulation. A review of risk factors and underlying emotion and behavior
      regulation difficulties implicated in the development of disruptive behavior
      problems is provided. Furthermore, clinical implications for nurses in the
      identification of disruptive behavior problems in preschool children for
      pediatric nurses are discussed.

PMID- 19159832
TI  - Mood disorders in children and adolescents.
AB  - Childhood mood disorders such as major depression, dysthymia, and bipolar
      disorder have been found to be highly prevalent among children and adolescents.
      The emotional and behavioral dysfunction associated with these mood disorders can
      cause impairments across areas of functioning, including academic and social
      arenas. This article reviews the course, possible causes, assessment, and
      treatment of this group of disorders in youth and concludes by examining the
      implications for nurses and other health care providers of youth with mood
      disorders.

PMID- 19159833
TI  - Anxiety disorders in youth.
AB  - Anxiety disorders are one of the most prevalent categories of childhood and
      adolescent psychopathology. Due to their distressing, time-consuming, and/or
      debilitating nature, impairments in academic, social, and family functioning are
      often substantial. This article reviews the nature, etiology, assessment, and
      treatment of anxiety disorders in youth. We conclude by reviewing implications
      for nurses involved in the care of youth with anxiety disorders.

PMID- 19159834
TI  - Caring for children with autism spectrum disorder. Part I: prevalence, etiology,
      and core features.
AB  - Autism spectrum disorder (ASD) affects 1 in 150 children and has been gaining
      national attention over the past decade. Given the prevalence of this disorder,
      there is a high probability that pediatric nurses will care for a child with ASD,
      regardless of the setting in which they work. Children with ASD traverse the
      primary care outpatient setting, schools, subspecialty clinics, and inpatient
      units. A basic understanding of the current issues regarding prevalence and
      etiology, coupled with knowledge of the core features of ASD, will help pediatric
      nurses in all settings and at various practice levels better care for these
      children.

PMID- 19159835
TI  - Caring for children with autism spectrum disorder. Part II: screening, diagnosis,
      and management.
AB  - Recent emphasis on the importance of early identification and intervention for
      children with autism spectrum disorder (ASD) highlights the need for nurses in
      the community and primary care settings to learn to screen for ASD in children.
      In addition, given that ASD now affects 1 in 150 children, it is probable that
      nurses in a variety of settings, at all practice levels, will encounter children
      with ASD. Nurses need to be able to support families, educate parents, manage
      basic issues relevant to ASD, and advocate for these children and their families.

PMID- 19159836
TI  - Prevention is best for fetal alcohol syndrome.

PMID- 19159837
TI  - Breast-feeding and lactational amenorrhea in the United Arab Emirates.
AB  - This study was designed to investigate the relation of breast-feeding and weaning
      practices with the duration of lactational amenorrhea among breast-feeding
      mothers in the United Arab Emirates. A total of 593 mothers were interviewed in
      the Maternal and Child Health Centers in three areas: Abu Dhabi, Dubai, and Al
      Ain. The total mean duration of lactational amenorrhea in this study was 6.1
      months, and there was a direct relation with the length of exclusive breast
      feeding. The duration of postpartum amenorrhea was the longest in Al Ain (7.2
      months), as compared with Dubai (6.9 months) and Abu Dhabi (4.3 months). The age
      of the infant when formula milk and solid supplements were introduced was
      significantly related to the duration of lactational amenorrhea. This study
      confirms the results of other studies concerning the effectiveness of the
      lactational amenorrhea method as a natural method of contraception for the first
      6 months postpartum, especially for mothers who breast-feed exclusively and more
      frequently and who delay the introduction of food supplements.

PMID- 19159838
TI  - Reducing premature osteoarthritis in the adolescent through appropriate
      screening.
AB  - Osteoarthritis affects all ages. The etiology of this debilitating disease is
      multifactorial; however, several genes are linked to osteoarthritis. Sports
      participation, injury to the joint, obesity, and genetic susceptibility
      predispose adolescent athletes to the development of premature osteoarthritis.
      Assessment for the risk of osteoarthritis includes obtaining a family history to
      detect any genetic predisposition, obtaining body weight and body mass index, and
      identifying the patient's exercise regime and sports participation. Strategies to
      prevent the development of osteoarthritis in the adolescent include patient
      education, exercises to build quadriceps strength, low-impact activities, and the
      maintenance of a healthy weight. The devastating effects of premature
      osteoarthritis can be reduced if an assessment for risk of the disease is
      performed during adolescence.

PMID- 19159839
TI  - Fracture of fully coated echelon femoral stems in revision total hip
      arthroplasty.
AB  - Three cases of fractured uncemented, fully porous Echelon femoral stems (Smith &
      Nephew, Memphis, Tenn) are examined. Fracture of these components, an uncommon
      complication of revision hip surgery, is thought to result from cantilever
      bending after distal bony ingrowth. The stems in these cases fractured at 11, 22,
      and 28 months after revision surgery. Risk factors include increased body weight,
      excessive activity, an undersized stem, varus alignment, inadequate proximal
      femoral bone stock, and metallurgic defects. Extraction can be difficult and is
      often accomplished with the use of multiple trephines or via tamping through a
      distal cortical window.

PMID- 19159840
TI  - Comments from the retiring editor.

PMID- 19159841
TI  - The year in cardiothoracic and vascular anesthesia: selected highlights from
      2008.
AB  - The 2008 highlights in cardiovascular and thoracic anesthesia include the
      ultimate departure of aprotinin from clinical practice. However, a new
      antihypertensive drug, clevidipine, was approved for perioperative control of
      hypertension. There were also advances in pharmacologic myocardial conditioning
      with agents such as cyclosporine, sodium nitroprusside, and levosimendan.
      Furthermore, ischemic preconditioning appears ready for testing in large clinical
      trials designed to improve ischemic outcomes after cardiac surgery. With regard
      to transfusion, a landmark study suggests that transfused red blood cells stored
      for >2 weeks may significantly worsen major outcome after cardiac surgery.
      Furthermore, a second study suggests that relative rather than absolute
      hemoglobin reduction significantly determines adverse outcomes after cardiac
      surgery. These studies may greatly affect future transfusion guidelines. Left
      sided valve replacement has been revolutionized by transcatheter technology,
      which progressed significantly in 2008. Important advances in percutaneous
      coronary intervention included drug-eluting bioabsorbable stents and further
      insights into the clinical consequences of platelet resistance. These 2008 themes
      represent a sampling of the total highlights for the year. Many of the advances
      not covered have been reviewed and discussed in the literature review sections of
      the Journal in 2008.

PMID- 19159842
TI  - Case 1--2009. Retrocardiac sponge-induced hemodynamic instability after cardiac
      surgery.

PMID- 19159843
TI  - Pro: fellowship training in intensive care is required.

PMID- 19159844
TI  - Con: fellowship training in intensive care is not required.

PMID- 19159845
TI  - Response to Gerstein regarding guidelines of antiplatelet therapy management.

PMID- 19159846
TI  - Cardiovascular Revascularization Medicine 10-year anniversary.

PMID- 19159847
TI  - Summary of 'Hot Line' sessions presented at the European Society of Cardiology
      Congress 2008: August 30, 2008 to September 3, 2008, Munich, Germany.

PMID- 19159848
TI  - Comparison of bare metal stent with pioglitazone versus sirolimus-eluting stent
      for percutaneous coronary intervention in patients with Type 2 diabetes mellitus.
AB  - BACKGROUND: Drug-eluting stents (DESs) have been shown to decrease restenosis as
      compared with bare-metal stents. Recently, thiazolidinediones effectively reduced
      restenosis and the risk of repeat target vessel revascularization. We conducted a
      study to compare the performance of a DES with that of a bare-metal stent with
      pioglitazone in patients with Type 2 diabetes mellitus (DM). METHODS: The study
      was a prospective cohort trial involving 38 Type 2 diabetic patients referred for
      coronary stenting who were assigned to either the sirolimus-eluting stent (SES)
      group or the pioglitazone group. Quantitative coronary angiography was performed
      at study entry and at 6 months of follow-up to evaluate in-stent late luminal
      loss and the percentage of the luminal diameter and the rate of restenosis. We
      also analyzed major adverse cardiac events (MACE) at 12 months. RESULTS: There
      were no significant differences in glycemic control levels or in lipid levels in
      the two groups at follow up. The insulin and homeostasis model assessment insulin
      resistance at follow-up were significantly lower in the pioglitazone group than
      in the SES group. The percentage of restenosis was similar between the SES group
      and the pioglitazone group. The incidence of MACE at 1 year tended to be lower in
      the pioglitazone group than in the SES group. CONCLUSIONS: The bare-metal stent
      with pioglitazone is not inferior to the SES in the present study and is one of
      therapeutic strategies of percutaneous coronary intervention for patients with
      DM.

PMID- 19159849
TI  - Off-pump coronary artery bypass grafting improves in-hospital mortality in
      patients with dialysis-dependent renal failure.
AB  - OBJECTIVE: Patients with chronic dialysis-dependent end-stage renal disease are
      increasingly referred for coronary artery bypass grafting (CABG) and their early
      outcome is less favorable. Off-pump CABG (OPCAB) has achieved encouraging results
      in high-risk patients. Therefore, we designed this retrospective study to test
      the hypothesis that OPCAB reduced surgical risks in dialysis patients. METHODS:
      From January 2000 to December 2005, 294 dialysis-dependent patients received
      isolated CABG at the Washington Hospital Center. Among them, 168 underwent OPCAB
      (off-pump group), and 126, CABG with cardiopulmonary bypass (CPB) (on-pump
      group). The in-hospital outcomes were analyzed. RESULTS: The two groups were
      comparable in terms of preoperative characteristics. The Parsonnet's Bedside
      Score of the off-pump group was similar to that of the on-pump group (32.0 vs.
      32.0, P=.57). The in-hospital mortality of the off-pump group was significantly
      lower than that of the on-pump group (5.4% vs. 11.9%, P=.04). Although the
      percentage of patients who received transfusions was similar, the on-pump group
      received more total transfusions. Logistic regression analysis revealed that use
      of CPB independently predicted in-hospital mortality [odds ratio (OR), 5.0; 95%
      confidence interval, 1.78-13.85; P<.01] and perioperative myocardial infarction
      (MI; OR, 5.1; 95% confidence interval, 1.18-22.40; P=.03). No significant
      difference in long-term survival at 4 years was absorbed between the two groups
      of hospital survivors. CONCLUSIONS: Our data suggest that OPCAB is a safe
      alternative to on-pump CABG in dialysis patients. Avoiding CPB resulted in less
      perioperative blood utilization, MI, and hospital mortality.

PMID- 19159850
TI  - Metal allergic reaction in chronic refractory in-stent restenosis.
AB  - OBJECTIVES: This study examined the relationship between chronic refractory (CR)
      in-stent restenosis (ISR) and metal allergic reaction. BACKGROUND: Although drug
      eluting stent reduced the restenotic event compared with bare-metal stent, the
      mechanism of neointimal proliferation is not clear yet; however, bare-metal stent
      still remains as one of the choices. METHODS: Of 128 bare-metal stent implanted
      patients who experienced target lesion revascularization at least once, 60
      patients with the second ISR (study group) and 68 patients without the second ISR
      (control group) were compared in terms of result from the skin patch test for
      metal allergic reaction. RESULTS: Nickel was dominant among components of 316L
      stainless steel. The nickel-positive was observed in 19% (24/128) of all
      patients. Of 24 nickel-positive, 18 (30%) was in the study group, whereas 6 (9%)
      was in the control group (P=.02). According to multivariate analysis, the most
      significant predictor for CR-ISR was reference vessel diameter (P=.0010) followed
      by nickel-positive (P=.0033) and hyperlipidemia (P=.0305). The nickel-positive
      showed the highest odds ratio of 5.41 adjusted with confounder variables.
      CONCLUSION: This study with the second ISR showed that nickel was a major factor
      for CR-ISR. Further improvement of biocompatible material is required for
      coronary stents and strut-coating materials even in the drug-eluting stent era.

PMID- 19159851
TI  - Frequency and predictors of renal artery stenosis in patients with coronary
      artery disease.
AB  - BACKGROUND: Renal artery stenosis (RAS) remains underdiagnosed because of
      nonspecific clinical manifestations, including in patients with coronary artery
      disease (CAD). AIMS: To estimate the prevalence and identify predictors of RAS in
      patients with CAD undergoing coronary angiography. SETTING: University-based
      medical centre. METHODS: We enrolled 650 consecutive patients (mean age=67+/-10
      years, 80% men) with confirmed CAD. All patients underwent selective renal
      arteriography in the same procedure. We estimated the prevalence of RAS, defined
      as a >50% lesion. Multiple variable analysis of factors associated with presence
      of RAS was carried out using a logistic regression model. Variables that emerged
      as predictors by single-variable analysis were included in the model, along with
      variables that were tentatively associated with RAS, based on a literature
      review. RESULTS: RAS was detected in 94 patients (14.5%, 95% CI: 11.8-17.2%),
      including 20 (3.1%) with bilateral lesions. By single-variable analysis and
      presence and number of coronary artery stenoses (P<.001), hypertension (P=.001),
      and creatinine clearance <90 ml/min (P<.001) were associated with an increased
      risk of RAS. By multiple variable analysis, male sex (P<.05), presence and number
      of coronary artery lesions (P<.01), hypertension (P=.001), and renal
      insufficiency (P<.001) predicted the presence of RAS. CONCLUSIONS: The main
      clinical predictors of RAS in patients with CAD were hypertension, renal
      insufficiency, and multivessel CAD. These observations might help defining a high
      risk subgroup of patients in need of meticulous investigations of both CAD and
      RAS.

PMID- 19159852
TI  - The predictive value of computed tomography calcium scores: a comparison with
      quantitative volumetric intravascular ultrasound.
AB  - OBJECTIVE: To evaluate the relationship between coronary artery calcium scoring
      (CACS) and intravascular ultrasound (IVUS) calcification and disease severity.
      METHODS: Forty-five angina patients who underwent CACS 18+/-23 days before IVUS
      were studied. The CACS was recorded for each lesion matched to a specific IVUS
      lesion. Cross-sectional area measurements of the external elastic membrane, lumen
      area, plaque and media, and plaque burden were performed. The arc and length of
      calcification were measured. RESULTS: There were 106 calcified lesions detected
      by IVUS. Eighty-five of those lesions (80%) were detected by CACS, but 21
      calcified lesions (20%) were missed. Fourteen (50%) out of 28 of the lesions with
      an IVUS-calcium arc below the 25th percentile (51.4 degrees ) were detected by
      CACS vs. 91% of lesions with an IVUS-calcium arc >51.4 degrees (P<.05).
      Similarly, 21 (58%) of 36 lesions <or=3 mm in length were detected vs. 91% of
      lesions >3 mm (P<.05). We divided IVUS-calcified lesions into CACS <or=10 and
      >10. Mean plaque burden, calcified length, and arc of calcium increased
      significantly, while minimum lumen area decreased with increasing CACS. There was
      the same tendency in culprit and nonculprit calcified lesions, respectively.
      Multivariate analysis showed a calcified length (regression coefficient=8.718,
      95% CI 4.668-12.77, P<.001) and an arc of calcium (regression coefficient=2.789,
      95% CI 1.419-4.119, P<.001) were significant predictors for CACS. CONCLUSIONS:
      This study suggests that a CACS could evaluate coronary calcium burden
      noninvasively through the accurate estimation of calcium-arc and length.

PMID- 19159853
TI  - Risk and management of upper gastrointestinal bleeding associated with prolonged
      dual-antiplatelet therapy after percutaneous coronary intervention.
AB  - Prolonged dual-antiplatelet therapy with aspirin and clopidogrel is mandatory
      after drug-eluting stent implantation because of the potential increased risk of
      late stent thrombosis. The concern regarding prolonged antiplatelet therapy is
      the increased risk of bleeding. Gastrointestinal bleeding is the most common site
      of bleeding and presents a serious threat to patients due to the competing risks
      of gastrointestinal hemorrhage and stent thrombosis. Currently, there are no
      guidelines and little evidence on how best to manage these patients who are at
      high risk of morbidity and mortality from both the bleeding itself and the
      consequences of achieving optimum hemostasis by interruption of antiplatelet
      therapy. Managing gastrointestinal bleeding in a patient who has undergone recent
      percutaneous coronary intervention requires balancing the risk of stent
      thrombosis against further catastrophic bleeding. Close combined management
      between gastroenterologist and cardiologist is advocated to optimize patient
      outcomes.

PMID- 19159854
TI  - Computerized gradual balloon inflation: a novel strategy of coronary angioplasty
      superior to a standard manual approach.
AB  - BACKGROUND: Mechanical trauma caused by PCI is a primary reason for restenosis
      and subsequent target lesion revascularization (TLR). To minimize this trauma, we
      developed a computerized angioplasty pressure sensor and inflator device (CAPSID)
      for gradual inflation. The objective of this prospective randomized study was to
      examine whether use of CAPSID reduces early and late cardiac events in patients
      undergoing PCI. METHODS: Patients undergoing PCI were eligible and randomized to
      CAPSID or standard balloon inflation (plain old balloon angioplasty). In the
      CAPSID group, a slow, gradual balloon inflation was performed by a personal
      computer. Stenting was used in both groups only for suboptimal results. Patients
      with total occlusions and vein grafts were excluded. Clinical follow-up for major
      adverse cardiac events (MACE) was performed at 6 and 12 months, with repeat
      coronary angiography performed for clinical symptoms or positive stress testing.
      RESULTS: A total of 234 patients completed the study. At 1-year follow-up, the
      CAPSID group had a significantly lower rate of MACE (21% vs. 37%, P<.005). In
      patients who underwent angiography, there was a significantly lower rate of
      restenosis in the CAPSID group (20.2% vs. 35.5%). The reduction in TLR was even
      more pronounced in the subgroup undergoing stenting (8% vs. 24%; P<.001).
      CONCLUSIONS: We conclude that gradual computerized balloon inflation is more
      effective than standard manual balloon inflation in reducing adverse coronary
      events. The combination of CAPSID and subsequent stent deployment was especially
      effective in reducing TLR.

PMID- 19159855
TI  - Myocardium selective densitometric perfusion assessment after acute myocardial
      infarction.
AB  - BACKGROUND: Myocardial perfusion is an important prognostic factor after
      recanalisation in acute myocardial infarction patients. We present a
      computerized, densitometric measurement method to assess myocardial perfusion on
      phase-matched digitally subtracted coronary angiograms. METHODS AND MATERIALS:
      Quantitative myocardial perfusion was assessed by the G(max)/T(max) parameter of
      the time-density curves (TDCs) in infarct-related myocardial regions on X-ray
      coronary angiograms. Arteries were masked out from regions of measurement. This
      novel method has been compared with enzymatic infarct size, ST-segment
      resolution, and ejection fraction after successful revascularization of 62
      patients with acute myocardial infarction. RESULTS: Significant correlations were
      found between G(max)/T(max) and enzymatic infarct size (R=-0.445, P<.001), ST
      segment resolution (R=0.364, P=.004), and ejection fraction (R=0.278, P=.029).
      Bland and Altman plot of G(max)/T(max) reveals good interobserver agreement.
      CONCLUSIONS: G(max)/T(max) of the TDC measured in the infarct-related myocardial
      area is a reliable parameter to assess clinical indicators of myocardial
      reperfusion. Therefore, results suggest that it could be used to immediately
      assess the success of recanalisation at the tissue perfusion level during
      coronary intervention, and as an objective end point in clinical trials of new
      interventional devices and drugs.

PMID- 19159856
TI  - Extremely late drug-eluting stent thrombosis: 2037 days after deployment.
AB  - Thrombosis of drug eluting stents has been documented up to four years after
      stent implantation, often in the setting of cessation of antiplatelet therapy. We
      present a case of drug-eluting stent thrombosis, 2037 days after initial
      implantation, which we believe is the latest reported case. Late stent thrombosis
      remains a rare but catastrophic complication of coronary intervention. We
      hypothesize that the procoagulant milieu of surgery, coupled with cessation of
      one or both antiplatelet agents preoperatively, compounds the risk of
      perioperative stent thrombosis.

PMID- 19159857
TI  - Bare metal stent thrombosis 13 years after implantation.
AB  - There has been a great deal of recent controversy regarding the risk of very late
      stent thrombosis with drug eluting stents, especially in the context of
      antiplatelet therapy cessation. We report a case of very late stent thrombosis of
      a bare metal stent initially implanted for treatment of a myocardial infarction.
      The patient presented thirteen years later with a recurrent myocardial infarction
      three days after discontinuing aspirin. Angiography demonstrated thrombotic
      occlusion and severe underlying restenosis of the stent. To our knowledge, this
      is the latest bare metal stent thrombosis described in the world medical
      literature.

PMID- 19159858
TI  - Unusual cause of wide complex tachycardia during coronary angiography.
AB  - We present a case of wide-complex tachycardia occurring during coronary
      angiography in a patient with a dual chamber pacemaker. This rhythm recurred only
      during coronary injection of contrast and appeared to be ventricular tachycardia.
      However, subsequent examination revealed the development of fusion beats followed
      by fully paced ventricular beats during coronary injection, which only mimicked a
      potentially dangerous arrhythmia.

PMID- 19159859
TI  - Superselective embolization of renal hemorrhage occurring after percutaneous
      coronary intervention.
AB  - A 69-year-old female was hospitalized for acute coronary syndrome and received
      full antiplatelet and anticoagulant therapy. The patient underwent angioplasty
      and stent implantation on right coronary and left circumflex arteries with good
      angiographic result. After the procedure, the patient developed hemorrhagic shock
      due to massive left renal hemorrhage. An emergent digital subtraction angiography
      showed bleeding from a left segmental renal artery. The hemorrhage was
      successfully managed with transcatheter superselective embolization. The patient
      was discharged after 22 days in good general condition with normal renal
      function. One-year follow-up was uneventful.

PMID- 19159860
TI  - Subendomyocardial perfusion abnormality and necrosis detected by magnetic
      resonance imaging in a patient with isolated noncompaction of the ventricular
      myocardium associated with ventricular tachycardia.
AB  - A 74-year-old man presented with left ventricular failure and nonsustained
      ventricular tachycardia. Coronary angiography revealed normal coronary arteries;
      left ventriculography showed hypokinesis of the lateral wall segment. The
      ejection fraction was 54%. Cine-magnetic resonance imaging showed a double
      layered appearance on four-chamber view and marked trabeculations as well as
      intratrabecular recesses in the inferolateral segments on short-axis view,
      findings consistent with isolated noncompaction of the ventricular myocardium
      (INVM). Contrast-enhanced imaging revealed hypoperfusion and delayed enhancement
      of the endomyocardium in the inferolateral segments. Subendomyocardial perfusion
      abnormality and necrosis may constitute the diagnostic criteria of INVM.

PMID- 19159861
TI  - Females excel at basic face perception.
AB  - Females are generally better than males at recognizing facial emotions. However,
      it is not entirely clear whether and in what way females may also excel at non
      affective face recognition. Here, we tested males and females on two perceptual
      face recognition tasks that involved only neutral expressions: detection and
      identity discrimination. On face detection (Experiment 1), females were
      significantly more accurate than males in detecting upright faces. This gender
      difference was reduced during inverted face detection, and not present during
      tree detection, suggesting that the magnitude of the gender difference for
      performance co-varies with the extent to which face processing mechanisms are
      involved. On facial identity discrimination (Experiment 2), females again
      outperformed males, particularly when face images were masked by visual noise, or
      the delay between comparison face images was extended from 0.5 to 3s. These
      results reveal a female advantage in processing face-specific information and
      underscore the role of perceptual factors in socially relevant gender
      differences.

PMID- 19159862
TI  - Posterior vitreomacular adhesion and risk of exudative age-related macular
      degeneration: paired eye study.
AB  - PURPOSE: To evaluate posterior vitreomacular adhesion as a risk factor for
      choroidal neovascularization (CNV) in age-related macular degeneration (AMD).
      DESIGN: Retrospective, observational case series. METHODS: We retrospectively
      reviewed optical coherence tomography (OCT) and fluorescein angiography (FA) of
      251 consecutive patients with unilateral exudative AMD. Fellow eyes had no sign
      of exudative AMD. Vitreomacular adhesion was defined when posterior hyaloid line
      attached to inner retinal surface was seen in OCT. We compared the incidence of
      posterior vitreomacular adhesion between the 2 eyes and the association between
      CNV location and vitreomacular adhesion. RESULTS: We found posterior
      vitreomacular adhesion in 56 patients (22.3%), and 3 cases in which it was
      present in both eyes. CNV was mostly present in eyes with vitreomacular adhesion
      (44/53, 83%), and rarely found in eyes without vitreomacular adhesion (6/53,
      11.3%; P = .0007). The location of vitreomacular adhesion was always observed
      over the area of the CNV in exudative eyes (50/50). CONCLUSIONS: Posterior
      vitreomacular adhesion is associated with CNV in AMD. Chronic vitreomacular
      traction may be a risk factor for the development of exudative AMD.

PMID- 19159863
TI  - Concentration and fate of histatins and acidic proline-rich proteins in the oral
      environment.
AB  - Saliva plays a critical role in the protection of oral hard and soft tissues and
      contains a multitude of constituents with well-characterized biological
      activities in vitro. Among these are histatins and acidic proline-rich proteins
      (PRPs). Nevertheless, few functional studies have recognized the structural
      instability of these proteins in the proteolytic environment of whole saliva. The
      aim of this investigation was to determine histatin and acidic PRP levels in
      parotid secretion (PS) and in whole saliva (WS) as well as to establish their
      susceptibility to proteolysis in these salivary fluids. Using cationic
      polyacrylamide gel electrophoresis and densitometric analysis the average total
      histatin concentration (histatin 1+3+5) in WS was determined to be 33.3+/-16.7
      microg/ml (n=22) and the average total acidic PRP concentration (PRP1/PIF
      s+PRP3/PIF-f) was 427.9+/-123.3 microg/ml (n=22). Histatin and acidic PRP
      concentrations in PS were 6 and 1.5 times higher than in WS (n=7), respectively.
      WS histatin and acidic PRP levels each correlated significantly with WS total
      protein concentrations (P<0.01 and P<0.05, respectively), as well as with each
      other (P<0.01). Stability studies of histatin 3 and PRP1/Pif-s in PS revealed
      t(1/2) times of 7.2+/-5.5 and 50.3+/-24.8h, respectively (n=7). Histatin 3 (40
      microg/ml) and PRP1 (400 microg/ml), added to WS in concentrations equivalent to
      their concentrations in PS, disappeared at a much faster rate, with t(1/2) values
      of 1.7+/-1.6 min and 29.3+/-15.3 min, respectively (n=7). The data indicate that
      proteolysis in WS is an important factor in explaining the substantially lower
      concentrations of histatins and acidic PRPs in WS as compared to in glandular
      secretions.

PMID- 19159864
TI  - Evidence for the presence of carbonic anhydrase 29-kDa isoenzyme in salivary
      secretions of three ruminating species and the gelada baboon.
AB  - Salivary glands are highly variable in composition of their secretions and thus
      could be one of the primary ways by which species adapt or react to their
      environments. It has been hypothesized that feeding adaptation correlates with
      saliva composition. Hence, animals of different families using identical feeding
      niches should possess similar salivary proteins. For the first time, salivary
      secretions of grass-eating cattle, goat, camel and gelada baboon were compared by
      SDS-gel electrophoresis and immunoblotting. Salivary protein patterns were
      similar among individuals of the same species but varied largely among species.
      However, all samples showed proteins of apparently 29 and 42 kDa, identified as
      carbonic anhydrases (CA) by immunoblotting. The CA-VI (42 kDa) was highly
      expressed in cattle and camel saliva, but showed lower expression in goat saliva
      and could not be detected in gelada baboons. The CA-II (29 kDa) was found in
      saliva of all species tested and was shown in ruminating animals not to originate
      from cellular debris of the oral mucosa or ingested food. The results demonstrate
      that besides CA-VI, CA-II is another CA isoform secreted especially in ruminant
      saliva. Furthermore, the two CA isoenzymes detected may form a complementary
      system, protecting mucosa from acidity and helping to maintain a constant
      bicarbonate concentration in the animal's mouth and digestive tract.

PMID- 19159865
TI  - Schemas and Borderline Personality Disorder symptoms in incarcerated women.
AB  - There is increasing interest regarding the role of maladaptive cognition in
      Borderline Personality Disorder (BPD). The current study examined the
      relationship between early maladaptive schema (EMS) domains and BPD symptoms as
      well as whether schema domains account for the relationship between childhood
      maltreatment and BPD severity. Incarcerated women (N=105) were assessed for BPD
      symptoms via semi-structured diagnostic interview. Disconnection/Rejection and
      Impaired Limits were associated with BPD pathology although these domains shared
      variance with depression and antisocial personality disorder pathology,
      respectively. In addition, the relationship between childhood abuse and BPD
      severity was non-significant after controlling for schema domains. Related
      findings and the implications for cognitive treatment of BPD are discussed.

PMID- 19159866
TI  - Attentional bias for emotional faces in paediatric anxiety disorders: an
      investigation using the emotional Go/No Go task.
AB  - BACKGROUND: The present study examined contextual modulation of attentional
      control processes in paediatric anxiety disorders. METHOD: Anxious children
      (N=20) and non-anxious controls (N=20) completed an emotional Go/No Go task in
      which they responded on some trials (i.e., Go trials) when neutral faces were
      presented amongst either angry or happy faces to which children avoided
      responding (i.e., No Go trials) or when angry and happy faces were presented as
      Go trials and children avoided responding to neutral faces. RESULTS: Anxious
      girls were slower responding to neutral faces with embedded angry compared with
      happy face No Go trials whereas non-anxious girls were slower responding to
      neutral faces with embedded happy versus angry face No Go trials. Anxious and non
      anxious boys showed the same basic pattern as non-anxious girls. There were no
      significant group differences on No Go trials or when the emotional faces were
      presented as Go trials. CONCLUSIONS: Results are discussed in terms of selective
      interference by angry faces in the control of attention in anxious girls.

PMID- 19159867
TI  - The role of fear of anxiety and intolerance of uncertainty in worry: an
      experimental manipulation.
AB  - The tendency to fear emotional experiences, such as anxiety, may be an important
      factor in the maintenance of excessive worry, which is the central feature of
      generalized anxiety disorder (GAD). The goal of the present study was to clarify
      the role of fear of anxiety in worry by assessing whether the experimental
      manipulation of fear of anxiety affects worry level. The study also assessed the
      combined effects of fear of anxious responding and intolerance of uncertainty (a
      factor already linked to pathological worry) on level of worry by grouping
      participants according to their tolerance for uncertainty. The results indicated
      that participants whose fear of anxiety was increased showed higher levels of
      worry compared to participants whose fear of anxiety was decreased. This finding
      provides preliminary support for the causal role of fear of anxiety in worry.
      Moreover, the results showed that increased fear of anxiety in combination with
      an intolerance for uncertainty led to the highest levels of worry, which suggests
      that these constructs have an additive effect on worry. The findings lend support
      to the integration of new conceptualizations of psychopathology with existing
      models of excessive worry, which could ultimately increase treatment efficacy for
      GAD.

PMID- 19159868
TI  - Evidence of epistasis between the catechol-O-methyltransferase and aldehyde
      dehydrogenase 3B1 genes in paranoid schizophrenia.
AB  - BACKGROUND: Schizophrenia is a common yet severe psychiatric condition
      characterized by complex genetic mechanism and diverse clinical presentations.
      Our previous study indicated that the combined effect of two intronic single
      nucleotide polymorphisms (SNPs), which are located in the catechol-O
      methyltransferase (COMT) and aldehyde dehydrogenase 3B1 (ALDH3B1) genes,
      respectively, conferred genetic risk to paranoid schizophrenia. METHODS: To
      further explore the precise mechanism of the COMT and ALDH3B1 interaction
      involved in the pathophysiology of schizophrenia, we scanned all possible
      functional SNPs within these two genes by polymerase chain reaction (PCR)-based
      genotyping analysis in 540 paranoid schizophrenic patients and 660 control
      subjects from a Han Chinese population. We also determined the effects of
      schizophrenia-associated SNPs on the development of psychotic symptoms, P300
      event-related potential components induced by an auditory odd-ball task, and gene
      expression examined by quantitative real-time PCR analysis. RESULTS: The major
      findings of this study were that, among the individuals carrying the rs3751082 A
      allele in the ALDH3B1 gene, the rs4633 T allele in the COMT gene was associated
      with susceptibility to paranoid schizophrenia (p = .004), development of
      hallucination (p = 5.141 E-5), delay of P300 latency in both patients (p = .006)
      and control subjects (p = .02), and increased expression of the COMT gene in
      control subjects (p = .002). However, the rs4633 T allele did not show any
      association in the rs3751082 G/G genotype carriers. CONCLUSIONS: These findings
      provided convincing evidence that epistasis between the COMT and ALDH3B1 genes
      plays an important role in the pathogenesis of schizophrenia.

PMID- 19159869
TI  - Novel acylated lipo-oligosaccharides from the tubers of Ipomoea batatas.
AB  - Nine new lipo-oligosaccharides, batatosides H-P, were isolated from the tubers of
      Ipomoea batatas (Convolvulaceae). Spectral and chemical methods allowed to
      characterize them as tetra- or penta-saccharides that form a macrolactone with
      the aglycone, (11S)-hydroxyhexadecanoic acid (jalapinolic acid), the absolute
      configuration of which was established by Mosher's method. Batatosides L and O
      showed a weak inhibitory effect on the growth of Hep-2 cells, while the others
      proved to be inactive.

PMID- 19159870
TI  - Objective characterization of oesophageal voice supporting medical diagnosis,
      rehabilitation and monitoring.
AB  - Otolaryngologists use computational tools in the objective diagnosis of vocal
      folds pathologies by means of a set of acoustic parameters among others. This can
      be achieved in the cases of slight pathologies, but it does not exist any
      commercial software suitable for severe degradations of speech, as they are the
      oesophageal voice of laryngectomees. The present article shows a high-accuracy
      algorithm for the detection of the periodicity cycles of both oesophageal and
      laryngeal voices with low quality which allows the accurate and automatic
      estimation of pitch, jitter and shimmer. As the proposed algorithm works also
      with slighter pathologies, it is a useful contribution which allows doctors to
      perform an objective control during rehabilitation and monitoring stages. Thus, a
      patient can be controlled during oesophageal voice learning stage and it can also
      be saved a medical record with the results of the acoustic parameters'
      measurements in order to detect possible relapses.

PMID- 19159871
TI  - In vitro fertilization pregnancy in a patient with proven chronic endometritis.
AB  - OBJECTIVE: To report an in vitro fertilization (IVF) pregnancy in a patient with
      histologically confirmed chronic endometritis before the IVF treatment without
      prior antibiotherapy. DESIGN: Case report. SETTING: Academic reproductive
      medicine unit. PATIENT(S): A 30-year-old woman with primary infertility due to
      mild oligoasthenoteratospermia of the male partner. INTERVENTION(S): Diagnostic
      hysteroscopy and endometrial biopsy. MAIN OUTCOME MEASURE(S): Delivery after the
      first IVF. RESULT(S): Histologic examination of the endometrium revealed chronic
      endometritis. The patient delivered a healthy boy at 40 weeks' gestation after
      the first IVF treatment. CONCLUSION(S): Our findings suggest that the impact of
      chronic endometritis on infertility and IVF outcome should be further
      investigated in prospective randomized studies.

PMID- 19159872
TI  - Homologous in vitro fertilization in Turner syndrome: insights from a case
      report.
AB  - OBJECTIVE: To describe a bigeminal pregnancy obtained with a homologous
      intracytoplasmic sperm injection cycle in a patient with high-grade mosaic Turner
      syndrome (45,XO/47,XXX 97.5%/2.5%) with bicuspid aortic valve. DESIGN: Case
      report. SETTING: Unit of Pathophysiology of Human Reproduction in a general
      hospital. PATIENT(S): Patient with mosaic Turner syndrome with bicuspid aortic
      valve. INTERVENTION(S): Homologous intracytoplasmic sperm injection cycle after
      controlled ovarian hyperstimulation with a GnRH agonist flare-up depot protocol
      and menotropins. MAIN OUTCOME MEASURE(S): Pregnancy development,
      echocardiographic monitoring of aortic root, karyotypes of progeny. RESULT(S):
      Ongoing bigeminal pregnancy with the delivery of two healthy infants (46,XX and
      46,XY, respectively) by cesarean section without any cardiovascular complication
      or aortic root echocardiographic modification in the mother. CONCLUSION(S): Even
      in patients with Turner syndrome with high-grade 45,XO mosaicism and reduced
      ovarian reserve, a trial of homologous reproduction should be offered after a
      thorough cardiologic evaluation to avoid pregnancy-related cardiovascular
      complications.

PMID- 19159873
TI  - Emergency laparoscopy for suspected ovarian torsion: are we too hasty to operate?
AB  - OBJECTIVE: To reevaluate the rate of correct diagnosis of ovarian torsion (OT) in
      our department. DESIGN: Retrospective computerized chart review. SETTING:
      Tertiary referral center. PATIENT(S): Seventy-eight women who underwent
      laparoscopy for suspected OT. INTERVENTION(S): Laparoscopy. MAIN OUTCOME
      MEASURE(S): Rate of true diagnosis of torsion, correlation with Doppler studies.
      RESULT(S): The preoperative diagnosis of OT was confirmed in only 36 (46.1%) of
      the patients. Immediate operation (<10 hours) after admission (n = 48) was
      associated with a statistically significantly higher likelihood of operatively
      confirming OT (56.2% vs. 28.6%). We found that the lack of ovarian blood flow on
      Doppler sonography was a good predictor of OT; women with pathologic flow were
      statistically significantly more likely to have OT (77% vs. 29%). The sensitivity
      and specificity of abnormal ovarian flow for OT were 43.8% and 91.7%,
      respectively, with a positive and negative predictive value of 78% and 71%,
      respectively. CONCLUSION(S): Despite 20 years of research, the accuracy of the
      preoperative diagnosis of OT remains low. The urge to operate can be attributed
      to the importance of preserving ovarian function in young women as well as to the
      availability and the low associated complication rate of laparoscopy.

PMID- 19159874
TI  - Biogenesis of the sperm head perinuclear theca during human spermiogenesis.
AB  - We analyzed the appearance and localization of the sub-acrosomal perinuclear
      theca (PT) during human spermiogenesis. The PT is tightly associated with
      acrosomal biogenesis.

PMID- 19159875
TI  - Sex ratio is remarkably constant.
AB  - OBJECTIVE: To study whether the sex of the offspring is related to increasing
      parental age, gravidity, and parity, hypothesizing an altered male-to-female sex
      ratio with the advancing parental age. DESIGN: A large retrospective cohort
      study. SETTING: The study analyzed birth records of Hadassah Hebrew University
      Medical Center in Jerusalem from June 2003 to December 2006. PATIENT(S): 35,837
      birth records were analyzed including 941 multifetal deliveries, excluding
      foreign inhabitants (n = 744), missing data for the main study outcome (n = 2)
      and parturients over 50 years to control for egg donation (n = 26).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Male-to-female sex ratio.
      RESULT(S): The male-to-female sex ratio of all the newborns was 1.05. This ratio
      did not change significantly with either maternal or paternal age. Neither
      gravidity nor parity affected the male-to-female ratio. The only factor that
      affected the regression of sex ratio was the length of gestation. CONCLUSION(S):
      Sex ratio at birth is remarkably constant. No association was found between
      parental age or birth order and neonatal sex ratio.

PMID- 19159876
TI  - Facilitation of biliary-wire placement by a stone-extraction balloon.

PMID- 19159877
TI  - Diabetes, Women, and Development: meeting summary, expert recommendations for
      policy action, conclusions, and follow-up actions.

PMID- 19159878
TI  - Episiotomy and third- and fourth-degree perineal tears in primiparous Iranian
      women.

PMID- 19159879
TI  - The nursing implications of routine provider-initiated HIV testing and
      counselling in sub-Saharan Africa: a critical review of new policy guidance from
      WHO/UNAIDS.
AB  - BACKGROUND: In 2007 WHO/UNAIDS issued new HIV testing guidelines recommending
      'provider-initiated HIV testing and counselling' (PITC). In contrast to existing
      'voluntary counselling and testing' guidelines (whereby individuals self refer
      for testing), the PITC guidance recommends that, in countries with generalised
      epidemics, all patients are routinely offered an HIV test during clinical
      encounters. In sub-Saharan Africa, PITC aims to dramatically increase HIV testing
      rates so that PITC becomes a vehicle to increase access to HIV prevention and
      care. Nurses in this region work on the frontlines of HIV testing but have been
      neglected in related policy development. AIM: To provide an overview of the PITC
      policy guidance and to critically consider its implications for the nursing
      profession in sub-Saharan Africa. METHODS: Policy documents and published and
      unpublished research were identified from organisational websites, electronic
      databases and conference proceedings. RESULTS: PITC has generated widespread
      debate about whether it is the right approach in a context of HIV-related stigma
      and lack of human/material resources. Key concerns are whether/how informed
      consent, privacy and confidentiality will be upheld in overstretched health care
      settings, and whether appropriate post-test counselling, treatment and support
      can be provided. Limited available evidence suggests that health systems factors
      and organisational/professional culture may create obstacles to effective PITC
      implementation. Specific findings are that: PITC greatly increases nurses'
      workload and work-related stress. Nurses are generally positive about PITC, but
      express the need for more training and managerial support. Health system
      constraints (lack of staff, lack of space) mean that nurses do not always have
      time to provide adequate counselling. A hierarchical and didactic nursing culture
      affects counselling quality and the boundaries between voluntary informed consent
      and coercion can become rather blurred. Nurses are particularly stressed by
      breaking bad news and handling ethical dilemmas. CONCLUSION: Three areas are
      identified in which the PITC implementation process needs to be strengthened: (i)
      research/audit (to explore nurse and patient experiences, to identify best
      practice and key obstacles), (ii) greater nurse participation in policy
      development, (iii) strengthening of nurse training and mentoring.

PMID- 19159880
TI  - HIV/AIDS preventive self-efficacy, depressive symptoms, and risky sexual behavior
      in adolescents: a cross-sectional questionnaire survey.
AB  - BACKGROUND: High incidence rates of HIV/AIDS infections among youth draw
      attention to the need for emphasizing the reduction of risky sexual behavior, a
      major contributor to the spread of HIV/AIDS. Few researchers have examined the
      relationship between self-efficacy for HIV/AIDS preventions, depressive symptoms,
      and adolescent risky sexual behavior. This insufficient understanding limits
      nurses' ability to provide effective programs for reducing adolescents' risky
      sexual behaviors. OBJECTIVES: This study was conducted to investigate the
      relationships among HIV/AIDS preventive self-efficacy, depressive symptoms, and
      risky sexual behavior in Taiwanese adolescents. DESIGN: A cross-sectional,
      correlational study. SETTINGS: Seven vocational high schools located in a
      metropolitan area in southern Taiwan. PARTICIPANTS: A convenience sample of 16-18
      year-old vocational high school Taiwanese adolescents (n=734) participated in
      this study. METHODS: Several self-administrated questionnaires, including
      HIV/AIDS Preventive Self-efficacy scale, the Center for Epidemiological Studies
      Depression scale, Safe Sex Behavior Questionnaire, and a form for demographic
      data, were used to collect data. RESULTS: Taiwanese adolescents who had higher
      HIV/AIDS preventive self-efficacy scores had less overall risky sexual behavior.
      Adolescents who had less depressive symptoms had higher HIV/AIDS preventive self
      efficacy. More depressive symptoms were correlated to more risky sexual behavior.
      CONCLUSION: Improving Taiwanese adolescents' HIV/AIDS preventive self-efficacy
      could be useful to reduce risky sexual behaviors in this population. Results of
      this study may assist nurses in understanding factors related to adolescents
      HIV/AIDS related risky sexual behavior and its' preventions. However, future
      longitudinal studies are needed to clarify whether depressive symptoms is a major
      influential factor that might interfere with the effectiveness of HIV/AIDS
      prevention programs.

PMID- 19159881
TI  - RCTs in complex nursing interventions and laboratory experimental studies.
AB  - The randomised controlled trial (RCT) is at the heart of the evidence-based
      medicine movement and by implication should also be central to evidence-based
      nursing. One objection to RCTs in nursing science is that nursing is too complex
      an activity to be subjected to a carefully controlled experimental paradigm. We
      suggest that this argument is false and use examples from complex interventions
      research in nursing and experimental laboratory methods to demonstrate that RCTs
      can bring much needed clarity to the search for nursing knowledge.

PMID- 19159882
TI  - Dietary phospholipid-rich dairy milk extract reduces hepatomegaly, hepatic
      steatosis and hyperlipidemia in mice fed a high-fat diet.
AB  - Recent studies have suggested that milk and certain dairy food components have
      the potential to protect against cardiovascular disease. In order to determine
      whether the addition of milk-derived phospholipids to the diet results in an
      improvement in metabolic and cardiovascular risk factors, we studied four groups
      (n=10) of C57BL/6 mice that were fed: (1) a normal non-purified diet (N); (2) the
      normal non-purified diet supplemented with phospholipid-rich dairy milk extract
      (PLRDME, 2.5% by wt) (NPL); (3) a high-fat semi-purified diet (HF) containing 21%
      butterfat+0.15% cholesterol by wt; or (4) HF supplemented with 2.5% by wt PLRDME
      (HFPL). Dietary PLRDME supplementation did not have a significant effect on
      metabolic parameters in mice fed the N diet. In contrast, in high-fat fed mice,
      PLRDME caused a significant decrease in: (a) liver wt (1.57+/-0.06 g vs. 1.20+/
      0.04 g, P<0.001), (b) total liver lipid (255+/-22 mg vs. 127+/-13 mg, P<0.001,
      (c) liver triglyceride (TG) and total cholesterol (TC) 236+/-25 micromol/g vs.
      130+/-8 micromol/g (P<0.01), 40+/-7 micromol/g vs. 21+/-2 micromol/g (P<0.05),
      respectively); and serum lipids (TG: 1.4+/-0.1 mmol/L vs. 1.1+/-0.1 mmol/L,
      P=0.01; TC: 4.6+/-0.2 mmol/L vs. 3.6+/-0.2 mmol/L, P<0.001; and PL: 3.3+/-0.1
      mmol/L vs. 2.6+/-0.1 mmol/L, P<0.01). These data indicate that dietary PLRDME has
      a beneficial effect on hepatomegaly, hepatic steatosis and elevated serum lipid
      levels in mice fed a high-fat diet, providing evidence that PLRDME might be of
      therapeutic value in human subjects as a hepatoprotective or cardioprotective
      nutraceutical.

PMID- 19159883
TI  - Magnetic resonance of carotid artery ageing in healthy subjects.
AB  - OBJECTIVE: To assess how the arterial wall of the carotid artery changes with age
      in normal subjects by cardiovascular magnetic resonance (CMR). METHODS: Carotid
      CMR was performed in 100 normal subjects (10 per sex per decade) who were free of
      atherosclerotic risk factors and carotid atherosclerosis. Using three-dimensional
      computer modeling, the volumes of the arterial wall, lumen, and the total vessel
      were calculated, and the wall/outer wall (W/OW) ratio was derived. RESULTS: Wall
      volume and total vessel volume increased significantly with age in both sexes
      (p<0.006), and this was more marked in males. The W/OW ratio also increased
      significantly with age (p<0.001). Lumen volume increased significantly with age
      in males (p<0.001), but not in females (p=0.1). CONCLUSIONS: In normal subjects,
      carotid wall volume increases with age. In men, this vessel wall volume increase
      is associated with significant remodeling of the lumen and outer wall. These data
      relating normal carotid findings with ageing are important for further CMR
      studies of early atherosclerosis.

PMID- 19159885
TI  - The effect of composition and microstructure on the viscoelastic properties of
      dermis.
AB  - Dermis is a heterogeneous tissue in which extracellular matrix components change
      in relative amount and spatial assembly across the tissue thickness. The effect
      of the microstructural and compositional heterogeneities on the overall
      mechanical response of dermis is, however, largely ignored. In this work, we
      aimed at gaining a better insight into the effect of extracellular matrix
      microstructure and composition on the mechanical behaviour of different dermal
      strata by combining mechanical analysis and selective enzymatic digestion of
      extracellular matrix components. The dynamical-mechanical tests we performed on
      bovine dermal splits show that the upper dermal stratum, which is richer in
      papillary dermis, is characterized by higher mechanical properties than the lower
      one, which is almost composed of reticular dermis. Moreover, the depletion of
      interfibrillar proteins, proteoglycans and glycosamminoglycans decreases the
      dynamic moduli of dermis, especially at small frequencies. Of the two dermal
      layers tested, the upper dermal layer is more sensitive to the enzymatic
      treatment than the lower layer. Interestingly, the disruption of the elastic
      network greatly influenced the viscoelastic properties of upper dermis, inducing
      a dramatic decrease of both storage (G') and loss (G'') moduli, suggesting that
      the spatial assembly of the elastin and collagen networks as well as their mutual
      interactions dominate the dynamical mechanical response of the tissue.

PMID- 19159884
TI  - Elevated alanine aminotransferase levels predict mortality from cardiovascular
      disease and diabetes in Koreans.
AB  - OBJECTIVE: Metabolic syndrome is associated with increased cardiovascular
      morbidity and mortality. Nonalcoholic fatty liver disease (NAFLD) is closely
      associated with metabolic syndrome. This study investigated the relationship
      between elevated alanine aminotransferase (ALT) levels, as a proxy marker of
      NAFLD, and death from cardiovascular disease (CVD) or diabetes in a Korean
      population. METHODS: The study population consisted of 37,085 patients who
      underwent health examinations at the Health Promotion Center of the Asan Medical
      Center, Seoul, Korea, in 2000 and 2001. Individuals with viral hepatitis or
      alcoholic liver disease were excluded from the study. The relationship between
      baseline ALT levels and CVD- or diabetes-related mortality was determined for a
      median period of 5.0 years. RESULTS: A total of 407 deaths occurred during the
      follow-up period, with 91 deaths resulting from CVD or diabetes. The multivariate
      relative risk (RR) and 95% confidence interval (CI) for CVD- or diabetes-related
      mortality in patients with ALT levels >40IU/L were 2.26 (1.22-4.19). The
      multivariate RR and 95% CI for CVD- or diabetes-related mortality in patients
      with the highest quartile of ALT levels (> or =31IU/L) were 2.28 (95% CI: 1.02
      5.08) when the lowest quartile (< or =15IU/L) was used as a reference.
      CONCLUSION: Our findings demonstrate that elevated ALT levels are independently
      associated with increased CVD- or diabetes-related mortality in Koreans. Thus,
      elevated ALT levels, as a marker for NAFLD, may serve as a surrogate predictor of
      CVD- or diabetes-related mortality among the Korean population.

PMID- 19159886
TI  - Intestinal remodelling in mink fed with reduced protein content.
AB  - Low protein intake occurs in humans in relation to diseases, starvation and post
      operatively. Low-protein diets may affect the gastrointestinal structure and
      mechanical function. The aim was to study the passive biomechanical properties
      and tissue remodelling of the intestine in minks on reduced protein diets. Twenty
      seven male minks were divided into three groups receiving different protein level
      in the diet for 6 weeks: High protein level (group H, 55% energy from protein),
      moderate protein level (group M, 30% energy from protein) and low protein level
      (group L, 15% energy from protein) (n=9 for each group). Ten centimetre long
      segments from duodenum, jejunum and ileum were excised at the end of the study
      period. The mechanical test was performed as a ramp distension experiment. The
      intestinal diameter and length, wall thickness, wall area and opening angle were
      obtained from digitized images of the intestinal segments at pre-selected
      pressures, no-load and zero-stress states, respectively. Circumferential and
      longitudinal stresses (force per area) and strains (deformation) were computed.
      The layer thickness was measured from intestinal histological images. No
      difference in body weight was found between groups at the start of the
      experiment. However, at the end of the experiment the body weight was smallest in
      group L (P=0.0003 and 0.0004 compared with groups H and M). Similarly, the wet
      weight per unit length, wall thickness and area were smallest in group L (P<0.05,
      P<0.01). The lowest wall thickness was found in the jejunum and ileum in group L
      (P<0.05), mainly due to decreased mucosa and submucosa thickness. The smallest
      opening angle and absolute values of residual strain were found in the jejunal
      segment in group L (P<0.05). No difference was observed for duodenal and ileal
      segments among the three groups. Feeding the low-protein diet shifted the stress
      strain curves to the right for the circumferential direction, indicating the wall
      become softer in the circumferential direction. However, no significant
      difference was observed in the longitudinal direction for any of the intestinal
      segments. In conclusion, this study demonstrated that low-protein diet in minks
      induce histomorphometric and biomechanical remodelling of the intestine.

PMID- 19159887
TI  - On parameter estimation for biaxial mechanical behavior of arteries.
AB  - This article considers the parameter estimation of multi-fiber family models for
      biaxial mechanical behavior of passive arteries in the presence of the
      measurement errors. First, the uncertainty propagation due to the errors in
      variables has been carefully characterized using the constitutive model. Then,
      the parameter estimation of the artery model has been formulated into nonlinear
      least squares optimization with an appropriately chosen weight from the
      uncertainty model. The proposed technique is evaluated using multiple sets of
      synthesized data with fictitious measurement noises. The results of the
      estimation are compared with those of the conventional nonlinear least squares
      optimization without a proper weight factor. The proposed method significantly
      improves the quality of parameter estimation as the amplitude of the errors in
      variables becomes larger. We also investigate model selection criteria to decide
      the optimal number of fiber families in the multi-fiber family model with respect
      to the experimental data balancing between variance and bias errors.

PMID- 19159888
TI  - Temperature-dependent viscoelastic properties of the human supraspinatus tendon.
AB  - Temperature effects on the viscoelastic properties of the human supraspinatus
      tendon were investigated using static stress-relaxation experiments and the quasi
      linear viscoelastic (QLV) theory. Twelve supraspinatus tendons were randomly
      assigned to one of two test groups for tensile testing using the following
      sequence of temperatures: (1) 37, 27, and 17 degrees C (Group I, n=6), or (2) 42,
      32, and 22 degrees C (Group II, n=6). QLV parameter C was found to increase at
      elevated temperatures, suggesting greater viscous mechanical behavior at higher
      temperatures. Elastic parameters A and B showed no significant difference among
      the six temperatures studied, implying that the viscoelastic stress response of
      the supraspinatus tendon is not sensitive to temperature over shorter testing
      durations. Using regression analysis, an exponential relationship between
      parameter C and test temperature was implemented into QLV theory to model
      temperature-dependent viscoelastic behavior. This modified approach facilitates
      the theoretical determination of the viscoelastic behavior of tendons at
      arbitrary temperatures.

PMID- 19159889
TI  - Advancement in analysis of Salviae miltiorrhizae Radix et Rhizoma (Danshen).
AB  - This review summarizes the recent advances in the chemical analysis of Danshen
      and its finished products, including the introduction of the identified bioactive
      components, analytical methods for quantitative determination of target analytes
      and fingerprinting authentication, quality criteria of Danshen crude herb and its
      preparations, as well as the pharmacokinetic and pharmacodynamic studies on the
      active components of Danshen and its finished products. Danshen contains mainly
      two types of constituents, the hydrophilic depsides and lipophilic diterpenoidal
      quinones and both of them are responsible for the pharmacological activities of
      Danshen. In order to monitor simultaneously both types of components which have
      different physicochemical properties, numerous analytical methods have been
      reported using various chromatographic and spectrophotometric technologies. In
      this review, 110 papers on analysis of Danshen are discussed, various analytical
      methods and their chromatographic conditions are briefly described and their
      advantages/disadvantages are compared. For obtaining a quick, accurate and
      applicable analytical approach for quality evaluation and establishing a
      harmonized criteria of Danshen and its finished products, the authors' suggestion
      and opinions are given, including the reasonable selection of marker compounds
      with high concentration and commercial availability, a simple sample preparation
      procedure with high recoveries of both the hydrophilic phenols and lipophilic
      tanshinones, and an optimized chromatographic condition with ideal resolutions of
      all the target components. The chemical degradation and transformation of the
      predominant constituent salvianolic acid B in Danshen during processing and
      manufacturing are also emphasized in order to assure the quality consistency of
      Danshen containing products.

PMID- 19159890
TI  - Online preconcentration of recombinant Arg-Gly-Asp-hirudin using dynamic pH
      junction for analysis in human urine samples by capillary electrophoresis-mass
      spectrometry.
AB  - A sensitive and effort-saving method was established and validated for the
      quantitative determination of recombinant Arg-Gly-Asp-hirudin (rRGD-hirudin) in
      human urine samples. The assay was performed on a uncoated fused silica capillary
      of 70 cm x 50 microm I.D. and a positive voltage of 30 kV was applied. The sample
      was injected under pressure of 50 mbar for 300 s and the temperature of capillary
      was kept 25 degrees C. Sheath liquid consisting of 30% methanol and 70% of 0.1%
      formic acid aqueous solution flowing at 7 microL/min was supplied to the CE
      electrospray interface. Utilizing the dynamic pH junction technique, a lower
      limit of quantitation of approximately 35 nM was achieved (concentration
      coefficiency was about 100-fold) without complex sample preprocessing procedure.
      CE-MS conditions and parameters were also optimized to obtain better performance.
      The method has been successfully applied in clinical research of rRGD-hirudin.

PMID- 19159891
TI  - Chromatographic and spectroscopic studies on the chiral recognition of sulfated
      beta-cyclodextrin as chiral mobile phase additive enantiomeric separation of a
      chiral amine.
AB  - A fast enantiomeric separation of a chiral aromatic amine was achieved, using
      ultra high pressure liquid chromatography and highly sulfated beta-cyclodextrin
      (S-beta-CD) as a chiral additive in the mobile phase. The stationary phase
      consisted of a core-shell support with a particle size of 2.7mum. Under these
      conditions the base-line separation was obtained within 2.5min. The influence of
      the concentration of the additive, along with the thermodynamics of the
      separation, was studied. Vibrational circular dichroism (VCD) spectroscopy was
      applied to assess the absolute configuration of the two enantiomeric analytes, as
      well as the interaction of these enantiomers with the S-beta-CD. The VCD results
      revealed that S-beta-CD undergoes a temperature-induced conformational change.
      Further, VCD experiments indicate that the interactions of the two enantiomers
      with the S-beta-CD occur through an inclusion of the aromatic part of the
      analyte, as well as through electrostatic interaction between the protonated
      amine and the sulfate groups located at the narrow part of the S-beta-CD.
      Molecular mechanics calculations performed according to the VCD results are
      consistent with experimental data, providing further evidence of these
      interactions.

PMID- 19159892
TI  - Deformation of PDMS membrane and microcantilever by a water droplet: comparison
      between Mooney-Rivlin and linear elastic constitutive models.
AB  - In this paper, we studied the role of vertical component of surface tension of a
      water droplet on the deformation of membranes and microcantilevers (MCLs) widely
      used in lab-on-a-chip and micro- and nano-electromechanical system (MEMS/NEMS).
      Firstly, a membrane made of a rubber-like material, poly(dimethylsiloxane)
      (PDMS), was considered. The deformation was investigated using the Mooney-Rivlin
      (MR) model and the linear elastic constitutive relation, respectively. By
      comparison between the numerical solutions with two different models, we found
      that the simple linear elastic model is accurate enough to describe such kind of
      problem, which would be quite convenient for engineering applications.
      Furthermore, based on small-deflection beam theory, the effect of a liquid
      droplet on the deflection of a MCL was also studied. The free-end deflection of
      the MCL was investigated by considering different cases like a cylindrical
      droplet, a spherical droplet centered on the MCL and a spherical droplet
      arbitrarily positioned on the MCL. Numerical simulations demonstrated that the
      deflection might not be neglected, and showed good agreement with our theoretical
      analyses.

PMID- 19159893
TI  - Spectroscopic evaluation of surface functionalization efficiency in the
      preparation of mercaptopropyltrimethoxysilane self-assembled monolayers on glass.
AB  - Four synthetic protocols have been examined for the preparation of a self
      assembled monolayer of propanethiol functions on glass surfaces, through the wet
      reaction of mercaptopropyltrimethoxysilane (MPTS) on glass slides, in order to
      determine an optimal method to obtain dense -SH monolayers for further reaction
      with maleimide-bearing molecules. We have also demonstrated that the surface
      density of reactive -SH groups can be indagated by the coupling reaction with a
      maleimide-functionalized rhodamine dye and by the examination of the absorption
      spectra of the glass slides. The reaction of MPTS in dry toluene gives the most
      dense surface of reactive thiols, among the examined protocols. We have also
      evidenced that thermal curing of the MPTS functionalized slides induces thiol
      coupling and -S-S- formation, resulting in a dramatically lowered availability of
      -SH groups.

PMID- 19159894
TI  - Preparation of silica stabilized Tobacco mosaic virus templates for the
      production of metal and layered nanoparticles.
AB  - The use of biological molecules as templates for the production of metal
      nanoparticles and wires is often limited by the stability of the bio-template and
      its affinity for nucleating metal deposition. In this study, Tobacco mosaic virus
      (TMV) was used as a model bio-template to investigate the use of silica coatings
      as a means to both enhance template stability and increase its affinity for metal
      ions. Results indicate that the unmodified TMV particle can function as a
      template for the growth of thin (<1 nm) silica layers. However, this thin silica
      shell did not enhance the stability of the template during metal deposition. To
      increase silica growth on the TMV template, a pretreatment with aniline was used
      to produce a uniform silica attractive surface. Aniline pretreated templates
      yielded significant silica layers of >20 nm in thickness. These silica shells
      conferred a high degree of stability to the TMV particle and promoted the
      deposition of various metal nanoparticles through conventional silica
      mineralization chemistries. This process provides a simple and robust method for
      the layering of inorganics onto a biological template.

PMID- 19159895
TI  - Catalytic activity of rare earth phosphates for SF(6) decomposition and promotion
      effects of rare earths added into AlPO(4).
AB  - SF(6) was selectively hydrolyzed to SO(3) over rare earth (RE) phosphates above
      800 K. CePO(4) was the most active catalyst, followed by GdPO(4), YbPO(4),
      DyPO(4), ErPO(4), SmPO(4), PrPO(4), TbPO(4), NdPO(4), and LaPO(4). The middle RE
      phosphates were found to be more active than the light RE phosphates, but the
      reason for the high activity of CePO(4), which belongs to the light RE group, is
      not clear. The catalytic activity was independent of the specific surface area
      (SSA), acid amount, and acid concentration of the catalysts. RE phosphates were
      single-phase, and a broad inversely proportional relation was observed between
      the crystallite size and SSA, except in the case of CePO(4). The combination of
      highly active AlPO(4) and CePO(4) creates synergetic effects in the catalytic
      activity and SO(3) selectivity over all ranges of composition. Binary catalysts
      were a mixture of small crystalline AlPO(4) and CePO(4). The addition of Ce
      promoted the crystallization of AlPO(4), which was controlled to about 10 nm at
      10-50% Ce content. The turnover frequency for SF(6) decomposition was
      proportional to the surface concentration of hydroxyls of binary catalysts.
      Therefore, synergy effects may come from the number of hydroxyl (OH) pair sites
      on which a bidentate intermediate of hydrolysis of SF(6) may be formed by the
      moderate crystallization of AlPO(4). The addition of Ce, Pr, or Y to AlPO(4)
      brings about a small promotion effect for SF(6) decomposition, but the addition
      of La, Nd > Gd > Yb diminishes the activity. The addition of Gd, Pr, or Nd
      greatly improved the SO(3) selectivity. A linear relationship between catalytic
      activity and the concentration of surface hydroxyls of the catalysts supports a
      reaction mechanism in which two F atoms of an SF(6) molecule interact with two
      surface hydroxyls to form a bidentate intermediate.

PMID- 19159896
TI  - Diffuse sorption modeling.
AB  - This work presents a simple solution for the diffuse double layer model,
      applicable to calculation of surface speciation as well as to simulation of ionic
      adsorption within the diffuse layer of solution in arbitrary salt media. Based on
      Poisson-Boltzmann equation, the Gaines-Thomas selectivity coefficient for uni
      bivalent exchange on clay,
      K(GT)(Me(2+)/M(+))=(Q(Me)(0.5)/Q(M)){M(+)}/{Me(2+)}(0.5), (Q is the equivalent
      fraction of cation in the exchange capacity, and {M(+)} and {Me(2+)} are the
      ionic activities in solution) may be calculated as [surface charge,
      mueq/m(2)]/0.61. The obtained solution of the Poisson-Boltzmann equation was
      applied to calculation of ionic exchange on clays and to simulation of the
      surface charge of ferrihydrite in 0.01-6 M NaCl solutions. In addition, a new
      model of acid-base properties was developed. This model is based on assumption
      that the net proton charge is not located on the mathematical surface plane but
      diffusely distributed within the subsurface layer of the lattice. It is shown
      that the obtained solution of the Poisson-Boltzmann equation makes such
      calculations possible, and that this approach is more efficient than the original
      diffuse double layer model.

PMID- 19159897
TI  - Ovine small intestinal adenocarcinomas are not associated with infection by
      herpesviruses, Helicobacter species or Mycobacterium avium subspecies
      paratuberculosis.
AB  - Sheep in New Zealand more frequently develop small intestinal adenocarcinoma
      (SIA) than sheep in other countries. The reasons for this high rate of intestinal
      neoplasia are not known. In man, differences between countries in the incidence
      of neoplasia are often due to differences in the rate of infection by
      carcinogenic viruses or bacteria. Therefore, it was hypothesized that New Zealand
      sheep more frequently develop SIA as they are more frequently exposed to an
      infectious agent. This study compared rates of detection of herpesviruses,
      Helicobacter species, and Mycobacterium avium subspecies paratuberculosis (MAP)
      in ovine SIA to rates of detection in samples of intestine with non-neoplastic
      disease. These infectious agents were chosen as all three have been associated
      with human intestinal cancer. Microscopical examination did not reveal helical
      bacteria within sections of SIA or non-neoplastic jejunum. Polymerase chain
      reaction amplified herpesviral DNA more frequently from samples of non-neoplastic
      jejunum than samples of SIA. MAP DNA was not amplified from either neoplastic or
      non-neoplastic jejunum. These results suggest that the high rates of SIA in New
      Zealand sheep are not due to frequent infection by herpesviruses, Helicobacter
      species or MAP.

PMID- 19159898
TI  - Acute megakaryocytic leukaemia (AMKL)-like disease in a cynomolgus monkey (Macaca
      fascicularis).
AB  - A 5-year-old male cynomolgus monkey (Macaca fascicularis) with a clinical history
      of bleeding tendency, severe anaemia, thrombocytopenia and elevated serum
      concentration of liver-related enzymes was examined post mortem. Ecchymotic
      haemorrhages were present on the left eyelid and forehead. The liver, kidney and
      spleen were markedly enlarged and the kidneys had capsular petechiae.
      Microscopically, numerous atypical cells resembling myeloid cells were observed
      in the bone marrow, and myelofibrosis was present. Atypical cells were also
      present in the blood vessels of the liver, kidney, spleen, lymph nodes, lung,
      heart, bladder, adrenal gland and brain. Some neoplastic cells had oval or
      pleomorphic macronuclei and others were multinucleated. Immunohistochemically,
      the majority of the neoplastic cells had granular cytoplasmic expression of the
      megakaryocyte-associated antigens Von Willebrand Factor and CD61-IIIa, but were
      negative for myeloperoxidase. A diagnosis of acute megakaryocytic leukaemia
      (AMKL)-like disease was made. This would appear to be the first report of AMKL
      like disease in non-human primates. This monkey was infected with simian
      retrovirus type D and it is possible that this viral infection was associated
      with the development of neoplasia.

PMID- 19159899
TI  - The Dipolar ElectroCARdioTOpographic (DECARTO)-like method for graphic
      presentation of location and extent of area at risk estimated from ST-segment
      deviations in patients with acute myocardial infarction.
AB  - A graphic method was developed for presentation of the location and extent of the
      myocardium at risk in patients with acute myocardial infarction (AMI). This
      method is based on a mathematical processing of ST-segment deviations of standard
      12-lead electrocardiogram following the concept of Titomir and Ruttkay-Nedecky in
      their dipolar electrocardiotopographic method. The center of the location of the
      area at risk is given by the spatial orientation of the resultant spatial ST
      vector, and the extent of the area at risk is derived from the Aldrich score. The
      areas at risk are projected on a spherical image surface, on which a texture of
      the anatomical quadrants of the ventricular surface and its coronary artery
      supply are projected. The method was tested in 10 patients with AMI with single
      vessel disease, including 6 patients with an occlusion in the proximal left
      anterior descending coronary artery (LAD), 3 patients with an occlusion in the
      right coronary artery, and one patient with occlusion in the left circumflex
      coronary artery. The estimated areas at risk were compared with myocardial
      perfusion single photon emission computed tomography. Eight (80%) patients of 10
      were correctly localized according to the Aldrich decision rules for the location
      of AMI. The areas at risk in patients with LAD occlusion correctly localized by
      the Aldrich score were situated in the anteroseptal and anterosuperior quadrants.
      In the inferior AMI group, the area at risk was localized in the posterolateral
      and inferior quadrants. The visual comparison with myocardial perfusion single
      photon emission computed tomography (SPECT) showed best agreement in patients
      with LAD involvement. The initial testing showed that this method allows a
      graphic presentation of estimated area at risk using clinically defined
      diagnostic rules. The area at risk can be displayed in images that are familiar
      for clinicians and can be compared with or superimposed on results of other
      imaging methods used in cardiology.

PMID- 19159900
TI  - Distorted T-vector loop and increased heart rate are associated with ventricular
      fibrillation in a porcine ischemia-reperfusion model.
AB  - BACKGROUND: The ventricular repolarization (VR) response to short-lasting
      coronary occlusion has been characterized by 3-dimensional vectorcardiography
      during angioplasty in humans; the T-vector loop becomes distorted (increased
      T(avplan)) and more circular (decreased T(eigenvalue)), but these changes have
      not been related to ventricular arrhythmias. PURPOSE: The VR response was
      therefore explored in a porcine ischemia-reperfusion model and compared in pigs
      with (n = 16) vs without (n = 17) ventricular fibrillation (VF). METHODS:
      Different aspects of VR were evaluated at baseline, at maximum ischemia, before
      reperfusion and at the subsequent ST maximum, after 1 hour of reperfusion, and
      before VF. Three aspects of the VR response were assessed: the ST-segment, the T
      vector angles, and the T-vector loop morphology. RESULTS: All parameters changed
      significantly from baseline during ischemia and/or reperfusion. The early changes
      were similar to those previously observed in humans during angioplasty. The VF
      episodes were preceded by a significantly exaggerated T-loop distortion
      (increased T(avplan)) and increased heart rate. CONCLUSION: Aggravated T-loop
      distortion might, in this porcine ischemia-reperfusion model, reflect aspects of
      VR relevant to arrhythmogenesis.

PMID- 19159901
TI  - Comparison of the correlation of the Selvester QRS scoring system with cardiac
      contrast-enhanced magnetic resonance imaging-measured acute myocardial infarct
      size in patients with and without thrombolytic therapy.
AB  - BACKGROUND: After an acute myocardial infarction (MI), it is important to define
      the infarct size because it is related to mortality and morbidity. The Selvester
      QRS Score is an electrocardiographic (ECG) method that has been developed for
      estimating MI size. It has been shown to correlate well with postmortem
      anatomically measured sizes of single MI in patients who did not receive
      thrombolytic therapy. The aim of this study was to test the hypothesis that
      correlation between Selvester QRS Score-estimated MI size and contrast-enhanced
      magnetic resonance imaging (ceMRI)-measured MI size is equivalent in patients who
      did vs those who did not receive thrombolytic therapy. METHODS: Thirty-six
      patients with MI (24 with thrombolytic therapy and 12 without) received ceMRI and
      ECG at admission and at 1 or 6 months after admission. Indeed, in 23 of the
      patients, the therapy was intravenous only. The Selvester QRS Score was
      calculated using the 1-month ECG or, if not available, the 6-month ECG. The
      correlation between the 2 measures of MI size was determined for all patients and
      for the 2 groups separately. RESULTS: The mean MI size in the group that did not
      receive thrombolytic therapy was 8.5% +/- 6.4% estimated by the Selvester QRS
      Score and 11.7% +/- 10.2% measured by ceMRI. For the group that received
      thrombolytic therapy, Selvester QRS Score was 13.9% +/- 11.1% and ceMRI was 20.2%
      +/- 11.3%. The mean MI size in both groups combined was 12.1% +/- 10.0% estimated
      by the Selvester QRS Score and 17.3% +/- 11.5% measured by ceMRI. The Spearman
      rank correlation coefficient between Selvester QRS Score and ceMRI was 0.74 (P <
      .0001) for all patients, 0.74 (P < .0001) for the group that received
      thrombolytic therapy, and 0.64 (P = .024) for the group that did not receive
      thrombolytic therapy. CONCLUSIONS: The associations between Selvester QRS Score
      and ceMRI-based MI were statistically significant and similar in both groups.

PMID- 19159902
TI  - Development of an automated method for display of ischemic myocardium from
      simulated electrocardiograms.
AB  - BACKGROUND: Knowledge of the size and location of ischemic myocardium during
      acute coronary occlusion could provide decision support before reperfusion
      therapy. Electrocardiogram (ECG) scores based on the number of leads and the sum
      of ST-segment elevation have been unreliable in quantifying ischemia. We aimed to
      develop a new method to graphically display ischemic myocardium from simulated
      ECGs (DIMS-ECG) associated with known ischemic regions. METHODS: Twenty-one
      patterns of ischemia based on normal coronary anatomy were programmed into the
      freely available program ECGSIM (www.ecgsim.org). Minor variations of these
      patterns and 5 levels of ischemia severity produced 45 455 ECGs; 1000 normal ECGs
      were also added. Given a de novo ECG (an ECG from a patient), ST-segment and T
      wave measurements are compared with ECG measurements in the database. The closest
      200 matches are selected, and the corresponding ischemic areas are "averaged" to
      create a graphical display of the ischemic myocardium. RESULTS: Three patients
      are presented who underwent elective coronary angioplasty with continuous ECG
      recording and scintigraphically defined ischemic myocardium. Based on ECG
      analysis, the program graphically displays the ischemic myocardium with close
      agreement to the scintigraphic images. The program's source code and the ECG
      database will be made freely available. CONCLUSIONS: The DIMS-ECG method
      graphically displays ischemic myocardium from information contained in the 12
      lead ECG based on a novel approach to use a large simulated database instead of
      rule- or score-based method. After further development and testing, the DIMS-ECG
      method could be used to risk stratify patients with acute myocardial infarction.

PMID- 19159903
TI  - The ST Compass: spatial visualization of ST-segment deviations and estimation of
      the ST injury vector.
AB  - The current electrocardiogram criteria for the diagnosis of transmural myocardial
      ischemia focus on ST elevations, although anterior lead ST depression may be
      indicative of posterior ischemia. ST elevation and depression in different leads
      may be considered different projections of a common ST injury current directed
      toward areas of transmural ischemia. To facilitate vectorial analysis of ST
      deviations, we present the ST Compass-a new tool for visualization of ST
      deviations from standard 12-lead electrocardiograms. We also present a method to
      estimate a vector describing the magnitude and direction of the underlying ST
      injury current based on the observed ST deviations. In 2 cases of acute
      myocardial infarction, the ST deviation vectors form a clear pattern in the ST
      Compass, and the spatial direction of the ST injury current corresponds to the
      location of myocardial ischemia as confirmed by single-photon emission computed
      tomography imaging.

PMID- 19159904
TI  - Electrocardiographic alterations after chronic right ventricular apical pacing in
      patients with sinus node dysfunction.
AB  - OBJECTIVE: The purpose of this study is to investigate the potential to induce
      electrical remodeling by chronic right ventricular apical (RVA) in patients with
      sinus node dysfunction. METHODS: Ninety-two patients with sinus node dysfunction
      who underwent initial pacemaker implantation were included in the study. During
      routine clinic visits, electrocardiograms and echocardiograms were recorded.
      Forty-five patients were also studied as controls. RESULTS: During a mean follow
      up time of 3.3 +/- 0.5 years, the intrinsic QRS duration increased from 87 +/- 9
      milliseconds before device implantation to 94 +/- 10 milliseconds (P < .001). The
      left ventricular end-diastolic diameter increased from 46 +/- 3 to 50 +/- 4 mm (P
      < .001), and the left ventricular ejection fraction decreased from 63% +/- 4% to
      57% +/- 5% (P < .001). Logistic regression analysis revealed that elderly age at
      the time of pacemaker implantation (odds ratio [OR], 3.41; 95% confidence
      interval [CI], 1.07-10.90; P = .04), RVA pacing (OR, 3.91; 95% CI, 1.10-13.89; P
      = .03), and coronary artery disease (OR, 7.33; 95% CI, 1.09-50.29; P = .04) were
      independent predictors of the prolongation of intrinsic QRS duration.
      CONCLUSIONS: The present study indicated that chronic RVA pacing may lead to a
      prolongation of intrinsic QRS duration, which could be independently predicted by
      elderly age, chronic RVA pacing, and the presence of coronary artery disease.

PMID- 19159905
TI  - Parainfluenza virus infection of young children: estimates of the population
      based burden of hospitalization.
AB  - OBJECTIVE: To determine the population-based inpatient disease burden of
      parainfluenza virus in children <5 years of age. STUDY DESIGN: The New Vaccine
      Surveillance Network (NVSN) enrolled children <5 years of age who were
      hospitalized with febrile or acute respiratory illnesses. Surveillance hospitals
      admitted >95% of all hospitalized children from each county. Combined nasal
      turbinate/throat swabs were tested for parainfluenza virus (PIV), respiratory
      syncytial virus, and influenza virus with culture and reverse-transcription
      polymerase chain reaction. Both parental interviews and medical chart reviews
      were conducted. Age-specific population-based hospitalization rates were
      calculated. RESULTS: From October 2000 through September 2004, 2798 children were
      enrolled. A total of 191 PIVs were identified from 189 children (6.8% of
      enrolled: 73 PIV type 1, 23 PIV type 2, and 95 PIV type 3), compared with 521
      respiratory syncytial viruses and 159 influenza viruses. Mean PIV hospitalization
      rates were 3.01, 1.73, 1.53, 0.39, and 1.02 per 1000 children per year for ages 0
      to 5 months, 6 to 11 months, 12 to 23 months, 24 to 59 months, and 0 to 59
      months, respectively. CONCLUSIONS: PIV accounted for 6.8% of all hospitalizations
      for fever, acute respiratory illnesses, or both in children <5 years of age. The
      pediatric PIV inpatient burden is substantial and highlights the need to find an
      effective vaccine candidate.

PMID- 19159906
TI  - Immunopathology of chronic rhinosinusitis in young children.
AB  - OBJECTIVE: Previous investigation demonstrated predominantly lymphocytic
      inflammation in sinus mucosa of young children with chronic rhinosinusitis (CRS)
      rather than eosinophilic inflammation typical of adult CRS.
      Immunohistopathological study was undertaken to define further the cellular
      response in pediatric CRS. STUDY DESIGN: Maxillary mucosal biopsies from children
      and adults with CRS were stained for CD3 (T lymphocytes), CD4 (helper T
      lymphocytes), CD8 (cytotoxic T lymphocytes), CD20 (B lymphocytes), CD68
      (monocytes/macrophages), CD56 (natural killer cells), kappa and lambda (plasma
      cells), and myeloperoxidase (MPO; neutrophils). RESULTS: Nineteen children with
      CRS (median age, 3.0 years; range, 1.4-8.2 years) had more CD8+, MPO+, and CD68+
      cells (P < or = .03) and a trend toward more CD3+ and CD4+ cells (P = .06) in
      their epithelium and more CD20+, kappa+ and lambda+, MPO+, and CD68+ cells (P <
      or = .05) and a trend toward more CD4+ cells (P = .06) in their submucosa
      compared with adult control subjects. Immunostains from children with positive
      sinus cultures were similar to those with negative cultures except for more MPO+
      cells in the submucosa (P = .04). CONCLUSION: The inflammatory response of young
      children with CRS is characterized by a mixed lymphocyte population, macrophages,
      and neutrophils. Differences between pediatric and adult CRS suggest differing
      pathogenic mechanisms or progression in the inflammatory response with protracted
      disease.

PMID- 19159907
TI  - Methotrexate in pediatric osteosarcoma: response and toxicity in relation to
      genetic polymorphisms and dihydrofolate reductase and reduced folate carrier 1
      expression.
AB  - OBJECTIVE: To determine the influence of the genotype and the level of expression
      of different enzymes involved in folate metabolism on the response to and
      toxicity of high-dose methotrexate treatment in pediatric osteosarcomas. STUDY
      DESIGN: DHFR and Reduced folate carrier 1 (RFC1) semiquantitative expression was
      analyzed in 34 primary and metastatic osteosarcoma tissues by real-time
      polymerase chain reaction. The following polymorphisms were also analyzed in
      peripheral blood from 96 children with osteosarcoma and 110 control subjects:
      C677T, A1298C (MTHFR), G80A (RFC1), A2756G (MTR), C1420T (SHMT), the 28bp-repeat
      polymorphism, and 1494del6 of the TYMS gene. Treatment toxicity was scored after
      each cycle according to criteria from the World Health Organization. RESULTS:
      DHFR and RFC1 expression was lower in initial osteosarcoma biopsy specimens than
      in metastases (P = .024 and P = .041, respectively). RFC1 expression was
      moderately decreased in samples with poor histologic response to preoperative
      treatment (P = .053). Patients with osteosarcoma with G3/G4 hematologic toxicity
      were more frequently TT than CT/CC for C677T/MTHFR (P = .023) and GG for
      A2756G/MTR (P = .048 and P = .057 for gastrointestinal and hematologic toxicity,
      respectively). CONCLUSIONS: The role of C677T/MTHFR and A2756G/MTR on
      chemotherapy-induced toxicity should be further investigated in pediatric
      osteosarcomas receiving high-dose methotrexate. Altered expression of DHFR and
      RFC1 is a feasible mechanism by which osteosarcoma cells become resistant to
      methotrexate.

PMID- 19159908
TI  - Rho-kinase inhibitor attenuates cholestasis-induced CXC chemokine formation,
      leukocyte recruitment, and hepatocellular damage in the liver.
AB  - BACKGROUND: In the present experimental study, we analyzed the role of Rho-kinase
      during obstructive cholestasis by studying the effect of the Rho-kinase inhibitor
      Y-27632 on hepatic CXC chemokine formation, leukocyte recruitment and
      hepatocellular damage. MATERIALS AND METHODS: C57BL/6 mice underwent bile duct
      ligation (BDL) to induce obstructive cholestasis. Mice were pretreated with Y
      27632 (1 and 10mg/kg) or the vehicle PBS. Sham-operated animals served as
      controls. After 12h, hepatic accumulation of leukocytes and sinusoidal perfusion
      were determined using intravital fluorescence microscopy. Hepatocellular damage
      was monitored by measuring serum levels of alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST). CXC chemokines in the liver were analyzed by
      ELISA. RESULTS: Administration of 10mg/kg of Y-27632 protected against
      cholestasis-induced hepatocellular damage indicated by a more than 87% reduction
      of ALT and AST in BDL mice. Moreover, this Rho-kinase inhibitor significantly
      decreased BDL-induced production of CXC chemokines by 44-83% and leukocyte
      recruitment by 60%. Finally, treatment with Y-27632 restored sinusoidal perfusion
      in cholestatic animals. CONCLUSIONS: Our findings indicate that the Rho-kinase
      signaling pathway plays a key role in the pathophysiology of cholestatic liver
      injury. Thus, targeting Rho-kinase activity may represent a new therapeutic
      approach in the treatment of inflammation and liver injury in cholestatic liver
      diseases.

PMID- 19159909
TI  - Integrating surgical skills education into the anatomy laboratory.
AB  - BACKGROUND: Preclinical education plays a pivotal role in improving the quality
      of patient care and safety. Early exposure to surgical skills training and
      surgical mentors enhance students' retention and confidence in those skills, and
      may promote their interest in surgery. METHODS: Based upon a needs assessment
      survey of surgical education at UCSF, we introduced a curriculum to teach basic
      surgical techniques in the preclinical years with the intent of emphasizing
      several important skills and providing students with exposure to surgical mentors
      in a small group environment. We then surveyed the students to assess
      satisfaction with the new curriculum and the effect on perceptions regarding a
      career in surgery. RESULTS: Rising fourth y students at UCSF identified the need
      for increased exposure to basic surgical skills in preparation for third y
      clerkships. Collaboration between the Departments of Anatomy and Surgery
      subsequently produced an integrated suturing curriculum in the anatomy lab as
      part of the first y medical school coursework. The curriculum offered a focused
      exposure to skills identified by senior students as important for their clinical
      rotations. The vast majority of respondents agreed or strongly agreed that the
      exercise was enjoyable and worth continuing, and that their interactions with the
      surgeon volunteers were positive. Furthermore, 33% stated that their interest in
      surgery increased after the exercise. Qualitative comments praised both the
      experience and surgical faculty participation. CONCLUSION: A needs-based surgical
      skills curriculum can be integrated into the traditional first-y anatomy course
      without detracting from didactic instruction in anatomy. Furthermore, students
      received early exposure to surgical mentors and skills training, which may
      translate into greater confidence on the wards and increased interest in surgical
      careers.

PMID- 19159910
TI  - Contralateral leg as a control during skeletal muscle ischemia-reperfusion.
AB  - BACKGROUND: Recent data demonstrated that hind limb ischemia induces skeletal
      muscle mitochondrial dysfunctions. Improvement of such metabolic myopathy
      improves patient's symptomatology, supporting the development of experimental
      models focused on mitochondrial function analysis. However, although the
      nonischemic contralateral leg is often used as a control during unilateral leg
      ischemia, whether it might be useful when assessing ischemia-induced
      mitochondrial dysfunction remains to be investigated. MATERIALS AND METHODS: Both
      ischemic (IR) and nonischemic contralateral legs (CTL) of rats (n=13) submitted
      to 5 h ischemia induced by a rubber band tourniquet applied on the root of the
      hind limb were studied and compared to that of sham-operated animals (SHAM,
      n=13). Maximal oxidative capacities (V(max)) and complexes I, II and IV
      activities of the gastrocnemius mitochondrial respiratory chain were determined,
      using glutamate-malate, succinate (Vs) and TMPD-ascorbate (V(TMPD)) substrates.
      RESULTS: V(max) was decreased in IR (4.6+/-0.4 microM/min/g dry weight) compared
      to both SHAM and CTL muscles (8.5+/-0.5 and 7.1+/-0.4 microM/min/g dry weight, 
      46% and -36%, P<0.001, respectively). V(S) and V(TMPD) were reduced in IR muscle
      (-56% and -48% for V(S); and -25% and -24% for V(TMPD), P<0.001) as compared to
      SHAM and CTL). V(S) and V(TMPD) were similar in SHAM and CTL muscles.
      CONCLUSIONS: Five hours ischemia-reperfusion significantly impaired complexes I,
      II and IV of the ischemic skeletal muscle mitochondrial respiratory chain.
      Interestingly, only V(max) was slightly altered in the contralateral leg,
      supporting that the nonischemic leg might be used as a control when assessing
      mitochondrial function in the experimental setting of unilateral hind limb
      ischemia.

PMID- 19159911
TI  - [B lymphocytes: a new "target" in treatment for multiple sclerosis].

PMID- 19159913
TI  - [Psychiatric assessment in civil law questions].
AB  - Psychiatric reports in German civil law cases are required if questions are
      raised of legal capacity, capacity to express a testamentary will, ability to sue
      or be sued, capacity to marry, ability of mentally disordered patients to consent
      to treatment, and when custody or hospital orders of these patients is considered
      or compensation is due for mental disorders resulting from accidents. Many
      reports must decide whether the ability to decide using sound reason or motives
      is or was impaired by a mental disorder. This capability is attributed to every
      adult person; only if incapability is claimed must it be proven by psychiatric
      assessment. As in most psychiatric court reports, such assessments must be
      structured in several steps. First a clinical diagnosis has to be established
      which must then be translated into legal terminology. After this has been
      accomplished, the psychiatrist must describe the functional impairments caused by
      the disorder and define the probability with which these impairments might affect
      the legal act in question. Most reports are prepared in the context of custody
      law, which centers on helping those patients who, due to a mental disorder,
      cannot manage their own legal matters.

PMID- 19159912
TI  - [Multiple sclerosis and exercise : effects of physical activity on the immune
      system].
AB  - Multiple sclerosis is a chronic inflammatory CNS disease which accounts for
      functional impairment and lasting disability in young adults. Current studies
      demonstrate that physical activity in patients with MS counteracts depression and
      fatigue and may improve quality of life. Interventional studies have described a
      reduction of the functional impairment in MS patients. This report presents
      information on the effects of physical activity on the immune system and the
      release of neurotrophic factors, and highlights current data on a potential
      immunomodulatory effect of exercise in multiple sclerosis.

PMID- 19159914
TI  - [Stroke MRI for risk assessment of intracerebral hemorrhage associated with
      thrombolytic therapy].
AB  - This article summarizes recent developments concerning MRI-based risk assessment
      of symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic
      therapy for acute stroke. Special attention is paid to three imaging parameters:
      cerebral microangiopathy, lesion size on diffusion weighted imaging (DWI), and
      the role of cerebral microbleeds. Both severe cerebral microangiopathy and
      increasing lesion size on DWI are now established risk factors for sICH following
      thrombolysis, while the presence of a single or few microbleeds is not associated
      with a substantially elevated sICH risk.

PMID- 19159915
TI  - [Patient selection for thrombolysis using perfusion and diffusion MRI. An
      overview].
AB  - Multiparametric MRI including diffusion and perfusion imaging provides
      information on the extent of irreversibly damaged ischemic and/or critically
      hypoperfused tissue. Magnetic resonance angiography provides additional
      information on vessel status. The concept of perfusion-diffusion mismatch allows
      the estimation of tissue at risk of infarction which might be salvaged by timely
      reperfusion. In large case series and nonrandomized cohort studies, perfusion
      diffusion mismatch-based thrombolysis was performed not less than 3 h after
      symptom onset with excellent safety and signs of good efficacy. However no
      randomised controlled trial has confirmed this to date. Recent studies improved
      the understanding of the mismatch concept and identified reperfusion
      unequivocally as an important predictor of the clinical response to thrombolysis.
      At the moment MRI-based thrombolysis can be performed after 3 h based on
      individual benefit:risk assessment in experienced stroke centers.

PMID- 19159917
TI  - Association of adiponectin with mortality in older adults: the Health, Aging, and
      Body Composition Study.
AB  - AIMS/HYPOTHESIS: Despite inverse associations with insulin resistance and
      adiposity, adiponectin has been associated with both increased and decreased risk
      of cardiovascular disease. We examined whether adiponectin is associated with
      total and cardiovascular mortality in older adults with well-characterised body
      composition. METHODS: We analysed data from 3,075 well-functioning adults aged 69
      79 years at baseline. Mortality data were obtained over 6.6 +/- 1.6 years. We
      used Cox proportional hazards models adjusting for covariates in stages to
      examine the association between adiponectin and total and cardiovascular
      mortality. RESULTS: There were 679 deaths, 36% of which were from cardiovascular
      disease. Unadjusted levels of adiponectin were not associated with total or
      cardiovascular mortality. However, after adjusting for sex and race, adiponectin
      was associated with an increased risk of both total mortality (hazard ratio 1.26,
      95% CI 1.15-1.37, per SD) and cardiovascular mortality (hazard ratio 1.35, 95% CI
      1.17-1.56, per SD). Further adjustment for study site, smoking, hypertension,
      diabetes, prevalent heart disease, HDL-cholesterol, LDL-cholesterol, renal
      function, fasting insulin, triacylglycerol, BMI, visceral fat, thigh
      intermuscular fat and thigh muscle area did not attenuate this association. This
      association between adiponectin and increased mortality risk did not vary by sex,
      race, body composition, diabetes, prevalent cardiovascular disease, smoking or
      weight loss. CONCLUSIONS/INTERPRETATION: Higher levels of adiponectin were
      associated with increased risks of total and cardiovascular mortality in this
      study of older persons.

PMID- 19159918
TI  - Analyzing the validity of GalR1 and GalR2 antibodies using knockout mice.
AB  - G-protein-coupled receptors (GPCRs) comprise the largest family of cell surface
      receptors and are the major drug targets for the treatment of various human
      diseases. The lack of sensitive and selective antibodies capable of recognizing
      endogenous GPCRs, however, hampers the progress of research on this class of
      receptors. GalR1 through GalR3, GPCRs for the neuropeptide galanin, are potential
      drug targets for seizure, Alzheimer's disease, depression and anxiety, as well as
      pain and metabolic syndrome; therefore, determining the cellular and subcellular
      localization of galanin receptors is of high interest. Several Antibodies raised
      against galanin receptors are currently available from commercial or academic
      sources. We have tested several antibodies to GalR1 and GalR2 on tissues from
      respective knockout mice. Unexpectedly, the immunoreactivity patterns are the
      same in wild-type and in knockout mice, suggesting that current GalR1 and GalR2
      antibodies, under standard immunodetection conditions, might not be suitable for
      mapping the receptors. These findings argue for taking precaution when using
      antibodies to galanin receptors.

PMID- 19159919
TI  - Local administration of sarizotan into the subthalamic nucleus attenuates
      levodopa-induced dyskinesias in 6-OHDA-lesioned rats.
AB  - RATIONALE: Dyskinesia affects the majority of levodopa-treated parkinsonian
      patients within 5-10 years of treatment with levodopa. Clinical and preclinical
      observations suggest that an increase in serotoninergic transmission can
      contribute to the appearance of dyskinesias. It is thus conceivable that a
      modulation of synaptic dopamine (DA) levels induced by the inhibition of
      serotonin (5-HT) release, as a consequence of 5-HT(1A) agonists administration,
      might alleviate dyskinesias. OBJECTIVE: Since 5-HT(1A) receptors are expressed in
      the subthalamic nucleus (STN), the aim of the present study was to assess the
      effect of the intrasubthalamic administration of sarizotan, a compound with full
      5-HT(1A) agonist properties, on levodopa-induced dyskinesias in the 6
      hydroxydopamine (6-OHDA) model of parkinsonism. MATERIALS AND METHODS: Male
      Sprague-Dawley rats received a unilateral 6-OHDA administration in the
      nigrostriatal pathway. A test of apomorphine was performed to evaluate dopamine
      depletion. One week later, a cannula was implanted in the STN. Animals were
      treated with levodopa (6 mg/kg, i.p., twice at day) for 22 consecutive days. On
      day 23, several doses (1 ng, 10 ng, or 1 microg) of sarizotan were administered
      through the cannula to the STN. The higher doses of sarizotan effectively
      attenuated all levodopa-induced dyskinesias including axial, limb, and orolingual
      subtypes. CONCLUSIONS: These results suggest that the STN is a target structure
      for the antidyskinetic action of sarizotan and indicate that drug-mediated
      modulation of STN activity may be an alternative option for the treatment of
      levodopa-induced dyskinesias in Parkinson's disease.

PMID- 19159920
TI  - HPLC-fluorescence detection method for determination of key intermediates of the
      lincomycin biosynthesis in fermentation broth.
AB  - The biosynthetic pathway of the clinically important antibiotic lincomycin is not
      known in details. The precise knowledge of the lincomycin biosynthesis is a
      prerequisite for generation of improved derivatives by means of combinatorial
      genetics. Methods allowing determination of the key intermediates are very
      important tools of the pathway investigation. Two new high-performance liquid
      chromatography methods with fluorescence detection for determination of
      lincomycin precursors in fermentation broth of Streptomyces lincolnensis and its
      lincomycin nonproducing mutants were developed. The first one enables
      simultaneous analysis of methylthiolincosamide (MTL) and N-demethyllincomycin
      (NDL), whereas the second one is suitable for 4-propyl-L-proline (PPL) assay.
      Both methods are based on the pre-column derivatization: MTL and NDL with 4
      chloro-7-nitrobenzofurazan; PPL with o-phthaldialdehyde. The methods were
      validated with lower limit of quantification values of 2.50, 3.75, and 3.75
      microg ml(-1) for MTL, NDL, and PPL, respectively. The inter- and intra-day
      accuracies and precisions were all within 12%. Stability of oxidized and
      derivatized analytes was investigated.

PMID- 19159921
TI  - Multiple spatial representations of number: evidence for co-existing compressive
      and linear scales.
AB  - Although the spatial representation of number (mental number line) is well
      documented, the scaling associated with this representation is less clear.
      Sometimes people appear to rely on compressive scaling, and sometimes on linear
      scaling. Here we provide evidence for both compressive and linear representations
      on the same numerical bisection task, in which adult participants estimate
      (without calculating) the midpoint between two numbers. The same leftward bias
      (pseudoneglect) shown on physical line bisection appears on this task, and was
      previously shown to increase with the magnitude of bisected numbers, consistent
      with compressive scaling (Longo and Lourenco in Neuropsychologia 45:1400-1407,
      2007). In the present study, participants held either small (1-9) or large (101
      109) number primes in memory during bisection. When participants remembered small
      primes, bisection responses were consistent with compressive scaling. However,
      when they remembered large primes, responses were more consistent with linear
      scaling. These results show that compressive and linear representations may be
      accessed flexibly on the same task, depending on the numerical context.

PMID- 19159922
TI  - Signal changes in cortical laminar necrosis-evidence from susceptibility-weighted
      magnetic resonance imaging.
AB  - INTRODUCTION: Two types of infarcts can be identified depending on the
      circumstances leading to its generation-infarcts with pannecrosis and infarcts
      with selective neuronal loss. Cortical laminar necrosis (CLN) can occur due to
      various etiologies of which infarctions and hypoxia are the commonest. Infarction
      results in pannecrosis whereas hypoxia and incomplete infarction result in
      selective neuronal loss with the presence of viable cells, glial proliferations,
      and deposition of paramagnetic substances. We investigated patients with CLN with
      susceptibility-weighted imaging (SWI), a technique highly sensitive to even
      traces of paramagnetic agents or hemorrhagic components. METHODS: We
      retrospectively reviewed medical records of patients diagnosed with CLN as per
      standard criterion. Demographic characteristics and etiologies were recorded.
      Findings in magnetic resonance images including SWI were analyzed. RESULTS: We
      identified 11 patients with CLN, six males and five females with age range of 4
      64 years. Etiologies included hypoxia in two patients and infarction in the nine
      patients. SWI detected diffuse linear hypointensities along the gyral margins in
      CLN due to hypoxic ischemic encephalopathy. Linear dot like hypointensities were
      identified in one patient with infarction. CONCLUSION: CLN due to hypoxic
      ischemic encephalopathy display linear gyral hypointensities and basal ganglia
      hypointensities that are identifiable in SWI and may represent mineralization.
      This might be related to iron transport across the surviving neurons from basal
      ganglia to the cortex, which is not possible in complete infarction. SWI may be
      helpful in understanding the pathophysiological aspects of CLN due to complete
      infarction and hypoxia.

PMID- 19159923
TI  - Coronary artery anomalies and clinically important anatomy in patients with
      congenital heart disease: multislice CT findings.
AB  - In patients with congenital heart disease, coronary artery anomalies are common
      and have different clinical importance from individuals with structurally normal
      hearts. Visibility of the coronary arteries by CT has markedly improved due to
      high temporal resolution and ECG-synchronized data acquisition. In this article
      we describe current multislice CT techniques for coronary artery imaging and
      illustrate coronary artery anomalies and clinically important coronary artery
      anatomy from the point of view of congenital heart disease.

PMID- 19159924
TI  - The DWI 'reversal sign' of white matter hypoxic ischaemic injury in older
      children: an unusual MRI pattern for age.
AB  - We present two children beyond the neonatal and infant age who suffered global
      hypoxic events and showed an MRI appearance of reversal of the diffusion-weighted
      (DWI) and apparent diffusion coefficient (ADC) signal involving exclusively the
      white matter. This is an unusual distribution for this age group and may
      represent delayed postanoxic leukoencephalopathy. The appearance of this type of
      insult has been described as occurring in younger children more frequently than
      in adults. Awareness of this condition, the fact that it may occur earlier, and
      the peculiar and possibly deceptive DWI/ADC signal reversal pattern exclusively
      involving the white matter is critical for making a correct diagnosis and giving
      a prognosis.

PMID- 19159925
TI  - Hydrodynamic properties of cyclodextrin molecules in dilute solutions.
AB  - Three well-known representatives of the cyclodextrin family were completely
      characterized by molecular hydrodynamics methods in three different solvents. For
      the first time the possibility of an estimation of velocity sedimentation
      coefficients s between 0.15 and 0.5 S by the numerical solution of the Lamm
      equation is shown. Comparison of the experimental hydrodynamic characteristics of
      the cyclodextrins with theoretical calculations for toroidal molecules allows an
      estimation of the thickness of the solvent layers on the surface of cyclodextrin
      molecules.

PMID- 19159926
TI  - D-galacturonic acid catabolism in microorganisms and its biotechnological
      relevance.
AB  - D-Galacturonic acid is the main constituent of pectin, a naturally abundant
      compound. Pectin-rich residues accumulate when sugar is extracted from sugar beet
      or juices are produced from citrus fruits. It is a cheap raw material but
      currently mainly used as animal feed. Pectin has the potential to be an important
      raw material for biotechnological conversions to fuels or chemicals. In this
      paper, we review the microbial pathways for the catabolism of D-galacturonic acid
      that would be relevant for the microbial conversion to useful products.

PMID- 19159927
TI  - Substrate specificity of a glucose-6-phosphate isomerase from Pyrococcus furiosus
      for monosaccharides.
AB  - We purified recombinant glucose-6-phosphate isomerase from Pyrococcus furiosus
      using heat treatment and Hi-Trap anion-exchange chromatography with a final
      specific activity of 0.39 U mg(-1). The activity of the glucose-6-phosphate
      isomerase for L: -talose isomerization was optimal at pH 7.0, 95 degrees C, and
      1.5 mM Co(2+). The half-lives of the enzyme at 65 degrees C, 75 degrees C, 85
      degrees C, and 95 degrees C were 170, 41, 19, and 7.9 h, respectively. Glucose-6
      phosphate isomerase catalyzed the interconversion between two different aldoses
      and ketose for all pentoses and hexoses via two isomerization reactions. This
      enzyme has a unique activity order as follows: aldose substrates with hydroxyl
      groups oriented in the same direction at C2, C3, and C4 > C2 and C4 > C2 and C3 >
      C3 and C4. L: -Talose and D: -ribulose exhibited the most preferred substrates
      among the aldoses and ketoses, respectively. L: -Talose was converted to L: 
      tagatose and L: -galactose by glucose-6-phosphate isomerase with 80% and 5%
      conversion yields after about 420 min, respectively, whereas D: -ribulose was
      converted to D: -ribose and D: -arabinose with 53% and 8% conversion yields after
      about 240 min, respectively.

PMID- 19159928
TI  - (68)Ga-labeled cyclic RGD dimers with Gly3 and PEG4 linkers: promising agents for
      tumor integrin alphavbeta3 PET imaging.
AB  - PURPOSE: Radiolabeled cyclic RGD (Arg-Gly-Asp) peptides have great potential for
      the early tumor detection and noninvasive monitoring of tumor metastasis and
      therapeutic response. (18)F-labeled RGD analogs ([(18)F]-AH111585 and
      [(18)F]Galacto-RGD) have been investigated in clinical trials for positron
      emission tomography (PET) imaging of integrin expression in cancer patients. To
      develop new RGD radiotracers with higher tumor accumulation, improved in vivo
      kinetics, easy availability and low cost, we developed two new RGD peptides and
      labeled them with generator-eluted (68)Ga (t(1/2) = 68 min) for PET imaging of
      integrin alpha(v)beta(3) expression in tumor xenograft models. MATERIALS AND
      METHODS: The two new cyclic RGD dimers, E[PEG(4)-c(RGDfK)](2) (P(4)-RGD2, PEG(4)
      = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) and E[Gly(3)-c(RGDfK)](2) (G(3)
      RGD2, G(3) = Gly-Gly-Gly) were designed, synthesized and conjugated with 1,4,7
      triazacyclononanetriacetic acid (NOTA) for (68)Ga labeling. The microPET imaging
      and biodistribution of the (68)Ga labeled RGD tracers were investigated in
      integrin alpha(v)beta(3)-positive tumor xenografts. RESULTS: The new RGD dimers
      with the Gly(3) and PEG(4) linkers showed higher integrin alpha(v)beta(3) binding
      affinity than no-linker RGD dimer (RGD2). NOTA-G(3)-RGD2 and NOTA-P(4)-RGD2 could
      be labeled with (68)Ga within 30 min with higher purity (>98%) and specific
      activity (8.88-11.84 MBq/nmol). Both (68)Ga-NOTA-P(4)-RGD2 and (68)Ga-NOTA-G(3)
      RGD2 exhibited significantly higher tumor uptake and tumor-to-normal tissue
      ratios than (68)Ga-NOTA-RGD2. CONCLUSION: Because of their high affinity, high
      specificity and excellent pharmacokinetic properties, further investigation of
      the two novel RGD dimers for clinical PET imaging of integrin alpha(v)beta(3)
      expression in cancer patients is warranted.

PMID- 19159929
TI  - H. pylori eradication does not reduce paraprotein levels in monoclonal gammopathy
      of unknown significance (MGUS): a prospective cohort study.
AB  - Monoclonal gammopathy of unknown significance (MGUS) is a chronic haematological
      alteration that carries a 1% risk per year of malignant evolution. The origin of
      this disturbance remains unknown. Previous reports have suggested that a subgroup
      of patients presenting MGUS might cure after Helicobacter pylori eradication.
      This study evaluates the effect of H. pylori eradication in a cohort of 30
      patients with MGUS. A 7-day clarithromycin-based triple treatment was prescribed
      to patients with MGUS infected with H. pylori. Quantification of the monoclonal
      component was performed at inclusion and at least 12 months after treatment. The
      monoclonal component persisted unchanged in all patients who cured the H. pylori
      infection.

PMID- 19159930
TI  - Genetic screening for HFE hemochromatosis in 6,020 Danish men: penetrance of
      C282Y, H63D, and S65C variants.
AB  - The aim of this epidemiologic population survey was to assess the penetrance of
      the most frequent hemochromatosis (HFE) gene variants in ethnic Danish men. A
      cohort of 6,020 men aged 30-53 years was screened for HFE C282Y, H63D, and S65C
      variants by restriction fragment length polymorphism analysis. Subsequently, iron
      status markers (serum transferrin saturation, serum ferritin) were analyzed in
      1,452 men. The C282Y allele was present in 5.6%, H63D in 12.8%, and S65C in 1.8%
      of the men. We found 23 out of 6,020 (0.38%) C282Y homozygotes, of whom two had
      been treated with phlebotomy. Among untreated C282Y homozygotes (n = 21) with
      available iron status markers (transferrin saturation n = 18, ferritin n = 16),
      89% had elevated transferrin saturation >or=50%, 94% had elevated ferritin
      >or=300 microg/L, and 88% had elevation of both iron status markers; seven out of
      16 (44%) had ferritin values >800 microg/L. One C282Y homozygote had normal iron
      status markers possibly due to nonexpressivity. Among C282Y/H63D compound
      heterozygotes (n = 66), 23% had elevated transferrin saturation, 27% elevated
      ferritin, and 9% elevation of both iron status markers. Among H63D/H63D
      homozygotes (n = 74), 15% had elevated transferrin saturation, 19% elevated
      ferritin, and 5.4% elevation of both iron status markers. Among C282Y/wild type
      (wt) heterozygotes (n = 255), 9% had elevated transferrin saturation, 9% elevated
      ferritin, and 1.2% elevation of both iron status markers. Among H63D/wt
      heterozygotes (n = 600), 8% had elevated transferrin saturation, 12% elevated
      ferritin, and 2% elevation of both iron status markers. None of the men with the
      S65C variant displayed elevation of both iron status markers. In conclusion, this
      study demonstrates a high penetrance of the C282Y variant in Danish men followed
      by the H63D variant while the S65D variant had no significant impact on iron
      status markers.

PMID- 19159931
TI  - A phase I trial of gemcitabine, docetaxel and carboplatin administered every 2
      weeks as first line treatment in patients with advanced breast cancer.
AB  - OBJECTIVE: To determine the maximum tolerated doses (MTDs) and dose limiting
      toxicities (DLTs) of gemcitabine (GEM), docetaxel (DOC) and carboplatin (CARBO)
      combination. PATIENTS AND METHODS: A total of 33 previously untreated HER-2
      negative patients with stage IIIB-IV breast cancer received escalated doses of
      GEM, DOC and CARBO all given sequentially on day 1 every 2 weeks. Twenty-three
      patients (70%) had previously received adjuvant or neoadjuvant chemotherapy.
      RESULTS: The recommended MTDs are GEM 1,500 mg/m(2), DOC 50 mg/m(2) and CARBO
      3AUC. Seven dose levels were evaluated and neutropenia was the primary dose
      limiting event. Of 319 chemotherapy cycles delivered, grade 3-4 neutropenia
      occurred in 13.5% of them with two cases of febrile neutropenia. Diarrhea and
      asthenia were the most common non-hematological toxicities. Three (16%) complete
      and 6 (32%) partial responses were observed among 19 patients with measurable
      disease. CONCLUSION: The biweekly administration of GEM, DOC and CARBO is a well
      tolerated regimen which merits further evaluation.

PMID- 19159933
TI  - Management of hepatitis B reactivation in patients with lupus nephritis.
AB  - Hepatitis B is endemic in many Asian countries and immunosuppression may
      precipitate hepatitic flare. There is little data on the treatment of hepatitis B
      in patients with systemic lupus erythematosus. We monitored serial transaminase
      and HBV DNA levels in our HBsAg-positive patients with a history of lupus
      nephritis and instituted anti-viral treatment in patients who showed virological
      reactivation. This retrospective pilot study reports the data with this pre
      emptive management strategy. Amongst 228 patients with lupus nephritis, eight
      (3.51%) were HBsAg-positive and five had received Lamivudine treatment for
      hepatitis B. In two patients the virological flares were preceded by lupus flares
      that necessitated an increase in immunosuppressive treatment. Median HBV DNA
      level was 1.9 x 10(7) copies/mL (range 1.2 x 10(4)-1.0 x 10(9) copies/mL) at
      baseline, and it decreased by 2-5 logs after treatment. Four patients had
      abnormal transaminase levels at baseline, with mean alanine aminotransferase at
      125.0 +/- 67.4 U/L, and all achieved normalisation after 3-24 months (median 13
      months) of treatment. Discontinuation of Lamivudine treatment was attempted in
      three patients after 9-15 months. In one patient treatment was recommenced
      because of virological flare. For the remaining two patients in whom treatment
      was not interrupted, one showed sustained viral suppression and one developed
      drug resistance. All antiviral treatments were well-tolerated. These results
      indicate the importance of serial monitoring of HBV DNA and transaminase levels,
      and prompt anti-viral therapy, in the management of HBsAg-positive lupus
      patients. Also, it may be feasible to discontinue treatment in stable patients to
      avoid the selection of drug-resistant variants.

PMID- 19159932
TI  - Potential of alfacalcidol for reducing increased risk of falls and fractures.
AB  - There are no general accepted strategies for combined drug treatments in
      osteoporosis, while in other important chronic diseases combinations of different
      medications are used as a rule to improve therapeutic results and reduce the risk
      of adverse events. It is suggested that the success of combined treatments is
      related to the different modes of action of the respective single therapies. On
      the other hand it was shown that a strong antiresorptive bisphosphonate is able
      to blunt at least in part the effects of anabolic parathyroid hormone peptides
      Calcitriol, the active vitamin D-hormone and its prodrug alfacalcidol lead to
      pleiotropic effects on bone remodelling (antiresorptive, anabolic and enhancing
      mineralization) and in addition to effects on other important target tissues
      (e.g. gut, parathyroid glands, muscle). With active D-analogs significant
      improvements in the therapeutic outcome of osteoporosis can be achieved by the
      resulting improvements of bone quality, calcium absorption and risk reduction of
      falling. The same beneficial effects cannot be achieved with plain vitamin D due
      to feedback controlled, limited renal activation or insufficient conversion in
      the elderly with impairment of renal function. Accordingly alfacalcidol, approved
      as a treatment for different forms of osteoporosis, is besides adoption as a mono
      therapy an interesting candidate for combined therapies. There are interesting
      preclinical trials and clinical pilote studies in the literature proving that a
      parallel therapy with selectively anti-osteoclastic bisphophonates and
      pleiotropically acting D-analogs is able to optimize therapeutic results in
      osteoporosis. In the AAC-Trial (Alfacalcidol-Alendronate-Combined) we studied 90
      patients with established osteoporosis (57 women, 33 men) over two years after
      alternate allocation to three treatment arms (alfacalcidol plus calcium,
      alendronate plus plain vitamin D and Ca, and alendronate plus alfacalcidol and
      Ca). During the 2-year-study we observed the significantly highest lumbar spine
      and hip BMD increases in the combined treatment group (p < 0.001). The number of
      patients with new vertebral and non-vertebral fractures after 2 years was 9 with
      alfacalcidol alone, 10 with alfacalcidol and plain vitamin D and 2 in the group
      receiving alendronate plus alfacalidol (p < 0.02). Furthermore there was a lower
      rate of falls and an earlier reduction in back pain in the patients treated with
      the active combination. This trial confirms the demonstrated highly significant
      advantages of this combined treatment regimen used in the pilote studies.
      Especially in patients with severe osteoporosis this interesting combination of
      two substances with complete different mechanisms of action should be taken into
      consideration.

PMID- 19159934
TI  - Appearance of breast masses on sonoelastography with special focus on the
      diagnosis of fibroadenomas.
AB  - The aim of this study was to show and correlate the imaging features of breast
      masses, especially fibroadenomas, using sonoelastography. Two hundred thirty-five
      patients with 302 breast lesions referred for core needle biopsy participated in
      the study. All lesions appearing as solid masses on conventional US were
      included. Out of the included lesions (270), 115 (42.6%) corresponded to
      histologically confirmed fibroadenomas and 155 (57.4%) to lesions with
      histologically confirmed diagnoses other than fibroadenomas. These were further
      subdivided into fibrocystic changes, lesions with low malignancy potential, and
      malignant lesions. Fibroadenomas were also divided according to histological
      presentation into three subgroups to allow comparative study based on
      elastographic scores. All lesions were classified using a four-point scoring
      system based on ultrasound elastography imaging characteristics. Different
      presentations were observed for elastographic scores according to histological
      presentation of fibroadenomas, whereby fibroadenomas with benign characteristics
      tended to have elastographic classification similar to fibrocystic changes, and
      complex and hypercellular fibroadenomas had classifications similar to harder
      lesions. Fibroadenomas are generally classified as category 3 in the BI-RADS
      lexicon and are the most commonly found lesions in breast biopsies.
      Sonoelastography can provide additional information to conventional studies and
      be used as an auxiliary tool in assessing these masses in clinical practice.

PMID- 19159935
TI  - Accuracy of MRI volume measurements of breast lesions: comparison between
      automated, semiautomated and manual assessment.
AB  - The aim of this study was to investigate the efficacy of a dedicated software
      tool for automated and semiautomated volume measurement in contrast-enhanced (CE)
      magnetic resonance mammography (MRM). Ninety-six breast lesions with
      histopathological workup (27 benign, 69 malignant) were re-evaluated by different
      volume measurement techniques. Volumes of all lesions were extracted
      automatically (AVM) and semiautomatically (SAVM) from CE 3D MRM and compared with
      manual 3D contour segmentation (manual volume measurement, MVM, reference
      measurement technique) and volume estimates based on maximum diameter measurement
      (MDM). Compared with MVM as reference method MDM, AVM and SAVM underestimated
      lesion volumes by 63.8%, 30.9% and 21.5%, respectively, with significantly
      different accuracy for benign (102.4%, 18.4% and 11.4%) and malignant (54.9%,
      33.0% and 23.1%) lesions (p < 0.05). Inter- and intraobserver reproducibility was
      best for AVM (mean difference +/- 2SD, 1.0 +/- 9.7% and 1.8 +/- 12.1%) followed
      by SAVM (4.3 +/- 25.7% and 4.3 +/- 7.9%), MVM (2.3 +/- 38.2% and 8.6 +/- 31.8%)
      and MDM (33.9 +/- 128.4% and 9.3 +/- 55.9%). SAVM is more accurate for volume
      assessment of breast lesions than MDM and AVM. Volume measurement is less
      accurate for malignant than benign lesions.

PMID- 19159936
TI  - Full thickness transanal re-excision following endoscopic removal of malignant
      rectal polyps.
AB  - PURPOSE: Segmental resection is recommended for malignant polyps of the colon
      that are removed endoscopically with questionable margins. However, when such a
      lesion is present in the rectum, radical resection may involve a higher risk
      procedure such as low anterior resection or abdominoperineal resection. We report
      our long-term results in patients treated by transanal re-excision (TAR)
      following endoscopic removal of malignant rectal polyps (MRP). METHODS: Twenty
      three patients were identified between 2000 and 2006 as having undergone TAR
      following complete gross endoscopic removal of an MRP. All lesions demonstrated
      close, unclear, or microscopically positive polypectomy margins. RESULTS: Our
      population consisted of 13 men and 10 women with a median age of 61 years (range
      52-86). Seventeen (74%) patients demonstrated no evidence of residual tumor. Six
      patients were found to have residual disease (three adenoma, two adenocarcinoma,
      one positive lymph node). Morbidity was minimal, and there were no mortalities.
      At a median follow-up of 64.6 months (range 11-90), there have been no
      recurrences. CONCLUSION: We conclude that in approximately one quarter of
      patients, residual disease is identified following TAR. Given the relatively
      safety and the low recurrence rate associated with this procedure, TAR may be
      considered as an alternative to radical resection for MRPs with unsatisfactory
      margins.

PMID- 19159937
TI  - [Drug therapy during pregnancy and breast feeding. Updated summary].

PMID- 19159938
TI  - [Leflunomide in combination with TNF-blockers for Methotrexate intolerance].

PMID- 19159939
TI  - [Clinical and serological findings of giant-cell arteritis].
AB  - Giant cell arteritis (GCA) frequently appears as cranial arteritis (eg. temporal
      arteritis) with headache, pain on chewing and visual disturbances. In addition,
      extracranial manifestations are often observed leading to aneurysmatic
      dilatations and dissections of the aorta as well as stenoses of large thoracic,
      abdominal or limb arteries. The vascular signs are accompanied by general disease
      symptoms, e.g. malaise, elevated temperatures, weight loss and depression.
      Polymyalgia rheumatica (PMR) is the most frequent rheumatic manifestation of GCA
      but also occurs independently from GCA. The structural correlate for the PMR
      symptoms is first and foremost extra-articular inflammation (tenosynovitis,
      bursitis) of large joints and the vertebral column (interspinal bursitis). In
      addition, vasculitis of large arteries in PMR must be considered particularly in
      the presence of high inflammatory activity. While specific laboratory markers for
      GCA and PMR are lacking elevated values for the erythrocyte sedimentation rate
      and C-reactive protein are present in almost all patients at disease onset.
      Besides the clinical evaluation, the serological acute phase reaction represents
      the main parameter for the course during therapy of this relatively frequent
      disease in elderly people.

PMID- 19159940
TI  - Nasopharyngeal carcinoma in adolescents: a retrospective review of 42 patients.
AB  - The aim of the present study was to evaluate the characteristics and outcome of
      adolescent patients with nasopharyngeal carcinoma (NPC) disease. The study
      concerned 46 pediatric NPC patients treated during the period 1999-2002 at the
      National Institute of Oncology, Rabat. The median age of the patients was 16
      years. The male/female ratio was 2.8/1. Histologically, all patients had
      undifferentiated carcinoma. A total of 93% presented nodal metastasis. Four (9%)
      had distant metastasis. All patients received neoadjuvant multiagent chemotherapy
      containing cisplatin, followed by radiotherapy. Kaplan-Meier curves were used to
      evaluate prognostic factors. The log-rank test was used to evaluate the
      differences between the groups. While none of the patients had locoregional
      failure, nine patients (29%) developed distant metastasis. The disease-free
      survival and overall survival (OS) rate for the entire group were 73 and 41%,
      respectively. Responders to chemotherapy had superior OS (P < 0.001). We suggest
      that combined modality management using multi-agent chemotherapy and RT as an
      effective treatment of NPC disease which will achieve satisfactory locoregional
      control and OS of NPC pediatric patients. Response to chemotherapy was an
      important prognostic factor.

PMID- 19159941
TI  - Application methods of local anaesthetic infiltrations for postoperative pain
      relief in tonsillectomy: a prospective, randomised, double-blind, clinical trial.
AB  - Perioperative local anaesthetics are often used to reduce the postoperative pain
      in tonsillectomy. There exist three different ways of applying local
      anaesthetics: (1) pre-incisional peritonsillar; (2) post-tonsillectomy wound
      infiltration; (3) post-tonsillectomy packing with soaked gauze. The objective of
      the study is the evaluation of differences of pain reduction comparing the three
      different techniques of application. The study design mainly includes intra
      individual, prospective and double-blinded. One hundred and eighty patients (3-45
      years) with recurrent tonsillitis were included. The charts of 156 were eligible
      for analysis. Bupivacaine was applied on both sides randomized in different ways.
      Pain on each side was registered for 6 days on the ward by a blinded nurse. When
      directly compared with the other two application methods, the post-tonsillectomy
      injection of bupivacaine provides significantly better results during the
      monitored time period. Postoperative bleeding was observed in 11 (7.3%) cases
      without any correlation to an application procedure. No other adverse effects
      were observed. In conclusion, post-tonsillectomy infiltration of the wounds with
      bupivacaine is superior to pre-incisional infiltration technique as well as post
      tonsillectomy packing of the wounds with 0.5% bupivacaine-soaked gauze swab.

PMID- 19159942
TI  - Tympanoplasty in children.
AB  - Closure of uncomplicated tympanic membrane perforation (tympanoplasty) is usually
      a straightforward procedure with a good success rate. Many studies report a
      success rate from 60 to 99% in adults, whereas a 35-94% success rate in children.
      The definition of successful tympanoplasty varies from one author to other. Some
      authors report that an intact tympanic membrane considered a successful surgical
      result, whereas the other authors may also consider the postoperative hearing, as
      well as middle ear aeration, as a part of good outcome. This review is an insight
      into the recent and as well as the past literature on prognostic factors in
      pediatric tympanoplasty. This article reports an overview of the commonly
      reported factors which are thought to affect the tympanoplasty in children. Age
      is considered as one of the most important factor determining the successful
      outcome of tympanoplasty. Most of the studies did not reveal any significant
      difference in result between pediatric tympanoplasty from those of adult ones.
      Interestingly, in one study; it was found that patients younger than 16 years had
      decreased graft uptake compared with adults. However, in this same study; it was
      found that the younger patients had better postoperative hearing with better
      postoperative AB gap closure. The other factors which seem to influence the
      success rate of tympanoplasty are the size of perforation, technique used,
      presence or absence of otorrhoea, eustachian tube function and status of the
      contralateral ear. A study has revealed that posterior perforation had poorer
      results but it may be a distorted finding as the surgical method was not
      controlled. Regarding the size of perforation and its influence on the success
      rate of tympanoplasty, there is again difference of opinion. In one study, it was
      found that perforations greater than 50% had poorer results, but other studies
      contradict this statement stating that the success of tympanoplasty has no
      bearing with the size of perforation. Poor eustachian tube function has been
      offered as an explanation by some authors as younger age may be correlated with
      lower tympanoplasty success rates, but some authors refute this by stating that
      poor eustachian tube function not necessarily an indicator of poor surgical
      outcome. In conclusion, the success of tympanoplasty in children, with little
      doubt, depends on a number of factors. The past and recent literature has not
      produced a consensus of convincing evidence supporting any one parameter.

PMID- 19159943
TI  - The German case-control scene investigation study on SIDS: epidemiological
      approach and main results.
AB  - The present study, which was part of the German SIDS Study (GeSID), enrolled
      sudden infant death syndrome (SIDS) cases and population controls and obtained
      objective scene data via specifically trained observers shortly after discovery
      of each dead infant. Infants who had died suddenly and unexpectedly at ages
      between 8 and 365 days were enrolled in five regions of Germany between November
      1998 and October 2001. Shortly after discovery of each dead infant, a specially
      trained doctor of legal medicine visited the bereaved family at home. Data were
      obtained by measurements and observations. Dead infants underwent a standardised
      autopsy, additional information being obtained by standardised parent interviews.
      Investigation of the sleep environment and wake-up scene in matched controls
      followed the same protocol. A total of 52 SIDS cases and 154 controls were
      enrolled, 58% were boys, and median age of cases vs. controls was 126 vs. 129
      days. Risk factors in the sleeping environment were pillow use (adjusted OR 4.3;
      95%CI 1.6-11.6), heavy duvets (OR 4.4; 1.5-13.3), soft underlay (OR 3.0; 1.1
      8.7), face covered by bedding (OR 15.8; 2.5-102.1) and entire body covered by
      bedding (OR 35.5; 5.5-228.3). Using a standardised protocol, including objective
      measurements of the sleep environment and a case-control design, this study was
      able to confirm many risk factors for SIDS.

PMID- 19159944
TI  - Does enzyme replacement therapy influence the ocular changes in type VI
      mucopolysaccharidosis?
AB  - BACKGROUND: To describe the ocular changes noted in seven patients with type VI
      mucopolysaccharidosis (MPS VI) during 44 months of follow-up while on enzyme
      replacement therapy (ERT). METHODS: One male and six female patients with MPS VI
      were followed-up for a mean period of 44 months while undergoing enzyme
      replacement therapy (ERT) with recombinant arylsulfatase B (Naglazyme). They were
      examined annually for visual acuity, corneal clouding, intraocular pressure
      (IOP), optic nerve head and fundus morphology. Corneal clouding was documented by
      photography. We acknowledge that our methodology may not have been sensitive
      enough to detect extremely mild ocular changes, including minimal increases in
      corneal thickness or clouding. Nevertheless, this limitation has been considered
      in the interpretation of our findings. RESULTS: Ophthalmological findings
      remained stable in 5/7 patients. One patient experienced a modest improvement in
      visual acuity of more than 2 Snellen lines in one eye, while another patient
      suffered a deterioration in visual acuity of more than 2 Snellen lines in both
      eyes. Five out of seven patients showed optic nerve pathology: two of these
      exhibited optic nerve head swelling, while the other three showed variable
      degrees of optic nerve atrophy. All seven patients suffered from the typical
      corneal stromal opacities, however, to variable extents. CONCLUSION: Visual
      function and ocular findings did not deteriorate in six out of seven MPS VI
      patients during a mean follow-up period of 3 and a half years on ERT.

PMID- 19159945
TI  - Progressive renal dysfunction and macrophage infiltration in interstitial
      fibrosis in an adenine-induced tubulointerstitial nephritis mouse model.
AB  - Adenine phosphoribosyltransferase deficiency in mice or an excessive oral intake
      of adenine leads to the accumulation of 2,8-dihydroxyadenine (DHA) in renal
      tubules and that causes progressive renal dysfunction accompanied by interstitial
      fibrosis. However, the precise mechanism responsible for DHA-induced progressive
      fibrosis is not fully understood. The present study investigates the possible
      involvement of monocytes/macrophages in the progressive fibrosis induced by
      feeding adenine to mice. Urinary calculi were deposited in tubules on day 7 after
      the initiation of adenine feeding. Elevation of the serum creatinine level and
      loss of body weight were observed in a time-dependent manner, suggesting the
      development of typical renal dysfunction induced by the adenine feeding. In renal
      tissue, mRNA expression of MCP-1, MIP-1alpha, RANTES, IL-1beta, CCR2, TGF-beta,
      alpha-smooth muscle actin (alpha-SMA) and collagen 1a1 was increased in parallel.
      Along with the increased expression of these genes, a remarkable infiltration of
      macrophages into the tubulointerstitial area was observed in a time-dependent
      manner. In addition, in the tubulointerstitial area, alpha-SMA positive
      fibroblasts were increased in parallel with collagen deposition. These results
      suggest that the excessive consumption of adenine leads to progressive renal
      dysfunction in mice. We speculate that the accumulation of DHA in tubules might
      stimulate epithelium to produce MCP-1 and that profibrogenic TGF-beta produced by
      infiltrated macrophages might stimulate interstitial fibroblasts to produce
      collagen. These results indicate that macrophage infiltration is one of the
      triggers that initiates interstitial fibroblast activation and collagen
      deposition followed by renal dysfunction.

PMID- 19159947
TI  - Changes in glucose tolerance and insulin sensitivity following 2 weeks of daily
      cinnamon ingestion in healthy humans.
AB  - Cinnamon can improve fasting glucose in humans yet data on insulin sensitivity
      are limited and controversial. Eight male volunteers (aged 25 +/- 1 years, body
      mass 76.5 +/- 3.0 kg, BMI 24.0 +/- 0.7 kg m(-2); mean +/- SEM) underwent two 14
      day interventions involving cinnamon or placebo supplementation (3 g day(-1)).
      Placebo supplementation was continued for 5 days following this 14 day period.
      Oral glucose tolerance tests (OGTT) were performed on days 0, 1, 14, 16, 18, and
      20. Cinnamon ingestion reduced the glucose response to OGTT on day 1 (-13.1 +/-
      6.3% vs. day 0; P < 0.05) and day 14 (-5.5 +/- 8.1% vs. day 0; P = 0.09).
      Cinnamon ingestion also reduced insulin responses to OGTT on day 14 (-27.1 +/-
      6.2% vs. day 0; P < 0.05), as well as improving insulin sensitivity on day 14
      (vs. day 0; P < 0.05). These effects were lost following cessation of cinnamon
      feeding. Cinnamon may improve glycaemic control and insulin sensitivity, but the
      effects are quickly reversed.

PMID- 19159946
TI  - Effect of a 20-day ski trek on fuel selection during prolonged exercise at low
      workload with ingestion of 13C-glucose.
AB  - Fuel selection was measured in five subjects (36.0 +/- 10.5 years old; 87.3 +/-
      12.5 kg; mean +/- SD) during a 120-min tethered walking with ski poles (1.12 l
      O(2) min(-1)) with ingestion of (13)C-glucose (1.5 g kg(-1)), before and after a
      20-day 415-km ski trek [physical activity level (PAL) approximately 3], using
      respiratory calorimetry, urea excretion, and (13)C/(12)C in expired CO(2) and in
      plasma glucose. Before the ski trek, protein oxidation contributed 9.7 +/- 1.6%
      to the energy yield (%En) while fat and carbohydrate (CHO) oxidation provided
      73.5 +/- 5.5 and 16.7 +/- 6.5%En. Plasma glucose was the main source of CHO (52.9
      +/- 9.5%En) with similar contributions from exogenous glucose (27.2 +/- 3.1%En),
      glucose from the liver (25.6 +/- 8.3%En) and muscle glycogen (20.9 +/- 4.0%En).
      Endogenous CHO contributed 46.6 +/- 3.9%En. Following the ski trek %En from
      protein, fat, CHO, exogenous glucose and endogenous CHO were not significantly
      modified (10.1 +/- 1.3, 15.8 +/- 6.7, 74.1 +/- 6.5, 28.7 +/- 3.0 and 45.5 +/-
      7.5%En, respectively) but the %En from plasma glucose and glucose from the liver
      (41.1 +/- 3.6 and 12.4 +/- 4.0%En) were reduced, while that from muscle glycogen
      increased (33.0 +/- 4.5%En). These results show that in subjects in the fed state
      with glucose ingestion during exercise, CHO is the main substrate oxidized, with
      major contributions from both exogenous and endogenous CHO. Following a ~3-week
      period of prolonged low intensity exercise, the %En from protein, fat, CHO,
      exogenous glucose and endogenous CHO were not modified. However, the %En from
      glucose released from the liver was reduced (possibly due to an increased insulin
      sensitivity of the liver) while that from muscle glycogen was increased.

PMID- 19159948
TI  - Salivary cortisol in top-level professional soccer players.
AB  - We have tested the hypothesis that salivary cortisol increases after a
      competitive training match in top-level male professional soccer players divided
      in team A (n = 11) versus team B (n = 11). Saliva samples collected before and
      after the match were analyzed. Salivary cortisol concentrations were measured by
      enzyme-linked immunosorbent assay. The results from a two-way ANOVA with repeated
      measures showed no significant changes in salivary cortisol between either teams
      or time points (P > 0.05). Further investigation regarding competitive matches in
      a competition environment is warranted. In summary, the influence of intensive
      competitive training match alone appears to be minimal on salivary cortisol
      changes in top-level soccer adapted to this type of stress. From a practical
      application, the variability of the responses among the players leads us to
      suggest that there is a need to individually analyse the results with team
      sports.

PMID- 19159949
TI  - Differences in comfort perception in relation to local and whole body skin
      wettedness.
AB  - Relevance of local skin wettedness (w (local)) to general thermal comfort while
      wearing clothing was investigated in eight males. In the experiments, skin
      wettedness of the whole body (w (body)) was controlled to be around the thermal
      comfort limit, while w (local) in different target locations of equal area
      (anterior and dorsal torso, arms, and thighs) was pushed beyond the comfort limit
      using special test garments. Subjects walked on a treadmill at 4.5 km h(-1) under
      22 degrees C 50% RH. Arms and thighs were thermally in discomfort when their w
      (local) exceeded 0.32. On the other hand, discomfort in the anterior and dorsal
      torso was initiated when their w (local) arrived at 0.42 and 0.45. That is, the
      relation of the local comfort limit with w (local) differed depending upon the
      location. It was observed; however, that general discomfort was not induced when
      w (body) remained below 0.36 even if w (local) was higher than its local comfort
      limit.

PMID- 19159950
TI  - Differential load impact upon arm tremor dynamics and coordinative strategy
      between postural holding and position tracking.
AB  - This study contrasted the effects of load characteristics on coordinative
      strategies between postural holding and position tracking. Fifteen healthy adults
      conducted postural holding and sinusoidal tracking with the index finger while
      manipulated loads (0, 50, and 100 g) were superimposed on an outstretched arm.
      Oscillatory activities in the upper limb, target curve, and index position were
      monitored. The results showed that the effect of loading upon tremor structure
      was segment-dependent in relation to the task being performed. Load addition
      resulted in a task-dependent compensatory modulation of tremors between the
      distal segments (hand and finger), despite tremor augmentation in the proximal
      segments (forearm or arm). In comparison with postural holding, manual tracking
      exhibited a greater release of tremor coupling in the finger-hand complex, but a
      stronger tremor coupling in the forearm-arm complex secondary to added mass.
      Tremor reorganization in the upper limb following load addition could be
      characterized by changes in the primary principal component of segment tremors,
      which was more downward modulated during loaded tracking than loaded holding.
      Functionally, adding weight reduced tremor-relevant tracking error, while an
      opposing load did not add to holding steadiness. In summary, tremors associated
      with loaded holding and tracking were differently reorganized, in support of the
      hypothesis that coordination strategies against destabilizing loads for postural
      task and movement task are fundamentally dissimilar.

PMID- 19159952
TI  - Primary mesh augmentation with fibrin glue for abdominal wall closure-
      investigations on a biomechanical model.
AB  - BACKGROUND: The occurrence of incisional hernias after various types of abdominal
      procedures and incisions continues to be a problem. A number of studies conducted
      for diverse risk groups have identified a beneficial role for the prophylactic
      use of mesh augmentation. To what extent this affects the stability of a suture
      was tested in our biomechanical model. MATERIALS AND METHODS: To that effect, we
      compared three groups, carrying out six measurements in each case: (1) single
      suture in a muscle specimen, (2) suture and additional reinforcement with fibrin
      glue, and (3) suture and additional reinforcement with a mesh fixed with fibrin
      glue (Tissucol, Tisseel; with an overlap of 2 cm to all sides). RESULTS: The
      single suture conferred a tensile strength, which in our model, was just above
      the prescribed maximum abdominal pressure of 32 N (37.3 N). The additional use of
      fibrin glue did not have any significant impact on this result (41.8 N). Only
      through mesh augmentation with fibrin glue was it possible to achieve a
      significantly greater tensile strength (64.5 N, p = 0.003). CONCLUSIONS: The
      prophylactic use of meshes for stabilization of laparotomy closures appears to be
      effective. Adequate mesh fixation can be achieved with fibrin glue alone. Further
      experimental studies and in particular randomized clinical trials are needed to
      demonstrate proof of the long-term advantages of mesh augmentation in risk
      groups.

PMID- 19159951
TI  - Malignant fibrous histiocytoma--pleomorphic sarcoma, NOS gene expression,
      histology, and clinical course. A pilot study.
AB  - PURPOSE: The new classification of malignant fibrous histiocytoma leaves only a
      small group of tumors without further line of differentiation, so-called
      pleomorphic sarcomas, not otherwise specified (NOS) as a pseudo-entity. This
      study focused on these tumors and analyzed the association of gene expression
      profiles to clinical outcome. MATERIALS AND METHODS: Ten fresh samples of
      pleomorphic NOS sarcomas were evaluated histopathologically and by means of
      microarray analysis. Analysis of expression profiles was performed by clustering
      methods as well as by statistical analysis of primary vs recurrent tumors,
      irradiated vs nonirradiated tumors, tumors of patients above and below 60 years
      of age, male and female, and of tumors that developed metastatic or recurrent
      disease during the clinical course and those that did not. RESULTS: Tumor
      clustering did not correlate to any histopathological or clinical finding.
      Detailed gene expression analysis showed a variety of genes whose upregulation
      (platelet-derived growth factor receptor alpha polypeptide, solute carrier family
      39 member 14, solute carrier family 2 member 3, pleiotrophin, trophinin,
      pleckstrin and Sec7 domain containing 3, enolase 2, biglycan, SH3 and cysteine
      rich domain, matrix metalloproteinases 16) and whose downregulation (tissue
      inhibitor of metalloproteinase 4, hairy/enhancer of split related with YRPW motif
      2, protein tyrosine phosphatase receptor-type Z polypeptide 1, SH3 domain GRB2
      like 2, microtubule-associated protein 7, potassium voltage-gated channel shaker
      related subfamily member 1, RUN and FYVE domain containing 3, Sin3A-associated
      protein 18 kDa, proline-rich 4, calcium/calmodulin-dependent protein kinase ID,
      myeloid/lymphoid or mixed-lineage leukemia translocated to 3, insulin-like growth
      factor binding protein 5, nucleoside diphosphate-linked moiety X-type motif 9,
      NudC domain containing 3, imprinted in Prader-Willi syndrome, TAF6-like RNA
      polymerase II p300/CBP-associated factor 65 kDa, WD repeat and SOCS box
      containing 2, adenosine diphosphate ribosylation factor 3, KRR1, proliferation
      associated 2G4; CD36, complement component (3b/4b) receptor 1, solute carrier
      family 4 sodium bicarbonate cotransporter member 4, lipoprotein lipase (LPL),
      GATA binding protein 3, LPL, glutathione peroxidase 3, D: -aspartate oxidase,
      apolipoprotein E, sphingomyelin phosphodiesterase acid-like 3A) were associated
      with poor clinical outcome in terms of development of metastatic or recurrent
      disease. CONCLUSIONS: The classification of these tumors may undergo further
      changes in the future. Gene expression profiling can provide additional
      information to categorize pleomorphic sarcoma (NOS) and reveal potential
      prognostic factors in this "entity."

PMID- 19159953
TI  - Risk factors for Kawasaki disease-associated coronary abnormalities differ
      depending on age.
AB  - INTRODUCTION: The clinical manifestations and risk factors for developing
      coronary artery abnormalities (CAA) in Kawasaki disease (KD) might differ
      depending on age. MATERIALS AND METHODS: From January 2001 to July 2007, 161
      patients with an age younger than 1 year (younger group) and 60 patients with an
      age older than 5 years (older group) were diagnosed with KD at the Korea
      University Medical Center. Their medical records were reviewed retrospectively
      and the two groups were compared in terms of a number of variables commonly
      associated with the development of CAA, including clinical manifestations and
      laboratory findings. RESULTS: While the overall incidence of KD-associated CAA in
      our hospital was 6.7%, CAA developed in 20 (12.4%) of the younger group and ten
      (16.7%) of the older group, respectively. The CAA (+) cases of the younger group
      had a longer duration of total fever (9.1 +/- 3.3 vs 6.3 +/- 1.9 days, p = 0.002)
      and showed fewer diagnostic symptoms (3.0 +/- 1.2 vs 4.3 +/- 1.1, p < 0.001) than
      the CAA (-) cases. The CAA (+) cases of the older group had a longer duration of
      total fever (14.1 +/- 10.4 vs 6.5 +/- 1.9 days, p = 0.045), especially with
      respect to post-intravenous gamma globulin (IVGG) fever (7.9 +/- 9.6 vs 1.1 +/-
      0.8 days, p = 0.052), and had higher total white blood cell counts, erythrocyte
      sedimentation rates, C-reactive protein levels, total bilirubin levels, and
      Harada scores and lower serum albumin and sodium levels than the CAA (-) cases.
      Multivariable logistic regression analysis revealed that the factors that were
      associated significantly with the development of CAA were the number of total
      symptoms (OR = 0.494, 95% confidence interval (CI) = 0.281-0.871, p = 0.015) in
      the younger group and the duration of post-IVGG fever (OR = 1.958, 95% CI = 1.098
      3.492, p = 0.023) and the Harada score (OR = 3.455, 95% CI = 1.012-11.796, p =
      0.048) in the older group. CONCLUSION: Incomplete clinical manifestations in the
      younger group and IVGG nonresponsiveness in the older group are associated with
      the development of KD-associated CAA. These age-specific characteristics could
      aid the customization of the diagnostic and therapeutic strategies of KD, thereby
      helping to improve the outcome of this disease.

PMID- 19159954
TI  - Burden of otitis media and pneumonia in children up to 6 years of age: results of
      the LISA birth cohort.
AB  - Infections play an important role in childhood. For Germany, few data are
      available on the epidemiology of infectious diseases such as otitis media and
      pneumonia in children. We therefore described the prevalence, first episode
      proportions and recurrence of these childhood infection diseases in selected
      regions of Germany in children up to 6 years of age. The analysis was based on
      data from the LISA Study, a prospective population-based birth cohort study
      including 3,097 full-term infants. Information was collected by parent
      questionnaire. The first episode proportions for the first 6 years of life were
      high for otitis media (66.7%; 95%CI 0.65-0.69) and pneumonia (13.5%; 95%CI 0.12
      0.15). The annual first episode proportions for otitis media ranged from 7.3% to
      25.6% and for pneumonia from 1.4% to 3.4%; both peaked during the second year.
      The average number of otitis media episodes was 2.2 (SD 2.0) episodes per child
      within the first 2 years. During the first 2 years of life, hospitalisations due
      to otitis and pneumonia occurred in up to 7.8 per thousand and 3.0 per thousand
      of the children, respectively. On average, 50.6% of the children with otitis
      media were treated with antibiotics during the first year of life. In conclusion,
      this analysis shows that infectious diseases, especially otitis media, are very
      frequent childhood diseases in Germany. Thus, parents and physicians should not
      per se worry about a high frequency of otitis media during early childhood.

PMID- 19159955
TI  - Sarcoptes mite from collection to DNA extraction: the lost realm of the neglected
      parasite.
AB  - Sarcoptes mite from collection to DNA extraction forms the cornerstone for
      studies on Sarcoptes scabiei. Whilst the new science era took a shy leap into the
      different facets of mite studies, the cornerstone was almost entirely neglected.
      Mite collection, cleaning, storage and DNA extraction were, basically, humble
      attempts to extrapolate, adapt, modify or 'pirate' those existing methods to the
      peculiarities of Sarcoptes research. These aspects usually constituted few lines,
      bashfully mentioned, in the materials and methods section of some papers, which
      arose in unique problems concerning cost-effectiveness, time profitability,
      safety and even worse, the credibility of the results, creating contradictory
      conclusions in some cases. This 'noisy' situation encouraged us to collect,
      classify and review, for the first time to our knowledge, some aspects relating
      to studies on Sarcoptes mite from collection to DNA extraction, which will be
      useful for further studies on Sarcoptes, and have implications for the effective
      control of the diseases Sarcoptes mite causes. Further studies are needed,
      especially to compare the profitability, safety, sensibility and specificity of
      the different methods of this neglected realm of the ubiquitous ectoparasite.

PMID- 19159956
TI  - Expression and biochemical characterization of the Plasmodium falciparum protein
      kinase A catalytic subunit.
AB  - Dissemination of drug-resistant malaria parasites represents one of the most
      important public health problems; therefore, the development of new antimalarial
      compounds is required. Cyclic AMP-dependent protein kinase is implicated in
      numerous cellular processes and an essential role for this enzyme has also been
      reported in the intraerythrocytic growth of the malaria parasite. The cAMP
      dependent protein kinase from Plasmodium falciparum (PfPKA) plays an important
      role in the parasite life cycle and represents an attractive target for the
      development of antimalarial drugs. In this work, a recombinant PfPKA catalytic
      subunit (PfPKAc) was over-expressed in Escherichia coli and successfully purified
      using a two-step chromatographic process. The enzymatic properties of the
      recombinant PfPKAc were then determined using a sensitive fluorogenic assay
      suitable for biochemical characterization and inhibitor screening. This work
      provides new insights on the study of PfPKAc that will contribute to future
      investigations of the parasite cAMP signaling pathway and to high-throughput
      screening of specific malarial PKA inhibitors.

PMID- 19159957
TI  - Growth hormone treatment started in the first year of life in infants with
      chronic renal failure.
AB  - Infants with chronic renal failure (CRF) are at high risk of experiencing severe
      growth retardation. We report a study of 12 infants with CRF who have been
      treated with recombinant human growth hormone (rhGH) since the age of 0.5 +/- 0.3
      years. A control group comprised 15 infants with less severe CRF who were being
      treated during the same period, but who did not receive rhGH. Despite the infants
      in the rhGH group had more severe renal failure, they grew at least as well as
      those in the control group and experienced catch-up growth that started earlier
      and was more sustained; they also gained more weight. Between the age of 0.5 and
      2.5 years, the height standard deviation score (HtSDS) improved from -2.0 +/- 1.2
      to -0.9 +/- 0.9 in the rhGH group (p < 0.005) and from -1.6 +/- 1.6 to -1.0 +/-
      1.9 in the control group (p=non significant, n.s.). The average gain in HtSDS was
      +1.1 +/- 0.8 in the treated group and +0.6 +/- 1.4 in the control group (p =
      n.s.). During the same period, the weight SDS improved from -2.2 +/- 0.9 to -0.6
      +/- 1.2 (p < 0.005) and from -1.9 +/- 1.2 to -1.3 +/- 1.2 (p=n.s.) in the
      treatment and control groups, respectively. Nutritional intake was similar in
      both groups, while parathyroid hormone levels tended to increase, although not
      significantly, after rhGH treatment (p=n.s.). The results of this pilot study
      suggest that very early treatment with rhGH in patients with early-onset CRF may
      improve growth.

PMID- 19159958
TI  - Effects of selenium on the structure and function of recombinant human S-adenosyl
      L-methionine dependent arsenic (+3 oxidation state) methyltransferase in E. coli.
AB  - The effects of Se(IV) on the structure and function of recombinant human arsenic
      (+3 oxidation state) methyltransferase (AS3MT) purified from the cytoplasm of
      Escherichia coli were studied. The coding region of human AS3MT complementary DNA
      was amplified from total RNA extracted from HepG2 cell by reverse transcription
      PCR. Soluble and active human AS3MT was expressed in the E. coli with a Trx
      fusion tag under a lower induction temperature of 25 degrees C. Spectra (UV-vis,
      circular dichroism, and fluorescence) were first used to probe the interaction of
      Se(IV) and recombinant human AS3MT and the structure-function relationship of the
      enzyme. The recombinant human AS3MT had a secondary structure of 29.0% alpha
      helix, 23.9% beta-pleated sheet, 17.9% beta-turn, and 29.2% random coil. When
      Se(IV) was added, the content of the alpha-helix did not change, but that of the
      beta-pleated sheet increased remarkably in the conformation of recombinant human
      AS3MT. Se(IV) inhibited the enzymatic methylation of inorganic As(III) in a
      concentration-dependent manner. The IC(50) value for Se(IV) was 2.38 muM. Double
      reciprocal (1/V vs. 1/[inorganic As(III)]) plots showed Se(IV) to be a
      noncompetitive inhibitor of the methylation of inorganic As(III) by recombinant
      human AS3MT with a K (i) value of 2.61 muM. We hypothesized that Se(IV) interacts
      with the sulfhydryl group of cysteine(s) in the structural residues rather than
      the cysteines of the active site (Cys156 and Cys206). When Se(IV) was combined
      with cysteine(s) in the structural residues, the conformation of recombinant
      human AS3MT changed and the enzymatic activity decreased. Considering the
      quenching of tryptophan fluorescence, Cys72 and/or Cys226 are deduced to be
      primary targets for Se(IV).

PMID- 19159959
TI  - Cerebral ischemia owing to compression of the brain by swollen temporal muscle
      used for encephalo-myo-synangiosis in moyamoya disease.
AB  - Compression of the brain by swollen temporal muscle used for indirect pial
      synangiosis is a rare complication after the revascularization surgery for
      moyamoya disease, and its mechanism and clinical presentation are undetermined. A
      26-year-old woman, who had been suffering transient ischemic attack (TIA),
      underwent superficial temporal artery-middle cerebral artery anastomosis with
      encephalo-myo-synangiosis (EMS) on the affected hemisphere. The (123)I-IMP-SPECT
      1 day after surgery demonstrated an improvement of cerebral blood flow (CBF) on
      the operated hemisphere. Two days later, however, she suffered fluctuating
      aphasia when computed tomography scan revealed marked swelling of the temporal
      muscle used for EMS. The (123)I-IMP-SPECT 4 days after surgery showed significant
      decrease in CBF by the compression of the brain. Then, we performed revision of
      EMS. The base of the temporal muscle was markedly compressed by the edge of the
      free bone flap, which resulted in swelling of the entire temporal muscle used for
      EMS. We drilled out the edge of the free bone flap for decompression. Her aphasia
      disappeared postoperatively, and CBF normalized 7 days after the initial surgery.
      Her TIA disappeared, and there was no deterioration during the follow-up period.
      The STA-MCA bypass has been patent since the initial surgery. Surgical
      revascularization including EMS has a substantial risk for cerebral ischemia
      owing to compression of the brain by temporal muscle swelling. Relative wide bone
      window for temporal muscle insertion is necessary to avoid this rare
      complication. Once the flow compromise is confirmed, we recommend early
      decompression by the revision of EMS.

PMID- 19159960
TI  - Environmental and socioeconomic assessment of impacts by mining activities-a case
      study in the Certej River catchment, Western Carpathians, Romania.
AB  - BACKGROUND, AIM AND SCOPE: In the region of the Apuseni Mountains, part of the
      Western Carpathians in Romania, metal mining activities have a long-standing
      tradition. These mining industries created a clearly beneficial economic
      development in the region. But their activities also caused impairments to the
      environment, such as acid mine drainage (AMD) resulting in long-lasting heavy
      metal pollution of waters and sediments. The study, established in the context of
      the ESTROM programme, investigated the impact of metal mining activities both
      from environmental and socioeconomic perspectives and tried to incorporate the
      results of the two approaches into an integrated proposition for mitigation of
      mining-related issues. STUDY SITE: The small Certej catchment, situated in the
      Southern Apuseni Mountains, covers an area of 78 km(2). About 4,500 inhabitants
      are living in the basin, in which metal mining was the main economic sector. An
      open pit and several abandoned underground mines are producing heavy metal-loaded
      acidic water that is discharged untreated into the main river. The solid wastes
      of mineral processing plants were deposited in several dumps and tailings
      impoundment embodying the acidic water-producing mineral pyrite. METHODS: The
      natural science team collected samples from surface waters, drinking water from
      dug wells and from groundwater. Filtered and total heavy metals, both after
      enrichment, and major cations were analysed by inductively coupled plasma optical
      emission spectroscopy (ICP-OES). Major anions in waters, measured by ion
      chromatography, alkalinity and acidity were determined by titration. Solid
      samples were taken from river sediments and from the largest tailings dam. The
      latter were characterised by X-ray fluorescence and X-ray diffraction. Heavy
      metals in sediments were analysed after digestion. Simultaneously, the
      socioeconomic team performed a household survey to evaluate the perception of
      people related to the river and drinking water pollution by way of a logistic
      regression analysis. RESULTS AND DISCUSSION: The inputs of acid mine waters
      drastically increased filtered heavy metal concentrations in the Certej River,
      e.g. Zn up to 130 mg L(-1), Fe 100 mg L(-1), Cu 2.9 mg L(-1), Cd 1.4 mg L(-1) as
      well as those of SO(4) up to 2.2 g L(-1). In addition, river water became acidic
      with pH values of pH 3. Concentrations of pollutant decreased slightly downstream
      due to dilution by waters from tributaries. Metal concentrations measured at
      headwater stations reflect background values. They fell in the range of the
      environmental quality standards proposed in the EU Water Framework Directive for
      dissolved heavy metals. The outflow of the large tailing impoundment and the
      groundwater downstream from two tailings dams exhibited the first sign of AMD,
      but they still had alkalinity. Most dug wells analysed delivered a drinking water
      that exhibited no sign of AMD pollution, although these wells were a distance of
      7 to 25 m from the contaminated river. It seems that the Certej River does not
      infiltrate significantly into the groundwater. Pyrite was identified as the main
      sulphide mineral in the tailings dam that produces acidity and with calcite
      representing the AMD-neutralising mineral. The acid-base accounting proved that
      the potential acid-neutralising capacity in the solid phases would not be
      sufficient to prevent the production of acidic water in the future. Therefore,
      the open pits and mine waste deposits have to be seen as the sources for AMD at
      the present time, with a high long-term potential to produce even more AMD in the
      future. The socioeconomic study showed that mining provided the major source of
      income. Over 45% of the households were partly or completely reliant on financial
      compensations as a result of mine closure. Unemployment was considered by the
      majority of the interviewed persons as the main cause of social problems in the
      area. The estimation of the explanatory factors by the logistic regression
      analysis revealed that education, household income, pollution conditions during
      the last years and familiarity with environmental problems were the main
      predictors influencing peoples' opinion concerning whether the main river is
      strongly polluted. This model enabled one to predict correctly 77% of the
      observations reported. For the drinking water quality model, three predictors
      were relevant and they explained 66% of the observations. CONCLUSIONS: Coupling
      the findings from the natural science and socioeconomic approaches, we may
      conclude that the impact of mining on the Certej River water is high, while
      drinking water in wells is not significantly affected. The perceptions of the
      respondents to pollution were to a large extent consistent with the measured
      results. RECOMMENDATIONS AND PERSPECTIVES: The results of the study can be used
      by various stakeholders, mainly the mining company and local municipalities, in
      order to integrate them in their post-mining measures, thereby making them aware
      of the potential long-term impact of mining on the environment and on human
      health as well as on the local economy.

PMID- 19159961
TI  - [Organ- and function-preserving pancreatic surgery].

PMID- 19159962
TI  - [Lateral anastomosis techniques: Partington-Rochelle and V-shaped excision].
AB  - Characteristic symptoms of chronic pancreatitis are difficult to manage
      conservatively. They include severe pain and endocrine and exocrine
      insufficiency. Surgical treatment with simple and extended draining procedures
      addresses pain relief and the management of chronic pancreatitis-associated
      complications of adjacent organs. Following the assumption that pancreatic duct
      changes with intraductal hypertension are the reason for pain, simple drainage
      procedures have reduced pain in up to 80% of patients, with low morbidity and
      mortality. In case of complications involving adjacent organs with inflammatory
      pancreatic head tumor and stenosis of the distal bile duct, extended drainage
      procedures with limited pancreatic head resection according to Frey and V-shaped
      excision of the ventral aspect of the pancreas have been performed successfully.

PMID- 19159965
TI  - Minisatellite MS32 alleles show population specificity among Thai, Chinese, and
      Japanese.
AB  - Lineages of structurally related alleles at minisatellite MS32 in human
      populations show considerable differentiation at the continental level. However,
      the regional specificity of these lineages remains unknown. We now describe the
      comparison of allele structures in Thai, Han Chinese, and Japanese populations
      with lineages previously established for North Europeans and Africans. The great
      majority of alignable Asian alleles showed their closest structural relative in
      Asia, with few instances of preferential alignment of Asian with European alleles
      and only one isolated incident showing a best match with an African allele.
      Further, there was a strong tendency, most marked for Japanese, for Asian alleles
      to align preferentially with other alleles from the same population, indicating
      strong regional specificity of allele lineages. This rapidly evolving
      minisatellite can therefore serve as a lineage marker for exploring recent events
      in human population history and dissecting population structure at the fine-scale
      level, as well as being an extremely informative DNA marker for personal
      identification.

PMID- 19159963
TI  - [Congenital retinocephalic facial vascular malformation syndrome. Bonnet-Dechaume
      Blanc syndrome or Wyburn-Mason syndrome].
AB  - The congenital retinocephalic facial vascular malformation syndrome is
      characterized by unilateral, nonhereditary retinal and cerebral arteriovenous
      malformations (AVMs) and is occasionally associated with orbital vascular
      changes. Typical signs are facial and oral mucosal vascular changes, rarely with
      changes of the maxilla or mandible. An AVM causes high blood flow because of
      direct connection (shunting) of major vessels without interposition of
      capillaries. Ocular complications include retinal and vitreous hemorrhages,
      edema, venous occlusion (risk of rubeosis iridis and secondary glaucoma).
      Neuroophthalmological changes comprise optic atrophy, papilledema, proptosis,
      pupillary changes, hemianopia, gaze paresis, nystagmus, cranial nerve palsies,
      strabismus, and amblyopia. Neurological complications include headache,
      subarachnoid hemorrhage, convulsions, cerebral hemorrhages, increased
      intracranial pressure, hydrocephalus, and stroke with hemiparesis. Threatening
      oral hemorrhages or epistaxis may rarely occur.

PMID- 19159966
TI  - Positive selection in tick saliva proteins of the Salp15 family.
AB  - When taking their blood meal on the mammalian host, ticks transfer a multitude of
      different proteins from their saliva into the host. Some of these proteins are
      hijacked by pathogens for their own purposes. Borrelia burgdorferi, the Lyme
      disease agent, is critically dependent on the presence of the tick protein Salp15
      when infecting the host. Similarly, Anaplasma phagocytophilum, which causes
      anaplasmosis, needs Salp16, a homologue of Salp15, to get transferred from the
      host into the tick. Here we analyzed whether adaptive evolution has shaped the
      Salp15 protein family. Using site-specific estimates of K(A)/K(S) ratios, we
      identified different positions within the Salp15 protein family which have
      undergone a phase of positive selection. Additionally, we analyzed the B.
      burgdorferi protein interacting with Salp15, OspC. Again, sites showing signs of
      positive selection were identified, although they are more likely a result of the
      antigenic features of OspC than of the influence of Salp15. The identification of
      probably functionally relevant sites in the Salp15 family might direct the
      detailed experimental analysis of their interaction with human and bacterial
      proteins.

PMID- 19159967
TI  - Influence of mowing Artemisia tridentata ssp. wyomingensis on winter habitat for
      wildlife.
AB  - Mowing is commonly implemented to Artemisia tridentata ssp. wyomingensis (Beetle
      & A. Young) S.L. Welsh (Wyoming big sagebrush) plant communities to improve
      wildlife habitat, increase forage production for livestock, and create fuel
      breaks for fire suppression. However, information detailing the influence of
      mowing on winter habitat for wildlife is lacking. This information is crucial
      because many wildlife species depended on A. tridentata spp. wyomingensis plant
      communities for winter habitat and consume significant quantities of Artemisia
      during this time. Furthermore, information is generally limited describing the
      recovery of A. tridentata spp. wyomingensis to mowing and the impacts of mowing
      on stand structure. Stand characteristics and Artemisia leaf tissue crude protein
      (CP), acid detergent fiber (ADF), and neutral detergent fiber (NDF)
      concentrations were measured in midwinter on 0-, 2-, 4-, and 6-year-old fall
      applied mechanical (mowed at 20 cm height) treatments and compared to adjacent
      untreated (control) areas. Mowing compared to the control decreased Artemisia
      cover, density, canopy volume, canopy elliptical area, and height (P < 0.05), but
      all characteristics were recovering (P < 0.05). Mowing A. tridentata spp.
      wyomingensis plant communities slightly increases the nutritional quality of
      Artemisia leaves (P < 0.05), but it simultaneously results in up to 20 years of
      decrease in Artemisia structural characteristics. Because of the large reduction
      in A. tridentata spp. wyomingensis for potentially 20 years following mowing,
      mowing should not be applied in Artemisia facultative and obligate wildlife
      winter habitat. Considering the decline in A. tridentata spp. wyomingensis
      dominated landscapes, we caution against mowing these communities.

PMID- 19159969
TI  - Pragmatics of policy: the compliance of dutch environmental policy instruments to
      European union standards.
AB  - Despite a general decrease in Dutch environmental emission trends, it remains
      difficult to comply with European Union (EU) environmental policy targets.
      Furthermore, environmental issues have become increasingly complex and entangled
      with society. Therefore, Dutch environmental policy follows a pragmatic line by
      adopting a flexible approach for compliance, rather than aiming at further
      reduction at the source of emission. This may be politically useful in order to
      adequately reach EU targets, but restoration of environmental conditions may be
      delayed. However, due to the complexity of today's environmental issues, the
      restoration of environmental conditions might not be the only standard for a
      proper policy approach. Consequently this raises the question how the Dutch
      pragmatic approach to compliance qualifies in a broader policy assessment. In
      order to answer this question, we adapt a policy assessment framework, developed
      by Hemerijck and Hazeu (Bestuurskunde 13(2), 2004), based on the dimensions of
      legitimacy and policy logic. We apply this framework for three environmental
      policy assessments: flexible instruments in climate policy, fine-tuning of
      national and local measures to meet air quality standards, and derogation for the
      Nitrate Directive. We conclude with general assessment notes on the appliance of
      flexible instruments in environmental policy, showing that a broad and
      comprehensive perspective can help to understand the arguments to put such policy
      instruments into place and to identify trade-offs between assessment criteria.

PMID- 19159968
TI  - Historical analysis of SO2 pollution control policies in China.
AB  - Coal is not only an important energy source in China but also a major source of
      air pollution. Because of this, China's national sulfur dioxide (SO(2)) emissions
      have been the highest in the world for many years, and since the 1990s, the
      territory of China's south and southwest has become the third largest acid-rain
      prone region in the world. In order to control SO(2) emissions, the Chinese
      government has formulated and promulgated a series of policies and regulations,
      but it faces great difficulties in putting them into practice. In this
      retrospective look at the history of SO(2) control in China, we found that
      Chinese SO(2) control policies have become increasingly strict and rigid. We also
      found that the environmental policies and regulations are more effective when
      central officials consistently give environmental protection top priority.
      Achieving China's environmental goals, however, has been made difficult by
      China's economic growth. Part of this is due to the practice of environmental
      protection appearing in the form of an ideological "campaign" or "storm" that
      lacks effective economic measures. More recently, better enforcement of
      environmental laws and regulations has been achieved by adding environmental
      quality to the performance assessment metrics for leaders at all levels. To
      continue making advances, China needs to reinforce the economic and environmental
      assessments for pollution control projects and work harder to integrate economic
      measures into environmental protection. Nonetheless, China has a long way to go
      before economic growth and environmental protection are balanced.

PMID- 19159970
TI  - Evaluation of trauma care resources in health centers and referral hospitals in
      Cambodia.
AB  - BACKGROUND: The aim of this study was to evaluate the available resources for
      trauma care at health centers (HCs) and referral hospitals (RHs) in rural
      Cambodia and to examine whether the resources at HCs are allocated on the basis
      of actual need based on the referral distance and number of severely injured
      patients referred to RHs. METHODS: We conducted a cross-sectional facility survey
      by phone interview or mail using structured questionnaires at nationally
      representative samples of 85 HCs and 17 RHs from December 2006 to April 2007. The
      questionnaire included a modified checklist of the guidelines for essential
      trauma care as well as questions on distance for referral and the number of
      injured patients received and referred during the last 3 months. We analyzed the
      association between resource availability at HCs and their need using
      multivariate linear regression. RESULTS: Median (interquartile range) numbers of
      available resources at HCs and RHs were 25.5 (22.0-27.5) and 35 (28-41) among 37
      and 62 essential items, respectively. Basic equipment, including both consumable
      supplies and durable devices and life-saving knowledge/skills, were not
      satisfactory at either HCs or RHs. A longer distance to the RH was associated
      with more knowledge/skills but not with equipment supplies; the number of
      referred patients was not associated with equipment or knowledge/skills.
      CONCLUSIONS: Staff training emphasizing life-saving knowledge/skills and better
      organization and planning to supply physical resources are needed. There is a gap
      between resource allocation and need, which should be addressed through clear
      policies to prioritize remote areas and to allocate resources based on reliable
      injury data.

PMID- 19159971
TI  - High-resolution CT and angiographic evaluation of NexStent wall adaptation.
AB  - Carotid stenting is a minimally invasive treatment for extracranial carotid
      artery stenosis. Stent design may affect technical success and complications in a
      certain subgroup of patients. We examined the wall adaptability of a new closed
      cell carotid stent (NexStent), which has a unique rolled sheet design. Forty-one
      patients had 42 carotid arteries treated with angioplasty and stenting for
      internal carotid artery stenosis. The mean patient age was 65 +/- 10 years. All
      patients underwent high-resolution computed tomographic angiography after the
      stent implantation. Data analysis included pre- and postprocedural stenosis,
      procedure complications, plaque calcification, and stent apposition. We reviewed
      the angiographic and computed tomographic images for plaque coverage and stent
      expansion. All procedures were technically successful. Mean stenosis was reduced
      from 84 +/- 8% before the procedure to 15.7 +/- 7% after stenting. Two patients
      experienced transient ischemic attack; one patient had bradycardia and
      hypotension. Stent induced kinking was observed in one case. Good plaque coverage
      and proper overlapping of the rolled sheet was achieved in all cases. There was
      weak correlation between the residual stenosis and the amount of calcification.
      The stent provides adequate expansion and adaptation to the tapering anatomy of
      the bifurcation.

PMID- 19159972
TI  - Hemosuccus pancreaticus in a patient with iodine allergy: successful diagnosis
      with magnetic resonance imaging and treatment with transarterial embolization
      using carbon dioxide as the contrast medium.
AB  - Hemosuccus pancreaticus (HP) is defined as gastrointestinal bleeding via the
      pancreatic duct and duodenal papilla. Since the bleeding is usually intermittent,
      it often remains undetected by endoscopy. Most cases are diagnosed by contrast
      enhanced computed tomography (CT) or angiography, and the first-line treatment is
      transarterial embolization (TAE). However, in general, these modalities require a
      large amount of iodinated contrast medium. Here, we report the case of a 50-year
      old female with HP due to chronic pancreatitis. Contrast-enhanced CT and ordinary
      angiography were contraindicated for her, as she was allergic to iodine. She was
      diagnosed with HP following gadolinium-enhanced magnetic resonance imaging and
      successfully treated by TAE of the splenic artery with metallic coils using
      carbon dioxide as the contrast medium.

PMID- 19159973
TI  - Genetic transformation of midgut bacteria from the red imported fire ant
      (Solenopsis invicta).
AB  - In our previous study we isolated 10 bacterial species from fourth-instar larval
      midguts of the red imported fire ant, Solenopsis invicta. Here we report the
      genetic transformation and reintroduction of three species (Kluyvera
      cryocrescens, Serratia marcescens, and isolate 38) into the fire ant host. All
      three species were transformed with the plasmid vector, pZeoDsRed. High
      expression levels of DsRed were observed and the plasmid is maintained in these
      bacteria at 37 degrees C in the absence of antibiotic selection for at least 9
      days of subculturing. The transformed bacteria were successfully reintroduced
      into fire ant larvae and survived in the fire ant gut for at least 7 days. Upon
      pupal emergence, 7 days after reintroduction, transformed bacteria can still be
      isolated, however, most were passed out in the meconium. We further demonstrated
      that the engineered bacteria could be spread within the colony by feeding this
      meconium to naive larvae with the aid of worker fire ants.

PMID- 19159974
TI  - Identification of cellulase genes from the metagenomes of compost soils and
      functional characterization of one novel endoglucanase.
AB  - Metagenomics, a new research field developed over the past decade, aims to
      identify potential enzymes from nonculturable microbes. In this study, genes
      encoding three glycoside hydrolase family (GHF) 9 endoglucanases and one GHF 5
      endoglucanase were cloned and identified from the metagenome of the compost
      soils. The shared identities between the predicted amino acid sequences of these
      genes and their closest homologues in the database were less than 70%. One GHF 9
      endoglucanase, Umcel9B, was further characterized. The recombinant protein,
      Umcel9B, showed activity against carboxymethyl cellulose, indicating that Umcel9B
      is an endoactive enzyme. Enzymatic activity occurs optimally at a pH of 7.0 and a
      temperature of 25 degrees C.

PMID- 19159975
TI  - An efficient RNA extraction method for estimating gut microbial diversity by
      polymerase chain reaction.
AB  - An extraction method was developed to recover high-quality RNA from rumen digesta
      and mouse feces for phylogenetic analysis of metabolically active members of the
      gut microbial community. Four extraction methods were tested on different amounts
      of the same samples and compared for efficiency of recovery and purity of RNA.
      Trizol extraction after bead beating produced a higher quantity and quality of
      RNA than a similar method using phenol/chloroform. Dissociation solution produced
      a 1.5- to 2-fold increase in RNA recovery compared with phosphate-buffered saline
      during the dissociation of microorganisms from rumen digesta or fecal particles.
      The identity of metabolically active bacteria in the samples was analyzed by
      sequencing 87 amplicons produced using bacteria-specific 16S rDNA primers, with
      cDNA synthesized from the extracted RNA as the template. Amplicons representing
      the major phyla encountered in the rumen (Firmicutes, 43.7%; Proteobacteria,
      28.7%; Bacteroidetes, 25.3%; Spirochea, 1.1%, and Synergistes, 1.1%) were
      recovered, showing that development of the RNA extraction method enables RNA
      based analysis of metabolically active bacterial groups from the rumen and other
      environments. Interestingly, in rumen samples, about 30% of the sequenced random
      16S rRNA amplicons were related to the Proteobacteria, providing the first
      evidence that this group may have greater importance in rumen metabolism than
      previously attributed by DNA-based analysis.

PMID- 19159976
TI  - Exploration of Csp genes from temperate and glacier soils of the Indian Himalayas
      and in silico analysis of encoding proteins.
AB  - The metagenomic Csp library was constructed from the temperate and glacier soils
      of central Himalaya, India followed by polymerase chain reaction (PCR)
      amplification. The library was further screened for low-temperature adaptation,
      and the positive recombinants were sorted out by determining changes in the
      melting temperature (Tm). A homology search of cloned sequence showed their
      identity with the Csp genes of Pseudomonas fluorescens, Psychrobacter
      cryohalolentis K5, and Shewanella spp MR-4. Amino acid sequence analysis
      annotated the presence of conserved aromatic and basic amino acids as well as RNA
      binding motifs from the cold shock domain. Furthermore, a PROSITE scan showed a
      moderate identity of less than 60% with the known cold shock-inducible proteins
      (ribosomal proteins, rbfA, DEAD-box helicases), cold acclimation protein, and
      temperature-induced protein (SRP1/TIP1). This study highlighted the prevalence of
      Csp genes from cold Himalayan environments that can be explored for tailor-made
      crop constructions in future.

PMID- 19159977
TI  - Laparoscopy or fast-track surgery, or both?

PMID- 19159978
TI  - Recruitment of neurons and loudness. Commentary on "Encoding intensity in ventral
      cochlear nucleus following acoustic trauma: implications for loudness
      recruitment" by Cai et al. J. Assoc. Res. Otolaryngol. DOI: 10.1007/s10162-008
      0142-y.

PMID- 19159979
TI  - Chemical composition of the defensive secretion of the longhorned beetle,
      Chloridolum loochooanum.
AB  - Adults of the longhorned beetle, Chloridolum loochooanum Gressitt (Coleoptera:
      Cerambycidae) emit a white frothy secretion from their metasternal glands. This
      defensive substance contains cyclopentanoid monoterpenoids (iridodials), whose
      structures were elucidated by gas chromatography-mass spectrometry (GC-MS) and
      nuclear magnetic resonance (NMR) analyses that compared the naturally occurring
      structures with synthesized versions. Optically active citronellals, [(S)-, (R)-,
      and (S)/(R)- mixture], were used as starting materials for synthesizing the
      corresponding iridodials for the determination of the absolute configuration of
      the natural product. The retention time of (2S)-iridodial, derived from (S)
      citronellal, corresponded to that of C. loochooanum iridodial by enantioselective
      GC analysis. Thus, we suggest that the absolute configuration of C. loochooanum
      iridodial is (1R,2S,5S)-iridodial.

PMID- 19159980
TI  - Constitutive and induced activities of defense-related enzymes in aphid-resistant
      and aphid-susceptible cultivars of wheat.
AB  - Phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POD)
      are considered important biochemical markers in host plant resistance against
      pest insects. Constitutive activity of these enzymes was analyzed in resistant
      and susceptible wheat cultivars against cereal aphid Sitobion avenae (F.) at
      various developmental stages, i.e., tillering, stem elongation, flag leaf, and
      ear. Following aphid infestation, the activity of these enzymes was determined at
      the flag leaf and ear stages. Resistant cultivars exhibited greater constitutive
      PAL activity than susceptible ones at the tillering, stem elongation, and flag
      leaf stages. Aphid infestation enhanced levels of PAL activity in the flag leaf
      and ear stages in both resistant and susceptible cultivars. Constitutive PPO
      activity was higher in the resistant cultivars at all developmental stages. Aphid
      infestation induced increases in PPO activity in the flag leaf and ear stages of
      one susceptible cultivar, whereas induction in resistant cultivars was weaker.
      Resistant cultivars showed greater constitutive POD activity in the tillering,
      stem elongation, and flag leaf stages, while aphid infestation induced POD
      activity in all cultivars, especially in susceptible ones. The potential role of
      PAL, PPO, and POD in wheat defense against aphid infestation is discussed.

PMID- 19159981
TI  - Herbivore-induced volatiles in the perennial shrub, Vaccinium corymbosum, and
      their role in inter-branch signaling.
AB  - Herbivore feeding activates plant defenses at the site of damage as well as
      systemically. Systemic defenses can be induced internally by signals transported
      via phloem or xylem, or externally transmitted by volatiles emitted from the
      damaged tissues. We investigated the role of herbivore-induced plant volatiles
      (HIPVs) in activating a defense response between branches in blueberry plants.
      Blueberries are perennial shrubs that grow by initiating adventitious shoots from
      a basal crown, which produce new lateral branches. This type of growth constrains
      vascular connections between shoots and branches within plants. While we found
      that leaves within a branch were highly connected, vascular connectivity was
      limited between branches within shoots and absent between branches from different
      shoots. Larval feeding by gypsy moth, exogenous methyl jasmonate, and mechanical
      damage differentially induced volatile emissions in blueberry plants, and there
      was a positive correlation between amount of insect damage and volatile emission
      rates. Herbivore damage did not affect systemic defense induction when we
      isolated systemic branches from external exposure to HIPVs. Thus, internal
      signals were not capable of triggering systemic defenses among branches. However,
      exposure of branches to HIPVs from an adjacent branch decreased larval
      consumption by 70% compared to those exposed to volatiles from undamaged
      branches. This reduction in leaf consumption did not result in decreased volatile
      emissions, indicating that leaves became more responsive to herbivory (or
      "primed") after being exposed to HIPVs. Chemical profiles of leaves damaged by
      gypsy moth caterpillars, exposed to HIPVs, or non-damaged controls revealed that
      HIPV-exposed leaves had greater chemical similarities to damaged leaves than to
      control leaves. Insect-damaged leaves and young HIPV-exposed leaves had higher
      amounts of endogenous cis-jasmonic acid compared to undamaged and non-exposed
      leaves, respectively. Our results show that exposure to HIPVs triggered systemic
      induction of direct defenses against gypsy moth and primed volatile emissions,
      which can be an indirect defense. Blueberry plants appear to rely on HIPVs as
      external signals for inter-branch communication.

PMID- 19159982
TI  - BRAF mutation in papillary thyroid microcarcinoma: the promise of better risk
      management.

PMID- 19159983
TI  - Liver resection improves the survival of patients with multiple hepatocellular
      carcinomas.
AB  - BACKGROUND: According to current guidelines of hepatocellular carcinoma (HCC)
      treatment, multiple HCCs are usually not suitable for surgical resection.
      However, surgical resection is still possible for patients with multiple HCCs.
      The role of hepatic resection vs transarterial chemoembolization (TACE) for
      multiple HCCs should be further clarified. METHODS: We retrospectively enrolled
      1065 patients with multiple HCCs. Among them, 294 received surgical resection,
      367 received transarterial chemoembolization (TACE), and 404 received
      chemotherapy or supportive care. Three staging systems (TNM, CLIP, and BCLC) were
      used for comparison of stage-specific survival between different treatment
      modalities. RESULTS: The median survival of multiple HCC patients who received
      surgical resection was 37.9 months, while it was 17.3 months in TACE group, and
      2.8 months in supportive group (P < .001). The 1-year, 3-year, 5-year survival
      rates for surgical group were 77.4%, 51.9%, and 36.6%, respectively. Kaplan-Meier
      survival analysis demonstrated that patients who received surgical resections had
      the best survival, followed by TACE and supportive care. For patients of the same
      stage, surgical resection yields better results than TACE. Surgery could offer
      better survival than TACE for patients either within or beyond Milan's criteria.
      CONCLUSIONS: Our results indicate that if patients have preserved liver
      functions, hepatic resection is helpful, even for patients with multiple HCCs.

PMID- 19159984
TI  - T2 mapping of articular cartilage of glenohumeral joint with routine MRI
      correlation--initial experience.
AB  - The evaluation of articular cartilage currently relies primarily on the
      identification of morphological alterations of the articular cartilage. Unlike
      anatomic imaging, T2 mapping is sensitive to changes in the chemical composition
      and structure of the cartilage. Clinical evaluation of T2 mapping of the
      glenohumeral joint has not been previously reported. The objectives of this study
      were to evaluate the feasibility of magnetic resonance T2 mapping of the
      glenohumeral joint in routine clinical imaging, to assess the normal T2 mapping
      appearance of the glenohumeral joint, and to compare the findings on T2 maps to
      conventional MR pulse sequences. Magnetic resonance imaging (MRI) examinations of
      27 shoulders were performed in a routine clinical setting. All studies included
      acquisition of T2 mapping using a dedicated software. The T2 maps were analyzed
      along with the routine MR exam and correlation of cartilage appearance on T2 map
      and on conventional MR sequences. T2 imaging maps were obtained successfully in
      all patients. T2 maps and routine MRI correlated in cases of normal cartilage and
      prolonged T2 values and cartilage defects. In four cases, increased T2 relaxation
      times in the cartilage and cartilage defects were more apparent on T2 maps.
      Acquisition of T2 maps at the time of routine MRI scanning is feasible and not
      time-consuming.

PMID- 19159985
TI  - Hybrid modeling of noise reduction by a negatively autoregulated system.
AB  - We analyze the reduction of intrinsic noise caused by transition of a promoter
      between its active and inactive state in a negatively regulated genetic network,
      i.e., transcription of the gene is inhibited by its own gene product. To measure
      the noise attenuation, we compare its behavior to an inducible gene for which
      activation and deactivation of the gene take place at constant rates. As a model,
      we choose a hybrid approach in which some of the reaction channels are modeled as
      discrete events, and other reactions are modeled as continuous processes. Such a
      model is appropriate for investigations of noise caused by low reactant numbers.
      By focusing on intrinsic noise originating from the switching behavior of the
      regulatory system of a particular gene, we model only the transition between two
      different promoter states as a discrete event. We show that the stationary
      distributions of the unregulated and the autoregulated system are given as a
      solution of two coupled ordinary differential equations. Also, beside the
      distribution densities, the first two central moments are derived in closed
      analytical forms. We give conditions on the parameters when one or the other
      system shows lower fluctuations.

PMID- 19159986
TI  - Comparison of one-stage managements of obstructing left-sided colon and rectal
      cancer: stent-laparoscopic approach vs. intraoperative colonic lavage.
AB  - PURPOSE: We evaluated the operative outcomes of laparoscopic surgery following
      self-expandable metallic stent compared to one-stage emergency surgical
      treatment. METHODS: From April 1996 to October 2007, 95 consecutive patients with
      left-sided malignant colorectal obstruction were enrolled. Twenty-five patients
      were assigned to the preoperative stenting and elective laparoscopic surgical
      treatment group (SLAP) and 70 to the emergency open surgery with intraoperative
      colon lavage group (OLAV). RESULTS: Among the 25 patients in the SLAP group, a
      primary anastomosis was possible in all patients and a diverting stoma was needed
      in one patient. The operative time was shorter in the SLAP group (198.53 vs.
      262.17 min, P = 0.002). Tumor size, number of retrieved lymph nodes, and
      pathological stage were similar in both groups. The rate of anastomotic failure
      was similar and postoperative complications occurred less in the SLAP group (5.9%
      vs. 31.4%, P = 0.034). The passage of flatus and oral intake were resumed earlier
      in the SLAP group (2.88 vs. 3.68 days, P = 0.046 and 5.18 vs. 6.65 days, P <
      0.001, respectively). The postoperative hospital stay was shorter in the SLAP
      group (10 vs. 15.4 days, P = 0.013). CONCLUSIONS: In patients with left-sided
      malignant colon and rectal obstruction, laparoscopic surgery after SEMS could be
      safely performed with successful early postoperative outcomes.

PMID- 19159987
TI  - Advances in circular stapling techniques for gastric bypass: the circular stapler
      introducer.
AB  - BACKGROUND: Modern laparoscopic bariatric surgery relies strongly on stapling
      devices and the perfection of the anastomotic technique is at the core of the
      patient's safety. METHODS: Circular stapler anastomosis is a common technique for
      performing gastro-jejunostomy in gastric bypass surgery. In obese patients,
      transabdominal circular stapler introduction can be challenging and associated
      with morbidity. To overcome these technical obstacles, we have developed a new
      device, circular stapler introducer (CSI) to assist both the abdominal wall
      passage of the circular staplers and its introduction into the jejunum. RESULTS:
      The CSI facilitates the insertion of the circular stapler not only into the
      abdomen but also into the jejunum enhancing safety and swiftness of laparoscopic
      Roux-en-Y gastric bypass. CONCLUSIONS: Our innovative CSI device facilitates this
      part of the operation significantly and makes the performance of bariatric
      surgery more convenient.

PMID- 19159989
TI  - Initial clinical experience with a selective A2A receptor agonist, regadenoson,
      in a patient with end-stage renal disease on hemodialysis.

PMID- 19159990
TI  - Prognostic value of myocardial perfusion-gated SPECT in patients with ischemic
      cardiomyopathy.
AB  - BACKGROUND: There are no extensive series in which risk stratification of
      patients with ischemic cardiomyopathy (IC) is based on their rest and exercise
      and scintigraphic characteristics. The purpose of our study was to analyze rest
      and exercise myocardial perfusion-gated SPECT variables for prognosis in patients
      with ischemic IC. METHODS AND RESULTS: Prospective cohort study. A study was
      performed in 167 patients with IC who consecutively underwent rest myocardial
      perfusion-gated SPECT. In addition, stress SPECT was performed on 137 of these
      patients. During an average follow-up of 2.3 +/- 1.2 years, cardiac mortality
      (CM) was 17.4%. Independent predictors of CM in rest-gated SPECT were the
      positive criteria for myocardial viability (P = 0.027; Hazard risk, HR: 5.1; 95%
      CI: 1.2-21.4). In the 137 patients who underwent stress-gated SPECT, predictors
      were scintigraphic criteria for viability plus ischemia (P = 0.026; HR: 3.6; 95%
      CI: 1.16-11.2) and exercise duration < or = 5 minutes (P = 0.04; HR: 2.7; 95% CI:
      1.01-7.36). Coronary angiography variables, performed in 111 patients, did not
      significantly modify the prognostic value of non-invasive testing. CONCLUSION:
      Myocardial perfusion-gated SPECT improves prognostic stratification of patients
      with IC.

PMID- 19159991
TI  - Highlights of the 2008 scientific sessions of the American Society of Nuclear
      Cardiology : Boston, Massachusetts, 10-14 September 2008.

PMID- 19159992
TI  - Of fight and flight.

PMID- 19159993
TI  - Resting muscle sympathetic nerve activity, cardiac metaiodobenzylguanidine
      uptake, and exercise tolerance in patients with left ventricular dysfunction.
AB  - BACKGROUND: Sympathetic nerve overactivity and reduced exercise tolerance are
      characteristic features of patients with heart failure. However, to what extent
      sympathetic nerve overactivity contributes to limiting exercise tolerance has not
      been clearly defined. METHODS: Myocardial iodine 123-metaiodobenzylguanidine
      (MIBG) scintigraphy, muscle sympathetic nerve activity (MSNA), and
      cardiopulmonary exercise testing were performed within 3 days in 30 patients with
      left ventricular dysfunction (LVD). Cardiac sympathetic nerve activity was
      estimated using H/M ratio and washout rate (WR) of 123I-MIBG imaging. MSNA was
      recorded by microneurography. RESULTS: The patients with peak VO(2) < 20
      mL/minute/kg (group II, n = 15) had significantly higher MSNA and WR, and lower
      H/M ratio than those with peak VO(2) > or = 20 mL/minute/kg (group I, n = 15) (P
      < .05). Peak VO(2) had negative correlations with MSNA and WR (r = 0.58, 0.56),
      and positive correlations with early H/M ratio and delayed H/M ratio (r = 0.71,
      0.75) in group II. Moreover, MSNA had negative correlations with early H/M ratio
      and delayed H/M ratio (r = 0.78, 0.66), and a positive correlation with WR (r =
      0.79) in group II. However, similar relations were not found in group I.
      CONCLUSIONS: A link between cardiac and peripheral sympathetic nerve activities
      contributed to limiting exercise tolerance in patients with LVD patients and
      reduced exercise tolerance.

PMID- 19159994
TI  - Dual "motion-frozen heart" combining respiration and contraction compensation in
      clinical myocardial perfusion SPECT imaging.
AB  - OBJECTIVES: This article assesses the effect of a new correction technique
      ("motion-frozen heart") which compensates for the previously described nonuniform
      blurring of myocardial perfusion imaging (MPI) due to respiration motion or
      cardiac contraction. METHODS: Respiratory and ECG-gated one-day (99m)Tc-MIBI MPI
      studies performed in 48 patients were evaluated. MPI scans were acquired on a
      gamma camera supporting list-mode functionality synchronized with an external
      respiratory strap and an ECG device. Respiratory and cardiac-gated bins were
      generated using the acquired list file. Respiratory-gated bins were corrected for
      respiratory motion, followed by correction for cardiac contraction motion. In
      addition, cardiac contraction correction was applied to cardiac-gated bins
      uncorrected for respiratory motion. Bullseye maps were generated for uncorrected
      MPI studies, as well as following correction for respiratory motion, cardiac
      contraction, and both. The mean difference between each of the correction vs the
      uncorrected bullseye was calculated. Visual assessment of image quality,
      severity, and extent of the uncorrected perfusion images and following each of
      the corrections was performed. RESULTS: Average motion due respiration was 7.0 +/
      2.6 mm in the axial plane. The maximal score difference in segmental uptake
      greater than 10% was found in 2%, 15%, and 25% following respiratory correction,
      contraction correction, and dual corrections, respectively. Percent of scans
      classified with an excellent image quality was 13%, 21%, 42%, and 52% for the
      uncorrected images and following respiratory correction, contraction correction,
      and dual corrections, respectively. CONCLUSIONS: A technique that compensates for
      motion of the heart due to respiration and cardiac contraction in MPI-SPECT was
      evaluated. Compensating for both respiration and cardiac contraction had the
      greatest effect on perfusion images resulting in significantly improved image
      quality.

PMID- 19159995
TI  - Clinical utility of estimated glomerular filtration rate in patients undergoing
      gated SPECT.
AB  - BACKGROUND: Chronic kidney disease is a major risk factor for coronary artery
      disease (CAD). The aim of the study was to examine the association between
      estimated glomerular filtration rate (GFR), presence of CAD, and prognosis in
      patients with reversible perfusion defects at gated single-photon emission
      computed tomography (g-SPECT). METHODS: Six hundred fifty-eight subjects who had
      undergone stress/rest g-SPECT for evaluation of myocardial ischemia were divided
      into two groups according to the presence of CAD, defined by a 70% diameter
      stenosis in at least one major vessel or principal side branch at coronary
      angiography. RESULTS: GFR was lower in patients with CAD and after adjusting for
      several clinical characteristics through multivariate logistic regression
      analysis, reduced (<60 mL/min/1.73 m(2)) GFR remained a significant predictor of
      CAD (HR 1.80, 95% CI 1.04 to 3.12, P = .036). In addition, reduced GFR was
      associated with a greater extent of myocardial ischemia, assessed through the
      summed difference score, as well as with an increase in both total and cardiac
      mortality. CONCLUSIONS: In patients with a positive g-SPECT scan, GFR is an
      accurate marker of CAD and is directly correlated to the extent of myocardial
      ischemia. Furthermore, reduced GFR had an adverse impact on survival in this
      particular population.

PMID- 19159996
TI  - Effects of exercise on the duration of diastole and on interventricular phase
      differences in patients with hypertrophic cardiomyopathy: relationship to cardiac
      output reserve.
AB  - BACKGROUND: Our study sought to characterize the effect of exercise on the
      duration of left ventricular (LV) diastole and interventricular dyssynchrony in
      patients with hypertrophic cardiomyopathy (HCM). We hypothesized that an
      abnormally shortened diastolic time may adversely affect cardiac performance.
      METHODS: We studied 49 symptomatic patients with HCM during incremental exercise.
      Twenty-nine patients had obstructive disease (HOCM) and 20 no resting or
      provocable gradient (HNCM). Right heart catheterization and high temporal
      resolution radionuclide angiography were simultaneously performed. The loss of
      diastolic time per beat (LDT(RR)) was quantified using a regression equation
      obtained from a healthy control group (n = 30). RESULTS: During rest and peak
      exercise, a significant shortening of the relative duration of LV diastole (35.6
      +/- 5 vs. 38.0 +/- 3 s/min and 29.3 +/- 6 vs. 32.4 +/- 3 s/min; P < or = .02) and
      an increased interventricular phase delay were evident in patients with HOCM
      compared to controls. Baseline and peak exercise LDT(RR) values were inversely
      related to cardiac output reserve and exercise duration. In multivariate
      analysis, LDT(RR) at peak exercise was identified as an independent predictor of
      cardiac output reserve. CONCLUSIONS: In HOCM, baseline abnormalities of the
      relative duration of LV systolic and diastolic time aggravate during exercise.
      The disproportionate shortening of diastolic time may significantly impair
      cardiac efficiency by restricting diastolic filling.

PMID- 19159997
TI  - International variations in the ischemic burden post-acute myocardial infarction:
      prognostic implications.
AB  - OBJECTIVES: To determine if there is a variation in the ischemic burden post
      acute myocardial infarction (AMI), as assessed by myocardial perfusion imaging
      (MPI), between different populations in different geographic locations and to see
      if this variation is associated with different clinical outcomes. METHODS AND
      RESULTS: We characterized the MPI findings in 104 stable patients who were
      hospitalized with AMI at the American University of Beirut Medical Center
      (AUBMC), a tertiary referral hospital in an East Mediterranean country and we
      compared them to 126 patients who were enrolled according to a similar protocol
      in a previous study done at Baylor College of Medicine (BCM), Houston, Texas.
      There were no differences between the two populations with respect to prevalence
      of diabetes, hypertension, smoking, the use of thrombolysis, percentage of
      anterior MIs, Q-wave MIs, and multivessel disease on coronary angiography.
      However, the quantified ischemic defect size in the BCM population was double
      that in the AUBMC population (12 +/- 12% vs 6 +/- 8%, P < .01). This was
      associated with almost doubling of the 1 year event rate of death/myocardial
      infarction (18.3% vs 10.6%, P = .02) in the BCM population. CONCLUSION: Our study
      suggests that the ischemic burden post-AMI, as assessed by MPI, might vary
      between different populations in different geographic locations. This variation
      carries important prognostic implications and is associated with different
      patient outcomes.

PMID- 19159998
TI  - Perfusion and wall motion abnormalities in a patient with diabetic ketoacidosis.

PMID- 19159999
TI  - To compare the efficacy and safety of nifedipine sustained release with Ginkgo
      biloba extract to treat patients with primary Raynaud's phenomenon in South
      Korea; Korean Raynaud study (KOARA study).
AB  - This study examined the efficacy and safety of nifedipine sustained release
      (nifedipine SR) compared with Ginkgo biloba extract as treatment for primary
      Raynaud's phenomenon (RP) in Korea. Primary RP were screened and assigned to
      either the nifedipine SR group (Group N) or the Ginkgo biloba extract group
      (Group G) in the ratio of 2:1. After a run-in period of 2 weeks, patients
      received treatment for 8 weeks. We observed the percent improvement of the RP
      attack rate between before and after the 8-week treatment. Ninety-three subjects
      were randomly assigned. The percent improvement in Group N was 50.1% at 8 weeks
      after treatment, while it was 31.0% in Group G (p = 0.03). No serious adverse
      events occurred, and almost adverse events were mild and improved without
      specific treatment. nifedipine SR was more effective than Ginkgo biloba extract
      for treatment of primary RP in Korean patients. Both drugs were tolerable with
      primary RP patients.

PMID- 19160001
TI  - Cardiac carcinoid: tricuspid delayed hyperenhancement on cardiac 64-slice
      multidetector CT and magnetic resonance imaging.
AB  - INTRODUCTION: Carcinoid heart disease is a rare condition in adults. Its
      diagnosis can be easily missed in a patient presenting to a primary care setting.
      We revised the advantages of using coronary multidetector computed tomography
      (MDCT) and cardiac magnetic resonance imaging (MRI) in diagnosing this condition.
      MATERIALS AND METHODS: We studied a 65-year-old patient with carcinoid heart
      disease and right heart failure using transthoracic Doppler-echocardiogram,
      cardiac MDCT and MRI. Cardiac echocardiogram revealed marked thickening and
      retraction of the tricuspid leaflets with dilated right atrium and ventricle.
      Cardiac MDCT and MRI demonstrated fixation and retraction of the tricuspid
      leaflets with delayed contrast hyperenhancement of the tricuspid annulus.
      CONCLUSION: This case demonstrates fascinating imaging findings of cardiac
      carcinoid disease and highlights the increasing utility of contrast-enhanced MRI
      and cardiac MDCT in the diagnosis of this interesting condition.

PMID- 19160000
TI  - Rehabilitation of chronic whiplash: treatment of cervical dysfunctions or chronic
      pain syndrome?
AB  - Chronic whiplash-associated disorders (WAD) remains a challenging condition for
      clinicians. There is substantial evidence for the presence of various cervical
      dysfunctions (e.g., increased cervical muscle tone and impaired cervical movement
      control), but their contribution to the complex clinical picture of subjects with
      chronic WAD seems rather limited. There is consistent evidence for increased
      responsiveness of the central nervous system in those with chronic WAD, and
      central pain processing is likely to play a crucial role in the transition from
      an acute whiplash trauma towards chronic WAD. The manuscript explains how our
      current understanding of chronic WAD can be used to steer the content of
      conservative interventions and how treatment of cervical dysfunctions in patients
      with chronic WAD should account for the processes involved in chronicity. It is
      recommended to prevent sensorimotor incongruence, target cognitive-emotional
      sensitization, and apply a cognitive behavioral therapy-guided exercise program.

PMID- 19160003
TI  - Fibronectin promotes the phorbol 12-myristate 13-acetate-induced macrophage
      differentiation in myeloid leukemia cells.
AB  - The extracellular matrix plays a critical role in macrophage maturation. In this
      study, the HL60 cell line was used as a model of leukemic myeloid cell
      differentiation. We assessed the ability of HL60 cells cultured on fibronectin
      substratum prior to phorbol 12-myristate 13-acetate (PMA) induction to
      differentiate into terminally differentiated macrophages. Beside their
      distinctive macrophage morphology, they expressed antigen receptors CD14, TLR2,
      TLR4 and CD68, and displayed enhanced phagocytic activity and production of
      reactive oxygen species. Expression of CD13, CD33, CD15 and alpha-naphthyl
      acetate esterase was also maintained, however, differentiated HL60 cells were HLA
      DR and CD1a negative. Here, we describe the enhanced capacity of fibronectin
      adherent HL60 cells to differentiate into macrophages in response to PMA.

PMID- 19160004
TI  - Comment on national survey of endoscopic thymectomy: survey report from the
      Japanese Association for Research on the Thymus.

PMID- 19160005
TI  - History and current status of bronchoplastic surgery for lung cancer.
AB  - Sleeve lobectomy for carcinoma of the lung was first described as a compromised
      operation for patients whose pulmonary reserve was considered inadequate to
      permit pneumonectomy. Since then, many authors have suggested that
      bronchoplasties may provide as good if not better results than pneumonectomy in
      selected cases of primary carcinoma of the lung involving the proximal bronchial
      tree. In all reported series, lesions in the hilum of the right upper lobe are
      the commonest indication for sleeve lobectomy, although all lobes and segments of
      the lungs may on occasion be involved with tumors that are amenable to some form
      of lung-sparing bronchoplastic procedure. As a general statement, bronchoplasties
      should be considered in any case of lung cancer that can be completely resected
      by these techniques although some controversy persists about the application of
      these procedures in patients with N(1) or N(2) disease. Published reports
      document a 30-day operative mortality of 0%-5%. Complications peculiar to sleeve
      lobectomy are an increased incidence of retained secretions, bronchovascular
      fistulas, and a potential for an increased incidence of local recurrence. Most
      major reports document a 5-year survival of 40%-50% and functional results that
      are significantly better than those obtained following pneumonectomy.

PMID- 19160007
TI  - National survey of endoscopic thymectomy: survey report from the Japanese
      Association for Research on the Thymus.
AB  - Currently, no specific item regarding endoscopic thymectomy for nonthymomatous
      myasthenia gravis is listed in the standards of deciding medical service fees. To
      understand the present situation regarding the medical fee-for-service for
      endoscopic thymectomy, a questionnaire survey was conducted involving the
      institutions and members participating in the Japanese Association for Research
      on the Thymus. Of 101 responding institutions, 18 (18%) reported basically
      performing endoscopic thymectomy in all qualifying patients, and 32% of the
      institutions reported mainly performing median sternotomy but sometimes
      performing endoscopic thymectomy. The methods of approaching endoscopic
      thymectomy varied among the institutions, but most included endoscopic clips or
      ultrasound-driven scalpels as well as anterior chest wall lifting devices. A
      total of 214 patients underwent thymectomy in 2004 in the responding
      institutions, of whom 77 patients (32%) underwent endoscopic thymectomy. In
      total, 71% of the responding institutions answered that a specific item regarding
      endoscopic thymectomy should be listed in the standards for deciding medical
      service fees.

PMID- 19160006
TI  - Mitral valve repair for degenerative disease with leaflet prolapse: to improve
      long-term outcomes.
AB  - PURPOSE: Residual mitral regurgitation (MR) is a risk factor of reoperation. Here
      we report the midterm results of mitral valve repair for degenerative disease
      with mitral valve prolapse and identify important factors for durable repair.
      METHODS: From April 1999 to September 2007, 116 patients with leaflet prolapse
      (59 men; mean age 63 years) underwent mitral valve repair; they consisted of 19
      anterior, 67 posterior, 23 bileaflet, and 7 isolated commissures. The mean
      clinical and echocardiographic follow-ups were at 4.1 +/- 2.3 and 3.3 +/- 2.4
      years, respectively. RESULTS: Altogether, 12 patients showed recurrent moderate
      or severe MR during the follow-up period; and 10 of the 12 patients (83.8%) had
      recurrent moderate or severe MR within 1.5 years. Causes of early MR recurrence
      were dehiscence of sutured segments and ineffectiveness of the artificial chords.
      The rates of freedom from reoperation at 3 and 7 years were 95.3% +/- 2.0% and
      91.0% +/- 4.7%, respectively. The rates of freedom from recurrent moderate or
      severe MR at 3 and 7 years were 90.5% +/- 2.9% and 83.8% +/- 5.9%, respectively.
      CONCLUSIONS: The prevention of dehiscence of the sutured segment and
      reestablishment of coaptation using artificial chords are imperative to maintain
      the durability of mitral valve repair for patients with degenerative disease.

PMID- 19160008
TI  - Evaluation of chest computed tomography in patients after pneumonectomy to
      predict contralateral pneumothorax.
AB  - PURPOSE: Contralateral pneumothorax is a severe complication after pneumonectomy.
      We evaluated the mediastinal shift and the residual lung in patients who had
      undergone pneumonectomy to predict the incidence of contralateral pneumothorax.
      METHODS: We evaluated 21 cases of pneumonectomy performed from 1996 to 2006. For
      this study, we excluded patients with recurrent neoplasm, empyema, or hemothorax.
      We reviewed the computed tomography (CT) results of 13 patients who had undergone
      pneumonectomy to compare the bullae in the residual lungs, carina shifts, and
      herniation of the residual lungs before and after pneumonectomy. When evaluating
      the degree of herniation 4-6 cm below the carina, the anterior and posterior
      pulmonary hernias were classified as grade A, B, or C. We also investigated the
      preoperative respiratory function in all 13 patients. Results. Two patients
      suffered contralateral pneumothorax after left pneumonectomy. Both patients who
      suffered contralateral pneumothorax after pneumonectomy had bullae. The
      percentage forced expiratory volume in 1 s (FEV(1.0%)) was <70% in these two
      patients. Carina shifts and lung herniation were found to be greater after left
      pneumonectomy than after right pneumonectomy. CONCLUSION: The bullae in the lung
      and obstructive pulmonary disease are associated not only with spontaneous
      pneumothorax but also with contralateral pneumothorax after pneumonectomy. Lung
      herniation and mediastinal shift are greater after left pneumonectomy than after
      right pneumonectomy, which may be related to contralateral pneumothorax after
      pneumonectomy.

PMID- 19160009
TI  - Bilateral subdural hematoma following aortic root and subtotal aortic arch
      replacement.
AB  - We report herein a case of subdural hematoma following aortic root and subtotal
      aortic arch replacement with selective cerebral perfusion in a 78-year-old woman.
      Her level of consciousness gradually deteriorated on postoperative day (POD) 2.
      Subdural hematoma, including fresh bleeding in bilateral frontal and parietal
      regions, was detected on brain computed tomography (CT) on POD 3. No head injury
      had been sustained previously. As the brain was not under pressure and
      disturbance of consciousness improved the next day, she was observed
      conservatively with follow-up brain CT. The subdural hematoma disappeared within
      about 2 months. The patient recovered completely and was discharged without
      sequelae.

PMID- 19160010
TI  - Pulmonary autograft patch aortoplasty for reconstruction of an interrupted aortic
      arch associated with an aortopulmonary window.
AB  - We present here an infant with an aortopulmonary window associated with an
      interrupted aortic arch. Single-stage repair with a pulmonary autograft patch for
      augmentation of the interrupted aortic arch repair was performed. Transpulmonary
      patch closure was used to repair the aortopulmonary window. A computed tomography
      scan at the 1-month follow-up demonstrated a reconstructed aortic arch without
      obstruction, kinking, or any sign of bronchial or branch pulmonary artery
      compression.

PMID- 19160011
TI  - Asymptomatic severe carotid stenosis undergoing staged carotid artery stent and
      coronary artery bypass grafting: decisive role of brain single photon emission
      computed tomography.
AB  - Effort angina of a 70-year-old man was diagnosed as due to triple coronary vessel
      disease, and he was scheduled to undergo coronary artery bypass surgery.
      Preoperative carotid duplex scan revealed more than 75% stenosis of the right
      internal carotid artery, which was functionally proven to be significantly
      ischemic on brain single photon emission computed tomography. Although he was
      neurologically asymptomatic, we chose staged surgery for fear of stroke during
      coronary artery bypass surgery. He had successful carotid artery stenting first
      by neurosurgeons; then, 2 months later he underwent uneventful coronary artery
      bypass surgery. This experience prompted us to report the case.

PMID- 19160012
TI  - Pleomorphic adenoma of the main bronchus in an adult treated using a wedge
      bronchiectomy.
AB  - A 34-year-old woman had complained of dyspnea on exertion for 3 months and was
      found to have a volume loss of the left lung. A smooth, vascularized, whitish
      nodular mass obstructing the orifice of the left main bronchus was noted on
      bronchoscopy. We performed a deep wedge resection of the main bronchus,
      preserving the lung parenchyma. Histopathologically, the tumor specimen was
      compatible with pleomorphic adenoma. To our knowledge, only two cases of
      pleomorphic adenoma arising from the main bronchus have been reported in the
      English-language literature, and ours is the first report of lung-preserving
      surgery.

PMID- 19160013
TI  - Video-assisted thoracoscopic resection for intralobar pulmonary sequestration.
AB  - Video-assisted thoracoscopic treatment of intralobar pulmonary sequestration in
      an obese (120 kg, body mass index 42) young man is described. Two aberrant
      arteries originating from the descending thoracic aorta were transected with a
      vascular stapler, and a left lower lobectomy was successfully performed
      thoracoscopically. Three-dimensional chest computed tomography was used to
      identify the aberrant vessels. Video-assisted thoracoscopic lobectomy is useful
      and minimally invasive for treating pulmonary sequestration, especially in obese
      patients.

PMID- 19160014
TI  - Hepatocellular carcinoma associated with hemorrhaging from iatrogenic rupture of
      a rib metastasis.
AB  - Detecting a rib metastasis as a first manifestation before identifying
      hepatocellular carcinoma (HCC) is rare. We report an HCC with massive bleeding
      from the biopsied rib tumor. A 68-year-old man was referred for right chest pain.
      Computed tomography showed a mass in the rib and two small masses in the liver.
      The biopsied rib continued to bleed, so we removed the entire tumor, including
      the rib. We histologically confirmed the diagnosis as rib metastasis from the
      HCC. The patient died 3 months after the onset. We caution against performing an
      incisional biopsy without due consideration.

PMID- 19160015
TI  - The biological role and regulation of versican levels in cancer.
AB  - Increased expression of the proteoglycan, versican is strongly associated with
      poor outcome for many different cancers. Depending on the cancer type, versican
      is expressed by either the cancer cells themselves or by stromal cells
      surrounding the tumor. Versican plays diverse roles in cell adhesion,
      proliferation, migration and angiogenesis, all features of invasion and
      metastasis. These wide ranging functions have been attributed to the central
      glycosaminoglycan-binding region of versican, and to the N-(G1) and C-(G3)
      terminal globular domains which collectively interact with a large number of
      extracellular matrix and cell surface structural components. Here we review the
      recently identified mechanisms responsible for the regulation of versican
      expression and the biological roles that versican plays in cancer invasion and
      metastasis. The regulation of versican expression may represent one mechanism
      whereby cancer cells alter their surrounding microenvironment to facilitate the
      malignant growth and invasion of several tumor types. A greater understanding of
      the regulation of versican expression may contribute to the development of
      therapeutic methods to inhibit versican function and tumor invasion.

PMID- 19160016
TI  - Targeting group II PAKs in cancer and metastasis.
AB  - The p21 activated kinases (PAKs) play an essential role in cell signaling and
      control a variety of cellular functions including cell motility, survival,
      angiogenesis and mitosis. PAKs are important regulators in growth factor
      signaling, cytoskeletal reorganization and growth factor-mediated cell migration.
      Overexpression of PAKs has been detected in many cancers and linked to increased
      migration potential, anchorage independent growth and metastasis. Six isoforms of
      PAKs are expressed in human and based on their regulatory properties they have
      been classified into group I (PAK1-3) and group II (PAK4-6). Besides the well
      studied group I family, members of the group II PAKs also emerged as interesting
      targets for the development of new inhibitors for cancer therapy. The
      availability of high resolution crystal structures for all group II PAKs and
      their fundamentally different regulatory properties when compared with group I
      enzymes has opened new opportunities for rational drug designing strategies. In
      this review, we summarize the results of recent advances of the function of group
      II PAKs in tumorigenesis and metastasis as well as opportunities for exploring
      the unique catalytic domain dynamics of this protein family for the design of
      group II PAK specific inhibitors.

PMID- 19160017
TI  - Tissue architecture and function: dynamic reciprocity via extra- and intra
      cellular matrices.
AB  - Mammary gland development, functional differentiation, and homeostasis are
      orchestrated and sustained by a balance of biochemical and biophysical cues from
      the organ's microenvironment. The three-dimensional microenvironment of the
      mammary gland, predominantly 'encoded' by a collaboration between the
      extracellular matrix (ECM), hormones, and growth factors, sends signals from ECM
      receptors through the cytoskeletal intracellular matrix to nuclear and chromatin
      structures resulting in gene expression; the ECM in turn is regulated and
      remodeled by signals from the nucleus. In this chapter, we discuss how
      coordinated ECM deposition and remodeling is necessary for mammary gland
      development, how the ECM provides structural and biochemical cues necessary for
      tissue-specific function, and the role of the cytoskeleton in mediating the extra
      -to intracellular dialogue occurring between the nucleus and the
      microenvironment. When operating normally, the cytoskeletal-mediated dynamic and
      reciprocal integration of tissue architecture and function directs mammary gland
      development, tissue polarity, and ultimately, tissue-specific gene expression.
      Cancer occurs when these dynamic interactions go awry for an extended time.

PMID- 19160018
TI  - Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion.
AB  - The Rho subgroup of the Rho GTPases consisting of RhoA, RhoB and RhoC induces a
      specific type of actin cytoskeleton and carry out a variety of functions in the
      cell. mDia and ROCK are downstream effectors of Rho mediating Rho action on the
      actin cytoskeleton; mDia produces actin filaments by nucleation and
      polymerization and ROCK activate myosin to cross-link them for induction of
      actomyosin bundles and contractility. mDia is potentially linked to Rac
      activation and membrane ruffle formation through c-Src-induced phosphorylation of
      focal adhesion proteins, and ROCK antagonizes this mDia action. Thus, cell
      morphogenesis, adhesion, and motility can be determined by the balance between
      mDia and ROCK activities. Though they are not oncogenes by themselves,
      overexpression of RhoA and RhoC are often found in clinical cancers, and RhoC has
      been repeatedly identified as a gene associated with metastasis. The Rho-ROCK
      pathway is implicated in Ras-mediated transformation, the amoeboid movement of
      tumor cells in the three-dimensional matrix, and transmigration of tumor cells
      through the mesothelial monolayer. On the other hand, the Rho-mDia1 pathway is
      implicated in Src-mediated remodeling of focal adhesions and migration of tumor
      cells. There is also an indication that the Rho pathway other than ROCK is
      involved in Src-mediated induction of podosome and regulation of matrix
      metalloproteases. Thus, Rho mediates various phenotypes of malignant
      transformation by Ras and Src through its effectors, ROCK and mDia.

PMID- 19160019
TI  - Characterization of lipophilic drug binding to rat intestinal fatty acid binding
      protein.
AB  - Intestinal fatty acid binding protein (I-FABP) is present at high levels in the
      absorptive cells of the intestine (enterocytes) where it plays a role in the
      intracellular solubilization of fatty acids (FA). However, I-FABP has also been
      shown to bind to a range of non-FA ligands, including some lipophilic drug
      molecules, albeit with generally lower affinity than FA. The significance of
      these lower affinity interactions with exogenous compounds is not known. In this
      manuscript, we describe further characterization of drug-rat I-FABP binding
      interactions using a thermal-shift assay. A structural explanation of the
      observed affinity of rat I-FABP for different drugs based on spectroscopic data
      and modeling experiments is presented. In addition, immunocytochemistry has been
      used to probe the expression of I-FABP in a cell culture model reflective of the
      absorptive cells of the small intestine. Taken together, these data suggest a
      possible role for I-FABP in the disposition of some lipophilic drugs within the
      enterocyte.

PMID- 19160021
TI  - Improvement of cytocompatibility of electrospinning PLLA microfibers by blending
      PVP.
AB  - In this study, microfiber films were used as scaffolds for the purpose of
      vascular tissue engineering. The microfiber films were prepared by
      electrospinning of poly (l-lactide) (PLLA) and polyvinyl pyrrolidone (PVP). PLLA
      and PVP with different ratios were blended with dichloromethane as a spinning
      solvent at room temperature. The properties of the composite microfiber films
      were investigated by differential scanning calorimetry (DSC), scanning electron
      microscopy (SEM) and contact angle measurement. The SEM images showed that the
      morphology of the microfiber films was mainly affected by the weight ratios of
      PLLA/PVP. The DSC results demonstrated that PLLA and PVP mixed uniformly. And the
      hydrophilicity of the films measured increased along with the decrease of the
      PLLA/PVP ratio. Vascular smooth muscle cells (VSMCs) were used to test the
      cytocompatibility. Cell morphology and cell proliferation were measured by SEM,
      laser scanning confocal microscopy (LSCM) and MTT (3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide) assay after 2, 4, 6 days of culture. The
      results indicated that the cell morphology and proliferation on the composite
      films were better than that on the pure PLLA film. Furthermore, morphology and
      proliferation of VSMCs became better with decreasing of the weight ratio of
      PLLA/PVP. In addition, adhesion of platelet on the films was observed by SEM. The
      SEM images showed that the number of adhered platelets decreased with increment
      of PVP content in the films. The electrospinning microfiber composite films of
      PLLA and PVP would have potential use as the scaffolds for vascular tissue
      engineering.

PMID- 19160020
TI  - Preparation of porous 45S5 Bioglass-derived glass-ceramic scaffolds by using rice
      husk as a porogen additive.
AB  - Bioactive glass is currently regarded as the most biocompatible material in the
      bone regeneration field because of its bioactivity, osteoconductivity and even
      osteoinductivity. In the present work porous glass-ceramic scaffolds, which were
      prepared from the 45S5 Bioglass by foaming with rice husks and sintering at 1050
      degrees C for 1 h, have been developed. The produced scaffolds were characterized
      for their morphology, properties and bioactivity. Micrographs taken using a
      scanning electron microscope (SEM) were used for analysis of macropores,
      mesopores and micropores, respectively. The bioactivity of the porous glass
      ceramic scaffolds was investigated using simulated body fluid (SBF) and
      characterized by SEM, energy dispersive spectroscopy (EDS) and X-ray diffraction
      (XRD). A great potential scaffold that provides sufficient mechanical support
      temporarily while maintaining bioactivity, and that can biodegrade at later
      stages is achievable with the developed 45S5 Bioglass-derived scaffolds.

PMID- 19160022
TI  - Hydrogel-magnetic nanoparticles with immobilized L-asparaginase for biomedical
      applications.
AB  - The association of magnetic nanoparticles, which could be controlled by a
      magnetic field and have dimensions which facilitate their penetration in
      cells/tissues, with hydrogel type biopolymeric shells confer them compatibility
      and the capacity to retain and deliver bioactive substances. The main objective
      of this work is the development of a new system based on a biocompatible polymer
      with organic-inorganic structure capable of vectoring support for biologic active
      agents (L: -asparaginase, e.g.). Characterization of size and morphology of the
      hydrogel-magnetic nanoparticles with entrapped L: -asparaginase was made using
      Dynamic Light Scattering method, Transmission Electron Microscopy and Confocal
      Microscopy. The structure of magnetic nanoparticles coated with hydrogel was
      characterized by Fourier Transformed Infrared Spectroscopy. The cytotoxicity of
      nanoparticles was evaluated and also the interactions with microorganisms. We
      obtained hydrogel-magnetic nanoparticles with L: -asparaginase entrapped, with
      sizes below 30 nm in dried stage, capable to penetrate the cells and tissues.

PMID- 19160023
TI  - Injectable biomaterials for minimally invasive orthopedic treatments.
AB  - Biodegradable and injectable hydroxy terminated-poly propylene fumarate (HT-PPF)
      bone cement was developed. The injectable formulation consisting HT-PPF and
      comonomer, n-vinyl pyrrolidone, calcium phosphate filler, free radical catalyst,
      accelerator and radiopaque agent sets rapidly to hard mass with low exothermic
      temperature. The candidate bone cement attains mechanical strength more than the
      required compressive strength of 5 MPa and compressive modulus 50 MPa. The
      candidate bone cement resin elicits cell adhesion and cytoplasmic spreading of
      osteoblast cells. The cured bone cement does not induce intracutaneous irritation
      and skin sensitization. The candidate bone cement is tissue compatible without
      eliciting any adverse tissue reactions. The candidate bone cement is
      osteoconductive and inductive and allow osteointegration and bone remodeling. HT
      PPF bone cement is candidate bone cement for minimally invasive radiological
      procedures for the treatment of bone diseases and spinal compression fractures.

PMID- 19160024
TI  - Stability of prostaglandin E(2) (PGE (2)) embedded in poly-D,L: -lactide-co
      glycolide microspheres: a pre-conditioning approach for tissue engineering
      applications.
AB  - Prostaglandin E(2) (PGE(2)) is involved in angiogenesis, bone repair and
      cartilage metabolism. Thus, PGE(2) might represent a suitable signaling molecule
      in different tissue engineering applications. PGE(2) also has a short half-life
      time. Its incorporation into poly-D: ,L: -lactide-co-glycolide (PLGA)
      microspheres was demonstrated in a previous study. However, the stability of
      bioactive PGE(2) in these microspheres is unknown. With an adjusted mass
      spectrometry assay we investigated the amount of incorporated PGE(2) and the
      stability of PGE(2) in conventional cell culture medium and in PLGA microspheres.
      The stability of PGE(2) was closely pH dependent. Strong acidic or basic
      environments reduced the half-life from 300 h (pH 2.6-4.0) to below 50 h at pH
      2.0 or pH 8.8. The half-life of PGE(2) incorporated into poly-D: ,L: -lactide-co
      glycolide increased drastically to 70 days at 37 degrees C and to 300 days at 8
      degrees C. Analysis with scanning electron microscopy (SEM) and atomic force
      microscopy (AFM) demonstrated a distinct nanostructure of the polymeric phase and
      both nano- and microporosity.

PMID- 19160025
TI  - Tannic acid incorporation in chitosan-based microparticles and in vitro
      controlled release.
AB  - Chitosan, a natural polycationic polysaccharide, was coupled with two polyanionic
      polymers: Na-alginate and carboxymethylcellulose (CMC) and with tannic acid (TA)
      obtaining three species of self-assembled complexes: chitosan/alginate/TA (sample
      1), chitosan/TA (sample 2) and chitosan/CMC/TA (sample 3). The microparticle
      formation was achieved by dropwise addition of one solution into other by using a
      coaxial airflow sprayer. These systems were characterized with regard to particle
      size distribution, thermal stability, tannic acid entrapment efficiency. Sample 2
      showed quite a different behavior compared to the other two samples; the particle
      diameter is located in the nanometric region, the quantity of incorporated tannic
      acid is higher than in the other two samples and the material shows better
      thermal stability. The release of tannic acid from these complexes was studied in
      water (pH = 5.89), phosphates buffer (pH = 7.04) and acetate buffer (pH = 4.11).
      These studies revealed two distinct periods in tannic acid delivery process: an
      initial period, varying between 4 and 10 h, characterized by a high release rate
      with a delivered tannic acid amount of approximately 80% of the incorporated
      polyphenol and a second period, which starts after 20 to 30 h of delivery and it
      ends after approximately 120 h, when the release process takes place with low and
      constant rate and the kinetic curve is linear--characteristic for a zero order
      kinetic.

PMID- 19160026
TI  - Size effect of PLGA spheres on drug loading efficiency and release profiles.
AB  - Drug delivery systems (DDS) based on poly (lactide-co-glycolide) (PLGA)
      microspheres and nanospheres have been separately studied in previous works as a
      means of delivering bioactive compounds over an extended period of time. In the
      present study, two DDS having different sizes of the PLGA spheres were compared
      in morphology, drug (dexamethasone) loading efficiency and drug release kinetics
      in order to investigate their feasibility with regard to production of medical
      combination devices for orthopedic applications. The loaded PLGA spheres have
      been produced by the oil-in-water emulsion/solvent evaporation method following
      two different schemes. Their morphology was assessed by scanning electron
      microscopy and the drug release was monitored in phosphate buffer saline solution
      at 37 degrees C for 550 h using high performance liquid chromatography. The
      synthesis schemes used produced spheres with two different and reproducible size
      ranges (20 +/- 10 and 1.0 +/- 0.4 microm) having a smooth outer surface and
      regular shape. The drug loading efficiency of the 1.0 microm spheres was found to
      be 11% as compared to just 1% for the 20 microm spheres. Over the 550 h release
      period, the larger spheres (diameter 20 +/- 10 microm) released 90% of the
      encapsulated dexamethasone in an approximately linear fashion whilst the
      relatively small spheres (diameter 1.0 +/- 0.4 microm) released only 30% of the
      initially loaded dexamethasone, from which 20% within the first 25 h. The changes
      observed were mainly attributed to the difference in surface area between the two
      types of spheres as the surface texture of both systems was visibly similar. As
      the surface area per unit volume increases in the synthesis mixture, as is the
      case for the 1.0 microm spheres formulation, the amount of polymer-water
      interfaces increases allowing more dexamethasone to be encapsulated by the
      emerging polymer spheres. Similarly, during the release phase, as the surface
      area per unit volume increases, the rate of inclusion of water into the polymer
      increases, permitting faster diffusion of dexamethasone.

PMID- 19160027
TI  - Pharmaceutical research-looking ahead.

PMID- 19160028
TI  - Noninvasive monitoring of HPMA copolymer-RGDfK conjugates by magnetic resonance
      imaging.
AB  - PURPOSE: To evaluate the tumor targeting potential of N-(2
      hydroxypropyl)methacrylamide (HPMA) copolymer-gadolinium(Gd)-RGDfK conjugates by
      magnetic resonance (MR) T1-mapping. METHODS: HPMA copolymers with and without
      RGDfK were synthesized to incorporate side chains for Gd chelation. The
      conjugates were characterized by their side-chain contents and r(1) relaxivity.
      In vitro integrin-binding affinities of polymeric conjugates were assessed via
      competitive cell binding assays on HUVEC endothelial cells and MDA-MB-231 breast
      cancer cells. In vivo MR imaging was performed on MDA-MB-231 tumor-bearing SCID
      mice at different time points using non-targetable and targetable polymers. The
      specificity of alphavbeta3 targeting was assessed by using non-paramagnetic
      targetable polymer to block alphavbeta3 integrins followed by injection of
      paramagnetic targetable polymers after 2 h. RESULTS: The polymer conjugates
      showed relaxivities higher than Gd-DOTA. Endothelial cell binding studies showed
      that IC(50) values for the copolymer with RGDfK binding to alphavbeta3 integrin
      positive HUVEC and MDA-MB-231 cells were similar to that of free peptide.
      Significantly lower T1 values were observed at the tumor site after 2 h using
      targetable conjugate (p < 0.012). In vivo blocking study showed significantly
      higher T1 values (p < 0.045) compared to targetable conjugate. CONCLUSION: These
      results demonstrate the potential of this conjugate as an effective targetable MR
      contrast agent for tumor imaging and therapy monitoring.

PMID- 19160029
TI  - Polymorphisms of PTPN11 coding SHP-2 as biomarkers for ulcerative colitis
      susceptibility in the Japanese population.
AB  - OBJECTIVE: To identify genetic determinants of inflammatory bowel disease (IBD),
      we examined an association between polymorphisms of both the programmed cell
      death 1 gene (PDCD1) and the src homology 2 domain-containing tyrosine
      phosphatase 2 gene (PTPN11) and susceptibility to IBD. METHODS: Study subjects
      comprised 114 patients with ulcerative colitis (UC), 83 patients with Crohn's
      disease, and 200 healthy control subjects. Five single nucleotide polymorphisms
      (SNPs) in PDCD1 and PTPN11 were detected by polymerase chain reaction restriction
      fragment length polymorphism. Subsequently, haplotypes composed of the two SNPs
      in PTPN11 were constructed. RESULTS: The frequencies of the Hap 1 haplotype and
      its homozygous Hap 1/Hap 1 diplotype of PTPN11 were significantly increased in UC
      patients compared to control subjects (P = 0.011 and P = 0.030, respectively).
      While no association was found for PDCD1 for UC or CD and none for PTPN11 for CD.
      CONCLUSION: PTPN11 is a genetic determinant for the pathogenesis of UC, and
      haplotyping of PTPN11 may be useful as a genetic biomarker to identify high-risk
      individuals susceptible to UC.

PMID- 19160030
TI  - Consumers' desire towards current and prospective reproductive genetic testing.
AB  - As our knowledge and abilities in molecular genetics continues to expand, so does
      our ability to detect certain conditions/traits prenatally; however, it is
      unknown if this increase in scientific ability will be utilized by the consumers
      of genetic services. Our study gauges the consumers' opinion towards reproductive
      testing for diseases and enhancements. Prior to their initial visit with a
      genetic counselor, patients were asked to participate in a survey. These
      consumers were asked to indicate traits and conditions for which they would
      choose reproductive genetic testing. The majority of respondents would elect to
      have prenatal genetic testing for mental retardation (75%), deafness (54%),
      blindness (56%), heart disease (52%), and cancer (51%). Our results indicated
      that 49.3% would choose testing for a condition that resulted in death by 5 years
      of age, whereas only 41.1%, 24.9%, and 19% would choose testing for conditions
      that results in death by 20, 40, and 50 years of age, respectively. Most
      respondents did not desire testing for enhancements (e.g. 13% would choose
      testing for superior intelligence). Our study suggests that consumers desire more
      reproductive genetic testing than what is currently offered; however, their
      selection of tests suggests self-imposed limits on testing.

PMID- 19160031
TI  - Epidemiology of atrial fibrillation.
AB  - The incidence and prevalence of atrial fibrillation (AF) increase progressively
      with age, and approximately 50% of patients with AF are 75 years of age or older.
      Advanced age is also a potent risk factor for stroke in patients with AF, and the
      proportion of strokes attributable to AF increases exponentially with age. In
      addition, AF contributes incrementally to health care utilization and costs, and
      decrementally to survival and quality of life in older adults. Furthermore, the
      societal impact of AF will likely double over the next three decades due to the
      aging of the population. For these reasons, it is essential to develop more
      effective strategies for the prevention and treatment of AF in older individuals.

PMID- 19160032
TI  - More clinical lessons from the FIELD study.
AB  - INTRODUCTION: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD)
      Study investigated the effect of fenofibrate treatment in 9,795 patients with
      type 2 diabetes. RESULTS AND DISCUSSION: Reduction in major coronary events (the
      primary endpoint) and total cardiovascular disease (CVD) events (the secondary
      endpoint) was similar (relative risk reduction 11%), but only significant for
      total CVD events (p = 0.035). The benefit of fenofibrate treatment was greater in
      patients with mixed dyslipidaemia, especially in those with triglycerides >2.3
      mmol/L and low plasma levels of high-density lipoprotein cholesterol (relative
      risk reduction 27%, p = 0.005). There were also microvascular benefits associated
      with fenofibrate treatment, specifically reduction in the rate of laser therapy
      for retinopathy (by 30%, p < 0.001), non-traumatic amputation (by 38%, p = 0.011)
      and progression of albuminuria (p < 0.002). Fenofibrate was generally well
      tolerated alone or in combination with a statin. CONCLUSIONS: Overall, the FIELD
      study data support the use of fenofibrate for CVD prevention in diabetes, ideally
      in patients without prior macrovascular or microvascular complications.
      Fenofibrate may also have a role as a preventive treatment for diabetic
      retinopathy. Addition of fenofibrate to statin therapy may a logical progression
      from the FIELD study data, although the efficacy and tolerability of this
      approach needs to be evaluated in prospective outcome studies.

PMID- 19160033
TI  - Barebacking: a review of the literature.
AB  - This article synthesizes the peer-reviewed literature about barebacking, an HIV
      risk behavior that is generally understood as intentional unprotected anal
      intercourse between men where HIV transmission is a possibility. Of the 42
      academic reports identified in the Anglophone literature, the greatest attention
      is given to U.S. publications and empirical projects. The variable nomenclature
      about barebacking is recognized and it is concluded that although epidemiological
      data suggest prevalence of barebacking varies across regions, time, and
      serostatus, the majority of men who have sex with men (MSM) do not intentionally
      seek out condomless anal sex. Findings show that macro-, meso-, interpersonal-,
      and intrapersonal level factors, such as homonegativity, community norms, partner
      intimacy, and drug use, converge to influence the likelihood that an individual
      will bareback. A conceptual framework to examine the reciprocal and dynamic
      relationships sustaining barebacking is proposed. In examining the theoretical
      and methodological limitations of the research about barebacking, the
      atheoretical nature of the studies, failure to report analyses conducted, and
      suboptimal measures are included among the study constraints. Furthermore, in
      research to date, the majority of participants have been white, urban, and gay
      identified; thus, more research is needed to capture the viewpoints of diverse
      MSM communities. There has also been an overly individualistic focus on
      barebacking which needs to be tempered by greater consideration of the impact of
      macro- and meso-level factors upon MSM's behavior. With respect to programmatic
      responses, more culturally bound strategies are called for.

PMID- 19160034
TI  - Comparing internet-based and venue-based methods to sample MSM in the San
      Francisco Bay Area.
AB  - Methods of collecting behavioral surveillance data, including Web-based methods,
      have recently been explored in the United States. Questions have arisen as to
      what extent Internet recruitment methods yield samples of MSM comparable to those
      obtained using venue-based recruitment methods. We compare three recruitment
      methods among MSM with respect to demographic and risk behaviors, one sample was
      obtained using time location sampling at venues in San Francisco, one using a
      venue based like approach on the Internet and one using direct-marketing
      advertisements to recruit participants. The physical venue approach was most
      successful in completing interviews with approached men than both Internet
      approaches. Respondents recruited via the three methods reported slight
      differences in risk behavior. Direct marketing internet recruitment can obtain
      large samples of MSM in a short time.

PMID- 19160035
TI  - Evidence based interventions for preventing HIV transmission: commentary on
      Rotheram-Borus et al. (2009).

PMID- 19160037
TI  - Hox genes in the parasitic platyhelminthes Mesocestoides corti, Echinococcus
      multilocularis, and Schistosoma mansoni: evidence for a reduced Hox complement.
AB  - Little is known about the Hox gene complement in parasitic platyhelminthes
      (Neodermata). With the aim of identifying Hox genes in this group we performed
      two independent strategies: we performed a PCR survey with degenerate primers
      directed to the Hox homeobox in the cestode Mesocestoides corti, and we searched
      genomic assemblies of Echinococcus multilocularis and Schistosoma mansoni. We
      identified two Hox genes in M. corti, seven in E. multilocularis, and nine in S.
      mansoni (including five previously reported). The affinities of these sequences,
      and other previously reported Hox sequences from flatworms, were determined
      according to phylogenetic analysis, presence of characteristic parapeptide
      sequences, and unusual intron positions. Our results suggest that the last common
      ancestor of triclads and neodermatans had a Hox gene complement of at least seven
      genes, and that this was probably derived by gene loss from a larger ancestral
      Hox complement in lophotrochozoans.

PMID- 19160038
TI  - A comparative analysis of molecular diversity of erect Milkvetch (Astragalus
      adsurgens) germplasm from north China using RAPD and ISSR markers.

PMID- 19160039
TI  - On the diversity of the laccase gene: a phylogenetic perspective from
      Botryosphaeria rhodina (Ascomycota: Fungi) and other related taxa.
AB  - The present study is the first describing the sequencing of a fragment of the
      copper-oxidase domain of a laccase gene in the family Botryosphaeriaceae. The aim
      of this work was to assess the degree of genetic and evolutionary relationships
      of a laccase gene from Botryosphaeria rhodina MAMB-05 with other ascomycete and
      basidiomycete laccase genes. The 193-amino acid sequences of the copper-oxidase
      domain from several different fungi, insects, a plant, and a bacterial species
      were retrieved from GenBank and aligned. Phylogenetic analyses were performed
      using neighbor-joining, maximum parsimony, and Bayesian inference methods. The
      organisms studied clustered into five gene clades: fungi (ascomycetes and
      basidiomycetes), insects, plants, and bacteria. Also, the topologies showed that
      fungal laccases of the ascomycetes and basidiomycetes are clearly separated into
      two distinct clusters. This evidence indicated that B. rhodina MAMB-05 and other
      closely related ascomycetes are a new biological resource given the
      biotechnological potential of their laccase genes.

PMID- 19160040
TI  - Adaptation and psychometric evaluation of the multidimensional scale of perceived
      social support for Arab American adolescents.
AB  - The multidimensional scale of perceived social support (MSPSS) was revised for
      Arab American adolescents (MSPSS-AA). Items measuring social support from
      significant others were omitted and items measuring support from school personnel
      were added based on advice from cultural experts. The sample consisted of 635
      Arab American young adolescents in metropolitan Detroit. Confirmatory factor
      analysis (CFA) supported the proposed three-factor solution (family, friends, and
      school personnel). Internal consistency coefficients for the three subscales of
      family (alpha = 0.63), friends (alpha = 0.75), school personnel (alpha = 0.72)
      were good. As predicted, perceived support from family, friends, and school
      personnel were inversely related to self reports of daily hassles and
      internalizing behavior and positively related to assistance seeking coping, which
      provides evidence for construct validity. Support for discriminant validity was
      also demonstrated with significantly larger correlations between the MSPSS-AA
      Family subscale and daily hassles specific to parents and the MSPSS-AA Friend
      subscale and daily hassles specific to peers. These finding suggest that the
      MSPSS-AA is reliable and valid for use with Arab-American adolescents.

PMID- 19160041
TI  - Ulcerative gastritis secondary to Epstein-Barr viral infection.

PMID- 19160042
TI  - Nitroglycerin in the prevention of post-ERCP pancreatitis: a meta-analysis.
AB  - The objective of this research paper is to evaluate the effect of prophylactic
      nitroglycerin in the prevention of post-endoscopic retrograde
      cholangiopancreatography (ERCP) pancreatitis (PEP) by performing a meta-analysis
      of randomized controlled trials (RCTs). Electronic databases, including PubMed,
      EMBASE, the Cochrane library, and the Science Citation Index, were searched to
      retrieve relevant trials. Outcome measures were the incidence of PEP. Four RCTs,
      enrolling a total of 856 patients, were included. Meta-analysis of these trials
      indicated a significant association between the use of nitroglycerin and the
      reduction of PEP (RR 0.60; 95%CI: 0.39-0.92; P = 0.02). However, subsequent
      sensitive analysis failed to confirm that nitroglycerin was statistically
      superior to a placebo in reducing PEP (RR 0.68; 95%CI: 0.41-1.11; P = 0.12).
      Based on the limitations in this meta-analysis, prophylactic use of
      nitroglycerine for all patients who underwent ERCP is not recommended. Further
      clinical trials are required to confirm the effect of nitroglycerin in the
      prevention of PEP.

PMID- 19160043
TI  - Risk factors for gastrointestinal ulcer disease in the US population.
AB  - PURPOSE: Gastrointestinal (GI) ulcers are frequently seen in patients with
      multiple chronic medical conditions. Few studies have described the overall
      prevalence, comorbidities, or risk factors associated with this diagnosis. We
      sought to determine among a national dataset if individuals with certain medical
      comorbidities are at increased risk for gastrointestinal ulcer disease, while
      controlling for relevant confounders. RESULTS: The overall prevalence of GI ulcer
      is 8.4%. A significant increased risk of ulcer history is associated with older
      age (OR 1.67), African-Americans (OR 1.20) current (OR 1.99) and former (OR 1.55)
      tobacco use, former alcohol use (OR 1.29), obesity (OR 1.18), chronic obstructive
      pulmonary disease (OR 2.34), chronic renal insufficiency (OR 2.29), coronary
      heart disease (OR 1.46), and three or more doctor visits in a year (OR 1.49).
      CONCLUSIONS: This large US population-based study reports on a number of
      demographic, behavioral, and chronic medical conditions associated with higher
      risk of gastrointestinal ulcer disease.

PMID- 19160044
TI  - Infection by CagA-positive Helicobacter pylori strains may contribute to alter
      the sperm quality of men with fertility disorders and increase the systemic
      levels of TNF-alpha.
AB  - This study was aimed to address the possibility that Helicobacter pylori
      infection may play a detrimental role in semen quality of men with idiopathic
      infertility. Infection by H. pylori and by strains expressing CagA was determined
      in 80 male infertile patients by Western blotting and ELISA. Semen analysis was
      performed by light microscopy and transmission electron microscopy quantitatively
      elaborated (fertility index, immaturity, necrosis, and apoptosis percentages).
      Systemic levels of IL-6 and TNF-alpha were evaluated. Infertile patients infected
      with H. pylori showed a low sperm quality respective to uninfected patients.
      Particularly, in CagA-positive patients we observed a significant reduction in
      sperm motility and in the fertility index, while apoptosis and necrosis were
      increased. In these patients, the means of systemic TNF-alpha levels were higher
      than those of uninfected patients. The negative influence of CagA-positive H.
      pylori infection on sperm quality may help to understand the role of chronic
      infections in reproductive disorders.

PMID- 19160045
TI  - Effects of Helicobacter pylori infection on the expressions of Bax and Bcl-2 in
      patients with chronic gastritis and gastric cancer.
AB  - The aim of the present study is to evaluate the influence of Helicobacter pylori
      on Bax and Bcl-2 mRNA and protein levels in patients with chronic gastritis and
      gastric cancer. The study included 217 patients, of which 26 were uninfected; 127
      had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer.
      Bacterial genotypes were evaluated by PCR, and the expression values were
      determined by quantitative real-time PCR and immunohistochemistry. Our data
      showed that the up-regulationary effects of H. pylori infection on the pro
      apoptotic gene, Bax, were stronger than its induction of Bcl-2; this effect may
      increase apoptosis in patients with chronic gastritis. In patients with gastric
      cancer, the up-regulation of the anti-apoptotic gene, Bcl-2, counteracted the pro
      apoptotic effects of Bax, leading to a deregulation of apoptosis-associated gene
      expression, favoring cell proliferation. Thus, the disturbance in Bax and Bcl-2
      balance, induced by H. pylori, might be important in gastric cancer development.

PMID- 19160046
TI  - Food intolerance, diet composition, and eating patterns in functional dyspepsia
      patients.
AB  - The aims of this study are to investigate dietary factors, food intolerance, and
      the body mass index data, as an indicator of nutritional status, in functional
      dyspepsia patients. Forty-one functional dyspepsia patients and 30 healthy
      volunteers answered a standardized questionnaire to identify eating habits and
      food intolerance, and then completed a 7-day alimentary diary. There was no
      significant difference in daily total caloric intake between patients and
      controls. Patients associated their symptoms with the ingestion of several foods,
      but in general maintained their regular intake, with the exception of a small
      reduction in the proportion of fat in comparison with controls (median 28 vs.
      34%; P = 0.001). No patient was underweight. In conclusion, our results suggest
      that food intolerance has no remarkable influence on food pattern and nutritional
      status in most functional dyspepsia patients. Further studies are necessary to
      clarify the role of fat in the generation of dyspeptic symptoms.

PMID- 19160047
TI  - Characteristics and interactions of Helicobacter pylori and H. pylori-infected
      human gastroduodenal epithelium in peptic ulcer: a transmission electron
      microscopy study.
AB  - Helicobacter pylori (H. pylori) has been presumed to be an initiating factor in a
      previously recognized chain of events, starting with active chronic gastritis and
      leading to atrophy of the mucosal membrane, intestinal metaplasia, dysplasia
      (intraepithelial neoplasia), and finally culminating in gastric carcinoma.
      Adherence of H. pylori to the gastroduodenal epithelium is believed to be an
      important step in the induction of active chronic inflammation of the mucosal
      layer. However, it is not clear how the pathogen chronically colonizes the
      gastroduodenal epithelium. In this study, 30 biopsy specimens from H. pylori
      positive peptic ulcer (15 for gastric ulcer, 15 for duodenal ulcer) patients were
      examined by transmission electron microscopy (TEM) to observe the structural
      adherence of H. pylori to gastroduodenal epithelium while ten healthy postulants
      were served as controls. We also investigated the interaction between H. pylori
      and gastroduodenal epithelial cells. Morphological appearances of both the
      pathogen and the cells as well as features of colonization, attachment, and
      internalization were observed. H. pylori exhibited both spiral and coccoid forms.
      Cytoplasmic vacuolar degeneration played by the vacuolating toxin (VacA) was
      apparent in gastroduodenal epithelial cells. Specially, a number of tumor cells
      were found in H. pylori-positive gastric intestinal metaplasia (IM) mucosa under
      TEM which provided an ultrastructural evidence of IM carrying a particularly high
      risk for the development of gastric cancer.

PMID- 19160048
TI  - A resident or fellow's dilemma: a medically incorrect order by a direct clinical
      supervisor.
AB  - The relative medicolegal responsibilities of residents or fellows versus
      attendings in the care of service patients have been well studied, but the
      subject of how a resident or fellow can protest or refuse an order believed to be
      medically wrong or contraindicated is unstudied and unknown. Two cases are
      reported in which a gastroenterology fellow was ordered by an attending to
      perform or assist in invasive procedures believed to be either contraindicated
      because of patient instability or unambiguously not indicated according to
      established procedure guidelines. These two novel cases highlight the dilemma
      encountered by a resident or fellow with regard to obeying an improper order to
      avoid complaining about an attending versus disobeying such an order to comply
      with the Hippocratic Oath of doing no harm. Although the reported cases involved
      gastroenterology fellows, this type of problem can occur during any medical
      residency or fellowship. These case reports suggest the need for a hospital-based
      administrative policy and mechanism to resolve such conflicts fairly, without
      confrontation, resident intimidation, or career consequences.

PMID- 19160049
TI  - Endoscopic hemostasis in nonvariceal upper gastrointestinal bleeding: comparison
      of physician practice in the East and the West.
AB  - BACKGROUND: Endoscopic hemostasis is commonly practiced during GI endoscopy
      practice. We hypothesized that, because the choice of endoscopic intervention is
      influenced by many factors, for example personal experience, prior training,
      guidelines, etc., there would be differences in practice patterns among different
      groups of endoscopists. OBJECTIVE: To explore the potentially different practices
      for endoscopic hemostasis between the "East" (eight Asian countries) and the
      "West" (USA and Canada). DESIGN: Cross-sectional descriptive study (internet
      based survey). STUDY SUBJECTS: We administered a questionnaire survey to American
      Society of Gastrointestinal Endoscopy (ASGE) and Korean Society of
      Gastroenterology (KSGE) members (see:
      http://www4.utsouthwestern.edu/inetdemo/endoscopy/hemostasis.html , or
      supplementary paper for review online). RESULTS: Eastern ASGE members (n = 112)
      were more likely to complete this survey than ASGE members in the West (n = 180):
      15.1 vs. 5.0%, P < 0.001. Choice of hemostatic method, regardless of primary or
      recurrent bleeding, varied significantly among Eastern and Western endoscopists.
      For example, for treatment of a gastric ulcer with a visible vessel, a vast
      majority (70%) of Western endoscopists preferred pre-injection followed by
      thermocoagulation whereas responses from the East were more diverse, with
      endoclip application +/- pre-injection being the top choice (29%) (P < 0.001).
      Personal EGD volume and hospital bed numbers did not seem to be associated with
      hemostatic choices in either the East or the West. CONCLUSIONS: Endoscopic
      hemostasis practice patterns for upper GI tract bleeding differed among Eastern
      and Western endoscopists, suggesting fundamental differences in practice habit
      determinants.

PMID- 19160050
TI  - Serum levels of high-sensitivity C-reactive protein (hs-CRP)in Helicobacter
      pylori-infected peptic ulcer patients and its association with bacterial CagA
      virulence factor.
AB  - OBJECTIVE: CRP is a marker of inflammation and infection of the gastric mucosa
      with Helicobacter pylori, which causes an inflammatory reaction. It has been
      reported that CagA(+) H. pylori strains induce more severe gastric inflammation
      and are also associated with higher risks of peptic ulcer and gastric cancer. The
      purpose of this study was to compare serum concentrations of hs-CRP in H. pylori
      infected peptic ulcer (PU) patients, H. pylori infected asymptomatic (AS)
      carriers, and a healthy control group, and their association with bacterial
      virulence factor CagA. MATERIAL AND METHODS: A total of 60 H. pylori infected PU
      patients (30 patients were positive for anti-CagA antibody and 30 were negative
      for anti-CagA antibody), 53 H. pylori-infected AS carriers (25 subjects were
      positive for anti-CagA antibody and 28 were negative for anti-CagA antibody), and
      22 healthy H. pylori-negative subjects (as a control group) were enrolled in the
      study. Serum concentrations of hs-CRP were measured by use of an ELISA method.
      RESULTS: The mean serum level of hs-CRP in all PU patients (124.9+/-32.4 MUg/dl)
      was significantly higher than that in all AS subjects (18.6+/-2.6 MUg/dl;
      P<0.001) and the healthy uninfected control group (10.7+/-2.9 MUg/dl; P<0.0001).
      Moreover, the mean serum level of hs-CRP in the AS group was significantly higher
      than that observed in the uninfected control group (P<0.04). No significant
      difference was observed between mean serum levels of hs-CRP of PU patients with
      positive test for anti-CagA antibody (132.6+/-49.4 MUg/dl) and PU patients with
      negative test for anti-CagA antibody (117.1+/-42.9 MUg/dl). Moreover, mean serum
      levels of hs-CRP were similar in AS subjects with positive test for anti-CagA
      (18.4+/-3.1 MUg/dl) and in those who were negative for anti-CagA antibody (18.9+/
      4.1 MUg/dl). CONCLUSION: The results of this study showed that mean serum
      concentrations of hs-CRP in PU patients and in H. pylori infected AS carriers
      were higher than in a healthy control group. Although H. pylori infection is
      associated with higher serum levels of hs-CRP, serum concentrations of this
      inflammatory marker were not affected by expression of bacterial CagA virulence
      factor.

PMID- 19160051
TI  - Ileal mucosal and fecal pancreatitis associated protein levels reflect severity
      of salmonella infection in rats.
AB  - BACKGROUND: Microbial infections induce ileal pancreatitis-associated
      protein/regenerating gene III (PAP/RegIII) mRNA expression. Despite increasing
      interest, little is known about the PAP/RegIII protein. Therefore, ileal mucosal
      PAP/RegIII protein expression, localization, and fecal excretion were studied in
      rats upon Salmonella infection. RESULTS: Salmonella infection increased ileal
      mucosal PAP/RegIII protein levels in enterocytes located at the crypt-villus
      junction. Increased colonization and translocation of Salmonella was associated
      with higher ileal mucosal PAP/RegIII levels and secretion of this protein in
      feces. CONCLUSIONS: PAP/RegIII protein is increased in enterocytes of the ileal
      mucosa during Salmonella infection and is associated with infection severity.
      PAP/RegIII is excreted in feces and might be used as a new and non-invasive
      infection marker.

PMID- 19160053
TI  - Population-based prevention of child maltreatment: the U.S. Triple p system
      population trial.
AB  - The prevention of child maltreatment necessitates a public health approach. In
      the U.S. Triple P System Population Trial, 18 counties were randomly assigned to
      either dissemination of the Triple P-Positive Parenting Program system or to the
      services-as-usual control condition. Dissemination involved Triple P professional
      training for the existing workforce (over 600 service providers), as well as
      universal media and communication strategies. Large effect sizes were found for
      three independently derived population indicators: substantiated child
      maltreatment, child out-of-home placements, and child maltreatment injuries. This
      study is the first to randomize geographical areas and show preventive impact on
      child maltreatment at a population level using evidence-based parenting
      interventions.

PMID- 19160052
TI  - A 10-year follow-up of a longitudinal study of gallstone prevalence at necropsy
      in South East England.
AB  - The purpose of this study was to examine a previous increase in male gallstone
      disease and to consider the burden of gallstones in a necropsy study with matched
      controls over a decade. Gallstone prevalence in 5,050 males fell from 20.2% to
      19.1% (P=0.022) and in 4,125 females fell from 30.4% to 29.0% (P=0.03). Female
      gallstone subjects had a higher BMI than controls 24.5 vs. 23.3 (P<0.01), but
      males did not. Gallstones were twice as common in diabetics, but not with
      coronary heart disease (CHD). A third of elderly patients of both sexes had
      gallstones, but cholecystectomy was more common in females, 17:10%. Gallstone
      related mortality was 0.7%. The prevalence of gallstones fell slightly. The
      association between gallstones and diabetes was confirmed, but not for CHD, and
      for BMI this was confined to females. Gallstones are very common in the elderly,
      but most are unoperated and seldom cause death.

PMID- 19160054
TI  - Hemodynamic analysis of microcirculation in malaria infection.
AB  - Malaria-infected red blood cells (IRBCs) show various changes in mechanical
      properties. IRBCs lose their deformability and develop properties of
      cytoadherence and rosetting. To clarify how these changes advance microvascular
      occlusion, we need qualitative and quantitative information on hemodynamics in
      malaria infection, including the interaction among IRBCs, healthy RBCs, and
      endothelial cells. We developed a numerical model of blood flow with IRBCs based
      on conservation laws of fluid dynamics. The deformability and adhesive property
      of IRBCs were simply modeled using springs governed by Hook's law. Our model
      could express the basic behavior of IRBCs, including the rolling motion due to
      cytoadhesive interaction with endothelial cells and complex interaction with
      healthy RBCs. We confirmed that these types of interactions significantly
      increase the flow resistance, particularly when knobs develop.

PMID- 19160057
TI  - Variation in cytosine methylation patterns during ploidy level conversions in
      Eragrostis curvula.
AB  - In many species polyploidization involves rearrangements of the progenitor
      genomes, at both genetic and epigenetic levels. We analyzed the cytosine
      methylation status in a 'tetraploid-diploid-tetraploid' series of Eragrostis
      curvula with a common genetic background by using the MSAP (Methylation-sensitive
      Amplified Polymorphism) technique. Considerable levels of polymorphisms were
      detected during ploidy conversions. The total level of methylation observed was
      lower in the diploid genotype compared to the tetraploid ones. A significant
      proportion of the epigenetic modifications occurring during the tetraploid
      diploid conversion reverted during the diploid-tetraploid one. Genetic and
      expression data from previous work were used to analyze correlation with
      methylation variation. All genetic, epigenetic and gene expression variation data
      correlated significantly when compared by pairs in simple Mantel tests.
      Dendrograms reflecting genetic, epigenetic and expression distances as well as
      principal coordinate analysis suggested that plants of identical ploidy levels
      present similar sets of data. Twelve (12) different genomic fragments displaying
      different methylation behavior during the ploidy conversions were isolated,
      sequenced and characterized.

PMID- 19160056
TI  - Genome-wide analysis of gene expression profiles during ear development of maize.
AB  - In order to unravel the molecular mechanism of maize ear development, a
      microarray containing approximately 56,000 probes was used to monitor the gene
      expression profiles of ears at four developmental stages. The results showed that
      2,794 genes, accounting for 5.0% of the total probes, changed significantly
      during ear development. Among the 2,794 genes, 1,844 genes differentially
      expressed during the spikelet differentiation phase, 836 genes during the floret
      primordium differentiation phase and 645 genes during the floret organ
      differentiation phase. Hierarchical clustering revealed that the differentially
      expressed genes had 9 major expression patterns. Based on Mips Functional
      Catalogue, 684 differentially expressed genes were grouped into at least one
      functional category, including metabolism (30.4%), protein related function
      (29.2%), biogenesis of cellular components (15.4%) and transcription (13.7%). The
      analysis revealed that the auxin signaling pathway play an important role in ear
      development. Moreover, regulation of some transcription factors may play a key
      role during ear development. RT-PCR and in situ hybridization for some selected
      genes validated our microarray data and supplied additional information on ear
      developmental processes.

PMID- 19160058
TI  - Association mapping of agronomic traits on chromosome 2A of wheat.
AB  - Association mapping is a method to test the association between molecular markers
      and quantitative trait loci (QTL) based on linkage disequilibrium (LD). In this
      study, the collection of 108 wheat germplasm accessions form China were evaluated
      for their plant heights, spike length, spikelets per spike, grains per spike,
      thousand kernel weight and spikelets density in 3 years at three locations. And
      they were genotyped with 85 SSR markers and 40 EST-SSR markers. The population
      structure was inferred on the basis of unlinked 48 SSR markers and 40 EST-SSR
      markers. The extent of LD on chromosome 2A was 2.3 cM. Association of 37 SSR loci
      on chromosomes 2A with six agronomic traits was analysed with a mixed linear
      model. A total of 14 SSR loci were significantly associated with agronomic
      traits. Some of the associated markers were located in the QTL region detected in
      previous linkage mapping analysis. Our results demonstrated that association
      mapping can enhance QTL information and achieves higher resolution with short LD
      extent.

PMID- 19160059
TI  - Human hair mercury levels in the Wanshan mercury mining area, Guizhou Province,
      China.
AB  - The total mercury (T-Hg) and methyl mercury (Me-Hg) concentrations in the hair
      were measured to evaluate mercury (Hg) exposure for the residents in Da-shui-xi
      Village (DSX) and Xia-chang-xi Village (XCX) in the Wanshan Hg mining area,
      Guizhou Province, Southwestern China. The mean concentrations in the hair of DSX
      residents were 5.5 +/- 2.7 MUg/g and 1.9 +/- 0.9 MUg/g for T-Hg and Me-Hg,
      respectively. The concentrations in the hair of XCX residents were 3.3 +/- 1.4
      MUg/g and 1.2 +/- 0.5 MUg/g for T-Hg and Me-Hg, respectively. Hair Me-Hg
      concentrations were significantly correlated to T-Hg (r = 0.42, P < 0.01) in the
      two sites; on average, hair Me-Hg concentration accounted for 40 and 44% of T-Hg
      for DSX and XCX residents, respectively. Age has no obvious correlation with hair
      Hg and the hair Hg levels showed a significant gender difference, with higher T
      Hg and Me-Hg concentrations in the hair from males than females. The rice
      collected from the two sites showed high levels of T-Hg and Me-Hg concentration.
      The results indicated a certain Hg exposure for the residents in DSX and XCX in
      the Wanshan Hg mining area.

PMID- 19160061
TI  - Inert dusts and their effects on the poultry red mite (Dermanyssus gallinae).
AB  - The haematophagous poultry red mite (Dermanyssus gallinae) is the most important
      pest of egg laying hens in many parts of the world. Control has often relied on
      chemical pesticides, but inert dusts, which are thought to kill target hosts
      primarily by desiccation, have become one of the most commonly applied
      alternative control methods for poultry red mite in Europe. This development has
      occurred despite a lack of knowledge of the efficacy of the different types of
      inert dusts and how this is affected by environmental parameters, e.g. the high
      relative humidity found in poultry houses. In this laboratory study the efficacy
      of different commercial inert dust products against D. gallinae is compared. All
      tested compounds killed mites, but there was a clear ranking of efficacy
      (measured as weight loss after 24 h and as time until 50% mortality),
      particularly at 75% relative humidity (RH). At 85% RH the efficacy was
      significantly lower for all tested compounds (P < 0.001). Weight changes over
      time followed an exponential evaporation model until the mites started dying
      whereafter the rate of evaporation increased again and followed a slightly
      different exponential evaporation model. A tarsal test showed that 24 h exposure
      to surfaces treated with doses much lower than those recommended by the producers
      is sufficient to kill mites as fast as when they were dusted with massive doses.
      These data emphasise the need for thorough treatment of all surfaces in a poultry
      house in order to combat D. gallinae.

PMID- 19160060
TI  - Prevalence and key figures for the poultry red mite Dermanyssus gallinae
      infections in poultry farm systems.
AB  - Recent surveys and sample collection have confirmed the endemicity of Dermanyssus
      gallinae in poultry farming worldwide. The reduction in number and efficacy of
      many acaricide products has accentuated the prevalence rates of this poultry
      ectoparasite observed more often in non intensive systems such as free-range,
      barns or backyards and more often in laying hens than in broiler birds. The lack
      of knowledge from producers and the utilisation of inadequate, ineffective or
      illegal chemicals in many countries have been responsible for the increase in
      infestation rates due to the spread of acaricide resistance. The costs for
      control methods and treatment are showing the tremendous economic impact of this
      ectoparasite on poultry meat and egg industries. This paper reviews the
      prevalence rates of this poultry pest in different countries and for different
      farming systems and the production parameters which could be linked to this pest
      proliferation.

PMID- 19160062
TI  - Molecular phylogenetic assessment of host range in five Dermanyssus species.
AB  - Given that 14 out of the 25 currently described species of Dermanyssus Duges,
      1834, are morphologically very close to each another, misidentifications may
      occur and are suspected in at least some records. One of these 14 species is the
      red fowl mite, D. gallinae (De Geer, 1778), a blood parasite of wild birds, but
      also a pest in the poultry industry. Using molecular phylogenetic tools we aimed
      to answer two questions concerning host specificity and synanthropicity: (1) is
      D. gallinae the only species infesting European layer farms?, and (2) can
      populations of D. gallinae move from wild to domestic birds and vice versa?
      Mitochondrial cytochrome oxidase I gene sequences were obtained from 73
      Dermanyssus populations collected from nests of wild European birds and from
      poultry farms and these were analyzed using maximum parsimony and Bayesian
      inference. Mapping of the observed host range on the obtained topology and
      correlation with behavioural observations revealed that (1) host range is
      strongly dependent on some ecological parameters (e.g. nest hygiene, exposure to
      pesticides and predators), that (2) out of five species under test, synanthropic
      populations were found only in lineages of D. gallinae, and that (3) at least
      some haplotypes found in wild birds were very close to those found in association
      with domestic birds.

PMID- 19160063
TI  - Asymmetric reproductive interference between two closely related spider mites:
      Tetranychus urticae and T. turkestani (Acari: Tetranychidae).
AB  - Tetranychus turkestani Ugarov and Nikolskii and Tetranychus urticae Koch RF (red
      form) (Acari: Tetranychidae) are closely related species. Previously, the two
      species were found in separate agricultural habitats in Israel. Here, additional
      collections were undertaken and mixed populations of the two species were found.
      Manipulation experiments were conducted in order to test whether sexual
      interactions occur when T. turkestani and T. urticae RF share the same host.
      Interspecific crosses showed that the two species are capable of producing viable
      F(1) females, but that these females are sterile as their F(2) eggs failed to
      hatch. This indicates a post-zygotic reproductive barrier, supporting the current
      placement of T. turkestani as a separate taxon. Mating behavior parameters
      revealed that males of both species courted virgin conspecific and heterospecific
      females at the same rate and readily tried to copulate with them. Female mate
      recognition seemed to be more reliable in T. turkestani than in T. urticae RF as
      the number of copulations was significantly higher and their duration
      significantly shorter in the T. turkestani interspecific (T. turkestani female x
      T. urticae RF male) as compared to the intraspecific crosses, a phenomenon not
      observed in T. urticae RF. In mixed cultures, a significant reduction in female
      production was observed for T. urticae RF but not for T. turkestani, suggesting
      an asymmetric reproductive interference effect in favor of T. turkestani. The
      long term outcome of this effect is yet to be determined since additional
      reproductive factors such as oviposition rate and progeny survival to adulthood
      may reduce the probability of demographic displacement of one species by the
      other in overlapping niches.

PMID- 19160064
TI  - Caveolin-1 overexpression correlates with tumour progression markers in
      pancreatic ductal adenocarcinoma.
AB  - The assessment of caveolin-1 (Cav-1) as a marker of tumor aggressiveness in
      pancreatic ductal adenocarcinoma (PDAC). In this study, we examined the
      expression of Cav-1 in 34 human PDAC tissue samples and the associated
      peritumoral tissues by immunohistochemistry and western blot. Additionally, we
      correlated Cav-1 expression with other tissue (Ki-67, p53) and serum (CA 19-9)
      tumor markers. In the tumor-derived tissue, both tumor cells and blood vessels
      expressed Cav-1. In contrast, in peritumoral tissue, Cav-1 expression was
      confined mainly to blood vessels and was only occasionally expressed in ductal or
      parenchymal cells. Western blot analysis confirmed the overexpression of Cav-1 in
      pancreatic tumors compared with peritumoral tissue. Cav-1 expression in tumor
      tissues was correlated with both the Ki-67 LI (r = 0.95, P < 0.0001) and p53
      expression (chi2 = 9.91, P < 0.005). Overexpression of Cav-1 was associated with
      tumor size, grade and stage and Cav-1 expression in tumors was correlated with an
      increased serum level of CA 19-9 (r = 0.795, P < 0.001). Based on the results of
      this study, the inclusion of Cav-1 in a putative panel of biomarkers predicting
      pancreatic cancer aggressiveness is warranted.

PMID- 19160065
TI  - Lipocalin-2: pro- or anti-apoptotic?
AB  - Survival and apoptosis signaling pathways are altered concomitantly in response
      to numerous endogenous and exogenous stressors. The lipocalin family of small
      soluble proteins has been implicated in modulating apoptosis. However, the
      overall effect of these proteins has been variable, showing both pro- and anti
      apoptotic activities. The goal of this minireview is to summarize the studies on
      lipocalins and apoptosis and consider what roles lipocalin-2 may play in cell
      death and survival.

PMID- 19160066
TI  - Auto-excision of selectable marker genes from transgenic tobacco via a stress
      inducible FLP/FRT site-specific recombination system.
AB  - Antibiotic resistance marker genes are powerful selection tools for use in plant
      transformation processes. However, once transformation is accomplished, the
      presence of these resistance genes is no longer necessary and can even be
      undesirable. We herein describe the successful excision of antibiotic resistance
      genes from transgenic plants via the use of an oxidative stress-inducible FLP
      gene. FLP encodes a recombinase that can eliminate FLP and hpt selection genes
      flanked by two FRT sites. During a transformation procedure in tobacco,
      transformants were obtained by selection on hygromycin media. Regenerants of the
      initial transformants were screened for selective marker excision in hydrogen
      peroxide supplemented media and both the FLP and hpt genes were found to have
      been eliminated. About 13-41% of regenerated shoots on hydrogen peroxide media
      were marker-free. This auto-excision system, mediated by the oxidative stress
      inducible FLP/FRT system to eliminate a selectable marker gene can be very
      readily adopted and used to efficiently generate marker-free transgenic plants.

PMID- 19160067
TI  - Quantitative evaluation of collateral circulation in patients with previous
      myocardial infarction: relation to myocardial ischemia, angiographic appearance
      and functional improvement of myocardium.
AB  - Evaluation of coronary pressures during angioplasty may functionally quantify
      collateral circulation. The aim of the study was to evaluate the relation between
      the amount of collateral circulation and development of myocardial ischemia
      during balloon occlusion, anatomic degree of collaterals, and functional
      improvement of myocardium. Study population consisted of 31 pts (mean age 53 +/-
      7 years; 25 male) with previous myocardial infarction and significant one-vessel
      stenosis undergoing angioplasty. Collateral circulation was calculated as the
      ratio between distal coronary pressure during balloon occlusion (P(w)) and aortic
      pressure (P(a)). Angiographic appearance of collaterals was evaluated by Rentrop
      classification. Patients were evaluated by echo for functional improvement of
      myocardium in the follow-up period. Mean P(w)/P(a) was 0.24 +/- 0.10 (range of
      0.07-0.51). Rentrop grade 0 of collaterals was present in 16 patients (52%),
      grade 1 in11 patients (35%), and grade 2 in 4 patients (13%). A mild correlation
      between angio and hemodynamic evaluation of collaterals was observed (r = 0.38, P
      = 0.035). In patients without ECG changes during angioplasty (21 pts, 68%),
      P(w)/P(a) was significantly higher in comparison to patients with ECG changes
      (0.28 +/- 0.09 vs. 0.15 +/- 0.06, P < 0.001; area under the curve 0.93). In
      patients with myocardial functional improvement during follow-up (21 pts, 68%),
      P(w)/P(a) was significantly higher than in the patients without echo improvement
      (0.26 +/- 0.10 vs. 0.18 +/- 0.08, P = 0.035). The amount of recruitable
      collaterals is not negligible even in the patients with no angio visible
      collaterals. Low values of P(w)/P(a) are associated with ECG changes during
      balloon occlusion. Higher P(w)/P(a) was associated with better functional
      improvement of myocardium.

PMID- 19160068
TI  - CT angiography; no collateral damage.

PMID- 19160069
TI  - Molecular cloning and characterization of a novel gene encoding zinc finger
      protein from Medicago sativa L.
AB  - A suppression subtraction hybridization (SSH) cDNA library had been constructed
      to identify differentially expressed genes. Based on the sequence of an expressed
      sequence tag (EST) homologous to Pisum sativum zinc finger protein mRNA
      (Accession number: AF160911), the full-length cDNA of 1,676 nucleotides was
      cloned from alfalfa by rapid amplification of cDNA ends (RACE). It was designated
      as MsZFN, encoding a protein of 418 amino acids. The amino acid sequence compared
      by blast revealed high homology with zinc finger protein of other plants.
      Sequence comparison showed that there were five conserved typical zinc finger
      motifs, and one sugar transfer protein signature. The calculated molecular weight
      of the MsZFN protein was 45.8 k Da, and theoretical isoelectric point was 8.13.
      The MsZFN localized in nucleus. Under normal growth conditions, differential
      expression of MsZFN exhibited that the expression was the highest in leaf and the
      lowest in root. MsZFN was quickly and transiently induced by NaCl treatment and
      reached its maximum at 30 min.

PMID- 19160070
TI  - Fluorometric probing on the binding of hematoxylin to serum albumin.
AB  - The binding of a cell nucleus stain, hematoxylin (HTL), to bovine serum albumin
      (BSA) was studied by spectroscopy including fluorescence spectra, UV-Visible
      absorption, circular dichroism (CD) spectra, synchronous and three-dimensional
      fluorescence spectra. The results indicated that the binding had led to static
      fluorescence quenching, with non-radiation energy transfer happening within
      single molecule. The observed binding constant was calculated to be 10(5.588) l
      mol(-1) at 311 K and one binding site had formed. The thermodynamic parameters of
      the interaction complied with DeltaG (theta) < 0, DeltaH (theta) < 0, DeltaS
      (theta) < 0 and the results indicate that hydrogen bonds played major role in the
      reaction. The distance r between donor (BSA) and acceptor (HTL) was obtained
      according to the Forster theory of non-radiation energy transfer. The structural
      change of BSA molecules with addition of HTL was analyzed and the optimized
      geometry of HTL-BSA was investigated by fluorescence probe method.

PMID- 19160071
TI  - Production of oligosaccharide from alginate using Pseudoalteromonas agarovorans.
AB  - A marine bacterium was isolated from seawater near the Korean south coast for
      efficient saccharification from alginate. Based on 16S rDNA sequence, the
      isolated strain was identified as Pseudoalteromonas agarovorans. Various
      environmental factors affecting saccharification of alginate using P. agarovorans
      CHO-12 have been investigated in flask cultures. The optimum concentration of
      sugar was obtained at 30 rpm and 29 degrees C. Among various NaCl concentrations,
      when NaCl concentration was increased from 10 to 30 g/l, the cell concentration
      sharply increased, while there is no increase at above 40 g/l. The maximum sugar
      concentration was obtained at 13.8 when 30 g/l of NaCl was used. Yeast extract
      and corn steep liquor were the best nitrogen source for efficient
      saccharification. Especially, the sugar concentration of 14.9 g/l was obtained
      after 3 days of culture using a mixture of 1.0 g/l of yeast extract and 1.5 g/l
      of corn steep liquor. Scale up was carried out at 50 l of reactor for 3 days
      using P. agarovorans CHO-12 and Stenotrophomonas maltophilia sp. When S.
      maltophilia was used, cell concentration was about twofold higher than that of P.
      agarovorans CHO-12. On the other hand, when P. agarovorans CHO-12 was used, the
      maximum saccharification rate was obtained, 7.5 g/l/day after 2 days of culture,
      which was about tenfold higher than that of S. maltophilia.

PMID- 19160072
TI  - Varied immune response to FVIII: presence of proteolytic antibodies directed to
      factor VIII in different human pathologies.
AB  - The versatility of antibodies is demonstrated by the various functions that they
      mediate such as neutralization, agglutination, fixation of the complement and its
      activation, and activation of effector cells. In addition to this plethora of
      functions, antibodies are capable of expressing enzymatic activity. Antibodies
      with catalytic function are a result of the productive interplay between the
      highly evolved machinery of the immune system and the chemical framework used to
      induce them (antigens). Catalytic antibodies are immunoglobulins with an ability
      to catalyze the reactions involving the antigen for which they are specific.
      Catalytic immunoglobulins of the IgM and IgG isotypes have been detected in the
      serum of healthy donors. In addition, catalytic immunoglobulins of the IgA
      isotype have been detected in the milk of healthy mothers. Conversely, antigen
      specific hydrolytic antibodies have been reported in a number of inflammatory,
      autoimmune, and neoplastic disorders. The pathophysiological occurrence and
      relevance of catalytic antibodies remains a debated issue. Through the
      description of the hydrolysis of coagulation factor VIII as model target antigen,
      we propose that catalytic antibodies directed to the coagulation factor VIII may
      play a beneficial or a deleterious role depending on the immuno-inflammatory
      condition under which they occur.

PMID- 19160073
TI  - The Ca(2+)-dependent activator protein for secretion CAPS: do I dock or do I
      prime?
AB  - The "Ca(2+)-dependent activator protein for secretion" (CAPS) is a protein which
      reconstitutes regulated secretion in permeabilized neuroendocrine cells. It is
      generally accepted that CAPS plays an important role in the release of the
      contents of dense core vesicles in the nervous system as well as in a variety of
      other secretory tissues. At which step in the exocytotic process CAPS functions
      as well as its role in the fusion of synaptic vesicles is still under dispute. A
      recent growth spurt in the CAPS field has been fueled by genetic approaches in
      Caenorhabditis elegans and Drosophila as well as the application of knockout and
      knockdown approaches in mouse cells and in cell lines, respectively. We have
      attempted to review the body of work that established CAPS as an important
      regulator of secretion and to describe new information that has furthered our
      understanding of how CAPS may function. We discuss the conclusions, point out
      areas where controversy remains, and suggest directions for future experiments.

PMID- 19160074
TI  - The novel compound heterozygous mutations, V434del and W666X, in WFS1 gene
      causing the Wolfram syndrome in a Chinese family.
AB  - Wolfram syndrome (WFS), also known as DIDMOAD, is an infrequent cause of diabetes
      mellitus. WFS is an autosomal recessive neurodegenerative disease characterized
      by various clinical manifestations such as diabetes mellitus, optic atrophy,
      diabetes insipidus, deafness, neurological symptoms, renal tract abnormalities,
      psychiatric disorders, and gonadal disorders. The majority of patients with WFS
      carry the loss of function mutations in the WFS1 gene. The exons 2-8 of the WFS1
      gene from one Chinese WFS patient were amplified by the polymerase chain reaction
      (PCR), subcloning techniques and direct sequence determination was applied to the
      amplified fragments. The compound heterozygous mutation of a 3-bp (GAC) deletion
      (V434del) and another compound heterozygous mutation (G-->N)(W666X) in exon 8 of
      WFS1 gene was identified in the patient. Other seventeen members of her family
      were investigated. Four cases with heterozygotes had been found through screening
      for the mutation V434del and five cases for the mutation W666X in the whole
      family. This is the first report of WFS with the mutation V434del and W666X in
      the WFS1 gene.

PMID- 19160075
TI  - Novel strategies to construct complex synthetic vectors to produce DNA molecular
      weight standards.
AB  - DNA molecular weight standards (DNA markers, nucleic acid ladders) are commonly
      used in molecular biology laboratories as references to estimate the size of
      various DNA samples in electrophoresis process. One method of DNA marker
      production is digestion of synthetic vectors harboring multiple DNA fragments of
      known sizes by restriction enzymes. In this article, we described three novel
      strategies-sequential DNA fragment ligation, screening of ligation products by
      polymerase chain reaction (PCR) with end primers, and "small fragment
      accumulation"-for constructing complex synthetic vectors and minimizing the mass
      differences between DNA fragments produced from restrictive digestion of
      synthetic vectors. The strategy could be applied to construct various complex
      synthetic vectors to produce any type of low-range DNA markers, usually available
      commercially. In addition, the strategy is useful for single-step ligation of
      multiple DNA fragments for construction of complex synthetic vectors and other
      applications in molecular biology field.

PMID- 19160076
TI  - A new positive/negative selection scheme for precise BAC recombineering.
AB  - Recombineering technology allows the modification of large DNA constructs without
      using restriction enzymes, enabling the use of bacterial artificial chromosomes
      (BACs) in genetic engineering of animals and plants as well as in the studies of
      structures and functions of chromosomal elements in DNA replication and
      transcription. Here, we report a new selection scheme of BAC recombineering. A
      dual kanamycin and streptomycin selection marker was constructed using the
      kanamycin resistance gene and bacterial rpsL (+) gene. Recombination cassettes
      generated using this dual marker was used to make precise modifications in BAC
      constructs in a two-step procedure without leaving behind any unwanted sequences.
      The dual marker was first inserted into the site of modifications by positive
      selection of kanamycin resistance. In the second step, the counter-selection of
      streptomycin sensitivity resulted in the replacement of the dual marker with
      intended modified sequences. This method of BAC modification worked as
      efficiently as the previously reported galK method and provided a faster and more
      cost-effective alternative to the galK method.

PMID- 19160077
TI  - Lack of somatic mutations in VEGFR-2 tyrosine kinase domain in hepatocellular
      carcinoma.

PMID- 19160078
TI  - Rat model of reperfused partial liver infarction: characterization with
      multiparametric magnetic resonance imaging, microangiography, and
      histomorphology.
AB  - BACKGROUND: Rat model of reperfused partial liver infarction (RPLI) has been
      increasingly used in studying new diagnostics and therapeutics. PURPOSE: To
      characterize the RPLI model using magnetic resonance imaging (MRI),
      microangiography, and histopathology. MATERIAL AND METHODS: RPLI was induced in
      eight rats by occluding hepatic inflow to the right liver lobe for 3 hours. MRI
      was performed at a 1.5 T clinical scanner 6 hours after reperfusion to obtain T2
      weighted (T2WI), T1-weighted (T1WI), contrast-enhanced (CE) T1WI, diffusion
      weighted imaging (DWI) with apparent diffusion coefficient (ADC) maps, T1
      weighted dynamic contrast-enhanced (T1-DC) perfusion-weighted imaging (PWI), and
      T2*-weighted dynamic susceptibility contrast-enhanced (T2*-DSC) PWI images. Rats
      were sacrificed for microangiography and histomorphology. In vivo morphological
      and functional MRI parameters, including maximum initial slope (MIS), K value,
      relative blood flow (rBF), relative blood volume (rBV), time to peak (TTP), and
      mean transit time (MTT), were matched with postmortem findings. RESULTS: The
      infarcted lobe was conspicuous from normal liver with lower and higher signal
      intensity on T1WI (P=0.018) and T2WI (P=0.001), respectively. Contrast between
      infarcted and normal liver reversed on CE-T1WI after gadolinium injection. The
      infarction averaged 37.5% of total liver volume. DWI and ADC maps were able to
      detect subtle perfusion-related differences (P<0.05). With T1-DC-PWI, increased
      extravasation and vascular permeability were reflected by significantly greater
      MIS (P=0.034) and K value (P=0.014) in infarction. T2*-DSC-PWI showed lower rBF
      and rBV with shorter TTP and MTT in infarcted liver (P<0.05). In vivo MRI
      findings corresponded well with postmortem outcomes. CONCLUSION: RPLI in rats
      could be characterized by multiparametric MRI and postmortem assessments, with
      insight into the no-reflow phenomenon, which implies its further application for
      preclinical assessments of new pharmaceutics.

PMID- 19160079
TI  - Effects of gadolinium contrast agents in naive and nephrectomized rats: relevance
      to nephrogenic systemic fibrosis.
AB  - BACKGROUND: Human nephrogenic systemic fibrosis (NSF) is a rare condition
      reported in patients with severe renal insufficiency exposed to a gadolinium (Gd)
      based contrast agent. An animal model of NSF could help to investigate its
      mechanisms and lead to prevention and treatment. PURPOSE: To evaluate a possible
      animal model of NSF using naive and partially nephrectomized rats to induce
      conditions similar to those in patients at risk of NSF. MATERIAL AND METHODS:
      Naive rats received intravenous doses of 5 or 10 mmol/kg Omniscan; 5 mmol/kg
      Magnevist; 1 mmol/kg caldiamide; 1, 2.5, or 5 mmol/kg gadodiamide; 25 micromol/kg
      GdCl(3); or 25 micromol/kg Gd citrate. Partially nephrectomized rats received 5
      mmol/kg Omniscan; 5 mmol/kg Magnevist; 1 mmol/kg caldiamide; 1 mmol/kg
      gadodiamide; 25 micromol/kg GdCl(3); or 25 micromol/kg Gd citrate. There were
      three or four animals per group. Clinical signs were recorded during treatment.
      At termination, clinical biochemistry, histopathology, and tissue Gd and Zn
      concentrations were investigated. RESULTS: Similar responses to treatment were
      seen in naive and nephrectomized rats. High doses of gadodiamide were toxic,
      necessitating early termination of the affected animals. Skin lesions appeared in
      naive and nephrectomized groups treated with gadodiamide or Omniscan, coinciding
      with the onset of signs of pruritus, i.e., intensive scratching. The
      histomorphological features of the skin lesions were also consistent with
      superficial physical trauma. Dermal fibrosis was not a feature of these skin
      lesions in any of the groups, i.e., no increased collagen density, CD34+ cells,
      or increased fibroblasts. This was supported by skinfold measurements that
      demonstrated no increased skin thickness. Treatment with the gadolinium-based
      contrast agents and Gd salts resulted in increased Gd content of several tissues.
      The Gd salts were mainly taken up by the liver and spleen, possibly reflecting
      formation of insoluble particles and macrophage uptake. Zn tissue concentrations
      were normal or increased. Other major treatment-related changes included
      increased serum rat C-reactive protein and histamine; mineralization affecting
      the dermis, stomach, and blood vessels; and renal proximal tubule vacuolation.
      CONCLUSION: The visible skin lesions seen in this study appeared to be caused by
      excessive scratching in response to pruritus. As there was no evidence of dermal
      fibrosis, the cardinal feature of human NSF, this did not appear to be a model of
      human NSF.

PMID- 19160080
TI  - Percutaneous retrieval of dislodged central venous port catheter: experience of
      25 patients in a single institute.
AB  - BACKGROUND: For a dislodged port catheter, percutaneous retrieval by using a loop
      snare or a basket is the standard technique, with high success. However, once a
      loop snare fails, the likelihood of success with other tools is considered low.
      PURPOSE: To report our experience of percutaneous retrieval of dislodged port
      catheters and to emphasize the usefulness of grasping forceps. MATERIAL AND
      METHODS: During a 6-year period, a total of 25 dislodged port catheters were
      retrieved in our institute. The interval between port catheter implantation and
      dislodged catheter retrieval was 3-85 months (mean 23 months). The time of
      delayed retrieval ranged from 3 to 604 days (mean 58 days). A loop snare or
      grasping forceps were used via either the femoral or jugular route. RESULTS: The
      prevalence of port catheter dislodgement was 0.4% in our institute. All dislodged
      port catheters were successfully removed, including four patients with delayed
      retrieval of more than 90 days. A loop snare was used in 20 patients, with
      technical success in 18. Grasping forceps were used in seven patients, all with
      success (including the two patients who failed by initial use of a loop snare).
      No procedure-related complications were encountered, except transient arrhythmia
      in four patients requiring no medication. CONCLUSION: Although the prevalence of
      port catheter dislodgement is low, percutaneous attempts at retrieval should be
      performed in all patients, even in chronic settings. A loop snare is the
      instrument of choice for retrieval. Grasping forceps can be used as an auxiliary
      instrument, especially in patients where a loop snare fails.

PMID- 19160081
TI  - Transcatheter coil embolization for steal syndrome in patients with hemodialysis
      access.
AB  - BACKGROUND: Drainage of large amounts of shunt blood into deep veins via
      collaterals reduces resistance to venous outflow and decreases blood flow to the
      artery distal to the arterial anastomotic site, potentially resulting in steal
      syndrome. PURPOSE: To evaluate the effectiveness of transcatheter coil
      embolization for collateral veins of hemodialysis access in the treatment of
      steal syndrome. MATERIALS AND METHODS: Five hemodialysis patients (four male, one
      female; mean age 58.8 years, range 40-71 years) with symptomatic steal syndrome
      were treated. Steal syndrome was diagnosed based on decreased or absent distal
      pulse, coolness, pain, abnormal skin color, ischemic ulceration of digits,
      numbness, sensory impairment, or motor impairment. Coil embolization was
      performed to block collaterals communicating with deep veins, with conscious
      sedation and local anesthesia. Fistulography was performed before, immediately
      after, and 1 month after embolization. Ultrasonography was performed 2 days after
      embolization. Symptoms and signs were assessed 2 days after embolization.
      Clinical findings related to steal syndrome and access failure were observed at
      each hemodialysis. RESULTS: Blood flow in the collaterals was successfully
      blocked by coil embolization in all patients. Distal pulse, coolness, pain, and
      skin color improved in all patients. Numbness, sensory impairment, and motor
      impairment were unimproved in two patients. In all patients, hemodialysis
      following embolization was performed normally. The mean observation period after
      embolization was 33 months (range 9-75 months). CONCLUSION: Coil embolization of
      collaterals that drain shunt blood into deep veins is effective for steal
      syndrome for hemodialysis access originating in the brachial artery.

PMID- 19160082
TI  - Expansion of radiofrequency ablation volume by saturated NaCl saline injection in
      the area of vaporization.
AB  - BACKGROUND: Vaporization around the radiofrequency (RF) electrode after RF
      application (RFA) limits the RF ablation area. PURPOSE: To determine whether
      saturated saline injected into the area of vaporization after initial RFA extends
      ablation area after further RFA. MATERIAL AND METHODS: RFA was performed in 18 ex
      vivo porcine livers and four in vivo rabbit erector spinae muscles. An RF
      electrode was used to ablate an area with 40W of parallel current for 15 min. The
      ablation margin was determined using a thermocouple, and the radius of the
      ablated area was measured. After RF electrode removal, saturated saline was
      infused through a percutaneous ethanol injection needle into the site of the
      original RFA in 11 liver samples and two erector spinae muscles. Three minutes
      later, RFA was resumed for 15 min. The remaining seven control liver samples and
      two spinae muscles received RFA without saline injection. The radius of the final
      ablated area was then measured. RESULTS: In the ex vivo study, injection of
      saturated saline significantly decreased tissue impedance (87.7+/-9.4 to 51.1+/
      9.7 Omega, P<0.0001), and increased the mean radius of the ablated area (15.9+/
      3.0 to 25.0+/-3.6 mm, P<0.0001). These significant changes were not observed
      without injection of saturated saline. Similar trends were found in the in vivo
      study. CONCLUSION: Injection of saturated saline into the area of vaporization
      around the RF electrode, followed by additional RFA, caused concentric expansion
      of the final ablation area, facilitating more efficient tumor ablation.

PMID- 19160083
TI  - Enhanced host immune recognition of mastitis causing Escherchia coli in CD-14
      transgenic mice.
AB  - Escherchia coli causes mastitis, an economically significant disease in dairy
      animals. E. coli endotoxin (lipopolysaccharide, LPS) when bound by host membrane
      proteins such as CD-14, causes release of proinflammatory cytokines recruiting
      neutrophils as an early, innate immune response. Excessive proinflammatory
      cytokines causes tissue damage, compromising mammary function. If present,
      soluble CD-14 (sCD-14) might out compete membrane bound CD-14, lessening the
      severity of the inflammatory response. To test this hypothesis transgenic mice,
      expressing sCD-14 in their milk (31 to 316 microg/ml), were evaluated. A cell
      culture study demonstrated, in the presence of LPS, milk from transgenic mice
      increased secretion of cytokine IL-8 compared to milk from nontransgenic
      littermates (18 +/- 3 vs. 35 +/- 2 ng/mL, p < 0.001). To assess protection
      afforded by the transgene, glands were infused with E. coli. Recovery of bacteria
      showed no clear relationship between sCD14 concentration and the number of
      organisms recovered; however, there was a strong relationship between sCD14
      concentration and edema (r(2) = 0.999, p < 0.001), as measured by weight of fluid
      in harvested glands. Highest expressing lines had the least edema, suggesting the
      presence of sCD14 had an effect on reducing the inflammatory response to E. coli,
      thus, possibly protecting against gland tissue damage.

PMID- 19160084
TI  - Targeted nucleotide exchange in bovine myostatin gene.
AB  - The myostatin gene, known as Growth Differentiation Factor 8 (GDF8), located at
      chromosome 2 (BTA2) in cattle, is specifically expressed during embryo
      development and in the adult skeletal muscle. Molecular analysis of this gene
      reveals the presence of three exons and two introns. Several cattle breeds, such
      as Piedmontese, Belgian Blue, Blond'Aquitaine, among others, show polymorphisms
      in this gene, which are directly related to double muscling phenotype.
      Piedmontese cattle shows a nucleotide transition G --> A (G938A) at exon 3,
      resulting in the substitution of cysteine to tyrosine, leading to a protein
      structure change, which determines myostatin inactivation and consequent muscular
      hypertrophy. The objective of this work was to implant the polymorphism G938A,
      naturally existent in Piedmontese breed, into in vitro propagated foetal
      myoblasts, from Nellore cattle. Single strand DNA (ssDNA) oligonucleotides were
      used to direct the same nucleotidic transition (G938A) to exon 3. Two
      transfection protocols (cationic lipid solution and electroporation) were tested
      and, 48 hours after transfection, RNA and DNA were extracted from myoblasts.
      Reverse transcription and polymerase chain reaction (PCR) were performed, using
      primers flanking the mutation region. The PCR products were cloned and analyzed
      by DNA sequencing, and it was possible to detect the nucleotidic CT transition at
      position 938, in the electroporated myoblasts. The existence of a positive signal
      in the transfection indicates that ssDNA oligonucleotides can be used to
      introduce this point mutation in specific functional gene sites.

PMID- 19160085
TI  - Genomic location of the bovine growth hormone secretagogue receptor (GHSR) gene
      and investigation of genetic polymorphism.
AB  - The growth hormone secretagogue receptor (GHSR) is involved in the regulation of
      energetic homeostasis and GH secretion. In this study, the bovine GHSR gene was
      mapped to BTA1 between BL26 and BMS4004. Two different bovine GHSR CDS (GHSR1a
      and GHSR1b) were sequenced. Six polymorphisms (five SNPs and one 3-bp indel) were
      also identified, three of them leading to amino acid variations L24V, D194N, and
      Del R242. These variations are located in the extracellular N-terminal end, the
      exoloop 2, and the cytoloop 3 of the receptor, respectively.

PMID- 19160086
TI  - Porcine type III RNA polymerase III promoters for short hairpin RNA expression.
AB  - Based on the highly conserved sequences of small nuclear RNA and small
      cytoplasmic RNA between vertebrate species, three porcine type III RNA polymerase
      III promoters, pY1, pY3 and pU6, were identified by using genomic DNA walking. To
      test the functional relationship of these sequences, the human H1 promoter of
      pSUPER-EGFP-l-neo vector was substituted with these three promoters to create the
      ppPol III-MCS vectors. The strength of each promoter was measured by its ability
      to derive expression of shRNA to repress expression of luciferase via RNA
      interference in the pig kidney epithelial cell line LLC-PK1. We determine that
      the ranking of promoter strength in descending order is pU6 > pY1 > pY3.

PMID- 19160087
TI  - Molecular cloning and expression analysis of CD127 in pig.
AB  - CD127 (the alpha chain of the IL-7 receptor) is an 80 kDa type I membrane
      glycoprotein that mediates the signal for the differentiation, maturation, and
      survival of lymphocyte development. In this study, the full-length cDNA of pig
      Cd127 was cloned and sequenced. Pig CD127 cDNA contains an open reading frame
      (1,380 bp) encoding 459 amino acids. Phylogenetic analysis revealed that pig
      CD127 is most homologous to that of cow (Bos taurus) with 87% amino acid identity
      and less homologous to that of chicken (Gallus gallus) with 36% amino acid
      identity among those of species. Structurally, pig CD127 has well-conserved
      cytoplasmic tail that transmits a signal and little diversity of extracellular
      domain, compared with those of other mammalian species. Expression analysis
      indicates that the mRNA transcript of pig CD127 is mainly detected in lymphoid
      tissues, but still detected in nonlymphoid tissues. Future studies will be
      focused on determining a more defined expression pattern of pig CD127 and the
      role of CD127 during the lymphocyte development in pigs.

PMID- 19160089
TI  - A system for quantitative evaluation of fixatives for light microscopy using
      paraffin sections of kidney and brain.
AB  - A numerical scoring system is presented for evaluating structural fixation of
      certain mammalian tissues for light microscopy. Small pieces of rat's kidney and
      brain, tissues for which artifacts of fixation are well documented, were fixed in
      various fluids. Random code numbers hid their identities, and paraffin sections
      were stained to show nuclear chromatin, cytoplasm and extracellular materials.
      Two sections of each specimen were examined and awarded scores according to
      described schemes, for microanatomical and cytological fixation. The assessment
      was confined to preservation of structure; chemical changes were not taken into
      account. When the code was broken, the scores for both sections of each specimen
      from each fixative were added. The scores obtained (24 best to eight worst) are
      generally comparable to the grades (I-V) given for traditional fixatives by JR
      Baker. The criteria for quality of fixation were defined more explicitly than
      those for Baker's grading method, which used mouse testis as the test object.
      Assessments are presented for several traditional fixatives and for four zinc
      formaldehyde mixtures. The scoring system should be useful for evaluating newly
      developed fixatives for animal tissues for light microscopic examination of
      paraffin sections. In an evaluation of four traditional fixatives and four zinc
      formaldehyde mixtures, variation among three different observers was only +/-1
      point on either side of the median score for microanatomical or cytological
      preservation by any of the eight fixatives. This approach has certain
      limitations, notably that the criteria for cytological fixation do not include
      the preservation of chromosomes or specific cytoplasmic organelles.

PMID- 19160088
TI  - High prevalence of four long QT syndrome founder mutations in the Finnish
      population.
AB  - AIMS: Long QT syndrome (LQTS) is an inherited arrhythmia disorder with an
      estimated prevalence of 0.01%-0.05%. In Finland, four founder mutations
      constitute up to 70% of the known genetic spectrum of LQTS. In the present
      survey, we sought to estimate the actual prevalence of the founder mutations and
      to determine their effect sizes in the general Finnish population. METHODS AND
      RESULTS: We genotyped 6334 subjects aged > or =30 years from a population cohort
      (Health 2000 study) for the four Finnish founder mutations using Sequenom MALDI
      TOF mass spectrometry. The electrocardiogram (ECG) parameters were measured from
      digital 12-lead ECGs, and QT intervals were adjusted for age, sex, and heart rate
      using linear regression. A total of 27 individuals carried one of the founder
      mutations resulting in their collective prevalence estimate of 0.4% (95% CI 0.3%
      0.6%). The KCNQ1 G589D mutation (n=8) was associated with a 50 ms (SE 7.0)
      prolongation of the adjusted QT interval (P=9.0x10(-13)). The KCNH2 R176W variant
      (n=16) resulted in a 22 ms (SE 4.7) longer adjusted QT interval (P=2.1x10(-6)).
      CONCLUSION: In Finland 1 individual out of 250 carries a LQTS founder mutation,
      which is the highest documented prevalence of LQTS mutations that lead to a
      marked QT prolongation.

PMID- 19160090
TI  - R.W. Mowry.

PMID- 19160091
TI  - Methylation patterns of Rb1 and Casp-8 promoters and their impact on their
      expression in bladder cancer.
AB  - Aberrant methylation of the promoter CpG island of human genes is an alternative
      gene inactivation mechanisms that contributes to the carcinogenesis of human
      tumors. We tried to determine the methylation status and its impact on the
      expression of two tumor related genes Casp-8 and Rb1 in 103 bladder tumor tissues
      and 48 control paraffin-embedded tissues by using MSP-PCR and SQRT-PCR. Of the
      patients, 19.4% for Casp-8 and 28.2% for Rb1 showed methylation in bladder
      cancer. There were significant differences between patients and healthy controls
      in methylation of Rb1 (p = 0.001) and Casp-8 (p = 0.008) and especially when both
      genes methylated (p = 0.004). Methylation of Casp-8 has mostly been taken places
      in patients with age >60 years (p = 0.013) whereas methylation of Rb1 has taken
      place in age >60 (p = 0.018) as well as in patients age <60 (p = 0.027). Patients
      with methylated of both genes with stage T2 showed an increasing risk of 4.75
      fold (95% CI = 2.87-7.85, p = 0.00) and for stage T3, 23.50 fold (95% CI = 6.05
      91.21, p = 0.00) of bladder cancer. Smoking showed a high significant effect on
      methylation (p = 0.00 in compare to non-smoker patients), especially in those
      with pack-years more than 44.7 (OR = 3.53, 95% CI = 1.69-7.35, p = 0.001). The
      risk of bladder cancer was marginally associated in drinker patients (OR = 1.78,
      95% CI = 1.42-2.24, p = 0.010) featuring both genes methylated, especially in
      those patients consumed alcohol units>30 per week (OR = 4.57, 95% CI = 2.38-8.80,
      p = 0.000). Significant reduction in expression has been detected in patients
      with methylated Rb1 (p = 0.00) and Casp-8 (p = 0.03). These results suggest that
      age, smoking and drinking will increase the probability of methylation of these
      genes and consequently increased risk of developing of bladder cancer to higher
      stages of disease. Interestingly, it has been deduced that methylation by itself
      maybe significantly have a role on reducing the expression ofRb1, but it seems
      that methylation along with risk factors lead to decrease the expression of Casp
      8. Methylation of Rb1 can be considered as one of prognosis indicator for
      progression and development bladder cancer.

PMID- 19160092
TI  - p53 Mutations in carcinoma of the esophagus and gastroesophageal junction.
AB  - BACKGROUND: Recent studies suggested p53 mutations as a prognostic factor. Tumors
      of the esophagus and gastroesophageal (GE) junction show raising incidence with a
      general poor prognosis. METHODS: p53 Mutational spectra in 103 patients (68
      squamous cell carcinoma/SCC and 35 adenocarcinoma/AC) were compared to clinical
      and pathologic data. RESULTS AND CONCLUSIONS: p53 Mutations were found in 26 of
      68 SSC (38.2%) and in 12 of 35 AC (34.5%). We only found G > T transversions in
      smokers with SCC. The survival of patients was not affected by p53 mutational
      status. In our study, the frequency and mutational spectrum of mutant p53 is
      similar in both histological types without prognostic relevance.

PMID- 19160093
TI  - Low expression of Foxo3a is associated with poor prognosis in ovarian cancer
      patients.
AB  - To investigate whether Foxo3a expression is correlated with p27(kip1) protein
      levels as well as how it might be clinically relevant, we evaluated the
      expression of Foxo3a in several ovarian tumors. Immunohistochemical analysis was
      performed in 63 cases of ovarian tumors. Ten cases were evaluated by Western blot
      analysis. There was a correlation observed between Foxo3a over-expression and
      clinic pathological parameters (p = 0.032). Kaplan-Meier survival analysis showed
      that Foxo3a low expression was significantly associated with poor prognosis of
      patients. It may be a useful prognostic marker and target in ovarian cancer.

PMID- 19160094
TI  - The myth of measurable disease in ovarian cancer: revisited.
AB  - There are well-documented and serious limitations associated with analyzing
      measurable disease in ovarian cancer as a sole primary endpoint in clinical
      trials, as this focus requires the presence of individual tumor masses of
      sufficient size and distinctive shape to image. An alternative highly rational
      strategy adds the routine monitoring of validated serum tumor markers (e.g., CA
      125), which can more adequately define changes in "tumor volume" associated with
      small nonvisualized macroscopic and diffuse microscopic cancer.

PMID- 19160095
TI  - EB1089 induces Skp2-dependent p27 accumulation, leading to cell growth inhibition
      and cell cycle G1 phase arrest in human hepatoma cells.
AB  - EB1089 exhibits a high level of antiproliferative activity against various
      tumors. However, it is not known whether the mechanism of EB1089 induced the
      growth inhibition in human hepatic-carcinoma. Here we found that EB1089
      significantly reduced cell growth in human hepatoma cells (Hep-G2) and blocked
      Hep-G2 cell-associated tumor formation in nude mice. The growth inhibition was
      linked to cell cycle G1 phase arrest by the accumulation of p27 and a reduction
      of Skp2. Knockdown of Skp2 reversed the p27 induction and G1 arrest. Taken
      together, our data indicate that EB1089 inhibitory activity is associated with
      alteration of cell cycle checkpoints through Skp2-dependent p27 induction in Hep
      G2 cells.

PMID- 19160096
TI  - Analysis of hMSH2 mismatch repair protein expression in dysplasia, carcinoma in
      situ and invasive squamous cell carcinoma of the vocal folds.
AB  - The expression pattern of hMSH2 mismatch repair protein during the progression of
      benign epithelium to vocal fold invasive squamous cell carcinoma has not been
      previously described. Nor has the correlation between the hMSH2 protein
      expression and the clinicopathologic features of the vocal fold dysplasia and
      carcinoma been examined. HYPOTHESIS: "The progression of benign epithelium to
      invasive squamous cell carcinoma of the vocal folds is associated with reduction
      of the hMSH2 mismatch repair protein expression." METHODS: Vocal fold biopsies
      were obtained from 20 patients with mild and moderate dysplasia: 10 patients with
      severe dysplasia (squamous cell carcinoma in situ) and 20 patients with invasive
      squamous cell carcinoma. The expression pattern of hMSH2 protein was examined by
      using immunoperoxidase-staining methods and mouse monoclonal antibodies. The
      results were scored as the percentage of hMSH2 positively stained cells. RESULTS:
      The mean values of hMSH2 positively stained cells decreased gradually with the
      transitions from normal epithelium to dysplasia and finally to invasive squamous
      cell carcinoma. There was a negative correlation between the expression of hMSH2
      and the degree of dysplasia, that is, as the severity of the dysplasia increases
      at the microscopic level, there was a decrease in the expression values of the
      hMSH2 protein. CONCLUSIONS: We report, for the first time, that the reduced
      expression of the hMSH2 mismatch repair protein is related to the progression of
      the benign epithelium to invasive squamous cell carcinoma of the vocal folds.

PMID- 19160097
TI  - NS-398 induces apoptosis in human esophageal cancer cells through inhibition of
      NF-kappaB downstream regulation of cyclooxygenase-2.
AB  - Although non-steroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to
      have cancer-preventive effects and induce apoptosis of cancer cells, the
      mechanism of their effects is not clearly known. We studied the mechanism in
      human esophageal cancer cell line TE13. The esophageal squamous cell carcinoma
      cell line TE-13 was cultured with NS-398 at different concentrations or for
      different times. Proliferation and apoptosis were measured by MTT reduction and
      flow cytometry. Prostaglandin F(1alpha) was determined with radioimmunoassay.
      Expression of COX-2 mRNA was measured by RT-PCR and COX-2 protein levels with
      Western blot analysis. Nuclear NF-kappaB and cytoplasmic IkappaB protein levels
      were determined by electrophoretic mobility shift assay and Western blot,
      respectively. NS-398 significantly inhibited cell proliferation and induced
      apoptosis at concentrations of 0.001, 0.01, 1, and 100 micromol/L. NS-398 dose
      dependently decreased the levels of COX-2 mRNA, COX-2 protein, nuclear NF-kappaB
      protein and production of PGF(1alpha) and increased the cytoplasmic IkappaB
      protein. In conclusion, NS-398 inhibits the proliferation of, and induced
      apoptosis in, the cultured TE-13 SCC cell line. These changes correlate with a
      reduction in COX-2 mRNA and protein expression, prostaglandin synthesis, an
      inhibition of NF-kappaB nuclear translocation, and an increase in cytoplasmic
      IkappaB.

PMID- 19160098
TI  - The incidence and risk of venous thromboembolism associated with cancer and
      nonsurgical cancer treatment.
AB  - Patients with cancer are at high risk of developing venous thromboembolism, a
      risk that varies according to the type of malignancy and its disease stage, and
      is steadily increased by concomitant patient-related thrombotic risk factors,
      such as advanced age, infection, heart disease, respiratory disease, as well as
      hospitalization, surgical, and nonsurgical cancer treatments. Current evidence
      based guidelines raise awareness of the importance of thromboprophylaxis in
      hospitalized cancer patients and highlight the thrombotic risks of combined
      chemotherapy regimens. Therefore, they recommend that all patients hospitalized
      or bedridden owing to cancer should be considered for thromboprophylaxis in the
      absence of contraindications to anticoagulant therapy.

PMID- 19160099
TI  - Aberrant CpG island hypermethylation of RASSF1A in gastric cardia adenocarcinoma.
AB  - Ras-association domain family 1A (RASSF1A) gene, a candidate tumor suppressor
      gene, is inactivated in several human tumors, usually by hypermethylation of its
      promoter region. RASSF1A induces cell cycle arrest through inhibition of cyclin
      D1 accumulation. In this work, the promoter methylation status of the RASSF1A in
      92 gastric cardia adenocarcinoma (GCA) and corresponding normal tissues were
      investigated using Methylation-specific PCR (MSP) approach, immunohistochemistry
      method and RT-PCR were used respectively to examine the protein expression and
      mRNA expression of RASSF1A in tumors and corresponding normal tissues. Cyclin D1
      expression was examined by immunohistochemistry. RASSF1A was methylated in 54/92
      (58.7%) tumor specimens, which was significantly higher than that in
      corresponding normal tissues (p <.001). Methylation frequencies of stage III and
      IV tumor tissues were significantly higher than that in stage I and II tumor
      tissues (p <.05). By immunostaining, 43/92 (46.7%) tumor tissues demonstrated
      heterogeneous, positive immunostaining of tumor tissues was significantly reduced
      with comparison to matched normal tissues (p <.001). mRNA expressions of RASSF1A
      in GCA tumor tissues were reduced significantly with comparison to the
      corresponding normal tissues (OD value: 0.2376 +/- 0.2315 vs 0.6874 +/- 0.2668, p
      <.001). RASSF1A mRNA expression in methylation group of GCA was significantly
      different from that in unmethylation group (p <.001). Cyclin D1 hyper-expression
      was found in 72/92 (78.3%) cases and correlated with RASSF1A methylation (p
      <.05). Our data suggested that epigenetic silencing of RASSF1A gene expression by
      promoter hypermethylation may play an important role in GCA.

PMID- 19160100
TI  - CD147 impacts angiogenesis and metastasis formation.
AB  - CD147 is highly expressed on many tumor cells; its role for tumor invasiveness
      and metastasis has been deduced from its capacity to induce MMPs, i.e., MMP-1, 
      2, -3, and -9. However, in the murine B16 melanoma model, MMP-2/-9 expression
      occurs independent of CD147. To scrutinize the impact of CD147 on metastasis
      formation and angiogenesis in this model, CD147 was stably knocked down in B16
      cells. This silencing of CD147 expression resulted in a reduced capability of the
      tumor cells to metastasize to the draining lymph nodes. Notably, the CD147 knock
      down caused a decreased VEGF expression in vivo accompanied by reduced blood
      vessel formation. Thus, in the B16 melanoma model, CD147 promotes metastasis
      formation by induction of angiogenesis in an MMP independent manner.

PMID- 19160101
TI  - CYP1A1 and GSTM1 polymorphisms and oral cancer risk: association studies via
      evidence-based meta-analyses.
AB  - Previous studies have implicated CYP1A1 and GSTM1 polymorphisms as risk factors
      for various cancers. A number of studies have been devoted to the association of
      CYP1A1 or GSTM1 polymorphism with susceptibility to oral carcinoma and have
      yielded conflicting results. The aim of the present study was to assess the
      possible associations of oral cancer risk with CYP1A1 genetic variation and GSTM1
      null genotype respectively via systematic meta-analyses. The data suggest that
      variant genotypes of CYP1A1 might not be risk factors for oral cancer, whereas
      GSTM1 null genotype significantly increases susceptibility to oral cancer in
      Asians but not Caucasians.

PMID- 19160102
TI  - Phosphorylation of telomeric repeat binding factor 1 (TRF1) by Akt causes
      telomere shortening.
AB  - Telomeric repeat binding factor 1 (TRF1) belongs to the shelterin complex, which
      modulates the telomere structures. Akt/protein kinase B activation caused genomic
      instability and contributes to tumorigenesis, although the molecular mechanism
      remained little known. Here, we show the direct interaction between Akt and TRF1.
      In vitro kinase assays showed the phosphorylation of a putative Akt
      phosphorylation site (Threonine 273) in wild type TRF1, but not the mutant TRF1
      (T273A), by Akt. Overexpression of Akt decreased telomere length in a HTC cell
      line. These results indicate that Akt plays an important role in telomere length
      regulation, contributing to genomic instability and tumorigenesis.

PMID- 19160103
TI  - Sensitivity and specificity of oral brush biopsy.
AB  - The aim of this study was to evaluate the advantage of computer-assisted analysis
      of the oral brush biopsy compared with synchronous scalpel biopsy in the early
      detection of oral lesions. In this prospective, randomized, controlled study,
      brush and scalpel biopsies were performed on 75 patients. Six patients had to be
      excluded due to inadequate results, and 43 were shown to have dysplastic
      epithelium, 15 carcinoma, and 11 suspicious lesions. Therefore, the sensitivity
      for the detection of abnormal cells by means of OralCDx was 52%, specificity 29%,
      and the positive predictive value 63%. According to our results, the use of oral
      brush biopsy as a standardized, minimally invasive method of screening oral
      lesions should be reconsidered.

PMID- 19160104
TI  - Aspiration risk and postoperative radiation for head and neck cancer.
AB  - The aim of the study was to assess the aspiration risk following postoperative
      radiation for head and neck cancer. Thirty-seven patients had Modified Barium
      Swallow before and following treatment. Dysphagia severity was graded from 1 to
      7. Before treatment there were sixteen grade 1, seventeen grade 2, three grade 3
      and one grade 5. Following postoperative radiation, two patients had grade 1,
      eleven patients had grade 2, thirteen patients had grade 3, four patients had
      grade 4, four patients had grade 5, one patients had grade 6, and two patients
      had grade 7. Nineteen percent (7/37) of the patients developed aspiration (grade
      5-7). Aspiration is life-threatening and may develop for all tumor sites and
      stages.

PMID- 19160105
TI  - T lymphocyte subsets determination and DNA ploidy analysis in the differential
      diagnosis between benign and malignant ascites.
AB  - Differentiating malignant from benign ascites often leads to confusion and an
      inability to exclude its multitude of causes in many patients. In the present
      study, T lymphocyte subsets and DNA ploidy in ascitic fluid were detected by flow
      cytometer. There were significant differences in T lymphocyte subsets between
      benign and malignant ascites. For malignant ascites, the sensitivity of DNA
      aneuploid is 75.6%, the specificity is 79.0%, and the accuracy is 77.6%. The
      results demonstrate that T lymphocyte subsets determination and DNA ploidy
      analysis can be used in the differential diagnosis between benign and malignant
      ascites.

PMID- 19160106
TI  - Construction and characterization of a novel superantigen fusion protein:
      bFGF/SEB.
AB  - BACKGROUND: As one of the bacterial superantigens, Staphylococcal enterotoxins
      (SEs) are potent activators of T cells, especially for those expressing T cell
      receptor V(beta) chains, and can induce the production of cytokines such as IFN
      gamma, TNF-alpha, IL-1, IL-2, IL-6, IL-12, etc. Thus, SEs could be used in tumor
      targeting therapy when cooperated with the vectors that can specifically
      recognize the tumor cells. MATERIALS AND METHODS: The coding sequences of
      Staphylococcal enterotxin B (SEB) was amplified and fused with human basic
      fibroblast growth factor (bFGF). Recombinant protein SEB and fusion protein
      bFGF/SEB were expressed and purified. The biological activity was detected,
      including splenocytes proliferation, cytokine production, and cytotoxicity in
      tumor cells in vitro. In addition, the binding of bFGF/SEB with tumor cells and
      the tumor cell apoptosis were also tested by immunofluorescent technique.
      RESULTS: The fusion protein bFGF/SEB had similar biological activities compared
      with natural SEA and recombinant SEB, including tumor-inhibition ratio.
      CONCLUSION: The recombinant bFGF/SEB-fusion protein was shown to retain the
      superantigenic activity of SEB, and might be a novel promising immunotherapeutic
      agent for the treatment of some carcinomas.

PMID- 19160107
TI  - Expression and significance of FRA-1 in non-small-cell lung cancer.
AB  - Fra-1 is thought to play an important role in tumorigenesis and progression. This
      study aimed to investigate the expression and significance of Fra-1 in non-small
      cell lung cancer (NSCLC). By analyzing with Western blot and
      immunohistochemistry, we found that Fra-1 is downregulated in NSCLC, compared
      with normal bronchial epithelium. Further, the low expression of Fra-1 correlates
      with advanced tumor stage and poor survival. Meanwhile, the distinct cytoplasmic
      location of Fra-1 was found in almost all immunoreactive cells. These findings
      reveal a potential nontranscriptional function of Fra-1, and indicate that Fra-1
      might play a role in the progression and prognosis of NSCLC.

PMID- 19160108
TI  - Treating in the dark: unanswered questions on costs and benefits of late line
      therapy for metastatic breast cancer.

PMID- 19160109
TI  - Decidual immune cell infiltrate in hydatidiform mole.
AB  - BACKGROUND: Hydatidiform mole is a gestational trophoblastic disease
      characterized by proliferation of the pregnancy-associated trophoblastic tissue.
      Complete hydatidiform mole is an entirely paternally derived lesion, and
      therefore, represents complete intrauterine allografts that can induce an altered
      maternal immune response Hypothesis: Here, we hypothesize that "the development
      of hydatidiform moles is associated with numeric alterations of the decidual
      immune cell infiltrate." MATERIALS AND METHODS: A total of 30 specimens (decidual
      tissue), entailing normal first trimester pregnancy terminations and complete
      hydatidiform moles (15 cases, each), were evaluated for immune cell infiltrate
      using immunohistological methods and monoclonal antibodies (CD20, CD68, and CD3
      for B cells, histiocytes/dendritic cells, and T cells, respectively). RESULTS:
      Groups of immune cells were seen in the decidual tissue of first trimester normal
      pregnancy terminations and hydatidiform moles. Compared to the decidual tissue of
      first trimester normal pregnancy terminations, the mean counts of the immune
      cells were statistically significantly higher (p< 0.05) in the decidual tissue of
      the hydatidiform moles (0.33 +/- 0.21 vs. 1.66 +/- 0.21 for CD20(+)B cells; 9.80
      +/- 1.57 vs. 13.14 +/- 1.16 for CD68(+) cells; and 12.92 +/- 3.46 vs. 23.85 +/-
      1.22 for CD3(+) cells for decidual tissue without and with molar changes,
      respectively). CONCLUSIONS: Hydatidiform moles are associated with numeric
      alterations of immune cell infiltrate. The numeric dominance of immune cells in
      the hydatidiform moles may reflect either non-specific or specific immunological
      processes. The possible pathogenetic and prognostic ramifications of our findings
      are open for further investigations.

PMID- 19160111
TI  - Morgagni on apoplexy in De Sedibus: a historical perspective.
AB  - This paper considers the historical significance of case reports on apoplexy and
      paralysis in Morgagni's De Sedibus et Causis Morborum. When autopsies became
      relatively common in the sixteenth century, Galen's speculation that apoplexy was
      caused by the accumulation of cold phlegm or black bile in the cerebral
      ventricles began to be questioned and was largely abandoned in the following
      century. The notion that the seats and causes of diseases are to be found in
      solid organs and not in the dyscrasia of humors gradually replaced many but not
      all humoral concepts. Morgagni's letters on apoplexy bolstered this "solidist"
      idea, but humoral physiology was still employed as a foundation for the treatment
      of apoplexy and to explain some aspects of the pathogenesis of this syndrome.
      Based on autopsy studies, Morgagni considered two principal forms of apoplexy,
      due to intracranial hemorrhage ("sanguineous apoplexy") and excessive
      intracranial fluid ("serous apoplexy"), to which he added a group that he judged
      to be separate from these two archetypes.

PMID- 19160112
TI  - Dr. William Thornton's views on sleep, dreams, and resuscitation.
AB  - William Thornton, MD, was a polymath who designed the Capitol of the U.S. Capital
      and the Octagon House, present home of the American Institute of Architecture. He
      was the founding director of the U.S. Patent Office. His collected papers, which
      are now preserved at the U.S. Library of Congress, though pruned by the wife who
      lived almost 40 years after him, are extensive and include comments on science,
      education, slavery, and politics. His views on sleep and dreaming and his
      concepts of resuscitation are reviewed as the opinions of an educated man early
      in the nineteenth century.

PMID- 19160113
TI  - Acetylcholine--from Vagusstoff to cerebral neurotransmitter.
AB  - This paper is concerned with some of the events in physiology that followed Otto
      Loewi's description of a substance that he named "Vagusstoff"; events that led
      eventually to the establishment of acetylcholine as a transmitter substance in
      the nervous system. Much of the work achieving this recognition of acetylcholine
      as a neurotransmitter took place in the middle third of the twentieth century; a
      period that witnessed the dislocation of many people as a result of National
      Socialist policies in Germany, that country's expansionist conquests, and the
      Second World War. A few of the people who were obliged to emigrate from Europe
      played prominent roles in these discoveries. This paper describes some of their
      achievements and, in a way, pays tribute to them.

PMID- 19160110
TI  - Chronic antioxidant therapy reduces oxidative stress in a mouse model of
      Alzheimer's disease.
AB  - Oxidative modifications are a hallmark of oxidative imbalance in the brains of
      individuals with Alzheimer's, Parkinson's and prion diseases and their respective
      animal models. While the causes of oxidative stress are relatively well
      documented, the effects of chronically reducing oxidative stress on cognition,
      pathology and biochemistry require further clarification. To address this, young
      and aged control and amyloid-beta protein precursor-over-expressing mice were fed
      a diet with added R-alpha lipoic acid for 10 months to determine the effect of
      chronic antioxidant administration on the cognition and neuropathology and
      biochemistry of the brain. Both wild type and transgenic mice treated with R
      alpha lipoic acid displayed significant reductions in markers of oxidative
      modifications. On the other hand, R-alpha lipoic acid had little effect on Y-maze
      performance throughout the study and did not decrease end-point amyloid-beta
      load. These results suggest that, despite the clear role of oxidative stress in
      mediating amyloid pathology and cognitive decline in ageing and AbetaPP
      transgenic mice, long-term antioxidant therapy, at levels within tolerable
      nutritional guidelines and which reduce oxidative modifications, have limited
      benefit.

PMID- 19160114
TI  - President Wilson's brain trust: Woodrow Wilson, Francis X. Dercum, and American
      neurology.
AB  - On October 2, 1919, President Woodrow Wilson suffered a stroke that paralyzed the
      left half of his body. Wilson's stroke forced the American public to confront
      stroke, and laypeople came to identify stroke as a nervous disorder, rather than
      a condition rooted solely in psychological phenomena. His medical care was
      overseen by Cary Grayson, his personal internist, and Francis X. Dercum, a
      remarkably accomplished neurologist from Philadelphia. Dercum was very involved
      in the treatment of the President, from the day of the stroke until years later.
      While the medical records have been destroyed, some basic facts of Wilson's
      treatment and rehabilitation can be inferred from the literature. Although
      Woodrow Wilson was an exceptional patient, his care, albeit administered by some
      of the most famous physicians of the era, was typical of the time. Therefore,
      this paper's approach to Wilson's 1919 stroke contextualizes the President's case
      into the larger scheme of early twentieth-century neurology.

PMID- 19160115
TI  - The pen nib and the bolt: the rhomboid fossa of the fourth ventricle or the
      symbol of the censorship of the press?

PMID- 19160116
TI  - Neurognostics question. Nerve, muscle, blood, toil, tears, and sweat: England's
      pioneering biophysicist, soldier, and statesman.

PMID- 19160123
TI  - Hypoglycemia in a patient with advanced Sezary syndrome.

PMID- 19160124
TI  - Acute lymphoblastic leukemia presenting with avascular necrosis of the elbow.

PMID- 19160125
TI  - MicroRNAs in the ontogeny of leukemias and lymphomas.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs with post-transcriptional regulatory
      functions. Their role in normal hematopoiesis is being elucidated by an
      increasing number of studies, revealing specific variations of the miRNome
      (defined as the full complement of miRNAs in a genome) during the commitment and
      development of the hematological stem cells in the different lineages.
      Aberrancies of the normal miRNome have also been well documented in almost all
      hematological malignancies, suggesting, in most cases, specific miRNA-signatures.
      Intriguingly, some of the miRNA-expression abnormalities described in leukemias
      and lymphomas can be interpreted on the basis of the miRNome variations during
      normal hematologic ontogeny, revealing their origin from the particular
      differentiation stage in which the hematopoietic differentiation has been
      'frozen' in the malignancy.

PMID- 19160126
TI  - Down-regulation of Notch-1 increases co-cultured Jurkat cell sensitivity to
      chemotherapy.
AB  - The bone marrow (BM) microenvironment plays a critical role in malignant cell
      growth, patient survival and response to chemotherapy in hematologic
      malignancies. However, the molecular mechanisms of BM stromal cells (BMSCs)
      mediated survival of tumor cell remain unclear. In this study, to further
      evaluate the role of Notch-1 in vivo microenvironment, we investigated the
      influence of inhibiting Notch-1 pathway by Notch-1 siRNA on Jurkat cells in the
      co-culture system. We found that Notch-1 signaling in Jurkat cells was further
      activated by interaction with BMSCs, which inhibited drug-induced apoptosis in
      Jurkat cells. Notch-1 siRNA down-regulated Notch-1 and restored drug-induced
      apoptosis in co-cultured Jurkat cells. The possible mechanism of restoration of
      sensitivity to chemotherapy could be associated with repressed Akt signaling. The
      results indicated that Notch-1 may be a potential mechanism of BMSCs involvement
      in the protection of hematopoietic malignant cells from drug-induced apoptosis.

PMID- 19160127
TI  - Reduced plasma all-trans retinoic acid level in a patient with Crohn's disease
      with acute promyelocytic leukemia.

PMID- 19160128
TI  - Could autism with mental retardation result from digenism and frequent de novo
      mutations?
AB  - The high concordance for autism symptoms in monozygotic twin-pairs compared to di
      zygotic twins and/or non-twin sib-ships suggests a high genetic determinism in
      autism. Those results have hypothesized multi-factorial determinism in accordance
      with family studies and mathematical models. However, linkage and association or
      candidate gene strategies have failed to-date to identify clearly involved
      mechanisms. Mental retardation (MR) is known as frequently associated to autism.
      Multiplex XLMR pedigrees have been reported with only one mutated patient having
      autism and MR: different X-located MR genes have been shown to be involved
      (NLGN4, MECP2, OPHN1, ZNF674 and FRAXA) which does not suggest that they could be
      "autism genes". Tuberous sclerosis studies and report of numerous autosomal
      domains shown deleted in MR-autistic subjects suggest that several autosomal
      dominant (AD) genes could be also involved in MR with autism. Whereas multiplex
      AD-MR families are rare, AD de novo mutations could explain numerous sporadic
      situations of non-specific MR and of autism with MR, in accordance with twin
      studies. Finally, we hypothesize that in those autistic subjects with mendelian
      MR, the XL-MR or AD-MR gene (G1) would pave the way for a second Mendelian factor
      (G2) responsible for autism symptoms.

PMID- 19160129
TI  - Believing in yourself.
AB  - The significance of believing in yourself might appear very obvious;
      nevertheless, belief in self is so important that it is worth repeating until it
      sinks into our sometimes unconvinced minds. This special state of believing in
      yourself reaches considerable proportions of support and help for the surgeon
      whether in training, early professional life, or experienced-especially when
      introduced with principles of self-worth, trust, and confidence. This essay
      reviews the essential understanding of the role of believing in yourself in the
      surgeon's career and professional life. Historical examples highlight pioneer
      surgeons who dealt with circumstances where self-belief was crucial in their
      advanced work. The goal is to make the surgeon a better professional and a better
      human being.

PMID- 19160130
TI  - De Humani Corporis Fabrica surgical revolution.
AB  - De Humani Corporis Fabrica (1543), by the Belgian anatomy master Andreas Vesalius
      (1514-1564), represents one of the most advanced surgical revolutions in history.
      The creation of an anatomy book that carefully and systematically introduced the
      structure of the human body in a way that was truthful to the findings of human
      dissection had never been accomplished before. No one challenged Galen's
      teachings as Vesalius did. De Humani Corporis Fabrica offered to the surgeon's
      world new knowledge and a systematic approach to human anatomy. The novel
      concepts and perspectives introduced by Vesalius constituted a real surgical
      revolution worthy of study in the annals of surgery.

PMID- 19160131
TI  - Protective effects of N-acetylcysteine and beta-glucan pretreatment on oxidative
      stress in cecal ligation and puncture model of sepsis.
AB  - This study was designed to compare the effect of pretreatment with N
      acetylcysteine (NAC) and beta -glucan (beta GLU) on inflammatory response in a
      rat model of sepsis. The study was performed in the animal laboratory of the
      Kahramanmaras Sutcu Imam University, School of Medicine. Forty rats were
      randomized into four groups (control, sham, NAC, and beta GLU). Control and Sham
      groups received saline or NAC (200 mg/kg, po) in the NAC group and beta GLU (50
      mg/kg, po) in the betaGLU group via intragastric gavage once a day for 10 days
      and 30 min prior to surgery. Sepsis was induced by cecal ligation and puncture
      (CLP) in rats. In the NAC, beta GLU, and control groups, a laparotomy was
      performed with the CLP procedure. In the sham group, laparotomy was performed and
      cecum was manipulated but not ligated or perforated. TNF-alpha and IL-6 levels
      were significantly elevated in the control group and decreased in the NAC and
      beta GLU groups. IL-10 levels were significantly increased in the beta GLU group
      (p < .05). Superoxide dismutase and catalase levels in the liver tissue were
      significantly increased in the NAC and beta GLU groups, whereas superoxide
      dismutase levels were higher in the beta GLU pretreatment group than the NAC
      pretreatment group (p < 0.05). Malondialdehyde levels in the liver tissue were
      significantly elevated in the control group and decreased in the NAC and beta GLU
      groups (p < .05). Prophylactic administration of NAC or beta GLU similarly
      ameliorated sepsis syndrome by reduction of the proinflammatory cytokines and
      increase of the anti-inflammatory cytokine levels and accession of cellular
      antioxidants, which protect cells from oxidative stress, thereby recruiting
      inflammatory cells into tissue.

PMID- 19160132
TI  - Influences of intestinal ligation on bacterial translocation and inflammatory
      response in rats with hemorrhagic shock: implications for damage control surgery.
AB  - Damage Control Surgery (DCS) treatment of rapid intestinal ligation to control
      the bowel spillage in severe abdominal trauma induces acute intestinal loop
      obstruction. The purpose of this study was to investigate the effects of
      intestinal ligation on bacterial translocation (BT) and inflammatory reaction
      under the condition of acute hemorrhagic shock and its probable pathophysiology.
      Escherichia coli TG1 labeled with green fluorescent protein was used to track BT
      by gavage to rats. Group Shock rats were subjected to hemorrhagic shock for 30
      minutes. Group Shock+Ligation (Shock+L) rats were subjected to hemorrhagic shock
      and following intestinal ligation. We found that hemorrhagic shock alone or in
      combination with intestinal ligation caused not only morphological damage to
      ileal mucosa, but also induced BT and promoted release of TNF-alpha, IL-6, and IL
      10 in serum and lymph. Ileal mucosa injuries and BT were significantly aggravated
      and cytokine levels in serum and lymph were significantly elevated in group
      Shock+L compared with group Shock. The positive proportions of bacterial culture
      and cytokine levels were significantly elevated in lymph compared with these in
      blood in both groups. By fluorescence microscope and XbaI restriction digestion
      analysis, we elucidated that the bacteria isolated from extraintestinal organs
      were the same bacteria we gavaged to the rats. We first confirmed that DCS
      treatment of rapid intestinal ligation under the condition of acute hemorrhagic
      shock leads to aggravated intestinal mucosa barrier injury and BT and elevated
      inflammatory response. The intestinal BT and immunoinflammatory factors may act
      through or mainly through lymph route.

PMID- 19160133
TI  - Differences in LPS and PepG induced release of inflammatory cytokines in
      orthopedic trauma.
AB  - Trauma is associated with immune paresis which may predispose to postoperative
      sepsis. We characterized the ex vivo cytokine responses to bacterial cell wall
      components in whole blood from 8 patients undergoing a major musculoskeletal
      trauma in the form of total hip replacement. Preoperatively, at the end of
      operation, and at days 1 and 6 postoperatively, patient blood was obtained,
      anticoagulated, and incubated at 37 degrees C in the presence of peptidoglycan
      (PepG) or lipopolysaccharide (LPS). Plasma cytokines were measured by enzyme
      immunoassay. The numbers of leucocytes, monocytes, and neutrophils were unchanged
      at the end of surgery, while there were significant increases at postoperative
      days 1 and 6. We observed significant reductions in tumor necrosis factor-alpha
      (TNF-alpha) and interleukin 10 (IL-10) responses to PepG at the end of surgery,
      which was disproportional to the nonsignificant reductions in circulating
      monocytes, suggesting a functional suppression. However, at postoperative day 1
      the responses were recovered. There were no significant changes in responses of
      TNF-alpha to LPS stimulation at the end of surgery, while there were significant
      depressions at postoperative days 1 and 6. The expression of IL-10 was
      significantly depressed at the end of surgery and at day 6. There were modest
      changes in PepG- and LPS-induced expression of interleukin 8 (IL-8) during the
      experiments. On the basis of these observations, we conclude that a
      musculoskeletal trauma is associated with reduced expression of TNF-alpha and IL
      10 by whole blood leucocytes when exposed to endotoxin, but there is a difference
      between gram-positive endotoxin (PepG) and gram-negative endotoxin (LPS).

PMID- 19160134
TI  - Assessment of wound healing in the alloxan-induced diabetic rabbit ear model.
AB  - The enhancement of diabetic wound healing represents a major clinical challenge
      to researchers. The challenge faced is to identify a suitable animal model that
      best represents the human situation. However, the majority of diabetic wound
      healing models are in rodents and are hindered by rapid contraction and thus do
      not reflect epithelial cell migration, as seen in the human wound. The alloxan
      induced diabetic rabbit model is a cheap, reproducible model and offers the
      advantage of providing a noncontractile avascular wound bed. This study aimed to
      compare the effects of acute hyperglycemia in the alloxan model to normal rabbit
      controls on wound healing, using methods of stereology. Alloxan was administered
      7 days prior to surgery. Four full-thickness punch biopsy wounds were created on
      each ear (n = 4). Wounds were excised at 7 and 14 days and prepared for
      stereological analysis from Masson's trichrome-stained histological sections. It
      was noted that the alloxan-treated animals showed an increase in the number of
      inflammatory cells and fibroblasts at 14 days. In addition, it was noted that the
      length density of blood vessels was reduced in the alloxan-induced diabetic
      rabbits, representing a greater radial diffusion distance between vessels and a
      less efficient network for nutrient exchange. This is the first study to take a
      stereological approach to defining the effects of diabetes mellitus on wound
      healing in a noncontractile model.

PMID- 19160135
TI  - Bone marrow-derived stromal cells (BMSCs) interact with fibroblasts in
      accelerating wound healing.
AB  - Bone marrow-derived stromal cells (BMSCs) exhibit extraordinary degree of
      plasticity and growth factor repertoire for which they have been investigated for
      repair and regeneration of damaged tissues, but have not been adequately examined
      for wound healing. The ability of BMSCs to accelerate healing of surgically
      inflicted cutaneous and fascial wounds was tested in vivo in rats and in vitro
      using a fibroblast monolayer wound model. Intravenous treatment with BMSCs
      augmented healing of both cutaneous and fascial wounds as determined by an
      increase in the biomechanical strength of wounds. In vitro experiments showed
      that incorporation of BMSCs in fibroblast monolayers accelerates the closure of
      mechanically disrupted monolayers, which was attributed to the enhanced migration
      of fibroblasts onto the denuded surfaces. Furthermore, culture medium conditioned
      by activated BMSCs promoted the closure of defects in monolayers and enhanced the
      proliferation/growth and directional migration (chemotaxis) of fibroblasts. This
      study demonstrates that BMSCs significantly augment healing of cutaneous and
      fascial wounds in vivo at least in part through interaction with fibroblasts in
      which BMSCs promote growth and chemotaxis of fibroblasts.

PMID- 19160136
TI  - Postimplant behavior of lightweight polypropylene meshes in an experimental model
      of abdominal hernia.
AB  - BACKGROUND: Over the years, reticular prostheses have undergone changes in their
      structure and composition to give rise to today's partially absorbable
      lightweight meshes. This study was designed to assess the biological and
      biomechanical behavior of these prostheses to establish whether they offer any
      advantages over nonabsorbable lightweight polypropylene prostheses. MATERIALS AND
      METHODS: 7 x 5 cm defects were created in the anterior abdominal wall of New
      Zealand White rabbits and repaired by securing different prostheses to the edges
      of the defect with a running 4/0 polypropylene suture. The lightweight
      biomaterials compared were two nonabsorbable meshes: Parietene and Optilene
      elastic, and two partially absorbable prostheses: Vypro II and Ultrapro. At 14
      and 90 days postimplant, tissue/prosthesis specimens were subjected to
      histological, immunohistochemical, shrinkage, and biomechanical analyses.
      RESULTS: Adhesion formation on the peritoneum-facing surface of the meshes was
      significantly less extensive in the meshes with absorbable components at 90 days
      postimplant. The newly formed tissue around the prosthetic filaments was
      comprised of collagen fibers, fibroblasts, blood vessels, and macrophages. The
      partially absorbable meshes showed higher macrophage proportions (due to remnants
      of absorbable material and their structure) than the nonabsorbable meshes at 90
      days, although differences were not significant. At 90 days postimplant, similar
      tensile strengths were recorded for all the implants. CONCLUSIONS: All the
      prosthetic materials induced good host tissue ingrowth, with no significant
      differences in tensile strength observed. Our findings suggest that partially
      absorbable lightweight prostheses could offer advantages over nonabsorbable
      lightweight meshes since less foreign material persists in the recipient,
      improving abdominal wall compliance.

PMID- 19160138
TI  - Understanding our limitations.

PMID- 19160137
TI  - Induction of rejection after small-for-size liver transplantation: size matters.
AB  - BACKGROUND: Reduced-size liver transplantation is associated with liver
      regeneration. This study was designed to analyze the influence of graft size on
      liver rejection and liver regeneration. METHODS: Reduced-size liver
      transplantations were performed in the rejecting ACI to Lewis and the graft
      acceptance BN to Lewis strain combination. The BN to Lewis control group was
      treated with the immunosuppressive drug FK506. RESULTS: An accelerated liver
      rejection in the ACI to Lewis strain combination was found in small-for-size
      partial liver grafts. Graft weight to recipient liver weight ratio (GW/RLW)
      showed a positive correlation with survival time. In the BN to Lewis strain
      combination, lethal rejection was seen in small-for-size partial liver grafts. A
      critical immunologic GW/RLW of 33% was calculated. In rats dying from lethal
      rejection, GW/RLW and survival time showed a positive correlation. However,
      GW/RLW showed a negative correlation with hepatocellular proliferation. In
      regenerating livers, MHC II upregulation was also observed in the control group.
      All control animals survived small-for-size liver transplantation. CONCLUSIONS:
      The relative graft size seems to be a decisive factor influencing the kinetic of
      liver rejection and the induction of liver rejection. Relative critical
      immunologic liver mass was determined to be 33%.

PMID- 19160139
TI  - Exercitatio Anatomica De Motus Cordis et Sanguinis in Animalibus surgical
      revolution.
AB  - William Harvey (1578-1657), renowned British physician, introduced to the world a
      unique scientific pradigm pertaining to the circulation of the blood. In 1628,
      his acclaimed work Exercitatio Anatomica De Motus Cordis et Sanguinis in
      Animalibus was published in Frankurt, Germany. Because of the discovery of the
      circulation, the medical world was forever changed afterwards! The incredible
      implications of Harvey's work on the yet-to-be developed surgical sciences in the
      centuries ahead make his outstanding contribution shine as a true surgical
      revolution. Without his knowledge and discovery, the development of surgery,
      particularly in the cardiac and vascular arena, would likely never have occurred.
      This work reviews the discovery of circulation within the context of the
      historical frame of earlier works that allowed the genius of William Harvey to
      complete his superb contributions to medicine.

PMID- 19160140
TI  - Nadroparine blunts lipopolysaccharide-induced hypothermia and behavioral
      depression in mice.
AB  - INTRODUCTION: Despite the use of appropriate antimicrobial therapy and intensive
      care support, sepsis remains a major cause of morbidity and mortality in surgical
      clinics. Low-molecular weight heparin treatment may reduce mortality and end
      organ failure in sepsis. The purpose of this study was to compare the effects of
      low-molecular weight heparins such as nadroparine, enoxaparine, and dalteparine
      on lipopolysaccharide-induced acute phase reaction in mice. METHODS:
      Lipopolysaccharide was injected intraperitoneally to produce a systemic
      inflammatory response and septic shock-like effects in adult male BALB/c mice.
      Mices were treated with low-molecular weight heparins (nadroparine, enoxaparine,
      dalteparine) and unfractioned heparin in different doses and times. Rectal
      temperature and spontaneous locomotor activity of the mice were evaluated.
      RESULTS: Lipopolysaccharide (1 mg/kg, intraperitoneal) produced a hypothermia
      that occurred 20 minutes after injection. Nadroparine pretreatment (23.75 U/kg,
      sc) 2 hours before lipopolysaccharide challenge, but not synchronous injection,
      inhibited the hypothermic response. Pretreatment with equivalent doses of
      enoxaparine or dalteparine had no effect on the hypothermia. The high dose of
      lipopolysaccharide (60 mg/kg, intraperitoneal) caused more profound hypothermia
      and also inhibited spontaneous locomotor activity 24 hours after injection.
      Synchronous nadroparine administration partially attenuated the hypothermia and
      significantly abolished the depression of spontaneous locomotor activity.
      CONCLUSIONS: The results suggest that some low-molecular weight heparins such as
      nadroparine might be beneficial in high-risk surgical patients because of their
      potential anti-inflammatory action, in addition to their efficiency in preventing
      thrombo-embolic complications.

PMID- 19160141
TI  - In vitro screening of different Allium sativum extracts on hydatid cysts
      protoscoleces.
AB  - This study was conducted to assess the protoscolicidal effect of garlic (Allium
      sativum) extract on protoscoleces of hydatid cysts in vitro. Viability of
      protoscoleces was determined, as the percent of viable protoscoleces to the total
      protoscoleces in 1 ml of the hydatid fluid, using eosin stain method. Four types
      of garlic extracts including: aquaus extract, chloroform extract (with two
      concentrations) and hydro-alcoholic extract along with cetrimide and silver
      nitrate as positive control, and normal saline as negative control, were used in
      this study. In vitro tests were performed at 37 degrees C with exposure times of
      30 minutes, one, two, four, and six hours. The protoscolecidal activity of the
      used materials was determined by counting of 250 protoscoleces. The mean percent
      and standard deviation (SD) of protoscolecidal activity of different used
      materials were as follows: cetrimide: 100 +/- 00, garlic chloroform extract with
      200 mg/ml concentration: 99.58 +/- 1.63, garlic chloroform extract with 100 mg/ml
      concentration: 96.06 +/- 7.28, silver nitrate: 95.91 +/- 7.11, garlic hydro
      alcoholic extract: 59.82 +/- 21.48, garlic simple extract: 40.91 +/- 18.1, and of
      saline: 16.01 +/- 6.25. The protoscolecidal activity increased by the time of
      exposure. Results of this study showed that chloroform extract of garlic with 200
      mg/ml concentration have the highest and simple extract of garlic have the lowest
      protoscolecidal activity.

PMID- 19160142
TI  - Functional cerebral venous outflow in swine and baboon: feasibility of an
      intracranial venous hypertension model.
AB  - INTRODUCTION: To evaluate the feasibility of performing a functional cerebral
      venous outflow blockage in two large animals species, the swine and the baboon,
      for elaboration of venous hypertension models. METHOD: Cerebral venous outflow
      pathways were identified on angiogram and venography of three swine and two
      baboons, and potential approaches to access these structures were assessed.
      Practicability of performing functional intracranial dural outflow blockage was
      tested. RESULTS: The main cerebral venous outflow route was the internal jugular
      vein in baboons and the paraspinal venous network in swine. Both animals had an
      additional venous outflow structure, the petrosquamous sinus. Access to
      intracranial venous sinuses was achieved through a percutaneous retrograde
      approach in baboon but not in swine, due to the absence of a direct connection
      between the dural structures and the internal jugular vein. A transcranial
      approach allowed to access dural venous structures in swine. In both models,
      partial and progressive venous sinus occlusion increased intracranial pressure,
      while preserving the animal's vital status. At 6 months, all animals are alive
      with no neurological deficits. CONCLUSION: Functional venous dural outflow
      blockage for elaboration of intracranial venous hypertension is feasible in both
      models. To be effective, the sinus blockage must be performed before the origin
      of the petrosquamous, an additional venous sinus seen in swine and baboon. The
      baboon has the greatest advantage of resembling human cerebral venous drainage,
      which enables an intracranial venous retrograde access. However, the transcranial
      approach remains a valuable option to access intracranial venous sinuses in
      swine.

PMID- 19160143
TI  - Evaluation of the effects of laparotomy and laparoscopy on the immune system in
      intra-abdominal sepsis--a review.
AB  - This review portrays the most common experimental models of intra-abdominal
      sepsis. Additionally, it outlines the facts that distinguish laparotomy from
      laparoscopy, in respect to the immune response, when comparing these two
      techniques in experimental models of intra-abdominal sepsis. It describes the
      consequences of pneumoperitoneum and trauma produced by laparoscopy or
      laparotomy, respectively, on bacterial translocation and immunity. Furthermore,
      we report the few efforts that have been made in clinical settings, where
      surgeons have attempted to utilize laparoscopy as a therapeutic module when
      treating peritonitis or sepsis of abdominal origin. Certainly there is a need for
      more research in order to fortify the role of pneumoperitoneum in sepsis of
      abdominal origin. It seems that minimally invasive surgery will inevitably gain
      acceptance by surgeons, as evidence points that by inflicting less trauma the
      healing response is expected to be more efficient, especially in septic patients.

PMID- 19160144
TI  - The effect of K-ATP channel blockage during erythropoietin treatment in renal
      ischemia-reperfusion injury.
AB  - ATP dependent K channels (K-ATP) take part in the Erythropoietin (EPO) induced
      cardioprotection but these channel activations have role in cytoprotective role
      of EPO in the renal ischemia reperfusion (IR) damage is still unknown. For this
      purpose rats were pretreated with EPO (500 IU/kg) and/or K-ATP channel blocker
      glibenclamide (40 mM/kg) i.p. before bilateral renal IR damage. Renal tissues
      were used for histological examination and measurement of caspase-3 and TNF-alpha
      levels. Renal functions were evaluated by glomerular filtration rate (GFR)
      fractional excretion of sodium (FENa) and potassium (FEK). Renal TNF-alpha and
      caspase-3 levels were decreased in both glibenclamide and EPO-treated IR rats
      compared to untreated rats. The protection afforded by the pretreatment with EPO
      alone was greater than that of administering glibenclamide alone. Application of
      glibenclamide at the same time partly abolished the cytoprotective effect of EPO
      treatment. K-ATP mediated cytoprotection is not the main mechanism of protective
      effect of EPO.

PMID- 19160145
TI  - Restoration of endocrine function and fertility with orthotopic tubal-ovarian
      allotransplant as the anatomical-functional unit in rabbits.
AB  - The aim of this study was to re-establish endocrine and reproductive function in
      tubal-ovariectomized rabbits using orthotopic tubal-ovary allotransplants (OT
      OA). Fifty-five New Zealand White nonconsanguineous rabbits were used and
      allocated into five experimental groups: Each group comprised donors submitted to
      right salpingo-oophorectomy that served as the donated allograft. In group 1 no
      cyclosporin (CsA) was administered and rabbits were submitted to left salpingo
      oophorectomy (LSO). Group 2 was the allotransplant group and did not receive CsA.
      Group 3 was the allotransplant group with CsA. They were submitted to bilateral
      salpingo-oophorectomy followed by OT-OA. CsA of 10 mg/kg/day was administered to
      rabbits for the first 21 days and 5 mg/kg/day for the remainder of the study.
      Group 4 received CsA just as for group 3 and was submitted to LSO. During the
      study the following were measured: estradiol (E2), progesterone (P4), follicle
      stimulating hormone (FSH), luteinizing hormone (LH), and histopathological study
      of the uteri, tubes, and ovaries. Groups 1, 3, and 4 showed a significant
      increase in serum E2 and P4 levels corresponding to the second week of gestation,
      compared to group 2 (p < .05). Group 2 showed a significant increase in serum LH
      and FSH levels during week 10 compared to serum LH and FSH levels in groups 1, 3,
      and 4 (p < .05). In group 3, three rabbits did not reject the allotransplant, one
      rabbit became pregnant, and endocrine function was re-established in two rabbits.
      It can be concluded that OT-OA together with CsA administration re-establishes
      endocrine function and fertility.

PMID- 19160147
TI  - The effects of splenectomy and splenic autotransplantation on plasma lipid
      levels.
AB  - PURPOSE: Atherosclerosis observations after splenectomy for trauma and
      hypersplenism suggests a possible role for the spleen in lipid metabolism. The
      authors examined the effects of splenectomy on serum lipids in rats and also
      cholesterol-fed rats with experimental atherosclerosis. METHODS: This study was
      designed on rats. The rats were divided into five groups: splenectomy, normal
      diet (SP-N, n: 8), splenectomy, cholesterol-fed groups (SP-C, n: 8), splenic
      autotransplantation after splenectomy, normal diet (SA-N, n: 8), splenic
      autotransplantation after splenectomy, cholesterol-fed groups (SA-C, n: 8) and
      sham groups (n: 8). Total triglyceride, total cholesterol, HDL (high-density
      lipoprotein), LDL (low-density lipoprotein), and VLDL (very low-density
      lipoprotein) levels were determined in 40 rats. The rats were classified into
      five groups based on the surgical procedures. The spleens were removed and then
      the rats were fed a normal diet in Group SP-N (n = 8). The spleens were removed
      and then the rats were fed a diet containing 1% cholesterol in Group SP-C (n =
      8). Splenectomy and splenic autotransplantations were performed and then the rats
      were fed a normal diet in Group SA-N (n = 8). Splenectomy and splenic
      autotransplantations were performed and then the rats were fed a diet containing
      1% cholesterol in Group SA-C (n = 8). The rats were sham-operated in the control
      group (Group S, n = 8). An active splenic function was shown in rats that
      underwent splenic autotransplantation in both groups by using Technicium 99 m
      sulphurcolloide sintiscan on day 30. Blood lipid levels were repeated 6 months
      later. RESULTS: There was no difference between pre- and postoperative lipid
      levels in the sham group and SA-N group (p >.05). All lipid levels including HDL
      were increased significantly in SP-C group (p <.05). Also VLDL and total
      tryglyceride levels were increased significantly in SP-N and SA-C groups (p
      <.05). CONCLUSIONS: This study showed that the spleen might have an important
      effect on lipid metabolism and splenic autotransplantation may be protective in
      conditions with increased lipid levels.

PMID- 19160146
TI  - Dexmedetomidine alters the cardiovascular response during infra-renal aortic
      cross-clamping in sevoflurane-anesthetized dogs.
AB  - Some properties of the volatile anesthetics, such as vasodilatation and
      myocardial depression, combined with the sympathetic inhibition that alpha2
      agonists can produce, may determine hemodynamic alterations during aortic
      surgery. The interaction between dexmedetomidine (DEX), an alpha2-agonist, and
      sevoflurane during aortic surgery is unknown. We studied the effects of DEX on
      hemodynamics and systemic oxygenation during aortic cross-clamping (Aox) and
      unclamping (UAox) in sevoflurane-anesthetized dogs. Twenty dogs were anesthetized
      with sevoflurane and were randomly assigned to two groups prior to Aox and UAox:
      control, n = 10, received saline infusion only, and DEX (1 microg x kg(-1) load
      followed by 1 microg x kg(-1) x h(-1) infusion), n = 10. Hemodynamic and
      oxygenation variables were measured at baseline, after saline or DEX loading
      dose, 20 and 40 min after Aox, and 20 and 40 min after UAox. After DEX
      administration, heart rate, cardiac index (CI) and systemic oxygen transport
      index (DO(2)I) were lower than in control group. Aox increased mean arterial
      pressure (MAP) and systemic vascular resistance index (SVRI) in both groups, but
      the effects were greater with DEX. CI, heart rate, and DO(2)I were lower, while
      central venous pressure (CVP) and pulmonary artery occlusion pressure were higher
      in DEX compared to control. After UAox, MAP, CVP and SVRI were maintained higher
      in DEX in relation to control. We conclude that in sevoflurane-anesthetized dogs
      DEX alters the cardiovascular response during aortic surgery.

PMID- 19160148
TI  - Principles of anesthesia monitoring--body temperature.
AB  - In this article we discuss the importance of monitoring body temperature. Some
      effects of hypothermia are covered, along with the benefits of careful
      monitoring. Also discussed are the basic use and application of the most common
      monitoring methods, as well as the methods we used to help maintain body
      temperature.

PMID- 19160150
TI  - Neurobehavioral characteristics of children with Duchenne muscular dystrophy.
AB  - This study investigated cognitive, metacognitive, and psychosocial aspects of
      neurobehavioral functioning in 22 boys with Duchenne muscular dystrophy (DMD) and
      18 unaffected siblings, all between the ages of 6 and 16 years. Probands and
      siblings completed the Wechsler Abbreviated Scale of Intelligence, as well as
      selected subtests from the Children's Memory Scale and from the Delis-Kaplan
      Executive Function System, while parents completed the Child Behavior Checklist
      and the Behavior Rating Inventory of Executive Function. Compared to siblings,
      probands demonstrated relative weaknesses on both verbal and nonverbal measures
      of delayed recall and response generation and were rated by parents as having
      more difficulties with social interaction, initiation, and adaptation. It is
      concluded that DMD is associated with mild but potentially significant
      difficulties in a range of neurobehavioral areas, likely related to deficient
      dystrophin levels in an integrated brain circuit that includes the cerebellum,
      hippocampus, and association neocortex.

PMID- 19160152
TI  - Stepwise radiofrequency ablation of Barrett's esophagus preserves esophageal
      inner diameter, compliance, and motility.
AB  - BACKGROUND AND AIM: Stepwise endoscopic circumferential and focal radiofrequency
      ablation is safe and effective for the eradication of Barrett's esophagus. In
      contrast to other techniques, radiofrequency ablation appears to avoid
      significant esophageal scarring or stenosis. Our aim was to evaluate whether
      radiofrequency ablation has an adverse effect on esophageal function in patients
      treated for Barrett's esophagus containing intramucosal cancer and/or high-grade
      dysplasia. METHODS: Twelve patients with Barrett's esophagus containing
      intramucosal cancer or high-grade dysplasia were included in the study. After
      endoscopic resection of visible abnormalities, stepwise circumferential and focal
      ablation were performed every 2 months up to a maximum of five sessions.
      Measurement of the inner diameter was performed at 1-cm intervals in the distal
      esophagus. Manometry was performed using a water-perfused sleeve catheter.
      Compliance was evaluated using the functional lumen imaging probe (FLIP),
      measuring eight cross-sectional areas within a saline-filled bag with two
      pressure side holes, one proximal to and one inside the bag. Esophageal sizing,
      manometry, and compliance were recorded in patients at baseline and at least 2
      months after the final ablation session. In addition, FLIP and manometry
      measurements were performed in 10 healthy volunteers. RESULTS: All patients
      achieved complete eradication of dysplasia and Barrett's esophagus, without
      severe complications or ablation-related stenoses. The esophageal diameter was
      unchanged by the ablation. Lower esophageal sphincter pressure and length and
      esophageal contraction amplitude before and after ablation were not significantly
      different. Baseline compliance was significantly different between healthy
      volunteers and Barrett's esophagus patients. Compliance was not, however,
      significantly changed by ablation. CONCLUSIONS: Stepwise circumferential and
      focal ablation of Barrett's esophagus is an effective and safe treatment modality
      for early Barrett's neoplasia that appears to preserve the functional
      characteristics of the esophagus.

PMID- 19160153
TI  - Differential diagnosis of intestinal Behcet's disease and Crohn's disease by
      colonoscopic findings.
AB  - BACKGROUND AND STUDY AIMS: Intestinal Behcet's disease and Crohn's disease are
      chronic inflammatory bowel diseases that are difficult to distinguish from each
      other. We investigated their colonoscopic features and identified simple and
      valuable strategies for differential diagnosis. PATIENTS AND METHODS: Between
      1995 and 2006, 250 consecutive patients with ulcers on colonoscopy (115 Behcet's,
      135 Crohn's cases) were reviewed. All patients with Behcet's fulfilled the
      criteria of the International Study Group for Behcet's Disease or of the Behcet's
      Disease Research Committee of Japan, while Crohn's disease was confirmed by
      clinicopathological data. Patients were randomly allocated to a training set (70
      %) or a validation set (30 %). Ulcer shapes, distributions, numbers, margins, and
      border contours, and the presence of aphthous, cobblestone, perianal, and
      strictured lesions were compared, in the training set. Univariate and
      multivariate analysis were performed, using the X2-test and logistic regression.
      In addition, a classification and regression tree (CART) was then used to
      generate simplified algorithms for differential diagnosis. RESULTS: Round shape,
      five or fewer in number, focal distributions, and absence of aphthous and
      cobblestone lesions were significantly dominant features in Behcet's disease,
      according to multivariate analysis of the training set. The CART-generated
      algorithms proposed sequential use of shape (round, irregular/geographic, or
      longitudinal) and distribution (focal single/focal multiple, or
      segmental/diffuse). Diagnosis of Behcet's disease in the validation set produced
      sensitivity, specificity, and negative and positive predictive values of 94.3 %,
      90.0 %, 94.7 %, and 89.2 %, respectively. Using the CART model, we made the
      correct diagnosis of intestinal Behcet's disease or Crohn's disease in 69 of 75
      patients (92 %). CONCLUSION: It was determined that round and longitudinal ulcers
      are suggestive of Behcet's disease and Crohn's disease, respectively.
      Irregular/geographic-shaped ulcers and focal distributions are suggestive of
      Behcet's disease, while segmental/diffuse lesions suggest Crohn's.

PMID- 19160154
TI  - Variable stiffness colonoscope versus regular adult colonoscope: meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND AND STUDY AIMS: The variable stiffness colonoscope (VSC) may have
      theoretical advantages over standard adult colonoscopes (SACs), though data are
      conflicting. We conducted a meta-analysis to compare the efficacies of the VSC
      and SAC. STUDY DESIGN: We searched Medline (1966 - 2008) and abstracts of
      gastroenterology scientific meetings in the 5 years to February 2008, only for
      randomized clinical trials (RCTs) of adult patients. Trial quality was assessed
      using the Delphi list. In a meta-analysis with a fixed effects model, cecal
      intubation rates, cecal intubation times, abdominal pain scores, sedation used,
      and use of ancillary maneuvers, were compared in separate analyses, using
      weighted mean differences (WMDs), standardized mean differences (SMDs), or odds
      ratios (ORs). RESULTS: Seven RCTs satisfied the inclusion criteria (1923
      patients), four comparing VSC with SAC procedures in adults, and three evaluating
      the pediatric VSC. There was no significant heterogeneity among the studies. The
      overall trial quality was adequate. Cecal intubation rate was higher with the use
      of VSC (OR = 2.08, 95 % confidence interval [CI] 1.29 to 3.36). The VSC was
      associated with lower abdominal pain scores and a decreased need for sedation
      during colonoscopy. Cecal intubation time was similar for the two colonscope
      types (WMD = - 0.21 minutes, 95 % CI - 0.85 to 0.43). Because of the nature of
      the intervention no studies were blinded. There was no universal method for using
      the VSC. CONCLUSIONS: Compared with the SAC, VSC use was associated with a higher
      cecal intubation rate, less abdominal pain, and decreased need for sedation.
      However, cecal intubation times were similar for the two colonoscope types.

PMID- 19160155
TI  - Experimental evaluation of photocrosslinkable chitosan hydrogel as injection
      solution for endoscopic resection.
AB  - BACKGROUND AND STUDY AIMS: Saline as an injection solution for endoscopic
      resection techniques has several disadvantages such as a short-lasting effect
      leading to a potentially higher risk of bleeding and perforation. The new
      substance of photocrosslinkable chitosan hydrogel in a DMEM/F12 medium (PCH) can
      be converted into an insoluble hydrogel by ultraviolet irradiation for 30 s, and
      was evaluated in two sets of animal experiments. METHODS: 18 pigs were used in
      the two parts of the study. First, mucosal resections were done with either PCH
      or hypertonic saline; the effects of both agents on wound healing were examined
      endoscopically and histologically. Second, in vivo degradation of PCH was
      examined using six pig stomachs. RESULT: PCH injection led to a longer-lasting
      elevation with clearer margins, compared with hypertonic saline, thus enabling
      precise endoscopic submucosal dissection (ESD) along the margins of the elevated
      mucosa. The endoscopic appearance after ESD was similar in both groups. PCH
      biodegradation was completed within 8 weeks according to endoscopic and
      histologic analyses. CONCLUSION: PCH is a promising agent for submucosal
      injection prior to various techniques of endoresection. It should be evaluated in
      clinical trials after biocompatibility testing for PCH is completed.

PMID- 19160156
TI  - Beyond NOTES: randomized controlled study of different methods of flexible
      endoscopic hemostasis of artificially induced hemorrhage, via NOTES access to the
      peritoneal cavity.
AB  - BACKGROUND AND STUDY AIM: Significant hemorrhage is a likely complication during
      natural orifice transluminal endoscopic surgery (NOTES) procedures. We tested
      three different prototype devices (involving endoscopic suturing, monopolar
      forceps, and forced argon plasma coagulation [FAPC]) for treatment of acute
      bleeding in a survival animal model. METHOD: Using transgastric access (TGA) or
      transvaginal access (TVA), the endoscope was introduced into the peritoneal
      cavity and the first side-branch of the gastroepiploic artery (1aGE) was cut
      before the different hemostatic methods were applied. RESULTS: Sutures could not
      be placed quickly enough before vision was inhibited. With monopolar forceps via
      TGA, the time to control bleeding was 10 - 140 s (mean 58 +/- 41 s) and with TVA
      it was 25 - 115 s (mean 57 +/- 26 s) (P = 0.54). It was not possible to stop the
      bleeding in 4/6 animals with TGA access and in 3/6 with TVA, and FAPC was needed
      to entirely stop it, taking a further 10 - 280 s (TGA mean 126 +/- 90 s, 34 - 242
      s; TVA mean 152 +/- 61 s; P = 0.42). Using FAPC with TGA took 4 - 72 s (mean 28
      +/- 20 s) to stop the bleeding, and 16 - 41 s (mean 24 +/- 9.4 s) with TVA ( P =
      0.64). As the FAPC technique was relatively so much better, additional treatment
      of bleeding from the main gastroepiploic artery (aGe) was added in four cases for
      each method of access; this was successful but took significantly longer, with
      TGA at 10 - 260 s and with TVA at 30 - 172 s (means 98 +/- 82, 117 +/- 54 s,
      respectively; not significant). CONCLUSION: Regarding the three methods tested,
      the new prototype FAPC device allowed hemostasis of notable bleeding from a major
      vessel even more quickly than forceps coagulation of a bleeding side branch. More
      studies are needed to further explore this potentially very valuable tool.

PMID- 19160157
TI  - Success and complication parameters for laparoscopic surgery: a benchmark for
      natural orifice transluminal endoscopic surgery.
AB  - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) currently
      represents an issue of particular interest among surgeons and
      gastroenterologists. The principle of NOTES is the reduction of the operative
      trauma by using natural orifices of the human body to access the abdominal
      cavity. Regarding the tendency to further minimization of the surgical trauma,
      NOTES may be considered as a logical step in the evolution of minimally invasive
      surgery. Pioneers of this technique regard NOTES as the successor to laparoscopic
      surgery in enabling surgeons and gastroenterologists to conduct scarless surgery.
      This might not only lead to better cosmetic results but also enhance the prospect
      of decreases in wound infections and incisional hernias, as well as reducing
      operative stress, postoperative immobility, and pain. MATERIAL AND METHODS: In
      this article the authors collect and review the existing literature concerning
      NOTES and establish a benchmark for the assessment of this new technique by
      stating results from conventional minimally invasive surgery as the gold
      standard. CONCLUSION: It is shown that publications investigating possible
      advantages or long-term results of NOTES are scarce. However, the investigation
      and verification of potential advantages and disadvantages represent the most
      important step in the development of a new technique. Only proven advantages
      would justify the broad implementation of a new technique in relation to its
      specific risks. Conventional laparoscopic surgery as the current standard of
      minimally invasive surgery will be the benchmark for NOTES with regard to most
      issues. Superiority of NOTES in at least several issues would be the best
      argument for its further implementation into clinical practice.

PMID- 19160158
TI  - Colonoscopy, tumors, and inflammatory bowel disease.

PMID- 19160159
TI  - Gastrointestinal bleeding.

PMID- 19160160
TI  - ERCP -- biliary.

PMID- 19160161
TI  - Natural orifice transluminal endoscopic surgery.

PMID- 19160163
TI  - Chromoendoscopy.

PMID- 19160165
TI  - [BVD eradication campaign in Switzerland: first results and outlook].
AB  - The Swiss BVD eradication campaign aims at eliminating the disease from the
      cattle population within a few years. During the initial phase from October 1st
      to December 31th 2008, all bovines will be individually tested and those found
      virus-positive slaughtered. In the following secondary phase, all newborn calves
      will be tested using ear notches taken on the occasion of the regular tagging
      process. From 2011 onwards, freedom of disease shall be confirmed based on a
      routine monitoring program, starting with antibody detection in milk of first
      lactating cows. In order to reduce the number of new infections, all bovines "not
      yet calved" and destined for shared mountain pastures were pretested in spring
      2008. The more than enthusiastic start led to an extension of testing far beyond
      the targeted segment, resulting in almost 600'000 or more than one third of the
      population being tested until the end of June, 1.1% of which with a positive
      result. This overwhelming kick-off was extremely demanding for all parties
      involved, but also allowed identifying many limiting steps that could be
      optimized in view of the initial phase.

PMID- 19160166
TI  - [Vigilance for veterinary medicinal products: declarations of suspected adverse
      reactions in the year 2007].
AB  - 163 reports of suspected adverse reactions were received in the year 2007: 111
      for veterinary medicinal (VMPs) and 52 for immunologic products. Half of the
      reported reactions for VMPs concerned either an antiparasitic drug (26%) or an
      antibiotic (24%). Reconversions (use in another target species or for another
      indication as registered) made the third most frequently mentioned group with 11
      reports. For immunologicals, half of the declarations were related to an adverse
      reaction in dogs, the most frequently reported reaction in companion animals
      being allergies. Moreover, 272 enquiries were received by the Swiss Toxicological
      Information Center in Zurich. Most of these were related to dogs (73%) and the
      number of enquiries regarding VMPs correlated positively with the most frequently
      used therapeutic classes like antiparasitics (47%) and anti-inflammatory drugs
      (23%). The complexity of proscessing reports regarding the detection of residues
      in milk after prescribed withdrawal times is discussed in detail. In conclusion,
      the year 2007 is seen as a consolidation of the established system with a
      tendency towards increase in the number of complex cases.

PMID- 19160167
TI  - [Cryptosporidiose (C. parvum) in a foal with diarrhea].
AB  - The protozoon parasite Cryptosporidium parvum is an important cause of diarrhea
      in farm animals, but it can also infect other animals and humans. In this case
      report, oocysts of Cryptosporidium spp. were microscopically detected by modified
      Ziehl-Neelsen staining in the feces of a 9 day old Arabian colt presented with
      yellowish, foul smelling, diarrhea and fever of 40 degrees C. PCR and sequencing
      of the isolate revealed C. parvum (bovine genotype). Hemato-chemical analysis of
      the foals blood revealed a marked hypogammaglobulinaemia (IgG 108mg/dl). The colt
      responded well to a supportive therapy and administration of plasma (until a
      gammaglobulin-concentration of 620 mg/dl was reached) and was released in good
      health from the clinic after 10 days. Follow-up testing for Cryptosporidium
      oocycsts remained negative. Cryptosporidiosis with life-threatening diarrhea is a
      rare diagnosis in foals in Switzerland. Immunodeficiency increases the risk for
      cryptosporidiosis. We hypothesize that the low concentration of gammaglobulins
      together with the weak INF-gamma response normally observed in young foals may
      have favored the clinical manifestation with diarrhea. Foals with diarrhea should
      be screened for cryptosporidia with specific tests.

PMID- 19160168
TI  - [First experiences with the continuous real-time glucose monitoring system
      (Guardian REAL-time CGMS) in a cat with diabetes mellitus].

PMID- 19160169
TI  - [Field study about the use of Enterisol Ileitis in a swine herd in Switzerland].

PMID- 19160171
TI  - [Veterinarian-patient confidentiality].

PMID- 19160172
TI  - [The Swiss social insurance law].

PMID- 19160173
TI  - WITHDRAWN: Amnioinfusion for meconium-stained liquor in labour.
AB  - BACKGROUND: Amnioinfusion aims to prevent or relieve umbilical cord compression
      during labour by infusing a solution into the uterine cavity. It is also thought
      to dilute meconium when present in the amniotic fluid and so reduce the risk of
      meconium aspiration. However, it may be that the mechanism of effect is that it
      corrects oligohydramnios (reduced amniotic fluid), for which thick meconium
      staining is a marker. OBJECTIVES: The objective of this review was to assess the
      effects of amnioinfusion for meconium-stained liquor on perinatal outcome. SEARCH
      STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register (October
      2001) and the Cochrane Controlled Trials Register (Issue 3, 2001) were searched.
      SELECTION CRITERIA: Randomised trials comparing amnioinfusion with no
      amnioinfusion for women in labour with moderate or thick meconium-staining of the
      amniotic fluid. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were
      assessed by one reviewer. MAIN RESULTS: Twelve studies, most involving small
      numbers of participants, were included. Under standard perinatal surveillance,
      amnioinfusion was associated with a reduction in the following: heavy meconium
      staining of the liquor (relative risk 0.03, 95% confidence interval 0.01 to
      0.15); variable fetal heart rate deceleration (relative risk 0.65, 95% confidence
      interval 0.49 to 0.88); and reduced caesarean section overall (relative risk
      0.82, 95% confidence interval 0.69 to 1.97). No perinatal deaths were reported.
      Under limited perinatal surveillance, amnioinfusion was associated with a
      reduction in the following: meconium aspiration syndrome (relative risk 0.24, 95%
      confidence interval 0.12 to 0.48); neonatal hypoxic ischaemic encephalopathy
      (relative risk 0.07, 95% confidence interval 0.01 to 0.56) and neonatal
      ventilation or intensive care unit admission (relative risk 0.56, 95% confidence
      interval 0.39 to 0.79); there was a trend towards reduced perinatal mortality
      (relative risk 0.34, 95% confidence interval 0.11 to 1.06). AUTHORS' CONCLUSIONS:
      Amnioinfusion is associated with improvements in perinatal outcome, particularly
      in settings where facilities for perinatal surveillance are limited. The trials
      reviewed are too small to address the possibility of rare but serious maternal
      adverse effects of amnioinfusion.

PMID- 19160174
TI  - Clozapine versus typical neuroleptic medication for schizophrenia.
AB  - BACKGROUND: Long-term drug treatment of schizophrenia with typical antipsychotics
      has limitations: 25 to 33% of patients have illnesses that are treatment
      resistant. Clozapine is an antipsychotic drug, which is claimed to have superior
      efficacy and to cause fewer motor adverse effects than typical drugs for people
      with treatment-resistant illnesses. Clozapine carries a significant risk of
      serious blood disorders, which necessitates mandatory weekly blood monitoring at
      least during the first months of treatment. OBJECTIVES: To evaluate the effects
      of clozapine compared with typical antipsychotic drugs in people with
      schizophrenia. SEARCH STRATEGY: For the current update of this review (March
      2006) we searched the Cochrane Schizophrenia Group Trials Register. SELECTION
      CRITERIA: All relevant randomised clinical trials (RCTs). DATA COLLECTION AND
      ANALYSIS: We extracted data independently. For dichotomous data we calculated
      relative risks (RR) and their 95% confidence intervals (CI) on an intention-to
      treat basis, based on a fixed-effect model. We calculated numbers needed to
      treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated
      weighted mean differences (WMD) again based on a fixed-effect model. MAIN
      RESULTS: We have included 42 trials (3950 participants) in this review. Twenty
      eight of the included studies are less than 13 weeks in duration, and, overall,
      trials were at significant risk of bias. We found no significant difference in
      the effects of clozapine and typical neuroleptic drugs for broad outcomes such as
      mortality, ability to work or suitability for discharge at the end of the study.
      Clinical improvements were seen more frequently in those taking clozapine
      (n=1119, 14 RCTs, RR 0.72 CI 0.7 to 0.8, NNT 6 CI 5 to 8). Also, participants
      given clozapine had fewer relapses than those on typical antipsychotic drugs
      (n=1303, RR 0.62 CI 0.5 to 0.8, NNT 21 CI 15 to 49). BPRS scores showed a greater
      reduction of symptoms in clozapine-treated patients, (n=1145, 16 RCTs, WMD -4.22
      CI -5.4 to -3.1), although the data were heterogeneous (Chi(2) 0.0001, I(2) 66%).
      Short-term data from the SANS negative symptom scores favoured clozapine (n=196,
      5 RCTs, WMD -5.92 CI -7.8 to -4.1). We found clozapine to be more acceptable in
      long-term treatment than conventional antipsychotic drugs (n=982, 16 RCTs, RR
      0.60 CI 0.5 to 0.7, NNT 15 CI 12 to 20). Blood problems occurred more frequently
      in participants receiving clozapine (3.2%) compared with those given typical
      antipsychotics (0%) (n=1031, 13 RCTs, RR 7.09 CI 2.0 to 25.6). Clozapine
      participants experienced more drowsiness, hypersalivation, or temperature
      increase, than those given conventional neuroleptics. However, clozapine patients
      experienced fewer motor adverse effects (n=1433, 18 RCTs, RR 0.58 CI 0.5 to 0.7,
      NNT 5 CI 4 to 6).The clinical effects of clozapine were more pronounced in
      participants resistant to typical neuroleptics in terms of clinical improvement
      (n=370, 4 RCTs, RR 0.71 CI 0.6 to 0.8, NNT 4 CI 3 to 6) and symptom reduction.
      Thirty-four per cent of treatment-resistant participants had a clinical
      improvement with clozapine treatment. AUTHORS' CONCLUSIONS: Clozapine may be more
      effective in reducing symptoms of schizophrenia, producing clinically meaningful
      improvements and postponing relapse, than typical antipsychotic drugs - but data
      are weak and prone to bias. Participants were more satisfied with clozapine
      treatment than with typical neuroleptic treatment. The clinical effect of
      clozapine, however, is, at least in the short term, not reflected in measures of
      global functioning such as ability to leave the hospital and maintain an
      occupation. The short-term benefits of clozapine have to be weighed against the
      risk of adverse effects. Within the context of trials, the potentially dangerous
      white blood cell decline seems to be more frequent in children and adolescents
      and in the elderly than in young adults or people of middle-age.The existing
      trials have largely neglected to assess the views of participants and their
      families on clozapine. More community-based long-term randomised trials are
      needed to evaluate the efficacy of clozapine on global and social functioning as
      trials in special groups such as people with learning disabilities.

PMID- 19160175
TI  - Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn's disease.
AB  - BACKGROUND: The therapeutic role of 6-mercaptopurine and azathioprine remains
      controversial due to their perceived relatively slow-acting effect and adverse
      effects. A meta-analysis was performed to evaluate the efficacy of these agents
      for the maintenance of remission of quiescent Crohn's disease. OBJECTIVES: To
      assess the efficacy of azathioprine and 6-mercaptopurine for maintenance of
      remission in quiescent Crohn's disease. SEARCH STRATEGY: Pertinent studies were
      selected using the MEDLINE data base (1966-May 1998), the Cochrane Controlled
      Trials Register, the Inflammatory Bowel Disease register, as well as abstracts
      from major gastrointestinal research meetings and references from published
      articles and review. This search strategy was updated (1998-May 2008) using the
      MEDLINE, EMBASE and International Pharmaceutical Abstracts databases, the
      Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD group
      Specialized Trials Register. SELECTION CRITERIA: Randomized, double-blind,
      placebo-controlled trials of oral azathioprine or 6-mercaptopurine involving
      adult patients (> 18 years) with quiescent Crohn's disease. DATA COLLECTION AND
      ANALYSIS: Data were extracted by three independent observers (EP, MC, LRS) based
      on the intention to treat principle. Peto odds ratios and 95% confidence
      intervals for maintenance of remission, steroid sparing, and withdrawals due to
      adverse effects were calculated. Numbers needed to treat or harm (NNT, NNH
      respectively) for the maintenance of remission, steroid sparing, and withdrawals
      due to adverse effects were also determined. MAIN RESULTS: Seven trials of
      azathioprine therapy and one of 6-mercaptopurine were included in the review.
      Azathioprine and 6-mercaptopurine had a positive effect on maintaining remission.
      The Peto odds ratio (OR) for maintenance of remission with azathioprine was 2.32
      (95% CI 1.55 to 3.49) with a NNT of 6. The Peto OR for maintenance of remission
      with 6-mercaptopurine was 3.32 (95% CI 1.40 to 7.87) with a of 4. Higher doses of
      azathioprine improved response. A steroid sparing effect with azathioprine was
      noted, with a Peto OR of 5.22 (95% CI 1.06 to 25.68) and NNT of 3 for quiescent
      disease. Withdrawals due to adverse events were more common in patients treated
      with azathioprine (Peto OR 3.74; 95% CI 1.48 to 9.45, NNH = 20) than with
      placebo. AUTHORS' CONCLUSIONS: Azathioprine and 6-mercaptopurine are more
      effective than placebo for maintenance of remission in Crohn's disease. Higher
      response rates were obtained with azathioprine than 6-mercaptopurine. However,
      the one study evaluating 6-mercaptopurine used a relatively low dose of the drug.
      Future studies should look at the effect of higher doses of 6-mercaptopurine.
      There is weak evidence for a steroid sparing effect with azathioprine treatment.

PMID- 19160176
TI  - Episiotomy for vaginal birth.
AB  - BACKGROUND: Episiotomy is done to prevent severe perineal tears, but its routine
      use has been questioned. The relative effects of midline compared with midlateral
      episiotomy are unclear. OBJECTIVES: The objective of this review was to assess
      the effects of restrictive use of episiotomy compared with routine episiotomy
      during vaginal birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (March 2008). SELECTION CRITERIA: Randomized
      trials comparing restrictive use of episiotomy with routine use of episiotomy;
      restrictive use of mediolateral episiotomy versus routine mediolateral
      episiotomy; restrictive use of midline episiotomy versus routine midline
      episiotomy; and use of midline episiotomy versus mediolateral episiotomy. DATA
      COLLECTION AND ANALYSIS: The two review authors independently assessed trial
      quality and extracted the data. MAIN RESULTS: We included eight studies (5541
      women). In the routine episiotomy group, 75.15% (2035/2708) of women had
      episiotomies, while the rate in the restrictive episiotomy group was 28.40%
      (776/2733). Compared with routine use, restrictive episiotomy resulted in less
      severe perineal trauma (relative risk (RR) 0.67, 95% confidence interval (CI)
      0.49 to 0.91), less suturing (RR 0.71, 95% CI 0.61 to 0.81) and fewer healing
      complications (RR 0.69, 95% CI 0.56 to 0.85). Restrictive episiotomy was
      associated with more anterior perineal trauma (RR 1.84, 95% CI 1.61 to 2.10).
      There was no difference in severe vaginal/perineal trauma (RR 0.92, 95% CI 0.72
      to 1.18); dyspareunia (RR 1.02, 95% CI 0.90 to 1.16); urinary incontinence (RR
      0.98, 95% CI 0.79 to 1.20) or several pain measures. Results for restrictive
      versus routine mediolateral versus midline episiotomy were similar to the overall
      comparison. AUTHORS' CONCLUSIONS: Restrictive episiotomy policies appear to have
      a number of benefits compared to policies based on routine episiotomy. There is
      less posterior perineal trauma, less suturing and fewer complications, no
      difference for most pain measures and severe vaginal or perineal trauma, but
      there was an increased risk of anterior perineal trauma with restrictive
      episiotomy.

PMID- 19160177
TI  - Multiple versus single doses of exogenous surfactant for the prevention or
      treatment of neonatal respiratory distress syndrome.
AB  - BACKGROUND: Randomized controlled trials have demonstrated the efficacy of
      surfactant therapy in the treatment of infants at risk for or having respiratory
      distress syndrome (RDS). Due to surfactant inactivation, multiple doses of
      surfactant may lead to improved outcome. OBJECTIVES: To determine the effect of
      multiple doses of exogenous surfactant compared to single doses of exogenous
      surfactant on mortality and complications of prematurity in premature infants at
      risk for or having respiratory distress syndrome. SEARCH STRATEGY: For the
      initial search in 1999, searches were made of the Oxford Database of Perinatal
      Trials, Medline (MeSH terms: pulmonary surfactant; limits: age groups, newborn
      infant; publication type, clinical trials), previous reviews including cross
      references, abstracts, conference and symposia proceedings, expert informants,
      and journal hand searching in the English language.In June 2008, the searches
      were updated including Medline, Cinhal and Embase using similar terms as the
      original search. SELECTION CRITERIA: Randomized controlled trials comparing a
      policy of multiple doses of surfactant to a policy of single doses of surfactant
      extract in premature infants at risk for or having respiratory distress syndrome
      were considered for this review. DATA COLLECTION AND ANALYSIS: Data on clinical
      outcomes including pneumothorax, patent ductus arteriosus, necrotizing
      enterocolitis, intraventricular hemorrhage (all intraventricular hemorrhage and
      severe intraventricular hemorrhage), bronchopulmonary dysplasia, retinopathy of
      prematurity, and mortality were excerpted by the both reviewers (R. Soll; E.
      Ozek). For this update additional data were sought on pulmonary hemorrhage,
      periventricular leukomalacia, neurodevelopmental follow-up, rehospitalization for
      pulmonary reasons,and reactive airway disease. Data were analyzed according to
      the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Three trials
      were identified that met study criteria. Two studies were randomized controlled
      trials of multiple vs. single dose animal derived surfactant extract in infants
      with established respiratory distress syndrome. Meta-analysis of these trials
      suggests a reduction in the risk of pneumothorax (typical relative risk 0.51, 95%
      CI 0.30, 0.88; typical risk difference-0.09, 95% CI -0.15, -0.02) and a trend
      towards a reduction in the risk of mortality (typical relative risk 0.63, 95% CI
      0.39, 1.02; typical risk difference -0.07, 95% CI -0.14, 00.00).One study of
      multiple vs. single dose synthetic surfactant in infants at high risk of
      respiratory distress syndrome was identified. This study reported a decrease in
      NEC (relative risk 0.20, 95% CI 0.08, 0.51; risk difference-0.05, 95% CI -0.07, 
      0.02) and mortality (relative risk 0.56, 95% CI 0.39, 0.81; risk difference-0.07,
      95% CI -0.12, -0.03)No data on long-term neurological or pulmonary outcome were
      reported.No complications associated with multiple dose treatment were reported
      in the identified trials. AUTHORS' CONCLUSIONS: In infants with established
      respiratory distress, a policy of multiple doses of animal derived surfactant
      extract resulted in greater improvements regarding oxygenation and ventilatory
      requirements, a decreased risk of pneumothorax and a trend toward improved
      survival.In infants at high risk of respiratory distress, a policy of multiple
      doses of synthetic surfactant resulted in greater improvements regarding
      oxygenation and ventilatory requirements, a decreased risk of NEC and decreased
      mortality.The ability to give multiple doses of surfactant to infants with
      ongoing respiratory insufficiency leads to improved clinical outcome and appears
      to be the most effective treatment policy.

PMID- 19160178
TI  - Compression for venous leg ulcers.
AB  - BACKGROUND: Around one percent of people in industrialised countries will suffer
      from a leg ulcer at some time. The majority of these leg ulcers are due to
      problems in the veins, resulting in an accumulation of blood in the legs. Leg
      ulcers arising from venous problems are called venous (varicose or stasis)
      ulcers. The main treatment has been a firm compression garment (bandage or
      stocking) in order to aid venous return. There is a large number of compression
      garments available and it is unclear whether they are effective in treating
      venous ulcers and which compression garment is the most effective. OBJECTIVES: To
      undertake a systematic review of all randomised controlled trials of the clinical
      effectiveness of compression bandage or stocking systems in the treatment of
      venous leg ulceration.Specific questions addressed by the review are:1. Does the
      application of compression bandages or stockings aid venous ulcer healing? 2.
      Which compression bandage or stocking system is the most effective? SEARCH
      STRATEGY: For this update we searched the Cochrane Wounds Group Specialised
      Register (14/10/08); The Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library Issue 4 2008); Ovid MEDLINE (1950 to October Week 1 2008);
      Ovid EMBASE (1980 to 2008 Week 41) and Ovid CINAHL (1982 to October Week 1 2008).
      No date or language restrictions were applied. SELECTION CRITERIA: Randomised
      controlled trials recruiting people with venous leg ulceration that evaluated any
      type of compression bandage system or compression hosiery were eligible for
      inclusion. Comparators included no compression (e.g. primary dressing alone, non
      compressive bandage) or an alternative type of compression. Trials had to report
      an objective measure of ulcer healing in order to be included (primary outcome
      for the review). Secondary outcomes of the review included ulcer recurrence,
      costs, quality of life, pain, adverse events and withdrawals. There was no
      restriction on date, language or publication status of trials. DATA COLLECTION
      AND ANALYSIS: Details of eligible studies were extracted and summarised using a
      data extraction table. Data extraction was performed by one review author and
      verified independently by a second review author. MAIN RESULTS: Overall, 39 RCTs
      reporting 47 comparisons were included.Review question 1: there was reasonable
      evidence from seven RCTs that venous ulcers heal more rapidly with compression
      than without.Review question 2: findings from six trials of single-component
      compression suggested that this strategy was less effective than multi-component
      compression. Evidence from compression systems with two components (3 trials) and
      three components (4 trials) suggested better outcomes when an elastic component
      was included. Different versions of compression with four-components (based on
      the Charing Cross four-layer bandage system) have similar effectiveness (3
      trials). Compression with four components (variants of the Charing Cross four
      layer bandage) is more effective than multi-component compression that includes a
      short-stretch bandage (6 trials). It is difficult to determine the relative
      effectiveness of the four-layer bandage compared with paste bandage systems
      because of differences in the paste systems (5 trials). There was no difference
      in effectiveness between the adjustable compression boot and compression bandages
      (2 trials) or between single-layer compression stockings and paste bandages (2
      trials). Two-layer stockings appeared more effective than the short-stretch
      bandage (2 trials). The relative effectiveness of tubular compression when
      compared with compression bandages was not clear from current evidence (2
      trials).Three trials reported ulcer recurrence; because of sparseness of data and
      trials not being primarily designed to assess this outcome, firm conclusions
      could not be drawn. Although several trials included cost data, only one reported
      a rigorously conducted cost-effectiveness analysis with findings suggesting that
      the four-layer bandage was more cost-effective than multi-component compression
      comprising a short-stretch bandage. Seven trials assessed health-related quality
      of life and none observed significant differences between treatment groups.
      Several trials evaluated pain either as a stand-alone outcome, or as part of the
      assessment of adverse events. In general, the data did not indicate clear
      differences between treatment groups. It is possible that stockings could be
      associated with less pain than bandages but in view of scarcity of available data
      this requires further evaluation. Many of the trials reported adverse events and
      / or withdrawals. Overall, these outcomes appeared similar across different
      treatment groups. AUTHORS' CONCLUSIONS: Compression increases ulcer healing rates
      compared with no compression. Multi-component systems are more effective than
      single-component systems. Multi-component systems containing an elastic bandage
      appear more effective than those composed mainly of inelastic constituents.

PMID- 19160180
TI  - Surgery or embolisation for varicoceles in subfertile men.
AB  - BACKGROUND: A varicoceles is a meshwork of distended blood vessels in the
      scrotum, usually left-sided, due to dilatation of the spermatic vein. Although
      the concept that varicoceles causes, and varicocelectomy cures, male subfertility
      has been around for almost fifty years, the mechanisms by which varicoceles would
      affect fertility have not yet been satisfactorily explained, and neither have the
      mechanisms by which varicocelectomy would restore fertility. Furthermore, it has
      been questioned whether a causal relation exists at all between the distension of
      the pampiniform plexus and impairment of fertility. OBJECTIVES: To evaluate the
      effect of varicoceles treatment on pregnancy rate in subfertile couples. SEARCH
      STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group
      Trials Register (12 Sept 2003 and October 2007), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library Issue 1, 2004 and Issue 4, 2007), MEDLINE
      (January 1966 to October 2007), EMBASE (January 1985 to October 2007) and
      reference lists of articles. In addition, we handsearched specialist journals in
      the field from their first issue until 2007. We also checked cross-references,
      references from review articles and contacted researchers in the field. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) were included if they were relevant
      to the clinical question posed, if they reported pregnancy rates as an outcome
      measure, and if they reported data in treated (surgical ligation or radiological
      embolisation of the internal spermatic vein) and untreated groups. DATA
      COLLECTION AND ANALYSIS: Nine studies met the inclusion criteria for the original
      review. One was an extension of a previously published study, which left eight
      studies for analysis. All eight only included men from couples with subfertility
      problems; one excluded men with sperm counts less than 5 million per mL and one
      men with sperm counts less than 2 million per mL, with or without progressive
      motility of less than 10%. Two trials involving clinical varicoceles included
      some men with normal semen analysis. Three studies specifically addressed only
      men with subclinical varicoceles. Two authors independently screened potentially
      relevant trials. Any differences of opinion were resolved by consensus (none
      occurred for this review). Studies were excluded from meta-analysis if they made
      comparisons other than those specified above. MAIN RESULTS: The combined Peto
      odds ratio (OR) of the eight studies is 1.10 (95%CI 0.73 to 1.68), indicating no
      benefit of varicoceles treatment over expectant management in subfertile couples
      in whom varicoceles in the man is the only abnormal finding. AUTHORS'
      CONCLUSIONS: There is no evidence that treatment of varicoceles in men from
      couples with otherwise unexplained subfertility improves the couple's chance of
      conception.

PMID- 19160179
TI  - Early discharge hospital at home.
AB  - BACKGROUND: 'Early discharge hospital at home' is a service that provides active
      treatment by health care professionals in the patient's home for a condition that
      otherwise would require acute hospital in-patient care. If hospital at home were
      not available then the patient would remain in an acute hospital ward.
      OBJECTIVES: To determine, in the context of a systematic review and meta
      analysis, the effectiveness and cost of managing patients with early discharge
      hospital at home compared with in-patient hospital care. SEARCH STRATEGY: We
      searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group
      Register , MEDLINE (1950 to 2008), EMBASE (1980 to 2008), CINAHL (1982 to 2008)
      and EconLit through to January 2008. We checked the reference lists of articles
      identified for potentially relevant articles. SELECTION CRITERIA: Randomised
      controlled trials recruiting patients aged 18 years and over. Studies comparing
      early discharge hospital at home with acute hospital in-patient care. Evaluations
      of obstetric, paediatric and mental health hospital at home schemes are excluded
      from this review. DATA COLLECTION AND ANALYSIS: Two authors independently
      extracted data and assessed study quality. Our statistical analyses were done on
      an intention-to-treat basis. We requested individual patient data (IPD) from
      trialists, and relied on published data when we did not receive trial data sets
      or the IPD did not include the relevant outcomes. For the IPD meta-analysis,
      where at least one event was reported in both study groups in a trial, Cox
      regression models were used to calculate the log hazard ratio and its standard
      error for mortality and readmission separately for each data set. The calculated
      log hazard ratios were combined using fixed-effect inverse variance meta
      analysis. MAIN RESULTS: Twenty-six trials were included in this review [n =
      3967]; 21 were eligible for the IPD meta-analysis and 13 of the 21 trials
      contributed data [1899/2872; 66%]. For patients recovering from a stroke and
      elderly patients with a mix of conditions there was insufficient evidence of a
      difference in mortality between groups (adjusted HR 0.79, 95% CI 0.32 to 1.91; N
      = 494; and adjusted HR 1.06, 95% CI 0.69 to 1.61; N = 978). Readmission rates
      were significantly increased for elderly patients with a mix of conditions
      allocated to hospital at home (adjusted HR 1.57; 95% CI 1.10 to 2.24; N = 705).
      For patients recovering from a stroke and elderly patients with a mix of
      conditions respectively, significantly fewer people allocated to hospital at home
      were in residential care at follow up (RR 0.63; 95% CI 0.40 to 0.98; N = 4
      trials; RR 0.69, 95% CI 0.48 to 0.99; N =3 trials). Patients reported increased
      satisfaction with early discharge hospital at home. There was insufficient
      evidence of a difference for readmission between groups in trials recruiting
      patients recovering from surgery. Evidence on cost savings was mixed. AUTHORS'
      CONCLUSIONS: Despite increasing interest in the potential of early discharge
      hospital at home services as a cheaper alternative to in-patient care, this
      review provides insufficient objective evidence of economic benefit or improved
      health outcomes.

PMID- 19160181
TI  - On-site mental health workers delivering psychological therapy and psychosocial
      interventions to patients in primary care: effects on the professional practice
      of primary care providers.
AB  - BACKGROUND: Mental health problems are common in primary care and mental health
      workers (MHWs) are increasingly working in this setting delivering psychological
      therapy and psychosocial interventions to patients. In addition to treating
      patients directly, the introduction of on-site MHWs represents an organisational
      change that may lead to changes in the clinical behaviour of primary care
      providers (PCPs). OBJECTIVES: To assess the effects of on-site MHWs delivering
      psychological therapy and psychosocial interventions in primary care on the
      clinical behaviour of primary care providers (PCPs). SEARCH STRATEGY: The
      following sources were searched in 1998: the Cochrane Effective Practice and
      Organisation of Care Group Specialised Register, the Cochrane Controlled Trials
      Register, MEDLINE, EMBASE, PsycINFO, CounselLit, NPCRDC skill-mix in primary care
      bibliography, and reference lists of articles. Additional searches were conducted
      in February 2007 using the following sources: MEDLINE, EMBASE, PsycINFO, CINAHL,
      and Cochrane Central Register of Clinical Trials (CENTRAL) (The Cochrane
      Library). SELECTION CRITERIA: Randomised trials, controlled before and after
      studies, and interrupted time series analyses of MHWs working alongside PCPs in
      primary care settings. The outcomes included objective measures of PCP behaviours
      such as consultation rates, prescribing, and referral. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted data and assessed study
      quality. MAIN RESULTS: Forty-two studies were included in the review. There was
      evidence that MHWs caused significant reductions in PCP consultations
      (standardised mean difference -0.17, 95% CI -0.30 to -0.05), psychotropic
      prescribing (relative risk 0.67, 95% CI 0.56 to 0.79), prescribing costs
      (standardised mean difference -0.22, 95% CI -0.38 to -0.07), and rates of mental
      health referral (relative risk 0.13, 95% CI 0.09 to 0.20) for the patients they
      were seeing. In controlled before and after studies, the addition of MHWs to a
      practice did not affect prescribing behaviour towards the wider practice
      population and there was no consistent pattern to the impact on referrals in the
      wider patient population. AUTHORS' CONCLUSIONS: This review provides some
      evidence that MHWs working in primary care to deliver psychological therapy and
      psychosocial interventions cause a significant reduction in PCP behaviours such
      as consultations, prescribing, and referrals to specialist care. However, the
      changes are modest in magnitude, inconsistent, do not generalise to the wider
      patient population, and their clinical or economic significance is unclear.

PMID- 19160182
TI  - WITHDRAWN: Systems for routine surveillance in people with diabetes mellitus.
AB  - BACKGROUND: There is wide variation in the extent of general practice involvement
      in diabetes care. OBJECTIVES: To assess the effects of involving primary care
      professionals in the routine review and surveillance for complications of people
      with established diabetes mellitus compared with secondary care specialist follow
      up. SEARCH STRATEGY: We searched the Cochrane Diabetes Group specialised
      register, The Cochrane Library, MEDLINE (January 1966 to December 1996), EMBASE
      (to December 1996), Cinahl (to December 1996), National Research Register (to
      December 1996), PsycLIT (to December 1996), HealthSTAR (to December 1996), CRIB
      (to December 1996), Dissertation Abstracts (to December 1996), and reference
      lists of articles. SELECTION CRITERIA: Randomised trials in which people with
      diabetes were allocated to a system of review and surveillance for complications
      by primary care professionals. Outcomes included mortality, metabolic control,
      cardiovascular risk factors, quality of life, functional status, satisfaction,
      hospital admissions, costs, completeness of screening, and development of
      complications. DATA COLLECTION AND ANALYSIS: The reviewer assessed trial quality
      and extracted data. Analysis was on an intention to treat basis. General practice
      care was categorised into routine or prompted care and a stratified analysis
      undertaken. MAIN RESULTS: Five trials involving 1058 people were included.
      Results were heterogeneous between trials. In those schemes featuring more
      intensive support through a prompting system for general practitioners and
      patients, there was no difference in mortality between hospital and general
      practice care (odds ratio 1.06, 95% confidence interval 0.53 to 2.11), HbA1
      tended to be lower (a weighted difference in means of -0.27%, 95% confidence
      interval -0.59 to 0.03) and losses to follow up were significantly lower (odds
      ratio 0.37, 95% confidence interval 0.22 to 0.61) in primary care. However,
      schemes with less well-developed support for family doctors were associated with
      adverse outcomes for patients. Quality of life, cardiovascular risk factors,
      functional status and the development of complications were infrequently
      assessed. AUTHORS' CONCLUSIONS: Unstructured care in the community is associated
      with poorer follow up, greater mortality and worse glycaemic control than
      hospital care. Computerised central recall, with prompting for patients and their
      family doctors, can achieve standards of care as good or better than hospital
      outpatient care, at least in the short term. The evidence supports provision of
      regular prompted recall and review of people with diabetes by willing general
      practitioners and demonstrates that this can be achieved, if suitable
      organisation is in place.

PMID- 19160183
TI  - Post-operative radiotherapy for ductal carcinoma in situ of the breast.
AB  - BACKGROUND: The addition of radiotherapy (RT) following breast conserving surgery
      (BCS) was first shown to reduce the risk of ipsilateral recurrence in the
      treatment of invasive breast cancer. Ductal carcinoma in situ (DCIS) is a pre
      invasive lesion. Recurrence of ipsilateral disease following BCS can be either
      DCIS or invasive breast cancer. Randomised controlled trials (RCTs) have shown
      that RT can reduce the risk of recurrence, but assessment of potential long-term
      complications from addition of RT following BSC for DCIS has not been reported
      for women participating in RCTs. OBJECTIVES: To summarise the data from RCTs
      testing the addition of RT to BCS for treatment of DCIS to determine the balance
      between the benefits and harms. SEARCH STRATEGY: We searched the Cochrane Breast
      Cancer Group Specialised Register (January 2008), Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 1), MEDLINE
      (February 2008), and EMBASE (February 2008). Reference lists of articles and
      handsearching of ASCO (2007), ESMO (2002 to 2007), and St Gallen (2005 to 2007)
      conferences were performed. SELECTION CRITERIA: RCTs of breast conserving surgery
      with and without radiotherapy in women at first diagnosis of pure ductal
      carcinoma in situ (no invasive disease present). DATA COLLECTION AND ANALYSIS:
      Two authors independently assessed each potentially eligible trial for inclusion
      and its quality. Two authors also independently extracted data from published
      Kaplan-Meier analysis (survival curves) and reported summary statistics. Data
      were extracted and pooled for four trials. Data for planned subgroups were
      extracted and pooled for analysis.There were insufficient data to pool for long
      term toxicity from radiotherapy. MAIN RESULTS: Four RCTs involving 3925 women
      were identified and included in this review. All were high quality with minimal
      risk of bias. Three trials compared the addition of RT to BCS. One trial was a
      two by two factorial design comparing the use of RT and tamoxifen, each
      separately or together, in which participants were randomised in at least one
      arm. Analysis confirmed a statistically significant benefit from the addition of
      radiotherapy on all ipsilateral breast events (hazards ratio (HR) 0.49; 95% CI
      0.41 to 0.59, P < 0.00001) and ipsilateral DCIS recurrence (HR 0.64; 95% CI 0.41
      to 1.01, P = 0.05). Pooled analysis for invasive recurrence did not reach
      statistical significance. All the subgroups analysed benefited from addition of
      radiotherapy. No significant long-term toxicity from radiotherapy was found. No
      information about short-term toxicity from radiotherapy or quality of life data
      were reported. AUTHORS' CONCLUSIONS: This review confirms the benefit of adding
      radiotherapy to breast conserving surgery for the treatment of all women
      diagnosed with DCIS. No long-term toxicity from use of radiotherapy was
      identified.

PMID- 19160184
TI  - Vaccines for preventing tick-borne encephalitis.
AB  - BACKGROUND: Tick-borne encephalitis (TBE) is a disease of the central nervous
      system caused by a tick-borne viral infection. TBE can lead to severe
      neurological syndromes such as meningitis, meningoencephalitis, and
      meningoencephalomyelitis, which can result in death. There is no treatment, and
      prevention with the vaccine is the only intervention currently available.
      OBJECTIVES: To evaluate vaccines for preventing TBE in terms of effectiveness and
      adverse effects. SEARCH STRATEGY: In June 2008, we searched the Cochrane
      Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library
      2008, Issue 2), MEDLINE, EMBASE, LILACS, and mRCT. We also checked reference
      lists of articles. SELECTION CRITERIA: Randomized and quasi-randomized controlled
      trials comparing TBE vaccines against placebo, control vaccines, no intervention,
      or a different dose or schedule of the intervention vaccine. DATA COLLECTION AND
      ANALYSIS: Two authors applied the inclusion criteria, extracted data, and
      assessed each trial's risk of bias. We could not combine the included trials in a
      meta-analysis because of differences in comparisons and outcomes. MAIN RESULTS:
      Eleven trials (corresponding to 10 papers) involving 8184 participants (6586
      adults and 1598 children) were included. Different versions of three types of TBE
      vaccines were tested (IPVE, FSME-IMMUN, and Encepur); out of which only three
      (Encepur children, Encepur Adults, and FSME-IMMUN "new") are currently licensed.
      No trials reported on cases of clinical TBE, but all reported on antibody titre
      (seroconversion). All the vaccines gave seroconversion rates of over 87%.
      Systemic and local adverse effects were common; none were severe or life
      threatening. AUTHORS' CONCLUSIONS: Tick-borne encephalitis vaccines appear to be
      highly immunogenic, but the relationship between seroconversion and clinical
      protection has not been established. Although adverse effects were commonly
      reported, none were serious or life threatening.

PMID- 19160185
TI  - Vitamin C supplementation for asthma.
AB  - BACKGROUND: Vitamin C is one of the key antioxidant vitamins which is abundant in
      the extracellular fluid lining the lung and low vitamin C intake has been
      associated with pulmonary dysfunction. OBJECTIVES: To evaluate the evidence for
      the efficacy of vitamin C in the treatment of asthma. SEARCH STRATEGY: The
      Cochrane Airways Review Group asthma register was searched and bibliographies of
      studies identified were also checked for further trials. This review has been
      updated by searches to August 2008. SELECTION CRITERIA: Only randomised
      controlled trials were eligible for inclusion. Studies were considered for
      inclusion if they dealt with the treatment of asthma using vitamin C
      supplementation. Two independent reviewers identified potentially relevant
      studies using pre-defined criteria and selected studies for inclusion. DATA
      COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers.
      Information on patients, methods, interventions, outcomes and results was
      extracted using standard forms. MAIN RESULTS: Nine studies met the review entry
      criteria, randomising a total of 330 participants. Study design varied and the
      reporting was generally poor. Five trials contributed numerical data to the
      review. They provided outcome data on lung function, symptom scores, IgE levels
      and inhaled steroid use. One small study showed a significant difference in %
      drop in FEV1 post-exercise. AUTHORS' CONCLUSIONS: At present, evidence from
      randomised-controlled trials is insufficient to recommend a specific role for
      vitamin C in the treatment of asthma. Further methodologically strong and large
      scale randomised controlled trials are needed in order to address the question of
      the effectiveness of vitamin C in children with asthma.

PMID- 19160186
TI  - Inhaled steroids for bronchiectasis.
AB  - BACKGROUND: Bronchiectasis is increasingly recognized as a major cause of
      respiratory morbidity especially in developing countries and in some ethnic
      populations of affluent countries. It is characterized by irreversible dilatation
      of airways, generally associated with chronic bacterial infection. Medical
      management largely aims to reduce morbidity by controlling the symptoms and by
      preventing the progression of bronchiectasis. OBJECTIVES: To evaluate the
      efficacy of inhaled corticosteroids (ICS) in children and adults with
      bronchiectasis (a) during stable bronchiectasis; and for reducing; (b) the
      severity and frequency of acute respiratory exacerbations and (c) long term
      pulmonary decline. SEARCH STRATEGY: The Cochrane Register of Controlled Trials
      (CENTRAL), the Cochrane Airways Group Specialized Register Collaboration and
      Cochrane Airways Group, MEDLINE and EMBASE databases were searched by the
      Cochrane Airways Group. The latest searches were performed in September 2007.
      SELECTION CRITERIA: All randomised controlled trials comparing ICS with a placebo
      or no medication. Children and adults with clinical or radiographic evidence of
      bronchiectasis were included, but patients with cystic fibrosis (CF) were
      excluded. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against
      pre-determined criteria for inclusion. MAIN RESULTS: There were no paediatric
      studies. Six adult studies fulfilled the inclusion criteria. Of the 303
      randomised, 278 subjects completed the trials. In the short term group (ICS for
      less then 6 months duration), adults on huge doses of ICS (2g per day of
      budesonide equivalent) had significantly improved forced expiratory volume in the
      first second (FEV(1)), forced vital capacity (FVC), Quality of life (QOL) score
      and sputum volume but no significant difference in peak flow, exacerbations,
      cough or wheeze, when compared to adults in the control arm (no ICS). When only
      placebo-controlled studies were included, there were no significant difference
      between groups in all outcomes examined (spirometry, clinical outcomes of
      exacerbation or sputum volume etc). The single study on long term outcomes showed
      no significant effect of inhaled steroids in any of the outcomes. AUTHORS'
      CONCLUSIONS: The present review indicates that there is insufficient evidence to
      recommend the routine use of inhaled steroids in adults with stable state
      bronchiectasis. While a therapeutic trial may be justified in adults with
      difficult to control symptoms and in certain subgroups, this has to be balanced
      with adverse events especially if high doses are used. No recommendation can be
      made for the use of ICS in adults during an acute exacerbation or in children
      (for any state) as there were no studies.

PMID- 19160187
TI  - Hypothermia for traumatic head injury.
AB  - BACKGROUND: Hypothermia has been used in the treatment of head injury for many
      years. Encouraging results from small trials and laboratory studies led to
      renewed interest in the area and some larger trials. OBJECTIVES: To estimate the
      effect of mild hypothermia for traumatic head injury on mortality and long-term
      functional outcome complications. SEARCH STRATEGY: We searched the Injuries Group
      Specialised Register, Current Controlled Trials MetaRegister of trials, Zetoc,
      Web of Knowledge; Science Citation Index [expanded], CENTRAL, MEDLINE and EMBASE.
      We handsearched conference proceedings and checked reference lists of relevant
      articles. The search was updated on 23 May 2008. SELECTION CRITERIA: Randomised
      controlled trials of hypothermia to a maximum of 35 degrees C for at least 12
      hours versus control in patients with any closed traumatic head injury requiring
      hospitalisation. Two authors independently assessed all trials. DATA COLLECTION
      AND ANALYSIS: Data on death, Glasgow Outcome Scale and pneumonia were sought and
      extracted, either from published material or by contacting the investigators.
      Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each
      trial on an intention-to-treat basis. MAIN RESULTS: We found 22 trials with a
      total of 1409 randomised patients. Twenty trials involving 1382 patients reported
      deaths. There were fewer deaths in patients treated with hypothermia than in the
      control group (OR 0.76, 95% CI 0.60 to 0.97). Eight trials with good allocation
      concealment showed a non-significant reduction in the likelihood of death for
      patients treated with hypothermia (OR 0.96, 95% CI 0.68 to 1.35). Twenty trials
      involving 1382 patients reported data on unfavourable outcomes (death, vegetative
      state or severe disability). Patients treated with hypothermia were less likely
      to have an unfavourable outcome than those in the control group (OR 0.69, 95% CI
      0.55 to 0.86). Eight trials with good allocation concealment showed a non
      significant reduction in the likelihood of unfavourable outcome for patients
      treated with hypothermia (OR 0.79, 95% CI 0.57 to 1.08). Hypothermia treatment
      was associated with an increase in odds of pneumonia but this increase was not
      statistically significant for trials with good allocation concealment (3 trials,
      69 patients, OR 1.06, 95% CI 0.38 to 2.97). AUTHORS' CONCLUSIONS: Hypothermia may
      be effective in reducing death and unfavourable outcomes for traumatic head
      injured patients, but significant benefit was only found in low quality trials.
      Low quality trials have a tendency to overestimate the treatment effect. The high
      quality trials found some statistically non-significant benefit of hypothermia
      which could be due to the play of chance. Hypothermia may increase the risk of
      pneumonia. Due to uncertainties in its effects, hypothermia should only be given
      to patients taking part in a randomised controlled trial with good allocation
      concealment.

PMID- 19160188
TI  - Restricted versus liberal oxygen exposure for preventing morbidity and mortality
      in preterm or low birth weight infants.
AB  - BACKGROUND: While the use of supplemental oxygen has a long history in neonatal
      care, resulting in both significant health care benefits and harms, uncertainty
      remains as to the most appropriate range to target blood oxygen levels in preterm
      and low birth weight infants. Potential benefits of higher oxygen targeting may
      include more stable sleep patterns and improved long-term growth and development.
      However, there may be significant deleterious pulmonary effects and health
      service use implications resulting from such a policy. OBJECTIVES: To determine
      whether targeting ambient oxygen concentration to achieve a lower vs. higher
      blood oxygen range, or administering restricted vs. liberal supplemental oxygen,
      effects mortality, retinopathy of prematurity, lung function, growth or
      development in preterm or low birth weight infants. SEARCH STRATEGY: The standard
      search strategy of the Neonatal Review Group was used. An additional literature
      search was conducted of the MEDLINE and CINAHL databases in order to locate any
      trials in addition to those provided by the Cochrane Controlled Trials Register
      (CENTRAL/CCTR). Search updated to week two July 2008. SELECTION CRITERIA: All
      trials in preterm or low birth weight infants utilising random or quasi-random
      patient allocation in which ambient oxygen concentrations were targeted to
      achieve a lower vs. higher blood oxygen range, or restricted vs. liberal oxygen
      was administered were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The
      methodological quality of the eligible trials was assessed independently by each
      review author for the degree of selection, performance, attrition and detection
      bias. Data were extracted and reviewed independently by the each author. Data
      analysis was conducted according to the standards of the Cochrane Neonatal Review
      Group. MAIN RESULTS: In the meta-analysis of the five trials included in this
      review, the restriction of oxygen significantly reduced the incidence and
      severity of retinopathy of prematurity without unduly increasing death rates The
      one prospective, multicenter, double-blind, randomized trial investigating lower
      vs. higher blood oxygen levels from 32 weeks postmenstrual age showed no
      significant differences in the rates of ROP, mortality or growth and development
      between the two groups. However, this study did show increased rates of chronic
      lung disease and home oxygen use. AUTHORS' CONCLUSIONS: The results of this
      systematic review confirm that (the now historical) policy of unrestricted,
      unmonitored oxygen therapy has potential harms without clear benefits. However,
      the question of what is the optimal target range for maintaining blood oxygen
      levels in preterm/LBW infants was not answered by the data available for
      inclusion in this review.

PMID- 19160189
TI  - Late (>7 days) postnatal corticosteroids for chronic lung disease in preterm
      infants.
AB  - BACKGROUND: Many preterm infants who survive go on to develop chronic lung
      disease (CLD). This is true in infants who have had respiratory distress syndrome
      (RDS) and in infants without RDS. This is probably due to persistence of
      inflammation in the lung. Corticosteroids have powerful anti-inflammatory effects
      and have been used to treat established CLD. However, it is unclear whether any
      beneficial effects outweigh the adverse effects of these drugs. OBJECTIVES: To
      determine the effect of late (> 7 days) postnatal corticosteroid treatment
      compared to control (placebo or nothing) in the preterm infant with CLD. SEARCH
      STRATEGY: Randomised controlled trials of postnatal corticosteroid therapy were
      sought from the Cochrane Central Register of Controlled Trials (The Cochrane
      Library), MEDLINE 1966 through May 2008, hand searching paediatric and perinatal
      journals, examining previous review articles and information received from
      practising neonatologists. When possible, authors of all studies were contacted
      to confirm details of reported follow-up studies or to obtain any information
      about long-term follow-up where none had been reported. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) of postnatal corticosteroid treatment
      initiated after seven days after birth in preterm infants with or developing CLD
      were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding
      clinical outcomes including mortality, CLD (including need for home oxygen, or
      need for late rescue with corticosteroids), death or CLD, failure to extubate,
      complications in the primary hospitalisation (including infection,
      hyperglycaemia, glycosuria, hypertension, echodensities on ultrasound scan of
      brain, necrotising enterocolitis (NEC), gastrointestinal (GI) bleeding, GI
      perforation, intraventricular hemorrhage (IVH), severe retinopathy of prematurity
      (ROP), and long-term outcomes (including blindness, deafness, cerebral palsy and
      major neurosensory disability), were abstracted and analysed using RevMan 5 MAIN
      RESULTS: Nineteen RCTs enrolling a total of 1345 participants were eligible for
      this review. Late steroid treatment was associated with a reduction in neonatal
      mortality (at 28 days) but not mortality at discharge or latest reported age.
      Beneficial effects of delayed steroid treatment included reductions in failure to
      extubate by 3, 7 or 28 days, CLD at both 28 days and 36 weeks' postmenstrual age
      (overall and in survivors), need for late rescue treatment with dexamethasone,
      discharge to home on oxygen therapy, and death or CLD at both 28 days and 36
      weeks' postmenstrual age (PMA). There was a trend towards an increase in risk of
      infection and GI bleeding but not NEC. Short-term adverse affects included
      hyperglycaemia, glycosuria and hypertension. There was an increase in severe ROP
      (overall and a trend in survivors) but no significant increase in blindness.
      There was trend towards a reduction in severe IVH but only 247 infants were
      enrolled in five studies reporting this outcome. The trends to an increase in
      cerebral palsy or abnormal neurological examination were partly offset by a trend
      in the opposite direction in death before late follow-up. The combined rate of
      death or cerebral palsy was not significantly different between steroid and
      control groups. Major neurosensory disability, and the combined rate of death or
      major neurosensory disability, were not significantly different between steroid
      and control groups. There were no substantial differences between groups for
      other outcomes in later childhood, including respiratory health or function,
      blood pressure, or growth. AUTHORS' CONCLUSIONS: The benefits of late
      corticosteroid therapy may not outweigh actual or potential adverse effects.
      Although there continues to be concern about an increased incidence of adverse
      neurological outcomes in infants treated with postnatal steroids (see also review
      of "Early postnatal corticosteroids for preventing chronic lung disease in
      preterm infants"), this review of postnatal corticosteroid treatment for CLD
      initiated after seven days of age suggests that late therapy may reduce neonatal
      mortality without significantly increasing the risk of adverse long-term
      neurodevelopmental outcomes. However, the methodological quality of the studies
      determining the long-term outcome is limited in some cases; in some studies the
      surviving children have only been assessed before school age when some important
      neurological outcomes cannot be determined with certainty, and no study was
      sufficiently powered to detect increased rates of important adverse long-term
      neurosensory outcomes. Given the evidence of both benefits and harms of
      treatment, and the limitations of the evidence at present, it appears prudent to
      reserve the use of late corticosteroids to infants who cannot be weaned from
      mechanical ventilation and to minimise the dose and duration of any course of
      treatment.

PMID- 19160190
TI  - Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in
      preterm infants.
AB  - BACKGROUND: Chronic lung disease (CLD) remains a major problem in neonatal
      intensive care units. Persistent inflammation in the lungs is the most likely
      underlying pathogenesis. Corticosteroids have been used to either prevent or
      treat CLD because of their potent anti-inflammatory effects. OBJECTIVES: To
      determine if postnatal corticosteroid treatment is of benefit in the prevention
      of chronic lung disease (CLD) in preterm infants. This review examines the
      outcome of trials where preterm infants at risk of CLD were given postnatal
      corticosteroids within the first seven days of life. SEARCH STRATEGY: Randomised
      controlled trials (RCTs) of postnatal corticosteroid therapy were sought from the
      Cochrane Controlled Trials Register, MEDLINE (1966 - May 2008), hand searching
      paediatric and perinatal journals, examining previous review articles and
      information received from practising neonatologists. Authors of all studies were
      contacted, where possible, to confirm details of reported follow-up studies, or
      to obtain any information about long-term follow-up where none had been reported.
      SELECTION CRITERIA: Randomised controlled trials of postnatal corticosteroid
      treatment within the first 7 days of life (early) in high risk preterm infants
      were selected for this review. Most studies evaluated the use of dexamethasone
      but we also included studies that assessed hydrocortisone, even if it was used to
      manage hypotension. DATA COLLECTION AND ANALYSIS: Data regarding clinical
      outcomes including mortality, CLD (including late rescue with corticosteroids,
      and need for home oxygen therapy), death or CLD, failure to extubate,
      complications during the primary hospitalisation (including infection,
      hyperglycaemia, hypertension, pulmonary air leak, patent ductus arteriosus (PDA),
      severe intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL),
      necrotising enterocolitis (NEC), gastrointestinal bleeding, intestinal
      perforation, severe retinopathy of prematurity (ROP), and long-term outcome
      (including blindness, deafness, cerebral palsy and major neurosensory disability)
      were abstracted and analysed using RevMan 5. MAIN RESULTS: Twenty-eight RCTs
      enrolling a total of 3740 participants were eligible for inclusion in this
      review. A meta-analysis of these trials demonstrated significant benefits as
      regards earlier extubation and decreased risks of CLD at both 28 days and 36
      weeks' postmenstrual age (PMA), death or CLD at 28 days and 36 weeks' PMA, PDA
      and ROP, including severe ROP. There were no significant differences in the rates
      of neonatal or subsequent mortality, infection, severe IVH, PVL, NEC or pulmonary
      haemorrhage. Gastrointestinal bleeding and intestinal perforation were important
      adverse effects and the risks of hyperglycaemia, hypertension, hypertrophic
      cardiomyopathy and growth failure were also increased. In the twelve trials that
      reported late outcomes, several adverse neurological effects were found at follow
      up examinations including developmental delay (not defined), cerebral palsy and
      abnormal neurological examination. However, major neurosensory disability was not
      significantly increased, either overall in the seven studies where this outcome
      could be determined, or in the two individual studies where the rates of cerebral
      palsy or abnormal neurological examination were significantly increased.
      Moreover, the rates of the combined outcomes of death or cerebral palsy, or of
      death or major neurosensory disability were not significantly increased.
      Dexamethasone was the drug used in most studies (n = 20); only eight studies used
      hydrocortisone. In subgroup analyses by type of corticosteroid, most of the
      beneficial and harmful effects were attributable to dexamethasone; hydrocortisone
      had little effect on any outcomes except for an increase in intestinal
      perforation and a borderline reduction in PDA. AUTHORS' CONCLUSIONS: The benefits
      of early postnatal corticosteroid treatment (</= 7 days), particularly
      dexamethasone, may not outweigh the known or potential adverse effects of this
      treatment. Although early corticosteroid treatment facilitates extubation and
      reduces the risk of chronic lung disease and patent ductus arteriosus, it causes
      short-term adverse effects including gastrointestinal bleeding, intestinal
      perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth
      failure. Long-term follow-up studies report an increased risk of abnormal
      neurological examination and cerebral palsy. However, the methodological quality
      of the studies determining long-term outcomes is limited in some cases; the
      surviving children have been assessed predominantly before school age, and no
      study has been sufficiently powered to detect important adverse long-term
      neurosensory outcomes. There is a compelling need for the long-term follow-up and
      reporting of late outcomes, especially neurological and developmental outcomes,
      among surviving infants who participated in all randomised trials of early
      postnatal corticosteroid treatment. Hydrocortisone in the doses and regimens used
      in the reported RCTs has few beneficial or harmful effects and cannot be
      recommended for prevention of CLD.

PMID- 19160191
TI  - Antimicrobial prophylaxis for colorectal surgery.
AB  - BACKGROUND: Research shows that administration of prophylactic antibiotics before
      colorectal surgery prevents postoperative surgical wound infection (SWI). The
      best antibiotic choice, timing of administration and route of administration
      remain undetermined. OBJECTIVES: To establish the effectiveness of antimicrobial
      prophylaxis for the prevention of SWI in patients undergoing colorectal surgery:
      specifically to determine, 1 Whether it reduces risk of SWI. 2 The target
      spectrum/a of bacteria (aerobic and/or anaerobic). 3 The best timing and duration
      of antibiotic administration. 4 The most effective route of antibiotic
      administration (intravenous, oral or both). 5 Whether any antibiotic is clearly
      more effective than the currently recommended gold standard. SEARCH STRATEGY:
      CENTRAL, MEDLINE, and EMBASE, were searched from January, 1980 to December, 2007.
      SELECTION CRITERIA: Randomised controlled trials of prophylactic antibiotic use
      in elective and emergency colorectal surgery, with SWI as an outcome. DATA
      COLLECTION AND ANALYSIS: Data were abstracted and reviewed by three authors for
      only the single, dichotomous outcome of SWI. MAIN RESULTS: The review included
      182 trials (30,880 participants), and 50 different antibiotics, including 17
      cephalosporins. Many studies had multiple variables that separated the two study
      groups and could not be compared to other studies that tested one antibiotic and
      had a single variable separating the two groups. Meta-analyses demonstrated a
      statistically significant difference in postoperative SWI when prophylactic
      antibiotics were compared to placebo/no treatment (relative risk (RR) 0.30, 95%
      confidence intervals (CI) 0.22 to 0.41). No statistically significant differences
      were shown when comparing short- and long-term duration of prophylaxis (RR 1.06,
      95% CI 0.89 to 1.27); or single dose versus multiple dose antibiotics (RR 1.17,
      95% CI 0.67 to 2.05). Additional aerobic coverage and additional anaerobic
      coverage both showed statistically significant improvements in SWI rates (RR
      0.41, 95% CI 0.23 to 0.71 and RR 0.55, 95% CI 0.35 to 0.85, respectively); as did
      combined oral and intravenous antibiotic prophylaxis when compared to intravenous
      alone (RR 0.55, 95% CI 0.41 to 0.74), or oral alone (RR 0.34, 95% CI 0.13 to
      0.87). Established gold standard regimens were no less effective than any other
      antibiotic choice. AUTHORS' CONCLUSIONS: Antibiotics covering aerobic and aerobic
      bacteria should be delivered orally and intravenously prior to colorectal
      surgery. Antibiotics delivered within this framework will reduce the risk of
      postoperative SWI by at least 75%. Further research is required to establish the
      optimal timing and duration of dosing, and frequency of longer-term adverse
      effects such as Clostridium difficile pseudomembranous colitis.

PMID- 19160192
TI  - Neoadjuvant and adjuvant therapy for surgical resection of hepatocellular
      carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma is a disease of great concern. Surgery is
      the treatment of choice, but there is still a high recurrence rate after
      resection. OBJECTIVES: To determine the benefits and harms of neoadjuvant and
      adjuvant therapies compared to surgery alone or surgery and placebo/supportive
      therapy after curative resection for operable hepatocellular carcinoma. SEARCH
      STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The
      Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, Chinese
      Biomedical Database, and US National Cancer Institute's Physician's Data Query
      Trials Database until 2005. References of the identified trials were also
      searched for identifying further trials. SELECTION CRITERIA: Randomised and quasi
      randomised trials that compared hepatocellular carcinoma patients who were given
      and not given neoadjuvant/adjuvant therapy as a supplement to curative liver
      resection. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two
      authors and discrepancies resolved by consensus. The survival and disease-free
      survival curves were compared using their one, two, three, four, and five-year
      survival rates, median survival times, and the result of the significance tests
      (P-values). MAIN RESULTS: A total of 12 randomised trials were identified,
      totaling 843 patients. The size of the randomised clinical trials ranged from 30
      to 155 patients. Both preoperative (neoadjuvant) and postoperative (adjuvant),
      systemic and locoregional (+/- embolisation), chemo- and immunotherapy
      interventions were tested. Treatment regimens and patients selected were not
      comparable, so no pooling was done. Only one regimen using preoperative
      transcatheter arterial chemoembolisation with doxorubicin was similar in two
      trials. Four of the twelve trials reported survival benefit at five years when
      given adjuvant or neoadjuvant therapy. Disease-free survival was reported in nine
      trials, and the estimated hazard ratios show that disease-free survival was
      significant in two trials at five years. These two trials had not shown a
      survival advantage, but the recurrence was significantly lower in patients given
      adjuvant or neoadjuvant therapy. The highest toxicity rate was in a trial using
      oral 1-hexylcarbamoyl 5-fluorouracil which resulted in 12 out of 38 patients
      being withdrawn from the trial because of adverse events. AUTHORS' CONCLUSIONS:
      There is no clear evidence for efficacy of any of the adjuvant and neo-adjuvant
      protocols reviewed, but there is some evidence to suggest that adjuvant therapy
      may be beneficial offering prolonged disease-free survival. In order to detect a
      realistic treatment advantage, larger trials with lower risk of systematic error
      will have to be conducted.

PMID- 19160193
TI  - Acupuncture for migraine prophylaxis.
AB  - BACKGROUND: Acupuncture is often used for migraine prophylaxis but its
      effectiveness is still controversial. This review (along with a companion review
      on 'Acupuncture for tension-type headache') represents an updated version of a
      Cochrane review originally published in Issue 1, 2001, of The Cochrane Library.
      OBJECTIVES: To investigate whether acupuncture is a) more effective than no
      prophylactic treatment/routine care only; b) more effective than 'sham' (placebo)
      acupuncture; and c) as effective as other interventions in reducing headache
      frequency in patients with migraine. SEARCH STRATEGY: The Cochrane Pain,
      Palliative & Supportive Care Trials Register, CENTRAL, MEDLINE, EMBASE and the
      Cochrane Complementary Medicine Field Trials Register were searched to January
      2008. SELECTION CRITERIA: We included randomized trials with a post-randomization
      observation period of at least 8 weeks that compared the clinical effects of an
      acupuncture intervention with a control (no prophylactic treatment or routine
      care only), a sham acupuncture intervention or another intervention in patients
      with migraine. DATA COLLECTION AND ANALYSIS: Two reviewers checked eligibility;
      extracted information on patients, interventions, methods and results; and
      assessed risk of bias and quality of the acupuncture intervention. Outcomes
      extracted included response (outcome of primary interest), migraine attacks,
      migraine days, headache days and analgesic use. Pooled effect size estimates were
      calculated using a random-effects model. MAIN RESULTS: Twenty-two trials with
      4419 participants (mean 201, median 42, range 27 to 1715) met the inclusion
      criteria. Six trials (including two large trials with 401 and 1715 patients)
      compared acupuncture to no prophylactic treatment or routine care only. After 3
      to 4 months patients receiving acupuncture had higher response rates and fewer
      headaches. The only study with long-term follow up saw no evidence that effects
      dissipated up to 9 months after cessation of treatment. Fourteen trials compared
      a 'true' acupuncture intervention with a variety of sham interventions. Pooled
      analyses did not show a statistically significant superiority for true
      acupuncture for any outcome in any of the time windows, but the results of single
      trials varied considerably. Four trials compared acupuncture to proven
      prophylactic drug treatment. Overall in these trials acupuncture was associated
      with slightly better outcomes and fewer adverse effects than prophylactic drug
      treatment. Two small low-quality trials comparing acupuncture with relaxation
      (alone or in combination with massage) could not be interpreted reliably.
      AUTHORS' CONCLUSIONS: In the previous version of this review, evidence in support
      of acupuncture for migraine prophylaxis was considered promising but
      insufficient. Now, with 12 additional trials, there is consistent evidence that
      acupuncture provides additional benefit to treatment of acute migraine attacks
      only or to routine care. There is no evidence for an effect of 'true' acupuncture
      over sham interventions, though this is difficult to interpret, as exact point
      location could be of limited importance. Available studies suggest that
      acupuncture is at least as effective as, or possibly more effective than,
      prophylactic drug treatment, and has fewer adverse effects. Acupuncture should be
      considered a treatment option for patients willing to undergo this treatment.

PMID- 19160195
TI  - Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: COPD is a common condition, mainly related to smoking. Acute
      exacerbations of COPD, usually related to superimposed infection, occur commonly
      and systemic corticosteroids are widely used in their management in combination
      with other treatments including antibiotics, oxygen supplementation and
      bronchodilators. OBJECTIVES: To determine the efficacy of corticosteroids,
      administered either parenterally or orally, on the outcomes of acute
      exacerbations of COPD. SEARCH STRATEGY: Searches were carried out using the
      Cochrane Airways Group COPD RCT register with additional studies sought in the
      bibliographies of randomised controlled trials and review articles. Authors of
      identified randomised controlled trials were contacted for other published and
      unpublished studies. The last search was carried out in August 2008. SELECTION
      CRITERIA: Randomised controlled trials comparing corticosteroids, administered
      either parenterally or orally, with appropriate placebo control. Other
      interventions e.g. bronchodilators and antibiotics were standardised. Clinical
      studies of acute asthma were excluded. DATA COLLECTION AND ANALYSIS: Data were
      extracted independently by two reviewers. Data measured but not reported were
      sought from authors of included studies. Trials were combined using Review
      Manager for analyses. MAIN RESULTS: Eleven studies (n=1081) fulfilled the
      inclusion criteria and 10 studies contributed data for analyses (n=1051). There
      were significantly fewer treatment failures within thirty days in patients given
      corticosteroid treatment, Odds Ratio (OR) 0.50; 95% confidence interval (CI) 0.36
      to 0.69 and Hazard Ratio 0.78; 95% CI 0.63 to 0.97. It would have been necessary
      to treat 10 patients (95%CI 7 to 16) with corticosteroids to avoid one treatment
      failure in this time period. Duration of hospitalisation was significantly
      shorter with corticosteroid treatment, mean difference -1.22 days; 95% CI -2.26
      to -0.18. For FEV1 there were significant treatment benefits with mean
      differences at the early time point (to 72 hours), 140 ml; 95% CI 90 to 190 ml
      and at end of treatment (up to 15 days) 80 ml; 95% confidence interval 10 to 160.
      There was a significant improvement in breathlessness and blood gases at both
      time points. There was no significant effect on mortality but an increased
      likelihood of an adverse event associated with corticosteroid treatment, OR 2.33;
      95% CI 1.60 to 3.40. Overall one extra adverse effect occurred for every 5 people
      treated (95% CI 4 to 9). The risk of hyperglycaemia was significantly increased,
      OR 4.95; 95% CI 2.47 to 9.91. AUTHORS' CONCLUSIONS: Treatment of an exacerbation
      of COPD with oral or parenteral corticosteroids significantly reduces treatment
      failure and the need for additional medical treatment and shortens hospital stay.
      It increases the rate of improvement in lung function and dyspnoea and the
      improvement continues during treatment, but there is a significantly increase in
      the risk of an adverse drug event occurring. The optimal dose and length of
      treatment regime needs to be better defined.

PMID- 19160194
TI  - Cooling therapy for acute stroke.
AB  - BACKGROUND: Increased body temperatures are common in patients with acute stroke
      and are associated with poor outcome. In animal models of focal cerebral
      ischaemia, temperature-lowering therapy reduces infarct volume. In patients with
      acute stroke, lowering temperature may therefore improve outcome. This is an
      update of a Cochrane review first published in 1999. OBJECTIVES: To assess the
      effects of pharmacological and physical strategies to reduce body or brain
      temperature in patients with acute stroke. SEARCH STRATEGY: We searched the
      Cochrane Stroke Group trials register (last searched December 2007). In addition,
      we searched MEDLINE and EMBASE (January 1998 to December 2007). We scanned
      references and contacted authors of included trials. For the previous version of
      this review, the authors contacted pharmaceutical companies and manufactures of
      cooling equipment in this field. SELECTION CRITERIA: We considered all completed
      randomised or non-randomised controlled clinical trials, published or
      unpublished, where pharmacological or physical strategies or both to reduce
      temperature were applied in patients with acute ischaemic stroke or intracerebral
      haemorrhage. Outcome measures were death or dependency (modified Rankin Scale
      score >/= 3) at the end of follow up, and adverse effects. DATA COLLECTION AND
      ANALYSIS: Two review authors independently applied the inclusion criteria,
      assessed trial quality, and extracted and cross-checked the data. MAIN RESULTS:
      We included five pharmacological temperature reduction trials and three physical
      cooling trials involving a total of 423 participants. We found no statistically
      significant effect of pharmacological or physical temperature-lowering therapy in
      reducing the risk of death or dependency (odds ratio (OR) 0.9, 95% confidence
      interval (CI) 0.6 to 1.4) or death (OR 0.9, 95% CI 0.5 to 1.5). Both
      interventions were associated with a non-significant increase in the occurrence
      of infections. AUTHORS' CONCLUSIONS: There is currently no evidence from
      randomised trials to support routine use of physical or pharmacological
      strategies to reduce temperature in patients with acute stroke. Large randomised
      clinical trials are needed to study the effect of such strategies.

PMID- 19160196
TI  - WITHDRAWN: Surgical treatment for meniscal injuries of the knee in adults.
AB  - BACKGROUND: Injuries to the knee menisci are common and operations to treat them
      are among the most common procedures performed by orthopaedic surgeons.
      OBJECTIVES: To evaluate the effects of common surgical interventions in the
      treatment of meniscal injuries of the knee. The four comparisons under test were:
      a) surgery versus conservative treatment, b) partial versus total meniscectomy,
      c) excision versus repair of meniscal tears, d) surgical access, in particular
      arthroscopic versus open. SEARCH STRATEGY: We searched the Cochrane Bone, Joint
      and Muscle Trauma Group specialised register (March 2001), MEDLINE (1966 -1998)
      and bibliographies of published papers. SELECTION CRITERIA: All randomised and
      quasi-randomised trials which involved the above four comparisons or which
      compared other surgical interventions for the treatment of meniscal injury. DATA
      COLLECTION AND ANALYSIS: Trial inclusion was agreed by both reviewers who
      independently assessed trial quality, by use of a 12 item scale, and extracted
      data. Where possible and appropriate, data were presented graphically. MAIN
      RESULTS: Three trials, involving 260 patients, which addressed two (partial
      versus total meniscectomy; surgical access) comparisons were included.Partial
      meniscectomy may allow a slightly enhanced recovery rate as well as a potentially
      improved overall functional outcome including better knee stability in the long
      term. It is probably associated with a shorter operating time with no apparent
      difference in early complications or re-operation between partial and total
      meniscectomy. The long term advantage of partial meniscectomy indicated by the
      absence of symptoms (symptoms or further operation at six years or over: 14/98
      versus 22/94; Peto odds ratio 0.55, 95% confidence interval 0.27 to 1.14) or
      radiographical outcome was not established.The results available from the only
      trial comparing arthroscopic with open meniscectomy were very limited in terms of
      patient numbers and length of follow-up. However it is likely that partial
      meniscectomy via arthroscopy is associated with shorter operating times and a
      quicker recovery. AUTHORS' CONCLUSIONS: The lack of randomised trials means that
      no conclusions can be drawn on the issue of surgical versus non-surgical
      treatment of meniscal injuries, nor meniscal tear repair versus excision.In
      randomised trials so far reported, there is no evidence of difference in
      radiological or long term clinical outcomes between arthroscopic and open
      meniscal surgery, or between total and partial meniscectomy. Partial meniscectomy
      seems preferable to the total removal of the meniscus in terms of recovery and
      overall functional outcome in the short term.

PMID- 19160197
TI  - Newborn screening for cystic fibrosis.
AB  - BACKGROUND: Does newborn screening for cystic fibrosis (CF) improve clinical
      outcomes, quality of life and survival? OBJECTIVES: To examine whether newborn
      screening for CF prevents or reduces irreversible organ damage and improves
      clinical outcomes, quality of life and survival in people with CF without
      unacceptable adverse effects. SEARCH STRATEGY: We searched the Cochrane Cystic
      Fibrosis and Genetic Disorders Group Trials Register comprising references
      identified from electronic database searches, handsearches of relevant journals
      and abstract books of conference proceedings.The Group's Trials Register last
      searched: June 2008. SELECTION CRITERIA: Randomised or quasi-randomised
      controlled trials, published and unpublished, comparing screening to clinical
      diagnosis in people with CF. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trial eligibility and quality and independently extracted
      data. Allocation concealment was unclear in both studies and sequence generation
      adequate in one. MAIN RESULTS: Searches identified six trials. Two trials
      involving 1,124,483 neonates (210 with CF) with a maximum follow up of 17 years
      were eligible for inclusion. Varying study designs, outcomes reported and summary
      measures precluded calculation of pooled estimates and only data from one study
      were analysed. Severe malnutrition was less common among screened participants.
      Compared with screened participants, the odds ratio of weight below the tenth
      percentile was 4.12 (95% CI 1.64 to 10.38) and for height was 4.62 (95% CI 1.69
      to 12.61) in the control group.At age seven, 88% of screened participants and 75%
      of controls had lung function parameters within normal limits of at least 89%
      predicted. At diagnosis chest radiograph scores were significantly better among
      screened participants; 33% of screened versus 50% of control participants had
      Wisconsin chest X-ray (WCXR) scores over five (P = 0.097) and 24% of screened
      versus 45% of control participants had Brasfield chest X-ray (BCXR) scores under
      21 (P = 0.042)). Over time, chest radiograph scores were worse in the screened
      group (WCXR P = 0.017 and BCXR P = 0.041). Results were no longer significant
      after adjustment for genotype, pancreatic status, and Pseudomonas aeruginosa
      culture results. In screened participants colonisation with Pseudomonas
      aeruginosa occurred earlier. Estimates suggest diagnosis through screening is
      less expensive. AUTHORS' CONCLUSIONS: Two randomised controlled trials assessing
      neonatal screening in CF were identified; data from one study were included.
      Nutritional benefits are apparent. Screening provides potential for better
      pulmonary outcomes, but confounding factors influenced long-term pulmonary
      prognosis of people with CF. Screening seems less expensive than traditional
      diagnosis.

PMID- 19160198
TI  - Mechanical bowel preparation for elective colorectal surgery.
AB  - BACKGROUND: The presence of bowel contents during surgery has been related to
      anastomotic leakage, but the belief that mechanical bowel preparation (MBP) is an
      efficient agent against leakage and infectious complications is based on
      observational data and expert opinions only. OBJECTIVES: To determine the
      security and effectiveness of MBP on morbidity and mortality in colorectal
      surgery. SEARCH STRATEGY: Publications describing trials of MBP before elective
      colorectal surgery were sought through searches of MEDLINE, EMBASE, LILACS, and
      The Cochrane Library; by handsearching relevant medical journals and conference
      proceedings, and through personal communication with colleagues.Searches were
      performed March 13, 2008. SELECTION CRITERIA: Randomised controlled trials (RCTs)
      including participants submitted for elective colorectal surgery. Eligible
      interventions included any type of MBP compared with no MBP. Primary outcomes
      included anastomosis leakage - both rectal and colonic - and combined figures.
      Secondary outcomes included mortality, peritonitis, reoperation, wound infection,
      extra-abdominal complications, and overall surgical site infections. DATA
      COLLECTION AND ANALYSIS: Data were independently extracted and checked. The
      methodological quality of each trial was assessed. Details of randomisation,
      blinding, type of analysis, and number lost to follow up were recorded. For
      analysis, the Peto-Odds Ratio (OR) was used as the default (no statistical
      heterogeneity was observed). MAIN RESULTS: Four new trials were included at this
      update (total 13 RCTs with 4777 participants; 2390 allocated to MBP (Group A),
      and 2387 to no preparation (Group B), before elective colorectal surgery)
      .Anastomotic leakage occurred:(i) in 10.0% (14/139) of Group A, compared with
      6.6% (9/136) of Group B for low anterior resection; Peto OR 1.73 (95% confidence
      interval (CI): 0.73 to 4.10).(ii) in 2.9% (32/1226) of Group A, compared with
      2.5% (31/1228) of Group B for colonic surgery; Peto OR 1.13 (95% CI: 0.69 to
      1.85). Overall anastomotic leakage occurred in 4.2% (102/2398) of Group A,
      compared with 3.4% (82/2378) of Group B; Peto OR 1.26 (95% CI: 0.941 to 1.69).
      Wound infection occurred in 9.6% (232/2417) of Group A, compared with 8.3%
      (200/2404) of Group B; Peto OR 1.19 (95% CI: 0.98 to 1.45). Sensitivity analyses
      did not produce any differences in overall results. AUTHORS' CONCLUSIONS: There
      is no statistically significant evidence that patients benefit from MBP. The
      belief that MBP is necessary before elective colorectal surgery should be
      reconsidered. Further research on patients submitted for elective colorectal
      surgery in whom bowel continuity is restored, with stratification for colonic and
      rectal surgery, is still warranted.

PMID- 19160200
TI  - Intravenous immunoglobulin for chronic inflammatory demyelinating
      polyradiculoneuropathy.
AB  - BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
      causes progressive or relapsing weakness and numbness of the limbs, developing
      over at least two months. Uncontrolled studies suggest that intravenous
      immunoglobulin (IVIg) helps. OBJECTIVES: To review systematically the evidence
      from randomised controlled trials concerning the efficacy and safety of IVIg in
      CIDP. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Trials Register,
      MEDLINE, EMBASE and ISI from January 1985 to May 2008. SELECTION CRITERIA:
      Randomised controlled studies testing any dose of IVIg versus placebo, plasma
      exchange or corticosteroids in definite or probable CIDP. DATA COLLECTION AND
      ANALYSIS: Two authors reviewed literature searches to identify potentially
      relevant trials, scored their quality and extracted data independently. We
      contacted authors for additional information. MAIN RESULTS: Seven randomised
      controlled trials were considered eligible including 287 participants. These
      trials were homogeneous and overall quality was high. Five studies on 235
      participants compared IVIg against placebo. One trial with 20 participants
      compared IVIg with plasma exchange and one trial compared IVIg with prednisolone
      in 32 participants. A significantly higher proportion of participants improved in
      disability within one month after IVIg treatment as compared with placebo
      (relative risk 2.40, 95% confidence interval 1.72 to 3.36). Whether all these
      improvements are equally clinically relevant cannot be deduced from this analysis
      because each trial used different disability scales and definitions of
      significant improvement. In three trials including 84 participants the disability
      could be transformed to the modified Rankin score, on which significantly more
      patients improved one point after IVIg treatment compared to placebo (relative
      risk 2.40, 95% confidence interval 0.98 to 5.83). Only one study included in this
      review had a long-term follow-up. The results of this study suggest that
      intravenous immunoglobulin improves disability more than placebo over 24 and 48
      weeks. The mean disability score revealed no significant difference between IVIg
      and plasma exchange at six weeks. There was no significant difference in
      improvement in disability on prednisolone compared with IVIg after two or six
      weeks. There were no statistically significant differences in frequencies of side
      effects between the three types of treatment. AUTHORS' CONCLUSIONS: The evidence
      from randomised controlled trials shows that intravenous immunoglobulin improves
      disability for at least two to six weeks compared with placebo, with a number
      needed to treat of 3.00. During this period it has similar efficacy to plasma
      exchange and oral prednisolone. In one large trial, benefit of IVIg persisted for
      24 and possibly 48 weeks.

PMID- 19160199
TI  - Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain
      in adults.
AB  - BACKGROUND: This is an updated version of the Cochrane review published in Issue
      4, 1998. Combining drugs from different classes with different modes of action
      may offer opportunity to optimise efficacy and tolerability, using lower doses of
      each drug to achieve the same degree of pain relief. Previously we concluded that
      addition of codeine to paracetamol provided additional pain relief, but at
      expense of additional adverse events. New studies have been published since. This
      review sought to evaluate efficacy and safety of paracetamol plus codeine using
      current data, and compare findings with other analgesics evaluated similarly.
      OBJECTIVES: Assess efficacy of single dose oral paracetamol plus codeine in acute
      postoperative pain, increase in efficacy due to the codeine component, and
      associated adverse events. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE,
      the Oxford Pain Relief Database in October 2008 for this update. SELECTION
      CRITERIA: Randomised, double-blind, placebo-controlled trials of paracetamol plus
      codeine, compared with placebo or the same dose of paracetamol alone, for relief
      of acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two authors
      assessed trial quality and extracted data. The area under the "pain relief versus
      time" curve was used to derive proportion of participants with paracetamol plus
      codeine and placebo or paracetamol alone experiencing least 50% pain relief over
      four-to-six hours, using validated equations. Number-needed-to-treat-to-benefit
      (NNT) was calculated using 95% confidence intervals (CIs). Proportion of
      participants using rescue analgesia over a specified time period, and time to use
      of rescue analgesia, were sought as additional measures of efficacy. Information
      on adverse events and withdrawals were collected. MAIN RESULTS: Twenty-six
      studies, with 2295 participants, were included comparing paracetamol plus codeine
      with placebo. Significant dose response was seen for the outcome of at least 50%
      pain relief over four-to-six hours, with NNTs of 2.2 (95% CI 1.8 to 2.9) for 800
      to 1000 mg paracetamol plus 60 mg codeine, 3.9 (2.9 to 4.5) for 600 to 650 mg
      paracetamol plus 60 mg codeine, and 6.9 (4.8 to 12) for 300 mg paracetamol plus
      30 mg codeine. Time to use of rescue medication was over four hours with
      paracetamol plus codeine and two hours with placebo. The NNT to prevent
      remedication was 5.6 (4.0 to 9.0) for 600 mg paracetamol plus 60 mg codeine over
      four to six hours. Adverse events increased of mainly mild to moderate severity
      with paracetamol plus codeine than placebo.Fourteen studies, with 926
      participants, were included in the comparison of paracetamol plus codeine with
      the same dose of paracetamol alone. Addition of codeine increased proportion of
      participants achieving at least 50% pain relief over four-to-six hours by 10 to
      15%, increased time to use of rescue medication by about one hour, and reduced
      proportion of participants needing rescue medication by about 15% (NNT to prevent
      remedication 6.9 (4.2 to 19). Adverse events were mainly mild to moderate in
      severity and incidence did not differ between groups. AUTHORS' CONCLUSIONS: This
      update confirms previous findings that combining paracetamol with codeine
      provided clinically useful levels of pain relief in about 50% of patients with
      moderate to severe postoperative pain, compared with under 20% with placebo. New
      information for remedication shows that the combination extended the duration of
      analgesia by about one hour compared to treatment with the same dose of
      paracetamol alone. At higher doses, more participants experienced adequate pain
      relief, but the amount of information available for the 1000 mg paracetamol plus
      60 mg codeine dose was small, and based on limited information.

PMID- 19160201
TI  - Tonsillectomy or adeno-tonsillectomy versus non-surgical treatment for
      chronic/recurrent acute tonsillitis.
AB  - BACKGROUND: Surgical removal of the tonsils, with or without adenoidectomy (adeno
      /tonsillectomy), is a common ENT operation but the indications for surgery are
      controversial. OBJECTIVES: To determine the effects of tonsillectomy, with and
      without adenoidectomy, in patients with chronic/recurrent acute tonsillitis.
      SEARCH STRATEGY: The Cochrane Ear, Nose and Throat Disorders Group Specialised
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2008, issue 2), MEDLINE (1966 to 2008), EMBASE (1974 to 2008),
      bibliographies, and additional sources were searched for published and
      unpublished trials. The date of the last search was 11 April 2008. SELECTION
      CRITERIA: Randomised controlled trials comparing tonsillectomy, with or without
      adenoidectomy, with non-surgical treatment in adults and children with
      chronic/recurrent acute tonsillitis. We included trials which used reduction in
      the number and severity of tonsillitis and sore throat as main outcome measures.
      DATA COLLECTION AND ANALYSIS: Two authors applied the inclusion/exclusion
      criteria independently. MAIN RESULTS: This review includes five studies: four
      undertaken in children (719 participants) and one in adults (70 participants).
      Good information about the effects of tonsillectomy is only available for
      children and for effects in the first year following surgery.Children were
      divided into two subgroups: those who are severely affected (based on specific
      criteria which are often referred to as the 'Paradise criteria') and those less
      severely affected.For more severely affected children adeno-/tonsillectomy will
      avoid three unpredictable episodes of any type of sore throat, including one
      episode of moderate or severe sore throat in the next year. The cost of this is a
      predictable episode of pain in the immediate postoperative period.Less severely
      affected children may never have had another severe sore throat anyway and the
      chance of them so doing is modestly reduced by adeno-/tonsillectomy. For them,
      surgery will mean having an average of two rather than three unpredictable
      episodes of any type of sore throat. The cost of this reduction is one inevitable
      and predictable episode of postoperative pain. The 'average' patient will have 17
      rather than 22 sore throat days but some of these 17 days (between five and
      seven) will be in the immediate postoperative period. Whilst the concept of the
      'average' patient is attractive, in practice, wide variability is likely.One
      reason why the impact of surgery is so modest, is that many untreated patients
      get better spontaneously. There is a trade-off for the physician and patient who
      must weigh up a number of different uncertainties: what proportion of my throat
      symptoms are attributable to my tonsils, and will I get better without any
      treatment? Similarly, the potential 'benefit' of surgery must be weighed against
      the risks of the procedure. AUTHORS' CONCLUSIONS: Adeno-/tonsillectomy is
      effective in reducing the number of episodes of sore throat and days with sore
      throats in children, the gain being more marked in those most severely affected.
      The size of the effect is modest, but there may be a benefit to knowing the
      precise timing of one episode of pain lasting several days - it occurs
      immediately after surgery as a direct consequence of it.It is clear that some
      children get better without any surgery, and that whilst removing the tonsils
      will always prevent 'tonsillitis', the impact of the procedure on 'sore throats'
      due to pharyngitis is much less predictable.

PMID- 19160202
TI  - Interventions for treating obesity in children.
AB  - BACKGROUND: Child and adolescent obesity is increasingly prevalent, and can be
      associated with significant short- and long-term health consequences. OBJECTIVES:
      To assess the efficacy of lifestyle, drug and surgical interventions for treating
      obesity in childhood. SEARCH STRATEGY: We searched CENTRAL on The Cochrane
      Library Issue 2 2008, MEDLINE, EMBASE, CINAHL, PsycINFO, ISI Web of Science, DARE
      and NHS EED. Searches were undertaken from 1985 to May 2008. References were
      checked. No language restrictions were applied. SELECTION CRITERIA: We selected
      randomised controlled trials (RCTs) of lifestyle (i.e. dietary, physical activity
      and/or behavioural therapy), drug and surgical interventions for treating obesity
      in children (mean age under 18 years) with or without the support of family
      members, with a minimum of six months follow up (three months for actual drug
      therapy). Interventions that specifically dealt with the treatment of eating
      disorders or type 2 diabetes, or included participants with a secondary or
      syndromic cause of obesity were excluded. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed trial quality and extracted data following the
      Cochrane Handbook. Where necessary authors were contacted for additional
      information. MAIN RESULTS: We included 64 RCTs (5230 participants). Lifestyle
      interventions focused on physical activity and sedentary behaviour in 12 studies,
      diet in 6 studies, and 36 concentrated on behaviorally orientated treatment
      programs. Three types of drug interventions (metformin, orlistat and sibutramine)
      were found in 10 studies. No surgical intervention was eligible for inclusion.
      The studies included varied greatly in intervention design, outcome measurements
      and methodological quality.Meta-analyses indicated a reduction in overweight at 6
      and 12 months follow up in: i) lifestyle interventions involving children; and
      ii) lifestyle interventions in adolescents with or without the addition of
      orlistat or sibutramine. A range of adverse effects was noted in drug RCTs.
      AUTHORS' CONCLUSIONS: While there is limited quality data to recommend one
      treatment program to be favoured over another, this review shows that combined
      behavioural lifestyle interventions compared to standard care or self-help can
      produce a significant and clinically meaningful reduction in overweight in
      children and adolescents. In obese adolescents, consideration should be given to
      the use of either orlistat or sibutramine, as an adjunct to lifestyle
      interventions, although this approach needs to be carefully weighed up against
      the potential for adverse effects. Furthermore, high quality research that
      considers psychosocial determinants for behaviour change, strategies to improve
      clinician-family interaction, and cost-effective programs for primary and
      community care is required.

PMID- 19160203
TI  - Inhaled corticosteroids for cystic fibrosis.
AB  - BACKGROUND: Reduction of lung inflammation is one of the goals of cystic fibrosis
      (CF) therapy. Inhaled corticosteroids (ICS) are often used to treat children and
      adults with CF. The rationale for this is their potential to reduce lung damage
      arising from inflammation, as well as their effect on symptomatic wheezing. It is
      important to establish the current level of evidence for the risks and benefits
      of ICS, especially in the light of their known adverse effects on growth.
      OBJECTIVES: To assess the effectiveness of taking regular ICS, compared to not
      taking them, in children and adults with CF. SEARCH STRATEGY: We searched the
      Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising
      references identified from comprehensive electronic database searches and
      handsearches of relevant journals and abstract books of conference proceedings.
      We requested information from pharmaceutical companies manufacturing inhaled
      corticosteroids and authors of identified trials.Date of most recent search of
      the Group's Trials Register: June 2008. SELECTION CRITERIA: Randomised or quasi
      randomised trials, published and unpublished, comparing ICS to placebo or
      standard treatment in individuals with CF. DATA COLLECTION AND ANALYSIS: Two
      independent authors assessed methodological quality of trials using established
      criteria and extracted data using standard pro formas. MAIN RESULTS: Thirty
      citations were identified by the searches, of which 25, representing 13 trials
      were eligible for inclusion. These 13 trials reported the use of ICS in 506
      people with CF aged between 6 and 55 years. One trial was a withdrawal study in
      individuals who were already taking ICS. Methodological quality was difficult to
      assess from published information. Inclusion criteria varied between trials, as
      did type and duration of treatment and timing of outcome assessments. Objective
      measures of airway function were reported in most trials but were often
      incomplete. Significant benefit has not been conclusively demonstrated. Four
      trials systematically documented adverse effects and growth was significantly
      affected in one study using high doses. AUTHORS' CONCLUSIONS: Evidence from these
      trials is insufficient to establish whether ICS are beneficial in CF, but
      withdrawal in those already taking them has been shown to be safe. There is some
      evidence they may cause harm in terms of growth. It has not been established
      whether long-term use is beneficial in reducing lung inflammation, which should
      improve survival, but it is unlikely this will be proven conclusively in a
      randomised controlled trial.

PMID- 19160204
TI  - Interventions for acute non-arteritic central retinal artery occlusion.
AB  - BACKGROUND: Acute central retinal artery occlusion (CRAO) occurs as a sudden
      interruption of the blood supply to the retina and results in an almost complete
      loss of vision in the affected eye. There is no generally agreed treatment
      regimen although a number of therapeutic interventions have been proposed.
      OBJECTIVES: The objective of this review was to examine the effects of treatments
      used for acute non-arteritic CRAO. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes
      and Vision Group Trials Register) (The Cochrane Library, Issue 3, 2008), MEDLINE
      (January 1966 to September 2008), EMBASE (January 1980 to September 2008) and the
      reference lists of relevant papers. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) only in which one treatment aimed to re-establish blood
      supply to the retina in people with acute CRAO was compared to another treatment.
      DATA COLLECTION AND ANALYSIS: Two authors independently assessed the search
      results for relevant trials. Discrepancies were resolved by discussion. MAIN
      RESULTS: We found two RCTs that met our inclusion criteria. AUTHORS' CONCLUSIONS:
      The included studies in this review were small and from single centres. Neither
      study was completely clear about it's method of treatment allocation. One study
      described the use of pentoxifylline tablets (three 600 mg tablets daily) and the
      other the use of enhanced external counterpulsation (EECP) combined with
      haemodilution. Both studies indicated improved retinal perfusion in the non
      control group but neither showed an improvement in vision. Large, well-designed
      RCTs are still required to establish the most effective treatment for acute CRAO.
      These studies should be looking at factors important to the patient i.e. improved
      vision with acceptable risk/side-effects.

PMID- 19160205
TI  - WITHDRAWN: Carbamazepine for cocaine dependence.
AB  - BACKGROUND: Cocaine dependence has become a public health problem, developing a
      significant number of medical, psychological and social problems. Although there
      is no consensus regarding how to treat cocaine dependence, effective
      pharmacotherapy has a potentially major role to play as part of a broader
      treatment milieu. The anti-convulsant carbamazepine, a tricyclic medication that
      is widely used to treat a variety of neurological and psychiatric disorders, has
      been used for treatment of cocaine dependence, although its effectiveness has not
      been established. OBJECTIVES: To determine whether carbamazepine is effective for
      the treatment of cocaine dependence. SEARCH STRATEGY: We searched: Cochrane
      Controlled Trials Register (Cochrane Library issue 1, 1999), MEDLINE (f1966 -
      October 1997), EMBASE (1980 - October 1997), PsycLIT (1974 - July 1997),
      Biological Abstracts and LILACS (1982 - 1997); scan of reference list of relevant
      articles; personal communication; conference abstracts; unpublished trials from
      pharmaceutical industry; book chapters on treatment of cocaine dependence. The
      specialised register of trials of Cochrane Group on Drugs and Alcohol until
      February 2003. SELECTION CRITERIA: All randomised controlled trials focused on
      the use of carbamazepine versus placebo on the treatment of cocaine dependence.
      Trials including patients with additional diagnosis such as opiate dependence
      were also eligible. DATA COLLECTION AND ANALYSIS: The reviewers extracted the
      data independently, Odds Ratios, weighted mean difference and number needed to
      treat were estimated. Qualitative assessments of the methodology of eligible
      studies were carried out using validated checklists. The reviewers assumed that
      people who died or dropped out had no improvement and tested the sensitivity of
      the final results to this assumption. Where possible analysis was carried out
      according to the "intention to treat" principles. MAIN RESULTS: 5 studies were
      included (455 participants). No differences regarding positive urine sample for
      cocaine metabolites. Scores on Spielberg State Anxiety Inventory slightly
      favoured carbamazepine, but not statistical significance. Dropouts were high in
      both groups, less dropout occurred in the carbamazepine group (RR 0.87 95%CI 0.71
      1.06). When no retention in treatment was due to side effects no differences were
      found. The number of participants presenting at least one side effect, was higher
      in the carbamazepine group (RR 4.33 95% CI 1.45-12.91). AUTHORS' CONCLUSIONS:
      There is no current evidence supporting the clinical use of Carbamazepine in the
      treatment of cocaine dependence. Larger randomised investigation must be
      considered taking into account that these time-consuming efforts should be
      reserved for medications showing more relevant and promising evidence.

PMID- 19160206
TI  - Nursing record systems: effects on nursing practice and healthcare outcomes.
AB  - BACKGROUND: A nursing record system is the record of care that was planned or
      given to individual patients and clients by qualified nurses or other caregivers
      under the direction of a qualified nurse. Nursing record systems may be an
      effective way of influencing nurse practice. OBJECTIVES: To assess the effects of
      nursing record systems on nursing practice and patient outcomes. SEARCH STRATEGY:
      For the original version of this review in 2000, and updates in 2003 and 2008, we
      searched: the Cochrane Effective Practice and Organisation of Care (EPOC) Group
      Specialised Register; MEDLINE, EMBASE, CINAHL, BNI, ISI Web of Knowledge, and
      ASLIB Index of Theses. We also handsearched: Computers, Informatics, Nursing
      (Computers in Nursing); Information Technology in Nursing; and the Journal of
      Nursing Administration. For this update, searches can be considered complete
      until the end of 2007. We checked reference lists of retrieved articles and other
      related reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs),
      controlled before and after studies, and interrupted time series comparing one
      kind of nursing record system with another in hospital, community or primary care
      settings. The participants were qualified nurses, students or healthcare
      assistants working under the direction of a qualified nurse, and patients
      receiving care recorded or planned using nursing record systems. DATA COLLECTION
      AND ANALYSIS: Two review authors (in two pairs) independently assessed trial
      quality and extracted data. MAIN RESULTS: We included nine trials (eight RCTs,
      one controlled before and after study) involving 1846 people. The studies that
      evaluated nursing record systems focusing on relatively discrete and focused
      problems, for example effective pain management in children, empowering pregnant
      women and parents, reducing loss of notes, reducing time spent on data entry of
      test results, reducing transcription errors, and reducing the number of pieces of
      paper in a record, all demonstrated some degree of success in achieving the
      desired results. Studies of nursing care planning systems and total nurse records
      demonstrated uncertain or equivocal results. AUTHORS' CONCLUSIONS: We found some
      limited evidence of effects on practice attributable to changes in record
      systems. It is clear from the literature that it is possible to set up the
      randomised trials or other quasi-experimental designs needed to produce evidence
      for practice. Qualitative nursing research to explore the relationship between
      practice and information use could be used as a precursor to the design and
      testing of nursing information systems.

PMID- 19160207
TI  - Antibiotics for spontaneous bacterial peritonitis in cirrhotic patients.
AB  - BACKGROUND: Spontaneous bacterial peritonitis is a complication of cirrhotic
      ascites that occurs in the absence of any intra-abdominal, surgically treatable
      source of infection. Antibiotic therapy is indicated and should be initiated as
      soon as possible to avoid severe complications that may lead to death. It has
      been proposed that empirical treatment should cover gram-negative enteric
      bacteria and gram-positive cocci, responsible for up to 90% of spontaneous
      bacterial peritonitis cases. OBJECTIVES: This review aims to evaluate the
      beneficial and harmful effects of different types and modes of antibiotic therapy
      in the treatment of spontaneous bacterial peritonitis in cirrhotic patients.
      SEARCH STRATEGY: We performed electronic searches in The Cochrane Hepato-Biliary
      Group Controlled Trials Register (July 2008), the Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library (Issue 3, 2008), MEDLINE
      (1950 to July 2008), EMBASE (1980 to July 2008), and Science Citation Index
      EXPANDED (1945 to July 2008). In addition, we handsearched the references of all
      identified studies and contacted the first author of each included trial.
      SELECTION CRITERIA: Randomised studies comparing different types of antibiotics
      for spontaneous bacterial peritonitis in cirrhotic patients. DATA COLLECTION AND
      ANALYSIS: Data were independently extracted from the trials by at least two
      authors. Peto odds ratios or average differences, with their 95% confidence
      intervals, were estimated. MAIN RESULTS: This systematic review attempted to
      summarise evidence from randomised clinical trials on the treatment of
      spontaneous bacterial peritonitis. Thirteen studies were included; each one of
      them compared different antibiotics in their experimental and control groups. No
      meta-analyses could be performed, though data on the main outcomes were collected
      and analysed separately for each included trial. Currently, the evidence showing
      that lower dosage or short-term treatment with third generation cephalosporins is
      as effective as higher dosage or long-term treatment is weak. Oral quinolones
      could be considered an option for those with less severe manifestations of the
      disease. AUTHORS' CONCLUSIONS: This review provides no clear evidence for the
      treatment of cirrhotic patients with spontaneous bacterial peritonitis. In
      practice, third generation cephalosporins have already been established as the
      standard treatment of spontaneous bacterial peritonitis, and it is clear, that
      empirical antibiotic therapy should be provided in any case. However, until
      large, well-conducted trials provide more information, practice will remain based
      on impression, not evidence.

PMID- 19160208
TI  - WITHDRAWN: Orthotic devices for treating patellofemoral pain syndrome.
AB  - BACKGROUND: Patellofemoral pain syndrome is a frequently reported condition in
      active adults. A wide variety of conservative treatment strategies have been
      described. As yet, no optimal strategy has been identified. Application of
      orthotic devices e.g. knee braces, knee straps, forms of taping of the knee,
      active training devices, knee sleeves and inlay soles to support the foot have
      been advocated to treat this condition. OBJECTIVES: To assess the effectiveness
      of foot and knee orthotics for treatment of patellofemoral pain syndrome. SEARCH
      STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group
      Specialised Register, the Cochrane Controlled Trials register (Issue 2, 2000),
      MEDLINE (January 1966 to March 2000; EMBASE (January 1988 to March 2000); CINAHL
      (January 1982 to March 2000) and PEDro (up to March 2000). Relevant orthotic
      companies were contacted. The date of the most recent search was May 2000.
      SELECTION CRITERIA: All randomised and quasi-randomised trials comparing the
      effectiveness of knee or foot orthotics for treatment of patellofemoral pain
      syndrome were selected. Trials describing the use of orthotic devices in
      conjunction with operative treatment were excluded. DATA COLLECTION AND ANALYSIS:
      Three reviewers independently assessed methodological quality of the identified
      trials by use of a modified version of the Cochrane Bone, Joint and Muscle Trauma
      Group assessment tool, consisting of 11 items. Two reviewers extracted data
      without blinding. Trialists were contacted to obtain missing data. MAIN RESULTS:
      Five trials involving 362 participants were included in this review. Five other
      trials await possible inclusion if further information can be obtained. Due to
      clinical heterogeneity, we refrained from statistical pooling and conducted
      analysis by grading the strength of scientific evidence. The level of obtained
      research-based evidence was graded as limited as all trials were of low
      methodological quality.This limited research-based evidence showed the Protonics
      brace at six week follow-up was significantly more effective for decrease in pain
      (weighted mean difference (WMD) between groups 3.2; 95% confidence interval (CI)
      2.8 to 3.6), functional improvement on the Kujala score (WMD 45.6; 95% CI 43.4 to
      47.7) and change in patellofemoral congruence angle (WMD 17.2; 95% CI 14.1 to
      20.3) when compared to no treatment. A comprehensive programme including tape
      application was significantly superior to a monitored exercise programme without
      tape application for decrease in worst pain (WMD 1.6; 95% CI 0.4 to 2.8) and
      usual pain (WMD 1.2; 95% CI 0.2 to 2.1), and clinical change and functional
      improvement questionnaire scores at four weeks follow-up.The trials reported
      statistically significant differences in patient satisfaction after applied
      therapy (WMD 3.3; 95% CI 0.5 to 6.1) in favour of the McConnell regimen compared
      with the Coumans bandage at six weeks follow-up. AUTHORS' CONCLUSIONS: The
      evidence from randomised controlled trials is currently too limited to draw
      definitive conclusions about the use of knee and foot orthotics for the treatment
      of patellofemoral pain. Future high quality trials in this field are warranted.

PMID- 19160209
TI  - WITHDRAWN: Biopsychosocial rehabilitation for upper limb repetitive strain
      injuries in working age adults.
AB  - BACKGROUND: Upper limb repetitive strain injury is a common problem in western
      countries, causing human suffering and huge economical losses. Patients with
      prolonged pain associated with repetitive tasks in the work place can face both
      psychological and physical difficulties. Different treatment programmes,
      physical, psychological, behavioural , social and occupational treatments have
      been developed and used to help these patients. OBJECTIVES: The objective of this
      systematic review is to determine the effectiveness of biopsychosocial
      rehabilitation for upper limb repetitive strain injuries among working age
      adults. SEARCH STRATEGY: The reviewed studies for this structured Cochrane review
      were identified from electronic bibliographic databases, the Science Citation
      Index, reference checking and consulting experts in the rehabilitation field. The
      original search was planned and performed for a more broad area of
      musculoskeletal disorders. Trials on repetitive strain injuries were separated
      afterwards. SELECTION CRITERIA: Randomised controlled trials and controlled
      trials comparing biopsychosocial measures for the treatment of repetitive upper
      limb strain injury in working age adults DATA COLLECTION AND ANALYSIS: Two
      experts in the field of rehabilitation evaluated the clinical relevance and
      applicability of the findings of the selected studies to actual clinical use. Two
      other blinded reviewers extracted the data and assessed the main results and the
      methodological quality of the studies using standardized forms. Finally, a
      qualitative analysis was performed to evaluate the level of scientific evidence
      for the effectiveness of biopsychosocial rehabilitation. MAIN RESULTS: We found
      only two relevant studies that satisfied our criteria. They assessed the
      effectiveness of two specific interventions and were both considered as low
      quality trials. The clinical relevance of the included studies was also
      unsatisfactory. The level of scientific evidence for the effectiveness of
      biopsychosocial rehabilitation for repetitive strain injuries was limited. One
      small trial found that hypnosis supplementary to comprehensive treatment can
      decrease the intensity of pain for acute RSI in six weeks follow-up. AUTHORS'
      CONCLUSIONS: We conclude that presently there appears to be little scientific
      evidence for the effectiveness of biopsychosocial rehabilitation on repetitive
      strain injuries. As RCTs on more intensive and comprehensive biopsychosocial
      treatment programmes for RSI are lacking, there does not seem to be reliable data
      for these interventions. There is a need for high quality trials in this field.

PMID- 19160210
TI  - WITHDRAWN: Interventions for tears of the rotator cuff in adults.
AB  - BACKGROUND: Tears of the rotator cuff tendons, which surround the joints of the
      shoulder, are one of the most common causes of pain and disability in the upper
      extremity. OBJECTIVES: To review the efficacy and safety of common interventions
      for tears of the rotator cuff in adults. SEARCH STRATEGY: We searched the
      Cochrane Bone, Joint and Muscle Trauma Group specialised trail register (July
      2002), the Cochrane Controlled Trials Register (The Cochrane Library issue 2,
      2002), MEDLINE (1966 to December 2001), EMBASE (1974 to December 2001),
      Biological Abstracts (1980 to December 2001), LILACS (1982 to December 2001),
      CINAHL (November 1982 to December 2001), Science Citation Index and reference
      lists of articles. We also contacted authors and handsearched conference
      proceedings focusing on shoulder conditions. SELECTION CRITERIA: Randomised or
      quasi-randomised clinical trials involving tears of the rotator cuff were the
      focus of this review. All trials involving conservative interventions or surgery
      were included (non-steroidal anti-inflammatory drugs, intra-articular or
      subacromial glucocorticosteroid injection, oral glucocorticosteroid treatment,
      physiotherapy, and open or arthroscopic surgery). DATA COLLECTION AND ANALYSIS:
      Two reviewers independently assessed suitability for inclusion, methodological
      quality and extracted data. Dichotomous data were presented as relative risks
      (RR) and 95% confidence intervals (CI), using the fixed effects model. MAIN
      RESULTS: Eight trials involving 455 people were included and 393 patients
      analysed. Trials were grouped in eight categories of conservative or surgical
      treatment. The median quality score of all trials combined was 16 out of a
      possible 24 points, with a range of 12-18. In general, included trials differed
      on diagnostic criteria for rotator cuff tear, there was no uniformity in reported
      outcome measures, and data which could be summarised were rarely reported. Only
      results from two studies comparing open repair to arthroscopic debridement could
      be pooled. There is weak evidence for the superiority of open repair of rotator
      cuff tears compared with arthroscopic debridement. AUTHORS' CONCLUSIONS: There is
      little evidence to support or refute the efficacy of common interventions for
      tears of rotator cuff in adults. As well as the need for further well designed
      clinical trials, uniform methods of defining interventions for rotator cuff tears
      and validated outcome measures are also essential.

PMID- 19160211
TI  - Non-invasive ventilation for cystic fibrosis.
AB  - BACKGROUND: Non-invasive ventilation (NIV) may be a means to temporarily reverse
      or slow the progression of respiratory failure in cystic fibrosis (CF).
      OBJECTIVES: To compare the effect of NIV versus no NIV in people with CF. SEARCH
      STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group
      Trials Register comprising references identified from comprehensive electronic
      database searches, handsearching relevant journals and abstract books of
      conference proceedings. We searched the reference lists of each trial for
      additional publications possibly containing other trials.Most recent search: June
      2008. SELECTION CRITERIA: Randomised controlled trials comparing a form of
      pressure preset or volume preset NIV to no NIV in people with acute or chronic
      respiratory failure in CF. DATA COLLECTION AND ANALYSIS: Three reviewers
      independently assessed trials for inclusion criteria and methodological quality,
      and extracted data. MAIN RESULTS: Fifteen trials were identified; seven trials
      met the inclusion criteria with a total of 106 participants. Six trials evaluated
      single treatment sessions and one evaluated a six-week intervention.Four trials
      (79 participants) evaluated NIV for airway clearance compared with an alternative
      chest physiotherapy method and showed that airway clearance may be easier with
      NIV and people with CF may prefer it. We were unable to find any evidence that
      NIV increases sputum expectoration, but it did improve some lung function
      parameters.Three trials (27 participants) evaluated NIV for overnight ventilatory
      support, measuring lung function, validated quality of life scores and nocturnal
      transcutaneous carbon dioxide. Due to the small numbers of participants and
      statistical issues, there were discrepancies in the results between the RevMan
      and the original trial analyses. No clear differences were found between NIV
      compared with oxygen or room air except for exercise performance, which
      significantly improved with NIV compared to room air over six weeks. AUTHORS'
      CONCLUSIONS: Non-invasive ventilation may be a useful adjunct to other airway
      clearance techniques, particularly in people with CF who have difficulty
      expectorating sputum. Non-invasive ventilation, used in addition to oxygen, may
      improve gas exchange during sleep to a greater extent than oxygen therapy alone
      in moderate to severe disease. These benefits of NIV have largely been
      demonstrated in single treatment sessions with small numbers of participants. The
      impact of this therapy on pulmonary exacerbations and disease progression remain
      unclear. There is a need for long-term randomised controlled trials which are
      adequately powered to determine the clinical effects of non-invasive ventilation
      in CF airway clearance and exercise.

PMID- 19160212
TI  - Budesonide for maintenance of remission in Crohn's disease.
AB  - BACKGROUND: Corticosteroids have been shown to be effective for induction, but
      not maintenance of remission in Crohn's disease. However, significant concerns
      exist regarding their risk for adverse events, particularly when used for long
      treatment courses. Budesonide is a glucocorticoid with limited systemic
      bioavailability due to extensive first-pass hepatic metabolism. Budesonide has
      been shown to be effective for induction of remission in Crohn's disease.
      OBJECTIVES: To evaluate the efficacy and safety of oral budesonide for
      maintenance of remission in Crohn's disease. SEARCH STRATEGY: The following
      electronic databases were searched: MEDLINE, EMBASE, the Cochrane Central
      Register of Controlled Trials, the Cochrane IBD/FBD Group Specialised Trial
      Register, and ClinicalTrials.gov. Reference lists of articles, as well as
      conference proceedings were manually searched. Study authors, study sponsors and
      pharmaceutical companies were also contacted. SELECTION CRITERIA: Randomized
      controlled trials comparing budesonide to a control treatment, or comparing two
      doses of budesonide, were included. The study population included patients of any
      age with Crohn's disease in remission. The primary outcome was maintenance of
      remission at various reported follow-up times during the study, up to 12 months
      following enrollment. Secondary outcomes included: time to relapse, mean change
      in CDAI, clinical, histological or endoscopic improvement, improvement in quality
      of life, adverse events and study withdrawal. DATA COLLECTION AND ANALYSIS: Two
      independent investigators reviewed studies for eligibility, extracted the data
      and assessed study quality using Jadad's criteria. A random or fixed effects
      model was chosen based on an assessment of heterogeneity, and studies were
      weighted using the DerSimonian & Laird or the Mantel-Haenszel method accordingly.
      Meta-analysis was performed using RevMan 4.2.10 software. MAIN RESULTS: Eleven
      studies were included in the review: 8 studies compared budesonide with placebo,
      one compared budesonide to 5-aminosalicylates, one compared budesonide to
      traditional systemic corticosteroids, and one compared two doses of budesonide
      with no control group. Eight studies used a controlled ileal release form of
      budesonide, while three used a pH-modified release formulation. Budesonide 6 mg
      daily was no more effective than placebo for maintenance of remission at 3 months
      (RR 1.25; 95% CI 1.00 to 1.58; P = 0.05), 6 months (RR 1.15; 95% CI 0.95 to 1.39;
      P = 0.14), or 12 months (RR 1.13; 95% CI 0.94 to 1.35; P = 0.19). Budesonide was
      not more effective than weaning doses of prednisolone for maintenance of
      remission at 12 months (RR 0.79; 95% CI 0.55 to 1.13; P = 0.20), but was better
      than mesalamine 3 grams per day (RR of remission 2.51; 95% CI 1.03 to 6.12; P =
      0.04). Budesonide 3 mg daily was more effective than placebo at 3 months (RR
      1.31; 95% CI 1.03 to 1.67; P = 0.03). This benefit was not sustained at 6 months
      (RR 1.10; 95% CI 0.81 to 1.50; P = 0.53), or 12 months (RR 1.04; 95% CI 0.84 to
      1.30; P = 0.70). No differences in efficacy were detected based on the different
      formulations of budesonide, methods used to induce remission, or budesonide dose.
      The use of budesonide 6 mg resulted in slight improvements in CDAI scores when
      assessed at 6 months (WMD -24.3; 95% CI -46.31 to -2.29; P = 0.03) and 12 months
      (WMD -23.49; 95% CI -46.65 to -0.32; P = 0.05) and mean time to relapse of
      disease (WMD 59.93 days; 95% CI 19.02 to 100.84; P = 0.004). Adverse events were
      more frequent in patients treated with 6 mg of budesonide compared with placebo
      (RR 1.49; 95% CI 1.01 to 2.19; P = 0.05), but not in patients using lower doses
      of budesonide. These events were relatively minor and did not result in increased
      rates of study withdrawal. Abnormal adrenocorticoid stimulation tests were seen
      more frequently in patients receiving both 6 mg daily (RR 2.88; 95% CI 1.72 to
      4.82; P < 0.0001) and 3 mg daily (RR 2.73; 95% CI 1.34 to 5.57; P = 0.006)
      compared with placebo. AUTHORS' CONCLUSIONS: Budesonide is not more effective
      than placebo or weaning prednisolone for maintenance of remission in Crohn's
      disease. Some modest benefits are noted in patients receiving budesonide compared
      with placebo in terms of lower CDAI scores and longer time to relapse of disease.
      However, these benefits are offset by higher treatment-related adverse event
      rates and more frequent adrenocorticoid suppression in patients receiving
      budesonide. Therefore, budesonide is not recommended for maintenance of remission
      in Crohn's disease.

PMID- 19160213
TI  - Nutrition support for bone marrow transplant patients.
AB  - BACKGROUND: This is an update of the original Cochrane review published in Issue
      2, 2002. Bone marrow transplantation involves administration of toxic
      chemotherapy and infusion of marrow cells. After treatment, patients can develop
      poor appetite, mucositis and gastrointestinal failure, leading to malnutrition.
      To prevent this, parenteral nutrition (PN) support is often first choice but is
      associated with increased risk of infection. Enteral nutrition (EN) is an
      alternative, as is addition of substrates. OBJECTIVES: To determine efficacy of
      EN or PN support for patients receiving bone marrow transplant. SEARCH STRATEGY:
      Search of The Cochrane Library, MEDLINE, EMBASE and CINAHL in November 2000 and
      subsequently June 2006. SELECTION CRITERIA: RCTs that compared one form of
      nutrition support with another, or control, for bone marrow transplant patients.
      DATA COLLECTION AND ANALYSIS: Twenty nine studies were identified. Data were
      collected on participants' characteristics; adverse effects; neutropaenia; %
      change in body weight; graft versus host disease; and survival. MAIN RESULTS: In
      two studies (82 participants) glutamine mouthwash reduced number of days patients
      were neutropenic (6.82 days, 95%CI (1.67 to 11.98) P = 0.009) compared with
      placebo. Three studies reported (103 participants) that patients receiving PN
      with glutamine had reduced hospital stay, 6.62 d (95%CI 3.47 to 9.77, P =
      0.00004) compared with patients receiving standard PN. However, in the update a
      further study was added (147 participants) which altered the pooled results:
      duration in hospital may be increased for those who receive PN with additional
      glutamine - 0.22 days (95%CI (1.29 to 1.72). Two other studies reported that (73
      participants) patients receiving PN plus glutamine had reduced incidence of
      positive blood cultures (OR 0.23, 95%CI 0.08 to 0.65, P = 0.006) compared to
      those receiving standard PN. However, a study from the update (113 participants
      in total) showed the odds of having a positive blood culture have increased but
      are still less likely if the patient receives PN with glutamine compared to
      standard PN (OR 0.46, 95%CI 0.20 to 1.04). When patients were given PN versus IV
      hydration, (25 participants) patients receiving PN had a higher incidence of line
      infections (OR 21.23, 95%CI 4.15 to 108.73, P = 0.0002) compared to those
      receiving standard IV fluids. The update identified one study which recognised
      that (55 participants) those who received IV were likely to spend less time in
      hospital, 3.30 days (95%CI -0.38 to 6.98, P = 0.08), although this result was not
      significant. As reported in the original review there remains no evaluable data
      to properly compare PN with EN. AUTHORS' CONCLUSIONS: In this update an
      additional study that compared PN and Glutamine versus standard PN showed that
      the certain benefits of parenteral nutrition with added glutamine compared to
      standard PN for reducing hospital stay are no longer definite. When PN with
      glutamine is compared with standard PN, patients may not leave hospital earlier,
      but do have reduced incidence of positive blood cultures, than those receiving
      standard PN. Where possible use of intravenous fluids and oral diet should be
      considered as a preference to parenteral nutrition, however, in the event of a
      patient suffering severe gastrointestinal failure even with a trial of enteral
      feeding, PN with the addition of glutamine could be considered.

PMID- 19160214
TI  - Dietary interventions for recurrent abdominal pain (RAP) and irritable bowel
      syndrome (IBS) in childhood.
AB  - BACKGROUND: Between 4% and 25% of school-age children complain of recurrent
      abdominal pain (RAP) of sufficient severity to interfere with daily activities.
      It is unclear whether the diagnosis includes children with different aetiologies
      for their pain. For the majority no organic cause for their pain can be found on
      physical examination or investigation. Although most children are likely managed
      by reassurance and simple measures, a large range of interventions have been
      recommended. OBJECTIVES: To determine the effectiveness of dietary interventions
      for recurrent abdominal pain in school-age children. SEARCH STRATEGY: The
      Cochrane Library (CENTRAL) 2006 (Issue 4), MEDLINE (1966 to Dec 2006), EMBASE
      (1980 to Dec 2006), CINAHL (1982 to Dec 2007), ERIC (1966 to Dec 2006), PsycINFO
      (1872 to Dec 2006), LILACS (1982 to Dec 2006), SIGLE (1980 to March 2005), and
      JICST (1985 to 06/2000) were searched . Where appropriate, search filters were
      employed. Researchers working in this area were asked to identify relevant
      studies. SELECTION CRITERIA: Randomised or quasi-randomised studies of any
      dietary treatment versus placebo or no treatment in school-age children with a
      diagnosis of RAP or functional gastrointestinal disorder based on the Rome II
      criteria. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials
      for inclusion, assessed quality and extracted data. Where appropriate studies
      were pooled using a random effects meta-analysis. MAIN RESULTS: Seven trials were
      included in this review. Two trials, including 83 participants, compared fibre
      supplements with placebo (Christensen 1982, Feldman 1985), with data from one
      study reported in two papers (Christensen 1982, Christensen 1986). The pooled
      odds ratio for improvement in the frequency of abdominal pain was 1.26 (0.25,
      6.29). Two trials, including 90 participants (Lebenthal 1981, Dearlove 1983)
      compared lactose-containing with lactose-free diets. Neither reported data in a
      form which could be used in the meta-analysis and the former trial had a loss to
      follow-up of 45%. We were not able to obtain further data for either trial. Three
      trials (Bausserman 2005, Gavronska 2007, Young 1997) comparing supplementation
      with Lactobacillus with placebo met the inclusion criteria but only two
      (Bausserman 2005, Gavronska 2007), including a total of 168 children, provided
      analysable data. The pooled odds ratio for improvement of symptoms was 1.17 (95%
      CI 0.62, 2.21). AUTHORS' CONCLUSIONS: There is a lack of high quality evidence on
      the effectiveness of dietary interventions. This review provides no evidence that
      fibre supplements, lactose free diets or lactobacillus supplementation are
      effective in the management of children with RAP.

PMID- 19160215
TI  - Treatment for amphetamine psychosis.
AB  - BACKGROUND: Chronic amphetamine users may have experience of paranoia and
      hallucination. It has long been believed that dopamine antagonists, such as
      chlorpromazine, haloperidol, and thioridazine, are effective for the treatment of
      amphetamine psychosis. OBJECTIVES: To evaluate risks, benefits, costs of
      treatments for amphetamine psychosis. SEARCH STRATEGY: MEDLINE (1966-2007),
      EMBASE (1980-2007), CINAHL (1982-2007), PsychINFO (1806-2007), CENTRAL (Cochrane
      Library 2008 issue 1), references of obtained articles. SELECTION CRITERIA: All
      randomised controlled and clinical trials (RCTs, CCTs) evaluating treatments
      (alone or combined) for people with amphetamine psychosis DATA COLLECTION AND
      ANALYSIS: Two authors evaluated and extracted the data independently. Dichotomous
      data were extracted on an intention-to-treat basis in which the dropouts were
      assigned as participants with the worst outcomes. The Relative Risk (RR) with the
      95% confidence interval (95% CI) was used to assess the dichotomous data. The
      Weighted Mean Difference (WMD) with 95% CI was used to assess the continuous
      data. MAIN RESULTS: The comprehensive searches found one randomised controlled
      trial of treatment for amphetamine psychosis meeting the criteria for considering
      studies. The study involved 58 participants and compared the efficacy and
      tolerability of two antipsychotic drugs, olanzapine (a newer antipsychotic) and
      haloperidol (a commonly used antipsychotic medication used as a control
      condition), in treating amphetamine-induced psychosis. The results show that both
      olanzapine and haloperidol at clinically relevant doses were efficacious in
      resolving psychotic symptoms, with the olanzapine condition showing significantly
      greater safety and tolerability than the haloperidol control as measured by
      frequency and severity of extrapyramidal symptoms. AUTHORS' CONCLUSIONS: Only one
      RCT of treatment for amphetamine psychosis has been published. Outcomes from this
      trial indicate that antipsychotic medications effectively reduce symptoms of
      amphetamine psychosis, the newer generation and more expensive antipsychotic
      medication, olanzapine, demonstrates significantly better tolerability than the
      more affordable and commonly used medication, haloperidol.There are other two
      studies that did not meet the inclusion criteria for this review. The results of
      these two studies show that agitation and some psychotic symptoms may be abated
      within an hour after antipsychotic injection.Whether this limited evidence can be
      applied for amphetamine psychotic patients is not yet known.The medications that
      should be further investigate are conventional antipsychotics, newer
      antipsychotics and benzodiazepines. However, naturalistic studies of amphetamine
      psychotic symptoms and the prevalence of relapse to psychosis in the presence of
      amphetamine, are also crucial for advising the development of study designs
      appropriate for further treatment studies of amphetamine psychosis.

PMID- 19160216
TI  - Ginkgo biloba for cognitive impairment and dementia.
AB  - BACKGROUND: Extracts of the leaves of the maidenhair tree, Ginkgo biloba, have
      long been used in China as a traditional medicine for various disorders of
      health. A standardized extract is widely prescribed for the treatment of a range
      of conditions including memory and concentration problems, confusion, depression,
      anxiety, dizziness, tinnitus and headache. The mechanisms of action are thought
      to reflect the action of several components of the extract and include increasing
      blood supply by dilating blood vessels, reducing blood viscosity, modification of
      neurotransmitter systems, and reducing the density of oxygen free radicals.
      OBJECTIVES: To assess the efficacy and safety of Ginkgo biloba for dementia or
      cognitive decline. SEARCH STRATEGY: The Specialized Register of the Cochrane
      Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE,
      EMBASE, PsycINFO, CINAHL and LILACS were searched on 20 September 2007 using the
      terms: ginkgo*, tanakan, EGB-761, EGB761, "EGB 761" and gingko*. The CDCIG
      Specialized Register contains records from all major health care databases (The
      Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many
      trials databases and grey literature sources. SELECTION CRITERIA: Randomized,
      double-blind studies, in which extracts of Ginkgo biloba at any strength and over
      any period were compared with placebo for their effects on people with acquired
      cognitive impairment, including dementia, of any degree of severity. DATA
      COLLECTION AND ANALYSIS: Data were extracted from the published reports of the
      included studies, pooled where appropriate and the treatment effects or the risks
      and benefits estimated. MAIN RESULTS: 36 trials were included but most were small
      and of duration less than three months. Nine trials were of six months duration
      (2016 patients). These longer trials were the more recent trials and generally
      were of adequate size, and conducted to a reasonable standard. Most trials tested
      the same standardised preparation of Ginkgo biloba, EGb 761, at different doses,
      which are classified as high or low. The results from the more recent trials
      showed inconsistent results for cognition, activities of daily living, mood,
      depression and carer burden. Of the four most recent trials to report results
      three found no difference between Ginkgo biloba and placebo, and one found very
      large treatment effects in favour of Ginkgo biloba.There are no significant
      differences between Ginkgo biloba and placebo in the proportion of participants
      experiencing adverse events.A subgroup analysis including only patients diagnosed
      with Alzheimer's disease (925 patients from nine trials) also showed no
      consistent pattern of any benefit associated with Ginkgo biloba. AUTHORS'
      CONCLUSIONS: Ginkgo biloba appears to be safe in use with no excess side effects
      compared with placebo. Many of the early trials used unsatisfactory methods, were
      small, and publication bias cannot be excluded. The evidence that Ginkgo biloba
      has predictable and clinically significant benefit for people with dementia or
      cognitive impairment is inconsistent and unreliable.

PMID- 19160217
TI  - Acetylcysteine and carbocysteine for acute upper and lower respiratory tract
      infections in paediatric patients without chronic broncho-pulmonary disease.
AB  - BACKGROUND: Acetylcysteine and carbocysteine are the most commonly prescribed
      mucolytic drugs in many European countries. To our knowledge, no systematic
      review has been published on their efficacy and safety for acute upper and lower
      respiratory tract infections (ARTIs) in children without chronic broncho
      pulmonary disease. OBJECTIVES: The objective was to assess the efficacy and
      safety and to establish a benefit-risk ratio of acetylcysteine and carbocysteine
      as symptomatic treatments for ARTIs in children without chronic broncho-pulmonary
      disease. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library 2007, issue 4) which contains the Acute
      Respiratory Infections (ARI) Group's Specialized Register, MEDLINE (1966 to
      2008), EMBASE (1980 to 2008); Micromedex (2008), Pascal (1987 to 2004), and
      Science Citation Index (1974 to 2008). SELECTION CRITERIA: To study efficacy, we
      used randomised controlled trials (RCTs) comparing the use of acetylcysteine or
      carbocysteine versus placebo either alone or as an add-on therapy.To study
      safety, we also used trials comparing the use of acetylcysteine or carbocysteine
      versus active treatment or no treatment and case reports. DATA COLLECTION AND
      ANALYSIS: At least two review authors extracted data and assessed trial quality.
      We performed a subgroup analysis of children younger than two years of age. MAIN
      RESULTS: Six trials involving 497 participants were included to study efficacy.
      They showed some benefit from mucolytic agents, although differences were of
      little clinical relevance. No conclusion was drawn about the subgroup of infants
      younger than two years because the data were unavailable. Thirty-four studies
      including the previous six trials involving 2064 children were eligible to study
      safety. Overall safety was good but very few data were available to evaluate
      safety in infants younger than two years. However, 48 cases of paradoxically
      increased bronchorrhoea observed in infants were reported to the French
      pharmacovigilance system. AUTHORS' CONCLUSIONS: The results of this review have
      to be interpreted with caution because it was based on a limited number of
      participants included in studies whose methodological quality is questionable.
      Acetylcysteine and carbocysteine seem to have a limited efficacy and appear to be
      safe in children older than two years. These results should take into
      consideration the fact that acetylcysteine and carbocysteine are prescribed for
      self-limiting diseases (for example, acute cough, bronchitis). Regarding children
      younger than two years, given concerns about safety, these drugs should only be
      used for ARTIs in the context of an RCT.

PMID- 19160218
TI  - WITHDRAWN: Antibiotics / anti-inflammatories for reducing acute inflammatory
      episodes in lymphoedema of the limbs.
AB  - BACKGROUND: Lymphoedema is a chronic, progressive condition and one area of
      debate is the optimum management for infective/inflammatory episodes (AIE's).
      OBJECTIVES: To determine whether antibiotic/anti-inflammatory drugs given
      prophylactically reduce the number and severity of AIE's in patients with
      lymphoedema. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group
      register in September 2003, the Cochrane Central Register of Controlled Trials
      (The Cochrane Library, Issue 4, 2003), CINAHL, MEDLINE, PASCAL, SIGLE, UnCover,
      reference lists produced by The British Lymphology Society, the National Research
      Register (NRR) and the International Society of Lymphology congress proceedings.
      SELECTION CRITERIA: Randomised controlled trials testing an antibiotic or anti
      inflammatory drug against placebo (with or without physical therapies) were
      included. DATA COLLECTION AND ANALYSIS: Eligibility for inclusion was confirmed
      by two blinded reviewers. The papers were screened independently using a
      checklist of criteria relating to quality. Both reviewers extracted data from the
      eligible studies using a data extraction form. MAIN RESULTS: Four studies (364
      randomised patients) were included. Two studied the effects of intensive physical
      treatment plus selenium or placebo in preventing AIE's, and two studied the
      effects of Ivermectin, Diethylcarbamazine (DEC) (anti-filarial agents) and
      penicillin as prophylactic treatment for adeno lymphangitis(ADL) versus
      placebo.Both selenium trials reported no inflammatory episodes during the trial
      period in the treated group but one case of infection in the two placebo groups
      respectively. Seven additional cases of infection in trial one and 14 cases in
      trial two required treatment in the three month follow up period.One anti
      filarial trial reported 127 ADL episodes for all groups during the treatment year
      (compared with 684 episodes during the pre-treatment year). There were 228 ADL
      episodes during the trial follow-up year but no findings were significant. No
      link was found between the grade of oedema and the frequency of ADL episodes.
      There was a significant link between increased episodes and the rainy season.
      Penicillin reduced the mean number of inflammatory episodes from 4.6 to 0.5 after
      treatment, which increased to 1.9 at the end of follow-up. AUTHORS' CONCLUSIONS:
      The effectiveness of selenium in preventing AIE in lymphoedema remains
      inconclusive in the absence of properly conducted randomised-controlled trials.
      Anti-filarials do not appear to reduce ADL episodes in filarial lymphoedema.
      Penicillin appears to contribute to a significant reduction in ADL when combined
      with foot-care. The importance of foot-care should be recommended, which may also
      apply to care of the arm following breast cancer treatment. Properly conducted
      trials are needed to demonstrate any efficacy of these interventions.

PMID- 19160219
TI  - Immunosuppressant and immunomodulatory treatments for multifocal motor
      neuropathy.
AB  - BACKGROUND: Multifocal motor neuropathy is characterised by progressive,
      predominantly distal, asymmetrical limb weakness and usually multiple partial
      motor nerve conduction blocks. Intravenous immunoglobulin is beneficial but the
      role of immunosuppressive agents is uncertain. OBJECTIVES: To provide the best
      available evidence from randomised controlled trials on the role of
      immunosuppressive agents for the treatment of multifocal motor neuropathy. SEARCH
      STRATEGY: For this update, we searched the Cochrane Neuromuscular Disease Group
      Trials Register (October 8 2008), the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE (from January 1966
      to October 8 2008), and EMBASE (from January 1980 to October 8 2008), for trials
      of multifocal motor neuropathy. SELECTION CRITERIA: Randomised and quasi
      randomised controlled trials were to be included and one was found. Prospective
      and retrospective case series and case reports were considered in the Discussion.
      DATA COLLECTION AND ANALYSIS: Two review authors searched the titles and
      abstracts of the articles identified and extracted the data independently. MAIN
      RESULTS: In this update, we found the first randomised controlled trial of
      multifocal motor neuropathy. This study, which randomised 28 patients, showed
      that mycophenolate mofetil did not significantly improve strength or function or
      reduce the need for intravenous immunoglobulin. We summarised the results of
      retrospective and prospective case series in the discussion. AUTHORS'
      CONCLUSIONS: In the only randomised placebo-controlled trial of any
      immunosuppressive agent, mycophenolate mofetil did not produce significant
      benefit. Trials of other immunosuppressants should be undertaken.

PMID- 19160220
TI  - Interventions for haemolytic uraemic syndrome and thrombotic thrombocytopenic
      purpura.
AB  - BACKGROUND: Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic
      purpura (TTP) are related conditions with similar clinical features of variable
      severity. Survival of patients with HUS and TTP has improved greatly over the
      past two decades with improved supportive care for patients with HUS and by the
      use of plasma exchange (PE) with fresh frozen plasma (FFP) for patients with TTP.
      Separate pathogenesis of these two disorders has become more evident, but
      management overlaps. OBJECTIVES: To evaluate the benefits and harms of different
      interventions for HUS and TTP separately, in patients of all ages. SEARCH
      STRATEGY: We searched MEDLINE, EMBASE, the Cochrane Central Register of
      Controlled Trials (CENTRAL), conference proceedings, reference lists of articles
      and text books and contact with investigators were used to identify relevant
      studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating any
      interventions for HUS or TTP in patients of all ages. DATA COLLECTION AND
      ANALYSIS: Three authors independently extracted data and evaluated study
      reporting quality using standard Cochrane criteria. Analysis was undertaken using
      a random effects model and results expressed as risk ratio (RR) and 95%
      confidence intervals (CI). MAIN RESULTS: For TTP, we found six RCTs (331
      participants) evaluating PE with FFP as the control. Interventions tested
      included antiplatelet therapy (APT) plus PE with FFP, FFP transfusion and PE with
      cryosupernatant plasma (CSP). Two studies compared plasma infusion (PI) to PE
      with FFP and showed a significant increase in failure of remission at two weeks
      (RR 1.48, 95% 1.12 to 1.96) and all-cause mortality (RR 1.91, 95% 1.09 to 3.33)
      in the PI group. Seven RCTs were undertaken in children with HUS. None of the
      assessed interventions used (FFP transfusion, heparin with or without urokinase
      or dipyridamole, shiga toxin binding protein and steroids) were superior to
      supportive therapy alone, for all-cause mortality, neurological/extrarenal
      events, renal biopsy changes, proteinuria or hypertension at the last follow-up
      visit. Bleeding was significantly higher in those receiving anticoagulation
      therapy compared to supportive therapy alone (RR 25.89, 95% CI 3.67 to 182.83).
      AUTHORS' CONCLUSIONS: PE with FFP is still the most effective treatment available
      for TTP. For patients with HUS, supportive therapy including dialysis is still
      the most effective treatment. All studies in HUS have been conducted in the
      diarrhoeal form of the disease. There were no RCTs evaluating the effectiveness
      of any interventions on patients with atypical HUS who have a more chronic and
      relapsing course.

PMID- 19160221
TI  - WITHDRAWN: Interventions for treating acute Achilles tendon ruptures.
AB  - BACKGROUND: There is lack of consensus on the best management of the acute
      Achilles tendon (TA) rupture. Treatment can be broadly classified into operative
      (open or percutaneous) and non-operative (cast immobilisation or functional
      bracing). Post-operative splintage can be with a rigid cast (above or below the
      knee) or a more mobile functional brace. OBJECTIVES: To identify and summarise
      the evidence from randomised controlled trials of the effectiveness of different
      interventions in the treatment of acute Achilles tendon ruptures. SEARCH
      STRATEGY: We searched multiple databases including the Cochrane Musculoskeletal
      Injuries Group specialised register (to September 2003), reference lists of
      articles and contacted trialists. Keywords included Achilles Tendon, Rupture, and
      Tendon Injuries. SELECTION CRITERIA: All randomised and quasi-randomised trials
      comparing different treatment regimens for acute Achilles tendon ruptures. DATA
      COLLECTION AND ANALYSIS: Three reviewers extracted data and independently
      assessed trial quality by use of a ten-item scale. MAIN RESULTS: Fourteen trials
      involving 891 patients were included. Several of the studies had poor methodology
      and inadequate reporting of outcomes.Open operative treatment compared with non
      operative treatment (4 trials, 356 patients) was associated with a lower risk of
      rerupture (relative risk (RR) 0.27, 95% confidence interval (CI) 0.11 to 0.64),
      but a higher risk of other complications including infection, adhesions and
      disturbed skin sensibility (RR 10.60, 95%CI 4.82 to 23.28).Percutaneous repair
      compared with open operative repair (2 studies, 94 patients) was associated with
      a shorter operation duration, and lower risk of infection (RR 10.52, 95% CI 1.37
      to 80.52). These figures should be interpreted with caution because of the small
      numbers involved.Patients splinted with a functional brace rather than a cast
      post-operatively (5 studies, 273 patients) tended to have a shorter in-patient
      stay, less time off work and a quicker return to sporting activities. There was
      also a lower complication rate (excluding rerupture) in the functional brace
      group (RR 1.88 95%CI 1.27 to 2.76).Because of the small number of patients
      involved no definitive conclusions could be made regarding different operative
      techniques (1 study, 51 patients), different non-operative treatment regimes (2
      studies, 90 patients), and different forms of post-operative cast immobilisation
      (1 study, 40 patients). AUTHORS' CONCLUSIONS: Open operative treatment of acute
      Achilles tendon ruptures significantly reduces the risk of rerupture compared to
      non-operative treatment, but produces a significantly higher risk of other
      complications, including wound infection. The latter may be reduced by performing
      surgery percutaneously. Post-operative splintage in a functional brace appears to
      reduce hospital stay, time off work and sports, and may lower the overall
      complication rate.

PMID- 19160222
TI  - Orthotic devices after stroke and other non-progressive brain lesions.
AB  - BACKGROUND: Post-stroke motor impairments cause difficulty controlling the joints
      of the affected limbs to produce useful movements. One way to manage this to use
      an orthosis to control the movement of the affected joints but evidence for their
      benefit is lacking. OBJECTIVES: To determine the effectiveness of upper or lower
      limb orthoses on activity and impairment in people with stroke and other non
      progressive brain lesions. SEARCH STRATEGY: In February 2007 we searched the
      trials registers of the Cochrane Stroke, Movement Disorders and Injuries Groups,
      the Cochrane Database of Systematic Reviews and the Cochrane Central Register of
      Controlled Trials (The Cochrane Library Issue 1, 2007), MEDLINE (from 1966),
      EMBASE (from 1980), CINAHL (from 1983), AMED (from 1985), PsycINFO (from 1967)
      and RECAL (from 1990), and other databases and trials registers. We screened
      reference lists, contacted lead authors and other researchers in the field.
      SELECTION CRITERIA: We included randomised controlled trials of orthoses applied
      to the upper or lower limb in people with stroke and other non-progressive brain
      lesions. DATA COLLECTION AND ANALYSIS: Two review authors independently
      identified trials, extracted data, and assessed trial quality. Results for
      continuous outcomes were combined and analysed using mean difference or
      standardised mean difference, both with 95% confidence intervals and fixed-effect
      model. MAIN RESULTS: We analysed 14 trials with 429 participants. The overall
      effect of lower limb orthoses on walking disability (speed), walking impairment
      (step/stride length) and balance impairment (weight distribution in standing) was
      significant and beneficial. There was no significant effect on postural sway
      (balance impairment) or mobility disability but the numbers of studies and
      participants were low. However, these were all cross-over trials that looked at
      the immediate effect while wearing the orthosis; they did not assess the effects
      of wearing an orthosis over the long term. Upper limb orthoses showed no effect
      on upper limb function, range of movement at the wrist, fingers or thumb, nor
      pain. However, this was based on only three trials. AUTHORS' CONCLUSIONS: A lower
      limb orthosis can improve walking and balance but the included studies have only
      examined the immediate effects while wearing the orthosis; the effects of long
      term use have not been investigated. An upper limb orthosis does not effect on
      upper limb function, range of movement at the wrist, fingers or thumb, nor pain,
      but this conclusion is based on only three trials.

PMID- 19160223
TI  - Transmyocardial laser revascularization versus medical therapy for refractory
      angina.
AB  - BACKGROUND: Chronic angina and advanced forms of coronary disease are
      increasingly more frequent. Although the improved efficacy of available
      revascularization treatments, a subgroup of patients present with refractory
      angina. Transmyocardial laser revascularization (TMLR) has been proposed to
      improve the clinical situation of these patients. OBJECTIVES: To assess the
      efficacy and safety of TMLR versus optimal medical treatment in patients with
      refractory angina in alleviating the severity of angina and improving
      survivorship and heart function. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials on The Cochrane Library (Issue 2 2007),
      MEDLINE (January 2006 to June 2007), EMBASE ( 2004 to June 2007) and ongoing
      studies were sought using the metaRegister of Controlled Trials database (mRCT)
      and ClinicalTrials.gov databases. No languages restrictions were applied.
      Reference lists of relevant papers were also checked. SELECTION CRITERIA: Studies
      were selected if they fulfilled the following criteria: randomized controlled
      trials of TMLR, by thoracotomy, in patients with angina grade III-IV who were
      excluded from other revascularization procedures. From a total of 181 references,
      20 papers were selected, reporting data from seven studies. DATA COLLECTION AND
      ANALYSIS: Two reviewers abstracted data from selected papers; . The reviewers
      performed independently both quality assessment and data extraction. Selected
      studies present methodological weaknesses. None of them fulfilled all the quality
      criteria. MAIN RESULTS: Seven studies (1137 participants of which 559 randomized
      to TMLR) were included. Overall, 43.8 % of patients in the treatment group
      decreased two angina classes as compared with 14.8 % in the control group, odds
      ratio (OR) of 4.63 (95% confidence interval (CI) 3.43 to 6.25), and heterogeneity
      was statistically significant. Mortality by intention-to-treat analysis at both
      30 days (4.0 % in the TMLR group and 3.5 % in the control group) and 1 year (12.2
      % in the TMLR group and 11.9 % in the control group) was similar in both groups.
      The 30-days mortality as treated was 6.8% in TMLR group and 0.8% in the control
      group, showing a statistically significant difference. The pooled OR was 3.76
      (95% CI 1.63 to 8.66), because of the higher mortality in patients crossing from
      standard treatment to TMLR. AUTHORS' CONCLUSIONS: There is insufficient evidence
      to conclude that the clinical benefits of TMLR outweigh the potential risks. The
      procedure is associated with a significant early mortality.

PMID- 19160224
TI  - Hormone replacement therapy to maintain cognitive function in women with
      dementia.
AB  - BACKGROUND: As estrogens have been shown to have several potentially beneficial
      effects on the central nervous system, it is biologically plausible that
      maintaining high levels of estrogens in postmenopausal women by means of estrogen
      replacement therapy (ERT) could be protective against cognitive decline in women
      with Alzheimer's disease (AD) or other dementia syndromes. OBJECTIVES: To
      investigate the effects of ERT (estrogens only) or HRT (estrogens combined with a
      progestagen) compared with placebo in randomized controlled trials (RCTs) on
      cognitive function of postmenopausal women with dementia. SEARCH STRATEGY: The
      Cochrane Dementia and Cognitive Improvement Group Specialized Register, which
      contains records from many medical databases, The Cochrane Library, EMBASE,
      MEDLINE, CINAHL, PsycINFO and LILACS were searched on 7 November 2007 using the
      terms ORT, PORT, ERT, HRT, estrogen*, oestrogen* and progesterone*. SELECTION
      CRITERIA: All double-blind randomized controlled trials (RCTs) into the effect of
      ERT or HRT for cognitive function with a treatment period of at least two weeks
      in postmenopausal women with AD or other types of dementia. DATA COLLECTION AND
      ANALYSIS: Abstracts of the references retrieved by the searches were read by two
      reviewers (EH and KY) independently in order to discard those that were clearly
      not eligible for inclusion. The two reviewers studied the full text of the
      remaining references and independently selected studies for inclusion. Any
      disparity in the ensuing lists was resolved by discussion with all reviewers in
      order to arrive at the final list of included studies. The selection criteria
      ensured that the blinding and randomization of the included studies was adequate.
      The two reviewers also assessed the quality of other aspects of the included
      trials. One reviewer (EH) extracted the data from the studies, but was aided and
      checked by JB from Cochrane. MAIN RESULTS: A total of seven trials including 351
      women with AD were analysed. Because different drugs were used at different
      studies it was not possible to combine more than two studies in any analysis.On a
      clinical global rating, clinicians scored patients taking CEE as significantly
      worse compared with the placebo group on the Clinical Dementia Rating scale after
      12 months (overall WMD = 0.35, 95% CI = 0.01 to 0.69, z = 1.99, P <
      0.05).Patients taking CEE had a worse performance on the delayed recall of the
      Paragraph Test (overall WMD = -0.45, 95% CI = -0.79 to -0.11, z = 2.60, P < 0.01)
      after one month than those taking placebo. They had a worse performance on Finger
      Tapping after 12 months (WMD = -3.90, 95% CI = -7.85 to 0.05, z = 1.93, P <
      0.05).Limited positive effects were found for the lower dosage of CEE (0.625
      mg/day) which showed a significant improvement in MMSE score only when assessed
      at two months, and disappeared after correction for multiple testing. No
      significant effects for MMSE were found at longer end points (3, 6 and 12 months
      of treatment). With a dosage of 1.25 mg/d CEE, short-term significant effects
      were found for Trial-Making test B at one month and Digit Span backward at four
      months. After two months of transdermal diestradiol (E2) treatment, a highly
      significant effect was observed for the word recall test (WMD = 6.50, 95% CI =
      4.04 to 8.96, z = 5.19, P < 0.0001). No other significant effects were found for
      other outcomes measured. AUTHORS' CONCLUSIONS: Currently, HRT or ERT for
      cognitive improvement or maintenance is not indicated for women with AD.

PMID- 19160225
TI  - Interventions for replacing missing teeth: different times for loading dental
      implants.
AB  - BACKGROUND: To minimize the risk of implant failure, osseointegrated dental
      implants are conventionally kept load-free during the healing period. During
      healing removable prostheses are used, however many patients find these temporary
      prostheses rather uncomfortable and it would be beneficial if the healing period
      could be shortened without jeopardizing implant success. Nowadays immediately and
      early loaded implants are commonly used in mandibles (lower jaws) of good bone
      quality. It would be useful to know whether there is a difference in success
      rates between immediately or early loaded implants compared with conventionally
      loaded implants. OBJECTIVES: To evaluate the efficacy of (1) immediate (within 1
      week), early (between 1 week and 2 months), and conventional (after 2 months)
      loading of osseointegrated implants, and of (2) immediate occlusal versus non
      occlusal loading during the bone healing phase. SEARCH STRATEGY: The Cochrane
      Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE were searched.
      Handsearching included several dental journals. Authors of all identified trials,
      an Internet discussion group and 55 dental implant manufacturers were contacted
      to find unpublished randomised controlled trials (RCTs). The last electronic
      search was conducted on 4 June 2008. SELECTION CRITERIA: All RCTs of root-form
      osseointegrated dental implants, having a follow up of 4 months to 1 year,
      comparing the same implant type immediately, early and conventionally loaded or
      occlusally and non-occlusally loaded. Outcome measures were: prosthesis and
      implant failures and radiographic marginal bone level changes. DATA COLLECTION
      AND ANALYSIS: Data were independently extracted, in duplicate, by two review
      authors. Authors were contacted for details of randomisation and withdrawals and
      a quality assessment was carried out. The Cochrane Collaboration's statistical
      guidelines were followed. MAIN RESULTS: Thirty RCTs were identified and 22 trials
      including 976 participants in total were included. Twelve trials compared
      immediate versus conventional loading, three early versus conventional loading,
      six immediate versus early loading, and one occlusally versus non-occlusally
      loaded implants. On a patient, rather than per implant basis, there were no
      statistically significant differences for any of the meta-analyses. AUTHORS'
      CONCLUSIONS: It is possible to successfully load dental implants immediately or
      early after their placement in selected patients, though not all clinicians may
      achieve optimal results. It is unclear whether it is beneficial to avoid occlusal
      contacts during the osseointegration phase. Trends suggest that immediately
      loaded implants fail more often than those conventionally loaded, but less
      commonly than those loaded early. If a clinician wishes to load the implants
      early, it might be wiser to load them immediately (within 1 week) rather than
      waiting for 1 or 2 months. A high degree of primary implant stability (high value
      of insertion torque) seems to be one of the prerequisites for a successful
      immediate/early loading procedure. More well designed RCTs are needed and should
      be reported according to the CONSORT guidelines (www.consort-statement.org/).

PMID- 19160226
TI  - Oxygen therapy for cystic fibrosis.
AB  - BACKGROUND: The most serious complications of cystic fibrosis (CF) relate to
      respiratory insufficiency. Oxygen supplementation therapy has been a standard of
      care for individuals with chronic lung diseases associated with hypoxemia for
      decades. Physicians commonly prescribe oxygen therapy for people with CF when
      hypoxemia occurs. However, it is unclear if empiric evidence is available to
      provide indications for this therapy with its financial costs and often profound
      impact on lifestyle. OBJECTIVES: To assess whether oxygen therapy improves the
      longevity or quality of life of individuals with CF. SEARCH STRATEGY: We searched
      the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register,
      comprising references identified from comprehensive electronic database searches
      and handsearches of relevant journals and abstract books of conference
      proceedings.Most recent search of Group's Trials Register: November 2008.
      SELECTION CRITERIA: Randomized or quasi-randomized controlled trials comparing
      oxygen, administered at any concentration, by any route, in people with
      documented CF for any time period. DATA COLLECTION AND ANALYSIS: Authors
      independently assessed study quality and extracted data. MAIN RESULTS: Eleven
      published studies (172 participants) are included in this review, of which only
      one examined long-term oxygen therapy (28 participants). There was no
      statistically significant improvement in survival, lung, or cardiac health. There
      was an improvement in regular attendance at school or work in those receiving
      oxygen therapy at 6 and 12 months. Four studies examined the effect of oxygen
      supplementation during sleep by polysomnography. Although oxygenation improved,
      mild hypercapnia was noted. Participants took less time to fall asleep and spent
      a reduced percentage of total sleep time in rapid eye movement sleep, but there
      were no demonstrable improvements in qualitative sleep parameters. Six studies
      evaluated oxygen supplementation during exercise. Again, oxygenation improved,
      but mild hypercapnia resulted. Participants receiving oxygen therapy were able to
      exercise for a significantly longer duration during exercise. Other exercise
      parameters were not altered by the use of oxygen. AUTHORS' CONCLUSIONS: There are
      no published data to guide the prescription of chronic oxygen supplementation to
      people with advanced lung disease due to CF. Short-term oxygen therapy during
      sleep and exercise improves oxygenation but is associated with modest and
      probably clinically inconsequential hypercapnia. There are improvements in
      exercise duration, time to fall asleep and regular attendance at school or work.
      There is a need for larger, well-designed clinical trials to assess the benefits
      of long-term oxygen therapy in people with CF administered continuously or during
      exercise or sleep or both.

PMID- 19160227
TI  - WITHDRAWN: Inhaled insulin in diabetes mellitus.
AB  - BACKGROUND: Insulin therapy often relies on multiple daily injections of insulin.
      However this is a considerable burden to many people with diabetes and adherence
      to such an insulin regimen can be difficult to maintain, hence compromising
      optimal glycaemic control. Also, short acting injected insulin is absorbed more
      slowly than insulin released by the normal pancreas in response to a meal.
      Inhaled insulin has the potential to reduce the number of injections to perhaps
      one long-acting insulin per day, and provide a closer match to the natural state,
      by more rapid absorption from the lung. OBJECTIVES: To compare the efficacy,
      adverse effects and patient acceptability of inhaled versus injected insulin.
      SEARCH STRATEGY: A sensitive search strategy for randomised controlled or cross
      over trials was combined with key terms for inhaled insulins. Databases searched
      were: The Cochrane Library, MEDLINE, PubMed, EMBASE, Science Citation Index,
      BIOSIS, Web of Science Proceedings, National Research Register UK, Current
      Controlled Trials, ClinicalTrials.gov, Conference Papers Index, LexisNexis, and
      web sites of the ADA and EASD were searched for recent meeting abstracts.
      Reference lists and journals were handsearched. There were no language
      restrictions on searching. Manufacturers of inhaled insulin were also contacted.
      Date of last search October 2002. SELECTION CRITERIA: Only randomised controlled
      trials with parallel groups or controlled cross-over trials, including type 1 or
      type 2 diabetic patients of any age treated with insulin, were considered
      eligible. The minimum trial duration considered was 10 weeks, as this is the time
      taken for glycated haemoglobin to reliably reflect changes in glycaemic control.
      DATA COLLECTION AND ANALYSIS: Trial selection and evaluation of study quality was
      performed independently by two reviewers. The quality of reporting of each trial
      was assessed according to a modification of the criteria outlined in Centre for
      Reviews and Dissemination (CRD) Report 4, Spitzer; and Jadad. MAIN RESULTS: Six
      randomised controlled trials were found and the overall number of participants
      was 1191. Three trials included patients with type 1 diabetes and three with type
      2 diabetes. Three trials had a duration of 24 weeks, and three of 12 weeks. All
      were open label. There was insufficient information to determine the study
      quality. Results for HbA1c were similar for all trials, in that all showed
      comparable glycaemic control for inhaled insulin compared to an entirely
      subcutaneous regimen. All trials that reported patient satisfaction and quality
      of life showed that these were significantly greater in the inhaled insulin
      group. Overall there was no difference in total hypoglycaemic episodes between
      the groups, but one trial showed a statistically significant increase in severe
      hypoglycaemic episodes for the inhaled insulin group. No adverse pulmonary
      effects were observed in any of the studies, but longer follow-up will be
      required to be sure that there are no adverse side-effects. Cavets include: few
      studies published in full (so quality could not be assessed), and only two
      studies used the same basal regimen in both the inhaled and injected groups.
      AUTHORS' CONCLUSIONS: Inhaled insulin taken before meals, in conjunction with an
      injected basal insulin, has been shown to maintain glycaemic control comparable
      to that of patients taking multiple daily injections. The key benefit appears to
      be that patient satisfaction and quality of life are significantly improved,
      presumably due to the reduced number of daily injections required. However, the
      patient satisfaction data is based on five trials, of which only two have been
      published in full; also the three trials containing quality of life data are all
      only published in abstract form at present. In addition, longer term pulmonary
      safety data are still needed. Also, the lower bioavailability, and hence higher
      doses of inhaled insulin required, may make it less cost-effective than injected
      insulin.

PMID- 19160228
TI  - Relapse prevention interventions for smoking cessation.
AB  - BACKGROUND: A number of treatments can help smokers make a successful quit
      attempt, but many initially successful quitters relapse over time. Several
      interventions were proposed to help prevent relapse. OBJECTIVES: To assess
      whether specific interventions for relapse prevention reduce the proportion of
      recent quitters who return to smoking. SEARCH STRATEGY: We searched the Cochrane
      Tobacco Addiction Group trials register in August 2008 for studies mentioning
      relapse prevention or maintenance in title, abstracts or keywords. SELECTION
      CRITERIA: Randomized or quasi-randomized controlled trials of relapse prevention
      interventions with a minimum follow up of six months. We included smokers who
      quit on their own, or were undergoing enforced abstinence, or who were
      participating in treatment programmes. We included trials that compared relapse
      prevention interventions to a no intervention control, or that compared a
      cessation programme with additional relapse prevention components to a cessation
      programme alone. DATA COLLECTION AND ANALYSIS: Studies were screened and data
      extracted by one author and checked by a second. Disagreements were resolved by
      discussion or referral to a third author. MAIN RESULTS: Fifty-four studies met
      inclusion criteria, but were heterogeneous in terms of populations and
      interventions. We considered 36 studies that randomized abstainers separately
      from studies that randomized participants prior to their quit date.Looking at
      studies of behavioural interventions which randomised abstainers, we detected no
      benefit of brief and 'skills-based' relapse prevention methods for women who had
      quit smoking due to pregnancy, or for smokers undergoing a period of enforced
      abstinence during hospitalisation or military training. We also failed to detect
      significant effects of behavioural interventions in trials in unselected groups
      of smokers who had quit on their own or with a formal programme. Amongst trials
      randomising smokers prior to their quit date and evaluating the effect of
      additional relapse prevention components we also found no evidence of benefit of
      behavioural interventions in any subgroup. Overall, providing training in skills
      thought to be needed for relapse avoidance did not reduce relapse, but most
      studies did not use experimental designs best suited to the task, and had limited
      power to detect expected small differences between interventions. For
      pharmacological interventions, extended treatment with varenicline significantly
      reduced relapse in one trial (risk ratio 1.18, 95% confidence interval 1.03 to
      1.36). Pooling of five studies of extended treatment with bupropion failed to
      detect a significant effect (risk ratio 1.17; 95% confidence interval 0.99 to
      1.39). Two small trials of oral nicotine replacement treatment (NRT) failed to
      detect an effect but treatment compliance was low and in two other trials of oral
      NRT randomizing short-term abstainers there was a significant effect of
      intervention. AUTHORS' CONCLUSIONS: At the moment there is insufficient evidence
      to support the use of any specific behavioural intervention for helping smokers
      who have successfully quit for a short time to avoid relapse. The verdict is
      strongest for interventions focusing on identifying and resolving tempting
      situations, as most studies were concerned with these. There is little research
      available regarding other behavioural approaches. Extended treatment with
      varenicline may prevent relapse. Extended treatment with bupropion is unlikely to
      have a clinically important effect. Studies of extended treatment with nicotine
      replacement are needed.

PMID- 19160229
TI  - Intrarectal quinine versus intravenous or intramuscular quinine for treating
      Plasmodium falciparum malaria.
AB  - BACKGROUND: In children with falciparum malaria, a proprietary quinine
      preparation (adjusted to make it less acidic) administered rectally may be easier
      to use and less painful than intramuscular or intravenous administration.
      However, rectal quinine may be less effective. OBJECTIVES: To compare intrarectal
      quinine with intravenous or intramuscular quinine for treating malaria caused by
      Plasmodium falciparum. SEARCH STRATEGY: In May 2008, we searched the Cochrane
      Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library
      2008, Issue 2), MEDLINE, EMBASE, LILACS, and CINAHL. We also searched conference
      proceedings, contacted individual researchers and a pharmaceutical company, and
      checked reference lists. SELECTION CRITERIA: Randomized and quasi-randomized
      controlled trials comparing intrarectal quinine with intramuscular and
      intravenous quinine for treating people with uncomplicated and severe Plasmodium
      falciparum malaria. DATA COLLECTION AND ANALYSIS: We independently assessed each
      trial's risk of bias quality and extracted data, including adverse event data. We
      analysed dichotomous data using the odds ratio and continuous data using the mean
      difference. MAIN RESULTS: Ten randomized controlled trials, all involving
      children only (total of 1417 children), fulfilled the inclusion criteria. The
      same investigator was involved in nine of the trials. Seven trials compared
      proprietary intrarectal with intravenous quinine, and seven trials compared it
      with intramuscular treatment. We detected no statistically significant difference
      between intrarectal and intravenous or intramuscular routes for death, parasite
      clearance by 48 hours and seven days, parasite clearance time, fever clearance
      time, coma recovery time, duration of hospitalization, and time to drinking. The
      trials reporting on these outcomes were small, which resulted in large confidence
      intervals for all outcomes apart from duration of hospitalization. One large
      trial (898 children) reported that intrarectal was less painful than
      intramuscular administration. AUTHORS' CONCLUSIONS: We detected no difference in
      the effect on parasites and clinical illness for intrarectal quinine, but most
      trials were small. Pain may be less with intrarectal proprietary, buffered
      quinine preparations (made less acidic by adjustment of the pH to 4.5). Further
      larger trials in patients with severe malaria and in adults are required before
      the intrarectal route can be recommended.

PMID- 19160230
TI  - Postnatal parental education for optimizing infant general health and parent
      infant relationships.
AB  - BACKGROUND: Many learning needs arise in the early postpartum period and it is
      important to examine interventions being used to educate new parents about caring
      for themselves and their newborns during this time. OBJECTIVES: To assess the
      effects of structured postnatal education delivered by an educator to an
      individual or group on maternal/paternal and infant outcomes and health services,
      and whether the effects of structured postnatal education vary by length or type
      of intervention and by population. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (November 2007), MEDLINE (1950
      to September 2007), CINAHL (1982 to September 2007), ERIC (1966 to September
      2007), HealthSTAR (1966 to September 2007), PsycINFO (1806 to September 2007),
      Sociological Abstracts (1974 to September 2007), ClinicalTrials.gov (August
      2007), Current Controlled Trials (August 2007), Trialscentral.org (August 2007)
      and The National Research Register (August 2007). SELECTION CRITERIA: We included
      randomized controlled trials of any structured postnatal education provided by an
      educator to individual parents or groups of parents within the first two months
      post birth related to the care of an infant or of the family. We excluded studies
      of educational interventions for parents of infants in neonatal intensive care
      units. DATA COLLECTION AND ANALYSIS: Both authors assessed trial quality and
      extracted data from published reports. MAIN RESULTS: We included 14 trials (2934
      women) and excluded 24. Of the 14 included studies, education tested included:
      four on infant sleep enhancement, four on infant behaviour, two on general post
      birth health, three on infant safety, and one on father involvement/skills with
      infants. Details of the randomization procedures, allocation concealment,
      blinding of outcome assessors, and/or participant accrual/loss were often not
      reported. Of the outcomes analyzed, only five were measured similarly enough by
      more than one study to be combined in meta-analyses and these included the same
      two studies. Of these five meta-analyses, only one was found to have a low enough
      level of heterogeneity to provide an overall estimate of effect; education on
      sleep enhancement resulted in a mean difference of 29 more minutes of sleep in 24
      hours (95% confidence interval 18.53 to 39.73) than usual care. AUTHORS'
      CONCLUSIONS: The benefits of educational programs to participants and their
      newborn infants remain unclear. Education on sleep enhancement appears to
      increase infant sleep although more and larger studies are needed to confirm
      this.

PMID- 19160231
TI  - Anticholinergics for urinary symptoms in multiple sclerosis.
AB  - BACKGROUND: Multiple Sclerosis (MS) is the commonest physically disabling chronic
      neurological disease affecting young people. Urinary symptoms are present in
      about 68% of people with MS but their basis has a number of potential aetiologies
      that can change with time. OBJECTIVES: To assess the absolute and comparative
      efficacy, tolerability and safety of anticholinergic agents in MS patients.
      SEARCH STRATEGY: We searched the Cochrane Multiple Sclerosis Group Specialised
      Trials Register, the Cochrane Central Register of Controlled Trials (The Cochrane
      Library 2008, Issue1), MEDLINE (January 1966 to January 2008), EMBASE (January
      1974 to January 2008), supplemented with search of reference lists, personal
      communication with authors and relevant drug manufacturers. SELECTION CRITERIA:
      Randomised trials and cross-over trials (blinded and unblinded) that are either
      placebo-controlled or comparing two or more treatments. DATA COLLECTION AND
      ANALYSIS: All four review authors independently assessed eligibility and trial
      quality, and extracted data. Data were processed as described in the Cochrane
      Handbook for Systematic Reviews of Interventions. MAIN RESULTS: Our search
      strategy identified 33 articles of which thirty were excluded. Three single
      centre trials were included. No details were given regarding randomisation and
      blinding in the first two trials but side effects were frequent with all
      treatments.The first (Hebjorn 1977) was a double blind randomised crossover
      trial. Thirty four persons with MS received three drugs Methantheline Bromide,
      Flavoxate Chloride and Meladrazine Tartrate each for 14 days, washout periods
      were not mentioned. Median volume measurements at the first bladder contraction
      were statistically significant at a 5% level for Methantheline Bromide only
      compared to no treatment.The second (Gajewski 1986) was a prospective parallel
      group randomised study. Thirty four persons with MS were treated for 6-8 weeks
      with Oxybutynin (19 subjects) or Propantheline (15 subjects). For frequency,
      nocturia, urgency, and urge incontinence differences in symptom grade in favour
      of Oxybutynin were found. However, only for frequency the difference was
      statistically significant at 5% level.The third (Fader 2007) was a double blind
      crossover trial. Sixty four persons with MS received oral Oxybutynin or
      intravesical Atropine for 14 days. Details of randomisation and blinding were
      given. There was no significant difference between the two treatments in any
      efficacy outcome measure. Side effects and QOL scores showed significant
      differences in favour of atropine. AUTHORS' CONCLUSIONS: From the available
      evidence we cannot advocate the use of anticholinergics in MS.

PMID- 19160232
TI  - Single dose oral naproxen and naproxen sodium for acute postoperative pain in
      adults.
AB  - BACKGROUND: Naproxen, a non-steroidal anti-inflammatory drug, is used to treat
      various painful conditions including postoperative pain, and is often
      administered as the sodium salt to improve its solubility. This review updates a
      2004 Cochrane review showing that naproxen sodium 550 mg (equivalent to naproxen
      500 mg) was effective for treating postoperative pain. New studies have since
      been published. OBJECTIVES: To assess efficacy, duration of action, and
      associated adverse events of single dose oral naproxen or naproxen sodium in
      acute postoperative pain in adults. SEARCH STRATEGY: We searched Cochrane
      CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to
      October 2008. SELECTION CRITERIA: Randomised, double blind, placebo-controlled
      trials of single dose orally administered naproxen or naproxen sodium in adults
      with moderate to severe acute postoperative pain. DATA COLLECTION AND ANALYSIS:
      Two review authors independently assessed trial quality and extracted data. Pain
      relief or pain intensity data were extracted and converted into the dichotomous
      outcome of number of participants with at least 50% pain relief over four to six
      hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were
      calculated. Numbers of participants using rescue medication over specified time
      periods, and time to use of rescue medication, were sought as additional measures
      of efficacy. Information on adverse events and withdrawals were collected. MAIN
      RESULTS: The original review included 10 studies with 996 participants. This
      updated review included 15 studies (1509 participants); 11 assessed naproxen
      sodium and four naproxen. In nine studies (784 participants) using 500/550 mg
      naproxen or naproxen sodium the NNT for at least 50% pain relief over four to six
      hours was 2.7 (95% CI 2.3 to 3.2). No dose response was demonstrated over the
      range 200/220 mg to 500/550 mg, but limited data was identified. Median time to
      use of rescue medication was 8.9 hours for naproxen 500/550 mg and 2.0 hours for
      placebo. Use of rescue medication was significantly less common with naproxen
      than placebo. Associated adverse events were generally of mild to moderate
      severity and rarely led to withdrawal. AUTHORS' CONCLUSIONS: Doses equivalent to
      500 mg and 400 mg naproxen administered orally provided effective analgesia to
      adults with moderate to severe acute postoperative pain. About half of
      participants treated with these doses experienced clinically useful levels of
      pain relief, compared to 15% with placebo, and half required additional
      medication within nine hours, compared to two hours with placebo. Associated
      adverse events did not differ from placebo.

PMID- 19160233
TI  - Rehabilitation for older people in long-term care.
AB  - BACKGROUND: Examination of demographic trends indicates that the worldwide
      population is progressively ageing. It is expected that such longevity will be
      associated with an increase in morbidity and demand for long-term residential
      care. This review examines whether there is evidence that physical rehabilitation
      benefits older people in long-term care. OBJECTIVES: To evaluate physical
      rehabilitation interventions directed at improving physical function among older
      people in long-term care. SEARCH STRATEGY: We searched the trials registers of
      the following Cochrane entities: Stroke Group (searched March 2008), Effective
      Practice and Organisation of Care Group (searched August 2006) and the
      Rehabilitation and Related Therapies Field, (searched August 2006). In addition,
      we searched 17 relevant electronic databases including the Cochrane Central
      Register of Controlled Trials (The Cochrane Library 2007, Issue 3), MEDLINE (1966
      to 1 October 2007), EMBASE (1980 to 1 October 2007), CINAHL (1982 to 1 October
      2007), AMED (1985 to 1 October 2007), PsycINFO (1967 to 1 October 2007) and PEDro
      (searched 1 October 2007). We also searched trials and research registers and
      conference proceedings, checked reference lists, and contacted authors and
      researchers in the field and other relevant Cochrane entities. SELECTION
      CRITERIA: Randomised studies comparing a rehabilitation intervention designed to
      maintain or improve physical function with either no intervention or an
      alternative intervention in older people aged 60 years or over who have permanent
      long-term care residency. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trial quality and extracted data. We contacted study authors for
      additional information. MAIN RESULTS: Forty-nine trials involving 3611
      participants were included. On average, 74 (range 12 to 468) participants were
      randomised into trials at baseline. Of studies which reported age, the overall
      mean age was 82 years (range of 69 to 89). Most interventions lasted less than 20
      weeks, and comprised approximately three 30 to 45-minute group sessions per week.
      Twelve trials conducted post-intervention follow up (maximum one year). Most
      often a 'usual care' control group was used, but social activity and alternative
      interventions also featured. The primary outcome, daily activity restriction, was
      reported by 38 trials. A range of secondary outcomes are also reported. AUTHORS'
      CONCLUSIONS: Provision of physical rehabilitation interventions to long-term care
      residents is worthwhile and safe, reducing disability with few adverse
      events.Most trials reported improvement in physical condition. However, there is
      insufficient evidence to make recommendations about the best intervention,
      improvement sustainability and cost-effectiveness.

PMID- 19160234
TI  - Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or
      pelvic surgery.
AB  - BACKGROUND: Major abdominal and pelvic surgery carries a high risk of venous
      thromboembolism (VTE). The efficacy of thromboprophylaxis with low-molecular
      weight heparin (LMWH) administered during the in-hospital period is well
      documented, but the optimal duration of thromboprophylaxis after surgery remains
      controversial. Some studies suggest that patients undergoing major abdominal
      surgery benefit from prolongation of the thromboprophylaxis to 1 month after
      surgery. No systematic review on prolonged thromboprophylaxis after major
      abdominal or pelvic surgery has been published. OBJECTIVES: To evaluate the
      efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 1
      month after abdominal or pelvic surgery with thromboprophylaxis administered
      during the in-hospital period only in preventing late VTE. SEARCH STRATEGY:
      Electronic searches were performed January 2008 in the Medline, Embase, Lilacs,
      and the Cochrane Central Register of Controlled Trials. Abstract books from major
      congresses addressing thromboembolism were hand searched, as were reference lists
      from studies of relevance. SELECTION CRITERIA: We assessed both randomised and
      non-randomised controlled clinical trials comparing prolonged thromboprophylaxis
      with any anti-thrombotic agent with placebo and/or thromboprophylaxis during the
      admission period only. The patient population in the trials were patients
      undergoing abdominal or pelvic surgery. The outcome measures included VTE (deep
      venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective
      means (ascending bilateral venography, ultrasonography, pulmonary
      ventilation/perfusion scintigraphy, spiral CT scan or autopsy). Studies
      exclusively reporting on clinical diagnosis of VTE, without objective
      confirmation were excluded. DATA COLLECTION AND ANALYSIS: The identification of
      studies and data extraction were performed by the authors. Outcomes were VTE (DVT
      or PE) assessed by objective means. Safety outcome were defined as bleeding
      complications and mortality within 3 months after surgery. MAIN RESULTS: The
      search exclusively detected trials evaluating prolonged thromboprophylaxis with
      LMWH as compared to control or placebo. 133 studies were found in the searches,
      of which only 4 were found eligible for inclusion, and 129 were excluded. The
      incidence of overall VTE after major abdominal or pelvic surgery was 14.3% (95%
      confidence interval 11.2% - 17.8%) in the control group as compared to 6.1% (95%
      CI 4.0% - 8.7%) in the patients receiving out-of-hospital LMWH. This difference
      was statistically significant, Peto Odds Ratio 0.41 (95% CI 0.26 -0.63), P <
      0.0005. Prolonged thromboprophylaxis with LMWH was also associated with a
      statistically significant reduction of even the incidence of symptomatic VTE from
      1.7% (95% CI 0.8% - 3.4%) in the control group to 0.2 % (95% CI 0.0% - 1.2%) in
      patients receiving prolonged thromboprophylaxis, Peto Odds ratio 0.22 (95% CI
      0.06 -0.80), P = 0.02. The respective incidence of bleeding in the control and
      LMWH group were 3.7% (95% CI 2.4% -5.5%) and 4.1% (95% CI 2.7% - 6.0%), Peto Odds
      ratio 1.11 (95% CI 0.62 - 1.97), P = 0.73. There was no significant heterogeneity
      detected as regards to outcome parameters reported in the included trials.
      AUTHORS' CONCLUSIONS: Prolonged thromboprophylaxis with LMWH significantly
      reduces the risk of VTE compared to thromboprophylaxis during hospital admittance
      only, without increasing bleeding complications after major abdominal or pelvic
      surgery.

PMID- 19160235
TI  - WITHDRAWN: Bioresorbable fixation devices for musculoskeletal injuries in adults.
AB  - BACKGROUND: Bioresorbable implants for musculoskeletal injuries involving bone
      and ligaments in adults might have significant advantages compared to the
      conventionally used non-resorbable metal implants because they lead to a gradual
      transfer of the mechanical load from the implant to the healing bone and do not
      require a secondary removal operation. Tissue reactions may present a problem and
      bioresorbable screws are mechanically not as strong as their metal counterparts.
      OBJECTIVES: To compare bioresorbable implants to non-resorbable implants with
      respect to functional outcome, wound infections, other complications and
      reoperation rate,in the fixation of bone fractures or re-attachment of soft
      tissue to bone. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle
      Trauma Group Specialised Register (March 2004), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to February
      2004), EMBASE (1988 to February 2004), BL Inside (to February 2004), SIGLE (to
      February 2004), the metaRegister of Controlled Trials at http//:controlled
      trials.com/, and reference lists of articles. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) and quasi-randomised trials, comparing bioresorbable
      osteosynthesis with metal osteosynthesis (including titanium and stainless steel
      implants) were included. DATA COLLECTION AND ANALYSIS: Review authors
      independently assessed trial quality and extracted data. Data were pooled where
      relevant and possible. Sub-analyses for specific type of fractures and for
      specific type of tissue reactions were performed. Requests for more information
      were sent to trialists. MAIN RESULTS: No significant difference between the
      bioresorbable and other implants could be demonstrated with respect to functional
      outcome, infections and other complications. Reoperation rates were lower in some
      of the groups of people treated with bioresorbable implants. AUTHORS'
      CONCLUSIONS: In a selected group of compliant patients with simple fractures, the
      use of bioresorbable fixation devices might be advantageous.

PMID- 19160236
TI  - Ear drops for the removal of ear wax.
AB  - BACKGROUND: Problems attributed to the accumulation of wax (cerumen) are among
      the most common reasons for people to present to their general practitioners with
      ear trouble. Treatment for this condition often involves use of a wax softening
      agent (cerumenolytic) to disperse the cerumen, reduce the need for, or facilitate
      syringing, but there is no consensus on the effectiveness of the variety of
      cerumenolytics in use. OBJECTIVES: To assess the effectiveness of ear drops
      (cerumenolytics) for the removal of symptomatic ear wax. SEARCH STRATEGY: We
      searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library,
      2008 issue 2); MEDLINE; EMBASE; CINAHL; ISI Proceedings; Cambridge Scientific
      Abstracts; mRCT and additional sources for published and unpublished trials. The
      date of the most recent search was April 2008. SELECTION CRITERIA: We identified
      all randomised controlled trials in which a cerumenolytic was compared with no
      treatment, a placebo, or other cerumenolytics in participants with obstructing or
      impacted ear wax, and in which the proportion of participants with sufficient
      clearance of the external canal to make further mechanical clearance unnecessary
      (primary outcome measure) was stated or calculable. DATA COLLECTION AND ANALYSIS:
      The two authors reviewed all the retrieved trials and applied the inclusion
      criteria independently. MAIN RESULTS: Nine trials satisfied the inclusion
      criteria. In all, 679 participants received one of 11 different cerumenolytics.
      One trial compared active treatments with no treatment, three compared active
      treatments with water or a saline 'placebo', and all nine trials compared two or
      more active treatments. Eight trials included syringing as a secondary
      intervention.Overall, results were inconclusive. The majority of comparisons
      showed no difference between treatments. Meta-analysis of two high quality trials
      produced a statistical difference in favour of triethanolamine polypeptide over
      saline in preventing the need for syringing, but no other significant differences
      between treatments.In three trials of high to moderate quality, no difference was
      found between the effectiveness of either sodium bicarbonate ear drops,
      chlorbutanol, triethanolamine polypeptide oleate condensate or docusate sodium
      liquid versus a sterile water or saline 'placebo'.One trial of moderate
      methodological quality found all three treatments - sodium bicarbonate ear drops,
      chlorbutanol and sterile water - to be significantly better than no treatment at
      preventing the need for syringing.None of the higher quality trials demonstrated
      superiority of one agent over another in direct comparisons. AUTHORS'
      CONCLUSIONS: Trials have been heterogeneous and generally of low or moderate
      quality, making it difficult to offer any definitive recommendations on the
      effectiveness of cerumenolytics for the removal of symptomatic ear wax. Using
      drops of any sort appears to be better than no treatment, but it is uncertain if
      one type of drop is any better than another. Future trials should be of high
      methodological quality, have large sample sizes, and compare both oil-based and
      water-based solvents with placebo, no treatment or both.

PMID- 19160237
TI  - Olanzapine in long-term treatment for bipolar disorder.
AB  - BACKGROUND: Many patients with bipolar disorder require long-term treatment to
      prevent recurrence. Antipsychotic drugs are often used to treat acute manic
      episodes. It is important to clarify whether olanzapine could have a role in long
      term prevention of manic and depressive relapses. OBJECTIVES: To assess the
      effects of olanzapine, as monotherapy or adjunctive treatment, in preventing
      manic, depressive and mixed episodes in patients with bipolar affective disorder.
      SEARCH STRATEGY: We searched the Cochrane Collaboration Depression, Anxiety and
      Neurosis Controlled Trials Register (September 2006), the Cochrane Central
      Register of Controlled Trials (September 2006), MEDLINE (1966-December 2007),
      EMBASE (1980-2006), CINAHL (1982-2006), PsycINFO (1872-2006) and reference lists.
      We also contacted experts, trialists and pharmaceutical companies in the field.
      SELECTION CRITERIA: Randomised controlled trials comparing olanzapine with
      placebo or other active treatment in long-term treatment of bipolar disorder.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial
      quality and extracted data. We contacted study authors for additional
      information. MAIN RESULTS: Five trials (1165 participants) were included in the
      review. There was no statistically significant difference between olanzapine and
      placebo (either alone or in combination with lithium or valproate) in terms of
      number of participants who experienced relapse into mood episode (random effects
      RR 0.68, 95% CI 0.43 to 1.07, p = 0.09; 2 studies, n=460), however restricting
      the analysis to the trial that compared olanzapine monotherapy versus placebo,
      there was a statistically significant difference in favour of olanzapine (RR
      0.58, 95% CI 0.49 to 0.69, p<0.00001). No statistically significant difference
      was found between olanzapine and other mood stabilisers (lithium or valproate) in
      preventing symptomatic relapse for any mood episode, however, olanzapine was more
      effective than lithium in preventing symptomatic manic relapse (RR 0.59, 95% CI
      0.39 to 0.89, p = 0.01; 1 study, n=361). Olanzapine either alone or as adjunctive
      treatment to mood stabilisers was associated with significantly greater weight
      gain than placebo. By contrast, olanzapine was associated with a lower rate of
      manic worsening, but with a higher rate of weight increase and depression than
      lithium. AUTHORS' CONCLUSIONS: Though based on a limited amount of information,
      there is evidence that olanzapine may prevent further mood episodes in patients
      who have responded to olanzapine during an index manic or mixed episode and who
      have not previously had a satisfactory response to lithium or valproate. However,
      notwithstanding these positive results, the current evidence is stronger for
      lithium as first line maintenance treatment of bipolar disorder.

PMID- 19160238
TI  - Magnesium sulphate for women at risk of preterm birth for neuroprotection of the
      fetus.
AB  - BACKGROUND: Epidemiological and basic science evidence suggests that magnesium
      sulphate before birth may be neuroprotective for the fetus. OBJECTIVES: To assess
      the effects of magnesium sulphate as a neuroprotective agent when given to women
      considered at risk of preterm birth. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (31 August 2008). SELECTION
      CRITERIA: Randomised controlled trials of antenatal magnesium sulphate therapy in
      women threatening or likely to give birth at less than 37 weeks' gestational age.
      For one subgroup analysis, studies were broadly categorised by the primary intent
      of the study into "neuroprotective intent", or "other intent (maternal
      neuroprotective - pre-eclampsia)", or "other intent (tocolytic)". DATA COLLECTION
      AND ANALYSIS: At least two authors assessed trial eligibility and quality, and
      extracted data. MAIN RESULTS: Five trials (6145 babies) were eligible for this
      review. Antenatal magnesium sulphate therapy given to women at risk of preterm
      birth substantially reduced the risk of cerebral palsy in their child (Relative
      Risk (RR) 0.68; 95% Confidence interval (CI) 0.54 to 0.87; five trials; 6145
      infants). There was also a significant reduction in the rate of substantial gross
      motor dysfunction (RR 0.61; 95% CI 0.44 to 0.85; four trials; 5980 infants). No
      statistically significant effect of antenatal magnesium sulphate therapy was
      detected on paediatric mortality (RR 1.04; 95% CI 0.92 to 1.17; five trials; 6145
      infants), or on other neurological impairments or disabilities in the first few
      years of life. Overall there were no significant effects of antenatal magnesium
      therapy on combined rates of mortality with cerebral palsy, although there were
      significant reductions for the neuroprotective groups RR 0.85; 95% CI 0.74 to
      0.98; four trials; 4446 infants, but not for the other intent subgroups. There
      were higher rates of minor maternal side effects in the magnesium groups, but no
      significant effects on major maternal complications. AUTHORS' CONCLUSIONS: The
      neuroprotective role for antenatal magnesium sulphate therapy given to women at
      risk of preterm birth for the preterm fetus is now established. The number of
      women needed to be treated to benefit one baby by avoiding cerebral palsy is 63
      (95% confidence interval 43 to 87). Given the beneficial effects of magnesium
      sulphate on substantial gross motor function in early childhood, outcomes later
      in childhood should be evaluated to determine the presence or absence of later
      potentially important neurological effects, particularly on motor or cognitive
      function.

PMID- 19160239
TI  - Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer.
AB  - BACKGROUND: Epithelial ovarian cancer kills about 1700 in the UK each year. Ten
      to fifteen percent of all cases are diagnosed early when there is still a good
      chance of cure. The treatment of early stage disease involves surgery to remove
      disease often followed by chemotherapy. The largest clinical trials of this
      adjuvant therapy show an overall survival (OS) advantage with adjuvant platinum
      based chemotherapy but the precise role of this treatment in sub-groups of
      patients with differing prognoses needs to be defined. OBJECTIVES: To
      systematically review the evidence for adjuvant chemotherapy in early stage
      epithelial ovarian cancer to determine; firstly whether there is a survival
      advantage of this treatment over the policy of observation following surgery with
      chemotherapy reserved for treatment of disease recurrence, and secondly; to
      determine if clinical sub-groups of differing prognosis based on histological sub
      type or completeness of surgical staging, have more or less to gain from
      chemotherapy following initial surgery. SEARCH STRATEGY: An electronic search was
      performed using the Cochrane Gynaecological Cancer Specialised Register, Cochrane
      Central Register of Controlled Trials (CENTRAL, Issue 2 2008), MEDLINE (1966 to
      2008), EMBASE (1980 to 2008) and CancerLit. The search strategy was developed
      using free text and medical subject headings (MESH). This yielded a large number
      of article titles which were sifted down by two review authors to a limited
      number of articles, the full text versions of which were independently reviewed
      to select out clinical trials of direct and specific relevance to the review
      question. Hand searches of the clinical literature were conducted where
      appropriate to identify additional full-text papers or abstracts of other
      directly relevant clinical trials. SELECTION CRITERIA: The review authors
      selected those clinical trials that met the inclusion criteria set out based on
      the populations, interventions , comparisons and outcome measures as detailed in
      the full text review. DATA COLLECTION AND ANALYSIS: Two review authors
      independently extracted data and assessed trial quality. Disagreements were
      resolved by discussion or a third reviewer. Random effects meta-analyses and sub
      group analyses were conducted. MAIN RESULTS: Five randomised controlled trials
      (RCTs), enrolling 1277 women, with 46 to 110 months follow-up, met our inclusion
      criteria. These trials had low risk of bias. Meta-analysis of three trials with
      adequate data, assessing 1008 women, indicated that women who received adjuvant
      platinum-based chemotherapy had better overall survival (OS) than those who did
      not (hazard ratio (HR) 0.71; 95% CI 0.53 to 0.93). Likewise, meta-analysis of
      four trials with adequate data, assessing 1170 women, indicated that women who
      received adjuvant chemotherapy had better progression-free survival (PFS) than
      those who did not (HR 0.67; 95% CI 0.53 to 0.84). The trials included in these
      meta-analyses gave consistent estimates of the effects of chemotherapy.Sub-group
      analysis suggested that women who had optimal surgical staging of their disease
      were unlikely to benefit from adjuvant chemotherapy (HR for OS 1.22; 95% CI 0.63
      to 2.37) whereas those who had sub-optimal staging did (HR for OS 0.63; 95% CI
      0.46 to 0.85). One trial showed a benefit from adjuvant chemotherapy among women
      at high risk (HR for OS 0.48; 95% CI 0.32 to 0.72) but not among those at low
      risk (HR for OS 0.95; 95% CI 0.54 to 1.66). However, these sub-group findings
      could be due to chance. AUTHORS' CONCLUSIONS: Adjuvant platinum based
      chemotherapy is effective in prolonging the survival of the majority of patients
      who are assessed as having early stage epithelial ovarian cancer. However, even
      given the limits of sub-group analyses, there is strong evidence that optimal
      surgical staging identifies patients who have either little or nothing to gain
      from adjuvant chemotherapy. Taken together with the lack of a survival advantage
      seen in patients with "low-risk" cancers in the ICON1 trial, it appears safe to
      withhold adjuvant chemotherapy from optimally staged patients with well
      differentiated tumours.

PMID- 19160240
TI  - Street lighting for preventing road traffic injuries.
AB  - BACKGROUND: Road traffic crashes are a major cause of death and injury,
      especially in low and middle-income countries. It is estimated that road traffic
      injuries will have risen from ninth to third in world disease burden rankings by
      2020, accounting for 2.3 million deaths globally. Street lighting has been
      suggested as a relatively low cost intervention with the potential to prevent
      traffic crashes. OBJECTIVES: To assess the effects of street lighting on injuries
      caused by road traffic crashes. SEARCH STRATEGY: We searched the Cochrane
      Injuries Group's Specialised Register, CENTRAL, MEDLINE, EMBASE, TRANSPORT,
      Australian Transport Index. We also searched the Internet and checked reference
      lists of relevant papers. The search was not restricted by language or
      publication status. The searches were conducted to October 2008. SELECTION
      CRITERIA: Randomised controlled trials, non-randomised controlled trials and
      controlled before-after studies, comparing new street lighting with unlit roads,
      or improved street lighting with the pre-existing lighting level. DATA COLLECTION
      AND ANALYSIS: Two authors screened search results, extracted data, assessed risk
      of bias and analysed the data. MAIN RESULTS: We found 16 controlled before-after
      studies of street lighting, all reporting crash data, of which 14 contributed
      data to the meta-analysis. Seven trials included a designated control site, the
      other nine collected data at one site with the daytime data being used as the
      control. The methodological quality of the trials was generally poor.Three trials
      compared street lighting with an area control on total crashes; pooled rate ratio
      (RR) = 0.45 (95% Confidence Interval (CI) 0.29 to 0.69). Two trials compared
      street lighting with an area control on total injury crashes (all severities); RR
      = 0.78 (95% CI 0.63 to 0.97). No trials compared the number of fatal crashes with
      an area control.Ten trials compared street lighting with a day time control on
      total crashes; pooled RR = 0.68 (95% CI 0.56 to 0.83). Five trials compared
      street lighting with a day time control on total injury crashes; pooled RR = 0.68
      (95% CI 0.59 to 0.79). Three trials compared street lighting with a day time
      control on fatal crashes; pooled RR = 0.33 (95% CI 0.17 to 0.66). AUTHORS'
      CONCLUSIONS: The results from this systematic review suggests that street
      lighting may prevent road traffic crashes, injuries and fatalities. However,
      further well designed studies are needed to determine the effectiveness of street
      lighting in middle and low-income countries.

PMID- 19160241
TI  - Aspirin or anticoagulants for treating recurrent miscarriage in women without
      antiphospholipid syndrome.
AB  - BACKGROUND: Since hypercoagulability might result in recurrent miscarriage,
      anticoagulant agents could potentially increase the live-birth rate in subsequent
      pregnancies in women with either inherited thrombophilia or unexplained recurrent
      miscarriage. OBJECTIVES: To evaluate the efficacy and safety of anticoagulant
      agents, such as aspirin and heparin, in women with a history of at least two
      miscarriages without apparent causes other than inherited thrombophilia. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (April 2008), the Cochrane Central Register of Controlled Trials (The
      Cochrane Library 2007, Issue 1), MEDLINE (January 1966 to March 2007), and EMBASE
      (1980 to March 2007). We scanned bibliographies of all located articles for any
      unidentified articles. SELECTION CRITERIA: Randomised and quasi-randomised
      controlled trials that assessed the effect of anticoagulant treatment on the live
      birth rate in women with a history of at least two miscarriages (up to 20 weeks
      of amenorrhoea) without apparent causes other than inherited thrombophilia were
      eligible. Interventions included aspirin, unfractionated heparin, and low
      molecular weight heparin for the prevention of miscarriage. One treatment could
      be compared with another or with placebo. DATA COLLECTION AND ANALYSIS: Two
      authors assessed the trials for inclusion in the review and extracted the data.
      We double checked the data. MAIN RESULTS: Two studies (189 participants) were
      included in the review. In one study, 54 pregnant women with recurrent
      miscarriage (RM) but no detectable anticardiolipin antibodies were randomised to
      low-dose aspirin or placebo. RM was defined as three or more consecutive
      miscarriages (occurring before 22 weeks' gestational age (based on last menstrual
      period)). Similar live-birth rates were observed with aspirin and placebo, both
      81% (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.78 to 1.29). In the
      other study, 107 women with consecutive recurrent miscarriage without any
      apparent cause and no hereditary thrombophilia were randomised between enoxaparin
      and aspirin. Here RM was stated as three or more consecutive first trimester
      miscarriages or at least two consecutive second trimester miscarriages. Similar
      live birth rates were observed with enoxaparin and aspirin, respectively 82% and
      84% (RR 0.97, 95% CI 0.81 to 1.16). AUTHORS' CONCLUSIONS: There is a paucity in
      studies on the efficacy and safety of aspirin and heparin in women with a history
      of at least two miscarriages without apparent causes other than inherited
      thrombophilia. The two reviewed trials studied different treatments and only one
      study was placebo-controlled. Neither of the studies showed a benefit of one
      treatment over the other. Therefore, the use of anticoagulants in this setting is
      not recommended. However, large randomised placebo-controlled trials are still
      urgently needed.

PMID- 19160242
TI  - Pharmacological interventions for preventing complications in idiopathic
      hypercalciuria.
AB  - BACKGROUND: Idiopathic hypercalciuria is an inherited metabolic abnormality
      characterised by excessive amounts of calcium excreted into the urine in patients
      with normal serum levels of calcium. The morbidity of hypercalciuria is related
      to kidney stone disease and bone demineralization. In children, hypercalciuria
      can cause recurrent haematuria, frequency-dysuria syndrome, urinary tract
      infection and abdominal and lumbar pain. Several pharmacological treatments have
      been described that can decrease the levels of urinary calcium or its index of
      urinary crystallization. OBJECTIVES: To assess the benefits and harms of
      pharmacological interventions for preventing complications and decreasing
      urological symptoms in patients with idiopathic hypercalciuria. SEARCH STRATEGY:
      We searched MEDLINE, EMBASE, the Cochrane Renal Group's specialised register, the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library),
      handsearched relevant conference proceedings and reference lists of articles.
      SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTS that
      compared any pharmacological intervention for preventing complications in
      idiopathic hypercalciuria, with placebo, other pharmacological intervention or a
      different administration mode or dose of the same treatment given for a minimum
      duration of four months and had a follow-up period of at least six months. DATA
      COLLECTION AND ANALYSIS: Four authors assessed the studies for inclusion and
      extracted the data. Disagreements were resolved through discussion. Results were
      expressed as risk ratios (RR) with 95% confidence intervals (CI) or mean
      difference (MD). MAIN RESULTS: Five studies (316 adult patients) were included.
      Four compared thiazides with standard treatment (periodic clinical follow-up and
      increased water intake) or specific dietary recommendations and one analysed the
      effect of thiazide plus a neutral potassium salt. There was a significant
      decrease in the number of new stone recurrences in those treated with thiazides
      (RR 1.61, 95% CI 1.33 to 1.96), although the follow-up periods varied. The stone
      formation rate also showed a statistically significant decrease in the patients
      treated with diuretics (MD -0.18, 95% CI -0.30 to -0.06). Thiazides plus
      potassium salts significantly decreased calciuria and vitamin D levels. AUTHORS'
      CONCLUSIONS: There is some evidence that in patients with idiopathic
      hypercalciuria and recurrent stones, the addition of thiazides to a normal or
      modified diet for short to long periods (five months to three years) reduced the
      number of stone recurrences and decreased the stone formation rate. Thiazides and
      neutral potassium phosphate decreased calciuria in symptomatic patients with
      idiopathic hypercalciuria. There were no studies investigating the effect of
      pharmacological treatment on other clinical complications or asymptomatic
      idiopathic hypercalciuria.

PMID- 19160244
TI  - Image-guided percutaneous procedure plus metronidazole versus metronidazole alone
      for uncomplicated amoebic liver abscess.
AB  - BACKGROUND: Metronidazole is the standard of care for uncomplicated amoebic liver
      abscesses (considering that complicated liver abscesses are those localized in
      left lobe, multiple, and/or pyogenic abscesses). However, a subset of patients
      with amoebic liver abscesses remain symptomatic, with a significant risk of
      rupture of the abscess into the peritoneum. The role of image-guided percutaneous
      therapeutic aspiration in these patients remains controversial. OBJECTIVES: To
      assess the beneficial and harmful effects of image-guided percutaneous procedure
      plus metronidazole versus metronidazole alone in patients with uncomplicated
      amoebic liver abscess. SEARCH STRATEGY: We searched the Cochrane Hepato-Biliary
      Group Controlled Trials Register, the Cochrane Central Register of Controlled
      Trials in The Cochrane Library (Issue 2, 2007), MEDLINE (1966 to November 2007),
      EMBASE (1988 to September 2007), and Science Citation Index Expanded (1945 to
      September 2007). SELECTION CRITERIA: Randomised or quasi-randomised trials
      comparing an image-guided percutaneous procedure plus metronidazole versus
      metronidazole alone in patients with uncomplicated amoebic liver abscess. DATA
      COLLECTION AND ANALYSIS: Inclusion criteria, trial quality assessment, and data
      extraction were done in duplicate. We calculated relative risks (RR) and mean
      differences, and checked for heterogeneity by visual inspection of forest plots
      and chi-squared and I(2) tests. MAIN RESULTS: Seven low quality randomised trials
      were included. All studies included a total of 310 patients, but due to selective
      outcome reporting bias, less patients could be included in our analyses. Pooled
      analysis of three homogenous trials showed that needle aspiration did not
      significantly increase the proportion of patients with fever resolution (RR 0.60,
      95% confidence interval (CI) 0.22 to 1.61). Sensitivity analysis according to
      trial quality preserved these findings. Trials that evaluated resolution of
      abdominal pain, days to resolution of fever, pain, resolution of abscess
      cavities, reduction in liver size, and duration of hospitalisation were
      heterogeneous. The benefits in the number of days to resolution of pain (MD 
      1.59, 95%CI -2.73 to -0.42), number of days to resolution of abdominal tenderness
      (MD -1.70, 95%CI -2.86 to -0.54), and duration of hospitalisation (MD -1.31,
      95%CI -2.05 to -0.57) were observed in the needle aspiration group only. AUTHORS'
      CONCLUSIONS: Therapeutic aspiration in addition to metronidazole to hasten
      clinical or radiologic resolution of uncomplicated amoebic liver abscesses cannot
      be supported or refuted by the present evidence. The trials lack methodological
      rigour and adequate sample size to conclude on the presence of effectiveness of
      adjunctive image-guided aspiration plus metronidazole versus metronidazole alone.
      Further randomised trials are necessary.

PMID- 19160243
TI  - Short versus standard duration antibiotic therapy for acute streptococcal
      pharyngitis in children.
AB  - BACKGROUND: The standard duration of treatment for acute group A beta hemolytic
      streptococcus (GABHS) pharyngitis with oral penicillin is 10 days. Shorter
      duration antibiotics may have comparable efficacy. OBJECTIVES: To summarize the
      evidence regarding the efficacy of two to six days of newer oral antibiotics
      (short duration) compared to 10 days of oral penicillin (standard duration) in
      treating children with acute GABHS pharyngitis. SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2007, issue 4), which contains the Acute Respiratory Infections Group's
      Specialized Register; the Database of Abstracts of Reviews of Effects (DARE);
      MEDLINE (1966 to October 2007); OLDMEDLINE (1950 to December 1965); and EMBASE
      (January 1990 to November 2007). SELECTION CRITERIA: Randomized controlled trials
      (RCTs) comparing short duration oral antibiotics to standard duration oral
      penicillin in children aged 1 to 18 years with acute GABHS pharyngitis. DATA
      COLLECTION AND ANALYSIS: Two review authors scanned the titles and abstracts of
      retrieved citations and applied the inclusion criteria. We retrieved included
      studies in full and extracted data. Two review authors independently assessed
      trial quality. MAIN RESULTS: Twenty studies were included with 13,102 cases of
      acute GABHS pharyngitis. Compared to standard duration treatment, the short
      duration treatment had shorter periods of fever (mean difference (MD) -0.30 days,
      95% CI -0.45 to -0.14) and throat soreness (MD -0.50 days, 95% CI -0.78 to 
      0.22); lower risk of early clinical treatment failure (OR 0.80, 95% CI 0.67 to
      0.94); no significant difference in early bacteriological treatment failure (OR
      1.08, 95% CI 0.97 to 1.20), or late clinical recurrence (OR 0.95, 95% CI 0.83 to
      1.08). However, the overall risk of late bacteriological recurrence was worse in
      the short duration treatment (OR 1.31, 95% CI 1.16 to 1.48), although no
      significant differences were found when studies of low dose azithromycin
      (10mg/kg) were eliminated (OR 1.06, 95% CI 0.92 to 1.22). Three studies reported
      long duration complications with no statistically significant difference (OR
      0.53, 95% CI 0.17 to 1.64). AUTHORS' CONCLUSIONS: Three to six days of oral
      antibiotics had comparable efficacy compared to the standard duration 10 day oral
      penicillin in treating children with acute GABHS pharyngitis. In countries with
      low rates of rheumatic fever, it appears safe and efficacious to treat children
      with acute GABHS pharyngitis with short duration antibiotics. In areas where the
      prevalence of rheumatic heart disease is still high, our results must be
      interpreted with caution.

PMID- 19160245
TI  - Paracervical local anaesthesia for cervical dilatation and uterine intervention.
AB  - BACKGROUND: Cervical dilatation and uterine intervention can be performed under
      sedation, local or general anaesthesia for obstetrics and gynaecological
      conditions. Many gynaecologists use paracervical local anaesthesia (PLA) but its
      effectiveness is unclear. OBJECTIVES: To determine the effectiveness and safety
      of paracervical anaesthesia for cervical dilatation and uterine intervention when
      compared with no treatment, placebo, other methods of regional anaesthesia,
      systemic sedation and analgesia, or general anaesthesia (GA). SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2006, Issue 1), MEDLINE (1966 to January 2006), EMBASE (1980 to
      January 2006) and reference lists of articles. SELECTION CRITERIA: We included
      randomized or controlled clinical studies involving cervical dilatation and
      uterine intervention for obstetric and gynaecological conditions. DATA COLLECTION
      AND ANALYSIS: Two authors independently evaluated studies, extracted data,
      checked and entered data into Review Manager. MAIN RESULTS: We included 17
      studies involving 1855 participants. No study of PLA versus GA met our criteria;
      eight studies compared PLA versus placebo. Injection of local anaesthetic was
      slightly less painful than injection of saline placebo, a reduction of 0.87
      points (95% CI 0.14 to 1.60) on a 10-point pain scale. Compared to placebo, PLA
      reduced abdominal pain during uterine intervention equivalent to two or three
      points on a 10-point pain scale and reduced the risk of severe pain (RR 0.16, 95%
      CI 0.06 to 0.74). There was no evidence that PLA reduced pain after the uterine
      intervention and little evidence for any effect on postoperative back or shoulder
      pain. Pain reduction by PLA was not confirmed in four studies that compared PLA
      with no treatment. Three studies compared PLA with uterosacral block;
      intracervical block; and intrauterine topical anaesthesia. Two of these studies
      showed no significant difference in pain during the procedure. Compared to
      intrauterine instillation, PLA slightly reduced severe pain (from 8.3 to 7.6, on
      a 10-point pain scale), which may be negligible. This benefit appeared to be
      greater for women who required cervical dilatation. Two studies compared PLA with
      sedation. There were no statistically significant differences in pain during or
      after the procedure, postoperative analgesia requirement, adverse effects,
      patient satisfaction, and the operator's perception of analgesia. AUTHORS'
      CONCLUSIONS: No technique provided reliable pain control in the 17 included
      studies. Some studies reported that women experienced severe pain (mean scores of
      7 to 9 out of 10) during uterine intervention, irrespective of the analgesic
      technique used. We concluded that the available evidence fails to show whether
      paracervical block is inferior, equivalent or superior to alternative analgesic
      techniques, in terms of efficacy and safety, for women undergoing uterine
      interventions.

PMID- 19160246
TI  - Intra-peritoneal prophylactic agents for preventing adhesions and adhesive
      intestinal obstruction after non-gynaecological abdominal surgery.
AB  - BACKGROUND: Intra-abdominal adhesions are common and challenge patients, surgeons
      and other healthcare providers. They are potentially preventable and several
      agents that act as barriers between adjacent peritoneal surfaces have been
      evaluated for prophylaxis. Efficacy, judged by systematic reviews, has only been
      undertaken in gynaecological surgery. OBJECTIVES: To determine efficacy and
      safety of peritoneal adhesion prophylaxis on incidence, distribution and adhesion
      related intestinal obstruction after non-gynaecological surgery. SEARCH STRATEGY:
      The Cochrane Central Register of Controlled Trials, the Cochrane Colorectal
      Cancer Group specialised register, MEDLINE (1966-2008), and EMBASE (1971-2008)
      were searched. SELECTION CRITERIA: Blinded and non-blinded, randomised and quasi
      randomised clinical trials were considered. DATA COLLECTION AND ANALYSIS: Two
      authors individually conducted the searches and assessed the quality of studies
      for inclusion which were analysed using the Revman Analyses software 5.0.0
      provided by the Cochrane collaboration. Meta-analysis used a random effects
      model. MAIN RESULTS: Seven randomised trials were eligible; six compared
      hyaluronic acid/carboxymethyl membrane (HA/CMC) and one 0.5% ferric hyaluronate
      gel against controls.HA/CMC reduced the incidence of adhesions (OR 0.15 (95% CI:
      0.05, 0.43); p=0.0005) with reduced extent (WMD -25.9% (95% CI: -40.56, -11.26);
      p=0.0005) and severity. There was no reduction of intestinal obstruction needing
      surgical intervention (odds ratio: 0.84 (95% CI: 0.24, 2.7) with comparable
      overall morbidity and mortality.The study of 0.5% ferric hyaluronate gel was
      prematurely terminated and no valid conclusions could be made but there was a
      higher incidence of overall morbidity (OR 5.04; 95% CI: 1.1, 22.9) and ileus (OR:
      9.29; 95% CI: 1.57, 54.77; p=0.01). AUTHORS' CONCLUSIONS:  IMPLICATIONS FOR
      PRACTICE: There is evidence that the use of HA/CMC membrane reduces incidence,
      extent and severity of adhesions which may, theoretically, have implications in
      re-operative abdominal surgery. There is no evidence that the incidence of
      intestinal obstruction or need for operative intervention is reduced. HA/CMC
      appears to be safe but there may be a risk of leak when wrapped around an
      anastomoses. HA/CMC may be considered for intra-abdominal, adhesion prophylaxis
      at a surgeon's discretion and clinical context. IMPLICATIONS FOR RESEARCH:
      Further research is needed to explore the effectiveness of other agents in
      abdominal surgery in general. Synergism, using agents which target different
      aspects of adhesiogenesis, with exploration effectiveness in a wide range of
      emergency and elective surgery should be considered. Longer term outcomes of
      recurrent intestinal obstruction and chronic pain, identification of high risk
      groups of patients with evaluation of cost-effectiveness are required.

PMID- 19160247
TI  - Patient education for neck pain with or without radiculopathy.
AB  - BACKGROUND: Neck disorders are common, disabling, and costly. The effectiveness
      of patient education strategies is unclear. OBJECTIVES: To assess whether patient
      education strategies, either alone or in combination with other treatments, are
      of benefit for pain, function, global perceived effect, quality of life, or
      patient satisfaction, in adults with neck pain with and without radiculopathy.
      SEARCH STRATEGY: Computerized bibliographic databases were searched from their
      start up to May 31, 2008. SELECTION CRITERIA: Eligible studies were quasi or
      randomized trials (RCT) investigating the effectiveness of patient education
      strategies for neck disorder. DATA COLLECTION AND ANALYSIS: Paired independent
      review authors carried out study selection, data abstraction, and methodological
      quality assessment. Relative risk and standardized mean differences (SMD) were
      calculated. The appropriateness of combining studies was assessed on clinical and
      statistical grounds. Because of differences in intervention type or disorder, no
      studies were considered appropriate to pool. MAIN RESULTS: Of the 10 selected
      trials, two (20%) were rated high quality. Advice was assessed as follows:Eight
      trials of advice focusing on activation compared to no treatment or to various
      active treatments, including therapeutic exercise, manual therapy and cognitive
      behavioural therapy, showed either inferiority or no difference for pain,
      spanning a full range of follow-up periods and disorder types. When compared to
      rest, two trials that assessed acute whiplash-associated disorders (WAD) showed
      moderate evidence of no difference for various forms of advice focusing on
      activation. Two trials studying advice focusing on pain & stress coping skills
      found moderate evidence of no benefit for pain in chronic mechanical neck
      disorder (MND) at intermediate/long-term follow-up. One trial compared the
      effects of ' traditional neck school ' to no treatment, yielding limited evidence
      of no benefit for pain at intermediate-term follow-up in mixed
      acute/subacute/chronic neck pain. AUTHORS' CONCLUSIONS: This review has not shown
      effectiveness for educational interventions in various disorder types and follow
      up periods, including advice to activate, advice on stress coping skills, and
      'neck school'. In future research, further attention to methodological quality is
      necessary. Studies of multimodal interventions should consider study designs,
      such as factorial designs, that permit discrimination of the specific educational
      components.

PMID- 19160248
TI  - Anakinra for rheumatoid arthritis.
AB  - BACKGROUND: In the past decade, a novel class of therapies directed against
      specific cytokines implicated in the disease process of rheumatoid arthritis
      (RA), called the 'Biologics' have greatly improved and expanded treatment for RA.
      Anakinra is an interleukin-1 receptor antagonist that is currently FDA-approved
      for moderate-severe RA that has been unresponsive to initial disease-modifying
      anti-rheumatic drugs (DMARD) therapy. OBJECTIVES: To evaluate the clinical
      effectiveness and safety of anakinra in adult patients with rheumatoid arthritis.
      SEARCH STRATEGY: We searched the following electronic databases: the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1,
      2008), MEDLINE (1950 to Week 4 2008) , EMBASE (1980 to Week 5 2008), CINAHL (1982
      to November 2007) and reference lists of articles. SELECTION CRITERIA: Randomized
      controlled trials comparing anakinra alone or in combination with DMARDs or
      biologics to placebo or other DMARDs or biologics in patients >18 years old with
      rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality and extracted data. We contacted study
      authors for additional information. MAIN RESULTS: Five trials involving 2876
      patients, 781 randomized to placebo and 2065 to anakinra, were included. There
      was a significant improvement in number of participants achieving ACR20 (38%
      versus 23%) who were treated with anakinra 50 to 150 mg daily versus placebo
      after 24 weeks. This 15% increase in patients achieving ACR20 with anakinra
      versus placebo is felt to be a clinically meaningful, though modest, outcome.
      Other efficacy data - including ACR50 (18% versus 7%), ACR70 (7% versus 2%), HAQ,
      visual analog score (VAS), Larsen radiographic scores, and change in erythrocyte
      sedimentation rate (ESR) - all demonstrated significant improvement with anakinra
      50 to 150 mg daily versus placebo as well. There were no statistically
      significant differences noted in most safety outcomes with treatment with
      anakinra versus placebo - including number of withdrawals, deaths, adverse events
      (total and serious), and infections (total and serious). Injection site reactions
      were significantly increased, occurring in 1235/1729 (71%) versus 204/729 (28%)
      of patients treated with anakinra versus placebo, respectively. The incidence of
      serious infections was clinically higher, but not statistically different, in the
      anakinra (25/1366 patients, 1.8%) versus placebo group (3/534 patients, 0.6%).
      AUTHORS' CONCLUSIONS: Anakinra is a relatively safe and modestly efficacious
      biologic therapy for rheumatoid arthritis. Although head to head comparison
      trials have not been carried out, the amount of improvement is notably less when
      compared to studies using other biologic therapies. More studies are needed to
      evaluate safety and efficacy, especially in comparison to other therapies, and
      adverse event data for the long-term use of Anakinra has yet to be assessed.

PMID- 19160249
TI  - Individual patient education for people with type 2 diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes is a common and costly chronic disease which is
      associated with significant premature mortality and morbidity. Although patient
      education is an integral component of diabetes care, there remain uncertainties
      regarding the effectiveness of different methods and modes of education.
      OBJECTIVES: To evaluate the effectiveness of individual patient education on
      metabolic control, diabetes knowledge and psychosocial outcomes. SEARCH STRATEGY:
      Multiple electronic bibliographic databases were searched, including The Cochrane
      Library, MEDLINE, Premedline, ERIC, Biosis, AMED, Psychinfo, EMBASE, CINAHL,
      APAIS-health, Australian Medical Index, Web of Science, dissertation abstracts
      and Biomed Central. SELECTION CRITERIA: Randomized controlled and controlled
      clinical trials which evaluated individual education for adults with type 2
      diabetes. The intervention was individual face-to-face patient education while
      control individuals received usual care, routine treatment or group education.
      Only studies that assessed outcome measures at least six months from baseline
      were included. DATA COLLECTION AND ANALYSIS: Information was extracted by two
      reviewers who summarized both study characteristics and outcome statistics. A
      meta-analysis using a fixed-effect model was performed if there were adequate
      studies with a specified outcome of sufficient homogeneity. For outcomes where
      there were too few studies or the assessment measurements were not standardized
      or variable, the results were summarised qualitatively. MAIN RESULTS: Nine
      studies involving 1359 participants met the inclusion criteria. Six studies
      compared individual education to usual care and three compared individual
      education to group education (361 participants). There were no long-term studies
      and overall the quality of the studies was not high. In the six studies comparing
      individual face-to-face education to usual care, individual education did not
      significantly improve glycaemic control (weighted mean difference (WMD) in HbA1c 
      0.1% (95% confidence interval (CI) -0.3 to 0.1, P = 0.33) over a 12 to 18 month
      period. However, there did appear to be a significant benefit of individual
      education on glycaemic control in a subgroup analysis of three studies involving
      participants with a higher mean baseline HbA1c greater than 8% (WMD -0.3% (95% CI
      -0.5 to -0.1, P = 0.007). In the two studies comparing individual to group
      education, there was no significant difference in glycaemic control between
      individual or group education at 12 to 18 months with a WMD in HbA1c of 0.03%
      (95% CI -0.02 to 0.1, P = 0.22). There was no significant difference in the
      impact of individual versus usual care or group education on body mass index
      systolic or diastolic blood pressure. There were too few studies to perform a
      meta-analysis on the effect of individual education on dietary self management,
      diabetes knowledge, psychosocial outcomes and smoking habits. No data were
      available on the other main outcome measures of diabetes complications or health
      service utilization and cost analysis in these studies. AUTHORS' CONCLUSIONS:
      This systematic review suggests a benefit of individual education on glycaemic
      control when compared with usual care in a subgroup of those with a baseline
      HbA1c greater than 8%. However, overall there did not appear to be a significant
      difference between individual education and usual care. In the small number of
      studies comparing group and individual education, there was an equal impact on
      HbA1c at 12 to 18 months. Additional studies are needed to delineate these
      findings further.

PMID- 19160250
TI  - Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Pulmonary rehabilitation has become a cornerstone in the management
      of patients with stable Chronic Obstructive Pulmonary Disease (COPD). Systematic
      reviews have shown large and important clinical effects of pulmonary
      rehabilitation in these patients. In unstable COPD patients who have suffered
      from an exacerbation recently, however, the effects of pulmonary rehabilitation
      are less established. OBJECTIVES: To assess the effects of pulmonary
      rehabilitation after COPD exacerbations on future hospital admissions (primary
      outcome) and other patient-important outcomes (mortality, health-related quality
      of life and exercise capacity). SEARCH STRATEGY: Trials were identified from
      searches of CENTRAL, MEDLINE, EMBASE, PEDRO and the Cochrane Central Register of
      Controlled Trials. Searches were current as of July 2008. SELECTION CRITERIA:
      Randomized controlled trials comparing pulmonary rehabilitation of any duration
      after exacerbation of COPD with conventional care. Pulmonary rehabilitation
      programmes needed to include at least physical exercise. Control groups received
      conventional community care without rehabilitation. DATA COLLECTION AND ANALYSIS:
      We calculated pooled odds ratios and weighted mean differences (WMD) using fixed
      effects models. We requested missing data from the authors of the primary
      studies. MAIN RESULTS: We identified six trials including 219 patients. Pulmonary
      rehabilitation significantly reduced hospital admissions (pooled odds ratio 0.13
      [95% CI 0.04 to 0.35], number needed to treat (NNT) 3 [95% CI 2 to 4], over 34
      weeks) and mortality (pooled odds ratio 0.29 [95% CI 0.10 to 0.84], NNT 6 [95% CI
      5 to 30] over 107 weeks). Effects of pulmonary rehabilitation on health-related
      quality of life were well above the minimal important difference (weighted mean
      differences for dyspnea, fatigue, emotional function and mastery domains of the
      Chronic Respiratory Questionnaire between 1.15 (95% CI: 0.94, 1.36) and 1.88 (95%
      CI:1.67, 2.09) and between -9.9 (95% CI:-18.05, -1.73) and -17.1 (95% CI: -23.55,
      -10.68) for total, impact and activity limitation domains of the St. Georges
      Respiratory Questionnaire). In all trials, pulmonary rehabilitation improved
      exercise capacity (60-215 meters in six-minute or shuttle walk tests). No adverse
      events were reported (two studies). AUTHORS' CONCLUSIONS: Evidence from small
      studies of moderate methodological quality suggests that pulmonary rehabilitation
      is a highly effective and safe intervention to reduce hospital admissions and
      mortality and to improve health-related quality of life in COPD patients after
      suffering an exacerbation.

PMID- 19160251
TI  - Interventions for increasing the proportion of health professionals practising in
      rural and other underserved areas.
AB  - BACKGROUND: The inequitable distribution of health professionals, within and
      between countries, poses an important obstacle to the achievement of optimal
      attainable health for all. OBJECTIVES: To assess the effectiveness of
      interventions aimed at increasing the proportion of health professionals working
      in rural and other underserved areas. SEARCH STRATEGY: We searched the
      specialised register of the Cochrane Effective Practice and Organisation of Care
      Group (up to July 2007), the Cochrane Central Register of Controlled Trials
      (CENTRAL) and the Database of Abstracts of Reviews of Effectiveness (up to July
      2007), MEDLINE (1966 to July 2007), EMBASE (1988 to July 2007), CINAHL (1982 to
      July 2007) and LILACS (up to July 2007). We also searched reference lists of all
      papers and relevant reviews identified, and contacted authors of relevant papers
      regarding any further published or unpublished work. SELECTION CRITERIA:
      Randomised controlled trials, controlled trials (not strictly randomised),
      controlled before-after studies and interrupted time series studies evaluating
      the effects of various interventions (e.g. educational, financial or regulatory
      strategies) on the recruitment and/or retention of health professionals in under
      served areas. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened
      titles and abstracts obtained from the search in order to identify potentially
      relevant studies. MAIN RESULTS: No studies met the inclusion criteria. AUTHORS'
      CONCLUSIONS: There are no studies in which bias and confounding are minimised to
      support any of the interventions that have been implemented to address the
      inequitable distribution of health care professionals. Well-designed studies are
      needed to confirm or refute findings of various observational studies regarding
      educational, financial, regulatory and supportive interventions that may
      influence health care professionals' choice to practice in underserved areas.
      Governments and educators should ensure that where interventions are implemented
      this is done within the context of a well-planned study so that the true effects
      of these measures on recruitment and long term retention can be determined in
      various settings.

PMID- 19160252
TI  - Pharmacotherapy and psychotherapy for body dysmorphic disorder.
AB  - BACKGROUND: Body dysmorphic disorder (BDD) is a prevalent and disabling
      preoccupation with a slight or imagined defect in appearance. Trials have
      investigated the use of serotonin reuptake inhibitors (SRIs) and cognitive
      behaviour therapy (CBT) for BDD. OBJECTIVES: To assess the efficacy of
      pharmacotherapy, psychotherapy or a combination of both treatment modalities for
      body dysmorphic disorder. SEARCH STRATEGY: We searched the Cochrane Depression,
      Anxiety and Neurosis Trial Register (December 2007), the Cochrane Central
      Register of Controlled Trials (The Cochrane Library Issue 4, 2007), MEDLINE
      (January 1966 to December 2007), and PsycINFO (1967 to December 2007). Ongoing
      and unpublished trials were located through searching the metaRegister of
      Controlled Trials, the CRISP and WHO ICTRP search portals (databases searched in
      December 2007), and through contacting key researchers and pharmaceutical
      companies. Additional studies were located through study reference lists.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) of patients meeting DSM
      or ICD diagnostic criteria for BDD, in which the trials compare pharmacotherapy,
      psychotherapy or multi-modal treatment groups with active or non-active control
      groups. Short or long-term trials were eligible. DATA COLLECTION AND ANALYSIS:
      Two review authors independently assessed RCTs for inclusion in the review,
      collated trial data, and assessed trial quality. Investigators were contacted to
      obtain missing data. Summary effect sizes for dichotomous and continuous outcomes
      were calculated using a random effects model and heterogeneity was assessed. MAIN
      RESULTS: Two pharmacotherapy and three psychotherapy trials were eligible for
      inclusion in the review, with data from four short-term RCTs (169 participants)
      available for analysis. Response data from a single placebo-controlled trial of
      fluoxetine suggested overall superiority of medication relative to placebo
      (relative risk (RR) 3.07, 95% CI 1.4 to 6.72, n = 67). Symptom severity was also
      significantly reduced in the RCTs of fluoxetine and clomipramine (relative to
      desipramine), as well as in the two CBT trials (WMD -44.96, 95% CI -54.43 to 
      35.49, n = 73). A low relapse rate (4/22) was demonstrated in one trial of CBT.
      AUTHORS' CONCLUSIONS: Results from the small number of available RCTs suggest
      that SRIs and CBT may be useful in treating patients with BDD. The findings of
      these studies need to be replicated. In addition, future controlled studies in
      other samples, such as adolescents, and using other selective SRIs, as well as a
      range of psychological therapy approaches and modalities (alone and in
      combination), are essential in supplementing the sparse data currently available.

PMID- 19160253
TI  - Combined psychotherapy plus benzodiazepines for panic disorder.
AB  - BACKGROUND: The efficacy of combining psychotherapy and benzodiazepines for panic
      disorder is unclear, despite widespread use. OBJECTIVES: To examine the efficacy
      of the combination compared with either treatment alone. SEARCH STRATEGY:
      Randomised trials comparing the combination of psychotherapy and benzodiazepine
      with either therapy alone for panic disorder were identified. The Cochrane
      Depression, Anxiety and Neurosis Group Studies and References Registers were
      searched. References of relevant trials and other reviews were checked. Experts
      in the field were contacted. Additional unpublished data were sought from authors
      of the original trials. SELECTION CRITERIA: Two authors independently checked the
      records retrieved by the searches to identify randomised trials comparing the
      combined therapy versus either of the monotherapies, among adults with panic
      disorder. DATA COLLECTION AND ANALYSIS: Two authors independently checked
      eligibility, assessed quality and extracted data from the eligible trials using a
      standardised data extraction form. The primary outcome was "response" based on
      global judgement. Random-effects meta-analyses were conducted, combining data
      from included trials. MAIN RESULTS: Three trials met eligibility criteria. A 16
      week behaviour therapy intervention was used in two trials, and a 12-week
      cognitive-behaviour therapy intervention in the third. Duration of follow-up
      varied, ranging from 0 to 12 months. Two trials (total 166 participants) provided
      data comparing combination with psychotherapy alone (both using behaviour
      therapy). No statistically significant differences were observed in response
      during the intervention (relative risk (RR) for combination 1.25, 95% CI 0.78 to
      2.03, P = 0.35), at the end of the intervention (RR 0.78, 0.45 to 1.35, P =
      0.37), or at the last follow-up time point, although the follow-up data suggested
      that the combination might be inferior to behaviour therapy alone (RR 0.62, 0.36
      to 1.07, P = 0.08). One trial (77 participants) compared combination with a
      benzodiazepine alone. No differences were found in response during the
      intervention (RR 1.57, 0.83 to 2.98, P = 0.17). Although the combination appeared
      to be superior to the benzodiazepine alone at the end of treatment (RR 3.39, 1.03
      to 11.21, P = 0.05) the finding was only borderline statistically significant,
      and no significant differences were observed at the 7-month follow-up (RR 2.31,
      0.79 to 6.74, P = 0.12). AUTHORS' CONCLUSIONS: The review established the paucity
      of high quality evidence investigating the efficacy of psychotherapy combined
      with benzodiazepines for panic disorder. Currently, there is inadequate evidence
      to assess the clinical effects of psychotherapy combined with benzodiazepines for
      patients who are diagnosed with panic disorder.

PMID- 19160254
TI  - Granulocyte transfusions for preventing infections in patients with neutropenia
      or neutrophil dysfunction.
AB  - BACKGROUND: Since the late 1990s there has been increasing demand for donated
      granulocyte transfusions to treat or prevent severe infections in patients who
      lack their own functional granulocytes. Other than in neonates, no systematic
      reviews have been performed for over 10 years relating to the efficacy of
      prophylactic granulocyte transfusions. OBJECTIVES: To determine the effectiveness
      and safety of granulocyte transfusions compared with a control population not
      receiving this intervention for preventing mortality due to infection or due to
      any other cause in patients with neutropenia or disorders of neutrophil function.
      SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) Issue 3, 2008, MEDLINE, EMBASE and other specialised databases up to
      October 2008. We also searched reference lists of articles and contacted experts
      in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing
      patients receiving granulocyte transfusions to prevent the development of
      infection with a control group receiving no granulocyte transfusions. Neonates
      have been the subject of a recent review and were excluded. There was no
      restriction by outcomes examined, but this review focuses on mortality, mortality
      due to infection and adverse events. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed potentially relevant studies for inclusion. Data
      were extracted by two review authors and the methodological quality was examined.
      Data were analysed using random and fixed effects models. MAIN RESULTS: Ten
      trials met the inclusion criteria. Allocation in all trials was random, with the
      control arm receiving no prophylactic therapy, except one trial in which the
      control group received specific prophylactic antibiotics. One study reported
      biological randomisation based upon the availability of suitably matched, related
      donors rather than strict randomisation. All trials were conducted over twenty
      years ago with one exception, a study from 2006 in which donors were pre
      medicated with granulocyte colony stimulating factor (G-CSF) resulting in
      significantly higher mean doses of granulocytes collected for transfusion.
      Different policies otherwise applied for the schedule for transfusion, method of
      granulocyte procurement and criteria for defining infection. Combining the
      results showed a relative risk (RR) for mortality of 0.94 (95% confidence
      intervals (CI) 0.71 to 1.25). Exclusion of the two trials which reported
      transfusion of an average number of granulocytes below 1 x 10(10) indicated a
      summary RR for mortality and mortality due to infection of 0.89 (CI 0.64 to 1.24)
      and 0.36 (0.14 to 0.96) respectively. AUTHORS' CONCLUSIONS:  IMPLICATIONS FOR
      CLINICAL PRACTICE: The controlled trials that have been identified raise the
      possibility that prophylactic granulocyte transfusions at a dose of at least 1 x
      10(10) may reduce the risk of mortality from infection. Overall mortality was not
      affected. However, the majority of studies were performed decades ago, and
      standards of supportive care have advanced considerably. These earlier trials
      were also based on transfusing lower yields of collected granulocytes than
      currently recommended. It is difficult to recommend prophylactic granulocyte
      transfusions outside the setting of ongoing controlled trials, given the resource
      and cost implications. IMPLICATIONS FOR RESEARCH: Larger trials are needed to
      establish the validity of the potential benefits raised by this review, in view
      of the methodological limitations, the small sample sizes and the heterogeneous
      definitions of infection that were encountered in the included studies.

PMID- 19160255
TI  - Antibiotics for mastitis in breastfeeding women.
AB  - BACKGROUND: Mastitis can be caused by ineffective positioning of the baby at the
      breast or restricted feeding. Infective mastitis is commonly caused by
      Staphylococcus Aureus. Incidence of mastitis in breastfeeding women may reach
      33%. Effective milk removal, pain medication and antibiotic therapy have been the
      mainstays of treatment. OBJECTIVES: This review aims to examine the effectiveness
      of antibiotic therapies in relieving symptoms for breastfeeding women with
      mastitis with or without laboratory investigation. SEARCH STRATEGY: We searched
      the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2007),
      the Cochrane Central Register of Clinical Trials (The Cochrane Library 2007,
      Issue 4), MEDLINE (1996 to 2007) and EMBASE (January 1985 to 2007). We contacted
      investigators and other content experts known to us for unpublished trials and
      scanned the reference lists of retrieved articles SELECTION CRITERIA: Randomized
      and quasi-randomized clinical trials comparing the effectiveness of various types
      of antibiotic therapies or antibiotic therapy versus alternative therapies for
      the treatment of mastitis were selected. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed trial quality and extracted data. When in dispute,
      we consulted a third author. MAIN RESULTS: Two trials met the inclusion criteria.
      One small trial (n = 25) compared amoxicillin with cephradine and found no
      significant difference between the two antibiotics in terms of symptom relief and
      abscess formation. Another, older study compared breast emptying alone as
      "supportive therapy" versus antibiotic therapy plus supportive therapy, and no
      therapy. The findings of the latter study suggested faster clearance of symptoms
      for women using antibiotics, although the study design was problematic. AUTHORS'
      CONCLUSIONS: There is insufficient evidence to confirm or refute the
      effectiveness of antibiotic therapy for the treatment of lactational mastitis.
      There is an urgent need to conduct high-quality, double-blinded randomized
      clinical trials to determine whether antibiotics should be used in this common
      postpartum condition.

PMID- 19160256
TI  - Corticosteroid injection for trigger finger in adults.
AB  - BACKGROUND: Trigger finger is a disease of the tendons of the hand leading to
      triggering (locking) of affected fingers, dysfunction and pain. Available
      treatments include local injection with corticosteroids, surgery, or splinting.
      OBJECTIVES: To summarize the evidence on the efficacy and safety of
      corticosteroid injections for trigger finger in adults using the following
      endpoints: treatment success, frequency of triggering or locking, functional
      status of the affected fingers, and severity of pain of the fingers. SEARCH
      STRATEGY: The databases CENTRAL, DARE, MEDLINE (1966 to November 2007), EMBASE
      (1956 to November 2007), CINAHL (1982 to November 2007), AMED (1985 to November
      2007) and PEDro (a physiotherapy evidence database) were searched. SELECTION
      CRITERIA: We selected randomized and controlled clinical trials evaluating
      efficacy and safety of corticosteroid injections for trigger finger in adults.
      DATA COLLECTION AND ANALYSIS: The databases were searched for titles of eligible
      studies. After screening abstracts of these studies, full text articles of
      studies which fulfilled the selection criteria were obtained. Data were extracted
      using a predefined electronic form. The methodological quality of included trials
      was assessed by using items from the checklist developed by Jadad and the Delphi
      list. We planned to extract data regarding information on the primary outcome
      measures: treatment success, frequency of triggering or locking, and functional
      impairment of fingers, severity of the trigger finger; and the secondary outcome
      measures: proportion of patients with side effects, types of side effects, and
      patient satisfaction with injection. MAIN RESULTS: Two randomized controlled
      studies were found that involved 63 participants: 34 were allocated to
      corticosteroids and lidocaine, and 29 were allocated to lidocaine alone.
      Corticosteroid injection with lidocaine was more effective than lidocaine alone
      on treatment success at four weeks (relative risk 3.15, 95% CI 1.34 to 7.40). The
      number needed to treat to benefit was 3. No adverse events or side effects were
      reported. AUTHORS' CONCLUSIONS: The effectiveness of local corticosteroid
      injections was studied in only two small randomized controlled trials of poor
      methodological quality. Both studies showed better short-term effects of
      corticosteroid injection combined with lidocaine compared to lidocaine alone on
      the treatment success outcome. In one study the effects of corticosteroid
      injections lasted up to four months. No adverse effects were observed. The
      available evidence for the effectiveness of intra-tendon sheath corticosteroid
      injection for trigger finger can be graded as a silver level evidence for
      superiority of corticosteroid injections combined with lidocaine over injections
      with lidocaine alone.

PMID- 19160257
TI  - Steroid avoidance or withdrawal for kidney transplant recipients.
AB  - BACKGROUND: Steroid-sparing strategies have been attempted during the last two
      decades in order to avoid morbidity in kidney transplant recipients. Previous
      systematic reviews of steroid withdrawal after kidney transplantation have shown
      significant increases in acute rejection and an increase in graft failure rates.
      Steroid avoidance in kidney transplantation is increasingly attempted and the
      possible benefits or harms have never been a subject of a systematic review.
      OBJECTIVES: To assess the safety and efficacy of steroid withdrawal or avoidance
      in patients receiving a kidney transplant. SEARCH STRATEGY: We searched CENTRAL,
      MEDLINE and EMBASE, references lists and abstracts from international
      transplantation society scientific meetings. SELECTION CRITERIA: Randomised
      controlled studies (RCTs) of steroid avoidance or withdrawal were included
      providing that one treatment arm consisted in steroid avoidance or withdrawal and
      intention-to-treat rates of acute rejection and graft failure were clearly
      established after steroid avoidance or use or withdrawal or continuation.
      Observational studies were tabulated. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trial quality and extracted data. Statistical analyses
      were performed using the random effects model and results expressed as risk ratio
      (RR) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: We
      included 30 RCTs (5949 participants). Steroid-sparing strategies showed no effect
      on mortality or graft loss including death. Patients on any steroid-sparing
      strategy showed a higher risk of graft loss excluding death than those with
      conventional steroid use (RR 1.23, 95% CI 1.00 to 1.52), especially in those not
      receiving MMF/Myf or everolimus (RR 1.70, 95% CI 1.00 to 2.90). Acute rejection
      was more frequent with a steroid-sparing strategy (RR 1.27, 95% CI 1.14 to 1.40)
      and more frequent after steroid withdrawal or avoidance when compared with
      standard steroid treatment when cyclosporin (CsA) was used. Steroid-sparing and
      withdrawal strategies showed benefits in reducing antihypertensive drug need,
      serum cholesterol, antihyperlipidaemic drug need, new-onset diabetes after
      transplantation (NODAT) requiring any treatment and cataracts. Steroid avoidance
      did not alter serum cholesterol, but was associated with less frequent NODAT
      requiring any treatment. Cardiovascular events were reduced with steroid
      avoidance. Reduced antihypertensive drug need and serum cholesterol were similar
      with CsA or tacrolimus (TAC). Reduced antihyperlipidaemic drug need was only
      evident with TAC, whereas the reduction in NODAT requiring any treatment was only
      evident with CsA. Infection was lower in steroid-sparing patients using CsA (RR
      0.88, 95% CI 0.78 to 1.00). NODAT requiring any treatment was less frequent with
      steroid avoidance than with steroid withdrawal. AUTHORS' CONCLUSIONS: This review
      confirms that steroid avoidance and steroid withdrawal strategies in kidney
      transplantation are not associated with increased mortality or graft loss despite
      an increase in acute rejection. These immunosuppression strategies may allow safe
      steroid avoidance or elimination a few days after kidney transplantation if
      antibody induction treatment is prescribed or after three to six months if such
      induction is not used.

PMID- 19160258
TI  - Treatments for suppression of lactation.
AB  - BACKGROUND: Various pharmacologic and nonpharmacologic interventions have been
      used to suppress lactation after childbirth and relieve associated symptoms.
      Despite the large volume of literature on the subject, there is currently no
      universal guideline on the most appropriate approach for suppressing lactation in
      postpartum women. OBJECTIVES: To evaluate the effectiveness and safety of
      interventions used for suppression of lactation in postpartum women (who have not
      breastfed or expressed breastmilk) to determine which approach has the greatest
      comparative benefits with least risk. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (October 2007). SELECTION
      CRITERIA: Randomised trials evaluating the effectiveness of treatments used for
      suppression of postpartum lactation. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trial quality and extracted data. MAIN RESULTS: We
      included 46 trials (5164 women). The trials were generally small and of limited
      quality. Five trials (206 women) indicated that bromocriptine significantly
      reduced the proportion of women lactating compared to no treatment at or within
      seven days postpartum (three trials, 107 women; relative risk (RR) 0.36, 95%
      confidence interval (CI) 0.24 to 0.54). Six trials involving oestrogen
      preparations (diethylstilbestrol, quinestrol, chlorotrianisene, hexestrol)
      suggested that they significantly reduced the proportion of lactating women
      compared to no treatment at or within seven days postpartum (RR 0.41, 95% CI 0.29
      to 0.59). We found no trials comparing nonpharmacologic methods with no
      treatment. Trials comparing bromocriptine with other pharmacologic agents
      suggested similarity in their effectiveness (RR 0.79, 95% CI 0.54 to 1.17). Side
      effects were poorly reported in the trials and no case of thromboembolism was
      recorded in the four trials that reported it as an outcome. AUTHORS' CONCLUSIONS:
      There is weak evidence that some pharmacologic treatments (most of which are
      currently unavailable to the public) are better than no treatment for suppressing
      lactation symptoms in the first postpartum week. No evidence currently exists to
      indicate whether nonpharmacologic approaches are more effective than no
      treatment. Presently, there is insufficient evidence to address the side effects
      of methods employed for suppressing lactation. When women desire treatment,
      bromocriptine may be considered where it is registered for lactation suppression
      in those without predisposition to its major side effects of public concerns.
      Large randomised trials are needed to compare the effectiveness of pharmacologic
      (especially bromocriptine) and nonpharmacologic methods to no treatment. Such
      trials should consider acceptability of the intervention and lactation symptoms
      of concern to women and be large enough to detect clinically important
      differences in major side effects between comparison groups.

PMID- 19160259
TI  - Maintenance therapy with oxytocin antagonists for inhibiting preterm birth after
      threatened preterm labour.
AB  - BACKGROUND: In some women, an episode of preterm labour settles and does not
      result in immediate preterm birth. Subsequent treatment with tocolytic agents
      such as oxytocin receptor antagonists may then have the potential to prevent the
      recurrence of preterm labour, prolonging gestation, and preventing the adverse
      consequences of prematurity for the infant. OBJECTIVES: To assess the effects of
      maintenance therapy with oxytocin antagonists administered by any route after an
      episode of preterm labour in order to delay or prevent preterm birth. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (June 2008), sought ongoing and unpublished trials by contacting experts
      in the field and searched the reference lists of relevant articles. SELECTION
      CRITERIA: Randomised controlled trials comparing oxytocin antagonists with any
      alternative tocolytic agent, placebo or no treatment, used for maintenance
      therapy after an episode of preterm labour. DATA COLLECTION AND ANALYSIS:
      Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and
      Childbirth Group were used. Two review authors independently undertook evaluation
      of methodological quality and extracted trial data. MAIN RESULTS: This review
      includes one trial of 513 women. When compared with placebo, atosiban did not
      reduce preterm birth before 37 weeks (risk risk (RR) 0.89; 95% confidence
      intervals (CI) 0.71 to 1.12), 32 weeks (RR 0.85; 95% CI 0.47 to 1.55), or 28
      weeks (RR 0.75; 95% CI 0.28 to 2.01). No difference was shown in neonatal
      morbidity, or perinatal mortality. AUTHORS' CONCLUSIONS: There is insufficient
      evidence to support the use of oxytocin receptor antagonists to inhibit preterm
      birth after a period of threatened or actual preterm labour. Any future trials
      using oxytocin antagonists or other drugs as maintenance therapy for preventing
      preterm birth should examine a variety of important infant outcome measures,
      including reduction of neonatal morbidity and mortality, and long-term infant
      follow up. Future research should also focus on the pathophysiological pathways
      that precede preterm labour.

PMID- 19160261
TI  - Oxygen therapy for lower respiratory tract infections in children between 3
      months and 15 years of age.
AB  - BACKGROUND: Usual practice in lower respiratory tract infections (LRTIs) includes
      administering complementary oxygen. The effectiveness of oxygen therapy and
      different methods of delivery is unknown. This review contributes to the rational
      use of oxygen in the treatment of LRTIs. OBJECTIVES: To determine in the
      treatment of LRTIs: the effectiveness of oxygen therapy and oxygen delivery
      methods; the safety of these methods; and indications for oxygen therapy. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library, 2008, issue 2); MEDLINE (January 1966 to March
      2008); EMBASE (1990 to December 2007); and LILACS (January 1982 to March 2008).
      SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oxygen versus
      no oxygen therapy or methods of oxygen delivery for hypoxaemic LRTIs in children
      (3 months to 15 years of age). To determine indications for oxygen therapy,
      observational studies were included. DATA COLLECTION AND ANALYSIS: We assessed
      551 titles. No studies comparing oxygen versus no oxygen were found. Four RCTs
      comparing delivery methods and 12 observational studies assessing the accuracy of
      clinical signs indicating hypoxaemia were eligible. A meta-analysis of the RCTs
      comparing oxygen delivery methods was performed. MAIN RESULTS: Three studies
      assessed the effectiveness of nasal prongs (NP) versus nasopharyngeal catheters
      (NPC). The pooled estimate effect showed no differences (OR 0.96; 95% CI 0.48 to
      1.93) in treatment failure (number of children failing to achieve adequate SaO2).
      One study compared the effectiveness of NP versus nasal catheter (NC). No
      differences were found in treatment failure (the mean number of episodes of
      desaturation/child: NC group 2.75, SD +/- 2.18 episodes/child; NP group 3, SD +/-
      2.5 episodes/child, p = 0.64). Another study compared face mask (FM) and head box
      (HB) versus NPC. Use of FM showed lower risk of treatment failure (failure to
      achieve PaO2 > 60 mmHg) than the NPC (OR 0.20; 95% CI 0.55 to 0.88). As did the
      use of HB compared with NPC (OR 0.40; 95% CI 0.13 to 1.12).Studies assessing the
      accuracy of signs and/or symptoms indicating hypoxaemia showed that cyanosis,
      grunting, difficulty in feeding and mental alertness have better specificity in
      predicting hypoxaemia and its results were consistent among studies. AUTHORS'
      CONCLUSIONS: NP and NPC seem to be similar in effectiveness and safety when used
      in patients with LRTI. There is no single clinical sign or symptom that
      accurately identifies hypoxaemia. Studies identifying the most effective and safe
      oxygen delivery method are needed.

PMID- 19160262
TI  - Hormone therapy for endometriosis and surgical menopause.
AB  - BACKGROUND: Endometriosis is characterized by the presence of ectopic endometrial
      tissue that might lead to many distressing and debilitating symptoms. Despite
      available studies supporting standard hormone therapy for women with
      endometriosis and post-surgical menopause, there is still a concern that
      estrogens may induce a recurrence of the disease and its symptoms. OBJECTIVES:
      This review aimed to look at pain and disease recurrence in women with
      endometriosis who used hormone therapy for post-surgical menopause. SEARCH
      STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group
      Specialized Register (March 2008), Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1966 to March 2008),
      EMBASE (1980 to March 2008), and references lists of articles. Relevant journals
      and conference proceedings were handsearched. SELECTION CRITERIA: Randomized
      controlled trials studying hormone therapy for women with endometriosis in post
      surgical menopause. DATA COLLECTION AND ANALYSIS: Review authors assessed the
      eligibility of trials and their quality. MAIN RESULTS: Two studies fulfilled our
      inclusion criteria. One trial compared the nonstop transdermal application of
      17beta-estradiol (0.05 mg/day) combined with cyclic medroxy progesterone acetate
      (10 mg per day) for 12 days per month in women with a conserved uterus with
      nonstop tibolone (2.5 mg/day). The second trial used sequential administration of
      estrogens and progesterone with two 22 cm(2) patches applied weekly to produce a
      controlled release of 0.05 mg/day. Micronized progesterone was administered
      orally (200 mg/day) for 14 days with a 16-day interval free of treatment. Pain
      and dyspareunia The first trial reported recurrence of pain in the estrogen and
      progesterone arm in 4/10 of women compared with 1/11 in the tibilone arm. In the
      latter, 4/115 women reported recurrence of pain in the treatment group compared
      with 0/57 patients in the no-treatment arm. Neither finding was statistically
      different.Confirmed recurrence or exacerbation of endometriosis This outcome was
      not reported in the first trial. The second found that 2/115 of the treatment
      group developed recurrence of endometriosis with no recurrence reported in the no
      treatment group. This was not statistically significant. No woman was re-operated
      on in the no-treatment group compared with 2/115 in the treatment group. AUTHORS'
      CONCLUSIONS: Hormone replacement therapy for women with endometriosis in post
      surgical menopause could result in pain and disease recurrence. However, the
      evidence in the literature is not strong enough to suggest depriving severely
      symptomatic patients from this treatment. There is a need for more randomised
      controlled studies.

PMID- 19160260
TI  - Advance treatment directives for people with severe mental illness.
AB  - BACKGROUND: An advance directive is a document specifying a person's preferences
      for treatment, should he or she lose capacity to make such decisions in the
      future. They have been used in end-of-life settings to direct care but should be
      well suited to the mental health setting. OBJECTIVES: To examine the effects of
      advance treatment directives for people with severe mental illness. SEARCH
      STRATEGY: We searched the Cochrane Schizophrenia Group's Register (February
      2008), the Cochrane Library (Issue 1 2008), BIOSIS (1985 to February 2008),
      CINAHL (1982 to February 2008), EMBASE (1980 to February 2008), MEDLINE (1966 to
      February 2008), PsycINFO (1872 to February 2008), as well as SCISEARCH and Google
      - Internet search engine (February 2008). We inspected relevant references and
      contacted first authors of included studies. SELECTION CRITERIA: We included all
      randomised controlled trials (RCTs), involving adults with severe mental illness,
      comparing any form of advance directive with standard care for health service and
      clinical outcomes. DATA COLLECTION AND ANALYSIS: We extracted data independently.
      For homogenous dichotomous data we calculated fixed-effect relative risk (RR) and
      95% confidence intervals (CI) on an intention-to-treat basis. For continuous
      data, we calculated weighted mean differences (WMD) and their 95% confidence
      interval again using a fixed-effect model. MAIN RESULTS: We were able to include
      two trials involving 321 people with severe mental illnesses. There was no
      significant difference in hospital admission (n=160, 1 RCT, RR 0.69 0.5 to 1.0),
      or number of psychiatric outpatient attendances between participants given
      advanced treatment directives or usual care. Similarly, no significant
      differences were found for compliance with treatment, self harm or number of
      arrests. Participants given advanced treatment directives needed less use of
      social workers time (n=160, 1 RCT, WMD -106.00 CI -156.2 to -55.8) than the usual
      care group, and violent acts were also lower in the advanced directives group
      (n=160, 1 RCT, RR 0.27 CI 0.1 to 0.9, NNT 8 CI 6 to 92). The number of people
      leaving the study early were not different between groups (n=321, 2 RCTs, RR 0.92
      CI 0.6 to 1.6). AUTHORS' CONCLUSIONS: There are too few data available to make
      definitive recommendations. More intensive forms of advance directive appear to
      show promise, but currently practice must be guided by evidence other than that
      derived from randomised trials. More trials are indicated to determine whether
      higher intensity interventions, such as joint crisis planning, have an effect on
      outcomes of clinical relevance.

PMID- 19160263
TI  - Interval debulking surgery for advanced epithelial ovarian cancer.
AB  - BACKGROUND: Primary debulking surgery, a crucial step in the management of
      epithelial ovarian cancer, is not always an option in patients with advanced
      stage disease (stage III to IV). In some circumstances, surgery may not yield
      satisfactory results with residual tumour masses > 1 to 2 cm (so called
      suboptimal surgery). Induction or neoadjuvant chemotherapy followed by interval
      debulking surgery (IDS) may have an alternative role in this setting. However,
      the advantage of IDS compared to conventional methods is still a controversial
      issue. OBJECTIVES: To assess the effectiveness and complications of IDS for
      patients with advanced stage epithelial ovarian cancer. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL), (The
      Cochrane Library, Issue 2, 2008), MEDLINE (January 1966 to June 2008), EMBASE
      (January 1966 to June 2008), and reference lists of included studies. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing survival of women with
      advanced epithelial ovarian cancer, who had IDS performed between cycles of
      chemotherapy after primary surgery with survival of women who had conventional
      treatment (primary debulking surgery and adjuvant chemotherapy). DATA COLLECTION
      AND ANALYSIS: Two review authors independently assessed trial quality and
      extracted data. Searches for additional information from study authors were
      attempted. Meta-analysis of overall and progression free survival (PFS) was
      performed using fixed effects models. MAIN RESULTS: Three RCTs, randomising 853
      women of whom 781 were evaluated, met the inclusion criteria. Overall survival
      (OS) showed substantial heterogeneity between trials (I2 = 58%). Subgroup
      analysis for overall survival in two trials, wherein the primary surgery was not
      performed by gynecologic oncologists or was less extensive, showed a benefit of
      IDS: (relative risk) RR = 0.7 (95% confidence interval (CI): 0.5 to 0.9, I2 =
      0%). Likewise, substantial heterogeneity between two trials for PFS evaluating
      702 women was also shown (I(2) =75%). Rates of toxic reactions to chemotherapy
      were similar in both arms (RR = 1.3, 95%CI: 0.4 to 3.6), but little information
      is available for other adverse events. Only one trial reported quality of life
      (QOL), which was generally similar in both treatment arms. AUTHORS' CONCLUSIONS:
      No conclusive evidence was found to determine whether IDS between cycles of
      chemotherapy would improve or decrease the survival rates of women with advanced
      ovarian cancer, compared with conventional treatment of primary surgery followed
      by adjuvant chemotherapy. IDS appeared to yield benefit only in the patients
      whose primary surgery was not performed by gynecologic oncologists or was less
      extensive. Data on QOL and adverse events were inconclusive.

PMID- 19160264
TI  - Preoperative chemoradiation versus radiation alone for stage II and III
      resectable rectal cancer.
AB  - BACKGROUND: Preoperative radiotherapy (RT) decreases local recurrence rate and
      improves survival in stage II and III rectal cancer patients. The combination of
      chemotherapy with RT has a sound radiobiological rationale, and phase II trials
      of combined chemoradiation (CRT) have shown promising activity in rectal cancer.
      OBJECTIVES: To compare preoperative RT with preoperative CRT in patients with
      resectable stage II and III rectal cancer. SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials, Web of Science, Embase.com, and
      Pubmed from 1975 until june 2007. A manual search was performed of Ann Surg, Arch
      Surg, Cancer, J Clin Oncol, Int J Radiat Oncol Biol Phys and the proceedings of
      ASTRO, ECCO and ASCO from 1990 until june 2007. SELECTION CRITERIA: Relevant
      studies randomized resectable stage II or III rectal cancer patients to at least
      one arm of preoperative RT alone or at least one arm of preoperative CRT. DATA
      COLLECTION AND ANALYSIS: Primary outcome parameters included overall survival
      (OS) at 5 years and local recurrence (LR) rate at 5 years. Secondary outcome
      parameters included disease free survival (DFS) at 5 years, metastasis rate,
      pathological complete response rate, clinical response rate, sphincter
      preservation rate, acute toxicity, postoperative mortality and morbidity, and
      anastomotic leak rate. Outcome parameters were summarized using the Odds Ratio
      (OR) and associated 95% confidence interval (CI) using the fixed effects model.
      MAIN RESULTS: Four trials were identified and included in the meta-analysis. The
      addition of chemotherapy to preoperative RT significantly increased grade III and
      IV acute toxicity (OR 1.68-10, P = 0.002) while no differences were observed in
      postoperative morbidity or mortality. Compared to preoperative RT alone,
      preoperative CRT significantly increased the rate of complete pathological
      response (OR 2.52-5.27, P < 0.001) although this did not translate into a higher
      sphincter preservation rate (OR 0.92-1.31, P = 0.29). The incidence of local
      recurrence at five years was significantly lower in the CRT group compared to RT
      alone (OR 0.39-0.72, P < 0.001). No statistically significant differences were
      observed in DFS (OR 0.92-1.34, P = 0.27) or OS (OR 0.79-1.14, P = 0.58) at five
      years. AUTHORS' CONCLUSIONS: Compared to preoperative RT alone, preoperative CRT
      enhances pathological response and improves local control in resectable stage II
      and III rectal cancer, but does not benefit disease free or overall survival. The
      effects of preoperative CRT on functional outcome and quality of life are
      incompletely understood and should be addressed in future trials.

PMID- 19160265
TI  - Interventions for promoting information and communication technologies adoption
      in healthcare professionals.
AB  - BACKGROUND: Information and communication technologies (ICT) are defined as
      digital and analogue technologies that facilitate the capturing, processing,
      storage and exchange of information via electronic communication. ICTs have the
      potential to improve information management, access to health services, quality
      of care, continuity of services, and cost containment. Knowledge is lacking on
      conditions for successful ICT integration into practice. OBJECTIVES: To carry out
      a systematic review of the effectiveness of interventions to promote the adoption
      of ICT by healthcare professionals. SEARCH STRATEGY: Specific strategies, defined
      with the help of an information specialist, were used to search the Cochrane
      Effective Practice and Organisation of Care Group (EPOC) register and additional
      relevant databases. We considered studies published from January 1990 until
      October 2007. SELECTION CRITERIA: Randomised controlled trials (RCTs), controlled
      clinical trials (CCTs), controlled before/after studies (CBAs), and interrupted
      time series (ITS) that reported objectively measured outcomes concerning the
      effect of interventions to promote adoption of ICT in healthcare professionals'
      practices. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      each potentially relevant study for inclusion. We resolved discrepancies by
      discussion or a third reviewer. Two teams of two reviewers independently
      extracted data and assessed the quality of included studies. A meta-analysis of
      study outcomes was not possible, given the small number of included studies and
      the heterogeneity of intervention and outcomes measures. We conducted qualitative
      analyses, and have presented the results in a narrative format. MAIN RESULTS: Ten
      studies met the inclusion criteria. Nine of them were RCTs. All studies involved
      physicians as participants (including postgraduate trainees), and one study also
      included other participants. Only two studies measured patient outcomes.
      Searching skills and/or frequency of use of electronic databases, mainly MEDLINE,
      were targeted in eight studies. Use of Internet for audit and feedback, and email
      for provider-patient communication, were targeted in two studies. Four studies
      showed small to moderate positive effects of the intervention on ICT adoption.
      Four studies were unable to demonstrate significant positive effects, and the two
      others showed mixed effects. No studies looked at the long-term effect or
      sustainability of the intervention. AUTHORS' CONCLUSIONS: There is very limited
      evidence on effective interventions promoting the adoption of ICTs by healthcare
      professionals. Small effects have been reported for interventions targeting the
      use of electronic databases and digital libraries. The effectiveness of
      interventions to promote ICT adoption in healthcare settings remains uncertain,
      and more well designed trials are needed.

PMID- 19160266
TI  - Treatment for familial amyotrophic lateral sclerosis/motor neuron disease.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS), also known as motor neuron
      disease (MND), is a rare neurodegenerative disease. Approximately 5% to 7% of
      ALS/MND patients report a family history of a similarly affected relative.
      Superoxide dismutase-1 gene mutations are the cause in about 20% of familial
      cases. In those with non-familial (sporadic) ALS/MND the cause is unknown. Also
      unknown is whether patients with familial and sporadic ALS/MND respond
      differently to treatment. OBJECTIVES: To systematically review the literature and
      to answer the specific question: 'Is there a difference in the response to
      treatment between patients with sporadic and familial forms of ALS?' SEARCH
      STRATEGY: In May 2006 we searched the Cochrane Neuromuscular Disease Group Trials
      Register, MEDLINE (January 1966 to May 2006) and EMBASE (January 1980 to May
      2006) for randomized controlled trials (RCTs). Two review authors read the titles
      and abstracts of all articles and reviewed the full text of all possibly relevant
      articles. We scanned references of all included trials to identify additional
      relevant articles. For all trials eligible for inclusion we contacted the authors
      to request the necessary raw data. SELECTION CRITERIA: Studies had to meet two
      criteria: (a) randomized controlled study design, and (b) inclusion of patients
      with both familial and sporadic ALS/MND. DATA COLLECTION AND ANALYSIS: We
      attempted to contact authors of all trials that met inclusion criteria. We
      obtained data regarding ALS/MND type (sporadic versus familial), treatment
      assignment (active versus placebo), survival and ALS Functional Rating Scale
      scores for four large RCTs that included 822 sporadic and 41 familial ALS
      patients. We could not obtain data from 25 potentially eligible studies (17 trial
      authors could not be contacted and eight were unwilling to provide data). MAIN
      RESULTS: There was no statistical evidence for a different response to treatment
      in patients with familial ALS/MND compared to those with sporadic ALS/MND. The
      pooled estimate of the hazard ratio for the interaction term (treatment x
      familial ALS) suggested a more beneficial response with respect to survival among
      patients with familial ALS/MND, but the result was not statistically significant.
      Estimates of the rate of decline on the ALS Functional Rating Scale also
      suggested a slightly better response to treatment among those with familial
      ALS/MND, but the result was not statistically significant. AUTHORS' CONCLUSIONS:
      Future RCTs should document whether patients with familial ALS/MND are included
      and the presence or absence of a mutation in the superoxide dismutase-1 gene
      amongst those with familial ALS/MND.

PMID- 19160267
TI  - Prenatal education for congenital toxoplasmosis.
AB  - BACKGROUND: Congenital toxoplasmosis is considered a rare but potentially severe
      infection. Prenatal education about congenital toxoplasmosis could be the most
      efficient and least harmful intervention, yet its effectiveness is uncertain.
      OBJECTIVES: To assess the effects of prenatal education for preventing congenital
      toxoplasmosis. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (November 2007), CENTRAL (The Cochrane Library 2007,
      Issue 3), MEDLINE (1966 to November 2007), EMBASE (1980 to November 2007), CINAHL
      (1982 to November 2007), LILACS (1982 to November 2007) IMEMR (1984 to November
      2007), and reference lists of relevant papers, reviews and websites. SELECTION
      CRITERIA: Randomized and quasi-randomized controlled trials (RCT) of all types of
      prenatal education on toxoplasmosis infection during pregnancy. DATA COLLECTION
      AND ANALYSIS: Three authors independently assessed study quality and extracted
      data. MAIN RESULTS: One cluster-randomized controlled trial (432 women) met the
      inclusion criteria. However, the overall methodological quality was poor. The
      authors did not report measure of association but only provided P values (P less
      than 0.05) for all outcomes. The authors concluded that prenatal education can
      effectively change pregnant women's behavior as it increased pet, personal and
      food hygiene. There are no randomized trials on the effect of prenatal education
      on congenital toxoplasmosis rate, or toxoplasmosis seroconversion rate during
      pregnancy, but three observational studies consistently suggest that prenatal
      education might have a positive impact on these outcomes. AUTHORS' CONCLUSIONS:
      Even though primary prevention of congenital toxoplasmosis is considered a
      desirable intervention, given the lack of related risks compared to secondary and
      tertiary prevention, its effectiveness has not been adequately evaluated. There
      is very little evidence from RCTs that prenatal education is effective in
      reducing congenital toxoplasmosis even though evidence from observational studies
      suggests it is. Given the lack of good evidence supporting prenatal education for
      congenital toxoplasmosis prevention, further RCTs are needed to confirm any
      potential benefits and to further quantify the impact of different sets of
      educational intervention.

PMID- 19160268
TI  - Very early versus delayed mobilisation after stroke.
AB  - BACKGROUND: Very early mobilisation is performed in some stroke units and
      recommended in acute stroke clinical guidelines. It is unclear whether very early
      mobilisation independently improves outcome after stroke. OBJECTIVES: To
      determine the benefits and harms of very early mobilisation (commenced within 48
      hours of stroke) compared with conventional care. SEARCH STRATEGY: We searched
      the Cochrane Stroke Group Trials Register (last searched April 2008). In
      addition, we searched 25 databases including the Cochrane Central Register of
      Controlled Trials (The Cochrane Library Issue 3, 2007), MEDLINE (1950 to August
      2007), EMBASE (1980 to September 2007), CINAHL (1982 to December 2006), and AMED
      (1985 to January 2007). We also searched relevant ongoing trials and research
      registers (searched January 2007) and the Chinese medical database Wanfangdata
      (searched March 2007), handsearched journals, searched reference lists and
      contacted researchers in the field. SELECTION CRITERIA: Unconfounded RCTs of
      acute stroke patients, comparing an intervention group that started out of bed
      mobilisation within 48 hours of stroke and aimed to reduce time to first
      mobilisation and/or increase the amount or frequency (or both) of mobilisation,
      with conventional care. DATA COLLECTION AND ANALYSIS: One review author
      eliminated obviously irrelevant records; two review authors independently applied
      selection criteria to remaining studies. The primary outcome was death or poor
      outcome (dependency or institutionalisation) at the end of scheduled follow up.
      Secondary outcomes included mortality, dependency, institutionalisation,
      activities of daily living (ADLs), quality of life, time to walking, adverse
      events (e.g. deep vein thrombosis) and patient mood. MAIN RESULTS: One study,
      involving 71 participants, was included. In this study the experimental group had
      earlier and more frequent mobilisation than the control group (median 18.1 hours
      post stroke for experimental group versus 30.8 hours control; 167 minutes of
      mobilisation (interquartile range (IQR) 62 to 305) during admission for
      experimental group versus 69 (IQR 31 to 115) minutes control). Fewer patients who
      received early and frequent mobilisation were dead or disabled at three months,
      but this was not statistically significant and the confidence intervals were wide
      (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.25 to 1.79, P = 0.42). No
      significant difference on any secondary outcomes of interest were found. AUTHORS'
      CONCLUSIONS: We found insufficient evidence to support or refute the efficacy of
      routine very early mobilisation after stroke, compared with conventional care.
      More research is required to determine the benefits and harms of very early
      mobilisation after stroke.

PMID- 19160269
TI  - Interventions for preventing weight gain after smoking cessation.
AB  - BACKGROUND: Most people who stop smoking gain weight, on average about 7 kg in
      the long term. There are some interventions that have been specifically designed
      to tackle smoking cessation whilst also limiting weight gain. Many smoking
      cessation pharmacotherapies and other interventions may also limit weight gain.
      OBJECTIVES: This review is divided into two parts. (1) Interventions designed
      specifically to aid smoking cessation and limit post-cessation weight gain (2)
      Interventions designed to aid smoking cessation that may also plausibly have an
      effect on weight SEARCH STRATEGY: Part 1: We searched the Cochrane Tobacco
      Addiction Group's Specialized Register which includes trials indexed in MEDLINE,
      EMBASE, SciSearch and PsycINFO, and other reviews and conference abstracts. Part
      2: We searched the included studies of Cochrane smoking cessation reviews of
      nicotine replacement therapy, antidepressants, nicotine receptor partial
      agonists, cannabinoid type 1 receptor antagonists (rimonabant), and exercise
      interventions, published in Issue 4, 2008 of The Cochrane Library. SELECTION
      CRITERIA: Part 1: We included trials of interventions designed specifically to
      address both smoking cessation and post-cessation weight gain that had measured
      weight at any follow-up point and/or smoking six months or more after
      quitting.Part 2: We included trials from the selected Cochrane reviews that could
      plausibly modify post-cessation weight gain if they had reported weight gain by
      trial arm at end of treatment or later. DATA COLLECTION AND ANALYSIS: We
      extracted data in duplicate on smoking and weight for part 1 trials, and on
      weight only for part 2. Abstinence from smoking is expressed as a risk ratio
      (RR), using the most rigorous definition of abstinence available in each trial,
      and biochemically validated rates if available. The outcome is expressed as the
      difference in weight change between trial arms from baseline. Where appropriate,
      we performed meta-analysis using the Mantel-Haenszel method for smoking and
      inverse variance for weight using a fixed-effect model. MAIN RESULTS: We found
      evidence that pharmacological interventions aimed at reducing post-cessation
      weight gain resulted in a significant reduction in weight gain at the end of
      treatment (dexfenfluramine (-2.50kg [-2.98kg to -2.02kg], fluoxetine (-0.80kg [
      1.27kg to -0.33kg], phenylpropanolamine (PPA) (-0.50kg [-0.80kg to -0.20kg],
      naltrexone (-0.76kg [-1.51kg to -0.01kg])). No evidence of maintenance of the
      treatment effect was found at six or 12 months.Among the behavioural
      interventions, only weight control advice was associated with no reduction in
      weight gain and with a possible reduction in abstinence. Individualized
      programmes were associated with reduced weight gain at end of treatment and at 12
      months (-2.58kg [-5.11kg to -0.05kg]), and with no effect on abstinence (RR 0.74
      [0.39 to 1.43]). Very low calorie diets (-1.30kg (-3.49kg to 0.89kg] at 12
      months) and cognitive behavioural therapy (CBT) (-5.20kg (-9.28kg to -1.12kg] at
      12 months) were both associated with improved abstinence and reduced weight gain
      at end of treatment and at long-term follow up.Both bupropion (300mg/day) and
      fluoxetine (30mg and 60mg/day combined) were found to limit post-cessation weight
      gain at the end of treatment (-0.76kg [-1.17kg to -0.35kg] I(2)=48%) and -1.30kg
      [-1.91kg to -0.69kg]) respectively. There was no evidence that the weight
      reducing effect of bupropion was dose-dependent. The effect of bupropion at one
      year was smaller and confidence intervals included no effect (-0.38kg [-2.001kg
      to 1.24kg]).We found no evidence that exercise interventions significantly
      reduced post-cessation weight gain at end of treatment but evidence for an effect
      at 12 months (-2.07kg [-3.78kg, -0.36kg]).Treatment with NRT resulted in
      attenuation of post-cessation weight gain (-0.45kg [-0.70kg, -0.20kg]) at the end
      of treatment, with no evidence that the effect differed for different forms of
      NRT. The estimated weight gain reduction was similar at 12 months (-0.42kg [
      0.92kg, 0.08kg]) but the confidence intervals included no effect.There were no
      relevant data on the effect of rimonabant on weight gain.We found no evidence
      that varenicline significantly reduced post-cessation weight gain at end of
      treatment and no follow-up data are currently available. One study randomizing
      successful quitters to 12 more weeks of active treatment showed weight to be
      reduced by 0.71kg (-1.04kg to -0.38kg). In three studies, participants taking
      bupropion gained significantly less weight at the end of treatment than those on
      varenicline (-0.51kg [-0.93kg to -0.09kg]). AUTHORS' CONCLUSIONS: Behavioural
      interventions of general advice only are not effective and may reduce abstinence.
      Individualized interventions, very low calorie diets, and CBT may be effective
      and not reduce abstinence. Exercise interventions are not associated with reduced
      weight gain at end of treatment, but may be associated with worthwhile reductions
      in weight gain in the long term, Bupropion, fluoxetine, nicotine replacement
      therapy, and probably varenicline all reduced weight gain while being used.
      Although this effect was not maintained one year after quitting for bupropion,
      fluoxetine, and nicotine replacement, the evidence is insufficient to exclude a
      modest long-term effect. The data are not sufficient to make strong clinical
      recommendations for effective programmes.

PMID- 19160270
TI  - Driving assessment for maintaining mobility and safety in drivers with dementia.
AB  - BACKGROUND: Demographic changes are leading to an increase in the number of older
      drivers: as dementia is an age-related disease, there is also an increase in the
      numbers of drivers with dementia. Dementia can impact on both the mobility and
      safety of drivers, and the impact of formal assessment of driving is unknown in
      terms of either mobility or safety. Those involved in assessment of older drivers
      need to be aware of the evidence of positive and negative effects of driving
      assessment. Although cognitive tests are felt by some authors to have poor face
      and construct validity for assessing driving performance, extrapolating from
      values in one large-scale prospective cohort study, the cognitive test that most
      strongly predicted future crashes would, if used as a screening tool, potentially
      prevent six crashes per 1000 people over 65 screened, but at the price of
      stopping the driving of 121 people who would not have had a crash. OBJECTIVES: 
      PRIMARY OBJECTIVES: 1. To assess whether driving assessment facilitates continued
      driving in people with dementia 2. To assess whether driving assessment reduces
      accidents in people with dementia. SECONDARY OBJECTIVE: To assess the quality of
      research on assessment of drivers with dementia. SEARCH STRATEGY: The Cochrane
      Dementia Group's Specialized Register was searched on 30 October 2007 using the
      terms: driving or driver* or "motor vehicle*" or "car accident*" or "traffic
      accident*" or automobile* or traffic. This register contains records from major
      healthcare databases, ongoing trial databases and grey literature sources and is
      updated regularly. SELECTION CRITERIA: We sought randomized controlled trials
      prospectively evaluating drivers with dementia for outcomes such as transport
      mobility, driving cessation or motor vehicle accidents following driving
      assessment. DATA COLLECTION AND ANALYSIS: Each author retrieved studies and
      assessed for primary and secondary outcomes, study design and study quality. MAIN
      RESULTS: No studies were found that met the inclusion criteria. A description and
      discussion of the driving literature relating to assessment of drivers with
      dementia relating to the primary objectives is presented. AUTHORS' CONCLUSIONS:
      In an area with considerable public health impact for drivers with dementia and
      other road users, the available literature fails to demonstrate the benefit of
      driver assessment for either preserving transport mobility or reducing motor
      vehicle accidents. Driving legislation and recommendations from medical
      practitioners requires further research that addresses these outcomes in order to
      provide the best outcomes for both drivers with dementia and the general public.

PMID- 19160271
TI  - Vision screening of older drivers for preventing road traffic injuries and
      fatalities.
AB  - BACKGROUND: Demographic data in North America, Europe, Asia, Australia and New
      Zealand suggest a rapid growth in the number of persons over the age of 65 years
      as the baby boomer generation passes retirement age. As older adults make up an
      increasing proportion of the population, they are an important consideration when
      designing future evidence-based traffic safety policies, particularly those that
      lead to restrictions or cessation of driving. Research has shown that cessation
      of driving among older drivers can lead to negative emotional consequences such
      as loss of independence and depression. Those older adults who continue to drive
      tend to do so less frequently than other demographic groups and are more likely
      to be involved in a road traffic crash, probably due to what is termed the 'low
      mileage bias'. There is universal agreement among researchers that vision plays a
      significant role in driving performance, and that there are age-related visual
      changes. Vision testing of all drivers, and in particular of older drivers, is
      therefore an important road safety issue. The components of visual function
      essential for driving are acuity, field, depth perception and contrast
      sensitivity, which are currently not fully measured by licensing agencies.
      Furthermore, it is not known how effective vision screening tools are, and
      current vision screening regulations and cut-off values required to pass a
      licensing test vary from country to country. There is, therefore, a need to
      develop evidence-based tools for vision screening for driving, thereby increasing
      road safety. OBJECTIVES: To assess the effects of vision screening interventions
      for older drivers to prevent road traffic injuries and fatalities. SEARCH
      STRATEGY: We searched the Cochrane Injuries Group Specialized Register, the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2006, issue 3), MEDLINE, EMBASE, TRANSPORT, AgeInfo, AgeLine, the National
      Research Register, the Science (and Social Science) Citation Index, IBSS
      (International Bibliography of Social Sciences), PsycINFO, and Zetoc. We also
      searched the Internet and checked the reference lists of relevant papers to
      identify any further studies. The searches were conducted up to September 2006.
      SELECTION CRITERIA: Randomized controlled trials (RCTs) and controlled before and
      after studies comparing vision screening to non-screening of drivers aged 55
      years and older, and which assessed the effect on road traffic crashes, injuries,
      fatalities and any involvement in traffic law violations, were included. DATA
      COLLECTION AND ANALYSIS: Two authors independently screened the reference lists
      for eligible articles and independently assessed the articles for inclusion
      against the criteria. Two authors independently extracted data using a
      standardized extraction form. MAIN RESULTS: No studies were found which met the
      inclusion criteria for this review. AUTHORS' CONCLUSIONS: Most countries require
      a vision screening test for the renewal of an individual's driver's license.
      There is, however, insufficient evidence to assess the effect of vision screening
      tests on subsequent motor vehicle crash reduction. There is a need to develop
      valid and reliable tools of vision screening that can predict driving
      performance.

PMID- 19160272
TI  - Interventions for pemphigus vulgaris and pemphigus foliaceus.
AB  - BACKGROUND: A range of interventions have been described for treatment of
      pemphigus, however the optimal therapeutic strategy has not been established.
      OBJECTIVES: To assess the efficacy and safety of all interventions used in the
      management of pemphigus vulgaris and pemphigus foliaceus. SEARCH STRATEGY: We
      searched the Cochrane Skin Group Specialised Register (October 2008), The
      Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4,
      2008), MEDLINE (2003 to October 2008), EMBASE (2005 to October 2008), LILACS
      (1981 to October 2008), Ongoing Trials Registers, reference lists of articles,
      conference proceedings from international pemphigus meetings and contacted
      experts in the field. SELECTION CRITERIA: Randomised controlled trials of any
      intervention in pemphigus vulgaris or pemphigus foliaceus. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed quality and extracted data from
      studies. All investigators were contacted for further information. Adverse events
      were identified from included studies. MAIN RESULTS: Eleven studies with a total
      of 404 participants (337 pemphigus vulgaris, 27 pemphigus foliaceus and 40 not
      specified ) were identified. The quality of included studies was not high, the
      majority of studies did not report allocation concealment, and power was limited
      by very small sample sizes. Interventions assessed included prednisolone dose
      regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine,
      dapsone, mycophenolate, plasma exchange, topical epidermal growth factor and
      traditional Chinese medicine. Ten studies included participants with newly
      diagnosed or newly active recurrent disease, and one trial included participants
      in maintenance phase.There was sufficient data for 4 meta-analyses, each pooling
      results of two studies only. For the majority of interventions, results were
      inconclusive. We found some interventions to be superior for certain outcomes,
      although we were unable to conclude which treatments are superior overall.
      Mycophenolate was more effective in achieving disease control than azathioprine
      (1 study; n=40; RR 0.72; 95% CI 0.52 to 0.99, NNT 3.7). There was evidence of a
      steroid-sparing benefit of azathioprine (1 study; n=57; MWD -3919 mg
      prednisolone; 95% CI -6712 to -1126) and cyclophosphamide (1 study; n=54; MWD 
      3355 mg prednisolone; 95% CI -6144 to -566) compared to glucocorticoids alone.
      Topical epidermal growth factor decreased time to control (1 study; n=20; HR
      2.35; 95% CI 1.62 to 3.41). AUTHORS' CONCLUSIONS: There is inadequate information
      available at present to ascertain the optimal therapy for pemphigus vulgaris or
      pemphigus foliaceus. Further research is required, especially to assess the
      optimal glucocorticoid dose, the role of adjuvant immunosuppressive medications,
      and long-term adverse events to improve harm:benefit analyses.

PMID- 19160273
TI  - Open versus laparoscopic (assisted) ileo pouch anal anastomosis for ulcerative
      colitis and familial adenomatous polyposis.
AB  - BACKGROUND: Restorative proctocolectomy with ileo pouch anal anastomosis (IPAA)
      is the main surgical treatment for patients with ulcerative colitis (UC) and
      familial adenomatous polyposis (FAP). With the advancements of minimal-invasive
      surgery this demanding operation is increasingly being performed
      laparoscopically. Therefore, the presumed benefits of the laparoscopic approach
      need to be systematically evaluated. OBJECTIVES: To compare the beneficial and
      harmful effects of laparoscopic versus open IPAA for patients with UC and FAP.
      SEARCH STRATEGY: We searched The Cochrane IBD/FBD Group Specialized Trial
      Register (April 2007), The Cochrane Library (Issue 1, 2007), MEDLINE (1990 to
      April 2007), EMBASE (1990 to April 2007), ISI Web of Knowledge (1990 to April
      2007) and the web casts of the American Society of Colon and Rectal Surgeons
      (ASCRS) (up to 2006) for all trials comparing open versus laparoscopic IPAA.
      SELECTION CRITERIA: All trials in patients with UC or FAP comparing any kind of
      laparoscopic IPAA versus open IPAA. No language limitations were applied. DATA
      COLLECTION AND ANALYSIS: Two authors independently performed selection of trials
      and data extraction. The methodological quality of all included trials was
      evaluated to assess bias risk. Analysis of RCTs and non-RCTs was performed
      separately. Analyses were based on the intention-to-treat principle. Authors were
      requested additional information in case of missing data. Sensitivity and
      subgroup analyses were performed if appropriate. MAIN RESULTS: Eleven trials
      included 607 patients of whom 253 (41%) in the laparoscopic IPAA group. Only one
      of the included trials was a randomised controlled trial. There were no
      significant differences in mortality or complications between the two groups.
      Reoperation and readmission rates were not significantly different. Operative
      time was significantly longer in the laparoscopic group both in the RCT and meta
      analysis of non-RCTs (weighted mean difference (WMD) 91 minutes; 95% Confidence
      Interval (CI) 53 to 130). There were no significant differences between the two
      groups regarding postoperative recovery parameters. Total incision length was
      significantly shorter in the laparoscopic group, while two trials evaluating
      cosmesis found significantly higher cosmesis scores in the laparoscopic group.
      Other long-term outcomes were poorly reported. AUTHORS' CONCLUSIONS: The
      laparoscopic IPAA is a feasible and safe procedure. Short-term advantages of the
      laparoscopic approach seem to be limited and their clinical significance is
      arguable. Large high-quality trials focusing on differences regarding specific
      postoperative complications, cosmesis, quality of life and costs are needed.

PMID- 19160274
TI  - Drug treatment for spinal muscular atrophy type I.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is caused by degeneration of anterior
      horn cells, which leads to progressive muscle weakness. Children with SMA type I
      will never be able to sit without support and usually die by the age of two
      years. There are no known efficacious drug treatments that influence the disease
      course. OBJECTIVES: To evaluate if drug treatment is able to slow or arrest the
      disease progression of SMA type I, and to assess if such therapy can be given
      safely. Drug treatment for SMA type II and III will be will be the topic of a
      separate Cochrane review. SEARCH STRATEGY: We searched the Cochrane Neuromuscular
      Disease Group Trials Register (September 30 2008, The Cochrane Library (Issue 3,
      2008), MEDLINE (January 1966 to June 2008), EMBASE (January 1980 to June 2008),
      ISI (January 1988 to June 2008), and ACP Journal Club (January 1991 to June
      2008). SELECTION CRITERIA: All randomized or quasi-randomized trials that
      examined the efficacy of drug treatment for SMA type 1 were sought. Participants
      had to fulfil clinical criteria and, in studies including genetic analysis to
      confirm the diagnosis, have a deletion or mutation of the SMN1 gene (5q11.2
      13.2)The primary outcome measure was to be time from birth until death or full
      time ventilation. Secondary outcome measures were to be development of rolling,
      sitting or standing within one year after the onset of treatment, and adverse
      events attributable to treatment during the trial period. DATA COLLECTION AND
      ANALYSIS: Two authors (WB and AV) independently reviewed and extracted data from
      all potentially relevant trials. For included studies pooled relative risks and
      pooled weighted standardized mean differences were to be calculated to assess
      treatment efficacy MAIN RESULTS: One small randomized-controlled study comparing
      riluzole treatment to placebo for SMA type 1 was identified and included in the
      review. Regarding the primary outcome measure three of seven children treated
      with riluzole were still alive at the age of 30, 48 and 64 months, whereas all
      three children in the placebo group died, but the difference was not
      statistically significant. Regarding the secondary outcome measures none of the
      patients in the riluzole or placebo group developed the ability to roll, sit or
      stand, and no adverse effects were observed. AUTHORS' CONCLUSIONS: No drug
      treatment for SMA type I has been proven to have significant efficacy.

PMID- 19160275
TI  - Drug treatment for spinal muscular atrophy types II and III.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is caused by degeneration of anterior
      horn cells, which leads to progressive muscle weakness. Children with SMA type II
      do not develop the ability to walk without support and have a shortened life
      expectancy, whereas children with SMA type III develop the ability to walk and
      have a normal life expectancy. There are no known efficacious drug treatments
      that influence the disease course of SMA. OBJECTIVES: To evaluate if drug
      treatment is able to slow or arrest the disease progression of SMA type II and
      III, and to assess if such therapy can be given safely. Drug treatment for SMA
      type I will be the topic of a separate Cochrane review. SEARCH STRATEGY: We
      searched the Cochrane Neuromuscular Disease Group Trials Register (September 30
      2008), The Cochrane Library (Issue 3, 2008), MEDLINE (January 1966 to June 2008),
      EMBASE (January 1980 to June 2008), ISI (January 1988 to June 2008), and ACP
      Journal Club (January 1991 to June 2008). SELECTION CRITERIA: We sought all
      randomized or quasi-randomized trials that examined the efficacy of drug
      treatment for SMA type II and III. Participants had to fulfil the clinical
      criteria and, in studies including genetic analysis to confirm the diagnosis,
      have a deletion or mutation of the SMN1 gene (5q11.2-13.2)The primary outcome
      measure was to be change in disability score within one year after the onset of
      treatment. Secondary outcome measures within one year after the onset of
      treatment were to be change in muscle strength, ability to stand or walk, change
      in quality of life, time from the start of treatment until death or full time
      ventilation, and adverse events attributable to treatment during the trial
      period. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed and
      extracted data from all potentially relevant trials. Pooled relative risks and
      pooled weighted standardized mean differences were to be calculated to assess
      treatment efficacy MAIN RESULTS: Four randomized placebo-controlled trials on
      treatment for SMA type II and III were found and included in the review. The
      treatments were creatine, phenylbutyrate, gabapentin and thyrotropin releasing
      hormone. None of these trials showed any effect on the outcome measures in
      patients with SMA type II and III. None of the patients in any of the four trials
      died or reached the state of full time ventilation and serious side effects were
      infrequent. AUTHORS' CONCLUSIONS: There is no proven efficacious drug treatment
      for SMA type II and III.

PMID- 19160276
TI  - Low glycaemic index, or low glycaemic load, diets for diabetes mellitus.
AB  - BACKGROUND: The aim of diabetes management is to normalise blood glucose levels,
      since improved blood glucose control is associated with reduction in development,
      and progression, of complications. Nutritional factors affect blood glucose
      levels, however there is currently no universal approach to the optimal dietary
      treatment for diabetes. There is controversy about how useful the glycaemic index
      (GI) is in diabetic meal planning. Improved glycaemic control through diet could
      minimise medications, lessen risk of diabetic complications, improve quality of
      life and increase life expectancy. OBJECTIVES: To assess the effects of low
      glycaemic index, or low glycaemic load, diets on glycaemic control in people with
      diabetes. SEARCH STRATEGY: We performed electronic searches of The Cochrane
      Library, MEDLINE, EMBASE and CINAHL with no language restriction. SELECTION
      CRITERIA: We assessed randomised controlled trials of four weeks or longer that
      compared a low glycaemic index, or low glycaemic load, diet with a higher
      glycaemic index, or load, or other diet for people with either type 1 or 2
      diabetes mellitus, whose diabetes was not already optimally controlled. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently extracted data on study
      population, intervention and outcomes for each included study, using standardised
      data extraction forms. MAIN RESULTS: Eleven relevant randomised controlled trials
      involving 402 participants were identified. There was a significant decrease in
      the glycated haemoglobin A1c (HbA1c) parallel group of trials, the weighted mean
      difference (WMD) was -0.5% with a 95% confidence interval (CI) of - 0.9 to -0.1,
      P = 0.02; and in the cross-over group of trials the WMD was -0.5% with a 95% CI
      of -1.0 to -0.1, P = 0.03. Episodes of hypoglycaemia were significantly fewer
      with low compared to high GI diet in one trial (difference of -0.8 episodes per
      patient per month, P < 0.01), and proportion of participants reporting more than
      15 hyperglycaemic episodes per month was lower for low-GI diet compared to
      measured carbohydrate exchange diet in another study (35% versus 66%, P = 0.006).
      No study reported on mortality, morbidity or costs. AUTHORS' CONCLUSIONS: A low
      GI diet can improve glycaemic control in diabetes without compromising
      hypoglycaemic events.

PMID- 19160277
TI  - Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease.
AB  - BACKGROUND: The anti-inflammatory effects of n-3 (omega-3 fatty acids, fish oil)
      have been suggested to be beneficial in chronic inflammatory disorders such as
      inflammatory bowel disease. OBJECTIVES: To systematically review the efficacy and
      safety of n-3 for maintenance of remission in Crohn's disease (CD). SEARCH
      STRATEGY: The following databases were searched from their inception without
      language restriction: Cochrane Central Register of Controlled Trials, MEDLINE,
      EMBASE, Healthstar, PubMed, and ACP journal club. Experts were contacted for
      unpublished data. SELECTION CRITERIA: Randomized placebo-controlled trials (RCT)
      of n-3 for maintenance of remission in CD were included. Studies must have
      enrolled patients of any age group, who were in remission at the time of
      recruitment, and were followed for at least six months. The intervention must
      have been fish oil or n-3 given in pre-defined dosage. Co-interventions were
      allowed only if they were balanced between the study groups. The primary outcome
      was the relapse rate and secondary outcomes included change in disease activity
      scores, time to first relapse and adverse events. DATA COLLECTION AND ANALYSIS:
      Two independent investigators reviewed studies for eligibility, extracted the
      data and assessed study quality using Jadad's criteria. Meta-analyses were
      performed using RevMan 4.2 software weighted by the Mantel-Haenszel method.
      Random or fixed effect models were used according to degree of heterogeneity and
      subgroup analyses were performed in an attempt to explore possible sources of
      heterogeneity. MAIN RESULTS: Six studies were eligible for inclusion. There was a
      marginal significant benefit of n-3 therapy for maintaining remission (RR 0.77
      0.; 95%CI 0.61 to 0.98; P = 0.03). However, the studies were both clinically and
      statistically heterogeneous (P = 0.03, I(2) = 58%). Two large studies showed
      negative results. When considering the estimated rather than the observed 1-year
      relapse rate of these two studies, the benefit was no longer statistically
      significant (RR 0.59; 95% CI 0.34 to 1.03; P=0.06). A funnel plot suggested
      publication bias. No serious adverse events were recorded in any of the studies
      but in a pooled analyses there was a significantly higher rate of diarrhea (RR
      1.36 95% CI 1.01 to 1.84) and symptoms of the upper gastrointestinal tract (RR
      1.98 95% CI 1.38 to 2.85) in the n-3 treatment group. AUTHORS' CONCLUSIONS: Omega
      3 fatty acids are safe but probably ineffective for maintenance of remission in
      CD. The existing data do not support routine maintenance treatment of Crohn's
      disease with omega 3 fatty acids.

PMID- 19160278
TI  - Methotrexate for high-grade osteosarcoma in children and young adults.
AB  - BACKGROUND: The majority of the currently used treatment protocols for
      osteosarcoma are based on a combination of doxorubicin, cisplatin, methotrexate
      (MTX) and/or ifosfamide, of which MTX seems to be one of the most active drugs.
      However, in the literature, this has not been unambiguously proven. OBJECTIVES:
      To compare the effectiveness of treatment including MTX with treatment without
      MTX for children and young adults (up to 21 years) with primary high-grade
      osteosarcoma. SEARCH STRATEGY: We searched the Cochrane Central Register of
      Controlled Trials (The Cochrane Library, issue 3, 2008), MEDLINE (1966 to July
      2008) and EMBASE (1980 to July 2008). In addition, we searched reference lists of
      relevant articles, conference proceedings and ongoing trials databases. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials
      (CCTs) comparing the effectiveness of treatment including MTX with treatment
      without MTX in the treatment of paediatric high-grade osteosarcoma. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently performed the study
      selection. One reviewer performed the data extraction and quality assessment,
      which was checked by another reviewer. MAIN RESULTS: We could not identify any
      studies in which the only difference between the treatment groups was the use of
      MTX.We did identify a RCT comparing MTX with cisplatin (n=30 children). The risk
      of bias in this study was difficult to assess due to a lack of reporting.
      Survival could not be evaluated, but no evidence of a significant difference in
      response rate between the treatment groups was identified (RR=0.44; 95% CI 0.17
      to 1.13; P=0.09). A significant difference in the occurrence of toxicities in
      favour of MTX was identified, but with regard to quality of life treatment with
      cisplatin seemed to give better results.For other combinations of treatment
      including and not including MTX no studies were identified. AUTHORS' CONCLUSIONS:
      Since no RCTs or CCTs in which only the use of MTX differed between the treatment
      groups were identified, no definitive conclusions can be made about the effects
      on antitumour efficacy, toxicities and quality of life of the addition of MTX to
      treatment of children and young adults with primary high-grade osteosarcoma. The
      same is true for combinations of treatment including and not including MTX other
      than treatment with MTX versus treatment with cisplatin. Only 1 RCT comparing MTX
      with cisplatin treatment was available and therefore, no definitive conclusions
      can be made about the effectiveness of these agents in children and young adults
      with primary high-grade osteosarcoma. Furthermore, this study was performed in a
      different treatment era. Nowadays single agent treatment of osteosarcoma is
      considered inadequate. Based on the currently available evidence, we are not able
      to give recommendations for the use of MTX in clinical practice. More high
      quality research is needed.

PMID- 19160279
TI  - Sedation versus general anaesthesia for provision of dental treatment in under 18
      year olds.
AB  - BACKGROUND: A significant proportion of children have caries requiring
      restorations or extractions, and some of these children will not accept this
      treatment under local anaesthetic. Historically this has been managed in children
      by use of a general anaesthetic; however use of sedation may lead to reduced
      morbidity and cost. The aim of this review is to compare the efficiency of
      sedation versus general anaesthesia for the provision of dental treatment for
      children and adolescents under 18 years. OBJECTIVES: We evaluated the intra- and
      post-operative morbidity, effectiveness and cost effectiveness of sedation versus
      general anaesthesia for the provision of dental treatment for under 18 year olds.
      SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library; Issue 4, 2008); MEDLINE (OVID) (1950 to October
      Week 2, 2008); EMBASE (OVID) (1974 to Week 42, 2008); System for information on
      Grey Literature in Europe (SIGLE) (1980 to October 2008), Latin American &
      Caribbean Health Sciences Literature (LILACS) (1982 to October 2008), ISI Web of
      Science (1945 to October 2008).We also carried out handsearching of relevant
      journals. There was no language restriction. SELECTION CRITERIA: We included
      randomized controlled clinical trials of sedative agents compared to general
      anaesthesia in children and adolescents aged up to 18 years having dental
      treatment. We excluded complex surgical procedures and pseudo-randomized trials.
      DATA COLLECTION AND ANALYSIS: Two authors assessed titles and abstracts for
      inclusion in the review. We recorded information relevant to the objectives and
      outcome measures into a specially designed 'data extraction form'. MAIN RESULTS:
      We identified 15 studies for potential inclusion after searching the available
      databases and screening the titles and abstracts. We identified a further study
      through personal contacts. Following full text retrieval of the studies, we found
      none to be eligible AUTHORS' CONCLUSIONS: Randomized controlled studies comparing
      the use of dental general anaesthesia with sedation to quantify differences such
      as morbidity and cost are required.

PMID- 19160280
TI  - Benzodiazepines for delirium.
AB  - BACKGROUND: Delirium occurs in 30% of hospitalised patients and is associated
      with prolonged hospital stay and increased morbidity and mortality. The results
      of uncontrolled studies have been unclear, with some suggesting that
      benzodiazepines may be useful in controlling non-alcohol related delirium.
      OBJECTIVES: To determine the effectiveness and incidence of adverse effects of
      benzodiazapines in the treatment of non-alcohol withdrawal related delirium.
      SEARCH STRATEGY: The trials were identified from a search of the Specialized
      Register of the Cochrane Dementia and Cognitive Improvement Group on 26 February
      2008 using the search terms: (deliri* or confusion) and (benzo* or lorazepam," or
      "alprazolam" or "ativan" or diazepam or valium or chlordiazepam).The CDCIG
      Specialized Register contains records from major health databases (including
      MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL, LILACS) as well as many ongoing trial
      databases and grey literature sources. SELECTION CRITERIA: Trials had to be
      unconfounded, randomized and with concealed allocation of subjects. Additionally,
      selected trials had to have assessed patients pre- and post-treatment. Where
      crossover design was present, only data from the first part of the trial were to
      be examined. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data from
      included trials. Data were pooled where possible, and were to be analysed using
      appropriate statistical methods. Odd ratios or average differences were to be
      calculated. Only "intention to treat" data were to be included. MAIN RESULTS:
      Only one trial satisfying the selection criteria could be identified. In this
      trial, comparing the effect of the benzodiazepine, lorazepam, with
      dexmedetomidine, a selective alpha-2-adrenergic receptor agonist, on delirium
      among mechanically ventilated intensive care unit patients, dexmedetomidine
      treatment was associated with an increased number of delirium- and coma-free days
      compared with lorazepam treated patients (dexmedetomidine patients, average seven
      days; lorazepam patients, average three days; P = 0.01). One partially controlled
      study showed no advantage of a benzodiazepine (alprazolam) compared with
      neuroleptics in treating agitation associated with delirium, and another
      partially controlled study showed decreased effectiveness of a benzodiazepine
      (lorazepam), and increased adverse effects, compared with neuroleptics
      (haloperidol, chlorpromazine) for the treatment of acute confusion. AUTHORS'
      CONCLUSIONS: No adequately controlled trials could be found to support the use of
      benzodiazepines in the treatment of non-alcohol withdrawal related delirium among
      hospitalised patients, and at this time benzodiazepines cannot be recommended for
      the control of this condition. Because of the scarcity of trials with
      randomization of patients, placebo control, and adequate concealment of
      allocation of subjects, it is clear that further research is required to
      determine the role of benzodiazepines in the treatment of non-alcohol withdrawal
      related delirium.

PMID- 19160281
TI  - Dietary interventions for rheumatoid arthritis.
AB  - BACKGROUND: The question of what potential benefits and harms are associated with
      certain dietary regimes used in rheumatoid arthritis is an important one for many
      patients and health care providers. OBJECTIVES: To assess the effectiveness and
      safety of dietary interventions in the treatment of rheumatoid arthritis. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL)(The Cochrane Library, issue 1 2008), MEDLINE, EMBASE, AMED, CINAHL and
      reference lists of relevant articles (up to January 2008), and contacted authors
      of included articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) or
      controlled clinical trials (CCTs) where the effectiveness of dietary manipulation
      was evaluated. Dietary supplement studies (including fish oil supplements) were
      not included. DATA COLLECTION AND ANALYSIS: Two authors independently selected
      trials for inclusion, assessed the internal validity of included trials and
      extracted data. Investigators were contacted to obtain missing information. MAIN
      RESULTS: Fourteen RCTs and one CCT, with a total of 837 patients, were included.
      Due to heterogeneity of interventions and outcomes, baseline imbalance and
      inadequate data reporting, no overall effects were calculated. A single trial
      with a moderate risk of bias found that fasting, followed by 13 months on a
      vegetarian diet, may reduce pain (mean difference (MD) on a 0 to 10 scale -1.89,
      95% confidence interval (CI) -3.62 to -0.16), but not physical function or
      morning stiffness immediately after intervention. Another single trial with a
      moderate risk of bias found that a 12-week Cretan Mediterranean diet may reduce
      pain (MD on a 0 to 100 scale -14.00, 95% CI -23.6 to -4.37), but not physical
      function or morning stiffness immediately after intervention. Two trials compared
      a 4-week elemental diet with an ordinary diet and reported no significant
      differences in pain, function or stiffness. Due to inadequate data reporting, the
      effects of vegan and elimination diets are uncertain. When comparing any dietary
      manipulation with an ordinary diet we found a significantly higher total drop-out
      of 10% (risk difference (RD) 0.10, 95% CI 0.02 to 0.18), higher treatment-related
      drop-out of 5% (RD 0.05, 95% CI -0.03 to 0.14) and a significantly higher weight
      loss (weighted mean difference -3.23, 95% CI -4.79 to -1.67 kg) in the diet
      groups compared to the control groups. AUTHORS' CONCLUSIONS: The effects of
      dietary manipulation, including vegetarian, Mediterranean, elemental and
      elimination diets, on rheumatoid arthritis are still uncertain due to the
      included studies being small, single trials with moderate to high risk of bias.
      Higher drop-out rates and weight loss in the groups with dietary manipulation
      indicate that potential adverse effects should not be ignored.

PMID- 19160282
TI  - Bone marrow harvest versus peripheral stem cell collection for haemopoietic stem
      cell donation in healthy donors.
AB  - BACKGROUND: Haemopoietic stem cells can be collected from a donor either as a
      bone marrow harvest or by peripheral blood collection. Both techniques have risks
      for the donor. OBJECTIVES: The aim of this review was to identify the adverse
      effects of haemopoietic stem cell donation and to compare the tolerability and
      safety of the two methods. SEARCH STRATEGY: We searched bibliographic databases
      including the Cochrane Central Register of Controlled trials (CENTRAL) (The
      Cochrane Library 2008, issue 2), MEDLINE and EMBASE up to May 2008. We also
      searched reference lists of articles and contacted experts in the field.
      SELECTION CRITERIA: Randomised controlled trials enrolling haemopoietic stem cell
      donors and evaluating the different methods of donating haemopoietic stem cells
      were eligible. DATA COLLECTION AND ANALYSIS: Two authors independently screened
      studies for inclusion. We extracted data and evaluated methodological quality.
      Quantitative analysis was not possible for most outcomes, but where used we
      preferred random-effects models due to the variability between the included
      studies. MAIN RESULTS: Six trials (807 donors) were eligible: all were
      substudies, or constituent parts of, larger randomised controlled trials of bone
      marrow and peripheral blood stem cell allogeneic transplantation. No included
      trial was designed solely to measure and assess the experience of stem cell
      donors. The donors in all studies were related to the stem cell recipient.
      Overall, both types of donors experienced pain subsequent to donation, and
      psychological morbidity. The trend was for bone marrow donors to experience more
      pain at the donation site, more overall adverse events, and more days of
      restricted activity. They were also more likely to require hospitalisation than
      peripheral blood stem cell donors. In contrast, peripheral blood stem cell donors
      experienced more pain prior to donation, which may be related to the pre-donation
      administration of granulocyte colony stimulating factor (G-CSF). The
      methodological quality of the studies was poor and indicated limitations due to
      the risk of selection and attrition bias. The proportion of donors from the
      parent trial not included in the donor substudies was also inadequately
      explained. AUTHORS' CONCLUSIONS: The different short-term morbidities associated
      with each type of haemopoietic stem cell donation were clear, with bone marrow
      donors experiencing more pain and more restriction post-donation than peripheral
      blood donors. However, the studies were limited by their methodological quality,
      failure to provide long-term follow up (for which larger numbers of donors would
      be required) and a failure to apply consistent measures of quality of life in a
      way which allows more meaningful evaluation across studies.

PMID- 19160283
TI  - WITHDRAWN: Methods of vascular occlusion for elective liver resections.
AB  - BACKGROUND: Vascular occlusion is used to reduce blood loss during liver
      resection surgery. There is considerable controversy regarding whether vascular
      occlusion should be used or not during elective liver resections. The method of
      vascular occlusion employed is also controversial. There is also considerable
      debate on the role of ischaemic preconditioning before vascular occlusion.
      OBJECTIVES: To assess the advantages (decreased blood loss and peri-operative
      morbidity) and disadvantages (liver dysfunction from ischaemia) of vascular
      occlusion during liver resections. To compare the advantages (in decreasing blood
      loss or decreasing ischaemia-reperfusion injury) and disadvantages of different
      types of vascular occlusion versus total, continuous portal triad clamping.
      SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The
      Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until
      March 2007. SELECTION CRITERIA: We included randomised clinical trials comparing
      vascular occlusion versus no vascular occlusion during elective liver resections
      (irrespective of language or publication status). We also included randomised
      clinical trials comparing the different methods of vascular occlusion and those
      investigating the role of ischaemic preconditioning in liver resection. DATA
      COLLECTION AND ANALYSIS: We collected the data on the characteristics of the
      trial, methodological quality of the trials, mortality, morbidity, blood loss,
      blood transfusion requirements, liver function tests, markers of neutrophil
      activation, operating time, and hospital stay. We analysed the data with both the
      fixed-effect and the random-effects models using RevMan Analysis. For each binary
      outcome we calculated the odds ratio (OR) with 95% confidence intervals (CI)
      based on intention-to-treat analysis. For continuous outcomes, we calculated the
      weighted mean difference (WMD) with 95% confidence intervals. MAIN RESULTS: We
      identified a total of 16 randomised trials. Five trials including 331 patients
      compared vascular occlusion (n = 166) versus no vascular occlusion (n = 165). Six
      trials including 521 patients compared different methods of vascular occlusion.
      Three trials including 210 patients compared ischaemic preconditioning before
      continuous portal triad clamping (n = 105) versus no ischaemic preconditioning (n
      = 105). Two trials including 127 patients compared ischaemic preconditioning
      before continuous portal triad clamping (n = 63) versus intermittent portal triad
      clamping (n = 64).The blood loss was significantly lower in vascular occlusion
      compared with no vascular occlusion. The liver enzymes were significantly
      elevated in the vascular occlusion group compared with no vascular occlusion.
      There was no difference in the mortality, liver failure, or other morbidities.
      Four of the five trials comparing vascular occlusion and no vascular occlusion
      used intermittent vascular occlusion. Trials comparing complete inflow and
      outflow occlusion to the liver, ie, hepatic vascular exclusion and portal triad
      clamping demonstrate significant detrimental haemodynamic changes in hepatic
      vascular exclusion compared to portal triad clamping. There was no significant
      difference in the number of units transfused and the number of patients needing
      transfusion. There was no difference in mortality, liver failure, or morbidity
      between total and selective methods of portal triad clamping. All four cases of
      mortality and liver failure in the comparison between the intermittent and
      continuous portal triad clamping occurred in the continuous portal triad clamping
      (statistically not significant). Intermittent portal triad clamping does not
      increase the total blood loss or operating time compared to continuous portal
      triad clamping.There was no statistically significant difference in the
      mortality, liver failure, morbidity, blood loss, or haemodynamic changes between
      ischaemic preconditioning versus no ischaemic preconditioning before continuous
      portal triad clamping. Liver enzymes used as markers of liver injury were
      significantly lower in the early post-operative period in the ischaemic
      preconditioning group. The intensive therapy unit stay and hospital stay were
      statistically significantly lower in the ischaemic preconditioning group than in
      the no ischaemic preconditioning group.There was no statistically significant
      difference in the mortality, liver failure, morbidity, intensive therapy unit
      stay, or hospital stay between ischaemic preconditioning before continuous portal
      triad clamping and intermittent portal triad clamping. The blood loss and
      transfusion requirements were lower in the ischaemic preconditioning group.
      Aspartate aminotransferase level was lower in the intermittent portal triad
      clamping group than the ischaemic preconditioning group on the third post
      operative day. There was no difference in the peak aspartate aminotransferase
      levels or in the aspartate aminotransferase levels on first or sixth post
      operative days of aspartate aminotransferase . AUTHORS' CONCLUSIONS: Intermittent
      vascular occlusion seems safe in liver resection. However, it does not seem to
      decrease morbidity. Among the different methods of vascular occlusion,
      intermittent portal triad clamping has most evidence to support the clinical
      application. Hepatic vascular exclusion cannot be recommended routinely.
      Ischaemic preconditioning before continuous portal triad clamping may be of
      clinical benefit in reducing intensive therapy unit and hospital stay.

PMID- 19160284
TI  - Chinese herbal medicine for premenstrual syndrome.
AB  - BACKGROUND: Traditional Chinese herbal medicines are frequently used to treat
      premenstrual syndrome (PMS) in China. Until now, their efficacy has not been
      systematically reviewed. OBJECTIVES: To evaluate the effectiveness and safety of
      traditional Chinese herbal medicines in the treatment of women with premenstrual
      syndrome. SEARCH STRATEGY: We searched MEDLINE (January 1950 to December, 2007),
      EMBASE (January 1980 to December, 2007), Chinese Biomedical Database (CBM)
      (January 1975 to December, 2007), China National Knowledge Infrastructure (CNKI)
      (January 1994 to December, 2007), and the VIP Database (January 1989 to December,
      2007). SELECTION CRITERIA: Randomised controlled trials (RCTs) studying the
      efficacy of traditional Chinese herbal medicine(s) for treatment of the
      premenstrual syndrome were included. DATA COLLECTION AND ANALYSIS: Two review
      authors telephoned the original authors of the RCTs to confirm the randomisation
      procedure, extracted and analysed data from the trials that met the inclusion
      criteria. MAIN RESULTS: Two RCT considering 549 women were included. One trial
      which was identified to be of higher methodological quality demonstrated the
      therapeutic effectiveness of Jingqianping granule. The other study was considered
      of lower quality due to the inherent risk of various biases in it. Two studies
      showed statistically significant differences in elimination of symptoms in
      proliferative phase and premenstrual phase by taking Jingqianping granule than
      taking Xiaoyaowan (RR 3.50, 95% CI1.74 to 7.06). Women treated by Cipher
      decoction had a higher rate of recovery than those taking Co-vitamin B6 capsules
      (RR 48.99, 95% CI 3.06 to 783.99). AUTHORS' CONCLUSIONS: It is rare in PMS
      management that efficacy claims are substantiated by clinical trials. One of the
      identified trials was well designed and reported on the effectiveness of
      Jingqianping in the treatment of premenstrual syndrome Qiao 2002. However,
      currently there is insufficient evidence to support the use of chinese herbal
      medicine for PMS and further, well controlled, trials are needed before any final
      conclusions could be drawn.

PMID- 19160285
TI  - Impact of tuberculosis preventive therapy on tuberculosis and mortality in HIV
      infected children.
AB  - BACKGROUND: Children with HIV are at increased risk of acquiring tuberculosis
      (TB), a common cause of acute and chronic respiratory disease and death in HIV
      infected children living in areas where prevalence of the disease is high.
      Children infected with HIV and TB have worse outcomes than HIV-uninfected
      children who have TB; thus, preventing the infection and disease in HIV-infected
      children is potentially an important public health intervention. Isoniazid, an
      anti-tuberculosis medication, has been used effectively to prevent TB in HIV
      uninfected children, but currently there are no guidelines on the use of TB
      preventive therapy in HIV-infected children. OBJECTIVES: To determine the impact
      of TB preventive therapy on TB-related incidence and death in HIV-infected
      children SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register
      (CENTRAL/CCTR), Cochrane HIV/AIDS Group Specialized Register, MEDLINE/PubMed,
      EMBASE, and AIDSearch. In addition, we scanned reference lists, manually searched
      conference abstracts, and contacted content experts. SELECTION CRITERIA: We
      included studies of HIV-infected children randomised to receive TB preventive
      therapy or placebo, or an alternative TB preventive regimen. Participants could
      have tuberculin skin test results that were positive or negative. DATA COLLECTION
      AND ANALYSIS: Two authors independently used the study selection criteria,
      assessed methodological quality and extracted data. Effects were assessed using
      hazard ratios. MAIN RESULTS: One trial met the selection criteria for the review.
      The trial participants were HIV-infected children, most of whom were not taking
      antiretroviral therapy. Subjects were randomised to isoniazid and cotrimoxazole
      or placebo and cotrimoxazole, given daily or three times a week. The trial showed
      a marked reduction in TB incidence and death in the isoniazid group. As yet,
      however, there are no long-term follow-up data on the durability of the
      protective effect or on possible long-term adverse events. This trial also was
      unable to assess the impact of isoniazid prophylaxis on children receiving
      antiretroviral therapy. AUTHORS' CONCLUSIONS: Isoniazid prophylaxis in HIV
      infected children has the potential to play a major public health role by
      reducing TB incidence and death. As yet, however, data are insufficient to guide
      the duration of prophylaxis and to support its use in children using highly
      active antiretroviral therapy (HAART) and in those living in areas of low TB
      prevalence. Further studies are needed to assess whether TB preventive therapy is
      of benefit in all HIV-infected children, irrespective of use of antiretroviral
      treatment, the optimal duration of preventive therapy, or long-term adverse
      events.

PMID- 19160286
TI  - Psychological treatments for the management of irritable bowel syndrome.
AB  - BACKGROUND: No consensus exists on the optimal treatment for irritable bowel
      syndrome (IBS). Psychological treatments are increasingly advocated but their
      effectiveness is unclear. OBJECTIVES: To evaluate the efficacy of psychological
      interventions for the treatment of irritable bowel syndrome. SEARCH STRATEGY: A
      computer assisted search of MEDLINE, EMBASE, PsychInfo, CINAHL, Web of Science,
      The Cochrane Library and Google Scholar was performed for the years 1966-2008.
      Local databases were searched in Europe. SELECTION CRITERIA: Randomised trials
      comparing single psychological interventions with either usual care or mock
      interventions in patients over 16 years of age. No language criterion was
      applied. DATA COLLECTION AND ANALYSIS: The search identified 25 studies that
      fulfilled the inclusion criteria. The relative risk (RR), risk difference (RD),
      number needed to treat (NNT) and standardized mean difference (SMD) along with
      95% confidence intervals were calculated using a random effects model for each
      outcome. MAIN RESULTS: Psychological interventions as a group The SMD for symptom
      score improvement at 2 and 3 months was 0.97 (95% CI 0.29 to 1.65) and 0.62 (95%
      CI 0.45 to 0.79) respectively compared to usual care. Against placebo, the SMDs
      were 0.71 (95% CI 0.08 to 1.33) and -0.17 (95% CI -0.45 to 0.11) respectively.
      For improvement of abdominal pain, the SMDs at 2 and 3 months were 0.54 (95%CI
      0.10 to 0.98) and 0.26 (95% CI 0.07 to 0.45) compared to usual care. The SMD from
      placebo at 3 months was 0.31 (95% CI -0.16 to 0.79). For improvement in quality
      of life, the SMD from usual care at 2 and 3 months was 0.47 (95%CI 0.11 to 0.84)
      and 0.31 (95%CI -0.16 to 0.77) respectively. Cognitive behavioural therapy The
      SMD for symptom score improvement at 2 and 3 months was 0.75 (95% CI -0.20 to
      1.70) and 0.58 (95% CI 0.36 to 0.79) respectively compared to usual care. Against
      placebo, the SMDs were 0.68 (95% CI -0.01 to 1.36) and -0.17 (95% CI -0.45 to
      0.11) respectively. For improvement of abdominal pain, the SMDs at 2 and 3 months
      were 0.45 (95% CI 0.00 to 0.91) and 0.22 (95% CI -0.04 to -0.49) compared to
      usual care. Against placebo the SMD at 3 months was 0.33 (95% CI -0.16 to 0.82).
      For improvement in quality of life, the SMDs at 2 and 3 months compared to usual
      care were 0.44 (95% CI 0.04 to 0.85) and 0.92 (95% CI 0.07 to 1.77)
      respectively.Interpersonal psychotherapy The RR for adequate relief of symptoms
      was 2.02 (95% CI 1.13 to 3.62), RD 0.30 (95% CI 0.13 to 0.46), NNT 4 for
      comparison with care as usual. The SMD for improvement of symptom score was 0.35
      (95% CI -0.75 to 0.05) compared with usual care. Relaxation/Stress management The
      SMD in symptom score improvement at 2 months was 0.50 (95%CI 0.02 to 0.98)
      compared with usual care. The SMD in improvement of abdominal pain at 3 months
      was 0.02 (95%CI -0.56 to 0.61) compared with usual care. Long term results Very
      few long term follow-up results were available. There was no convincing evidence
      that treatment effects were sustained following completion of treatment for any
      treatment modality. AUTHORS' CONCLUSIONS: Psychological interventions may be
      slightly superior to usual care or waiting list control conditions at the end of
      treatment although the clinical significance of this is debatable. Except for a
      single study, these therapies are not superior to placebo and the sustainability
      of their effect is questionable. The meta-analysis was significantly limited by
      issues of validity, heterogeneity, small sample size and outcome definition.
      Future research should adhere to current recommendations for IBS treatment trials
      and should focus on the long-term effects of treatment.

PMID- 19160287
TI  - Kinship care for the safety, permanency, and well-being of children removed from
      the home for maltreatment.
AB  - BACKGROUND: Every year a large number of children around the world are removed
      from their homes because they are maltreated. Child welfare agencies are
      responsible for placing these children in out-of-home settings that will
      facilitate their safety, permanency, and well-being. However, children in out-of
      home placements typically display more educational, behavioral, and psychological
      problems than do their peers, although it is unclear whether this results from
      the placement itself, the maltreatment that precipitated it, or inadequacies in
      the child welfare system. OBJECTIVES: To evaluate the effect of kinship care
      placement on the safety, permanency, and well-being of children removed from the
      home for maltreatment. SEARCH STRATEGY: The following databases were searched to
      Februrary 2007: CENTRAL, MEDLINE, C2- Specter, Sociological Abstracts, Social
      Work Abstracts, SSCI, Family and Society Studies Worldwide, ERIC, PsycINFO, ISI
      Proceedings, CINAHL, ASSIA, and Dissertation Abstracts International. Relevant
      social work journals and reference lists of published literature reviews were
      handsearched, and authors contacted. SELECTION CRITERIA: Randomized experimental
      and quasi-experimental studies, in which children removed from the home for
      maltreatment and subsequently placed in kinship foster care, were compared with
      children placed in non-kinship foster care on child welfare outcomes in the
      domains of well-being, permanency, or safety. DATA COLLECTION AND ANALYSIS:
      Reviewers independently read the titles and abstracts identified in the search
      and selected appropriate studies. Reviewers assessed the eligibility of each
      study for the evidence base and then evaluated the methodological quality of the
      included studies. Lastly, outcome data were extracted and entered into REVMAN for
      meta-analysis with the results presented in written and graphical forms. MAIN
      RESULTS: Sixty two quasi-experimental studies were included in this review. Data
      suggest that children in kinship foster care experience better behavioral
      development, mental health functioning, and placement stability than do children
      in non-kinship foster care. Although there was no difference on reunification
      rates, children in non-kinship foster care were more likely to be adopted while
      children in kinship foster care were more likely to be in guardianship. Lastly,
      children in non-kinship foster care were more likely to utilize mental health
      services. AUTHORS' CONCLUSIONS: This review supports the practice of treating
      kinship care as a viable out-of-home placement option for children removed from
      the home for maltreatment. However, this conclusion is tempered by the pronounced
      methodological and design weaknesses of the included studies.

PMID- 19160288
TI  - Virtual reality training for surgical trainees in laparoscopic surgery.
AB  - BACKGROUND: Surgical training has traditionally been one of apprenticeship, where
      the surgical trainee learns to perform surgery under the supervision of a trained
      surgeon. This is time consuming, costly, and of variable effectiveness. Training
      using a virtual reality simulator is an option to supplement standard training.
      OBJECTIVES: To determine whether virtual reality training can supplement or
      replace conventional laparoscopic surgical training (apprenticeship) in surgical
      trainees with limited or no prior laparoscopic experience. SEARCH STRATEGY: We
      searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the
      Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library,
      MEDLINE, EMBASE, Science Citation Index Expanded, and grey literature until March
      2008. SELECTION CRITERIA: We included all randomised clinical trials comparing
      virtual reality training versus other forms of training including video trainer
      training, no training, or standard laparoscopic training in surgical trainees
      with little or no prior laparoscopic experience. We also included trials
      comparing different methods of virtual reality training. DATA COLLECTION AND
      ANALYSIS: We collected the data on the characteristics of the trial,
      methodological quality of the trials, mortality, morbidity, conversion rate,
      operating time, and hospital stay. We analysed the data with both the fixed
      effect and the random-effects models using RevMan Analysis. For each outcome we
      calculated the standardised mean difference with 95% confidence intervals based
      on intention-to-treat analysis. MAIN RESULTS: We included 23 trials with 612
      participants. Four trials compared virtual reality versus video trainer training.
      Twelve trials compared virtual reality versus no training or standard
      laparoscopic training. Four trials compared virtual reality, video trainer
      training and no training, or standard laparoscopic training. Three trials
      compared different methods of virtual reality training. Most of the trials were
      of high risk of bias. In trainees without prior surgical experience, virtual
      reality training decreased the time taken to complete a task, increased accuracy,
      and decreased errors compared with no training; virtual reality group was more
      accurate than video trainer training group. In the participants with limited
      laparoscopic experience, virtual reality training reduces operating time and
      error better than standard in the laparoscopic training group; composite
      operative performance score was better in the virtual reality group than in the
      video trainer group. AUTHORS' CONCLUSIONS: Virtual reality training can
      supplement standard laparoscopic surgical training of apprenticeship and is at
      least as effective as video trainer training in supplementing standard
      laparoscopic training. Further research of better methodological quality and more
      patient-relevant outcomes are needed.

PMID- 19160289
TI  - Robot assistant for laparoscopic cholecystectomy.
AB  - BACKGROUND: The role of a robotic assistant in laparoscopic cholecystectomy is
      controversial. While some trials have shown distinct advantages of robotic
      assistant over a human assistant, others have not, and it is unclear which
      robotic assistant is best. OBJECTIVES: The aims of this review are to compare the
      safety of robot assistant versus human assistant in laparoscopic cholecystectomy
      and to assess whether the robot can substitute for the human assistant. SEARCH
      STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The
      Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until May
      2008 for identifying the randomised trials using The Cochrane Hepato-Biliary
      Group search strategy. SELECTION CRITERIA: Only randomised clinical trials
      (irrespective of language, blinding, or publication status) comparing robot
      assistants versus human assistants in laparoscopic cholecystectomy were
      considered for the review. Randomised clinical trials comparing different types
      of robot assistants were also considered for the review. DATA COLLECTION AND
      ANALYSIS: Two authors independently identified the trials for exclusion and
      independently extracted the data. We calculated the risk ratio, mean difference,
      or standardised mean difference with 95% confidence intervals using the fixed
      effect and the random-effects models based on available case-analysis using
      RevMan 5. MAIN RESULTS: We included five trials (all of high risk of bias) with
      453 patients randomised: 159 to the robot-assistant group and 165 to the human
      assistant group (one trial report of 129 patients was a conference abstract, not
      reporting on the number of patients in each group). There was no statistically
      significant difference between the two groups for morbidity, conversion to open
      cholecystectomy, total operating time, or hospital stay when fixed-effect or
      random-effects model were used. The instrument set-up time was significantly
      lower in the human assistant group. In one trial, about one sixth of the
      laparoscopic cholecystectomies in which robot assistant was used, required
      temporary use of a human assistant. It appears that there was little or no
      requirement for human assistants in the other three published trials. In two of
      the three trials, which reported surgeons' preference, the surgeons preferred a
      robot assistant to a human assistant. There was no statistically significant
      difference in the accuracy when the random-effects model was used. There was no
      difference in the errors. AUTHORS' CONCLUSIONS: Although robot-assisted
      laparoscopic cholecystectomy appears safe, there seems to be no significant
      advantages over human-assisted laparoscopic cholecystectomy. We were unable to
      identify trials comparing one type of robot assistant versus another. Further
      randomised trials with low bias-risk and random errors are needed.

PMID- 19160290
TI  - Culture-specific programs for children and adults from minority groups who have
      asthma.
AB  - BACKGROUND: People with asthma who come from minority groups have poorer asthma
      outcomes and more asthma related visits to Emergency Departments (ED). Various
      programmes are used to educate and empower people with asthma and these have
      previously been shown to improve certain asthma outcomes. Models of care for
      chronic diseases in minority groups usually include a focus of the cultural
      context of the individual and not just the symptoms of the disease. Therefore,
      questions about whether culturally specific asthma education programmes for
      people from minority groups are effective at improving asthma outcomes, are
      feasible and are cost-effective need to be answered. OBJECTIVES: To determine
      whether culture-specific asthma programmes, in comparison to generic asthma
      education programmes or usual care, improve asthma related outcomes in children
      and adults with asthma who belong to minority groups. SEARCH STRATEGY: We
      searched the Cochrane Register of Controlled Trials (CENTRAL), the Cochrane
      Airways Group Specialised Register, MEDLINE, EMBASE, review articles and
      reference lists of relevant articles. The latest search was performed in May
      2008. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing the
      use of culture-specific asthma education programmes with generic asthma education
      programmes, or usual care, in adults or children from minority groups who suffer
      from asthma. DATA COLLECTION AND ANALYSIS: Two review authors independently
      selected, extracted and assessed the data for inclusion. We contacted authors for
      further information if required. MAIN RESULTS: Four studies were eligible for
      inclusion in the review. A total of 617 patients, aged from 5 to 59 years were
      included in the meta-analysis of data. Use of a culture-specific programme was
      superior to generic programmes or usual care, in improving asthma quality of life
      scores in adults, pooled WMD 0.25 (95% CI 0.09 to 0.41), asthma knowledge scores
      in children, WMD 3.30 (95% CI 1.07 to 5.53), and in a single study, reducing
      asthma exacerbation in children (risk ratio for hospitalisations 0.32, 95%CI
      0.15, 0.70). AUTHORS' CONCLUSIONS: Current limited data show that culture
      specific programmes for adults and children from minority groups with asthma, are
      more effective than generic programmes in improving most (quality of life, asthma
      knowledge, asthma exacerbations, asthma control) but not all asthma outcomes.
      This evidence is limited by the small number of included studies and the lack of
      reported outcomes. Further trials are required to answer this question
      conclusively.

PMID- 19160291
TI  - In vitro maturation in sub fertile women with polycystic ovarian syndrome
      undergoing assisted reproduction.
AB  - BACKGROUND: Polycystic ovarian syndrome (PCOS) occurs in 4% to 7% of all women of
      reproductive age and 20% of women presenting with sub-fertility. A significant
      proportion of these women will ultimately need assisted reproductive techniques
      (ART). In women with PCOS, the supra-physiological doses of gonadotrophins used
      for controlled ovarian hyperstimulation (COH) often result in an exaggerated
      ovarian response characterised by the development of a large cohort of follicles
      of uneven quality, retrieval of immature oocytes, and increased risk of ovarian
      hyperstimulation syndrome. A potentially useful intervention for women with PCOS
      related infertility involves earlier retrieval of immature oocytes followed by in
      vitro maturation (IVM). OBJECTIVES: To compare live birth rates per woman
      following in vitro maturation (IVM) with conventional in vitro fertilisation
      (IVF) or intracytoplasmic sperm injection (ICSI) for women with PCOS undergoing
      ART. SEARCH STRATEGY: We searched the Menstrual Disorders and Subfertility Group
      Specialised Register of controlled trials for any relevant trials from the title,
      abstract, or keyword sections. Following a search of electronic databases
      (MEDLINE in all languages) using Ovid software we also performed a manual search
      of the references of all retrieved articles, sought unpublished papers and
      abstracts submitted to international conferences, and contacted experts. In
      addition, we searched the National Institute of Clinical Excellence fertility
      assessment and treatment guidelines (NICE 2004) and handsearched reference lists
      of relevant systematic reviews and randomised trials. SELECTION CRITERIA: All
      randomised trials on the intention to perform IVM before IVF or ICSI and
      conventional IVF or ICSI for sub-fertile women with PCOS. DATA COLLECTION AND
      ANALYSIS: We identified no studies that met the inclusion criteria. MAIN RESULTS:
      There were no trials suitable for inclusion in the review. AUTHORS' CONCLUSIONS:
      There are no randomised controlled trials upon which to base any practice
      recommendations regarding IVM before IVF or ICSI for women with PCOS. There is an
      urgent need for randomised trials in this field.

PMID- 19160292
TI  - Interferon beta for primary progressive multiple sclerosis.
AB  - BACKGROUND: Therapeutic trials with ss-interferon in Multiple Sclerosis (MS) have
      mainly focused on remitting-relapsing multiple sclerosis (RRMS), demonstrating a
      reduction in relapse rate. However, there is not enough evidence about their
      efficacy in patients with primary progressive multiple sclerosis (PPMS).
      OBJECTIVES: Identify and summarize the evidence that ss-interferon is beneficial
      and safe in patients with PPMS. SEARCH STRATEGY: We searched (until April 2008)
      the Cochrane MS Group Trials Register; The Cochrane Central Register of
      Controlled Trials (CENTRAL) The Cochrane Library, (2008, Issue 3,); MEDLINE
      (PubMed) (January 1966 to April 2008), EMBASE (January 1974 to April 2008); NICE
      (January 1999 to April 2008); LILACS (January 1986 to April 2008); Screening of
      reference lists of all primary studies found; Contact and inquiry of drug
      manufactures and multiple sclerosis experts. SELECTION CRITERIA: Randomized
      double or single blind, placebo-controlled trials of recombinant ss-interferon in
      patients with PPMS including trials of MS which report separate outcomes in
      subgroups of patients with PPMS. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted and assessed trials' quality according to the criteria
      outlined in The Cochrane Handbook. MAIN RESULTS: Of 1280 potential studies
      evaluated, only two Randomized Control Trials (123 patients) were included. ss
      interferon treatment compared to placebo did not show differences regarding the
      proportion of patients with progression of the disease (RR 0.89, 95% CI 0.55
      to1.43), and it was associated with a greater frequency of treatment-related
      adverse events (RR 1.90, 95% CI 1.45-2.48). One of the trials evaluated the MRI
      secondary outcome pre-specified in the protocol. This trial showed that at two
      years the numbers of active lesions on brain MRI scan in ss-interferon arm were
      significantly lower than in placebo arm (weighted mean difference -1.3, 95% CI 
      2.15 to -0.45, P = 0.003); also, the number of participants with active lesions
      was significantly higher in placebo arm vs. ss-interferon arm at two years (RR
      0.43, 95% CI 0.22 to 0.86, P = 0.02). AUTHORS' CONCLUSIONS: Limited data on the
      effect of ss-interferon treatment on PPMS exists. Only two single-centre placebo
      controlled trials of interferon beta have been done. Based on this review, the
      included studies showed that ss-interferon treatment was not associated with
      reduced disability progression in PPMS patients. However, the trial population
      was too small to allow definitive conclusions on the efficacy of ss-interferon
      therapy in PPMS patients. Larger research studies need to be done in patients
      with PPMS in order to clarify whether ss-interferon is effective in this
      population.

PMID- 19160293
TI  - Treatment including anthracyclines versus treatment not including anthracyclines
      for childhood cancer.
AB  - BACKGROUND: One of the most important adverse effects of anthracyclines is
      cardiotoxicity. A well-informed decision on the use of anthracyclines in the
      treatment of different types of childhood cancer should be based on the available
      evidence on both antitumour efficacy and cardiotoxicity. OBJECTIVES: To compare
      antitumour efficacy of treatment including or not including anthracyclines in
      children with childhood cancer. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (The Cochrane Library 2006, issue 4), MEDLINE (1966
      to January 2007) and EMBASE (1980 to January 2007). In addition, we searched
      reference lists of relevant articles, conference proceedings and ongoing trials
      databases. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing
      treatment of any type of childhood cancer with and without anthracyclines and
      reporting outcomes concerning antitumour efficacy. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently performed the study selection, quality assessment and
      data-extraction. MAIN RESULTS: We identified RCTs for 5 types of tumour: acute
      lymphoblastic leukaemia (ALL) (n=3; 912 children), Wilms' tumour (n=1; 316
      children), rhabdomyosarcoma/undifferentiated sarcoma (n=1; 413 children), Ewing's
      sarcoma (n=1; 94 children), and non-Hodgkin lymphoma (n=1; 284 children). All
      studies had methodological limitations. For ALL no evidence of a significant
      difference in antitumour efficacy was identified in the meta-analyses, but in
      most individual studies there was a suggestion of better antitumour efficacy in
      patients treated with anthracyclines. For both Wilms' tumour and Ewing's sarcoma
      a significant difference in survival in favour of treatment with anthracyclines
      was identified. The hazard ratios for overall and event-free survival in Wilms'
      tumour were 1.85 (95% CI 1.09 to 3.15) and 2.21 (95% CI 1.44 to 3.40),
      respectively. For patients with Ewing's sarcoma only descriptive results were
      available (P = 0.02 for overall survival and P = 0.01 for event-free survival).
      For both rhabdomyosarcoma/undifferentiated sarcoma and non-Hodgkin lymphoma no
      difference in antitumour efficacy between the treatment groups was identified.
      Clinical cardiotoxicity was evaluated in 3 RCTs. No significant difference
      between both treatment groups was identified, but in all individual studies there
      was a suggestion of a lower rate of clinical cardiotoxicity in patients who did
      not receive anthracyclines. None of the studies evaluated asymptomatic cardiac
      dysfunction. For other childhood cancers no RCTs were identified. AUTHORS'
      CONCLUSIONS: At the moment no evidence from RCTs is available which underscores
      the use of anthracyclines in ALL. However, it should be noted that "no evidence
      of effect", as identified in this review, is not the same as "evidence of no
      effect". For Wilms' tumour, rhabdomyosarcoma/undifferentiated sarcoma, Ewing's
      sarcoma, and non-Hodgkin lymphoma only 1 RCT was available and therefore, no
      definitive conclusions can be made about the antitumour efficacy of treatment
      with or without anthracyclines in these tumours. For other childhood cancers no
      RCTs were identified and therefore, no conclusions can be made about the
      antitumour efficacy of treatment with or without anthracyclines in these tumours.
      More high quality research is needed.

PMID- 19160294
TI  - Metformin added to insulin therapy for type 1 diabetes mellitus in adolescents.
AB  - BACKGROUND: In adolescents with type 1 diabetes, insulin resistance likely plays
      a role in the deterioration of metabolic control. In type 1 diabetes, addition of
      metformin to insulin therapy, to improve insulin sensitivity, has been assessed
      in a few trials involving few patients or in uncontrolled studies of short
      duration. No systematic reviews are available up to date to summarize the
      evidence about metformin addition to insulin therapy in adolescents with type 1
      diabetes. OBJECTIVES: To assess the effects of metformin added to insulin therapy
      for type 1 diabetes mellitus in adolescents. SEARCH STRATEGY: We searched The
      Cochrane Library, MEDLINE and EMBASE. We also searched databases of ongoing
      trials, reference lists of relevant reviews, and we contacted experts, authors
      and manufacturers. SELECTION CRITERIA: Any randomised controlled trial (RCT) of
      at least three months duration of treatment comparing metformin added to insulin
      therapy versus insulin therapy alone in adolescents with type 1 diabetes was
      included. Cross-over and quasi-randomised controlled trials were excluded. DATA
      COLLECTION AND ANALYSIS: Two reviewers read all abstracts, assessed quality and
      extracted data independently. Authors were contacted for missing data. MAIN
      RESULTS: Only two trials (60 participants) investigating the effect of metformin
      added to insulin therapy for three months in adolescents with poorly controlled
      type 1 diabetes could be included. Meta-analysis was not possible due to the
      clinical and methodological heterogeneity of data. Both studies suggested that
      metformin treatment lowered glycosylated haemoglobin A1c (HbA1c) in adolescents
      with type 1 diabetes and poor metabolic control. Improvements in insulin
      sensitivity, body composition or serum lipids were not documented in either
      study, however, one study showed a decrease in insulin dosage by 10%. Adverse
      effects were mainly gastrointestinal in both studies and hypoglycaemia in one
      study. No data on health-related quality of life, all-cause mortality or
      morbidity are currently available. AUTHORS' CONCLUSIONS: There is some evidence
      suggesting improvement of metabolic control in poorly controlled adolescents with
      type 1 diabetes, on addition of metformin to insulin therapy. Stronger evidence
      is required from larger studies, carried out over longer time periods to document
      the long-term effects on metabolic control, health-related quality of life as
      well as morbidity and mortality in those patients.

PMID- 19160295
TI  - Interventions for the prevention and treatment of herpes simplex virus in
      patients being treated for cancer.
AB  - BACKGROUND: Treatment of cancer is increasingly effective, but associated with
      oral complications such as mucositis, fungal infections, bacterial infections and
      viral infections such as the herpes simplex virus (HSV). OBJECTIVES: To examine
      the effects of interventions for the prevention or treatment or both, of herpes
      simplex virus in patients receiving treatment for cancer. SEARCH STRATEGY: We
      searched the following databases: Cochrane Oral Health Group's Trials Register,
      CENTRAL, MEDLINE, EMBASE, CINAHL, CANCERLIT, SIGLE and LILACS. The reference list
      of all related review articles and articles considered to be potentially relevant
      were checked for further trials. Authors of identified trials and known
      specialists in the field were also contacted in an attempt to identify any
      additional published or unpublished trials. Date of most recent search: November
      2008. SELECTION CRITERIA: All randomised controlled trials comparing
      interventions for the prevention or treatment or both of HSV infection in people
      being treated for cancer. Outcomes were presence/absence of clinical/culture
      positive HSV infections (prevention), time to complete healing of lesions
      (treatment), duration of viral shedding, recurrence of lesions, relief of pain,
      amount of analgesia, duration of hospital stay, cost of oral care, patient
      quality of life and adverse effects. DATA COLLECTION AND ANALYSIS: Data were
      independently extracted, in duplicate, by two review authors. Authors were
      contacted for details of randomisation, blindness and sample demographics where
      necessary. Quality assessment was carried out on randomisation, blindness,
      withdrawals and selective reporting. The Cochrane Collaboration's statistical
      guidelines were followed and risk ratio (RR) values were calculated using random
      effects models. MAIN RESULTS: Seventeen trials satisfied the inclusion criteria.
      Four trials evaluated preventative interventions for HSV lesions, three trials
      for viral isolates, and eight trials evaluated both outcome measures. A single
      trial reported on the cost of prophylaxis for HSV. Two trials evaluating
      treatment reported on time to healing, duration of viral shedding and relief of
      pain. No trials reported on duration of hospital stay, amount of analgesia or
      patient quality of life.In placebo controlled trials, aciclovir was found to be
      effective for the prevention of HSV infections as measured by oral lesions or
      viral isolates (RR = 0.16, 95% confidence interval (CI) 0.08 to 0.31 nine trials;
      RR = 0.17, 95% CI 0.07 to 0.37 nine trials). There is no evidence that
      valaciclovir is more efficacious than aciclovir, or that higher doses of
      valaciclovir are more effective than lower doses. Placebo was found to be more
      effective than prostaglandin E for prevention of viral isolates (RR = 1.87, 95%
      CI 1.12 to 3.14 one trial).Aciclovir was also found to be effective for the
      treatment of HSV in terms of duration of viral shedding (median of 2.5 days
      versus 17.0 days, P = 0.0002; 2 days compared to more than 9, P = 0.0008), time
      to first decrease in pain (median 3 days compared to 16, P = 0.04), complete
      resolution of pain (9.9 days compared to 13.6 days, P = 0.01; median of 6 days
      compared to 16, P = 0.05), 50% healing (median of 6 days compared to 11, P =
      0.01) and total healing (median 13.9 days compared to 20.7 days, P = 0.08; median
      of 8 days compared to 21, P = 0.0). AUTHORS' CONCLUSIONS: There is evidence that
      aciclovir is efficacious in the prevention and treatment of herpes simplex virus
      infections. There is no evidence that valaciclovir is more efficacious than
      aciclovir, or that a high dose of valaciclovir is better than a low dose of
      valaciclovir. There is evidence that as a prophylaxis, placebo is more
      efficacious than prostaglandin E. However, in all included trials, risk of bias
      is unclear.

PMID- 19160296
TI  - Alkylating agents for Waldenstrom's macroglobulinaemia.
AB  - BACKGROUND: Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell
      lymphoproliferative disorder characterized by bone marrow infiltration and
      production of monoclonal immunoglobulin. Uncertainty remains if alkylating
      agents, such as chlorambucil, melphalan or cyclophosphamide, are an effective
      form of management. OBJECTIVES: To assess the effects and safety of the
      alkylating agents on Waldenstrom's macroglobulinaemia (WM). SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (Issue 1, 2008),
      MEDLINE (1966 to 2008), EMBASE (1980 to 2008), the Chinese Biomedical Base (1982
      to 2008) and reference lists of articles.We also handsearched relevant conference
      proceedings from 1990 to 2008. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) comparing alkylating agents given concomitantly with radiotherapy,
      splenectomy, plasmapheresis, stem-cell transplantation in patients with a
      confirmed diagnosis of WM. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trial quality and extracted data. We contacted study
      authors for additional information. We collected adverse effects information from
      the trials. MAIN RESULTS: One trial involving 92 participants with
      pretreated/relapsed WM compared the effect of fludarabine versus the combination
      of cyclophosphamide (the alkylating agent), doxorubicin and prednisone (CAP).
      Compared to CAP, the Hazard ratio (HR) for deaths of treatment with fludarabine
      was estimated to be 1.04, with a standard error of 0.30 (95% CI 0.58 to 1.48) and
      it indicated that the mean difference of median survival time was -4.00 months,
      and 16.00 months for response duration. The relative risks (RR) of response rate
      was 2.80 (95% CI 1.10 to 7.12). There were no statistically difference in overall
      survival rate and median survival months, while on the basis of response rate and
      response duration, fludarabine seemed to be superior to CAP for
      pretreated/relapsed patients with macroglobulinaemia. AUTHORS' CONCLUSIONS:
      Although alkylating agents have been used for decades they have never actually
      been tested in a proper randomised trial. This review demonstrated that there is
      currently no evidence to suggest that alkylating agents are effective in treating
      Waldenstrom's macroglobulinaemia.

PMID- 19160297
TI  - Interventions for preventing late postnatal mother-to-child transmission of HIV.
AB  - BACKGROUND: Worldwide, mother-to-child transmission (MTCT) of human
      immunodeficiency virus type 1 (HIV) represents the most common means by which
      children acquire HIV infection. Efficacious and effective interventions to
      prevent in utero and intrapartum transmission of HIV infection have been
      developed and implemented. However, a large proportion of MTCT of HIV occurs
      postnatally, through breast milk transmission. OBJECTIVES: The objectives of this
      systematic review were to collate and assess the evidence regarding interventions
      to decrease late postnatal MTCT of HIV, and to determine the efficacy of such
      interventions in decreasing late postnatal MTCT of HIV, increasing overall
      survival, and increasing HIV-free survival. SEARCH STRATEGY: Electronic searches
      were undertaken using PubMed, EMBASE and other databases for 1980-2008. Hand
      searches of reference lists of pertinent reviews and studies, as well as
      abstracts from relevant conferences, were also conducted. Experts in the field
      were contacted to locate any other studies. The search strategy was iterative.
      SELECTION CRITERIA: Randomized clinical trials assessing the efficacy of
      interventions to prevent MTCT of HIV through breast milk were included in the
      analysis. Other trials and intervention cohort studies with relevant data also
      were included, but only when randomization was not feasible due to the nature of
      the intervention (i.e., infant feeding modality). DATA COLLECTION AND ANALYSIS:
      Data regarding HIV infection status and vital status of infants born to HIV
      infected women, according to intervention, were extracted from the reports of the
      studies. MAIN RESULTS: Six randomized clinical trials and one intervention cohort
      study were included in this review. Two trials addressed the issue of shortening
      the duration of (or eliminating) exposure to breast milk. In a trial of
      breastfeeding versus formula feeding, formula feeding was efficacious in
      preventing MTCT of HIV (the cumulative probability of HIV infection at 24 months
      was 36.7% in the breastfeeding arm and 20.5% in the formula arm [p = 0.001]), but
      the mortality and malnutrition rates during the first two years of life were
      similar in the two groups. In a trial of early cessation of breastfeeding, HIV
      free survival was similar between those children who ceased breastfeeding around
      four months of age and those who continued breastfeeding. Another trial
      addressing vitamin supplementation found more cases of HIV infection among
      children of mothers in the vitamin A arm. Efficacy for other vitamin supplements
      was not shown. An intervention cohort study evaluated the risk of MTCT according
      to infant feeding modality, and found increased risks of MTCT among breastfed
      children who also received solids (hazard ratio = 10.87, p = 0.018) as well as
      higher 3-month mortality rates (hazard ratio = 2.06) among infants given non-
      breast milk feedings (instead of exclusive breastfeeding). Three trials evaluated
      antiretroviral prophylaxis to breastfeeding infants. One trial found that
      breastfeeding with zidovudine prophylaxis (transmission rate = 9.0%) was not as
      effective as formula feeding (transmission rate 5.6%) in preventing late
      postnatal HIV transmission (p = 0.04). Breastfeeding with zidovudine prophylaxis
      and formula feeding had comparable HIV-free survival rates at 18 months (p =
      0.60). Two trials of extended nevirapine prophylaxis demonstrated efficacy. In
      the first (data combined from trials conducted in three different countries), a
      six-week course of nevirapine resulted in a lower risk of HIV transmission by six
      weeks of age (p=0.009), but not at six months of age (p = 0.016). In the second,
      nevirapine administration until 14 weeks of age (5.2%) or nevirapine with
      zidovudine until 14 weeks of age (6.4%) resulted in significantly lower risks of
      MTCT of HIV by 9 months of age than a control regimen of peripartum prophylaxis
      (10.6%) (p < 0.001). HIV-free survival was significantly better through the age
      of 9 months in both extended prophylaxis groups, and through the age of 15 months
      in the extended nevirapine group. AUTHORS' CONCLUSIONS: Complete avoidance of
      breastfeeding is efficacious in preventing MTCT of HIV, but this intervention has
      significant associated morbidity (e.g., diarrheal morbidity if formula is
      prepared without clean water). If breastfeeding is initiated, two interventions
      1). exclusive breastfeeding during the first few months of life; and 2) chronic
      antiretroviral prophylaxis to the infant (nevirapine alone, or nevirapine with
      zidovudine) are efficacious in preventing transmission.

PMID- 19160298
TI  - Iron supplementation for reducing morbidity and mortality in children with HIV.
AB  - BACKGROUND: The most prevalent haematologic disturbance associated with HIV in
      children (apart from CD4 lymphocytopenia) is anaemia. Anaemia associated with HIV
      arises from multiple mechanisms, including the direct inhibitory effect of HIV on
      red cell precursors, other locally prevalent and/or opportunistic infections,
      micronutrient deficiency, anaemia of chronic disease, and as a consequence of
      medicines given for HIV and/or other concurrent illnesses. Iron deficiency is the
      most common cause of nutritional anaemia globally. There is significant
      geographical overlap of areas of the world where iron deficiency anaemia (IDA)
      and paediatric HIV are distributed. Given the high prevalence of IDA, it is
      likely that many HIV-infected children also are iron deficient. The contribution
      of iron deficiency to anaemia in HIV-infected children has been described but is
      incompletely understood. Currently, iron supplementation for anaemic infants and
      children is routinely practiced without any obvious effect in most developing
      countries, which bear most of the burden of global paediatric HIV
      infections.Because iron deficiency and IDA are common in HIV-infected children in
      high-prevalence areas and because there are concerns about possible deleterious
      effects of iron, this review aims to assess the evidence for iron supplementation
      for reducing morbidity and mortality in HIV-infected children. OBJECTIVES: To
      determine whether iron supplementation improves clinical, immunologic, and
      virologic outcomes in children infected with HIV SEARCH STRATEGY: We used the
      comprehensive search strategy developed specifically by the Cochrane HIV/AIDS
      Review Group to identify HIV/AIDS randomised controlled trials, and searched the
      following electronic databases: MEDLINE (searched November 2007); Embase
      (searched December 2007); and CENTRAL (December 2007). This search was
      supplemented with a search of AIDSearch (searched December 2007) and NLM Gateway
      (searched December 2007) to identify relevant conference abstracts, as well as a
      search of the reference lists of all eligible articles. The search was not
      limited by language or publication status. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) of iron supplementation in any form and dose in HIV
      infected children aged 12 years and younger. DATA COLLECTION AND ANALYSIS: We
      independently screened the results of the search to select potentially relevant
      studies and to retrieve the full articles. We independently applied the inclusion
      criteria to the potentially relevant studies. No studies were identified that
      fulfilled the selection criteria. MAIN RESULTS: No RCTs of iron supplementation
      in HIV-infected children were found. AUTHORS' CONCLUSIONS:  IMPLICATIONS FOR
      CLINICAL PRACTICE: The current clinical practice of iron supplementation in HIV
      infected children is based on weak evidence comprising observational studies and
      expert opinions. IMPLICATIONS FOR RESEARCH: High-quality RCTs of iron
      supplementation are urgently required, especially in areas with significant
      overlap of high prevalence of HIV, iron deficiency anaemia, and malaria. Policy
      makers should prioritise funding for these trials.

PMID- 19160299
TI  - Surgery for cataracts in people with age-related macular degeneration.
AB  - BACKGROUND: Cataract and age-related macular degeneration (AMD) are significant
      causes of decreased vision in the elderly that often occur simultaneously.
      Although cataract surgery is an effective treatment for cataract-induced visual
      loss, some clinicians suspect that such an intervention may increase the risk of
      progression of underlying AMD and thus have deleterious effects on vision.
      OBJECTIVES: The objective of this review was to evaluate the effectiveness and
      safety of cataract surgery in eyes with AMD. SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the
      Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library, Issue 4,
      2008), MEDLINE (January 1966 to November 2008), EMBASE (January 1980 to November
      2008) and Latin American and Caribbean Literature on Health Sciences (LILACS)
      (January 1982 to November 2008). There were no language or date restrictions in
      the search for trials. The electronic databases were last searched on 4 November
      2008. SELECTION CRITERIA: We planned to include randomized controlled trials
      (RCTs) and quasi-randomized trials of eyes affected by both cataract and AMD in
      which cataract surgery would be compared to no surgery. DATA COLLECTION AND
      ANALYSIS: Two authors independently evaluated the search results against the
      inclusion and exclusion criteria. Discrepancies were resolved by discussion. MAIN
      RESULTS: We found no RCTs, thus no analysis was conducted. Evidence was limited
      to non-randomized clinical trials and prospective cohort and case-control
      studies. AUTHORS' CONCLUSIONS: At this time, it is not possible to draw reliable
      conclusions from the available data to determine whether cataract surgery is
      beneficial or harmful in people with AMD. Physicians will have to make practice
      decisions based on best clinical judgement until controlled trials are conducted
      and their findings published.

PMID- 19160300
TI  - Conventional versus LigaSure hemorrhoidectomy for patients with symptomatic
      Hemorrhoids.
AB  - BACKGROUND: Hemorrhoidectomy is a frequently performed surgical procedure and
      associated with postprocedural pain. The use of the Ligasure could result in a
      decreased incidence of pain as coagulation with high frequency currency and
      active feedback control over the power output has minimal thermal spread and
      limited tissue charring. OBJECTIVES: To compare patient tolerance focussing on
      pain following Ligasure and conventional hemorrhoidectomy in patients with
      symptomatic hemorrhoids. SEARCH STRATEGY: A multi-database (MEDLINE, EMBASE,
      CENTRAL and CINAHL) systematic search was conducted. Key journals were
      handsearched. There was no restriction on language. SELECTION CRITERIA:
      Randomized controlled trials comparing hemorroidectomy using the Ligasure
      technique with conventional diathermy techniques for symptomatic hemorrhoids in
      adult patients were included. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted data, assessed trial quality and resolved discrepancies
      together with a third party. Odd Ratios were generated for dichotomous variables.
      Weight Mean Differences were used for analysing continuous variables. Only random
      effects models were used. Heterogeneity was explored by sensitvity analysis. MAIN
      RESULTS: Twelve studies with 1142 patients met the inclusion criteria. The pain
      score at the first day following surgery was significantly less in the Ligasure
      group (10 studies, 835 patients, WMD -2.07 CI -2.77 to -1.38). Most outcomes
      concerning analgesics used (7 studies) and pain scores up to 7 days (5 studies)
      favoured the Ligasure-technique. The benefit was diminished at day 14 (VAS pain
      score, 4 studies, 183 patients, WMD -0.12 CI -0.37 to 0.12). The conventional
      technique took significantly longer to complete (11 trials, 9.15 minutes, CI 3.21
      to 15.09). There was no relevant difference in postoperative complications,
      symptoms of recurrent bleeding or incontinence at final follow-up. Hospital stay
      was similar for both groups (6 reports, 525 patients, WMD -0.19 CI -0.63 to
      0.24). Patients treated with the Ligasure-technique returned to work
      significantly earlier (4 studies, 451 patients, 4.88 days, CI 2.18 to 7.59).
      Sensitivity analysis on high quality studies, fixed effects models, open or
      closed conventional techniques revealed no clinical relevant different results.
      AUTHORS' CONCLUSIONS: Since the usage of the Ligasure technique results in
      significantly less immediate postoperative pain after hemoroidectomy without any
      adverse effect on postoperative complications, convalescence and incontinence
      rate, this technique is superior in terms of patient tolerance. Although there
      was a tendency for equal efficacy, more evaluation of the long-term risk of
      recurrent hemorrhoidal disease is required.

PMID- 19160301
TI  - Interventions for treating painful sickle cell crisis during pregnancy.
AB  - BACKGROUND: Sickle cell disease is a group of genetic haemoglobin disorders. All
      over the world, about 300,000 children with these disorders are born each year.
      Acute sickle cell pain episodes are the most common cause of hospitalisation.
      Pregnancy in women with sickle cell disease is associated with an increased
      incidence of maternal and fetal morbidity and mortality. The painful crisis is a
      severe complication of this illness, and it requires several interventions:
      packed red cell transfusion, fluid replacement therapy, analgesic drugs, oxygen
      therapy and steroids; but the approach is not standardised. OBJECTIVES: To assess
      the effectiveness and safety of different regimens of packed red cell
      transfusion, oxygen therapy, fluid replacement therapy, analgesic drugs, and
      steroids for the treatment of painful sickle cell crisis during pregnancy. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (December 2007), the Cochrane Cystic Fibrosis and Genetic Disorders
      Group's Trials Register (October 2007), LILACS database (1982 to December 2007)
      and the following web sites: ClinicalTrials.gov (http://www.clinicaltrials.gov)
      (December 5, 2007); Current Controlled Trials (http://controlled-trials.com/)
      (December 5, 2007), and Sistema de Informacion Esencial en Terapeutica y Salud
      (http://www.icf.uab.es/informacion/Papyrus/sietes.asp) (December 1, 2007). We
      also handsearched the European Haematology Association conference (June 2007),
      the American Society of Hematology conference (December 2007) and reference lists
      of all retrieved articles. SELECTION CRITERIA: We intended to include randomised
      clinical trials. DATA COLLECTION AND ANALYSIS: We intended to summarise data by
      standard Cochrane Collaboration methodologies. MAIN RESULTS: We could not find
      any randomised clinical trials on interventions (packed red cell transfusion,
      oxygen therapy, fluid replacement therapy, analgesic drugs, and steroids) for the
      treatment of painful sickle cell crisis during pregnancy. AUTHORS' CONCLUSIONS:
      This review found no randomised clinical trials on the safety and efficacy of
      interventions for treating painful sickle cell crisis during pregnancy. The
      effects of interventions need to be tested in randomised clinical trials.

PMID- 19160302
TI  - Thoracic stent graft versus surgery for thoracic aneurysm.
AB  - BACKGROUND: Thoracic aortic aneurysm (TAA) is an uncommon disease with an
      incidence of 10.4 per 100,000 inhabitants. It occurs mainly in older individuals
      and is evenly distributed among both sexes. There are no signs or symptoms
      indicative of the presence of the disease. Progressive but unpredictable
      enlargement of the dilated aorta is the natural course of the disease and can
      lead to rupture. Open chest surgical repair using prosthetic graft interposition
      has been a conventional treatment for TAAs. Despite improvements in surgical
      procedures perioperative complications remain significant. The alternative option
      of thoracic endovascular aneurysm repair (TEVAR) is considered a less invasive
      and potentially safer technique, with lower morbidity and mortality compared with
      conventional treatment. Evidence is needed to support the use of TEVAR for these
      patients, rather than open surgery. OBJECTIVES: The aim of this review is to
      assess the efficacy of TEVAR versus conventional open surgery in patients with
      TAAs. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched
      their Trials Register (last searched 10 October 2008), the Cochrane Central
      Register of Controlled Trials database (CENTRAL) (last searched The Cochrane
      Library 2008, Issue 4). SELECTION CRITERIA: Randomised controlled trials in which
      patients with TAAs were randomly assigned to TEVAR or open surgical repair. DATA
      COLLECTION AND ANALYSIS: Two review authors independently identified and
      evaluated potential trials for eligibility. Excluded studies were further checked
      by another author. We did not perform any statistical analyses as no randomised
      controlled trials were identified. MAIN RESULTS: We did not find any published or
      unpublished randomised controlled trials comparing TEVAR with conventional open
      surgical repair for the treatment of thoracic aortic aneurysms. AUTHORS'
      CONCLUSIONS: Though stent grafting of the thoracic aorta is technically feasible
      and non-randomised studies suggest reduction of early outcomes such as
      paraplegia, mortality and hospital stay, high quality randomised controlled
      trials assessing all clinically relevant outcomes including open-conversion,
      aneurysm exclusion, endoleaks, and late mortality are needed.

PMID- 19160303
TI  - Antiviral therapy for recurrent liver graft infection with hepatitis C virus.
AB  - BACKGROUND: Antiviral therapy to treat recurrent hepatitis C infection after
      liver transplantation is controversial. OBJECTIVES: To compare the therapeutic
      efficacy and side effects of different antiviral regimens in patients with
      hepatitis C re-infected grafts after liver transplantation. SEARCH STRATEGY: We
      searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the
      Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library,
      MEDLINE, EMBASE, and Science Citation Index Expanded until September 2007.
      SELECTION CRITERIA: Only randomised clinical trials (irrespective of language,
      blinding, or publication status) comparing various antiviral therapies (alone or
      in combination) in the treatment of hepatitis C virus recurrence in liver
      transplantation were considered for the review. DATA COLLECTION AND ANALYSIS: Two
      authors collected the data independently. We calculated the relative risk (RR) or
      weighted mean difference (WMD) with 95% confidence intervals (CI) using the fixed
      effect and the random-effects models based on available case-analysis. MAIN
      RESULTS: A total of 389 liver transplant recipients with proven hepatitis C
      recurrence were randomised in eleven trials to various interventions and
      controls. The mean proportion of genotype I was 77.8% in the seven trials that
      reported the genotype. Only one or two trials were included under each
      comparison. All the trials were of high risk of bias. There was no difference in
      the mortality, graft rejection, or in re-transplantation between intervention and
      control in any of the comparisons that reported these outcomes. None of the
      trials reported liver decompensation or quality of life. Life-threatening adverse
      effects were not reported in either group in any of the comparisons. Up to 87.5%
      of patients required reduction in dose and up to 42.9% of patients required
      cessation of treatment in the various comparisons because of adverse effects or
      because of patient's choice to stop treatment. AUTHORS' CONCLUSIONS: 1.
      Considering the lack of clinical benefit and the frequent adverse effects, there
      is currently no evidence to recommend antiviral treatment for recurrent liver
      graft infection with HCV. 2. Further randomised clinical trials with adequate
      trial methodology and adequate duration of follow-up are necessary.

PMID- 19160304
TI  - Interventions for preventing critical illness polyneuropathy and critical illness
      myopathy.
AB  - BACKGROUND: Critical illness polyneuro-and/or myopathy (CIP/CIM) is an important
      and frequent complication in the intensive care unit (ICU), causing delayed
      weaning from mechanical ventilation. It may increase ICU stay and mortality.
      OBJECTIVES: To examine the ability of any intervention to prevent the occurrence
      of CIP/CIM. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group
      Trials Register (October 2007), MEDLINE (January 1950 to April 2008), EMBASE
      (January 1980 to October 2007), checked bibliographies and contacted trial
      authors and experts in the field. SELECTION CRITERIA: All randomised controlled
      trials (RCTs), examining the effect of any intervention on the incidence of
      CIP/CIM in adult medical or surgical ICU patients. The primary outcome measure
      was the incidence of CIP/CIM after at least seven days in ICU, based on
      electrophysiological or clinical examination. DATA COLLECTION AND ANALYSIS: Two
      authors independently extracted the data. MAIN RESULTS: Three out of nine
      identified trials, provided data on our primary outcome measure. Two trials
      examined the effects of intensive insulin therapy versus conventional insulin
      therapy. Eight hundred and twenty-five out of 2748 patients randomised, were
      included in the analysis. The incidence of CIP/CIM was significantly reduced with
      intensive insulin therapy in the population screened for CIP/CIM (relative risk
      (RR) 0.65, 95% confidence interval (CI) 0.55 to 0.78) and in the total population
      randomised (RR 0.60, 95% CI 0.49 to 0.74). Duration of mechanical ventilation,
      duration of ICU stay and 180-day mortality but not 30-day mortality, were
      significantly reduced with intensive insulin therapy, in both the total and the
      screened population. Intensive insulin therapy significantly increased
      hypoglycaemic events and recurrent hypoglycaemia. Death within 24 hours of the
      hypoglycaemic event was not different between groups. The third trial examined
      the effects of corticosteroids versus placebo in 180 patients with prolonged
      acute respiratory distress syndrome. No significant effect of corticosteroids on
      CIP/CIM was found (RR 1.09, 95% CI 0.53 to 2.26). No effect on 180-day mortality,
      new serious infections and glycaemia at day seven was found. A trend towards
      fewer episodes of pneumonia and reduction of new events of shock was shown.
      AUTHORS' CONCLUSIONS: Substantial evidence shows that intensive insulin therapy
      reduces the incidence of CIP/CIM, the duration of mechanical ventilation,
      duration of ICU stay and 180-day mortality. There was a significant associated
      increase in hypoglycaemia. Further research needs to identify the clinical impact
      of this and strategies need to be developed to reduce the risk of hypoglycaemia.
      Limited evidence shows no significant effect of corticosteroids on the incidence
      of CIP/CIM, or on any of the other secondary outcome measures, except for a
      significant reduction of new episodes of shock. Strict diagnostic criteria for
      the purpose of research should be defined. Other interventions should be
      investigated in randomised controlled trials.

PMID- 19160305
TI  - Oscillating devices for airway clearance in people with cystic fibrosis.
AB  - BACKGROUND: Chest physiotherapy is widely prescribed to assist the clearance of
      airway secretions in people with cystic fibrosis (CF). Oscillating devices
      generate intra- or extra-thoracic oscillations orally or external to the chest
      wall. Internally they create variable resistances within the airways, generating
      controlled oscillating positive pressure which mobilises mucus. Extra-thoracic
      oscillations are generated by forces outside the respiratory system, e.g. high
      frequency chest wall oscillation. OBJECTIVES: To determine the effectiveness and
      acceptability of oscillating devices compared to other forms of physiotherapy to
      improve respiratory function, mucus clearance and other outcomes in people with
      CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic
      Disorders Group Trials Register comprising references identified from
      comprehensive electronic database searches and hand searches of relevant journals
      and abstract books of conference proceedings. Most recent search of the Cystic
      Fibrosis Trials Register: November 2008. SELECTION CRITERIA: Randomised
      controlled studies and controlled clinical studies of oscillating devices
      compared with any other form of physiotherapy in people with CF. DATA COLLECTION
      AND ANALYSIS: Two authors independently applied the inclusion criteria to
      publications and assessed the quality of the included studies. MAIN RESULTS: Two
      hundred and sixty-five studies were identified; thirty studies (total of 708
      participants) met the inclusion criteria. Single treatment interventions (therapy
      technique used only once in the comparison) were excluded. Studies varied in
      duration from up to one week to one year in duration. Nineteen of the studies
      were cross-over in design. Data were not published in sufficient detail in most
      of these studies to perform meta-analysis.Forced expiratory volume in one second
      (FEV(1)) was the most frequently measured outcome. Results did not show
      significant difference in effect between oscillating devices and other methods of
      airway clearance on FEV(1) or other lung function parameters. Where there has
      been a small but significant change in secondary outcome variables such as sputum
      volume or weight this has not been wholly in favour of oscillating devices.
      Participant satisfaction was reported in eleven studies, but this was not
      specifically in favour of an oscillating device as some participants preferred
      breathing techniques or techniques used prior to the study interventions. The
      results for the remaining outcome measures were not examined or reported in
      sufficient detail to provide any high level evidence. AUTHORS' CONCLUSIONS: There
      was no clear evidence that oscillation was a more or less effective intervention
      overall than other forms of physiotherapy. More adequately-powered long-term
      randomised controlled trials are needed.

PMID- 19160306
TI  - Dance therapy for schizophrenia.
AB  - BACKGROUND: Dance therapy or dance movement therapy (DMT) is defined as 'the
      psychotherapeutic use of movement as a process which furthers the emotional,
      social, cognitive, and physical integration of the individual'. It may be of
      value for people with developmental, medical, social, physical or psychological
      impairments. Dance therapy can be practiced in mental health rehabilitation
      units, nursing homes, day care centres and incorporated into disease prevention
      and health promotion programs. OBJECTIVES: To evaluate the effects of dance
      therapy for people with schizophrenia or schizophrenia-like illnesses compared
      with standard care and other interventions. SEARCH STRATEGY: We searched the
      Cochrane Schizophrenia Group Trials Register (July 2007), inspected references of
      all identified studies (included and excluded), and contacted first authors for
      additional data. SELECTION CRITERIA: We included all randomised controlled trials
      (RCTs) comparing dance therapy and related approaches with standard care or other
      psychosocial interventions for people with schizophrenia. DATA COLLECTION AND
      ANALYSIS: We reliably selected, quality assessed and extracted data. We excluded
      data where more than 30% of participants were lost to follow-up. For continuous
      outcomes we calculated a weighted mean difference; for binary outcomes we
      calculated a fixed-effect risk ratio (RR) and their 95% confidence intervals
      (CI). MAIN RESULTS: We included one single blind study (total n=45) of reasonable
      quality. It compared dance therapy plus routine care with routine care alone.
      Most people tolerated the treatment package but about 40% were lost in each group
      by four months (RR 0.68 CI 0.31 to 1.51). PANSS average endpoint total scores
      were similar in each group (WMD -0.50 CI -11.8 to 10.8) as were the positive
      subscores (WMD 2.50 CI -0.67 to 5.67). At the end of treatment significantly more
      people in the dance therapy group had a greater than 20% reduction in PANSS
      negative symptom score (RR 0.62 CI 0.39 to 0.97), and overall average negative
      endpoint scores were lower (WMD -4.40 CI -8.15 to 0.65). There was no difference
      in satisfaction score (average CAT score, WMD 0.40 CI -0.78 to 1.58) and quality
      of life data were also equivocal (average MANSA score, WMD 0.00 CI -0.48 to
      0.48). AUTHORS' CONCLUSIONS: There is no evidence to support - or refute - the
      use of dance therapy in this group of people. This therapy remains unproven and
      those with schizophrenia, their carers, trialists and funders of research may
      wish to encourage future work to increase high quality evidence in this area.

PMID- 19160307
TI  - Techniques for liver parenchymal transection in liver resection.
AB  - BACKGROUND: Blood loss during elective liver resection is one of the main factors
      affecting the surgical outcome. Different parenchymal transection techniques have
      been suggested to decrease blood loss. OBJECTIVES: To assess the benefits and
      risks of the different techniques of parenchymal transection during liver
      resections. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group
      Controlled Trials Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index
      Expanded (March 2008). SELECTION CRITERIA: We considered for inclusion all
      randomised clinical trials comparing different methods of parenchymal dissection
      irrespective of the method of vascular occlusion or any other measures used for
      lowering blood loss. DATA COLLECTION AND ANALYSIS: Two authors identified the
      trials and extracted the data on the population characteristics, bias risk,
      mortality, morbidity, blood loss, transection speed, and hospital stay
      independently of each other. We calculated the odds ratio (OR), mean difference
      (MD), or standardised mean difference (SMD) with 95% confidence intervals based
      on 'interntion-to-treat analysis' or 'available case analysis' using RevMan 5.
      MAIN RESULTS: We included seven trials randomising 556 patients. The comparisons
      include CUSA (cavitron ultrasound surgical aspirator) versus clamp-crush (two
      trials); radiofrequency dissecting sealer (RFDS) versus clamp-crush (two trials);
      sharp dissection versus clamp-crush technique (one trial); and hydrojet versus
      CUSA (one trial). One trial compared CUSA, RFDS, hydrojet, and clamp-crush
      technique. The infective complications and transection blood loss were greater in
      the RFDS than clamp-crush. There was no difference in the blood transfusion
      requirements, intensive therapy unit (ITU) stay, or hospital stay in this
      comparison. There was no significant differences in the mortality, morbidity,
      markers of liver parenchymal injury or liver dysfunction, ITU, or hospital stay
      in the other comparisons. The blood transfusion requirements were lower in the
      clamp-crush technique than CUSA and hydrojet. There was no difference in the
      transfusion requirements of clamp-crush technique and sharp dissection. Clamp
      crush technique is quicker than CUSA, hydrojet, and RFDS. The transection speed
      of sharp dissection and clamp-crush technique was not compared. There was no
      clinically or statistically significant difference in the operating time between
      sharp dissection and clamp-crush techniques. Clamp-crush technique is two to six
      times cheaper than the other methods depending upon the number of surgeries
      performed each year. AUTHORS' CONCLUSIONS: Clamp-crush technique is advocated as
      the method of choice in liver parenchymal transection because it avoids special
      equipment, whereas the newer methods do not seem to offer any benefit in
      decreasing the morbidity or transfusion requirement.

PMID- 19160308
TI  - Psychosocial interventions for reducing fatigue during cancer treatment in
      adults.
AB  - BACKGROUND: Fatigue is a common symptom in cancer patients receiving active
      treatment. There are a limited number of reviews evaluating interventions for
      fatigue during active treatment, and they are restricted to patients with
      advanced cancer, or to patients during radiotherapy. To date there is no
      systematic review on psychosocial interventions for fatigue during cancer
      treatment. OBJECTIVES: To evaluate if psychosocial interventions are effective in
      reducing fatigue in cancer patients receiving active treatment for cancer, and
      which types of psychosocial interventions are the most effective. SEARCH
      STRATEGY: In September 2008 we searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library), PUBMED, MEDLINE, EMBASE,
      CINAHL and PsycINFO, and checked the reference lists. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) were included which evaluated psychosocial
      interventions in adult cancer patients during treatment, with fatigue as an
      outcome measure. DATA COLLECTION AND ANALYSIS: Three review authors independently
      extracted data from the selected studies, and assessed the methodological quality
      using several quality rating scales and additional criteria. MAIN RESULTS: Twenty
      seven studies met the inclusion criteria with a total of 3324 participants, and
      seven studies reported significant effects of the psychosocial intervention on
      fatigue. In three studies the effect was maintained at follow-up. The quality of
      the studies was generally moderate. Effect sizes varied between 0.17 to 1.07.The
      effectiveness of interventions specific for fatigue was significantly higher
      (80%) compared to interventions not specific for fatigue (14%). In five studies
      the interventions were specifically focused on fatigue, with four being
      effective. The five interventions were brief, consisting of three individual
      sessions, provided by (oncology) nurses. In general, during these interventions
      participants were educated about fatigue, were taught in self-care or coping
      techniques, and learned activity management.Of the remaining 22 studies only
      three were effective in reducing fatigue, and these interventions had a more
      general approach. These interventions were aimed at psychological distress, mood
      and physical symptoms, and varied strongly in duration and content. AUTHORS'
      CONCLUSIONS: There is limited evidence that psychosocial interventions during
      cancer treatment are effective in reducing fatigue. At present, psychosocial
      interventions specifically for fatigue are a promising type of intervention.
      However, there is no solid evidence for the effectiveness of interventions not
      specific for fatigue. Most aspects of the included studies were heterogeneous,
      and therefore it could not be established which other types of interventions, or
      elements were essential in reducing fatigue.

PMID- 19160309
TI  - High versus low dose of initial thyroid hormone replacement for congenital
      hypothyroidism.
AB  - BACKGROUND: Congenital hypothyroidism (CHT) affects approximately one in 3000 to
      4000 infants. CHT is one of the most common preventable causes of learning
      difficulties. Optimal management of CHT requires early diagnosis and prompt
      treatment to avoid abnormal neurodevelopmental outcome. One of the main issues in
      the management of CHT relates to the initial dose of levothyroxine to be used in
      order to achieve optimal results in terms of intellectual development. Currently,
      it remains unclear whether high dose thyroid hormone replacement is more
      effective than low dose in the treatment of CHT. Further research is required to
      determine an appropriate dose that improves mental and psychomotor developmental
      outcomes. OBJECTIVES: To determine the effects of high versus low dose of initial
      thyroid hormone replacement for congenital hypothyroidism. SEARCH STRATEGY:
      Randomised controlled trials were identified by searching The Cochrane Library,
      MEDLINE and EMBASE and reference lists of published papers. SELECTION CRITERIA:
      Randomised controlled clinical trials investigating the effects of high versus
      low dose of initial thyroid hormone replacement for congenital hypothyroidism
      were included. DATA COLLECTION AND ANALYSIS: Both authors independently selected
      trials, assessed risk of bias and extracted data. MAIN RESULTS: The initial
      search identified 1014 records which identified 13 publications for further
      examination. After screening the full text of the 13 selected papers, only one
      study evaluating 47 babies finally met the inclusion criteria. Using the same
      cohort at two different time periods, the study investigated the effects of high
      versus low dose thyroid hormone replacement in relation to (1) time taken to
      achieve euthyroid status and (2) neurodevelopmental outcome. The study reported
      that a high dose is more effective in rising serum thyroxine and free thyroxine
      concentrations to the target range and earlier normalisation of thyroid
      stimulating hormone compared to a lower dose. Similarly, full scale intelligence
      quotient was noted to be significantly higher in children who received the high
      dose compared to the lower dose. However, the verbal intelligence quotient and
      performance intelligence quotient were similar in both groups. Growth and adverse
      effects were not reported in the included trial. AUTHORS' CONCLUSIONS: There is
      currently only one randomised controlled trial evaluating the effects of high
      versus low dose of initial thyroid hormone replacement for CHT. There is
      inadequate evidence to suggest that a high dose is more beneficial compared to a
      low dose initial thyroid hormone replacement in the treatment of CHT.

PMID- 19160310
TI  - Decompressive surgery for treating nerve damage in leprosy.
AB  - BACKGROUND: Leprosy causes nerve damage which may result in nerve function
      impairment and disability. Decompressive surgery is used for treating nerve
      damage, although the effect is uncertain. OBJECTIVES: To assess the effects of
      decompressive surgery on nerve damage in leprosy. SEARCH STRATEGY: We searched
      the Cochrane Neuromuscular Disease Group Trials Register (November 2007), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4,
      2007), MEDLINE (from January 1950 to November 2007), EMBASE (from January 1980 to
      November 2007), AMED (from January 1985 to November 2007), CINAHL (from January
      1982 to November 2007) and LILACS (from January 1982 to November 2007) in
      November 2007. We checked reference lists of the studies identified, the Current
      Controlled Trials Register (www.controlled-trials.com), conference proceedings
      and contacted trial authors. SELECTION CRITERIA: Randomised and quasi-randomised
      controlled trials of decompressive surgery for nerve damage in leprosy. DATA
      COLLECTION AND ANALYSIS: The primary outcome was improvement in sensory and motor
      nerve function after one year. Secondary outcomes were improvement in nerve
      function after two years, change in nerve pain and tenderness, and adverse
      events. Two authors independently extracted data and assessed trial quality. We
      contacted trial authors for additional information. We collected adverse effects
      information from the trials and non-randomised studies. MAIN RESULTS: We included
      two randomised controlled trials involving 88 people. The trials examined the
      added benefit of surgery over prednisolone for treatment of nerve damage of less
      than six months duration. After two years follow-up there was no significant
      difference in nerve function improvement between people treated with surgery plus
      prednisolone or with prednisolone alone. Adverse effects of decompressive surgery
      were not adequately described. AUTHORS' CONCLUSIONS: Decompressive surgery is
      used for treating nerve damage in leprosy but evidence from randomised controlled
      trials does not show a significant added benefit of surgery over steroid
      treatment alone. Well-designed randomised controlled trials are needed to
      establish the effectiveness of the combination of surgery and medical treatment
      compared to medical treatment alone.

PMID- 19160311
TI  - Radioiodine therapy for differentiated thyroid carcinoma with thyroglobulin
      positive and radioactive iodine negative metastases.
AB  - BACKGROUND: Differentiated thyroid carcinoma with thyroglobulin positive and
      radioactive iodine negative metastases has been observed in follow-up studies.
      The management of this condition remains controversial. Most studies support
      blind radioactive iodine treatment while others negate this approach. OBJECTIVES:
      To assess the effects of radioiodine therapy for differentiated thyroid carcinoma
      with thyroglobulin positive and radioactive iodine negative metastases. SEARCH
      STRATEGY: Studies were obtained from computerised searches of MEDLINE, EMBASE,
      The Cochrane Library, China National Infrastructure (CNKI) and paper collections
      of conferences held in Chinese. SELECTION CRITERIA: Randomised controlled
      clinical trials and prospective controlled clinical trials. DATA COLLECTION AND
      ANALYSIS: Two authors independently extracted data and interviewed authors of all
      potentially relevant studies by electronic mail to verify randomisation
      procedures. One author entered data into a data extraction form and the second
      one verified the results of this procedure. MAIN RESULTS: Because of the absence
      of any suitable randomised or prospective controlled trial in this area, results
      currently cannot be presented. AUTHORS' CONCLUSIONS: The currently available
      evidence is insufficient to reliably assess the potential of radioiodine
      treatment for differentiated thyroid carcinoma with thyroglobulin positive and
      radioactive iodine negative metastases.

PMID- 19160312
TI  - Hematopoietic stem cell transplantation for children with sickle cell disease.
AB  - BACKGROUND: Sickle cell disease is a genetic disorder involving a defect in the
      red blood cells due to its sickled hemoglobin. The main therapeutic interventions
      include preventive and supportive measures. Hematopoietic stem cell
      transplantations are carried out with the aim of replacing the defective cells
      and their progenitors (hematopoietic (i.e. blood forming) stem cells) in order to
      correct the disorder. OBJECTIVES: To determine whether stem cell transplantation
      can improve survival and prevent symptoms and complications associated with
      sickle cell disease. To examine the risks of stem cell transplantation against
      the potential long-term gain for people with sickle cell disease. SEARCH
      STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group
      Group's Haemoglobinopathies Trials Register complied from electronic searches of
      the Cochrane Central Register of Controlled Trials (Clinical Trials) (updated
      each new issue of The Cochrane Library) and quarterly searches of
      MEDLINE.Unpublished work was identified by searching the abstract books of major
      conference proceedings and we conducted a search of the website:
      www.ClinicalTrials.gov.Date of the most recent search of the Group's
      Haemoglobinopathies Trials Register: September 2008. SELECTION CRITERIA:
      Randomized controlled and quasi-randomized studies that compared any method of
      stem cell transplantation with either each other or with any of the preventive or
      supportive interventions (e.g. periodic blood transfusion, use of hydroxyurea,
      antibiotics, pain relievers, supplemental oxygen) in children under 16 years of
      age irrespective of the type of sickle cell disease, gender and setting. DATA
      COLLECTION AND ANALYSIS: No relevant trials have been identified. MAIN RESULTS:
      Ten trials were identified by the initial search of which none were suitable for
      inclusion in this review. AUTHORS' CONCLUSIONS: Reports on the use of
      hematopoietic stem cell transplantation improving survival and preventing
      symptoms and complications associated with sickle cell disease are currently
      limited to observational and other less robust studies. No randomized controlled
      trial has assessed the benefit or risk of different types of hematopoietic stem
      cell transplantations in children. Thus, this systematic review identifies the
      need for a multicentre randomized controlled trial assessing the benefits and
      possible risks of different types of hematopoietic stem cell transplantations
      comparing sickle status and severity of disease in children.

PMID- 19160313
TI  - Amfetamine for attention deficit hyperactivity disorder in people with
      intellectual disabilities.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is increasingly
      recognised as occurring in people with intellectual disability (ID), although
      treatment of ADHD in this population has not been tested widely. Amfetamine has
      been used to treat ADHD in people with and without ID, although the evidence for
      its efficacy in people with ID is unclear. OBJECTIVES: To examine the
      effectiveness of amfetamine for the treatment of attention deficit hyperactivity
      disorder in people with intellectual disabilities. SEARCH STRATEGY: MEDLINE,
      PsycINFO, EMBASE, AMED, ISI Web of Science and WorldCat Dissertations were
      searched using an extensive list of synonyms for ADHD and ID. CENTRAL, Current
      Controlled Trials meta-register (mRCT), CenterWatch, NHS National Research
      Register, clinicaltrials.gov were searched in August 2007. Pharmaceutical
      companies and experts in the field were contacted. Reference lists of review
      articles were examined and citation searches were performed in ISI Web of
      Knowledge. SELECTION CRITERIA: All randomised controlled studies, both published
      and unpublished, in any language, in which children or adults with ADHD and ID
      were treated with amfetamine. DATA COLLECTION AND ANALYSIS: Data were extracted
      independently by two reviewers using a standardised extraction sheet. Risk of
      bias was assessed by two authors using a standardised framework. Meta-analyses
      were planned but were not performed due to a lack of suitable studies. MAIN
      RESULTS: Only one study was suitable for inclusion. This was a cross-over study
      in 15 children with ADHD, ID and Fragile X syndrome. Duration of treatment was
      only one week. No significant difference was reported between amfetamine and
      placebo for any of the ADHD measures, but significantly more side effects were
      reported while taking amfetamine, mainly mood lability and irritability. AUTHORS'
      CONCLUSIONS: There is very little evidence for the effectiveness of amfetamine
      for ADHD in people with ID . Prescribing in this population is based on
      extrapolation of research in people without ID. More research into effectiveness
      and tolerability is urgently needed.

PMID- 19160314
TI  - Beta-blockers for congestive heart failure in children.
AB  - BACKGROUND: Beta-blockers are an essential part of standard therapy in adult
      congestive heart failure and are therefore also expected to be beneficial in
      children. However, congestive heart failure in children differs strongly from
      that in adults in terms of characteristics and aetiology; also, an increased drug
      clearance has been reported. Paediatric needs have therefore to be specifically
      investigated. OBJECTIVES: To assess the effect of beta-adrenoceptor-blockers in
      children with congestive heart failure. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4
      2007), MEDLINE (1966 to January 2008), EMBASE (1980 to January 2008), and LILACS
      (1980 to January 2008). Bibliographies of identified studies were checked. No
      language restrictions were applied. SELECTION CRITERIA: Randomised, controlled
      clinical trials investigating the effect of beta-blocker therapy on paediatric
      congestive heart failure. DATA COLLECTION AND ANALYSIS: Two authors independently
      extracted and assessed data from the included trials. MAIN RESULTS: Three studies
      with an overall number of 203 participants were identified. Two small studies,
      with 20 and 22 children respectively, showed an improvement of congestive heart
      failure, while a larger study with 161 participants showed no evidence of benefit
      over placebo in the composite measure of heart failure outcomes which was the
      main outcome measure of the trial (56% improvement in both the placebo and the
      treatment group, p=0.74). However, study populations showed vast differences with
      regard to treatment (choice of beta-blocker, dosing, duration of treatment), age
      and age range of the participants and in particular with regard to condition
      (aetiology and severity of heart failure; homogeneity of condition in the study
      population). In addition methods and outcome measures differed strongly and were
      not standardised. The results can therefore not be compared against each other.
      AUTHORS' CONCLUSIONS: There are not enough data to recommend or discourage the
      use of beta-blockers in children with congestive heart failure. Further
      investigations in clearly defined populations with standardised methodology are
      required to establish guidelines for therapy. Pharmacokinetic investigations of
      beta-blockers in children are required to provide effective dosing in future
      trials.

PMID- 19160315
TI  - Cholecystectomy for gallbladder polyp.
AB  - BACKGROUND: The management of gallbladder polyps is controversial.
      Cholecystectomy has been recommended for gallbladder polyps larger than 10 mm
      because of the association with gallbladder cancer. Cholecystectomy has also been
      suggested for gallbladder polyps smaller than 10 mm in patients with biliary type
      of symptoms. OBJECTIVES: The aim of this review is to compare the benefits
      (relief of symptoms, decreased incidence of gallbladder cancer) and harms
      (surgical morbidity) of cholecystectomy in patients with gallbladder polyp(s).
      SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The
      Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until July
      2008 to identify the randomised trials. SELECTION CRITERIA: Only randomised
      clinical trials (irrespective of language, blinding, or publication status)
      comparing cholecystectomy and no cholecystectomy were considered for the review.
      DATA COLLECTION AND ANALYSIS: We planned to collect the data on the
      characteristics, methodological quality, mortality, number of patients in whom
      symptoms were improved or cured from the one identified trial. We planned to
      analyse the data using the fixed-effect and the random-effects models using
      RevMan Analysis. For each outcome we planned to calculate the risk ratio (RR)
      with 95% confidence intervals based on intention-to-treat analysis. MAIN RESULTS:
      We were unable to identify any randomised clinical trials comparing
      cholecystectomy versus no cholecystectomy in patients with a gallbladder polyp.
      AUTHORS' CONCLUSIONS: There are no randomised trials comparing cholecystectomy
      versus no cholecystectomy in patients with gallbladder polyps. Randomised
      clinical trials with low bias -risk are necessary to address the question of
      whether cholecystectomy is indicated in gallbladder polyps smaller than10 mm.

PMID- 19160316
TI  - Thrombophilia testing for prevention of recurrent venous thromboembolism.
AB  - BACKGROUND: Tests for thrombophilia are being performed on a large scale in
      people after venous thromboembolism (VTE) even though the benefits of testing are
      still subject to debate. The most important benefit would be a reduction in the
      risk of recurrent VTE due to the use of additional prophylactic measures.
      OBJECTIVES: The objective of this review was to assess the benefit of testing for
      thrombophilia after VTE in terms of risk reduction of recurrent VTE. SEARCH
      STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched their
      Trials Register (last searched 15 October 2008) and CENTRAL (last searched The
      Cochrane Library 2008, Issue 4). We searched MEDLINE, EMBASE, and reference
      lists. SELECTION CRITERIA: Randomized controlled trials (RCTs) and controlled
      clinical trials (CCTs) that compared the rate of recurrent VTE in participants
      with VTE who were tested for thrombophilia with the rate in participants with VTE
      who were not tested were eligible. DATA COLLECTION AND ANALYSIS: We planned to
      extract data from identified studies using data extraction forms. MAIN RESULTS:
      No studies were included because no RCTs or CCTs could be identified. AUTHORS'
      CONCLUSIONS: There are currently no randomized controlled trials or controlled
      clinical trials that have assessed the benefit(s) of testing for thrombophilia on
      the risk of recurrent VTE.

PMID- 19160317
TI  - Combination formoterol and inhaled steroid versus beta2-agonist as relief
      medication for chronic asthma in adults and children.
AB  - BACKGROUND: Formoterol has a fast onset of action and can therefore be used to
      relieve symptoms of asthma. A combination inhaler can deliver formoterol with
      different doses of inhaled corticosteroid; when used as a reliever both drugs
      will be delivered more frequently when asthma symptoms increase. This has the
      potential to treat both bronchoconstriction and inflammation in the early stages
      of exacerbations. OBJECTIVES: To assess the efficacy and safety of combined
      inhalers containing both formoterol and an inhaled corticosteroid when used for
      reliever therapy in adults and children with chronic asthma. SEARCH STRATEGY: We
      last searched the Cochrane Airways Group trials register in April 2008. SELECTION
      CRITERIA: Randomised trials in adults and children with chronic asthma, where a
      combination inhaler containing formoterol and inhaled corticosteroid is compared
      with fast-acting beta2-agonist alone for the relief of asthma symptoms. This
      should be the only planned difference between the trial arms. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted the characteristics and
      results of each study. Authors or manufacturers were asked to supply unpublished
      data in relation to primary outcomes. MAIN RESULTS: Three trials involving 5905
      participants were included. In patients with mild asthma who do not need
      maintenance treatment, no clinically important advantages of
      budesonide/formoterol as reliever were found in comparison to formoterol as
      reliever.Two studies enrolled patients with more severe asthma who were not
      controlled on high doses of inhaled corticosteroids (around 700 mcg/day in
      adults), and had suffered a clinically important asthma exacerbation in the past
      year. Hospitalisations related to asthma in the two studies comparing
      budesonide/formoterol for maintenance and relief with the same dose of
      budesonide/formoterol for maintenance with terbutaline for relief yielded an odds
      ratio of 0.68 (95% CI 0.40 to 1.16), which was not a statistically significant
      reduction. One adult study found a reduction in exacerbations requiring oral
      corticosteroids compared to terbutaline, odds ratio 0.56 (95% CI 0.42 to 0.74)
      and the study in children found less serious adverse events with
      budesonide/formoterol used for maintenance and relief. There was no significant
      difference in annual growth in children using budesonide/formoterol reliever in
      comparison to terbutaline. AUTHORS' CONCLUSIONS: In mild asthma it is not yet
      known whether patients who use a budesonide/formoterol inhaler for relief of
      asthma symptoms derive any clinically important benefits. In more severe asthma,
      one study that enrolled patients who were not controlled on quite high doses of
      inhaled corticosteroids, and had suffered an exacerbation in the previous year,
      demonstrated a reduction in the risk of exacerbations that require oral
      corticosteroids with budesonide/formoterol for maintenance and relief in
      comparison with budesonide/formoterol for maintenance and terbutaline or
      formoterol for relief. The incidence of serious adverse events in children was
      also less using budesonide/formoterol for maintenance and relief in one study,
      which similarly enrolled children who were not controlled on medium to high doses
      of inhaled corticosteroids, and compared to terbutaline relief with an
      explorative maintenance dose of budesonide/formoterol that is not approved for
      treatment.

PMID- 19160318
TI  - Cholecystectomy for suspected gallbladder dyskinesia.
AB  - BACKGROUND: The optimal treatment for patients with suspected biliary dyskinesia
      is controversial. Some studies found that cholecystectomy produced symptomatic
      improvement in patients with gallbladder dyskinesia (diagnosed by low gallbladder
      ejection fraction) while others found no significant benefit. Some studies have
      shown that gallbladder ejection fraction can discriminate patients who would
      benefit from cholecystectomy. Other studies have not confirmed this. OBJECTIVES:
      The aim of this review was to compare the benefits and harms of cholecystectomy
      for patients with suspected gallbladder dyskinesia. SEARCH STRATEGY: We searched
      The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE,
      EMBASE, and Science Citation Index Expanded until March 2008. SELECTION CRITERIA:
      We considered for inclusion all randomised clinical trials comparing
      cholecystectomy versus no cholecystectomy on patients with gallbladder
      dyskinesia. DATA COLLECTION AND ANALYSIS: We collected the data on the
      characteristics, methodological quality, mortality, number of patients in whom
      symptoms were improved or cured from the one identified trial. We planned to
      analyse the data using the fixed-effect and the random-effects models using
      RevMan Analysis. For each outcome we planned to calculate the risk ratio (RR)
      with 95% confidence intervals based on intention-to-treat analysis. MAIN RESULTS:
      We included one trial with 21 patients randomised: 11 to cholecystectomy and 10
      to control (no cholecystectomy). This trial was considered to be of high risk of
      bias as patients were not blinded and the procedure-related morbidity was not
      reported. There was no mortality in either group. All patients in the
      cholecystectomy group and only one patient in the control group had improvement
      in symptoms (P = 0.0001) after a mean follow-up period of 33.6 months. AUTHORS'
      CONCLUSIONS: The evidence for the benefits and harms of cholecystectomy in
      gallbladder dyskinesia from randomised clinical trials is based on a single small
      trial at risk of bias. Further randomised clinical trials with improved bias
      control are necessary to confirm or reject the promising results.

PMID- 19160319
TI  - First line chemotherapy in low risk gestational trophoblastic neoplasia.
AB  - BACKGROUND: Gestational trophoblastic neoplasia (GTN) is a rare but curable
      disease. The incidence in Europe and North America is nearly 1.5 per 1000 live
      births but much higher rates are reported from Africa and Asia. The majority of
      the patients respond to evacuation of the uterus plus or minus chemotherapy,
      however, occasional patients will die. Patients are categorised into low or high
      risk groups using a variety of scoring systems. A large number of regimens are
      used worldwide in the management of low risk GTN; there are reports of 14
      different regimens in the English literature. The choice of the regimen is
      usually dependent on geographic location, prior training and current experience
      with the specific regimen. Regimens have significant differences in the route of
      administration, hospitalisation and side effects and so have a bearing on
      healthcare cost. Patients are therefore exposed to different regimens with the
      potential for different response rates and different side effect profiles.
      OBJECTIVES: To determine the efficacy and safety of first line chemotherapy in
      the treatment of low risk GTN. SEARCH STRATEGY: We electronically searched
      Cochrane Gynaecological Cancer Group Specialized Register, Cochrane Central
      Register of Controlled Trials (CENTRAL, Issue 3 2008), MEDLINE and EMBASE in
      September 2008. We performed additional searching of online trial registers and
      conference proceedings. We cross examined article references to identify relevant
      papers not detected by the electronic search. SELECTION CRITERIA: The review
      included randomised controlled trials (RCTs) , quasi-RCTs and non-RCTs (cohort
      and case control studies (CCS)) for the treatment of low risk GTN. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed studies for
      inclusion in the review using a data extraction form. Meta-analysis was performed
      by pooling the relative risk (RR) of individual trials. MAIN RESULTS: Eight
      studies met the review entry criteria (n = 769). There were four RCTs and four
      CCS. Six different treatment regimens were identified; weekly methotrexate, 5-day
      methotrexate, 8-day methotrexate-folinic acid, "pulsed" dactinomycin, 5-day
      dactinomycin and the combination of methotrexate and dactinomycin. "Pulsed"
      dactinomycin was superior to weekly methotrexate in achieving primary cure
      without significantly increasing toxicity (three studies, RR 3.00, 95% CI 1.10 to
      8.17, n = 392) . Eight-day methotrexate-folinic acid did not show significant
      advantage over 5-day methotrexate both in reducing toxicity or primary cure rate
      (two studies, RR 1.07, 95% CI 0.91 to 1.25, n = 169). The combination of
      methotrexate-dactinomycin resulted in significantly increased toxicity without
      significantly improving primary cure rate. AUTHORS' CONCLUSIONS: Based on the
      available evidence from the included RCTs, the authors conclude that "pulsed"
      dactinomycin is superior to weekly parenteral methotrexate at the reported
      dosages. However, the authors believe that rigorously designed, multicentred,
      randomised double-blind trials are required to evaluate other combinations of
      chemotherapy regimens, most importantly "pulsed" dactinomycin with the widely
      used 8-day methotrexate-folinic acid.

PMID- 19160320
TI  - Prophylactic antibiotics or G-CSF for the prevention of infections and
      improvement of survival in cancer patients undergoing chemotherapy.
AB  - BACKGROUND: Febrile neutropenia (FN) and other infectious complications are some
      of the most serious treatment-related toxicities of chemotherapy for cancer, with
      a mortality rate of 2% to 21%. The two main types of prophylactic regimens are
      granulocyte (G-CSF) or granulocyte-macrophage colony stimulating factors (GM
      CSF); and antibiotics, frequently quinolones or cotrimoxazole. Important current
      guidelines recommend the use of colony stimulating factors when the risk of
      febrile neutropenia is above 20% but they do not mention the use of antibiotics.
      However, both regimens have been shown to reduce the incidence of infections.
      Since no systematic review has compared the two regimens, a systematic review was
      undertaken. OBJECTIVES: To compare the effectiveness of G-CSF or GM-CSF with
      antibiotics in cancer patients receiving myeloablative chemotherapy with respect
      to preventing fever, febrile neutropenia, infection, infection-related mortality,
      early mortality and improving quality of life. SEARCH STRATEGY: We searched The
      Cochrane Library, MEDLINE, EMBASE, databases of ongoing trials, and conference
      proceedings of the American Society of Clinical Oncology and the American Society
      of Hematology (1980 to 2007). We planned to include both full-text and abstract
      publications. SELECTION CRITERIA: Randomised controlled trials comparing
      prophylaxis with G-CSF or GM-CSF versus antibiotics in cancer patients of all
      ages receiving chemotherapy or bone marrow or stem cell transplantation were
      included for review. Both study arms had to receive identical chemotherapy
      regimes and other supportive care. DATA COLLECTION AND ANALYSIS: Trial
      eligibility and quality assessment, data extraction and analysis were done in
      duplicate. Authors were contacted to obtain missing data. MAIN RESULTS: We
      included two eligible randomised controlled trials with 195 patients. Due to
      differences in the outcomes reported, the trials could not be pooled for meta
      analysis. Both trials showed non-significant results favouring antibiotics for
      the prevention of fever or hospitalisation for febrile neutropenia. AUTHORS'
      CONCLUSIONS: There is no evidence for or against antibiotics compared to G(M)
      CSFs for the prevention of infections in cancer patients.

PMID- 19160321
TI  - Regimens of fetal surveillance for impaired fetal growth.
AB  - BACKGROUND: Policies and protocols for fetal surveillance in the pregnancy where
      impaired fetal growth is suspected vary widely, with numerous combinations of
      different surveillance methods. OBJECTIVES: To assess the effects of antenatal
      fetal surveillance regimens on important perinatal and maternal outcomes. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (April 2008). SELECTION CRITERIA: Randomised and quasi-randomised trials
      comparing the effects of described antenatal fetal surveillance regimens. DATA
      COLLECTION AND ANALYSIS: R Grivell and L Wong independently assessed trial
      eligibility and quality and extracted data. MAIN RESULTS: One trial of 167 women
      and their babies was included. This trial was a pilot study recruiting alongside
      another study, therefore a separate sample size was not calculated. The trial
      compared a twice-weekly surveillance regimen (biophysical profile, nonstress
      tests, umbilical artery and middle cerebral artery Doppler and uterine artery
      Doppler) with the same regimen applied fortnightly (both groups had growth
      assessed fortnightly). There were insufficient data to assess this review's
      primary infant outcome of composite perinatal mortality and serious morbidity
      (although there were no perinatal deaths) and no difference was seen in the
      primary maternal outcome of emergency caesarean section for fetal distress. In
      keeping with the more frequent monitoring, mean gestational age at birth was four
      days less for the twice-weekly surveillance group compared with the fortnightly
      surveillance group. Women in the twice-weekly surveillance group were 25% more
      likely to have induction of labour than those in the fortnightly surveillance
      group. The risk ratio was 1.25 (95% confidence interval 1.04 to 1.50). AUTHORS'
      CONCLUSIONS: There is limited evidence from randomised controlled trials to
      inform best practice for fetal surveillance. regimens when caring for women with
      pregnancies affected by impaired fetal growth. More studies are needed to
      evaluate the effects of currently used fetal surveillance regimens in impaired
      fetal growth.

PMID- 19160322
TI  - Palliative cytoreductive surgery versus other palliative treatments in patients
      with unresectable liver metastases from gastro-entero-pancreatic neuroendocrine
      tumours.
AB  - BACKGROUND: Neuroendocrine tumours are tumours of cells which possess secretory
      granules and originate from the neuroectoderm. While liver resection is generally
      advocated in patients with resectable liver alone metastases, the management of
      patients with liver metastases, which cannot be completely resected, is
      controversial. OBJECTIVES: To determine if cytoreductive surgery is better than
      other palliative treatments in patients with liver metastases from gastro-entero
      pancreatic neuroendocrine tumours, which cannot be completely resected. SEARCH
      STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The
      Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and LILACS
      until July 2008 for identifying the randomised trials. SELECTION CRITERIA: Only
      randomised clinical trials (irrespective of language, blinding, or publication
      status) comparing liver resection (alone or in combination with radiofrequency
      ablation or cryoablation) versus other palliative treatments (chemotherapy or
      hormone-therapy or immunotherapy) or no treatment in patients with liver
      metastases from neuroendocrine tumours, which cannot be completely resected, were
      considered for the review. DATA COLLECTION AND ANALYSIS: Two authors
      independently identified trials for inclusion. MAIN RESULTS: We were unable to
      identify any randomised clinical trial suitable for inclusion in this review.
      AUTHORS' CONCLUSIONS: The literature provides no evidence from randomised
      clinical trials in order to assess the role of cytoreductive surgery in non
      resectable liver metastases from gastro-entero-pancreatic neuroendocrine tumours.
      High-quality randomised clinical trials may become feasible to perform if their
      conduct and study design is thoroughly considered in all their practical and
      methodological aspects. Pilot randomised clinical trials, which can guide the
      study design of definitive randomised clinical trials, are necessary.

PMID- 19160323
TI  - The effect of social franchising on access to and quality of health services in
      low- and middle-income countries.
AB  - BACKGROUND: Social franchising has developed as a possible means of improving
      provision of health services through engaging the non-state sector in low- and
      middle-income countries. OBJECTIVES: To examine the evidence that social
      franchising has on access to and quality of health services in low- and middle
      income countries. SEARCH STRATEGY: We searched the Cochrane Effective Practice
      and Organisation of Care (EPOC) Group Specialised Register (up to October 2007),
      Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue
      3), MEDLINE, Ovid (1950 to September Week 3 2007), EMBASE, Ovid (1980 to 2007
      Week 38), CINAHL, Ovid (1982 to September Week 3 2007), EconLit, WebSPIRS (1969
      to Sept 2007), LILACS, Science Citation Index Expanded and Social Sciences
      Citation Index (1975 to March 2008), Sociological Abstracts, CSA Illumnia (1952
      September 2007), WHOLIS (1948 November 2007). SELECTION CRITERIA: Randomized
      controlled trials, non-randomized controlled trials, controlled before and after
      studies and interrupted time series comparing social franchising models with
      other models of health service delivery, other social franchising models or
      absence of health services. DATA COLLECTION AND ANALYSIS: Two review authors
      independently applied the criteria for inclusion and exclusion of studies to scan
      titles and abstracts. The same two review authors independently screened full
      reports of selected citations . At each stage, results were compared and
      discrepancies settled through discussion. MAIN RESULTS: No studies were found
      which were eligible for inclusion in this review. AUTHORS' CONCLUSIONS: There is
      a need to develop rigorous studies to evaluate the effects of social franchising
      on access to and quality of health services in low- and middle-income countries.
      Such studies should be informed by the wider literature to identify models of
      social franchising that have a sound theoretical basis and empirical research
      addressing their reach, acceptability, feasibility, maintenance and
      measurability.

PMID- 19160324
TI  - Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in
      neonates.
AB  - BACKGROUND: Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant
      neonatal mortality and morbidity in spite of appropriate antibiotic therapy.
      Enhancing host defence and modulating inflammation by using lactoferrin as an
      adjunct to antibiotics in the treatment of sepsis and/or NEC may improve clinical
      outcomes. OBJECTIVES: The primary objective is to assess safety and efficacy of
      oral lactoferrin as an adjunct to antibiotics in the treatment of neonates with
      suspected or confirmed sepsis and/or NEC. SEARCH STRATEGY: Relevant trials in any
      language were searched in June 2008 in the Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (1966 - June 2008),
      PREMEDLINE, EMBASE (1980 - June 2008), CINAHL (1982 - June 2008), web sites:
      www.clinicaltrials.gov and www.controlled-trials.com, abstracts from the annual
      meeting of Pediatric Academic Societies (1990- June 2008), by contacting authors
      who have published in this field, from the reference lists of identified clinical
      trials and in the reviewer's personal files. SELECTION CRITERIA: Randomized or
      quasi-randomized controlled trials evaluating oral lactoferrin (at any dose or
      duration) used as an adjunct to antibiotic therapy compared with antibiotic
      therapy alone (with or without placebo) or other adjuncts to antibiotic therapy
      to treat neonates at any gestational age up to 44 weeks postmenstrual age with
      confirmed or suspected sepsis or necrotizing enterocolitis (Bell's Stage II or
      III). DATA COLLECTION AND ANALYSIS: We used the standardized methods of the
      Cochrane Neonatal Review Group (CNRG) for conducting a systematic review and for
      assessing the methodological quality of the studies
      (http://neonatal.cochrane.org/en/index.html). The titles and the abstracts of
      studies identified by the search strategy were independently assessed by the two
      review authors and full text version was obtained for assessment if necessary.
      Forms were designed for trial inclusion/exclusion and data extraction. MAIN
      RESULTS: Our search strategy did not identify any eligible trials or potentially
      eligible ongoing neonatal trials. One trial was excluded and three ongoing or
      soon to be started adult trials using lactoferrin for the treatment of infections
      were identified. AUTHORS' CONCLUSIONS:  IMPLICATIONS FOR PRACTICE: Currently
      there is no evidence to recommend or refute the use of lactoferrin for the
      treatment of neonatal sepsis or necrotizing enterocolitis as an adjunct to
      antibiotic therapy. IMPLICATIONS FOR RESEARCH: The safety and efficacy of
      different preparations and doses of lactoferrin needs to be established in
      neonates. Well designed adequately powered randomized multicenter trials are
      needed to address the efficacy and safety of lactoferrin in the treatment of
      neonatal sepsis and necrotizing enterocolitis. These trials should evaluate long
      term neurodevelopmental and pulmonary outcomes in addition to short-term outcomes
      (e.g. mortality).

PMID- 19160325
TI  - Pre and peri-operative erythropoietin for reducing allogeneic blood transfusions
      in colorectal cancer surgery.
AB  - BACKGROUND: Patients with colorectal cancer are frequently anaemic and many
      receive allogeneic red blood cell transfusions peri and post-operatively.
      Transfusions are accompanied by complications and may increase the rate of
      recurrence in patients who have a colorectal resection. Recombinant
      erythropoietin was first used in dialysis patients and more recently in
      orthopedic surgery to facilitate autologous transfusions. Erythropoietin levels
      are thought to be lower in cancer patients and erythropoietin is widely used in
      chemotherapy to treat anaemia and improve quality of life. There may be adverse
      events associated with its use. Several studies have investigated erythropoietin
      in colorectal cancer surgery. OBJECTIVES: The primary objective of this
      systematic review was to evaluate the efficacy of erythropoietin pre and peri
      operatively, in reducing allogeneic blood transfusions in patients undergoing
      colorectal cancer surgery. Secondary objectives were to determine whether pre and
      peri-operative erythropoietin improves hematologic parameters (hemoglobin,
      hematocrit and reticulocyte count), quality of life, recurrence rate, and
      survival, without increasing the occurrence of thrombotic events and the peri
      operative mortality. SEARCH STRATEGY: A literature search was performed using
      MEDLINE, EMBASE, abstracts from the annual meetings of the American Society of
      Clinical Oncology and the American Society of Colon and Rectal Surgeons until May
      2008. SELECTION CRITERIA: Randomized controlled trials of erythropoietin versus
      placebo or no treatment/standard of care were eligible for inclusion. The study
      must have reported one of the primary or secondary outcomes and included anaemic
      patients undergoing surgery for colorectal cancer. DATA COLLECTION AND ANALYSIS:
      The methodological quality of the trials was assessed using the information
      provided. Data were extracted and effect sizes were estimated and reported as
      relative risks(RR) and mean differences (MD) as appropriate. MAIN RESULTS: Four
      eligible studies were identified of ten retrieved in full. There were no
      statistically significant differences in the proportion of patients transfused
      between the erythropoietin group and control group. One of the studies showed a
      small difference in the median number of units transfused per patient favouring
      treatment. Reporting of hematologic parameters was varied however, there is no
      evidence for clinically significant changes. There were no significant
      differences in post-operative mortality or thrombotic events between groups. No
      included study evaluated recurrences, survival, or quality of life. Studies were
      of fair methodologic quality and the overall sample size was small therefore
      results should be interpreted with caution. AUTHORS' CONCLUSIONS: There is no
      sufficient evidence to date to recommend pre and peri-operative erythropoietin
      use in colorectal cancer surgery.

PMID- 19160326
TI  - Resorbable versus titanium plates for facial fractures.
AB  - BACKGROUND: Rigid internal fixation of the jaw bones is a routine procedure for
      the management of facial fractures. Titanium plates and screws are routinely used
      for this purpose. The limitations of this system has led to the development of
      plates manufactured from bioresorbable materials which, in some cases, omits the
      necessity for the second surgery. However, concerns remain about the stability of
      fixation and the length of time required for their degradation and the
      possibility of foreign body reactions. OBJECTIVES: To compare the effectiveness
      of bioresorbable fixation systems with titanium systems for the management of
      facial fractures. SEARCH STRATEGY: We searched the following databases: The
      Cochrane Oral Health Group's Trials Register (to 20th August 2008), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue
      3), MEDLINE (1950 to 20th August 2008), EMBASE (from 1980 to 20th August 2008),
      http://www.clinicaltrials.gov/ and http://www.controlled-trials.com (to 20th
      August 2008). SELECTION CRITERIA: Randomised controlled trials comparing
      resorbable versus titanium fixation systems used for facial fractures. DATA
      COLLECTION AND ANALYSIS: Retrieved studies were independently screened by two
      review authors. Results were to be expressed as random-effects models using mean
      differences for continuous outcomes and risk ratios for dichotomous outcomes with
      95% confidence intervals. Heterogeneity was to be investigated including both
      clinical and methodological factors. MAIN RESULTS: The search strategy retrieved
      53 potentially eligible studies. None of the retrieved studies met our inclusion
      criteria and all were excluded from this review. One study is awaiting
      classification as we failed to obtain the full text copy. Three ongoing trials
      were retrieved, two of which were stopped before recruiting the planned number of
      participants. In one study, the excess complications in the resorbable arm was
      declared as the reason for stopping the trial. AUTHORS' CONCLUSIONS: This review
      illustrates that there are no published randomised controlled clinical trials
      relevant to this review question. There is currently insufficient evidence for
      the effectiveness of resorbable fixation systems compared with conventional
      titanium systems for facial fractures. The findings of this review, based on the
      results of the aborted trials, do not suggest that resorbable plates are as
      effective as titanium plates. In future, the results of ongoing clinical trials
      may provide high level reliable evidence for assisting clinicians and patients
      for decision making. Trialists should design their studies accurately and
      comprehensively to meet the aims and objectives defined for the study.

PMID- 19160327
TI  - Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis is an inherited condition resulting in thickened,
      sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary
      infection and inflammation, is the most common cause of mortality. Muco-active
      therapies (e.g. dornase alfa and nebulized hypertonic saline) may decrease sputum
      viscosity, increase airway clearance of sputum, reduce infection and inflammation
      and improve lung function. Thiol derivatives, either oral or nebulized, have
      shown benefit in other respiratory diseases. Their mode of action is likely to
      differ according to the route of administration. There are several thiol
      derivatives, and it is unclear which of these may be beneficial in cystic
      fibrosis. OBJECTIVES: To evaluate the efficacy and safety of nebulized and oral
      thiol derivatives in people with cystic fibrosis. SEARCH STRATEGY: We searched
      the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register,
      comprising references identified from comprehensive electronic database searches,
      hand searches of relevant journals, abstract books and conference
      proceedings.Most recent search: November 2008. SELECTION CRITERIA: Randomized and
      quasi-randomized controlled trials comparing nebulized or oral thiol derivatives
      to placebo or another thiol derivative in people with cystic fibrosis. DATA
      COLLECTION AND ANALYSIS: The authors independently assessed trials for inclusion,
      analysed methodological quality and extracted data. MAIN RESULTS: Searches
      identified 18 trials; eight (seven older than 10 years) (234 participants) are
      included. Three trials of nebulized thiol derivatives were identified (one
      compared 20% n-acetylcysteine to 2% n-acetylcysteine; another compared sodium-2
      mercaptoethane sulphonate to 7% hypertonic saline; and another compared
      glutathione to 4% hypertonic saline). Although generally well-tolerated with no
      significant adverse effects, there was no evidence of significant clinical
      benefit in our primary outcomes in participants receiving these treatments.Five
      studies of oral thiol derivatives were identified. Three studies compared n
      acetylcysteine to placebo; one compared n-acetylcysteine, ambroxol and placebo;
      and one compared carbocysteine to ambroxol. Oral thiol derivatives were generally
      well-tolerated with no significant adverse effects, however there was no evidence
      of significant clinical benefit in our primary outcomes in participants receiving
      these treatments. AUTHORS' CONCLUSIONS: We found no evidence to recommend the use
      of either nebulized or oral thiol derivatives in people with cystic fibrosis.
      There are very few good quality trials investigating the effect of these
      medications in cystic fibrosis, and further research is required to investigate
      the potential role of these medications in improving the outcomes of people with
      cystic fibrosis.

PMID- 19160328
TI  - Donepezil for dementia in people with Down syndrome.
AB  - BACKGROUND: Alzheimer's dementia (AD) is the most common form of dementia in
      people with Down Syndrome [DS]. Acetylcholine is a chemical found in the brain
      that has an important role in memory, attention, reason and language. Donepezil a
      reversible inhibitor of acetylcholinesterase, which is thought to maintain levels
      of acetylcholine, and is reported to have some benefits for people with AD in the
      general population. It is important to note that people with DS tend to present
      with AD at a much younger age than the normal population as well as having subtle
      differences in physiology (e.g. metabolism and heart rate) and may therefore have
      different requirements from the general population. OBJECTIVES: To determine the
      effectiveness and safety of donepezil for people with DS who develop AD. SEARCH
      STRATEGY: CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the
      NRR were searched up to October 2008. We contacted the manufacturers of donepezil
      as well as experts in the field, to ask about reports of unpublished or ongoing
      trials. SELECTION CRITERIA: Randomised controlled trials of participants with DS
      and AD in which treatment with donepezil was administered compared with a placebo
      group. DATA COLLECTION AND ANALYSIS: Data were extracted from the published
      reports of the one relevant study identified. MAIN RESULTS: The one study
      included in this review is a small (n=30) randomised controlled trial lasting 24
      weeks. It was followed-up by an open label study with a crossover design.No
      significant differences were found on any four validated outcomes including
      global functioning and three measures of cognitive abilities and behavioural
      problems. 6 out of 16 carers (37%) of participants on donepezil and 2 out of 15
      (13%) on placebo reported improvement. No data were available for day to day
      skills, institutionalisation, reduction in carers' stress or economic outcomes.
      Half the intervention group and 20% of the placebo group reported adverse events;
      two participants left because of adverse events. AUTHORS' CONCLUSIONS: To date
      there is only one small randomised controlled study on the effect of donepezil.
      This shows, at best, a modest, non statistically significant trend in favour of
      people with Down syndrome and Alzheimer's dementia who are able to tolerate
      donepezil (this drug is currently only dispensed in relatively large doses and is
      contraindicated for those with cardiac and respiratory problems).This study does
      not provide good evidence on which to base practice. Findings in an open-label
      follow up to this study suggest possible benefit in some individuals. Further,
      larger randomised controlled studies with longer-term follow up are required.

PMID- 19160329
TI  - Antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV in high-risk
      individuals.
AB  - BACKGROUND: Twenty-five years into the global HIV/AIDS epidemic, infection rates
      remain alarmingly high, with over 4 million people becoming infected every year.
      There is a need for HIV prevention strategies that are more effective. Oral
      antiretroviral pre-exposure prophylaxis (PrEP) in high-risk individuals may be a
      reliable tool in preventing the transmission of HIV. OBJECTIVES: To evaluate the
      risk reduction and side effects of antiretroviral chemoprophylaxis in preventing
      HIV infection in high-risk individuals SEARCH STRATEGY: We conducted electronic
      searches of MEDLINE (1980 through June 2008); the Cochrane Central Register of
      Controlled Trials (March 2008); EMBASE (June 2008); and AIDSearch (June 2008). We
      also searched the WHO International Clinical Trials Registry Platform in June
      2008 for ongoing or prospective trials. SELECTION CRITERIA: Randomized controlled
      trials that evaluated the effects of any antiretroviral agent in preventing HIV
      infection in high-risk individuals DATA COLLECTION AND ANALYSIS: Data concerning
      outcomes, details of the interventions, and other study characteristics were
      extracted by two independent authors using a standardized data extraction form.
      The information gathered from each included trial were location of the trial,
      date, publication status, demographics of participants (e.g. age, gender, risk
      behaviour), exposure modality, type of antiretroviral drug used, duration of drug
      use, and outcomes. Relative risk with a 95% confidence interval (CI) was used as
      the measure of effect. Only one trial met our inclusion criteria, so we did not
      perform a meta-analysis. MAIN RESULTS: One randomised controlled trial met the
      criteria for the review, although it was not completed as planned. The trial did
      not have the statistical power to answer questions about the efficacy of
      antiretroviral PrEP for HIV prevention in the assessed risk group. AUTHORS'
      CONCLUSIONS: Presently there is no reliable evidence to support the use of any
      antiretroviral agent for HIV chemoprophylaxis.The value of chemoprophylaxis for
      HIV prevention cannot be assessed on the basis of the included trial. The result
      was not statistically significant and, moreover, the trial was not completed as
      planned; therefore, the use of antiretroviral agents for HIV chemoprophylaxis
      cannot be recommended at present. To assess the value of antiretroviral agents
      for HIV chemoprophylaxis, we advocate well-conducted trials with the statistical
      power to answer questions about PrEP efficacy and safety in various populations
      and risk groups. These trials also should evaluate other important issues of
      concern, such as drug safety, adherence, drug resistance, and the effect of PrEP
      on risk behaviour.

PMID- 19160330
TI  - Theory-based interventions for contraception.
AB  - BACKGROUND: The explicit use of theory in research helps expand the knowledge
      base. Theories and models have been used extensively in HIV-prevention research
      and in interventions for preventing sexually transmitted infections (STIs). The
      health behavior field uses many theories or models of change. However,
      educational interventions addressing contraception often have no stated
      theoretical base. OBJECTIVES: Review randomized controlled trials that tested a
      theoretical approach to inform contraceptive choice; encourage contraceptive use;
      or promote adherence to, or continuation of, a contraceptive regimen. SEARCH
      STRATEGY: We searched computerized databases for trials that tested a theory
      based intervention for improving contraceptive use (MEDLINE, POPLINE, CENTRAL,
      PsycINFO, EMBASE, ClinicalTrials.gov, and ICTRP). We also wrote to researchers to
      find other trials. SELECTION CRITERIA: Trials tested a theory-based intervention
      for improving contraceptive use. We excluded trials focused on high-risk groups.
      Interventions addressed the use of one or more contraceptive methods. The reports
      provided evidence that the intervention was based on a specific theory or model.
      The primary outcomes were pregnancy, contraceptive choice, initiating or changing
      contraceptive use, contraceptive regimen adherence, and contraception
      continuation. DATA COLLECTION AND ANALYSIS: The primary author evaluated
      abstracts for eligibility. Two authors extracted data from included studies. We
      calculated the odds ratio for dichotomous outcomes and the mean difference for
      continuous data. No meta-analysis was conducted due to intervention differences.
      MAIN RESULTS: Of 26 trials, 12 interventions addressed contraception (other than
      condoms), while 14 focused on condom use for preventing HIV or STIs. In 2 of 10
      trials with pregnancy or birth data, a theory-based group showed better results.
      Four of nine trials with contraceptive use (other than condoms) showed better
      outcomes in an experimental group. For condom use, a theory-based group had
      favorable results in 14 of 20 trials, but the number was halved in a subgroup
      analysis. Social Cognitive Theory was the main theoretical basis for 12 trials,
      and 10 showed positive results. Of the other 14 trials, favorable results were
      shown for other social cognition models (N=2), motivational interviewing (N=5),
      and the AIDS Risk Reduction Model (N=2). No major patterns were detected by type
      of theory, intervention, or target population. AUTHORS' CONCLUSIONS: Family
      planning researchers and practitioners could apply the relevant theories and
      effective interventions from HIV and STI prevention. More thorough use of single
      theories would help inform the field about what works. Better reporting is needed
      on research design and intervention implementation.

PMID- 19160331
TI  - Effectiveness of vocational rehabilitation intervention on the return to work and
      employment of persons with multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis is a neurological disease that frequently affects
      adults of working age, resulting in a range of physical, cognitive and
      psychosocial deficits that impact on workforce participation. Although, the
      literature supports vocational rehabilitation (VR) approaches in persons with
      multiple sclerosis (pwMS), the evidence for its effectiveness is yet to be
      established. OBJECTIVES: To evaluate the effectiveness of VR programs compared to
      alternative programs or care as usual on return to work, workability and
      employment in pwMS; to evaluate the cost effectiveness of these programs. SEARCH
      STRATEGY: Electronic searches included: Cochrane Central Register of Controlled
      Trials "CENTRAL" 2008 issue 3, MEDLINE (PubMed) (1966- 2008), EMBASE (1988-
      2008), CINAHL (1982- 2008), PEDro (1990- 2008), the Cochrane Rehabilitation and
      Related Therapies Field trials Register and the National Health Service National
      Research Register. SELECTION CRITERIA: Randomized and controlled clinical trials,
      including before - after controlled trials, that compare VR rehabilitation with
      alternative intervention such as standard or a lesser form of intervention or
      waitlist controls. DATA COLLECTION AND ANALYSIS: Two reviewers selected trials
      and rated their methodological quality independently. A 'best evidence' synthesis
      was performed, based on methodological quality. Trials were grouped in terms of
      type and setting of VR programs. MAIN RESULTS: Two trials (one RCT and one CCT)
      (total 80 participants) met the review criteria. Both trials scored poorly on the
      methodological quality assessment. There was 'insufficient evidence' for VR
      programs for (a)'competitive employment', in altering rates of job retention,
      changes in employment, improvement in rates of re-entry into the labour force;
      (b) for altering 'work ability' by improving participants' confidence in the
      accommodation request process, or employability maturity or job seeking activity.
      No evidence could be assimilated for changes in proportions of persons in
      supported employment or on disability pensions, nor for cost-effectiveness.
      AUTHORS' CONCLUSIONS: There was inconclusive evidence to support VR for pwMS.
      However, the review highlights some of the challenges in providing VR for pwMS.
      Clinicians need to be aware of vocational issues, and to understand and manage
      barriers for maintaining employment. Proactive and timely VR programs should
      incorporate practical solutions to deal with work disability, workplace
      accommodation and educate employers, and the wider community. Liaison with policy
      makers is imperative for government initiatives that encourage work focused VR
      programs. Future research in VR should focus on improving methodological and
      scientific rigour of clinical trials; on the development of appropriate and valid
      outcome measures; and on cost effectiveness of VR programs.

PMID- 19160333
TI  - Disease modifying anti-rheumatic drugs in people with cystic fibrosis-related
      arthritis.
AB  - BACKGROUND: Arthritis remains a relatively infrequent complication of cystic
      fibrosis, but is a cause of significant morbidity when it does occur. Two
      distinct types of arthritis are described in cystic fibrosis: cystic fibrosis
      related arthropathy and hypertrophic osteoarthropathy. Management of arthritis in
      people with cystic fibrosis is uncertain and complex because of the underlying
      disease and its treatment. OBJECTIVES: To review the effectiveness and safety of
      disease-modifying anti-rheumatic drugs (DMARDs) for the management of arthritis
      related to cystic fibrosis in adults and children. SEARCH STRATEGY: We searched
      the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which
      comprises references identified from comprehensive electronic database
      handsearches of relevant journal and abstract books of conference
      proceedings.Date of most recent search: May 2008 SELECTION CRITERIA: Randomised
      controlled trials which compared the efficacy and safety of DMARDs (e.g.
      methotrexate, gold, sulfasalazine, penicillamine, leflunomide, hydroxychloroquine
      and newer agents such as biologic disease modifying agents and monoclonal
      antibodies) with each other, with no treatment or with placebo for cystic
      fibrosis-related arthropathy or hypertrophic osteoarthropathy. DATA COLLECTION
      AND ANALYSIS: No relevant studies were identified. MAIN RESULTS: No studies were
      included in this review. AUTHORS' CONCLUSIONS: Although it is generally
      recognised that cystic fibrosis-related arthritis can be episodic and resolve
      spontaneously, treatment with analgesics and anti-inflammatory agents may be
      needed. But when episodic symptoms progress to persistent disease, DMARDs may be
      needed to limit the course of the disease. It is disappointing that no randomised
      controlled trials to rigorously evaluate DMARDs could be found. This systematic
      review has identified the need for a well-designed adequately powered randomised
      controlled trial to assess the efficacy and safety of DMARDs for the management
      of cystic fibrosis-related arthropathy and hypertrophic osteoarthropathy in
      adults and children with cystic fibrosis. However, given the infrequency of
      cystic fibrosis-related arthritis and the range of symptoms and severity,
      randomised controlled trials may not be feasible and well-designed non-randomised
      observational studies may be more appropriate. Studies should also better define
      the two conditions.

PMID- 19160332
TI  - Intravitreal steroids versus observation for macular edema secondary to central
      retinal vein occlusion.
AB  - BACKGROUND: Central retinal vein occlusion (CRVO) is a common retinal vascular
      abnormality associated with conditions such as hypertension, diabetes, glaucoma,
      and a wide variety of hematologic disorders. Macular edema (ME) represents an
      important vision-threatening complication of CRVO. There is no proven treatment;
      laser photocoagulation is not effective in treating cystoid macular edema
      secondary to CRVO. Intravitreal steroids, such as triamcinolone acetonide, have
      been utilized to treat macular edema stemming from a variety of etiologies and
      may represent a treatment option for CRVO-ME. OBJECTIVES: The objective of this
      review was to explore the effectiveness and safety of intravitreal steroids in
      the treatment of CRVO-ME. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (The Cochrane Library Issue 4, 2008), MEDLINE
      (January 1950 to November 2008) and EMBASE (January 1980 to November 2008). There
      were no language or date restrictions in the search for trials. The electronic
      databases were last searched on 5 November 2008. For all included primary
      studies, we used The Science Citation Index and manually reviewed reference lists
      to identify other possible relevant trials. We contacted researchers in the
      field, currently working on a randomized controlled trial (RCT) on this topic
      (The Standard Care versus Corticosteroid for Retinal Vein Occlusion - SCORE
      study), for information on additional current, past, or unpublished trials.
      SELECTION CRITERIA: We considered RCTs that compared intravitreal steroids of any
      dosage/duration to observation in the treatment of CRVO-ME for inclusion in this
      review. We focused on studies that included individuals of any age or gender with
      unilateral or bilateral disease, with a minimum of six months follow up.
      Secondarily we considered non-randomized studies with the same criteria for
      description of evidence, however we did not conduct a separate electronic search
      for finding all non-randomized studies. DATA COLLECTION AND ANALYSIS: We found no
      RCTs that met the inclusion criteria after independent and duplicate review of
      the search results. MAIN RESULTS: We found no relevant RCTs and therefore
      performed no meta-analysis. Evidence from non-randomized studies is reported in
      this review. AUTHORS' CONCLUSIONS: There is inadequate evidence for the use of
      intravitreal steroids for CRVO-ME due to a paucity of RCTs and well-designed
      observational studies on the topic; therefore, it is still an experimental
      procedure.

PMID- 19160334
TI  - Interventions for treatment of neonatal hyperglycemia in very low birth weight
      infants.
AB  - BACKGROUND: Early neonatal hyperglycemia is common among very low birth weight
      (VLBW) neonates. Increased risks for death and major morbidities have been
      observed among VLBW neonates who develop hyperglycemia. It is uncertain whether
      the hyperglycemia per se is a cause of adverse clinical outcomes or whether the
      incidence of adverse outcomes can be reduced by treatment. OBJECTIVES: To assess
      the effects on clinical outcomes of interventions for treating neonatal
      hyperglycemia in the VLBW neonate receiving total or partial parenteral
      nutrition. SEARCH STRATEGY: We searched The Cochrane Central Register of
      Controlled Trials (CENTRAL), The Cochrane Library, Issue 3, 2008; MEDLINE (1966 -
      July 2008); EMBASE (1980 - July 2008); and CINAHL (1982 - July 2008). We searched
      for abstracts submitted for the annual meetings of The Society for Pediatric
      Research 2000 - 2008 and The European Society for Paediatric Research 2005-2007.
      SELECTION CRITERIA: Randomized or quasi-randomized trials of interventions for
      the treatment of hyperglycemia in hyperglycemic VLBW neonates were eligible for
      inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected studies for eligibility and extracted data on study
      design, methodology, clinical features, and treatment outcomes. Additional
      information on study design and outcomes was obtained from the lead investigator
      of each of the two included trials. The included trials were assessed for
      blinding of randomization, blinding of caretakers to the intervention,
      completeness of follow-up, and blinding of outcome measurement. The treatment
      effect measures for categorical outcomes were relative risk (RR) and risk
      difference (RD) with their 95% confidence intervals (CI); for continuous outcomes
      the measure was mean difference and 95% CI. MAIN RESULTS: Only two eligible
      trials were found (Collins 1991; Meetze 1998). Both were randomized but of very
      small size (24 and 23 neonates randomized in each trial, respectively).No trial
      compared reduction vs. no reduction of glucose infusion.Collins 1991 compared
      insulin infusion with standard care. Insulin infusion had no significant effect
      on death or bacterial sepsis; effects on other major morbidities were not
      assessed. Insulin infusion resulted in significant increases in non-protein
      energy intake, glucose intake, and short-term weight gain.Meetze 1998 compared
      insulin infusion with reduction of glucose infusion. Insulin infusion had no
      significant effects on death, severe intraventricular hemorrhage, retinopathy of
      prematurity, bacterial sepsis, fungal sepsis, or necrotizing enterocolitis;
      effects on other major morbidities were not assessed. Insulin infusion resulted
      in significant increases in glucose intake and total energy intake. AUTHORS'
      CONCLUSIONS: Evidence from randomized trials in hyperglycemic VLBW neonates is
      insufficient to determine the effects of treatment on death or major morbidities.
      It remains uncertain whether the hyperglycemia per se is a cause of adverse
      clinical outcomes or how the hyperglycemia should be treated. Much larger
      randomized trials in hyperglycemic VLBW neonates that are powered on clinical
      outcomes are needed in order to determine whether, and how, the hyperglycemia
      should be treated.

PMID- 19160335
TI  - Botulinum toxin for masseter hypertrophy.
AB  - BACKGROUND: Benign masseter muscle hypertrophy is an uncommon clinical phenomenon
      of uncertain aetiology which is characterised by a soft swelling near the angle
      of the mandible. The swelling may on occasion be associated with facial pain and
      can be prominent enough to be considered cosmetically disfiguring. Varying
      degrees of success have been reported for some of the treatment options for
      masseter hypertrophy, which range from simple pharmacotherapy to more invasive
      surgical reduction. Injection of botulinum toxin type A into the masseter muscle
      is generally considered a less invasive modality and has been advocated for
      cosmetic sculpting of the lower face. Botulinum toxin type A is a powerful
      neurotoxin which is produced by the anaerobic organism Clostridium botulinum and
      when injected into a muscle causes interference with the neurotransmitter
      mechanism producing selective paralysis and subsequent atrophy of the muscle.
      OBJECTIVES: To assess the effects of botulinum toxin type A in the management of
      benign bilateral masseter hypertrophy. SEARCH STRATEGY: We searched the following
      databases in August 2008: the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2008, issue 3); MEDLINE (via PubMed) (1950 to
      August 2008); EMBASE (via embase.com) (1980 to August 2008); and LILACS via
      BIREME. We searched two bibliographic databases of regional journals which may be
      expected to contain relevant trials (IndMED and Iranmedex) using free text terms
      appropriate for this review. SELECTION CRITERIA: Randomised controlled clinical
      trials (RCTs) and controlled clinical trials (CCTs) comparing intra-masseteric
      injections of botulinum toxin versus placebo administered for cosmetic facial
      sculpting in individuals of any age with bilateral benign masseter hypertrophy,
      which had been self-evaluated and confirmed by clinical and radiological
      examination. We excluded participants with unilateral or compensatory
      contralateral masseter hypertrophy resulting from head and neck radiotherapy.
      DATA COLLECTION AND ANALYSIS: Two review authors conducted screening of studies
      in duplicate and independently, and although no eligible trials were identified,
      the two authors had planned to extract data independently and assess trial
      quality using standard Cochrane Collaboration methodologies. MAIN RESULTS: We
      retrieved 167 references to studies, none of which matched the inclusion criteria
      for this review and all of which were excluded. AUTHORS' CONCLUSIONS: We were
      unable to identify any randomised controlled trials on the efficacy of intra
      masseteric injections of botulinum toxin for people with bilateral benign
      masseter hypertrophy. The absence of high level evidence for the effectiveness of
      this intervention emphasises the need for well-designed, adequately powered,
      randomised controlled clinical trials (RCTs) and controlled clinical trials
      (CCTs).

PMID- 19160336
TI  - Vascular occlusion for elective liver resections.
AB  - BACKGROUND: Vascular occlusion is used to reduce blood loss during liver
      resection. There is considerable controversy regarding whether vascular occlusion
      should be used or not during elective liver resections. OBJECTIVES: To assess the
      advantages (decreased blood loss and peri-operative morbidity) and disadvantages
      (ischaemia-reperfusion injury related complications like liver dysfunction) of
      vascular occlusion during elective liver resections. SEARCH STRATEGY: We searched
      The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE,
      EMBASE, and Science Citation Index Expanded until August 2008. SELECTION
      CRITERIA: We included randomised clinical trials comparing vascular occlusion
      versus no vascular occlusion during elective liver resections (irrespective of
      language or publication status). DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trials for inclusion and independently extracted the data.
      We analysed the data with both the fixed-effect and the random-effects models
      using RevMan Analysis. We calculated the risk ratio (RR), mean difference (MD),
      or standardised mean difference (SMD) with 95% confidence intervals (CI) based on
      intention-to-treat or available case analysis. MAIN RESULTS: We identified a
      total of five trials (of high bias-risk) which compared vascular occlusion (n =
      166) versus no vascular occlusion (n = 165). Three of the five trials comparing
      vascular occlusion and no vascular occlusion used intermittent vascular
      occlusion. There was no difference in mortality, liver failure, or other
      morbidities. The blood loss was significantly lower in vascular occlusion
      compared with no vascular occlusion. The liver enzymes were significantly
      elevated in the vascular occlusion group compared with no vascular occlusion.
      AUTHORS' CONCLUSIONS: Intermittent vascular occlusion seems safe in liver
      resection. However, it does not seem to decrease morbidity. More randomised
      trials seem to be needed.

PMID- 19160337
TI  - Humanized antibody to the alpha4beta7 integrin for induction of remission in
      ulcerative colitis.
AB  - BACKGROUND: Cellular adhesion molecules play an important role in the
      pathogenesis of ulcerative colitis, making selective blockade of these molecules
      a promising therapeutic strategy. MLN-02, a recombinant humanized IgG1 monoclonal
      antibody, inhibits adhesion and migration of leukocytes into the gastrointestinal
      tract by binding the alpha4beta7 integrin. Animal studies have suggested that MLN
      02 may be a useful therapy for ulcerative colitis. This systematic review
      summarizes the current evidence on the use of MLN-02 for induction of remission
      in ulcerative colitis. OBJECTIVES: To determine the efficacy and safety of MLN-02
      for induction of remission in ulcerative colitis. SEARCH STRATEGY: A computer
      assisted search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled
      Trials, and the Cochrane Inflammatory Bowel Disease Specialized Trial Register
      was performed to identify relevant publications. References from recent reviews
      and published articles were searched to identify additional citations. Manual
      searches to identify key conference abstracts were performed. Unpublished data
      from on-going trials were identified by correspondence with authors and experts
      in the field and from the manufacturer of MLN-02. SELECTION CRITERIA: Randomized
      controlled trials comparing MLN-02 to placebo or a control therapy for the
      induction of remission in ulcerative colitis were included. DATA COLLECTION AND
      ANALYSIS: Two independent reviewers performed data extraction and assessment of
      the methodological quality of each trial. Data were analyzed using Review Manager
      (RevMan 4.2). MAIN RESULTS: One study satisfied the inclusion criteria for this
      review. In this study, MLN-02 was found to be effective for induction of clinical
      response (RR = 1.78, 95% CI 1.22 to 2.60) and remission (RR = 2.25, 95% CI 1.17
      to 4.36) in patients with moderately severe ulcerative colitis. Patients
      receiving MLN-02 had higher IBDQ scores than patients receiving placebo. There
      was a trend toward increased endoscopic remission with MLN-02 relative to
      placebo, although this difference was not statistically significant (total MLN-02
      20% versus placebo 8%; P = 0.05; RR = 2.46, 95% CI 0.98 to 6.15). Adverse events
      occurred in a similar proportion of patients treated with MLN-02 compared to
      placebo (RR = 1.60, 95% CI 0.67 to 3.83). Neutralizing antibodies were found in a
      significant proportion of patients receiving MLN-02, and in the group of patients
      with high antibody titers clinical remission rates were no different than
      placebo. No opportunistic infections were reported. AUTHORS' CONCLUSIONS: Data
      from one trial suggests that MLN-02 may be effective for induction of clinical
      response and remission in patients with moderately severe ulcerative colitis.
      Adverse events appear to be similar to placebo, although immunogenicity may be an
      issue. Further trials are needed to confirm the results of this study and to
      define the optimal dose and frequency of administration of MLN-02.

PMID- 19160339
TI  - Ischaemic pre-conditioning for elective liver resections performed under vascular
      occlusion.
AB  - BACKGROUND: Vascular occlusion is used to reduce blood loss during liver
      resection surgery. The enzyme markers of liver injury are elevated if vascular
      occlusion is employed during liver resection. It is not clear whether ischaemic
      preconditioning prior to vascular occlusion has a protective effect during
      elective liver resections. OBJECTIVES: To assess the advantages (decreased
      ischaemia-reperfusion injury) and any potential disadvantages of ischaemic
      preconditioning prior to vascular occlusion during liver resections. SEARCH
      STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The
      Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until
      August 2008. SELECTION CRITERIA: We included randomised clinical trials comparing
      ischaemic preconditioning versus no ischaemic preconditioning prior to vascular
      occlusion (irrespective of the method of vascular occlusion) during elective
      liver resections (irrespective of language or publication status). DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed trials for inclusion
      and independently extracted the data. We analysed the data with both the fixed
      effect and the random-effects models using RevMan Analysis. We calculated the
      risk ratio, mean difference, or standardised mean difference with 95% confidence
      intervals based on intention-to-treat or available data analysis. MAIN RESULTS:
      We included four trials with 271 patients undergoing open liver resections. The
      patients were randomised to ischaemic preconditioning (n = 135) and no ischaemic
      preconditioning (n = 136) prior to continuous vascular occlusion (portal triad
      clamping in three trials and hepatic vascular exclusion in one trial). All the
      trials excluded cirrhotic patients. We assessed all the four trials as having
      high risk of bias. There was no difference in mortality, liver failure, other
      peri-operative morbidity, hospital stay, intensive therapy unit stay, and
      operating time between the two groups. The proportion of patients requiring blood
      transfusion was lower in the ischaemic preconditioning group. There was also a
      trend towards a lower amount of red cell transfusion favouring ischaemic
      preconditioning group. There was no difference in the haemodynamic changes, blood
      loss, bilirubin, or prothrombin activity between the two groups. The enzyme
      markers of liver injury were lower in the ischaemic preconditioning group on the
      first post-operative day. AUTHORS' CONCLUSIONS: Currently, there is no evidence
      to suggest a protective effect of ischaemic preconditioning in non-cirrhotic
      patients undergoing liver resection under continuous vascular occlusion.
      Ischaemic preconditioning reduces the blood transfusion requirements in patients
      undergoing liver resection.

PMID- 19160338
TI  - Acupuncture for tension-type headache.
AB  - BACKGROUND: Acupuncture is often used for tension-type headache prophylaxis but
      its effectiveness is still controversial. This review (along with a companion
      review on 'Acupuncture for migraine prophylaxis') represents an updated version
      of a Cochrane review originally published in Issue 1, 2001, of The Cochrane
      Library. OBJECTIVES: To investigate whether acupuncture is a) more effective than
      no prophylactic treatment/routine care only; b) more effective than 'sham'
      (placebo) acupuncture; and c) as effective as other interventions in reducing
      headache frequency in patients with episodic or chronic tension-type headache.
      SEARCH STRATEGY: The Cochrane Pain, Palliative & Supportive Care Trials Register,
      CENTRAL, MEDLINE, EMBASE and the Cochrane Complementary Medicine Field Trials
      Register were searched to January 2008. SELECTION CRITERIA: We included
      randomized trials with a post-randomization observation period of at least 8
      weeks that compared the clinical effects of an acupuncture intervention with a
      control (treatment of acute headaches only or routine care), a sham acupuncture
      intervention or another intervention in patients with episodic or chronic tension
      type headache. DATA COLLECTION AND ANALYSIS: Two reviewers checked eligibility;
      extracted information on patients, interventions, methods and results; and
      assessed risk of bias and quality of the acupuncture intervention. Outcomes
      extracted included response (at least 50% reduction of headache frequency;
      outcome of primary interest), headache days, pain intensity and analgesic use.
      MAIN RESULTS: Eleven trials with 2317 participants (median 62, range 10 to 1265)
      met the inclusion criteria. Two large trials compared acupuncture to treatment of
      acute headaches or routine care only. Both found statistically significant and
      clinically relevant short-term (up to 3 months) benefits of acupuncture over
      control for response, number of headache days and pain intensity. Long-term
      effects (beyond 3 months) were not investigated. Six trials compared acupuncture
      with a sham acupuncture intervention, and five of the six provided data for meta
      analyses. Small but statistically significant benefits of acupuncture over sham
      were found for response as well as for several other outcomes. Three of the four
      trials comparing acupuncture with physiotherapy, massage or relaxation had
      important methodological or reporting shortcomings. Their findings are difficult
      to interpret, but collectively suggest slightly better results for some outcomes
      in the control groups. AUTHORS' CONCLUSIONS: In the previous version of this
      review, evidence in support of acupuncture for tension-type headache was
      considered insufficient. Now, with six additional trials, the authors conclude
      that acupuncture could be a valuable non-pharmacological tool in patients with
      frequent episodic or chronic tension-type headaches.

PMID- 19160340
TI  - Methods of vascular occlusion for elective liver resections.
AB  - BACKGROUND: Vascular occlusion is used to reduce blood loss during liver
      resection surgery. Various methods of vascular occlusion have been suggested.
      OBJECTIVES: To compare the benefits and harms of different methods of vascular
      occlusion during elective liver resection. SEARCH STRATEGY: We searched The
      Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central
      Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE,
      and Science Citation Index Expanded until August 2008. SELECTION CRITERIA: We
      included randomised clinical trials comparing different methods of vascular
      occlusion during elective liver resections (irrespective of language or
      publication status). DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trials for inclusion and independently extracted the data. We calculated
      the risk ratio or mean difference with 95% confidence intervals using fixed
      effect and random-effects models based on intention-to-treat or available data
      analysis. MAIN RESULTS: Ten trials including 657 patients compared different
      methods of vascular occlusion. All trials were of high risk of bias. Only one or
      two trials were included under each comparison. There was no statistically
      significant differences in mortality, liver failure, or other morbidity between
      any of the comparisons.Hepatic vascular occlusion does not decrease the blood
      transfusion requirements. It decreases the cardiac output and increases the
      systemic vascular resistance. In the comparison between continuous portal triad
      clamping and intermittent portal triad clamping, four of the five liver failures
      occurred in patients with chronic liver diseases undergoing the liver resections
      using continuous portal triad clamping. In the comparison between selective
      inflow occlusion and portal triad clamping, all four patients with liver failure
      occurred in the selective inflow occlusion group. There was no difference in any
      of the other important outcomes in any of the comparisons. AUTHORS' CONCLUSIONS:
      In elective liver resection, hepatic vascular occlusion cannot be recommended
      over portal triad clamping. Intermittent portal triad clamping seems to be better
      than continuous portal triad clamping at least in patients with chronic liver
      disease. There is no evidence to support selective inflow occlusion over portal
      triad clamping. The optimal method of intermittent portal triad clamping is not
      clear. There is no evidence for any difference between the ischaemic
      preconditioning followed by vascular occlusion and intermittent vascular
      occlusion for liver resection in patients with non-cirrhotic livers. Further
      randomised trials of low risk of bias are needed to determine the optimal
      technique of vascular occlusion.

PMID- 19160341
TI  - School-based physical activity programs for promoting physical activity and
      fitness in children and adolescents aged 6-18.
AB  - BACKGROUND: The World Health Organization estimates that 1.9 million deaths
      worldwide are attributable to physical inactivity. Chronic diseases associated
      with physical inactivity include cancer, diabetes and coronary heart disease.
      OBJECTIVES: The purpose of this systematic review is to summarize the evidence of
      the effectiveness of school-based interventions in promoting physical activity
      and fitness in children and adolescents. SEARCH STRATEGY: The search strategy
      included searching several databases. In addition, reference lists of included
      articles and background papers were reviewed for potentially relevant studies, as
      well as references from relevant Cochrane reviews. Primary authors of included
      studies were contacted as needed for additional information. SELECTION CRITERIA:
      To be included, the intervention had to be relevant to public health practice,
      implemented, facilitated, or promoted by staff in local public health units,
      implemented in a school setting and aimed at increasing physical activity, report
      on outcomes for children and adolescents (aged 6 to 18 years), and use a
      prospective design with a control group. DATA COLLECTION AND ANALYSIS:
      Standardized tools were used by two independent reviewers to rate each study's
      methodological quality and for data extraction. Where discrepancies existed
      discussion occurred until consensus was reached. The results were summarized
      narratively due to wide variations in the populations, interventions evaluated
      and outcomes measured. MAIN RESULTS: 13,841 titles were identified and screened
      and 482 articles were retrieved. Multiple publications on the same project were
      combined and counted as one project, resulting in 395 distinct project accounts
      (studies). Of the 395 studies 104 were deemed relevant and of those, four were
      assessed as having strong methodological quality, 22 were of moderate quality and
      78 were considered weak. In total 26 studies were included in the review. There
      is good evidence that school-based physical activity interventions have a
      positive impact on four of the nine outcome measures. Specifically positive
      effects were observed for duration of physical activity, television viewing, VO2
      max, and blood cholesterol. Generally school-based interventions had no effect on
      leisure time physical activity rates, systolic and diastolic blood pressure, body
      mass index, and pulse rate. At a minimum, a combination of printed educational
      materials and changes to the school curriculum that promote physical activity
      result in positive effects. AUTHORS' CONCLUSIONS: Given that there are no harmful
      effects and that there is some evidence of positive effects on lifestyle
      behaviours and physical health status measures, ongoing physical activity
      promotion in schools is recommended at this time.

PMID- 19160342
TI  - Galantamine for dementia in people with Down syndrome.
AB  - BACKGROUND: Alzheimer's dementia (AD) is the most common form of dementia in
      people with Down Syndrome (DS). Acetylcholine is a chemical found in the brain
      that has an important role in memory, attention, reason and language. Galantamine
      both inhibits the activity of acetylcholinesterase and increases the level of
      acetylcholine. Galantamine can improve cognitive function and slow the decline of
      AD in the general population over time. It is important to note that people with
      DS tend to present with AD at a much younger age than the normal population as
      well as having subtle differences in physiology (e.g. metabolism and heart rate)
      and may therefore have different requirements from the general population.
      OBJECTIVES: To determine the effectiveness and safety of galantamine for people
      with DS who develop AD. SEARCH STRATEGY: CENTRAL, MEDLINE, EMBASE, CINAHL,
      PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We
      contacted the manufacturers of galantamine as well as experts in the field, to
      ask about reports of unpublished or ongoing trials. SELECTION CRITERIA:
      Randomised controlled trials of participants with DS and AD in which treatment
      with galantamine was administered compared with a placebo group. DATA COLLECTION
      AND ANALYSIS: No study was identified which met inclusion criteria for this
      review. MAIN RESULTS: No study was identified which met inclusion criteria for
      this review. AUTHORS' CONCLUSIONS: As there are no included trials,
      recommendations cannot be made about galantamine for AD in DS. Well-designed,
      adequately powered studies are required.

PMID- 19160343
TI  - Memantine for dementia in people with Down syndrome.
AB  - BACKGROUND: Alzheimer's dementia (AD) is the most common form of dementia in
      people with Down Syndrome (DS). There is an understanding that an increase in L
      glutamate contributes to the pathogenesis of cerebral ischemias and AD. Memantine
      acts as an antagonist of N-methyl-D-aspartate (NMDA) type receptors, which is
      thought to reduce abnormal activation of glutamate neurotransmission. It binds
      with a low affinity to the NMDA receptor and so should not prevent learning and
      the formation of memory. Memantine can improve cognitive function and slow the
      decline of AD in the general population over time, and is the subject of this
      review. It is important to note that people with DS tend to present with AD at a
      much younger age than the normal population as well as having subtle differences
      in physiology (e.g. metabolism and heart rate) and may therefore have different
      requirements from the general population. OBJECTIVES: To determine the
      effectiveness and safety of memantine for people with DS who develop AD. SEARCH
      STRATEGY: CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the
      NRR were searched up to October 2008. We contacted the manufacturers of
      memantine, as well as experts in the field, to ask about reports of unpublished
      or ongoing trials. SELECTION CRITERIA: Randomised controlled trials of
      participants with DS and AD in which treatment with memantine was administered
      compared with a placebo group. DATA COLLECTION AND ANALYSIS: No study was
      identified which met the inclusion criteria for this review. MAIN RESULTS: No
      study was identified which met inclusion criteria for this review, however there
      is an on-going randomised controlled study being conducted in the UK and data are
      expected in 2009. AUTHORS' CONCLUSIONS: As there are no included trials,
      recommendations cannot be made about memantine for AD in DS. Well-designed,
      adequately powered studies are required.

PMID- 19160344
TI  - Rivastigmine for dementia in people with Down syndrome.
AB  - BACKGROUND: Alzheimer's dementia (AD) is the most common form of dementia in
      people with Down Syndrome (DS). Acetylcholine is a chemical found in the brain
      that has an important role in memory, attention, reason and language.
      Rivastigmine is a "pseudo-irreversible" inhibitor of acetylcholinesterase, which
      is thought to maintain levels of acetylcholine. Rivastigmine can improve
      cognitive function and slow the decline of AD in the general population over
      time. It is important to note that people with DS tend to present with AD at a
      much younger age than the normal population as well as having subtle differences
      in physiology (e.g. metabolism and heart rate) and may therefore have different
      requirements from the general population. OBJECTIVES: To determine the
      effectiveness and safety of rivastigmine for people with DS who develop AD.
      SEARCH STRATEGY: CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI
      and the NRR were searched up to October 2008. We contacted the manufacturers of
      rivastigmine as well as experts in the field, to ask about reports of unpublished
      or ongoing trials. SELECTION CRITERIA: Randomised controlled trials of
      participants with DS and AD in which treatment with rivastigmine was administered
      compared with a placebo group. DATA COLLECTION AND ANALYSIS: No study was
      identified which met inclusion criteria for this review. MAIN RESULTS: No study
      was identified which met inclusion criteria for this review. AUTHORS'
      CONCLUSIONS: As there are no included trials, recommendations cannot be made
      about rivastigmine for AD in DS. Well-designed, adequately powered studies are
      required.

PMID- 19160345
TI  - Publication bias in clinical trials due to statistical significance or direction
      of trial results.
AB  - BACKGROUND: The tendency for authors to submit, and of journals to accept,
      manuscripts for publication based on the direction or strength of the study
      findings has been termed publication bias. OBJECTIVES: To assess the extent to
      which publication of a cohort of clinical trials is influenced by the statistical
      significance, perceived importance, or direction of their results. SEARCH
      STRATEGY: We searched the Cochrane Methodology Register (The Cochrane Library
      [Online] Issue 2, 2007), MEDLINE (1950 to March Week 2 2007), EMBASE (1980 to
      Week 11 2007) and Ovid MEDLINE In-Process & Other Non-Indexed Citations (March 21
      2007). We also searched the Science Citation Index (April 2007), checked
      reference lists of relevant articles and contacted researchers to identify
      additional studies. SELECTION CRITERIA: Studies containing analyses of the
      association between publication and the statistical significance or direction of
      the results (trial findings), for a cohort of registered clinical trials. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted data. We classified
      findings as either positive (defined as results classified by the investigators
      as statistically significant (P < 0.05), or perceived as striking or important,
      or showing a positive direction of effect) or negative (findings that were not
      statistically significant (P >/= 0.05), or perceived as unimportant, or showing a
      negative or null direction in effect). We extracted information on other
      potential risk factors for failure to publish, when these data were available.
      MAIN RESULTS: Five studies were included. Trials with positive findings were more
      likely to be published than trials with negative or null findings (odds ratio
      3.90; 95% confidence interval 2.68 to 5.68). This corresponds to a risk ratio of
      1.78 (95% CI 1.58 to 1.95), assuming that 41% of negative trials are published
      (the median among the included studies, range = 11% to 85%). In absolute terms,
      this means that if 41% of negative trials are published, we would expect that 73%
      of positive trials would be published.Two studies assessed time to publication
      and showed that trials with positive findings tended to be published after four
      to five years compared to those with negative findings, which were published
      after six to eight years. Three studies found no statistically significant
      association between sample size and publication. One study found no significant
      association between either funding mechanism, investigator rank, or sex and
      publication. AUTHORS' CONCLUSIONS: Trials with positive findings are published
      more often, and more quickly, than trials with negative findings.

PMID- 19160346
TI  - Sulphate-reducing bacteria and hydrogen sulphide in the aetiology of ulcerative
      colitis.
AB  - BACKGROUND: The aetiology of ulcerative colitis is uncertain but may relate to
      environmental factors in genetically predisposed individuals. Sulphate-reducing
      bacteria (SRB) have been implicated through the harmful effects of hydrogen
      sulphide, a by-product of their respiration. Hydrogen sulphide is freely
      permeable to cell membranes and inhibits butyrate. This review examines the
      available evidence relating to SRB as a possible cause of ulcerative colitis.
      METHODS: A literature search was conducted using the PubMed database and search
      terms 'sulphate reducing bacteria', 'hydrogen sulphide', 'ulcerative colitis',
      'mucous gel layer' and 'trans-sulphuration'. RESULTS: Search results were
      scrutinized and 113 pertinent full-text articles were selected for review.
      Collected data related to hydrogen sulphide metabolism, SRB respiration, mucous
      gel layer composition and their association with ulcerative colitis. CONCLUSION:
      There is evidence to implicate SRB as an environmental factor in ulcerative
      colitis. More sophisticated mucosal dissection and molecular techniques using
      bacteria-directed probes are required to determine an association definitively.

PMID- 19160347
TI  - Determinants of outcome after colorectal resection within an enhanced recovery
      programme.
AB  - BACKGROUND: Postoperative outcomes were studied in relation to adverse
      nutritional risk (body mass index (BMI) below 20 kg/m(2)), advanced age (80 years
      or more) and co-morbidity (American Society of Anesthesiologists (ASA) grade III
      IV) in patients undergoing colorectal resection within an enhanced recovery after
      surgery programme. METHODS: Outcomes were audited prospectively in 1035 patients.
      Morbidity and mortality were compared with those predicted using the Portsmouth
      Physiological and Operative Severity Score for the enUmeration of Mortality and
      morbidity, and a multivariable model was used to determine independent predictors
      of outcome. RESULTS: Postoperative morbidity was lower than predicted (observed
      to expected 0.68; P < 0.001). Independent predictors of delayed mobilization were
      ASA III-IV (P < 0.001) and advanced age (P = 0.025). Prolonged hospital stay was
      related to advanced age (P = 0.002), ASA III-IV (P < 0.001), male sex (P = 0.037)
      and rectal surgery (P < 0.001). Morbidity was related to ASA III-IV (P = 0.004),
      male sex (P = 0.023) and rectal surgery (P = 0.002). None of the factors
      predicted 30-day mortality. CONCLUSION: Age and nutritional status were not
      independent determinants of morbidity or mortality. Pre-existing co-morbidity was
      an independent predictor of several outcomes.

PMID- 19160348
TI  - Territorial belonging of the middle hepatic vein in living liver donor candidates
      evaluated by three-dimensional computed tomographic reconstruction and virtual
      liver resection.
AB  - BACKGROUND: Postoperative venous congestion can lead to graft and remnant liver
      failure in living donor liver transplantation. This study was designed to
      delineate 'territorial belonging' of the middle hepatic vein (MHV) and to
      identify hepatic venous anatomy at high risk of outflow congestion. METHODS: MHV
      belonging patterns for right (RHL) and left (LHL) hemilivers were evaluated by
      three-dimensional computed tomographic reconstruction and virtual hepatectomy in
      138 consecutive living liver donor candidates. RESULTS: The right hepatic vein
      (RHV) was dominant in 84.1 per cent and an accessory inferior hepatic vein (IHV)
      was present in 47.1 per cent of livers. Three MHV belonging types were identified
      for the RHL. Strong and complex MHV types A and C were associated with large RHL
      venous congestion. The MHV belonged to the LHL in 65.9 per cent, draining 37 per
      cent of this hemiliver. In virtual liver resections, left MHV type D was a risk
      category for small left liver remnants. CONCLUSION: MHV territorial belonging
      types A and C were identified as high risk for RHL venous congestion. Their
      presence should prompt consideration of either inclusion of the MHV with the
      right graft or reconstruction of its tributaries, and preservation of IHV
      territory.

PMID- 19160350
TI  - Quality monitoring in thyroid surgery using the Shewhart control chart.
AB  - BACKGROUND: A control chart can help to interpret and reduce sources of
      variability in patient safety by continuously monitoring indicators. The aim of
      this study was to monitor the outcome of thyroid surgery using control charts.
      METHODS: Patients who had thyroid surgery during 2006-2007 were included in the
      study. Safety was monitored based on postoperative complications of recurrent
      laryngeal nerve palsy and hypocalcaemia. Indicators were extracted prospectively
      from the hospital information system and plotted each month on a P-control chart.
      Performance of the surgical team was also measured retrospectively for 2004-2005
      (baseline period) to compare surgical outcomes before and after control chart
      implementation. Electromyographic monitoring of recurrent laryngeal nerves was
      not used, nor was calcium or vitamin D given routinely. RESULTS: The outcomes of
      1114 thyroid procedures were monitored. Although the proportion of patients with
      recurrent laryngeal nerve palsy was similar for baseline and monitored periods
      (6.4 and 7.2 per cent respectively), there was a 35.3 per cent decrease in
      hypocalcaemia after implementation of control charts (P < 0.001). Complications
      almost doubled during a period when one surgeon was away and operating room
      renovations took place. CONCLUSION: Outcome monitoring in thyroid surgery using
      control charts is useful for identifying potential issues in patient safety.

PMID- 19160349
TI  - Systematic review of endoscopic treatments for gastro-oesophageal reflux disease.
AB  - BACKGROUND: The aim of this review was to assess the safety and efficacy of
      endoscopic procedures for gastro-oesophageal reflux disease. METHODS: Literature
      databases including Medline, Embase and PubMed were searched up to May 2006
      without language restriction. Randomized controlled trials and non-randomized
      comparative studies with at least ten patients in each study arm, and case series
      studies of at least ten patients, were included. RESULTS: A total of 33 studies
      examining seven endoscopic procedures (Stretta procedure, Bard EndoCinch, Wilson
      Cook Endoscopic Suturing Device, NDO Plicator, Enteryx, Gatekeeper Reflux Repair
      System and Plexiglas) were included in the review. Of the three procedures that
      were tested against sham controls (Stretta procedure, Bard EndoCinch and
      Enteryx), patient outcomes in the treatment group were either as good as, or
      significantly better than, those of control patients in terms of heartburn
      symptoms, quality of life and medication usage. However, for the two procedures
      that were tested against laparoscopic fundoplication (Stretta) procedure and Bard
      EndoCinch), outcomes for patients in the endoscopic group were either as good as,
      or inferior to, those for the laparoscopic group. CONCLUSION: At present there is
      insufficient evidence to determine the safety and efficacy of endoscopic
      procedures for gastro-oesophageal reflux disease, particularly in the long term.

PMID- 19160351
TI  - Proteoglycan production is required in initial stages of new cartilage matrix
      formation but inhibits integrative cartilage repair.
AB  - The optimal stimulus to repair or regenerate cartilage is not known. We therefore
      modulated collagen deposition, collagen crosslinking and GAG deposition
      simultaneously during cartilage matrix production and integrative repair,
      creating more insight into their role in cartilage repair processes. Insulin-like
      growth factor 1 (IGF-1; increases proteoglycan and collagen synthesis), beta
      aminopropionitrile (BAPN; a reversible inhibitor of collagen crosslinking) and
      para-nitrophenyl-beta-D-xyloside (PNPX; interferes with proteoglycan production)
      were used. Bovine articular chondrocytes were cultured in alginate beads for 3
      weeks with or without IGF-1, BAPN or PNPX alone and in all possible combinations,
      followed by 3 weeks in control medium. DNA content, GAG and collagen deposition
      and collagen crosslinks were determined. Cartilage constructs were cultured under
      the same conditions and histologically analysed for integration of two opposing
      cartilage matrices. In alginate cultures, inhibition of collagen crosslinking
      with BAPN, in combination with promotion of matrix synthesis using IGF1, was most
      beneficial for matrix deposition. Addition of PNPX was always detrimental for
      matrix deposition. For integration of opposing cartilage constructs, the
      combination of BAPN, IGF1 and temporary prevention of proteoglycan formation with
      PNPX was most beneficial. When a new matrix is produced, proteoglycans are
      important to retain collagen in the matrix. When two already formed cartilage
      matrices have to integrate, a temporary absence of proteoglycans and temporary
      inhibition of collagen crosslinking might be more beneficial in combination with
      stimulation of collagen production, e.g. by IGF1. Therefore, the choice of
      soluble factors to promote cartilage regeneration depends on the type of therapy
      that will be used.

PMID- 19160352
TI  - G-SIMS: relative effectiveness of different monatomic primary ion source
      combinations.
AB  - An analysis is made of the characteristics of monatomic primary ion sources to
      generate G-SIMS (gentle SIMS) spectra. In previous studies, this is resolved into
      the parameter beta that describes the relative intensities of ions in the series
      C(n)H(n+2-i) as i changes. For this, data from polystyrene are most extensive. It
      is found that the experimental beta values, which relate to the emitted secondary
      ion fragment surface plasma temperatures, are accurately described by an
      empirical fit involving the ratio of the sputtering yield and the mass of the
      primary ion. This description covers data for Ar(+), Bi(+), Cs(+), Ga(+), Mn(+)
      and Xe(+) monatomic primary ions with energies in the range 4 to 25 keV, placing
      them in a coherent framework, and permits the performance of any other monatomic
      primary ion to be predicted. This shows that, of all monatomic primary ions, Bi
      will yield the highest beta values and Mn the lowest. Since the G-SIMS spectra
      are ratios, a ratio involving spectra using these primary ions gives the maximum
      signal quality possible and these are therefore recommended for use. The previous
      choice of these ions for a combined G-SIMS source, based on practical
      considerations, is thus shown to be optimum.

PMID- 19160354
TI  - Systematic review of randomized controlled trials on the effectiveness of virtual
      reality training for laparoscopic surgery (Br J Surg 2008; 95: 1088-1097).

PMID- 19160356
TI  - Clinical and non-clinical factors influencing postoperative health-related
      quality of life in patients with colorectal cancer (Br J Surg 2008; 95: 1408
      1415).

PMID- 19160358
TI  - Randomized clinical trial of groin hernia repair with titanium-coated lightweight
      mesh compared with standard polypropylene mesh (Br J Surg 2008; 95: 1226-1231).

PMID- 19160360
TI  - Non-operative management of rectal cancer after neoadjuvant chemoradiation.

PMID- 19160361
TI  - Treatment of liver metastases from neuroendocrine tumours in relation to the
      extent of hepatic disease.
AB  - BACKGROUND: Hepatic surgery is presumed to improve survival of patients with
      liver metastases (LM) from neuroendocrine tumours (NET). This study identified LM
      specific variables that could be used as additional selection criteria for
      aggressive treatment. METHODS: A novel classification of LM from NET was
      established based on their localization and presentation. RESULTS: From 1992 to
      2006, 119 patients underwent staging and treatment of LM. Three growth types of
      LM were identified radiologically: single metastasis (type I), isolated
      metastatic bulk accompanied by smaller deposits (type II) and disseminated
      metastatic spread (type III). The three groups differed significantly in terms of
      chronological presentation of LM, hormonal symptoms, Ki-67 index, 5
      hydroxyindoleacetic acid and chromogranin A levels, lymph node involvement,
      presence of bone metastases and treatment options. The 3-, 5- and 10-year disease
      specific survival rates for the entire cohort were 76.4, 63.9 and 46.5 per cent
      respectively. There were significant differences in survival between the three
      groups: 5- and 10-year rates were both 100 per cent for type I, 84 and 75 per
      cent respectively for type II, and 51 and 29 per cent for type III. CONCLUSION:
      The localization and biological features of LM from NET defines therapeutic
      management and is predictive of outcome.

PMID- 19160362
TI  - Intravenous fluid therapy.

PMID- 19160363
TI  - Laparoscopic management of insulinomas.
AB  - BACKGROUND: Conventional surgical management of insulinomas involves an open
      technique. The laparoscopic approach has advantages in terms of improved
      postoperative pain and recovery time. This retrospective study evaluated the
      laparoscopic management of pancreatic insulinomas. METHODS: Between December 2000
      and March 2007, 23 patients were referred for consideration of laparoscopic
      insulinoma resection. Two patients were not deemed appropriate for the
      laparoscopic approach and were managed with open surgery. All surgery was
      performed by one experienced pancreatic surgeon. Laparoscopic intraoperative
      ultrasonography was not available for the first six procedures, but was used
      thereafter. RESULTS: Twenty-one patients (five men and 16 women, median age 46
      (range 22-70) years) had a successful resection. All had single tumours, five in
      the head, nine in the body and seven in the tail of the pancreas. One conversion
      to open operation was performed in a patient with an insulinoma in the head of
      the pancreas who had dense adhesions resulting from pancreatitis. Three patients
      developed a postoperative pancreatic fistula. There has been no recurrence of
      symptoms in any patient. CONCLUSION: Laparoscopic management of insulinomas is
      feasible and safe. Laparoscopic intraoperative ultrasonography is a promising
      adjunct to the procedure, even after accurate preoperative localization.

PMID- 19160364
TI  - Composite abdominosacral resection for recurrent rectal cancer.
AB  - BACKGROUND: En bloc resection of the tumour and adjacent involved organs offers
      the only realistic curative option for patients with locally recurrent rectal
      cancer. This study assessed outcomes of composite resection for recurrent tumours
      involving the sacrum. METHODS: A consecutive series of patients underwent
      composite abdominosacral resection (abdominal mobilization and stoma construction
      followed by sacral division and tumour retrieval) for recurrent rectal cancer
      between 2001 and 2007. Patients were staged with preoperative computed
      tomography, magnetic resonance imaging and positron emission tomography. Data
      were collected prospectively. RESULTS: Forty patients (28 men; median age 59
      (range 31-77) years) underwent surgery with sacral division at the S2/3 interface
      in 13, S3/4 level in 20 and S4/5 level in seven patients. One patient died and 24
      had complications. An R0 resection was achieved in 20 patients and conferred
      benefit in disease-free interval over an R1 resection. The mean disease-free
      interval was 55.6 (95 per cent confidence interval (c.i.) 40.0 to 71.3) months
      for R0 and 32.2 (95 per cent c.i. 19.7 to 44.7) months for R1 resection (P =
      0.048). CONCLUSION: Composite abdominosacral resection of locally recurrent
      rectal cancer is an effective treatment for a difficult clinical scenario.

PMID- 19160365
TI  - Association between [18F]fluorodeoxyglucose uptake and prognostic parameters in
      breast cancer.
AB  - BACKGROUND: This study analysed the correlation between [(18)F]fluorodeoxyglucose
      (FDG) uptake assessed by positron emission tomography (PET) in breast tumours,
      and histopathological and inmunohistochemical prognostic factors. METHODS: FDG
      PET was performed before surgery in 275 women with primary breast cancer. The
      standarized uptake value (SUV) was compared with histopathological findings after
      surgery. RESULTS: A positive relationship was found between the SUV and tumour
      size (r = 0.46, P < 0.001), axillary lymph node status (P < 0.001), histological
      type (P < 0.001), histological grade (P < 0.001), oestrogen receptor status (P <
      0.001), p53 (P < 0.001) and Ki-67 (P < 0.001) expression. Multivariable linear
      regression showed that tumour size, histological grade, Ki-67 expression,
      oestrogen receptor status and histological type were significantly related to the
      SUV. CONCLUSION: The SUV is a preoperative and non-invasive metabolic factor that
      relates to some prognostic factors in breast cancer.

PMID- 19160366
TI  - Randomized clinical trial of a modified Seldinger technique for open central
      venous cannulation for implantable access devices.
AB  - INTRODUCTION: Totally implantable access ports (TIAPs) are often used for
      patients who need permanent venous access. The primary success rate using direct
      open insertion is about 80 per cent, so rescue strategies are needed. This study
      compared the primary success rates of standard open insertion and a modified
      Seldinger technique. METHODS: This randomized trial recruited 164 patients
      scheduled for primary implantation of a TIAP and compared two interventions. The
      primary endpoint was the success rate of the implantation technique. RESULTS: The
      primary success rates were similar: 66 (80 per cent) of 82 patients who had
      standard open insertion versus 69 (84 per cent) of 82 patients undergoing the
      modified Seldinger method (P = 0.686). A logistic mixed regression analysis
      including treatment group, age, Karnofsky index, body mass index and surgeon's
      experience showed no advantage for the Seldinger method: odds ratio 1.30 (95 per
      cent confidence interval 0.62 to 2.70). TIAPs were eventually implanted
      successfully in 163 (99.4 per cent) of 164 patients. In 11 patients randomized to
      standard surgery, the Seldinger method was a successful rescue strategy.
      CONCLUSION: The primary success rate was similar for both open insertion methods.
      The modified Seldinger method is useful if standard open insertion fails.
      REGISTRATION NUMBER: ISRCTN 52368201 (http://www.controlled-trials.com).

PMID- 19160367
TI  - Electrical stimulation induces propagated colonic contractions in an experimental
      model.
AB  - BACKGROUND: Direct colonic electrical stimulation may prove to be a treatment
      option for specific motility disorders such as chronic constipation. The aim of
      this study was to provoke colonic contractions using electrical stimulation
      delivered from a battery-operated device. METHODS: Electrodes were inserted into
      the caecal seromuscular layer of eight anaesthetized pigs. Contractions were
      induced by a neurostimulator (Medtronic 3625). Caecal motility was measured
      simultaneously by video image analysis, manometry and a technique assessing
      colonic transit. RESULTS: Caecal contractions were generated using 8-10 V
      amplitude, 1000 micros pulse width, 120 Hz frequency for 10-30 s, with an
      intensity of 7-15 mA. The maximal contraction strength was observed after 20-25
      s. Electrical stimulation was followed by a relaxation phase of 1.5-2 min during
      which contractions propagated orally and aborally over at least 10 cm.
      Spontaneous and stimulated caecal motility values were significantly different
      for both intraluminal pressure (mean(s.d.) 332(124) and 463(187) mmHg
      respectively; P < 0.001, 42 experiments) and movement of contents (1.6(0.9) and
      3.9(2.8) mm; P < 0.001, 40 experiments). CONCLUSION: Electrical stimulation
      modulated caecal motility, and provoked localized and propagated colonic
      contractions.

PMID- 19160368
TI  - Determination and quantification of astragalosides in Radix Astragali and its
      medicinal products using LC-MS.
AB  - In the present study, a liquid chromatography-tandem mass spectrometry method was
      developed for the separation and simultaneous quantification of astragalosides I
      IV in samples of Radix Astragali and a medicinal product thereof (Jinqi Jiangtang
      tablets). Chromatographic separation was achieved on an Agilent Eclipse XDB (ODS)
      C18 column with a mobile phase consisting of acetonitrile and 0.05% formic acid
      aqueous solution by use of an efficient 17-min program. A triple quadrupole mass
      spectrometer was operated in positive ionization mode with multiple reaction
      monitoring for the detection of four astragalosides. The saponin ginsenoside Rg1
      (similar structure to astralagosides) was used as an internal standard. All
      calibration curves showed excellent linear regressions (r(2) greater, not dbl
      equals 0.9912) within the range of tested concentrations. The intra- and inter
      day variations were below 4.57% in terms of RSD. The recoveries were 94.38
      103.53% with RSD of 1.39-3.58% for spiked Radix Astragali samples. The method was
      successfully used for the analysis of samples of Radix Astragali and Jinqi
      Jiangtang tablets. In conclusion, we have developed a rapid, efficient, and
      accurate LC-MS/MS method for the detection of astragalosides, which can be
      applied for quality control of Radix Astragali and related medicinal products.

PMID- 19160369
TI  - Potential of long capillary monolithic columns for the analysis of protein
      digests.
AB  - The gain in separation efficiency for protein digests using long monolithic
      columns has been evaluated for a LC-MS system with capillary monolithic columns
      of different lengths (150 and 750 mm). A mixture of BSA, alpha-casein and beta
      casein tryptic digests was used as a test sample. Peak capacity and productivity
      (peak capacity per unit time) were determined from base peak chromatograms and
      MS/MS data were used for protein identification by MASCOT database searching.
      Peak capacity and protein identification scores were higher for the long column.
      Analyses with similar gradient slope for the two columns produced ratios of the
      peak capacities that were slightly higher than the expected value of the square
      root of the column length ratio. Peak capacity ratios varied from 2.7 to 4.0 for
      four different gradient slopes, while protein identification scores were 2-4
      times higher for the long column. Similar values were obtained for the
      productivity of both columns and the highest productivity was obtained at
      gradient times of 45 and 75 min for the short and long column, respectively. The
      use of long monolithic columns improves peptide separation and increases
      reliability of protein identification for complex digests, especially if longer
      gradients are chosen.

PMID- 19160370
TI  - Validation of green-solvent extraction combined with chromatographic chemical
      fingerprint to evaluate quality of Stevia rebaudiana Bertoni.
AB  - An approach that combined green-solvent methods of extraction with
      chromatographic chemical fingerprint and pattern recognition tools such as
      principal component analysis (PCA) was used to evaluate the quality of medicinal
      plants. Pressurized hot water extraction (PHWE) and microwave-assisted extraction
      (MAE) were used and their extraction efficiencies to extract two bioactive
      compounds, namely stevioside (SV) and rebaudioside A (RA), from Stevia rebaudiana
      Bertoni (SB) under different cultivation conditions were compared. The proposed
      methods showed that SV and RA could be extracted from SB using pure water under
      optimized conditions. The extraction efficiency of the methods was observed to be
      higher or comparable to heating under reflux with water. The method precision
      (RSD, n = 6) was found to vary from 1.91 to 2.86% for the two different methods
      on different days. Compared to PHWE, MAE has higher extraction efficiency with
      shorter extraction time. MAE was also found to extract more chemical constituents
      and provide distinctive chemical fingerprints for quality control purposes. Thus,
      a combination of MAE with chromatographic chemical fingerprints and PCA provided
      a simple and rapid approach for the comparison and classification of medicinal
      plants from different growth conditions. Hence, the current work highlighted the
      importance of extraction method in chemical fingerprinting for the classification
      of medicinal plants from different cultivation conditions with the aid of pattern
      recognition tools used.

PMID- 19160371
TI  - Poly(N,N-dimethylacrylamide-co-4-(ethyl)-morpholine methacrylamide) copolymer as
      coating for CE.
AB  - In this work, a new physically adsorbed coating for CE is presented. This coating
      is based on a poly(N,N-dimethylacrylamide-co-4-(ethyl)-morpholine methacrylamide)
      (DMA/MAEM) copolymer synthesized in our laboratory. It is demonstrated that the
      direction and magnitude of the EOF in CE can be modulated by varying the
      composition of the DMA/MAEM copolymer and the type and pH of the BGE. Moreover,
      the DMA/MAEM coating provides %RSD(n) = 5 values for migration times lower than
      0.9% for the same capillary and day, whereas the %RSD(n) = 25 obtained for the
      interday assay was lower than 2.9%. The stability of the coating procedure is
      also tested between capillaries obtaining %RSD(n) = 15 values lower than 2.9%,
      demonstrating that this physically adsorbed copolymer gives rise to a stable and
      reproducible coating in CE. Finally, the usefulness of this new cationic
      copolymer as CE coating is demonstrated through different applications. Namely,
      it is demonstrated that the CE separation of basic proteins, nucleotides and
      organic acids is achieved in a fast and easy way by using the DMA/MAEM coated
      capillary. The use of fused bare silica capillaries did not allow the separation
      of these compounds under the same analytical conditions. These results
      demonstrate that this type of coating in CE provides the option of using BGEs
      that are useless when utilized together with bare silica capillaries making wider
      the application and possibilities of this analytical technique.

PMID- 19160373
TI  - 3D culture of osteoblast-like cells by unidirectional or oscillatory flow for
      bone tissue engineering.
AB  - A medium perfusion system is expected to be beneficial for three-dimensional (3D)
      culture of engineered bone, not only by chemotransport enhancement but also by
      mechanical stimulation. In this study, perfusion systems with either
      unidirectional or oscillatory medium flow were developed, and the effects of the
      different flow profiles on 3D culturing of engineered bone were studied. Mouse
      osteoblast-like MC 3T3-E1 cells were 3D-cultured with porous ceramic scaffolds in
      vitro for 6 days under static and hydrodynamic conditions with either a
      unidirectional or oscillatory flow. We found that, in the static culture, the
      cells proliferated only on the scaffold surfaces. In perfusion culture with the
      unidirectional flow, the proliferation was significantly higher than in the other
      groups but was very inhomogeneous, which made the construct unsuitable for
      transplantation. Only the oscillatory flow allowed osteogenic cells to
      proliferate uniformly throughout the scaffolds, and also increased the activity
      of alkaline phosphatase (ALP). These results suggested that oscillatory flow
      might be better than unidirectional flow for 3D construction of cell-seeded
      artificial bone. The oscillatory perfusion system could be a compact, safe, and
      efficient bioreactor for bone tissue engineering.

PMID- 19160372
TI  - Effect of quasi-interpenetrating network of polyacrylamide and poly(N,N
      dimethylacrylamide) on separation of dsDNA fragments and basic protein using CE.
AB  - Quasi-interpenetrating network (quasi-IPN) of linear polyacrylamide (LPA) with
      low molecular mass and poly(N,N-dimethylacrylamide) (PDMA), which is shown to
      uniquely combine the superior sieving ability of LPA with the coating ability of
      PDMA, has been synthesized for application in dsDNA and basic protein separation
      by CE. The performance of quasi-IPN on dsDNA separation was determined by polymer
      concentration, electric field strength, LPA molecular masses and different
      acrylamide (AM) to N,N-dimethylacrylamide (DMA) ratio. The results showed that
      all fragments in Phix174/HaeIII digest were achieved with a 30 cm effective
      capillary length at -6 kV at an appropriate polymer solution concentration in
      bare silica capillaries. Furthermore, EOF measurement results showed that quasi
      IPN exhibited good capillary coating ability, via adsorption from aqueous
      solution, efficiently suppressing EOF. The effect of the buffer pH values on the
      separation of basic proteins was investigated in detail. The separation
      efficiencies and analysis reproducibility demonstrated the good potentiality of
      quasi-IPN matrix for suppressing the adsorption of basic proteins onto the silica
      capillary wall. In addition, when quasi-IPN was used both as sieving matrix and
      dynamic coating in bare silica capillaries, higher peak separation efficiencies,
      and better migration time reproducibility were obtained.

PMID- 19160374
TI  - Prediction of supercritical fluid chromatographic retention factors at different
      percents of organic modifiers in mobile phase.
AB  - In this work quantitative structure-retention relationship models were developed
      to predict the solute retention factors in supercritical fluid chromatography
      (SFC) in various organic modifiers. Data set contains the retention data of 35
      various organic compounds in 0, 2, 4 and 6% of methanol in mobile phase. The
      obtained 140 data points were divided into training, internal and external test
      sets which have 93, 23 and 24 retention data. The diversity validation test was
      performed on data the set to ensure that the structure of the training and/or
      test sets can represent those of the whole ones. Descriptors which were selected
      by stepwise multiple linear regression (MLR) methods are: the percent of organic
      modifier in mobile phase, salvation connectivity index chi-2, salvation
      connectivity index chi-5, H attached to heteroatom, the 2(nd) structural
      information content and polarity parameter. These descriptors were used as
      features in generation of linear and non-linear models using MLR and artificial
      neural network (ANN) methods, respectively. The root mean square error of MLR
      model are 0.116, 0.138 and 0.260 for training, internal and external test sets,
      respectively, while these values are 0.036, 0.097 and 0.244 for ANN model,
      respectively. Comparison between these values and other statistical parameters
      obtained from these two models reveals the credibility of ANN in prediction of
      solute retention factors in SFC.

PMID- 19160375
TI  - Yield and physicochemical properties of EPS from Halomonas sp. strain TG39
      identifies a role for protein and anionic residues (sulfate and phosphate) in
      emulsification of n-hexadecane.
AB  - In this study, we investigated the yield and physicochemical properties of the
      high molecular weight extracellular polymeric substance (HMW-EPS) produced by
      Halomonas sp. strain TG39 when grown on different types and ratios of substrates.
      Glucose (1% w/v) and a peptone/yeast extract ratio of 5.1 (0.6% w/v final
      concentration) yielded an EPS fraction (HMW-glucose) exhibiting the highest
      anionic activity (20.5) and specific emulsifying activity (EI24 = 100%) compared
      to EPS produced by cells grown on mannitol, sucrose, malt extract or no carbon
      source. The HMW-EPS fractions were capable of binding approximately 255-464 mg of
      methylene blue (MB) per gram of EPS, which represents the highest reported
      binding of MB by a bacterial EPS. A comparative evaluation of these properties to
      those of commercial hydrocolloids indicated that the combined effect of protein
      and anionic residues of the HMW-EPS contributed to its ability to emulsify n
      hexadecane. Liquid chromatography revealed the HMW-glucose EPS to be a
      heterogeneous polymer with a polydispersity index of 1.8. This work presents
      evidence of a correlation between the anionic nature and protein content of
      bacterial EPS with its emulsifying qualities, and identifies EPS produced by
      strain TG39 as a high MB-binding bacterial sorbant with potential
      biotechnological application.

PMID- 19160376
TI  - HPLC of fluoroquinolone antibacterials using chiral stationary phase based on
      enantiomeric (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6.
AB  - A residual silanol group-protecting chiral stationary phase (CSP) based on
      optically active (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 was successfully
      applied to the resolution of fluoroquinolone compounds including gemifloxacin
      mesylate. The chiral recognition ability of the residual silanol group-protecting
      CSP was generally greater than that of the residual silanol group-containing CSP.
      From these results, it was concluded that the simple protection of the residual
      silanol groups of the latter CSP with lipophilic n-octyl groups can improve its
      chiral recognition ability for the resolution of racemic fluoroquinolone
      compounds. The chromatographic resolution behaviors were investigated as a
      function of the content and type of organic and acidic modifiers and the ammonium
      acetate concentration in aqueous mobile phase and the column temperature.
      Especially, the addition of ammonium acetate to the mobile phase was found to be
      a quite effective means of reducing the enantiomer retentions without sacrificing
      the chiral recognition efficiency of the CSP.

PMID- 19160377
TI  - Sensitivity enhancement in tandem liquid chromatographic mass spectrometric
      assays by summation of two transition ion pairs--perspectives.
AB  - The introduction of tandem liquid chromatographic mass spectrometric assays has
      boosted the sensitivity of the bioanalytical determination for the scores of
      analytes as compared to other conventional modes of detection [1-6].
      Additionally, many intelligent variants such as improved ionization potential,
      suitable adduct formation, and/or identification of a precursor ion, switching of
      modality of detection (+ve to -ve and vice versa), and derivatization steps (to
      aid fragmentation and/or impart ionization property) within tandem mass
      spectrometric assays have further aided in improving the sensitivity. Some
      researchers have also expressed thoughts of using matrix effects in a beneficial
      manner so that there may be ion enhancement for improving the sensitivity of the
      assay.

PMID- 19160378
TI  - Microbial reductive dechlorination of trichloroethene to ethene with electrodes
      serving as electron donors without the external addition of redox mediators.
AB  - In situ bioremediation of industrial chlorinated solvents, such as
      trichloroethene (TCE), is typically accomplished by providing an organic electron
      donor to naturally occurring dechlorinating populations. In the present study, we
      show that TCE dechlorinating bacteria can access the electrons required for TCE
      dechlorination directly from a negatively polarized (-450 mV vs. SHE) carbon
      paper electrode. In replicated batch experiments, a mixed dechlorinating culture,
      also containing Dehalococcoides spp., dechlorinated TCE to cis-dichloroethene
      (cis-DCE) and lower amounts of vinyl chloride (VC) and ethene using the polarized
      electrode as the sole electron donor. Conversely, neither VC nor ethene formation
      occurred when a pure culture of the electro-active microorganism Geobacter
      lovleyi was used, under identical experimental conditions. Cyclic voltammetry
      tests, carried out on the filter-sterilized supernatant of the mixed culture
      revealed the presence of a self-produced redox mediator, exhibiting a midpoint
      potential of around -400 mV (vs. SHE). This yet unidentified redox-active
      molecule appeared to be involved in the extracellular electron transfer from the
      electrode to the dechlorinating bacteria. The ability of dechlorinating bacteria
      to use electrodes as electron donors opens new perspectives for the development
      of clean, versatile, and efficient bioremediation systems based on a controlled
      subsurface delivery of electrons in support of biodegradative metabolisms and
      provides further evidence on the possibility of using conductive materials to
      manipulate and control a range of microbial bioprocesses.

PMID- 19160379
TI  - Compensatory ability to null mutation in metabolic networks.
AB  - Robustness is an inherent property of biological system. It is still a limited
      understanding of how it is accomplished at the cellular or molecular level. To
      this end, this article analyzes the impact degree of each reaction to others,
      which is defined as the number of cascading failures of following and/or forward
      reactions when an initial reaction is deleted. By analyzing more than 800
      organism's metabolic networks, it suggests that the reactions with larger impact
      degrees are likely essential and the universal reactions should also be
      essential. Alternative metabolic pathways compensate null mutations, which
      represents that average impact degrees for all organisms are small.
      Interestingly, average impact degrees of archaea organisms are smaller than other
      two categories of organisms, eukayote and bacteria, indicating that archaea
      organisms have strong robustness to resist the various perturbations during the
      evolution process. The results show that scale-free feature and reaction
      reversibility contribute to the robustness in metabolic networks. The optimal
      growth temperature of organism also relates the robust structure of metabolic
      network.

PMID- 19160380
TI  - The dynamics of surface acoustic wave-driven scaffold cell seeding.
AB  - Flow visualization using fluorescent microparticles and cell viability
      investigations are carried out to examine the mechanisms by which cells are
      seeded into scaffolds driven by surface acoustic waves. The former consists of
      observing both the external flow prior to the entry of the suspension into the
      scaffold and the internal flow within the scaffold pores. The latter involves
      micro-CT (computed tomography) scans of the particle distributions within the
      seeded scaffolds and visual and quantitative methods to examine the morphology
      and proliferation ability of the irradiated cells. The results of these
      investigations elucidate the mechanisms by which particles are seeded, and hence
      provide valuable information that form the basis for optimizing this recently
      discovered method for rapid, efficient, and uniform scaffold cell seeding. Yeast
      cells are observed to maintain their size and morphology as well as their
      proliferation ability over 14 days after they are irradiated. The mammalian
      primary osteoblast cells tested also show little difference in their viability
      when exposed to the surface acoustic wave irradiation compared to a control set.
      Together, these provide initial feasibility results that demonstrate the surface
      acoustic wave technology as a viable seeding method without risk of denaturing
      the cells.

PMID- 19160381
TI  - Ultra scale-down of protein refold screening in microwells: challenges, solutions
      and application.
AB  - Steps for the refolding of proteins from solubilized inclusion bodies or
      misfolded product often represent bottlenecks in process development, where
      optimal conditions are typically derived empirically. To expedite refolding
      optimization, microwell screening may be used to test multiple conditions in
      parallel. Fast, accurate, and reproducible assays are required for such screening
      processes, and the results derived must be representative of the process at full
      scale. This article demonstrates the use of these microscale techniques to
      evaluate the effects of a number of additives on the refolding of IGF-1 from
      denatured inclusion bodies, using an established HPLC assay for this protein.
      Prior to this, microwell refolding was calibrated for scale-up using hen egg
      white lysozyme (HEWL) as an initial model protein, allowing us to implement and
      compare several assays for protein refolding, including turbidity, enzyme
      activity, and chromatographic methods, and assess their use for microwell-based
      experimentation. The impact of various microplate types upon protein binding and
      loss is also assessed. Solution mixing is a key factor in protein refolding,
      therefore we have characterized the effects of different methods of mixing in
      microwells in terms of their impact on protein refolding. Our results confirm the
      applicability and scalability of microwell screening for the development of
      protein refolding processes, and its potential for application to new inclusion
      body-derived protein products.

PMID- 19160382
TI  - Inactivation of 14-3-3 sigma by promoter methylation correlates with metastasis
      in nasopharyngeal carcinoma.
AB  - 14-3-3 sigma, the downstream target of p53, is a negative regulator of cell cycle
      G2-M phase checkpoint in response to DNA damage. Our previous comparative
      proteomics study showed that 14-3-3 sigma was downregulated or lost in
      nasopharyngeal carcinoma (NPC) tissue compared with non-cancerous nasopharyngeal
      epithelial tissue (NNET). In this study, we further investigated for the
      epigenetic mechanism of 14-3-3 sigma inactivation. Methylation-specific PCR
      showed 14-3-3 sigma promoter methylation in 100% of analyzed NPC cell lines (4/4)
      but not in immortalized human nasopharyngeal epithelial cell line NP69. Treatment
      of the four NPC cell lines with the methyltransferase inhibitor 5-aza-2'-dC
      resulted in the demethylation and upregulation of 14-3-3 sigma. In tissues, 14-3
      3 sigma promoter methylation occurred at a higher frequency in NPC, 63/75 (84%),
      compared to adjacent NNET, 7/25 (28%), and fully methylated 14-3-3 sigma promoter
      was detected in NPC but not in any of adjacent NNET. RT-PCR, Western blotting,
      and immunohistochemistry showed that 14-3-3 sigma expression was downregulated or
      lost in NPC with methylation, and there was a negative correlation between the
      expression levels and methylation statuses of 14-3-3 sigma gene. In addition, the
      patients with methylated 14-3-3 sigma presented a higher frequency of lymph node
      and distant metastasis, and an advanced clinical stage, and overexpression of 14
      3-3 sigma in NPC cell line 5-8F with high metastatic potential was able to
      inhibit its in vitro invasive ability. Our data are the first to show that 14-3-3
      sigma is frequently inactivated by promoter methylation in NPC and this aberrant
      methylation correlates with lymph node and distant metastasis.

PMID- 19160384
TI  - Neuromonitoring of the external branch of the superior laryngeal nerve during
      minimally invasive thyroid surgery under local anesthesia: a prospective study of
      10 patients.
AB  - OBJECTIVES/HYPOTHESIS: Avoiding alterations of the voice is a challenge in
      thyroid surgery. Identification and preservation of the external branch of the
      superior laryngeal nerve (EBSLN) is paramount for normal vocal function
      preservation after thyroidectomy. Conventional nerve monitoring requires a
      general anesthesia and placement of a special endotracheal tube equipped with
      electrodes to evoke the laryngeal nerves. This study aims to assess feasibility
      and efficacy of a novel technique of neuromonitoring of the EBSLN under local
      anesthesia during minimally invasive thyroidectomy. STUDY DESIGN; PROSPECTIVE
      STUDY: This study is a prospective trial to evaluate the efficacy of nerve
      monitoring of the EBSLN during minimally invasive thyroidectomy under local
      anesthesia. Patient self-assessment of changes in perceived voice severity prior
      to and 3 weeks after surgery was assessed with the Voice Handicap Index-10 (VHI
      10). RESULTS: Thyroidectomy was successfully completed under local anesthesia in
      all cases. The recurrent laryngeal nerve(s) was identified and preserved in each
      patient as demonstrated by normal perioperative transnasal flexible laryngoscopy.
      A total of 15 EBSLNs were at risk, but only 8 EBSLNs (53%) were definitively
      identified. Neuromonitoring demonstrated preservation of the EBSLN in 100% of
      cases. The analysis of the results of the VHI-10 questionnaire before and 3 weeks
      after surgery indicated no significant change in patients' perception of voice
      severity. CONCLUSION: Monitoring of the EBSLN during thyroidectomy under local
      anesthesia is a feasible alternative to conventional nerve monitoring under
      general anesthesia. This technique may be useful for the preservation of voice
      quality during a minimally invasive thyroidectomy under local anesthesia.

PMID- 19160385
TI  - Cochlear implantation is associated with minimal anesthetic risk in the elderly.
AB  - OBJECTIVES/HYPOTHESIS: Most elderly patients with severe to profound hearing loss
      are not being referred for cochlear implantation (CI), the only intervention to
      significantly improve hearing and quality of life in this population. Possible
      concern over the risks of anesthetic in the elderly may be one of the foremost
      concerns. The authors investigated whether advanced age is a risk factor when
      undergoing general anesthesia for cochlear implantation. STUDY DESIGN:
      Retrospective chart review. METHODS: A retrospective chart review was conducted
      at a tertiary academic referral center of 70 patients older than 70 years, who
      underwent CI with general anesthesia between 1984 and 2007, and for whom
      anesthesia records were available. Patients were divided into anesthetic risk
      group A (American Society of Anesthesiologist classification [ASA] I/II) and B
      (ASA III/IV). Intraoperative and postoperative anesthesia-related complications
      were identified. RESULTS: Of the 70 patients, 44 were in group A and 26 were in
      group B, both with a mean age of 77. Four patients, one from group A and three
      from group B, required intraoperative pressors for blood pressure support. There
      were no anesthesia-related complications in group A, but there were three (12% of
      group B and 4% overall) in group B: delayed extubation, postoperative congestive
      heart failure, and urinary retention. There was no long-term morbidity or
      mortality. CONCLUSIONS: General anesthesia is well tolerated by elderly patients
      undergoing cochlear implantation. Preexisting medical condition of the patient as
      defined by ASA is a better predictor of intraoperative and postoperative
      complication than age alone.

PMID- 19160386
TI  - Utility of anti-HSP 70, TNF-alpha, ESR, antinuclear antibody, and
      antiphospholipid antibodies in the diagnosis and treatment of sudden
      sensorineural hearing loss.
AB  - OBJECTIVES: To investigate the performance of various laboratory tests used for
      patients with sudden sensorineural hearing loss (SSNHL). STUDY DESIGN:
      Prospective clinical trial. METHODS: Thirty patients who presented with SSNHL and
      30 healthy people with no cochleovestibular disorders were selected as study and
      control groups. The laboratory panel includes the following tests: anti-HSP 70
      antibody immunoassay, tumor necrosis factor-alpha (TNF-alpha), erythrocyte
      sedimentation rate (ESR), antinuclear antibody (ANA), and antiphospholipid
      antibodies. The study group was given corticosteroid therapy and separated into
      two groups: the corticosteroid responders and the corticosteroid nonresponders.
      In the follow-up, repeat audiograms were evaluated to determine the response to
      treatment. RESULTS: TNF-alpha was found at lower titers in the study group when
      compared with the control group in contrast to other studies. Also, anti-HSP 70
      was not found in high titers in the study group. ANA and ESR were the two
      parameters that were significantly more positive in the study group compared with
      the control group. CONCLUSIONS: Because of the lack of association between a
      positive test and response to corticosteroid treatment, detection of the anti-HSP
      70 antibody, TNF-alpha, ESR, and ANA, at present, do not offer clinically useful
      information in the treatment of SSNHL. Also, because of the lower titers of TNF
      alpha documented in patients with SSNHL, we do not recommend the use of specific
      TNF-alpha inhibitors in SSNHL.

PMID- 19160387
TI  - Roles of vascular endothelial growth factor, Angiopoietin 1, and Angiopoietin 2
      in nasal polyp.
AB  - OBJECTIVES/HYPOTHESIS: To determine the roles of vascular endothelial growth
      factor (VEGF), Angiopoietin (Ang)-1, and Ang-2 in nasal polyps (NPs) by assaying
      expression patterns and evaluating the effects of dexamethasone (DEX) on these
      factors in organ cultured NPs. STUDY DESIGN: Prospective. METHODS: Expression
      patterns of VEGF, Ang-1, and Ang-2 in NPs were compared with those in inferior
      turbinate mucosa samples. Tissue samples were analyzed using the enzyme-linked
      immunosorbent assay (ELISA) and immunofluorescent staining methods. To determine
      the effects of DEX, NP tissues were cultured using an air-liquid interface
      method. Cultures were maintained in the absence or presence of DEX (10 microM or
      100 microM) for 24 hours, and tissue samples analyzed with ELISA. RESULTS: VEGF
      and Ang-1 levels were significantly higher, whereas the Ang-2 level was
      significantly lower in NPs, compared to inferior turbinate mucosa (P < .05). In
      NPs, VEGF and Ang-1 were detected in glandular epithelial, vascular endothelial,
      as well as stromal inflammatory cells, whereas Ang-2 was detected only in stromal
      inflammatory cells. VEGF and Ang-1 levels were significantly lower, while Ang-2
      levels were significantly higher in 100 microM DEX-treated group than nontreated
      group (P < .01). CONCLUSIONS: Imbalance among VEGF, Ang 1, and Ang 2 may be
      important in the angiogenesis of NPs. Moreover, DEX can control the expression of
      these factors in NPs. We suggest that VEGF and Ang-1 act as positive regulatory
      factors, and Ang-2 functions as a negative regulatory factor of angiogenesis in
      NPs.

PMID- 19160388
TI  - Conchal cartilage butterfly graft in primary functional rhinoplasty.
AB  - OBJECTIVE: To validate the use of the conchal cartilage butterfly graft in
      primary functional rhinoplasty and to review our experience using this technique.
      STUDY DESIGN: A retrospective analysis of patients who underwent conchal
      cartilage butterfly graft reconstruction of the nasal valve in primary
      rhinoplasty. METHOD: A retrospective analysis using patient questionnaires was
      performed. Data were collected to determine patient satisfaction about nasal
      breathing and cosmesis after the procedure. RESULTS: Among the patients, 90% (n =
      90) had improved breathing, 88% (n = 88) were satisfied with their postoperative
      cosmesis, and 89% said they would recommend the procedure to a friend who had
      similar preoperative symptoms. CONCLUSION: Conchal cartilage butterfly graft has
      now been shown to be successful in primary functional rhinoplasty, just as it has
      previously been proven effective in secondary rhinoplasty. Although we have had
      success with many techniques for the correction of internal nasal valve collapse,
      we have found the conchal cartilage butterfly graft to be another outstanding
      technique for the appropriately selected patient.

PMID- 19160389
TI  - Persistent allergic rhinitis has a moderate impact on the sense of smell,
      depending on both nasal congestion and inflammation.
AB  - OBJECTIVES/HYPOTHESIS: A degree of smell disturbance has been found in seasonal
      and perennial allergic rhinitis, but alterations in olfaction in patients with
      persistent allergic rhinitis (PER) have not yet been evaluated. The aims of the
      study were to evaluate the impact of PER on the sense of smell, and to
      characterize this impact based on self-reported hyposmia (SRH) and PER severity.
      STUDY DESIGN/METHODS: A prospective controlled study was performed on 49
      consecutive patients with PER. PER patients were subclassified depending on
      severity and the presence of SRH. Olfactory function was evaluated by the
      Barcelona Smell Test-24 (BAST-24) olfactometry for smell detection,
      identification, and forced choice for first and fifth cranial nerve (CN)
      dependent odors in comparison to a group of 60 healthy volunteers. In patients
      with SRH, obstruction was evaluated by peak nasal inspiratory flow (PNIF) and
      acoustic rhinometry; and nasal inflammation was evaluated by nasal nitric oxide
      (nNO). RESULTS: Most patients with PER (67%) presented SRH. Moderate/severe PER
      (84.8%) predominated among patients with SRH, while mild PER (75%) predominated
      among patients without SRH. Smell detection, identification, and forced choice
      tests were significantly worse in PER patients (P < .05) than in healthy controls
      for the odors related to the first and fifth CN. Among subgroups, patients with
      moderate/severe PER and/or with SRH presented a significant reduction in smell
      detection (P < .05) compared to healthy controls. Nasal NO correlated (R: 0.4; P
      < .05) with loss of smell. CONCLUSIONS: Patients with PER have a moderate loss of
      smell (BAST-24) with a higher impairment in those with self-reported hyposmia and
      moderate-to-severe PER. These results suggest that the sense of smell should be
      further investigated in all patients with allergic rhinitis, both in a clinical
      setting and in clinical trials.

PMID- 19160390
TI  - Poor radiotherapy compliance predicts persistent regional disease in advanced
      head/neck cancer.
AB  - OBJECTIVE: To determine if poor compliance to chemoradiation results in an
      increased rate of persistent neck disease. STUDY DESIGN: Retrospective, cohort
      study in an urban, tertiary-care medical center. METHODS: The study included
      patients with N+ stage III/IV squamous cell carcinoma of the upper aerodigestive
      tract treated with curative-intent chemoradiation, who underwent subsequent
      planned neck dissection. Main outcome measure was persistent regional disease
      evidenced by identifiable carcinoma in neck dissection specimens. Variables
      including age, gender, race, primary site, initial T, N staging, imaging results,
      and treatment compliance were assessed and correlated to positive neck dissection
      pathology. RESULTS: Of 40 patients, 18 (45%) had persistent carcinoma in neck
      dissection specimens while 22 (55%) demonstrated complete response in the neck.
      There were 14 patients (35%) who were poorly compliant to radiotherapy (>or=14
      days treatment interruption) and the remaining 26 patients (65%) were considered
      compliant (<14 missed days). Only 23% of compliant patients had positive
      pathology while 79% of noncompliant patients had positive pathology (hazard
      ratio: 9.9). Noncompliance was the only variable that had a statistically
      significant correlation to positive pathology results (P = .002). Multivariate
      logistic regression showed all other variables to be insignificant in predicting
      pathology. CONCLUSIONS: This study found that poorly compliant patients are at
      significantly higher risk of persistent neck disease. Poor compliance may help
      identify patients who will most benefit from neck dissection after
      chemoradiation. This variable was more predictive than pretreatment variables and
      posttreatment CT scan. Further studies investigating patterns of failure after
      chemoradiotherapy in the poorly compliant patient population are warranted.

PMID- 19160391
TI  - Thermal effects of mobile phones on facial nerves and surrounding soft tissue.
AB  - OBJECTIVE: To investigate the possible thermal effects of microwaves from mobile
      phones on facial nerves (FN) and surrounding soft tissue. STUDY DESIGN: A
      prospective study. METHODS: We studied FN conduction rate and compound muscle
      action potentials (CMAP) on 12 rabbits before exposure to radiofrequency
      radiation (RFR) emitted from a mobile phone. Also, the temperature change in the
      soft tissues around the FN was investigated by a four channel Luxtron fiber optic
      system. A mobile phone with 1900 MHz frequency was placed over the ipsilateral
      ear of the rabbit for 25 minutes, and FN and surrounding tissues were exposed to
      a 1.5 watts pulse modulated (217 packets/s) electromagnetic field. During
      exposure to RFR, immediately after turning off the mobile phone, and 25 minutes
      after the exposure temperature change in the surrounding tissue of the FN was
      recorded and compared to preexposure values. Additionally, another recording
      regarding the FN functions was done and the data were compared to preexposure
      values. RESULTS: The average temperature of the surrounding soft tissues was 0.39
      K higher than the preexposure values during the exposure and immediately after
      turning off the mobile phone, and decreased to normal levels 25 minutes after the
      exposure, which was statistically significant. The amplitudes of FN CMAP after
      radiofrequency radiation exposure were significantly smaller than the preexposure
      amplitudes and the amplitudes were normal in the 25 minute measurement.
      CONCLUSION: The RFR emitted from a mobile phone can cause temporary FN
      dysfunction that can be due to temporary temperature increase in the soft tissue
      around the FN.

PMID- 19160392
TI  - MscL of Bacillus subtilis prevents selective release of cytoplasmic proteins in a
      hypotonic environment.
AB  - Bacillus subtilis serves as an excellent model to study protein secretion at a
      proteomic scale. Most of the extracellular proteins are exported from the
      cytoplasm via the secretory (Sec) pathway. Despite extensive studies, the
      secretion mechanisms of about 25% of the extracellular proteins are unknown. This
      suggests that B. subtilis makes use of alternative mechanisms to release proteins
      into its environment. In search for novel pathways, which contribute to
      biogenesis of the B. subtilis exoproteome, we investigated a possible role of the
      large conductance mechanosensitive channel protein MscL. We compared protein
      secretion by MscL deficient and proficient B. subtilis cells. MscL did not
      contribute to secretion under standard growth conditions. Unexpectedly, we
      discovered that under hypo-osmotic shock conditions specific, normally
      cytoplasmic proteins were released by mscL mutant cells. This protein release was
      selective since not all cytoplasmic proteins were equally well released. We
      established that this protein release by mscL mutant cells cannot be attributed
      to cell death or lysis. The presence of MscL, therefore, seems to prevent the
      specific release of cytoplasmic proteins by B. subtilis during hypo-osmotic
      shock. Our unprecedented findings imply that an unidentified system for selective
      release of cytoplasmic proteins is active in B. subtilis.

PMID- 19160393
TI  - Filtering strategies for improving protein identification in high-throughput
      MS/MS studies.
AB  - Despite the recent advances in streamlining high-throughput proteomic pipelines
      using tandem mass spectrometry (MS/MS), reliable identification of peptides and
      proteins on a larger scale has remained a challenging task, still involving a
      considerable degree of user interaction. Recently, a number of papers have
      proposed computational strategies both for distinguishing poor MS/MS spectra
      prior to database search (pre-filtering) as well as for verifying the peptide
      identifications made by the search programs (post-filtering). Both of these
      filtering approaches can be very beneficial to the overall protein identification
      pipeline, since they can remove a substantial part of the time consuming manual
      validation work and convert large sets of MS/MS spectra into more reliable and
      interpretable proteome information. The choice of the filtering method depends
      both on the properties of the data and on the goals of the experiment. This
      review discusses the different pre- and post-filtering strategies available to
      the researchers, together with their relative merits and potential pitfalls. We
      also highlight some additional research topics, such as spectral denoising and
      statistical assessment of the identification results, which aim at further
      improving the coverage and accuracy of high-throughput protein identification
      studies.

PMID- 19160394
TI  - Predictions of peptides' retention times in reversed-phase liquid chromatography
      as a new supportive tool to improve protein identification in proteomics.
AB  - One of the initial steps of proteomic analysis is peptide separation. However,
      little information from RP-HPLC, employed for peptides separation, is utilized in
      proteomics. Meanwhile, prediction of the retention time for a given peptide,
      combined with routine MS/MS data analysis, could help to improve the confidence
      of peptide identifications. Recently, a number of models has been proposed to
      characterize quantitatively the structure of a peptide and to predict its
      gradient RP-HPLC retention at given separation conditions. The chromatographic
      behavior of peptides has usually been related to their amino acid composition.
      However, different values of retention coefficients of the same amino acid in
      different peptides at different neighborhoods were commonly observed. Therefore,
      specific retention coefficients were derived by regression analysis or by
      artificial neural networks (ANNs) with the use of a set of peptides retention. In
      the review, various approaches for peptide elution time prediction in RP-HPLC are
      presented and critically discussed. The contribution of sequence dependent
      parameters (e.g., amphipathicity or peptide sequence) and peptide physicochemical
      descriptors (e.g., hydrophobicity or peptide length) that have been shown to
      affect the peptide retention time in LC are considered and analyzed. The
      predictive capability of the retention time prediction models based on
      quantitative structure-retention relationships (QSRRs) are discussed in details.
      Advantages and limitations of various retention prediction strategies are
      identified. It is concluded that proper processing of chromatographic data by
      statistical learning techniques can result in information of direct use for
      proteomics, which is otherwise wasted.

PMID- 19160395
TI  - Unraveling the S-nitrosoproteome: tools and strategies.
AB  - One of the major tasks to be accomplished in the postgenomic era is the
      characterization of PTMs in proteins. The S-nitrosation of protein thiols is a
      redox-based PTM that modulating enzymatic activity, subcellular localization,
      complex formation, and degradation of proteins, largely contributes to the
      complexity of cellular proteomes. Although the detection of S-nitrosated proteins
      is problematical due to the lability of S-nitrosothiols, with the improvement of
      molecular tools an increasing range of proteins has been shown to undergo S
      nitrosation. We here review recent proteomic approaches for the systematic
      assessment of potential targets for protein S-nitrosation. The development of new
      analytical methods and strategies over the past several years now allows us to
      investigate the nitrosoproteome on a global scale.

PMID- 19160397
TI  - Iatrogenic tracheal rupture in children: A retrospective study.
AB  - OBJECTIVES: Iatrogenic injuries to the trachea are rare, but life-threatening
      complaints. Causes and treatment methods have been described for adults, but
      there is no literature on aetiology and treatment in children. We performed a
      retrospective study to examine the frequency, aetiology, and treatment of
      iatrogenic injuries to the trachea in children and to develop guidelines for
      their treatment and prevention. METHODS: Retrospective study from 2000-2007 at a
      level I trauma centre. All iatrogenic injuries to the trachea between the cricoid
      cartilage and the level of the carina in children (ages 0-16) were included in
      the study. RESULTS: Between 2000 and 2007, 18 tracheal injuries were treated,
      four of them in children (22%). The primary symptom in all cases was emphysema.
      Diagnosis was confirmed using flexible endoscopy. In all cases, the cause of the
      injury was intubation. Two cases of acute injury were treated conservatively by
      bridging the injury with a tube. Two cases were treated surgically by means of
      end-to-end anastomosis. In all cases, healing by first intention occurred. No
      stenoses were observed during follow-up endoscopy. CONCLUSIONS: Acute tracheal
      ruptures in children can be treated conservatively by bridging the rupture with a
      tube. Injuries to the trachea in which the mucosa is damaged or in which other
      complications, such as fistulae, are present must be treated surgically. The
      prognosis for such injuries is good.

PMID- 19160398
TI  - Substernal goiters and sternotomy.
AB  - OBJECTIVE: To determine what factors predispose patients with retrosternal
      goiters to median sternotomy. STUDY DESIGN: Retrospective review. METHODS:
      Analysis of a single surgeon experience with 113 substernal goiters operated upon
      during a 10-year period. RESULTS: 108 goiters were successfully removed through a
      cervical approach. Four patients required sternotomy, and it was concluded that
      one patient who did not receive sternotomy might have been better managed with
      sternotomy. Factors that led to sternotomy were malignancy, involvement of the
      posterior mediastinum, extensive substernal extension, and the presence of an
      ectopic nodule. The latter two were the most important factors. Revision surgery
      and tracheal compression did not influence the need for sternotomy. CONCLUSIONS:
      On the basis of preoperative imaging, it is possible to predict which patients
      with retrosternal goiters are likely to require median sternotomy. These factors
      are malignancy, extension into the posterior mediastinum, substernal extension
      inferior to the level of the aortic arch, and the lack of a solid attachment
      between the cervical and mediastinal components of the thyroid gland. Although
      previously reported, the latter factor has not received sufficient recognition in
      the management of retrosternal goiter.

PMID- 19160396
TI  - A role for lipid droplets in inter-membrane lipid traffic.
AB  - All cells have the capacity to accumulate neutral lipids and package them into
      lipid droplets. Recent proteomic analyses indicate that lipid droplets are not
      simple lipid storage depots, but rather complex organelles that have multiple
      cellular functions. One of these proposed functions is to distribute neutral
      lipids as well as phospholipids to various membrane-bound organelles within the
      cell. Here, we summarize the lipid droplet-associated membrane-trafficking
      proteins and review the evidence that lipid droplets interact with endoplasmic
      reticulum, endosomes, peroxisomes, and mitochondria. Based on this evidence, we
      present a model for how lipid droplets can distribute lipids to specific membrane
      compartments.

PMID- 19160399
TI  - Triological thesis: concurrent endoscopic sinus surgery and cosmetic rhinoplasty:
      rationale, risks, rewards, and reality.
AB  - OBJECTIVES/HYPOTHESIS: To examine the effect of concurrent endoscopic sinus
      surgery (ESS) on the postoperative course of cosmetic rhinoplasty (CR), identify
      any specific contraindications, and to develop more useful treatment regimen in
      patients undergoing concurrent ESS and CR. STUDY DESIGN: Retrospective case
      control study. METHODS: Consecutive patients undergoing CR (performed by the
      principal investigator (PI) in a tertiary care academic practice) at the same
      operative setting as ESS from June 2004-June 2007 were identified. Additionally,
      patients undergoing CR (also by the PI) without ESS over the same time period
      (matched for gender, age, and rhinoplasty approach and techniques) were
      identified and used as control subjects. The office and hospital charts of these
      patients were reviewed for details of pre-, intra-, peri-, and postoperative
      care, preoperative CT scans as well as for patient and physician observations.
      Specifically noted were details regarding the type of cosmetic changes sought,
      course of symptoms of chronic sinusitis, prior treatment, surgical techniques
      used for both ESS and CR, and postoperative treatment with antibiotics and
      corticosteroids. Additionally, a literature review of articles describing
      concurrent CR and ESS was performed. RESULTS: Thirteen patients were identified
      who underwent ESS at the same time as CR. There were no cases of cerebrospinal
      fluid leak, epistaxis, orbital complications, septal perforation, cellulitis or
      saddle nose deformity. No correlation was found between sinus surgery performed
      and need for revision surgery (CR or ESS) or postoperative infections. However,
      the time to patient reported resolution of postoperative nasal swelling was
      significantly higher in patients undergoing concurrent ESS/CR compared to CR only
      (dorsal swelling: 9.62 +/- 6.18 (ESS/CR) vs. 5.85 +/- 1.95 (CR) weeks, P = .0469;
      nasal tip swelling: 19.31 +/- 13.02 (ESS/CR) vs. 10.38 +/- 2.96 (CR) weeks, P =
      .0240, unpaired t test). The same relation held true for doctor noted
      postoperative edema (nasal dorsal edema: 10.62 +/- 7.32 (ESS/CR) vs. 6.31 +/-
      2.72 (CR) weeks, P = .0582; nasal tip edema: 21.46 +/- 15.66 (ESS/CR) vs. 12.23
      +/- 4.10 (CR) weeks, P = .0508, unpaired t test). Among patients who underwent
      concurrent ESS and CR, this time was highly correlated with the severity of sinus
      disease on preoperative CT scanning (r(2) = 0.8573, P < .0001). A greater need
      for postoperative corticosteroid injections in the ESS/CR group was suggestive
      but not statistically significant (30.8% vs. 0%, P = .0957). CONCLUSIONS: While
      our data supports concurrent ESS and CR as safe, our findings suggest that the
      presence and treatment of concurrent sinonasal disease prolongs the patients'
      recovery from CR. This may be due to the effects of sinus pathology and
      manipulation of sinonasal venous and lymphatic drainage patterns or could be due
      to subclinical infectious soiling of rhinoplasty tissue planes. We recommend a
      two-team approach to promote excellent surgical technique, avoid surgeon fatigue,
      and enhance patient care. We recommend adequate medical management of chronic
      sinusitis prior to surgery, pre, intra and postoperative antibiotic coverage,
      appropriate postoperative sinus toilet beginning 1 week after surgery and careful
      and close patient follow-up to optimize results. Most importantly, we advocate
      close coordination of sinonasal and rhinoplastic care in a two-team approach to
      maximize care.

PMID- 19160400
TI  - Air quality influences the prevalence of hay fever and sinusitis.
AB  - OBJECTIVES: Determine associations between air quality and the prevalence of hay
      fever and sinusitis. STUDY DESIGN: Cross-sectional study. METHODS: The National
      Health Interview Survey for the calendar years 1997-2006 adult sample was
      analyzed to determine for each calendar year the one-year period prevalence of
      the two respiratory conditions, hay fever and sinusitis and the nonrespiratory
      (control) condition, weak/failing kidneys. From the Environmental Protection
      Agency, yearly historical data for air quality criteria pollutants, carbon
      monoxide, nitrous dioxide, sulfur dioxide, and particulate matter, were
      tabulated. Graphical and linear regression analyses were conducted for each
      disease condition against each of the air quality variables to determine if
      higher pollutant concentrations predicted a higher prevalence for the disease
      condition. RESULTS: A total of 313,982 patients were studied over the 10 calendar
      years 1997-2006. Mean patient age increased very slightly from year to year
      (overall average, 45.2 years); the percentage of female patients remained the
      same. The air concentrations of each of the criteria pollutants decreased
      steadily over time with the exception of particular matter, which reached a
      plateau in the most recent 3 years. For each of the disease conditions a
      statistically significant relationship with air quality (all p < .001) was
      obtained. For the control condition of kidney failure/weakening, the standardized
      regression coefficient with air quality was very small (range-0.001-0.004). For
      hay fever and sinusitis, substantially larger coefficients were obtained ranging
      from 0.0120-.016 and 0.013-0.027, respectively. CONCLUSIONS: Prevalence of hay
      fever and sinusitis are correlated with air quality. Improvements in air quality
      are associated with decreased prevalence of both hay fever and sinusitis.
      Laryngoscope, 2009.

PMID- 19160401
TI  - Frequency of a dental source for acute maxillary sinusitis.
AB  - OBJECTIVE: To identify radiographic features of odontogenic acute maxillary
      sinusitis and to determine the frequency of a causative dental infection in
      patients with radiographic evidence of maxillary sinus fluid. STUDY DESIGN:
      Retrospective review of 101 sinus computed tomography scans with unilateral or
      bilateral maxillary sinus fluid. METHODS: Each maxillary sinus was graded for
      extent of fluid, degree of mucosal thickening, and presence of dental pathology.
      Univariate chi-square analysis was used to identify potential radiologic and
      demographic features predictive of sinus fluid. Multivariate logistic regression
      was then used to determine which features were independently predictive. RESULTS:
      124 of the 202 maxillary sinuses (61%) had sinus fluid. Univariate analysis
      excluded age, gender, and prior surgery as predictive features. The multivariate
      analysis included the radiographic features of oroantral fistula, periapical
      abscess, periodontal disease, projecting tooth root, and dental caries. Of these,
      only oroantral fistula and the combination of periodontal disease with either a
      projecting tooth root or periapical abscess were identified as significant
      sources of maxillary sinusitis. In sinuses that were <1/3 opacified by fluid, 17%
      had a dental source of infection. In sinuses with 1/3 to 2/3 fluid opacification,
      53% had an identifiable dental source, and in sinuses that were >2/3 opacified by
      fluid, 79% had an identifiable dental source. Mucosal thickening demonstrated a
      similar relationship with dental sources, so that sinuses having both >2/3 fluid
      opacification and moderate mucosal thickening were 86% likely to have an
      identifiable dental source. CONCLUSIONS: Odontogenic infections are often the
      source of acute maxillary sinusitis, especially if the radiographic findings of
      sinusitis are severe.

PMID- 19160402
TI  - Sonography-assisted cutting needle biopsy in the head and neck for the diagnosis
      of lymphoma: can it replace lymph node extirpation?
AB  - OBJECTIVES: Malignant lymphoma frequently present with cervical lymph node
      enlargement. Before adequate therapy can be instituted, appropriate biopsy
      specimens must enable definite subclassification of the disease. While lymph node
      extirpation, traditionally considered the gold standard in the diagnostic
      evaluation of lymphoma, is invasive, diagnoses from fine needle aspiration
      cytology are often clinically insufficient on which to base treatment decisions.
      The aim of this study was to evaluate the diagnostic accuracy of cutting needle
      biopsy (CNB) in the management of patients in whom lymphoma was diagnosed or
      suspected in the head and neck. STUDY DESIGN: Prospective quality assessment
      study in an academic tertiary care medical center. METHODS: A systematic
      clinicopathological follow-up study was performed over a period of 54 months,
      including the results of 347 CNBs in 160 patients with cervico-facial masses.
      Ninety-seven CNBs were done in 45 patients with malignant lymphoma as the final
      or the tentative diagnosis. RESULTS: We experienced 100% success in obtaining
      high-quality tissue cores. The target lymph node was correctly sampled in 41 of
      the 45 patients. Within these 41 patients, no false positive or false negative
      results were recorded. Full subclassification of the disease with prompt
      institution of therapy was possible in 92.3% of the lymphoma patients.
      CONCLUSIONS: CNB proved to be a sufficient alternative to open biopsy with
      excellent diagnostic yield and clinical usefulness. We recommend this procedure
      as the initial diagnostic step in patients with suspected lymphoma, either at
      presentation or at recurrence, and advocate its use in peripheral lymphadenopathy
      of the neck.

PMID- 19160403
TI  - The TRbeta1 is essential in mediating T3 action on Akt pathway in human
      pancreatic insulinoma cells.
AB  - Thyroid hormone action, widely recognized on cell proliferation and metabolism,
      has recently been related to the phosphoinositide 3 kinase (PI3K), an upstream
      regulator of the Akt kinase and the involvement of the thyroid hormone receptor
      beta1 has been hypothesized. The serine-threonine kinase Akt can regulate various
      substrates that drive cell mass proliferation and survival. Its action has also
      been characterized in pancreatic beta-cells. We previously demonstrated that Akt
      activity and its activation in the insulinoma cell line hCM could be considered a
      specific target of the non-genomic action of T3. In this study we analyzed the
      molecular pathways involved in the regulation of cell proliferation, survival,
      size, and protein synthesis by T3 in a stable TRbeta1 interfered insulinoma cell
      line, derived from the hCM, and evidenced a strong regulation of both
      physiological and molecular events by T3 mediated by the thyroid hormone receptor
      beta1. We showed that the thyroid receptor beta1 mediates the T3 regulation of
      the cdk4.cyc D1.p21(CIP1).p27(KIP1) complex formation and activity. In addition
      TRbeta1 is essential for the T3 upregulation of the Akt targets beta-catenin,
      p70S6K, and for the phosphorylation of Bad and mTOR. We demonstrated that the
      beta1 receptor mediates the T3 upregulation of protein synthesis and cell size,
      together with the cell proliferation and survival, playing a crucial role in the
      T3 regulation of the PI3K/Akt pathway.

PMID- 19160404
TI  - The effect of topical amphotericin B on inflammatory markers in patients with
      chronic rhinosinusitis: a multicenter randomized controlled study.
AB  - BACKGROUND: It has been suggested that an exaggerated immune response to fungi is
      crucial in the pathogenesis of chronic rhinosinusitis (CRS). Based on this
      rationale, the use of topical antifungals (amphotericin B) has been advocated.
      Studies on its clinical effectiveness are, however, contradictory. OBJECTIVES: To
      examine the effect of nasal antifungal treatment on secreted mediators in samples
      of nasal lavage fluid from patients with CRS with or without nasal polyps (NP).
      METHODS: Part two of a prospective double-blind, placebo-controlled multicenter
      clinical trial investigating the effect of 13 weeks of treatment with
      amphotericin B or placebo on the levels of pro-inflammatory cytokines, chemokines
      and growth factors (i.e., IL-1beta, IL-1RA, IL-2, IL-2R, IL-3, IL-4, IL-5, IL-6,
      IL-7, IL-8, IL-10, IL-12 (p40/p70 subunits), IL-13, IL-15, IL-17, TNF-alpha, IFN
      alpha, IFN-gamma, G-CSF, GM-CSF, MIP-1alpha, MIP-1beta, IP-10, MIG, eotaxin,
      RANTES, MCP-1, MCP-2, MCP-3, VEGF, EGF, FGF-basic, HGF, Gro-alpha) and albumin
      via a fluorescent enzyme immunoassay in nasal lavage specimens of CRS patients
      with or without NP. RESULTS: Topical amphotericin B had no significant effect on
      the level of any of the tested pro-inflammatory cytokines, chemokines, and growth
      factors in CRS nasal lavage samples. Treatment with placebo, however, increased
      the level of MIP-1alpha and MIP-1beta, which are mediators involved in wound
      healing. CONCLUSIONS: Topical amphotericin B has no significant effect on
      activation markers of nasal inflammatory cells in chronic rhinosinusitis with or
      without nasal polyps.

PMID- 19160405
TI  - Middle ear pressure change as a function of body position.
AB  - OBJECTIVE: To verify and assess immediate middle ear (ME) pressure changes as a
      function of body position. STUDY DESIGN: A prospective clinical trail. PATIENTS
      AND METHODS: Twenty-six adult volunteers having 52 normal, healthy ears had
      tympanometric ME pressures measured in an upright and recumbent positions.
      Recordings were obtained immediately after positioning and after 3 minutes. The
      main outcome measure was the pressure difference between upright and recumbent
      measurements, that is, positional ME pressure change. RESULTS: All ME pressure
      recordings were within (-)100 to (+)55 mmH(2)O. An instant and significant (P <
      .001) pressure elevation was recorded in all ears once position changed from
      upright to recumbent. The average pressure increment was 19 mmH(2)O. Once a
      recumbent ear was repositioned upright it demonstrated an immediate pressure drop
      and regaining the initial ME pressure. Assuming the volume of a normal ME cleft
      as 8 mL and following Boyle's law, an ME volume alteration of about 17 microL was
      required to induce such pressure change. CONCLUSIONS: Positional pressure changes
      were within the range of normal daily ME pressure variations. The instantaneous
      pressure changes and reversibility may be explained by filling and emptying of
      blood vessels within the ME cleft, following gravity causing an alteration of the
      aerated volume. Individual differences of pressure change may follow variability
      of ME cleft volume, its surface, and vessel density.

PMID- 19160406
TI  - Candidate's Thesis: Laryngotracheal separation in neurologically impaired
      children: long-term results.
AB  - OBJECTIVES: Fifty-six consecutive neurologically impaired pediatric children
      underwent laryngotracheal separation (LTS) for acute recurrent and chronic
      aspiration in the last 18 years. The population demographics, indications for
      surgery, and comorbidities are reviewed. This study reports early and late
      complications and survivorship including admissions for pneumonia/aspiration.
      Diagnosis related group (DRGs) and work relative value units (wRVUs) were
      measured to document the potential benefits before and after LTS. STUDY DESIGN:
      Retrospective review of patient charts and records in an electronic medical
      record during an 18 year period. METHODS: Information was obtained by a chart
      review and utilization of the electronic medical record. Patient specific DRG and
      wRVU data on their hospitalizations and outpatient encounters at the Alfred I.
      duPont Hospital for Children of the Nemours Foundation and survival data were
      recorded. Data was analyzed using chi-square analysis, a two-tailed t test, and a
      Fisher's Exact test. RESULTS: Laryngotracheal separation achieved complete
      control of aspiration in all the children. A significant reduction in the number
      of hospital admissions for pneumonias after surgery was noted. After LTS there
      was a reduced average number of DRGs per month (p < .001) as well as wRVUs.
      Transient fistula formation (11%) was the most common complication. No patient
      had his or her procedure reversed to date. CONCLUSION: Laryngotracheal separation
      is 100% effective in controlling aspiration in all of neurologically impaired
      children in this study, It is a valuable procedure to prolong the life of
      children who have intractable aspiration. After LTS, a decrease in DRGs and wRVUs
      reduces health care costs for these patients. Prior to LTS, all medical and
      surgical treatment options for aspiration should be discussed and considered,
      based on the extent of the child's underlying neurologic status, ability to
      verbally communicate, degree of upper airway obstruction, and hope of recovery of
      neurologic function.

PMID- 19160407
TI  - Phonomicrosurgical treatment of intracordal vocal-fold cysts in singers.

PMID- 19160408
TI  - Mitomycin C and the endoscopic treatment of laryngotracheal stenosis: are two
      applications better than one?
AB  - OBJECTIVES/HYPOTHESIS: Endoscopic treatment of laryngotracheal stenosis by airway
      dilation, despite short-term improvement, is often associated with long-term
      relapse. Mitomycin-C (MMC) inhibits fibroblast proliferation and synthesis of
      extracellular matrix proteins, and thereby modulates wound healing and scarring.
      MMC application at the time of endoscopic dilation and laser surgery has been
      suggested to improve outcomes, but this has not been studied in a rigorous
      manner. This study examines the hypothesis that two topical applications of MMC
      given 3-6 weeks apart will result in decreased scarring/restenosis of the airway,
      when compared to a single topical application. STUDY DESIGN: A randomized,
      prospective, double-blind, placebo-controlled clinical trial. METHODS: Twenty-six
      patients with laryngotracheal stenosis due to idiopathic subglottic stenosis,
      postintubation stenosis, or Wegener's granulomatosis entered a protocol to
      receive three endoscopic CO(2) laser and dilation procedures over a 3-month
      interval. At the first procedure, after radial CO(2) laser incision and airway
      dilation, all patients received topical application of MMC (0.5 mg/mL) to the
      airway lesion. One month later, a second endoscopic incision and dilation was
      performed and the patients were randomized to either a second application of
      mitomycin-C or to application of saline placebo. A third dilation procedure was
      performed 2 months later, without MMC application. Patients were followed for up
      to 5 years for relapse of airway stenosis with clinical symptoms sufficient to
      require a subsequent procedure. RESULTS: The relapse rates at 1, 3, and 5 years
      were 7%, 36%, and 69% for patients treated with two applications of MMC compared
      to 33%, 58%, and 70% for patients treated with one application of MMC. The median
      interval to relapse was 3.8 years in the two-application group, compared with 2.4
      years in the one-application group. CONCLUSIONS: This prospective randomized
      double-blind placebo-controlled trial suggests that, in the endoscopic management
      of laryngotracheal stenosis, two applications of MMC given 3-4 weeks apart after
      airway radial incision and dilation reduces the restenosis rate for 2 to 3 years
      after treatment when compared to a single application. However, restenosis and
      delayed symptom recurrence continues so that at 5 years the relapse rates are the
      same. Thus, MMC may postpone, but does not prevent, the recurrence of symptomatic
      stenosis in the majority of patients.

PMID- 19160409
TI  - Differential expression of nuclear matrix proteins during the differentiation of
      human neuroblastoma SK-N-SH cells induced by retinoic acid.
AB  - To investigate the alteration of nuclear matrix proteins (NMPs) during the
      differentiation of neuroblastoma SK-N-SH cells induced by retinoic acid (RA),
      differentiation markers were detected by immunocytochemistry and NMPs were
      selectively extracted and subjected to two-dimensional gel electrophoresis
      analysis. Immunocytochemical observation demonstrated that the expression of
      neuronal markers was up-regulated in SK-N-SH cells following RA treatment.
      Meanwhile, 52 NMPs (41 of which were identified) changed significantly during SK
      N-SH differentiation; four of these NMPs were further confirmed by
      immunoblotting. This study suggests that the differentiation of neuroblastoma
      cells was accompanied by the altered expression of neuronal markers and NMPs. The
      presence of some differentially expressed NMPs was related to the proliferation
      and differentiation of neuroblastomas. Our results may help to reveal the
      relationship between NMPs and neuroblastoma carcinogenesis and reversion, as well
      as elucidate the regulatory principals driving neural cell proliferation and
      differentiation.

PMID- 19160410
TI  - Cellular and functional analysis of four mutations located in the mitochondrial
      ATPase6 gene.
AB  - The smallest rotary motor of living cells, F0F1-ATP synthase, couples proton flow
      generated by the OXPHOS system-from the intermembrane space back to the matrix
      with the conversion of ADP to ATP. While all mutations affecting the multisubunit
      complexes of the OXPHOS system probably impact on the cell's output of ATP, only
      mutations in complex V can be considered to affect this output directly. So far,
      most of the F0F1-ATP synthase variations have been detected in the mitochondrial
      ATPase6 gene. In this study, the four most frequent mutations in the ATPase6
      gene, namely L156R, L217R, L156P, and L217P, are studied for the first time
      together, both in primary cells and in cybrid clones. Arginine ("R") mutations
      were associated with a much more severe phenotype than Proline ("P") mutations,
      in terms of both biochemical activity and growth capacity. Also, a threshold
      effect in both "R" mutations appeared at 50% mutation load. Different mechanisms
      seemed to emerge for the two "R" mutations: the F1 seemed loosely bound to the
      membrane in the L156R mutant, whereas the L217R mutant induced low activity of
      complex V, possibly the result of a reduced rate of proton flow through the A6
      channel.

PMID- 19160411
TI  - The nucleosomal binding protein NSBP1 is highly expressed in the placenta and
      modulates the expression of differentiation markers in placental Rcho-1 cells.
AB  - We report that NSBP1, a nucleosome binding protein that affects the structure of
      chromatin, is highly expressed in mouse placenta. In Rcho-1 cells, which
      recapitulate the differentiation of trophoblast giant cells of living placenta,
      NSBP1 expression is linked to differentiation. Disregulation of NSBP1 protein
      levels, by either siRNA treatment or by overexpression, alters the expression of
      several members of the prolactin gene family without affecting the levels of
      several transcription factors involved in placental differentiation. Our studies
      identify NSBP1 as a nucleosome binding protein that modulates the expression of
      prolactin gene family members most likely by inducing changes in chromatin
      structure.

PMID- 19160412
TI  - Unusual sterolic mixture, and 24-isopropylcholesterol, from the sponge Ciocalypta
      sp. reduce cholesterol uptake and basolateral secretion in Caco-2 cells.
AB  - An unusual sterolic mixture (82.3% of 24-isopropylated sterols) and its major
      component, 24-isopropylcholesterol, isolated from a marine sponge, Ciocalypta sp.
      (Halichondriidae), reduce cholesterol uptake, basolateral secretion and ACAT-2
      mRNA expression and increase the expression of ABCA1 mRNA in Caco-2 cells. The
      decreases of cholesterol uptake and secretion induced by 24-isopropylcholesterol
      alone were more than that of both the sterolic mixture and beta-sitosterol. These
      data add a new sterol, 24-isopropylcholesterol, to sterols that may reduce
      intestinal cholesterol absorption.

PMID- 19160413
TI  - Adenosine triggers the nuclear translocation of protein kinase C epsilon in H9c2
      cardiomyoblasts with the loss of phosphorylation at Ser729.
AB  - Adenosine is a major mediator of ischaemic preconditioning (IPC) and
      cardioprotection. The translocation and activation of protein kinase C epsilon,
      triggered by adenosine, are essential for these processes. We report here that
      H9c2 cardiomyoblasts express five PKC isoforms (alpha, beta(I), delta, epsilon
      and zeta). PKCepsilon is predominantly associated with F-actin fibres in
      unstimulated H9c2 cells but translocates to the nucleus on stimulation with
      adenosine. Cytosolic PKCepsilon associated with F-actin fibres is phosphorylated
      at Ser729 but nuclear PKCepsilon lacks phosphorylation at this site. Adenosine
      triggers the nuclear translocation after 5 min stimulation. PKCepsilon Ser729Ala
      and Ser729Glu mutants showed no translocation on adenosine stimulation suggesting
      both phosphorylation and serine at 729 are critical for this translocation. Among
      five PKC isoforms (alpha, beta(I), delta, epsilon and zeta) detected, PKCepsilon
      is the only isoform translocating to the nucleus upon adenosine stimulation.
      Disruption of microtubules (MTs), but not F-actin-rich fibres, blocked
      translocation of both endogenous PKCepsilon and overexpressed GFP-PKCepsilon to
      the nucleus. Ten proteins interacted with cytosolic PKCepsilon; five of which are
      components of myofibrils. Matrin 3 and vimentin interacted with nuclear
      PKCepsilon. These findings suggest that adenosine stimulates PKCepsilon
      translocation to the nucleus in H9c2 cells in a mechanism involving
      dephosphorylation at Ser729 and MT, which should advance our understanding of the
      signalling pathways stimulated by adenosine in IPC and cardioprotection.

PMID- 19160414
TI  - Identification and expansion of human osteosarcoma-cancer-stem cells by long-term
      3-aminobenzamide treatment.
AB  - A novel cancer stem-like cell line (3AB-OS), expressing a number of pluripotent
      stem cell markers, was irreversibly selected from human osteosarcoma MG-63 cells
      by long-term treatment (100 days) with 3-aminobenzamide (3AB). 3AB-OS cells are a
      heterogeneous and stable cell population composed by three types of fibroblastoid
      cells, spindle-shaped, polygonal-shaped, and rounded-shaped. With respect to MG
      63 cells, 3AB-OS cells are extremely smaller, possess a much greater capacity to
      form spheres, a stronger self-renewal ability and much higher levels of cell
      cycle markers which account for G1-S/G2-M phases progression. Differently from MG
      63 cells, 3AB-OS cells can be reseeded unlimitedly without losing their
      proliferative potential. They show an ATP-binding cassette transporter ABCG2
      dependent phenotype with high drug efflux capacity, and a strong positivity for
      CD133, marker for pluripotent stem cells, which are almost unmeasurable in MG-63
      cells. 3AB-OS cells are much less committed to osteogenic and adipogenic
      differentiation than MG-63 cells and highly express genes required for
      maintaining stem cell state (Oct3/4, hTERT, nucleostemin, Nanog) and for
      inhibiting apoptosis (HIF-1alpha, FLIP-L, Bcl-2, XIAP, IAPs, and survivin). 3AB
      OS may be a novel tumor cell line useful for investigating the mechanisms by
      which stem cells enrichment may be induced in a tumor cell line. The
      identification of a subpopulation of cancer stem cells that drives tumorigenesis
      and chemoresistance in osteosarcoma may lead to prognosis and optimal therapy
      determination. Expression patterns of stem cell markers, especially CD133 and
      ABCG2, may indicate the undifferentiated state of osteosarcoma tumors, and may
      correlate with unfavorable prognosis in the clinical setting.

PMID- 19160415
TI  - Immunomodulatory properties of human periodontal ligament stem cells.
AB  - Tissue engineering utilizing periodontal ligament stem cells (PDLSCs) has
      recently been proposed for the development of new periodontal regenerative
      therapies. Although the use of autologous PDLSC transplantation eliminates the
      potential of a significant host immune response against the donor cells, it is
      often difficult to generate enough PDLSCs from one donor source due to the
      variation of stem cell potential between donors and disease state of each
      patient. In this study, we examined the immunomodulatory properties of PDLSCs as
      candidates for new allogeneic stem cell-based therapies. Human PDLSCs displayed
      cell surface marker characteristics and differentiation potential similar to bone
      marrow stromal stem cells (BMSSCs) and dental pulp stem cells (DPSCs). PDLSCs,
      BMSSCs, and DPSCs inhibited peripheral blood mononuclear cell (PBMNC)
      proliferation stimulated with mitogen or in an allogeneic mixed lymphocyte
      reaction (MLR). Interestingly, gingival fibroblasts (GFs) also suppressed
      allogeneic PBMNC proliferation under both assay conditions. PDLSCs, BMSSCs,
      DPSCs, and GFs exhibited non-cell contact dependent suppression of PBMNC
      proliferation in co-cultures using transwells. Furthermore, conditioned media
      (CM) derived from each cell type pretreated with IFN-gamma partially suppressed
      PBMNC proliferation when compared to CMs without IFN-gamma stimulation. In all of
      these mesenchymal cell types cultured with activated PBMNCs, the expression of
      TGF-beta1, hepatocyte growth factor (HGF) and indoleamine 2, 3-dioxygenase (IDO)
      was upregulated while IDO expression was upregulated following stimulation with
      IFN-gamma. These results suggest that PDLSCs, BMSSCs, DPSCs, and GFs possess
      immunosuppressive properties mediated, in part, by soluble factors, produced by
      activated PBMNCs. J. Cell. Physiol. 219: 667-676, 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19160416
TI  - Thermal killing of human colon cancer cells is associated with the loss of
      eukaryotic initiation factor 5A.
AB  - Heat-induced cell death appears to be a cell-specific event. Chronic heat stress
      was lethal to human colon cancer cells (Caco-2, HT29, and HCT116), but not to
      normal diploid fibroblasts and other cancer cells (BJ-T, WI38, HeLa, ovarian
      2008, WI38VA). Acute heat stress (45-51 degrees C, 30 min) caused cell death of
      colon cancer cells during recovery at physiological temperature. Thermal killing
      of Caco-2 cells was not mediated via oxidative stress since Caco-2 cells were
      much more resistant than HeLa and other cancer cells to H(2)O(2)-induced cell
      death. Acute heat stress caused a striking loss of eukaryotic initiation factor
      5A (eIF5A) in colon cancer cells, but not in HeLa and other normal or transformed
      human fibroblasts. The heat-induced loss of eIF5A is likely to be due to changes
      in the protein stability. The half-life of eIF5A was changed from >20 h to less
      than 30 min during the acute heat stress. Sequence analysis of the eIF5A gene
      from Caco-2 and HeLa cells did not reveal any difference, suggesting that the
      change in stability in Caco-2 cells was not due to any eIF5A mutation.
      Pretreatment of cells with protease inhibitors such as phenylmethyl sulfonyl
      fluoride (PMSF) partially blocked the heat-induced loss of eIF5A and prevented
      heat-induced cell death. In light of the essential role of eIF5A in cell survival
      and proliferation, our results suggest that the stability of eIF5A may have an
      important role in determining the fate of the particular cell type after severe
      heat stress.

PMID- 19160417
TI  - Hypoxia or in situ normoxia: The stem cell paradigm.
AB  - Although O(2) concentrations are considerably lowered in vivo, depending on the
      tissue and cell population in question (some cells need almost anoxic environment
      for their maintenance) the cell and tissue cultures are usually performed at
      atmospheric O(2) concentration (20-21%). As an instructive example, the
      relationship between stem cells and micro-environmental/culture oxygenation has
      been recapitulated. The basic principle of stem cell biology, "the generation-age
      hypothesis," and hypoxic metabolic properties of stem cells are considered in the
      context of the oxygen-dependent evolution of life and its transposition to
      ontogenesis and development. A hypothesis relating the self-renewal with the
      anaerobic and hypoxic metabolic properties of stem cells and the actual O(2)
      availability is elaborated ("oxygen stem cell paradigm"). Many examples
      demonstrated that the cellular response is substantially different at atmospheric
      O(2) concentration when compared to lower O(2) concentrations which better
      approximate the physiologic situation. These lower O(2) concentrations,
      traditionally called "hypoxia" represent, in fact, an in situ normoxia, and
      should be used in experimentation to get an insight of the real cell/cytokine
      physiology. The revision of our knowledge on cell/cytokine physiology, which has
      been acquired ex vivo at non physiological atmospheric (20-21%) O(2)
      concentrations representing a hyperoxic state for most primate cells, has thus
      become imperious.

PMID- 19160418
TI  - Nongenomic effect of estrogen on the MAPK signaling pathway and calcium influx in
      endometrial carcinoma cells.
AB  - 17beta-Estradiol (E2) is well known to interact with intracellular receptors that
      act as nuclear transcription factors. However, abundant evidence now indicates
      that E2 can also rapidly induce several nongenomic effects through signaling
      pathways related to cell growth, preservation, and differentiation. We studied
      the nongenomic effects of E2 in two human endometrial carcinoma cell lines,
      Ishikawa (estrogen receptor (ER) positive) and Hec-1A (ER negative or low) by
      cultivating them with either E2 or its membrane-impermeable conjugate, E2-BSA. We
      found that phosphorylation of Erk1/2 could be induced by either E2 or E2-BSA in
      Ishikawa cells. In Hec-1A cells, only E2 was able to induce Erk1/2
      phosphorylation. Although the existence of a nongenomic component to the response
      was indicated by the finding that it could not be completely inhibited by the ER
      antagonist ICI182780,and it can also be inhibited by calcium inhibitor Nifedipine
      partly. Phosphorylation of Akt could not be induced, either by E2 or E2-BSA, in
      either cell line. Both E2 and E2-BSA elicited calcium influx in Ishikawa cells.
      In contrast to these nongenomic effects, only E2 was able to stimulate expression
      of the anti-apoptotic-protein Bcl-2. Taken together, these data indicate that
      nongenomic effects such as Erk1/2 phosphorylation and calcium influx can be
      initiated from the membrane in Ishikawa cell, and calcium can activate Erk1/2
      phosphorylation. Except for ER, there must be other binding location of estrogen
      in endometrial cancer cells, and the nongenomic effects of estrogen initiated
      from plasma membrane by E2-BSA cannot lead to transcriptional effect of Bcl-2
      expression.

PMID- 19160420
TI  - Expression profiles of SV40-immortalization-associated genes upregulated in
      various human cancers.
AB  - Immortalization is an early and essential step of human carcinogenesis which is
      associated with alterations in gene expression and regulation. Suppression
      subtractive hybridization (SSH) was successfully performed to identify
      immortalization-associated genes upregulated in SV40-immortalized lung
      fibroblasts. We identified 116 known genes which were related to diverse
      functions, with 32.8% relevant for cell cycle or proliferation indicating the
      potential involvement of these genes in immortalization. We chose eight known
      genes located on the overrepresented chromosomes of non-small-cell lung cancers
      (NSCLCs). ASPM, RFC4, C3orf26, BXDC2, C15orf44, AURKA, C20orf77, and RBMX were
      upregulated in immortalized cells, cancer cells, and non-small-cell lung cancer
      (NSCLC) tissues. We additionally cloned two novel genes (CHA-V-97 and CHA-V-165)
      which showed similar upregulated expression patterns in cells and tissues
      examined. Identification and further characterization of these genes may provide
      insights of novel players for immortalization and human carcinogenesis.

PMID- 19160419
TI  - The important role of the apoptotic effects of zinc in the development of
      cancers.
AB  - Zinc is a trace element that is essential for the normal function of cells. It is
      a cofactor for the structure and function of a wide range of cellular proteins
      including enzymes, transcription factors, and structural proteins. Recent studies
      have shown that zinc plays a role in the development of various cancers.
      Unfortunately no established common relationships of zinc with cancer development
      and progression have been identified. Zinc is known to have systemic effects such
      as regulation of the immune system as well as direct cellular effects resulting
      in regulation of gene expression, bioenergetics, metabolic pathways, signal
      transduction and cell invasion. Zinc is also reported to regulate cell
      proliferation and growth. In this review presentation we focus on the effects of
      zinc that are involved in the regulation of apoptosis in malignant cells. We
      selected the apoptotic effects of zinc because zinc is reported to both induce
      apoptosis in some cancers and to protect other cancer cells against apoptosis
      induced by other factors. The effects of zinc in the regulation of apoptosis
      appear to be cell type specific. More importantly the reported effects of zinc on
      cancer cells must be viewed from the perspective of the physiological regulation
      of zinc homeostasis. Thus one must be mindful of the experimental conditions
      under which zinc effects are investigated relative to the physiological and
      pathological conditions of cellular zinc distribution and concentrations that can
      exist in situ.

PMID- 19160421
TI  - The autonomous notch signal pathway is activated by baicalin and baicalein but is
      suppressed by niclosamide in K562 cells.
AB  - The Notch signaling pathway plays important roles in a variety of cellular
      processes. Aberrant transduction of Notch signaling contributes to many diseases
      and cancers in humans. The Notch receptor intracellular domain, the activated
      form of Notch receptor, is extremely difficult to detect in normal cells.
      However, it can activate signaling at very low protein concentration to elicit
      its biological effects. In the present study, a cell based luciferase reporter
      gene assay was established in K562 cells to screen drugs which could modulate the
      endogenous CBF1-dependent Notch signal pathway. Using this system, we found that
      the luciferase activity of CBF1-dependent reporter gene was activated by baicalin
      and baicalein but suppressed by niclosamide in both dose- and time-dependent
      manners. Treatment with these drugs modulated endogenous Notch signaling and
      affected mRNA expression levels of Notch1 receptor and Notch target genes in K562
      cells. Additionally, erythroid differentiation of K562 cells was suppressed by
      baicalin and baicalein yet was promoted by niclosamide. Colony-forming ability in
      soft agar was decreased after treatment with baicalin and baicalein, but was not
      affected in the presence of niclosamide. Thus, modulation of Notch signaling
      after treatment with any of these three drugs may affect tumorigenesis of K562
      cells suggesting that these drugs may have therapeutic potential for those tumors
      associated with Notch signaling. Taken together, this system could be beneficial
      for screening of drugs with potential to treat Notch signal pathway-associated
      diseases.

PMID- 19160422
TI  - Ghrelin inhibits early osteogenic differentiation of C3H10T1/2 cells by
      suppressing Runx2 expression and enhancing PPARgamma and C/EBPalpha expression.
AB  - Ghrelin is a 28-residue peptide identified in the stomach as an endogenous ligand
      of the growth hormone secretagogue receptor that is expressed in a variety of
      peripheral tissues, as well as in the brain. In previous studies, ghrelin has
      been shown to stimulate both adipogenic differentiation from preadipocytes and
      osteogenic differentiation from preosteoblasts or primary osteoblasts. This study
      was undertaken to investigate the direct effect of ghrelin on the lineage
      allocation of mesenchymal stem cells (MSCs). We identified ghrelin receptor mRNA
      in C3H10T1/2 cells, and we found the levels of this mRNA to be attenuated during
      osteogenic differentiation. Treatment of cells with ghrelin resulted in both
      proliferation and inhibition of caspase-3 activity. In addition, ghrelin
      decreased serum deprivation-induced bax protein expression and release of
      cytochrome c from the mitochondria, whereas it increased bcl-2 protein
      expression. Moreover, ghrelin inhibited early osteogenic differentiation, as
      shown by alkaline phosphatase activity and staining, and inhibited osteoblast
      specific genes expression by altering Runx2, PPARgamma, and C/EBPalpha protein
      expression.

PMID- 19160423
TI  - Kaempferol induces apoptosis in two different cell lines via Akt inactivation,
      Bax and SIRT3 activation, and mitochondrial dysfunction.
AB  - Kaempferol (3,4',5,7-tetrahydroxyflavone) is a flavonoid with anti- and pro
      oxidant activity present in various natural sources. Kaempferol has been shown to
      posses anticancer properties through the induction of the apoptotic program. Here
      we report that treatment of the chronic myelogenous leukemia cell line K562 and
      promyelocitic human leukemia U937 with 50 microM kaempferol resulted in an
      increase of the antioxidant enzymes Mn and Cu/Zn superoxide dismutase (SOD).
      Kaempferol treatment induced apoptosis by decreasing the expression of Bcl-2 and
      increasing the expressions of Bax. There were also induction of mitochondrial
      release of cytochrome c into cytosol and significant activation of caspase-3, and
      -9 with PARP cleavage. Kaempferol treatment increased the expression and the
      mitochondria localization of the NAD-dependent deacetylase SIRT3. K562 cells
      stably overexpressing SIRT3 were more sensitive to kaempferol, whereas SIRT3
      silencing did not increase the resistance of K562 cells to kaempferol. Inhibition
      of PI3K and de-phosphorylation of Akt at Ser473 and Thr308 was also observed
      after treating both K562 and U937 cells with kaempferol. In conclusion our study
      shows that the oxidative stress induced by kaempferol in K562 and U937 cell lines
      causes the inactivation of Akt and the activation of the mitochondrial phase of
      the apoptotic program with an increase of Bax and SIRT3, decrease of Bcl-2,
      release of cytochrome c, caspase-3 activation, and cell death.

PMID- 19160424
TI  - Surgical and calcium outcomes in 427 patients treated prospectively in an image
      guided and intraoperative PTH (IOPTH) supplemented protocol for primary
      hyperparathyroidism: outcomes and opportunities.
AB  - Unilateral exploration based upon preoperative imaging has become increasingly
      applied in the management of patients with primary hyperparathyroidism.
      Unilateral surgical exploration purportedly has high rates of disease control,
      limited morbidity, and shortened operative time. Unfortunately, significant
      cohorts of patients with primary hyperparathyroidism are unable to have abnormal
      glands localized on preoperative imaging evaluation. AIM: The aim of our study
      was to evaluate the efficacy of Tc(99m) sestamibi preoperative imaging,
      intraoperative Tc(99m) sestamibi with gamma probe, and intraoperative parathyroid
      hormone (IOPTH) assessment in a large cohort of patients with primary
      hyperparathyroidism. RESULTS: A total of 427 patients were prospectively
      evaluated who were deemed surgical candidates for the treatment of primary
      hyperparathyroidism. Of these patients, 240 (56%) presented with positive Tc(99m)
      sestamibi imaging. Another 105 (25%) presented with equivocal Tc(99m) sestamibi
      imaging. Finally, 82 (19%) presented with negative Tc(99m) sestamibi imaging.
      Intraoperative rapid assessment of parathyroid hormone was performed at the time
      of surgical exploration in all patients with negative and equivocal preoperative
      imaging. All 240 patients with positive preoperative imaging underwent unilateral
      surgical exploration utilizing intraoperative Tc(99m) sestamibi with gamma probe.
      The most common finding in the positive Tc(99m) sestamibi scan group was single
      adenoma in 235 (98%). Normocalcemia was achieved in 233 (97%) of these patients,
      although in 25 (10%) this was normocalcemia with a persistent elevation in
      parathyroid hormone (PTH). The most common surgical finding in the equivocal
      Tc(99m) sestamibi scan group was single adenoma in 85 (81%). Additionally 85
      (81%) of these equivocal patients were able to undergo unilateral exploration
      limited by IOPTH assessment. Normocalcemia was achieved in 101/105 (96%) of
      patients; although, 10 patients were normocalcemic with persistently elevated PTH
      and 2 patients had normocalcemia with low PTH. All patients with negative Tc(99m)
      sestamibi scan underwent bilateral cervical exploration plus IOPTH; 52/82 (63%)
      were found to have a single adenoma which was the most common surgical finding.
      Normocalcemia was achieved in 77/82 (94%) of the negative Tc(99m) sestamibi
      cohort; although 5 patients had normocalcemia with persistently elevated PTH and
      2 had normocalcemia with low PTH. Only 3 (0.7%) overall recurrent laryngeal nerve
      injuries were encountered, and only 1 (0.2%) was permanent. Wound complication
      rates are reported in detail and were low and comparable for all three Tc(99m)
      sestamibi imaging based cohorts. CONCLUSIONS: Tc(99m) sestamibi preoperative
      imaging, intraoperative Tc(99m) sestamibi with gamma probe, IOPTH, and
      combinations of these strategies allow for excellent opportunities for targeted
      excision of pathologic parathyroid tissue with the least dissection necessary
      while achieving excellent long-term calcium control and low rates of
      complication.

PMID- 19160425
TI  - Video rigid laryngeal endoscopy compared to laryngeal mirror examination: an
      assessment of patient comfort and clinical visualization.
AB  - OBJECTIVES: To determine whether there are differences in patient preference and
      extent of laryngeal visualization between video rigid (30 degree endoscope)
      laryngoscopy (VRL) and laryngeal mirror examination (LME). STUDY DESIGN: A
      prospective comparison by patients undergoing laryngeal examination by both VRL
      and LME conducted by two examiners experienced in both mirror and rigid video
      endoscopy. METHODS: Forty-three patients had laryngeal examination by both VRL
      and LME in alternating order. Patients were instructed to observe their exam on a
      monitor screen during the rigid exam. At the conclusioon of both laryngeal
      examinations, patients were asked to rank comfort and level of gagging on a 1 to
      10 scale for both VRL and LME, as well as preference between the two methods and
      whether seeing their laryngeal examination on the video screen was helpful. The
      extent of laryngeal visualization by the clinician was recorded for each
      examination. RESULTS: Patient comfort level was greater with VRL (P < .001) and
      gagging was significantly less with VRL (P < .001) compared to LME. VRL provided
      a more complete examination of the larynx by the clinician (P < .001) compared to
      LME. Patient preference significantly favored VRL (79.1%) compared to LME (18.4%)
      and 2.3% had no preference (P < .001) A total of 83.7% found visualization of
      laryngeal exam on the monitor during the VRL helpful. CONCLUSIONS: VRL is
      superior to LME for most patients based on comfort, extent of laryngeal
      examination by the clinician, and patient preference. The majority of patients
      found visualization of their laryngeal examination during VRL to be helpful.

PMID- 19160426
TI  - CT analysis after distraction osteogenesis in Pierre Robin Sequence.
AB  - OBJECTIVES/HYPOTHESIS: Early mandibular lengthening by distraction osteogenesis
      provides an alternative to traditional methods of airway management in infants
      with Pierre Robin sequence (PRS). Little evidence in the medical literature
      quantitatively demonstrates the changes in skeletal, soft tissue, and
      hypopharyngeal spaces with mandibular distraction. STUDY DESIGN: Prospective
      analysis of a cohort of three patients with PRS. METHODS: We reviewed a series of
      infants with PRS and severe upper airway obstruction who underwent mandibular
      distraction. The infants underwent mandibular lengthening with the same internal,
      unidirectional distraction osteogenesis device. Standardized serial computed
      tomography (CT) scans were obtained according to established protocol. Computed
      tomography data were extracted and analyzed with medical image analysis software
      for mandibulo-maxillary arch harmony, symmetry, hypopharyngeal airway volume,
      geniohyoid distance, distraction osteogenesis bone volume, and mandibular length.
      RESULTS: Mandibulo-maxillary alveolar ridge distances were corrected to 0.5 mm
      after distraction. Clinical examination showed good arch harmony without open
      bite or cross-bite deformities. Mandibular ramus was lengthened by 19.5%; the
      body, 43.4%. After distraction, total mandibular length was increased by 26.2%;
      hypopharyngeal airway volume, 192%; posterior distance from pharyngeal wall to
      tongue base, 198.9%; and geniohyoid distance, 14.1%. CONCLUSIONS: Unidirectional
      internal microdistractors can achieve good mandibulo-maxillary arch harmony.
      Hypopharyngeal airway volume increases substantially, with an even greater
      increase in distance between tongue base and posterior pharyngeal wall. As the
      distal mandibular segment is distracted, the hyoid moves anteriorly, with minor
      increase in geniohyoid relationship. Internal mandibular microdistraction devices
      represent a substantial advance in airway obstruction management in infants with
      micrognathia.

PMID- 19160427
TI  - Radiotherapy in laryngeal carcinoma: can a panel of 13 markers predict response?
AB  - OBJECTIVES/HYPOTHESIS: To find biomarkers associated with response to
      radiotherapy in laryngeal cancer that can be used together with clinical
      parameters to improve outcome prediction. METHODS: In this study, 26 patients
      irradiated for laryngeal carcinomas with a local recurrence within two years
      (cases) and 33 patients without recurrence (controls) were included. All
      pretreatment biopsies were arrayed onto a tissue array. Immunohistochemistry was
      performed for 13 biomarkers that were selected from the literature as potential
      predictors for radioresponse in head and neck (HN) cancer: Bcl-2, Bcl-xL, p16,
      p21, p27, p53, cyclin D1, HIF-1alpha, CA9, COX-2, EGFR, ki-67, and pRB. RESULTS:
      Univariate logistic regression models showed borderline statistically significant
      increased relative risks, with positivity for CA9, COX-2, and p53. Goeman's
      global testing revealed an overall association between outcome and the 13 markers
      together with clinical variables. The most important markers were CA9 and COX-2.
      CONCLUSIONS: In laryngeal carcinoma, hypoxia and COX-2 overexpression provide a
      stronger contribution to an increased risk of local recurrence after radiotherapy
      compared with the well-known candidate markers p53, Bcl-2, and cyclin D1.
      However, no robust expression profile for the prediction of radioresistance was
      found.

PMID- 19160428
TI  - Novel compact laptop-based image-guidance system: preliminary study.
AB  - OBJECTIVES: To describe a novel portable laptop-based image-guidance system and
      its preliminary navigational results. METHODS: An optic-based, specially
      developed navigational system and a life-size endoscopic sinus anatomic model
      were used. The model was submitted to computer tomography (CT), and predefined
      anatomic landmarks were used to test the image-guidance accuracy according to the
      real model. RESULTS: All anatomic landmarks were identified by the image-guidance
      system and all matched with endoscopic or eye views. CONCLUSIONS: This novel
      compact navigation device was shown to be fast and reliable. A larger series,
      involving more models, cadavers, and patients, with the evaluation of multiple
      anatomic points needs to be done before we can reliably determine the overall
      accuracy of this novel device. However, this new system is promising, and in the
      future it can be part of the armamentarium of otolaryngologists' personal
      equipment in order to perform low-cost image-guided surgeries in different places
      with the same equipment.

PMID- 19160429
TI  - Antiestrogen therapy for hereditary hemorrhagic telangiectasia: a double-blind
      placebo-controlled clinical trial.
AB  - OBJECTIVES/HYPOTHESIS: Hereditary hemorrhagic telangiectasia (HHT) is associated
      with recurrent epistaxis in 90% of cases. Good response to hormone treatment has
      been documented, although its use remains controversial. The aim of this study
      was to examine the efficacy of an antiestrogenic agent, Tamoxifen, in the
      treatment of HHT-associated epistaxis. METHODS: Twenty-five patients (11 men, 14
      women; mean age 51 years) with a diagnosis of epistaxis due to HHT were randomly
      assigned to receive treatment with oral tamoxifen 20 mg/d or placebo for 6
      months. Follow-up consisted of physical examination and once-monthly blood tests.
      RESULTS: The groups were similar in age and sex distribution. Of the 21
      participants who completed the trial, alleviation of the epistaxis was noted in 9
      of 10 tamoxifen-treated patients and 3 of 11 placebo-treated patients (including
      2 with only temporary improvement). The difference between the groups at the
      trial end point was significant for both frequency (P = .01) and severity (P =
      .049) of the disease. Hemoglobin concentration rose in 4 tamoxifen-treated
      patients and decreased in 5 controls. CONCLUSIONS: Tamoxifen appears to be an
      effective agent for the treatment of epistaxis due to HHT.

PMID- 19160430
TI  - Acute vocal fold hemorrhage caught on video during office exam.
AB  - This article presents a unique video of a laryngeal exam during which a vocal
      fold hemorrhage occurs. This patient had likely been suffering from intermittent
      vocal fold hemorrhages for the last decade due to a persistent vascular lesion
      and an underlying chronic cough.

PMID- 19160431
TI  - Changing patterns of tracheotomy use in anterior skull base surgery with free
      tissue reconstruction.
AB  - OBJECTIVE: To evaluate how changing patterns of tracheotomy use with free tissue
      reconstruction of the anterior skull base affect postoperative complications.
      DESIGN: Retrospective comparison of clinical cohort to historic control group.
      SETTING: Tertiary care medical center. PATIENTS: We reviewed 201 patients with a
      diagnosis of malignant or locally aggressive benign neoplasms of the nasal cavity
      and paranasal sinuses between January 1993 and December 2006. Of these, we
      studied 33 consecutive patients that underwent ablative anterior skull base
      surgery reconstructed with free tissue transfers. We divided the study group into
      two cohorts: Group 1, patients treated from 1993-2000, and Group 2, patients
      treated from 2000-2006. MAIN OUTCOME MEASURES: Tracheotomy use and postoperative
      complications. RESULTS: There were 16 patients in Group 1 and 17 patients in
      Group 2. There were 11 patients who received a tracheotomy in Group 1, and only 5
      in Group 2 (P = .038). Five patients in either group experienced complications (P
      = 1.000). There was one case of meningitis in Group 1 and no cases in Group 2 (P
      = .485). There were two cases of pneumocephalus in Group 2 and none in Group 1 (P
      = .485) and no cases of tension pneumocephalus. Six patients in each group had
      recurrent disease (P = 1.000). There was no statistically significant difference
      in survival (P = .675). CONCLUSIONS: The decreased use of tracheotomy in patients
      undergoing free tissue transfer reconstruction of anterior skull base defects did
      not lead to an increase in complications. Routine use of tracheotomy in these
      patients is unnecessary and should be reserved for selected cases. Laryngoscope,
      2009.

PMID- 19160432
TI  - Outcome of minimally invasive management of salivary calculi in 4,691 patients.
AB  - OBJECTIVE: To evaluate the application of minimally invasive techniques in the
      management of salivary stones. BACKGROUND: The incidence of salivary calculi is
      60 cases/million/year, with most stones situated in the mid or proximal duct. The
      current treatment of these stones is adenectomy. This paper reports the results
      of minimally invasive methods of stone removal that avoid gland excision.
      METHODS: Observational study of 5,528 consecutive patients treated by
      lithotripsy, endoscopy, basket retrieval, and /or surgery in five centers from
      1990 to 2004 inclusive. A total of 567 cases were excluded, leaving 4,691
      patients (parotid n = 1,165, submandibular n = 3,526) for analysis. RESULTS:
      Salivary calculi were eliminated in 3,775/4,691 (80.5%) of cases and partly
      cleared in 782/4,691 (16.7%). Salivary glands were removed in 134/4,691 (2.9%) of
      patients with symptoms in whom treatment failed. CONCLUSIONS: Minimally invasive
      techniques move treatment of salivary calculi to an outpatient or a day case
      setting. They are reliable ways of both retrieving stones and eliminating
      symptoms, and mean that the gland rarely has to be removed.

PMID- 19160433
TI  - Desorption electrospray ionization mass spectrometry of DNA nucleobases:
      implications for a liquid film model.
AB  - Desorption electrospray ionization (DESI) mass spectrometry has been implemented
      on a commercial ion-trap mass spectrometer and used to optimize mass
      spectrometric conditions for DNA nucleobases: adenine, cytosine, thymine, and
      guanine. Experimental parameters including spray voltage, distance between mass
      spectrometer inlet and the sampled spot, and nebulizing gas inlet pressure were
      optimized. Cluster ions including some magic number clusters of nucleobases were
      observed for the first time using DESI mass spectrometry. The formation of the
      cluster species was found to vary with the nucleobases, acidification of the
      spray solvent, and the deposited sample amount. All the experimental results can
      be explained well using a liquid film model based on the two-step droplet pick-up
      mechanism. It is further suggested that solubility of the analytes in the spray
      solvent is an important factor to consider for their studies by using DESI.

PMID- 19160435
TI  - Use of tetradentate monoanionic ligands for stabilizing reactive metal complexes.
AB  - Ligand scaffolding: The chemist's ability to choose from a wide range of
      supporting ligands is an important factor in designing new metal complexes. The
      introduction of new ligand scaffolds with different donor types and coordination
      numbers allows for the expansion of reaction chemistry at metal centers. This
      article surveys the use of the tetradentate monoanionic (TMDA) ligands (shown
      here) with main-group, transition-metal, and f-block elements. Supporting ligand
      design has played a vital role in the development of coordination and
      organometallic chemistry. A myriad of ligands with varying charge, donor-type,
      and denticity have been explored in this realm. A ligand type that has garnered
      recent attention involves a tetradentate monoanionic (TDMA) framework. TDMA
      ligands have been used with p-, d-, and f-block elements to form an array of
      interesting new complexes with applications ranging from bioinorganic chemistry
      to catalysis. Complexes incorporating TDMA ligands have been shown to stabilize
      reactive low-valent and cationic species. Functionalized beta-diiminato and TACN
      derivatives as well as tripodal ligands featuring both hard sigma-donors as well
      as "mixed-donors" are covered in this review. The synthetic challenges associated
      with the implementation of each ligand set are discussed.

PMID- 19160434
TI  - Correct identification of oxidized histidine residues using electron-transfer
      dissociation.
AB  - Oxidative modification to the side chain of histidine can noticeably change the
      collision-induced dissociation (CID) pathways of peptides containing this
      oxidized residue. In cases where an oxidized peptide consists two or more isomers
      differing only in the site of modification, oxidation to histidine usually causes
      the other oxidized sites to be mis-assigned in CID spectra. These spectral
      misassignments can sometimes be avoided by using multiple stages of MS/MS (MS(n))
      or via specially optimized liquid chromatographic separation conditions. In this
      manuscript, we demonstrate that these misassignments can be more readily and
      easily avoided by using electron-transfer dissociation (ETD) to dissociate the
      oxidized peptides. Furthermore, we find that the relative insensitivity of ETD to
      side-chain chemistry allows the extent of oxidative modification to be determined
      readily for peptide isomers having more than one site of oxidation. The current
      results along with previous studies of oxidized peptides suggest that ETD is
      probably a better technique than CID for obtaining correct sequence and
      modification information for oxidized peptides.

PMID- 19160436
TI  - Towards allosteric receptors: adjustment of the rotation barrier of 2,2'
      bipyridine derivatives.
AB  - What a difference! The energy differences between anti and syn conformers as well
      as the energy barrier for the rotation around the aryl-aryl bond of a number of
      2,2'-bipyridine molecules were examined by quantum-chemical methods. The energy
      differences were found to be governed by the substituents directly attached to
      the bipyridine and their ability to form intramolecular hydrogen bonds.Quantum
      chemical calculations at the BP86/TZVP level of theory were performed to
      determine the energy differences between the syn and the anti conformers, as well
      as the energy barrier for the rotation of the aryl-aryl bond of 2,2'-bipyridine
      molecules and a number of disubstituted derivatives. Substitutents with hydrogen
      bond donor (or electron acceptor) functions or hydrogen-bond acceptors (or
      electron donors) are generally found to have large effects on the difference and
      the barrier. Substitution with a hydrogen-bond donor (or an electron acceptor) at
      position 6 and 6' leads to a decrease owing to a charge transfer from the
      pyridine nitrogen lone pair to the donor, which is caused by the formation of
      weak intramolecular hydrogen bonds and/or dipolar interactions, respectively.
      Conversely, substitution at position 4 and 4' causes an increase in the energy
      barrier. Substitution with a hydrogen-bond acceptor (or an electron donor) shows
      the opposite behavior, which can be explained by the weak intramolecular
      interactions. Interestingly, even very weak CH hydrogen-bond donors (electron
      acceptors) such as methyl groups have a significant influence. This indicates the
      importance of such weak interactions for the structure and energetics of
      supramolecular systems. The energy differences are mainly governed by the
      substituents directly attached to the bipyridine core as the introduction of
      sterically demanding groups in the periphery hardly influences the barriers or
      energy differences of the conformers. These findings are important for the design
      of heterotropic positive cooperative allosteric receptors with 2,2'-bipyridines
      as the allosteric centre.

PMID- 19160438
TI  - Ti-catalyzed Barbier-type allylations and related reactions.
AB  - Titanocene(III) complexes, easily generated in situ from commercial Ti(IV)
      precursors, catalyze Barbier-type allylations, intramolecular crotylations
      (cyclizations), and prenylations of a wide range of aldehydes and ketones. The
      reaction displays surprising and unprecedented mechanistic subtleties. In
      cyclizations a fast and irreversible addition of an allyl radical to a Ti(III)
      coordinated carbonyl group seems to occur. Intermolecular additions to conjugated
      aldehydes proceed through a coupling of a Ti(IV)-bound ketyl radical with an
      allyl radical. Reactions of ketones with allylic halides take place by the
      classical addition of an allylic organometallic reagent. The radical coupling
      processes enable transformations such as the highly regioselective alpha
      prenylation that are otherwise difficult to achieve. The mild reaction conditions
      and the possibility to employ titanocene complexes in only catalytic quantities
      are highly attractive features of our protocol. These unusual properties have
      been taken advantage of for the straightforward synthesis of the natural products
      rosiridol, shikalkin, and 12-hydroxysqualene.

PMID- 19160437
TI  - Lactide polymerisation with air-stable and highly active zinc complexes with
      guanidine-pyridine hybrid ligands.
AB  - The synthesis of zinc complexes of guanidine-pyridine hybrid ligands
      [Zn(DMEGpy)Cl(2)] (C1), [Zn(TMGpy)Cl(2)] (C2), [Zn(DMEGqu)Cl(2)] (C3),
      [Zn(TMGqu)Cl(2)] (C4), [Zn(DMEGpy)(CH(3)COO)(2)] (C5), [Zn(TMGpy)(CH(3)COO)(2)]
      (C6), [Zn(DMEGqu)(CH(3)COO)(2)] (C7), [Zn(TMGqu)(CH(3)COO)(2)] (C8),
      [Zn(DMEGqu)(2)(CF(3)SO(3))][CF(3)SO(3)] (C9) and
      [Zn(TMGqu)(2)(CF(3)SO(3))][CF(3)SO(3)] (C10) is reported. These zinc complexes
      were completely characterised and screened regarding their activity in the ring
      opening polymerisation of D,L-lactide. They proved to be active initiators in
      lactide bulk polymerisation, and polylactides with molecular weights (M(w)) up to
      176,000 g mol(-1) could be obtained. They combine high activity with robustness
      towards moisture and air. The influence of reaction temperature and of the
      anionic component of the zinc salt on the activity of the catalyst, as well as
      the occurrence of undesired side reactions, was investigated. By correlating
      these findings with the structural study on the zinc complexes we could deduce a
      structure-reactivity relationship for the zinc catalysts. This study was
      accompanied by DFT calculations. The bis-chelate triflate complexes C9 and C10,
      supported by quinoline-guanidine ligands L3 and L4, exhibit by far the highest
      reactivity. Systematic comparison of these complexes with their mono-chelate
      counterparts and their bis-guanidine analogues allows the attributes that promote
      polymerisation by neutral guanidine ligand systems to be elucidated:
      accessibility to the zinc centre and Lewis acidity.

PMID- 19160439
TI  - Oxidant-free dehydrogenation of alcohols heterogeneously catalyzed by cooperation
      of silver clusters and acid-base sites on alumina.
AB  - A gamma-alumina-supported silver cluster catalyst--Ag/Al(2)O(3)--has been shown
      to act as an efficient heterogeneous catalyst for oxidant-free alcohol
      dehydrogenation to carbonyl compounds at 373 K. The catalyst shows higher
      activity than conventional heterogeneous catalysts based on platinum group metals
      (PGMs) and can be recycled. A systematic study on the influence of the particle
      size and oxidation state of silver species, combined with characterization by Ag
      K-edge XAFS (X-ray absorption fine structure) has established that silver
      clusters of sizes below 1 nm are responsible for the higher specific rate. The
      reaction mechanism has been investigated by kinetic studies (Hammett correlation,
      kinetic isotope effect) and by in situ FTIR (kinetic isotope effect for hydride
      elimination reaction from surface alkoxide species), and the following mechanism
      is proposed: 1) reaction between the alcohol and a basic OH group on the alumina
      to yield alkoxide on alumina and an adsorbed water molecule, 2) C-H activation of
      the alkoxide species by the silver cluster to form a silver hydride species and a
      carbonyl compound, and 3) H(2) desorption promoted by an acid site in the
      alumina. The proposed mechanism provides fundamental reasons for the higher
      activities of silver clusters on acid-base bifunctional support (Al(2)O(3)) than
      on basic (MgO and CeO(2)) and acidic to neutral (SiO(2)) ones. This example
      demonstrates that catalysts analogous to those based on of platinum group metals
      can be designed with use of a less expensive d(10) element--silver--through
      optimization of metal particle size and the acid-base natures of inorganic
      supports.

PMID- 19160440
TI  - Nonglycosidic agonists of invariant NKT cells for use as vaccine adjuvants.
AB  - Based on the crystal structures of human alpha-GalCer-CD1d and iNKT-alpha-GalCer
      CD1d complexes, nonglycosidic analogues of alpha-GalCer were synthesized. They
      activate iNKT cells resulting in dendritic cell maturation and the priming of
      antigen-specific T and B cells. Therefore, they are attractive adjuvants in
      vaccination strategies for cancer and infectious diseases.

PMID- 19160442
TI  - Characterization of dendritic spines in the Drosophila central nervous system.
AB  - Dendritic spines are a characteristic feature of a number of neurons in the
      vertebrate nervous system and have been implicated in processes that include
      learning and memory. In spite of this, there has been no comprehensive analysis
      of the presence of spines in a classical genetic system, such as Drosophila, so
      far. Here, we demonstrate that a subset of processes along the dendrites of
      visual system interneurons in the adult fly central nervous system, called LPTCs,
      closely resemble vertebrate spines, based on a number of criteria. First, the
      morphology, size, and density of these processes are very similar to those of
      vertebrate spines. Second, they are enriched in actin and devoid of tubulin.
      Third, they are sites of synaptic connections based on confocal and electron
      microscopy. Importantly, they represent a preferential site of localization of an
      acetylcholine receptor subunit, suggesting that they are sites of excitatory
      synaptic input. Finally, their number is modulated by the level of the small
      GTPase dRac1. Our results provide a basis to dissect the genetics of dendritic
      spine formation and maintenance and the functional role of spines.

PMID- 19160441
TI  - Biowaiver monographs for immediate release solid oral dosage forms: rifampicin.
AB  - Literature data relevant to the decision to allow a waiver of in vivo
      bioequivalence (BE) testing for the approval of new multisource and reformulated
      immediate release (IR) solid oral dosage forms containing rifampicin as the only
      Active Pharmaceutical Ingredient (API) are reviewed. Rifampicin's solubility and
      permeability, its therapeutic use and index, pharmacokinetics, excipient
      interactions and reported BE/bioavailability (BA) problems were taken into
      consideration. Solubility and absolute BA data indicate that rifampicin is a BCS
      Class II drug. Of special concern for biowaiving is that many reports of failure
      of IR solid oral dosage forms of rifampicin to meet BE have been published and
      the reasons for these failures are yet insufficiently understood. Moreover, no
      reports were identified in which in vitro dissolution was shown to be predictive
      of nonequivalence among products. Therefore, a biowaiver based approval of
      rifampicin containing IR solid oral dosage forms cannot be recommended for either
      new multisource drug products or for major scale-up and postapproval changes
      (variations) to existing drug products.

PMID- 19160443
TI  - Drosophila RSK negatively regulates bouton number at the neuromuscular junction.
AB  - Ribosomal S6 kinases (RSKs) are growth factor-regulated serine-threonine kinases
      participating in the RAS-ERK signaling pathway. RSKs have been implicated in
      memory formation in mammals and flies. To characterize the function of RSK at the
      synapse level, we investigated the effect of mutations in the rsk gene on the
      neuromuscular junction (NMJ) in Drosophila larvae. Immunostaining revealed
      transgenic expressed RSK in presynaptic regions. In mutants with a full deletion
      or an N-terminal partial deletion of rsk, an increased bouton number was found.
      Restoring the wild-type rsk function in the null mutant with a genomic rescue
      construct reverted the synaptic phenotype, and overexpression of the rsk-cDNA in
      motoneurons reduced bouton numbers. Based on previous observations that RSK
      interacts with the Drosophila ERK homologue Rolled, genetic epistasis experiments
      were performed with loss- and gain-of-function mutations in Rolled. These
      experiments provided evidence that RSK mediates its negative effect on bouton
      formation at the Drosophila NMJ by inhibition of ERK signaling.

PMID- 19160444
TI  - Feasibility of complex coronary intervention in combination with percutaneous
      aortic valve implantation in patients with aortic stenosis using percutaneous
      left ventricular assist device (TandemHeart).
AB  - Coronary atherosclerosis is a common finding in patients with severe aortic
      stenosis. Indeed, aortic stenosis is associated with risk factors similar those
      of coronary atherosclerosis such as older age, hypertension, diabetes,
      hypercholesterolemia and smoking. In light of the evolution of percutaneous
      aortic valve implantation (PAVI) and ongoing improvements in techniques of PCI, a
      combined approach using PCI and PAVI can be proposed for patients with complex
      coronary artery and aortic valve disease. This report describes the feasibility
      of the combination of percutaneous coronary intervention and percutaneous aortic
      valve implantation with peripheral left ventricular assist device (TandemHeart)
      support in 3 elderly patients with complex coronary artery disease and aortic
      stenosis considered too high risk for conventional surgical therapy.

PMID- 19160445
TI  - Homozygosity mapping through whole genome analysis identifies a COL18A1 mutation
      in an Indian family presenting with an autosomal recessive neurological disorder.
AB  - The use of genome wide genotyping arrays has the potential to assess entire
      groups of genetic disorders in one application and has begun to emerge as an aid
      to diagnosis in clinical practice. Recessive families may suffer from diseases
      because of homozygosity of recessive alleles; homozygosity tracks can be easily
      identified by using these high throughput SNPs arrays, allowing the rapid mapping
      of autozygous segments that may be associated with the disease. According to
      this, we performed homozygosity mapping using genome wide SNP arrays in a North
      Indian family with an autosomal recessive disorder of ataxia, epilepsy, cognitive
      decline and visual problems. In this kindred, a large number of homozygous
      regions were identified. In silico analysis was also carried out. The COL18A1
      gene found in one of the homozygous tracks has genetic defects previously
      reported with a similar phenotype as our family. Hence, it was the most likely
      candidate gene and at large the first to be analyzed. A homozygous COL18A1 two
      base pair deletio segregating with the disease was identified; expanding the
      spectrum of disease seen in COL18A1 and proving that the genetic lesion
      underlying recessive disorders can rapidly identify by employing genotyping
      arrays along with detailed candidate gene analysis.

PMID- 19160446
TI  - P2RX7: A bipolar and unipolar disorder candidate susceptibility gene?
AB  - The chromosomal region 12q24 has been previously implicated by linkage studies of
      both bipolar disorder and unipolar mood disorder and we have reported two
      pedigrees segregating both bipolar disorder and Darier's disease that show
      linkage across this region. The gene P2RX7 is located in this chromosomal region
      and has been recently reported as a susceptibility gene for bipolar disorder and
      unipolar depression. The non-synonymous SNP rs2230912 (resulting in amino-acid
      polymorphism Q460R) showed the strongest association and has been postulated to
      be pathogenically relevant. We have investigated this gene in a large UK case
      control sample (bipolar I disorder N = 687, unipolar recurrent major depression N
      = 1,036, controls N = 1,204). Neither rs2230912 nor any of 8 other SNPs genotyped
      across P2RX7 was found to be associated with mood disorder in general, nor
      specifically with bipolar or unipolar disorder. Further, sequencing of our two
      chromosome 12-linked bipolar-Darier families showed no evidence of rare variants
      at P2RX7 that could explain the linkage. Our data do not provide support for
      rs2230912 or the other polymorphisms studied within the P2RX7 locus, being
      involved in susceptibility to mood disorders.

PMID- 19160449
TI  - Management of familial hypertriglyceridemia during pregnancy with plasma
      exchange.
AB  - Hypertriglyceridemia-induced pancreatitis is a serious complication of familial
      dyslipidemias. Hormonal influences during pregnancy can compromise otherwise
      controlled lipid levels in women with familial hypertriglyceridemia and
      predispose to pancreatitis leading to increased morbidity in both mother and
      fetus. We report the successful use of therapeutic plasma exchange (TPE) in the
      management of hypertriglyceridemia during pregnancy resulting in avoidance of
      pancreatitis and delivery of a healthy term infant. Thirteen TPEs were performed
      from 19 to 36 weeks gestation to maintain tight control of triglyceride levels.

PMID- 19160450
TI  - Ion/molecule reactions in SiH4/H2S and GeH4/H2S mixtures.
AB  - The gas phase ion chemistry of silane/hydrogen sulfide and germane/hydrogen
      sulfide mixtures was studied by ion trap mass spectrometry (ITMS), in both
      positive and negative ionization mode. In positive ionization, formation of X/S
      (X = Si, Ge) mixed ions mainly takes place via reactions of silane or germane
      ions with H(2)S, through condensation followed by dehydrogenation. This is
      particularly evident in the system with silane. On the other side, reactions of
      H(n)S(2)(+) ions with XH(4) (X = Si, Ge) invariably lead to formation of a single
      X-S bond. In negative ionization, a more limited number of mixed ion species is
      detected, but their overall abundance reaches appreciable values, especially in
      the SiH(4)/H(2)S system. Present results clearly indicate that ion processes play
      an important role in formation and growth of clusters eventually leading to
      deposition of amorphous solids in chemical vapor deposition (CVD) processes.

PMID- 19160451
TI  - Fast and sensitive liquid chromatography/electrospray mass spectrometry method to
      study ocular penetration of EDL-155, a novel antitumor agent for retinoblastoma
      in rats.
AB  - Our group has used the tetrahydroisoquinoline derivative EDL-155 to treat
      glioblastoma in animal models and it is currently being evaluated in the
      treatment of ocular cancers. The purpose of this study was to develop a rapid and
      sensitive liquid chromatography and tandem mass spectrometry (LC-MS/MS) method to
      study the plasma and vitreous humor disposition of EDL-155 in rats. Animals
      received a single periocular injection of EDL-155 (20 mg/kg). Animals were
      sacrificed at specified times (5, 60, 120, 240 and 360 min) and plasma and
      vitreous humor samples were obtained. EDL-155 was isolated by protein
      precipitation and the extracts were analyzed by reversed-phase high-pressure
      liquid chromatography (HPLC) with MS/MS detection. A structurally similar analog
      was used as internal standard (IS). The chromatographic run time was 3.5 min per
      injection. The mass spectrometer was operated in positive-ion, multiple reaction
      monitoring (MRM) mode. The mass transitions monitored were m/z332.2 --> 167.2
      (EDL-155) and m/z391.2 --> 200.2 (IS). The lower limit of quantification (LLOQ)
      was 0.1 ng/ml in both vitreous humor and plasma. The method was validated for
      selectivity, linearity, accuracy and precision in rat vitreous humor and
      partially validated for accuracy and precision in rat plasma. The ion
      suppression, recovery and stability of the analyte in the biological matrix were
      also tested. The assay was rapid, sensitive and robust enough to support EDL-155
      ocular penetration studies in a rodent model of intraocular cancer. Application
      of this method revealed that EDL-155 was rapidly passed into the vitreous humor
      following periocular administration. Further, vitreous humor exposure exceeded
      systemic exposure by approximately sevenfold. High local concentrations coupled
      with minimal systemic exposure supports further testing of EDL-155 as localized
      therapy for intraocular cancers.

PMID- 19160452
TI  - A small high-irradiance laser ionization time-of-flight mass spectrometer.
AB  - A small high-irradiance laser ionization time-of-flight mass spectrometer (LI
      TOFMS) with orthogonal sample introduction was described. High irradiance of 6 x
      10(10) W/cm(2) at 532 nm from a Nd:YAG laser was applied in the experiment to get
      a high ionization degree in plasma and to dissociate the interferential
      polyatomic ions. Meanwhile, the interferential multiply charged ions resulted by
      high-irradiance were nearly eliminated in the spectrum by utilizing helium as the
      buffer gas in the ion source due to three-body recombination, which resulted in a
      relatively clean background. Improved signal stability was obtained by automated
      step moving of the sample stage in short time intervals. By using two sets of
      Einzel lens in transport system, nearly uniform relative sensitivity coefficients
      (RSCs) were achieved for most of metal elements including light ions which were
      detected in extremely low sensitivity in previous hexapole transportation
      instrument. The resolving power reaches 2200, and the detection limits (DLs) are
      10(-6) g/g for metal elements in the steel standard.

PMID- 19160447
TI  - Family-based association of YWHAH in psychotic bipolar disorder.
AB  - YWHAH is a positional and functional candidate gene for both schizophrenia and
      bipolar disorder (BP). This gene has been previously shown to be associated with
      both disorders, and the chromosome location (22q12.3) has been repeatedly
      implicated in linkage studies for these disorders. It codes for the eta subtype
      of the 14-3-3 protein family, is expressed mainly in brain, and is involved in
      HPA axis regulation. We investigated the association of YWHAH with BP in a large
      sample, consisting of 1211 subjects from 318 nuclear families including 554
      affected offspring. We tested for association with the standard BP phenotype as
      well as subtypes defined by psychotic and mood-incongruent features. We genotyped
      five tag SNPs and the (GCCTGCA)(n) polymorphic locus present in this gene. Using
      a family-based association test, we found that rs2246704 was associated with BP
      (OR 1.31, P = 0.03) and psychotic BP (OR = 1.66, P = 0.002). The polymorphic
      repeat and two other SNPs were also modestly associated with psychotic BP. We
      have provided additional evidence for association of variants in YWHAH with major
      mental illness. Additional association analyses of larger sample sets will be
      required to clarify the role of YWHAH in schizophrenia and BP. The use of
      clinical sub-phenotypes such as psychotic features or other potential
      schizophrenia/BP overlap variables including cognitive abnormalities and poor
      functioning might shed further light on the potential subtypes of illness most
      closely associated with genetic variation in YWHAH.

PMID- 19160453
TI  - Effects of the S288c genetic background and common auxotrophic markers on
      mitochondrial DNA function in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae is a valuable model organism for the study of eukaryotic
      processes. Throughout its development as a research tool, several strain
      backgrounds have been utilized and different combinations of auxotrophic marker
      genes have been introduced into them, creating a useful but non-homogeneous set
      of strains. The ade2 allele was used as an auxotrophic marker, and for 'red
      white' screening for respiratory competence. his3 alleles that influence the
      expression of MRM1 have been used as selectable markers, and the MIP1[S] allele,
      found in the commonly used S228c strain, is associated with mitochondrial DNA
      defects. The focus of the current work was to examine the effects of these
      alleles, singly and in combination, on the maintenance of mitochondrial function.
      The combination of the ade2 and MIP1[S] alleles is associated with a slight
      increase in point mutations in mitochondrial DNA. The deletion in the
      his3Delta200 allele, which removes the promoter for MRM1, is associated with loss
      of respiratory competence at 37 degrees C in the presence of either MIP1 allele.
      Thus, multiple factors can contribute to the maintenance of mitochondrial
      function, reinforcing the concept that strain background is an important
      consideration in both designing experiments and comparing results obtained by
      different research groups.

PMID- 19160454
TI  - Flocculation in Saccharomyces cerevisiae is repressed by the COMPASS methylation
      complex during high-gravity fermentation.
AB  - The significance of COMPASS on silencing of the FLO and MAL genes, located close
      to telomeres, was studied in different Saccharomyces cerevisiae strains that
      fermented high concentrations of maltose (20%) with different efficiency. In one
      particular fast maltose-fermenting yeast strain, with constitutive expression of
      FLO11, the expression of FLO1, FLO5 and FLO9 was induced during fermentation of
      high concentrations of maltose or glucose. In another strain the expression of
      mainly FLO1 was induced. Mutants of these strains with a defective COMPASS,
      however, formed very large aggregates of cells earlier in the fermentation and
      more pronounced than the wild-type. The formation of the large flocs was
      dependent on calcium ions and was inhibited by mannose. The flocculation
      displayed by mutants defective in COMPASS was due to increased amounts of FLO1,
      FLO5 and FLO9 transcripts. COMPASS-mediated silencing of the MAL genes was
      detected at the later stages of fermentation in strains that fermented high
      concentrations of maltose slowly and incompletely, while silencing was not
      detectable in strains that fermented maltose fast. Thus, COMPASS, in addition to
      the MAL genes, is also involved in silencing the expression of the FLO1, FLO5 and
      FLO9 genes.

PMID- 19160455
TI  - Coding repeat instability in the FLO11 gene of Saccharomyces yeasts.
AB  - In Saccharomyces yeasts, the FLO11 gene encodes an adhesin involved in
      filamentation, invasive growth, flocculation and adherence to solid surfaces. In
      wild Saccharomyces flor yeasts, a particularly expanded FLO11 allele also confers
      to these yeasts the ability to float under stressing liquid environments. We
      report here that, under optimal laboratory conditions, the repeats domain of the
      FLO11 gene in these wild yeasts is extremely unstable. Changes in length in the
      FLO11 coding repeats domain affected Flo11p-associated functions but,
      interestingly, some of these functions were affected more than others. Therefore,
      length variations in this single gene provide a combinatorial diversity, which
      may contribute to a very rapid adaptation to fluctuating environments. Functional
      analysis of contracted alleles indicated that buoyancy was not associated to
      FLO11 length. In contrast, this property depended on the different types of
      repetitive units found in this gene. Thus, not only variations in the number of
      intragenic repeats but also the abundance and/or distribution of the different
      repetitive units may have phenotypic and evolutionary implications.

PMID- 19160456
TI  - Absence of See1p, a widely conserved Saccharomyces cerevisiae protein, confers
      both deficient heterologous protein production and endocytosis.
AB  - The uncharacterized Saccharomyces cerevisiae open reading frame (ORF) YIL064w is
      predicted to encode a cytoplasmic 28 kDa protein, recognized by sequence
      similarity as a putative S-adenosyl-L-methionine methyltransferase. A micro-scale
      screening performed in our laboratory with the EUROSCARF S. cerevisiae BY4741
      deletion mutant collection identified YIL064w deletion as negatively affecting
      secretory production of reporter alpha-amylase. The work presented here
      corroborates the later observations of the yil064w mutant in a larger-scale assay
      and shows that Yil064p is necessary for the efficient secretory production of two
      reporter proteins, murine alpha-amylase and fungal polygalacturonase. Further, we
      analysed endocytosis in the yil064w mutant strain and observed defects at both
      very early and later stages of endocytic transport in cells in the late
      logarithmic phase. The defects at very early stages may decisively account for
      the low transfection (DNA uptake by endocytosis) efficiency that we also observed
      in the yil064w mutant. These are the first in vivo data reporting a functional
      role for the protein encoded by ORF YIL064w and identify Yil064p, named here
      secretion and early endocytosis 1 protein (See1p), as a novel component of
      intracellular transport.

PMID- 19160457
TI  - Joined in death: highlights of the Sixth International Meeting on Yeast Apoptosis
      in Leuven, Belgium, 30 April-4 May 2008.
AB  - While yeast apoptosis was still a controversial issue less than 10 years ago, the
      efforts of many groups have revealed cell death mechanisms that resemble, in many
      aspects, those described for mammalian apoptosis. Here, we provide an overview of
      new insights on yeast apoptosis and the link with lifespan of yeast cells, based
      on data presented at the 6th International Meeting of Yeast Apoptosis (IMYA).
      Together, these data demonstrate the power and advantages of the yeast system to
      uncover novel cellular factors governing life and death, placing yeast at the
      forefront of apoptosis research.

PMID- 19160458
TI  - Improved tools for efficient mapping of fission yeast genes: identification of
      microtubule nucleation modifier mod22-1 as an allele of chromatin- remodelling
      factor gene swr1.
AB  - Fission yeast genes identified in genetic screens are usually cloned by
      transformation of mutants with plasmid libraries. However, for some genes this
      can be difficult, and positional cloning approaches are required. The mutation
      swi5-39 reduces recombination frequency in homozygous crosses and has been used
      as a tool in mapping gene position (Schmidt, 1993). However, strain construction
      in swi5-39-based mapping is significantly more laborious than is desirable. Here
      we describe a set of strains designed to make swi5-based mapping more efficient
      and more powerful. The first improvement is the use of a swi5Delta strain marked
      with kanamycin (G418) resistance, which greatly facilitates identification of
      swi5 mutants. The second improvement, which follows directly from the first, is
      the introduction of a large number of auxotrophic markers into mapping strains,
      increasing the likelihood of finding close linkage between a marker and the
      mutation of interest. We combine these new mapping strains with a rec12Delta
      based approach for initial mapping of a mutation to an individual chromosome.
      Together, the two methods allow an approximate determination of map position in
      only a small number of crosses. We used these to determine that mod22-1, a
      modifier of microtubule nucleation phenotypes, encodes a truncation allele of
      Swr1, a chromatin-remodelling factor involved in nucleosomal deposition of H2A.Z
      histone variant Pht1. Expression microarray analysis of mod22-1, swr1Delta and
      pht1Delta cells suggests that the modifier phenotype of mod22-1 mutants may be
      due to small changes in expression of one or more genes involved in tubulin
      function.

PMID- 19160459
TI  - Nonenzymatic biotinylation of histone H2A.
AB  - Holocarboxylase synthetase (HCS, eukaryotic enzyme) and BirA (prokaryotic) are
      biotin protein ligases that catalyze the ATP-dependent attachment of biotin to
      apocarboxylases via the reactive intermediate, bio-5'-AMP. In this study, we
      examined the in vitro mechanism of biotin attachment to histone H2A in the
      presence of HCS and BirA. The experiment derives from our observations that HCS
      is found in the nucleus of cells in addition to the cytoplasm, and it has the
      ability to attach biotin to histones in vitro (Narang et al., Hum Mol Genet 2004;
      13:15-23). Using recombinant HCS or BirA, the rate of biotin attachment was
      considerably slower with histone H2A than with the biotin binding domain of an
      apocarboxylase. However, on incubation of recombinant H2A with chemically
      synthesized bio-5'-AMP, H2A was observed to be rapidly labeled with biotin in the
      absence of enzyme. Nonenzymatic biotinylation of a truncated apocarboxylase
      (BCCP87) has been previously reported (Streaker and Beckett, Protein Sci 2006;
      15:1928-1935), though at a much slower rate than we observe for H2A. The specific
      attachment sites of nonenzymatically biotinylated recombinant H2A at different
      time points were identified using mass spectrometry, and were found to consist of
      a similar pattern of biotin attachment as seen in the presence of HCS, with
      preference for lysines in the highly basic N-terminal region of the histone. None
      of the lysine sites within H2A resembles the biotin attachment consensus sequence
      seen in carboxylases, suggesting a novel mechanism for histone biotinylation.

PMID- 19160461
TI  - 'Is my child developing normally?': a critical review of web-based resources for
      parents.
AB  - Early detection of developmental problems improves outcomes for parents and
      children. Parents want to be involved in assessment and need high-quality,
      accurate, and reliable data on child development to help monitor progress and
      inform decisions on referral. The aim of this paper is to review which websites
      are readily accessible to parents on child development and to assess their
      quality. An internet search (on Google and Yahoo) was conducted using the search
      terms 'child development', 'parenting', and 'developmental milestones'. Criteria
      were agreed for evaluating web-based resources, adapted from and based on
      previously reported methods. Data were collected on site content, diagrams and
      layout, readability (Flesch Reading Ease Scale), design, navigability, overall
      design, and interactive features. Forty-four relevant websites were identified
      for further analysis: six government, three university, 15 health-care
      professional, four American Academy of Pediatrics, 10 by journalists, and six
      undisclosed. The best websites are presented, with justification for their
      choice. Overall, information available for parents about child development is
      accurate but much of it is incomplete, unclear, or difficult to access. There is
      a need to develop an easily accessible, clear, and authoritative resource for
      parents with illustrations. Focus groups are being held to inform this research
      further.

PMID- 19160460
TI  - Positioning multiple proteins at the nanoscale with electron beam cross-linked
      functional polymers.
AB  - Constructing multicomponent protein structures that match the complexity of those
      found in nature is essential for the next generation of medical materials. In
      this report, a versatile method for precisely arranging multicomponent protein
      nanopatterns in two-dimensional single-layer or three-dimensional multilayer
      formats using electron beam lithography is described. Eight-arm poly(ethylene
      glycol)s (PEGs) were modified at the chain ends with either biotin, maleimide,
      aminooxy, or nitrilotriacetic acid. Analysis by 1H NMR spectroscopy revealed that
      the reactions were efficient and that end-group conversions were 91-100%. The
      polymers were then cross-linked onto Si surfaces using electron beams to form
      micron-sized patterns of the functional groups. Proteins with biotin binding
      sites, a free cysteine, an N-terminal alpha-oxoamide, and a histidine tag,
      respectively, were then incubated with the substrate in aqueous solutions without
      the addition of any other reagents. By fluorescence microscopy experiments it was
      determined that proteins reacted site-specifically with the exposed functional
      groups to form micropatterns. Multicomponent nanoscale protein patterns were then
      fabricated. Different PEGs with orthogonal reactivities were sequentially
      patterned on the same chip. Simultaneous assembly of two different proteins from
      a mixture of the biomolecules formed the multicomponent two-dimensional patterns.
      Atomic force microscopy demonstrated that nanometer-sized polymer patterns were
      formed, and fluorescence microscopy demonstrated that side-by-side patterns of
      the different proteins were obtained. Moreover, multilayer PEG fabrication
      produced micron- and nanometer-sized patterns of one functional group on top of
      the other. Precise three-dimensional arrangements of different proteins were then
      realized.

PMID- 19160462
TI  - Nutritional status of children with cerebral palsy in a  Brazilian tertiary-care
      teaching hospital.

PMID- 19160463
TI  - Current and future uses of the Gross Motor Function  Classification System.

PMID- 19160464
TI  - Both constraint-induced movement therapy and bimanual  training lead to improved
      performance of upper extremity  function in children with hemiplegia.

PMID- 19160465
TI  - Non-syndromic encephalocele: a 26-year experience.

PMID- 19160466
TI  - Making a case for surveillance colonoscopy in Lynch syndrome.

PMID- 19160467
TI  - Association von Willebrand's disease and nevoid basal cell  carcinoma syndrome
      (Gorlin syndrome).

PMID- 19160468
TI  - William L Gerald, M. D., Ph.D., 1954-2008.

PMID- 19160469
TI  - [Glucagonoma without diabetes mellitus].

PMID- 19160470
TI  - [Treatment of patients in private hospitals].

PMID- 19160471
TI  - Retraction notice to "Allele-specific in situ analysis of microchimerism by
      fluorescence resonance energy transfer (FRET) in nonhuman primate tissues" [Hum
      Immunol (2002) 108-120].

PMID- 19160472
TI  - An unusual TOM20/TOM22 bypass mechanism for the mitochondrial targeting of
      cytochrome P450 proteins containing N-terminal chimeric signals.

PMID- 19160473
TI  - Selection and sticklebacks.
AB  - Over the last decade, there has been increasing circumstantial evidence for the
      action of natural selection in the genome, arising largely from molecular genetic
      surveys of large numbers of markers. In nonmodel organisms without densely mapped
      markers, a frequently used method is to identify loci that have unusually high or
      low levels of genetic differentiation, or low genetic diversity relative to other
      populations. The paper by Makinen et al. (2008a) in this issue of Molecular
      Ecology reports the results of a survey of microsatellite allele frequencies at
      more than 100 loci in seven populations of the three-spined stickleback
      (Gasterosteus aculeatus). They show that a microsatellite locus and two indel
      markers located within the intron of the Eda gene, known to control the number of
      lateral plates in the stickleback (Fig. 1), tend to be much more highly
      genetically differentiated than other loci, a finding that is consistent with the
      action of local selection. They identify a further two independent candidates for
      local selection, and, most intriguingly, they further suggest that up to 15% of
      their loci may provide evidence of balancing selection.

PMID- 19160474
TI  - Genetic estimates of contemporary effective population size: what can they tell
      us about the importance of genetic stochasticity for wild population persistence?
AB  - Genetic stochasticity due to small population size contributes to population
      extinction, especially when population fragmentation disrupts gene flow.
      Estimates of effective population size (Ne) can therefore be informative about
      population persistence, but there is a need for an assessment of their
      consistency and informative relevance. Here we review the body of empirical
      estimates of Ne for wild populations obtained with the temporal genetic method
      and published since Frankham's (1995) review. Theoretical considerations have
      identified important sources of bias for this analytical approach, and we use
      empirical data to investigate the extent of these biases. We find that
      particularly model selection and sampling require more attention in future
      studies. We report a median unbiased Ne estimate of 260 (among 83 studies) and
      find that this median estimate tends to be smaller for populations of
      conservation concern, which may therefore be more sensitive to genetic
      stochasticity. Furthermore, we report a median Ne/N ratio of 0.14, and find that
      this ratio may actually be higher for small populations, suggesting changes in
      biological interactions at low population abundances. We confirm the role of gene
      flow in countering genetic stochasticity by finding that Ne correlates strongest
      with neutral genetic metrics when populations can be considered isolated. This
      underlines the importance of gene flow for the estimation of Ne, and of
      population connectivity for conservation in general. Reductions in contemporary
      gene flow due to ongoing habitat fragmentation will likely increase the
      prevalence of genetic stochasticity, which should therefore remain a focal point
      in the conservation of biodiversity.

PMID- 19160475
TI  - Assessment of genetic diversity in the critically endangered Australian
      corroboree frogs, Pseudophryne corroboree and Pseudophryne pengilleyi, identifies
      four evolutionarily significant units for conservation.
AB  - The iconic and brightly coloured Australian northern corroboree frog,
      Pseudophryne pengilleyi, and the southern corroboree frog, Pseudophryne
      corroboree are critically endangered and may be extinct in the wild within 3
      years. We have assembled samples that cover the current range of both species and
      applied hypervariable microsatellite markers and mitochondrial DNA sequences to
      assess the levels and patterns of genetic variation. The four loci used in the
      study were highly variable, the total number of alleles observed ranged from 13
      to 30 and the average number of alleles per locus was 19. Expected heterozygosity
      of the four microsatellite loci across all populations was high and varied
      between 0.830 and 0.935. Bayesian clustering analyses in STRUCTURE strongly
      supported four genetically distinct populations, which correspond exactly to the
      four main allopatric geographical regions in which the frogs are currently found.
      Individual analyses performed on the separate regions showed that breeding sites
      within these four regions could not be separated into distinct populations.
      Twelve mtND2 haplotypes were identified from 66 individuals from throughout the
      four geographical regions. A statistical parsimony network of mtDNA haplotypes
      shows two distinct groups, which correspond to the two species of corroboree
      frog, but with most of the haplotype diversity distributed in P. pengilleyi.
      These results demonstrate an unexpectedly high level of genetic diversity in both
      species. Our data have important implications for how the genetic diversity is
      managed in the future. The four evolutionarily significant units must be
      protected and maintained in captive breeding programmes for as long as it is
      possible to do.

PMID- 19160477
TI  - In-stream and overland dispersal across a river network influences gene flow in a
      freshwater insect, Calopteryx splendens.
AB  - Gene flow in riverine species is constrained by the dendritic (branching)
      structure of the river network. Spatial genetic structure (SGS) of freshwater
      insects is particularly influenced by catchment characteristics and land use in
      the surroundings of the river. Gene flow also depends on the life cycle of
      organisms. Aquatic larvae mainly drift downstream whereas flying adults can
      disperse actively overland and along watercourses. In-stream movements can
      generate isolation by distance (IBD) at a local scale and differentiation between
      subcatchments. However, these patterns can be disrupted by overland dispersal. We
      studied SGS across the Loire River in the damselfly Calopteryx splendens which is
      able to disperse along and between watercourses. Our sampling design allowed us
      to test for overland dispersal effects on genetic differentiation between
      watercourses. Amplified fragment length polymorphism markers revealed high
      genetic differentiation at the catchment scale but the genetic structure did not
      reflect the geographical structure of sampling sites. We observed IBD patterns
      when considering the distance following the watercourse but also the Euclidean
      distance, i.e. the shortest distance, between pairs of sites. Altogether, our
      results support the hypothesis of overland dispersal between watercourses. From a
      conservation perspective, attention should be paid to the actual pathways of gene
      flow across complex landscapes such as river networks.

PMID- 19160476
TI  - Differentiating salmon populations at broad and fine geographical scales with
      microsatellites and single nucleotide polymorphisms.
AB  - Single nucleotide polymorphisms (SNPs) are appealing genetic markers due to
      several beneficial attributes, but uncertainty remains about how many of these bi
      allelic markers are necessary to have sufficient power to differentiate
      populations, a task now generally accomplished with highly polymorphic
      microsatellite markers. In this study, we tested the utility of 37 SNPs and 13
      microsatellites for differentiating 29 broadly distributed populations of Chinook
      salmon (n = 2783). Information content of all loci was determined by In and
      G'(ST), and the top 12 markers ranked by In were microsatellites, but the 6
      highest, and 7 of the top 10 G'(ST) ranked markers, were SNPs. The mean ratio of
      random SNPs to random microsatellites ranged from 3.9 to 4.1, but this ratio was
      consistently reduced when only the most informative loci were included.
      Individual assignment test accuracy was higher for microsatellites (73.1%) than
      SNPs (66.6%), and pooling all 50 markers provided the highest accuracy (83.2%).
      When marker types were combined, as few as 15 of the top ranked loci provided
      higher assignment accuracy than either microsatellites or SNPs alone. Neighbour
      joining dendrograms revealed similar clustering patterns and pairwise tests of
      population differentiation had nearly identical results with each suite of
      markers. Statistical tests and simulations indicated that closely related
      populations were better differentiated by microsatellites than SNPs. Our results
      indicate that both types of markers are likely to be useful in population
      genetics studies and that, in some cases, a combination of SNPs and
      microsatellites may be the most effective suite of loci.

PMID- 19160478
TI  - Male-biased dispersal in a tropical Australian snake (Stegonotus cucullatus,
      Colubridae).
AB  - Sex-based differences in dispersal distances can affect critical population
      parameters such as inbreeding rates and the spatial scale of local adaptation.
      Males tend to disperse further than females in mammals, whereas the reverse is
      true for birds; too few reptiles have been studied to reveal generalities for
      that group. Although reptiles are most diverse and abundant in the tropics, few
      tropical reptiles have been studied in this respect. We combine data from a long
      term (10-year) mark-recapture study with genetic information (based on nine
      microsatellite markers) on slatey-grey snakes (Stegonotus cucullatus, Colubridae)
      in the Australian wet-dry tropics. Males attain larger body sizes than females,
      and both genetic and mark-recapture data show that males also disperse further
      than females. Recapture records show that hatchling males dispersed away from
      their release points whereas hatchling females did not, and adult males moved
      further than adult females. In the genetic analysis, males contributed less to
      overall FST and relatedness than did females (F(STm) = 0.0025, F(STf) = 0.0275, P
      < 0.001; r(m) = 0.0053; r(f) = 0.0550; P < 0.001). Spatial autocorrelation
      analyses within the largest population revealed a similar pattern, with spatial
      structuring stronger for females than males. Overall, our genetic analyses not
      only supported the mark-recapture data, but also extended our insights by
      revealing occasional long-distance dispersal not detected by the mark-recapture
      study.

PMID- 19160480
TI  - Landscape genetics, historical isolation and cross-Andean gene flow in the wax
      palm, Ceroxylon echinulatum (Arecaceae).
AB  - Knowledge of the role of landscapes in shaping genetic connectivity and
      divergence is essential for understanding patterns of biogeography and diversity.
      This is particularly relevant for the Andes region, a major biodiversity hotspot
      of relatively recent origin. We examined the phylogeography and landscape
      genetics of the Andean wax palm Ceroxylon echinulatum (Arecaceae) that occurs in
      two narrow bands of montane forests on each side of the Andes in Ecuador and
      northeastern Peru. First, we tested the hypothesis of C. echinulatum being a
      geographic cline species crossing the Andes in the Amotape-Huancabamba zone (AHZ)
      of southern Ecuador/northern Peru, as indicated by observations on fruit
      morphology. Second, we assessed the timeframe of cross-Andean divergence, and
      third, we investigated the impact of contemporary and historical landscape
      features on observed spatio-genetic patterns. Individual-based Bayesian
      clustering (BC) identified a northeastern, southeastern, southwestern, and
      northwestern cluster, with areas of genetic discontinuity coinciding with the
      Andes and the Giron-Paute deflection. F-statistics derived from BC suggested an
      east-to-west dispersal history. Population-based analyses revealed strong genetic
      structuring at both small and large geographic scales. Interpopulation
      relationships and Mantel tests strongly supported the cline model with cross
      Andean dispersal in the AHZ. Along the cline, gene flow measured as F(ST) was
      mainly limited by distance, with less but significant impact of climatic
      friction. Coalescent analysis revealed that cross-Andean divergence took place
      during the Quaternary. Significant historical isolation (R(ST) > F(ST)) was found
      in the southwestern population. The current study illustrates a joint effect of
      founder dynamics, divergence by distance and historical isolation on patterns of
      Andean diversity and distribution.

PMID- 19160481
TI  - A comparison of techniques for assessing dispersal behaviour in gundis: revealing
      dispersal patterns in the absence of observed dispersal behaviour.
AB  - Knowledge of the dispersal status of group members is important to understanding
      how sociality may have evolved within a species. I assessed the effectiveness of
      four techniques for elucidating dispersal behaviour in a rock-dwelling rodent
      (Ctenodactylus gundi) with small group sizes (2-10 animals): genetic parentage
      assignment, haplotype data and kinship analyses, assignment testing, and F
      statistics. The first two methods provided the greatest insight into gundi
      dispersal behaviour. Assignment testing and F-statistics proved of limited use
      for elucidating fine-scale dispersal, but could detect large-scale patterns
      despite low sex-biased dispersal intensity (1.9 : 1) because of moderate genetic
      differentiation among groups (F(ST) = 0.10). Findings are discussed in light of
      current dispersal theory. In general, gundi dispersal is plastic, and seems to be
      dependent on body weight (for males), group composition, and scale of analysis
      (total dispersal events recorded within the population were almost twice the
      immigration rate into the population). Most groups were comprised of a single
      matriline and one immigrant male. Immigrant rather than philopatric males bred
      with group females. Dispersal amonggroups was male-biased, but dispersal or
      philopatry could occur by either sex. During a drought, both sexes delayed
      dispersal and cooperative social units formed. Whether such behaviour resulted
      directly from the drought or not remains unclear, however, since comparative
      information was not available from nondrought years. Combining fine-scale
      analyses with information on large-scale patterns provided substantial insight
      into gundi dispersal behaviour despite the limited movement of animals during a
      drought, and may prove useful for elucidating dispersal behaviour in other social
      animals.

PMID- 19160479
TI  - Mitochondrial DNA-inferred population structure and demographic history of the
      mitten crab (Eriocheir sensu stricto) found along the coast of mainland China.
AB  - The mitten crab, Eriocheir sensu stricto, is economically important in East Asia,
      although it is an invasive species in Europe and North America. Little is known
      about its population structure and historical demography in its native range,
      especially along the Pacific coast of China. We collected mitochondrial
      cytochrome oxidase subunit II and cytochrome b sequences from 154 individuals
      distributed in the rivers along the Chinese coast and 15 individuals from Japan.
      Phylogenetic analysis resulted in three major monophyletic groups: northern
      China, southern China and Japan. Negligible migration was detected among those
      groups by coalescent analysis. Hence, we support the recognition of three
      species: Eriocheir hepuensis in southern China, Eriocheir sinensis in northern
      China and Eriocheir japonica in Japan. The populations in the middle (the Oujiang
      and Minjiang Rivers) possess a mixture of haplotypes similar to either the
      northern or the southern haplotypes. We believe that secondary intergradation as
      the most likely cause of the clinal variation based on examining the genetic
      variation in the latitudinal space. The estimated divergence time between E.
      sinensis and E. hepuensis is 2.24 million years ago (Ma), while the divergence
      time between E. japonica and E. sinensis is 1.83 Ma. Both are in the late
      Pliocene, suggesting that land bridges associated with low sea level during that
      time might have severed as vicariant barriers for speciation. The divergence of
      the northern population and the 'northern haplotypes' in the middle population
      was estimated at 0.12 Ma, while the time separating the southern population and
      the 'southern haplotypes' in the middle populations was estimated as 0.16 Ma,
      implicating possible secondary contact in the late Pleistocene.

PMID- 19160482
TI  - Population genetic structure, gene flow and sex-biased dispersal in frillneck
      lizards (Chlamydosaurus kingii).
AB  - By using both mitochondrial and nuclear multiloci markers, we explored population
      genetic structure, gene flow and sex-specific dispersal of frillneck lizards
      (Chlamydosaurus kingii) sampled at three locations, separated by 10 to 50 km, in
      a homogenous savannah woodland in tropical Australia. Apart from a recombinant
      lizard, the mitochondrial analyses revealed two nonoverlapping
      haplotypes/populations, while the nuclear markers showed that the frillneck
      lizards represented three separate clusters/populations. Due to the small
      population size of the mtDNA, fixation may occur via founder effects and/or
      drift. We therefore suggest that either of these two processes, or a combination
      of the two, are the most likely causes of the discordant results obtained from
      the mitochondrial and the nuclear markers. In contrast to the nonoverlapping
      mitochondrial haplotypes, in 12 out of 74 lizards, mixed nuclear genotypes were
      observed, hence revealing a limited nuclear gene flow. Although gene flow should
      ultimately result in a blending of the populations, we propose that the distinct
      nuclear population structure is maintained by frequent fires resulting in local
      bottlenecks, and concomitant spatial separation of the frillneck lizard
      populations. Limited mark-recapture data and the difference in distribution of
      the mitochondrial and nuclear markers suggest that the mixed nuclear genotypes
      were caused by juvenile male-biased dispersal.

PMID- 19160483
TI  - Identification of genes that regulate epithelial cell migration using an siRNA
      screening approach.
AB  - To provide a systematic analysis of genes that regulate epithelial cell
      migration, we performed a high throughput wound healing screen with MCF-10A
      breast epithelial cells, using siRNAs targeting 1,081 human genes encoding
      phosphatases, kinases and proteins predicted to influence cell migration and
      adhesion. The primary screen identified three categories of hits: those that
      accelerate, those that inhibit and those that impair migration with associated
      effects on cell proliferation or metabolism. Extensive validation of all the hits
      yielded 66 high confidence genes that, when downregulated, either accelerated or
      impaired migration; 42 of these high confidence genes have not been previously
      associated with motility or adhesion. Time-lapse video microscopy revealed a
      broad spectrum of phenotypic changes involving alterations in the extent and
      nature of disruption of cell-cell adhesion, directionality of motility, cell
      polarity and shape, and protrusion dynamics. Informatics analysis highlighted
      three major signalling nodes, beta-catenin, beta1-integrin and actin, and a large
      proportion of the genes that accelerated migration impaired cell-cell adhesion.

PMID- 19160484
TI  - Actin and alpha-actinin orchestrate the assembly and maturation of nascent
      adhesions in a myosin II motor-independent manner.
AB  - Using two-colour imaging and high resolution TIRF microscopy, we investigated the
      assembly and maturation of nascent adhesions in migrating cells. We show that
      nascent adhesions assemble and are stable within the lamellipodium. The assembly
      is independent of myosin II but its rate is proportional to the protrusion rate
      and requires actin polymerization. At the lamellipodium back, the nascent
      adhesions either disassemble or mature through growth and elongation. Maturation
      occurs along an alpha-actinin-actin template that elongates centripetally from
      nascent adhesions. Alpha-Actinin mediates the formation of the template and
      organization of adhesions associated with actin filaments, suggesting that actin
      crosslinking has a major role in this process. Adhesion maturation also requires
      myosin II. Rescue of a myosin IIA knockdown with an actin-bound but motor
      inhibited mutant of myosin IIA shows that the actin crosslinking function of
      myosin II mediates initial adhesion maturation. From these studies, we have
      developed a model for adhesion assembly that clarifies the relative contributions
      of myosin II and actin polymerization and organization.

PMID- 19160485
TI  - A ribosomal protein L23-nucleophosmin circuit coordinates Mizl function with cell
      growth.
AB  - The Myc-associated zinc-finger protein, Miz1, is a negative regulator of cell
      proliferation and induces expression of the cell-cycle inhibitors p15(Ink4b) and
      p21(Cip1). Here we identify the ribosomal protein L23 as a negative regulator of
      Miz1-dependent transactivation. L23 exerts this function by retaining
      nucleophosmin, an essential co-activator of Miz1 required for Miz1-induced cell
      cycle arrest, in the nucleolus. Mutant forms of nucleophosmin found in acute
      myeloid leukaemia fail to co-activate Miz1 and re-localize it to the cytosol. As
      L23 is encoded by a direct target gene of Myc, this regulatory circuit may
      provide a feedback mechanism that links translation of Myc target genes and cell
      growth to Miz1-dependent cell-cycle arrest.

PMID- 19160486
TI  - Talin depletion reveals independence of initial cell spreading from integrin
      activation and traction.
AB  - Cell spreading, adhesion and remodelling of the extracellular matrix (ECM)
      involve bi-directional signalling and physical linkages between the ECM,
      integrins and the cell cytoskeleton. The actin-binding proteins talin1 and 2 link
      ligand-bound integrins to the actin cytoskeleton and increase the affinity of
      integrin for the ECM. Here we report that depletion of talin2 in talin1-null
      (talin1(-/-)) cells did not affect the initiation of matrix-activated spreading
      or Src family kinase (SFK) activation, but abolished the ECM-integrin
      cytoskeleton linkage and sustained cell spreading and adhesion. Specifically,
      focal adhesion assembly, focal adhesion kinase (FAK) signalling and traction
      force generation on substrates were severely affected. The talin1 head domain
      restored beta1 integrin activation but only full-length talin1 restored the ECM
      cytoskeleton linkage and normal cytoskeleton organization. Our results
      demonstrate three biochemically distinct steps in fibronectin-activated cell
      spreading and adhesion: (1) fibronectin-integrin binding and initiation of
      spreading, (2) fast cell spreading and (3) focal adhesion formation and substrate
      traction. We suggest that talin is not required for initial cell spreading.
      However, talin provides the important mechanical linkage between ligand-bound
      integrins and the actin cytoskeleton required to catalyse focal adhesion
      dependent pathways.

PMID- 19160487
TI  - Epigenetic control of polyamines by the prion [PSI+].
AB  - Prion proteins are found in mammals and yeast, and can transmit diseases and
      encode heritable phenotypic traits. In Saccharomyces cerevisiae, eRF3, Rnq1, Ure2
      and Swil are functional proteins with a soluble conformation that can switch to a
      non-functional, amyloid conformation denoted as [PSI+], [PIN+], [URE3] and
      [SWI+], respectively. The prion [PSI+] corresponds to an aggregated conformation
      of the translational release factor eRF3, which suppresses nonsense codons.
      [PSI+] modifies cellular fitness and induces several phenotypes according to the
      genetic background. An elegant series of studies has demonstrated that several
      [PSI+]-induced phenotypes occur as a consequence of decreased translational
      termination efficiency. However, the genes whose expression levels are controlled
      by [PSI+] remain largely unknown. Here, we show that [PSI+] enhances expression
      of antizyme, a negative regulator of cellular polyamines, by modulating the +1
      frameshifting required for its expression. Our study also demonstrates that
      [PSI+] greatly affects cellular polyamines in yeast. We show that modification of
      the cellular content of polyamines by the prion accounts for half of the [PSI+]
      induced phenotypes. Antizyme is the first protein to be described for which
      expression of its functional form is stimulated by [PSI+].

PMID- 19160488
TI  - Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme
      required for mitotic progression.
AB  - Proper control of entry into and progression through mitosis is essential for
      normal cell proliferation and the maintenance of genome stability. The mammalian
      mitotic kinase Polo-like kinase 1 (Plk1) is involved in multiple stages of
      mitosis5. Here we report that Forkhead Box M1 (FoxM1), a substrate of Plk1,
      controls a transcriptional programme that mediates Plk1-dependent regulation of
      cell-cycle progression. The carboxy-terminal domain of FoxM1 binds Plk1, and
      phosphorylation of two key residues in this domain by Cdk1 is essential for Plk1
      FoxM1 interaction. Formation of the Plk1-FoxM1 complex allows for direct
      phosphorylation of FoxM1 by Plk1 at G2/M and the subsequent activation of FoxM1
      activity, which is required for expression of key mitotic regulators, including
      Plk1 itself. Thus, Plk1-dependent regulation of FoxM1 activity provides a
      positive-feedback loop ensuring tight regulation of transcriptional networks
      essential for orderly mitotic progression.

PMID- 19160489
TI  - The adaptor protein of the anaphase promoting complex Cdh1 is essential in
      maintaining replicative lifespan and in learning and memory.
AB  - The anaphase promoting complex (APC) or cyclosome is a multisubunit E3 ubiquitin
      ligase. Cdc20 (fizzy (fzy)) or p55CDC, and Cdh1 (Hct1, srw1 or fizzy-related 1
      (fzr1)) encode two adaptor proteins that bring substrates to the APC. Both APC
      Cdc20 and APC-Cdh1 have been implicated in the control of mitosis through
      mediating ubiquitination of mitotic regulators, such as cyclin B1 and securin.
      However, the importance of Cdh1 function in vivo and whether its function is
      redundant with that of Cdc20 are unclear. Here we have analysed mice lacking
      Cdh1. We show that Cdh1 is essential for placental development and that its
      deficiency causes early lethality. Cdhl-deficient mouse embryonic fibroblasts
      (MEFs) entered replicative senescence prematurely because of stabilization of
      Ets2 and subsequent activation of p6(Ink4a) expression. These results have
      uncovered an unexpected role of the APC in maintaining replicative lifespan of
      MEFs. Further, Cdh1 heterozygous mice show defects in late-phase long-term
      potentiation (L-LTP) in the hippocampus and are deficient in contextual fear
      conditioning, suggesting that Cdh1 has a role in learning and memory.

PMID- 19160490
TI  - Reduced cytosolic protein synthesis suppresses mitochondrial degeneration.
AB  - Mitochondrial function degenerates with ageing and in ageing-related
      neuromuscular degenerative diseases, causing physiological decline of the cell.
      Factors that can delay the degenerative process are actively sought after. Here,
      we show that reduced cytosolic protein synthesis is a robust cellular strategy
      that suppresses ageing-related mitochondrial degeneration. We modelled autosomal
      dominant progressive external ophthalmoplegia (adPEO), an adult- or later-onset
      degenerative disease, by introducing the A128P mutation into the adenine
      nucleotide translocase Aac2p of Saccharomyces cerevisiae. The aac2(A128P) allele
      dominantly induces ageing-dependent mitochondrial degeneration and phenotypically
      tractable degenerative cell death, independently of its ADP/ATP exchange
      activity. Mitochondrial degeneration was suppressed by lifespan-extending
      nutritional interventions and by eight longevity mutations, which are all known
      to reduce cytosolic protein synthesis. These longevity interventions also
      independently suppressed ageing-related mitochondrial degeneration in the pro
      ageing prohibitin mutants. The aac2(A128P) mutant has reduced mitochondrial
      membrane potential (delta psi(m)) and is synthetically lethal to low delta psi(m)
      conditions, including the loss of prohibitin. Mitochondrial degeneration was
      accelerated by defects in protein turnover on the inner membrane and was
      suppressed by cycloheximide, a specific inhibitor of cytosolic ribosomes. Reduced
      cytosolic protein synthesis suppressed membrane depolarization and defects in
      mitochondrial gene expression in aac(A128P) cells. Our finding thus establishes a
      link between protein homeostasis (proteostasis), cellular bioenergetics and
      mitochondrial maintenance during ageing.

PMID- 19160491
TI  - P53 mRNA controls p53 activity by managing Mdm2 functions.
AB  - The E3 ubiquitin ligase Mdm2 is a focal regulator of p53 tumour suppressor
      activity. It binds p53, promoting its polyubiquitination and degradation, and
      also controls p53 synthesis. However, it is not known how this dual function of
      Mdm2 on p53 synthesis and degradation is achieved. Here we show that the p53 mRNA
      region encoding the Mdm2-binding site interacts directly with the RING domain of
      Mdm2. This impairs the E3 ligase activity of Mdm2 and promotes p53 mRNA
      translation. We also show that introduction of cancer-derived single silent point
      mutations in the p53 mRNA weakens its binding to Mdm2 and results in reduced p53
      activity. These data are consistent with a mechanism by which changes in silent
      nucleotides can affect the function of the encoded protein, and indicate that
      Mdm2-mediated control of p53 synthesis and degradation has evolved in the p53
      mRNA sequence and its encoded amino acids.

PMID- 19160492
TI  - Ripples from neighbouring transcription.
AB  - Transcriptional initiation of each gene is assumed to be independently controlled
      in mammals. On the other hand, recent large-scale transcriptome analyses have
      shown that the genome is pervasively transcribed, such that the most of its DNA
      gives rise to RNAs. This raises the question of whether it is possible to
      pinpoint and activate a particular locus without perturbing numerous neighbouring
      transcripts. Here we show that intensive transcription at one locus frequently
      spills over into its physical neighbouring loci. Rapid induction of immediate
      early genes (IEGs) in response to growth factor stimulations is accompanied by co
      upregulation of their neighbouring genes. Profiling the primary transcripts in
      the nucleus with whole-genome tiling arrays delineated simultaneous activation of
      transcription centred on IEGs. Even in surrounding intergenic regions,
      transcriptional activation took place at the same time. Acetylation levels of
      histone H3 and H4 are elevated along with the IEG induction and neighbouring co
      upregulation. Inhibition of the mitogen-activated protein kinase (MAPK) pathway
      or the transcription factor SRF suppresses all transcriptional upregulation.
      These results suggest that transcriptional activation has a ripple effect, which
      may be advantageous for coordinated expression.

PMID- 19160493
TI  - Epigenetic transcriptional repression of cellular genes by a viral SET protein.
AB  - Viruses recruit host proteins to secure viral genome maintenance and replication.
      However, whether they modify host histones directly to interfere with chromatin
      based transcription is unknown. Here we report that Paramecium bursaria chlorella
      virus 1 (PBCV-1) encodes a functional SET domain histone Lys methyltransferase
      (HKMTase) termed vSET, which is linked to rapid inhibition of host transcription
      after viral infection. We show that vSET is packaged in the PBCV-1 virion, and
      that it contains a nuclear localization signal and probably represses host
      transcription by methylating histone H3 at Lys 27 (H3K27), a modification known
      to trigger gene silencing in eukaryotes. We also show that vSET induces cell
      accumulation at the G2/M phase by recruiting the Polycomb repressive complex CBX8
      to the methylated H3K27 site in a heterologous system, vSET-like proteins that
      have H3K27 methylation activity are conserved in chlorella viruses. Our findings
      suggest a viral mechanism to repress gene transcription by direct modification of
      chromatin by PBCV-1 vSET.

PMID- 19160494
TI  - Pubertal hormones modulate the addition of new cells to sexually dimorphic brain
      regions.
AB  - New cells, including neurons, arise in several brain regions during puberty in
      rats. Sex differences in pubertal addition of cells coincide with adult sexual
      dimorphisms: for each region, the sex that gains more cells during puberty has a
      larger volume in adulthood. Removing gonadal hormones before puberty eliminates
      these sex differences, indicating that gonadal steroids direct the addition of
      new cells during puberty to maintain and accentuate sexual dimorphisms in the
      adult brain.

PMID- 19160495
TI  - Synaptic release of GABA by AgRP neurons is required for normal regulation of
      energy balance.
AB  - The physiologic importance of GABAergic neurotransmission in hypothalamic
      neurocircuits is unknown. To examine the importance of GABA release from agouti
      related protein (AgRP) neurons (which also release AgRP and neuropeptide Y), we
      generated mice with an AgRP neuron-specific deletion of vesicular GABA
      transporter. These mice are lean, resistant to obesity and have an attenuated
      hyperphagic response to ghrelin. Thus, GABA release from AgRP neurons is
      important in regulating energy balance.

PMID- 19160496
TI  - Serotonergic transcriptional programming determines maternal behavior and
      offspring survival.
AB  - Central serotonergic signaling influences many physiological processes, but a
      requirement for reproductive success has not been demonstrated. Using mouse dams
      with a specific disruption in serotonin neuron development, we found that
      serotonergic function is required for the nurturing and survival of offspring.
      Full rescue of survival depended on the mother's expression level of the upstream
      serotonergic transcriptional cascade. Thus, intrinsic transcriptional programming
      of maternal serotonergic activity determines the quality of nurturing and whether
      or not the organism survives.

PMID- 19160497
TI  - Neural repetition suppression reflects fulfilled perceptual expectations.
AB  - Stimulus-evoked neural activity is attenuated on stimulus repetition (repetition
      suppression), a phenomenon that is attributed to largely automatic processes in
      sensory neurons. By manipulating the likelihood of stimulus repetition, we found
      that repetition suppression in the human brain was reduced when stimulus
      repetitions were improbable (and thus, unexpected). Our data suggest that
      repetition suppression reflects a relative reduction in top-down perceptual
      'prediction error' when processing an expected, compared with an unexpected,
      stimulus.

PMID- 19160498
TI  - Pore region of TRPV3 ion channel is specifically required for heat activation.
AB  - Ion channels can be activated (gated) by a variety of stimuli, including
      chemicals, voltage, mechanical force or temperature. Although molecular
      mechanisms of ion channel gating by chemical and voltage stimuli are understood
      in principal, the mechanisms of temperature activation remain unknown. The
      transient receptor potential channel TRPV3 is a nonselective cation channel that
      is activated by warm temperatures and sensory chemicals such as camphor. Here we
      screened approcimately 14,000 random mutant clones of mouse TRPV3 and identified
      five single point mutations that specifically abolish heat activation but do not
      perturb chemical activation or voltage modulation. Notably, all five mutations
      are located in the putative sixth transmembrane helix and the adjacent
      extracellular loop in the pore region of mouse TRPV3. Although distinct in
      sequence, we found that the corresponding loop of frog TRPV3 is also specifically
      required for heat activation. These findings demonstrate that the temperature
      sensitivity of TRPV3 is separable from all other known activation mechanisms and
      implicate a specific region in temperature sensing.

PMID- 19160499
TI  - Requirement for COUP-TFI and II in the temporal specification of neural stem
      cells in CNS development.
AB  - In the developing CNS, subtypes of neurons and glial cells are generated
      according to a schedule that is defined by cell-intrinsic mechanisms that
      function at the progenitor-cell level. However, no critical molecular switch for
      the temporal specification of CNS progenitor cells has been identified. We found
      that chicken ovalbumin upstream promoter-transcription factor I and II (Coup-tfI
      and Coup-tfII, also known as Nr2f1 and Nr2f2) are required for the temporal
      specification of neural stem/progenitor cells (NSPCs), including their
      acquisition of gliogenic competence, as demonstrated by their responsiveness to
      gliogenic cytokines. COUP-TFI and II are transiently co-expressed in the
      ventricular zone of the early embryonic CNS. The double knockdown of Coup-tfI/II
      in embryonic stem cell (ESC)-derived NSPCs and the developing mouse forebrain
      caused sustained neurogenesis and the prolonged generation of early-born neurons.
      These findings reveal a part of the timer mechanisms for generating diverse types
      of neurons and glial cells during CNS development.

PMID- 19160500
TI  - Age-dependent epigenetic control of differentiation inhibitors is critical for
      remyelination efficiency.
AB  - The efficiency of remyelination decreases with age, but the molecular mechanisms
      responsible for this decline remain only partially understood. In this study, we
      show that remyelination is regulated by age-dependent epigenetic control of gene
      expression. In demyelinated young brains, new myelin synthesis is preceded by
      downregulation of oligodendrocyte differentiation inhibitors and neural stem cell
      markers, and this is associated with recruitment of histone deacetylases (HDACs)
      to promoter regions. In demyelinated old brains, HDAC recruitment is inefficient,
      and this allows the accumulation of transcriptional inhibitors and prevents the
      subsequent surge in myelin gene expression. Defective remyelination can be
      recapitulated in vivo in mice receiving systemic administration of
      pharmacological HDAC inhibitors during cuprizone treatment and is consistent with
      in vitro results showing defective differentiation of oligodendrocyte progenitors
      after silencing specific HDAC isoforms. Thus, we suggest that inefficient
      epigenetic modulation of the oligodendrocyte differentiation program contributes
      to the age-dependent decline in remyelination efficiency.

PMID- 19160501
TI  - Serine phosphorylation of ephrinB2 regulates trafficking of synaptic AMPA
      receptors.
AB  - Plasticity in the brain is essential for maintaining memory and learning and is
      associated with the dynamic membrane trafficking of AMPA receptors. EphrinB
      proteins, ligands for EphB receptor tyrosine kinases, are transmembrane molecules
      with signaling capabilities that are required for spine morphogenesis, synapse
      formation and synaptic plasticity. Here, we describe a molecular mechanism for
      ephrinB2 function in controlling synaptic transmission. EphrinB2 signaling is
      critical for the stabilization of AMPA receptors at the cellular membrane. Mouse
      hippocampal neurons from conditional ephrinB2 knockouts showed enhanced
      constitutive internalization of AMPA receptors and reduced synaptic transmission.
      Mechanistically, glutamate receptor interacting proteins bridge ephrinB ligands
      and AMPA receptors. Moreover, this function involved a regulatory aspect of
      ephrinB reverse signaling that involves the phosphorylation of a single serine
      residue in their cytoplasmic tails. In summary, our findings uncover a model of
      cooperative AMPA receptor and ephrinB reverse signaling at the synapse.

PMID- 19160502
TI  - GABAergic synapses are formed without the involvement of dendritic protrusions.
AB  - Synaptogenesis and the role of dendritic protrusions in this process are well
      studied in glutamatergic synapses. Much less is known about the formation of
      GABAergic synapses, which are located predominantly on the dendritic shaft. We
      used genetically labeled interneurons in mature hippocampal slice cultures and
      two-photon laser-scanning microscopy to examine contact formation between
      GABAergic axons and the dendrites of CA1 pyramidal cells. Dendritic protrusions
      distinguished and selected between glutamatergic and GABAergic boutons. In
      contrast with contacts with glutamatergic boutons, which can be long lasting, the
      contacts of dendritic protrusions with GABAergic boutons were always short lived.
      Similarly, the contacts made by GABAergic axonal protrusions were always
      transient. New putative GABAergic synapses were formed exclusively by new boutons
      appearing at pre-existing axon-dendrite crossings without the involvement of any
      dendritic or axonal protrusions. These findings imply that fundamentally
      different mechanisms underlie the generation of GABAergic and glutamatergic
      synapses.

PMID- 19160503
TI  - Prefrontal cortex AMPA receptor plasticity is crucial for cue-induced relapse to
      heroin-seeking.
AB  - Associative learning processes have an important role in the initiation and
      persistence of heroin-seeking. Here we show in a rat self-administration model
      that reexposure to cues previously associated with heroin results in
      downregulation of AMPA receptor subunit GluR2 and concomitant upregulation of
      clathrin-coat assembly protein AP2ml in synaptic membranes of the medial
      prefrontal cortex (mPFC). Reduced AMPA receptor expression in synaptic membranes
      was associated with a decreased AMPA/NMDA current ratio and increased
      rectification index in mPFC pyramidal neurons. Systemic or ventral (but not
      dorsal) mPFC injections of a peptide inhibiting GluR2 endocytosis attenuated both
      the rectification index and cue-induced relapse to heroin-seeking, without
      affecting sucrose-seeking. We conclude that GluR2 receptor endocytosis and the
      resulting synaptic depression in ventral mPFC are crucial for cue-induced relapse
      to heroin-seeking. As reexposure to conditioned stimuli is a major cause for
      heroin relapse, inhibition of GluR2 endocytosis may provide a new target for the
      treatment of heroin addiction.

PMID- 19160504
TI  - A subset of octopaminergic neurons are important for Drosophila aggression.
AB  - Aggression is an innate behavior that is important for animal survival and
      evolution. We examined the molecular and cellular mechanisms underlying
      aggression in Drosophila. Reduction of the neurotransmitter octopamine, the
      insect equivalent of norepinephrine, decreased aggression in both males and
      females. Mutants lacking octopamine did not initiate fighting and did not fight
      other flies, although they still provoked other flies to fight themselves. Mutant
      males lost to the wild-type males in fighting and in competing for copulation
      with females. Enhanced octopaminergic signaling increased aggression in socially
      grouped flies, but not in socially isolated flies. We carried out genetic rescue
      experiments that revealed the functional importance of neuronal octopamine and
      identified a small subset of octopaminergic neurons in the suboesophageal
      ganglion as being important for aggression.

PMID- 19160505
TI  - The acute light-induction of sleep is mediated by OPN4-based photoreception.
AB  - Sleep is regulated by both homeostatic and circadian mechanisms. The latter,
      termed 'process c', helps synchronize sleep-wake patterns to the appropriate time
      of the day. However, in the absence of a circadian clock, overall sleep-wake
      rhythmicity is preserved and remains synchronized to the external light-dark
      cycle, indicating that there is an additional, clock-independent photic input to
      sleep. We found that the direct photic regulation of sleep in mice is
      predominantly mediated by melanopsin (OPN4)-based photoreception of
      photosensitive retinal ganglion cells (pRGCs). Moreover, OPN4-dependent sleep
      regulation was correlated with the activation of sleep-promoting neurons in the
      ventrolateral preoptic area and the superior colliculus. Collectively, our
      findings describe a previously unknown pathway in sleep regulation and identify
      the pRGC/OPN4 signaling system as a potentially new pharmacological target for
      the selective manipulation of sleep and arousal states.

PMID- 19160507
TI  - Emergence of binocular functional properties in a monocular neural circuit.
AB  - Sensory circuits frequently integrate converging inputs while maintaining precise
      functional relationships between them. For example, in mammals with stereopsis,
      neurons at the first stages of binocular visual processing show a close alignment
      of receptive-field properties for each eye. Still, basic questions about the
      global wiring mechanisms that enable this functional alignment remain unanswered,
      including whether the addition of a second retinal input to an otherwise
      monocular neural circuit is sufficient for the emergence of these binocular
      properties. We addressed this question by inducing a de novo binocular retinal
      projection to the larval zebrafish optic tectum and examining recipient neuronal
      populations using in vivo two-photon calcium imaging. Notably, neurons in rewired
      tecta were predominantly binocular and showed matching direction selectivity for
      each eye. We found that a model based on local inhibitory circuitry that computes
      direction selectivity using the topographic structure of both retinal inputs can
      account for the emergence of this binocular feature.

PMID- 19160506
TI  - Circadian oscillation of hippocampal MAPK activity and cAmp: implications for
      memory persistence.
AB  - The mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate
      (cAMP) signal transduction pathways have critical roles in the consolidation of
      hippocampus-dependent memory. We found that extracellular regulated kinase 1/2
      MAPK phosphorylation and cAMP underwent a circadian oscillation in the
      hippocampus that was paralleled by changes in Ras activity and the
      phosphorylation of MAPK kinase and cAMP response element-binding protein (CREB).
      The nadir of this activation cycle corresponded with severe deficits in
      hippocampus-dependent fear conditioning under both light-dark and free-running
      conditions. Circadian oscillations in cAMP and MAPK activity were absent in
      memory-deficient transgenic mice that lacked Ca2+ -stimulated adenylyl cyclases.
      Furthermore, physiological and pharmacological interference with oscillations in
      MAPK phosphorylation after the cellular memory consolidation period impaired the
      persistence of hippocampus-dependent memory. These data suggest that the
      persistence of long-term memories may depend on reactivation of the
      cAMP/MAPK/CREB transcriptional pathway in the hippocampus during the circadian
      cycle.

PMID- 19160508
TI  - Psychophysical and neurometric detection performance under stimulus uncertainty.
AB  - Signal detection theoretical analyses of spike counts have revealed that some
      cortical neurons can exceed psychophysical sensitivity in cases where a sensory
      signal is specified exactly. It is not known whether this finding holds in the
      more natural situation where signal occurrence is temporally uncertain. We
      investigated the ability of rat barrel cortex neurons to detect faint and
      transient whisker deflections occurring at unspecified times. The progression
      from fully specified stimuli to temporal uncertainty degraded neuronal
      sensitivity such that it seems highly unlikely that single neurons can provide
      the basis for decoding uncertain perceptual events. However, modeling the
      sensitivity of neuronal pools on basis of spike timing precision across several
      neurons in an optimal encoding window of 25 ms showed that the subject's
      perceptual sensitivity could be based on the occurrence of coincident spikes from
      four to five neurons.

PMID- 19160510
TI  - Action anticipation and motor resonance in elite basketball players.
AB  - We combined psychophysical and transcranial magnetic stimulation studies to
      investigate the dynamics of action anticipation and its underlying neural
      correlates in professional basketball players. Athletes predicted the success of
      free shots at a basket earlier and more accurately than did individuals with
      comparable visual experience (coaches or sports journalists) and novices.
      Moreover, performance between athletes and the other groups differed before the
      ball was seen to leave the model's hands, suggesting that athletes predicted the
      basket shot's fate by reading the body kinematics. Both visuo-motor and visual
      experts showed a selective increase of motor-evoked potentials during observation
      of basket shots. However, only athletes showed a time-specific motor activation
      during observation of erroneous basket throws. Results suggest that achieving
      excellence in sports may be related to the fine-tuning of specific anticipatory
      'resonance' mechanisms that endow elite athletes' brains with the ability to
      predict others' actions ahead of their realization.

PMID- 19160511
TI  - Target practice.

PMID- 19160509
TI  - Interhemispheric correlations of slow spontaneous neuronal fluctuations revealed
      in human sensory cortex.
AB  - Animal studies have shown robust electrophysiological activity in the sensory
      cortex in the absence of stimuli or tasks. Similarly, recent human functional
      magnetic resonance imaging (fMRI) revealed widespread, spontaneously emerging
      cortical fluctuations. However, it is unknown what neuronal dynamics underlie
      this spontaneous activity in the human brain. Here we studied this issue by
      combining bilateral single-unit, local field potentials (LFPs) and intracranial
      electrocorticography (ECoG) recordings in individuals undergoing clinical
      monitoring. We found slow (<0.1 Hz, following 1/f-like profiles) spontaneous
      fluctuations of neuronal activity with significant interhemispheric correlations.
      These fluctuations were evident mainly in neuronal firing rates and in gamma (40
      100 Hz) LFP power modulations. Notably, the interhemispheric correlations were
      enhanced during rapid eye movement and stage 2 sleep. Multiple intracranial ECoG
      recordings revealed clear selectivity for functional networks in the spontaneous
      gamma LFP power modulations. Our results point to slow spontaneous modulations in
      firing rate and gamma LFP as the likely correlates of spontaneous fMRI
      fluctuations in the human sensory cortex.

PMID- 19160512
TI  - Efficient microRNA capture and bar-coding via enzymatic oligonucleotide
      adenylation.
AB  - Here we report a highly efficient and simplified strategy to preadenylate bar
      coded oligonucleotides designed for microRNA (miRNA) capture and multiplex
      analysis. Using this approach, we enzymatically preadenylated bar-coded
      oligonucleotides with high efficiency when compared to the chemical method
      currently used by miRNA investigators. As a case study, we used these
      oligonucleotides in an ATP-independent ligation to miRNAs, suggesting the utility
      of our method in end-capture protocols and high-throughput sequencing
      applications.

PMID- 19160513
TI  - High-throughput, quantitative analyses of genetic interactions in E. coli.
AB  - Large-scale genetic interaction studies provide the basis for defining gene
      function and pathway architecture. Recent advances in the ability to generate
      double mutants en masse in Saccharomyces cerevisiae have dramatically accelerated
      the acquisition of genetic interaction information and the biological inferences
      that follow. Here we describe a method based on F factor-driven conjugation,
      which allows for high-throughput generation of double mutants in Escherichia
      coli. This method, termed genetic interaction analysis technology for E. coli
      (GIANT-coli), permits us to systematically generate and array double-mutant cells
      on solid media in high-density arrays. We show that colony size provides a robust
      and quantitative output of cellular fitness and that GIANT-coli can recapitulate
      known synthetic interactions and identify previously unidentified negative
      (synthetic sickness or lethality) and positive (suppressive or epistatic)
      relationships. Finally, we describe a complementary strategy for genome-wide
      suppressor-mutant identification. Together, these methods permit rapid, large
      scale genetic interaction studies in E. coli.

PMID- 19160514
TI  - Single-spike detection in vitro and in vivo with a genetic Ca2+ sensor.
AB  - Measurement of population activity with single-action-potential, single-neuron
      resolution is pivotal for understanding information representation and processing
      in the brain and how the brain's responses are altered by experience. Genetically
      encoded indicators of neuronal activity allow long-term, cell type-specific
      expression. Fluorescent Ca2+ indicator proteins (FCIPs), a main class of
      reporters of neural activity, initially suffered, in particular, from an
      inability to report single action potentials in vivo. Although suboptimal Ca2+
      binding dynamics and Ca2+-induced fluorescence changes in FCIPs are important
      factors, low levels of expression also seem to play a role. Here we report that
      delivering D3cpv, an improved fluorescent resonance energy transfer-based FCIP,
      using a recombinant adeno-associated virus results in expression sufficient to
      detect the Ca2+ transients that accompany single action potentials. In upper
      layer cortical neurons, we were able to detect transients associated with single
      action potentials firing at rates of <1 Hz, with high reliability, from in vivo
      recordings in living mice.

PMID- 19160515
TI  - A genetically encoded calcium indicator for chronic in vivo two-photon imaging.
AB  - Neurons in the nervous system can change their functional properties over time.
      At present, there are no techniques that allow reliable monitoring of changes
      within identified neurons over repeated experimental sessions. We increased the
      signal strength of troponin C-based calcium biosensors in the low-calcium regime
      by mutagenesis and domain rearrangement within the troponin C calcium binding
      moiety to generate the indicator TN-XXL. Using in vivo two-photon ratiometric
      imaging, we show that TN-XXL exhibits enhanced fluorescence changes in neurons of
      flies and mice. TN-XXL could be used to obtain tuning curves of orientation
      selective neurons in mouse visual cortex measured repeatedly over days and weeks.
      Thus, the genetically encoded calcium indicator TN-XXL allows repeated imaging of
      response properties from individual, identified neurons in vivo, which will be
      crucial for gaining new insights into cellular mechanisms of plasticity,
      regeneration and disease.

PMID- 19160516
TI  - mirWIP: microRNA target prediction based on microRNA-containing ribonucleoprotein
      enriched transcripts.
AB  - Target prediction for animal microRNAs (miRNAs) has been hindered by the small
      number of verified targets available to evaluate the accuracy of predicted miRNA
      target interactions. Recently, a dataset of 3,404 miRNA-associated mRNA
      transcripts was identified by immunoprecipitation of the RNA-induced silencing
      complex components AIN-1 and AIN-2. Our analysis of this AIN-IP dataset revealed
      enrichment for defining characteristics of functional miRNA-target interactions,
      including structural accessibility of target sequences, total free energy of
      miRNA-target hybridization and topology of base-pairing to the 5' seed region of
      the miRNA. We used these enriched characteristics as the basis for a quantitative
      miRNA target prediction method, miRNA targets by weighting immunoprecipitation
      enriched parameters (mirWIP), which optimizes sensitivity to verified miRNA
      target interactions and specificity to the AIN-IP dataset. MirWIP can be used to
      capture all known conserved miRNA-mRNA target relationships in Caenorhabditis
      elegans at a lower false-positive rate than can the current standard methods.

PMID- 19160517
TI  - Holographic photolysis of caged neurotransmitters.
AB  - Stimulation of light-sensitive chemical probes has become a powerful tool for the
      study of dynamic signaLing processes in living tissue. Classically, this approach
      has been constrained by limitations of lens-based and point-scanning illumination
      systems. Here we describe a microscope configuration that incorporates a nematic
      liquid-crystal spatial light modulator to generate holographic patterns of
      illumination. This microscope can produce illumination spots of variable size and
      number, and in patterns shaped to precisely match user-defined elements in a
      specimen. Using holographic illumination to photolyze caged glutamate in brain
      slices, we show that shaped excitation on segments of neuronal dendrites and
      simultaneous, multispot excitation of different dendrites enables precise spatial
      and rapid temporal control of glutamate receptor activation. By allowing the
      excitation volume shape to be tailored precisely, the holographic microscope
      provides an extremely flexible method for activation of various photosensitive
      proteins and small molecules.

PMID- 19160518
TI  - Genome-wide analysis of transcription factor binding sites based on ChIP-Seq
      data.
AB  - Molecular interactions between protein complexes and DNA mediate essential gene
      regulatory functions. Uncovering such interactions by chromatin
      immunoprecipitation coupled with massively parallel sequencing (ChIP-Seq) has
      recently become the focus of intense interest. We here introduce quantitative
      enrichment of sequence tags (QuEST), a powerful statistical framework based on
      the kernel density estimation approach, which uses ChIP-Seq data to determine
      positions where protein complexes contact DNA. Using QuEST, we discovered several
      thousand binding sites for the human transcription factors SRF, GABP and NRSF at
      an average resolution of about 20 base pairs. MEME motif-discovery tool-based
      analyses of the QuEST-identified sequences revealed DNA binding by cofactors of
      SRF, providing evidence that cofactor binding specificity can be obtained from
      ChIP-Seq data. By combining QuEST analyses with Gene Ontology (GO) annotations
      and expression data, we illustrate how general functions of transcription factors
      can be inferred.

PMID- 19160519
TI  - Imaging dynamic cell-cell junctional coupling in vivo using Trojan-LAMP.
AB  - To study the physiological regulation and function of cell-cell gap junction
      communication in vivo, we developed a bioconjugate of caged dye, named dextran
      CANPE-HCC, for imaging cell coupling in small model organisms. In vitro, the
      compound was photolyzed efficiently with robust fluorescence enhancement. Dextran
      CANPE-HCC delivered into Caenorhabditis elegans oocytes was retained in cells
      throughout development. Using local uncaging, we photolyzed dextran-CANPE-HCC to
      release the small HCC dye and imaged the dynamics of intercellular dye transfer
      through gap junction channels, a technique we named Trojan-local activation of
      molecular fluorescent probes (LAMP). Early during embryonic development, the
      pattern of cell coupling undergoes dramatic remodeling and imaging revealed that
      the germ cell precursors, P2, P3 and P4, were isolated from the somatic cell
      communication compartment. As dextran-CANPE-HCC is chemically and metabolically
      stable, Labeled worms showed very bright signal upon photoactivation after
      hatching, which allowed us to examine cell coupling in living worms
      noninvasively.

PMID- 19160520
TI  - A-94964, a novel inhibitor of bacterial translocase I, produced by Streptomyces
      sp. SANK 60404. I. Taxonomy, isolation and biological activity.
AB  - Bacterial phospho-N-acetylmuramyl-pentapeptide translocase (translocase I: EC
      2.7.8.13) is a key enzyme in peptidoglycan biosynthesis, and a known target of
      antibiotics. Here we report a novel nucleoside inhibitor against translocase I, A
      94964, isolated from the culture broth of the strain Streptomyces sp. SANK 60404.
      A-94964 inhibited bacterial translocase I with IC50 value of 1.1 microg/ml, and
      showed antimicrobial activities against Staphylococcus aureus and Enterococcus
      faecalis with MIC of 100 and 50 microg/ml, respectively. A-94964 did not show
      cytotoxicity against mammalian cell lines.

PMID- 19160521
TI  - A-94964, novel inhibitor of bacterial translocase I, produced by Streptomyces sp.
      SANK 60404. II. Physico-chemical properties and structure elucidation.
AB  - In our screening for translocase I inhibitors, we found the novel nucleoside
      antibiotic, A-94964 in the culture broth of Streptomyces sp. SANK 60404. The
      structure of A-94964 was elucidated primarily by various NMR studies, including a
      1H-31P HMBC experiment. A-94964 has a unique structure which possesses a
      nucleoside moiety and an N-acylglucosamine moiety connected via a phosphate.

PMID- 19160522
TI  - Citrinamides, new potentiators of antifungal miconazole activity, produced by
      Penicillium sp. FKI-1938.
AB  - Two new aromatic alkaloids, designated citrinamides A and B, were isolated from
      the culture broth of Penicillium sp. FKI-1938 by solvent extraction, silica gel
      column chromatography and HPLC. Their structures were elucidated by spectroscopic
      analysis, including NMR and amino acid analysis. Citrinamides A and B showed
      moderate potentiation of miconazole activity against Candida albicans.

PMID- 19160523
TI  - Six new induced sesquiterpenes from the cultures of ascomycete Daldinia
      concentrica.
AB  - Six new sesquiterpenes having the botryane carbon skeleton (1-6), together with
      known compounds (7-10) were induced and isolated from the ascomycete Daldinia
      concentrica (strain S 0318). Structures elucidation was accomplished by NMR
      spectroscopic and X-ray crystallographic studies.

PMID- 19160524
TI  - Sterelactones: new isolactarane type sesquiterpenoids with antifungal activity
      from Stereum sp. IBWF 01060.
AB  - Four members of a new family of tetracyclic sesquiterenoids possessing the
      isolactarane skeleton have been isolated from mycelial cultures of Stereum sp.
      IBWF 01060. Their structure elucidation and their antifungal activity against
      several plant pathogens as well as other microorganisms are reported.

PMID- 19160525
TI  - Selective inhibition of acyl-CoA:cholesterol acyltransferase 2 isozyme by
      flavasperone and sterigmatocystin from Aspergillus species.
AB  - Five known fungal metabolites, aurasperone A, aurasperone D, averufanin,
      flavasperone and sterigmatocystin, were isolated from the culture broths of
      Aspergillus species as inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT)
      in the cell-based assay using ACAT1- and ACAT2-expressing CHO cells. These
      compounds share a similar polycyclic skeleton. Among them, flavasperone and
      sterigmatocystin, having an angular skeleton, showed selective inhibition toward
      ACAT2 isozyme, while the others having a linear one had no selectivity in
      inhibition.

PMID- 19160526
TI  - A new antioxidant, clitocybin A, from the culture broth of Clitocybe aurantiaca.
AB  - Clitocybin A (1), a new antioxidant, was isolated from the culture broth of
      Clitocybe aurantiaca. This compound was purified by solvent extraction, silica
      gel column chromatography, Sephadex LH-20 column chromatography and preparative
      HPLC. Its structure was determined as 4,6-dihydroxy-2-p-hydroxyphenyl-isoindol1
      one on the basis of the UV, NMR, and MS spectroscopic analysis. The compound 1
      showed potent free radical scavenging activity against superoxide, ABTS, and DPPH
      radicals, and protective effect against cellular DNA damage induced by oxidative
      stress.

PMID- 19160527
TI  - A new type of tripropeptin with anteiso-branched chain fatty acid from Lysobacter
      sp. BMK333-48F3.
AB  - Branched chain amino acids are often utilized as the precursors of many lipid
      containing bacterial secondary metabolites. The effect of isoleucine on the
      composition of the mixture of cyclic lipopeptide antibiotics, tripropeptins from
      Lysobacter sp. BMK333-48F3 was evaluated. As expected, a novel tripropeptin
      analog with an anteiso-branched fatty acid was produced. The new compound, TPPaiC
      shows potent antibacterial activity against Gram-positive bacteria including MRSA
      and VRE. On the other hand, no increase was observed in the production of other
      tripropeptins by the addition of isoleucine.

PMID- 19160528
TI  - Does the renin-angiotensin system also regulate intra-ocular pressure?
AB  - The renin-angiotensin-aldosterone system is known to play an essential role in
      controlling sodium balance and body fluid volumes, and thus blood pressure. In
      addition to the circulating system which regulates urgent cardiovascular
      responses, a tissue-localized renin-angiotensin system (RAS) regulates long-term
      changes in various organs. Many recognized RAS components have also been
      identified in the human eye. The highly vasoconstrictive angiotensin II (Ang II)
      is considered the key peptide in the circulatory RAS. However, the ultimate
      effect of RAS activation at tissue level is more complex, being based not only on
      the biological activity of Ang II but also on the activities of other products of
      angiotensinogen metabolism, often exerting opposite effects to Ang II action. In
      recent studies, orally administered angiotensin II type 1 receptor blockers and
      angiotensin-converting enzyme inhibitors lower intra-ocular pressure (IOP),
      likewise topical application of these compounds, the effect being more prominent
      in ocular hypertensive eyes. Based on previous findings and our own experimental
      data, it can strongly be suggested that the RAS not only regulates blood pressure
      but is also involved in the regulation of IOP.

PMID- 19160529
TI  - Lipoprotein predictors of cardiovascular events in statin-treated patients with
      coronary heart disease. Insights from the Incremental Decrease In End-points
      Through Aggressive Lipid-lowering Trial (IDEAL).
AB  - BACKGROUND: Few studies have looked into the ability of measurements of
      apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1) or apoB/apoA-1 to predict
      new coronary heart disease (CHD) events in patients with CHD on statin treatment.
      AIMS: In the IDEAL trial, to compare lipoprotein components to predict CHD events
      and to what degree differences in those parameters could explain the observed
      outcome. METHODS: We compared the ability of treatment with atorvastatin 80
      mg/day to that of simvastatin 20-40 mg/day to prevent CHD events in patients with
      CHD and used Cox regression models to study the relationships between on
      treatment levels of lipoprotein components to subsequent major coronary events
      (MCE). FINDINGS: Variables related to low-density lipoprotein cholesterol (LDL-C)
      carried more predictive information than those related to high-density
      lipoprotein cholesterol (HDL-C), but LDL-C was less predictive than both non-HDL
      C and apoB. The ratio of apoB to apoA-1 was most strongly related to MCE.
      However, for estimating differences in relative risk reduction between the
      treatment groups, apoB and non-HDL-C were the strongest predictors.
      INTERPRETATION: The on-treatment level of apoB/apoA-1 was the strongest predictor
      of MCE in the pooled patient population, whereas apoB and non-HDL-C were best
      able to explain the difference in outcome between treatment groups. Measurements
      of apoB and apoA-1 should be more widely available for routine clinical
      assessments.

PMID- 19160530
TI  - Elevated angiogenin levels in chronic heart failure.
AB  - BACKGROUND: Abnormal indices of angiogenesis have been reported in chronic heart
      failure (CHF). We tested the hypothesis that circulating angiogenin (a potent
      inducer of neovascularization in vivo) is higher in CHF patients compared with
      controls and associated with indices of CHF severity: brain natriuretic peptide
      (BNP), Simpson's left ventricular ejection fraction (EF), and New York Heart
      Association (NYHA) class. METHODS: Using a cross-sectional approach, we measured
      serum angiogenin and BNP levels in 109 consecutive patients with CHF (85 males;
      mean age 60 (standard deviation (SD) 10 yrs) and 112 asymptomatic controls with
      normal cardiac function and related levels to echocardiographic parameters.
      RESULTS: Angiogenin was significantly higher in CHF patients compared to controls
      (P < 0.001). On univariate analysis, angiogenin was positively associated with
      age, plasma glucose, insulin, and BNP (all P < 0.001); and negatively correlated
      with diastolic blood pressure (P = 0.04) and EF (P = 0.002). Angiogenin levels
      increased in an ordinal fashion with NYHA class, exaggerated by the presence of
      diabetes mellitus (pseudo R2 = 0.15, P < 0.001). In multivariate analysis,
      angiogenin levels were only associated with deteriorating NYHA classification
      (beta = 0.14 (95% confidence interval (CI) 0.09-0.19), P < 0.001). Angiogenin was
      also a modest discriminator for the presence of CHF (area under the curve 0.72;
      95% CI 0.62-0.82), P < 0.001). CONCLUSION: Angiogenin is related to worsening
      heart failure severity (NYHA classification), with the highest levels in NYHA
      class III. Further research is warranted to determine the validity of angiogenin
      in a diagnostic and prognostic capacity in CHF.

PMID- 19160531
TI  - Prescription refills and healthcare costs associated with topical metronidazole
      in Medicaid enrolled patients with rosacea.
AB  - BACKGROUND: Refill adherence to medications and healthcare costs are important
      factors to consider while making informed decisions regarding the treatment of
      rosacea patients. OBJECTIVE: The objective of this study was to examine
      predictors of number of refills related to topical metronidazole and total
      healthcare costs in rosacea patients. METHODS: This study utilized a longitudinal
      cohort design and followed rosacea patients enrolled in North Carolina Medicaid
      and who were prescribed at least one study medication (topical metronidazole,
      adapalene, azelaic acid, permethrin, and sulfacetamide). Patients' demographic
      characteristics, number of metronidazole refills, and different components of
      healthcare costs were examined. RESULTS: Out of the total 2587 rosacea patients,
      the majority (approximately 69%, n=1771) had one or more prescriptions for
      topical metronidazole. Most of the patients in this study were white (73%). After
      controlling for other variables, increasing age was associated with a higher
      number of metronidazole refills and healthcare costs (both p<0.001). Compared
      with white patients, African American patients had a significantly lower number
      of metronidazole refills (p<0.001). Compared with white patients, African
      American patients and 'other' races were associated with an 8.6% and 10.3%
      decrease in total healthcare costs respectively (both p<0.001). An increase in
      the number of metronidazole refills was not associated with an increase in
      healthcare costs. CONCLUSION: Patients' race is significantly associated with the
      number of topical metronidazole refills. Patients' healthcare costs increased
      with increasing age and charges paid for prescriptions. Topical metronidazole
      seems to be an economically feasible treatment option for Medicaid-enrolled
      patients with rosacea.

PMID- 19160532
TI  - Pimecrolimus 1% cream for pruritus in postmenopausal diabetic women with vulvar
      lichen simplex chronicus: a prospective non-controlled case series.
AB  - BACKGROUND: Pruritus vulvae may have a variety of causes, such as infections,
      dermatologic disorders or non-neoplastic/neoplastic vulvar diseases. OBJECTIVES:
      To investigate the efficacy and side effects of topical pimecrolimus 1% cream for
      pruritus vulvae. METHODS: Twelve postmenopausal diabetic women with vulvar lichen
      simplex chronicus were enrolled in this trial. Each patient was treated with
      pimecrolimus 1% cream which was applied twice daily in a thin layer to the vulvae
      for 3 months. Clinical examination and recording of patients' symptoms using a
      scoring system was performed by the same physician before, after 4 weeks and
      after 3 months of therapy. RESULTS: All of the patients completed the study. A
      substantial decrease in pruritus after treatment was reported by the patients at
      the 4th week (2.17+/-0.72, p<0.01) and 3rd month of treatment (0.42+/-0.92,
      p<0.001) when compared with the baseline score (3.75+/-0.45). Follow-up of the
      patients after 3 months of treatment showed that complete cure occurred in 10
      patients (83.3%) and the pruritus was improved in two (16.7%) patients.
      CONCLUSIONS: Pimecrolimus 1% cream seems to be an effective and safe treatment
      modality for pruritus in postmenopausal women with vulvar lichen simplex
      chronicus.

PMID- 19160533
TI  - Supplementation with Eskimo Skin Care improves skin elasticity in women. A pilot
      study.
AB  - OBJECTIVE: To investigate the question of whether supplementation with an oral
      oil formulation rich in natural stable fish oil can alter skin elasticity,
      transepidermal water loss (TEWL), and skin roughness in healthy women. METHODS:
      Twenty-four healthy women aged 40-60 years participated in a single-blind
      randomized trial for testing the effect of a proprietary oral supplement for skin
      nutrition (Eskimo Skin Care) on skin elasticity, TEWL, and skin roughness. Skin
      elasticity was measured by an optical cutometer, TEWL by a water-loss module
      based upon the vapour gradient principle, and skin roughness with a three
      dimensional microtopography imaging system. RESULTS: Skin elasticity increased by
      10% after 3 months of treatment with the supplement, a statistically significant
      increase in comparison with the control group (p=0.0298). There was a trend,
      though not statistically significant, towards a positive influence on the skin's
      barrier function. No effect on the skin roughness was observed. CONCLUSION:
      Eskimo Skin Care, an oral preparation rich in natural stable fish oil, can
      improve skin elasticity.

PMID- 19160534
TI  - Good clinical response to anti-psoriatic treatment with adalimumab and
      methotrexate does not inflict a direct effect on compartmentalization of T-cell
      subsets: a pilot study.
AB  - OBJECTIVES: The most recently introduced therapeutics for psoriasis are
      biologicals which can target the T-cell-mediated pathology of psoriasis in a
      direct or indirect manner. The present pilot study focuses on and compares the
      effect of a conventional systemic agent (methotrexate; MTX) with the effect of a
      TNF-binding biological (adalimumab) on psoriasis-associated T-cell subsets in
      peripheral blood (PB) and lesional skin. Insight is provided in the hypothesized
      compartmentalization of these T-cell subsets between PB and the cutaneous
      compartment. METHODS: Immunohistochemical stainings of designated T-cell subsets
      on psoriatic skin sections were performed and similar subsets were isolated from
      PB specimens by flow cytometry. These counts were correlated with clinical
      severity. RESULTS: Results showed that adalimumab had a greater clinical effect
      than MTX treatment after 12 weeks. In the dermis, only the CD3+ T cells were
      significantly reduced after 12 weeks of adalimumab therapy, whereas for MTX only
      CD3+ T cells in the epidermis and CD45RO+ T cells in the dermis reduced
      significantly. However, PB T-lymphocyte populations did not show significant
      shifts in quantification of T-cell subsets. CONCLUSION: Therefore,
      recompartmentalization of psoriasis-associated T-cell subsets between PB and
      lesional skin was not induced in this study as a therapeutic principle.
      Consequently, recompartmentalization of T-cell subsets does not seem an
      obligatory event in order to achieve good clinical response.

PMID- 19160535
TI  - A simple method to treat an ingrowing toenail with a shape-memory alloy device.
AB  - An ingrowing toenail has no definitive treatment. Previously, effective methods
      were complicated but easy ones had less effect. We show both an easy and an
      effective way with Cu-Al-Mn-based shape-memory alloys (SMAs). They have a
      characteristic shape which patients themselves can detach easily without any
      pain. But they also have enough corrective force. Cu-based SMAs cost much less
      than Ni-Ti-based alloys. Despite not being appropriate for all cases of ingrowing
      toenails, it is an easy, effective and less costly alternative.

PMID- 19160536
TI  - Bowen's disease treated by carbon dioxide laser. A series of 44 patients.
AB  - BACKGROUND: Bowen's disease is a common form of intraepidermal (in situ) squamous
      cell carcinoma of the skin and mucous membrane. Treatment with destruction of the
      epidermis by any method is necessary to prevent invasive squamous cell carcinoma.
      OBJECTIVE: To report our experience with CO2 laser vaporization in the treatment
      of Bowen's disease and try to identify which factors could have any influence on
      results. METHODS: A total of 44 patients were treated with the CO2 laser in
      superpulsed mode, focalized at 2 W/cm2. RESULTS: In 86.3% of patients, a unique
      treatment session was required. 'Clearance after one treatment' was achieved in
      86.3% of the total series of patients and only 7.9% of these patients developed
      recurrence of the lesion. In 11.3% of the cases, there was 'clearance after more
      than one treatment' without clinical recurrences in any of these patients during
      the follow-up. 'No response' was achieved in 2.2% of the total series of
      patients. CONCLUSION: We conclude that the CO2 laser in superpulsed mode is an
      effective, efficient, safe, functional and good cosmetics treatment for Bowen's
      disease and it provides the same recurrence rate as other more aggressive or more
      expensive modalities of treatment.

PMID- 19160537
TI  - Histologic evidence of new collagen formation using a Q-switched Nd:YAG laser in
      periorbital rhytids.
AB  - OBJECTIVES: Non-ablative laser treatment has been used for improving dermal
      toning. Laser application to dermis causes new collagen formation in terms of
      wound healing. We aimed to study mainly histological changes in skin after the
      use of a Q-switched Nd:YAG laser in non-ablative treatment of wrinkles. METHODS:
      The laser was adjusted to a fluency of 7 J/cm2 with a spot size of 3 mm and a
      pulse rate of 10 Hz to treat periorbital wrinkled areas. None of the patients had
      received filling materials, botulinum toxin injections or any dermabrasion
      procedures. All laser sessions were held every 15 days for a total of six
      sessions and all patients were photographed before treatment and then 2 months
      after the last treatment. Histological examinations were performed before laser
      treatment and 1 month after the final treatment. RESULTS: Four of eight
      individuals showed clinical improvement. The histological proportion of collagen
      fibers was measured by using the Samba method. An increase in the mean optical
      densities (MOD) of collagen fibers compared with baselines was statistically
      significant in all patients (p<0.05). CONCLUSION: The 1064-nm Q-switched Nd:YAG
      lasers appear to be safe and efficient for non-ablative remodeling of periorbital
      wrinkles.

PMID- 19160538
TI  - An urticarial vasculitis case induced by glatiramer acetate.
AB  - Urticarial vasculitis (UV) is a disease characterized clinically by urticarial
      skin lesions and histologically by leukocytoclastic vasculitis caused by
      immunocomplex accumulation in post-capillary venules. Cases induced by various
      drugs such as cimetidine, diltiazem, potassium iodide, fluoxetine, and non
      steroid inflammatory drugs have been reported in the literature. A 48-year-old
      female who developed pruritus and rash on her body 3 months after starting
      glatiramer acetate (GA) treatment for multiple sclerosis was diagnosed with UV
      after clinical and histopathological examination. This report presents the first
      case in the literature of UV induced by GA.

PMID- 19160539
TI  - Onychomycosis caused by Fusarium sp in Sri Lanka: prevalence, clinical features
      and response to itraconazole pulse therapy in six cases.
AB  - OBJECTIVES: The aims of our study were to ascertain the proportion of Fusarium
      onychomycosis among patients with suspected onychomycosis, to record clinical
      features and to assess the efficacy of itraconazole pulse therapy in treatment.
      METHODS: Six patients with positive isolates of Fusarium sp were treated in an
      open, prospective manner with itraconazole: two pulses for fingernails and three
      pulses for toenails. Significant growth of Fusarium sp was considered when both
      microscopy of direct mounts in KOH and culture were positive for mold. Efficacy
      parameters were mycological cure and clinical cure. Mycological cure was negative
      direct microscopy (KOH) and culture. Clinical cure was complete absence of signs
      of onychomycosis. RESULTS: Prevalence of Fusarium onychomycosis was 6.25%
      (8/128). Three women and three men were studied. All had bilateral big toenails
      involved which were of the distal and lateral onychomycosis. Three of them had
      associated fingernail onychomycosis with periungual inflammation. All our
      patients were immunocompetent. At month 12 from the start of treatment,
      mycological cure was 100% while only three out of five patients showed normal
      nail growth and clinical cure. There were no significant clinical or laboratory
      adverse effects. CONCLUSIONS: Our data reconfirmed that Fusarium nail infections
      are difficult to eradicate. Since the therapeutic reservoir in toenails is 11
      months, these patients should be followed up for a total of 12 months before
      coming to the final conclusion.

PMID- 19160540
TI  - The IKK-related kinases: from innate immunity to oncogenesis.
AB  - Over the past four years, the field of the innate immune response has been highly
      influenced by the discovery of the IkappaB kinase (IKK)-related kinases, TANK
      Binding Kinase 1 (TBK1) and IKKi, which regulate the activity of interferon
      regulatory factor (IRF)-3/IRF-7 and NF-kappaB transcription factors. More
      recently, additional essential components of the signaling pathways that activate
      these IKK homologues have been discovered. These include the RNA helicases RIGi
      and MDA5, and the downstream mitochondrial effector known as CARDIF/MAVS/VISA/IPS
      1. In addition to their essential functions in controlling the innate immune
      response, recent studies have highlighted a role of these kinases in cell
      proliferation and oncogenesis. The canonical IKKs are well recognized to be a
      bridge linking chronic inflammation to cancer. New findings now suggest that the
      IKK-related kinases TBK1 and IKKi also participate in signaling pathways that
      impact on cell transformation and tumor progression. This review will therefore
      summarize and discuss the role of TBK1 and IKKi in cellular transformation and
      oncogenesis by focusing on their regulation and substrate specificity.

PMID- 19160541
TI  - Repression of interferon-gamma expression in T cells by Prospero-related homeobox
      protein.
AB  - Interferon-gamma (IFN-gamma) is a major proinflammatory effector and regulatory
      cytokine produced by activated T cells and NK cells. IFN-gamma has been shown to
      play pivotal roles in fundamental immunological processes such as inflammatory
      reactions, cell-mediated immunity and autoimmunity. A variety of human disorders
      have now been linked to irregular IFN-gamma expression. In order to achieve
      proper IFN-gamma-mediated immunological effects, IFN-gamma expression in T cells
      is subject to both positive and negative regulation. In this study, we report for
      the first time the negative regulation of IFN-gamma expression by Prospero
      related Homeobox (Prox1). In Jurkat T cells and primary human CD4+ T cells, Prox1
      expression decreases quickly upon T cell activation, concurrent with a dramatic
      increase in IFN-gamma expression. Reporter analysis and chromatin
      immunoprecipitation (ChIP) revealed that Prox1 associates with and inhibits the
      transcription activity of IFN-,gammapromoter in activated Jurkat T cells. Co
      immunoprecipitation and GST pull-down assay demonstrated a direct binding between
      Prox1 and the nuclear receptor peroxisome proliferator-activated receptor gamma
      (PPPARgamma, which is also an IFN-gamma repressor in T cells. By introducing
      deletions and mutations into Prox1, we show that the repression of IFN-gamma
      promoter by Prox1 is largely dependent upon the physical interaction between
      Prox1 and PPPARgamma Furthermore, PPPARgammaantagonist treatment removes Prox1
      from IFN-gamma promoter and attenuates repression of IFN-gamma expression by
      Prox1. These findings establish Prox1 as a new negative regulator of IFN-gamma
      expression in T cells and will aid in the understanding of IFN-gamma
      transcription regulation mechanisms.

PMID- 19160542
TI  - Heterotrimeric G-protein is involved in phytochrome A-mediated cell death of
      Arabidopsis hypocotyls.
AB  - The heterotrimeric guanine nucleotide-binding protein (G-protein) has been
      demonstrated to mediate various signaling pathways in plants. However, its role
      in phytochrome A (phyA) signaling remains elusive. In this study, we discover a
      new phyA-mediated phenotype designated far-red irradiation (FR) preconditioned
      cell death, which occurs only in the hypocotyls of FR-grown seedlings following
      exposure to white light (WL). The cell death is mitigated in the Ga mutant gpa1
      but aggravated in the Gbeta mutant agb1 in comparison with the wild type (WT),
      indicative of antagonistic roles of GPA1 and AGB1 in the phyA-mediated cell-death
      pathway. Further investigation indicates that FR-induced accumulation of
      nonphotoconvertible protochlorophyllide (Pchlide633), which generates reactive
      oxygen species (ROS) on exposure to WL, is required for FR-preconditioned cell
      death. Moreover, ROS is mainly detected in chloroplasts using the fluorescent
      probe. Interestingly, the application of H2O2 to dark-grown seedlings results in
      a phenotype similar to FR-preconditioned cell death. This reveals that ROS is a
      critical mediator for the cell death. In addition, we observe that agb1 is more
      sensitive to H2O2 than WT seedlings, indicating that the G-protein may also
      modify the sensitivity of the seedlings to ROS stress. Taking these results
      together, we infer that the G-protein may be involved in the phyA signaling
      pathway to regulate FR-preconditioned cell death of Arabidopsis hypocotyls. A
      possible mechanism underlying the involvement of the G-protein in phyA signaling
      is discussed in this study.

PMID- 19160543
TI  - HIV-1 Vpr-induced cell death in Schizosaccharomyces pombe is reminiscent of
      apoptosis.
AB  - Human immunodeficiency virus type 1 (HIV-1) Vpr induces cell death in mammalian
      and fission yeast cells, suggesting that Vpr may affect a conserved cellular
      process. It is unclear, however, whether Vpr-induced yeast cell death mimics Vpr
      mediated apoptosis in mammalian cells. We have recently identified a number of
      Vpr suppressors that not only suppress Vpr-induced cell death in fission yeast,
      but also block Vpr-induced apoptosis in mammalian cells. These findings suggest
      that Vpr-induced cell death in yeast may resemble some of the apoptotic processes
      of mammalian cells. The goal of this study was to develop and validate a fission
      yeast model system for future studies of apoptosis. Similar to Vpr-induced
      apoptosis in mammalian cells, we show here that Vpr in fission yeast promotes
      phosphatidylserine externalization and induces hyperpolarization of mitochondria,
      leading to changes of mitochondrial membrane potential. Moreover, Vpr triggers
      production of reactive oxygen species (ROS), indicating that the apoptotic-like
      cell death might be mediated by ROS. Interestingly, Vpr induces unique
      morphologic changes in mitochondria that may provide a simple marker for
      measuring the apoptotic-like process in fission yeast. To verify this
      possibility, we tested two Vpr suppressors (EF2 and Hsp16) that suppress Vpr
      induced apoptosis in mammalian cells in addition to a newly identified Vpr
      suppressor (Skp1). All three proteins abolished cell death mediated by Vpr and
      restored normal mitochondrial morphology in the yeast cells. In conclusion, Vpr
      induced cell death in fission yeast resembles the mammalian apoptotic process.
      Fission yeast may thus potentially be used as a simple model organism for the
      future study of the apoptotic-like process induced by Vpr and other proapoptotic
      agents.

PMID- 19160544
TI  - Protein phosphatase PP4 is overexpressed in human breast and lung tumors.

PMID- 19160546
TI  - Where Freud and the oyster converge.

PMID- 19160545
TI  - Dopamine neuron degeneration induced by MPP+ is independent of CED-4 pathway in
      Caenorhabditis elegans.

PMID- 19160547
TI  - ["Nurses exert an essential role in the diffusion of palliative culture"].

PMID- 19160548
TI  - Exercise and reduce heart disease risk.

PMID- 19160549
TI  - Western diet and heart disease.

PMID- 19160550
TI  - How cardiovascular risk factors may be linked to poorer mental ability.

PMID- 19160551
TI  - Unhealthy behaviors lead to chronic disease in those 50 years of age and older.

PMID- 19160552
TI  - The impact of Alzheimer's disease medication on muscle relaxants.

PMID- 19160553
TI  - Murphy's eye: go for the eye: learning fibreoptic intubation.

PMID- 19160554
TI  - Point-of-care device: a word of caution.

PMID- 19160555
TI  - Child health nurses also forgotten?

PMID- 19160556
TI  - Dying with dignity.

PMID- 19160557
TI  - Praise for psych nurses.

PMID- 19160558
TI  - Caring for patients with Parkinson's disease.

PMID- 19160562
TI  - Obstructive sleep apnoea and breathing retraining.

PMID- 19160563
TI  - Rostering patterns cause shortage.

PMID- 19160564
TI  - Dangerous driving.

PMID- 19160566
TI  - Learn from mistakes.

PMID- 19160568
TI  - A novel physical and functional association between nucleoside  diphosphate
      kinase A and AMP-activated protein kinase alpha1 in  liver and lung.

PMID- 19160567
TI  - Studying addiction in the age of neuroimaging. Marian W. Fischman Lecture given
      at the 2008 meeting of CPDD.

PMID- 19160569
TI  - Retraction notice to "Solubilization of DNAPLs by mixed surfactant: synergism and
      solubilization capacity" [J. Hazard. Mater. B136 (2006) 513-159].

PMID- 19160570
TI  - Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens and regulation
      of the response to hypoxia, and their roles as treatment targets.
AB  - Prolyl 4-hydroxylases (P4Hs) have central roles in the synthesis of collagens and
      the regulation of oxygen homeostasis. The 4-hydroxyproline residues generated by
      the endoplasmic reticulum (ER) luminal collagen P4Hs (C-P4Hs) are essential for
      the stability of the collagen triple helix. Vertebrate C-P4Hs are alpha2beta2
      tetramers with three isoenzymes differing in their catalytic alpha subunits.
      Another P4H family, the HIF-P4Hs, hydroxylates specific prolines in the alpha
      subunit of the hypoxia-inducible transcription factor (HIF), a master regulator
      of hypoxia-inducible genes, and controls its stability in an oxygen-dependent
      manner. The HIF-P4Hs are cytoplasmic and nuclear enzymes, likewise with three
      isoenzymes in vertebrates. A third vertebrate P4H type is an ER transmembrane
      protein that can act on HIF-alpha but not on collagens. All P4Hs require Fe2+, 2
      oxoglutarate, O2, and ascorbate. C-P4Hs are regarded as attractive targets for
      pharmacological inhibition to control excessive collagen accumulation in fibrotic
      diseases and severe scarring, while HIF-P4H inhibitors are believed to have
      beneficial effects in the treatment of diseases such as myocardial infarction,
      stroke, peripheral vascular disease, diabetes, and severe anemias. Studies with
      P4H inhibitors in various animal models of fibrosis, anemia, and ischemia and
      ongoing clinical trials with HIF-P4H inhibitors support this hypothesis by
      demonstrating efficacy in many applications.

PMID- 19160571
TI  - Interactions between ghrelin, leptin and IGF-I affect metabolic syndrome and
      early atherosclerosis.
AB  - BACKGROUND: High leptin and low ghrelin are associated with the metabolic
      syndrome (MS). AIMS AND METHODS: Ghrelin, leptin (RIA kits), and insulin-like
      growth factor I (IGF-I) (ELISA kit) concentrations of the population-based cohort
      of 1045 subjects and their interactions with metabolic parameters were analysed.
      Intima-media thickness (IMT) was measured with carotid ultrasound. RESULTS: The
      interaction between leptin and ghrelin on the MS was significant (P = 0.011). An
      additive effect of high leptin and low ghrelin on metabolic disturbances was
      observed: low ghrelin concentration (adjusted for age and sex) (P < 0.001) was
      associated with the MS and type 2 diabetes in the highest but not in the lower
      leptin quartiles. In the highest leptin quartile, ghrelin concentrations
      decreased linearly when the number of International Diabetes Federation MS
      criteria met (P < 0.01) increased. Ghrelin-leptin relation was independently
      associated with carotid IMT (P < 0.005). The independent positive association (P
      < 0.01) between the plasma ghrelin quartile and the carotid IMT was evident in
      the lowest IGF-I quartile. CONCLUSIONS: Low ghrelin is associated with MS and
      type 2 diabetes in the presence of insulin and leptin resistance. Ghrelin-leptin
      relation is associated with early atherosclerosis. The interaction between IGF-I
      and ghrelin modifies the association of ghrelin with early atherosclerosis.

PMID- 19160572
TI  - New insights into central control mechanisms of circulation. Proceedings of a
      satellite symposium of the 5th Congress of the International Society for
      Autonomic Neuroscience (ISAN 2007) Wakayama City, Japan, October 3rd 2007.

PMID- 19160574
TI  - [Hospital infections by specific pathogens and their management. 3. Pseudomonas
      aeruginosa].

PMID- 19160573
TI  - Prescribing during pregnancy.  Prenatal drug exposure and an untreated
      psychiatric disorder both present risks.

PMID- 19160575
TI  - [Effect of tribendimidine, artesunate, artemether and praziquantel, administered
      intragastrically at single, multiple or combined doses, to rats infected with
      Clonorchis sinensis].
AB  - OBJECTIVE: To assess the efficacy of single, multiple or combined oral doses of
      tribendimidine, artesunate, artemether and praziquantel against Clonorchis
      sinensis in rats. METHODS: A total of 147 rats, each infected with 50 C. sinensis
      metacercariae, were used in experimental chemotherapy. All the drugs used were
      administered intragastrically 42-44 d after infection. (1) Sixty infected rats
      were randomly divided into 11 groups (4-5 rats per group) and the following drug
      dose-schedules were applied, i.e. under the same total dose tribendimidine or
      praziquantel was given at a single dose of 150 mg/kg, or given at smaller divided
      doses of 75 mg/kg (qd for 2 d), 50 mg/kg (qd for 3 d), 25 mg/kg (tid for 2 d);
      artesunate or artemether was given at a single dose of 75 mg/kg, or given a half
      dose of 37.5 mg/kg daily for 2 days. (2) Eighty-seven infected rats were randomly
      divided into 15 groups (4-6 rats per group) for combined treatment with the
      following drug administration regimens, i.e. artesunate or artemether 30 mg/kg
      plus praziquantel 150 mg/kg or tribendimidine 50 mg/kg and 75 mg/kg,
      respectively; tribendimidine 50 mg/kg plus praziquantel 150 mg/kg; tribendimidine
      75 mg/kg plus praziquantel 187.5 mg/kg. A single dose of each drug mentioned
      above was also involved. Untreated C. sinensis-infected rats served as control.
      Rats were killed 14 days post-treatment, worms recovered from the bile duct and
      the liver tissue, mean worm burden reduction calculated and mean worm burden
      compared between the groups using non-parametric method (Mann-Whitney test).
      RESULTS: Rats infected with C. sinensis and treated at a single 150 mg/kg dose of
      either tribendimidine or praziquantel resulted in a worm reduction of 57.2% and
      63.8%, respectively. Whilst administration of tribendimidine at smaller but
      multiple doses given within 2-3 days at the same total dosage resulted in a
      slightly higher worm reduction (77.1%-79.4%), the opposite trend was observed for
      praziquantel (50.6%-54.2%). However, for both tribendimidine and praziquantel,
      the difference of mean worm burden lacked statistical significance between single
      and multiple doses. Infected rats administered either artesunate or artemether at
      a single dose of 75 mg/kg or a daily dose of 37.5 mg/kg for 2 days, the worm
      reduction was 100% and 90.4%-98.5%, respectively. Combined treatment with low
      doses of tribendimidine (50 mg/kg or 75 mg/kg) plus praziquantel (150 mg/kg or
      187.5 mg/kg) resulted in a worm reduction of 74.9%-100%, which were higher than
      those of 26.9%-79.6% obtained from a single dose of each drug used. High worm
      reduction of 74.4%-97.9% was also observed when administering a low dose of
      artesunate or artemether (30 mg/kg) plus a low dose of tribendimidine (50 mg/kg
      or 75 mg/kg) or praziquantel (150 mg/kg). Mean worm reduction of 24.8%-79.6% were
      seen when drugs used at single doses. CONCLUSION: The investigation confirmed
      that tribendimidine, artesunate, artemether-and praziquantel are all efficacious
      against C. sinensis, and that drug combination acts synergistically.

PMID- 19160576
TI  - [Hospital infections by specific pathogens and their management. 4. Enterococci].

PMID- 19160577
TI  - [Hospital infection by specific pathogens and their management. 5. Mycobacteria].

PMID- 19160578
TI  - [Hospital infections by specific pathogens and their management. 6. Hepatitis
      viruses].

PMID- 19160579
TI  - [Hospital infections by specific pathogens and their management. 7. HIV].

PMID- 19160580
TI  - [Hospital infections by specific pathogens and their management. 8. Influenza].

PMID- 19160581
TI  - [Management of specific patients in relation to the management of hospital
      infections. 1. Intra-tracheal intubation and tracheotomy].

PMID- 19160582
TI  - [Management of specific patients in view of hospital infection prevention. 2.
      Patients with venous catheters].

PMID- 19160583
TI  - [Management of specific patients in view of hospital infection management. 3.
      Patients with indwelling urinary catheters].

PMID- 19160584
TI  - [Management of specific patients in view of hospital infections. 4. Patients with
      decubitus ulcer].

PMID- 19160585
TI  - [Hospital infections: progress in their diagnosis, treatment and prevention.
      Discussion].

PMID- 19160586
TI  - [Current topics in echocardiography].

PMID- 19160587
TI  - [Changes in the guidelines for cardiopulmonary resuscitation].

PMID- 19160588
TI  - [Hepatitis C virus genotypes distribution and viral load level among HIV
      coinfected patients].

PMID- 19160589
TI  - ["Minimum knowledge" needed by primary care physicians. Blood pressure evaluation
      and instructions on salt-reducing diet for patients with hypertension and
      nutrition and exercise guidance for diabetic patients].

PMID- 19160590
TI  - [Comprehensive internal medicine specialists and subspecialties. The role of
      women physicians].

PMID- 19160591
TI  - [Basic knowledge in medical genetics for internists (1)].

PMID- 19160592
TI  - The effect of catechol-O-methyltransferase Met/Val functional polymorphism on
      smoking cessation: retrospective and prospective analyses in a cohort study.
AB  - OBJECTIVE: The Met/Val functional polymorphism of the gene-encoding catechol-O
      methyltransferase (COMT) is one of the most widely tested variants for
      association with different phenotypes of addictive behavior, but replication has
      been inconsistent for smoking status. We investigated the relationship of this
      COMT single nucleotide polymorphism with smoking cessation in elderly persons in
      retrospective and prospective analyses. METHODS: The study is embedded in the
      population-based Rotterdam Study cohort and included 5,115 persons aged 55 years
      and more. In the retrospective analyses using logistic regression, current
      smokers who had smoked 10 or more cigarettes daily for 10 or more years were
      compared with former smokers. In the prospective analyses, we followed 1,195
      current smokers up to 12 years and used Cox proportional hazard model to detect
      the effect of the COMT single nucleotide polymorphism on self-reported incidence
      of smoking cessation. RESULTS: The Val/Val genotype of COMT had a consistent
      association with smoking cessation as compared with the Met/Met+Met/Val genotypes
      in retrospective [odds ratio=0.79, 95% confidence interval (CI): 0.66-0.96,
      P=0.02] and prospective analyses (hazard ratio=0.80, 95% CI: 0.63-1.01, P=0.06).
      In the pooled analyses of prevalent and incident cessation cases that we compared
      with persisting smokers, the odds ratio was 0.70 (95% CI: 0.55-0.88, P=0.003). No
      sex difference and no effect of the COMT polymorphism on smoking initiation were
      observed. CONCLUSION: Our results suggest that COMT Met/Val polymorphism is
      strongly associated with smoking cessation. The Met allele is the risk allele
      that decreases the likelihood of smoking cessation in men and women.

PMID- 19160594
TI  - Perceptual organization and neural computation.

PMID- 19160595
TI  - An unusual guanyl oligonucleotide regulates cellulose synthesis in Acetobacter
      xylinum.
AB  - The mechanism of GTP-specific activation of the membrane-bound cellulose synthase
      system of Acetobacter xylinum has been further elucidated. The supernatant
      fraction derived from washed membranes of this organism contains an enzyme which
      reacts with GTP to form a low molecular mass, heat-stable compound,tentatively
      characterized as a cyclic oligonuleotide composed of GMP residues, which is the
      immediate activator of the cellulose synthase. This activation is reversed by a
      membrane-bound enzyme that degrades the activator; the latter enzyme is inhibited
      by Ca (2+). It is suggested that the interaction between these enzymes and
      nucleotide derivatives, mediated by Ca (2+), may regulate cellulose synthesis in
      VIVO.

PMID- 19160596
TI  - Pancreatic stone protein. What is it and what does it do?

PMID- 19160597
TI  - Differences of pancreatic stone morphology and content in patients with
      pancreatic lithiasis.
AB  - Pancreatic stones from 25 patients were compared by morphological and/or
      radiological examination. Twenty patients, mostly alcoholics, had calcified
      stones. Five (four nonalcoholic women) had radiolucent stones. Aspect and
      consistency of calcified stones varied from compact and resistant to coralliform
      and brittle but were identical in the same patient. In the coralliform type,
      organic fibrils with a diameter up to 10 microm and a length up to a few
      centimeters were observed, strongly attached to mineral crystals. The
      lithostathine (formerly called pancreatic stone protein, PSP) content was
      estimated in each stone significantly lower in the populations with larger stone
      mass, compared to populations with small amounts of stones. Transparent stones
      were built up of an amorphous material solubilized at acidic pH and corresponding
      to degraded forms of lithostathine-S (S for secretory). In one patient, we
      followed over seven years the evolution of a radiolucent calculus. We observed
      that the radiolucent core occurred first, and was secondarily wrapped in a
      calcified shell. We conclude that morphological differences observed in this
      study among pancreatic stones suggest that different mechanisms have been
      involved in their formation. Among them, lithostathine transformation into
      insoluble polypeptides may provide different types of protein aggregates, some of
      them being able to promote CaCO(3) apposition and others having no affinity for
      calcium.

PMID- 19160600
TI  - [The flow of Italian workers to the Lorraine iron district: spatial and
      demographic analysis, 1945-68].

PMID- 19160599
TI  - Clinical significance of chronic hyperamylasemia.
AB  - A longitudinal study of patients with persistent hyperamylasemia was carried out
      to evaluate the clinical significance of this condition. Twenty-five outpatients
      were studied by means of serum amylase, isoamylase (wheat germ-inhibition
      method), and lipase determination; macroamylase detection; and abdominal
      ultrasonography over a one-year period. Cellulose acetate electrophoresis was
      carried out to validate the wheat germ-inhibition tests; the results of the two
      assays were closely correlated, except in three patients with macroamylasemia. At
      the time of the study, none of the patients had evident signs or symptoms of
      pancreatic disease. At initial evaluation, wheat germ test demonstrated an
      elevation of only salivary isoamylase in 16 patients, both pancreatic and
      salivary isoenzyme in two, and only pancreatic isoamylase in six patients (three
      with macroamylasemia). Normal salivary and pancreatic isoenzymes were found in
      one with predominantly pancreatic isoamylase. At the 12-month follow-up,
      hyperamylasemia had disappeared in six cases and salivary isoamylase elevation in
      three; pancreatic isoamylase remained abnormally high in all eight patients in
      whom it was elevated at initial evaluation, and lipase was abnormally high in
      three patients with elevated pancreatic isoamylase. Of the five patients with
      true pancreatic hyperamylasemia, one had a juxtapapillary duodenal diverticulum,
      one showed a slight ultrasound alteration of the pancreas, and one had a past
      history of acute pancreatitis. In our study, most cases of chronic
      hyperamylasemia were of nonpancreatic origin. In the patients with elevated
      pancreatic isoamylase, there was no clinical evidence of pancreatic damage,
      although a subclinical pancreatic involvement could not be excluded in some.

PMID- 19160601
TI  - [Recruiting and screening migrants: the mission of the ONI in Milan as told by
      chief medical officer Deberdt, 1953-63].

PMID- 19160602
TI  - Effect of synthetic porcine neuropeptide Y (NPY) on splanchnic blood flows and
      exocrine pancreatic secretion in dogs.
AB  - This study examined the effect of synthetic porcine neuropeptide Y on the
      splanchnic blood flows and the exocrine pancreatic secretion in dogs. Graded
      doses of neuropeptide Y (0.1-5 microg/kg, intravenous) caused dose-dependent
      reduction of the secretin-stimulated exocrine pancreatic secretion and of the
      blood flows in the superior mesenteric artery, the portal vein, and the
      pancreatic tissue. Neuropeptide Y at 5 microg/kg reduced the blood flows to 45.9
      +/- 13.3% (superior mesenteric artery), 63.0 +/- 10.5% (portal vein), and 77.9 +/
      4.8% (pancreatic tissue), respectively. This dose also reduced secretin
      stimulated pancreatic juice volume and CCK-8 plus secretin-stimulated protein
      output to 65.2 +/- 9.3 and 63.3 +/- 14.0%, respectively. This study shows a
      potent vasoconstrictor effect of neuropeptide Y on splanchnic vessels.
      Neuropeptide Y also inhibited exocrine pancreatic secretion in a significant
      correlation with the reduction in pancreatic tissue blood flow, which suggests
      that reduction in the blood flow may be one of the possible mechanisms of the
      inhibitory action of neuropeptide Y on exocrine secretion.

PMID- 19160605
TI  - [The transformation of Italian rural families in France: collective and
      individual projects in the southwest in the post-World War II era].

PMID- 19160603
TI  - Prevalence of subtypes of intestinal metaplasia in gastric antral mucosa.
AB  - A prospective gastroscopic-bioptic study of 533 patients was performed to assess
      the prevalence and distribution of intestinal metaplasia (IM) and its subtypes in
      the antral mucosa of patients with various upper intestinal disorders and to
      assess whether the presence of certain IM subtypes might be of help in selecting
      patients for careful endoscopic-bioptic surveillance in the screening for gastric
      carcinoma. IM was found in 135 patients (25.3%). Its prevalence increased with
      age (P < 0.001) and was strongly associated with intestinal-type carcinoma as
      compared to diffuse-type carcinoma (P < 0.001), gastritis (P < 0.001), and
      gastric ulcer (P < 0.05). Type I IM was predominant (98.5%), whereas types II and
      III IM, respectively, were found in 77.8% and 15.6% of the patients with IM. No
      difference in the prevalence of type I and II IM was found among the various
      gastric disease states. Type III IM was strongly associated with intestinal-type
      carcinoma as compared to either benign lesions (P < 0.01) or diffuse-type
      carcinoma. These results suggest that type III IM may play a special role in the
      histogenesis of intestinal-type carcinoma and suggest that the finding of this IM
      subtype in gastric biopsies may possibly be of help in identifying patients at
      greater risk of developing carcinoma.

PMID- 19160606
TI  - [A short history of the reconceptualization of eugenics in contemporary China].

PMID- 19160607
TI  - [A first X-ray apparatus to arrive at Suzhou Boxi Hospital, 1897].

PMID- 19160608
TI  - RESPECT-Mil: feasibility of a systems-level collaborative care approach to
      depression and post-traumatic stress disorder in military primary care.
AB  - BACKGROUND: U.S. military ground forces report high rates of war-related
      traumatic stressors, posttraumatic stress disorder (PTSD), and depression
      following deployment in support of recent armed conflicts in Iraq and
      Afghanistan. Affected service members do not receive needed mental health
      services in most cases, and they frequently report stigma and significant
      structural barriers to mental health services. Improvements in primary care may
      help address these issues, and evidence supports the effectiveness of a systems
      level collaborative care approach. OBJECTIVE: To test the feasibility of systems
      level collaborative care for PTSD and depression in military primary care. We
      named our collaborative care model "Re-Engineering Systems of Primary Care for
      PTSD and Depression in the Military" (RESPECT-Mil). METHODS: Key elements of
      RESPECT-Mil care include universal primary care screening for PTSD and
      depression, brief standardized primary care diagnostic assessment for those who
      screen positive, and use of a nurse "care facilitator" to ensure continuity of
      care for those with unmet depression and PTSD treatment needs. The care
      facilitator assists primary care providers with follow-up, symptom monitoring,
      and treatment adjustment and enhances the primary care interface with specialty
      mental health services. We report assessments of feasibility of RESPECT-Mil
      implementation in a busy primary care clinic supporting Army units undergoing
      frequent Iraq, Afghanistan, and other deployments. RESULTS: Thirty primary care
      providers (family physicians, physician assistants, and nurse practitioners) were
      trained in the model and in the care of depression and PTSD. The clinic screened
      4,159 primary care active duty patient visits: 404 screens (9.7%) were positive
      for depression, PTSD, or both. Sixty-nine patients participated in collaborative
      care for 6 weeks or longer, and the majority of these patients experienced
      clinically important improvement in PTSD and depression. Even although RESPECT
      Mil participation was voluntary for providers, only one refused participation. No
      serious adverse events were noted. CONCLUSIONS: Collaborative care is an evidence
      based approach to improving the quality of primary care treatment of anxiety and
      depression. Our version of collaborative care for PTSD and depression, RESPECT
      Mil, is feasible, safe, and acceptable to military primary care providers and
      patients, and participating patients frequently showed clinical improvements.
      Efforts to implement and evaluate collaborative care approaches for mental
      disorders in populations at high risk for psychiatric complications of military
      service are warranted.

PMID- 19160609
TI  - Immunization against Haemophilus influenzae type B fails to prevent orbital and
      facial cellulitis: results of a 25-year study among military children.
AB  - Vaccines against Haemophilus influenzae type B (HI) and Streptococcus pneumoniae
      (SP) have dramatically reduced the incidence of bacterial meningitis (due to both
      HI and SP) and epiglottitis (due to HI) in childhood. The effects of these
      vaccines on other conditions, however, are less clear. We report an analysis of
      the effect of serial deployment of various HI and SP vaccines over a 25-year
      period, involving an examination of over half a million pediatric
      hospitalizations occurring in Army hospitals worldwide. We show that, in marked
      contrast to the reduction in the number of meningitis and epiglottitis cases, the
      disease burden of orbital and facial cellulitis--conditions oft attributed to HI
      and SP-did not diminish.

PMID- 19160610
TI  - The retrospective prevalence of community-acquired methicillin-resistant
      Staphylococcus aureus in soft tissue abscesses at two military level I trauma
      centers.
AB  - STUDY OBJECTIVE: Many studies have shown that community-acquired methicillin
      resistant Staphylococcus aureus (CAMRSA) is a very prevalent organism. However,
      no data have been published to date with regard to CAMRSA prevalence in patients
      presenting to the emergency department (ED) of a military medical facility. Our
      objective is to estimate the period prevalence of CAMRSA in cases of soft tissue
      abscesses seen in the emergency departments of two major military hospitals.
      METHODS: A retrospective review of electronic records was performed from January
      1, 2004 to August 10, 2005. This database was used to identify patients with the
      diagnosis of abscess, the procedure code for incision and drainage, and culture
      of wound. After data were accumulated, standard prevalence calculations were
      applied to determine prevalence of CAMRSA in abscesses at our emergency
      departments. Antibiotic susceptibilities were then evaluated with regard to the
      CAMRSA bacteria. RESULTS: The prevalence at our two emergency departments was 68%
      (751 abscesses, 220 cultured, 155 methicillin-resistant S. aureus (MRSA)-positive
      cultures). The prevalence at Brooke Army Medical Center and Wilford Hall Medical
      Center emergency departments was 70% (520 abscesses, 145 cultured, and 101 MRSA
      positive) and 65% (231 abscesses, 75 cultured, and 49 MRSA positive),
      respectively. CONCLUSION: The occurrence of CAMRSA is not isolated to the
      civilian population. The prevalence of CAMRSA in this population is significant,
      and may pose serious operational and deployment-related ramifications requiring
      the attention of military medical planners as well as forward medical care
      providers. The probability of CAMRSA infection should be considered when treating
      soft tissue abscesses in the military emergency department.

PMID- 19160611
TI  - Outbreak of sandfly fever in central Iraq, September 2007.
AB  - An outbreak of nonspecific febrile illnesses occurred among U.S. Army troops in
      September 2007 at a remote, newly established, rural-situated patrol base, south
      of Baghdad, Iraq. Soldiers displayed an acute flu-like syndrome with symptoms of
      fever, headache, malaise, and myalgia. A total of 14 cases was identified and
      treated presumptively as query fever. Subsequent convalescent serum specimens
      confirmed 13 (92.9%) positive for sandfly Sicilian virus and 3 (21.4%) positive
      for Coxiella burnetii, with two positive for both. One sandfly Sicilian virus
      case tested positive for Brucella spp. This outbreak emphasizes the potential for
      multiple simultaneous disease exposures to endemic diseases in nonindigenous
      military personnel at remote military locations in Iraq. Recommendations include
      increased theater disease surveillance, medical training, and vector control.

PMID- 19160612
TI  - Did you just ask if I would lead a humanitarian mission?
AB  - This article is intended to help guide personnel chosen to lead military
      humanitarian missions. Suggestions for various stages of mission planning and
      execution are provided.

PMID- 19160613
TI  - Military community: a privileged site for clinical research: Epidemiological
      Study of Metabolic Syndrome Risk Factors in the Military Environment.
AB  - The metabolic syndrome is considered to be an important public health problem.
      The Epidemiological Study of Metabolic Syndrome Risk Factors in the Military
      Environment is a prospective epidemiological study that is designed to identify
      clinical and laboratory parameters of metabolic syndrome and cardiovascular risk
      factors with an initial 1-year cross-sectional study followed by a 10-year follow
      up and patient care. One hundred eight-five (9%) of 2,045 military personnel
      subjects presented at least three of the five National Cholesterol Education
      Program Expert Panel on Detection, Evaluation and Treatment of High Blood
      Cholesterol in Adults (Adult Treatment Panel III) criteria. They were
      significantly older (42.2 +/- 8.5 years) than the other subjects (37.3 +/- 8.7
      years, p < 0.001), had a higher body mass index (BMI) (29.5 +/- 3.4 vs. 24.8 +/-
      2.9, p < 0.001), and a greater body weight at age 20 (75.4 +/- 11 vs. 70.4 +/-
      8.5 kg, p < 0.001). Smoking, little physical activity, and family histories of
      diabetes and arterial hypertension were more frequent in these subjects. Total
      plasma cholesterol and C-reactive protein were higher. Plasma insulin and BMI (r
      = 0.456, p < 0.0001) and plasma insulin and waist circumference (r = 0.446, p <
      0.0001) were well correlated. Plasma insulin and homeostasis model assessment
      increased with the number of metabolic syndrome criteria. These results
      demonstrate a strong association with insulin resistance. Men with several risk
      factors require specific care especially for hypertension and dyslipidemia that
      will be evaluated during the follow-up period. Genotyping of subjects having
      metabolic syndrome vs. controls for genes, presumably involved should enlarge the
      area of exploration of this syndrome.

PMID- 19160614
TI  - Ethics training for military medical trainees: the Brooke Army Medical Center
      experience.
AB  - Biomedical ethics training during graduate medical education programs is required
      by the Accreditation Council for Graduate Medical Education. Apart from this
      requirement, medical ethics education is an integral component of military
      medical practice. Although ethics education and training are required, tools to
      assess the effectiveness of ethics education are not well developed. Furthermore,
      although biomedical ethics education is mandated for new Army physician trainees,
      there has not been a systematic objective assessment of the effectiveness of that
      training. We report the concept underlying the design and implementation of a
      military biomedical ethics seminar for new Army physician trainees. Combining a
      didactic component and case analysis through small-group discussions, we
      emphasized providing tools to analyze ethical dilemmas both in the medical center
      environment and in the operational medicine environment. A total of 47 Army
      interns participated in the seminar. Eighty-nine percent of participants agreed
      or strongly agreed that the ethics orientation met expectations. Seventy-two
      percent agreed or strongly agreed that the information presented would affect
      their practice. Ninety-six percent thought that the small-group discussions were
      effective, and 80% thought that the presentations enhanced knowledge from medical
      school.

PMID- 19160615
TI  - Supporting the creation of new institutional review boards in developing
      countries: the U.S. Naval Medical Research Center Detachment experience.
AB  - The U.S. Naval Medical Research Center Detachment (NMRCD) has worked in Peru
      since 1983, conducting research on diseases of military importance in large part
      by interacting with multiple research partners across the scientific community of
      Central America and South America. Over the years, NMRCD has had research
      collaborations in Guatemala, Nicaragua, Costa Rica, Belize, Honduras, Suriname,
      Venezuela, Colombia, Ecuador, Bolivia, Chile, Uruguay, Paraguay, and Argentina.
      In addition to the various infectious diseases research collaborations, NMRCD has
      supported capacity building for research ethics and the creation of new
      institutional review boards. This article describes the contributions of NMRCD to
      research ethics training in Central America and South America, with specific
      emphasis on the support given to the creation of new institutional review boards.

PMID- 19160616
TI  - Military family physician attitudes toward treating obesity.
AB  - OBJECTIVE: The goal was to examine current knowledge, attitudes, and treatment
      practices of family practitioners regarding obesity. METHODS: A cross-sectional,
      anonymous, self-report survey of active members of the Uniformed Services Chapter
      of the American Academy of Family Physicians was performed. Measures included
      demographic information, attitudes toward obese patients, knowledge of associated
      health risks, and treatment recommendations, rated on a 5-point Likert scale.
      Results were compared with previous similar studies, and associations between
      demographic variables, physician body mass index, and attitudes and behaviors
      were examined by using multivariate regression analysis. RESULTS: Of the 1,186
      members invited to participate, 477 (40.2%) responded. Compared with previous
      studies, there was increased awareness of obesity-associated health risks and
      physicians' sense of obligation to counsel patients. There were minimal changes
      in physician comfort and gratification with obesity counseling. Stereotypical
      attitudes of physicians toward obese patients were increased. Treatment
      recommendations were increased in all fields, including exercise, diet/nutrition
      counseling, and behavioral modification, but the most notable increases were seen
      in the use of prescription medications, diet center programs, and surgical
      referrals. Age, physician gender, physician weight status, practice location, and
      current training status were each associated with some aspect of physician
      attitudes and treatment practices. CONCLUSION: Physicians are better able to
      identify obesity and its associated health risks, but some negative stereotypical
      attitudes persist. These attitudes affect current treatment practices. Increased
      awareness, training, and study are required to combat the continuing increase in
      obesity rates.

PMID- 19160617
TI  - Advance and retreat: tobacco control policy in the U.S. military.
AB  - This archival study explored why military tobacco control initiatives have thus
      far largely failed to meet their goals. We analyzed more than 5,000 previously
      undisclosed internal tobacco industry documents made public via an online
      database and additional documents obtained from the U.S. military. In four case
      studies, we illustrate how pressures exerted by multiple political actors
      resulted in weakening or rescinding military tobacco control policy initiatives.
      Our findings suggest that lowering military smoking rates will require health
      policymakers to better anticipate and counter political opponents. The findings
      also suggest that effective tobacco control policies may require strong, explicit
      implementation instructions and high-level Department of Defense support.
      Finally, policy designers should also consider ways to reduce or eliminate
      existing perverse incentives to increase tobacco consumption, such as allowing
      exchange store tobacco sales to fund Morale, Recreation, and Welfare Programs.

PMID- 19160619
TI  - The effects of an accelerated triage and treatment protocol on left without being
      seen rates and wait times of urgent patients at a military emergency department.
AB  - To combat increasing wait times and left without being seen (LWOBS) rates, our
      emergency department (ED) implemented an accelerated triage and treatment (TNT)
      protocol. A TNT team was allocated treatment rooms to begin management of urgent
      patients if a bed in the main ED was not available. A retrospective database
      study was performed using three separate 6-month periods: two control periods
      before the intervention (P1, P2) and one period after the intervention (P3). The
      primary outcome measures were LWOBS rate, time to evaluation, and total ED time
      for urgent patients. The time to be seen for EC3 patients improved from P1 to P3
      by an average of 12.6 minutes (18.5%, p < 0.0001) and from P2 to P3 by an average
      of 12.0 minutes (17.6%, p < 0.0001). The EC3 LWOBS rate decreased from 2.0% in P1
      and 1.9% in P2 to 0.8% in P3 (p < 0.0001 for both). The use of an accelerated TNT
      protocol was associated with a significant reduction in EC3 patient LWOBS rates
      and time to evaluation.

PMID- 19160618
TI  - Efficacy of the U.S. Army policy on hearing conservation programs.
AB  - Changes in U.S. Army hearing conservation policy require that many previous non
      noise hazardous areas be reclassified as noise hazardous and that employees in
      these areas be included in hearing conservation programs. The purpose of this
      study was to determine if a group of employees affected by this policy suffered
      occupational hearing loss between 1987 and 2001 while working in previously
      classified noise hazardous areas. The 45 subjects included in the study were
      demographically similar to the 211 from which they were selected. Differences
      between measured and predicted hearing thresholds in 1987 and in 2001 did not
      change significantly over the 15 years. Predicted noise-induced thresholds in
      2001 calculated from average noise exposures were not clinically significant. It
      was concluded that these subjects were adequately protected from hearing loss
      under the previous classification criteria and application of the new criteria
      provided no additional benefit.

PMID- 19160620
TI  - Pitfalls in aeromedical and ground crew engagement: lessons learned.
AB  - Aeromedical (AM) evacuation of trauma victims from action is an integral part of
      trauma care. The Israeli Air Force Rescue and Evacuation Unit is responsible for
      nearly all AM evacuations in Israel. We present three recent cases, within 1 year
      of operation, of engagement process failure during evacuations performed by the
      Rescue and Evacuation Unit. We then discuss possible pitfalls and lessons
      learned. In sum, we reveal that successful AM and ground crew engagement can save
      lives, as long as the engagement process is as short and efficient as possible.

PMID- 19160621
TI  - Orthopedic injuries in U.S. casualties treated on a hospital ship during
      Operation Iraqi Freedom.
AB  - From March to May 2003, the USNS Comfort was deployed to the Persian Gulf in
      support of combat operations for Operation Iraqi Freedom. The onboard orthopedic
      service treated 58 U.S. casualties during that period. Eighty-seven percent of
      the injuries were to the appendicular skeleton. Twenty-four percent were battle
      injuries, and 72% were nonbattle injuries. Patients with battle injuries tended
      to be younger and required more orthopedic operations than did patients with
      nonbattle injuries. Moreover, all patients with battle injuries were evacuated to
      higher echelons for further care, whereas 19% of patients with nonbattle injuries
      returned to duty in the short term. Complications were few, with no infections,
      amputations, or deaths. A descriptive review of the types of injuries, orthopedic
      care, and eventual disposition is presented.

PMID- 19160622
TI  - Army dental officer retention.
AB  - OBJECTIVE: The objective of this article was to identify major factors associated
      with the retention of Army dentists. METHODS: Customized survey instruments were
      designed. The 2006 survey was e-mailed to all Army Dental Corps captains and
      majors and the 2007 survey to all lieutenant colonels and colonels. Responses
      were returned by e-mail, fax, or traditional mail. RESULTS: Response rates were
      42% for the 2006 survey and 76% for the 2007 survey. More than one-half (53%) of
      junior officers responded as being highly unlikely or unlikely to remain on
      active duty, although the majority of senior officers reported being likely or
      very likely to remain in the Army until retirement. The results indicated that
      pay is a major driver for retention, because 72% of junior officers cited
      increases in bonuses as the first or second most important retention item. Sixty
      nine percent of junior officers thought that a bonus of $30,000 to $40,000 per
      year would be influential in retention. Pay was important to senior officers, but
      quality of practice, quality of life, and less frequent moves were rated higher
      than pay. All respondents felt that both senior and local leaders were aware of
      the retention issues but only 41% of junior officers, compared with 75% of senior
      officers, felt that action was being taken to address the issues. CONCLUSIONS:
      Retention of Army Dental Corps officers is multifactorial in nature. Pay is a
      major retention factor, but retention initiatives need to be broader in scope.

PMID- 19160623
TI  - Development and testing of a novel forward-deployable dental dressing.
AB  - The purpose of this study was to measure select properties of four temporary
      filling materials suitable for use in treating minor dental emergencies in the
      field. Specimens were made of each of the following four materials: intermediate
      restorative material, Fuji IX GP Fast, Ketac-Molar Quick, and the forward
      deployable dental dressing recently developed by the Naval Institute for Dental
      and Biomedical Research. Twenty-fours hours after specimen fabrication, five
      properties (hardness, compressive strength, diametral tensile strength, flexural
      strength, and flexural modulus) were measured for each of the materials and
      compared using analysis of variance and Tukey-Kramer tests to determine whether
      significant differences existed among the materials (alpha = 0.05). Data analysis
      revealed that significant differences existed among the products for all of the
      properties tested. The forward-deployable dental dressing's properties compared
      favorable with and, in many cases exceeded those of intermediate restorative
      material, Fuji IX GP Fast, and Ketac-Molar Aplicap Quick.

PMID- 19160624
TI  - Comparison of flexural strength between fiber-reinforced polymer and high-impact
      strength resin.
AB  - Fractures of polymer material are one of the most frequent reasons for the repair
      of removable dental prostheses. Therefore, there is a constant endeavor to
      strengthen them, and polymer materials with high resistance to fracture are being
      developed. The aim of this study was to determine the flexural strength of
      polymer materials and their reinforcements and thus give preference to their
      clinical use. Specimens with dimensions 18 x 10 x 3 mm were tested after
      polymerization, immersion in water at a temperature 37 degrees C for 28 days, and
      thermocycling by using the "short-beam" method to determine the flexural
      strength. Microscopic examination was performed to determine the quality of
      bonding between the glass fibers and matrix. Common polymer materials (control
      group) demonstrated the lowest flexural strength, although, when reinforced with
      fibers they showed higher flexural strength, matching that of the tested high
      impact strength resin. Thermocycled specimens had the highest flexural strength,
      whereas there was no difference (p > 0.05) between specimens tested after
      polymerization and immersion in water.

PMID- 19160625
TI  - Estimated mental health and analysis of relative factors for new Chinese
      recruits.
AB  - OBJECTIVE: The primary aim of the present study was to quantitatively assess and
      analyze influential psychosocial factors in the mental health of new military
      recruits. METHODS: A total of 2,734 army recruits were evaluated by using the
      Symptom Checklist-90 (SCL-90) and Trait Meta-Mood Scale. RESULTS: In general, the
      army recruits were found to be in a good state of mental health. The SCL-90
      scores of the new recruits were significantly higher than those of the normal
      civilian population (p < 0.01). The new recruits were similar to the normal army
      population, with notable exceptions in the following three scales: obsessive
      compulsive, depression, and anxiety (p < 0.01 or p < 0.05). Factors that
      significantly influenced the SCL-90 scores included childhood environment,
      education level, and parental relationship. Results from the current study also
      revealed negative associations between the SCL-90 global severity index and the
      Trait Meta-Mood Scale subscale scores (p < 0.01). CONCLUSION: The mental health
      status of army recruits is closely related to their childhood environment,
      education level, parental relationship, and emotional intelligence. These factors
      should be considered by mental health workers, to help new army recruits adapt to
      the new environment.

PMID- 19160626
TI  - Adaptation and quality of life among long-term cervical cancer survivors in the
      military health care system.
AB  - OBJECTIVE: This study assessed quality of life in long-term cervical cancer
      survivors eligible for health care in the military health system. METHODS:
      TRICARE beneficiaries who were diagnosed as having cervical cancer in 1980 to
      2000 completed self-administered questionnaires including standardized measures
      of quality of life, distress, and sexuality. RESULTS: Forty-one women (72% of
      those who received questionnaire packets) provided questionnaire data. More than
      2,500 questionnaires were undeliverable, with no forwarding address. Data
      indicated that quality of life, cervical cancer-related stress, and intimacy
      concerns were comparable to population normative values. Survivors received more
      cancer screenings than the general population. Nearly one-half of respondents
      reported no effect of cancer on their sexual relationships, whereas approximately
      one-half said that cancer had a negative impact. CONCLUSIONS: Although cervical
      cancer survivors overall reported a high quality of life, many experienced
      significant decrements in sexual functioning. The Automated Central Tumor
      Registry presents challenges and potential for conducting this kind of research.

PMID- 19160627
TI  - Rhabdomyolysis associated with bupropion use as a smoking cessation adjunct:
      review of the literature.
AB  - A case of rhabdomyolysis associated with a therapeutic dose of bupropion
      sustained release is presented. Other features of the use of bupropion are also
      discussed.

PMID- 19160628
TI  - A 31-year-old Army specialist presenting with acute oligoarthritis.
AB  - A 31-year-old Army specialist was evaluated at Walter Reed Army Medical Center
      for an acute attack of arthritis in the left hand. After an initial evaluation,
      the patient was referred to the rheumatology service, and gout was diagnosed on
      the basis of synovial fluid analysis. This case demonstrates an uncommon
      presentation of a common disorder in an active duty soldier. The discussions
      presented following the clinical data are meant to expand diagnostic
      considerations for patients with similar symptoms, to address risk factors for
      gout relevant to the military, and to clarify the management of gout.

PMID- 19160629
TI  - Two successful vaginal births after cesarean section in a patient with Hermansky
      Pudlak syndrome who was treated with 1-deamino-8-arginine-vasopression during
      labor.
AB  - We describe the obstetric management for a patient with Hermansky-Pudlak syndrome
      (HPS) and a previous cesarean delivery. The disease is characterized by
      oculocutaneous albinism, platelet storage dysfunction, and lipofuscin deposits in
      the reticuloendothelial system. Patients with the disorder are at high risk for
      major morbidity secondary to bleeding complications. The patient was a 22-year
      old military spouse from Puerto Rico with HPS and a history of severe hemorrhage
      during cesarean delivery of her first child. In this report, we discuss the
      pathophysiologic features of HPS and the prophylactic administration of 1-deamino
      8-arginine-vasopression during labor to minimize blood loss.

PMID- 19160630
TI  - Radiology corner. Answer to last month's radiology case (28): Pneumocystis
      jiroveci pneumonia.

PMID- 19160631
TI  - Technology will have major impact on shaping future EDs, say the experts.
AB  - Technology can be a tremendous aid to any ED, if it is used properly, and it will
      have a growing role over the next 20 years. You might wish to enlist the help of
      pre-nursing or pre-law students to serve as "scribes," so that your doctors and
      nurses can spend less time at the computer and more time with patients. Be
      prepared for an increasingly informed patient population, many of whom may have
      gone online and have already "diagnosed" themselves. Stay on top of new
      technology that might improve care and safety, such as the "life stretcher," a
      mattress cover that automatically reads patients' vitals.

PMID- 19160632
TI  - EDs must learn from past to solve nagging problems.
AB  - ED experts say that we can learn from the key developments of the past 20 years
      to help improve the way EDs operate in the future. Here are a few suggestions for
      adapting to the challenges that have arisen: Develop physician leadership of the
      triage process to reduce lengthy delays on the front end of the care process.
      Support modification in liability legislation to lighten the burden placed on EDs
      by the Emergency Medical Treatment and Labor Act (EMTALA). Design new EDs or
      expansions to accommodate the needs of elderly patients, who will comprise a much
      larger segment of the patient population.

PMID- 19160633
TI  - Economy predicted to put more pressure on EDs.
AB  - There is nothing that you, as an ED manager, can do to improve the nation's
      economy, but knowing what to expect will enable you to make more informed
      decisions about department operations. Here is what the experts say you should
      expect: Your patient census is likely to increase as more people become
      unemployed and lose their health insurance. It will be more important than ever
      to improve documentation where possible, assure correct coding and billing,
      perform internal audits and self-disclose overpayments before Medicare/Medicaid
      identify them. As hospital revenues drop, expect to see a 'substantial' impact on
      your ability to compensate ED physicians. (For more on ED manager salaries, see
      the ED Management 2008 Salary Survey results enclosed in this issue.).

PMID- 19160634
TI  - Standards endorsed to boost efficiency, quality.
AB  - While the new ED standards endorsed by the National Quality Forum are voluntary,
      many, if not all, of them eventually could be adopted by the Centers for Medicare
      & Medicaid Services (CMS). They already are eligible for public reporting. They
      also indicate ways in which ED quality of care can be improved. Review the
      measures and begin to plan for their measurement and utilization in their own
      departments, in anticipation of CMS adoption. Pay particular attention to some
      new clinical measures that help monitor quality: bundling, documenting wait time,
      and weight in kilograms for children. The measures will enable you to get a sense
      of your department's baseline, particularly with throughput.

PMID- 19160635
TI  - [Ethics in Orthopedics].

PMID- 19160636
TI  - [Doctor, is my fracture solid?].
AB  - The adequate treatment of fractures consists of a conservative or surgical
      approach whose goal is to assure a rapid solidity of the fracture site that will
      lead to a durable complete healing without complications. Fracture healing
      criteria remain controversial. In this article we are trying to present the tools
      used in the evaluation of bone consolidation and propose therapeutical guidelines
      aiming at the return to daily activities in full security.

PMID- 19160637
TI  - [Pelvic trauma].
AB  - Pelvic trauma A great variety of very polymorphous lesions of pelvic trauma are
      deffering from each other by their context, their anatomical aspect and
      therapeutic implication. In the isolated acetabular fractures, function is mainly
      at stake. The management consists mainly of re-establishing a joint congruence to
      prevent early coxarthrosis. Pelvic fractures often occur in violent trauma and
      are associated with visceral lesions, putting vital prognosis at stake. In case
      of hemodynamic shock, external fracture stabilization when it is indicated
      associated to embolisation of pelvic bleeding if necessary and after external
      fixation are preponderant.

PMID- 19160638
TI  - [Surgery of the rheumatoid foot and ankle].
AB  - Surgery of the rheumatoid foot and ankle Initial presentation of rheumatoid
      arthritis (RA) will be foot and ankle symptoms in 20% of cases. Eventually, 50
      90% of patients will develop foot and ankle alterations. Typical deformities of
      the forefoot include hallux valgus and dorso-lateral dislocation of the lesser
      metatarso-phalangeal joints. RA involvement of the hindfoot frequently leads to
      plano-valgus deformity. Approximately 20% of surgery performed for RA is done at
      the foot and ankle. Early surgery is efficient against pain and deformity.
      Patient's satisfaction rate after surgery is high despite a slight higher
      complication rate compared to conventional foot and ankle surgery.

PMID- 19160639
TI  - [Total knee arthroplasty today: what should we tell our patients?].
AB  - Total knee arthroplasty (TKA) remains the preferred treatment for patients with
      invalidating osteoarthritis. It allows these patients to find once again a
      satisfactory quality of life. These results are reflected by the increasing
      number of interventions performed each year and in always younger patients. The
      objective of this review of the scientific literature was to determine the long
      term quantitatively and qualitatively results of TKA and determine the parameters
      which could influence the long-term outcome. There does not seem to be any clear
      arguments in favor of one type of implant or surgical technique. One also notices
      that TKA in females and older patients seem to have longer lifespan, estimated to
      approximately 15 years. The most frequent complication remains aseptic loosening
      followed by infections.

PMID- 19160640
TI  - [Anterior cruciate ligament reconstruction: indications and techniques].
AB  - The anterior cruciate ligament (ACL) is a key structure for the knee joint
      stability and is frequently injured. Patients can be classified as "low-risk" or
      "high-risk" to have subsequent knee instability or meniscal injuries. This risk
      is based on the pre-injury level of sports participation and on the initial knee
      stability. For low-risk patients (mostly sedentary, senior), conservative
      treatment with physiotherapy leads to a satisfactory outcome. For high-risk
      patients (the young, competitive athlete), early ligament reconstruction is
      mandatory. Numerous ACL reconstruction techniques exist with auto- or allografts.
      However these guidelines must be adapted to the patient characteristics,
      motivations and expectations, in order to offer a treatment "a la carte".

PMID- 19160641
TI  - [Musculoskeletal tumours misdiagnosed as sport injuries].
AB  - During our medical activity, we would necessarily be confronted with sport
      related complaints. Most of the diagnosed pathologies belong to the inflammation
      category and other traumas. However, as we will see in this review, we sometimes
      discover musculoskeletal tumours from different origins. One should never
      underestimate non-developing or slowly developing conditions among athletes, and
      to keep in mind a possible oncologic diagnosis. A critical assistance for
      diagnosis is given by the medical imagery with MRI being the leading technique.
      The aim is to avoid any delay in making the correct diagnosis, and therefore to
      avoid a more severe prognosis that would lead to a more radical surgery for
      either benign or malign tumours.

PMID- 19160642
TI  - [10 years of lipodystrophy--and so many uncertainties].
AB  - HIV lipodystrophy is characterized by peripheral, subcutaneous lipoatrophy in the
      face, arms, legs, and buttocks and central fat accumulation in the neck, breasts,
      and abdomen (referred as lipohypertrophy). Lipodystrophy is associated with
      atherogenic lipid abnormalities, low levels of HDL cholesterol, insulin
      resistance, and, less commonly, hyperglycaemia. Causes of lipodystrophy are not
      completely elucidated. The prevalence of lipodystrophy ranges from 20% to 70% of
      the patients after one year of ART, depending on the type of ART, with lower
      prevalence in more recent studies of newer agents. Treatment strategies are
      disappointing. A multidisciplinary approach is now proposed in the Geneva
      University Hospital in order to coordinate efforts from different department,
      including internal medicine, infectiology or esthetic surgery for example.

PMID- 19160643
TI  - [A new miracle treatment in the fight against addictions? Prudence in light of
      the promises of Prometa].

PMID- 19160644
TI  - [Malaria: the vaccine enters a phase III trial].

PMID- 19160645
TI  - [Sacred DNA (I)].

PMID- 19160646
TI  - [Gulf War Syndrome exists].

PMID- 19160647
TI  - [Is health a right?].

PMID- 19160648
TI  - Cervical length screening in patients who have undergone loop electrosurgical
      excision procedure.
AB  - OBJECTIVE: To determine whether cervical length measurements in patients who have
      undergone a loop electrosurgical excision procedure (LEEP) is a predictor of
      spontaneous preterm delivery (PTD) at < 35 weeks. STUDY DESIGN: A retrospective
      chart review of 97 pregnant patients with a history of prior LEEP undergoing
      cervical length screening by transvaginal ultrasound (TVUS) was done. Of these,
      87 were included in the study. All patients delivered at the St. Luke's Hospital
      and Health Network over a 5-year study period. Cervical length measurements in
      the LEEP group were included. Incidence of PTD in patients who have undergone
      prior LEEP was compared to patients delivered during the same period who had not
      undergone LEEP. RESULTS: Of 87 patients who had undergone LEEP, 3 (3.4%, 95% CI
      1.1-9.6%) delivered at < 35 weeks. None of the 3 patients had cervical shortening
      on TVUS. The PTD rate was not statistically different in the LEEP and non-LEEP
      groups. A shortened cervix was noted in 4 of the 87 patients in the LEEP group
      (4.5%, 95% CI 1.8-11%) but none had a PTD. CONCLUSION: Cervical length screening
      in LEEP patients may not be a predictor of PTD.

PMID- 19160649
TI  - Analysis of disease in the obstetric intensive care unit at a university referral
      center: a 24-month review of prospective data.
AB  - OBJECTIVE: To determine the current spectrum of disease in an obstetric
      population resulting in admission to the intensive care unit (ICU) at a tertiary
      care hospital. STUDY DESIGN: Analysis of data from obstetric patients admitted
      for critical care management at the University of Maryland Medical Center over a
      24-month period. RESULTS: Critical care admission was required for 34 (1.3%) of
      2,565 women admitted for deliveries; 38.5% of patients were delivered during
      their ICU admission. Preexisting medical conditions were present in 67.6% (76.5%
      were in the antenatal period vs. 23.5% in the postpartum period). Conditions
      leading to ICU admission included organ system failure, respiratory failure,
      central nervous system disease, cardiac failure, preeclampsia and postpartum
      hemorrhage. The median Acute Physiology and Chronic Health Evaluation II (APACHE
      II) score overall was 11.0 (antenatal 12.0, postpartum 10.5). Although the
      predicted maternal mortality rate was 12.9% (14.6% in the antenatal period and
      12.1% in the postpartum period), the actual mortality rate was 0%. CONCLUSION: In
      this population, the antenatal period now accounts for the majority of ICU
      admissions. Respiratory failure (mainly from infectious etiologies) has surpassed
      obstetric hemorrhage as the primary reason for ICU admission. Finally, the APACHE
      II scoring system is inaccurate for use in an obstetric population.

PMID- 19160650
TI  - A survey on diagnosis and treatment of vulvodynia among vulvodynia researchers
      and members of the International Society for the Study of Vulvovaginal Disease.
AB  - OBJECTIVE: To survey members of the International Society for the Study of
      Vulvovaginal Disease and authors of recent related medical publications for whom
      e-mail addresses were available to assess current opinion and practices. STUDY
      DESIGN: In a cross-sectional online survey of potential participants,
      characteristics of respondents and their preferred diagnostic criteria and
      treatment modalities for vulvodynia were assessed using univariate and
      multivariate methods. RESULTS: Of recipients, 61.0% completed the survey. Of
      these, 86.7% were active in diagnosing or treating women with vulvodynia and
      41.3% were currently active in vulvodynia research. Of respondents, > 80% include
      a history, a genital visual examination and vulvar pressure sensitivity testing
      in their evaluation of women with vulvar pain. Laboratory assessments were less
      likely to be rated essential or helpful. Of participants, > 80% rated as very
      effective or somewhat effective tricyclic antidepressants, pelvic floor physical
      therapy and psychologic counseling. Most indicated they have made the diagnosis
      of vulvodynia in conjunction with other vulvovaginal diagnoses and agreed that
      vulvodynia does remit for some women. CONCLUSION: Despite many diagnostic and
      treatment options available, some consensus on diagnostic and treatment
      preferences for vulvodynia was identified. Further research to develop the
      evidence base for diagnostic and treatment decisions is needed.

PMID- 19160651
TI  - Clinical value of tumor markers in gestational trophoblastic diseases.
AB  - OBJECTIVE: To determine the clinical importance of serum biomarkers in diagnosis
      of gestational trophoblastic disease (GTD). STUDY DESIGN: Sixty-nine pregnant
      women with molar pregnancy and 19 healthy pregnant women with corresponding age,
      gravity, parity and gestational age were matched. Serum levels of human chorionic
      gonadotropin (hCG), alpha-fetoprotein (AFP), CA 125, CA 19-9, CA 15-3, CA 242 and
      carcinoembryonic antigen (CEA) were measured using enzyme-linked immunosorbent
      assay (ELISA). Mean serum values were compared between the groups using Mann
      Whitney, chi2 and paired t tests. RESULTS: AFP levels were higher in the control
      group. CA 19-9 serum values are increased in patients with GTD. Comparing mean CA
      19-9 serum levels between the groups demonstrated a meaningful relation (p =
      0.012). CA 125, CA 15-3, CA 242 and CEA are not affected by molar pregnancy, and
      no significant difference was observed between the groups. CONCLUSION: Low AFP
      levels and increased CA 19-9 levels can be used as tumor markers in diagnosis of
      molar pregnancies in conjunction with clinical and sonographic findings and serum
      levels of hCG. Serum levels of CA 125, CA 15-3, CA 242 and CEA did not provide
      reliable information in diagnosis of GTD.

PMID- 19160652
TI  - Profile of outpatient hysteroscopy in the United States from 1994 to 1996.
AB  - OBJECTIVE: To estimate use of hysteroscopic surgery for evaluating genital tract
      bleeding and related disorders. STUDY DESIGN: Using the U.S. National Survey of
      Ambulatory Surgery, we performed a retrospective, cross-sectional study of women
      undergoing outpatient hysteroscopy. Rates of procedures were tabulated for all
      years available (1994-1996). Comparison was made across age, ethnicity, and
      geographic distribution. Complication rates for operative injury and pulmonary
      edema were estimated from corresponding diagnosis codes. RESULTS: The estimated
      number of women undergoing outpatient hysteroscopy was 197,800, 225,900 and
      232,000 for the years 1994-1996, respectively. Twenty percent of cases included
      operative hysteroscopy. Commonly associated diagnoses included menorrhagia,
      postmenopausal bleeding, uterine polyps and leiomyoma. The most common
      concomitant procedures performed included dilation and curettage, laparoscopy and
      uterine lesion destruction, not elsewhere classified. Complication rates were 2.3
      per 1,000 hysteroscopies, but 3 times higher for operative hysteroscopy.
      CONCLUSION: Hysteroscopy is a commonly performed procedure in the United States,
      largely in association with uterine bleeding disorders.

PMID- 19160653
TI  - Outcomes for abdominal myomectomies among high-volume surgeons.
AB  - OBJECTIVE: To examine the relationship between surgical volume and complications
      and resource utilization for myomectomy. STUDY DESIGN: This retrospective cross
      sectional study in a university hospital setting (Brigham and Women's Hospital)
      analyzed 527 consecutive women with uterine fibroids who underwent abdominal
      myomectomy. A multivariate analysis was performed to determine the association
      between surgical volume and outcomes. RESULTS: There were no significant medical
      or surgical complications following myomectomy. However, high-volume surgeons did
      procedures significantly faster, they collected more tissue per time and their
      patients had less blood loss. CONCLUSION: The surgical volume of the physician
      does not affect the safety of abdominal myomectomy. However, high-volume surgeons
      had more efficient resource utilization than did physicians doing fewer cases.

PMID- 19160654
TI  - Outcome of treated anogenital intraepithelial neoplasia among human
      immunodeficiency virus-infected women.
AB  - OBJECTIVE: To determine characteristics and clinical course of high-grade
      anogenital intraepithelial neoplasia (AIN) in human immunodeficiency virus (HIV)
      infected women. STUDY DESIGN: HIV-positive women with biopsy-proven high-grade
      (II and III) vulvar (VIN), vaginal (VAIN) or perianal intraepithelial neoplasia
      (PAIN) were identified in the electronic databases of 2 colposcopy clinics.
      RESULTS: A total of 31 patients were identified from 1992 to 2007, of which 30
      had a mean follow-up of 47.7 months (SD = 46.0; range, 2.6-166.2). Of the
      patients, 77.4% had VIN, 12.9% VAIN and 9.7% PAIN at first diagnosis. Age at
      diagnosis of IN was 36.2 years (SD +/- 5.2; range, 23.5-47.0). Ninety percent of
      patients received antiretroviral therapy at first diagnosis of IN; 65% (13 of 20)
      of patients with a follow-up of > 2 years required a second treatment, and 2
      developed invasive vulvar cancer (10%). CONCLUSION: AIN among HIV-positive women
      shows a high relapse rate despite treatment modality used and a substantial
      invasive potential.

PMID- 19160655
TI  - Women's perception of the outcome of the surgical management of vulvar
      intraepithelial neoplasia.
AB  - OBJECTIVE: To assess women's perception of the effects of vulvar surgery for
      vulvar intraepithelial neoplasia (VIN). STUDY DESIGN: Women attending a vulvar
      clinic for routine follow-up after surgical treatment of VIN were invited to
      respond to a brief questionnaire relating to their perception of vulvar
      appearance and sexual function. Clinical details, including the patients' age,
      parity, the focality and size of the lesion, types of treatment and length of
      follow-up, were extracted from the medical records. The diagnosis of VIN was made
      according to the histologic criteria of the International Society for the Study
      of Vulvovaginal Disease. RESULTS: Only 2 of 70 (3%) women expressed
      dissatisfaction following surgical treatment. One woman described vulvar
      disfigurement and the second had diminished sexual satisfaction following
      surgery. CONCLUSION: There is a high level of patient satisfaction following
      conservative surgery for VIN.

PMID- 19160656
TI  - Obstetric practice in the United States of America may contribute to the obesity
      epidemic.
AB  - The recommended weight gain of pregnancy in women over the past years has
      increased from 17.6 lb in 1945 to 25-35 lb in 1990. This has been associated with
      larger infant birth weights, more difficult deliveries and increased obesity in
      children and adults, with little benefit in reducing perinatal morbidity. It may
      be time to reevaluate the amount of weight normal pregnant women should gain.

PMID- 19160657
TI  - Lipid systems and techniques. Introduction.

PMID- 19160658
TI  - Eicosanoids: generation and detection in mammalian cells.
AB  - Eicosanoids are 20-carbon lipids generated by the oxidation of arachidonic acid
      that are involved in physiological signaling in virtually all organ systems.
      Three primary enzymatic pathways are responsible for their synthesis in mammalian
      cells: lipoxygenase, cyclooxygenase, and cytochrome P450. They signal through
      receptor-dependent pathways, and their dysregulation is central to numerous
      pathological states including cancer and inflammation. Recent advances in their
      detection and analysis using mass spectrometry have made the study of these
      molecules more accessible to the research community in general. This review
      focuses on the available methods for the detection and analysis of eicosanoids
      and aims to act as a guide for those wishing to approach the analysis of
      eicosanoids for their own research.

PMID- 19160659
TI  - Lipidomic analysis of phospholipids and related structures by liquid
      chromatography-mass spectrometry.
AB  - Lipids are highly dynamic molecules with many different roles ranging from
      structural to signaling. Alterations in particular lipid levels change cellular
      behavior. In humans, inappropriate changes may manifest as diseases such as
      Alzheimer's, atherosclerosis, diabetes, obesity, and even cancer. This has led to
      a great interest in monitoring lipid changes both during normal cellular
      processes and in disease situations. With the advent of rapid mass spectrometry,
      it has become possible to analyze many lipids within a single sample with
      unsurpassed sensitivity and detail. Coupling this with liquid chromatography
      potentially enables the complete profiling of all the phospholipids, both major
      and minor, from a single sample within a single analysis run.

PMID- 19160660
TI  - Measurement of polyphosphoinositides in cultured mammalian cells.
AB  - The seven phosphorylated derivatives of phosphatidylinositol (PtdIns), often
      collectively referred to as polyphosphoinositides (PPIn), are a minor component
      of eukaryotic cell membranes. Nevertheless, their synthesis is needed for an ever
      increasing spectrum of cellular processes, including regulation of the actin
      cytoskeleton, chemotaxis, membrane trafficking, glucose uptake, and organelle
      acidification. PPIn metabolism is regulated dynamically by a network of kinases
      and phosphatases. Furthermore, synthesis of PPIn can be provoked by external
      stimuli; for example, the second messenger phosphatidylinositol 3,4,5
      trisphosphate rapidly and transiently accumulates in cells challenged with
      agonists such as PDGF that activate receptor tyrosine kinases. The measurement of
      PPIn levels in in vivo cultured cells has been vital to our understanding of the
      metabolism and function of these important signaling molecules; methods are
      described herein that allow measurement of PPIn levels in culture cells in vivo.

PMID- 19160661
TI  - Inositol lipid-dependent functions in Saccharomyces cerevisiae: analysis of
      phosphatidylinositol phosphates.
AB  - Inositol phospholipids regulate many cellular processes, including cell survival,
      membrane trafficking, and actin polymerization. Quantification of inositol lipids
      is one of the essential techniques needed for studies that aim to decipher
      inositol lipid-dependent cellular functions. The study of phosphoinositides in
      most organisms is hampered by a lack of facile genetic tools. However, the
      essential elements of most inositol lipid signaling pathways appear to be
      conserved across eukaryote phylogeny. They can therefore readily be elucidated
      (both genetically and biochemically) in the budding yeast Saccharomyces
      cerevisiae. Because of the low abundance of polyphosphoinositides in cells, many
      analytical methods start by radioactively labeling intact cells and then
      extracting the lipids with chloroform/methanol/ water mixtures based on those
      first devised half a century ago. Yeast present special extraction problems
      because the cell wall must be broken in order to facilitate solvent access and
      maximize lipid yield. Once lipids have been extracted, fatty acids are removed
      and the resulting water-soluble glycerophosphoinositol phosphates are analysed by
      anion-exchange HPLC. This chapter describes how to extract and quantify the
      inositol lipids of S. cerevisiae cells that have been radiolabeled to isotopic
      equilibrium with [3H]myo-inositol.

PMID- 19160662
TI  - Methods for the determination of the mass of nuclear PtdIns4P, PtdIns5P, and
      PtdIns(4,5)P2.
AB  - Phosphatidylinositol (PtdIns) and its phosphorylated derivatives represent less
      than 5% of total membrane phospholipids in cells. Despite their low abundance,
      they form a dynamic signaling system that is regulated in response to a variety
      of extra- and intracellular cues. Protein domains including PH, FYVE, ENTH, PHOX,
      PHD fingers, and lysine-/arginine-rich patches can bind to specific
      phosphoinositide isomers, which, in turn, can induce changes in the subcellular
      localization, posttranslational modification, protein interaction partners, or
      activity of the protein containing such a domain. Phosphoinositides and the
      enzymes that synthesize them are found in many different subcellular compartments
      including the nuclear matrix, heterochromatin, and sites of active RNA splicing,
      suggesting that phosphoinositides may regulate specific functions within the
      nuclear compartment. The existence of distinct subcellular pools has led to the
      challenging task of the quantitation of temporal and spatial changes in
      phosphoinositides. We report methods to measure the mass levels of three
      different phosphoinositides within the nuclear compartment.

PMID- 19160663
TI  - Lipid quantification and structure determination of nuclear envelope precursor
      membranes in the sea urchin.
AB  - Nuclear envelope assembly is a fundamental cellular process normally taking place
      once in every cell cycle in eukaryotes. The timing of fusion of nuclear membrane
      precursors to form the complete double membrane surrounding the chromosomes is
      tightly controlled, but much remains unclear concerning its regulation. Small
      amounts of material available and the high background of irrelevant cellular
      membranes have limited detailed analysis. We have employed several sensitive and
      high-resolution techniques to analyze the nuclear membrane structure,
      composition, and dynamics using purified membrane fractions and a cell-free
      system that results in nuclear envelope formation. We discuss the application of
      cholesterol and phospholipid colorimetric assays, fluorescent filipin labeling,
      electrospray ionization tandem mass spectrometry coupled to HPLC (HPLC
      ESI/MS/MS), electron microscopy (EM), and solid-state nuclear magnetic resonance
      (NMR) spectroscopy. Colorimetric assays determine the amounts of inorganic
      phosphates from phospholipids and cholesterol/ cholesteryl esters present in
      membrane-containing fractions. Filipin staining of natural membranes allows the
      localization and relative quantification of cholesterol. HPLC-ESI/MS/MS
      determines the quantitative composition of membrane phospholipid species from
      small amounts of membranes. Cryosectioning of cryoprotected sperm cells
      facilitates EM verification of membrane domains existing in vivo. Deuterium solid
      state NMR provides information about membrane rigidity and lipid-phase behavior.
      The sensitivity, quantification, and structural determinations provided by these
      techniques should prove useful in studying membrane dynamics in a variety of
      systems exhibiting membrane fusion.

PMID- 19160664
TI  - Solution and solid-state NMR of lipids.
AB  - Lipid structure and dynamics are of first importance for cellular function.
      Lipids such as phosphatidyl inositol (PtdIns) are essential in signaling
      pathways, as they are recognition sites at the membrane surface. Their headgroup
      or chain structure appears to be crucial for such a signaling role. Other lipids
      such as cholesterol and sphingomyelin are key molecules in maintaining membrane
      integrity and are the building blocks of membrane domains, such as "rafts." It is
      essential to have techniques that can decipher both the structure and dynamics of
      various classes of lipids. With its liquid-state and solid-state facets, NMR is a
      very powerful tool for such a determination. We show that lipids extracted from
      membranes and dissolved in organic solvents can reveal their molecular structure
      when observed with multinuclear one-dimensional or two-dimensional NMR. We also
      show that multinuclear solid-state NMR provides information on the nature of the
      membrane phase (lamellar, hexagonal, isotropic, etc.), its dynamics (fluid or
      gel, or liquid ordered with cholesterol), and the molecular structure of embedded
      lipids when using the magic angle spinning apparatus. Typical examples of
      relatively simple experiments are shown both with liquid- and solid-state NMR of
      lipids.

PMID- 19160665
TI  - Spatial localization of PtdInsP2 in phase-separated giant unilamellar vesicles
      with a fluorescent PLC-delta 1 PH domain.
AB  - This chapter describes a method for the preparation of giant unilamellar vesicles
      containing phosphatidylinositol 4,5-bisphosphate that are larger than 20 microm
      in size. The phospholipids composition of the vesicular membrane is such that
      fluid lamellar and liquid-ordered or gel phases are formed and separate within
      the confines of one vesicle. It outlines the preparation of a protein fluorescent
      label, pleckstrin homology domain from phospholipase C-delta 1, that binds
      specifically to phosphatidylinositol 4,5-bisphosphate. Using fluorescence
      microscopy, the presence and spatial position of this phosphorylated
      phosphatidylinositol lipid on the lipid membrane have been located with the
      pleckstrin homology domain. We show that phosphatidylinositol 4,5-bisphosphate
      and the phospholipase C-delta 1 pleckstrin homology domain are located to the
      fluid phase of the vesicle membrane. This approach can therefore show how
      membrane physical properties can affect enzyme binding to phosphatidylinositol
      4,5-bisphosphate and thus further the understanding of important membrane
      processes such as endocytosis.

PMID- 19160666
TI  - Studying cell-to-cell interactions: an easy method of tethering ligands on
      artificial membranes.
AB  - Extensive studies have been performed in order to understand the interaction of
      receptors with soluble ligands. However, we know very little of the parameters
      that regulate the interaction of receptors with membrane-bound ligands.
      Artificial lipid bilayers can be used to mimic cell-to-cell interactions, but a
      major challenge remains how to tether molecules to these membranes. We describe a
      simple and reliable method to tether ligands on glass-supported artificial
      bilayers containing biotinylated lipids. In this system, the model antigen hen
      egg lysozyme (HEL) is tethered through a fluorescently labeled streptavidin
      monobiotinylated anti-HEL antibody bridge. This allows us to study the
      interaction of HEL-specific B cells with the tethered antigen by a variety of
      microscopy techniques. We recently used this system to study the activation of B
      cells by membrane antigens.

PMID- 19160667
TI  - Ceramide-induced transbilayer (flip-flop) lipid movement in membranes.
AB  - Lipids in biological membranes are asymmetrically distributed across the bilayer.
      The choline-containing lipids, phosphatidylcholine (PtdCho) and sphingomyelin
      (SM), are more abundant in the external leaflet. In contrast, the amino
      containing glycerophospholipids, phosphatidylserine (PtdSer) and
      phosphatidylethanolamine (PtdEth), are located preferentially on the cytoplasmic
      leaflet. The maintenance of transbilayer lipid asymmetry is essential for normal
      membrane function, and disruption of this asymmetry is associated with cell
      activation or pathological condition. The physiological role of ceramide
      formation in response to cell stimulation remains controversial. Ceramide
      formation serves many different functions at various locations in the cell.
      Despite the limited capacity for spontaneous intracellular diffusion or membrane
      flip-flop of lipids in membranes, we have found that ceramide production, via
      sphingomyelinase action or addition of external ceramide, induces the
      transbilayer lipid motion of the lipids within the cellular membrane. This
      chapter outlines various commonly used assays for measuring lipid flip-flop
      induced by ceramide in cell and model membranes.

PMID- 19160668
TI  - Effects of sterols on the development and aging of Caenorhabditis elegans.
AB  - Although Caenorhabditis elegans lacks several components of the de novo sterol
      biosynthetic pathway, it requires sterols as essential nutrients. Supplemental
      cholesterol undergoes extensive enzymatic modification in C. elegans to form
      certain sterols of unknown function. Since sterol metabolism in C. elegans
      differs from that in other species, such as mammals and yeast, it is important to
      examine how sterols regulate worm physiology. To examine the functions of sterols
      in C. elegans, a sterol-feeding experiment was carried out and several critical
      parameters, such as brood size, growth rate, and life span, were measured. In
      addition, the change in lipid distribution in C. elegans can be both
      qualitatively and quantitatively determined by various methods, including
      staining and chromatographic techniques. Taken together, the effects of sterols
      on C. elegans are very prominent and can be easily assessed using the techniques
      described here.

PMID- 19160670
TI  - Lipid metabolism and recognition. Introduction.

PMID- 19160669
TI  - Proteomic analysis of the sterol-mediated signaling pathway in Caenorhabditis
      elegans.
AB  - Since Caenorhabditis elegans is incapable of de novo cholesterol biosynthesis, it
      must utilize other nonpermissive sterols that are present in the environment by
      converting them into cholesterol for cellular function. The inhibition of sterol
      conversion to cholesterol in C. elegans by various sterol biosynthesis inhibitors
      (SBIs) is known to cause serious defects in the development of these worms. To
      determine the biochemical consequences of these physiological abnormalities, one
      can perform a proteomic analysis of worms of a certain stage that are grown in
      the presence of SBIs in order for the differential expression of proteins
      involved in the sterol-mediated signaling pathway to be identified. For example,
      reductions in the expression of lipoprotein family members, such as vitellogenin
      2 and vitellogenin-6, are prominent in azacoprostane-treated worms. This
      phenomenon is also seen in worms treated with AY-9944, which blocks the
      conversion of 7-dehydrocholesterol, a major sterol present in C. elegans, to
      cholesterol.

PMID- 19160671
TI  - Studying the subcellular localization and DNA-binding activity of FoxO
      transcription factors, downstream effectors of PI3K/Akt.
AB  - This chapter describes methods for studying downstream events of the PI3K/Akt
      signaling cascade, focusing on the FoxO transcription factors. These approaches
      also represent alternative means for gauging the phosphoinositide-3 kinase/Akt
      activity. We describe protocols for the fractionation of cytoplasmic and nuclear
      protein extracts and for studying transcription factor DNA-binding activity in
      vitro and in vivo.

PMID- 19160672
TI  - Measurement of PTEN activity in vivo by imaging phosphorylated Akt.
AB  - This chapter describes an indirect approach to measure PTEN's lipid phosphatase
      activity in vivo. PTEN counteracts phosphatidylinositol 3-kinase action in
      dephosphorylating 3-phosphorylated phosphoinositides. Therefore, PtdIns(3,4,5)P3
      dependent activation and phosphorylation of the survival kinase Akt can be used
      as readout for cellular PTEN activity. Here we have outlined a detailed procedure
      employing a phosphoserine-specific anti-Akt antibody to examine the content of
      phosphorylated Akt by immunofluorescence and its dependence on PTEN activity.

PMID- 19160673
TI  - Analysis of phosphatidylinositol 3,4,5 trisphosphate 5-phosphatase activity by in
      vitro and in vivo assays.
AB  - Phosphatidylinositol 3,4,5 trisphosphate [PtdIns(3,4,5)P3] is a potent membrane
      bound signaling molecule transiently synthesized by phosphoinositide 3-kinase
      (PI3-kinase) in response to extracellular agonists. PtdIns(3,4,5)P3 signals need
      to be strictly controlled. PtdIns(3,4,5)P3 recruits and binds effectors that
      function in oncogenic signaling pathways. PtdIns(3,4,5)P3 activates cell
      proliferation, growth, and migration as well as regulating insulin signaling. The
      inositol polyphosphate 5-phosphatase family of enzymes dephosphorylate and
      thereby modulate PtdIns(3,4,5)P3 levels, attenuating PI3-kinase-dependent
      signaling. PtdIns(3,4,5)P3 5-phosphatase enzyme activity can be assessed in vitro
      by analysis of the hydrolysis of radiolabeled or fluorescently labeled
      PtdIns(3,4,5)P3 and in vivo by visualization of the recruitment and turnover of
      the PtdIns(3,4,5)P3-specific biosensor GFP-PH/ ARNO or other PtdIns(3,4,5)P3
      binding proteins at the plasma membrane.

PMID- 19160674
TI  - Measuring phospholipase D activity in insulin-secreting pancreatic beta-cells and
      insulin-responsive muscle cells and adipocytes.
AB  - Phospholipase D (PLD) is an enzyme producing phosphatidic acid and choline
      through hydrolysis of phosphatidylcholine. The enzyme has been identified as a
      member of a variety of signal transduction cascades and as a key regulator of
      numerous intracellular vesicle trafficking processes. A role for PLD in
      regulating glucose homeostasis is emerging as the enzyme has recently been
      identified in events regulating exocytosis of insulin from pancreatic beta-cells
      and also in insulin-stimulated glucose uptake through controlling GLUT4 vesicle
      exocytosis in muscle and adipose tissue. We present methodologies for assessing
      cellular PLD activity in secretagogue-stimulated insulin-secreting pancreatic
      beta-cells and also insulin-stimulated adipocyte and muscle cells, two of the
      principal insulin-responsive cell types controlling blood glucose levels.

PMID- 19160675
TI  - Protein kinase C as an effector of lipid-derived second messengers.
AB  - Members of the protein kinase C family are major effectors of lipid second
      messengers. We describe three protocols to assess protein kinase C activity in
      polymorphonuclear leukocytes (neutrophils). These methods are useful to study the
      activation and function of protein kinase C in these immune cells. Since
      neutrophils provide a ready source of human primary tissue, these methods are
      also useful for pharmacological studies on the protein kinase C system and for
      evaluation of protein kinase C activators and inhibitors in the context of human
      primary cells. Furthermore, since protein kinase C activity is determined by a
      number of lipid-generating signaling systems, the methods described here can also
      be employed to study the pharmacology of these "upstream" signaling systems.

PMID- 19160676
TI  - Detection of myotubularin phosphatases activity on phosphoinositides in vitro and
      ex vivo.
AB  - Phosphoinositides (PPIn) are important regulators of cellular processes like
      intracellular protein transport, cellular proliferation, apoptosis, and
      cytoskeletal organization. The amount and localization of these membrane-bound
      second messengers are regulated through a set of specific phospholipases, lipid
      kinases, and phosphatases. The elucidation of PPIn-phosphatases and their
      cellular function has gained much attention because phosphatase dysregulation is
      often associated with human genetic diseases. Our laboratory has identified the
      3'-PPIn-phosphatase myotubularin 1 (MTM1) mutated in X-linked myotubular myopathy
      (XLMTM). In addition, a whole family of myotubularin-related proteins (MTMR1
      MTMR13) has been discovered. Some of them display phosphatase activity, whereas
      for other family members no enzymatic activity could be detected. Nevertheless,
      these "dead phosphatases" myotubularins are conserved throughout evolution and
      probably exert regulatory function by heteromeric interaction with active
      phosphatase members. It was shown that MTM1 and related phosphatases act on
      PtdIns3P and PtdIns(3,5)P2; both PPIn species are important regulators of
      endocytic pathways. We describe two methods to determine phosphatase activity and
      substrate specificity of myotubularins. One is an immunoprecipitation-phosphatase
      assay, testing the activity of myotubularin immunoprecipitated from
      overexpressing cells on artificial PPIn. The other method analyzes phosphatase
      activity indirectly ex vivo in transiently transfected mammalian cells. The
      presence and subcellular localization of the myotubularin substrate PtdIns3P were
      determined using a specific binding domain (2xFYVE) produced recombinantly as a
      biosensor.

PMID- 19160677
TI  - Quantification of multiple phosphatidylinositol 4-kinase isozyme activities in
      cell extracts.
AB  - A wide spectrum of intracellular signaling events mediated by up to seven
      different phosphorylated forms of phosphatidylinositol (PtdIns) occurs in all
      eukaryotic cells. The activities of multiple, nondegenerate PI kinases and
      phosphatases control these signaling events. The PI 4-kinase isozymes account for
      the major PI kinase activity in many different cell types, and the activity of
      each isozyme is differentially regulated. The ability to measure and distinguish
      the activity of individual enzymes is therefore important and forms the subject
      of the methods in this chapter. We describe the use and application of a
      versatile radiometric assay to measuring PI 4-kinase activity in a variety of
      biochemical contexts, from purified enzymes to membrane preparations and
      permeabilized cells. Until a suitable nonradioactive reagent becomes available,
      this assay is destined to remain the most widely used method.

PMID- 19160678
TI  - Phospholipid-interacting proteins by solution-state NMR spectroscopy.
AB  - Signaling lipids are found in specific subcellular membranes, where they recruit
      and regulate cytosolic proteins and contribute to bilayer structure and dynamics.
      These interactions are vital for signaling and membrane trafficking pathways and
      contribute to the organization, growth, and differentiation of the cell. However,
      the analysis of the physical and chemical mechanisms of membrane interaction and
      lipid recognition is technically challenging, motivating the development of new
      NMR methods to study lipid and bilayer binding by peripheral membrane proteins in
      solution. We describe methods that have been optimized for the FYVE and phox (PX)
      domains of the EEA1 and Vam7p proteins, respectively, both of which specifically
      recognize phosphatidylinositol 3-phosphate (PtdIns3P) within endocytic membranes.
      Solution-state NMR methods were used to characterize the phosphoinositide and
      membrane interaction sites and affinities and can be used to illustrate
      protein:micelle structures and phospholipid specificities. The methods are
      generally applicable and can be used to discover and characterize the
      phospholipid interactions of other membrane-interacting protein domains.

PMID- 19160679
TI  - Revealing signaling in single cells by single- and two-photon fluorescence
      lifetime imaging microscopy.
AB  - Lipids are actively involved in many cellular processes. Their roles pivot toward
      determining membrane structure, compartment targeting, and membrane fusion but
      also regulation of cell signaling via their interactions with proteins and the
      production of second messengers. As they play a key role in cell signaling, the
      study of protein-protein interaction and protein conformation change in
      relationship with their interaction with lipids is of major importance. Until
      recently, the ability to detect in situ and in real time the dynamics of various
      biological events and signals without perturbing the cellular environment has
      been a real challenge. However, the emergence of fluorescence imaging of cells
      and tissues has allowed the dynamic aspects of the cell to be investigated in a
      more physiological context than the disassembled model systems employed in
      traditional biochemical analysis. This chapter highlights some of the many
      biological applications and uses of frequency- and time-domain fluorescence
      lifetime imaging microscopy (FLIM) applied to the detection of Forster resonance
      energy transfer (FRET). The first part describes a FRET system, the second part
      discusses its study by FLIM, and the third part describes the application of
      these methods to a panel of biological questions such as (1) spatio-temporal
      interaction of protein kinase B (PKB) with 3-phosphoinositide dependent protein
      kinase-1 (PDK1), (2) PKB conformation change, (3) dynamics of PKB activation, (4)
      interaction of phosphatidylinositol transfer protein (PITP) and phospholipase D
      (PLD) with lipids.

PMID- 19160680
TI  - Phosphoinositide (PI) 3-kinase assays.
AB  - The regulation of phosphoinositide (PI) 3-kinase activities has been linked to
      many normal and disease-related processes, including cell survival, cell growth
      and proliferation, cell differentiation, cell motility, and intracellular vesicle
      trafficking. However, as the family of enzymes has now grown to include eight
      true members, in three functional classes, plus several related protein kinases
      that are also inhibited by the widely used PI 3-kinase selective inhibitors,
      wortmannin and LY294002, extended methodologies are required to identify which
      type of kinase is involved in a particular cellular process, or protein complex,
      under study. A robust in vitro PI 3-kinase assay, suitable for use with
      immunoprecipitates, or purified proteins, is described here together with a
      series of modifications of substrate and assay conditions that will aid
      researchers in the identification of the particular class and isoform of PI 3
      kinase that is involved in a signaling process under investigation.

PMID- 19160681
TI  - Measurement of phosphatidylinositol and phosphatidylcholine binding and transfer
      activity of the lipid transport protein PITP.
AB  - Mammalian cells have evolved proteins that can extract single lipids from
      membranes and sequester them in their hydrophobic cavity. These proteins,
      collectively known as lipid transport proteins, play essential roles in many
      aspects of lipid metabolism, lipid signaling, and membrane traffic.
      Phosphatidylinositol transfer proteins (alpha and beta) are lipid transport
      proteins that specifically bind phosphatidylinositol or phosphatidylcholine in
      their hydrophobic cavity and facilitate their transfer from one membrane
      compartment to another. In addition, PITPbeta can facilitate sphingomyelin
      transfer. This chapter describes methods to monitor the transfer and binding
      activity of PITPs using a variety of assays, including an assay that uses
      microsomes as a donor and liposomes as an acceptor of PtdIns. For
      phosphatidylcholine and sphingomyelin transfer, liposomes are used as a donor
      compartment and mitochondria as an acceptor compartment. A separate method
      describes the use of permeabilized cells as a source of donor lipids and
      liposomes as an acceptor membrane. In addition to lipid transfer, methods to
      identify the lipids that occupy the hydrophobic cavity of PITPs are discussed.

PMID- 19160682
TI  - In vitro reconstitution of activation of PLCepsilon by Ras and Rho GTPases.
AB  - Phosphatidylinositol-specific phospholipase C (PLC) enzymes catalyze the
      hydrolysis of phophatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] to
      diacylglycerol (DAG) and inositol 1,4,5-triphosphate [Ins(1,4,5)P3]. PLCepsilon
      is a recently discovered isoform that has been shown to be activated by members
      of the Ras and Rho families of guanosine trisphosphatases (GTPases) as well as
      subunits of heterotrimeric G-proteins. We describe a method for expressing a
      truncated PLCepsilon variant as an MBP fusion protein in E. coli. Subsequently,
      we describe the methodology necessary to reconstitute this protein with K-Ras-4B
      and RhoA GTPases and measure its activation.

PMID- 19160683
TI  - Assaying endogenous phosphatidylinositol-4-phosphate 5-kinase (PIP5K) activities.
AB  - Phosphoinositides are a family of lipid second messengers interlinked by an
      extensive and highly regulated network of kinases and phosphatases. The
      modulation of phosphoinositide profiles can regulate numerous cancer-related
      pathways, including cell survival, cell proliferation, migration, integrin
      activation, and transcription. PtdIns(4,5)P2 is at the heart of phosphoinositide
      signaling; its levels are controlled by enzymes that synthesize it and those that
      degrade it. Phosphatidylinositol-4-phosphate 5-kinases (PIP5 K) phosphorylate
      PtdIns4P on the 5-position and constitute the major pathway for the generation of
      PtdIns(4,5)P2. We will discuss how to suppress the expression of human PIP5 Kbeta
      using RNAi and how to measure the activity and levels of the endogenous enzyme.
      We describe a method to immunoprecipitate the endogenous PIP5 Kbeta and to assay
      its activity. Western blotting with another panel of antibodies is then used to
      determine the levels of endogenous PIP5 Kbeta in the immunoprecipitates.

PMID- 19160685
TI  - Board retreat builds leader unity, keeps organization on mission.

PMID- 19160684
TI  - Preparation of membrane rafts.
AB  - The concept that biological membranes contain microdomains of specialized lipid
      and protein composition has attracted great attention in recent years. Initially,
      the focus in the field was very much on the characterization of cholesterol-and
      sphingolipid-rich plasma membrane microdomains that were resistant to
      solubilization in the cold non-ionic detergent Triton X-100. Such detergent
      insoluble membrane domains were of low buoyant density and could be readily
      purified on sucrose equilibrium density gradients. The intrinsic buoyancy of the
      detergent-insoluble domains gave rise to the term "lipid rafts." Cholesterol- and
      sphingolipid-rich rafts at the plasma membrane have been implicated in a wide
      range of cellular processes, including pathogen invasion, receptor signaling, and
      endocytosis. However, work with other non-ionic detergents such as Lubrol WX and
      Brij-98 has revealed the existence of various raft subtypes with differing lipid
      compositions and proposed functions. More recently, there has been some focus on
      isolating lipid rafts from intracellular organelles, in particular membranes from
      the Golgi-endosomal pathway, where raft lipids have been proposed to function in
      processes such as the sorting of vesicular cargo and the processing of amyloid
      precursor protein. While there remains a large degree of controversy surrounding
      the purity, the physiological importance, and even the existence of different
      types of lipid rafts in intact cells, the ability to routinely purify such
      domains has led to significant progress in understanding the functional
      architecture of biological membranes. We describe a number of widely used methods
      to prepare rafts, based on early preparations of caveolae by density gradient
      ultracentrifugation and immunoaffinity precipitation.

PMID- 19160686
TI  - Today's EMR is not the answer for most practices.

PMID- 19160687
TI  - Avoiding the pitfalls of Medicare's 'incident-to' rules.

PMID- 19160688
TI  - Cultivating physician leaders.

PMID- 19160689
TI  - Who's measuring your group's quality?

PMID- 19160690
TI  - Revenue cycle rewind.

PMID- 19160691
TI  - How do you develop a governance system for a growing practice?

PMID- 19160692
TI  - Shopping for SIZE. Should you purchase another practice to enlarge your own?
AB  - To buy or not to buy: That's the question to answer as you secure your
      organization's place in the market.

PMID- 19160693
TI  - How does your practice grow? The rationale for expansion.
AB  - If the benefits are so clear, why do so many medical groups and academic
      departments struggle with the decision to add new physicians?

PMID- 19160694
TI  - Delight is in the details. How you can add 'patient pleasers' to your practice.
AB  - Letting your patients know that little things matter can pay dividends in patient
      loyalty--as well as to the bottom line.

PMID- 19160695
TI  - Thirty-five years of noninvasive bladder carcinoma: a plea for the use of
      papillary intraurothelial neoplasia as new terminology.
AB  - Since the introduction of the World Health Organization (WHO) 1973 terminology
      for bladder cancer, noninvasive epithelial bladder tumors have consistently been
      labeled bladder carcinomas. In the WHO 2004 classification the removal of the
      "carcinoma" label from a small subset of noninvasive bladder carcinomas with
      indolent behavior created the entity of papillary urothelial neoplasms of low
      malignant potential, but the remaining noninvasive carcinomas of the urothelial
      tract retained this label. In this overview, we analyze clinical, pathologic and
      molecular-genomic findings to support a more evidence-based nomenclature of
      papillary neoplastic lesions of the urinary tract. In line with the tendency
      during the last few decades to label flat precancerous lesions of various organs
      intraepithelial neoplasms, we may now also refer to dysplasia and carcinoma in
      situ of the urinary tract as low and high grade intraurothelial neoplasia,
      respectively. To harmonize nomenclature, we now propose that the terms low and
      high grade papillary urothelial carcinoma be replaced by low and high grade
      papillary intraurothelial neoplasiafor all noninvasive urothelial cancers.

PMID- 19160696
TI  - Actinic damage in histopathologically normal skin.
AB  - OBJECTIVE: To establish measures of sun damage in histopathologically normal
      skin. STUDY DESIGN: Biopsies were taken from the upper inner arm, representing
      skin with presumably minimum sun exposure, from skin of the forearm with no
      visible sun damage, from skin of the forearm with visible sun damage and from
      normal-appearing skin from the forearm of individuals who had sun exposure that
      had resulted in actinic keratosis (AK) lesions. In addition, a data set of nuclei
      from AKs was recorded. RESULTS: In histopathologically normal skin, monotonically
      increasing damage was observed in individuals with increased exposure to solar
      radiation. CONCLUSION: Karyometry can detect and statistically secure changes in
      skin due to solar exposure at a stage at which the skin is histopathologically
      determined to be normal.

PMID- 19160697
TI  - Texture- and object-related automated information analysis in histological still
      images of various organs.
AB  - OBJECTIVE: To create algorithms and application tools that can support routine
      diagnoses of various organs. MATERIALS: A generalized algorithm was developed
      that permits the evaluation of diagnosis-associated image features obtained from
      hematoxylin-eosin-stained histopathologic slides. The procedure was tested for
      screening of tumor tissue vs. tumor-free tissue in 1,442 cases of various organs.
      Tissue samples studied include colon, lung, breast, pleura, stomach and thyroid.
      The algorithm distinguishes between texture- and object-related parameters.
      Texture-based information-defined as gray value per pixel measure--is independent
      from any segmentation procedure. It results in recursive vectors derived from
      time series analysis and image features obtained by spatial dependent and
      independent transformations. Object-based features are defined as gray value per
      biologic object measured. RESULTS: The accuracy of automated crude classification
      was between 95% and 100% based upon a learning set of 10 cases per diagnosis
      class. Results were independent from the analyzed organ. The algorithm can also
      distinguish between benign and malignant tumors of colon, between epithelial
      mesothelioma and pleural carcinomatosis or between different common pulmonary
      carcinomas. CONCLUSION: Our algorithm distinguishes accurately among crude
      histologic diagnoses of various organs. It is a promising technique that can
      assist tissue-based diagnosis and be expanded to virtual slide evaluation.

PMID- 19160698
TI  - Role of molecular markers in diagnosis and prognosis of renal cell carcinoma.

PMID- 19160699
TI  - Utility of prostate biopsy morphometric sum optical density for identifying
      extraprostatic extension on subsequent prostatectomy.

PMID- 19160700
TI  - Is it time for a new bladder neoplasms classification?

PMID- 19160701
TI  - Histone acetylation and chromatin pattern in cancer: a review.

PMID- 19160702
TI  - Renal cell carcinoma: molecular and genetic markers as new prognostic and
      therapeutic tools.

PMID- 19160703
TI  - Computer-assisted nuclear morphometry in relation to metastasis to regional lymph
      nodes in canine hepatoid adenocarcinomas.

PMID- 19160704
TI  - Karyometric changes of intrafusal muscle fibers in neuromuscular diseases.

PMID- 19160705
TI  - Military programs accredited?

PMID- 19160706
TI  - Liver-function testing.

PMID- 19160707
TI  - NT-proBNP: improved standard in CHF diagnosis.

PMID- 19160708
TI  - Binding site's CEO traces history of success.

PMID- 19160709
TI  - Theft in the lab.

PMID- 19160710
TI  - Where the wild things are. Interview by Carren Bersch.

PMID- 19160711
TI  - A re-energized debate on stem cells.

PMID- 19160712
TI  - Direct-access testing: issues and opportunities. Insights on DAT compared to
      physician-ordered lab tests.

PMID- 19160713
TI  - Meta-analysis under the looking glass: post-menopausal hormone replacement
      therapy.

PMID- 19160714
TI  - Pharmacotherapy of epilepsy: state of the art and developments.
AB  - PURPOSE: A discussion of modern day practice and new developments in
      antiepileptic drug treatment. CONTENTS: Important principles of antiepileptic
      therapy are addressed--starting with antiepileptic drug therapy, pharmacokinetics
      and pharmacodynamics, therapeutic drug monitoring, drug-induced adverse effects
      and the withdrawal of antiepileptic drugs. Furthermore, the pathophysiology of
      focal and generalized epilepsies and the mechanism of action of several
      antiepileptic drugs are briefly reviewed. Modern treatment algorithms for
      different types of epileptic seizures are presented. A significant development is
      the introduction of new antiepileptic drugs and particularly of those drugs that
      have been developed according to the latest insights into pathophysiology. Also
      of interest is the increased focus on adverse effects and on quality of life.
      Partly due to these developments, combining antiepileptic drugs has received
      renewed attention in an attempt to maintain effective seizure control but with a
      reduction of adverse effects.

PMID- 19160715
TI  - A patient compliance survey in a general medical clinic.
AB  - OBJECTIVE: To examine the level of compliance with regard to the administration
      of medications in a general medical clinic of a regional teaching hospital in
      Hong Kong. METHOD: Patients who had been taking the prescribed medications for
      the last 12 months and who had received their prescriptions from the clinic
      pharmacy during their last visit were interviewed. The level of drug compliance
      was measured. Patients who had greater than one-tenth of the drug supply
      remaining from last visit were considered to be non-compliant, those who had less
      than one-tenth of the total drug supply but did not adhere to the regimen were
      considered to be partially compliant, and patients who took 90% or more of their
      prescribed medications were considered to be compliant. RESULTS: Of the 61
      patients interviewed, 12 (19.7%) were non-compliant and 21 (34.4%) were partially
      compliant. Reasons for poor treatment compliance included appearance or worsening
      of symptoms during therapy, disappearance of symptoms, concomitant medications
      from other physicians, forgetfulness due to lifestyle factors, working conditions
      or complexity of regimen. Five (8.2%) patients had visited other doctors since
      their last hospital clinic visit, but most of them did not inform these doctors
      about their regular medications. CONCLUSION: In this pilot study, 50% of patients
      on long-term medical therapy (at least 12 months) were non-compliant or only
      partially compliant. Apart from drug wastage and sub-optimal patient care,
      apparent treatment failure may lead to inappropriate increase in dosage, addition
      of another medication or change to a more potent or expensive preparation.
      Failure of patients to inform other doctors about their therapy may also result
      in duplicative therapy, drug interactions and more drug wastage. Pharmacists
      should take an active role to educate patients about the appropriate use of drugs
      and reinforce treatment compliance.

PMID- 19160716
TI  - Pyrogen testing of lipid-based TPN using Mono Mac 6 monocyte cell line and
      DELFIA.
AB  - OBJECTIVE: Measurement of lipopolysaccharide (LPS) induced interleukin-6 (IL-6)
      secretion in Mono Mac 6 cells. METHOD: Dissociation-enhanced lanthanide fluoro
      immunoassay (DELFIA), a technique based on time-resolved fluorescence. RESULTS: A
      comparison of DELFIA and the B9 bioassay showed a correlation between the results
      of the two assays. DELFIA did not show any crossreactivity with the human
      cytokines TNFalpha, IL-1beta, IL-1alpha, IL-2, IL-4, IFNgamma, murine IL-6 or
      LPS. In aqueous solution the detection limit was 2.5 pg LPS/ml, and in a 25%
      dilution of a lipid-based total parenteral nutrition (TPN) product it was 25 pg
      LPS/ml. TPN did not interfere with the DELFIA assay, but the IL-6 secretion from
      the Mono Mac 6 cells was inhibited at TPN concentrations above 25%. CONCLUSION: A
      combination of Mono Mac 6 cells with DELFIA was found to be a reliable method for
      detecting LPS, but further validation by independent laboratories is justified.

PMID- 19160717
TI  - Thrombolytics--a drug utilization review in a district general hospital.
AB  - BACKGROUND: Retrospective drug utilization review (DUR) can be of benefit in
      determining the extent to which recommendations derived from clinical trials are
      carried out in practice. OBJECTIVE: To determine whether thrombolysis was given
      in accordance with hospital guidelines. METHOD: A retrospective DUR of the
      treatment of patients with a diagnosis of myocardial infarction (MI) admitted to
      Borders General Hospital during April-December 1993 was carried out. RESULTS:
      Forty-eight per cent of these patients received thrombolysis, representing 52% of
      all patients with a definite diagnosis of MI. The most frequent reason for
      thrombolysis not being given was atypical presentation, particularly ECG changes
      not in accordance with those described in the hospital guidelines for diagnosis
      of MI. Contraindications and late presentations were very few in number.
      Appropriate reasons were identified for all patients who did not receive
      thrombolytic therapy. Mortality both at discharge and at 6 months was slightly
      greater in these patients than in treated patients. CONCLUSION: Thombolytic drugs
      were used in line with the hospital guidelines in most cases, although there was
      no identifiable reason for the use of alteplase instead of streptokinase in two
      cases.

PMID- 19160718
TI  - Stability of admixtures of pethidine and metoclopramide in aqueous solution, 5%
      dextrose and 09% sodium chloride.
AB  - OBJECTIVE: To study the stability of admixtures of pethidine and metoclopramide
      in aqueous solution, 0.9% sodium chloride and 5% dextrose preparations. METHOD:
      Aqueous mixtures of 1 ml of 50 mg/ml pethidine with 2ml of 5 mg/ml metoclopramide
      were prepared in plastic syringes, while the 0.9% sodium chloride and 5% dextrose
      admixtures, each containing 7.35 mg/ml of pethidine and 0.15 mg/ml of
      metoclopramide, were prepared in infusion bags. The preparations were stored
      under light and dark conditions at 32 degrees C for 48 h. Samples were collected
      at 0, 0.5, 1, 2, 4, 6, 8, 24, 32 and 48 h. A high-performance liquid
      chromatographic method was developed to separate and quantify both drugs.
      RESULTS: All preparations were found to be physically and chemically stable for
      at least 48h, as concentration changes were within 10% of their initial level,
      with no development of haze, precipitate or colour. Light appeared to have a
      negligible effect. Although pH changes were observed, they were inconsistent and
      were within the ranges in which the drugs are expected to remain stable.
      Pethidine and metoclopramide admixtures can, therefore, on stability grounds be
      used for the concomitant management of pain, nausea and vomiting.

PMID- 19160719
TI  - Determination of kinetic parameters for prothrombin complex activity during
      initiation of anticoagulation.
AB  - OBJECTIVE: A prospective determination of the kinetic parameters of prothrombin
      complex activity (PCA) during initiation of anticoagulation in seven adult
      patients (4 males and 3 females, age 62.9 +/- 5.8 years, mean SD) receiving
      anticoagulant therapy with warfarin. METHOD: All excluding one patient received a
      fixed daily dose of 5mg warfarin over an initial 3 days. Three successive daily
      doses of warfarin were recorded, together with the corresponding PCA. The kinetic
      parameters for elimination of PCA during the initiation of anticoagulation were
      estimated from the log PCA-time plot with a 1-compartment model. RESULTS: The
      mean elimination rate constant (kp) of PCA was 0.377 day(-1) (range 0.242-0-588
      day (-1)) during initiation of anticoagulation. The coefficient of variation in
      kp was about 28%, indicating the considerable inter-individual differences in PCA
      response to warfarin. The mean plasma half-life of PCA was 1.96 days. There were
      no significant relationships (by simple regression analysis) between kp and
      cumulative warfarin doses per kg of body weight or age during initiation of
      anticoagulation. CONCLUSION: The results suggest that for a 50% reduction of PCA,
      one would need about 2 days after initiation of anticoagulation.

PMID- 19160720
TI  - Long-term stability of vancomycin hydrochloride in intravenous infusions.
AB  - BACKGROUND AND OBJECTIVE: Vancomycin is often used in antibiotic infusions for
      hospitalized patients and it is advantageous to prepare such intravenous
      solutions in advance. The objective of this study was to investigate the long
      term stability of this antibiotic stored at 4 degrees C in polyvinyl chloride
      (PVC) bags. METHOD: Five bags each of 0.5 or 1 g vancomycin hydrochloride per 100
      ml of 5% dextrose were studied for 2 months by high-performance liquid
      chromatography, visual inspection and pH measurement. RESULTS: No colour change
      or precipitation was observed. The pH values of the preparations increased
      significantly over the period of study without influencing the antibiotic
      concentration. Based on a shelf-life of 90% residual potency, the vancomycin
      solutions were stable for at least 58 days at 4 degrees C. CONCLUSION: From a
      chemical stability viewpoint, the antibiotic may be prepared in advance by a
      centralized intravenous admixture service for use within the limits described.

PMID- 19160721
TI  - Interrelationships of quality of life, compliance, clinical outcomes and life
      satisfaction: a cross-sectional study on hypertensive geriatrics.
AB  - OBJECTIVE: (i) To assess quality of life (QoL) profiles in hypertensive
      geriatrics with SF-36; (ii) to assess the compliance of geriatrics to
      medications; (iii) to estimate clinical outcomes (reduction in systolic and
      diastolic blood pressure); (iv) to assess life satisfaction and (v) to explore
      the interrelationships of QoL, compliance, clinical outcomes and life
      satisfaction in hypertensive geriatrics. METHOD: Fifty-nine hypertensive
      geriatric patients in cardiology and 65 Plus clinics in West Virginia Hospitals
      were studied. RESULTS: Age showed a significant negative correlation with
      physical functioning (r = 0.339, P< or =0.0127) and physical role (r=0.335, P< or
      =0.0148). The physical role facet of SF-36 is correlated with life satisfaction
      in geriatrics (r = 0.316, P < or =0.0219). A regression analysis (backward
      stepwise) not including bodily pain (BP) and general health (GH) resulted in a
      model explaining 22.3% of variance (n = 54, F = 2.252, P < or = 0.0543). Physical
      role (P < or = 0.0084) and mental health facets (P< or = 0.0184) of SF-36 emerged
      as the predictors of life satisfaction in elderly hypertensive patients.
      Emotional role functioning (P < or = 0.0257) and social functioning (P < or =
      0.0033) scores predicted levels of diastolic blood pressure in elderly
      hypertensive patients. However, all eight concepts of SF-36 failed to predict
      compliance behaviour in geriatrics (n = 53, P < or = 0.6913, R2= 0.110).

PMID- 19160722
TI  - Effect of metoprolol and amlodipine on myocardial total ischaemic burden in
      patients with stable angina pectoris.
AB  - OBJECTIVE: A randomized double-blind cross-over study to assess the effect on
      myocardial total ischaemic burden and the anti-anginal efficacy of the beta-1
      blocker metoprolol given as metoprolol CR/Zok versus the calcium channel blocker
      amlodipine, both given in the recommended and commonly used doses of 100 mg o.d.
      and 5 mg o.d., respectively. METHOD: Fifty-two patients with a history of stable
      exercise-induced angina pectoris and at least six episodes of significant ST
      segment depression during 24-h ambulatory electrocardiographic monitoring after 9
      days of placebo were included in the study. The patients first completed a 9-day
      placebo run-in phase with additional administration of a long-acting nitrate
      during the first 7 days. They then received in a randomized sequence metoprolol
      CR/Zok and amlodipine each for 4 weeks. During placebo treatment and at the end
      of each phase of active treatment the patients' clinical progress was assessed
      and a 24-h ECG monitor performed. RESULTS: Forty-seven patients completed the two
      4-week treatment periods. Five patients withdrew from the study. The number of
      ischaemic episodes during 24 h was 30.4 at baseline with placebo, which was
      reduced significantly by both treatments (P<0.005) to 6.8 episodes after
      metoprolol and 15.8 episodes after amlodipine treatment (P<0.001 for the
      difference between the treatment groups). Metoprolol and amlodipine reduced the
      total duration of ischaemic episodes from 86.0 min to 15-1 and 48.3 min with a
      mean episode duration of 1.1 and 2.6 min, respectively. Twenty patients on
      metoprolol (42.6%) and four on amlodipine (8.4%) showed no ST-segment depression
      at the end of treatment. Baseline heart rate of 80 b.p.m. decreased by 11.1
      b.p.m. after metoprolol and increased by 4b.p.m. after amlodipine. Anginal
      attacks were reduced from 14.8 attacks per week at baseline to 2.4 attacks on
      metoprolol and 4.4 attacks on amlodipine treatment. For all variables the
      observed changes from baseline were significant after either treatment (P<0.005)
      with a significantly more pronounced effect in favour of metoprolol (P<0.0001).
      Ten patients reported nine different adverse events during metoprolol treatment.
      On amlodipine, 12 patients were affected by 11 different symptoms leading to
      three treatment withdrawals. On metoprolol one patient withdrew due to adverse
      events. CONCLUSION: Both drugs reduce total ischaemic burden by reducing
      ischaemic episodes and antianginal attacks, with a significantly greater effect
      from metoprolol 100 mg o.d. as compared to amlodipine 5 mg o.d.

PMID- 19160723
TI  - Prescription of statins: cost implications of evidence-based treatment applied to
      a health authority population.
AB  - OBJECTIVE: To examine the amount spent on cardiovascular drugs and coronary
      services in one health authority and to estimate the cost of translating recent
      trial evidence for HMG-CoA reductase inhibitors (statins) into clinical practice.
      METHOD: Prescription and hospital activity data over a 2-year period were
      analysed retrospectively for 449 834 patients of 89 general medical practices.
      The average annual amount spent on these patients was calculated for eight
      cardiovascular drug groups defined in the British National Formulary (BNF),
      hospitalizations for ischaemic heart disease, and revascularization and
      angiography procedures. The proportion of the study population with the potential
      to benefit from treatment with statins was then determined by identifying
      individuals with the characteristics of participants who benefited in any one of
      three published clinical trials. Identification of these individuals was assisted
      by the use of population-specific morbidity data and serum cholesterol levels
      reported in published surveys. RESULTS: The actual average annual expenditure on
      statins (pound 774 per 1000 patients registered) was lower than that on ACE
      inhibitors, beta-adrenoceptor blockers, calcium channel blockers, diuretics and
      nitrates and was less than one-tenth of the combined annual cost of all coronary
      hospitalizations examined. In the patient population studied it was estimated
      that 7547 (1.7%) individuals would be eligible for secondary prevention with
      statins whilst 20406 (4.5%) would be eligible for primary prevention. After
      adjusting for possible non-adherence, the estimated annual cost of statin
      treatment for all such individuals was calculated to be between pound 22 599 and
      pound 28 413 per 1000 of the study population. Application of these figures to
      the registered population of the health authority would add approximately pound
      11.8 million to a pound 60 million primary and secondary care drugs budget. It is
      proposed that statin treatment will have to be prioritized for those at highest
      risk, whilst maintaining a population-based strategy of promoting lifestyle
      advice to reduce the risk of cardiovascular events.

PMID- 19160724
TI  - Case-controlled review of Clostridium difficile-associated diarrhoea in southern
      Tasmania.
AB  - AIM: While the incidence of Clostridium difficile-associated diarrhoea (CDAD) has
      increased sharply over the last 15 years, its risk factors are still not well
      defined. The aim of this study was to review cases of CDAD at the major teaching
      hospital in Tasmania, Australia, to identify risk factors for CDAD and their
      association with prognosis. METHODS: A retrospective review of the medical
      records of adult patients admitted to the hospital between January 1994 and
      December 1996 was performed. Sixty-four patients who developed CDAD prior to or
      during their admission, and an additional 120 diarrhoea-free patients (the
      control group) were studied. An extensive range of demographic and clinical
      variables were recorded, and the differences between the control group and
      patients with CDAD were evaluated. RESULTS: The CDAD patients had a median age of
      66 years (range 22-95 years), with females accounting for 52% of cases. There
      were no significant demographic differences from the control group. Identifiable
      risk factors for developing CDAD were severe underlying disease, renal
      impairment, exposure to antibiotics or antineoplastic agents, and the use of
      total parenteral nutrition or nasogastric feeding. Cephalosporins were the most
      frequently used antibiotics in both CDAD and control patients, with cefotaxime
      being the only antibiotic which was identified as being significantly associated
      with an increased risk of CDAD. The median length of diarrhoea episodes was 9
      days (range 1-60 days). The mortality rate was 17.2%, and factors associated with
      a poor prognosis were older age, severe underlying disease, renal impairment and
      failure to treat with metronidazole or vancomycin. Delay in starting specific
      treatment and use of codeine were related to prolonged CDAD. CONCLUSION: CDAD is
      a growing contributor to hospital morbidity and costs. Severely ill patients with
      compromised immune function are particularly susceptible, with antibiotic use
      being a major risk factor. Prompt diagnosis and initiation of treatment are
      important factors in the improvement of prognosis.

PMID- 19160725
TI  - Determination of phenobarbitone population clearance values for physically and
      mentally handicapped Chinese children with epilepsy.
AB  - OBJECTIVE: To estimate population clearance values of phenobarbitone in epileptic
      children of Chinese origin in Hong Kong. METHOD: Steady-state concentration data
      were gathered during routine care at a special chronic centre for the physically
      and mentally handicapped. Age, gender, body weight and concurrent medication
      (taking additional carbamazepine (CBZ) or phenytoin (PTO)) were the four fixed
      effects tested simultaneously for their influence on the population mean of
      phenobarbitone clearance, using the nonlinear mixed-effects model. RESULTS: No
      age or gender-related effect was found. Both body weight and concurrent
      medication were the important determinants of phenobarbitone clearance. The
      population mean values of phenobarbitone clearance obtained were 0.250
      litres/day/kg for children on phenobarbitone only and 0.208 litres/day/ kg for
      those on concomitant CBZ or PTO. Their corresponding interindividual and
      intraindividual variability values were 34.9% and 15.1% for mono-pharmacy and
      29.3% and 7.84% for polypharmacy patient groups. CONCLUSION: The correlation
      between phenobarbitone clearance and body weight found may allow dosage
      adjustment to be made to achieve target steady-state plasma concentrations.

PMID- 19160726
TI  - Stability of morphine sulphate in saline under simulated patient administration
      conditions.
AB  - OBJECTIVE: To study the stability of morphine sulphate solutions under simulated
      administration conditions in a patient-controlled analgesic device. METHOD:
      Concentrations of 1 mg/ml and 10 mg/ml morphine sulphate in saline were monitored
      over 16 days under slow continuous delivery from Deltec Medication cassettes kept
      in the dark at a controlled temperature of 32 degrees C and a humidity between 36
      and 38%. The morphine concentrations in the samples, collected at 0, 1, 2, 5, 6,
      7, 9, 12, 14 and 16 days, were measured by a stability indicating high
      performance liquid chromatographic method. RESULTS: Throughout the study period,
      the reservoir concentrations varied within 10% of their initial values and there
      was no chromatographic evidence of degradation. However, the pH of both
      reservoirs decreased with time, but morphine is expected to be stable within the
      observed pH range. CONCLUSION: This study demonstrated that the concentrating
      effect due to evaporation under the storage conditions described, over 16 days,
      was not of significance and the product was stable.

PMID- 19160727
TI  - The effects of gentamicin and vitamin E on enzymatic antioxidant defence in
      guinea-pig lung.
AB  - OBJECTIVE: To study the possible effects of gentamicin on the enzymic free
      radical defence system in the lung. METHOD: Activities of cytoplasmic superoxide
      dismutase (CuZn-SOD), mitochondrial superoxide dismutase (Mn-SOD), glutathione
      peroxidase (GSH-Px) and catalase (CAT) enzymes were studied in lung tissues from
      gentamicin-treated guinea-pigs compared to controls. RESULTS: Levels of those
      enzymes were higher in the gentamicin group except for xanthine oxidase (XO)
      activity. Vitamin E given concomitantly with gentamicin caused significant
      decreases in CuZn-SOD, Mn-SOD and GSH-Px activities but an increase in CAT
      activity in the lung tissue. Only vitamin treatment caused significant decreases
      in the activities of CuZn-SOD, Mn-SOD and GSH-Px enzymes and an increase in CAT
      activity. CONCLUSION: The results suggest that lung tissue is able to respond
      quickly and effectively against the adverse effects of some oxidant substances by
      inducing and/or activating the enzymatic free-radical defence system.

PMID- 19160728
TI  - Drug use evaluation of ciprofloxacin: impact of educational efforts on
      appropriateness of use.
AB  - OBJECTIVE: To evaluate the appropriateness of ciprofloxacin use in a 550-bed
      general hospital before and after an educational intervention. METHOD: A drug use
      evaluation was carried out for 6 weeks, to examine the appropriateness of
      initiating therapy with ciprofloxacin, as judged by compliance with the
      hospital's protocols for antibiotic use. The results were distributed to all the
      hospital physicians, together with a review of the usage guidelines. Four months
      later the survey was repeated to examine the effects of this educational effort
      on the patterns of use. RESULTS: During the initial survey, 115 patients were
      treated with ciprofloxacin. During the follow-up 126 patients were treated with
      ciprofloxacin. The percentage of unjustified use had decreased from 31% to 13% at
      follow-up (P<0.005). Improvement was seen in all the hospital departments needing
      improvement and most significantly in the medical departments. The most frequent
      indication for use of the drug was urinary tract infection (86 patients (36%) in
      total in the two stages). The most significant improvement was in justified usage
      for urinary tract infections: from 65% in the initial stage to 88% in the second
      stage (P < 0.025). CONCLUSION: This study indicates that performing a drug use
      evaluation and distributing the results to the doctors concerned has a beneficial
      effect on the appropriateness of drug use and provides an important tool for
      identifying the main problems in prescribing, so that educational efforts can be
      focused.

PMID- 19160729
TI  - On framing the research question and choosing the appropriate research design.
AB  - Clinical epidemiology is the science of human disease investigation with a focus
      on diagnosis, prognosis, and treatment. The generation of a reasonable question
      requires the definition of patients, interventions, controls, and outcomes. The
      goal of research design is to minimize error, ensure adequate samples, measure
      input and output variables appropriately, consider external and internal
      validities, limit bias, and address clinical as well as statistical relevance.
      The hierarchy of evidence for clinical decision making places randomized
      controlled trials (RCT) or systematic review of good quality RCTs at the top of
      the evidence pyramid. Prognostic and etiologic questions are best addressed with
      longitudinal cohort studies.

PMID- 19160730
TI  - Longitudinal studies and determination of risk.
AB  - Longitudinal and observational study designs are important methodologies to
      investigate potential associations that may not be amenable to RCTs. In many
      cases, they may be performed using existing data and are often cost-effective
      ways of addressing important questions. The major disadvantage of observational
      studies is the potential for bias. The absence of randomization means that one
      can never be certain that unknown confounders are present, and specific studies
      designs have their own inherent forms of bias. Careful study design may minimize
      bias. Establishing a casual association based on observational methods requires
      due consideration of the quality of the individual study and knowledge of its
      limitations.

PMID- 19160731
TI  - Modeling longitudinal data, I: principles of multivariate analysis.
AB  - Statistical models are used to study the relationship between exposure and
      disease while accounting for the potential role of other factors' impact on
      outcomes. This adjustment is useful to obtain unbiased estimates of true effects
      or to predict future outcomes. Statistical models include a systematic component
      and an error component. The systematic component explains the variability of the
      response variable as a function of the predictors and is summarized in the effect
      estimates (model coefficients). The error element of the model represents the
      variability in the data unexplained by the model and is used to build measures of
      precision around the point estimates (confidence intervals).

PMID- 19160732
TI  - Modeling longitudinal data, II: standard regression models and extensions.
AB  - In longitudinal studies, the relationship between exposure and disease can be
      measured once or multiple times while participants are monitored over time.
      Traditional regression techniques are used to model outcome data when each
      epidemiological unit is observed once. These models include generalized linear
      models for quantitative continuous, discrete, or qualitative outcome responses
      and models for time-to-event data. When data come from the same subjects or group
      of subjects, observations are not independent and the underlying correlation
      needs to be addressed in the analysis. Under these circumstances, extended models
      are necessary to handle complexities related to clustered data and repeated
      measurements of time-varying predictors or outcomes.

PMID- 19160733
TI  - The design of randomized controlled trials.
AB  - Today's clinical practice relies on the application of well-designed clinical
      research, the gold standard test of an intervention being the randomized
      controlled trial. Principles of the randomized controlled trial include emphasis
      on the principal research question, randomization, and blinding; definitions of
      outcome measures, inclusion and exclusion criteria, and comorbid and confounding
      factors; enrolling an adequate sample size; planning data management and
      analysis; preventing challenges to trial integrity, such as dropout, drop-in, and
      bias. The application of pretrial planning is stressed to ensure the proper
      application of epidemiological principles, resulting in clinical studies that are
      feasible and generalizable. In addition, funding strategies and trial team
      composition are discussed.

PMID- 19160734
TI  - Analysis of randomized controlled clinical trials.
AB  - When analyzing the results of a trial, the primary outcome variable must be kept
      in clear focus. In the analysis plan, consideration must be given to comparing
      the characteristics of the subjects, taking account of differences in these
      characteristics; intention-to-treat analysis; interim analyses and stopping
      rules; mortality comparisons; composite outcomes; research design including run
      in periods, factorial, stratified, and crossover designs; number needed to treat;
      power issues; multivariate modeling; and hypothesis-generating analyses.

PMID- 19160735
TI  - Evaluation of diagnostic tests.
AB  - As technology advances, diagnostic tests continue to improve, and each year, we
      are presented with new alternatives to the standard procedures. Given the
      plethora of diagnostic alternatives, diagnostic tests must be evaluated to
      determine their place in the diagnostic armamentarium. Criteria include
      sensitivity and specificity, positive and negative predictive values, likelihood
      ratios for positive and negative tests, and receiver operating characteristic
      curves. The prevalence of disease influences the diagnostic utility of tests,
      particularly when diseases are rare or very frequent.

PMID- 19160736
TI  - Biomarkers and surrogates in clinical studies.
AB  - Biomarkers are defined as anatomic, physiologic, biochemical, molecular, or
      genetic parameters associated with the presence, absence, or severity of a
      disease process. As such, biomarkers may be useful as prognostic and diagnostic
      tests. Establishing the utility of a given biomarker as a prognostic or
      diagnostic test requires the conduct of carefully designed cohort studies in
      which the biomarker and the outcome of interest are measured independently. The
      design and analysis of such studies is discussed. Surrogate outcomes in clinical
      trials consist of events or biomarkers intended to reflect important clinical
      outcomes. Surrogate outcomes may offer advantages in providing statistically
      robust estimates of treatment effects with smaller sample sizes. However, to be
      useful, surrogate outcomes have to be validated to ensure that the effect of
      therapy on them truly reflects the effect of therapy on the important clinical
      outcomes of interest.

PMID- 19160737
TI  - Measurement and analysis of patient-reported outcomes.
AB  - The study of patient-reported outcomes, now common in clinical research, had its
      origins in social and scientific developments during the latter 20th century.
      Patient-reported outcomes comprise functional and health status, health-related
      quality of life, and quality of life. The terms overlap and are used
      inconsistently, and these reports of experience should be distinguished from
      expressions of preference regarding health states. Regulatory standards from the
      United States and the European Union provide some guidance regarding reporting of
      patient-reported outcomes. The determination that measurement of patient-reported
      outcomes is important depends in part on the balance between subjective and
      objective outcomes of the health problem under study. Instrument selection
      depends to a large extent on practical considerations. A number of instruments
      can be identified that are frequently used in particular clinical situations. The
      domain coverage of commonly used generic short forms varies substantially.
      Individualized measurement of quality of life is possible, but resource
      intensive. Focus groups are useful, not only for scale development but to confirm
      the appropriateness of existing instruments. Under classical test theory,
      validity and reliability are the critical characteristics of tests. Under item
      response theory, validity remains central, but the focus moves from the
      reliability of scales to the relative levels of traits in individuals and items'
      relative difficulty. Plans for clinical studies should include an explicit model
      of the relationship of patient-reported outcomes to other parameters, as well as
      definition of the magnitude of difference in patient-reported outcomes that will
      be considered important. Prevention of missing patient-reported outcome data is
      particularly important; to a limited extent, a variety of statistical techniques
      can mitigate the consequences of missing data.

PMID- 19160738
TI  - Bias in clinical studies of genetic diseases.
AB  - Clinical epidemiological research in genetic diseases entails the assessment of
      phenotypes, the burden and etiology of disease, and the efficacy of preventive
      measures or treatments in populations. In all areas, the main focus is to
      describe the relationship between exposure and outcome and determine one of the
      following: prevalence, incidence, cause, prognosis, or effect of treatment. The
      accuracy of these conclusions is determined by the validity of the study.
      Validity is determined by addressing potential biases and possible confounders
      that may be responsible for the observed association. Therefore, it is important
      to understand the types of bias that exist and be able to assess their impact on
      the magnitude and direction of the observed effect. This chapter reviews the
      epidemiological concepts of selection bias, information bias, and confounding and
      discusses ways in which these sources of bias can be minimized.

PMID- 19160739
TI  - Genetic epidemiology of complex phenotypes.
AB  - Genetic factors play a substantive role in the susceptibility to common diseases.
      Due to recent advancements in the characterization of genetic variants and large
      scale genotyping platforms, multiple genes have now been identified for common,
      complex diseases. As a result, there is an immense interest in elucidating
      genetic factors in complex traits. Therefore, it is important to understand the
      design as well as the technical and statistical issues of the two most common
      approaches for gene identification: linkage and association.

PMID- 19160740
TI  - Qualitative research in clinical epidemiology.
AB  - This chapter has been written to specifically address the usefulness of
      qualitative research for the practice of clinical epidemiology. The methods of
      grounded theory to facilitate understanding of human behavior and construction of
      monitoring scales for use in quantitative studies are discussed. In end-stage
      renal disease patients receiving long-term hemodialysis, a qualitative study used
      grounded theory to generate a multilayered classification system, which
      culminated in a substantive theory on living with end-stage renal disease and
      hemodialysis. The qualitative database was revisited for the purpose of scale
      development and led to the Patient Perception of Hemodialysis Scale (PPHS). The
      quantitative study confirmed that the PPHS was psychometrically valid and
      reliable and supported the major premises of the substantive theory.

PMID- 19160741
TI  - Primer on systematic review and meta-analysis.
AB  - A systematic review uses an explicitly defined process to comprehensively
      identify all studies pertaining to a specific focused question, appraise the
      methods of the studies, summarize the results, identify reasons for different
      findings across studies, and cite limitations of current knowledge. Meta-analyses
      usually combine aggregate-level data reported in each primary study, which may
      provide a more precise estimate of the "true effect" than any individual study.
      However, the conclusions may be limited by between-trial heterogeneity,
      publication bias, or deficits in the conduct or reporting of individual primary
      studies.

PMID- 19160742
TI  - The role of health economics within clinical research.
AB  - The pressure for health care systems to provide more resource-intensive health
      care and newer, more costly therapies is significant, despite limited health care
      budgets. It is not surprising, then, that demonstration that a new therapy is
      effective is no longer sufficient to ensure that it can be used in practice
      within publicly funded health care systems. The impact of the therapy on health
      care costs is also important and considered by decision makers, who must decide
      whether scarce resources should be invested in providing a new therapy. The
      impact of a therapy on both clinical benefits and costs can be estimated
      simultaneously using economic evaluation, the strengths and limitations of which
      are discussed. When planning a clinical trial, important economic outcomes can
      often be collected alongside the clinical outcome data, enabling consideration of
      the impact of the therapy on overall resource use, thus enabling performance of
      an economic evaluation, if appropriate.

PMID- 19160743
TI  - Development and limitations of clinical practice guidelines.
AB  - Clinical practice guidelines are systematically developed statements to assist
      practitioners and patients reach appropriate health care decisions. If developed
      properly, clinical practice guidelines assimilate and translate an abundance of
      evidence published on a daily basis into practice recommendations and, in doing
      so, reduce the use of unnecessary or harmful interventions and facilitate the
      treatment of patients to achieve maximum benefit and minimum risk at an
      acceptable cost. Traditionally, clinical practice guidelines were consensus-based
      statements, often riddled with expert opinion. It is now recognized that clinical
      practice guidelines should be developed according to a transparent process
      involving principles of bias minimization and systematic evidence retrieval and
      review, with a focus on patient-relevant outcomes. The process for the
      development, implementation, and evaluation of clinical practice guidelines are
      reviewed in this chapter.

PMID- 19160744
TI  - Basics of health technology assessment.
AB  - This chapter begins with a brief introduction to health technology assessment
      (HTA). HTA is concerned with the systematic evaluation of the consequences of the
      adoption and use of new health technologies and improving the evidence on
      existing technologies. The objective of mainstream HTA is to support evidence
      based decision and policy making that encourage the uptake of efficient and
      effective health care technologies. This chapter provides a basic framework for
      conducting an HTA, as well as some fundamental concepts and challenges in
      assessing health technologies. A case study of the assessment of drug-eluting
      stents in Ontario is presented to illustrate the HTA process. Whether HTA is
      beneficial (supporting timely access to needed technologies) or detrimental
      depends on three critical issues: when the assessment is performed, how it is
      performed, and how the findings are used.

PMID- 19160745
TI  - Research ethics for clinical researchers.
AB  - This paper describes the history of the development of modern research ethics.
      The governance of research ethics varies according to geographical location.
      However, the guidelines used for research ethics review are very similar across a
      wide variety of jurisdictions. Protection of the privacy and confidentiality of
      research participants is of paramount importance. The process of informed consent
      and step-by-step practical guidelines are described. The issue of research in
      vulnerable populations is discussed and guidelines are provided. Practical advice
      is provided for researchers to guide their interactions with research ethics
      boards.

PMID- 19160746
TI  - Budgeting, funding, and managing clinical research projects.
AB  - Large, integrated multidisciplinary teams have become recognized as an efficient
      means by which to drive innovation and discovery in clinical research. This
      chapter describes how to budget and fund these large studies and effectively
      manage the large, often dispersed teams involved. Sources of funding are
      identified; budget development, justification, reporting, financial governance,
      and accountability are described; in addition to the creation and management of
      the multidisciplinary team that will implement the research plan.

PMID- 19160747
TI  - [Preparation of magnesia-zirconia based mimetic biomembrane stationary phase and
      its applications in evaluating drug-membrane interactions].
AB  - A novel mimetic biomembrane chromatographic stationary phase of magnesia-zirconia
      composite matrix was prepared based on the Lewis acid-base interaction between
      the phosphonate group of phosphatidylcholine residue and the Lewis acid sites of
      magnesia-zirconia composite. The infrared absorption spectrum and X-ray
      photoelectron spectrum of the stationary phase illustrated that the magnesia
      zirconia composite was successfully modified with phosphatidylcholine. The
      interactions between the membrane and the drugs were evaluated. It is observed
      that the log Kmbm values have good relationships with the log Papp, and the
      linear slope is 1.049, which is near unity. Moreover, on the basis of the
      thermodynamics derivation, the difference in standard free energies (delta (delta
      G0)) is introduced to describe the drug-membrane interaction. The results show
      that the log Kmbm, and delta (delta G0) value provide key information on the
      transport properties of the drugs. The establishment of this chromatographic
      model may be a new way for the evaluation of the drug-membrane interactions.

PMID- 19160748
TI  - [Identification of Mycobacterium species using reversed-phase high performance
      liquid chromatographic analysis of mycolic acid].
AB  - A method for the identification of Mycobacterium species using reversed-phase
      high performance liquid chromatography (RP-HPLC) was developed. The fingerprints
      library was constructed on the basis of RP-HPLC chromatograms of the mycolic
      acids derivatives from 49 Mycobacterium species cultures. Two inoculation loops
      of Mycobacterium, for fast growth with one week incubation or for slow growth
      with three weeks incubation, were saponified for 1 h and stocked at 4 degrees C.
      The mycolic acids from each culture of Mycobacterium species were acidified,
      extracted, derivatized, and analyzed by the RP-HPLC method. On the basis of the
      HPLC patterns of relative retention time and relative peak height, the
      identifications of Mycobacterium species were performed. This established method
      has a good precision of retention times with the relative standard deviations
      (RSDs) ranging from 0.13% to 1.07%. The mycolic acids fingerprints library of
      HPLC patterns was set up, including 49 species that were recorded in "Bergey's
      Manual of Systematic Bacteriology". Three patterns were observed from the
      chromatographic behaviors of mycolic acids derivatives, including single peak
      cluster, double peak-clusters, triple and multiple peak-clusters. Forty-one
      species were successfully identified according to the different relative
      retention times of the peaks and the relative peak heights. The established
      method can identify Mycobacterium species with rapidity and high reliability.

PMID- 19160749
TI  - [Analysis of the related substances in phosphorothioate antisense oligonucleotide
      FT19].
AB  - A method using anion exchange high performance liquid chromatography (AX-HPLC)
      and capillary gel electrophoresis (CGE) was established for the analysis of the
      related substances in phosphorothioate antisense oligonucleotide FT19 for quality
      control. The FT19 and its analogs of partial phosphodiester compounds (P=O) 1, as
      well as deletion sequences (n - 1) were analyzed. AX-HPLC with the DNA Pac PA-100
      column (4 mm x 250 mm) was used for the separation of phosphorothioate
      modifications. The size of the capillary column used in the CGE was 31 cm x 100
      microm with an effective length of 20 cm. It was found that full phosphorothioate
      and partial phosphodiester oligonucleotides of the same length were successfully
      separated, and the deletion sequences (n - 1) and the full-length sequence n were
      successfully separated in CGE. The results demonstrated that the related
      substances of phosphorothioate oligonucleotides can be well analyzed by AX-HPLC
      and CGE.

PMID- 19160751
TI  - [Determination of kinetic transformation of two geometrical isomers of the
      [Fe(PDT)3]2+ by high performance liquid chromatography].
AB  - The kinetic transformation of the two isomers of the [Fe(PDT)3]2+ (PDT: 3-(2
      pyridyl)-5,6-diphenyl-1,2,4-triazine) was studied by high performance liquid
      chromatography. The transformation between two isomers was proved to be treated
      kinetically as the first-order reaction. At different reaction temperatures, the
      linear regression equations between x(e)ln[(x(e) - x(0))/(x(e) - x)] and t(min)
      were as follows: x(e)ln[(x(e) - x(0))/(x(e) - x)] = 0.082t + 0.729 (r2 = 0.9911,
      T = 45 degrees C), x(e)ln[(x(e) - x(0))/(x(e) - x)] = 0.049t + 0.598 (r2 =
      0.9987, T = 40 degrees C), x(e)ln[(x(e) - x(0))/(x(e) - x)] = 0.022t + 0.586 (r2
      = 0.9987, T = 35 degrees C), x(e)ln[(x(e) - x(0))/(x(e) - x)] = 0.012t + 0.591
      (r2 = 0.9988, T = 30 degrees C). The activation enthalpy (delta H), activation
      entropy (delta S), and activation energy (delta Ea) characterizing the kinetic
      transformation were as follows: delta H = 103.84 kJ x mol(-1), delta S = 271.93 J
      x mol(-1) x K(-1), delta Ea = 86.74 kJ x mol(-1) (fac-isomer --> mer-isomer);
      delta H = 106.47 kJ x mol(-1), delta S = 257.65 J x mol(-1) x K(-1), delta Ea =
      94.43 kJ x mol(-1) (mer-isomer --> fac-isomer).

PMID- 19160750
TI  - Simultaneous determination of olmesartan medoxomil and irbesartan and
      hydrochlorothiazide in pharmaceutical formulations and human serum using high
      performance liquid chromatography.
AB  - A simple, selective, sensitive, precise, simultaneous high performance liquid
      chromatographic analysis of serum samples and commercial tablet formulation
      containing hydrochlorothiazide, olmesartan medoxomil and irbesartan are reported.
      Good chromatographic separation was achieved using a micro-Bondapak, C18 column
      (15 cm x 4.6 mm, 5 microm), and a mobile phase consisting of acetonitrile-0.2%
      acetic acid aqueous solution (50:50, v/v) at a flow rate of 1.0 mL/min. The
      ultraviolet detector was set at a wavelength of 260 nm. Hydrochlorothiazide,
      olmesartan medoxomil, and irbesartan were eluted at 1.2, 3.8, and 4.4 min,
      respectively. No extraneous materials were found to interfere. The method uses
      protein precipitation with acetonitrile for the preparation of serum sample. The
      linear ranges for hydrochlorothiazide, olmesartan medoxomil, and irbesartan were
      6.25-18.75, 20-60, and 75-225 ng/mL, respectively. The recoveries of
      hydrochlorothiazide, olmesartan medoxomil, and irbesartan in spiked samples were
      all greater than 98%, and their relative standard deviations were less than 2.0%.
      The limits of detection were 1, 2, and 2 ng/mL for hydrochlorothiazide,
      olmesartan medoxomil, and irbesartan, respectively, and the limits of
      quantification were 3 ng/mL, which allow their determination at the expected
      serum concentration levels.

PMID- 19160752
TI  - [Determination of 22 components in hair dyes by high performance liquid
      chromatography].
AB  - A high performance liquid chromatographic (HPLC) method was developed for the
      determination of 22 components in hair dyes. The target analytes were separated
      on an amide bonded C16 silica column (250 mm x 4.6 mm, 5 microm), employing
      acetonitrile-0.025 mol/L phosphate buffer (pH 6.0) containing 0.1% 1
      heptanesulfonic acid sodium salt as the mobile phase and detected by a photodiode
      array detector (DAD) with the detection wavelengths of 260 nm and 280 nm. The
      flow rate was 1. 0 mL/min and the column temperature was 25 degrees C. The linear
      range was from 10 mg/L to 500 mg/L with good relationship. The relative standard
      deviations were less than 10% (except toluene-2,5-diamine sulfate, 2
      methylresorcinol, N,N-diethyltoluene-2,5-diamine HCl at low concentrations) and
      the recoveries were from 77.6% to 122.8%. The method is simple, rapid and
      accurate, and is suitable for the analysis of various hair dyes.

PMID- 19160753
TI  - [Resolution of thyroxine hormone enantiomers by precolumn derivatization with a
      fluorescent chiral reagent using reversed-phase high performance liquid
      chromatography].
AB  - A highly fluorescent chiral tagging reagent, R(-)-4-(N,N-dimethylaminosulfonyl)-7
      (3-isothiocy-anatopyrrolidino)-2,1,3-benzoxadiazole (R(-)-DBD-PyNCS), was
      employed for the enantiomer separation of thyroxine hormone, D,L-3,5,3',5'
      tetraiodothyronine (T4) and L-3,5,3'-triiodothyronine (T3). The reaction of R(-)
      DBD-PyNCS with the thyroxine enantiomers was carried out at 40 degrees C for 20
      min under a basic medium surrounding to yield the corresponding pair of
      diastereomers. No racemization occurs during the tagging reaction under the
      optimized conditions. Various experimental parameters for the derivatization
      reaction including the concentration of tagging reagent, reaction temperature and
      reaction time have been studied in order to get the highest yield of T4/T3
      derivatives. The structures of T4/T3 derivatives were identified based on high
      performance liquid chromatography-mass spectrometry (HPLC-MS) measurement in
      negative mode. The efficient separation of derivatives have been achieved by
      isocratic elution with a water-acetonitrile mobile phase containing 1% acetic
      acid in a reversed-phase column utilizing a conventional fluorescence detector.
      The calibration curves of L-T3, D,L-T4 were linear over the concentration ranges
      of 0.0067-0.22 microg/microL and 0.016-0.30 microg/microL, respectively. The
      limits of detection (S/N = 3) for L-T3 and D,L-T4 were 0.85 microg/mL and 0.02
      microg/mL, respectively. The proposed method has been successfully applied to the
      determination of T3 and T4 in clinical pharmaceutics.

PMID- 19160754
TI  - [Determination of benomyl, carbendazim and thiabendazole in apple juice
      concentrate using solid-phase extraction coupled with ion exchange
      chromatography].
AB  - A method was developed for the determination of benomyl, carbendazim and
      thiabendazole in apple juice concentrate by solid-phase extraction coupled with
      ion exchange chromatography (IEC). The sample was diluted with water, and then
      benomyl was degradated completely to carbendazim at 80 degrees C, and purified by
      an SCX solid-phase extraction column. Liquid chromatographic analysis was
      performed on the instrument of Agilent 1200 series equipped with a diode-array
      detector and autosampler. The column was LC-SCX (25 cm x 4.6 mm, 5 microm). The
      mobile phase was 0.1 mol/L KH2PO4 (pH 2.5)-acetonitrile (70:30, v/v) with a flow
      rate of 1.0 mL/min. The presented method showed good linear relationship with
      good precision and accuracy at the range of 0.02 - 2.0 mg/L for carbendazim and
      thiabendazole. The detection limits were 0. 004 mg/kg for carbendazim and
      thiabendazole. The method was characterized with acceptable sensitivity to meet
      the requirements for monitoring these pesticides in apple juice concentrate.

PMID- 19160755
TI  - [Determination of 92 pesticide residues in tea by gas chromatography with solid
      phase extraction].
AB  - A multiresidue analytical method was developed for the determination of ninety
      two pesticides in tea using solid-phase extraction (SPE) and gas chromatographic
      determination. Tea samples were extracted with acetonitrile, organophosphorus
      pesticides were clean-up by an Envi-Carb SPE cartridge, eluted with 10 mL
      acetonitrile-toluene (3:1, v/v) and determined by gas chromatography-flame
      photometric detection (GC-FPD); organochlorine pesticides and pyrethroids
      pesticides were cleaned-up by Envi-Carb + NH2 SPE cartridges, eluted with 5 mL
      acetonitrile-toluene (3:1, v/v) and determined by gas chromatography-electron
      capture detection (GC-ECD). The recoveries of those pesticides were ranged from
      80.3% to 117.1% by fortification test with the relative standard deviations being
      from 1.5% to 9.8%. The limits of detection were 0.0025 - 0.10 mg/kg. The proposed
      method is characterized by simplicity, higher sensitivity and accuracy.

PMID- 19160756
TI  - [A rapid multi-residual analysis for organophosphorus pesticides in the products
      of animal origin using gas chromatography coupled with accelerated solvent
      extraction and gel permeation chromatographic purification].
AB  - A rapid method has been developed to determine the multi-residues of 36
      organophosphorus pesticides in the products of animal origin using capillary gas
      chromatography with flame photometric detector (GC-FPD (P)). The organophosphorus
      pesticides were extracted with acetonitrile by accelerated solvent extraction,
      and cleaned up by auto gel permeation chromatography and primary secondary amine
      (PSA) packing material. The collected solution was analyzed by the GC-FPD (P) and
      quantified by internal standard method. The 36 organophosphorus pesticides were
      separated efficiently from impurity in high sensitivity and reproducibility by GC
      FPD (P). The limits of detection (LODs) ranged from 0.0012 mg/kg (phorate) to
      0.014 mg/kg (pyraclofos), and the limits of quantitation (LOQs) ranged from 0.004
      mg/kg (phorate) to 0.047 mg/kg (pyraclofos). The recoveries ranged from 58.2% to
      106.3% in blank samples spiked with 0.05, 0.1 and 0.2 mg/kg of 36
      organophosphorus pesticides. The LODs, LOQs and the recoveries of the method all
      satisfy the requirement of pesticide residue analysis.

PMID- 19160757
TI  - [Determination of 28 organochlorine and synthetic pyrethroid pesticides in greasy
      wool using accelerated solvent extraction technique and gas chromatography].
AB  - A method for the simultaneous determination of 28 organochlorine and synthetic
      pyrethroid pesticides in greasy wool was developed by accelerated solvent
      extraction (ASE) coupled with gas chromatography-electron capture detection (GC
      ECD). The organochlorine and synthetic pyrethroid pesticides in greasy wool were
      extracted with acetonitrile saturated with n-hexane at 80 degrees C, 10.34 MPa by
      ASE. The extract was pretreated by a series of procedures such as freezing-lipid
      filtration, concentration and purification by solid-phase extraction prior to the
      determination with GC-ECD. The linear ranges were 0.005-1.0 mg/L for 16
      organochlorines, 0.02-4.0 mg/L for flumethrin and 0.01-2.0 mg/L for the others.
      There were good linear relationships between the peak area and concentration in
      the linear ranges. The average recoveries of 28 organochlorine and synthetic
      pyrethroid pesticides were 67.2%-107.7%, and the relative standard deviations
      were 2.6%-29.0%. The method is simple, sensitive and suitable for preliminary
      screening of organochlorine and synthetic pyrethroid pesticides in greasy wool.

PMID- 19160758
TI  - [Analysis of phenolic compounds in aqueous samples by gas chromatography coupled
      with headspace solid-phase microextraction using poly (phthalazine ether sulfone
      ketone) coated fiber].
AB  - The direct trace analysis of phenolic compounds in aqueous samples was performed
      by headspace solid-phase microextraction/gas chromatography (HS-SPME/GC). A
      laboratory made poly (phthalazine ether sulfone ketone) (PPESK, 30 microm) coated
      fiber was used to extract the phenols from aqueous samples. The parameters
      affecting the extraction efficiency, such as extraction temperature and time, pH
      value, and salt concentration, were optimized. The low pH value and high salt
      concentration can increase the extraction efficiency of phenols. The limits of
      detection (LODs) were from 0.003 to 0.041 microg/L, which were within the range
      of EPA Method 604. The relative standard deviations (RSDs) were less than 16%.
      Compared with commercial polyacrylate (PA) fiber (85 microm), the PPESK fiber
      shows high affinity toward phenolic compounds, and therefore, high absolute
      recoveries. The phenols were detected with the recoveries of 100.5%-111.8% for a
      tap water sample and 94.8%-117.3% for a seawater sample at the spiked level of 20
      microg/L.

PMID- 19160759
TI  - [Determination of hydroxyproline in collagenous proteins by high performance
      liquid chromatography-mass spectrometry].
AB  - A simple, rapid and accurate method for the determination of hydroxyproline in
      collagenous proteins by high performance liquid chromatography-electrospray mass
      spectrometry (HPLC-ESI/MS) was developed. After hydrolysis of collagenous
      proteins with hydrochloric acid, the hydroxyproline was separated on a Spherigel
      C8 column using acetonitrile-0.05% trifluoroacetic acid aqueous solution (5:95,
      v/v) at a flow rate of 1.0 mL/min. Theanine was used as the internal standard for
      the quantification. Hydroxyproline was identified and quantified by electrospray
      ionization mass spectrometry (ESI-MS), which was operated in positive ion mode
      while the m/z 132 and m/z 175 ions were recorded in the selective ionization
      monitoring (SIM) mode. The peak area ratio of hydroxyproline to theanine versus
      the hydroxyproline concentration was linear over a concentration range of 11.7
      117 mg/L for hydroxyproline. The correlation coefficient was 0.999 3. The
      reproducibility and average recovery of the method were 1.87% and 98.85%
      respectively. The method has the advantages of easy operation, without
      derivatization, less analysis time, good precision and accuracy.

PMID- 19160760
TI  - [Simultaneous determination of five effective components in Qingrejiedu oral
      liquid using high performance liquid chromatography-mass spectrometry].
AB  - A high performance liquid chromatography-electrospray ionization mass
      spectrometry (HPLC-ESI/MS) method for the simultaneous determination of five
      effective components in Qingrejiedu oral liquid was developed. The HPLC
      separation was performed on a Zorbax SB C18 column (250 mm x 3.0 mm, 5 microm)
      using 0.4 mmol/L sodium acetate solution containing 0.2% formic acid (A) and
      acetonitrile (B) as the mobile phase with gradient elution (0 min, 10% B; 0 --> 6
      min, 10% B --> 30% B; 6 --> 15 min, 30% B --> 39% B; 15 --> 16 min, 39% B --> 80%
      B) at a flow rate of 0.35 mL/min. The analytes were detected by ESI(+)-MS under
      selected ion monitoring mode (0 --> 9.7 min, m/z 377; 9.7 --> 12 min, m/z 411; 12
      --> 14.7 min, m/z 447; 14.7 --> 18 min, m/z 557; 18 --> 25 min, m/z 263). The
      linear ranges were 0.050-50 mg/L, 0.020-20 mg/L, 0.005-30 mg/L, 0.010-15 mg/L and
      0.010-10 mg/L with detection limits of 0.010, 0.005, 0.001, 0.002 and 0.003 mg/L
      for chlorogenic acid, geniposide, baicalin, forsythin and indirubin,
      respectively. The average recoveries ranged from 97.0% to 101.7%. The relative
      standard deviations were less than 2.2%. This method is rapid, accurate, and
      suitable for the quality control of the five effective components in Qingrejiedu
      oral liquid.

PMID- 19160761
TI  - [Fast separation and identification of nine carcinogenic dyes in textiles using
      liquid chromatography-electrospray tandem mass spectrometry].
AB  - A qualitative method of the identification of nine carcinogenic dyes prohibited
      in textiles was developed using high performance liquid chromatography-tandem
      mass spectrometry interfaced with electro-spray ionization (HPLC-ESI-MS/MS) in
      the selective reaction monitoring (SRM) mode. The dyes were extracted from
      textiles composed of natural or chemical fibers by methanol under
      ultrasounication, and then eluted with gradient by acetonitrile and 5 mmol/L
      ammonium acetate from an RP-C18 column with two segments in effluents. The first
      effluents accommodated Acid Red 26, Direct Blue 6, Direct Black 38 and Direct Red
      28 with negative ionization mode, while the second accommodated Basic Red 9,
      Basic Violet 14, Disperse Blue 1, Disperse Orange 11 and Disperse Yellow 3 with
      positive ionization mode. Thus the investigated compounds could be identified
      simultaneously with single-run analysis no matter which type of the fibre the
      sample was and no matter which category of the dye the analyte was. The
      established method was successfully applied to identify the carcinogenic dyes in
      textile samples through comparing the chromatographic retention time and the
      relative abundance of characteristic product ions with the standards.

PMID- 19160762
TI  - [Determination of 14 pesticide residues in sulfur-containing vegetables by gas
      chromatography-negative chemical ionization mass spectrometry].
AB  - A gas chromatography-negative chemical ionization mass spectrometric (GC-NCI/ MS)
      method has been developed for analyzing 14 pesticide residues in sulfur
      containing vegetables (scallion, garlic, garlic bolt, leek, etc.). The samples
      were first heated in a microwave oven to eliminate most of the sulfur-containing
      interfering impurities and then extracted with acetonitrile. The extracts were
      further cleaned-up by gel permeation chromatography (GPC) and a primary-secondary
      amine (PSA) cartridge. The target analytes were determined using GC-NCI/MS in the
      selected ion monitoring (SIM) mode. The recoveries of all the pesticides (at
      spiked level of 50 microg/kg) were from 49.2% to 113.1% with the relative
      standard deviations between 1.42% and 8.70%. The detection limits (S/N = 3) were
      in the range of 0.5-10.0 microg/kg. The method is selective without interference
      and suitable for the determination and confirmation of pesticides in the sulfur
      containing vegetables.

PMID- 19160763
TI  - [Pyrolysis-gas chromatographic fingerprints with hierarchical cluster analysis
      for Dendrobium candidum Wall. ex Lindl].
AB  - The pyrogram fingerprints of Dendrobium candidum Wall. ex Lindl. from different
      regions were studied by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS)
      and compared with hierarchical cluster analysis. The effect of pyrolysis
      temperature on the fingerprint was examined by evolved gas analysis, and then 450
      degrees C was selected as the optimized pyrolysis temperature. An amount of 0.4
      mg of raw drug powder was pyrolysed in a vertical microfurnace pyrolyzer, and the
      products were directly introduced into a gas chromatograph equipped with a flame
      ionization detector (FID) and a fused-silica capillary column (30 m x 0.25 mm x
      0.25 microm). The pyrogram fingerprints of 10 samples from different regions
      showed a high similarity and a good reproducibility with the relative standard
      deviations (RSDs) of the retention times less than 0.33% and the RSDs of the
      relative peak areas less than 4.8%. Therefore, each sample was characterized by
      the peak area of 31 peaks in each pyrogram and these peaks were employed for
      hierarchical cluster analysis. Furthermore, the discrimination of the sample from
      different regions was achieved by hierarchical cluster analysis via recognizing
      the 10 x 31 data matrix. Thus, the results proved it is a simple, rapid and
      accurate method suitable for the quality control of the traditional Chinese
      medicines.

PMID- 19160764
TI  - [Determination of environmental estrogens in pharmacy wastewater using solid
      phase extraction-gas chromatography/mass spectrometry with derivatization].
AB  - A method for the determination of estrone (E1), estradiol (E2), ethinylestradiol
      (EE2) and estriol (E3) in pharmacy wastewater was developed using solid-phase
      extraction-gas chromatography/mass spectrometry (SPE-GC/MS) with derivatization.
      The sample was extracted by an SPE column, derivatized by bis (trimethylsilyl)
      trifluoroacetamide (BSTFA), and analyzed by GC/MS. The detection limits were 1.8
      4.7 ng/L, and the relative standard deviations were 2.3%-9.1% (n = 8). The
      recoveries of above four environmental estrogen compounds were (94.0 +/- 2.9)% to
      (101 +/- 3.8)%. The method can be applied in the determination of the estrogenic
      compounds in wastewater samples successfully. The concentrations of EE2 and E1 in
      wastewater were 396.6 ng/L and 39.9 ng/L, respectively, and the removal rates of
      EE2 and E1 were 35%-40% after traditional biological treatment. The results
      demonstrated that the removal efficiency was not satisfactory and the traditional
      treatment process of wastewater containing estrogen compounds from
      pharmaceuticals factory should be improved.

PMID- 19160765
TI  - [Urine profiling by capillary electrophoresis with online stacking of moving
      reaction boundary].
AB  - Rapid and sensitive profiling of urine holds evident significance for the
      discovery of new biomarkers and clinical diagnosis. In this study, a simple,
      rapid and sensitive moving reaction boundary (MRB)-induced stacking technique is
      described for the analysis of urine profiling by capillary zone electrophoresis
      (CZE). The MRB was formed with acidic Gly-HCl as the sample buffer and alkaline
      Gly-NaOH as the running buffer. The optimum conditions of stacking and separation
      were: 25 mmol/L Gly-HCl (pH 2.5) as the sample buffer and 50 mmol/L Gly-NaOH (pH
      12.3) as the running buffer, 15 kV of applied voltage, 4.82 kPa (0.7 psi) x 20 s
      of pressure injection, 60.2 cm x 75 microm i.d. (50 cm effective length) of
      capillary, 214 nm of detection wavelength, 24 degrees C of separation
      temperature. Under the optimum conditions, the MRB can significantly improve the
      sensitivity of urine profiling. More than 80 stacking peaks have been observed
      and more than 10 fold sensitivity enhancement was achieved in contrast with the
      conventional CZE, which with only ten observable peaks and poor sensitivity. The
      results indicate that the MRB-induced stacking is a useful and potential tool for
      urine profiling. Furthermore, the present method is easy to perform, and the
      preparation of sample is quite simple.

PMID- 19160766
TI  - [Analyse of sugars in beer and wort using high performance anion-exchange
      chromatography coupled with pulsed amperometric detection].
AB  - The method of the simultaneous and direct analysis of eleven sugars, including
      monosaccharides, disaccharides and oligosaccharides, was established using high
      performance anion-exchange chromatography (HPAEC) coupled with pulsed
      amperometric detection (PAD) using an Au working electrode and a pH-Ag/AgCl
      reference electrode. The separation was accomplished on a CarboPac PA-100 column
      by using gradient elution consisting of water, 0.25 mol/L NaOH and 1 mol/L NaAc
      as mobile phase at a flow rate of 0.25 mL/min. Under these conditions, glucose,
      fructose, sucrose, maltose, isomaltose, maltotriose, isomaltotriose,
      maltotetraose, maltopentaose, maltohexaose and maltoheptaose were separated in 40
      min. Then sugars were detected directly with PAD method without any
      derivatization reaction, and there was no need to employ complicated pretreatment
      procedures to the samples before analysis. The detection limits (S/N = 3) for the
      sugars were 13-88 pg. The proposed method was applied for the determination of
      the 11 sugars in beer and wort samples satisfactorily, with the spiked recoveries
      of most sugars ranging from 81% to 107%. In addition, some potential transition
      mechanism of the sugars during the brewage procedure can be educed from the
      comparison of sugar contents between beer and wort.

PMID- 19160767
TI  - [Chiral separation of racemic epoxiconazole on cellulose tris(3,5
      dimethylphenylcarbamate) chiral stationary phase using high performance liquid
      chromatography].
AB  - The two pairs of enantiomers of epoxiconazole were resolved using normal phase,
      reversed-phase and polar organic solvent high performance liquid chromatography
      on cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) chiral stationary phase,
      separately. The effects of different mobile phase compositions on the retention
      factor, separation factor and resolution in the chiral separation of
      epoxiconazole were investigated. It can be baseline separated on a Chiralcel OD-H
      column packed with CDMPC chiral stationary phase when methanol-water (80: 20,
      v/v) was used as the mobile phase, the resolutions of the two pairs of
      enantiomers were 1.64 and 6.50, respectively.

PMID- 19160768
TI  - [Determination of 1-deoxynojirimycin in Morus alba L. leaves using reversed-phase
      high performance liquid chromatography fluorescence detection with pre-column
      derivatization].
AB  - A rapid, reliable and suitable method for the determination of 1-deoxynojirimycin
      (DNJ) in Morus alba L. leaves has been developed. The DNJ in 100 mg dried leaves
      was extracted twice with 10 mL aqueous 0.05 mol/L HCl, then derivatized by 6
      aminoquinoiyi-N-hydroxysuccinimidyl carbamate (AQC) in K3BO3 buffer (pH 8.5), and
      analyzed using a high performance liquid chromatograph equipped with a
      fluorescence detector. The analyte was eluted with a mobile phase of 0.02 mol/L
      potassium dihydrogen phosphate buffer-acetonitrile (85: 15, v/v) at the rate of
      1.0 mL/min. The derivatized DNJ was well dissolved from the hydrolysis products
      of AQC. The linearity ranged from 0.5 to 25 mg/L, and the detection limit was
      0.02 mg/L (S/N = 3). The content of DNJ in Morus alba L. leaves was 0.12%, the
      recovery was 96.1%-98.6%.

PMID- 19160769
TI  - [Simultaneous determination of atractylenolide III, atractylenolide I and
      atractylon in Artactylodis macrocephala using microbore liquid chromatography].
AB  - A microbore liquid chromatography (microbore LC) has been developed for the
      simultaneous determination of atractylenolide III, atractylenolide I and
      atractylon in Artactylodis macrocephala. In the method, a Microsil C18 column
      (150 mm x 1.0 mm) was used with the mobile phase containing methanol-acetonitrile
      water for gradient elution, the flow rate was 50 microL/min, and the detection
      wavelength was set at 220 nm. Under the optimized separation conditions, every
      component was separated thoroughly. The relationships between the concentrations
      and the peak areas of the three components were all linear. The recoveries were
      96.86% for atractylenolide III, 97.13% for atractylenolide I and 98.06% for
      atractylon, the relative standard deviations (RSD) were 1.63%, 1.31% and 0.39%,
      respectively. The method is simple, convenient, and can be used for the quality
      control of Artactylodis macrocephala.

PMID- 19160770
TI  - [Simultaneous determination of adapalene, 2-phenoxyethanol and methyl-4
      hydroxybenzoate in adapalene gels using high performance liquid chromatography].
AB  - A reversed-phase high performance liquid chromatographic (RP-HPLC) method was
      developed for the simultaneous determination of the contents of adapalene and the
      preservatives (2-phenoxyethanol and methyl-4-hydroxybenzoate) in adapalene gels.
      The chromatographic analysis was carried out on a Tigerkin C18 column (150 mm x
      4.6 mm, 5 microm). The mobile phase was 0.02 mol/L ammonium acetate buffer (pH
      3.0) and tetrahydrofuran-acetonitrile with gradient elution, and the detection
      wavelength was set at 270 nm. The calibration curves were linear over the ranges
      of 10-100 mg/L (r = 0.9999), 4-40 mg/L (r = 0.9999) and 4-40 mg/L (r = 0. 9999)
      for 2-phenoxyethanol, methyl-4-hydroxybenzoate and adapalene, respectively. The
      average recoveries of the three substances were within 98.0%-98.6%. The method is
      simple, reliable and suitable for the simultaneous determination of adapalene, 2
      phenoxyethanol and methyl-4-hydroxybenzoate in adapalene gels.

PMID- 19160771
TI  - [Enantiomeric separation of liarozole on amylose chiral stationary phase].
AB  - A high performance liquid chromatographic method was established for the
      enantiomeric separation of liarozole. Baseline chiral separation of liarozole was
      achieved under normal-phase chromatographic mode by the Chiralpak AD-H chiral
      stationary phase. The influences of the concentration and kind of organic
      solvent, the proportion of acid and base, column temperature and flow rate on the
      enantiomeric separation were studied. The optimized chromatographic conditions
      were hexane-ethanol (containing 0.3% diethylamine and 0.1% glacial acetic acid)
      (80:20, v/v) as the mobile phase with a flow rate of 0.6 mL/min and detection at
      the wavelength of 254 nm. The column temperature was set at 20 degrees C. The
      resolution of 3.4 for liarozole was achieved under the above chromatographic
      conditions. The method is simple, rapid and with good reproducibility.

PMID- 19160772
TI  - [Determination of decabromodiphenyl ethane using high performance liquid
      chromatography].
AB  - A method was developed for the quantitative determination of decabromodiphenyl
      ethane (DBDPE) using high performance liquid chromatography (HPLC). The sample
      was separated on a Zorbax C18 column (5 microm, 150 mm x 4.6 mm) at the
      temperature of 40 degrees C with the elution of methanol-tetrahydrofuran (70:30,
      v/v) as mobile phase at a flow rate of 0.8 mL/min. The detection wavelength was
      230 nm. The assay exhibited a good linearity in decabromodiphenyl ethane
      concentration range from 0.001 to 0.100 g/L with a correlation coefficient of
      0.9991. The limit of detection was 0.2 mg/L. The recovery was more than 96% (n =
      4), and the relative standard deviation was 4.0% (n = 6). This method can be
      applied in the industrialized production for replacing the thermal analysis.

PMID- 19160773
TI  - [Advance on study in anti-atherosclerosis mechanism of berberine].
AB  - Coptis chinensis is a traditional Chinese herb that has the effect of clearing
      heat and drying dampness, purging fire to eliminate toxin. Berberine is the main
      alkaloid of C. chinensis, and researches showed recently, berberine had the
      effect of anti-atherosclerosis. This paper has reviewed the mechanism of
      berberine in anti-atherosclerosis from anti-inflammation, regulating lipid,
      decompression, reducing blood sugar, and inhibiting vascular smooth muscle cell
      proliferation.

PMID- 19160774
TI  - [Research progress on effect of coumarins compounds in anti-tumor].
AB  - Coumarins are a group of important natural compounds, and have been found to have
      multi-biological activities such as anti-HIV, anti-tumor, anti-hypertension, anti
      arrhythmia, anti-osteoporosis, assuaging pain, preventing asthma and antisepsis.
      One of which is its anti-tumor effect and that is a research focus on. Therefore,
      we believe that it is necessaryto carry out further studies on the effect of
      coumarins compounds in anti-tumor. Investigation should emphasize on improving
      techniques for extraction and separation, searching the effective precursory
      compound, and synthesizing and screening out courmarin derivatives with high
      activity and low toxicity. Here the recent research progress in anti-tumor effect
      of coumarins compounds is reviewed.

PMID- 19160775
TI  - [Resources of Lycium species and related research progress].
AB  - Solanaceae Lycium speices are deciduous shrubs. In ancient Chinese medicine
      works, Lycium plants are described to work well in nourshing liver and kidney,
      enhancing eyesight, enriching blood, invigorating sex, reducing rheumatism and so
      on. More of their functions such as immunity improvement, anti-oxydation, anti
      aging, anti-cancer, growth stumulation, hemopoiesis enhancing, incretion
      regulating, blood sugar reducing, bearing improvement and many other new
      functions are conformed in modern clinic researches. Lycium is also widely used
      in brewing, beverage and many other products. The world Lycium-related researches
      are mostly on Lycium species genesis and evolution, sexual evolution, active
      ingredient separation and pharmacological effects. The future research direction
      is indicated in this article, molecular evolution and systematics rather than
      traditional taxonomy will do better in explanation of present global distribution
      of Lycium species; comparative genomics research on Lycium will be a whole new
      way to deep gene resources exploration; relationship of genetic diversity and
      active ingredient variation on L. barbarum and L. chinense will lay theory basis
      for new germplasm development, breeding, cultivation and production
      regionalization.

PMID- 19160776
TI  - [Progressive studies of paeoniflorin].
AB  - Paeoniflorin is one of the bioactive components of Paeonia lactiflora, a
      traditional Chinese herbal medicine. It is the main monoterpene glucoside
      isolated from the P. lactiflora in 1963. Since then, researchers have found that
      paeoniflorin has multifold pharmacological effects. In this review, based on the
      recent available papers published in PubMed and National Knowledge Infrastructure
      Data Base, we present the major current approaches in understanding the detection
      methodology, pharmacokinetics and pharmacology, and toxicology of paeoniflorin.

PMID- 19160777
TI  - [Comparative analysis of character on germplasm resources of Rehmannia
      glutinosa].
AB  - OBJECTIVE: To compare difference in character between wild germplasm and cultivar
      of Rehmannia glutinosa Libosch. METHOD: Field test and statistical analysis were
      applied. RESULT: The results showed that the plant height and leave weight of
      individual plant in cultivar were decreased significantly comparing to wild
      germplasm, and the output was increased significantly. The leave length was
      reduced. The leave width, the catalpol content in leave and polysaccharides and
      reducing sugar content in cultivar was increased not significantly. Whereas the
      catalpol content and the water extract content in cultivar were equal to wild
      germplasm. CONCLUSION: The plant height and leave weight of individual plant of
      R. glutinosa was decreased significantly in cultivar, but the active compounds
      content not changed obviously.

PMID- 19160778
TI  - [ISSR-PCR analysis in different species and populations of Rhizoma Curcumae].
AB  - OBJECTIVE: To study the genetic diversity and genetic relationship in different
      species and populations of Curcuma by ISSR-PCR marker technique. METHOD: Eighty
      populations and 37 samples of Curcuma including C. phaeocaulis, C. kwangsiensis
      and C. wenyujin were studied by ISSR-PCR markers. The systematic diagram of
      Similar coefficient and genetic distance were set up by POPGEN32 software and
      clustered by UPGMA method. RESULT: A total of 65 loci were scored by 5 primers,
      among which 34 were polymorphic loci. The percentage of polymorphic loci was
      52.3%. Genetic similarity coefficient changed from 0.6864 to 0.9997. Nei's gene
      diversity index (H), and Shannon information index (I) were 0.1521 and 0.2338.
      The inner genetic diversity of Curcuma species was lower than the outer.
      CONCLUSION: The genetic variation of different populations Curcuma was big. The
      inherited differentiation of inner populations was low. Different populations of
      Curcuma were related to character of species and geological distribution.

PMID- 19160779
TI  - [Statistical analysis of residues of heavy metals in Chinese crude drugs].
AB  - OBJECTIVE: To analyze the residues of heavy metals in Chinese crude drugs.
      METHOD: The SPSS 13.0 software was used to analyze the data of Cu, Pb, As, Cd, Hg
      collected in literatures. And, Green Trade Standards of Importing & Exporting
      Medicinal Plants & Preparations was used as the standard to evaluate the
      pollution condition of Cu, Pb, As, Cd, Hg in Chinese crude drugs. RESULT: Chinese
      crude drugs were contaminated by heavy metals in different levels. The content of
      Cu, Pb, As, Cd, Hg exceeded the limit of the standard and the percentage was
      21.0%, 12.0%, 9.7%, 28.5%, 6.9%, respectively; the phenomena of two, three and
      four metals exceeding limited standard simultaneity in a drug were also found and
      the percentage was 4.6%, 1.5%, 0.7%, respectively; the content of heavy metals in
      Radix Platycodi, Radix Asari and Rhizoma Coptidis was higher among the thirty-six
      Chinese crude drugs; All of the content of five heavy metals in Barbary Fructus
      Lycii Rhizoma Anemones Raddeanae, Radix Panacis Quiquefolii and Fructus Aurantii
      were below the limit; The pollution levels of heavy metals in different locality
      were different; The content of Cu, Pb in cultivated Chinese crude drugs was
      higher than that in wild Chinese crude drugs, while the content of As in wild
      Chinese crude drugs was higher than that in cultivated Chinese crude drugs.
      CONCLUSION: The pollution levels of heavy metals in Chinese crude drugs were
      detailed reported in this paper. And it provided ways for the further study of
      heavy metals in Chinese crude drugs.

PMID- 19160780
TI  - [Release kinetics of oridonin self-microemulsifying drug delivery system in
      vitro].
AB  - OBJECTIVE: To investigate the release characteristics and mechanism of oridnonin
      self-microemulsifying drug delivery system (SMEDDS) in vitro. METHOD: The
      concentration of oridonin was determined by HPLC. In vitro release studies were
      conducted by reverse dialysis technique. The effects of release medium, agitation
      rate and preparations on the oridonin release were studied. The similarity factor
      (f2) was applied to the release profile comparisons. Model fitting was used to
      determine the kinetics and mechanism. RESULT: The release media and agitation
      rate from 50-100 r x min(-1) had no distinctive effect on the oridonin release
      kinetics, which the similarity factors were greater than 50. The oridonin release
      profiles for oridonin SMEDDS and oridonin ethanol solution were similar. 65% of
      oridonin were released in 30 min for oridonin SMEDDS in pH 7.8 PBS. Oridonin
      SMEDDS fit the Hixson-Crowell model best. CONCLUSION: The release data from
      oridonin SMEDDS showed it release fast. The deduced release mechanism is that the
      surface and particle sizes of self-microemulsion in water solution are changing
      during the process of release and the drug penetration through membrane is a
      passive diffusion process.

PMID- 19160781
TI  - [Comparisons between NIR and HPLC fingerprint on quality stability of Shudihuang
      decoction pieces].
AB  - OBJECTIVE: To establish a new method for evaluating quality stability of
      Shudihuang decoction pieces with near-infrared spectrum. METHOD: Clustering
      analysis was used to distinguish different Shudihuang samples. And comparisons
      between NIR and HPLC fringerprint. RESULT: Results of clustering reflected the
      similar degree among these samples. Compared with HPLC fingerprint, NIR
      analytical process fast and convenient with exact results. CONCLUSION: NIR is a
      feasible and effective approach to examine the quality stability of Shudihuang
      decoction pieces with unique virtues.

PMID- 19160782
TI  - [AMWFA method applied to research on changes of essential components and
      extractive ratioes of herbal pair Cinnamomum cassia and Poria cocos].
AB  - Gas chromatography/mass spectrometry, chemometric resolution method-Alternative
      movingwindow factor analysis that were proposed recently and the Kovats retention
      index were used to analyze the essential components of herbal pair Cinnamomum
      cassia Presl and Poria cocos (CCP-PC) and compare them with those of single
      herbal Cinnamomum cassia Presl (CCP). 46 and 42 essential components in essential
      oil of CCP and CCP-PC have been identified individually. Results shows that the
      number of essential components of CCP and CCP-PC were almost the same, but
      extractive ratioes of them have changed significantly, some of them were
      increased obviously, most of them were declined notably instead and even several
      ingredients of CCP-PC were disappeared due to CCP PC's interaction probably. The
      main pharmacodynamic ingredients of CCP-PC, 3-phenyl-2-propenal and
      Cinnamaldehyde were obviously higher contents than that of single CCP. It
      suggested that there exist certain interactions of the chemical ingredients in
      compound medicine rather than their sum effect of single medicines. There is a
      litter difference in quality and quantity between single medicines and pair
      medicines, so the application of pair medicines can expand single medicine's
      adaptive disease and has a good clinical referenced valuation.

PMID- 19160783
TI  - [Effects of penetration enhancers on percutaneous permeability of geniposide in
      Xiao'er Ninhuang tuire cataplasms].
AB  - OBJECTIVE: To investigate the different permeation enhancers on the transdermal
      permeation of Xiao'er Niuhuang tuire cataplasms (XNTC). METHOD: Using improved
      franz-type diffusion cell with excised rat skin in vitro as the transdermal
      barrier, the content of permeated geniposide was determined by HPLC to study the
      kinetic parameters such as cumulative permeation quantity and permeation rate.
      RESULT: The result showed that the process of penetrating of geniposide in XNTC
      through skin could be in accordance with zero-rade releasing equation and XNTC
      was stable during the course of experiment. CONCLUSION: 5% Propylene glycol (PG)
      azone (2:3) has the best permeation-enhancing effect, and the results provided a
      primary basis for the future research on Xiao'er Niuhuang tuire cataplasms.

PMID- 19160784
TI  - [Preparation of microparticles of SCF-CO2 extraction of Salvia miltiorrhiza by
      RESS].
AB  - OBJECTIVE: Application of rapid expansion of supercritical solution (RESS) in
      preparing micropaticles of SCF-CO2 extraction of Salvia miltiorrhiza. METHOD: The
      mixture which was composed of beta-cyclodextrin and SCF-CO2 extraction of S.
      miltiorrhiza with proportion 8:1 by weight, was granulated by RESS. The
      characteristics of the resululting particles were studied by scanning electron
      microscopy (SEM) and the assay of salviol IIA in particles which was determinated
      by HPLC. RESULT: The resulting particles were jacinth and photomicrograph
      produced by SEM showed that the morphology were silkiness and rugosity globular,
      the size distribution between 2 and 80 microm, and the contents of salviol IIA
      was 0.54%. CONCLUSION: The RESS method is applicable for preparing microparticles
      of SCF-CO2 extraction of S. miltiorrhiza and low operating temperature, simple
      processing, and no environmental pollution, and no residual solvent.

PMID- 19160785
TI  - [Studies on cyclodextrin inclusion complexes of Dragon's blood and its tablets
      preparation].
AB  - OBJECTIVE: To study the cyclodextrin inclusion complexes of Dragon's blood for
      improving the drug solubility and the preparation. METHOD: The inclusion
      complexes were prepared with beta-cyclodextrin, HP-beta-cyclodextrin, SBE-beta
      cyclodextrin and confirmed by DTA. The activity of the inclusion complex was
      tested by animal experiments. Inclusion complexes tablets were prepared and the
      dissolution test was performed. RESULT: The solubility of inclusion complexes was
      increased to 13. 75-168. 39 times. The activity of the inclusion complex was
      markedly improved, and dissolution rate was 78.69%. CONCLUSION: The cyclodextrin
      inclusion complexes of Dragon's blood have a good solubility, dissolution rate
      and pharmacological activity.

PMID- 19160786
TI  - [Studies on content determination and fingerprint of active constituents in
      different parts of cortex moutan].
AB  - OBJECTIVE: To determine the chemical constituents in different parts of Cortex
      Moutan, which can provides evidences to the processing techniques of Cortex
      Moutan. METHOD: The contents of paeonol, peoniflorin and fingerprints in
      different parts of Cortex Moutan were determined by HPLC. RESULT: Compareed with
      phloem, paeonol in cork is twice as many, but paeonol in duramen is half as many
      peoniflorin in cork is half and four times as many, peoniflorin in duramen is
      twice as many, the contents of active ingredients in duramen are high in
      fingerprint. CONCLUSION: If we only abandon the core, then we may get simple
      processings with the active ingredient contents increasing.

PMID- 19160787
TI  - [Content determination of epigoitrin in Radix Isatidis and its preparation by RP
      HPLC].
AB  - OBJECTIVE: To establish an HPLC method for the content determination of
      epigoitrin in Radix Isatidis and its preparation, and to provide valuable data
      for quality control of Radix Isatidis and its preparation. METHOD: The samples
      were separated on a ZORBAX SB-C18 (4. 6 mm x 150 mm, 5 microm) column with the
      mobile phase of acetonitrile-water-phosphoric acid-triethylamine (8.50 : 90.72 :
      0.73 : 0.05) in the flow rate of 0.7 mL x min(-1). The detection wavelength was
      set at 245 nm. Column temperature was 30 degrees C. RESULT: The linear range of
      epigoitrin was 0.0204-0.3060 microg (r = 0.9998), and the average recovery was
      98.99% with the RSD was 1.31% (n = 9). CONCLUSION: The method for quantitation of
      epigoitrin in Radix Isatidis and its preparation was accurate and reliable, which
      can be used to evaluate the quality of Radix Isatidis and its preparation.

PMID- 19160788
TI  - [Studies on constituents of rootsanel leaves from Desmodium blandum and their
      cytotoxic activity against growth of several tumor cells].
AB  - OBJECTIVE: To investigate the chemical constituents of Desmodium blandum and
      their cytotoxic activity against the growth of several tumor cells. METHOD:
      Various chromatographic techniques including silica gel, Sephadex LH-20 column
      chromatography were employed for the isolation and purification of the
      constituents. The structures of compounds were elucidated by spectral analyses
      (IR, UV, NMR, MS). Their cytotoxic activity was then studied. RESULT: Eight
      compounds were isolated from the stems of D. blandum and identified as N, N
      dimethyltryptamine (1), 5-methoxy-N, N-dimethyltryptamine (2), citrusinol (3),
      yukovanol (4), (Z)-1-(4-hydroxy-2, 3-dimethoxyphenyl)-3-(4-hydroxyphenyl) propene
      (5), (Z)-1-(3-hydroxy-2, 4-dimethoxy-phenyl)-3-(4-hydroxy-3-methoxy-phenyl)
      propene (6), methylprotocatechuate (7), katuranin (8). CONCLUSION: Among these
      compounds, compound 6 was isolated from D. blandum for the first time. In the MTT
      test, compounds 2 and 6 exhibit cytotoxic activities against the KB cell, and
      compounds 3 and 6 exhibit the same activities against the HepG2 cell.

PMID- 19160789
TI  - [Studies on ethyl acetate soluble constituents of Huanglian Jiedutang].
AB  - OBJECTIVE: To study the ethyl acetate soluble constituents from the water
      extractive of Huanglian Jiedutang decoction, which are composed of Rhizoma
      Coptidis, Radix Scutellariae, Cortex Phellodendri and Fructus Gardeniae, and
      provide substances foundation for its pharmacokinetic and pharmacodynamic
      investigation. METHOD: The chemical constituents were isolated by various column
      chromatographic methods and structurally elucidated by NMR and MS techniques.
      RESULT: Thirty-five compounds were isolated, among which twenty compounds have
      been identified as beta-sitosterol (1), oroxylin A (2), wogonin (3), ursolic acid
      (4), skullcapflavone I (5), tenaxin I (6), skullcapflavone II (7), limonin (8),
      5, 2'-dihydroxy-6, 7, 8, 3'-tetramethoxyflavone (9), chrysin (12), baicalein
      (17), tenaxin II (19), 5, 7, 2'-trihydroxy-6, 8-dimethoxyflavone (21),
      shihulimonin A (22), 6, 2'-dihydroxy-5, 7, 8, 6'-tetramethoxyflavone (26),
      viscidulin II (28), 5, 7, 4'-trihydroxy-8-methoxyflavone (29), 5, 7, 2', 6'
      tetrahydroxyflavone (30), wogonin-7-O-beta-D-glucuronide methyl ester (31) and
      daucosterol (34). CONCLUSION: On the basis of reported results of the chemical
      constituents of Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri and
      Fructus Gardeniae, it was estimated that all flavonoid compounds rised from the
      Radix Scutellariae, and compounds 8 and 22 rised from Cortex Phellodendri.
      Compound 22 was identified in the Cortex Phellodendri for the first time.

PMID- 19160790
TI  - [Studies on chemical constituents from leaves of Vaccinium bracteatum].
AB  - OBJECTIVE: To investigate the chemical constituents from the leaves of Vaccinium
      bracteatum. METHOD: Many column chromatographic techniques were used for the
      isolation and separation of chemical constituents. Their structures were
      elucidated on the basis of spectral analysis and chemical evidences. RESULT:
      Twelve compounds were isolated from the plant, and they were identified as
      chrysoeriol (1), scopoletin (2), trans-p-hydroxycinnamic acid (3), trans-p
      hydroxycinnamic acid ethyl ester (4), cafeic acid ethyl ester (5), beta
      sitosterol (6), iuteolin (7), quercetin (8), esculetin (9), cafeic acid (10),
      isolariciresinol-9-O-beta-D-xyloside (11), 10-O-trans-p-coumaroylsandoside (12).
      CONCLUSION: Compounds 4, 5, 11, 12 were isolated from the genus Vaccinium for the
      first time, and compounds 1, 2, 9, 10 were isolated from this plant for the first
      time.

PMID- 19160791
TI  - [Study on HPLC fingerprint of Prunella vulgaris].
AB  - OBJECTIVE: To establish HPLC fingerprint of Prunella vulgarise for quality
      control of the herbal medicine. METHOD: A sunfire C18 analytical column was used.
      The mobile phase A was 1% acetic acid, and mobile phase B was methanol. The
      elution was in gradient mode and detection wavelength was set at 290 nm. The flow
      rate was 1.0 mL x min(-1) and the column temperature at 30 degrees C. The
      analysis time was 60 min. RESULT: The similarity of 10 batches of P. vulgaris was
      not lower than 0.810. The fingerprints of the herbal medicine were classified P.
      vulgaris on the results of cluster analysis. CONCLUSION: This method is available
      for quality evaluation and control the quality of P. vulgaris.

PMID- 19160792
TI  - [HPLC fingerprint of Herba Senecionis Scandentis and its ESI-MS analysis].
AB  - OBJECTIVE: To study and establish the fingerprints of Herba Senecionis Scandentis
      by RP-HPLC and LC-MS. METHOD: C18 column was used in the HPLC separation. The
      mobile phase was composed of acetonitrile and 0.03% phosphoric acid with gradient
      elution. The flow rate was 1.0 mL m x min(-1) and detection wavelength was 254
      nm. RESULT: Under this selected chromatographic condition, good HPLC fingerprints
      of Senecio scandens were obtained. CONCLUSION: HPLC fingerprint facilitate the
      evaluation of the quality of Herba Senecionis Scandentis.

PMID- 19160793
TI  - [Study on safe use of 10% difenoconazole in GAP of Gentiana scabra].
AB  - OBJECTIVE: To investigate the safe use of 10% difenoconazole in planting Gentiana
      scabra. METHOD: The degradation dynamics of 10% ifenoconazole in the stems and
      leaves of G. scabra collecting in different time were determined by GC with ECD
      detection, and the half life of difenoconazole in the plant was calculated, and
      then the safe use method of 10% difenoconazole was formulated. RESULT: Under the
      local climatic conditions, the half life of 10% difenoconazole was 6.84-6.90
      days. CONCLUSION: In the good agricultural practice (GAP) of G. scabra, the
      maximal concentration of 10% difenoconazole is 400 g x ha(-1), the safety
      interval of using 10% difenoconazole is 40 days.

PMID- 19160794
TI  - [Quantitative analysis of two major secoiridoid glucosides in fruits of Ligustrum
      lucidum].
AB  - OBJECTIVE: To develop an HPLC method for determination of two major secoiridoid
      glucosides (nuezhenoside and G13) from Fructus Ligustri Lucidi. and determinae
      nuezhenoside and G13 in samples from different acquisition times and different
      places. METHOD: The sample was separated on a YMG-C18 (4.6 mm x 250 mm, 10
      microm) column. The mobile phase was acetonitrile-water, gradient elution (CH3CN:
      0 min, 20%; 15 min, 25%) with the flow rate of 1 mL x min(-1), the detection
      wavelength was 240 nm, and the column temperature was set at 25 degrees C.
      RESULT: In HPLC analysis ,the linear ranges of nuezhenoside and G13 were 0.341
      34.1 microg and 0.331-33.1 microg, respectively; their average recoveries were
      97.5% (RSD 1.35%) and 98.1% (RSD 1.82%), respectively. The results of content
      determination (nuezhenoside and G13) of samples from different places varied
      greatly. This may be caused by different species sources and different
      preparation methods, etc. The experiment led up to the fact that from the
      beginning to the middle of November the content of nuezhenoside and G13 reached
      the maximum. CONCLUSION: The established method can be used to determine two
      major secoiridoid glucosides (nuezhenoside and G13) in Fructus Ligustri Lucidi
      simultaneously. Meanwhile it can be used for the quality control of Fructus
      Ligustri Lucidi.

PMID- 19160795
TI  - [RP-hPLC determination of flavonoids in several flowers].
AB  - OBJECTIVE: To develvp a RP-HPLC method for the determination of flavonoids in
      fifteen kinds of flowers such as Iris lacteal pall, prunus persica and rosa
      chinensis. METHOD: The contents of quercetin, kaempferol and isorhamntin in
      fifteen kinds of flowers were extracted with methanol. The analysis was performed
      on a Kromasil C18 column (4.6 mm x250 mm, 5 microm) with methanol-0.1% phosphoric
      acid (50:50) as mobile phase. RESULT: The quercetin, kaempferol and isorhamntin
      were separated well, and the result shows that the content of quercetin in the
      Iris lactea Pall was the highest (1.536%), the contene of kaempferol in Persica
      persice was the highest (0.572%), and the content of isorhamntin in chrysamthemum
      morifolium was up to 0.290%. CONCLUSION: The contents of flavonoids in these
      flowers were by determined RP-HPLC for the first time and the method can be used
      for quantitative determination of flavonoids in the flowers.

PMID- 19160796
TI  - [Effects of berberine on expression of hepatocyte nuclear factor 4alpha and
      glucokinase activity in mouse primary hepatocytes].
AB  - OBJECTIVE: To observe the expression of hepatocyte nuclear factor 4alpha
      (HNF4alpha) and the activity of key enzyme glucokinase (GK) in glucose
      metabolism, and further to investigate the possible mechanism of berberine in
      treating type 2 diabetes. METHOD: Mouse primary hepatocytes were isolated by an
      improved single two-step perfusion method. The murine hepatocytes were cultured
      and incubated with berberine (0, 1, 3, 10, 30, 100 micromol x L(-1)) and 1 mmol x
      L(-1) metformin for 24 h respectively. The mRNA expression of HNF4alpha were
      quantified by RT-PCR and the protein expression of HNF4alpha were quantified by
      Western-blot. And the activity of GK were detected with enzyme kinetics method.
      RESULT: As compared with the negative control group, at a certain concentration
      range, the expression of HNF4alpha mRNA and protein and the activity of GK were
      promoted by berberine. Both of them reached the top at the concentration of 30
      micromol x L(-1) (P<0.01). But the metformin made no difference with the negative
      control group on the expression of HNF4alpha and the activity of GK. CONCLUSION:
      It is suggested that the effects of berberine on improving glucose metabolism can
      be mechanically associated with its up-regulating the HNF4a expression and
      inducing the activity of hepatic glucokinase.

PMID- 19160797
TI  - [Morroniside inhibits H2O2-induced apoptosis in cultured nerve cells].
AB  - OBJECTIVE: To investigate the effects of morroniside on H2O2-induced apoptosis in
      nerve cells. METHOD: Human neuroblastoma cell line SH-SY5Y cells were pre
      incubaed with morroniside (1, 10, and 100 micromol x L(-1)) for 24 h prior to
      exposure to H2O2 (500 micromol x L(-1)) for 18 h. The activity of reactive SOD
      was measured by a biochemical assay. The expression of caspase-3, caspase-9, Bcl
      2 and Bax was determined by Wastern blotting method. RESULT: Pretreatment of the
      cells with morroniside (10 and 100 micromol x L(-1)) increasd SOD activity by 14%
      (P<0.01) and 11% (P<0.05) in comparison with cells exposed only to H2O2.
      Morroniside (1, 10, 100 micromol x L(-1)) lowered caspase-3 level by 31%
      (P<0.01), 103% (P<0.001) and 95% (P<0.001), decreased caspase-9 content by 71%
      (P<0.001), 132% (P<0.001) and 37% (P<0.05), and increasd Bcl-1 level by 88%
      (P<0.01), 121% (P<0.001) and 60% (P<0.01) respectively but no significant change
      occurred in Bax level in comparison with cells exposed only to H2O2. CONCLUSION:
      Morroniside has neuroprotection effect against H2O2-induced oxidation injury in
      nerve cell.

PMID- 19160798
TI  - [Effect of nobiletin on tubulin polymerization in vitro].
AB  - OBJECTIVE: To investigate the possible mechanisms of nobiletin for anticancer by
      studying the inhibition effects of nobiletin on tubulin polymerization. METHOD:
      In vitro nobiletin was added into the tubulin polymerization-depolymerization
      system and the absorption values were recorded at 350 nm under 37 degrees C.
      RESULT: As compared with controls, the absorption values in reaction system
      decreased significantly in nobiletin treatment groups. When nobiletin final
      concentrations in reaction system were 5.0, 7.5, 10.0 and 12.5 micromol x L(-1),
      the maximum absorption values were 0 130, 0.109, 0.086 and 0.071 with 16.7%,
      30.1%, 44.9% and 54.5% of inhibition rate, respectively. The results suggested
      that nobiletin could inhibit tubulin polymerization. CONCLUSION: The inhibition
      effect of nobiletin on tubulin polymerization is the possible mechanism for
      anticancer.

PMID- 19160799
TI  - [Effect of ginsenoside Rh2 on transplanted-tumor and expression of JAM in mice].
AB  - OBJECTIVE: To discuss the anti-tumor activity of ginsenoside Rh2, we observed the
      expressions of the junction adhesion molecul (JAM) in transplanted-tumor in mice.
      METHOD: The models of 40 transplanted-tumor mice that were established by
      subsequently injecting cancer ascite of mice (S180) with 0.2 mL per mouse into
      the preepipodite skin were divided into two groups. Experiment group was drenched
      with 2 mL ginsenoside Rh2 per mouse, equating to a dose 20 mg x kg(-1). Control
      group was drenched with 2 mL normal saline per mouse. The expression of JAM-1,
      JAM-2 in the lymphatics, blood vessels and tumours were observed by
      immunohistochemical staining. RESULT: The expression of JAM-1 on the cancer cells
      was significantly decreased in experiment group (IA 340.55) as compared with
      control group (IA 549.90, P<0.05). However, JAM-2 weakly expressed in both two
      groups. The density of blood vessels in which JAM-1, JAM-2 expressed showed 2.33
      and 1.34 in control group, and 1.09 and 0.9 in experiment group respectively.
      Moreove, the density of lymph vessels were respectively 2.23 and 1.88 in control
      group compared with 0.99 and 0.79 in experiment group. The expression in blood
      vessels and lymph vessels in control group were significantly higher than those
      in experiment group, respectively (P<0.05). CONCLUSION: Ginsenoside Rh2 can
      affect the tumor growth, further angiogenesis and lymphangiogenesis by down
      regulating JAM expression in tumor.

PMID- 19160800
TI  - [Effect of selenium-protein polysaccharide extracted from Se-rich Cordyceps
      militaris on tumor-bearing mice].
AB  - OBJECTIVE: To extract and analysis the active components of Se-protein
      polysaccharide from Se-rich Cordyceps militaris, and to discuss the anti-tumor
      effect of Se-protein polysaccharide. METHOD: Protein, polysaccharides and
      selenium content were determined by the methods of Folin-phenol reagent (lowry),
      phenol-sulfate and DAN fluorescence, respectively. Tumor-bearing mouse model was
      established and divided into the model group, cyclophosphamide group, cordyceps
      high and low dosage group (200, 100 mg x kg(-1)). Then the Se-protein
      polysaccharide's anti-tumor activity and immune function in vivo were observed by
      compare with model group in the weight of mice, inhibitory rate, conversion rate
      of peripheral blood lymphocytes, dissection index K, swallowed factor alpha,
      liver and spleen factor coefficient, GSH-Px and SOD activity and the content of
      MDA. RESULT: Se-protein polysaccharides from Se-rich Cordyceps militaris had a
      significant anti-tumor action with the inhibitory rate 46.92% and could avoid
      toxic effect of chemotherapy drug like cyclophosphamide. It also could enhance
      immune function and body antioxidant capacity by inhibiting the decline of tumor
      bearing mouse liver coefficient and spleen coefficient in tumor-bearing mice
      caused by cyclophosphamide. CONCLUSION: Se-protein polysaccharide, the extraction
      of Se-rich Cordyceps militaris's can inhibit tumor grouth of tumor-bearing mouse.

PMID- 19160801
TI  - [Development of virulent heat-evil-induced thrombosis animal model].
AB  - OBJECTIVE: To develop a virulent heat-evil-induced thrombosis animal model, and
      provide a rational animal model for pathogeny and pathogenesis research of
      thrombosis-related diseases, anti-thrombosis activity screening and pre-clinical
      studies of CAHT formula. METHOD: SD rats were pretreated with carrageenin (Ca)
      intraperitoneal injection, followed by intravenous injection of endotoxin (LPS
      from E. coli O111:B4) 50 microg x kg(-1) 16 h later. Thrombosis in rat tails were
      observed during 12-24 h after injection of LPS. The inflammatory mechanism of
      this model were investigated by analyzing serum level of TNF-alpha, IL-6, TXB2
      and 6-keto-PGF 1alpha, CD11b/CD18 expression of white blood cells (WBC) and P
      selectin expression of vessel walls. RESULT: In LPS/Ca model group, thrombosis
      can be clearly observed in the distal part of rat tails after 12-24 h of LPS/Ca
      treatment. High level of TNF-alpha and IL-6 can be measured in serum. The
      expression of CD11b/CD18 in WBC and P-selectin in vessel endothelium
      significantly increased and the number of WBC in peripheral blood markedly
      decreased shortly after LPS/Ca treatment. The adherence of white blood cells to
      vessel endothelium which can be seen by microscope mainly contributed to the
      decrease of WBC. The results indicated that there was obvious inflammation after
      treatment with LPS/Ca, suggesting that inflammation was the key mechanism for
      this model. CONCLUSION: This model was developed through treatment of LPS in
      combination with Ca, of which LPS is considered to be an exotic virulent heat
      evil in TCM, while the inflammatory molecules produced in this model, such as TNF
      alpha, IL-6, CD11b/CD18 and P-selectin belong to internal virulent heat-evils, so
      this animal model consists of pathogeny and pathogenesis of virulent heat-evils.
      virulent heat-evil.

PMID- 19160802
TI  - [Effects of Shenqi Bufei Tang on expessions of NF-kappaB, MMP-9 and TIMP-1 in
      airway remodeling of COPD rat model with lung-Qi deficiency syndrome].
AB  - OBJECTIVE: To observe the effects of Jiajian Bufei Tang on expessions of nuclear
      factor-kappaB (NF-kappaB), metalloproteinase (MMP-9) and tissue inhibitor of
      metalloproteinase-1 (TIMP-1) in the airway remodeling of COPD rat model with lung
      Qi deficiency syndrome. METHOD: Make quantitative stimulation with tobacco, SO2
      and papin to establish COPD rat model with lung-Qi deficiency syndrome. Sixty
      male rats were randomly divided into: normal group (N), model group (M), low dose
      treatment group (LT), medium dose treatment group (MT), high dose treatment group
      (HT), and glucocorticoid treatment group (GCT). To observe the lung
      histopathological features. To measure the thinknesses of the airway wall and
      smooth muscle layer of the small airway by means of image analyzer, The NF-kappaB
      activity and the protein expressions of MMP-9 and TIMP-1 were examined by
      immunohistochemical analysis. RESULT: The NF-kappaB activity and the protein
      expressions of MMP-9 and TIMP-1 in brouch and lung and the thinknesses of the
      airway wall and smooth muscle layer in the M group were significanthly higher
      than those in the N group (P<0.01). After treatment, the NF-kappaB activity and
      the protein expressions of MMP-9 in the HT, MT and GCT group were lower than
      those in the M group (P<0.01), the GCT group was better than the HT, MT group.
      The protein expressions of TIMP-1 in HT, MTgroup were lower than that in the M
      group. The thinknesses of the airway wall and smooth muscle layer were lower in
      the HT group than those in the M group (P<0.05). CONCLUSION: Shenqi Bufei Tang
      may downregulate the NF-kappaB activity and the protein expressions of MMP-9 and
      TIMP-1 and intervene in the airway remodeling of COPD rat model with lung-Qi
      deficiency syndrome.

PMID- 19160803
TI  - [Effects of Yuquan pills on pharmacokinetics of metformin hydrochloride in
      diabetic rats].
AB  - OBJECTIVE: To study effects of Yuquan pills on the pharmacokinetics process of
      metformin hydrochloride in diabetic rats. METHOD: After administration Yuquan
      pills 7 day to the diabetic rats, the metformin hydrochloride was orally
      administrated, then the blood samples were collected at different time. The
      concentrations of metformin hydrochloride in plasma were determined by HPLC
      method and the pharmacokinetic parameters were calculated. RESULT: The
      pharmacokinetic parameter Cmax of the controlling group and the testing group
      were respectively, 18.95, 21.76 mg x L(-1); t1/2 were 1,069.8, 1,767.4 min,
      respectively; CL/F were 0.013, 0.008 L x min(-1) x kg(-1); AUC were 10,042.1,
      10,712.2 mg z L(-1) x min(-1) respectively. CONCLUSION: The pharmacokinetics
      process of metformin hydrochloride in diabetic rats fits one-compartment model.
      Yuquan pills has a significant effect on the pharmacokinetics of metformin
      hydrochloride in diabetic rats.

PMID- 19160804
TI  - [Study on other measuring units of Chinese medicine in Sui and Tang dynasties].
AB  - Besides the changes in weight measuring units, the other units also changed.
      "Larger and smaller liter" affected traditional Chinese medicine. Length
      measuring units was little used, and the irregular measuring units such as
      imitate units, quantity units, and assessing units remained in some extent.
      Because the regular measuring units gradually replaced the irregular ones, some
      doctors made investigates to the conversion of these measuring units.

PMID- 19160805
TI  - [Isolation and identification of a thermophilic bacterium from hot springs in
      Changbai Mountains].
AB  - OBJECTIVE: We studied physiological and biochemical properties of a thermophilic
      bacterium isolated from hot springs in Changbai Mountain. METHODS: The strain CBS
      5 (=JCM 15484) from hot springs in Changbai Mountains was isolated by plating and
      screening on Olive-rich medium. It was characterized by the physiological and
      biochemical analysis, 16S rDNA sequencing and determination of (G+C)mol%
      contents. RESULTS: The cells were Gram-positive, non-motile rods, spore-forming
      and generally occurred singly or in pairs. The growth temperature ranges from 48
      degrees C to 70 degrees C, optimum at 65 degrees C; growth pH ranges from 6.5 to
      8.5, optimum at 7.7. The strain used glucose, sucrose, maltose, lactose and
      rhanmose as carbon and energy sources. The G+C content of DNA was 41.9 mol%. The
      major cellular fatty acids were iso-C15:0, C16:0 and iso-C17:0, respectively
      representing about 24.20%, 20.45% and 17.42% of total fatty acids. The 16S rDNA
      sequence analysis showed that the strain belonged to the Anoxybacillus genus, for
      the sequence similarity was 95.1%-98.5% to other known species of Anoxybacillus.
      CONCLUSION: Strain CBS-5 was a member of Anoxybacillus.

PMID- 19160806
TI  - [Distribution of avian influenza virus subtypes among domestic ducks in eastern
      China].
AB  - OBJECTIVE: To identify the distribution of avian influenza virus subtypes among
      domestic ducks in eastern China. METHODS: One hundred and eighty avian influenza
      viruses isolated from domestic ducks between 2002 and 2006 were tested for their
      Hemagglutinin subtypes, and 88 of them were followed by monitoring for
      Neuraminidase (NA) subtypes. RESULTS: At least 9 HA subtypes and 6 NA subtypes,
      which constituted 13 subtypes of avian influenza viruses in domestic ducks,
      including H1N1, H3N1, H3N2, H3N8, H4N6, H5N1, H5N2, H6N2, H6N8, H8N4, H9N2, H10N3
      and H11N2, were circulating in eastern China in recent years. CONCLUSION:
      Multiple subtypes of avian influenza viruses were distributed among domestic
      ducks in eastern China in recent years. The surveillance and prevention of avian
      influenza viruses in domestic ducks must be strengthened.

PMID- 19160807
TI  - [Complete nucleotide sequence and analysis of Planobispora linear plasmid pPR2].
AB  - OBJECTIVE: To obtain the complete nucleotide sequence of Planobispora linear
      plasmid pPR2, and reveal the novel telomere replication protein and possible
      replication loci from the centrally located origin. METHODS: We cloned the EcoRI
      DNA fragments and assembled them to get the whole sequence of pPR2. We analyzed
      the secondary structure of the telomere DNA and the putative telomere replication
      protein using software, and detected the possible replication loci by
      Streptomyces protoplast transformation. RESULTS: The complete nucleotide sequence
      of pPR2 consists of 15520 bp in length, with a 68.1% (G+C) content. The 329 bp
      terminal inverted repeat sequence can't form the conserved fold-back secondary
      structure as that of many Streptomyces linear replicons. Lacking of typical
      Streptomyces tap/tpg locus for telomere replication, pPR2.3c encodes a protein
      with two domains resembling the telomere associated protein of Streptomyces and
      helicase of Haemophilus respectively. No typical Streptomyces iteron-rep locus
      for replication from the centrally located origin, two DNA fragments containing
      almost all pPR2 were cloned and introduced by transformation into S. lividans
      ZX7, but no transformants were obtained. pPR2 encodes single-strand binding
      protein which may regulate replication of linear DNA and Tra protein for
      conjugation transfer in actinomycetes. CONCLUSION: pPR2 is the smallest
      actinomycete linear plasmid beyond Streptomyces. This is the first time to report
      the complete nucleotide sequence of linear plasmid in the genus Planobispora.
      pPR2 may have novel mechanism for telomere replication, and pPR2.2c and pPR2.3c
      encode the possible telomere replication proteins.

PMID- 19160808
TI  - [Construction and stress tolerance of trehalase mutant in Saccharomyces
      cerevisiae].
AB  - OBJECTIVE: Accumulation of trehalose is critical in improving the stress
      tolerance of Saccharomyces cerevisiae. Two enzymes are capable of hydrolyzing
      trehalose: a neutral trehalase (NTH1) and an acidic trehalase (ATH1). We
      constructed trehalase disruption mutants to provide a basis for future commercial
      application. METHODS: To retain the accumulation of trehalose in yeast cell, we
      constructed diploid homozygous neutral trehalase mutants (Deltanth1), acid
      trehalase mutants (Deltaath1) and double mutants (Deltaath1Deltanth1) by using
      gene disruption. We tested mutants'trehalose content and their tolerance to
      freezing, heat, high-sugar and ethanol concentrations. RESULTS: These trehalase
      disruption mutants were further confirmed by PCR amplification and southern blot.
      All mutant strains accumulated higher levels of cellular trehalose and grew to a
      higher cell density than the isogenic parent strain. In addition, the levels of
      trehalose in these mutants correlated with increased tolerance to freezing, heat,
      high-sugar and ethanol concentration. CONCLUSION: The improved tolerance of
      trehalase mutants may make them useful in commercial applications, including
      baking and brewing protein.

PMID- 19160809
TI  - [Construction and function analysis of the Epstein-Barr virus-encoded latent
      membrane protein-1 of CTAR3 region].
AB  - OBJECTIVE: The role of carboxyl terminal activating region of latent membrane
      protein1 (LMP1) in Epstein-Barr virus infection and oncogenesis is unclear. In
      this study, we investigated the activating sites and functionary mechanism of
      LMP1. METHODS: We recombined a deletion mutant type LMP1 (LMP1Delta232-351),
      deleted the amino acid residues including 232-351 codons in carboxyl terminal
      activating region-3 by PCR. Then we compared mutant type LMP1Delta232-351 with
      wild type LMP1 (LMP1WT) to alter biological effect in Nasopharyngeal Epithelial
      Cell line NP69. Moreover, we constructed a Janus Kinase 3 (JKA3) promoter
      luciferase reporter system (pGL-2/JAK3-LUC). We respectively cotransfected the
      LMP1Delta232-351 and LMP1WT with promoter including NF-kappaB binding sequence or
      JAK3 promoter luciferase reporter into 293 cells (controlled with pLNSX vector),
      and compared their actions to activating promoters by results of luciferase
      activity assay. RESULTS: (1) The colony forming number (CFN) of NP69-LMP1Delta232
      351 cells significantly decreased to compare with CFN of NP69-LMP1WT (n=3,
      p<0.01). (2) LMP1WT was able to up-regulate the transcription activity of JAK3
      promoter and the level of up-regulation was correlated with its concentration in
      Human embryonic kidney 293 cell line; while LMP1Delta232-351 was almost defective
      ability to activate the promoter. CONCLUSION: The carboxyl terminal activating
      region-3 may be one of the most important function sites of LMP1, which involved
      in activating the JAK3 promoter and regulating the expression of JAK3 protein.

PMID- 19160810
TI  - [Recombinant expression of an autoinducer synthase of Sinorhizobium sp.1128 in
      Escherichia coli].
AB  - OBJECTIVE: To explore the roles of quorum sensing system in establishing
      symbiosis between bacterium Sinorhizobium sp.1128 and its plant host Melilotus
      suaveolens Ledeb. METHODS: According to homologous analysis, we designed primers
      to amplify the autoinducer synthase encoding genes in Sinorhizobium sp.1128
      according to Sinorhizobium medicae WSM419 genome sequences. The autoinducer
      synthase encoding genes were cloned into the expression vector of pYC12 and
      expressed in E. coli DH5alpha. Thin-layer chromatography (TLC) assay was used to
      study their roles in autoinducer production. A duplicated inactivation of the
      gene was used to explore its function in plant nodulation. RESULTS: Homologous
      analysis showed that at least three annotated acylated homoserine lactone (AHL)
      synthase genes existed in Sinorhizobium medicae WSM419 genome. We cloned these
      three autoinducer synthase genes in Sinorhizobium sp.1128. One of these genes
      named traI2 was over expressed in E. coli DH5alpha. At least two different AHLs
      were produced by the recombinant strain. Disruption of traI2 reduced both the
      autoinducers (AI) activities and AHL production by TLC detection. Furthermore,
      the complementation of traI2 reverted the phenotype of AI activities. These
      findings demonstrate that traI2 was responsible for AI synthesis in Sinorhizobium
      sp.1128. More important, the traI2 deficient strains were defective in nodule
      formation on their host plant. CONCLUSION: The quorum sensing circuits in
      Sinorhizobium sp.1128 may play an important role in symbiosis between plant and
      bacterium.

PMID- 19160811
TI  - [Influence of culture medium on the viability and membrane fatty acid composition
      of Oenococcus oeni SD-2a].
AB  - OBJECTIVE: To achieve the high quality of malo-lactic starter cultures, we
      investigated the effect of three culture media on the direct inoculation
      viability, freeze-drying viability and membrane fatty acid composition of
      Oenococcus Oeni SD-2a. METHODS: We monitored the bacterial growth and change in
      medium pH when O. oeni SD-2a cells were cultured in ATB, FMATB and MATB media. O.
      oeni SD-2a cells in early stationary phase were harvested, and subjected to
      direct inoculation experiments and freeze-drying processes. Then we determined
      inoculation and freeze-drying viability. Membrane fatty acid composition of those
      corresponding O. oeni SD-2a cells was determined by GC/MS method. RESULTS: The
      results showed ATB medium without supplementation of DL-malate had weak pH
      buffering capability. Compared with FMATB and MATB, O. oeni cells cultured in ATB
      increased inoculation viability and freeze-drying viability. Concerning the
      membrane fatty acid composition, it was observed that ATB medium increased
      distinctly the relative concentration of lactobacillic acid (C19cyc11) and U/S
      (the unsaturated: saturated fatty acid) ratio in cell membrane lipid composition
      of O. oeni SD-2a. CONCLUSION: The increased resistance to wine stressor and
      freeze-drying was probably a result of the cross protection conferred by self
      acid stress response induced in ATB medium, which might be related with changes
      in membrane fatty acid composition of O.oeniSD-2a. Therefore, ATB medium was more
      suitable for preparation of O. oeni SD-2a commercial starter cultures.

PMID- 19160812
TI  - [Expression and characterization of chaperonin from Sulfolobus solfataricus P2].
AB  - OBJECTIVE: To elucidate the structure and functional mechanism of beta subunit of
      chaperonin from the thermoacidophilic archaeon Sulfolobus solfataricus P2.
      METHODS: Molecular cloning of the beta subunit gene of chaperonin from the
      thermoacidophilic archaeon Sulfolobus solfataricus P2 was performed by using PCR
      technique. The gene was expressed in BL21 (DE3) of Escherichia coli. After
      purified and assembled in vitro, the structure of the beta subunit homo-oligomer
      was observed by transmission electron microscope (TEM). The function of this homo
      oligomer as a chaperonin was evaluated. RESULTS: The gene encoding beta subunit
      of chaperonin was amplified by PCR from the genomic DNA of Sulfolobus
      solfataricus P2 and expressed in BL21 (DE3) of E. coli. In vitro, the purified
      beta monomer could assemble to a homo-oligomer in the presence of ATP and Mg2+.
      As observed by transmission electron microscope(TEM), the beta subunit homo
      oligomer (beta16mer) showed a double-ring structure, which is typical in group II
      chaperonins. The optimum temperature for ATPase activity of the beta16mer was 80
      degrees C. The beta16mer was able to promote the refolding of denatured GFP and
      improve the thermostability of xylanase. CONCLUSION: According to the prediction
      and analysis of the chaperonin sequence from thermoacidophilic archaeon
      Sulfolobus solfataricus P2 genome, we cloned and expressed the beta subunit of
      chaperonin from P2. This subunit formed a homo-oligomer in vitro and showed a
      typical structure of group II chaperonins. We found that the beta16mer was able
      to function correctly when promoting the refolding and improving the
      thermostability of some other proteins. Our research has laid a foundation for
      the further study on the molecular mechanism of thermoacidophilic archaeon.

PMID- 19160813
TI  - [Analysis of acid-phosphatase localization in Aspergillus fumigatus by a secreted
      chimeric green fluorescent protein as reporter].
AB  - OBJECTIVE: In yeast glycosylphosphatidylinositol (GPI) anchoring is a signal
      directing localization of GPI proteins to the plasma membrane or cell wall. Some
      of the cis-requirements for the localization of GPI proteins are now understood,
      however, little is known the signals directing distribution of the GPI proteins
      in filamentous fungi. Previously, AfPhoA, a GPI-anchored acid phosphatase in
      filamentous fungus Aspergillus fumigatus, was first isolated from the cell
      membrane and latter found to be associated with the cell wall. The actual
      distribution of the AfPhoA remains unclear. Meanwhile, the signature amino acid
      motif that determines the distribution of GPI protein in yeast is not found in
      the C-terminal sequence of the AfPhoA. We aimed to elucidate the cell
      distribution of the AfPhoA. METHODS: The green fluorescent protein (GFP) was used
      as reporter to track the localization of the AfPhoA. The C-terminal sequence of
      the AfPhoA was fused to the C-terminus of the GFP. RESULTS: We first constructed
      the expression plasmid pchiGFP, in which the N-terminal signal sequence of the A.
      fumigatus AfChiB1 was fused to the N-terminus of the GFP. After transformation, a
      secreted expression of the GFP was achieved in A. fumigatus. Based on this
      construct, The C-terminal sequence of the AfPhoA was fused to the C-terminus of
      the GFP to construct a chimeric GFP. After the co-transformation of the fusion
      construct with plasmid pCDA14, a transformant was confirmed to harbor the
      chimeric GFP in its genome and could express the chimeric GFP. The transformant
      cultivated with or without chitin induction could express the chimeric GFP mainly
      attached to the cell membrane, a prolonged cultivation led to a minor
      distribution of the chimeric GFP in the cell wall. Although a 30KD of GFP
      fragment, instead of an intact 43.5KDa chimeric GFP, was also detected in the
      culture supernatant, which might be released by the cleavage between the fusion
      protein and its GPI anchor. CONCLUSION: Our results suggest that GPI anchoring
      determines the distribution of the AfPhoA in the cell membrane. In addition to
      our investigation of the GPI anchoring, an expression vector was also
      constructed, which would be useful for analyses of the function and regulation of
      the genes and proteins in A. fumigatus.

PMID- 19160814
TI  - [Cloning, expression and characterization of a heterodimeric beta-galactosidase
      from Lactobacillus acidophilus ATCC 4356].
AB  - Heterodimeric beta-galactosidase of Lactobacillus acidophilus belongs to
      glycoside hydrolase family 2, encoded by two overlapping and translational
      coupling genes, lacL and lacM. The lacL and lacM genes of the sequenced strain L.
      acidophilus NCFM encode polypeptides with calculated molecular masses of 73,253
      and 35,817 Da, respectively. OBJECTIVE: To clone, overexpress and characterize
      the enzyme in Escherichia coli. METHODS: We cloned the fragment (2834 bp)
      containing ribose-binding site (RBS) and coding regions of the lacLM genes from
      L. acidophilus ATCC 4356 into expression vector pQE31. RBS and HIS-Tag of pQE31
      were substituted by inserted fragment. Recombinant plasmid was electrotransformed
      into E. coli JM109. Expression product was purified by ammonium sulphate
      fractionation, anion-exchange, affinity chromatography and gel permeation. Native
      molecular mass of homogenous enzyme was measured by gel permeation, and beta
      galactosidase activity was determined by using o-nitrophenyl-beta-D
      galactopyranoside (ONPG) as the substrate. RESULTS: Overexpression of the soluble
      enzyme in E. coli was achieved. Amino acid residue 512 of recombinant LacL was
      different from that of L. acidophilus NCFM. Homogenous enzyme was obtained by
      purification. The homogenous enzyme had a specific activity of 226 U/mg protein,
      a native molecular mass of 96.3+/-4.6 kDa, an optimum temperature at 49 degrees C
      and an optimum pH of 7. The Km and Vmax values of the enzyme were 2.18+/-0.12
      mmol/L, 273+/-5 U/mg protein respectively.

PMID- 19160815
TI  - [Analysis of soil bacterial diversity by using the 16S rRNA gene library].
AB  - OBJECTIVE: Soil microorganisms play an important role in the vegetable soil
      ecosystem. Through 16S rRNA gene cloning library technology to analysis the
      composition of bacteria community structure in the typical vegetable soil. To
      revealed the microbial diversity in the typical vegetable soil, and laid the
      foundation for the relationship between land-use changed and the ecological
      environment. METHODS: Total microbial DNA was directly extracted from a typical
      vegetable soil of Beijing and Shandong province. The clone library of 16S
      ribosomal RNA genes was amplified using PCR with universal bacterial primer sets.
      The PCR products were then subcloned into pGEM-T vector. Each unique restriction
      fragment polymorphism pattern, created by using two restriction endonucleases
      (Hinf I and Hae III), was designated as an operational taxonomic unit (OTU).
      Amplified DNA was used for diversity analysis. RESULTS: Constructed bacterial
      phylogenetic trees of the samples revealed the gamma-proteobacteria, beta
      proteobacteria and alpha-proteobacteria groups were dominant in both clone
      libraries. Bacterial species composition from Beijing and Shandong province
      included 124 OTUs and 92 OTUs, respectively. CONCLUSION: The dominant species of
      bacteria populations are proteobacteria in the typical vegetable soil of Beijing
      and Shandong areas. But bacterial diversity in the two typical vegetable soil
      samples was reduced. This phenomenon may be directly related to continuous
      cultivation for many years and plant a single vegetable species. At the same
      time, this phenomenon may also be an important reason to cause vegetable soil
      diseases widespread occurred and soil degradation.

PMID- 19160816
TI  - [Enrichment and diversity analyis of arsenite-resistant bacteria in deep sea
      sediment samples from southwest Indian Ocean ridge].
AB  - OBJECTIVE: The aim of this study was to assess the diversity of arsenite
      resistant bacteria in deep sea sediment of the southwest Indian Ocean Ridge.
      METHOD: Arsenite-resistant bacteria in the deep-sea sediment were enriched with 2
      x 10(-3) mol/L NaAsO2 and isolated on plates. Their diversity was further
      examined by Denaturing gradient gel electrophoresis (DGGE) and 16S rDNA library
      analysis. Furthermore, the gene encoding putative arsenite efflux pump was
      detected with degenerate primers among these isolates. RESULT: Eight arsenite
      resistant isolates were obtained; they belonged to five different genera of gamma
      proteobacteria. One isolate named As-I1-3 can grow in presence of 26 x 10(-3)
      mol/L NaAsO2, showed highest similarity to Pseudoalteromonas tetraodonis IAM
      (100%). DGGE result showed that As-I1-3 was dominant in arsenite enriched
      community, followed by isolate As-I1-5 (Halomonas meridiana, 100%) and Mn-I1-6
      (Marinobacter vinifirmus, 99%). 16S rDNA library analysis reconfirmed the result
      of DGGE, which showed that the three bacteria occupied 72.5%, 10% and 7.5% of the
      total OTUs (operational taxonomic units), respectively. However, only from other
      two isolates which were not dominant, the gene encoding a putative arsenite
      efflux pump was obtained. CONCLUSION: Different bacteria of arsenite-resistance
      inhabited in deep sea environment, among which P. tetraodonis (100%) showed
      highest resistance; they might play a certain role in the geobiocycling of
      arsenic element in marine environments.

PMID- 19160817
TI  - [Resistant mechanism of Fusarium graminearum against carbendazim, unrelative to
      alpha2-tubulin gene].
AB  - OBJECTIVE: We studied the resistance of Fusarium graminearum against carbendazim,
      to confirm if the resistance was related to the whole nucleotide sequence of
      alpha2-tubulin. METHODS: The whole nucleotide sequence of alpha2-tubulin and
      morphological characteristic were analyzed from different sensitivie strains when
      treated with carbendazim. RESULTS: The results indicated that both sensitive
      strains and moderately resistant strains produced tube with swelled abnormality
      or germlings with more branches or cells of conidium swelled greatly, when
      treated with carbendazim at their EC50 or EC90. The full-length nucleotide
      sequence of alpha2-tubulin gene from each of 8 F. graminearum strains from China,
      which had different carbendazim (MBC) sensitivity phenotypes, were separated by
      using PCR with 4 primer sets designed in accordance with nucleotide sequence of
      the gene from the genomic sequencing strain, NRRL 31084 (PH-1). The DNA sequence
      comparison showed no difference in the nucleotide sequence of alpha2-tubulin gene
      among 4 sensitive and 4 resistant strains. This result demonstrates that there
      was no relationship between MBC-resistance and alpha2-tubulin gene. The full
      length of the gene spanned 1712 bp, including 4 introns, encoding 453 amino
      acids. With 100% homology, there were 5 nucleotide differences in alpha2-tubulin
      gene between PH-1 isolate and the 6 strains from China. The homology of the
      deduced amino acid sequence of the gene was 100% among the 6 strains and PH-1
      isolate, and 64%-89% among other 9 species of fungi. CONCLUSION: The resistance
      of F. graminearum against carbendazim was irrelative to the nucleotide sequence
      of alpha2-tubulin.

PMID- 19160818
TI  - [Purification and structural identification of herbicides from Botrytis cinerea].
AB  - OBJECTIVE: Toxin produced by phytopathogenic fungi is one of the important
      microbial herbicides. We found a new compound with herbicidal activity. METHODS:
      Five different ultraviolet absorption components were isolated from the filtrate
      of Botrytis cinerea isolate 7-3 culture. RESULTS: Of the five components, one
      showed strong inhibitory to Digitaria sanguinalis. The pure fraction with high
      herbicidal activity was obtained by HPLC purification. Its structure was
      identified as 10-syn-dihydrobotrydial by Ultraviolet and Visible Spectroscopy,
      Infrared Spectrum, Nuclear Magnetic Resonance Spectroscopy analysis. CONCLUSION:
      The findings are important for future preparation and application of the
      herbicide.

PMID- 19160819
TI  - [Analysis of molecular biological characteristic of the gene and its flanking
      sequences, similar with transposase in Vibrio cholerae pathogenicity island,
      among V. alginolyticus strains].
AB  - OBJECTIVE: To investigate whether the gene similar with transposase gene (vpiT)
      from pathogenicity island of Vibrio cholerae exists in V. alginolyticus strains,
      and to analyze molecular biological characteristic of the gene and its flanking
      sequences. METHODS: PCR detection of the gene, similar with vpiT in pathogenicity
      island of V. cholerae was done among 94 strains of V. alginolyticus. PCR products
      from positive strains were directly sequenced. Based on acquired partial
      sequences, we designed primers for reverse PCR, and got the amplification
      fragment containing complete gene (valT) from V. alginolyticus E0601, which was
      similar with vpiT gene. The reverse PCR product was cloned and sequenced, and the
      acquired sequence was analyzed with bioinformatic methods. RESULTS: We found that
      among 94 V. alginolyticus strains, only V. alginolyticus E0601 and E0612, from
      east coastal areas of Guangdong province, produced predicted positive
      amplification fragments in PCR detection. Sequencing indicated that amplification
      fragments from V. alginolyticus E0601 and E0612 had identical DNA sequence (named
      valT-S1). Sequence valT-S3 from V. alginolyticus E0601, containing complete valT
      gene and flanking segments, was finally obtained through reverse PCR, cloning,
      and sequencing. Bioinformatic analysis on valT-S3 suggested that valT was
      transposase gene, highly similar with vpiT in V. cholerae VPI. CONCLUSION:
      According to above result and related references, we believe that valT and its
      flanking segments were acquired from heterogenous bacteria, and VPI or its
      component probably transfers among Vibrio species including V. alginolyticus.

PMID- 19160820
TI  - [Isolation and characterization of bacteriophages of Enterobacter sakazakii].
AB  - OBJECTIVE: To isolate bacteriophage of Enterobacter sakazaki from sewage using
      reference and isolated strains as indicators, and to observe the biological
      characteristics of the bacteriophage. METHODS: Bacteriophages were isolated from
      sewage with double layer agar. Specificity and host ranges of the bacteriophages
      were determined by reference bacterium from same genus and family. Phage
      particles were observed by electron microscope and its molecular character was
      analyzed by Random amplified polymorphic DNA. RESULTS: Five bacteriophages of E.
      sakazakii were isolated from sewage and showed relatively narrow host ranges,
      only E. sakazakii could be lysised. The phage SK2 isolated from ATCC 51329 could
      form plaques on 24 of all 27 E. sakazakii strains (89%). All five phage particles
      had the hexagonal heads and tails after observing with negatively stained method
      by electron microscope. Random amplified polymorphic DNA analysis showed the
      polymorphism of the five phages. CONCLUSION: E. sakazakii phages isolated from
      sewage were only sensitive to E. sakazakii, and had potential usage in typing,
      preventing, treating E. sakazakii and entironment protection.

PMID- 19160821
TI  - [Observation of bacteria photodynamic inactivation induced by hematoporphvrin
      monomethyl ether by atomic force microscope].
AB  - OBJECTIVE: To study the photodynamic inactivation of Gram-positive bacteria
      Staphylococcus aureus and Gram-negative bacteria Escherichia coli by
      hematoporyrin monomethyl ether. METHODS: Bacteria incubated with different
      concentrations of hematoporyrin monomethyl ether (HMME) and then irradiated with
      visual light for 30minutes, bacteria inactivation efficiency was detected with
      the reduction of colony unit, and morphological changes were observed with atomic
      force microscope (AFM). RESULTS: Results indicated that 90% of Staphylococcus
      aureus was photoinactivated by illumination with visible light for 30 min (power
      density 200 mW/cm2) in the presence of 50 microg/mL HMME. The bacteria killing
      efficiency to Staphylococcus aureus with light irradiation was much obvious than
      that in dark at the same concentration of HMME, although without noticeable
      damage to E. coli with illumination or in dark. AFM ultrastructure images showed
      that the cells surface of photodynamic inactivated bacteria was all damaged
      seriously without the leakage of cell contents. CONCLUSION: We concluded that the
      attacked sites to bacteria cells by hematoporyrin monomethyl ether were bacteria
      membrane structure. Atomic force microscopy provides us a visual technique to
      study the mechanism of bacteria reacted with photosensitizers.

PMID- 19160822
TI  - [Recombinant phosphoenolpyruvate carboxykinase from Mycobacterium tuberculosis
      for sero diagnosis].
AB  - OBJECTIVE: To express phosphoenolpyruvate carboxykinase (PEPCK) of tuberculosis
      and evaluate its immune diagnostic ability. METHODS: PEPCK was cloned and
      expressed in prokaryotic expression system. We analyzed immune response of
      recombinant PEPCK with Western blot and studied the immunity of it through mice
      immunization. We also investigated the sensitivity and specificity of
      immunodiagnosis of PEPCK via detecting the sera from tubercular patients by using
      ELISA. The results were evaluated by comparing with a Mycobacterium tuberculosis
      antibody Colloidal Gold Diagnostic Kit. RESULTS: The recombinant protein was 72
      kDa and specifically reacted with anti-BCG antibody. Specific humoral immune
      response was elicited after mouse immunization with PEPCK protein and the high
      titer specific antibody was generated (1:1280). Antibodies were detected against
      M. tuberculosis 17.3% in all tuberculosis patients, 32.5% in patients harboring
      Mycobacterium currently and 12.9% in patients without M. tuberculosis. The
      sensitivity and specificity of ELISA were 51.0% and 96.7%. CONCLUSION: These
      results indicated that the recombinant PEPCK might be one of the suitable
      antigens for serodiagnosis of tuberculosis.

PMID- 19160823
TI  - [Purification and characterization of fibrinolytic enzyme from Bacillus subtilis
      BS-26].
AB  - OBJECTIVE: Thrombolytic therapy is a safe and effective treatment for thrombotic
      diseases. Microorganisms are possible sources of thrombolytic drugs. We purified
      and characterized fibrinolytic enzyme produced by Bacillus subtilis strain BS-26.
      METHODS: We examined the fibrinolytic enzyme activity by fibrin plate and
      purified fibrinolytic enzyme by ammonium sulfate fractional precipitation, anion
      exchange chromatography on DEAE-Sepharose Fast Flow and preparative PAGE.
      RESULTS: The fibrinolytic enzyme of the strain BS-26 was stable blow 50 degrees C
      and pH5.0-11.0, the optimal temperature was 42 degrees C and optimal pH was 9.0.
      Ca2+ and Mg2+ ions enhanced the fibrinolytic activity, whereas Cu2+ completely
      inhibited the enzyme. Phenylmethylsulfonyl fluoride (174.2 microg/mL), chicken
      ovomucoid (1000 microg/mL) and soybean trypsin inhibitor (1000 microg/mL) could
      inhibit enzyme activity, which indicated that the enzyme belonged to serine
      protease group. On plasminogen-free fibrin plates and plasminogen fibrin plates,
      the fibrinolytic activity had no obvious difference, indicating that the enzyme
      was a fibrinolytic enzyme which degraded fibrin directly, but not a plasminogen
      activator which degraded fibrin by activating plasminogen. A fibrinolytic enzyme
      was purified from the fermentation broth with recovery yield of 3.2%,
      purification factor of 41.0 fold and the specific activity 8750.0 U/mg. SDS-PAGE
      analysis of the purified protein showed only one band with molecular mass of 32
      kDa. CONCLUSION: A single fibrinolytic enzyme was purified, which provided the
      basis for large-scale production of fibrinolytic enzyme.

PMID- 19160824
TI  - [Association of phytoplasma with Bermuda grass white-leaf disease].
AB  - OBJECTIVE: Bermuda grass white leaf is an important disease on Bermuda grass all
      over the world. The aim of this research is to identify the pathogen which leads
      to Bermuda grass white leaf occurring on the Chinese mainland. METHODS: PCR
      amplification technique, sequence analysis and Southern hybridization were used.
      RESULTS: A 1.3 kb fragment was amplified by PCR phytoplasma universal primers and
      total DNA sample extracted from ill Bermuda grass as the amplified template.
      Sequence analysis of the amplified fragment indicated it clustered into
      Candidatus Phytoplasm Cynodontis. Southern hybridization analysis showed
      differential cingulums. CONCLUSION: The pathogen of Bermuda grass white leaf on
      the Chinese mainland contains phytoplasma, which provides a scientific basis for
      further identification, prevention and control of the disease.

PMID- 19160825
TI  - [Fermentation and polysaccharide antioxidative activity of a Libertella strain].
AB  - OBJECTIVE: To study fermentative production of exopolysaccharide (EPS) from a
      Libertella sp. and to evaluate its antioxidant activity. METHODS: We studied the
      effect of carbon source, nitrogen source, growth factors, pH and culture time on
      the production of Libertella exopolysaccharide. By determining the reduction
      capability, the decoloration of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the
      elimination of hydroxyl radicals, we evaluated the antioxidant activity of the
      Libertella exopolysaccharide. RESULTS: The optimum conditions for Libertella
      exopolysaccharide production were in a medium containing potato juice 20%,
      maltose 20 g/L, (NH4)2SO4 5 g/L and L-cystine 0.01 g/L and at pH 5.0 and 25
      degrees C fermented for 10 d. Under this condition, exopolysaccharide
      concentration in the fermentation broth reached 37.52 mg/L, 84.10% higher than
      that of the control. The scavenging effects of the Libertella exopolysaccharide
      on 1,1-diphenyl-2-picrylhydrazyl radical reached 14.21% with 20 mg/L
      exopolysaccharide, and the clearance rate of hydroxyl radicals reached 50.81%
      with 50 mg/L exopolysaccharide. CONCLUSION: The ferment conditions have
      significant influence on the production of Libertella exopolysaccharide. The
      exopolysaccharide showed obvious antioxidant activity.

PMID- 19160826
TI  - [Monitoring influenza A virus and Newcastle disease virus in migratory waterfowls
      in Sanjiang natural reserve of Heilongjiang Province].
AB  - OBJECTIVE: In order to monitor the present situation of Avian influenza virus
      (AIV) and Newcastle disease virus (NDV) in migratory waterfowls effectively, 158
      tracheal and cloacal swab samples for wild birds were collected from Sanjiang
      natural reserve during migratory seasons in October 2005, April 2006 and October
      2006. METHODS: Serial passages in specific pathogen free embryonated chicken
      eggs, haemagglutination activity (HA) text, hemagglutination inhibition (HI) text
      and RT-PCR detection were used to isolate and identify AIV and NDV. RESULTS:
      Twenty AIV isolates and 13 NDV isolates were collected in the test. Twenty AIV
      isolates were all from aquatic birds in October 2006, and among these isolates,
      12 AIV subtypes were identified definitely, 11 subtypes were found in mallards
      H2N2 (2/20), H2N6 (2/20), H3N4 (1/20), H3N6 (2/20), H3N7 (2/20), H3N8 (2/20),
      H6N2 (2/20), H11N2 (1/20), H11N3 (1/20), H11N5 (2/20), H11N6 (1/20), and 1
      subtype was found in garganey-H5N2 (1/20). Thirteen NDV isolates were collected
      in all three migratory seasons from 5 different species of waterfowls, including
      mallard (8/13), bean goose (1/13), white-fronted goose (1/13), common teal (1/13)
      and mandarin duck (2/13). CONCLUSION: The results indicated that mallard, which
      possesses huge population size and world wide distribution, could be considered
      one of the most important natural carrier of AIV and NDV and may have more
      important ecological significance on viruses transmission than other species of
      wild birds.

PMID- 19160827
TI  - [Beta-Proteorhizobia and nonrhizobial species--a review].
AB  - The terms alpha- and beta-rhizobia were proposed to distinguish the rhizobial
      alpha- and beta-Proteorhizobia respectively. In this review we present recently
      development of rhizobial taxonomy about beta-rhizobia in the genus Burkholeria,
      Cupriavidus isolated from Mimosa and alpha-Proteorhizobia belonging to
      Methylobacterium, Devosia, Ochrobactrum, Phyllobacterium and Blastobacter
      lineage. Furthermore, we also introduced the evolution of symbiosis related genes
      such as nodA and nifH, and posed some questions in detecting rhizobia. Finally,
      we discuss the prospects of research on rhizoiba in future.

PMID- 19160828
TI  - [Molecular determinants in regulating Pseudomonas aeruginosa type III secretion
      system--a review].
AB  - Pseudomonas aeruginosa is a Gram-negative opportunistic bacterial pathogen.
      Successful injection of virulence factors into host cells, evasion of
      phagocytosis and promotion of pathogenesis depend primarily on the function of
      type III secretion system (T3SS). A complex set of signaling pathways have been
      shown to modulate T3SS expression. In this review, a brief introduction is given
      on the composition, function, and molecular determinants that regulate P.
      aeruginosa T3SS gene expression.

PMID- 19160829
TI  - [Retinoic acid-inducible gene-I-like receptors and RNA virus recognition--a
      review].
AB  - Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) have recently been
      identified as cytoplasmic sensors for RNA viruses. The RLR signaling cascades
      induce the production of type I interferons and pro-inflammatory cytokines, which
      are rigorously regulated by the host. On other side, RNA viruses have evolved
      strategies to evade RLR signaling. In this review, we present our current
      understanding of RLR signaling in RNA virus recognition and antiviral innate
      immunity.

PMID- 19160830
TI  - [Research progresses of methanotrophs and methane monooxygenases].
AB  - Methanotrophs are a group of bacteria capable of utilizing methane as the sole
      carbon and energy source for their anabolism and catabolism. Since methanotrophs
      contain the unique enzymes of methane monooxygenases (MMOs), which can catalyze
      the oxidation of methane and short-chain alkanes and alkenes, they have potential
      applications in carbon recycle of nature and industrial biotechnology. Therefore,
      methanotrophs have been paid much more attention by the researchers in recent 20
      years. In this paper, the latest progresses in studies of methanotrophs and MMOs
      were reviewed, including taxonomy, function and distribution of methanotrophs,
      and structure, function and genetic engineering of MMOs. The future research
      directions of methanotrophs and MMOs as well as their applications were also
      discussed.

PMID- 19160831
TI  - [Expression of biologically active recombinant arresten in Nicotiana tabacum].
AB  - In this report, the biological activity of the recombinant Arresten expressed in
      Nicotiana tabacum was studied. The gene coding for the tumor angiogenesis
      inhibitor Arresten was PCR-amplified from the plasmid pCA and its plant
      expression vector named pCAMBIAarr was constructed by inserting the Arresten cDNA
      fragment into the NcoI/BstEII sites of the plant binary expression vector
      pCAMBIA1301. Then pCAMBIAarr was transferred into Agrobacterium tumefacien
      LBA4404 by the freeze-thaw method. The adventitious shoots and regenerated plants
      of Nicotiana tabacum with hygromycinB-resistance were obtained via Agrobacterium
      mediated leaf disk transformation method. Southern hybridization, RT-PCR and
      Western blotting analysis showed that the Arresten cDNA was integrated into the
      genome of some of the regenerated plants and the recombinant Arresten was
      expressed with a molecular size of 26 kD. Recombinant Arresten purified from
      transgenic tobacco leaves had an anti-proliferative effect on bovine endothelial
      cells. We speculate that biologically active recombinant Arresten can be produced
      by using plants as bioreactors.

PMID- 19160832
TI  - Change of hydrolase activity in germinating seeds of trxS transgenic barley.
AB  - Genetic modification of barley variety can be an efficient way to improve beer
      quality. The objective of this study was to understand the effect of trxS gene on
      hydrolases activities in transgenic and non-transgenic barley seeds. The results
      showed that alpha-amylase, free beta-amylase and limit dextrinase activity were
      increased in transgenic seeds in comparison with non-transgenic seeds. Sulfhydryl
      content of protein in transgenic seeds was also higher than that in non
      transgenic seeds, suggesting that trxS gene could express in barley seeds, which
      opens a new way for breeding new barley varieties to improve beer quality.

PMID- 19160833
TI  - [Identification of glucose-responsive elements in the promoter of UDP-L-rhamnose
      biosynthesis gene RHM1 in Arabidopsis thaliana].
AB  - In plants, UDP-L-rhamnose is one of the major components of cell wall skeleton.
      Rhamnose synthase plays a key role in rhamnose synthesis which converts UDP-D
      glucose into UDP-L-rhamnose in plants. In this study, we isolated the 1058 bp
      promoter region of the rhamnose synthase gene AtRHM1 from Arabidopsis genome by
      PCR, and created a series of deletions of AtRHM1 promoter ranging from -931 bp to
      +127 bp. The full length of the promoter and its deletion derivatives fused with
      GUS reporter gene were introduced into wild-type Arabidopsis by Agrobacterium
      mediated transformation respectively. The GUS staining and GUS enzymatic activity
      assay showed that the expression of AtRHM1 is induced at transcriptional level by
      glucose and the regulatory elements involved in the glucose response are located
      in the region of -931 bp - -752 bp which contains three G-box motifs.

PMID- 19160834
TI  - [A successive three-step 'Gap-repair' method to generate the mWAP-hLF hybrid gene
      locus].
AB  - To generate a mWAP-hLF hybrid locus that the transcription of human lactoferrin
      (hLF) genomic sequence is directed by the up & down stream regulatory sequence of
      murine whey acidic protein (mWAP) gene locus, we describe here a successive three
      step 'Gap-repair' method. First, a gap-repair vector based on pBR322 vector
      backbone by inserting six joint homologous arms was constructed. Then using 'Gap
      repair 'method mediated by Red recombination system of lambda-prophage in
      Escherichia coli, in the first step, the 8 kb 3' flanking region of the mWAP gene
      was subcloned from the Bacterial artificial chromosome which harbors the mWAP
      gene locus(mWAP BAC) into the gap-repair vector; in the second step, the 29 kb
      hLF genomic sequence from the ATG code to the TAA code was subcloned from the hLF
      BAC; in the third step, the 12 kb 5' flanking region of the mWAP gene was
      subcloned from the mWAP BAC. Finally, all these three DNA fragments were
      automatically combined together without any gap in the gap-repair vector, and a
      49 kb mWAP-hLF hybrid locus that the hLF genomic sequence was flanked by the 5' &
      3' flanking region of mWAP gene locus was constructed. The result was confirmed
      by PCR, restriction enzyme digestion and sequencing. Our method provide a new way
      for the construction of large mammary-gland expression vector.

PMID- 19160835
TI  - [Cloning, expression and purification of KDR tyrosine kinase].
AB  - The catalytic domain of KDR kinase (KDR-CD) was amplified from RNA of HUVCEs
      cells with RT-PCR and expressed in E. coli BL21(DE3) by plasmid pET30a as vector.
      The recombinant protein was purified with affinity chromatography (Ni-NTA).
      Western blotting showed that the recombinant KDR-CD was phosphorylated in E. coli
      BL21(DE3). The recombinant KDR-CD was identified to have kinase activity
      catalyzing the substrate phosphorylated with ATP in the enzymatic reaction.

PMID- 19160836
TI  - [Cloning, expressing and characterizing of a phosphoglycerate mutase gene of
      Schistosoma japonncum].
AB  - Phosphoglycerate mutase (PGAM) is a key enzyme in glycolytic pathways. With PCR
      technique based on an EST identified in our lab, a novel gene named SjPGAM
      (GenBank Accession No. EU374631) was cloned. Sequence analysis revealed that the
      ORF of SjPGAM gene contained 753 nucleotides, encoding 250 amino acids, and the
      molecular weight was about 28.26 kD. Real-time PCR analysis showed that the mRNA
      level of SjPGAM was much higher in the 14 days and 19 days schistosomula than
      other stages, suggesting that the gene was a schistosomula stage differential
      expression gene. The SjPGAM cDNA fragment was subcloned into an expression vector
      pET-28a (+) and transformed into Escherichia coli BL21 cells. In the presence of
      IPTG, the 31 kD fusion protein was expressed in included bodies. Western blotting
      revealed that the fusion protein could be recognized by the rabbit serum anti
      Schistosoma japonicum adult worm antigen preparation. The study provides
      important basis for investigating the mechanism of the PGAM in the glycolytic
      pathways of Schistosoma japonnicum.

PMID- 19160837
TI  - [Comparison of antiviral activity between FeIFN-omega and FeIFN-alpha].
AB  - Both IFN-omega and IFN-alpha belong to type I interferon and have antiviral,
      antiproliferative, immunomodulatory activities, but their bioactivities are
      usually different. FeIFN-omega gene was amplified by PCR. FeIFN-alpha gene was
      synthesized based on the published sequences of GenBank. Then the two types of
      feline interferon genes were subcloned into the pET-His vector, and expressed in
      Escherichia coli Rosetta (DE3). Recombinant interferons were purified by affinity
      chromatography with immobilized nickel chelating NTA (Ni-NTA) and their antiviral
      activity was estimated according to the ability of IFNs to inhibit the cytopathic
      effects (CPE) of virus on cells. Results showed that the antiviral activities
      against various viruses of FeIFN-omega were higher than those of FeIFN-alpha.
      Against H9N2 subtype avian influenza virus (AIV) and canine distemper virus
      (CDV), the antiviral activities of FeIFN-omega were 160 folds and 4 folds higher
      than those of FeIFN-alpha.

PMID- 19160838
TI  - [Cloning, expression and immunity of pilA gene and ompC gene from avian
      pathogenic Escherichia coli].
AB  - In order to amplify pilA gene and ompC gene of avian pathogenic Escherichia coli
      (APEC) strain, two pairs of primers were designed according to the GenBank
      sequences, and a 549 bp pilA gene and a 1104 bp ompC gene were obtained by PCR
      separately. Sequence analysis indicated that the homology of the nucleotide
      sequence of AEPC strain to those other reference strains was 98.18% of the pilA
      gene and 97.28% of the ompC gene. Two expression plasmids pETpilA and pETompC
      were constructed by inserting pilA gene and ompC gene into the prokaryotic
      expression vector pET-28a. The two plasmids were transformated into E. coli BL21
      separately and two recombinant strains BL21 (pETpilA) and BL21 (pETompC) were
      obtained. The type 1 fimbraie and the out membrane protein were highly expressed
      when the recombinant strain BL21 (pETpilA) and BL21 (pETompC) were induced by
      IPTG Two specific proteins were detected by SDS-PAGE and immunogenicity of the
      expressed protein was confirmed by Western blotting and ELISA. The expressed
      fimbraie and OmpC were transformed into vaccine. The protective immune response
      was proved after the mice were immunized with the two vaccines. The results
      showed that the recombinant strain BL21 (pETpilA) and BL21 (pETompC) could be as
      candidate vaccine to provide protective immune response against AEPC infection.

PMID- 19160839
TI  - [Construction of eukaryotic express vector of duck interleukin 18 gene and
      identification of bioactivity of its expressed protein].
AB  - Duck IL-18 gene was amplified from plasmid pGEM-DuIL-18 by PCR. The PCR product
      digested with Pst I and Xho I was inserted into eukaryotic express vector
      pcDNA3.1(+) to generate an recombinant expression plasmid pcDNA3.1/DuIL-18 (pDuIL
      18), and transformed into Escherichia coli JM109. The recombinant colonies were
      identified by restriction enzyme digestion, PCR and sequencing. DNA sequence
      confirmed the correct sequence of the recombinant eukaryotic expression plasmid
      pDuIL-18 in the reading frame and the ligation part. After the transfection of
      pDuIL-18 into Cos7 cells, duck IL-18 mRNA was expressed in Cos7 cell. The SDS
      PAGE analysis showed that the expressed duck IL-18 protein had molecular weight
      of 23 000 D. The results of methyl thiazolyl tetrazolium (MTT) assay showed that
      duck IL-18 protein expressed in Cos7 cell could induce significantly
      transformation of duck T lymphocytes. Immunoenhancement effect of recombinant
      expression plasmid pDuIL18 on avian influenza vaccine was observed by
      proliferation response of the T lymphocytes from spleen. It can obviously enhance
      the cell-mediated immune response.

PMID- 19160840
TI  - [Construction and application of chimeric infectious clones of porcine
      reproductive and respiratory syndrome virus].
AB  - In recent years, mass outbreaks of highly pathogenic (HP) porcine reproductive
      and respiratory syndrome virus (PRRSV) have spread all over the Chinese swine
      industry. Based on the first infectious cDNA clone of HP PRRSV strain pJX143 and
      that of an attenuated PRRSV, pAPRRS, constructed in our group, we constructed
      several chimeric clones with various substitutions of structural protein genes
      (ORF4-7) and 3' UTR between attenuated pAPRRS and virulent pJX143.Upon
      transfection of MA-104 cultured cells, all chimeric constructs pSX12, p5NX12, and
      p56N12 were rescued. The rescued viruses maintained the similar virological
      properties, based on the results of the growth curve of the rescued viruses. To
      test if the chimeric viruses can be used as a vaccine candidate, vSX12 and v56N12
      vaccinated pigs were challenged with the HP PRRSV JX143 strain. As a result, the
      vSX12 vaccinated pigs were all seroconverted by 14-day-post vaccination, while
      v56N12 vaccinated pigs showed poor antibody response. Upon challenge, the vSX12
      vaccinated group showed no signs of clinical PRRS syndrome, and virema period was
      shorten to 6 days post-challenge. Our results demonstrated that 1) vSX12 chimeric
      virus is a good vaccine candidate; 2) the virulence determinants of HP PRRSV
      probably located in coding regions other than ORF3-7 and 3' UTR, as our chimeric
      viruses were proved to be attenuated.

PMID- 19160841
TI  - [Differentiation of human amniotic fluid stem cells into cardiomyocytes through
      embryonic body formation].
AB  - To isolate human amniotic fluid stem cells (hASCs) and induce hASCs into
      cardiomyocytes after forming the embryonic bodies. We cultivated hASCs isolated
      from the amniotic fluid continually for over 42 passages. The biological
      characteristics of hASCs were detected by immunocytochemistry, RT-PCR and flow
      cytometer, hASCs at 10-15th passage were suspension cultured to form embryonic
      bodies that were induced to cardiomyocytes. Fibroblastoid-type hASCs were
      obtained. Immunocytochemistry, RT-PCR and flow cytometry analysis demonstrated
      that hASCs were positive for some specific makers of the embryonic stem cell.
      hASCs could form embryonic bodies that were alkaline-phosphatase positive and
      expressed fgf5, zeta-globin and alpha-fetoprotein. The embryonic bodies could
      differentiate into cardiomyocytes showing alpha-actin positive and Tbx5, Nkx2.5,
      GATA4 and alpha-MHC positive. We conclued that hASCs obtained from human amniotic
      fluid could differentiate into cardiomyocytes through the formation of embryonic
      bodies.

PMID- 19160842
TI  - [Hematopoietic repopulating ability of human CD34+ cells and CD34- cells in
      NOD/SCID mice].
AB  - The hematopoietic repopulating ability of fresh and cultured CD34+ cells and CD34
      cells derived from cord blood were compared by nonobese diabetic/severe combined
      immunodeficiency (NOD/SCID) mouse model. Fresh CD34+ cells and CD34- cells were
      isolated from fresh cord blood. Cultured CD34+ cells and CD34- cells were
      separated from cultured mononuclear cells (MNC). We transplanted these cells into
      sublethally irradiated NOD/SCID mice via the tail vein and sacrificed surviving
      mice after 6 weeks. The peripheral blood, spleen and bone marrow from each mouse
      were harvested for flow cytometry, colony-forming cells and human Alu sequences
      analyses. The proportions of CD45+ cells and human multilineage hematopoietic
      cells in NOD/SCID mice received CD34+ cells were close to that in the mice
      received both CD34+ cells and CD34- cells, while it was significantly higher than
      that in the mice received CD34- cells. Six weeks after transplantation, all the
      mice injected with cultured CD34- cells dead. The survival rate of mice injected
      with cultured CD34+ cells was 66.7%. All of the mice injected with both cultured
      CD34- and CD34+ cells survived. Moreover, CD45+ cells could be detected in all
      surviving mice, and human CD34, CD3, CD19, CD33 and CD71 antigen also could be
      detected on these CD45+ cells. The results showed that both fresh and cultured
      CD34+ cells had the capability of engraftment and hematopoiesis reconstitution,
      but CD34- cells hadn't the ability. However, CD34- cells had assistant effect on
      the hematopoietic repopulating ability of CD34+ cells.

PMID- 19160843
TI  - [Breeding of Actinobacillus succiniogenes mutants with improved succinate
      production based on metabolic flux analysis].
AB  - It is very important to obtain high yield mutant strains on the base of metabolic
      flux analysis of Actinobacillus succinogenes S.JST for the industrial
      bioconversion of succinic acid. The metabolic pathway was analized at first and
      the flux of the metabolic networks was calculated by matrix. In order to decrease
      acetic acid flux, the strains mutated by soft X-ray of synchronous radiation were
      screened on the plates with high concentration of fluoroacetic acid. For
      decreasing the metabolic flux of ethanol the site-directed mutagenesis was
      carried out for the reduction of alcohol dehydrogenase(Adh) specific activity.
      Then the enzyme activity determination and the gene sequence analysis of the
      mutant strain was compared with those of the parent strain. Metabolic flux
      analysis of the parent strain indicated that the flux of succinic acid was
      1.78(mmol/g/h) and that the flux of acetic acid and ethanol were 0.60 (mmol/g/h)
      and 1.04( mmol/g/h), respectively. Meanwhile the metabolic pathway analysis
      showed that the ethanol metabolism enhanced the lacking of H electron donor
      during the synthesis of succinic acid and that the succinic acid flux was
      weakened by the metabolism of byproducts ethanol and acetic acid. Compared with
      the parent strain, the acetic acid flux of anti-fluoroacetic mutant strain S.JST1
      was 0.024 (mmol/g/h), decreasing by 96%. Then the enzyme determination showed
      that the specific activity unit of phosphotransacetylase(Pta) decreased from 602
      to 74 and a mutated site was founded in the pta gene of the mutant strain S.JST1.
      Compared with that of the parent strain S.JST1 the ethanol flux of adh-site
      directed mutant strain S.JST2 was 0.020 (mmol/g/h), decreasing by 98%. Then the
      enzyme determination showed that the specific activity unit of Adh decreased from
      585 to 62 and the yield of end product succinic acid was 65.7 (g/L). The
      interdiction of Adh and Pta decreased the metabolism of byproducts and the H
      electron donor was well balanced, thus the succinic acid flux was strengthened by
      the redundant carbon flux from these byproducts. The mutant strain S.JST2
      obtained in this paper deserves being extended to application of industrial
      fermentation.

PMID- 19160844
TI  - [Influences of phosphate deficiency in the medium on growth, activities of
      antioxidant enzymes and utilization of nitrogen resource in Cucumis sativus hairy
      roots].
AB  - Effects of phosphorus deficiency in the medium on growth and morphology and
      activities of SOD and POD, utilization of nitrogen and calcium in the medium
      during liquid culture of Cucumis sativus hairy roots were investigated. The
      results showed that C. sativus hairy roots can not grow in the medium without
      addition of any phosphorus. When cultured into the medium with different Pi
      concentrations, the growth of C. sativus hairy roots was significantly inhibited
      with the decreasing of Pi concentration in the medium, its main roots became
      thinner and longer, the number of its lateral roots was decreased and its lateral
      roots became shorter and smaller. Compared to the medium with full strength
      phosphorus, the content of soluble proteins in C. sativus hairy roots cultured
      under Pi deficiency was significantly lower than that with standard full-length
      Pi, while POD and SOD activities in C. sativus hairy roots were significantly
      stimulated. Compared to the control (without addition of any phosphorus in the
      medium), the activities of POD and SOD in C. sativus hairy roots cultured in the
      medium with different concentration of Pi were lower than the control. When C.
      sativus hairy roots were cultured into medium with different Pi concentrations,
      the medium conductivity was gradually decreased with time and with direct
      proportion of the initial Pi concentration of the medium; NH4(+)-N and NO3(-)-N
      of the medium was gradually absorbed and utilized, at day 15, NH4(+)-N of the
      medium was nearly used up but its NO3(-)-N was not used up until cultured for 30
      days. Pi deficiency in the medium could decrease the consumption rate of NO3(-)-N
      and inhibited the absorption and utilization of calcium of the medium by C.
      sativus hairy roots. Proper enhancement of Pi concentration could stimulate
      absorption and consumption of calcium of the medium.

PMID- 19160845
TI  - [Effects of leptin on porcine primary adiocytes lipolysis and mRNA expression of
      key lipolytic enzymes].
AB  - Leptin, a cytokine predominantly secreted from fat tissue, plays an important
      role in regulating organism energy balance. Leptin can stimulate lipolysis, but
      the mechanism is unclear. In order to study the molecular mechanism of leptin
      stimulating lipolysis, we systemically studied the mRNA expression of key
      lipolytic enzymes. Morphological observation, Oil Red O staining and RT-PCR were
      used to identify pig primary adipocytes; commercial kits were used to measure the
      glycerol and FFA release; Semiquantitative RT-PCR was used to detect the mRNA
      expression of key lipolytic enzymes. The results showed that 100 nmol/L leptin up
      regulated the mRNA expression of ATGL, TGH-2, HSL, MGL and LPL (P<0.01), but down
      regulated the Perilipin mRNA expression (P<0.01). At the same time, leptin
      promoted the glycerol release in a dose dependent manner (P<0.01), but had no
      effect on the FFA release (P>0.05). These indicate that leptin may mainly
      stimulate lipolysis in pig primary adipocytes by up-regulating the expression of
      ATGL, MGL, LPL and down-regulating the expression of Perilipin. The unchanged FFA
      release may be resulted from Leptin promoting UCPs mRNA expression and increasing
      FFA expenditure.

PMID- 19160846
TI  - [Cloning of PTD-NPY fusion gene and its secretory expression in Pichia pastoris].
AB  - The PTD-NPY fusion gene derived from HIV-1 TAT protein transduction domain and
      rat neuropeptide Y was amplified by overlap extension PCR, digested and subcloned
      into yeast expression vector pPICZ alpha A to construct recombinant expression
      plasmid pPICZ alpha-PTD-NPY. The cloned PTD-NPY fusion gene was identified by PCR
      and restriction enzyme digestion and sequenced. The exact recombinant plasmid was
      linearized by Sac I and integrated by electrotransformation into the genome of
      Pichia pastoris GS115 cells. Then, these positive recombinant yeast cells were
      induced by 10 mL/L methanol to express soluble PTD-NPY fusion protein. After 120
      h of methanol induction, the SDS-PAGE electrophoresis result indicated PTD-NPY
      fusion protein was efficiently secreted into the medium. Western blotting
      analysis proved that the expressed fusion protein had specific NPY binding
      activity. The successful expression of PTD-NPY fusion protein in Pichia pastoris
      provided basis for its further application study.

PMID- 19160847
TI  - [Cloning, expression and antiviral activity of arctic fox (Alopex lagopus)
      interferon-gamma gene].
AB  - In order to characterize the biological activity of fox (Vulpes vulpes)
      interferon gamma(VuIFN-gamma), We have isolated the cDNA encoding arctic fox
      (Alopex lagopus) VuIFN-gamma. This cDNA encodes a 23 amino acid signal peptide
      and a 144 amino acid mature protein, which shares 99.8% or 99.4% for nucleotide
      identity with silver fox and canine, respectively, and 100% for amino acid
      identity. Expression of recombinant mature arctic fox interferon gamma (mVuIFN
      gamma) in bacterial system was confirmed by SDS-PAGE and Western blotting
      analysis. Recombinant VuIFN-gamma showed higher antiviral activity against
      vesicular stomatitis virus in cultured Vero and MDCK by inhibiting virus induced
      cytopathic effect, In view of the immunomodulatory and antiviral activities of
      VuIFN-gamma, it may provide a basis for further research on antiviral therapy of
      recombinant VuIFN-gamma in economic animal practice.

PMID- 19160848
TI  - [Relationship between structure and function of loops from Bacillus thuringiensis
      insecticidal crystal protein Cry1Ba].
AB  - To indicate the relationship between structure and function of loops from
      Bacillus thuringiensis insecticidal crystal protein Cry1Ba, and the influence of
      amino acids mutation on toxicity against diamond back moth Plutella xylostella,
      five mutations at the loops of Cry1Ba were constructed by overlapping primer PCR,
      and expressed in E. coli BL21 (DE3). Bioassay results showed that the toxicity of
      mutation M1 (loop1: 340WSNTR344-deletion), compared with that of Cry1Ba (LC50
      0.96 microg/mL), decreased significantly with LC50 35.51 microg/mL. And the
      toxicity of mutation M2 (402Y-G), M3 (400GIYLEP405-PSAV), M4 (400GIYLEPIH407
      ILGS) was also reduced to some extent respectively. Only M5 (mutation at loop3:
      472LQSRV476 - AGAVYTL) showed slightly increased activity against P. xylostella,
      but not significantly (LC50 0.81 microg/mL). Referring to the structures of
      Cry1Ba which was predicted using Swiss-Model software, and bioassay data, we can
      conclude that loop1 and loop2 play a important role on determining the activity
      of Cry1Ba against P. xylostella.

PMID- 19160849
TI  - [Effect of organic solvent on production of organic acids from municipal sludge].
AB  - Organic acids are important chemicals. Municipal sludge can be reused by
      anaerobic fermentation, from which organic acids could be obtained with liquid
      liquid extraction and useful substances be produced. Based on the determination
      of optimum organic solvent and extractant, it effect on production of volatile
      fatty acid (VFA) from municipal sludge was investigated in this research. The
      results showed that the proper organic solvent and extractant were sulfonated
      kerosene and trialkyl phosphine oxide. And, the VFA production was improved by a
      slight amount of sulfonated kerosene.

PMID- 19160850
TI  - [Relativity of gene expression and co-regulated gene patterns in feature KEGG
      pathways].
AB  - We revealed the feature pathways by computing the classification error rates of
      out-of-bag (OOB) by random forests combined with pathway analysis. At each
      feature pathway, the relativity of gene expression was studied and the co
      regulated gene patterns under different experiment conditions were analyzed by
      MAP (Mining attribute profile) algorithm. The discovered patterns were also
      clustered by the average-linkage hierarchical clustering technique. The results
      showed that the expression of genes at the same pathway was similar. The co
      regulated patterns were found in two feature pathways of which one contained 108
      patterns and the other contained 1 pattern. The results of clusters showed that
      the smallest Pearson coefficient of the clusters was more than 0.623, indicating
      that the co-regulated patterns in different experiment conditions were more
      similar at the same KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway. The
      methods can provide biological insight into the study of microarray data.

PMID- 19160851
TI  - [Expression and identification of PEBP-like gene from Saussurea involucrate
      Kar.er kir in Escherichia coli].
AB  - This assay was designed to construct the prokaryotic expression vector,
      investigate the expression of PEBP-like in Escherichia coli and purify its
      product. The PEBP gene was inserted into the vector pET30a (+). The recombinant
      vector was transferred into E. coli BL21 (DE3)and induced the expression of
      protein by low concentration of IPTG and low temperature overnight. After
      purification, the supernatants were analyzed by SDS-PAGE and the results were
      identified by Western blotting. After IPTG induction, a new anticipating fusion
      protein of 28 kD appeared as an expected size, and its product was 26.8% in total
      protein, the fusion protein was positive by Western blotting. The prokaryotic
      expression system of PEBP-like is successfully constructed. It lays the
      foundation for the further application study on the antifreeze characters of the
      PEBP.

PMID- 19160852
TI  - [Establishment of human IFN-gamma in vitro release assay and its application in
      tuberculosis diagnosis].
AB  - This study aimed to establish human IFN-gamma (hIFN-gamma) in vitro release assay
      and to apply it in diagnosis of human tuberculosis. Human IFN-gamma gene was
      cloned and expressed in Escherichia coli. The recombinant hIFN-gamma was purified
      and used as immunogen to immunize mice and rabbits respectively. Monoclonal and
      polyclonal antibodies were respectively developed and a sandwich ELISA was
      established. The heparized whole blood from 111 active tuberculosis patients and
      292 clinical healthy controls were collected. The blood was stimulated with
      tuberculosis specific fused antigen ESAT-6/CFP-10 and the plasma was collected
      for IFN-gamma detection. The sensitivity for tuberculosis diagnosis was 95.5%,
      whereas the positive detection rate for the healthy controls was 16.7%. There was
      a significant difference between the patients and healthy controls (P<0.01)
      indicating that this assay had a high sensitivity and specificity, and thus could
      be promising in tuberculosis diagnosis.

PMID- 19160853
TI  - [Interferon alpha-2b modified with polyethylene glycol].
AB  - In order to obtain a more stable PEGylated interferon alpha-2b, and prolong its
      half life, interferon alpha-2b (IFN alpha-2b) was modified with monomethoxy
      polyethylene glycol propionaldehyde (mPEG-ALD) 20000. It was found that the
      optimized reaction condition for the maximum bioactivity and highest PEGylation
      degree of the mono PEGylated interferon alpha-2b was as follows: in 20 mmol/L, pH
      6.5, citric acid and sodium dihydrogen phosphate buffer, the concentration of IFN
      alpha-2b was 4 mg/mL, and the molar ratio of PEG/IFN alpha-2b was 8:1, and the
      reaction time was 20 h at 4 degrees C. Under the optimized reaction condition,
      the mono PEGylation degree reached to 55%. Ion exchange chromatography was used
      to separate and purify mono PEGylated interferon alpha-2b from the reaction
      mixture. The purity of mono PEGylated interferon alpha-2b was higher than 97%
      characterized by HPLC. The bioactivity of the mono PEGylated interferon alpha-2b
      was 13.4% of the native IFN alpha-2b, while its half life in SD rat is much
      longer than the native IFN alpha-2b. The mono PEGylated interferon alpha-2b is
      also stable in aqueous.

PMID- 19160854
TI  - [Preparation of monoclonal antibodies against VP2 protein of Asia I type foot-and
      mouth disease virus and establishment of a competitive ELISA for the detection of
      antibodies].
AB  - Monoclonal antibodies against FMDV vp2 protein were prepared and a competitive
      ELISA based on the monoclonal antibodies and vp2 protein was established. Balb/c
      mice were immunized with Escherichia coli expressed fusion protein. The
      splenocytes from immunized mice were fused with myeloma cells SP2/0. The
      hybridism cells were screened by indirect ELISA and limited dilution method. Two
      hybndoma cell Iines secreting mAbs against Asia I type foot-and-mouth disease
      were obtained. The titer and relative affinity of mAbs were determined by ELISA.
      Specificity of mAbs was analyzed by Western blotting. The ELISA titers of the
      ascites induced by the two hybridism cells were above 100 x 2(9).A competitive
      ELISA for the use of FMDV antibody detection was established using E. coli
      expressed fusion protein as coating antigen and HRP-labled mAb as detecting
      antibody. Clinical tests showed the method had 89.0 percent agreement with UBI
      Kit to detection of FMDV antibodies and 86.5 percent agreement with LPB- ELISA
      kit (Ceditest kit) for detection of antibodies against Foot-and-Mouth Disease
      Virus respectively.

PMID- 19160855
TI  - [Isolation and cultivation of goat embryo stem cells].
AB  - Morulaes and blastocysts obtained from Guanzhong dairy goats 6-7 days after
      mating were treated with whole embryo cultivaton, enzymatic digestion and
      immunosurgery separately. The goat embryonic stem cells (ESC) were isolated and
      cultured on a feeder layer of mitomycin-inactivated mouse embryo fibroblasts
      (MEF). The characteristics of goat ESCs were analyzed by immunohistochemisty, RT
      PCR and inducing differentiation in vitro. The results indicated that the embryos
      were easier to attach the culture dish and form primary colonies with whole
      embryo method. There were colonies that maintained undifferentiated for 18
      passages. The ESCs expressed the protein of Nanog, Oct4 and SSEA-3, whereas the
      protein of SSEA-4 was absent and the protein of SSEA-1 was weakly expressed. In
      addition, the genes of Nanog, Oct4, TERT and CD117 were expressed in goat ESCs.
      The cells also could differentiate to myocardial cells when induced in vitro by
      DMSO. These results suggest that the goat ESCs have characteristics of ESCs.

PMID- 19160856
TI  - [Applied anatomy of operation through posterior tympanum approach].
AB  - OBJECTIVE: To provide the anatomic data for operation on the middle ear through
      the observation and measurement of related anatomic structure. METHOD: Forty
      human temporal bones of 20 voluntary bone donors were dissected, relative
      anatomical data of operation were observed and measured under operating
      microscope through posterior tympanum approach entering posterior tympanum.
      RESULT: The average distances from suprameatal spine to short crus of incus,
      pyramid segment of facial canal were 19.14 mm, 16.30 mm, respectively. The
      average distances from pyramid segment of facial canal to the surface of mastoid,
      crotch of chorda tympani nerve, posterior wall of auditory meatus were 20.84 mm,
      11.28 mm, 4.40 mm, respectively. The average length of facial nerve in the
      horizontal segment, the perpendicular paragraph was about 11.60 mm, 15.30 mm,
      respectively. The average distance from pyramidal eminence to the anterior lip of
      round window niche, from oval window to round window niche, from incudostapedial
      joint to round window niche was 4.46 mm, 3.74 mm, 3.80 mm, respectively. The
      included angle of facial nerve in the horizontal segment and chorda tympani nerve
      with facial nerve in the perpendicular paragraph was 110.4 degrees, 24.8 degrees,
      respectively. Horizontal semicircular canal and facial nerve in the level
      paragraph was 17.5 degrees, long process of incus and incus buttress was 46.0
      degrees. CONCLUSION: The position of anatomic structure in middle ear was
      constant and the relationship including distance and angle between anatomic
      structures changed in limited region. The anatomical parameters provide a
      reference value for avoiding the injury during the operation.

PMID- 19160858
TI  - [Expression and clinical significance of insulin like growth factor-1 protein in
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To evaluate the expression of IGF-1R protein and its clinical
      signification in nasopharyngeal carcinoma. METHOD: SP immunohistochemical
      staining was performed to detect the expression of IGF-1R in 63 cases of NPC and
      21 inflammatory nasopharyngeal mucosa; and the expression of IGF-1R in three NPC
      cell lines and chronic nasopharyngitis tissues was examined by western blots.
      RESULT: The positive rates of IGF-1R were 82.5% and 14.3% respectively in 63
      cases of NPC and 21 inflammatory nasopharyngeal mucosa; it also showed stronger
      positive expression in Stage III-IV of NPC than that in stage I-II (P < 0 01);
      IGF-1R positive expression in cases of NPC with cervical lymph node metastasis
      was significantly higher than that of NPC without lymph node metastasis (P <
      0.05); it more often appears in recurrent cases than in primary cases (P < 0.05);
      IGF-1R positive expression had a significantly stronger in patients whose
      survival time less than 5 years than that in patients whose survival time over 5
      years (P < 0.01). CONCLUSION: Over-expression of IGF-1R is related to poor
      differentiation of NPC, also may be linked with oncogenesis and development of
      NPC. The over-expression of IGF-1R may be one of a prognostic factors in NPC. The
      IGF-1R might be a potential therapeutic target in nasopharyngeal cancer.

PMID- 19160857
TI  - [A short term study on the efficacies of intratympanic prednisolone and
      dexamethasone injection for subjective tinnitus].
AB  - OBJECTIVE: To study the efficacies of intratympanic prednisolone and
      dexamethasone injection for the subjective tinnitus. METHOD: A prospective study
      was designed to compare the efficacies of intratympanic prednisolone injection,
      intratympanic dexamethasone injection and carbamazepine by oral administration
      for subjective tinnitus. Seventy-three cases (78 ears) with subjective tinnitus
      for more than one month and treated by conservative therapy (such as vasodilator
      agent, Vitamin B, etc. by oral intake. ) were involved. The patients were
      randomized into 3 groups. Thirty-four cases (35 ears) were included in
      prednisolone group, 18 cases (18 ears) in dexamethasone group with intratympanic
      injection of prednisolone or dexamethasone, and 21 cases (25 ears) in
      carbamazepine group as a control group with oral administration of carbamazepine.
      All of the cases in intratympanic perfusion group were injected twice in the
      first week, then once a week consecutively. The patients were acupunctured 4-5
      times in the whole course of treatment. All of the cases accepted Betahistine
      Mesylate, Mecobalamin and Vitamin B1 by oral intake at the same time. Pure tone
      audiogram and tinnitus matching were tested before the treatment immediately
      after the course of treatment, and were tested again after half a year's
      following up. RESULT: All of the cases accepted the whole treatment and were
      followed up for half a year successfully. The effective rate of the prednisolone
      group, dexamethasone group and the carbamazepine group was 48.6%, 33.3%, 44.0%,
      respectively; the control rate half a year after the treatment was 45.7%, 27.8%,
      36.0%, respectively. There was no statistically significant difference in the
      effective rate and control rate between intratympanic perfusion group and
      carbamazepine group. There is a statistically significant difference both in the
      effective rate and the control rate between the prednisolone group and the
      dexamethasone group. Prednisolone may be better than dexamethasone in
      intratympanic perfusion for subjective tinnitus. CONCLUSION: Intratympanic
      steroid injection has a positive effect on subjective tinnitus and may be
      considered to be an alternative treatment to subjective tinnitus.

PMID- 19160859
TI  - [Impedance between modiolus and different walls of scala tympani].
AB  - OBJECTIVE: To compare the impedance between the modiolus and the inner wall of
      scala tympani with that between the modiolus and the outer wall of scala tympani.
      METHOD: The impedances between the modiolus and the inner wall of scala tympani
      and the impedance between the modiolus and the outer wall of scala tympani were
      measured, calculated and compared under different stimulating rates 0.1, 1.0,
      10.0 kHz. RESULT: The impedance between the modiolus and the inner wall of scala
      tympani is less than that between the modiolus and the outer wall of scala
      tympani (P < 0.05). CONCLUSION: To effectively stimulate the residual neurons in
      the spiral ganglion, the electrodes should be kept close to the inner wall of
      scale tympani.

PMID- 19160860
TI  - [Sequence analysis of DFNB59 gene in a Chinese family with dominantly inherited
      auditory neuropathy].
AB  - OBJECTIVE: To investigate if the DFNB59 gene contributes to the hearing loss of a
      Chinese pedigree with dominantly inherited auditory neuropathy (AN). METHOD: Nine
      members in four generations of the family were selected for this study. Genomic
      DNA was isolated from the peripheral leukocytes of the patients using the pure
      gene DNA isolation kits. Firstly, the subjects DNA fragment was PCR amplified
      using specific primers corresponding to exon 2 and 4 of the DFNB59 gene. Each
      fragment was purified and subsequently analyzed by direct sequencing in an
      applied biosystems 3730 automated DNA sequencer. The whole coding sequence of
      DFNB59 gene of one family patient were then PCR amplified and submitted for
      sequence analysis as described above. The resultant sequence data were compared
      with the standard sequence to identify deafness-associated mutations. RESULT: PCR
      amplifications were successfully conducted in all the subjects. We failed to
      detect the presence either of mutations T54I and R183W in the exon 2 and exon 4
      that have been reported, or any other deafness-associated mutations in the whole
      DFNB59 gene, by sequence analysis. CONCLUSION: The DFNB59 gene seems not
      contribute to the pathogenesis of this Chinese AN family, which suggesting new
      gene(s) involvement.

PMID- 19160861
TI  - [Changes of distortion product otoacoustic emissions in the patients with iron
      deficient anaemia].
AB  - OBJECTIVE: To observe the changes of distortion product otoacoustic emissions
      (DPOAE) in the patients with iron deficient anaemia (IDA). METHOD: Sixty cases
      who were taken health physical examination at ZhaBei District Central Hospital
      were divided into two groups, the normal group (30 cases, 60 ears) and the IDA
      group (30 patients, 60 ears) depend on the results of examination of hemoglobin
      and serum ferritin. The changes of DPOAEs at 4 kHz were observed. RESULT: A
      statistically significant decrease of DPOAE threshold level compared with the
      normal controls was seen at 4 kHz in the patients with IDA. CONCLUSION: The
      decreased threshold level of DPOAE at 4 kHz in IDA patients should relate to
      sensorineural hearing loss directly.

PMID- 19160862
TI  - [Cochlear implant approach in children patients with sigmoid sinus
      antedisplacement].
AB  - OBJECTIVE: To summarize the operation approach and management during cochlear
      implant operation in children with sigmoid sinus antedisplacement. METHOD: Five
      hundred and thirty-eight profound hearing loss children were performed auditory
      and imagiological examinations before cochlear implant. We analyzed the location
      of the sigmoid sinus from the high resolution CT scan and then performed cochlear
      implant to all these patients. RESULT: In all these 538 cochlear implant
      children, 4 cases (0.74%) had significant sigmoid sinus antedisplacement which
      cause the operation more difficult, 64 cases (11.9%) had slight sigmoid sinus
      antedisplacement which did not impact the ordinary cochlear implant procedures.
      CONCLUSION: Significant sigmoid sinus antedisplacement that impact cochlear
      implant operative procedures were seldom happen in children. In 538 cochlear
      implant children of our center, 4 cases had significant sigmoid sinus
      antedisplacement that impact cochlear implant operative procedures, we
      successfully complete these 4 operation through removal of the incus and abrasive
      reduction the posterior wall of bony external acoustic meatus.

PMID- 19160863
TI  - [The significance of p63 expression in thyroid neoplasm].
AB  - OBJECTIVE: To explore the significance of p63 expression in thyroid carcinoma,
      thyroid papillary carcinoma, thyroid follicular carcinoma, squamous cell
      carcinoma and medullary thyroid carcinoma in order to find the possible causes of
      such thyroid-related diseases and if there is some kind of relation among them.
      METHOD: The expression of p63 was examined in 10 thyroid carcinomas, 20 thyroid
      papillary carcinomas, 4 thyroid follicular carcinomas, 2 squamous cell carcinomas
      and 2 medullary thyroid carcinomas using direct immunofluorescence. RESULT: It
      was shown that p63 expressed in all the thyroid-related diseases mentioned above.
      In squamous cell carcinoma, p63 has the highest expression and the expression of
      p63 in thyroid papillary carcinoma has no obvious relationship with the patients
      age, sex, the size and location of tumor and neoplasm metastasis. CONCLUSION: The
      p63 masculine stem cells in thyroid could be one of the causes of some thyroid
      papillary carcinomas and thyroid follicular carcinomas. Thyroid papillary
      carcinoma, thyroid follicular carcinoma and squamous cell carcinoma may have
      similar origins.

PMID- 19160865
TI  - [Treatment of traumatic pseudoaneurysm of head and neck (report of 4 cases)].
AB  - OBJECTIVE: To discuss the clinical features, diagnosis and treatment of traumatic
      pseudoaneurysm. METHOD: We report 4 unusual cases of traumatic Pseudoaneurysms of
      the artery of head and neck. The data of the 4 cases was analysed
      retrospectively. RESULT: Four patients were with history of trauma and traumatic
      pseudoaneurysm were diagnosed by CT and DSA. Two of them accepted interventional
      vascular therapy, the others accepted surgical operation. Both methods are safe
      and effective. CONCLUSION: Traumatic pseudoaneurysms of the artery of head and
      neck are rare but potentially lethal. The diagnosis is not difficult. The
      interventional treatment should be the first choice if possible, while the
      surgical approach is another choice. Doctors should try to repair the arterial
      wall, to keep the artery patency and to decrease the unnecessary complications.

PMID- 19160864
TI  - [The value of treadmill exercise test for patients with moderate obstructive
      sleep apnea-hypopnea syndrome].
AB  - OBJECTIVE: To determine the value of treadmill exercise test in predicting
      patients with moderate OSAHS treated by uvulopalatopharyngoplasty (UPPP) and tone
      base reduction or oral appliance. METHOD: Sixty-six patients were treated by UPPP
      and tone base reduction or oral appliance. The data including PSG (AHI, SaO2) and
      treadmill exercise test (METs) was analysed. RESULT: The success rate (percentage
      of patients with at least 50% reduction in AHI) of UPPP and tone base reduction
      was 86.7%, and 84.8% in oral appliance. The difference (AHI, SaO2, METs or the
      success rate) between the groups of postoperation or oral appliance was
      nonsignificant (P > 0.05). CONCLUSION: As to moderate OSAHS, the UPPP and tone
      base reduction or oral appliance may be one of the effective therapy. The data
      including PSG (AHI, SaO2) and METs may be very useful in predicting effectiveness
      of treatment to OSAHS.

PMID- 19160867
TI  - [The difference of mitochondrial DNA 4,834 bp deletion mutation in tissues of
      inner ear and kidney and skeletal muscle of rat].
AB  - OBJECTIVE: To explore the difference of mitochondrial DNA 4,834 bp deletion
      mutation in tissues of inner ear, kidney and skeletal muscle and to discuss the
      possible mechanism of this kind of mutation in doxorubicin induced mtDNA 4,834 bp
      deletion mutation rat model. METHOD: Twenty-eight Wistar rats were randomly
      divided into two groups, one was experimental group (18 rats), the other was the
      blank control group (10 rats). The rats of experimental group were treated with
      intraperitoneal injection doxorubicin (1 mg/kg) twice a week for 3 months. The
      blank controls received an equivalent volume of saline instead. The tissues of
      inner ear, kidney and skeletal muscle were harvested and the mitochondrial DNA
      4,834 bp deletion mutation was detected by nested-PCR (nested polymers chain
      reaction) technique. The product of PCR was sequenced directly. RESULT: Two rats
      of the experimental group and the blank group died during the experiment. The
      frequency of the mitochondrial DNA 4,834 bp deletion mutation of inner ear,
      kidney and skeletal muscle were 68.75% (11/16), 75.00% (12/16) and 100.00%
      (16/16) respectively. The difference of this kind of mutation between tissues of
      the inner ear and the skeletal muscle was statistic significance (P < 0.05).
      There were no significant difference between the inner ear tissue and the kidney
      tissue (P > 0.05). None of the rats of the blank control group carry this kind of
      mitochondrial DNA mutation. CONCLUSION: The mitochondrial DNA 4,834 bp deletion
      mutation could be induce by doxorubicin in rats, and a notable difference were
      found of the frequencies of this kind of mutation between tissues of the inner
      ear and the skeletal muscle. So it suggested that this kind of mitochondrial DNA
      common deletion mutation was tissue specific.

PMID- 19160866
TI  - [Expression change of Muscarinic receptor subunits in rat flocculus following
      unilateral labyrinthectomy].
AB  - OBJECTIVE: To observe the expression of Muscarinic receptor M1, M3, M5 subunits
      in rat flocculus following left unilateral labyrinthectomy (UL). METHOD: The RT
      PCR was used to observe the expression of Muscarinic receptor M1, M3, M5 subunits
      post-unilateral labyrinthectomy and investigate its effect on vestibular
      compensation. RESULT: Muscarinic receptor M1, M3, M5 subunits were induced
      decrease in both side flocculus after unilateral labyrinthectomy. The expression
      was the least in the 1 d flocculus of following UL. The expression is rising from
      the 3-7 d flocculus of following UL. No difference was observed in the 7 d and
      sham operation flocculus following UL. No difference was observed in the
      ipsilateral and contralateral flocculus at any group. CONCLUSION: Muscarinic
      receptor M1, M3, M5 subunits were induced decrease in the flocculus after
      unilateral labyrinthectomy. But the significance of the change of Muscarinic
      receptor M1, M3, M5 subunits in the vestibular compensation is still unknown.

PMID- 19160868
TI  - Taming an intangible--change.

PMID- 19160869
TI  - Exploring diabetic care deficiencies and adverse events in home healthcare.
AB  - Little information is available about the strength of the relationship between
      home healthcare practices and the potential adverse events the Centers for
      Medicare and Medicaid Services tracks through its uniform reporting system. We
      examined charts of patients who experienced a hyperglycemic or hypoglycemic
      emergent event to learn more about how home healthcare processes may contribute
      to an adverse event and to explore other factors that may contribute to a
      patient's health outcome. Implicit peer review, informed by an explicit review
      process, determined that 10% of the emergent care events were probably avoidable
      if home care had been optimal, 56% were potentially avoidable, and 34% were
      unavoidable.

PMID- 19160870
TI  - Daily goals checklist--a goal-directed method to eliminate nosocomial infection
      in the intensive care unit.
AB  - Patients in the intensive care unit (ICU) are usually very sick and have
      complicated, multisystem dysfunctions and often life-threatening medical
      conditions. Their management requires skilled, comprehensive, and organized
      medical care. The use of the "ventilator bundle," "sepsis bundle;" and other
      evidence-based initiatives often results in improved quality of care and
      reduction of complications in the ICU. However, in reality, multiple factors can
      make the practitioners in the ICU overlook some of these quality measures. The
      daily goals checklist presented here is a quality tool that incorporates several
      evidence-based quality parameters, and it is easy to use and cost-effective. Its
      implementation is likely to greatly improve the quality of care and reduce
      complications in ICUs.

PMID- 19160871
TI  - Quartile dashboards: translating large data sets into performance improvement
      priorities.
AB  - Quality professionals are the first to understand challenges of transforming data
      into meaningful information for frontline staff, operational managers, and
      governing bodies. To understand an individual facility, service, or patient care
      unit's comparative performance from within large data sets, prioritization and
      focused data presentation are needed. This article presents a methodology for
      translating data from large data sets into dashboards for setting performance
      improvement priorities, in a simple way that takes advantage of tools readily
      available and easily used by support staff. This methodology is illustrated with
      examples from a large nursing quality data set, the California Nursing Outcomes
      Coalition.

PMID- 19160872
TI  - Interview with a quality leader: Peter Buerhaus on workforce issues. Interview by
      Linda Harrington.

PMID- 19160873
TI  - Creating a safety culture through the application of reliability science.
AB  - The discussion of patient safety in delivering healthcare services is an
      important topic given the current state of the healthcare system. The current
      organizational cultures of many healthcare organizations do not support a culture
      of patient safety and do not employ a specific framework in delivering safe,
      reliable patient care. This article discusses the principles of reliability
      science and the use of these principles in creating a culture of patient safety.
      Recommendations are made for nursing involvement in creating a change in
      healthcare organization culture, and implementation steps are presented for nurse
      managers who are interested in applying the principles of reliability science to
      create a culture of patient safety on their units.

PMID- 19160874
TI  - Automating PowerPoint to expand healthcare education--a how-to guide.
AB  - Faced with the challenges of disseminating innovative healthcare practices to
      numerous clinics over a broad geographic region, we developed a cost-effective
      method of delivering in-service information using an automated multimedia show,
      in lieu of repeatedly deploying our limited staff to provide in-person
      presentations. This article details the hardware, software, and methods involved
      in producing this exportable product, which enabled us to maximize outreach
      education while working within the constraints of limited staffing, time, and
      fiscal resources.

PMID- 19160875
TI  - Improving prophylactic perioperative antibiotic utilization in a hospital system.
AB  - The Centers for Medicare and Medicaid Services and the Centers for Disease
      Control and Prevention launched the Surgical Infection Prevention Project in
      2002. The groups developed performance measures regarding perioperative
      antibiotic use to prevent surgical site infections. Other organizations have
      since adopted these measures. Spectrum Health, a not-for-profit health system in
      western Michigan with seven hospitals, more than 140 service sites, and a 565,000
      member health insurance plan, formed an interdisciplinary quality improvement
      team to meet a goal of 100% adherence at two of its acute care hospitals in the
      city of Grand Rapids. Eighteen months later, process shifts had been achieved,
      demonstrating that a comprehensive, interdisciplinary approach can result in
      consistent perioperative antibiotic utilization.

PMID- 19160876
TI  - Government oversight of patient safety.

PMID- 19160877
TI  - Use of quality outcomes in advertising and marketing.

PMID- 19160878
TI  - Caring together.

PMID- 19160879
TI  - Kidney failure stabilizes after an increase over 2 decades.
AB  - The level of proteinuria is one of the most important predictors for progressive
      renal function loss in kidney disease. Reduction of urinary protein levels by
      renin-angiotensin-system (RAS) inhibitors limits renal function decline in
      patients with non-diabetic and diabetic nephropathies to the point that remission
      of the disease and regression of renal lesions have been reported. The increasing
      use of these drugs is possibly at the basis of the stabilization of rates of new
      cases of kidney failure reported to the US Renal Data System after a 2-decade
      period of progressive increases. RAS inhibition, however, may not be effective to
      the same degree in all patients. For those patients who do not reach a complete
      remission of proteinuria, treatment procedures to implement renoprotection should
      include strict blood pressure control (and metabolic control in diabetics),
      lowering of blood lipids, and lifestyle modifications. Early intervention may be
      important to maximize renoprotection, especially in diabetics.

PMID- 19160880
TI  - How to prevent progression to end stage renal disease.
AB  - Chronic kidney disease (CKD) and end stage renal disease (ESRD) are severe
      medical conditions, increasing threats to human health and socio-economic burdens
      in industrialized countries. CKD is assessed by an estimation of the glomerular
      filtration rate (eGFR). ESRD is an indication for renal replacement therapy by
      either dialysis or kidney-transplantation. Major risk factors for CKD are
      arterial hypertension, hyperglycemia and hyperlipidemia. The multifactorial
      pathogenesis of CKD and ESRD offers various therapeutic interventions: treatment
      of the underlying disease, anti-hypertensive therapy, glycemic control and anti
      diabetic therapy, anti-proteinuric therapy, renoprotection, and life style
      management. Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II
      receptor blockers (ARB) lower the systemic blood-pressure, reduce proteinuria and
      may slow or even halt the deterioration of renal function. Alert glycemic control
      is important to avoid or protract diabetic nephropathy. Restricted protein
      intake, cessation of cigarette smoking and chronic analgesic-abuse may also
      prevent the progression of chronic nephropathy.

PMID- 19160881
TI  - Renal anaemia: recent developments and future directions for improved management.
AB  - The global burden of chronic kidney disease (CKD) and associated anaemia is
      substantial. With the increasing numbers of patients that are likely to be
      affected in the future, approaches are required to improve anaemia management
      without increasing the workload of renal units. Advocating early treatment may
      improve patient outcomes and nurses are in an ideal position to identify and
      manage anaemia at an early stage in patients with CKD. In addition, adopting a
      multidisciplinary approach, alongside nephrologists, diabetologists,
      cardiologists, social workers, nutritionists and pharmacists, may allow nurses to
      detect and treat anaemia earlier in patients with CKD. Maintaining awareness of
      factors associated with decreased erythropoiesis-stimulating agents (ESAs)
      efficacy (e.g. iron deficiency or poor nutritional status) is also important. To
      reduce the burden on healthcare providers, anaemia management could be simplified
      by extending the administration interval of ESAs. Recent studies have explored
      the clinical efficacy of administration of currently available agents at
      intervals of up to once monthly in highly selected, stable patients. The use of
      an ESA that can control anaemia while maintaining haemoglobin levels within
      guideline ranges with extended administration intervals in all patients without
      the need for additional screening or stepwise dose adjustments with attendant
      monitoring may help improve patient care while reducing the workload of
      healthcare providers.

PMID- 19160882
TI  - Educational information for patients and caregivers in paediatric kidney
      transplant.
AB  - The aim is to offer, via the use of a manual, information to the parents and
      kidney-transplanted children, which offers hope to all with advice and
      explanation of procedures, and in this way, to better inform the recipients. The
      guide offers information to kidney-transplanted children and their caregivers,
      with clear instructions, simple vocabularies and attractive drawings or
      illustrations. With this guide, children and youngsters learn measurements of
      self-care, know the details of diet, recognize their physical limits and are
      informed about their necessary medication in order that the medication can be
      taken with minimal side effects. The parents find information to take care of a
      child who is transplanted and so has a second opportunity to enjoy life. This
      permits high hopes that self-confidence and self-esteem will be built up from
      advice and better information about how to get the best treatment. The quality of
      life recovered by the children and family is the best reward that can be given to
      the anonymous donors, who through the transplant, offer a possible reality for
      those patients who benefit from the chance to live again.

PMID- 19160884
TI  - Hyperkalaemia and haemodialysis patients: eletrocardiographic changes.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) present hydro
      electrolytic alterations due to the lack of adequate regulation of the internal
      medium. Of these alterations hyperkalaemia is frequent and produce neuromuscular
      symptoms, electrocardiographic changes and arrhythmias. Literature affirms that
      patients with ESRD present less prominent hyperkalaemia-related
      electrocardiographic changes than those patients with normal renal function.
      OBJECTIVES: To evaluate electrocardiographic alterations related with potassium
      in our ESRD patients and to compare the obtained results with those previously
      reported. METHODS: Descriptive, cross-sectional and prospective study in hospital
      haemodialysis (HD) patients. Pre- and post-HD serum potassium and other
      electrolyte concentrations were measured, and simultaneous 12-lead
      electrocardiogram (ECG) obtained at the first session of the week. An expert
      evaluated all ECG's. RESULTS: 39 patients were included in the study, 58.9% were
      women and 41.1% men, with a mean age 67.35 years (24-89). Serum potassium pre-HD
      range was 2.8 to 7.4 mEq/l (mean 5.07 mEq/L), 29.4% of the sample presented
      levels > or = 5.5 mEq/l and the most frequent alteration in the ECG was high and
      peaked T waves in leads V2 to V4. In the hyperkalaemia cases, the mean elevation
      of T wave was 7 mm. In 2 hyperkalaemia patients there was no elevation of T wave:
      one T wave was negative (K+ = 6 mEq/L) and another one stayed normal (K+ = 5.6
      mEq/L). CONCLUSIONS: The ECG continues to be a good tool of early hyperkalaemia
      detection, contributing to estimating severity. Patients with ESRD present
      electrocardiographic alterations similar to the healthy population.

PMID- 19160883
TI  - Dialysis and the environment: comparing home and unit based haemodialysis.
AB  - Dialysis, with its high dependence upon technology, disposable products and
      transport requirements, presents an unusual perspective for environmental
      management. This study considers and compares the environmental aspects arising
      from the provision of haemodialysis (HD) in the hospital and home setting.
      Resource items were measured at two levels of aggregation--unit and individual
      patient. Unit level items applied to common resources used for HD and require
      apportioning appropriately with patient level items that could be attributable to
      individuals. The data was measured in standard units such as hours and number of
      treatments or apportioned appropriately. With equivalent emissions calculated as
      CO2 annually per patient for standard HD. The findings indicate that HD in the
      home offers a net reduction in CO2 emissions per patient annually compared to
      hospital based HD, and provides an overview of how healthcare provision and the
      use of resources can be measured, enabling refinement in environmental management
      plans.

PMID- 19160885
TI  - Hydroxyethylstarch solutions versus saline for the treatment of intradialytic
      hypotension.
AB  - BACKGROUND: It is unknown whether the colloid solutions hydroxyethylstarch (HES)
      6% and 10% are equally effective as compared to saline alone for the treatment of
      intradialytic hypotension. METHODS: 44 stable patients treated with chronic
      intermittent haemodialysis were divided in two equally sized groups (Group I and
      Group II). When symptomatic hypotension occurred, patients received 100 ml 0.9%
      NaCl in Group I and 100 ml HES 6% in Group II. In the second month of the study,
      patients in Group I received HES 6% and saline was given in Group II. In the
      third and fourth month this treatment schedule was repeated, but now HES 10%
      instead of HES 6% was given. RESULTS AND CONCLUSION: HES solutions of 6% and 10%
      and saline were equally effective for the reversal of the intradialytic
      hypotension, but patients receiving HES 10% had a significant lower incidence of
      recurrent hypotension.

PMID- 19160886
TI  - Educational needs for blood pressure control in chronic kidney disease.
AB  - Strict blood pressure control reduces the risk of adverse outcomes in chronic
      kidney disease but is difficult to achieve. To inform the design of an
      educational intervention for patients with chronic kidney disease and
      hypertension, we used focus groups to identify key patient issues, from both
      patient and healthcare professional perspectives. Framework methodology was used
      to analyse data and patient confusion emerged as the core concept. This was both
      an effect and, in some cases, a cause of the six key themes identified: lack of
      basic knowledge; conflicting advice; nature of diagnosis; changes in evidence
      based practice; views on patient empowerment and views on the patient-health
      professional relationship. Educational needs identified involved addressing
      confusion by increasing both knowledge and motivation. In people with chronic
      kidney disease, confusion can lead to a lack of motivation and negative views
      that need to be addressed through appropriate education and support.

PMID- 19160887
TI  - The challenges encountered during a collaborative research project.
AB  - Collaborative research in the clinical environment ensures that research
      questions are valued and relevant to health care professionals who are based in
      the clinical setting. This form of research is not without its difficulties and
      can present numerous challenges and conflicts. For successful collaboration,
      research teams need to invest a considerable amount of commitment and energy into
      team functioning and relationships. In addition, the team needs to work together
      through the pooling of resources, interests and talents. This includes the
      sharing of tasks that are time consuming and work intensive. Using the
      experiences gained from the pilot phase of a collaborative study this paper will
      offer solutions to a number of challenges that emerged from this study.

PMID- 19160888
TI  - Developing a competency framework for renal nurses.

PMID- 19160889
TI  - [The supplements of Nutricion Hospitalaria].

PMID- 19160890
TI  - [The Cancun Declaration: the Cancun International Declaration on the Right at the
      hospital].

PMID- 19160891
TI  - [Nutritional management of inflammatory bowel disease].
AB  - Patients with inflammatory bowel disease present higher risk for hyponutrition.
      For this reason, an adequate nutritional support is frequently needed. In these
      patients, enteral nutrition should be used unless there exist contraindications.
      Nutritional support as the primary therapy is no indicated in adults (since
      steroidal therapy has shown to be more effective) but in the case of intolerance
      or lack of response to medical treatment. By contrast, enteral nutrition is
      considered a first line therapy in children. There is no clear benefit with the
      use of specific formulas (modified fat, glutamine...), so that their routine use
      is not recommended. In spite of the great technical and scientific advances,
      there are still many fields in which knowledge should be broaden; some of them
      are pointed out in this publication.

PMID- 19160892
TI  - Nutritional recommendation alone does not change the obesity profile of health
      professionals.
AB  - OBJECTIVE: To evaluate the frequency of overweight and obesity in health
      professionals, before and after a single specialized dietary recommendation.
      METHODS: Anthropometric measures of 579 workers of a general hospital in the city
      of Sao Paulo, Brazil were taken. The weight (f), height (h) and waist
      circunference (wc) were interpreted according to the WHO and NCEP ATP III
      guidelines. Nutrition specialist provided dietary and behavioral recommendations.
      The entire sample underwent a new evaluation one year later. RESULTS: At the
      first evaluation, 79 employees presente WC > or = 102 cm (male) or WC > or = 88
      cm (female). The association between WC > or = 102 cm (men) or WC > or = 88 cm
      (women) and BMI > or = 30 kg/m2 was found in 12.8% (69 subjects). The BMI
      distribution per age group indicated that the increase in overweight and obesity
      was directly proportional to the age increase. Physical activities were not
      practiced by 75% of the subjects studied. A year later, the evaluation indicated
      lack of statistical differences regarding the BMI and waist circumference of the
      sample and only 2.8% started to practice a physical activity. CONCLUSION: Dietary
      recommendation alone failed to promote changes in the eating habits of health
      professionals who work at a general hospital or to encourage them to practice
      exercise.

PMID- 19160893
TI  - Home artificial nutrition in a sanitary area of Galicia (Spain): descriptive
      study and proposals for the future.
AB  - OBJECTIVES: Home artificial nutrition (HAN) is a technique in increasing use, but
      the available data about it is limited because record-keeping in most countries
      is voluntary. Our objective is to describe the characteristics of HAN in our
      setting and to design a future proposal that improves its coordination. SUBJECTS:
      Retrospective review of 237 clinical histories of the patients who began with HAN
      in 2006 in our unit. VARIABLES: epidemiological information, indications, type of
      HAN, duration, complications and costs. RESULTS: Mean age: 75.4 years.
      Neurological and neoplasic diseases were the most frequent diagnoses (39.7% and
      32.1%, respectively). Main indications were: reduction of ingestion (41.8%) and
      neurological dysphagia (27.8%). 48.1% presented an important functional
      impairment and 63.7% needed a caregiver. HAN duration was < 3 months in 43.9% and
      the principal cause of suspension was the lack of follow-up. Oral nutrition was
      the preferred route (70.9%), gastrostomy was found in only 3.4%. High-energy
      formulas were mostly used in patients with supplements (53.3%) and standard
      formulas in those with complete diets (32.4%). Complications related to this
      therapy were low, mainly in the oral route. The most frequent were
      gastrointestinal (19.3%). Mean monthly cost: 159.3 euros/patient and an average
      travel distance of 26 km to pick up supplies. CONCLUSION: HAN is a safe, short
      term therapy, indicated in patients with diminished ingestion due to an acute
      situation. Our future proposal tries to improve the selection of patients, to
      facilitate the provision of materials and to customize follow-up to patient
      needs.

PMID- 19160894
TI  - Effect of non-steroidal anti-inflammatory drugs and the pro-carcinogen 1,2
      dimethylhydrazine on the rat intestinal membrane structure and function.
AB  - The present study was designed to evaluate the effects of three non-steroidal
      anti-inflammatory drugs (NSAIDs) with varying cycloxygenase selectivities on the
      small intestinal biochemical composition, function and histology during 1, 2
      dimethylhydrazine (DMH) administration. Sprague Dawley male rats were divided
      into five different groups viz: Group 1 (control, vehicle treated), Group 2 (DMH
      treated, 30 mg/kg body weight/week in 1 mM EDTA-saline, subcutaneously), Group 3
      (DMH + aspirin-60 mg/kg body weight), Group 4 (DMH + celecoxib-6 mg/kg body
      weight), Group 5 (DMH + etoricoxib-0.64 mg/kg body weight). After six weeks of
      treatment, brush border membrane was isolated from the jejunum segment of all the
      groups and changes in the associated enzymes such as sucrase, lactase, maltase,
      alkaline phosphatase, membrane lipid composition, fluorescence polarizations of
      diphenylhexatriene, pyrene excimer formation, histological changes and surface
      characteristics were studied. The results indicated a significant alteration in
      the enzyme activity as well as changes in the structure and function of the
      intestine in the presence of the pro-carcinogen, DMH, which suggests the possible
      chemopreventive efficacy of NSAIDs against the intestinal cancer.

PMID- 19160895
TI  - [Evolution of the blood parameters after morbid obesity surgery with the duodenal
      crossing technique].
AB  - OBJECTIVE: To assess the course of blood parameters from patients with morbid
      obesity submitted to the duodenal crossing surgical technique. METHODS: 110
      patients were studied in whom post-surgical monitoring of ponderal and laboratory
      parameters (the ones most influenced by this type of surgery such as hematocrit,
      hemoglobin, glucose, total proteins, albumin, calcium, PTH, ALT, Quick's index,
      total bilirubin, cholesterol and triglycerides, iron, ferritin, folic acid, and
      vitamin B12) has been carried out. Postsurgical monitoring has been carried out
      at months 3, 6, 12,18, 24, 36, 48, and 60. The shortest followup time has been
      one year. RESULTS: Weight loss is higher than 50% of the weight in excess and is
      maintained throughout the study, comprising more than 75% of the patients. During
      the postsurgical follow-up, there is a clear iron deficiency concurrent with the
      presence of anemia, as well as an evident increase in PTH. Normalization of
      glycemia, cholesterol, and triglyceride levels reaches almost 100%. CONCLUSIONS:
      changes in blood parameters presented by patients with morbid obesity submitted
      to the duodenal crossing technique, indicators of nutritional complications,
      affect about 10% of the patients (with the exception of iron deficiency and PTH
      impairment), and most of them are easily corrected with pharmacological and
      nutritional supplements, the body getting adapted to these deficits, without any
      severe clinical-biological impairment and with a trend towards normalization.

PMID- 19160896
TI  - [Nutritional risk evaluation and establishment of nutritional support in oncology
      patients according to the protocol of the Spanish Nutrition and Cancer Group].
AB  - INTRODUCTION: Cancer and its oncological treatment cause symptoms which increase
      the patients risk to suffer from malnutrition. This affects the patients health
      status negatively by increasing the number of complications, reducing the
      tolerance to the oncology treatment and a decrease of the patients quality of
      life. Motivated by this, a group of health professionals from several spanish
      regions met with the backing of the Sociedad Espanola de Nutricion Basica y
      Aplicada (SENBA) to address strategies to improve the quality of nutritional
      intervention in cancer patients. METHODS: This multidisciplinary group developed
      a protocol describing nutritional assessment and intervention in form of
      algorithms based on literature and personal experience. The patients are
      classified in a three step process: 1. type of their oncology treatment (curative
      or palliative); 2. nutritional risk of the antineoplastic therapy (low, medium or
      high risk) and 3. depending on the Subjective Global Assessment patient-generated
      (SGA-pg). The patients are classified as: A. patients with adequate nutritional
      state, B. patients with malnutrition or risk of malnutrition and C. patients
      suffering from severe malnutrition. During one year, the protocol has been used
      for 226 randomly chosen female and male patients older than 18 years. They were
      treated by the Medical and Radiotherapy Oncology outpatient clinic. RESULTS: More
      than a half of the patients were suffering from malnutrition (64%) increasing up
      to 81% for patients undergoing palliative treatment. Most of them were treated
      curatively (83%) and received oncology treatment with moderate or high
      nutritional risk (69%). 68% of patients were affected by some feeding difficulty.
      The mean percentage of weight loss has been 6.64% +/- 0.87 (min 0%, max 33%).
      Albumin values of 32% of the patients were between 3 and 3.5 g/dl and negatively
      correlated with feeding difficulties (p = 0.001). The body mass index (BMI) has
      not found to be a significant parameter for detecting malnutrition (only in 10%
      of the patients, the value was below 19.9 kg/m2). But a significant linear
      tendency when compared to feeding problems could be shown, such that in patients
      with less feeding problems a higher BMI has been found (p = 0.001). More than a
      half of the patients required nutritional counselling to control symptoms which
      made food intake difficult. One third of the patients needed oral nutritional
      supplementation. Following the nutritional intervention the weight of about 60%
      of the patients could be maintained and of one sixth it could be increased.
      CONCLUSION: The application of this protocol is useful, easy and could help
      detecting malnutrition in oncology patients. It provides the possibility to
      select those patients who can benefit from a specific nutritional intervention.
      If possible, the application of the protocol should be started immediatly after
      cancer is diagnosed. Nutritional support proves efficient for most of the
      patients.

PMID- 19160897
TI  - [Bibliometric study of the Journal Nutricion Hospitalaria for the period 2001
      2005: Part 1, Analysis of the scientific production].
AB  - OBJECTIVE: To assess the scientific activity and information production of the
      journal Nutricion Hospitalaria, for the period 2001-2005 by means of a
      Bibliometric study. METHOD: Cross-sectional descriptive study of the results
      obtained from the analysis of the articles published in the journal Nutricion
      Hospitalaria. The data were obtained by consulting the electronic version through
      the Web. In those cases in which there was a link breakdown, and thus, the
      inability to have access to the electronic document the printed version was
      consulted. All the documental possibilities were taken into account with the
      exception of communications to congresses. RESULTS: A total of 345 articles were
      published, 187 (54.20%) being original articles. The geographical distribution of
      the first author was Spanish in 287 articles (83.19%) and Latin American in 27
      (7.83%). Most of the articles are from health care centers (172 articles
      (49.86%)), and the cooperation index being 4.15. Madrid is the most productive
      province, for both the absolute and adjusted frequencies. The median number of
      references per article is 18, the mean being 23.52 (95% CI 20.93 - 26.10). The
      predominant language was Spanish, with 308 articles (89.28%). CONCLUSION:
      Nutricion Hospitalaria may be considered as a reference journal regarding
      information and scientific communication on Nutrition for both the Spanish and
      Latin American communities. The bibliometric parameters studied compare with
      those verified for the remaining top of the list Spanish scientific journals on
      health sciences.

PMID- 19160898
TI  - [Self-perception of cancer patients on the relationship existing between their
      nutritional status, their feeding status, and their illness].
AB  - INTRODUCTION: Knowing the opinion of oncologic patients about the importance they
      give to their feeding, the difficulties they have with feeding, their body image,
      weight, and ponderal changes, the relationship between their feeding and their
      illness, the relationship between their physical activity and their mood and
      health is essential to look for nutritional therapeutic interventions leading to
      improvement of quality of life and, in general, the feeling of well being. Thus,
      it is paramount to know the patients' opinion of these issues. MATERIAL AND
      METHODS: We passed a questionnaire to 131 patients. The patients were recruited
      from the Day-Hospital of the Medical Oncology and Radiotherapeutic Oncology
      Departments, and from the Hospitalization Department of Medical Oncology. In the
      questionnaire, we asked in a simple manner about the importance the patients give
      to all these issues. This is a 20-item questionnaire, divided into six parts: 1.
      Vital statistics; 2) perception about the disease and its relationship with
      feeding; 3) Perception of the relationship between physical activity and mood
      with feeding; 4) Nutritional therapies prescribed to the patients and their
      perception on its effect on the disease progression; 5) Current difficulties with
      feeding; 6) Demand of nutritional care. RESULTS: The patients mean age was 57 +/-
      13 years. 45% were males, and the remaining females. 81% life in an urban area,
      and only 14% in a rural area. The educational level was categorized in 5 groups:
      without education, basic education, elementary school, high school, or college
      studies. 28% had basic education, and 19% college studies, and only 8% had no
      education at all. Their occupation was also categorized in five groups: home
      keeping, student, unemployed, employed, and retired. 33% were employed, 29%
      retired, and 34% were home-keepers. Most of the patients (74%) are aware of their
      illness and perceive it as severe or very much severe. Most of these patients
      worry about their body image, weight, and ponderal changes, and they relate them
      with their feeding status. 74% find a relationship between their nutritional
      status and their physical activity, and 73% relate it with their mood. At least
      half of the patients perceive their mood as being low. Although 47% manifested
      having some difficulty for feeding, only 34% had received some information about
      their diet, 26% had consumed nutritional supplements, and 81% still consumed
      their diet without any change. The most common difficulties for feeding were
      decreased appetite (38%), early satiety (32%), and nausea (20%). The nutritional
      intervention most commonly required by the patients was general and specific
      nutritional education to alleviate the symptoms associated to oncologic
      therapies. CONCLUSIONS: Most of the patients are aware of the severity of their
      illness and care about their body image, weight, and ponderal changes, which they
      associate with their nutrition. Most of the patients find a close relationship
      between their nutritional status, their physical activity and their mood. More
      than half of the patients manifest having some difficulty feeding, but only one
      third of the population has received information about their diet some time. It
      is clearly shown that oncologic patients need different effective nutritional
      intervention measures contributing to improve their feeling of well being.

PMID- 19160899
TI  - Body mass index values for newborns according to gestational age.
AB  - OBJECTIVE: The combination of twho anthropometric parameters has been more
      appropriate to assess body composition and proportions in children, with special
      attention to the Body Mass Index (BMI), as it relates weight and length. However
      the BMI values for the neonatal period have not been determined yet. This study
      shows the BMI for newborns at different gestational ages represented in a normal
      smoothed percentile curve. METHODS: Retrospective study including 2,406
      appropriate for gestational age newborns following the Alexander et al curve
      (1996) from 29 to 42 weeks of gestational age. Weight and lenght were measured
      following standard procedures. For the construction a of a normal smoothed
      percentile curve, the 3rd, 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles
      were determined and a statistical procedure based on the mathematical model
      "sinosuoidal fit" was applied to establish a curve that estimates biological
      growth parameters. RESULTS: The Body Mass Index values for gestational age in all
      percentiles shows a steady increase up to 38 weeks, levels off up to the 40th
      week, followed by a slight decrease to the 42nd week in both genders. CONCLUSION:
      The results show a direct correlation between gestational age and Body Mass Index
      for both genders in the nine percentiles, and can provide a useful reference to
      assess intra-uterine proportional growth.

PMID- 19160900
TI  - [Nutritional control in orthopedic surgery patients].
AB  - OBJECTIVE: To assess the nutritional status of orthopaedic patients. DESIGN:
      Prospective observation study. SETTING: Tertiary hospital, Clinical Nutrition
      Unit. PATIENTS: 107 patients (56.1% women, 43.9% men, 62.1 +/- 20.4 years) are
      studied at admission to the orthopaedic unit and it is observed the evolution of
      orthopaedic surgery patients with hip or knee prosthesis. MATERIAL AND METHODS:
      Medical history, anthropometric data and three nutritional screening tools were
      considered: Mini-Nutritional Assessment (MNA), Malnutrition Universal Screening
      Tool (MUST) y Valoracion Global Subjetiva (VGS). It was assessed the prevalence
      of malnutrition in patients on admission to hospital, using different methods and
      determining if a correlation exists between malnutrition and other factors, such
      as the development of pressure sores of the dependence in activities of daily
      living. RESULTS: The risk of malnutrition is 22 and 24/100 patients admitted at
      hospital, if MNA and SGA are used, respectively (SGA caregorized 4% of the group
      as "malnourished"). 80% patients are considered to be at high risk of
      malnutrition using MUST. 1.7% patients presented a Body Mass Index (BMI) lower
      than 18.5. There is a strong agreement between malnutrition and neropsychological
      status (p = 0.001), and the dependence in activities of daily living (p = 0.002),
      and between medium and high risk of malnutrition and the development of pressure
      sores (p = 0.003). If MNA and SGA (p = 0.000) are used, post-surgical patients
      presents a deteriorating nutritional status. CONCLUSIONS: The prevalence of
      malnutrition in patients on admission to hospital is elevated. Orthopaedic
      surgery patients with hip and knee prosthesis presented a deteriorating
      nutritional status, and a higher incidence of pressure sores in a month.

PMID- 19160901
TI  - Factors associated with nosocomial diarrhea in patients with enteral tube
      feeding.
AB  - OBJECTIVES: Diarrhea is a frequent complication associated to enteral tube
      feeding (ETF) and it is a frequent cause of reduction or suspension of this type
      of nutritional support. Our objective was to evaluate the factors associated with
      nosocomial diarrhea in patients receiving ETF. RESULTS: The only significant
      factor associated with the appearance of diarrhea was antibiotic consumption,
      specially those patients receiving the combination of two or more antibiotics. We
      did not find any association between factors related to ETF, analytical
      parameters, nor other medications and diarrhea. CONCLUSIONS: Our observational
      data supports the idea that ETF should not be seen as a primary cause of
      diarrhea, other possible causes should be considered before reducing or
      discontinuing ETF administration.

PMID- 19160902
TI  - [Nutritional score risk for mortality in critically ill patients (NSRR:
      Nutritional Score Risk Research)].
AB  - AIM: The aim of our study has been applying a nutritional score risk to mortality
      in a group of patients who are in the Intensive Care Unit with or without
      previous disease. SETTING:  PATIENTS AND INTERVENTIONS: a prospective randomized
      study is designed. PLACE: At the intensive care units. PATIENTS: 228 admitted
      patients since april 2004 to december 2006 were included. The surveys were filled
      by the near relative who lived with the patient and/or ignorance of its pattern
      of food ingestion during the newspaper the survey was discarded. Critically ill
      patients were selected at random with pathologies (neurocritical, sepsis, trauma,
      patients, obstetrics critics, etc.) in 2 units of adult intensive cares.
      INTERVENTIONS: Dialogue with the families. VARIABLES: The selected nutritional
      score (NSR) which is elaborated for greater patients of 65 years now is modified
      to be used in intensive care unit, it is a questionnaire that can be very useful
      in the detection of initial nutritional risk of the critically ill patients.
      RESULTS: Our study demonstrated that the alterations of the NSR can be observed
      in all ages, established by not having a direct correlation between the age and
      the found NSR (r = 0.15, p = 0.018). This supports the concept of use of the NSR
      in the adult ages that are admitted in the intensive care unit. In addition, was
      found that suffering chronic diseases that alter the conditions of ingestion if
      would feed suitable is an isolated parameter significant to increase the death
      probability if the patient is in the ICU (p = 0.002). CONCLUSION: Patients with a
      high NSR at admittion to the intensive care unit for acute pathology are under
      risk to mortality by nutritional risk.

PMID- 19160903
TI  - [The megacystis-microcolon-intestinal hypoperistalsis syndrome: apropos of a case
      with prolonged survival].
AB  - Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a severe
      congenital disease with autosomal recessive inheritance, characterized by vesical
      distension and intestinal hypoperistalsis what causes intestinal obstruction in
      newborn, with other abnormalities associated. It presents a low incidence, about
      a hundred cases are reported in the bibliography. Life expectancy doesn't reach a
      year because of the sepsis failure generally. In our study the survival is higher
      than the majority of the cases reported, with good cuality of life and acceptable
      ponderal development. Home parenteral nutrition with the following and
      multidisciplinary collaboration in a strict way, establish the success' key in
      this pathology.

PMID- 19160904
TI  - [Hyponutrition: a severe underestimated surgical problem].

PMID- 19160905
TI  - Occupant restraint preferences of individuals traveling in motor vehicles while
      seated in their wheelchairs.
AB  - A survey among 127 wheelchair users was conducted to characterize wheelchair
      occupant restraint usage patterns, restraint deficiencies, user characteristics,
      and essential wheelchair occupant restraint design parameters for when
      individuals travel in motor vehicles while seated in their wheelchairs. Survey
      respondents value independent travel and seem generally interested in the use of
      an occupant restraint system that is attached to the wheelchair frame and that
      can be used independently by the wheelchair user without caregiver or vehicle
      driver assistance. Results of the survey further indicate that despite the
      relatively high percentage of respondents who are attempting to travel safely
      (78.8%), almost half of these wheelchair users have experienced injury or
      compromised wheelchair balance while traveling in motor vehicles.

PMID- 19160906
TI  - Disparities in usage of assistive technology among people with disabilities.
AB  - Assistive technology is essential to the lives of many people with disabilities,
      but disparities in usage put certain segments of the disability population at a
      particular disadvantage. This article uses survey data and statistical modeling
      to explore differences in technology usage across disability subpopulations.
      Responses to a 2005 survey of nearly 2,000 adult consumers of California
      Independent Living Centers reveal large differences in technology usage by age,
      race, ethnicity, education, income, and type and severity of disability.
      Statistical modeling of overall device usage, number of devices used, and usage
      of high-, medium-, and low-tech devices reveals several factors that appear to
      put people with disabilities at a disadvantage in accessing and using assistive
      devices. These factors include lower educational attainment, racial or ethnic
      minority status, lower household income, later disability onset, and disability
      related to mental as opposed to physical or sensory functioning. Findings
      highlight approaches needed to expand usage of and to promote equal access to
      technologies that enable greater social and economic participation for people
      with disabilities.

PMID- 19160907
TI  - A review of emerging access technologies for individuals with severe motor
      impairments.
AB  - Research and development in the field of access technologies for individuals with
      severe motor impairments has accelerated over the past 10 years. Many emergent
      alternatives to conventional mechanical switches, such as infrared sensing,
      electromyography, oculography, and computer vision, have been investigated for
      those retaining some limited volitional motor ability. At the same time,
      electroencephalography, electrocorticography, intracortical recordings, and
      electrodermal activity have been explored for those presenting as locked in. The
      relevant literature is scattered across many disciplines, obfuscating the
      strength of the clinical evidence in support of the different access technologies
      currently in development. This article systematically organizes the literature on
      the aforementioned access technologies, summarizing their underlying operational
      mechanisms while reviewing the clinical evidence reported between 1996 and 2006.
      Research evidence within this period is generally found to be at the case study
      or uncontrolled study level, with very modest sample sizes. Novel mechanical
      switches and electroencephalography-based access systems dominate the literature,
      whereas many other movement-based access modalities have emerged with promising
      early findings. Access methods for those without extant physical movement
      constitute a critical direction for future and ongoing research efforts.

PMID- 19160908
TI  - Transportation safety standards for wheelchair users: a review of voluntary
      standards for improved safety, usability, and independence of wheelchair-seated
      travelers.
AB  - Safe transportation for wheelchair users who do not transfer to the vehicle seat
      when traveling in motor vehicles requires after-market wheelchair tiedown and
      occupant restraint systems (WTORS) to secure the wheelchair and provide
      crashworthy restraint for the wheelchair-seated occupant. In the absence of
      adequate government safety standards, voluntary standards for the design and
      performance of WTORS, and for wheelchairs used as seats in motor vehicles, have
      been developed. The initial versions of these standards qualify equipment for use
      in all types and sizes of motor vehicles using a 30-mph (48-kph), 20-g frontal
      sled-impact test. The wheelchair standard requires four accessible, crash-tested
      securement points on wheelchairs so they can be more easily and effectively
      secured using a four-point strap-type tie-down system. Future voluntary standards
      are aimed at reducing injury risk for wheelchair-seated occupants in rear impacts
      and at providing a method for evaluating the crashworthiness of wheelchair
      seating systems independent of wheelchair base-frames. They also address improved
      usability and independence for wheelchair-seated travelers using public
      transportation by specifying universal docking interface geometry for wheelchairs
      and design and performance requirements for rear-facing wheelchair passenger
      stations for use in the very low-g environments of large fixed-route transit
      buses.

PMID- 19160909
TI  - Kinematic predictors of performance on the Star Excursion Balance Test.
AB  - CONTEXT: The Star Excursion Balance Test (SEBT) is composed of 8 reaching
      directions that are potentially measuring the same functional component, leading
      to the suggestion that the number of reach directions could be reduced without
      compromising the assessment of dynamic postural control. OBJECTIVE: To determine
      whether the relationship of stance-leg angular displacement on normalized reach
      distance is a source of dynamic-postural-control measurement redundancy. DESIGN:
      Single-session within-subjects design. SETTING: Athletic training research
      laboratory. PARTICIPANTS: 10 women and 10 men. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: Normalized reach distance and angular displacement at the knee and hip.
      RESULTS: Stepwise regression revealed that hip flexion and knee flexion,
      separately and in combination, accounted for 62% to 95% of the variance in reach
      distances. CONCLUSION: Similarity in lower extremity function could account for
      the previously observed measurement redundancy in the SEBT.

PMID- 19160910
TI  - Compensatory mechanisms in basketball players with jumper's knee.
AB  - CONTEXT: Determining whether there are compensations in those with jumper's knee
      (JK) might further our understanding of the condition. OBJECTIVE: Comparing lower
      extremity kinematics and jump performance of basketball athletes with JK with
      those of healthy controls (C). DESIGN: Repeated-measures control-match design.
      SETTING: University laboratory. PARTICIPANTS: 24 male basketball players (12 JK,
      12 C) matched by height, weight, position, experience, and frequency of play.
      INTERVENTIONS: Standing counter-movement and running layup jumps. MAIN OUTCOME
      MEASURES: Maximum vertical-jump height, footfall landing, and lower extremity
      sagittal-plane kinematics. RESULTS: There were no significant group differences
      (P > .05) in vertical-jump height (JK = 64.3 +/- 8.6 cm, C = 63.0 +/- 9.8 cm) or
      layup height (JK = 71.3 +/- 11.6 cm, C = 73.3 +/- 11.0 cm). JK subjects landed
      flat footed (50%) more than controls (8%). JK subjects showed significantly more
      hip flexion (JK = 105 degrees +/- 24.8 degrees, C = 89.8 degrees +/- 14.1
      degrees; P = .039) with decreased hip acceleration during the countermovement (JK
      = -3039 +/- 1392 degrees /s2, C = -4229 +/- 1765 degrees /s2; P = .040). When
      landing from the countermovement jump, JK subjects had significantly less knee
      acceleration (JK = -4960 +/- 1512 degrees/s2, C = -6736 +/- 2009 degrees/s2, P =
      .023) and in the layup showed significantly less ankle dorsiflexion (JK = 106.5
      degrees +/- 9.0 degrees, C = 112.5 degrees +/- 7.7 degrees; P = .048) and hip
      acceleration (JK = -2841 +/- 1094 degrees/s2, C = -3912 +/- 1575 degrees/s2; P =
      .033). CONCLUSION: Compensatory strategies observed in JK subjects might help
      maintain performance, because their jump height was similar to that of healthy
      controls.

PMID- 19160911
TI  - The effects of a supervised resistance-training program on Special Olympics
      athletes.
AB  - OBJECTIVE: To examine the effects of a resistance-training program on athletes
      with intellectual disabilities (ID). DESIGN/PARTICIPANTS: 2-way (2 x 2), repeated
      measures analysis of variance on 2 groups (males and females); 30 Special
      Olympics (SO) athletes, age 16-22 (16 males, 14 females). INTERVENTION/OUTCOME
      MEASURES: Resistance training, twice per week, for 3 months on Med-X weight
      equipment. Exercises tested: chest press, abdominal crunch, seated row, overhead
      press, seated dip, lower back extension, and biceps curl. The weight lifted and
      the number of repetitions performed were used to determine predicted 1-repetition
      max (1RM). RESULTS: All participants as a group increased significantly in
      predicted 1RM for each exercise performed. Males were stronger than females for 5
      of the 7 exercises. A significant interaction effect between genders was
      demonstrated for the seated dip. CONCLUSION: Significant strength gains can be
      accomplished by adolescents with ID via a supervised resistance-training program.

PMID- 19160912
TI  - Effect of trunk-muscle fatigue and lactic acid accumulation on balance in healthy
      subjects.
AB  - OBJECTIVE: This study sought to determine the effects of trunk-muscle fatigue and
      blood lactic acid elevation on static and dynamic balance. INTERVENTION: Fatigue
      was induced by an isokinetic protocol, and static and dynamic balance were
      assessed during bilateral stance using a Kinesthetic Ability Trainer. Subjects
      participated in a fatigue protocol in which continuous concentric movements at 60
      degrees/s were performed until the torque output for both trunk flexion and
      extension dropped below 25% of the calculated peak torque for 3 consecutive
      movements. MEASURES: Before and immediately after the fatigue protocol, blood
      lactic acid measurements and static- and dynamic-balance measurements were
      recorded. RESULTS: An increase in lactic acid levels was detected in all
      subjects. According to a dependent-samples t test, significant differences in
      balance and lactic acid values were found after the fatigue protocol. There was
      no correlation between lactic acid accumulation (change between prefatigue and
      postfatigue levels) and balance-score differences. CONCLUSION: Trunk-muscle
      fatigue has an adverse effect on static and dynamic balance.

PMID- 19160913
TI  - Kinematics and kinetics of 2 styles of partial forward lunge.
AB  - OBJECTIVE: To evaluate the anterior shift of the body's center of gravity (CG)
      and the associated inertial forces produced by 2 styles of a partial forward
      lunge. SETTING: Gait-analysis laboratory of a research institution. PARTICIPANTS:
      10 healthy volunteers. INTERVENTION: 3 trials of each lunge. MAIN OUTCOME
      MEASURES: Kinematic data were collected, and inertial reaction forces were
      resolved into net compressive and shear forces using an inverse dynamic model.
      RESULTS: Significantly (P < .001) greater anterior translation of the CG was
      found with an arms-in-front v arms-across-chest lunge style. No significant
      differences were found between the average peak inertial compressive and shear
      forces of the 2 styles (427 +/- 184 N v 426 +/- 187 N, -536 +/- 113 N v -538 +/-
      127 N). CONCLUSION: Anterior translation of the CG was larger with the arms
      forward partial-lunge position, creating increased balance demands. Both styles
      produced clinically safe (posteriorly directed) inertial shear forces, with
      greater anterior CG shift with the arms-forward style.

PMID- 19160914
TI  - Sport psychology education: a preliminary survey on chartered physiotherapists'
      preferred methods of training delivery.
AB  - OBJECTIVE: To gain an insight to the existing suggestions and recommendations on
      chartered physiotherapists' preferred methods of delivery for further training in
      sport psychology. PARTICIPANTS: 22 delegates (14 women, 8 men) from the 2006
      Association of Chartered Physiotherapists in Sports Medicine/International
      Federation of Sports Physiotherapy annual conference (response rate 53.7%).
      MEASUREMENTS: A questionnaire survey for best method of sport psychology delivery
      was developed. RESULTS: The most suitable methods for sport-psychology-training
      delivery were workshops, seminars, mentoring, and coaching. Intense training days
      and weekends were considered most appropriate. The vast majority were willing to
      travel over 50 miles to receive training, and they indicated that the most
      suitable organizations to arrange training would be professional bodies and
      associations. CONCLUSIONS: The findings provide suggestions into how further
      training in sport psychology for chartered physiotherapists could be delivered.
      To gain more detailed information on these issues, however, further research with
      a larger sample size is recommended.

PMID- 19160915
TI  - Inside the clinic: health professionals' role in their clients' psychological
      rehabilitation.
AB  - CONTEXT: Health professionals (ie, physical therapists, athletic trainers) can
      play an integral role in the psychological recovery from injury. OBJECTIVE: To
      examine health professionals' perceptions of the roles they play and their
      influence on the psychological recovery of their clients. DESIGN: A qualitative
      design using semistructured interviews that were transcribed and analyzed using
      interpretational analyses to reveal themes. SETTING: 4 rehabilitation clinics
      specializing in sport- and physical-activity-related injuries. PARTICIPANTS: 18
      participants (17 physical therapists, 1 athletic trainer) with a mean age of 36
      years. RESULTS: Using thematic coding of the interview data, general-dimension
      data themes identified were centered on the roles of rapport builder, educator,
      and communicator. Health professionals perceive that they play important roles in
      the psychological recovery of their clients in spite of a lack of professional
      training in psychology and strive to create a caring and supportive environment.
      Results demonstrate the perceptions of the roles they play and the influence they
      have on the psychological component of the recovery process.

PMID- 19160916
TI  - A comparison of the pressure exerted on soft tissue by 2 myofascial rollers.
AB  - CONTEXT: Self-myofascial release (SMR) is a technique used to treat myofascial
      restrictions and restore soft-tissue extensibility. PURPOSE: To determine whether
      the pressure and contact area on the lateral thigh differ between a Multilevel
      rigid roller (MRR) and a Bio-Foam roller (BFR) for participants performing SMR.
      PARTICIPANTS: Ten healthy young men and women. METHODS: Participants performed an
      SMR technique on the lateral thigh using both myofascial rollers. Thin-film
      pressure sensels recorded pressure and contact area during each SMR trial.
      RESULTS: Mean sensel pressure exerted on the soft tissue of the lateral thigh by
      the MRR (51.8 +/- 10.7 kPa) was significantly (P < .001) greater than that of the
      conventional BFR (33.4 +/- 6.4 kPa). Mean contact area of the MRR (47.0 +/- 16.1
      cm2) was significantly (P < .005) less than that of the BFR (68.4 +/- 25.3 cm2).
      CONCLUSION: The significantly higher pressure and isolated contact area with the
      MRR suggest a potential benefit in SMR.

PMID- 19160917
TI  - Prospering in a weak economy.

PMID- 19160918
TI  - Writing for publication: you can do it!
AB  - All rehabilitation nurses in all types of roles and settings, including students,
      have the potential to be authors. Practical advice on the 10 steps for developing
      a publishable manuscript is offered in this article. Helpful hints are provided
      for each step. Nurse authors will need to plan time for each of these steps and
      understand the work involved before beginning the journey toward publication.

PMID- 19160919
TI  - A creative alternative for providing constant observation on an acute-brain
      injury unit.
AB  - A performance improvement project to explore creative alternatives to improve the
      efficiency of constant observation was performed on an acute-brain-injury
      rehabilitation unit. The goals of the project were to increase opportunities for
      therapeutic cognitive stimulation among patients, increase nursing satisfaction
      regarding efficient use of resources to deliver rehabilitative care, decrease
      constant-observation salary costs, and maintain fall and restraint rates within
      10% of baseline. Implementing the project involved developing a new job
      description (rehabilitation patient companion) and creating a day room where
      patients receiving constant observation could go between therapies to receive
      therapeutic cognitive stimulation. The program benefited patients, staff and the
      hospital. This project illustrates how a creative alternative to constant
      observation proves beneficial on many levels and improves the delivery of
      rehabilitative care to patients with traumatic brain injury.

PMID- 19160920
TI  - Factors influencing the participation of middle-aged and older Latin-American
      women in physical activity: a stroke-prevention behavior.
AB  - Despite the known benefits of regular physical activity for preventing stroke and
      cardiovascular disease, middle-aged and older Latin-American women continue to be
      physically inactive and demonstrate a high incidence of obesity. Ethnographic
      methodology was used to explore factors that influenced this health behavior in
      25 Latin-American women. Perceptions of health, the health activities in which
      they engaged, and the factors that influenced their participation in physical
      activity comprised the three categories of responses. Facilitators and barriers
      were identified as the two primary categories and were further sorted into
      intrinsic or extrinsic factors. Conclusions of this study were that these Latin
      American women, despite multiple role demands and other barriers, participated in
      some form of physical activity; however, culturally sensitive strategies are
      needed to promote sustained physical activity in this population.

PMID- 19160921
TI  - Increase participation in your local chapter using technology.
AB  - Membership in a professional nursing organization allow nurses to interact with
      one another and can promote a higher level of excellence in patient care. This is
      especially important during a time when nurses are faced with many challenges
      from patients, families, and healthcare organizations. The rehabilitation nurses
      in South Dakota realized the importance of membership in the Association of
      Rehabilitation Nurses (ARN), however, did not have a local chapter due to the
      large distances separating the rehabilitation facilities. They organized a
      chapter uniting nurses hundreds of miles from one another using teleconference
      technology. Using technology may be a way to organize local chapters and provide
      nurses with ongoing support and learning opportunities.

PMID- 19160922
TI  - The experience of self-management in adolescent women with spina bifida.
AB  - It is essential for youth with chronic health conditions like spina bifida (SB)
      to develop self-management skills to combat vulnerability, achieve self
      sufficiency, and transition to adulthood. The purpose of this qualitative study
      was to describe the experience of self-management in 31 adolescent women with SB.
      Three themes emerged from this study: (1) opportunities to engage in self
      management activities--knowledge, skills, and aspirations; (2) dance of
      individuation--parental impact on self-management; and (3) advocacy within self
      management--confronting discrimination and stigma. The findings indicate that
      assessment and interventions to enhance self-management in adolescent women with
      SB are critical for supporting the range of condition-related and life skills
      needed for a transition to adulthood and independent living.

PMID- 19160923
TI  - A heart for justice?

PMID- 19160924
TI  - Incorporating spiritual beliefs into end-of-life care.

PMID- 19160925
TI  - Parish nursing: promoting healthy lifestyles in the church.

PMID- 19160926
TI  - Overcoming injustice in nursing and healthcare.

PMID- 19160927
TI  - Enhancing diversity in Christian nursing and education.

PMID- 19160928
TI  - Pulled in too many directions? Get a kingdom perspective!

PMID- 19160929
TI  - Setting students up for spiritual care success.

PMID- 19160930
TI  - From failed exams to nurse educator.

PMID- 19160931
TI  - A foundation of trust built on green beans.

PMID- 19160932
TI  - Facing ethical dilemmas.

PMID- 19160933
TI  - An ancient craft.

PMID- 19160934
TI  - Letting go of apathy.

PMID- 19160936
TI  - Allergy and clinical immunology. Preface.

PMID- 19160935
TI  - How do I recognize spiritual needs? Part 2.

PMID- 19160937
TI  - Interleukin-1beta targeted therapy in severe persistent asthma (SPA) and chronic
      obstructive pulmonary disease (COPD): proposed similarities between biphasic
      pathobiology of SPA/COPD and ischemia-reperfusion injury.
AB  - The histopathology of severe persistent asthma and chronic obstructive pulmonary
      disease is predominantly characterized by neutrophilic inflammation. It is
      posited that chronic hypoxia from hypoventilation in combination with
      hypoperfusion and hypercapnia are associated with induction of pulmonary tissue
      acidosis in SPA and COPD, which in turn provide ideal conditions to induce danger
      associated molecular patterns, i.e., crystallized and calcium pyrophosphate.
      These stimuli in combination with other danger-related biochemical signals are
      capable of stimulating an innate immune receptor (cryopyrin inflammasome, NALP3)
      and cause interleukin-1beta secretion with subsequent neutrophilic inflammation.
      There is evidence to suggest that the mechanisms and pathobiology associated with
      chronic hypoxia, reduced perfusion and reoxygenation in SPA/COPD may exhibit
      similarities to the biphasic pathobiology involved in ischemia-reperfusion
      injury. A rationale is suggested for trials of IL-1beta targeted therapies as an
      adjunct strategy to control neutrophilic inflammation in these conditions.

PMID- 19160938
TI  - The role of mast cells in non-allergic inflammation.

PMID- 19160939
TI  - Exploring the distal lung: new direction in asthma.
AB  - Asthma is an airway disease, yet that airway extends all the way to the alveolar
      tissue area. Pathohistiological as well as physiological and clinical studies
      have recently documented this aspect of asthma. The implications of this are
      important for all asthmatic patients, but particularly for those whose asthma is
      more difficult to control. Many of the inhaled preparations used as therapy for
      asthma are of relatively large particle size. Thus, the deposition of these
      medications is mainly in the central and medium sized airways and very little of
      a given actuation gets to the distal airways. Ultrafine inhaled steroid particles
      have been shown to reach the more peripheral portions of the airway, and
      improvement in outcome variables such as air trapping as well as symptomatic
      outcomes have been demonstrated. This review focuses on anatomic airway changes,
      physiological changes of the distal airways, clinical outcome data, and particle
      size of inhaled preparations.

PMID- 19160940
TI  - Hereditary angioedema: new hopes for an orphan disease.
AB  - Hereditary angioedema is a rare genetic disorder, manifested by recurrent edema
      leading to disfigurement, organ dysfunction and life-threatening respiratory
      impairment that may become fatal. The hallmark of HAE is C1 esterase inhibitor
      deficiency, but recent evidence points at bradykinin as the main mediator that
      causes hyperpermeability of small vasculature, leading to accumulation of edema
      fluid. Current therapeutic options for HAE are limited, and consist of drugs,
      replacement therapy, and supportive treatment. In view of many disadvantages of
      the current therapeutic modalities, new approaches to the treatment of HAE are
      now being offered. This review summarizes our experience with a new line of
      medications developed for the treatment of acute exacerbations and prophylaxis of
      HAE--icatibant: bradykinin receptor antagonist, ecallantide: kallikrein
      inhibitor, and two C1 INH preparations: Berinert-P, human plasma-derived
      concentrate, and Rhucin: novel recombinant C1-INH produced in transgenic rabbits.
      Preliminary results of these studies are encouraging and may bring new hope to
      the patients with this distressing condition. The exact number of HAE patients in
      Israel is unknown and because patients are treated individually and comprehensive
      laboratory assessment is partial, many cases might be missed or not treated
      according to accepted guidelines. We offer a new specialty center for HAE
      patients, addressing the medical and psychosocial needs of patients and their
      families.

PMID- 19160941
TI  - Ambrosia: a new impending disaster for the israeli allergic population.
AB  - The pollen of Ambrosia (ragweed) is one of the major causes of pollen-induced
      allergy worldwide. This genus of plants has apparently evolved in North America
      but later spread into Europe and Asia. Flowering of the Ambrosias starts in mid
      July and continues throughout the autumn and is a cause of major morbidity to
      allergic sensitized patients. The invasion of new species of Ambrosia into Israel
      is still in progress. Plants of Ambrosia artemisiifolia (American short ragweed),
      Ambrosia trifida (American giant ragweed), Ambrosia confertifolia, Ambrosia grayi
      and Ambrosia tenuifolia are increasingly found in Israel, mainly in the Hula
      valley in the eastern Galilee and near the Alexander River in the Sharon plain.
      From experience it is known that the time it takes to eradicate a new invasive
      species is limited. Action should be taken immediately or this new invasion will
      spread and cause a significantly increased burden of morbidity and increased
      health costs in Israel.

PMID- 19160942
TI  - Atopy in children and adolescents with insulin-dependent diabetes mellitus.
AB  - BACKGROUND: Insulin-dependent diabetes mellitus is dominated by a Th1 response
      whereas atopic diseases such as asthma, eczema and allergic rhinitis are
      characterized by a Th2 response. Because it is known that Th1 and Th2 cells
      reciprocally counteract each other, it can be speculated that the prevalence of
      Th2-mediated diseases is lower in patients with a Th1-mediated disease.
      OBJECTIVES: To compare the prevalence of atopic diseases among children with IDDM
      and age-matched controls. METHODS: The study group comprised 65 children with
      IDDM attending the pediatric endocrinology clinic at the Wolfson Medical Center.
      The control group consisted of 74 non-diabetic children who presented at the
      emergency room due to an acute illness (burns, abdominal pain, fever, head
      trauma). Patients were asked to complete a detailed questionnaire on their
      history of personal and familial atopic and autoimmune diseases. In addition, a
      total serum immunoglobulin E concentration and the presence of IgE antibodies to
      a panel of relevant inhalant allergens were analyzed. RESULTS: Children with IDDM
      and their first-degree relatives had a significantly higher prevalence of other
      autoimmune diseases such as thyroiditis and celiac as compared to controls. The
      two groups had a similar prevalence of atopic diseases with respect to history,
      total serum IgE, or the presence of IgE antibodies to a panel of relevant
      inhalant allergens. CONCLUSIONS: The prevalence of atopic diseases in IDDM
      patients was similar to that in the normal population. Our results suggest that
      the traditional Th1/Th2 theory to explain the complexity of the immune response
      is oversimplified.

PMID- 19160943
TI  - The predictive value of specific immunoglobulin E on the outcome of milk allergy.
AB  - BACKGROUND: Cow's milk allergy is the most prevalent food hypersensitivity,
      affecting 2-3% of infants, but it tends to resolve with age. Cow's milk-specific
      immunoglobulin E in the serum is an important measure in the diagnosis and follow
      up of infants and children with cow's milk allergy. OBJECTIVES: To examine the
      relation between CmsIgE and the probability of resolution of milk allergy.
      METHODS: CMsIgE was determined in the serum of 1800 infants and children referred
      for the evaluation of possible milk allergy. All children with CmslgE of 1 kU/L
      or above were followed at the allergy clinic and, according to their condition,
      underwent milk challenge. The diagnosis of cow's milk allergy was made on the
      basis of a significant and specific history or a positive oral food challenge.
      Subsequently, oral tolerance was defined as an uneventful oral challenge.
      RESULTS: A total of 135 infants and children had milk-specific IgE greater than 1
      kU/L. Forty-one percent of children still had clinical milk allergy after the age
      of 3 years. Sixty-eight percent of children older than 3 years with persistence
      of cow's milk allergy had milk-specific IgE > 3 IU/ml before the age of 1 year.
      Furthermore, 70% of children who at 3 years old had resolved their cow's milk
      allergy had milk-specific IgE that was lower than 3 IU/ml before the age of 1
      year. The positive predictive value of CmsIgE > 3 IU/ml to persistent cow's milk
      allergy at age 3 years was 82.6% (P = 0.001), with a sensitivity of 67.9% and
      specificity of 70.4%. CONCLUSIONS: Milk-specific IgE concentration in the first
      year of life can serve as a predictor of the persistence of milk allergy.

PMID- 19160944
TI  - Multiple drug allergy in patients with cutaneous adverse drug reactions diagnosed
      by in vitro drug-induced interferon-gamma release.
AB  - BACKGROUND: Multiple drug allergy syndrome is a rarely reported clinical
      condition characterized by an adverse reaction to more than one different class
      of pharmacologically and structurally unrelated drugs. The pathogenesis may
      involve immediate-type or delayed-type hypersensitivity. OBJECTIVES: To further
      characterize patients with MDA in terms of the type of CADR, drug intake and
      clinical drug suspicion. METHODS: The study group comprised 12 patients (6 males,
      6 females) with CADRs showing in vitro drug-induced IFNgamma release for multiple
      drugs, suggesting the presence of MDA. The diagnostic role of in vitro IFNgamma
      release in identifying the culprit drugs was evaluated in terms of clinical data
      and the results of in vivo tests (withdrawal and/or challenge tests) with the
      offending drugs. RESULTS: Clinical relevance was attributed to in vitro drug
      induced IFNgamma release towards multiple drugs in this series of 12 patients
      with a variety of CADRs, implying MDA. The results of in vivo tests for the
      offending drugs confirmed the diagnosis. The main causative agents responsible
      were antibiotics and non-steroidal anti-inflammatory drugs. CONCLUSIONS: The
      study further supports the role of a T cell-mediated mechanism in the
      pathogenesis of MDA. The in vitro drug-induced IFNgamma release test may serve as
      a laboratory tool to identify the culprit drugs associated with this allergy.

PMID- 19160945
TI  - Safety and efficacy of allergen immunotherapy in the treatment of allergic
      rhinitis and asthma in real life.
AB  - BACKGROUND: Subcutaneous allergen immunotherapy is effective in treating allergic
      airway disease. Disadvantages include immediate local and systemic adverse
      reactions and poor compliance. OBJECTIVES: To obtain real-life efficacy and
      safety data through a prospective observational study of SIT in the allergist's
      office. METHODS: We prospectively collected data from all patients with a
      diagnosis of allergic rhinitis and/or asthma and a specific immunoglobulin E
      mediated sensitization to one or more aeroallergens who began SIT during the 2
      year period 1 January 2005 to 31 December 2006. As part of the routine
      immunotherapy care patients were asked to complete a disease activity
      questionnaire before and yearly during the treatment. The primary outcome measure
      was the combined rhinitis and asthma symptoms scores. Data from patients
      completing at least 1 year of immunotherapy were analyzed. RESULTS: Altogether,
      133 enrolled patients with a mean age of 22.7 years completed at least 1 year of
      SIT. The allergic rhinitis and asthma disease activity score decreased from a
      mean of 8.1 to 3.3 (rhinitis) and from 4.8 to 2.4 (asthma) on a 10 cm visual
      analogue scale after 1 year of SIT (P < 0.001 for all comparisons). Rhinitis
      medication use in all patients and asthma medication use in asthmatics decreased
      significantly. Mild local adverse reactions were almost universal. There were 11
      patients (8%) who developed 14 immediate systemic, mild to moderate reactions.
      All reactions were successfully treated in the clinic; none required additional
      observation or hospitalization. CONCLUSIONS: In the hands of experienced
      allergists subcutaneous allergy immunotherapy is a safe and efficacious option
      for patients with allergic rhinitis and asthma.

PMID- 19160946
TI  - The psychological toll of the Intifada: symptoms of distress and coping in
      Israeli soldiers.
AB  - BACKGROUND: Detrimental effects of military service among the civilian
      Palestinian population have been reported in soldiers. OBJECTIVES: To examine the
      frequency and type of stressors encountered by soldiers in close contact with the
      CPP and its relationship with post-traumatic symptomatology. We also investigated
      coping methods and the preferred types of professional help. METHODS: Using
      random digit dialing methodology we conducted a phone survey of veteran soldiers,
      men (n=167) and women (n=59) in close contact with the CPP; the comparison group
      comprised male veteran soldiers with no CPP exposure (n=74). We used focus groups
      to develop context-related measures to assess exposure to violent incidents,
      coping modes and preferred modes of professional assistance. We included measures
      of traumatic exposure, post-traumatic stress symptoms and post-traumatic stress
      disorder. RESULTS: Soldiers who served among the CPP had greater exposure to
      traumatic events and to civilian-related violent incidents (more than half as
      victims, and a third as perpetrators); and 17.4% perceived their behavior as
      degrading civilians. Primary traumatic exposure, perceived health problems and
      avoidance coping were found to be risk factors for PTS and PTSD. Involvement in
      incidents that may have degraded Palestinian civilians predicted PTS.
      CONCLUSIONS: Friction with the CPP in itself does not constitute a risk factor
      for psychopathology among soldiers. However, contact with this population entails
      more exposure to traumatic events, which may cause PTS and PTSD. Furthermore, a
      relative minority of soldiers may be involved in situations that may degrade
      civilians, which is a risk factor for PTS. To avoid violent and sometimes
      degrading behaviors, appropriate psycho-educational and behavioral preparation
      should be provided.

PMID- 19160947
TI  - Congenital diaphragmatic hernia: 22 years experience in a single tertiary medical
      center.
AB  - BACKGROUND: Over the last two decades, the epidemiology, treatment strategy and
      mortality rate for congenital diaphragmatic hernia have changed. OBJECTIVES: To
      retrospectively analyze our experience with CDH of the last 22 years. METHODS: We
      reviewed the charts of all infants suffering from CDH between 1985 and 2007.
      Prenatal and maternal as well as perinatal and neonatal data were collected,
      including outcome parameters. The 71 infants that we identified were divided into
      two historical groups: from 1985 to 1995 (group 1, 23 patients) and from 1996 to
      2007 (group 2, 45 patients). RESULTS: There was an increase in the incidence of
      prenatal diagnosis and a subsequent significant decrease in gestational age at
      diagnosis in group 2 (25 weeks gestation, compared with 30 weeks gestation in
      group 1, P = 0.018). In addition, we noted a trend toward a reduced number of
      infants with right-sided hernia and associated cardiac anomalies. The timing to
      post-delivery surgery was significantly longer in group 2 (20 hours in group 1
      vs. 53 hours in group 2, P < 0.001). A significant reduction in postoperative
      mortality was demonstrated in group 2 compared with group 1 (13.5% vs. 38.7%
      respectively, P = 0.04), CONCLUSION: Our data suggest a higher survival rate for
      operated infants in group 2 during the last decade, probably due to changes in
      preoperative methods of treatment as well as later surgery timing compared to
      group 1. We speculate that today's cases of congenital diaphragmatic hernia are
      probably milder than in the past due to earlier and more detailed prenatal
      diagnosis and subsequent termination of pregnancies for the more severe forms of
      the disorder.

PMID- 19160948
TI  - Usefulness of serum myeloperoxidase in prediction of mortality in patients with
      severe heart failure.
AB  - BACKGROUND: Myeloperoxidase levels were shown to reflect endothelial dysfunction,
      inflammation, atherosclerosis and oxidative stress. OBJECTIVES: To examine the
      role of circulating myeloperoxidase, a leukocyte-derived enzyme, as a predictor
      of mortality in patients with congestive heart failure. METHODS: Baseline serum
      MPO levels were measured in 285 consecutive CHF patients and 35 healthy
      volunteers. N-terminal pro-brain natriuretic peptide and high sensitivity C
      reactive protein concentrations were also measured. The primary outcome endpoint
      was overall mortality. RESULTS: MPO levels were significantly elevated in
      patients with CHF compared to healthy volunteers (P = 0.01). During a mean follow
      up of 40.9 +/- 11.3 months there were 106 deaths. On a univariate Cox regression
      analysis MPO levels were of marginal value (P = 0.07) whereas NT-proBNP was of
      considerable value (P < 0.0001) in predicting all-cause mortality. By dividing
      our cohort according to NT-proBNP levels into high, intermediate and low risk
      groups a clear difference in mortality was shown. By further dividing the patient
      cohort according to MPO levels above or below the median (122.5 ng/ml), mortality
      prediction improved in the patients with intermediate NT-proBNP values.
      CONCLUSIONS: MPO levels are elevated in CHF and correlate with disease severity.
      MPO has an additive predictive value on mortality in patients with intermediate
      NT-proBNP levels.

PMID- 19160949
TI  - Non-traumatic rupture of spleen: can splenectomy be applied selectively?
AB  - BACKGROUND: Non-traumatic rupture of the spleen is a rare condition. It can occur
      in a pathological spleen caused by any of a variety of diseases. For yet unknown
      reasons this condition may sometimes involve an apparently normal spleen as well.
      OBJECTIVES: To examine the incidence, symptoms, causes, therapy and prognosis of
      "spontaneous" splenic rupture. METHODS: We conducted a retrospective study of
      seven patients diagnosed with splenic rupture not related to any traumatic event,
      who had been treated in the surgical department of a community hospital within
      the last 19 years. RESULTS: The male to female ratio was 5:2. In some patients,
      no background disease that could explain increased friability of splenic tissue
      could be identified. In some cases, where hemodynamic stability and absence of
      peritoneal signs afforded observation, splenectomy was delayed. In one case it
      was avoided altogether. CONCLUSIONS: "Spontaneous" rupture of spleen should be
      suspected when abdominal symptomatology occurs against a background of an acute
      infectious disease, especially in young males, or a disease known to affect
      target organs of the reticular endothelial system. Preoperative use of imaging
      studies in hemodynamically stable patients can sometimes obviate surgery, or in
      cases of massive hemoperitoneum reduce intraoperative time.

PMID- 19160950
TI  - The challenge of military adversity and the need for protective mechanisms.

PMID- 19160951
TI  - Microangiopathic antiphospholipid antibody-associated syndromes: a tribute to
      Ronald Asherson.

PMID- 19160952
TI  - Severe hemolytic uremia syndrome and antiphospholipid antibodies following bowel
      infection in the absence of major vascular occlusions: an example of MAPS?

PMID- 19160953
TI  - Hypocalcemia, prolonged QT interval and massive brain calcifications in an
      Iranian Jewish woman with APECED.

PMID- 19160954
TI  - A decade to the Israeli Center for Technology Assessment in Health Care.
AB  - The Israeli Center for Technology Assessment in Health Care (ICTAHC) was
      established in 1998 at the Gertner Institute for Epidemiology and Health Policy
      Research, on foundations set in 1992 by the Medical Technology Assessment Unit.
      The Center is defined as an independent multidisciplinary research center, whose
      main aims are to assist in developing processes for the adoption of new
      technologies, identify and propose health priorities, and serve as an educational
      center for all stakeholders. Moreover, the Center promotes working relations with
      overseas counterparts as an essential component for expansion and advancement of
      the field of health technology assessment. Throughout the years, ICTAHC had
      contributed significantly to the development of the discipline of health
      technology assessment in Israel and to actual decision making in the health care
      system. The Center had outlined the principles, guidelines and overall framework
      for technology assessment in the country, as well as substantiating the
      discipline through various research areas, which materialized into a variety of
      technology-related policy accomplishments. Today, the Center serves as a national
      focal point in the health care system in Israel, as well as maintaining an active
      position in the international milieu. It has been a decade since the
      establishment of ICTAHC. This paper reviews the evolution of the center,
      describes changes in the HTA field in Israel, identifies areas of focus and main
      research accomplishments, and illustrates the breadth of potential research scope
      and projections for the future.

PMID- 19160955
TI  - From bench to bedside: the Vth Symposium on the Biology and Treatment of Chronic
      Lymphocytic Leukemia, January 2008, Tel Aviv.

PMID- 19160956
TI  - The vulnerable patient; not the vulnerable plaque...

PMID- 19160957
TI  - [First imported case of visceral leishmaniasis in Hainan Province].

PMID- 19160958
TI  - [Gene synthesis, expression and immunogenicity analysis of TSP2 hydrophilic
      domain(TSP2HD) of Schistosoma japonicum].
AB  - OBJECTIVE: To synthesize and express the gene of TSP2 hydrophilic domain of
      Schistosoma japonicum, and investigate the immunogenicity of the recombinant
      TSP2HD protein. METHODS: The whole DNA fragment encoding the TSP2 hydrophilic
      domain was synthesized by overlapping PCR, and confirmed by DNA sequencing. The
      recombinant plasmid TSP2HD-PG was constructed by inserting the purified TSP2HD
      DNA fragment into expression vector pGEX-4T-3 and the GST-TSP2HD fusion protein
      was expressed by transforming the recombinant plasmid TSP2HD-PG into Escherichia
      coli BL21 (DE3) and induced the recombinant with isopropyl beta-D-1
      thiogalactopyranoside (IPTG). The expressing situation of fusion protein was
      analyzed by SDS-PAGE. The GST-TSP2HD fusion protein was purified by affinity
      chromatography with glutathione sepharose 4B gel, and the purified recombinant
      TSP2HD protein was prepared by digesting the GST-TSP2HD fusion protein with
      thrombin. The immuno-response of the recombinant TSP2HD recognized by the pool
      sera of schistosomiasis patients and the pool sera of heavily infected rabbits
      was explored by Western blotting analysis. The immunogenicity of the recombinant
      TSP2HD was investigated by comparing the difference of counts per minute (cpm)
      value of lymphocyte proliferation test between experiment group and control
      group. RESULTS: A 228 bp of TSP2HD gene fragment was obtained after overlapping
      PCR of three times and its DNA sequence was confirmed by DNA sequencing, which
      was same to one of the native TSP2HD. The recombinant containing recombinant
      plasmid TSP2HD-PG expressed a soluble fusion protein of GST-TSP2HD (Mr
      approximately 34 000) after being induced with IPTG. The purified recombinant
      TSP2HD protein was obtained through digesting the GST-TSP2HD fusion protein with
      thrombin. The recombinant TSP2HD was recognized by pool sera of schistosomiasis
      patients and pool sera of infected rabbits, indicating that the recombinant
      TSP2HD has a good response activity. The recombinant TSP2HD also stimulated
      proliferation of lymphocytes in infected mouse, the cpm value of experiment group
      was higher than that of the control (P < 0.01). CONCLUSION: The Sj TSP2HD gene
      has been synthesized and expressed with immunogenicity which is similar to that
      of the native antigen.

PMID- 19160959
TI  - [Suppressive effect of induced CD4+CD25+ regulatory T cells from mice infected
      with Schistosoma japonicum].
AB  - OBJECTIVE: To investigate the suppressive effect of CD4+CD25+ regulatory T cells
      from mice infected with Schistosoma japonicum. METHODS: BALB/c mice were infected
      with S. japonicum. At 6 and 13 weeks post-infection, the spleens were removed and
      CD4+CD25+ T cells were separated by magnetic beads. In in vitro experiments,
      CD4+CD25+ T Cells were cocultured with CD4+CD25- T cells. The inhibitory role of
      the CD4+CD25+ T cells was assessed by [3H] thymidine incorporation method and the
      cytokines in the cultural supernatant were detected by ELISA. In in vivo
      experiments, mice inoculated with irradiated cercariae of S. japonicum were
      adoptively transferred with CD4+CD25+ T cells isolated from the mice chronically
      infected with S. japonicum. The intracellular cytokine expressions of splenocytes
      were performed by flow cytometry, and sera IgG1 and IgG2a antibodies against
      irradiated cercaria antigens were detected by ELISA. RESULTS: In vitro, CD4+CD25+
      T cells were able to suppress the proliferation of CD4+CD25- T cells when
      stimulated with SEA, compared with single CD4+CD25- T cells culture (cpm 7615 +/-
      1 058) (P < 0.01). Furthermore, CD4+CD25+ T cells isolated from mice chronically
      infected with S. japonicum presented higher suppressive efficacy (cpm 2 336 +/-
      490), compared with that isolated from the acutely infected mice (cmp 4 467 +/-
      144) (P < 0.05). Meanwhile, CD4+CD25+ T cells isolated from mice with the acute
      infection inhibited the cytokine secretion by CD4+CD25- T cells and the
      suppression rate was 32.0% for IL-4 (P < 0.05), 66.3% for IFN-gamma (P < 0.01)
      and 63.2% for IL-2 (P < 0.01), respectively, and CD4+CD25+ T cells isolated from
      mice with the chronic infection, the suppression rate was 28.4% for IL-4 (P <
      0.05), 60.1% for IFN-gamma (P < 0.01) and 58.3% for IL-2 (P < 0.01),
      respectively. In vivo, IFN-gamma secretion and IgG2a antibody production of mice
      adoptively transferred with CD4+CD25+ T cells from the chronically infected mice
      were suppressed when mice were inoculated with irradiated cercariae of S.
      japonicum (P < 0.05). CONCLUSION: CD4+CD25+ T cells isolated from mice infected
      with S. japonicum have played roles of Th1-dominant immune suppression.

PMID- 19160960
TI  - [Up-expression of PD-1-PD-L induced by immunization with SEA and SMWA of
      Schistosoma japonicum in mice].
AB  - OBJECTIVE: To explore the expression of PD-1-PD-L pathway of mice immunized with
      soluble egg antigen (SEA) or soluble male worm antigen (SMWA) of Schistosoma
      japonicum. METHODS: Eighteen BALB/c mice were randomly divided into three groups
      named as control group (A), SEA immunized group (B) and SMWA immunized group (C).
      Mice in groups B and C were subcutaneously immunized weekly with SEA (50 microg)
      and SMWA (50 microg) of S. japonicum respectively. After 4 times immunization,
      the expression of programmed death-1 (PD-1), programmed death-ligand1 (PD-L1) and
      PD-L2 in splenic cells was measured with flow cytometer. The expression of IL-4
      and IFN-gamma in cultural suspension of splenic cells was detected by sandwich
      ELISA after stimulation with ConA. RESULTS: The expression ratio of PD-1, PD-L1
      and PD-L2 was extremely low in the control group, but increased after the
      immunization with SEA and SMWA. The expression ratio of PD-1 was (8.24 +/- 1.31)%
      in SEA immunized mice, higher than the mice immunized by SMWA [(6.08 +/- 1.28)%].
      PD-L2 was much more elevated in SEA immunized mice [(5.26 +/- 1.73)%] while PD-L1
      more significantly increased with SMWA immunization [(10.82 +/- 2.33)%]. In
      addition, the up-expression of PD-L1 was associated with the level of IFN-gamma
      and the expression of PD-L2 was associated with IL-4 secretion. CONCLUSION: The
      expression of PD-1-PDL was up-regulated in BALB/c mice immunized by SEA or SMWA
      of S. japonicum.

PMID- 19160961
TI  - [Establishment of two-dimensional differential gel electrophoresis using
      cerebrospinal fluid from neurocysticercosis patients].
AB  - OBJECTIVE: To establish the method of two-dimensional differential gel
      electrophoresis and obtain high resolution 2D images from cerebrospinal fluid
      (CSF) of patients with neurocysticercosis. METHODS: CSF samples were collected
      from four patients diagnosed as neurocysticercosis clinically and by ELISA,
      computed tomography (CT) or magnetic resonance imaging (MRI), and from four
      healthy subjects without neurological disorders. The CSF samples were
      precipitated with cold acetone, then pooled by equal amount as patients and
      controls. The internal standard comprised equal amounts of proteins extracted
      from both groups. Internal standard, and proteins from the two groups were
      labeled prior to electrophoresis with spectrally resolvable fluorescent dyes,
      cyanein dye2 (Cy2), Cy3 and Cy5. Sodium dodecylsulfonate polyacrylamide gel
      chromatography (SDS-PAGE) and two-dimensional differential in-gel electrophoresis
      (2-D DIGE) of labeled samples were then run. The differential expressed proteins
      showed in the images of SDS-PAGE and 2-D DIGE gels scanned with 488 nm, 532 nm
      and 633 nm wavelength laser were analyzed by ImageQuant and DeCyde 5.0
      respectively. Spot detection and quantification was performed for the
      differential in-gel analysis (DIA) module of DeCyder. Biological variation
      analysis (BVA) module of DeCyder was matched gel 1 and gel 2 images to provide
      data on differential protein expression levels between the two groups. RESULTS:
      The ImageQuant result displayed that the CSF protein was compatible with the dye,
      and the difference of protein amount was revealed by the difference of
      fluorescence intensity. DIA indicated that there were 896 and 894 protein dots on
      gel 1 and gel 2 respectively, and 90% of them were matched each other. BVA showed
      that there were 55 protein spots with different expressional level between
      neurocysticercosis and control groups. Protein spots with two-fold increase or
      decrease were 47 and 8 respectively in neurocysticercosis patients compared with
      healthy controls. CONCLUSION: The method of 2-D DIGE has been established with
      high-resolution images for the examination of cerebrospinal fluid, providing a
      foundation for further study of neurocysticercosis comparative proteomics.

PMID- 19160962
TI  - [Prophylactic immunization of dangguibuxue decoction against Cryptosporidium
      infection in immune suppressed mice].
AB  - OBJECTIVE: To explore the prophylaxis of dangguibuxue decoction, a traditional
      Chinese medicine made from Angelica sinensis and Radix astragalus, on
      immunosuppressed mice infected by Cryptosporidium parvum. METHODS: 48 BALB/c mice
      were randomly divided into 4 groups: normal control (A), immunosuppressed control
      (B), high dose (C), and low dose (D). Mice in groups B, C and D were
      intragastrically administered with dexamethasone (DXM) for 8 days, and in the
      same time mice in groups C and D were given high dose (2 g/kg) and low dose (1
      g/kg) dangguibuxue decoction respectively. On the ninth day all mice in groups B,
      C and D were orally inoculated by 1 x 10(6) oocysts of C. parvum. The amount of
      oocysts in feces was examined daily since being infected. 11 days after
      infection, the subset of T lymphocytes in peripheral blood was analyzed with flow
      cytometry, sIL-2R in serum and sIgA of intestinal fluid were detected by ELISA.
      Pathological change of duodenum and jejunum was observed microscopically.
      RESULTS: Compared with the immuno-suppressed control group, there were less
      oocysts in feces (35.0 +/- 4.21) (P < 0.01) and lighter injury in the intestinal
      mucosa in mice of the high dose dangguibuxue decoction group. Both the number of
      CD4+ T lymphocytes (47.483 +/- 4.082) and the ratio of CD4+/CD8+ (2.271 +/-
      0.378) increased, sIgA [(320.19 +/- 1.94) ng/ml] in the intestinal fluid elevated
      and sIL-2R [(321.34 +/- 6.66) ng/ml] in peripheral blood decreased in the high
      dose group, with a significant difference in comparison to the immunosuppressed
      group (P < 0.01). All the above-mentioned indices in low dose dangguibuxue
      decoction group showed no significant difference with the immunosuppressed
      control group (P > 0.05). CONCLUSION: Administration of high dose dangguibuxue
      decoction plays a role of prophylaxis on the infection of C. parvum in
      immunosuppressed mice through improving the immune status.

PMID- 19160964
TI  - [Expression analysis of antibacterial peptide genes at different development
      stages of Musca domestica].
AB  - OBJECTIVE: To explore the expression level of antibacterial peptide genes at the
      different development stages of Musca domestica. METHODS: Total RNA was extracted
      from eggs, 1st instar larvae, 2nd instar larvae, 3rd instar larvae, pupae and
      adults of M. domestica. After the primers for antibacterial peptide (cecropin,
      defensin and attacin) genes and GAPDH were designed respectively according to the
      reported M. domestica gene sequences in GenBank, semi-quantitative RT-PCR was
      performed to detect expression level of these genes in the development stages of
      M. domestica using GAPDH as inner control. RESULTS: The antibacterial peptide
      genes were detected with bands of 210 bp, 300 bp and 650 bp at all development
      stages of M. domestica. The expression level in the 3rd instar larvae and adults
      were higher, with a band value of cecropin, defensin and attacin in relation to
      GAPDH of 1.61, 1.99, 1.62 and 1.47, 1.92, 1.59, respectively; while it was lower
      at eggs, 1st instar larvae and pupae with a band value of cecropin, defensin and
      attacin 0.49, 0.49, 0.42 and 0.72, 0.49, 0.64 and 0.65, 0.39, 0.91, respectively.
      CONCLUSION: The antibacterial peptide genes express at all development stages of
      M. domestica with an evidently different expression level.

PMID- 19160963
TI  - [ITS and 28S rDNA-LSU sequence analysis of Orientobilharzia turkestanicum from
      bovine and caprine hosts].
AB  - OBJECTIVE: To explore sequence differentiation of ITS and 28S rDNA-LSU of
      Orientobilharzia turkestanicum from bovine and caprine hosts. METHODS: Adult
      worms of O. turkestanicum from the naturally infected cattle, sheep, cashmere
      goat and goat were collected and identified morphologically as O. turkestanicum
      according to existing keys and descriptions. The genomic DNA was extracted from
      parasites of different hosts. The internal transcribed spacer (ITS, contains ITS
      1, 5.8S nuclear ribosomal DNA, ITS-2) and 28S nuclear ribosomal DNA-LSU were
      amplified by PCR, sequenced and analyzed by Chromans and DNASTAR softwares, and
      the RNA secondary structure of 28S rDNA-LSU was analyzed by DNAMAN software.
      RESULTS: ITS-1, 5.8S rDNA, ITS-2 and 28S rDNA-LSU of O. turkestanicum from bovine
      and caprine hosts were 384, 159, 331 and 1 304 bp, respectively. ITS-1 and 5.8S
      rDNA of O. turkestanicum from different definitive hosts were identical; ITS-2 of
      O. turkestanicum from cattle, sheep and cashmere goat were identical, with one
      nucleotide variation compared with that of goat; 28S rDNA-LSU of O. turkestanicum
      from sheep and cashmere goat were identical, with two nucleotides variation
      compared with that of cattle and goat. The RNA secondary structure of 28S rDNA
      LSU of O. turkestanicum from caprine hosts were identical or similar, but with
      large variation compared with that of cattle. CONCLUSION: The rDNA sequence from
      different definitive hosts shows nucleotide variations to some extent and the RNA
      secondary structure of 28S rDNA-LSU from caprine hosts shows large variation in
      comparison to that of bovine.

PMID- 19160965
TI  - [Genetic variation and clustal analysis of Trichomonas vaginalis cysteine
      proteases].
AB  - OBJECTIVE: To clone the genes coding for cysteine proteases (CPs, TvCPs) from
      Trichomonas vaginalis and to analyze their genetic variations with the related
      sequences from NCBI database (GenBank) and T. vaginalis Genome Project database
      from The Institute for Genomic Research (TIGR). METHOD: TvCP genes were amplified
      using PCR, and inserted into vector pET28b or pBS-T. The recombinant plasmids
      were then transformed to Escherichia coli BL21 or Topl0 strain. The recombinant
      plasmids were used for sequencing. Homologous TvCP genes were blasted based on
      NCBI GenBank and TIGR T. vaginalis Genome Project database. The sequences of
      cloned TvCP genes were aligned and clustered by Clustal X (1.83 version) with
      retrieved sequences. Comparisons of amino acids among cathepsin L-like TvCPs,
      human L-like cathepsins and papaya papain were performed using DNAstar software,
      and their phylogenic tree was constructed based on neighbor-joining method using
      Clustal X. RESULTS: Two TvCP3 clones and one TvCP2 had a high identity of more
      than 99% with their responding TvCPs. Three clones of TvCP4 genes, GZ-CP4-clone 1
      3, belonged to two members of a family showing a high percentage identity of more
      than 97.5% with the sequences of TvCP4 genes from databases (GenBank and TIGR)
      both at amino acid and nucleotide levels. Nine homologous TvCP4 pro-enzymes with
      304 amino acids and other two members with deletions of N-terminal sequence
      existed in T. vaginalis sharing a similarity of 62.3-96.7% amino acids, which may
      evolve by means of gene replication and deletion. TvCP1-4, TvCP12, TvCP25 and
      CP65 had an identity of 61-88.2% at amino acid levels. So far, all reported
      sequences of C1 family from T. vaginalis belonged to capanthesin L-like subfamily
      with the same enzymatic active sites, conserved cysteine residues and similar
      structural features such as ERFNIN-like motif in pro-enzyme region, suggesting
      that they might result from gene duplication and mutations. CONCLUSION: TvCPs
      belong to cathepsin L-like family with genetic diversity, but they have the same
      active amino acid residues, cysteine residues and similar structural
      characteristics, suggesting that they may derive from one ancestor.

PMID- 19160966
TI  - Cloning and sequencing of the gene encoding variant-specific surface antigen from
      Giardia lamblia.
AB  - OBJECTIVE: To clone and sequence variant-specific surface antigen gene from
      Giardia lamblia isolate SUCH/89/BTMR/2(C2) derived from human in China. METHODS:
      Total genomic DNA of G. lamblia was extracted and a full-length variant-specific
      surface antigen gene fragment was amplified by polymerase chain reaction (PCR).
      The PCR product was cloned into pMD19-T simple-vector, transformed into an
      Escherichia coli JM109 strain and then sequenced. The sequence analysis for
      cloned fragment was finished by Vector NTI 9.0 software for the homology of
      Giardia variant-specific surface antigen gene to that of sequences published in
      GenBank. RESULTS: The full-length variant-specific surface antigen gene fragment
      from G. lamblia was found to be 2 142 bp, encoding a 713 amino acid polypeptide
      and contained a single open reading frame (ORF). The deduced polypeptide sequence
      was rich in cysteine (11.8 mol%), most of which occurred with in 29 copies of the
      4-amino acid CXXC motif, one GGCY-tetrapeptide motifs and three NXS consensus N
      linked glycosylation sites. This polypeptide was also rich in threonine (10.2
      mol%), glycine (12.1 mol%) and alanine (10.1 mol%). Like other previously
      identified VSPs, it contained a highly conserved hydrophobic C-terminal region.
      The homology of G. lamblia SUCH/89/BTMRI/2(C2) variant-specific surface antigen
      gene to that of sequence (TSA417) published in GenBank was 99% both at the
      nucleotide and the amino acid levels. CONCLUSION: The full length variant
      specific surface antigen gene from the isolate of G. lamblia has the common
      characteristics with other previously identified VSPs.

PMID- 19160967
TI  - [Morphology of III stage larvae of Angiostrongylus cantonensis in Pomacea
      canaliculata].
AB  - OBJECTIVE: To observe the morphologic characteristics of III stage larvae of
      Angiostrongylus cantonensis from Pomacea canaliculata. METHODS: P. canaliculata,
      the intermediate host snail of A. cantonensis, was infected with I stage larvae
      of A. cantonensis in laboratory. After 61 days, III stage larvae of A.
      cantonensis were harvested from snail's lungs and muscle of head-foot, followed
      by HE stain to observe morphological characteristics. RESULTS: The whole body of
      III stage larva was curling with obtuse head. Its pharyngeal canal extends from
      the buccal hole on the top of the head to the intestines at the pharyngeal
      intestine joint place, with apex cauda and clear anal tube. The tegument of the
      III stage larva was eosin-stained, with a transparent sheath outside of tegument.
      Some of the larvae cauda showed in circular cylinder, and some larvae presented
      ventral gland with two very short uterine which used to be the feature only
      showed in early IV stage larva. CONCLUSION: Morphologically characteristics of
      the III stage larvae is helpful to better understand the life-cycle and the
      control of A. cantonensis.

PMID- 19160968
TI  - [Evaluation indices of social burden caused by advanced schistosomiasis].
AB  - OBJECTIVE: To study the evaluation indices and their weights of social burden
      caused by advanced schistosomiasis so as to provide scientific basis for control
      of the disease. METHODS: Primary indices of social burden evaluation for advanced
      schistosomiasis were summarized based on literature review. Secondary indices
      were put forward by a brainstorming process of experts. After the first round
      Delphi method, the secondary indices that needed were chosen, and the importance
      of primary indices was prioritized. Through the second and third round Delphi
      method, the weight of each secondary index was obtained. RESULTS: Four primary
      indices and 16 secondary indices consisted the index system of social burden
      induced by the disease. According to the significance, the 4 primary indices were
      arranged as social economy, government image, public psychology and social
      security. The weight of "funding for schistosomiasis control from central and
      local governments" in "social economic" stood the largest (14.063), while that of
      "equity to patients" in "government image", the smallest (3.125). CONCLUSION: The
      study covers all major aspects and their significance in social burden of
      advanced schistosomiasis, and an evaluation index system has been established for
      field validation.

PMID- 19160969
TI  - [On a new checklist of the anopheline mosquitoes in China with rectification for
      some specific names].
AB  - This paper presents a new revised "Checklist of the Anopheline Mosquitoes in
      China" based on the development of the mosquito-taxonomic researches during the
      years of 1988-2007. The new checklist contained 61 species (subspecies) of
      anopheline mosquitoes all in China. Twelve species among the past records were
      omitted because of their invalid specific names which were allocated into
      following categories: (1) A doubtful record in China, with no typical specimen up
      to date since last century, e.g. Anopheles campestris reported in Yunnan; (2)
      Misidentification: An. atroparvus and An. indiensis; (3) Confirmed as synonyms by
      hybridizing experiments or molecular identification, including 9 species as
      follows: An. changes, An. dazhaius, An. kiangsuensis, An. anthropophagus, An.
      kunmingensis, An. xiaokuanus, An. junlianensis, An. yutsushiroensis (part) and
      An. fluviatilis. Meanwhile, the following rectified 4 anopheline mosquito species
      should be added to the new checklist: An. belenrae, An. lester, An. pulls, and
      An. baimaii.

PMID- 19160970
TI  - [Impact of host factors on the schistosome-killing process induced by
      praziquantel].
AB  - Experimental studies indicated that the killing process of schistosomes induced
      by praziquantel comprises two aspects, i.e. the direct effect of praziquantel on
      schistosomes and the host immune reaction. The former one appears in stimulation
      of worm activity, spasmodic contraction of worm musculatures and severe damage to
      the tegument, which results in hepatic shift of schistosomes, influence on the
      nutrition absorption, excretion/secretion and defense function of the tegument,
      followed by the secondary interference with the worm metabolism. While the latter
      one involves the destruction of the host concomitant immune mechanism after
      tegumental damage and peeling, which is unfavorable for worm survival.
      Particularly, the exposure of the worm surface antigen provides a target which
      can be attacked by specific antibodies. Therefore, the antischistosomal activity
      of praziquantel is immune-dependent. In this paper some host factors involved in
      the killing process of schistosomes induced by praziquantel were summarized.

PMID- 19160971
TI  - [Informatics analysis of malate dehydrogenase from Taenia saginata asiatica].
AB  - Tools from bioinformatics websites such as NCBI, ExPaSy were used for the
      analysis. The malate dehydrogenase full-length gene from Taenia saginata asiatica
      was 1 212 bp in length, with a coding region of 30-1 028 bp and coding 332 amino
      acids. It was a complete and full-length gene compared with the homologues in
      GenBank. The protein showed no transmembrane region, with stable physical
      chemical characteristics. Three major linear epitopes located aa95-aa100, aa322
      aa327 and aa117-aa122, with certain distance from each other on the surface of
      spatial structure of malate dehydrogenase (MDH). The last one was the linear
      epitope of Taenia. This cytosolic malate dehydrogenase gene is a potential
      antigen for diagnosis.

PMID- 19160972
TI  - [Prediction for helper T cell epitopes and its application in vaccine development
      against parasite infection].
AB  - Cellular immunity plays an important role in defense against diseases, such as
      pathogenic infection, autoimmunity and tumor. With the progress of molecular
      immunology, mechanisms of T cellular immunity, and the T cell epitopes and
      functional genomics, studies on the prediction based on data-derived for T cell
      epitopes has been highlighted, and could be one of the useful tools for
      application in vaccine development. This review summarizes theory and methodology
      of prediction for helper T cell epitopes, and their application in vaccine
      development against parasites, and new research directions are also discussed.

PMID- 19160973
TI  - [Historical review on the classification and rectification of Anopheles
      anthropophagus to An. lesteri in China].
AB  - This paper deals with the taxonomic status and specific names of Anopheles
      anthropophagus and An. lesteri, the important malaria transmitting vector in
      China. Based on a historical review of the literature recorded from the country,
      substantial evidence from morphological and molecular biological studies gives
      reason to convince that An. anthropophagus is a synonym of An. lesteri. A
      resurrection of the specific name of An. lesteri Barisas et Hu, 1936 brooks no
      delay.

PMID- 19160974
TI  - [Preliminary evaluation on the transmission potential of visceral leishmaniasis
      after earthquake in Wenchuan].
AB  - Data of visceral leishmaniasis cases since 2005 were collected through the
      National Infectious Disease Monitoring System. Number of reported cases in 2005,
      2006, 2007 and January to June in 2008 was 59, 49, 77 and 30 in Sichuan Province,
      and 92, 106, 162 and 83 respectively in Gansu Province. With an increase of the
      number of stray dogs and susceptible human population, damage of the medical
      services including diagnosis and treatment capacity after the earthquake, there
      might be a strengthened transmission potential and possible spread of the
      disease.

PMID- 19160975
TI  - [Improved staining method for permanent specimen of Fasciolopsis buski].
AB  - Fasciolopsis buski specimens were collected, fixed with neutral formalin fixative
      solution, stained with alum-carmine staining solution, discolored with 2% kalium
      alum. The fixed and stained specimen shows clear internal structure with bright
      color, and can be stored for long time.

PMID- 19160976
TI  - [Malaria cases among those worked in and returned from Uganda].

PMID- 19160977
TI  - [Twenty years of "the world war" against AIDS. Is there a chance for victory?].

PMID- 19160978
TI  - [HIV/AIDS and national security].

PMID- 19160979
TI  - SMART control stents in femoropopliteal region.
AB  - INTRODUCTION/AIM: Occlusive disease of lower limb arteries have been so far
      traditionally best treated with bypass surgery, but we want to find minimally
      invasive approach that should be at least as good as conventional surgery, and
      hopefully better. The aim of this study was to evaluate SMART Control stents
      (Cordis, J&J) in Trans Atlantic Society Consensus (TASC) B and C femoropopliteal
      lesions during one-year follow-up. METHODS: Retrospective nonrandomized analysis
      included forty arteries in consecutive 40 patients who were stented with SMART
      Control stents. Primary patency at 12-month verified with Duplex Ultrasound and
      Acute Brachial Index (ABI) as well as freedom from Target Vessel
      Revascularization (TVR) were primary endpoints. RESULTS: Primary technical
      success at stent implantation was 100%. Mean ABI values were preprocedurally
      0.50, postprocedurally 0.83, at one month 0.86, at six months 0.84, at one year
      0.78. After one year 39 stents were patent (97.5%). CONCLUSION: Excellent
      performance of the stent from technical point of view and a midterm results in
      vessel patency, as well as the absence of need for TVR were achieved. Yet, life
      expectancy in this cohort group of patients demands longer follow up data to draw
      a definite sustained positive conclusion.

PMID- 19160980
TI  - [Use of mechanical ventilation in pediatric patients].
AB  - BACKGROUND/AIM: Major aims of mechanical ventilation (MV) in pediatrics mean the
      contribution to complete recovery of acute disorder or to establishing stability
      of previously long-term changed health condition. MV is used today in 16-46% of
      patients treated in pediatric intensive care units. The aim of this paper was to
      get insight into the presence of the disease and pathologic conditions and
      outcome of MV regarding previous health condition of pediatric patients. METHODS:
      This retrospective study included 476 pediatric patients (beyond neonatal age)
      who underwent mechanical ventilation (MV). On the basis of previous health status
      the patients were classified in two groups: the group A consisted of 157 children
      with no previous chronic disease leading to MV and the group H comprised of 319
      children who received MV due to worsening ofprevious chronic disease. RESULTS: In
      both groups of pediatric patients there was significant predominance of younger
      age patients. Acute and chronic neurological disorders were the most frequent
      conditions requiring use of MV. Out of a total number (476) of the patients, 178
      patients (37.40%) died. In the group A 17 patients (10.9%) died, while in the
      group H mortality rate was significantly higher (161 or 50.5% patients died; p <
      0.01; RR 4.85; CI 3.1-7.6). Total duration time of MV in all the patients was 7
      525 days, with 1 345 days (15%) accounted for the group A and 4 567 days (85%)
      for the group H. Mean MV duration was 7.48 (+/- 9.23) days for the patients in
      the group A which is significantly shorter in comparison to mean 21.8 (+/- 57.96)
      days for the group H patients (p < 0.001). CONCLUSION: These results point out
      significant contribution of MV to better outcome in pediatric patients with
      different acute disorders. Clear dominance of chronically ill children requiring
      mechanical ventilation due to acute worsening of their condition implies new
      complexity of problems regarding organization of pediatric intensive care and
      treatment.

PMID- 19160981
TI  - Matrix metalloproteinases (MMP-1, -8, -13) in chronic periapical lesions.
AB  - BACKGROUND/AIM: Matrix metalloproteinases (MMPs) are proteolytic enzymes capable
      of degrading almost all extracellular matrix and basement membrane components in
      many destructive pathological processes, such as chronic inflammation and bone
      destructive lesions. The aim of this study was to determinate the correlation
      between concentration of collagenases (MMP-1, -8, -13) in chronic periapical
      lesions and their dimension calculated with software predilection through X-ray.
      METHODS: Chronic periapical tissues were collected by periapical surgery from 60
      teeth with clinically and radiographically verified different chronic periapical
      lesions (20 granulomas, 20 diffuse periapical lesions, 10 cysts). Ten normal
      pulps used as controls were obtained by extirpation of the pulp of impacted third
      molars after their surgery. For rapid analysis of MMP-1, -8, -13 collagenase
      activities in the examined material Chemicon Collagenase Activity Assay Kit were
      used. From the X-ray trough software predilection (Image Tool3 Program) of the
      volume of chronic periapical tissue, correlation between concentration of MMPs in
      the periapical lesions and their dimension was confirmed. RESULTS: Different
      concentrations of collagenases (MMP-1, -8 and -13) in chronic periapical process
      from different inflammation types showed different activity of MMPs. The obtained
      results showed the highest values of collagenases concentration (MMP-1, -8, -13)
      in chronic diffuse lesions (5.39 ng/ml). Low values of concentration of MMPs
      accompanied less serious lesions, whereas chronical periapical lesions of large
      dimension had high concentration of MMPs, which was proportional to progression
      of the lesion and destruction of bone tissue. CONCLUSIONS: This study confirmed
      the destructive role of collagenases (MMP-1, -8 and -13) in inflammation process,
      which directly depends on the concentration of MMPs in pathologically changed
      tissue.

PMID- 19160982
TI  - [An outbreak of trichinellosis in a military unit].
AB  - BACKGROUND/AIM: In December 2001, an outbreak of trichinellosis spreaded in a
      military unit. The aim of this paper was to show possibilities and consequences
      of trichinellosis infestations in military units during peace time, as well as to
      improve knowledge and awareness of medical corps personnel, commanders and
      soldiers about this disease. METHODS: A descriptive and analytical
      epidemiological models were used to find out a source of outbreak and to identify
      the ways of its transmission. RESULTS: This outbreak was caused by the
      contaminated raw smoked sausage which had not undergone health inspection and
      brought from civilians to a military unit. Thirty-eight persons were exposed,
      twenty-one affected and hospitalized. The most frequent symptoms reported were
      fever (76.2%), myalgia (76.2%), palpebral edema (42.8%), face edema (19.0%) and
      diarrhea (14.3%). Test for indirect immunofluorescence was positive in 14.3% and
      ELISA test was positive in 28.6% of the patients. Eosinophilia was present in
      85.7% of the affected. IgE values were increased in 28.6% and CPK values were
      increased in 61.9% of the diseased. All of the 17 exposed undiseased had negative
      laboratory analyses for trichinellosis. CONCLUSION: We propose intensifying
      health education and continuing the implementation of duly supervised and
      evaluated self-check programs. A well-tuned, fast-reacting epidemiological
      monitoring system has to be obligatory.

PMID- 19160983
TI  - Cardiovascular morbidity and mortality in patients treated with hemodialysis-
      epidemiological analysis.
AB  - BACKGROUND/AIM: Cardiovascular diseases are the leading cause of death in
      patients treated with hemodialysis (HD). The annual cardiovascular mortality rate
      in these patients is 9%. Left ventricular (LV) hypertrophy, ischemic heart
      disease and heart failure are the most prevalent cardiovascular causes of death.
      The aim of this study was to assess the prevalence of traditional and
      nontraditional risk factors for cardiovascular complications, to assess the
      prevalence of cardiovascular complications and overall and cardiovascular
      mortality rate in patients on HD. METHODS: We investigated a total of 115
      patients undergoing HD for at least 6 months. First, a cross-sectional study was
      performed, followed by a two-year followup study. Beside standard biochemical
      parameters, we also determined cardiac troponins and echocardiographic parameters
      of LV morphology and function (LV mass index, LV fractional shortening, LV
      ejection fraction). The results were analyzed using the Student's t test and Mann
      Whitney U test. RESULTS: The patients with adverse outcome had significantly
      lower serum albumin (p < 0.01) and higher serum homocystein, troponin I and T,
      and LV mass index (p < 0.01). Hyperhomocysteinemia, anemia, hypertriglyceridemia
      and uncontrolled hypertension had the highest prevalence (86.09%, 76.52%, 43.48%
      and 36.52%, respectively) among all investigated cardiovascular risk factors.
      Hypertrophy of the LV was presented in 71.31% of the patients and congestive
      heart failure in 8.70%. Heart valve calcification was found in 48.70% of the
      patients, pericardial effusion in 25.22% and disrrhythmia in 20.87% of the
      investigated patients. The average annual overall mortality rate was 13.74%,
      while average cardiovascular mortality rate was 8.51%. CONCLUSION: Patients on HD
      have high risk for cardiovascular morbidity and mortality.

PMID- 19160984
TI  - [Cerebrospinal fluid amyloid beta and tau protein: biomarkers for Alzheimer's
      disease].
AB  - BACKGROUND/AIM: Introduction of acetylcholine esterase inhibitors as a
      symptomatic treatment of Alzheimer's disease (AD) has additionally highlighted
      the importance of diagnostic markers in cerebrospinal fluid (CSF) for early AD
      diagnosis: low level of 42 amino acid form of amyloid-beta peptide (Abeta42), and
      levels of tau protein (T-tau) and phosphorylated tau protein (P-tau). The aim of
      this study was to diagnostic potential of CSF biomarkers T-tau, P-tau and Abeta42
      as biochemical markers for AD. METHODS: Lumbar puncture was performed in 63
      patients with AD and 26 control subjects who passed orthopedic surgery. The
      Innotest, ELISA sandwich test (Innogenetics - Belgium) was used for measuring the
      levels of T-tau, P-tau and Abeta342. RESULTS: The patients and the control group
      did not differ in age, education and sex. Mean levels of CSF T-tau and P-tau were
      significantly higher in the patients with AD (p < 0.001) compared to the control
      group, in contrast to significantely lower CSF Abeta42 in AD group (p < 0.001). A
      significant progressive decrease of Abeta42, as well as significant progressive
      increase of T-tau and P-tau was found among AD subgroups (according to MMSE
      staging) and controls. CONCLUSION: The obtained results suggest that these
      biomarkers may be supportive in the diagnosis of AD, especially in the early
      course of the disease and could be used in the routine clinical practice
      considering the approaching target therapeutics.

PMID- 19160985
TI  - The effects of polarized light therapy in pressure ulcer healing.
AB  - BACKGROUND/AIM: Neglecting polarized light as an adjuvant therapy for pressure
      ulcers and methodology distinctions in the trials engaging polarized light are
      the reasons for many dilemmas and contradictions. The aim of this study was to
      establish the effects of polarized light therapy in pressure ulcer healing.
      METHODS: This prospective randomized single-blind study involved 40 patients with
      stage I-III of pressure ulcer. The patients in the experimental group (E) were
      subjected, besides polarized light therapy, to standard wound cleaning and
      dressing. Standard wound cleaning and dressing were the only treatment used in
      the control group (C). A polarized light source was a Bioptron lamp. Polarized
      light therapy was applied for six min daily, five times a week, four weeks. The
      Pressure Ulcer Scale for Healing (PUSH) was used in the assessment of outcome.
      Statistic analysis included Mann Whitney Test, Fisher Exact Test, Wilcoxon Signed
      Rank test. RESULTS: There were significant differences between the groups at the
      end of the treatment regarding the surface of pressure ulcer (E: 10.80 +/- 19.18;
      C: 22,97 +/- 25,47; p = 0.0005), rank of pressure ulcer (E: 5.90 +/- 2.48; C: 8.6
      +/- 1.05; p = 0.0005) and total PUSH score (E: 7.35 +/- 3.17; C: 11.85 +/- 2.35;
      p = 0,0003). The patients in the experimental group had significantly better
      values of the parameters monitored than the patients in the control group.
      CONCLUSION: After a four-week polarized light therapy 20 patients with stage I
      III ulcer had significant improvement in pressure ulcer healing, so it could be
      useful to apply polarized light in the treatment of pressure ulcers.

PMID- 19160986
TI  - [Microcirculatory disorders in ischemic/reperfusion hepatic injury].

PMID- 19160987
TI  - [Why dual X-ray absorptiometry is the gold standard in diagnosing osteoporosis].

PMID- 19160988
TI  - [Endovascular treatment of carotid-cavernous fistula type A with platinium
      coils].
AB  - BACKGROUND: Carotid-cavernous fistulas are abnormal communications between
      carotid arteries or their branches and the cavernous system caused mostly by
      trauma. Posttraumatic fistulas represent 70% of all carotid-cavernous fistulas
      and they are mostly high-flow shunts (type A). This type gives characteristic eye
      symptoms. CASE REPORT: This paper presents a 44-year old male patient with
      carotid-cavernous fistula as a result of penetrating head injury. In clinical
      presentation the patient had exophthalmos, conjunctival chemosis and weakening of
      vision on the right eye, headache and diplopia. Digital subtracted angiography
      showed high-flow carotid-cavernous fistula, which was vascularised from the left
      carotid artery and from vertebrobasilar artery. Endovascular embolization with
      platinum coils was performed through the transarterial route (endoarterial
      approach). Check angiogram confirmed that the fistula was closed and that no new
      communications developed. CONCLUSION: Embolization of complex carotid-cavernous
      fistula type A was successfully performed with platinum coils by endovascular
      approach.

PMID- 19160989
TI  - Atypical proliferating mucinous tumors of gigantic dimensions.
AB  - BACKGROUND; Ovarian tumors of low malignant potential (LMP) are also known as
      atypically proliferating tumors. Ovarian tumors of LPM account for approximately
      15% of all epithelial ovarian cancers. Mean age of occurrence is 40 years and
      they are 15-20 cm in diameter. CASE REPORT: A 32-year-old female patient was
      hospitalized as an urgent case with a large tumor mass that filled the entire
      abdomen. Cyst was 100 x 70 cm dimensions belonging to the right ovary and filled
      with 18 liters of content. Right adnexectomy, resection of the second ovary, as
      well as biopsy of the omentum were performed. Lymphadenectomy of the right iliac
      and obturator area was also performed. After receiving definitive
      histopathological results it was decided to perform a radical reoperation. On the
      10th postoperative day relaparotomy, total hysterectomy and left adnexectomy were
      performed. The patient was released on the 6th postoperative day. She used to
      come to regular examinations up to date. CONCLUSION: This case is a proof that
      LMP tumors have low malignant potential, they grow slowly and can reach great
      proportions.

PMID- 19160990
TI  - [Evidence-based medicine as "free will"].

PMID- 19160991
TI  - [Radical cystectomy and urinary diversion: assistance to patient choice].
AB  - The patient who undergoes radical cystectomy requires a urinary diversion which
      will significantly impact on his everyday life. He will have to choose with his
      surgeon between three different types of diversions that enable urine to flow out
      of his body adequately. Hence, preoperative information is of paramount
      importance. The team providing it needs an iconographic support, unfortunately
      not readily available. In order to clearly explain to the patient the various
      types of diversions that he may benefit from, their everyday care and to have
      him/her share the experiences of previous patients, we have elaborated a multi
      disciplinary information sequence associated with the creation of video support.

PMID- 19160992
TI  - [Cancer and masculine sexuality].
AB  - Oncology treatments are changing the sexual function of 75% patients. A clear
      communication with the medical staff and the wife's patient and a
      multidisciplinary approach with the general practitioner, the surgeon, as well as
      with a sexologist and a physiotherapist and occasionally a psychologist or a
      psychiatrist, are highly suggested to eliminate misunderstanding or the early use
      of erectogenic medication, are some measures that can be taken to reduce the side
      effects of oncological treatment on sexual life.

PMID- 19160993
TI  - [Treatment of localized prostate cancer: the role of robotic radical
      prostatectomy].
AB  - Robotic prostatectomy has progressively emerged as an oncologic and functional
      equivalent to the gold standard of open surgery, with minimally invasive
      advantages such as a short hospital stay, less blood loss and early return to
      complete activity. However, mastering the technique remains delicate and requires
      regular and sufficient practice to reach the aforementionned advantages. Because
      of the marketing pressure, there is now a plethora of robots available in some
      areas. This will lead to the multiplication of occasional operators, whose
      negative impact on the efficiency of the procedure is demonstrated. The solution
      may be that of aviation: improve skills on a simulator in order to correctly
      perform clinically. It is now necessary to stimulate the elaboration of such a
      simulator.

PMID- 19160994
TI  - [Partial nephrectomy in renal cancer: a new standard?].
AB  - Rising renal cell carcinoma incidence is in relationship with early diagnosis
      during radiological exams. Radical nephrectomy was the gold standard treatment
      for 30 years. Partial nephrectomy is nowadays a validated therapeutic option for
      renal cell carcinoma up to 7 cm with comparable oncological results associated
      with better life quality and survival. Partial nephrectomy is tricky and
      laparoscopic approach remains reserved for expert centers.

PMID- 19160995
TI  - [Laparoscopic nephrectomy: technical aspects].
AB  - The laparoscopic approach has emerged as a valid option for surgical management
      of kidney cancer, as well as a few benign pathologies. The immediate benefits of
      laparoscopy are well established and include less estimated blood loss, decreased
      pain, shorter perioperative convalescence, and improved cosmesis. Long-term
      oncologic outcomes of patients treated laparoscopically for kidney tumors are
      similar to those of open surgery.

PMID- 19160996
TI  - [Minimally invasive ablation techniques for small kidney tumors: cryoablation and
      radiofrequency].
AB  - Over the last years, the development of minimally invasive surgery using
      percutaneous or laparoscopic ablative techniques for the treatment of small renal
      tumours has become more common. Cryotherapy and radiofrequency option have been
      now integrated in the armamentarium of the urologist. These approaches seem to be
      an attractive alternative to extirpative surgery in selected high-risk patients
      and offer on a short time basis equivalent cancer control to conventional
      surgery. This review presents recent data with regard to the use of cryotherapy
      and radiofrequency in the treatment of small renal tumours. These techniques will
      obviously have to stand the test of time.

PMID- 19160997
TI  - [Echoes at the meeting of the European Society of Cardiology].

PMID- 19160998
TI  - [Use of telemedicine in Switzerland].
AB  - In the 21st century, telemedicine has become daily business. Nevertheless, they
      are still a lack of precise definitions of telemedicine. Legal and financial
      implications of telemedical applications are complex, with lots of local
      restrictions, far beyond global technological aspects. In the United States,
      telemedicine is a reality since decades, and is basically defined as the
      provision of health care when distance separates the participants. Technology and
      networks for telemedicine are universally globalized, but the legal and financial
      implications are diametrically more local based. Any CT-scan made at midnight in
      Switzerland can be accurately assessed within minutes by any Australian
      radiologist, for whom it will be the morning, and so far around the globe at any
      time of the day or the night. But how will the billing work intercontinentally?
      And what about legal implications of this telemedical service? In this paper, we
      review the actual definitions of telemedicine, check our local legal
      responsibilities, and present the Tarmed financial positions for billing.

PMID- 19160999
TI  - [First successful transplantation of reconstructed trachea].

PMID- 19161000
TI  - [More or less significant statistics].

PMID- 19161001
TI  - [Rebound of the case of Myriad Genetics].

PMID- 19161002
TI  - [Ruptures].

PMID- 19161003
TI  - [Nurses at the razor's edge].

PMID- 19161005
TI  - [Elections of the National Council of Order of Nurses].

PMID- 19161004
TI  - [Position of nurses in the shadow of a new era].

PMID- 19161006
TI  - ["A bill for health that is solid for our citizens"].

PMID- 19161007
TI  - [Society of nurses, 23 regions, 23 presidents].

PMID- 19161008
TI  - [Preventing pain induced by care].

PMID- 19161009
TI  - [Masters of public health develop new competence].

PMID- 19161010
TI  - [The French experiment with rapid detection of AIDS].

PMID- 19161011
TI  - [The National Society of Nurses supports health care reform].

PMID- 19161012
TI  - [Systematic determination of diabetic microangiopathy combined with therapeutic
      education].

PMID- 19161013
TI  - [The connection with help, a humanistic approach to nursing. Complex care at the
      heart of the nursing profession].

PMID- 19161014
TI  - [The connection of help, an extremely technical concern].

PMID- 19161015
TI  - [The connection of help and nurses, regulatory and conceptual aspects].

PMID- 19161016
TI  - [Case of the relation of nursing and palliative care].

PMID- 19161017
TI  - [The function of help in rehabilitation].

PMID- 19161018
TI  - [Training students in relation to help, a pedagogic definition].

PMID- 19161019
TI  - [Point of view of a psychologist].

PMID- 19161020
TI  - [Supervision in the area of a nursing clinic].

PMID- 19161021
TI  - [10/10. Nutrition of aged persons].

PMID- 19161022
TI  - [10/11, The patient in orthopedic traction].

PMID- 19161023
TI  - [2/5, Fibromyalgia].

PMID- 19161024
TI  - Physician-owned specialty hospitals: friend, foe-or (system) failure?

PMID- 19161025
TI  - U.S. health care and the first four months of Obama.

PMID- 19161026
TI  - Shared sacrifices, shared responsibilities will be key.

PMID- 19161027
TI  - Leonard L. Berry, PhD: The Mayo culture of leadership.

PMID- 19161029
TI  - Implementing electronic health records: 10 factors for success.
AB  - Strategies for maximizing the value of an EHR implementation include:
      Establishing clear strategies, objectives, and plans for EHR implementation.
      Including managers and clinicians in discussions on ways to tie the EHR in with
      the organization's strategy and areas requiring improvement. Continually
      measuring performance of EHR-enabled processes. Investing in critical
      infrastructure. Maintaining efficient and effective IT governance.

PMID- 19161028
TI  - Recovering FICA tax paid on resident stipends: time for a strategic review.
AB  - Teaching hospitals often have tens of millions in FICA-tax refund claims pending
      with the IRS-claims that reach back to taxes paid in the mid-1990s. Court
      decisions rendered over the past few years in this area have been positive for
      teaching hospitals and their residents. In light of recent trends, it would be
      prudent for teaching hospitals to update their strategies for moving these long
      pending refund claims forward to a successful resolution.

PMID- 19161030
TI  - Strategies for reducing bad debt.

PMID- 19161031
TI  - The long view: how the financial downturn will change health care.
AB  - There are five reasons that today's economic downturn will have a much broader
      impact on U.S. health care than did past recessions: This downturn is likely to
      be more severe and last longer. Healthcare organizations are experiencing
      problems from several directions simultaneously. Healthcare organizations entered
      this downturn more heavily leveraged and more vulnerable. This downturn is
      notjust a recession, but a major realignment for financing practices. As the
      realignment occurs and the new financing order sorts itself out, healthcare
      organizations are not likely to receive the favorable treatment they had in the
      past.

PMID- 19161032
TI  - Developing leadership talent in healthcare organizations.
AB  - Effective initiatives for developing and retaining leadership talent are built
      around five supporting elements: Identification of key leader competencies.
      Effective job design. A strong focus on leadership recruitment, development, and
      retention. Leadership training and development throughout all levels of the
      organization. Ongoing leadership assessment and performance management.

PMID- 19161033
TI  - Beyond economics 101: insights into healthcare reform from the Congressional
      Budget Office.

PMID- 19161034
TI  - Maximizing nursing productivity the benefits of improved collaboration between
      nursing and support services.
AB  - Benefits of increased collaboration between nursing and support services
      personnel--some of which have positive financial implications for hospitals-
      include: More effective use of nursing resources. Improved patient, nurse,
      physician, and staff satisfaction. Higher levels of nurse retention. Decreased
      hospital-acquired infections.

PMID- 19161035
TI  - Target: zero hospital-acquired infections.
AB  - Hospital-acquired infections (HAIs) take a significant toll not only on patients,
      but also on a hospital's bottom line. By taking a zero tolerance approach to
      HAIs, hospital leaders can improve patient safety and financial performance.
      Eliminating HAIs requires clear goals, a committed leadership, access to
      resources, a best-practice mindset, effective people management, and ongoing
      vigilance.

PMID- 19161036
TI  - Getting care levels right from beginning to end.
AB  - To enhance management of admissions and length of stay, hospitals should: Review
      the processes that clinical decision technology will support, and revamp those
      processes as necessary. Create clearly defined processes. Identify a physician
      champion and support his/her effort to lead the change necessary for adoption of
      improvement processes. Collect data to evaluate the program. Encourage clinical
      collaboration.

PMID- 19161037
TI  - Start small and build toward business intelligence.
AB  - To use business intelligence effectively, healthcare organizations should start
      small, align organizationally, and leverage success. Organizations should
      determine which measures they need and how to present them. Organizations should
      reinvest savings to continually improve.

PMID- 19161038
TI  - The not-for-profit investment committee in tough times.

PMID- 19161039
TI  - How not to get fired.

PMID- 19161040
TI  - How to manage the unmanageable.
AB  - In today's volatile financial environment, those responsible for managing an
      organization's investment risk will be tested and challenged. The risk management
      process described in this article can be effectively implemented within any
      healthcare organization by following three broad steps: Assemble a cross
      functional team to define the risk management priorities of your organization.
      Educate all of the people involved in relevant aspects of risk management. Foster
      an environment that supports collaboration and open dialogue. The collaborative
      approach to risk management is a people-dependent process. First and foremost,
      risk management is about people, the decisions that they make, and how well they
      work together daily.

PMID- 19161041
TI  - Change.

PMID- 19161042
TI  - Pregnancy and labor alternative therapy research.

PMID- 19161043
TI  - Improving the science for botanical and dietary supplements.

PMID- 19161044
TI  - The map: integrating integrative medicine.

PMID- 19161045
TI  - Confirmation of the efficacy of ERr 731 in perimenopausal women with menopausal
      symptoms.
AB  - OBJECTIVE: In a previous study, the special extract ERr 731 of Rheum rhaponticum
      significantly reduced vasomotor and other menopausal symptoms associated with
      perimenopause. This trial was conducted to confirm the efficacy of ERr 731.
      DESIGN: A multicenter, randomized, placebo-controlled, clinical trial with 112
      perimenopausal women with menopausal symptoms receiving either 1 enteric-coated
      tablet of ERr 731 (n = 56) or placebo (n = 56) daily for 12 weeks. Primary
      outcome criterion for efficacy of ERr 731 compared to placebo was the change of
      the Menopause Rating Scale (MRS) total score from day 0 to day 84. Other efficacy
      assessments analyzed included the number and severity of hot flushes, individual
      symptoms of the MRS, treatment outcome, and various safety parameters. RESULTS:
      By 12 weeks, ERr 731 caused a highly significant reduction of the MRS total score
      from 27.0 +/- 4.7 points to 12.4 +/- 5.3 points when compared to the placebo
      induced decrease from 27.0 +/- 5.3 points to 24.0 +/- 6.2 points (P < .0001). A
      significant reduction in each individual MRS item score, in hot flushes and the
      hot flush weekly weighted score, together with a marked improvement in treatment
      outcome were also observed (P < .0001). These results confirm the efficacy of ERr
      731 in alleviating menopausal symptoms in perimenopausal women. Fourteen adverse
      events were reported in total: 11 by 5 women receiving ERr 731 and 3 by 3 women
      receiving placebo. ERr 731 was well tolerated by the majority of the women.
      CONCLUSION: ERr 731 was confirmed to be effective for the treatment of menopausal
      symptoms in perimenopause.

PMID- 19161046
TI  - Clinical observations and seven-and-one-half-year follow-up of patients using an
      integrative holistic approach for treating chronic sinusitis.
AB  - CONTEXT: Despite the widespread popularity of alternative medical approaches to
      respiratory and allergic disorders, there is a lack of scientific substantiation
      of their benefits. OBJECTIVE: Assessment of the therapeutic benefit of an
      integrative holistic approach to the treatment of chronic sinusitis. DESIGN:
      Patients began a 5-month program consisting of 5 evening sessions of 2 hours each
      in October of 1999. SETTING: The program was held in the offices of one of the
      authors (WSS). PATIENTS: Ten patients of an allergist-immunologist specialist
      (WSS), symptomatic despite aggressive conventional treatment for their chronic
      sinusitis, were recruited to participate in an integrative holistic medical
      education and treatment program consisting of 5 sessions and evaluated at a 1
      year follow-up. Sessions consisted of education in lifestyle and indoor-air
      modification, nasal hygiene, and treatment with fluconazole. Eight of 9 subjects
      were located and provided feedback 7 years and 6 months later, in June 2007. MAIN
      OUTCOME MEASURES: Health-related quality of life (QOL) was assessed using the
      short-form QOL survey (SF-12) and rhinitis QOL by the Rhinitis Quality of Life
      Questionnaire (RQLQ). RESULTS: No significant differences emerged in the SF-12 or
      mini-RQLQ scores comparing visit 2 with visit 1. Statistically significant
      improvement for physical and mental subscales of the SF-12 emerged comparing the
      results of visit 4 with visit 2 after the addition offluconazole treatment to the
      regimen, persisting through an additional year of follow-up. Feedback at 7.5
      years confirmed marked long-term improvement in chronic sinusitis symptoms
      compared to their pre-study condition.

PMID- 19161047
TI  - Diets based on Ayurvedic constitution--potential for weight management.
AB  - CONTEXT: Ayurveda, the traditional Indian medical system, is receivingincreasing
      attention worldwide. OBJECTIVE: A retrospective study was conducted to determine
      the effectiveness ofAyurvedic constitution-based diets on weight loss patterns of
      obese adults. DESIGN, SETTING, SUBJECTS, AND INTERVENTION: Records of 200 obese
      adults, both male and female, who had completed 3 months of the diet therapy at
      Ayurvedic clinics, were examined and data collated. Techniques used included a
      checklist of personality traits, physical signs, and food likes and dislikes to
      determine the dosha. Based on the predominant doshas, diets were prescribed and
      closely monitored for a period of 3 months. OUTCOME MEASURES: Records of height
      and weight and chest, abdominal, waist, arm, and thigh circumferences noted
      initially and after each month for the period of 3 months were obtained. RESULTS:
      Among the 200 subjects, 55 (27.5%) were vatta-, 83 (41.5%) were pitta-, and 62
      (31.0%) were kapha-predominant. At the beginning, kapha and pitta people were
      heavier than vatta people. After the 3 months of therapy, the pitta group lost
      the most weight (9.84%). The decrease in all the anthropometric measurements was
      higher in pitta and kapha people than in vatta individuals. Hence, diets based on
      Ayurvedic constitution may prove useful in promoting weight loss. Though these
      promising findings support traditional Indian Ayurvedic scriptures, more closely
      controlled trials are needed to substantiate these findings.

PMID- 19161048
TI  - Delivery of a full-term pregnancy after TCM treatment in a previously infertile
      patient diagnosed with polycystic ovary syndrome.
AB  - There is a growing body of literature supporting the use of traditional Chinese
      medicine (TCM) for increasing the likelihood of conception and carrying a
      pregnancy to term. The use of TCM in fertility treatment is becoming more widely
      recognized, and several clinical trials are being supported by the National
      Center for Complementary and Alternative Medicine to assess the efficacy of such
      treatments, as evidenced by the listings in the National Institutes of Health's
      Computer Retrieval of Information on Scientific Projects (CRISP) database. In
      addition to subjecting TCM to the rigors of Western scientific standards, it is
      important that TCM and other CAM practitioners share their expertise and
      practical experiences through case reports in the same spirit that their Western
      medical counterparts do. This dissemination of knowledge is critical in
      increasing awareness about TCM within the broader scientific community. The
      clinical case report presented here describes the course of TCM treatment that
      resulted in a successful pregnancy in a previously infertile woman who had been
      diagnosed with polycystic ovary syndrome (PCOS). It also illustrates the
      importance of the need for collaborative efforts between TCM and Western medical
      practitioners.

PMID- 19161049
TI  - The use of botanicals during pregnancy and lactation.
AB  - Women are the largest consumers of healthcare, and this extends to their
      utilization of complementary and alternative medicine (CAM). Researchers have
      attempted to uncover the reasons why women turn to CAM in general and to
      botanical medicine in particular. Desire to have personal control over their
      health has been cited as the strongest motive for women to use herbal medicine.
      Second was dissatisfaction with conventional treatment and its disregard for a
      holistic approach, as well as concerns about the side effects of medications.'
      These concerns may explain, in part, the fact that many women use herbal remedies
      during pregnancy. A survey of 578 pregnant women in the eastern United States
      reported that 45% of respondents had used herbal medicines, and a survey of 588
      women in Australia revealed that 36% had used at least 1 herbal product during
      pregnancy. Women probably feel comfortable using herbal remedies because of their
      perceived safety, easy access, and the widespread availability of information
      about them (ie, Internet, magazines, books). While it is true that many
      botanicals are mild in both treatment effects and side effects, the data
      regarding safety during pregnancy are very limited. Given the small sample sizes
      in clinical trials studying botanicals in pregnant women, only large differences
      in measures of pregnancy outcomes would likely be detected. For example, if an
      herb were thought to increase the rate of spontaneous abortion from 6% to 7%, a
      sample size of more than 19000 women would be needed. It is highly unlikely that
      there will be any studies of a botanical (or drug) with this large a sample size.
      So when addressing the safety of an herb during pregnancy, we must look at the
      totality of the evidence, which includes traditional and contemporary use, animal
      studies, pharmacological studies, and clinical trial data, when available. Survey
      data tell us that women often do not share their use of herbal remedies with
      their healthcare providers due to fear of offending providers or to the belief
      that clinicians will be ignorant about their use. Practitioners should maintain
      an open and respectful demeanor when counseling pregnant and nursing women about
      the use of botanical medicines, and they should know how to access unbiased and
      authoritative information sources, so they may reliably answer questions on
      inadvertent exposures and provide guidance on herbal products that might be
      beneficial.

PMID- 19161050
TI  - A possible central mechanism in autism spectrum disorders, part 2:
      immunoexcitotoxicity.
AB  - In this section, I explore the effects of mercury and inflammation on
      transsulfuration reactions, which can lead to elevations in androgens, and how
      this might relate to the male preponderance of autism spectrum disorders (ASD).
      It is known that mercury interferes with these biochemical reactions and that
      chronically elevated androgen levels also enhance the neurodevelopmental effects
      of excitotoxins. Both androgens and glutamate alter neuronal and glial calcium
      oscillations, which are known to regulate cell migration, maturation, and final
      brain cytoarchitectural structure. Studies have also shown high levels of DHEA
      and low levels of DHEA-S in ASD, which can result from both mercury toxicity and
      chronic inflammation. Chronic microglial activation appears to be a hallmark of
      ASD. Peripheral immune stimulation, mercury, and elevated levels of androgens can
      all stimulate microglial activation. Linked to both transsulfuration problems and
      chronic mercury toxicity are elevations in homocysteine levels in ASD patients.
      Homocysteine and especially its metabolic products are powerful excitotoxins.
      Intimately linked to elevations in DHEA, excitotoxicity and mercury toxicity are
      abnormalities in mitochondrial function. A number of studies have shown that
      reduced energy production by mitochondria greatly enhances excitotoxicity.
      Finally, I discuss the effects of chronic inflammation and elevated mercury
      levels on glutathione and metallothionein.

PMID- 19161051
TI  - Frank Lipman, MD: where Eastern medicine meets Western medicine. Interview by
      Frank Lampe and Suzanne Snyder.

PMID- 19161053
TI  - Emergence of the doctor of nursing practice degree.

PMID- 19161055
TI  - Low-level-laser therapy as an alternative treatment for primary herpes simplex
      infection: a case report.
AB  - Gingivostomatitis is the most common primary and symptomatic clinical
      manifestation of HSV-1 infection. Painful oral lesions appear as ulcerative
      erosions on the gingiva, palate, buccal mucosa, and tongue, leading to eating and
      drinking difficulties with an evolution between 10-14 days. This paper describes
      a case of a 19-month-old boy with severe painful Gingivostomatitis lesions. Low
      level laser therapy (LLLT) was used with an immediate outcome.

PMID- 19161054
TI  - Dentists on stamps.

PMID- 19161056
TI  - Periodontal conditions associated with space maintainers following two different
      dental health education techniques.
AB  - The aim was to investigate the effect of fixed and removable space maintainers on
      periodontal status of children and to compare the efficiency of verbal and
      written dental health education. 52 healthy children aged between 7-10 years who
      will be treated with fixed or removable appliances were divided into two
      subgroups to whom were given verbal and written dental education. Plaque index,
      bleeding index and mean pocket depth scores of the teeth were recorded at
      baseline and 3, 6 and 9 months after application. Plaque, bleeding index and mean
      pocket depth scores showed significant difference in the appliance groups in the
      follow-ups. Plaque index scores displayed a positive correlation with the
      duration of both appliances. The difference between pocket depth scores were
      found to be significant in the follow-ups in both appliance groups while it was
      insignificant between education groups and significant increase in bleeding index
      scores was observed in both appliance groups and education techniques given. It
      is concluded that both removable and fixed space maintainers can result in
      inflammation on periodontal tissues of the children.

PMID- 19161057
TI  - Clinical analysis of molar fissures by Cone-beam tomography.
AB  - This study aimed to validate clinical analysis of 20 pediatric dentists on
      occlusal groove-fossa-system of molar depth comparing to Cone-beam tomography.
      The 48 sound third molars were visually classified from the shallowest to the
      deepest. Images were taken from the Accuitomo 3DX. There was a fair correlation
      between clinical analysis and the tomographic scorings (rs = 0.238; P = 0.103).
      It was concluded that pediatric dentists were not able to classify the fissures
      depth by visual analysis correctly.

PMID- 19161058
TI  - The prevalence and surface distribution of caries among schoolchildren in Ankara,
      Turkey according to their dental health behaviors.
AB  - The aim of this study was to classify children according to their oral hygiene
      behaviors at the elementary school, and to evaluate the effects of oral health
      behaviors on caries prevalence, and to calculate the number of carious teeth and
      the surface distribution of caries in school children during a 2-year follow-up
      period. Results shows that even in the presence of the acquisition of appropriate
      oral hygiene behavior during preschool period, dental professionals and
      educational system should supported oral health motivation in primary school.

PMID- 19161059
TI  - Evaluation of an educational program for children with high risk of caries.
AB  - The goal of this study was to evaluate a 15-month educational program designed to
      children. The sample consisted of 60 six-year olds, randomly assigned into
      control and experimental group. The control consisted of tooth brushing training,
      once a year. The experimental group received intensive individual tooth brushing
      training every three months and guidance on oral health. Initially, both groups
      were assessed using plaque, gingival, dmfs and DMF-S indexes every three months.
      In the control, no statistically significant difference was observed for plaque
      and gingival indexes. The experimental group showed a statistically significant
      reduction in mean values for two indexes. The caries indexes showed no
      statistically significant difference. The proposed educational program developed
      was efficient in reducing gingival and plaque indexes as well caries incidence.

PMID- 19161061
TI  - Giant cell granuloma in a child: case report.
AB  - This article describes a case of central giant cell granuloma in the right
      posterior region of mandible in a 10-year-old girl. The lesion was removed by
      curettage and a histopathological examination was carried out. Clinical and
      radiographic follow-up showed total removal of the lesion. The importance of
      early diagnosis of this type of lesion is emphasized, mainly in children.

PMID- 19161060
TI  - Effect of mixing process on microleakage of glass ionomer cements used in
      atraumatic restorative treatment on primary molars.
AB  - Aiming to assess the effect of mixing process on microleakage, 40 primary molars
      were filled with encapsulated glass ionomer cements (GICs) (Vidrion, RCaps and
      Fuji, IXGPFAST) or with GICs stored in bottles (Vidrion, R and Fuji, IX). Dye
      penetration was assessed using scores. Encapsulation and mechanical mixing have
      reduced significantly marginal microleakage levels in class II restorations
      performed with conventional GICs if compared to the values obtained by their
      bottled correspondents (p=0.000).

PMID- 19161062
TI  - Prevalence of oral Candida species ina North American pediatric population.
AB  - Oral candidiasis caused by species other than Candida albicans has been observed.
      This study evaluated the prevalence of oral yeast species among 196 children
      during routine oral exam. Based on standard mycological testing, 130 (66%)
      subjects had fungal growth. Candida albicans isolates were recovered in 56% of
      children, but an extensive diversity in the non-albicans species was observed.
      Intrinsic differences in the pediatric population may favor the presence of yeast
      species other than C. albicans.

PMID- 19161063
TI  - Oral and dental findings in osteopetrorickets.
AB  - While dental findings of both rickets and osteopetrosis have been reported, there
      is no published report on the oral and dental findings of osteopetrorickets. In
      this paper dental findings of osteopetrorickets were presented. A two-year-old
      female child was referred to the pedodontics clinic for dental examinations
      before bone marrow transplantation. Her teeth showed severe mobility and the
      eruption of the teeth were delayed. The dental findings of the patient were
      different from that of osteopetrosis and rickets.

PMID- 19161064
TI  - Assessment of oral complications in children receiving chemotherapy.
AB  - The aim of this study was to assess the early oral complications in pediatric
      patients receiving chemotherapy. An interview and oral examination was conducted
      on 150 pediatric cancer patients receiving standard dose chemotherapy. Results
      showed that oral pain and dry mouth were the most frequent patients' complaints.
      The prevalences of chemotherapy-induced oral mucositis and oral infections were
      relatively high. The chemotherapeutic antimetabolites were the most frequently
      associated with oral complications than other types of chemotherapy. The present
      results indicate that the oral complications among patients receiving
      chemotherapy are common.

PMID- 19161065
TI  - Enamel hypoplasia in children with renal disease in a fluoridated area.
AB  - The aim of this study was to compare the frequency of enamel hypoplasia in
      children with renal disease and healthy children, all of whom live in a
      fluoridated area. A cross-sectional study was made in 42 children divided into 2
      groups. To describe enamel changes, 3 diagnostic criteria were applied: TSIF
      Index to describe dental fluorosis, Jackson-Al-Alousi Index to describe enamel
      hypoplasia, and Russell criteria to differentiate mild forms of dental fluorosis
      and enamel hypoplasia. The frequency of enamel hypoplasia in patients with renal
      disease was 38.09%. This frequency is smaller than that seen in other studies.
      There was no difference in the frequency of dental fluorosis between patients
      with renal disease and patients without renal disease. However the patients with
      renal disease presented more severe dental fluorosis than children without renal
      disease.

PMID- 19161066
TI  - Dimensional changes in dental arches after treatment with a prefabricated
      functional appliance.
AB  - The purpose of this study was to determine the effect of the T4K, a prefabricated
      functional appliance, on the transverse and anterior-height dimensions of the
      maxillary and mandibular dental arches. Dimensions before and after treatment
      were measured on the sample, then, natural growth was subtracted from the
      treatment effects and compared with twice the error of the method. A clinically
      significant increase of both dimensions was observed in the maxilla and mandible
      when Class II malocclusion patients were treated with the T4K. Therefore, this
      retrospective study demonstrates that T4K is a valid treatment choice at an early
      age when transverse expansion is part of the treatment goal.

PMID- 19161067
TI  - Functional appliance therapy to control drooling: a case of a child with mental
      retardation.
AB  - A 12 year old male child with mental retardation was referred to the department
      of Pedodontics and Preventive Children Dentistry, AB Shetty Memorial Institute of
      Dental Sciences, Mangalore, with a complaint of severe drooling. Mouth closure
      exercises and speech therapy had failed to control the problem. The patient was
      given a functional appliance and a significant reduction in the severity of the
      drooling and reduction in the foul odor was found. Despite its limitations
      functional appliance therapy could serve as a useful alternative to the use of
      drugs or surgery in the control of drooling.

PMID- 19161068
TI  - Changes of tongue position and oropharynx following treatment with functional
      appliance.
AB  - The aim of this study was to determine changes of tongue position and
      oropharyngeal space following treatment with functional appliance in patients
      with class II div I malocclusion. In this before-after clinical trial, 28
      patients with class II div I malocclusion were investigated. The range of age of
      females was 10-13 years and males 11-14 years. These samples were treated for II
      months. McNamara analysis and some linear variables were used to determine
      positional changes of tongue and oropharyngeal space. In this study, tongue moved
      significantly (P. value < 0.05) forwards in the horizontal dimension and non
      significantly downwards in the vertical dimension. Treatment with functional
      appliance leads to significant alterations in tongue position and significantly
      increases the extent of oropharyngeal space.

PMID- 19161070
TI  - Low birth weight as a risk factor for infant mortality in Egypt.
AB  - We examined the risk of infant mortality among low-birth-weight children (< 2500
      g) controlling for other risk factors of infant mortality. We used survival
      regression analysis on 11,361 childbirths in the 5 years preceding the 2000 Egypt
      Demographic and Health Survey. Higher birth order; shorter birth interval; lack
      of prenatal care, safe sources of drinking-water and hygienic toilet facilities;
      living in urban residence and Upper Egypt rural region were associated with a
      higher isk of infant mortality. The multivariate model indicated that low-birth
      weight children were about 3 times more likely to die in infancy than other
      children (hazard ratio = 2.89, 95% CI: 2.33-3.58) independent of other risk
      factors.

PMID- 19161071
TI  - Knowledge, attitudes and practices of Iraqi mothers and family child-caring women
      regarding breastfeeding.
AB  - We assessed breastfeeding knowledge, attitudes and practices of 3413 Iraqi
      mothers and adult female relatives in the same household and their association
      with sociodemographic characteristics. The majority of the women (73.1%)
      initiated breastfeeding early after delivery, 92.9% believed colostrum was good
      for their baby and 64.6% breastfed on demand. However, knowledge was lacking
      about full exclusive breastfeeding until 6 months postpartum, signs of good
      positioning and latch-on and the correct to introduce supplements. Nearly 35%
      believed that breast milk was not enough for their infants. Rural and less
      educated women knew less about breastfeeding concepts than more educated urban
      women but more continued breastfeeding longer and introduced supplements later.

PMID- 19161072
TI  - Pattern and severity of rheumatic valvular lesions in children in Khartoum,
      Sudan.
AB  - We determined the pattern and severity of valvular involvement in 100 Sudanese
      patients with rheumatic heart disease (RHD) in 2 centres in Khartoum in 2003. All
      the patients underwent history taking, physical examination and Doppler
      echocardiography. The commonest lesions were mitral regurgitation (84%) and
      aortic regurgitation (40%). Mitral stenosis alone was uncommon (9%) which could
      be due to a low detection rate related to the slow stenotic process and the
      subtle early signs. This, together with the inconsistent history of rheumatic
      fever, may lead to an underestimate of the prevalence of RHD. There was a strong
      correlation between severity of the lesion and irregular prophylaxis (P < 0.001).

PMID- 19161073
TI  - Frequency of Escherichia coli O157:H7 in children with diarrhoea in Zahedan,
      Islamic Republic of Iran.
AB  - Escherichia coli O157:H7 has been implicated in diarrhoea, dysentery,
      haemorrhagic colitis and uraemic haemolytic syndrome but is not routinely
      cultured in laboratories. We tested 322 samples from children referred with
      diarrhoea to a clinic in Zahedan, Islamic Republic of Iran. There were 21
      sorbitol-negative E. coli isolated; serotyping revealed 4 strains positive for
      O157, out of which only 2 strains were identified as E. coli O157:H7. Both cases
      were boys, aged 1.5 and 4 years respectively. Antibiotic sensitivity testing
      found the strains were sensitive for amikacin, gentamicin, nitrofurantoin and
      tobramycin and resistant to chloramphenicol, cefalexin, cefalothin and co
      trimoxazole.

PMID- 19161074
TI  - Seroprevalence of hepatitis A virus antibodies among a sample of Egyptian
      children.
AB  - We determined the seroprevalence of hepatitis A virus antibodies (HAV Ab) among
      296 Egyptian children aged 2.5-18 years of different social classes to ascertain
      whether to give HAV vaccine early in life or to leave children to acquire natural
      immunity. Overall 61.4% were seropositive for HAV Ab. There was a significant
      increase in the seroprevalence of HAV Ab with higher age and lower social class;
      in children aged < 6 years, 72.7% of high and 19.0% of low social class were
      seronegative for HAV Ab. A national vaccination programme for HAV is not a
      priority. We recommend vaccination against hepatitis A for high social class
      children at the preschool period without testing for HAV. Vaccination for middle
      social class children can be done, but only after testing for HAV.

PMID- 19161075
TI  - Age-specific rubella seroprevalence in unvaccinated adolescents in Ankara,
      Turkey.
AB  - The purpose of this study was to determine the age-specific rubella
      seroprevalence and factors associated with rubella seropositivity in unvaccinated
      adolescents in Ankara, Turkey. In this cross-sectional study 229 students were
      selected with stratified sampling methods in 2 primary and 2 high schools of low
      to medium socioeconomic status. Overall rubella seroprevalence was 92.6%. There
      was a significant association of rubella seropositivity with age and history of
      exanthema disease. Recommendations are made for vaccination of all children at
      age 1 year, combined with a one-time campaign of vaccination of adolescent girls
      and young women to provide future protection for those who are about to enter the
      child-bearing age.

PMID- 19161076
TI  - Allergic disease in 6--7-year-old schoolchildren in Urmia, Islamic Republic of
      Iran.
AB  - To determine the prevalence and risk factors of wheeze, eczema and rhinitis in 6-
      7-year-old schoolchildren in Urmia, the International Study of Asthma and
      Allergies in Childhood questionnaire was given to the parents of 2999 student.
      Prevalence rates for wheeze, rhinitis and eczema in the previous 12 months were
      9.4%, 9.8% and 2.7% respectively. The parents of only 12.8% of the children with
      current wheeze reported them as having asthma. The main risk factors for wheeze
      were male sex, presence of rhinitis or eczema, and smoking in the home.
      Prevalence of asthma and other allergic disease was lower than in industrialized
      countries and underdiagnosis of asthma was common.

PMID- 19161077
TI  - Prevalence and correlates of conduct disorder among inmates of juvenile detention
      centres, United Arab Emirates.
AB  - The prevalence of conduct disorder was assessed in 77 young people in 4 juvenile
      detention centres in the United Arab Emirates (UAE). The prevalence of conduct
      disorder was 24.7%, and recidivism, as indicated by repeat admissions to the
      centres, was found to be associated with conduct disorder. Having a diagnosis of
      conduct disorder was associated with a lower educational and occupational level
      of the father, as well as living with a single parent or relatives. Among UAE
      nationals, conduct disorder was also associated with having a mother who was a
      non-UAE national.

PMID- 19161078
TI  - Analysis of mental health research in the Islamic Republic of Iran over 3
      decades: a scientometric study.
AB  - This study described the characteristics of mental health research from the
      Islamic Republic of Iran published from 1973-2002. Research articles in
      psychiatry, psychology and neuroscience published in local or international
      journals were drawn from IranPsych, a national database of research in mental
      health and related disciplines. Of 3113 articles, 21.8% appeared in international
      journals, but there was international collaboration among the authors in only
      2.3%. There was a marked increase in the number of publications over time,
      especially in the last 5 years. Analysis of research areas showed a proportionate
      rise in neuroscience research and a decline in mental health service research.
      Our study provides an empirical basis for policy-making and strategy planning in
      the nation's mental health research.

PMID- 19161079
TI  - Cardiovascular disease risk factors, metabolic syndrome and obesity in an Iranian
      population.
AB  - As part of the Isfahan Healthy Heart Program, we evaluated the prevalence of
      cardiovascular disease risk factors in Iranians with generalized and abdominal
      obesity. We carried out a cross-sectional study on 3694 > or = 19 years. Overall,
      36.6% of men and 35.9% of women were overweight; 11.2% of men and 28.l% of women
      were obese. Mean body mass index (BMI), waist circumference (WC) and waist/hip
      ratio (WHR) increased with age up to 65 years. Total serum cholesterol,
      triglycerides and 2-hour post-load plasma glucose increased with BMI, WC and WHR
      in both sexes. Prevalence of metabolic syndrome was 19.8% in females with normal
      BMI, 48.1% in overweight females and 63.2% in obese females. In males,
      corresponding values were 3.7%, 18.0% and 40.1%.

PMID- 19161080
TI  - Clustering of coronary artery disease risk factors in patients with type 2
      diabetes and impaired glucose tolerance.
AB  - A cross-sectional study in Isfahan city, Islamic Republic of Iran, compared the
      frequency of coronary artery disease risk factors in known and newly diagnosed
      diabetic patients and individuals with impaired glucose tolerance (IGT) with
      normal individuals. The prevalence of known cases of diabetes, new cases of
      diabetes and cases with IGT in the general population sample of 3940 were 4.3%,
      1.1%, and 6.2% respectively. The frequency of dyslipidaemia was significantly
      different comparing diabetics and normal individuals. There was a significantly
      higher prevalence of risk factors (i.e. increased body mass index or waist
      circumference accompanied by dyslipidaemia) in the female population. The study
      highlights the importance of defining strategies for prevention and early
      diagnosis of diabetes in the community.

PMID- 19161081
TI  - [Diabetes and erectile dysfunction in Morocco: epidemiological study among
      outpatients].
AB  - We studied the relationship between erectile dysfunction (ED) and diabetes among
      189 men (> 40 years) attending primary health care centres in Morocco. Of the 89
      diabetic men, 82% had ED while only 17% of the 100 non-diabetic men had ED. The
      frequency of ED among diabetic men increased with age, from 60% in those aged 40
      49 years to 94.95% in those aged > or = 60 years (from 6.3% to 35.4% in men
      without diabetes for similar ages). ED was reported by 93.3% of diabetic men who
      had had diabetes for > 15 years. The frequency of ED did not differ with type of
      diabetes but it was significantly commoner in diabetic men with a low level of
      education and with hypertension.

PMID- 19161082
TI  - Profile of cancer family clustering in Jordan.
AB  - This paper explores cancer family clustering in a random sample of patients
      registered in the Jordan National Cancer Registry for the year 1999, the most
      recent year that complete data were available. A special instrument was designed
      and data collected through personal interviews. Of the final sample of 707 cancer
      patients, 23% had a positive family history of cancer, 59% of which was first
      degree clustering. For every proband there were 1.39 contacts. Half of them were
      first-degree relatives of the proband and 17% had cancer at the same site as the
      proband. Family clustering of cancer in Jordan appears to be of public health
      significance, and we recommend immediate and thorough followup of family members
      of cancer cases.

PMID- 19161083
TI  - Role of private laboratories in tuberculosis detection in Tehran, Islamic
      Republic of Iran.
AB  - To study the participation of the private sector in detection and diagnosis of
      tuberculosis, all suspected cases referring to 4 private laboratories in Tehran
      for acid-fast bacillus examination during 2002-03 were documented. Of 9037 cases
      enrolled in the study, 637 had positive examination results (7.1%). Of these 531
      (5.9%) cases were direct smear-positive and 489 (5.4%) were culture-positive.
      Data from the Iranian Ministry of Health showed 9479 cases referred to government
      laboratories in Tehran urban area during the study period, 208 (2.2%) of which
      were positive. This larger than expected proportion of TB patients who are
      detected and managed by the private sector indicates that much closer cooperation
      is needed between the public and private sectors.

PMID- 19161084
TI  - Use of the AMPLIFIED Mycobacterium tuberculosis direct test for the diagnosis of
      tuberculosis.
AB  - A comparative analysis was made of 3 conventional tests for tuberculosis (TB)
      versus a DNA probe technique among suspected TB patients at a reference centre in
      Greece. During 2004, we tested 2961 biological specimens from 2234 patients with
      the following methods: Ziehl-Neelsen staining, LowensteinOJensen culture, BACTEC
      mycobacteria growth indicator tubes (MGIT) and the Gen-Probe AMPLIFIED
      Mycobacterium tuberculosis direct test (MTD). Of a total of 136 TB patients
      diagnosed and under anti-TB treatment, 133 of them (98%) were positive by
      amplified MTD. There were 112 TB (82%) detected by the MGIT method, 102 (75%) by
      Lowenstein-Jensen culture and 75 (55%) by Ziehl-Neelsen staining. Using MTD the
      positive result is ready within hours compared with days or weeks.

PMID- 19161085
TI  - Knowledge, attitude and practices of Egyptian industrial and tourist workers
      towards HIV/AIDS.
AB  - This study explored knowledge, attitudes and practices towards HIV/AIDS infection
      among 1256 Egyptian industrial and tourism workers aged 16-40 years. Compared
      with industrial workers, tourism workers had a significantly better perception of
      the magnitude of the HIV/AIDS problem worldwide as well as in Egypt and of the
      likelihood of the problem worsening. Knowledge of tourism workers was also
      significantly better about causative agent of AIDS and methods of transmission.
      Both groups had negative attitudes towards patients living with HIV/AIDS
      concerning their right to confidentiality and to work. Both groups had a positive
      attitude towards behaviour change for protection from HIV/AIDS, principally via
      avoidance of extramarital sexual relations and adherence to religious beliefs.
      Use of condoms as a way to avoid HIV/AIDS was reported by only 0.4% of workers.

PMID- 19161086
TI  - Seroprevalence of HBV, HCV and HIV infection among intravenous drug users in
      Shahr-e-Kord, Islamic Republic of Iran.
AB  - This study was conducted in 2004 to evaluate the prevalence of hepatitis B (HBV),
      hepatitis C (HBC) and human immunodeficiency (HIV) virus infection in 133
      injecting drug users (IDUs) attending a voluntary rehabilitation centre in Shahr
      e-Kord, and to identify risk factors for these infections in this group. Serum
      samples were screened for HBV, HCV and HIV infection. Only 1 participant (0.8%)
      was HIV positive, 15 (11.2%) were HCV positive and 8 (6.0%) were positive for HBV
      surface antigen. There was significant correlation between using shared syringes
      and infection with HIV, HCV and HBV.

PMID- 19161087
TI  - Patient concerns regarding chronic hepatitis B and C infection.
AB  - Counselling of patients with viral hepatitis is often limited to discussions
      about how the virus is transmitted. The aim of the present study was to document
      the principal concerns of patients suffering from chronic hepatitis B and C
      infection. The most common volunteered concerns were infecting family members
      (80.6%), infecting others (66.7%), side-effects of treatment (50.0%), disease
      progression to cirrhosis (44.4%), loss of employment (41.7%), liver
      transplantation (36.1%), social stigma (36.1%), change in lifestyle (33.3%),
      development of liver cancer (25%), costs and money (22.2%), fear of disease
      (5.6%) and psychological disease (5.6%). Health care providers who focus
      counselling efforts exclusively on viral transmission are unlikely to address
      other important concerns.

PMID- 19161088
TI  - Prevalence of Chlamydia trachomatis infection in infertile women at a university
      hospital in Jordan.
AB  - In a prospective controlled study, we aimed to determine the prevalence of
      Chlamydia trachomatis infection in Jordanian women attending an infertility
      clinic and whether screening is useful as part of routine investigations for
      infertility. Two groups of patients (152 infertile patients and 146 control
      patients) had endocervical swab testing by polymerase chain reaction for the
      presence of C. trachomatis infection. A total of 6/152 patients in the
      infertility group tested positive for C. trachomatis (3.9%), compared with 1/146
      patients in the control group (0.7%), a difference that was not statistically
      significant. In view of the tendency toward increased prevalence of C.
      trachomatis infection, screening women for chlamydial infection as part of
      routine investigations for infertility is recommended.

PMID- 19161089
TI  - HLA antigens and inflammatory bowel disease in a sample of Iraqi patients.
AB  - This study investigated the association between HLA antigens and inflammatory
      bowel disease in 65 Iraqi patients (50 ulcerative colitis, 15 Crohn disease)
      compared with 67 matched controls. At HLA class I region, the patients showed
      significantly increased frequencies of A9 and B41 and a decrease of A11. Similar
      results were found when the clinical types were considered separately, except for
      A11, which was not significant. At HLA class II region, DR8 was significantly
      increased in the total patients, but the association was not maintained for
      ulcerative colitis or Crohn disease patients; instead Crohn disease was
      positively associated with DQ1. Comparing the clinical types revealed a
      significant difference in the antigen 816, suggesting that 816 is a
      differentiating marker in the disease.

PMID- 19161090
TI  - [Management of solid medical waste in the private medical sector in the occupied
      Palestinian territory: problems and remedial measures].
AB  - Management of solid medical waste in healthcare centres within the private sector
      in Palestine was studied. This included segregation, transport, treatment and
      final disposal. The study found that 30% of the centres completely segregated all
      kinds of healthcare waste, 35.9% segregated the sharps and 27.7% segregated
      infectious waste. Healthcare waste was manually transported in 99% of the centres
      that segregate waste. Nearly 87% of the centres disposed of the waste in open
      dumps randomly distributed in the area. It is concluded that all stages of
      healthcare waste management in healthcare centres in the private sector pose a
      hazard to personnel working in them and also to the general public in Palestine.

PMID- 19161091
TI  - Relationship between organizational climate and empowerment of nurses in
      Menoufiya hospitals, Egypt.
AB  - One factor influencing the outcome of care may be the nursing staffs experience
      of organizational work climate. We compared organizational climate and nurse's
      empowerment in specialty units at 2 hospitals in Egypt. Data were collected from
      164 diploma school staff nurses using 2 tools: the situational outlook
      questionnaire to assess organizational climate and the psychological empowerment
      in the workplace questionnaire. There was no statistically significant difference
      in the level of organizational climate between the 2 hospitals, which the
      majority of nurses classified as moderate. Most nurses reported a moderate level
      of empowerment in both hospitals and there was a statistically significant
      positive correlation between organizational climate and nurse's empowerment.

PMID- 19161092
TI  - Current status of dermatology residency training in Saudi Arabia: trainees'
      perspectives.
AB  - A cross-sectional survey was conducted to look at different aspects of
      dermatology residency programmes in Saudi Arabia from the residents' perspective.
      Self-administered questionnaires about future plans, academic activities,
      examinations, training, workload, surgical procedures, residents' rights and
      satisfaction were distributed to all 27 residents in all training centres during
      March-May 2004; 22 (81%) responded. The survey found that 50% of residents were
      not satisfied with their training and felt they were inadequately trained.
      Experience of performing certain procedures was much less than for residents in a
      similar study in the United States of America, and 50% of residents had not
      received any dermatologic surgery training. Moreover, 36% of residents had been
      verbally humiliated during their training.

PMID- 19161093
TI  - Teaching biostatistics and epidemiology in a postgraduate medical institution:
      are we going in the right direction?
AB  - We examined the attitude and knowledge of 40 supervisors and trainees as well as
      the impact of workshops on statistical thinking and analytical processes in a
      medical facility in Pakistan: 45% thought that statistics and epidemiology should
      be left to professional statisticians; 86% of the trainees and 58% of the
      supervisors, however, thought that statistics should be taught as a full-time
      subject. The majority of trainees (86%) were dissatisfied with the workshops
      compared to 33% of supervisors. Our findings indicate an urgent need to revise
      our approach to teaching statistics and epidemiology.

PMID- 19161094
TI  - Comparison of causes of headache diagnosed by neurologist and non-neurologist
      physicians, Babol, Islamic Republic of Iran.
AB  - Headache is a leading cause for consultation in many patients. We compared the
      agreement between non-neurologist physicians and neurologists in diagnosis of the
      cause of headache among 19,854 patients attending the neurology clinic of
      Yahyanejad Hospital, Babol, from 1995 to 2004, who were first diagnosed by the
      non-neurologist physician. The diagnoses of the neurologists were based on
      International Headache Society criteria. The commonest causes of headache
      diagnosed by the neurologist were tension-type and migraine, while sinusitis and
      ophthalmic disorders were the commonest diagnoses of the non-neurologist
      physicians. There is a need to inform physicians about the common causes of
      headache to ensure prompt and correct diagnosis.

PMID- 19161095
TI  - South Asian earthquake: psychiatric experience in a tertiary hospital.
AB  - In October 2005, northern Pakistan was devastated by an earthquake killing 73,000
      people. Some of the seriously injured were airlifted to a tertiary hospital in
      Rawalpindi, near Islamabad. This field report describes the psychiatric services
      delivered at that hospital. It explains how the needs were assessed and
      psychosocial interventions designed at different levels. The training needs of
      the medical staff were also identified and efforts were made to enhance their
      skills for psychosocial care. Finally, the report formulates some recommendations
      for improving such services.

PMID- 19161096
TI  - Inappropriate use of steroid and pneumocystis jiroveci pneumonia: report of two
      cases.

PMID- 19161097
TI  - Retained foreign body in the axillary region.

PMID- 19161098
TI  - Central retinal artery occlusion in a 28-year-old man after 10 days of smoking
      cessation.

PMID- 19161099
TI  - Epidemiological and cost analysis of multidrug-resistant tuberculosis in Oman.
AB  - We conducted an epidemiological and cost analysis for all 13 patients diagnosed
      with multaidrug-resistant tuberculosis (11 pulmonary, 2 extrapulmonary) in Oman
      from January 2000 to October 2005. The disease was secondary, or acquired, in 12
      of 13 patients. A total of 140 contacts were screened (mean 10.8 persons per
      patient), but contact tracing revealed no secondary cases. The mean number of
      drugs that TB isolates were resistant to was 2.8 (range 2-5). A mean of 4.7 drugs
      were given to patients, the mean length of therapy was 8 months and all patients
      were cured. The cost of medications for these multidrug-resistant cases was 14 to
      29 times higher than that for the standard drug-sensitive TB regimen.

PMID- 19161100
TI  - Prognostic value of infection and inflammation markers for late cardiac events in
      an Iranian sample.
AB  - We evaluated the serum levels of IgG antibodies to Helicobacter pylori, Chlamydia
      pneumoniae and cytomegalovirus and the level of the inflammatory markers C
      reactive protein and fibrinogen in 57 patients with acute coronary syndrome, 65
      with unstable angina, 60 with stable angina and 44 healthy controls, and whether
      these markers were associated with cardiac instability 6 months after admission.
      acute There was a significant increased risk of late coronary events (cardiac
      death or readmission with coronary events) associated with seropositivity to C.
      pneumoniae (adjusted odds ratio 2.12; 95% confidence interval: 1.16-4.08). Other
      parameters were not significantly associated with late cardiac events after
      adjustment for age, sex, diabetes mellitus, hypertension, hyperlipidaemia and
      smoking behaviour.

PMID- 19161101
TI  - Assessment of lung cancer risk due to exposure to radon from coastal sediments.
AB  - We conducted a lung cancer risk assessment for internal exposure to naturally
      occurring 222Rn gas both indoor and outdoor. A series of equations were used to
      estimate Rn concentrations indoor and outdoor and the associated lung cancer risk
      in some coastal regions in Egypt. The mean 222Rn concentrations were 42.98 (SD
      33.12) Bq/m3 and 8.63 (SD 6.16) Bq/m3 indoor and outdoor respectively. The mean
      risk of radon-induced cancer (deaths per million population) was 83.4 (SD 64.67)
      indoors and 25.1 (SD19.52) outdoors. Levels were higher for western regions of
      the country compared to eastern ones but the highest levels were in Rashid (Nile
      delta). Smoking was shown to increase the risk considerably.

PMID- 19161102
TI  - Evaluation of the Quit and Win contest for smoking cessation in the Islamic
      Republic of Iran.
AB  - Quit and Win is an international biannual smoking cessation contest. Although
      more than 70 countries participate, few are from the Eastern Mediterranean
      Region. This study evaluated 4 Quit and Win campaigns in Isfahan province,
      Islamic Republic of Iran, from 1998 to 2004, documenting participation rates,
      self-reported 1-month and 1-year abstinence rates and related factors.
      Participation rates among smokers ranged from 0.7%-2.4% of the smokers in
      Isfahan. One-month quit rates varied from 41.8% in 1998 to 92.8% in 2004. At 1
      year follow-up, self-reported quit rates varied from 22.5% in 1998 to 91.2% in
      2004. This model was found to be feasible and successful in our community, and
      can be implemented in other low- and middle-income countries.

PMID- 19161103
TI  - Patterns of tobacco use: results from the 2005 Global Youth Tobacco Survey in
      Lebanon.
AB  - We report the results of the 2005 Global Youth Tobacco Survey in Lebanon which
      investigated the self-reported attitudes and behaviours related to tobacco among
      3314 Lebanese schoolchildren aged 13-15 years. Current use of any tobacco product
      was 60.1%; the use of cigarettes was 10% and other tobacco products 59% with male
      predominance in all areas. About 80% of students lived in homes where others
      smoked. About 60% of current smokers wanted to quit smoking and 51% of all
      students had learned about the effects of tobacco in class. Over a quarter (27%)
      thought that boys who smoke have more friends and 17% believed that smoking makes
      boys more attractive. The majority of students had been exposed to both anti
      smoking media messages and pro-smoking advertisements.

PMID- 19161104
TI  - Smoking initiation among Iranian adolescents: a qualitative study.
AB  - In response to the need for effective tobacco prevention programmes in the
      Islamic Republic of Iran, the present study sought to determine the major risk
      factors for initiation of smoking by adolescents. A content analysis with a
      qualitative approach was conducted through 22 in-depth interviews, 2 focus groups
      (4 and 6 participants in each group) and 30 narratives. The following 3 themes
      emerged from the analysis as risk factors for initiating smoking by adolescents:
      personal factors, social factors and beliefs about smoking. Based on these
      findings, it is recommended that prevention activities should be embedded in a
      comprehensive approach which aims to change the smoking and parenting behaviour
      of parents and teachers, and at creating non-smoking policies in schools and
      other places where young people congregate.

PMID- 19161105
TI  - Changes in adrenal steroidogenesis in spontaneous bacterial peritonitis and
      sterile ascites.
AB  - Adrenal androgens, particularly dehydroepiandrosterone (DHEA), may have important
      regulatory effects on the immune system in humans. This study measured the
      changes in adrenal steroidogenesis in 13 non-infected cirrhosis patients with
      sterile ascites and 13 patients with spontaneous bacterial peritonitis and the
      relation with circulating interleukin-6 (IL-6) levels. Comparisons were made with
      10 healthy age-matched control subjects. The severity of bacterial peritonitis in
      liver cirrhosis was significantly associated with enhanced serum IL-6 and
      cortisol levels, and a decrease in serum DHEA sulfate in relation to serum IL-6
      concentrations. Careful, long-term studies on DHEA administered to cirrhosis
      patients are needed to assess its safety in improving a number of pathological
      conditions that complicate liver cirrhosis.

PMID- 19161106
TI  - Needs assessment and coping strategies of persons infected with HIV in Egypt.
AB  - The aims of this study were to identify the psychosocial and health care needs of
      persons living with HIV/AIDS and to determine their coping strategies. The study
      was conducted in 3 governorates of Egypt on 153 people infected with HIV. The
      data were collected using a structured questionnaire and in-depth interviews. The
      majority of the people had been forced to change the pattern of their sexual
      behaviour. Fear of stigmatization and feelings of anxiety, hopelessness and
      depression were frequently reported, resulting in a negative psychosocial impact
      on the infected person. Decreasing stigma and providing psycho-social support
      would help people living with HIV/AIDS to utilize effective ways of coping with
      the negative sequelae of the infection.

PMID- 19161107
TI  - Knowledge of and attitudes towards HIV/AIDS in Mashhad, Islamic Republic of Iran.
AB  - To assess knowledge and attitudes about HIV/AIDS in Mashhad, 960 people aged 13
      58 years who were approached in the street and agreed to participate completed an
      anonymous questionnaire. The mean of knowledge and attitudes scores were 9.8 (SD
      3.0) and 6.1 (SD 3.0) of a total 14 and 10 respectively. People with greater
      knowledge of HIV/AIDS had more positive attitudes to individuals with HIV/AIDS (P
      < 0.01). There were important misconceptions about HIV transmission such as
      through hugging, food, clothing, public places and insect bites. Regression
      analysis indicted that women had more tolerant attitudes than men (P < 0.01) and
      the more educated respondents had higher knowledge and attitudes scores (P <
      0.0001 and P < 0.001 respectively).

PMID- 19161108
TI  - Prevalence of genital Chlamydia in Iranian males with urethritis attending
      clinics in Mashhad.
AB  - Chlamydia trachomatis is a common cause of sexually transmitted disease which can
      cause severe consequences. Effective prevention requires knowledge of prevalence
      of infection in order to target interventions in a cost-effective manner. To
      determine the prevalence of chlamydial infection in Mashhad, northeastern Islamic
      Republic of Iran, this study was performed among male patients with urethritis.
      Urethral discharge was collected from 150 patients. Cell culture was established
      for diagnosis of Chlamydia in genital specimens. Cell culture showed that 9.3% of
      patients in this study were infected with Chlamydia. This study provides strong
      evidence that prevalence of Chlamydia in our region is quite high, which
      necessitates screening and treatment for the infection.

PMID- 19161109
TI  - Urologic diseases in the Islamic Republic of Iran: what are the public health
      priorities?
AB  - This study was designed to estimate the burden of urologic diseases in the
      Islamic Republic of Iran as a practical method for defining public health
      priorities. Using World Health Organization guidelines for national burden of
      disease studies, 6 steps were performed: selecting diseases to include; dynamic
      modelling of diseases; gathering data about urologic diseases; computing the
      local disability weights of urologic diseases; data analysis with DisMod II; and
      computing the disability-adjusted life years for each disease. Renal calculus,
      acute cystitis, chronic prostatitis, benign prostate hyperplasia, male
      infertility and adult polycystic kidney disease comprised the greatest burden.

PMID- 19161110
TI  - Oman Eye Study 2005: prevalence and determinants of glaucoma.
AB  - This community-based study was carried out to estimate the prevalence and
      identify the determinants of glaucoma in the Omani population in 2005-06.
      Residents of 75 randomly selected houses in 25 clusters participated in the
      survey. We interviewed and examined 3324 individuals aged > or = 30 years in
      their homes and in eye clinics to note personal details, glaucoma status and
      presence of selected risk factors: 180 were diagnosed as having glaucoma.
      Projected prevalence of glaucoma among the Omani population > or = 30 years was
      4.75%. Open angle and angle closure types of glaucoma contributed 40.6% and 37.8%
      respectively. History of hypertension was negatively, and older age and family
      history of glaucoma were positively, associated with glaucoma.

PMID- 19161111
TI  - Oman Eye Study 2005: validity of screening tests used in the glaucoma survey.
AB  - We carried out a validity assessment study for glaucoma screening procedures used
      during the survey conducted in Oman in 2005 on 6644 eyes in 3324 people > or = 30
      years. Ocular pressure and fundus changes were the screening parameters used:
      glaucoma was found in 433 eyes. Sensitivity for ocular pressure was 49.7% and
      specificity 95.6%. For optic disc changes, sensitivity was 48.4% and specificity
      97.9%. Combining both through parallel testing, sensitivity improved to 67.3% and
      specificity to 96.5%. An eye may, thus, be declared as not having glaucoma, but
      cannot be labelled as having glaucoma, using these parameters.

PMID- 19161112
TI  - Comparison of Perkins, Tono-Pen and Schiotz tonometers in paediatric patients
      under general anaesthesia.
AB  - This cross-sectional study aimed to investigate if the Tono-Pen, Schiotz and
      Perkins tonometers could be used interchangeably in general practice for
      measuring elevated intraocular pressure. A total of 74 eyes of 37 paediatric
      patients under general anaesthesia were checked with all 3 tonometers. All of the
      tonometers gave significantly different measurements from each other. However,
      with a mean difference of 1.4 mmHg and 95% limits of agreement of -5.7 to +8.6,
      the greatest agreement was between the Perkins and Tono-Pen tonometers. The
      Perkins tonometer is a hand-held variant of the Goldmann tonometer (the gold
      standard for intraocular pressure measures). Therefore the Tono-Pen with its ease
      of use and safety could be a reliable device for use in general practice.

PMID- 19161113
TI  - [Health-sector funding: options for funding health care in Iraq].
AB  - One of the basic issues faced by a state is the system of health care delivered
      to the citizens and method of funding this system. The importance of this issue
      lies in the fact that an established system of health care reflects the values,
      social priorities and economic system of such a state. This paper presents the
      available options for funding the health-care system in Iraq. It is a summary of
      ideas and views discussed on several occasions between 2004 and 2005, especially
      at the First National Conference on Health in Iraq, held in Baghdad in August
      2004, and the Health-Sector Funding Symposium, organized by the Ministry of
      Health in Amman, Jordan, in November 2004.

PMID- 19161114
TI  - [Evaluation of the maternal mortality surveillance system in public facilities in
      Tunisia (1999-2004)].
AB  - We report the performance indicators in 2004 of a follow-up on the system for
      recording maternal deaths which was established in 1999. The system was operating
      in 69.8% of public hospitals, and 96% of maternal deaths investigations were
      completed. In 69.8% of maternal deaths there was a direct obstetric cause.
      Haemorrhage was the major cause of maternal death (30.8%), followed by eclampsia
      (11%). The proportion of avoidable (certain or possible) deaths was 75.3%. There
      were problems in evaluation of risk presented by women and inadequate follow-up
      during the postpartum period and delay in appropriate treatment. Incomplete
      documentation and difficulty in ascertaining avoidability were problems faced by
      the regional follow-up committee.

PMID- 19161115
TI  - Optimal age of sexual maturation in Egyptian children.
AB  - To establish the optimal age of sexual maturation in Egyptian children, Tanner's
      maturity stages were determined for a sample of children and adolescents (1550
      girls, 1563 boys) ranging from 6.5 to 18.5 years. The mean age for attainment of
      pubic hair (stage PH2) was 10.46 (SD 1.36) years for girls and 11.86 (SD 1.45)
      years for boys. For axillary hair (stage A2), mean age was 11.65 (SD 1.62) years
      for girls and 13.55 (SD 1.52) years for boys. The mean age at menarche in girls
      was 12.44 years and for breast development (stage B2) was 10.71 (SD 1.30) years.
      Testicular volume by palpation showed that the mean age of genital stage G2 for
      boys was 10.56 (SD 1.40) years. The study results can aid in the assessment of
      sexual maturation and pubertal disorders in Egyptian adolescents.

PMID- 19161116
TI  - New growth charts for Libyan preschool children.
AB  - To draw up new growth charts for Libyan children under 5 years of age, a cross
      sectional survey was carried out in urban and rural areas in 2 regions of the
      Libyan Arab Jamahiriya from June 1999 to February 2000. Using WHO cluster
      sampling methodology, 1473 infants and children of both sexes aged between 0 and
      59 months were selected from residential areas, maternal and child health
      centres, kindergartens and the delivery section of hospitals. Growth charts for
      weight-for-age, height-for-age and weight-for-height were plotted and smoothed,
      to provide reference curves for clinical, epidemiological and research purposes.
      In addition, mean Z-scores were analysed by sociodemographic variables collected
      from interviews with parents. Factors with a strong influence on childhood growth
      patterns were child's age, mother's education level and sex.

PMID- 19161117
TI  - [Arabian food pyramid: unified framework for nutritional health messages].
AB  - There are several ways to present nutritional health messages, particularly
      pyramidic indices, but they have many deficiencies such as lack of agreement on a
      unified or clear methodology for food grouping and ignoring nutritional group
      inter-relation and integration. This causes confusion for health educators and
      target individuals. This paper presents an Arabian food pyramid that aims to
      unify the bases of nutritional health messages, bringing together the function,
      contents, source and nutritional group servings and indicating the inter-relation
      and integration of nutritional groups. This provides comprehensive, integrated,
      simple and flexible health messages.

PMID- 19161118
TI  - [Biological analysis of workers in the food sector in north Lebanon].
AB  - We investigated the prevalence of bacterial and parasitic infections among
      workers in a pastry factory in North Lebanon in 2004. We found 39% of the workers
      (n = 196) had nasal carriage of Staphylococcus aureus. Resistance of S. aureus
      isolates was 98.7% to penicillin G, 24.7% to fusidic acid, 14.3% to pefloxacine
      and tetracycline, 11.7% to erythromycin, 6.5% to oxacillin and amoxicillin
      clavulanate. Salmonella typhi was not found in any of the workers. Prevalence of
      intestinal parasites was 57.8% (n = 308). Amoebae comprised 72.5% (68.3%
      Entamoeba coli, 15.5% E. histolytica), followed by flagellates (18.0 %) (37.5%
      Dientamoeba fragilis, 31.3% Giardia lamblia) and nematodes (7.8%) (only Ascaris
      lumbricoides). The tuberculin test was positive in 16.3% of the workers (n =
      301).

PMID- 19161119
TI  - Intestinal parasitosis and use of untreated wastewater for agriculture in Settat,
      Morocco.
AB  - An evaluation was made of the risk of contamination by faecal parasites in the
      population from the use of wastewater in agriculture. The study was based in 3
      rural clusters in the northern region of Settat city, Morocco: 2 rural clusters
      exposed to untreated wastewater in agriculture and 1 not exposed. The sample
      comprised 333 people aged 3-60+ years: 214 exposed and 119 non-exposed. Stool
      samples were collected and examined for intestinal parasites. The results showed
      that the prevalence of intestinal parasitosis (i.e. evidence of at least 1 type
      of parasite) in the exposed group was significantly higher that the non-exposed
      group (66.4% versus 31.9%; relative risk 2.1). The household crowding index was
      also higher in the exposed group.

PMID- 19161120
TI  - Carrier detection of phenylketonuria in Iranian families by variable number
      tandem-repeat polymorphism analysis.
AB  - This study of Iranian families assessed the usefulness of carrier detection of
      phenylketonuria by variable number tandem-repeat (VNTR) polymorphism analysis. We
      studied 171 people (45 unrelated PKU subjects, and their parents and unaffected
      siblings). Of 342 chromosomes (131 non-PKU and 211 PKU), 5 VNTR alleles were
      identified. This VNTR system would yield a polymorphism information content of
      66%, comparable to that in Europeans and higher than in Chinese. Carrier
      detection by segregation analysis of VNTR was informative in 89.5% of siblings.
      We conclude that this polymorphism is highly informative in carrier detection of
      PKU in the Iranian population.

PMID- 19161121
TI  - Lower third molar eruption following orthodontic treatment.
AB  - This study assessed the effect of extraction and preservation of the 1st premolar
      on lower 3rd molar eruption. Orthodontic clinic records from 1993 to 1995 were
      evaluated before and after treatment and 8-9 years after treatment for 3 groups
      of patients: 32 with extraction of 1st premolars in both jaws, 32 with no
      extraction but orthodontic treatment and 48 controls with no extraction but
      orthodontic treatment in the upper jaws only. Successful eruption of 3rd molars
      was evaluated. There was a significant difference in the rates of successful
      eruptions in the extraction (42%), non-extraction (12%) and control (20%) groups.
      The findings indicate that 1st premolar extraction may increase the chance of 3rd
      molar eruption, leading to a lower incidence of health and economic
      complications.

PMID- 19161122
TI  - Suicide/homicide ratios in countries of the Eastern Mediterranean Region.
AB  - An analysis of suicide and homicide rates was made for countries of the Eastern
      Mediterranean Region using global burden disease data for 2000. The
      suicide/homicide ratio by age, sex and country level of income was calculated by
      dividing the suicide rate by the sum of the suicide and homicide rate. Males were
      more often victims of homicide whilst females were more often victims of suicide.
      For all male age groups except males 60+ years in high-income countries, the
      suicide/homicide ratio was 50% or less while for all female age groups except
      those 60+ years in high-income countries and females 5-14 years old in low- and
      middle-income countries, the suicide/homicide ratio was over 50%.

PMID- 19161123
TI  - Older adult care in Lebanon: towards stronger and sustainable reforms.
AB  - We assessed elderly care in Lebanon through direct observation and review of the
      literature and legislation with the aim of drawing attention to the current
      situation and the need for improvement, and providing suggestions to address the
      problems. The weaknesses of elderly care in Lebanon and obstacles to reform
      include the stigma of age, an inefficient health care system, a lack of geriatric
      specialists and social/volunteer services, and inadequacies in nursing homes.
      Countering the negative perception of ageing, promoting social welfare,
      refurbishing nursing homes and empowering volunteer services are needed to
      improve the lives and care of the elderly. Sustained initiatives by governmental
      agencies, physicians, volunteer services and the community are essential.
      Adequate funding is also imperative.

PMID- 19161124
TI  - Etiology of visual impairment in the United Arab Emirates: a hospital-based
      study.

PMID- 19161125
TI  - High-deductible health plans: litigation hazards for health insurers.

PMID- 19161126
TI  - Get sick, get out: the medical causes of home mortgage foreclosures.

PMID- 19161127
TI  - Never let your sense of morals keep you from doing what's right: using newly dead
      bodies as educational resources.

PMID- 19161128
TI  - Protecting the unborn as modern day eugenics.

PMID- 19161129
TI  - International outsourcing plus inexpensive, quality healthcare: binding
      arbitration makes this telemedical dream a reality.

PMID- 19161130
TI  - Kiss and make-up: a need for consolidation of FDA and cosmetic industry
      regulation programs.

PMID- 19161131
TI  - Ethical and legal issues accompanying legislation requiring HPV vaccination of
      girls.

PMID- 19161133
TI  - Improved residue function and reduced flow dependence in MR perfusion using least
      absolute-deviation regularization.
AB  - Cerebral blood flow (CBF) estimates derived from singular value decomposition
      (SVD) of time intensity curves from Gadolinium bolus perfusion-weighted imaging
      are known to underestimate CBF, especially at high flow rates. We report the
      development of a model-independent delay-invariant deconvolution technique using
      least-absolute-deviation (LAD) regularization to improve the CBF estimation
      accuracy. Computer simulations were performed to compare the accuracy of CBF
      estimates derived from LAD, reformulated SVD (rSVD) and standard SVD (sSVD)
      techniques. Simulations were performed at image signal-to-noise ratios ranging
      from 20 to 400, cerebral blood volumes from 1% to 10%, and CBF from 2.5 mL/100
      g/min to 176.5 mL/100 g/min to estimate the effect of these parameters on the
      accuracy of CBF estimation. The LAD method improved the CBF estimation accuracy
      by up to 32% in gray matter and 23% in white matter compared with rSVD and sSVD
      methods. LAD method also reduces the systematic bias of rSVD and sSVD methods to
      baseline SNR while producing more accurate and reproducible residue function
      calculation than either rSVD or sSVD method. Initial clinical implementation of
      the method on six representative clinical cases confirm the advantages of the LAD
      method over rSVD and sSVD methods.

PMID- 19161134
TI  - Mechanically adjustable coil array for wrist MRI.
AB  - In this work, the concept of mechanically adjustable MR receiver coil arrays is
      proposed and implemented for the specific case of human wrist imaging. An eight
      channel wrist array for proton MRI at 3 Tesla was constructed and evaluated. The
      array adjusts to the individual anatomy by a mechanism that fits a configuration
      of flexible coil elements closely around the wrist. With such adjustability, it
      is challenging to ensure robust electrical behavior and signal-to-noise (SNR)
      performance. These requirements are met by preamplifier decoupling and a suitable
      matching strategy based on pi networks that render the coil responses robust
      against changes in tuning, loading and mutual coupling. The robustness of the
      resulting SNR yield was studied by varying the effective coil matching over a
      wide range in a phantom imaging experiment. While SNR variation of up to 25% was
      observed at the surface of the phantom the SNR was essentially constant in the
      critical center region. A second SNR study in wrist phantoms of different sizes
      confirmed the benefits of bringing the coil elements very close, up to 3 mm, to
      the individual target volume. These findings were supported by initial in vivo
      imaging, exploiting high-sensitivity detection for highly resolved structural
      imaging.

PMID- 19161132
TI  - Phase-contrast magnetic resonance imaging measurements in intracranial aneurysms
      in vivo of flow patterns, velocity fields, and wall shear stress: comparison with
      computational fluid dynamics.
AB  - Evolution of intracranial aneurysms is known to be related to hemodynamic forces
      such as wall shear stress (WSS) and maximum shear stress (MSS). Estimation of
      these parameters can be performed using numerical simulations with computational
      fluid dynamics (CFD), but can also be directly measured with magnetic resonance
      imaging (MRI) using a time-dependent 3D phase-contrast sequence with encoding of
      each of the three components of the velocity vectors (7D-MRV). To study the
      accuracy of 7D-MRV in estimating these parameters in vivo, in comparison with
      CFD, 7D-MRV and patient-specific CFD modeling was performed for 3 patients who
      had intracranial aneurysms. Visual and quantitative analyses of the flow pattern
      and distribution of velocities, MSS, and WSS were performed using the two
      techniques. Spearman's coefficients of correlation between the two techniques
      were 0.56 for the velocity field, 0.48 for MSS, and 0.59 for WSS. Visual analysis
      and Bland-Altman plots showed good agreement for flow pattern and velocities but
      large discrepancies for MSS and WSS. These results indicate that 7D-MRV can be
      used in vivo to measure velocity flow fields and for estimating MSS and WSS.
      Currently, however, this method cannot accurately quantify the latter two
      parameters.

PMID- 19161135
TI  - Audiological and vestibular findings in the Kabuki syndrome.
AB  - Since the first description of Kabuki syndrome (KS) in 1981, over 350 cases from
      a variety of countries have been reported. Even though otolaryngological
      manifestations are common in KS, only a limited number of the reports provide
      audiological and vestibular data. The aim of the present study was to investigate
      the vestibular function and describe the audiological findings in KS. The present
      study reports no audiological and vestibular features in a group of 10 KS
      patients (7 males, 3 females), with chronological age ranging from 10 to 25 years
      (mean age = 14.5): a complete otoneurological and audiological work-up was
      performed for each patient and included where possible, the measurement of
      vestibular evoked potentials, caloric tests and static posturography. Hearing
      loss was found in 65% showing a mix or a conductive impairment; moreover the
      vestibular function was normal in 95% of the examined ears. In conclusion,
      audiological and vestibular examination should be considered when evaluating KS
      subjects.

PMID- 19161136
TI  - Hypogammaglobulinemia and Silver-Russell phenotype associated with partial
      trisomy 7q and partial monosomy 21q.

PMID- 19161138
TI  - Mutation analysis of the myocyte enhancer factor 2A gene (MEF2A) in patients with
      left ventricular hypertrophy/hypertrophic cardiomyopathy.

PMID- 19161137
TI  - Mutation in the COCH gene is associated with superior semicircular canal
      dehiscence.

PMID- 19161139
TI  - Familial 14.5 Mb interstitial deletion 13q21.1-13q21.33: clinical and array-CGH
      study of a benign phenotype in a three-generation family.
AB  - We report on the clinical and cytogenetic findings as well as the array-based
      characterization of an interstitial familial 13q21 deletion initially recognized
      by standard karyotyping. Although 13q deletions are known to imply a wide
      variability of clinical consequences, the deletion carriers of the familial
      deletion in three generations did not reveal a relevant phenotype. The
      breakpoints and the deletion size in all three carrier individuals were
      determined by molecular karyotyping confirming a large 14.5 Mb deletion
      encompassing the 13q21.1-13q21.33 region identical in all three carriers. Gene
      paucity and the lack of dosage-sensitive genes in the delineated region might
      explain the apparently innocuous nature of this chromosomal anomaly. The example
      of this family presents evidence for describing the chromosomal region 13q21.1
      13q21.33 as a large euchromatic variant or benign copy number variation without
      phenotypic consequences. Our data underline the importance of a phenogenetic
      approach combining clinical and laboratory evidence in the interpretation of
      segmental chromosomal anomalies especially in genetic counseling related to
      prenatal diagnosis.

PMID- 19161140
TI  - A partial trisomy 1q patient with a deletion 1q22 and an insertion 1(q42q44) into
      1q22.

PMID- 19161141
TI  - Further clinical delineation of the Borjeson-Forssman-Lehmann syndrome in
      patients with PHF6 mutations.
AB  - Borjeson-Forssman-Lehmann syndrome is an X-linked condition caused by PHF6
      mutations. The classical description of males with this disorder includes severe
      intellectual disability with epilepsy, microcephaly, short stature, obesity,
      hypogonadism, and gynecomastia. We present three males with PHF6 mutations whose
      features included deep-set eyes, large ears, coarse face, tapering fingers, and
      truncal obesity. Unlike the original description of the syndrome; however, the
      males described herein had varying degrees of intellectual disability and
      hypogonadism, were of normal to tall stature, had normal to large head sizes, and
      did not have seizures. This departure from the usual clinical description of
      Borjeson-Forssman-Lehmann syndrome is consistent with recent reports of males
      with mutations in PHF6. In addition, we describe the phenotype and X-inactivation
      pattern in two females heterozygous for PHF6 mutations, both of whom have mild
      features of the syndrome.

PMID- 19161142
TI  - Identification of sex chromosome mosaicism: is analysis of 20 metaphase cells
      sufficient?

PMID- 19161143
TI  - Anterior segment anomalies of the eye, growth retardation associated with
      hypoplastic pituitary gland and endocrine abnormalities: Jung syndrome or a new
      syndrome?
AB  - We report on two children from an inbred Arab family with anterior segment
      anomalies of the eyes, growth retardation, associated with small pituitary gland,
      and endocrine abnormalities. The features in the sibs in this report are similar
      to those described in Peters-plus syndrome. However, small pituitary gland
      associated with growth hormone deficiency has not been reported in Peters-plus
      syndrome. In addition, sequencing of the B3GALTL gene, the gene implicated in
      Peters-plus syndrome did not reveal any mutation in the sibs reported here. The
      association of anterior segment anomalies of the eye, growth retardation, and
      endocrine problems has previously been described by Jung et al. in 1995. We
      suggest that the features in the children in this report could represent variable
      manifestation of this syndrome or previously not described syndrome.

PMID- 19161144
TI  - Comparison of gradient encoding directions for higher order tensor diffusion
      data.
AB  - Recently, higher order tensors were proposed for a more advanced representation
      of non-Gaussian diffusion. These advanced diffusion models have new requirements
      for the gradient encoding schemes used in the diffusion weighted image
      acquisition. The influence of the gradient encoding schemes on the estimated
      standard second order diffusion tensor was previously investigated. Here, we
      focus on the suitability of different encoding scheme types for higher order
      tensor models. Two quality measures for the gradient encoding schemes, the
      condition number of the estimation matrix and a new measure that evaluates the
      signal deviation on simulated data, are used to determine which gradient encoding
      is suited best for higher order tensor estimations. Six different gradient
      encoding scheme types were investigated. A certain force-minimizing scheme type
      gave the best results in the evaluations presented here.

PMID- 19161145
TI  - Intra-thoracic blood volume measurement by contrast magnetic resonance imaging.
AB  - The intra-thoracic blood volume (ITBV) is a cardiovascular parameter related to
      the cardiac preload and left ventricular function. Its assessment is, therefore,
      important for diagnosis and follow-up of several cardiovascular dysfunctions.
      Nowadays, the ITBV can be accurately measured only by invasive indicator dilution
      techniques, which require a double catheterization of the patient. In this study,
      a novel technique is presented for ITBV assessment by dynamic magnetic resonance
      imaging after intravenous injection of a small bolus of gadolinium chelate. The
      dose was chosen on the basis of in vitro calibration. The bolus first pass is
      detected from a simultaneous dynamic image series of the right and left
      ventricles. Two indicator dilution curves are derived and used to inspect the
      transpulmonary dilution system. Various mathematical models for the
      interpretation of the measured indicator dilution curves are compared. The ITBV
      is assessed as the product of the transpulmonary mean transit time of the
      indicator and the cardiac output, obtained by phase contrast magnetic resonance
      angiography. In vitro measurements showed a correlation coefficient larger than
      0.99 and preliminary tests with volunteers proved the feasibility of the method,
      opening new possibilities for noninvasive quantitative cardiovascular
      diagnostics.

PMID- 19161147
TI  - Recessive developmental delay, small stature, microcephaly and brain
      calcifications with locus on chromosome 2.
AB  - Two interrelated Omani families are described with eight children manifesting a
      genetic disorder with widespread brain calcifications. Brain imaging showed
      extensive scattered calcifications of basal ganglia and cortex, suggesting
      possible Aicardi-Goutieres syndrome (AGS) or Coats' Plus syndrome. However, the
      clinical features in the present families diverge substantially from these two
      conditions. Growth delay, mild developmental delay, and poor school performance
      were present in all affected individuals, but progressive deterioration of
      neurological function was not apparent, nor were there significant cortical
      whitematter disease or retinopathy. Genome-wide linkage and fine-mapping analyses
      of the extended family members and affected individuals indicate a genetic locus
      for this disorder on Chromosome 2 with a LOD score of 6.17. The Chromosome 2
      locus is novel and the clinical presentation displays features distinguishing the
      condition from either Coats' or AGS, making this a new variant or possibly a new
      disorder of inherited brain calcification.

PMID- 19161148
TI  - Cervical vertebrae, cranial base, and mandibular retrognathia in human triploid
      fetuses.
AB  - On profile radiographs of adults, an association between fusions of cervical
      vertebrae, deviations in the cranial base and mandibular retrognathia has been
      documented radiographically. An elaboration of this association on a histological
      level is needed. In human triploid fetuses severe mandibular retrognathia and
      deviations in the cranial base have previously been described radiographically
      (without cephalometry) and cervical column fusions radiographically as well as
      histologically. Therefore, triploid fetuses were chosen to elucidate the cranial
      base cephalomterically and histologically. In the present study, eight triploid
      fetuses were analyzed radiographically and histologically focusing especially on
      the cranial base, which borders to the spine and to which the jaws are attached.
      A histological analysis of the cranial base has not previously been performed in
      triploid cases. An enlarged cranial base angle and a retrognathic position of the
      mandible were documented cephalometrically on radiographs of all cases.
      Histologically, malformations were observed in the cranial base as well as in the
      spine. These are new findings indicating the association between the occipital
      bone and the uppermost vertebra in the body axis. As the notochord connects the
      cervical column and the cranial base in early prenatal life, molecular signaling
      from the notochord may in future studies support the notochord as the
      developmental link between abnormal development in the spine and the cranial
      base.

PMID- 19161149
TI  - CLOVE(S) syndrome: expanding the acronym.

PMID- 19161150
TI  - Assessing the understanding of biobank participants.
AB  - Biobanks have been developed as a tool to better understand the genetic basis of
      disease by linking DNA samples to corresponding medical information. The broad
      scope of such projects presents a challenge to informed consent and participant
      understanding. To address this, 200 telephone interviews were conducted with
      participants in the NUgene Project, Northwestern University's biobank. Interviews
      included a modified version of the "quality of informed consent measure" (QuIC)
      and semi-structured questions which were analyzed thematically for 109 of the
      interviews. The QuIC, originally applied to cancer clinical trials, objectively
      assessed some of the components of informed consent for a biobank, and interview
      questions provided rich data to assist in interpreting participant understanding.
      The best understood domains included: the nature of the study, benefit to future
      patients, and the voluntary nature of participation. Lower knowledge scores
      included: potential risks and discomforts, experimental nature of the research,
      procedures in the event of study-related injury, and confidentiality issues.
      Qualitatively, confidentiality protections of the study were described as good by
      most (>50%). Although some cited concerns with employer (12%) or insurance
      discrimination (25%), most considered the risks to privacy low (25%) or none
      (approximately 60%). Only 10% of participants explicitly stated they had no
      expectation for personal benefit, and when asked whether they expected to be
      contacted with study results, respondents were split between having no
      expectation (39%), being hopeful for results (37%) and expecting to be contacted
      with results (12%). These findings are informative to those establishing and
      implementing biobanks, and to the IRBs reviewing such studies.

PMID- 19161151
TI  - Interstitial deletion 2p11.2-p12: report of a patient with mental retardation and
      review of the literature.
AB  - Deletions of chromosome bands 2p11.2 and 2p12 are rare, and only six patients
      have been reported to date. Here, we report on a 5-year-old girl with an 11.4 Mb
      interstitial deletion of chromosome bands 2p11.2-p12 and the characterization of
      this deletion by high-resolution array CGH. The patient presented with mental
      retardation, microcephaly and short stature. Facial features included broad nasal
      bridge, frontal bossing and mild dolichocephaly. Phenotypic comparison with
      previously published patients failed to reveal a consistent clinical pattern
      apart from developmental delay/mental retardation, which is probably due to
      different sizes and/or positions of the individual deletions. Among the 40 known
      genes deleted in our patient is REEP1, haploinsufficiency of which causes
      autosomal dominant spastic paraplegia type 31 (SPG31, OMIM 610250). Additional
      patients with well-characterized deletions within 2p11.2 and 2p12 will be needed
      to determine the role of individual genes for the clinical manifestations.

PMID- 19161152
TI  - Detection of 53 FBN1 mutations (41 novel and 12 recurrent) and genotype-phenotype
      correlations in 113 unrelated probands referred with Marfan syndrome, or a
      related fibrillinopathy.
AB  - Mutations in the gene encoding fibrillin 1 (FBN1) cause Marfan syndrome (MFS),
      and related connective tissue disorders. The disease spectrum is wide and while
      many genotype-phenotype correlations have been reported, few have been
      consistent. In this study FBN1 was analyzed in 113 patients with MFS or Marfan
      like features. Fifty-three mutations were identified in 52 individuals, 41 of
      which were novel. The mutations comprised 26 missense, 11 splice site, 7
      frameshift, 6 nonsense, 1 in-frame deletion, and 2 whole exon deletions. In
      common with previous studies, genotype-phenotype analysis showed that a FBN1
      mutation was more likely to be identified in patients fulfilling Ghent criteria
      (P = 0.005) and in those who had ectopia lentis (EL) (P < 0.0001). Other
      previously reported genotype-phenotype correlations were also considered and a
      new inverse association between a mutation in exons 59-65, and EL emerged (P =
      0.002).

PMID- 19161153
TI  - Autosomal dominant inheritance of cardiac valves anomalies in two families:
      extended spectrum of left-ventricular outflow tract obstruction.
AB  - Only a limited number of families with clear monogenic inheritance of
      nonsyndromic forms of congenital valve defects have been described. We describe
      two multiplex pedigrees with a similar nonsyndromic form of heart valve anomalies
      that segregate as an autosomal dominant condition. The first family is a three
      generation pedigree with 10 family members affected with congenital defects of
      the cardiac valves, including six patients with aortic stenosis and/or aortic
      regurgitation. Pulmonary and/or tricuspid valve abnormalities were present in
      three patients, and ventricular septal defect (VSD) was present in two patients.
      The second family consists of 11 patients in three generations with aortic valve
      stenosis in seven patients, defects of the pulmonary valves in two patients, and
      atrial septal defect (ASD) in two patients. Incomplete penetrance was observed in
      both families. Although left-ventricular outflow tract obstruction was present in
      most family members, the co-occurrence with pulmonary valve abnormalities and
      septal defects in both families is uncommon. These families provide evidence that
      left-sided obstructive defects and thoracic aortic aneurysm may be accompanied by
      right-sided defects, and even septal defects. These families might be
      instrumental in identifying genes involved in cardiac valve morphogenesis and
      malformation.

PMID- 19161154
TI  - Molecular cytogenetic characterization of a 4p15.1-pter duplication and a 4q35.1
      qter deletion in a recombinant of chromosome 4 pericentric inversion.
AB  - To date, 10 cases of recombinant of chromosome 4 pericentric inversion involving
      sub-bands p14p15 and q35 have been described. We report on the first case
      analyzed using array-CGH in a female infant presenting psychomotor and growth
      retardation, facial anomalies, axial hypotonia, short neck, wide spaced nipples
      and cardiac defects. Conventional karyotype associated to FISH revealed a
      recombinant chromosome 4 with partial 4p duplication and 4q deletion derived from
      a paternal pericentric inversion. Array-CGH allowed us to precise rec4
      breakpoints: the proposita carried a small 4.82-4.97 Mb 4q35.1 terminal deletion
      and a large 35.3-36.7 Mb 4p15.1 terminal duplication. Duplications of the distal
      2/3 of short arm of chromosome 4 give rise to recognizable craniofacial features
      but no specific visceral malformation. A contrario small terminal 4q deletions
      are associated with cardiac defects. This case and review of literature suggest
      that two genes ArgBP2 and PDLIM3, located at 4q35.1 and both involved in cardiac
      and muscle development, could be responsible for cardiac defects observed in
      terminal 4q35.1 deletions.

PMID- 19161155
TI  - Mesiodens, a new microform of holoprosencephaly?

PMID- 19161156
TI  - A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of
      Rett syndrome.
AB  - Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost
      exclusively in female subjects, have been recently found to be the cause of a
      phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We
      describe the first CDKL5 mutation detected in a male individual with 47,XXY
      karyotype. This previously unreported, de novo, mutation truncates the large
      CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular
      localization of the CDKL5 protein. The resulting phenotype is characterized by a
      severe early-onset epileptic encephalopathy, global developmental delay, and
      profound intellectual and motor impairment with features reminiscent of Rett
      syndrome. In light of the data presented we discuss the possible phenotypic
      modulatory effects of the supernumerary wild type X allele and pattern of X
      chromosome inactivation and stress the importance of considering the causal
      involvement of CDKL5 in developmentally delayed males with early-onset seizures.

PMID- 19161157
TI  - Further delineation of the critical region for the 9p-duplication syndrome.

PMID- 19161158
TI  - Use of antihistamine medications during early pregnancy and isolated major
      malformations.
AB  - BACKGROUND: Antihistamines are commonly used during pregnancy. There is little
      evidence that they have teratogenic effects, but there are knowledge gaps with
      respect to newer products, as well as the relationship between specific
      antihistamines and specific birth defects. METHODS: Using the National Birth
      Defects Prevention Study (1997-2003), the authors examined associations between
      maternal use of 14 antihistamines during early pregnancy and 26 isolated major
      birth defects. A Bayesian analysis incorporating prior knowledge about the
      relationships between antihistamines, birth defects, and measured covariates was
      conducted. RESULTS: Of the 364 associations investigated, 24 had 95% posterior
      intervals excluding 1.0. All 24 associations were positive; 23 associations were
      of weak to moderate magnitude (posterior OR < 3.0) and one was strong (OR > 6.0)
      but very imprecise. Of the 24 associations, 20 were with noncardiac defects.
      Eight associations involved the antihistamine diphenhydramine. CONCLUSIONS: The
      results of this study generally were consistent with no association between birth
      defects and antihistamine use during early pregnancy. Several of the findings
      might warrant further investigation, although the observed elevated associations
      should be interpreted in the context of the number of associations investigated
      and the analysis of retrospective, self-reported data.

PMID- 19161159
TI  - The oxidative stress response is region specific in organogenesis stage mouse
      embryos exposed to 5-bromo-2'-deoxyuridine.
AB  - BACKGROUND: The exposure of mouse embryos to 5-bromo-2'-deoxyuridine (BrdU), a
      model teratogen, generates oxidative stress, induces c-Fos dependent activator
      protein-1 (AP-1) DNA binding activity, and causes skeletal malformations (Sahambi
      and Hales, 2006). The goal of this study was to test the hypothesis that the
      ability of BrdU to induce oxidative stress, rather than its incorporation into
      DNA per se, is responsible for triggering the ensuing malformations. To test this
      hypothesis, we examined the regional localization of BrdU incorporation, 8
      oxoguanine (8-oxoG), a marker of oxidative stress, and c-Fos immunoreactivity in
      organogenesis stage mouse embryos exposed to a teratogenic dose of BrdU. METHODS:
      Timed pregnant CD1 mice received vehicle (saline) or BrdU (600 or 1000 mg/kg body
      weight) on gestation day 9. N-acetyl-L-cysteine, a glutathione precursor, was
      administered to GD 9 mice 2 hours before treatment with vehicle or BrdU to
      determine the impact of inhibiting the oxidative stress response. Embryos were
      excised 3 hours after BrdU treatment and processed for staining for BrdU
      incorporated into DNA, 8-oxoG, and c-Fos. RESULTS: BrdU incorporation, 8-oxoG
      adduct formation and c-Fos immunoreactivity were highest in the rostral and
      caudal developing tissues of BrdU-exposed embryos. Although preadministration of
      N-acetyl-L-cysteine at a dose that decreased BrdU teratogenicity dampened the
      oxidative stress response, it did not affect the incorporation of BrdU into DNA.
      CONCLUSIONS: These data show that rostral and caudal neuroepithelial cells are
      particularly susceptible to oxidative stress in the organogenesis-stage embryo.

PMID- 19161160
TI  - An association study of 45 folate-related genes in spina bifida: Involvement of
      cubilin (CUBN) and tRNA aspartic acid methyltransferase 1 (TRDMT1).
AB  - BACKGROUND: Spina bifida is a class of neural tube defects, which are congenital
      malformations of the central nervous system with a prevalence of 0.5 to 12 per
      1000 births globally. In this article we attempt to identify genes related to
      folate and its metabolic pathways that are involved in the etiology of spina
      bifida. METHODS: We selected 50 folate metabolism-related genes and genotyped
      polymorphisms in those genes. Eighty-seven polymorphisms in 45 genes passed
      quality controls. Associations with spina bifida were investigated in 180
      patients and 190 controls. For those polymorphisms that were nominally associated
      with spina bifida risk, the relation with serum and red blood cell folate,
      vitamin B(12), and homocysteine was evaluated in controls. RESULTS: A
      polymorphism in CUBN was significantly associated with decreased spina bifida
      risk, after correction for multiple testing, and was related to increased vitamin
      B(12) (p = 0.039) and red blood cell folate (p = 0.001). The CUBN gene encodes
      the intrinsic factor-cobalamin receptor (or cubilin), a peripheral membrane
      protein that acts as a receptor for intrinsic factor-vitamin B(12) complexes.
      Vitamin B(12) is an important cofactor in the folate metabolism, and low B(12)
      status in mothers has been linked to neural tube defects in children. Other
      interesting findings include nominally significant associations with
      polymorphisms in TRDMT1, ALDH1L1, SARDH, and SLCA19A1 (RFC1). CONCLUSION: Our
      study indicates interesting new candidate genes and functional pathways for
      further study and confirms earlier findings. None of the genes CUBN, TRDMT1,
      ALDH1L1, or SARDH have been investigated previously for association with spina
      bifida.

PMID- 19161161
TI  - Bladder exstrophy-epispadias complex.
AB  - The bladder exstrophy-epispadias complex (BEEC) represents an anterior midline
      defect with variable expression comprising a spectrum of anomalies involving the
      abdominal wall, pelvis, urinary tract, genitalia, and occasionally the spine and
      anus. The vast majority of BEEC cases are classified as non-syndromic and the
      etiology of this malformation is still unknown. This review presents the current
      state of knowledge on this multifactorial disorder, including historical
      retrospect, phenotypic and anatomical characterization, epidemiology, proposed
      developmental mechanisms, existing animal models, and implicated genetic and
      environmental components. These published lines of evidence argue strongly that
      BEEC occurs as a result of strong genetic predisposition that is yet to be
      deciphered.

PMID- 19161162
TI  - Periconceptional folic acid and multivitamin supplementation for the prevention
      of neural tube defects and other congenital abnormalities.
AB  - The pioneering studies of Smithells et al. showed the reduction of recurrent
      neural-tube defects (NTD) after periconceptional folic acid-containing
      multivitamin supplementation. The Hungarian Periconceptional Service was
      established in 1984, and this primary health care system offered a chance to
      organize a randomized controlled trial to check whether the supplementation of a
      multivitamin containing 0.8 mg of folic acid during the periconceptional period
      is appropriate for the reduction of a first occurrence of NTD in the family. This
      found a reduction of approximately 90% of primary NTD. An unexpected finding was
      a significant reduction in the rate of congenital abnormalities overall: 20.6 per
      1000 in the 'multivitamin' group, and 40.6 per 1000 in the 'trace-element-like'
      placebo group (RR = 0.53, 95% CI: 0.35-0.70). When the 6 cases of NTD were
      excluded, this difference in the rates of major congenital abnormalities between
      the two study-groups remained very highly significant (p < 0.0001).
      Cardiovascular malformations and urinary tract defects were particularly
      affected. These findings were confirmed in the Hungarian cohort-controlled trial
      and by observational studies in other countries. Two questions remain to be
      answered. Is folic acid better alone or with multivitamins? What is the optimal
      dose of folic acid? Overall, the Hungarian experiences of periconceptional care
      have shown not only primary prevention of several severe congenital abnormalities
      but also a good cost-benefit balance.

PMID- 19161163
TI  - Geodesic topological analysis of trabecular bone microarchitecture from high
      spatial resolution magnetic resonance images.
AB  - In vivo assessment of trabecular bone microarchitecture could improve the
      prediction of fracture risk and the efficacy of osteoporosis treatment and
      prevention. Geodesic topological analysis (GTA) is introduced as a novel
      technique to quantify the trabecular bone microarchitecture from high-spatial
      resolution magnetic resonance (MR) images. Trabecular bone parameters that
      quantify the scale, topology, and anisotropy of the trabecular bone network in
      terms of its junctions are the result of GTA. The reproducibility of GTA was
      tested with in vivo images of human distal tibiae and radii (n = 6) at 1.5 Tesla;
      and its ability to discriminate between subjects with and without vertebral
      fracture was assessed with ex vivo images of human calcanei at 1.5 and 3.0 Tesla
      (n = 30). GTA parameters yielded an average reproducibility of 4.8%, and their
      individual areas under the curve (AUC) of the receiver operating characteristic
      curve analysis for fracture discrimination performed better at 3.0 than at 1.5
      Tesla reaching values of up to 0.78 (p < 0.001). Logistic regression analysis
      demonstrated that fracture discrimination was improved by combining GTA
      parameters, and that GTA combined with bone mineral density (BMD) allow for
      better discrimination than BMD alone (AUC = 0.95; p < 0.001). Results indicate
      that GTA can substantially contribute in studies of osteoporosis involving
      imaging of the trabecular bone microarchitecture.

PMID- 19161164
TI  - Gradient moment compensated magnetic resonance spectroscopic imaging.
AB  - Spectroscopic imaging applications outside of the brain can suffer from artifacts
      due to inherent long scan times and susceptibility to motion. A fast
      spectroscopic imaging sequence has been devised with reduced sensitivity to
      motion. The sequence uses oscillating readout gradients and acquires k-space data
      in a spiral out-in fashion, which allows fast k-space coverage. We show that a
      spiral out-in readout acquisition is characterized by small gradient moments,
      reducing sensitivity to motion-induced artifacts. Data are acquired comparing the
      sequence to normal phase encoded spectroscopic imaging and conventional spiral
      spectroscopic imaging protocols. In addition, in vivo data are acquired from the
      liver, demonstrating potential usage as a multivoxel fat/water spectroscopic
      imaging tool. Results indicate that in the presence of motion, ghosting effects
      are reduced while metabolite signal increases of approximately 10% can be
      achieved.

PMID- 19161165
TI  - B1 and T1 insensitive water and lipid suppression using optimized multiple
      frequency-selective preparation pulses for whole-brain 1H spectroscopic imaging
      at 3T.
AB  - A new method for the simultaneous suppression of water and lipid resonances using
      a series of dual-band frequency-selective radiofrequency (RF) pulses with
      associated dephasing gradients is presented. By optimizing the nutation angles of
      the individual pulses, the water and lipid suppression is made insensitive to a
      range of both T1-relaxation times and B1 inhomogeneities. The method consists
      only of preparatory RF pulses and thus can be combined with a wide variety of
      MRSI schemes including both long and short TE studies. Simulations yield
      suppression factors, in the presence of +/-20% B1 inhomogeneity, on the order of
      100 for lipid peaks with three different T1s (300 ms, 310 ms, and 360 ms), and
      water peaks with T1s ranging from 0.8 s to 4 s. Excellent in vivo study
      performance is demonstrated using a 3 Tesla volumetric proton spectroscopic
      imaging (1H-MRSI) sequence for measuring the primary brain metabolites peaks of
      choline (Cho), creatine (Cr), and N-acetyl aspartate (NAA).

PMID- 19161166
TI  - Quantitative assessment of DTI-based muscle fiber tracking and optimal tracking
      parameters.
AB  - Diffusion tensor imaging-based fiber tracking in skeletal muscle has been used to
      reconstruct and quantify muscle architecture. In addition, the consistent pattern
      of muscle fiber geometry enables a quantitative assessment of the fiber tracking.
      This work describes a method to determine the accuracy of individual muscle fiber
      tracts based on the location at which the fibers terminate, the fiber path, and
      similarity to the neighboring fibers. In addition, the effect of different stop
      criteria settings on this quantitative assessment was investigated. Fiber
      tracking was performed on the tibialis anterior muscle of nine healthy subjects.
      Complete fiber tracts covered 89.4 +/- 9.6% and 75.0 +/- 15.2% of the aponeurosis
      area in the superficial and deep compartments, respectively. Applications of the
      method include the exclusion of erroneous fiber-tracking results, quantitative
      assessment of data set quality, and the assessment of fiber-tracking stop
      criteria.

PMID- 19161167
TI  - Effect of inflow of fresh blood on vascular-space-occupancy (VASO) contrast.
AB  - In vascular-space-occupancy (VASO)-MRI, cerebral blood volume (CBV)-weighted
      contrast is generated by applying a nonselective inversion pulse followed by
      imaging when blood water magnetization is zero. An uncertainty in VASO relates to
      the completeness of blood water nulling. Specifically, radio frequency (RF) coils
      produce a finite inversion volume, rendering the possibility of fresh, non-nulled
      blood. Here, VASO-functional MRI (fMRI) was performed for varying inversion
      volume and TR using body coil RF transmission. For thin inversion volume
      thickness (delta(tot) < 10 mm), VASO signal changes were positive (DeltaS/S = 2.1
      2.6%). Signal changes were negative and varied in magnitude for intermediate
      inversion volumes (delta(tot) = 100-300 mm), yet did not differ significantly (P
      > 0.05) for delta(tot) > 300 mm. These data suggest that blood water is in steady
      state for delta(tot) > 300 mm. In this appropriate range, long-TR VASO data
      converged to a less negative value (DeltaS/S = -1.4% +/- 0.2%) than short-TR data
      (DeltaS/S = -2.2% +/- 0.2%), implying that cerebral blood flow or transit-state
      effects may influence VASO contrast at short TR.

PMID- 19161168
TI  - Magnetic field correlation as a measure of iron-generated magnetic field
      inhomogeneities in the brain.
AB  - The magnetic field correlation (MFC) at an applied field level of 3 Tesla was
      estimated by means of MRI in several brain regions for 21 healthy human adults
      and 1 subject with aceruloplasminemia. For healthy subjects, highly elevated MFC
      values compared with surrounding tissues were found within the basal ganglia.
      These are argued as being primarily the result of microscopic magnetic field
      inhomogeneities generated by nonheme brain iron. The MFC in the
      aceruloplasminemia subject was significantly higher than for healthy adults in
      the globus pallidus, thalamus and frontal white matter, consistent with the known
      increased brain iron concentration associated with this disease.

PMID- 19161169
TI  - Nonlinear DeltaR*2 effects in perfusion quantification using bolus-tracking MRI.
AB  - Dynamic susceptibility contrast MRI involves injection of a contrast agent, whose
      concentration is estimated from DeltaR*2 changes. However, measurement of
      contrast-agent concentration is prone to various sources of error; in particular,
      the commonly assumed linear relationship between contrast agent concentration and
      DeltaR*2 in arterial blood is known to be invalid. In this study, we
      characterized the associated perfusion errors. Large errors were found when the
      linear assumption is used; these errors were highly dependent on the choice of
      tissue relaxivity. The errors were greatly reduced when using the quadratic
      model, and were further reduced when quantifying perfusion as a relative measure.
      This study suggests the linear assumption should be abandoned in favor of the
      quadratic model. Thus, the errors are minimized leading to improved
      quantification that will enable perfusion MRI to continue to play an important
      role in quantifying perfusion in brain diseases (e.g., acute stroke).

PMID- 19161170
TI  - Broadband slab selection with B1+ mitigation at 7T via parallel spectral-spatial
      excitation.
AB  - Chemical shift imaging benefits from signal-to-noise ratio (SNR) and chemical
      shift dispersion increases at stronger main field such as 7 Tesla, but the
      associated shorter radiofrequency (RF) wavelengths encountered require B1+
      mitigation over both the spatial field of view (FOV) and a specified spectral
      bandwidth. The bandwidth constraint presents a challenge for previously proposed
      spatially tailored B1+ mitigation methods, which are based on a type of
      echovolumnar trajectory referred to as "spokes" or "fast-kz". Although such
      pulses, in conjunction with parallel excitation methodology, can efficiently
      mitigate large B1+ inhomogeneities and achieve relatively short pulse durations
      with slice-selective excitations, they exhibit a narrow-band off-resonance
      response and may not be suitable for applications that require B1+ mitigation
      over a large spectral bandwidth. This work outlines a design method for a general
      parallel spectral-spatial excitation that achieves a target-error minimization
      simultaneously over a bandwidth of frequencies and a specified spatial-domain.
      The technique is demonstrated for slab-selective excitation with in-plane B1+
      mitigation over a 600-Hz bandwidth. The pulse design method is validated in a
      water phantom at 7T using an eight-channel transmit array system. The results
      show significant increases in the pulse's spectral bandwidth, with no additional
      pulse duration penalty and only a minor tradeoff in spatial B1+ mitigation
      compared to the standard spoke-based parallel RF design.

PMID- 19161171
TI  - T2 detection of tumor invasion within segmented components of glioblastoma
      multiforme.
AB  - PURPOSE: To use T2-weighted images to detect tumor invasion when comparing normal
      individuals to groups of gliomablastoma multiforme (GBM) patients with varying
      levels of CXCR4, a chemokine receptor that promotes tumor migration. MATERIALS
      AND METHODS: T2-weighted images were acquired preoperatively in 22 treatment
      naive GBM patients. Two groups were formed based on the expression levels of
      CXCR4. A third group of normal volunteers was used for comparison. Each image was
      segmented to obtain four different clusters for tissue types identified as white
      matter, basal ganglia, gray matter/edema and cerebrospinal fluid (CSF)/tumor.
      Signal intensity histograms were formed for each cluster and compared between
      groups. RESULTS: In every cluster the GBM groups displayed significantly higher
      standard deviations of intensity distributions when compared to normal subjects.
      Significant differences in skewness were found between normal subjects and GBM
      patients in the white matter, basal ganglia, and CSF/tumor. Further, when the two
      groups of GBM patients were compared the CXCR4-high group was found to have a
      significant shift in the median intensity values in the cluster containing gray
      matter and peritumoral edema. CONCLUSION: T2 signal intensity histograms in
      normal subjects differ significantly from those obtained from GBM groups,
      suggesting widespread dissemination of disease.

PMID- 19161172
TI  - Development of the Hospital Nurse Surveillance Capacity Profile.
AB  - Better patient outcomes are often achieved through effective surveillance, a
      primary function of nurses. The purpose of this article is to define,
      operationalize, measure, and evaluate the nurse surveillance capacity of
      hospitals. Nurse surveillance capacity is defined as the organizational features
      that enhance or weaken nurse surveillance. It includes a set of registered nurse
      (staffing, education, expertise, experience) and nurse practice environment
      characteristics. Empirical referents were extracted from existing survey data
      from 9,232 nurses in 174 hospitals. Using a ranking methodology, a Hospital Nurse
      Surveillance Capacity Profile was created for each hospital. Greater nurse
      surveillance capacity was significantly associated with better quality of care
      and fewer adverse events. The profile may assist administrators to improve nurse
      surveillance and patient outcomes.

PMID- 19161174
TI  - Quantitation of brain tissue changes associated with white matter
      hyperintensities by diffusion-weighted and magnetization transfer imaging: the
      LADIS (Leukoaraiosis and Disability in the Elderly) study.
AB  - PURPOSE: To explore the value of diffusion-weighted imaging (DWI) and
      magnetization transfer imaging (MTI) for the improved detection and
      quantification of cerebral tissue changes associated with ageing and white matter
      hyperintensities (WMH). MATERIALS AND METHODS: DWI (n = 340) and MTI (n = 177)
      were performed in nine centers of the multinational Leukoaraiosis And DISability
      (LADIS) study investigating the impact of WMH on 65- to 85-year-old individuals
      without prior disability. We assessed the apparent diffusion coefficient (ADC)
      and magnetization transfer ratio (MTR) of normal appearing brain tissue (NABT)
      and within WMH and related them to subjects' age and WHM severity according to
      the Fazekas score. RESULTS: ADC and MTR values showed a significant inter-site
      variation, which was stronger for the MTR. After z-transformation multiple
      regression analysis revealed WMH severity and age as significant predictors of
      global ADC and MTR changes. Only lesional ADC, but not MTR was related to WMH
      severity. CONCLUSION: ADC and MTR are both sensitive for age and WMH related
      changes in NABT. The ADC is more sensitive for tissue changes within WMH and
      appears to be more robust for multicenter settings.

PMID- 19161175
TI  - In vivo metabolite profile of adult zebrafish brain obtained by high-resolution
      localized magnetic resonance spectroscopy.
AB  - PURPOSE: To optimize high-resolution MR spectroscopy (MRS) for obtaining
      neurochemical composition of adult zebrafish brain in vivo. MATERIALS AND
      METHODS: A flow-through setup for supporting MRS of living zebrafish has been
      designed. In vivo MR microscopy (MRM) images were obtained using a rapid
      acquisition with relaxation enhancement (RARE) sequence to select a volume of
      interest. In vivo MR spectra from zebrafish brain were obtained using an
      optimized point-resolved spectroscopy (PRESS) sequence preceded by a variable
      pulse power and optimized relaxation delays (VAPOR) sequence for global water
      suppression interleaved with outer volume suppression (OVS). In vitro MR spectra
      in the brain extract were obtained by using correlated spectroscopy (COSY)
      sequences. RESULTS: Optimized high-resolution localized MRS at 9.4T in
      conjunction with a strong gradient system, efficient shimming, and the water
      suppression scheme resulted in a reasonable separation of resonances from various
      metabolites in vivo from a voxel as small as 3.3 microL placed in the zebrafish
      brain. In addition, more than 14 metabolites were identified in adult zebrafish
      brain extracts. CONCLUSION: We have successfully optimized a high-resolution
      localized in vivo MRS technique to get access to the zebrafish brain, and
      obtained for the first time the neurochemical composition of the zebrafish brain.

PMID- 19161173
TI  - T(2) relaxometry of normal pediatric brain development.
AB  - PURPOSE: To establish normal age-related changes in the magnetic resonance (MR)
      T(2) relaxation time constants of brain using data collected as part of the
      National Institutes of Health (NIH) MRI Study of Normal Brain Development.
      MATERIALS AND METHODS: This multicenter study of normal brain and behavior
      development provides both longitudinal and cross-sectional data, and has enabled
      us to investigate T(2) evolution in several brain regions in healthy children
      within the age range of birth through 4 years 5 months. Due to the multicenter
      nature of the study and the extended period of data collection, periodically
      scanned inanimate and human phantoms were used to assess intra- and intersite
      variability. RESULTS: The main finding of this work, based on over 340 scans, is
      the identification and parameterization of the monoexponential evolution of T(2)
      from birth through 4 years 5 months of age in various brain structures.
      CONCLUSION: The exponentially decaying T(2) behavior is believed to reflect the
      rapid changes in water content as well as myelination during brain development.
      The data will become publicly available as part of a normative pediatric MRI and
      clinical/behavioral database, thereby providing a basis for comparison in studies
      assessing normal brain development, and studies of deviations due to various
      neurological, neuropsychiatric, and developmental disorders.

PMID- 19161176
TI  - Arterial spin labeling perfusion MRI in pediatric arterial ischemic stroke:
      initial experiences.
AB  - PURPOSE: To investigate the feasibility and utility of arterial spin labeling
      (ASL) perfusion MRI for characterizing alterations of cerebral blood flow (CBF)
      in pediatric patients with arterial ischemic stroke (AIS). MATERIALS AND METHODS:
      Ten children with AIS were studied within 4 to 125 hours following symptom onset,
      using a pulsed ASL (PASL) protocol attached to clinically indicated MR
      examinations. The interhemisphere perfusion deficit (IHPD) was measured in
      predetermined vascular territories and infarct regions of restricted diffusion,
      which were compared with the degree of arterial stenosis and volumes of ischemic
      infarcts. RESULTS: Interpretable CBF maps were obtained in all 10 patients,
      showing simple lesion in nine patients (five hypoperfusion, two hyperperfusion,
      and two normal perfusion) and complex lesions in one patient. Both acute and
      follow-up infarct volumes were significantly larger in cases with hypoperfusion
      than in either hyper- or normal perfusion cases. The IHPD was found to correlate
      with the degree of stenosis, diffusion lesion, and follow-up T(2) infarct
      volumes. Mismatch between perfusion and diffusion lesions was observed. Brain
      regions presenting delayed arterial transit effects were tentatively associated
      with positive outcome. CONCLUSION: This study demonstrates the clinical utility
      of ASL in the neuroimaging diagnosis of pediatric AIS.

PMID- 19161177
TI  - Depression and anxiety in inflammatory bowel disease: a review of comorbidity and
      management.
AB  - While there has been a great deal of speculation over the years on the importance
      of emotional factors in inflammatory bowel disease (IBD), it is only in the last
      decade or so that studies with stronger designs have been available to clarify
      the nature of this relationship. This review considers recent evidence on the
      prevalence of anxiety and depressive disorders in IBD, the role of these
      disorders as a risk factor for IBD onset, the degree to which they affect the
      course of the IBD, and the contribution of corticosteroid treatment to
      psychiatric symptom onset. There is evidence that anxiety and depression are more
      common in patients with IBD and that the symptoms of these conditions are more
      severe during periods of active disease. The few studies that address the issue
      of anxiety and depression as risk factors for IBD do not yet provide enough
      information to support definite conclusions. There is evidence, however, that the
      course of the disease is worse in depressed patients. Treatment with
      corticosteroids can induce mood disorders or other psychiatric symptoms. The
      second part of the review focuses on patient management issues for those with
      comorbid anxiety or depression. Practical approaches to screening are discussed,
      and are recommended for routine use in the IBD clinic, especially during periods
      of active disease. We review evidence-based pharmacological and psychological
      treatments for anxiety and depression and discuss practical considerations in
      treating these conditions in the context of IBD to facilitate overall management
      of the IBD patient.

PMID- 19161178
TI  - Appraisal of the pediatric ulcerative colitis activity index (PUCAI).
AB  - BACKGROUND: We evaluated the psychometric performance of the Pediatric Ulcerative
      Colitis Activity Index (PUCAI) in a real-life cohort from the Pediatric IBD
      Collaborative Research Group. METHODS: Two consecutive visits of 215 children
      with ulcerative colitis (UC) were included (mean age 11.2 +/- 3.6 years; 112
      (52%) males; 63 (29%) newly diagnosed and the others after disease duration of 24
      +/- 15.6 months). Validity was assessed using several constructs of disease
      activity. Distributional and anchor-based strategies were used to assess the
      responsiveness of the PUCAI to change over time following treatment. RESULTS:
      Reflecting feasibility, 97.6% of 770 eligible registry visits had a completed
      PUCAI score versus only 47.6% for a contemporaneously collected Pediatric Crohn's
      Disease Activity Index (odds ratio = 45.8, 95% confidence interval [CI] 28.6
      73.5) obtained for children with Crohn's disease accessioned into the same
      database. The PUCAI score was significantly higher in patients requiring
      escalation of medical therapy (45 points [interquartile range, IQR, 30-60])
      versus those who did not, (0 points [IQR 0-10]; P < 0.001), and was highly
      correlated with physician's global assessment of disease activity (r = 0.9, P <
      0.001). The best cutoff to differentiate remission from active disease was 10
      points (area under receiver operating characteristic curve [AUC] 0.94; 95% CI
      0.90-0.97). Test-retest reliability was excellent (intraclass correlation
      coefficient = 0.89; 95% CI 0.84-0.92, P < 0.001) as well as responsiveness to
      change (AUC 0.96 [0.92-0.99]; standardized response mean 2.66). CONCLUSION: This
      study on real-life, prospectively obtained data confirms that the PUCAI is highly
      feasible by virtue of the noninvasiveness, valid, and responsive index. The PUCAI
      can be used as a primary outcome measure to reflect disease activity in pediatric
      UC.

PMID- 19161179
TI  - Corticosteroids but not infliximab increase short-term postoperative infectious
      complications in patients with ulcerative colitis.
AB  - BACKGROUND: Recent reports suggest that the preoperative use of infliximab (IFX)
      increases postoperative infectious complications in patients with ulcerative
      colitis (UC). Therefore, we determined the impact of IFX on postoperative
      infectious complications. METHODS: A consecutive group of 141 UC patients (41%
      female, median age 39.8 years) undergoing (procto)colectomy was studied.
      Postoperative infectious complications were compared between 22 patients who
      received IFX within 12 weeks prior to (procto)colectomy (IFX group) and 119
      patients who did not (control group). Short-term infectious complications,
      consisting of anastomotic leaks, pelvic abscesses, wound infections, and
      nonsurgical site infections, were recorded within 30 days after primary surgery.
      RESULTS: At primary surgery there was no significant difference in gender,
      disease extent, smoking behavior, body mass index, and concomitant medication
      (including corticosteroids) between the groups. Patients in the IFX group less
      often underwent restorative proctocolectomy without defunctioning ileostomy (9%
      versus 34%, P = 0.022), had a significantly shorter median (interquartile range,
      IQR) disease duration (2.7 [1.2-8.6] versus 5.9 [2.6-13.0] years, P < 0.036) and
      a significantly higher C-reactive protein level at primary surgery (51.7 [9.9
      103.6] versus 19.1 [7.5-42.6] mg/L, P = 0.023). There was no short-term
      mortality. A moderate-to-high dose of corticosteroids (>or=20 mg
      methylprednisolone for >or=2 months, odds ratio 5.19 [95% confidence interval
      [CI]: 1.72-15.66], P = 0.003) and a restorative proctocolectomy without
      defunctioning ileostomy (odds ratio 6.45 [95% CI: 2.12-19.64], P = 0.001) were
      independent predictors of short-term postoperative infectious complications.
      CONCLUSION: Corticosteroids and a restorative proctocolectomy without
      defunctioning ileostomy, but not IFX, are associated with an increased risk of
      short-term postoperative infectious complications in UC.

PMID- 19161180
TI  - Upregulation of T-bet and tight junction molecules by Bifidobactrium longum
      improves colonic inflammation of ulcerative colitis.

PMID- 19161181
TI  - MR study of the effect of infarct size and location on left ventricular
      functional and microstructural alterations in porcine models.
AB  - PURPOSE: To investigate the effect of infarct size and location on left
      ventricular (LV) functional and microstructural alterations in well-established
      porcine models. MATERIALS AND METHODS: Myocardium infarction was induced in mini
      pigs at apical septum (Group 1, n = 6) or basal lateral wall (Group 2, n = 6) by
      permanent occlusion of the left anterior descending or left circumflex coronary
      artery, respectively. In vivo cardiac magnetic resonance (CMR) was performed 4
      and 13 weeks later. Hearts were then excised and examined by ex vivo diffusion
      tensor imaging (DTI) for myocardium structural changes in infarct, adjacent and
      remote regions. RESULTS: LV ejection fractions correlated negatively with infarct
      sizes. Between week 4 and 13, Group 1 exhibited more changes in end-systolic
      volume, LV mass, and ejection fraction, although it showed a smaller infarct
      volume percentage. Ex vivo results revealed the decreased water diffusion
      fractional anisotropy and increased diffusivities in infarct region in
      correlation with infarct size, but with no significant difference between the two
      groups. However, LV myocardial double-helical fiber architecture was found to
      alter in Group 1, shifting more towards left-handed direction as compared to
      controls. CONCLUSION: Postinfarct LV functional and structural remodeling is
      affected by both infarct size and location.

PMID- 19161182
TI  - Feasibility of dobutamine stress cardiovascular magnetic resonance imaging in
      children.
AB  - PURPOSE: To evaluate the feasibility of dobutamine stress magnetic resonance
      (DSMR) in pediatric patients. MATERIALS AND METHODS: The medical records of all
      DSMR studies performed on patients < or =22 years old at a single institution
      were retrospectively reviewed. The DSMR protocol included dobutamine doses up to
      40 microg/kg/minute and atropine to attain the target heart rate [0.85 . (220 -
      age)]. RESULTS: Thirty-two DSMR studies were performed in 28 patients (median age
      = 7.3 years; range = 0.8-22 years). Twenty of the studies were performed under
      general anesthesia. The protocol was completed in 26 studies, technical problems
      and interruptions were few, and image quality scores (1-5) for all ventricular
      wall segments were high (mean = 4.2). A heart rate > or =160 bpm was attained in
      84% of the studies, a rate pressure product > or =20,000 beats . mm Hg in 87%,
      and a heart rate greater than or equal to the target heart rate in 19%. No
      serious adverse events occurred. One patient had an inducible wall motion
      abnormality. Interobserver agreement was 100% (kappa = 1.0) for test positivity
      and 92% (kappa = 0.72) for wall motion scores. CONCLUSION: DSMR in pediatric
      patients is feasible and provides high-quality imaging of all ventricular wall
      segments with low interobserver variability. Further exploration of DSMR in
      pediatric patients is warranted, particularly for those children who are unable
      to cooperate sufficiently for exercise stress or have poor acoustic windows.

PMID- 19161183
TI  - Coronary anomalies assessed by whole-heart isotropic 3D magnetic resonance
      imaging for cardiac morphology in congenital heart disease.
AB  - PURPOSE: To determine the value of whole-heart three-dimensional magnetic
      resonance imaging (MRI) for coronary artery imaging in children/adolescents with
      congenital heart disease (CHD). MATERIALS AND METHODS: Forty children/adolescents
      (median age: 14 years, range 2.6-25.8) with CHD underwent free-breathing
      navigator-gated isotropic three-dimensional steady-state free-precession (3D
      SSFP) MRI for cardiac morphology. Two observers independently evaluated
      visibility of origin, course, vessel lengths, image quality (IQ), and contrast
      between coronary lumen and myocardium. A subgroup was compared with cardiac
      catheter. RESULTS: The total scan time was 6.3 +/- 3.2 minutes (mean +/- SD, at
      mean heart rate 76 +/- 15/min). The mean vessel length for right coronary artery
      (RCA) by observer 1 was 97 +/- 43 mm (observer 2: 94 +/- 37 mm), for left main
      and anterior descending artery (LM/LAD) 91 +/- 40 mm (observer 2: 90 +/- 40 mm),
      and for left circumflex artery (LCX) 64 +/- 28mm (observer 2: 66 +/- 28 mm). The
      mean vessel contrast was 0.34 +/- 0.05 (range: 0.23-0.45; maximum = 1, minimum =
      0). On a 4-level score (1 = nondiagnostic, 4 = excellent), mean IQ scores ranged
      between 2.3-2.9 (+/-0.8-1.0). Both observers agreed on the presence/proximal
      course of RCA in 40/40, LM/LAD in 38/40, and LCX in 36/40 patients. There was
      complete agreement with invasive coronary angiography available in 12/40 patients
      (six anomalies). CONCLUSION: Isotropic whole-heart 3D-MRI for cardiac morphology
      allows reliable discrimination between normal and abnormal coronary anatomy in
      children/adolescents with CHD.

PMID- 19161184
TI  - Differentiation of well-differentiated hepatocellular carcinomas from other
      hepatocellular nodules in cirrhotic liver: value of SPIO-enhanced MR imaging at
      3.0 Tesla.
AB  - PURPOSE: To determine the diagnostic value of superparamagnetic iron oxide (SPIO)
      enhanced MRI for the differentiation of well-differentiated hepatocellular
      carcinomas (WD-HCCs) from other hepatocellular nodules in cirrhotic liver.
      MATERIALS AND METHODS: This study included 114 patients with 216 histologically
      confirmed hepatocellular nodules, i.e., 23 dysplastic nodules (DNs), 37 WD-HCCs,
      and 156 moderately or poorly differentiated HCCs (MD-/PD HCCs), who underwent
      SPIO-enhanced MRI at 3.0T. MRI included T2-weighted fast-spin echo and T2*
      weighted gradient recalled echo (GRE) sequences before and after administration
      of ferucarbotran. The contrast-to-noise ratio (CNR) of the lesion was calculated.
      Reviewers analyzed signal intensity (SI) of the nodules and their enhancement
      features on SPIO-enhanced images. Sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy in the diagnosis of WD-HCC were
      also calculated. RESULTS: The mean CNR of WD-HCC was significantly higher than
      that of DN on T2*-weighted image. Incomplete high SI on SPIO-enhanced T2*
      weighted images were seen in 56.8% of WD-HCC. The most prevalent enhancement
      features of WD-HCCs on SPIO-enhanced T2*-weighted images, were iso SI with high
      SI foci [32.5% (12/37)] and homogenous subtle high SI [24.3% (9/37)].
      Alternatively, 22 of 23 DNs (95.7%) showed low- or iso SI, and 145 of 156 (94.9%)
      MD-/PD HCCs showed strong high SI. When iso SI with high SI foci or subtle
      homogenous high SI nodule was considered as diagnostic criteria for WD-HCC, we
      could identify 56.8% of the WD-HCCs but only 4.4% of the DNs and 3.2% of the MD
      /PD HCCs. CONCLUSION: WD-HCCs have characteristic enhancement features that
      differentiate them from DNs and MD-/PD HCCs on SPIO-enhanced 3.0T MRI. The lesion
      conspicuity was better on T2*-weighted images than that on T2-weighted
      images.Inc.

PMID- 19161185
TI  - Comparison of diffusion-weighted MRI and 2-[fluorine-18]-fluoro-2-deoxy-D-glucose
      positron emission tomography (FDG-PET) for detecting primary colorectal cancer
      and regional lymph node metastases.
AB  - PURPOSE: To examine the usefulness of diffusion-weighted MRI (DW-MRI) for the
      detection of both primary colorectal cancer and regional lymph node metastases,
      and compare its performance with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose
      positron emission tomography (FDG-PET) in the same patients. MATERIALS AND
      METHODS: We studied 25 patients with known colorectal cancer. All underwent both
      DW-MRI and FDG-PET studies. The images were retrospectively assessed by visual
      inspection and the imaging findings were compared with histopathological findings
      on surgical specimens. RESULTS: Of the 27 primary colorectal lesions surgically
      excised in 25 patients, 23 (85.2%) were true-positive on both DW-MRI and FDG-PET.
      Two cancers were false-negative on DW-MRI but true-positive on FDG-PET, and two
      were false-negative on both DW-MRI and FDG-PET. With respect to the detectability
      of metastatic lymph nodes, DW-MRI and FDG-PET manifested a sensitivity of 80%
      (8/10) and 30.0% (3/10), a specificity of 76.9% (10/13) and 100% (13/13), and an
      accuracy of 78.3% (18/23) and 69.6% (16/23), respectively. CONCLUSION: DW-MRI is
      inferior to FDG-PET for the detection of primary lesions, but superior for the
      detection of lymph node metastases.

PMID- 19161186
TI  - Added value of breathhold diffusion-weighted MRI in detection of small
      hepatocellular carcinoma lesions compared with dynamic contrast-enhanced MRI
      alone using receiver operating characteristic curve analysis.
AB  - PURPOSE: To evaluate the added value of single-breathhold diffusion-weighted MRI
      (DWI) in detection of small hepatocellular carcinoma (HCC) lesions (< or =2 cm)
      in patients with chronic liver disease, by comparing the detection sensitivity of
      combined DWI/conventional dynamic contrast-enhanced (DCE)-MRI to that of
      conventional DCE-MRI alone. MATERIALS AND METHODS: A total of 37 patients with
      chronic liver diseases underwent abdominal MRI at 1.5T, including T1-weighted
      imaging (T1WI), T2-weighted imaging (T2WI), and 2D conventional DCE. For each
      patient study, axial DWI was performed with a single-shot echo-planar imaging
      (EPI) sequence using a modified sensitivity-encoding (mSENSE) technique with b
      value of 500 seconds/mm(2). A total of 20-24 slices were obtained during a 15-17
      second breathhold. Two observers independently interpreted the combined
      DWI/conventional DCE-MRI images and the conventional DCE-MRI images alone in
      random order. For all small HCC lesions, the diagnostic performance using each
      imaging set was evaluated by receiver operating characteristic (ROC) curve
      analysis. Sensitivity and positive predictive values were also calculated and
      analyzed. RESULTS: A total of 47 small HCCs were confirmed as final result. The
      area under the ROC curve (Az) of combined DWI/conventional DCE-MRI images
      (observer 1, 0.922; observer 2, 0.918) were statistically higher than those of
      conventional DCE-MRI alone (observer 1, 0.809; observer 2, 0.778) for all small
      HCC lesions (P < 0.01). The lesion detection sensitivities using the combined
      technique for both observers were significantly higher than those using
      conventional DCE-MRI alone (P < 0.01). The sensitivity values for two observers
      using the combined technique were 97.87% and those using conventional DCE-MRI
      alone were 85.11% to 82.98%. The positive predictive values for two observers
      using the combined imaging technique (97.87%) were slightly higher than those
      using conventional DCE-MRI alone (92.86-93.02%), but there was no significant
      difference between the two imaging sets. CONCLUSION: Combined use of breathhold
      DWI with conventional DCE-MRI helped to provide higher sensitivities than
      conventional DCE-MRI alone in the detection of small HCC lesions in patients with
      chronic liver disease.

PMID- 19161187
TI  - Pancreatic diffusion-weighted imaging (DWI): comparison between mass-forming
      focal pancreatitis (FP), pancreatic cancer (PC), and normal pancreas.
AB  - PURPOSE: To compare diffusion-weighted imaging (DWI) findings and the apparent
      diffusion coefficient (ADC) values of pancreatic cancer (PC), mass-forming focal
      pancreatitis (FP), and the normal pancreas. MATERIALS AND METHODS: DWI (b = 0 and
      600 seconds/mm(2)) findings of 14 patients with mass-forming FP proven by
      histopathology and or clinical follow-up, 10 patients with histopathologically
      proven PC, and 14 subjects with normal pancreatic exocrine function and normal
      imaging findings were retrospectively evaluated. ADC values of the masses, the
      remaining pancreas, and the normal pancreas were measured. RESULTS: On b = 600
      seconds/mm(2) DWI, mass-forming FP was visually indistinguishable from the
      remaining pancreas whereas PC was hyperintense relative to the remaining
      pancreas. The mean ADC value of PC (1.46 +/- 0.18 mm(2)/second) was significantly
      lower than the remaining pancreas (2.11 +/- 0.32 x 10(-3) mm(2)/second; P <
      0.0001), mass-forming FP (2.09 +/- 0.18 x 10(-3) mm(2)/second; P < 0.0001), and
      pancreatic gland in the control group (1.78 +/- 0.07 x 10(-3) mm(2)/second; P <
      0.0005). There was no significant difference of ADC values between the mass
      forming focal pancreatitis and the remaining pancreas (2.03 +/- 0.2 x 10(-3)
      mm(2)/second; P > 0.05). CONCLUSION: Differences on DWI may help to differentiate
      PC, mass-forming FP, and normal pancreas from each other.

PMID- 19161189
TI  - Diagnosis of complete cul-de-sac obliteration (CCDSO) by the MRI jelly method.
AB  - PURPOSE: To evaluate the usefulness of MRI jelly method (jelly method). MATERIALS
      AND METHODS: Fifty-five patients (32.7 +/- 5 years old) with endometriosis,
      treated with laparoscopic surgery between January and June 2005 with preoperative
      MRI using the jelly method. In imaging by the jelly method, 50 mL of jelly used
      for ultrasound was injected into the vagina, and 150 mL of jelly diluted twice
      with tap water was injected into the rectum. MRI were inspected for the following
      seven findings: (Finding 1) Uterine position (anteflexion or retroflexion);
      (Finding 2) Thickness of the posterior uterine wall (adenomyosis uteri); (Finding
      3) Ascites in the Douglas' pouch; (Finding 4) Elevated posterior uterine fornix;
      (Finding 5) Thickening of the "Haustra"; (Finding 6) Elevated anterior rectal
      wall; and (Finding 7) Douglas' pouch lesion visualized as a high-intensity area
      on a T1-weighted image. The latter four findings were enhanced with the jelly
      method. These seven findings were examined for their correlations with video
      findings of adhesion during surgery. RESULTS: CCDSO was present in 30 of 55
      patients. These seven findings had accuracies of 69.1%, 70.9%, 72.7%, 74.5%,
      56.4%, 83.6%, and 81.8% respectively. Findings 6 and 7 showed high accuracy.
      CONCLUSION: These two findings could only be obtained using the jelly method,
      indicating the usefulness of this method for diagnosing CCDSO.

PMID- 19161188
TI  - Spleen R2 and R2* in iron-overloaded patients with sickle cell disease and
      thalassemia major.
AB  - PURPOSE: To evaluate the magnetic properties of the spleen in chronically
      transfused, iron-overloaded patients with sickle cell disease (SCD) and
      thalassemia major (TM) and to compare splenic iron burdens to those in the liver,
      heart, pancreas, and kidneys. MATERIALS AND METHODS: A retrospective analysis of
      63 TM and 46 SCD patients was performed. Spleen R2 and R2* values were calculated
      from spin-echo and gradient-echo images collected between April 2004 and
      September 2007. RESULTS: The spleen showed a different R2-R2* relationship than
      that previously established for the liver. At high iron concentrations (R2* > 300
      Hz), spleen R2 was lower than predicted for liver. The proportion of splenic to
      hepatic iron content was greater in SCD patients compared with TM patients (23.8%
      vs. 13.8%). A weak association was found between splenic and liver iron-this
      association was stronger in SCD patients. Little correlation was found between
      splenic iron and extrahepatic R2* values. CONCLUSION: For spleen and liver tissue
      with the same R2* value, splenic R2 was significantly lower than hepatic R2,
      particularly for R2* > approximately 300 Hz. Splenic iron levels have little
      predictive value for R2* values of heart, pancreas, and kidney.

PMID- 19161190
TI  - Estimates of glomerular filtration rate from MR renography and tracer kinetic
      models.
AB  - PURPOSE: To compare six methods for calculating the single-kidney glomerular
      filtration rate (GFR) from T(1)-weighted magnetic resonance (MR) renography (MRR)
      against reference radionuclide measurements. MATERIALS AND METHODS: In 10
      patients, GFR was determined using six published methods: the Baumann-Rudin model
      (BR), the Patlak-Rutland method (PR), the two-compartment model without bolus
      dispersion (2C) and with dispersion (2CD), the three-compartment model (3CD), and
      the distributed parameter model (3C-IRF). Reference single-kidney GFRs were
      measured by radionuclide renography. The coefficient of variation of GFR (CV) was
      determined for each method by Monte Carlo analyses for one healthy and one
      dysfunctional kidney at a noise level (sigma(n)) of 2%, 5%, and 10%. RESULTS: GFR
      estimates in patients varied from 6% overestimation (BR) to 50% underestimation
      (PR and 2CD applied to cortical data). Correlations with reference GFRs ranged
      from R = 0.74 (2CD, cortical data) to R = 0.85 (BR). In simulations, the lowest
      CV was produced by 3C-IRF in healthy kidney (1.7sigma(n)) and by PR in diseased
      kidney ((2.2-2.4)sigma(n)). In both kidneys the highest CV was obtained with 2CD
      ((5.9-8.2)sigma(n)) and with 3CD in diseased kidney (8.9sigma(n) at sigma(n) =
      10%). CONCLUSION: GFR estimates depend on the renal model and type of data used.
      Two- and three-compartment models produce comparable GFR correlations.

PMID- 19161191
TI  - Relative apparent diffusion coefficient: determination of reference site and
      validation of benefit for detecting metastatic lymph nodes in uterine cervical
      cancer.
AB  - PURPOSE: To determine the reference site for relative apparent diffusion
      coefficient (rADC) and to evaluate the benefit of rADC for detecting metastatic
      lymph nodes in uterine cervical cancer. MATERIALS AND METHODS: Two observers
      independently measured ADCs in the spleen, liver, renal cortex, lumbar spine,
      lumbar spinal cord, and gluteus maximus on diffusion-weighted images (b value, 0
      and 1000 mm/sec(2)) in 50 patients. The reference site for rADC was determined
      using the intra- and interobserver coefficient of variation (CV) of ADC in these
      organs. rADC was calculated by ADC(lesion)/ADC(reference site). The benefit of
      rADC over ADC was validated by comparing the area under the receiver operating
      curve for identifying metastatic lymph nodes in uterine cervical cancer in 130
      patients. RESULTS: The renal cortex was determined to be the reference site for
      rADC, as its CVs (intraobserver, 5%-7%; interobserver, 5%) were less than those
      of the other organs (P < 0.05). The ADC and rADC of metastatic lymph nodes (n =
      29, ADC, 0.7483 x 10(-3) mm(2)/sec; rADC, 0.3832) were less than those of
      nonmetastatic lymph nodes (n = 229, ADC, 0.9960 x 10(-3) mm(2)/sec; rADC, 0.5383)
      (P < 0.05). The area under the receiver operating characteristics curve for
      differentiating metastatic from nonmetastatic lymph nodes was greater for rADC
      (0.914; 95% confidence interval [CI], 0.872-0.945) than for ADC (0.872; 95% CI,
      0.825-0.910) (P = 0.007). CONCLUSION: The renal cortex is an appropriate
      reference site for rADC and rADC may improve the accuracy for diagnosing
      metastatic lymph nodes in uterine cervical cancer.

PMID- 19161192
TI  - Metabolic alterations: a biomarker for radiation-induced normal brain injury-an
      MR spectroscopy study.
AB  - PURPOSE: To assess if interval changes in metabolic status in normal cerebral
      tissue after radiation therapy (RT) can be detected by 2D CSI (chemical shift
      imaging) proton spectroscopy. MATERIALS AND METHODS: Eleven patients with primary
      brain tumors undergoing cranial radiation therapy (RT) were included. 2D-CSI MRS
      was performed before, during, and after the course of RT with the following
      parameters: TE/TR 144/1500 ms, field of view (FOV) 24, thickness 10 mm, matrix 16
      x 16. The metabolic ratios choline/creatine (Cho/Cr), N-acetylaspartate (NAA)/Cr,
      and NAA/Cho in normal brain tissue were calculated. RESULTS: NAA/Cr and Cho/Cr
      were significantly decreased at week 3 during RT and at 1 month and 6 months
      after RT compared to values prior to RT (P < 0.01). The NAA/Cr ratio decreased by
      -0.19 +/- 0.05 (mean +/- standard error [SE]) at week 3 of RT, -0.14 +/- 0.06 at
      the last week of RT, -0.14 +/- 0.05 at 1 month after RT, and -0.30 +/- 0.08 at 6
      months after RT compared to the pre-RT value of 1.43 +/- 0.04. The Cho/Cr ratio
      decreased by -0.27 +/- 0.05 at week 3 of RT, -0.11 +/- 0.05 at the last week of
      RT, -0.26 +/- 0.05 at 1 month after RT and -0.25 +/- 0.07 at 6 months after RT
      from the pre-RT value of 1.29 +/- 0.03. Changes in Cho/Cr were correlated with
      the interaction of the radiation dose and dose-volume at week 3 of RT, during the
      last week of RT (P < 0.005), and at 1 month after RT (P = 0.017). CONCLUSION: The
      results of this study suggest that MRS can detect early metabolic changes in
      normal irradiated brain tissue.

PMID- 19161193
TI  - Quantification of regional functional improvement of infarcted myocardium after
      primary PTCA by contrast-enhanced magnetic resonance imaging.
AB  - PURPOSE: To assess with cardiac magnetic resonance imaging (CMR) the relationship
      between treatment delay and improvement of regional left ventricular function
      after primary percutaneous transluminal coronary angioplasty (p-PTCA) for acute
      myocardial infarction (AMI). MATERIALS AND METHODS: We performed cine- and late
      enhancement (LE) CMR in 40 patients with first AMI after restoring TIMI 3 flow
      with p-PTCA and at a follow-up 4 months later. Infarcted segments were determined
      from LE images. Regional left ventricular function was quantified from cine-CMR
      images. Segmentation followed the American Heart Association 17-segments model.
      Patients were divided into groups with delay <3 hours, 3-6 hours, 6-12 hours, and
      a delay >12 hours. RESULTS: Segmental wall thickening (SWT) significantly iproved
      only in segments reperfused within 6 hours (P < 0.001). Follow-up SWT was
      significantly higher if segments were reperfused early (<3 hours: 74 +/- 4%, 3-6
      hours: 57 +/- 4%, 6-12 hours: 48 +/- 7%, <3 to 3-6: P < 0.003, and <3 to 6-12
      hours: P < 0.001). The extent of improvement was greater if delay was <3 hours
      compared to segments with a delay of >3 hours (<3 hours: +21 +/- 3%, 3-6 hours:
      +8 +/- 4%, 6-12 hours: +6 +/- 3%; <3 hours to 3-6 hours, and 6-12 h, P < 0.02).
      CONCLUSION: We quantitatively demonstrated that time to p-PTCA treatment
      significantly influences regional functional recovery of infarcted myocardium at
      a 4-month follow-up.

PMID- 19161194
TI  - Prediction of locally recurrent prostate cancer after radiation therapy:
      incremental value of 3T diffusion-weighted MRI.
AB  - PURPOSE: To prospectively evaluate the incremental value of diffusion-weighted
      imaging (DWI) with apparent diffusion coefficient (ADC) maps in addition to T2
      weighted imaging (T2WI) for predicting locally recurrent prostate cancer in
      patients with biochemical failure after radiation therapy. MATERIALS AND METHODS:
      Thirty-six consecutive patients with an increased prostate-specific antigen level
      after radiation therapy underwent 3T MRI followed by transrectal biopsy. The MRI
      findings and biopsy results were correlated in sextant prostate sectors of
      peripheral zones (PZs). Two radiologists in consensus reviewed T2WI and combined
      T2WI and DWI with ADC maps, and rated the likelihood of recurrent cancer on a
      five-point scale. ADC values were calculated for recurrent cancer and benign
      tissue. RESULTS: Of 216 sectors, 65 prostate sectors (30%) were positive for
      cancer in 18 patients. For predicting recurrent cancer, combined T2WI and DWI
      showed a greater sensitivity compared to T2WI (P < 0.001). A significantly
      greater area under the receiver operating characteristics curve (Az) was
      determined for combined T2WI and DWI (Az = 0.879, P < 0.01) as compared to T2WI
      (Az = 0.612). Mean ADC values between recurrent cancer and benign tissue showed a
      statistically significant difference (P < 0.01). CONCLUSION: For predicting
      locally recurrent prostate cancer after radiation therapy, the use of combined
      T2WI and DWI showed a better diagnostic performance compared to T2WI.

PMID- 19161195
TI  - Age dependence of T1 perfusion MRI-based hemodynamic parameters in human kidneys.
AB  - PURPOSE: To determine the association between renal cortical perfusion parameters
      from T1-DCE magnetic resonance imaging (MRI) and age in human kidney. MATERIALS
      AND METHODS: Thirty-five patients (mean age: 53 years, SD = 15 years) were imaged
      using inversion recovery (IR)-prepared FLASH (pulse repetition time [TR] = 4.4
      msec, echo time [TE] 2.2 msec, inversion time [TI] = 180 msec, FA 50 degrees ,
      matrix 128 x 256, 0.3 sec/slice) during the injection of Gadolinium-DTPA. Tissue
      concentration-time courses were deconvolved. Renal blood flow (RBF), volume of
      distribution (RVD), and mean transit time (MTT) were derived from the resulting
      impulse response function. RESULTS: Mean RBF, RVD, and MTT were 127 mL/min/100 mL
      (SD = 81 mL/min/100 mL), 40 mL/100 mL (SD 23 mL/100 mL), and 22 sec (SD = 9 sec).
      A significant moderately negative correlation was found between RBF and age (R = 
      0.447, P = 0.007), RVD and age (R = -0.420, P = 0.012). MTT and age did not show
      a significant correlation (R = 0.017, P = 0.924). Repeating this analysis for
      each gender revealed a moderate age dependence of RBF (R = -0.600 with P = 0.009)
      and RVD (R = -0.540 with P = 0.021) in the male group only. CONCLUSION: T1-DCE
      quantitative perfusion MRI was sufficiently sensitive to demonstrate a
      significant negative correlation of RBF and RVD with patient age. This was due to
      a moderate age dependence of these quantities in males that seems to be absent in
      females.

PMID- 19161197
TI  - Ultrashort TE spectroscopic imaging (UTESI): application to the imaging of short
      T2 relaxation tissues in the musculoskeletal system.
AB  - PURPOSE: To investigate ultrashort TE spectroscopic imaging (UTESI) of short T2
      tissues in the musculoskeletal (MSK) system. MATERIALS AND METHODS: Ultrashort TE
      pulse sequence is able to detect rapidly decaying signals from tissues with a
      short T2 relaxation time. Here a time efficient spectroscopic imaging technique
      based on a multiecho interleaved variable TE UTE acquisition is proposed for high
      resolution spectroscopic imaging of the short T2 tissues in the MSK system. The
      projections were interleaved into multiple groups with the data for each group
      being collected with progressively increasing TEs. The small number of
      projections in each group sparsely but uniformly sampled k-space. Spectroscopic
      images were generated through Fourier transformation of the time domain images at
      variable TEs. T2* was quantified through exponential fitting of the time domain
      images or line shape fitting of the magnitude spectrum. The feasibility of this
      technique was demonstrated in volunteer and cadaveric specimen studies on a
      clinical 3T scanner. RESULTS: UTESI was applied to six cadaveric specimens and
      four human volunteers. High spatial resolution and contrast images were generated
      for the deep radial and calcified layers of articular cartilage, menisci,
      ligaments, tendons, and entheses, respectively. Line shape fitting of the UTESI
      magnitude spectroscopic images show a short T2* of 1.34 +/- 0.56 msec, 4.19 +/-
      0.68 msec, 3.26 +/- 0.34 msec, 1.96 +/- 0.47 msec, and 4.21 +/- 0.38 msec,
      respectively. CONCLUSION: UTESI is a time-efficient method to image and
      characterize the short T2 tissues in the MSK system with high spatial resolution
      and high contrast.

PMID- 19161196
TI  - MRI-based thermal dosimetry and diffusion-weighted imaging of MRI-guided focused
      ultrasound thermal ablation of uterine fibroids.
AB  - PURPOSE: To investigate tissue changes observed in diffusion-weighted imaging
      (DWI) and its relation to contrast imaging, thermal dosimetry, and changes in the
      apparent diffusion coefficient (ADC) after MRI-guided focused ultrasound surgery
      (MRgFUS) of uterine fibroids. MATERIALS AND METHODS: Imaging data were analyzed
      from 45 fibroids in 42 women treated with MRgFUS. The areas of the hyperintense
      regions in DWI and of nonperfused regions in T1-weighted contrast enhanced
      imaging (both acquired immediately after treatment) were compared with each other
      and to thermal dosimetry based estimates. Changes in ADC were also calculated.
      RESULTS: Hyperintense regions were observed in 35/45 fibroids in DWI. When
      present, the areas of these regions were comparable on average to the thermal
      dose estimates and to the nonperfused regions, except for in several large
      treatments in which the nonperfused region extended beyond the treated area. ADC
      increased in 19 fibroids and decreased in the others. CONCLUSION: DWI changes,
      which includes changes in both in T2 and ADC, may be useful in many cases to
      delineate the treated region resulting from MRgFUS. However, clear DWI changes
      were not always observed, and in some large treatments, the extent of the
      nonperfused region was under estimated. ADC changes immediately after MRgFUS were
      unpredictable.

PMID- 19161198
TI  - Evaluation of measurement uncertainties in human diffusion tensor imaging (DTI)
      derived parameters and optimization of clinical DTI protocols with a wild
      bootstrap analysis.
AB  - PURPOSE: To quantify measurement uncertainties of fractional anisotropy, mean
      diffusivity, and principal eigenvector orientations in human diffusion tensor
      imaging (DTI) data acquired with common clinical protocols using a wild bootstrap
      analysis, and to establish optimal scan protocols for clinical DTI acquisitions.
      MATERIALS AND METHODS: A group of 13 healthy volunteers were scanned using three
      commonly used DTI protocols with similar total scan times. Two important
      parameters-the number of unique diffusion gradient directions (NUDG) and the
      ratio of the total number of diffusion-weighted (DW) images to the total number
      of non-DW images (DTIR)-were analyzed in order to investigate their combined
      effects on uncertainties of DTI-derived parameters, using results from both the
      Monte Carlo simulation and the wild bootstrap analysis of uncertainties in human
      DTI data. RESULTS: The wild bootstrap analysis showed that uncertainties in human
      DTI data are significantly affected by both NUDG and DTIR in many brain regions.
      These results agree with previous predictions based on error-propagations as well
      as results from simulations. CONCLUSION: Our results demonstrate that within a
      clinically feasible DTI scan time of about 10 minutes, a protocol with number of
      diffusion gradient directions close to 30 provides nearly optimal measurement
      results when combined with a ratio of the total number of DW images over non-DW
      images equal to six. Wild bootstrap can serve as a useful tool to quantify the
      measurement uncertainty from human DTI data.

PMID- 19161199
TI  - Improved fat suppression using multipeak reconstruction for IDEAL chemical shift
      fat-water separation: application with fast spin echo imaging.
AB  - PURPOSE: To evaluate and quantify improvements in the quality of fat suppression
      for fast spin-echo imaging of the knee using multipeak fat spectral modeling and
      IDEAL fat-water separation. MATERIALS AND METHODS: T(1)-weighted and T(2)
      weighted fast spin-echo sequences with IDEAL fat-water separation and two
      frequency-selective fat-saturation methods (fat-selective saturation and fat
      selective partial inversion) were performed on 10 knees of five asymptomatic
      volunteers. The IDEAL images were reconstructed using a conventional single-peak
      method and precalibrated and self-calibrated multipeak methods that more
      accurately model the NMR spectrum of fat. The signal-to-noise ratio (SNR) was
      measured in various tissues for all sequences. Student t-tests were used to
      compare SNR values. RESULTS: Precalibrated and self-calibrated multipeak IDEAL
      had significantly greater suppression of signal (P < 0.05) within subcutaneous
      fat and bone marrow than fat-selective saturation, fat-selective partial
      inversion, and single-peak IDEAL for both T(1)-weighted and T(2)-weighted fast
      spin-echo sequences. For T(1)-weighted fast spin-echo sequences, the improvement
      in the suppression of signal within subcutaneous fat and bone marrow for
      multipeak IDEAL ranged between 65% when compared to fat-selective partial
      inversion to 86% when compared to fat-selectivesaturation. For T2-weighted fast
      spin-echo sequences, the improvement for multipeak IDEAL ranged between 21% when
      compared to fat-selective partial inversion to 81% when compared to fat-selective
      saturation. CONCLUSION: Multipeak IDEAL fat-water separation provides improved
      fat suppression for T(1)-weighted and T(2)-weighted fast spin-echo imaging of the
      knee when compared to single-peak IDEAL and two widely used frequency-selected
      fat-saturation methods.

PMID- 19161200
TI  - Assessment of anterior cruciate ligament reconstruction using 3D ultrashort echo
      time MR imaging.
AB  - This work demonstrates the potential of ultrashort TE (UTE) imaging for
      visualizing graft material and fixation elements after surgical repair of soft
      tissue trauma such as ligament or meniscal injury. Three asymptomatic patients
      with anterior cruciate ligament (ACL) reconstruction using different graft
      fixation methods were imaged at 1.5T using a 3D UTE sequence. Conventional
      multislice turbo spin-echo (TSE) measurements were performed for comparison. 3D
      UTE imaging yields high signal from tendon graft material at isotropic spatial
      resolution, thus facilitating direct positive contrast graft visualization.
      Furthermore, metal and biopolymer graft fixation elements are clearly depicted
      due to the high contrast between the signal-void implants and the graft material.
      Thus, the ability of UTE MRI to visualize short-T(2) tissues such as tendons,
      ligaments, or tendon grafts can provide additional information about the status
      of the graft and its fixation in the situation after cruciate ligament repair.
      UTE MRI can therefore potentially support diagnosis when problems occur or
      persist after surgical procedures involving short-T(2) tissues and implants.

PMID- 19161201
TI  - Evaluation of the translational and rotational forces acting on a highly
      ferromagnetic orthopedic spinal implant in magnetic resonance imaging.
AB  - PURPOSE: To assess the translational and rotational forces acting on a highly
      ferromagnetic orthopedic spinal implant in 1.5T and 3.0T magnetic resonance (MR)
      systems. MATERIALS AND METHODS: The translational forces and rotational forces,
      or torques, acting on the implant were measured using existing methods and
      assessed using the guidelines produced by the American Society for Testing and
      Materials (ASTM). RESULTS: The measured translational forces were many times
      greater than for any other orthopedic implant previously recorded in the
      literature and, based on deflection angle criteria, would be considered unsafe in
      both MR systems. However, due to the rigid fixation of orthopedic implants in
      bone, implant migration is considered highly unlikely. Several constituent
      components of the implant were subjected to large torques, in some cases an order
      of magnitude greater than the corresponding torque due to gravity. However, the
      counterbalancing effect of the configuration of the combined implant results in a
      net torque that is less than the torque due to gravity. CONCLUSION: The
      translational and rotational forces acting on the implant in both 1.5T and 3.0T
      MR systems are substantial, but based on theoretical considerations are unlikely
      to result in implant migration or rotation.

PMID- 19161202
TI  - Contiguous-slice zonally oblique multislice (CO-ZOOM) diffusion tensor imaging:
      examples of in vivo spinal cord and optic nerve applications.
AB  - PURPOSE: To describe and demonstrate a new technique that allows diffusion tensor
      imaging of small structures such as the spinal cord (SC) and optic nerve (ON)
      with contiguous slices and reduced image distortions using a narrow field of view
      (FOV). MATERIALS AND METHODS: Images were acquired with a modified single-shot
      echo-planar imaging (EPI) sequence that contains a refocusing radio frequency
      (RF) pulse in the presence of the phase-encoding (rather than slice-select)
      gradient. As a result, only a narrow volume may be both excited and refocused,
      removing the problem of signal aliasing for narrow FOVs. Two variants of this
      technique were developed: cardiac gating is included in the study of the SC to
      reduce pulsation artifacts, whereas inversion-recovery (IR) cerebrospinal fluid
      (CSF) suppression is utilized in the study of the ON to eliminate partial volume
      effects. The technique was evaluated with phantoms, and mean diffusivity (MD) and
      fractional anisotropy (FA) measurements were made in the SC and ON of two healthy
      volunteers. RESULTS: The technique provides contiguous-slice, reduced-FOV images
      that do not suffer from aliasing and have reduced magnetic susceptibility
      artifacts. MD and FA values determined here lie within the ranges quoted in the
      literature. CONCLUSION: Contiguous-slice zonally orthogonal multislice (CO-ZOOM
      EPI is a new technique for diffusion-weighted imaging of small structures such as
      the ON and SC with high resolution and reduced distortions due to susceptibility
      variations. This technique is able to acquire contiguous slices that may allow
      further nerve-tracking analyses.

PMID- 19161203
TI  - 7T head volume coils: improvements for rostral brain imaging.
AB  - PURPOSE: To improve the performance of 7T head coils over the rostral head
      regions. Due to radiofrequency (RF) field/tissue interactions, the RF magnetic
      field profile produced by 7T volume head coils is very inhomogeneous, with
      enhanced sensitivity near the center of the human brain and substantially reduced
      in the periphery. MATERIALS AND METHODS: Two head-sized quadrature volume coils
      of similar diameters but substantially different lengths (17 and 10 cm) were
      constructed and tested using a 7T Varian Inova system. RESULTS: Experimental data
      demonstrated that by using a shorter volume head-sized coil or simply by
      partially moving a head out of the coil, coil efficiency near the top of a head
      can be improved by 20%. The homogeneity also improved, largely resulting from an
      increase in peripheral B(1) values. This resulted in 10%-20% variation in axial
      slices located near the top of a head. CONCLUSION: We have demonstrated a less
      deeply positioned head or substantially shorter volume coil can significantly
      improve coil performance and homogeneity for the rostral head at ultrahigh
      magnetic fields (7T and above). For studies that target superior brain regions,
      this coil arrangement can be highly effective.

PMID- 19161204
TI  - Acquisition and reconstruction of undersampled radial data for myocardial
      perfusion magnetic resonance imaging.
AB  - PURPOSE: To improve myocardial perfusion magnetic resonance imaging (MRI) by
      reconstructing undersampled radial data with a spatiotemporal constrained
      reconstruction method (STCR). MATERIALS AND METHODS: The STCR method jointly
      reconstructs all of the time-frames for each slice. In 7 subjects at rest, on a 3
      T scanner, the method was compared with a conventional (GRAPPA) Cartesian
      approach. RESULTS: Increased slice coverage was obtained, as compared with
      Cartesian acquisitions. On average, 10 slices were obtained per heartbeat for
      radial acquisitions (8 of which are suitable for visual analysis with the
      remaining 2 slices, in theory, usable for quantitative purposes), whereas 4
      slices were obtained for the conventional Cartesian acquisitions. The new method
      was robust to interframe motion, unlike using Cartesian undersampling and STCR.
      STCR produced images with an image quality rating (1 for best and 5 for worst) of
      1.7 +/- 0.5; the Cartesian images were rated 2.6 +/- 0.4 (P = 0.0006). A mean
      improvement of 44 (+/-17) in signal-to-noise (SNR) ratio and 46 (+22) in contrast
      to-noise ratio (CNR) was observed for STCR. CONCLUSION: The new radial data
      acquisition and reconstruction scheme for dynamic myocardial perfusion imaging is
      a promising approach for obtaining significantly higher coverage and improved SNR
      ratios. Further testing of this approach is warranted during vasodilation in
      patients with coronary artery disease.

PMID- 19161205
TI  - Non-contrast-enhanced MR angiography for selective visualization of the hepatic
      vein and inferior vena cava with true steady-state free-precession sequence and
      time-spatial labeling inversion pulses: preliminary results.
AB  - PURPOSE: To selectively visualize the hepatic vein and inferior vena cava (IVC)
      using three-dimensional (3D) true steady-state free-precession (SSFP) MR
      angiography with time-spatial labeling inversion pulse (T-SLIP), and to optimize
      the acquisition protocol. MATERIALS AND METHODS: Respiratory-gated 3D true SSFP
      scans were conducted in 23 subjects in combination with two different T-SLIPs
      (one placed in the thorax to suppress the arterial signal and the other in the
      abdomen to suppress the portal venous signal). One of the most important factors
      was the inversion time (TI) of abdominal T-SLIP, and the image quality was
      evaluated at four different TIs of 800, 1200, 1600, and 2000 msec in terms of
      relative signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and mean
      visualization scores. RESULTS: No significant difference was observed in SNR and
      CNR between each TI. However, IVC visualization scores were better at TIs of 1600
      and 2000 msec, and overall image quality was better at TIs of 1200 and 1600 msec.
      Therefore, the TI of 1600 msec was considered to provide the optimal balance
      between IVC visualization and signal suppression of the portal vein in our
      protocol. CONCLUSION: True SSFP scan with T-SLIPs enabled selective visualization
      of the hepatic vein and IVC without an exogenous contrast agent.

PMID- 19161206
TI  - Interleaved T(1) and T(2) relaxation time mapping for cardiac applications.
AB  - PURPOSE: To diagnose acute myocardial infarction (MI) with MRI, T(1)-weighted and
      T(2)-weighted images are required to detect necrosis and edema. The calculation
      of both T(1) and T(2) maps can be relevant for quantitative diagnosis. In this
      work, we present a simultaneous quantification of T(1)-T(2) relaxation times of a
      short-axis view of the heart in a single scan. MATERIALS AND METHODS: An
      electrocardiograph (ECG)-triggered, navigator-gated, interleaved T(1) and T(2)
      mapping sequence was implemented for the quantification of the T(1) and T(2)
      values of phantoms, healthy volunteers, and three patients with acute MI. The
      proposed acquisition scheme consisted of an interleaved two-dimensional (2D)
      steady-state free precession (SSFP) sequence with three different modules: an
      inversion-recovery (IR) sequence with multiple time delays, followed by a delay
      of one cardiac cycle for magnetization recovery and a T(2)-preparation pulse with
      multiple echo-times for T(2) quantification. RESULTS: Measurements of in vivo
      relaxation times were in good agreement with literature values. The interleaved
      sequence was able to measure T(1) and T(2) relaxation times of the myocardium.
      CONCLUSION: The interleaved sequence acquires data for the calculation of T(1)
      and T(2) maps in only one scan without the need for registration. This technique
      has the potential to differentiate between acute and chronic MI by estimating the
      concentration of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) in the
      necrotic tissue and to assess the extent of edema from T(2) maps.

PMID- 19161207
TI  - A qualitative exploration of emotional inhibition: a basic emotions and
      developmental perspective.
AB  - In recent years, emotional inhibition (EI) has come to be regarded as an
      important transdiagnostic concept within cognitive-behavioural
      theories/therapies. However, there is still a paucity of empirical knowledge on
      understanding EI's development, maintenance and consequences within
      psychopathology. It was due to this lack of research that this study used an
      exploratory/qualitative approach to investigate EI. This study used a grounded
      theory methodology to gather and analyse analogue data from 10 university
      students who had scored significantly high on a measure of EI. The results of
      this study highlighted four main overarching themes regarding the development and
      maintenance of EI: (1) emotional development in childhood; (2) current strategies
      for coping with emotions which included EI strategies; (3) beliefs about
      emotions; and (4) the impact of EI. Key points included modelling and lack of
      emotional support in childhood, negative beliefs about emotions and the perceived
      consequences of experiencing or expressing them, the influence that other people
      have on emotional expression and the paradoxical nature of EI. Once the data had
      been collected and analysed, links were then made between the findings of this
      research and the current literature base. A general model of EI development and
      maintenance is proposed in the discussion.

PMID- 19161208
TI  - The Personality Structure Questionnaire (PSQ): a cross-validation with a large
      clinical sample.
AB  - In a large sample of adult National Health Service (NHS) patients (initially n =
      1296) referred for psychological therapy, the Personality Structure Questionnaire
      (PSQ) items were found to constitute a unidimensional scale according to maximum
      likelihood and principal component analyses, and by Cronbach's alpha criteria.
      The PSQ scores showed a significant small negative association with age, where
      higher scores indicate pathology; but no sex difference was found. Scores remain
      stable during time spent on the waiting list, but were reduced significantly
      following therapy of an equivalent length of time (median = 15 weeks). The
      intercorrelations between the three clusters of items (sub-concepts, as proposed
      by the test authors) comprising the full PSQ varied, but were all sizeable and
      highly statistically significant. Additional information to that of the test
      authors is provided on convergent and discriminant validity through its
      correlations with psychological tests and clinicians' ratings. Suggestions are
      made for the possible further improvement and refinement of the questionnaire.

PMID- 19161209
TI  - Mapping of T1-values and Gadolinium-concentrations in MRI as indicator of disease
      activity in luminal Crohn's disease: a feasibility study.
AB  - PURPOSE: To determine the feasibility of T1-mapping and calculation of Gadolinium
      values in luminal Crohn's Disease (CD). MATERIALS AND METHODS: Nine patients with
      active CD were included. For each patient disease activity was determined, based
      on endoscopic and histopathological results. The Crohn's Disease Endoscopic Index
      of Severity (CDEIS), the Harvey-Bradshaw index (HBI) and C-reactive protein (CRP)
      were also determined as reference standards. T1-measurements were performed
      before and after intravenous administration of Gadodiamide in 14 slices in a
      single breath-hold using the Look-Locker (LL) sequence in combination with a
      segmented three-dimensional Turbo Field Echo sequence. A Region of Interest (ROI)
      was drawn around inflamed bowel loops and the mean Gadolinium-concentration
      within the ROI was calculated. Gadolinium-concentrations were compared between
      patients with mild and marked disease, as determined by the reference standards.
      RESULTS: Mean Gadolinium-concentrations were higher in bowel loops of patients
      with more active disease, as defined by endoscopic and histopathological
      examination, CRP, and HBI. CONCLUSION: By using a breath-hold LL sequence in the
      bowel quantitative assessment of contrast agent concentration is possible, thus
      permitting objective evaluation of physiological changes in actively inflamed
      tissue in an area that suffers from motion problems.

PMID- 19161210
TI  - Value of precontrast T(1) for dGEMRIC of native articular cartilage.
AB  - PURPOSE: To evaluate if the difference between pre- and post-Gd-DTPA(2-)
      relaxation rate (DeltaR(1)) provides better differentiation of osteoarthritic
      patients (OA) from healthy subjects (HS) with dGEMRIC, as compared to post-Gd
      DTPA(2-) spin-lattice relaxation time (T(1Gd)). MATERIALS AND METHODS: Seventeen
      OA and 14 HS underwent pre- and 90 minutes postcontrast (Gd-DTPA(2-)) magnetic
      resonance imaging (MRI) of the knee, using inversion recovery fast spin-echo
      and/or Lock-Locker sequences for T(1) mapping. Effect sizes for T(1pre), T(1Gd),
      and DeltaR(1) were calculated, and receiver operating characteristic (ROC) curve
      and regression analysis were also performed to assess the effectiveness of each
      parameter in the separation of OA and HS. RESULTS: T(1Gd) and DeltaR(1) were
      almost identical in terms of areas under ROC curves (0.903 and 0.914,
      respectively), and effect sizes (1.34 and 1.31, respectively). These were
      significantly higher than T(1pre). In addition, a high inverse correlation was
      observed between DeltaR(1) vs. T(1Gd) (R = 0.96). CONCLUSION: Either T(1Gd) or
      DeltaR(1) could be used as an index in the evaluation of native cartilage.
      However, considering the practical logistical cost involved in terms of time and
      effort to acquire precontrast T(1) measurements, our data further support the
      continued use of T(1Gd) as the dGEMRIC index in the evaluation of native
      cartilage.

PMID- 19161211
TI  - Transit-time method to demonstrate whether or not an impedance matching occurs at
      the pulmonary junction.

PMID- 19161214
TI  - Water-soluble calix[4]resorcinarenes as chiral NMR solvating agents for bicyclic
      aromatic compounds.
AB  - Water-soluble calix[4]resorcinarenes with proline, 3-hydroxyproline, and 4
      hydroxyproline substituent groups are evaluated as chiral NMR solvating agents on
      a series of bicyclic aromatic compounds with naphthyl, indole, dihydroindole, and
      indane rings. The substrates interact with the calixresorcinarene through
      insertion of the aromatic ring into the cavity. Most of the substrates are
      analyzed as cationic species, although one anionic species is analyzed. All of
      the substrates exhibit enantiomeric discrimination in the 1H-NMR spectrum with
      one or more of the calixresorcinarenes. In most cases, the hydroxyproline
      derivatives are more effective at causing enantiodifferentiation than the
      corresponding proline derivative. Presumably, the hydroxyl group on the proline
      moieties is involved in interactions with the substituent groups of the substrate
      that are important in creating chiral recognition. The enantiomeric
      discrimination in the 1H-NMR spectrum is large enough for many resonances to
      permit the analysis of enantiomeric purity.

PMID- 19161215
TI  - Influence of quinidine, cimetidine, and ketoconazole on the enantioselective
      pharmacokinetics and metabolism of metoprolol in rats.
AB  - Metoprolol is a beta-blocker and its racemic mixture is used for the treatment of
      hypertension. In the present study we investigated the influence of CYP2D and
      CYP3A on the stereoselective metabolism of metoprolol in rats. Male Wistar rats
      (n = 6 per group) received racemic metoprolol (15 mg/kg) orally, with or without
      pretreatment with the CYP inhibitor ketoconazole (50 mg/kg), cimetidine (150
      mg/kg), or quinidine (80 mg/kg). Blood samples were collected up to 48 h after
      metoprolol administration. The plasma concentrations of the stereoisomers of
      metoprolol, O-demethylmetoprolol (ODM), alpha-hydroxymetoprolol (OHM) (Chiralpak
      AD column), and metoprolol acidic metabolite (AODM) (Chiralcel OD-R column) were
      determined by HPLC using fluorescence detection (lambda(exc) = 229 nm; lambda(em)
      = 298 nm). CYP3A inhibition by ketoconazole reduced the plasma concentrations of
      ODM and AODM and favored the formation of OHM. CYP2D and CYP3A inhibition by
      cimetidine reduced the plasma concentrations of OHM and AODM and favored the
      formation of ODM. The inhibition of CYP2D by quinidine reduced the plasma
      concentrations of OHM and favored the formation of ODM. In conclusion, the
      results suggest that CYP3A is involved in the formation of ODM and CYP2D is
      involved in the formation of AODM.

PMID- 19161216
TI  - Desymmetrization of cyclic anhydrides mediated by cinchona alkaloids: synthesis
      and olfactory properties of new fragrances based on (R)- and (S)-2-ethylhexanol.
AB  - A series of enantiomerically pure new fragrances, derived from 2-ethylhexanol,
      have been prepared and their olfactory properties evaluated. The key step of the
      synthesis is cinchona-alkaloid-catalyzed desymmetrization of cyclic meso
      anhydrides with (R)- and (S)-2-ethylhexanol and proceeded in good to excellent
      diastereoselectivities (92:8-98:2 dr). Enantiomerically pure alcohols were
      prepared by lipase-catalyzed kinetic resolution of 2-ethylhexanol using vinyl
      laurate as acyl donor.

PMID- 19161219
TI  - NMR enantiodifferentiation of quaternary ammonium salts of Troger base.
AB  - Hexacoordinated phosphorus BINPHAT anion 1 is an efficient NMR chiral solvating
      agent for quaternary ammonium cations (quats) derived from Troger base leading to
      large separations of the proton signals of the enantiomers and even in polar
      solvent media such as CD(3)CN (Delta Delta delta up to 0.12 ppm). Quite
      surprisingly, this efficacy in the NMR split efficiency is not translated into a
      supramolecular stereocontrol (Pfeiffer effect) of the cation configuration by the
      anion.

PMID- 19161217
TI  - Determination of the absolute configuration of aromatase and dual aromatase
      sulfatase inhibitors by vibrational and electronic circular dichroism spectra
      analysis.
AB  - The absolute configuration of a newly designed, letrozole-based chiral aromatase
      inhibitor that could not be defined by crystallographic techniques has been
      determined by means of vibrational and electronic circular dichroism and by
      optical rotation measurements combined with density functional theory
      calculations on possible conformers. The same absolute configurational assignment
      can be applied to the individual enantiomeric sulfamate esters, which are derived
      from the corresponding enantiomers of the chirally separated parent phenols,
      based on the similarity of the ECD spectrum of the sulfamate derivative to that
      of its phenolic precursor. The two enantiomeric sulfamate esters studied here are
      the first examples of nonsteroidal dual aromatase-sulfatase inhibitor whose
      activities have been evaluated on optically resolved enantiomers.

PMID- 19161220
TI  - Separation and toxicity of salithion enantiomers.
AB  - Enantioseletive toxicities of chiral pesticides have become an environmental
      concern recently. In this study, we evaluated the enantiomeric separation of
      salithion on a suite of commercial chiral columns and assessed the toxicity of
      enantiomers toward butyrylcholinesterase and Daphnia magna. Satisfactory
      separations of salithion enantiomers could be achieved on all tested columns,
      that is, Chiralcel OD, Chiralcel OJ, and Chiralpak AD column. However, the
      Chiralpak AD column offered the best separation and was chosen to prepare micro
      scale of pure salithion enantiomers for subsequent bioassays. The first and
      second enantiomers eluted on the Chiralpak AD column were further confirmed to be
      (-)-S-salithion and (+)-R-salithion, respectively. The half inhibition
      concentrations to butyrylcholinesterase of racemate, (+)-R-salithion, and (-)-S
      salithion were 33.09, 2.92, and 15.60 mg/l, respectively, showing (+)-R
      enantiomer being about 5.0 times more potent than its (-)-S-form. However, the
      median lethal concentrations (96 h) of racemate, (+)-R-salithion, and (-)-S
      salithion toward D. magna were 3.54, 1.10, and 0.36 microg/l, respectively,
      suggesting that (-)-S-salithion was about 3.0 times more toxic than (+)-R-form.
      Racemic salithion was less toxic than either of the enantiomers in both
      bioassays, suggesting that antagonistic interactions might occur between the
      enantiomers during the toxication action. This work reveals that the toxicity of
      salithion toward butyrylcholinesterase and D. magna is enantioselective, and this
      factor should be taken into consideration in the environmental risk assessment of
      salithion.

PMID- 19161221
TI  - Tamoxifen-dependent, inducible Hoxb6CreERT recombinase function in lateral plate
      and limb mesoderm, CNS isthmic organizer, posterior trunk neural crest, hindgut,
      and tailbud.
AB  - The ability to generate conditional mutant alleles in mice using Cre-lox
      technology has facilitated analysis of genes playing critical roles in multiple
      developmental processes at different times. We used a transgenic Hoxb6 promoter
      to drive tamoxifen-dependent Cre recombinase expression in several developing
      systems that serve as major models for elucidating inductive interactions and
      mechanisms of morphogenesis, including lateral plate mesoderm and descendant limb
      buds, neural crest progenitors of the neural tube, tailbud, and CNS isthmic
      organizer. The Hoxb6CreER(T) line gives very rapid and complete recombination
      over a short time window after a single tamoxifen dose, allowing precise time
      requirements for gene function to be assessed accurately. Embryonic cells
      cultured from the Hoxb6CreER(T) line also display rapid recombination ex vivo
      after tamoxifen exposure. Hence, the Hoxb6CreER(T) line provides a valuable tool
      for analyzing gene function, as well as lineage tracing studies using genetic
      cell marking, in several developing systems.

PMID- 19161223
TI  - Formaldehyde-based whole-mount in situ hybridization method for planarians.
AB  - Whole-mount in situ hybridization (WISH) is a powerful tool for visualizing gene
      expression patterns in specific cell and tissue types. Each model organism
      presents its own unique set of challenges for achieving robust and reproducible
      staining with cellular resolution. Here, we describe a formaldehyde-based WISH
      method for the freshwater planarian Schmidtea mediterranea developed by
      systematically comparing and optimizing techniques for fixation,
      permeabilization, hybridization, and postprocessing. The new method gives robust,
      high-resolution labeling in fine anatomical detail, allows co-labeling with
      fluorescent probes, and is sufficiently sensitive to resolve the expression
      pattern of a microRNA in planarians. Our WISH methodology not only provides
      significant advancements over current protocols that make it a valuable asset for
      the planarian community, but should also find wide applicability in WISH methods
      used in other systems.

PMID- 19161222
TI  - Coronary endothelial proliferation and morphogenesis are regulated by a VEGF
      mediated pathway.
AB  - Though development of the coronary vasculature is a critical event during
      embryogenesis, the molecular mechanisms that regulate its formation are not well
      characterized. Two unique approaches were used to investigate interactions
      between cardiac myocytes and proepicardial (PE) cells, which are the coronary
      anlagen. One of these experimental approaches used a 3-D collagen scaffold system
      on which specific cell-cell and cell-matrix interactions were studied. The other
      approach used a whole heart culture system that allowed for the analysis of
      epicardial to mesenchymal transformation (EMT). The VEGF signaling system has
      been implicated previously as an important regulator of coronary development. Our
      results demonstrated that a specific isoform of VEGF-A, VEGF(164), increased PE
      derived endothelial cell proliferation and also increased EMT. However, VEGF
      stimulated endothelial cells did not robustly coalesce into endothelial tubes as
      they did when cocultured with cardiac myocytes. Interestingly, blocking VEGF
      signaling via flk-1 inhibition reduced endothelial tube formation despite the
      presence of cardiac myocytes. These results indicate that VEGF signaling is
      complex during coronary development and that combinatorial signaling by other
      VEGF-A isoforms or other flk-1-binding VEGFs are likely to regulate endothelial
      tube formation.

PMID- 19161224
TI  - FGF receptor dependent regulation of Lhx9 expression in the developing nervous
      system.
AB  - LIM-homeodomain (LIM-hd) proteins form a multifunctional family of transcription
      factors that plays critical roles in the development of progenitor and post
      mitotic cells. Considerable work has focused on what regulates their expression
      post-mitotically in the spinal cord. However, little is known about what
      regulates LIM-hd genes at earlier developmental stages. To address this question,
      we explored the role of fibroblast growth factor (FGF) signalling in regulating
      the expression of a Xenopus laevis Lhx9 orthologue (XLhx9). XLhx9 is first
      expressed in the eye field and hindbrain, and when FGF receptor (FGFR) activation
      was inhibited prior to its onset, both brain and eye field expression was
      diminished. However, when FGFRs were inhibited after XLhx9 onset, retinal
      expression remained strong and brain expression was again diminished. These data
      suggest that while FGF signalling initiates and maintains brain XLhx9 expression,
      in the eye primordium the requirement of FGFs for expression is rapidly lost.

PMID- 19161225
TI  - Differential expression of sphingosine-1-phosphate receptors 1-5 in the
      developing nervous system.
AB  - Sphingosine-1-phosphate (S1P) binds to G protein-coupled receptors and can
      regulate a wide range of cellular functions. In a previous study, we isolated two
      key enzymes in the S1P pathway that were expressed in migrating neural crest
      cells. To determine if S1P receptors are present in neural crest cells or
      peripheral nervous system, we examine the expression patterns of S1P receptors
      (S1pr1-5) in mouse, and s1pr1 and s1pr3 in chick embryos. Here, we present a
      comprehensive expression analysis of these receptors using in situ
      hybridizations, which provide spatiotemporal information. We showed that S1pr2
      was expressed in migrating cranial neural crest cells and enteric neurons. S1pr1
      was prominently expressed in the neuroepithelium whereas S1pr4 and S1pr5 were in
      neurons at later stages. On the contrary, S1pr3 was predominantly detected in non
      neuronal cells within and surrounding neural structures. We also described novel
      expression sites for S1P receptors in the developing nervous system.

PMID- 19161226
TI  - gfap and nestin reporter lines reveal characteristics of neural progenitors in
      the adult zebrafish brain.
AB  - Adult neurogenesis arises from niches that harbor neural stem cells (NSC).
      Although holding great promise for regenerative medicine, the identity of NSC
      remains elusive. In mammals, a key attribute of NSC is the expression of the
      filamentous proteins glial fibrillary acidic protein (GFAP) and NESTIN. To assess
      whether these two markers are relevant in the fish model, two transgenic
      zebrafish lines for gfap and nestin were generated. Analysis of adult brains
      showed that the fusion GFAP-green fluorescent protein closely mimics endogenous
      GFAP, while the nestin transgene recapitulates nestin at the ventricular zones.
      Cells expressing the two reporters display radial glial morphology, colocalize
      with the NSC marker Sox2, undergo proliferation, and are capable of self-renewal
      within the matrix of distinct thickness in the telencephalon. Together, these two
      transgenic lines reveal a conserved feature of putative NSC in the adult
      zebrafish brain and provide a means for the identification and manipulation of
      these cells in vivo.

PMID- 19161231
TI  - Microcystin extracts induce ultrastructural damage and biochemical disturbance in
      male rabbit testis.
AB  - In the present research, the changes of ultrastructures and biochemical index in
      rabbit testis were examined after i.p. injection with 12.5 microg/kg microcystin
      (MC) extracts. Ultrastructural observation showed widened intercellular junction,
      distention of mitochondria, endoplasmic reticulum, and Golgi apparatus. All these
      changes appeared at 1, 3, and 12 h, but recovered finally. In biochemical
      analyses, the levels of lipid peroxidation (MDA) and H(2)O(2) increased
      significantly at 1 h, indicating MC-caused oxidative stress. Finally, H(2)O(2)
      decreased to the normal levels, while MDA remained at high levels. The
      antioxidative enzymes (CAT, SOD, GPx, GST) and antioxidants (GSH) also increased
      rapidly at 1 h, demonstrating a quick response of the defense systems to the
      oxidative stress. Finally, the activity of CAT, SOD, and GPX recovered to the
      normal level, while the activity of GST and the concentration of GSH remained at
      a high level. This suggests that the importance of MCs detoxification by GST via
      GSH, and the testis of rabbit contained abundant GSH. The final recovery of
      ultrastructure and some biochemical indexes indicates that the defense systems
      finally succeeded in protecting the testis against oxidative damage. In
      conclusion, these results indicate that the MCs are toxic to the male rabbit
      reproductive system and the mechanism underlying this toxicity might to be the
      oxidative stress caused by MCs. Although the negative effects of MCs can be
      overcome by the antioxidant system of testis in this study, the potential
      reproductive risks of MCs should not be neglected because of their wide
      occurrence.

PMID- 19161227
TI  - Ligand-specific function of transforming growth factor beta in epithelial
      mesenchymal transition in heart development.
AB  - The ligand specificity of transforming growth factor beta (TGFbeta) in vivo in
      mouse cardiac cushion epithelial-to-mesenchymal transition (EMT) is poorly
      understood. To elucidate the function of TGFbeta in cushion EMT, we analyzed
      Tgfb1(-/-), Tgfb2(-/-), and Tgfb3(-/-) mice between embryonic day (E) 9.5 and
      E14.5 using both in vitro and in vivo approaches. Atrioventricular (AV) canal
      collagen gel assays at E9.5 indicated normal EMT in both Tgfb1(-/-) and Tgfb3(-/
      ) mice. However, analysis of Tgfb2(-/-) AV explants at E9.5 and E10.5 indicated
      that EMT, but not cushion cell proliferation, was initially delayed but later
      remained persistent. This was concordant with the observation that Tgfb2(-/-)
      embryos, and not Tgfb1(-/-) or Tgfb3(-/-) embryos, develop enlarged cushions at
      E14.5 with elevated levels of well-validated indicators of EMT. Collectively,
      these data indicate that TGFbeta2, and not TGFbeta1 or TGFbeta3, mediates cardiac
      cushion EMT by promoting both the initiation and cessation of EMT.

PMID- 19161232
TI  - Cadmium-induced infertility in male mice.
AB  - The effects of cadmium in a concentration similar to that found in Maharloo Lake
      (Shiraz, Iran) on male reproductive system was studied in adult Balb/c male mice
      that received 0, 23, and 50 mg/kg of cadmium chloride in 0.5 mL distilled water
      for 45 days. Sperm count and motility, sperm nuclear maturity and chromatin
      structure tests were carried out. Testis of each mouse was examined
      histologically. The treated male mice were mated with females. Prostatic and
      nonprostatic acid phosphatase activity in blood serum, testis, and prostate,
      lipid peroxidation and cadmium accumulation in testis, seminal vesicle, and
      middle 1/3 of the quadericeps femoris muscle were measured. The sperm count,
      sperm motility, sperm maturity, and the level of testosterone decreased
      significantly in the high dose adminstered group. Histological studies showed a
      severe necrosis and atrophy in the testis of high dose group, consequently, there
      was no successful mating in some groups. The number of newborns and their weights
      and crown rump lengths reduced. Cadmium accumulation in testis and middle of the
      quadriceps femoris muscle was significantly higher in animals receiving 50 mg/kg
      cadmium chloride. Nonprostatic acid phosphatase activity decreased, whereas
      prostatic acid phosphatase activity increased significantly in serum of animals
      receiving 50 mg/kg cadmium chloride. Also prostatic acid phosphatase activity
      decreased significantly in prostate of animals receiving 50 mg/kg cadmium
      chloride. Lipid peroxidation was significantly higher in testis of animals
      treated with 50 mg/kg cadmium chloride compared with control group. Cadmium
      affects male reproductive system activity and can cause infertility in mice as an
      animal model.

PMID- 19161233
TI  - Seasonal succession of Cylindrospermopsis raciborskii and Aphanizomenon
      ovalisporum blooms with cylindrospermopsin occurrence in the volcanic Lake
      Albano, Central Italy.
AB  - The cyanobacterial toxin cylindrospermopsin is rapidly spreading in the European
      temperate Countries. Cylindrospermopsin was detected for the first time in Italy
      in 2004; in this study, the presence of this toxin in Albano Lake (Central Italy)
      has been correlated to the cyanobacterial species Cylindrospermopsis raciborskii
      and Aphanizomenon ovalisporum and their population dynamics. In 2004, these two
      species succeeded in the lake during spring, summer, and early autumn without
      overlapping, causing superficial blooms. Cylindrospermopsin was detected in lake
      samples by LC-MS/MS and ELISA immunoassay, showing extracellular superficial
      values ranging from 2.6 to 126 microg/L, and water column values ranging from
      0.41 to 18.4 microg/L. Twenty-six of 30 positive water samples (86%) exceeded the
      recommended limit of 1 microg/L. Intracellular values up to 42.3 microg/g were
      measured. Moreover, cylindrospermopsin was detected in tissues from two Salmo
      trutta trouts (up to 2.7 ng/g) and in a well for drinking water supply (1.6
      microg/L). For the first time, two cyanobacterial species producing
      cylindrospermopsin were detected in the same lake in Italy.

PMID- 19161234
TI  - Assessment of the toxicological interaction of sertraline with cholinesterase
      inhibiting insecticides in aquatic insects using the black fly, Simulium vittatum
      IS-7.
AB  - Sertraline is a selective serotonin reuptake inhibitor (SSRI) prescribed as an
      antidepressant. Although SSRIs are known to block serotonin reuptake sites on
      cell membranes, they also have been shown to inhibit acetylcholinesterase (AChE)
      activity. Thus, the interaction of these chemicals with other AChE inhibitors,
      namely, organophosphate and carbamate insecticides, is of interest. In addition,
      these insecticides have been shown to interact with serotonergic neuronal
      pathways creating questions as to how these chemicals might interact. In this
      study, the interactive effect of sertraline (SSRI) in binary combinations with
      carbaryl (carbamate insecticide) and diazinon (organophosphate insecticide) was
      assessed using a 48-h acute toxicity test with black fly larvae, Simulium
      vittatum IS-7. Results showed that observed mortality was bracketed by the
      independent action model and concentration addition model with the independent
      action model slightly underestimating mortality and the concentration addition
      model slightly overestimating mortality. Varying the concentration of the
      chemicals in the mixture did not indicate that sertraline was interacting with
      the insecticides to make them more toxic or vice versa. These results indicate
      that sertraline and the insecticides are likely eliciting toxicity at separate
      neuronal pathways since no interaction was observed.

PMID- 19161235
TI  - Testing of different plants to determine influence of physico-chemical properties
      and contaminants content on municipal sewage sludges phytotoxicity.
AB  - This study attempts to evaluate the Phytotoxkit as a tool for measuring the
      toxicity of municipal sewage sludges using 10 common plants: mustard, turnip,
      cress, red clover, cucumber, tomato, radish, sorrel, and spinach. The results
      were used to determine a germination index (GI) and a median effective
      concentration (EC) value for each plant. The trace metal and polycyclic aromatic
      hydrocarbon (PAH) contaminant content and the physical-chemical properties were
      examined. Most sewage sludges were characterized by an unfavorable electrical
      conductivity value of about 5.2 mS/cm(-1). The most abundant trace metals were
      zinc (Zn) at 871-1680 mg kg(-1), manganese (Mn) at 245-661 mg kg(-1), and copper
      (Cu) at 88.2-161.0 mg kg(-1). The lowest values were determined for cobalt (Co)
      at 2.9-3.8 mg kg(-1) and cadmium (Cd) at 0.7-3.7 mg kg(-1). The PAH sum was based
      on 10 individual compounds (USE EPA), and the PAH content ranged from 4.76 to
      27.95 mg kg(-1), most of the sewage sludges showing a predomination by
      carcinogenic PAHs. The GI values, based on seed germination and root growth
      inhibition bioassays, showed increasing plant sensitivity to the tested sewage
      sludges in the following order: cress > turnip > mustard > sorrel > tomato >
      sorgo > red clover > radish > cucumber > spinach. The EC50 sewage sludge values
      lay in the range 31-404 g/kg of soil, and significant relationships were found
      for most of the plants between EC50 and the magnesium content (Mg(2+): alpha =
      0.888-0.924, P = 0.05), calcium content (Ca(2+): alpha = 0.813-0.911, P < or =
      0.05), and pH (alpha = -0.913-0.948, P = 0.05). In the case of sewage sludge
      pollutants, significant relationships were found for trace metals such as:
      strontium (Sr: alpha = 0.851-0.948, P < or = 0.05), chromium (Cr: alpha = 0.858,
      P < or = 0.05), and nickel (Ni: alpha = 0.955, P = 0.05), as well as pyrene
      (PAHs).

PMID- 19161236
TI  - Validation of a new yeast-based reporter assay consisting of human estrogen
      receptors alpha/beta and coactivator SRC-1: application for detection of
      estrogenic activity in environmental samples.
AB  - Endocrine disruptors are exogenous substances that act like hormones in the
      endocrine system and disrupt the physiologic function of endogenous hormones. In
      the present study, we established reporter yeast strains (Saccharomyces
      cerevisiae) expressing human estrogen receptors, ERalpha or ERbeta. These strains
      contain a reporter plasmid carrying an estrogen responsive element (ERE) upstream
      of the beta-galactosidase gene, and a plasmid expressing a steroid receptor
      coactivator, SRC-1e. Using these reporter strains, we demonstrated dose-dependent
      estrogenic activities of different categories of ligands, a natural hormone,
      17beta-estradiol (E2); a synthetic drug, diethylstilbestrol (DES);
      phytoestrogens, genistein, daizein and emodin; and an environmental endocrine
      disrupter, bisphenol A. EC(50) values of E2 for ERalpha and ERbeta are 5.31 x 10(
      10) and 5.85 x 10(-10) M, respectively. We also demonstrated that these yeasts
      were applicable for measuring estrogenic activities of environmental water
      samples. Most downstream sites of a river showed similar activity in both ERalpha
      and ERbeta assays. These yeast strains are useful and convenient for detecting
      and comparing the estrogenic ligand activities of environmental samples in
      response to ERalpha and ERbeta.

PMID- 19161237
TI  - Endoplasmic reticulum may not be involved in the lead-induced apoptosis in PC 12
      cells in vitro.
AB  - Recent researches indicated that mitochondrial pathway might play an important
      role in lead-induced apoptosis. Our previous study also found that lead could
      induce apoptosis in PC 12 cells, and mitochondrial pathway events were involved
      in this process. As lead can disturb Ca(2+) homeostasis, the present study was
      undertaken to determine whether lead can activate key cellular events in the
      endoplasmic reticulum (ER) pathway, including the expressions of C/EBP homology
      protein (CHOP) and glucose-regulated protein 78 (GRP78), and the activation of
      caspase-12 and calpain. The results showed that lead could increase the
      expression of GRP78, while the expressions of CHOP and procaspase-12 remained
      unchanged. Moreover, the caspase-12 and calpain were not activated, and the
      ultrastructure of endoplasmic reticulum was not altered. Therefore, it suggests
      that lead may induce apoptosis in PC 12 cells through mitochondrial pathway, but
      not through the endoplasmic reticulum pathway.

PMID- 19161238
TI  - Blood lead levels in children of Lucknow, India.
AB  - After implementing measures to control lead pollution in many countries, blood
      lead levels (BLLs) in children have been declined. The phase-out of leaded petrol
      began in Lucknow, the capital of most populated state, Uttar Pradesh in India on
      April 1, 2000. We evaluated the mean BLL and associated risk factors for lead
      exposure in Lucknow children (3-12 years) after petrol lead phase-out activity.
      The mean BLL of the 200 children was 9.3 microg/dL (range: 1.0-27.9 microg/dL).
      Seventy-four children (37%) had BLL above the Centre for Disease Control and
      Prevention's (CDC) level of concern (10 microg/dL). When these data were compared
      with BLLs determined by the George Foundation among the children of Mumbai,
      Bangalore, Kolkata, Chennai, Hyderabad, and Delhi during the year 1997 when
      leaded petrol was in use, where 62%, 62%, 87%, 96%, 43%, and 95%, respectively,
      then exceeded the CDC intervention level. Further, BLL of present study was very
      close to Mumbai children (age < or =12 years) estimated following the
      introduction of unleaded petrol, and 33% children had BLL above the CDC concern
      level with an average 8.4 microg/dL. Low socioeconomic status, proximity of home
      to traffic density, and mother's illiteracy were the factors associated with
      elevated BLLs in Lucknow children (P < 0.05). Overall, results indicate a
      declining trend of BLL in Lucknow children when compared with those reported from
      other cities of India when leaded petrol was in practice. A national population
      based study is recommended to determine the prevalence of elevated BLLs after the
      phase-out of leaded-petrol. In addition, future studies on other sources of lead
      exposure in Lucknow are warranted for public health purposes.

PMID- 19161239
TI  - Fibroblast growth factor-2 deficiency affects hippocampal spine morphology, but
      not hippocampal catecholaminergic or cholinergic innervation.
AB  - The availability of fibroblast growth factor-2 (FGF-2) -deficient mice has
      permitted studying the role of endogenous FGF-2. Several studies have reported
      that neocortical but not hippocampal neurons are lost in FGF-2-deficient mice.
      Here, we show that neuronal densities within the basolateral amygdala are
      unaltered in FGF-2-/- mice. Moreover, we provide evidence that FGF-2 mutant mice
      display no obvious alterations in the catecholaminergic or cholinergic
      innervation of the hippocampus. With regard to the formation of dendritic spines,
      our studies reveal that endogenous FGF-2 is not essential for hippocampal
      spinogenesis; however, FGF-2 affects the length of individual spines. Such
      alterations in spine morphology may be related to disturbances in mental
      capacities or alterations in neuronal plasticity. Of interest, in this context,
      animal models of mental retardation develop no alterations in hippocampal spine
      densities, but display higher numbers of long dendritic spines. Thus, FGF-2 may
      also affect learning and memory by altering spine morphology.

PMID- 19161240
TI  - Estimating the spatiotemporal pattern of volumetric growth rate from fate maps in
      chick limb development.
AB  - Morphogenesis is achieved through volumetric growth of tissue at a rate varying
      over space and time. The volumetric growth rate of each piece of tissue reflects
      the behaviors of constituent cells such as cell proliferation and death. Hence,
      clarifying its spatiotemporal pattern accurately is a key to bridge between cell
      behaviors and organ morphogenesis. We here propose a new method to estimate the
      spatiotemporal pattern of volumetric growth rate from fate map data with limited
      resolution on space and time by using a mathematical model. We apply the method
      to chick wing data along the proximodistal axis, and find that the volumetric
      growth pattern is biphasic: it is spatially uniform in earlier stages (until
      stage 23), but in later stages the volumetric growth occurs approximately 4.5
      times as fast as in the distal region (within approximately 100 microm from the
      limb tip) than in the proximal region.

PMID- 19161241
TI  - C-myc as a modulator of renal stem/progenitor cell population.
AB  - The role of c-myc has been well-studied in gene regulation and oncogenesis but
      remains elusive in murine development from midgestation. We determined c-myc
      function during kidney development, organogenesis, and homeostasis by conditional
      loss of c-myc induced at two distinct phases of nephrogenesis, embryonic day (e)
      11.5 and e17.5. Deletion of c-myc in early metanephric mesenchyme (e11.5) led to
      renal hypoplasia from e15.5 to e17.5 that was sustained until adulthood (range,
      20-25%) and, hence, reproduced the human pathologic condition of renal
      hypoplasia. This phenotype resulted from depletion of c-myc-positive cells in cap
      mesenchyme, causing a approximately 35% marked decrease of Six2- and Cited1
      stem/progenitor population and of proliferation that likely impaired self
      renewal. By contrast, c-myc loss from e17.5 onward had no impact on late renal
      differentiation/maturation and/or homeostasis, providing evidence that c-myc is
      dispensable during these phases. This study identified c-myc as a modulator of
      renal organogenesis through regulation of stem/progenitor cell population.

PMID- 19161242
TI  - Comparative expression analysis of the neurogenins in Xenopus tropicalis and
      Xenopus laevis.
AB  - The Neurogenin (Ngn 1-3) family of proneural basic helix-loop-helix (bHLH)
      transcription factors are key regulators of vertebrate neurogenesis. In the
      developing vertebrate nervous system, the Ngns are essential for the commitment
      to a neuronal fate and participate in the specification of neuronal cell-type
      identity. Xenopus laevis is widely used as a model system to study the early
      events of vertebrate neurogenesis, however, only Ngnr-1, which is most closely
      related to the mammalian Ngn2, has been described and characterized. Presently,
      we describe a comparative expression analysis of the Ngn1-3 in X. tropicalis and
      X. laevis embryos. The Xenopus Ngns are present in overlapping, as well as unique
      regions of the nervous system starting at gastrula stages, suggesting distinct
      roles for this important family of transcriptional factors in the establishment
      of the amphibian nervous system.

PMID- 19161244
TI  - Small interfering peptide (siP) for in vivo examination of the developing lung
      interactonome.
AB  - To understand the role of reactive oxygen species in mechanosensory control of
      lung development a new approach to interfere with protein-protein interactions by
      means of a short interacting peptide was developed. This technology was used in
      the developing rodent lung to examine the role of NADPH oxidase (NOX), casein
      kinase 2 (CK2), and the cystic fibrosis transmembrane conductance regulator
      (CFTR) in stretch-induced differentiation. Interactions between these molecules
      was targeted in an in utero system with recombinant adeno-associated virus (rAAV)
      containing inserted DNA sequences that express a control peptide or small
      interfering peptides (siPs) specific for subunit interaction or phosphorylation
      predicted to be necessary for multimeric enzyme formation. In all cases only siPs
      with sequences necessary for a predicted normal function were found to interfere
      with assembly of the multimeric enzyme. A noninterfering control siP to
      nonessential regions or reporter genes alone had no effect. Physiologically, it
      was shown that siPs that interfered with the NOX-CFTR-CK2 complex that we call an
      "interactonome" affected markers of stretch-induced lung organogenesis including
      Wnt/beta-catenin signaling.

PMID- 19161245
TI  - The Caenorhabditis elegans heterochronic gene lin-14 coordinates temporal
      progression and maturation in the egg-laying system.
AB  - Heterochronic genes function to ensure the timing of stage-specific developmental
      events in C. elegans. Mutations in these genes cause certain developmental
      programs to be executed in a precocious or retarded manner. Canonical precocious
      (loss-of-function) and retarded (gain-of-function) mutations in the lin-14 gene
      lead to elimination or reiteration of larval stage-specific cellular events.
      Here, we describe a hypomorphic, missense allele of lin-14, sa485. lin-14(sa485)
      hermaphrodites pass through normal larval stages, but exhibit asynchrony between
      vulval and gonadal maturation in the L4 larval stage. We show that a subtly
      precocious morphogenetic event in the vulva disrupts tissue synchrony and is
      followed by retarded vulval eversion. Additionally, uterine uv1 cell
      differentiation is retarded in lin-14(sa485) animals that exhibit delayed vulval
      eversion. Together, these experiments outline a function for LIN-14 in
      coordinating the temporal progression of development, which is separable from its
      role in regulating stage-specific events during C. elegans postembryonic
      development.

PMID- 19161246
TI  - Tracking gene expression during zebrafish osteoblast differentiation.
AB  - The transcription factors RUNX2 and OSX have been shown to act sequentially to
      direct mammalian osteoblast differentiation. RUNX2 is required during the early
      stages of commitment and acts in part to activate Osx transcription. OSX and
      RUNX2 then act to direct transcription of bone matrix proteins. Here, we
      investigate the expression of these genes and others during zebrafish
      osteoblastogenesis. Using whole-mount in situ hybridization, we find that, during
      the formation of a given bone, the zebrafish homologues of mouse Runx2 (runx2a
      and runx2b) are typically expressed before the onset of osx. osx expression is
      usually followed by up-regulation of the bone matrix proteins, col1a2 and
      osteonectin. These results suggest that the mammalian pathway is conserved during
      development of the head and shoulder skeleton of zebrafish. We also analyze the
      expression of three atypical bone markers (tcf7, cvl2, and col10a1) in an effort
      to place them within this canonical hierarchy.

PMID- 19161247
TI  - Redistribution of xylan in maize cell walls during dilute acid pretreatment.
AB  - Developing processes for the conversion of biomass for use in transportation
      fuels production is becoming a critically important economic and engineering
      challenge. Dilute acid pretreatment is a promising technology for increasing the
      enzymatic digestibility of lignocellulosic biomass. However, a deeper
      understanding of the pretreatability of biomass is needed so that the rate of
      formation and yields of sugars can be increased. Xylan is an important
      hemicellulosic component of the plant cell wall and acts as a barrier to
      cellulose, essentially blocking cellulase action. To better understand xylan
      hydrolysis in corn stover, we have studied changes in the distribution of xylan
      caused by dilute acid pretreatment using correlative microscopy. A dramatic loss
      of xylan antibody signal from the center of the cell wall and an increase or
      retention of xylan at the plasma membrane interface and middle lamella of the
      cell were observed by confocal laser scanning microscopy (CLSM). We also observed
      a reduction in xylan fluorescence signal by CLSM that is generally consistent
      with the decrease in xylan content measured experimentally in the bulk sample,
      however, the compartmentalization of this xylan retention was not anticipated.

PMID- 19161248
TI  - Estrogenic and androgenic effects of municipal wastewater effluent on
      reproductive endpoint biomarkers in three-spined stickleback (Gasterosteus
      aculeatus).
AB  - Municipal wastewater treatment plants have been associated with the release of
      endocrine-disrupting chemicals, which consequently lead to alterations of
      reproductive function in aquatic organisms. The three-spined stickleback
      (Gasterosteus aculeatus) has quantifiable biomarkers for assessment of both
      estrogen (vitellogenin) and androgen (spiggin) activity, which makes this species
      very valuable in the research of endocrine disruption. The estrogenic and
      androgenic biomarkers were used for evaluating exposure effects of municipal
      wastewater effluent. We evaluated the effects of 17alpha-ethinylestradiol (EE2),
      17alpha-methyltestosterone (MT), and wastewater effluents on induction of
      vitellogenin and spiggin production, gonadosomatic index, hepatosomatic index,
      nephrosomatic index, plasma steroid levels, and histopathology. Adult female and
      male sticklebacks were exposed to 20 ng/L of EE2, 10 microg/L of MT, and
      wastewater effluent (10, 50, and 80% of original concentration) in a flow-through
      system for an exposure of one week and an extended exposure of four weeks.
      Chemical analyses of the steroids were done for verification of exposure
      concentrations and presence in the used wastewater. Our results show that
      municipal wastewater effluent exerts estrogenic action on three-spined
      stickleback as observed by elevated vitellogenin levels in exposed fish,
      corresponding to the effect seen in fish exposed to EE2. Furthermore, wastewater
      and EE2 exerted similar histopathological effects on testis of exposed fish.
      Although domestic effluent is suspected to have a high content of natural
      androgens, no obvious androgenic effect of wastewater was observed in the present
      study.

PMID- 19161249
TI  - Pro-inflammatory cytokine production in chagasic mothers and their uninfected
      newborns.
AB  - The levels of IFN-gamma, TNF-alpha, IL-10, and TGF-beta1 cytokines associated
      with Trypanosoma cruzi during pregnancy were determined by enzyme-linked
      immunosorbent assay (ELISA) in serum samples from peripheral, placental, and cord
      blood of chronic infected mothers with detectable and undetectable parasitemia,
      and in their uninfected newborns. Compared to uninfected pregnant women and
      mothers with undetectable parasitemia, the concentrations of IFN-gamma were
      higher at the 3 sites in mothers with detectable parasitemia. In these mothers
      and their newborns, the TNF-alpha concentrations were higher in the periphery and
      cord in comparison to serum samples from non-chagasic pregnant women. TNF-alpha
      levels were higher in newborns of mothers with detectable parasitemia than in
      newborns of mothers with undetectable parasitemia. IL-10 and TGF-beta1 levels at
      the 3 sites were unchanged and diminished, respectively, in samples from infected
      mothers with patent parasitemia in comparison with uninfected pregnant women.
      Cytokine concentrations did not change significantly in all samples from mothers
      with undetectable parasitemia; however, the concentration of TGF-beta1 was
      significantly reduced in their peripheral samples but significantly higher in the
      placenta in comparison with uninfected mothers and mothers with detectable
      parasitemia, respectively. These results suggest that elevated numbers of
      circulating parasites in vivo elicit production of pro-inflammatory cytokines
      that control congenital T. cruzi infection.

PMID- 19161253
TI  - Novel system to achieve one-pot modification of cargo molecules with
      oligoarginine vectors for intracellular delivery.
AB  - There is a growing number of reports showing the usefulness of cell-penetrating
      peptides (CPPs) including oligoarginines for intracellular delivery of
      macromolecules. Although the covalent attachment of the CPP segments to the cargo
      molecules is usually required to ensure effective delivery, conventional methods
      of conjugation need several manipulation steps that are often time-consuming and
      laborious. Here, we report a novel approach to allow easy modification of cargo
      molecules with oligoarginine CPPs. The key feature is the employment of
      oligoarginines (R8 and R12) equipped with a sulfosuccinimidylsuberyl moiety
      (BS(3)-R8 and -R12). One-pot modification is achieved simply by mixing BS(3)-R8
      and -R12 with cargos in an aqueous buffer. The usefulness of this approach was
      exemplified through the conjugate formation with Fab fragments of immunoglobulin
      G, amino-functionalized poly(ethylene glycol)s (amino-PEGs), and amino quantum
      dots (amino-QDs), yielding an efficient cellular uptake.

PMID- 19161254
TI  - Stereocontrolled synthesis of complicated oxacyclic compounds via platinum
      catalyzed [4 + 2]-cycloadditions and annulations of enynals with allylic
      alcohols.
AB  - We report stereoselective synthesis of tricyclic ketals through Pt(II)-catalyzed
      [4 + 2]-cycloaddition of benzopyrilium/1-en-3-ol functionalities. For nonaromatic
      enynals, we obtained distinct tricyclic oxacyclic ketones due to occurrence of a
      new annulation reaction. This work reports the first example that [4 + 2]
      cycloadducts are successfully intercepted from such functionalities in
      diversified approaches. The value of such cycloadditions and annulations are
      shown by their high diastereoselectivities and chemoselectivities.

PMID- 19161255
TI  - Postharvest ripening study of sweet lime (Citrus limettioides) in situ by volume
      localized NMR spectroscopy.
AB  - Spatially resolved NMR--especially volume-localized spectroscopy (VLS)is useful
      in various fields including clinical diagnosis, process monitoring, etc. VLS
      carries high significance because of its ability to identify molecular species
      and hence track molecular events. This paper reports the application of VLS at
      200 MHz to study the postharvest ripening of sweet lime ( Citrus limettioides )
      in situ, including a comparative study of normal and acetylene-mediated ripening.
      Localization to a cubic voxel of 64 microL was achieved with point-resolved
      spectroscopy (PRESS). Glucose, sucrose, fructose, and citric acid are found to be
      among the main constituents in the fruit. In the natural process, the sugar to
      acid ratio increases with ripening. Ethanol generation is seen to occur at a
      faster rate in acetylene-mediated ripening. Whereas NMR imaging experiments
      including parametric imaging (e.g., T(1) or T(2) maps) may be employed for
      "macro" monitoring of processes such as these, this work demonstrates that the
      molecular imprint of the process may be tracked noninvasively by VLS.

PMID- 19161257
TI  - Alternative donor-acceptor stacks from crown ethers and naphthalene diimide
      derivatives: rapid, selective formation from solution and solid state grinding.
AB  - The atypical 1:2 complexation between an electron-rich crown ether host and
      electron-deficient naphthalene diimide-based guests led to the formation of
      alternative donor-acceptor (ADA) stacks. The ADA stacks can be expediently
      obtained in high yield as polycrystalline aggregates from solution. More
      remarkably, the high degree of organization has also been realized in a simple
      solid-to-solid mechanical grinding process. The solid-state structures have been
      verified by solid-state NMR spectroscopy, single crystal, and powder X-ray
      diffraction analysis. The current findings not only provide convenient ways of
      obtaining novel donor-acceptor stacks involving a macrocyclic host but also
      represent an important step in transferring electroactive host-guest systems from
      solution to the solid state.

PMID- 19161258
TI  - Method for the determination of Pd-catalyst residues in active pharmaceutical
      ingredients by means of high-energy polarized-beam energy dispersive X-ray
      fluorescence.
AB  - In medicinal chemistry, Pd is perhaps the most-widely utilized precious metal, as
      catalyst in reactions which represent key transformations toward the synthesis of
      new active pharmaceutical ingredients (APIs). The disadvantage of this metal
      catalyzed chemistry is that expensive and toxic metal residues are invariably
      left bound to the desired product. Thus, stringent regulatory guidelines exist
      for the amount of residual Pd that a drug candidate is allowed to contain. In
      this work, a rapid and simple method for the determination of Pd in API samples
      by high-energy polarized-beam energy dispersive X-ray fluorescence spectrometry
      has been developed and validated according to the specification limits of current
      legislation (10 mg kg(-1) Pd) and the International Conference on Harmonisation
      of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH
      guidelines). Sample and calibration standards preparation includes a first step
      of homogenization and then, in a second step, the pressing of the powdered
      material into pellets without any chemical treatment. The use of several
      synthetic calibration standards made of cellulose to simulate the API matrix
      appears to be an effective means to obtain reliable calibration curves with a
      good spread of data points over the working range. With the use of the best
      measuring conditions, the limit of detection (0.11 mg kg(-1) Pd) as well as the
      limit of quantitation (0.37 mg kg(-1) Pd) achieved meet rigorous requirements.
      The repeatability of the XRF measurement appeared to be less than 2%, while the
      precision of the whole method was around 7%. Trueness was evaluated by analyzing
      spiked API samples at the level of the specification limit and calculating the
      recovery factor, which was better than 95%. To study the applicability of the
      developed methodology for the intended purpose, three batches of the studied API
      were analyzed for their Pd content, and the attained results were comparable to
      those obtained by the daily routine method (acid digestion plus atomic
      spectroscopy) used in most pharmaceutical laboratories.

PMID- 19161259
TI  - Quantitative fluorescence correction incorporating Forster resonance energy
      transfer and its use for measurement of hybridization efficiency on microarrays.
AB  - Fluorescence detection using two spectrally distinct fluorophores has long been
      used for the determination of the relative abundance of biomolecules, but overlap
      between the fluorescence spectra of each fluorophore can result in nonradiative
      Forster resonance energy transfer (FRET) and distorting the signals detected by
      fluorescence channels. Thus conventional methods for quantifying the relative
      abundance of fluorophores by fluorescence emission will not be accurate if FRET
      can occur. In this paper we report the development of a quantitative fluorescence
      correction method incorporating FRET to measure the relative abundance of
      fluorophores in dual-labeling experiments. The quantitative fluorescence
      correction method incorporating FRET is accurate, comprehensive, and convenient
      for the measurement of the relative abundance of fluorophores in dual-labeling
      experiments and can also correct the FRET distortion and provide accurate,
      quantitative, and convenient measurement of the hybridization efficiencies on
      microarrays.

PMID- 19161260
TI  - A novel cyclometalated dimeric iridium complex, [(dfpbo)2Ir]2 [dfpbo = 2-(3,5
      difluorophenyl)benzoxazolato-N,C2'], containing an unsupported Ir(II)-Ir(II)
      bond.
AB  - An unusual iridium complex, [(dfpbo)(2)Ir](2) [dfpbo = 2-(3,5
      difluorophenyl)benzoxazolato-N,C(2')], which is the first dimeric iridium complex
      composed of two bis-cyclometalated Ir(II) structures connected by an unsupported
      Ir(II)-Ir(II) bond, has been synthesized and fully characterized. Under mild
      conditions of neutral pH at room temperature, this complex dissociated
      spontaneously to form the stable radical [Ir(dfpbo)(2)]*.

PMID- 19161261
TI  - Heterojunction photovoltaics using printed colloidal quantum dots as a
      photosensitive layer.
AB  - We demonstrate a bilayer photovoltaic device consisting of a heterojunction
      between colloidal cadmium selenide (CdSe) quantum dots (QDs) and a wide band gap
      organic hole-transporting thin film of N,N'-diphenyl-N,N'-bis(3
      methylphenyl)[1,1'-biphenyl]-4,4'-diamine (TPD) molecules. The active light
      absorbing film of QDs is nondestructively printed onto TPD using microcontact
      stamping. Indium-tin-oxide (ITO) provides the top contact. The resulting device
      structure can accommodate different size QDs, produces an exceptionally large
      open circuit voltage (0.8 V) for an architecture with symmetric electrodes, and
      yields an internal quantum efficiency of 10% at the first QD absorption peak.

PMID- 19161262
TI  - In situ reduction in photocycloadditions: a method to prevent secondary
      photoreactions.
AB  - Secondary photoreactions are a common cause for the low yields often observed in
      photochemical reactions, preventing their widespread deployment in synthesis. In
      situ reductions which remove the chromophore from the product as it is formed
      provide a convenient method to prevent these secondary photoreactions.

PMID- 19161263
TI  - Unique effect of coordination of an alkene moiety in products on ruthenium
      catalyzed chemoselective C-H alkenylation.
AB  - Ruthenium-catalyzed alkenylation of 2'-alkoxyacetophenones with alkenylboronates
      provides ortho C-H alkenylation products without sacrificing an ether functional
      group at the other ortho position. Both excellent chemoselectivity and high
      product yields are achieved with an aryloxo ruthenium complex. The effective
      suppression of the C-O bond cleavage was attained by coordination of the alkenyl
      moiety in the C-H alkenylation product to the ruthenium center.

PMID- 19161264
TI  - Water adsorption on the stoichiometric (001) and (010) surfaces of
      hydroxyapatite: a periodic B3LYP study.
AB  - H2O adsorption on hexagonal hydroxyapatite (001) and (010) stoichiometric
      surfaces has been studied at B3LYP level with a localized Gaussian basis set of
      polarized double-zeta quality using the periodic CRYSTAL06 code. Because four
      Ca2+ cations are available at both surfaces, the considered H2O coverages span
      the 1/4<or=theta<or=5/4 range. The affinity of both HA surfaces for H2O is large:
      on the (001) surface, H2O adsorbs molecularly (binding energies BE approximately
      80 kJ mol(-1) per adsorbed molecule), whereas it dissociates on the (010)
      surface, giving rise to new surface terminations (CaOwHw and POHw). The highly
      negative reaction energy for H2O dissociation (between -250 and -320 kJ mol(-1)
      per adsorbed H2O molecule) strongly suggests that the pristine (010) surface "as
      cut" from the hydroxyapatite bulk cannot survive in aqueous environment.
      Conversely, on the reacted surface, H2O adsorbs molecularly with BE similar to
      those computed for the (001) surface. The B3LYP BEs have been contrasted to the
      experimental water adsorption enthalpies measured by microcalorimetry on
      polycrystalline hydroxyapatite samples, showing a fairly good agreement and
      supporting the suggestion that H2O vapor adsorbs on the already reacted (010)
      crystalline faces. Harmonic B3LYP vibrational features of adsorbed H2O show, when
      compared to modes of the gas-phase H2O, a hypsochromic shift of the HOH bending
      mode (Deltadelta(HOH)=49 cm(-1)) and a bathochromic shift of the OH stretching
      modes larger than 1700 cm(-1) (Deltanu(OH)=427 cm(-1)), which are both in good
      agreement with literature experimental data.

PMID- 19161265
TI  - Hydrophobic films by atmospheric plasma curing of spun-on liquid precursors.
AB  - Hydrophobic coatings have been produced on glass and acrylic samples by using a
      low-temperature atmospheric pressure plasma to polymerize liquid
      fluoroalkylsilane precursors. The fluoroalkylsilane precursor was dissolved in
      isooctane and spun onto the substrate at 550 rpm. The sample was then exposed to
      the reactive species generated from a nitrogen plasma. The plasma was operated
      with 2.3 vol % N2 in helium at 7.4 W/cm2 at a radio frequency of 27.12 MHz. The
      total and polar component of the coating's surface energy was found to equal 11.0
      and 1.2 dyn/cm, respectively. Average water contact angles of 110 degrees and 106
      degrees were measured on the coated glass and acrylic surfaces, respectively. X
      ray photoelectron spectroscopy revealed that, after treatment, the fluoroalkyl
      ligands remained intact on the Si atoms, with a F/C atomic ratio of 2.23.

PMID- 19161267
TI  - Synthesis of hollow-structured nano- and microspheres from pectin in a
      nanodroplet emulsion.
AB  - Hollow-structured nano- and microspheres with diameters ranging from 24 microm to
      160 nm were successfully produced from chemically modified pectin (Ma-Pec)
      through a two-step synthesis. In a first step, the Pec was modified with glycidyl
      methacrylate (GMA) in a heterogeneous phase system, indeed consisting of water
      soluble Pec and water-insoluble GMA, via an interfacial reaction at the interface
      of the GMA-water phase system after 12 h under continuous stirring of 1000 rpm at
      60 degrees C. In a second step, the spheres were prepared in a water-in-benzyl
      alcohol nanodroplet emulsion at 12000 rpm under a bubbling stream of nitrogen in
      the presence of sodium persulfate, as initiator, and TEMED, as catalytic agent.
      FT-IR spectra revealed that the vinyl groups (CC) coming from the GMA were
      attached onto backbone of the polysaccharide. 13C-CP/MAS NMR spectra demonstrated
      that the spheres were formed via carbon-carbon pi-bonds on Ma-Pec in the water
      phase, for the duration of the dispersion stage. The dark center (an empty core)
      and edge of the hollow spheres could be easily identified by SEM micrographs.
      This type of polymer structure represents a class of unique material with
      particular importance in terms of state-of the-art applications in both nano- and
      microencapsulation of drugs, for example, protection shields of biologically
      active agents.

PMID- 19161266
TI  - Comparison of the different types of surfactants for the effect on activity and
      structure of soybean peroxidase.
AB  - In the pH 2.6 and 5.2 systems, soybean peroxidase (SBP) (isoelectric point, pI
      3.9) has positive and negative charge, respectively. In order to acquire detailed
      knowledge on the role played by electrostatics in the denaturation of proteins, a
      comparison of anionic surfactant sodium dodecyl sulfate (SDS), nonionic
      surfactant nonaethylene glycol monododecyl ether [C12H25O(CH2CH2O)9H] (AEO9), and
      cationic surfactant cetyltrimethylammonium bromide (CTAB) for the influences on
      the activity and structure of soybean peroxidase (SBP) was carried out by
      measuring the activity, far-UV circular dichrosm, fluorescence, and electronic
      absorption spectra of SBP in the pH 2.6 and 5.2 systems at 30 degrees C. In the
      pH 2.6 systems, the interaction of SDS with SBP results in an increase in the
      fluorescence intensity with a red shift of the emission maximum of the tryptophan
      fluorescence and a blue shift of the Soret band. In the meantime, the alpha-helix
      of SBP is unfolded and the activity of SBP is lost irreversibly. In pH 5.2
      systems, the fluorescence spectra features of SBP are similar to those in pH 2.6
      systems with increasing SDS concentration, but a red shift of Soret band as well
      as an alteration of the tertiary structure of SBP occurs, and the lost activity
      is recoverable. The electrostatic interactions between SBP and SDS play an
      important role in the denaturation of SBP. The effects of AEO9 and CTAB in pH 2.6
      and 5.2 systems on the activity and spectral features of SBP are similar to that
      of SDS in pH 5.2 systems, but AEO9 is prone to unfold the beta-sheet of SBP in pH
      2.6 systems. The electrostatic interactions of CTAB with SBP are not the primary
      elements for denaturation of SBP, which distinctly differ from those of SDS.
      These results can be useful with respect to wide applications of the surfactants
      in the separation and purification of proteins.

PMID- 19161269
TI  - Submolecular electronic mapping of single cysteine molecules by in situ scanning
      tunneling imaging.
AB  - We have used L-cysteine (Cys) as a model system to study the surface electronic
      structures of single molecules at the submolecular level in aqueous buffer
      solution by a combination of electrochemical scanning tunneling microscopy (in
      situ STM), electrochemistry including voltammetry and chronocoulometry, and
      density functional theory (DFT) computations. Cys molecules were assembled on
      single-crystal Au(110) surfaces to form a highly ordered monolayer with a
      periodic lattice structure of c(2x2) in which each unit contains two molecules;
      this conclusion is confirmed by the results of calculations based on a slab model
      for the metal surface. The ordered monolayer offers a platform for submolecular
      scale electronic mapping that is an issue of fundamental interest but remains a
      challenge in STM imaging science and surface chemistry. Single Cys molecules were
      mapped as three electronic subunits contributed mainly from three chemical
      moieties: thiol (-SH), carboxylic (-COOH), and amine (-NH2) groups. The contrasts
      of the three subunits depend on the environment (e.g., pH), which affects the
      electronic structure of adsorbed species. From the DFT computations focused on
      single molecules, rational analysis of the electronic structures is achieved to
      delineate the main factors that determine electronic contrasts in the STM images.
      These factors include the molecular orientation, the chemical nature of the
      elements or groups in the molecule, and the interaction of the elements with the
      substrate and tip. The computational images recast as constant-current-height
      profiles show that the most favorable molecular orientation is the adsorption of
      cysteine as a radical in zwitterionic form located on the bridge between the
      Au(110) atomic rows and with the amine and carboxyl group toward the solution
      bulk. The correlation between physical location and electronic contrast of the
      adsorbed molecules was also revealed by the computational data. The present study
      shows that cysteine packing in the adlayer on Au(110) from the liquid environment
      is in contrast to that from the ultrahigh-vacuum environment, suggesting solvent
      plays a role during molecular assembly.

PMID- 19161268
TI  - Effect of molecular structure of cationic surfactants on biophysical interactions
      of surfactant-modified nanoparticles with a model membrane and cellular uptake.
AB  - The aim of this study was to test the hypothesis that the molecular structure of
      cationic surfactants at the nanoparticle (NP) interface influences the
      biophysical interactions of NPs with a model membrane and cellular uptake of NPs.
      Polystyrene NPs (surfactant-free, 130 nm) were modified with cationic
      surfactants. These surfactants were of either dichained
      (didodecyldimethylammonium bromide [DMAB]) or single-chained
      (cetyltrimethylammonium bromide [CTAB] and dodecyltrimethylammonium bromide
      [DTAB]) forms, with the latter two having different hydrophobic chain lengths.
      Biophysical interactions of these surfactant-modified NPs with an endothelial
      cell model membrane (EMM) were studied using a Langmuir film balance. Changes in
      surface pressure (SP) of EMM as a function of time following interaction with NPs
      and in the compression isotherm (pi-A) of the lipid mixture of EMM in the
      presence of NPs were analyzed. Langmuir-Schaeffer (LS) films, which are EMMs that
      have been transferred onto a suitable substrate, were imaged by atomic force
      microscopy (AFM), and the images were analyzed to determine the mechanisms of the
      NP-EMM interaction. DMAB-modified NPs showed a greater increase in SP and a shift
      toward higher mean molecular area (mmA) than CTAB- and DTAB-modified NPs,
      indicating stronger interactions of DMAB-modified NPs with the EMM. However,
      analysis of the AFM phase and height images of the LS films revealed that both
      DMAB- and CTAB-modified NPs interacted with the EMM but via different mechanisms:
      DMAB-modified NPs penetrated the EMM, thus explaining the increase in SP, whereas
      CTAB-modified NPs anchored onto the EMM's condensed lipid domains and hence did
      not cause any significant change in SP. Human umbilical vein endothelial cells
      showed greater uptake of DMAB- and CTAB-modified NPs than of DTAB-modified or
      unmodified NPs. We conclude that (i) the dichained and single-chained cationic
      surfactants on NPs have different mechanisms of interaction with the model
      membrane and that (ii) NPs that demonstrate greater biophysical interactions with
      the membrane also show greater cellular uptake. Biophysical interactions of NPs
      with a model membrane thus could be effectively used for developing nanocarriers
      with optimized surface properties for drug delivery and imaging applications.

PMID- 19161270
TI  - Effects of shear and charge on the microphase formation of P123 polymer in the
      SBA-15 synthesis investigated by mesoscale simulations.
AB  - Mesoscale simulation was performed to investigate the dynamical structural
      behavior of the pluronic P123 block copolymer in the synthesis of mesoporous SBA
      15. Shear is introduced to represent stirring in the actual experiment, and a
      weak charge is included to simulate the acidic conditions in the synthesis. Under
      shear, with the increase in weak charge in the PEO [poly(ethylene oxide)] block,
      the template forms more ordered hexagonal phases, and the pore sizes of the
      cylindrical hydrophobic PPO [poly(propylene oxide)] blocks decrease. The
      structural factor shows three types of water molecules in the mesoscale
      aggregates, including bulk water in the solution, bound water around the
      hydrophilic PEO corona, and trapped water in the hydrophobic PPO core. When 1,3,5
      trimethyl-benzene (TMB) is added to the system as a swelling agent, expanded
      hexagonal phases are formed, and the density mapping of TMB shows that the TMB
      molecules are mainly located in the hydrophobic PPO cores. In configurations with
      spherical micelles, although bimodally dispersed spheres are observed, the face
      centered cubic (fcc) packing of the micelles hardly changes with the addition of
      TMB. In agreement with experimental results, the simulations show that the shear
      and the weak charge are essential to the formation of hexagonal templates in the
      copolymer. Mesoscopic simulations complement experimental investigations on the
      morphology changes of amphiphilic polymer in template syntheses and can provide
      important guidance for further experiments.

PMID- 19161271
TI  - Method for determining double-bond positions in mixtures of linear olefins.
AB  - We describe a new method for estimating the positions of double bonds in mixtures
      of linear olefins longer than octene. The method requires about a gram of olefin
      and a 5-10 min reaction catalyzed by a homogeneous metathesis catalyst. The
      carbon number distribution of the product mixture, as determined by gas
      chromatography, depends upon the distribution of double-bond isomers in the
      starting mixture. We describe a computer algorithm for using the final carbon
      number distribution to determine the locations of double bonds in the starting
      mixture. Examples are based on tetradecenes, hexadecenes, and octadecenes.

PMID- 19161272
TI  - Interpolyelectrolyte complexes between starlike and linear macromolecules: a
      structural model for nonviral gene vectors.
AB  - Molecular dynamics simulations are used to probe the structural organization of
      nonstoichiometric interpolyelectrolyte complexes (IPECs) formed by oppositely
      charged starlike and linear polyelectrolytes (PEs) in dilute aqueous solution. We
      demonstrate that undercompensated star-IPEC consists of a denser coacervate core
      and a charged starlike corona. Two distinctive populations of star branches
      completely embedded in a coacervate core and stretched in a lyophilizing corona
      are found. The scaling arguments support the stability of IPEC with partitioned
      star branches.

PMID- 19161273
TI  - Soft hydrogels from nanotubes of poly(ethylene oxide)-tetraphenylalanine
      conjugates prepared by click chemistry.
AB  - A new poly(ethylene oxide)-tetraphenylalanine polymer-peptide conjugate has been
      prepared via a "click" reaction between an alkyne-modified peptide and an azide
      terminated PEO oligomer. Self-assembled nanotubes are formed after dialysis of a
      THF solution of this polymer-peptide conjugate against water. The structure of
      these nanotubes has been probed by circular dichroism, IR, TEM, and SAXS. From
      these data, it is apparent that self-assembly involves the formation of
      antiparallel beta-sheets and pi-pi-stacking. Nanotubes are formed at
      concentrations between 2 and 10 mg mL(-1). Entanglement between adjacent
      nanotubes occurs at higher concentrations, resulting in the formation of soft
      hydrogels. Gel strength increases at higher polymer-peptide conjugate
      concentration, as expected.

PMID- 19161274
TI  - Aziridination of C60 with simple amides and catalytic rearrangement of the
      aziridinofullerenes to azafulleroids.
AB  - The selective formation of aziridinofullerene and azafulleroid, which are isomers
      of the fullerene derivatives-introduced N(1) unit, is achieved. The ionic
      aziridination is a very convenient and risk-free procedure compared with the
      conventional method with azides as nitrogen sources, and gives
      aziridinofullerenes from various readily available amides (carbamates, ureas,
      carboxamides, and phosphamides). For example, benzyl carbamate was chlorinated by
      tert-butyl hypochlorite (tert-BuOCl) and then reacted with C(60) in the presence
      of base to give N-benzyloxycarbonyl aziridinofullerene exclusively and without
      formation of its isomer, an azafulleroid. The reaction enabled the synthesis of
      functional fullerene derivatives having a trialkoxysilyl group and an amino acid
      moiety. Azafulleroids were obtained through the rearrangement of corresponding
      aziridinofullerenes by using the combination of a chloramine catalyst and MS4A.
      Among other chloramines used, chloramine B (CB) showed superior ability as a
      catalyst in the rearrangement. It was found that MS4A functions as a Lewis acid
      in the reaction.

PMID- 19161275
TI  - Biosynthetic gene-based secondary metabolite screening: a new diterpene, methyl
      phomopsenonate, from the fungus Phomopsis amygdali.
AB  - The presence of the geranylgeranyl diphosphate synthase (GGS) gene is a common
      feature of gene clusters for diterpene biosynthesis. We demonstrated
      identification of a diterpene gene cluster using homology-based PCR of GGS genes
      and the subsequent genome walking in the fungus Phomopsis amygdali N2. Structure
      determination of a novel diterpene hydrocarbon phomopsene provided by enzymatic
      synthesis with the recombinant terpene synthase PaPS and screening of fungal
      broth extracts with reference to characteristic NMR signals of phomopsene allowed
      us to isolate a new diterpene, methyl phomopsenonate. The versatility of the gene
      based screening of unidentified diterpenes is discussed in regard to fungal
      genomic data.

PMID- 19161277
TI  - Palladium-controlled beta-selective glycosylation in the absence of the C(2)
      ester participatory group.
AB  - The development of a new glycosylation method for the stereoselective synthesis
      of beta-glycosides in the absence of the traditional C(2)-ester neighboring group
      effect is described. This process relies on the ability of the cationic palladium
      catalyst, Pd(PhCN)(2)(OTf)(2) generated in situ from Pd(PhCN)(2)Cl(2) and AgOTf,
      to direct beta-selectivity. The new glycosylation reaction is highly beta
      selective and proceeds under mild conditions with 1-2 mol % of catalyst loading.
      This beta-glycosylation method has been applied to a number of glucose donors
      with benzyl, allyl, and p-methoxybenzyl groups incorporated at the C(2)-position
      as well as tribenzylated xylose and quinovose donors to prepare various
      disaccharides and trisaccharides with good to excellent beta-selectivity.
      Mechanistic studies suggest that the major operative pathway is likely to proceed
      via a seven-membered ring intermediate, wherein the cationic palladium complex
      coordinates to both the C(1)-imidate nitrogen and C(2)-oxygen of the
      trichloroacetimidate donor. Formation of this seven-membered ring intermediate
      directs the selectivity, leading to the formation of beta-glycosides.

PMID- 19161276
TI  - Synthesis of conformationally preorganized and cell-permeable guanidine-based
      gamma-peptide nucleic acids (gammaGPNAs).
AB  - A general method for preparing optically pure guanidine-based gamma-peptide
      nucleic acid (gammaGPNA) monomers for all four natural nucleobases (A, C, G, and
      T) is described. These second-generation gammaGPNAs differ from the first
      generation GPNAs in that the guanidinium group is installed at the gamma- instead
      of the alpha-position of the N-(2-aminoethyl)glycine backbone unit. This
      positional switch enables GPNAs to be synthesized from relatively cheap L- as
      opposed to D-amino acids. Unlike their alpha-predecessors, which are randomly
      folded, gammaGPNAs prepared from L-amino acids are preorganized into a right
      handed helix and bind to DNA and RNA with exceptionally high affinity and
      sequence selectivity and are readily taken up by mammalian cells.

PMID- 19161278
TI  - Discovery of the first selective inhibitor of excitatory amino acid transporter
      subtype 1.
AB  - The discovery of the first class of subtype-selective inhibitors of the human
      excitatory amino acid transporter subtype 1 (EAAT1) and its rat orthologue GLAST
      is reported. An opening structure-activity relationship of 25 analogues is
      presented that addresses the influence of substitutions at the 4- and 7-positions
      of the parental skeleton 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3
      carbonitrile. The most potent analogue 1o displays high nanomolar inhibitory
      activity at EAAT1 and a >400-fold selectivity over EAAT2 and EAAT3, making it a
      highly valuable pharmacological tool.

PMID- 19161279
TI  - A series of 2,4-disubstituted quinolines as a new class of allosteric enhancers
      of the adenosine A3 receptor.
AB  - The adenosine receptor subfamily consists of the adenosine A(1), A(2A), A(2B),
      and A(3) receptors, which are localized in a variety of tissues throughout the
      human body. It is, therefore, a challenge to develop receptor specific ligands
      with improved tissue selectivity. Allosteric modulators could have these
      therapeutic advantages over orthosteric ligands. In the present study, a series
      of 2,4-disubstituted quinolines were synthesized on the basis of the structure of
      LUF6000 (34). Compound 27 (LUF6096) was able to allosterically enhance agonist
      binding to a similar extent as 34. In addition, this new compound showed low, if
      any, orthosteric affinity for any of the adenosine receptors. In a functional
      assay, compound 27 showed improved activity in comparison to 34, as it increased
      both the intrinsic efficacy and the potency of the reference agonist Cl-IB-MECA
      at the human adenosine A(3) receptor.

PMID- 19161280
TI  - Salt-induced aggregation of polyelectrolyte-amphiphilic dendron complexes in THF
      solutions.
AB  - Complexes were prepared by complexing amphiphilic dendrons (first, second, and
      third generations) with an oppositely charged polyelectrolyte through ionic
      interaction. Their chemical structure can be confirmed by nuclear magnetic
      resonance spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FT-IR),
      and elemental analysis (EA). All of the complexes were investigated with respect
      to their aggregation behavior. Under the inducement of salt addition in THF, they
      showed interesting self-assembly behavior, forming micelles and vesicles
      depending on the amount of the salt. The formation of these self-assemblies has
      been proven by dynamic light scattering (DLS), static light scattering (SLS), and
      electron microscopy (EM) as well as atomic force microscopy (AFM). Dilution
      experiments showed that the formed vesicles have good stability against dilution
      as well as polyelectrolyte behavior. The formation of micelle and vesicle
      aggregates described in this article is probably based on the entropy effect and
      the shape transformation of building blocks caused by salt addition.

PMID- 19161281
TI  - Liquid crystal alignment on ion-beam-treated polyimide with a long alkyl side
      chain: near edge X-ray absorption fine structure spectroscopy analysis.
AB  - Liquid crystal alignment on ion-beam-treated polyimides with a long alkyl side
      chain was investigated using near edge X-ray absorption fine structure (NEXAFS)
      spectroscopy. The long alkyl side chains and the asymmetric distribution and
      orientational order of the pi-bonds of the polyimide surface can be determined by
      analyzing the angular dependent resonance intensities of the NEXAFS measurements.
      Herein, we demonstrate that the pretilt angle of the LC cell made by our method
      decreases as more long alkyl side chains are destroyed. Additionally, the tilt
      direction of the LC molecules can be determined from the asymmetric distribution
      of pi-bonds of the polyimide created by the ion beam irradiation.

PMID- 19161283
TI  - Glycolipids and benzylammonium lipids as novel antisepsis agents: synthesis and
      biological characterization.
AB  - New glycolipids and a benzylammonium lipid were rationally designed by varying
      the chemical structure of a D-glucose-derived hit compound active as lipid A
      antagonist. We report the synthesis of these compounds, their in vitro activity
      as lipid A antagonists on HEK cells, and the capacity to inhibit LPS-induced
      septic shock in vivo. The lack of toxicity and the good in vivo activity suggest
      the use of some compounds of the panel as hits for antisepsis drug development.

PMID- 19161284
TI  - A comparative (13)C NMR study of local ordering in a homologous series of bent
      core liquid crystals.
AB  - A 13C NMR study is carried out in a number of banana-shaped molecules belonging
      to a homologous series. The derivatives contain chlorine or bromine
      substituent(s) in the center ring of 1,3-phenylene bis[4'-alkenyloxy biphenyl]-4
      carboxylate (nPBBC), and different terminal chain lengths are systematically
      compared in terms of their local order parameters and their ability to form an
      aligned nematic phase in the NMR magnet. The chemical shift anisotropy tensors
      measured from nPBBC by fitting the 13C powder patterns are now extensively used
      on these molecules to interpret their observed 13C chemical shifts in the nematic
      phase. The bend angles are estimated as a function of temperature in two members
      of the nPBBC series. Conformation twists in the bent-core region inferred from
      the local molecular biaxial paramters are discussed.

PMID- 19161282
TI  - Different intermediate populations formed by tazobactam, sulbactam, and
      clavulanate reacting with SHV-1 beta-lactamases: Raman crystallographic evidence.
AB  - Tazobactam, sulbactam, and clavulanic acid are the only beta-lactamase inhibitors
      in clinical use. Comparative inhibitory activities of clavulanic acid, sulbactam,
      and tazobactam against clinically important beta-lactamases conclude that
      tazobactam is superior to both clavulanic acid and sulbactam. Thus far, the
      majority of explanations for this phenomenon have relied on kinetic studies,
      which report differences in the ligands' apparent dissociation constants and
      number of turnovers before inactivation. Due their innate limitations, these
      investigations do not examine the identity of intermediates on the reaction
      pathway and relate them to the efficacy of the inhibitors. In the present study,
      the reactions between the three inhibitors and SHV-1 beta-lactamase have been
      examined in single crystals using a Raman microscope. The results show that
      tazobactam forms a predominant population of trans-enamine, a chemically inert
      species, with SHV-1, while clavulanate and sulbactam form a mixture of trans
      enamine and two labile species, the cis-enamine and imine. The same reactions are
      then reexamined using a deacylation-deficient variant, SHV E166A, that has been
      used to trap acyl-enzyme intermediates for X-ray crystallographic analysis. Our
      Raman data show that significant differences exist between the wild-type and SHV
      E166A acyl-enzyme populations. Namely, compared to SHV-1, sulbactam shows
      significantly smaller populations of cis-enamine and imine in the E166A variant,
      while clavulanate exists almost exclusively as trans-enamine in the E166A active
      site. Using clavulanate as an example, we also show that Raman crystallography
      can provide novel information on the presence of multiple conformers or tautomers
      for intermediates within a complex reaction pathway. These insights caution
      against the interpretation of experimental data obtained with deacylation
      deficient beta-lactamases to make mechanistic conclusions about inhibitors within
      the enzyme.

PMID- 19161285
TI  - Interaction of monotopic membrane enzymes with a lipid bilayer: a coarse-grained
      MD simulation study.
AB  - Monotopic membrane proteins bind tightly to cell membranes but do not generally
      span the lipid bilayer. Their interactions with lipid bilayers may be studied via
      coarse-grained molecular dynamics (CG-MD) simulations. Understanding such
      interactions is important as monotopic enzymes frequently act on hydrophobic
      substrates, while X-ray structures rarely provide direct information about their
      interactions with membranes. CG-MD self-assembly simulations enable prediction of
      the orientation and depth of insertion into a lipid bilayer of a monotopic
      protein, and also of the interactions of individual protein residues with lipid
      molecules. The CG-MD method has been evaluated via comparison with extended (>30
      ns) atomistic simulations of monoamine oxidase, revealing good agreement between
      the results of coarse-grained and atomistic simulations. CG-MD simulations have
      been applied to a set of 11 monotopic proteins for which three-dimensional
      structures are available. These proteins may be divided into two groups on the
      basis of the results of the simulations. One group consists of those proteins
      which are inserted into the lipid bilayer to a limited extent, interacting mainly
      at the phospholipid-water interface. The second group consists of those which are
      inserted more deeply into the bilayer. Those monotopic proteins which are
      inserted more deeply cause significant local perturbation of bilayer properties
      such as bilayer thickness. Deeper insertion seems to correlate with a greater
      number of basic residues in the "foot" whereby a monotopic protein interacts with
      the membrane.

PMID- 19161286
TI  - KAP, the accessory subunit of kinesin-2, binds the predicted coiled-coil stalk of
      the motor subunits.
AB  - Kinesin-2 is an anterograde motor involved in intraflagellar transport and
      certain other intracellular transport processes. It consists of two different
      motor subunits and an accessory protein KAP (kinesin accessory protein). The
      motor subunits were shown to bind each other through the coiled-coil stalk
      domains, while KAP was proposed to bind the tail domains of the motor subunits.
      Although several genetic studies established that KAP plays an important role in
      kinesin-2 functions, its exact role remains unclear. Here, we report the results
      of a systematic analysis of the KAP binding sites by using recombinant Drosophila
      kinesin-2 subunits as well as the endogenous proteins. These show that at least
      one of the coiled-coil stalks is sufficient to bind the N-terminal region of
      DmKAP. The soluble complex involving the recombinant kinesin-2 fragments is
      reconstituted in vitro at high salt concentrations, suggesting that the
      interaction is primarily nonionic. Furthermore, independent distant homology
      modeling indicated that DmKAP may bind along the coiled-coil stalks through a
      combination of predominantly hydrophobic interactions and hydrogen bonds. These
      observations led us to propose that KAP would stabilize the motor subunit
      heterodimer and help assemble a greater kinesin-2 complex in vivo.

PMID- 19161287
TI  - Reaction of hydrated electrons with guanine derivatives: tautomerism of
      intermediate species.
AB  - Here, we show that two tautomers are produced by the protonation of the guanine
      electron adduct. The fate of electron adducts of a variety of substituted
      guanosines was investigated by radiolytic methods and addressed computationally
      by means of time-dependent DFT (TD-B3LYP/6-311G**//B1B95/6-31+G**) calculations.
      The reaction of e(aq-) with guanosine and 1-methylguanosine produces two
      transient species, whereas the reaction with N2-ethylguanosine and N2,N2
      diethylguanosine produces only one. The two short-lived intermediates, which show
      a substantial difference in their UV-visible spectra, are recognized to be two
      purine tautomers (i.e., iminic 18 and aminic 19 forms). The tautomerization 18 -
      > 19 occurs with a rate constant of ca. 1.5 x 106 s(-1) , and theory suggests
      that it is a water-assisted process.

PMID- 19161288
TI  - Chitin-incorporated poly(ethylene oxide)-based nanocomposite electrolytes for
      lithium batteries.
AB  - Nanocomposite polymer electrolytes (NCPE), with different proportions of
      poly(ethylene oxide)/LiClO(4)/chitin were prepared by a hot press method.
      Nanochitin, a biopolymer, poly(beta-(1-->4)-N acetyl-d-glucosamine) was
      incorporated as a filler in poly(ethylene oxide) (PEO). The ionic conductivity of
      the composite polymer electrolytes was enhanced by one order upon addition of
      nanochitin. The lithium transference number, t(Li)(+), was increased from 0.24 to
      0.51 upon chitin addition. The membranes were subjected to scanning electron
      microscopy, thermogravimetric-differential thermal analysis, differential
      scanning calorimetry, ionic conductivity, and Fourier transform infrared (FTIR)
      spectroscopy analysis. The free volume V(f) was probed by positron annihilation
      lifetime spectroscopy studies at 30 degrees C. Li/NCPE/Li symmetric cells were
      assembled, and the thickness of the solid electrolyte interface as a function of
      time was analyzed. This paper also describes FTIR spectroscopic studies of the
      interface between lithium metal and NCPE, which suggests that the surface
      chemistry of lithium electrodes in contact with NCPE is dominated by compounds
      with C-N-Li and C-O-Li bonding.

PMID- 19161289
TI  - High-pressure effects on the electronic structure of anthracene single crystals:
      role of nonhydrostaticity.
AB  - Optical spectroscopy methods were used to examine the effect of nonhydrostaticity
      on the electronic structure of anthracene single crystals compressed statically
      to 9 GPa. Two pressure-transmitting media, nitrogen (hydrostatic) and water
      (nonhydrostatic above approximately 5.5 GPa), were utilized. It was found that
      nonhydrostatic compression generates several new features both in the absorption
      and fluorescence spectra: (i) formation of new absorption and fluorescence bands,
      (ii) deviations in pressure shift of fluorescence peaks, (iii) extensive
      broadening of vibrational peaks, and (iv) irreversible changes in the spectra
      shape upon pressure unloading. Furthermore, the time-resolved fluorescence decay
      curves measured at the wavelength corresponding to the new fluorescence band show
      clear initial increase. These new features are accompanied by inhomogeneous color
      changes and macroscopic lines on the (001) plane of the crystal. All of the
      changes are discussed and correlated with microscopic transformations in the
      crystal. It is demonstrated that nonhydrostatic compression in anthracene crystal
      introduces inelastic changes in the form of dislocations along [110] and [110]
      directions. These dislocations lead to the development of dimeric structures and,
      consequently, to various changes in the electronic response of the compressed
      anthracene crystal.

PMID- 19161290
TI  - Formation of the 1,3,5-hexatriynyl radical (C6H(X(2)Pi)) via the crossed beams
      reaction of dicarbon (C2(X(1)Sigma(g)+/a(3)Pi(u))), with diacetylene
      (C4H2(X(1)Sigma(g)+)).
AB  - Crossed molecular beams experiments were conducted to investigate the chemical
      dynamics of the reaction of dicarbon molecules, C(2)(X(1)Sigma(g)(+)/a(3)Pi(u)),
      with diacetylene, C(4)H(2)(X(1)Sigma(g)(+)) at two collision energies of 12.1 and
      32.8 kJ mol(-1). The dynamics were found to be indirect, involved C(6)H(2)
      intermediates, and were dictated by an initial addition of the dicarbon molecule
      to the carbon-carbon triple bond of diacetylene. The initial collision complexes
      could isomerize. On the singlet surface, the resulting linear triacetylene
      molecule (C(6)H(2)(X(1)Sigma(g)(+))) decomposed without an exit barrier to form
      the linear 1,3,5-hexatriynyl radical (C(6)H(X(2)Pi)). On the triplet surface, the
      dynamics suggested at least a tight exit transition state involved in the
      fragmentation of a triplet C(6)H(2) intermediate to yield the 1,3,5-hexatriynyl
      radical (C(6)H(X(2)Pi)) plus atomic hydrogen. On the basis of the experimental
      data, we recommend an experimentally determined enthalpy of formation of the
      1,3,5-hexatriynyl radical of 1014 +/- 27 kJ mol(-1) at 0 K. Our experimental
      results and the derived reaction mechanisms gain full support from electronic
      structure calculations on the singlet and triplet C(6)H(2) potential-energy
      surfaces. The identification of the 1,3,5-hexatriynyl radical under single
      collision conditions implies that the neutral-neutral reaction of dicarbon with
      diacetylene can lead to the formation of 1,3,5-hexatriynyl radicals in the
      interstellar medium and possibly in the hydrocarbon-rich atmospheres of planets
      and their moons such as Saturn's satellite Titan.

PMID- 19161291
TI  - High-temperature phase transition studies in a novel fast ion conductor,
      Na2Cd(SO4)2, probed by Raman spectroscopy.
AB  - Temperature-dependent Raman spectroscopic studies were carried out on
      Na(2)Cd(SO(4))(2) from room temperature to 600 degrees C. We observe two
      transitions at around 280 and 565 degrees C. These transitions are driven by the
      change in the SO(4) ion. On the basis of these studies, one can explain the
      changes in the conductivity data observed around 280 and 565 degrees C. At 280
      degrees C, spontaneous tilting of the SO(4) ion leads to restriction of Na(+)
      mobility. Above 565 degrees C, the SO(4) ion starts to rotate freely, leading to
      increased mobility of Na(+) ion in the channel.

PMID- 19161292
TI  - Polyisocyanides of titanium.
AB  - Neutral Ti[CN](n) complexes have been investigated with quantum chemistry
      techniques. According to our theoretical predictions, these complexes are shown
      to prefer isocyanide arrangements. Therefore, these compounds are good candidates
      to be the first polyisocyanides to be characterized. The theoretical calculations
      predict Ti(NC)(4), a methane-like tetrahedral structure with four isocyanide
      ligands, as the most stable neutral complex. The fact that the isocyanide ligand
      is a better pi-donor than the cyanide one seems to be the key factor for the
      preference for isocyanides in neutral titanium complexes.

PMID- 19161293
TI  - Aggregation models of potential cyclical trimethylsulfonium dicyanamide ionic
      liquid clusters.
AB  - Raman and infrared spectra of trimethylsulfonium dicyanamide
      [(CH(3))(3)SN(CN)(2)] are reported and accurately reproduced by DFT methods
      (B3LYP and B3PW91), MP2, and MP3, and to a lesser extent by the RHF method. The
      (CH(3))(3)SN(CN)(2) ionic liquid forms two isomeric dimers that are of cyclic
      structure, one of which is 13 kcal/mol lower in energy than the other. Both
      isomeric cyclic pairs (versions 1 and 2), [(CH(3))(3)SN(CN)(2)](2), have the
      potential to further combine and form a common structure containing four pairs of
      (CH(3))(3)SN(CN)(2). This structure can then conceivably undergo a stacking
      procedure to form extended ionic liquid nanotubes of eight ionic liquids,
      [(CH(3))(3)SN(CN)(2)](8). The possible formation of gas phase ionic liquid
      clusters of two, four, and eight trimethylsulfonium dicyanamide ionic liquids is
      supported by highly exergonic free energy changes obtained from B3LYP/(6
      311+G(d,p)) density functional calculations.

PMID- 19161294
TI  - Pyrroloquinoline quinone-doped polymeric nanospheres as sensitive tracer for
      binding assays.
AB  - The preparation and analytical characteristics of novel prosthetic group loaded
      polymeric nanospheres for use in high-sensitivity bioaffinity assays is reported.
      Pyrroloquinoline quinone (PQQ), a prosthetic group for apoglucose dehydrogenase
      (apo-GDH), is loaded into poly(methyl methacrylate) (PMMA) nanospheres in the
      presence of methanol. PQQ released from the nanospheres in the presence of 40%
      acetonitrile is capable of reconstituting apo-GDH and triggers the enzymatic
      reaction with excess glucose. The two electrons generated are transferred from a
      reduced PQQ to a redox dye reagent, e.g., 2,6-dichloroindolphenol (DCPIP). The
      decrease in absorbance of DCPIP is observed visually or spectrophotometrically to
      assess the number of particles present. As initial model systems, this concept is
      applied to develop a microtiter plate assay to detect biotin (as a model for low
      molecular weight species) and C-reactive protein (CRP). For the CRP assay,
      neutravidin-coated PQQ-doped PMMA nanospheres are used to bind with a
      biotinylated reporter antibody directed toward CRP. Detection limits to CRP at
      subnanogram per milliliter levels are demonstrated. The advantage of this type of
      assay is that excess apoenzyme can be added, with detection capability dependent
      on the number of encapsulated PQQ species that can be readily released from the
      surface-bound nanospheres (ca. 20,000 PQQ molecules/PMMA particle).

PMID- 19161295
TI  - Impact of 7,8-dihydro-8-oxoguanine on methylation of the CpG site by Dnmt3a.
AB  - 7,8-Dihydro-8-oxoguanine (8-oxoG) is a ubiquitous oxidative DNA lesion resulting
      from injury to DNA via reactive oxygen species. 8-oxoG lesions may play a role in
      the formation of aberrant DNA methylation patterns during carcinogenesis. In this
      study, we assessed the effects of 8-oxoG on methylation and complex formation of
      nine 30-mer oligodeoxynucleotide duplexes by the catalytic domain of murine
      Dnmt3a DNA methyltransferase (Dnmt3a-CD). The effects of 8-oxoG on the
      methylation rate of hemimethylated duplexes varied from a 25-fold decrease to a
      1.8-fold increase, depending on the position of the lesion relative to the Dnmt3a
      CD recognition site (CpG) and target cytosine (C). The most significant effect
      was observed when 8-oxoG replaced guanine within the recognition site immediately
      downstream of the target cytosine. Fluorescence polarization experiments with
      fluorescein-labeled duplexes revealed that two molecules of Dnmt3a-CD bind per
      duplex, generating sigmoid binding curves. Duplexes exhibiting the highest
      apparent binding cooperativity formed the least stable 1:2 complexes with Dnmt3a
      CD and were methylated at the lowest rate. Kinetic analyses disclosed the
      formation of very stable nonproductive enzyme-substrate complexes with
      hemimethylated duplexes that act as suicide substrates of Dnmt3a-CD. The presence
      of 8-oxoG within the CpG site downstream of the target cytosine markedly
      diminished productive versus nonproductive binding. We propose that 8-oxoG
      located adjacent to the target cytosine interferes with methylation by weakening
      the affinity of DNA for Dnmt3a-CD, thereby favoring a nonproductive binding mode.

PMID- 19161297
TI  - Side chains of cobalt corrinoids control the sensitivity and selectivity in the
      colorimetric detection of cyanide.
AB  - Substitution of Co(III)-bound water by cyanide allows the rapid colorimetric
      detection of micromolar amounts of cyanide with cobalt corrinoids. Negatively
      charged side chains at the periphery of these metal-based sensors increase the
      selectivity of cyanide versus thiocyanate, the most disturbing anion, by a factor
      of 30 through additional supramolecular interactions in water.

PMID- 19161296
TI  - Identification of FTIR bands due to internal water molecules around the quinone
      binding sites in the reaction center from Rhodobacter sphaeroides.
AB  - The bacterial reaction center (RC) is a membrane protein complex that performs
      photosynthetic electron transfer from a bacteriochlorophyll dimer to quinone
      acceptors Q(A) and Q(B). Q(B) accepts electrons from the primary quinone, Q(A),
      in two sequential electron transfer reactions coupled to uptake of a proton from
      solution. It has been suggested that water molecules along the proton uptake
      pathway are protonated upon quinone reduction on the basis of FTIR difference
      spectra [Breton, J., and Nabedryk, E. (1998) Photosynth. Res. 55, 301-307]. We
      examined the possible involvement of water molecules in the photoreaction
      processes by studying (18)O water isotope effects on FTIR difference spectra
      resulting from formation of Q(A)(-) and Q(B)(-). Continuum bands in D(2)O due to
      Q(B)(-) formation in the 2300-1800 cm(-1) region did not show spectral shifts by
      (18)O water in the wild-type (WT) RC, suggesting that these bands do not
      originate from (protonated) water. In contrast, the Q(B)(-)/Q(B) spectrum of the
      EQ-L212 mutant RC showed a spectral shift of a band near 2100 cm(-1) due to (18)O
      water substitution, consistent with protonation of internal water. FTIR shifts
      due to (18)O water were also observed following formation of Q(A)(-) and Q(B)(-)
      in the spectral region of 3700-3500 cm(-1) characteristic of weakly hydrogen
      bonded water. The water responsible for the Q(B)(-) change was localized near Glu
      L212 by spectral shifts in mutant RCs. The weakly hydrogen bonded water perturbed
      by quinone reduction may play a role in stabilizing the charge-separated state.

PMID- 19161298
TI  - Can in vitro metabolism-dependent covalent binding data distinguish hepatotoxic
      from nonhepatotoxic drugs? An analysis using human hepatocytes and liver S-9
      fraction.
AB  - In vitro covalent binding studies in which xenobiotics are shown to undergo
      metabolism-dependent covalent binding to macromolecules have been commonly used
      to shed light on the biochemical mechanisms of xenobiotic-induced toxicity. In
      this paper, 18 drugs (nine hepatotoxins and nine nonhepatotoxins) were tested for
      their proclivity to demonstrate metabolism-dependent covalent binding to
      macromolecules in human liver S-9 fraction (9000 g supernatant) or human
      hepatocytes, as an extension to previous work that used human liver microsomes
      published in this journal [ Obach et al. ( 2008 ) Chem. Res. Toxicol. 21 , 1814 
      1822 ]. In the S-9 fraction, seven out of the nine drugs in each category
      demonstrated some level of metabolism-dependent covalent binding. Inclusion of
      reduced glutathione, cofactors needed by conjugating enzymes, and other
      parameters (total daily dose and fraction of total intrinsic clearance comprised
      by covalent binding) improved the ability of the system to separate hepatotoxins
      from nonhepatotoxins to a limited extent. Covalent binding in human hepatocytes
      showed that six out of the nine hepatotoxins and four out of eight
      nonhepatotoxins demonstrated covalent binding. Taking into account estimates of
      total daily body burden of covalent binding from the hepatocyte data showed an
      improvement over other in vitro systems for distinguishing hepatotoxins from
      nonhepatotoxins; however, this metabolism system still displayed some false
      positives. Combined with the previous study using liver microsomes, these
      findings identify the limitations of in vitro covalent binding data for
      prospective prediction of hepatotoxicity for new drug candidates and highlight
      the need for a better understanding of the link between drug bioactivation,
      covalent adduct formation, and toxicity outcomes. Directly relating covalent
      binding to hepatotoxicity is likely an oversimplification of the process whereby
      adduct formation ultimately leads to toxicity. Understanding underlying
      complexities (e.g., which macromolecules are important covalent binding targets,
      interindividual differences in susceptibility, etc.) will be essential to any
      understanding of the problem of metabolism-dependent hepatotoxicity and
      predicting toxicity from in vitro experiments.

PMID- 19161299
TI  - Scattering orthogonalization of near-infrared spectra for analysis of
      pharmaceutical tablets.
AB  - The paper explores scattering orthogonalization as a preprocessing technique to
      reduce physical interference and maintain chemical information in near-infrared
      (NIR) spectra of pharmaceutical tablets. Samples used in this study were tablets
      compressed at five compression forces; they were composed of theophylline,
      lactose, and microcrystalline cellulose (PH200). The NIR spectra were
      orthogonalized against the reduced scattering coefficients (representative of
      physical interference of scattering), and concentrations of all constituents were
      predicted. The robustness of predictions was compared to the widely employed
      standard normal variate (SNV) for the specificity of removing interference
      representative of physical parameter (such as tablet density). Group-wise cross
      validation (groups were based upon similar chemical composition) and prediction
      demonstrated the enhanced robustness on prediction of chemical information via
      scattering orthogonalization in comparison to SNV. When compared to the SNV,
      scattering orthogonalization demonstrated an improved capacity to reduce physical
      interference while maintaining spectral variance attributable to chemical
      information. The improved capacity is expected to be useful for spectroscopy
      based multivariate model calibration and continuous model update.

PMID- 19161300
TI  - Analysis of biological fluids by direct combination of solid phase extraction and
      desorption electrospray ionization mass spectrometry.
AB  - A novel, solid phase extraction (SPE)-based sample preparation method was
      developed for desorption electrospray ionization (DESI) mass spectrometry.
      Conventional SPE sample preparation was followed by a custom elution procedure.
      The eluate was evaporated from the closing frit of the cartridge using a gas jet.
      Thus the analyte was concentrated on the surface of the frit, which is ideal for
      DESI analysis. Application of the above SPE protocol allowed the concentration of
      the analyte content of up to 1 L liquid sample into a 1 mm diameter circular
      spot. The sample preparation procedure can improve the overall sensitivity of the
      method by up to 6 orders of magnitude if the sample volume is sufficient. The
      device has been tested using aqueous solutions of Rhodamine 116; the limit of
      detection was comparable to the LOD of electrospray analysis. Methodology was
      tested for drug monitoring applications in human serum. Levels of Cyclosporine A
      were determined using a 0.1 mL serum sample. Dynamic range of the method exceeded
      3 orders of magnitude; the detection limit was below the therapeutic serum
      concentration of the drug.

PMID- 19161301
TI  - Synthesis of epoxides by palladium-catalyzed reactions of tertiary allyl alcohols
      with aryl or alkenyl halides.
AB  - A novel synthetic method for the preparation of tri- or tetrasubstituted epoxides
      is reported. Treatment of readily available tertiary allyl alcohol with aryl or
      alkenyl halide under palladium catalysis resulted in arylative cyclization to
      form the epoxide. The reaction includes intramolecular C-O bond and
      intermolecular C-C bond construction.

PMID- 19161302
TI  - Nazarov type cyclization on an osmium-dienylcarbene complex.
AB  - The Nazarov reaction is an acid-catalyzed 4pi-electrocyclic ring closure of
      dienylketones, which affords cyclopentenones. This type of cyclization has been
      increasing in interest over the years, due to the importance of the construction
      of five-membered rings in the synthesis of natural products. However, one
      potential problem is that the carbonyl group necessary for the cyclization to
      occur may not be required in the final synthetic target and can sometimes be
      difficult to remove or modify. One possible solution is to design analogous
      reactions which do not suffer the carbonyl dependence.

PMID- 19161303
TI  - Evaluation of a microfluidic device for the electrochemical determination of
      halide content in ionic liquids.
AB  - A microfluidic device designed for electrochemical studies on a microliter scale
      has been utilized for the examination of impurity levels in ionic liquids (ILs).
      Halide impurities are common following IL synthesis, and this study demonstrates
      the ability to quantify low concentrations of halide in a range of ILs to levels
      of approximately 5 ppm, even in ILs not currently measurable using other methods
      such as ion chromatography. To validate the mixer device, the electrochemistry of
      ferrocene was also examined and compared with spectroscopic and bulk
      electrochemistry measurements. An automated "sample preparation, delivery, and
      calibration" method was developed, and the chip successfully used for linear
      sweep, cyclic voltammetry (under both quiescent and steady-state flowing
      conditions), square wave voltammetry, and differential pulse voltammetry. An
      effective method of electrochemically cleaning the electrodes is also presented.

PMID- 19161305
TI  - Oxy-functionalization of nucleophilic rhenium(I) metal carbon bonds catalyzed by
      selenium(IV).
AB  - We report that SeO2 catalyzes the facile oxy-functionalization of (CO)5Re(I)
      Me(delta-) with IO4(-) to generate methanol. Mechanistic studies and DFT
      calculations reveal that catalysis involves methyl group transfer from Re to the
      electrophilic Se center followed by oxidation and subsequent reductive
      functionalization of the resulting CH3Se(VI) species. Furthermore,
      (CO)3Re(I)(Bpy)-R (R = ethyl, n-propyl, and aryl) complexes show analogous
      transfer to SeO2 to generate the primary alcohols. This represents a new strategy
      for the oxy-functionalization of M-R(delta-) polarized bonds.

PMID- 19161304
TI  - Ru(bpy)(3) covalently doped silica nanoparticles as multicenter tunable
      structures for electrochemiluminescence amplification.
AB  - The electrochemiluminescence (ECL) of doped silica nanoparticles (DSNPs),
      prepared by a reverse microemulsion method that leads to covalent incorporation
      of the Ru(bpy)(3)(2+), was investigated in acetonitrile and aqueous buffers. The
      emission was produced for the first time by cation-anion direct annihilation, and
      the position of ECL maxima indirectly allowed estimation of the E(1/2,IOx) and
      E(1/2,IRed) potentials for Ru(bpy)(3) inside DSNPs. The weak ECL emission is most
      likely generated by an intrananoparticle ruthenium unit annihilation rather than
      by the electron transfer between a reduced and oxidized DSNP due to the very low
      diffusivities of the nanoparticles. Thiol-terminated DSNPs were self-assembled on
      gold substrates, forming compact and stable monolayers which mimic probe-target
      assays with DSNPs as labels. The ECL intensity obtained by such functionalized
      substrates in aqueous media, using tripropylamine (TPrA) as coreactant, was
      surprisingly increased with respect to direct electrochemical oxidation because
      of the ability of oxidized TPrA to diffuse within the DSNPs structure and reach a
      higher number of emitting units with respect to direct electron tunneling. The
      experimental results have been explained by proposing a basic physical-chemical
      model which supports evaluation of the number of redox-active centers per
      nanoparticle. In the model the contrasting effects of increased luminescence
      quantum yield and decreased diffusion coefficient with respect to free (i.e., not
      bound within the silica structure) emitting molecules were taken into account.
      This allows, in principle, optimizing the ECL emission intensity as a function of
      DSNP size, doping material, charge, doping level, supporting electrolyte,
      electrode material, and solvent. Finally, it is worth noting that this study has
      provided a more than 1000-fold increase of the ECL signal of a chemically and
      electrochemically stable DSNP compared to that of a single dye, suggesting that
      use of this kind of nanostructures as luminescent labels represents a very
      promising system for ultrasensitive bioanalysis.

PMID- 19161307
TI  - Mixed-valent {Mn14} aggregate encapsulated by the inorganic polyoxometalate
      shell: [Mn(III)13Mn(II)O12(PO4)4(PW9O34)4]31-.
AB  - The reaction of [Mn(12)(CH(3)COO)(16)(H(2)O)(4)O(12)].2CH(3)COOH.4H(2)O,
      Na(8)[HPW(9)O(34)].24H(2)O, K(2)HPO(4), and ethylenediamine hydrochloride in an
      aqueous solution leads to the isolation of a new polyoxometalate-based mixed
      valent manganese aggregate,
      K(14)Na(17)[(Mn(III)(13)Mn(II)O(12)(PO(4))(4)(PW(9)O(34))(4)]. approximately
      56H(2)O (1). Single-crystal X-ray diffraction indicates that the polyoxoanion of
      1 exhibits a mixed-valent [Mn(III)(13)Mn(II)(mu(2)-O)(6)(mu(3)-O)(6)(mu(4)
      PO(4))(2)(mu(5)-PO(4))(2)](5+) complex encapsulated by four [B-alpha
      PW(9)O(34)](9-) trivacant Keggin-type moieties [crystal data for 1: monoclinic,
      C2/c (No. 15), a = 36.341(7) A, b = 18.325(4) A, c = 36.668(7) A, beta =
      119.24(3) degrees, V = 21308(7) A(3), Z = 4]. In a magnetic point of view, all of
      these paramagnetic manganese aggregates in 1 are well wrapped into the
      diamagnetic inorganic shells. Variable-temperature, solid-state, direct-current
      susceptibility measurements show that compound 1 exhibits strong
      antiferromagnetic interactions inside the [Mn(14)] core.

PMID- 19161306
TI  - Asymmetric synthesis of medium-sized rings by intramolecular Au(I)-catalyzed
      cyclopropanation.
AB  - An efficient method for the asymmetric gold(I)-catalyzed preparation of medium
      sized rings has been developed. The method provides 7- to 9-membered rings in
      excellent yield. High enantioselectivities can be achieved for 7- and 8-membered
      ring products employing chiral gold(I) complexes. The results provide insight
      into the mechanism, showing the fluxional nature of gold(I)-stabilized vinyl
      carbenoid intermediates.

PMID- 19161309
TI  - Mononuclear ferrocenophane structural motifs with two thiourea arms acting as a
      dual binding site for anions and cations.
AB  - The synthesis of a new type of mononuclear ferrocenophane-based thiourea, in
      which the ferrocene moiety is simultaneously attached to two thiourea groups
      directly from 1,1'-bis(isothiocyanato)ferrocene, is reported. These nitrogen-rich
      structural motifs show remarkable ion-sensing properties because of the presence
      of the redox active ferrocene unit and the thiourea bridges, which unexpectedly
      act as a dual binding site for anions and metal ions. They display a selective
      downfield shift of the thiourea protons and a remarkable cathodic shift of the
      ferrocene/ferrocenium redox couple with F(-), AcO(-), H(2)PO(4)(-), and
      HP(2)O(7)(3-) anions, whereas the selective recognition of Hg(2+) metal cations
      is achieved either by electrochemical or by spectral measurements. The preferred
      binding modes are proposed for the most representative complexes by means of
      density functional theory based theoretical calculations showing the Janus-like
      faces of the receptor.

PMID- 19161308
TI  - Total synthesis of photoactivatable or fluorescent anandamide probes: novel
      bioactive compounds with angiogenic activity.
AB  - Endocannabinoids are endogenous polyunsaturated fatty acids involved in a
      multitude of health and disease processes. Recently, several lines of evidence
      suggest the presence of a novel non-CB1/CB2 anandamide receptor in endothelial
      cells. Thus, we synthesized two types of photoaffinity probes that contain either
      an arylazide group or a diazirin moiety, together with a fluorescent analogue.
      The key steps rely on selective hydrogenation of skipped tetrayne backbones and
      on copper-mediated cross-coupling reactions between diynic precursors. Three
      synthetic routes were investigated. In biological functional assays, we found
      that both the arylazide and the fluorescent probes induced robust increases in
      matrix metalloprotease activity and produced positive angiogenic responses in in
      vitro endothelial cell tube formation assays. Irradiation of the arylazide probe
      nicely enhanced this effect in both HUVEC and CB1-KO HUVEC. These results suggest
      that the arylazide and the fluorescent probes can be used to identify "non
      CB1/CB2 anandamide receptor" from endothelial cells.

PMID- 19161310
TI  - Supercoil-accelerated DNA threading intercalation.
AB  - The effect of DNA supercoiling on a sterically very demanding threading
      intercalation process is investigated here. We find that the threading rate of a
      dimeric ruthenium complex into a negatively supercoiled plasmid at low binding
      density is 2 orders of magnitude higher than into the cleaved linear form.
      Further saturation is on the other hand kinetically hampered in comparison to the
      relaxed DNA. We also observe that threading kinetics correlates with the
      inhibition of luciferase expression from the plasmid construct. The results show
      how the target torsional strain can function as a control of DNA threading
      kinetics and gene expression efficiency.

PMID- 19161311
TI  - Effects of mainstream cigarette smoke on the global metabolome of human lung
      epithelial cells.
AB  - Metabolomics is a technology for identifying and quantifying numerous
      biochemicals across metabolic pathways. Using this approach, we explored changes
      in biochemical profiles of human alveolar epithelial carcinoma (A549) cells
      following in vitro exposure to mainstream whole smoke (WS) aerosol as well as to
      wet total particulate matter (WTPM) or gas/vapor phase (GVP), the two constituent
      phases of WS from 2R4F Kentucky reference cigarettes. A549 cells were exposed to
      WTPM or GVP (expressed as WTPM mass equivalent GVP volumes) at 0, 5, 25, or 50
      microg/mL or to WS from zero, two, four, and six cigarettes for 1 or 24 h. Cell
      pellets were analyzed for perturbations in biochemical profiles, with named
      biochemicals measured, analyzed, and reported in a heat map format, along with
      biochemical and physiological interpretations (mSelect, Metabolon Inc.). Both
      WTPM and GVP exposures likely decreased glycolysis (based on decreased glycolytic
      intermediaries) and increased oxidative stress and cell damage. Alterations in
      the Krebs cycle and the urea cycle were unique to WTPM exposure, while induction
      of hexosamines and alterations in lipid metabolism were unique to GVP exposure.
      WS altered glutathione (GSH) levels, enhanced polyamine and pantothenate levels,
      likely increased beta-oxidation of fatty acids, and increased phospholipid
      degradation marked by an increase in phosphoethanolamine. GSH, glutamine, and
      pantothenate showed the most significant changes with cigarette smoke exposure in
      A549 cells based on principal component analysis. Many of the changed
      biochemicals were previously reported to be altered by cigarette exposure, but
      the global metabolomic approach offers the advantage of observing changes to
      hundreds of biochemicals in a single experiment and the possibility for new
      discoveries. The metabolomic approach may thus be used as a screening tool to
      evaluate conventional and novel tobacco products offering the potential to reduce
      risks of smoking.

PMID- 19161312
TI  - Application of the stabilization method to the pi* temporary anion states of
      benzene and substituted benzenes in density functional theory.
AB  - The stabilization method is used in conjunction with Koopmans-based approximation
      to calculate the energies of pi* temporary anion states of a series of
      substituted benzenes in density functional theory. In this approach, the Koopmans
      expression is corrected due to the consideration of the integer discontinuities
      in the exact exchange-correlation potential. Stabilization is accomplished by
      varying the exponents of appropriate diffuse functions. The energies of pi*
      states are then identified by investigating the relationship between the
      resultant eigenvalues and scale parameter. Results indicate that this approach
      can yield an improvement in the predictions of the absolute energies of pi*
      states over other methods.

PMID- 19161313
TI  - Theoretical calculation of separation factors for boron isotopic exchange between
      BF3 and BF3 x C6H5OCH3.
AB  - The separation factors (or equilibrium constants) for boron isotopic exchange
      reaction (10)BF(3) + (11)BF(3) x C(6)H(5)OCH(3) <==> (11)BF(3) + (10)BF(3) x
      C(6)H(5)OCH(3) were obtained from MP2/6-31+G(d,p) and B3LYP/6-31+G(d,p)
      calculations. New scaling factors, single and multiple, were derived from the
      harmonic frequencies through the least-squares fit for BF(3) and C(6)H(5)OCH(3).
      The use of multiple scaling factors in the case of C(6)H(5)OCH(3) led to
      significant improvement in the calculated frequencies over using a single scaling
      factor. There exists a negligible difference in the separation factors obtained
      by using the harmonic and the scaled frequencies of the same method, and in those
      obtained by using different methods. The calculated separation factors for the
      boron isotopic exchange reaction at 273.15, 293.15, and 298.15K are 1.039, 1.036,
      and 1.035, respectively, which are in excellent agreement with the experimental
      values, 1.041 +/- 0.002, 1.030 +/- 0.002, and 1.035 +/- 0.003. This study
      demonstrated the promise of using DFT (B3LYP) to obtain separation factors for
      the reactions where the interactions are weaker than covalent bonds but stronger
      than van der Waals interactions, and consequently to search for better
      complexation agents than C(6)H(5)OCH(3) for the isotopic separation of BF(3).

PMID- 19161314
TI  - Synthesis and characterization of all four diastereomers of 3,4-dichloro-2
      pentanol, motifs relevant to the chlorosulfolipids.
AB  - All four diastereomers of 3,4-dichloro-2-pentanol were synthesized by anti
      dichlorination of the precursor allylic alcohols; their stereochemistry was
      elucidated by X-ray crystallographic analysis of tosylate derivatives. Complete
      NMR data is provided in the hope that this information will facilitate structural
      elucidation and synthesis studies on the chlorosulfolipid family of natural
      products, such as malhamensilipin A.

PMID- 19161315
TI  - Theoretical study of the catalysis of cyanohydrin formation by the cyclic
      dipeptide catalyst cyclo[(S)-His-(S)-Phe].
AB  - Dipeptide cyclo[(S)-His-(S)-Phe] 1, first applied by Inoue et al. in 1981,
      catalyzes the hydrocyanation of aromatic aldehydes very efficiently.
      Enantioselective autoinduction has also been reported for the process. We have
      employed QM (density functional theory and MP2), molecular mechanics (MM), and
      molecular dynamics (MD) methods to (i) derive a mechanistic picture for catalysis
      and (ii) reveal the origin of stereochemistry and autoinduction. A dimer is
      proposed to be the catalytic species, in which one imidazole group is essential
      for the delivery of the nucleophile and the second imidazole group acts as an
      acid, accompanied with pi-interaction for most favorable substrate binding.
      Hydrogen-bonding via hydroxy groups is crucial for catalysis also. MD studies
      indicate stability of the dimer only in non-polar media, which is consistent with
      the need of the experimental (heterogeneous) reaction conditions to achieve high
      enantioselectivities. DFT and MP2 results suggest the incorporation of the
      product cyanohydrin via extended edge-to-face pi-interaction over three aromatic
      units. Transition states derived from this model are in good agreement with
      experimental findings and enantioselectivities.

PMID- 19161317
TI  - Intermolecular antiselective and enantioselective reductive coupling of enones
      and aromatic aldehydes with chiral Rh(Phebox) catalysts.
AB  - The intermolecular reductive coupling reaction of cyclopent-2-enone and aromatic
      aldehydes was realized by chiral rhodium-(bisoxazolinyl)phenyl catalysts,
      Rh(Phebox-Ph)(OAc)(2)(H(2)O), with diphenymethylsilane as a hydride donor to give
      the corresponding beta-hydroxyketones in high anti-selectivity (up to 96%) with
      high enantioselectivity (up to 93%).

PMID- 19161316
TI  - Use of the in vivo hollow fiber assay in natural products anticancer drug
      discovery.
AB  - The in vivo hollow fiber assay was developed at the National Cancer Institute
      (NCI) to help bridge the gap between in vitro cell-based assays and human tumor
      models propagated in immunodeficient mice. The goal was to develop an
      intermediate assay that could help predict which compounds found active in the 60
      cell line panel would be active in a subsequent xenograft system. This was
      necessary due to the high cost of the traditional xenograft assay in terms of
      number of animals required, time for assay completion, and financial commitment
      necessary. To address this problem, investigators of the NCI Developmental
      Therapeutics Program designed a method of propagating human cancer cells in inert
      hollow fibers with pores small enough to retain the cancer cells but large enough
      to permit entry of potential chemotherapeutic drugs, including large proteins and
      other important substances. Fibers containing proliferating cancer cells are
      transplanted into the peritoneum or under the skin, the host mice are treated
      with a test agent, and the fibers are subsequently retrieved for analysis of
      viable cell mass. The assay has been successful in helping investigators from
      around the world, including our own research group, prioritize compounds active
      in vitro for further testing in the traditional xenograft system.

PMID- 19161318
TI  - A Dimeric sesquiterpenoid from a Malaysian Meiogyne as a new inhibitor of Bcl
      xL/BakBH3 domain peptide interaction.
AB  - In an effort to find potent inhibitors of the antiapoptotic protein Bcl-xL, a
      systematic in vitro evaluation was undertaken on 1470 Malaysian plant extracts.
      The ethyl acetate extract obtained from the bark of Meiogyne cylindrocarpa was
      selected for its interaction with the Bcl-xL/Bak association. Bioassay-guided
      purification of this species led to the isolation of two new dimeric
      sesquiterpenoids (1 and 2) possessing an unprecedented substituted cis-decalin
      carbon skeleton. Meiogynin A (1) showed the strongest activity with a K(i) of
      10.8 +/- 3.1 microM.

PMID- 19161319
TI  - Catalytic redox-initiated glycolate aldol additions of silyl glyoxylates.
AB  - Lanthanide triisopropoxides catalyze a rapid, tandem MPV reduction/Brook
      rearrangement/aldol sequence between silyl glyoxylates and aldehydes that
      achieves catalytic turnover through alkoxide transfer from a strain-release Lewis
      acidic silacycle.

PMID- 19161320
TI  - A versatile approach to beta-amyloid fibril-binding compounds exploiting the
      Shirakawa/Hayashi protocol for trans-alkene synthesis.
AB  - Application of the Sonogashira coupling reaction followed by a trans-selective
      alkyne reduction proved highly adaptable for the efficient synthesis of a class
      of beta-amyloid fibril binding compounds possessing a styrylbenzene motif such as
      FSB, an FSB dimer, and (19)F-BAY94-9172.

PMID- 19161321
TI  - Unexpected orthogonality of S-benzoxazolyl and S-thiazolinyl glycosides:
      application to expeditious oligosaccharide assembly.
AB  - Thorough mechanistic studies of the alkylation pathway for the activation of
      glycosyl thioimidates have led to the development of the "thioimidate-only
      orthogonal strategy". Discrimination among S-thiazolinyl (STaz) and S
      benzoxazolyl (SBox) anomeric leaving groups was achieved by fine-tuning of the
      activation conditions. Preferential glycosidation of a certain thioimidate is not
      simply determined by the strength of activating reagents; instead, the type of
      activation--direct vs indirect--comes to the fore and plays the key role.

PMID- 19161322
TI  - Direct observation of Born-Oppenheimer approximation breakdown in carbon
      nanotubes.
AB  - Raman spectra and electrical conductance of individual, pristine, suspended,
      metallic single-walled carbon nanotubes are measured under applied gate
      potentials. The G(-) band is observed to downshift with small applied gate
      voltages, with the minima occurring at E(F) = +/-(1)/(2)E(phonon), contrary to
      adiabatic predictions. A subsequent upshift in the Raman frequency at higher gate
      voltages results in a "W"-shaped Raman shift profile that agrees well with a
      nonadiabatic phonon renormalization model. This behavior constitutes the first
      experimental confirmation of the theoretically predicted breakdown of the Born
      Oppenheimer approximation in individual single-walled carbon nanotubes.

PMID- 19161323
TI  - Layer-by-layer technique as a new approach to produce nanostructured films
      containing phospholipids as transducers in sensing applications.
AB  - Phospholipids are widely used as mimetic systems to exploit interactions
      involving biological membranes and pharmacological drugs. In this work, the layer
      by-layer (LbL) technique was used as a new approach to produce multilayered thin
      films containing biological phospholipids applied as transducers onto Pt
      interdigitated electrodes forming sensing units of an electronic tongue system.
      Low concentrations (nM level) of a phenothiazine compound were detected through
      impedance spectroscopy. Both negative 1,2-dipalmitoyl-sn-3-glycero-[phosphor-rac
      (1-glycerol)] (DPPG) and zwitterionic l-alpha-1,2-dipalmitoyl-sn-3-glycero
      phosphatidylcholine (DPPC) phospholipids were used to produce the LbL films,
      whose molecular architecture was monitored combining spectroscopy and microscopy
      at micro and nanoscales. The sensor array was complemented by Langmuir-Blodgett
      (LB) monolayers of DPPG and DPPC deposited onto Pt interdigitated electrodes as
      well. It was found that the distinct molecular architecture presented by both LbL
      and LB films plays a key role on the sensitivity of the sensor array with the
      importance of the LbL films being demonstrated by principal component analysis
      (PCA).

PMID- 19161324
TI  - Asymmetric synthesis of both antipodes of beta-hydroxy nitriles and beta-hydroxy
      carboxylic acids via enzymatic reduction or sequential reduction/hydrolysis.
AB  - Use of isolated carbonyl reductases in the reduction of aromatic beta
      ketonitriles have completely eliminated the competing alpha-ethylation, which is
      often observed with whole cell biocatalysts. By choosing suitable recombinant
      carbonyl reductase, the reduction of beta-ketonitriles afforded (R)- or (S)-beta
      hydroxy nitriles with excellent optical purity and yield. Subsequently, nitrilase
      catalyzed hydrolysis of the obtained optically pure beta-hydroxy nitriles led to
      the corresponding beta-hydroxy carboxylic acids in high yields. More importantly,
      the sequential enzymatic reduction and hydrolysis could be carried out in "two
      step-one-pot" fashion without the isolation of intermediates beta-hydroxy
      nitriles, lowering the cost and minimizing the environmental impact. This allows
      ready access to both antipodes of chiral beta-hydroxy nitriles and beta-hydroxy
      carboxylic acids of pharmaceutical importance with excellent optical purity.

PMID- 19161325
TI  - Ionic liquid tunes microemulsion curvature.
AB  - Middle-phase microemulsions formed from cationic dioctadecyldimethylammonium
      chloride (DODMAC), anionic sodium dodecylsulfate (SDS), n-butanol, and n-heptane
      were studied. An ionic liquid (IL), 1-butyl-3-methylimidazolium tetrafluoroborate
      ([bmim][BF4]), was employed as the electrolyte in the aqueous media instead of
      inorganic salts usually used in microemulsion formulation. Studies have been
      carried out as a function of the concentrations of [bmim][BF4], n-butanol, total
      surfactant (cDODMAC+SDS), and temperature on the phase behavior and the ultralow
      interfacial tensions in which the anionic component is present in excess in the
      catanionic film. Ultralow interfacial tension measurements confirmed the
      formation of middle-phase microemulsions and the necessary conditions for
      stabilizing middle-phase microemulsions. Electrical conductivity, small-angle X
      ray scattering (SAXS), and small-angle neutron scattering (SANS) experiments were
      also performed, indicating that the typical heptane domain size has an average
      radius of 360 A and the ionic liquid induces softening of the charged catanionic
      film. Most interestingly, the IL concentration (cIL) is shown to act as an
      effective interfacial curvature-control parameter, representing a new approach to
      tuning the formulation of microemulsions and emulsions. The results expand the
      potential uses of ILs but also point to the design of new ILs that may achieve
      superefficient control over interfacial and self-assembly systems.

PMID- 19161326
TI  - Proteomic expression signature distinguishes cancerous and nonmalignant tissues
      in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is an aggressive liver cancer but clinically
      validated biomarkers that can predict natural history of malignant progression
      are lacking. The present study explored the proteome-wide patterns of HCC to
      identify biomarker signature that could distinguish cancerous and nonmalignant
      liver tissues. A retrospective cohort of 80 HBV-associated HCC was included and
      both the tumor and adjacent nontumor tissues were subjected to proteome-wide
      expression profiling by 2-DE method. The subjects were randomly divided into the
      training (n = 55) and validation (n = 25) subsets, and the data analyzed by
      classification-and-regression tree algorithm. Protein markers were characterized
      by MALDI-ToF/MS and confirmed by immunohistochemistry, Western blotting and qPCR
      assays. Proteomic expression signature composed of six biomarkers (haptoglobin,
      cytochrome b5, progesterone receptor membrane component 1, heat shock 27 kDa
      protein 1, lysosomal proteinase cathepsin B, keratin I) was developed as a
      classifier model for predicting HCC. We further evaluated the model using both
      leave-one-out procedure and independent validation, and the overall sensitivity
      and specificity for HCC both are 92.5%, respectively. Clinical correlation
      analysis revealed that these biomarkers were significantly associated with serum
      AFP, total protein levels and the Ishak's score. The described model using
      biomarker signatures could accurately distinguish HCC from nonmalignant tissues,
      which may also provide hints on how normal hepatocytes are transformed to
      malignant state during tumor progression.

PMID- 19161327
TI  - Toward accurate screening in computer-aided enzyme design.
AB  - The ability to design effective enzymes is one of the most fundamental challenges
      in biotechnology and in some respects in biochemistry. In fact, such ability
      would be one of the most convincing manifestations of a full understanding of the
      origin of enzyme catalysis. In this work, we explore the reliability of different
      simulation approaches, in terms of their ability to rank different possible
      active site constructs. This validation is done by comparing the ability of
      different approaches to evaluate the catalytic contributions of various residues
      in chorismate mutase. It is demonstrated that the empirical valence bond (EVB)
      model can serve as a practical yet accurate tool in the final stages of computer
      aided enzyme design (CAED). Other approaches for fast screening are also examined
      and found to be less accurate and mainly useful for qualitative screening of
      ionized residues. It is pointed out that accurate ranking of different options
      for enzyme design cannot be accomplished by approaches that cannot capture the
      electrostatic preorganization effect. This is in particular true with regard to
      current design approaches that use gas phase or small cluster calculations and
      then estimate the interaction between the enzyme and the transition state (TS)
      model rather than the TS binding free energy or the relevant activation free
      energy. The ability of the EVB model to provide a tool for quantitative ranking
      in the final stage of CAED may help in progressing toward the design of enzymes
      whose catalytic power is closer to that of native enzymes than to that of the
      current generation of designer enzymes.

PMID- 19161328
TI  - Mapping NO movements in crystalline [Fe(Porph)(NO)(1-MeIm)].
AB  - Orientational disorder of the distal nitrosyl (NO) ligand in iron porphyrinates
      is a common phenomenon. We present an analysis of multitemperature
      crystallographic data for the order/disorder phenomenon. The observed temperature
      dependent order/disorder and variable rotational orientations of nitrosyl ligands
      for six different six-coordinate iron porphyrinates have been examined in terms
      of the nonbonded contacts found in the solid state. Favorable orientations for NO
      can be identified either by calculation of the close nonbonded contacts or by
      evaluation of the geometry-dependent potential energy using semiempirical
      nonbonded potential functions. The nonbonded contacts display temperature
      dependent differences consistent with observed structural differences. The motion
      of NO appears to be controlled by intermolecular interactions that allow a
      limited set of orientations, and under some conditions, only a single NO
      orientation is allowed. In some cases, the equilibria involving the orientations
      of NO can be analyzed using the van't Hoff relationship, and the free energy and
      enthalpy of the solid-state transitions can be evaluated. The intrinsic barriers
      to rotation of the NO were examined using a fine-meshed series of DFT
      calculations. The calculations also showed the detailed effects of the variation
      of the NO orientation on the equatorial bond distances.

PMID- 19161329
TI  - Redox site-mediated charge transport in a Hg-SAM//Ru(NH(3))(6)(3+/2+)//SAM-Hg
      junction with a dynamic interelectrode separation: compatibility with redox
      cycling and electron hopping mechanisms.
AB  - This paper describes the formation and electrical properties of a new Hg-based
      metal-molecules-metal junction that incorporates charged redox sites into the
      space between the electrodes. The junction is formed by bringing into contact two
      mercury-drop electrodes whose surfaces are covered by COO(-)-terminated self
      assembled monolayers (SAMs) and immersed in a basic aqueous solution of
      Ru(NH(3))(6)Cl(3). The electrical behavior of the junction, which is contacted at
      its edges by aqueous electrolyte solution, has been characterized
      electrochemically. This characterization shows that current flowing through the
      junction on the initial potential cycles is dominated by a redox-cycling
      mechanism and that the rates of electron transport can be controlled by
      controlling the potentials of the mercury electrodes with respect to the redox
      potential of the Ru(NH(3))(6)(3+/2+) couple. On repeated cycling of the potential
      across the junction, the current across it increases by as much as a factor of
      40, and this increase is accompanied by a large (>300 mV) negative shift in the
      formal potential for the reduction of Ru(NH(3))(6)(3+). The most plausible
      rationalization of this behavior postulates a decrease in the size of the gap
      between the electrodes with cycling and a mechanism of conduction dominated by
      physical diffusion of Ru(NH(3))(6)(3+/2+) ions (at larger interelectrode
      spacing), with a possible contribution of electron hopping to charge transport
      (at smaller interelectrode spacing). In this rationalization, the negative shift
      in the formal potential plausibly reflects extrusion of the solution of
      electrolyte from the junction and an increase in the effective concentration of
      negatively charged species (surface-immobilized COO(-) groups) in the volume
      bounded by the electrodes. This junction has the characteristics required for use
      in screening and in exploratory work, involving nanogap electrochemical systems,
      and in mechanistic studies involving these systems. It does not have the
      stability needed for long-term technological applications.

PMID- 19161330
TI  - Site-specific fabrication of Fe particles for carbon nanotube growth.
AB  - We report a method for site-specific fabrication of Fe catalyst particles on
      silica (SiO(2)) substrate by electron beam induced decompositionat 650 (EBID) of
      iron nonacarbonyl. The unobstructed, atomic level in situ observations of the
      catalyst particles, recorded degrees C in 8-15 mTorr of acetylene, reveal the
      structural transformations during reduction, sintering, carburization of Fe
      nanoparticles and subsequent CNT growth.

PMID- 19161331
TI  - Development of an arylthiobismuthine cocatalyst in organobismuthine-mediated
      living radical polymerization: applications for synthesis of ultrahigh molecular
      weight polystyrenes and polyacrylates.
AB  - Diphenyl(2,6-dimesitylphenylthio)bismuthine (1a) serves as an excellent
      cocatalyst in organobismuthine-mediated living radical polymerization (BIRP).
      Both low and high molecular weight polystyrenes and poly(butyl acrylate)s (PBAs)
      with controlled molecular weights and low polydispersity indexes (PDIs) were
      synthesized by the addition of a catalytic amount of 1a to an organobismuthine
      chain-transfer agent, methyl 2-dimethylbismuthanyl-2-methylpropionate (3). The
      number-average molecular weight (M(n)) of the resulting polymers increases
      linearly with the monomer/3 ratio. Structurally well-defined polystyrenes with
      M(n)'s in the range from 1.0 x 10(4) to 2.0 x 10(5) and PDIs of 1.07-1.15 as well
      as PBAs with M(n)'s in the range from 1.2 x 10(4) to 2.8 x 10(6) and PDIs of 1.06
      1.43 were successfully prepared under mild thermal conditions. Control
      experiments suggested that 1a reversibly reacts with the polymer-end radical to
      generate an organobismuthine dormant species and 2,6-dimesitylphenylthiyl radical
      (2a). This reaction avoids the occurrence of chain termination reactions
      involving the polymer-end radicals and avoids undesired loss of the bismuthanyl
      polymer end group. The bulky 2,6-dimesitylphenyl group attached to the sulfur
      atom may prevent the addition of thiyl radicals to the vinyl monomers to generate
      new polymer chains.

PMID- 19161332
TI  - Development of a multilane channel system for nongel-based two-dimensional
      protein separations using isoelectric focusing and asymmetrical flow field-flow
      fractionation.
AB  - A dual purpose multilane channel system to carry out isoelectric focusing (IEF)
      and asymmetrical flow field-flow fractionation (IEF-AFlFFF or IEF-AF4) was
      developed for the high-speed fractionation of a proteome in two dimensions (2D):
      isoelectric point (pI) and hydrodynamic diameter (d(s)). Separation of proteins
      is initially achieved by differences in pI using IEF in an open thin segment,
      which is formed by interconnecting the beginning part of six parallel flow FFF
      channels in the lateral direction. After IEF, each protein pool of a different pI
      interval is simultaneously separated in an orthogonal direction by d(s) in six
      individual AF4 channels. The developed IEF-AF4 multilane channel system provides
      ultimate nongel, elution based, and 2D protein separation at an improved
      separation speed; the entire separation can be processed within 30 min, compared
      to approximately 3 h with the previously developed capillary isoelectric focusing
      hollow fiber FlFFF (CIEF-HFFlFFF or CIEF-HF5) (Kang, D.; Moon, M. H. Anal. Chem.
      2006, 78, 5789-5798) or approximately 36 h with 2D-polyacryamide gel
      electrophoresis (2D-PAGE). An initial evaluation of IEF-AF4 was performed to
      investigate the influence of ampholyte concentration and IEF voltage on the
      separation of standard protein mixtures.

PMID- 19161333
TI  - Fabrication and field emission properties of triode-type carbon nanotube emitter
      arrays.
AB  - We report here an effective method for the fabrication of a large number of
      triode-type microgated carbon nanotube field emitter arrays. Our technique
      combines dual-beam focused ion beam technology and plasma-enhanced chemical vapor
      deposition, avoiding the tedious lithography and wet chemistry procedures
      conventionally used to fabricate such structures. Field emission testing revealed
      that increasing gate voltage by as little as 0.3 V had significant impact on the
      local electric fields, lowering the turn on and threshold fields by 3.6 and 3.0
      V/microm, respectively. The field enhancement factor of the emitter arrays was
      also increased from 149 to 222. A quantum mechanical model for such triode-type
      field emission indicates that the local electric field generated by a negatively
      or positively biased gate directly impacts the tunneling barrier thickness and
      thus the achievable emitter current.

PMID- 19161334
TI  - Wafer-scale, sub-5 nm junction formation by monolayer doping and conventional
      spike annealing.
AB  - We report the formation of sub-5 nm ultrashallow junctions in 4 in. Si wafers
      enabled by the molecular monolayer doping of phosphorus and boron atoms and the
      use of conventional spike annealing. The junctions are characterized by secondary
      ion mass spectrometry and noncontact sheet resistance measurements. It is found
      that the majority ( approximately 70%) of the incorporated dopants are
      electrically active, therefore enabling a low sheet resistance for a given dopant
      areal dose. The wafer-scale uniformity is investigated and found to be limited by
      the temperature homogeneity of the spike anneal tool used in the experiments.
      Notably, minimal junction leakage currents (<1 microA/cm(2)) are observed that
      highlights the quality of the junctions formed by this process. The results
      clearly demonstrate the versatility and potency of the monolayer doping approach
      for enabling controlled, molecular-scale ultrashallow junction formation without
      introducing defects in the semiconductor.

PMID- 19161335
TI  - Free energy landscape of a DNA-carbon nanotube hybrid using replica exchange
      molecular dynamics.
AB  - The DNA-carbon nanotube hybrid (DNA-CN) consists of a single-wall carbon nanotube
      (SWCN) coated with a self-assembled monolayer of single-stranded DNA (ssDNA).
      Recent experiments have demonstrated that this nanomaterial is ideal for numerous
      nanotechnological applications. Despite this importance, the structure of this
      material remains poorly understood. Molecular dynamics (MD) simulations have
      provided information about the self-assembly mechanisms and ssDNA conformations
      that characterize DNA-CN. However, MD simulations of biopolymers at low
      temperatures (T approximately 300 K) result in kinetic trapping that limits
      conformational sampling. Here, we present results of a large-scale replica
      exchange molecular dynamics (REMD) simulation that provides extensive sampling of
      the entire ensemble of oligonucleotide conformations in a (GT)(7)-SWCN hybrid. We
      calculate the free energy landscape and find minima corresponding to six distinct
      conformations, with a nonhelical loop structure as the global minimum. The hybrid
      contains significant structural disorder, with desorbed bases as an important
      structural feature. These results expand our understanding of DNA-CN and indicate
      the relevance of REMD for explorations of the physical properties of organic
      inorganic multifunctional nanomaterials.

PMID- 19161336
TI  - Development of synthetic methodology suitable for the radiosynthesis of
      combretastatin A-1 (CA1) and its corresponding prodrug CA1P.
AB  - Synthetic methodology has been established suitable for the preparation of
      combretastatin A-1 (CA1) and its corresponding phosphate prodrug salt (CA1P) in
      high specific activity radiolabeled form. Judicious selection of appropriate
      phenolic protecting groups to distinguish positions on the A-ring from the B-ring
      of the stilbenoid was paramount for the success of this project. Methylation of
      the C-4' phenolic moiety by removal of the tert-butyldimethylsilyl protecting
      group in the presence of methyl iodide was accomplished in excellent yield
      without significant Z to E isomerization. This step (carried out with (12)C
      methyl iodide as proof of concept in this study) represents the process in which
      a (14)C radioisotope could be incorporated in an actual radiosynthesis. CA1 is a
      natural product isolated from the African bush willow tree (Combretum caffrum)
      that has important medicinal value due, in part, to its ability to inhibit
      tubulin assembly. As a prodrug, CA1P (OXi4503) is in human clinical trials as a
      vascular disrupting agent.

PMID- 19161337
TI  - Dissociation of the subunits of the calcium-independent receptor of alpha
      latrotoxin as a result of two-step proteolysis.
AB  - CIRL (the calcium-independent receptor of alpha-latrotoxin), a neuronal cell
      surface receptor implicated in the regulation of exocytosis, is a member of the
      GPS family of chimeric cell adhesion/G protein-coupled receptors. The predominant
      form of CIRL is a membrane-bound complex of two subunits, p120 and p85.
      Extracellularly oriented p120 contains hydrophilic cell adhesion domains, whereas
      p85 is a heptahelical membrane protein. Both subunits are encoded by the same
      gene and represent products of intracellular proteolytic processing of the CIRL
      precursor. In this study, we demonstrate that a soluble form of CIRL also exists
      in vitro and in vivo. It results from the further cleavage of CIRL by a second
      protease. The site of the second cleavage is located in the short N-terminal
      extracellular tail of p85, between the GPS domain and the first transmembrane
      segment of CIRL. Thus, the soluble form of CIRL represents a complex of p120
      noncovalently bound to a 15 amino acid residue N-terminal peptide fragment of
      p85. We have previously shown that mutations of CIRL in the GPS domain inhibit
      intracellular proteolytic processing and also result in the absence of the
      receptors from the cell surface. Our current data suggest that although CIRL
      trafficking to the cell membrane is impaired by mutations in the GPS region, it
      is not blocked completely. However, at the cell surface, the noncleaved mutants
      are preferentially targeted by the second protease that sheds the extracellular
      subunit. Therefore, the two-step proteolytic processing may represent a
      regulatory mechanism that controls cell surface expression of membrane-bound and
      soluble forms of CIRL.

PMID- 19161339
TI  - Crystal structures of MEK1 binary and ternary complexes with nucleotides and
      inhibitors.
AB  - MEK1 is a member of the MAPK signal transduction pathway that responds to growth
      factors and cytokines. We have determined that the kinase domain spans residues
      35-382 by proteolytic cleavage. The complete kinase domain has been crystallized
      and its X-ray crystal structure as a complex with magnesium and ATP-gammaS
      determined at 2.1 A. Unlike crystals of a truncated kinase domain previously
      published, the crystals of the intact domain can be grown either as a binary
      complex with a nucleotide or as a ternary complex with a nucleotide and one of a
      multitude of allosteric inhibitors. Further, the crystals allow for the
      determination of costructures with ATP competitive inhibitors. We describe the
      structures of nonphosphorylated MEK1 (npMEK1) binary complexes with ADP and
      K252a, an ATP-competitive inhibitor (see Table 1), at 1.9 and 2.7 A resolution,
      respectively. Ternary complexes have also been solved between npMEK1, a
      nucleotide, and an allosteric non-ATP competitive inhibitor: ATP-gammaS with
      compound 1 and ADP with either U0126 or the MEK1 clinical candidate PD325089 at
      1.8, 2.0, and 2.5 A, respectively. Compound 1 is structurally similar to
      PD325901. These structures illustrate fundamental differences among various
      mechanisms of inhibition at the molecular level. Residues 44-51 have previously
      been shown to play a negative regulatory role in MEK1 activity. The crystal
      structure of the integral kinase domain provides a structural rationale for the
      role of these residues. They form helix A and repress enzymatic activity by
      stabilizing an inactive conformation in which helix C is displaced from its
      active state position. Finally, the structure provides for the first time a
      molecular rationale that explains how mutations in MEK may lead to the cardio
      facio-cutaneous syndrome.

PMID- 19161338
TI  - TbetaR-II discriminates the high- and low-affinity TGF-beta isoforms via two
      hydrogen-bonded ion pairs.
AB  - The TGF-beta isoforms, TGF-beta1, -beta2, and -beta3, share greater than 70%
      sequence identity and are almost structurally identical. TGF-beta2 differs from
      the others, however, in that it binds the TGF-beta type II receptor (TbetaR-II)
      with much lower affinity than either TGF-beta1 or -beta3. It has been previously
      shown that three conserved interfacial residues, Arg25, Val92, Arg94, in TGF
      beta1 and -beta3 are responsible for their high-affinity interaction with TbetaR
      II. In this study, the role of each of these residues was examined by creating
      single, double, and triple substitutions resulting in both TGF-beta3 loss-of
      function and TGF-beta2 gain-of-function variants. One-dimensional 1H NMR spectra
      of the variants confirmed a lack of large structural perturbations. Affinities,
      kinetics, and thermodynamics for TbetaR-II binding were determined by surface
      plasmon resonance biosensor analysis. Double substitutions revealed that nearly
      all of the high-affinity binding is contributed by Arg25 and Arg94. Single site
      substitutions showed that Arg94 makes the greatest contribution. Substitution of
      Arg25 and Arg94 with alanine verified the requirement of the arginine guanidinium
      functional groups for the highly specific hydrogen-bonded ion pairs formed
      between Arg25 and Arg94 of TGF-beta1 and -beta3, and Glu119 and Asp32 of TbetaR
      II. Further kinetic and thermodynamic analyses confirmed that Arg25 and Arg94 are
      primarily responsible for high-affinity binding and also revealed that
      noninterfacial longer range effects emanating from the TGF-beta structural
      framework contribute slightly to TbetaR-II binding. Growth inhibition assays
      showed that binding changes generally correlate directly with changes in
      function; however, a role Val92 in this cellular context was uncovered.

PMID- 19161341
TI  - N-->S acyl-transfer-mediated synthesis of peptide thioesters using anilide
      derivatives.
AB  - N-->S acyl-transfer-mediated synthesis of peptide thioesters utilizing an N
      aminoacyl-N-sulfanylethylaminobenzoic acid derivative has been examined. The
      developed synthetic methodology for peptide thioesters is compatible with Fmoc
      solid-phase peptide synthesis (SPPS).

PMID- 19161340
TI  - Synthesis of potential early-stage intermediates in the biosynthesis of FR900482
      and mitomycin C.
AB  - Beyond the identification of 3-amino-5-hydroxybenzoic acid (AHBA) and D
      glucosamine as biosynthetic precursors to mitomycin C (5) and FR900482 (6),
      little is known about the pathway Nature uses to prepare these antitumor
      antibiotics. To gain some insight into their biosynthesis, amino acids 1 and 2 as
      well as C-2 N-acetylated derivatives 3 and 4 were prepared. Preparation of these
      putative biosynthetic intermediates and N-acetylcysteamine thioester analogues 28
      and 29 should enable confirmation of their involvement in FR900482 and mitomycin
      C biosynthesis.

PMID- 19161342
TI  - High-performance immunolatex possessing a mixed-PEG/antibody coimmobilized
      surface: highly sensitive ferritin immunodiagnostics.
AB  - To create a high-performance immunoassay system based on a nanosphere/antibody
      complex, pentaethylenehexamine-ended poly(ethylene glycol), N6-PEG comprising N6
      PEG-5k (M(n) = 6000 g/mol) and N6-PEG-2k (M(n) = 2000 g/mol) was employed as a
      novel blocking agent to modify the surface of nanospheres. Both the antibody
      (antiferritin) and the N6-PEG were covalently bonded onto the nanospheres by the
      linkage of their amino groups with the activated carboxyl groups of those
      particles. The quantification of antiferritin and tethered N6-PEG polymer was
      carried out using the copper reduction/bicinchoninic acid reaction (the Micro BCA
      method). Dynamic-light-scattering (DLS) and electrophoretic mobility (mu(e))
      measurements were performed to characterize the nanosphere/antiferritin/N6-PEG
      complex, which was prepared under various conditions. Simultaneously, the immune
      response of the complex obtained in this manner was measured by the turbidimetric
      monitoring method in phosphate buffer (10 mM, pH = 7.4). On the basis of all the
      results, the optimum conditions for preparing an acceptable
      nanosphere/antiferritin/N6-PEG complex were determined. Interestingly, compared
      to the blocking treatment with bovine serum albumin (BSA), which is a well-known
      blocking agent, surface modification with N6-PEG, especially that using a mixture
      of N6-PEG-5k and N6-PEG-2k, improved the performance (increased immune response
      yield and decreased detection limit) of the nanosphere/antiferritin complex to a
      remarkable degree in both phosphate buffer and 100% fetal bovine serum (FBS),
      thus significantly demonstrating the potential of the nanosphere/antibody/mixed
      PEG complex as central to a high-performance immunoassay system.

PMID- 19161345
TI  - Diterpenoid Alkaloids from Delphinium majus.
AB  - From the whole herbs of Delphinium majus, three new C(19)-diterpenoid alkaloids,
      majusines A-C (1-3), and six new C(20)-diterpenoid alkaloids, majusimines A-D (4
      7) and majusidine A and B (8 and 9), have been isolated, together with 15 known
      compounds. The structures of compounds 1-9 were elucidated by spectroscopic data
      interpretation.

PMID- 19161344
TI  - Antimalarial peptides from marine cyanobacteria: isolation and structural
      elucidation of gallinamide A.
AB  - As part of a continuing program to identify novel treatments for neglected
      parasitic diseases, the Panama International Cooperative Biodiversity Group
      (ICBG) program has been investigating the antimalarial potential of secondary
      metabolites from Panamanian marine cyanobacteria. From over 60 strains of
      cyanobacteria evaluated in our biological screens, the organic extract of a
      Schizothrix species from a tropical reef near Piedras Gallinas (Caribbean coast
      of Panama) showed potent initial antimalarial activity against the W2 chloroquine
      resistant strain of Plasmodium falciparum. Bioassay-guided fractionation followed
      by 2D NMR analysis afforded the planar structure of a new and highly
      functionalized linear peptide, gallinamide A. Subsequent degradation and
      derivatization methods were used to determine the absolute configuration at most
      stereogenic centers in this unusual new metabolite.

PMID- 19161346
TI  - The second-meal phenomenon is associated with enhanced muscle glycogen storage in
      humans.
AB  - The rise in blood glucose after lunch is less if breakfast has been eaten. The
      metabolic basis of this second-meal phenomenon remains uncertain. We hypothesized
      that storage of ingested glucose as glycogen could be responsible during the post
      meal suppression of plasma NEFAs (non-esterified fatty acids; 'free' fatty
      acids). In the present study we determined the metabolic basis of the second-meal
      phenomenon. Healthy subjects were studied on two separate days, with breakfast
      and without breakfast in a random order. We studied metabolic changes after a
      standardized test lunch labelled with 3 g of 13C-labelled (99%) glucose. Changes
      in post-prandial muscle glycogen storage were measured using 13C magnetic
      resonance spectroscopy. The rise in plasma glucose after lunch was significantly
      less if breakfast had been taken (0.9+/-0.3 compared with 3.2+/-0.3 mmol/l, with
      and without breakfast respectively; P<0.001), despite comparable insulin
      responses. Pre-lunch NEFAs were suppressed after breakfast (0.13+/-0.03 compared
      with 0.51+/-0.04 mmol/l) and levels correlated positively with the maximum
      glucose rise after lunch (r=0.62, P=0.001). The increase in muscle glycogen
      signal was greater 5 h after lunch on the breakfast day (103+/-21 compared with
      48+/-12 units; P<0.007) and correlated negatively with plasma NEFA concentrations
      before lunch (r=-0.48, P<0.05). The second-meal effect is associated with priming
      of muscle glycogen synthesis consequent upon sustained suppression of plasma NEFA
      concentrations.

PMID- 19161347
TI  - The permissive role of mitochondria in the induction of haem oxygenase-1 in
      endothelial cells.
AB  - HO-1 (haem oxygenase 1) is an essential antioxidant enzyme in the cell that
      exerts its effects through removal of pro-oxidant haem groups and the formation
      of antioxidant molecules and carbon monoxide. The electrophilic cyclopentenone
      15d-PGJ2 (15-deoxy-Delta(12,14)-prostaglandin J2) induces the expression of HO-1
      protein through the covalent modification of protein thiols. It has been shown
      that specific thiol residues of the redox-sensor Keap1 (Kelch-like ECH-associated
      protein 1) are modified by 15d-PGJ2, leading to activation of the transcription
      factor Nrf-2 (nuclear factor-erythroid 2 p45 subunit-related factor 2) and up
      regulation of genes under control of the electrophile-response element, including
      HO-1. However, 15d-PGJ2 has also been shown to modify other proteins which
      comprise the electrophile-responsive proteome. Since 15d-PGJ2 has been shown to
      localize to the mitochondria in endothelial cells, we hypothesized that
      mitochondrial protein modification may also be important in Keap1/Nrf-2 signal
      transduction, leading to HO-1 up-regulation. In order to determine the role of
      mitochondrial protein thiol modification in HO-1 induction, we used the
      mitochondrial-targeted thiol-reactive compound IBTP [(4
      iodobutyl)triphenylphosphonium]. IBTP had no effect on basal HO-1 levels, but
      effectively blocked HO-1 induction by a variety of reagents including haemin,
      iodoacetamide and 15d-PGJ2. Mechanistically, IBTP did not prevent the covalent
      modification of Keap1 by 15d-PGJ2. However, IBTP prevented the 15d-PGJ2-dependent
      increases in HO-1 mRNA and protein. Furthermore, IBTP prevented the nuclear
      accumulation of Nrf-2, suggesting cross-talk between mitochondria and antioxidant
      response signal transduction. This effect was independent of reactive oxygen
      species formation or mitochondrial membrane potential. In addition, IBTP
      significantly enhanced the toxicity of high concentrations of 15d-PGJ2,
      suggesting that loss of mitochondrial control of HO-1 leads to increased
      susceptibility to electrophilic stress in endothelial cells. The implications for
      these studies in understanding the balance between cytoprotection and
      cytotoxicity in the context of diseases such as atherosclerosis is discussed.

PMID- 19161348
TI  - Teratosphaeria nubilosa, a serious leaf disease pathogen of Eucalyptus spp. in
      native and introduced areas.
AB  - BACKGROUND: Teratosphaeria nubilosa is a serious leaf pathogen of several
      Eucalyptus spp. This review considers the taxonomic history, epidemiology, host
      associations and molecular biology of T. nubilosa. TAXONOMY: Kingdom Fungi;
      Phylum Ascomycota; Class Dothideomycetes; Order Capnodiales; Family
      Teratosphaeriaceae; genus Teratosphaeria; species nubilosa. IDENTIFICATION:
      Pseudothecia hypophyllous, less so amphigenous, ascomata black, globose becoming
      erumpent, asci aparaphysate, fasciculate, bitunicate, obovoid to ellipsoid,
      straight or incurved, eight-spored, ascospores hyaline, non-guttulate, thin
      walled, straight to slightly curved, obovoid with obtuse ends, medially one
      septate, slightly constricted at the median septum, tapering to both ends,
      ascospore germination type F, germinating from both ends, germ tubes growing
      parallel to the long axis of the spore with distortion of the primary ascospore
      cell. HOST RANGE: Teratosphaeria nubilosa is a primary pathogen of several
      Eucalyptus spp., including E. botryoides, E. bicostata, E. bridgesiana, E.
      cypellocarpa, E. dunnii, E. globulus ssp. bicostata, E. globulus ssp. globulus,
      E. globulus ssp. maidenii, E. globulus ssp. pseudoglobulus, E. grandis, E.
      gunnii, E. nitens, E. pilularis, E. quadrangulata, E. viminalis, E. grandis x E.
      resinifera and E. urophylla x E. globulus. DISEASE SYMPTOMS: Leaf spots
      predominantly occur on juvenile Eucalyptus foliage; however, T. nubilosa has also
      recently been found on mature Eucalyptus foliage. Leaf spots are amphigenous,
      varying in size from small spots that are round to irregular. Lesions enlarge and
      coalesce to form larger blotches over the leaf surface. Initial lesions appear as
      pale-green spots surrounded by purple margins and, once mature, are generally
      yellow to pale brown with dark-brown raised borders. USEFUL WEBSITES: Mycobank,
      http://www.mycobank.org; Mycosphaerella identification website,
      http://www.cbs.knaw.nl/mycosphaerella/BioloMICS.aspx.

PMID- 19161349
TI  - The potato StLTPa7 gene displays a complex Ca-associated pattern of expression
      during the early stage of potato-Ralstonia solanacearum interaction.
AB  - Although nonspecific lipid transfer proteins (nsLTPs) are widely expressed during
      plant defence responses to pathogens, their functions and regulation are not
      fully understood. In this article, we report the isolation of a cDNA for the new
      nsLTP, StLTPa7, from cultivated potato (Solanum tuberosum) infected with
      Ralstonia solanacearum. The cDNA was predicted to encode a type 1 nsLTP
      containing an N-terminal signal sequence and possessing the characteristic
      features of nsLTPs. A phylogenetic analysis showed that the encoded amino acid
      sequence of the nsLTP was similar to those of other previously reported plant
      nsLTPs, which contain a putative calmodulin-binding site consisting of
      approximately 12 highly conserved amino acid residues. The expression of the
      StLTPa7 gene was studied during the early stages of potato-R. solanacearum
      interaction using real-time quantitative polymerase chain reaction (qRT-PCR) and
      Northern analyses, and a complex calcium (Ca2+)-associated pattern of expression
      was observed with the following features: (i) transcripts of the StLTPa7 gene
      were systemically up-regulated by infection with R. solanacearum; (ii) the
      StLTPa7 gene was stimulated by salicylic acid, methyl jasmonate, abscisic acid
      and Ca2+; (iii) qRT-PCR showed that, during the early stage of R. solanacearum
      infection, nsLTP transcripts accumulated over a time course that paralleled that
      of Ca2+ accumulation, detected using environmental scanning electron microscopy
      and energy-dispersive X-ray (EDAX) spectrometry; and (iv) the Ca2+ channel
      blocker, ruthenium red, partially blocked R. solanacearum-induced StLTPa7
      expression. This report represents the first use of EDAX analysis to establish a
      synchrony between Ca2+ accumulation and nsLTP expression in response to potato-R.
      solanacearum interactions. Collectively, these results suggest that StLTPa7 may
      be a pathogen- and Ca(2+)-responsive plant defence gene.

PMID- 19161350
TI  - Constitutive heterologous expression of avrXa27 in rice containing the R gene
      Xa27 confers enhanced resistance to compatible Xanthomonas oryzae strains.
AB  - The vascular pathogen Xanthomonas oryzae pv. oryzae (Xoo) and nonvascular
      pathogen Xanthomonas oryzae pv. oryzicola (Xoc) cause bacterial blight (BB) and
      bacterial leaf streak (BLS) diseases of rice, respectively. We have previously
      identified the avirulence gene avrXa27 from Xoo PXO99(A), which specifically
      induces the expression of the rice resistance gene Xa27, ultimately leading to
      resistance against BB disease in rice. In this study, we have generated a
      transgenic rice line (L24) that expresses avrXa27 constitutively under the
      control of the PR1 promoter, and have examined its role in the host-pathogen
      interaction. L24 is not more susceptible to BB, indicating that avrXa27 does not
      contribute to virulence. AvrXa27 retains avirulence activity in L24 and, after
      crossing with a line containing Xa27, progeny display phenotypic changes
      including inhibition of tillering, delay in flowering, stiff leaves, early leaf
      senescence and activation of pathogenesis-related (PR) genes. On challenge with a
      variety of compatible strains of Xoo and Xoc strain L8, lines with both avrXa27
      and Xa27 also show enhanced resistance to bacterial infection. The induction of
      Xa27 and subsequent inhibition of Xoc growth in Xa27 plants are observed on
      inoculation with Xoc L8 harbouring avrXa27. Our results indicate that the
      heterologous expression of avrXa27 in rice containing Xa27 triggers R gene
      specific resistance and, at the same time, confers enhanced resistance to
      compatible strains of Xoo and Xoc. The expression of AvrXa27 and related proteins
      in plants has the potential to generate broad resistance in plants.

PMID- 19161351
TI  - Grapevine fanleaf virus (GFLV)-specific antibodies confer GFLV and Arabis mosaic
      virus (ArMV) resistance in Nicotiana benthamiana.
AB  - Grapevine fanleaf virus (GFLV) is one of the most destructive pathogens of
      grapevine. In this study, we generated monoclonal antibodies binding specifically
      to the coat protein of GFLV. Antibody FL(3), which bound most strongly to GFLV
      and showed cross-reactivity to Arabis mosaic virus (ArMV), was used to construct
      the single-chain antibody fragment scFvGFLVcp-55. To evaluate the potential of
      this single-chain variable fragment (scFv) to confer antibody-mediated virus
      resistance, transgenic Nicotiana benthamiana plants were generated in which the
      scFv accumulated in the cytosol. Recombinant protein levels of up to 0.1% total
      soluble protein were achieved. The T(1) and T(2) progenies conferred partial or
      complete protection against GFLV on challenge with the viral pathogen. The
      resistance to GFLV in transgenic plants was strictly related to scFvGFLVcp-55
      accumulation levels, confirming that the antibody fragment was functional in
      planta and responsible for the GFLV resistance. In addition, transgenic plants
      conferring complete protection to GFLV showed substantially enhanced tolerance to
      ArMV. We demonstrate the first step towards the control of grapevine fanleaf
      degeneration, as scFvGFLVcp-55 could be an ideal candidate for mediating
      nepovirus resistance.

PMID- 19161352
TI  - Nuclear magnetic resonance characterization of metabolite disorder in orange
      trees caused by citrus sudden death disease.
AB  - Citrus sudden death (CSD) is a new disease of sweet orange and mandarin trees
      grafted on Rangpur lime and Citrus volkameriana rootstocks. It was first seen in
      Brazil in 1999, and has since been detected in more than four million trees. The
      CSD causal agent is unknown and the current hypothesis involves a virus similar
      to Citrus tristeza virus or a new virus named Citrus sudden death-associated
      virus. CSD symptoms include generalized foliar discoloration, defoliation and
      root death, and, in most cases, it can cause tree death. One of the unique
      characteristics of CSD disease is the presence of a yellow stain in the rootstock
      bark near the bud union. This region also undergoes profound anatomical changes.
      In this study, we analyse the metabolic disorder caused by CSD in the bark of
      sweet orange grafted on Rangpur lime by nuclear magnetic resonance (NMR)
      spectroscopy and imaging. The imaging results show the presence of a large amount
      of non-functional phloem in the rootstock bark of affected plants. The
      spectroscopic analysis shows a high content of triacylglyceride and sucrose,
      which may be related to phloem blockage close to the bud union. We also propose
      that, without knowing the causal CSD agent, the determination of oil content in
      rootstock bark by low-resolution NMR can be used as a complementary method for
      CSD diagnosis, screening about 300 samples per hour.

PMID- 19161353
TI  - Chimeras between oilseed rape mosaic virus and tobacco mosaic virus highlight the
      relevant role of the tobamoviral RdRp as pathogenicity determinant in several
      hosts.
AB  - Oilseed rape mosaic virus (ORMV) is a tobamovirus taxonomically distinct from the
      type member of the genus, Tobacco mosaic virus (TMV). Both viruses display a
      specific host range, although they share certain hosts, such as Arabidopsis
      thaliana, Nicotiana benthamiana and N. tabacum, on which they induce different
      symptoms. Using a gain-of-symptom approach, we generated chimeric viruses,
      starting from a TMV infectious clone, over which different regions of ORMV were
      exchanged with their corresponding regions in the TMV genome. This approach
      allowed the association of pathogenicity determinants to certain genes within the
      ORMV genome. A general trend was observed associating the viral origin of the RNA
      dependent RNA-polymerase (RdRp) gene and the gain of symptoms. In A. thaliana and
      N. benthamiana, chimeric viruses were unable to reproduce the symptoms induced by
      the parental viruses, leading to disease states which could be described as
      intermediate, and variable in some cases. In contrast, a hypersensitive reaction
      caused by both of these viruses on N-gene-bearing tobaccos could be found in
      resistance reactions to all chimeric viruses, suggesting that the avirulence
      determinant maps similarly in both viruses. A systemic necrotic spotting typical
      of non-N-gene tobaccos infected with ORMV was associated with the polymerase
      domain of RdRp. To our knowledge, this is the first time that this controversial
      portion of the tobamovirus genome has been identified directly as a pathogenicity
      determinant. None of the reactions of the chimeric viruses could be correlated
      with increases or decreases in virus titres in the infections.

PMID- 19161354
TI  - Identification of new type III effectors and analysis of the plant response by
      competitive index.
AB  - In recent years, many efforts have been directed towards the identification of
      new type III-secreted effectors, and the completion of the secretomes of several
      Pseudomonas syringae pathovars. Several functional and bioinformatic screenings
      have been used to search for candidates, which have been tested for translocation
      into the plant cell, an essential criterion for the identification of new type
      III effector proteins. The most common translocation assay is based on the use of
      DeltaAvrRpt2 as a reporter. When fused to a type III effector protein,
      DeltaAvrRpt2 is translocated and elicits a hypersensitive response in leaves of
      Arabidopsis thaliana expressing the RPS2 resistance protein. This approach has
      been used widely and has allowed the identification of a considerable number of
      new effectors in a fast and convenient manner. However, as the hypersensitive
      response is a semi-quantitative assay, and the conditions do not resemble those
      occurring in nature, effectors with low expression or translocation efficiency
      could fail to translocate sufficient DeltaAvrRpt2 to trigger a clear
      hypersensitive response. In keeping with these limitations, this test has failed
      to detect some true effectors that have been confirmed as such by other means. In
      order to increase the sensitivity of this method, we have developed a
      modification of the DeltaAvrRpt2-based translocation assay using a competitive
      index in mixed infection to monitor the limitation of growth associated with the
      induction of the hypersensitive response. We have tested several effector
      candidates from P. syringae pv. phaseolicola and other P. syringae pathovars, and
      have compared the results obtained by our competitive index translocation assay
      with those obtained by standard hypersensitive response assays. We have
      identified six type III secretion system-translocated proteins using this
      approach, five of which failed to be identified by hypersensitive response
      assays. In addition, we have analysed the defence response triggered by one of
      these effectors using competitive index assays.

PMID- 19161355
TI  - The Magnaporthe grisea class VII chitin synthase is required for normal
      appressorial development and function.
AB  - The plant pathogenic fungus Magnaporthe grisea is able to enter its host via
      appressorium-mediated penetration. Earlier investigations have shown that these
      infection structures are rich in the cell wall polysaccharide chitin. Previously,
      we have described how the transcription of a class VII chitin synthase-encoding
      gene CHS7 is completely dependent on the putative transcription factor Con7p
      during the germination of conidia, and how con7(-) mutants are unable to form
      appressoria under any conditions tested. Because of the pleiotropic effects of
      the con7(-) mutation, we examined the consequences of the targeted deletion of
      CHS7. The chs7(-) mutants generated were unable to form appressoria on artificial
      surfaces, except following the application of the exogenous inducers 1,16
      hexadecanediol and cyclic adenosine monophosphate. The appressoria formed had a
      reduced chitin content and were often found to be smaller and misshapen compared
      with the wild-type. chs7(-) mutants were significantly reduced in their ability
      to enter rice plants, but growth in planta was not affected. Reverse
      transcriptase-polymerase chain reaction analysis demonstrated that CHS7
      transcription was strongly induced on germination of spores, and a green
      fluorescent protein-tagged Chs7p protein was found to be produced abundantly
      during infection-related morphogenesis. Together, these data suggest that the
      class VII chitin synthase Chs7p of M. grisea is required for normal appressorium
      formation and function.

PMID- 19161356
TI  - Identification of virulence genes in Fusarium oxysporum f. sp. lycopersici by
      large-scale transposon tagging.
AB  - Forward genetic screens are efficient tools for the dissection of complex
      biological processes, such as fungal pathogenicity. A transposon tagging system
      was developed in the vascular wilt fungus Fusarium oxysporum f. sp. lycopersici
      by inserting the novel modified impala element imp160::gfp upstream of the
      Aspergillus nidulans niaD gene, followed by transactivation with a constitutively
      expressed transposase. A collection of 2072 Nia(+) revertants was obtained from
      reporter strain T12 and screened for alterations in virulence, using a rapid
      assay for invasive growth on apple slices. Seven strains exhibited reduced
      virulence on both apple slices and intact tomato plants. Five of these were true
      revertants showing the re-insertion of imp160::gfp within or upstream of
      predicted coding regions, whereas the other two showed either excision without re
      insertion or no excision. Linkage between imp160::gfp insertion and virulence
      phenotype was determined in four transposon-tagged loci using targeted deletion
      in the wild-type strain. Knockout mutants in one of the genes, FOXG_00016,
      displayed significantly reduced virulence, and complementation of the original
      revertant with the wild-type FOXG_00016 allele fully restored virulence.
      FOXG_00016 has homology to the velvet gene family of A. nidulans. The high rate
      of untagged virulence mutations in the T12 reporter strain appears to be
      associated with increased genetic instability, possibly as a result of the
      transactivation of endogenous transposable elements by the constitutively
      expressed transposase.

PMID- 19161357
TI  - Involvement of the cylindrical inclusion (CI) protein in the overcoming of an
      eIF4E-mediated resistance against Lettuce mosaic potyvirus.
AB  - The capacity of Lettuce mosaic virus to overcome the lettuce resistance conferred
      by the mo1(1) and mo1(2) alleles of the gene for eukaryotic translation
      initiation factor 4E (eIF4E) was analysed using reverse genetics. Mutations in
      the virus genome-linked protein (VPg) allowed mo1(1) only to be overcome, but
      mutations in the C-terminal portion of the cylindrical inclusion (CI) protein
      allowed both alleles to be overcome. Site-directed mutagenesis pinpointed a key
      role of the amino acid at position 621 in the virulence. This is the first
      example of the involvement of a potyviral CI protein in the breaking of an eIF4E
      mediated resistance.

PMID- 19161358
TI  - Mycoviruses of filamentous fungi and their relevance to plant pathology.
AB  - Mycoviruses (fungal viruses) are reviewed with emphasis on plant pathogenic
      fungi. Based on the presence of virus-like particles and unencapsidated dsRNAs,
      mycoviruses are common in all major fungal groups. Over 80 mycovirus species have
      been officially recognized from ten virus families, but a paucity of nucleic acid
      sequence data makes assignment of many reported mycoviruses difficult. Although
      most of the particle types recognized to date are isometric, a variety of
      morphologies have been found and, additionally, many apparently unencapsidated
      dsRNAs have been reported. Until recently, most characterized mycoviruses have
      dsRNA genomes, but ssRNA mycoviruses now constitute about one-third of the total.
      Two hypotheses for the origin of mycoviruses of plant pathogens are discussed:
      the first that they are of unknown but ancient origin and have coevolved along
      with their hosts, the second that they have relatively recently moved from a
      fungal plant host into the fungus. Although mycoviruses are typically readily
      transmitted through asexual spores, transmission through sexual spores varies
      with the host fungus. Evidence for natural horizontal transmission has been
      found. Typically, mycoviruses are apparently symptomless (cryptic) but beneficial
      effects on the host fungus have been reported. Of more practical interest to
      plant pathologists are those viruses that confer a hypovirulent phenotype, and
      the scope for using such viruses as biocontrol agents is reviewed. New tools are
      being developed based on host genome studies that will help to address the
      intellectual challenge of understanding the fungal-virus interactions and the
      practical challenge of manipulating this relationship to develop novel biocontrol
      agents for important plant pathogens.

PMID- 19161359
TI  - Progress towards the understanding and control of sugar beet rhizomania disease.
AB  - Rhizomania is a soil-borne disease that occurs throughout the major sugar beet
      growing regions of the world, causing severe yield losses in the absence of
      effective control measures. It is caused by Beet necrotic yellow vein virus
      (BNYVV), which is transmitted by the obligate root-infecting parasite Polymyxa
      betae. BNYVV has a multipartite RNA genome with all natural isolates containing
      four RNA species, although some isolates have a fifth RNA. The larger RNA1 and
      RNA2 contain the housekeeping genes of the virus and are always required for
      infection, whereas the smaller RNAs are involved in pathogenicity and vector
      transmission. RNA5-containing isolates are restricted to Asia and some parts of
      Europe, and these isolates tend to be more aggressive. With no acceptable
      pesticides available to restrict the vector, the control of rhizomania is now
      achieved almost exclusively through the use of resistant cultivars. A single
      dominant resistance gene, Rz1, has been used to manage the disease worldwide in
      recent years, although this gene confers only partial resistance. More recently,
      new variants of BNYVV have evolved (both with and without RNA5) that are able to
      cause significant yield penalties on resistant cultivars. These isolates are not
      yet widespread, but their appearance has resulted in accelerated searches for new
      sources of resistance to both the virus and the vector. Combined virus and vector
      resistance, achieved either by conventional or transgenic breeding, offers the
      sugar beet industry a new approach in its continuing struggle against rhizomania.

PMID- 19161360
TI  - Horizontal gene transfer: sustaining pathogenicity and optimizing host-pathogen
      interactions.
AB  - Successful host-pathogen interactions require the presence, maintenance and
      expression of gene cassettes called 'pathogenicity islands' (PAIs) and 'metabolic
      islands' (MAIs) in the respective pathogen. The products of these genes confer on
      the pathogen the means to recognize their host(s) and to efficiently evade host
      defences in order to colonize, propagate within the host and eventually
      disseminate from the host. Virulence effectors secreted by type III and type IV
      secretion systems, among others, play vital roles in sustaining pathogenicity and
      optimizing host-pathogen interactions. Complete genome sequences of plant
      pathogenic bacteria have revealed the presence of PAIs and MAIs. The genes of
      these islands possess mosaic structures with regions displaying differences in
      nucleotide composition and codon usage in relation to adjacent genome structures,
      features that are highly suggestive of their acquisition from a foreign donor.
      These donors can be other bacteria, as well as lower members of the Archaea and
      Eukarya. Genes that have moved from the domains Archaea and Eukarya to the domain
      Bacteria are true cases of horizontal gene transfer. They represent interdomain
      genetic transfer. Genetic exchange between distinct members of the domain
      Bacteria, however, represents lateral gene transfer, an intradomain event. Both
      horizontal and lateral gene transfer events have been used to facilitate survival
      fitness of the pathogen.

PMID- 19161362
TI  - Ability of low-molecular-weight heparin to alleviate proteinuria by inhibiting
      respiratory syncytial virus infection.
AB  - AIM: Low-molecular-weight heparin (LMWH) is a negatively charged glycoprotein and
      has a very similar structure to that of cell surface heparin sulfate (HS). Thus,
      LMWH, an analog of HS, may inhibit positively charged respiratory syncytial virus
      (RSV) infection through cooperative electrostatic association. METHODS: In this
      study, rats were respectively treated with 400 IU/kg LMWH before, during or after
      being inoculated with 6 x 10(6) plaque-forming unit (PFU) RSV. RSV and normal
      control groups were respectively inoculated by RSV and virus-free Dulbecco's
      modified Eagle's medium (DMEM). HeLa cells in vitro were pretreated with LMWH,
      elastase (ELA), heparinase (HpaIII) and protamine before being inoculated with 6
      x 10(1) PFU RSV. RSV infectivity was determined by in situ hybridization and
      plaque assay. RESULTS: After inoculation, the urinary protein excretion and serum
      parameters in LMWH-treated rats were significantly lower than those in the RSV
      group. No abnormalities of glomerular structure were observed in LMWH-treated
      groups whereas swelling and slight hypercellularity in minority glomeruli and
      foot process effacement were observed in the RSV group. RSV RNA of LMWH-treated
      rats had weaker expression than that of the RSV group. In vitro, RSV infection in
      RSV + LMWH, HpaIII + ELAI, protamine + ELAI, ELAI, HpaIII and protamine treatment
      cells were significantly lower than that of the RSV control, and that in RSV +
      LMWH was the least. There were no significant differences in RSV infection
      between ELAI + LMWH and RSV control. CONCLUSION: Our study confirmed that there
      is a correlation between RSV and proteinuria in rats. LMWH can alleviate
      proteinuria in rats through inhibiting RSV from binding with HS which plays an
      important role in the onset of RSV infection.

PMID- 19161363
TI  - Review article: Tackling the survival issue in end-stage renal disease: time to
      get physical on haemodialysis.
AB  - Life expectancy in haemodialysis patients is reduced fourfold on average versus
      healthy age-matched individuals. The purpose of this review is to present
      empirical evidence that intradialytic exercise can mitigate primary independent
      risk factors for early mortality in end-stage renal disease. These risk factors
      include measures of skeletal muscle wasting, systemic inflammation,
      cardiovascular functioning and dialysis adequacy. Overall, the available
      literature provides support for the integration of exercise within the
      conventional outpatient haemodialysis unit. The amelioration of various
      physiological risk factors through an appropriate exercise prescription may
      enhance survival in this vulnerable cohort. Investigations are required to
      determine the effects of various doses of intradialytic exercise on a broad range
      of clinical outcomes, and more thoroughly elucidate the relationship between
      exercise-induced adaptations and survival advantage in end-stage renal disease.

PMID- 19161364
TI  - Atherosclerosis is associated with plasminogen activator inhibitor type-1 in
      chronic haemodialysis patients.
AB  - AIM: The aim of the present report was to investigate the probable association of
      circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery
      walls with atherosclerotic disease in chronic haemodialysis (HD) patients.
      METHODS: Sixty-eight non-diabetic HD patients and 50 age- and sex-matched healthy
      normotensive controls participated in the study. Atherosclerotic disease in both
      groups was assessed by measuring intima-media thickness (IMT) and plaque score of
      the common carotid arteries using an ultrasound scanner. Levels of serum PAI-1, C
      reactive protein (CRP), interleukin (IL)-6 and lipids profile were measured.
      Internal iliac artery samples were obtained at the time of renal transplantation.
      Quantitative expression of PAI-1 in internal iliac artery walls was assessed by
      positive unit (pu) value using an immunohistochemical method. In addition, the
      IMT and carotid plaque score were analyzed in relation to circulating levels of
      PAI-1 and expression of PAI-1 in internal iliac artery walls. RESULTS: Compared
      with control subjects, HD patients had significantly increased common carotid
      artery (CCA)-IMT (P = 0.002). Atherosclerotic plaques were detected in 42
      (61.76%) of HD patients and in two (4%) controls. The above ultrasonographic
      indices were correlated with age in HD patients (P < 0.001). A significant
      relationship was observed between IMT and systolic blood pressure (BP), low
      density lipoprotein in HD patients (P < 0.001 and P < 0.001, respectively). In HD
      patients, IMT was significantly correlated with CRP and IL-6 (P < 0.001 and P <
      0.001, respectively). In HD patients, a close correlation was found between serum
      PAI-1 level, CRP and IL-6 (P < 0.01 and P < 0.01, respectively). A close
      correlation was also found between PAI-1 pu value, CRP and IL-6 (P < 0.01 and P <
      0.01 respectively). Serum PAI-1 level is highly correlated to PAI-1 pu value (P <
      0.01). In HD patients, CCA-IMT and plaque score were correlated significantly
      with circulating levels of PAI-1(P < 0.01 and P < 0.05, respectively) and
      expression of PAI-1 in internal iliac artery walls (P < 0.01 and P < 0.05,
      respectively). Multivariate analysis showed that log CRP values were a strong
      independent contributor to CCA-IMT and plaque score (P = 0.03 and P = 0.04,
      respectively). Multivariate analysis showed that serum PAI-1 concentration was a
      strong independent correlate of CCA-IMT and carotid plaque score (P = 0.004 and P
      = 0.009, respectively). Multivariate analysis also showed that expression of PAI
      1 in internal iliac artery walls was a strong independent correlate of CCA-IMT
      and carotid plaque score (P = 0.008 and P = 0.005, respectively). CONCLUSION: The
      circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery
      walls were statistically associated with CRP, IL-6 and low-density lipoprotein
      cholesterol. Moreover, in HD patients, CCA-IMT and plaque score were correlated
      significantly with circulating levels of PAI-1 and expression of PAI-1 in
      internal iliac artery walls and the circulating levels of PAI-1 and expression of
      PAI-1 in internal iliac artery walls were independent predictors of carotid
      atherosclerosis including CCA-IMT and carotid plaque score. The correlations may
      suggest that increased circulating PAI-1 level and upregulated expression of PAI
      1 in the vasculature could indicate a chronic endothelium activated state and PAI
      1 may more precisely identify the risk of atherothrombosis and be useful as a
      target for anti-inflammatory treatment strategies.

PMID- 19161365
TI  - Immediate blood pressure-lowering effects of aerobic exercise among patients with
      chronic kidney disease.
AB  - AIM: The current study was designed to determine the effect of moderate-intensity
      aerobic exercise on blood pressure responses within the laboratory for 60 min
      post exercise and in the subsequent 24 h period in patients with chronic kidney
      disease. METHODS: Twenty-four subjects with stages 2-4 chronic kidney disease
      (age = 54.5 +/- 15.2 years, body mass index = 32.0 +/- 5.9 kg/m(2)) on
      antihypertensive medication completed this study. In random counterbalanced
      order, subjects were asked to either walk for 40 min at 50-60% VO(2peak) (oxygen
      consumption) or, on a separate day, to sit quietly in the laboratory for the same
      length of time. Following exercise or the non-exercise period, blood pressure was
      taken at 10 min intervals for 60 min. Subjects then wore an ambulatory blood
      pressure monitor for the next 24 h. RESULTS: Systolic blood pressure (mmHg) was
      reduced by 6.5 +/- 10.8 compared with the pre-exercise baseline value (130.3 +/-
      21.1) in the laboratory after exercise and this was greater than after the
      control period (0.73 +/- 10.3, P < 0.05). Diastolic blood pressure (mmHg) was
      reduced following exercise (2.5 +/- 6.4) compared with the control period (2.1 +/
      4.9, P < 0.05). The mean 24 h readings did not differ between exercise or non
      exercise days. CONCLUSION: Acute aerobic exercise leads to reduced blood pressure
      for at least 60 min within the laboratory in chronic kidney disease patients.

PMID- 19161366
TI  - Microalbuminuria as a possible marker of risk of Balkan endemic nephropathy.
AB  - AIM: To evaluate whether microalbuminuria could be a marker of early tubular
      damage in individuals at risk of developing Balkan endemic nephropathy (BEN).
      METHODS: A cross-sectional study was used to determine urinary albumin-to
      creatinine ratio (UACR) in a test group of 61 participants from a BEN endemic
      region and control group of 64 participants from a nearby non-endemic region,
      both recruited from the general population of Bosnia and Herzegovina. The
      correlation between UACR and urinary b2 microglobulin-to-creatinine ratio (UBCR)
      and the receiver operating characteristic curve for UACR were analyzed in the
      test groups of 58 participants. The correlation analysis was also performed in a
      subset of nine subjects with elevated UBCR. RESULTS: Medians, interquartile
      ranges and confidence intervals (CI) for medians of UACR in the test and control
      groups were 2 mg/mmol, 0.975-8.247 mg/mmol, 1.3472-3.2691 mg/mmol and 1 mg/mmol,
      0.695-1.41 mg/mmol, 0.8466-1.2053 mg/mmol, respectively (P = 0.0001).
      Microalbuminuria was found in 30 of the 61 examinees in the test group, in
      contrast to six of the 64 examinees in the controls (P < 0.0001). Participants
      from the endemic region had 9.3 times the odds of having microalbuminuria in
      contrast to participants from the non-endemic region. Pearson's correlation
      coefficients r of the log-transformed ratios and Kendall-tau coefficients of rank
      correlation in the group of 58 and in a subset of nine subjects with elevated
      UBCR were: 0.55 (P < 0.0001); 0.317 (P = 0.0005) and 0.59 (P = 0.045); 0.48 (P =
      0.037), respectively. The area under the curve for UACR was 0.882 (P = 0.0001),
      sensitivity 100% and specificity 67.3%. CONCLUSION: Microalbuminuria may be a
      useful marker of early tubular injury in individuals at risk of developing BEN.

PMID- 19161368
TI  - Instructive case. An instructive case of severe hypomagnesemia.

PMID- 19161370
TI  - Overview: Exocytosis continues to amaze us.

PMID- 19161367
TI  - Change in live donor characteristics over the last 25 years: a single centre
      experience.
AB  - AIM: While deceased donor kidney transplantation rates have remained stagnant,
      live donor kidney transplantation (LDKT) rates have increased significantly over
      the last decade, and are now a major component of renal transplantation
      programmes worldwide. Additionally, there has been an increased utilization of
      more marginal donors, including donors who are obese, older and subjects with
      well-controlled hypertension. METHOD: A retrospective audit of all live donors at
      the Princess Alexandra Hospital Renal Transplantation unit was performed from 24
      August 1982 to 29 May 2007 to assess any change in donor characteristics over
      time. RESULTS: There were 373 live donor operations. Over the last 25 years there
      has been a significant increase in the number of donors who are either older or
      obese. Furthermore, there is a greater proportion of spousal and emotionally
      related LDKT. CONCLUSION: It is imperative that donors, in particular marginal
      donors, are followed up long-term to determine their risk of kidney and
      cardiovascular disease and initiation of appropriate treatment if required.

PMID- 19161371
TI  - Rhythmic kinetics of single fusion and fission in a plant cell protoplast.
AB  - Plant cells exhibit a lively activity of exocytosis and endocytosis at the plasma
      membrane. This is required for cell surface area regulation and also for membrane
      protein recycling. Although these processes are important for growth and
      development, they are understood purely with respect to their molecular
      mechanisms, regulation, spatial organization, and kinetics. According to the
      classical view, secretory vesicles release all their cargo in one step upon
      fusing and incorporating into the plasma membrane. Recent studies have shown that
      this model is oversimplifying the reality. Here we use real-time patch-clamp
      recording to monitor single-vesicle fusion and fission in order to resolve the
      kinetic properties of these elementary processes. The data show that single
      vesicles can, in a rhythmic fashion, make and break contact with the plasma
      membrane of plant protoplasts. Such oscillations are only possible if the two
      processes are linked by a distinct feedback system. The fact that similar
      rhythmic fusion/fission activity is also present in constitutive exocytosis in
      animal cells implies that the underlying mechanisms appear universal in
      eukaryotic cells.

PMID- 19161372
TI  - Fluorescent cargo proteins in peptidergic endocrine cells: cell type determines
      secretion kinetics at exocytosis.
AB  - Fluorescent fusion proteins are an important tool for the study of vesicle
      trafficking and exocytosis, especially when combined with newer types of
      microscopy. We previously reported that the design of a vesicle-targeted
      fluorescent fusion construct strongly influences the kinetics of fluorescence
      change at exocytosis. In the present study we demonstrate that the cell in which
      a construct is expressed also affects the kinetics of fluorescence change at
      exocytosis. We fused enhanced green fluorescent protein to the carboxy terminus
      of the vesicular cargo protein rodent islet amyloid polypeptide. The two proteins
      were separated by a "linker" sequence of 18 amino acids. We then compared
      kinetics of fluorescence change at exocytosis for this fluorescent cargo protein
      expressed in three different types of peptidergic endocrine cell: pancreatic
      alpha cell, pancreatic beta cell, and adrenal chromaffin cell. In resting cells
      of all three types, fluorescent spots of similar size and membrane-proximal
      density appeared near the plasma membrane as expected if the probe is stored in
      large dense-core secretory vesicles. Upon stimulation, the fluorescent spots
      displayed sudden changes in fluorescence intensity that were consistent with
      exocytosis. In beta and alpha cells the fluorescent spots consistently brightened
      and persisted, whereas in chromaffin cells the fluorescent spots always dispersed
      rapidly. Thus, for fluorescent cargo proteins in peptidergic endocrine cells,
      cell type influences the kinetics of fluorescence change at exocytosis. Together
      with our previous findings, this observation strongly highlights the fact that
      the behavior of vesicle-targeted fluorescent cargo may be unrelated to that of
      native cargo, and it emphasizes the need for caution in interpreting fluorescence
      kinetics in terms of an exocytosis mechanism.

PMID- 19161373
TI  - Apical plasma membrane traffic in superficial cells of bladder urothelium.
AB  - Superficial urothelial cells that line the urinary bladder accommodate cyclical
      changes in organ volume while maintaining a permeability barrier between urine
      and tissue fluids. The specific apical plasma membrane traffic is necessary for
      their proper function. The composition of the apical plasma membrane is
      dramatically modified during differentiation of bladder urothelial cells, most
      notably by assembly of urothelial plaques containing uroplakins. However, the
      assembly of uroplakins into plaques, their insertion and removal from the apical
      surface, and the regulation of these processes are still poorly understood. This
      review examines the traffic (exocytosis/endocytosis) of the apical plasma
      membrane during differentiation of urothelial cells and focuses on the
      physiological and clinical significance of the apical plasma membrane traffic in
      bladder superficial urothelial cells.

PMID- 19161374
TI  - Regulated exocytosis and vesicle trafficking in astrocytes.
AB  - Astrocytes are increasingly viewed as crucial cells supporting and integrating
      brain functions. It is thought that the release of gliotransmitters into the
      extracellular space by regulated exocytosis supports a significant part of
      communication between astrocytes and neurons. Prior to exocytosis, the membrane
      bound vesicles are transported through the astrocyte cytoplasm. Our recent
      studies have revealed new insights into vesicle trafficking in the cytoplasm of
      astrocytes and are reviewed in this article. The prefusion mobility of
      fluorescently labeled peptidergic vesicles was studied in cultured rat and mouse
      astrocytes. Vesicle delivery to the plasma membrane involved an interaction with
      the cytoskeleton, in particular with microtubules and actin filaments.
      Interestingly, vesicle mobility in mouse astrocytes deficient in intermediate
      filaments show impaired directionality of peptidergic vesicle mobility. To
      explore whether stimuli that increase the concentration of free calcium ions in
      the cytoplasm triggered vesicular ATP release from astrocytes, human embryonic
      kidney-293T cells transfected with a P2X(3) receptor were used as sniffers to
      detect ATP release. Glutamate stimulation of astrocytes was followed by an
      increase in the incidence of small, transient, inward currents in sniffer cells,
      reminiscent of postsynaptic quantal events observed at synapses. Some of the
      membrane-bound vesicles are retrieved from the plasma membrane to be recycled
      back into the cytosol. Trafficking velocity of postfusion (recycling) atrial
      natriuretic peptide vesicles was one order of magnitude slower in comparison to
      the mobility of prefusion vesicles. However, transport of all vesicle types
      studied required an intact cytoskeleton.

PMID- 19161375
TI  - Ca2+-dependent actin coating of lamellar bodies after exocytotic fusion: a
      prerequisite for content release or kiss-and-run.
AB  - Type II pneumocytes secrete surfactant, a lipoprotein-like substance reducing the
      surface tension in the lung, by regulated exocytosis of secretory vesicles termed
      lamellar bodies (LBs). This secretory process is characterized by a protracted
      postfusion phase in which fusion pores open slowly and may act as mechanical
      barriers for release. Combining dark-field with fluorescence microscopy, we show
      in ss-actin green fluorescent protein-transfected pneumocytes that LB fusion with
      the plasma membrane is followed by actin coating of the fused LB. This is
      inhibited by cytoplasmic Ca(2+) chelation or the phospholipase D inhibitor C2
      ceramide. Actin coating occurs by polymerization of actin monomers, as evidenced
      by staining with Alexa 568 phalloidin. After actin coating of the fused LB, it
      either shrinks while releasing surfactant ("kiss-coat-and-release"), remains in
      this fused state without further action ("kiss-coat-and-wait"), or is retrieved
      and pushed forward in the cell on top of an actin tail ("kiss-coat-and-run"). In
      the absence of actin coating, no release or run was observed. These data suggest
      that actin coating creates a force needed for either extrusion of vesicle
      contents or retrieval and intracellular propulsion.

PMID- 19161376
TI  - Exocytosis of insulin: in vivo maturation of mouse endocrine pancreas.
AB  - The aim of this study was to define when an insulin-positive cell becomes
      functional in vivo and starts to exocytose insulin in a regulated nutrient
      dependent manner. Insulin-positive cells appear in embryonic life (midgestation)
      and complete their maturation, presumably around birth. In order to work with
      embryonic and newborn endocrine pancreas, we used organotypic slices. The mouse
      embryonic pancreas slices show high basal insulin release that is not further
      elevated by high glucose levels. Despite the presence of functional voltage
      activated ion channels, the cells are not electrically active in the presence of
      secretagogues. At birth, the high basal insulin release drops and, after
      postnatal day 2, the insulin-positive cells show both adult-like bursting
      electrical activity and hormone release induced by high glucose levels. These
      properties allowed us to define them as beta cells. Despite the apparent
      stability of the transcription factor profile reported in insulin-positive cells
      during late-embryonic life, functional beta cells appear only 2 days after birth.

PMID- 19161377
TI  - Compound exocytosis in pituitary cells.
AB  - Neurotransmitter and hormone release from vesicles involves fusion between the
      vesicle and the plasma membranes, a process termed exocytosis. Recently we
      reported that most of the spontaneous and stimulated exocytotic events in
      pituitary lactotrophs are transient and repetitive, appearing in bursts lasting
      more than 100 s. However, whether this is also the case in compound vesicle-to
      vesicle exocytosis is unknown. Here we investigated compound exocytotic events in
      resting and stimulated lactotrophs by using optical and cell-attached patch-clamp
      capacitance measurements. Elementary compound exocytotic events were
      characterized by multiple-amplitude on-steps in synaptopHluorin fluorescence and
      in membrane capacitance signals. Multiple-amplitude on-steps appeared either as a
      relatively large upward step, indicating that vesicles were fused with each other
      prior to fusion of the vesicle membrane with the plasma membrane (multivesicular
      exocytosis), or as a time-dependent stepwise signal increase, indicating
      sequential fusion of two or more vesicles with the plasma membrane (sequential
      exocytosis). In the majority of membrane capacitance recordings (>90%), multiple
      amplitude on-steps terminated as multiple-amplitude off-steps. These complex
      amplitude events were repetitive, indicating that transient fusion pore openings
      reflect repetitive interactions of a single vesicle or vesicles in a cluster with
      the plasma membrane. Out of many mechanisms, these interactions may enable the
      diffusion of fusion proteins from the plasma membrane to the membrane of the
      primary fused vesicles, consequently enabling vesicle-to-vesicle fusion. The
      incidence of compound exocytotic events increased by 33% after stimulation, which
      is consistent with the enhanced efficiency of hormone secretion after the
      stimulus.

PMID- 19161378
TI  - The functions of Munc18-1 in regulated exocytosis.
AB  - The activation of regulated exocytosis occurs by a rise in cytosolic Ca(2+)
      concentration. Synaptotagmins act as the Ca(2+) sensors, whereas the machinery
      that allows fusion of secretory vesicles with the plasma membrane consists of the
      soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)
      proteins, including syntaxin 1, SNAP-25, and VAMP. Within the pathway leading to
      exocytosis, there is an essential requirement for a member of the conserved
      Sec1/Munc18 (SM) protein family, which in neurotransmitter and neurohormone
      release in mammalian cells is Munc18-1. The exact role of Munc18-1 and the steps
      within exocytosis in which it acts have been intensively investigated. Current
      evidence suggests that Munc18-1 acts via distinct modes of interactions with
      syntaxin 1 and the other SNARE proteins and influences all of the steps leading
      to exocytosis, including vesicle recruitment, tethering, docking, priming, and
      membrane fusion.

PMID- 19161379
TI  - Voltage-gated potassium channel as a facilitator of exocytosis.
AB  - Voltage-gated ion channels are well characterized for their function in
      excitability signals. Accumulating studies, however, have established an ion
      independent function for the major classes of ion channels in cellular signaling.
      During the last few years we established a novel role for Kv2.1, a voltage-gated
      potassium (Kv) channel, classically known for its role of repolarizing the
      membrane potential, in facilitation of exocytosis. Kv2.1 induces facilitation of
      depolarization-induced release through its direct interaction with syntaxin, a
      protein component of the exocytotic machinery, independently of the potassium ion
      flow through the channel's pore. Here, we review our recent studies, further
      characterize the phenomena (using chromaffin cells and carbon fiber amperometry),
      and suggest plausible mechanisms that can underlie this facilitation of release.

PMID- 19161380
TI  - SNAP-25 in neuropsychiatric disorders.
AB  - SNAP-25 (synaptosomal-associated protein of 25 kDa) is a plasma membrane protein
      that, together with syntaxin and the synaptic vesicle protein VAMP/synaptobrevin,
      forms the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor) docking complex for regulated exocytosis. SNAP-25 also modulates
      different voltage-gated calcium channels, representing therefore a
      multifunctional protein that plays essential roles in neurotransmitter release at
      different steps. Recent genetic studies of human populations and of some mouse
      models implicate alterations in SNAP-25 gene structure, expression, and/or
      function in contributing directly to these distinct neuropsychiatric and
      neurological disorders.

PMID- 19161381
TI  - Exocytosis, mediatophore, and vesicular Ca2+/H+ antiport in rapid
      neurotransmission.
AB  - In rapid synapses, neurotransmitter quanta are emitted in less than 100 mus,
      often at a high frequency. Using fast cryofixation of synapses, we found a very
      brief (2-3 ms) change affecting intramembrane particles in presynaptic membrane.
      Vesicle openings also occurred but after a significant delay. The particle change
      is most probably linked to mediatophore, a proteolipid of 220 kDa. Mediatophore
      aggregates were demonstrated in active zones of the presynaptic membrane.
      Reconstituted in liposomes, Xenopus oocytes, and neuroblastoma cells,
      mediatophore releases acetylcholine in a Ca(2+)-dependent and quantal manner,
      mimicking physiological release. In restricted presynaptic "nanodomains," Ca(2+)
      concentration explosively reaches a high level and then vanishes with a time
      constant of 300-400 micros. Among the processes contributing to the fast phase of
      Ca(2+) buffering, a vesicular Ca(2+)/H(+) antiport plays a major role. Energized
      by the Vesicular-ATPase-dependent proton gradient, the antiport has a low
      affinity for Ca(2+). We inactivated the Ca(2+)/H(+) antiport using bafilomycin
      A1, which annihilates the proton gradient. As a result, the postsynaptic
      potential was increased in duration for about 3 ms, an effect caused by
      persistence of transmitter release. A similar change was obtained by replacing
      extracellular Ca(2+) by strontium, which inhibits the antiport. The antiport
      function, therefore, is to abbreviate the presynaptic Ca(2+) signal, making
      transmitter release briefer. This allows transmission to operate at high
      frequency. Following a brief period of stimulation, calcium transiently
      accumulates in synaptic vesicles where it is exchanged against transmitter.
      Calcium is subsequently cleared from the terminal, most probably by exocytosis.

PMID- 19161382
TI  - Single molecule probing of SNARE proteins by atomic force microscopy.
AB  - Atomic force microscopy (AFM) in force spectroscopy mode has recently emerged as
      a technique of choice for studying mechanical interactions between the proteins
      of the core soluble N-ethylmaleimide-sensitive fusion protein attachment protein
      attachment protein receptor (SNARE) complex. In these experiments, the rupture
      force, extension, spontaneous dissociation time, and interaction energy for SNARE
      protein-protein interactions can be obtained at the single molecule level. These
      measurements, which are complementary to results and conclusions drawn from other
      techniques, improve our understanding of the role of the SNARE complex in
      exocytosis.

PMID- 19161383
TI  - Identifying critical components of native Ca2+-triggered membrane fusion.
      Integrating studies of proteins and lipids.
AB  - Ca(2+)-triggered membrane fusion is the defining step of exocytosis. Despite
      realization that the fusion machinery must include lipids and proteins working in
      concert, only of late has work in the field focused more equally on both these
      components. Here we use isolated sea urchin egg cortical vesicles (CV), a stage
      specific preparation of Ca(2+)-sensitive release-ready vesicles that enables the
      tight coupling of molecular and functional analyses necessary to dissect
      molecular mechanisms. The stalk-pore hypothesis proposes that bilayer merger
      proceeds rapidly via transient, high-negative curvature, intermediate membrane
      structures. Consistent with this, cholesterol, a major component of the CV
      membrane, contributes to a critical local negative curvature that supports
      formation of lipidic fusion intermediates. Following cholesterol depletion,
      structurally dissimilar lipids having intrinsic negative curvature greater than
      or equal to cholesterol recover the ability of CV to fuse but do not recover
      fusion efficiency (Ca(2+) sensitivity and kinetics). Conversely, cholesterol- and
      sphingomyelin-enriched microdomains regulate the efficiency of the fusion
      mechanism, presumably by contributing spatial and functional organization of
      other critical lipids and proteins at the fusion site. Critical proteins are
      thought to participate in Ca(2+) sensing, initiating membrane deformations, and
      facilitating fusion pore expansion. Capitalizing on a novel effect of the thiol
      reactive reagent iodoacetamide (IA), potentiation of the Ca(2+) sensitivity and
      kinetics, a fluorescently tagged IA has been used to enhance fusion efficiency
      and simultaneously label the proteins involved. Isolation of cholesterol-enriched
      CV membrane fractions, using density gradient centrifugation, is being used to
      narrow the list of protein candidates potentially critical to the mechanism of
      fast Ca(2+)-triggered membrane fusion.

PMID- 19161384
TI  - The fusion pore and vesicle cargo discharge modulation.
AB  - Exocytosis, the merger of the vesicle membrane with the plasma membrane, is
      thought to mediate the release of hormones and neurotransmitters from secretory
      vesicles. The work of Bernard Katz and colleagues decades ago considered that
      vesicle cargo discharge initially requires the delivery of secretory vesicles to
      the plasma membrane where vesicles dock and are primed for fusion with the plasma
      membrane. Then, upon stimulation, the vesicle and the plasma membranes fuse to
      form a transient fusion pore through which cargo molecules diffuse out of the
      vesicle lumen into the extracellular space. Katz and colleagues considered this
      process to occur in an all-or-none fashion. However, recent studies show that
      this may not be so simple. The aim of this overview is to highlight the novel
      findings that indicate that fusion pores are subject to regulations, which affect
      the release competence of a single vesicle. Here we discuss the elementary
      properties of spontaneous and stimulated peptidergic vesicle discharge, which
      appears to be modulated, at least in pituitary lactotrophs, by fusion pore
      conductance (pore diameter) and fusion pore gating (kinetics).

PMID- 19161385
TI  - SNAP-25 and gene-targeted mouse mutants.
AB  - The evolutionary conserved soluble N-ethylmaleimide-sensitive factor attachment
      protein receptor (SNARE) fusion machinery is the operational unit in the release
      of neurotransmitters and hormones from excitable cells. The SNARE core complex
      consists of three proteins named SNAP-25 (synaptosomal-associated protein of 25
      kD), syntaxin 1, and VAMP (vesicle-associated membrane protein)/synaptobrevin.
      Syntaxin 1 is, together with SNAP-25, localized to the plasma membrane, whereas
      VAMP/synaptobrevin is a component of secretory vesicles. In concert with the
      SNAREs, accessory factors govern the docking and priming of secretory vesicles
      prior to trans-SNARE complex formation and ultimately Ca(2+)-triggered fusion
      pore opening at the plasma membrane. The synaptic SNAP-25 protein exists as two
      closely related protein variants, named SNAP-25a and SNAP-25b. SNAP-25a and SNAP
      25b are both encoded from a single copy gene and generated by obligate
      alternative splicing between two similar exon 5 sequences. Exon 5 spans a region
      of SNAP-25 that is subject to posttranslational palmitoylation and implicated in
      membrane anchoring of this cytosolic protein. The alternative splicing is
      strictly developmentally and neuroanatomically regulated, but the biological
      relevance of the distinct expression of these two similar protein variants is
      still a question of debate. However, recent findings in gene-targeted mouse
      mutants have started to unravel the importance that physiological levels of total
      SNAP-25 protein are present and, importantly, that this is accompanied by a
      balanced expression of SNAP-25a and SNAP-25b.

PMID- 19161386
TI  - Rescuing the subprime meltdown in insulin exocytosis in diabetes.
AB  - Neuroendocrine pancreatic islet beta-cells secrete the hormone insulin in
      response to glucose stimulation and adapt efficiently to increased demand by
      peripheral tissues to maintain glucose homeostasis. Insulin is packed within
      dense-core granules, which traffic and dock onto the plasma membrane whereby a
      Ca(2+) stimulus evokes exocytosis by soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor (SNARE), complex-mediated, membrane fusion. Recent
      studies have unveiled postdocking steps mediated by "priming" factors that
      influence SNARE complex assembly to confer fusion readiness to the docked
      granules. This review will summarize recent insights into the priming role for
      Munc13 in the exocytosis of insulin granules. We present evidence for the
      interaction of Munc13-1 with exocytotic substrates involved in cAMP-mediated
      potentiation of insulin release, the latter we show to mediate enhanced granule
      to-granule fusion events underlying compound exocytosis. We thus also further
      review the current understanding of granule-to-granule fusion. As agents acting
      on cAMP signaling are clinically used to augment insulin release in diabetes,
      this better understanding of priming steps may reveal additional novel
      therapeutic strategies to increase the capacity for insulin release to improve
      the treatment of diabetes.

PMID- 19161387
TI  - Phosphatidylinositol-4,5-bisphosphate-dependent facilitation of the ATP-dependent
      secretory activity in mouse pituitary cells.
AB  - Phosphatidylinositol-4, 5-bisphosphate [PI(4,5)P(2)] has been implicated in the
      priming of large dense-core vesicles in many secretory cells; however, its role
      in the Ca(2+)-dependent secretory activity in pituitary cells remains elusive. We
      assessed the effect of elevated intracellular PI(4,5)P(2) on the kinetics of
      Ca(2+)-dependent exocytosis, using a whole-cell patch-clamp technique in wild
      type mouse melanotrophs from fresh pituitary tissue slices. We found that 1
      micromol/L PI(4,5)P(2) significantly increased Ca(2+)-dependent exocytosis of
      vesicles that need to go through ATP-dependent reactions; however, the exocytosis
      of release-ready vesicles (ATP-independent release) and voltage-activated Ca(2+)
      currents remained unaffected. We suggest that PI(4,5)P(2) increases the size of
      the readily releasable vesicle pool by regulating the effectiveness of vesicular
      mobilization and fusion in an ATP-dependent manner.

PMID- 19161388
TI  - Multiple roles of Gi/o protein-coupled receptors in control of action potential
      secretion coupling in pituitary lactotrophs.
AB  - G(i/o) protein-coupled receptors, signaling through G protein-dependent and
      protein-independent pathways, have prominent effects on secretion by modulating
      calcium signaling and regulating the size of the releasable secretory pool, the
      rates of exocytosis and endocytosis, and de novo synthesis. Pituitary cells fire
      action potentials spontaneously, and the associated calcium influx is sufficient
      to maintain prolactin (PRL) release but not gonadotropin release at high and
      steady levels for many hours. Such secretion, termed intrinsic, spontaneous, or
      basal, reflects fusion of secretory vesicles triggered by the cell type-specific
      pattern of action potentials. In lactotrophs, activation of endothelin ET(A) and
      dopamine D(2) receptors causes inhibition of spontaneous electrical activity and
      basal adenylyl cyclase activity accompanied with inhibition of basal PRL release.
      Agonist-induced inhibition of cAMP production and firing of action potentials is
      abolished in cells with blocked pertussis toxin (PTX)-sensitive G(i/o) signaling
      pathway. However, agonist-induced inhibition of PRL release is only partially
      relieved in such treated cells, indicating that both receptors also inhibit
      exocytosis downstream of cAMP/calcium signaling. The PTX-insensitive step in
      agonist-induced inhibition of PRL release is not affected by inhibition of
      phosphoinositide 3-kinase and glycogen synthase kinase-3 but is partially rescued
      by downregulation of the G(z)alpha expression. Thus, ET(A) and D(2) receptors
      inhibit basal PRL release not only by blocking electrical activity but also by
      desensitizing calcium-secretion coupling.

PMID- 19161389
TI  - Exocytotic properties of human pancreatic beta-cells.
AB  - Pancreatic beta-cells secrete insulin in response to elevated blood glucose via
      Ca(2+)-dependent fusion of secretory granules with the plasma membrane (regulated
      exocytosis). While exocytosis has been extensively investigated in rodent beta
      cells, studies on human beta-cells are scarce. We have characterized the
      exocytotic properties of human beta-cells by insulin release measurements, carbon
      fiber amperometry, and capacitance measurements using the patch-clamp technique.
      Voltage-clamp depolarizations evoked capacitance increases in single beta-cells
      in a time- and voltage-dependent manner. The capacitance responses as well as
      insulin release from intact islets were strongly amplified by elevation of
      intracellular cAMP levels. Exocytosis was more dependent on Ca(2+) influx through
      P/Q-type than L-type Ca(2+) channels, reflecting the relative contribution of
      these channels to the total Ca(2+) current. Exocytosis (as monitored by
      capacitance or amperometric measurements) decreased during repetitive stimulation
      as a result of inactivation of Ca(2+) channels as well as depletion of a readily
      releasable pool of granules. These results reveal both similarities and
      differences between human and rodent beta-cells.

PMID- 19161390
TI  - Expression of dense-core vesicles and of their exocytosis are governed by the
      repressive transcription factor NRSF/REST.
AB  - The mechanism by which neurons and neurosecretory cells govern the expression and
      the exocytic discharge of their clear and dense-core vesicles had remained
      unclear until recently when studies in the neurosecretory cell model PC12
      revealed these processes to be orchestrated by the transcriptional repressor
      neuron restrictive silencer factor (NRSF)/repressor element-1 silencing
      transcription factor (REST). In wild-type PC12 fully competent for
      neurosecretion, NRSF/REST is low. The genes of the proteins involved in
      neurosecretion [from the secretory to vesicle membrane and plasma membrane
      proteins, including the soluble N-ethylmaleimide-sensitive factor attachment
      protein receptors (SNAREs) of exocytosis] were all repressed by increases of
      NRSF/REST expression to various extents when the increase was only a fewfold but
      were completely or almost completely repressed when the increase was large, as in
      spontaneously defective PC12 clones. In the first case the dense-core vesicles
      were still competent for exocytosis but were smaller and less dense than in wild
      type cells; in the second they were no longer visible but did reappear when the
      repression was attenuated by transfection of a dominant-negative construct of
      NRSF/REST combined with a secretory chromogranin or strengthened by treatment
      with a blocker of NRSF/REST-associated enzymes, the histone deacetylases.

PMID- 19161391
TI  - The Coffin-Lowry syndrome-associated protein RSK2 controls neuroendocrine
      secretion through the regulation of phospholipase D1 at the exocytotic sites.
AB  - Together with the soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor (SNARE) proteins, fusogenic cone-shaped lipids, such as phosphatidic
      acid (PA), have been recently shown to be important actors in membrane fusion
      during exocytosis. Phospholipase D (PLD) appears to be the main provider of PA at
      the exocytotic site in neuroendocrine cells. We show here that ribosomal S6
      kinase 2 (RSK2) stimulates PLD activity through the phosphorylation of Thr147 in
      the PLD1 amino-terminal Phox-homology domain. In PC12 cells, depletion of RSK2
      dramatically prevents PA synthesis at exocytotic sites and inhibits hormone
      release. Expression of PLD1 phosphomimetic mutants fully restores secretion in
      cells depleted of RSK2, suggesting that RSK2 is a critical upstream signaling
      element in the activation of PLD1 to produce the lipids required for exocytosis.

PMID- 19161392
TI  - Calcium-regulated exocytosis in neuroendocrine cells: intersectin-1L stimulates
      actin polymerization and exocytosis by activating Cdc42.
AB  - Actin cytoskeleton remodeling is a critical step of regulated exocytosis in many
      secretory cell types, including neuroendocrine cells. While the classical model
      considers the cortical actin network as a physical barrier preventing the
      uncontrolled recruitment of secretory granules to the plasma membrane docking
      sites, recent evidence supports the idea that actin polymerization also plays a
      more active role in the late stages of exocytosis. However, the molecular
      machinery underlying this positive function of actin in the course of exocytosis
      remains largely unknown. Here, we propose that the neuronal guanine nucleotide
      exchange factor, intersectin-1L, activates the GTPase Cdc42, which in turn
      provides de novo actin filaments that are important for calcium-regulated
      exocytosis in PC12 cells.

PMID- 19161393
TI  - A neurotoxic secretory phospholipase A2 induces apoptosis in motoneuron-like
      cells.
AB  - Ammodytoxin A (AtxA) is a presynaptically neurotoxic secretory phospholipase A(2)
      from snake venom. The aim of this study was to investigate the mechanism of its
      cytotoxicity expressed against mouse motoneuronal NSC34 cells. AtxA displayed a
      potent dose- and time-dependent cytotoxicity that was associated with apoptosis
      and not necrosis, as revealed by a reduction of mitochondrial membrane potential,
      activation of caspase-3, and by the absence of propidium iodide staining. The
      cytotoxic- and apoptosis-inducing effects of AtxA were specific for the
      motoneuronal cells; human embryonic kidney (HEK293) and mouse myoblast (C2C12)
      cells were shown to be resistant to the toxin.

PMID- 19161394
TI  - Treatment of non-alcoholic fatty liver disease in children: swim at your own
      risk.

PMID- 19161396
TI  - Application of nonlinear optical microscopy for imaging skin.
AB  - Recent advances in the use of nonlinear optical microscopy (NLOM) in skin
      microscopy are presented. Nonresonant spectroscopies including second harmonic
      generation, coherent anti-Stokes Raman and two-photon absorption are described
      and applications to problems in skin biology are detailed. These nonlinear
      techniques have several advantages over traditional microscopy methods that rely
      on one-photon excitation: intrinsic 3D imaging with <1 microm spatial resolution,
      decreased photodamage to tissue samples and penetration depths up to 1,000 microm
      with the use of near-infrared lasers. Thanks to these advantages, nonlinear
      optical spectroscopy has become a powerful tool to study the physical and
      biochemical properties of the skin. Structural information can be obtained using
      the response of endogenous chemical species in the skin, such as collagen or
      lipids, indicating that optical biopsy may replace current invasive, time
      consuming traditional histology methods. Insertion of specific probe molecules
      into the skin provides the opportunity to monitor specific biochemical processes
      such as skin transport, molecular penetration, barrier homeostasis and
      ultraviolet radiation-induced reactive oxygen species generation. While the field
      is quite new, it seems likely that the use of NLOM to probe structure and
      biochemistry of live skin samples will only continue to grow.

PMID- 19161397
TI  - Effect of UVR on lake water and macrophyte leachates in shallow Andean-Patagonian
      lakes: bacterial response to changes in optical features.
AB  - The aim of this study was to identify bacterial responses in two shallow lakes
      from Patagonia to UV-irradiated dissolved organic matter (DOM) coming from
      different sources. We carried out laboratory experiments in which natural lake
      water and Potamogeton linguatus leachates were irradiated (UVA-340 fluorescent
      tubes Q-Panel) or kept in darkness. Natural bacterial assemblages were then
      incubated in four treatments: natural lake water, irradiated lake water,
      macrophyte leachate and irradiated macrophyte leachate. We estimated bacterial
      abundance, composition and activity, and changes in the optical features of DOM.
      Our results showed that the addition of leachates caused an increase in the DOM
      mean molecular size. After UV exposure, a high bacterial activity was observed in
      lake water treatments. On the contrary, carbon uptake by bacteria was reduced in
      the irradiated leachate treatment. The degree of aromatization in the leachate
      treatments increased and thus may contribute to a dissolved carbon less available
      for bacterial activity. Regarding the bacteria assemblage we observed that beta
      Proteobacteria outcompete the other groups in the leachate treatments, this group
      being more efficient at utilizing the high molecular weight DOM. These results
      highlight the importance of UVR interacting with different DOM sources in
      bacteria responses of shallow lakes.

PMID- 19161398
TI  - Monte carlo model of stricture formation in photodynamic therapy of normal pig
      esophagus.
AB  - Photodynamic therapy (PDT) is FDA-approved for use in patients with Barrett's
      esophagus using porfimer sodium (2 mg per kg) and a recommended light dose of 130
      J cm(-1) for high grade dysplasia. Despite uniform drug and light doses, the
      clinical outcome of PDT is variable. A significant number of PDT cases result in
      esophageal strictures, a side effect related to excessive energy absorption. The
      purpose of this project was to model esophageal stricture formation with a Monte
      Carlo simulation. An original multilayer Monte Carlo computer simulation was
      developed for esophageal PDT. Optical absorption and scattering coefficients were
      derived for mucosal and muscle layers of normal porcine esophagus. Porfimer
      sodium was added to each layer by increasing the absorption coefficient by the
      appropriate amount. A threshold-absorbed light dose was assumed to be required
      for stricture formation and ablation. The simulation predicted irreversible
      damage to the mucosa with a 160 J cm(-1) light dose and damage to the muscle
      layer with an additional 160 J cm(-1) light dose for a tissue porfimer sodium
      content of 3.5 mg kg(-1). The simulation accurately modeled photodynamic
      stricture formation in normal pig in vivo esophageal tissue. This preliminary
      work suggests that the absorbed light threshold for stricture formation may be
      between 2 and 4 J per gram of tissue.

PMID- 19161395
TI  - Gold nanorods as contrast agents for biological imaging: optical properties,
      surface conjugation and photothermal effects.
AB  - Gold nanorods (NRs) have plasmon-resonant absorption and scattering in the near
      infrared (NIR) region, making them attractive probes for in vitro and in vivo
      imaging. In the cellular environment, NRs can provide scattering contrast for
      darkfield microscopy, or emit a strong two-photon luminescence due to plasmon
      enhanced two-photon absorption. NRs have also been employed in biomedical imaging
      modalities such as optical coherence tomography or photoacoustic tomography.
      Careful control over surface chemistry enhances the capacity of NRs as biological
      imaging agents by enabling cell-specific targeting, and by increasing their
      dispersion stability and circulation lifetimes. NRs can also efficiently convert
      optical energy into heat, and inflict localized damage to tumor cells. Laser
      induced heating of NRs can disrupt cell membrane integrity and homeostasis,
      resulting in Ca(2+) influx and the depolymerization of the intracellular actin
      network. The combination of plasmon-resonant optical properties, intense local
      photothermal effects and robust surface chemistry render gold NRs as promising
      theragnostic agents.

PMID- 19161399
TI  - Long-term UVB irradiation affects the immune functions of carp (Cyprinus carpio)
      and rainbow trout (Oncorhynchus mykiss).
AB  - The effects of long-term, low-dose ultraviolet B (UVB) radiation on immune
      functions of two fish species representing different taxonomic groups, carp
      (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss), were assessed in this
      study. The fish were exposed to 7, 20 or 60 mJ cm(-2) UVB three times per week,
      for 6 weeks. In carp, UVB exposure affected the respiratory burst activity of
      blood and head kidney phagocytes, differential blood leukocyte counts and blood
      chemistry. Phytohemagglutinin (PHA)-stimulated in vitro proliferation responses
      of blood and head kidney lymphocytes, however, remained unchanged. Rainbow trout
      tolerated the irradiations with fewer alterations, but significant changes were
      detected in blood chemistry and hematocrits of the irradiated fish. These results
      indicate that long-term exposure to low doses of UVB induces immunomodulation in
      fish, and that there are species-specific differences in sensitivity to
      irradiation.

PMID- 19161400
TI  - Nanoscale hydroxyl radical generation from multiphoton ionization of tryptophan.
AB  - Exposure of solutions containing both tryptophan and hydrogen peroxide to a
      pulsed ( approximately 180 fs) laser beam at 750 nm induces luminescence
      characteristic of 5-hydroxytryptophan. The results indicate that 3-photon
      excitation of tryptophan results in photoionization within the focal volume of
      the laser beam. The resulting hydrated electron is scavenged by hydrogen peroxide
      to produce the hydroxyl radical. The latter subsequently reacts with tryptophan
      to form 5-hydroxytryptophan. The involvement of hydroxyl radicals is confirmed by
      the use of ethanol and nitrous oxide as scavengers and their effects on the
      fluorescence yield in this system. It is postulated that such multiphoton
      ionization of tryptophanyl residues in cellular proteins may contribute to the
      photodamage observed during imaging of cells and tissues using multiphoton
      microscopy.

PMID- 19161401
TI  - Fluorescence detection of the ornamental fish Cardinal Tetra (Paracheirodon
      axelrodi).
AB  - The fluorescence spectra of the tropical fish, Cardinal Tetra (Paracheirodon
      axelrodi), originating in the Amazon region of Brazil, were determined. These
      spectra were then treated using factor analysis, generating two contributing
      spectra and separating out the noise. Time-resolved fluorescence results
      indicated that the fluorescent system in the epidermis undergoes excited state
      reaction. Excited state proton transfer is suggested as being present. Both
      intentionally stressed and nonstressed individuals were used and some small
      differences were noted in the contributions of the two calculated contributing
      spectra to the experimental spectra, presumably as a function of stress. The
      results are compared with those obtained by the standard determination of
      cortisol level using the whole body extraction method and it is suggested that
      the method could be tested as an improved, nondestructive way to determine stress
      in this species, which is a necessary step in the development of "best management
      practices" of methods for storage and transport of the fish.

PMID- 19161402
TI  - New results on the photochemistry of biopterin and neopterin in aqueous solution.
AB  - New photochemical studies of the reactivity of biopterin (BPT) and neopterin
      (NPT) in acidic (pH = 5.5) and alkaline (pH = 10.5) aqueous solutions at 350 nm
      and room temperature were performed. The photochemical properties of BPT are of
      particular interest because the photolysis of this compound takes place in the
      white skin patches of patients affected by vitiligo. The photochemical reactions
      were followed by UV/VIS spectrophotometry, HPLC, electrochemical measurement of
      dissolved O(2) and enzymatic methods for hydrogen peroxide (H(2)O(2)) and
      superoxide anion (O(2)(-)) determinations. When BPT or NPT are exposed to UVA
      radiation, a red intermediate, very likely 6-formyl-5,8-dihydropterin, is
      generated in an O(2)-independent process. That product is rapidly oxidized on
      admission of O(2) to yield 6-formylpterin and H(2)O(2). When the photolysis takes
      place in aerobic conditions, no additional pathways exist. On the other hand, in
      the absence of O(2), the intermediate generated is not stable and leads to the
      formation of many products. O(2)(-) is also generated during photo-oxidation of
      BPT and NPT. The quantum yields of reactant consumption depends on the O(2)
      concentration: the higher the O(2) concentration, the lower the quantum yields.
      This behavior is discussed in connection with the excited state of the pterins.

PMID- 19161403
TI  - The effect of chronic exposure to artificial UVB radiation on the survival and
      reproduction of Daphnia magna across two generations.
AB  - We examined the effects of daily (chronic) exposure to artificial UVB radiation
      on the survival and reproduction of Daphnia magna over two generations. Control
      and experimental animals in each generation (parental and F1) were exposed to 16
      h of UVA radiation and photosynthetically active radiation daily. In addition,
      experimental animals were exposed to 6 h of UVB during the middle of the light
      period. Survival and reproduction were followed for 12 days for each individual.
      Survival and production of F1 were significantly lower in the UVB exposed
      parental generation Daphnia than in controls. F1 exposure to UVB significantly
      decreased F1 survival and reproduction. Reproduction was lowest in UVB exposed F1
      animals whose parents were also exposed to UVB. Adverse effects of UVB on
      offspring production may be magnified in successive generations suggesting that
      short-term experiments could underestimate the impact of increased UVB exposure
      on populations.

PMID- 19161404
TI  - Patterns of persistent DNA damage associated with sun exposure and the
      glutathione S-transferase M1 genotype in melanoma patients.
AB  - Solar radiation can lead to changes affecting DNA metabolism resulting in loss of
      DNA integrity. Skin specimens obtained from melanoma patients treated at the
      Memorial Sloan-Kettering Cancer Center were used to study patterns of DNA
      fragmentation using the comet assay and levels of deletions in mitochondrial DNA
      (mtDNA) using real-time PCR. Skin specimens were classified according to the
      glutathione S-transferase M1 (GSTM1) genotype (either wild type [WT] or null) and
      patient sunburn history. GSTM1 null individuals with a sunburn history showed
      increased levels of both DNA fragmentation by comet assays and mtDNA deletions
      relative to GSTM1 WT patients with little or no sunburn history. Microarray
      analyses identified a number of genes whose expression was upregulated >or=5-fold
      in cells from GSTM1-null patients or from those reporting histories of sunburn.
      These genes encoded small molecule transporters, various growth factor/chemokine
      receptors, transcription factors and tumor suppressors. Of 17 genes directly
      involved in DNA repair, three DNA ligases were highly upregulated while the RAD23
      UV excision repair gene and the Growth Arrest and DNA Damage gene (GADD45) were
      downregulated. These findings support the idea that exposure to solar radiation
      early in life may induce long-term cellular changes that lead to persistent DNA
      damage and altered patterns of gene expression.

PMID- 19161405
TI  - Quenching of singlet oxygen by a carotenoid-cyclodextrin complex: the importance
      of aggregate formation.
AB  - The Girard's reagent P derivative of canthaxanthin ((GRP)(2)-canthaxanthin), a
      dicationic carotenoid, forms a highly water-dispersible complex with (2
      hydroxypropyl)-gamma-cyclodextrin. The UV-visible light spectrum of the complex
      is consistent with some degree of aggregation, but the spectrum is independent of
      concentration from 7.5 to 750 mum. Stern-Vomer plots for singlet-oxygen quenching
      by the complex are linear over a concentration range of 0-20 mum. In the presence
      of 1 mm (2-hydroxypropyl)-gamma-cyclodextrin, the singlet-oxygen quenching
      constant for the complex is 7.9 +/- 0.9 x 10(8) m(-1)s(-1). This is about an
      order of magnitude lower than the singlet-oxygen quenching constants for (GRP)(2)
      canthaxanthin in various organic solvents. The properties of the complex are also
      compared with the properties of (GRP)(2)-canthaxanthin solubilized in neat water
      and in water containing various detergents. The singlet-oxygen quenching constant
      for (GRP)(2)-canthaxanthin in micelles depends strongly on the specific detergent
      used, varying from 9.4 x 10(8) m(-1)s(-1) for hexadecyltrimethylammonium bromide
      (CTAB) to 1.24 +/- 0.4 x 10(10) m(-1)s(-1) for sodium dodecyl sulfate. The small
      quenching constant in CTAB micelles correlates with spectroscopic evidence for
      aggregation of the (GRP)(2)-canthaxanthin in this detergent.

PMID- 19161406
TI  - Photocycles of channelrhodopsin-2.
AB  - Recent developments have used light-activated channels or transporters to
      modulate neuronal activity. One such genetically-encoded modulator of activity,
      channelrhodopsin-2 (ChR2), depolarizes neurons in response to blue light. In this
      work, we first conducted electrophysiological studies of the photokinetics of
      hippocampal cells expressing ChR2, for various light stimulations. These and
      other experimental results were then used for systematic investigation of the
      previously proposed three-state and four-state models of the ChR2 photocycle. We
      show the limitations of the previously suggested three-state models and identify
      a four-state model that accurately follows the ChR2 photocurrents. We find that
      ChR2 currents decay biexponentially, a fact that can be explained by the four
      state model. The model is composed of two closed (C1 and C2) and two open (O1 and
      O2) states, and our simulation results suggest that they might represent the dark
      adapted (C1-O1) and light-adapted (C2-O2) branches. The crucial insight provided
      by the analysis of the new model is that it reveals an adaptation mechanism of
      the ChR2 molecule. Hence very simple organisms expressing ChR2 can use this form
      of light adaptation.

PMID- 19161407
TI  - Sunlight-induced DNA damage in marine micro-organisms collected along a
      latitudinal gradient from 70 degrees N to 68 degrees S.
AB  - We examined ultraviolet radiation (UVR)-induced DNA damage in marine micro
      organisms collected from surface seawater along a latitudinal transect in the
      Central Pacific Ocean from 70 degrees N to 68 degrees S. Samples were collected
      predawn and incubated under ambient UVR in transparent incubators at in situ
      temperatures until late afternoon at which time they were filtered into primarily
      bacterioplankton and eukaryotic fractions. Cyclobutane pyrimidine dimers (CPDs)
      and (6-4) photoproducts [(6-4)PDs] were quantified in DNA extracts using
      radioimmunoassays. UVB was lowest in the polar regions and highest near the
      equator and correlations between UVB and DNA damage were observed. The eukaryotic
      fraction showed significant CPDs across the entire transect; (6-4)PDs were
      detected only in the tropics. The bacterial fraction showed no accumulation of (6
      4)PDs at any latitude, although residual (6-4)PDs were observed. Bacterial cell
      volumes were greatest in the sub-Arctic and northern temperate latitudes and
      lower in the tropics and southern hemisphere, a unique observation that parallels
      Bergmann's rule. A strong negative correlation was observed between cell volume
      and CPDs. The environmental impact of solar UVR on marine micro-organisms in the
      open ocean is complex and our results suggest that several factors such as DNA
      repair, cell size, temperature, salinity, nutrients and species composition are
      important in determining relative sensitivity.

PMID- 19161409
TI  - Increased expression of TRPV1 channel in intrinsically aged and photoaged human
      skin in vivo.
AB  - Transient receptor potential vanilloid type 1 (TRPV1) is activated by various
      stimuli including capsaicin, heat and acid. While TRPV1 has been localized in the
      epidermis, little is known about the physiological role of TRPV1 in the skin,
      especially in skin ageing. In this study, we investigated the effect of acute UV
      irradiation on TRPV1 expression in human skin and the changes in TRPV1 mRNA and
      protein in intrinsic ageing and photoageing using human sun-protected (upper
      inner arm) and sun-exposed (forearm) skin of young and elderly subjects. Western
      blot analysis of UV-irradiated young buttock skin revealed that the expression of
      TRPV1 protein was increased at 24 h (2.3-fold) and 48 h (2.4-fold) after UV
      irradiation. Real-time PCR analysis also showed that the mRNA level of TRPV1 was
      augmented by 2.4-fold at 4 h after UV irradiation. TRPV1 protein was expressed at
      higher levels by 2.6-fold in the sun-protected skin of the elderly subjects than
      in that of young people according to western blotting, real-time PCR analysis and
      immunohistochemical staining. In addition, the photoaged skin of elderly showed
      increased expression of TRPV1 mRNA and protein compared with that of the sun
      protected skin of the same individuals. Also, we found increased expression of
      TRPV1 in nerve fibres of elderly persons using double staining of TRPV1 and nerve
      fibres. Based on the above results, our data suggest that the expression of TRPV1
      is affected by both the intrinsic ageing and photoageing processes.

PMID- 19161411
TI  - New paradigms in inflammation: where to next?

PMID- 19161412
TI  - The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress.
AB  - The interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily was first
      defined in 1998 as a family of proteins that contain the Toll-IL-1 receptor
      domain. At that time, there were a number of orphan receptors in the IL-1R
      branch, and the TLRs had yet to be shown to be key innate immune receptors that
      sense microbial products. We now know a great deal more about this superfamily,
      with the description of novel IL-1 family members such as IL-1F6 signaling via IL
      1Rrp2 and IL33 signaling via ST2. Remarkable progress has been made in our
      understanding of the functions of the TLRs, leading to a renaissance of interest
      in innate immunity. The importance of IL-1 is also being rediscovered, with the
      observation that Nalp3 is a key regulator of caspase-1, the enzyme that processes
      pro-IL-1beta into the mature cytokine. This area has therefore proved very
      fruitful in terms of improving our knowledge of the molecular basis for innate
      immunity and inflammation, and we can anticipate further discoveries in the
      coming years.

PMID- 19161413
TI  - Interleukin-2 in the development and control of inflammatory disease.
AB  - Interleukin-2 (IL-2) has multiple, sometimes opposing, functions during an
      inflammatory response. It is a potent inducer of T-cell proliferation and T
      helper 1 (Th1) and Th2 effector T-cell differentiation and provides T cells with
      a long-lasting competitive advantage resulting in the optimal survival and
      function of memory cells. In a regulatory role, IL-2 is important for the
      development, survival, and function of regulatory T cells, it enhances Fas
      mediated activation-induced cell death, and it inhibits the development of
      inflammatory Th17 cells. Thus, in its dual and contrasting functions, IL-2
      contributes to both the induction and the termination of inflammatory immune
      responses.

PMID- 19161414
TI  - Inborn errors of interferon (IFN)-mediated immunity in humans: insights into the
      respective roles of IFN-alpha/beta, IFN-gamma, and IFN-lambda in host defense.
AB  - Interferon (IFN) was originally identified as a substance 'interfering' with
      viral replication in vitro. The first IFNs to be identified were classified as
      type I IFNs (IFN-alpha/beta and related molecules), two other types have since
      been identified: type II IFN (IFN-gamma) and type III IFNs (IFN-lambda). Each IFN
      binds to one of three type-specific receptors. In the mouse model of experimental
      infections in vivo, IFN-alpha/beta are essential for immunity to most viruses
      tested, whereas IFN-gamma is important for immunity to a smaller number of
      viruses, together with bacteria, fungi, and parasites, consistent with IFN-gamma
      acting as the 'macrophage activating factor.' The precise role of IFN-lambda
      remains unclear. In recent years, inborn errors affecting the production of, or
      the response to, IFNs have been reported in human patients, shedding light onto
      the function of IFNs in natura. Disorders of IFN-gamma production, caused by
      IL12B, IL12RB1, and specific NEMO mutations, or of IFN-gamma responses, caused by
      IFNGR1, IFNGR2, and dominant STAT1 mutations, confer predisposition to
      mycobacterial disease in patients resistant to most viruses. By contrast,
      disorders of IFN-alpha/beta and IFN-lambda production, caused by UNC93B1 and TLR3
      mutations, confer predisposition to herpes simplex encephalitis (HSE) in
      otherwise healthy patients. Consistently, patients with impaired responses to IFN
      alpha/beta, IFN-gamma, and presumably IFN-lambda (carrying recessive mutations in
      STAT1), or with impaired responses to IFN-alpha/beta and impaired IFN-gamma
      production (carrying mutations in TYK2), or with impaired production of IFN
      alpha/beta, IFN-gamma, and IFN-lambda (carrying specific mutations in NEMO), are
      vulnerable to mycobacterial and viral infections, including HSE. These
      experiments of nature suggest that the three types of IFNs play at least two
      different roles in host defense. IFN-gamma is essential for anti-mycobacterial
      immunity, whereas IFN-alpha/beta and IFN-lambda are essential for anti-viral
      immunity. Future studies in humans aim to define the specific roles of IFN
      alpha/beta and IFN-lambda types and individual molecules in host defense in
      natura.

PMID- 19161416
TI  - The roles of IL-17A in inflammatory immune responses and host defense against
      pathogens.
AB  - T-helper 17 (Th17) cells are a newly discovered CD4(+) helper T-cell subset that
      produces interleukin-17A (IL-17A) and IL-17F. IL-17A plays important roles in
      allergic responses such as delayed-type hypersensitivity, contact
      hypersensitivity, and allergic airway inflammation. IL-17A promotes inflammation
      by inducing various proinflammatory cytokines and chemokines, recruiting
      neutrophils, enhancing antibody production, and activating T cells. IL-17A
      expression is also augmented in autoimmune diseases such as multiple sclerosis
      and rheumatoid arthritis. Using mouse models of these diseases, we found that IL
      17A plays a central role in their development. IL-6 is required for the
      development of Th17 cells and tumor necrosis factor functions downstream of IL
      17A during the effector phase. IL-1 is important both for developing Th17 cells
      and eliciting inflammation. Th17 cells, like Th1 and Th2 cells, are involved in
      host defense against infections, but the contribution of these Th subsets to
      defense mechanisms differs among pathogens. The roles of IL-17F remain largely
      unknown. In this review, we introduce how IL-17A/IL-17F are involved in
      inflammatory immune responses and host defense mechanisms and discuss their
      relationship with other cytokines in the development of inflammatory and
      infectious diseases.

PMID- 19161415
TI  - Regulation of interferon and Toll-like receptor signaling during macrophage
      activation by opposing feedforward and feedback inhibition mechanisms.
AB  - Activated macrophages and their inflammatory products play a key role in innate
      immunity and in pathogenesis of autoimmune/inflammatory diseases. Macrophage
      activation needs to be tightly regulated to rapidly mount responses to infectious
      challenges but to avoid toxicity associated with excessive activation. Rapid and
      potent macrophage activation is driven by cytokine-mediated feedforward loops,
      while excessive activation is prevented by feedback inhibition. Here we discuss
      feedforward mechanisms that augment macrophage responses to Toll-like receptor
      (TLR) ligands and cytokines that are mediated by signal transducer and activator
      of transcription 1 (STAT1) and induced by interferon-gamma (IFN-gamma). IFN-gamma
      also drives full macrophage activation by inactivating feedback inhibitory
      mechanisms, such as those mediated by interleukin-10 (IL-10), and STAT3. Priming
      of macrophages with IFN-gamma reprograms cellular responses to other cytokines,
      such as type I IFNs and IL-10, with a shift toward pro-inflammatory STAT1
      dominated responses. Similar but partially distinct priming effects are induced
      by other cytokines that activate STAT1, including type I IFNs and IL-27. We
      propose a model whereby opposing feedforward and feedback inhibition loops
      crossregulate each other to fine tune macrophage activation. In addition, we
      discuss how dysregulation of the balance between feedforward and feedback
      inhibitory mechanisms can contribute to the pathogenesis of autoimmune and
      inflammatory diseases, such as rheumatoid arthritis and systemic lupus
      erythematosus.

PMID- 19161418
TI  - Th17 cytokines and their emerging roles in inflammation and autoimmunity.
AB  - T-helper 17 (Th17) cells are a new lineage of CD4(+) T cells that are
      characterized by their production of interleukin-17A (IL-17A). Recent studies
      show that these cells can also express IL-17F, IL-22, and IL-21. IL-17A and IL
      17F can form a heterodimeric cytokine, which mediates biological activities, at
      least in part, through shared receptors with IL-17A and IL-17F homodimers. The
      cytokines made by Th17 cells represent three distinct gene families, highlighting
      the unique biology of these cells. Accumulating data support a role for Th17
      cells and these cytokines in inflammatory processes and in animal models of
      autoimmunity or inflammation. Emerging data in clinical trials support our
      understanding of the importance of Th17 cells in inflammatory disease. Future
      clinical studies will allow us to evaluate the role of each cytokine
      independently in contributing to human diseases with immune-mediated pathologies
      and to design optimal cytokine-targeted therapies for these diseases.

PMID- 19161417
TI  - Regulation and pro-inflammatory function of interleukin-17 family cytokines.
AB  - The interleukin-17 (IL-17) family consists of six cytokines in mammals. Among
      them, IL-17 and IL-17F are expressed by a novel subset of CD4(+) helper T cells
      and play critical function in inflammation and autoimmunity. IL-17E, also called
      IL-25, has been associated with allergic responses. Here, I summarize recent work
      by my laboratory as well as other investigators in understanding the regulation
      and function of these three cytokines. From these studies, IL-17 family cytokines
      may serve as novel targets for pharmaceutical intervention of immune and
      inflammatory diseases.

PMID- 19161419
TI  - Reconciling id, ego, and superego within interleukin-23.
AB  - The study of interleukin-23 (IL-23) over the past 8 years has led to the
      realization that cellular immunity is far more complex than previously
      appreciated, because it is controlled by additional newly identified players.
      From the analysis of seemingly straightforward cytokine regulation of autoimmune
      diseases, many limitations of the established paradigms emerged that required
      reevaluation of the 'rules' that govern the initiation and maintenance of immune
      responses. This information led to a major revision of the T-helper 1 (Th1)/Th2
      hypothesis and discovery of an unexpected link between transforming growth factor
      beta-dependent Th17 and inducible regulatory T cells. The aim of this review is
      to explore the multiple characteristics of IL-23 with respect to its 'id' in
      autoimmunity, 'ego' in T-cell help, and 'superego' in defense against mucosal
      pathogens.

PMID- 19161422
TI  - The interleukin-23 axis in intestinal inflammation.
AB  - Immune responses in the intestine are tightly regulated to ensure host protective
      immunity in the absence of immune pathology. Interleukin-23 (IL-23) has recently
      been shown to be a key player in influencing the balance between tolerance and
      immunity in the intestine. Production of IL-23 is enriched within the intestine
      and has been shown to orchestrate T-cell-dependent and T-cell-independent
      pathways of intestinal inflammation through effects on T-helper 1 (Th1) and Th17
      associated cytokines. Furthermore, IL-23 restrains regulatory T-cell responses in
      the gut, favoring inflammation. Polymorphisms in the IL-23 receptor have been
      associated with susceptibility to inflammatory bowel diseases (IBDs) in humans,
      pinpointing the IL-23 axis as a key, conserved pathway in intestinal homeostasis.
      In addition to its role in dysregulated inflammatory responses, there is also
      evidence that IL-23 and the Th17 axis mediate beneficial roles in host protective
      immunity and barrier function in the intestine. Here we discuss the dual roles of
      IL-23 in intestinal immunity and how IL-23 and downstream effector pathways may
      make novel targets for the treatment of IBD.

PMID- 19161420
TI  - Regulation of interleukin-12/interleukin-23 production and the T-helper 17
      response in humans.
AB  - Interleukin-12 (IL-12) and IL-23 share a common chain. Yet, their production in
      response to pathogens is differentially regulated, and their functions are
      distinct and often antithetic. IL-12 is involved in the induction or
      amplification of the T-helper (Th) type 1 response, whereas IL-23 has been
      associated with the generation of the Th17 response and IL-17 production.
      Mycobacterium tuberculosis and yeast zymosan induce IL-23, but in the absence of
      other stimuli, no IL-12 is induced in human dendritic cells (DCs). The
      stimulation of IL-23 by M. tuberculosis was mostly explained by the triggering of
      Toll-like receptor (TLR2) and the cytoplasmic receptor nucleotide oligomerization
      domain (NOD)-containing protein 2, whereas zymosan induces IL-23 primarily by
      stimulating the beta-glucan receptor dectin-1 alone or in combination with TLR2.
      IL-23, IL-6, transforming growth factor (TGF-beta1), and IL-1beta in supernatants
      from activated human DCs induce human naive CD4(+) T cells to produce IL-17.
      These data are consistent with various recent reports that TGF-beta is an inducer
      of IL-17 production both in human and in mouse cells. However, IL-1 is necessary
      in combination with some or all of the other cytokines to induce IL-17 production
      in human T cells. The ability of various stimuli to induce Th17 cells depends not
      only on their induction of IL-23, IL-6, and TGF-beta production in DCs but also
      on their ability to activate directly or indirectly the inflammasome and to
      induce IL-1beta.

PMID- 19161421
TI  - From interleukin-23 to T-helper 17 cells: human T-helper cell differentiation
      revisited.
AB  - Protracted inflammation leading to dysregulation of effector T-cell responses
      represents a common feature of a wide range of autoimmune diseases. The
      interleukin-12 (IL-12)/T-helper 1 (Th1) pathway was thought to be responsible for
      the pathogenesis of multiple chronic inflammatory diseases, including psoriasis,
      inflammatory bowel disease, arthritis, or multiple sclerosis, mainly through
      their production of interferon-gamma and its effects on macrophage activation and
      chemokine production. However, this initial concept of T-cell-mediated chronic
      inflammation required an adjustment with the discovery of an IL-12-related
      cytokine, designated IL-23. IL-23 was rapidly recognized for its involvement in
      the establishment of chronic inflammation and in the development of a Th cell
      subset producing IL-17, designated Th17, which is distinct from the previously
      reported Th1 and Th2 populations. This review aims to describe the
      characterization of IL-23 and its receptor, its biological activities, as well as
      its involvement in the development of human Th17 cells and autoimmunity.

PMID- 19161423
TI  - Th17 cytokines and mucosal immunity.
AB  - The T-helper 17 (Th17) lineage is a recently described subset of memory T cells
      that is characterized by its CD4(+) status and its ability to make a
      constellation of cytokines including interleukin-17A (IL-17A), IL-17F, IL-22,
      and, in humans, IL-26. Although most extensively described in the autoimmunity
      literature, there is growing evidence that the Th17 lineage plays a significant
      role in mediating host mucosal immunity to a number of pulmonary pathogens. This
      review highlights our current understanding of the role of the Th17 lineage and
      Th17 cytokines in mediating mucosal immunity to both pulmonary and
      gastrointestinal pathogens. While we have the strongest evidence that the Th17
      lineage is centrally involved in mediating the host response to Gram-negative
      extracellular pulmonary pathogens, this literature is rapidly evolving and
      demonstrates a central role for Th17 cytokines both in primary infection and in
      recall responses seen in vaccine studies. In this review, we summarize the
      current state of this literature and present possible applications of Th17
      targeted immunotherapy in the treatment and prevention of infection.

PMID- 19161424
TI  - Welcome to the neighborhood: epithelial cell-derived cytokines license innate and
      adaptive immune responses at mucosal sites.
AB  - There is compelling evidence that epithelial cells (ECs) at mucosal surfaces,
      beyond their role in creating a physical barrier, are integral components of
      innate and adaptive immunity. The capacity of these cells to license the
      functions of specific immune cell populations in the airway and gastrointestinal
      tract offers the prospect of novel therapeutic strategies to target multiple
      inflammatory diseases in which barrier immunity is dysregulated. In this review,
      we discuss the critical functions of EC-derived thymic stromal lymphopoietin
      (TSLP), interleukin-25 (IL-25), and IL-33 in the development and regulation of T
      helper 2 (Th2) cytokine-dependent immune responses. We first highlight recent
      data that have provided new insights into the factors that control expression of
      this triad of cytokines and their receptors. In addition, we review their
      proinflammatory and immunoregulatory functions in models of mucosal infection and
      inflammation. Lastly, we discuss new findings indicating that despite their
      diverse structural features and differential expression of their receptors, TSLP,
      IL-25, and IL-33 cross-regulate one another and share overlapping properties that
      influence Th2 cytokine-dependent responses at mucosal sites.

PMID- 19161425
TI  - The role of cytokines in the initiation, expansion, and control of cellular
      immunity to tuberculosis.
AB  - Tuberculosis (TB) results from an interaction between a potent immune response
      and a chronically persistent pathogen. The ability of Mycobacterium tuberculosis
      (Mtb) to induce a strong immune response while being able to resist the ability
      of the host to clear bacteria provides an excellent tool with which to
      investigate the role of specific cytokine pathways on the induction, expansion,
      and control of the effector T-cell response. In this review, the role of
      interleukin-12p40 (IL-12p40), IL-12p70, IL-23, and IL-27 in the immune response
      to Mtb are described. We show that IL-12(p40)(2) acts to mediate the activation
      of dendritic cells to become responsive to homeostatic chemokines. We also show
      that IL-12p70 is required for the optimal interferon-gamma (IFN-gamma) T-cell
      response, which is required for control of Mtb growth. IL-23 can induce IFN-gamma
      responses in the lung if IL-12 is not present, but its major role is in
      supporting the IL-17 response within the lung. Neither IL-23 nor IL-17 is
      required for early control of Mtb in the lung. IL-23 and IL-17, however, can be
      instrumental in vaccine-induced protection. Finally, IL-27 limits protective
      immunity in the lung, but it is also required for long-term survival. These
      cytokines are therefore key players in the immune response to TB.

PMID- 19161426
TI  - Interleukin-10: new perspectives on an old cytokine.
AB  - Interleukin-10 (IL-10) has long been recognized to have potent and broad-spectrum
      anti-inflammatory activity, which has been unequivocally established in various
      models of infection, inflammation, and even in cancer. However, because of the
      marginal successes of the initial clinical trials using recombinant IL-10, some
      of the interest in this cytokine as an anti-inflammatory therapeutic has
      diminished. New work showing IL-10 production from regulatory T cells and even T
      helper 1 T cells has reinvigorated the field and revealed the power of this
      cytokine to influence immune responses. Furthermore, new preclinical studies
      suggest that combination therapies, using antibodies to IL-10 along with
      chemotherapy, can be effective in treating bacterial, viral, or neoplastic
      diseases. Studies to understand IL-10 gene expression in the various cell types
      may lead to new therapeutics to enhance or inhibit IL-10 production. In this
      review, we summarize what is known about the regulation of IL-10 gene expression
      by various immune cells. We speculate on the promise that this cytokine holds to
      influence immune responses and mitigate immune pathologies.

PMID- 19161428
TI  - Regulation of immune responses by interleukin-27.
AB  - Cytokine-mediated immunity plays a crucial role in the pathogenesis of various
      diseases including autoimmunity. Recently, interleukin-27 (IL-27) was identified,
      which, along with IL-12, IL-23, and IL-35, belongs to the IL-12 cytokine family.
      These family members play roles in the regulation of T helper (Th) cell
      differentiation. IL-27 is unique in that while it induces Th1 differentiation,
      the same cytokine suppresses immune responses. In the absence of IL-27-mediated
      immunosuppression, hyper-production of various pro-inflammatory cytokines
      concomitant with severe inflammation in affected organs was observed in IL-27
      receptor alpha chain (WSX-1)-deficient mice infected with Trypanosoma cruzi.
      Experimental allergic or inflammatory responses were also enhanced in WSX-1
      deficient mice. The immunosuppressive effects of IL-27 depend on inhibition of
      the development of Th17 cells (a newly identified inflammatory T-helper
      population) and induction of IL-10 production. Moreover, administration of IL-27
      or augmentation of IL-27 signaling suppresses some diseases of autoimmune or
      allergic origin, demonstrating its potential in therapy of diseases mediated by
      inflammatory cytokines. In this review, we discuss recent studies on the role of
      IL-27 in immunity to parasitic and bacterial infections as well as in allergy and
      autoimmunity in view of its pro- and anti-inflammatory properties.

PMID- 19161427
TI  - Diversity in the contribution of interleukin-10 to T-cell-mediated immune
      regulation.
AB  - Recent progress in our understanding of mechanisms by which the immunosuppressive
      cytokine interleukin-10 (IL-10) participates in an ever-increasing diversity of T
      cell lineages to maintain immune homeostasis has broadened the framework for
      defining regulatory and effector T cells and has blurred the lines between them.
      In this review, we highlight established and emerging roles for IL-10 produced by
      distinct CD4(+) T-cell lineages that underlie its non-redundant role in curbing
      immune responses to the intestinal microbiota at steady state and its role to
      limit T-cell-driven inflammation in responses to pathogens.

PMID- 19161430
TI  - Coral mucus-associated bacteria: a possible first line of defense.
AB  - Interactions among microorganisms found in coral mucus can be either symbiotic or
      competitive. It has been hypothesized that microbial communities found on the
      surface of coral play a role in coral holobiont defense, possibly through
      production of antimicrobial substances. Selected microorganisms isolated from the
      mucus layer of a number of coral species were grown using agar-plating
      techniques. Screening for antimicrobial substances was performed using overlay
      and drop techniques, employing several indicator microorganisms. Between 25% and
      70% of cultivable mucus-associated bacteria from scleractinian corals
      demonstrated bioactivity. Higher percentages of activity were evident in mucus
      associated cultivable bacteria from massive and solitary corals, as compared with
      bacteria from branching or soft corals. Isolates related to the genera Vibrio and
      Pseudoalteromonas demonstrated high activity against both Gram-positive and Gram
      negative bacteria. Gram-positive bacteria (Bacillus, Planomicrobium) demonstrated
      lower levels of activity, primarily against other Gram-positive bacteria. In some
      cases, inhibitory effects were confined to the cell fraction, suggesting the
      involvement of a cell-bound molecule, sensitive to temperature and most likely
      proteinaceous in nature. These results demonstrate the existence of
      microorganisms with antimicrobial activity on the coral surface, possibly acting
      as a first line of defense to protect the coral host against pathogens.

PMID- 19161429
TI  - Interleukin-35: odd one out or part of the family?
AB  - Advances in cytokine biology have helped us understand the complex communication
      that takes place between antigen-presenting cells and cells of the adaptive
      immune system, such as T cells, which collectively mediate an appropriate immune
      response to a plethora of pathogens while maintaining tolerance to self-antigens.
      The interleukin-12 (IL-12) cytokine family remains one of the most important and
      includes IL-12, IL-23, IL-27, and the recently identified IL-35. All four are
      heterodimeric cytokines, composed of an alpha chain (p19, p28, or p35) and a beta
      chain (p40 or Ebi3), and signal through unique pairings of five receptor chains
      (IL-12Rbeta1, IL-12Rbeta2, IL-23R, gp130, and WSX-1). Despite the
      interrelationship between the cytokines themselves and their receptors, their
      source, activity, and kinetics of expression are quite different. Studies using
      genetically deficient mice have greatly enhanced our understanding of the biology
      of these cytokines. However, interpretation of these data has been complicated by
      the recent realization that p40(-/-), p35(-/-), and Ebi3(-/-) mice all lack more
      than one cytokine (IL-12/IL-23, IL-12/IL-35, and IL-27/IL-35, respectively). In
      this review, we compare and contrast the biology of this expanded IL-12 family
      and re-evaluate data derived from the analysis of these dual cytokine-deficient
      mice. We also discuss how the opposing characteristics of the IL-12 family
      siblings may help to promote a balanced immune response.

PMID- 19161431
TI  - Spatial heterogeneity of periphytic microbial communities in a small pesticide
      polluted river.
AB  - Spatial variability in the microbial community composition of river biofilms was
      investigated in a small river using two spatial scales: one monitored the
      upstream-downstream pesticide contamination gradient, referred to as the 'between
      section variability', and the other monitored a 100-m longitudinal transect
      (eight sampling sites per section) within each sampling section, referred to as
      the 'within-section variability'. Periphyton samples were collected in spring and
      winter on artificial substrates placed in the main channel of the river.
      Denaturing gradient gel electrophoresis (DGGE) was used to assess the prokaryotic
      and eukaryotic community richness and diversity, and HPLC pigment analysis to
      assess the global taxonomic composition of the photoautotrophic community. In
      order to try to reduce the biological variability due to differences in flow
      velocity and in light conditions within each sampling section, and consequently
      to take into account only the changes due to water chemistry, nine plates (three
      per sampling section) subjected to similar physical conditions were chosen, and
      the results for these plates were compared with those obtained for all 24 plates.
      As shown by DGGE and by HPLC analyses, using these three substrate plates exposed
      to similar environmental conditions did indeed reduce the within-section
      variability and maximize the between-section variability. This sampling strategy
      also improved the evaluation of the impact of pollutants on the periphytic
      communities, measured using short-term sensitivity testing.

PMID- 19161432
TI  - Graph models of habitat mosaics.
AB  - Graph theory is a body of mathematics dealing with problems of connectivity,
      flow, and routing in networks ranging from social groups to computer networks.
      Recently, network applications have erupted in many fields, and graph models are
      now being applied in landscape ecology and conservation biology, particularly for
      applications couched in metapopulation theory. In these applications, graph nodes
      represent habitat patches or local populations and links indicate functional
      connections among populations (i.e. via dispersal). Graphs are models of more
      complicated real systems, and so it is appropriate to review these applications
      from the perspective of modelling in general. Here we review recent applications
      of network theory to habitat patches in landscape mosaics. We consider (1) the
      conceptual model underlying these applications; (2) formalization and
      implementation of the graph model; (3) model parameterization; (4) model testing,
      insights, and predictions available through graph analyses; and (5) potential
      implications for conservation biology and related applications. In general, and
      for a variety of ecological systems, we find the graph model a remarkably robust
      framework for applications concerned with habitat connectivity. We close with
      suggestions for further work on the parameterization and validation of graph
      models, and point to some promising analytic insights.

PMID- 19161433
TI  - Visualization of Pseudomonas genomic structure by abundant 8-14mer
      oligonucleotides.
AB  - Under- and over-represented mono- to hexanucleotides are signatures of bacterial
      genomes, but the compositional biases of octa- to tetradecanucleotides have not
      yet been explored. Thirteen completely sequenced genomes of the Pseudomonas genus
      were searched for highly overrepresented 8-14mers. Between 59-989 overrepresented
      8-14mers were found to exceed the applied threshold value. All genomic data sets
      of the 13 strains showed a consistent pattern, with individual oligomers
      clustering in either non-coding or coding regions. Non-coding oligonucleotides
      were typically part of longer repeats. Coding oligonucleotides were evenly
      distributed in the core genome, preferred one reading frame and matched with the
      local tetranucleotide usage patterns. Genomic islands were recognized by the
      depletion of overrepresented oligonucleotides. Several mainly coding 8-14mers
      occurred in genomes on average every 10 000 bp or less. Such frequently occurring
      8-14mers could become useful markers for species identification. In the future of
      next-generation ultra-high throughput DNA sequencing, the composition of
      bacterial metagenomes may be quantified by scanning the primary sequence reads
      for these 8-14mer markers.

PMID- 19161434
TI  - Inactivation of mismatch repair increases the diversity of Vibrio
      parahaemolyticus.
AB  - Inactivation of mismatch repair (MMR) has been shown to increase the accumulation
      of spontaneous mutations and frequency of recombination for diverse pathogenic
      bacteria. Currently, little is known regarding the role of mutator phenotypes for
      the diversification of natural populations of opportunistic human pathogens in
      marine environments. In this study, a higher frequency of mutators was detected
      among V. parahaemolyticus strains obtained from environmental sources compared
      with clinical sources. Inactivation of the MMR gene mutS caused increased
      antibiotic resistance and phase variation resulting in translucent colony
      morphologies. Increased nucleotide diversity in mutS and rpoB alleles from
      mutator compared with wild-type strains indicated a significant contribution of
      the mutator phenotype to the evolution of select genes. The results of this study
      indicate that the inactivation of MMR in V. parahaemolyticus leads to increased
      genetic and phenotypic diversity. This study is the first to report a higher
      frequency of natural mutators among Vibrio environmental strains and to provide
      evidence that inactivation of MMR increases the diversity of V. parahaemolyticus.

PMID- 19161435
TI  - Biogeographical distribution of diverse anaerobic ammonium oxidizing (anammox)
      bacteria in Cape Fear River Estuary.
AB  - Anaerobic ammonium oxidation (anammox) specific PCR method was developed to
      examine diversity and distribution of anammox bacteria in sediments collected
      from three different sites at Cape Fear River Estuary, North Carolina, where
      environmental parameters vary greatly over the year. Abundance and activities of
      anammox bacteria in these sediments were measured using the quantitative PCR (Q
      PCR) method and (15)N isotope tracer incubations. Different anammox bacterial
      communities composed with Brocadia, Kuenenia, Jettenia or Scalindua were found
      among sites along the estuarine gradient. Seasonal variations of anammox
      community structures were observed along the estuary based on terminal
      restriction fragment length polymorphism (T-RFLP) analysis of 16S rRNA genes.
      Correlation analysis suggested that salinity variation influenced the diversity
      and distribution of different anammox bacteria in the estuary. Q-PCR assays of
      anammox bacteria showed temporal and spatial variations of their abundances,
      which were highly correlated to salinity variation. (15)N isotope tracer
      incubations measured different anammox rates and its per cent contribution to
      total N(2) production among sites. The highest anammox rate was found at the site
      where Scalindua organisms dominated with the highest anammox bacterial abundance.
      Thus, we demonstrated a biogeographical distribution of diverse anammox bacteria
      influenced by salinity, and provide evidence to link anammox abundance and
      activities in estuarine sediments.

PMID- 19161443
TI  - Saccharomyces boulardii inhibits lipopolysaccharide-induced activation of human
      dendritic cells and T cell proliferation.
AB  - Saccharomyces boulardii (Sb) is a probiotic yeast preparation that has
      demonstrated efficacy in inflammatory and infectious disorders of the
      gastrointestinal tract in controlled clinical trials. Although patients clearly
      benefit from treatment with Sb, little is known on how Sb unfolds its anti
      inflammatory properties in humans. Dendritic cells (DC) balance tolerance and
      immunity and are involved critically in the control of T cell activation. Thus,
      they are believed to have a pivotal role in the initiation and perpetuation of
      chronic inflammatory disorders, not only in the gut. We therefore decided to
      investigate if Sb modulates DC function. Culture of primary (native, non-monocyte
      derived) human myeloid CD1c+CD11c+CD123(-) DC (mDC) in the presence of Sb culture
      supernatant (active component molecular weight < 3 kDa, as evaluated by membrane
      partition chromatography) reduced significantly expression of the co-stimulatory
      molecules CD40 and CD80 (P < 0.01) and the DC mobilization marker CC-chemokine
      receptor CCR7 (CD197) (P < 0.001) induced by the prototypical microbial antigen
      lipopolysaccharide (LPS). Moreover, secretion of key proinflammatory cytokines
      such as tumour necrosis factor-alpha and interleukin (IL)-6 were notably reduced,
      while the secretion of anti-inflammatory IL-10 increased. Finally, Sb supernatant
      inhibited the proliferation of naive T cells in a mixed lymphocyte reaction with
      mDC. In summary, our data suggest that Sb may exhibit part of its anti
      inflammatory potential through modulation of DC phenotype, function and migration
      by inhibition of their immune response to bacterial microbial surrogate antigens
      such as LPS.

PMID- 19161444
TI  - Functional aspects of Toll-like receptor/MyD88 signalling during protozoan
      infection: focus on Toxoplasma gondii.
AB  - Toll-like receptor (TLR)/MyD88 signalling has emerged as a major pathway of
      pathogen recognition in the innate immune system. Here, we review recent data
      that begin to show how this pathway controls the immune response to protozoan
      infection, with particular emphasis on the opportunistic pathogen Toxoplasma
      gondii. The various ways that the parasite activates and suppresses TLR/MyD88
      signalling defines several key principals that illuminate the complexities of the
      host-pathogen interaction. We also speculate how TLR/MyD88 signalling might be
      exploited to provide protection against Toxoplasma, as well as other protozoa and
      infection in general.

PMID- 19161447
TI  - Cross-disciplinary demands of multihost pathogens.
AB  - The dynamics of infectious disease spread depend on host population contact
      structure. Heterogeneities in this contact structure can arise from various forms
      of demographic and spatial phenomena. Craft et al. (this issue) have constructed
      an exploratory simulation model of the spread of canine distemper virus through a
      multispecies carnivore community. Each species in this community is modelled with
      a contact structure reflecting host social organization, ranging behaviour, and
      likely interspecific contact patterns. The results are used to infer the possible
      roles of different species in determining the observed spatio-temporal incidence
      of canine distemper virus in Serengeti lions during an outbreak in 1993-94.

PMID- 19161445
TI  - Relevance of cytotoxic alloreactivity under different immunosuppressive regimens
      in clinical islet cell transplantation.
AB  - Islet or beta cell transplantation provides a promising cure for type 1 diabetes
      patients, but insulin-independency decreases frequently over time.
      Immunosuppressive regimens are implemented attempting to cope with both auto- and
      alloimmunity after transplantation. We analysed the influence of different
      immunotherapies on autoreactive and alloreactive T cell patterns and transplant
      outcome. Patients receiving three different immunosuppressive regimens were
      analysed. All patients received anti-thymocyte globulin induction therapy. Twenty
      one patients received tacrolimus-mycophenolate mofetil maintenance
      immunosuppression, whereas the other patients received tacrolimus-sirolimus (SIR,
      n = 5) or SIR only (n = 5). Cellular autoreactivity and alloreactivity (CTL
      precursor frequency) were measured ex vivo. Clinical outcome in the first 6
      months after transplantation was correlated with immunological parameters. C
      peptide levels were significantly different between the three groups studied (P =
      0.01). We confirm that C-peptide production was correlated negatively with
      pretransplant cellular autoreactivity and low graft size (P = 0.001, P = 0.007
      respectively). Combining all three therapies, cellular autoimmunity after
      transplantation was not associated with delayed insulin-independence or C-peptide
      production. In combined tacrolimus-SIR and SIR-treated patients, CTL
      alloreactivity was associated with less insulin independence and C-peptide
      production (P = 0.03). The percentage of donors to whom high CTLp frequencies
      were measured was lower in insulin-independent recipients (P = 0.03). In this
      cohort of islet cell graft recipients, clinical outcome in the first 6 months
      after transplantation correlates with the applied immunosuppressive regimen. An
      association exists between insulin-independence and lower incidence of CTL
      alloreactivity towards donor human leucocyte antigen. This observational study
      demonstrates the usefulness of monitoring T cell reactivity against islet
      allografts to correlate immune function with graft survival.

PMID- 19161448
TI  - 'A review of extinction in experimental populations' by Blaine Griffen and John
      Drake.

PMID- 19161451
TI  - Preclinical pharmacology of robenacoxib: a novel selective inhibitor of
      cyclooxygenase-2.
AB  - This manuscript reports the results of preclinical studies in the rat with
      robenacoxib, a novel selective cyclooxygenase (COX)-2 inhibitor. Robenacoxib
      selectively inhibited COX-2 in vitro as evidenced from COX-1:COX-2 IC50 ratios of
      27:1 in purified enzyme preparations and >967:1 in isolated cell assays. Binding
      to COX-1 was rapid and readily reversible (dissociation t(1/2) << 1 min), whilst
      COX-2 binding was slowly reversible (t(1/2) = 25 min). In vivo, robenacoxib
      inhibited PGE2 production (an index of COX-2 inhibition) in lipopolysaccharide
      (LPS)-stimulated air pouches (ID50 0.3 mg/kg) and for at least 24 h in zymosan
      induced inflammatory exudate (at 2 mg/kg). Robenacoxib was COX-1 sparing, as it
      inhibited serum TxB2 synthesis ex vivo (an index of COX-1 inhibition) only at
      very high doses (100 mg/kg but not at 2-30 mg/kg). Robenacoxib inhibited
      carrageenan-induced paw oedema (ID50 0.40-0.48 mg/kg), LPS-induced fever (ID50
      1.1 mg/kg) and Randall-Selitto pain (10 mg/kg). Robenacoxib was highly bound to
      plasma protein (99.9% at 50 ng/mL in vitro). After intravenous dosing, clearance
      was 2.4 mL/min/kg and volume of distribution at steady-state was 306 mL/kg.
      Robenacoxib was preferentially distributed into inflammatory exudate; the AUC for
      exudate was 2.9 times higher than for blood and the MRT in exudate (15.9 h) was
      three times longer than in blood (5.3 h). Robenacoxib produced significantly less
      gastric ulceration and intestinal permeability as compared with the reference
      nonsteroidal anti-inflammatory drug (NSAID), diclofenac, and did not inhibit PGE2
      or 6-keto PGF(1alpha) concentrations in the stomach and ileum at 30 mg/kg.
      Robenacoxib also had no relevant effects on kidney function at 30 mg/kg. In
      summary, results of preclinical studies in rats studies suggest that robenacoxib
      has an attractive pharmacological profile for potential use in the intended
      target species, cats and dogs.

PMID- 19161452
TI  - Use of a pharmacokinetic/pharmacodynamic approach in the cat to determine a
      dosage regimen for the COX-2 selective drug robenacoxib.
AB  - This study investigated the analgesic, anti-inflammatory and antipyretic efficacy
      of the new COX-2 selective inhibitor robenacoxib in the cat and established
      pharmacodynamic (PD) parameters for these effects. Robenacoxib, at a dosage of 2
      mg/kg administered subcutaneously, was evaluated in a kaolin-induced paw
      inflammation model in 10 cats, using both clinically relevant endpoints (lameness
      scoring, locomotion tests) and other indicators of inflammation (body and skin
      temperature, thermal pain threshold) to establish its pharmacological profile. A
      pharmacokinetic/pharmacodynamic (PK/PD) modelling approach, based on indirect
      response models, was used to describe the time course and magnitude of the
      responses to robenacoxib. All endpoints demonstrated good responsiveness to
      robenacoxib administration and both the magnitude and time courses of responses
      were well described by the indirect pharmacodynamic response models.
      Pharmacokinetic and clinically relevant pharmacodynamic parameters were used to
      simulate dosage regimens that will assist the planning of clinical trials and the
      selection of an optimal dosage regimen for robenacoxib in the cat.

PMID- 19161453
TI  - Differential inhibition of cyclooxygenase isoenzymes in the cat by the NSAID
      robenacoxib.
AB  - Robenacoxib is a new nonsteroidal anti-inflammatory drug (NSAID) developed for
      use in companion animal medicine. The objectives of this study were: to quantify
      the inhibitory actions of robenacoxib on cyclooxygenase (COX) isoenzymes in
      feline whole blood assays; to establish blood concentration-time profiles of
      robenacoxib after intravenous and subcutaneous dosing in the cat and; to predict
      the time courses of inhibition of COX isoforms by robenacoxib. COX-1 and COX-2
      activities in heparinized feline whole blood samples were induced with calcium
      ionophore and lipopolysaccharide, respectively. Inhibition of thromboxane B2
      provided a marker of both COX-1 and COX-2 activities and a nonlinear parametric
      mixed effects modelling approach was used to establish the pharmacodynamic
      parameters describing this inhibition. Mean values (and prediction intervals) of
      IC50 were 28.9 (16.4-51.1) microM (COX-1) and 0.058 (0.010-0.340) microM (COX-2).
      These parameters were used to compute several selectivity indices. Selectivity IC
      ratios (COX-1:COX-2) were 502.3 (IC50/IC50), 451.6 (IC95/IC95) and 17.05
      (IC20/IC80). Based on a clinically recommended dosage regimen of 2 mg/kg, it was
      predicted that the corresponding mean robenacoxib blood concentration over the
      first 12 h after drug administration corresponded to 5% inhibition of COX-1 and
      90% inhibition of COX-2.

PMID- 19161454
TI  - Analytical determination and pharmacokinetics of robenacoxib in the dog.
AB  - An analytical method was developed and validated for the measurement of the novel
      analgesic and anti-inflammatory drug robenacoxib in blood and plasma of dogs and
      cats. To prevent nonreproducible carry-over effects, an initial solid phase
      extraction procedure was followed by high pressure liquid chromatography analysis
      for samples with concentrations in the range 500 to 20,000 ng/mL. To improve
      accuracy, samples of concentration 3 to 100 ng/mL were analyzed by liquid
      chromatography-mass spectrometry. Applying these methods, blood concentration
      time profiles and pharmacokinetic variables of robenacoxib in dogs were
      determined in a four-phase cross-over study, which compared different routes of
      administration of the drug, including intravenous (i.v.) injection, oral
      application with and without feed, and subcutaneous (s.c.) application. After
      i.v. administration the mean clearance from blood was 0.81 L/kg/h, the volume of
      distribution was 0.77 L/kg for the elimination phase and 0.24 L/kg for steady
      state, and the terminal half-life in blood was 0.63 h. Maximum blood
      concentrations were obtained in less than 1 h following oral or s.c. application.
      Absolute bioavailability was 88% after s.c. injection, 84% after oral
      administration to fasted dogs, but was reduced to 62% when applied orally to fed
      dogs. In canine and feline plasma the degree of binding of robenacoxib to plasma
      protein in vitro was greater than 98%. The blood:plasma concentration ratio was
      0.44:1 in the dog and 0.65:1 in the cat. In conclusion analytical methods for the
      quantification of robenacoxib in blood and plasma in the dog and cat were
      developed and validated. In dogs, robenacoxib has good bioavailability after oral
      (84%) and subcutaneous (88%) administration.

PMID- 19161455
TI  - Enantiomeric disposition of ketorolac in goats following administration of a
      single intravenous and oral dose.
AB  - The purpose of this study was to investigate the stereospecific pharmacokinetics
      of ketorolac (KT) in goats following a single 2 mg/kg intravenous (i.v.) dose and
      a single 6 mg/kg oral dose. A stereoselective high pressure liquid chromatography
      assay was used to quantify ketorolac plasma concentrations. Pharmacokinetic
      parameters for both stereoisomers were estimated by model independent methods.
      Following an i.v. dose, the plasma concentration profiles for the stereoisomers
      were similar with half-lives of 1.05 +/- 0.62 h for R-KT and 1.05 +/- 0.61 h for
      S-KT. Clearance values for R- and S-KT after an i.v. dose were 0.53 +/- 0.23 and
      0.54 +/- 0.23 L.h/kg, respectively. Following an oral dose, the terminal half
      lives were longer with values of 34.08 +/- 11.81 and 33.97 +/- 12.19 h for R-KT
      and S-KT, respectively. The average bioavailability was 133 +/- 23% for R-KT and
      S-KT, respectively. The longer half-lives and high apparent bioavailability after
      oral dosing are suggestive of a slow absorption process in the gastrointestinal
      tract and recycling. The results indicate that interconversion of the
      stereoisomers of ketorolac is absent in goats. However, studies with individual
      isomers are needed before any conclusion can be drawn about the lack of
      bioinversion.

PMID- 19161456
TI  - Tissue residue depletion of oxytetracycline after repeated intramuscular
      administration of Oxysentin 100 in sheep.
AB  - The depletion profile of oxytetracycline was studied in healthy sheep after
      intramuscular administration of Oxysentin 100, given at a dose of 10 mg
      oxytetracycline per kg body weight once daily for 5 consecutive days. Five
      medicated sheep were slaughtered at 0, 2, 4, 6, 9 and 12 days postmedication, and
      injection site, muscle, fat, liver and kidney tissues were sampled and analysed
      using a liquid chromatographic method, which was fully validated for
      oxytetracycline and 4-epi-oxytetracycline. At day 0 postmedication, the
      concentrations of oxytetracycline marker residue (sum of oxytetracycline and 4
      epi-oxytetracycline) in all tissues examined were at the mg/kg level. At day 2
      postmedication, the concentrations of oxytetracycline marker residue in all
      injection site and kidney samples examined were higher than the corresponding
      maximum residue limits (MRLs) established by the European Union, while the
      concentrations in muscle and liver tissues of two and three out of five animals
      examined, respectively, were below the corresponding MRLs. At days 4 and 6
      postmedication, concentrations of oxytetracycline marker residue above the MRLs
      were found only in the injection site, whereas at day 9 postmedication, all
      observations were below the corresponding MRLs.

PMID- 19161457
TI  - Pharmacokinetics of butorphanol in horses after intramuscular injection.
AB  - A two-way cross-over study of the pharmacokinetics of butorphanol after
      intravenous and intramuscular administration at 0.08 mg/kg in six adult horses
      was performed. Heparinized venous blood samples were obtained prior to drug
      administration and at 10, 20, 30, 45, 60, 120, 180, 240, and 360 min after IV
      injection. Samples were obtained at the same time points and at 6 h and 12 h
      after IM injection. Physical examination parameters were recorded at each time
      point. Plasma butorphanol concentrations were determined by high performance
      liquid chromatography. No significant differences in any physical parameters were
      observed after butorphanol administration except for an increase in respiratory
      rate at 60 and 180 min after IV administration. Absorption of butorphanol after
      IM administration was very rapid (half life of absorption of 6 min) but systemic
      availability after IM injection was low (37%). Terminal half-life after IV
      administration was much longer than half-life after IM administration (0.57 h and
      7.7 h, respectively). This difference was attributed to detection of a deep
      compartment after IV administration that was not detectable after IM
      administration. To maintain targeted plasma butorphanol concentrations above 10
      ng/mL, administration of 0.08 mg/kg IM every 3 h may be necessary.

PMID- 19161458
TI  - Pyrilamine in the horse: detection and pharmacokinetics of pyrilamine and its
      major urinary metabolite O-desmethylpyrilamine.
AB  - Pyrilamine is an antihistamine used in human and veterinary medicine. As
      antihistamines produce central nervous system effects in horses, pyrilamine has
      the potential to affect the performance of racehorses. In the present study, O
      desmethylpyrilamine (O-DMP) was observed to be the predominant equine urinary
      metabolite of pyrilamine. After intravenous (i.v.) administration of pyrilamine
      (300 mg/horse), serum pyrilamine concentrations declined from about 280 ng/mL at
      5 min postdose to about 2.5 ng/mL at 8 h postdose. After oral administration of
      pyrilamine (300 mg/horse), serum concentrations peaked at about 33 ng/mL at 30
      min, falling to <2 ng/mL at 8 h postdose. Pyrilamine was not detected in serum
      samples at 24 h postdosing by either route. After i.v. injection of pyrilamine
      (300 mg/horse) O-DMP was recovered at a level of about 20 microg/mL at 2 h
      postdose thereafter declining to about 2 ng/mL at 168 h postdose. After oral
      administration, the O-DMP recovery peaked at about 12 microg/mL at 8 h postdose
      and declined to <2 ng/mL at 168 h postdose. These results show that pyrilamine is
      poorly bioavailable orally (18%), and can be detected by sensitive enzyme-linked
      immunosorbent assay tests in urine for up to 1 week after a single
      administration. Care should be taken as the data suggest that the withdrawal time
      for pyrilamine after repeated oral administrations is likely to be at least 1
      week or longer.

PMID- 19161459
TI  - Inhibition of cytochrome P450 activity enhances the systemic availability of
      triclabendazole metabolites in sheep.
AB  - Understanding the disposition kinetics and the pattern of metabolism is critical
      to optimise the flukicidal activity of triclabendazole (TCBZ) in ruminants. TCBZ
      is metabolised by both flavin-monooxygenase (FMO) and cytochrome P450 (P450) in
      the liver. Interference with these metabolic pathways may be useful to increase
      the systemic availabilities of TCBZ metabolites, which may improve the efficacy
      against Fasciola hepatica. The plasma disposition of TCBZ metabolites was
      evaluated following TCBZ co-administration with FMO [methimazole (MTZ)] and P450
      [piperonyl butoxyde (PB) and ketoconazole (KTZ)] inhibitors in sheep. Twenty (20)
      healthy Corriedale x Merino weaned female lambs were randomly allocated into four
      experimental groups. Animals of each group were treated as follow: Group A, TCBZ
      alone (5 mg/kg, IV route); Group B, TCBZ (5 mg/kg, IV) + MTZ (3 mg/kg, IV); Group
      C, TCBZ (5 mg/kg, IV) + PB (30 mg/kg, IV) and Group D, TCBZ (5 mg/kg, IV) + KTZ
      (10 mg/kg, orally). Blood samples were taken over 240 h post-treatment and
      analysed by HPLC. TCBZ sulphoxide and sulphone were the main metabolites
      recovered in plasma. MTZ did not affect TCBZ disposition kinetics. TCBZ
      sulphoxide Cmax values were significantly increased (P < 0.05) after the TCBZ +
      PB (62%) and TCBZ + KTZ (37%) treatments compared to those measured in the TCBZ
      alone treatment. TCBZ sulphoxide plasma AUCs were higher (P < 0.05) in the
      presence of both PB (99%) and KTZ (41%). Inhibition of TCBZ P450-mediated
      oxidation in the liver accounted for the increased systemic availability of its
      active metabolite TCBZ sulphoxide. This work contributes to the search of
      different strategies to improve the use of this flukicidal drug in ruminants.

PMID- 19161460
TI  - Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and
      bcrp- deficient knockout mice.
AB  - P-glycoprotein, which is encoded by the multi-drug resistance gene (MDR1), highly
      restricts the entry of ivermectin into the brain by an ATP-driven efflux
      mechanism at the blood-brain barrier. In dogs with a homozygous MDR1 mutation
      though, ivermectin accumulates in the brain and provokes severe signs of
      neurotoxicosis and even death. In contrast to ivermectin, selamectin is safer in
      the treatment of MDR1 mutant dogs, suggesting that selamectin is transported
      differently by P-glycoprotein across the blood-brain barrier. To test this, we
      applied selamectin to mdr1-deficient mdr1a,b(-/-) knockout mice and wild-type
      mice. Brain penetration, organ distribution, and plasma kinetics were analyzed
      after intravenous, oral, and dermal spot-on application in comparison with
      ivermectin. We found that in vivo both macrocyclic lactone compounds are
      substrates of P-glycoprotein and that these strongly accumulate in the brain of
      mdr1a,b(-/-) knockout mice compared with wild-type mice at therapeutic doses of
      12 mg/kg selamectin and 0.2 mg/kg ivermectin. However, selamectin accumulates to
      a much lesser degree (5-10 times) than ivermectin (36-60 times) in the absence of
      P-glycoprotein. This could explain the broader margin of safety of selamectin in
      MDR1 mutant dogs. In liver, kidney, and testes, ivermectin and selamectin
      accumulated less than four times as much in mdr1a,b mutant mice as in wild-type
      mice. Breast cancer resistance protein (Bcrp)-deficient bcrp(-/-) knockout mice
      were also included in the application studies, but showed no differences in brain
      concentrations or organ distribution of either ivermectin or selamectin compared
      with wild-type mice. This indicates that Bcrp is not a relevant efflux carrier
      for these macrocyclic lactone compounds in vivo at the blood-brain barrier.

PMID- 19161461
TI  - Pharmacokinetics of tepoxalin and its active metabolite in broiler chickens.

PMID- 19161462
TI  - Pharmacokinetics, urinary excretion and milk penetration of levofloxacin in
      lactating goats.

PMID- 19161463
TI  - Pharmacokinetics of danofloxacin following intravenous and intramuscular
      administration in donkeys.

PMID- 19161464
TI  - On the validity of habitat as a predictor of genetic structure in aquatic
      systems: a comparative study using California water beetles.
AB  - Among freshwater organisms, water flow is frequently considered to be one of the
      most important environmental variables affecting life-history traits such as
      dispersal abilities and therefore genetic structure. Recent studies have
      suggested that habitat type alone as defined by water flow is predictive of
      genetic population differentiation, while others have advocated against broad
      generalizations in favour of more conservative, species-specific conclusions. If
      aquatic habitat type is predictive of population differentiation, then one would
      expect sympatric taxa that occupy the same aquatic habitat to converge on a
      similar genetic structure. We tested this prediction by examining the haplotype
      diversity, phylogeographical concordance, population connectivity and population
      isolation of three lotic water beetle species in southern California: Anacaena
      signaticollis, Eubrianax edwardsii and Stictotarsus striatellus. In addition to
      coarse habitat and geography, we also controlled for the potentially confounding
      factors of range size, method of dispersal and clade independence. Together, the
      species spanned extremes of genetic and phylogeographical structure in all
      measures examined, suggesting that a coarse dichotomy of aquatic habitat type is
      not predictive of genetic structure. While there is little question that water
      flow plays a major role in shaping the life-history traits of freshwater
      organisms, it is perilous to confer predictive properties to an artificially
      simplistic dichotomy or use it as a surrogate for other unmeasured variables.

PMID- 19161465
TI  - Proteomic and phenotypic profiling of the amphibian pathogen Batrachochytrium
      dendrobatidis shows that genotype is linked to virulence.
AB  - Population genetics of the amphibian pathogen Batrachochytrium dendrobatidis (Bd)
      show that isolates are highly related and globally homogenous, data that are
      consistent with the recent epidemic spread of a previously endemic organism.
      Highly related isolates are predicted to be functionally similar due to low
      levels of heritable genetic diversity. To test this hypothesis, we took a global
      panel of Bd isolates and measured (i) the genetic relatedness among isolates,
      (ii) proteomic profiles of isolates, (iii) the susceptibility of isolates to the
      antifungal drug caspofungin, (iv) the variation among isolates in growth and
      phenotypic characteristics, and (v) the virulence of isolates against the
      European common toad Bufo bufo. Our results show (i) genotypic differentiation
      among isolates, (ii) proteomic differentiation among isolates, (iii) no
      significant differences in susceptibility to caspofungin, (iv) differentiation in
      growth and phenotypic/morphological characters, and (v) differential virulence in
      B. bufo. Specifically, our data show that Bd isolates can be profiled by their
      genotypic and proteomic characteristics, as well as by the size of their
      sporangia. Bd genotypic and phenotypic distance matrices are significantly
      correlated, showing that less-related isolates are more biologically unique. Mass
      spectrometry has identified a set of candidate genes associated with inter
      isolate variation. Our data show that, despite its rapid global emergence, Bd
      isolates are not identical and differ in several important characters that are
      linked to virulence. We argue that future studies need to clarify the
      mechanism(s) and rate at which Bd is evolving, and the impact that such variation
      has on the host-pathogen dynamic.

PMID- 19161466
TI  - Effects of dynamic landscape elements on fish dispersal: the example of creek
      chub (Semotilus atromaculatus).
AB  - Barriers along a watercourse and interconnections between drainage systems are
      dynamic landscape elements that are expected to play major roles in the dispersal
      and genetic structure of fish species. The objective of this study was to assess
      the role of these elements using creek chub (Semotilus atromaculatus) in the
      Mastigouche Wildlife Reserve (Quebec, Canada) as model. Numerous impassable
      waterfalls and interconnections among drainage systems were inferred with
      geographic information systems and confirmed de visu. The analysis of 32
      populations using seven nuclear microsatellites revealed the presence of three
      genetically distinct groups. Some groups were found upstream of impassable
      barriers and in adjacent portions of distinct drainage systems. Admixture among
      groups was also detected in some populations. Constraining phylogenetic
      procedures as well as Mantel correlation tests confirmed that the genetic
      structure is more likely to result from interconnections between the drainage
      systems than from the permanent network. This study indicates that landscape
      elements such as interconnections are of major importance for circumventing
      impassable barriers and colonizing lakes that are otherwise inaccessible. Such an
      approach could be relevant for determining the origins of fish species (i.e.
      native vs. introduced) in the context of conservation.

PMID- 19161467
TI  - Fine- and regional-scale genetic structure of the exotic ascidian Styela clava
      (Tunicata) in southwest England, 50 years after its introduction.
AB  - Styela clava, an ascidian native to the northwest Pacific, was first recorded in
      the Atlantic at Plymouth, southwest England, in 1953. It now ranges in the
      northeast Atlantic from Portugal to northern Denmark, and has colonized the east
      coast of North America. Within the region of first introduction, we aimed to
      characterize current genetic diversity in the species, elucidate the respective
      roles of human-aided vs. natural dispersal, and assess the extent of larval
      dispersal by looking for genetic differentiation at very small scales. Eight
      sites, mostly marinas, were studied along c. 200 km of coast in southwest England
      encompassing Plymouth. Five microsatellite loci were genotyped in 303 individuals
      to analyse gene flow at regional (among sites) and fine (within sites) scales. F
      statistics and assignment tests were used to investigate regional genetic
      structure. At the fine scale, deviation from mutation-drift equilibrium was
      tested, and isolation by distance and genetic clustering analyses were
      undertaken. Significant genetic differentiation existed between sites, unrelated
      to geographical separation; migration between geographically distant marinas was
      inferred, highlighting the likely importance of human-mediated dispersal in range
      expansion and occupancy by S. clava. Fine-scale population structure was present
      within at least four sites, which may be explained by the limited dispersal
      ability of this ascidian and recruitment from differentiated pools of larvae.
      Populations in enclosed marinas had higher self-recruitment rates than those in
      open sites. Some marinas might therefore function as reservoirs of propagules for
      subsequent spread, whereas others might be sinks for migrants.

PMID- 19161468
TI  - Discordance between phylogenetics and coalescent-based divergence modelling:
      exploring phylogeographic patterns of speciation in the Carex macrocephala
      species complex.
AB  - We fit a molecular data set, consisting of the rpL16 cpDNA marker and eight
      microsatellite loci, to the isolation-with-migration model as implemented in IMa
      to test a well-supported phylogenetic hypothesis of relationships within the
      Carex macrocephala species complex (Cyperaceae). The phylogenetic hypothesis
      suggests C. macrocephala from North America is reciprocally monophyletic and is
      sister to a reciprocally monophyletic clade of C. kobomugi. The North American C.
      macrocephala and C. kobomugi clade form a sister clade with a lineage of Asian C.
      macrocephala, thereby forming a paraphyletic C. macrocephala species. Not only
      does the phylogenetic hypothesis suggest C. macrocephala is paraphyletic, but it
      also suggests that the two lineages which share a partially overlapping
      distribution, Asian C. macrocephala and C. kobomugi, are not the most closely
      related. To test these relationships, we used coalescent-based population genetic
      models to infer divergence time for each lineage pair within the species complex.
      The coalescent-based models account for the stochastic forces which drive
      population divergence, and can account for the lineage sorting that occurs prior
      to lineage divergence. A drawback to phylogenetic-based phylogeographical
      analyses is that they do not account for stochastic lineage sorting that occurs
      between gene divergence and lineage divergence. By comparing the relative
      divergence time of the three main lineages within this group, Asian C.
      macrocephala, North American C. macrocephala, and C. kobomugi, we concluded that
      the phylogenetic hypothesis is incorrect, and the divergence between these
      lineages occurred during the Late Pleistocene epoch.

PMID- 19161469
TI  - Variable responses of skinks to a common history of rainforest fluctuation:
      concordance between phylogeography and palaeo-distribution models.
AB  - There is a growing appreciation of impacts of late-Quaternary climate
      fluctuations on spatial patterns of species and genetic diversity. A major
      challenge is to understand how and why species respond individualistically to a
      common history of climate-induced habitat fluctuation. Here, we combine modelling
      of palaeo-distributions and mitochondrial-DNA phylogeographies to compare spatial
      patterns of population persistence and isolation across three species of
      rainforest skinks (Saproscincus spp.) with varying climatic preferences. Using
      Akaike Information Criterion model-averaged projections, all three species are
      predicted to have maintained one or more small populations in the northern Wet
      Tropics, multiple or larger populations in the central region, and few if any in
      the south. For the high-elevation species, Saproscincus czechurai, the warm-wet
      climate of the mid Holocene was most restrictive, whereas for the generalist S.
      basiliscus and lower-elevation S. tetradactyla, the cool-dry last glacial maximum
      was most restrictive. As expected, S. czechurai was the most genetically
      structured species, although relative to modelled distributions, S. basiliscus
      had surprisingly deep phylogeographical structure among southern rainforest
      isolates, implying long-term isolation and persistence. For both S. basiliscus
      and S. tetradactyla, there was high genetic diversity and complex
      phylogeographical patterns in the central Wet Tropics, reflecting persistence of
      large, structured populations. A previously identified vicariant barrier
      separating northern and central regions is supported, and results from these
      species also emphasize a historical persistence of populations south of another
      biogeographical break, the Tully Gorge. Overall, the results support the
      contention that in a topographically heterogeneous landscape, species with
      broader climatic niches may maintain higher and more structured genetic diversity
      due to persistence through varying climates.

PMID- 19161470
TI  - Cohesive molecular genetic data delineate species diversity in the dinoflagellate
      genus Symbiodinium.
AB  - The diversity of symbiotic dinoflagellates (Symbiodinium) in pocilloporid corals
      originating from various reef habitats surrounding Heron Island, southern Great
      Barrier Reef, was examined by targeting ribosomal, mitochondrial, and chloroplast
      genes using six methods that analyse for sequence differences. The ability of
      each of 13 genetic analyses to characterize eight ecologically distinct
      Symbiodinium spp. was dependent on the level of conservation of the gene region
      targeted and the technique used. Other than differences in resolution,
      phylogenetic reconstructions using nuclear and organelle gene sequences were
      complementary and when combined produced a well-resolved phylogeny. Analysis of
      the ribosomal internal transcribed spacers using denaturing gradient gel
      electrophoresis fingerprinting in combination with sequencing of dominant bands
      provided a precise method for rapidly resolving and characterizing symbionts into
      ecologically and evolutionarily distinct units of diversity. Single-stranded
      conformation polymorphisms of the nuclear ribosomal large subunit (D1/D2 domain)
      identified the same number of ecologically distinct Symbiodinium spp., but
      profiles were less distinctive. The repetitive sequencing of bacterially cloned
      ITS2 polymerase chain reaction amplifications generated numerous sequence
      variants that clustered together according to the symbiont under analysis. The
      phylogenetic relationships between these clusters show how intragenomic variation
      in the ribosomal array diverges among closely related eukaryotic genomes. The
      strong correlation between phylogenetically independent lineages with different
      ecological and physiological attributes establishes a clear basis for assigning
      species designations to members of the genus Symbiodinium.

PMID- 19161471
TI  - Hybridization between mouse lemurs in an ecological transition zone in southern
      Madagascar.
AB  - Hybrid zones in ecotones can be useful model systems for the study of
      evolutionary processes that shape the distribution and discreteness of species.
      Such studies could be important for an improved understanding of the complex
      biogeography of Madagascar, which is renowned for its outstanding degree of small
      scale endemism. Certain forest remnants in central Madagascar indicate that
      transitional corridors across the island could have connected microendemics in
      different forest types in the past. Evolutionary processes in such corridors are
      difficult to study because most of these corridors have disappeared due to
      deforestation in central Madagascar. We studied a hybrid zone in one of the few
      remaining ecotonal corridors between dry and humid forests in Madagascar, which
      connects two species of mouse lemurs, Microcebus griseorufus in dry spiny forest
      and Microcebus murinus in humid littoral forest. We sampled 162 mouse lemurs at
      nine sites across this boundary. Morphometric analyses revealed intermediate
      morphotypes of many individuals in transitional habitat. Bayesian clustering of
      microsatellite genotypes and assignment tests yielded evidence for a mixed
      ancestry of mouse lemurs in the ecotone, where we also observed significant
      linkage disequilibria and heterozygote deficiency. In contrast to these
      observations, mitochondrial haplotypes displayed a sharply delimited boundary at
      the eastern edge of spiny forest, which was noncoincident with the signals from
      microsatellite data. Among several alternative scenarios, we propose asymmetric
      nuclear introgression due to male-biased dispersal, divergent environmental
      selection, and an expansion of dry spiny forest in the course of aridification as
      a probable explanation of our observations.

PMID- 19161472
TI  - Inferring the past to predict the future: climate modelling predictions and
      phylogeography for the freshwater gastropod Radix balthica (Pulmonata,
      Basommatophora).
AB  - Understanding the impact of past climatic events on species may facilitate
      predictions of how species will respond to future climate change. To this end, we
      sampled populations of the common pond snail Radix balthica over the entire
      species range (northwestern Europe). Using a recently developed analytical
      framework that employs ecological niche modelling to obtain hypotheses that are
      subsequently tested with statistical phylogeography, we inferred the range
      dynamics of R. balthica over time. A Maxent modelling for present-day conditions
      was performed to infer the climate envelope for the species, and the modelled
      niche was used to hindcast climatically suitable range at the last glacial
      maximum (LGM) c. 21,000 years ago. Ecological niche modelling predicted two
      suitable areas at the LGM within the present species range. Phylogeographic model
      selection on a COI mitochondrial DNA data set confirmed that R. balthica most
      likely spread from these two disjunct refuges after the LGM. The match observed
      between the potential range of the species at the LGM given its present climatic
      requirements and the phylogeographically inferred refugial areas was a clear
      argument in favour of niche conservatism in R. balthica, thus allowing to predict
      the future range. The subsequent projection of the potential range under a global
      change scenario predicts a moderate pole-ward shift of the northern range limits,
      but a dramatic loss of areas currently occupied in France, western Great Britain
      and southern Germany.

PMID- 19161473
TI  - Global population structure of the tope (Galeorhinus galeus) inferred by
      mitochondrial control region sequence data.
AB  - In order to properly manage and conserve exploited shark species, detailed
      analyses of their population structure is needed. Global populations of
      Galeorhinus galeus are in decline due to the exploitation of the fishery over the
      past 80 years. Currently, the genetic structure of eastern Pacific populations of
      G. galeus is not known and recent observations in the northeastern Pacific
      suggest an increase in numbers. To evaluate gene flow among populations of G.
      galeus, 116 samples were collected and analysed from six geographically dispersed
      locations: Australia, North America, South Africa, South America (Argentina and
      Peru), and the UK. Analysis of 968 to 1006 bp of the 1068-bp mitochondrial
      control region revealed 38 unique haplotypes that were largely restricted to
      their collecting locality. Significant genetic structure was detected among
      populations (Phi(ST) = 0.84; P < 0.000001) and migration estimates were low (Nm =
      0.05-0.97). Due to an apparent lack of migration, populations of G. galeus appear
      to be isolated from each other with little to no gene flow occurring among them.
      As a consequence of this isolation, increasing numbers of G. galeus in the
      northeastern Pacific can be best explained by local recruitment and not by input
      from geographically distant populations.

PMID- 19161474
TI  - Levels of specificity of Xylaria species associated with fungus-growing termites:
      a phylogenetic approach.
AB  - Fungus-growing termites live in obligate mutualistic symbiosis with species of
      the basidiomycete genus Termitomyces, which are cultivated on a substrate of dead
      plant material. When the termite colony dies, or when nest material is incubated
      without termites in the laboratory, fruiting bodies of the ascomycete genus
      Xylaria appear and rapidly cover the fungus garden. This raises the question
      whether certain Xylaria species are specialised in occupying termite nests or
      whether they are just occasional visitors. We tested Xylaria specificity at four
      levels: (1) fungus-growing termites, (2) termite genera, (3) termite species, and
      (4) colonies. In South Africa, 108 colonies of eight termite species from three
      termite genera were sampled for Xylaria. Xylaria was isolated from 69% of the
      sampled nests and from 57% of the incubated fungus comb samples, confirming high
      prevalence. Phylogenetic analysis of the ITS region revealed 16 operational
      taxonomic units of Xylaria, indicating high levels of Xylaria species richness.
      Not much of this variation was explained by termite genus, species, or colony;
      thus, at level 2-4 the specificity is low. Analysis of the large subunit rDNA
      region, showed that all termite-associated Xylaria belong to a single clade,
      together with only three of the 26 non-termite-associated strains. Termite
      associated Xylaria thus show specificity for fungus-growing termites (level 1).
      We did not find evidence for geographic or temporal structuring in these Xylaria
      phylogenies. Based on our results, we conclude that termite-associated Xylaria
      are specific for fungus-growing termites, without having specificity for lower
      taxonomic levels.

PMID- 19161476
TI  - Avoiding confounded comparisons in education research.

PMID- 19161477
TI  - A missed opportunity.

PMID- 19161478
TI  - Medical expertise: begin with the end in mind.

PMID- 19161479
TI  - Optimal sequencing of bedside teaching and computer-based learning: a randomised
      trial.
AB  - OBJECTIVES: We aimed to establish the most effective order in which to deliver
      teaching to medical students when using both bedside teaching (BT) and computer
      based learning (CBL) and to ascertain the students' preferred method and order of
      delivery. METHODS: A sample of 28 medical students were randomly divided into two
      equal groups during their orthopaedic knee examination teaching session. Group 1
      received standard BT and group 2 undertook a CBL package. Each group then
      undertook an objective structured clinical examination (OSCE). The groups then
      received the other method of teaching followed by another OSCE. A questionnaire
      was administered to all students to assess their views on, and preferences for,
      the various teaching methods. RESULTS: Mean scores on the first OSCE were 12.19
      for group 1 (BT then CBL) and 11.96 for group 2 (CBL then BT) (P = 0.692). Mean
      scores on the second OSCE were 11.81 for group 1 compared with 12.79 for group 2
      (P = 0.038). Statistical analysis showed a significantly better score improvement
      for group 2 (CBL then BT) over group 1 (BT then CBL). Of the 26 students who
      returned questionnaires, 24 (92%) expressed their preference for traditional BT
      over CBL only, and 23 (88%) were in favour of undertaking CBL prior to
      traditional BT. CONCLUSIONS: The CBL package is a useful tool and is most
      effective if used before BT. Students prefer BT alone over CBL alone, but, if
      offered both, prefer to undertake CBL first.

PMID- 19161480
TI  - Peer-assisted versus faculty staff-led skills laboratory training: a randomised
      controlled trial.
AB  - OBJECTIVES: Although peer-assisted learning (PAL) is widely employed throughout
      medical education, its effectiveness for training in technical procedures in
      skills laboratories has been subject to little systematic investigation. We
      conducted a prospective, randomised trial to evaluate the hypotheses that PAL is
      effective in technical skills training in a skills laboratory setting, and PAL is
      as effective as faculty staff-led training. METHODS: Volunteer Year 3 medical
      students were randomly assigned to one of three groups. Two of these received
      regular skills training from either cross-year peer tutors or experienced faculty
      staff. Following training, both groups were assessed using an objective
      structured clinical examination (OSCE) (three stations assessing various
      injection techniques) which was video-recorded. Two independent video assessors
      scored the OSCEs using binary checklists and global ranking forms. A third
      student group was assessed prior to training and served as a control group.
      RESULTS: A total of 89 students (mean age 23.0 +/- 0.2 years; 41 male, 48 female)
      agreed to participate in the trial. Confounding variables including prior
      training as a paramedic or previous experience in performing the technical
      procedures did not significantly differ between the three study groups. In the
      OSCE, PAL (58.1 +/- 1 binary points, 4.9 +/- 0.1 global ranking points) and
      faculty-led groups (58.3 +/- 1 binary points, 4.7 +/- 0.1 global ranking points)
      scored significantly higher than the control group (33.3 +/- 1 binary points, 2.7
      +/- 0.1 global ranking points; all P < 0.0001). There was no significant
      difference between the PAL and faculty-led groups (P = 0.92 for binary
      checklists, P = 0.11 for global rankings). CONCLUSIONS: Peer-assisted learning is
      a successful method for learning technical procedures in a skills laboratory
      setting and can be just as effective as the training provided by experienced
      faculty staff.

PMID- 19161481
TI  - Electives: isn't it time for a change?
AB  - OBJECTIVES: Medical student electives are memorable learning experiences, of
      which approximately 40% are spent in developing countries. Students often have
      laudable motivation but are rarely helped to learn most effectively or contribute
      meaningfully whilst away. Each year an estimated 350 years of elective time is
      spent in developing countries (by students from the UK alone), which represents
      substantial opportunity. METHODS: We conducted a literature search prior to
      developing an alternative approach towards electives based upon educational and
      ethical principles. RESULTS: Despite their anecdotal value there has been little
      empirical research conducted into electives. From our review we identified four
      key learning domains (Clinical Knowledge and Skills, Attitudes, Global
      Perspectives, Personal and Professional Development) and two broader issues
      (Institutional Benefits and Moral/Ethical Considerations). Potentially beneficial
      and more structured alternatives are emerging and improvements appear possible
      through institutional collaborations and greater planning in order to maximise
      the educational experience, opportunities to contribute and minimise the risks
      involved in electives. CONCLUSIONS: Electives are a highlight of clinical
      training but probably often represent missed opportunities. There are both
      educational and moral reasons for seeking more considered approaches to reduce
      the 'medical tourism' that can result from the current largely ad hoc
      arrangements.

PMID- 19161482
TI  - How student models of expertise and innovation impact the development of adaptive
      expertise in medicine.
AB  - OBJECTIVES: The ability to innovate new solutions in response to daily workplace
      challenges is an important component of adaptive expertise. Exploring how to
      optimally develop this skill is therefore of paramount importance to education
      researchers. This is certainly no less true in health care, where optimal patient
      care is contingent on the continuous efforts of doctors and other health care
      workers to provide the best care to their patients through the development and
      incorporation of new knowledge. Medical education programmes must therefore
      foster the skills and attitudes necessary to engage future doctors in the
      systematic development of innovative problem solving. The aim of this paper is to
      describe the perceptions and experiences of medical students in their third and
      fourth years of training, and to explore their understanding of their development
      as adaptive experts. METHODS: A sample of 25 medical students participated in
      individual 45-60-minute semi-structured interviews. Interviews were audiotaped,
      transcribed and entered into NVivo qualitative data analysis software to
      facilitate a thematic analysis. The analysis was both inductive, in that themes
      were generated from the data, and deductive, in that our data were meaningful
      when interpreted in the context of theories of adaptive expertise. RESULTS:
      Participants expressed a general belief that, as learners in the health care
      system, exerting any effort to be innovative was beyond the scope of their
      responsibilities. Generally, students suggested that innovative practice was the
      prerogative of experts and an outcome of expert development centred on the
      acquisition of knowledge and experience. CONCLUSIONS: Students' perceptions of
      themselves as having no responsibility to be innovative in their learning process
      have implications for their learning trajectories as adaptive experts.

PMID- 19161483
TI  - Factors influencing treatment for depression among medical students: a nationwide
      sample in South Korea.
AB  - OBJECTIVES: Depression is more frequently experienced and induces more severe
      consequences in medical students than in the general population. However,
      treatment rates for depression in medical students are still low. In this study,
      the authors investigated factors that affect treatment for depression and
      dispositions towards treating depression among South Korean medical students.
      METHODS: A nationwide, cross-sectional survey was administered to medical
      students attending all 41 medical schools in South Korea (14,095 students). The
      questionnaire included the Beck Depression Inventory (BDI) and asked for data on
      socio-demographic variables, history of diagnosis or treatment for depression,
      knowledge of mental health problems and disposition to use mental health care.
      RESULTS: A total of 7357 students (52.2%) from 36 schools responded to the
      survey. Of these, 689 (9.4%) were identified as being depressed via a BDI score
      higher than 16. Of the depressed respondents, only 61 (8.9%) had been diagnosed
      with depression and 67 (9.7%) had been treated for depression. Age was
      significantly associated with treatment behaviour for depression. Correct
      knowledge about the aetiology of depression and psychiatric medicine was
      significantly related to students' disposition to use psychiatric services and to
      receive psychopharmacotherapy as an option to resolve depression. CONCLUSIONS:
      Accurate knowledge of depression and appropriate medication seems to be relevant
      to students seeking appropriate treatment for depression. The development of
      education programmes designed to improve medical students' knowledge of mental
      health problems and treatments would facilitate treatment seeking in medical
      students.

PMID- 19161484
TI  - Testing an empirically derived mental health training model featuring small
      groups, distributed practice and patient discussion.
AB  - OBJECTIVES: Internationally, family doctors seeking to enhance their skills in
      evidence-based mental health treatment are attending brief training workshops,
      despite clear evidence in the literature that short-term, massed formats are not
      likely to improve skills in this complex area. Reviews of the educational
      literature suggest that an optimal model of training would incorporate
      distributed practice techniques; repeated practice over a lengthy time period,
      small-group interactive learning, mentoring relationships, skills-based training
      and an ongoing discussion of actual patients. This study investigates the
      potential role of group-based training incorporating multiple aspects of good
      pedagogy for training doctors in basic competencies in brief cognitive behaviour
      therapy (BCBT). METHODS: Six groups of family doctors (n = 32) completed eight 2
      hour sessions of BCBT group training over a 6-month period. A baseline control
      design was utilised with pre- and post-training measures of doctors' BCBT skills,
      knowledge and engagement in BCBT treatment. RESULTS: Family doctors' knowledge,
      skills in and actual use of BCBT with patients improved significantly over the
      course of training compared with the control period. CONCLUSIONS: This research
      demonstrates preliminary support for the efficacy of an empirically derived group
      training model for family doctors. Brief CBT group-based training could prove to
      be an effective and viable model for future doctor training.

PMID- 19161485
TI  - Mentioning race at the beginning of clinical case presentations: a survey of US
      medical schools.
AB  - OBJECTIVES: Medical students and doctors in the USA frequently mention the
      patient's race at the beginning of oral or written clinical case presentations.
      However, this practice is controversial. We aimed to determine whether US medical
      schools explicitly teach students to mention race at the beginning of case
      presentations, and to collect additional information on the schools' perspectives
      on this practice. METHODS: An Internet-based questionnaire was submitted to
      directors of courses on history taking and physical examination at all US medical
      schools. RESULTS: The response rate was 85%. Students are taught to mention race
      routinely at 11% of schools and selectively at 63% of schools; this practice is
      discouraged at 9% of schools and not addressed at 18% of schools. Most
      respondents noted that resident doctors at their institutions routinely mention
      race at the beginning of case presentations. Even at schools in which mentioning
      race is discouraged or not addressed, students tend to include race during their
      clinical rotations. Respondents were divided on whether a standardised approach
      to inclusion of race should exist at US schools. CONCLUSIONS: Teaching about
      inclusion or exclusion of race in the opening statement of clinical case
      presentations varies across US medical schools. This variation presents an
      opportunity for medical educators to discuss tensions between stereotyping and
      cultural competence in medical education.

PMID- 19161486
TI  - Mentorship in postgraduate training programmes: views of Canadian programme
      directors.
AB  - OBJECTIVES: Many academic training programmes have developed mentorship
      programmes for postgraduate doctors in training, but little is known about the
      factors that influence their establishment. METHODS: Canadian postgraduate
      training directors were surveyed to determine views on mentorship and factors
      associated with the establishment of these programmes. RESULTS: A total of 199 of
      344 (58%) programme directors completed an online survey. Overall, 65% of
      respondents reported that their training programmes had a mentorship programme
      and 40% felt there was a need for more structured mentorship in training
      programmes. Univariate analysis showed that mentorship programmes were present
      significantly more often in larger programmes, internal medicine-based training
      programmes, and in programmes where the acting programme director had either been
      part of a mentorship programme during his or her own training or felt that
      mentorship had played an important role in his or her professional development.
      In adjusting for covariates using a logistic regression analysis, only those
      factors directly attributable to a programme director's personal mentoring
      experiences remained significantly associated with having a mentorship programme.
      Those who felt that mentorship had played a role in their own careers (P = 0.008,
      odds ratio [OR] = 3.3, 95% confidence interval [CI] 1.7-6.6) or who had been part
      of a mentorship programme during their own training (P = 0.01, OR = 6.6, 95% CI
      1.4-30.1) were more likely to have an active mentorship programme at their
      institution. CONCLUSIONS: A need for more structured mentorship was identified
      for many training programmes. Overall, programme directors' previous mentoring
      experiences were independently associated with having a mentorship programme.

PMID- 19161487
TI  - Effects of multi-source feedback on developmental plans for leaders of
      postgraduate medical education.
AB  - OBJECTIVES: Multi-source feedback (MSF) is a widely used developmental tool for
      leaders in organisations including those dealing with health care. This study was
      performed to examine the effects of an MSF process on developmental plans made by
      leaders of postgraduate medical education (PGME) in clinical departments.
      METHODS: An MSF instrument was developed based on literature on the subject and
      previous investigations. The instrument was used by consultants responsible for
      PGME in clinical departments (CREs). Apart from CREs' self-ratings, MSF responses
      were collected from heads of departments, consultants and young doctors-in
      training. The MSF process included individual feedback as well as guidance on
      drafting developmental plans for both the department and the CREs. Themes
      emerging in the developmental plans were analysed and compared with the areas in
      need of improvement identified by the MSF process. RESULTS: The MSF instrument
      was found to be feasible, valid and reliable (Cronbach's alpha = 0.98). The study
      included 52 CREs from various specialties and 498 MSF respondents. The response
      rate was 84%. Low ratings and negative gaps between others' ratings and self
      ratings were identified for both management and leadership performance areas. The
      developmental plans mainly focused on management initiatives, whereas plans for
      the development of leadership performance were few. Areas rated low by all
      respondents were scarcely represented in CREs' developmental plans. CONCLUSIONS:
      An MSF process might in itself lead to development in administrative areas.
      However, MSF carried through as a single stand-alone procedure was not sufficient
      to foster plans for the development of leadership performance.

PMID- 19161488
TI  - The multiple mini-interview: how long is long enough?
AB  - OBJECTIVES: The multiple mini-interview (MMI) overcomes the limitations of the
      traditional panel interview by multiple sampling to provide improved objectivity
      and reliability. Reliability of the MMI is affected by number of stations;
      however, there are few data reporting the influence of interview duration on MMI
      outcome and reliability. We aimed to determine whether MMI stations can be
      shortened without affecting applicant rankings or compromising test reliability.
      METHODS: A total of 175 applicants were interviewed and assessed at 10 8-minute
      stations. Applicants were scored once after 8 minutes at five control stations
      and twice after 5 minutes and 8 minutes at five experimental stations. Scores at
      5 and 8 minutes were compared using t-tests and correlation coefficients.
      Rankings of applicants based on 5- and 8-minute scores were compared using
      Spearman's rank order coefficient. The reliability of the MMI was examined for 5-
      and 8-minute scores using generalisability theory. RESULTS: Mean scores at 5
      minutes were lower than mean scores at 8 minutes. Cumulative scores at 5 minutes
      were also lower. There were highly significant correlations between 5- and 8
      minute scores at all experimental stations (0.82-0.91; P < 0.01) and between the
      cumulative scores at 5 and 8 minutes (0.92; P < 0.01). There was a strong
      correlation between applicant rankings based on cumulative 5- and 8-minute scores
      (Spearman's rank order coefficient 0.92). Reliability was not affected.
      CONCLUSIONS: Reducing the duration of MMI stations from 8 to 5 minutes conserves
      resources with minimal effect on applicant ranking and test reliability.

PMID- 19161489
TI  - Selection of medical students: a controlled experiment.
AB  - OBJECTIVES: We aimed to discover, through a controlled experiment, whether
      cognitive and non-cognitive assessment would select higher-achieving applicants
      to medical school than selection by lottery. METHODS: We carried out a
      prospective cohort study to compare 389 medical students who had been admitted by
      selection and 938 students who had been admitted by weighted lottery, between
      2001 and 2004. Main outcome measures were dropout rates, study rate (credits per
      year) and mean grade per first examination attempt per year. Study rates in the 4
      pre-clinical years of medical school were used to categorise students'
      performance as average or optimal. RESULTS: Pre-admission variables did not
      differ between the two groups. The main outcome of the selection experiment was
      that relative risk for dropping out of medical school was 2.6 times lower for
      selected students than for lottery-admitted controls (95% confidence interval
      1.59-4.17). Significant differences between the groups in the percentage of
      optimally performing students and grade point average for first examination
      attempts were found only in the 2001 cohort, when results favoured the selected
      group. The results of the selection process took into account both the assessment
      procedure involved and the number of students who withdrew voluntarily.
      CONCLUSIONS: This is the first controlled study to show that assessing
      applicants' non-cognitive and cognitive abilities makes it possible to select
      students whose dropout rate will be lower than that of students admitted by
      lottery. The dropout rate in our overall cohort was 2.6 times lower in the
      selected group.

PMID- 19161490
TI  - Student views on the effective teaching of physical examination skills: a
      qualitative study.
AB  - OBJECTIVES: The lack of published studies into effective skills teaching in
      clinical skills centres inspired this study of student views of the teaching
      behaviours of skills teachers. METHODS: We organised focus group discussions with
      students from Years 1-3 of a 6-year undergraduate medical curriculum. A total of
      30 randomly selected students, divided into three groups, took part in two
      sessions. They discussed what teaching skills helped them to acquire physical
      examination skills. RESULTS: Students' opinions related to didactic skills,
      interpersonal and communication skills and preconditions. Students appreciated
      didactic skills that stimulate deep and active learning. Another significant set
      of findings referred to teachers' attitudes towards students. Students wanted
      teachers to be considerate and to take them seriously. This was reflected in
      student descriptions of positive behaviours, such as: 'responding to students'
      questions'; 'not exposing students' weaknesses in front of the group', and '[not]
      putting students in an embarrassing position in skill demonstrations'. They also
      appreciated enthusiasm in teachers. Important preconditions included: the
      integration of skills training with basic science teaching; linking of skills
      training to clinical practice; the presence of clear goals and well-structured
      sessions; good time management; consistency of teaching, and the appropriate
      personal appearance of teachers and students. CONCLUSIONS: The teaching skills
      and behaviours that most facilitate student acquisition of physical examination
      skills are interpersonal and communication skills, followed by a number of
      didactic interventions, embedded in several preconditions. Findings related to
      interpersonal and communication skills are comparable with findings pertaining to
      the teaching roles of tutors and clinical teachers; however, the didactic skills
      merit separate attention as teaching skills for use in skills laboratories. The
      results of this study should be complemented by a study performed in a larger
      population and a study exploring teachers' views.

PMID- 19161492
TI  - Rural health research.

PMID- 19161491
TI  - The sodium-dependent D-glucose transport protein of Helicobacter pylori.
AB  - Helicobacter pylori is a gram-negative pathogenic microaerophile with a
      particular tropism for the mucosal surface of the gastric epithelium. Despite its
      obligatory microaerophilic character, it can metabolize D-glucose and/or D
      galactose in both oxidative and fermentative pathways via a Na(+)-dependent
      secondary active transport, a glucokinase and enzymes of the pentose phosphate
      pathway. We have assigned the Na(+)-dependent transport of glucose to the protein
      product of the H. pylori 1174 gene. The gene was heterologously expressed in a
      glucose transport-deficient Escherichia coli strain, where transport activities
      of radiolabelled D-glucose, D-galactose and 2-deoxy-D-glucose were restored,
      consistent with the expected specificity of the hexose uptake system in H.
      pylori. D-mannose was also identified as a substrate. The HP1174 transport
      protein was purified and reconstituted into proteoliposomes, where sodium
      dependence of sugar transport activity was demonstrated. Additionally the
      tryptophan/tyrosine fluorescence of the purified protein showed quenching by 2
      deoxy-D-glucose, D-mannose, D-glucose or D-galactose in the presence of sodium
      ions. This is the first reported purification and characterization of an active
      glucose transport protein member of the TC 2.1.7 subgroup of the Major
      Facilitator Superfamily, constituting the route for entry of sugar nutrients into
      H. pylori. A model is derived of its three-dimensional structure as a paradigm of
      the family.

PMID- 19161493
TI  - Health status differentials across rural and remote Australia.
AB  - This paper describes mortality and disease patterns across five broad remoteness
      categories of Australia, with reference to the context in which those outcomes
      develop and are treated. Health and its outcomes become worse as remoteness
      increases. Some of this phenomenon reflects proportionally greater numbers of
      Aboriginal and Torres Strait Islander people in remote areas coupled with their
      poorer overall health outcomes; however, mortality for non-indigenous people is
      clearly higher outside compared with inside major cities. Migration of people
      seeking services likely reduces the size of interregional health disparity.
      Poorer health outcomes stem from worse risk factor profiles and average lower
      levels of income and of education, poorer physical and financial access to
      services, higher occupational and environmental risk, as well as factors unique
      to Aboriginal and Torres Strait Islander health. Little is known about the health
      benefits of living outside major cities. Diseases of the circulatory system and
      injuries account, respectively, for 40% and 18% of the excess mortality outside
      major cities. Death rates are declining over time in all (particularly remote)
      areas, but rates of death due to certain lung diseases in rural women are not,
      and rates of suicide have increased in remote areas. Ostensibly, prevalence of
      mental ill-health appears roughly similar in all remoteness areas. Dental health
      is poorer and disability is more prevalent outside major cities, as are a range
      of infectious diseases. Although pertinent, the effects on rural health of
      climate change and resource degradation generally have not been addressed in this
      paper.

PMID- 19161494
TI  - Influence of socioeconomic and cultural factors on rural health.
AB  - OBJECTIVE: To provide a framework for investigating the influence of
      socioeconomic and cultural factors on rural health. DESIGN: Discussion paper.
      RESULTS: Socioeconomic and cultural factors have long been thought to influence
      an individual's health. We suggest a framework for characterising these factors
      that comprises individual-level (e.g. individual socioeconomic status, sex, race)
      and neighbourhood-level dimensions (population composition, social environment,
      physical environment) operating both independently and through interaction.
      Recent spatial research suggests that in rural communities, socioeconomic
      disadvantage and indigenous status are two of the greatest underlying influences
      on health status. However, rural communities also face additional challenges
      associated with access to, and utilisation of, health care. The example is given
      of procedural angiography for individuals with an acute coronary event.
      CONCLUSIONS: Socioeconomic and cultural factors specific to rural Australia are
      key influences on the health of residents. These range from individual-level
      factors, such as rural stoicism, poverty and substance use norms, to
      neighbourhood-level social characteristics, such as lack of services, migration
      out of rural areas of younger community members weakening traditionally high
      levels of social cohesion, and to environmental factors, such as climate change
      and access to services.

PMID- 19161495
TI  - Impact of rurality on environmental determinants and hazards.
AB  - The original of this paper was prepared as invited pre-reading for the Inaugural
      Rural Health Symposium held in Brisbane in July 2008 under the theme "The impact
      of 'rurality'", sub-theme (a) Environmental determinants. The natural environment
      shapes human activity, both economically and socially. It also directly and
      indirectly influences health and well-being. People in rural and remote areas are
      more directly exposed to the natural environment than their urban counterparts.
      The built environment is largely a product of economic activity; thus, the built
      environment in rural areas tends to reflect the predominant primary industry/ies.
      The rural built environment presents many potential hazards and risks to health
      and well-being, particularly for those involved in the primary industries, which
      are either not present in urban areas, or are present on smaller or more
      contained scales. The natural and built environments also influence individuals'
      attitudes and behaviours, both positively and negatively. The environmental
      determinants of rural health, therefore, can be considered in terms of the
      natural environment, the built environment and individuals' responses to
      environmental influences. This paper raises some of the common environmental
      determinants of rural health and well-being and briefly touches on what these
      mean for rural health service delivery.

PMID- 19161496
TI  - Innovative rural and remote primary health care models: what do we know and what
      are the research priorities?
AB  - This paper examines the literature pertaining to 'innovative' primary health care
      models in rural and remote areas in order to identify areas where knowledge is
      lacking and describes future research priorities. Although a number of reviews
      have identified successful primary health care models and synthesised principles
      that help to understand why they are successful, there is generally a dearth of
      rigorously collected information regarding rural and remote health service
      delivery. The evidence base that supports the superiority of any one model or
      models in a given context is thin because of the lack of systematic, policy
      informing evaluation of primary care innovations. The paper identifies the need
      for more rigorous health services evaluation information, including examination
      of optimal financing systems, the optimal range and mix of providers, and
      supports for team practice, appropriate community participation mechanisms,
      improved health information systems and relevant performance indicators.

PMID- 19161497
TI  - Integration and coordination of care.
AB  - The health care systems in Australia are under pressure from workforce shortages,
      increasing costs and an ageing population with a high prevalence of chronic
      disease. There is a well-established description of inequity in health outcomes
      among rural and remote populations. Most of the inequity appears to be due to
      poorer access to services than higher levels of health risk factors, such as
      cholesterol, blood pressure or obesity. Over the last 15 years, the science of
      improvement has led to quality improvement techniques, such as collaboratives,
      managed clinical networks and collaborative care, all of which have been tried
      successfully in Australia. Each of these offers ways to reduce the inequity in
      health outcomes attributed to rurality or remoteness.

PMID- 19161498
TI  - Key considerations in delivering appropriate and accessible health care for rural
      and remote populations: discussant overview.
AB  - OBJECTIVE: To provide an overview of papers discussing optimal service delivery
      models for rural and remote Australia. DESIGN: A synthesis of overarching
      considerations guiding rural and remote health service policies. SETTING: Small
      rural and remote communities in Australia. PARTICIPANTS: Invited delegates
      attending the Inaugural Rural and Remote Health Scientific Symposium in Brisbane
      2008. MAIN OUTCOME MEASURES: Key issues underpinning health service provision for
      small rural and remote communities. RESULTS: The formulation and implementation
      of effective health service provision policies must be underpinned by overarching
      health goals, agreed health service requirements, recognition of how rural and
      remote health contexts impact upon health service provision and the constraints
      limiting health service responses. CONCLUSION: Systemic change is required in
      order to ensure equitable access to health care services in small rural and
      remote communities.

PMID- 19161499
TI  - Multi-level rural community engagement in health.
AB  - Community participation in health is consistent with notions of democracy. A
      systems perspective of engagement can see consumers engaged to legitimise
      government agendas. Often community participation is via consultation instead of
      partnership or delegation. A community development approach to engagement can
      empower communities to take responsibility for their own health care.
      Understanding rural place facilitates alignment between health programs and
      community, assists in incorporating community resources into health care and
      provides information about health needs. Rural communities, health services and
      other community organisations need skills in working together to develop
      effective partnerships that transfer some power from health systems. Rural
      engagement with national/state agendas is a challenge. Community engagement takes
      time and resources, but can be expected to lead to better health outcomes for
      rural residents.

PMID- 19161500
TI  - Multidisciplinary management of complex care.
AB  - Rural and remote areas of Australia are facing serious health workforce
      shortages. Multidisciplinary teams are one way of making the most of the rural
      workforce. In this paper, the advantages of multidisciplinary care in terms of
      patient outcomes, clinician satisfaction and system efficiency are considered
      with reference to an innovative rural multidisciplinary model that highlights how
      these positive outcomes can be achieved. Ways of developing the capacity of the
      future workforce for work in multidisciplinary teams are discussed.

PMID- 19161501
TI  - Impact of rurality on health practices and services: summary paper to the
      inaugural rural and remote health scientific symposium.
AB  - This summary paper for the symposium provides a brief overview of the papers by
      Craig Veitch, John Beard and Max Kamien that deal with the environmental,
      socioeconomic and political descriptors of 'rurality'. Those three papers deal
      with a number of fundamental truths about rural and remote health, including the
      fact that internal migration is an important and poorly understood factor in
      determining community and health outcomes. A brief treatment of the issue
      suggests that selective internal migration is likely to mean that the burden of
      illness in rural and remote areas is even higher than that suggested by the
      published figures. The paper then asserts that thinking in the rural and remote
      health sector in Australia focuses largely on the negative aspects of the current
      characteristics of rural areas. A self-evident definition of 'rurality' is
      offered that has it defined by the set of factors that currently characterise
      places, communities and individuals outside the major cities. The paper suggests
      that each of these characteristics has an upside or benefit, as well as a
      downside or risk, and that giving greater attention to the former will provide a
      better basis for informing rural health policy and practice than the deficit view
      alone.

PMID- 19161502
TI  - Evaluating the outcomes of rural health policy.
AB  - With the development of policies specifically relating to rural health and health
      care provision, it seems apposite to consider evaluating their outcomes. Although
      little has apparently been done that specifically studies policy or processes,
      much of rural health research implicitly 'measures' policy effects; for example,
      study of the effects of rural medical education. Given what is known about the
      policy-making process, rural health researchers should beware of thinking that
      policy outcome evaluation might be straightforward or that evidence produced from
      evaluation will seamlessly influence future or evolving policy. Nonetheless, as
      rural health research and policy mature, it is worth adopting some of the complex
      approaches to health policy outcome measurement and applying them to understand
      our field--to find out the extent that policy, and indeed our role and research,
      have effects on rural health and care provision. In this paper, we identify some
      of the quirks of policy and policy evaluation and provide examples.

PMID- 19161503
TI  - Rural-urban disparities in health: how does Canada fare and how does Canada
      compare with Australia?
AB  - OBJECTIVE: To analyse rural-urban and intra-rural disparities in health status in
      Canada and to compare Canada with Australia with respect to such disparities.
      DESIGN: Four indicators were used to show rural-urban and intra-rural differences
      in health status: (i) mortality due to circulatory diseases, (ii) mortality due
      to cancer, (iii) injury-related mortality; and (iv) all-cause mortality. Rural
      was disaggregated into finer categories based on degree of remoteness, using the
      Metropolitan Influence Zone classification in Canada and the
      Accessibility/Remoteness Index of Australia. Comparisons were made using age
      standardised mortality rates and standardised mortality ratios. PARTICIPANTS:
      Rural and urban populations of Canada and Australia. RESULTS: The study confirmed
      previous findings that rural Canadians tended to have poorer health status than
      their urban counterparts. However, when rural was disaggregated into finer
      categories, different health status patterns emerged. Although the most rural
      areas tended to have the worst health status, the least rural areas generally
      enjoyed good health. The Canada-Australia comparisons revealed convergence and
      divergence. CONCLUSIONS: The similarities between Canada and Australia show that
      rural-urban disparities in health status are not limited to a particular country.
      For several causes of death, whereas the mortality risks in Rural 1 areas in
      Canada are significantly lower than in urban areas, the opposite is true in
      Australia, suggesting that although there are some common patterns across the two
      countries in relation to rural-urban health status disparities, nation-specific
      uniqueness is to be expected.

PMID- 19161504
TI  - Evidence-based policy versus evidence-based rural health care reality checks.

PMID- 19161507
TI  - Selective publication and its impact on clinical knowledge.

PMID- 19161508
TI  - Cerebral extension of steroid-responsive meningitis arteritis in a boxer.
AB  - A comatose 30-month-old, entire male boxer was presented because of an acute
      history of a cluster of three to four seizures. Neurological examination
      suggested a diffuse to multifocal intracranial lesion. Magnetic resonance
      tomography revealed symmetrical multifocal to diffuse changes of the cerebral
      grey matter and ependymal lining with sediment in the lateral ventricles.
      Haematological examination revealed leucocytosis with neutrophilia. Cerebrospinal
      fluid examination revealed high protein concentration and polymorphonuclear
      pleocytosis. Despite antiepileptic treatment, therapy against increased
      intracranial pressure and antibiosis, the dog's condition continued to
      deteriorate and he was euthanased. Pathological examination revealed
      fibrinosuppurative meningo-ependymitis and necrotising arteritis throughout the
      brain. In addition, chronic inflammation and arterial stenosis was found in the
      spinal meninges. No infectious agent was found. A diagnosis of steroid-responsive
      meningitis arteritis was made. The massive extension into the meninges and
      ventricular system of the forebrain has not been described previously in dogs
      with steroid-responsive meningitis arteritis and should be considered in the
      differential diagnosis when an intracranial suppurative infection is suspected.

PMID- 19161510
TI  - Examining the heritability of anal sac gland carcinoma in cocker spaniels.

PMID- 19161511
TI  - VIIIth International Conference of the Journal of Analytical Psychology.
      'Tradition and Creativity: Reframing Analysis in a Changing World'.

PMID- 19161512
TI  - Man in the age of technology.
AB  - This paper argues that technology is no longer merely a tool for man's use but
      has become the environment in which man undergoes modifications. The author
      traces the role of technology from the Greeks to the present day. For the Greeks,
      Nature was governed by necessity and therefore unchangeable whereas in the Judeo
      Christian tradition, nature was entrusted to man for him to dominate. Modern
      science studies the world in order to manipulate and dominate nature through the
      use of technology which has now become an end in itself, governing the solution
      of political problems and confronting us with problems beyond our competence to
      resolve. The ethical impact of technology has been to create a change from
      'acting' which assumes responsibility for one's actions to 'doing' which is
      concerned only with the effective execution of a 'job' without concern for the
      wider consequences. It can no longer be argued that technology is good or bad
      according to the use we make of it since technology now makes use of us and thus
      transforms our ethics, social relationships and psychological being.

PMID- 19161513
TI  - Response to Umberto Galimberti.

PMID- 19161514
TI  - When words do not mean what they say. Self-agency and the coercive use of
      language.
AB  - This paper explores the relationship between language and the development of self
      agency. I suggest that a child discovers that he or she actually exists as a
      person with a mind and desires through the mirroring response he or she creates
      in the parent. This developmental stage of 'teleological' level of self-agency is
      related to Terrence Deacon's concept of indexical communication. The coercive
      effect this has on others is explored and the way language may become subverted
      from its symbolic function and used in the service of indexical communication is
      discussed, illustrated by examples from the plays of Harold Pinter.

PMID- 19161515
TI  - Turning on and tuning out: new technology, image, analysis.
AB  - There was a time when the answer-phone was thought too alienating for patients;
      now there is the question of whether therapists feel OK being paid by electronic
      bank transfer. Since the start of modern psychotherapy, new communications
      technology-the telephone, radio, TV, and now electronic messaging-have become
      universally accessible. The question arises: do email, texts and the mobile (cell
      phone) enhance and enable communication or do they merely offer the fantasy of
      doing so? Equally, can computer simulations and software diagnostic and treatment
      programmes offer anything to mental health practice? Furthermore, since the mid
      nineteenth century, the technology of visual communication, in particular,
      paralleled the development of psychodynamic theory and practice. Nowadays,
      photographic images have become so prevalent and available that clients can bring
      pictures in many forms. They also bring movies, movie-scenes and characters,
      either in description or to show, and these may constitute the images and
      material of analysis in some cases just as dreams always have done. How are we to
      respond to these unconventional communications of our clients' emotional lives?
      Are they legitimate expressions of their inner worlds? This paper discusses the
      influence of the new technologies of communication with a special focus on the
      place of film themes and images in psychotherapy and analytic sessions.

PMID- 19161516
TI  - A perspective on the patterns of loss, lack, disappointment and shame encountered
      in the treatment of six women with severe and chronic anorexia nervosa.
AB  - This paper explores how the aggressive fantasies and energies expressed in
      anorexic self-hatred can be recycled to become the basis of psychological growth
      and recovery. This shift is made possible by focusing on the telos of the
      analysand's psychological system as it expresses itself through her illness, and
      using Clark's idea that sanity is a form of recycled madness. It also draws on
      Jung's view of the unconscious as an active and purposive agent, and libido as a
      neutral psychic energy which can serve different purposes. I discuss a number of
      clinical vignettes, focusing on the hard, ruthless, defiant and hateful aspects
      of (what might appear to be) 'monstrous' anorexic behaviour, and the kinds of
      countertransference reactions these behaviours can provoke. I also explore what
      these kinds of behaviours might represent in terms of multi-generational family
      dynamics, as well as mother-daughter dynamics. At the core of the paper is the
      idea that the capacity to use aggression in clear ways, but within the limits of
      conscience, is essential for the protection of one's physical and psychological
      boundaries. Without the capacity to defend oneself, and the ability to decide
      quickly and clearly when it is right to risk hurting the other in order to do so,
      one cannot take any level of risk in life, or draw close to the other. I suggest
      that for recovery from anorexia to occur, the aggressive, self-hateful,
      destructive energies which are so central to the illness need to be recycled into
      these kinds of awarenesses and life-skills.

PMID- 19161517
TI  - 'Tradition and the analytical setting: is there any space for originality in our
      clinical practice?' Introduction to the Panel.

PMID- 19161518
TI  - Music in dreams and the emergence of the self.
AB  - This paper deals with the presence and possible 'meaning' of music in dreams. The
      author explores a possible meaning of music as the most fundamental human
      symbolic experience, which directly points to the emergence of the Self from the
      primal union mystique with the Great Mother. The relationships between acoustic
      and visual experiences are taken into account as two basic human forms of coming
      into existence, although wholly different from each other. The role of music in
      dreams seems to be that of the most direct representation of the emerging Self in
      its pure, pre-representational form. Therefore, when music appears in dreams,
      providing there is the activation of an emotional tone, all other elements-
      visual and verbal--should be considered as the expression of the sense to which
      the music is pointing. A clinical example is described in order to better express
      the author's opinions.

PMID- 19161519
TI  - The session of the two dreams.
AB  - Through the discussion of the clinical material the author tries to show how
      numerous aspects of traditional Jungian analysis are close to several theoretical
      and clinical developments of Relational Psychoanalysis. A short introduction
      about relational psychoanalysis is given. The relational aspects of Jungian
      theory and praxis are underlined. If we refer to these theoretical constructs, it
      becomes possible to work in an original way and think of the clinical setting as
      different from the classical Freudian one, without abandoning Jungian tradition.

PMID- 19161520
TI  - Endnotes: from Orta onward.

PMID- 19161521
TI  - Jung, vitalism and 'the psychoid': an historical reconstruction.
AB  - This paper traces the history of Jung's ideas concerning the psychoid
      unconscious, from their origins in the work of the vitalist, Hans Driesch, and
      his concept of Das Psychoid, through the subsequent work of Eugen Bleuler,
      Director of the Burgholzli Asylum, and his concept of Die Psychoide, to the
      publication of Jung's paper On the Nature of the Psyche in 1947. This involves a
      review of Jung's early work and of his meeting with Freud, when apparently the
      two men discussed calling the unconscious 'psychoid', as well as a review of
      Jung's more mature ideas concerning a psychoid unconscious. I propose to argue
      that even at the time of their meeting, Jung had already formulated an
      epistemological approach that was significantly different from that of Freud and
      that clearly foreshadowed his later ideas as set out in On the Nature of the
      Psyche.

PMID- 19161531
TI  - LDL and UV-oxidized LDL induce upregulation of iNOS and NO in unstimulated J774
      macrophages and HUVEC.
AB  - Oxidized low-density lipoprotein (LDL) diminishes NO production from activated
      macrophages. The interaction between LDL and inactivated macrophages is neglected
      and controversial. This study examines the effect of LDL, 7-oxysterols and iron
      compounds on NO production in unstimulated J774 macrophages. J774 cells and human
      umbilical vein endothelial cells (HUVEC) were either incubated for 24 h with
      native LDL (LDL) or ultraviolet (UV)-oxidized LDL (UVoxLDL), in the absence or
      presence of an inducible nitric oxide synthase (iNOS)- or an endothelial
      constitutive nitric oxide synthase (eNOS)-inhibitor. J774 cells were also
      incubated with lipopolysaccharide (LPS), in the absence or presence of an iNOS-
      or an eNOS-inhibitor. Nitrite was analysed as a marker of NO production. The mRNA
      levels of iNOS were evaluated by reverse transcriptase polymerase chain reaction.
      LDL and UVoxLDL significantly increased NO production from unstimulated J774
      macrophages. This increase in NO was accompanied by enhanced expression of iNOS
      mRNA, and was inhibited by the iNOS inhibitor. Furthermore, NO production was
      elevated and angiotensin-converting enzyme (ACE) activity was reduced in HUVEC
      following the exposure to LDL and UVoxLDL. In conclusion, LDL may serve as an
      important inflammatory activator of macrophages and HUVEC, inducing inducible
      nitric oxide production but diminishing ACE. After its oxidation, this function
      of LDL may be further enhanced and may contribute to the regulation and
      progression of atheroma formation.

PMID- 19161532
TI  - Pathogenesis of equine herpesvirus-1 infection in the mouse model.
AB  - Equine herpesvirus-1 (EHV-1) is a major equine pathogen causing respiratory
      diseases, abortions and severe neurological disorders. The basis of neurological
      disturbances is, as in other organs, infection of endothelial cells, followed by
      vasculitis, thrombosis and ischaemic damage of the parenchyma. Here, a murine
      model was used to explore the mechanism of entry to, and spread within the brain,
      the cell affinity of the agent and the modulating role of the immune defence,
      which are all factors governing the pathogenesis of the neurological disease.
      Because controversial views exist about these mechanisms, we undertook a
      neuropathological study with intranasally infected adult mice. EHV-1 entered the
      brain through the olfactory neuroepithelium and along the olfactory nerves, and
      spread transsynaptically in rostro-caudal direction, using olfactory and limbic
      neuronal networks. Exclusively neurons were infected. The cellular immune
      reaction exerted a restraining effect on virus dissemination. Following nasal
      infection, the olfactory route was the major pathway for virus entry and
      dissemination, involvement of the trigeminal nerve in virus spread seems much
      less probable. In the adult mouse brain EHV-1 behaves as a typical neurotropic
      agent, using, similarly to other herpesviruses, the neuronal networks for
      dissemination. Vasculitis, the predominant type of lesion in natural infection,
      and endothelial cell positivity for EHV-1 were detectable only in the lung. Thus,
      this agent exhibits in the mouse a dual affinity: it is neurotropic in the brain,
      and endotheliotropic in visceral organs. Consideration of pathogenetic aspects of
      equine and experimental murine EHV-1 infections also helps a better understanding
      of human herpetic brain disease.

PMID- 19161533
TI  - A type-specific study of human papillomavirus prevalence in cervicovaginal
      samples in three different Spanish regions.
AB  - Human papillomavirus (HPV) is the most frequent sexually transmitted viral
      infection. It is necessary to know HPV genotype distribution to identify how many
      women will be protected by HPV vaccines. During a period of 18 months, we have
      analyzed 2362 HPV positive reporting data from a secondary demand screening
      program in three regions in Spain (Cantabria, Leon and Burgos). The study has
      been conducted using polymerase chain reaction and tube array hybridization
      covering the 35 HPV genotypes described as affecting anogenital mucosa. There
      were no significant differences between the three regions according to genotype
      distribution. The most frequent were HPV16 (19.18%), HPV53 (11.26%) and HPV58
      (7.66%). HPV18 was the source of 4.02% of infections. High-risk HPVs were found
      in 1863/2362 cases. HPV16 was present in 24.3% of high-risk infections and HPV18
      was found in 5.1%. Uncommon genotypes (<5% of the total prevalence each) were
      found in 17,9% of the total high-risk infections (334/1863). Multiple infections
      were diagnosed in 22% of the cases. The HPV genotype distribution is different
      from previously published data when multiple types are included in the screening.
      Both HPV16/18 account for 30% of high-risk infections in a clinical setting in
      Spain. The presence of multiple genotypes is very common among the population.

PMID- 19161534
TI  - Immunohistochemical analysis of Fas and FLIP in prostate cancers.
AB  - Fas-mediated apoptosis is considered a principal pathway for apoptosis induction
      in normal and cancer cells. Expression of Fas has been reported in prostate
      tissues several times, but the data were not consistent. Expression of FLICE-like
      inhibitory protein (FLIP), an inhibitor of Fas-mediated apoptosis, has not been
      studied by immunohistochemistry in prostate tissues. The aim of this study is to
      explore whether alterations of Fas and FLIP expression occur in prostate cancer
      tissues. We analyzed the expression of Fas and FLIP in 107 prostate
      adenocarcinoma tissues by immunohistochemistry using a tissue microarray
      approach. Normal glandular cells of the prostates strongly expressed both Fas and
      FLIP proteins. Prostate intraepithelial neoplasm also showed a strong Fas
      immunoreactivity. Fas expression was strongly positive in 60 cancers (56.1%), but
      the remaining 47 cancers showed no (6.5%) or markedly decreased (37.4%) Fas
      immunostaining compared with the normal glandular cells of the same patients. By
      contrast, FLIP expression was strong in most (103/107; 96.3%) of the cancers, and
      only four cancers (3.7%) showed decreased immunoreactivities compared with the
      normal cells. The decreased expression of Fas was not associated with pathologic
      characteristics, including FLIP expression, size of the cancers, age, Gleason
      score and stage. The decreased expression of Fas in a large fraction of prostate
      cancers compared with their normal cells suggested that loss of Fas expression
      might play a role in tumorigenesis in some prostate cancers possibly by
      inhibiting apoptosis mediated by Fas.

PMID- 19161535
TI  - Real-time multiplex PCR assay for detection of Yersinia pestis and Yersinia
      pseudotuberculosis.
AB  - A multiplex real-time polymerase chain reaction (PCR) assay was developed for the
      detection of Yersinia pestis and Yersinia pseudotuberculosis. The assay includes
      four primer pairs, two of which are specific for Y. pestis, one for Y. pestis and
      Y. pseudotuberculosis and one for bacteriophage lambda; the latter was used as an
      internal amplification control. The Y. pestis-specific target genes in the assay
      were ypo2088, a gene coding for a putative methyltransferase, and the pla gene
      coding for the plasminogen activator. In addition, the wzz gene was used as a
      target to specifically identify both Y. pestis and the closely related Y.
      pseudotuberculosis group. The primer and probe sets described for the different
      genes can be used either in single or in multiplex PCR assays because the
      individual probes were designed with different fluorochromes. The assays were
      found to be both sensitive and specific; the lower limit of the detection was 10
      100 fg of extracted Y. pestis or Y. pseudotuberculosis total DNA. The sensitivity
      of the tetraplex assay was determined to be 1 cfu for the ypo2088 and pla probe
      labelled with FAM and JOE fluorescent dyes, respectively.

PMID- 19161536
TI  - Cyclooxygenase-2 expression on urothelial and inflammatory cells of cystoscopic
      biopsies and urine cytology as a possible predictive marker for bladder
      carcinoma.
AB  - Cyclooxygenase-2 (COX-2) is a key inducible enzyme involved in the production of
      prostaglandins. It contributes to human carcinogenesis by various mechanisms. The
      aim of the current study was to elucidate the possible involvement of COX-2 in
      human bladder carcinoma by examining its expression on both urothelial and
      inflammatory cells in tissue biopsies and urine cytology samples of different
      urinary bladder lesions. A total of 65 patients were included in the study and
      were selected from cases admitted to Urology Department, Theodor Bilharz Research
      Institute (TBRI), Giza, Egypt. They represented seven control cases with almost
      normal-looking bladder tissue; pure chronic cystitis (n=12); premalignant lesions
      (18) in the form of squamous metaplasia (n=8) or urothelial dysplasia (n=10) as
      well as transitional cell carcinoma (TCC) (n=18), and squamous cell carcinoma
      (SqCC) (n=10). Immunohistochemistry of formalin-fixed, paraffin-embedded tissue
      sections and urine cytology samples was performed for all cases using COX-2 (H
      62): sc-7951, a rabbit polyclonal antibody. The study revealed positive COX-2
      expression on the urothelial and inflammatory cells of cystoscopic biopsies from
      all cases of pure chronic cystitis, squamous metaplasia and SqCC compared with
      42.8% and 71.4% of normal controls, respectively. The score of urothelial COX-2
      expression was sequentially up-regulated from normal to chronic cystitis (either
      pure or associated with premalignant changes) (p<0.05) to malignant changes
      (p<0.05). However, the inflammatory cellular expression was down-regulated with
      malignant transformation compared with chronic cystitis (p<0.05). In TCC, COX-2
      was over-expressed on both urothelial and inflammatory cells in advanced tumors.
      Urine cytology samples were positive for COX-2 in a comparable manner to that
      observed in cystoscopic biopsies. Accordingly, the results of the current study
      have provided new information in two aspects: First, is the possibility of using
      the differential COX-2 expression on both inflammatory and urothelial cells as
      markers for premalignant or malignant transformation; second, besides cystoscopy,
      urine cytology was found to have a high sensitivity for COX-2 expression and
      hence proved to be valuable in malignancy as a non-invasive substitute for
      cystoscopy.

PMID- 19161537
TI  - Expression of CPEB, GAPDH and U6snRNA in cervical and ovarian tissue during
      cancer development.
AB  - Persistent infection with high-risk human papillomavirus (HPV) and expression of
      the proteins E6 and E7 is a prerequisite for development of cervical cancer. The
      distal non-coding part of E6/E7 messengers from several HPV types is able to
      downregulate synthesis of a reporter gene through mechanisms with involvement of
      cytoplasmic polyadenylation elements (CPEs) in the messengers. We here show that
      the mRNA levels of one of the four known CPE-binding proteins (CPEBs), the CPEB3,
      were downregulated in HPV-positive cervical cancers, whereas in ovarian cancer
      the CPEB1 mRNA level was downregulated. In addition, we showed that the RNA
      levels of the widely used reference marker GAPDH were upregulated in both cancer
      forms, and the level of the reference marker U6snRNA was upregulated in cervical
      cancers. Moreover, a possible correlation between the degree of U6snRNA
      upregulation and cervical cancer propagation was shown. These changes observed in
      CPEB1 and CPEB3 might indicate regulatory functions of CPEBs in cancer
      development of HPV-positive and HPV-negative tumors, respectively, and the
      U6snRNA, GAPDH mRNA and CPEB1 mRNA levels may be useful as tumor markers for
      genital cancers although further investigations are needed.

PMID- 19161538
TI  - C-type natriuretic peptide in prostate cancer.
AB  - C-type natriuretic peptide (CNP) is expressed in the male reproductive organs in
      pigs. To examine whether the human prostate also expresses the CNP gene, we
      measured CNP and N-terminal proCNP in prostate cancer tissue extracts and
      performed immunohistochemical biopsy staining. Additionally, proCNP-derived
      peptides were quantitated in plasma from patients with prostate cancer. Blood was
      collected from healthy controls and patients before surgery for localized
      prostate cancer. Tissue extracts were prepared from tissue biopsies obtained from
      radical prostatectomy surgery. N-terminal proCNP, proCNP (1-50) and CNP were
      measured in plasma and tissue extracts. Biopsies were stained for CNP-22 and N
      terminal proCNP. Tissue extracts from human prostate cancer contained mostly N
      terminal proCNP [median 5.3 pmol/g tissue (range 1.0-12.9)] and less CNP [0.14
      pmol/g tissue (0.01-1.34)]. Immunohistochemistry demonstrated the presence of the
      peptides in prostatic epithelial cells. The N-terminal proCNP concentrations in
      plasma were marginally lower in patients with localized prostate cancer compared
      with control subjects [13.8 pmol/l (11.0-17.2) vs. 15.1 pmol/l (10.4-23.2),
      p=0.002] but not enough to justify the use of N-terminal proCNP as a cancer
      marker. Further research is needed to establish whether measurement of proCNP
      derived peptides may offer clinical information.

PMID- 19161539
TI  - High frequency of false-positive signals in a real-time PCR-based "Plus/Minus"
      assay.
AB  - Molecular biological methods using real-time polymerase chain reaction (RT-PCR)
      for detection of bacterial and viral genes in different environments have been
      developed into assays from different commercial sources. Applied Biosystems
      include and support two applications with their TaqMan instrument: the
      "Plus/Minus" and the "Allelic Discrimination" assays. These approaches are RT-PCR
      based, use short primers and fluorescent-labeled TaqMan probes and include three
      processes: a pre-read run, a PCR-amplification run, and a post-read run. In the
      "Plus/Minus" assay, samples and controls (distilled water) are loaded into the
      instrument, which calculates a positive or a negative outcome based on
      differences in signals between samples and the controls. When testing the
      "Plus/Minus" assay for detection of usp genes encoding a uropathogenic specific
      protein in Escherichia coli, an inordinately high proportion of false-positive
      signals was observed. This was shown to be due to a serious methodological
      deficiency. Our observations indicate that an adequate no-template control
      closely matching the target samples in all aspects, including amount of DNA, is
      required to establish a correct threshold in the pre-read run that forms the
      basis for further calculations in the post-read run of the "Plus/Minus" assay.

PMID- 19161540
TI  - Habitual micronutrient intake during and after pregnancy in Caucasian Londoners.
AB  - Micronutrient status is of fundamental importance both upon conception and
      throughout pregnancy. There is an abundance of literature investigating nutrient
      intakes during individual trimesters of pregnancy but few studies have
      investigated baseline intakes of nutrients throughout gestation as a continuum.
      The current investigation set out to measure habitual micronutrient intakes at
      weeks 13, 25, 35 of pregnancy and 6 weeks postpartum using a prospective
      background information questionnaire, 4-7-day weighed food diary and postnatal
      questionnaire. Seventy-two primiparous, Caucasian Londoners were recruited at the
      study start with 42 completing the first, second, third trimester and postpartum
      study stages respectively. Study findings indicated that sodium intakes were
      significantly higher than UK guidelines throughout and after pregnancy (P <
      0.001). Intakes of folate, iron, vitamin D, potassium, iodine and selenium were
      lower than UK recommendations during and after pregnancy, but to varying levels
      of statistical significance (P < 0.05). Only 23-38% of women met UK
      recommendations for folate (300 microg day(-1)) through dietary sources.
      Similarly, only a small percentage of women met dietary guidelines for iron (19
      28%). The findings from the current study indicate that public health
      interventions may be required to help expectant mothers achieve an optimal diet,
      particularly after birth when dietary recommendations increase for some
      micronutrients.

PMID- 19161541
TI  - Reconfiguring insufficient breast milk as a sociosomatic problem: mothers of
      premature babies using the kangaroo method in Brazil.
AB  - This study focuses on Brazilian mothers who gave birth to premature babies who
      were discharged from hospital using the Kangaroo Mother Care Method. While
      mothers left the hospital breastfeeding exclusively, once back at home, they
      abandoned exclusive breastfeeding because of insufficient breast milk (IBM). In
      this project we explored how IBM was interpreted by mothers within their social
      context. Participatory research using the Creative Sensitive Method was done in
      the homes of mothers with family members and neighbours. We described the
      conflicting social discourse that influenced the mothers' perception of IBM and
      explored their sources of distress. At the hospital and Kangaroo ward, mothers
      considered that clinicians recognized they were experiencing IBM and thus
      supported them to overcome this problem. Back at home and in their community,
      other sources of stress generated anxiety such as: the lack of outpatient
      clinical support, and conflicting local norms to care and feed premature babies.
      These difficulties combined with economic constraints and discontinuity in models
      of health care led mothers to lose confidence in their breastfeeding capacity.
      Mothers, thus, rapidly replaced exclusive breastfeeding by mixed feeding or
      formula feeding. Our analysis suggests that IBM in our sample was the result of a
      socio-somatic process. Recommendations are proposed to help overcome IBM and
      corresponding contextual barriers to exclusive breastfeeding.

PMID- 19161542
TI  - Effect of combined maternal and infant vitamin D supplementation on vitamin D
      status of exclusively breastfed infants.
AB  - Severe vitamin D deficiency in mothers and their breastfed infants is a
      significant health problem in the Middle East. Supplementation of the breastfed
      infant alone with the recommended dose of vitamin D may be insufficient in high
      risk population. We investigated the effect of combined maternal and infant
      vitamin D supplementation on vitamin D status of the breastfed infant. We
      examined also the effect of supplementation on vitamin D antirachitic activity of
      breast milk in a subset of mothers. Healthy breastfeeding mothers (n = 90) were
      randomly assigned to 2000 IU daily (group 1) or 60,000 IU monthly (group 2) of
      vitamin D(2), and all their infants (n = 92) received 400 IU daily of vitamin
      D(2) for 3 months. Most infants had vitamin D deficiency - 25-hydroxyvitamin D
      [25(OH)D] <or= 37.5 nmol L(-1)- at study entry. Serum 25(OH)D concentrations at 3
      months increased significantly from baseline in infants of mothers in group 1
      (13.9 +/- 8.6 vs. 49.6 +/- 18.5 nmol L(-1), P < 0.0001) and group 2 (13.7 +/-
      12.1 vs. 44.6 +/- 15.0 nmol L(-1), P < 0.0001). Maternal and infant serum 25(OH)D
      concentrations correlated positively at baseline (r = 0.36, P = 0.01) and 3
      months (r = 0.46, P = 0.002). Milk antirachitic activity increased from
      undetectable (<20 IU L(-1)) to a median of 50.9 IU L(-1). In conclusion, combined
      maternal and infant vitamin D supplementation was associated with a threefold
      increase in infants' serum 25(OH)D concentrations and a 64% reduction in the
      prevalence of vitamin D deficiency without causing hypervitaminosis D.

PMID- 19161543
TI  - Using programme theory to assess the feasibility of delivering micronutrient
      Sprinkles through a food-assisted maternal and child health and nutrition
      programme in rural Haiti.
AB  - This paper uses programme theory to assess, in the context of an effectiveness
      evaluation, the feasibility and acceptability of distributing micronutrient
      Sprinkles through a food-assisted maternal and child health and nutrition
      programme in rural Haiti. We laid out the steps related to programme delivery and
      household utilization of Sprinkles and used qualitative and quantitative methods
      to gather data on these steps. Methods included structured observations, checks
      of beneficiary ration cards, exit interviews, focus group discussions (FGD),
      individual interviews and survey data from the effectiveness evaluation. Results
      are as follows: (1) information on use of Sprinkles was provided before mothers
      first received them, as planned; (2) Sprinkles were re-packaged and distributed
      as planned and in the appropriate amount; (3) almost all mothers (96%) received
      two monthly rations of Sprinkles and received timely information on their use;
      (4) mothers understood instructions about use of Sprinkles and acceptance was
      high, and no selling of the product was reported or observed; and (5) mothers
      reported using Sprinkles as instructed, every day (63% in survey; 86% at exit
      interviews), and for the child only (99%). FGD with staff highlighted the
      acceptance of the intervention, with a reported 'modest' increase in workload.
      Within this well-established programme, it proved feasible to distribute
      Sprinkles and to ensure appropriate use by beneficiary mothers. Existing
      programme venues were suitable for distributing Sprinkles and educating mothers
      about their use. Use of programme theory helped to assess feasibility and
      acceptability of the Sprinkles intervention and provided useful information for
      programme replication or scale-up.

PMID- 19161544
TI  - Reconsidering childhood undernutrition: can birth spacing make a difference? An
      analysis of the 2002-2003 El Salvador National Family Health Survey.
AB  - It is well understood that undernutrition underpins much of child morbidity and
      mortality in less developed countries, but the causes of undernutrition are
      complex and interrelated, requiring a multipronged approach for intervention.
      This paper uses a subsample of 3853 children under age 5 from the most recent
      family health survey in El Salvador to examine the relationship between birth
      spacing and childhood undernutrition (stunting and underweight). While recent
      research and guidance suggest that birth spacing of three to five years
      contributes to lower levels of infant and childhood mortality, little attention
      has been given to the possibility that short birth intervals have longer-term
      effects on childhood nutrition status. The analysis controls for clustering
      effects arising from siblings being included in the subsample, as well as
      variables that are associated with household resources, household structure,
      reproductive history and outcomes, and household social environment. The results
      of the multiple regression analyses find that in comparison to intervals of 36-59
      months, birth intervals of less than 24 months and intervals of 24-35 months
      significantly increase the odds of stunting (<24 months Odds Ratio (OR) = 1.52;
      95% confidence interval (CI): 1.21-1.92; 25-36 months OR = 1.30; 95% CI: 1.05
      1.64). Other factors related to stunting and underweight include standard of
      living index quintile, child's age, mother's education, low birthweight, use of
      prenatal care, and region of the country where the child lives. Policy and
      program implications include more effective use of health services and outreach
      programs to counsel mothers on family planning, breastfeeding, and well child
      care.

PMID- 19161545
TI  - Maternal autonomy is inversely related to child stunting in Andhra Pradesh,
      India.
AB  - Child stunting, an outcome of chronic undernutrition, contributes to poor quality
      of life, morbidity and mortality. In South Asia, the low status of women is
      thought to be one of the primary determinants of undernutrition across the
      lifespan. Low female status can result in compromised health outcomes for women,
      which in turn are related to lower infant birthweight and may affect the quality
      of infant care and nutrition. Maternal autonomy (defined as a woman's personal
      power in the household and her ability to influence and change her environment)
      is likely an important factor influencing child care and ultimately infant and
      child health outcomes. To examine the relationship between maternal autonomy and
      child stunting in Andhra Pradesh, India, we analysed data from National Family
      Health Survey (NFHS)-2. We used cross-sectional demographic, health and
      anthropometric information for mothers and their oldest child <36 months (n =
      821) from NFHS-2. The main explanatory variables of autonomy are presented by
      four dimensions - decision making, permission to travel, attitude towards
      domestic violence and financial autonomy - constructed using seven binary
      variables. Logistic regression models were used to test associations between
      indicators of female autonomy and the risk of having a stunted child. Women with
      higher autonomy {indicated by access to money [odds ratio (OR) = 0.731; 95%
      confidence interval (CI) 0.546, 0.981] and freedom to choose to go to the market
      [OR = 0.593; 95% CI 0.376, 0.933]} were significantly less likely to have a
      stunted child, after controlling for household socio-economic status and mother's
      education. In this south Indian state, two dimensions of female autonomy have an
      independent effect on child growth, suggesting the need for interventions that
      increase women's financial and physical autonomy.

PMID- 19161546
TI  - Delayed introduction of lumpy foods to children during the complementary feeding
      period affects child's food acceptance and feeding at 7 years of age.
AB  - The study aimed to follow up children who had been introduced to lumpy solids
      (chewy foods) at different ages, and to assess their dietary intake and feeding
      difficulties at seven years of age. Information was collected from a
      geographically defined population of 7821 mothers of children born in 1991/92,
      part of the Avon Longitudinal Study of Parents and Children (ALSPAC). Self-report
      questionnaires were completed by the mother about her child at 6 months, 15
      months, and 7 years postpartum about food foods eaten and feeding difficulties.
      Children were divided into three groups based on the age at which they were first
      introduced to 'lumpy' solids: 12.1% were introduced before 6 months of age, 69.8%
      were introduced between 6 and 9 months of age and 18.1% were introduced after 9
      months. Children introduced to lumpy solids after the age of 9 months ate less of
      many of the food groups at seven years, including all 10 categories of fruit and
      vegetables, than those introduced to lumpy foods between 6-9 months (P < 0.05
      0.001). In addition they were reported as having significantly more feeding
      problems at seven years (P < 0.05-0.001). The long-term feeding problems and
      reduced consumption of important food groups such as fruit and vegetables in
      children who are introduced to lumpy foods after the age of 9 months is a cause
      for concern. Health professionals must encourage the progression from purees and
      exposure to important food groups.

PMID- 19161547
TI  - Relationship between socio-demographic and anthropometric variables and number of
      erupted primary teeth in suburban Nigerian children.
AB  - The socio-demographic and anthropometric variables could influence the number of
      teeth present in the child's mouth. To determine the effect of anthropometric and
      socio-demographic variables on the number of erupted primary teeth, a cross
      sectional study was performed involving 1013 children aged between 4 and 36
      months who attended the immunization clinics in Ile-Ife, Nigeria. Statistical
      analyses were performed using STATA. The analyses included frequencies, cross
      tabulations, chi squared test and t-test. The number of erupted teeth was
      modelled as the dependent variable in a multiple regression (Binomial) model, and
      the socio-demographic (age, gender and socio-economic status) and anthropometric
      variables, such as weight and height at presentation, as predictor variables.
      Statistical significance was inferred at P < 0.05. The age and height at
      presentation had significant association with the number of erupted teeth in this
      study population (P < 0.001). Also children from high socio-economic class in
      relation to low socio-economic class had significant larger number of erupted
      teeth in this study population (P < 0.001). The age and height of the child at
      presentation were significantly related to the number of erupted teeth. Also
      children from high socio-economic class had significant lager number of erupted
      teeth compared with children from low socio-economic class.

PMID- 19161551
TI  - Generation of drug-resistant mutants of Helicobacter pylori in the presence of
      peroxynitrite, a derivative of nitric oxide, at pathophysiological concentration.
AB  - In the present study it has been shown that the reactive nitrogen species,
      peroxynitrite, can cause at least a 7.1-fold increase in the frequency of
      occurrence of drug-resistant mutants of Helicobacter pylori at a
      pathophysiological concentration (e.g. 1.0 microM) and in the presence of CLR.
      Furthermore, the CLR MIC of these resistant H. pylori strains increased by at
      least 250 times or higher in CLR susceptibility. In the 45 resistant strains, the
      modification of 23S rRNA A2142G was the predominant mutation (22/45), followed by
      A2143G (17/45) within the sequences of 23S rRNA. The other mutants were one each
      (1/45) in A2142T, and T2269G, and two each (2/45) in C2695G and T1944C,
      respectively. These results show that the inflammatory host reaction involving
      induction of reactive oxygen species (e.g. O(.-)2), and the inducible form of
      nitric oxide synthase, is a significant cause of mutation via peroxynitrite
      formation, particularly in drug-resistant bacterial strains.

PMID- 19161552
TI  - Fusion protein consisting of the first immunoglobulin-like domain of porcine
      nectin-1 and Fc portion of human IgG1 provides a marked resistance against
      pseudorabies virus infection to transgenic mice.
AB  - Nectin-1 is a Ca2+-independent Ig-like cell-cell adhesion molecule and an
      alphaherpesvirus receptor that binds to virion glycoprotein D by the first Ig
      like domain. We have investigated the antiviral potentials of soluble forms of
      porcine nectin-1 to PRV infection by generating transgenic mice expressing
      different types of fusion protein. Previously, we reported that mice transgenic
      for a chimera that carried the entire ectodomain of porcine nectin-1 fused to the
      Fc portion of porcine IgG1 were more resistant than those transgenic for a
      chimera that carried the first Ig-like domain fused to the Fc portion. Recently,
      we generated transgenic mice expressing a fusion protein made of the first Ig
      like domain fused to the Fc portion of human IgG1, and reported that they showed
      a microphthalmia. Here, two transgenic mouse lines expressing the fusion protein
      were challenged with PRV for comparing their resistances with those of transgenic
      mice expressing different types of fusion protein. Surprisingly, both transgenic
      mouse lines showed a high resistance to the viral infection, especially via the
      i.n. route. Significant resistance of the embryonic fibroblasts was also
      observed. Altogether, these findings indicated that the fusion protein consisting
      of the first Ig-like domain fused to the human Fc portion provided a marked
      resistance against PRV infection to the transgenic mice.

PMID- 19161553
TI  - Genetic stability (in vivo) of the attenuated oral rabies virus vaccine SAD B19.
AB  - The distribution of oral rabies vaccine baits containing replication-competent
      live viruses poses certain environmental safety risks; among others, the
      possibility of reversion to or an increase in virulence. Hence, the genetic
      stability of the complete genome of the most widely used oral rabies vaccine
      virus, SAD B19, was examined after four and 10 serial i.c. passages in foxes and
      mice, respectively. It was shown that the consensus strain of SAD B19 was
      extremely stable in vivo. After 10 consecutive passages in mice not a single
      mutation was observed. In foxes, seven single nucleotide exchanges were found
      between the first and fourth passage, of which only one resulted in an amino acid
      exchange at position 9240 of the L-gene. This mutation was not observed during
      the first three passages and, furthermore, it was shown that this mutation was
      not linked to enhanced virulence.

PMID- 19161554
TI  - Multiplex real-time PCR for the simultaneous detection of herpes simplex virus,
      human herpesvirus 6, and human herpesvirus 7.
AB  - A simultaneous detection system to quantify HSV, HHV-6, and HHV-7 DNA via
      multiplex real-time PCR using different fluorochromes was developed. The minimum
      quantitative level established via this multiplex assay was four copies per
      reaction for HSV type 1, four copies for HHV-6, and three copies for HHV-7,
      respectively. The dynamic range encompassed at least six orders of magnitude. The
      system was specific and reproducible even in the presence of large amounts of
      other viral DNA. We then applied this multiplex real-time PCR assay to 105 CSF
      specimens obtained from subjects less than 15 years old in whom a diagnosis of
      viral encephalitis/encephalopathy was suspected on clinical grounds. The
      detection rate for each viral DNA was 6.7% for HSV, 9.5% for HHV-6, and 1.9% for
      HHV-7. These results indicate that our system is reliable and may be useful for
      the rapid diagnosis of viral encephalitis/encephalopathy.

PMID- 19161555
TI  - IL-4-dependent induction of IgE basophils in peripheral blood and IgE B cells in
      spleen as respective indicators of allergen sensitization and a precursor of
      cells secreting allergen-specific IgE antibody.
AB  - It was recently reported by us that either primary i.n. or i.p. injection of
      cedar pollen extract into BALB/c mice, or a second s.c. injection of the allergen
      into i.v. or s.c. sensitized mice, causes an IL-4-dependent increase in total IgE
      serum antibody to produce allergen-specific IgE antibody upon further s.c.
      sensitization. To determine the biology of total IgE antibody, in the present
      study IgE+ cells in peripheral blood or lymphoid tissues of allergen-sensitized
      BALB/c mice have been characterized. In peripheral blood, mice sensitized one to
      three times with the allergen produced a 2.5- to 4-fold increase in the number of
      IgE+ cells, with a time-course similar to that of the concentration of total IgE
      antibody in serum. These IgE+ cells were basophils. On the other hand, the number
      of IgE+ cells in the lymphoid tissues did not change significantly after an i.n.,
      i.p., i.v. or s.c. injection of allergen into the mice, whereas a second s.c.
      injection of the allergen into the i.v.-, but not into the i.n.-, i.p.- or s.c.-,
      sensitized mice induced a small number of IgE+/IgM+/B220+ B cells in the spleen.
      In contrast, IgE+ cells were not seen in the blood or spleen of IL-4 -/- mice
      after sensitization with the allergen. These results suggest that IgE+ basophils
      in the peripheral blood, and IgE+ B cells in the spleen, might be IL-4
      dependently induced as an indicator of sensitization with allergen, and a
      precursor of cells secreting allergen-specific IgE antibody, respectively.

PMID- 19161556
TI  - Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear
      canal of an inpatient in a Japanese hospital.
AB  - A single strain of a novel ascomycetous yeast species belonging to the genus
      Candida was isolated from the external ear canal of an inpatient in a Japanese
      hospital. Analyses of the 26S rDNA D1/D2 domain, nuclear ribosomal DNA ITS region
      sequences, and chemotaxonomic studies indicated that this strain represents a new
      species with a close phylogenetic relationship to Candida ruelliae and Candida
      haemulonii in the Metschnikowiaceae clade. This strain grew well at 40 degrees C,
      but showed slow and weak growth at 42 degrees C. The taxonomic description of
      Candida auris sp. nov. is proposed (type strain JCM15448T= CBS10913T= DSM21092T).

PMID- 19161557
TI  - Simple broad-spectrum protocol using labiase for bacterial cell lysis to prepare
      genomic DNA for pulsed-field gel electrophoresis analysis.
AB  - We have developed a simple broad-spectrum protocol using labiase for bacterial
      cell lysis in pulsed-field gel electrophoresis analysis. The protocol reported
      here is widely applicable to the preparations of genomic DNA from Gram-negative
      and -positive pathogens, including enterococcal strains resistant to any
      conventional lysis protocols.

PMID- 19161558
TI  - Self-assembly of sapovirus recombinant virus-like particles from polyprotein in
      mammalian cells.
AB  - The SaV genome is a positive-sense, non-segmented single-strand RNA molecule of
      approximately 7.5 kb that is polyadenylated at its 3' terminus. The major capsid
      (VP1) of SaV is thought to be produced as the ORF1 polyprotein followed by
      cleavage, or translation from subgenomic RNA (3'-coterminal with the virus
      genome), or both. We have recently reported the formation of SaV VLP from
      subgenomic-like RNA in mammalian cells. In the present study, we demonstrated
      that the VP1 cleaved from a part of ORF1 polyprotein self-assembled into VLP in
      mammalian cells when a transient expression system using a recombinant vaccinia
      virus encoding T7 RNA polymerase was used.

PMID- 19161559
TI  - Non-human primate surrogate model of hepatitis C virus infection.
AB  - More than 170 million people worldwide are chronically infected by HCV, which is
      the causative agent of chronic hepatitis C, cirrhosis, and finally liver cancer.
      Although animal models of viral hepatitis are a prerequisite for the evaluation
      of antiviral and vaccine efficacy, the restricted host range of HCV has hampered
      the development of a suitable small animal model of HCV infection. Use of the
      chimpanzee, the only animal known to be susceptible to HCV infection, is limited
      by ethical and financial restrictions. In this regard GBV-B, being closely
      related to HCV, appears to be a promising non-human surrogate model for the study
      of HCV infection. This review describes the characteristic of GBV-B infection of
      New World monkeys, and discusses current issues concerning the GBV-B model and
      its future directions.

PMID- 19161561
TI  - 10 years of rizatriptan.

PMID- 19161562
TI  - Migraine in the triptan era: lessons from epidemiology, pathophysiology, and
      clinical science.
AB  - The triptan era has been a time of remarkable progress for migraine diagnosis and
      treatment. In this paper, we review some of the advances achieved in migraine
      science during this era focusing on 3 themes: lessons from clinical practice,
      lessons from epidemiology and lessons from pathophysiology. Science has shown
      that migraine is a disorder of the brain, and that the key events happen in the
      the trigeminal neuronal pathways, not on blood vessels. Clinical science has led
      to the observation that migraine sometimes progresses or remits. This in turn led
      to longitudinal epidemiologic studies focusing on factors that determine migraine
      prognosis. In addition, these studies raised questions about the mechanisms of
      migraine progression, including the role of allodynia, obesity, inflammation, and
      medications as determinants of progression. This in turn opens a new set of
      scientific questions about the neurobiologic determinants of migraine, as well as
      of its clinical course, and exciting opportunities to develop new therapies for
      this highly disabling brain disorder.

PMID- 19161564
TI  - Acute migraine treatment with rizatriptan in real world settings - focusing on
      treatment strategy, effectiveness, and behavior.
AB  - Although randomized controlled trials (RCTs) are the gold standard for assessing
      efficacy of a drug intervention, because they are conducted in a highly selected
      group of patients, they do not necessarily reflect normal customary or optimized
      patient care. Accordingly, information from RCTs must be supplemented by outcomes
      research and by nonexperimental or quasi-experimental study designs. Herein, we
      discuss information that supplements the rigorous but sometimes rigid nature of
      RCTs in an effort to better understand the clinical utility of drug treatment for
      migraine with patient-centered outcomes in mind. We start by discussing several
      lessons we learned from RCTs on comparative triptan studies, followed by
      presenting data on outcomes studies for rizatriptan. We then briefly discuss
      migraine treatment behavior issues, including early treatment and adherence to
      treatment.

PMID- 19161563
TI  - Ten years of rizatriptan: from development to clinical science and future
      directions.
AB  - The year 2008 marked the 10th anniversary since rizatriptan was first launched
      for the acute treatment of migraine. In this article we discuss the concepts that
      motivated the preclinical and clinical development of rizatriptan, the clinical
      evidence that has driven its use over the past decade, rizatriptan's overall
      contribution to the field, and future directions for research.

PMID- 19161565
TI  - Moving forward - essential questions for the next 10 years.
AB  - The future is bright for migraine sufferers. For acute treatment, CGRP
      antagonists and combination products will provide more complete, longer lasting,
      and safer relief. "Designer drugs" for migraine prevention will be identified
      based on their ability to block cortical spreading depression and will improve
      migraine treatment. Genetic and environmental risk factors that promote migraine
      progression will be identified and preventing progression will become a standard
      goal in treatment. Some of the devices intended to treat migraine will be
      approved and will provide important options for sufferers seeking to avoid drugs.
      Clinical trials that evaluate behavioral and pharmacologic interventions and
      their impact on patient centered outcomes will emerge. The emergence of novel
      treatments, when coupled with strategies for individualizing and optimizing
      treatment while maximizing adherence, will result in ever improving patient
      outcomes.

PMID- 19161566
TI  - When the discharge plan is deportation: hospitals, immigrants, and social
      responsibility.

PMID- 19161567
TI  - Human nature and enhancement.
AB  - Appeals to the idea of human nature are frequent in the voluminous literature on
      the ethics of enhancing human beings through biotechnology. Two chief concerns
      about the impact of enhancements on human nature have been voiced. The first is
      that enhancement may alter or destroy human nature. The second is that if
      enhancement alters or destroys human nature, this will undercut our ability to
      ascertain the good because, for us, the good is determined by our nature. The
      first concern assumes that altering or destroying human nature is in itself a bad
      thing. The second concern assumes that human nature provides a standard without
      which we cannot make coherent, defensible judgments about what is good. I will
      argue (1) that there is nothing wrong, per se, with altering or destroying human
      nature, because, on a plausible understanding of what human nature is, it
      contains bad as well as good characteristics and there is no reason to believe
      that eliminating some of the bad would so imperil the good as to make the
      elimination of the bad impermissible, and (2) that altering or destroying human
      nature need not result in the loss of our ability to make judgments about the
      good, because we possess a conception of the good by which we can and do evaluate
      human nature. I will argue that appeals to human nature tend to obscure rather
      than illuminate the debate over the ethics of enhancement and can be eliminated
      in favor of more cogent considerations.

PMID- 19161569
TI  - Publishing your dissertation.

PMID- 19161568
TI  - Clarifying appeals to dignity in medical ethics from an historical perspective.
AB  - Over the past few decades the concept of (human) dignity has deeply pervaded
      medical ethics. Appeals to dignity, however, are often unclear. As a result some
      prefer to eliminate the concept from medical ethics, whereas others try to render
      it useful in this context. We think that appeals to dignity in medical ethics can
      be clarified by considering the concept from an historical perspective. Firstly,
      on the basis of historical texts we propose a framework for defining the concept
      in medical debates. The framework shows that dignity can occur in a relational,
      an unconditional, a subjective and a Kantian form. Interestingly, all forms
      relate to one concept since they have four features in common: dignity refers, in
      a restricted sense, to the 'special status of human beings'; it is based on
      essential human characteristics; the subject of dignity should live up to it; and
      it is a vulnerable concept, it can be lost or violated. We argue that being
      explicit about the meaning of dignity will prevent dignity from becoming a
      conversation-stopper in moral debate. Secondly, an historical perspective on
      dignity shows that it is not yet time to dispose of dignity in medical ethics. At
      least Kantian and relational dignity can be made useful in medical ethics.

PMID- 19161570
TI  - Development of a clinical practice guideline for testing nasogastric tube
      placement.
AB  - PURPOSE: A Perth metropolitan hospital group standardized changes to nasogastric
      tube placement, including removal of the "whoosh test" and litmus paper, and
      introduction of pH testing. DESIGN AND METHODS: Two audits were conducted:
      bedside data collection at a pediatric hospital and a point-prevalence audit
      across seven hospitals. RESULTS: Aspirate was obtained for 97% of all tests and
      pH was < or = 5.5 for 84%, validating the practice changes. However, patients on
      continuous feeds and/or receiving acid-inhibiting medications had multiple pH
      testing fails. PRACTICE IMPLICATIONS: Nasogastric tube placement continues to
      present a challenge for those high-risk patients on continuous feeds and/or
      receiving acid-inhibiting medications.

PMID- 19161571
TI  - Exploring youth development with diverse children: correlates of risk, health,
      and thriving behaviors.
AB  - PURPOSE: This study explored the relationships between internal and external
      assets, risk behaviors, health behaviors, and thriving behaviors in diverse
      children. DESIGN AND METHODS: The strength of relationships existing between
      measures, differences between group means based on gender, grades earned, and
      school, and confidence interval (p < or = .05) were tested in a sample of 61
      urban sixth graders. RESULTS: Few assets were related to substance use. Assets
      were related to delinquency acts, health behaviors, and thriving indicators.
      Group differences between schools and gender and the total number of assets were
      noted. PRACTICE IMPLICATIONS: Supporting assets are important to consider when
      nurses perform assessments and design interventions to support youths in their
      maturation processes.

PMID- 19161572
TI  - The Humpty Dumpty Falls Scale: a case-control study.
AB  - PURPOSE: The purpose of this descriptive study was to assess whether the Humpty
      Dumpty Falls Scale (HDFS) identifies hospitalized pediatric patients at high risk
      for falls. DESIGN AND METHODS: The study was a matched case-control design. A
      chart review of 153 pediatric cases who fell and 153 controls who did not fall
      were pair-matched by age, gender, and diagnosis. RESULTS: High-risk patients fell
      almost twice as often as low-risk patients (odds ratio 1.87, confidence interval
      = 1.01, 3.53, p = .03). PRACTICE IMPLICATIONS: A Falls Prevention Pediatric
      Program with the HDFS tool addresses the Joint Commission Patient Safety Goals,
      but further research is needed to examine HDFS sensitivity-specificity.

PMID- 19161573
TI  - Maternal predictors of toddler health status.
AB  - PURPOSE: The purposes of this study were to examine the relationships among
      maternal and environmental variables in the first 6 months postpartum and toddler
      health status, and to identify predictors of toddler health. DESIGN AND METHODS:
      A secondary analysis was conducted on an existing dataset of a longitudinal
      parent-child survey. RESULTS: Maternal stress predicted 8% of the variance in
      child health status at 18 months of age. Children in nonparental care more than
      20 hr per week were perceived as less healthy. PRACTICE IMPLICATIONS: Pediatric
      nurses should assess levels of maternal stress in the early months postpartum and
      anticipate poorer health status in toddlers who spend more than 20 hr per week in
      nonparental care.

PMID- 19161574
TI  - A novel, intensive home-visiting intervention for runaway, sexually exploited
      girls.
AB  - PURPOSE: Few studies have examined interventions that help adolescents who run
      away. This study both describes a home-visiting intervention program for young,
      sexually assaulted runaways (10-14 years old) and provides preliminary outcomes
      from the first 20 female participants. DESIGN AND METHODS: Using a strengths
      based approach, advanced practice nurses provided frequent home and school visits
      and case management, and assisted girls to access an empowerment group over a 1
      year period. RESULTS: Teens' risk behaviors decreased, including truancy, runaway
      episodes, sexually transmitted infections, and substance use. CONCLUSIONS:
      Preliminary results suggest that this is an effective intervention for reducing
      risk behaviors and helping younger runaways reconnect to school and family.
      PRACTICE IMPLICATIONS: Client-centered interventions in community settings can
      address the complex health needs of vulnerable young runaways.

PMID- 19161576
TI  - The relationship of household routines to morbidity outcomes in childhood asthma.
AB  - PURPOSE: The major purpose of this study was to explore the effect of routines on
      asthma management and morbidity outcomes for children with asthma and their
      parents. DESIGN AND METHODS: This study is a secondary data analysis in a sample
      of 150 children, which was originally used for an intervention study. RESULTS:
      Parents who had fewer routines in their homes had lower quality-of-life scores
      and higher burden of asthma scores when compared to parents in households with
      more routines. More routines were associated with improved asthma morbidity
      outcomes as measured by nurse rankings of routines. PRACTICE IMPLICATIONS:
      Assisting families to establish routines may result in improved asthma morbidity
      outcomes.

PMID- 19161575
TI  - Comparing parents' and children's views of children's quality of life after heart
      transplant.
AB  - PURPOSE: The purpose of this focused ethnographic study was to explore the
      quality of life (QOL) of school-age heart-transplant recipients. DESIGN AND
      METHODS: Semistructured interviews were conducted with 11 parent-child dyads.
      Data were analyzed using content analysis and constant comparison. RESULTS:
      Participants identified key factors impacting the children's QOL including:
      participation in normal activities, normalcy, staying healthy, sources of
      strength and support, and struggles (parents' perspectives) and doing what kids
      do, being with family and friends, and being a heart transplant kid (children's
      perspectives). PRACTICE IMPLICATIONS: Interventions focusing on the key factors
      identified by participants may impact the QOL of school-age heart-transplant
      recipients.

PMID- 19161577
TI  - Scientific inquiry. Study designs for program evaluation: how do we know what
      works?

PMID- 19161578
TI  - Ask the expert. Children and nature-deficit disorder.

PMID- 19161580
TI  - What's wrong with these people? clinicians' views of clinical couples.
AB  - Marriage and family therapy (MFT) faculty and graduate students rated the
      "typical" or predictable behaviors of husbands or wives coming for therapy using
      the Georgia Marriage Q-sort. Scores were compared with previously published
      scores for both "ideal" couples (i.e., showing positive behaviors, attitudes, and
      problem-solving skills) and a sample of 136 nonclinical, community couples. A
      review of correlations between MFT raters' scores for clients and the scores for
      "ideal" or actual community husbands or wives indicated that clinicians have
      negative views of both clinical husbands and wives. Such negative views of
      clinical husbands and wives are particularly marked in scores by MFT faculty. MFT
      students had a similarly negative view of clinical husbands, but such views were
      not evident for clinical wives. Recommendations for MFT training and implications
      for future research are discussed.

PMID- 19161581
TI  - Marital therapy, retreats, and books: the who, what, when, and why of
      relationship help-seeking.
AB  - When doubts creep in and marriages begin to falter, where do couples turn for
      assistance? In a longitudinal study of 213 couples over the first 5 years of
      marriage, results indicated relationship help-seeking was relatively common, with
      36% of couples seeking some form of outside help during this period. Individual
      and relationship difficulties predicted increased use of relationship books and
      marital therapy in the following year; therefore, these behaviors appear to be
      important outlets for relationship assistance. In contrast, attending marriage
      retreats/workshops was related only to demographic variables. Results of the
      present study suggest that the most common types of relationship help-seeking by
      community couples are understudied and likely underutilized in the dissemination
      of empirically based marital interventions.

PMID- 19161582
TI  - Divorce is a part of my life... resilience, survival, and vulnerability: young
      adults' perception of the implications of parental divorce.
AB  - A qualitative study among 22 young adults (20-25 years old) whose parents
      divorced during their childhood was conducted in Israel, using semi-structured,
      in-depth, open-ended interviews. Qualitative data analysis led to identification
      of three profiles, aiming at a grounded theoretical conceptualization. Three core
      themes were identified: the centrality of the family; short- and long-term
      implications of parental divorce and its relations to supportive coping
      resources; and perspective at young adulthood. Further analysis led to typifying
      participants by three profiles, which represent the grounded theoretical
      conceptualizations: resilience, survival, and vulnerability. The most prominent
      difference among the profiles was the relationships between participants and
      their parents, and their perception of ongoing parental responsibility. A
      thorough discussion of the results and their implications for future research,
      theory development, and practice are presented.

PMID- 19161583
TI  - Domestic violence assessment procedures among couple therapists.
AB  - Guidelines for addressing domestic violence (DV) in couple therapy have been
      published, but reports of whether therapists routinely follow these suggestions
      are few. A national survey of 620 couple therapists randomly selected from
      American Association for Marriage and Family Therapy members was conducted in
      2000 to assess therapists' strategies for assessing DV and selecting a treatment
      modality when violence is discovered. Less than 4% of respondents indicated
      consistently following key published guidelines for DV screening (universal
      screening using separate interviews and questionnaires). A minority indicated
      that they consider the victim's safety as a factor in treatment modality
      selection. DV may be under-identified by couple therapists and therapists may be
      using conjoint therapy with couples for whom such therapy is contraindicated
      because of relationship violence.

PMID- 19161584
TI  - Differentiation of the self and posttraumatic symptomatology among ex-POWs and
      their wives.
AB  - War captivity is a highly traumatic experience which sometimes has deleterious
      effects on both ex-POWs and their wives. This study examined the relationships
      between posttraumatic stress disorder (PTSD) symptoms and differentiation among
      male ex-prisoners of war (ex-POWs; n = 103), their wives (n = 82), and comparable
      controls. Results show that ex-POWs and their wives endorsed more PTSD symptoms
      than controls. Ex-POWs endorsed more cut-off and fusion than controls, while
      their wives endorsed only more fusion than control wives. Finally, the
      relationship between differentiation and PTSD was found to be stronger among ex
      POW couples than among control couples. The unique characteristics of war
      captivity and the relationships between avoidance symptoms and cut-off were
      suggested as possible explanations.

PMID- 19161585
TI  - The social context of marital happiness in urban Indian couples: interplay of
      intimacy and conflict.
AB  - This research examines the happiness of 182 married, urban Hindu husbands and
      wives. Prior research emphasizes that the processes mediating well-being diverge
      across cultures with personal desires not impacting the happiness of non-Western
      couples. However, with globalization as self needs become important, barometers
      of happiness such as intimacy and conflict in a relationship assume a critical
      role in the quality and longevity of marriage, even for non-Western marriages in
      a contemporary India. Participants were 91 Indian couples, married an average of
      11 years, from three socioeconomic classes, three family structures, and arranged
      and love marriages. Results reveal that happy couples, compared with unhappy
      couples, reported agreement, empathy, validation, support, and fulfilled
      expectations. Couples' experience and expression of intimacy, affected by social
      context, also predicted enhanced levels of happiness in marriage while conflict
      had a negative effect on marital happiness. This research suggests how personal
      desires may be transforming cultural practices.

PMID- 19161586
TI  - The cultural context model: how does it facilitate couples' therapeutic change?
AB  - This study examines how therapeutic change in couples is facilitated in the
      Cultural Context Model based on the model's identified family processes: critical
      consciousness, empowerment, and accountability. Participants included four female
      therapists and three couples who sought treatment voluntarily, two heterosexual
      couples, and one lesbian couple with diverse class and ethnic backgrounds who had
      spent at least 12 months receiving services at the Institute for Family Services
      and who were compliant with treatment. Videotaped sessions were analyzed by
      coding descriptive data using a constant comparative analysis method. An analysis
      of therapeutic interventions and clients' changes showed that the model works in
      four realms: conversational, behavioral, ritual, and community building.

PMID- 19161587
TI  - Spirituality and relationship: a holistic analysis of how couples cope with
      diabetes.
AB  - This study explores how couples' spirituality and relationship processes
      holistically interact to inform diabetes management. Qualitative analysis of
      interviews with 20 heterosexual couples identified five spiritual coping styles
      based on the spiritual meaning they ascribed to the situation and the nature of
      their relationships with God and each other: (a) opportunists approach the
      illness as an opportunity for growth; (b) mutual problem solvers collaborate with
      their partners to respond to their disease; (c) individualistic problem solvers
      take personal responsibility for managing their disease; (d) accepters endure
      their disease; and (e) victims take a hopeless, discouraged approach. Results
      suggest that spirituality and couple communication and problem-solving patterns
      appear intertwined and integral to the practice of family therapy.

PMID- 19161588
TI  - Facilitated disclosure versus clinical accommodation of infidelity secrets: an
      early pivot point in couple therapy. Part 1: couple relationship ethics,
      pragmatics, and attachment.
AB  - A critical and potentially polarizing decision in treating infidelity is whether
      facilitating partner disclosure or accommodating nondisclosure is most beneficial
      following private disclosure of infidelity to the therapist. Given couple
      distress and volatility following disclosure, understandably some therapists
      judge accommodating an infidelity secret both efficient and compassionate.
      Employing Western ethics and an attachment/intimacy lens, we consider ethical,
      pragmatic, and attachment intimacy implications of accommodating infidelity
      secrets. Issues bearing on the decision to facilitate disclosure or accommodate
      nondisclosure include (a) relationship ethics and pragmatics; (b) attachment and
      intimacy consequences; and (c) prospects for healing. We conclude that
      facilitating voluntary disclosure of infidelity, although difficult and
      demanding, represents the most ethical action with the best prospects for renewed
      and vital attachment intimacy.

PMID- 19161590
TI  - Glandular fever and pulmonary artery thrombosis in a paraplegic patient, who had
      undergone splenectomy for splenic trauma sustained along with spinal cord injury:
      misdiagnosed initially as urine infection and later as lymphoma when CT scan
      revealed enlarged lymph nodes: a case report.
AB  - BACKGROUND: A 36-year-old male sustained fracture of first lumbar vertebra,
      splenic tear and paraplegia in a motorcycle accident in 2001; splenectomy was
      performed. CASE PRESENTATION: In 2008, he presented with temperature and feeling
      rough. With a diagnosis of urine infection, he was prescribed ciprofloxacin,
      followed by trimethoprim, amoxicillin, and gentamicin, as temperature did not
      subside. White cell count was 21.2 x 109/L; lymphocytes were 13.05 x 109/L (1.00 
      4.00). Therefore, computerised tomography (CT) of chest and abdomen was
      performed. Thrombus was present in pulmonary arteries bilaterally involving the
      lobar and segmental branches. Enlarged lymph nodes were seen in axillae, chest,
      abdomen and inguinal regions. Radiological diagnosis was lymphoma. Cell marker
      showed an excess of large granular lymphocytes and activated lymphocytes. The
      Glandular Fever Slide Test was positive. Subsequently, Paul Bunnell test was also
      positive. Epstein Barr virus serology was consistent with recent Epstein Barr
      virus infection. Antibiotic was omitted; enoxaparin was prescribed for pulmonary
      artery thrombosis. CONCLUSION: Learning points from this case: (1) Although
      routine administration of antibiotic to a spinal cord injury patient with pyrexia
      may be acceptable in outpatient setting, other possibilities such as infection by
      multi-drug resistant organism, viral infection, venous or, arterial thrombosis
      should be considered if a patient does not respond promptly to antibacterial
      therapy. (2) When full blood count showed lymphocytosis (comprising > 50% of
      white blood cells) with atypical morphology, lymphocyte surface markers, Paul
      Bunnell test, and Epstein Barr virus serology should be performed. These tests
      would have led to a diagnosis of infectious mononucleosis, and abdominal imaging
      studies could have been avoided. (3) Lymphoid hyperplasia is the hallmark of
      infectious mononucleosis; therefore, we should have suspected glandular fever
      rather than lymphoma when CT scan revealed enlarged lymph nodes in abdomen,
      mediastinum, axillae and inguinal regions in this patient, who had lymphocytosis
      with atypical morphology. (4) A soft tissue mass, situated inferior to left
      hemidiaphragm in this asplenic patient, was misinterpreted as lymph nodes; review
      of CT led to the correct diagnosis of splenunculus. (5) Acute infection with
      Epstein Barr virus may lead to transient induction of anti-phospholipid
      antibodies, which can cause vascular thrombosis. (6) This case illustrates the
      value of reviewing test results and discussion with senior doctors, as these
      measures help to recognize medical errors and improve patient care.

PMID- 19161591
TI  - MUTYH Gln324His gene polymorphism and genetic susceptibility for lung cancer in a
      Japanese population.
AB  - BACKGROUND: Genetic polymorphisms of DNA repair enzymes in the base excision
      repair (BER) pathway, may lead to genetic instability and lung cancer
      carcinogenesis. We investigated the interactions among the gene polymorphisms in
      DNA repair genes and lung cancer. METHODS: We analyzed associations among OGG1
      Ser326Cys and MUTYH Gln324His gene polymorphisms in relation to lung cancer risk
      using PCR-RFLP. The study involved 108 lung cancer patients and 121 non-cancer
      controls divided into non-smokers, smokers according to pack-years smoked in
      Japanese. RESULTS: The results showed that the MUTYH His/His genotype compared
      with Gln/Gln genotype showed an increased risk for lung cancer (adjusted odds
      ratio [OR] 3.03, confidence interval [95%CI], 1.31-7.00, p = 0.010), whereas
      there was no significant increase for the Gln/His genotype (adjusted OR 1.35,
      95%CI 0.70-2.61, p = 0.376). The MUTYH His/His genotype was at a borderline
      increased risk for both adenocarcinoma and squamous cell carcinoma (adjusted OR
      2.50, 95%CI 0.95-6.62, p = 0.065 for adenocarcinoma; adjusted OR 3.20, 95%CI 0.89
      11.49, p = 0.075 for squamous cell carcinoma, respectively). However, the OGG1
      Ser/Cys or Cys/Cys genotypes compared with the Ser/Ser genotype did not have
      significantly increased risk for lung cancer, containing either adenocarcinoma or
      squamous cell carcinoma. The joint effect of tobacco exposure and the MUTYH
      His/His genotype compared with the Gln/Gln genotype showed a significant
      association with lung cancer risk in smokers, and there was not significantly
      increased in non-smokers (adjusted OR 3.82, 95%CI 1.22-12.00, p = 0.022 for
      smokers; adjusted OR 2.60, 95%CI 0.60-11.25, p = 0.200 for non-smokers,
      respectively). The effect of tobacco exposure and the OGG1 Ser326Cys showed also
      no significant risk for lung cancer. CONCLUSION: Our findings suggest that the
      MUTYH Gln324His polymorphism appear to play an important role in modifying the
      risk for lung cancer in the Japanese population.

PMID- 19161592
TI  - Behavioral changes of patients after orthognathic surgery develop on the basis of
      the loss of vomeronasal organ: a hypothesis.
AB  - We introduce a hypothesis which presumes that damage to the vomeronasal organ
      during a Le Fort I osteotomy of the maxilla for the purpose of orthognathic
      surgical treatment of congenital or acquired jaw deformities affects the
      patient's social life in terms of the selection of mates and establishment of
      relationships. The vomeronasal organ is chemosensory for pheromones, and thus
      registers unconscious olfactory information which might subsequently act on the
      limbic system of an individual and influence the selection of mates. We believe
      it is connected to an inhibitory feedback mechanism which is responsible for the
      exclusion of inappropriate mates. When the vomeronasal organ is removed or
      damaged during a maxillary osteotomy, the inhibitory function is lost, the
      patient loses the involuntary ability to exclude inappropriate mates, may become
      less committed to an existing mate, or even become promiscuous.

PMID- 19161593
TI  - International observatory on mental health systems: a mental health research and
      development network.
AB  - BACKGROUND: While the mental health situation for most people in low and middle
      income countries is unsatisfactory, there is a renewed commitment to focus
      attention on the mental health of populations and on the scaling up of mental
      health services that have the capacity to respond to mental health service needs.
      There is general agreement that scaling up activities must be evidence-based and
      that the effectiveness of such activities must be evaluated. If these
      requirements are to be realised it will be essential to strengthen capacity in
      countries to conduct rigorous monitoring and evaluation of system development
      projects and to demonstrate sustained benefit to populations. THE OBSERVATORY:
      The International Observatory on Mental Health Systems (IOMHS) will build
      capacity to measure and to track mental health system performance in
      participating countries at national and sub-national (provincial and district)
      levels. The work of IOMHS will depend on the establishment of robust partnerships
      among the key stakeholder groups. The Observatory will build the capability of
      partner organisations and networks to provide evidence-based advice to policy
      makers, service planners and implementers, and will monitor the progress of
      mental health service scaling up activities. SUMMARY: The International
      Observatory on Mental Health Systems will be a mental health research and
      development network that will monitor and evaluate mental health system
      performance in low and middle-income countries.

PMID- 19161594
TI  - Pancreatic islet expression profiling in diabetes-prone C57BLKS/J mice reveals
      transcriptional differences contributed by DBA loci, including Plagl1 and Nnt.
AB  - BACKGROUND: C57BLKS/J (BLKS) mice are susceptible to islet exhaustion in insulin
      resistant states as compared with C57BL6/J (B6) mice, as observed by the presence
      of the leptin receptor (Lepr) allele, Leprdb/db. Furthermore, DBA2/J (DBA) mice
      are also susceptible to beta-cell failure and share 25% of their genome with
      BLKS; thus the DBA genome may contribute to beta-cell dysfunction in BLKS mice.
      RESULTS: Here we show that BLKS mice exhibit elevated insulin secretion, as
      evidenced by improved glucose tolerance and increased islet insulin secretion
      compared with B6 mice, and describe interstrain transcriptional differences in
      glucose response. Transcriptional differences between BLKS and B6 mice were
      identified by expression profiling of isolated islets from both strains. Genomic
      mapping of gene expression differences demonstrated a significant association of
      expression differences with DBA loci in BLKS mice (P = 4x10-27). CONCLUSION: Two
      genes, Nicotinamide nucleotide transhydrogenase (Nnt) and Pleiomorphic adenoma
      gene like 1 (Plagl1), were 4 and 7.2-fold higher respectively in BLKS islets, and
      may be major contributors to increased insulin secretion by BLKS islets. Contrary
      to reports for B6 mice, BLKS mice do not harbor a mutant Nnt gene. We detected 16
      synonymous polymorphisms and a two-amino acid deletion in the Plagl1 gene in BLKS
      mice. Several inflammatory glucose-responsive genes are expressed at a higher
      level in BLKS, suggesting an inflammatory component to BLKS islet dysfunction.
      This study describes physiological differences between BLKS and B6 mice, and
      provides evidence for a causative role of the DBA genome in beta-cell dysfunction
      in BLKS mice.

PMID- 19161595
TI  - The vaginal microflora in relation to gingivitis.
AB  - BACKGROUND: Gingivitis has been linked to adverse pregnancy outcome (APO).
      Bacterial vaginosis (BV) has been associated with APO. We assessed if bacterial
      counts in BV is associated with gingivitis suggesting a systemic infectious
      susceptibilty. METHODS: Vaginal samples were collected from 180 women (mean age
      29.4 years, SD +/- 6.8, range: 18 to 46), and at least six months after delivery,
      and assessed by semi-quantitative DNA-DNA checkerboard hybridization assay (74
      bacterial species). BV was defined by Gram stain (Nugent criteria). Gingivitis
      was defined as bleeding on probing at >or= 20% of tooth sites. RESULTS: A Nugent
      score of 0-3 (normal vaginal microflora) was found in 83 women (46.1%), and a
      score of > 7 (BV) in 49 women (27.2%). Gingivitis was diagnosed in 114 women
      (63.3%). Women with a diagnosis of BV were more likely to have gingivitis (p =
      0.01). Independent of gingival conditions, vaginal bacterial counts were higher
      (p < 0.001) for 38/74 species in BV+ in comparison to BV- women. Counts of four
      lactobacilli species were higher in BV- women (p < 0.001). Independent of BV
      diagnosis, women with gingivitis had higher counts of Prevotella bivia (p <
      0.001), and Prevotella disiens (p < 0.001). P. bivia, P. disiens, M. curtisii and
      M. mulieris (all at the p < 0.01 level) were found at higher levels in the BV+/G+
      group than in the BV+/G- group. The sum of bacterial load (74 species) was higher
      in the BV+/G+ group than in the BV+/G- group (p < 0.05). The highest odds ratio
      for the presence of bacteria in vaginal samples (> 1.0 x 104 cells) and a
      diagnosis of gingivitis was 3.9 for P. bivia (95% CI 1.5-5.7, p < 0.001) and 3.6
      for P. disiens (95%CI: 1.8-7.5, p < 0.001), and a diagnosis of BV for P. bivia
      (odds ratio: 5.3, 95%CI: 2.6 to 10.4, p < 0.001) and P. disiens (odds ratio: 4.4,
      95% CI: 2.2 to 8.8, p < 0.001). CONCLUSION: Higher vaginal bacterial counts can
      be found in women with BV and gingivitis in comparison to women with BV but not
      gingivitis. P. bivia and P. disiens may be of specific significance in a
      relationship between vaginal and gingival infections.

PMID- 19161596
TI  - Pseudo cardiac tamponade in the setting of excess pericardial fat.
AB  - Cardiac tamponade is the phenomenon of hemodynamic compromise caused by a
      pericardial effusion. Following a myocardial infarction, the most common causes
      of pericardial fluid include early pericarditis, Dressler's syndrome, and
      hemopericardium secondary to a free wall rupture. On transthoracic
      echocardiography, pericardial fluid appears as an echo-free space in between the
      visceral and parietal layers of the pericardium. Pericardial fat has a similar
      appearance on echocardiography and it may be difficult to discern the two
      entities. We present a case of a post-MI patient demonstrating pseudo tamponade
      physiology in the setting of excessive pericardial fat.

PMID- 19161598
TI  - The economic burden of inpatient paediatric care in Kenya: household and provider
      costs for treatment of pneumonia, malaria and meningitis.
AB  - BACKGROUND: Knowledge of treatment cost is essential in assessing cost
      effectiveness in healthcare. Evidence of the potential impact of implementing
      available interventions against childhood illnesses in developing countries
      challenges us to define the costs of treating these diseases. The purpose of this
      study is to describe the total costs associated with treatment of pneumonia,
      malaria and meningitis in children less than five years in seven Kenyan
      hospitals. METHODS: Patient resource use data were obtained from largely
      prospective evaluation of medical records and household expenditure during
      illness was collected from interviews with caretakers. The estimates for costs
      per bed day were based on published data. A sensitivity analysis was conducted
      using WHO-CHOICE values for costs per bed day. RESULTS: Treatment costs for 572
      children (pneumonia = 205, malaria = 211, meningitis = 102 and mixed diagnoses =
      54) and household expenditure for 390 households were analysed. From the provider
      perspective the mean cost per admission at the national hospital was US $95.58
      for malaria, US $177.14 for pneumonia and US $284.64 for meningitis. In the
      public regional or district hospitals the mean cost per child treated ranged from
      US $47.19 to US $81.84 for malaria and US $54.06 to US $99.26 for pneumonia. The
      corresponding treatment costs in the mission hospitals were between US $43.23 to
      US $88.18 for malaria and US $ 43.36 to US $142.22 for pneumonia. Meningitis was
      treated for US $ 189.41 at the regional hospital and US $ 201.59 at one mission
      hospital. The total treatment cost estimates were sensitive to changes in the
      source of bed day costs. The median treatment related household payments within
      quintiles defined by total household expenditure differed by type of facility
      visited. Public hospitals recovered up to 40% of provider costs through user
      charges while mission facilities recovered 44% to 100% of costs. CONCLUSION:
      Treatments cost for inpatient malaria, pneumonia and meningitis vary by facility
      type, with mission and tertiary referral facilities being more expensive compared
      to primary referral. Households of sick children contribute significantly towards
      provider cost through payment of user fees. These findings could be used in cost
      effectiveness analysis of health interventions.

PMID- 19161597
TI  - Notch signalling in the paraxial mesoderm is most sensitive to reduced Pofut1
      levels during early mouse development.
AB  - BACKGROUND: The evolutionarily conserved Notch signalling pathway regulates
      multiple developmental processes in a wide variety of organisms. One critical
      posttranslational modification of Notch for its function in vivo is the addition
      of O-linked fucose residues by protein O-fucosyltransferase 1 (POFUT1). In
      addition, POFUT1 acts as a chaperone and is required for Notch trafficking. Mouse
      embryos lacking POFUT1 function die with a phenotype indicative of global
      inactivation of Notch signalling. O-linked fucose residues on Notch can serve as
      substrates for further sugar modification by Fringe (FNG) proteins. Notch
      modification by Fringe differently affects the ability of ligands to activate
      Notch receptors in a context-dependent manner indicating a complex modulation of
      Notch activity by differential glycosylation. Whether the context-dependent
      effects of Notch receptor glycosylation by FNG reflect different requirements of
      distinct developmental processes for O-fucosylation by POFUT1 is unclear.
      RESULTS: We have identified and characterized a spontaneous mutation in the mouse
      Pofut1 gene, referred to as "compact axial skeleton" (cax). Cax carries an
      insertion of an intracisternal A particle retrotransposon into the fourth intron
      of the Pofut1 gene and represents a hypomorphic Pofut1 allele that reduces
      transcription and leads to reduced Notch signalling. Cax mutant embryos have
      somites of variable size, showed partly abnormal Lfng expression and,
      consistently defective anterior-posterior somite patterning and axial skeleton
      development but had virtually no defects in several other Notch-regulated early
      developmental processes outside the paraxial mesoderm that we analyzed.
      CONCLUSION: Notch-dependent processes apparently differ with respect to their
      requirement for levels of POFUT1. Normal Lfng expression and anterior-posterior
      somite patterning is highly sensitive to reduced POFUT1 levels in early mammalian
      embryos, whereas other early Notch-dependent processes such as establishment of
      left-right asymmetry or neurogenesis are not. Thus, it appears that in the
      presomitic mesoderm (PSM) Notch signalling is particularly sensitive to POFUT1
      levels. Reduced POFUT1 levels might affect Notch trafficking or overall O
      fucosylation. Alternatively, reduced O-fucosylation might preferentially affect
      sites that are substrates for LFNG and thus important for somite formation and
      patterning.

PMID- 19161599
TI  - A multivariate hierarchical Bayesian approach to measuring agreement in repeated
      measurement method comparison studies.
AB  - BACKGROUND: Assessing agreement in method comparison studies depends on two
      fundamentally important components; validity (the between method agreement) and
      reproducibility (the within method agreement). The Bland-Altman limits of
      agreement technique is one of the favoured approaches in medical literature for
      assessing between method validity. However, few researchers have adopted this
      approach for the assessment of both validity and reproducibility. This may be
      partly due to a lack of a flexible, easily implemented and readily available
      statistical machinery to analyse repeated measurement method comparison data.
      METHODS: Adopting the Bland-Altman framework, but using Bayesian methods, we
      present this statistical machinery. Two multivariate hierarchical Bayesian models
      are advocated, one which assumes that the underlying values for subjects remain
      static (exchangeable replicates) and one which assumes that the underlying values
      can change between repeated measurements (non-exchangeable replicates). RESULTS:
      We illustrate the salient advantages of these models using two separate datasets
      that have been previously analysed and presented; (i) assuming static underlying
      values analysed using both multivariate hierarchical Bayesian models, and (ii)
      assuming each subject's underlying value is continually changing quantity and
      analysed using the non-exchangeable replicate multivariate hierarchical Bayesian
      model. CONCLUSION: These easily implemented models allow for full parameter
      uncertainty, simultaneous method comparison, handle unbalanced or missing data,
      and provide estimates and credible regions for all the parameters of interest.
      Computer code for the analyses in also presented, provided in the freely
      available and currently cost free software package WinBUGS.

PMID- 19161600
TI  - The relationship between trust in mass media and the healthcare system and
      individual health: evidence from the AsiaBarometer Survey.
AB  - BACKGROUND: Vertical and horizontal trust, as dimensions of social capital, may
      be important determinants of health. As mass media campaigns have been used
      extensively to promote healthy lifestyles and convey health-related information,
      high levels of individual trust in the media may facilitate the success of such
      campaigns and, hence, have a positive influence on health. However, few studies
      have investigated the relationship between trust levels in mass media, an aspect
      of vertical trust, and health. METHODS: Based on cross-sectional data of the
      general population from the AsiaBarometer Survey (2003-2006), we analyzed the
      relationship between self-rated health and trust in mass media, using a
      multilevel logistic model, adjusted for age, gender, marital status, income,
      education, occupation, horizontal trust, and trust in the healthcare system.
      RESULTS: In a total of 39082 participants (mean age 38; 49% male), 26808 (69%)
      were classified as in good health. By the levels of trust in mass media, there
      were 6399 (16%) who reported that they trust a lot, 16327 (42%) reporting trust
      to a degree, 9838 (25%) who do not really trust, 3307 (9%) who do not trust at
      all, and 191 (0.5%) who have not thought about it. In the multilevel model, trust
      in mass media was associated with good health (do not trust at all as the base
      group): the odds ratios (OR) of 1.16 (95% confidence interval (CI) = 1.05-1.27)
      for do not really trust; OR of 1.35 (95% CI = 1.23-1.49) for trust to a degree,
      and 1.57 (95% CI = 1.36-1.81) for trust a lot. Horizontal trust and trust in the
      healthcare system were also associated with health. CONCLUSION: Vertical trust in
      mass media is associated with better health in Asian people. Since mass media is
      likely an important arena for public health, media trust should be enhanced to
      make people healthier.

PMID- 19161601
TI  - Differential effectiveness of Serratia plymuthica IC1270-induced systemic
      resistance against hemibiotrophic and necrotrophic leaf pathogens in rice.
AB  - BACKGROUND: Induced resistance is a state of enhanced defensive capacity
      developed by a plant reacting to specific biotic or chemical stimuli. Over the
      years, several forms of induced resistance have been characterized, including
      systemic acquired resistance, which is induced upon localized infection by an
      avirulent necrotizing pathogen, and induced systemic resistance (ISR), which is
      elicited by selected strains of nonpathogenic rhizobacteria. However, contrary to
      the relative wealth of information on inducible defense responses in
      dicotyledoneous plants, our understanding of the molecular mechanisms underlying
      induced resistance phenomena in cereal crops is still in its infancy. Using a
      combined cytomolecular and pharmacological approach, we analyzed the host defense
      mechanisms associated with the establishment of ISR in rice by the rhizobacterium
      Serratia plymuthica IC1270. RESULTS: In a standardized soil-based assay, root
      treatment with IC1270 rendered foliar tissues more resistant to the
      hemibiotrophic pathogen Magnaporthe oryzae, causal agent of the devastating rice
      blast disease. Analysis of the cytological and biochemical alterations associated
      with restriction of fungal growth in IC1270-induced plants revealed that IC1270
      primes rice for enhanced attacker-induced accumulation of reactive oxygen species
      (ROS) and autofluorescent phenolic compounds in and near epidermal cells
      displaying dense cytoplasmic granulation. Similar, yet more abundant, phenotypes
      of hypersensitively dying cells in the vicinity of fungal hyphae were evident in
      a gene-for-gene interaction with an avirulent M. oryzae strain, suggesting that
      IC1270-inducible ISR and R protein conditioned effector-triggered immunity (ETI)
      target similar defense mechanisms. Yet, this IC1270-inducible ISR response seems
      to act as a double-edged sword within the rice defense network as induced plants
      displayed an increased vulnerability to the necrotrophic pathogens Rhizoctonia
      solani and Cochliobolus miyabeanus. Artificial enhancement of ROS levels in
      inoculated leaves faithfully mimicked the opposite effects of IC1270 bacteria on
      aforementioned pathogens, suggesting a central role for oxidative events in the
      IC1270-induced resistance mechanism. CONCLUSION: Besides identifying ROS as
      modulators of antagonistic defense mechanisms in rice, this work reveals the
      mechanistic similarities between S. plymuthica-mediated ISR and R protein
      dictated ETI and underscores the importance of using appropriate innate defense
      mechanisms when breeding for broad-spectrum rice disease resistance.

PMID- 19161602
TI  - Psychological adjustment and quality of life in children and adolescents
      following open-heart surgery for congenital heart disease: a systematic review.
AB  - BACKGROUND: Children with congenital heart defects (CHD) requiring open-heart
      surgery are a group at high risk for health-related sequelae. Little consensus
      exists regarding their long-term psychological adjustment (PA) and health-related
      quality of life (QoL). Thus, we conducted a systematic review to determine the
      current knowledge on long-term outcome in this population. METHODS: We included
      randomized controlled trials, case control, or cohort studies published between
      1990-2008 evaluating self- and proxy-reported PA and QoL in patients aged between
      two and 17 years with a follow-up of at least two years after open heart surgery
      for CHD. RESULTS: Twenty-three studies assessing psychological parameters and 12
      studies assessing QoL were included. Methodological quality of the studies varied
      greatly with most studies showing a moderate quality. Results were as follows:
      (a) A considerable proportion of children experienced psychological maladjustment
      according to their parents; (b) studies on self-reported PA indicate a good
      outcome; (c) the studies on QoL suggest an impaired QoL for some children in
      particular for those with more severe cardiac disease; (d) parental reports of
      psychological maladjustment were related to severity of CHD and developmental
      delay. CONCLUSION: A significant proportion of survivors of open-heart surgery
      for CHD are at risk for psychological maladjustment and impaired QoL. Future
      research needs to focus on self-reports, QoL data and adolescents.

PMID- 19161603
TI  - Up-regulation and clinical relevance of novel helicase homologue DHX32 in
      colorectal cancer.
AB  - BACKGROUND: This study aimed to find novel biomarkers for colorectal cancer.
      METHODS: Fluorescent mRNA differential display PCR (DD-PCR) was used to screen
      the genes differentially expressed in colorectal cancer tissues and their
      adjacent tissues. The differentially expressed genes were confirmed by real-time
      PCR and then their clinical relevance (such as association with tumor location
      and lymph gland metastasis) was further investigated. RESULTS: We identified by
      DD-PCR a novel RNA helicase, DHX32, which showed higher expression in colorectal
      cancer tissues than their adjacent tissues, and this result was confirmed by real
      time RT-PCR. In addition, we found that the level of DHX32 gene expression in
      colorectal cancer was significantly associated with cancer location, lymph gland
      metastasis, cancer nodal status, differentiation grade, and Dukes, stage.
      CONCLUSION: DHX32 may play an important role in the development of colorectal
      cancer and could serve as a novel biomarker for colorectal cancer after
      additional investigation.

PMID- 19161604
TI  - Practice Nurses' views of their role in the management of Chronic Fatigue
      Syndrome/Myalagic Encephalitis: a qualitative study.
AB  - BACKGROUND: NICE guidelines suggest that patients with Chronic Fatigue
      Syndrome/Myalgic Encephalitis (CFS/ME) should be managed in Primary Care.
      Practice Nurses are increasingly being involved in the management of long-term
      conditions, so are likely to also have a growing role in managing CFS/ME. However
      their attitudes to, and experiences of patients with CFS/ME and its management
      must be explored to understand what barriers may exist in developing their role
      for this group of patients. The aim of this study was to explore Practice Nurses'
      understanding and beliefs about CFS/ME and its management. METHODS: Semi
      structured interviews with 29 Practice Nurses. Interviews were transcribed
      verbatim and an iterative approach used to develop themes from the dataset.
      RESULTS: Practice nurses had limited understanding about CFS/ME which had been
      largely gained through contact with patients, friends, personal experiences and
      the media rather than formal training. They had difficulty seeing CFS/ME as a
      long term condition. They did identify a potential role they could have in
      management of CFS/ME but devalued their own skills in psychological intervention,
      and suggested counselling would be an appropriate therapeutic option. They
      recognised a need for further training and on going supervision from both medical
      and psychological colleagues. Some viewed the condition as contentious and held
      pejorative views about CFS/ME. Such scepticism and negative attitudes will be a
      significant barrier to the management of patients with CFS/ME in primary care.
      CONCLUSION: The current role of Practice Nurses in the ongoing management of
      patients with CFS/ME is limited. Practice Nurses have little understanding of the
      evidence-base for treatment of CFS/ME, particularly psychological therapies,
      describing management options in terms of advice giving, self-help or
      counselling. Practice Nurses largely welcomed the potential development of their
      role in this area, but identified barriers and training needs which must be
      addressed to enable them to feel confident managing of patients with this
      condition. Training must begin by addressing negative attitudes to patients with
      CFS/ME.

PMID- 19161605
TI  - Referral from primary care to a physical activity programme: establishing long
      term adherence? A randomized controlled trial. Rationale and study design.
AB  - BACKGROUND: Declining physical activity is associated with a rising burden of
      global disease. There is little evidence about effective ways to increase
      adherence to physical activity. Therefore, interventions are needed that produce
      sustained increases in adherence to physical activity and are cost-effective. The
      purpose is to assess the effectiveness of a primary care physical activity
      intervention in increasing adherence to physical activity in the general
      population seen in primary care. METHOD AND DESIGN: Randomized controlled trial
      with systematic random sampling. A total of 424 subjects of both sexes will
      participate; all will be over the age of 18 with a low level of physical activity
      (according to the International Physical Activity Questionnaire, IPAQ), self
      employed and from 9 Primary Healthcare Centres (PHC). They will volunteer to
      participate in a physical activity programme during 3 months (24 sessions; 2
      sessions a week, 60 minutes per session).Participants from each PHC will be
      randomly allocated to an intervention (IG) and control group (CG). The following
      parameters will be assessed pre and post intervention in both groups: (1) health
      related quality of life (SF-12), (2) physical activity stage of change
      (Prochaska's stages of change), (3) level of physical activity (IPAQ-short
      version), (4) change in perception of health (vignettes from the Cooperative
      World Organization of National Colleges, Academies, and Academic Associations of
      Family Physicians, COOP/WONCA), (5) level of social support for the physical
      activity practice (Social Support for Physical Activity Scale, SSPAS), and (6)
      control based on analysis (HDL, LDL and glycated haemoglobin). Participants'
      frequency of visits to the PHC will be registered over the six months before and
      after the programme. There will be a follow up in a face to face interview three,
      six and twelve months after the programme, with the reduced version of IPAQ, SF
      12, SSPAS, and Prochaska's stages. DISCUSSION: The pilot study showed the
      effectiveness of an enhanced low-cost, evidence-based intervention in increased
      physical activity and improved social support. If successful in demonstrating
      long-term improvements, this randomised controlled trial will be the first
      sustainable physical activity intervention based in primary care in our country
      to demonstrate long-term adherence to physical activity. TRIAL REGISTRATION: A
      service of the U.S. National Institutes of Health. Developed by the National
      Library of Medicine. ClinicalTrials.gov ID: NCT00714831.

PMID- 19161607
TI  - Mistletoe treatment in cancer-related fatigue: a case report.
AB  - Cancer-related fatigue (CRF) is a major and very common disabling condition in
      cancer patients. Treatment options do exist but have limited therapeutic effects.
      Mistletoe extracts are widely-used complementary cancer treatments whose possible
      impact on CRF has not been investigated in detail. A 36-year-old Swedish woman
      with a 10-year history of recurrent breast cancer, suffering from severe CRF,
      started complementary cancer treatment with mistletoe extracts. Over two and a
      half years a correspondence was observed between the intensity of mistletoe
      therapy and the fatigue. Mistletoe extracts seemed to have a beneficial, dose
      dependent effect on CRF. Although such effect has also been noted in clinical
      studies, it has never been the subject of detailed investigation. More research
      should clarify these observations.

PMID- 19161606
TI  - Tracking the polio virus down the Congo River: a case study on the use of Google
      Earth in public health planning and mapping.
AB  - BACKGROUND: The use of GIS in public health is growing, a consequence of a
      rapidly evolving technology and increasing accessibility to a wider audience.
      Google Earth (GE) is becoming an important mapping infrastructure for public
      health. However, generating traditional public health maps for GE is still beyond
      the reach of most public health professionals. In this paper, we explain, through
      the example of polio eradication activities in the Democratic Republic of Congo,
      how we used GE Earth as a planning tool and we share the methods used to generate
      public health maps. RESULTS: The use of GE improved field operations and resulted
      in better dispatch of vaccination teams and allocation of resources. It also
      allowed the creation of maps of high quality for advocacy, training and to help
      understand the spatiotemporal relationship between all the entities involved in
      the polio outbreak and response. CONCLUSION: GE has the potential of making
      mapping available to a new set of public health users in developing countries.
      High quality and free satellite imagery, rich features including Keyhole Markup
      Language or image overlay provide a flexible but yet powerful platform that set
      it apart from traditional GIS tools and this power is still to be fully harnessed
      by public health professionals.

PMID- 19161608
TI  - Effectiveness of a web-based self-help smoking cessation intervention: protocol
      of a randomised controlled trial.
AB  - BACKGROUND: Cigarette smoking is a major risk factor for many chronic and fatal
      illnesses. Stopping smoking directly reduces those risks. The aim of this study
      is to investigate the effectiveness of a web-based interactive self-help
      programme for smoking cessation, known as the StopSite, by comparing it to an
      online self-help guide. Both interventions were based on cognitive-behavioural
      and self-control principles, but the former provided exercises, feedback and
      interactive features such as one-to-one chatrooms and a user forum, which
      facilitated mutual support and experience sharing. METHODS AND DESIGN: We
      conducted a randomised controlled trial to compare the interactive intervention
      with the self-help guide. The primary outcome measure was prolonged abstinence
      from smoking. Secondary outcomes were point-prevalence abstinence, number of
      cigarettes smoked, and incidence of quit attempts reported at follow-up
      assessments. Follow-up assessments took place three and six months after a one
      month grace period for starting the intervention after baseline. Analyses were
      based on intention-to-treat principles using a conservative imputation method for
      missing data, whereby non-responders were classified as smokers. DISCUSSION: The
      trial should add to the body of knowledge on the effectiveness of web-based self
      help smoking cessation interventions. Effective web-based programmes can
      potentially help large numbers of smokers to quit, thus having a major public
      health impact. TRIAL REGISTRATION: ISRCTN74423766.

PMID- 19161609
TI  - Identification of factor XI deficiency in Holstein cattle in Turkey.
AB  - BACKGROUND: Factor XI (FXI) is a plasma protein that participates in the
      formation of blood clots. Factor XI deficiency is autosomal recessive hereditary
      disorder that may be associated with excess bleeding in Holstein cattle. METHODS:
      In this study, 225 Holstein cows reared in Turkey were screened in order to
      identify FXI genotypes. DNA extractions were obtained from the fresh blood of the
      cows. Amplicons of FXI exon 12 were obtained by Polymerase Chain Reaction (PCR),
      and analyzed by 2% agarose gel electrophoresis stained with ethidium bromide.
      Additionally, all cows were confirmed by DNA sequencing to determine whether or
      not there was a mutant allele. RESULTS: Carriers of the FXI deficiency have two
      DNA fragments of 320 bp and 244 bp in size. The results of our study demonstrated
      that only four out of the 225 Holstein cows tested in Turkey carried the FXI
      deficiency. The frequency of the mutant FXI allele and the prevalence of
      heterozygous cows were found as 0.9% and 1.8%, respectively. CONCLUSION: The DNA
      based test determines all genotypes, regardless of phenotype or FXI activity. The
      mutation responsible for the FXI deficiency had not been detected in Holstein
      cattle in Turkey before prior to this study. The frequency of the mutant FXI
      allele needs to be confirmed by carrying out further analyses on cattle in Turkey
      and the selection programs should be developed to eliminate this genetic
      disorder.

PMID- 19161610
TI  - Chronic subacute bowel obstruction caused by carcinoid tumour misdiagnosed as
      irritable bowel syndrome: a case report.
AB  - BACKGROUND: Carcinoid tumours are well-differentiated neuroendocrine tumours with
      secretory properties. Although fairly rare, they are the most common malignancy
      seen to affect the distal small bowel. Presentation is often non-specific with
      symptoms mimicking those of irritable bowel syndrome. Given this, the condition
      is often diagnosed late following disease progression, by which time the
      prognosis is poor. CASE PRESENTATION: A 74 year old Caucasian lady presented with
      a two week history of loose stools, nausea and one episode of vomiting. This sub
      acute presentation occurred on a background of a four year history of
      intermittent abdominal pain and bloating, previously diagnosed as irritable bowel
      syndrome. CT scans identified dilated loops of small bowel proximal to a
      spiculated mass in the region of the terminal ileum. This ileal lesion was
      removed at laparotomy and identified as a carcinoid tumour. CONCLUSION: This case
      highlights the issue of misdiagnosis of intestinal malignancy as the benign
      condition of irritable bowel syndrome. There have been several other references
      to this happenstance in the literature, and the problem is reflected in the
      percentage of patients with widespread disease at the time of diagnosis.
      Prognosis in this condition can be dramatically improved with early diagnosis,
      and surgical management at this stage is often curative. For this reason it is
      imperative to keep this differential diagnosis in the back of one's mind when
      assessing patients presenting with symptoms of intermittent partial bowel
      obstruction. The clinical presentation of this tumour, along with investigation
      and management of these cases, is discussed here.

PMID- 19161611
TI  - The Nordic Maintenance Care Program: when do chiropractors recommend secondary
      and tertiary preventive care for low back pain?
AB  - BACKGROUND: Among chiropractors the use of long-term treatment is common, often
      referred to as "maintenance care". Although no generally accepted definition
      exists, the term has a self-explanatory meaning to chiropractic clinicians. In
      public health terms, maintenance care can be considered as both secondary and
      tertiary preventive care. The objective of this study was to explore what factors
      chiropractors consider before recommending maintenance care to patients with low
      back pain (LBP). METHOD: Structured focus group discussions with Swedish
      chiropractors were used to discuss pre-defined cases. A questionnaire was then
      designed on the basis of the information obtained. In the questionnaire,
      respondents were asked to grade the importance of several factors when
      considering recommending maintenance care to a patient. The grading was done on a
      straight line ranging from "Very important" to "Not at all important". All
      members of the Swedish Chiropractors' Association (SCA) were invited to
      participate in the discussions and in the questionnaire survey. RESULTS: Thirty
      six (22%) of SCA members participated in the group discussions and 129 (77%)
      returned the questionnaires. Ninety-eight percent of the questionnaire
      respondents claimed to believe that chiropractic care can prevent future relapses
      of back pain. According to the group discussions tertiary preventive care would
      be considered appropriate when a patient improves by 75% or more. According to
      the results of the questionnaire survey, two factors were considered as "very
      important" by more than 70% of the respondents in recommending secondary
      preventive care, namely frequency past year and frequency past 10 years of the
      low back pain problem. Eight other factors were considered "very important" by 50
      69% of the respondents, namely duration (over the past year and of the present
      attack), treatment (effect and durability), lifestyle, work conditions, and
      psychosocial factors (including attitude). CONCLUSION: The vast majority of our
      respondents believe that chiropractic treatment can prevent relapses of back
      pain. When recommending secondary preventive care, past frequency of the problem
      is considered. For tertiary preventive care, the patient needs to improve
      considerably before a recommendation of maintenance care is made.

PMID- 19161612
TI  - A case of Meigs syndrome mimicking metastatic breast carcinoma.
AB  - BACKGROUND: Adnexal masses are not uncommon in patients with breast cancer.
      Breast cancer and ovarian malignancies are known to be associated. In patients
      with breast cancer and co-existing pleural effusions, ascites and adnexal masses,
      the probability of disseminated disease is high. Nevertheless, benign ovarian
      masses can mimic this clinical picture when they are associated with Meigs'
      syndrome making the work-up and management of these patients challenging. To our
      knowledge, there are no similar reports in the literature and therefore we
      present this case to highlight this entity. CASE PRESENTATION: A 56-year old
      woman presented with a 4 cm, grade 2, invasive ductal carcinoma of her left
      breast. Pre-treatment staging investigations showed a 13.5 cm mass in her left
      ovary, a small amount of ascites and a large right pleural effusion. Serum tumour
      markers showed a raised CA125 supporting the malignant nature of the ovarian
      mass. The cytology from the pleural effusion was indeterminate but thoracoscopic
      biopsy failed to show malignancy. The patient was strongly against mastectomy and
      she was commenced on neo-adjuvant Letrozole 2.5 mg daily with a view to perform
      breast conserving surgery. After a good response to the hormone manipulation, the
      patient had breast conserving surgery, axillary sampling and laparoscopic
      excision of the ovarian mass which was eventually found to be a benign ovarian
      fibroma. CONCLUSION: Despite the high probability of disseminated malignancy when
      an ovarian mass associated with ascites if found in a patient with a breast
      cancer and pleural effusion, clinicians should be aware about rare benign
      syndromes, like Meigs', which may mimic a similar picture and mislead the
      diagnosis and management plan.

PMID- 19161613
TI  - Ecological association between a deprivation index and mortality in France over
      the period 1997 - 2001: variations with spatial scale, degree of urbanicity, age,
      gender and cause of death.
AB  - BACKGROUND: Spatial health inequalities have often been analysed in terms of
      deprivation. The aim of this study was to create an ecological deprivation index
      and evaluate its association with mortality over the entire mainland France
      territory. More specifically, the variations with the degree of urbanicity,
      spatial scale, age, gender and cause of death, which influence the association
      between mortality and deprivation, have been described. METHODS: The deprivation
      index, 'FDep99', was developed at the 'commune'(smallest administrative unit in
      France) level as the first component of a principal component analysis of four
      socioeconomic variables. Proxies of the Carstairs and Townsend indices were
      calculated for comparison. The spatial association between FDep99 and mortality
      was studied using five different spatial scales, and by degree of urbanicity
      (five urban unit categories), age, gender and cause of death, over the period
      1997-2001. 'Avoidable' causes of death were also considered for subjects aged
      less than 65 years. They were defined as causes related to risk behaviour and
      primary prevention (alcohol, smoking, accidents). RESULTS: The association
      between the FDep99 index and mortality was positive and quasi-log-linear, for all
      geographic scales. The standardized mortality ratio (SMR) was 24% higher for the
      communes of the most deprived quintile than for those of the least deprived
      quintile. The between-urban unit category and between-region heterogeneities of
      the log-linear associations were not statistically significant. The association
      was positive for all the categories studied and was significantly greater for
      subjects aged less than 65 years, for men, and for 'avoidable' mortality. The
      amplitude and regularity of the associations between mortality and the Townsend
      and Carstairs indices were lower. CONCLUSION: The deprivation index proposed
      reflects a major part of spatial socioeconomic heterogeneity, in a homogeneous
      manner over the whole country. The index may be routinely used by healthcare
      authorities to observe, analyse, and manage spatial health inequalities.

PMID- 19161614
TI  - Delayed transfer of care from NHS secondary care to primary care in England: its
      determinants, effect on hospital bed days, prevalence of acute medical conditions
      and deaths during delay, in older adults aged 65 years and over.
AB  - BACKGROUND: The delay in discharge or transfer of care back to the community
      following an acute admission to the hospital in older adults has long been a
      recognized challenge in the UK. We examined the determinants and outcomes of
      delayed transfer of care in older adults. METHODS: A prospective observational
      study was conducted in a district general hospital with a catchment population of
      250,000 in England, UK. Those >or= 65 years admitted to two care of the elderly
      wards during February 2007 were identified and prospectively followed-up till
      their discharge. Data was presented descriptively. RESULTS: 36.7% (58/158) of
      patients had a delay in transfer of care. They tended to be older, had poorer pre
      morbid mobility, and were more likely to be confused at the time of admission.
      Compared to the 2003 National Audit Report, a significantly higher percentage
      (29.3%vs.17%) awaited therapist assessments or (27.6%vs.9%) domiciliary care,
      with a lower percentage (< 1%vs.14%) awaiting further NHS care. Of 18 in-patient
      deaths, five occurred during the delay. Seven patients developed medical
      conditions during the delay making them unfit for discharge. The number of extra
      bed days attributable to delayed discharges in this study was 682 (mean = 4.8)
      days. CONCLUSION: Awaiting therapy and domiciliary care input were significant
      contributing factors in delayed transfer of care. Similar local assessments could
      provide valuable information in identifying areas for improvement. Based on
      available current evidence, efficacy driven changes to the organisation and
      provision of support, for example rapid response delayed discharge services at
      the time of "fit to discharge" may help to improve the situation.

PMID- 19161616
TI  - Large-scale inference of the point mutational spectrum in human segmental
      duplications.
AB  - BACKGROUND: Recent segmental duplications are relatively large (> or = 1 kb)
      genomic regions of high sequence identity (> or = 90%). They cover approximately
      4-5% of the human genome and play important roles in gene evolution and genomic
      disease. The DNA sequence differences between copies of a segmental duplication
      represent the result of various mutational events over time, since any two
      duplication copies originated from the same ancestral DNA sequence. Based on this
      fact, we have developed a computational scheme for inference of point mutational
      events in human segmental duplications, which we collectively term duplication
      inferred mutations (DIMs). We have characterized these nucleotide substitutions
      by comparing them with high-quality SNPs from dbSNP, both in terms of sequence
      context and frequency of substitution types. RESULTS: Overall, DIMs show a lower
      ratio of transitions relative to transversions than SNPs, although this ratio
      approaches that of SNPs when considering DIMs within most recent duplications.
      Our findings indicate that DIMs and SNPs in general are caused by similar
      mutational mechanisms, with some deviances at the CpG dinucleotide. Furthermore,
      we discover a large number of reference SNPs that coincide with computationally
      inferred DIMs. The latter reflects how sequence variation in duplicated sequences
      can be misinterpreted as ordinary allelic variation. CONCLUSION: In summary, we
      show how DNA sequence analysis of segmental duplications can provide a genome
      wide mutational spectrum that mirrors recent genome evolution. The inferred set
      of nucleotide substitutions represents a valuable complement to SNPs for the
      analysis of genetic variation and point mutagenesis.

PMID- 19161615
TI  - The balance of Polo-like kinase 1 in tumorigenesis.
AB  - Polo-like kinase 1 (Plk1) belongs to a family of conserved serine/threonine
      kinases with a polo-box domain, which have similar but non-overlapping functions
      in the cell cycle progression. Plk1 plays a key role to ensure the normal
      mitosis. Interestingly, overexpression of Plk1 is associated with tumor
      development and could serve as a prognostic marker for many cancers. Due to Plk1
      overexpression, several Plk1 inhibitors have been developed and tested for the
      cancer treatment. However, in a recent study, it has been suggested that down
      regulation of Plk1 could also induce aneuploidy and tumor formation in vivo.
      Therefore, a normal level of Plk1 is important for mitosis. And caution should be
      taken when Plk1 inhibitors are used in the clinical trial and their side effects
      including tumorigenesis should be carefully evaluated.

PMID- 19161618
TI  - The use of magical plants by curanderos in the Ecuador highlands.
AB  - Although the use of plants for treating supernaturally caused illnesses (e.g.,
      soul loss, evil wind, witchcraft) has been documented in the Ecuador highlands,
      so-called magical plants have received much less focused attention than plants
      used for treating naturalistic disorders. Drawing on interviews done in 2002 and
      2003 with 116 curanderos residing in the Ecuador highlands, this paper examines
      the characteristics of plants identified as magical, how they are used, and how
      the study of magical plants provides insights into the mindscape of residents of
      the highlands.

PMID- 19161617
TI  - Genetic and other factors determining mannose-binding lectin levels in American
      Indians: the Strong Heart Study.
AB  - BACKGROUND: Mannose-binding lectin (MBL) forms an integral part of the innate
      immune system. Persistent, subclinical infections and chronic inflammatory states
      are hypothesized to contribute to the pathogenesis of atherosclerosis. MBL gene
      (MBL2) variants with between 12 to 25% allele frequency in Caucasian and other
      populations, result in markedly reduced expression of functional protein.
      Prospective epidemiologic studies, including a nested, case-control study from
      the present population, have demonstrated the ability of MBL2 genotypes to
      predict complications of atherosclerosis,. The genetic control of MBL2 expression
      is complex and genetic background effects in specific populations are largely
      unknown. METHODS: The Strong Heart Study is a longitudinal, cohort study of
      cardiovascular disease among American Indians. A subset of individuals genotyped
      for the above mentioned case-control study were selected for analysis of
      circulating MBL levels by double sandwich ELISA method. Mean MBL levels were
      compared between genotypic groups and multivariate regression was used to
      determine other independent factors influencing MBL2 expression. RESULTS: Our
      results confirm the effects of variant structural (B, C, and D) and promoter (H
      and Y) alleles that have been seen in other populations. In addition, MBL levels
      were found to be positively associated with male gender and hemoglobin A1c
      levels, but inversely related to triglyceride levels. Correlation was not found
      between MBL and other markers of inflammation. CONCLUSION: New data is presented
      concerning the effects of known genetic variants on MBL levels in an American
      Indian population, as well as the relationship of MBL2 expression to clinical and
      environmental factors, including inflammatory markers.

PMID- 19161619
TI  - A genome-wide genetic signature of Jewish ancestry perfectly separates
      individuals with and without full Jewish ancestry in a large random sample of
      European Americans.
AB  - BACKGROUND: It was recently shown that the genetic distinction between self
      identified Ashkenazi Jewish and non-Jewish individuals is a prominent component
      of genome-wide patterns of genetic variation in European Americans. No study
      however has yet assessed how accurately self-identified (Ashkenazi) Jewish
      ancestry can be inferred from genomic information, nor whether the degree of
      Jewish ancestry can be inferred among individuals with fewer than four Jewish
      grandparents. RESULTS: Using a principal components analysis, we found that the
      individuals with full Jewish ancestry formed a clearly distinct cluster from
      those individuals with no Jewish ancestry. Using the position on the first
      principal component axis, every single individual with self-reported full Jewish
      ancestry had a higher score than any individual with no Jewish ancestry.
      CONCLUSIONS: Here we show that within Americans of European ancestry there is a
      perfect genetic corollary of Jewish ancestry which, in principle, would permit
      near perfect genetic inference of Ashkenazi Jewish ancestry. In fact, even
      subjects with a single Jewish grandparent can be statistically distinguished from
      those without Jewish ancestry. We also found that subjects with Jewish ancestry
      were slightly more heterozygous than the subjects with no Jewish ancestry,
      suggesting that the genetic distinction between Jews and non-Jews may be more
      attributable to a Near-Eastern origin for Jewish populations than to population
      bottlenecks.

PMID- 19161620
TI  - An open access database of genome-wide association results.
AB  - BACKGROUND: The number of genome-wide association studies (GWAS) is growing
      rapidly leading to the discovery and replication of many new disease loci.
      Combining results from multiple GWAS datasets may potentially strengthen previous
      conclusions and suggest new disease loci, pathways or pleiotropic genes. However,
      no database or centralized resource currently exists that contains anywhere near
      the full scope of GWAS results. METHODS: We collected available results from 118
      GWAS articles into a database of 56,411 significant SNP-phenotype associations
      and accompanying information, making this database freely available here. In
      doing so, we met and describe here a number of challenges to creating an open
      access database of GWAS results. Through preliminary analyses and
      characterization of available GWAS, we demonstrate the potential to gain new
      insights by querying a database across GWAS. RESULTS: Using a genomic bin-based
      density analysis to search for highly associated regions of the genome, positive
      control loci (e.g., MHC loci) were detected with high sensitivity. Likewise, an
      analysis of highly repeated SNPs across GWAS identified replicated loci (e.g.,
      APOE, LPL). At the same time we identified novel, highly suggestive loci for a
      variety of traits that did not meet genome-wide significant thresholds in prior
      analyses, in some cases with strong support from the primary medical genetics
      literature (SLC16A7, CSMD1, OAS1), suggesting these genes merit further study.
      Additional adjustment for linkage disequilibrium within most regions with a high
      density of GWAS associations did not materially alter our findings. Having a
      centralized database with standardized gene annotation also allowed us to examine
      the representation of functional gene categories (gene ontologies) containing one
      or more associations among top GWAS results. Genes relating to cell adhesion
      functions were highly over-represented among significant associations (p < 4.6 x
      10(-14)), a finding which was not perturbed by a sensitivity analysis.
      CONCLUSION: We provide access to a full gene-annotated GWAS database which could
      be used for further querying, analyses or integration with other genomic
      information. We make a number of general observations. Of reported associated
      SNPs, 40% lie within the boundaries of a RefSeq gene and 68% are within 60 kb of
      one, indicating a bias toward gene-centricity in the findings. We found
      considerable heterogeneity in information available from GWAS suggesting the
      wider community could benefit from standardization and centralization of results
      reporting.

PMID- 19161621
TI  - Pediatric trauma deaths are predominated by severe head injuries during spring
      and summer.
AB  - BACKGROUND: Trauma is the most prevalent cause of death in the young. Insight
      into cause and time of fatal pediatric and adolescent trauma is important for
      planning trauma care and preventive measures. Our aim was to analyze cause,
      severity, mode and seasonal aspects of fatal pediatric trauma. METHODS: Review of
      all consecutive autopsies for pediatric fatal trauma during a 10-year period
      within a defined population. RESULTS: Of all pediatric trauma deaths (n = 36),
      70% were males, with the gender increasing with age. Median age was 13 years
      (range 2-17). Blunt trauma predominated (by road traffic accidents) with most (n
      = 15; 42%) being "soft" victims, such as pedestrians/bicyclist and, 13 (36%)
      drivers or passengers in motor vehicles.Penetrating trauma caused only 3 deaths.
      Prehospital deaths (58%) predominated. 15 children (all intubated) reached
      hospital alive and had severely deranged vital parameters: 8 were hypotensive
      (SBP < 90 mmHg), 13 were in respiratory distress, and 14 had GCS < 8 on arrival.
      Emergency procedures were initiated (i.e. neurosurgical decompression, abdominal
      surgery or pelvic fixation for hemorrhage) in 12 patients. Probability of
      survival (Ps) was < 33% in over 75% of the fatalities. A bimodal death pattern
      was evident; the initial peak by CNS injuries and exsanguinations, the latter
      peak by CNS alone. Most fatalities occurred during spring (53%) or summertime
      (25%). CONCLUSION: Fatal pediatric trauma occurs most frequently in boys during
      spring/summer, associated with severe head injuries and low probability of
      survival. Preventive measures appear mandated in order to reduce this mortality
      in this age group.

PMID- 19161622
TI  - Molecular identification of CTX-M and blaOXY/K1 beta-lactamase genes in
      Enterobacteriaceae by sequencing of universal M13-sequence tagged PCR-amplicons.
AB  - BACKGROUND: Plasmid encoded blaCTX-M enzymes represent an important sub-group of
      class A beta-lactamases causing the ESBL phenotype which is increasingly found in
      Enterobacteriaceae including Klebsiella spp. Molecular typing of clinical ESBL
      isolates has become more and more important for prevention of the dissemination
      of ESBL-producers among nosocomial environment. METHODS: Multiple displacement
      amplified DNA derived from 20 K. pneumoniae and 34 K. oxytoca clinical isolates
      with an ESBL-phenotype was used in a universal CTX-M PCR amplification assay.
      Identification and differentiation of blaCTX-M and blaOXY/K1 sequences was
      obtained by DNA sequencing of M13-sequence-tagged CTX-M PCR-amplicons using a M13
      specific sequencing primer. RESULTS: Nine out of 20 K. pneumoniae clinical
      isolates had a blaCTX-M genotype. Interestingly, we found that the universal
      degenerated primers also amplified the chromosomally located K1-gene in all 34 K.
      oxytoca clinical isolates. Molecular identification and differentiation between
      blaCTX-M and blaOXY/K1-genes could only been achieved by sequencing of the PCR
      amplicons. In silico analysis revealed that the universal degenerated CTX-M
      primer-pair used here might also amplify the chromosomally located blaOXY and K1
      genes in Klebsiella spp. and K1-like genes in other Enterobacteriaceae.
      CONCLUSION: The PCR-based molecular typing method described here enables a rapid
      and reliable molecular identification of blaCTX-M, and blaOXY/K1-genes. The
      principles used in this study could also be applied to any situation in which
      antimicrobial resistance genes would need to be sequenced.

PMID- 19161624
TI  - Hidrocystoma of the external auditory canal: a case report.
AB  - BACKGROUND: Apocrine hydrocystomas arising in the external auditory canal are
      very rare. In this report a clinical case of apocrine hydrocystoma located in the
      cartilaginous part of the external auditory canal is presented. CASE
      PRESENTATION: A 64-year-old Caucasian female patient presented with a solitary
      nodule, located in the outer part of the external ear canal after repeated
      episodes of external otitis. For diagnostic purposes, computerized tomography was
      used. The patient underwent an excisional biopsy of the mass via an intra-aural
      incision and the surgical specimen was sent for histopathologic examination.
      CONCLUSION: An apocrine hidrocystoma inside the auricular canal is uncommon. It
      can cause recurrent external otitis and conductive hearing loss and should be
      treated with wide local excision and reconstruction of the external auditory
      canal for diagnostic and therapeutic purposes.

PMID- 19161623
TI  - HCV-related burden of disease in Europe: a systematic assessment of incidence,
      prevalence, morbidity, and mortality.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a leading cause of chronic liver disease,
      end-stage cirrhosis, and liver cancer, but little is known about the burden of
      disease caused by the virus. We summarised burden of disease data presently
      available for Europe, compared the data to current expert estimates, and
      identified areas in which better data are needed. METHODS: Literature and
      international health databases were systematically searched for HCV-specific
      burden of disease data, including incidence, prevalence, mortality, disability
      adjusted life-years (DALYs), and liver transplantation. Data were collected for
      the WHO European region with emphasis on 22 countries. If HCV-specific data were
      unavailable, these were calculated via HCV-attributable fractions. RESULTS: HCV
      specific burden of disease data for Europe are scarce. Incidence data provided by
      national surveillance are not fully comparable and need to be standardised. HCV
      prevalence data are often inconclusive. According to available data, an estimated
      7.3-8.8 million people (1.1-1.3%) are infected in our 22 focus countries. HCV
      specific mortality, DALY, and transplantation data are unavailable. Estimations
      via HCV-attributable fractions indicate that HCV caused more than 86000 deaths
      and 1.2 million DALYs in the WHO European region in 2002. Most of the DALYs (95%)
      were accumulated by patients in preventable disease stages. About one-quarter of
      the liver transplants performed in 25 European countries in 2004 were
      attributable to HCV. CONCLUSION: Our results indicate that hepatitis C is a major
      health problem and highlight the importance of timely antiviral treatment.
      However, data on the burden of disease of hepatitis C in Europe are scarce,
      outdated or inconclusive, which indicates that hepatitis C is still a neglected
      disease in many countries. What is needed are public awareness, co-ordinated
      action plans, and better data. European physicians should be aware that many
      infections are still undetected, provide timely testing and antiviral treatment,
      and avoid iatrogenic transmission.

PMID- 19161625
TI  - Umbilical artery tone in maternal obesity.
AB  - BACKGROUND: The increasing prevalence of obesity constitutes a major health
      problem in obstetrics with implications for feto-maternal growth and wellbeing.
      This study investigated and compared the contractile properties of umbilical
      arteries excised from obese women, with those excised from women with a normal
      body mass index (BMI). METHODS: Sections of umbilical artery were obtained from
      umbilical cord samples immediately after delivery and mounted for isometric
      recording in organ tissue baths under physiological conditions. Cumulative
      additions of 5-Hydroxytryptamine (5-HT) and Prostaglandin F-2alpha (PgF2alpha)
      were added in the concentration range of 1 nmol/L to 10 micromol/L. Control
      vessels were exposed to Krebs physiological salt solution (PSS) only. The
      resultant effects of each drug addition were measured using the Powerlab hardware
      unit. RESULTS: 5-HT exerted a significant effect on human umbilical artery tone
      at concentrations of 100 nmol/L, 1 micromol/L, and 10 micromol/L in normal (n =
      5; P < 0.05) and obese (n = 5; P < 0.05) women. The contractile effect was
      significantly greater in vessels from obese women {Mean Maximum Tension (MMT) =
      4.2532 g} than in those from women of normal BMI (MMT = 2.97 g; P < 0.05).
      PgF2alpha exerted a significant contractile effect on vessels at 1 micromol/L and
      10 micromol/L concentrations when compared with controls (n = 5; P < 0.05). There
      was a non-significant trend towards an enhanced tone response in vessels from
      obese women (MMT = 3.02 g; n = 5), in comparison to vessels from women of a
      normal BMI (MMT = 2.358 g; n = 5; P > 0.05). CONCLUSION: These findings support
      the hypothesis that endogenous regulation of umbilical artery tone is altered in
      association with maternal obesity. This may be linked to the cardiovascular
      effects of secretory products of adipose tissue, with implications for the feto
      maternal circulation.

PMID- 19161627
TI  - Capillary hemangioma of cauda equina: a case report.
AB  - BACKGROUND: Capillary hemangiomas of spinal nerve root, mostly affecting the
      cauda equina, are extremely rare. CASE PRESENTATION: A 20-year old man was
      presented with back pain, radiculopathy, and urogenital symptoms. Magnetic
      resonance images revealed an intradural extramedullary mass, isointense in T1
      weighted and hyperintense in T2-weighted images, with noticeable post injection
      enhancement. The clinical and radiological findings simulated neurinoma.However,
      a pinkish lesion was removed surgically and histopathological examination
      revealed lobules of capillary vessels separated by fibrous tissue, suggesting
      capillary hemangioma. CONCLUSION: Although rare and sometimes indistinguishable
      from more common lesion, capillary hemangioma should be in differential diagnosis
      of any enhancing intradural extramedullary mass at the level of cauda equina or
      conus medullaris.

PMID- 19161626
TI  - Medicago truncatula and Glomus intraradices gene expression in cortical cells
      harboring arbuscules in the arbuscular mycorrhizal symbiosis.
AB  - BACKGROUND: Most vascular flowering plants have the capacity to form symbiotic
      associations with arbuscular mycorrhizal (AM) fungi. The symbiosis develops in
      the roots where AM fungi colonize the root cortex and form arbuscules within the
      cortical cells. Arbuscules are enveloped in a novel plant membrane and their
      establishment requires the coordinated cellular activities of both symbiotic
      partners. The arbuscule-cortical cell interface is the primary functional
      interface of the symbiosis and is of central importance in nutrient exchange. To
      determine the molecular events the underlie arbuscule development and function,
      it is first necessary to identify genes that may play a role in this process.
      Toward this goal we used the Affymetrix GeneChip Medicago Genome Array to
      document the M. truncatula transcript profiles associated with AM symbiosis, and
      then developed laser microdissection (LM) of M. truncatula root cortical cells to
      enable analyses of gene expression in individual cell types by RT-PCR. RESULTS:
      This approach led to the identification of novel M. truncatula and G.
      intraradices genes expressed in colonized cortical cells and in arbuscules.
      Within the arbuscule, expression of genes associated with the urea cycle, amino
      acid biosynthesis and cellular autophagy was detected. Analysis of gene
      expression in the colonized cortical cell revealed up-regulation of a lysine
      motif (LysM)-receptor like kinase, members of the GRAS transcription factor
      family and a symbiosis-specific ammonium transporter that is a likely candidate
      for mediating ammonium transport in the AM symbiosis. CONCLUSION: Transcript
      profiling using the Affymetrix GeneChip Medicago Genome Array provided new
      insights into gene expression in M. truncatula roots during AM symbiosis and
      revealed the existence of several G. intraradices genes on the M. truncatula
      GeneChip. A laser microdissection protocol that incorporates low-melting
      temperature Steedman's wax, was developed to enable laser microdissection of M.
      truncatula root cortical cells. LM coupled with RT-PCR provided spatial gene
      expression information for both symbionts and expanded current information
      available for gene expression in cortical cells containing arbuscules.

PMID- 19161628
TI  - Expression of genes associated with carbohydrate metabolism in cotton stems and
      roots.
AB  - BACKGROUND: Cotton (Gossypium hirsutum L) is an important crop worldwide that
      provides fiber for the textile industry. Cotton is a perennial plant that stores
      starch in stems and roots to provide carbohydrates for growth in subsequent
      seasons. Domesticated cotton makes these reserves available to developing seeds
      which impacts seed yield. The goals of these analyses were to identify genes and
      physiological pathways that establish cotton stems and roots as physiological
      sinks and investigate the role these pathways play in cotton development during
      seed set. RESULTS: Analysis of field-grown cotton plants indicated that starch
      levels peaked about the time of first anthesis and then declined similar to
      reports in greenhouse-grown cotton plants. Starch accumulated along the length of
      the stem and the shape and size of the starch grains from stems were easily
      distinguished from transient starch. Microarray analyses compared gene expression
      in tissues containing low levels of starch with tissues rapidly accumulating
      starch. Statistical analysis of differentially expressed genes indicated
      increased expression among genes associated with starch synthesis, starch
      degradation, hexose metabolism, raffinose synthesis and trehalose synthesis. The
      anticipated changes in these sugars were largely confirmed by measuring soluble
      sugars in selected tissues. CONCLUSION: In domesticated cotton starch stored
      prior to flowering was available to support seed production. Starch accumulation
      observed in young field-grown plants was not observed in greenhouse grown plants.
      A suite of genes associated with starch biosynthesis was identified. The pathway
      for starch utilization after flowering was associated with an increase in
      expression of a glucan water dikinase gene as has been implicated in utilization
      of transient starch. Changes in raffinose levels and levels of expression of
      genes controlling trehalose and raffinose biosynthesis were also observed in
      vegetative cotton tissues as plants age.

PMID- 19161629
TI  - Human papillomavirus (HPV) in breast tumors: prevalence in a group of Mexican
      patients.
AB  - BACKGROUND: Breast cancer is one of the main health problems in developed
      countries, occupying first place in mortality in women. It is well-known that
      there are risk factors associated with breast cancer development. Nonetheless, in
      50-80% of cases known risk factors have not been identified, this has generated
      the attempt to identify new factors related with this neoplasia as viral
      infections. The aim of this work is investigate the prevalence of HPV DNA in
      patients with breast lesions at the Instituto Nacional de Cancerologia de Mexico.
      METHODS: Fifty-one cases of breast cancer were selected from the files of the
      institute and compared by age and tumor size with 43 cases of non malignant
      breast lesions (fibroadenoma, fibrocystic disease and phyllodes tumor). Paraffin
      embedded specimens were selected, HPV DNA was analyzed by polymerase chain
      reaction (PCR) and sequenced for different types of HPV in case of positivity for
      HPV-DNA. Descriptive analysis of clinical and pathological variables was
      performed and comparisons between positive and negative cases was done. RESULTS:
      All patients were mexican, mean age was 53.3, median age of menarche was 13 and
      median tumor size 9 cms. Cervicovaginal cytology was performed to all patients, 1
      patient (1.9%) of cancer group had HPV and none in the other group, no cases were
      diagnosed with cervical dysplasia. In the group of carcinomas 36 (70.5%) were
      negative and 15 (29.4%) were positive to HPV-DNA, 10(66.6%) were positive for HPV
      16, 3(20%) for HPV 18, two cases (13.4%) were positive for both. In the group of
      benign conditions all were negative to HPV-DNA. CONCLUSION: Presence of HPV in
      breast cancer in our group of cases is high in comparison to other authors;
      larger numbers of cases need to be analyzed in order to establish the exact role
      of this virus in the pathogenesis of breast cancer.

PMID- 19161630
TI  - Characterization of taxonomically restricted genes in a phylum-restricted cell
      type.
AB  - BACKGROUND: Despite decades of research, the molecular mechanisms responsible for
      the evolution of morphological diversity remain poorly understood. While current
      models assume that species-specific morphologies are governed by differential use
      of conserved genetic regulatory circuits, it is debated whether non-conserved
      taxonomically restricted genes are also involved in making taxonomically relevant
      structures. The genomic resources available in Hydra, a member of the early
      branching animal phylum Cnidaria, provide a unique opportunity to study the
      molecular evolution of morphological novelties such as the nematocyte, a cell
      type characteristic of, and unique to, Cnidaria. RESULTS: We have identified
      nematocyte-specific genes by suppression subtractive hybridization and find that
      a considerable portion has no homologues to any sequences in animals outside
      Hydra. By analyzing the transcripts of these taxonomically restricted genes and
      mining of the Hydra magnipapillata genome, we find unexpected complexity in gene
      structure and transcript processing. Transgenic Hydra expressing the green
      fluorescent protein reporter under control of one of the taxonomically restricted
      gene promoters recapitulate faithfully the described expression pattern,
      indicating that promoters of taxonomically restricted genes contain all elements
      essential for spatial and temporal control mechanisms. Surprisingly, phylogenetic
      footprinting of this promoter did not reveal any conserved cis-regulatory
      elements. CONCLUSIONS: Our findings suggest that taxonomically restricted genes
      are involved in the evolution of morphological novelties such as the cnidarian
      nematocyte. The transcriptional regulatory network controlling taxonomically
      restricted gene expression may contain not yet characterized transcription
      factors or cis-regulatory elements.

PMID- 19161631
TI  - Exercise therapy for prevention of falls in people with Parkinson's disease: a
      protocol for a randomised controlled trial and economic evaluation.
AB  - BACKGROUND: People with Parkinson's disease are twice as likely to be recurrent
      fallers compared to other older people. As these falls have devastating
      consequences, there is an urgent need to identify and test innovative
      interventions with the potential to reduce falls in people with Parkinson's
      disease. The main objective of this randomised controlled trial is to determine
      whether fall rates can be reduced in people with Parkinson's disease using
      exercise targeting three potentially remediable risk factors for falls (reduced
      balance, reduced leg muscle strength and freezing of gait). In addition we will
      establish the cost effectiveness of the exercise program from the health
      provider's perspective. METHODS/DESIGN: 230 community-dwelling participants with
      idiopathic Parkinson's disease will be recruited. Eligible participants will also
      have a history of falls or be identified as being at risk of falls on assessment.
      Participants will be randomly allocated to a usual-care control group or an
      intervention group which will undertake weight-bearing balance and strengthening
      exercises and use cueing strategies to address freezing of gait. The intervention
      group will choose between the home-based or support group-based mode of the
      program. Participants in both groups will receive standardized falls prevention
      advice. The primary outcome measure will be fall rates. Participants will record
      falls and medical interventions in a diary for the duration of the 6-month
      intervention period. Secondary measures include the Parkinson's Disease Falls
      Risk Score, maximal leg muscle strength, standing balance, the Short Physical
      Performance Battery, freezing of gait, health and well being, habitual physical
      activity and positive and negative affect schedule. DISCUSSION: No adequately
      powered studies have investigated exercise interventions aimed at reducing falls
      in people with Parkinson's disease. This trial will determine the effectiveness
      of the exercise intervention in reducing falls and its cost effectiveness. This
      pragmatic program, if found to be effective, has the potential to be implemented
      within existing community services. TRIAL REGISTRATION: The protocol for this
      study is registered with the Australian New Zealand Clinical Trials Registry
      (ACTRN12608000303347).

PMID- 19161632
TI  - Four novel mutations in the lactase gene (LCT) underlying congenital lactase
      deficiency (CLD).
AB  - BACKGROUND: Congenital lactase deficiency (CLD) is a severe gastrointestinal
      disorder of newborns. The diagnosis is challenging and based on clinical symptoms
      and low lactase activity in intestinal biopsy specimens. The disease is enriched
      in Finland but is also present in other parts of the world. Mutations encoding
      the lactase (LCT) gene have recently been shown to underlie CLD. The purpose of
      this study was to identify new mutations underlying CLD in patients with
      different ethnic origins, and to increase awareness of this disease so that the
      patients could be sought out and treated correctly. METHODS: Disaccharidase
      activities in intestinal biopsy specimens were assayed and the coding region of
      LCT was sequenced from five patients from Europe with clinical features
      compatible with CLD. In the analysis and prediction of mutations the following
      programs: ClustalW, Blosum62, PolyPhen, SIFT and Panther PSEC were used. RESULTS:
      Four novel mutations in the LCT gene were identified. A single nucleotide
      substitution leading to an amino acid change S688P in exon 7 and E1612X in exon
      12 were present in a patient of Italian origin. Five base deletion V565fsX567
      leading to a stop codon in exon 6 was found in one and a substitution R1587H in
      exon 12 from another Finnish patient. Both Finnish patients were heterozygous for
      the Finnish founder mutation Y1390X. The previously reported mutation G1363S was
      found in a homozygous state in two siblings of Turkish origin. CONCLUSION: This
      is the first report of CLD mutations in patients living outside Finland. It seems
      that disease is more common than previously thought. All mutations in the LCT
      gene lead to a similar phenotype despite the location and/or type of mutation.

PMID- 19161633
TI  - Prospects of psychosomatic medicine.

PMID- 19161634
TI  - Antiviral resistance during pandemic influenza: implications for stockpiling and
      drug use.
AB  - BACKGROUND: The anticipated extent of antiviral use during an influenza pandemic
      can have adverse consequences for the development of drug resistance and
      rationing of limited stockpiles. The strategic use of drugs is therefore a major
      public health concern in planning for effective pandemic responses. METHODS: We
      employed a mathematical model that includes both sensitive and resistant strains
      of a virus with pandemic potential, and applies antiviral drugs for treatment of
      clinical infections. Using estimated parameters in the published literature, the
      model was simulated for various sizes of stockpiles to evaluate the outcome of
      different antiviral strategies. RESULTS: We demonstrated that the emergence of
      highly transmissible resistant strains has no significant impact on the use of
      available stockpiles if treatment is maintained at low levels or the reproduction
      number of the sensitive strain is sufficiently high. However, moderate to high
      treatment levels can result in a more rapid depletion of stockpiles, leading to
      run-out, by promoting wide-spread drug resistance. We applied an antiviral
      strategy that delays the onset of aggressive treatment for a certain amount of
      time after the onset of the outbreak. Our results show that if high treatment
      levels are enforced too early during the outbreak, a second wave of infections
      can potentially occur with a substantially larger magnitude. However, a timely
      implementation of wide-scale treatment can prevent resistance spread in the
      population, and minimize the final size of the pandemic. CONCLUSION: Our results
      reveal that conservative treatment levels during the early stages of the
      outbreak, followed by a timely increase in the scale of drug-use, will offer an
      effective strategy to manage drug resistance in the population and avoid run-out.
      For a 1918-like strain, the findings suggest that pandemic plans should consider
      stockpiling antiviral drugs to cover at least 20% of the population.

PMID- 19161636
TI  - Care for chronic illness in Australian general practice - focus groups of chronic
      disease self-help groups over 10 years: implications for chronic care systems
      reforms.
AB  - BACKGROUND: Chronic disease is a major global challenge. However, chronic illness
      and its care, when intruding into everyday life, has received less attention in
      Asia Pacific countries, including Australia, who are in the process of
      transitioning to chronic disease orientated health systems. AIM: The study aims
      to examine experiences of chronic illness before and after the introduction of
      Australian Medicare incentives for longer consultations and structured health
      assessments in general practice. METHODS: Self-help groups around the conditions
      of diabetes, epilepsy, asthma and cancer identified key informants to participate
      in 4 disease specific focus groups. Audio taped transcripts of the focus groups
      were coded using grounded theory methodology. Key themes and lesser themes
      identified using a process of saturation until the study questions on needs and
      experiences of care were addressed. Thematic comparisons were made across the
      2002/3 and 1992/3 focus groups. FINDINGS: At times of chronic illness, there was
      need to find and then ensure access to 'the right GP'. The 'right GP or
      specialist' committed to an in-depth relationship of trust, personal rapport and
      understanding together with clinical and therapeutic competence. The 'right GP',
      the main specialist, the community nurse and the pharmacist were key providers,
      whose success depended on interprofessional communication. The need to trust and
      rely on care providers was balanced by the need for self-efficacy 'to be in
      control of disease and treatment' and 'to be your own case manager'. Changes in
      Medicare appeared to have little penetration into everyday perceptions of chronic
      illness burden or time and quality of GP care. Inequity of health system support
      for different disease groupings emerged. Diabetes, asthma and certain cancers,
      like breast cancer, had greater support, despite common experiences of disease
      burden, and a need for research and support programs. CONCLUSION: Core themes
      around chronic illness experience and care needs remained consistent over the 10
      year period. Reforms did not appear to alleviate the burden of chronic illness
      across disease groups, yet some were more privileged than others. Thus in the
      future, chronic care reforms should build from greater understanding of the needs
      of people with chronic illness.

PMID- 19161635
TI  - Comparison of mannitol and methacholine to predict exercise-induced
      bronchoconstriction and a clinical diagnosis of asthma.
AB  - BACKGROUND: Asthma can be difficult to diagnose, but bronchial provocation with
      methacholine, exercise or mannitol is helpful when used to identify bronchial
      hyperresponsiveness (BHR), a key feature of the disease. The utility of these
      tests in subjects with signs and symptoms of asthma but without a clear diagnosis
      has not been investigated. We investigated the sensitivity and specificity of
      mannitol to identify exercise-induced bronchoconstriction (EIB) as a
      manifestation of BHR; compared this with methacholine; and compared the
      sensitivity and specificity of mannitol and methacholine for a clinician
      diagnosis of asthma. METHODS: 509 people (6-50 yr) were enrolled, 78% were
      atopic, median FEV1 92.5% predicted, and a low NAEPPII asthma score of 1.2.
      Subjects with symptoms of seasonal allergy were excluded. BHR to exercise was
      defined as a > or = 10% fall in FEV1 on at least one of two tests, to
      methacholine a PC20 < or = 16 mg/ml and to mannitol a 15% fall in FEV1 at < or =
      635 mg or a 10% fall between doses. The clinician diagnosis of asthma was made on
      examination, history, skin tests, questionnaire and response to exercise but they
      were blind to the mannitol and methacholine results. RESULTS: Mannitol and
      methacholine were therapeutically equivalent to identify EIB, a clinician
      diagnosis of asthma, and prevalence of BHR. The sensitivity/specificity of
      mannitol to identify EIB was 59%/65% and for methacholine it was 56%/69%. The BHR
      was mild. Mean EIB % fall in FEV1 in subjects positive to exercise was 19%, (SD
      9.2), mannitol PD15 158 (CI:129,193) mg, and methacholine PC20 2.1(CI:1.7, 2.6)
      mg/ml. The prevalence of BHR was the same: for exercise (43.5%), mannitol
      (44.8%), and methacholine (41.6%) with a test agreement between 62 & 69%. The
      sensitivity and specificity for a clinician diagnosis of asthma was 56%/73% for
      mannitol and 51%/75% for methacholine. The sensitivity increased to 73% and 72%
      for mannitol and methacholine when two exercise tests were positive. CONCLUSION:
      In this group with normal FEV1, mild symptoms, and mild BHR, the sensitivity and
      specificity for both mannitol and methacholine to identify EIB and a clinician
      diagnosis of asthma were equivalent, but lower than previously documented in well
      defined populations. TRIAL REGISTRATION: This was a multi-center trial comprising
      25 sites across the United States of America.

PMID- 19161637
TI  - A rare case of multicentric synchronous bi-frontal glioma in a young female.
      Diagnostic and therapeutic problems: a case report.
AB  - Multicentric glioblastoma is a uncommon brain malignant tumour.We report the
      case of a 43-years-old woman, born in Ukraine and living in Italy, who manifested
      an initial isolated epileptic seizure and subsequent atypical psychiatric
      symptoms. Clinical neurological examination, Brain Computed Tomography and
      standard EEG examinations were negative at the moment of admission. A month
      later, she presented apathy, apraxia, psychomotor slowdown and expressive
      aphasia. A Magnetic Resonance Imaging examination showed a bi-frontal lesion. The
      patient underwent to two neurosurgical removals of the lesions: histological
      examination demonstrated the presence of a grade IV glioblastoma.Clinical onset,
      diagnostic and therapeutic problems are discussed.In case of atypical psychiatric
      presentation, it should be taken into consideration neoplastic, inflammatory or
      infective causes. Despite the absence of focal neurological signs and basal CT
      scan and EEG alterations, complementary imaging examinations, such as MRI and
      contrast enhancement CT, are necessary, especially when the conditions become
      quickly worse.

PMID- 19161638
TI  - The critical role of ERK in death resistance and invasiveness of hypoxia-selected
      glioblastoma cells.
AB  - BACKGROUND: The rapid growth of tumor parenchyma leads to chronic hypoxia that
      can result in the selection of cancer cells with a more aggressive behavior and
      death-resistant potential to survive and proliferate. Thus, identifying the key
      molecules and molecular mechanisms responsible for the phenotypic changes
      associated with chronic hypoxia has valuable implications for the development of
      a therapeutic modality. The aim of this study was to identify the molecular basis
      of the phenotypic changes triggered by chronic repeated hypoxia. METHODS: Hypoxia
      resistant T98G (HRT98G) cells were selected by repeated exposure to hypoxia and
      reoxygenation. Cell death rate was determined by the trypan blue exclusion method
      and protein expression levels were examined by western blot analysis. The
      invasive phenotype of the tumor cells was determined by the Matrigel invasion
      assay. Immunohistochemistry was performed to analyze the expression of proteins
      in the brain tumor samples. The Student T-test and Pearson Chi-Square test was
      used for statistical analyses. RESULTS: We demonstrate that chronic repeated
      hypoxic exposures cause T98G cells to survive low oxygen tension. As compared
      with parent cells, hypoxia-selected T98G cells not only express higher levels of
      anti-apoptotic proteins such as Bcl-2, Bcl-X(L), and phosphorylated ERK, but they
      also have a more invasive potential in Matrigel invasion chambers. Activation or
      suppression of ERK pathways with a specific activator or inhibitor, respectively,
      indicates that ERK is a key molecule responsible for death resistance under
      hypoxic conditions and a more invasive phenotype. Finally, we show that the
      activation of ERK is more prominent in malignant glioblastomas exposed to hypoxia
      than in low grade astrocytic glial tumors. CONCLUSION: Our study suggests that
      activation of ERK plays a pivotal role in death resistance under chronic hypoxia
      and phenotypic changes related to the invasive phenotype of HRT98G cells compared
      to parent cells.

PMID- 19161639
TI  - Decreasing dietary particle size of lupins increases apparent ileal amino acid
      digestibility and alters fermentation characteristics in the gastrointestinal
      tract of pigs.
AB  - Two experiments were conducted to examine the effects of lupin particle size on
      amino acid (AA) and energy digestibility and fermentation characteristics in
      pigs. Expt 1 examined the effects of lupin variety (cv. Tanjil and Mandelup) and
      lupin particle size (746, 888, 1099 and 1136 mum) on the total-tract apparent
      digestibility of dietary components in 63.5 (sd 7.28) kg pigs. While variety had
      no effect on total-tract apparent digestibility, decreasing particle size of
      lupins linearly increased total-tract apparent digestibility of crude protein of
      diets containing 350 g lupins per kg (P < 0.01). Expt 2 examined the effect of
      lupin particle size (567, 995, 1198, 1250 and 1304 mum) on digestion and
      fermentation characteristics in 29.8 (sd 2.9) kg pigs. Pigs were fed the
      respective diets ad libitum for the first 2 weeks and fed at three times
      maintenance energy level in the third week. Pigs were euthanised under sedation
      at 46.7 (sd 4.21) kg to collect digesta samples along the intestinal tract.
      Decreasing particle size increased apparent ileal and total-tract digestible N (P
      < 0.01) and the apparent and standardised ileal digestible AA content (P < 0.05-
      < 0.001) of lupins. Decreasing particle size of lupins linearly decreased the
      molar proportion of straight-chain volatile fatty acids (sum of acetic, propionic
      and butyric acids; VFAAPB), while branched-chain fatty acids (sum of valeric,
      caproic, isobutyric and isovaleric acids) were linearly increased (P < 0.001).
      The results demonstrated that particle size of lupins is a critical factor
      influencing nutrient, especially AA, utilisation efficiency and fermentation
      characteristics in the gastrointestinal tract of pigs.

PMID- 19161641
TI  - Assessing cost effectiveness of empirical and prophylactic therapy for managing
      leptospirosis outbreaks.
AB  - This study evaluates the utility and cost effectiveness of empirical and
      prophylactic antibiotic treatment of leptospirosis compared with conventional
      management. We developed decision trees comparing empirical antibiotic treatment
      (within 4-7 days of symptom onset) or prophylaxis to conventional antibiotic
      treatment (initiated 7 days post-onset). Costs were calculated using both US and
      Barbados pricing. Empirical treatment provided slightly lower probability of
      survival, while prophylactic treatment resulted in slightly higher survival
      rates. Antibiotic treatment initiated after 4-7 symptomatic days was ineffective
      in preventing serious health outcomes, but cost less with the exception of
      azithromycin (US pricing). Empirical treatment in Barbados cost less than
      conventional treatment. Prophylaxis reduced rare serious health outcomes and
      resulted in significant cost savings for the United States and Barbados.
      Prophylactic therapy for high-risk individuals or prompt diagnosis and early
      treatment (before 4 days of symptoms) appear to be cost-effective approaches to
      prevent severe complications of leptospirosis.

PMID- 19161640
TI  - Lipid peroxidation is not a prerequisite for the development of obesity and
      diabetes in high-fat-fed mice.
AB  - The mechanism, by which a high-fat (HF) diet could impair glucose metabolism, is
      not completely understood but could be related to inflammation, lipotoxicity and
      oxidative stress. Lipid peroxides have been proposed as key mediators of
      intracellular metabolic response. The purpose of the present study was to
      analyse, in mice fed with a HF diet, the possible association between obesity and
      glucose tolerance on the one hand, and between oxidative stress and lipid
      peroxidation on the other hand. The present results show that a HF diet (70 %
      energy as fat), v. a high-carbohydrate chow diet (control), increases body weight
      and fat mass development, and impairs glycaemia and insulinaemia within 4 weeks.
      It also promotes the expression of NADPH oxidase in the liver--signing both
      oxidative and inflammatory stress--but decreases thiobarbituric acid-reactive
      substances content in the liver as well as in epididymal, subcutaneous and
      visceral adipose tissues. HF diet, with elevated vitamin E content, induces high
      concentration of alpha-tocopherol in liver and adipose tissues, which contributes
      to the protection against lipid peroxidation. Thus, lipid peroxidation in key
      organs is not necessarily related to the development of metabolic disorders
      associated with diabetes and obesity.

PMID- 19161642
TI  - Genetic characteristics of pneumococcal disease in elderly patients before
      introducing the pneumococcal conjugate vaccine.
AB  - Streptococcus pneumoniae strains causing invasive pneumococcal disease (IPD) in
      the elderly population of England and Wales during the winter of 2003/2004 (1
      November 2003 to 30 April 2004) were characterized by serotyping and genotyping
      in order to determine their population structure in the elderly. Serotyping and
      multilocus sequence typing (MLST) were carried out on 542 invasive isolates
      referred to the Respiratory and Systemic Infection Laboratory. Pneumococci were
      distributed among 32 serotypes and 144 MLST sequence types. A high genetic
      diversity was observed within the major serotypes. Genetic relatedness varied
      with regard to serotype. Isolates within serotypes 3, 7F and 8 were the most
      genetically related whereas serotypes 6A and 19F comprised isolates originating
      from unrelated ancestors. There was indirect evidence that some pneumococci were
      derived from clones that had undergone capsular switching in the past.
      Interestingly one case of IPD was caused by a pneumococcus originating from a
      clone that had undergone capsular switching from serotype 18C, a serotype
      included in 7-valent pneumococcal conjugate vaccine (PCV) to serotype 1 (serotype
      not included in PCV) suggesting that virulent clones with the potential ability
      to evade PCV existed in the pneumococcal population prior to the routine
      introduction of this vaccine. Isolates from 28 cases of apparent 23-valent
      pneumococcal polysaccharide vaccine (PPV) failure were included but there was no
      evidence of the emergence of particular clones associated with vaccine failures.
      Longitudinal studies based on serotypic and genetic characterization of
      pneumococci are fundamental to understanding the impact of both PPV and PCV on
      the genetic structure of pneumococcal populations.

PMID- 19161643
TI  - Genetic relationship in southern African Crimean-Congo haemorrhagic fever virus
      isolates: evidence for occurrence of reassortment.
AB  - Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne viral zoonosis widely
      distributed in Africa, Asia and eastern Europe. Reassortment of CCHF genome
      segments has been shown to occur in nature. We therefore investigated the genetic
      relationship of southern African isolates using partial sequence data for each
      RNA segment, S, M and L, and comparing the tree topologies constructed using a
      neighbour joining method. A total of 21 southern African isolates were studied.
      The incongruencies which were identified in S, M and L sequence datasets involved
      group switching implying reassortment for 15 isolates. A higher fatality rate
      occurred in patients infected with isolates which had apparently acquired M
      segments from a group in which predominantly Asian strains are usually found.
      This suggests that reassortment may affect the pathogenicity of the virus.

PMID- 19161644
TI  - Investigation of a Q fever outbreak in a rural area of The Netherlands.
AB  - A Q fever outbreak occurred in the southeast of The Netherlands in spring and
      summer 2007. Risk factors for the acquisition of a recent Coxiella burnetii
      infection were studied. In total, 696 inhabitants in the cluster area were
      invited to complete a questionnaire and provide a blood sample for serological
      testing of IgG and IgM phases I and II antibodies against C. burnetii, in order
      to recruit seronegative controls for a case-control study. Questionnaires were
      also sent to 35 previously identified clinical cases. Limited environmental
      sampling focused on two goat farms in the area. Living in the east of the cluster
      area, in which a positive goat farm, cattle and small ruminants were situated,
      smoking and contact with agricultural products were associated with a recent
      infection. Information leaflets were distributed on a large scale to ruminant
      farms, including hygiene measures to reduce the risk of spread between animals
      and to humans.

PMID- 19161645
TI  - Study of the knowledge, attitudes and practices of physicians towards obesity
      management in primary health care in Bahrain.
AB  - AIM: To examine the opinions of physicians in Bahrain regarding their role in
      obesity control, and to evaluate their knowledge, attitudes and practices towards
      obesity prevention and management in primary health care. DESIGN: A cross
      sectional survey of physicians in Bahrain. A single-stage cluster sample was
      used, which included twelve health centres and 107 physicians. Ninety-seven
      physicians participated in the study with a 90% response rate. A self
      administered questionnaire was used to measure physicians' knowledge and
      practices, their perceived role and potential limitations. Correction for design
      effect and finite population were considered in the analysis. RESULTS: The
      majority of physicians in Bahrain (92%) were aware of the obesity epidemic and
      60% of them felt capable of assuming a major role in obesity control, regardless
      of their negative views towards the success rates of weight management. Only 36%
      agreed that they had effective weight-management practices. They were
      knowledgeable about weight-loss goals and showed a reasonable level of obesity
      identification, especially as part of chronic disease care (71%). Physicians
      reported a high rate of utilization of various weight-loss strategies, except for
      pharmacotherapy and surgery. The major barriers identified in patient care
      included time constraints (91%), lack of specialty clinics (81%), absence of
      guidelines (78%) and an inadequate number of dietitians (71%). Sixty-four per
      cent reported that training in lifestyle counselling and behaviour modification
      are important requirements. CONCLUSIONS: Physicians in Bahrain showed a
      reasonable level of interest in participating in obesity prevention and
      management. It seems that there would be a good opportunity for better practice
      if physicians were supported with appropriate training and the constraints of
      their working environment were adequately addressed.

PMID- 19161646
TI  - Gender heterogeneity in the association between lifestyles and non-fatal acute
      myocardial infarction.
AB  - OBJECTIVE: To evaluate the modification effect of sex in the association between
      lifestyles and acute myocardial infarction (AMI). DESIGN: Population-based case
      control study. Trained interviewers collected information using a standard
      structured questionnaire. Associations were estimated using unconditional
      logistic regression. The effect modification by sex was evaluated in the
      regression models, testing interaction terms between lifestyles and sex. SETTING:
      Porto, Portugal. SUBJECTS: Portuguese Caucasian adults, aged > or =18 years.
      Cases were patients consecutively admitted with an incident AMI during 1999-2003
      (n 918) and controls were a representative sample of non-institutionalized
      inhabitants of Porto with no evidence of previous clinical or silent infarction
      (n 2316). RESULTS: Cigarette smoking was positively associated with AMI in both
      men and women (smokers >15 cigarettes/d v. never smokers: OR = 9.11, 95% CI 4.83,
      17.20 for women; OR = 3.92, 95% CI 2.75, 5.58 for men; interaction term P value =
      0.001). A significant protective effect of moderate alcohol intake on AMI
      occurrence was found in women (0.1-15.0 g/d v. non-drinkers: OR = 0.48, 95% CI
      0.31, 0.74), but not in men. Fruit and vegetable intake, vitamin and mineral
      supplement use and leisure-time physical activity practice were found to decrease
      AMI risk, with similar effects between sexes. CONCLUSIONS: A strong positive
      association between smoking and AMI was found in women. Also, a protective effect
      of moderate alcohol intake was only found among females. Fruit and vegetable
      intake, vitamin and mineral supplement use and leisure-time physical activity
      practice were found to decrease AMI risk in both sexes.

PMID- 19161647
TI  - Effect of dietary factors on anaemia among rural elderly women in south-west
      China: a case-control study.
AB  - OBJECTIVE: To investigate the possible dietary risk factors for anaemia in rural
      elderly women. DESIGN: Case-control study conducted in 2005. Cases and matched
      controls were interviewed in person to elicit information on lifestyle, diet and
      individual health. Main foods and nutrients were calculated by three 24 h
      recalls; intake data of tea, edible oils and spices were from an FFQ. SETTING:
      Fourteen villages in two counties of Guangxi Province, south-west China.
      SUBJECTS: Four hundred and twenty anaemic cases and 433 matched controls, aged 50
      75 years. RESULTS: The mean consumption of animal foods for cases (82.4 g/d) was
      significantly lower than for controls (91.0 g/d), similarly for egg consumption
      (3.8 g/d for cases and 5.8 g/d for controls; P < 0.05). The absolute value of the
      Dietary Balance Index, low bound score (DBI_LBS) was significantly higher for
      cases than for controls (P < 0.05). Intakes of energy, protein, carbohydrate,
      vitamin A (retinol equivalents, RE), vitamin B1, riboflavin and Ca were
      significantly lower in cases than in controls (P < 0.05). There was no
      significant difference in Fe intake between the two groups. High intake of
      vitamin A (RE) was inversely associated with anaemia (quartile 4 v. quartile 1:
      OR = 0.6, P for linear trend = 0.02). The absolute value of DBI_LBS was
      positively related to anaemia (quartile 4 v. quartile 1: OR = 0.4, P for linear
      trend < 0.0001). CONCLUSION: For rural elderly women in south-west China, anaemia
      had a strong positive association with undernutrition and a negative association
      with vitamin A intake. Dietary Fe intake was not found to be an independent risk
      factor for anaemia.

PMID- 19161648
TI  - Adolescent dietary patterns are associated with lifestyle and family psycho
      social factors.
AB  - OBJECTIVE: Dietary intake during adolescence contributes to lifelong eating
      habits and the development of early risk factors for disease in adulthood. Few
      studies have examined the dietary patterns of adolescents and the social and
      environmental factors that may affect them during this life stage. The present
      study describes dietary patterns in a cohort of adolescents and examines their
      associations with socio-economic factors, as well as parental and adolescent risk
      factor behaviours. DESIGN: A semi-quantitative FFQ was used to assess study
      adolescents' usual dietary intake over the previous year. Information was
      collected on family functioning and various socio-economic and risk factor
      variables via questionnaire. Adolescents visited the study clinic for
      anthropometric measurements. SETTING: The Western Australian Pregnancy Cohort
      Study (Raine Study), Perth, Western Australia. SUBJECTS: Adolescents (n 1631)
      aged 14 years from a pregnancy cohort study. RESULTS: Factor analysis identified
      two distinct dietary patterns that differed predominantly in fat and sugar
      intakes. The 'Western' pattern consisted of high intakes of take-away foods, soft
      drinks, confectionery, French fries, refined grains, full-fat dairy products and
      processed meats. The 'healthy' pattern included high intakes of whole grains,
      fruit, vegetables, legumes and fish. ANOVA showed that the 'Western' dietary
      pattern was positively associated with greater television viewing and having a
      parent who smoked, and was inversely associated with family income. The 'healthy'
      pattern was positively associated with female gender, greater maternal education,
      better family functioning and being in a two-parent family, and was inversely
      associated with television viewing. CONCLUSIONS: The study suggests that both
      lifestyle factors and family psycho-social environment are related to dietary
      patterns in Australian adolescents.

PMID- 19161649
TI  - A randomized behavioural trial targeting glycaemic index improves dietary, weight
      and metabolic outcomes in patients with type 2 diabetes.
AB  - OBJECTIVE: Glycaemic index (GI) reflects the postprandial glucose response of
      carbohydrate-containing foods. A diet with lower GI may improve glycaemic control
      in people with diabetes. The purpose of the present study was to evaluate the
      change in outcomes following a behavioural intervention which promoted lower-GI
      foods among adults with diabetes. DESIGN: A pre-test-post-test control group
      design was used with participants randomly assigned to an immediate
      (experimental) or delayed (control) treatment group. The intervention included a
      9-week, group-based intervention about carbohydrate and the glycaemic index.
      Dietary, anthropometric and metabolic measures were obtained pre/post
      intervention in both groups and at 18-week follow-up for the immediate group.
      SETTING: The study was conducted in a rural community in the north-eastern USA.
      SUBJECTS: Adults having type 2 diabetes mellitus for > or =1 year, aged 40-70
      years and not requiring insulin therapy (n 109) were recruited. RESULTS:
      Following the intervention, mean dietary GI (P < 0.001), percentage of energy
      from total fat (P < 0.01) and total dietary fibre (P < 0.01) improved in the
      immediate compared with the delayed group. Mean BMI (P < 0.0001), fasting plasma
      glucose (P = 0.03), postprandial glucose (P = 0.02), fructosamine (P = 0.02) and
      insulin sensitivity factor (P = 0.04) also improved in the immediate group
      compared with the delayed group. Mean waist circumference among males (P < 0.01)
      and body weight among males and females (P < 0.01) were significantly different
      between treatment groups. CONCLUSIONS: Educating clients about carbohydrate and
      the glycaemic index can improve dietary intake and health outcomes among adults
      with type 2 diabetes.

PMID- 19161650
TI  - Development of a U.S. EPA drinking water method for the analysis of selected
      perfluoroalkyl acids by solid-phase extraction and LC-MS-MS.
AB  - A drinking water method for perfluoroalkyl acids (PFAAs) is presented that
      addresses the occurrence monitoring needs of the U.S. Environmental Protection
      Agency (EPA) for a future unregulated contaminant monitoring regulation (UCMR).
      This paper describes the challenges associated with developing an analytical
      method for 14 PFAAs that will be used for drinking water occurrence monitoring.
      The method employs solid-phase extraction with analysis by liquid chromatography
      tandem mass spectrometry (LC-MS-MS). The final method preservation scheme
      requires that samples be stored in polypropylene bottles and that they be
      buffered and free chlorine removed with Trizma buffer. Mean recoveries of
      chlorinated surface water samples fortified with the PFAAs at 40-100 ng/L (except
      for the perfluorooctane-sulfonamido-acetic acids at 200 ng/L) are 85-112% with <
      5% relative standard deviation. Single laboratory minimum reporting limits of 2.9
      14 ng/L are demonstrated with this methodology. The final method meets all of the
      EPA UCMR survey requirements for sample collection and storage, precision,
      accuracy, and sensitivity and is expected to be proposed for use under a future
      UCMR.

PMID- 19161651
TI  - Automated solid-phase extraction approaches for large scale biomonitoring
      studies.
AB  - The main value in measuring environmental chemicals in biological specimens
      (i.e., biomonitoring) is the ability to minimize risk assessment uncertainties.
      The collection of biomonitoring data for risk assessment requires the analysis of
      a statistically significant number of samples from subjects with a significant
      prevalence of detectable internal dose levels. This paper addresses the practical
      laboratory challenges that arise from these statistical requirements: development
      of high throughput techniques that can handle, with high accuracy and precision,
      a large number of samples and can do a trace level analysis of multiple and
      diverse environmental chemicals (i.e., analytes). We review here examples of high
      throughput, automated solid-phase extraction methods developed in our laboratory
      for biomonitoring of analytes with representative hydrophobic properties and for
      typical biomonitoring matrices. We discuss key aspects of sample preparation,
      column, and solvent selection for off- and online extractions, and the so-called
      nuts-and-bolts of online column-switching systems necessary for developing-with
      minimal sample handling-rugged, automated methods.

PMID- 19161652
TI  - Trace analysis of polar pharmaceuticals in wastewater by LC-MS-MS: comparison of
      membrane bioreactor and activated sludge systems.
AB  - In order to assess the efficiency of wastewater treatment plants in removing
      pharmaceuticals from wastewater, sensitive and reliable methods are necessary for
      trace analysis of these micropollutants in the presence of a highly complex
      matrix. In this study, conventional activated sludge (CAS) and membrane
      bioreactor (MBR) treatment systems are compared in eliminating pharmaceuticals in
      wastewater. The pharmaceuticals investigated include aceclofenac, carbamazepine,
      diclofenac, enalapril, and trimethoprim. Analysis is performed using a liquid
      chromatograph with hybrid linear ion-trap mass spectrometer equipped with a polar
      reversed-phase column to achieve good separation and minimize matrix effects. To
      pre-concentrate the samples, the use of two types of solid-phase extraction
      packing materials in tandem assures good recoveries of all the target analytes.
      In the influent, the concentration of these compounds ranges from 0.09 to 1.4
      microg/L. Diclofenac shows resistance to degradation in the CAS but is amenable
      to degradation in the MBR. Trimethoprim and enalapril are only slightly
      eliminated in the CAS but are reduced by more than 95% in the MBR. Carbamazepine
      removal is negligible, while aceclofenac is only 50% reduced in CAS and MBR. In
      general, these results indicate that MBR has a higher efficiency in removing some
      polar pharmaceuticals in wastewater.

PMID- 19161653
TI  - On-line purge and trap GC-MS for monitoring 1,3-dichloropropene in agricultural
      water and soil samples.
AB  - A simple and reliable method using on-line purge and trap gas chromatography mass
      spectrometry has been developed for the determination of the fumigant 1,3
      dichloropropene (1,3-DCP) in agricultural water and soil samples. The proposed
      analytical methodology was validated in the target environmental matrices by the
      analysis of spiked blank matrix samples. Limit of detection values of 0.05
      microg/L for water and 0.005 microg/Kg for soils were obtained, while limits of
      quantitation were of 0.1 microg/L for water and 0.01 mg/kg for soils. Good
      recoveries (93-104%) and precision values (< 6%) were obtained for the target
      compound in the studied matrices. This methodology has been successfully applied
      to the analysis of incurred groundwater samples from an agricultural area, The
      Campo de Dalias (Almeria, South Spain), although 1,3-DCP was not detected. The
      method was also applied to soil samples from greenhouse treated with a soil
      fumigant containing 1,3-DCP.

PMID- 19161654
TI  - Method development for the analysis of 1,4-dioxane in drinking water using solid
      phase extraction and gas chromatography-mass spectrometry.
AB  - 1,4-Dioxane has been identified as a probable human carcinogen and an emerging
      contaminant in drinking water. The United States Environmental Protection
      Agency's (U.S. EPA) National Exposure Research Laboratory (NERL) has developed a
      method for the analysis of 1,4-dioxane in drinking water at ng/L concentrations.
      The method consists of an activated carbon solid-phase extraction of 500-mL or
      100-mL water samples using dichloromethane as the elution solvent. The extracts
      are analyzed by gas chromatography-mass spectrometry (GC-MS) in selected ion
      monitoring (SIM) mode. In the NERL laboratory, recovery of 1,4-dioxane ranged
      from 94-110% in fortified laboratory reagent water and recoveries of 96-102% were
      demonstrated for fortified drinking water samples. The relative standard
      deviations for replicate analyses were less than 6% at concentrations exceeding
      the minimum reporting level.

PMID- 19161655
TI  - Analysis of new generation explosives in the presence of u.s. EPA method 8330
      energetic compounds by high-performance liquid chromatography.
AB  - U.S. EPA Method 8330 was evaluated and modified for the analysis of DNAN (2,4
      dinitroanisole) and MNA (n-methyl-p-nitroaniline) by high-performance liquid
      chromatography in various aqueous media in the presence and absence of the 14
      energetic compounds currently assigned to the method. DNAN and MNA are two of the
      four components in PAX-21, a new generation explosive formulation. An optimized
      method was developed to separate all 14 energetic compounds from DNAN and MNA
      using a tertiary mobile phase of water-methanol-acetonitrile (68:28:4) in an
      isocratic run of 35 min. The limit of detection (LOD, 3S(0)) was calculated to be
      10 ppb for both MNA and DNAN. The limit of quantitation (LOQ, 10S(0)) was 40 ppb
      for both compounds. The dynamic ranges for the two compounds were very wide, a
      nearly 5 orders of magnitude range from 0.02 to 1,000 parts per million (ppm).
      The spike recoveries of MNA and DNAN in environmental matrix samples were
      excellent for DNAN, from 87% to 113%. For MNA, the recoveries were slightly high
      at the low level (60 ppb), probably due to some contamination in the ditch and
      pond matrices; but they were satisfactory at higher levels ranging from 85% to
      121%.

PMID- 19161656
TI  - Evaluation of derivatization strategies for the comprehensive analysis of
      endocrine disrupting compounds using GC/MS.
AB  - The expanding list of endocrine disrupting compounds (EDCs) has increased the
      need for the development of improved monitoring methods to evaluate exposure.
      Furthermore, the diverse physiochemical properties of EDCs impose inherent
      analytical limitations, and, thus, a new comprehensive method that can
      simultaneously analyze numerous EDCs in one chromatographic analysis would be a
      significant improvement over current EDC detection methods. Gas
      chromatography/mass spectrometry (GC/MS) offers promising profiling capabilities;
      however, many polar EDCs require derivatization for adequate detection. Here, a
      novel method for the comprehensive profiling of EDCs that employs a silyl
      derivatization strategy to expand the polarity range of compounds able to be
      separated and detected in a single chromatographic analysis is presented. The
      comprehensive method successfully separates 21 GC-ready and 12 derivatization
      required EDCs in one chromatographic analysis. Thermal and microwave
      derivatization methods are effective for a comprehensive EDC mixture, although
      the microwave derivatization often proves more effective in shorter analysis
      time. A pilot-study of spiked surface water from Lake Apopka (Florida)
      demonstrates the potential of the comprehensive EDC profiling method.

PMID- 19161657
TI  - Investigation of HPLC-MS using a monolithic column to separate a diverse suite of
      steroids.
AB  - A rapid method for profiling steroids with a wide range of polarity has been
      developed using high-performance liquid chromatography-mass spectrometry with a
      monolithic LC column. Steroids are detected using tandem mass spectrometry
      (MS(n)) with a quadrupole ion trap and quantified using testosterone-d(3) as the
      internal standard. The method is compared to two similar methods using a
      traditional particulate column in terms of number of steroids eluted, peak area
      reproducibility, limits of detection, and overall analysis time. The monolithic
      method elutes the steroids in a 20-min analysis time, whereas the particulate
      methods elute the steroids in 30 and 45 min, respectively. The monolithic column
      also allows for improved reproducibility (relative standard deviations from 5
      23%, as opposed to 14-42% for the shorter particulate method) and lower limits of
      detection (typically 2-5 times lower) when compared to the particulate column.
      Finally, the method is evaluated with unextracted, spiked alligator plasma,
      giving responses within 80-90% of those expected for standards for all steroids
      tested (except androstenedione).

PMID- 19161658
TI  - The Use of MIMS-MS-MS in field locations as an on-line quantitative environmental
      monitoring technique for trace contaminants in air and water.
AB  - Membrane introduction mass spectrometry (MIMS) is emerging as an important
      technique for on-line, real-time environmental monitoring. Because MIMS
      interfaces are simple and robust, they are ideally suited for operation in MS
      instrumentation used for in-field applications. We report the use of an on-line
      permeation tube to continuously infuse an isotopically labeled internal standard
      for continuous quantitative determinations in atmospheric and aqueous samples
      without the need for off-line calibration. This approach also provides important
      information on the operational performance of the analytical system during multi
      day deployments. We report measured signal stability during on-line deployments
      in air and water of 7% based on variation of the internal standard response and
      have used this technique to quantify BTEX (benzene, toluene, ethylbenzenes, and
      xylenes), pinenes, naphthalene and 2-methoxyphenol (guaiacol) in urban air plumes
      at parts-per-billion by volume levels. Presented are several recent applications
      of MIMS-MS-MS for on-line environmental monitoring in atmospheric and aqueous
      environmental samples demonstrating laboratory, remote and mobile deployments. We
      also present the use of a thermally assisted MIMS interface for the direct
      measurement of polyaromatic hydrocarbons, alkylphenols, and other SVOCs in the
      low ppb range in aqueous environmental samples and discuss improvements in both
      the sensitivity and response times for selected SVOCs. The work presented in this
      paper represents significant improvements in field deployable mass spectrometric
      techniques, which can be applied to direct on-site analytical measurements of VOC
      and SVOCs in environmental samples.

PMID- 19161659
TI  - Determination of ten haloacetic acids in drinking water using high-performance
      and ultra-performance liquid chromatography-tandem mass spectrometry.
AB  - Haloacetic acids (HAAs) are a class of byproducts resulting from the reaction of
      chlorinated disinfectants with natural organic matter. These chemicals have been
      found in animal studies to possibly influence hepatic, reproductive, and
      developmental functions, and they may be mutagenic and carcinogenic. Because HAAs
      are hydrophilic and strongly acidic, it is a challenge to measure them at low
      levels. In this study, nine traditional HAAs and monoiodoacetic acid, an emerging
      disinfection byproduct, are analyzed in water directly. HAAs were separated on a
      BetaMax Acid column or a HILIC UPLC column, and they were detected by negative
      electrospray ionization-tandem mass spectrometry. Although the on-column limits
      of detection of HAAs were lower when using an HILIC UPLC column (0.08-2.73
      microg/L) than when using a BetaMax Acid column (0.18 to 71.5 microg/L), to use
      an HILIC UPLC column, it was required to dissolve water samples in 90%
      acetonitrile before injection and result in sample dilution. BetaMax Acid column
      was found to be more suitable for the analysis of HAAs in drinking water because
      there was no need of sample preparation. Major species of HAAs, such as
      dichloroacetic acid and trichloroacetic acid, and other primary species (e.g.,
      dibromoacetic acid, bromochloroacetic acid and bromodichloroacetic acid) can be
      detected using the BetaMax Acid column at concentrations higher than 1-3
      microg/L.

PMID- 19161660
TI  - Multidimensional GC-fourier transform ion cyclotron resonance MS analyses:
      utilizing gas-phase basicities to characterize multicomponent gasoline samples.
AB  - Hydrocarbon isomers, present in crude petroleum, may yield similar gas
      chromatography (GC) retention times and indistinguishable mass spectral patterns.
      Hence, conventional GC-mass spectrometry (MS) may not provide sufficient data for
      identification of hydrocarbon isomers. Real-time proton affinity or gas-phase
      basicity "bracketing" provides an additional dimension to GC-MS analyses. Our GC
      fourier transform (FT)-ion cyclotron resonance (ICR)-MS yielded an average mass
      measurement error of less than 3 ppm for components of a retail gasoline sample.
      The combined use of concurrent thermo-chemical measurements with GC-FT-ICR-MS
      data analysis allowed differentiation of various isomers such as C(8)H(10)
      species.

PMID- 19161661
TI  - The analysis of halogenated flame retardants by GC-HRMS in environmental samples.
AB  - The analytical conditions required to determine polybrominated diphenylethers
      (PBDEs) and a variety of other halogenated flame retardants (HFRs) by gas
      chromatography-high resolution mass spectrometry (HRMS) in environmental samples
      are reported. HRMS can be used to analyze brominated diphenylethers (BDEs),
      2,2',4,4',5,5'-hexabromobiphenyl (BB-153) as well as for a number of other
      emerging HFRs like allyl 2,4,6-tribromophenyl ether (ATE), 2-bromoallyl 2,4,6
      tribromophenyl ether (BATE), 2,3-dibromopropyl 2,4,6-tribromophenyl ether (DPTE),
      octabromotrimethylphenylindane (OBIND), pentabromoethylbenzene (PBEB),
      hexabromobenzene (HBB), 1,2-bis (2,4,6-tribromophenoxy) ethane (BTBPE),
      decabromodiphenylethane (DBDPE), Dechlorane Plus (DP), hexachlorocyclopentadienyl
      dibromocyclooctane (HCDBCO), tetrabromoethylcyclohexane (TBECH), 1,2,5,6
      tetrabromocylcooctane (TBCO), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTeBB),
      and bis(2-ethly-1-hexyl)tetrabromophthalate (BEHTBP). The detection in
      environmental matrices and use of these non-BDE flame retardants is reviewed. A
      method for the analysis of PBDEs by isotope dilution HRMS and 16 other
      halogenated compounds primarily used as flame retardants is reported. A survey of
      selected environmental samples, which included Lake Ontario surface and tributary
      sediments, municipal wastewater effluent, sludge, and mussel tissues, detected
      PBDEs, DP, DBDPE, BTBPE, PBEB, BB-153, and HBB.

PMID- 19161662
TI  - Identification of N-nitrosamines in treated drinking water using nanoelectrospray
      ionization high-field asymmetric waveform ion mobility spectrometry with
      quadrupole time-of-flight mass spectrometry.
AB  - We report a nanoelectrospray ionization (nESI) with high-field asymmetric
      waveform ion mobility spectrometry (FAIMS) and tandem mass spectrometry (MS-MS)
      method for determination of small molecules of m/z 50 to 200 and its potential
      application in environmental analysis. Integration of nESI with FAIMS and MS-MS
      combines the advantages of these three techniques into one method. The nESI
      provides efficient sample introduction and ionization and allows for collection
      of multiple data from only microliters of samples. The FAIMS provides rapid
      separation, reduces or eliminates background interference, and improves the
      signal-to-noise ratio as much as 10-fold over nESI-MS-MS. The tandem quadrupole
      time-of-flight MS detection provides accurate mass and mass spectral measurements
      for structural identification. Characteristics of FAIMS compensation voltage (CV)
      spectra of seven nitrosamines, N-nitrosodimethylamine (NDMA), N
      nitrosomethylethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n
      propylamine (NDPA), N-nitrosodi-n-butylamine (NDBA), N-nitrosopiperidine (NPip),
      and N-nitrosopyrrolidine (NPyr), were analyzed. The optimal CV of the
      nitrosamines (at DV -4000 V) were: -1.6 V, NDBA; 2.6 V, NDPA; 6.6 V, NPip; 8.8 V,
      NDEA; 13.2 V, NPyr; 14.4 V, NMEA; and 19.4 V, NDMA. Fragmentation patterns of the
      seven nitrosamines in the nESI-FAIMS-MS-MS were also obtained. The specific CV
      and MS-MS spectra resulted in positive identification of NPyr and NPip in a
      treated water sample, demonstrating the potential application of this technique
      in environmental analysis.

PMID- 19161663
TI  - Normalization of urinary drug concentrations with specific gravity and
      creatinine.
AB  - Excessive fluid intake can substantially dilute urinary drug concentrations and
      result in false-negative reports for drug users. Methods for correction
      ("normalization") of drug/metabolite concentrations in urine have been utilized
      by anti-doping laboratories, pain monitoring programs, and in environmental
      monitoring programs to compensate for excessive hydration, but such procedures
      have not been used routinely in workplace, legal, and treatment settings. We
      evaluated two drug normalization procedures based on specific gravity and
      creatinine. These corrections were applied to urine specimens collected from
      three distinct groups (pain patients, heroin users, and marijuana/ cocaine
      users). Each group was unique in characteristics, study design, and dosing
      conditions. The results of the two normalization procedures were highly
      correlated (r=0.94; range, 0.78-0.99). Increases in percent positives by specific
      gravity and creatinine normalization were small (0.3% and -1.0%, respectively)
      for heroin users (normally hydrated subjects), modest (4.2-9.8%) for pain
      patients (unknown hydration state), and substantial (2- to 38-fold increases) for
      marijuana/cocaine users (excessively hydrated subjects). Despite some
      limitations, these normalization procedures provide alternative means of dealing
      with highly dilute, dilute, and concentrated urine specimens. Drug/metabolite
      concentration normalization by these procedures is recommended for urine testing
      programs, especially as a means of coping with dilute specimens.

PMID- 19161664
TI  - Quantification of saxitoxin and neosaxitoxin in human urine utilizing isotope
      dilution tandem mass spectrometry.
AB  - Saxitoxin and neosaxitoxin are potent neurotoxins that can cause paralytic
      shellfish poisoning when consumed. A new assay is presented here to quantify
      saxitoxin (STX) and neosaxitoxin (NEO) in human urine samples. Sample preparation
      of 500-microL samples included the use of weak-cation-exchange solid-phase
      extraction in a multiplexed 96-well format. Extracts were preconcentrated and
      analyzed via 10-min hydrophilic interaction liquid chromatography followed by
      electrospray ionization. Protonated molecular ions were quantified via multiple
      reaction monitoring mode in a Qtrap mass spectrometer. The method uses novel 15N7
      isotopically enriched STX and NEO internal standards. Method validation included
      the characterization of two enriched urine pools. The lowest reportable limits
      for STX and NEO were 4.80 and 10.1 ng/mL, respectively, using both quantification
      and confirmation ions. These two toxins were not detected in a reference range of
      humans who consumed seafood in the preceding 72 h, suggesting that few false
      positives would occur when trying to identify people exposed to STX or NEO.

PMID- 19161665
TI  - Postmortem tissue concentrations of olanzapine.
AB  - Twenty-eight cases from 2004-2007 involving olanzapine were analyzed at the San
      Diego County Medical Examiner's Office. Olanzapine was initially detected by gas
      chromatography coupled with mass spectrometry (GC-MS), and then confirmed by GC
      with a nitrogen-phosphorus detector. In cases where olanzapine was detected,
      concentrations in peripheral blood (PB), central blood (CB), liver, and vitreous
      were determined if available. In the six olanzapine-only deaths, average
      olanzapine concentrations (mean+/-standard deviation) were 3.2+/-2.0 mg/L (PB),
      4.5+/-2.6 mg/L (CB), 40+/-29 mg/kg (liver), and 1.6+/-0.50 mg/L (vitreous). This
      was compared to the 10 non-olanzapine-related deaths, which showed average
      olanzapine concentrations of 0.26+/-0.13 mg/L (PB), 0.29+/-0.17 mg/L (CB), 5.6+/
      5.6 mg/kg (liver), and 0.24+/-0.38 mg/L (vitreous). The remaining 10 multi-drug
      deaths had average concentrations of 0.59+/-0.33 mg/L (PB), 0.64+/-0.60 mg/L
      (CB), 5.9+/-4.3 mg/kg (liver), and 0.78+/-0.91 mg/L (vitreous). Concentrations of
      olanzapine associated with toxicity were found to be in the range of 1.4-6.2 mg/L
      (PB), 1.1-7.4 mg/L (CB), 14-88 mg/kg (liver), and 1.1-2.1 mg/L (vitreous).
      Concentrations associated with therapeutic use were found to be in the range of
      0.11-0.43 mg/L (PB), 0-0.53 mg/L (CB), 0-8.6 mg/kg (liver), and 0-0.98 mg/L
      (vitreous). Deaths attributed solely to olanzapine were distinguished by a 10
      fold or more increase in tissue concentrations over those found in the non
      olanzapine-related deaths.

PMID- 19161666
TI  - Quantitative determination of caffeine and alcohol in energy drinks and the
      potential to produce positive transdermal alcohol concentrations in human
      subjects.
AB  - The purpose of this study was to determine whether non-alcoholic energy drinks
      could result in positive "alcohol alerts" based on transdermal alcohol
      concentration (TAC) using a commercially available electrochemical monitoring
      device. Eleven energy drinks were quantitatively assayed for both ethanol and
      caffeine. Ethanol concentrations for all of the non-alcoholic energy drinks
      ranged in concentration from 0.03 to 0.230% (w/v) and caffeine content per 8-oz
      serving ranged from 65 to 126 mg. A total of 15 human subjects participated in
      the study. Subjects consumed between 6 and 8 energy drinks over an 8-h period.
      The SCRAM II monitoring device was used to determine TACs every 30 min before,
      during, and after the study. None of the subjects produced TAC readings that
      resulted in positive "alcohol alerts". TAC measurements for all subjects before,
      during and after the energy drink study period (16 h total) were <0.02% (w/v).
      Subjects in the study consumed a quantity of non-alcoholic energy drink that
      greatly exceeds what would be considered typical. Based on these results, it
      appears that energy drink consumption is an unlikely explanation for elevated
      TACs that might be identified as potential drinking episodes or "alcohol alerts"
      using this device.

PMID- 19161667
TI  - Gas chromatography-mass spectrometry designation and prediction of metabolic
      dealkylation and hydroxylation reactions in xenobiotics exemplified by tramadol.
AB  - Metabolic dealkylation and hydroxylation reactions in xenobiotics are common and
      may take place at different sites in the molecules. Sometimes confusion may arise
      as to the nature and site of the resulting metabolic change when there is more
      than one potential site. The use of GC-MS in resolving the problem has been
      demonstrated by using tramadol as example. Human urine samples containing
      tramadol and its metabolites were extracted under basic pH conditions and
      analyzed by GC-MS, in the electron impact and chemical ionization modes, before
      and after trimethylsilyl (TMS) derivatization. By recognizing the mass-to-charge
      ratios of molecular and base-peak ions in the mass spectra, it was possible to
      predict and designate sites of demethylation and hydroxylation in tramadol
      metabolites. In addition to the designation of the known tramadol metabolites,
      the practice has led to the tentative characterization of hydroxytramadol and
      norhydroxytramadol as new metabolites of tramadol in humans. Possible extension
      of the modus operandi to other xenobiotics was discussed.

PMID- 19161668
TI  - Screening, quantification, and confirmation of phenylbutazone and oxyphenbutazone
      in equine plasma by liquid chromatography-tandem mass spectrometry.
AB  - A sensitive liquid chromatographic-tandem mass spectrometric method was developed
      and validated for screening, quantification, and confirmation of phenylbutazone
      and oxyphenbutazone in equine plasma. Analytes were recovered from plasma by
      liquid-liquid extraction followed by separation in a reversed-phase column and
      identification by mass spectrometry with selected reaction monitoring in negative
      electrospray ionization mode. Extraction recovery for both analytes was >80%.
      Limits of detection, quantification, and confirmation for both analytes were 0.01
      microg/mL (S/N>or= 3), 0.05 microg/mL, and 0.05 microg/mL, respectively. The
      assay with d9-labeled phenylbutazone as internal standard (IS) was linear over a
      range of 0.05-20 microg/mL (r2>0.995). Intra- and interday precision in terms of
      coefficient of variation was less than 15%. Intra- and interday accuracy (bias%)
      was within 80-120%. Hemolysis of red blood cells decreased analyte signal
      intensity but did not affect quantification results because an isotope-labeled IS
      was used. Analytes were stable in plasma for 24 h at room temperature, 9 days at
      4 degrees C, and 45 days at -20 degrees C and -70 degrees C. The method was
      successfully used in screening, quantification, and confirmation of
      phenylbutazone in post-competition plasma samples obtained from racehorses. The
      method is simple, rapid, and reliably reproducible.

PMID- 19161669
TI  - Stabilization of urinary THC solutions with a simple non-ionic surfactant.
AB  - To stabilize urinary solutions against adsorptive loss of metabolites of Delta9
      tetrahydrocannabinol (THC), a non-ionic surfactant, Tergitol, was investigated to
      reduce the need for special handling and storage of such solutions. Addition of
      surfactant up to 20 times the critical micelle concentration (CMC) did not
      adversely affect the analytical process. Yet, at only two times CMC, surfactant
      was found to mitigate adsorptive loss of THC analytes under a variety of storage
      and handling conditions including exposure to glass and plastic surfaces, after
      storage in a refrigerator or freezer, and at reduced pH, where adsorptive losses
      were expected to be significant. On average, micellar solubilization of analyte
      increased the assayed concentration by 10% with a range of 3 to 20%, depending on
      condition, relative to solutions without surfactant. Solutions with surfactant
      did not fail (i.e., deviate in concentration by +/-20%) over a 49-week period,
      whereas those without surfactant failed by 21 weeks. These results indicate that
      addition of small amounts of non-ionic surfactant to solutions of urinary THC
      metabolites is a simple method to improve both the accuracy and precision of
      analyte concentrations, as determined by gas chromatography-mass spectrometry, in
      such solutions by mitigating adsorptive losses during storage and handling
      events.

PMID- 19161670
TI  - Confirmation of gelsemium poisoning by targeted analysis of toxic gelsemium
      alkaloids in urine.
AB  - The gelsemium plants are highly poisonous but toxicological evaluation of
      suspected poisoning cases has been hampered by the chemical complexity of the
      gelsemium toxins involved. A novel liquid chromatography-tandem mass spectrometry
      protocol was optimized for the collective detection of gelsemine and related
      alkaloids from Gelsemium elegans. The screening protocol was applied to the
      clinical investigation of unexplained intoxications following the ingestion of
      seemingly nontoxic herbs. In three clusters of toxicological emergencies ranging
      from severe dizziness to respiratory failure, Gelsemium elegans mistaken for
      various look-alike therapeutic herbs was suspected to be the hidden cause of
      poisoning. Nine cases of gelsemium poisonings were thus ascertained by the
      diagnostic urine alkaloid profiles. Gelsemine was sustained as the main urinary
      marker of Gelsemium exposure.

PMID- 19161671
TI  - Fatal fluoxetine intoxication with markedly elevated central blood, vitreous, and
      liver concentrations.
AB  - Since being introduced into clinical practice 20 years ago, fluoxetine, a
      serotonin-reuptake inhibitor, has remained one of the most popular
      antidepressants prescribed in the United States. Upon reviewing the literature,
      the highest reported postmortem central blood fluoxetine and norfluoxetine
      concentrations are 22 and 6.8 mg/L, respectively, and reported liver fluoxetine
      and norfluoxetine concentrations are 29-128 and 17 mg/kg, respectively. A 31-year
      old female with convulsive activity was found at home by her husband. Emergency
      services was contacted, and responders found the patient unresponsive with agonal
      respirations, a pulse of 20 bpm, and no measurable blood pressure. Despite all
      resuscitative efforts, the patient expired. Postmortem analyses revealed
      concentrations of 33 mg/L fluoxetine and 12 mg/L norfluoxetine in central blood
      and 400 mg/kg fluoxetine and 460 mg/kg norfluoxetine in liver. Vitreous
      fluoxetine and norfluoxetine concentrations were 5.2 and 2.2 mg/L, respectively.
      Utilizing a sensitive and specific analytical procedure, we report the highest
      recorded central blood and liver fluoxetine and norfluoxetine concentrations.

PMID- 19161672
TI  - Does vitamin C deficiency result in impaired brain development in infants?
AB  - Scurvy, the rare but potentially mortal manifestation of severe and prolonged
      lack of vitamin C, is often confused with hypovitaminosis C, i.e. the mere
      definition of vitamin C deficiency. While the latter condition can be diagnosed
      in millions, the clinical consequences (if they exist) remain largely unknown,
      since only a tiny fraction of those deficient in vitamin C actually develop
      clinical scurvy. Is hypovitaminosis C itself a problem at all then? Yes, it may
      well be in some cases. Recent data from our laboratory suggest that the neonatal
      brain is particularly susceptible to vitamin C deficiency and that this condition
      may adversely affect early brain development.

PMID- 19161673
TI  - Effect of Piper betle on plasma antioxidant status and lipid profile against D
      galactosamine-induced hepatitis in rats.
AB  - Betle leaf chewing is an old traditional practice in India and other countries of
      East Asia. We have investigated the antioxidant and antihyperlipidaemic potential
      of an alcoholic leaf-extract of Piper betle against D-galactosamine (D-GalN; 400
      mg/kg body weight, i.p. single dose) intoxication in male albino Wistar rats.
      Rats were treated with leaf-extract (200 mg/kg body weight) by intragastric
      intubations daily for 20 days. The animals were divided randomly into five groups
      of six animals each as control, control plus extract, D-GalN control, D-GalN-rats
      on treatment with extract or silymarin, a standard drug. We observed an increase
      in the plasma levels of thiobarbituric acid reactive substances (TBARS), lipid
      hydroperoxides, and a decrease in vitamin C, vitamin E and reduced glutathione
      concentrations. Very low density lipoprotein cholesterol and low density
      lipoprotein cholesterol increased significantly while high density lipoprotein
      cholesterol decreased. Further, increase in the levels of total cholesterol,
      phospholipids, triglycerides, free fatty acids in the plasma and tissues of liver
      and kidney were observed in D-GalN-treated rats. Administration of P. betle leaf
      extract prevented the increase or decrease of these parameters and brought
      towards normality. These results suggest that P. betle could afford a significant
      antioxidant and antihyperlipidaemic effect against D-GalN-intoxication.

PMID- 19161674
TI  - N-Acetyl cysteine restores viability and function of rat odontoblast-like cells
      impaired by polymethylmethacrylate dental resin extract.
AB  - There is concern that dental-resin materials directly loaded on a prepared tooth
      adversely affect dental pulp tissue by releasing the resin chemicals through
      dentinal tubes. This study determined whether self-curing polymethyl methacrylate
      (PMMA)-based dental resin extract adversely affected the viability and function
      of odontoblast-like cells and whether the cytotoxicity of this resin, if any,
      could be eliminated by N-acetyl cysteine, an antioxidant amino acid derivative.
      Odontoblast-like cells isolated from rat maxillary incisor dental pulp tissue
      were exposed to a PMMA resin extract with or without N-acetyl cysteine for 1 h
      and then cultured in osteoblastic media. The percentage of viable cells 24 h
      after seeding was 20% in cells exposed to the resin extract without N-acetyl
      cysteine, whereas 45% of cells were viable after exposure to the N-acetyl
      cysteine-supplemented extract. The cells that had been exposed to the extract
      showed a strong tendency for apoptosis associated with the increased reactive
      oxygen species production and decreased intracellular glutathione level, which
      was improved by the addition of N-acetyl cysteine. N-Acetyl cysteine
      supplementation almost completely restored the significantly reduced alkaline
      phosphatase activity and matrix mineralization by the resin extract. These
      results conclusively demonstrated that exposure of odontoblast-like cells to the
      resin extract impaired the cell viability and function and, more intriguingly, N
      acetyl cysteine supplementation to the extract significantly prevented these
      toxic effects.

PMID- 19161675
TI  - A machine-learning approach to the prediction of oxidative stress in chronic
      inflammatory disease.
AB  - Oxidative stress is implicated in the development of a wide range of chronic
      human diseases, ranging from cardiovascular to neurodegenerative and inflammatory
      disorders. As oxidative stress results from a complex cascade of biochemical
      reactions, its quantitative prediction remains incomplete. Here, we describe a
      machine-learning approach to the prediction of levels of oxidative stress in
      human subjects. From a database of biochemical analyses of oxidative stress
      biomarkers in blood, plasma and urine, non-linear models have been designed, with
      a statistical methodology that includes variable selection, model training and
      model selection. Our data demonstrate that, despite a large inter- and intra
      individual variability, levels of biomarkers of oxidative damage in biological
      fluids can be predicted quantitatively from measured concentrations of a limited
      number of exogenous and endogenous antioxidants.

PMID- 19161676
TI  - Expression of extracellular superoxide dismutase during adipose differentiation
      in 3T3-L1 cells.
AB  - Obesity is known to be the primary causal component in metabolic syndrome.
      Adipocytes in obese patients exhibit increased oxidative stress via the
      activation of reactive oxygen species (ROS)-producing systems and inactivation of
      antioxidant enzymes. Extracellular superoxide dismutase (EC-SOD) is an anti
      inflammatory enzyme that protects cells from the damaging effects of ROS. An
      earlier report showed that plasma EC-SOD levels in type 2 diabetic patients were
      significantly and inversely related to body mass index and homeostasis model
      assessment-insulin resistance index. Moreover, the administration of
      pioglitazone, an antidiabetic agent, significantly increased the plasma level of
      EC-SOD. In this report, the expression of EC-SOD was compared to other
      adipocytokines in mice 3T3-L1 pre-adipocytes. EC-SOD expression levels were
      increased after the induction of differentiation and then declined, which was
      similar to adiponectin and transcription factors such as peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer-binding protein-alpha
      (C/EBP-alpha). On the other hand, the expression levels of pro-inflammatory
      adipocytokines, such as tumor necrosis factor-alpha (TNF-alpha) and monocyte
      chemo-attractant protein-1 (MCP-1), increased markedly in the development stage
      of cells. It was observed that the expression of EC-SOD in differentiated 3T3-L1
      cells co-cultured with LPS-stimulated J774 macrophages was up-regulated, while
      the addition of TNF-alpha down-regulated EC-SOD and adiponectin expression in
      adipocytes. It is known that infiltrated and activated macrophages produce
      extracellular ROS at high levels in adipose tissue. It is possible that the
      expression of EC-SOD in adipocytes was stimulated to protect them from oxidative
      stress in the co-culture system.

PMID- 19161677
TI  - Antioxidant activity of methanolic extract of Bombax ceiba.
AB  - The antioxidant activity of a methanolic extract of Bombax ceiba was evaluated
      using several antioxidant assays, in terms of its: (i) ability to scavenge DPPH
      (1,1-diphenyl-2-picryl-hydrazyl) and hydroxyl free radicals; (ii) action against
      lipid peroxidation (in rat liver microsomes and soy bean phosphatidylcholine
      liposomes), induced by ascorbyl radicals and peroxynitrite; and (iii) effect on
      myeloperoxidase activity. The cytotoxicity was monitored through the
      mitochondrial activity in the Vero cell line. The extract showed antioxidant
      activity in all assays, the EC(50) (microg/ml) for DPPH was 87 and for lipid
      peroxidation of microsomes and soy bean liposomes induced by ascorbyl radicals
      were 141 and 105, respectively, and by peroxynitrite were 115 and 77,
      respectively. The K(0.5) value for myeloperoxidase activity inhibition by the
      extract was 264 microg/ml. The extract showed very low toxicity toward Vero
      cells.

PMID- 19161678
TI  - Ecological study of the larger black flour beetle in cotton gin trash.
AB  - The larger black flour beetle Cynaeus angustus (Leconte) thrives in cotton gin
      trash piles on the Southern High Plains of Texas and sometimes becomes a nuisance
      after invading public and private structures. For better understanding of the
      basic larger black flour beetle ecology in gin trash piles, we conducted a series
      of laboratory and semirealistic field trials. We showed (1) in naturally infested
      gin trash piles, that similar trap captures were obtained in three cardinal
      directions; (2) in a laboratory study, late-instar larvae stayed longer in larval
      stage in moist soil compared with drier soil; (3) in both horizontal and vertical
      choice experiments, late instars preferred soil with low moisture content; and
      (4) specifically larger black flour beetle adults, but most larvae as well,
      responded negatively to high moisture content in gin trash. The results presented
      are consistent with reports of larger black flour beetle living in decaying yucca
      palms in deserts and suggest that maintaining gin trash piles with high moisture
      content may be an important component in an integrated control strategy.

PMID- 19161679
TI  - Modeling embryo development of Sitona discoideus Gyllenhal (Coleoptera:
      Curculionidae) under constant temperature.
AB  - The alfalfa root weevil, Sitona discoideus (Coleoptera: Curculionidae), is an
      important pest of alfalfa. The developmental rates of the embryo development were
      recorded at eight constant temperatures ranging from 8.5 to 30 degrees C. Using
      10 models (1 linear and 9 nonlinear), we evaluated the relationship between
      constant temperature and developmental rate. Embryo development was shortest (8.5
      d) and longest (69 d), at 28 and 8.5 degrees C, respectively. The threshold
      temperature (T0) and the thermal constant (K) were estimated using linear
      regression to be 4.7 degrees C and 207.7 DD, respectively. The two most efficient
      nonlinear models, the Lactin and the Sharp and DeMichele, gave estimates of Tmin
      and Tmax of 4.4 and 3.9 and 30.0 and 30.9 degrees C, respectively. This
      information has potential application in predicting the suitability and optimal
      time of release of an egg parasitoid of S. discoideus.

PMID- 19161680
TI  - Determination of sensitive stage for switching migrant oriental armyworms into
      residents.
AB  - The sensitive stage for switching migrant oriental armyworm, Mythimna separata
      (Walker), into residents was determined under the stresses of starvation and cold
      (5 degrees C) in a laboratory population. Presumed migrants developing from
      gregarious larvae oviposited significantly earlier when adults were starved or
      shocked by cold only during the first 24 h after emergence. In contrast,
      preoviposition periods for migrants starved or cooled on days 2-6 of adult life
      were not significantly affected. The preresponse period of male migrants starved
      on day 1 of adult life was also significantly shortened, whereas those treated on
      following days were not significantly influenced. Similarly, total lifetime
      fecundity of migrants, which were starved or cooled on day 1 after emergence, was
      significantly increased; however, the same effect was not observed in migrants
      that were stressed later. Although preoviposition periods of presumed residents,
      developing from solitary larvae, starved or shocked by cold during the first
      several days of adulthood were significantly prolonged, this delay was not
      related to migratory strategy, because lifetime fecundity was not significantly
      reduced. The results suggest that the first day of adult life in this species is
      a sensitive stage during which migrants can shift into residents, although
      residents cannot shift to migrants. Thus, starvation and cold experienced in this
      stage induces migrants to modify their developmental path into reproduction and
      residency.

PMID- 19161681
TI  - Effects of photoperiod on boll weevil (Coleoptera: Curculionidae) development,
      survival, and reproduction.
AB  - Effects of photoperiod on development, survival, feeding, and oviposition of boll
      weevils, Anthonomus grandis grandis Boheman, were assessed under five different
      photophases (24, 14, 12, 10, and 0 h) at a constant 27 degrees C temperature and
      65% RH in the laboratory. Analyses of our results detected positive relationships
      between photoperiod and puncturing (mean numbers of oviposition and feeding
      punctures per day), and oviposition (oviposition punctures/oviposition+feeding
      punctures) activities, and the proportion of squares attacked by boll weevil
      females. When boll weevil females developed in light:darkness cycles, they
      produced a significantly higher percentage of eggs developing to adulthood than
      those developed in 24-h light or dark conditions. In long photoperiod (24:0 and
      14:10 h), the number of female progeny was significantly higher and their
      development time was significantly shorter than those developed in short
      photoperiod (0:24 and 10:14 h). Lifetime oviposition was significantly highest at
      12- and 14-h photophase, lowest at 0- and 10-h photophase, and intermediate at 24
      h of light. Life table calculations indicated that boll weevil populations
      developed in a photoperiod of 14:10 and 12:12 (L:D) h will increase an average of
      two-fold each generation (Ro) compared with boll weevils developed in 24:0- and
      10:14-h photoperiods and 15-fold compared with those at 0:24 h. Knowledge of the
      photoperiod-dependent population growth potential is critical for understanding
      population dynamics to better develop sampling protocols and timing insecticide
      applications.

PMID- 19161682
TI  - Manuka oil and phoebe oil are attractive baits for Xyleborus glabratus
      (Coleoptera: Scolytinae), the vector of laurel wilt.
AB  - Redbay ambrosia beetle, Xyleborus glabratus Eichhoff, is a native of Southeast
      Asia recently established in coastal forests of Georgia, SC and Florida. It
      vectors a wilt fungus, Raffaelea sp., lethal to redbay trees, Persea borbonia L.
      Spreng, and certain other Lauraceae. No practical monitoring system exists for
      this beetle so we conducted studies to identify host attractants and develop
      lures. Volatiles were collected from redbay wood and bark by steam distillation,
      direct solvent extraction, and dynamic headspace sampling with a Poropak Q
      cartridge. Steam, methanol, and pentane extracts were tested as baits in trapping
      trials but were not attractive to X. glabratus. Major constituents in Poropak
      aerations identified by gas chromatography-mass spectrometry included alpha
      pinene, beta-pinene, delta-3-carene, eucalyptol, p-cymene, alpha-copaene,
      terpinene-4-ol, linalool, calamenene, and nonanoic acid. We assayed several of
      these compounds (including eucalyptol, p-cymene, terpinene-4-ol, linalool,
      nonanoic acid, and caryophyllene oxide) both individually and in combination, but
      none were attractive at tested doses. Two other redbay odor components, alpha
      copaene and calamenene, were unavailable in sufficient quantities commercially so
      we substituted manuka oil, the essential oil extracted from Leptospermum
      scoparium Forst. and Forst., which contains high proportions of both compounds.
      Manuka oil was equally attractive as redbay wood to X. glabratus, but increasing
      release rates >10-fold did not enhance its activity. Phoebe oil, an extract of
      Brazilian walnut (Phoebe porosa Mez.), which contains significant quantities of
      alpha-copaene and calamenene, was also attractive. Fractions of manuka oil were
      not more attractive than the whole oil. Manuka and phoebe oil are readily
      available and are good alternatives to redbay wood as a trap bait for monitoring
      X. glabratus distribution and population trends.

PMID- 19161683
TI  - Field-testing of synthetic herbivore-induced plant volatiles as attractants for
      beneficial insects.
AB  - Seven synthetic herbivore-induced plant volatiles (HIPVs) and a mixture of
      nonanal + (Z)-3-hexen-1-ol were field tested for their ability to attract
      beneficial insects in an open cotton field. Eleven species of the main natural
      enemies of insect pests in cotton fields were studied. Significantly greater
      numbers of the ladybird beetle Coccinella septempunctata were trapped on (Z)-3
      hexenyl acetate-baited cards than on others that were HIPV baited or the control
      cards. Erigonidium graminicolum was attracted to traps baited with nonanal, (Z)-3
      hexenyl acetate, and methyl salicylate (MeSA). The predatory bug Deraeocoris
      punctulatus was only attracted to traps baited with octanal. The predatory bug
      Orius similis responded to traps baited with 3,7-dimethyl,1,3,6-octatriene,
      nonanal, (Z)-3-hexenyl acetate, nonanal + (Z)-3-hexen-1-ol, and MeSA. Dimethyl
      octatriene, nonanal + (Z)-3-hexen-1-ol, and octanal significantly attracted the
      syrphid fly Paragus quadrifasciatus. The ladybird beetle Propylaea japonica, the
      green lacewing Chrysopa sinica, the bigeyed bug Geocoris pallidipennis, the
      syrphid fly Epistrophe balteata, and the parasitic wasp Campoletis chlorideae did
      not respond to any of the HIPVs tested. These results are discussed with regard
      to the potential of HIPVs as tools for recruiting natural enemies into cotton
      fields.

PMID- 19161684
TI  - Behavioral and electroantennographic responses of the tea mosquito, Helopeltis
      theivora, to female sex pheromones.
AB  - Responses of the tea mosquito, Helopeltis theivora (Waterhouse) (Hemiptera:
      Miridae), a major pest of tea, to female sex pheromone compounds were measured
      using wind tunnel and electroantennogram (EAG) bioassays. In the wind tunnel,
      male tea mosquitoes were found to be most attracted to a dichloromethane extract
      of the female thorax. Gas chromatography-mass spectrometry (GC-MS) analysis of
      female thoracic extracts and dynamic head space samples of virgin females showed
      the presence of five compounds: (Z)-3 hexenyl acetate, (Z)-3 hexenyl butanoate,
      (E)-2 hexenyl pentanoate, 2,4 dimethyl pentanal, and (E)-2-hexenol. Male tea
      mosquitoes were attracted to blends of (Z)-3 hexenyl acetate and (E)-2-hexenol in
      the wind tunnel with a 1:5 ratio eliciting the greatest response. EAG recordings
      of male antenna confirmed the ability of this blend to evoke antennal responses
      in male insects. Similarly active EAG responses were recorded toward female
      thoracic extract and a blend of (Z)-3 hexenyl acetate and (E)-2-hexenol.
      Behavioral responses of adult males are mediated by a blend of volatile female
      sex pheromone compounds, (Z)-3 hexenyl acetate and (E)-2-hexenol, at a ratio of
      1:5. This female sex pheromone blend may be useful for tea mosquito control and
      management programs.

PMID- 19161685
TI  - First detection of Wolbachia in arrhenotokous populations of thrips species
      (Thysanoptera: Thripidae and Phlaeothripidae) and its role in reproduction.
AB  - Insects in the order Thysanoptera are known for their haplodiploid reproduction,
      with most species reproducing by arrhenotoky. A few species, however, have only
      female populations and reproduce by thelytoky. Seven thrips species reproducing
      either by arrhenotoky [Frankliniella occidentalis (Pergande), Echinothrips
      americanus Morgan, Suocerathrips linguis Mound and Marullo, Gynaikothrips ficorum
      (Marchal)] or thelytoky [Hercinothrips femoralis (O.M. Reuter) and Parthenothrips
      dracaenae (Heeger)] or showing both reproduction modes (Thrips tabaci Lindeman)
      were screened for the presence of Wolbachia using 16S rDNA and ftsZ gene primers.
      The arrhenotokous reproducing species E. americanus, G. ficorum, and S. linguis
      tested positive for Wolbachia. The bacterium was not detected in F. occidentalis
      or T. tabaci; even the thelytokous population of T. tabaci was free of Wolbachia.
      Wolbachia was found in the thelytokous reproducing species H. femoralis and P.
      dracaenae. Antibiotic treatment of H. femoralis induced the production of males
      that copulated with females. The results confirmed Wolbachia to be present in
      thelytokous reproducing thrips species and proved the presence of the bacterium
      for the first time in some arrhenotokous reproducing thrips species.

PMID- 19161686
TI  - Factors influencing larval survival of the invasive browntail moth (Lepidoptera:
      Lymantriidae) in relict North American populations.
AB  - Scant attention has been paid to invasive species whose range and abundance has
      decreased after an initial range expansion. One such species is the browntail
      moth Euproctis chrysorrhoea L, which was discovered in the eastern United States
      in 1897. Its range expanded until 1914; after 1915, however, its range contracted
      and now it persists in only two isolated coastal locations. Although a biological
      control agent has been implicated in this range collapse, cold inland winter
      temperatures may also help to restrict browntail moth populations. We surveyed
      coastal versus inland habitats in Maine and Massachusetts for browntail moth
      overwintering mortality and larval density per web. We also performed an
      experiment assessing these same variables in coastal versus inland habitats on
      different host plant species and at different initial larval densities. We also
      analyzed temperature records to assess whether winter temperatures correlated
      with changes in the invasive range. Overwintering mortality was lower in coastal
      populations for both the experimental populations and in the Maine field survey.
      Experimental populations in Cape Cod coastal areas also had lower rates of fall
      mortality and higher larval densities, suggesting that coastal areas are better
      year-round habitats than inland areas. There were no consistent differences
      between coastal and inland populations in their response to larval density or
      host plant, although overall survival in both areas was higher at low initial
      larval densities and affected by host identity. There was also no difference in
      two measures of the coldest winter temperatures during browntail moth's expansion
      and contraction. Our results show that climate affects browntail moth, but
      suggest that winter temperatures cannot explain both the rapid expansion and
      subsequent collapse of this pest.

PMID- 19161687
TI  - Patterns of variation in the seasonal dynamics of Listronotus maculicollis
      (Coleoptera: Curculionidae) populations on golf course turf.
AB  - Listronotus maculicollis (Kirby) is a burgeoning pest of Poa annua L. in the
      northeast United States. To develop an understanding of its spatial and temporal
      association with golf course landscapes, we described the patterns of variation
      in certain population parameters across site (Fayetteville and Ithaca, NY), year
      (2004-2006), and management habitat (fairway, intermediaterough, rough). In
      weekly surveys along fairway transects, we sampled larvae (identified to instar)
      by soil core extraction and adults (identified to sex and maturation)by hand
      collection. Five instars were confirmed based on head capsule width measurements;
      there was no overlap among instars. Sex ratio was significantly male-skewed on
      the rough versus the fairway. Insect load, a measure of population size based on
      cumulative insect-days, varied from 3.0- to 18.5-fold across sites and years and
      averaged 8.7- and 8.0-fold greater on the fairway than rough for larvae and
      adults, respectively. Visual assessment of stage-specific population fluctuation
      curves revealed no divergence in adult males and females, i.e., no evidence of
      protandry. Variation was greater by year than by site in terms of overall shape
      of the fluctuation curves, relative abundance of overwintered to spring and
      summer adults, population synchrony, and number of generations (two to three).
      Evidence of bimodal spring generations showed that early season population
      synchrony may be linked to the pattern of adults transitioning from overwintering
      to developmental habitats. The magnitude of variation in population dynamics
      underscores the relevance of decision-making strategies and has implications for
      improving both the spatial and temporal targeting of intervention tactics.

PMID- 19161688
TI  - Emergence and seasonal activity of the entomophagous rove beetle Aleochara
      bilineata (Coleoptera: Staphylinidae) in canola in Western Canada.
AB  - Aleochara bilineata Gyllenhal (Coleoptera: Staphylinidae) is an important natural
      enemy of root maggots (Delia spp.) (Diptera: Anthomyiidae), which are serious
      pests of brassicaceous crops in North America and Europe. Adults of A. bilineata
      feed on eggs and larvae of root maggots, and A. bilineata larvae parasitize Delia
      spp. pupae. Emergence and seasonal activity patterns of A. bilineata were
      investigated during 2003-2005 in canola (Brassica rapa L. and Brassica napus L.)
      in central Alberta, Canada, in relation to degree-day (DD) accumulations and
      Julian date. Captures of A. bilineata adults from pitfall traps within emergence
      cages situated over canola stubble from the previous year indicated that
      approximately 428, 493, and 455 DD (soil base 5.57 degrees C) and 187, 189, and
      180 Julian days were required for 50% emergence in 2003, 2004, and 2005,
      respectively (3-yr mean = 185.1 +/- 2.8 Julian days [SEM]). Captures of A.
      bilineata adults from pitfall traps placed in current canola crops determined
      that 50% levels of activity density required 379 DD and 180 Julian days in 2004.
      A logistic model that described the relationship of degree-days and Julian days
      with emergence of adult beetles was appraised, and good correspondence was
      evident between predicted and observed cumulative emergence patterns. Emergence
      and seasonal activity periods of A. bilineata in canola were well synchronized
      with occurrence of preimaginal life stages of its principal hosts, Delia radicum
      (L.) and Delia platura Meigen, with beetle emergence beginning shortly after the
      onset of root maggot oviposition.

PMID- 19161689
TI  - A comparison of bark and ambrosia beetle communities in two forest types in
      northern Thailand (Coleoptera: Curculionidae: Scolytinae and Platypodinae).
AB  - Many ecological studies of tropical insects are based on small sample sizes or
      lack sampling scheme rigor, which prevents testing ecological hypotheses and
      comparing samples from different sites and times. Here we present the results of
      quantitative trapping of bark and ambrosia beetles over 2 yr at two localities in
      northern Thailand separated by 5 km, 1,100 m in altitude, and in different forest
      types. Beetles were collected using a spatially and temporally standardized
      sampling scheme, followed by a quantitative analysis of community composition and
      its responses to environmental variables and trapping techniques. In total, 118
      species were collected, but the species accumulation curves show little sign of
      leveling off. Based on slightly different species accumulation rates, the more
      humid site has a little higher species richness. Species composition was
      significantly different between the sites, which was not a result of
      undersampling of rare species. alpha diversity at each site contributes to the
      regional diversity more than the turnover of species between the sites (beta
      diversity). Mean annual temperature and humidity have larger effects on the
      community species composition than seasonal fluctuations of temperature and
      humidity at each site--beetles do choose their environment but are aseasonal. The
      site with greater humidity supported significantly more species living in a
      symbiosis with fungi (ambrosia beetles), whereas the drier and more disturbed
      site hosted a greater number of circumtropical colonizer species. Each of the
      different types of trap had a bias for certain taxonomic groups. The results show
      that even modest samples, if properly structured and analyzed, can answer many
      ecological questions and can serve in biodiversity comparisons on broad scales.

PMID- 19161690
TI  - Positive effects of shade and shelter construction by ants on leafhopper-ant
      mutualism.
AB  - The myrmecophilous five-spotted gamagrass leafhopper, Dalbulus quinquenotatus
      DeLong and Nault, and its tending ants on gamagrass Tripsacum dactyloides L. were
      examined to determine the influence of shade and ant-constructed shelters on the
      population sizes of D. quinquenotatus and ants. Gamagrass plants hosting ants and
      leafhoppers were exposed to 50, 30, or 0% artificially constructed shade. The
      greatest numbers of leafhoppers and ants were found on plants that received 50%
      shade. Shelters made by the ant Solenopsis geminata (F.) contained large numbers
      of leafhoppers and ants but were found only on T. dactyloides exposed to 50%
      shade in artificially constructed habitats. Additional sampling was conducted on
      wild gamagrass plants in the field to explore the presence of ants tending
      leafhoppers in shelters and to evaluate whether ant-constructed shelters protect
      leafhopper nymphs from parasitoid wasps. Large aggregations of S. geminata in
      shelters were also found in natural gamagrass habitats. Leafhopper nymphs living
      in shelters made by S. geminata may be protected against the dryinid wasp
      parasitoid Anteon ciudadi Olmi. No sheltered nymphs were parasitized by dryinids,
      whereas 24% of unsheltered nymphs had dryinid parasitism.

PMID- 19161691
TI  - Parasitoids reared from predators of hemlock woolly adelgid (Hemiptera:
      Adelgidae), and the hymenopterous parasitoid community on western hemlock in the
      Pacific Northwest.
AB  - In western North America, infestations of the hemlock woolly adelgid, Adelges
      tsugae Annand (Hemiptera: Adelgidae), are common on orchard, ornamental, and
      roadside western hemlock, Tsuga heterophylla (Raf.) Sargent. However, these
      infestations rarely cause T. heterophylla mortality. Host tolerance and presence
      of endemic predators may be contributing to the relatively low levels of injury
      to T. heterophylla caused by A. tsugae. Field surveys of the arthropod community
      associated with A. tsugae infestations on 116 T. heterophylla at 16 sites in
      Oregon and Washington were conducted every 4-6 wk from January 2005 through
      November 2006. Fourteen uninfested T. heterophylla were also surveyed across 5 of
      the 16 sites. Immature A. tsugae predators collected in the field were brought to
      the laboratory for rearing. Eight species of hymenopterous parasitoids were
      reared from pupae of predators of A. tsugae in the laboratory. Two Pachyneuron
      spp. (Pteromalidae) and a Melanips sp. (Figitidae) were reared from Leucopis spp.
      (Diptera: Chamaemyiidae) puparia. Syrphoctonus pallipes (Gravenhorst)
      (Ichneumonidae), Woldstedtius flavolineatus (Gravenhorst) (Ichneumonidae),
      Syrphophagus sp. (Encyrtidae), and Pachyneuron albutius Walker were reared from
      Syrphidae (Diptera) puparia. A Helorus sp. (Heloridae) was reared from a
      Chrysoperla sp. (Neuroptera: Chrysopidae) cocoon. Laboratory rearing did not show
      any direct association between parasitoids and A. tsugae. In the field survey, a
      total of 509 adult parasitic Hymenoptera representing 19 families and at least 57
      genera were collected from T. heterophylla. Nonparametric analysis of community
      structure showed Pachyneuron spp. were strongly correlated to abundance of their
      Leucopis spp. hosts and to A. tsugae population score in the field. The possible
      impact of parasitism on Leucopis spp., potential A. tsugae biological control
      candidates for the eastern United States, is discussed.

PMID- 19161692
TI  - Diversity patterns in Iberian Calathus (Coleoptera, Carabidae: Harpalinae):
      species turnover shows a story overlooked by species richness.
AB  - We assessed the relationships between diversity patterns of Iberian Calathus and
      current environmental gradients or broad-scale spatial constraints, using 50-km
      grid cells as sampling units. We assessed the completeness of the inventories
      using nonparametric estimators to avoid spurious results based on sampling
      biases. We modeled species richness and beta diversity, using spatial position,
      and 23 topographical, climatic, and geological variables as predictors in
      regression and constrained analysis of principal coordinates modeling.
      Geographical situation does not seem to affect Calathus species richness, because
      no spatial pattern was detected. The environmental variables only explained 23%
      of the variation in richness. Spatial and environmental predictors explained a
      large part of the variation in species composition (58%). The fraction shared by
      both groups of variables was relatively large, but the pure effect of each model
      was still important. Our results show that it is necessary to assess the
      completeness of inventories to avoid drawing false conclusions. Also, Iberian
      Calathus represent a clear example of the need for combined analyses of species
      richness and beta diversity patterns, because the lack of patterns in the former
      does not imply the invariance of biotic communities.

PMID- 19161693
TI  - Propagation, synchrony, and impact of introduced and native Laricobius spp.
      (Coleoptera: Derodontidae) on hemlock woolly adelgid in Virginia.
AB  - Synchrony and impact of the predators Laricobius nigrinus Fender and Laricobius
      rubidus LeConte, on hemlock woolly adelgid, Adelges tsugae Annand, were studied
      in an eastern hemlock field insectary in Virginia. First, a field insectary for
      propagation of the introduced L. nigrinus was established by planting hemlocks in
      2001, infesting them with hemlock woolly adelgid in 2002 and 2003, followed by
      releasing 258 L. nigrinus in 2003. Initial sampling showed that the native L.
      rubidus was present in the area. Hemlock woolly adelgid and both Laricobius
      species populations increased annually, from which 305 F3 L. nigrinus adults were
      collected and redistributed to forests in 2007. Second, the phenology of hemlock
      woolly adelgid and Laricobius spp. life cycles were monitored in 2005 and 2006.
      Adult L. nigrinus (F2) and L. rubidus were active on hemlock from fall through
      mid-spring and overlapped with second-instar sistentes nymphs through
      progredientes eggs. The predators' eggs were oviposited and larvae developed
      (i.e., F3 L. nigrinus) from late winter to mid-spring on progredientes eggs,
      indicating synchrony with suitable prey life stages. Third, a predator exclusion
      experiment was used to examine the relationships between the predators and prey
      in 2005 and 2006. When exposed to L. nigrinus (F2 adults and F3 larvae) and L.
      rubidus, hemlock woolly adelgid survival and ovisac density were lower and ovisac
      disturbance was higher than hemlock woolly adelgid protected in cages. The
      establishment and production of L. nigrinus at a field insectary, synchronization
      with, and impacts on hemlock woolly adelgid after a small release 2 yr earlier
      makes it an important potential biological control agent of hemlock woolly
      adelgid.

PMID- 19161694
TI  - Influence of Prunus spp., peach cultivars, and bark damage on oviposition choices
      by the lesser peachtree borer (Lepidoptera: Sesiidae).
AB  - An examination of oviposition choices by the lesser peachtree borer, Synanthedon
      pictipes (Grote and Robinson) (Lepidoptera: Sesiidae), showed that wounded peach,
      Prunus persica (L.) Batsch, bark was attractive to females for oviposition.
      Females responded to bark that was injured mechanically (e.g., hammer blows,
      knife cuts, pruning wounds), infested by lesser peachtree borer larvae or injured
      by disease. In fact, there was no difference in female oviposition response to
      knife cut wounds and knife cut wounds infested with lesser peachtree borer
      larvae. Oviposition on wounded bark from three different high chill peach
      cultivars was similar and strongly suggests that the narrow genetic base of high
      chill peach cultivars grown in the southeastern United States has little inherent
      resistance to the lesser peachtree borer. In stark contrast, when provided
      different Prunus spp., i.e., exotic peach and the native species P. angustifolia
      and P. serotina, the exotic peach was highly preferred for oviposition by the
      native lesser peachtree borer.

PMID- 19161695
TI  - Effects of operational and environmental factors on evolution of resistance to
      pyriproxyfen in the sweetpotato whitefly (Hemiptera: Aleyrodidae).
AB  - Pyriproxyfen has been an important insecticide used as part of an integrated pest
      management (IPM) program for the sweetpotato whitefly, Bemisia tabaci (Gennadius)
      (B biotype), in Arizona cotton. We used a simulation model to examine the effects
      of pyriproxyfen concentration, insecticide action thresholds, crop diversity,
      planting date, and pyriproxyfen decay on evolution of resistance to pyriproxyfen
      in B. tabaci. In the model, pyriproxyfen use was restricted to cotton with a
      limit of one application per season. Other model parameters were based on data
      from laboratory and field experiments. Whitefly population densities and the
      number of insecticide applications per year increased as resistance evolved.
      Resistance evolved slowest with a low pyriproxyfen concentration. Lower action
      thresholds for pyriproxyfen and higher action thresholds for insecticides other
      than pyriproxyfen also slowed the evolution of resistance. However, lower action
      thresholds for pyriproxyfen resulted in more insecticide sprays per year with a
      high pyriproxyfen concentration. Resistance to pyriproxyfen evolved fastest in
      cotton-intensive regions and slowest in multicrop regions. In regions with
      noncotton crops, increasing immigration to cotton slowed resistance. Resistance
      evolved faster with earlier planting dates, although fewer insecticide sprays
      were needed compared with fields planted later in the year. Faster rates of
      pyriproxyfen decay slowed resistance. In some cases, strategies that delayed
      resistance were effective from an IPM perspective. However, some strategies that
      delayed resistance resulted in higher population densities. Results suggest that
      modification of operational and environmental factors, which can be controlled by
      growers, could prolong the efficacy of pyriproxyfen.

PMID- 19161696
TI  - Black soldier fly (Diptera: Stratiomyidae) larvae reduce Escherichia coli in
      dairy manure.
AB  - Escherichia coli labeled with a green fluorescent protein was inoculated into
      sterile dairy manure at 7.0 log cfu/g. Approximately 125 black soldier fly larvae
      were placed in manure inoculated and homogenized with E. coli. Manure inoculated
      with E. coli but without black soldier fly larvae served as the control. For the
      first experiment, larvae were introduced into 50, 75, 100, or 125 g sterilized
      dairy manure inoculated and homogenized with E. coli and stored 72 h at 27
      degrees C. Black soldier fly larvae significantly reduced E. coli counts in all
      treatments. However, varying the amount of manure provided the black soldier fly
      larvae significantly affected their weight gain and their ability to reduce E.
      coli populations present. For the second experiment, larvae were introduced into
      50 g manure inoculated with E. coli and stored for 72 h at 23, 27, 31, or 35
      degrees C. Minimal bacterial growth was recorded in the control held at 35
      degrees C and was excluded from the analysis. Black soldier fly larvae
      significantly reduced E. coli counts in manure held at remaining temperatures.
      Accordingly, temperature significantly influenced the ability of black soldier
      fly larvae to develop and reduce E. coli counts with greatest suppression
      occurring at 27 degrees C.

PMID- 19161697
TI  - Effects of rootstock and flushing on the incidence of three insects on
      'Clementine de Nules' citrus trees.
AB  - We evaluated the influence of six different citrus rootstocks on the incidence of
      the citrus leafminer, Phyllocnistis citrella Stainton (Lepidoptera:
      Gracillariidae), and the aphid species, Aphis gossypii Glover and A. spiraecola
      Patch (Hemiptera: Aphididae), on 'Clementine de Nules' trees (Citrus clementina
      Hort. ex Tan.). Sampling was conducted during 2005 and 2006 in a grove of 3-yr
      old trees in southern Spain with six rootstocks arranged in a completely
      randomized block design. Incidence (i.e., degree of infestation) and availability
      of resources for herbivores were assessed bi-weekly, and in addition, a "flushing
      index" was estimated as the number of young shoots (as a percentage of total
      shoots) susceptible to herbivore injury. Our results showed that contrasting
      factors affected the incidence of populations of P. citrella, A. gossypii, and A.
      spiraecola on 'Clementine de Nules'. Incidence of P. citrella was significantly
      dependent on the flushing pattern observed throughout the study, whereas the
      reverse was true for the aphid species. Among these, A. spiraecola had similar
      levels of incidence regardless of rootstock, whereas A. gossypii were found
      almost exclusively on leaves of 'Clementine de Nules' grafted on 'Cleopatra
      mandarin' (Citrus reshni Hort. ex Tan). Potential implications of these results
      on pest control are discussed.

PMID- 19161698
TI  - Plant host effect on the development of Heliothis virescens F. (Lepidoptera:
      Noctuidae).
AB  - Heliothis virescens F. is an important polyphagous pest that can develop on >100
      plant species, including 20 economic crops. Populations of this insect are
      believed to be locally maintained on a few crops and weed hosts in Washington
      County, MS. To find the intrinsic value of these plants for the development of H.
      virescens populations, we fed different laboratory and wild colonies with fresh
      and lyophilized plant tissue under a constant temperature. Development time of
      this insect under laboratory conditions varied up to 10 d between plant hosts and
      was dependent on the type of plant tissue provided: fresh or lyophilized. Life
      table parameters such as net reproductive rate, finite rate of increase, and
      generation time indicated that Trifolium repens, a wild host growing around
      agricultural fields year round, could be one of the most suitable local plant
      hosts for the development of H. virescens. Two species of Geranium, previously
      reported as the source of the first H. virescens generation in the region, had
      lower intrinsic value as a food source than did T. repens. Gossyipium hirsutum,
      perhaps the most important crop source of H. virescens in the region, produced
      low net reproductive rate and finite rate of increase parameters. Sampling
      conducted in agricultural fields during 2006 and 2007 found no larvae on the
      above mentioned wild hosts as it was previously reported. Results indicated that
      H. virescens populations in this region were not supported by the wild plant
      species growing around agricultural fields during the time when the survey took
      place.

PMID- 19161699
TI  - Quantitative resistance traits and suitability of woody plant species for a
      polyphagous scarab, Popillia japonica Newman.
AB  - The Japanese beetle, Popillia japonica Newman, has an unusually broad host range
      among deciduous woody plants, yet it feeds only sparingly, or not at all, on
      certain species in the field. We evaluated beetles' preference, survival over
      time and fecundity on eight woody plant species historically rated as susceptible
      or resistant and, after verifying those ratings, tested whether resistance is
      correlated with so-called quantitative defense traits including leaf toughness,
      low nutrient content (water, nitrogen, and sugars), and relatively high amounts
      of tannins or saponins, traditionally associated with such plants. We further
      tested whether species unsuitable for Japanese beetles are also rejected by fall
      webworms, Hyphantria cunea (Drury) (Lepidoptera: Arctiidae), the expected outcome
      if the aforementioned traits serve as broad-based defenses against generalists.
      Choice tests supported historical resistance ratings for the selected species:
      tuliptree, lilac, dogwood, and Bradford callery pear were rejected by Japanese
      beetles, whereas sassafras, cherry plum, Virginia creeper, and littleleaf linden
      were readily eaten. Rejected species also were unsuitable for survival over time,
      or egg-laying, indicating beetles' inability to overcome the resistance factors
      through habituation, compensatory feeding, or detoxification. None of the
      aforementioned leaf traits was consistently higher or lower in the resistant or
      susceptible plants, and plant species rejected by Japanese beetles often were not
      rejected by fall webworms. Specialized secondary chemistry, not quantitative
      defenses, likely determines the Japanese beetle's dietary range among deciduous
      woody plant species it may encounter.

PMID- 19161700
TI  - Maize phenology affects establishment, damage, and development of the western
      corn rootworm (Coleoptera: Chrysomelidae).
AB  - The effects of maize (Zea mays L.) phenology on establishment and adult emergence
      of the western corn rootworm (Diabrotica virgifera virgifera LeConte) and plant
      damage to maize was evaluated in field trials in 2001 and 2002 and in the
      greenhouse. Although neonate western corn rootworm larvae were able to initially
      establish on maize roots during anthesis and early reproductive stages, these
      older roots were apparently unsuitable for complete western corn rootworm larval
      development. The number of western corn rootworm beetles that emerged from eggs
      that hatched during anthesis to early reproductive stages was significantly fewer
      than the number of beetles that eclosed from V4 to V11. Plant damage was also
      lowest from larvae that eclosed during anthesis to early reproductive stages.
      Potential causal mechanisms and implications of these data in terms of potential
      management strategies in the future are discussed.

PMID- 19161701
TI  - Effect of host plants on successful parasitism by Haeckeliania sperata
      (Hymenoptera: Trichogrammatidae) on Diaprepes abbreviatus (Coleoptera:
      Curculionidae) eggs.
AB  - Diaprepes abbreviatus L. is a highly polyphagous root weevil that causes damage
      to several fruit crops, ornamental plants, and other naturally occurring plants
      in Florida. Haeckeliania sperata Pinto is a gregarious endoparasitoid that
      attacks D. abbreviatus eggs. We hypothesized that the reproductive success of H.
      sperata is affected by the host plant of D. abbreviatus. Six host plants with
      varying degrees of pubescence were used to determine the effect of leaf trichomes
      on the searching behavior and success of parasitism by H. sperata. No-choice
      tests showed that H. sperata was able to parasitize Diaprepes eggs laid on the
      six host plants. However, the plants with a high trichome density on their leaves
      had a lower percent of parasitism than the plants with smoother leaves. Removing
      trichomes from a host plant showed that the presence of some leaf trichomes had a
      negative effect on the overall searching efficiency of H. sperata. The presence
      of trichomes decreased the total distance traveled and increased the total search
      time of H. sperata females, resulting in a lower searching speed. Multiple
      regression analysis was used to establish the relationship between percent
      parasitism and leaf trichome density, leaf thickness, and the searching speed of
      H. sperata. Searching speed was the best predictor of percent parasitism; this
      parameter could be used to predict the suitability of host plants for the
      establishment of H. sperata. Our findings suggest that the reproductive success
      of H. sperata is affected by the host plant of D. abbreviatus.

PMID- 19161702
TI  - Do plant viruses facilitate their aphid vectors by inducing symptoms that alter
      behavior and performance?
AB  - Aphids can respond both positively and negatively to virus-induced modifications
      of the shared host plant. It can be speculated that viruses dependent on aphids
      for their transmission might evolve to induce changes in the host plant that
      attract aphids and improve their performance, subsequently enhancing the success
      of the pathogen itself. We studied how pea aphids [Acyrthosiphon pisum (Harris)]
      responded to infection of tic beans (Vicia faba L.) by three viruses with varying
      degrees of dependence on this aphid for their transmission: pea enation mosaic
      virus (PEMV), bean yellow mosaic virus (BYMV), and broad bean mottle virus
      (BBMV). BYMV has a nonpersistent mode of transmission by aphids, whereas PEMV is
      transmitted in a circulative-persistent manner. BBMV is not aphid transmitted.
      When reared on plants infected by PEMV, no changes in aphid survival, growth, or
      reproductive performance were observed, whereas infection of beans by the other
      aphid-dependent virus, BYMV, actually caused a reduction in aphid survival in
      some assays. None of the viruses induced A. pisum to increase production of
      winged progeny, and aphids settled preferentially on leaf tissue from plants
      infected by all three viruses, the likely mechanism being visual responses to
      yellowing of foliage. Thus, in this system, the attractiveness of an infected
      host plant and its quality in terms of aphid growth and reproduction were not
      related to the pathogen's dependence on the aphid for transmission to new hosts.

PMID- 19161703
TI  - Density and composition of an insect population in a field trial of chitinase
      transgenic and wild-type silver birch (Betula pendula) clones.
AB  - Fifteen silver birch (Betula pendula Roth) lines carrying a sugar beet chitinase
      IV gene and eight wild-type birch clones were grown in a field trial. The
      composition and density of the insect population and the leaf damage caused by
      insects were monitored and compared between transgenic and wild-type trees. The
      most abundant insect group in all trees was aphids, and the variation in total
      insect densities was mainly explained by the variation in aphid densities. Insect
      densities were generally higher in the transgenic than in the control trees,
      indicating that the expression of the sugar beet chitinase IV gene had an
      influence on the suitability of birch leaves to aphids. The level of leaf damage
      was higher among transgenic than among control trees. Chewing damage was the most
      common type of leaf damage in all trees. The number of different damage types was
      higher among the wild-type clones than among the transgenic lines or their
      controls. The results indicate that the chitinase transgenic trees are more
      susceptible to aphids and suffer higher levels of leaf damage than the control
      trees. In the composition of the damage types, the control trees were more
      similar to the transgenic than to other wild-type trees, indicating that the
      composition was mostly linked to the genotype of the tree and not to the
      expression of the transgene. This study provides important information on the
      ecological interactions of chitinase transgenic trees in the field trial. No
      clear harmful effects of transgenic chitinase on the biodiversity of insect
      population were detected.

PMID- 19161704
TI  - [University education of health professionals: "Core Values" as a valid
      instrument for evaluating performance values in future practice].
AB  - In the caring professions it is important to be able to assess not only knowledge
      and competencies but also the behavior of future professionals in the different
      sectors of health care. The aim of this work is to define and describe the core
      values of the health professions and shed light on the essential values which act
      as the basis for future behavior. Many international documents (League of
      Nursing, American Board of International Medicine), define the Core Values of
      specific professions as the bases on which teaching and training curricula are
      founded. The authors intend to find out whether it is possible to improve
      behavioral learning of professional values. For example, in the USA the Medical
      Association has proposed a model for this purpose. Before receiving professional
      abilitation, suitable professional behavior should be practically tested.
      MATERIALS AND METHODS: A questionnaire was issued to University course
      Coordinators in Nursing and Obstetrics in Italy, asking them to express their
      opinion on an existing model of "Core Values" and the need for their assessment.
      RESULTS: It was generally agreed that behavior should be assessed in the light of
      the essential values of the profession. The description of "Core Values" thus
      becomes a tool for identifying which behavior should be assessed. Coordinators
      did not express a precise opinion regarding the assessment tool proposed.
      DISCUSSION AND CONCLUSIONS: There was a general consensus regarding the need to
      assess the values at the basis of behavior in health care students, as well as
      the "Core Value" proposed. Doubt remained regarding the assessment modalities
      owing to the fact that the practical test actually used does not always focus on
      behavioral values.

PMID- 19161705
TI  - [Problem solving abilities of nursing students: the experience of the bachelor
      degree course in nursing at the University of Udine].
AB  - The process nurses adopt to solve the patients' problems is known as "Problem
      Solving" in the literature. Problem Solving Abilities include Diagnostic
      Reasoning, Prognostic Judgment and Decision Making. Nursing students apply the
      Problem Solving to the Nursing Process that is the mental and operative approach
      that nurses use to plan the nursing care. The purpose of the present study is to
      examine if there is a positive relationship between the number of Educational
      Tutorial Strategies (Briefing, Debriefing and Discussion according to the
      Objective Structured Clinical Examination Methodology) used for nursing students
      and their learning of Problem Solving Abilities (Diagnostic Reasoning, Prognostic
      Judgment and Decision Making). The study design was retrospective, descriptive
      and comparative. The Problem Solving Instrument, specifically developed for this
      study and proved for its reliability and validity, was used to collect the data
      from a sample of 106 nursing care plans elaborated by the second-year students of
      the Bachelor Degree in Nursing of the University of Udine. Nursing care plans
      were elaborated during three times consecutively, after students had participated
      in different Educational Tutorial Strategies. Results showed that the more the
      students took part in a higher number of Educational Tutorial Strategies the more
      they significantly increased their Problem Solving Abilities. The results
      demonstrate that it is important to use Educational Tutorial Strategies in the
      nursing education to teach skills.

PMID- 19161706
TI  - [Mentor and neophyte relationship: a phenomenological study about novice nurses'
      socialization in intensive care unit].
AB  - GOAL: this article is aimed at examining the relationship and experience between
      expert and novice nurses in intensive care unit; it also assesses the
      implementation of mentorship functions by expert nurses. DESIGN:
      phenomenological. SETTING: three university hospitals, in Milan. SAMPLE: 11
      expert nurses, 11 novice nurses. OUTCOME MEASUREMENT: the expert and novice
      nurses of our sample have been interviewed in a semi-structured context; the
      interviews have been audio taped and transcribed. The results of transcription
      have been analyzed through the Van Kaam method, to find major topics, and
      compared the topics found with the literature reviewed. Furthermore Darling's
      questionnaire was tested, as a pilot study, to assess the implementation of
      mentorship functions by expert nurses. RESULTS: during the first three months in
      ICU, novice nurses experienced a reality shock. They said that the environment
      was very different from the other wards, patients were complex and unstable and
      there were too many things to learn. Frequently they felt frustration and
      inadequacy. For novice nurses positive mentoring experience, group support,
      congruent assignment and evaluation were related to high self-confidence, low
      anxiety, high job satisfaction, and low intention to leave the unit. Despite
      there were not formal mentoring program in the structure analyzed, novice nurses
      gave high evaluation to expert nurses in Darling's questionnaire. CONCLUSION: the
      socialization process of a neophyte in ICU is complex. Therefore, it is necessary
      to plan it very well. Great importance have in this period mentor relationship,
      group support, congruent assignment and evaluation. This things could lower
      voluntary turnover and shortage, two big problems for the nowadays nursing
      profession. It could be interesting to implement a formal mentoring program in
      Italy too, to assess the practicability of it.

PMID- 19161707
TI  - [Pain and basic functional activites in a group of patients with cutaneous wounds
      under V.A.C therapy in hospital setting].
AB  - INTRODUCTION: Topical Negative Pressure Wound Therapy (NPWT), in Italy known as
      V.A.C. (Vacuum Assisted Closure) system, is used for the management of chronic
      wounds not responding to conventional therapies. To date, no data concerning the
      impact of this device on pain, functional activities and pain-killers'
      administration , is available. MATERIALS AND METHODS: over a 3-year period, 32
      patients with cutaneous wounds undergoing V.A.C. therapy were admitted. Data
      related to 25 patients with an average age of 62.7 years was collected. Pain,
      patient autonomy and consumption of analgesic drugs were evaluated before and
      during V.A.C. therapy. RESULTS: The average pain score without V.A.C. was 4.2 +/-
      2.4) during the first day of therapy the average pain score was 6.2 +/- 2.8).
      Before and after V.A.C. therapy, a similar number of patients (17/25 vs 19/25)
      used pain-killers, but the dosage had to be noticeably increased; 5 patients out
      of 25 asked for the interruption of V.A.C. therapy due to pain. The therapeutic
      response to the pain-killers was poor. Among 25 patients, the number of the basic
      functions lost before V.A.C. therapy was 20 , but under V.A.C. therapy another 49
      functions were lost, bringing the total to 69. DISCUSSION: Cutaneous wounds often
      represent a painful experience for the patients. Despite the strong increase in
      the consumption of pain-killers, there was an increased level of pain and a
      higher degree of dependence during the V.A.C. therapy. Healthcare professionals
      tended to underestimate the impact of the device in the genesis of the pain
      reported by patients. CONCLUSIONS: When selecting the type of treatment, the pain
      of the patient should be considered as a primary outcome. Increased levels of
      pain associated with the loss of autonomy during V.A.C. therapy increase nurses'
      workload and worsen patients' quality of life. However, these factors are not
      considered in the cost-benefit analyses.

PMID- 19161710
TI  - An outbreak of non-typeable MRSA within a residential care facility.
AB  - In a household setting within a residential care facility for visually and
      intellectually disabled people, a resident (index case) was diagnosed with dermal
      abscesses caused by a methicillin-resistant Staphylococcus aureus (MRSA) which
      was non-typeable by standard pulsed-field gel electrophoresis. All residents and
      staff in contact with the index case (a total of 200 people) were screened for
      MRSA.

PMID- 19161711
TI  - A measles outbreak in Croatia, 2008.
AB  - We report an outbreak of measles in Croatia, involving 49 cases with onset of
      symptoms between end of April and June 2008. Cases occurred in Zagreb and
      Slavonski Brod but investigations indicated a common epidemiological link between
      these two geographically separate regions.

PMID- 19161712
TI  - Imported aseptic meningitis due to Toscana virus acquired on the island of Elba,
      Italy, August 2008.
AB  - We describe a case of aseptic meningitis due to Toscana Virus imported to
      Switzerland and discuss the epidemiological situation. To our knowledge this is
      the first description of this infection acquired on the Island of Elba.

PMID- 19161713
TI  - Botulism in injecting drug users, Dublin, Ireland, November-December 2008.
AB  - In November and December 2008, six cases of suspect wound botulism were reported
      in heroin injecting drug users, all residents in Dublin, Ireland. Patients were
      aged between 23-42 years of age; four cases were male; one patient died shortly
      after admission. The patients presented to four different hospitals across the
      city. Botulism in injecting drug users in Ireland was last reported in 2002.

PMID- 19161715
TI  - High rates of community-acquired, Panton-Valentine leukocidin (PVL)- positive
      methicillin-resistant S. aureus (MRSA) infections in adult outpatients in Greece.
AB  - Staphylococcus aureus was isolated in 88 (30.8%) of 286 adult patients suffering
      from various skin and soft-tissue infections examined in the outpatient
      department of a 650 bed tertiary-care hospital of Athens, Greece between January
      2006 and December 2007. Twenty-seven (30.7%) of the S. aureus infections were
      caused by methicillin-resistant S. aureus (MRSA). All MRSA isolates were also
      resistant to tetracycline, fucidic acid and kanamycin, but were sensitive to
      gentamicin and tobramycin, as well as to to cotrimoxazole, chloramphenicol,
      quinolones, clindamycin and erythromycin. All isolates belonged to staphylococcal
      cassette chromosome mec elements (SCCmec) type IV, and were found to carry the
      lukF-PV and lukS genes coding for Panton-Valentine leukocidin (PVL). Pulsed-field
      gel electrophoresis (PFGE) and spa-typing revealed high genetic similarity among
      all MRSA isolates and with the PFGE pattern of the well-described ST80 clone that
      seems to be spreading through Europe. The high prevalence of MRSA among S. aureus
      infections in the community signify that empiric therapy in Greece, when
      clinically indicated, should exclude beta-lactam antibiotics. Moreover, the
      establishment of an active screening for PVL-positive community-acquired (CA)
      MRSA carriage and the adoption of a search and destroy strategy for CA-MRSA in
      all patients admitted with purulent skin and soft-tissue is of high priority in
      Greece as well as in all European countries which face high rates of CA-MRSA
      infection.

PMID- 19161716
TI  - An outbreak of measles in orthodox Jewish communities in Antwerp, Belgium, 2007
      2008: different reasons for accumulation of susceptibles.
AB  - From August 2007 to May 2008, an outbreak of at least 137 cases of measles
      occurred in some orthodox Jewish communities in Antwerp, Belgium. The outbreak
      was linked to outbreaks in the same communities in the United Kingdom and in
      Israel. The reasons for this outbreak were diverse: cultural factors,
      misinformation on vaccination by some medical doctors and the lack of a catch-up
      vaccination programme in private Jewish schools. The identification of smaller
      susceptible groups for measles transmission and vaccination of these groups
      represent a major challenge for the measles elimination programme.

PMID- 19161717
TI  - Long-term Cryptosporidium typing reveals the aetiology and species-specific
      epidemiology of human cryptosporidiosis in England and Wales, 2000 to 2003.
AB  - To improve understanding of the aetiology and epidemiology of human
      cryptosporidiosis, over 8,000 Cryptosporidium isolates were submitted for typing
      to the species level over a four year period. The majority were either
      Cryptosporidium parvum (45.9%) or Cryptosporidium hominis (49.2%). Dual infection
      occurred in 40 (0.5%) cases and six other known Cryptosporidium species or
      genotypes were found in 67 (0.9%) cases. These were Cryptosporidium meleagridis,
      Cryptosporidium felis, Cryptosporidium canis, and the Cryptosporidium cervine,
      horse and skunk genotypes. The remaining 3.5% were not typable. Epidemiology
      differed between infecting species. C. parvum cases were younger, although C.
      hominis was more prevalent in infants under one year and in females aged 15 to 44
      years. Spring peaks in cases reported to national surveillance were due to C.
      parvum, while C. hominis was more prevalent during the late summer and early
      autumn as well as in patients reporting recent foreign travel. Temporal and
      geographical differences were observed and a decline in C. parvum cases persisted
      from 2001. Typing of isolates allowed outbreaks to be more clearly delineated,
      and demonstrated anthroponotic spread of C. parvum as well as C. hominis. Our
      findings suggest that national surveillance for Cryptosporidium should be
      conducted at the species level.

PMID- 19161718
TI  - Rebound of overdose mortality in the European Union 2003-2005: findings from the
      2008 EMCDDA Annual Report.
AB  - Drug overdose is an important cause of death among young adults in Europe.
      According to data reported by Member States to the EMCDDA, many of the European
      Union countries reported a rebound in the numbers of overdose deaths in 2003
      2005, following decreases in almost all reporting countries in previous years
      (2000 to 2003). Further investigations are needed in order to clarify the factor
      driving these increases and inform policies and interventions aimed at reducing
      these deaths.

PMID- 19161719
TI  - Legionnaires disease in a neonatal unit of a private hospital, Cyprus, December
      2008: preliminary outbreak report.
AB  - We report an outbreak of Legionnaires disease in neonates, affecting 11 newborn
      babies. The case fatality rate is currently 27%. The outbreak has been confirmed
      by detection of Legionella pneumophila antigen in eight of the 11 cases. Tests
      are in progress to determine the source of infection.

PMID- 19161722
TI  - Start of the influenza season 2008-9 in Europe - increasing influenza activity
      moving from West to East dominated by A(H3N2).
AB  - The influenza season 2008-9 started in week 49 of 2008 and is so far
      characterised by influenza virus type A subtype H3N2. Isolates of this subtype
      that were tested proved susceptible to neuraminidase inhibitors, but resistant to
      M2 inhibitors. The circulating A(H3N2) viruses are antigenically similar to the
      component in the current northern hemisphere influenza vaccine.

PMID- 19161723
TI  - Zoonotic infections in Europe in 2007: a summary of the EFSA-ECDC annual report.
AB  - The European Food Safety Authority and the European Centre for Disease Prevention
      and Control have just published their Community Zoonoses Report for 2007,
      analysing the occurrence of infectious diseases transmittable from animals to
      humans. Campylobacter infections still topped the list of zoonotic diseases in
      the European Union and the number of Salmonella infections in humans decreased
      for the fourth year in a row. Cases of listeriosis remained at the same level as
      in 2006, but due to the severity of the disease, more studies on transmission
      routes are warranted. The report highlights the importance of continued co
      operation between veterinarians and public health specialists, both at the EU
      level and within Member States.

PMID- 19161724
TI  - Cluster of hepatitis A cases among travellers returning from Egypt, Germany,
      September through November 2008.
AB  - From September to November 2008, 34 cases of hepatitis A imported from Egypt were
      reported to the German public health authorities. Investigations point to a
      continuing common source of infection, most likely linked to Nile river cruises.
      The patients affected had not been vaccinated, which emphasises the need for more
      effective travel advice before trips to hepatitis A endemic countries.

PMID- 19161725
TI  - Cluster of hepatitis A cases among travellers returning from Egypt, Belgium,
      September through November 2008.
AB  - Following a European alert by France, we detected a hepatitis A cluster in
      Belgian travellers returning from Egypt. Our investigation supports the
      hypothesis of a common source outbreak, linked to Nile river cruises. The
      outbreak also suggests the need to consider an intensification of the vaccination
      policy for travellers to hepatitis A endemic countries.

PMID- 19161726
TI  - Cluster of cases of hepatitis A with a travel history to Egypt, September
      November 2008, France.
AB  - Since September 2008, 26 cases of hepatitis A with a history of travel to Egypt
      have been reported in France. Investigations indicate that a common source of
      contamination linked to Nile river cruises is the most likely explanation of the
      increase in the number of cases reported in France as well as in several other
      European Union countries.

PMID- 19161727
TI  - Hepatitis A outbreak in a Roma village in eastern Slovakia, August-November 2008.
AB  - We describe an outbreak of hepatitis A in Lomnicka, a village in the eastern part
      of Slovakia. The outbreak was limited to the village and did not spread either to
      other districts of Slovakia or to the neighbouring countries. The number of cases
      reported from 28 August to 30 November 2008 was 298. All cases but one occurred
      in the Roma population. The outbreak was associated with low socio-economic
      conditions which facilitated person-to-person transmission. No common source of
      the outbreak was verified.

PMID- 19161728
TI  - Community-wide outbreak of hepatitis A in Latvia in 2008 - an update.
AB  - An outbreak of hepatitis A has been ongoing in Latvia with 2,817 confirmed cases
      reported between 20 November 2007 and 31 December 2008. Initially the spread of
      infection was due to transmission among drug users and other high-risk groups, as
      well as several outbreaks in Riga (affecting a school and a restaurant), but in
      the second half of the year led to a community-wide increase in the number of
      cases. Molecular analysis of 100 strains showed that 95 belonged to genotype IA,
      of which 89 were identical and six were single nucleotide variants of the same
      sequence.

PMID- 19161729
TI  - Increase in hepatitis A cases in the Czech Republic in 2008 - an update.
AB  - In 2008, 1,616 cases of hepatitis A were reported in the Czech Republic, more
      than a 10-fold increase compared with the annual number of cases registered in
      2003-2007. The infection was initially associated with injecting drug users, most
      probably by person-to-person contact or parenteral transmission, and in the
      second half of the year continued to spread among the general population with
      increased susceptibility.

PMID- 19161730
TI  - Hepatitis A in the European Union: responding to challenges related to new
      epidemiological patterns.

PMID- 19161731
TI  - Tumor thrombus in right atrium from lung adenocarcinoma.
AB  - We report a case referred for elective surgery to remove an intra-atrial
      extension of a tumor thrombus. The patient underwent surgical excision of the
      mass because he would have a high risk of sudden death, pulmonary embolism, or
      tricuspid obstruction. A histologic examination established the diagnosis of lung
      adenocarcinoma metastases.

PMID- 19161732
TI  - A new hemostatic agent: initial life-saving experience with Celox (chitosan) in
      cardiothoracic surgery.
AB  - Celox (MedTrade Products Ltd, Cheshire, UK) is a proprietary preparation of
      chitosan, indicated for moderate to severe hemorrhage and currently used for
      hemostasis in the emergency and military settings. We describe its lifesaving use
      in 2 patients undergoing cardiothoracic surgery in which conventional techniques
      had failed.

PMID- 19161733
TI  - Immediate myocardial infarction due to compression of a vein graft.

PMID- 19161734
TI  - A dangerous venous variation in thoracoscopic right lower lobectomy.
AB  - Anatomical variations of the pulmonary vessels present a potential risk of
      intraoperative bleeding and damage to pulmonary circulation during pulmonary
      resection. We present details of a dangerous variation of the superior pulmonary
      vein associated with thoracoscopic right lower lobectomy that could potentially
      be divided if there was no preoperative foreknowledge of individual vessel
      configurations.

PMID- 19161735
TI  - Guidelines for reporting mortality and morbidity after cardiac valve
      interventions--need for a reappraisal?

PMID- 19161738
TI  - Cumulative sum curves and their prediction limits.

PMID- 19161739
TI  - Clinical significance of tumor-infiltrating lymphocytes in lung neoplasms.
AB  - BACKGROUND: Tumor-infiltrating lymphocytes (TIL) are considered important in
      anticancer immunosurveillance, although their role has not been clearly
      established yet. We examined prevalence, correlations, and prognostic
      significance of TIL among our patient population of resected lung neoplasms.
      METHODS: From 1993 to 2006, the presence of TIL was retrospectively evaluated in
      1,290 patients operated on for primary lung neoplasms. Tumor-infiltrating
      lymphocytes were defined as those intraepithelial lymphocytes located within the
      cancer cell nests. RESULTS: Tumor-infiltrating lymphocytes were detected in 294
      patients (23%). A significant difference was found between prevalence in non
      small cell lung carcinomas versus neuroendocrine tumors (290 of 1,208, 24% versus
      4 of 82, 5%; p = 0.0001). Prevalence was similar in adenocarcinomas, squamous
      cell carcinomas, and large-cell anaplastic carcinomas. Logistic regression
      analysis indicates that TIL correlate with grading (odds ratio, 1.27; 95%
      confidence interval, 1.04 to 1.55; p = 0.02), tumor dimension (odds ratio, 0.86;
      95% confidence interval, 0.79 to 0.94; p = 0.0008), and vascular invasion (odds
      ratio, 1.62; 95% confidence interval, 1.21 to 2.16; p = 0.0009). A not
      significantly better survival in the presence of TIL was observed overall (p =
      0.20), becoming significant in squamous-cell carcinomas (p = 0.03). In patients
      with stage I disease, TIL is associated with a significant survival advantage in
      squamous-cell carcinomas (p = 0.03). The survival advantage increases with the
      duration of follow-up and is more evident after 4 to 6 years. CONCLUSIONS: Tumor
      infiltrating lymphocytes are observed in about one fourth of resected lung
      neoplasms: they are rare in neuroendocrine tumors. Tumor-infiltrating lymphocytes
      are more frequent in poorly differentiated tumors and in tumors with microscopic
      vascular invasion. The presence of TIL correlates with an improved survival in
      squamous cell carcinomas, particularly at early stage. The survival advantage
      increases with the duration of follow-up.

PMID- 19161740
TI  - Transbronchial needle aspiration in lung cancer patients suitable for operation
      with positive mediastinal positron emission tomography.
AB  - BACKGROUND: The objectives of this study were to analyze our experience with
      transbronchial needle aspiration as a minimally invasive procedure alternative to
      mediastinoscopy in the preoperative staging of non-small cell lung cancer
      patients with positive mediastinal positron emission tomography and to propose a
      staging algorithm that combines performance characteristics of these three
      methods. METHODS: Fifty-one patients staged N2 or N3 after positron emission
      tomography imaging underwent transbronchial needle aspiration. RESULTS: A
      malignant adenopathy was identified in 26 patients (51%) that were excluded from
      operation and referred for neoadjuvant chemotherapy or chemoradiotherapy
      according to the mediastinal status (N2 or N3), as determined on the positron
      emission tomography image. In the remaining 25 patients (49%), samples were
      considered adequate negative in 12 patients, inadequate in 11, or inconclusive in
      2. These patients underwent mediastinoscopy. Mediastinoscopy showed N2 disease in
      19 cases, and the patients received neoadjuvant chemotherapy. In the remaining 6
      cases no mediastinal involvement was identified and patients underwent operation.
      Postoperatively, 5 patients were staged N0 and 1 was staged N2. For
      transbronchial needle aspiration, sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy were 76%, 100%, 100%, 33%, and
      79%, respectively. CONCLUSIONS: Transbronchial needle aspiration avoided a
      mediastinoscopy in approximately half of lung cancer patients referred for
      operation with positive mediastinal positron emission tomography, sparing the
      associated costs and risks of more invasive surgical procedures. The minimally
      invasive mediastinal staging algorithm that we proposed seems to be efficacious
      and easily applicable in clinical practice.

PMID- 19161741
TI  - Invited commentary.

PMID- 19161742
TI  - Intraoperative radiofrequency ablation of lung metastases and histologic
      evaluation.
AB  - BACKGROUND: Radiofrequency ablation (RFA) has received high interest in the
      treatment of primary and secondary lung neoplasms. Clinical experience continues
      to accumulate; however, the biologic effects after ablation remain poorly
      understood. This study evaluated the safety and feasibility of RFA in an open
      thoracotomy setting and investigated the early histopathologic changes after RFA.
      METHODS: The study enrolled 18 subjects with multiple pulmonary metastases from a
      solid primary tumor. RFA was performed at an open thoracotomy setting, followed
      by wedge resection of the ablated tumor. RESULTS: No intraoperative complications
      during the RFA procedure occurred. Immunostaining revealed a complete ablation in
      7 patients (39%). The grade of ablation was greater than 90% in 9 patients (50%),
      and less than 90% in 2 (11%). No correlation was found between the grade of
      ablation and the applied energy and the diameter of the lesion. CONCLUSIONS:
      Intraoperative RFA in an open thoracotomy setting appears to be a safe and
      feasible technique. Tumor devitalization sufficient for local control was
      achieved in 89% in our series. Ablation was incomplete in 11%, subject to the
      methods used in this study. This result appears to be inferior to metastasectomy
      by surgical resection.

PMID- 19161743
TI  - Invited commentary.

PMID- 19161744
TI  - Comparative clinical outcomes of thymectomy for myasthenia gravis performed by
      extended transsternal and minimally invasive approaches.
AB  - BACKGROUND: Both transsternal and video-assisted thoracoscopic surgery (VATS)
      approaches are used for thymectomy in myasthenia gravis. We compared outcomes of
      simultaneous experiences in two institutions: one utilizing the transsternal
      approach exclusively, the other using VATS procedures for all patients. The
      Myasthenia Gravis Foundation of America guidelines were used to standardize
      reporting. METHODS: Between March 1992 and September 2006, 95 thymectomies were
      performed for myasthenia gravis; 48 by VATS and 47 by transsternal approach.
      Preoperative classification and postoperative disease status were compared
      between the groups. RESULTS: Mean age was 39.8 +/- 14.9 (VATS) versus 34.4 +/-
      13.2 years (transsternal) (p = 0.07); the proportion of females was 52% versus
      67% (p = 0.15); and preoperative duration of myasthenia gravis was 27 +/- 44
      versus 20 +/- 45 months (p = 0.43), respectively. Clinical follow up was 89.5%
      complete at a mean of 6.0 +/- 4.0 years and 4.3 +/- 2.9 years (p = 0.03). The
      operative time was 128 +/- 34 minutes (VATS) versus 119 +/- 27 minutes
      (transsternal) (p = 0.22). The need for postoperative ventilation was 4.2% versus
      16.2% (p = 0.07) and mean length of stay was 1.9 +/- 2.6 versus 4.6 +/- 4.2 days
      (p < 0.001). Thymomas were found in 8.3% of VATS versus 13.3% of transsternal
      patients (p = 0.44). No myasthenia gravis related deaths occurred and 95.8% of
      the VATS and 97.9% of the transsternal patients were in either complete stable
      remission, pharmacologic remission, or minimal manifestations status. In the VATS
      group, 13 of 17 (76.5%) patients stopped prednisone usage after surgery versus 5
      of 14 (35.7%) in the transsternal group (p = 0.022). CONCLUSIONS: Thymectomy is
      an effective treatment in patients with myasthenia gravis with equivalent
      clinical outcomes obtained by either approach.

PMID- 19161745
TI  - Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal
      cancer is associated with enhanced survival.
AB  - BACKGROUND: Neoadjuvant chemoradiotherapy followed by esophagogastrectomy has
      become the standard of care for patients with locally advanced esophageal cancer.
      This report analyzes our experience with this treatment approach. METHODS: From
      January 1998 through December 2003, all patients from a single institution
      receiving neoadjuvant chemoradiotherapy followed by esophagogastrectomy were
      reviewed for operative mortality, morbidity, long-term survival, and factors
      affecting survival. Only patients preoperatively staged with both computed
      tomographic scans and endoscopic ultrasound were included. RESULTS: There were
      162 patients (142 men, 20 women), and the median age was 61 years (range, 22 to
      81 years). Histopathology was adenocarcinoma in 143 patients and squamous cell in
      19. Pretreatment clinical stage was II in 28 patients (17%), III in 111 (68%),
      and IV (M1a) in 23 (14%). Ivor Lewis esophagogastrectomy was the most common
      procedure, occurring in 132 patients. Operative mortality and morbidity was 4.9%
      and 37%, respectively. Pathologic response was complete in 42 patients (26%),
      near complete in 27 (17%), partial in 88 (54%), and unresectable in 5 (3%). Five
      year survival for overall, complete, near complete, and partial response patients
      was 34%, 55%, 27%, and 27%, respectively (p = 0.013). Patients whose lymph nodes
      were rendered free of cancer showed improved overall and disease-free survival
      compared with patients having persistently positive lymph nodes (p = 0.019).
      CONCLUSIONS: Esophagogastrectomy after neoadjuvant chemoradiotherapy can be
      performed with low mortality and morbidity. Patients with complete pathologic
      response have significantly improved long-term survival compared with patients
      with near complete and partial responses. Future efforts should be directed at
      understanding determinants of complete responses.

PMID- 19161746
TI  - Anterior versus posterior routes of reconstruction after esophagectomy: a
      comparative anatomic study.
AB  - BACKGROUND: A gastric conduit is commonly used to reconstruct the alimentary
      tract after esophagectomy for esophageal cancer. The choice of anterior versus
      posterior route for reconstruction is debatable, and longer distance of the
      reconstructed routes may be associated with higher tension exerted on the
      transposed stomach. The aim of this study is to evaluate the length of both the
      anterior and posterior routes in a group of patients measured intraoperatively
      during esophagectomy for esophageal cancer. METHODS: Sixty consecutive and
      nonselected patients with thoracic esophageal cancer were accrued in this
      prospective study. Measurements of the anterior (retrosternal) and posterior
      routes were performed after esophagectomy but before reconstruction with gastric
      conduit, from the cricoid cartilage to the pyloric ring. RESULTS: The lengths of
      the anterior and posterior routes were 32.68 +/- 2.67 cm and 35.48 +/- 2.93 cm,
      respectively (p < 0.001). The anterior route is significantly shorter than the
      posterior route. CONCLUSIONS: The anterior (retrosternal) route is the shorter
      passage for the reconstruction of the alimentary tract using the stomach after
      esophagectomy.

PMID- 19161747
TI  - Radiofrequency ablation of Barrett's esophagus: short-term results.
AB  - BACKGROUND: The presence of Barrett's esophagus (BE) increases the risk of
      esophageal cancer. Total regression of BE is uncommon with medication or
      laparoscopic fundoplication, and endoscopic techniques to obliterate BE have
      varied results. This study evaluated the early results of a balloon-based
      catheter radiofrequency ablation (RFA) system in patients with medically
      refractory reflux symptoms and biopsy-proven BE. METHODS: The medical records of
      27 consecutive patients who underwent RFA for BE from March 2005 through January
      2007 were reviewed. Esophagogastroduodenoscopy was performed before ablation to
      document presence of BE and no cancer and at 8 weeks after the RFA to assess the
      presence of residual BE. RESULTS: Mean patient age was 53.6 +/- 12.5 years; 16
      (59%) were men. The average length of the Barrett segment treated was 4.6 +/- 4.7
      cm. Two patients (7.4%) had low-grade dysplasia. No patient had high-grade
      dysplasia and cancer. There was no periprocedural morbidity or at follow-up, no
      postprocedure dysphagia or stricture. In all patients, the BE was completely
      replaced with normal squamous epithelium. Symptoms regressed in 16 patients (60%)
      with RFA and proton pump inhibitor therapy. Eleven required an antireflux
      procedure for persistent symptoms. CONCLUSIONS: Short-term results show that RFA
      for BE is safe and achieves 100% replacement of intestinal metaplasia. RFA of BE
      combined with fundoplication may be offered to patients with BE and medically
      refractory reflux symptoms. Long-term endoscopic surveillance is needed to
      determine if the risk of cancer is reduced with this bimodality therapy.

PMID- 19161748
TI  - Impact of obesity on perioperative outcomes of minimally invasive esophagectomy.
AB  - BACKGROUND: Abnormal body mass index has been targeted as a predictor of
      complications after major surgery. The aim of this study was to review the impact
      of obesity on perioperative outcomes after minimally invasive esophagectomy.
      METHODS: This study was a single-institution retrospective review of patients
      undergoing minimally invasive esophagectomy for high-grade dysplasia or cancer of
      the esophagus between 1999 and 2004. A body mass index of 30 or greater was
      considered obese. Patients with a body mass index less than 18.5 were excluded
      because of the potentially adverse effects of malnutrition on outcomes. RESULTS:
      A total of 282 eligible patients were identified. There were 84 obese and 198
      nonobese patients (mean body mass index = 34.5 versus 25.5; p < 0.0001).
      Preoperative demographics, comorbidities, and cancer status were similar, except
      for a higher prevalence of diabetes (p = 0.002), lower prevalence of peripheral
      vascular disease (p = 0.045), and lower prevalence of stage III disease in the
      obese group (p = 0.044). Operative time was significantly longer in obese
      patients (375 versus 301 minutes; p = 0.0001), and estimated blood loss was
      similar (433 versus 377 mL, obese versus nonobese, respectively). There were 5
      (1.8%) overall 30-day perioperative mortalities, with no differences between the
      groups. Overall major (obese, 23 [27.5%] versus nonobese, 68 [34.3%]) and minor
      (obese, 23 [27.5%] versus nonobese, 65 [32.8%]) complication rates were also
      similar. Furthermore, there were no significant differences in any individual
      complications. There was no difference in median intensive care unit stay (obese,
      1 day versus nonobese, 2 days) or overall hospital stay (obese, 7 days versus
      nonobese, 8 days). CONCLUSIONS: Obesity was associated with longer operative
      times. Our review suggests that obesity is not a risk factor for mortality,
      postoperative complications, or length of hospitalization after minimally
      invasive esophagectomy.

PMID- 19161749
TI  - Protocols for Paget-Schroetter syndrome and late treatment of chronic subclavian
      vein obstruction.
AB  - BACKGROUND: Paget-Schroetter syndrome is a serious condition that if not treated
      promptly and properly leads to severe sequelae and permanent disability. In its
      late stage, chronic fibrous obliteration of the vein is rarely amenable to
      surgical treatment, except in very few select cases. METHODS: We treated 126
      Paget-Schroetter syndrome patients (group I) by implementing an emergency
      protocol of thrombolysis by catheter-directed infusion, followed by immediate
      surgery through an anterior subclavian approach entailing (1) decompression of
      the thoracic inlet and (2) repairing the vein with a vein patch to reestablish
      its normal caliber. In addition, we treated another selective group of 81
      patients (group II) for chronic fibrotic obstruction several months after their
      original event, but only when the inflow was adequate. RESULTS: Our acute
      emergency care resulted in a 100% long-term patency rate in group I, with no
      sequelae. The patency rate in group II was 100% as well, but in 74% a long vein
      patch, endovascular stents, or homograft implants were used. CONCLUSIONS:
      Implementation of an emergency approach to treat Paget-Schroetter syndrome is
      highly recommended to prevent the delayed sequelae of permanent subclavian vein
      obliteration and disability. In chronic obstruction, when feasible, we recommend
      a long saphenous vein patch, followed by endovascular stent implant.

PMID- 19161750
TI  - Invited commentary.

PMID- 19161751
TI  - Herpes zoster after lung transplantation: incidence, timing, and outcome.
AB  - BACKGROUND: Although herpes zoster is a common complication of lung
      transplantation, the epidemiologic data are limited. The aims of the present
      study were to determine the incidence and clinical manifestations of herpes
      zoster in a large cohort of lung transplant recipients and to identify risk
      factors associated with its development. METHODS: The files of all adult patients
      who underwent lung transplantation at a major tertiary medical center from
      January 2001 to December 2007 were reviewed. Data were extracted on background,
      transplant-related, and posttransplantation factors. The occurrence and clinical
      characteristics of all episodes of herpes zoster were recorded. RESULTS: Of the
      198 lung transplant recipients, 23 had a herpes zoster infection, of whom 18 had
      herpes in a single dermatome. Disseminated cutaneous infection was documented in
      4 cases (17%) and visceral involvement in 1. The median duration of follow-up was
      34 months (range, 1 to 85 months). There were no recurrent infections.
      Postherpetic neuralgia was detected in 26% of cases. Antiviral prophylaxis,
      primarily for cytomegalovirus, was effective (during treatment) against herpes
      zoster. The incidence of herpes zoster was higher in patients treated with rabbit
      antithymocyte globulin. CONCLUSIONS: The occurrence of herpes zoster peaks
      between 12 and 36 months after lung transplantation. Additional immunosuppression
      may increase the risk. Further studies on preventive strategies against herpes
      zoster in this population are warranted.

PMID- 19161752
TI  - Minimizing endoscopic thoracic sympathectomy for primary palmar hyperhidrosis:
      guided by palmar skin temperature and laser Doppler blood flow.
AB  - BACKGROUND: Limiting the extent of sympathectomy in palmar hyperhidrosis was
      recently recognized as an effective method to minimize the incidence and severity
      of troublesome compensatory sweating. However, the levels at which transection
      should be performed remain controversial. In this study, we proposed that the
      level of ablation varies and should be adjusted for each individual patient.
      Guided by palmar skin temperature and laser Doppler blood flow, we try to find
      the correct target level in each case. METHODS: Fifty patients with severe
      primary palmar hyperhidrosis received bilateral endoscopic thoracic
      sympathectomy. Different levels of transection from T4 to T2 were performed step
      by step until the successful extirpation was implied by the intraoperative
      monitoring. The results of the operations were studied. All patients were
      followed up and evaluated for symptom resolution, postoperative complication,
      levels of satisfaction, and severity of compensatory sweating. RESULTS: Of a
      total of 100 lateral procedures, 76 laterals (76%) ended the procedure at the T4
      level, 23 laterals (23%) ended the procedure at the T3 level, and 1 lateral (1%)
      ended the procedure at the T2 level. The postoperative complication was minor,
      and no Horner's syndrome was detected. The rate of symptom resolution was 100%
      and no recurrence was found. The satisfaction rate was 92%, and the incidence of
      mild, moderate, and severe compensatory sweating were 12%, 8%, and 6%,
      respectively. CONCLUSIONS: Concerning the sympathectomy for palmar hyperhidrosis,
      there is a possibility that the level of the transection varies and should be
      adjusted for each individual patient. Intraoperative monitoring of temperature
      and blood flow may be a useful tool in establishing a kind of standardized
      reference for finding the correct target level.

PMID- 19161753
TI  - Invited commentary.

PMID- 19161754
TI  - Cardiac resynchronization therapy: long-term alternative to cardiac
      transplantation?
AB  - BACKGROUND: Cardiac transplantation remains the gold standard for treating end
      stage heart failure. However, because of donor shortage and posttransplant
      complications alternative options are needed. METHODS: We investigated the impact
      of cardiac resynchronization therapy on clinical outcome in 545 patients with
      left bundle-branch block and interventricular asynchrony, who fulfilled the
      cardiac criteria for cardiac transplantation listing. Primary end point was heart
      failure death. Secondary end points were New York Heart Association class,
      functional (cardiopulmonary exercise tolerance, 6-minute hall walk distance), and
      morphologic (left ventricular end-diastolic diameter) factors. RESULTS: The
      average follow-up period was 39.6 months (standard deviation, 26.1 months). In
      total, 1,784 years of observation were accrued. The percentage of nonresponders
      (no functional and morphologic improvement during follow-up) was 21.2%. One-year
      and 3-year freedom from heart failure death was 92.3% and 77.3%, respectively.
      Functional variables improved, but the left ventricular end-diastolic diameter
      decreased during the first 6 months of cardiac resynchronization therapy only in
      patients who survived during follow-up. Under cardiac resynchronization therapy,
      42.5% (n = 34) of the cardiac transplantation candidates with atrial fibrillation
      at baseline returned to sinus rhythm. CONCLUSIONS: Our data suggest that cardiac
      resynchronization therapy is a reliable long-term therapeutic option for the
      treatment of end-stage heart failure and intraventricular asynchrony.

PMID- 19161755
TI  - Invited commentary.

PMID- 19161756
TI  - Improved patient survival with concomitant Cox Maze III procedure compared with
      heart surgery alone.
AB  - BACKGROUND: The benefit of the Cox Maze procedure combined with heart surgery was
      evaluated at long-term follow-up. METHODS: The outcome for 37 patients who
      underwent a Cox Maze III procedure combined with heart surgery (Maze group) was
      compared with that of 66 patients who had heart surgery alone (control group).
      All patients were in persistent atrial fibrillation preoperatively. The two
      groups had similar preoperative characteristics and were operated upon during the
      same era (1996 to 2004). RESULTS: Five-year survival, including hospital deaths,
      was 89% +/- 5% in the Maze group and 60% +/- 7% in the control group (log rank p
      = 0.008). Causes of death were predominantly related to heart failure (1 of 37 in
      the Maze group and 12 of 66 in the control group; p = 0.02) and to sudden death
      (0 of 37 in the Maze group and 9 of 66 in the control group; p = 0.02). After
      correction for preoperative variables, Cox regression analysis showed that the
      Maze procedure improved survival independently (p = 0.019). In a subgroup of
      patients with left atrial diameter of more than 60 mm preoperatively, the 5-year
      survival estimate was 92% +/- 6% in the Maze group versus 59% +/- 9% in the
      control group (log rank p = 0.012). The 5-year estimate of conversion to sinus
      rhythm was 91% +/- 7% in the Maze group and 33% +/- 7% in the control group (log
      rank p < 0.001). CONCLUSIONS: The restoration of sinus rhythm by a Maze procedure
      combined with heart surgery markedly improved long-term survival in this series.

PMID- 19161757
TI  - Invited commentary.

PMID- 19161758
TI  - Levosimendan facilitates weaning from cardiopulmonary bypass in patients
      undergoing coronary artery bypass grafting with impaired left ventricular
      function.
AB  - BACKGROUND: Levosimendan is a compound with vasodilatory and inotropic
      properties. Experimental data suggest effective reversal of stunning and
      cardioprotective properties. METHODS: This prospective, randomized, placebo
      controlled, double-blind study included 60 patients with 3-vessel coronary
      disease and left ventricular ejection fraction (LVEF) of less than 0.50.
      Levosimendan administration (12 microg/kg bolus, followed by an infusion of 0.2
      microg/kg/min) was started immediately after induction anesthesia. Predefined
      strict hemodynamic criteria were used to assess the success of weaning. If
      weaning was not successful, CPB was reinstituted and an epinephrine infusion was
      started. If the second weaning attempt failed, intraaortic balloon pumping (IABP)
      was instituted. RESULTS: The groups had comparable demographics. The mean
      (standard deviation) preoperative LVEF was 0.36 (0.8) in both groups. The
      baseline cardiac index was 1.8 (0.3) L/min/m(2) in the levosimendan group and 1.9
      (0.4) L/min/m(2) in the placebo group. The mean duration of CPB to primary
      weaning attempt was 104 (25) minutes in the levosimendan and 109 (22) minutes in
      the placebo group. Primary weaning was successful in 22 patients (73%) in the
      levosimendan group and in 10 (33%) in the placebo group (p = 0.002). The odds
      ratio for failure in primary weaning was 0.182 (95% confidence interval, 0.060 to
      0.552). Four patients in the placebo group failed the second weaning and
      underwent IABP compared with none in the levosimendan group (p = 0.112).
      CONCLUSIONS: Levosimendan significantly enhanced primary weaning from CPB
      compared with placebo in patients undergoing 3-vessel on-pump coronary artery
      bypass grafting. The need for additional inotropic or mechanical therapy was
      decreased.

PMID- 19161759
TI  - Surgical ventricular restoration: left ventricular shape influence on cardiac
      function, clinical status, and survival.
AB  - BACKGROUND: Myocardial infarction can result in a spectrum of left ventricular
      (LV) shape abnormalities. Surgical ventricular restoration (SVR) can be applied
      to any, but there are no data that relate its effectiveness to LV shape.
      Moreover, there is no consensus on the benefit of SVR in patients with a markedly
      dilated ventricle, without clear demarcation between scarred and normal tissue.
      This study describes postmyocardial infarction shape abnormalities and cardiac
      function, clinical status, and survival in patients undergoing SVR. METHODS: Echo
      studies of 178 patients were retrospectively reviewed. Three types of LV shape
      abnormalities were identified: type 1 (true aneurysm), type 2 (nonaneurysmal
      lesions defined as intermediate cardiomyopathy), and type 3 (ischemic dilated
      cardiomyopathy). RESULTS: SVR induced significant improvement in cardiac and
      clinical status in all patients, regardless LV shape types. Although not
      significant, mortality was higher in types 2 and 3. CONCLUSIONS: Ischemic dilated
      cardiomyopathy and not just the true aneurysm can be successfully treated with
      SVR. Shape classification may be useful to improve patient selection and compare
      results from different institutions that are otherwise impossible to compare.

PMID- 19161760
TI  - Invited commentary.

PMID- 19161761
TI  - Prediction of survival after coronary revascularization: modeling short-term, mid
      term, and long-term survival.
AB  - BACKGROUND: Many clinical prediction rules for short-term mortality after
      coronary revascularization have been developed, validated, and introduced into
      routine clinical practice. Few rules exist for predicting long-term survival in
      the modern era of coronary revascularization. We report on the development and
      validation of models for predicting long-term survival after coronary artery
      bypass graft surgery and percutaneous coronary intervention on the basis of
      recent experience. METHODS: We linked 1987 through 2001 coronary artery bypass
      graft surgery and 1992 through 2001 percutaneous coronary intervention data from
      our northern New England registries on 35,000 patients with complete data on risk
      factors to the National Death Index, ascertaining 7,000 deaths. We partitioned
      time after revascularization into three periods on the basis of exploratory
      analysis using generalizations of Cox's semiparametric model to nonproportional
      hazards and nonlinear log-hazards. These periods were 0 to 3 months, 4 to 18
      months, and 19 months and later. For each period, Cox's regression model was used
      to regress survival on risk factors yielding three models, which were then
      combined to make long-term predictions. RESULTS: These models were incorporated
      into easy-to-use software that yields predicted survival for up to 8 years after
      revascularization. The Harrell concordance statistic ranged from 72% to 83% for
      these models. CONCLUSIONS: We developed and internally validated models that
      accurately predict long-term survival after coronary artery bypass graft surgery
      and percutaneous coronary intervention as currently performed. These models using
      routine clinical data, can be solved with available software, and could be used
      to enhance informed, patient-centered clinical decision making on the choice of
      revascularization procedure.

PMID- 19161762
TI  - Invited commentary.

PMID- 19161763
TI  - Prior inferior myocardial infarction has worse early outcomes in patients
      undergoing coronary artery bypass grafting than prior anterior myocardial
      infarction.
AB  - BACKGROUND: It is generally considered that patients with prior myocardial
      infarction (PMI) have worse outcomes than those without PMI after coronary artery
      bypass grafting (CABG). However, any difference in outcomes of patients with
      anterior or inferior PMI undergoing CABG has never been determined. METHODS: We
      retrospectively reviewed the records of 310 patients with anterior or inferior
      PMI who underwent isolated CABG between September 2004 and September 2008. Of
      these, 151 patients had anterior PMI (anterior group), and 159 patients had
      inferior PMI (inferior group). Preoperative and postoperative variables were
      compared between the groups. Multivariate logistic regression analysis was used
      to identify independent predictors of major postoperative complications including
      death. RESULTS: Patients of the inferior group were significantly older (68.3 +/-
      9.2 vs 65.5 +/- 11.0; p = 0.015) and had more diseased vessels per patient (2.9
      +/- 0.3 vs 2.8 +/- 0.5; p = 0.009) than the anterior group. A higher rate of mild
      or moderate mitral regurgitation was observed in the inferior group (18.2% vs
      8.6%; p = 0.0209). The operative mortality was higher in the inferior group (5.0%
      vs 0%; p = 0.0073). Rates of respiratory failure (6.9% vs 0.7%; p = 0.0199) and
      requirement for hemodialysis (5.7% vs 0.7%; p = 0.0056) were higher in the
      inferior group. Multivariate analysis revealed inferior PMI (p = 0.0068) as the
      only independent predictor of major postoperative complications including death.
      CONCLUSIONS: The present study indicates that patients with inferior PMI have
      poorer outcomes after isolated CABG than those with anterior PMI.

PMID- 19161764
TI  - Preoperative intraaortic balloon pumping improves outcomes for high-risk patients
      in routine coronary artery bypass graft surgery.
AB  - BACKGROUND: We evaluated the association between the preoperative use of
      intraaortic balloon pumping and in-hospital and long-term outcomes in high-risk
      patients undergoing coronary artery bypass grafting. METHODS: From 714 total
      patients undergoing coronary artery bypass grafting during a 4-year period, we
      compared the clinical, biochemical, and echocardiographic findings up to 1 year
      after surgery between 111 patients who had a European System for Cardiac
      Operative Risk Evaluation (EuroSCORE) of 12 or greater and received intraaortic
      balloon pumping preoperatively (group A) and 130 patients who had a EuroSCORE of
      5 or less and received no preoperative intraaortic balloon pumping (group B).
      RESULTS: Group A patients were significantly older, had significantly more
      comorbid conditions, and had a significantly lower mean preoperative ejection
      fraction (all p < 0.001). Intraoperative data were comparable between groups, as
      were lactate and troponin I levels sampled from the coronary sinus. Lactate,
      troponin I, creatine kinase, and creatine kinase-MB mass showed comparable
      leakage at all postoperative times. The incidences of in-hospital mortality,
      perioperative myocardial damage, and acute myocardial infarction and duration of
      hospital stay were comparable. High-risk patients showed significant improvements
      in ejection fraction (p < 0.001) and wall-motion score index (p = 0.06) after
      surgery, but low-risk patients showed no significant change in these variables.
      The incidences of death, recurrent angina, myocardial infarction, and repeat
      coronary procedures did not differ significantly between groups. CONCLUSIONS: The
      preoperative use of intraaortic balloon pumping appears to shift high-risk
      patients undergoing coronary artery bypass grafting into a lower-risk category
      and is associated with comparable perioperative troponin leakage and short-term
      and long-term outcomes similar to low-risk patients not receiving intraaortic
      balloon pumping.

PMID- 19161765
TI  - Invited commentary.

PMID- 19161766
TI  - Effects of mild hypothermia and rewarming on renal function after coronary artery
      bypass grafting.
AB  - BACKGROUND: Hypothermia is a potential strategy for visceral organ protection
      during cardiopulmonary bypass (CPB). We report data from two randomized studies
      evaluating mild hypothermia and rewarming on postoperative renal function in
      cardiac surgical patients. METHODS: Patients undergoing nonemergency, isolated
      coronary artery bypass grafting were enrolled into two studies. In the first, 223
      patients were cooled to 32 degrees C during CPB and randomly assigned to
      rewarming to 37 degrees C (RW-37 degrees) or 34 degrees C (RW-34 degrees). The
      second study randomized 267 patients to sustained mild hypothermia at 34 degrees
      C (S-34 degrees) or normothermia (S-37 degrees) without rewarming. Serum
      creatinine levels were measured. Creatinine clearance was calculated. Significant
      renal dysfunction was defined as a 25% increase in serum creatinine or a 25%
      decrease in creatinine clearance postoperatively. RESULTS: Postoperative serum
      creatinine levels were persistently higher in the RW-37 degrees patients than in
      the RW-34 degrees group (p < 0.01). RW-37 degrees patients had a higher incidence
      of renal dysfunction (17%) than RW-34 degrees patients (9%, p = 0.07). Sustained
      mild hypothermia had no beneficial effect on postoperative serum creatinine
      levels (p = 0.44) or significant renal dysfunction: S-34 degrees, 20% vs S-37
      degrees, 15% (p = 0.28). Diabetes (odds ratio [OR], 1.6; 95% confidence interval
      [CI] 1.3 to 2.1), prolonged CPB time (OR, 1.1; 95% CI, 1.0 to 1.2), and rewarming
      (OR, 1.4; 95% CI, 1.0 to 1.9) were independent risk factors for significant renal
      dysfunction. Renal dysfunction was associated with longer hospital stay (8.4 +/-
      0.8 vs 6.8 +/- 04 days, p < 0.001). CONCLUSIONS: Sustained mild hypothermia does
      not improve renal outcome. However, rewarming on CPB is associated with increased
      renal injury and should be avoided.

PMID- 19161767
TI  - Risk stratification after coronary artery bypass surgery by a point-of-care test
      of platelet function.
AB  - BACKGROUND: Aspirin is one of the main therapeutics in prevention of
      cardiovascular events due to its antiplatelet activity. However, a sufficient
      inhibition of platelet function by aspirin is not always achieved. This means
      that the extent of protection from cardiovascular event is limited. Recently,
      several studies have introduced the concept of residual platelet reactivity
      during aspirin therapy and suggested that about 40% of aspirin users may not
      respond adequately. We sought to determine whether the profile and prevalence of
      residual platelet reactivity, measured with the platelet function analyzer (PFA
      100; Dade/Behring, Marburg, Germany) device could predict a recurrent
      cardiovascular event in patients undergoing coronary artery bypass surgery.
      METHODS: A cohort of 202 consecutive patients receiving primary coronary artery
      bypass surgery during 2004 was prospectively recruited. All patients
      postoperatively received regular standard daily 100 mg aspirin. Platelet function
      was analyzed by the PFA-100 at 30 +/- 6 days after surgery. A PFA100 closure time
      less than 190 seconds was defined as residual platelet reactivity. Eighty-six
      patients (43%) showed residual platelet reactivity. The mean follow-up time was
      32 +/- 10 months and was 100% complete. RESULTS: A total of 75 cardiovascular
      events have been registered. The majority of these events were among patients
      with residual platelet activity (p = 0.001). Out of this number, graft failure
      was documented in 25 patients. The 42-month freedom from major cardiovascular
      events was significantly better for patients with adequate platelet inhibition (p
      = 0.001). At multivariable analysis residual platelet reactivity (p = 0.012),
      incomplete revascularization (p = 0.029), and diabetes (p = 0.0009) were
      independently associated with occurrence of negative events. CONCLUSIONS: Our
      results demonstrate that high residual platelet reactivity independently
      correlates with a worst clinical outcome in patients treated by coronary artery
      bypass surgery. The PFA-100 point care test could cheaply and simply discover
      this condition and contribute to improve the outcome of this subset of patients.

PMID- 19161768
TI  - Invited commentary.

PMID- 19161769
TI  - Aortic root replacement with stentless porcine xenografts: early and late
      outcomes in 132 patients.
AB  - BACKGROUND: Traditionally, aortic root replacement has most commonly involved
      mechanical composite valve grafts, which have excellent durability but
      necessitate lifelong anticoagulation. Stentless porcine xenografts (bioroots) are
      a recently developed alternative that enable root replacement without the
      necessity of long-term anticoagulation. This study examined the early and late
      outcomes of aortic root replacement with porcine bioroots. METHODS: Porcine
      bioroots were used for root replacement in 132 patients. Of these, 129 (97.7%)
      required graft extensions for ascending aortic replacement, and 55 (41.7%)
      underwent aortic arch replacement. Twenty-three operations (17.4%) were
      reoperations. Twenty-four patients (18.2%) had aortic dissection. Early and late
      outcomes were ascertained by reviewing medical records. Changes in New York Heart
      Association (NYHA) class were used to assess improvements in functional status.
      Follow-up echocardiography results were reviewed to assess bioprosthetic valve
      function and changes in left ventricular ejection fraction. RESULTS: There were
      10 operative deaths (7.6%), 9 of which were directly related to intraoperative
      ventricular failure. Nine patients (6.8%) had late valve-related complications,
      including 5 patients with prosthetic endocarditis (3 died), 1 annular
      pseudoaneurysm, and 3 sudden, unexplained deaths. Survivors' NYHA status and left
      ventricular ejection fraction improved significantly. No structural valve
      dysfunction was evident during follow-up. Actuarial survival was 85.6% +/- 3.1%
      at 1 year and 77.8% +/- 4.8% at 5 years. CONCLUSIONS: Aortic root replacement
      with porcine xenografts can be performed with respectable early and late
      outcomes, even when combined with aortic arch replacement. Further follow-up is
      necessary to evaluate long-term bioroot durability.

PMID- 19161770
TI  - A single-institution experience with the Ross operation over 11 years.
AB  - BACKGROUND: Although the Ross operation requires double-valve replacement for
      aortic valve pathology, it is the only autologous, aortic valve replacement
      available. We report a single-unit's 11-year experience. METHODS: Before August
      2006, 467 patients (mean age, 41 +/- 15 years; 358 males) underwent a Ross
      operation. The right ventricular outflow tract was repaired with a cryopreserved
      pulmonary homograft. Follow-up was 94.4% complete. RESULTS: The 30-day mortality
      was 0.6%. The Kaplan-Meier survival estimate at 120 months was 94.4% +/- 2.9%
      (standard error [SE], 0.0146). Reoperation was due to autograft failure in 15
      patients (7 repairs, 8 replacements), with a Kaplan-Meier freedom from autograft
      failure measured as reoperation or regurgitation exceeding grade II at 120 months
      of 94.2% +/- 2.8% (SE, 0.0142). Homograft replacement, mostly due to stenosis,
      occurred in 11 patients. Freedom from homograft dysfunction, defined as homograft
      reoperation or peak homograft gradient of 30 mm Hg or more, at 120 months was
      79.3% +/- 7.3% (SE, 0.0372). Freedom from all autograft- and homograft-related
      reoperations at 120 months was 85.9% +/- 6.3% (SE, 0.0321). Autograft or
      homograft endocarditis occurred in 8 patients, and 1 patient had simultaneous
      endocarditis of both valves. CONCLUSIONS: Patient survival and freedom from
      prostheses-related events over 11 years still compares favorably with
      conventional heart valve prostheses. Mortality and morbidity remain low.
      Reoperation for autograft or homograft failure is higher than our previous
      reports, and endocarditis is also evident, 1.9% (9 of 467). Homograft dysfunction
      is higher in younger recipients.

PMID- 19161771
TI  - Redo valvular surgery in elderly patients.
AB  - BACKGROUND: Elderly patients older than the age of 75 constitute 13% of the
      population that undergoes cardiac surgery at our institution and represent the
      fastest growing population in Ontario. We have witnessed an increasing proportion
      of elderly patients being referred for repeat surgical intervention for valvular
      heart disease. We determined the perioperative and long-term outcomes in elderly
      patients undergoing redo cardiac valve surgery. METHODS: A retrospective review
      of our institutional database identified 112 patients aged 75 years or older
      (mean age, 78 +/- 3 years; range, 75 to 89 years) who underwent redo valve
      surgery between 1990 and 2004. All patients presented with a previous surgical
      intervention on the valve of interest. The mean follow-up was 5 +/- 4 years and
      was 100% complete. RESULTS: Eighty-eight patients (79%) had isolated valve
      surgery at their primary operation whereas 24 patients (21%) had concomitant
      coronary artery bypass grafting at the time of their initial valve surgery. At
      reoperation, 74 patients (66%) underwent single valve surgery (40 aortic valve,
      34 mitral valve), 33 patients (29.5%) required double valve surgery, and 5
      patients (4.5%) had triple valve surgery. Thirty-three patients (29.5%) required
      concomitant coronary artery bypass grafting, among whom 14 patients had a
      previous coronary artery bypass graft surgery. There were 12 operative (10.7%)
      and 47 late deaths (42%). Cardiovascular events were the cause of death in 32
      patients (54% of all deaths). Overall survival at 5 years was 67% +/- 5%. The
      freedom from valve-related mortality and morbidity was 86% +/- 4% at 5 years.
      Mean intensive care eunit stay was 3.7 +/- 4.5 days, and postoperative hospital
      stay was 15 +/- 12 days. CONCLUSIONS: Redo valvular surgery in an elderly cohort
      can be performed with acceptable morbidity and mortality. Although 5-year
      survival is lower than that observed with a younger patient population, it is
      still likely higher than expected survival without surgical intervention. Despite
      increased resource utilization, elderly patients should be offered redo surgical
      intervention for valvular heart disease.

PMID- 19161772
TI  - Invited commentary.

PMID- 19161773
TI  - Multiple valve surgery with beating heart technique.
AB  - BACKGROUND: Multiple valve surgery was performed utilizing beating heart
      technique through simultaneous antegrade/retrograde perfusion with blood. We
      herein report our experience with this technique in patients with multiple valve
      disease processes. METHODS: Of 520 consecutive patients operated upon utilizing
      this method between 2000 and 2007, 59 patients underwent multiple valve surgery.
      Mean age was 54.2 +/- 13.8 years (range, 21 to 83) with 41 males (69.5%) and 18
      females (30.5%). Double-valve and triple-valve operations were performed in 54
      and 5 patients, respectively. RESULTS: Of 32 mitral valve replacements, there
      were 30 biological (93.8%) and 2 mechanical (6.2%) mitral valves. Aortic valve
      replacement was performed in 25 patients: 22 (88%) with biological and 3 (12%)
      with mechanical prostheses. Two patients had mitral and tricuspid valve repair.
      The most common procedure was mitral valve replacement plus tricuspid valve
      repair (16 patients; 27.1%), mitral valve replacement plus aortic replacement (14
      patients; 23.7%), and mitral valve repair plus tricuspid repair (13 patients;
      22%). Concomitant coronary artery bypass grafting was performed in 7 (11.8%) of
      59 patients. Mean hospital stay was 25.6 +/- 29.6 days (range, 3 to 195; median,
      17). Early mortality (less than 30 days) occurred in 5 patients (8.4%), and late
      mortality (more than 30 days) occurred in 2 patients (3.4%). Reoperation for
      bleeding was needed in 5 patients (8.4%). Intra-aortic balloon pump was required
      preoperatively and postoperatively in 4 and 1 patients, respectively. Clinical
      and echocardiographic follow-up in 33 patients at 11.8 +/- 16.4 months (range, 1
      to 80) showed preserved postoperative left ventricular ejection fraction. Three
      patients had perivalvular leaks on follow-up but required no surgery. Nineteen
      patients were lost to follow-up. CONCLUSIONS: This study demonstrates the
      feasibility and safety of beating heart techniques in multiple valve operations.
      Further studies are needed to fully evaluate the potential benefits of this
      method of myocardial perfusion as a means to eliminate ischemia-reperfusion
      injury, and to preserve ventricular function in multiple valvular surgery.

PMID- 19161774
TI  - Blood transfusion reduction in cardiac surgery: multidisciplinary approach at a
      community hospital.
AB  - BACKGROUND: Mounting evidence exists for more restrictive blood transfusion
      practices in patients undergoing cardiac surgery. Few studies, however, have
      recognized or agree upon a method by which this decrease in allogeneic red blood
      cell transfusion can be achieved. We will review our methods and experience in a
      blood conservation initiative from 2003 to 2007. METHODS: A data driven,
      multidisciplinary effort to decrease allogeneic red blood cell transfusion was
      instituted in a community hospital. Numerous innovations in treatment protocols
      were implemented and evaluated. Clinical data from 2003 to 2007 will be
      presented. Yearly review of outcomes led to an evolving clinical practice and
      lowered transfusion rates. RESULTS: A total of 2,531 consecutive cardiac surgical
      procedures were performed during a five-year period. Using a multidisciplinary
      approach to quality improvement, and with the goal of using fewer blood products,
      our incidence of allogeneic red blood cell transfusion was decreased, from 43% in
      2003 to 18% in 2007. Patient outcomes were not significantly changed.
      CONCLUSIONS: Cardiac surgery in a community hospital can be performed safely with
      low utilization of allogeneic red blood cell transfusions. A multidisciplinary
      approach to blood conservation can result in lower transfusion rates and
      equivalent patient outcomes.

PMID- 19161775
TI  - Is cardiac surgery safe in extremely obese patients (body mass index 50 or
      greater)?
AB  - BACKGROUND: We investigated the impact of extreme obesity (body mass index
      [kg/m(2)] 50 or greater) on short-term clinical outcomes and report 1-year
      mortality. METHODS: Fifty-seven patients were found to have a body mass index of
      50 or greater among 14,449 patients who underwent cardiac surgery between July
      2000 and June 2007. Multivariable logistic regression analyses were used to
      assess the independent influence of extreme obesity on the major outcomes.
      RESULTS: Of the 57 patients, the mean age was 58 +/- 11 years, mean body mass
      index was 55.1, and 63% of the patients were women. Forty patients underwent
      elective surgery. Forty-one patients had isolated coronary artery bypass graft
      surgery. The overall operative mortality was 9%; the mortality was 5% in isolated
      coronary artery bypass graft surgery and 5% in elective surgery. Fifteen patients
      had nonelective isolated coronary artery bypass graft surgery, and 2 patients had
      emergent active endocarditis surgery. Off-pump coronary artery bypass graft
      surgery was performed on 23 patients (23 of 41, 54%). After adjusting for known
      preoperative and operative risk factors through a multivariate logistic model,
      extreme obesity did not emerge as a significant risk factor for operative
      mortality (odds ratio, 1.75; p = 0.47) and other adverse outcomes (p > 0.05)
      after elective surgery; however, extreme obesity was marginally associated with
      increased mortality (odds ratio, 2.69; p = 0.05) and was a risk predictor for
      longer intensive care unit stays (odds ratio, 2.43; p = 0.01) in overall surgery.
      The 1-year survival rate was 82.5%. CONCLUSIONS: Extreme obesity is not a
      contraindication to elective cardiac surgery. Studies stratifying the risk
      factors of mortality for nonelective surgery in extremely obese patients may be
      warranted.

PMID- 19161776
TI  - Invited commentary.

PMID- 19161777
TI  - Inclusion of hepatic venous drainage in patients with pulmonary arteriovenous
      fistulas.
AB  - BACKGROUND: It is well known that hepatic vein (HV) inclusion can ameliorate
      cyanosis in patients with pulmonary arteriovenous fistulas (PAVFs) during the
      sequence of Fontan type repair. Previously, we reported that most patients with
      bidirectional cavopulmonary shunt (BCPS) have clinical or subclinical evidence of
      a right to left shunt through PAVFs. METHODS: We studied 33 patients who already
      had clinical and subclinical PAVFs after BCPS. All patients have taken Fontan
      completion with HV inclusion. The state of PAVFs was reevaluated by pulmonary
      angiogram, contrast echocardiography, and lung scintigraphy 7.7 +/- 2.4 years
      after HV inclusion. RESULTS: After Fontan completion, the mean oxygen saturation
      increased from 80.2 +/- 7.4% to 91.5 +/- 9.8% in the entire cohort. Moreover, the
      amount of right-to-left shunting through the PAVFs, measured by lung
      scintigraphy, was decreased from a mean of 23.8 +/- 15.1 to 13.0 +/- 8.2%. The
      degree of severity, for most patients, was decreased as demonstrated by contrast
      echocardiography. However, 5 patients (16.7%) showed persistent PAVFs, even after
      the HV inclusion. They all had left isomerism with azygous continuation of the
      IVC and the conduit was positioned on the contralateral side to the SVC with
      azygous drainage. CONCLUSIONS: Most PAVFs regressed after Fontan completion. Left
      isomerism with azygous continuation of the IVC had risk for persistent PAVFs when
      the HV conduit was positioned at the contralateral side to the SVC receiving the
      azygous drainage. Therefore, appropriate design avoiding unilateral streaming of
      HV flow should be considered for HV inclusion surgery.

PMID- 19161778
TI  - Invited commentary.

PMID- 19161780
TI  - Midterm to long-term outcome of total cavopulmonary connection in high-risk adult
      candidates.
AB  - BACKGROUND: Adult patients who do not fulfill the classical Fontan criteria now
      undergo total cavopulmonary connection (TCPC). However, limited information is
      available on the results for high-risk adult TCPC. METHODS: Twenty-five
      consecutive adult patients (aged 16 years or more) who underwent TCPC were
      retrospectively reviewed. The mean age at operation was 27 +/- 9 years (range, 16
      to 52). The following items were considered as the potential risk factors
      according to previous reports: (1) aged more than 30 years (7 of 25); (2)
      heterotaxy (9 of 25); (3) systemic ventricular ejection fraction less than 50% (6
      of 25); (4) atrioventricular valve regurgitation moderate or greater (6 of 25);
      (5) pulmonary arterial index less than 200 (7 of 25); (6) mean pulmonary arterial
      pressure 15 mm Hg or greater (3 of 25); (7) pulmonary arterial resistance 2.0
      wood units or greater (11 of 25); (8) arrhythmias (13 of 25); (9) protein-losing
      enteropathy (3 of 25); (10) New York Heart Association (NYHA) functional class
      III or greater (9 of 25); (11) previous Fontan procedure (10 of 25); (12)
      systemic ventricular outflow obstruction (1 of 25); and (13) end-diastolic
      pressure of the systemic ventricle 11 mm Hg or higher (4 of 25). RESULTS: The
      mean follow-up period was 57 +/- 45 months (range, 0 to 154). All patients had at
      least 2 risk factors (range, 2 to 8). There was 1 early death and 2 late deaths.
      Comparing the late survivors and nonsurvivors, no statistical significance was
      identified in the above risk factors. However, the patients with 6 or more risk
      factors had a significantly higher mortality rate than patients with fewer than 6
      risk risk factors (p < 0.01). Age (p = 0.08), NYHA class (p = 0.13), and protein
      losing enteropathy (p = 0.08) may be risk factors for late death. CONCLUSIONS:
      The majority of the adult TCPC candidates tolerated the TCPC procedure in the
      early postoperative period. However, the accumulation of risk factors influences
      late mortality.

PMID- 19161779
TI  - Impact of age at Fontan completion on postoperative hemodynamics and long-term
      aerobic exercise capacity in patients with dominant left ventricle.
AB  - BACKGROUND: Although the Fontan procedure is now being applied to younger
      patients, the influence of patients' age at the time of surgery on long-term
      results remains unclear. We investigated whether age at Fontan completion affects
      subsequent hemodynamics and exercise capacity in patients with a dominant left
      ventricle followed up for more than 5 years. METHODS: Between January 1990 and
      December 2001, 68 patients with a dominant left ventricle underwent total
      cavopulmonary connection (TCPC) at our institute. The survivors routinely
      underwent postoperative exercise tests and catheterization at 1 year and then
      every 5 years after TCPC, and were divided into group A (< 3 years; n = 32) and
      group B (> or = 3 years; n = 33), according to age at time of the Fontan
      procedure and retrospectively reviewed. We also examined the correlation between
      age at Fontan and data from postoperative catheterization or exercise tests.
      RESULTS: None of the patients died during a follow-up period of 91.2 +/- 46.7
      months. The postoperative exercise capacity (peak oxygen consumption; % of normal
      [61.3 +/- 11.5 versus 51.9 +/- 9.1, p = 0.0001]), cardiac index at 5 years (3.31
      +/- 0.62 versus 2.86 +/- 0.69, p = 0.0133) and at 10 years after TCPC (3.24 +/-
      0.46 versus 2.61 +/- 0.65, p = 0.0194), and ventricular ejection fraction (%) at
      10 years after TCPC (62.1 +/- 7.6 versus 53.0 +/- 8.0, p = 0.0131) were
      significantly higher in group A. Age at Fontan completion inversely correlated
      with postoperative peak oxygen consumption (R = -0.374, p = 0.0006) and cardiac
      index at 5 years (R = -0.452, p = 0.0003) and 10 years after TCPC (R = -0.491, p
      = 0.0072). CONCLUSIONS: Earlier TCPC is beneficial in the long term from the
      viewpoint of exercise capacity and hemodynamics among patients with a dominant
      left ventricle.

PMID- 19161781
TI  - Near-infrared spectroscopy in neonates before palliation of hypoplastic left
      heart syndrome.
AB  - BACKGROUND: Neonates with hypoplastic left heart syndrome have circulatory
      vulnerability that results in shock and high risk of mortality without
      intervention. High arterial saturation (SaO(2)) is often used as a proxy for
      inadequate systemic oxygen delivery and triggers the use of invasive therapies to
      restore circulatory balance. We hypothesized that preoperative use of near
      infrared spectroscopy (NIRS) would reduce the need for invasive therapies,
      including controlled ventilation and inspired gas manipulation. METHODS: A Human
      Research Review Board-approved retrospective review of patients who had stage 1
      palliation from January 2000 to January 2006 was conducted. Preoperative patient
      characteristics, cardiorespiratory support, and monitored data were collected for
      all patients. Cerebral and somatic tissue oxyhemoglobin saturations were recorded
      for patients with preoperative NIRS monitoring. RESULTS: The studied cohort
      included 92 patients, 47 without and 45 with preoperative NIRS. Patient
      characteristics were similar between groups. Differences were observed in
      preoperative respiratory support. Controlled ventilation was less common in the
      NIRS group (51% versus 79%, p = 0.005) as was the use of inspired nitrogen (16%
      versus 70%, p = 0.001). The NIRS patients had higher mean SaO(2) (92% versus 88%,
      p = 0.001). Age at surgery was similar between groups (5.7 +/- 3.2 versus 6.5 +/-
      5.2 days, p = 0.3). Early survival was 96% in each group. CONCLUSIONS: Near
      infrared spectroscopy monitoring of patients with hypoplastic left heart syndrome
      awaiting palliation provides noninvasive assessment of oxygen delivery and
      simplified management, with reduced use of controlled ventilation and inspired
      gas. Higher SaO(2) in the NIRS group was not associated with impaired systemic
      oxygen delivery, and did not lead to earlier palliation or postoperative
      mortality.

PMID- 19161782
TI  - Analysis of arrhythmias after correction of partial anomalous pulmonary venous
      connection.
AB  - BACKGROUND: Several methods for surgical repair of partial anomalous pulmonary
      venous connection have been described. Sinus node dysfunction is known as a cause
      of morbidity after surgical repair. In this retrospective study, we attempted to
      determine the incidence of arrhythmias after use of two different techniques for
      repair of partial anomalous pulmonary venous connection. METHODS: Between 1988
      and 2006, 119 patients (61 male, 58 female; aged 5 months to 66 years) with
      anomalous drainage of the pulmonary vein into the superior vena cava or the right
      atrium were analyzed. All patients had sinus rhythm before operation. In 64
      patients (group 1), rerouting of the pulmonary veins was accomplished through a
      right atriotomy; and in 54 patients (group 2), the atriotomy incision was
      extended into the superior vena cava through the cavoatrial junction. RESULTS:
      There were no perioperative deaths. New-onset nodal rhythm and atrial
      dysrhythmias developed significantly more often in patients with extended
      incision through the cavoatrial junction (group 1, 26.5%, versus group 2, 54.5%;
      p < 0.004). At discharge, the rate of dysrhythmias was 14% in group 1 and 32.7%
      in group 2 (p < 0.01). The hospital stay was longer in group 2. At 1-year follow
      up of 58 patients, the rate of arrhythmias was 6.25% in group 1 versus 18.1% in
      group 2. CONCLUSIONS: Extended incision through the cavoatrial junction increases
      atrial dysrhythmias, especially early postoperatively, but the incidence of such
      sinus node dysfunction decreased with time.

PMID- 19161783
TI  - Monitoring risk-adjusted outcomes in congenital heart surgery: does the
      appropriateness of a risk model change with time?
AB  - BACKGROUND: Risk adjustment of outcomes in pediatric congenital heart surgery is
      challenging due to the great diversity in diagnoses and procedures. We have
      previously shown that variable life-adjusted display (VLAD) charts provide an
      effective graphic display of risk-adjusted outcomes in this specialty. A question
      arises as to whether the risk model used remains appropriate over time. METHODS:
      We used a recently developed graphic technique to evaluate the performance of an
      existing risk model among those patients at a single center during 2000 to 2003
      originally used in model development. We then compared the distribution of
      predicted risk among these patients with that among patients in 2004 to 2006.
      Finally, we constructed a VLAD chart of risk-adjusted outcomes for the latter
      period. RESULTS: Among 1083 patients between April 2000 and March 2003, the risk
      model performed well at predicted risks above 3%, underestimated mortality at 2%
      to 3% predicted risk, and overestimated mortality below 2% predicted risk. There
      was little difference in the distribution of predicted risk among these patients
      and among 903 patients between June 2004 and October 2006. Outcomes for the more
      recent period were appreciably better than those expected according to the risk
      model. This finding cannot be explained by any apparent bias in the risk model
      combined with changes in case-mix. CONCLUSIONS: Risk models can, and hopefully
      do, become out of date. There is scope for complacency in the risk-adjusted audit
      if the risk model used is not regularly recalibrated to reflect changing
      standards and expectations.

PMID- 19161784
TI  - Invited commentary.

PMID- 19161785
TI  - Central pulmonary artery histopathology in patients with cyanotic congenital
      heart diseases.
AB  - BACKGROUND: This study evaluated the pulmonary arterial (PA) wall histopathology
      and the risk factors related to histopathology and inadequate pulmonary artery
      growth in patients with cyanotic congenital heart diseases (CHDs) undergoing
      primary or second-stage operations after different types of systemic-to-PA shunts
      with or without pulmonary arterioplasty. METHODS: Operatively excised full
      thickness PA tissue from 150 consecutive patients (mean age, 90.8 +/- 62.8
      months; range, 6 months to 47 years) undergoing primary or second-stage
      procedures for different cyanotic CHDs were studied by light microscopy. The
      controls were 43 patients (23.8%) with normally developed central PAs and normal
      wall histology. RESULTS: The incidence of elastic fragmentation, increased ground
      substance, smooth muscle disarray, intimal thickening, and fibrosis was 61.3%,
      36.6%, 34.6%, 39.3%, and 42% respectively. The risk of inadequate PA growth was
      174.8, 64.7, and 45.5 times higher in patients with muscle disarray of the PA,
      abnormal lamellar count, and absence of palliative shunting procedures.
      CONCLUSIONS: Almost all PA walls in shunted patients undergoing primary/second
      stage procedures for cyanotic CHD indicate significant lamellar loss and
      intrinsic pulmonary arteriopathy. These changes are present in infancy, are more
      pronounced in patients with deep cyanosis, and may account for or may coexist
      with a higher incidence of PA hypoplasia and inadequate PA growth encountered in
      these patients.

PMID- 19161786
TI  - Invited commentary.

PMID- 19161787
TI  - Off-pump pulmonary valve implantation of a valved stent with an anchoring
      mechanism.
AB  - PURPOSE: The purpose of this study was to evaluate the longitudinal performance
      and anti-migration effect of a bovine valved stent equipped with an anchoring
      mechanism implanted off-pump in the pulmonary position. DESCRIPTION: Through a
      delivery system, the bell-shaped pulmonary valved stents were implanted off-pump
      in the pulmonary valve position into six sheep by the transventricular approach.
      Hemodynamic, angiographic, and echocardiographic evaluations were carried out
      before, immediately after, and 2 months after implantation. Macroscopic and
      radiographic examination were performed for evaluation. EVALUATION: The valved
      stents were all successfully implanted off-pump in the pulmonary position on six
      sheep. Early and late angiographic, echocardiographic, hemodynamic, and
      macroscopic studies confirmed firm anchoring and good positions of the stents.
      All valved stents were potent, except one mild stenosis with a 24 mm Hg
      transvalvular pressure gradient that developed and one mild insufficiency that
      were discovered at the end of the study. CONCLUSIONS: Transventricular
      implantation of the bell-shaped pulmonary valved stents was evaluated during a 2
      month period in the sheep in the present study and showed a good structural and
      functional outcome with no migration.

PMID- 19161788
TI  - Invited commentary.

PMID- 19161789
TI  - Endovascular aortic arch repair after aortic arch de-branching.
AB  - PURPOSE: Conventional surgical therapy of aortic arch aneurysms consists of
      aortic arch replacement requiring cardiopulmonary bypass and deep hypothermic
      circulatory arrest. This method is associated with significant morbidity and
      mortality, mainly due to neurologic complications and the sequelae of deep
      hypothermic circulatory arrest. Thus, it makes sense to work on developing less
      invasive surgical techniques. DESCRIPTION: Surgical aortic arch de-branching is
      required before the supra-aortic vessels can be safely covered by an endovascular
      stent graft. We describe how the supra-aortic vessels can best be revascularized,
      followed by complete coverage of the aortic arch with endovascular stent grafts.
      EVALUATION: We hereby present our case selection criteria, preoperative work-up,
      and surgical approach for aortic arch de-branching with supra-aortic
      revascularization, followed by complete coverage of the aortic arch by
      endovascular stent grafting. This technique's safeguards and pitfalls are
      described for a cohort of 26 patients. CONCLUSIONS: Endovascular aortic arch
      repair after aortic arch de-branching has the potential to lower the morbidity
      and mortality rates in patients with aortic arch diseases.

PMID- 19161790
TI  - Invited commentary.

PMID- 19161791
TI  - Tracheal reconstruction with the use of radial forearm free flap combined with
      biodegradative mesh suspension.
AB  - The main aim of tracheal restoration is to provide a noncollapsible construction
      with a functional epithelial lining and well-vascularized coverage. The authors
      present the case of a successful tracheal reconstruction in a patient with
      recurrent thyroid gland cancer infiltrating the trachea. The free radial forearm
      flap was formed as a tube and suspended to the mesh rings placed outside.
      Currently the patient has no problems with breathing.

PMID- 19161792
TI  - Inflammatory myofibroblastic tumor in the airway of a child.
AB  - This report describes a 9-year-old boy who was found to have an inflammatory
      myofibroblastic tumor completely occluding the right mainstem bronchus. Initial
      subtotal resection at an outside facility resulted in prompt recurrence of the
      tumor. At our institution, total resection with bronchotomy and pericardial patch
      repair resulted in an excellent outcome with no evidence of recurrence at 1 year
      post-resection.

PMID- 19161793
TI  - Consequences of a wait-and-see strategy for benign metastasizing leiomyomatosis
      of the lung.
AB  - Pulmonary benign metastasizing leiomyomatosis (BML) is a rare smooth-muscle cell
      disorder of the lung. Most BML lesions stay constant in size for a long time. The
      prevailing treatment option is primary excision of the nodules or if
      unresectable, long-time hormone therapy. Herein, we present a case of BML in
      which a wait-and-see strategy after diagnosis was decided. Fourteen years later a
      routine chest roentgenogram revealed multiple bi-lobar BML lesions with a giant
      cyst filling the whole left lung cavity. We conclude that a wait-and-see
      procedure for BML is feasible, but primary resection of the BML tumor masses is
      preferable to avoid complications as described in our case.

PMID- 19161794
TI  - Placental transmogrification of the lung presenting as emphysema and a lung mass.
AB  - Placental transmogrification of the lung is a rare histologic subtype of bullous
      emphysema. We report a case of placental transmogrification in a 39-year-old man
      with dyspnea, mild hemoptysis, and giant bullous emphysema with an associated
      lung mass. Here we show that untreated placental transmogrification of the lung
      can lead to severe pulmonary symptoms and surgery is diagnostic and curative.

PMID- 19161795
TI  - Atypical presentation of extranodal Rosai-Dorfman disease.
AB  - We describe a 42-year-old woman with progressive dyspnea on exertion resulting
      from pulmonary artery compression by a mediastinal mass due to extranodal Rosai
      Dorfman disease. After initial biopsies were inconclusive, she underwent surgical
      resection of the mass to relieve the pulmonary artery compression, which was
      causing severe right ventricular dysfunction. Debulking of the mass required
      resection and reconstruction of the ascending aorta, pulmonary trunk, and
      bilateral pulmonary arteries using cardiopulmonary bypass and circulatory arrest.
      We believe this is the first report of Rosai-Dorfman disease manifesting as
      compression of the thoracic great vessels.

PMID- 19161796
TI  - Severe valvular regurgitation and late prosthesis embolization after percutaneous
      aortic valve implantation.
AB  - We report the case of a 79-year-old man with low-flow, low-gradient aortic
      stenosis who underwent transapical aortic valve implantation. The deployment of a
      26-mm Edwards SAPIEN valve (Edwards Lifesciences Inc, Irvine, CA) was complicated
      with the occurrence of severe central aortic regurgitation that was successfully
      treated with the implantation of a second valve ("valve-in-valve"). Postoperative
      progress was satisfactory but 2 days after the procedure he suddenly developed
      cardiogenic shock secondary to the migration of the aortic bioprothesis into the
      left ventricular outflow tract. Open-heart surgery was undertaken to remove the
      valves and perform standard aortic valve replacement, but the patient died
      perioperatively.

PMID- 19161797
TI  - Triple aortic root injury.
AB  - Nonpenetrating aortic root injuries, including aortic transection, coronary
      artery dissection, and aortic valve disruption, are very rarely seen and
      difficult to diagnose. This case was determined to be a combination of all three
      of these injuries. The management of this patient's injuries was also a challenge
      because of a history from previous drug-eluting stent implantation.

PMID- 19161798
TI  - Entire stent grafting of the thoracoabdominal aorta in a renal transplant
      recipient subsequent to extra-anatomical bypasses of the main abdominal vessels.
AB  - We present a complex case of a renal transplant recipient with ruptured
      suprarenal abdominal aortic aneurysm who had previously undergone endovascular
      repair of descending thoracic and abdominal aortic aneurysm. This patient was
      treated successfully combining extra-anatomical bypasses of main abdominal
      arteries and subsequent endovascular stent grafting covering the entire
      thoracoabdominal aorta.

PMID- 19161799
TI  - Fabry disease with aortic regurgitation.
AB  - Aortic regurgitation is not so rare in patients with Fabry disease. Enzyme
      replacement therapy has become the standard medical care for Fabry disease in
      recent years. A 31-year-old man with Fabry disease, treated with recombinant
      alpha-galactosidase enzyme replacement for 19 months was admitted for evaluation
      of exertional dyspnea. Cardiac workup revealed left ventricular hypertrophy,
      increased left ventricular size, and moderate to severe aortic regurgitation. He
      underwent mechanical valvular replacement and heart biopsy. Histology of his
      aortic valve showed myxoid degeneration of valve leaflets. His heart muscle
      revealed extensive hypertrophy with vacuolization and the absence of lamellar
      bodies. We report a case of Fabry disease with aortic regurgitation in a man who
      underwent valvular replacement operation during enzyme replacement therapy.

PMID- 19161800
TI  - A 37-year-old Smeloff-Cutter aortic valve.
AB  - We describe the case of a 64-year-old woman with mitral insufficiency that had
      undergone an aortic valve replacement with a Smeloff-Cutoff prosthesis (Cutter
      Laboratories, Berkeley, CA) 37 years ago. She underwent both aortic and mitral
      valve replacement. The patient's Smeloff-Cutter aortic valve was unchanged. This
      case demonstrates the longest durability for the Smeloff-Cutter aortic prosthesis
      reported in the literature.

PMID- 19161802
TI  - Recurrent ventricular arrhythmia after coronary artery bypass grafting treated
      with radiofrequency catheter ablation.
AB  - A 63-year-old diabetic woman was emergently submitted to coronary artery bypass
      grafting in the setting of acute myocardial infarction. Recurrent, drug
      refractory episodes of ventricular arrhythmia occurred for 2 weeks
      postoperatively, despite no documentation of ongoing myocardial ischemia and
      optimum medical treatment. Ventricular arrhythmia was initiated by premature
      ventricular contractions originating from the Purkinje system within the infarct
      border zone. Radiofrequency catheter ablation was performed at sites where
      Purkinje potentials were recorded, leading to arrhythmia cessation. A week later,
      an implantable cardioverter defibrillator was inserted and she was discharged
      home a few days later. At 15-month follow-up, there were no further episodes of
      arrhythmia and ventricular function had improved.

PMID- 19161801
TI  - Acute profound thrombocytopenia after treatment with tirofiban and off-pump
      coronary artery bypass grafting.
AB  - The glycoprotein IIb/IIIa (GP IIb/IIIa) receptor antagonists prevent platelet
      aggregation and thrombus formation, improving outcomes of patients with acute
      coronary syndrome. Therapy with these agents may lead to bleeding complications
      and thrombocytopenia, challenging the perioperative management of patients
      undergoing coronary surgery. We report the successful management of an acute
      profound thrombocytopenia after urgent off-pump coronary surgery in a patient
      treated with tirofiban for unstable angina and acute coronary syndrome.

PMID- 19161803
TI  - Massive alterations of the left internal thoracic artery late after repair for
      aortic coarctation.
AB  - Adhesions or unattended injury are known but are seldom reasons to prevent
      withdrawing the use of the left internal thoracic artery during coronary artery
      bypass grafting. The patient in this case report was a 68-year-old man, who had
      undergone repair for aortic coarctation 34 years prior to coronary artery bypass
      grafting. After left internal thoracic artery harvesting, a no-flow situation of
      the graft was present. Transection of the graft revealed massive atherosclerotic
      alterations. To avoid unnecessary left internal thoracic artery harvesting,
      preoperative imaging in terms of a left internal thoracic artery angiography
      during coronary angiography is mandatory. The fact of finding massive alterations
      decades after pressure reduction indicates that relief from shear stress is not
      necessarily combined with remodeling of vascular alterations.

PMID- 19161804
TI  - Emergency surgery for acute mitral valve obstruction resulting from hemorrhage
      within a left atrial myxoma.
AB  - Left atrial myxomas are benign, slow-growing primary cardiac tumors. They present
      with gradual onset of one or more of a triad of obstructive, embolic, or
      constitutional symptoms. Transesophageal echocardiography aids in the detailed
      preoperative and intraoperative evaluation of the myxoma for surgical strategy
      planning. We describe a previously unreported case of interstitial hemorrhage in
      a left atrial myxoma leading to rapid expansion of the tumor with features of
      acute, mitral valve obstruction. Transesophageal echocardiography showed a cystic
      area in the left atrial tumor that corresponded to an area of recent hemorrhage
      confirmed on surgical removal.

PMID- 19161805
TI  - Blood cyst of the right ventricle presenting as recurrent high fever and chills
      in an adult.
AB  - Blood cysts are uncommon primary cardiac tumors, frequently encountered in
      pediatric patients, but extremely rare when found in adults. Due to the
      considerable risks of embolization and obstruction of the blood flow, surgical
      removal is preferred. Herein, we report a case of blood cyst of the right
      ventricle, presenting as recurrent fever and chills in an adult patient.

PMID- 19161806
TI  - Use of methylene blue for catecholamine-refractory vasoplegia from protamine and
      aprotinin.
AB  - We present two cases of catecholamine-refractory and vasopressin-refractory
      vasoplegic syndrome associated with intraoperative anaphylaxis during cardiac
      surgery. One case was related to the administration of protamine and the other
      case to the administration of aprotinin. Both cases were successfully managed
      using intravenous methylene blue. The use of methylene blue blocks accumulation
      of cyclic guanosine monophosphate by competitively inhibiting the enzyme
      guanylate cyclase. This results in reduced responsiveness of the vasculature to
      cyclic guanosine monophosphate-mediated vasodilators, such as nitric oxide. This
      report provides a description of severe anaphylaxis induced by different agents,
      in which the use of methylene blue was associated with a significant clinical
      response.

PMID- 19161807
TI  - Early constrictive epicarditis after coronary artery bypass surgery.
AB  - A patient with constrictive pericarditis early after coronary bypass surgery is
      presented. At reoperation a dense inflammatory process was encountered on the
      epicardial surface of the heart with minimal pericardial thickening.
      Crosshatching of the epicardial scar tissue produced an immediate and durable
      clinical response.

PMID- 19161808
TI  - Giant thymolipoma causing cardiocompressive syndrome with chronic heart failure.

PMID- 19161809
TI  - Severe right atrial obstruction due to cardiac extension of a hepatic carcinoma.

PMID- 19161810
TI  - Aortic valve commissural fenestrations due to sinus of valsalva dilatation.

PMID- 19161811
TI  - Esophagectomy and gastric pull-up in patients with previous free jejunal
      transfer.
AB  - Several options exist for reconstruction after total esophagectomy in patients
      with esophageal carcinoma. However, the options for a major resection after
      previous head and neck surgery in these patients are extremely limited. The
      procedure performed in 2 patients requiring esophagectomy after resection for
      previous head and neck malignancies is described. Both patients underwent
      previous chemoradiation therapy and free jejunal transfer for hypopharyngeal
      squamous cell carcinoma. Esophagectomy and reconstruction with a cervical
      gastrojejunal anastomosis combined with deltopectoral flaps were performed after
      the diagnosis of esophageal disease. Soft tissue defects were closed with a
      modified deltopectoral flap using de-epithelization. The deltopectoral flap is
      effective not only for cutaneous resurfacing, but also to promote delayed wound
      healing after radiation therapy. This report demonstrates a useful
      multidisciplinary approach for resection and reconstruction in patients after a
      previous free jejunal transfer.

PMID- 19161812
TI  - Alternative method for cardiac resynchronization: transapical lead implantation.
AB  - Alternative methods are necessary for cardiac resynchronization therapy when
      coronary sinus lead implantation fails. We aim to describe a fundamentally new
      approach using transapical implantation of an active fixation endocardial pacing
      lead. This technique is based on direct puncture of the left ventricular apex
      using the standard Seldinger technique. The tip of the lead is positioned with
      intracavital navigation under fluoroscopy. This method offers advantages for
      cardiac resynchronization because it is minimally invasive, provides endocardial
      pacing, and does not involve the mitral valve.

PMID- 19161813
TI  - Replacement of A2 and A3 by pericardium due to endocarditis of the anterior
      leaflet of the mitral valve.
AB  - We present a case of acute endocarditis due to enterococcus faecalis involving
      partially A2 and completely A3 (Carpentier classification) with destruction of
      the free margin of the mitral valve. Repair was performed by using glutaraldehyde
      treated porcine pericardium to replace the defect and neochordae of
      polytetrafluoroethylene sutured to the free margin of the pericardium to achieve
      competence. Intraoperative and follow-up echocardiogaphies showed no
      regurgitation.

PMID- 19161814
TI  - Exploring the association between elevated body mass index and Barrett's
      esophagus: a systematic review and meta-analysis.
AB  - We performed a systematic review and meta-analysis to study the association
      between elevated body mass index (BMI) and Barrett's esophagus (BE). Cross
      sectional, case-control and cohort studies published through February 2008 that
      met strict inclusion and exclusion criteria were included. Summary estimates were
      calculated for the association between BE and being either overweight (BMI > or =
      25 kg/m(2)) or obese (BMI > or = 30 kg/m(2)), or both. Based on 11 studies
      included in this analysis, there was a statistically significant relationship
      between increasing BMI and BE. Further studies are needed to evaluate if the
      presence of reflux attenuates the strength of this relationship, and if a
      particular pattern of obesity is more strongly associated with BE.

PMID- 19161815
TI  - The Society of Thoracic Surgeons practice guideline series: Blood glucose
      management during adult cardiac surgery.

PMID- 19161816
TI  - Citation of retracted articles: a call for vigilance.

PMID- 19161817
TI  - Cardiopulmonary exercise testing accurately predicts risk of major surgery
      including esophageal resection: letter 1.

PMID- 19161819
TI  - The importance of cardiopulmonary exercise testing in the prediction of surgical
      risk: letter 2.

PMID- 19161820
TI  - Postoperative ischemia and cognitive impairment in cardiac surgery patients.

PMID- 19161822
TI  - Takotsubo syndrome and the cardiac surgery patient.

PMID- 19161824
TI  - Off-pump coronary bypass surgery: another brick in the wall of reduced graft
      patency.

PMID- 19161825
TI  - Predicting complications of top hat prosthesis in aortic valve replacements:
      suspicion can save lives.

PMID- 19161827
TI  - Aortic origin of the right pulmonary artery: surgical techniques and outcome.

PMID- 19161829
TI  - A nos lecteurs.

PMID- 19161830
TI  - The inspection paradox and whole-genome analysis.
AB  - One of the major challenges of modern biology is distinguishing meaningful
      patterns from the random fluctuations of DNA sequences resulting from chromosome
      shuffling in each generation. A disease-causing mutation is more likely to be
      found in a large recombination interval. The paradoxical observation that causal
      genetic variants are more likely to be found in larger intervals is a consequence
      of sampling bias and is known as the inspection paradox. According to this
      paradox, the interval containing a fixed point (the causal gene variant) is
      around double the length of an interval not subject to this constraint, but this
      average doubling of length is attenuated or neutralized at the ends of
      chromosomes, where the distribution of interval sizes gradually returns to
      normal. This prediction is experimentally testable. The consequences of sampling
      biases for haplotype patterns are small in large studies of many families, but
      may be more marked when trying to counsel an individual family, because the
      doubling of the size of segments is only a large-number average, and the effect
      may be much larger for an unusual number of recombination events. The challenge
      of identifying a causal signature from haplotype patterns is illustrated by the
      problem of the proportion of X-linked mutations in pairs of affected brothers.

PMID- 19161832
TI  - Phylogeny of Tec family kinases identification of a premetazoan origin of Btk,
      Bmx, Itk, Tec, Txk, and the Btk regulator SH3BP5.
AB  - It is generally considered mammals and birds have five Tec family kinases (TFKs):
      Btk, Bmx (also known as Etk), Itk, Tec, and Txk (also known as Rlk). Here, we
      discuss the domains and their functions and regulation in TFKs. Over the last few
      years, a large number of genomes from various phyla have been sequenced making it
      possible to study evolutionary relationships at the molecular and sequence level.
      Using bioinformatics tools, we for the first time demonstrate that a TFK ancestor
      exists in the unicellular choanoflagellate Monosiga brevicollis, which is the
      closest known relative to metazoans with a sequenced genome. The analysis of the
      genomes for sponges, insects, hagfish, and frogs suggests that these species
      encode a single TFK. The insect form has a divergent and unique N-terminal
      region. Duplications generating the five members took place prior to the
      emergence of vertebrates. Fishes have two or three forms and the platypus,
      Ornithorhynchus anatinus, has four (lacks Txk). Thus, not all mammals have all
      five TFKs. The single identified TFK in frogs is an ortholog of Tec. Bmx seems to
      be unique to mammals and birds. SH3BP5 is a negative regulator of Btk. It is
      conserved in choanoflagellates and interestingly exists also in nematodes, which
      do not express TFKs, suggesting a broader function in addition to Btk regulation.
      The related SH3BP5-like protein is not found in Nematodes.

PMID- 19161833
TI  - Therapeutic approaches to ion channel diseases.
AB  - More than 400 genes are known that encode ion channel subunits. In addition,
      alternative splicing and heteromeric assembly of different subunits increase
      tremendously the variety of ion channels. Such many channels are needed to
      accomplish very complex cellular functions, whereas dysfunction of ion channels
      are key events in many pathological processes. The recent discovery of ion
      channelopathies, which, in its more stringent definition, encloses monogenic
      disorders due to mutations in ion channel genes, has largely contributed to our
      understanding of the function of the various channel subtypes and of the role of
      ion channels in multigenic or acquired diseases. Last but not least, ion channels
      are the main targets of many drugs already used in the clinics. Most of these
      drugs were introduced in therapy based on the experience acquired quite
      empirically, and many were discovered afterward to target ion channels. Now,
      intense research is being conducted to develop new drugs acting selectively on
      ion channel subtypes and aimed at the understanding of the intimate drug-channel
      interaction. In this review, we first focus on the pharmacotherapy of ion channel
      diseases, which includes many drugs targeting ion channels. Then, we describe the
      molecular pharmacology of ion channels, including the more recent advancement in
      drug development. Among the newest aspect of ion channel pharmacology, we draw
      attention to how polymorphisms or mutations in ion channel genes may modify
      sensitivity to drugs, opening the way toward the development of pharmacogenetics.

PMID- 19161831
TI  - Gene expression studies in mosquitoes.
AB  - Research on gene expression in mosquitoes is motivated by both basic and applied
      interests. Studies of genes involved in hematophagy, reproduction, olfaction, and
      immune responses reveal an exquisite confluence of biological adaptations that
      result in these highly-successful life forms. The requirement of female
      mosquitoes for a bloodmeal for propagation has been exploited by a wide diversity
      of viral, protozoan and metazoan pathogens as part of their life cycles.
      Identifying genes involved in host-seeking, blood feeding and digestion,
      reproduction, insecticide resistance and susceptibility/refractoriness to
      pathogen development is expected to provide the bases for the development of
      novel methods to control mosquito-borne diseases. Advances in mosquito
      transgenesis technologies, the availability of whole genome sequence information,
      mass sequencing and analyses of transcriptomes and RNAi techniques will assist
      development of these tools as well as deepen the understanding of the underlying
      genetic components for biological phenomena characteristic of these insect
      species.

PMID- 19161834
TI  - RNA turnover in prokaryotes, archaea and organelles. Preface.

PMID- 19161835
TI  - Analysis of RNA decay, processing, and polyadenylation in Escherichia coli and
      other prokaryotes.
AB  - This chapter provides detailed methodologies for isolating total RNA and
      polyadenylated RNA from E. coli and other prokaryotes, along with the procedures
      necessary to analyze the processing and decay of specific transcripts and
      determine their 3'- and 5'-ends. The RNA isolation methods described here
      facilitate isolating good-quality RNA in a very cost-effective way compared to
      the commercially available RNA isolation kits, without employing phenol and/or
      alcohol precipitation. We also discuss the limits associated with polyacrylamide
      and agarose gels for the separation of small and large RNAs. Methods useful for
      the analysis of post-transcriptionally modified transcripts and the processing of
      very large polycistronic transcripts are also presented.

PMID- 19161836
TI  - Analyzing the decay of stable RNAs in E. coli.
AB  - Stable RNA, mainly comprised of rRNA and tRNA, accounts for the majority of
      cellular RNA. Although normally stable under favorable growth conditions in the
      laboratory, these RNA species undergo extensive degradation responding to many
      environmental changes and stress conditions. Multiple ribonucleases and other
      enzymes may be involved in the decay of stable RNA. The onset and rate of
      degradation are probably determined by the status of the RNA as well as the
      availability of the degrading activities. The elucidation of pathways for stable
      RNA decay has been benefited by many biochemical and genetic approaches. These
      include purification of the enzymes and characterization of their substrate
      specificity in vitro, and studies of stable RNA decay by inactivating and
      overexpressing the degradation activities in vivo. Furthermore, RNA degradation
      intermediates have been characterized in detail, such as determining the sizes,
      the sequences, the 5'- and 3'-termini, etc. In this work, we describe the methods
      that are most commonly used in the study of the degradation and processing of
      stable RNA in E. coli. Most of them should be also useful in studies of other RNA
      species or RNA from other organisms.

PMID- 19161837
TI  - Genomic analysis of mRNA decay in E. coli with DNA microarrays.
AB  - The decay of mRNA plays an important role in the regulation of gene expression.
      Although relatively ignored for many years and regarded as a simple
      ribonucleotide salvage pathway, mRNA decay has been established in recent years
      as a well-defined cellular process that plays an integral role in determining
      gene expression. The recent application of microarray methods to the study of
      diverse organisms will help us to better understand these gene regulatory
      circuits and the influence of transcript stability on gene expression. DNA
      microarray technology is the method of choice to study individual mRNA half-lives
      on a global scale. It is important to standardize these methods to generate
      reproducible and reliable results. In this chapter, we describe experimental
      designs for the analysis of mRNA decay on a genome-wide scale and provide
      detailed protocols for each experimental step. We also present an analysis of the
      decay of chromosomally encoded mRNAs in E. coli.

PMID- 19161838
TI  - Co-immunopurification of multiprotein complexes containing RNA-degrading enzymes.
AB  - Co-immunopurification is a classical technique in which antiserum raised against
      a specific protein is used to purify a multiprotein complex. We describe work
      from our laboratory in which co-immunopurification was used to characterize the
      RNA degradosome of Escherichia coli, a multiprotein complex involved in RNA
      processing and mRNA degradation. Polyclonal rabbit antibodies raised against
      either RNase E or PNPase, two RNA degrading enzymes in the RNA degradosome, were
      used in co-immunopurification experiments aimed at studying the assembly of the
      RNA degradosome and mapping protein-protein interactions within the complex. In
      E. coli, this method has been largely supplanted by approaches in which proteins
      are engineered to contain tags that interact with commercially available
      antibodies. Nevertheless, we believe that the method described here is valid for
      the study of bacteria in which the genetic engineering needed to introduce tagged
      proteins is difficult or nonexistent. As an example, we briefly discuss ongoing
      work in our laboratory on the characterization of RNase E in the psychrotolerant
      bacterium Pseudoalteromonas haloplanktis.

PMID- 19161839
TI  - PABLO analysis of RNA: 5'-phosphorylation state and 5'-end mapping.
AB  - Recent studies have revealed that 5'-end-dependent RNA degradation in prokaryotes
      is triggered by pyrophosphate removal from the 5'-terminus to generate a
      monophosphorylated intermediate that is readily degraded. This chapter describes
      how to examine the 5'-phosphorylation state of any specific bacterial RNA by
      PABLO analysis. The method is based on the ability of monophosphorylated, but not
      triphosphorylated, RNA 5'-ends to undergo splinted ligation to a DNA
      oligonucleotide when juxtaposed by base pairing to a bridging oligonucleotide.
      PABLO analysis not only makes it possible to quantify the proportion of a
      particular RNA that is monophosphorylated in bacterial cells but also provides a
      more reliable method than primer extension for high-resolution mapping of RNA 5'
      termini.

PMID- 19161840
TI  - A proteomic approach to the analysis of RNA degradosome composition in
      Escherichia coli.
AB  - The RNA degradosome is a bacterial protein machine devoted to RNA degradation and
      processing. In Escherichia coli, it is typically composed of the endoribonuclease
      RNase E, which also serves as a scaffold for the other components: the
      exoribonuclease PNPase, the RNA helicase RhlB, and enolase. The variable presence
      of additional proteins, however, suggests that the degradosome is a flexible
      machine that may vary its composition in response to different conditions. Direct
      analysis of large protein complexes, together with simplified purification
      procedures, can facilitate qualitative and quantitative identification of RNA
      degradosome components under different physiologic and genetic conditions and can
      help to explain their role in the bacterial cell (see also Chapters 4, 11, 19, 20
      and 22 regarding methods for the studying the degradosome and other multiprotein
      complexes in this volume. Herewith we describe the application of
      multidimensional protein identification technology (MudPIT) in the rapid and
      quantitative identification of RNA degradosome components. RNA degradosome
      preparations obtained from specific conditions are enzymatically digested. The
      resulting peptides are fractionated using two-dimensional (ion-exchange and
      reversed-phase) chromatography and analyzed by tandem mass spectrometry.
      Bioinformatic analysis with the SEQUEST algorithm, which correlates
      experimentally obtained mass spectra with those predicted from peptide sequences
      in proteomic and translated genomic databases, allows identification of the
      corresponding proteins that compose the complex. The protein constituents of two
      or more degradosome samples are then compared to obtain a rapid evaluation of
      qualitative and quantitative differences in protein composition. Quantitative
      analysis is based on the observation that changes in relative protein abundance
      among different samples are reflected by statistical parameters (score values)
      assigned to each protein component of the RNA degradosome identified by the
      MudPIT approach. This correlation can be validated by independent methods such as
      Western blotting and determination of enzymatic activities. This fully automated
      procedure may be applied to the characterization of any complex protein mixture.

PMID- 19161841
TI  - New approaches to understanding double-stranded RNA processing by ribonuclease
      III purification and assays of homodimeric and heterodimeric forms of RNase III
      from bacterial extremophiles and mesophiles.
AB  - Ribonuclease III (RNase III) is a double-stranded (ds)-RNA-specific endonuclease
      that plays essential roles in the maturation and decay of coding and noncoding
      RNAs. Bacterial RNases III are structurally the simplest members of the RNase III
      family, which includes the eukaryotic orthologs Dicer and Drosha. High-resolution
      crystal structures of RNase III of the hyperthermophilic bacteria Aquifex
      aeolicus and Thermotoga maritima are available. A. aeolicus RNase III also has
      been cocrystallized with dsRNA or specific hairpin substrates. These structures
      have provided essential structural insight to the mechanism of dsRNA recognition
      and cleavage. However, comparatively little is known about the catalytic
      behaviors of A. aeolicus or T. maritima RNases III. This chapter provides
      protocols for the purification of A. aeolicus and T. maritima RNases III and also
      describes the preparation of artificial heterodimers of Escherichia coli RNase
      III, which are providing new insight on the subunit and domain interactions
      involved in dsRNA recognition and cleavage.

PMID- 19161842
TI  - Characterizing ribonucleases in vitro examples of synergies between biochemical
      and structural analysis.
AB  - The contribution of RNA degradation to the posttranscriptional control of gene
      expression confers on it a fundamental role in all biological processes.
      Ribonucleases (RNases) are essential enzymes that process and degrade RNA and
      constitute one of the main groups of factors that determine RNA levels in the
      cells. RNase II is a ubiquitous, highly processive hydrolytic exoribonuclease
      that plays an important role in RNA metabolism. This ribonuclease can act
      independently or as a component of the exosome, an essential RNA-degrading
      multiprotein complex. In this chapter, we explain the general procedures normally
      used for the characterization of ribonucleases, using as an example a study
      performed with Escherichia coli RNase II. We present the overexpression and
      purification of RNase II recombinant enzyme and of a large set of RNase II
      truncations. We also describe several methods that can be used for biochemically
      characterizing the exoribonucleolytic activity and studying RNA binding in vitro.
      Dissociation constants were determined by electrophoretic mobility shift assay
      (EMSA), surface plasmon resonance (SPR), and filter binding assays using
      different single- or double-stranded RNA substrates. We discuss the synergies
      among the biochemical analyses and the structural studies. These methods will be
      very useful for the study of other ribonucleases.

PMID- 19161843
TI  - The role of RNA chaperone Hfq in poly(A) metabolism methods to determine
      positions, abundance, and lengths of short oligo(A) tails.
AB  - Polyadenylation is a posttranscriptional modification of RNA occurring in
      prokaryotes, eukaryotes, and organelles. Long poly(A) tails help export
      eukaryotic mRNAs and promote mRNA stability and translation, whereas the short
      bacterial tails facilitate RNA decay. The scarcity of polyadenylated RNAs is one
      of the obstacles for investigators studying bacterial polyadenylation. The two
      methods described in this chapter were developed to determine how the poly(A)
      binding protein Hfq affects the polyadenylation of bacterial RNAs. The first is a
      3'-RACE protocol specific to oligoadenylated RNA. This method was designed to
      rapidly collect a large amount of poly(A) containing 3'-terminal sequences to
      perform statistical analysis. The second method is an RNA sizing protocol to
      analyze the polyadenylation status of primary transcripts that were not
      efficiently detected by 3'-RACE. The latter procedure is based on Northern blot
      analysis of 3'-RNA fragments generated by RNase H. In the presence of a gene
      specific methylated chimeric RNA-DNA oligonucleotide, the enzyme is directed to a
      unique cleavage site. The 3'-RNA fragments, differing by just one nucleotide at
      their 3'-ends, are then separated in polyacrylamide gels.

PMID- 19161844
TI  - Assaying DEAD-box RNA helicases and their role in mRNA degradation in Escherichia
      coli.
AB  - The DEAD-box RNA helicases are a ubiquitous family of enzymes involved in
      processes that include RNA splicing, ribosome biogenesis, and mRNA degradation.
      In general, these enzymes help to unwind short stretches of double-stranded RNA
      in processes that involve the remodeling of RNA structure or of ribonucleoprotein
      complexes. Here we describe work from our laboratory on the characterization of
      the RhlB of Escherichia coli, a DEAD-box RNA helicase that is part of a
      multienzyme complex known as the RNA degradosome. RhlB interacts physically and
      functionally with RNase E and polynucleotide phosphorylase (PNPase), two other
      components of the RNA degradosome. We describe enzyme assays that demonstrated
      that the interaction between RhlB and RNase E is necessary for the ATPase and RNA
      unwinding activities of RhlB. We also describe an mRNA degradation assay that
      showed that RhlB facilitates the degradation of structured mRNA by PNPase. These
      assays are discussed in the context of how they have contributed to our
      understanding of the function of RhlB in mRNA degradation.

PMID- 19161845
TI  - Preparation of the Escherichia coli RNase E protein and reconstitution of the RNA
      degradosome.
AB  - The RNA degradosome is a multienzyme complex that plays a key role in the
      processing of stable RNAs, the degradation of mRNAs, and the action of small
      regulatory RNAs. Initially discovered in Escherichia coli, similar or related
      complexes are found in other bacteria. The core of the RNA degradosome is the
      essential endoribonuclease, RNase E. The C-terminus of this enzyme serves as a
      scaffold to which other components of the RNA degradosome bind. These ligands
      include the phosphorolytic 3'-exonuclease, polynucleotide phosphorylase, the DEAD
      box RNA helicase, RhlB, and the glycolytic enzyme, enolase. In addition, the DEAD
      box RNA helicases CsdA and RhlE and the RNA binding protein, Hfq, may bind to
      RNase E in place of one or more of the prototypical components. This chapter
      describes purification of RNase E (the Rne protein), reconstitution of a minimal
      degradosome that recapitulates the activity of authentic degradosomes, and
      methods for the assay of the reconstituted complex.

PMID- 19161846
TI  - Identifying and characterizing substrates of the RNase E/G family of enzymes.
AB  - The study of RNA decay and processing in Escherichia coli has revealed a central
      role for RNase E, an endonuclease that is essential for cell viability. This
      enzyme is required for the normal rapid decay of many transcripts and is involved
      in the processing of precursors of 16S and 5S ribosomal RNA, transfer RNA, the
      transfer-messenger RNA, and the RNA component of RNase P. Although there is
      reasonable knowledge of the repertoire of transcripts cleaved by RNase E in E.
      coli, a detailed understanding of the molecular recognition events that control
      the cleavage of RNA by this key enzyme is only starting to emerge. Here we
      describe methods for identifying sites of endonucleolytic cleavage and
      determining whether they depend on functional RNase E. This is illustrated with
      the pyrG eno bicistronic transcript, which is cleaved in the intergenic region
      primarily by an RNase E-dependent activity and not as previously thought by RNase
      III. We also describe the use of oligoribonucleotide and in vitro-transcribed
      substrates to investigate cis-acting factors such as 5'-monophosphorylation,
      which can significantly enhance the rate of cleavage but is insufficient to
      ensure processivity. Most of the approaches that we describe can be applied to
      the study of homologs of E. coli RNase E, which have been found in approximately
      half of the eubacteria that have been sequenced.

PMID- 19161847
TI  - Construction and characterization of E. coli K12 strains in which the
      transcription of selected genes is desynchronized from translation.
AB  - In Escherichia coli, synthesis and translation of individual mRNAs are usually
      synchronous, so that no long ribosome-free mRNA stretch exists between the RNA
      polymerase and the leading ribosome. By comparing situations in which the same
      mRNA (the lacZ mRNA) is synthesized either by the genuine E. coli RNA polymerase
      or the faster T7 RNA polymerase, we have previously shown that the outpacing of
      ribosomes by RNA polymerase destabilizes mRNAs, and more so as outpacing becomes
      larger. This destabilization requires the noncatalytic C-terminal region of RNase
      E; more generally, there is circumstantial evidence that this region is
      specifically involved in the fast decay of various untranslated mRNAs. The
      genetic system designed for desynchronizing transcription and translation with T7
      RNA polymerase was originally designed in the E. coli B strain BL21(DE3). Here,
      we describe procedures for transferring this system to the more common E. coli
      K12 background. We also show that it can be used as a screen for identifying
      factors involved in the instability of untranslated mRNA. Protocols in use in
      this laboratory for RNA extraction, Northern blotting, and beta-galactosidase
      assay are described and critically discussed.

PMID- 19161848
TI  - Analysis of mRNA decay in Bacillus subtilis.
AB  - Studies of mRNA turnover in B. subtilis are less well known than in E. coli. Here
      we provide researchers who have an interest in gram-positive RNA processing with
      several protocols for RNA isolation, for 5'- and 3'-mapping of mRNAs and mRNA
      decay fragments, and we also include a comprehensive listing of B. subtilis
      mutants that are deficient in ribonucleases thought to be involved in mRNA decay.

PMID- 19161849
TI  - Assay of Bacillus subtilis ribonucleases in vitro.
AB  - Significant progress has been made recently regarding the identification of the
      ribonucleases involved in RNA maturation and degradation in Bacillus subtilis.
      More than half of these enzymes have no ortholog in Escherichia coli. To confirm
      that the in vivo effects of mutations in genes encoding RNases are direct, it is
      often necessary to purify the enzymes and assay their activity in vitro.
      Development of such assays is also necessary for detailed biochemical analysis of
      enzyme properties. In this chapter, we describe the purification and assay of 12
      RNases of B. subtilis thought to be involved in stable RNA maturation or RNA
      degradation.

PMID- 19161850
TI  - Staphylococcus aureus endoribonuclease III purification and properties.
AB  - Staphylococcus aureus ribonuclease III (Sa-RNase III) belongs to the enzyme
      family known to process double-stranded RNAs consisting of two turns of the RNA
      helix. Although the enzyme is thought to play a role in ribosomal RNA processing
      and gene regulation, the deletion of the rnc gene in S. aureus does not affect
      cell growth in rich medium. S. aureus RNase III acts in concert with regulatory
      RNAIII to repress the expression of several mRNAs encoding virulence factors. The
      action of the RNase is most likely to initiate the degradation of repressed mRNAs
      leading to an irreversible repression. In this chapter, we describe the
      overexpression and purification of recombinant RNase III from S. aureus, and we
      show that its biochemical properties are similar to the orthologous enzyme from
      Escherichia coli. Both enzymes similarly recognize and cleave different RNA
      substrates and RNA-mRNA duplexes.

PMID- 19161851
TI  - Studying tmRNA-mediated surveillance and nonstop mRNA decay.
AB  - In bacteria, ribosomes stalled at the 3'-end of nonstop or defective mRNAs are
      rescued by the action of a specialized ribonucleoprotein complex composed of
      tmRNA and SmpB protein in a process known as trans-translation; for recent
      reviews see Dulebohn et al. [2007], Keiler [2007], and Moore and Sauer [2007].
      tmRNA is a bifunctional RNA that acts as both a tRNA and an mRNA. SmpB-bound
      tmRNA is charged with alanine by alanyl-tRNA synthetase and recognized by EF-Tu
      (GTP). The quaternary complex of tmRNA-SmpB-EF-Tu and GTP recognizes stalled
      ribosomes and transfers the nascent polypeptide to the tRNA-like domain of tmRNA.
      A specialized reading frame within tmRNA is then engaged as a surrogate mRNA to
      append a 10 amino acid (ANDENYALAA) tag to the C-terminus of the nascent
      polypeptide. A stop codon at the end of the tmRNA reading frame then facilitates
      normal termination and recycling of the translation machinery. Through this
      surveillance mechanism, stalled ribosomes are rescued, and nascent polypeptides
      bearing the C-terminal tmRNA-tag are directed for proteolysis. Several proteases
      (ClpXP, ClpAP, Lon, FtsH, and Tsp) are known to be involved in the degradation of
      tmRNA-tagged proteins (Choy et al., 2007; Farrell et al., 2005; Gottesman et al.,
      1998; Herman et al., 1998, 2003; Keiler et al., 1996). In addition to its
      ribosome rescue and peptide tagging activities, trans-translation also
      facilitates the selective decay of nonstop mRNAs in a process that is dependent
      on the activities of SmpB protein, tmRNA, and the 3' to 5'-exonuclease, RNase R
      (Mehta et al., 2006; Richards et al., 2006; Yamamoto et al., 2003). Here, we
      describe methods and strategies for the purification of tmRNA, SmpB, Lon, and
      RNase R from Escherichia coli that are likely to be applicable to other bacterial
      species. Protocols for the purification of the Clp proteases, Tsp, and FtsH, as
      well as EF-Tu and other essential E. coli translation factors may be found
      elsewhere (Joshi et al., 2003; Kihara et al., 1996; Makino et al., 1999; Maurizi
      et al., 1990; Shotland et al., 2000). In addition, we present biochemical and
      genetic assays to study the various aspects of the trans-translation mechanism.

PMID- 19161852
TI  - Analyses of mRNA destabilization and translational inhibition mediated by Hfq
      binding small RNAs.
AB  - A major class of bacterial small RNAs binds to an RNA chaperone Hfq and acts via
      imperfect base pairing to regulate the translation and stability of target mRNAs
      under specific physiological conditions. SgrS, an example for this class of small
      RNAs, is induced in response to the accumulation of glucose phosphates and
      downregulates the ptsG mRNA, which encodes the glucose transporter IICB(Glc) in
      Escherichia coli. SgrS forms a specific ribonucleoprotein complex with RNase E
      through Hfq. The regulatory outcomes of SgrS are the inhibition of translation
      and RNase E-dependent degradation of ptsG mRNA. Translational inhibition is the
      primary event for gene silencing. The crucial base pairs for the action of SgrS
      are confined to the 6-nt region overlapping the Shine-Dalgarno sequence of the
      target mRNA. Hfq accelerates the rate of duplex formation between SgrS and the
      target mRNA. Membrane localization of the target mRNA contributes to efficient
      SgrS action by competing with ribosome loading. Here, we describe major
      experimental methods and results used to study functions of Hfq-binding small
      RNAs in our laboratory. These are illustrated using the regulation of ptsG mRNA
      by SgrS is used as an example.

PMID- 19161853
TI  - In vivo and in vitro studies of RNA degrading activities in Archaea.
AB  - Controlled degradation of RNA is important for the regulation of gene expression
      in Bacteria and Eukarya, but information about these processes is limited in the
      domain of Archaea. To address this, we studied the half-life of different mRNAs
      in halophilic Archaea after blocking transcription with actinomycin D. We found
      that the stability of mRNAs of the gvp operons in Haloferax mediterranei varies
      under different growth conditions. To understand regulated mRNA decay in Archaea,
      we need to identify stability determinants within mRNAs and proteins, mainly
      ribonucleases (RNases), which recognize these determinants. First, we wanted to
      identify archaeal RNases independently of their sequence similarity to known
      RNases from Bacteria and Eukarya. To this end we performed fractionation of
      proteins from Halobacterium salinarum and tested the fractions for RNase activity
      with an internally labeled in vitro-synthesized mRNA. After three purification
      steps, we isolated an endoribonucleolytically active protein with similarities to
      the eukaryotic initiation factor 5A. Further characterization was performed with
      recombinant halobacterial IF-5A, which was purified from H. salinarum or
      Escherichia coli. Mutational analysis confirmed unambiguously its RNase activity.
      In another study, we aimed to purify a double-strand-specific endoribonuclease
      from Sulfolobus solfataricus. Seven purification steps led to the isolation of
      two different dehydrogenases with RNase properties. Interestingly, their RNase
      activity resembled that of aIF-5A and of highly diluted RNase A. RNA was cleaved
      preferentially between C and A nucleotides in single-stranded regions, and the
      activity was inhibited at MgCl(2) concentrations >5 mM and at KCl concentrations
      >200 mM. However, it was possible to distinguish the activity of the archaeal
      proteins from the activity of RNase A. In a different approach, we used a
      bioinformatics prediction of the archaeal exosome to purify this protein complex
      from S. solfataricus. Isolation by coimmunoprecipitation revealed the presence of
      four orthologs of eukaryotic exosomal subunits and at least one archaea-specific
      subunit. We characterized the S. solfataricus exosome as a major enzyme involved
      in phosphorolytic RNA degradation and in RNA polyadenylation. Here we describe in
      detail the techniques used to achieve these results.

PMID- 19161854
TI  - Expression, reconstitution, and structure of an archaeal RNA degrading exosome.
AB  - The exosome is a protein complex that participates in a wide variety of RNA
      processing, degradation, and quality-control pathways. The exosome is conserved
      in all eukaryotes studied to date and is also present in many archaeal organisms,
      albeit in a simpler form. To gain insights into the architecture of the exosome
      complex, we have chosen the hyperthermophilic archaeum Sulfolobus solfataricus as
      a model system. Here we describe the coexpression, purification, and crystal
      structure determination of archaeal exosome complexes. To understand how the
      archaeal exosome binds and degrades RNA, we designed RNA substrates for
      degradation experiments exploiting the knowledge of the geometric constraints of
      the exosome structure. Furthermore, we describe several crystal structures in
      which RNA substrates were diffused into crystals and how anomalous scattering
      from 5-iodo-uridine-modified RNA was used to locate low-occupancy RNA binding
      sites.

PMID- 19161855
TI  - Polyadenylation-mediated RNA degradation in plant mitochondria.
AB  - In plant mitochondria, polyadenylation-mediated RNA degradation is involved in
      several key aspects of genome expression, including RNA maturation, RNA turnover,
      and RNA surveillance. We describe here a combination of in vivo, in vitro, and in
      organello methods that have been developed or optimized to characterize this RNA
      degradation pathway. These approaches include several PCR-based methods designed
      to identify polyadenylated RNA substrates, as well as in vitro and in organello
      systems, to study functional aspects of the RNA degradation processes. Taken
      together, identification of RNA substrates combined with information from
      degradation assays are invaluable tools to dissect the mechanisms and roles of
      RNA degradation in plant mitochondrial genome expression.

PMID- 19161856
TI  - In vivo and in vitro approaches for studying the yeast mitochondrial RNA
      degradosome complex.
AB  - The mitochondrial degradosome (mtEXO) of S. cerevisiae is the main
      exoribonuclease of yeast mitochondria. It is involved in many pathways of
      mitochondrial RNA metabolism, including RNA degradation, surveillance, and
      processing, and its activity is essential for mitochondrial gene function. The
      mitochondrial degradosome is a very simple example of a 3' to 5'
      exoribonucleolytic complex. It is composed of only two subunits: Dss1p, which is
      an RNR (RNase II-like) family exoribonuclease, and Suv3p, which is a DExH/D-box
      RNA helicase. The two subunits form a tight complex and their activities are
      highly interdependent, with the RNase activity greatly enhanced in the presence
      of the helicase subunit, and the helicase activity entirely dependent on the
      presence of the ribonuclease subunit. In this chapter, we present methods for
      studying the function of the yeast mitochondrial degradosome in vivo, through the
      analysis of degradosome-deficient mutant yeast strains, and in vitro, through
      heterologous expression in E. coli and purification of the degradosome subunits
      and reconstitution of a functional complex. We provide the protocols for studying
      ribonuclease, ATPase, and helicase activities and for measuring the RNA binding
      capacity of the complex and its subunits.

PMID- 19161857
TI  - Measuring mRNA decay in human mitochondria.
AB  - Human mitochondria contain a genome encoding 13 proteins, all of which are
      components of respiratory chain complexes. Mutations in human mitochondrial DNA
      often have pathological consequences. Although 12 of the mitochondrial mRNAs are
      generated from the same polycistronic transcript, the steady-state level of each
      mRNA differs. The stability of each mitochondrial mRNA is post-transcriptionally
      controlled by polyadenylation and deadenylation. However, the molecular mechanism
      by which each mRNA attains a unique stability is not fully understood. In this
      report, we describe a practical method for measuring the half-lives of human
      mitochondrial mRNAs using quantitative real-time reverse transcription PCR.

PMID- 19161858
TI  - Detection and characterization of polyadenylated RNA in Eukarya, Bacteria,
      Archaea, and organelles.
AB  - The posttranscriptional addition of poly(A) extensions to RNA is a phenomenon
      common to almost all organisms. In eukaryotes, a stable poly(A) tail is added to
      the 3'-end of most nucleus-encoded mRNAs, as well as to mitochondrion-encoded
      transcripts in animal cells. In prokaryotes and organelles, RNA molecules are
      polyadenylated as part of a polyadenylation-stimulated RNA degradation pathway.
      In addition, polyadenylation of nucleus-encoded transcripts in yeast and human
      cells was recently reported to promote RNA degradation. Not only homopolymeric
      poly(A) tails, composed exclusively of adenosines, but also heteropolymeric
      poly(A)-rich extensions, which include the other three nucleotides as well, have
      been observed in bacteria, archaea, chloroplasts, and human cells. In most
      instances, the detection of nonabundant truncated transcripts with
      posttranscriptionally added poly(A) or poly(A)-rich extensions serves as a
      telltale sign of the presence of a polyadenylation-stimulated RNA degradation
      pathway. In this chapter, we describe several methods found to be efficient in
      detecting and characterizing polyadenylated transcripts in bacteria, archaea,
      organelles, and nucleus-encoded RNAs. Detailed protocols for the oligo(dT)- and
      circularized reverse transcription (cRT) PCR methods, as well as the ribonuclease
      digestion method, are outlined, along with examples of results obtained with
      these techniques.

PMID- 19161859
TI  - RNA decay by messenger RNA interferases.
AB  - Two abundant toxin-antitoxin (TA) gene families, relBE and mazEF, encode mRNA
      cleaving enzymes whose ectopic overexpression abruptly inhibits translation and
      thereby induces a bacteriostatic condition. Here we describe and discuss
      protocols for the overproduction, purification, and analysis of mRNA cleaving
      enzymes such as RelE of Escherichia coli and the corresponding antitoxin RelB. In
      particular, we describe a set of plasmid vectors useful for the detailed analysis
      of cleavage sites in model mRNAs.

PMID- 19161860
TI  - Current controversies in perinatology. Preface.

PMID- 19161861
TI  - Strategies to prevent bacterial and fungal infection in the neonatal intensive
      care unit.
AB  - Hospital-acquired infections are one of the leading causes of preventable
      morbidity and mortality in neonatal intensive care units (NICUs). Device-related
      infections, such as catheter-associated blood stream infections (CABSIs) and
      ventilator-associated pneumonia (VAP), are the most common nosocomial infections.
      This review examines the pathogenesis of CABSIs and methods, widely accepted and
      novel, that can be used to help prevent them. Strategies to prevent fungal
      infections, which are often associated with the presence of a central venous
      catheter, are also reviewed. Finally, the dilemmas in the diagnosis and
      prevention of VAP in the NICU are discussed.

PMID- 19161863
TI  - Iron therapy for preterm infants.
AB  - Preterm infants are at risk for both iron deficiency and iron overload. The role
      of iron in multiple organ functions suggests that iron supplementation is
      essential for the preterm infant. Conversely, the potential for iron overload and
      the poorly developed antioxidant measures in the preterm infant argue against
      indiscriminate iron supplementation in this population. This article reviews the
      predisposing factors and consequences of iron deficiency and iron overload in the
      preterm infant, discusses the current recommendation for iron supplementation and
      its appropriateness, and describes potential management strategies that strike a
      balance between iron deficiency and iron toxicity.

PMID- 19161862
TI  - Drugs of choice for sedation and analgesia in the neonatal ICU.
AB  - Painful procedures in the neonatal ICU are common, undertreated, and lead to
      adverse consequences. The drugs most commonly used to treat neonatal pain include
      the opiates, benzodiazepines, barbiturates, ketamine, propofol, acetaminophen,
      and local and topical anesthetics. This article discusses the indications for and
      advantages and disadvantages of the commonly used analgesic drugs. Guidance and
      references for drugs and dosing for specific neonatal procedures are provided.

PMID- 19161864
TI  - Inhaled nitric oxide for preterm neonates.
AB  - The evidence for the benefits of inhaled nitric oxide (iNO) on gas exchange,
      cytokine-induced lung inflammation, and vascular dysfunction has been
      demonstrated by several animal and human studies. The use of iNO in extremely low
      birth weight neonates for the prevention of adverse outcomes like chronic lung
      disease and neurologic injury has been investigated, but the findings remain
      inconclusive. This review briefly outlines the biologic rationale for the use of
      iNO in preterm neonates and the results on the outcome measures of
      bronchopulmonary dysplasia and brain injury from the recent clinical trials. This
      article focuses on the potential toxicities, persistent controversies, and
      unanswered questions regarding the use of this treatment modality in this patient
      population at high risk for adverse outcomes.

PMID- 19161865
TI  - Racial disparity in low birth weight and infant mortality.
AB  - In the United States, African-American infants have significantly worse outcomes
      than white infants. In this review, the authors look beyond traditional risk
      factors and explore the social context of race in this country in an effort to
      understand African-American women's long-standing pregnancy outcome disadvantage.
      In the process, new insights are highlighted concerning likely causes for the
      poor birth outcomes of white infants in this country compared with infants in
      most other industrialized nations.

PMID- 19161866
TI  - Evaluation and treatment of hypotension in the preterm infant.
AB  - A large proportion of very preterm infants receive treatment for hypotension. The
      definition of hypotension is unclear, and, currently, there is no evidence that
      treating it improves outcomes or, indeed, which treatment to choose among the
      available alternatives. Assessment of circulatory adequacy of the preterm infant
      requires a careful clinical assessment and may also require ancillary
      investigations. The most commonly used interventions, fluid boluses and dopamine,
      are problematic: fluid boluses are statistically associated with worse clinical
      outcomes and may not even increase blood pressure, whereas dopamine increases
      blood pressure mostly by causing vasoconstriction and may decrease perfusion. For
      neither intervention is there any reliable data showing clinical benefit.
      Prospective trials of intervention for hypotension and circulatory compromise are
      urgently required.

PMID- 19161867
TI  - Indications for home apnea monitoring (or not).
AB  - Although there is a large body of literature describing infants who experience
      apnea of prematurity and apparent life-threatening events, there is no consensus
      regarding the use of home monitoring. This article focuses on issues that affect
      decision making regarding the use of home monitors in these two groups of infants
      and reviews existing data to guide a decision to discontinue monitoring at
      hospital discharge or to prescribe monitoring in the home.

PMID- 19161868
TI  - Short bowel syndrome: how short is too short?
AB  - Short bowel syndrome (SBS) is the most common cause of intestinal failure. This
      article discusses the prognostic factors that predict weaning from parenteral
      nutrition in SBS. The article also delineates an approach to enteral feeding in
      SBS.

PMID- 19161870
TI  - Evaluation and management of stroke in the neonate.
AB  - Ischemic perinatal stroke (IPS) occurs in 1 of 2300 to 5000 live births. It is an
      under-recognized cause of significant long-term disabilities, including
      hemiplegic cerebral palsy, epilepsy, cognitive delays, and behavioral
      impairments. The pathophysiology is complex and multifactorial, involving
      maternal, fetal, placental, and neonatal factors. Knowledge and interventions are
      emerging to facilitate early diagnosis and treatment of IPS. Early treatment may
      translate into improved long-term neurodevelopmental outcomes.

PMID- 19161869
TI  - Anemia in the preterm infant: erythropoietin versus erythrocyte transfusion--it's
      not that simple.
AB  - Since the late 1980s recombinant human erythropoietin (r-EPO) has been studied as
      an alternative to packed red blood cell (RBC) transfusion for the treatment of
      anemia of prematurity in very low birth weight infants. Initial trials and
      reports focused on r-EPO's ability to prevent or treat anemia of prematurity with
      the goal of eliminating RBC transfusion but achieved limited success. New
      concerns about the safety of r-EPO administration have emerged. Past cost-benefit
      analyses of r-EPO administration versus transfusion for the treatment of anemia
      of prematurity have been nearly balanced. Autologous transfusion, blood-sparing
      technologies, changes in RBC transfusion technique and safety, and further
      elucidation of the risk-benefit ratio of r-EPO therapy may change the cost
      benefit analysis.

PMID- 19161871
TI  - Screening for maternal depression in the neonatal ICU.
AB  - Postpartum depression is common in women with infants in the neonatal ICU.
      Maternal depression can affect infant health and development adversely. A
      screening program for depression in the neonatal ICU could identify women who
      have depressive symptoms and facilitate their referral for follow-up services.

PMID- 19161872
TI  - Controversies in the treatment of gastroesophageal reflux disease in preterm
      infants.
AB  - Gastroesophageal reflux (GER) is common in preterm infants and usually is a
      physiologic phenomenon with little clinical consequence. GER resulting in
      clinical signs and symptoms is considered pathologic gastroesophageal reflux
      disease (GERD). Correlation of clinical signs and symptoms with GER has been poor
      in most studies. The efficacy of GERD therapy has not been studied systematically
      in preterm infants. Furthermore, GERD therapy, particularly with prokinetic
      agents and surgery, carries potential risks that must be considered before
      initiation of therapy. Alternative diagnoses, pretreatment diagnostic testing,
      and desired treatment outcomes should be considered before initiating GERD
      therapy. Cessation of empiric GERD therapy should be considered, particularly if
      treatment does not result in the desired clinical outcome.

PMID- 19161873
TI  - Optimizing growth in the preterm infant.
AB  - Most very low birth weight preterm infants experience postnatal growth failure in
      the neonatal ICU. In an attempt to minimize this phenomenon, the nutritional
      support of these infants has tended to become more aggressive in recent years and
      has become a focus of much study. Despite this attention, many questions remain
      unresolved. This article examines several of these issues, including the
      controversies regarding optimal postnatal growth velocity, early aggressive
      nutritional support, and the transition to enteral nutrition in preterm infants.

PMID- 19161874
TI  - Postnatal corticosteroids for bronchopulmonary dysplasia.
AB  - Corticosteroids are used to improve lung function in infants who are progressing
      toward bronchopulmonary dysplasia. Corticosteroids facilitate extubation, but
      there is conflicting information about adverse effects on the developing brain.
      An approach to minimizing risk is to use low-dose, short-duration treatments in
      the highest risk ventilator-dependent patients. Questions remain about which
      corticosteroid is the safest and how to dose that corticosteroid.

PMID- 19161875
TI  - The role of genomics in the neonatal ICU.
AB  - Results of both the Human Genome and International HapMap Projects have provided
      the technology and resources necessary to enable fundamental advances through the
      study of DNA sequence variation in almost all fields of medicine, including
      neonatology. Genome-wide association studies are now practical, and the first of
      these studies are appearing in the literature. This article provides the reader
      with an overview of the issues in technology and study design relating to genome
      wide association studies and summarizes the current state of association studies
      in neonatal ICU populations with a brief review of the relevant literature.
      Future recommendations for genomic association studies in neonatal ICU
      populations are also provided.

PMID- 19161877
TI  - Promise of blood- and bone marrow-derived stem cell transplantation for
      functional cardiac repair: putting it in perspective with existing therapy.
AB  - Intracoronary transplantation of peripheral blood- or bone marrow-derived cells,
      as tested in several recent trials, is associated with moderate increases in left
      ventricular (LV) ejection fraction (EF) and a small reduction of LV end-systolic
      volumes. Substantial variability exists between trials, and most of them are
      based on a small number of patients. Meta-analyses estimated an increase in EF of
      3% to 4% more in comparison with control patients. In this review, the effects
      are put into perspective with established treatment options for acute myocardial
      infarction (AMI), such as thrombolysis and acute percutaneous interventions or
      pharmacotherapy aimed at favorably influencing the cardiac remodeling process.
      Changes in functional and morphometric parameters of LV performance after cell
      therapy appear to be in the range of effects observed with reperfusion therapy,
      pharmacotherapeutic interventions influencing the renin-angiotensin-aldosterone
      pathway, and beta-blockers after AMI.

PMID- 19161878
TI  - Thrombus aspiration during primary percutaneous coronary intervention improves
      myocardial reperfusion and reduces infarct size: the EXPIRA (thrombectomy with
      export catheter in infarct-related artery during primary percutaneous coronary
      intervention) prospective, randomized trial.
AB  - OBJECTIVES: The purpose of this study was to evaluate the impact on myocardial
      perfusion and infarct size as assessed by contrast-enhanced magnetic resonance
      imaging (CE-MRI) of a manual thrombectomy device, Export Medtronic (EM)
      (Medtronic Inc., Minneapolis, Minnesota), as adjunctive therapy in primary
      percutaneous coronary intervention (PPCI) in a subset of patients with anterior
      ST-segment elevation myocardial infarction (STEMI). BACKGROUND: PPCI may cause
      thrombus dislodgment, leading to microvascular damage. METHODS: One hundred
      seventy-five STEMI patients were randomly assigned to standard percutaneous
      coronary intervention (PCI) (n = 87) or EM-PCI (n = 88). The primary end points
      were the occurrence of myocardial blush grade > or =2 and the rate of 90-min ST
      segment resolution >70%. The CE-MRI substudy was performed in 75 patients with
      anterior STEMI to assess microvascular obstruction and infarct size. RESULTS:
      Myocardial blush grade > or =2 and ST-segment resolution occurred more frequently
      in the EM-PCI group (88% vs. 60%, p = 0.001; and 64% vs. 39%, p = 0.001). In the
      acute phase, microvascular obstruction extent was significantly lower in the EM
      PCI group and at 3 months, infarct size was significantly reduced only in the EM
      PCI group. A lower incidence of cardiac death in the EM-PCI group (4.6% vs. 0%,
      log-rank test p = 0.02) was observed at 9 months. CONCLUSIONS: Thrombectomy
      prevents thrombus embolization and preserves microvascular integrity reducing
      infarct size, and it therefore represents an useful adjunctive therapy in PPCI.

PMID- 19161879
TI  - Meta-analysis of the relationship between non-high-density lipoprotein
      cholesterol reduction and coronary heart disease risk.
AB  - OBJECTIVES: To determine the relationship between non-high-density lipoprotein
      cholesterol (HDL-C) lowering and coronary heart disease (CHD) risk reduction for
      various lipid-modifying therapies. BACKGROUND: Non-HDL-C is the second lipid
      target of therapy after low-density lipoprotein cholesterol (LDL-C). METHODS:
      Randomized placebo or active-controlled trials were evaluated. The effect of mean
      non-HDL-C reduction on the relative risk of nonfatal myocardial infarction and
      CHD death was estimated using Bayesian random-effects meta-analysis models
      adjusted for study duration. Cochrane's Q was used to test for heterogeneity.
      RESULTS: Inclusion criteria were met by 14 statin (n = 100,827), 7 fibrate (n =
      21,647), and 6 niacin (n = 4,445) trials, and 1 trial each of a bile acid
      sequestrant (n = 3,806), diet (n = 458), and ileal bypass surgery (n = 838). For
      statins, each 1% decrease in non-HDL-C resulted in an estimated 4.5-year CHD
      relative risk of 0.99 (95% Bayesian confidence interval: 0.98 to 1.00). The
      fibrate model did not differ from the statin model (Bayes factor K = 0.49) with
      no evidence of heterogeneity. The niacin model was moderately different from the
      statin model (K = 7.43), with heterogeneity among the trials (Q = 11.8, 5 df; p =
      0.038). The only niacin monotherapy trial (n = 3,908) had a 1:1 relationship
      between non-HDL-C and risk reduction. No consistent relationships were apparent
      for the 5 small trials of niacin in combination. The 95% confidence intervals for
      the single trials of diet, bile acid sequestrants, and surgery also included the
      1:1 relationship. CONCLUSIONS: Non-HDL-C is an important target of therapy for
      CHD prevention. Most lipid-modifying drugs used as monotherapy have an
      approximately 1:1 relationship between percent non-HDL-C lowering and CHD
      reduction.

PMID- 19161880
TI  - Persistent impairment of endothelial vasomotor function has a negative impact on
      outcome in patients with coronary artery disease.
AB  - OBJECTIVES: We assessed the hypothesis that changes in endothelial vasomotor
      function in response to optimized therapy for atherosclerotic coronary artery
      disease predict future cardiovascular events. BACKGROUND: Although endothelial
      vasomotor dysfunction is a predictor of cardiovascular events, it remains unclear
      whether reversibility of endothelial dysfunction in response to risk factor
      reduction provides prognostic information. METHODS: This study included 251
      patients with newly diagnosed coronary artery disease and an impaired flow
      mediated dilation (FMD) of the brachial artery (FMD <5.5%). Measurement of FMD
      was repeated after 6 months for individualized and optimized therapy to reduce
      risk factors according to American College of Cardiology/American Heart
      Association guidelines. Patients were followed up for 36 months or until 1 of the
      following events occurred: cardiac death, nonfatal myocardial infarction,
      recurrent and refractory angina pectoris requiring coronary revascularization, or
      ischemic stroke. RESULTS: FMD was persistently impaired (<5.5%) in 104 (41%)
      patients after 6 months of optimized therapy, whereas it improved (FMD > or
      =5.5%) in the remaining 147 (59%) patients. During 36 months of follow-up, events
      occurred in 27 (26%) patients with persistently impaired FMD and in 15 (10%)
      patients with improved FMD (p < 0.01 by chi-square test). Multivariate Cox
      hazards analysis showed that persistent impairment of FMD was an independent
      predictor of events (hazard ratio: 2.9, 95% confidence interval: 1.5 to 6.2, p <
      0.01). Baseline FMD before the optimized therapy to reduce risk factor had no
      significant prognostic information. CONCLUSIONS: Persistent impairment of
      endothelial vasomotor function despite optimized therapy to reduce risk factors
      has an adverse impact on outcome in coronary artery disease patients.

PMID- 19161881
TI  - Individualized approach to the management of coronary heart disease: identifying
      the nonresponders before it is too late.

PMID- 19161882
TI  - Utility of the Seattle Heart Failure Model in patients with advanced heart
      failure.
AB  - OBJECTIVES: The aim of this study was to validate the Seattle Heart Failure Model
      (SHFM) in patients with advanced heart failure (HF). BACKGROUND: The SHFM was
      developed primarily from clinical trial databases and extrapolated the benefit of
      interventions from published data. METHODS: We evaluated the discrimination and
      calibration of SHFM in 445 advanced HF patients (age 52 +/- 12 years, 68.5% male,
      52.4% white, ejection fraction 18 +/- 8%) referred for cardiac transplantation.
      The primary end point was death (n = 92), urgent transplantation (n = 14), or
      left ventricular assist device (LVAD) implantation (n = 3); a secondary analysis
      was performed on mortality alone. RESULTS: Patients were receiving optimal
      therapy (angiotensin-II modulation 92.8%, beta-blockers 91.5%, aldosterone
      antagonists 46.3%), and 71.0% had an implantable device (defibrillator 30.4%,
      biventricular pacemaker 3.4%, combined 37.3%). During a median follow-up of 21
      months, 109 patients (24.5%) had an event. Although discrimination was adequate
      (c-statistic >0.7), the SHFM overall underestimated absolute risk (observed vs.
      predicted event rate: 11.0% vs. 9.2%, 21.0% vs. 16.6%, and 27.9% vs. 22.8% at 1,
      2, and 3 years, respectively). Risk underprediction was more prominent in
      patients with an implantable device. The SHFM had different calibration
      properties in white versus black patients, leading to net underestimation of
      absolute risk in blacks. Race-specific recalibration improved the accuracy of
      predictions. When analysis was restricted to mortality, the SHFM exhibited better
      performance. CONCLUSIONS: In patients with advanced HF, the SHFM offers adequate
      discrimination, but absolute risk is underestimated, especially in blacks and in
      patients with devices. This is more prominent when including transplantation and
      LVAD implantation as an end point.

PMID- 19161883
TI  - Prognostic indicators: useful for clinical care?

PMID- 19161885
TI  - Are you as old as your arteries or as old as your coronary artery calcification
      score?

PMID- 19161884
TI  - Coronary calcium predicts events better with absolute calcium scores than age-sex
      race/ethnicity percentiles: MESA (Multi-Ethnic Study of Atherosclerosis).
AB  - OBJECTIVES: In this study, we aimed to establish whether age-sex-specific
      percentiles of coronary artery calcium (CAC) predict cardiovascular outcomes
      better than the actual (absolute) CAC score. BACKGROUND: The presence and extent
      of CAC correlates with the overall magnitude of coronary atherosclerotic plaque
      burden and with the development of subsequent coronary events. METHODS: MESA
      (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort study of 6,814
      asymptomatic participants followed for coronary heart disease (CHD) events
      including myocardial infarction, angina, resuscitated cardiac arrest, or CHD
      death. Time to incident CHD was modeled with Cox regression, and we compared
      models with percentiles based on age, sex, and/or race/ethnicity to categories
      commonly used (0, 1 to 100, 101 to 400, 400+ Agatston units). RESULTS: There were
      163 (2.4%) incident CHD events (median follow-up 3.75 years). Expressing CAC in
      terms of age- and sex-specific percentiles had significantly lower area under the
      receiver-operating characteristic curve (AUC) than when using absolute scores
      (women: AUC 0.73 versus 0.76, p = 0.044; men: AUC 0.73 versus 0.77, p < 0.001).
      Akaike's information criterion indicated better model fit with the overall score.
      Both methods robustly predicted events (>90th percentile associated with a hazard
      ratio [HR] of 16.4, 95% confidence interval [CI]: 9.30 to 28.9, and score >400
      associated with HR of 20.6, 95% CI: 11.8 to 36.0). Within groups based on age-,
      sex-, and race/ethnicity-specific percentiles there remains a clear trend of
      increasing risk across levels of the absolute CAC groups. In contrast, once
      absolute CAC category is fixed, there is no increasing trend across levels of age
      , sex-, and race/ethnicity-specific categories. Patients with low absolute scores
      are low-risk, regardless of age-, sex-, and race/ethnicity-specific percentile
      rank. Persons with an absolute CAC score of >400 are high risk, regardless of
      percentile rank. CONCLUSIONS: Using absolute CAC in standard groups performed
      better than age-, sex-, and race/ethnicity-specific percentiles in terms of model
      fit and discrimination. We recommend using cut points based on the absolute CAC
      amount, and the common CAC cut points of 100 and 400 seem to perform well.

PMID- 19161886
TI  - Heart failure decompensation and all-cause mortality in relation to percent
      biventricular pacing in patients with heart failure: is a goal of 100%
      biventricular pacing necessary?
AB  - OBJECTIVES: The goal of this analysis was to determine the appropriate
      biventricular pacing target in patients with heart failure (HF). BACKGROUND:
      Cardiac resynchronization therapy (CRT) decreases the risk of death and HF
      hospitalization. However, the appropriate amount of biventricular pacing is ill
      defined. METHODS: Mortality and HF hospitalization data from patients undergoing
      CRT in 2 trials (CRT RENEWAL [Cardiac Resynchronization Therapy Registry
      Evaluating Patient Response with RENEWAL Family Devices] and REFLEx [ENDOTAK
      RELIANCE G Evaluation of Handling and Electrical Performance Study]; n = 1,812)
      were analyzed in a post-hoc fashion. Subjects were grouped based on percent
      biventricular pacing quartiles with the use of Kaplan-Meier survival analysis.
      RESULTS: Subjects were age 72 +/- 11 years; 72% were men and 67% had coronary
      artery disease. Subjects paced 93% to 100% (quartiles 2 to 4) had a 44% reduction
      in hazard of an event compared with subjects paced 0% to 92% (quartile 1; hazard
      ratio [HR]: 0.56, p < 0.00001). Subjects paced 98% to 99% (quartile 3) had
      similar outcomes as subjects paced 93% to 97% (quartile 2; HR: 0.97, p = 0.82).
      Subjects paced 100% (quartile 4) had similar outcomes as subjects paced 98% to
      99% (HR: 0.78, p = 0.17). There was a significant interaction between a history
      of atrial arrhythmia and percent pacing. Subjects with a history of atrial
      arrhythmia were more likely to be paced < or =92% (p < 0.001). CONCLUSIONS: For
      CRT patients in this retrospective analysis, the greatest magnitude of benefit
      was observed with >92% biventricular pacing.

PMID- 19161887
TI  - A dose response for cardiac resynchronization therapy?

PMID- 19161888
TI  - Combined effects of tobacco smoke exposure and metabolic syndrome on
      cardiovascular risk in older residents of China.

PMID- 19161889
TI  - Rapidly evolving giant coronary aneurysm.

PMID- 19161890
TI  - Highlights of the Year in JACC 2008.

PMID- 19161892
TI  - Left ventricular mass and the outcome of patients with hypertrophic
      cardiomyopathy.

PMID- 19161893
TI  - Extending the benefits of addiction treatment: practical strategies for
      continuing care and recovery.

PMID- 19161895
TI  - The mobilization of community resources to support long-term addiction recovery.
AB  - Models of addiction treatment that view the sources and solutions to severe
      alcohol and other drug (AOD) problems as rooted within the vulnerability and
      resiliency of each individual stand in marked contrast to models that focus on
      the ecology of AOD problem development and resolution via complex interactions
      between individuals, families, and communities. An integration of the latter
      model into mainstream addiction treatment would necessitate a reconstruction of
      the treatment-community relationship and new approaches to community resource
      development and mobilization. Such an integration would redefine core addiction
      treatment services and to whom, by whom, when, where, and for how long such
      services are delivered. This article draws on historical and contemporary events
      in the history of addiction treatment and recovery in the United States to
      illuminate the relationship between recovery and community. Principles and
      strategies that could guide the development and mobilization of community
      resources to support the long-term recovery of individuals and families are
      identified.

PMID- 19161894
TI  - Continuing care research: what we have learned and where we are going.
AB  - In the field of addiction treatment, the term continuing care has been used to
      indicate the stage of treatment that follows an initial episode of more intensive
      care. This article reviews controlled studies of continuing care conducted over
      the prior 20 years. The results indicate that continuing care interventions were
      more likely to produce positive treatment effects when they had a longer planned
      duration, made more active efforts to deliver treatment to patients, and were
      studied more recently. However, there was considerable variability in patient
      response and room for improvements in participation rates and effectiveness. It
      is possible that the effectiveness of continuing care interventions could be
      further improved by the use of adaptive algorithms, which adjust treatment over
      time based on changes in patients' symptoms and status. The use of alternative
      service delivery methods and care settings may also lead to greater engagement
      and retention in continuing care, particularly among the large numbers of
      individuals who do not want traditional, clinic-based specialty care.

PMID- 19161896
TI  - Setting the standard for recovery: Physicians' Health Programs.
AB  - A sample of 904 physicians consecutively admitted to 16 state Physicians' Health
      Programs (PHPs) was studied for 5 years or longer to characterize the outcomes of
      this episode of care and to explore the elements of these programs that could
      improve the care of other addicted populations. The study consisted of two
      phases: the first characterized the PHPs and their system of care management,
      while the second described the outcomes of the study sample as revealed in the
      PHP records. The programs were abstinence-based, requiring physicians to abstain
      from any use of alcohol or other drugs of abuse as assessed by frequent random
      tests typically lasting for 5 years. Tests rapidly identified any return to
      substance use, leading to swift and significant consequences. Remarkably, 78% of
      participants had no positive test for either alcohol or drugs over the 5-year
      period of intensive monitoring. At post-treatment follow-up 72% of the physicians
      were continuing to practice medicine. The unique PHP care management included
      close linkages to the 12-step programs of Alcoholics Anonymous and Narcotics
      Anonymous and the use of residential and outpatient treatment programs that were
      selected for their excellence.

PMID- 19161897
TI  - State of the science: Extending the benefits of addiction treatment.

PMID- 19161899
TI  - Antipsychotic drugs for dementia: a balancing act.

PMID- 19161900
TI  - JUPITER and the world of stroke medicine.

PMID- 19161901
TI  - Cardiopulmonary surveillance to prevent SUDEP.

PMID- 19161903
TI  - Treatment of community-onset childhood convulsive status epilepticus.

PMID- 19161905
TI  - Unapproved drug use: compassionate or cause for concern?

PMID- 19161906
TI  - Oscar Gershanik: putting Argentina on the world neurology map.

PMID- 19161908
TI  - Cerebral microbleeds: a guide to detection and interpretation.
AB  - Cerebral microbleeds (CMBs) are increasingly recognised neuroimaging findings in
      individuals with cerebrovascular disease and dementia, and in normal ageing.
      There has been substantial progress in the understanding of CMBs in recent years,
      particularly in the development of newer MRI methods for the detection of CMBs
      and the application of these techniques to population-based samples of elderly
      people. In this Review, we focus on these recent developments and their effects
      on two main questions: how CMBs are detected, and how CMBs should be interpreted.
      The number of CMBs detected depends on MRI characteristics, such as pulse
      sequence, sequence parameters, spatial resolution, magnetic field strength, and
      image post-processing, emphasising the importance of taking into account MRI
      technique in the interpretation of study results. Recent investigations with
      sensitive MRI techniques have indicated a high prevalence of CMBs in community
      dwelling elderly people. We propose a procedural guide for identification of CMBs
      and suggest possible future approaches for elucidating the role of these common
      lesions as markers for, and contributors to, small-vessel brain disease.

PMID- 19161909
TI  - The cerebral effects of ascent to high altitudes.
AB  - Cellular hypoxia is the common final pathway of brain injury that occurs not just
      after asphyxia, but also when cerebral perfusion is impaired directly (eg,
      embolic stroke) or indirectly (eg, raised intracranial pressure after head
      injury). We Review recent advances in the understanding of neurological clinical
      syndromes that occur on exposure to high altitudes, including high altitude
      headache (HAH), acute mountain sickness (AMS), and high altitude cerebral oedema
      (HACE), and the genetics, molecular mechanisms, and physiology that underpin
      them. We also present the vasogenic and cytotoxic bases for HACE and explore
      venous hypertension as a possible contributory factor. Although the factors that
      control susceptibility to HACE are poorly understood, the effects of exposure to
      altitude (and thus hypobaric hypoxia) might provide a reproducible model for the
      study of cerebral cellular hypoxia in healthy individuals. The effects of
      hypobaric hypoxia might also provide new insights into the understanding of
      hypoxia in the clinical setting.

PMID- 19161910
TI  - Neuro-Behcet's disease: epidemiology, clinical characteristics, and management.
AB  - Behcet's disease (BD) is a multisystem relapsing inflammatory disorder of unknown
      cause. In neuro-BD (NBD), the CNS can be involved in one or both of two ways:
      first, and most commonly, through the development of an immune-mediated
      meningoencephalitis, which predominantly involves the brainstem, but can also
      involve the basal ganglia, thalamus, cortex and white matter, spinal cord, or
      cranial nerves; and second, as a consequence of thrombosis within the dural
      venous sinuses. Headache is a common symptom in BD and does not necessarily
      indicate CNS involvement. Peripheral nervous system involvement is rare. New
      treatment options have recently become available, which have led to an
      improvement in morbidity after meningoencephalitis. Most of the reported studies
      on NBD are retrospective. Collaborative prospective studies of the natural
      history of the disease, particularly the nature and treatment of progressive
      neurological disease, and evidence-based studies of treatment are needed.

PMID- 19161911
TI  - Matrix metalloproteinases and their multiple roles in neurodegenerative diseases.
AB  - Matrix metalloproteinases (MMPs) and proteins containing a disintegrin and
      metalloproteinase domain (ADAM) are important in neuroinflammation, and recent
      studies have linked their actions to neurodegenerative disorders. MMPs act as
      cell-surface sheddases and can affect cell signalling initiated by growth factors
      or death receptors. Four tissue inhibitors of metalloproteinases (TIMPs) regulate
      metalloproteinase activity. These proteases increase the permeability of the
      blood-brain barrier, which can cause oedema, haemorrhage, and cell death. MMPs
      also participate in tissue repair by promoting angiogenesis and neurogenesis. In
      vascular cognitive impairment, MMPs change permeability of the blood-brain
      barrier and might contribute to white matter damage. MMPs and ADAMs might
      contribute to the formation and degradation of amyloid proteins in Alzheimer's
      disease and cause death of dopaminergic neurons in Parkinson's disease. In this
      Review, by examining the effects of neuroinflammation, we try to understand the
      role that MMPs might have in neurodegenerative diseases. Therapeutic strategies
      that use inhibitors of MMPs could represent potential novel treatments for
      neurological diseases.

PMID- 19161912
TI  - SNE and politics.

PMID- 19161913
TI  - The economic crisis--what is the role for nutrition educators?

PMID- 19161914
TI  - Understanding adherence to 5 servings of fruits and vegetables per day: a theory
      of planned behavior perspective.
AB  - OBJECTIVE: The primary purpose of the present study was to examine the utility of
      the Theory of Planned Behavior (TPB) in explaining the 5-A-Day intentions and
      behavior of college students. A secondary purpose was to determine whether any of
      the TPB relationships were moderated by gender or ethnicity. DESIGN: A
      prospective design that asked college students to complete a baseline TPB 5-A-Day
      questionnaire and a fruit and vegetable consumption measure 1 week later.
      SETTING: Undergraduate fitness and health classes at 2 universities in the
      southern United States. PARTICIPANTS: 511 college students with a mean age of
      19.8 years (standard deviation = 2.71). MAIN OUTCOME MEASURES: TPB variables and
      fruit and vegetable consumption. ANALYSES: Path analyses and invariance (ie, to
      examine ethnic and gender moderated) analyses. RESULTS: Affective attitude (beta
      = .16, P < .05) and perceived behavioral control (beta = .59, P < .05) were
      significant predictors of intention, which in turn was a significant predictor of
      behavior (beta = .32, P < .05). Follow-up invariance analyses showed that none of
      the TPB relationships was moderated by gender or ethnicity. CONCLUSIONS AND
      IMPLICATIONS: The TPB may be a useful framework on which to base a 5-A-Day
      intervention for male and female college students of different ethnic
      backgrounds.

PMID- 19161915
TI  - Characteristics and dietary patterns of adolescents who value eating locally
      grown, organic, nongenetically engineered, and nonprocessed food.
AB  - OBJECTIVE: To examine characteristics of adolescents who value eating locally
      grown, organic, nongenetically engineered, and/or nonprocessed food and whether
      they are more likely than their peers to meet Healthy People 2010 dietary
      objectives. DESIGN: Cross-sectional analysis using data from a population-based
      study in Minnesota (Project EAT: Eating Among Teens). SETTING: Participants
      completed a mailed survey and food frequency questionnaire in 2004. PARTICIPANTS:
      Males and females (N = 2516), ages 15-23 years. MAIN OUTCOME MEASURES: Dietary
      intake of fruit, vegetables, fat, grains, calcium, and fast food. ANALYSIS: Chi
      square tests, logistic regression models adjusting for race/ethnicity,
      socioeconomic status, and vegetarian status. RESULTS: Percentages of adolescents
      who reported that it was somewhat or very important that their food be locally
      grown, organic, nongenetically engineered, and nonprocessed were 20.9%, 23.2%,
      34.1%, and 29.8%, respectively. Those who valued each practice were more likely
      than their peers to be nonwhite (P < .001) and have a low socioeconomic status (P
      < .001). Adolescents who valued >/= 2 practices were more likely than their peers
      to have a dietary pattern consistent with the Healthy People 2010 objectives (P <
      .001) for fruit, vegetable, and fat intake. CONCLUSIONS AND IMPLICATIONS: It may
      beneficial to discuss alternative food production practices as part of nutrition
      education programs for adolescents.

PMID- 19161916
TI  - Parent-reported eating and leisure-time activity selection patterns related to
      energy balance in preschool- and school-aged children.
AB  - OBJECTIVE: Compare parent-reported preschool- and school-aged children's eating
      and leisure-time activity patterns that are proposed to influence energy balance.
      DESIGN: Cross-sectional investigation of children, 2 to 12 years, attending a
      well visit. SETTING: Pediatric private practice/ambulatory pediatric clinic.
      PARTICIPANTS: One hundred seventy-four children: 49% preschool-aged, 54% female,
      28% Hispanic, and 34% overweight or at risk for overweight. VARIABLES MEASURED:
      Parent-reported eating/leisure-time behaviors. Height/weight from medical
      records. ANALYSIS: Analyses of covariance/chi-square tests; significance at P
      <or= .05. RESULTS: By parents' report, preschool-aged children consumed more
      servings/day of low-fat dairy (2.1 +/- 1.6 vs 1.7 +/- 1.5; P < .01), fewer
      servings/day of sweetened drinks (1.4 +/- 1.9 vs 2.2 +/- 2.6; P < .01) and
      watched fewer hours/day of weekend TV (2.3 +/- 1. 3 vs 2.7 +/- 1.3; P < .05) than
      school-aged children. Fewer preschool-aged children consumed salty (14.0% vs
      26.1%; P < .05) and sweet (16.3% vs. 29.5%; P < .05) snack food daily, and a
      greater percentage regularly consumed dinner with a parent (93.0% vs 80.7%; P <
      .05), as assessed by parent report. CONCLUSIONS AND IMPLICATIONS: Parent-reported
      children's eating/leisure-time patterns that may influence energy balance were
      less healthful in the school-aged children. However, most children did not meet
      recommendations, irrespective of age or weight. Interventions for meeting
      recommendations should start with families with preschool-aged children. Future
      research should focus on identifying factors that might be contributing to
      increased reporting of problematic food and leisure-time activity patterns in
      school-aged children.

PMID- 19161917
TI  - In-school snacking, breakfast consumption, and sleeping patterns of normal and
      overweight Iranian high school girls: a study in urban and rural areas in Guilan,
      Iran.
AB  - OBJECTIVE: To investigate the relationship of snacking during school hours, sleep
      time, and breakfast consumption by weight status of Iranian high school girls in
      urban and rural areas in Guilan Province, Iran. DESIGN: Data were collected by
      self-administered questionnaire and measure of body weight and height. SETTING:
      High schools in urban and rural areas in Guilan Province, northern Iran.
      PARTICIPANTS: Representative sample of 2302 school girls (1106 in Rasht City and
      1196 in rural areas) selected by multistage cluster sampling. MAIN OUTCOME
      MEASURES: Breakfast skipping, snacking habits at school, sleep habits, body
      weight, and height. ANALYSIS: Differences in the frequency of the measured
      variables between the urban and rural girls and overweight and normal weight
      girls were tested using the chi-square test, P < .05. RESULTS: Prevalence of
      obesity was significantly (P < .05) lower in urban areas (4.1%) than in rural
      areas (5.2%). Prevalence of overweight was significantly higher in those who
      usually skipped breakfast (P < .001). Consumption of food items of low nutrient
      density as snacks during the school day was common in this population, especially
      in rural areas. CONCLUSION AND IMPLICATIONS: The school environment may
      contribute to the high prevalence of overweight/obesity observed among Iranian
      adolescent females. Students should be encouraged to eat breakfast and choose
      nutritious snacks during the school day.

PMID- 19161919
TI  - Assessing an infant feeding web site as a nutrition education tool for child care
      providers.
AB  - OBJECTIVE: Determine child care providers' infant feeding knowledge, attitude and
      behavior changes after viewing the infant feeding Web site and determine the
      effectiveness of the Web site and bilingual educational materials. DESIGN:
      Intervention and control groups completed an on-line pretest survey, viewed a Web
      site for 3 months, and completed an on-line posttest survey; follow-up data were
      also assessed. SETTING: Colorado child care centers. PARTICIPANTS: Thirty-eight
      child care providers. INTERVENTION: Social learning theory-based website was
      evaluated by child care providers in the treatment group and providers in the
      control group viewed a comparable website. MAIN OUTCOME MEASURES: Knowledge,
      attitude, and behavior changes on feeding infants breast milk, formula, and solid
      food; desired changes to Web site. ANALYSIS: Independent samples t tests, chi
      square, and repeated measures. RESULTS: Changes in attitudes and behaviors from
      pre- to posttest occurred primarily in the intervention group (P < .05). At
      follow-up, no significant differences were found among the 3 time periods.
      Providers desired no changes to Web site or materials. CONCLUSIONS AND
      IMPLICATIONS: Child care providers appeared to have adequate knowledge on feeding
      infants formula and breast milk, but not on hunger cues. Providers would continue
      to use this Web site in the future. Further research should determine if changes
      in knowledge, attitudes, and behaviors are sustained over time and how infant
      feeding cues are read and determined in child care centers.

PMID- 19161918
TI  - Dietary behaviors and portion sizes of black women who enrolled in SisterTalk and
      variation by demographic characteristics.
AB  - OBJECTIVE: To describe the dietary behaviors of black women who enrolled in the
      SisterTalk weight control study. DESIGN: Baseline data collected via telephone
      survey and in-person screening. SETTING: Boston, Massachusetts and surrounding
      areas. PARTICIPANTS: 461 black women completed the baseline assessments. MAIN
      OUTCOME MEASURES: Measured height and weight; self-reported demographics, risk
      factors, and dietary variables including fat-related eating behaviors, food
      portion size, and fruit, vegetable, and beverage intake. ANALYSIS: Analysis of
      variance (ANOVA) models with food habits questionnaire (FHQ) scores as the
      dependent variable and demographic categories as the independent variables; ANOVA
      models with individual FHQ item scores as the dependent variable and ethnic
      identification as the independent variable. RESULTS: More than 60% reported
      eating < 5 servings of fruits and vegetables/day. Self-reported portion sizes
      were large for most food items. Older age, being born outside the United States,
      living without children, and being retired were significantly associated with a
      higher prevalence of fat-lowering behaviors. The frequency of specific fat
      lowering behaviors and portion size also differed by ethnic identification.
      CONCLUSIONS AND IMPLICATIONS: The findings support the need for culturally
      appropriate interventions to improve the dietary intake of black Americans.
      Further studies should examine the dietary habits, food preparation methods, and
      portion sizes of diverse groups of black women.

PMID- 19161920
TI  - Increasing physical activity in preschool: a pilot study to evaluate animal
      trackers.
AB  - OBJECTIVE: This report describes a pilot study to evaluate Animal Trackers (AT),
      a preschool program designed to (1) increase structured physical activity (PA)
      during the preschool day; (2) increase practice of gross motor skills; (3)
      provide teachers with an easy-to-use PA program regardless of teacher experience;
      and (4) implement a teacher walking intervention. DESIGN: Pilot observational
      study in volunteer preschools. SETTING: Nine preschools in New Mexico.
      PARTICIPANTS: Two-hundred seventy 3- to 5-year-old children and 32 teachers.
      INTERVENTION: Daily 10-minute classroom activities for children. MAIN OUTCOME
      MEASURE: Implementation and duration of AT activities, teacher preparation time,
      and added weekly time spent in structured PA. ANALYSIS: Process evaluation to
      track program implementation, and pre-post measures to assess outcomes. RESULTS:
      AT activities were implemented 4.1 times per week (11.4 minutes/activity), with 7
      minutes teacher preparation time. Overall, AT added 47 minutes of structured PA
      per week for children. CONCLUSIONS AND IMPLICATIONS: The AT program increased
      structured PA time in preschools. Teachers felt that AT was developmentally
      appropriate; that children enjoyed the activities; and that the children's motor
      skills improved. Results of the pilot study are encouraging, since research
      suggests that even small increases in PA could help prevent obesity.

PMID- 19161921
TI  - Parental influences on dairy intake in children, and their role in child calcium
      fortified food use.
AB  - OBJECTIVE: To understand how parental influences on dairy food intake relate to
      early adolescent children's use of calcium-fortified food. DESIGN: Content
      analysis of qualitative interviews to identify parental influences on dairy
      intake; calcium-fortified food survey to identify children as either calcium
      fortified food users or nonusers. SETTING AND PARTICIPANTS: A convenience sample
      of Asian (n = 56), Hispanic (n = 61), and white (n = 74) parents of children 10
      13 years old, including boys (n = 86) and girls (n = 105). VARIABLES MEASURED AND
      ANALYSIS: Cluster analysis to identify groups with similar coded parental
      influences and chi-square analysis to determine associations between these groups
      and calcium-fortified food use. RESULTS: Two dominant patterns of parental
      influences: Cluster 1 (n = 128), with positive parental influences related to
      availability of dairy, milk, and cheese; positive health beliefs for dairy, and
      child preferences for dairy and cheese, included parents whose children were more
      likely to use calcium-fortified food. Cluster 2 (n = 63), with positive
      influences for availability of dairy and milk, included parents whose children
      were equally likely to be either users or nonusers of calcium-fortified food (P <
      .05). CONCLUSION: Strategies to improve parental influence on children's dairy
      intake might also encourage calcium-fortified food intake and improve calcium
      nutriture.

PMID- 19161922
TI  - Health behaviors, nutritional status, and anthropometric parameters of Roma and
      non-Roma mothers and their infants in the Czech Republic.
AB  - OBJECTIVE: To compare maternal health behaviors, maternal nutritional status, and
      infant size at birth of Romas and non-Romas in the Czech Republic. DESIGN:
      Maternal interviews and food frequency questionnaire, maternal blood samples,
      physical measurements of mothers and infants. SETTING: Hospital, maternal/child
      care center; 2-4 days postpartum. PARTICIPANTS: 76 Roma mothers and 151 mothers
      from the majority population. MAIN OUTCOME MEASURES: Infant length/weight;
      maternal height/weight; weight gain during pregnancy; duration of pregnancy;
      maternal smoking habits; dietary intake; use of food supplements during
      pregnancy; and maternal blood levels of folate, beta-carotene, retinol, and alpha
      tocopherol. ANALYSIS: Comparison of ethnic groups by 2-sample Wilcoxon test, chi
      square, Fischer's exact test, relative risk, and analysis of variance (ANOVA).
      RESULTS: Pregnancy duration was about 1 week shorter in Roma women (P < .001),
      and their infants had lower birth weight (P < .001) and shorter length (P <
      .001). Prevalence of smoking was significantly higher among Roma mothers (P <
      .001). Roma women used food supplements less frequently than non-Roma women (P <
      .001) and had significantly lower mean blood concentrations of folate (P < .001),
      beta-carotene (P < .001), retinol (P < .02), and alpha-tocopherol (P < .02).
      CONCLUSIONS AND IMPLICATIONS: The nutritional status of Roma mothers is worse
      than that of mothers from the majority Czech population. The dietary and smoking
      habits of pregnant Roma women should be of special concern to family doctors,
      obstetricians, nutrition educators, and social workers.

PMID- 19161923
TI  - Promoting better family meals for girls attending summer programs.

PMID- 19161924
TI  - Peer education, exercising, and eating right (PEER): training of peers in an
      undergraduate faculty teaching partnership.

PMID- 19161925
TI  - Integrating nutrition education into a faith-based prostate screening program: a
      strategy for reaching African American men.

PMID- 19161926
TI  - Osteoporosis pharmacotherapy and counseling services in US ambulatory care
      clinics: opportunities for multidisciplinary interventions.
AB  - OBJECTIVE: This study was conducted to assess rates and predictors of
      osteoporosis management with medication or nonmedication therapy, and to compare
      rates of medication and nonmedication therapy in office-based and hospital-based
      ambulatory care settings in the United States. METHODS: This cross-sectional
      study included data on all ambulatory office visits made by patients aged >or=60
      years in 2000-2005 in 2 national survey databases representing US ambulatory
      clinics. Visits with and without a record of anti-osteoporosis medication were
      identified, and bivariate and multivariate analyses were performed to determine
      predictive factors for receipt of medication or nonmedication therapy for the
      prevention and treatment of osteoporosis. RESULTS: During 2000-2005, visits by
      patients with a diagnosis of osteoporosis or fragility fracture represented <2%
      of all visits in office- and hospital-based ambulatory care settings. Medication
      therapy for osteoporosis was documented in 53.2% of these visits, and
      nonmedication therapy was documented in 31.5%. The most frequently prescribed
      drug class was bisphosphonates (36.0%), followed by calcium and vitamin D
      supplementation (23.9%). The most commonly used nonmedication therapies were
      exercise (16.7%) and diet/nutrition counseling (19.4%). Rates of medication
      therapy did not differ significantly by ambulatory care setting. However, visits
      to hospital-based clinics were significantly less likely than visits to office
      based clinics to involve nonmedication therapy (adjusted odds ratio [OR] = 0.6;
      95% CI, 0.5-0.9; P = 0.004). Compared with visits by women, visits by men were
      significantly less likely to involve medication therapy (adjusted OR = 0.6; 95%
      CI, 0.4-0.9; P = 0.013), nonmedication therapy (adjusted OR = 0.3; 95% CI, 0.2
      0.6; P < 0.001), or any therapy (adjusted OR = 0.4; 95% CI, 0.3-0.6; P<0.001).
      Patients aged >or=80 years were significantly less likely to receive
      nonmedication therapy than were those aged 60 to 69 years (adjusted OR = 0.6; 95%
      CI, 0.4-0.9; P = 0.023). Visits by patients with public insurance were
      significantly less likely to involve medication therapy than visits by patients
      with other sources of payment (adjusted OR = 0.7; 95% CI, 0.5-1.0; P = 0.040). No
      difference in the prevalence of any type of therapy was observed in relation to
      race. CONCLUSIONS: Based on the prevalence of medication and nonmedication
      therapies, levels of osteoporosis care did not differ by ambulatory care setting.
      However, patterns of care varied by certain visit characteristics, including
      insurance type, age, and sex.

PMID- 19161927
TI  - Appropriate proton pump inhibitor use among older adults: a retrospective chart
      review.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) are widely used, but not always with a
      clear indication. Nonindicated use is of particular concern among older adults,
      who may have multiple comorbidities and take more medications, increasing their
      risk for adverse drug reactions. OBJECTIVE: This study examined the
      appropriateness of PPI use at an outpatient geriatric practice and the
      association between particular patient characteristics and appropriate use of
      these medications. METHODS: This was a retrospective chart review of a group of
      randomly identified community-dwelling adults aged >or=65 years with a current
      prescription for a PPI (as of August 2006) from a geriatric ambulatory care
      practice within an urban academic medical center. The main outcome was
      appropriateness of PPI use, categorized as indicated, possibly indicated, or not
      indicated, based on US Food and Drug Administration-approved indications and
      national gastroenterology guidelines. RESULTS: Out of approximately 2500 patients
      in the geriatric practice, 702 (approximately 28%) were identified as having a
      current prescription for a PPI. From these, 110 charts were randomly selected for
      review, of which 10 were excluded based on predefined criteria. The sample was
      79% female and 46% white, with a mean age of 82.8 years (range, 66-99 years). PPI
      use was indicated in 64% of these patients, possibly indicated in 7%, and not
      indicated in 29%. Compared with indicated PPI use, nonindicated use was
      significantly associated with use for <1 year (relative risk = 2.20; 95% CI, 1.00
      4.86; P = 0.05). Nonindicated PPI use was not significantly associated with age,
      female sex, nonwhite race, or PPI initiation in the inpatient setting.
      CONCLUSION: Almost 30% of patients receiving a PPI in this academic geriatric
      practice had no documented indication for PPI use.

PMID- 19161929
TI  - An elderly patient with fluoroquinolone-associated achilles tendinitis.
AB  - BACKGROUND: Due to their broad-spectrum activity and oral bioavailability,
      fluoroquinolone antibiotics are commonly prescribed to adults aged >60 years for
      many common community-acquired infections. The association between
      fluoroquinolone use and Achilles tendinitis is well established but sometimes
      missed in clinical practice. Older patients and patients with renal dysfunction
      are at particularly increased risk for this complication. CASE SUMMARY: We
      present a case of Achilles tendinitis in a 77-year-old patient with renal
      dysfunction and a urinary tract infection (UTI) treated with ciprofloxacin 250 mg
      PO QD. Tendinitis developed within several days of the start of treatment and
      improved within 2 days of treatment cessation, without the need for intervention.
      The likelihood of ciprofloxacin having caused this reaction was probable (Naranjo
      score, 7). Early diagnosis and treatment cessation might have prevented tendon
      rupture, and the tendinitis resolved completely with subsequent physical therapy.
      CONCLUSION: Based on this outcome in this patient with UTI, fluoroquinolones
      should be used with caution, particularly in patients with risk factors
      predisposing to tendinitis, including advanced age and renal dysfunction.

PMID- 19161928
TI  - Factors associated with adherence to medication regimens in older primary care
      patients: the Steel Valley Seniors Survey.
AB  - OBJECTIVE: The aim of this study was to explore associations between 2 specific
      cognitive domains and aspects of medication management among older primary care
      patients. METHODS: A sample of patients aged >or=65 years drawn from several
      small-town primary care practices was carefully characterized by cognitive
      testing and use of prescription medications. Two primary outcome variables were
      examined: (1) self-reports of setting up schedules to manage their own
      medications and (2) overall research assessment of adherence to prescribed
      medications. Predictor variables included scores on tests of verbal memory
      (Hopkins Verbal Learning Test) and executive function (Part B of the Trail Making
      Test); prescription insurance status; number of medications; and dosing
      frequency, adjusting for age, sex, and level of education. Multiple logistic
      regression and generalized estimating equation models were used for multivariable
      analyses. RESULTS: The analytic sample included 343 patients (238 women, 105 men;
      mean [SD] age, 77.52 [6.71] years). Higher scores on the verbal memory test were
      independently associated with successfully setting up a medication schedule,
      after adjusting for covariates (compared with scores in the <10th percentile,
      odds ratio [OR] for scores between the 10th and 50th percentiles: 5.02 [95% CI,
      2.22-11.33; P < 0.001]; OR for scores in the >50th percentile: 6.52 [95% CI, 2.76
      15.42; P < 0.001]). Higher scores on the executive function test were associated
      with treatment adherence (compared with scores in the <10th percentile, OR for
      scores between the 10th and 50th percentiles: 3.25 [95% CI, 1.13-9.33; P = 0.03];
      OR for scores in the >50th percentile: 4.32 [95% CI, 2.76-15.68; P = 0.02]).
      Compared with using <or=4 prescription drugs, using >or=5 drugs was also
      associated with poor adherence (OR: 0.45 [95% CI, 0.21-0.95; P = 0.04]) as
      measured by research nurses' assessment of adherence. CONCLUSIONS: In this sample
      of older patients assessed for medication management, independent cognitive
      processes were associated with the ability to set up a medication schedule and
      overall adherence to prescriptions. Better verbal memory functioning was strongly
      and independently associated with setting up a medication schedule, while better
      executive functioning was strongly and independently associated with being fully
      adherent to prescription instructions. Deficits in either cognitive ability could
      result in medication errors due to nonadherence.

PMID- 19161930
TI  - Inappropriate sexual behaviors in cognitively impaired older individuals.
AB  - BACKGROUND: Agitated and aggressive behaviors are common in older patients with
      dementia (33% of the community-dwelling and 80% of the institutionalized
      populations). Although inappropriate verbal and physical sexual behaviors are
      among the least common of these actions, they can be profoundly disruptive to
      caregivers (spouse, institutional staff, or both) and other individuals in the
      immediate surroundings. Substantial mental and physical harm can occur secondary
      to these behaviors. The common perception is that such behavior cannot be
      treated. OBJECTIVE: This review summarizes the epidemiology, etiology, and
      biology of abnormal sexual behaviors in cognitively impaired older individuals
      and highlights potentially useful drug therapies. METHODS: Primary research and
      review articles in the English language were identified through a search of
      MEDLINE/PubMed (1966-September 2008). Search terms included aged, hypersexuality,
      sexual disorders, paraphilia, sexual behaviors, tricyclic antidepressants,
      selective serotonin reuptake inhibitors, medroxyprogesterone acetate, cyproterone
      acetate, estrogens, LHRH agonists, leuprolide, and triptorelin. The
      bibliographies of all articles obtained were also reviewed for relevant
      citations. All articles involving abnormal sexual behaviors in older humans were
      reviewed. RESULTS: Use of pharmacotherapy in managing inappropriate sexual
      behaviors in cognitively impaired older individuals has been detailed in only 23
      case reports and case series (N = 55 subjects). Additional supportive data from
      case reports and case series are available in nonsexual agitation/aggression in
      elderly patients with dementia (N = 16 subjects) and abnormal sexual behaviors in
      cognitively intact elderly (N = 2 subjects). One comparative trial in nonsexual
      agitation/aggression in elderly patients with dementia also exists (N = 27
      subjects). There are no practice guidelines available for the treatment of
      abnormal sexual behaviors in the cognitively impaired elderly population.
      Recommendations must be individualized on the basis of clinical exigency and
      pragmatism; they should also be predicated on medical clearance to use estrogen
      or antiandrogen (progestogen, luteinizing hormone-releasing hormone [LHRH]
      agonist) therapies, if necessary. Very few data exist regarding the treatment of
      females of any age exhibiting abnormal sexual behaviors. For males, reasonable
      data support the use of serotoninergics (eg, tricyclic antidepressants [TCAs],
      selective serotonin reuptake inhibitors [SSRIs]), estrogens (oral, transdermal),
      antiandrogens (cyproterone acetate, medroxyprogesterone acetate), and the LHRH
      agonists (eg, leuprolide, triptorelin). Comparative trial data, both within and
      between these drug classes from the paraphilia literature, provide additional
      information that can be used to generate at least a provisional approach to drug
      treatment of abnormal sexual behaviors in older subjects with impaired cognition.
      CONCLUSIONS: In general, unless the patient is engaging in or threatening
      dangerous acts involving physical contact, serotoninergics (first choice, SSRIs;
      second choice, TCAs) are first-line agents followed by antiandrogens (cyproterone
      acetate or medroxyprogesterone acetate) as second-line agents. LHRH agonists
      (first choice) and estrogens (second choice) are considered third-line agents.
      Combination therapy is reasonable if the patient fails to respond to monotherapy.

PMID- 19161932
TI  - Effect of laparoscopic Roux-en-Y gastric bypass surgery on hemoglobin A1c levels
      in diabetic patients: a matched-cohort analysis.
AB  - BACKGROUND: Elevated hemoglobin A1c (HbA1c) values are known to increase the risk
      of diabetic retinopathy, nephropathy, and peripheral neuropathy. The current
      guidelines recommend maintaining HbA1c values at <7%. We assessed the effect of
      laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) on HbA1c values in diabetic
      patients compared with a conventionally treated cohort. METHODS: A retrospective
      review of a prospective bariatric database identified diabetic patients who had
      undergone LRYGB from 2001 to 2005. A cohort of conventionally treated obese (body
      mass index >35 kg/m(2)) diabetic patients was matched by age and gender. The
      inclusion criteria consisted of a preoperative/initial HbA1c and 2
      postoperative/follow-up HbA1c values compiled from our institution's
      comprehensive electronic medical record system. The patients in the LRYGB cohort
      were also required to have had a 1-year postoperative weight recorded.
      Statistical analysis was performed using the Student t test. RESULTS: Each cohort
      consisted of 40 women (78.4%) and 11 men (21.6%). The mean age was 48.8 +/- 8.3
      years for the surgical cohort and 48.2 +/- 8.3 years for the conventionally
      treated cohort. The mean body mass index was 47.7 +/- 5.7 kg/m(2) preoperatively
      for the surgical cohort and 45.1 +/- 5.7 kg/m2 initially for the conventionally
      treated cohort. The mean preoperative/initial HbA1c was 7.5% +/- 1.4% and 7.0% +/
      1.1% for the surgical and conventionally treated groups, respectively. At 1
      year, HbA1c results were available for 46 LRYGB and 41 conventionally treated
      patients. The corresponding mean HbA1c values were 5.8% +/- 1.1% and 7.0% +/- .9%
      (P = .001). At 3 years, the mean HbA1c was 6.1% +/- 1.2% and 7.8% +/- 1.5% for 28
      surgical and 36 conventionally treated patients, respectively (P = .001). The
      surgical patients' use of oral hypoglycemic medications and/or insulin decreased
      from 84.3% before surgery to 22.4% at 1 year postoperatively. CONCLUSION: The
      patients who underwent LRYGB had a significant and sustained improvement in the
      HbA1c value compared with the conventionally treated obese patients with type 2
      diabetes mellitus.

PMID- 19161933
TI  - Metabolic surgery: not just weight loss surgery anymore.

PMID- 19161934
TI  - Safety and efficacy of simultaneous cholecystectomy at Roux-en-Y gastric bypass.
AB  - BACKGROUND: To date, published reports have shown an increased length of hospital
      stay and increased morbidity for patients undergoing simultaneous cholecystectomy
      during Roux-en-Y gastric bypass (RYGB). We hypothesized that our experience would
      not show such adverse outcomes. METHODS: All RYGB procedures (n = 752) performed
      by 1 surgeon at our institution from 1995 to 2006 were reviewed for demographic
      data, operative data, and postoperative outcomes. A laparoscopic approach (LRYGB)
      was used for 438 procedures. The data from a prospectively gathered institutional
      database were retrospectively compared using standard statistical analysis.
      RESULTS: Comparing LRYGB with cholecystectomy to LRYGB without cholecystectomy,
      the operative time was significantly longer (198.4 +/- 61.9 versus 177.7 +/- 57.7
      min, P = .001), but the mean hospital stay (3.3 +/- 5.5 versus 2.9 +/- 6.1 d, P =
      .555), postoperative complication rate (18.3% versus 18.5%, P = .100), and
      postoperative mortality (0% and .6%, P = 1.000) were not different between the 2
      groups. Comparing the open RYGB patients with and without simultaneous
      cholecystectomy, the operative time was similarly longer (223.4 +/- 63.9 versus
      203.5 +/- 57.3 min, P = .005), and the mean hospital stay (5.0 +/- 3.7 versus 4.7
      +/- 5.9 d, P = .644), postoperative complication rate (61.4% versus 55.2%, P =
      .293), and postoperative mortality rate (1.6% versus 2.4%, P = .685) were not
      different between the 2 groups. CONCLUSION: Although it took, on average, 20
      minutes longer, cholecystectomy can be safely added to RYGB without increasing
      the hospital stay, postoperative morbidity, or mortality in both laparoscopic and
      open surgery using comparable operative techniques. We recommend routine
      simultaneous cholecystectomy be performed for patients with documented gallstones
      during RYGB.

PMID- 19161935
TI  - Updated Bariatric Analysis and Reporting Outcome System (BAROS).
AB  - BACKGROUND: The Bariatric Analysis and Reporting Outcome System (BAROS) evaluates
      the results of obesity treatments by analyzing 3 domains: weight loss, changes in
      co-morbidities, and quality of life. Up to 3 points are allowed for each, and
      points are deducted for complications and reoperations. The final score
      classifies the results in 5 outcome groups, providing an objective definition of
      success or failure. This report describes refinements to the original instrument.
      METHODS: The system has been used in many countries since the late 1990s.
      Feedback from its users and additional research prompted some changes. The
      quality of life questionnaire was tested in clinical practice in United States
      and Austria, which led to improvements. It was later compared with other
      instruments for validity and reliability using a group of 110 gastric bypass
      patients. RESULTS: The updated BAROS includes the percentage of excess body mass
      index loss, new criteria for the diagnosis of diabetes, and clarifies the concept
      of its "improvement." The wording and drawings in the quality-of-life
      questionnaire were modified. A sixth question, analyzing eating behavior, was
      added, and the scoring key was changed to a 10-point Likert scale, creating the
      Moorehead-Ardelt Quality of Life Questionnaire II. The new instrument correlated
      significantly with the Medical Outcomes Study Short Form 36-item Health Survey,
      the Beck Depression Inventory II, and the Stunkard and Messick Eating Inventory.
      CONCLUSION: The BAROS is very useful for evaluating and reporting the results of
      obesity treatments. It can be used to measure the outcomes of > or =1 operations
      and to compare the results among different surgeons, regardless of their
      location. If this is corroborated by generalized use of the system, the BAROS can
      contribute to a uniform assessment of outcomes.

PMID- 19161936
TI  - Feasibility and technique of laparoscopic conversion of adjustable gastric
      banding to sleeve gastrectomy.
AB  - BACKGROUND: To evaluate the feasibility, safety, and short-term efficacy of the
      conversion of laparoscopic adjustable gastric banding (LAGB) to laparoscopic
      sleeve gastrectomy (LSG) because of inadequate weight loss. METHODS: The
      inclusion criteria were an inadequate percentage of excess weight loss (%EWL),
      defined as <30% at > or =1 year after LAGB. From August 2002 to October 2007, 27
      patients (17 women and 10 men) had undergone removal of their LAGB and conversion
      to LSG. The average age at LSG was 43.6 +/- 11.4 years (range 25-66). Before
      LAGB, the mean weight and body mass index was 129.8 +/- 21.9 kg (range 95-178)
      and 45 +/- 8.1 kg/m(2) (range 35-64), respectively. The average interval between
      LAGB and LSG was 51.2 +/- 30.1 months (range 22-132). Before conversion, the mean
      weight, body mass index, and %EWL was 117.9 +/- 27.3 kg (range 63-170), 39 +/-
      9.6 kg/m2 (range 24-61), and 18.1% +/- 18.3%, respectively. Of the 27 patients,
      12 had 19 obesity-related co-morbidities, including arterial hypertension in 7,
      type 2 diabetes mellitus in 2, degenerative joint disease in 7, and sleep apnea
      in 3. RESULTS: The mean operative time was 120.6 +/- 32.4 minutes (range 65-195).
      No conversion to open surgery was required, and no patient died. The
      postoperative complications included a subphrenic hematoma that required
      laparoscopic drainage; no postoperative leaks developed. The mean hospital stay
      was 3.2 +/- 1.4 days (range 2-8). After a mean follow-up of 18.6 +/- 14.8 months
      (range 1-59) for 23 patients (4 patients were lost to follow-up), the mean
      weight, body mass index, and weight loss was 100.7 +/- 23.5 kg (range 61-152),
      34.6 +/- 8.7 kg/m2 (range 21-50.4), and 23 +/- 12.4 kg (range 2-55),
      respectively. The patients had had an additional 16.7% EWL after LSG for a total
      average %EWL of 34.8% +/- 21.8% (P <.05). Of the 12 patients with obesity-related
      co-morbidities, 5 had had resolution, including arterial hypertension in 1, type
      2 diabetes mellitus in 1, degenerative joint disease in 2, and sleep apnea in 2.
      CONCLUSION: The results of this study support the safety of LSG in the case of an
      inadequate %EWL after LAGB. However, the degree of weight loss and co-morbidity
      resolution is of concern.

PMID- 19161937
TI  - Comment on: when is the best time to deliver behavioral intervention to bariatric
      surgery patients: before or after surgery?

PMID- 19161938
TI  - Laparoscopic reduction of small bowel intussusception in a 33-week pregnant
      gastric bypass patient: surgical technique and review of literature.

PMID- 19161939
TI  - Cushing syndrome and bariatric surgery: why, when, and how to evaluate
      preoperatively.

PMID- 19161940
TI  - Small but influential: the role of microRNAs on gene regulatory network and 3'UTR
      evolution.
AB  - MicroRNAs (miRNAs) are endogenous approximately 22 nucleotide noncoding RNAs that
      regulate the expression of complementary messenger RNAs (mRNAs). Thousands of
      miRNA genes have been found in diverse species, and many of them are highly
      conserved. With the miRNA roles identified in nearly all aspects of biological
      processes, evidence is mounting that miRNAs could represent a new layer of
      regulatory network, and their regulatory effect might be much more pervasive than
      previously suspected. Here we focus on the post-transcriptional level gene
      regulation of miRNAs in animals and review how the miRNAs act to sustain and
      shape up the expression profiles of specific cell types; how the miRNAs integrate
      into the existing gene regulatory networks; and how the miRNAs influence the
      evolution of 3'UTR of mammalian mRNAs.

PMID- 19161941
TI  - Molecular characterization and expression analysis of a chicken-type lysozyme
      gene from housefly (Musca domestica).
AB  - Lysozymes can hydrolyze bacteria and play an important role in animal digestion
      and innate immunity. The cDNA of a chicken-type lysozyme gene (Mdlys) was cloned
      from housefly (Musca domestica). The 484 bp full-length cDNA contains a 426 bp
      open reading frame (ORF) that encodes MdLys of 141 amino acids. Phylogenetic
      analysis indicated that the MdLys was similar to chicken-type lysozymes. Spatio
      temporal expression of Mdlys was analyzed by RT-PCR. The Mdlys transcript can be
      detected in both midgut and fat body and was expressed at a relatively lower
      level at the embryo stage. Mdlys mRNA was upregulated 2 h post bacterial
      challenge, maintained for 2 to 6 h, and slightly declined from 12 to 24 h post
      injection. Western blot analysis showed that MdLys was highly expressed in midgut
      and was also detected in the hemolymph and fat body. MdLys expression was
      slightly increased in midgut after challenging with Escherichia coli or
      Staphylococcus aureus. Its expression was also slightly increased in the fat body
      after challenging with S. aureus, but no obvious change occurred after E. coli
      challenge. MdLys expression in the hemolymph was not affected by bacterial
      challenge. In the developmental stages, MdLys expression levels had no obvious
      change from the first instar to the pupae stage. There was also no variation
      under 24 h starvation stress. Recombinant MdLys displayed inhibitory activity
      against Gram-negative and Gram-positive bacteria. Together, these results suggest
      that MdLys may play an important role in the innate immunity of houseflies.

PMID- 19161942
TI  - Transgenic expression of MYB15 confers enhanced sensitivity to abscisic acid and
      improved drought tolerance in Arabidopsis thaliana.
AB  - Abiotic stresses cause serious crop losses. Knowledge on genes functioning in
      plant responses to adverse growth conditions is essential for developing stress
      tolerant crops. Here we report that transgenic expression of MYB15, encoding a
      R2R3 MYB transcription factor in Arabidopsis thaliana, conferred hypersensitivity
      to exogenous abscisic acid (ABA) and improved tolerance to drought and salt
      stresses. The promoter of MYB15 was active in not only vegetative and
      reproductive organs but also the guard cells of stomata. Its transcript level was
      substantially upregulated by ABA, drought or salt treatments. Compared with wild
      type (WT) control, MYB15 overexpression lines were hypersensitive to ABA in
      germination assays, more susceptible to ABA-elicited inhibition of root
      elongation, and more sensitive to ABA-induced stomatal closure. In line with the
      above findings, the transcript levels of ABA biosynthesis (ABA1, ABA2), signaling
      (ABI3), and responsive genes (AtADH1, RD22, RD29B, AtEM6) were generally higher
      in MYB15 overexpression seedlings than in WT controls after treatment with ABA.
      MYB15 overexpression lines displayed improved survival and reduced water loss
      rates than WT control under water deficiency conditions. These overexpression
      lines also displayed higher tolerance to NaCl stress. Collectively, our data
      suggest that overexpression of MYB15 improves drought and salt tolerance in
      Arabidopsis possibly by enhancing the expression levels of the genes involved in
      ABA biosynthesis and signaling, and those encoding the stress-protective
      proteins.

PMID- 19161943
TI  - Expression of a rice OsARGOS gene in Arabidopsis promotes cell division and
      expansion and increases organ size.
AB  - The ARGOS gene in Arabidopsis plays a key role in controlling plant organ size.
      To determine the function of it's ortholog in rice, a putative ARGOS orthologous
      gene from rice tissues was isolated and designated as OsARGOS. This gene has only
      one copy in the rice genome. OsARGOS transcripts were detected in most of rice
      tissues, particularly in the young tissues, and its expression was induced in
      rice seedlings by the application of either auxin or cytokinin. Arabidopsis
      plants expressing OsARGOS led to larger organs, such as leaves and siliques,
      compared with wild-type plants. Interestingly, the root growth was also enhanced
      in these transgenic Arabidopsis plants. Therefore, the biomass of the transgenic
      plants was significantly increased. Further analysis revealed that, different
      from the ARGOS and ARGOS-LIKE genes in Arabidopsis, the OsARGOS gene enlarged
      organ by an increase in both cell number and cell size. In addition, the
      transcript levels of several organ size-associated genes regulating either cell
      division or cell growth were upregulated in the transgenic Arabidopsis plants. We
      also transferred the OsARGOS gene to rice, but the transgenic plants did not show
      any changes in organ size compared with the control plants. It is likely that the
      function of OsARGOS in organ size control depends on other size regulators in
      rice. The expression of OsARGOS in Arabidopsis may activate the signaling
      pathways that control cell proliferation and cell expansion during the course of
      plant growth and development. Since the expression of OsARGOS causes organ
      enlargement, the potential application of this gene through genetic engineering
      may significantly improve the production of biomass in agricultural practice.

PMID- 19161944
TI  - Index selection on seed traits under direct, cytoplasmic and maternal effects in
      multiple environments.
AB  - Crop seeds are important sources of protein, oil, and carbohydrates for food,
      animal feeds, and industrial products. Recently, much attention has been paid to
      quality and functional properties of crop seeds. However, seed traits possess
      some distinct genetic characteristics in comparison with plant traits, which
      increase the difficulty of genetically improving these traits. In this study,
      diallel analysis for seed models with genotype by environment interaction (GE)
      effect was applied to estimate the variance-covariance components of seed traits.
      Mixed linear model approaches were used to estimate the genetic covariances
      between pair-wise seed and plant traits. The breeding values (BV) were divided
      into two categories for the seed models. The first category of BV was defined as
      the combination of direct additive, cytoplasmic, and maternal additive effects,
      which should be utilized for selecting stable cultivars over multi-environments.
      The three genetic effects, together with their GE interaction, were included in
      the second category of BV for selecting special lines to be grown in specific
      ecosystems. Accordingly, two types of selection indices for seed traits, i.e.,
      general selection index and interaction selection index, were developed and
      constructed on the first and the second category BV, respectively. These proposed
      selection indices can be applied to solve the difficult task of simultaneously
      improving multiple seed traits in various environments. Data of crop seeds with
      regard to four seed traits and four yield traits based on the modified diallel
      crosses in Upland cotton (Gossypium hirsutum L.) were used as an example for
      demonstrating the proposed methodology.

PMID- 19161945
TI  - Polymorphic Alu insertions and their associations with MHC class I alleles and
      haplotypes in Han and Jinuo populations in Yunnan Province, southwest of China.
AB  - The associations of polymorphic Alu insertions (POALINs) with major
      histocompatibility complex (MHC) class I genes enable us to better identify
      origins and evolution of MHC class I region haplotypes in different populations.
      For further studying origins and evolution of MHC class I region haplotypes in
      Han and Jinuo populations in Yunnan Province, we investigated frequencies of five
      POALINs, their associations with HLA-A and -B, the three-loci POALINs haplotype
      frequencies and HLA/POALIN four-loci haplotype frequencies within the alpha block
      of MHC class I region. We found that a strong positive association between AluHG
      and HLA-A*02 is in Jinuo, but not in Yunnan Han. These results suggest that MHC
      class I region haplotypes of the two studied populations might derive from
      different progenitor haplotypes and MHC I-POALINs are informative genetic markers
      for investigating origins and evolution of MHC class I region haplotypes in
      different populations.

PMID- 19161946
TI  - Climate change and health: Priorities for the CAM community.
AB  - This article builds on recent discussions published in academic journals on
      climate change and health. It introduces four categories within which the CAM
      community might establish priorities - tactics, specialties, places, research.
      Within each category, the most pressing issues are highlighted and the ways in
      which individuals and the sector might respond.

PMID- 19161947
TI  - An examination of antibacterial and antifungal properties of constituents of
      Shiitake (Lentinula edodes) and oyster (Pleurotus ostreatus) mushrooms.
AB  - BACKGROUND: Antibiotic agents have been in widespread and largely effective
      therapeutic use since their discovery in the 20th century. However, the emergence
      of multi-drug resistant pathogens now presents an increasing global challenge to
      both human and veterinary medicine. It is now widely acknowledged that there is a
      need to develop novel antimicrobial agents to minimize the threat of further
      antimicrobial resistance. With this in mind, a study was undertaken to examine
      the antimicrobial properties of aqueous extracts of 'exotic' Shiitake and Oyster
      mushrooms on a range of environmental and clinically important microorganisms.
      METHOD: Several batches of Shiitake and oyster mushrooms were purchased fresh
      from a local supermarket and underwent aqueous extraction of potential
      antimicrobial components. After reconstitution, aqueous extracts were tested
      qualitatively against a panel of 29 bacterial and 10 fungal pathogens, for the
      demonstration of microbial inhibition. RESULTS: Our data quantitatively showed
      that Shiitake mushroom extract had extensive antimicrobial activity against 85%
      of the organisms it was tested on, including 50% of the yeast and mould species
      in the trial. This compared favourably with the results from both the Positive
      control (Ciprofloxacin) and Oyster mushroom, in terms of the number of species
      inhibited by the activity of the metabolite(s) inherent to the Shiitake mushroom.
      CONCLUSIONS: This small scale study shows the potential antimicrobial effects of
      Shitake extracts, however further work to isolate and identify the active
      compound(s) now requires to be undertaken. Once these have been identified,
      suitable pharmaceutical delivery systems should be explored to allow concentrated
      extracts to be prepared and delivered optimally, rather than crude ingestion of
      raw material, which could promote further bacterial resistance.

PMID- 19161948
TI  - Overseas Chinese students in the UK: patterns and correlates of their use of
      Western and traditional Chinese medicine.
AB  - We explored the correlates of use of TCM and WM by ethnic Chinese students in the
      UK. A questionnaire assessed key theoretical determinants of health services use.
      One hundred and seventy ethnic Chinese participants (international students at
      one university in the South of England) completed this questionnaire (presented
      in English and Chinese) assessing their demographic characteristics, health
      status, attitudes towards and use of TCM and WM. Participants were more likely to
      use WM than TCM when they were in the UK. Different variables predicted use of WM
      and TCM. The statistical predictors (demographic characteristics, health status,
      past behaviour, attitudes) explained modest but important proportions of the
      variance in use of WM (37%) and TCM (29%). In conclusion, this small exploratory
      study suggests a need for further research on the health care utilisation of this
      growing body of international students. Improved language support is needed for
      international students in UK health care settings.

PMID- 19161949
TI  - Reflexology and progressive muscle relaxation training for people with multiple
      sclerosis: a crossover trial.
AB  - PURPOSE: To compare the effects of reflexology and progressive muscle relaxation
      training for people with multiple sclerosis, provided by nurse therapists, on
      psychological and physical outcomes. METHODS: A crossover design was chosen with
      a 4-week break between treatment phases. The Short Form 36 and General Health
      Questionnaire 28 were completed by patients (n=50) pre and post each of the 6
      week treatment phases. Salivary cortisol levels, State Anxiety Inventory,
      systolic and diastolic blood pressure and heart rate data were collected pre and
      post the weekly sessions. RESULTS: All of the chosen measures except for three SF
      36 scales recorded significant changes, however, despite the 4-week break
      (washout period), most outcome measures did not return to their pre-treatment
      baseline levels. This meant that the analysis of the data was complicated by
      significant effects involving ordering of treatment occurring for eight of the
      variables (one from SF-36, two from the GHQ, SAI, Salivary Cortisol, Systolic BP
      and HR). However, there was a difference in the State Anxiety Inventory values
      between the treatments of the order of 1.092 units (95%CI 0.211-1.976) (p=0.016,
      Wilks lambda=0.885, df=1, 48) in favour of reflexology. Changes in salivary
      cortisol comparing levels pre 1st to post 6th session favoured reflexology (95%CI
      0.098-2.644) (p=0.037, Wilks lambda=0.912, df=1, 48). A significant difference
      was found in the way the treatments affected change in systolic blood pressure
      following sessions; this favoured progressive muscle relaxation training
      (p=0.002, Wilks lambda=0.812, df=1, 48). CONCLUSION: Positive effects of both
      treatments following sessions and over the 6 weeks of treatment are reported,
      with limited evidence of difference between the two treatments, complicated by
      ordering effects.

PMID- 19161950
TI  - A pilot study on using acupuncture and transcutaneous electrical nerve
      stimulation to treat chronic non-specific low back pain.
AB  - OBJECTIVE: The present study tests whether a combined treatment of acupuncture
      and transcutaneous electrical nerve stimulation (TENS) is more effective than
      acupuncture or TENS alone for treating chronic low back pain (LBP). METHODS:
      Thirty-two patients with chronic LBP were randomly allocated to four groups. The
      acupuncture group (ACP) received only acupuncture treatment at selected acupoints
      for low back pain; the TENS group (TENS) received only TENS treatment at pain
      areas; the acupuncture and TENS group (A&T) received both acupuncture and TENS
      treatments; the control group (CT) received topical poultice (only when
      necessary). Each group received specific weekly treatment five times during the
      study. Outcome measures were pain intensity in terms of visual analogue scale
      (VAS) and QOL of low back in terms of Roland-Morris Disability Questionnaire
      (RDQ). RESULTS: The ACP, TENS and A&T groups all reported lower VAS and RDQ
      scores. Significant reduction in pain intensity (P<0.008) and significant
      improvement in QOL (P<0.008) were shown in the A&T group. CONCLUSION: Combined
      acupuncture and TENS treatment is effective in pain relief and QOL of low back
      improvement for the sampled patients suffering from chronic LBP.

PMID- 19161951
TI  - Acupuncturist Stephanie Downey talks about Brighton's Dolphin House Children's
      Clinic: a natural therapy centre for children and their families.

PMID- 19161953
TI  - Biofield therapies: biophysical basis and biological regulations?
AB  - Complementary and alternative medicine (CAM) is increasingly popular in
      biomedical health care. One area of alternative medicine, biofield therapies,
      claims to manipulate individuals 'energy field' in order to enhance healing and
      wellbeing. This article reviews some recent studies addressing the
      characterization of endogenous energy fields and the way they affect the
      physiologic processes.

PMID- 19161952
TI  - The effects of vacuumic bracing system on the patellofemoral articulation in
      patients with patellofemoral pain syndrome.
AB  - Patellar bracing is a component of treatment of patellofemoral joint (PFJ)
      problems. A new vacuumic brace was designed by the researchers that act based on
      an external vacuuming suction. Ten patients were undertaken for the CT scan study
      at both 0 degrees and 30 degrees knee flexion immediately pre- and post-bracing.
      Also they examined clinically pre, post and 1 week after using the brace.
      Measurements of patellofemoral joint space width (PFJSW) and patellofemoral joint
      area (PFJA) showed that the application of the vacuumic brace is able to create a
      significant patellofemoral joint distraction at both knee angles. A significant
      reduction in visual analog scale (VAS) and increase in kujala patellofemoral
      score (KPS) was found in subjects after using the brace for 1 week. In
      conclusion, the results conveyed that application of the vacuumic brace is able
      to create a joint distraction and useful changes in VAS and KPS parameters.

PMID- 19161954
TI  - Knowledge of Florida nurses and dietitians regarding dietary supplements.
AB  - BACKGROUND: Health care professionals should exhibit competency about dietary
      supplements to support the high number of Americans taking these products.
      OBJECTIVES: To evaluate the knowledge of Florida nurses and dietitians regarding
      dietary supplements. METHODS: Florida nurses (n=600) and dietitians (n=600) were
      randomly selected to participate in a self-reported online survey. The actual
      knowledge of these professionals regarding nutrient-based and herbal supplements
      was evaluated by a quiz. RESULTS: Data of 89 dietitians and 64 nurses were
      analyzed using independent sample t-test and Pearson's correlation. The actual
      knowledge of both professionals revealed a mean correct score of 12.98+/-6.16
      (maximum score=30). Dietitians had a significantly greater knowledge of dietary
      supplements when compared to nurses (P=0.000). Both professionals were more
      knowledgeable on nutrient-based supplements than herbal. CONCLUSIONS: Both groups
      had a fairly low knowledge of side effects of dietary supplements and their
      interactions with common medications, and seem to require additional education in
      this area. Focused training can be designed to improve professionals' knowledge
      about dietary supplements.

PMID- 19161955
TI  - Rebuttal paper to 'Sunflower therapy for children with specific learning
      difficulties (dyslexia): a randomised, controlled trial'.

PMID- 19161956
TI  - Maintaining optimism despite a challenging social context.

PMID- 19161957
TI  - A comparison of second-degree baccalaureate and traditional-baccalaureate new
      graduate RNs: implications for the workforce.
AB  - The purpose of this study was to describe the differences between traditional
      baccalaureate graduates (TBGs) who had a baccalaureate degree in nursing and no
      other academic degree or diploma and second-degree baccalaureate graduates (SDGs)
      who had both a baccalaureate degree in nursing and a baccalaureate or higher
      degree in a field other than nursing. Using a sample of 953 newly licensed
      registered nurses (NLRNs), we compared SDGs and TBGs on demographic and work
      characteristics, including attitudes toward work, intent to stay in their current
      job, and whether they are searching for a job. TBGs worked slightly more hours
      per week and were more likely to provide direct care. SDGs were more likely to
      plan to stay indefinitely in their first job and were less uncertain of plans to
      stay. SDGs experienced higher family-work conflict and lower workgroup cohesion.
      Full-time SDGs earn over $2,700 more income per year. Potential explanations for
      the salary difference are the greater human capital that SDGs bring to the job
      and their older age. Understanding the workforce productivity of these two groups
      is important for both organizational planning and policy for recruitment and
      retention.

PMID- 19161958
TI  - Student satisfaction and team development outcomes with preassigned learning
      communities.
AB  - The purpose of this study was to determine if keeping baccalaureate nursing
      students together in the same learning community (LC)/clinical cohort throughout
      their entire clinical rotations (four semesters) was more or less helpful in
      fostering student satisfaction and team effectiveness. Using a model developed by
      the authors (Team Relationships with Clinical Cohorts Modell) and the Team
      Development Questionnaire by Payne (2001), there were no correlations between
      team effectiveness scores and the length of time the individuals in the LC were
      together. The only statistically significant finding when applied to nursing
      students is that as the fraction of females increased, the team effectiveness
      scores also increased (the team with the highest collective team score consisted
      of all white females with a narrow age range). Open-ended comments on positive
      aspects of staying with the same group included recurring themes of "friendship,"
      "support," and "a built-in study group;" although the longer the LC remained
      together, the more likely the students were to recommend changing LCs with each
      rotation. Given the diverse pool entering the nursing profession, educators must
      find a way to design clinical placements in the manner that best meets the needs
      of this rapidly changing student population.

PMID- 19161959
TI  - The impact of trait emotional intelligence on nursing team performance and
      cohesiveness.
AB  - Claims about the positive influence of emotional intelligence (EI) on work team
      performance are very numerous, both in commercial and scientific literature.
      However, despite the huge interest that media and business consultants put in EI
      and its fast-growing use in organizations, there is very little empirical
      evidence to support these claims. In this study, we investigated the
      relationships between EI, performance, and cohesiveness in 23 nursing teams. EI
      was assessed using the modified version of the Schutte Emotional Intelligence
      Scale and cohesiveness with the Group Cohesiveness Scale. Finally, nursing team
      performance was measured at four different levels: job satisfaction, chief
      nursing executives' rating, turnover rate, and health care quality. Results
      showed that health care quality was positively correlated with emotion
      regulation. Emotion regulation was also positively correlated with group
      cohesiveness. Surprisingly, it also appears that emotion appraisal was negatively
      correlated with the health care quality provided by teams. These results suggest
      that EI and, more specifically, Emotional Regulation may provide an interesting
      new way of enhancing nursing teams' cohesion and patient/client outcomes.

PMID- 19161960
TI  - Bringing nursing science to the classroom: a collaborative project.
AB  - This project resulted as a collaborative effort on the part of a public school
      system and nursing faculty. The fifth grade student population utilized in this
      study focused on the skeletal, muscular, digestive, circulatory, respiratory, and
      nervous systems as part of their school system's existing science and health
      curriculum. The intent of the study was to evaluate the impact on student
      learning outcomes as a result of nursing-focused, science-based, hands-on
      experiential activities provided by nursing faculty in the public school setting.
      An assessment tool was created for pretesting and posttesting to evaluate
      learning outcomes resulting from the intervention. Over a two day period, six
      classes consisting of 25 to 30 students each were divided into three equal small
      groups and rotated among three interactive stations. Students explored the normal
      function of the digestive system, heart, lungs, and skin. Improvement in learning
      using the pretest and posttest assessment tools were documented.

PMID- 19161961
TI  - Class size as related to the use of technology, educational practices, and
      outcomes in Web-based nursing courses.
AB  - With the expanding numbers of nursing students enrolled in Web-based courses and
      the shortage of faculty, class sizes are increasing. This exploratory descriptive
      study examined class size in relation to the use of technology and to particular
      educational practices and outcomes. The sample consisted of undergraduate (n =
      265) and graduate (n = 863) students enrolled in fully Web-based nursing courses.
      The Evaluating Educational Uses of Web-based Courses in Nursing survey (Billings,
      D., Connors, H., Skiba, D. (2001). Benchmarking best practices in Web-based
      nursing courses. Advances in Nursing Science, 23, 41--52) and the Social Presence
      Scale (Gunawardena, C. N., Zittle, F. J. (1997). Social presence as a predictor
      of satisfaction within a computer-mediated conferencing environment. The American
      Journal of Distance Education, 11, 9-26.) were used to gather data about the
      study variables. Class sizes were defined as very small (1 to 10 students), small
      (11 to 20 students), medium (21 to 30 students), large (31 to 40 students), and
      very large (41 students and above). Descriptive and inferential statistics were
      used to analyze the data. There were significant differences by class size in
      students' perceptions of active participation in learning, student-faculty
      interaction, peer interaction, and connectedness. Some differences by class size
      between undergraduate and graduate students were also found, and these require
      further study.

PMID- 19161962
TI  - Baccalaureate nursing students' information technology competence--agency
      perspectives.
AB  - Baccalaureate nurses must meet information technology (IT) competencies
      expectations for employment and future professional development. Unfortunately,
      educational programs and accrediting groups have not identified specific
      outcomes, and IT is not integrated formally into many undergraduate program
      curricula. Meanwhile, nursing students and faculty are practicing in clinical
      agencies undergoing an informatics and technology revolution. Adding courses and
      content, hardware, software, and strategies such as distance learning and
      simulation have been recommended to improve competency development. However,
      little is known regarding nursing students' experiences with IT in clinical
      practice. Agencies used as sites for one undergraduate program were surveyed and
      asked to identify barriers and facilitators to students' IT competencies
      attainment. Ten agency, program, and policy factors affecting the quality of the
      learning experience in clinical agencies were identified. Results underscored
      that leadership to improve collaboration and communication between nursing
      practice, education, and policy groups is necessary to improve clinical
      environments for IT learning.

PMID- 19161963
TI  - Integration of end-of-life care content in undergraduate nursing curricula:
      student knowledge and perceptions.
AB  - Studies indicate that nurses spend more time with patients at the end of life
      than any other health care discipline (K. M. Foley & H. Gelband, 2003). So it is
      imperative that nurses be educated so they can provide this high-quality end-of
      life care. The purpose of this project was to provide a current state of end-of
      life nursing education in the literature and to report on end-of-life knowledge
      and experiences of two groups of nursing students in one small, liberal arts
      university. A total of 111 undergraduate students (61 sophomores and 50 seniors)
      were administered a 50-item, multiple-choice test to determine their baseline
      knowledge about end-of-life care. Sophomore scores ranged from 20% to 86% with a
      mean of 60.98 (SD = 11.83). Senior pretest scores ranged from 70% to 96% with a
      mean of 83.26 (SD = 6.6). An independent samples t test was conducted to
      determine if there was a difference in group mean knowledge between sophomore and
      senior students. Levene's test for equality of variance was significant (F =
      4.22, P < .05); thus, a t test with equal variance assumed revealed a significant
      difference between sophomore and senior group means (t = -10.44, P < .001). The
      review of literature and student knowledge and experience assessment resulted in
      the development of a model of end-of-life curriculum integration implemented at
      the university and sets the stage for future program evaluation studies.

PMID- 19161964
TI  - Decentering resources: a phenomenological study of interpretive pedagogies in
      patient education.
AB  - The purpose of this interpretive phenomenological study was to document an
      innovative approach to teaching patient education where RN-Bachelor of Science in
      Nursing students, through an online course, learned and applied the interpretive
      pedagogies in patient education. The online course was the educational
      intervention which laid the groundwork of the study. Data were then collected
      from 9 of 18 students who took the course and agreed to participate. Interviews
      were audiotaped face to face or by telephone and transcribed and interpreted for
      meanings. Two themes that emerged for teaching patient education included
      "Decentering Resources: Listening Through Questioning" and "Decentering
      Resources: Empowering Through Questioning." This study revealed that, as students
      learned the interpretive pedagogies, resources (brochures, handouts, videos,
      etc.) took on less importance in their patient education practice. They
      recognized how resources frequently impeded patient-nurse interactions in
      teaching and learning encounters. Once students understood that they were perhaps
      depending too much on resources, they began engaging in questioning practices
      where significant meanings of listening and empowering in patient education
      unfolded. This study encourages nurse educators to teach students interpretive
      pedagogies in patient education to promote pedagogical literacy, which preserves
      the time-honored tradition of working together with patients during teaching and
      learning encounters.

PMID- 19161965
TI  - High efficacy of integrated preventive measures against zoonotic cutaneous
      leishmaniasis in northern Afghanistan, as revealed by Quantified Infection Rates.
AB  - Following an outbreak of more than 200 cases of zoonotic cutaneous leishmaniasis
      (ZCL) during 2004 and 2005 among International Security Assistance Force (ISAF)
      troops stationed in the Mazar-e Sharif (MeS) airport area, epidemiological
      investigations indicated the presence of a local high-density ZCL focus. Based on
      ZCL's specific transmission modes, density and seasonality, integrated preventive
      measures were continuously implemented from February 2006 at a German military
      camp constructed at MeS. Preventive techniques included such synergistic measures
      as skin repellents and insecticide-impregnated clothing, bednets and curtains,
      sand fly and rodent monitoring and control, extended habitat sanitation, and
      health education, all designed to achieve maximum protection against ZCL. Habitat
      alteration included: (a) erection of a 3.0m high stone wall around the entire
      camp area; (b) removal of > or =30cm of the upper earth layer throughout the
      site; (c) soil compaction and stone paving to a depth of > or =30cm plus
      compaction of the surrounding area to a distance of 100m outside the camp wall;
      and (d) regular eradication of vegetation. Aggressive implementation of these
      measures led to a 166-fold and 546-fold reduction in sand fly numbers and
      complete eradication of the local rodent reservoir, Rhombomys opimus, inside the
      camp during 2006 and 2007, respectively. ZCL attack rates decreased significantly
      (p<0.0001), from 17.5% (14 cases/80 persons) for the 2005 German assessment teams
      to 0.087% (1 case/1150 persons) for the 2006 contingent, and 0% (0 cases)
      (p<0.0001) for the 2007 contingent, with Quantified Infection Rates (QIRs) of
      0.058, 0.0000055, and 0.0, respectively. Using QIR values, the protective factor
      of the integrated preventive measures was shown to be > or =10,545 times higher
      in the 2006 and 2007 contingents, compared with the 2005 assessment teams.
      Results show that the continuously implemented, integrated preventive techniques
      used in this study gave excellent and long-lasting protection against zoonotic
      cutaneous leishmaniasis under field conditions.

PMID- 19161966
TI  - Neurocysticercosis immunodiagnosis using Taenia solium cysticerci crude soluble
      extract, excretory secretory and lower molecular mass antigens in serum and urine
      samples of Indian children.
AB  - Neurocysticercosis (NCC), the most common neurological disorder of parasite
      etiology, results from lodgement of Taenia solium cysticerci in the central
      nervous system and is now increasingly being recognized in children. The
      confirmed diagnosis is based collectively on radiological findings and
      serodiagnostic techniques. The serodiagnostic techniques have variable
      sensitivity and specificity depending upon the technique, antigens used, location
      and number of cysts. Crude soluble extract (CSE), excretory secretory (ES) and
      lower molecular mass (LMM) (10-30 kDa) antigenic fraction of T. solium cysticerci
      were evaluated for antibody detection in serum and urine samples by ELISA. Serum
      and urine samples were collected each from 125 clinically suspected and
      radiologically proven NCC (111 with single Computed Tomography (CT) lesions and
      14 with multiple CT lesions) and 125 control subjects (60 with neurological
      disorders other than NCC, 40 with other parasitic diseases and 25 apparently
      healthy subjects). The sensitivity of the ELISA with the use of CSE, ES and LMM
      antigenic fractions was 38.4%, 63.2% and 30.4% with serum (cut off dilution 400),
      46.4%, 44% and 47.2% with neat urine and the specificity was 88%, 76.8% and 85.6%
      with serum (cut off dilution 400), 66.4%, 65.2% and 58.4% with neat urine
      samples, respectively. The study suggests that detection of antibody to ES
      antigen in serum samples may serve useful purpose for the serodiagnosis of human
      NCC.

PMID- 19161967
TI  - Amino acid-selective isotope labeling of proteins for nuclear magnetic resonance
      study: proteins secreted by Brevibacillus choshinensis.
AB  - Here we report the first application of amino acid-type selective (AATS) isotope
      labeling of a recombinant protein secreted by Brevibacillus choshinensis for a
      nuclear magnetic resonance (NMR) study. To prepare the 15N-AATS-labeled protein,
      the transformed B. choshinensis was cultured in 15N-labeled amino acid-containing
      C.H.L. medium, which is commonly used in the Escherichia coli expression system.
      The analyses of the 1H-15N heteronuclear single quantum coherence (HSQC) spectra
      of the secreted proteins with a 15N-labeled amino acid demonstrated that alanine,
      arginine, asparagine, cysteine, glutamine, histidine, lysine, methionine, and
      valine are suitable for selective labeling, although acidic and aromatic amino
      acids are not suitable. The 15N labeling for glycine, isoleucine, leucine,
      serine, and threonine resulted in scrambling to specific amino acids. These
      results indicate that the B. choshinensis expression system is an alternative
      tool for AATS labeling of recombinant proteins, especially secretory proteins,
      for NMR analyses.

PMID- 19161968
TI  - Are genuine changes in protein expression being overlooked? Reassessing Western
      blotting.
AB  - This study used purified calsequestrin 1 and AMP kinase (AMPK) proteins to
      demonstrate how Western blotting outcomes can be influenced when either the
      density of proteins detected lie within a nonproportional region of a standard
      curve or a standard curve is not taken into account for data analyses. It
      outlines the likelihood of true changes being overlooked through the simple
      mistake of using band density alone and/or through analyzing too much sample. To
      demonstrate this, extrapolation of a typical linear, although nonproportional,
      standard curve resulted in approximately fourfold error. The standard curve
      method was used to estimate the concentration of AMPK beta1 in rat extensor
      digitorum longus muscle as being of the order of 60 microM. The article suggests
      that adopting a more sensitive Western blotting protocol will improve the
      reliability of quantitative Western blotting outcomes.

PMID- 19161970
TI  - A conserved hydrophobic core at Bcl-xL mediates its structural stability and
      binding affinity with BH3-domain peptide of pro-apoptotic protein.
AB  - Bcl-2 family proteins regulate apoptosis through their homo- and
      heterodimerization. By protein sequence analysis and structural comparison, we
      have identified a conserved hydrophobic core at the BH1 and BH2 domains of Bcl-2
      family proteins. The hydrophobic core is stabilized by hydrophobic interactions
      among the residues of Trp137, Ile140, Trp181, Ile182, Trp188 and Phe191 in Bcl
      x(L). Destabilization of the hydrophobic core can promote the protein unfolding
      and pore formation in synthetic lipid vesicles. Interestingly, though the
      hydrophobic core does not participate in binding with BH3 domain of pro-apoptotic
      proteins, disruption of the hydrophobic core can reduce the affinity of Bcl-x(L)
      with BH3-domain peptide by changing the conformation of Bcl-x(L) C-terminal
      residues that are involved in the peptide interaction. The BH3-domain peptide
      binding affinity and pore forming propensity of Bcl-x(L) were correlated to its
      death-repressor activity, which provides new information to help study the
      regulatory mechanism of anti-apoptotic proteins. Meanwhile, as the tryptophans
      are conserved in the hydrophobic core, in vitro binding assay based on FRET of
      "Trp-->AEDANS" can be devised to screen for new modulators targeting anti
      apoptotic proteins as well as "multi-BH domains" pro-apoptotic proteins.

PMID- 19161969
TI  - Combined use of mass spectrometry and heterologous expression for identification
      of membrane-interacting peptides in cytochrome P450 46A1 and NADPH-cytochrome
      P450 oxidoreductase.
AB  - Cytochrome P450 46A1 (CYP46A1) and NADPH-cytochrome P450 oxidoreductase (CPR) are
      the components of the brain microsomal mixed-function monooxygenase system that
      catalyzes the conversion of cholesterol to 24-hydroxycholesterol. Both CYP46A1
      and CPR are monotopic membrane proteins that are anchored to the endoplasmic
      reticulum via the N-terminal transmembrane domain. The exact mode of peripheral
      association of CYP46A1 and CPR with the membrane is unknown. Therefore, we
      studied their membrane topology by using an approach in which solution-exposed
      portion of heterologously expressed membrane-bound CYP46A1 or CPR was removed by
      digestion with either trypsin or chymotrypsin followed by extraction of the
      residual peptides and their identification by mass spectrometry. The identified
      putative membrane-interacting peptides were mapped onto available crystal
      structures of CYP46A1 and CPR and the proteins were positioned in the membrane
      considering spatial location of the missed cleavage sites located within these
      peptide as well as the flanking residues whose cleavage produced these peptides.
      Experiments were then carried out to validate the inference from our studies that
      the substrate, cholesterol, enters CYP46A1 from the membrane. As for CPR, its
      putative membrane topology indicates that the Q153R and R316W missense mutations
      found in patients with disordered steroidogenesis are located within the membrane
      associated regions. This information may provide insight in the deleterious
      nature of these mutations.

PMID- 19161971
TI  - Kinetic analysis of product release and metal ions in a metallonuclease.
AB  - Most nucleases rely on divalent cations as cofactors to catalyze the hydrolysis
      of nucleic acid phosphodiester bonds. Here both equilibrium and kinetic
      experiments are used to test recently proposed models regarding the metal ion
      dependence of product release and the degree of cooperativity between metal ions
      bound in the active sites of the homodimeric PvuII endonuclease. Equilibrium
      fluorescence anisotropy studies indicate that product binding is dramatically
      weakened in the presence of metal ions. Pre-steady state kinetics indicate that
      product release is at least partially rate limiting. Steady state and pre-steady
      state data fit best to models in which metals remain bound to the enzyme after
      the release of product. Finally, analysis of cooperative and independent binding
      models for metal ions indicates that single turnover kinetic data are consistent
      with little to no positive cooperativity between the two metal ions binding each
      active site.

PMID- 19161972
TI  - Evidence for a distinct ligand binding site on tubulin discovered through
      inhibition by GDP of paclitaxel-induced tubulin assembly in the absence of
      exogenous GTP.
AB  - GDP inhibits paclitaxel-induced tubulin assembly without GTP when the tubulin
      bears GDP in the exchangeable site (E-site). Initially, we thought inhibition was
      mediated through the E-site, since small amounts of GTP or Mg(2+), which favors
      GTP binding to the E-site, reduced inhibition by GDP. We thought trace GTP
      released from the nonexchangeable site (N-site) by tubulin denaturation was
      required for polymer nucleation, but microtubule length was unaffected by GDP.
      Further, enhancing polymer nucleation reduced inhibition by GDP. Other mechanisms
      involving the E-site were eliminated experimentally. Upon finding that ATP weakly
      inhibited paclitaxel-induced assembly, we concluded that another ligand binding
      site was responsible for these inhibitory effects, and we found that GDP was not
      binding at the taxoid, colchicine, or vinca sites. There may therefore be a lower
      affinity site on tubulin to which GDP can bind distinct from the E- and N-sites,
      possibly on alpha-tubulin, based on molecular modeling studies.

PMID- 19161973
TI  - mitoEnergetics and cancer cell fate.
AB  - The critical role of mitochondria in cell fate decisions has been well documented
      over the years. These observations have highlighted the way mitochondrial
      physiology controls cell survival and growth in the normal settings, the critical
      role of mitochondrial outer membrane permeabilization and altered mitoenergetics
      in cell death execution, and most importantly the association of altered
      mitochondrial metabolism with pathological states, in particular cancer.
      Reprogramming of cell metabolism, an invariable finding in cancer cells, is
      tightly linked to mitoenergetics as is evidenced by up-regulation of nutrient
      uptake and a pro-oxidant tilt in the intracellular milieu. The latter has also
      been demonstrated in oncogene-induced carcinogenesis models, notably as a
      functional outcome of Bcl-2 overexpression. Interestingly, even in that model,
      mitochondria appear to be the target as well. Thus the association of metabolic
      re-circuiting and altered mitoenergetics with the process of transformation has
      resulted in a paradigm shift in the way cancer development and progression is
      viewed today, which has tremendous implications for the development of novel and
      strategic therapeutic modalities.

PMID- 19161974
TI  - Ca(2+) binding to c-state of adenine nucleotide translocase (ANT)-surrounding
      cardiolipins enhances (ANT)-Cys(56) relative mobility: a computational-based
      mitochondrial permeability transition study.
AB  - The oxidation of critical cysteines/related thiols of adenine nucleotide
      translocase (ANT) is believed to be an important event of the Ca(2+)-induced
      mitochondrial permeability transition (MPT), a process mediated by a cyclosporine
      A/ADP-sensitive permeability transition pores (PTP) opening. We addressed the ANT
      Cys(56) relative mobility status resulting from the interaction of
      ANT/surrounding cardiolipins with Ca(2+) and/or ADP by means of computational
      chemistry analysis (Molecular Interaction Fields and Molecular Dynamics studies),
      supported by classic mitochondrial swelling assays. The following events were
      predicted: (i) Ca(2+) interacts preferentially with the ANT surrounding
      cardiolipins bound to the H4 helix of translocase, (ii) weakens the
      cardiolipins/ANT interactions and (iii) destabilizes the initial ANT-Cys(56)
      residue increasing its relative mobility. The binding of ADP that stabilizes the
      conformation "m" of ANT and/or cardiolipin, respectively to H5 and H4 helices,
      could stabilize their contacts with the short helix h56 that includes Cys(56),
      accounting for reducing its relative mobility. The results suggest that Ca(2+)
      binding to adenine nucleotide translocase (ANT)-surrounding cardiolipins in c
      state of the translocase enhances (ANT)-Cys(56) relative mobility and that this
      may constitute a potential critical step of Ca(2+)-induced PTP opening.

PMID- 19161976
TI  - Regulation of plasma membrane calcium fluxes by mitochondria.
AB  - The role of mitochondria in cell signaling is becoming increasingly apparent, to
      an extent that the signaling role of mitochondria appears to have stolen the
      spotlight from their primary function as energy producers. In this chapter, we
      will review the ionic basis of calcium handling by mitochondria and discuss the
      mechanisms that these organelles use to regulate the activity of plasma membrane
      calcium channels and transporters.

PMID- 19161977
TI  - Integrins during evolution: evolutionary trees and model organisms.
AB  - The integrins form a large family of cell adhesion receptors. All multicellular
      animals express integrins, indicating that the family evolved relatively early in
      the history of metazoans, and homologous sequences of the component domains of
      integrin alpha and beta subunits are seen in prokaryotes. Some integrins,
      however, seem to be much younger. For example, the alphaI domain containing
      integrins, including collagen receptors and leukocyte integrins, have been found
      in chordates only. Here, we will discuss what conclusions can be drawn about
      integrin function by studying the evolutionary conservation of integrins. We will
      also look at how studying integrins in organisms such as the fruit fly and mouse
      has helped our understanding of integrin evolution-function relationships. As an
      illustration of this, we will summarize the current understanding of integrin
      involvement in skeletal muscle formation.

PMID- 19161978
TI  - How does the Bax-alpha1 targeting sequence interact with mitochondrial membranes?
      The role of cardiolipin.
AB  - A key event in programmed cell death is the translocation of the apoptotic Bax
      protein from the cytosol towards mitochondria. The first helix localized at the N
      terminus of Bax (Bax-alpha1) can act here as an addressing sequence, which
      directs activated Bax towards the mitochondrial surface. Solid state NMR (nuclear
      magnetic resonance), CD (circular dichroism) and ATR (attenuated total
      reflection) spectroscopy were used to elucidate this recognition process of a
      mitochondrial membrane system by Bax-alpha1. Two potential target membranes were
      studied, with the outer mitochondrial membrane (OM) mimicked by neutral
      phospholipids, while mitochondrial contact sites (CS) contained additional
      anionic cardiolipin. (1)H and (31)P magic angle spinning (MAS) NMR revealed Bax
      alpha1 induced pronounced perturbations in the lipid headgroup region only in
      presence of cardiolipin. Bax-alpha1 could not insert into CS membranes but at
      elevated concentrations it inserted into the hydrophobic core of cardiolipin-free
      OM vesicles, thereby adopting beta-sheet-like features, as confirmed by ATR. CD
      studies revealed, that the cardiolipin mediated electrostatic locking of Bax
      alpha1 at the CS membrane surface promotes conformational changes into an alpha
      helical state; a process which seems to be necessary to induce further
      conformational transition events in activated Bax which finally causes
      irreversible membrane permeabilization during the mitochondrial apoptosis.

PMID- 19161975
TI  - Characteristics and possible functions of mitochondrial Ca(2+) transport
      mechanisms.
AB  - Mitochondria produce around 92% of the ATP used in the typical animal cell by
      oxidative phosphorylation using energy from their electrochemical proton
      gradient. Intramitochondrial free Ca(2+) concentration ([Ca(2+)](m)) has been
      found to be an important component of control of the rate of this ATP production.
      In addition, [Ca(2+)](m) also controls the opening of a large pore in the inner
      mitochondrial membrane, the permeability transition pore (PTP), which plays a
      role in mitochondrial control of programmed cell death or apoptosis. Therefore,
      [Ca(2+)](m) can control whether the cell has sufficient ATP to fulfill its
      functions and survive or is condemned to death. Ca(2+) is also one of the most
      important second messengers within the cytosol, signaling changes in cellular
      response through Ca(2+) pulses or transients. Mitochondria can also sequester
      Ca(2+) from these transients so as to modify the shape of Ca(2+) signaling
      transients or control their location within the cell. All of this is controlled
      by the action of four or five mitochondrial Ca(2+) transport mechanisms and the
      PTP. The characteristics of these mechanisms of Ca(2+) transport and a discussion
      of how they might function are described in this paper.

PMID- 19161979
TI  - Role of Cks1 amplification and overexpression in breast cancer.
AB  - Gain of chromosome 1q is a common event in many kinds of carcinomas. The Cks1
      gene, located at 1q21, is required for p27 ubiquitination by the SCF(skp2)
      ubiquitinating machinery. In the present study, we found that Cks1 gene
      amplification was highly correlated with protein overexpression. Statistical
      analysis showed that amplification and overexpression of Cks1 were strongly
      associated with lymph node metastasis and poor prognosis. At the molecular level,
      knockdown of Cks1 expression by RNA interference inhibited the growth of MDA-MB
      231 cells, damaged cell migration and invasion ability. Knockdown of Cks1
      expression promoted apoptosis of breast cancer cells and a wobble mutant of Cks1
      that was resistant to Cks1 siRNA can rescue this effect. Overexpression of Cks1
      inhibited the apoptosis of breast cancer cells through the MEK-Erk pathway. These
      data suggest that Cks1 is an oncogene in the 1q21 amplicon and plays an important
      role for breast cancer development.

PMID- 19161980
TI  - Development of mesenchymal stem cells partially originate from the neural crest.
AB  - Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal stem cells
      isolated from many adult tissues. Previous studies reported that MSCs can
      differentiate to both mesodermal and neural lineages by a phenomenon referred to
      as ''dedifferentiation'' or ''transdifferentiation''. However, since MSCs have
      only been defined in vitro, much of their development in vivo is still unknown.
      Here, we prospectively identified MSCs in the bone marrow from adult transgenic
      mice encoding neural crest-specific P0-Cre/Floxed-EGFP and Wnt1-Cre/Floxed-EGFP.
      EGFP-positive MSCs formed spheres that expressed neural crest stem cell genes and
      differentiated into neurons, glial cells, and myofibroblasts. Interestingly, we
      observed MSCs both in the GFP(+) and GFP(-) fraction and found that there were no
      significant differences in the in vitro characteristics between these two
      populations. Our results suggest that MSCs in adult bone marrow have at least two
      developmental origins, one of which is the neural crest.

PMID- 19161982
TI  - The N-terminal half of the receptor domain of botulinum neurotoxin A binds to
      microdomains of the plasma membrane.
AB  - Botulinum neurotoxin type A (BoNT/A) is largely employed in human therapy because
      of its specific inhibition of peripheral cholinergic nerve terminals. BoNT/A
      binds to them rapidly and with high specificity via its receptor binding domain
      termed HC. Recent evidence indicate that BoNT/A interacts specifically with
      polysialogangliosides and with a luminal loop of the synaptic vesicle protein SV2
      via the C-terminal half of HC. Here we show that the N-terminal half of HC binds
      to sphingomyelin-enriched membrane microdomains and that it has a defined
      interaction with phosphatidylinositol phosphates (PIP). We have identified a PIP
      binding site in this half of HC and we show how this interaction could predispose
      BoNT/A for membrane insertion, which is the step subsequent to binding, in the
      four-steps route leading BoNT/A inside nerve terminals.

PMID- 19161981
TI  - N114S mutation causes loss of ATP-induced aggregation of human
      phosphoribosylpyrophosphate synthetase 1.
AB  - This study examined recombinant wild-type human phosphoribosylpyrophosphate
      synthetase 1 (wt-PRS1, EC 2.7.6.1) and the point mutant Asn114Ser PRS1 (N114S
      Mutant) in cells of a patient with primary gout. Dynamic light-scattering and
      sedimentation velocity experiments indicated that the monomeric wt-PRS1 in
      solution was assembled into hexamers after adding the substrate ATP. However,
      this ATP-induced aggregation effect was not observed with N114S-Mutant, which has
      a 50% higher enzymatic activity than that of wt-PRS1. Synchrotron radiation
      circular dichroism spectroscopy revealed that the point mutation causes an
      increase of alpha-helix content and a decrease of turn content. Examination of
      the crystal structure of wt-PRS1 indicated that 12 hydrogen bonds formed by 6
      pairs of N114 and D139 have an important role in stabilizing the hexamer. We
      suggest that the substitution of S114 for N114 in N114S-Mutant leads to the
      rupture of 12 hydrogen bonds and breakage of the PO43- allosteric site where PO43
      functions as a fixer of the ATP-binding loop. Therefore, we consider that
      formation of the hexamer as the structural basis of the ADP allosteric inhibition
      is greatly weakened by the N114S mutation, and that alteration of the ATP-binding
      loop conformation is the key factor in the increased activity of N114S-Mutant.
      These two factors could be responsible for the high level of activity of N114S
      Mutant in this patient.

PMID- 19161983
TI  - Candesartan attenuates Angiotensin II-induced mesangial cell apoptosis via
      TLR4/MyD88 pathway.
AB  - Angiotensin II (Ang II) can stimulate Toll-like receptor 4 (TLR4) expression in
      mesangial cells (MCs), but the role of TLR4 in the Ang II-induced apoptosis and
      the effect of candesartan on TLR4 expression remain unclear. Here, we report that
      Ang II-induced MC apoptosis in a time-dependent manner and up-regulated
      TLR4/MyD88 expression, and that the intracellular ROS was subsequently increased.
      We also show that candesartan attenuated the Ang II-induced MC apoptosis, and
      that this protective effect was dependent on decreased TLR4/MyD88 expression as
      well as reduced intracellular ROS formation. Furthermore, Ang II increased the
      apoptosis inducing factor protein level, while candesartan markedly reduced this
      increase. These results demonstrate that TLR4/MyD88 pathway was involved in the
      Ang II promoted MC apoptosis, which was related to TLR4/MyD88 mediated oxidative
      stress. These data also suggest that candesartan exerted anti-apoptotic effect as
      an antioxidant by modulating this pathway.

PMID- 19161984
TI  - p21 functions in a post-mitotic block checkpoint in the apoptotic response to
      vinblastine.
AB  - We have shown previously that in KB-3 (HeLa) cells vinblastine causes
      downregulation of the CDK inhibitor p21 through a c-Jun regulated pathway. To
      test the hypothesis that p21 downregulation is necessary to alleviate a
      protective function, we transfected p21 in KB-3 cells and examined the apoptotic
      response to vinblastine. The results showed that cells overexpressing p21 were
      apoptosis-resistant, not through an ability of p21 to cause cell cycle arrest
      prior to mitotic arrest, but through altering the fate of mitotically arrested
      cells after drug treatment. Moreover, p21 null HCT116 cells were more prone to
      vinblastine-induced apoptosis relative to wild-type cells. The results provide
      support for a model whereby p21 downregulation promotes vinblastine-induced
      apoptosis by alleviating its protective function following mitotic arrest.

PMID- 19161985
TI  - A role for SOX2 in the generation of microtubule-associated protein 2-positive
      cells from microglia.
AB  - We recently demonstrated that, as a type of multipotential stem cells, microglia
      give rise to microtubule-associated protein 2 (MAP2)-positive and glial
      fibrillary acidic protein (GFAP)-positive cells. In this study, we investigated
      the role of SOX2, a high-mobility group DNA binding domain transcription factor,
      in the generation of microglia-derived MAP2-positive and GFAP-positive cells.
      Western blot analysis demonstrated that expression of SOX2 was upregulated by
      treatment with 70% fetal bovine serum treatment. Immunocytochemical analyses
      demonstrated that SOX2 expression was evident in the nuclei of microglia-derived
      MAP2-positive and GFAP-positive cells, whereas it was not present in the nuclei
      of microglia. These assays also showed that Sox2 siRNA inhibited the generation
      of MAP2-positive and GFAP-positive cells from microglia. Interestingly, this
      activity was also inhibited by Smad4 siRNA, which reduces SOX2 expression. These
      results indicate that SOX2 upregulation is involved in the generation of
      microglia-derived MAP2-positive and GFAP-positive cells through SMAD4.

PMID- 19161986
TI  - The AMD3100 story: the path to the discovery of a stem cell mobilizer (Mozobil).
AB  - AMD3100 was found to inhibit HIV-1 and HIV-2 within the 1-10nM concentration
      range while not being toxic to the host cells at concentrations up to 500 microM,
      thus achieving a selectivity index of approximately 100,000. The target of action
      was initially thought to be the viral envelope glycoprotein gp120. It appeared
      only to be the indirect target. The direct target of action turned out to be the
      co-receptor CXCR4 used by T-lymphotropic HIV strains (now referred to as X4
      strains) to enter the cells. Initial (phase I) clinical trials undertaken with
      AMD3100, as a prelude to its development as a candidate anti-HIV drug for the
      treatment of AIDS, showed an unexpected side effect: an increase in the white
      blood cell counts. Apparently, AMD3100 specifically increased CD34+ hematopoietic
      stem cell counts in the peripheral blood. Stromal derived factor 1 (SDF-1),
      through its interaction with CXCR4, retains the stem cells in the bone marrow (a
      process referred to as "homing"), and AMD3100 specifically antagonizes this
      interaction. AMD3100 in combination with granulocyte colony-stimulating factor (G
      CSF) resulted in the collection of more progenitor cells than G-CSF alone. At
      present, the major indication for clinical use of AMD3100 (Mozobil) is the
      mobilization of hematopoietic stem cells from the bone marrow into the
      circulating blood for transplantation in patients with hematological malignancies
      such as non-Hodgkin's lymphoma or multiple myeloma.

PMID- 19161987
TI  - Ready for a comeback of natural products in oncology.
AB  - Since the late 1990s and the rapid expansion of monoclonal antibodies and
      synthetic protein kinase inhibitors in oncology, anticancer natural products fell
      out of fashion with the pharmaceutical industry. But in 2007 with the approval of
      three new drugs derived from natural products, the emergence of promising
      antitumor compounds from microorganisms (e.g. alvespimycin, salinosporamide) and
      the growing importance of new formulations of known natural product-derived drugs
      (nanoparticle formulations, oral forms), we are witnessing a new wave for natural
      products in oncology. The recent approval of the microtubule-targeted epothilone
      derivative ixabepilone (Ixempra), the DNA-alkylating marine alkaloid trabectedin
      (Yondelis) and the inhibitor of mTOR protein kinase temsirolimus (Torisel) is
      emblematic of the evolution of the field which combines the long established
      finding of conventional cytotoxic agents and the emergence of molecularly
      targeted therapeutics. These three examples also illustrate the increasing
      importance of microbial sources for the discovery of medically useful natural
      products. The contribution of innovative biological targets is also highlighted
      here, with references to proteasome inhibitors and novel approaches such as
      manipulation of mRNA splicing. Altogether, these observations plead for the
      return of natural products in oncology.

PMID- 19161988
TI  - The NF kappa B-mediated control of RS and JNK signaling in vitamin A-treated
      cells: duration of JNK-AP-1 pathway activation may determine cell death or
      proliferation.
AB  - Nuclear factor kappa B (NFkappaB) has emerged as a crucial regulator of cell
      survival, playing important functions in cellular resistance to oxidants and
      chemotherapeutic agents. Recent studies showed that NFkappaB mediates cell
      survival through suppression of the accumulation of reactive species (RS) and a
      control of sustained activation of the Jun-N-terminal kinase (JNK) cascade. This
      work was undertaken in order to evaluate the role of NFkappaB in modulating the
      pro-oxidant effects of supplementation with vitamin A (retinol, ROH) in Sertoli
      cells, a major ROH physiological target. In this work, we reported that ROH
      treatment increases mitochondrial RS formation leading to a redox-dependent
      activation of NFkappaB. NFkappaB activation played a pivotal role in counteract
      RS accumulation in ROH-treated cells, since NFkappaB inhibition with DNA decoy
      oligonucleotides or pharmacological inhibitors (BAY-117082) potentiated ROH
      induced RS accumulation and oxidative damage. In the presence of NFkappaB
      inhibition, ROH-induced oxidative stress promoted a prolonged activation of the
      JNK-activator protein 1 (AP-1) pathway and induced significant decreases in cell
      viability. Inhibition of JNK-AP-1 with decoy oligonucleotides to AP-1 or JNK
      inhibitor SP600125 prevented the decreases in cell viability. Antioxidants
      blocked the persistent JNK-AP-1 activation, cell oxidative damage, and the
      decreases in cell viability induced by NFkappaB inhibition. Finally, our data
      point superoxide dismutase (SOD)2 as a potential antioxidant factor involved in
      NFkappaB protective effects against ROH-induced oxidative stress. Taken together,
      data presented here show that NFkappaB mediates cellular resistance to the pro
      oxidant effects of vitamin A by inhibiting RS accumulation and the persistent and
      redox-dependent activation of JNK-AP-1 cascade.

PMID- 19161989
TI  - Curcumin-induced degradation of PKC delta is associated with enhanced dentate
      NCAM PSA expression and spatial learning in adult and aged Wistar rats.
AB  - Polysialylation of the neural cell adhesion molecule (NCAM PSA) is necessary for
      the consolidation processes of hippocampus-based learning. Previously, we have
      found inhibition of protein kinase C delta (PKCdelta) to be associated with
      increased polysialyltransferase (PST) activity, suggesting inhibitors of this
      kinase might ameliorate cognitive deficits. Using a rottlerin template, a drug
      previously considered an inhibitor of PKCdelta, we searched the Compounds
      Available for Purchase (CAP) database with the Accelrys((R)) Catalyst programme
      for structurally similar molecules and, using the available crystal structure of
      the phorbol-binding domain of PKCdelta, found that diferuloylmethane (curcumin)
      docked effectively into the phorbol site. Curcumin increased NCAM PSA expression
      in cultured neuro-2A neuroblastoma cells and this was inversely related to
      PKCdelta protein expression. Curcumin did not directly inhibit PKCdelta activity
      but formed a tight complex with the enzyme. With increasing doses of curcumin,
      the Tyr(131) residue of PKCdelta, which is known to direct its degradation,
      became progressively phosphorylated and this was associated with numerous
      Tyr(131)-phospho-PKCdelta fragments. Chronic administration of curcumin in vivo
      also increased the frequency of polysialylated cells in the dentate infragranular
      zone and significantly improved the acquisition and consolidation of a water maze
      spatial learning paradigm in both adult and aged cohorts of Wistar rats. These
      results further confirm the role of PKCdelta in regulating PST and NCAM PSA
      expression and provide evidence that drug modulation of this system enhances the
      process of memory consolidation.

PMID- 19161990
TI  - Aspirin and indomethacin reduce lung inflammation of mice exposed to cigarette
      smoke.
AB  - Neutrophil accumulation response to cigarette smoke (CS) in humans and animal
      models is believed to play an important role in pathogenesis of many tobacco
      related lung diseases. Here we evaluated the lung anti-inflammatory effect of
      aspirin and indomethacin in mice exposed to CS. C57BL/6 mice were exposed to four
      cigarettes per day during 4 days and were treated i.p. with aspirin or
      indomethacin, administered each day 1h before CS exposure. Twenty four hours
      after the last exposure, cells and inflammatory mediators were assessed in
      bronchoalveolar lavage (BAL) fluid and the lungs used for evaluation of lipid
      peroxidation, p38 mitogen-activated protein kinase (MAPK) phosphorylation and
      nuclear transcription factor kappaB (NF-kappaB) activation. Exposure to CS
      resulted in a marked lung neutrophilia. Moreover, the levels of oxidative stress
      related lipid peroxidation, prostaglandin E(2) (PGE(2)), interleukin 1beta (IL
      1beta), monocyte chemotactic protein 1 (MCP-1), and activated NF-kappaB and p38
      MAPK were greatly increased in CS group. Aspirin or indomethacin treatment led to
      a significant reduction of neutrophil influx, but only aspirin resulted in
      dramatic decrease of inflammatory mediators. Moreover, both drugs reduced lung
      p38 MAPK and NF-kappaB activation induced by CS. These results demonstrate that
      short-term CS exposure has profound airway inflammatory effects counteracted by
      the anti-inflammatory agents aspirin and indomethacin, probably through COX
      dependent and -independent mechanisms.

PMID- 19161991
TI  - Pentoxifylline treatment improves neurological and neurochemical deficits in rats
      subjected to transient brain ischemia.
AB  - The possible neuroprotector effects of pentoxifylline (P), a methylxanthine
      derivative and phosphodiesterase inhibitor, were studied on male Wistar rats
      subjected to a model of transient brain ischemia. One group was treated, 1 h
      before ischemia (ISC) and 1 h after, with pentoxifylline (P), 50 and 100 mg/kg,
      i.p. (ISC+P). The other groups were ischemic, ISC; sham operated, SO; P100;
      SO+P100; and normal controls, N. One week after ischemia, the animals were
      submitted to the open field, passive avoidance, and water maze tests for
      evaluating locomotor activity and cognitive deficits, as well as for
      scintillographic (SPECT) measurements. After these procedures, they were
      sacrificed and their brain dissected under ice, for histological studies as well
      as striatal dopamine (DA) and DOPAC measurements by HPLC. In the open field test,
      ischemia increased locomotor activity, as compared to N, SO, P100 and SO+P100.
      This parameter was not significantly reversed after P treatment (ISC+P50 or
      ISC+P100). Grooming behavior was also increased in the ISC group, as compared to
      all other ones, although only statistically different as compared to the P100
      group. The P treatment (ISC+P50 and ISC+P100) brought these values close to
      normality. In the passive avoidance test, ischemia significantly impaired the
      short term memory, as compared to the N group, as well as scopolamine (SCP) used
      as a positive control. In the long term memory, similar effects were observed in
      the ISC and SCP groups that significantly impaired memory consolidation. P
      treatment completely reversed the effects observed after ischemia (ISC+P50 and
      ISC+P100) on the short as well as on the long term memory, and values were
      similar to those of the P100 group (which increased both parameters, as related
      to the N group). In the water maze, the ISC group was not different from the N,
      SO and SO+P100 groups. However, ISC+P50, ISC+P100 and P100 significantly improved
      the spatial memory, as related to all other groups. SPECT data showed that
      ischemia produced a lower but significant decrease in brain optical densities,
      and P brought values close to those seen in the N group. Furthermore, P treatment
      of the ischemic group (ISC+P50) increased the number of viable hippocampal CA3
      neurons, as compared to the ISC group. While ischemia significantly decreased DA
      levels, the P treatment of ischemic animals brought those values close to
      normality. In conclusion, P counteracted neurological and neurochemical changes
      seen after brain ischemia, in rats. The TNF-alpha inhibition and anti
      inflammatory actions of P could be responsible, at least in part, for the
      neuroprotection afforded by the drug.

PMID- 19161992
TI  - Increased c-fos immunoreactivity in the spinal cord and brain following spinal
      cord stimulation is frequency-dependent.
AB  - Spinal cord stimulation (SCS) is an alternative approach for treatment of
      neuropathic pain when conservative management is ineffective. Previously we
      showed both 4 Hz and 60 Hz SCS reduces hyperalgesia in an animal model of
      neuropathic pain. However, the mechanisms underlying the pain reduction by SCS
      and how different frequencies of SCS produce the analgesic effect are unclear. To
      elucidate potential sites modulated by SCS we examined distribution of c-fos in
      Sprague-Dawley rats with spared nerve injury (SNI) and those without injury in
      response to SCS. SCS was delivered at one of 3 different frequencies (4 Hz, 60
      Hz, and 100 Hz) for 30 min 2 weeks after SNI or in animals without SNI. Animals
      were perfused either 5 min or 2 h after SCS and c-fos protein examined
      immunohistochemically. The number of c-fos positive cells significantly increased
      5 min (35 min after SCS began) after 4 Hz SCS in the NRM, but not PAG in animals
      with nerve injury. The number of c-fos positive cells was significantly increased
      bilaterally 2 h after either 4 Hz or 60 Hz SCS in the spinal cord dorsal horn in
      the cervical enlargement and under the electrode, but not in the lumbar
      enlargement in animals with nerve injury. In uninjured animals 4 Hz SCS increased
      c-fos expression at the electrode site and lumbar enlargement when compared to
      animals implanted with the electrode who did not receive SCS. 100 Hz SCS had no
      effect on c-fos expression. Thus, at the time points examined in this model, low
      frequency SCS likely activates supraspinal and spinal mechanisms to produce
      analgesia, while higher frequencies activate spinal mechanisms.

PMID- 19161993
TI  - Perillyl alcohol attenuates Ras-ERK signaling to inhibit murine skin inflammation
      and tumorigenesis.
AB  - In the present study, the chemopreventive effect of topical application of
      perillyl alcohol (POH) on 9,10-dimethylbenz(a)anthracene (DMBA)-initiated and 12
      O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumorigenesis and its
      possible mechanisms of action in Swiss albino mice were investigated. We
      evaluated the effect of pretreatment of POH (6 and 12 mg/kg body weight) on TPA
      (2 microg/200 microl of acetone)-induced skin edema, hyperplasia, peroxidase
      damage and modulation in activities of catalase, glutathione reductase,
      glutathione peroxidase, glutathione-S-transferase and reduced glutathione
      contents. Application of POH 30 min prior to TPA treatment, showed a protective
      effect in almost all the investigated parameters. Additionally, pretreatment with
      POH showed a significant inhibition of ornithine decarboxylase (ODC) activity and
      [(3)H] thymidine incorporation into epidermal DNA. In promotion phase, a
      significant reduction was found in tumor incidence and tumor burden in mice
      pretreated with POH (12 mg/kg body weight) with extension of the latency period
      from 4 to 8 weeks as compared to those treated with TPA alone. POH significantly
      suppressed the Ras/Raf/ERK pathway and induced apoptosis in Swiss albino mice
      skin. Our findings suggested that the chemopreventive efficacy of POH is probably
      due to the inhibition of oxidative stress responses, inhibition of the Ras cell
      proliferation pathway and induction of apoptosis in murine skin tumor promotion
      phase.

PMID- 19161994
TI  - The free fatty acid metabolome in cerebral ischemia following human mesenchymal
      stem cell transplantation in rats.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have the potential to promote brain
      repair and improve recovery following stroke. We investigated changes in free
      fatty acids (FFAs) following intravenous human MSC (hMSC) transplantation into
      rats that had undergone transient middle cerebral artery occlusion (MCAo).
      METHODS: Rats were subjected to 2-hours MCAo, followed by intravenous
      transplantation of hMSC or phosphate-buffered saline (PBS) at one day after MCAo.
      All rats were sacrificed 5 days after MCAo. Metabolic profiling of free fatty
      acids (FFAs) level was assessed in plasma and brain from control rats (n=8), PBS
      treated MCAo rats (n=6), and hMSC-treated MCAo rats (MCAo+hMSC, n=6). RESULTS:
      The levels of some FFAs in plasma and brain samples of the MCAo and MCAo+hMSC
      groups were significantly different from those of the control group. The
      percentage composition of myristic acid in plasma and those of myristic acid,
      linoleic acid, and eicosenoic acid in brain tissues of the MCAo+hMSC group were
      significantly reduced compared to those in the untransplanted MCAo group.
      CONCLUSION: Our metabolic approach has provided insights into understanding the
      complexity of biochemical and physiological events that occur in ischemic brain
      injury and the transplantation effects of MSCs in stroke.

PMID- 19161995
TI  - Simultaneous genotyping of 11 non-synonymous SNPs in the 4 glutathione peroxidase
      genes using the multiplex single base extension method.
AB  - BACKGROUND: Glutathione peroxidase (Gpx) is one of the major antioxidant enzymes
      involved in scavenging hydrogen peroxide and lipid hydroperoxides produced during
      normal metabolism or after oxidative insult. In the Gpx genes, a number of single
      nucleotide polymorphisms (SNPs) have been identified and their associations with
      various diseases have been reported. In the present study, we used a multiplex
      single base extension (MSBE) technique to genotype multiple non-synonymous SNPs
      in the Gpx1, Gpx2, Gpx3 and Gpx4 genes simultaneously. METHODS: Seven templates
      for the MSBE reaction, involving 11 SNPs corresponding to non-synonymous
      mutations were amplified by multiplex PCR. Availability of the MSBE method was
      validated by genotyping DNA from 91 Japanese, 91 German and 93 Xhosa healthy
      subjects. RESULTS: A simple and reproducible method for simultaneous genotyping
      of multiple SNPs in the Gpx genes was established. Of the 11 SNPs, only Gpx1
      P200L was polymorphic in all three ethnic groups and the genotype distributions
      differed significantly among the three populations. On the other hand, little
      heterogeneity was observed for Gpx2 R146C, Gpx2 P126L, Gpx1 A194T and Gpx4 S2N,
      and no heterogeneity was observed for Gpx1 L6P, Gpx1 R5P, Gpx3 F128L, Gpx3 K144X,
      Gpx4 A88V and Gpx4 S227L. CONCLUSION: The MSBE procedure described here was
      proven to be applicable for population studies. Application of this method will
      provide comprehensive information for studying the relationship between SNPs in
      the Gpx genes and risks for various diseases.

PMID- 19161996
TI  - Assessment of DNA contamination from dried blood spots and determination of DNA
      yield and function using archival newborn dried blood spots.
AB  - BACKGROUND: Residual dried blood spots (DBS) from newborn screening programs are
      often stored for years and are sometimes used for epidemiological studies.
      Because there is potential for DNA cross-contamination from specimen-to-specimen
      contact, we determined contamination levels following intentional contact and
      assessed archival DBS DNA degradation after storage in an uncontrolled
      environment. METHODS: DBS from healthy adult females were rubbed with DBS from
      healthy or cystic fibrosis (CF)-affected adult males. Total human and male DNA
      was measured from the female DBS. Contamination levels were assessed using short
      tandem repeats (STRs). Female DBS contaminated with CF male DNA containing the
      F508del were analyzed for presence of this mutation. Archival DBS DNA
      amplification efficiency was determined using STR analysis. RESULTS: Most female
      DBS were contaminated, however only one specimen showed an incomplete STR profile
      consistent with contaminating CF-affected male DNA. Further testing by CF
      mutation screening was negative. DNA extracted from archival DBS showed robust
      amplification (range 100 bp-320 bp). CONCLUSIONS: Lightly abrasive contact
      between DBS resulted in DNA cross-contamination. The contaminating DNA did not
      interfere in CF-mutation tests; however this should be determined for individual
      assays. Since DNA from archival DBS robustly amplifies, newborn DBS could provide
      an invaluable resource for public health studies.

PMID- 19161997
TI  - A multiplex real-time PCR method for detection of GSTM1 and GSTT1 copy numbers.
AB  - OBJECTIVES: Deletion polymorphisms of Glutathione-S-transferase (GST) M1 and T1
      are considered risk factors for various diseases. However, most previous studies
      only distinguished "null" and "non-null" genotypes. Our aim was to develop a
      reliable, high-throughput GSTM1/T1 genotyping method able to determine allele
      copy numbers. DESIGN AND METHODS: We developed a multiplex real time PCR method
      to distinguish between heterozygous (1/0) and homozygous (1/1) GSTM1 and GSTT1
      genotypes. The principle of relative quantification was applied and an
      expectation-maximisation (EM) algorithm was developed to assign one of 3 possible
      genotypes: 1/1, 1/0 or 0/0 for each of the two genes. RESULTS: 1320 Caucasians
      were genotyped using the newly developed method. The observed genotype
      distributions did not deviate from the expected and were in Hardy-Weinberg
      equilibrium. GSTM1 duplication was detected in one sample. CONCLUSION: This new
      semiquantitative genotyping method is a sensitive and promising tool for large
      scale molecular epidemiological and clinical studies.

PMID- 19161998
TI  - Presence of high-molecular-weight forms and domain alterations of fibronectin in
      pleural effusion of patients with lung cancer.
AB  - OBJECTIVES: Appearance of fibronectin (FN) molecular forms and alterations of
      domain expositions can be associated with lung cancer. DESIGN AND METHODS: The
      presence of the FN molecular forms and epitopes in its cell-binding, carboxyl-,
      and amino-terminal domains was determined in the plasma and pleural effusion of
      patients suffering from small- and non-small-cell lung cancer, and lung
      inflammation by immunoblotting and FN-ELISA. RESULTS: The 320-kDa and 280-kDa FN
      forms as well as FN fragments appeared in the pleural effusion and plasma of
      patients suffering from lung inflammation or cancer in significantly higher
      relative amounts in both lung cancer groups than in the inflammation. The domain
      concentrations were higher in the cancer and inflammatory plasma groups than
      those in the control group. The higher N-terminal epitope expression in pleural
      effusion than in plasma indicates different epitope accessibility for the
      monoclonal antibody. CONCLUSIONS: The molecular status of FN probably reflects
      the dynamic changes which occur in cancer and inflammatory tissue.

PMID- 19161999
TI  - Determination of the water permeability (Lp) of mouse oocytes at -25 degrees C
      and its activation energy at subzero temperatures.
AB  - Typically, subzero permeability measurements are experimentally difficult and
      infrequently reported. Here we report an approach we have applied to mouse
      oocytes. Interrupted cooling involves rapidly cooling oocytes (50 degrees C/min)
      to an intermediate temperature above the intracellular nucleation zone, holding
      them for up to 40 min while they dehydrate, and then rapidly cooling them to -70
      degrees C or below. If the intermediate holding temperature and holding time are
      well chosen, high post thaw survival of the oocytes is possible because the
      freezable water is removed during the hold. The length of time required for the
      exit of the freezable water allows the water permeability at that temperature to
      be determined. These experiments used 1.5M ethylene glycol in PBS and included a
      transient hold of 2 min for equilibration at -10 degrees C, just below the
      extracellar ice formation temperature. We obtain an Lp=1.8 x 10(-3)microm min(
      1)atm(-1) at -25 degrees C based on a hold time of 30 min yielding 80% survival
      and the premise that most of the freezable water is removed during the 30 min
      hold. If we assume that the water permeability is a continuous function of
      temperature and that its Ea changes at 0 degrees C, we obtain a subzero Ea of 21
      kcal/mol; higher than the suprazero value of 14 kcal/mol. A number of assumptions
      are required for these water loss calculations and the resulting value of Lp can
      vary by up to a factor of 2, depending on the choices make.

PMID- 19162000
TI  - An experimental research on cryopreserving rabbit trachea by vitrification.
AB  - Vitrification is a promising alternative to tissue preservation, in which the
      tissue is permeated with cryoprotective agents (CPAs) in order to circumvent the
      hazardous effects associated with ice formation. In this study, we evaluate the
      effect of vitreous cryopreservation of rabbit trachea, by comparing vitrification
      procedure with conventional computer-programmed slow freezing approaches.
      Harvested rabbit trachea were tailored and divided into groups and cryopreserved
      by vitrification and programmed freezing, respectively. The morphology and
      ultrastructure of the thawed tracheal fragments including HE dyes, terminal
      deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL)
      staining, transmission electron microscopy (TEM) and scanning electron microscopy
      (SEM) were studied to assess the integrity of the tracheal fragments.
      Morphological studies demonstrated that both cryopreservation procedure retained
      the integrity of trachea, both epithelial cells, cilia and cartilage cells were
      in good shape. Compared with slow freezing methods, vitrification was less
      detrimental to cartilage cells and had a higher survival rate of chondrocytes and
      coverage of epithelium and cilia. Therefore, vitrification procedure can be a
      more satisfactory method to preserve trachea and the survival of chondrocytes in
      situ in cartilage tissue is adequate and respiratory epithelium is soundly
      present.

PMID- 19162001
TI  - Centrosome attachment to the C. elegans male pronucleus is dependent on the
      surface area of the nuclear envelope.
AB  - A close association must be maintained between the male pronucleus and the
      centrosomes during pronuclear migration. In C. elegans, simultaneous depletion of
      inner nuclear membrane LEM proteins EMR-1 and LEM-2, depletion of the nuclear
      lamina proteins LMN-1 or BAF-1, or the depletion of nuclear import components
      leads to embryonic lethality with small pronuclei. Here, a novel centrosome
      detachment phenotype in C. elegans zygotes is described. Zygotes with defects in
      the nuclear envelope had small pronuclei with a single centrosome detached from
      the male pronucleus. ZYG-12, SUN-1, and LIS-1, which function at the nuclear
      envelope with dynein to attach centrosomes, were observed at normal
      concentrations on the nuclear envelope of pronuclei with detached centrosomes.
      Analysis of time-lapse images showed that as mutant pronuclei grew in surface
      area, they captured detached centrosomes. Larger tetraploid or smaller
      histone::mCherry pronuclei suppressed or enhanced the centrosome detachment
      phenotype respectively. In embryos fertilized with anucleated sperm, only one
      centrosome was captured by small female pronuclei, suggesting the mechanism of
      capture is dependent on the surface area of the outer nuclear membrane available
      to interact with aster microtubules. We propose that the limiting factor for
      centrosome attachment to the surface of abnormally small pronuclei is dynein.

PMID- 19162003
TI  - Heart and craniofacial muscle development: a new developmental theme of distinct
      myogenic fields.
AB  - Head muscle development has been studied less intensively than myogenesis in the
      trunk, although this situation is gradually changing, as embryological and
      genetic insights accumulate. This review focuses on novel studies of the origins,
      composition and evolution of distinct craniofacial muscles. Cellular and
      molecular parallels are drawn between cardiac and branchiomeric muscle
      developmental programs, both of which utilize multiple lineages with distinct
      developmental histories, and argue for the tissues' common evolutionary origin.
      In addition, there is increasing evidence that the specification of skeletal
      muscles in the head appears to be distinct from that operating in the trunk:
      considerable variation among the different craniofacial muscle groups is seen, in
      a manner resembling myogenic specification in lower organisms.

PMID- 19162002
TI  - Cell communication with the neural plate is required for induction of neural
      markers by BMP inhibition: evidence for homeogenetic induction and implications
      for Xenopus animal cap and chick explant assays.
AB  - In Xenopus, the animal cap is very sensitive to BMP antagonists, which result in
      neuralization. In chick, however, only cells at the border of the neural plate
      can be neuralized by BMP inhibition. Here we compare the two systems. BMP
      antagonists can induce neural plate border markers in both ventral Xenopus
      epidermis and non-neural chick epiblast. However, BMP antagonism can only
      neuralize ectodermal cells when the BMP-inhibited cells form a continuous trail
      connecting them to the neural plate or its border, suggesting that homeogenetic
      neuralizing factors can only travel between BMP-inhibited cells. Xenopus animal
      cap explants contain cells fated to contribute to the neural plate border and
      even to the anterior neural plate, explaining why they are so easily neuralized
      by BMP-inhibition. Furthermore, chick explants isolated from embryonic epiblast
      behave like Xenopus animal caps and express border markers. We propose that the
      animal cap assay in Xenopus and explant assays in the chick are unsuitable for
      studying instructive signals in neural induction.

PMID- 19162004
TI  - Drosophila mir-9a regulates wing development via fine-tuning expression of the
      LIM only factor, dLMO.
AB  - MicroRNAs are short non-coding endogenous RNAs that are implicated in regulating
      various aspects of plants and animal development, however their functions in
      organogenesis are largely unknown. Here we report that mir-9a belonging to the
      mir-9 family, regulates Drosophila wing development through a functional target
      site in the 3' untranslated region of the Drosophila LIM only protein, dLMO. dLMO
      is a transcription cofactor, that directly inhibits the activity of Apterous, the
      LIM-HD factor required for the proper dorsal identity of the wings. Deletions of
      the 3' untranslated region, including the mir-9a site, generate gain-of-function
      dLMO mutants (Beadex) associated with high levels of dLMO mRNA and protein.
      Beadex mutants lack wing margins, a phenotype also observed in null mir-9a
      mutants. We found that mir-9a and dLMO are co-expressed in wing discs and
      interact genetically for controlling wing development. Lack of mir-9a results in
      overexpression of dLMO, while gain-of-function mir-9a mutant suppresses dLMO
      expression. These data indicate that a function of mir-9a is to ensure the
      appropriate stoichiometry of dLMO during Drosophila wing development. The mir-9a
      binding site is conserved in the human counterpart LMO2, the T-cell acute
      leukemia oncogene, suggesting that mir-9 might apply a similar strategy to
      maintain LMO2 expression under a detrimental threshold.

PMID- 19162006
TI  - Cx43 contributes to TGF-beta signaling to regulate differentiation of cardiac
      fibroblasts into myofibroblasts.
AB  - Differentiation and activation of fibroblasts into myofibroblasts which express
      alpha-smooth muscle actin (alpha-SMA) are essential for wound healing and tissue
      repair. Change in fibroblast properties is initiated by transforming growth
      factor beta (TGF-beta). Here, we sought to investigate whether connexin43 (Cx43),
      a gap-junctional protein, contributes to differentiation of cardiac fibroblasts
      to myofibroblasts. In cultured neonatal rat cardiac fibroblasts, we found that
      expression of alpha-SMA increases in parallel with Cx43 by using
      immunocytochemistry, and that knockdown of the endogenous Cx43 activity with
      antisense oligodeoxynucleotides (AS) inhibits alpha-SMA expression significantly,
      while overexpression of Cx43 increases alpha-SMA expression remarkably. These
      findings demonstrate that Cx43 contributes to TGF-beta signaling to regulate
      alpha-SMA expression. Thus, we propose a novel physiologic function of Cx43,
      which plays a critical role in the pathological activation of cardiac fibroblasts
      in the myocardial fibrosis associated with heart failure.

PMID- 19162005
TI  - Response gene to complement 32 is required for C5b-9 induced cell cycle
      activation in endothelial cells.
AB  - Proliferation of vascular endothelial cells (EC) and smooth muscle cells (SMC) is
      a critical event in angiogenesis and atherosclerosis. We previously showed that
      the C5b-9 assembly during complement activation induces cell cycle in human
      aortic EC (AEC) and SMC. C5b-9 can induce the expression of Response Gene to
      Complement (RGC)-32 and over expression of this gene leads to cell cycle
      activation. Therefore, the present study was carried out to test the requirement
      of endogenous RGC-32 for the cell cycle activation induced by C5b-9 by knocking
      down its expression using siRNA. We identified two RGC-32 siRNAs that can
      markedly reduce the expression of RGC-32 mRNA in AEC. RGC-32 silencing in these
      cells abolished DNA synthesis induced by C5b-9 and serum growth factors,
      indicating the requirement of RGC-32 activity for S-phase entry. RGC-32 siRNA
      knockdown also significantly reduced the C5b-9 induced CDC2 activation and Akt
      phosphorylation. CDC2 does not play a role in G1/S transition in HeLa cells
      stably overexpressing RGC-32. RGC-32 was found to physically associate with Akt
      and was phosphorylated by Akt in vitro. Mutation of RGC-32 protein at Ser 45 and
      Ser 47 prevented Akt mediated phosphorylation. In addition, RGC-32 was found to
      regulate the release of growth factors from AEC. All these data together suggest
      that cell cycle induction by C5b-9 in AEC is RGC-32 dependent and this is in part
      through regulation of Akt and growth factor release.

PMID- 19162008
TI  - Focus on molecules: guanylate cyclase-activating proteins (GCAPs).

PMID- 19162007
TI  - VEGFR1 receptor tyrosine kinase localization to the Golgi apparatus is calcium
      dependent.
AB  - Vascular endothelial growth factor receptor 1 (VEGFR1) is an essential receptor
      tyrosine kinase that regulates mammalian vascular development and embryogenesis
      but its function is not well understood. Herein, we present evidence whereby
      endothelial VEGFR1 is largely resident within the Golgi apparatus but
      translocates to the plasma membrane via a calcium-regulated process. Primary
      human endothelial cells reveal differing VEGFR1 and VEGFR2 intracellular
      distribution and dynamics. The major proportion of the full-length VEGFR1
      membrane protein was resident within the Golgi apparatus in primary endothelial
      cells. Whereas VEGFR2 displayed down-regulation in response to VEGF-A, VEGFR1 was
      not significantly affected arguing for a significant intracellular pool that was
      inaccessible to extracellular VEGF-A. This intracellular VEGFR1 pool showed
      significant co-distribution with key Golgi residents. Brefeldin A caused VEGFR1
      Golgi fragmentation consistent with redistribution to the endoplasmic reticulum.
      Metabolic labeling experiments and microscopy using domain-specific VEGFR1
      antibodies indicated that the mature processed VEGFR1 species and an integral
      membrane protein was resident within Golgi apparatus. Cytosolic calcium ions play
      a key role in VEGFR1 trafficking as treatment with either VEGF-A, histamine,
      thrombin, thapsigargin or A23187 ionophore caused VEGFR1 redistribution from the
      Golgi apparatus to small punctate vesicles and plasma membrane. We thus propose a
      model whereby the balance of VEGFR1 and VEGFR2 plasma membrane levels dictate
      either negative or positive endothelial signaling to influence vascular
      physiology.

PMID- 19162009
TI  - Changes in the localization of collagens IV and VIII in corneas obtained from
      patients with posterior polymorphous corneal dystrophy.
AB  - Posterior polymorphous corneal dystrophy (PPCD) is a hereditary bilateral
      disorder affecting primarily the endothelium and Descemet's membrane (DM). The
      aim of this study was to determine the changes in the presence and localization
      of the alpha1-alpha6 collagen IV chains and alpha1, alpha2 collagen VIII chains
      in Czech patients with PPCD. Twelve corneal buttons from ten PPCD patients who
      underwent corneal grafting, as well as eight unaffected corneas, were used.
      Enzymatic indirect immunohistochemistry was performed on cryosections using
      antibodies against the alpha1-alpha6 collagen IV chains and alpha1, alpha2
      collagen VIII chains. The intensity of the signal was examined separately in the
      basal membrane of the epithelium (BME), stroma and DM. More than 50% of PPCD
      specimens exhibited positivity for alpha1 and alpha2 collagen IV chains in the
      BME and in the posterior stroma, while no staining was detected in these areas in
      control specimens. The signal for the alpha1 and alpha2 collagen IV chains was
      more intense in DM of PPCD corneas compared to controls and it was shifted from
      the stromal side (in control tissue) to the endothelial side of DM (in the
      patients). A less intensive signal in PPCD corneas for the alpha3 and alpha5
      chains in DM and an accumulation of alpha3-alpha5 in the posterior stroma in
      diseased corneas were the only differences in staining for the alpha3-alpha6
      collagen IV chains. The alpha1 collagen VIII chain was detected on both the
      endothelial and the stromal sides of DM in 90% of patients with PPCD, compared
      with the prevailing localization on the stromal side of DM in control corneas. A
      change in the localization of the alpha2 collagen VIII chain in DM from
      vertically striated features in control specimens to double line positivity in
      the DM of PPCD corneas and positive staining in the posterior collagenous layer
      of four patients were also detected. In three PPCD patients a fibrous pannus
      located under the BME, positive for alpha1-alpha3, alpha5 collagen IV chains and
      alpha1 collagen VIII chain, was observed. The increased expression of the alpha1,
      alpha2 collagen IV and alpha1 collagen VIII chains and the change in their
      localization in DM may contribute to the increased endothelial proliferative
      capacity observed in PPCD patients.

PMID- 19162010
TI  - Sexual dimorphic stages affect both proliferation and serotonergic innervation in
      the adult rostral migratory stream.
AB  - One of the sexual dimorphic differences in adult rodents is neural proliferation.
      Here we demonstrate that physiological hormone stages can modulate this
      proliferation in the adult forebrain. Female mice, both pregnant and synchronized
      in oestrus, exhibited higher proliferating cell percentages than males in both
      the rostral migratory stream (RMS) and the olfactory bulb (OB). Moreover,
      although the hormonal component also influenced the subventricular zone (SVZ), no
      differences in proliferation were observed in this region. In addition, both
      groups of females had higher numbers of serotonergic fibres in these regions.
      Serotonin may therefore be related to the mechanism of action by which hormones
      can affect cell proliferation of this brain region. We also evaluated cell death
      in the SVZ in males and females, finding that this was higher in the former.
      Taken together, our results support the idea that in female rodents more
      neuroblasts are able to reach the RMS and then proliferate, apoptosis being an
      additional mechanism affecting the low proliferation of cells in the RMS and OB
      in males. Thus, proliferation in the RMS is influenced by sexual dimorphism.

PMID- 19162011
TI  - Corticosterone facilitates extinction of fear memory in BALB/c mice but
      strengthens cue related fear in C57BL/6 mice.
AB  - Corticosterone, the naturally occurring glucocorticoid of rodents is secreted in
      response to stressors and is known for its facilitating and detrimental effects
      on emotional learning and memory. The large variability in the action of
      corticosterone on processing of emotional memories is postulated to depend on
      genetic background and the spatio-temporal domain in which the hormone operates.
      To address this hypothesis, mice of two strains with distinct corticosterone
      secretory patterns and behavioural phenotype (BALB/c and C57BL/6J) were treated
      with corticosterone (250 microg/kg, i.p.), either 5 min before or directly after
      acquisition in a fear conditioning task. As the paradigm allowed assessing in one
      experimental procedure both context- and cue-related fear behaviour, we were able
      to detect generalization and specificity of fear. BALB/c showed generalized
      strong fear memory, while C57BL/6J mice discriminated between freezing during
      context- and cue episodes. Corticosterone had opposite effects on fear memory
      depending on the strain and time of injection. Corticosterone after acquisition
      did not affect C57BL/6J mice, but destabilized consolidation and facilitated
      extinction in BALB/c. Corticosterone 5 min before acquisition strengthened stress
      associated signals: BALB/c no longer showed lower fear memory, while C57BL/6J
      mice displayed increased fear memory and impaired extinction in cue episodes. We
      propose that corticosterone-induced facilitation of fear memory in C57BL/6J mice
      can be used to study the development of fear memories, corticosterone
      administration in BALB/c mice presents a model to examine treatment. We conclude
      that genetic background and time of corticosterone action are modifiers of fear
      memory with interesting translational implications for anxiety-related diseases.

PMID- 19162012
TI  - Mexiletine-responsive erythromelalgia due to a new Na(v)1.7 mutation showing use
      dependent current fall-off.
AB  - Inherited erythromelalgia (IEM), characterized by episodic burning pain and
      erythema of the extremities, is produced by gain-of-function mutations in sodium
      channel Na(v)1.7, which is preferentially expressed in nociceptive and
      sympathetic neurons. Most patients do not respond to pharmacotherapy, although
      occasional reports document patients as showing partial relief with lidocaine or
      mexiletine. A 7-year-old girl, with a two-year history of symmetric burning pain
      and erythema in her hands and feet, was diagnosed with erythromelalgia. Treatment
      with mexiletine reduced the number and severity of pain episodes. We report here
      a new IEM Na(v)1.7 mutation in this patient, and its response to mexiletine.
      SCN9A exons from the proband were amplified and sequenced. We identified a single
      nucleotide substitution (T2616G) in exon 15, not present in 200 ethnically
      matched control alleles, which substitutes valine 872 by glycine (V872G) within
      DII/S5. Whole-cell patch-clamp analysis of wild-type and mutant Na(v)1.7 channels
      in mammalian cells show that V872G shifts activation by -10 mV, slows
      deactivation, and generates larger ramp currents. We observed a stronger use
      dependent fall-off in current following exposure to mexiletine for V872G compared
      to wild-type channels. These observations suggest that some patients with IEM may
      show a favorable response to mexiletine due to a use-dependent effect on mutant
      Na(v)1.7 channels. Continued relief from pain, even after mexiletine was
      discontinued in this patient, might suggest that early treatment may slow the
      progression of the disease.

PMID- 19162013
TI  - The role of interleukin-1 in seizures and epilepsy: a critical review.
AB  - Interleukin-1 (IL-1) has a multitude of functions in the central nervous system.
      Some of them involve mechanisms that are related to epileptogenesis. The role of
      IL-1 in seizures and epilepsy has been investigated in both patients and animal
      models. This review aims to synthesize, based on the currently available
      literature, the consensus role of IL-1 in epilepsy. Three lines of evidence
      suggest a role for IL-1: brain tissue from epilepsy patients and brain tissue
      from animal models shows increased IL-1 expression after seizures, and IL-1 has
      proconvulsive properties when applied exogeneously. However, opposing results
      have been published as well. More research is needed to fully establish the role
      of IL-1 in seizure generation and epilepsy, and to explore possible new treatment
      strategies that are based on interference with intracellular signaling cascades
      that are initiated when IL-1 binds to its receptor.

PMID- 19162015
TI  - High cytotoxic sensitivity of the oligodendrocyte precursor cells to HSP90
      inhibitors in cell cultures.
AB  - Oligodendrocyte precursor cells (OPCs) are able to proliferate, and most
      differentiate into post-mitotic oligodendrocytes that contribute to
      remyelination. We have previously studied the expression of heat shock protein90
      (HSP90) in OPCs. The ansamycins, such as geldanamycin and 17-allylamino-17
      demethoxygeldanamycin (17-AAG) act as specific HSP90 inhibitors, are potent anti
      tumor agents and are currently undergoing clinical trials. This work investigated
      the effect of HSP90 inhibitors on cultured OPCs. Geldanamycin, 17-AAG and another
      chemically unrelated HSP90 inhibitor, radicicol, were extremely cytotoxic for
      OPCs. The IC50 values of geldanamycin, 17-AAG and radicicol for OPCs were 7.1,
      10.7 and 137 nM, respectively, compared to 1000-2000 nM for preoligodendrocytes,
      astrocytes and neurons. Adult OPCs were found to be susceptible to HSP90
      inhibitors in a similar fashion to perinatal cells. OPC death induced by these
      HSP90 inhibitors led to a significant decrease in the oligodendrocyte population.
      The present results highlight that OPCs are uniquely sensitive to HSP90
      inhibitors. Geldanamycin and 17-AAG, which penetrate the blood-brain barrier, are
      novel cancer chemotherapeutic agents and we noted that, in anti-cancer therapy
      with these drugs, the OPCs may be compromised.

PMID- 19162014
TI  - Mechanical reperfusion is associated with post-ischemic hemorrhage in rat brain.
AB  - A major complication of recanalization therapy after an acute arterial occlusion
      in brain is hemorrhagic transformation (HT). Although it is known that prolonged
      ischemia is important in the development of HT, the role of reperfusion in
      ischemia-reperfusion induced HT is less well studied. To address the effect of
      reperfusion on HT, we assessed the incidence and severity of hemorrhage in rats
      after 5 h of middle cerebral artery occlusion (MCAO) followed by 19-hour
      reperfusion compared to rats with permanent occlusion (PMCAO) at the same 24-hour
      time point. The incidence and amount of hemorrhage, neurological function, and
      mortality rates were measured. MCAO (5 h) with 19-hour reperfusion was associated
      with a significantly higher incidence of cortical hemorrhage compared to PMCAO
      (81.8% vs 18.2%, p<0.05). Hemorrhage scores were higher in the 5-hour
      MCAO/reperfusion group compared to PMCAO rats (17.6+/-11.5 vs 2.4+/-5.3 in
      cortex, 20.4+/-4.6 vs 9.7+/-4.5 in striatum, p<0.01). Neurological function was
      worse in the ischemia-reperfusion group compared to PMCAO (p<0.05) and mortality
      rates were insignificantly higher in the 5-hour MCAO/reperfusion group vs PMCAO
      group (54.5% vs 18.1%; p<0.08). The results suggest that reperfusion after
      prolonged ischemia is associated with increased hemorrhagic transformation and
      neurological deterioration as compared to permanent ischemia. Whether
      pharmacological treatments prior to reperfusion attenuate post-ischemic HT
      requires further study.

PMID- 19162016
TI  - GDNF released from encapsulated cells suppresses seizure activity in the
      epileptic hippocampus.
AB  - To date, a variety of pharmacological treatments exists for patients suffering
      epilepsy, but systemically administered drugs offer only symptomatic relief and
      often cause unwanted side effects. Moreover, available drugs are not effective in
      one third of the patients. Thus, more local and more effective treatment
      strategies need to be developed. Gene therapy-based expression of endogenous anti
      epileptic agents represents a novel approach that could interfere with the
      disease process and result in stable and long-term suppression of seizures in
      epilepsy patients. We have reported earlier that direct in vivo viral vector
      mediated overexpression of the glial cell line-derived neurotrophic factor (GDNF)
      in the rat hippocampus suppressed seizures in different animal models of
      epilepsy. Here we explored whether transplantation of encapsulated cells that
      release GDNF in the hippocampus could also exert a seizure-suppressant effect.
      Such ex vivo gene therapy approach represents a novel, more clinically safe
      approach, since the treatment could be terminated by retrieving the transplants
      from the brain. We demonstrate here that encapsulated cells, which are
      genetically modified to produce and release GDNF, can suppress recurrent
      generalized seizures when implanted into the hippocampus of kindled rats.

PMID- 19162017
TI  - Enhanced recovery of human spinothalamic function is associated with central
      neuropathic pain after SCI.
AB  - Spinothalamic tract (STT) dysfunction seems to be crucially involved in the
      development of central neuropathic pain (NP) after spinal cord injury (SCI).
      However, previous attempts to identify differences in the extent or location of
      STT damage between subjects with and without NP failed. Here we show that the
      spontaneous recovery of human STT function (within the first year after SCI) in
      subjects suffering NP is enhanced compared to those not affected. Furthermore,
      the correlation between current pain intensity (assessed on average 5 years after
      SCI) and extent of functional recovery substantiates the close relationship
      between recovery of STT function and the occurrence of NP. These findings
      contribute to a better understanding of mechanisms involved in the generation of
      NP after SCI.

PMID- 19162018
TI  - The crystal structure of C176A mutated [Fe]-hydrogenase suggests an acyl-iron
      ligation in the active site iron complex.
AB  - [Fe]-hydrogenase is one of three types of enzymes known to activate H(2). Crystal
      structure analysis recently revealed that its active site iron is ligated square
      pyramidally by Cys176-sulfur, two CO, an "unknown" ligand and the sp(2)
      hybridized nitrogen of a unique iron-guanylylpyridinol-cofactor. We report here
      on the structure of the C176A mutated enzyme crystallized in the presence of
      dithiothreitol (DTT). It suggests an iron center octahedrally coordinated by one
      DTT-sulfur and one DTT-oxygen, two CO, the 2-pyridinol's nitrogen and the 2
      pyridinol's 6-formylmethyl group in an acyl-iron ligation. This result led to a
      re-interpretation of the iron ligation in the wild-type.

PMID- 19162019
TI  - Suppression of the ecdysteroid-triggered growth arrest by a novel Drosophila
      membrane steroid binding protein.
AB  - Ecdysteroid is a crucial steroid hormone in insects, especially during
      metamorphosis. Here, we show that the Drosophila membrane steroid binding protein
      (Dm_MSBP) is a novel structural homolog of the vertebrate membrane-bound receptor
      component for progesterone. Dm_MSBP exhibited binding affinity to ecdysone when
      expressed on the cell surface of Drosophila S2 cells. In S2 cells, the stable
      overexpression of Dm_MSBP suppressed the growth arrest triggered by 20
      hydroxyecdysone and prevented the temporal activation of extracellular signal
      regulated kinase proteins. These results suggest that Dm_MSBP is a membranous
      suppressor to ecdysteroid and blocks the signaling by binding it in extracellular
      fluid.

PMID- 19162020
TI  - Leucine-rich hydrophobic clusters promote folding of the N-terminus of the
      intrinsically disordered transactivation domain of p53.
AB  - Molecular dynamics simulations have been performed on the intrinsically
      disordered 39-residue N-terminal transactivation domain of p53 (p53(1-39)).
      Simulations not only revealed that p53(1-39) is natively compact, but also
      possesses a folded structure. Furthermore, leucine-rich hydrophobic clusters were
      found to play a crucial role in the formation and stabilization of the folded
      structure of p53(1-39). Collapsing in the sub-microsecond timescale might allow
      for rapid conformational turnovers of p53(1-39), necessary for its efficient
      transactivation activity and modulation. Fast collapsing might be the result of
      unique conformational landscapes, featuring several energy minima separated by
      small energy barriers. It is suggested that IDPs with highly specialized
      functions in the cell, such as transactivation, possibly display more ordered
      patterns than their less specialized counterparts.

PMID- 19162021
TI  - Differential effects of triterpene glycosides, frondoside A and cucumarioside A2
      2 isolated from sea cucumbers on caspase activation and apoptosis of human
      leukemia cells.
AB  - Frondoside A is a pentaoside having an acetyl moiety at the aglycon ring and
      xylose as a third monosaccharide residue. Cucumarioside A(2)-2 is a pentaoside
      having glucose as a third monosaccahride unit. We compared the effects of
      frondoside A and A(2)-2 for cell death-inducing capability with close attention
      paid to structure-activity relationships. Both frondoside A and A(2)-2 strongly
      induced apoptosis of leukemic cells. Frondoside A-induced apoptosis was more
      potent and rapid than A(2)-2-induced apoptosis. A(2)-2-induced but not frondoside
      A-induced apoptosis was caspase-dependent. This suggests that holothurians may
      induce apoptosis of leukemic cells caspase-dependently or -independently,
      depending on the holothurian structure.

PMID- 19162022
TI  - Conformation-dependent single-chain variable fragment antibodies specifically
      recognize beta-amyloid oligomers.
AB  - Increasing evidence indicates that beta-amyloid (Abeta) oligomers rather than
      monomers or fibrils are the major toxic agents that specifically inhibit synaptic
      plasticity and long-term potentiation (LTP) in Alzheimer's disease (AD).
      Neutralization of Abeta oligomeric toxicity was found to reverse memory deficits.
      Here, we report four single-chain variable fragment (scFv) antibodies isolated
      from the naive human scFv library by phage display that specifically recognized
      Abeta oligomers but not monomers and fibrils. These conformation-dependent scFv
      antibodies inhibit both Abeta fibrillation and cytotoxicity and bind to the same
      type of eptitope displayed on the Abeta oligomers. Such scFv antibodies
      specifically targeting toxic Abeta oligomers may have potential therapeutic and
      diagnostic applications for AD.

PMID- 19162023
TI  - Vitronectin promotes oligodendrocyte differentiation during neurogenesis of human
      embryonic stem cells.
AB  - We demonstrate enhanced differentiation of oligodendrocytes during neurogenesis
      of human embryonic stem cells (hESCs) using an extracellular matrix protein,
      vitronectin (VN). We show that VN is expressed in the ventral part of the
      developing human spinal cord. Combined treatment of retinoic acid, sonic
      hedgehog, and noggin in the presence of VN allows hESCs to differentiate into O4
      positive oligodendrocytes. Particularly, VN profoundly promotes the derivation of
      oligodendrocyte progenitors that proliferate and differentiate into
      oligodendrocytes in response to mitogenic and survival factors. These results
      support the beneficial effect of VN on oligodendrocytic differentiation of hESCs.

PMID- 19162024
TI  - The mammalian nonsense-mediated mRNA decay pathway: to decay or not to decay!
      Which players make the decision?
AB  - Nonsense-mediated mRNA decay (NMD) degrades mRNAs carrying premature translation
      termination codons (PTCs). Although the core process and several NMD effectors
      are conserved among species, the involvement of a splicing-dependent signal seems
      to be specific for mammalian PTC definition. Still, recent data shed new light on
      physical parameters and mechanistic pathways involved in NMD. Here, we examine
      these findings, updating the roles for potential NMD players, such as the exon
      junction complex and the cytoplasmic poly(A)-binding protein 1 - the former
      acting as enhancer rather than an essential factor and the latter functioning as
      NMD repressor.

PMID- 19162025
TI  - Functional characterization of the DnaK chaperone system from the archaeon
      Methanothermobacter thermautotrophicus DeltaH.
AB  - We characterized the biochemical and functional properties of the DnaK system
      from the archaeon Methanothermobacter thermautotrophicus DeltaH. In contrast to
      the eubacterial chaperone components the archaeal Hsp70 system shows thermal
      transitions only slightly above the optimal environmental temperature (65 degrees
      C). Nevertheless, it prevents aggregation of luciferase in the physiological
      temperature range of the organism, but is also fully functional at 30 degrees C
      in luciferase refolding. Additionally, GrpE(M.th.) and DnaJ(M.th.) substitute
      their eubacterial counterparts whereas DnaK(M.th.) is only functional with its
      native cochaperones which could be attributed to a functional specialization of
      the eubacterial chaperones during evolution.

PMID- 19162026
TI  - ZFAT is an antiapoptotic molecule and critical for cell survival in MOLT-4 cells.
AB  - ZFAT (also known as ZNF406), originally identified as a candidate gene for
      autoimmune thyroid disease, encodes a zinc-finger protein, however, its function
      has not been elucidated. Here, we report that human ZFAT protein is expressed in
      peripheral B and T lymphocytes and a human acute T lymphoblastic leukaemia cell
      line, MOLT-4 cells. Intriguing is that mouse ZFAT expression in CD4(+)
      lymphocytes is increased during blast formation. Furthermore, ZFAT-knockdown in
      MOLT-4 induces apoptosis via activation of caspases. These results suggested that
      ZFAT protein is a critical regulator involved in apoptosis and cell survival for
      immune-related cells.

PMID- 19162027
TI  - Prospective derivation and validation of a clinical prediction rule for recurrent
      Clostridium difficile infection.
AB  - BACKGROUND & AIMS: Prevention of recurrent Clostridium difficile infection (CDI)
      is a substantial therapeutic challenge. A previous prospective study of 63
      patients with CDI identified risk factors associated with recurrence. This study
      aimed to develop a prediction rule for recurrent CDI using the above derivation
      cohort and prospectively evaluate the performance of this rule in an independent
      validation cohort. METHODS: The clinical prediction rule was developed by
      multivariate logistic regression analysis and included the following variables:
      age>65 years, severe or fulminant illness (by the Horn index), and additional
      antibiotic use after CDI therapy. A second rule combined data on serum
      concentrations of immunoglobulin G (IgG) against toxin A with the clinical
      predictors. Both rules were then evaluated prospectively in an independent cohort
      of 89 patients with CDI. RESULTS: The clinical prediction rule discriminated
      between patients with and without recurrent CDI, with an area under the curve of
      the receiver-operating-characteristic curve of 0.83 (95% confidence interval
      [CI]: 0.70-0.95) in the derivation cohort and 0.80 (95% CI: 0.67-0.92) in the
      validation cohort. The rule correctly classified 77.3% (95% CI: 62.2%-88.5%) and
      71.9% (95% CI: 59.2%-82.4%) of patients in the derivation and validation cohorts,
      respectively. The combined rule performed well in the derivation cohort but not
      in the validation cohort (area under the curve of the receiver-operating
      characteristic curve, 0.89 vs 0.62; diagnostic accuracy, 93.8% vs 69.2%,
      respectively). CONCLUSIONS: We prospectively derived and validated a clinical
      prediction rule for recurrent CDI that is simple, reliable, and accurate and can
      be used to identify high-risk patients most likely to benefit from measures to
      prevent recurrence.

PMID- 19162028
TI  - The association between alcohol and reflux esophagitis, Barrett's esophagus, and
      esophageal adenocarcinoma.
AB  - BACKGROUND & AIMS: Alcohol consumption may increase gastroesophageal reflux
      symptoms, cause damage to the esophageal mucosa, and/or promote carcinogenesis.
      However, reports about the association between alcohol and reflux esophagitis,
      Barrett's esophagus, and esophageal adenocarcinoma are conflicting. METHODS:
      Information relating to alcohol consumption, at age 21 and 5 years before the
      interview date, was collected from 230 reflux esophagitis, 224 Barrett's
      esophagus, and 227 esophageal adenocarcinoma patients and 260 frequency-matched
      population controls. Logistic regression analyses were used to compare alcohol
      consumption in the 3 case groups to controls with adjustment for potential
      confounders. RESULTS: Population controls reporting gastroesophageal reflux
      symptoms were less likely than controls without symptoms to drink alcohol 5 years
      before the interview date (odds ratio [OR], 0.44, 0.20-0.99). No associations
      were observed between total alcohol consumption 5 years before the interview date
      and reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma (OR,
      1.26, 0.78-2.05; OR, 0.72, 0.43-1.21; and OR, 0.75, 0.46-1.22, respectively).
      Wine was inversely associated with reflux esophagitis (OR, 0.45, 0.27-0.75).
      Total alcohol consumption at age 21 years was significantly associated with
      reflux esophagitis (OR, 2.24, 1.35-3.74) but not with Barrett's esophagus or
      esophageal adenocarcinoma (OR, 1.06, 0.63-1.79 and OR, 1.27, 0.77-2.10,
      respectively). CONCLUSIONS: Alcohol consumption in early adulthood may lead to
      the development of reflux esophagitis. More recent alcohol consumption does not
      appear to confer any increased risk of reflux esophagitis, Barrett's esophagus,
      or esophageal adenocarcinoma. In fact, wine consumption may reduce the risk of
      these 3 esophageal disorders.

PMID- 19162029
TI  - The recurrence of acute alcohol-associated pancreatitis can be reduced: a
      randomized controlled trial.
AB  - BACKGROUND & AIMS: In the long term, half of patients with their first alcohol
      associated acute pancreatitis (AP) develop acute recurrence, alcohol consumption
      being the main risk factor. None of the recent national or international
      guidelines for treatment include recommendations aimed to decrease recurrences,
      possibly because of a lack of studies. This study investigated whether AP
      recurrences can be reduced. METHODS: One hundred and twenty patients admitted to
      a university hospital for their first alcohol-associated AP were randomized
      either to repeated intervention (n = 59) or initial intervention only (n = 61).
      The patients in the 2 groups did not differ. A registered nurse performed an
      intervention in both groups before discharge, after which it was repeated in the
      study group at 6-month intervals at the gastrointestinal outpatient clinic. Acute
      recurrences during the next 2 years were monitored. RESULTS: There were 9
      recurrent AP episodes in 5 patients in the repeated-intervention group compared
      with 20 episodes (P = .02) in 13 patients (P = .04) in the control group. The
      recurrence rates were similar during the first 6 months (4 vs 5 episodes), after
      which the repeated-intervention group had fewer recurrences than the control
      group (5 vs 15 episodes; P = .02). CONCLUSIONS: The repeated visits at 6-month
      intervals at the gastrointestinal outpatient clinic, consisting of an
      intervention against alcohol consumption, appear to be better than the single
      standardized intervention alone during hospitalization in reducing the
      development of recurrent AP during a 2-year period.

PMID- 19162030
TI  - High self-perceived stress and many stressors, but normal diurnal cortisol
      rhythm, in adults with ADHD (attention-deficit/hyperactivity disorder).
AB  - Attention-deficit/hyperactivity disorder (ADHD) in adults is associated with
      significant impairment in many life activities and may thus increase the risk of
      chronic stress in everyday life. We compared adults with a DSM-IV ADHD diagnosis
      (n=28) with healthy controls (n=28) regarding subjective stress and amounts of
      stressors in everyday life, diurnal salivary cortisol in the everyday environment
      and salivary cortisol before and after cognitive stress in a laboratory setting.
      The association between cortisol concentrations and impulsivity was also
      investigated. Consistent with assumptions, individuals with ADHD reported
      significantly more self-perceived stress than controls, and subjective stress
      correlated with the amount of stressors in everyday life. The two groups were
      comparable with respect to overall diurnal cortisol levels and rhythm, as well as
      in pre- and post-stress cortisol concentrations. Post-stress cortisol (but not
      baseline cortisol) concentration was positively correlated with impulsivity. The
      group with high post-stress cortisol also reported more symptoms of depression
      and anxiety, as well as self-perceived stress and stressors in every-day life.
      The diagnosis of ADHD significantly increased the risk of belonging to the group
      with high post-stress cortisol levels. The results in this study warrant a focus
      not only on the primary diagnosis of ADHD, but also calls for a broader
      assessment of stressors and subjective stress in everyday life, as well as
      support comprising stress management and coping skills.

PMID- 19162031
TI  - Preferential transcription of conserved rif genes in two phenotypically distinct
      Plasmodium falciparum parasite lines.
AB  - Plasmodium falciparum variant surface antigens (VSA) are targets of protective
      immunity to malaria. Plasmodium falciparum erythrocyte membrane protein 1
      (PfEMP1) and repetitive interspersed family (RIFIN) proteins are encoded by the
      two variable multigene families, var and rif genes, respectively. Whereas PfEMP1s
      are known to mediate cytoadhesion, the function of RIFINs is unknown. The
      sequence diversity and organisation of rif genes of the P. falciparum clones 3D7,
      HB3, DD2, and IT/FCR3 were investigated using a tree-building method which
      allowed sub-grouping of RIFINs into distinct groups. Two novel rif gene groups,
      rifA1 and rifA2, containing inter-genomic conserved rif genes, were identified.
      All rifA1 genes were orientated head-to-head with a neighbouring Group A var gene
      whereas rifA2 was present in all parasite genomes as a single copy gene with a
      unique 5' untranslated region. Rif transcript levels were determined in two
      different parasite lines, 3D7-Lib and NF54-VAR2CSA, expressing VSA associated
      with severe malaria in children and pregnant women, respectively. The 3D7-Lib
      showed high transcript levels of Group A var and neighbouring rif genes, whereas
      rifA2 was found highly transcribed in the VAR2CSA-expressing parasite line. In
      addition, two rif genes were found transcribed at early and late intra
      erythrocyte stages independently of var gene transcription. Rif genes are
      organised in groups and inter-genomic conserved gene families, suggesting that
      RIFIN sub-groups may have different functional capacities. This conclusion is
      experimentally supported by group-specific rif transcription in parasites with
      different VSA and PfEMP1 expression phenotypes.

PMID- 19162032
TI  - Identification and testing of control peptides for antigen microarrays.
AB  - INTRODUCTION: Peptide microarray slides usually contain positive control spots to
      gauge for antibody binding. Unlike the good response on earlier prototype
      microarrays, human immunoglobulin controls do not function consistently on newer
      generation slides. This may be due to technical problems in high-density printing
      or degradation. Our objective was to identify and print reliable control peptides
      that did not suffer from the same problems as proteins. METHODS: Peptide
      microarray slides containing 10,000-23,000 synthetic peptides spanning proteins
      involved in M. tuberculosis or Bordatella pertussis were incubated with secondary
      antibody in sample dilution buffer. After removal of artefacts due to slide
      architecture, we identified peptides that gave a high mean response and low co
      efficient of variation across all replicates. These control peptides were tested
      for their performance on newly manufactured slides. RESULTS: We selected three
      peptides on the TB slides and three peptides on the B. pertussis slides that had
      a mean response index of at least 5 and a coefficient of variation less than 15%.
      When used as controls in newly-designed slides, these peptides gave consistently
      high responses: the median index ranged from 4.5 to 9.5 in the absence of patient
      serum and was of a somewhat lesser magnitude when incubated with patient serum.
      We illustrate the use of these control responses to normalize the peptide
      responses on a set of slides prepared with human serum. CONCLUSIONS: Our work
      shows that it is possible to identify control peptides that can be used when
      protein controls do not function consistently. This has important consequences
      for the storage of peptide-microarrays and their use in the field: protein chips
      need to be kept at +4 degrees C while peptide chips can be kept at room
      temperature. Although we focused on TB and B. pertussis, our methodology has
      relevance for any disease or disorder where peptide arrays are used to assess
      immune response.

PMID- 19162033
TI  - Transient host paralysis as a means of reducing self-superparasitism in
      koinobiont endoparasitoids.
AB  - The term 'idiobiont' refers to those parasitoid species that permanently paralyse
      their hosts during parasitism, causing the cessation of host growth and
      development. This is in contrast to koinobiont parasitoids, which allow their
      hosts to continue developing after being parasitized. While no koinobiont species
      induce permanent paralysis in their hosts, a minority of koinobionts induce a
      temporary paralysis that does not interfere with overall host growth and
      development. We characterized transient paralysis induction in two koinobiont
      aphid parasitoids in the genus Binodoxys (Hymenoptera: Aphidiinae). Both
      Binodoxys species induced transient paralysis in Aphis glycines, with paralysis
      time ranging between 4.5 and 8 min (depending upon parasitoid species and host
      instar). In a separate experiment, B. communis was capable of inducing transient
      paralysis in nine aphid species. We addressed two hypotheses potentially
      explaining the adaptive value of temporary host paralysis in experiments using A.
      nerii, which is readily accepted but engages in strong defensive behaviour. The
      first hypothesis is that paralysis increases oviposition success by interfering
      with host defences and the second is that it aids in the avoidance of self
      superparasitism. Paralysed aphids were more likely to be rejected by B. communis
      than were aphids that had never been stung or that had recovered from paralysis.
      This result supports the avoidance-of-self-superparasitism hypothesis and is
      inconsistent with the hypothesis that transient paralysis increases oviposition
      success of B. communis.

PMID- 19162034
TI  - Mitochondrial Ca2+ uptake: tortoise or hare?
AB  - Mitochondria are equipped with an efficient machinery for Ca(2+) uptake and
      extrusion and are capable of storing large amounts of Ca(2+). Furthermore, key
      steps of mitochondrial metabolism (ATP production) are Ca(2+)-dependent. In the
      field of cardiac physiology and pathophysiology, two main questions have
      dominated the thinking about mitochondrial function in the heart: 1) how does
      mitochondrial Ca(2+) buffering shape cytosolic Ca(2+) levels and affect
      excitation-contraction coupling, particularly the Ca(2+) transient, on a beat-to
      beat basis, and 2) how does mitochondrial Ca(2+) homeostasis influence cardiac
      energy metabolism. To answer these questions, a thorough understanding of the
      kinetics of mitochondrial Ca(2+) transport and buffer capacity is required. Here,
      we summarize the role of mitochondrial Ca(2+) signaling in the heart, discuss the
      evidence either supporting or arguing against the idea that Ca(2+) can be taken
      up rapidly by mitochondria during excitation-contraction coupling and highlight
      some interesting new areas for further investigation.

PMID- 19162035
TI  - Cardiac interstitial cells express GATA4 and control dedifferentiation and cell
      cycle re-entry of adult cardiomyocytes.
AB  - Interstitial cells of the adult rat heart were characterized with respect to i)
      expression of cardiac markers of commitment and differentiation, ii) myogenic
      potential in vitro and iii) ability to modulate cardiomyocyte differentiation
      state. We demonstrate for the first time that fibroblasts and a proportion of
      pericytes in the adult rat heart express the transcription factor GATA4. This
      appears to be a peculiar property of the heart. Fibroblasts that are also derived
      from the splanchnopleuric mesoderm, such as those of the gut, or fibroblasts of
      different embryological origin, such as those of skin and skeletal muscle, lack
      this property. Of note, a nestin+/GATA4+ putative stem cell population is also
      detected in the adult heart. GATA4+ cardiac interstitial cells do not display
      myogenic potential in vitro. However, cardiac fibroblasts, but not skin
      fibroblasts, stimulate dedifferentiation of adult cardiomyocytes and their re
      entry into the cell cycle in vitro, as demonstrated by the high number of
      cardiomyocytes expressing Ki67, phosphorylated histone H3 (H3P) and incorporating
      5-bromodeoxiuridine (BrdU) in the co-cultures. In conclusion, cardiac fibroblasts
      have peculiar expression of myogenic transcription factors, a property that may
      have an impact for reprogramming these cells to the myogenic differentiation. In
      addition, they are able to modulate the behavior of adult cardiomyocytes, a
      property that may be used to promote dedifferentiation and proliferation of
      cardiac cells in the damaged myocardium.

PMID- 19162036
TI  - "Change can happen" by PKA: proteasomes in in vivo hearts.

PMID- 19162037
TI  - CB(2) cannabinoid receptor activation is cardioprotective in a mouse model of
      ischemia/reperfusion.
AB  - Preventive treatment with cannabinoid agonists has been reported to reduce the
      infarct size in a mouse model of myocardial ischemia/reperfusion. Here we
      investigated the possible cardioprotective effect of selective CB(2) cannabinoid
      receptor activation during ischemia. We performed left coronary artery ligature
      in C57Bl/6 mice for 30 min, followed by 24 h of reperfusion. Five minutes before
      reperfusion, mice received intraperitoneal injection of the CB(2) selective
      agonist JWH-133 (20 mg/kg) or vehicle. Infarct size was assessed histologically
      and by cardiac troponin I (cTnI) ELISA. Immunohistochemical analysis of leukocyte
      infiltration, oxidative stress in situ quantification, real-time RT-PCR analysis
      of inflammatory mediators as well as western blots for kinase phosphorylation was
      also performed. In addition, we studied chemotaxis and integrin expression of
      human neutrophils in vitro. JWH-133 significantly reduced the infarct size
      (I/area at risk: 19.27%+/-1.91) as compared to vehicle-treated mice (31.77%+/
      2.7). This was associated with a reduction of oxidative stress and neutrophil
      infiltration in the infarcted myocardium, whereas activation of ERK 1/2 and STAT
      3 was increased. Preinjection of PI3K inhibitor LY294002, MEK 1/2 inhibitor U0126
      and JAK-2 inhibitor AG-490 partially abrogated the JWH-133 mediated infarct size
      reduction. No changes in cardiac CXCL1, CXCL2, CCL3, TNF-alpha, and ICAM-1
      expression levels were found. Furthermore, JWH-133 inhibited the TNF-alpha
      induced chemotaxis and integrin CD18/CD11b (Mac-1) upregulation on human
      neutrophils. Our data suggest that JWH-133 administration during ischemia reduces
      the infarct size in a mouse model of myocardial ischemia/reperfusion through a
      direct cardioprotective activity on cardiomyocytes and neutrophils.

PMID- 19162038
TI  - Genetic deletion of MAO-A promotes serotonin-dependent ventricular hypertrophy by
      pressure overload.
AB  - The potential role of serotonin (5-HT) in cardiac function has generated much
      interest in recent years. In particular, the need for a tight regulation of 5-HT
      to maintain normal cardiovascular activity has been demonstrated in different
      experimental models. However, it remains unclear how increased levels of 5-HT
      could contribute to the development of cardiac hypertrophy. Availability of 5-HT
      depends on the mitochondrial enzyme monoamine oxidase A (MAO-A). Therefore, we
      investigated the consequences of MAO-A deletion on ventricular remodeling in the
      model of aortic banding in mice. At baseline, MAO-A deletion was associated with
      an increase in whole blood 5-HT (39.4+/-1.9 microM vs. 24.0+/-0.9 microM in KO
      and WT mice, respectively). Cardiac 5-HT(2A), but not 5-HT(2B) receptors were
      overexpressed in MAO-A KO mice, as demonstrated by real-time PCR and Western-blot
      experiments. After aortic banding, MAO-A KO mice demonstrated greater increase in
      heart wall thickness, heart to body weight ratios, cardiomyocyte cross-section
      areas, and myocardial fibrosis compared to WT. Exacerbation of hypertrophy in KO
      mice was associated with increased amounts of 5-HT in the heart. In order to
      determine the role of 5-HT and 5-HT(2A) receptors in ventricular remodeling in
      MAO-A KO mice, we administered the 5-HT(2A) receptor antagonists ketanserin (1
      mg/kg/day) or M100907 (0.1 mg/kg/day) during 4 weeks of aortic banding. Chronic
      administration of these antagonists strongly prevented exacerbation of
      ventricular hypertrophy in MAO-A KO mice. These results show for the first time
      that regulation of peripheral 5-HT by MAO-A plays a role in ventricular
      remodeling via activation of 5-HT(2A) receptors.

PMID- 19162039
TI  - Hepatoma-derived growth factor represses SET and MYND domain containing 1 gene
      expression through interaction with C-terminal binding protein.
AB  - Hepatoma-derived growth factor (HDGF) is a nuclear protein with both mitogenic
      and angiogenic activity that is highly expressed in the developing heart and
      vasculature. To date, the mechanism underlying the function of HDGF is unknown.
      Oligonucleotide microarray analysis was used to gain insights into HDGF function.
      Adenoviral expression of HDGF significantly (> or =2-fold) downregulated a large
      group (66) of genes, and increased expression of a relatively small number of
      genes (9). Two groups of target genes that are involved in cardiovascular
      development and transcriptional regulation, including the skeletal/cardiac muscle
      specific SET and MYND domain containing 1 (SMYD1) gene, were validated by real
      time PCR. This suggested that HDGF could function as a transcriptional repressor.
      In a one-hybrid system, GBD-HDGF significantly repressed reporter gene activity
      in a dose-dependent manner. This demonstrated that HDGF has transcriptional
      repressive activity. Moreover, in G-7 myoblast cells, over-expression of a GFP
      HDGF fusion specifically downregulated SMYD1 mRNA expression and the activity of
      the human SMYD1 promoter. HDGF repressed SMYD1 gene transcription through
      interaction with a transcriptional corepressor C-terminal binding protein (CtBP).
      Over-expression of CtBP potentiated the trans-repressive activity of HDGF; on the
      other hand, knocking down CtBP attenuated the trans-repressive effect of HDGF.
      HDGF binds CtBP through a non-canonical binding motif (PKDLF) within the PWWP
      domain, as mutation of DL to AS abolished HDGF and CtBP interaction, and
      diminished the trans-repressive effect of HDGF without affecting DNA binding.
      Finally, fluorescent microscopy showed that HDGF induced the nuclear accumulation
      of CtBP, suggesting that HDGF forms a transcriptional complex with CtBP. Taken
      together, our data demonstrate that HDGF functions as a transcriptional repressor
      of the SMYD1 gene through interaction with the transcriptional corepressor CtBP.
      Because of moderate conservation of the CtBP binding motif in HDGF family
      members, trans-repressive activity mediated by CtBP may be a common function
      among HDGF proteins.

PMID- 19162040
TI  - Proteasomes can degrade a significant proportion of cellular proteins independent
      of ubiquitination.
AB  - The critical role of the ubiquitin-26S proteasome system in regulation of protein
      homeostasis in eukaryotes is well established. In contrast, the impact of the
      ubiquitin-independent proteolytic activity of proteasomes is poorly understood.
      Through biochemical analysis of mammalian lysates, we find that the 20S
      proteasome, latent in peptide hydrolysis, specifically cleaves more than 20% of
      all cellular proteins. Thirty intrinsic proteasome substrates (IPSs) were
      identified and in vitro studies of their processing revealed that cleavage occurs
      at disordered regions, generating stable products encompassing structured
      domains. The mechanism of IPS recognition is remarkably well conserved in the
      eukaryotic kingdom, as mammalian and yeast 20S proteasomes exhibit the same
      target specificity. Further, 26S proteasomes specifically recognize and cleave
      IPSs at similar sites, independent of ubiquitination, suggesting that disordered
      regions likely constitute the universal structural signal for IPS proteolysis by
      proteasomes. Finally, we show that proteasomes contribute to physiological
      regulation of IPS levels in living cells and the inactivation of ubiquitin
      activating enzyme E1 does not prevent IPS degradation. Collectively, these
      findings suggest a significant contribution of the ubiquitin-independent
      proteasome degradation pathway to the regulation of protein homeostasis in
      eukaryotes.

PMID- 19162042
TI  - Attenuation of diabetic nephropathy by tocotrienol: involvement of NFkB signaling
      pathway.
AB  - AIM: Diabetic nephropathy is a serious complication for patients with diabetes
      mellitus. Approximately 30-40% of patients with type I and 15% with type II
      diabetes mellitus develop end stage renal disease. The study was designed to
      evaluate the impact of tocotrienol on renal function and reno-inflammatory
      cascade in streptozotocin-induced diabetes. MAIN METHODS: Streptozotocin (STZ)
      induced diabetic rats were treated with tocotrienol (25, 50 and 100 mg/kg), alpha
      tocopherol (100 mg/kg) or with vehicle form 5th to 8th weeks. After 8 weeks,
      urine albumin excretion, urine output, serum creatinine, blood urea nitrogen,
      creatinine and urea clearance were measured. Cytoplasmic and nuclear fractions of
      kidney was prepared for the quantification of oxidative-nitrosative stress (lipid
      peroxidation, superoxide dismutase, catalase, non protein thiols, total nitric
      oxide), tumor necrosis factor-alpha (TNF-alpha), tissue growth factor-1beta (TGF
      beta1), p65 subunit of NFkappabeta and caspase-3. KEY FINDINGS: After 8 weeks of
      STZ injection, the rats produced significant alteration in renal function,
      increased oxidative-nitrosative stress, TNF-alpha, TGF-beta1, caspase-3 activity
      in cytoplasmic lysate and active p65 subunit of NFkappabeta in nuclear lysate of
      kidney of diabetic rats. Interestingly, co-administration of tocotrienol
      significantly and dose-dependently prevented biochemical and molecular changes
      associated with diabetes. Tocotrienol (100 mg/kg) was demonstrated to be more
      effective than alpha-tocopherol (100 mg/kg). Moreover, diabetic rats treated with
      insulin-tocotrienol combination produced more pronounced effect on molecular
      parameters as compared to their respective groups. SIGNIFICANCE: Taken together,
      the data reveal that tocotrienol modulates the release of profibrotic cytokines,
      oxidative stress, ongoing chronic inflammation and apoptosis and thus exerts a
      marked renoprotective effect.

PMID- 19162041
TI  - The sequence dependence of human nucleotide excision repair efficiencies of
      benzo[a]pyrene-derived DNA lesions: insights into the structural factors that
      favor dual incisions.
AB  - Nucleotide excision repair (NER) is a vital cellular defense system against
      carcinogen-DNA adducts, which, if not repaired, can initiate cancer development.
      The structural features of bulky DNA lesions that account for differences in NER
      efficiencies in mammalian cells are not well understood. In vivo, the predominant
      DNA adduct derived from metabolically activated benzo[a]pyrene (BP), a prominent
      environmental carcinogen, is the 10S (+)-trans-anti-[BP]-N(2)-dG adduct (G*),
      which resides in the B-DNA minor groove 5'-oriented along the modified strand. We
      have compared the structural distortions in double-stranded DNA, imposed by this
      adduct, in the different sequence contexts 5'-...CGG*C..., 5'-...CG*GC..., 5'
      ...CIG*C... (I is 2'-deoxyinosine), and 5'-...CG*C.... On the basis of
      electrophoretic mobilities, all duplexes manifest moderate bends, except the 5'
      ...CGG*C...duplex, which exhibits an anomalous, slow mobility attributed to a
      pronounced flexible kink at the site of the lesion. This kink, resulting from
      steric hindrance between the 5'-flanking guanine amino group and the BP aromatic
      rings, both positioned in the minor groove, is abolished in the 5'
      ...CIG*C...duplex (the 2'-deoxyinosine group, I, lacks this amino group). In
      contrast, the sequence-isomeric 5'-...CG*GC...duplex exhibits only a moderate
      bend, but displays a remarkably increased opening rate at the 5'-flanking base
      pair of G*, indicating a significant destabilization of Watson-Crick hydrogen
      bonding. The NER dual incision product yields were compared for these different
      sequences embedded in otherwise identical 135-mer duplexes in cell-free human
      HeLa extracts. The yields of excision products varied by a factor of as much as
      approximately 4 in the order 5'-...CG*GC...>5'...CGG*C...>or=5'...CIG*C...>or=5'
      ...CG*C.... Overall, destabilized Watson-Crick hydrogen bonding, manifested in
      the 5'-...CG*GC...duplex, elicits the most significant NER response, while the
      flexible kink displayed in the sequence-isomeric 5'-...CGG*C...duplex represents
      a less significant signal in this series of substrates. These results demonstrate
      that the identical lesion can be repaired with markedly variable efficiency in
      different local sequence contexts that differentially alter the structural
      features of the DNA duplex around the lesion site.

PMID- 19162043
TI  - Mevinolin enhances osteogenic genes (ALP, type I collagen and osteocalcin), CD44,
      CD47 and CD51 expression during osteogenic differentiation.
AB  - AIMS: In this study, we evaluated the effect of mevinolin on the expressions of
      osteogenic genes and surface molecules expression during osteogenesis. MAIN
      METHODS: D1 cells were cultured in osteogenic differentiation medium (ODM) for 6
      days, treated with mevinolin for 2 days, and then subjected to alizarin red S
      staining, MTT assays, alkaline phosphatase (ALP) activity determinations, energy
      dispersive X-ray spectrophotometry (EDX), real-time PCR, Western blot,
      fluorescence microscopy and FACS analysis. KEY FINDINGS: Mevinolin is commonly
      prescribed and widely used to lower cholesterol levels, and offers an important,
      effective approach to the treatment of hypercholesterolemia and arteriosclerosis.
      However, the direct effect of mevinolin on osteogenesis in vitro has not been
      clarified. ODM has been previously shown to increase the osteoblast
      differentiation of D1 cells. In the present study, we investigated the
      expressions of osteogenic genes and surface molecules during osteoblast
      differentiation induced by mevinolin. We found that the induction of ALP, type I
      collagen, osteocalcin, CD44, CD47 and CD51 by mevinolin is responsible for the
      osteoblastic differentiation of D1 cells. SIGNIFICANCE: Our data show that
      mevinolin enhances the expressions of proteins and surface molecules related to
      osteogenesis.

PMID- 19162044
TI  - Discontinuity induced bifurcations in a model of Saccharomyces cerevisiae.
AB  - We perform a bifurcation analysis of the mathematical model of Jones and Kompala
      [K.D. Jones, D.S. Kompala, Cybernetic model of the growth dynamics of
      Saccharomyces cerevisiae in batch and continuous cultures, J. Biotechnol. 71
      (1999) 105-131]. Stable oscillations arise via Andronov-Hopf bifurcations and
      exist for intermediate values of the dilution rate as has been noted from
      experiments previously. A variety of discontinuity induced bifurcations arise
      from a lack of global differentiability. We identify and classify discontinuous
      bifurcations including several codimension-two scenarios. Bifurcation diagrams
      are explained by a general unfolding of these singularities.

PMID- 19162045
TI  - The aldo-keto reductase AKR1C3 contributes to 7,12-dimethylbenz(a)anthracene-3,4
      dihydrodiol mediated oxidative DNA damage in myeloid cells: implications for
      leukemogenesis.
AB  - The aldo-keto reductase AKR1C3, has been shown to regulate myelopoiesis via its
      ability to metabolise prostaglandin D2 (PGD2). Other studies have demonstrated
      the oxidative activation of polycyclic aromatic hydrocarbon (PAH) procarcinogens
      by AKR1C3 in cell-free systems. This is the first study that addresses whether
      AKR1C3 mediates carcinogen activation within intact living cells following
      manipulation of AKR1C3 by molecular intervention. Quantitative RT-PCR identified
      AKR1C3 as the predominant AKR1C isoform expressed in acute myeloid leukemia
      (AML). Exposure of K562 and KG1a myeloid cell lines to the known AKR1C3 substrate
      7,12-dimethylbenz(a)anthracene-3,4-dihydrodiol (7,12-DMBA-3,4-diol) resulted in
      both single strand DNA breaks and oxidative DNA damage as measured using
      conventional and FPG-modified comet assays respectively. PGD2-keto reductase
      activity was shown to be correlated with relative AKR1C3 expression and together
      with quantitative real time PCR was used to validate the RNAi-knockdown of AKR1C3
      in K562 cells. Knockdown of AKR1C3 did not alter single strand DNA breaks
      following 7,12-DMBA-3,4-diol exposure but significantly decreased oxidative DNA
      damage. A similar interrelationship between AKR1C3 activity and 7,12-DMBA-3,4
      diol mediated oxidative DNA damage but not single strand breaks was observed in
      KG1a cells. Finally, AKR1C3 knockdown also resulted in spontaneous erythroid
      differentiation of K562 cells. Since K562 cells are a model of AML blast crisis
      of chronic myeloid leukemia (CML) the data presented here identify AKR1C3 as a
      novel mediator of carcinogen-induced initiation of leukemia, as a novel regulator
      of erythroid differentiation and paradoxically as a potential new target in the
      treatment of CML.

PMID- 19162046
TI  - Alterations of N/OFQ and NOP receptor gene expression in the substantia nigra and
      caudate putamen of MPP+ and 6-OHDA lesioned rats.
AB  - It has been suggested that the opioid-like neuropeptide nociceptin/orphanin
      FQ(N/OFQ) and its receptor (NOPr) may contribute to Parkinson's disease. Based on
      this idea, the aim of our study was to investigate the involvement of the N/OFQ
      NOPr system in an animal model of Parkinson's disease and to evaluate if this
      neuropeptidergic system is acting through mechanisms involving glutamate and/or
      GABA. We injected the neurotoxins MPP+ or 6-OHDA into the cerebral ventricles and
      10 days later measured N/OFQ and NOPr gene expression in caudate putamen (CP) and
      substantia nigra (SN), by RT-PCR. A large reduction in N/OFQ and NOPr mRNAs was
      observed in the CP of rat treated with either MPP+ or 6-OHDA, MPP+ being more
      effective than 6-OHDA. Both the neurotoxins induced an increase in N/OFQ gene
      expression in the SN, but only MPP+ evoked a significant down-regulation of NOPr
      in this area, showing a slight trend of reduction in 6-OHDA treated rats.
      Moreover, a reduction in the levels of glutamic acid decarboxylase (GAD65/67), an
      enzyme that converts the excitatory neurotransmitter glutamate to the inhibitory
      neurotransmitter y-aminobutyric acid (GABA), was also observed in the SN
      following 6-OHDA. These data suggest that DA modulates N/OFQ-NOPr system gene
      expression in SN and CP, strengthening the hypothesis that this neuropeptidergic
      system could be implicated in the mechanisms underlying Parkinson's disease. Our
      data might also suggest that the GABAergic system plays a role in the regulation
      of nigral function, although further studies are necessary to confirm this
      hypothesis. In agreement with previous studies, we also support the hypothesis of
      a potential value for NOP receptor antagonists to attenuate symptoms related to
      the degeneration of nigrostriatal dopaminergic pathway.

PMID- 19162047
TI  - Allosteric modulation of metabotropic glutamate receptor 5 affects
      phosphorylation, internalization, and desensitization of the micro-opioid
      receptor.
AB  - Recent evidence suggests that opioid analgesia and tolerance can be modulated by
      metabotropic glutamate receptors. Therefore, we studied the functional coupling
      and desensitization of the micro-opioid receptor (MOR) in human embryonic kidney
      (HEK) 293 cells which co-express metabotropic glutamate receptor 5 (mGluR5). As
      demonstrated by the D-Ala2,N-MePhe4,Gl-ol5-enkephalin (DAMGO)-induced inhibition
      of intracellular cAMP level and by binding studies, the co-expression of mGluR5
      had no substantial effect on the agonist binding sites and functional coupling of
      the MOR. However, in MOR/ mGluR5 co-expressing cells, the non-competitive mGluR5
      antagonist MPEP (2-methyl-6-(phenyl-ethynyl)-pyridine) decreases the DAMGO
      induced MOR phosphorylation, internalization, and desensitization, whereas non
      selective competitive mGluR antagonists or agonists had no effects. These
      findings indicate that an allosteric modulation of mGluR5 can affect the agonist
      induced MOR signalling and regulation. As a mechanistic basis for the observed
      effects we suggested an interaction/heterodimerization of MOR and mGluR5, which
      is supported by the DAMGO-induced co-internalization of MOR and mGluR5 and by the
      increase of MPEP binding sites (Bmax) and a change of the binding affinity (K(D))
      of mGluR5 receptors after the co-expression of MOR. In addition, co
      immunoprecipitation experiments revealed evidence for an interaction between MOR
      and mGluR5 which is facilitated by MPEP treatment.

PMID- 19162048
TI  - Predicting judged similarity of natural categories from their neural
      representations.
AB  - We report a combined behavioral and functional magnetic resonance imaging (fMRI)
      study of conceptual similarity among members of a natural category (mammals). The
      study examined the relationship between computed pairwise similarity of neural
      responses to viewed mammals (e.g. bear, camel, dolphin) and subjective pairwise
      similarity ratings of the same set of mammals, obtained from subjects after the
      scanning session. In each functional region of interest (fROI), measures of
      neural similarity were compared to behavioral ratings. fROIs were identified as
      clusters of voxels that discriminated intact versus scrambled images of mammals
      (no information about similarity was used to define fROIs). Neural similarity was
      well correlated with behavioral ratings in fROIs covering the lateral occipital
      complex in both hemispheres (with overlap of the fusiform and inferior temporal
      gyri on the right side). The latter fROIs showed greater hemodynamic response to
      intact versus scrambled images of mammals whereas the fROIs that failed to
      predict similarity showed the reverse pattern. The findings provide novel
      evidence that information about the fine structure of natural categories is
      coarsely coded in regions of the ventral visual pathway. Implications for the
      theory of inductive inference are discussed.

PMID- 19162049
TI  - Perseveration and contrast effects in grasping.
AB  - In order to assess sequential effects in grasping a disc, grip aperture was
      measured as a function of whether the previous disc was smaller or larger than
      the current target. In Experiment 1, a biphasic sequential effect was found over
      the course of the reach: Early in the movement, a contrast effect was observed in
      which grip aperture was wider following a smaller target; later in the movement,
      a perseveration effect was observed in which grip aperture was smaller following
      a smaller target. In Experiment 2, the target was accompanied by context discs
      that were larger and smaller than the range of target sizes. In this case, there
      was no contrast effect, and a perseveration effect was observed over the course
      of the movement trajectory. In a third experiment, a sequential contrast effect
      was found when subjects did not grasp the disc but merely estimated its size. Our
      interpretation is that there are two mechanisms producing sequential effects: a
      perceptual contrast effect in which the target appears larger following a smaller
      disc, and a motor perseveration effect in which subjects tend to reuse similar
      motor control parameters from trial to trial. These effects were overlaid in
      Experiment 1, producing the observed biphasic response. However, in Experiment 2,
      the context eliminated sequential perceptual contrast, and grip aperture only
      showed an effect of perseveration. In Experiment 3, only the perceptual effect
      was found because subjects did not need to grasp the disc.

PMID- 19162050
TI  - Effects of sentence context on lexical ambiguity resolution in patients with
      schizophrenia.
AB  - Previous research has suggested that a failure in processing contextual
      information may account for the heterogeneous clinical manifestations and
      cognitive impairments observed in schizophrenia. In the domain of language,
      context processing in schizophrenia has been investigated mostly with single-word
      semantic priming paradigms; however, natural language comprehension depends on
      more than semantic relations between words. The present study aimed to
      systematically assess sentence context effects in homonym meaning activation in
      patients with schizophrenia. Fourteen patients with schizophrenia and 14 normal
      controls matched to the patients on sex, age, education and parental education,
      were examined using a cross-modal priming paradigm. Primes were sentences biasing
      the first, second, or neither meaning of a sentence-final equibiased homonym;
      targets were related to either the first or the second meaning of the homonym and
      appeared after an interstimulus interval (ISI) of 0ms or 750ms. Patients with
      schizophrenia exhibited a trend towards facilitation of both target types
      following unbiased sentences at ISI=0ms, similar to controls. However, in
      contrast to the pattern of selective target facilitation exhibited by control
      subjects following first- or second meaning-biased sentences, no significant
      target facilitation was observed in patients in the same condition. At ISI=750ms,
      patients did no longer exhibit significant target facilitation in any sentence
      context condition. This pattern of results is compatible with the assumption of a
      combined impairment in lexical (automatic spreading of activation within the
      semantic network) and extralexical (working memory) processes in patients with
      schizophrenia.

PMID- 19162051
TI  - The association between semantic dementia and surface dyslexia in Japanese.
AB  - One theory about reading suggests that producing the correct pronunciations of
      written words, particularly less familiar words with an atypical spelling-sound
      relationship, relies in part on knowledge of the word's meaning. This hypothesis
      has been supported by reports of surface dyslexia in large case-series studies of
      English-speaking/reading patients with semantic dementia (SD), but would have
      increased credibility if it applied to other languages and writing systems as
      well. The hypothesis predicts that, of the two systems used to write Japanese, SD
      patients should be unimpaired at oral reading of kana because of its invariant
      relationship between orthography and phonology. By contrast, oral reading of
      kanji should be impaired in a graded fashion depending on the consistency
      characteristics of the kanji target words, with worst performance on words whose
      component characters take 'minority' (atypical) pronunciations, especially if the
      words are of lower frequency. Errors in kanji reading should primarily reflect
      assignment of more typical readings to the component characters in these atypical
      words. In the largest-ever-reported case series of Japanese patients with
      semantic dementia, we tested and confirmed this hypothesis.

PMID- 19162052
TI  - The role of spectral and durational properties on hemispheric asymmetries in
      vowel perception.
AB  - The aim of the current study is to investigate potential hemispheric asymmetries
      in the perception of vowels and the influence of different time scales on such
      asymmetries. Activation patterns for naturally produced vowels were examined at
      three durations encompassing a short (75 ms), medium (150 ms), and long (300 ms)
      integration time window in a discrimination task. A set of 5 corresponding non
      speech sine wave tones were created with frequencies matching the second formant
      of each vowel. Consistent with earlier hypotheses, there was a right hemisphere
      preference in the superior temporal gyrus for the processing of spectral
      information for both vowel and tone stimuli. However, observed laterality
      differences for vowels and tones were a function of heightened right hemisphere
      sensitivity to long integration windows, whereas the left hemisphere showed
      sensitivity to both long and short integration windows. Although there were a
      number of similarities in the processing of vowels and tones, differences also
      emerged suggesting that even fairly early in the processing stream at the level
      of the STG, different mechanisms are recruited for processing vowels and tones.

PMID- 19162053
TI  - An unexpected reduction in sucrose concentration activates the HPA axis on
      successive post shift days without attenuation by discriminative contextual
      stimuli.
AB  - Previous studies have shown that the successive negative contrast procedure, in
      which food-restricted rats entrained to once daily, brief presentations of 32%
      sucrose are unexpectedly shifted to a 4% solution, results in an adrenocortical
      response on the second, but not the first postshift day. We attempted to
      generalize that finding in our own procedure. In Experiment 1, two groups of rats
      were given a 32% sucrose solution once daily in their home cages for 14 days
      before being shifted to a 4% solution. One group was killed 10 min after the
      first 4% solution and one was killed after the second 4% solution. In addition,
      two groups receiving either 32% or 4% sucrose throughout the experiment served as
      unshifted controls. In contrast to previous findings, both shifted groups
      exhibited prominent adrenocorticotropin hormone (ACTH) and adrenocortical (B)
      responses on both postshift days compared to unshifted controls, which did not
      differ from one another. Experiment 2a employed distinctive contexts to test if
      the lack of generality of the delayed HPA axis response was due to suppressive
      effects of S(+) on the first postshift day. Rats were given once daily 32%
      sucrose in S(+) and equal exposure time in S(-). Half of these rats were shifted
      to 4% sucrose in S(+) and half were shifted in S(-). These two groups were
      compared to home cage controls. Half of each group was killed after their first
      4% sucrose, and half after the second 4% sucrose. All rats showed ACTH and B
      responses comparable to shifted rats in Experiment 1. S(+) failed to suppress the
      HPA axis, and the stress response was higher on the first compared to the second
      day of the shift. Experiment 2b established that distinctive contexts predicting
      sucrose, S(+), or not predicting sucrose, S(-), controlled behavioral choice and
      contextual discrimination. Thus, there was no evidence that issues of stimulus
      control could explain the lack of generality of previous findings. The data
      indicate that thwarting sucrose expectancies is stressful, and that this stress
      response habituates across days.

PMID- 19162054
TI  - Long-term behavioral consequences of prenatal MDMA exposure.
AB  - The current study sought to determine whether prenatal 3,4-methylenedioxy-N
      methamphetamine (MDMA) exposure from E14-20 in the rat resulted in behavioral
      sequelae in adult offspring. Prenatal MDMA exposure results in increased
      dopaminergic fiber density in the prefrontal cortex, striatum and nucleus
      accumbens of young rats. Since these areas are critical in response to novelty,
      reward, attention and locomotor activity, we hypothesized that prenatal MDMA
      exposure would produce significant changes in the performance of tasks that
      examine such behaviors in adult rats. Adult rats prenatally exposed to MDMA
      exhibited greater activity and spent more time in the center during a novel open
      field test as compared to controls. This increased activity was not reflected in
      normal home cage activity. Prenatal exposure to MDMA did not affect feeding or
      food reward. It did not alter cocaine self-administration behaviors, nor did it
      have an effect on the locomotor response to amphetamine challenge. Finally, while
      prenatal MDMA did not affect performance in the radial arm maze or the Morris
      water maze (MWM), these animals demonstrated altered performance in a cued MWM
      paradigm. Prenatal MDMA exposure resulted in perseverative attendance to a
      hanging cue when the platform in the MWM was removed as compared to controls.
      Together, these data demonstrate that prenatal exposure to MDMA results in a
      behavioral phenotype in adult rats characterized by reduced anxiety, a heightened
      response to novelty, and "hyperattentiveness" to environmental cues during
      spatial learning.

PMID- 19162056
TI  - Chest staining variation as a signal of testosterone levels in male Verreaux's
      Sifaka.
AB  - Male Verreaux's sifaka (Propithecus verreauxi) exhibit variation in the staining
      of chest hair in association with the activity of the sternal gland. Scent
      marking behavior and social relationships have been shown to vary with the state
      of chest staining. Research on other mammals suggests that sternal gland activity
      is modulated by testosterone. The goal of this study was to examine the
      relationship among fecal testosterone, testes mass, and chest staining in sifaka.
      I predicted that for sifaka (1) testosterone and testes mass are positively
      correlated, (2) stained males have higher testosterone and larger testes than
      clean-chested males, (3) testes mass is greater during the mating season than the
      birth season, and (4) testes mass is comparable to species with multimale mating
      systems. Eighty fecal samples were collected from eight adult males in five
      social groups in the Kirindy Mitea National Park of Madagascar during the mating
      season and analyzed using enzyme immunoassays. Males were captured during the
      mating season and the subsequent birth season to measure body mass and testes
      size and to document chest staining. Stained males had significantly higher fT
      and larger testes mass than clean-chested males. Testes mass was significantly
      greater during the mating season than the birth season for all males. However,
      the stained males exhibited less testes mass reduction during birth season than
      clean-chested males. These results suggest that the activity of the sternal gland
      is regulated by testosterone and that sexual selection has shaped male
      morphological variation in Verreaux's sifaka.

PMID- 19162057
TI  - Development of a highly sensitive ELISA for aldosterone in mouse urine:
      validation in physiological and pathophysiological states of aldosterone excess
      and depletion.
AB  - BACKGROUND: Clinical studies have established aldosterone as a critical
      physiological and pathophysiological factor in salt and water homeostasis, blood
      pressure control and in heart failure. Genetic and physiological studies of mice
      are used to model these processes. A sensitive and specific assay for aldosterone
      is therefore needed to monitor adrenocortical activity in murine studies of renal
      function and cardiovascular diseases. METHODS: Antibodies against aldosterone
      were raised in sheep as previously described. HRP-Donkey-anti-sheep IgG enzyme
      tracer was produced in our laboratory using the Lightning-Link HRP technique.
      Aldosterone ELISA protocol was validated and optimised to achieve the best
      sensitivity. The assay was validated by analysing the urine of mice collected
      under various experimental conditions designed to stimulate or suppress
      aldosterone in the presence of other potentially interfering steroid hormones.
      RESULTS: Cross-reactivity with the steroids most likely to interfere was minimal:
      corticosterone=0.0028%, cortisol=0.0006%, DOC=0.0048% except for 5alpha-dihydro
      aldosterone=1.65%. Minimum detection limit of this ELISA was 5.2 pmole/L (1.5
      pg/mL). The validity of urinary aldosterone ELISA was confirmed by the excellent
      correlation between results obtained before and after solvent extraction and HPLC
      separation step (Y=1.092X+0.03, R(2)=0.995, n=54). Accuracy studies, parallelism
      and imprecision data were determined and all found to be satisfactory. Using this
      assay, mean urinary aldosterone levels were (i) approximately 60-fold higher in
      females than males mice; (ii) increased 6-fold by dietary sodium restriction;
      (iii) increased 10-fold by ACTH infusion and (iv) reduced by >60% in Cyp11b1 null
      mice. CONCLUSION: We describe an ELISA for urinary aldosterone that is suitable
      for repeated non-invasive measurements in mice. Female aldosterone levels are
      higher than males. Unlike humans, most aldosterone in mouse urine is not
      conjugated. Increased levels were noted in response to dietary sodium restriction
      and ACTH treatment. The sensitivity of the assay is sufficient to detect
      suppressed levels in mouse models of congenital adrenal hyperplasia.

PMID- 19162055
TI  - Nitric oxide and ERK/MAPK mediation of estrous behavior induced by GnRH, PGE2 and
      db-cAMP in rats.
AB  - We tested the hypothesis that GnRH, PGE2 and db-cAMP act via the nitric oxide
      (NO)-cGMP and MAPK pathways to facilitate estrous behavior (lordosis and
      proceptivity) in estradiol-primed female rats. Estradiol-primed rats received
      intracerebroventricular (icv) infusions of pharmacological antagonists of NO
      synthase (L-NAME), NO-dependent soluble guanylyl cyclase (ODQ), protein kinase G
      (KT5823), or the ERK1/2 inhibitor PD98059 15 min before icv administration of 50
      ng of GnRH, 1 microg of PGE2 or 1 microg of db-cAMP. Icv infusions of GnRH, PGE2
      and db-cAMP enhanced estrous behavior at 1 and 2 h after drug administration.
      Both L-NAME and ODQ blocked the estrous behavior induced by GnRH, PGE2 and db
      cAMP at some of the times tested. The protein kinase G inhibitor KT5823 reduced
      PGE2 and db-cAMP facilitation of estrous behavior but did not affect the
      behavioral response to GnRH. In contrast, PD98059 blocked the estrous behavior
      induced by all three compounds. These data support the hypothesis that the NO
      cGMP and ERK/MAPK pathways are involved in the lordosis and proceptive behaviors
      induced by GnRH, PGE2 and db-cAMP. However, cGMP mediation of GnRH-facilitated
      estrous behavior is independent of protein kinase G.

PMID- 19162058
TI  - Genomic and non-genomic effect of cortisol on phagocytosis in freshwater teleost
      Channa punctatus: an in vitro study.
AB  - The non-genomic action of glucocorticoid, besides classical genomic action, is
      recently implicated in regulation of phagocyte activities in mammals. With regard
      to the non-mammalian vertebrates, this study in the teleost, Channa punctatus,
      for the first time demonstrates the regulation of innate immunity by cortisol
      following non-genomic pathway. Cortisol suppressed the phagocytic activity of
      splenic phagocytes in a time- and concentration-dependent manner. Intriguingly,
      it impeded the phagocytosis within 15 min which is too short for conventional
      genomic action. The cortisol-induced rapid inhibition could not be altered by
      transcription and translation inhibitors, suggesting the involvement of non
      genomic pathway. Since membrane impermeable BSA-cortisol mimicked the rapid
      inhibitory effect of cortisol at 15 min, we speculated that cortisol exerted its
      non-genomic effect on phagocytosis by acting at membrane site. These membrane
      bound glucocorticoid receptors seem similar to cytosolic GR, as rapid inhibitory
      effect of cortisol was blocked by the cytoplasmic glucocorticoid receptor blocker
      RU-486. Using inhibitors for adenylate cyclase/protein kinase A (PKA) and
      estimating intracellular cAMP, adenylate cyclase-PKA pathway was seen involved in
      mediating the rapid non-genomic action of cortisol in phagocytes of C. punctatus.
      In contrast to the rapid effect, inhibitory effect of cortisol on phagocytosis
      after 1h was blocked by protein synthesis inhibitors, thus implicating genomic
      regulation. An overview of our data suggests that cortisol regulates phagocytosis
      in C. punctatus via genomic as well as non-genomic mechanisms. Further, the non
      genomic action of cortisol is mediated via membrane-bound GR coupled to cAMP-PKA
      system.

PMID- 19162059
TI  - Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles.
AB  - In general, gold nanoparticles are recognized as being as nontoxic. Still, there
      have been some reports on their toxicity, which has been shown to depend on the
      physical dimension, surface chemistry, and shape of the nanoparticles. In this
      study, we carry out an in vivo toxicity study using 13 nm-sized gold
      nanoparticles coated with PEG (MW 5000). In our findings the 13 nm sized PEG
      coated gold nanoparticles were seen to induce acute inflammation and apoptosis in
      the liver. These nanoparticles were found to accumulate in the liver and spleen
      for up to 7 days after injection and to have long blood circulation times. In
      addition, transmission electron microscopy showed that numerous cytoplasmic
      vesicles and lysosomes of liver Kupffer cells and spleen macrophages contained
      the PEG-coated gold nanoparticles. These findings of toxicity and kinetics of PEG
      coated gold nanoparticles may have important clinical implications regarding the
      safety issue as PEG-coated gold nanoparticles are widely used in biomedical
      applications.

PMID- 19162060
TI  - A model of non-linear interactions between cortical top-down and horizontal
      connections explains the attentional gating of collinear facilitation.
AB  - Past physiological and psychophysical experiments have shown that attention can
      modulate the effects of contextual information appearing outside the classical
      receptive field of a cortical neuron. Specifically, it has been suggested that
      attention, operating via cortical feedback connections, gates the effects of long
      range horizontal connections underlying collinear facilitation in cortical area
      V1. This article proposes a novel mechanism, based on the computations performed
      within the dendrites of cortical pyramidal cells, that can account for these
      observations. Furthermore, it is shown that the top-down gating signal into V1
      can result from a process of biased competition occurring in extrastriate cortex.
      A model based on these two assumptions is used to replicate the results of
      physiological and psychophysical experiments on collinear facilitation and
      attentional modulation.

PMID- 19162061
TI  - Activation of Akt by lithium: pro-survival pathways in aging.
AB  - The effects of lithium on senescence were investigated using the senescence
      accelerated mouse prone 8 (SAMP8) mice and cultures of aging cerebellar granule
      cells. Our in vitro findings, using cerebellar granule neurons, demonstrate that
      lithium (1-10mM) exerts neuroprotective effects in young cultures (7-8 days)
      against LY294002-induced Akt inhibition. Furthermore, lithium (10mM) inhibits GSK
      3beta activity by upregulating p-GSK-3beta (ser-9) and increases p-FOXO1 (Ser256)
      suggesting an effective anti-apoptotic effect. Our data also showed that lithium
      in aged cultures exerts anti-apoptotic effects via Akt activation and consequent
      inhibition of downstream targets regulated by this enzyme. Finally, the
      administration of lithium to senescence-accelerated mice (SAMP8) and senescence
      accelerated resistant mice (SAMR1) at 3 months of age also caused increased Akt
      activity and p-FoxO-1. These results demonstrate the effectiveness of lithium in
      preventing age-related neural loss and the potential therapeutic applications of
      lithium in treatment/prevention of neurological disease.

PMID- 19162062
TI  - Identification of novel VHL regulated genes by transcriptomic analysis of RCC10
      renal carcinoma cells.

PMID- 19162063
TI  - Collagen VI myopathies: from the animal model to the clinical trial.

PMID- 19162064
TI  - Working for health? Evidence from systematic reviews on the effects on health and
      health inequalities of organisational changes to the psychosocial work
      environment.
AB  - OBJECTIVE: To map the health effects of interventions which aim to alter the
      psychosocial work environment, with a particular focus on differential impacts by
      socio-economic status, gender, ethnicity, or age. METHODS: A systematic approach
      was used to identify, appraise and summarise existing systematic reviews
      (umbrella review) that examined the health effects of changes to the psychosocial
      work environment. Electronic databases, websites, and bibliographies, were
      searched from 2000-2007. Experts were also contacted. Identified reviews were
      critically appraised and the results summarised taking into account
      methodological quality. The review was conducted in the UK between October 2006
      and December 2007. RESULTS: Seven systematic reviews were identified. Changes to
      the psychosocial work environment were found to have important and generally
      beneficial effects on health. Importantly, five reviews suggested that
      organisational level psychosocial workplace interventions may have the potential
      to reduce health inequalities amongst employees. CONCLUSION: Policy makers should
      consider organisational level changes to the psychosocial work environment when
      seeking to improve the health of the working age population.

PMID- 19162065
TI  - Trends in the prevalence of obesity in employed adults in central-western France:
      a population-based study, 1995-2005.
AB  - OBJECTIVE: The overall trend of obesity prevalence has increased during the last
      decades, even in France which has one of the lowest prevalence in Europe. The aim
      of this study was to assess, according to socioeconomic status (SES), whether a
      shift in the obesity prevalence trends could be observed since the French
      National Nutrition and Public Health Program was implemented in 2001. METHODS:
      Standardised cross-sectional repeated population-based data from the French
      Social Security Health Examination Centers in the central-western region of
      France (n=339,882). We examined regression slopes (95% CI) of overall and
      abdominal obesity from 1995 to 2005 according to SES. We also compared slopes
      within each SES between 1995-2001 and 2001-2005. RESULTS: After standardisation
      to the French age distribution, 6.9% of men and 6.4% of women were obese in 1995
      and 8.9% and 8.6% in 2005, respectively. Abdominal adiposity concerned 5.6% of
      men and 8.5% of women in 1995 and 9.5% and 14.3% in 2005. Obesity prevalence
      regression slopes between 1995 and 2005 increased in all SES categories, except
      management professionals in both genders and office/service personnel male who
      were stable. Significant regression slopes before 2001 became non-significant
      afterward in office/service personnel males for obesity prevalence; and for
      abdominal obesity in manual workers women and office/service personnel (p=0.05,
      in men). CONCLUSIONS: Our data confirm the overall epidemic rise in the obesity
      prevalence trends during the last decade, except in management professionals and
      office/service personnel men. Obesity prevalence trends in office/service
      personnel and manual workers women for abdominal obesity were also observed to
      stabilise since 2001. We could hypothesize that the National Nutrition and Public
      Health Program may partly be involved in this decreasing trend among
      office/service personnel mainly. Policymakers should take into account these data
      to assess the effectiveness of obesity prevention public-health strategies in the
      future.

PMID- 19162066
TI  - Perception of eating practices and stages of change among Brazilian adolescents.
AB  - OBJECTIVE: To evaluate the perception of eating practices and the stages of
      change among adolescents. METHODS: Cross-sectional study involving a
      representative sample of 390 adolescents from 11 public schools in the city of
      Piracicaba, Brazil, in 2004. Food consumption was identified by a food frequency
      questionnaire and the perception of eating practices evaluation was conducted by
      comparing food consumption and individual classification of healthy aspects of
      the diet. The participants were classified within stages of change by means of a
      specific algorithm. A reclassification within new stages of change was proposed
      to identify adolescents with similar characteristics regarding food consumption
      and perception. RESULTS: Low consumption of fruit and vegetables and high
      consumption of sweets and fats were identified. More than 44% of the adolescents
      had a mistaken perception of their diet. A significant relationship between the
      stages of change and food consumption was observed. The reclassification among
      stages of change, through including the pseudo-maintenance and non-reflective
      action stages was necessary, considering the high proportion of adolescents who
      erroneously classified their diets as healthy. CONCLUSION: Classification of the
      adolescents into stages of change, together with consumption and perception data,
      enabled identification of groups at risk, in accordance with their inadequate
      dietary habits and non-recognition of such habits.

PMID- 19162067
TI  - The human antimicrobial protein psoriasin acts by permeabilization of bacterial
      membranes.
AB  - Psoriasin, a member of the S100 family of calcium-binding proteins (S100A7) is
      highly upregulated in the skin of psoriasis patients. As it has recently been
      found to exhibit antimicrobial activity, an important role of psoriasin in
      surface defence has been suggested. The similarity of the three-dimensional
      structures of psoriasin and amoebapore A, an ancient antimicrobial, pore-forming
      peptide from Entamoeba histolytica, intrigued us to investigate whether the human
      psoriasin is also able to permeabilize bacterial membranes. Here, we demonstrate
      that psoriasin exerts pore-forming activity at pH values below 6 demonstrating
      that disruption of microbial membranes is the basis of its antimicrobial activity
      at low pH. Furthermore, the killing activity of psoriasin shows pH-dependent
      target specificity. At neutral pH, the Gram-negative bacterium E. coli is killed
      apparently without compromising its membrane, whereas at low pH exclusively the
      Gram-positive bacterium B. megaterium is killed by permeabilization of its
      cytoplasmic membrane.

PMID- 19162068
TI  - Molecular stress response in the CNS of mice after systemic exposure to
      interferon-alpha, ionizing radiation and ketamine.
AB  - We previously showed that the expression of troponin T1 (Tnnt 1) was induced in
      the central nervous system (CNS) of adult mice 30min after treatment with
      ketamine, a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist. We
      hypothesized that Tnnt 1 expression may be an early molecular biomarker of stress
      response in the CNS of mice. To further evaluate this hypothesis, we investigated
      the regional expression of Tnnt 1 in the mouse brain using RNA in situ
      hybridization 4h after systemic exposure to interferon-alpha (IFN-alpha) and
      gamma ionizing radiation, both of which have be associated with wide ranges of
      neuropsychiatric complications. Adult B6C3F1 male mice were treated with either
      human IFN-alpha (a single i.p. injection at 1 x 10(5)IU/kg) or whole body gamma
      radiation (10cGy or 2Gy). Patterns of Tnnt 1 transcript expression were compared
      in various CNS regions after IFN-alpha, radiation and ketamine treatments
      (previous study). Tnnt 1 expression was consistently induced in pyramidal neurons
      of cerebral cortex and hippocampus after all treatment regimens including 10cGy
      of ionizing radiation. Regional expression of Tnnt 1 was induced in Purkinje
      cells of cerebellum after ionizing radiation and ketamine treatment; but not
      after IFN-alpha treatment. None of the three treatments induced Tnnt 1 expression
      in glial cells. The patterns of Tnnt 1 expression in pyramidal neurons of
      cerebral cortex and hippocampus, which are both known to play important roles in
      cognitive function, memory and emotion, suggest that the expression of Tnnt 1 may
      be an early molecular biomarker of induced CNS stress.

PMID- 19162069
TI  - Role of voltage-gated calcium channels in ascending pain pathways.
AB  - Voltage gated calcium channels (VGCCs) are well established mediators of pain
      signals in primary afferent neurons. N-type calcium channels are localized to
      synaptic nerve terminals in laminae 1 and 2 of the dorsal horn where their
      opening results in the release of neurotransmitters such as glutamate and
      substance P. The contribution of N-type channels to the processing of pain
      signals is regulated by alternate splicing of the N-type channel gene, with
      unique N-type channel splice variants being expressed in small nociceptive
      neurons. In contrast, T-type VGCCs of the Ca(v)3.2 subtype are likely localized
      to nerve endings where they regulate cellular excitability. Consequently,
      inhibition of N-type and Ca(v)3.2 T-type VGCCs has the propensity to mediate
      analgesia. T-type channel activity is regulated by redox modulation, and can be
      inhibited by a novel class of small organic blockers. N-type VGCC activity can be
      potently inhibited by highly selective peptide toxins that are delivered
      intrathecally, and the search for small organic blockers with clinical efficacy
      is ongoing. Here, we provide a brief overview of recent advances in this area, as
      presented at the Spring Pain Research conference (Grand Cayman, 2008).

PMID- 19162072
TI  - Activity-dependent structural plasticity.
AB  - Plasticity in the brain reaches far beyond a mere changing of synaptic strengths.
      Recent time-lapse imaging in the living brain reveals ongoing structural
      plasticity by forming or breaking of synapses, motile spines, and re-routing of
      axonal branches in the developing and adult brain. Some forms of structural
      plasticity do not follow Hebbian- or anti-Hebbian paradigms of plasticity but
      rather appear to contribute to the homeostasis of network activity. Four decades
      of lesion studies have brought up a wealth of data on the mutual interdependence
      of neuronal activity, neurotransmitter release and neuronal morphogenesis and
      network formation. Here, we review these former studies on structural plasticity
      in the context of recent experimental studies. We compare spontaneous and
      experience-dependent structural plasticity with lesion-induced (reactive)
      structural plasticity that occurs during development and in the adult brain.
      Understanding the principles of neural network reorganization on a structural
      level is relevant for a deeper understanding of long-term memory formation as
      well as for the treatment of neurological diseases such as stroke.

PMID- 19162070
TI  - Forebrain pain mechanisms.
AB  - Emotional-affective and cognitive dimensions of pain are less well understood
      than nociceptive and nocifensive components, but the forebrain is believed to
      play an important role. Recent evidence suggests that subcortical and cortical
      brain areas outside the traditional pain processing network contribute critically
      to emotional-affective responses and cognitive deficits related to pain. These
      brain areas include different nuclei of the amygdala and certain prefrontal
      cortical areas. Their roles in various aspects of pain will be discussed.
      Biomarkers of cortical dysfunction are being identified that may evolve into
      therapeutic targets to modulate pain experience and improve pain-related
      cognitive impairment. Supporting data from preclinical studies in neuropathic
      pain models will be presented. Neuroimaging analysis provides evidence for
      plastic changes in the pain processing brain network. Results of clinical studies
      in neuropathic pain patients suggest that neuroimaging may help determine
      mechanisms of altered brain functions in pain as well as monitor the effects of
      pharmacologic interventions to optimize treatment in individual patients. Recent
      progress in the analysis of higher brain functions emphasizes the concept of pain
      as a multidimensional experience and the need for integrative approaches to
      determine the full spectrum of harmful or protective neurobiological changes in
      pain.

PMID- 19162071
TI  - Rapid pain modulation with nuclear receptor ligands.
AB  - We discuss and present new data regarding the physiological and molecular
      mechanisms of nuclear receptor activation in pain control, with a particular
      emphasis on non-genomic effects of ligands at peroxisome proliferator-activated
      receptor (PPAR), GPR30, and classical estrogen receptors. PPARalpha agonists
      rapidly reduce both acute and chronic pain in a number of pain assays. These
      effects precede transcriptional anti-inflammatory actions, and are mediated in
      part by IK(ca) and BK(ca) channels on DRG neurons. In contrast to the peripheral
      site of action of PPARalpha ligands, the dorsal horn supports the expression of
      PPARgamma. Intrathecal administration of PPARgamma ligands rapidly (< or =5 min)
      attenuated mechanical and thermal hypersensitivity associated with nerve injury
      in a dose-dependent manner that could be blocked with PPARgamma antagonists. By
      contrast, a PPARgamma antagonist itself rapidly increased the mechanical
      allodynia associated with nerve injury. These data suggest that ligand-dependent,
      non-genomic activation of spinal PPARgamma decreases behavioral signs of
      inflammatory and neuropathic pain. We also report that the GPR30 is expressed on
      cultured sensory neurons, that activation of the receptor elicits signaling to
      increase calcium accumulation. This signaling may contribute to increased
      neuronal sensitivity as treatment with the GPR30 agonist induces hyperalgesia.
      Finally, application of the membrane-impermeable 17beta-E(2)-BSA rapidly (within
      15 min) enhanced BK-stimulated inositol phosphate (IP) accumulation and PGE(2)
      mediated cAMP accumulation in trigeminal ganglion cultures. We conclude that
      nuclear receptor ligands may operate through rapid, non-genomic mechanisms to
      modulate inflammatory and neuropathic pain.

PMID- 19162073
TI  - Evaluating statistical methods used to estimate the number of postsynaptic
      receptors.
AB  - Calcium levels in spines play a significant role in determining the sign and
      magnitude of synaptic plasticity. The magnitude of calcium influx into spines is
      highly dependent on influx through N-methyl D-aspartate (NMDA) receptors, and
      therefore depends on the number of postsynaptic NMDA receptors in each spine. We
      have calculated previously how the number of postsynaptic NMDA receptors
      determines the mean and variance of calcium transients in the postsynaptic
      density, and how this alters the shape of plasticity curves. However, the number
      of postsynaptic NMDA receptors in the postsynaptic density is not well known.
      Anatomical methods for estimating the number of NMDA receptors produce estimates
      that are very different than those produced by physiological techniques. The
      physiological techniques are based on the statistics of synaptic transmission and
      it is difficult to experimentally estimate their precision. In this paper we use
      stochastic simulations in order to test the validity of a physiological
      estimation technique based on failure analysis. We find that the method is likely
      to underestimate the number of postsynaptic NMDA receptors, explain the source of
      the error, and re-derive a more precise estimation technique. We also show that
      the original failure analysis as well as our improved formulas are not robust to
      small estimation errors in key parameters.

PMID- 19162074
TI  - Semi-automated method for delineation of landmarks on models of the cerebral
      cortex.
AB  - Sulcal and gyral landmarks on the human cerebral cortex are required for various
      studies of the human brain. Whether used directly to examine sulcal geometry, or
      indirectly to drive cortical surface registration methods, the accuracy of these
      landmarks is essential. While several methods have been developed to
      automatically identify sulci and gyri, their accuracy may be insufficient for
      certain neuroanatomical studies. We describe a semi-automated procedure that
      delineates a sulcus or gyrus given a limited number of user-selected points. The
      method uses a graph theory approach to identify the lowest-cost path between the
      points, where the cost is a combination of local curvature features and the
      distance between vertices on the surface representation. We implemented the
      algorithm in an interface that guides the user through a cortical surface
      delineation protocol, and we incorporated this tool into our BrainSuite software.
      We performed a study to compare the results produced using our method with
      results produced using Display, a popular tool that has been used extensively for
      manual delineation of sulcal landmarks. Six raters were trained on the
      delineation protocol. They performed delineations on 12 brains using both
      software packages. We performed a statistical analysis of 3 aspects of the
      delineation task: time required to delineate the surface, registration accuracy
      achieved compared to an expert-delineated gold-standard, and variation among
      raters. Our new method was shown to be faster to use, to provide reduced inter
      rater variability, and to provide results that were at least as accurate as those
      produced using Display.

PMID- 19162075
TI  - Persistent replication of the GBV-C subgenomic replicons in Huh7 cells.
AB  - Studies of GB virus type C (GBV-C) replication in vitro have been limited because
      of poor growth of GBV-C in cell culture. In order to address the infection of GBV
      C, two GBV-C subgenomic replicons (GBCrepEGFP and GBCrepTNF) were developed from
      a GBV-C full-length genomic cDNA. The viral replication, protein expression and
      the production of virus-like particles were evaluated in human hepatoma cell line
      Huh7. The results showed that the established GBCrepEGFP and GBCrepTNF replicons
      could be replicated autonomously and expressed in cell culture for at least 2
      months and 1 month respectively. The replicon RNA could assemble RNA-containing
      structures in the HuhEH cells expressing GBV-C structural proteins. It suggests
      that a cell line supporting the replication of GBV-C was established. This
      replicon system might be used to understand better the biology of GBV-C.

PMID- 19162076
TI  - Development of a gene capture method to rescue a large deletion mutant of human
      cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) is an opportunistic human pathogen that causes
      serious clinical illness in immunocompromised individuals. A major breakthrough
      in the progression of HCMV genetics studies is the development of bacterial
      artificial chromosome (BAC) clones of the viral genome. Recently, a luciferase
      reporter gene was inserted in the BAC clone (BAC(luc)) which facilitates
      monitoring of the virus growth both in vitro and in vivo. The virus made from the
      BAC(luc) grew with the similar kinetics as the wild-type strain indicating that
      the luciferase gene insertion does not interfere with the virus growth. Although
      the construction of the BAC clone has eased genetic studies of herpesviruses
      tremendously, there are still difficulties in cloning large DNA fragments of the
      virus to rescue mutations with large deletions. This paper describes a novel
      method termed "gene capture", which allows easier cloning of large pieces of DNA.
      As an application of this method, a 15-kb fragment that was deleted from the HCMV
      genome was rescued back into the viral genome. A mutant HCMV clone with the 15-kb
      region deletion was generated first using the lambda prophage recombination
      system in E. coli. Utilizing the new rescue method, the deleted fragment was then
      rescued in two steps: the 15-kb region was captured into a vector by homologous
      recombination; and the captured DNA fragment from the vector was inserted back
      into its native site in the mutant viral BAC by second homologous recombination.
      This method will be useful particularly for cloning large DNA fragments from any
      genome without introducing undesired mutations by traditional PCR-based
      approaches.

PMID- 19162077
TI  - Cognitive map in patients with mild Alzheimer's disease: a computer-generated
      arena study.
AB  - OBJECTIVE: In addition to memory impairment, a tendency to get lost is among the
      initial symptoms in patients with Alzheimer disease (AD). At least two kinds of
      wayfinding strategies, egocentric and allocentric, have been proposed. It is
      believed that people may form a cognitive map after repeated movement in a
      specific environment, and are able to use it as an aid to navigation. In the
      present study, we investigated the cognitive maps in early AD patients and their
      application in a computer-generated arena (CGA). METHODS: We invited very mild AD
      (CDR 0.5) patients and normal controls (NCs) to participate in the current study.
      Hand-drawing tests were used to assess their supposedly previously formed
      cognitive maps of familiar environments, and CGA was used to measure their new
      environment learning as well as the application of the old map. RESULTS: Nineteen
      patients (8 females, mean age 67.6 years old, education 9.7 years, and MMSE 24)
      and 18 NCs (10 females, mean age 66.4 years old, education 8.8 years, and MMSE
      27) completed the study. In the hand-drawing map part, both groups did equally
      well. In the new environment learning, NCs did better than the AD group on the
      third of six trials. As for the old environment navigation experiment, the AD
      group spent more time than the NCs in finding the target, but showed no
      difference to NC regarding the path traveled in the target quadrant. CONCLUSION:
      Early AD patients maintain their ability to use a cognitive map and keep pretty
      good allocentric representation of their familiar environments as well as NC do,
      but probably both groups do not routinely use their cognitive map to navigate in
      everyday life properly.

PMID- 19162078
TI  - Effects of neuronal Kv7 potassium channel activators on hyperactivity in a rodent
      model of mania.
AB  - In an effort to investigate the potential antimanic-like activity of K(v)7
      channel openers, we decided to test: (1) the subtype non-selective K(v)7 opener
      retigabine, (2) the K(v)7.4-K(v)7.5 (and K(v)7.5/3 heteromers) preferring channel
      opener BMS-204352 (Maxipost), and (3) the novel K(v)7.2/3 preferring channel
      opener ICA-27243, in the amphetamine (AMPH)+chlordiazepoxide (CDP)-induced
      hyperactivity paradigm in mice, a test often used to assess potential antimanic
      like activity of novel compounds. Lithium and lamotrigine were included as
      positive controls. Pretreatment with lithium attenuated AMPH/CDP-induced
      hyperactivity, without affecting the activity of AMPH- or CDP-alone, and thus
      confirmed some predictive validity for the test paradigm. Pretreatment with
      lamotrigine significantly attenuated AMPH/CDP-induced effects, but also reduced
      motility when tested in the presence of CDP-alone. Pretreatment with retigabine
      or ICA-27243 attenuated AMPH/CDP-induced hyperactivity without affecting basal
      locomotor activity. In contrast, pretreatment with BMS-204352 failed to decrease
      AMPH/CDP-induced hyperactivity at lower doses (3 and 10 mg/kg). At higher doses
      BMS-204352 attenuated hyperactivity induced by the AMPH/CDP mix, but only at
      doses decreasing basal locomotor activity (30 and 60 mg/kg). None of the K(v)7
      openers tested significantly affected AMPH-induced hyperactivity. In contrast,
      retigabine and ICA-27243 were shown to induce significant reductions in motility
      when administered in combination with CDP-alone. In conclusion, the results with
      lithium confirm some predictive validity for the test paradigm. However, our data
      highlight an important confounder for interpreting a role for K(v)7 channels in
      the alleviation of manic-like symptoms when employing the AMPH/CDP hyperactivity
      model in mice. It is imperative that relevant control studies (AMPH- and CDP
      alone) be incorporated and reported routinely to enable thorough interpretation
      of data generated by means of this behavioural test.

PMID- 19162079
TI  - Stimulus-induced gamma activity in the electrocorticogram of freely moving rats:
      the neuronal signature of novelty detection.
AB  - To investigate the cortical activity pattern associated with the exploration and
      identification of a novel object we recorded the intracranial electrocorticogram
      (ECoG) in the barrel cortex of freely moving adult rats using wireless
      technology. We report here that the exploration and detection of a novel object
      correlate with a transient increase of synchronized oscillatory activity in the
      40-47 Hz frequency band. This specific cortical activity pattern occurs 200-300
      ms after the first sensory contact with the novel stimulus and decreases in power
      in the subsequent recording sessions with the same object. During the first
      explorative session the increase in 40-47 Hz is associated with a simultaneous
      decrease in the 30-37 Hz band, which increased to a stable level already after
      one session. Our results indicate that synchronized gamma activities in primary
      sensory cortex may represent the neuronal signature for the detection of a novel
      object.

PMID- 19162080
TI  - Aging and time-of-day effects on anxiety in female Octodon degus.
AB  - Animal models of anxiety have usually employed nocturnal species (e.g. rats and
      mice), and the tests used have been almost exclusively performed during the
      diurnal phase (lights on). Here, for the first time, we tested anxiety in a
      diurnal rodent, Octodon degus, according to its age (23 versus 40 months of age)
      and the time of the day. We employed three anxiety tests: object recognition,
      open field and light-dark tests, which were applied in the morning, at mid-day
      and in the late afternoon, respectively. Adult animals spent more time exploring
      a new object than aged animals. Nevertheless, there were no differences in the
      frequency of object exploration or in the latency to the first object approach
      between the groups. In the open field test, adult animals spent more time
      exploring (ambulation and rearing) than aged ones. Although both groups exhibited
      similar frequencies in transition from the dark to the light box in the light
      dark test, adult animals spent significantly more time in the light, and
      expressed less anxiety when making the decision to cross over from the dark into
      the light area. In conclusion, there were no differences in anxiety between adult
      and aged animals in the morning session, although adult animals were more
      attentive when exploring a new object. However, in the mid-day and afternoon
      testing sessions, aged animals were more anxious than adults.

PMID- 19162081
TI  - Differential place and response learning in horses displaying an oral stereotypy.
AB  - Significant similarities exist between the neural and behavioural features of
      environmentally and drug-induced stereotypy. For example, exposure to dopamine
      agonists, such as amphetamine, induces stereotypy and causes alterations in
      midbrain neurophysiology similar to those observed following chronic stress. An
      additional behavioural feature of these neural changes in the drug-induced
      phenotype is an enhanced rate of switching from response-outcome (R-O) to
      stimulus-response (S-R) learning. The aim of the current experiment was to
      examine R-O and S-R learning in horses displaying environmentally induced oral
      stereotypies. This was achieved by employing variations of the place/response
      paradigm. In Experiment 1, we found that crib-biting horses displayed 'response'
      learning after 20 learning trials, whereas non-crib-biting controls tended to
      display 'place' learning throughout the experiment. In Experiment 2, we used a
      modified version of the procedure, in which the subjects were introduced to the
      maze from different start points and forced always to turn the same way. We found
      that the crib-biters acquired the task at a faster rate suggesting again that
      this group was displaying 'response' learning. Finally, in Experiment 3, we
      carried out an arena test to ensure that crib-biters were capable of 'place'
      learning. These results are the first to show that horses displaying an oral
      stereotypy, a behavioural phenotype previously associated with stress-induced
      perturbations of the basal ganglia, preferentially use 'response' learning. The
      findings are discussed in relation to the search for an aetiological model of
      stereotypy.

PMID- 19162082
TI  - Modulation of anxiety by acute blockade and genetic deletion of the CB(1)
      cannabinoid receptor in mice together with biogenic amine changes in the
      forebrain.
AB  - The CB(1) cannabinoid receptor has been implicated in the control of fear and
      anxiety. We investigated the effects of genetic and pharmacological blockade of
      the CB(1) cannabinoid receptor on the behaviour of CD1 mice using three different
      ethological models of fear and anxiety (elevated T-maze and plus-maze and open
      field test of emotionality). Furthermore, we measured tissue levels of
      noradrenalin (NA), dopamine (DA), serotonin (5-HT) and their metabolites in
      several forebrain regions, i.e. prefrontal cortex, hippocampus, septum, dorsal
      and ventral striatum to examine the relationship between CB(1) receptor
      manipulation and monoaminergic neurotransmission. The major findings can be
      summarized as follows: the CB(1) receptor antagonist SR141617A (rimonabant)
      modulated anxiety in a dose-dependent manner. At a dose of 3 mg/kg i.p., the
      compound consistently increased anxiety parameters in all of the three different
      anxiety tests applied, while a lower dosage of 1mg/kg had no such effect. The
      neurochemical evaluation of the mice administered 3mg/kg SR141617A revealed
      increases in the concentrations of DOPAC and 5-HIAA in the dorsal striatum,
      elevated DA levels in the hippocampus and reduced dopamine turnover in the
      septum. Furthermore, these animals had a higher HVA/DA turnover in the frontal
      cortex. CB(1) receptor knockout mice as well as mice treated with the selective
      CB(1) receptor antagonist AM251 (3 mg/kg; i.p.) did not display any significant
      alterations in anxiety-related behaviour as measured with the elevated plus-maze
      and open field test of emotionality, respectively. Our findings support the
      general idea of a SR141617A-sensitive receptive site that is different from the
      'classical' CB(1) receptor and that has a pivotal role in the regulation of
      different psychological functions. However, with regard to its functional
      significance in terms of anxiety our findings suggest that under physiological
      conditions this receptive site seems to be involved in the control of anxiolysis
      rather than anxiogenesis as suggested previously.

PMID- 19162083
TI  - Evidence for the involvement of the opioid system in the antidepressant-like
      effect of folic acid in the mouse forced swimming test.
AB  - The opioid system has been implicated in major depression and in the mechanism of
      action of antidepressants. This study investigated the involvement of the opioid
      system in the antidepressant-like effect of the water-soluble B-vitamin folic
      acid in the forced swimming test (FST). The effect of folic acid (10 nmol/site,
      i.c.v.) was prevented by the pretreatment of mice with naloxone (1 mg/kg, i.p., a
      nonselective opioid receptor antagonist), naltrindole (3 mg/kg, i.p., a selective
      delta-opioid receptor antagonist), naloxonazine (10 mg/kg, i.p., a selective
      mu(1)-opioid receptor antagonist, 24 h before), but not with naloxone methiodide
      (1 mg/kg, s.c., a peripherally acting opioid receptor antagonist). In addition, a
      sub-effective dose of folic acid (1 nmol/site, i.c.v.) produced a synergistic
      antidepressant-like effect in the FST with a sub-effective dose of morphine (1
      mg/kg, s.c.). A further approach was designed to investigate the possible
      relationship between the opioid system and NMDA receptors in the mechanism of
      action of folic acid in the FST. Pretreatment of the animals with naloxone (1
      mg/kg, i.p.) prevented the synergistic antidepressant-like effect of folic acid
      (1 nmol/site, i.c.v.) and MK-801 (0.001 mg/kg, i.p., a non-competitive NMDA
      receptor antagonist). Together the results firstly indicate that the anti
      immobility effect of folic acid in the FST is mediated by an interaction with the
      opioid system (mu(1) and delta), likely dependent on the inhibition of NMDA
      receptors elicited by folic acid.

PMID- 19162085
TI  - Temporal processing of olfactory stimuli during retronasal perception.
AB  - Odorants can be perceived via the nose during an inhalation or sniff (orthonasal
      perception) and via the mouth, nasopharynx and nasal cavity during mastication or
      drinking (retronasal perception). Previous data suggest that orthonasal
      perception provides a more efficient route with greater difficulty being reported
      when detecting [Halpern BP. Retronasal and orthonasal smelling. Chemosense
      2004;6:1-7; Voirol E, Daget N. Comparative study of nasal and retronasal
      olfactory perception. Lebensmittel-Wissenschaft Technol 1986;19:316-9] and
      identifying [Heilmann S, Hummel T. A new method for comparing orthonasal and
      retronasal olfaction. Behav Neurosci 2004;118:412-9; Sun BC, Halpern BP.
      Identification of air-phase retronasal and orthonasal odorant pairs. Chem Senses
      2005;30:1-14] single odorants retronasally. Whether the poorer sensitivity
      obtained via the retronasal route is largely due to the greater adsorption of
      odorants by the nasopharyngeal mucus compared to the nasal mucus thereby reducing
      their peak concentration and/or slowing their passage, has not been resolved.
      Importantly, the question of whether solubility of odorants in mucus or water
      predicts the outcomes for perception of stimuli presented via the retronasal
      route has not been resolved. Accordingly, the present study investigates this
      question by determining whether the solubility of an odorant in mucus predicts
      which component of a binary odour mixture is perceived first during retronasal
      perception. The results indicate that solubility in mucus rather than solubility
      in water is a better predictor of which odour will be perceived first and
      identified more readily during the retronasal perception of a binary mixture. In
      addition, lower intensity levels of single odorants occurred via the retronasal
      route suggesting that adsorption was greater via this route. Whether this was due
      to nasopharyngeal mucus having a greater adsorptive area or different composition
      compared to the orthonasal pathway is not known.

PMID- 19162086
TI  - The occurrence of a deficit in contextual fear extinction in adult amyloid-over
      expressing TASTPM mice is independent of the strength of conditioning but can be
      prevented by mild novel cage stress.
AB  - In the amyloid over-expressing TASTPM mouse model of Alzheimer's disease,
      impaired contextual fear memory occurs early, and is preceded, at 4 months of
      age, by a deficit in extinction of contextual fear that is resistant to
      improvement by repeated mild novel cage stress. The first aim of this study was
      thus to establish whether the extinction deficit could be prevented if the novel
      cage procedure was applied prior to its onset. The second aim was to establish
      whether the occurrence of the extinction deficit was dependent on the robustness
      of the conditioning protocol. We first compared 3-month-old wild-type and TASTPM
      mice for acquisition, retention and extinction of contextual fear and then,
      looked at the impact of 5 weeks of novel cage stress (4 x 1 h/week) applied from
      3 months onwards, on age-related changes in these behaviours evaluated at 4.5
      months of age. In another experiment, we compared 4-month-old TASTPM and wild
      type mice for the impact of a 2 and 5-pairing conditioning procedure on the three
      phases of contextual fear conditioning. In 4.5-month-old TASTPM mice, the deficit
      in extinction was alleviated by repeated novel cage stress, applied from prior to
      its onset at 3 months. At 4 months of age, the occurrence of an extinction
      deficit was independent of the strength of the conditioning procedure, in TASTPM
      mice, which even showed an increase in aversive memory under the 2-pairing
      condition. The robust early impairment in the extinction of contextual fear seen
      in adult TASTPM mice suggests that a deficit in cognitive flexibility is the
      first sign of behavioural pathology in this model of Alzheimer's disease.

PMID- 19162084
TI  - A neurocomputational model of tonic and phasic dopamine in action selection: a
      comparison with cognitive deficits in Parkinson's disease.
AB  - The striatal dopamine signal has multiple facets; tonic level, phasic rise and
      fall, and variation of the phasic rise/fall depending on the expectation of
      reward/punishment. We have developed a network model of the striatal direct
      pathway using an ionic current level model of the medium spiny neuron that
      incorporates currents sensitive to changes in the tonic level of dopamine. The
      model neurons in the network learn action selection based on a novel set of
      mathematical rules that incorporate the phasic change in the dopamine signal.
      This network model is capable of learning to perform a sequence learning task
      that in humans is thought to be dependent on the basal ganglia. When both tonic
      and phasic levels of dopamine are decreased, as would be expected in unmedicated
      Parkinson's disease (PD), the model reproduces the deficits seen in a human PD
      group off medication. When the tonic level is increased to normal, but with
      reduced phasic increases and decreases in response to reward and punishment,
      respectively, as would be expected in PD medicated with L-Dopa, the model again
      reproduces the human data. These findings support the view that the cognitive
      dysfunctions seen in Parkinson's disease are not solely either due to the
      decreased tonic level of dopamine or to the decreased responsiveness of the
      phasic dopamine signal to reward and punishment, but to a combination of the two
      factors that varies dependent on disease stage and medication status.

PMID- 19162087
TI  - Intermediate- and long-term recognition memory deficits in Tg2576 mice are
      reversed with acute calcineurin inhibition.
AB  - The Tg2576 transgenic mouse is an extensively characterized animal model for
      Alzheimer's disease (AD). Similar to AD, these mice suffer from progressive
      decline in several forms of declarative memory including contextual fear
      conditioning and novel object recognition (NOR). Recent work on this and other AD
      animal models suggests that initial cognitive deficits are due to synaptic
      dysfunction that, with the correct intervention, are fully treatable. We recently
      reported that acute calcineurin (CaN) inhibition with FK506 ameliorates one form
      of declarative memory (contextual fear conditioning) impairment in 5 months old
      Tg2576. This study tested whether acute CaN inhibition rescues deficits in an
      additional form of declarative memory, spontaneous object recognition, by
      employing the NOR paradigm. Furthermore, we determined whether FK506 rescue of
      NOR deficits depends on the retention interval employed and therefore is
      restricted to short-term, intermediate-term, or long-term memory (STM, ITM or
      LTM, respectively). In object recognition, Tg2576 are unimpaired when NOR is
      tested as a STM task and CaN inhibition with FK506 does not influence NOR STM
      performance in Tg2576 or WT mice. Tg2576 were impaired in NOR compared to WT mice
      when a 4 or 24h retention interval was employed to model ITM and LTM,
      respectively. Acute CaN inhibition prior to and during the training session
      reversed these deficits in Tg2576 mice with no effect on WT performance. Our
      findings demonstrate that aberrant CaN activity mediates object recognition
      deficits in 5 months old Tg2576 when NOR is employed as a test for ITM and LTM.
      In human AD, CaN inhibition may lead the way for therapeutics to improve
      declarative memory performance as demonstrated in a mouse model for AD.

PMID- 19162088
TI  - Sex-dependent effect of cyclooxygenase-2 inhibition on mouse spatial memory.
AB  - Cyclooxygenase (COX)-2 is constitutively expressed in neurons of the hippocampus
      and neocortex. Therefore, non-steroidal anti-inflammatory drugs (NSAIDs)
      targeting inflammation-induced COX-2 in the periphery and the central nervous
      system may also affect cognitive function mediated by basal COX-2 activity. We
      report that systemic administration of the selective COX-2 inhibitor NS-398 6h
      prior to behavioral assessment does not influence spatial acquisition or
      retention in male C57BL/6J mice. However, we observed impaired spatial retention
      in female mice treated with NS-398, suggesting a sex-dependent role of COX-2 in
      spatial memory of mice.

PMID- 19162089
TI  - Patterns of early embryonic light exposure determine behavioural asymmetries in
      zebrafish: a habenular hypothesis.
AB  - Releasers of innate responses are more effective in many vertebrates when seen by
      the left eye. In zebrafish Brachydanio rerio, this asymmetry is linked with
      neuroanatomical asymmetry of the habenular complex (enlarged left lateral and
      right medial habenular nuclei): if habenular asymmetry is reversed, reader
      response to releasers shifts to the right eye. Light exposure (schedule:
      14/10h,L/D) during the first few days of development post fertilisation (pf)
      controls the patterning of this asymmetry. We show here, using response to a
      model predator on day 7 pf, that absence of light on day 1 pf alone causes high
      responsiveness to shift from left to right eye and to intensify. Absence on day 2
      pf or day 3 pf produces lesser shifts, whereas absence for all 3 days reduces
      responsiveness without any shift. Action on day 1 pf is likely to be due to
      modulation of gene expression. A known disturbance of gene (nrp1a) expression
      causes rerouting of the outflow of the left lateral habenula to the way station
      of the right medial habenula, providing a possible explanation of shifts.
      Variation in exposure of eggs to light is likely to produce inter-individual
      variation in the field.

PMID- 19162090
TI  - The regulation of tenascin expression by tissue microenvironments.
AB  - Tenascins are a family of four extracellular matrix proteins: tenascin-C, X, R
      and W. The four members of the family have strikingly diverse patterns of
      expression during development and in the adult organism indicating independent
      mechanisms of regulation. In this review we illustrate that there are two types
      of tenascins, those that are significantly regulated by the tissue
      microenvironment (tenascin-C and tenascin-W), and those that have stabile,
      restricted expression patterns (tenascin-R and tenascin-X). We summarize what is
      known about the regulation of tenascin expression by transforming growth factor
      betas, fibroblast growth factors, platelet derived growth factors, as well as pro
      and anti-inflammatory cytokines or hormones that either induce or inhibit
      expression of tenascins.

PMID- 19162091
TI  - A high throughput Nile red method for quantitative measurement of neutral lipids
      in microalgae.
AB  - Isolation of high neutral lipid-containing microalgae is key to the commercial
      success of microalgae-based biofuel production. The Nile red fluorescence method
      has been successfully applied to the determination of lipids in certain
      microalgae, but has been unsuccessful in many others, particularly those with
      thick, rigid cell walls that prevent the penetration of the fluorescence dye. The
      conventional "one sample at a time" method was also time-consuming. In this
      study, the solvent dimethyl sulfoxide (DMSO) was introduced to microalgal samples
      as the stain carrier at an elevated temperature. The cellular neutral lipids were
      determined and quantified using a 96-well plate on a fluorescence
      spectrophotometer with an excitation wavelength of 530 nm and an emission
      wavelength of 575 nm. An optimized procedure yielded a high correlation
      coefficient (R(2)=0.998) with the lipid standard triolein and repeated
      measurements of replicates. Application of the improved method to several green
      algal strains gave very reproducible results with relative standard errors of
      8.5%, 3.9% and 8.6%, 4.5% for repeatability and reproducibility at two
      concentration levels (2.0 microg/mL and 20 microg/mL), respectively. Moreover,
      the detection and quantification limits of the improved Nile red staining method
      were 0.8 microg/mL and 2.0 microg/mL for the neutral lipid standard triolein,
      respectively. The modified method and a conventional gravimetric determination
      method provided similar results on replicate samples. The 96-well plate-based
      Nile red method can be used as a high throughput technique for rapid screening of
      a broader spectrum of naturally-occurring and genetically-modified algal strains
      and mutants for high neutral lipid/oil production.

PMID- 19162092
TI  - Evaluation of serological tests for the diagnosis of rickettsiosis in Denmark.
AB  - Two commercially available immunofluorescence assays (IFA) were compared using
      historical sera evaluated for rickettsial antibodies by the Weil-Felix test. An
      IFA test produced by Focus Diagnostics prepared with Rickettsia rickettsii and R.
      typhi antigens was compared with a custom made kit from Fuller Laboratories with
      R. rickettsii, R. typhi, R. conorii and R. helvetica as antigens. The serum panel
      used for the comparison included Weil-Felix-positive and -negative samples. Cross
      reactions were analyzed using serum samples from patients with clinical symptoms
      similar to those of rickettsiosis. When analyzing the data using the
      manufacturers' cut-off values, 41% of samples from presumably healthy blood
      donors were found positive for spotted fever group Rickettsia antibodies. This
      does not correlate to the general picture of rickettsiosis in Denmark.
      Furthermore, sera with Coxiella burnetii antibodies were found to be cross
      reacting in both tests. When applying cut-off values calculated on the 95%
      percentile on data from blood donor serum samples, there was no significant
      difference between the two kits. Moreover, when using the newly established cut
      off, cross-reactions were eliminated.

PMID- 19162093
TI  - Multiplex quantification of 16S rDNA of predominant bacteria group within human
      fecal samples by polymerase chain reaction--ligase detection reaction (PCR-LDR).
AB  - A new method, based on ligase detection reaction (LDR), was developed for
      quantitative detection of multiplex PCR amplicons of 16S rRNA genes present in
      complex mixtures (specifically feces). LDR has been widely used in single
      nucleotide polymorphism (SNP) assay but never applied for quantification of
      multiplex PCR products. This method employs one pair of DNA probes, one of which
      is labeled with fluorescence for signal capture, complementary to the target
      sequence. For multiple target sequence analysis, probes were modified with
      different lengths of polyT at the 5' end and 3' end. Using a DNA sequencer, these
      ligated probes were separated and identified by size and dye color. Then,
      relative abundance of target DNA were normalized and quantified based on the
      fluorescence intensities and exterior size standards. 16S rRNA gene of three
      preponderant bacteria groups in human feces: Clostridium coccoides, Bacteroides
      and related genera, and Clostridium leptum group, were amplified and cloned into
      plasmid DNA so as to make standard curves. After PCR-LDR analysis, a strong
      linear relationship was found between the florescence intensity and the diluted
      plasmid DNA concentrations. Furthermore, based on this method, 100 human fecal
      samples were quantified for the relative abundance of the three bacterial groups.
      Relative abundance of C. coccoides was significantly higher in elderly people in
      comparison with young adults, without gender differences. Relative abundance of
      Bacteroides and related genera and C. leptum group were significantly higher in
      young and middle aged than in the elderly. Regarding the whole set of sample, C.
      coccoides showed the highest relative abundance, followed by decreasing groups
      Bacteroides and related genera, and C. leptum. These results imply that PCR-LDR
      can be feasible and flexible applied to large scale epidemiological studies.

PMID- 19162094
TI  - An optimised protocol to prepare Phaeocystis globosa morphotypes for scanning
      electron microscopy observation.
AB  - A preparation protocol for scanning electron microscopy (SEM) was adapted and
      tested to the observation of Phaeocystis globosa morphotypes. For extra colonial
      cells, critical point drying (CPD) gave satisfactory results while for intra
      colonial cells, preservation with Lugol's iodine and/or glutaraldehyde followed
      by air-drying appeared as the most suitable method.

PMID- 19162095
TI  - Movement related cortical potentials in a face naming task: influence of the tip
      of-the-tongue state.
AB  - The aim of the present study was evaluate the movement-related cortical
      potentials (MRCPs) associated with manual and speech movements during a face
      naming task carried out by the same participants as in a previous study, in order
      to: 1) determine whether the slowing down of the reaction time observed in the
      tip-of-the-tongue (TOT) state was caused by motor processes; 2) compare the MRCPs
      among the three response categories (tip-of-the-tongue, successful retrieval and
      not knowing the name); and 3) determine whether the MRCPs modulated the
      differences in amplitude of the late negative wave among response categories. The
      first component of readiness potential, the negative slope, the motor potential
      and the reafferent potential associated with the manual response, and two
      components associated with the verbal responses-the speech-related motor
      potential and the speech-related reafferent potential-were identified. The
      slowing down of reaction time observed in the TOT category may be due to a
      temporal interruption in the motor programming of the responses due to the TOT
      state. The longer latency in speech-related components in the KNOW with respect
      to the TOT category can be attributed to the greater cognitive demands involved
      in the retrieval of proper names in the former category. The brain activity
      associated with the preparation and execution of the responses had a differential
      modulatory effect on the amplitude of the LNW component, which may partially
      explain the differences between the categories observed in the previous study by
      Diaz et al. [Diaz, F., Lindin, M., Galdo-Alvarez, S., Facal, D., Juncos-Rabadan,
      O., 2007. An event-related potentials study of face identification and naming:
      the tip-of-the-tongue state. Psychophysiology 44, 50-68].

PMID- 19162096
TI  - Production of monoclonal antibodies by glycoengineered Pichia pastoris.
AB  - The growing antibody market and the pressure to improve productivity as well as
      reduce cost of production have fueled the development of alternative expression
      systems. The therapeutic function of many antibodies is influenced by N-linked
      glycosylation, which is affected by a combination of the expression host and
      culture conditions. This paper reports the generation of a glycoengineered Pichia
      pastoris strain capable of producing more than 1 g l(-1) of a functional
      monoclonal antibody in a robust, scalable and portable cultivation process with
      uniform N-linked glycans of the type Man(5)GlcNAc(2). N-linked glycan uniformity
      and volumetric productivity have been maintained across a range of cultivation
      process conditions including pH (5.5-7.5), temperature (16-24 degrees C),
      dissolved oxygen concentration (0.85-3.40 mg l(-1)) and specific methanol feed
      rate (9-19 mg g(-1) h(-1)) as well as across different cultivation scales (0.5,
      3.0, 15 and 40 l). Compared to a marketed CHO-produced therapeutic antibody, the
      glycoengineered yeast-produced antibody has similar motilities on SDS-PAGE,
      comparable size exclusion chromatograms (SEC) and antigen binding affinities.
      This paper provides proof of concept that glycoengineered yeast can be used to
      produce functional full-length monoclonal antibodies at commercially viable
      productivities.

PMID- 19162097
TI  - Pathway identification combining metabolic flux and functional genomics analyses:
      acetate and propionate activation by Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum can utilize acetic acid and propionic acid for growth
      and amino acid production. Growth on acetate as sole carbon source requires
      acetate activation by acetate kinase (AK) and phosphotransacetylase (PTA),
      encoded in the pta-ack operon. Genetic and enzymatic studies showed that these
      enzymes also catalyze propionate activation and were required for growth on
      propionate as sole carbon source. However, when glucose was present as a co
      substrate strain lacking the AK-PTA pathway was still able to utilize acetate or
      propionate for growth indicating that an alternative activation pathway exists.
      As shown by (13)C-labelling experiments, the carbon skeleton of acetate is
      conserved during activation to acetyl-CoA in this pathway. Metabolic flux
      analysis during growth on an acetate-glucose mixture revealed that in the absence
      of the AK-PTA pathway carbon fluxes in glycolysis, the tricarboxylic acid (TCA)
      cycle and anaplerosis via PEP carboxylase and/or pyruvate carboxylase were
      increased, while the glyoxylate cycle flux was decreased. DNA microarray
      experiments identified cg2840 as a constitutively and highly expressed gene
      putatively encoding a CoA transferase. Purified His-tagged Cg2840 protein was
      active as CoA transferase interconverting acetyl-, propionyl- and succinyl
      moieties as CoA acceptors and donors. Strains lacking both the CoA transferase
      and the AK-PTA pathway could neither activate acetate nor propionate in the
      presence or absence of glucose. Thus, when these short-chain fatty acids are co
      metabolized with other carbon sources, CoA transferase and the AK-PTA pathway
      constitute a redundant system for activation of acetate and propionate.

PMID- 19162098
TI  - Molecular characterization of a canine respiratory coronavirus strain detected in
      Italy.
AB  - Coronaviruses (CoVs) are positive-stranded, non-segmented RNA viruses generally
      responsible for the emergence of respiratory and enteric disease in humans,
      companion animals and livestock. Their aptitude to evolve by genetic
      recombination and/or point mutation is recognized, thus giving rise to new viral
      genotypes and mutants with different tissues or host tropism. In particular, a
      probable origin from the strictly related bovine coronavirus (BCoV) or,
      alternatively, from a common ancestor has been suggested for some group 2a CoVs,
      including canine respiratory coronavirus (CRCoV). In this study, we report the
      sequence analysis of the viral RNA 3'-end of an Italian CRCoV, strain 240/05,
      together with the sequence comparison with extant bovine-like viruses including
      the sole CRCoV strain 4182 previously described. Interestingly, although the
      structural proteins show the same features of CRCoV 4182, the genomic region
      between the spike and the envelope protein genes of CRCoV 240/05 encodes for
      three distinct products, including the equivalent bovine 4.9 kDa non-structural
      protein and a truncated form of the 4.8 kDa protein, whereas CRCoV 4182 has a
      unique 8.8 kDa protein.

PMID- 19162099
TI  - Sequence analysis of divergent canine coronavirus strains present in a UK dog
      population.
AB  - Forty faecal samples were tested by RT-PCR using coronavirus consensus primers to
      determine faecal shedding of canine coronavirus (CCoV) and canine respiratory
      coronavirus (CRCoV) in a dog population housed at a rescue centre. Seven samples
      were positive for CCoV while all samples were negative for CRCoV. Sequence
      analysis of five CCoV strains showed a high similarity with transmissible
      gastroenteritis virus (TGEV) at the N-terminus of the spike protein. All strains
      contained an open reading frame for the nonstructural protein 7b, which is not
      present in TGEV, indicating that the strains were related to the previously
      described CCoV strain UCD-1. Two samples contained CCoV strains with 5' spike
      sequences most similar to type II CCoV while one sample was found to contain type
      I CCoV. Primers directed to the N gene allowed specific detection of all CCoV
      strains analysed in this study. This investigation shows that CCoV strains
      containing spike proteins similar to TGEV are present in the UK dog population.
      PCR primers directed to conserved regions of the CCoV genome are recommended for
      detection of CCoV in clinical samples due to high genetic variability.

PMID- 19162100
TI  - A natural tetranortriterpenoid with immunomodulating properties as a potential
      anti-HSV agent.
AB  - Meliacine (MA), an antiviral principle present in partially purified leaf
      extracts of Melia azedarach L., prevents the development of herpetic stromal
      keratitis (HSK) in mice by diminishing the viral load in the eye and the severity
      of lesions caused by a virus-induced immunopathological reaction. The
      tetranortriterpenoid 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), obtained from
      MA purification, displays anti-herpetic activity and impedes nuclear factor
      kappaB (NF-kappaB) activation in HSV-1 infected conjunctival cells. To extend our
      understanding about CDM biological properties, we investigated its anti-HSV-1
      activity as well as the effect on NF-kappaB activation and cytokine secretion
      induced by viral (HSV-1) and no-viral (LPS) stimuli, in corneal cells and
      macrophages. CDM exerted a potent anti-HSV-1 effect on corneal cells and
      inhibited NF-kappaB translocation to the nucleus, leading to a decrease in IL-6
      production. Besides, CDM seemed to modulate IL-6 and TNF-alpha responses in
      macrophages, whether they were infected with HSV-1 or stimulated with LPS.
      However, CDM did not affect NF-kappaB activation in these cells, suggesting that
      an alternative NF-kappaB cell signaling pathway would be involved in the
      modulation of cytokine production. We conclude that, in addition to its antiviral
      effect, CDM would be acting as an immunomodulating compound which would be
      responsible for the improvement of murine HSK already reported.

PMID- 19162101
TI  - PrP(Sc) of scrapie 263K propagates efficiently in spleen and muscle tissues with
      protein misfolding cyclic amplification.
AB  - Transmissible spongiform encephalopathies (TSEs), or prion diseases, are
      transmissible neurodegenerative disorders of protein conformation. This group of
      diseases is caused by infectious agents, termed prions, which can convert normal
      conformation (PrP(C)) into misfolded protein (PrP(Sc)). The infectivity of non
      neuronal tissues has been wildly addressed, but the propagating features and the
      biochemical properties of prion generated from these tissues are only partially
      settled. In this study, utilizing protein misfolding cyclic amplification (PMCA),
      the in vitro conversion of PrP(C) into PrP(Sc) in spleen and muscle tissues can
      be induced by PrP(Sc) produced in vivo. The further propagation of newly formed
      PrP(Sc) in normal brain and some of the biochemical properties of new PrP(Sc) are
      similar as the brain-derived prions, implying the naturally infectious pathway of
      prion from peripheral generation to neuro-invasion. However, compared with the
      brain-derived PrP(Sc), the weaker resistance of new PrP(Sc) to some inactivated
      agents, i.e. sodium hydroxide and thermal inactivation, are observed. Our data
      provide the reliable evidence that the brain-derived PrP(Sc) can utilize the
      PrP(C) from non-neuronal tissues for its propagation. Similarity of the
      replicative ability in PMCA in vitro and the infectivity in vivo highlights the
      possibility to use PMCA instead of bioassay to investigate the propagation of
      prion.

PMID- 19162102
TI  - Protective effects of the complex between manganese porphyrins and catalase
      poly(ethylene glycol) conjugates against hepatic ischemia/reperfusion injury in
      vivo.
AB  - The complex between manganese (Mn) porphyrins and catalase-poly(ethylene glycol)
      (PEG) conjugates has been designed for the protective effect against hepatic
      ischemia/reperfusion injury in vivo. The resulting Mn-porphyrin/catalase-PEG
      complex with dual enzymatic activity of superoxide dismutase (SOD) and catalase
      enhanced the blood circulation. The spin reduction rate in the rats treated with
      the Mn-porphyrin/catalase-PEG complex was significantly higher than that in the
      untreated rats and almost equal to that in the sham group rats. Furthermore, the
      Mn-porphyrin/catalase-PEG complex significantly decreased the serum aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) levels. These results
      suggest that the Mn-porphyrin/catalase-PEG complex exhibited the antioxidative
      activity to protect hepatic ischemia/reperfusion injury in vivo.

PMID- 19162103
TI  - Approaches to enhancing immune responses stimulated by CpG oligodeoxynucleotides.
AB  - CpG oligodeoxynucleotides (ODN) activate the immune system and are promising
      immunotherapeutic agents against infectious diseases, allergy/asthma and cancer.
      It has become apparent that while CpG ODN are potent immune activators in mice,
      their immune stimulatory effects are often less dramatic in humans and large
      animals. This disparity between rodents and mammals has been attributed to the
      differences in TLR9 expression in different species. This along with the
      sometimes transient activity of ODN may limit its potential immunotherapeutic
      applications. Several approaches to enhance the activity of CpG ODN have been
      explored including formulation of ODN in depot-forming adjuvants, and more
      recently, coadministration with polyphosphazenes, inhibitors of cytokines that
      downregulate TLR9 activation, and simultaneous activation with multiple TLR
      agonists. We will discuss these approaches and the mechanisms involved, with
      emphasis on what we have learned from large animal models.

PMID- 19162104
TI  - Remodeled salt appetite in rat offspring by perinatal exposure to nicotine.
AB  - To determine the effect of perinatal exposure to nicotine on water intake and
      salt appetite related to renin-angiotensin system in the offspring, maternal rats
      during perinatal period [gestation (G) or gestation plus lactation (G+L)] were
      subcutaneously administrated with nicotine. Four months after birth, intake of
      1.8% NaCl and water was measured following 24h water deprivation in the adult
      offspring, and angiotensin receptors in the brain were determined. There was no
      change of blood Na(+) and K(+) concentrations following exposure to nicotine
      either during pregnancy or pregnancy plus lactation. To the offspring following
      perinatal exposure to nicotine, their salt appetite was significantly increased
      (during the first 2h and 24h testing periods) by 24h water deprivation. In the
      forebrain of the offspring with history of perinatal exposure to nicotine,
      expression of angiotensin AT(1) and AT(2) subtype was reduced. The results showed
      that spontaneous salt appetite was not changed by using nicotine during perinatal
      periods, while stimulated salt intake could be affected by exposure to nicotine
      in fetal origins, and the changed behavior (water and salt intake) by perinatal
      nicotine was associated with the remodeled expression of AT(1) and AT(2)
      receptors in the forebrain of the offspring.

PMID- 19162105
TI  - GHTD-amide: a naturally occurring beta cell-derived peptide with hypoglycemic
      activity.
AB  - In the early 1970s, a peptide fraction with insulin potentiating activity was
      purified from human urine but the identity and origins of the active constituent
      remained unknown. Here we identify the active component and characterize its
      origins. The active peptide was identified as an alpha amidated tetrapeptide with
      the sequence GHTD-amide. The peptide was synthesized and tested for stimulation
      of glycogen synthesis and insulin potentiation by insulin tolerance testing in
      insulin-deficient rats, which confirmed GHTD-amide as the active peptide. Tissue
      localization using a peptide-specific anti-serum and epifluorescent and confocal
      microscopy showed decoration of pancreatic islets but not other tissues. Confocal
      microscopy revealed co-localization with insulin and immunogold and electron
      microscopy showed localization to dense core secretory granules. Consistent with
      these observations GHTD-amide was found in media conditioned by MIN6 islet beta
      cells. Sequence database searching found no annotated protein in the human
      proteome encoding a potential precursor for GHTD-amide. We conclude that the
      insulin potentiating activity originally described in human urine is attributable
      to the tetrapeptide GHTD-amide. GHTD-amide is a novel peptide produced by
      pancreatic beta cells and no precursor protein is present in the annotated human
      proteome. Stimulation of glycogen synthesis and co-localization with insulin in
      beta cells suggest that GHTD-amide may play a role in glucose homeostasis by
      enhancing insulin action and glucose storage in tissues.

PMID- 19162106
TI  - Inhibition of nNOS reduces ischemic cell death through down-regulating calpain
      and caspase-3 after experimental stroke.
AB  - In vitro nitric oxide (NO) regulates calpain and caspase-3 activation, and in
      vivo neuronal nitric oxide synthase (nNOS), calpain and caspase-3 participate in
      the ischemic brain injury. Our objective was to investigate whether nNOS was
      involved in the ischemic brain injury through activating calpain and caspase-3
      during experimental stroke. Rats received 1-h ischemia by intraluminant filament,
      and then reperfused for 23h (R 23h). nNOS inhibitor 7-nitroindozale (7-NI,
      50mg/kg) was administrated intraperitoneally 5min before ischemia. Our data
      showed that treatment with 7-NI markedly reduced neurological deficits, the brain
      swelling, and the infarct volume at R 23h. Enzyme studies revealed significant
      suppression of the activities of m-calpain and caspase-3 in penumbra and core,
      and the activities of mu-calpain in penumbra, but not in core, in 7-NI-treated
      rats versus vehicle-treated rats. Western blot analysis demonstrated that 7-NI
      markedly increased the levels of MAP-2 and spectrin in penumbra and core compared
      with vehicle-treated rats. Histopathological studies displayed that 7-NI
      significantly reduced the necrotic cell death in penumbra and core, and apoptotic
      cell death in penumbra, but not in core. These data demonstrate the involvement
      of NO produced by nNOS in the ischemic neuronal injury through affecting the
      activation of calpain and caspase-3 in penumbra and core after experimental
      stroke, which provides a new perspective on possible mechanisms of action of nNOS
      inhibition in cerebral ischemia.

PMID- 19162107
TI  - [(11)C]PIB-amyloid binding and levels of Abeta40 and Abeta42 in postmortem brain
      tissue from Alzheimer patients.
AB  - beta-Amyloid (Abeta) deposits are one of the major histopathological hallmarks of
      Alzheimer's disease (AD). The amyloid-imaging positron emission tomography (PET)
      tracer [(11)C]PIB (N-methyl[(11)C]2-(4'-methylaminophenyl)-6-hydroxy
      benzothiazole) is used in the assessment of Abeta deposits in the human brain.
      [(11)C]PIB-amyloid interaction and insoluble Abeta40 and Abeta42 peptide levels
      in the brain were quantified in postmortem tissue from nine AD patients and nine
      age-matched control subjects in the temporal, frontal and parietal cortices and
      the cerebellum. Autoradiographical studies showed significantly higher densities
      of specific [(11)C]PIB-amyloid binding in gray matter in the temporal and
      parietal cortex (62fmol/mg tissue) in AD patients as compared to control
      subjects, whereas the density was somewhat lower in the frontal cortex (56fmol/mg
      tissue). No specific binding could be detected in the AD cerebellum or in the
      tissues from the control subjects (< or =5fmol/mg tissue). Insoluble Abeta40 and
      total Abeta levels (i.e. sum of Abeta40 and Abeta42) were significantly higher in
      patients than in controls in all measured cortical regions as determined using
      ELISA, which was confirmed using immunohistochemistry. The present findings show
      a more regional selective distribution of [(11)C]PIB amyloid binding than
      previously reported. Moreover, it is suggested that some of the [(11)C]PIB
      binding and insoluble Abeta seen in control subjects may be amyloid in the blood
      vessels.

PMID- 19162108
TI  - Identification of novel vaccine candidates for Chagas' disease by immunization
      with sequential fractions of a trypomastigote cDNA expression library.
AB  - The protozoan Trypanosoma cruzi is the etiological agent of Chagas' disease, a
      major chronic infection in Latin America. Currently, there are neither effective
      drugs nor vaccines for the treatment or prevention of the disease. Several T.
      cruzi surface antigens are being tested as vaccines but none of them proved to be
      completely protective, probably because they represent only a limited repertoire
      of all the possible T. cruzi target molecules. Taking into account that the
      trypomastigote stage of the parasite must express genes that allow the parasite
      to disseminate into the tissues and invade cells, we reasoned that genes
      preferentially expressed in trypomastigotes represent potential targets for
      immunization. Here we screened an epimastigote-subtracted trypomastigote cDNA
      expression library by genetic immunization, in order to find new vaccine
      candidates for Chagas' disease. After two rounds of immunization and challenge
      with trypomastigotes, this approach led to the identification of a pool of 28
      gene fragments that improved in vivo protection. Sequence analysis of these
      putative candidates revealed that 19 out of 28 (67.85%) of the genes were
      hypothetical proteins or unannotated T. cruzi open reading frames, which
      certainly would not have been identified by other methods of vaccine discovery.

PMID- 19162109
TI  - A novel vaccine targeting Fusobacterium nucleatum against abscesses and
      halitosis.
AB  - An abscess in a gum pocket, resulting from bacterial infection, is a common
      source of chronic halitosis. Although antibiotics are generally prescribed for
      abscesses, they require multiple treatments with risks of creating resistant
      bacterial strains. Here we develop a novel vaccine using ultraviolet-inactivated
      Fusobacterium nucleatum (F. nucleatum), a representative oral bacterium for
      halitosis. A gum pocket model, established by continuous inoculation of F.
      nucleatum, was employed to validate the vaccine potency. Mice immunized with
      inactivated F. nucleatum effectively minimized the progression of abscesses,
      measured by swollen tissues of gum pockets. Most notably, the immunized mice were
      capable of eliciting neutralizing antibodies against the production of volatile
      sulfur compounds of F. nucleatum. The novel vaccine inducing protective immunity
      provides an alternative option to conventional antibiotic treatments for chronic
      halitosis associated with abscesses.

PMID- 19162110
TI  - Immunotherapy with combined DNA vaccines is an effective treatment for M. bovis
      infection in cattle.
AB  - Mycobacterium bovis causes tuberculosis in cattle. Because current therapies
      inadequately prevent disease spread, new therapies for M. bovis infections are
      urgently needed. We treated M. bovis-infected cattle with combinations of DNA
      vaccines, resulting in significantly reduced pulmonary bacterial loads compared
      with the untreated group. Further, the pathological changes of lungs were also
      slight and the lesions were limited in animals treated with the combined DNA
      vaccines, whereas untreated animals had extensive lung fibrosis and consolidated
      lesions. This is the first report of DNA vaccine used to treat M. bovis. Thus,
      combined DNA vaccines may provide enhanced immunotherapeutic efficacy for
      treatment of bovine tuberculosis.

PMID- 19162111
TI  - KMP-11 DNA immunization significantly protects against L. donovani infection but
      requires exogenous IL-12 as an adjuvant for comparable protection against L.
      major.
AB  - As vaccine potential of cross-species protection by a candidate antigen is less
      explored, in this study we compared cross-specific protective efficacy of
      Kinetoplastid Membrane Protein-11 (KMP-11) as a DNA vaccine alone and in
      conjunction with exogenous IL-12 administration in experimental BALB/c model
      against two most widely prevalent forms of clinical diseases caused by Leishmania
      major (LM) and Leishmania donovani (LD). Whereas, KMP-11 DNA vaccination alone
      showed significant potential in terms of resolution of splenic and hepatic
      parasite burden against virulent LD challenge, it showed considerably less
      efficacy (<70% reduction) against virulent LM challenge in terms of presence of
      parasite in lymph node. Remarkably exogenous IL-12 administration in the form of
      IL-12 p35/p40 expression vectors or recombinant protein along with KMP-11 DNA had
      exactly opposing effect on protection against LM and LD. Exogenous IL-12
      administration significantly increased residual LD-burden but enhanced the
      protective efficacy of KMP-11 DNA vaccine against LM compared to KMP-11
      immunization alone. Elucidation of effector mechanism showed KMP-11 DNA induced
      protection against LD was associated with the generation of mixed Th1/Th2
      response, while KMP-11/IL-12-induced comparable protection against LM was
      associated with high IgG2a titre indicative of a polarized Th1 response.
      Exogenous IL-12 administration resulted in robust gamma interferon (IFN-gamma)
      production and suppression of IL-4 from CD4+ T cell against both LM and LD.
      Nevertheless protective immune response was only compromised against LD infection
      where frequency of anti-KMP-11 CTL response was significantly reduced after
      exogenous IL-12 administration. Our study provides a comparative evaluation of
      effector mechanisms in the assessment of cross-specific protection by KMP-11 and
      KMP-11/IL-12 immunization against these two prevalent forms of leishmaniasis.

PMID- 19162112
TI  - A novel chimpanzee serotype-based adenoviral vector as delivery tool for cancer
      vaccines.
AB  - The use of adenovirus (Ad) as vaccine vectors is hindered by pre-existing
      immunity to human Ads in most of the human population. In order to overcome this
      limitation, uncommon alternative Ad serotypes need to be utilized. In this study,
      an E1-E3 deleted recombinant Ad based on the chimpanzee serotype 3 (ChAd3) was
      engineered to express human carcinoembryonic antigen (CEA) protein or rat neu
      extracellular/transmembrane domains (ECD.TM). ChAd3 vectors were tested in CEA
      transgenic (CEA.Tg) and BALB/NeuT mice, which show immunologic tolerance to these
      antigens. ChAd3 is capable of inducing an immune response comparable to that of
      hAd5 serotype-based vectors, thus breaking tolerance to tumor associated antigens
      (TAAs) and achieving anti-tumor effects. Of importance is that ChAd3 can overcome
      hAd5 pre-existing immunity and work in conjunction with DNA electroporation (DNA
      EP) and other Ad vaccines based on common human serotypes.

PMID- 19162113
TI  - Immunological assessment of plant-derived avian flu H5/HA1 variants.
AB  - Polypeptide variants of the HA1 antigenic domain of the H5N1 avian influenza
      virus hemagglutinin (HA) molecule were produced in plants using transient and
      stable expression systems and fused with His/c-myc tags or with mouse or human Fc
      antibody fragments. The resulting peptides were purified and used for
      intramuscular immunization of mice. While the recombinant HA1 variants induced a
      significant serum humoral immune response in the mice, none of the HA1
      preparations induced virus-neutralizing antibodies. Fusion with the Fc fragment
      improved overall yield of the constructs and allowed purification requiring only
      a single step, but led to no detectable fusion-related enhancement of
      immunogenicity or quality of immune response.

PMID- 19162114
TI  - Successful co-administration of a human rotavirus and oral poliovirus vaccines in
      Bangladeshi infants in a 2-dose schedule at 12 and 16 weeks of age.
AB  - Co-administration of oral live-attenuated human rotavirus vaccine RIX4414
      (Rotarix) and oral polio vaccine (OPV) was assessed. Healthy infants were
      randomised to receive 2-doses of either: RIX4414 or placebo co-administered with
      OPV (12 and 16 weeks of age); or RIX4414 or placebo given 15 days after OPV.
      After vaccination, 56.5-66.7% of RIX4414 and 18.6% of placebo recipients had
      seroconverted for rotavirus IgA. No significant differences between RIX4414
      groups with or without OPV co-administration were observed. No statistically
      significant differences were observed between groups for polio seroprotection
      rates. RIX4414 vaccine was immunogenic when co-administered with OPV and did not
      interfere with OPV seroprotection rates.

PMID- 19162115
TI  - Long-term persistence of tick-borne encephalitis antibodies in children 5 years
      after first booster vaccination with Encepur Children.
AB  - Tick-borne encephalitis (TBE) is a serious viral infection, which can lead to
      permanent neurological sequelae in children. The incidence of TBE disease is
      increasing in many European countries and is particularly pronounced in some
      regional populations. Vaccination is the most effective method for preventing TBE
      disease and is recommended for all those living and working in TBE-endemic areas.
      Encepur Children is licensed for TBE vaccination in children 1-11 years of age.
      Following primary vaccination, booster vaccinations are recommended; however, the
      optimal timing for booster vaccination of children is not known. The aim of this
      study was to assess the persistence of TBE antibodies in children at 3 and 5
      years after their first booster vaccination with Encepur Children and to re
      evaluate booster vaccination recommendations. Children 1-11 years of age (n=335)
      who received primary TBE vaccination according to the rapid schedule (Days 0, 7,
      and 21) in a previous study received a booster vaccination 12-18 months later,
      and were invited for follow-up at 3 and 5 years post-booster. TBE antibodies were
      measured using a virus neutralization test (NT; in-house, Novartis Vaccines) and
      also using anti-TBE IgG ELISA (Enzygnost, Siemens, Germany). In this analysis,
      275 of 278 (99%) subjects and all 190 (100%) subjects who completed the follow-up
      at 3 and 5 years, respectively, had NT titres > or = 10. Likewise, all 275 of 278
      (99%) and 188 of 190 (99%) subjects tested positive by ELISA at 3 and 5 years
      after the booster vaccination, respectively. Based on serological data, the
      interval for subsequent booster vaccinations with Encepur Children can be
      extended from 3 to 5 years after receiving primary vaccination and a first
      booster vaccination 12-18 months later.

PMID- 19162116
TI  - Hepatitis A vaccination coverage among adults aged 18-49 years in the United
      States.
AB  - BACKGROUND: Hepatitis A is the most common type of hepatitis reported in the
      United States. Prior to hepatitis A vaccine introduction in 1996, hepatitis A
      incidence followed a cyclic pattern with peak incidence occurring every 10-15
      years. During 1980-1995, between 22,000 and 36,000 hepatitis A cases were
      reported annually. Since 1996, hepatitis A vaccination recommendations have
      included adults at risk for infection and children living in communities with the
      highest disease rates. This study provides the first national estimates of self
      reported hepatitis A vaccination coverage among persons aged 18-49 years in the
      United States. METHODS: We analyzed the 2007 National Immunization Survey-Adult
      (NIS-Adult) data with restrictions to individuals aged 18-49 years. National
      estimates of hepatitis A vaccination coverage were calculated based on self
      report and multivariable logistic regression analysis was used to identify
      factors independently associated with hepatitis A vaccination status. RESULTS:
      Among adults aged 18-49 years, 12.1% (95% confidence interval, CI=9.9-14.8%) had
      received two or more doses of hepatitis A vaccine in 2007. Hepatitis A
      vaccination coverage was significantly higher among adults aged 18-29 years
      (15.6%) and adults aged 30-39 years (12.9%) compared with adults aged 40-49 years
      (8.3%). Coverage was significantly lower for Hispanics (7.1%) compared with non
      Hispanic whites (12.5%). Characteristics independently associated with a higher
      likelihood of hepatitis A vaccination among persons aged 18-49 years included
      younger age groups, persons at or above poverty level, persons with public
      medical insurance, and persons who received influenza vaccination in the past
      season. CONCLUSIONS: In 2007, self-reported hepatitis A vaccination coverage
      among adults aged 18-49 years was 12.1%. These data provide the first national
      hepatitis A vaccination coverage estimates among adults and are very important in
      planning and implementing strategies for increasing hepatitis A vaccination
      coverage among adults at risk for hepatitis A.

PMID- 19162117
TI  - Prevalence and sequence variations of the genes encoding the five antigens
      included in the novel 5CVMB vaccine covering group B meningococcal disease.
AB  - During the recent years, projects are in progress for designing broad-range non
      capsular-based meningococcal vaccines, covering also serogroup B isolates. We
      have examined three genes encoding antigens (NadA, GNA1030 and GNA2091) included
      in a novel vaccine, i.e. the 5 Component Vaccine against Meningococcus B (5CVMB),
      in terms of gene prevalence and sequence variations. These data were combined
      with the results from a similar study, examining the two additional antigens
      included in the 5CVMB (fHbp and GNA2132). nadA and fHbp v. 1 were present in 38%
      (n=36), respectively 71% (n=67) of the isolates, whereas gna2132, gna1030 and
      gna2091 were present in all the Neisseria meningitidis isolates tested (n=95).
      The level of amino acid conservation was relatively high in GNA1030 (93%),
      GNA2091 (92%), and within the main variants of NadA and fHbp. GNA2132 (54% of the
      amino acids conserved) appeared to be the most diversified antigen. Consequently,
      the theoretical coverage of the 5CVMB antigens and the feasibility to use these
      in a broad-range meningococcal vaccine is appealing.

PMID- 19162118
TI  - Properties of gap junction blockers and their behavioural, cognitive and
      electrophysiological effects: animal and human studies.
AB  - Gap junctions play an important role in brain physiology. They synchronize
      neuronal activity and connect glial cells participating in the regulation of
      brain metabolism and homeostasis. Gap junction blockers (GJBs) include various
      chemicals that impair gap junction communication, disrupt oscillatory neuronal
      activity over a wide range of frequencies, and decrease epileptic discharges. The
      behavioural and clinical effects of GJBs suggest that gap junctions can be
      involved in the regulation of locomotor activity, arousal, memory, and breathing.
      Severe neuropsychiatric side effects suggest the involvement of gap junctions in
      mechanisms of consciousness. Unfortunately, the available GJBs are not selective
      and can bind to targets other than gap junctions. Other problems in behavioural
      studies include the possible adverse effects of GJBs, for example, retinal
      toxicity and hearing disturbances, changes in blood-brain transport, and the
      metabolism of other drugs. Therefore, it is necessary to design experiments
      properly to avoid false, misleading or uninterpretable results. We review the
      pharmacological properties and electrophysiological, behavioural and cognitive
      effects of the available gap junction blockers, such as carbenoxolone,
      glycyrrhetinic acid, quinine, quinidine, mefloquine, heptanol, octanol,
      anandamide, fenamates, 2-APB, several anaesthetics, retinoic acid, oleamide,
      spermine, aminosulfonates, and sodium propionate. It is concluded that despite a
      number of different problems, the currently used gap junction blockers could be
      useful tools in pharmacology and neuroscience.

PMID- 19162119
TI  - TPH2 -703G/T SNP may have important effect on susceptibility to suicidal behavior
      in major depression.
AB  - BACKGROUND: Serotonergic system-related genes can be good candidate genes for
      both major depressive disorder (MDD) and suicidal behavior. In this study, we
      aimed to investigate the association of serotonin 2A receptor gene -1438A/G SNP
      (HTR2A -1438A/G), tryptophan hydroxylase 2 gene -703G/T SNP (TPH2 -703G/T) and
      serotonin 1A receptor C-1019G (HTR1A C-1019G) with suicidal behavior. METHODS:
      One hundred and eighty one suicidal depressed patients and 143 non-suicidal
      depressed patients who met DSM-IV criteria for major depressive disorder were
      recruited from patients who were admitted to Korea University Ansan Hospital. One
      hundred seventy six normal controls were healthy volunteers who were recruited by
      local advertisement. Patients and normal controls were genotyped for HTR2A 
      1438A/G, TPH2 -703G/T and 5-HT1A C-1019G. The suicidal depressed patients were
      evaluated by the lethality of individual suicide attempts using Weisman and
      Worden's risk-rescue rating (RRR) and the Lethality Suicide Attempt Rating Scale
      updated (LSARS-II). In order to assess the severity of depressive symptoms of
      patients, Hamilton's Depression Rating Scale (HDRS) was administered. Genotype
      and allele frequencies were compared between groups by chi(2) statistics.
      Association of genotype of the candidate genes with the lethality of suicidal
      behavior was examined with ANOVA by comparing the mean scores of LSARS and RRR
      according to the genotype. RESULTS: There were statistically significant
      differences in the genotype distributions and allele frequencies of TPH2 -703G/T
      between the suicidal depressive group and the normal control group. The
      homozygous allele G (G/G genotype) frequency was significantly higher in suicidal
      depressed patients than in controls. However, no differences in either genotype
      distribution or in allele frequencies of HTR2A -1438A/G and HTR1A C-1019G were
      observed between the suicidal depressed patients, the non-suicidal depressed
      patients, and the normal controls. There were no differences in the lethality of
      suicidal behavior in suicidal depressed patients according to the genotypes of
      three polymorphisms. CONCLUSION: Our results suggest that TPH2 -703G/T SNP may
      have an important effect on susceptibility to suicidal behavior. Furthermore, an
      increased frequency of G allele of TPH2 SNP may be associated with elevated
      suicidal behavior itself rather than with the diagnosis of major depression and
      may increase risk of suicidality, independent of diagnosis.

PMID- 19162120
TI  - Aripiprazole-induced sialorrhea.

PMID- 19162121
TI  - SAT-1 -1415T/C polymorphism and susceptibility to schizophrenia.
AB  - Patients suffering from psychosis show increased blood and fibroblast total
      polyamine levels. Spermidine/spermine N1-acetyltransferase (SSAT-1) and its
      coding gene (SAT-1) are the main factors regulating polyamine catabolism. The aim
      of the present study was to examine the association between the SAT-1 -1415T/C
      single nucleotide polymorphism (SNP) and schizophrenia. A case-control design was
      used in order to compare the genotypes for the SNP between schizophrenia patients
      (n=180, 83 females and 97 males), other non-psychotic psychiatric patients
      (n=413, 256 females and 157 males), and healthy controls (n=251, 101 females and
      150 males). No significant differences in the distribution of the genotypes of
      the SAT-1 -1415T/C SNP were found groups among groups. We failed to demonstrate a
      significant association between the SAT-1 -1415T/C SNP and schizophrenia, but a
      mild association between allele C and psychopathology was found in the female
      group.

PMID- 19162122
TI  - Concentrations of polybrominated diphenyl ethers, hexachlorobenzene and
      polycyclic aromatic hydrocarbons in various foodstuffs before and after cooking.
AB  - The cooking-induced changes in the levels of polybrominated diphenyl ethers
      (PBDEs), hexachlorobenzene (HCB), and 16 polycyclic aromatic hydrocarbons (PAHs)
      in various foodstuffs were investigated. Foods included fish (sardine, hake and
      tuna), meat (veal steak, loin of pork, breast and thigh of chicken, and steak and
      rib of lamb), string bean, potato, rice, and olive oil. For each food item, raw
      and cooked (fried, grilled, roasted, boiled) samples were analyzed. There were
      some variations in the concentrations of PBDEs before and after cooking. However,
      they depended not only on the cooking process, but mainly on the specific food
      item. The highest HCB concentrations were found in sardine, being lower in cooked
      samples. All cooking processes enhanced HCB levels in hake, while very scarce
      differences could be noted in tuna (raw and cooked). In general terms, the
      highest PAH concentrations were found after frying by being the values especially
      notable in fish, excepting hake, where the highest total PAH levels corresponded
      to roasted samples. The results of this study show that, in general, cooking
      processes are only of a limited value as a means of reducing PBDE, HCB and PAH
      concentrations in food.

PMID- 19162123
TI  - A method to rank order water soluble compounds according to their toxicity using
      Caenorhabditis elegans, a Complex Object Parametric Analyzer and Sorter, and
      axenic liquid media.
AB  - Complex Object Parametric Analyzer and Sorter (COPAS) parameters Time of Flight
      (TOF) and Extinction (EXT) were utilized to assess growth and development in
      Caenorhabditis elegans exposed to (in order of decreasing toxicity) sodium
      arsenite, sodium fluoride, caffeine, valproic acid, sodium borate or DMSO in C.
      elegans Habitation Medium (CeHM) for 72h. Using multivariate statistical modeling
      and unique sub sampling procedures mean p-value ratios were calculated for each
      compound. Comparison of mean p-value ratios and/or the percent change in mean-p
      value ratios to controls were utilized to assess test compound toxicity. Using
      this assay 5 of the 6 compounds tested (83.3%) were correctly ranked according to
      their toxicity based on oral rat LD50 data. Test compounds were ranked from most
      toxic to least toxic as follows: sodium arsenite, sodium fluoride, sodium borate,
      valproic acid, caffeine and DMSO. Sodium borate was found to be more toxic than
      caffeine and valproic acid in this bioassay. This study suggests that axenic
      liquid culture may be used to expose large numbers of nematodes to water soluble
      toxicants and the COPAS parameters TOF and EXT may be used as functional
      biomarkers to assess a toxin's effect on growth and development in C. elegans.

PMID- 19162124
TI  - Depression and reduced sensitivity to non-rewards versus rewards: Evidence from
      event-related potentials.
AB  - Depression has been characterized in recent years in terms of deficits in
      positive affect and an underactive approach-related motivational system.
      Consistent with this view, behavioral and electrocortical studies suggest that
      reduced sensitivity to rewards may be a fundamental feature of depression. Within
      the event-related potential literature, the feedback negativity (FN) has been
      identified as a component that is sensitive to feedback indicating non-rewards
      versus rewards, and has been linked to phasic changes in midbrain dopamine levels
      that indicate whether events are better or worse than expected; thus, the FN may
      be a useful marker for abnormalities in reward sensitivity associated with
      depression. In the current study, a simple gambling task was used to elicit an FN
      in participants, and the magnitude of the FN was related to levels of depressive
      symptoms, as well as levels of anxiety and stress. The enhancement of the FN to
      non-rewards relative to rewards was found to be inversely related to depression
      and stress reactivity; only the relationship between the FN and stress remained
      significant after controlling for the other psychological variables. The P3 to
      feedback, meanwhile, was inversely related to depression and anxiety scores
      regardless of feedback type. These results are discussed within the context of
      current models of depression and reward sensitivity.

PMID- 19162125
TI  - Auto-/heterotrophic endosymbiosis evolves in a mature stage of ecosystem
      development in a microcosm composed of an alga, a bacterium and a ciliate.
AB  - We investigate an ecological mechanism by which endosymbiotic associations
      evolve, with a particular focus on the relationship between the evolution of
      endosymbiosis between auto- and heterotrophic organisms, and the stages of
      ecosystem development. For this purpose we conducted a long-term microcosm
      culture composed of three species, a green alga (Chlorella vulgaris), a bacterium
      (Escherichia coli), and a ciliated protozoan (Tetrahymena thermophila) for 3
      years. During this culture T. thermophila cells harboring Chlorella cells emerged
      by phagocytotic uptake, and increased in frequency, reaching ca. 80-90%. This
      level was maintained in the late stage of ecosystem dynamics. Analysis of the
      ecosystem dynamics in the microcosm revealed that a complex causal process
      through direct/indirect interactions among ecosystem components led to reduction
      in dissolved O2 and food (E. coli) available to the T. thermophila, which gave a
      selective advantage to the organisms in the endosymbiotic association. This
      result suggests that the endosymbiosis evolves in a mature stage of ecosystem
      development, where reproduction and survival of prospective partner organisms is
      highly resource-limited and density-dependent, favoring efficient matter/energy
      transfers among participating organisms due to physical proximity. Consequently,
      a complex web of interactions and pathways of matter/energy flow in ecosystem
      evolves from an initially simple one.

PMID- 19162127
TI  - Endothelin-1 stimulates interleukin-6 secretion from 3T3-L1 adipocytes.
AB  - BACKGROUND: Since both endothelin-1 (ET-1) and interleukin-6 (IL-6) may induce
      insulin resistance and adipose tissue is a major contributor of circulating IL-6,
      we examined the effects of ET-1 on IL-6 secretion from 3T3-L1 adipocytes.
      METHODS: IL-6 release was measured by ELISA. RT-PCR and real-time PCR analyses
      were used to determine cellular IL-6 mRNA levels. A luciferase reporter driven by
      promoter (-1310/+198) of mouse IL-6 gene was transfected into 3T3-L1 adipocytes
      to monitor IL-6 transcription. RESULTS: Treatment of adipocytes with ET-1 dose-
      and time-dependently increased IL-6 secretion. The stimulatory effect of ET-1 on
      IL-6 secretion was abolished by actinomycin D and ET-1 induced an increase in IL
      6 mRNA levels. ET-1 was able to enhance the IL-6 promoter activity and its
      stimulatory effect was inhibited by GF109203X, U0126, salicylate, dominant
      negative CREB and mithramycin A. Thus it appears that ET-1 may stimulate IL-6
      secretion mainly through an enhanced IL-6 transcription, by a mechanism involving
      both protein kinase C and p42/p44 mitogen-activated protein kinase, and probably
      downstream NF-kappaB, CREB and Sp1 transcription factors. GENERAL SIGNIFICANCE:
      This study demonstrates that ET-1 is able to increase IL-6 secretion from
      adipocytes and raises the possibility that ET-1-induced insulin resistance may be
      mediated by IL-6.

PMID- 19162126
TI  - Seed in soil, with an epigenetic view.
AB  - It is becoming increasingly evident that discrete genetic alterations in
      neoplastic cells alone cannot explain multistep carcinogenesis whereby tumor
      cells are able to express diverse phenotypes during the complex phases of tumor
      development and progression. The epigenetic model posits that the host
      microenvironment exerts an initial, inhibitory constraint on tumor growth that is
      followed by acceleration of tumor progression through complex cell-matrix
      interactions. This review emphasizes the epigenetic aspects of breast cancer
      development in light of such interactions between epithelial cells ("seed") and
      the tumor microenvironment ("soil"). Our recent research findings suggest that
      epigenetic perturbations induced by the tumor microenvironment may play a causal
      role in promoting breast cancer development. It is believed that abrogation of
      these initiators could offer a promising therapeutic strategy.

PMID- 19162128
TI  - At the crossroads of T helper lineage commitment-Epigenetics points the way.
AB  - The immune system has the capacity to respond to various types of pathogens
      including bacteria, viruses, tumors and parasites. This requires a flexible
      immune system, which in part depends on the development of alternative effector T
      helper cells, with different cytokine repertoires that direct the overall immune
      response. The reciprocal effects of the T helper subtypes Th1 and Th2 are well
      documented, but the mechanisms involved in alternative cytokine expression and
      silencing are less well defined. Introduction of advances within the field of
      chromatin folding and epigenetic regulation of transcription has begun to explain
      some of the fundamental principles of T helper cell development. In addition,
      epigenetic regulation has proven essential also for the more recently discovered
      T helper cell subtypes; regulatory T cells and the Th17 lineage. As the
      importance of proper epigenetic regulation becomes evident, attention is also
      focused on the potential harmfulness of epigenetic dysregulation. Autoimmunity
      and allergy are two clinical situations that have been implicated as results of
      imperfect cytokine silencing. This review will address recent advances in the
      field of epigenetic regulation of T lymphocytes and their maturation from naive
      cells into different effector T cell lineages. In particular, epigenetic
      involvement in regulation of key effector cytokines and specific transcription
      factors determining the CD4(+) T lymphocyte lineage commitment will be discussed.

PMID- 19162129
TI  - Rho GTPases in hepatocellular carcinoma.
AB  - Rho GTPases are major regulators of signal transduction pathways and play key
      roles in processes including actin dynamics, cell cycle progression, cell
      survival and gene expression, whose deregulation may lead to tumorigenesis. A
      growing number of in vitro and in vivo studies using tumor-derived cell lines,
      primary tumors and animal cancer models strongly suggest that altered Rho GTPase
      signaling plays an important role in the initiation as well as in the progression
      of hepatocellular carcinoma (HCC), one of the deadliest human cancers in the
      world. These alterations can occur at the level of the GTPases themselves or of
      one of their regulators or effectors. The participation into the tumorigenic
      process can occur either through the over-expression of one of these components
      which presents an oncogenic activity as illustrated with RhoA and C or through
      the attenuation of the expression of a component presenting tumor suppressor
      activity as for Cdc42 or the RhoGAP, DLC-1. Consequently, these observations
      reflect the heterogeneity and the complexity of liver carcinogenesis. Recently,
      pharmacological approaches targeting Rho GTPase signaling have been used in HCC
      derived models with relative success but remain to be validated in more
      physiologically relevant systems. Therefore, therapeutic approaches targeting Rho
      GTPase signaling may provide a novel alternative for anti-HCC therapy.

PMID- 19162130
TI  - Sex-specific 24-h acetylcholine release profile in the medial prefrontal cortex:
      simultaneous measurement of spontaneous locomotor activity in behaving rats.
AB  - The difference in visual object recognition by males and females suggests a sex
      specific function in the medial prefrontal cortex (mPFC). In the present study,
      we performed an in vivo microdialysis study in three groups of rats (males,
      diestrous females, and proestrous females) to examine the potential sex
      difference in acetylcholine (ACh) release in the mPFC. The dialysate was
      automatically collected from the mPFC every 20 min for 24 h under freely moving
      conditions and the spontaneous locomotor activity was simultaneously monitored.
      Although ACh release in the mPFC during the dark phase was significantly greater
      than during the light phase in both sexes, the female rats consistently exhibited
      a significantly greater mean ACh release than the males. Spontaneous locomotor
      activity during the dark phase was also significantly greater than during the
      light phase in both sexes, but the females exhibited significantly greater
      spontaneous locomotor activity than the males. In addition, both sexes of rats
      were found to have significant positive correlations between ACh release and
      spontaneous locomotor activity, but females were found to have significantly
      greater correlation coefficients than males. Stereological methods were used to
      examine the number of choline acetyltransferase immunoreactive cells in the
      nucleus basalis magnocellularis and the horizontal diagonal band of Broca. The
      number of choline acetyltransferase immunoreactive cells in the nucleus basalis
      magnocellularis was also greater in females than males, suggesting a contribution
      to the higher ACh release in females. In contrast, no sex difference in the
      choline acetyltransferase immunoreactive cells was observed in the horizontal
      diagonal band of Broca. This is the first report to show a sex difference in the
      24-h ACh release profile in the mPFC of behaving rats.

PMID- 19162131
TI  - The cerebellum and eye-blink conditioning: learning versus network performance
      hypotheses.
AB  - Classical conditioning of the eye-blink reflex in the rabbit is a form of motor
      learning that is uniquely dependent on the cerebellum. The cerebellar learning
      hypothesis proposes that plasticity subserving eye-blink conditioning occurs in
      the cerebellum. The major evidence for this hypothesis originated from studies
      based on a telecommunications network metaphor of eye-blink circuits. These
      experiments inactivated parts of cerebellum-related networks during the
      acquisition and expression of classically conditioned eye blinks in order to
      determine sites at which the plasticity occurred. However, recent evidence
      revealed that these manipulations could be explained by a network performance
      hypothesis which attributes learning deficits to a non-specific tonic dysfunction
      of eye-blink networks. Since eye-blink conditioning is mediated by a
      spontaneously active, recurrent neuronal network with strong tonic interactions,
      differentiating between the cerebellar learning hypothesis and the network
      performance hypothesis represents a major experimental challenge. A possible
      solution to this problem is offered by several promising new approaches that
      minimize the effects of experimental interventions on spontaneous neuronal
      activity. Results from these studies indicate that plastic changes underlying eye
      blink conditioning are distributed across several cerebellar and extra-cerebellar
      regions. Specific input interactions that induce these plastic changes as well as
      their cellular mechanisms remain unresolved.

PMID- 19162132
TI  - Deficits in development of synaptic plasticity in rat dorsal striatum following
      prenatal and neonatal exposure to low-dose bisphenol A.
AB  - Prenatal and neonatal exposure to relatively low-dose bisphenol-A (BPA, 20
      microg/kg/day) causes hyper-locomotion of male rat offspring. This research
      investigated the developmental pattern of activity-dependent synaptic plasticity
      in dorsolateral (DL) striatum, a cellular basis for motor controlling, in male
      rat offspring with hyper-locomotion. High frequency stimulation (four-pulse
      bursts at 100 Hz) was undertaken to induce long-term potentiation (LTP) and long
      term depression (LTD) in corticostriatal synapse during postnatal day (PD) 10-32.
      Herein, we show that in control rats HFS induces LTP during PD12-14 and LTD
      during PD24-32. Strikingly, the prenatal and neonatal exposure to low-dose BPA
      resulted in delay of LTP induction during PD21-32, showing a reversal of LTD
      induction. In addition, in PD28 BPA-rats basal population spike amplitude was
      increased with reduction of paired-pulse facilitation (PPF) compared to the same
      age control rats. Acute application of the dopamine 1 receptor (D1R) antagonist
      SCH23390 in slices obtained from PD28 BPA-rats inhibited not only the PS
      potentiation and PPF-induction but also the induction of LTP. Furthermore, the
      dopamine 2 receptor (D2R) agonist quinpirole recovered the LTD induction in PD28
      BPA-rats, which was D1R-dependent and metabotropic glutamate receptor-dependent.
      In PD28 control rats, the blockade of D2R by l-sulpiride reversed the D1R- and
      mGluR-dependent LTD to short-term potentiation. Therefore, the findings provide
      functional evidence that prenatal and neonatal exposure to low-dose BPA causes
      deficits in development of LTP and LTD at DL-striatum via altering the function
      of dopaminergic receptors.

PMID- 19162133
TI  - Functional tetrodotoxin-resistant Na(+) channels are expressed presynaptically in
      rat dorsal root ganglia neurons.
AB  - The tetrodotoxin-resistant (TTX-R) voltage-gated Na(+) channels Na(v)1.8 and
      Na(v)1.9 are expressed by a subset of primary sensory neurons and have been
      implicated in various pain states. Although recent studies suggest involvement of
      TTX-R Na(+) channels in sensory synaptic transmission and spinal pain processing,
      it remains unknown whether TTX-R Na(+) channels are expressed and function
      presynaptically. We examined expression of TTX-R channels at sensory synapses
      formed between rat dorsal root ganglion (DRG) and spinal cord (SC) neurons in a
      DRG/SC co-culture system. Immunostaining showed extensive labeling of presynaptic
      axonal boutons with Na(v)1.8- and Na(v)1.9-specific antibodies. Measurements
      using the fluorescent Na(+) indicator SBFI demonstrated action potential-induced
      presynaptic Na(+) entry that was resistant to tetrodotoxin (TTX) but was blocked
      by lidocaine. Furthermore, presynaptic [Ca(2+)](i) elevation in response to a
      single action potential was not affected by TTX in TTX-resistant DRG neurons.
      Finally, glutamatergic synaptic transmission was not inhibited by TTX in more
      than 50% of synaptic pairs examined; subsequent treatment with lidocaine
      completely blocked these TTX-resistant excitatory postsynaptic currents. Taken
      together, these results provide evidence for presynaptic expression of functional
      TTX-R Na(+) channels that may be important for shaping presynaptic action
      potentials and regulating transmitter release at the first sensory synapse.

PMID- 19162134
TI  - In situ hybridization study of the distribution of choline acetyltransferase mRNA
      and its splice variants in the mouse brain and spinal cord.
AB  - Choline acetyltransferase is the enzyme that catalyzes the biosynthesis of the
      neurotransmitter acetylcholine. Seven types of mRNA for choline acetyltransferase
      that differ in the 5'-noncoding region are transcribed from the cholinergic gene
      locus from different promoter regions and produced by alternative splicing in the
      mouse. Digoxigenin-labeled riboprobes and in situ hybridization histochemistry
      were used to investigate the expression of N1, R1, R2, R3, R4 and total choline
      acetyltransferase mRNA in the mouse CNS. The relative levels of choline
      acetyltransferase transcripts differed dramatically in distinct subdivisions of
      the mature cholinergic nervous system. Neurons hybridizing with antisense
      riboprobes for all of the five investigated splice variants (R1, R2, R3, R4 and
      N1) as well as those hybridizing with riboprobe for the common protein-coding
      region were found in a number of expected regions in the CNS. They include the
      basal forebrain, striatum, pontomesencephalic tegmentum, motor and autonomic
      nuclei of the brainstem, and spinal cord. Neurons with a moderate to very high
      level of expression of R1 and R2 splice variants were distributed in both the
      forebrain and brainstem nuclei. On the other hand, R3, R4 and N1 splice variants
      revealed a moderate to high level of expression in the brainstem motor and
      autonomic nuclei and ventral and lateral horns of the spinal cord compared to a
      low expression level in forebrain cholinergic structures. No expression of the
      N1, R1, R2, R3 and R4 splice variants was detectable in the neurons of the
      cerebral cortex, hippocampus and medial habenular nucleus. With the riboprobe for
      the common protein-coding region, the neurons of the medial habenular nucleus
      could be labeled at high level, while intrinsic cortical neurons were labeled at
      low level. Hippocampus revealed no significant hybridization for total choline
      acetyltransferase mRNA. These findings strongly suggested that: (1) R1 and R2
      were the major splice variants expressed in the neurons of forebrain nuclei; (2)
      R1, R2, R3, R4 and N1 splice variants were almost equally expressed in the
      brainstem motor and autonomic nuclei and ventral and lateral horns of the spinal
      cord; (3) inferring from a paucity of other isoforms, M type choline
      acetyltransferase mRNA is a splice variant predominantly expressed in the
      cerebral cortex and medial habenular nucleus.

PMID- 19162135
TI  - Phencyclidine affects firing activity of basolateral amygdala neurons related to
      social behavior in rats.
AB  - Negative symptoms of schizophrenia, such as social withdrawal and blunted affect,
      usually persist for a long period, making rehabilitation difficult. Many studies
      have demonstrated a close relationship between function of the amygdala and
      social behavior. Normal social behavior is disturbed in animals administered
      phencyclidine (PCP), which is now considered a reliable pharmacological model of
      schizophrenia. Recent studies have reported that disruption of social behavior in
      PCP-treated rats involved dysfunction of the amygdala. Disturbance of function of
      the amygdala has also been reported in schizophrenic patients. However, no study
      has yet examined the effects of PCP on the firing activity of amygdala neurons.
      In the present study, we recorded the unit activity of basolateral amygdala
      neurons while rats engaged in socially interactive behavior. After identifying
      the response properties of recorded neurons, we then recorded the same neurons
      with systemic PCP administration. Approximately half of the neurons recorded from
      exhibited an increase in spontaneous discharge rate during social interaction.
      Only a few neurons exhibited suppression of discharge rate during social
      interaction. Systemic administration of PCP induced long-lasting activation in
      half of the neurons that exhibited an increase in firing rate during social
      interaction. PCP activated half of basolateral amygdala neurons related to
      socially interactive behavior, and might in this fashion produce dysfunction of
      social behavior.

PMID- 19162136
TI  - Dopaminergic modulation of motor maps in rat motor cortex: an in vivo study.
AB  - While the primary motor cortex (M1) is know to receive dopaminergic projections,
      the functional role of these projections is poorly characterized. Here, it is
      hypothesized that dopaminergic signals modulate M1 excitability and somatotopy,
      two features of the M1 network relevant for movement execution and learning. To
      test this hypothesis, movement responses evoked by electrical stimulation using
      an electrode grid implanted epidurally over the caudal motor cortex (M1) were
      assessed before and after an intracortical injection of D1- (R-(+),8-chloro,7
      hydroxy,2,3,4,5,-tetra-hydro,3-methyl,5-phenyl,1-H,3-benzazepine maleate, SCH
      23390) or D2-receptor (raclopride) antagonists into the M1 forelimb area of rats.
      Stimulation mapping of M1 was repeated after 24 h. D2-inhibition reduced the size
      of the forelimb representation by 68.5% (P<0.001). Movements thresholds, i.e.,
      minimal currents required to induce movement responses increased by 37.5%
      (P<0.001), and latencies increased by 35.9% (P<0.01). Twenty-4 h after the
      injections these effects were reversed. No changes were observed with D1
      antagonist or vehicle. By enhancing intracortical excitability and signal
      transduction, D2-mediated dopaminergic signaling may affect movement execution,
      e.g. by enabling task-related muscle activation synergies, and learning.

PMID- 19162137
TI  - Toll-like receptor-2, CD14 and heat-shock protein 70 in inflammatory lesions of
      rat experimental autoimmune neuritis.
AB  - Experimental autoimmune neuritis (EAN) is a well-known animal model of Guillain
      Barre syndrome (GBS) characterized by inflammation and demyelination in the
      peripheral nervous system. Toll-like receptors (TLRs) together with their co
      receptors form the first line of the self-defense, and play important roles in
      innate immune responses and inflammation. TLRs can be activated by endogenous
      ligands, like heat shock protein 70 (HSP70). In this study, we examined the
      spatiotemporal expressions of TLR2, CD14 and Hsp70 in EAN rats using
      immunohistochemistry and RT-PCR. A significant up-regulation of TLR2, CD14 and
      Hsp70 was seen in sciatic nerves of EAN rats and correlated with disease
      severity. Furthermore, activated macrophages were the main cellular resource of
      TLR2, CD14 and Hsp70 in EAN. Our results suggest that TLR2-, CD14- or Hsp70-based
      immunomodulation might have potential in the control of unwanted innate immune
      system activation in inflammatory neuropathies.

PMID- 19162139
TI  - Paradoxical facilitation of pentylenetetrazole-induced convulsion susceptibility
      in mice lacking neuronal nitric oxide synthase.
AB  - The major aim of this study was to elucidate the relationship between nitric
      oxide (NO) and generalized epilepsy. Mice lacking the neuronal nitric oxide
      synthase (nNOS) gene (nNOS(-/-)) were used in this study to determine the
      relationship between nNOS alpha and NO in pentylentetrazole (PTZ)-induced
      convulsions. nNOS(-/-) mice exhibited severe convulsions following injection with
      a subconvulsive dose of PTZ (40 mg/kg i.p.) and convulsive doses were lethal in
      all of the mice (60 mg/kg i.p.) following tonic convulsions. The results were
      confirmed by using selective nNOS inhibitors in wild-type (nNOS(+/+)) mice. The
      higher doses of the nNOS inhibitors 1-[2-(trifluoromethyl)phenyl] imidazole
      (TRIM) and 3-bromo-7-nitroindazole (3Br7NI) inhibited clonic-tonic convulsions
      induced by a convulsive dose of PTZ (60 mg/kg) in nNOS(+/+) mice. In contrast,
      either TRIM or 3Br7NI at lower doses enhanced convulsions following injection
      with a subconvulsive dose of PTZ (40 mg/kg) in nNOS(+/+) mice similar to nNOS(-/
      ) mice treated with PTZ. Such a proconvulsant effect was observed in nNOS(+/+)
      mice pretreated with nNOS inhibitors but not other NOS inhibitors. These results
      indicate that NO may be regarded as an anticonvulsant or a proconvulsant
      substance in relation to convulsions induced by PTZ in mice. Pretreatment with N
      methyl-d-aspartate (NMDA) receptor antagonists (5S,10R)-(+)-5-methyl-10,11
      dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate (MK-801), (E)-(+/-)-2
      amino-4-methyl-5-phospho no-3-pentenoic acid ethyl ester, CGP39551) and DL-alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist
      (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide, NBQX)
      inhibited a subconvulsive dose of PTZ-induced convulsions in nNOS(-/-) mice,
      demonstrating that convulsions induced by PTZ are modulated by endogenous NO
      production and ionotropic glutamate receptor-mediated stimulation. These results
      suggest a negative or positive modulation of neuronal interactions by basal or
      enhanced NO production, respectively.

PMID- 19162140
TI  - Racemic intrathecal mirtazapine but not its enantiomers acts anti-neuropathic
      after chronic constriction injury in rats.
AB  - The unique noradrenergic and specific serotonergic antidepressant mirtazapine
      acts antinociceptive. It is optically active and currently marketed as racemate.
      In an animal model of acute pain it has been shown that the enantiomers exhibit
      differential effects: the R(-)-enantiomer showed anti-, the S(+)-enantiomer
      pronociceptive properties while the racemate acted antinociceptive at low doses
      and profoundly pronociceptive after high-dose application. Aim of the present
      study was to evaluate potential enantioselective effects of mirtazapine in
      neuropathic pain. In a chronic constriction injury model of neuropathic pain,
      Wistar rats were injected (+/-)-mirtazapine and the enantiomers intrathecally.
      All substances were dosed between 0.001 and 1mg/kg and compared to vehicle in a
      randomized and blinded approach. Thermal hyperalgesia and mechanical allodynia
      were assessed. In contrast to the acute pain results, only racemic mirtazapine
      exerted significant sustained analgesic effects up to 48 h. Antinociception was
      observed at all dosages with a maximum in the range of 0.01 mg/kg. Surprisingly,
      neither enantiomer was pro- nor antinociceptive at any dose or time. Our findings
      suggest that the synergism of both enantiomers is required to evoke a significant
      analgesic effect for the treatment of neuropathic pain. Our study gained no
      evidence for the use of either R(-) nor S(+)-mirtazapine alone. Due to the unique
      characteristics of (+/-)-mirtazapine and its proven efficacy in acute pain our
      results suggest that racemic mirtazapine may be a particularly useful
      antidepressant in the adjunctive treatment of chronic neuropathic pain states and
      could provide additional benefit to current therapeutic options.

PMID- 19162138
TI  - Abnormal structure-function relationships in hereditary dystonia.
AB  - Primary torsion dystonia (PTD) is a chronic movement disorder manifested
      clinically by focal or generalized sustained muscle contractions, postures,
      and/or involuntary movements. The most common inherited form of PTD is associated
      with the DYT1 mutation on chromosome 9q34. A less frequent form is linked to the
      DYT6 locus on chromosome 8q21-22. Both forms are autosomal dominant with
      incomplete (approximately 30%) clinical penetrance. Extensive functional and
      microstructural imaging with positron emission tomography (PET) and diffusion
      tensor MRI (DTI) has been performed on manifesting and non-manifesting carriers
      of these mutations. The results are consistent with the view of PTD as a
      neurodevelopmental circuit disorder involving cortico-striatal-pallido
      thalamocortical (CSPTC) and related cerebellar-thalamo-cortical pathways. Studies
      of resting regional metabolism have revealed consistent abnormalities in PTD
      involving multiple interconnected elements of these circuits. In gene carriers,
      changes in specific subsets of these regions have been found to relate to
      genotype, phenotype, or both. For instance, genotypic abnormalities in striatal
      metabolic activity parallel previously reported reductions in local D(2) receptor
      availability. Likewise, we have identified a unique penetrance-related metabolic
      network characterized by increases in the pre-supplementary motor area (SMA) and
      parietal association areas, associated with relative reductions in the
      cerebellum, brainstem, and ventral thalamus. Interestingly, metabolic activity in
      the hypermetabolic areas has recently been found to be modified by the penetrance
      regulating D216H polymorphism. The DTI data raise the possibility that metabolic
      abnormalities in mutation carriers reflect adaptive responses to developmental
      abnormalities in the intrinsic connectivity of the motor pathways. Moreover,
      findings of increased motor activation responses in these subjects are compatible
      with the reductions in cortical inhibition that have been observed in this
      disorder. Future research will focus on clarifying the relationship of these
      changes to clinical penetrance in dystonia mutation carriers, and the
      reversibility of disease-related functional abnormalities by treatment.

PMID- 19162141
TI  - Short-term habituation of eye-movement responses induced by galvanic vestibular
      stimulation (GVS) in the alert guinea pig.
AB  - In a recent study, we showed that primary afferent neurons innervating all
      vestibular end organs were sensitive to galvanic vestibular stimulation (GVS) in
      guinea pigs. In order to determine the three-dimensional character of eye
      movements induced by GVS, changes in eye position were recorded using digital
      video oculography during delivery of bilateral GVS ranging in intensity between
      20 and 80 microA. Pulses were delivered in repetitive trains in order to also
      ascertain the involvement of vestibular habituation. At low intensities of GVS
      (up to 40 microA), maintained changes in eye position were induced toward the
      anode and away from the cathode. These eye movements were predominantly vertical
      with some horizontal eye movement and very little or no torsion. At higher
      intensities of GVS (>40 microA), horizontal nystagmus was initially observed, as
      well as an overall deviation of the beating field toward the anode. Nystagmus was
      found to habituate rapidly over successive presentations of GVS, whereas the
      tonic deviation of the eye remained consistent without any detectable
      habituation. The direction of eye movements induced by GVS was similar to that
      observed in humans during trans-mastoidal GVS, and the threshold differences
      between tonic and phasic components for GVS were also similar to previous human
      GVS studies. The observed habituation appears to be more specific to the phasic
      VOR component in quadrupedal animals such as guinea pigs, and this may reflect a
      considerable emphasis placed on otolithic stimulation in these animals during
      complex locomotor activities.

PMID- 19162142
TI  - Comparative cognition in context: a tribute to the contributions of Sara J.
      Shettleworth.

PMID- 19162143
TI  - Context effect in a temporal bisection task with the choice keys available during
      the sample.
AB  - In a symbolic matching to sample task, six pigeons learned to associate different
      sample durations with different comparison stimuli. On "Short" trials, choice of
      Red and Green keylight comparisons were reinforced following 3-s and 9-s samples,
      respectively; on "Long" trials, Blue and Yellow keylight comparisons were
      reinforced following 9-s and 27-s samples, respectively. In contrast with
      previous studies, the comparison keys were available during the samples. After
      the temporal discriminations were learned, new pairs of comparison keys were
      presented and the preference for each was assessed during 27-s samples. One pair
      in particular, Green and Blue, was critical because it tested the predictions of
      two timing models, Scalar Expectancy Theory (SET) and the Learning-to-Time (LeT)
      model. The results showed that preference for Green increased during the sample,
      a result consistent with LeT but not with SET. Other test results, however, were
      predicted by neither model.

PMID- 19162144
TI  - The OrcPI locus: genomic organization, expression pattern, and noncoding regions
      variability in Orchis italica (Orchidaceae) and related species.
AB  - OrcPI is a class B MADS-box gene of Orchis italica (Orchidaceae), homologous of
      the PISTILLATA/GLOBOSA gene isolated in Arabidopsis and Antirrhinum. Its role in
      determining petals and stamens is conserved in orchids, where it seems to be
      involved also in other functions, such as flower longevity and ovary development.
      The present study reports the genomic characterization of the OrcPI locus in O.
      italica including coding and noncoding regions (introns, 5'- and 3' untranslated
      regions, and putative promoter). Nucleotide polymorphism distribution confirmed
      that this gene is subjected to different evolutionary forces, phylogenetic and
      distance analyses demonstrated that OrcPI is a useful nuclear marker at low
      taxonomic level in orchids. The expression pattern analysis showed that OrcPI
      transcripts are present in all the floral structures, undetected in the
      vegetative tissues, and decreased in the natural senescent flower. Finally, micro
      RNAs putative target sites were identified within the OrcPI gene, conserved among
      orchids.

PMID- 19162145
TI  - Cucumber, melon, pumpkin, and squash: are rules of editing in flowering plants
      chloroplast genes so well known indeed?
AB  - The similarities and differences in the chloroplast genes editing patterns of
      four species from one family (and two genera), which is the first-ever attempt at
      comparison of such data in closely related species, is discussed. The effective
      use of the chloroplast genes editing patterns in evolutionary studies, especially
      in evaluating the kinship between closely related species, is thereby proved. The
      results indicate that differences in editing patterns between different genera
      (Cucumis and Cucurbita) exist, and some novel editing sites can be identified
      even now. However, surprising is the fact of finding editing in the codon for Arg
      (in flowering plants detected before only in Cuscuta reflexa chloroplast genome,
      Funk et al.,[Funk H.T., Berg S., Krupinska K., Maier U.G. and Krause K., 2007.
      Complete DNA sequences of the plastid genomes of two parasitic flowering plants
      species, Cuscuta reflexa and Cuscuta gronovi. BMC Plant Biol. 7:45, doi:
      10.1186/1471-2229-7-45.]), which was believed to have been lost during evolution
      before the emergence of angiosperms. In addition, the existence of silent editing
      in plant chloroplasts has been confirmed, and some probable reasons for its
      presence are pointed out herein.

PMID- 19162146
TI  - Development of nobiliside A loaded liposomal formulation using response surface
      methodology.
AB  - To reduce the hemolysis and toxicity of nobiliside A (Nob), liposomes were used
      as a carrier in this study. Response surface methodology (RSM) based on central
      composite rotatable design (CCRD) was applied for formulation optimization.
      Phosphatidyl choline (PC) proportion, cholesterol (CH) proportion, and
      lipids/drug ratio were selected as the independent variables while the
      encapsulation efficiency (EE) and hemolytic rate (HR) of the liposomes as the
      dependent variables. The results indicated CH proportion and lipids/drug ratio
      were the major contributing variables for EE and PC/CH ratio was the major
      contributing variables for HR. The optimum formulation of Nob liposomes, in which
      PC proportion of 2% (w/v), CH proportion of 0.9% (w/v), and lipids/drug ratio
      (w/w) of 40, had higher EE (>95%) and lower HR (<1% at the concentration of 80
      microg mL(-1)) with spherical shape and uniform sizes. The intravenous LD50
      increased to 9.5 mg kg(-1) compared to 4.1 mg kg(-1) of Nob solution. In
      conclusion, the liposome was a safety and effective carrier for intravenous Nob.

PMID- 19162147
TI  - Production and characterization of Hesperetin nanosuspensions for dermal
      delivery.
AB  - Nanosuspensions of Hesperetin were produced using four different stabilizers,
      Poloxamer 188, Inutec SP1, Tween 80 and Plantacare 2000, possessing different
      mechanisms of stabilisation. The nanosuspensions were characterized with regard
      to size (photon correlation spectroscopy (PCS), laser diffractometry (LD)) and
      charge (zeta potential measurements). A nanocrystal PCS size of about 300 nm was
      obtained after 30 homogenization cycles at 1500 bar with the stabilizers
      Poloxamer, Inutec and Plantacare. Tween was slightly less efficient to preserve
      the nanocrystal size directly after production (347 nm). The short-term stability
      was assessed by storage of the nanosuspensions at 4 degrees C, room temperature
      and 40 degrees C. As predicted from the zeta potential measurements, Inutec and
      Plantacare stabilized nanosuspensions were stable with no change in PCS diameter
      and LD diameter 99%. Slight increases in size were found for the Poloxamer and
      the Tween stabilized nanosuspensions, which is not considered to impair their use
      in dermal formulations.

PMID- 19162148
TI  - Innovative formulations for the delivery of levothyroxine to the skin.
AB  - The aim of this work was to realize innovative transdermal formulations
      containing sodium levothyroxine in view of topical administration. Permeation
      experiments were performed in vitro, using rabbit ear skin as barrier. At the end
      of the permeation experiments levothyroxine retained in the skin was extracted
      and quantified by HPLC. Formulations tested were microemulsions and transdermal
      films. Microemulsions containing isopropyl myristate and isobutanol were shown to
      be able to increase levothyroxine solubility by the inclusion in reverse
      micelles. However, the inclusion in reversed micelles reduced the drug release to
      a significant extent, and consequently skin retention, compared to aqueous
      solutions. When the microemulsion was included in the transdermal film, drug
      retention was increased, probably for the enhancer effect of its excipients. The
      transdermal film proposed in this work could be an interesting alternative to
      semisolid formulations for the ease of use and the control in the amount of
      active applied. Additional benefit can be obtained if the film is used in
      occlusive conditions.

PMID- 19162149
TI  - Characterization and mosquito repellent activity of citronella oil nanoemulsion.
AB  - Encapsulated citronella oil nanoemulsion prepared by high pressure homogenization
      at varying amounts of surfactant and glycerol, was studied in terms of the
      droplet size, stability, release characteristics and in vivo mosquito protection.
      Transparent nanoemulsion can be obtained at optimal concentration of 2.5%
      surfactant and 100% glycerol. Physical appearance and the stability of the
      emulsion were greatly improved through an addition of glycerol, owing to its co
      solvent and highly viscous property. The increasing emulsion droplet increased
      the oil retention. The release behavior could be attributed to the effect of
      droplet size and concentrations of surfactant and glycerol. By fitting to
      Higuchi's equation, an increase in glycerol and surfactant concentrations
      resulted in slow release of the oil. The release rate related well to the
      protection time where a decrease in release rate can prolong mosquito protection
      time.

PMID- 19162150
TI  - Electrically controlled release of salicylic acid from poly(p-phenylene
      vinylene)/polyacrylamide hydrogels.
AB  - The apparent diffusion coefficients, Dapp, and the release mechanisms of
      salicylic acid from salicylic acid-loaded polyacrylamide hydrogels, SA-loaded
      PAAM, and salicylic acid-doped poly(phenylene vinylene)/polyacrylamide hydrogels,
      SA-doped PPV/PAAM, were investigated. In the absence of an electric field, the
      diffusion of SA from the SA-doped PPV/PAAM is delayed in the first 3 h due to the
      ionic interaction between the anionic drug (SA anion) and the PPV. Beyond this
      period, SA is dissolved in and can diffuse into the buffer solution through the
      PAAM matrix. The Dapp of the SA-doped PPV/PAAM is higher than that of the SA
      loaded PAAM, and the former increases with increasing electric field strength due
      to combined mechanisms: the expansion of PPV chains inside the hydrogel; the
      reduction reaction under a negative potential driving the anionic SA through the
      PAAM matrix; and the expansion of the matrix pore. The Dapp of SA from the SA
      loaded PAAM and the SA-doped PPV/PAAM apparently obey the scaling behavior:
      Dapp/D0 = (drug size/pore size)m with the scaling exponent m equal to 0.50 at 0.1
      V for both SA-loaded PAAM and SA-doped PPV/PAAM. Thus, the presence of the
      conductive polymer and the applied electric field can be combined to control the
      drug release rate at an optimal desired level.

PMID- 19162151
TI  - Morphology and in vitro release kinetics of drug-loaded micelles based on well
      defined PMPC-b-PBMA copolymer.
AB  - Well-defined amphiphilic diblock copolymers with different poly(2
      methacryloyloxyethyl phosphorylcholine) (PMPC) content were successfully
      synthesized via RAFT polymerization technology. The structure of the copolymers
      was confirmed using GPC, 1H NMR and FTIR. The polymers have very low critical
      micelles concentration (6.32 x 10(-7) mol/L to 1.01 x 10(-6) mol/L), which
      indicates their high thermodynamic stability needed for intravenous injection.
      Blank and paclitaxel-loaded polymeric micelles were prepared from the PMPC-b-PBMA
      copolymers using self-emulsion/evaporation method. TEM analysis revealed a
      regular spherical shape, small diameter (less than 30 nm) and narrow size
      distribution of the micelles. The paclitaxel-loaded polymeric micelles had high
      loading content (above 13%). In vitro release kinetics of paclitaxel from the
      micelles was also investigated. Less than 30% of the paclitaxel was released
      within 320 h and the increase of the length of PMPC leads to slower release rate.

PMID- 19162152
TI  - Solid state evaluation of some thalidomide raw materials.
AB  - Thalidomide presents polymorphism and is a problematic drug due to its poor
      solubility and difficult tablet processability, which is the dosage form
      available in Brazil. In most cases, the pharmacopoeias specify do not address
      solid state characterization of drugs precisely. In this work, different
      thalidomide commercial samples were characterized by infrared spectroscopy,
      particle size analysis, scanning electron microscopy, and X-ray diffraction. In
      addition, the polymorphic forms were quantified for Rietveld analysis and their
      intrinsic dissolution rates were evaluated. The results demonstrated the market
      availability of different raw materials which lack of homogeneity due to
      differences related to crystalline constitution, crystal habit and intrinsic
      dissolution rate.

PMID- 19162153
TI  - Inhibitory effects of Agaricus blazei extracts on human myeloid leukemia cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Agaricus blazei has been used as an adjuvant in
      cancer chemotherapy and is found to inhibit the growth of various types of tumor
      cells. AIM OF THE STUDY: Our study has adopted a systematic and bioassay-guided
      approach to optimize the extraction of Agaricus blazei for anti-leukemic
      bioactive components. The tumor-selective growth inhibitory activity of the
      extracts on leukemic cell lines was evaluated in vitro and in vivo using tumor
      bearing nude mice. MATERIALS AND METHODS: Agaricus blazei extracts were prepared
      using different methods. MTT and tritiated thymidine incorporation assays were
      used to evaluate the in vitro anti-leukemic effects. The most potent extract was
      further investigated using NB-4 cells-bearing nude mice and mechanistic studies
      using DNA fragmentation assay and cell death detection ELISA. RESULTS: The
      JAB80E70 extract showed the most potent tumor-selective growth inhibitory
      activity against human leukemia NB-4 and K-562 cells. This is the first report of
      anti-leukemic activity of JAB80E70 in athymic nude mice bearing NB-4 cells. Using
      DNA fragmentation assays and cell death detection ELISA, JAB80E70 was found to
      induce apoptosis in NB-4 cells. However, the polysaccharide enriched fractions
      failed to show significant cytotoxicity on NB-4 cells in vitro. CONCLUSIONS: The
      JAB80E70 extract exhibited potent anti-leukemic effect in vitro and in vivo. The
      effect can be attributed, at least in part, to the induction of apoptosis.
      Besides, polysaccharides in Agaricus blazei may not possess direct anti-leukemic
      activity in vitro.

PMID- 19162154
TI  - Appraisal of scopolamine-induced antiamnesic effect in mice and in vitro
      antiacetylcholinesterase and antioxidant activities of some traditionally used
      Lamiaceae plants.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvia species and Melissa officinalis are used
      for their memory-enhancing effects in European folk medicine. Teucrium polium was
      reported to be used in Anatolia for memory-enhancement in a very old book written
      by an Ottoman herbalist-physician. AIM OF THE STUDY: Alzheimer's disease (AD) is
      a progressive neurological disorder mostly affecting the elder population.
      Currently, there is no cure for the treatment of severe type of AD. Therefore, in
      this study, the hydroalcoholic extracts of three traditionally used Lamiaceae
      species for memory-enhancement; Salvia triloba L., Melissa officinalis L., and
      Teucrium polium L., were assessed for their in vivo antiamnesic activity along
      with in vitro anticholinesterase and antioxidant activities. MATERIALS AND
      METHODS: Scopolamine-induced antiamnesic activity was determined in mice by
      passive avoidance test, while anticholinesterase effect was measured by
      spectrophotometric Ellman method at 0.25, 0.50, 1.0, and 2.0 mg ml(-1) and
      antioxidant activity was assessed by scavenging effect against 2,2
      diphenylpicrylhydrazyl (DPPH). Total phenol contents of the extracts were
      determined by Folin-Ciocalteau method. RESULTS: Salvia triloba was the most
      effective in antiamnesic experiment at 100, 200, and 400 mg kg(-1) doses having
      22.7, 57.1, and 71.4% of relative effects, respectively. Teucrium polium was also
      active dose-dependently, whereas Melissa officinalis was completely inactive. In
      the anticholinesterase assay, the extracts showed similar inhibitions against
      acetylcholinesterase and Teucrium polium had the highest inhibition (65.8% at 1.0
      mg ml(-1)). Concerning the antioxidant effect, all the extracts exerted the
      highest activity among all having IC50 values between 0.227 and 0.428 mg/ml.
      CONCLUSION: Our data suggest that Teucrium polium among the screened plants
      deserves to be examined further as a herbal alternative for AD treatment.

PMID- 19162155
TI  - Antiulcerogenic action of ethanolic extract of the resin from Virola surinamensis
      Warb. (Myristicaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Virola surinamensis (Myristicaceae), popularly
      known as "mucuiba", "ucuuba" or "ucuuba do igapo" is a large tree that grows
      abundantly in "Varzea" forest and on river banks in the Brazilian states of
      Amazonas and Tocantins. The resin obtained by cuts on the stem bark is a reputed
      folk remedy in its natural form for the treatment of ulcer, gastritis,
      inflammation and cancer. AIM OF THE STUDY: The present work evaluated the
      pharmacological activity of the resin obtained from bark of V. surinamensis as
      antiulcerogenic in experimental in vivo model in order to observe whether its
      traditional use is justified. MATERIALS AND METHODS: The preventive action of
      ethanolic extract of V. surinamensis was evaluated in experimental in vivo models
      in rodents that simulated this disease in human gastric mucosa. RESULTS: Oral
      administration of acidified ethanol solution produced severe hemorrhagic lesions
      in glandular mucosa with ulcerative lesion of 50+/-11.5mm. In animals pretreated
      with V. surinamensis (500 mg/kg, p.o.) a significant inhibition of mucosal injury
      of 2.40+/-0.56 mm (95% inhibition) was detected. The V. surinamensis, at the same
      dose, also reduced significantly (p<0.05) the formation of gastric lesions
      induced by indomethacin (39%), stress (45%) and by pylorus ligature in mice (31%)
      when compared to animals treated with vehicle. The extract from V. surinamensis
      exerts gastroprotective action only when this extract contacts gastric mucosa
      (oral route) with increased pH values and reduced H+ concentration of gastric
      contents. The ethanolic extract of V. surinamensis resin was analyzed by TLC and
      spectrometric methods (NMR and ES-MS) and the main constituent of this extract
      was epicatechin. CONCLUSIONS: We suggest that the epicatechin present in V.
      surinamensis resin may be among active principles responsible for the antiulcer
      activity shown by the tested resin but their used suggest carefulness because
      toxicological symptoms mentioned by population.

PMID- 19162156
TI  - Potentilla--a review of its phytochemical and pharmacological profile.
AB  - The genus Potentilla is a member of the family Rosaceae, subfamily Rosoideae,
      which is mainly distributed in temperate, arctic and Alpine zones of the Northern
      hemisphere. This genus has been known since ancient times for its curative
      properties. Extracts of the aerial and/or underground parts have been applied in
      traditional medicine for the treatment of inflammations, wounds, certain forms of
      cancer, infections due to bacteria, fungi and viruses, diarrhoea, diabetes
      mellitus and other ailments. This comprehensive review provides a botanical
      description of Potentilla species and their phytochemical constituents in the
      aerial and underground parts. In vitro and in vivo pharmacological studies are
      reviewed and discussed, focussing on antidiarrhoic, anti-ulcerogenic, anti
      neoplastic, antiviral and antimicrobial, antihyperglycemic, anti-inflammatory,
      spasmolytic, hepatoprotective and antioxidative activities of Potentilla species.
      Most of the pharmacological effects can be explained by the high amount of
      tannins and to a lesser extent by triterpenes, present in all plant parts.
      However, future efforts should concentrate more on in vitro and in vivo studies
      and also on clinical trials in order to confirm traditional wisdom in the light
      of a rational phytotherapy. Especially the efficacy of Potentilla erecta rhizome
      extracts in the treatment of colitis ulcerosa and of viral infections should be
      further substantiated in clinical studies.

PMID- 19162157
TI  - Anti-Helicobacter pylori activity of plants used in Mexican traditional medicine
      for gastrointestinal disorders.
AB  - AIM OF THE STUDY: Helicobacter pylori is the major etiological agent of chronic
      active gastritis and peptic ulcer disease and is linked to gastric carcinoma.
      Treatment to eradicate the bacteria failed in many cases, mainly due to
      antibiotic resistance, hence the necessity of developing better therapeutic
      regimens. Mexico has an enormous unexplored potential of medicinal plants. This
      work evaluates the in vitro anti-H. pylori activity of 53 plants used in Mexican
      traditional medicine for gastrointestinal disorders. MATERIALS AND METHODS: To
      test the in vitro antibacterial activity, agar dilution and broth dilution
      methods were used for aqueous and methanolic extracts, respectively. RESULTS:
      Aqueous extracts of Artemisia ludoviciana subsp. mexicana, Cuphea aequipetala,
      Ludwigia repens,and Mentha x piperita (MIC 125 to <250 microg/ml) as well as
      methanolic extracts of Persea americana, Annona cherimola, Guaiacum coulteri, and
      Moussonia deppeana (MIC <7.5 to 15.6 microg/ml) showed the highest inhibitory
      effect. CONCLUSIONS: The results contribute to understanding the mode of action
      of the studied medicinal plants and for detecting plants with high anti
      Helicobacter pylori activity.

PMID- 19162158
TI  - Anti-hyperglycemic effects and mechanism of Bidens pilosa water extract.
AB  - AIM OF STUDY: Bidens pilosa has traditionally been used as an anti-diabetic
      phytomedicine. However, its alleged benefits and mechanism remain elusive. This
      study aimed to evaluate the effect and action of Bidens pilosa water extract on
      type 2 diabetes. MATERIALS AND METHODS: A daily dose of Bidens pilosa water
      extract or glimepiride, a positive control, was given orally to C57BL/KsJ-db/db
      mice once or for 28 days. Levels of blood glucose, serum insulin, and
      glycosylated hemoglobulin A1C, glucose tolerance, and islet structure were used
      to evaluate its anti-diabetic effects in db/db mice. Rat pancreatic islets and
      streptozocin-treated mice were tested for insulin-releasing mechanism of Bidens
      pilosa water extract. RESULTS: A daily dose of Bidens pilosa water extract given
      once or for 28 days significantly decreased blood glucose levels and increased
      serum insulin levels in db/db mice. Besides, 28-day treatment with Bidens pilosa
      water extract significantly improved glucose tolerance, decreased HbA1C levels
      and protected islet structure in db/db mice. Mechanism study showed that Bidens
      pilosa water extract stimulated insulin secretion via pancreatic islets.
      CONCLUSIONS: Our results suggest that Bidens pilosa water extract ameliorates
      type 2 diabetes in db/db mice via regulation of insulin secretion and islet
      protection.

PMID- 19162159
TI  - Flower extract of Panax notoginseng attenuates lipopolysaccharide-induced
      inflammatory response via blocking of NF-kappaB signaling pathway in murine
      macrophages.
AB  - AIM OF THE STUDY: The root of Panax notoginseng (PN) is commonly used to treat
      chronic liver disease with its therapeutic abilities to stop haemorrhage in the
      circulation, while the PN flower (PN-F) is largely unknown in the biological
      activities on inflammation and mechanisms of its actions. In this study, the
      pharmacologic effects of PN-F methanol extract on inflammation were investigated
      to address potential therapeutic or toxic effects in LPS-stimulated mouse
      macrophage cells, RAW264.7 cells. MATERIALS AND METHODS: Production of NO, PGE2
      and pro-inflammatory cytokines (TNF-alpha and IL-1beta) in supernatant, the
      expression of iNOS, COX-2 and cytokines, the phosphorylation of MAPK molecules
      (ERK1/2, JNK and p38 MAPK), and the activation of NF-kappaB in PN-F extract were
      assayed in LPS-stimulated RAW264.7 cells. RESULTS: PN-F extract significantly
      inhibited the productions of NO, PGE2, TNF-alpha and IL-1beta on the LPS
      stimulated RAW264.7 cells. In addition, PN-F extract suppressed the mRNA and
      protein expressions of iNOS, COX-2, TNF-alpha and IL-1beta in LPS-stimulated
      RAW264.7 cells. The molecular mechanism of PN-F extract-mediated attenuation in
      RAW264.7 cells has close a relationship to suppressing the phosphorylation of
      MAPK molecules such as ERK1/2, JNK and p38 MAPK, and the translocation of NF
      kappaB p65 subunit into nuclear. CONCLUSION: These results indicate that PN-F
      extract inhibits LPS-induced inflammatory response via the blocking of NF-kappaB
      signaling pathway in macrophages, and demonstrated that PN-F extract possesses
      anti-inflammatory properties in vitro.

PMID- 19162161
TI  - Nitroxide radical TEMPO reduces ozone-induced chemokine IL-8 production in lung
      epithelial cells.
AB  - Exposure to high levels of ozone (O(3)) damages respiratory tract epithelial
      cells. This research evaluated the ability of TEMPO (2,2,6,6
      tetramethylpiperidine-N-oxyl), a stable nitroxide free radical, to decrease O(3)
      mediated injury to a respiratory tract-derived cell line (A549 cells) by
      monitoring in this cell system the interleukine-8 (IL-8) production. TEMPO
      reduced O(3)-induced IL-8 production in A549 cells, as evidenced by PCR analysis,
      Western blot and ELISA assays. This behaviour is explainable on the basis of the
      reactivity between TEMPO with O(3) and/or O(3)-derived free radicals in
      biological systems. The study provides evidence that TEMPO reacts with O(3)
      and/or its cytotoxic products and may provide protections against O(3)-induced
      biotoxicities.

PMID- 19162160
TI  - Transcript analysis of nrrF, a Fur repressed sRNA of Neisseria gonorrhoeae.
AB  - Like most microorganisms, Neisseria gonorrhoeae alters gene expression in
      response to iron availability. The ferric uptake regulator Fur has been shown to
      be involved in controlling this response, but the extent of this involvement
      remains unknown. It is known that in addition to working directly to repress gene
      expression, Fur may also work indirectly by controlling additional regulatory
      elements. Using in silico analysis, we identified a putative small RNA (sRNA)
      homolog of the meningococcal nrrF locus, and demonstrate that this sRNA is iron
      repressible, suggesting that this is the gonococcal analog of the rhyB locus in
      Escherichia coli. Quantitative real-time RT-PCR analysis indicates that this
      transcript may also be temporally regulated. Transcript analysis identified the
      5' start of the transcript, using a single reaction, fluorescent-based, primer
      extension assay. This protocol allows for the rapid identification of
      transcriptional start sites of RNA transcripts, and could be used for high
      throughput transcript mapping.

PMID- 19162162
TI  - The alpha-like scorpion toxin BmK I enhances membrane excitability via persistent
      sodium current by preventing slow inactivation and deactivation of rNav1.2a
      expressed in Xenopus Oocytes.
AB  - BmK I is classified as alpha-like scorpion toxin that specifically binds the
      voltage-gated sodium channels via receptor site-3. Previous results showed BmK I
      induced epileptiform responses in rats via intra-hippocampal injection, but the
      mechanism has yet to be clarified. In this study, using two-electrode
      voltage/current clamp technique, we determined the effects of BmK I on rNav1.2a
      expressed in Xenopus oocytes. The results showed that BmK I prevented the
      development of slow inactivation of rNav1.2a from the open-state and enhanced the
      persistent sodium current (I(NaP)) at suprathreshold potentials in concentration
      dependence, whereas it hardly affected the fast inactivation. BmK I was also able
      to augment the subthreshold I(NaP) at high concentrations (>100nM) with
      disruption of the open-state deactivation. The increased I(NaP) accelerated the
      firing frequency in the oocytes that fired repetitively after electrode
      punctures, as well as raised the baseline potential and induced bursting of
      spikes in the quiescent oocytes. These results demonstrated that BmK I could
      target rNav1.2a and induce the I(NaP) by preventing the development of slow
      inactivation and deactivation from the open-state, leading to the enhancement of
      membrane excitability, which may be involved in the BmK I-induced epilepsy.

PMID- 19162163
TI  - Effects of selected endocrine disruptors on meiotic maturation, cumulus
      expansion, synthesis of hyaluronan and progesterone by porcine oocyte-cumulus
      complexes.
AB  - In most mammals, before ovulation, cumulus cells synthesize a large amount of
      hyaluronan (HA) that is organized into an extracellular matrix (ECM), which
      provides an essential microenvironment for in vivo oocyte fertilization. This
      process is called cumulus expansion. The present study assessed effects of
      selected endocrine disruptors (bisphenol A, BPA; 4-chloro-3-methyl phenol, CMP;
      di(2-ethylhexyl) phthalate, DEHP; and benzyl butyl phthalate, BBP) in a range of
      100pM-100microM, on follicle-stimulating hormone (FSH)-induced meiotic maturation
      and cumulus expansion of porcine oocyte-cumulus complexes (OCC) cultured in
      vitro. Moreover, FSH-stimulated production of hyaluronic acid (HA) and
      progesterone by cumulus cells was measured. Both phenols, BPA and CMP
      (100microM), significantly affected meiotic maturation of oocytes. The number of
      oocytes that underwent germinal vesicle breakdown (GVBD) (78.7% and 72.4%,
      respectively) as well as the rate of oocytes that reached metaphase II stage
      (MII) (50% and 53.6%, respectively) after 44h culture were decreased compared to
      control (89.6% for GVBD and 81.5% for MII). FSH-stimulated expansion of cumulus
      was altered by the highest concentration of BPA and CMP (70% and 64%,
      respectively vs. 80.3% in control). Although BPA did not alter FSH-stimulated HA
      synthesis by cumulus cells, its incorporation within the complex was reduced to a
      half of control value. Progesterone production by OCC was significantly changed
      in the presence of BPA or DEHP. Finally, our results provide valuable information
      that oocyte meiotic progression was adversely affected during in vitro culture
      with endocrine disruptors.

PMID- 19162164
TI  - Guanosine and synthetic organoselenium compounds modulate methylmercury-induced
      oxidative stress in rat brain cortical slices: involvement of oxidative stress
      and glutamatergic system.
AB  - Excessive formation of reactive oxygen species (ROS) and disruption of glutamate
      uptake have been pointed as two key mechanisms in methylmercury-toxicity. Thus,
      here we investigate the involvement of glutamatergic system in methylmercury
      (MeHg) neurotoxicity and whether diphenyl diselenide, ebselen and guanosine could
      protect cortical rat brain slices from MeHg-induced ROS generation. MeHg (100 and
      200 microM) increased 2',7'-dichlorodihydrofluorescin (DCFH) oxidation after 2h
      of exposure. At 50 microM, MeHg increased DCFH oxidation only after 5h of
      exposure. Guanosine (1 and 5 microM) did not caused any effect per se; however,
      it blocked the increase in DCFH caused by 200 or 50 microM MeHg. Ebselen (5 and
      10 microM) decreased significantly the DCFH oxidation after 2 and 5h of exposure
      to MeHg. Diphenyl diselenide (5 microM) did not change the basal DCFH oxidation,
      but abolished the pro-oxidant effect of MeHg. MK-801 also abolished the pro
      oxidant effect of MeHg. These results demonstrate for the first time the
      potential antioxidant properties of organoseleniun compounds and guanosine
      against MeHg-induced ROS generation after short-term exposure in a simple in
      vitro model. In conclusion, endogenous purine (guanosine) and two synthetic
      organoselenium compounds can modulate the pro-oxidant effect of MeHg in cortical
      brain slices.

PMID- 19162165
TI  - Quantitative structure-property relationship modeling of skin sensitization: a
      quantitative prediction.
AB  - A quantitative structure-property relationship (QSPR) model for predicting the
      skin sensitization effects of chemical compounds has been developed. An extensive
      database of test results from three exclusive test procedures was used for QSPR
      model development. Since the experimental procedure and end-point ranking of data
      for local lymph node assay (LLNA), guinea pig maximization test (GPMT), and
      Federal Institute for Health Protection of Consumers and Veterinary Medicine
      (BgVV) are different, three separate QSPR models were developed. Effective non
      linear regression models were used for QSPR model development. The predictive
      capability of the final QSPR models was further improved by using a combination
      of literature-recommended and structural descriptors. The resultant QSPR models
      are capable of predicting skin sensitization of the diverse set of molecules
      considered with accuracies of 90%, 95%, and 90% for the LLNA, GPMT, and BgVV
      datasets, respectively.

PMID- 19162166
TI  - Changes in the peripheral blood transcriptome associated with occupational
      benzene exposure identified by cross-comparison on two microarray platforms.
AB  - Benzene is an established cause of leukemia, and possibly lymphoma, in humans,
      but the underlying molecular pathways remain largely undetermined. We used two
      microarray platforms to identify global gene expression changes associated with
      well-characterized occupational benzene exposure in the peripheral blood
      mononuclear cells (PBMC) of a population of shoe-factory workers. Differential
      expression of 2692 genes (Affymetrix) and 1828 genes (Illumina) was found and the
      concordance was 50% (based on an average fold-change > or =1.3 from the two
      platforms), with similar expression ratios among the concordant genes. Four genes
      (CXCL16, ZNF331, JUN and PF4), which we previously identified by microarray and
      confirmed by real-time PCR, were among the top 100 genes identified by both
      platforms in the current study. Gene ontology analysis showed overrepresentation
      of genes involved in apoptosis among the concordant genes while pathway analysis
      identified pathways related to lipid metabolism. The two-platform approach allows
      for robust changes in the PBMC transcriptome of benzene-exposed individuals to be
      identified.

PMID- 19162167
TI  - Is there still a need for candidate gene approaches in the era of genome-wide
      association studies?
AB  - Most genetic variants associated with complex diseases in humans are believed to
      have a small impact on risk. With traditional candidate gene/pathway approaches
      several associations with disease risk could be identified. However, now that
      genome-wide association studies are feasible, the question arises if there is
      still a need for these approaches. By using HapMap data, we evaluated to which
      extent commercially available microarrays cover, through linkage disequilibrium,
      all currently known genes and biological processes in different populations.
      Furthermore, we estimated the power to detect an association with any specific
      SNP. Our study shows that coverage of individual genes and pathways by current
      commercial genotyping platforms is satisfactory for the vast majority of RefSeq
      gene regions. However, depending on the gene or the population, there may still
      be a need for candidate gene approaches, especially when looking at polymorphisms
      with low allele frequencies.

PMID- 19162168
TI  - Gender, race/ethnicity, personality, and interleukin-6 in urban primary care
      patients.
AB  - Gender, race/ethnicity, and personality are markers of significant psychosocial
      and biological variability. Each may have implications for allostatic load and
      resulting inflammatory processes, yet findings have been largely mixed. We
      investigated whether women, minorities, and those higher in Neuroticism and lower
      in Extraversion were at risk for elevated circulating levels of the pro
      inflammatory cytokine interleukin (IL)-6 in a sample of 103 middle aged and older
      urban primary care patients. Regression analyses controlling for age, education,
      current depression levels, and chronic medical conditions revealed that women,
      minorities, and individuals lower in Extraversion had higher circulating levels
      of IL-6. Analyses of more specific personality traits revealed that the
      sociability and positive emotions components of Extraversion were unassociated
      with IL-6, but the activity facet-reflecting dispositional vigor and energy-was
      robustly associated with IL-6. The difference between high (+1 Standard Deviation
      (SD)) and low (-1 SD) trait activity was sufficient to shift IL-6 levels beyond a
      previously established high risk cut-point in both white and minority women.
      These findings suggest that while broad group differences between genders and
      races/ethnicities exist, personality represents an important source of individual
      differences in inflammation within groups. Future work should examine to what
      extent IL-6 levels are linked to temperament or genetic activity levels vs.
      physical activity itself, and whether IL-6 levels may be reduced by boosting
      regular activity levels in demographic segments such as women and minorities who
      appear susceptible to greater inflammation.

PMID- 19162169
TI  - Gender differences in delayed-type hypersensitivity response: effects of stress
      and coping in first-year law students.
AB  - Law students show significant deficits in emotional and physical well-being
      compared with groups of students in other areas of higher education. Furthermore,
      evidence suggests that these effects may be worse for women than for men. The use
      of active coping can positively affect immunity under stress, but this may be
      most true for men in the context of law school. The current study examined the
      delayed-type hypersensitivity (DTH) skin responses of first-year law students
      (n=121) and a comparison group (n=30). Students' health behaviors, self
      evaluative emotions, and coping strategies were also reported. Male law students
      had larger DTH responses than females, but this gender effect was not present in
      the comparison group. Endorsement of perseverance under stress (n=19), an active
      coping strategy, moderated the gender effect on immunity. Perseverance associated
      with larger DTH responses and more positive self-evaluative emotion, but only
      among men. These results indicate that active coping may be less efficacious for
      women than for men in law school, which in turn may limit women's opportunities
      to attenuate negative effects of law school.

PMID- 19162170
TI  - Early gene expression changes during embryonic stem cell differentiation into
      cardiomyocytes and their modulation by monobutyl phthalate.
AB  - The Embryonic Stem cell Test (EST) is an in vitro alternative test designed for
      the prediction of embryotoxicity. The endpoint of the test is the interference
      with mesoderm-derived cardiac muscle differentiation observed under the
      microscope as beating muscle foci. The relative subjectivity of this endpoint, as
      well as the applicability domain and related predictivity need further to be
      defined to facilitate implementation of the EST into regulatory strategies. The
      use of transcriptomics techniques to monitor differentiation-related gene
      expression changes in the EST might improve the EST in each of these aspects.
      Therefore, we studied the gene expression profile in embryonic stem cells (ESC)
      in the early phase of differentiation and its modulation by exposure to the well
      known embryotoxicant monobutyl phthalate (MBP). Cells were exposed from the early
      embryoid body stage onwards and RNA was collected after 6, 12 and 24h of
      exposure. Samples were hybridized to spotted microarrays, containing 21,997-mer
      oligonucleotides. Differential gene expression patterns were analyzed. A total
      number of 43 genes that were found to be upregulated in this study as a
      consequence of induction of cardiomyocyte differentiation were combined in a gene
      set, named 'VAN_DARTEL_HEARTDIFF_24H'. Gene Set Enrichment Analysis (GSEA)
      comparative analysis using multiple gene set collections clearly showed that
      temporal changes in gene expression were functionally related to cardiomyocyte
      differentiation. Furthermore, exposure of embryoid bodies (EB) to MBP increased
      expression of pluripotency-, proliferation- and nonmesodermal differentiation
      related gene sets, which indicates inhibition of mesodermal differentiation. The
      inhibition of mesoderm-derived cardiomyocyte differentiation by MBP exposure was
      most obvious through the downregulation of our novel gene set identified in this
      study, 'VAN_DARTEL_HEARTDIFF_24H', which specifically describes the niche of
      early cardiomyocyte differentiation. The gene set defined in this study might
      serve as a starting point for defining a dedicated gene set for early detection
      of embryotoxicity in the EST. Such a gene set may serve as an improved endpoint
      in the EST as compared to morphology, and will allow a more detailed definition
      of the applicability domain and predictivity of EST.

PMID- 19162171
TI  - Pregnancy outcome of women inadvertently exposed to ribostamycin during early
      pregnancy: a prospective cohort study.
AB  - No information is currently available on the safety of the aminoglycoside
      ribostamycin in pregnancy. We aimed to study the pregnancy outcome of women
      inadvertently exposed to ribostamycin during the first trimester of pregnancy. In
      a prospective cohort study, 102 women inadvertently exposed to ribostamycin
      during the first trimester of pregnancy and an age- and gravidity-matched control
      group, were enrolled. Study outcomes were gestational age at birth, major and
      minor malformations, and birth weight. Fetal outcomes were evaluated in 85 women
      inadvertently exposed to ribostamycin during the first-trimester of pregnancy and
      in 170 control subjects. Newborns were clinically examined at birth by a
      neonatologist and by imaging studies if any suspicious abnormalities were noted.
      There were 4/85 (4.9%) babies born with major malformations in the exposed group
      and 3/170 (1.8%) in the control group (P=0.7). Gestational age at delivery, rate
      of minor anomalies, rate of preterm births, and birth weight were not different
      between groups. In conclusion, similar to what is reported for other
      aminoglycoside, exposure to ribostamycin during the first-trimester of pregnancy
      does not appear to increase the risk of adverse fetal outcomes.

PMID- 19162172
TI  - Gestational and lactational exposure to potassium perfluorooctanesulfonate
      (K+PFOS) in rats: developmental neurotoxicity.
AB  - Perfluorooctanesulfonate (PFOS), a persistent and bioaccumulative compound, is
      widely distributed in humans and wildlife. Exposure of the human fetus and
      neonate to PFOS can occur in utero and via the mother's milk, respectively.
      Developmental studies have been conducted with PFOS in the past, including some
      developmental neurotoxicity endpoints. The objective of this study was to
      evaluate the functional and morphological changes to the nervous system in rats
      having gestational and lactational exposures to PFOS per current test guidelines
      (EPA OPPTS 870.6300 and OECD 426). Female SD rats (25/dosage group) were given
      daily oral doses of either 0.0, 0.1, 0.3, or 1.0mg/kg-d potassium PFOS (K(+)PFOS)
      from gestation day (GD) 0 through postnatal day (PND) 20. Offspring were observed
      through PND 72 for growth, maturation, motor activity, learning and memory,
      acoustic startle reflex, various behavioral manifestations, and brain weight.
      Specimens were taken from dams, fetuses, and pups for serum and tissue PFOS
      concentration, thyroid status endpoints, and liver mRNA transcript analysis, and
      those results are reported in a companion article. No significant effect was
      noted on maternal health or reproductive outcomes from dosing of maternal rats
      with K(+)PFOS throughout gestation. Maternal body weights were statistically
      significantly lower in the 1.0mg/kg-d dosage group from PND 4 through the end of
      lactation. Offspring from K(+)PFOS-treated maternal groups did not differ
      significantly from controls with respect to birth weight, growth, age and weight
      at attainment of sexual maturation, learning and memory, acoustic startle,
      various behavioral endpoints, and brain weight. Male offspring from the 1.0mg/kg
      d maternal treatment group displayed increased motor activity and reduced
      habituation on PND 17 but not on PND 13, 21, and 61. The maternal no-observed
      adverse-effect-level (NOAEL) was 0.3mg/kg-d based on decreased body weights
      observed in lactation. The maternal dose associated with the NOAEL for male
      offspring was 0.3mg/kg-d based on increased motor activity and reduced
      habituation in the 1.0mg/kg-d maternal dose-group male offspring on PND 17. The
      maternal dose associated with the NOAEL for female offspring was >1.0mg/kg-d.
      Mean serum concentrations of PFOS reported in a companion article for the
      0.3mg/kg-d group maternal rats are several hundred times higher than those
      reported for females in the United States general population.

PMID- 19162173
TI  - Evidence for the involvement of xenobiotic-responsive nuclear receptors in
      transcriptional effects upon perfluoroalkyl acid exposure in diverse species.
AB  - Humans and ecological species have been found to have detectable body burdens of
      a number of perfluorinated alkyl acids (PFAA) including perfluorooctanoic acid
      (PFOA) and perfluorooctane sulfonate (PFOS). In mouse and rat liver these
      compounds elicit transcriptional and phenotypic effects similar to peroxisome
      proliferator chemicals (PPC) that work through the nuclear receptor peroxisome
      proliferator-activated receptor alpha (PPAR alpha). Recent studies indicate that
      along with PPAR alpha other nuclear receptors are required for transcriptional
      changes in the mouse liver after PFOA exposure including the constitutive
      activated receptor (CAR) and pregnane X receptor (PXR) that regulate xenobiotic
      metabolizing enzymes (XME). To determine the potential role of CAR/PXR in
      mediating effects of PFAAs in rat liver, we performed a meta-analysis of
      transcript profiles from published studies in which rats were exposed to PFOA or
      PFOS. We compared the profiles to those produced by exposure to prototypical
      activators of CAR, (phenobarbital (PB)), PXR (pregnenolone 16 alpha-carbonitrile
      (PCN)), or PPAR alpha (WY-14,643 (WY)). As expected, PFOA and PFOS elicited
      transcript profile signatures that included many known PPAR alpha target genes.
      Numerous XME genes were also altered by PFOA and PFOS but not WY. These genes
      exhibited expression changes shared with PB or PCN. Reexamination of the
      transcript profiles from the livers of chicken or fish exposed to PFAAs indicated
      that PPAR alpha, CAR, and PXR orthologs were not activated. Our results indicate
      that PFAAs under these experimental conditions activate PPAR alpha, CAR, and PXR
      in rats but not chicken and fish. Lastly, we discuss evidence that human
      populations with greater CAR expression have lower body burdens of PFAAs.

PMID- 19162174
TI  - A novel hybridization approach for detection of citrus viroids.
AB  - Citrus plants are natural hosts of several viroid species all belonging to the
      family Pospiviroidae. Previous attempts to detect viroids from field-grown
      species and cultivars yielded erratic results unless analyses were performed
      using Etrog citron a secondary bio-amplification host. To overcome the use of
      Etrog citron a number of RT-PCR approaches have been proposed with different
      degrees of success. Here we report the suitability of an easy to handle northern
      hybridization protocol for viroid detection of samples collected from field-grown
      citrus species and cultivars. The protocol involves: (i) Nucleic acid
      preparations from bark tissue samples collected from field-grown trees regardless
      of the growing season and storage conditions; (ii) Separation in 5% PAGE or 1%
      agarose, blotting to membrane and fixing; (iii) Hybridization with viroid
      specific DIG-labelled probes and detection with anti-DIG-alkaline phosphatase
      conjugate and autoradiography with the CSPD substrate. The method has been tested
      with viroid-infected trees of sweet orange, lemon, mandarin, grapefruit, sour
      orange, Swingle citrumello, Tahiti lime and Mexican lime. This novel
      hybridization approach is extremely sensitive, easy to handle and shortens the
      time needed for reliable viroid indexing tests. The suitability of PCR generated
      DIG-labelled probes and the sensitivity achieved when the samples are separated
      and blotted from non-denaturing gels are discussed.

PMID- 19162175
TI  - Feasibility of single nucleotide polymorphism genotyping with a single-probe by
      time-resolved Forster resonance energy transfer.
AB  - By tens-of-picosecond resolved fluorescence detection we study Forster resonance
      energy transfer between a donor and a black-hole-quencher acceptor bound at the
      5'- and 3'-positions of a synthetic DNA oligonucleotide. This dual-labelled
      oligonucleotide is annealed with either the complementary sequence or with
      sequences differing in one nucleotide at positions near either the ends or the
      centre of the oligonucleotide. We find donor fluorescence decay times whose
      values are definitely distinct and discuss the feasibility of single nucleotide
      polymorphism genotyping by this method.

PMID- 19162176
TI  - A novel growth hormone 1 gene-derived probe for Oncorhynchus masou formosanus
      distinguished from the Oncorhynchus subspecies.
AB  - Traditional mitochondrial 16S rRNA is commonly used in many species
      identification studies. However, it is difficult to apply to the phylogenetic
      studies among the Oncorhynchus subspecies, which is a crucial need for management
      purposes for Oncorhynchus masou formosanus, Taiwan salmon. In this study, we have
      developed an improved species identification method for Taiwan salmon
      distinguished with other Oncorhynchus subspecies tested by exploiting PCR for
      growth hormone (GH) 1 gene. By comparing DNA sequences for GH1 from 11 species of
      Oncorhynchus subspecies we designed novel PCR primers that exploit differences
      between Taiwan salmon and other Oncorhynchus subspecies. Therefore, the technique
      is an important tool in the management of populations of the endangered land
      locked Taiwan salmon preventing from their possible hybrids with other
      Oncorhynchus subspecies once tested.

PMID- 19162178
TI  - Membrane transport of WAVE2 and lamellipodia formation require Pak1 that mediates
      phosphorylation and recruitment of stathmin/Op18 to Pak1-WAVE2-kinesin complex.
AB  - Membrane transport of WAVE2 that leads to lamellipodia formation requires a small
      GTPase Rac1, the motor protein kinesin, and microtubules. Here we explore the
      possibility of whether the Rac1-dependent and kinesin-mediated WAVE2 transport
      along microtubules is regulated by a p21-activated kinase Pak as a downstream
      effector of Rac1. We find that Pak1 constitutively binds to WAVE2 and is
      transported with WAVE2 to the leading edge by stimulation with hepatocyte growth
      factor (HGF). Concomitantly, phosphorylation of tubulin-bound stathmin/Op18 at
      serine 25 (Ser25) and Ser38, microtubule growth, and stathmin/Op18 binding to
      kinesin-WAVE2 complex were induced. The HGF-induced WAVE2 transport, lamellipodia
      formation, stathmin/Op18 phosphorylation at Ser38 and binding to kinesin-WAVE2
      complex, but not stathmin/Op18 phosphorylation at Ser25 and microtubule growth,
      were abrogated by Pak1 inhibitor IPA-3 and Pak1 depletion with small interfering
      RNA (siRNA). Moreover, stathmin/Op18 depletion with siRNA caused significant
      inhibition of HGF-induced WAVE2 transport and lamellipodia formation, with HGF
      independent promotion of microtubule growth. Collectively, it is suggested that
      Pak1 plays a critical role in HGF-induced WAVE2 transport and lamellipodia
      formation by directing Pak1-WAVE2-kinesin complex toward the ends of growing
      microtubules through phosphorylation and recruitment of tubulin-bound
      stathmin/Op18 to the complex.

PMID- 19162179
TI  - Oxidative and nitrosative stress in Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder marked by
      movement impairment caused by a selective degeneration of dopaminergic neurons.
      The mechanism for dopaminergic neuronal degeneration in PD is not completely
      clear, but it is believed that oxidative and nitrosative stress plays an
      important role during the pathogenesis of PD. This notion is supported by various
      studies that several indices of oxidative and nitrosative stress are increased in
      PD patients. In recent years, different pathways that are known to be important
      for neuronal survival have been shown to be affected by oxidative and nitrosative
      stress. Apart from the well-known oxidative free radicals induced protein
      nitration, lipid peroxidation and DNA damage, increasing evidence also suggests
      that some neuroprotective pathways can be affected by nitric oxide through S
      nitrosylation. In addition, the selective dopaminergic neurodegeneration suggests
      that generation of oxidative stress associated with the metabolism of dopamine is
      an important contributor. Thorough understanding of how oxidative stress can
      contribute to the pathogenesis of PD will help formulate potential therapy for
      the treatment of this neurodegenerative disorder in the future.

PMID- 19162180
TI  - Emerging roles of desumoylating enzymes.
AB  - Posttranslational modification by small ubiquitin-like modifier (SUMO) controls
      diverse cellular processes including transcriptional regulation, nuclear
      transport, cell-cycle progression, DNA repair, and signal transduction pathway.
      Sumoylation is a highly dynamic process that is reversed by a family of
      Sentrin/SUMO-specific proteases (SENPs). Thus, desumoylation process must be
      important for regulation of the fate and function of SUMO-conjugated proteins as
      well as SUMOylation process. SENPs catalyze the removal of SUMO from SUMO
      conjugated target proteins as well as the cleavage of SUMO from its precursor
      proteins. Since the first report of yeast desumoylating enzymes, many studies
      have revealed the structural and cellular biological properties of SENP family.
      This review focuses on the specificity of the SENPs' catalytic activities with
      regard to SUMO isoforms and their emerging roles as cellular regulators.

PMID- 19162177
TI  - Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2.
AB  - Ascorbate (vitamin C) is a vital antioxidant molecule in the brain. However, it
      also has a number of other important functions, participating as a cofactor in
      several enzyme reactions, including catecholamine synthesis, collagen production,
      and regulation of HIF-1 alpha. Ascorbate is transported into the brain and
      neurons via the sodium-dependent vitamin C transporter 2 (SVCT2), which causes
      accumulation of ascorbate within cells against a concentration gradient.
      Dehydroascorbic acid, the oxidized form of ascorbate, is transported via glucose
      transporters of the GLUT family. Once in cells, it is rapidly reduced to
      ascorbate. The highest concentrations of ascorbate in the body are found in the
      brain and in neuroendocrine tissues such as adrenal, although the brain is the
      most difficult organ to deplete of ascorbate. Combined with regional asymmetry in
      ascorbate distribution within different brain areas, these facts suggest an
      important role for ascorbate in the brain. Ascorbate is proposed as a
      neuromodulator of glutamatergic, dopaminergic, cholinergic, and GABAergic
      transmission and related behaviors. Neurodegenerative diseases typically involve
      high levels of oxidative stress and thus ascorbate has been posited to have
      potential therapeutic roles against ischemic stroke, Alzheimer's disease,
      Parkinson's disease, and Huntington's disease.

PMID- 19162181
TI  - In vitro permeation of desmopressin across rabbit nasal mucosa from liquid nasal
      sprays: the enhancing effect of potassium sorbate.
AB  - Nasal spray products containing desmopressin acetate (DDAVP) were tested in vitro
      to evaluate the effect of the contained preservatives on drug permeation across
      rabbit nasal mucosa. Experiments were performed using Franz-type diffusion cells
      with rabbit nasal mucosa as model barrier. Transport profiles obtained in
      comparison with a preservative-free solution evidenced that in the presence of
      preservatives DDAVP permeation in vitro always increased (p<0.05), although at
      different extents (chlorobutanol<benzalkonium<sorbate). While for benzalkonium
      structural damage of the mucosa could occur decreasing its barrier properties,
      the effect of sorbate on drug transport was further investigated, being less
      studied. After having found that sorbate permeated together with DDAVP, the
      hypothesis that the two compounds formed an ion pair in solution with improved
      permeability was made. Additional experiments with aqueous test solutions
      reconstructed ad hoc containing desmopressin and varying sorbate concentrations
      confirmed the enhancing effect of sorbate, which however resulted to be
      independent of sorbate concentration. In conclusion, preservatives significantly
      enhanced desmopressin permeation in vitro across rabbit nasal mucosa with
      different mechanisms. If a correlation existed between these data and in vivo
      DDAVP bioavailability after nasal administration, this could strengthen the
      safety concerns related to the use of this medication in adults and children.

PMID- 19162182
TI  - Purification and characterization of a small cationic protein from the tobacco
      hornworm Manduca sexta.
AB  - The prophenoloxidase (proPO) activation system is an important defense mechanism
      in arthropods, and activation of proPO to active phenoloxidase (PO) involves a
      serine proteinase cascade. Here, we report the purification and characterization
      of a small cationic protein CP8 from the tobacco hornworm, Manduca sexta, which
      can stimulate proPO activation. BLAST search showed that Manduca CP8 is similar
      to a fungal proteinase inhibitor-1 (AmFPI-1), an inducible serine proteinase
      inhibitor-1 (ISPI-1), and other small cationic proteins with unknown functions.
      However, we showed that Manduca CP8 did not inhibit proteinase activity, but
      stimulated proPO activation in plasma. When small amount (0.1 microg) of purified
      native CP8 or BSA was added to cell-free plasma samples and incubated for 20 min,
      low PO activity was observed in both groups. But significantly higher PO activity
      was observed in the CP8-group than in the BSA-group when more proteins (0.5
      microg) were added and incubated for 20 min. However, when the plasma samples
      were incubated with proteins for 30 min, high PO activity was observed in both
      the CP8 and BSA groups regardless of the amount of proteins added. Moreover, when
      PO in the plasma was pre-activated with Micrococcus luteus, addition of CP8 did
      not have an effect on PO activity, and CP8/bacteria mixture did not stimulate PO
      activity to a higher level than did BSA/bacteria. These results suggest that CP8
      helps activate proPO more rapidly at the initial stage. CP8 mRNA was specifically
      expressed in fat body and its mRNA level decreased when larvae were injected with
      saline or bacteria. However, CP8 protein concentration in hemolymph did not
      change significantly in larvae injected with saline or microorganisms.

PMID- 19162183
TI  - Delayed onset CMV disease in solid organ transplant recipients.
AB  - It is estimated that three-quarters of all patients undergoing solid organ
      transplantation experience new infection or reactivation of latent
      cytomegalovirus (CMV). The adoption of universal antiviral prophylactic
      strategies among high risk patients has significantly reduced the incidence of
      CMV infection and disease over the first three months. However, depending on the
      type of transplant and the pretransplant donor-recipient CMV serostatus, up to
      30% of patients may develop disease after three months (late disease), or at any
      time later than 1-2 years following transplantation (very late disease). The
      occurrence of late and very late CMV, referred to here as delayed onset CMV,
      places patients at risk for malignancy, graft loss and mortality. Clinical
      management of delayed onset CMV disease may be complicated by the presentation of
      nonspecific or atypical symptoms. The potential for missed diagnoses may be
      compounded by the long term management of patients by healthcare professionals
      who do not practice transplantation as a primary specialty. The current clinical
      goal is to ensure excellent long term outcomes among transplant recipients.
      Therefore, the present review will discuss the natural history and risk factors,
      as well as the therapeutic strategies relevant to the occurrence and management
      of late and very late CMV disease following solid organ transplantation in
      adults.

PMID- 19162184
TI  - A novel method for monitoring glucocorticoid-induced changes of the
      glucocorticoid receptor in kidney transplant recipients.
AB  - INTRODUCTION: Initial high dose glucocorticosteroid (GC) treatment of transplant
      recipients induces changes in the glucocorticoid receptor (GR) that may affect
      the mode of action of the drug. We developed a TaqMan one-step RT-PCR
      quantification method to investigate the effect of bolus GC treatment on the
      structure of the GR complex by measuring the levels of GR isoform expression and
      FK binding protein 5 (FKBP5) transcription. METHODS: Peripheral blood mononuclear
      cells (PBMCs) were obtained before renal transplantation and immediately after
      the initial methylprednisolone treatment. Gene expression of the GR-alpha, -beta,
      -P isoforms and FKBP5 were quantified using a simplex TaqMan relative
      quantification assay. Genotyping was performed using the TaqMan allele
      discrimination assay. RESULTS: The gene expression assay was validated and is
      efficient to detect extremely low quantity of GR-beta expression. Increased
      expression of FKBP5 (14.01+11.52 folds), GR-alpha (1.47+1.00 folds), GR-beta
      (6.21+5.71 folds) and GR-P (2.72+1.90 folds) were observed after steroid bolus.
      The GR haplotype A-T-G is significantly related to elevation of GRbeta
      transcription (p=0.002). Patients' hospitalization time after transplantation
      correlated with increment of GR-alpha (p=0.01) and FKBP5 (p=0.007) gene
      expression. The GR-beta expression level is extremely low compared with the GR
      alpha isoform. By contrast, the GR-P isoform is relatively abundantly expressed
      in PBMCs. CONCLUSION: The method to measure GR isoform enabled us to determine
      that acute high-dose GC treatment alters the structure of the GR. The initial
      therapy with high dose steroid may induce a GC resistance phenotype. The
      modulatory role of the GR-P isoform is not fully defined but may provide another
      dimension in understanding the function of GR and the role of steroid in
      transplant immunosuppression.

PMID- 19162186
TI  - Cortical PIB binding in Lewy body disease is associated with Alzheimer-like
      characteristics.
AB  - About one fourth of Lewy body disease (LBD) patients show cortical beta-amyloid
      load, basically a hallmark of Alzheimer disease (AD). Using [11C]PIB-PET, we
      tested whether LBD patients with beta-amyloid burden differ from those without
      with respect to demographic, clinical, biochemical and genetic parameters. Thirty
      five LBD subjects (9 patients with Lewy body dementia, DLB; 12 demented Parkinson
      patients, PDD; 14 non-demented PD, PDND) underwent [11C]PIB-PET, and were
      classified as either PIB(+) or PIB(-) according to cortical PIB uptake. PIB+ and
      PIB(-) patients were then compared according to demographic, clinical,
      biochemical and genetic parameters. None of the PDND, but four PDD and four DLB
      subjects were PIB+. In PIB+ subjects, ApoE4 prevalence was higher, CSF Abeta42
      levels were lower and, among demented patients, PIB-binding was associated with a
      lower MMSE score. Motor symptoms were not associated with PIB binding. Thus, LBD
      patients with cortical beta-amyloid show characteristics usually observed in AD.

PMID- 19162187
TI  - delta-Aminolevulinate dehydratase activity and oxidative stress during melphalan
      and cyclophosphamide-BCNU-etoposide (CBV) conditioning regimens in autologous
      bone marrow transplantation patients.
AB  - Severe toxicity is associated with cytotoxic drugs used during the conditioning
      regimen (CR) preceding bone marrow transplantation (BMT). The aim of this study
      was to evaluate the involvement of oxidative stress and possible use of delta
      aminolevulinate dehydratase (delta-ALA-D) activity as a marker of oxidative
      stress in autologous BMT patients. We have also compared common drugs that are
      used during CR, namely, melphalan (M-200) and cyclophosphamide-BCNU-etoposide
      (CBV), in order to determine whether either of them could be less toxic to
      patients in terms of oxidative stress. The sample consisted of 10 patients
      admitted for autologous BMT, 5 with M-200 CR and 5 with CBV CR and 10 healthy
      controls. Lipid peroxidation (estimated as thiobarbituric acid-reactive
      substances, TBARS), vitamin C, thiol levels, catalase, superoxide dismutase and
      delta-ALA-D activity were determined before CR, during CR and on days 10 and 20
      after BMT. Signs of exacerbated oxidative stress were minimal before CR, except
      for the CVB group (patients with lymphoma) where an increase in TBARS and a
      decrease in P-SH were detected. Indices of oxidative stress changed in both
      groups (CBV and M-200) during CR and up to 20 days after BMT. There was a
      decrease in enzymatic and non-enzymatic antioxidant defenses and in delta-ALA-D
      activity and an increase in lipoperoxidation in the blood of both patient groups.
      In conclusion, CBV and, principally, M-200 caused oxidative stress in patients
      undergoing autologous BMT and blood delta-ALA-D activity seems to be an
      additional biomarker of oxidative stress in BMT patients.

PMID- 19162188
TI  - Plasma homovanillic acid and family history of psychotic disorders in bipolar I
      patients.
AB  - It has been suggested that the family history of psychotic disorders is useful in
      defining homogeneous groups of bipolar patients. The plasma homovanillic acid
      (pHVA) concentrations have been related to the effect of antipsychotic treatment
      in psychotic patients. We have studied the influence of a positive family history
      of psychotic disorders both on the variation of pHVA levels and on the relation
      between pHVA concentrations and the clinical response to treatment. Clinical
      status and pHVA levels were assessed in 58 medication free patients before and
      after 4 weeks of treatment with olanzapine and lithium. Clinical improvement
      correlated positively with pHVA levels on the 28th day of treatment only in the
      patients having first degree relatives with psychotic disorders. The pHVA levels
      did not decrease after 28 days of treatment. Our results reinforce the idea that
      a positive family history of psychosis in psychotic bipolar disorders may
      constitute a good basis for sub-grouping these patients.

PMID- 19162185
TI  - Expression of inflammatory genes induced by beta-amyloid peptides in human brain
      endothelial cells and in Alzheimer's brain is mediated by the JNK-AP1 signaling
      pathway.
AB  - Alzheimer's disease (AD) is characterized by accumulation and deposition of Abeta
      peptides in the brain. Abeta deposition in cerebral vessels occurs in many AD
      patients and results in cerebral amyloid angiopathy (AD/CAA). Abeta deposits
      evoke neuro- and neurovascular inflammation contributing to neurodegeneration. In
      this study, we found that exposure of cultured human brain endothelial cells
      (HBEC) to Abeta(1-40) elicited expression of inflammatory genes MCP-1, GRO, IL
      1beta and IL-6. Up-regulation of these genes was confirmed in AD and AD/CAA
      brains by qRT-PCR. Profiling of 54 transcription factors indicated that AP-1 was
      strongly activated not only in Abeta-treated HBEC but also in AD and AD/CAA
      brains. AP-1 complex in nuclear extracts from Abeta-treated HBEC bound to AP-1
      DNA-binding sequence and activated the reporter gene of a luciferase vector
      carrying AP-1-binding site from human MCP-1 gene. AP-1 is a dimeric protein
      complex and supershift assay identified c-Jun as a component of the activated AP
      1 complex. Western blot analyses showed that c-Jun was activated via JNK-mediated
      phosphorylation, suggesting that as a result of c-Jun phosphorylation, AP-1 was
      activated and thus up-regulated MCP-1 expression. A JNK inhibitor SP600125
      strongly inhibited Abeta-induced c-Jun phosphorylation, AP-1 activation, AP-1
      reporter gene activity and MCP-1 expression in cells stimulated with Abeta
      peptides. The results suggested that JNK-AP1 signaling pathway is responsible for
      Abeta-induced neuroinflammation in HBEC and Alzheimer's brain and that this
      signaling pathway may serve as a therapeutic target for relieving Abeta-induced
      inflammation.

PMID- 19162189
TI  - Donor pre-treatment with tacrolimus reduces transplant vasculopathy.
AB  - We tested whether transplant arteriosclerosis can be reduced by pre-treatment of
      the donor with immunosuppressive agents, using a rat allogeneic aorta
      transplantation model. Donor rats received no pre-treatment, or tacrolimus,
      methylprednisolone, rapamycin, or mycofenolate mofetil (MMF) 16 and 2h before
      explantation of the grafts. Eight weeks after transplantation, aorta allografts
      were harvested. Percent intima area/intima+media area (I/I+M), inflammatory cells
      and in situ MMP-2 and -9 activity were determined. In pre-transplantation
      biopsies, MMP-2 and -9 ratio, and mRNA levels for genes of interest were
      determined. In pre-transplantation biopsies we found no differences in MMP-2/9
      ratio, and Bcl-2, Bax, TGF-beta, HO-1, p21, and HIF-1alpha mRNA expression
      between the groups. Aorta allografts, pre-treated with tacrolimus, showed
      significantly lower I/I+M ratio compared to untreated controls (p<0.01). Pre
      treatment with methylprednisolone, rapamycin or MMF did not significantly reduce
      I/I+M ratio. In situ MMP-2/MMP-9 activity was significantly reduced in grafts
      treated with tacrolimus and rapamycin compared to controls (p<0.05).
      Immunohistochemistry revealed a high number of CD4+ cells and high CD4/CD8 ratio
      in grafts pre-treated with tacrolimus. Donor pre-treatment with tacrolimus
      significantly reduces transplant arteriosclerosis and is associated with reduced
      in situ MMP-2/MMP-9 activity and increased number of CD4+ cells.

PMID- 19162190
TI  - The Warburg Effect returns to the cancer stage.

PMID- 19162192
TI  - TrkA pathway activation induced by amyloid-beta (Abeta).
AB  - Amyloid-beta (Abeta), a cytotoxic fragment of Amyloid Precursor Protein (APP),
      has been implicated in the etiopathogenesis of Alzheimer's disease (AD). Since
      several neurotrophins signalling pathways may be activated in response to toxic
      insults, we investigated whether a similar response is triggered also by Abeta.
      After Abeta (25-35) peptide administration to cultured rat hippocampal neurons,
      the nerve growth factor (NGF) and its receptor (TrkA) mRNA expression is up
      regulated. Moreover, we observe an increased cellular TrkA expression (4.5 fold)
      and NGF release in the culture medium (5-fold). Concomitantly, TrkA, Akt and
      glycogen synthase kinase 3beta (Gsk3beta) phosphorylation significantly increase.
      Interestingly, when cells were treated with Abeta (25-35) in the presence of
      blocking antibody against NGF, only a partial TrkA activation (2-fold) was
      observed. These results have been confirmed by using pathophysiological Abeta (1
      42) oligomers. Our data provide the evidence that Abeta induces the TrkA pathway
      activation directly by itself and indirectly promoting NGF secretion.

PMID- 19162191
TI  - N-cadherin modulates voltage activated calcium influx via RhoA, p120-catenin, and
      myosin-actin interaction.
AB  - N-cadherin is a transmembrane adhesion receptor that contributes to neuronal
      development and synapse formation through homophilic interactions that provide
      structural-adhesive support to contacts between cell membranes. In addition, N
      cadherin homotypic binding may initiate cell signaling that regulates neuronal
      physiology. In this study, we investigated signaling capabilities of N-cadherin
      that control voltage activated calcium influx. Using whole-cell voltage clamp
      recording of isolated inward calcium currents in freshly isolated chick ciliary
      ganglion neurons we show that the juxtamembrane region of N-cadherin cytoplasmic
      domain regulates high-threshold voltage activated calcium currents by interacting
      with p120-catenin and activating RhoA. This regulatory mechanism requires myosin
      interaction with actin. Furthermore, N-cadherin homophilic binding enhanced
      voltage activated calcium current amplitude in dissociated neurons that have
      already developed mature synaptic contacts in vivo. The increase in calcium
      current amplitude was not affected by brefeldin A suggesting that the effect is
      caused via direct channel modulation and not by increasing channel expression. In
      contrast, homotypic N-cadherin interaction failed to regulate calcium influx in
      freshly isolated immature neurons. However, RhoA inhibitors enhanced calcium
      current amplitude in these immature neurons, suggesting that the inhibitory
      effect of RhoA on calcium entry is regulated during neuronal development and
      synapse maturation. These results indicate that N-cadherin modulates voltage
      activated calcium entry by a mechanism that involves RhoA activity and its
      downstream effects on the cytoskeleton, and suggest that N-cadherin provides
      support for synaptic maturation and sustained synaptic activity by facilitating
      voltage activated calcium influx.

PMID- 19162194
TI  - A dual-functional E. coli vector for expressing recombinant protein with high
      solubility and antigen presentation ability.
AB  - A dual-functional Escherichia coli expression vector capable of producing soluble
      recombinant proteins with high immunogenicity in animals is introduced. This
      vector expresses polypeptides fused to a PTD-J-domain peptide. The J-domain
      peptide is derived from murine Hsp40 by using optimized codons for E. coli. The
      association of the J-domain to the nucleotide binding domain of the DnaK
      chaperone increases the probability that the fused polypeptide will be folded by
      the DnaK and hence increases the solubility of the recombinant protein. The PTD-J
      domain can also enhance the immunogenicity of the fused chicken IGF-I polypeptide
      as well as an oligo-peptide derived from haptoglobin in rodents, possibly via the
      association with either the extracellular or intracellular Hsp70 proteins.

PMID- 19162193
TI  - A novel bicistronic vector for overexpressing Mycobacterium tuberculosis proteins
      in Escherichia coli.
AB  - A putative DNA glycosylase encoded by the Rv3297 gene (MtuNei2) has been
      identified in Mycobacterium tuberculosis. Our efforts to express this gene in
      Escherichia coli either by supplementing tRNAs for rare codons or optimizing the
      gene with preferred codons for E. coli resulted in little or no expression. On
      the other hand, high-level expression was observed using a bicistronic expression
      vector in which the target gene was translationally coupled to an upstream leader
      sequence. Further comparison of the predicted mRNA secondary structures supported
      the hypothesis that mRNA secondary structure(s) surrounding the translation
      initiation region (TIR), rather than codon usage, played the dominant role in
      influencing translation efficiency, although manipulation of codon usage or tRNA
      supplementation did further enhance expression in the bicistronic vector.
      Addition of a cleavable N-terminal tag also facilitated gene expression in E.
      coli, possibly through a similar mechanism. However, since cleavage of N-terminal
      tags is determined by the amino acid at the P(1)' position downstream of the
      protease recognition sequence and results in the addition of an extra amino acid
      in front of the N-terminus of the protein, this strategy is not particularly
      amenable to Fpg/Nei family DNA glycosylases which carry the catalytic proline
      residue at the P(1)' position and require a free N-terminus. On the other hand,
      the bicistronic vector constructed here is potentially valuable particularly when
      expressing proteins from G/C rich organisms and when the proteins carry proline
      residues at the N-terminus in their native form. Thus the bicistronic expression
      system can be used to improve translation efficiency of mRNAs and achieve high
      level expression of mycobacterial genes in E. coli.

PMID- 19162195
TI  - Tannic acid-mediated osmium impregnation after freeze-substitution: a strategy to
      enhance membrane contrast for electron tomography.
AB  - In this technical note we report a tannic acid-mediated osmium impregnation
      method that, applied after freeze-substitution, increases membrane contrast in
      cells for transmission electron microscopy and tomography studies. The general
      staining that is achieved allows visualization of organelles, plasma membrane and
      associated specializations (e.g. caveolae) in non-post-stained plastic sections
      by conventional transmission electron microscopy. In combination with electron
      tomography it results in membranes with a proper contrast and equal staining
      pattern through the depth of the tomograms. The protocol that we contribute can
      serve as starting point for those willing to improve the membrane contrast of
      their specimens or to make 3D studies on the architecture of membranous
      compartments by electron tomography.

PMID- 19162196
TI  - AcrB et al.: Obstinate contaminants in a picogram scale. One more bottleneck in
      the membrane protein structure pipeline.
AB  - Heterologous expression of integral membrane proteins from Helicobacter pylori
      26695 in Escherichia coli enabled the identification of 17 candidates for
      purification and subsequent crystallization. 45% of the purified proteins were
      contaminated with what was later identified as the multidrug efflux pump (AcrB)of
      E. coli, and 17% with the succinate dehydrogenase. While additional purification
      steps ensured removal of succinate dehydrogenase, they failed to remove AcrB
      completely, leaving picogram amounts present infractions intended for 3D
      crystallization. Two of these targets, the Na+ dependent D-glucose/D-galactose
      transporter (GluP-HP1174) and the carbon starvation protein A (CstA-HP1168),
      produced small crystals(<40 lm). Crystals from the GluP preparation diffracted to
      4.2 A resolution and belonged to the rhombohedral space group H32. Subsequent
      molecular replacement proved that these crystals were derived from a contaminant,
      the efflux transporter AcrB. This unexpected crystallization of AcrB from
      picogram amounts was observed in six new conditions. The systematic occurrence of
      AcrB in membrane preparations stems from the upregulation of its transcription in
      response to the stress induced by the expression of a selected target. This,
      along with its tendency to crystallize in the picogram scale, poses a serious
      concern in membrane protein expression using heterologous hosts harbouring AcrB.

PMID- 19162197
TI  - F-type lectin from the sea bass (Dicentrarchus labrax): purification, cDNA
      cloning, tissue expression and localization, and opsonic activity.
AB  - Recently described biochemical and structural aspects of fucose-binding lectins
      from the European eel (Anguilla anguilla) and striped bass (Morone saxatilis) led
      to the identification of a novel lectin family ("F-type" lectins) characterized
      by a unique sequence motif and a characteristic structural fold. The F-type fold
      is shared not only with other members of this lectin family, but also with
      apparently unrelated proteins ranging from prokaryotes to vertebrates. Here we
      describe the purification, biochemical and molecular properties, and the opsonic
      activity of an F-type lectin (DlFBL) isolated from sea bass (Dicentrarchus
      labrax) serum. DlFBL exhibits two tandemly arranged carbohydrate-recognition
      domains that display the F-type sequence motif. In situ hybridization and
      immunohistochemical analysis revealed that DlFBL is specifically expressed and
      localized in hepatocytes and intestinal cells. Exposure of formalin-killed
      Escherichia coli to DlFBL enhanced their phagocytosis by D. labrax peritoneal
      macrophages relative to the unexposed controls, suggesting that DlFBL may
      function as an opsonin in plasma and intestinal mucus.

PMID- 19162198
TI  - A comparison of automated segmentation and manual tracing for quantifying
      hippocampal and amygdala volumes.
AB  - Large databases of high-resolution structural MR images are being assembled to
      quantitatively examine the relationships between brain anatomy, disease
      progression, treatment regimens, and genetic influences upon brain structure.
      Quantifying brain structures in such large databases cannot be practically
      accomplished by expert neuroanatomists using hand-tracing. Rather, this research
      will depend upon automated methods that reliably and accurately segment and
      quantify dozens of brain regions. At present, there is little guidance available
      to help clinical research groups in choosing such tools. Thus, our goal was to
      compare the performance of two popular and fully automated tools, FSL/FIRST and
      FreeSurfer, to expert hand tracing in the measurement of the hippocampus and
      amygdala. Volumes derived from each automated measurement were compared to hand
      tracing for percent volume overlap, percent volume difference, across-sample
      correlation, and 3-D group-level shape analysis. In addition, sample size
      estimates for conducting between-group studies were computed for a range of
      effect sizes. Compared to hand tracing, hippocampal measurements with FreeSurfer
      exhibited greater volume overlap, smaller volume difference, and higher
      correlation than FIRST, and sample size estimates with FreeSurfer were closer to
      hand tracing. Amygdala measurement with FreeSurfer was also more highly
      correlated to hand tracing than FIRST, but exhibited a greater volume difference
      than FIRST. Both techniques had comparable volume overlap and similar sample size
      estimates. Compared to hand tracing, a 3-D shape analysis of the hippocampus
      showed FreeSurfer was more accurate than FIRST, particularly in the head and
      tail. However, FIRST more accurately represented the amygdala shape than
      FreeSurfer, which inflated its anterior and posterior surfaces.

PMID- 19162199
TI  - Identifying reliable independent components via split-half comparisons.
AB  - Independent component analysis (ICA) is a family of unsupervised learning
      algorithms that have proven useful for the analysis of the electroencephalogram
      (EEG) and magnetoencephalogram (MEG). ICA decomposes an EEG/MEG data set into a
      basis of maximally temporally independent components (ICs) that are learned from
      the data. As with any statistic, a concern with using ICA is the degree to which
      the estimated ICs are reliable. An IC may not be reliable if ICA was trained on
      insufficient data, if ICA training was stopped prematurely or at a local minimum
      (for some algorithms), or if multiple global minima were present. Consequently,
      evidence of ICA reliability is critical for the credibility of ICA results. In
      this paper, we present a new algorithm for assessing the reliability of ICs based
      on applying ICA separately to split-halves of a data set. This algorithm improves
      upon existing methods in that it considers both IC scalp topographies and
      activations, uses a probabilistically interpretable threshold for accepting ICs
      as reliable, and requires applying ICA only three times per data set. As evidence
      of the method's validity, we show that the method can perform comparably to more
      time intensive bootstrap resampling and depends in a reasonable manner on the
      amount of training data. Finally, using the method we illustrate the importance
      of checking the reliability of ICs by demonstrating that IC reliability is
      dramatically increased by removing the mean EEG at each channel for each epoch of
      data rather than the mean EEG in a prestimulus baseline.

PMID- 19162201
TI  - FMRI evidence of a functional network setting the criteria for withholding a
      response.
AB  - That the left prefrontal cortex has a critical role setting response criteria for
      numerous tasks has been well established, but gaps remain in our understanding of
      the brain mechanisms of task-setting. We aimed at (i) testing the involvement of
      this region in setting the criteria for a non-response and (ii) assessing
      functional connectivity between this and other brain regions involved in task
      setting. Fourteen young participants performed a go/nogo task during functional
      magnetic resonance imaging. The task included two nogo visual stimuli which
      elicit a high (distractor) or a low (other) tendency to respond, respectively.
      Two task blocks were examined to assess learning the criteria. First, a
      multivariate Partial Least Squares (PLS) analysis identified brain regions that
      co-varied with task conditions, as expressed by two significant Latent Variables
      (LVs). One LV distinguished go and nogo stimuli. The other LV identified regions
      involved in the first block when the criteria not to respond to distractors were
      established. The left prefrontal region was prominently involved. Second, a left
      ventrolateral prefrontal area was selected from this LV as a seed region to
      perform functional connectivity using a multi-block PLS analysis. Results showed
      a distributed network functionally connected with the seed, including superior
      medial prefrontal and left superior parietal regions. These findings extend our
      understanding of task-setting along the following dimensions: 1) even when a task
      requires withholding a response, the left prefrontal cortex has a critical role
      in setting criteria, and 2) this region responds to the task demands within a
      distinctive functional network.

PMID- 19162200
TI  - Lack of generalizability of sex differences in the fMRI BOLD activity associated
      with language processing in adults.
AB  - A lack of consensus exists as to whether there are sex differences in the fMRI
      BOLD signal correlates of language processing in the human brain. Here, whole
      brain fMRI was used to examine the neural activity of 46 adults performing one of
      two sets of language tasks. Conservative quantitative and qualitative criteria
      identified a handful of statistically significant regions of "sex difference"
      within each task separately. When each of the two sets of regions was
      investigated in the group of subjects performing the other task set, however,
      most of the identified "sex differences" failed to generalize. Identical analyses
      of the same subjects divided into sex-matched pseudorandom control groups for
      each task set separately revealed that it is possible to observe a similar number
      of statistically significant regions of "group difference" in the task-associated
      BOLD signal, even when the groups do not differ on any of the measured behavioral
      parameters, or any obvious demographic characteristic. Together, these results
      suggest that one should be cautious when interpreting studies that purport to
      have identified regions of difference between groups, whether those groups are
      divided by sex or by any other criterion. In particular, generalization or
      replication of a result in independent data sets is necessary for establishing
      conclusive support for any hypothesis about differences in brain function between
      groups.

PMID- 19162202
TI  - Role of medial cortical, hippocampal and striatal interactions during cognitive
      set-shifting.
AB  - To date, few studies have examined the functional connectivity of brain regions
      involved in complex executive function tasks, such as cognitive set-shifting. In
      this study, eighteen healthy volunteers performed a cognitive set-shifting task
      modified from the Wisconsin card sort test while undergoing functional magnetic
      resonance imaging. These modifications allowed better disambiguation between
      cognitive processes and revealed several novel findings: 1) peak activation in
      the caudate nuclei in the first instance of negative feedback signaling a shift
      in rule, 2) lowest caudate activation once the rule had been identified, 3) peak
      hippocampal activation once the identity of the rule had been established, and 4)
      decreased hippocampal activation during the generation of new rule candidates.
      This pattern of activation across cognitive set-shifting events suggests that the
      caudate nuclei play a role in response generation when the identity of the new
      rule is unknown. In contrast, the reciprocal pattern of hippocampal activation
      suggests that the hippocampi help consolidate knowledge about the correct
      stimulus-stimulus associations, associations that become inappropriate once the
      rule has changed. Functional connectivity analysis using Granger Causality
      Mapping revealed that caudate and hippocampal regions interacted indirectly via a
      circuit involving the medial orbitofrontal and posterior cingulate regions, which
      are known to bias attention towards stimuli based on expectations built up from
      task-related feedback. Taken together, the evidence suggests that these medial
      regions may mediate striato-hippocampal interactions and hence affect goal
      directed attentional transitions from a response strategy based on stimulus
      reward heuristics (caudate-dependent) to one based on stimulus-stimulus
      associations (hippocampus-dependent).

PMID- 19162203
TI  - Forward and backward connections in the brain: a DCM study of functional
      asymmetries.
AB  - In this paper, we provide evidence for functional asymmetries in forward and
      backward connections that define hierarchical architectures in the brain. We
      exploit the fact that modulatory or nonlinear influences of one neuronal system
      on another (i.e., effective connectivity) entail coupling between different
      frequencies. Functional asymmetry in forward and backward connections was
      addressed by comparing dynamic causal models of MEG responses induced by visual
      processing of normal and scrambled faces. We compared models with and without
      nonlinear (between-frequency) coupling in both forward and backward connections.
      Bayesian model comparison indicated that the best model had nonlinear forward and
      backward connections. Using the best model we then quantified frequency-specific
      causal influences mediating observed spectral responses. We found a striking
      asymmetry between forward and backward connections; in which high (gamma)
      frequencies in higher cortical areas suppressed low (alpha) frequencies in lower
      areas. This suppression was significantly greater than the homologous coupling in
      the forward connections. Furthermore, exactly the asymmetry was observed when we
      examined face-selective coupling (i.e., coupling under faces minus scrambled
      faces). These results highlight the importance of nonlinear coupling among brain
      regions and point to a functional asymmetry between forward and backward
      connections in the human brain that is consistent with anatomical and
      physiological evidence from animal studies. This asymmetry is also consistent
      with functional architectures implied by theories of perceptual inference in the
      brain, based on hierarchical generative models.

PMID- 19162204
TI  - Combined spatial and non-spatial prior for inference on MRI time-series.
AB  - When modelling FMRI and other MRI time-series data, a Bayesian approach based on
      adaptive spatial smoothness priors is a compelling alternative to using a
      standard generalized linear model (GLM) on presmoothed data. Another benefit of
      the Bayesian approach is that biophysical prior information can be incorporated
      in a principled manner; however, this requirement for a fixed non-spatial prior
      on a parameter would normally preclude using spatial regularization on that same
      parameter. We have developed a Gaussian-process-based prior to apply adaptive
      spatial regularization while still ensuring that the fixed biophysical prior is
      correctly applied on each voxel. A parameterized covariance matrix provides
      separate control over the variance (the diagonal elements) and the between-voxel
      correlation (due to off-diagonal elements). Analysis proceeds using evidence
      optimization (EO), with variational Bayes (VB) updates used for some parameters.
      The method can also be applied to non-linear forward models by using a linear
      Taylor expansion centred on the latest parameter estimates. Applying the method
      to FMRI with a constrained haemodynamic response function (HRF) shape model shows
      improved fits in simulations, compared to using either the non-spatial or spatial
      smoothness prior alone. We also analyse multi-inversion arterial spin labelling
      data using a non-linear perfusion model to estimate cerebral blood flow and bolus
      arrival time. By combining both types of prior information, this new prior
      performs consistently well across a wider range of situations than either prior
      alone, and provides better estimates when both types of prior information are
      relevant.

PMID- 19162205
TI  - Optic nerve diffusion changes and atrophy jointly predict visual dysfunction
      after optic neuritis.
AB  - Recently, there has been strong interest in the development of imaging techniques
      to quantify axonal and myelin pathology in patients with multiple sclerosis (MS).
      Optic neuritis, a condition characterised by inflammatory demyelination of the
      optic nerve, is one of the commonest sites of MS relapse, and exhibits similar
      pathological alterations to MS lesions elsewhere in the central nervous system
      (CNS). Unlike other regions of the CNS, however, the function of the optic nerve
      can be accurately assessed using clinical measures, as well as
      electrophysiological techniques such as visual evoked potential recordings.
      Therefore, optic neuritis is useful for investigating the relationship between
      abnormalities in optic nerve structure, assessed using magnetic resonance imaging
      (MRI), and visual dysfunction, assessed clinically and electrophysiologically.
      The aims of the present study were to assess optic nerve structural abnormalities
      in patients with a history of unilateral optic neuritis using MRI, and then to
      identify correlations between abnormalities in optic nerve MRI and visual
      dysfunction. Ten controls and sixteen patients underwent high resolution optic
      nerve diffusion tensor imaging (DTI), T2- and T1-weighted MRI. In addition,
      Snellen visual acuity and the latency and amplitude of multifocal visual evoked
      potentials (mfVEP) were tested in all patients. Diffusion and volumetric MRI
      indices were correlated to mfVEP functional indices. Significant abnormalities
      were detected in MRI and mfVEP measures in patients' affected nerves compared to
      unaffected optic nerves or optic nerves from healthy controls. Reduced mfVEP
      amplitude in the affected side significantly correlated with both affected optic
      nerve atrophy (R=0.58, p=0.02) and reduced fractional anisotropy (FA) (R=0.52,
      p=0.04). However, atrophy and reduced FA did not correlate with each other. To
      further investigate this disassociation, we used linear regression analysis with
      optic nerve atrophy and optic nerve FA as independent variables and mfVEP
      amplitude as the dependent variable. The resulting linear regression model was
      highly significant (R=0.819, p=0.001). These results show that, 4 years after
      unilateral optic neuritis, MRI-based measures of optic nerve structural
      abnormalities (decreased anisotropy and volume) independently predict visual
      dysfunction.

PMID- 19162206
TI  - Exploratory structural equation modeling of resting-state fMRI: applicability of
      group models to individual subjects.
AB  - The extension of group-level connectivity methods to individual subjects remains
      a hurdle for statistical analyses of neuroimaging data. Previous group analyses
      of positron emission tomography data in clinically depressed patients, for
      example, have shown that resting-state connectivity prior to therapy predicts how
      patients eventually respond to pharmacological and cognitive-behavioral therapy.
      Such applications would be considerably more informative for clinical decision
      making if these connectivity methods could be extended into the individual
      subject domain. To test such an extension, 46 treatment-naive depressed patients
      were enrolled in an fMRI study to model baseline resting-state functional
      connectivity. Resting-state fMRI scans were acquired and submitted to exploratory
      structural equation modeling (SEM) to derive the optimal group connectivity
      model. Jackknife and split sample tests confirm that group model was highly
      reproducible, and path weights were consistent across the best five group models.
      When this model was applied to data from individual subjects, 85% of patients fit
      the group model. Histogram analysis of individual subjects' paths indicate that
      some paths are better representative of group membership. These results suggest
      that exploratory SEM is a viable technique for neuroimaging connectivity analyses
      of individual subjects' resting-state fMRI data.

PMID- 19162207
TI  - Intraspecific evolution of Canarian Euchloe (Lepidoptera: Pieridae) butterflies,
      based on mtDNA sequences.

PMID- 19162208
TI  - Porphyromonas gingivalis with either Tannerella forsythia or Treponema denticola
      induces synergistic IL-6 production by murine macrophage-like J774.1 cells.
AB  - BACKGROUND: Chronic periodontitis is caused by mixed bacterial infection.
      Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola are
      frequently detected in deep periodontal pockets. We demonstrate that these
      bacteria induce proinflammatory cytokine production by the mouse macrophage-like
      cell line J774.1. MATERIALS AND METHODS: J774.1 cells were incubated with and
      without bacteria for 24h in 96-well flat-bottomed plates. The culture
      supernatants were analyzed by enzyme-linked immunosorbent assay for secreted
      mouse interleukin (IL)-6, monocyte chemoattractant protein-1, IL-23, IL-1 beta
      and tumor necrosis factor-alpha. The cytokine concentrations were determined
      using a standard curve prepared for each assay. RESULTS: Mixed infection with P.
      gingivalis and either T. forsythia or T. denticola at 10(5)CFU/ml acted
      synergistically to increase IL-6 production, but not monocyte chemoattractant
      protein-1, IL-23, IL-1 beta or tumor necrosis factor-alpha production. Gingipain
      inhibitors KYT-1 and KYT-36 inhibited IL-6 production by J774.1 cells incubated
      with 10(5)CFU/ml of mixed bacteria. CONCLUSION: These results suggest that P.
      gingivalis with either T. forsythia or T. denticola directly induces synergistic
      IL-6 protein production and that gingipains play a role in this synergistic
      effect.

PMID- 19162209
TI  - Salivary detection of periodontopathic bacteria and periodontal health status in
      dental students.
AB  - OBJECTIVE: Saliva may become a potential source of contamination through vertical
      and horizontal transmissions as well as cross-infections. This study aims to use
      saliva as a screening tool to detect putative periodontal pathogens in a young
      population with fairly good oral hygiene. MATERIALS AND METHODS: Stimulated
      saliva samples were obtained from 134 dental students (20.5+/-1 years, range 18
      22 years). Among those, 77 subjects also completed a periodontal examination
      including attachment loss, modified dental, gingival and plaque indices (AL, mDI,
      GI and PI). The test bacteria were identified using a 16S rRNA-based PCR
      detection method. RESULTS: One or more of the test bacteria was found in 67% of
      the subjects. Prevotella nigrescens was detected as single bacterium in 16% of
      the subjects followed by Treponema denticola (4%), Porphyromonas gingivalis (2%),
      Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans (1%) and
      Tannerella forsythia (1%). Two or more pathogens were detected in 42% of the
      subjects. Clinical examination revealed health with no attachment loss (AL) in
      84% of the students. In no AL group, 38% of the students were pathogen free while
      this was 25% for students in localized AL group (p>0.05). There was a
      statistically significant association between the detection of salivary
      periodontal pathogen in general and higher PI (p=0.018) and GI (p=0.043).
      CONCLUSION: Within the limits of this study, it is possible to detect all six
      periodontal pathogens in the saliva of dental students. Although a correlation
      can be observed between the presence of salivary periodontal pathogen and
      clinical signs of inflammation such as plaque accumulation and gingival bleeding,
      detection of specific bacteria in saliva is not related to the presence of
      localized AL based on the presented study population.

PMID- 19162210
TI  - gamma-Secretase in biology and medicine.
AB  - gamma-Secretase is a membrane-embedded proteolytic complex composed of presenilin
      and three other subunits. The gamma-secretase complex generates the amyloid beta
      peptide of Alzheimer's disease but also plays important roles in normal
      physiology, especially in signaling from the Notch receptor. How this hydrolytic
      enzyme works in a hydrophobic environment is largely unanswered, but mutagenesis
      and chemical probes have offered insight. gamma-Secretase is an important
      therapeutic target, although mechanism-based toxicity presents a serious
      obstacle. Agents that lower amyloid beta-peptide production while leaving
      important normal functions of gamma-secretase intact are promising therapeutic
      leads. Inhibition of Notch signaling by gamma-secretase inhibitors, which is
      undesirable for the prevention or treatment of Alzheimer's disease, may be
      beneficial for the treatment of a variety of cancers.

PMID- 19162211
TI  - Hyperoxia exaggerates bacterial dissemination and lethality in Pseudomonas
      aeruginosa pneumonia.
AB  - Effects of hyperoxia on lethality in mice with Pseudomonas aeruginosa pneumonia
      were defined, and protective roles of macrolides were examined both in vitro and
      in vivo. Sub-lethal hyperoxia accelerated lethality of mice with P. aeruginosa
      pneumonia. Bacterial number was not different in the lungs, but higher in the
      liver of mice in hyperoxic conditions. Filter-sterilized culture supernatants of
      bacteria induced loss of viability of alveolar epithelial cells, which was
      exaggerated in hyperoxia. Metalloprotease blocking by inhibitor or gene
      disruption in bacteria resulted in partial reduction of cytotoxic activity in
      culture supernatants. Co-culture of bacteria with sub-inhibitory concentrations
      of macrolides, such as azithromycin, reduced cytotoxic activity in the culture
      supernatants. Azithromycin provided significant survival benefit in hyperoxia
      pneumonia model, which was associated with suppression of bacterial dissemination
      to extra-pulmonary organs. These results suggest that hyperoxia serves as an
      important cofactor for bacterial dissemination and lethality of P. aeruginosa
      pneumonia. Our data identify the potential of macrolides to protect individuals
      with P. aeruginosa pneumonia in the setting of hyperoxia.

PMID- 19162212
TI  - Basal metabolism is correlated with habitat productivity among populations of
      degus (Octodon degus).
AB  - Several competing hypotheses attempt to explain how environmental conditions
      affect mass-independent basal metabolic rate (BMR) in mammals. One of the most
      inclusive is the hypothesis that associates BMR with food habits, including
      habitat productivity. The effects of food habits have been widely investigated at
      the interspecific level, and variation between individuals and populations has
      been largely ignored. Intraspecific analysis of physiological traits has the
      potential to compensate for many pitfalls associated with interspecific analyses
      and serve as a useful approach for evaluating hypotheses regarding metabolic
      adaptation. Here we tested the effects of climatic variables (mean annual
      rainfall=PP, mean annual temperature=T(A)), net primary productivity (NPP) and
      the de Martonne index (DMi) of aridity on mass-independent BMR among four
      populations of the caviomorph rodent Octodon degus along a geographic gradient in
      Chile. BMR was measured on animals maintained in a common garden acclimation set
      up, thus kept under the same environment and diet quality for at least 6 months.
      Mass-independent BMR was significantly different among degu populations showing a
      large intraspecific spread in metabolic rates. A very large fraction of
      interpopulational variability in mass-independent BMR was explained by NPP, PP
      and DMi. Our results were conclusive about the effects of habitat productivity on
      setting the level of mass-independent BMR at the intraspecific-interpopulational
      level.

PMID- 19162213
TI  - In vivo regulation of GLUT2 mRNA in sea bass (Dicentrarchus labrax) in response
      to acute and chronic hypoxia.
AB  - The expression and regulation of sodium-independent glucose transporter (GLUT)-2,
      in relation to hypoxia has not yet been explored in fish or other vertebrates. In
      this study, the complete open-reading frame for sea bass GLUT2 was isolated and
      deposited in the GenBank. The predicted 12 transmembrane domains of the protein
      (508 amino acids) are presented. A phylogenetic tree was constructed on GLUT2
      sequences of sea bass and those of other teleost, amphibian, avian, and mammalian
      species. We also analyzed acute and chronic hypoxia-induced changes in the
      expression of hepatic GLUT2 mRNA, using one-tube, two-temperature, real-time RT
      PCR with which gene expression can be absolutely quantified by the standard curve
      method. The number of GLUT2 mRNA copies was significantly increased in response
      to both acute (1.9 mg/L, dissolved oxygen for 4 h) and chronic (4.3 mg/L, DO for
      15 days) hypoxia conditions. The hypoxia-related changes in GLUT2 mRNA copy
      number support the view that GLUT2 is involved in the adaptation response to
      hypoxia in sea bass, a marine hypoxia-sensitive species. We realize that the
      GLUT2 mRNA levels in our study do not measure the physiological effects produced
      by the protein. Thus, we can only speculate that, under hypoxic conditions, GLUT2
      probably functions to allow the glucose produced from liver glycogen to leave the
      hepatocytes.

PMID- 19162214
TI  - Characterization of the 5'-flanking regions of the sea anemone ADP ribosylation
      factor 1 and actin genes.
AB  - The 5'-flanking regions of the sea anemone, Aiptasia pulchella (ap) ARF1 gene
      showed the absence of a TATA box. The transcriptional start site determined by 5'
      rapid amplification of cDNA ends (5'RACE) is located 75 base pairs upstream of
      the translational start site. Transfection experiments in HeLa and COS-7 cells
      demonstrate that all the elements required to achieve significant basal
      transcription activity are located between position -208 and -88 relative to the
      transcriptional start site. There are three consensus initiator (Inr) elements
      for TATA-less promoter around the transcriptional start site of the apARF1 gene
      (+29, -158, and -226) that are likely to play roles in the regulation. For the
      apactin gene, the 5'-flanking region contains a TATA box located 30 base pairs
      upstream of the transcriptional start site. The transient transfection of
      apactin/luciferase deletion constructs revealed that the TATA box indeed is
      necessary for full expression.

PMID- 19162215
TI  - Metabolism of hydrogen peroxide in univoltine and polyvoltine strains of silkworm
      (Bombyx mori).
AB  - Recent work has demonstrated that hydrogen peroxide functions as a signaling
      molecule controlling different essential processes in plants and mammals, which
      can be produced by superoxide dismutase (SOD) and xanthine oxidase (XO) and
      decomposed by catalase (CAT), respectively. Progeny diapause of the silkworm,
      Bombyx mori, is induced by diapause hormone (DH) and the expression of DH gene in
      the maternal generation has been determined. In order to investigate the
      relationship between the metabolism of H(2)O(2) and the expression of DH gene,
      level of H(2)O(2) and activities of SOD, XO and CAT between univoltine and
      polyvoltine strains, which can produce diapause and non-diapause eggs,
      respectively, at embryonic and pupal stages were measured. Our results showed
      that there were significant differences in the metabolism of hydrogen peroxide
      between two strains and between embryonic and pupal stages. Compared to
      polyvoltine strain, level of hydrogen peroxide in univoltine strain was
      significantly higher from stage 19 to stage 21 but lower from stage 24 to stage
      29 and the whole pupal stage (Fig. 1). Variations of hydrogen peroxide indicated
      that hydrogen peroxide may be involved in the active release of DH and the
      progeny diapause decision by DH rather than the expression of DH gene.

PMID- 19162216
TI  - Fiber type homogeneity of the flight musculature in small birds.
AB  - Studies of medium- and large-bodied avian species have suggested that variation
      in flight muscle composition is related to differences in flight behavior. For
      example, slow-twitch or tonic fibers are generally found only in the flight
      muscles of non-volant or soaring/gliding birds. However, we know comparatively
      little about fiber composition of the muscles of the smallest birds. Here we
      describe the fiber composition of muscles from the wings, shoulders, and legs of
      two small avian species, which also display very high wingbeat frequencies:
      Anna's hummingbirds (Calypte anna) and zebra finches (Taeniopygia guttata). All
      flight muscles examined in both species contained exclusively fast oxidative
      glycolytic (FOG) fibers. These unique results suggest that fast oxidative fibers
      are both necessary and sufficient for the full range of flight behaviors in these
      small-bodied birds. Like all other studied birds, the zebra finch gastrocnemius,
      a tarsometatarsal extensor, contained a mixture of FOG (27.1%), slow oxidative
      (SO, 12.7%), and fast glycolytic (FG, 60.2%) fibers. By contrast, the hummingbird
      gastrocnemius lacked FG fibers (85.5% FOG, 14.5% SO), which may reflect the
      reduced role of the hindlimb during take-off. We further hypothesize that
      thermogenic requirements constrain fiber type heterogeneity in these small
      endothermic vertebrates.

PMID- 19162217
TI  - Sphingosine kinase 1 is essential for proteinase-activated receptor-1 signalling
      in epithelial and endothelial cells.
AB  - There is accumulating evidence that activation of sphingosine kinase 1 (SPHK1) is
      an important element in intracellular signalling cascades initiated by
      stimulation of multiple receptors, including certain growth factor, cytokine, and
      also G-protein coupled receptors. We here report that stimulation of the lung
      epithelial cell line A549 by thrombin leads to transient increase of SPHK1
      activity and elevation of intracellular sphingosine-1-phosphate (S1P); abrogation
      of this stimulation by SPHK1-specific siRNA, pharmacological inhibition, or
      expression of a dominant-negative SPHK1 mutant blocks the response to thrombin,
      as measured by secretion of MCP-1, IL-6, IL-8, and PGE(2). Using selective
      stimulation of proteinase-activated receptors (PARs) a specific involvement of
      SPHK1 in the PAR-1 induced responses in A549 cell, including activation of
      NFkappaB, was evident, while PAR-2 and PAR-4 responses were independent of SPHK1.
      Moreover, PAR-1 or thrombin-induced cytokine production and adhesion factor
      expression of human umbilical vein endothelial cells was also seen to depend on
      SPHK1. Using dermal microvascular endothelial cells from SPHK1-deficient mice, we
      showed that absence of the enzyme abrogates MCP-1 production induced in these
      cells upon treatment with thrombin or PAR-1 activating peptide. We propose SPHK1
      inhibition as a novel way to block PAR-1 mediated signalling, which could be
      useful in treatment of a number of diseases, in particular in atherosclerosis.

PMID- 19162218
TI  - Biologics and postbiologics: novel immunotherapeutics for the induction and
      maintenance of remission.
AB  - Rapid growth in the development of new tools and advances in molecular immunology
      has led to a class of drugs called biologics. While effective, these therapies
      are costly, typically require continuous administration and often have serious
      side effects. This review focuses on current therapies and the need for a new
      class of therapies. A novel class of drugs able to induce and maintain tolerance
      will be paralleled with the notion that combination therapy appropriately
      tailored to patient subpopulations may hold the promise of less costly and more
      effective therapy.

PMID- 19162219
TI  - Early integration of pharmacokinetic and dynamic reasoning is essential for
      optimal development of lead compounds: strategic considerations.
AB  - The aims of this report are firstly to raise awareness among kineticists and
      pharmacologists as to why pharmacokinetic-pharmacodynamic (PKPD) integration is
      essential for target validation (TV), optimizing development of lead compounds
      (lead generation [LG] and lead optimization [LO]) and scaling these to human. A
      related aim is to demonstrate strategic examples of PKPD collaborations that have
      improved the planning, execution and evaluation of experiments in primary and
      safety pharmacology. Examples include design of TV studies, design and data
      'pruning' of PKPD studies in LO, analysis of data with marginal and substantial
      temporal (time) differences between exposure and response, design of safety
      pharmacology studies, assessment of safety margin and assessment of uncertainties
      in predictions of first dose in human.

PMID- 19162220
TI  - Thioureides of 2-(phenoxymethyl)benzoic acid 4-R substituted: a novel class of
      anti-parasitic compounds.
AB  - Fifty members of a novel class of antimicrobial compounds, 2-(4-R
      phenoxymethyl)benzoic acid thioureides, were synthesized and characterized with
      respect to their activities against three parasites of human relevance, namely
      the protozoa Giardia lamblia and Toxoplasma gondii, and the larval (metacestode)
      stage of the tapeworm Echinococcus multilocularis. To determine the selective
      toxicity of these compounds, the human colon cancer cell line Caco2 and primary
      cultures of human foreskin fibroblasts (HFF) were also investigated. The new
      thioureides were obtained in a three-step-reaction process and subsequently
      characterized by their physical constants (melting point, solubility). The
      chemical structures were elucidated by (1)H NMR, (13)C NMR, IR spectral methods
      and elemental analysis. The analyses confirmed the final and intermediate
      compound structures and the synthesis. The compounds were then tested on the
      parasites in vitro. All thioureides, except two compounds with a nitro group,
      were totally ineffective against Giardia lamblia. 23 compounds inhibited the
      proliferation of T. gondii, three of them with an IC(50) of approximately 1
      microM. The structural integrity of E. multilocularis metacestodes was affected
      by 22 compounds. In contrast, HFF were not susceptible to any of these
      thioureides, while Caco2 cells were affected by 17 compounds, two of them
      inhibiting proliferation with an IC(50) in the micromolar range. Thioureides may
      thus present a promising class of anti-infective agents.

PMID- 19162221
TI  - Human plasma phospholipid transfer protein specific activity is correlated with
      HDL size: implications for lipoprotein physiology.
AB  - To gain further insights into the relationship between plasma phospholipid
      transfer protein (PLTP) and lipoprotein particles, PLTP mass and phospholipid
      transfer activity were measured, and their associations with the level and size
      of lipoprotein particles examined in 39 healthy adult subjects. No bivariate
      correlation was observed between PLTP activity and mass. PLTP activity was
      positively associated with cholesterol, triglyceride, apo B and VLDL particle
      level (r(s)=0.40-0.56, p< or =0.01) while PLTP mass was positively associated
      with HDL-C, large HDL particles, and mean LDL and HDL particle sizes (r(s)=0.44
      0.52, p<0.01). Importantly, plasma PLTP specific activity (SA) was significantly
      associated with specific lipoprotein classes, positively with VLDL, IDL, and
      small LDL particles (r(s)=0.42-0.62, p< or =0.01) and inversely with large LDL,
      large HDL, and mean LDL and HDL particle size (r(s)=-0.42 to -0.70, p< or =0.01).
      After controlling for triglyceride levels, the correlation between PLTP mass or
      SA and HDL size remained significant. In linear models, HDL size explained 45% of
      the variability of plasma PLTP SA while triglyceride explained 34% of the PLTP
      activity. Thus, in healthy adults a significant relationship exists between HDL
      size and plasma PLTP SA (r(s)=-0.70), implying that HDL particle size may
      modulate PLTP SA in the vascular compartment.

PMID- 19162223
TI  - Pleonal muscle development in the shrimp Penaeus (Litopenaeus) vannamei
      (Crustacea: Malacostraca: Decapoda: Dendrobranchiata).
AB  - Penaeoidean shrimp pleonal muscle is a valuable economic resource worldwide, but
      little is known of its development during larval stages. The development of
      pleonal muscle in Penaeus (Litopenaeus) vannamei was studied by rhodamine
      phalloidin staining and laser-scanning confocal microscopy. Dorsal pleonal muscle
      was first evident at the protozoea I stage while ventral pleonal muscle was
      present by the protozoea II stage. Identifiable ventral pleonal muscles were
      evident by the protozoea III stage and all ventral muscle types were present in
      the mysis I. The tail flex response began at the mysis stage and growth of
      existing pleonal muscles continued. The pleopods formed during the mysis stages,
      with coxal and basis muscles developed by mysis III. The pleopods became
      functional beginning with the first post-larval stage. We conclude that the
      pleonal muscle pattern of P. vannamei larvae is similar to that of adult Penaeus
      setiferus, and that homologous muscles are present. The major formation of dorsal
      pleonal muscles occurs during the protozoea II stage, while significant
      development of ventral pleonal muscles occurs during the protozoea III stage.

PMID- 19162222
TI  - Lipodystrophies: disorders of adipose tissue biology.
AB  - The adipocytes synthesize and store triglycerides as lipid droplets surrounded by
      various proteins and phospholipids at its surface. Recently, the molecular basis
      of some of the genetic syndromes of lipodystrophies has been elucidated and some
      of these genetic loci have been found to contribute to lipid droplet formation in
      adipocytes. The two main types of genetic lipodystrophies are congenital
      generalized lipodystrophy (CGL) and familial partial lipodystrophy (FPL). So far,
      three CGL loci: 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2),
      Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) and caveolin 1 (CAV1) and
      four FPL loci: lamin A/C (LMNA), peroxisome proliferator-activated receptor gamma
      (PPARG), v-AKT murine thymoma oncogene homolog 2 (AKT2) and zinc metalloprotease
      (ZMPSTE24), have been identified. AGPAT2 plays a critical role in the synthesis
      of glycerophospholipids and triglycerides required for lipid droplet formation.
      Another protein, seipin (encoded by BSCL2 gene), has been found to induce lipid
      droplet fusion. CAV1 is an integral component of caveolae and might contribute
      towards lipid droplet formation. PPARgamma and AKT2 play important role in
      adipogenesis and lipid synthesis. In this review, we discuss and speculate about
      the contribution of various lipodystrophy genes and their products in the lipid
      droplet formation.

PMID- 19162224
TI  - Living environment of persons with severe epilepsy and intellectual disability: a
      prospective study.
AB  - We studied a population with intellectual disability (ID) and epilepsy and
      analyzed aspects of the living environment. Using an epilepsy impact score
      (EPIEK, the Epilepsy Impact Scale Kempenhaeghe), we found that epilepsy is more
      severe in younger persons than in older persons until about age 60 years.
      Individuals with more adaptive behavior had less severe epilepsy. Compared with
      persons with ID, the subjects in this study had fewer sensory problems and many
      more mobility problems, and more often saw a general practitioner. We concluded
      that people with severe epilepsy and ID have, in some ways, the same needs as
      people with only ID, and yet, in other ways (development of adaptive skills and
      aspects of living environment), distinctly different needs.

PMID- 19162225
TI  - Validation of anticonvulsant and sedative activity of six medicinal plants.
AB  - Acanthus montanus, Alchornea laxiflora, Hyptis spicigera, Microglossa pyrifolia,
      Piliostigma reticulatum, and Voacanga africana were evaluated with respect to
      anticonvulsant and sedative activity in mice using animal models (maximal
      electroshock (MES), N-methyl-D-aspartate (NMDA), pentylenetetrazol (PTZ),
      isonicotinic hydrazide acid (INH), picrotoxin (PIC), and strychnine (STR)-induced
      convulsions or turning behavior and diazepam-induced sleep). Acanthus montanus
      protected 66.6% of mice against MES-, PIC-, and STR-induced convulsions and 83.3%
      of mice from PTZ-induced convulsions. Alchornea laxiflora protected 75% and 87.5%
      of mice in the STR and NMDA tests, respectively, at a dose of 120 mg/kg. Hyptis
      spicigera protected 100 and 87.5% of mice against STR- and PTZ-induced
      convulsions, respectively, at a dose of 160 mg/kg. Microglossa pyrifolia
      protected 50% to 100% of mice against convulsions. Piliostigma reticulatum
      protected 62.5% to 100% of mice against convulsions and turning behavior.
      Voacanga africana protected 62.5% to 87.5% of mice against convulsions and
      turning behavior. All of the plants except A. laxiflora also exerted sedative
      activity by strongly increasing the total duration of sleep induced by diazepam.

PMID- 19162226
TI  - Intracarotid propofol testing: a comparative study with amobarbital.
AB  - Twenty-five consecutive patients who underwent the Wada test using propofol as
      anesthetic were compared with 15 randomly selected patients who were tested using
      amobarbital. Time to verbal and nonverbal responses and time to motor power 3/5
      did not differ between the two groups (P>0.05). The number of doses received by
      each patient and the percentage of patients needing more than one dose were
      significantly greater in the propofol group (P<0.005). Only one patient developed
      confusion, combativeness, and agitation. Despite the need for multiple doses, our
      patients had no residual drowsiness within 10 to 15 minutes of the propofol
      injection. This allowed us to perform the test on both sides on the same day
      separated only by 45 minutes. Propofol is an effective alternative to amobarbital
      in the Wada test, and may be used successfully in multiple repeated injections
      within the same test without significant residual sedation or significant adverse
      effects.

PMID- 19162227
TI  - Counseling for driving restrictions in epilepsy and other causes of temporary
      impairment of consciousness: how are we doing?
AB  - In Arizona, other states, and other countries, people who experience a seizure or
      other transient alteration of consciousness may be legally restricted from
      driving. Arizona law requires that people with these conditions submit themselves
      for a medical review, whereas health care providers are not required to report to
      the authorities. Therefore, counseling people with these medical conditions about
      driving generally falls to health care providers, who are often not neurologists.
      Three hundred thirty-five consecutive charts of patients discharged from our
      Emergency Department were retrospectively reviewed by diagnosis codes associated
      with altered consciousness. A total of 267 patients met our inclusion criteria,
      of whom 27 (10.1%) were counseled regarding driving--by the Emergency Department
      physician and/or consulting neurologist. Although the counseling rate for driving
      was 10/29 (34.5%) when a neurologist was involved, it was found to be only 17/238
      (7.1%) when neurological services were not sought. Patients presenting with
      seizure were more likely to be counseled than those presenting with other
      episodes of loss of consciousness. Accurate knowledge of driving laws by health
      care workers and patients has the potential to minimize liability and improve
      public safety and quality of care.

PMID- 19162228
TI  - What is it like to receive a diagnosis of nonepileptic seizures?
AB  - The aim of this qualitative study was to provide insight into the experience of
      receiving the diagnosis of nonepileptic seizures (NES) from the patient's
      perspective. Semistructured interviews were conducted with eight patients who had
      received the diagnosis of NES over the preceding 6 months. All participants were
      on a waiting list for psychological treatment. Verbatim records of the interviews
      were analyzed using interpretative phenomenological analysis (IPA). Six main
      themes emerged from the data ("the experience of living with nonepileptic
      seizures", "label and understanding", "being left in limbo land", "doubt and
      certainty", "feeling like a human being again", and "emotional impact of
      diagnosis"). An ability to integrate the diagnosis into a personal narrative was
      key to participants' acceptance of the diagnosis. The communication of the
      diagnosis left some participants feeling distressed. The results suggest that
      patients need more time and resources to understand the diagnosis and more
      support after they have received it.

PMID- 19162229
TI  - Effectiveness and tolerability of rufinamide in children and adults with
      refractory epilepsy: first European experience.
AB  - OBJECTIVE: The aim of the study was to explore the effectiveness and tolerability
      of rufinamide in a heterogeneous group of patients with refractory epilepsies in
      Europe, immediately after the drug became available as an orphan drug for the
      adjunctive treatment of Lennox-Gastaut syndrome (LGS). METHODS: This
      observational study was conducted as a collection of retrospective data from
      multiple centers in Germany and Austria. Clinical course in patients treated with
      rufinamide was documented. Initial dosage and titration schedule of rufinamide
      were at the discretion of the treating physician according to medical need. The
      observation period was 12 weeks. Effectiveness was evaluated by comparing the
      frequency of seizures with limitations to the countability between baseline and
      the last 4-week period of observation. RESULTS: The study population consisted of
      45 children and 15 adults (mean age: 14.5+/-11.6 years, range: 1-50) with various
      severe and inadequately controlled epilepsy syndromes, that is, LGS (n=31),
      idiopathic generalized epilepsy syndromes (n=5), cryptogenic unclassified
      generalized epilepsy (n=7), and partial epilepsy (n=17). The response rate (50%
      reduction in countable seizures) was 46.7% (28 of 60 patients) in total; 25.0%
      experienced a 75% reduction in seizure frequency and 21.7% experienced a 50-75%
      reduction. Complete seizure control was achieved by 8.3%. The highest response
      rate was observed in patients with LGS (17/31, 54.8%), and the lowest in patients
      with partial epilepsy (4/17, 23.5%). Response rate in patients with unclassified
      generalized epilepsy was 42.8% (3/7 patients). A total of 67 adverse events were
      reported by 35 of 60 patients. The most frequently occurring adverse events were
      fatigue (18.3%), vomiting (13.3%), and loss of appetite (10.0%). No serious
      adverse events were observed. CONCLUSIONS: These preliminary data suggest that
      rufinamide may be effective and well tolerated in the treatment of children and
      adults with various epilepsy syndromes and difficult-to-control seizures. The
      results of our study suggest that the efficacy of rufinamide in patients with
      generalized epilepsy might be comparable to that in patients with LGS, whereas
      rufinamide was less effective in patients with partial epilepsy.

PMID- 19162230
TI  - Topiramate in patients with epilepsy and intellectual disability.
AB  - This noninterventional single-arm study explored effectiveness and behavioral
      outcomes in intellectually disabled patients treated with topiramate for
      epilepsy. Data from 21 patients diagnosed with cerebral palsy were available for
      evaluation. Behavioral changes were assessed using the validated Aberrant
      Behavior Checklist and Matson Evaluation of Social Skills for Individuals with
      Severe Retardation (MESSIER) scales. Some improvement in nearly all behavioral
      aspects was observed under concomitant topiramate therapy; for example, the
      Aberrant Behavior Checklist total score changed from 33.7+/-25.8 to 25.3+/-19.1
      (P=0.047). In addition, seizure frequency decreased from 16.1+/-22.2/4 weeks to
      12.2+/-17.0/4 weeks (N=21, P=0.164). Fifty-two percent of the patients
      experienced at least 50% seizure reduction during the 24-week treatment period.
      The safety profile is in accordance with the current Summary of Product
      Characteristics of Topiramate. Two unexpected deaths were attributed to sudden
      unexpected death in epilepsy.

PMID- 19162231
TI  - Focal epileptic seizures mimicking sleep paralysis.
AB  - Sleep paralysis (SP) is a common parasomnia. The diagnostic criteria for SP, as
      reported in the International Classification of Sleep Disorders, are essentially
      clinical, as electroencephalography (EEG)-polysomnography (PSG) is not mandatory.
      We describe a subject whose sleep-related events fulfilled the diagnostic
      criteria for SP, even though her visual hallucinations were elementary,
      repetitive and stereotyped, thus differing from those usually reported by
      patients with SP. Video/EEG-PSG documented the focal epileptic nature of the SP
      like episodes.

PMID- 19162232
TI  - Improving accuracy for identifying related PubMed queries by an integrated
      approach.
AB  - PubMed is the most widely used tool for searching biomedical literature online.
      As with many other online search tools, a user often types a series of multiple
      related queries before retrieving satisfactory results to fulfill a single
      information need. Meanwhile, it is also a common phenomenon to see a user type
      queries on unrelated topics in a single session. In order to study PubMed users'
      search strategies, it is necessary to be able to automatically separate unrelated
      queries and group together related queries. Here, we report a novel approach
      combining both lexical and contextual analyses for segmenting PubMed query
      sessions and identifying related queries and compare its performance with the
      previous approach based solely on concept mapping. We experimented with our
      integrated approach on sample data consisting of 1539 pairs of consecutive user
      queries in 351 user sessions. The prediction results of 1396 pairs agreed with
      the gold-standard annotations, achieving an overall accuracy of 90.7%. This
      demonstrates that our approach is significantly better than the previously
      published method. By applying this approach to a one day query log of PubMed, we
      found that a significant proportion of information needs involved more than one
      PubMed query, and that most of the consecutive queries for the same information
      need are lexically related. Finally, the proposed PubMed distance is shown to be
      an accurate and meaningful measure for determining the contextual similarity
      between biological terms. The integrated approach can play a critical role in
      handling real-world PubMed query log data as is demonstrated in our experiments.

PMID- 19162233
TI  - Applying evolutionary terminology auditing to the Gene Ontology.
AB  - Evolutionary Terminology Auditing (ETA) is a novel way to assess the quality of
      terminologies using reality as benchmark. The key idea is that terms added to
      each new version of a terminology reflect unjustified absences and terms that are
      deleted unjustified presences in previous versions of the terminology. The method
      requires that terminology authors not only keep track of changes in successive
      versions, but also motivate the changes introduced. In this paper, we report on
      how our method has been applied to the Gene Ontology (GO), a collection of three
      structured, controlled vocabularies for use in annotating genes, gene products
      and sequences. We demonstrate that even where the basic requirements for its
      application are only partially satisfied, the approach can still yield results
      which are useful for quantifying and forecasting the evolution of a terminology's
      quality over time.

PMID- 19162234
TI  - A neural network-based biomarker association information extraction approach for
      cancer classification.
AB  - A number of different approaches based on high-throughput data have been
      developed for cancer classification. However, these methods often ignore the
      underlying correlation between the expression levels of different biomarkers
      which are related to cancer. From a biological viewpoint, the modeling of these
      abnormal associations between biomarkers will play an important role in cancer
      classification. In this paper, we propose an approach based on the concept of
      Biomarker Association Networks (BAN) for cancer classification. The BAN is
      modeled as a neural network, which can capture the associations between the
      biomarkers by minimizing an energy function. Based on the BAN, a new cancer
      classification approach is developed. We validate the proposed approach on four
      publicly available biomarker expression datasets. The derived Biomarker
      Association Networks are observed to be significantly different for different
      cancer classes, which help reveal the underlying deviant biomarker association
      patterns responsible for different cancer types. Extensive comparisons show the
      superior performance of the BAN-based classification approach over several
      conventional classification methods.

PMID- 19162235
TI  - Effects of liver biopsy sample length and number of readings on sampling
      variability in nonalcoholic Fatty liver disease.
AB  - BACKGROUND & AIMS: Liver biopsy is required to diagnose nonalcoholic
      steatohepatitis (NASH) in patients with suspected non-alcoholic fatty liver
      disease (NAFLD); recent studies suggested significant sampling variability. Using
      percutaneous liver biopsy samples from patients with suspected NAFLD, we examined
      the relationship between histological yield and length of biopsies, number of
      cores and number of independent readings. METHODS: Three cores of liver tissue
      were collected, by percutaneous liver biopsy, from each of 50 patients suspected
      to have NAFLD. The diagnostic yield (percent with definite NASH) and other
      histological findings from 2 independent, blinded examinations of 2 cores and
      from all 3 cores combined were assessed. RESULTS: Steatosis, lobular inflammation
      and fibrosis scores were significantly higher when 3 samples were analyzed,
      compared with 2. However, between groups, there were no significant differences
      in hepatocyte ballooning, proportion with an NAFLD activity score > or =4 or
      proportion with definite NASH (57% vs 61%, P = .3). The length of the biopsy
      sample correlated with percentage of patients found to have definite NASH (29%,
      46%, 56%, and 65% in biopsies measuring <10 mm, 10-14 mm, 15-24 mm, and > or =25
      mm, respectively; P < .0001). When biopsy specimens were read twice by the same
      pathologist, the composite of the 2 independent readings yielded a significantly
      higher yield for several histological features, compared with the first reading.
      CONCLUSIONS: There is a significant relationship between histological yield and
      sample length and number of independent readings of liver biopsy samples. More
      studies are needed to optimize the strategy for liver biopsy, to more effectively
      assess histology in patients with suspected NAFLD.

PMID- 19162236
TI  - Prevalence of eosinophilic esophagitis in an adult population undergoing upper
      endoscopy: a prospective study.
AB  - BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is characterized by
      eosinophilic infiltration of the esophagus. The purpose of this prospective study
      was to determine the prevalence and clinical predictors of EoE in patients
      undergoing elective upper endoscopy. METHODS: We enrolled 400 consecutive adults
      (median age, 50 years; range, 19-92 years) who underwent routine upper endoscopy
      from March to September 2007 at a tertiary care military hospital. All patients
      completed a symptom questionnaire. All endoscopic findings were noted. Eight
      biopsies were obtained from proximal and distal esophagus and were reviewed by a
      blinded gastrointestinal pathologist. Patients had EoE if > or =20
      eosinophils/high-power field were present. RESULTS: The prevalence of EoE in this
      cohort was 6.5% (25/385; 95% confidence interval, 4.3%-9.4%). Compared with EoE
      negative patients, EoE positive patients were more likely to be male (80.0% vs
      48.1%, P = .003), younger than 50 years (72.0% vs 48.9%, P = .037), and have
      asthma (32.0% vs 10.8%, P = .006), a food impaction (32.0% vs 8.9%, P = .002),
      dysphagia (64.0% vs 38.1%, P = .018), and classic endoscopic findings (rings,
      furrows, plaques, or strictures) of EoE (all P < .01). Logistic regression
      identified asthma (odds ratio [OR], 4.48), male gender (OR, 4.23), and esophageal
      rings (OR, 13.1) as independent predictors of EoE. The presence of classic
      endoscopic findings of EoE had a sensitivity of 72% (54%-88%), specificity of 89%
      (87%-90%), and negative predictive value of 98% (95.6%-99.1%). CONCLUSIONS: The
      prevalence of EoE in an outpatient population undergoing upper endoscopy was
      6.5%. The characteristic findings of EoE patients included male gender, history
      of asthma, and the presence of classic findings of EoE on endoscopy, which is the
      strongest predictor of this disease process.

PMID- 19162237
TI  - Congenital Chagas disease involves Trypanosoma cruzi sub-lineage IId in the
      northwestern province of Salta, Argentina.
AB  - Trypanosoma cruzi is genetically classified into six discrete phylogenetic
      lineages on the basis of different genetic markers. Identifying lineages
      circulating among humans in different areas is essential to understand the
      molecular epidemiology of Chagas disease. In the present study, 18 T. cruzi
      isolates from congenitally infected newborns in the northwestern province of
      Salta-Argentina were studied by multilocus enzyme electrophoresis (MLEE) and
      random amplified polymorphic DNA (RAPD). All isolates were typed by MLEE and RAPD
      as belonging to T. cruzi IId. Analysis of minor variants of TcIId using probes
      hybridizing with hypervariable domains of kDNA minicircles, detected three
      variants with a similar distribution among the isolates. Our findings confirm the
      presence of T. cruzi IId among congenitally infected newborns in northwestern
      Argentina and support the assumption that human infection by T. cruzi in the
      Southern Cone countries of Latin America is due principally to T. cruzi II.

PMID- 19162238
TI  - Dermatophagoides farinae extract induces severe atopic dermatitis in NC/Nga mice,
      which is effectively suppressed by the administration of tacrolimus ointment.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease, which is
      accompanied by marked increases in the levels of inflammatory cells, including
      mast cells and eosinophils as well as T cells and macrophages. To investigate the
      expression pattern of chemokines in AD, a house dust mite, Dermatophagoides
      farinae extracts (DfE)-induced NC/Nga AD model was developed in mice, and this
      model was used to determine the expression levels of chemokines in atopic lesions
      using DNA microarrays and RT-PCR. When NC/Nga mice were repeatedly treated with
      DfE for 4 to 7 weeks on the back skin, the mRNA expression levels of CCL20/LARC,
      CCL24/eotaxin-2, CCL17/TARC, and CCL11/eotaxin-1 were markedly induced and lesser
      of CCL2/MCP-1, within the inflammatory lesion of the back skin.
      Immunohistochemical staining revealed the expression of these chemokines in the
      epidermis and dermis of DfE-treated NC/Nga mice. Interestingly, repeated
      application of tacrolimus ointment potently inhibited DfE-induced atopic
      dermatitis in NC/Nga mice concomitant with the inhibition of these changes in
      chemokine gene and protein expression levels particularly of CCL20/LARC,
      CCL17/TARC, and CCL11/eotaxin-1. These data indicate that severe atopic
      dermatitis induced by DfE accompanies elevated chemokine levels, and it was
      proposed that tacrolimus ointment is beneficial for the treatment of severe AD.

PMID- 19162240
TI  - The mechanisms on apoptosis by inhibiting VEGF expression in human breast cancer
      cells.
AB  - This study investigated apoptotic mechanisms of down-expression vascular
      endothelial growth factor (VEGF) by short interfering RNA (siRNA) in human breast
      cancer MCF-7 cells. Human breast cancer cells were evaluated for the expression
      of VEGF and VEGF receptor 2 (VEGFR-2). siRNA targeting VEGF mRNA were chemically
      synthesized and transfected into cells with Lipofectamine2000. In vitro
      assessments were then made of the ability of anti-VEGF siRNA to knock down
      expression of VEGF and the subsequent effect this decreased expression had on
      breast cancer cell apoptosis. Growth curve construction and nude mice
      experimentation in vivo were performed to assess the effects of VEGF silencing on
      tumor growth. Those cells transfected with siRNA targeting VEGF showed a 65%
      knockdown in VEGF expression and a marked increase in cell apoptosis. The
      expression of Bcl-2 protein in MCF-7 cells was decreased, the level of Bax
      protein was kept the same, cytochrome c was released from mitochondria into
      cytosol, and the cleaved Caspase-3 protein rose after siRNA transfection. The
      siRNA targeting human VEGF could induce apoptosis in MCF-7 cells and the
      mechanism of apoptosis is possibly related with changing Bcl-2/Bax expression
      ratio, releasing cytochrome c from mitochondria into cytosol, and up-regulation
      of Caspase-3 protein, but also could suppress the growth of breast cancer cells
      in vivo. VEGF might be a potential therapeutic target for human breast cancer.

PMID- 19162241
TI  - Signaling mechanisms of angiotensin II in regulating vascular senescence.
AB  - Angiotensin (Ang) II, the major effector of the rennin-angiotensin-aldosterone
      system (RAAS), has multiple functions in regulating cardiovascular hemodynamics
      and structure. Recent evidence strongly supports that Ang II promotes the onset
      and progression of vascular senescence, which is associated with vascular
      functional and structural changes, contributing to age-related vascular diseases.
      The vast majority of the cardiovascular actions of Ang II, including vascular
      senescence, are mediated by the Ang II type-1 (AT(1)) receptor. Similar to its
      growth-promoting process, the signaling mechanisms of AT(1) receptor-mediated
      vascular senescence-promoting effects involve activation of small G-protein Ras
      such as Ki-ras2A, mitogen-activated protein kinases (MAPK) such as extracellular
      signal-regulated kinase 1/2, and transcription factors including nuclear factor
      (NF)-kappaB and activator protein (AP)-1, and increased generation of reactive
      oxygen species. Moreover, AT(1) receptor stimulation has been suggested to
      inactivate cyclin-dependent kinase complexes by up-regulation of cell cycle
      regulators such as p53 and p21, resulting in cellular senescence. Furthermore,
      the interaction between Ang II and aldosterone (Aldo) in their contribution to
      cardiovascular pathophysiology has been highlighted. Aldo can interact with Ang
      II signaling via a genomic mechanism mediated by the mineralocorticoid receptor
      (MR). Aldo via MR couples with the AT(1) receptor to elicit the Ras/NF-kappaB, AP
      1/p53/p21 pathway involving oxidative stress, leading to synergistic promotion of
      vascular senescence. Although the precise mechanisms controlling cellular
      senescence are currently poorly understood, this article reviews recent findings
      on the signaling mechanisms elicited by RAAS from the perspective of AT(1)
      receptor blockers and/or MR blockers in the treatment of age-related vascular
      diseases.

PMID- 19162239
TI  - Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro.
AB  - Bromelain (Br), an extract from pineapple stem with cysteine protease activity,
      exerts anti-inflammatory effects in a number of inflammatory models. We have
      previously shown that Br treatment decreased activated CD4(+) T cells and has a
      therapeutic role in an ovalbumin-induced murine model of allergic airway disease.
      The current study was designed to determine the effect of Br on CD4(+) T cell
      activation, specifically the expression of CD25 in vitro. CD25 is up regulated
      upon T cell activation, found as a soluble fraction (sCD25) and is a therapeutic
      target in inflammation, autoimmunity and allergy. Br treatment of anti-CD3
      stimulated CD4(+) T cells reduced CD25 expression in a dose and time dependent
      manner. This reduction of CD25 was dependent on the proteolytic action of Br as
      the addition of E64 (a cysteine protease inhibitor) abrogated this response. The
      concentration of sCD25 was increased in supernatants of Br treated activated
      CD4(+) T cells as compared to control cells, suggesting that Br proteolytically
      cleaved cell-surface CD25. This novel mechanism of action identifies how Br may
      exert its therapeutic benefits in inflammatory conditions.

PMID- 19162242
TI  - Mast cells and histamine metabolism in skin lesions from MRL/MP-lpr/lpr mice.
AB  - It is likely that mast cell and histamine metabolism are involved in autoimmune
      tissue injury such as cutaneous lupus erythematosus (LE) because different
      histamine receptors can regulate Th1 and Th2 cells. In order to verify the role
      of the axis of mast cell-histamine metabolism-histamine receptor, the autoimmune
      mouse has been investigated. The MRL/Mp-lpr/lpr (MRL/lpr) mouse is a good model
      for the spontaneous development of skin lesions similar to those seen in human
      LE. In skin lesions from MRL/l mice, there are many infiltrating T cells and mast
      cells in the dermis and impaired histamine metabolism, in which the low activity
      of histamine-N-methyltransferase and the related prolonged effects of histamine
      in the skin tissue seem to play a definite pathological role in the development
      of spontaneous lupus-like eruptions. The expression of H2R on the mast cell
      decreases within these skin lesions at 5 months of age. It is interesting that
      the activity of HMT runs in parallel with the expression of H2R over the time
      course of the skin changes in MRL/l mice, but the relationship between these two
      observations remains obscure. The accumulation of mast cells expressing H2R and
      prolonged effects of histamine may occur to regulate the production of Th1 and
      Th2 cytokines in the skin lesions of MRL/l mice.

PMID- 19162243
TI  - Histologic features of cutaneous lupus erythematosus.
AB  - Histologic examination of lesions plays a key role in the diagnostics of
      cutaneous lupus erythematosus (LE). LE has a broad spectrum of histopathological
      signs, which are related to the stages of the lesions. In addition to the main
      subtypes of LE, we report on special manifestations like Rowell's-syndrome and
      Chilblain LE, and give an account of Kikuchi-Fujimoto disease (histiocytic
      necrotizing lymphadenitis), which may be associated with systemic LE. Furthermore
      the most considerable histopathologic differential diagnoses are discussed.

PMID- 19162244
TI  - The 100th anniversary of lupus erythematosus tumidus.
AB  - In 1909, the term "lupus erythematodes tumidus" was first introduced by the
      German Dermatologist E. Hoffmann. The next case reports of lupus erythematosus
      tumidus (LET) were not described until 1930, and in the following years, only a
      few further cases were reported. This might have been due to the fact that
      authors have not considered LET as a separate entity different from other
      variants of cutaneous lupus erythematosus (CLE), and it is likely that skin
      lesions described under different designations represent the same disease entity.
      Therefore, LET has been underestimated and neglected in the literature and has
      been characterized by clinical, histopathological, and immunohistochemical
      features only in recent years. In particular, phototesting has been crucial in
      defining LET as a very photosensitive entity of CLE. Up to now, more than 40
      reports of LET have been published demonstrating that the course and prognosis of
      LET are generally more favorable than in other subtypes of CLE. A new
      classification system, including LET as the intermittent subtype of CLE (ICLE)
      has been suggested. On the occasion of the 100th anniversary of the first
      description of LET, we have reviewed the literature and provide here an overview
      on the different aspects of the disease.

PMID- 19162245
TI  - Neonatal lupus erythematosus in Japan: a review of the literature.
AB  - Neonatal lupus erythematosus (NLE) is an autoimmune disease associated with
      maternal anti-SS-A/Ro and anti-SS-B/La antibodies. NLE is characterized by
      cutaneous erythema, congenital heart block (CHB), hepatic dysfunction and
      hematological abnormalities. CHB is irreversible, usually requiring a pacemaker,
      but other symptoms are reversible and most disappear within 6 months in parallel
      with declining antibody levels. In Japan, 193 cases of NLE were reported between
      1971 and 2008. Most showed erythema, and only 23% of cases presented with CHB.
      Conversely, antibody status had not been examined in many infants presenting with
      CHB during the same period. Most pregnant woman with anti-SS-A/Ro and anti-SS
      B/La antibodies are asymptomatic, and antibody status is first indicated when
      their child shows symptoms of NLE. These women show a greater risk of delivering
      an infant with CHB than normal. CHB is important because the main morbidity and
      mortality of NLE is from CHB. All clinicians should be familiar with the
      characteristics of NLE. We believe all pregnant women should be screened for anti
      SS-A/Ro and anti-SS-B/La antibodies.

PMID- 19162246
TI  - New impacts of cutaneous lupus erythematosus for global standard concepts.
      Preface.

PMID- 19162247
TI  - Hair follicle stem cells in the pathogenesis of the scarring process in cutaneous
      lupus erythematosus.
AB  - Lupus erythematosus (LE) is an autoimmune disease that can affect one or more
      internal organs (systemic LE [SLE]) as well as the skin (CLE). Common cutaneous
      subtypes of CLE are chronic CLE (CCLE) and subacute CLE (SCLE). CCLE is the only
      type of CLE which heals with scarring and this may affect any site in the body.
      The fact that inflammation in CCLE generally involves the bulge area of the
      follicles (where the stem cells reside) raises the possibility that damage to the
      stem cells may be one process leading to permanent loss of follicles. One of the
      most useful distinctive markers of the stem cells is cytokeratin 15 (CK15) and
      this has been used in some studies to demonstrate the involvement of the bulge
      region in the scarring process in primary cicatricial alopecia and DLE. The bulge
      region appears to be involved in the scarring process in CLE and other types of
      cicatricial alopecia as part of broader involvement of the hair follicles; it is
      secondarily affected by the surrounding inflammatory cell infiltrate. Expression
      of the stem cell marker CK15 diminished and was then absent indicating either
      damage to stem cells or differentiation to help in the repair process.

PMID- 19162248
TI  - Clinical entity of Lupus erythematosus panniculitis/lupus erythematosus
      profundus.
AB  - We reviewed the clinical and histological characteristics of the 44 cases of
      lupus erythematosus profundus (LEP) that have been encountered in our department.
      The female to male ratio was 4.5:1. The mean age of the females was 36 years, and
      the mean age of the males was 34 years. The most common sites were the face
      (38.4%) and upper limbs (26.0%). Even among the patients with LEP alone many of
      the positive patients had low antibody titers of 1:40 or 1:80. In 18 of the 44
      cases SLE was complicated by LEP, and in those cases there was a tendency for LEP
      to develop during the course of SLE (11 cases). The important histological
      findings were lobular panniculitis associated with mucin deposition (32 cases)
      and a tendency to be associated with damage to the basal cell layer. In addition,
      the direct immunofluorescence test was positive in both the basement membrane
      (90.5%) and blood vessels (85.7%) in a high percentage of even the cases of LEP
      alone. Based on the above findings, LEP is a cutaneous variant of erythematosus,
      and the importance of the histological findings when making the diagnosis of LEP
      was reconfirmed.

PMID- 19162249
TI  - Classification of lupus erythematosus based upon Japanese patients.
AB  - The two dimensional classification system for lupus erythematosus (LE) is
      proposed. The terms for diagnoses and those for eruptions should be used
      separately. The terms for diagnoses are cutaneous-limited LE (CLE), intermediate
      LE (ILE) and systemic LE (SLE). CLE is an entity which has only cutaneous
      manifestations, and ILE has mild systemic manifestations. On the other hand, the
      terms for skin manifestations are chronic cutaneous LE (CCLE), subacute cutaneous
      LE (SCLE) and acute cutaneous LE (ACLE). CCLE includes discoid LE (DLE),
      chilblain LE and LE profundus. SCLE includes annular SCLE and papulosquamous
      SCLE. In this classification system, the condition of each LE patient is
      estimated integratedly both in systemic and cutaneous standpoints. Analyzing
      Japanese LE patients by this classification system, the usefulness of this system
      and the features of Japanese LE patients are discussed.

PMID- 19162250
TI  - The role of innate immune responses in autoimmune disease development.
AB  - Autoimmune diseases are systemic or organ-specific disorders that are the result
      of an attack of the immune system against the body's own tissue. Development of
      autoimmune disease is generally avoided by distinct mechanisms that silence
      adaptive self-reactive T or B cells. The innate immune system is critically
      involved in the defense against pathogens and the induction of primary adaptive
      immune responses. Toll-like receptors (TLRs) are key receptors that activate the
      innate immunity in response to pathogen recognition. Recent data show that
      activation of innate immune cells such as dendritic cells (DCs) can break this
      state of tolerance and induce autoimmunity by priming autoreactive T cells. Here
      we review recent examples of how innate immune responses influence the adaptive
      immunity in the induction or regulation of autoimmune disease.

PMID- 19162251
TI  - Studies of interaction of homo-dimeric ferredoxin-NAD(P)+ oxidoreductases of
      Bacillus subtilis and Rhodopseudomonas palustris, that are closely related to
      thioredoxin reductases in amino acid sequence, with ferredoxins and pyridine
      nucleotide coenzymes.
AB  - Ferredoxin-NADP(+) oxidoreductases (FNRs) of Bacillus subtilis (YumC) and
      Rhodopseudomonas palustris CGA009 (RPA3954) belong to a novel homo-dimeric type
      of FNR with high amino acid sequence homology to NADPH-thioredoxin reductases.
      These FNRs were purified from expression constructs in Escherichia coli cells,
      and their steady-state reactions with [2Fe-2S] type ferredoxins (Fds) from
      spinach and R. palustris, [4Fe-4S] type Fd from B. subtilis, NAD(P)(+)/NAD(P)H
      and ferricyanide were studied. From the K(m) and k(cat) values for the diaphorase
      activity with ferricyanide, it is demonstrated that both FNRs are far more
      specific for NADPH than for NADH. The UV-visible spectral changes induced by
      NADP(+) and B. subtilis Fd indicated that both FNRs form a ternary complex with
      NADP(+) and Fd, and that each of the two ligands decreases the affinities of the
      others. The steady-state kinetics of NADPH-cytochrome c reduction activity of
      YumC is consistent with formation of a ternary complex of NADPH and Fd during
      catalysis. These results indicate that despite their low sequence homology to
      other FNRs, these enzymes possess high FNR activity but with measurable
      differences in affinity for different types of Fds as compared to other more
      conventional FNRs.

PMID- 19162252
TI  - Resistance of bromelain to SDS binding.
AB  - Interaction of the plant cysteine protease bromelain with SDS has been studied
      using CD spectroscopy, intrinsic fluorescence emission, extrinsic fluorescence
      probe pyrene, isothermal calorimetric (ITC) investigations and inhibition of
      hydrolyzing activity. Results exhibit number of synchronous transitions when
      plotted against the total SDS concentration. SDS at submicellar level caused
      conformation change of bromelain leading to a stable entity. ITC and pyrene
      experiments suggest that the structural modifications below 5 mM, the cmc(app) of
      SDS solutions containing bromelain, are the result of alterations of solvent
      hydrophobicity or non-specific weak binding and/or adsorption of SDS monomers.
      Melting temperature (T(m)) and the free energy change for thermal unfolding
      (DeltaG(unf)) of the SDS induced conformers was decreased by 5 degrees C and 0.5
      kcal/mol respectively, compared to native bromelain. Below 5 mM, SDS caused large
      decrease in V(max) without affecting K(m) for the substrate Z-Arg-Arg-NHMec.
      Analysis of kinetic data imply that SDS acts as a partial non-competitive
      inhibitor since even at 100 mM, the residual activity of bromelain was retained
      by 3%. Inhibition studies show an IC(50) of 0.55 mM and a high K(i) of 0.145 mM.
      These demonstrate that bromelain is resistant to SDS binding and denaturation, a
      property known for beta-sheet rich kinetically stable proteins.

PMID- 19162253
TI  - Human monoclonal ScFv neutralize lethal Thai cobra, Naja kaouthia, neurotoxin.
AB  - Animal derived anti-Naja. kaouthia (Thai cobra) venom is used for specific
      treatment of the snake bitten victims. Many recipients develop allergic reaction
      or anti-isotype response which causes serum sickness. A better therapeutic
      antibody is needed. In this study, long alpha-neurotoxin was purified from the N.
      kaouthia holovenom and verified by 2D-LC/MS-MS. The toxin was used as antigen in
      a phage bio-panning to select phage clones displaying human single chain variable
      antibody fragments (HuScFv) from a phage display antibody library constructed
      from immunoglobulin genes of non-immunized Thai blood donors. HuScFv that
      specifically bound to the neurotoxin were produced from huscfv-phagemid
      transformed E. coli clones and affinity purified. The HuScFv could neutralize
      toxicity of the N. kaouthia neurotoxin and rescued the envenomized mice from the
      neurotoxin mediated lethality. Peptide mimotope of the neutralizing HuScFv
      matched with an amino acid sequence (epitope) located in the loop-3 of the N.
      kaouthia long alpha-neurotoxin which functions in acetylcholine receptor binding.
      The mimotope is also similar to peptide sequences found on other snake venom
      neurotoxins implying a possibility of the HuScFv to exert pan-neutralizing
      activity against multiple snake neurotoxins.

PMID- 19162254
TI  - Predictive value of femoral head heterogeneity for fracture risk.
AB  - Osteoporosis (OP) is characterized by low bone mass and weak bone structure,
      which results in increased fracture risk. It has been suggested that osteoporotic
      bone is strongly adapted to the main loading direction and less adapted to the
      other directions. In this study, we hypothesized that osteoporotic femoral heads
      have 1) an increased anisotropy; 2) a more heterogenic distribution of bone
      volume fraction (BV/TV) throughout the femoral head; and, 3) a more heterogenic
      distribution of the trabecular thickness (Tb.Th.) throughout the femoral head, as
      compared to non-osteoporotic bone. To test these hypotheses, we used 7
      osteoporotic femoral heads from patients who fractured their femoral neck and 7
      non-fractured femoral heads from patients with osteoarthrosis (OA). Bone
      structural parameters from the entire trabecular region were analyzed using
      microCT. We found that the degree of anisotropy was higher in the fractured
      femoral heads, i.e. 1.72, compared to a value of 1.61 in the non-fractured
      femoral heads. The BV/TV and Tb.Th. and their variations throughout the femoral
      head, however, were all significantly lower in the fractured group. Hence, the
      first hypothesis was confirmed, whereas the other two were rejected.
      Interestingly, the variation of Tb.Th. throughout the femoral head provided a
      100% discrimination between the OP and OA groups, i.e. for the same BV/TV, all
      fractured cases had a less heterogenic distribution. In conclusion, our results
      suggest that bone loss in OP takes place uniformly throughout the femoral head,
      leading to an overall decrease in bone mass and trabecular thickness.
      Furthermore, the variation of Tb.Th. in the femoral head could be an interesting
      parameter to improve the prediction of fracture risk in the proximal femur.

PMID- 19162255
TI  - Age of acquisition affects early orthographic processing during Chinese character
      recognition.
AB  - Three experiments investigated age of acquisition (AoA) effects on early
      orthographic processing during Chinese character recognition. In Experiment 1, we
      measured the accuracy of identification of brief masked characters, accuracy was
      higher for early compared to late acquired characters. In Experiment 2, the
      visual duration threshold (VDT) was measured for both early and late acquired
      Chinese characters. The results showed that early acquired characters were
      successfully identified at shorter display durations than late acquired
      characters. Significant AoA effects were also found in Experiment 3, using a
      lexical decision task requiring mainly orthographic processing (discriminating
      real Chinese characters from orthographically illegal and unpronounceable
      characters). In summary, three experiments provide converging empirical evidence,
      for AoA effects on the early orthographic processing stages of Chinese character
      recognition. These results suggest that AoA effects during word identification go
      beyond the phonological or semantic processing stages. These results aslo provide
      cross-linguistic evidence for an AoA effect on early perceptual processing during
      identification.

PMID- 19162256
TI  - Quest for ion-ion correlations in electric double layers and overcharging
      phenomena.
AB  - A discussion is given of the experimental evidence for overcharging, also known
      as charge reversal. The phenomenon is very common. The most general explanation
      is specific chemical adsorption. However, overcharging can also be explained on
      the basis of ion-ion correlations, which is rather a physical type of
      interpretation, and which can also be specific. Several theories have been
      developed for that. So, there is the luxury problem that two alternative
      explanations are available for the same observation. The purpose of this paper is
      to consider the various approaches critically and try to devise experimental
      options to discriminate between the two interpretations.

PMID- 19162257
TI  - Etiologic discussion and clinical relevance of thyroid ultrasonography in
      subclinical hypothyroidism. A retrospective study in 1845 patients.
AB  - BACKGROUND: Acquired subclinical hypothyroidism in adulthood is mainly due to
      autoimmune thyroiditis. In the absence of a goiter or a palpable firm thyroid,
      measurement of thyroid antibodies can improve the diagnosis. Whether thyroid
      antibodies are detected or not, what might be the clinical relevance of
      ultrasonography in this setting? METHODS: We studied 1845 cases of subclinical
      hypothyroidism in adults recruited for symptoms indicative of hypothyroidism or
      thyroid pathology. All patients were screened for thyroid antibodies and
      underwent an ultrasonographic thyroid examination. LOCALISATION: Multicentric
      retrospective study. RESULTS: Chronic autoimmune thyroiditis was confirmed in 70%
      of patients. Thyroid antibodies were undetectable in 30% of patients. In all
      patients, thyroid ultrasound facilitated measurement of the thyroid volume and
      detection of non-palpable nodules and therefore allowed biopsy. In patients
      negative for thyroid antibodies, ultrasonography suggested autoimmune thyroiditis
      in 31% of cases. Ultrasonography did not contribute to diagnosis in a large
      number of patients without nodules and in case of normal echostructure. The
      strategy of thyroid hormone replacement therapy was not influenced by
      ultrasonographic data. Thyroid biopsies detected smears suspected to be cancerous
      in 10 patients (4%). Cancer was confirmed in nine patients after surgery.
      Ultrasonography displayed suspicious aspects in six patients. CONCLUSION: In
      subclinical hypothyroidism, thyroid ultrasonography is not required for the
      diagnosis of autoimmune thyroiditis but is useful for patients with abnormal
      thyroid palpation and allows detection of non-palpable thyroid nodules. For
      patients that were negative for thyroid antibodies, thyroid ultrasonography can
      improve diagnosis for some patients, allowing detection of autoimmune
      thyroiditis.

PMID- 19162258
TI  - Shoulder strength of females while sitting and standing as a function of hand
      location and force direction.
AB  - This study evaluated single-handed isometric push strength capabilities of
      females working at or above-shoulder level. We examined the influence of force
      exertion direction (vertical, horizontal and lateral), angle of shoulder flexion
      from horizontal (0 degrees, 30 degrees, 60 degrees and 90 degrees) and gross body
      posture (standing and sitting), on maximal volitional shoulder strength. Force
      exertion direction had the greatest affect on shoulder strength (p<0.0001).
      Strength was greatest in the vertical axis pushing downwards and weakest in the
      horizontal plane pushing forwards. Angle influenced shoulder strength when
      considered together with direction (p<0.0001). However, these effects were
      dominated by direction results. Marginal differences in strength existed between
      sitting and standing (p>0.05). These results can be used to design workspaces
      that consider individual strength limitations and their dependence on force
      direction, work orientation, and gross body posture.

PMID- 19162259
TI  - Angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II
      type 1 receptor (AT1R) gene polymorphisms in generalized aggressive
      periodontitis.
AB  - AIM: Host response to periodontopathic microorganisms can be modulated by genetic
      factors. Accumulated evidence highlighted the role of renin-angiotensin system
      (RAS) in inflammatory response thus potential implication of this molecular
      system in the pathogenesis of periodontitis can be suggested. The present study
      investigated common genetic variants of molecules within the RAS family namely
      angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II
      type 1 receptor (AT1R) in relation to generalized aggressive periodontitis (G
      AgP). METHODS: DNA was obtained from peripheral blood of 103 G-AgP patients and
      100 periodontally healthy subjects. ACE I/D, AGT M235T and AT1R A1166C
      polymorphisms were genotyped by polymerase chain reaction and restriction
      fragment length polymorphism method. Chi-square, ANOVA and logistic regression
      were used in statistical analyses. RESULTS: Both ACE I/D and AT1R polymorphisms
      were similar in G-AgP and healthy groups (p>0.05). G-AgP subjects exhibited
      decreased AGT TT genotype and T allele frequency as compared to healthy subjects
      (p<0.05). The same trend was also observed in the nonsmoker subgroup regarding
      investigated RAS polymorphisms. CONCLUSIONS: Present findings suggest that AGT
      M235T TT genotype and T allele might be associated with decreased risk for G-AgP
      in Turkish population.

PMID- 19162261
TI  - Improved procedures for the selective chemical fragmentation of
      rhamnogalacturonans.
AB  - The structural characterization of branched rhamnogalacturonans (RGs) requires
      the availability of methods that selectively cleave the Rhap-(1-->4)-alpha-GalAp
      linkage and thereby generate oligosaccharide fragments that are suitable for mass
      spectrometric and NMR spectroscopic analyses. Enzymic cleavage of this linkage is
      often ineffective, especially in highly branched RGs. Therefore, we have
      developed an improved chemical fragmentation method based on beta-elimination of
      esterified 4-linked GalpA residues. At least 85% of the carboxyl groups of the
      GalA residues in Arabidopsis thaliana seed mucilage RG is esterified using methyl
      iodide or 3-iodopropanol in Me(2)SO containing 8% water and 1% tetrabutylammonium
      fluoride. However, beta-elimination fragmentation at pH 7.3 and 120 degrees C is
      far more extensive with hydroxypropyl-esterified RG than with methyl-esterified
      RG. The non-reducing 4-deoxy-beta-l-threo-hex-4-enepyranosyluronic acid residue
      formed by the beta-elimination reaction is completely removed by treatment with
      aqueous N-bromosuccinimide, thereby simplifying the structural characterization
      of the chemically generated oligoglycosyl fragments. This newly developed
      procedure was used to selectively fragment the branched RG from peppergrass seed
      mucilage. The products were characterized using MALDI-TOF mass spectrometry,
      glycosyl residue composition analysis, and 1 and 2D NMR spectroscopy. Our data
      show that the most abundant low-molecular weight fragments contained a backbone
      rhamnose residue substituted at O-4 with a single sidechain, and suggest that
      peppergrass seed mucilage RG is composed mainly of the repeating unit 4-O-methyl
      alpha-d-GlcpA-(1-->4)-beta-d-Galp-(1-->4)-[-->4)-alpha-d-GalpA-(1-->2)-]-alpha-l
      Rhap-(1-->.

PMID- 19162260
TI  - Understanding the relationship between PTSD and social support: the role of
      negative network orientation.
AB  - Network orientation is conceptualized as an individual's attitudes and
      expectations regarding the usefulness of support networks in coping with stress.
      The present research examined the potential for network orientation to explicate
      the well documented association between post-traumatic stress disorder (PTSD) and
      attenuated social support. Data collected from survivors of serious motor vehicle
      trauma (N=458) were used to test the hypothesis that severity of PTSD would hold
      a significant indirect relationship with social support through negative network
      orientation. Childhood victimization and elapsed time from the accident were
      examined as potential moderators of this indirect relationship. Consistent with
      hypotheses, path analyses demonstrated a significant indirect relationship
      between PTSD and social support through negative network orientation.
      Specifically, this indirect effect was the result of a direct association between
      PTSD severity and negative network orientation and an inverse association between
      negative network orientation and social support. This pattern of relationships
      was invariant across mode of PTSD assessment (interview vs. self-report). No
      moderation effects were noted. These data suggest that network orientation may be
      an important factor in understanding interface of interpersonal processes and
      post-trauma pathology.

PMID- 19162262
TI  - Optimization of 2D image reconstruction for positron emission mammography using
      IDL.
AB  - The Clear-PEM system is a prototype machine for Positron Emission Mammography
      (PEM) under development within the Portuguese PET-Mammography consortium. We have
      embedded 2D image reconstruction algorithms implemented in IDL within the
      prototype's image analysis package. The IDL implementation of these algorithms
      proved to be accurate and computationally efficient. In this paper, we present
      the implementation of the MLEM, OSEM and ART 2D iterative image reconstruction
      algorithms for PEM using IDL. C and IDL implementations are compared using
      realistic Monte Carlo simulated data. We show that IDL can be used for the easy
      implementation of image reconstruction algorithms for emission tomography.

PMID- 19162263
TI  - Month-of-birth effect on further body size in a pig model.
AB  - Previous studies unanimously confirmed the existence of a dependence of human
      body size on the month of birth. The cause of the phenomenon has not been
      identified yet, although some possible causes were proposed e.g. seasonal changes
      of climatic and nutritional conditions. This study explored the issue in an
      animal model of 20,513 pigs. We found that body weights of 6-month-old pigs were
      the highest for subjects born in February, but for 2-month-old pigs the peak fell
      in May. Any statistical correlation between the month of birth and later body
      weight may be induced by (1) a long-term effect of the month of birth on further
      growth potential (LTE), or by (2) a short-term effect of seasonal factors
      differentiating the growth rate (STE), so we developed a mathematical method to
      separate the effects. The analysis proved that (1) the observed correlations
      resulted only from the STE, with May-June being the months of the highest growth
      tempo, and that (2) there was no significant LTE. The short-term effect was
      responsible for differences between patterns of weight for 2- and 6-month-old
      animals by the month of birth: since a pig monthly gain of weight increases with
      age, it is favorable for it to be born in February to attain the greatest weight
      at the age of 6 months, whereas 2-month-old piglets are heaviest when born a
      month or two before the May/June optimum for growth. The lack of a long-term
      effect of the month of birth on pigs' weight supports the hypothesis of the
      cultural character of factor(s) responsible for the relationship between the
      month of birth and later body size in humans.

PMID- 19162264
TI  - Prevalence and correlates of influenza vaccination among non-institutionalized
      elderly people: an exploratory cross-sectional survey.
AB  - BACKGROUND: Worldwide pandemics of influenza virus caused extensive morbidity and
      mortality around the world and influenza vaccination is the most effective method
      for preventing influenza virus infection and its potentially severe
      complications. A large proportion of the Hong Kong elderly population has not
      undergone influenza vaccination. An exploration of the correlates will provide
      significant information to help identify ways of improving vaccination uptake
      among Chinese elderly people. OBJECTIVES: To explore the prevalence and
      correlates of influenza vaccination Hong Kong Chinese elderly people aged 65 or
      above. To investigate any differences in attitudes toward influenza vaccination
      among Hong Kong elderly people with different levels of cognitive and physical
      functioning. DESIGN: An exploratory cross-sectional survey with two objective
      assessments was employed. SETTINGS: Fifteen elderly centers in Hong Kong Special
      Administrative Region. PARTICIPANTS: A total of 816 Hong Kong Chinese elderly
      participants were recruited. METHODS: Face-to-face interviews were adopted to
      explore the demographic characteristics, perceptions, health status, knowledge,
      and resources of, and the influence of disease outbreaks on, influenza
      vaccination. Two objective validated instruments, the Chinese Mini-Mental State
      Examination (CMMSE) and the Barthel Index-Modified Chinese Version (MCBI) were
      used to assess the cognitive status and physical functioning of the participants.
      RESULTS: Approximately two in three individuals (62.4%) had undergone influenza
      vaccination. Lower cognitive and physical functioning scores were found among the
      non-vaccinated participants. Multivariate logistic regression analyzes revealed
      the significant correlates associated with influenza vaccination to be
      consideration of vaccination in the subsequent years (aOR=7.877; p<0.001);
      consideration of vaccination if all people aged 65 or above were eligible to
      receive free vaccination (aOR=3.024; p=0.002); the belief that there is a need to
      receive influenza vaccination following the Severe Acute Respiratory Syndrome
      (SARS) and avian influenza (aOR=2.413; p=0.001); receiving advice from nursing
      staff of elderly centers (aOR=7.161; p<0.001); the medical staff of elderly
      centers (aOR=3.771; p<0.001) or family members or friends (aOR=3.023; p=0.001).
      CONCLUSIONS: The prevalence of elderly Chinese people undergoing influenza
      vaccination remains suboptimal. The government can promote vaccination by
      educating the public about the advantages, by publicizing locations where
      vaccinations are available, and having nursing, other medical staff, family and
      friends encourage elderly people to be vaccinated. A high vaccination coverage
      rate must be ensured to achieve international goals.

PMID- 19162265
TI  - Care and caring culture as experienced by nurses working in different care
      environments: a phenomenological-hermeneutic study.
AB  - AIM: The aim is to understand and develop the concept of care and caring culture
      and to do so based on the empirical/phenomenological standpoint of nurses' lived
      experiences of working in different environments. BACKGROUND: Culture, care and
      caring are significant concepts mentioned and used in connection with nursing
      practice. In the nursing literature, the 'caring culture' as a concept is mostly
      taken for granted, and it is up to the reader to determine what caring culture
      means. METHOD: A phenomenological-hermeneutic method was used to uncover the
      meaning of lived experiences though interpretation of interviews transcribed as
      text. Seventeen nurses working on different wards were interviewed in 2006. A
      follow-up focus-group discussion was conducted with seven of the nurses 1 year
      later for validation of the findings. FINDINGS: Thematic analyses revealed five
      themes: you have to adapt to the existing care culture; seeing the invisible;
      being yourself; the strong personalities; the patients must adapt themselves to
      the circumstances. Adaptation to unwritten routines entails adaptation to the
      culture and the common value system. On wards described as "homelike", nurses may
      act in a way that reflects their own values. DISCUSSION: The care and caring
      culture can be understood from the perspective of what it means to care and from
      the perspective of how care provision is accomplished. To attain a caring culture
      founded on certain values, for example caritas, love and charity, we must first
      understand how the organization and personnel understand caring.

PMID- 19162266
TI  - Comparability of methods for LDL subfraction determination: A systematic review.
AB  - Identifying and aggressively treating individuals at elevated risk of developing
      cardiovascular disease (CVD) is critical to optimizing health outcomes. The CVD
      risk factors defined by the National Cholesterol Education Program do not fully
      predict individuals at high risk of developing CVD. Validation of potential
      methodologies against a reference method is essential to the adoption of a
      potential new risk factor to improve risk prediction. Low-density lipoprotein
      (LDL) subfraction has been advanced as a potential additional CVD risk factor.
      Currently, there is no reference method for determining LDL subfractions or
      standardizing the different methods used to measure LDL subfractions. We
      conducted a systematic review to identify reports comparing two or more methods
      of measuring LDL subfractions. Nine articles were identified that separated and
      quantified LDL subfractions by at least two methods. Comparative data were
      available for nuclear magnetic resonance vs. gel electrophoresis (GE), LipoPrint
      vs. other GE methods, ultracentrifugation vs. GE, and high performance gel
      filtration chromatography vs. GE. We found a wide range of agreement (from 7 to
      94% concordance for classifying LDL patterns) among methods for LDL subfraction
      determinations. Different criteria and definitions were used among the articles
      to classify individuals with respect to CVD risk. No study used CVD or other
      clinical outcomes as an outcome measure. In summary, the currently available
      literature does not provide adequate data about comparability in terms of test
      performance to choose one or another method to serve as a standard nor are data
      on comparability in terms of predicting CVD outcomes.

PMID- 19162267
TI  - On modelling damage process in vaginal tissue.
AB  - The goal of this study was to characterize and model the damage process in
      prolapsed vaginal tissue undergoing finite deformations. Experiments in prolapsed
      vaginal tissue revealed that a softening process occurs before tissue's rupture.
      This nonlinear damage behavior requires a continuum damage theory commonly used
      to describe the softening behavior of soft tissues under large deformations. The
      structural model here presented was built within the framework of nonlinear
      continuum mechanics. Tissue damage was simulated considering different damage
      behaviors for the matrix and the fibers. The model parameters were fit to the
      experimental data obtained from prolapsed vaginal tissue undergoing finite
      deformations in uniaxial tension tests. The tests were developed with samples cut
      along the longitudinal axis of the vagina. The damage model was able to predict
      the stress-strain behavior and the damage process accurately. The error
      estimations pointed to an excellent agreement between experimental results and
      model fittings. For all the fitted data, the normalized RMS error epsilon
      presented very low values and the coefficient of determination R2 was close to 1.

PMID- 19162268
TI  - Preparation of solid-phase microextraction fiber coated with single-walled carbon
      nanotubes by electrophoretic deposition and its application in extracting phenols
      from aqueous samples.
AB  - A novel solid-phase microextraction (SPME) Pt fiber coated with single-walled
      carbon nanotubes (SWCNTs) was prepared by electrophoretic deposition (EPD) and
      applied to the determination of phenols in aqueous samples by direct immersion
      (DI)-SPME-HPLC-UV. The results revealed that EPD was a simple and reproducible
      technique for the preparation of SPME fibers coated with SWCNTs without the use
      of adhesive. The obtained SWCNT coating did not swell in organic solvents nor
      strip off from substrate, and possessed high mechanical strength due to the
      strong Van der Waals attractions between the surfaces of the SWCNTs. The prepared
      SPME fiber was conductive since both SWCNT coating and Pt wire were conductive.
      Using Pt wire as substrate, the fiber was unbreakable. Owing to the presence of
      oxygenated groups on SWCNTs and the high surface area of SWCNTs, the SWCNT fiber
      was similar to or superior to commercial PA fiber in extracting the studied
      phenols from aqueous sample. A durability of more than 80 analyses was achieved
      for one unique fiber. Under optimized conditions, the detection limits for the
      phenols varied between 0.9 and 3.8 ng/mL, the precisions were in the range of 0.7
      3.2% (n=3), and linear ranges were within 10 and 300 ng/mL. The method was
      successfully applied to the analysis of spiked seawater and tap water samples
      with the recoveries from 87.5 to 102.0%.

PMID- 19162269
TI  - High-sensitivity microchip electrophoresis determination of inorganic anions and
      oxalate in atmospheric aerosols with adjustable selectivity and conductivity
      detection.
AB  - A sensitive and selective separation of common anionic constituents of
      atmospheric aerosols, sulfate, nitrate, chloride, and oxalate, is presented using
      microchip electrophoresis. The optimized separation is achieved in under 1 min
      and at low background electrolyte ionic strength (2.9 mM) by combining a metal
      binding electrolyte anion (17 mM picolinic acid), a sulfate-binding electrolyte
      cation (19 mM HEPBS), a zwitterionic surfactant with affinity towards weakly
      solvated anions (19 mM N-tetradecyl,N,N-dimethyl-3-ammonio-1-propansulfonate),
      and operation in counter-electroosmotic flow (EOF) mode. The separation is
      performed at pH 4.7, permitting pH manipulation of oxalate's mobility. The
      majority of low-concentration organic acids are not observed at these conditions,
      allowing for rapid subsequent injections without the presence of interfering
      peaks. Because the mobilities of sulfate, nitrate, and oxalate are independently
      controlled, other minor constituents of aerosols can be analyzed, including
      nitrite, fluoride, and formate if desired using similar separation conditions.
      Contact conductivity detection is utilized, and the limit of detection for
      oxalate (S/N=3) is 180 nM without stacking. Sensitivity can be increased with
      field-amplified sample stacking by injecting from dilute electrolyte with a
      detection limit of 19 nM achieved. The high-sensitivity, counter-EOF operation,
      and short analysis time make this separation well-suited to continuous online
      monitoring of aerosol composition.

PMID- 19162270
TI  - Liquid chromatography-tandem mass spectrometry method for the detection of marine
      lipophilic toxins under alkaline conditions.
AB  - A new LC-MS/MS method for the separation and detection of the most prominent
      marine lipophilic toxin groups comprising okadaic acid, dinophysistoxins,
      yessotoxins, azaspiracids, pectenotoxins, spirolides and some okadaic acid fatty
      acid esters has been developed. With this method 28 different marine lipophilic
      biotoxins can be analysed in a single run. Separation was achieved with an
      acetonitrile/water gradient containing ammonium hydroxide (pH 11). All toxins
      were stable under these basic conditions. Compared to chromatography using an
      acidic gradient, the limit of detection (LODs) for okadaic acid, yessotoxin,
      gymnodimine and 13-desmethyl spirolide C were improved two- to three-fold, mainly
      due to better peak shapes. The azaspiracids and pectenotoxins-2 showed comparable
      LODs under acidic and basic conditions. A major advantage of the developed method
      is that toxins can be clustered in retention time windows separated for
      positively and negatively ionized molecular ions. Therefore, there is no need for
      rapid polarity switching or two separate runs for one sample. The new method
      showed good repeatability and reproducibility and is an important step in the
      development of alternatives to the animal tests currently in use for shellfish
      toxin analysis.

PMID- 19162272
TI  - A multi-technique study of the effect of aqueous aluminium speciation on
      hydrolytic gelation of aluminium (oxy)hydroxide.
AB  - The sol-gel transformation of aqueous solutions of aluminium ions into aluminium
      (oxy)hydroxides induced by the addition of a 'soft base'-'Tris-buffer'
      (pK(a)=8.2) has been investigated using monotonous single-batch titrations and a
      combination of four complimentary techniques for monitoring pH, conductivity,
      viscosity and ultrasound parameters (velocity and attenuation). The multi-probe
      monitoring of the formation of aluminium (oxy)hydroxides enabled important stages
      of the sol-gel transformation process including: the structural conversion of
      aluminium Keggin-like polynuclear clusters into nanoparticles of aluminium
      (oxy)hydroxide; the aggregation of primary nuclei of aluminium (oxy)hydroxide
      into larger particles, and the 'arrested growth' of the aggregates with the
      formation of the three-dimensional gel network to be followed. The effect of
      aluminium ion molecular speciation on the sol-gel transformation stages is
      discussed. The data presented show that ultrasonic spectrometry, although a novel
      tool for sol-gel studies, is beneficial for the non-invasive monitoring of the
      latter stages of aluminium (oxy)hydroxide formation and its eventual breakdown in
      the presence of excess base.

PMID- 19162273
TI  - Sorption of Cm(III) and Gd(III) onto gibbsite, alpha-Al(OH)(3): A batch and TRLFS
      study.
AB  - Gd(III) and Cm(III) sorption onto a pure aluminum hydroxide, gibbsite (alpha
      Al(OH)(3)), is studied by batch experiments and time-resolved laser fluorescence
      spectroscopy (TRLFS). The experiments are conducted under argon atmosphere to
      exclude the influence of atmospheric CO(2) on solution and surface speciation.
      Batch experiments are done in two different electrolytes 0.1 M NaClO(4) and
      0.1/0.01 M NaCl at a constant gibbsite concentration of 2.2 g/L. Gadolinium
      concentrations are varied from 6.4x10(-9) to 6.4x10(-5) M. pH-dependent sorption
      is found to be congruent at Gd(III) concentrations up to 6.4x10(-7) M and a shift
      of the pH edge to higher pH values is observed for higher metal ion
      concentrations. Type of background electrolyte anion and ionic strength do not
      affect the metal ion sorption. The spectroscopic investigations are performed
      with Cm(III) and gibbsite concentrations of 2x10(-7) M and 0.5 g/L, respectively.
      From the strongly red-shifted emission spectra two different inner-sphere surface
      complexes can be identified. A third species appearing at pH 6-11 is assigned to
      a coprecipitated or incorporated Cm(III) species. This incorporated species is
      most likely formed as a consequence of the applied experimental procedure. By
      continuously increasing the pH from 4 we move from high to low gibbsite
      solubility domains. As a result, aluminum hydroxide precipitates from
      oversaturated solutions, either covering already adsorbed curium or forming a
      Al/Cm(OH)(3) coprecipitate. Fluorescence lifetimes for the surface-bound Cm(III)
      complexes and the incorporated species are at 140-150 and 180-200 micros,
      respectively. Emission bands of the Cm(III) gibbsite surface complexes appear at
      comparable wavelengths as reported for Cm(III) species bound to aluminum oxides,
      e.g., gamma-Al(2)O(3); however, lifetimes are longer. This could presumably arise
      from either shorter binding distances of the Cm to Al-O sites or a coordination
      to more surface sites.

PMID- 19162274
TI  - Structural, optical, and adsorption properties of ZnO(2)/poly(acrylic acid)
      hybrid thin porous films prepared by ionic strength controlled layer-by-layer
      method.
AB  - ZnO(2)/poly(acrylic acid) sandwich structures were prepared by layer-by-layer
      (LbL) self-assembly. The structure and optical behavior of the hybrid films were
      controlled by changing the surface charge and conformation of the poly(acrylic
      acid). The buildup of the films was followed by UV-vis absorption and reflection
      spectroscopy, atomic force microscopy (AFM), X-ray diffraction (XRD), and quartz
      crystal microbalance (QCM) measurements. It was found that the ionic strength of
      the polymer solution had a great influence on the film thickness which, in turn,
      affected the optical properties. The water vapor adsorption isotherms of the
      films determined by QCM showed an adsorption hysteresis characteristic of porous
      thin layer structures. The adsorption of water molecules inside the films changed
      the effective refractive index resulting in a change of the reflection
      properties. This phenomenon is shown to be exploited for the application of the
      films as optical sensors. The polarizability of water molecules in the adsorption
      layer was also determined. It was found that polarization of water molecules in
      the adsorption layer is much lower than in the liquid water when the surface
      coverage (Theta) is low.

PMID- 19162275
TI  - Encephalomyelitis of cattle caused by Akabane virus in southern Japan in 2006.
AB  - Six calves, aged between 55 days and 15 months, were presented between September
      and November 2006 with neurological signs including limb weakness and circling.
      Microscopical examination of the brain and spinal cord revealed the presence of
      non-suppurative encephalitis in all animals. Perivascular cuffing of lymphocytes
      and macrophages and diffuse gliosis was prominent in the cerebrum and
      degeneration and/or necrosis of neurons with vacuolation of the neuropil was
      present in the brainstem. Neuronal necrosis and neuronophagia were noted in the
      ventral horn of the spinal cord. The distribution of the lesions was closely
      related to the clinical signs displayed by each calf. Five calves presenting with
      astasia with low head carriage or torticollis had lesions throughout the central
      nervous system (CNS). The oldest calf displayed astasia caused by weakness of the
      "hindlimb" one word and had lesions largely restricted to the caudal spinal cord.
      Akabane virus (AKAV) antigens were detected immunohistochemically within neurons
      and axons in lesional tissue. Virus was not isolated from CNS tissue but the AKAV
      S gene was detected in this tissue from five calves by reverse transcriptase
      polymerase chain reaction (RT-PCR). It is suggested that AKAV infection is likely
      to have occurred during the early life period in the calves of this study.

PMID- 19162276
TI  - Cross-linguistic relations between quantifiers and numerals in language
      acquisition: evidence from Japanese.
AB  - A study of 104 Japanese-speaking 2- to 5-year-olds tested the relation between
      numeral and quantifier acquisition. A first study assessed Japanese children's
      comprehension of quantifiers, numerals, and classifiers. Relative to English
      speaking counterparts, Japanese children were delayed in numeral comprehension at
      2 years of age but showed no difference at 3 and 4 years of age. Also, Japanese 2
      year-olds had better comprehension of quantifiers, indicating that their delay
      was specific to numerals. A second study examined the speech of Japanese and
      English caregivers to explore the syntactic cues that might affect integer
      acquisition. Quantifiers and numerals occurred in similar syntactic positions and
      overlapped to a greater degree in English than in Japanese. Also, Japanese nouns
      were often dropped, and both quantifiers and numerals exhibited variable
      positions relative to the nouns they modified. We conclude that syntactic cues in
      English facilitate bootstrapping numeral meanings from quantifier meanings and
      that such cues are weaker in classifier languages such as Japanese.

PMID- 19162277
TI  - Enduring effects of severe developmental adversity, including nutritional
      deprivation, on cortisol metabolism in aging Holocaust survivors.
AB  - OBJECTIVE: In animal models, early life exposure to major environmental
      challenges such as malnutrition and stress results in persisting cardiometabolic,
      neuroendocrine and affective effects. While such effects have been associated
      with pathogenesis, the widespread occurrence of 'developmental programming'
      suggests it has adaptive function. Glucocorticoids may mediate 'programming' and
      their metabolism is known to be affected by early life events in rodents. To
      examine these relationships in humans, cortisol metabolism and cardiometabolic
      disease manifestations were examined in Holocaust survivors in relation to age at
      exposure and affective dysfunction, notably lifetime posttraumatic stress
      disorder (PTSD). METHODS: Fifty-one Holocaust survivors and 22 controls without
      Axis I disorder collected 24-h urine samples and were evaluated for psychiatric
      disorders and cardiometabolic diagnoses. Corticosteroids and their metabolites
      were assayed by gas chromatography-mass spectroscopy (GC-MS); cortisol was also
      measured by radioimmunoassay (RIA). RESULTS: Holocaust survivors showed reduced
      cortisol by RIA, and decreased levels of 5alpha-tetrahydrocortisol (5alpha-THF)
      and total glucocorticoid production by GC-MS. The latter was associated with
      lower cortisol metabolism by 5alpha-reductase and 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD) type-2. The greatest decrements were associated with
      earliest age of Holocaust exposure and less severe PTSD symptomatology.
      Cardiometabolic manifestations were associated with decreased 11beta-HSD-2
      activity. In controls, 5alpha-reductase was positively associated with trauma
      related symptoms (i.e., to traumatic exposures unrelated to the Holocaust).
      CONCLUSION: Extreme malnutrition and related stress during development is
      associated with long-lived alterations in specific pathways of glucocorticoid
      metabolism. These effects may be adaptive and link with lower risks of
      cardiometabolic and stress-related disorders in later life.

PMID- 19162278
TI  - Ischemic cerebrovascular events in patients with Chagas cardiomyopathy: a
      prospective follow-up study.
AB  - BACKGROUND: Chagas disease cardiomyopathy is a common form of dilated
      cardiomyopathy worldwide, and an important cause of stroke in Latin America. The
      long-term cumulative risk of ischemic cerebrovascular event (ICE) and its
      relation to left ventricular (LV) dysfunction have not been determined. The aims
      of this study were to describe the incidence and to evaluate the effect of LV
      ejection fraction on the risk for ICE in patients with Chagas cardiomyopathy.
      METHODS: A total of 213 consecutive patients with Chagas disease and LV systolic
      dysfunction, 131 males, mean age 48+/-12 years, were prospectively enrolled. The
      use of anticoagulation was based on clinical indications. The end point was ICE,
      which included fatal or nonfatal stroke and transient ischemic attack. Risk
      factors for events were assessed by Cox proportional-hazards analysis. RESULTS:
      Mean follow-up was 36 months; 69 patients died and seven underwent cardiac
      transplantation. The overall incidence of ICE was 2.67 events per 100
      patient/years. Independent risk factors for ICE included LV ejection fraction (HR
      0.95, 95% CI 0.91 to 0.99, p=0.009) and left atrial volume corrected for body
      surface area (HR 1.04, 95% CI 1.01 to 1.07, p=0.007), which persisted after
      adjustment for anticoagulation use. Patients with ejection fractions<or=35% had a
      relative risk of events of 3.41, as compared with the other patients. The
      presence of apical aneurysm or thrombus, age, and history of previous stroke were
      not an independent long-term risk for ICE. CONCLUSIONS: In patients with Chagas
      cardiomyopathy, the annual incidence of ICE is low. Left ventricular ejection
      fraction and indexed left atrial volume appear to be independently associated
      with these events.

PMID- 19162279
TI  - Abnormal integrity of association fiber tracts in amnestic mild cognitive
      impairment.
AB  - The association fiber tracts integrity of the inter-hemispheric and within
      hemispheric communication was poor understood in amnestic type mild cognitive
      impairment (aMCI) patients by diffusion tensor imaging (DTI). A region of
      interest-based DTI approach was applied to explore fiber tract differences
      between 22 aMCI patients and 22 well-matched normal aging. Correlations were also
      sought between fractional anisotropy (FA) values and the cognitive performance
      scores in the aMCI patients. Extensive impairment of association fiber tracts
      integrity was observed in aMCI patients, including bilateral inferior fronto
      occipital fascicles, the genu of corpus callosum, bilateral cingulate bundles and
      bilateral superior longitudinal fascicles II (SLE II) subcomponent. In addition,
      the FA value of right SLE II was significantly negatively correlated to the
      performance of Trail Making Test A and B, whilst the values of right posterior
      cingulate bundle was significantly positive correlation with MMSE score. As aMCI
      is a putative prodromal syndrome to Alzheimer's disease (AD), this study
      suggested that investigation of association fiber tracts between remote cortexes
      may yield important new data to predict whether a patient will eventually develop
      AD.

PMID- 19162281
TI  - Inhibition of hemolysate-induced iNOS and COX-2 expression by genistein through
      suppression of NF-small ka, CyrillicB activation in primary astrocytes.
AB  - Genistein is a major isoflavone compound from soybean. We investigated the anti
      inflammatory properties of genistein in primary astrocytes treated with
      hemolysate. The results indicated that genistein inhibited the expression of
      hemolysate induced iNOS and COX-2 mRNA on astrocytes. Furthermore, this compound
      inhibited the level of hemolysate-stimulated nuclear factor-kappa B (NF-small ka,
      CyrillicB). Therefore, we suggested that the effect of genistein-mediated
      inhibition of the expression hemolysate-induced iNOS and COX-2 genes is due to
      under the suppression of NF-small ka, CyrillicB activation in the transcriptional
      level.

PMID- 19162280
TI  - Deep gray matter T2 hypointensity correlates with disability in a murine model of
      MS.
AB  - Advanced MRI studies demonstrated several diffuse non-lesional features in
      multiple sclerosis, including changes detectable in gray matter areas. Standard
      T2 weighted MRI scans of deep gray matter structures, including the thalamus,
      caudate, putamen, dentate nuclei often demonstrate hypointensity. T2
      hypointensity has been shown to correlate with cognitive, neuropsychiatric and
      motor dysfunction. The exact pathogenesis of this MRI phenomenon remains unknown.
      In this manuscript, we demonstrate the first known MS animal model of deep gray
      matter T2 hypointensity. In TMEV infected SJL/J mice, gradual development of
      thalamic T2 hypointensity was noted over the disease course. Quantitative
      analysis of the hypointensity demonstrated a strong correlation between the
      degree of T2 hypointensity and rotarod detectable disability. We propose that
      this model will allow mechanistic studies investigating the pathogenesis and
      significance of deep gray matter T2 hypointensity in MS.

PMID- 19162282
TI  - Animal-sediment relationships: evaluating the 'Pearson-Rosenberg paradigm' in
      Mediterranean coastal lagoons.
AB  - We investigated the applicability of the Pearson-Rosenberg (P-R) conceptual model
      describing a generalized pattern of response of benthic communities in relation
      to organic enrichment to Mediterranean Sea coastal lagoons. Consistent with P-R
      model predictions, benthic diversity and abundance showed two different peaks at
      low (>2.5-5 mg g(-1)) and high (>25-30 mg g(-1)) total organic carbon (TOC)
      ranges, respectively. We identified TOC thresholds indicating that risks of
      reduced benthic diversity should be relatively low at TOC values<about 10 mg g(
      1), high at TOC values>about 28 mg g(-1), and intermediate at values in-between.
      Predictive ability within these ranges was high based on results of re-sampling
      simulation. While not a direct measure of causality, it is anticipated that these
      TOC thresholds should serve as a general screening-level indicator for evaluating
      the likelihood of reduced sediment quality and associated bioeffects in such
      eutrophic systems of the Mediterranean Sea.

PMID- 19162283
TI  - Chromones from the tubers of Eranthis cilicica and their antioxidant activity.
AB  - Chemical studies on the constituents of Eranthis cilicica led to isolation of ten
      chromone derivatives, two of which were previously known. Comprehensive
      spectroscopic analysis, including extensive 1D and 2D NMR data, and the results
      of enzymatic hydrolysis allowed the chemical structures of the compounds to be
      assigned as 8,11-dihydro-5-hydroxy-2,9-dihydroxymethyl-4H-pyrano[2,3
      g][1]benzoxepin-4-one, 5,7-dihydroxy-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-2
      methyl-4H-1-benzopyran-4-one, 5,7-dihydroxy-2-hydroxymethyl-8-[(2E)-4-hydroxy-3
      methylbut-2-enyl]-4H-1-benzopyran-4-one, 7-[(beta-d-glucopyranosyl)oxy]-5-hydroxy
      8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-2-methyl-4H-1-benzopyran-4-one, 7-[(beta-d
      glucopyranosyl)oxy]-5-hydroxy-2-hydroxymethyl-8-[(2E)-4-hydroxy-3-methylbut-2
      enyl]-4H-1-benzopyran-4-one, 9-[(O-beta-d-glucopyranosyl-(1-->6)-beta-d
      glucopyranosyl)oxy]methyl-8,11-dihydro-5,9-dihydroxy-2-methyl-4H-pyrano[2,3
      g][1]benzoxepin-4-one, 8,11-dihydro-5,9-dihydroxy-9-hydroxymethyl-2-methyl-4H
      pyrano[2,3-g][1]benzoxepin-4-one, and 7-[(O-beta-d-glucopyranosyl-(1-->6)-beta-d
      glucopyranosyl)oxy]methyl-4-hydroxy-5H-furo[3,2-g][1]benzopyran-5-one,
      respectively. The isolated compounds were evaluated for their antioxidant
      activity.

PMID- 19162284
TI  - Cloning and expression analysis of a wood-associated xylosidase gene (PtaBXL1) in
      poplar tension wood.
AB  - In stems of woody angiosperms responding to mechanical stress, imposed for
      instance by tilting the stem or formation of a branch, tension wood (TW) forms
      above the affected part, while anatomically distinct opposite wood (OW) forms
      below it. In poplar TW the S3 layer of the secondary walls is substituted by a
      "gelatinous layer" that is almost entirely composed of cellulose and has much
      lower hemicellulose contents than unstressed wood. However, changes in xylan
      contents (the predominant hemicelluloses), their interactions with other wall
      components and the mechanisms involved in TW formation have been little studied.
      Therefore, in the study reported here we determined the structure and
      distribution of xylans, cloned the genes encoding the xylan remodeling enzymes
      beta-xylosidases (PtaBXLi), and examined their expression patterns during tension
      wood, normal wood and opposite wood xylogenesis in poplar. We confirm that poplar
      wood xylans are substituted solely by 4-O-methylglucuronic acid in both TW and
      OW. However, although glucuronoxylans are strongly represented in both primary
      and secondary layers of OW, no 4-O-methylGlcA xylan was found in G-layers of TW.
      Four full-length BXL cDNAs encoding putative beta-xylosidases were cloned. One,
      PtaBXL1, for which xylosidase activity was confirmed by heterologous expression
      in Escherichia coli, exhibited a wood-specific expression pattern in TW. In
      conclusion, xylan as PtaBXL1, encoding beta4-xylosidase activity, are down
      regulated in TW.

PMID- 19162285
TI  - Can lifestyle factors explain why body mass index and waist-to-hip ratio increase
      with increasing tobacco consumption? The Inter99 study.
AB  - BACKGROUND: The relationship between smoking, lifestyle, and weight, body mass
      index (BMI) and waist-to-hip ratio (WH ratio) is complex, and not fully
      understood. METHODS: In total, 6784 subjects (2408 daily smokers) were included
      in a population-based study (the Inter99 study) in Denmark. Weight, height, and
      waist and hip circumference were measured. Self-reported tobacco consumption and
      lifestyle variables (dietary quality, energy intake, physical activity in leisure
      time and alcohol consumption) were registered. RESULTS: Daily smokers had a
      significantly lower BMI and significantly higher WH ratio than never smokers
      (P<0.001). Unhealthy lifestyle increased with increasing tobacco consumption
      (P<0.001 for all variables). Both BMI and WH ratio increased with increasing
      tobacco consumption. The association between increasing WH ratio and increasing
      tobacco consumption was largely explained by sociodemographic factors, rather
      than lifestyle factors. However, neither sociodemographic nor lifestyle factors
      could fully explain the increased BMI associated with heavier smoking.
      CONCLUSIONS: Sociodemographic and lifestyle factors could not fully explain why
      BMI increased with increasing daily tobacco consumption, but these factors did
      largely explain the increasing WH ratio. The relationship between BMI and tobacco
      consumption is complex, and the public needs to be informed that smoking is not a
      'diet'.

PMID- 19162286
TI  - Preliminary characterization of jejunocyte and colonocyte cell lines isolated by
      enzymatic digestion from adult and young cattle.
AB  - In the present study we developed an enzymatic approach (through the use of
      collagenase and dispase) to isolate bovine intestinal epithelial cells. Using
      this method, freshly isolated jejunocytes could be distinguished from
      simultaneously isolated colonocytes, as the jejunocytes specifically exhibited
      the small intestinal peptidase gene transcript, as well as an active alkaline
      phosphatase. The transformation of both types of cell suspension was performed by
      retroviral infection, using reproduction-defective viruses bearing the gene
      coding for the large T antigen of the leukaemia simian virus (SV40). The success
      of the transfection was demonstrated by (1) a significant increase in cell
      passage numbers (52-53 vs. 7 passages for non-transfected cells), (2) the
      detection of both the large T transcript and the large T antigen in transformed
      cells. Possible contamination and progressive substitution of bovine
      primocultures by non-bovine lineages available in the laboratory was excluded, as
      the transformed cells presented a bovine typical karyotype. Most transfected
      cells kept an epithelial morphology after transformation. They also maintained
      the expression of FABP and enterocyte specific enzymes (brush-border associated
      maltase and IAP). However, levels of specific activity of these enzymes were low,
      suggesting that cell differentiation is not completely achieved under the applied
      culture conditions.

PMID- 19162287
TI  - [Massage of the lateral pterygoid muscle in acute TMJ dysfunction syndrome].
AB  - INTRODUCTION: Massage of the lateral pterygoid muscle according to Cyriax's
      principles is an unrecognized procedure. This procedure was tried on patients
      presenting with temporomandibular joint dysfunction syndrome. MATERIAL AND
      METHODS: Fifteen patients were treated. Pain, joint clicking, measurement of
      mouth opening, lateral excursion and propulsion were recorded. Assessment was
      made before and after the massage in the same consultation. RESULTS: Joint
      clicking was solved in 80% and pain in 50% of the cases. Mouth opening increased
      by 12.8%, propulsion by 11.6% and lateral excursion by 41.3%. DISCUSSION: Massage
      of the lateral pterygoid muscle according to Cyriax's principles is a simple and
      efficient method that can be recommended for patients presenting with
      temporomandibular joint dysfunction syndrome. We performed a brief anatomical and
      radiological MRI study supporting the feasibility of lateral pterygoid muscle
      palpation.

PMID- 19162288
TI  - [Antibodies in myasthenia gravis].
AB  - In autoimmune myasthenia gravis, 75 to 80% of patients have antiacetylcholine
      receptor antibodies (anti-AChR abs) quantified by immunoprecipitation. Anti-AChR
      abs are polyclonal, directed against all AChR subunits, with a major fraction
      against the main immunogenic region, (alpha-subunit, aminoacids 67-76); they
      cause AChR loss by three mechanisms: blocking of acetylcholine binding;
      accelerated degradation or AChR due to bridging of two adjacent AChR molecules
      (antigenic modulation); lysis of postsynaptic membrane induced by complement.
      Neither anti-AChR ab level nor antigenic repertoire are correlated with disease
      severity. Studies performed on rat and human myotubes have shown that capacity of
      myasthenic patients's sera or immunoglobulins to induce AChR loss was correlated
      with anti-AChR ab titer but not with severity. Highest anti-AChR ab titers are
      found in young women with hyperplastic thymus, lowest in older patients and
      atrophic thymus. Ten to fifteen percent of babies born to myasthenic mothers
      suffer from a transitory neonatal myasthenic syndrome due to passive transfer of
      maternal anti-AChR abs. There is no correlation between clinical condition of the
      baby (presence and severity of neonatal myasthenia) and severity of maternal
      myasthenia. The risk of neonatal myasthenia is high when maternal ab titer is
      elevated (> or = 100 nM). Very rare and severe cases of foetal neonatal
      myasthenia gravis with arthrogryposis, hypomobility are due to presence in
      maternal serum of anti-AChR ab directed against foetal (gamma) AChR. In
      generalized myasthenia without anti-AChR ab, antibodies directed against MuSK, a
      postsynaptic molecule involved in AChR aggregation, are detected in around 40% of
      patients. Features of MuSK+ myasthenia are the following: strong female
      preponderance, severity (respiratory and bulbar) requiring immunosuppressants,
      facial and tongue atrophy, poor response to anticholinesterase inhibitors,
      atrophic thymus and poor response to thymectomy. Low-affinity anti-AChR abs have
      been recently reported in myasthenia gravis without anti-AChR and anti-MuSK ABS.

PMID- 19162291
TI  - Concise synthesis of stagonolide-F by ring closing metathesis approach and its
      biological evaluation.
AB  - The first total synthesis of 9-membered macrolide, stagonolide-F (3), starting
      from commercially available 1,5-pentane diol is reported. A combination of
      Jacobsen's hydrolytic kinetic resolution (HKR) and Sharpless epoxidation is used
      for the creation of two stereogenic centers, while ring-closing metathesis (RCM)
      strategy was used for the construction of the lactone ring. The molecule
      synthesized exhibited potent antifungal, antibacterial and cytotoxic activities
      against all the tested strains.

PMID- 19162290
TI  - Vaccinia virus exhibits cell-type-dependent entry characteristics.
AB  - Differing and sometimes conflicting data have been reported regarding several
      aspects of vaccinia virus (VV) entry. To address this, we used a beta
      galactosidase reporter virus to monitor virus entry into multiple cell types
      under varying conditions. Entry into HeLa, B78H1 and L cells was strongly
      inhibited by heparin whereas entry into Vero and BSC-1 cells was unaffected.
      Bafilomycin also exhibited variable and cell-type-specific effects on VV entry.
      Entry into B78H1 and BSC-1 cells was strongly inhibited by bafilomycin whereas
      entry into Vero and HeLa cells was only partially inhibited suggesting the co
      existence of both pH-dependent and pH-independent VV entry pathways in these cell
      types. Finally, entry into HeLa, B78H1, L and BSC-1 cells exhibited a lag of 6-9
      min whereas this delay was undetectable in Vero cells. Our results suggest that
      VV exploits multiple cell attachment and entry pathways allowing it to infect a
      broad range of cells.

PMID- 19162289
TI  - Vaccinia virus L1 binds to cell surfaces and blocks virus entry independently of
      glycosaminoglycans.
AB  - L1 and A28 are vaccinia virus (VACV) envelope proteins which are essential for
      cellular entry. However, their specific roles during entry are unknown. We tested
      whether one or both of these proteins might serve as receptor binding proteins
      (RBP). We found that a soluble, truncated form of L1, but not A28, bound to cell
      surfaces independently of glycosaminoglycans (GAGs). Hence, VACV A28 is not
      likely to be a RBP and functions after attachment during entry. Importantly,
      soluble L1 inhibited both binding and entry of VACV in GAG-deficient cells,
      suggesting that soluble L1 blocks entry at the binding step by competing with the
      virions for non-GAG receptors on cells. In contrast, soluble A27, a VACV protein
      which attaches to GAGs but is non-essential for virus entry, inhibited binding
      and entry of VACV in a GAG-dependent manner. To our knowledge, this is the first
      report of a VACV envelope protein that blocks virus binding and entry
      independently of GAGs.

PMID- 19162292
TI  - A new approach to quantify the degradation kinetics of linuron with UV, ozonation
      and UV/O3 processes.
AB  - The degradation of linuron, one of phenylurea herbicides, was investigated for
      its reaction kinetics by different treatment processes including ultraviolet
      irradiation (UV), ozonation (O3), and UV/O3. The decay rate of linuron by UV/O3
      process was found to be around 3.5 times and 2.5 times faster than sole-UV and
      ozone-alone, respectively. Experimental results also indicate overall rate
      constants increased exponentially with pH above 9.0 while the increase of rate
      constants with pH below 9 is insignificant in O3 system. All dominant parameters
      involved in the three processes were determined in the assistant of proposed
      linear models in this study. The approach was found useful in predicting the
      process performances through the quantification of quantum yield (Phi(LNR)) (rate
      constant for the formation of free radical HOO(.-) from ozone decomposition at
      high pH), rate constant of linuron with ozone ((k(O3,LNR)), rate constant of
      linuron with hydroxyl radical (k(OH,LNR)), and alpha (the ratio of the production
      rate of OH() and the decay rate of ozone in UV/O3 system).

PMID- 19162293
TI  - Characterization of the pattern of the nongenomic signaling pathway through which
      TCDD-induces early inflammatory responses in U937 human macrophages.
AB  - 2,3,7,8-Tetrachlorodibenzo(p)dioxin (TCDD) has been known to induce inflammatory
      signaling in a number of cell types and tissues. We found that in U937
      macrophages TCDD causes rapid activation of cytosolic phospholipase A2 (cPLA2)
      within 30min as judged by the increase in the serine 505 phosphorylated form of
      cPLA2 protein and the increased cellular release of free arachidonic acid. This
      initial action of TCDD is accompanied with the up-regulation of an important
      inflammation marker, COX-2 mRNA expression within 1h, and by 3h, several other
      markers become up-regulated. These effects appear to be dependent on the initial
      increase in the intracellular concentration of Ca(2+), and activation of cPLA2
      and COX-2. A comparative study among three different human cell lines showed that
      activation of COX-2 within 1h of action of TCDD is a common feature exhibited by
      all cell lines. On the other hand, the U937 macrophage line appears to be unique
      among them with respect to its ability to activate TNF-alpha and IL-8 mRNA
      expressions, and not requiring Src kinase in propagating the initial signaling of
      cPLA2. Based on the rapidity of activation of cPLA2 and COX-2, which occurs
      within 1h of cell exposure to TCDD, when no change in mRNA expression of CYP1A1
      has been observed, it is apparent that this unique action of TCDD is carried out
      through a distinct "nongenomic" pathway which, is clearly discernable from the
      classical, "genomic" action pathway of the AhR by not requiring the participation
      of ARNT.

PMID- 19162294
TI  - Influence of surfactants on the Cu phytoremediation potential of a salt marsh
      plant.
AB  - To assess the possible effect that surfactants commonly found in the aquatic
      environment may have on the remediation potential of the salt marsh plant
      Halimione portulacoides, a non-ionic (Triton X-100) and an anionic (sodium
      dodecyl sulfate, SDS) surfactants were used. Experiments were carried out in the
      laboratory, either in hydroponics (sediment elutriate) or in sediment soaked in
      elutriate, using sediment and water from an estuarine salt marsh (Cavado River,
      NW Portugal). Groups of H. portulacoides (grown in a greenhouse) were exposed for
      6d to media with 0.16mM added Cu(II) in the absence and in the presence of each
      one of the two selected surfactants, at concentrations lower than the respective
      micellar critical concentration. Cu was determined in solutions, sediments and in
      different plant tissues before and after experiments. Plant photosynthetic
      efficiency did not indicate deletory effects of the exposure to the added
      pollutants. The non-ionic surfactant Triton X-100 and, to a lesser extent, the
      anionic surfactant SDS too, favored Cu accumulation in the plant roots but not Cu
      translocation, indicating that surfactants may favor Cu adsorption to the roots
      (phytostabilization). On the other hand, both surfactants favored Cu solubility
      from the sediment. Therefore, the presence of surfactants, which are frequently
      found in estuarine areas, as a result of urban and industrial effluent
      discharges, may condition metal distribution in those environments.

PMID- 19162295
TI  - Removal of spilled petroleum in industrial soils by spent compost of mushroom
      Pleurotus pulmonarius.
AB  - Two batches of oil-contaminated soil collected from an industrial area and one
      pile of oil-contaminated soil in a power plant were treated by the spent compost
      of mushroom Pleurotus pulmonarius (SMC). SMC contained macronutrients for
      biostimulation, possessed 1.0-1.5 U mg(-1) laccase and 0.8-0.9 U mg(-1) manganese
      peroxidase for biodegradation and harboured (11+/-3)x10(7) cfu g(-1) bacteria and
      (56+/-9)x10(4) cfu g(-1) fungi for bioaugmentation. In off-site ex situ
      bioremediation, the industrial area soil was contaminated with organic 5.4-6.9 g
      kg(-1) total petroleum hydrocarbons (TPH), 14.5-19.0 g kg(-1) oil and grease and
      95-99 mg kg(-1) di(2-ethylhexyl) phthalate (DEHP) and inorganic 104-136 mg kg(-1)
      Cu, 430-691 mg kg(-1) Pb and 477-578 mg kg(-1) Zn. The removal by 3% SMC
      amendment applied twice accounted for 56-64%, 31-33% and 51-54% disappearance of
      the TPH, oil and grease and DEHP contaminants, respectively. For the latter soil,
      one 0.3% SMC application removed 40-45% of the initial 1.2+/-0.2 g kg(-1) TPH and
      4.0+/-0.6 g kg(-1) oil and grease in 22 d. Further using four bacteria and four
      fungi inoculated onto the sterilized soil samples, samples with greater removal
      of the pollutants bore larger microbial populations. Thus SMC simultaneously
      degrades petroleum residues and reduces toxicity in less than a month.

PMID- 19162296
TI  - Influence of balance gas mixture on decomposition of dimethyl sulfide in a wire
      cylinder pulse corona reactor.
AB  - The influence of balance gas mixture on decomposition of dimethyl sulfide was
      investigated experimentally by a wire-cylinder pulse corona reactor at room
      temperature. A new type of high voltage pulse generator with a thyratron switch
      and a Blumlein pulse-forming network was used in the experiments. The experiments
      were conducted at a fixed pulse frequency of 100pps. The DMS decomposition
      efficiency as well as energy yield was investigated using varying oxygen
      concentration (0.6-21.0%), humidity (0-1.0%) and different balance gas (air,
      N(2), Ar). Breakdown voltage of DMS in Ar is lower than that of DMS in N(2), both
      of which are proportional to the gas pressures. The conversion of DMS in Ar is
      more efficient than that in N(2) and air at a fixed peak voltage. In addition, it
      is found that 5% oxygen is the optimum concentration in decomposition of DMS, due
      to higher conversion of DMS and relatively fewer yields of by products, such as
      O(3), NO(x) and SO(2). The highest DMS removal efficiency where the energy yield
      was 1.24mgkJ(-1) was achieved with the gas stream containing 0.3% H(2)O in air.

PMID- 19162297
TI  - Trivalent chromium induces oxidative stress in goldfish brain.
AB  - Although information on the effects of Cr(6+) in biological systems is abundant,
      Cr(3+) has received less attention. Toxic effects of chromium compounds are
      partially associated with activation of redox processes. Recently we found that
      Cr(6+) induced oxidative stress in goldfish tissues and the glutathione system
      was shown to play a protective role. The present study aimed to investigate free
      radical processes in brain of goldfish exposed to CrCl(3). Trivalent chromium at
      a concentration of 50 mg L(-1) was lethal and therefore we chose to examine
      sublethal dosages of 1.0-10.0 mg L(-1) in aquarium water. The levels of lipid
      peroxides and protein carbonyls (measures of oxidative damage to lipids and
      proteins) in brain increased after 96 h exposure of goldfish to Cr(3+). However,
      exposure to 1.0-10.0 mg L(-1) Cr(3+) decreased total glutathione concentration in
      brain by approximately 50-60%. Oxidized glutathione levels also fell by
      approximately 40-60% except at the 10.0 mg L(-1) dosage where they decreased by
      85%. Therefore, 10.0 mg L(-1) Cr(3+) significantly reduced the ratio
      [GSSG]/[totalGSH] to 35% of the control value. Chromium treatment did not affect
      the activity of superoxide dismutase, but reduced the activities of catalase by
      55-62% and glutathione-S-transferase by 14-21%. The activities of glucose-6
      phosphate dehydrogenase and glutathione reductase were unchanged under any
      experimental conditions used. Therefore, it can be concluded that although Cr(3+)
      exposure induced oxidative stress in goldfish brain, it failed to enhance the
      efficiency of the antioxidant system in the organ.

PMID- 19162298
TI  - Transfer of soil contaminants to home-produced eggs and preventive measures to
      reduce contamination.
AB  - Uptake studies have shown that chickens foraging on soils contaminated with
      environmental pollutants accumulate these compounds into their eggs. Home
      produced eggs thereby show higher contamination levels than commercially produced
      eggs. It was the aim of this study to identify the major source of two
      environmental pollutants in home-produced eggs, i.e. dioxins and lead, to
      formulate preventive measures to reduce the contamination levels of such eggs,
      and to assess the feasibility of the formulated measures in terms of the
      perception and behavior of private egg producers towards such measures. The major
      source of dioxins and lead in eggs, i.e. the soil, was identified by transfer
      calculations of the pollutants from the feed and soil towards eggs. Preventive
      measures to reduce soil intake or geophagy and hence egg contamination levels,
      were formulated and their feasibility evaluated through interviews with private
      chicken owners. The results show that a paved surface inside the henhouse, an
      indoor feeding place and providing a sufficient surface area per chicken were
      considered the most appropriate in terms of feasibility and willingness to apply
      the measures by the private chicken owners. To enhance the effect of the
      measures, a combination of measures supported and promoted at policy level is
      considered as a good strategy to reduce contamination levels in home-produced
      eggs.

PMID- 19162299
TI  - Historical analysis of salmon-derived polychlorinated biphenyls (PCBs) in lake
      sediments.
AB  - Several recent studies have highlighted the importance of salmon as a means to
      deliver biomagnifying contaminants to nursery lakes. There is a lack of studies,
      however, which demonstrate empirically how this source has varied through time.
      This is of great significance because past salmon-derived contaminant loading was
      potentially greater than it is today. By analyzing radiometrically dated sediment
      cores collected from ten lakes in Alaska and British Columbia (B.C.), we relate
      historical numbers of sockeye salmon spawners to SigmaPCB concentrations and
      delta(15)N values (a paleolimnological proxy for past salmon-derived nitrogen) in
      the sediments. The results confirm that sockeye salmon have provided an important
      route for PCBs to enter the lakes in the past, a finding that is especially
      evident when the data of all lakes are pooled. Significant relationships between
      sockeye salmon numbers and delta(15)N, as well as SigmaPCB concentrations and
      delta(15)N in sediments, were also found. However, it is difficult to establish
      relationships between salmon numbers, SigmaPCBs and delta(15)N in individual
      lakes. This may be due to a number of factors which may influence contaminant
      loadings to the lakes. The factors include: a) changing salmon contaminant loads
      over time resulting from a lag in the upper ocean reservoir and/or changing
      salmon feeding locations; b) greater importance of atmospheric transport in lakes
      with relatively low salmon returns; and c) increased PCB scavenging due to higher
      algae productivity in the lakes in recent years.

PMID- 19162300
TI  - Exposure to pastures fertilised with sewage sludge disrupts bone tissue
      homeostasis in sheep.
AB  - The femurs of male and female sheep (Ovis aries), aged 18 months, bred on
      pastures fertilized twice annually with sewage sludge (2.25 tonnes dry matter/ha;
      Treated; T)) or on pastures treated with inorganic fertilizer (Control; C) were
      studied, using peripheral Quantitative Computed Tomography (pQCT) and the three
      point bending test. Males were maintained on the respective treatments from
      conception to weaning and then maintained on control pastures while the females
      were maintained on the respective treatments until slaughter. T rams exhibited
      increased total bone mineral density (BMD) at the metaphyseal part of femur
      (+10.5%, p<0.01) compared with C rams but had a reduced total cross sectional
      area (CSA, -11.5%, p<0.001), trabecular CSA (-17.1%, p<0.01) and periosteal
      circumference (-5.7%, p<0.001). In the mid-diaphyseal part, T rams had an
      increased total BMD (+13.8%, p<0.0001) and stiffness (+6.4%, p<0.01) but reduced
      total CSA (-12.1%, p<0.0001) and marrow cavity (-25.8%, p<0.0001), relative to C
      rams. In ewes although pQCT analysis of neither the metaphyseal nor the mid
      diaphyseal part of the female femur bones showed any significant differences with
      treatment, the biomechanical method revealed a reduction in load at failure (
      17.3%, p<0.01) and stiffness (-10.7%, p<0.05) amongst T ewes. It is concluded
      that exposure to pollutants present in sewage sludge can perturb bone tissue
      homeostasis in sheep, but particularly in males.

PMID- 19162301
TI  - Cadmium accumulation by muskmelon under salt stress in contaminated organic soil.
AB  - Human-induced salinization and trace element contamination are widespread and
      increasing rapidly, but their interactions and environmental consequences are
      poorly understood. Phytoaccumulation, as the crucial entry pathway for biotoxic
      Cd into the human foodstuffs, correlates positively with rhizosphere salinity.
      Hypothesising that organic matter decreases the bioavailable Cd(2+) pool and
      therefore restricts its phytoextraction, we assessed the effects of four salinity
      levels (0, 20, 40 and 60 mM NaCl) and three Cd levels (0.3, 5.5 and 10.4 mg kg(
      1)) in peat soil on mineral accumulation/distribution as well as vegetative
      growth and fruit yield parameters of muskmelon (Cucumis melo L.) in a greenhouse.
      Salt stress reduced shoot biomass and fruit production, accompanied by increased
      Na and Cl and decreased K concentration in above-ground tissues. A 25- and 50-day
      exposure to salinity increased Cd accumulation in leaves up to 87% and 46%,
      respectively. Accumulation of Cd in the fruits was up to 43 times lower than in
      leaves and remained unaltered by salinity. Soil contamination by Cd enhanced its
      accumulation in muskmelon tissues by an order of magnitude compared with non
      contaminated control. In the drainage solution, concentrations of Na and Cl
      slightly exceeded those in the irrigation solution, whereas Cd concentration in
      drainage solution was lower by 2-3 orders of magnitude than the total amount
      added. Chemical speciation and distribution modelling (NICA-Donnan) using Visual
      MINTEQ showed predominance of dissolved organic ligands in Cd chemisorption and
      complexation in all treatments; however, an increase in salt addition caused a
      decrease in organic Cd complexes from 99 to 71%, with free Cd(2+) increasing up
      to 6% and Cd-chlorocomplexes up to 23%. This work highlights the importance of
      soil organic reactive surfaces in reducing trace element bioavailability and
      phytoaccumulation. Chloride salinity increased Cd accumulation in leaves but not
      in fruit peel and pulp.

PMID- 19162302
TI  - Cold surge: a sudden and spatially varying threat to health?
AB  - While cold surge is one of the most conspicuous features of the winter monsoon in
      East Asia, its impact on human health remains underexplored. Based on the
      definition by the Central Weather Bureau in Taiwan, we identified four cold
      surges between 2000 and 2003 and collected the cardiovascular disease mortality
      data 2 weeks before and 2 weeks after these events. We attempted to answer the
      following research questions: 1) whether the cold surges impose an adverse and
      immediate effect on cardiovascular mortality; 2) whether the people living in
      temperate zones have a higher tolerance of extreme temperature drop than those in
      the subtropics. With geographic weighting techniques, we not only found that the
      cardiovascular disease mortality rates increased significantly after the cold
      surges, but also discovered a spatially varying pattern of tolerance to cold
      surges. Even within a small study area such as Taiwan, human reaction to severe
      weather drop differs across space. Needless to say, in the U.S., these findings
      should be considered in redirecting policy to address populations living in warm
      places when extreme temperature drops occur.

PMID- 19162303
TI  - Management of pregnant women with mechanical heart valve prosthesis:
      thromboprophylaxis with low molecular weight heparin.
AB  - INTRODUCTION: Pregnancy increases the risk of mechanical heart valve (MHV)
      thrombosis. Warfarin is protective, but implies risks to the fetus.
      Unfractionated heparin (UFH) is less effective but does not harm the fetus. In
      general, anticoagulation is more stable and predictable with low molecular weight
      heparin (LMWH) than with UFH. METHOD: Retrospective study of 12 pregnancies with
      MHV; 6 in aortic, 4 in mitral, and 2 in both positions, treated with therapeutic
      doses of subcutaneous LMWH twice daily throughout pregnancy. Doses were adjusted
      using anti-Xa monitoring. The frequency of thrombo-embolism with various
      anticoagulation regimes was calculated based on a literature review. RESULTS:
      Median LMWH dose was 15500 IU/24 h, range 10000-20000 IU/24 h; median dose 257
      IU/kg/24 h. Median peak LMWH in blood plasma ranged 0.54-0.92 anti-Xa U/mL.
      Thromboembolism developed in two women with aortic MHV despite LMWH levels in
      target range. One had systemic embolic episodes; in the other woman valve
      thrombosis was successfully thrombolysed. Both had initially received
      subtherapeutic doses. Thrombo-embolism was not observed in ten pregnancies
      treated as recommended. The pregnancies resulted in thirteen healthy babies;
      eight delivered by Cesarean section. Bleeding occurred in two women after
      Cesarean section due to preeclampsia. CONCLUSION: Treatment with adjusted
      therapeutic doses of LMWH was successful in 10 of 12 pregnancies, and was not
      associated with fetal complications. Thromboembolism occurred in two pregnancies,
      possibly attributed to subtherapeutic doses of LMWH during the initial 3 weeks.
      Compared to UFH prophylaxis, therapeutic doses of LMWH appears to be more
      efficacious.

PMID- 19162304
TI  - Deep venous thrombosis in duplicated superficial femoral veins.

PMID- 19162305
TI  - Circulating tissue factor procoagulant activity is elevated in stable moderate to
      severe chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) patients have
      increased risk for cardiovascular mortality and venous thromboembolism. Tissue
      factor (TF) is the physiological initiating mechanism for blood coagulation and
      is pro-inflammatory. METHODS: We have studied circulating blood-borne TF
      procoagulant activity (TF-PCA), plasma coagulation factors (F) VIIa and FVIII,
      and thrombin-antithrombin (TAT) complexes in 11 stable, moderate-severe COPD
      patients, 10 free of exacerbation for >3 weeks. RESULTS: TF-PCA was increased in
      COPD patients (52.3+/-5.6 U/ml, (SE)) compared to control subjects (20.7+/-1.5,
      n=45, p<0.0001). TAT levels were increased (COPD patients: 2.99+/-0.65 ug/l;
      control subjects: 1.31+/-0.13, n=53, p<0.0001), indicating enhanced thrombin
      generation. Plasma FVIIa (the activated form of FVII) was higher in COPD (83+/-11
      mU/ml; controls, 64+/-5 mU/ml, n=20) but did not reach statistical significance.
      Plasma FVIIc and FVIII were not increased. TF-PCA levels were inversely related
      to plasma FVIIa (r=-0.80, p=0.003) and FVIIc (r=-0.76, p=0.007). CONCLUSIONS:
      Blood-borne TF-PCA is elevated and constitutes a prothrombotic and
      proinflammatory state in stable but moderate-severe COPD, and may contribute to
      the increased risk for vascular events.

PMID- 19162306
TI  - WITHDRAWN: Counselling women about hormonal therapy.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published in a supplement entitled '3rd
      International Symposium on Women's Health Issues in Thrombosis and Haemostasis'.
      The duplicate article has therefore been withdrawn.

PMID- 19162307
TI  - Correlation between plasma activity of ADAMTS-13 and coagulopathy, and prognosis
      in disseminated intravascular coagulation.
AB  - INTRODUCTION: In disseminated intravascular coagulation (DIC), widespread
      activation of intravascular coagulation accompanied with florid endothelial
      activation results in release of unusually large von Willebrand factor (ULvWF)
      from endothelium. Circulating a disintegrin-like and metalloprotease with
      thrombospondin type 1 repeats (ADAMTS)-13 may be consumed through the ongoing
      cleavage of ULvWF, resulting in a secondary deficiency of ADAMTS-13 in DIC. We
      determined whether ADAMTS-13 activity showed a significant correlation with the
      activation status of the coagulation system and hospital mortality in DIC.
      MATERIALS AND METHODS: ADAMTS-13 activity was assayed by fluorescence resonance
      energy transfer assay in 97 patients who were clinically suspected to have DIC.
      RESULTS: ADAMTS-13 activity gradually decreased based on the DIC score and D
      dimer levels and was correlated with the antithrombin level, representing the
      consumption of ADAMTS-13 during the ongoing coagulation process. There were no
      correlation between ADAMTS-13 activity and neutrophil CD64 expression as a
      neutrophil activation marker and circulating IL-6 level as an inflammatory
      marker. Patients with a low activity of ADAMTS-13 (< or = 56.4%) had a poor
      survival rate compared to patients with a high activity of ADAMTS-13.
      CONCLUSIONS: We conclude that ADAMTS-13 activity is strongly correlated with the
      severity of coagulopathy and hospital mortality. ADAMTS-13 may serve as a
      diagnostic and prognostic marker of DIC.

PMID- 19162308
TI  - Molecular interactions in cancer cell metastasis.
AB  - Metastasis, the process by which cancer cells leave the primary tumour,
      disseminate and form secondary tumours at anatomically distant sites, is a
      serious clinical problem as it is disseminated disease, which is often impossible
      to eradicate successfully, that causes the death of most cancer patients.
      Metastasis results from a complex molecular cascade comprising many steps, all of
      which are interconnected through a series of adhesive interactions and invasive
      processes as well as responses to chemotactic stimuli. In spite of its clinical
      significance, it remains incompletely understood. This review provides an
      overview of some of the molecular interactions that are critical to metastasis.
      It summarises the principle molecular players in the major steps of the
      metastatic cascade. These are: (1) tumour angiogenesis, (2) disaggregation of
      tumour cells from the primary tumour mass, mediated by cadherins and catenins,
      (3) invasion of, and migration through, the basement membrane (BM) and
      extracellular matrix (ECM) surrounding the tumour epithelium, and subsequent
      invasion of the BM of the endothelium of local blood vessels. This is mediated
      through integrins and proteases, including urokinase form of plasminogen
      activator (uPA), matrix metalloproteinases (MMPs) and cathepsins, (4)
      intravasation of the tumour cells into the blood vessels prior to hematogeneous
      dissemination to distant sites, (5) adhesion of the circulating tumour cells to
      the endothelial cell lining at the capillary bed of the target organ site. This
      occurs through adhesive interactions between cancer cells and endothelial cells
      involving selectins, integrins and members of the immunoglobulin superfamily
      (IgSF), (6) invasion of the tumour cells through the endothelial cell layer and
      surrounding BM (extravasation) and target organ tissue and (7) the development of
      secondary tumour foci at the target organ site.

PMID- 19162310
TI  - Patterns of metastasis in sex cord-stromal tumors of the ovary: can routine
      staging lymphadenectomy be omitted?
AB  - OBJECTIVE: Given the paucity of data regarding the patterns of metastasis from
      ovarian sex cord-stromal tumors (SCSTs), we sought to determine the risk of lymph
      node metastasis in patients with SCSTs. METHODS: A retrospective chart review was
      performed after clinical and pathology databases were queried for ovarian SCST
      patients who were treated at our institution between 1985 and 2005. RESULTS: We
      identified 262 patients with pathology-confirmed ovarian SCSTs; 5 had additional
      non-stromal histology and were excluded, leaving 257 evaluable patients. Of these
      patients, 178 had adult granulosa cell tumors, 27 had juvenile granulosa cell
      tumors, 31 had Sertoli-Leydig cell tumors, 6 had sex cord tumors with annular
      tubules, 13 had mixed SCSTs, and 2 had SCSTs not otherwise specified. Our
      evaluation showed that 111 patients underwent a complete or partial staging
      procedure; 75 had stage I disease, 11 had stage II disease, and 25 had stage III
      disease. Fifty-eight of these 111 patients (52%) had lymph nodes removed as part
      of the staging procedure. Of the 58 patients who had lymph nodes sampled during
      the primary surgery, none had positive nodes. Of 117 patients whose disease
      eventually recurred, 6 patients (5.1%) had nodal metastases at the time of
      recurrence. Three of these patients had negative lymph nodes at initial staging.
      CONCLUSIONS: Lymph node metastasis in ovarian SCSTs is rare. These findings
      suggest that lymphadenectomy may be omitted when staging patients with ovarian
      SCSTs.

PMID- 19162309
TI  - Phase II trial of single agent cetuximab in patients with persistent or recurrent
      epithelial ovarian or primary peritoneal carcinoma with the potential for dose
      escalation to rash.
AB  - OBJECTIVES: Determine if cetuximab dose escalation to induce grade 2 rash
      correlates with anti-tumor activity and if sera-based markers could predict
      likelihood of response. METHODS: Patients with persistent/recurrent ovarian or
      primary peritoneal carcinoma received an initial dose of cetuximab 400 mg/m(2),
      then 250 mg/m(2) weekly for two 3-week cycles. Patients who had stable disease
      (SD) and <grade 2 rash were dose escalated in 75 mg/m(2) increments every 3 weeks
      until grade 2 rash or to a maximum weekly dose of 400 mg/m(2). Pre- and post
      treatment serum samples were evaluated for potential predictive markers of
      response. RESULTS: One of 25 patients achieved partial remission (PR) and 9
      patients had SD. The median progression free survival was 2.1 months; the 1-year
      survival rate was 54.8%. Rash (96%) was the most common drug-related adverse
      event. At first response assessment, 4 patients remained at 250 mg/m(2); 8
      patients were dose-escalated to 325 mg/m(2); of these, 4 ultimately were
      increased to 400 mg/m(2). Patients with progressive disease (PD) were removed
      from the study. Ninety-two serologic markers were analyzed from 20 patients to
      identify markers associated with clinical activity and/or predictive of outcome.
      Pretreatment levels of twelve markers were significantly elevated in patients
      exhibiting PD versus SD or PR; however, changes in marker levels during the
      course of treatment were not significant indicators of response. CONCLUSIONS:
      Single-agent cetuximab showed minimal activity in patients with recurrent ovarian
      cancer. Patients with elevated levels of 12 serologic markers at baseline were
      more likely to have earlier disease progression.

PMID- 19162311
TI  - Endometrial expression of selected transcripts involved in prostaglandin
      synthesis in cows with endometritis.
AB  - Several cytokines and prostaglandins play an important role in preparing the
      endometrium for implantation and mediating pro-inflammatory events. The aim of
      the present study was to examine mRNA expression of interleukin 1alpha (IL
      1alpha), interleukin receptor antagonist (IL-1-RN), cytosolic prostaglandin E
      synthase (cPGES), microsomal PGES (mPGES-1 and mPGES-2) and lipocalin-type PGDS
      (L-PGDS) in the bovine endometrium. Endometrial epithelium samples were collected
      ex vivo from cows with different status of health at day 21-27 postpartum on a
      dairy farm. Three groups (n=9 animals each) were defined: (1) healthy cows with
      no signs of endometritis (control group), (2) cows with subclinical endometritis,
      and (3) cows with signs of clinical endometritis. Oestrous cycle-dependent mRNA
      expression pattern was investigated using bovine endometrial epithelial cells
      from healthy uteri collected at the abattoir. These uteri were classified into
      post-ovulatory, early-to-mid luteal, late luteal or pre-ovulatory phase (n=8
      animals for each cycle phase). After collecting endometrial epithelium using the
      cytobrush-method, mRNA analysis was performed by real-time RT-PCR. L-PGDS, IL
      1alpha and IL-1-RN mRNA were expressed significantly higher (P<0.05) in the
      endometrium of cows with subclinical or clinical endometritis compared with
      healthy cows. A twofold lower cPGES mRNA expression (P<0.05) was detected in cows
      with subclinical endometritis compared to healthy cows. L-PGDS and IL-1-RN mRNA
      expression was increased (P<0.05) after ovulation compared with the pre-ovulatory
      or luteal phase, respectively. These results support the hypothesis that a dys
      regulated cytokine and/or prostaglandin profile in the uterus could be induced by
      subclinical endometritis or clinical endometritis.

PMID- 19162312
TI  - Does parenting mediate the effects of exposure to violence on violent behavior?
      An ecological-transactional model of community violence.
AB  - Three waves of longitudinal data from a high poverty sample of 1544 African
      American youth were used to test an ecological-transactional model of violence.
      SEM analyses were conducted to determine whether parenting (Time 2) mediated the
      effects of exposure to violence (Time 1) on violent behaviors (Time 3). Findings
      supported the specified model. Multigroup SEM analyses indicated that neither
      family structure nor developmental stage (early versus middle/late adolescence)
      moderated these effects. However, exposure to violence had a larger effect on
      violent behaviors in female versus male youth, although the difference was simply
      in magnitude, not direction. A final model that predicted change scores also
      provided support for the hypothesized ecological-transactional model of violence.

PMID- 19162313
TI  - Mental-health stigma: expanding the focus, joining forces.

PMID- 19162315
TI  - MRI-visible polymeric vector bearing CD3 single chain antibody for gene delivery
      to T cells for immunosuppression.
AB  - Gene therapy mediated by nonviral vectors provides great advantages over
      conventional drug therapy in inducing immunosuppression after organ
      transplantation, yet it was rarely reported because T cells are normally
      difficult to transfect. In this paper, a nonviral vector that effectively
      transports genes into T cells is developed by attaching a T cell specific ligand,
      the CD3 single chain antibody (scAb(CD3)), to the distal ends of poly(ethylene
      glycol)-grafted polyethylenimine (scAb(CD3)-PEG-g-PEI). This polymer was first
      complexed with superparamagnetic iron oxide nanoparticles (SPIONs) and was then
      used to condense plasmid DNA into nanoparticles with an ideally small size and
      low cytotoxicity. Based on a reporter gene assay, targeting ligand
      functionalization of the delivery agent leads to 16 fold of enhancement in the
      gene transfection level in HB8521 cells, a rat T lymphocyte line. This targeting
      event in cell culture was successfully imaged by MRI scan. Inspiringly, delivery
      of a therapeutic gene DGKalpha with our MRI-visible delivery agent was likewise
      efficient, resulting in a 43% inhibition in the stimulated proliferation of
      HB8521 cells as well as a 38% inhibition in the expression of a major functional
      cytokine interleukin-2 (IL-2), indicating the effective T cell anergy induced by
      gene therapy.

PMID- 19162314
TI  - Global pattern of experienced and anticipated discrimination against people with
      schizophrenia: a cross-sectional survey.
AB  - BACKGROUND: Many people with schizophrenia experience stigma caused by other
      people's knowledge, attitudes, and behaviour; this can lead to impoverishment,
      social marginalisation, and low quality of life. We aimed to describe the nature,
      direction, and severity of anticipated and experienced discrimination reported by
      people with schizophrenia. METHODS: We did a cross-sectional survey in 27
      countries, in centres affiliated to the INDIGO Research Network, by use of face
      to-face interviews with 732 participants with schizophrenia. Discrimination was
      measured with the newly validated discrimination and stigma scale (DISC), which
      produces three subscores: positive experienced discrimination; negative
      experienced discrimination; and anticipated discrimination. FINDINGS: Negative
      discrimination was experienced by 344 (47%) of 729 participants in making or
      keeping friends, by 315 (43%) of 728 from family members, by 209 (29%) of 724 in
      finding a job, 215 (29%) of 730 in keeping a job, and by 196 (27%) of 724 in
      intimate or sexual relationships. Positive experienced discrimination was rare.
      Anticipated discrimination affected 469 (64%) in applying for work, training, or
      education and 402 (55%) looking for a close relationship; 526 (72%) felt the need
      to conceal their diagnosis. Over a third of participants anticipated
      discrimination for job seeking and close personal relationships when no
      discrimination was experienced. INTERPRETATION: Rates of both anticipated and
      experienced discrimination are consistently high across countries among people
      with mental illness. Measures such as disability discrimination laws might,
      therefore, not be effective without interventions to improve self-esteem of
      people with mental illness.

PMID- 19162316
TI  - Bienzyme functionalized three-layer composite magnetic nanoparticles for
      electrochemical immunosensors.
AB  - The preparation, characterization and application of a three-layer magnetic
      nanoparticle composed of an Fe(3)O(4) magnetic core, a Prussian Blue (PB)
      interlayer and a gold shell (it can be abbreviated as Au-PB-Fe(3)O(4)) for an
      ultrasensitive and reproducible electrochemical immunosensing fabrication were
      described for the first time in this work. With the employment of the Au-PB
      Fe(3)O(4) nanoparticle, a new signal amplification strategy was developed based
      on bienzyme (horseradish peroxidase and glucose oxidase) functionalized Au-PB
      Fe(3)O(4) nanoparticles for an electrochemical immunosensing fabrication by using
      Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as model systems,
      respectively. The experiment results show that the multilabeled Au-PB-Fe(3)O(4)
      nanoparticles exhibit satisfying redox electrochemical activity and high enzyme
      catalysis activity, which predetermine their utility in high sensitivity antibody
      detection schemes. Furthermore, this immunosensor could be regenerated by simply
      using an external magnetic field which ensured a reproducible immunosensor with
      high sensitivity.

PMID- 19162318
TI  - The stimulation of healing within a rat calvarial defect by mPCL-TCP/collagen
      scaffolds loaded with rhBMP-2.
AB  - Bone morphogenetic proteins (BMPs) have been widely investigated for their
      clinical use in bone repair and it is known that a suitable carrier matrix to
      deliver them is essential for optimal bone regeneration within a specific defect
      site. Fused deposited modeling (FDM) allows for the fabrication of medical grade
      poly epsilon-caprolactone/tricalcium phosphate (mPCL-TCP) scaffolds with high
      reproducibility and tailor designed dimensions. Here we loaded FDM fabricated
      mPCL-TCP/collagen scaffolds with 5 microg recombinant human (rh)BMP-2 and
      evaluated bone healing within a rat calvarial critical-sized defect. Using a
      comprehensive approach, this study assessed the newly regenerated bone employing
      micro-computed tomography (microCT), histology/histomorphometry, and mechanical
      assessments. By 15 weeks, mPCL-TCP/collagen/rhBMP-2 defects exhibited complete
      healing of the calvarium whereas the non-BMP-2-loaded scaffolds showed
      significant less bone ingrowth, as confirmed by microCT. Histomorphometry
      revealed significantly increased bone healing amongst the rhBMP-2 groups compared
      to non-treated scaffolds at 4 and 15 weeks, although the % BV/TV did not indicate
      complete mineralisation of the entire defect site. Hence, our study confirms that
      it is important to combine microCt and histomorphometry to be able to study bone
      regeneration comprehensively in 3D. A significant up-regulation of the osteogenic
      proteins, type I collagen and osteocalcin, was evident at both time points in
      rhBMP-2 groups. Although mineral apposition rates at 15 weeks were statistically
      equivalent amongst treatment groups, micro-compression and push-out strengths
      indicated superior bone quality at 15 weeks for defects treated with mPCL
      TCP/collagen/rhBMP-2. Consistently over all modalities, the progression of
      healing was from empty defect<mPCL-TCP/collagen<mPCL-TCP/collagen/rhBMP-2,
      providing substantiating data to support the hypothesis that the release of rhBMP
      2 from FDM-created mPCL-TCP/collagen scaffolds is a clinically relevant approach
      to repair and regenerate critically-sized craniofacial bone defects.

PMID- 19162317
TI  - Homogeneous and organized differentiation within embryoid bodies induced by
      microsphere-mediated delivery of small molecules.
AB  - Cell specification and tissue formation during embryonic development are
      precisely controlled by the local concentration and temporal presentation of
      morphogenic factors. Similarly, pluripotent embryonic stem cells can be induced
      to differentiate in vitro into specific phenotypes in response to morphogen
      treatment. Embryonic stem cells (ESCs) are commonly differentiated as 3D
      spheroids referred to as embryoid bodies (EBs); however, differentiation of cells
      within EBs is typically heterogeneous and disordered. In this study, we
      demonstrate that in contrast to soluble morphogen treatment, delivery of
      morphogenic factors directly within EB microenvironments in a spatiotemporally
      controlled manner using polymer microspheres yields homogeneous, synchronous and
      organized ESC differentiation. Degradable PLGA microspheres releasing retinoic
      acid were incorporated directly within EBs and induced the formation of cystic
      spheroids uniquely resembling the phenotype and structure of early streak mouse
      embryos (E6.75), with an exterior of FOXA2+ visceral endoderm enveloping an
      epiblast-like layer of OCT4+ cells. These results demonstrate that controlled
      morphogen presentation to stem cells using degradable microspheres more
      efficiently directs cell differentiation and tissue formation than simple soluble
      delivery methods and presents a unique route to study the spatiotemporal effects
      of morphogenic factors on embryonic developmental processes in vitro.

PMID- 19162319
TI  - Inhibition of cytokine and surface antigen expression in LPS-stimulated murine
      macrophages by triethylene glycol dimethacrylate.
AB  - Dental resin monomers like triethylene glycol dimethacrylate (TEGDMA) cause a
      shift in the cellular redox balance which influences redox-sensitive signaling
      pathways. The immediate response of the innate immune system to inflammatory
      challenges is controlled by related pathways. Therefore, the influence of TEGDMA
      on the expression of the pro- and anti-inflammatory cytokines TNF-alpha, IL-6,
      and IL-10 and surface antigens (CD14, CD40, CD80, CD86, CD54, MHC class I and II)
      was analyzed in RAW264.7 macrophages. No significant change in cytokine
      production or surface antigen expression was detected after the macrophages were
      treated with increasing TEGDMA concentrations for 6, 24, and 48h. However, co
      stimulation with the bacterial endotoxin lipopolysaccharide (LPS) and TEGDMA
      resulted in a concentration-dependent inhibition of LPS-induced release of TNF
      alpha, IL-6, and IL-10 by about 90% as detected by ELISA. Flow-cytometric
      analyses indicated an LPS-stimulated expression of all surface antigens. The LPS
      induced expression of CD14 was inhibited by high TEGDMA concentrations. CD40 and
      CD80 expressions were down-regulated by TEGDMA in LPS-stimulated cells, and CD86
      as well as MHC class I expression was inhibited to a lesser extent. The LPS
      stimulated expression of CD54 (ICAM-1) was increased about twofold by increasing
      TEGDMA concentrations after a 24 and 48h exposure. Thus, the ability of
      macrophages to induce an appropriate immune response is inhibited by TEGDMA which
      reduces cytokine production and expression of surface antigens.

PMID- 19162320
TI  - Dual-drug delivery system based on hydrogel/micelle composites.
AB  - We present a dual-drug delivery system (DDDS) of hydrogel/polypeptide micelle
      composites in this work. The DDDS was constructed from aspirin (Asp) dispersed
      poly(vinyl alcohol) (PVA) or Chitosan (CS)/PVA hydrogel and doxorubicin (DOX)
      loaded poly(L-glutamic acid)-b-poly(propylene oxide)-b-poly(L-glutamic acid)
      (GPG) micelles. Independent release behaviors of the two drugs are observed. Asp
      has a short-term release while DOX has a long-term and sustained release behavior
      in all the DDDSs. The release of DOX from all the DDDSs is environmentally
      controlled due to the pH and temperature sensitivity of the GPG micelle. Asp
      shows the pH controlled release behavior in CS/PVA/micelle DDDS due to the pH
      sensitivity of CS hydrogel. The releasing profiles were analyzed using a power
      law equation proposed by Peppas. It reveals that the release of Asp is anomalous
      transport in all the hydrogel/micelle DDDSs. The release of DOX is Fickian type
      in PVA/micelle system, and changes to anomalous transport in CS/PVA/micelle
      system according to the release exponent n.

PMID- 19162321
TI  - Polymorphisms of xenobiotic metabolizing enzymes and DNA repair genes and outcome
      in childhood acute lymphoblastic leukemia.
AB  - The interindividual variation in the activity of xenobiotic metabolizing enzymes
      and DNA repair genes could modify an individual's risk of recurrent malignancy
      and response to therapy. We investigated whether ALL outcome was related to
      polymorphisms in genes CYP2D6, MPO, EPHX1, NQO1, TS, XPD and XRCC1 in 95
      consecutive ALL children by PCR or PCR-FRLP techniques. Polymorphisms in genes
      NQO1 and TS were associated with a significantly slow response to induction
      chemotherapy and NQO1 was also associated with a lower five-year event-free
      survival. This study suggests that polymorphisms of NQO1 and TS could be
      important for patient response to induction therapy and for treatment outcome.

PMID- 19162322
TI  - Derivative (7)t(7;8): The sole karyotype abnormality in acute promyelocytic
      leukemia with PML/RARA rearrangement identified by RT-PCR and sequence analysis.

PMID- 19162323
TI  - Concentrations of PCDD/Fs, PCBs and PBDEs in breast milk of women from Catalonia,
      Spain: a follow-up study.
AB  - The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers
      (PBDEs) were determined in breast milk from women living in the vicinity of a new
      hazardous waste incinerator (HWI) in Catalonia, Spain. The results were compared
      with the levels obtained in two previous surveys carried out in 1998 (baseline
      study) and 2002. The current concentrations of PCDD/Fs in breast milk ranged from
      45 to 143 pg/g fat (2.8 to 11.2 pg WHO-TEQ/g fat), while total PCBs ranged from
      114 to 617 pg/g fat (2.8 to 17.6 pg WHO-TEQ/g fat). PBDE concentrations (sum 15
      congeners) ranged from 0.57 ng/g fat to 5.9 ng/g fat, with a mean value of 2.5
      ng/g fat. A general decrease of the concentrations for PCDD/Fs and both planar
      and total PCBs was observed. Regarding to PBDE concentrations in breast milk,
      similar levels between the 2002 and the present study were noted. The levels of
      PCDD/Fs and PCBs in milk of women living in urban areas were higher than those
      corresponding to the industrial zones (38% and 40%, respectively). However, the
      current PBDE levels were slightly lower (13%) in the urban than in the industrial
      zone. For PCDD/Fs and PCBs, the current decreases are in accordance with the
      reduction in the dietary intake of these pollutants found in recent studies
      carried out in the same area of study.

PMID- 19162324
TI  - Is complement factor H a susceptibility factor for IgA nephropathy?
AB  - There is substantial evidence to suggest that complement activation plays a
      pivotal role in the pathogenesis of IgA nephropathy. Mesangial C3 deposition is
      seen in approximately 90% of patients and polymeric IgA has been shown to
      activate the alternative and lectin pathways. In addition there have been reports
      of deficiency and mutations in the serum complement regulator factor H (CFH) in
      association with IgA nephropathy. In this study we have examined the hypothesis
      that CFH is a susceptibility factor for IgA nephropathy. In 46 IgA nephropathy
      patients we undertook genotyping of three CFH SNPS (rs3753394, rs3753396 and
      rs1065489). There was no significant difference in the allele frequency of these
      3 SNPs between the patients and normal controls. In the same group of patients we
      undertook mutation screening of CFH exons 18-23 using direct sequencing and found
      no abnormalities. All the patients had a normal serum factor H concentration. In
      this small cohort of IgA nephropathy patients we have not found evidence to
      support the hypothesis that factor H is a major susceptibility factor for the
      disease.

PMID- 19162325
TI  - The vacuolar serine protease, a cross-reactive allergen from Cladosporium
      herbarum.
AB  - Subtilisin-like serine proteases make up one of the most important allergen
      families regarding the number of individual allergens. Previously, fungal
      subtilisin-like serine proteases have been identified from Aspergillus-,
      Penicillium-, and Trichophyton-species having a prevalence of IgE-reactivity
      between 33% and 80%. Since IgE-cross-reactivity is a common phenomenon within
      fungal species we wanted to know whether this protein also represents an allergen
      in Cladosporium herbarum. Hence, a screening of a C. herbarum cDNA library was
      performed using the coding sequence of the Penicillium oxalicum vacuolar serine
      protease (Pen o 18) as hybridization probe, ending up with a full-length clone.
      Biochemical and immunological characterization of this clone revealed that C.
      herbarum vacuolar serine protease most likely is synthesized as a precursor with
      an N-terminal pro-enzyme sequence and represents a minor allergen (Cla h 9) with
      a prevalence of IgE-reactivity of 15.5%. Furthermore Cla h 9 specifically reacted
      with the two monoclonal antibodies FUM20 and PCM39, as do the vacuolar serine
      proteases from Aspergillus fumigatus and Penicillium species. Investigation of
      IgE-cross-reactivity between Cla h 9 and other fungal serine proteases revealed
      that cross-reactivity is higher between vacuolar than alkaline serine proteases.
      IgE-epitope mapping of Cla h 9 was done in order to test whether four Cla h 9
      peptides having a high sequence homology to previously determined Pen ch 18-IgE
      epitopes also harbour IgE-epitopes. Three-dimensional models of the vacuolar
      serine proteases from C. herbarum and Penicillium chrysogenum were generated for
      the three-dimensional localization of the Cla h 9- and Pen ch 18- IgE-reactive
      and -non-reactive peptides. Taken together a new C. herbarum allergen has been
      identified, which may be useful in a molecule-based approach of C. herbarum
      allergy-diagnosis and -therapy. Moreover, Cla h 9 represents a further member of
      the subtilisin-like serine protease allergen-family, which stresses the
      importance of these proteins with respect to fungal IgE-cross-reactivity.

PMID- 19162326
TI  - Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan
      specificities and tumor binding properties.
AB  - Antigen presenting cells (APC) express a variety of pattern recognition
      receptors, including the C-type lectin receptors (CLR) that specifically
      recognize carbohydrate structures expressed on self-tissue and pathogens. The CLR
      play an important role in antigen uptake and presentation and have been shown to
      mediate cellular interactions. The ligand specificity of the human macrophage
      galactose-type lectin (MGL) has been characterized extensively. Here, we set out
      to determine the glycan specificity of the murine homologues, MGL1 and MGL2,
      using a glycan array. Murine MGL1 was found to be highly specific for Lewis X and
      Lewis A structures, whereas mMGL2, more similar to the human MGL, recognized N
      acetylgalactosamine (GalNAc) and galactose, including the O-linked Tn-antigen, TF
      antigen and core 2. The generation of MGL1 and MGL2-Fc proteins allowed us to
      identify ligands in lymph nodes, and MGL1-Fc additionally recognized high
      endothelial venules. Strikingly, MGL2 interacted strongly to adenocarcinoma
      cells, suggesting a potential role in tumor immunity.

PMID- 19162327
TI  - Evaluation of insulin-mimetic activities of vanadyl and zinc(II) complexes from
      the viewpoint of heterocyclic bidentate ligands.
AB  - Vanadyl sulfate (VOSO(4)) has been clinically tested in diabetic patients since
      1995. Oral administrations of VOSO(4) improved the type 2 diabetic state with
      respect to plasma glucose, HbA(1c), and fructosamine levels. The development of
      toxicity by increasing the administration of VOSO(4) should be avoided. One
      method was the utilization of vanadyl complexes with coordination compounds that
      are low-toxic and low-molecular-weight ligands to enhance the permeation of the
      metal ion to lipid bilayer membrane. Over a decade we have focused on a variety
      of heterocyclic compounds as bidentate ligands for metal ions. Vanadyl and
      zinc(II) complexes of 1-substituted 3-hydroxy-2-methyl-4(1H)-pyridinethiones,
      4,5,6-substituted 1-hydroxy-2(1H)-pyrimidinones, 4-(p-substituted)phenyl-3
      hydroxythiazole-2(3H)-thiones, 3-hydroxypyrone, 1-alkyl- or 1-phenylalkyl-3
      hydroxy-2(1H)-pyridinethiones, optically active 1-substituted 3-hydroxy-4(1H)
      pyridinethiones, and 5-dialkylsulfonamido- or 5,7-bis(dialkylsulfonamido)-8
      hydroxyquinolines were prepared, and their insulin-mimetic activities were
      evaluated in terms of IC(50) values which stand for a 50% inhibitory
      concentration of the free fatty acid release from isolated rat adipocytes. In
      this article, the relationship between the insulin-mimetic activity and the
      partition coefficient, the chirality, the substituent effect, molecular weight,
      the pK(a) value, and the coordination mode was discussed. In vivo blood glucose
      lowering effects of the vanadyl complex with 1-hydroxy-4,6-dimethyl-2(1H)
      pyrimidinone in streptozotocin (STZ)-induced diabetic rats and the zinc(II)
      complexes with 4-(p-chlorophenyl)thiazole- and 4-methylthiazole-2(3H)-thione in
      KK-A(y) mice were also discussed.

PMID- 19162328
TI  - Speciation in aqueous vanadate-ligand and peroxovanadate-ligand systems.
AB  - In the present focused review, the speciation studies of aqueous vanadate-ligand
      (L) and peroxovanadate-L systems are addressed. The paper focuses solely on the
      systems studied at our department in the context of potential insulin-enhancing
      effects, including the following ligands: imidazole, alanylhistidine,
      alanylserine, lactate, picolinate, citrate, phosphate, maltol, and uridine. We
      summarise the results of detailed and thorough potentiometric (glass electrode)
      and (51)V NMR (Bruker AMX-500MHz) spectroscopic studies, performed at 25 degrees
      C in 0.150 M Na(Cl), a medium representing human blood. The importance of
      experimental conditions is discussed and illustrated. A detailed overview of our
      methodology, based on combining potentiometric and (51)V integral and chemical
      shift data by means of the computer program LAKE, is also given. We list the
      important steps of equilibrium analysis and the kinds of information available
      from different sets of NMR spectra. The ligand picolinate is chosen to exemplify
      our working method, but conclusions are drawn from all systems, reviewing trends
      and common features. An overview of all systems is given in two tables, including
      e.g. types and number of species formed. Previously unpublished modelling results
      at physiological conditions are also shown for all peroxovanadate-ligand systems.

PMID- 19162329
TI  - Vanadium treatment of type 2 diabetes: a view to the future.
AB  - 3-Hydroxy-2-methyl-4-pyrone and 2-ethyl-3-hydroxy-4-pyrone (maltol and ethyl
      maltol, respectively) have proven especially suitable as ligands for vanadyl
      ions, in potential insulin enhancing agents for diabetes mellitus. Both
      bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog,
      bis(ethylmaltolato)oxovanadium(IV) (BEOV), have the desired intermediate
      stability for pro-drug use, and have undergone extensive pre-clinical testing for
      safety and efficacy. Pharmacokinetic evaluation indicates a pattern of
      biodistribution consistent with fairly rapid dissociation and uptake, binding to
      serum transferrin for systemic circulation and transport to tissues, with
      preferential uptake in bone. These bis-ligand oxovanadium(IV) (VOL(2)) compounds
      have a clear advantage over inorganic vanadyl sulfate in terms of bioavailability
      and pharmaceutical efficacy. BEOV has now completed Phase I and has advanced to
      Phase II clinical trials. In the Phase I trial, a range of doses from 10 mg to 90
      mg BEOV, given orally to non-diabetic volunteers, resulted in no adverse effects;
      all biochemical parameters remained within normal limits. In the Phase IIa trial,
      BEOV (AKP-020), 20 mg, daily for 28 days, per os, in seven type 2 diabetic
      subjects, was associated with reductions in fasting blood glucose and %HbA1c;
      improved responses to oral glucose tolerance testing, versus the observed
      worsening of diabetic symptoms in the two placebo controls.

PMID- 19162330
TI  - Candidemia in cancer patients: impact of early removal of non-tunneled central
      venous catheters on outcome.
AB  - OBJECTIVE: To explore the impact of retention of non-tunneled central venous
      catheters (CVCs) on survival in candidemic cancer patients, where CVCs are
      commonly used and essential. A second object was to determine whether early CVC
      removal would benefit a subset of cancer patients. METHODS: We retrospectively
      evaluated 92 cancer patients who had a single, non-tunneled CVC in place.
      Patients were grouped according to CVC retention or removal; the later group was
      subdivided into early (CVC removed <or=72h after candidemia onset) and late
      removal. A Cox regression model was used for determining risk factors of adverse
      outcome and Kaplan-Meier analyses for comparing in-hospital 3-30 day survival
      among subgroups. RESULTS: Baseline characteristics were comparable between CVC
      retention (n=20) or removal (n=72) groups. CVC retention was a significant risk
      factor of poor outcome, independent of other significant prognostic host factors
      (hazard ratio 7.15, 95% confidence interval 3.51-14.53, p<0.001). Patients of
      early CVC removal (n=40) had significant better survival than those of late
      removal (n=32) (p<0.001). CONCLUSION: The results suggest that retention of CVCs
      has a negative impact on survival in candidemic cancer patients, and that early
      CVC removal should be considered in a subset of cancer patients with candidemia.

PMID- 19162331
TI  - Social anxiety and dissociation among male patients with alcohol dependency.
AB  - The aim of this study was to investigate the relationship between social anxiety
      and dissociation among male patients with alcohol dependency. Participants were
      176 male patients consecutively admitted to an alcohol dependency treatment unit.
      The Liebowitz Social Anxiety Scale, the Dissociative Experiences Scale, the Beck
      Depression Inventory, the Spielberger State and Trait Anxiety Inventory, the
      Michigan Alcoholism Screening Test, and the Symptom Checklist-90-Revised were
      administered to all participants. The dissociative (N=58, 33.0%) group had
      significantly higher social anxiety scores than the non-dissociative
      participants. Patients with a history of suicide attempt or childhood abuse had
      elevated social anxiety scores compared to those without. In multivariate
      analysis, dissociative taxon membership predicted both of the two social anxiety
      subscale scores consisting of fear/anxiety and avoidance in a highly significant
      level while trait anxiety was a significant covariant for these subscales. Among
      dissociative symptoms, only depersonalization and amnesia/fugue were predictors
      of social anxiety. Dissociation and social anxiety are interrelated among alcohol
      dependent men. This relationship may have implications for prevention and
      treatment of alcohol dependency among men with a childhood trauma history in
      particular.

PMID- 19162332
TI  - Childhood maltreatment and adult personality disorder symptoms: influence of
      maltreatment type.
AB  - The present study examines the effects of different types of childhood
      maltreatment on personality disorder symptoms in a sample of adults with no Axis
      I psychopathology. Participants reporting a history of moderate to severe
      maltreatment on the Childhood Trauma Questionnaire (n = 70) were grouped by type
      of abuse and compared with a non-abused group (n = 35) with regard to the number
      of personality disorder symptoms endorsed. Physical/sexual abuse and emotional
      abuse/neglect each were associated with elevated symptoms of all three
      personality disorder clusters. Elevated symptoms of several specific personality
      disorders were also seen, including paranoid, borderline, avoidant, dependent,
      obsessive-compulsive, and depressive personality disorder. There were no
      significant differences between the maltreatment groups. These findings indicate
      that emotional abuse/neglect and physical/sexual abuse are risk factors for a
      broad array of personality outcomes in a non-clinical sample.

PMID- 19162333
TI  - Premorbid adjustment in schizophrenia and schizoaffective disorder.
AB  - There is evidence that premorbid adjustment can differentiate schizophrenia from
      schizoaffective disorder. We recruited 41 patients with schizophrenia and 24
      patients with schizoaffective disorder without substance abuse 6 months before
      the assessment. Diagnoses were based on the Structured Clinical Interview for DSM
      IV. Psychotic symptoms were rated with the Positive and Negative Syndrome Scale,
      the Calgary Depression Scale was used to assess depressive symptoms, and the
      Global Assessment of Functioning Scale was used to rate global psychosocial
      functioning. Premorbid adjustment was evaluated with the Premorbid Adjustment
      Scale. Patients with schizophrenia showed worse premorbid adjustment compared
      with the patients with schizoaffective disorder. The areas of "peer
      relationships" and "scholastic performance" showed deficits in schizophrenia.
      Significant associations were found between premorbid adjustment life periods and
      symptom severity in both groups. Differences found between groups may be related
      to an earlier illness onset in the schizophrenic group. Premorbid adjustment may
      be a useful clinical feature to differentiate schizoaffective disorder from
      schizophrenia.

PMID- 19162334
TI  - Comparative gene expression profile in two Atlantic salmon cell lines TO and SHK
      1.
AB  - TO and SHK-1 are two Atlantic salmon (Salmo salar) cell lines isolated from head
      kidney cells and used widely in viral diagnostic and fundamental research.
      Analysis of their resting-state expression levels for a number of immune relevant
      genes revealed significant differences in expression between the two cell types
      in the absence of stimulant. TO cells expressed Arginase 1 beta and a CD4-related
      gene at a significantly higher level than SHK-1. In contrast, SHK-1 cells
      expressed type I interferon and one of its induced genes (Mx), gammaInterferon
      induced Protein (gammaIP) and InterLeukin (IL)-10 at a significantly higher level
      than TO cells. These results suggest that these two cell lines, although
      originally isolated from the same organ have potentially very different
      functional properties. The SHK-1 cell line, or a subpopulation of SHK-1 cells,
      shares characteristics with dendritic cells whilst the TO cell line shows
      characteristics more traditionally associated with macrophages.

PMID- 19162335
TI  - The analysis of IL-1 beta and its naturally occurring inhibitors in multiple
      sclerosis: The elevation of IL-1 receptor antagonist and IL-1 receptor type II
      after steroid therapy.
AB  - The aim of our investigation was to analyze the pattern of interleukin-1 (IL-1)
      family compounds: IL-1 beta, IL-1 receptor accessory protein (Acp), IL-1 receptor
      antagonist (IL-1Ra) and IL-1 receptor type II (IL-1RII) in the serum and
      cerebrospinal fluid (CSF) from 67 multiple sclerosis (MS) patients and 31
      controls. We found significantly elevated CSF levels of IL-1 beta, IL-1Ra and Acp
      in MS patients compared to controls (p=0.001), while IL-1 beta and Acp were
      significantly elevated in MS sera (p=0.001). IL-1Ra and/or IL-1 RII increased in
      sera of all 10 investigated patients after the steroid treatment for relapse. Our
      findings suggest the important beneficial role of the induction of IL-1 RII and
      IL-1Ra in MS.

PMID- 19162336
TI  - Changes in circulating dendritic cells and B-cells in patients with multiple
      sclerosis relapse during corticosteroid therapy.
AB  - We studied dendritic, myeloid (mDCs) (BDCA1+/CD19-) and plasmacytoid cells (pDCs)
      (BDCA2+/CD123+) and B-cells (CD19+) at relapse, after short intravenous
      methyloprednisolone therapy and 30 days after treatment completion (remission
      period) and results were compared with a control group of healthy volunteers. We
      confirmed the decrease in BDCA2+/CD123+ after therapy (p=0.00006) and then an
      increase (p=0.0032) in comparison to the control group. The level of B CD19+
      cells after GC therapy increased compared to the control group (p=0.00809) and
      had stabilised 30 days after therapy. The effect of methyloprednisolone on DC
      function and B-cell levels thus changes.

PMID- 19162337
TI  - Interleukin-17 as a drug target in human disease.
AB  - Interleukin (IL)-17 (now synonymous with IL-17A) is an archetype molecule for an
      entire family of IL-17 cytokines. Currently believed to be produced mainly by a
      specific subset of CD4 cells, named Th-17 cells, IL-17 is functionally located at
      the interface of innate and acquired immunity. Specifically, it induces the
      release of chemokines and growth factors from mesenchymal cells and is now
      emerging as an important local orchestrator of neutrophil accumulation in several
      mammalian organs. Furthermore, there is growing evidence that targeting IL-17
      signaling might prove useful in a variety of diseases including asthma, Crohn's
      disease, multiple sclerosis, psoriatric disease and rheumatoid arthritis. Here,
      we summarize the key aspects of the biology of IL-17 in mammals and scrutinize
      the potential pharmacological use of targeting IL-17 in humans.

PMID- 19162338
TI  - Astrocytes and the regulation of cerebral blood flow.
AB  - Moment-to-moment changes in local neuronal activity lead to dynamic changes in
      cerebral blood flow. Emerging evidence implicates astrocytes as one of the key
      players in coordinating this neurovascular coupling. Astrocytes are poised to
      sense glutamatergic synaptic activity over a large spatial domain via activation
      of metabotropic glutamate receptors and subsequent calcium signaling and via
      energy-dependent glutamate transport. Astrocyte foot processes can signal
      vascular smooth muscle by arachidonic acid pathways involving astrocytic
      cytochrome P450 epoxygenase, astrocytic cyclooxygenase-1 and smooth muscle
      cytochrome P450 omega-hydroxylase activities, and by astrocytic and smooth muscle
      potassium channels. Non-glutamatergic transmitters released from neurons, such as
      nitric oxide, cyclooxygenase-2 metabolites and vasoactive intestinal peptide,
      might modulate neurovascular signaling at the level of the astrocyte or smooth
      muscle. Thus, astrocytes have a pivotal role in dynamic signaling within the
      neurovascular unit. Important questions remain on how this signaling is
      integrated with other pathways in health and disease.

PMID- 19162340
TI  - Tau pathophysiology in neurodegeneration: a tangled issue.
AB  - Neurodegenerative tauopathies are marked by their common pathologic feature of
      aggregates formed of hyperphosphorylated tau protein, which are associated with
      synapse and neuronal loss. Changes in tau conformation result in both loss of
      normal function and gain of fibrillogenicity that leads to aggregation. Here, we
      discuss the pathophysiology of tau and emerging evidence of how changes in this
      protein might ultimately lead to neuronal death. In particular, based on recent
      evidence, we propose that a non-apoptotic caspase-associated form of death is
      occurring in tauopathy.

PMID- 19162339
TI  - Axon guidance and synaptic maintenance: preclinical markers for neurodegenerative
      disease and therapeutics.
AB  - Axon-guidance-pathway molecules are involved in connectivity and repair
      throughout life (beyond guiding brain wiring during fetal development). One study
      found that variations (single-nucleotide polymorphisms [SNPs]) in axon-guidance
      pathway genes were predictive of three Parkinson's disease (PD) outcomes
      (susceptibility, survival free of PD and age at onset of PD) in genome-wide
      association (GWA) datasets. The axon-guidance-pathway genes DCC, EPHB1, NTNG1,
      SEMA5A and SLIT3 were represented by SNPs predicting PD outcomes. Beyond GWA
      analyses, we also present relevant neurobiological roles of these axon-guidance
      pathway molecules and consider mechanisms by which abnormal axon-guidance
      molecule signaling can cause loss of connectivity and, ultimately, PD. Novel
      drugs and treatments could emerge from this new understanding.

PMID- 19162341
TI  - Predator avoidance performance of larval fathead minnows (Pimephales promelas)
      following short-term exposure to estrogen mixtures.
AB  - Aquatic organisms exposed to endocrine disrupting compounds (EDCs) at early life
      stages may have reduced reproductive fitness via disruption of reproductive and
      non-reproductive behavioral and physiological pathways. Survival to reproductive
      age relies upon optimal non-reproductive trait expression, such as adequate
      predator avoidance responses, which may be impacted through EDC exposure. During
      a predator-prey confrontation, larval fish use an innate C-start escape behavior
      to rapidly move away from an approaching threat. We tested the hypotheses that
      (1) larval fathead minnows exposed to estrogens, a primary class of EDCs,
      singularly or in mixture, suffer a reduced ability to perform an innate C-start
      behavior when faced with a threat stimulus; (2) additive effects will cause
      greater reductions in C-start behavior; and (3) effects will differ among
      developmental stages. In this study, embryos (post-fertilization until hatching)
      were exposed for 5 days to environmentally relevant concentrations of estrone
      (E1), 17beta-estradiol (E2), and 17alpha-ethinylestradiol (EE2) singularly and in
      mixture. Exposed embryos were allowed to hatch and grow in control well water
      until 12 days old. Similarly, post-hatch fathead minnows were exposed for 12 days
      to these compounds. High-speed (1000frames/s) video recordings of escape behavior
      were collected and transferred to National Institutes of Health Image for frame
      by-frame analysis of latency period, escape velocity, and total escape response
      (combination of latency period and escape velocity). When tested 12 days post
      hatch, only E1 adversely affected C-start performance of larvae exposed as
      embryos. Conversely, larvae exposed for 12 days post-hatch did not exhibit
      altered escape responses when exposed to E1, while adverse responses were seen in
      E2 and the estrogen mixture. Ethinylestradiol exposure did not elicit changes in
      escape behaviors at either developmental stage. The direct impact of reduced C
      start performance on survival, and ultimately, reproductive fitness provides an
      avenue to assess the ecological relevance of exposure in an assay of relatively
      short duration.

PMID- 19162342
TI  - An explanatory mechanism for the different decline in limb strength in older
      women.
AB  - The aim of the study was to compare the physical activity level and intensity of
      the upper and lower limbs in Brazilian women who are usually active, functionally
      independent, and living in a medium size city. Seventy-two women were assigned
      into a younger group (YG; n=38; mean age 23.08+/-2.80 years) and older group (OG;
      60.68+/-7.16 years; n=34) groups. To discriminate the physical activity level of
      the upper and lower limbs, a daily activity record questionnaire (DARQ) was
      developed based on Bouchard's three-day physical activity record (3-day PAR).
      When compared to the YG, the OG presented: (a) higher levels of daily physical
      activity for upper limbs compared to the lower limbs and (b) higher levels of
      perceived exertion for both sets of limbs. In conclusion, these results suggest
      that women change their inter-limb pattern of daily physical activity with age;
      that is, they increase upper limb activity and decrease lower limbs activity.
      Furthermore, they decrease the exertion intensity for both sets of limbs. These
      findings may help to explain the more accentuated decline in lower limbs muscle
      strength during the aging process.

PMID- 19162343
TI  - Type D personality and cardiac mortality in patients with chronic heart failure.
AB  - BACKGROUND: Clinical predictors of cardiac mortality in chronic heart failure
      (CHF) are established, but less is known about chronic psychological predictors.
      Therefore, we examined the prognostic value of Type D personality (tendency to
      experience negative feelings and inhibit self-expression) in CHF patients.
      METHODS AND RESULTS: Consecutive systolic CHF outpatients (n=232) filled in the
      Type D Scale (DS14) at baseline. Socio-demographic and clinical data were
      obtained from the medical record/cardiologist. The primary endpoint was total
      cardiac mortality (follow-up=30.7+/-11.1 months). Late (>6 months) cardiac
      mortality was the secondary endpoint. Type D patients had a higher incidence of
      total cardiac mortality (15/48=31.3%) as compared to non Type D patients
      (32/184=17.4%), OR=2.16;95%CI:1.05-4.43, p=.04. Type D personality was a near
      significant independent predictor of total cardiac mortality (OR=1.40;95%CI:0.93
      4.29, p=.08), and a significant independent predictor of late cardiac mortality,
      adjusting for sex, age and left ventricular ejection fraction (OR=2.34;95%CI:1.05
      5.26, p=.04). CONCLUSIONS: Type D personality was a near-significant independent
      predictor of total cardiac mortality, and a significant independent predictor of
      late cardiac mortality, adjusting for socio-demographics and disease-severity.
      These findings suggest that Type D personality, a chronic psychological risk
      factor, is of importance in long-term prognosis in CHF.

PMID- 19162344
TI  - Exercise-induced ST-segment elevation during treadmill exercise testing.
AB  - The exercise electrocardiogram is a commonly used non-invasive and inexpensive
      method for detection of electrocardiogram (ECG) changes secondary to myocardial
      ischemia. It has been reported that in patients with a first myocardial
      infarction and without residual ischemia, exercise-induced ST-segment elevation
      in Q leads is related to a more damaged coronary microcirculation and to less
      viable myocardium. Exercise-induced ST-segment elevation is a rare phenomenon in
      patients without prior myocardial infarction. When occurring purely during
      exercise, coronary lesions are frequent and often severe, and on the other hand
      ST-segment elevation of the recovery phase is frequently associated with normal
      arteries or less severe lesions. We present a case of exercise-induced ST-segment
      elevation in a 51-year-old Italian man. Coronary angiography revealed a
      significant left anterior descending coronary artery stenosis, a significant
      circumflex coronary artery stenosis, a significant first obtuse marginal coronary
      artery stenosis and a significant second obtuse marginal coronary artery
      stenosis. Percutaneous transluminal coronary angioplasty with implantation of
      stents was successfully performed. Also this case is illustrative of the rare
      phenomenon of exercise-induced ST-segment elevation.

PMID- 19162345
TI  - Impact of depression on quality of life assessment in heart failure.
AB  - BACKGROUND: Depression is highly prevalent in patients with chronic heart failure
      (CHF) and may bias patients' reports of their health-related quality of life
      (HRQoL). Depressed patients may rate their limitations of HRQoL worse even when
      their condition is rather good. We aimed to examine whether co-morbid depression
      alters the relationship between disease severity and HRQoL, thus compromising the
      validity of a CHF-specific HRQoL measure. METHODS: A sample of 233 outpatients
      with CHF (mean age 64.5 years, 70% male) was evaluated. Depression was measured
      with the Patient Health Questionnaire and CHF-specific HRQoL with the Kansas City
      Cardiomyopathy Questionnaire (KCCQ). CHF severity was assessed with physician
      ratings of the New York Heart Association (NYHA) functional class. RESULTS: Both
      NYHA functional class and depression independently impacted the various subscales
      of the KCCQ. Regarding the symptom- and function-related subscales, a dose
      response relationship between disease severity and HRQoL was observed also in
      depressed patients. In contrast, in the quality of life subscale covering life
      satisfaction an interaction effect of disease severity and depression was found.
      In this subscale, a dose-response relationship between increasing disease
      severity and worsening HRQoL was no longer present among the depressed.
      CONCLUSIONS: Both disease severity and depression impacted each heart failure
      specific HRQoL dimension while the presence of depression seemed to distort the
      relationship between disease severity and HRQoL in the quality of life subscale.
      As quality of life may depend more on the presence of depression than on the
      severity of CHF, assessing depression may help interpreting HRQoL scores.

PMID- 19162346
TI  - Clinical implications of the P wave duration and dispersion: relationship between
      atrial conduction defects and abnormally prolonged and fractionated atrial
      endocardial electrograms.
AB  - Atrial conduction disease provides a suitable substrate for reentry and appears
      to be a major predisposing factor for the development of atrial fibrillation. It
      was demonstrated that when depressed conduction was observed in recordings from
      human atrial muscle, the ultra-structure was usually abnormal. Areas of poorly
      coupled fibers in diseased atrial tissue with progressive fibro-degenerative
      changes may lead to abnormal electrophysiological characteristics. Structural
      inhomogeneity or local differences in electrophysiological or ultra-structural
      properties are considered to play a major role in the initiation of reentrant
      circuits due to the increased likelihood of unidirectional block of the premature
      impulse. The P wave of the electrocardiogram may show alterations that can be
      associated with atrial arrhythmias. It was shown that there is a statistical
      association between the low resting membrane potential and a prolonged P wave
      duration. Also a prolonged inter-atrial conduction time was significantly related
      to abnormal P wave morphology. In the evaluation of patients with altered P waves
      in the electrocardiogram, it is very important to keep in mind that, patients who
      have a great susceptibility to develop AF possess abnormally prolonged and
      fractionated atrial endocardial electrograms in sinus rhythm within the right
      atrium, a significantly longer P wave duration, a significantly longer intra
      atrial and inter-atrial conduction time of sinus impulses; and a significantly
      greater sinus node dysfunction and higher incidence of induction of sustained
      atrial fibrillation. Awareness of this strong association may lead to a better
      therapeutic management in individual patients.

PMID- 19162347
TI  - Age-related differences in the pathogenesis of calcific aortic stenosis: the
      potential role of resistin.
AB  - BACKGROUND: Aortic stenosis (AS) is considered as an atherosclerotic related
      process. However, there are uncertainties whether AS in the elderly is associated
      with the same pathophysiological processes as in younger patients. We
      hypothesized that the metabolic determinants of the valvular inflammatory and
      calcifying processes occurring in elderly patients are different from those
      observed earlier in life. METHODS: Among 114 patients operated for a severe AS, a
      complete plasma lipid blood profile and plasma levels of adipokines (resistin,
      leptin) were determined. The calcium content of the aortic valve was measured and
      valvular inflammation was quantified. RESULTS: Elderly patients (>or=70 years)
      had significantly lower LDL-C (p=0.02), lower LDL-C associated with small size
      particles (LDL-C <255 A) (p=0.003), and higher HDL peak particle size than
      younger patients (p=0.03). In addition, elderly patients had increased plasma
      leptin (p=0.04) and resistin (p=0.0004) levels compared to the middle-aged group
      (<70 years). In the elderly patients, higher plasma resistin blood levels were
      associated with increased valve calcium content and inflammation. CONCLUSION: The
      lipid profile of elderly patients was found less atherogenic than that of middle
      aged patients. On the other hand, older patients with AS had higher plasma level
      of resistin which was associated with the degree of valvular calcification and
      inflammation. These results suggest that, beyond lipid model of atherosclerosis,
      age-related processes affecting resistin blood levels may also be involved in the
      late development of AS.

PMID- 19162348
TI  - Cardiac myxoma presenting with sensory neuropathy.
AB  - A 51-year-old man was admitted for burning dysesthesias over the soles.
      Neurologic examination showed a pansensory loss over both feet associated with
      weakness of toes dorsiflexion. Motor conduction study of the sural nerve showed a
      significant reduction of nerve conduction velocity (21.4 m/s) suggesting a
      demyelinating neuropathy. In the following days he was referred to the
      cardiologist because of the sudden onset of a rapid atrial tachycardia, which was
      terminated by adenosine. Echocardiography showed a left atrial mass arising from
      the atrial septum consistent with the diagnosis of cardiac myxoma. The patient
      underwent cardiac surgery to remove the tumor, which was confirmed a myxoma by
      pathology. In the days following cardiac mass removal, neurological symptoms
      progressively disappeared in the absence of anti-inflammatory and steroid therapy
      and control motor conduction study showed complete normalization of nerve
      conduction velocity (54.5 m/s). Peripheral demyelinating neuropathy represented
      the first clinical presentation of cardiac myxoma in our patient and should be
      included among the possible paraneoplastic manifestations of this cardiac tumor.

PMID- 19162349
TI  - Transthoracic echocardiography of ruptured chorda tendinea.
AB  - The discovery of a left ventricular mass obliges the clinician to perform a
      differential diagnosis including tumour or lipoma versus thrombus. The discovery
      of a left ventricular outflow tract obstruction by a mitral mass also obliges the
      clinician to perform a differential diagnosis including vegetations versus
      rupture of the chordae tendineae and its assessment also presents important
      clinical implications. Echocardiographic diagnosis of rupture of the chordae
      tendineae may be difficult to make. We present a case of ruptured chorda
      tendinea. Also this case focuses attention on differential diagnosis of a mitral
      mass.

PMID- 19162350
TI  - Correction of the hypertensive response in the treadmill testing by the work
      performance improves the prediction of hypertension by ambulatory blood pressure
      monitoring and incidence of cardiac abnormalities by echocardiography: results of
      an eight year follow-up study.
AB  - BACKGROUND: Studies of the association between hypertensive response (HR) in the
      exercise treadmill testing (ETT) and end organ damage are mostly cross-sectional
      and have not used ABPM. We investigated the association of different definitions
      of HR with incidence of hypertension by ABPM and development of cardiac
      structural abnormalities. METHODS: Normotensive individuals were submitted to ETT
      and had clinical, office BP, ABPM, and echocardiogram done in the baseline
      evaluation and after 8.1+/-1.0 years of follow-up. The variation of these
      parameters and the incidence of hypertension by tertiles of BP response corrected
      by MET and by the absolute variation of BP were tested in multivariate models.
      RESULTS: 69 of the 75 (92%) participants were examined in the follow-up. The
      higher baseline office BP and ABPM, BMI and left atrial dimension in individuals
      classified at the top tertile persisted in the follow-up. Posterior wall (8.7+/
      1.4, 9.0+/-1.2, 10.0+/-1.2 mm, P=0.005), septum thickness (9.4+/-1.7, 10.1+/-2.3,
      11.0+/-1.6 mm, P=0.030), and isovolumetric relaxation time (0.73+/-0.19, 0.76+/
      0.15, 0.85+/-0.14 s, P=0.044) became significantly higher in the follow-up visit
      in the top tertile. The incidence of hypertension by ABPM was higher in
      individuals with HR defined by the top tertile in comparison with the absolute
      response >or=210 mmHg. CONCLUSIONS: The correction of the HR in the ETT by MET
      may improve the prediction of hypertension by ABPM and of cardiac structural
      abnormalities.

PMID- 19162351
TI  - Stent thrombosis is not always stent thrombosis: de novo atherosclerosis in a
      stented coronary segment.
AB  - We discuss a case of late thrombosis, 9 years after implantation of overlapping
      bare metal stents in a circumflex artery. The patient presented with an acute ST
      segment elevation infero-lateral myocardial infarction. The coronary angiogram
      revealed a sub-occlusive thrombus within the boundaries of the stents. Aspiration
      of the material was performed and pathological analysis showed, together with
      fibrin thrombus and platelet aggregates, fragments of an atherosclerotic plaque
      (parts of necrotic core with cholesterol clefts and inflammatory cells such as
      macrophages) including iron deposition, suggestive for plaque rupture. We
      conclude that this event occurred because of de novo atherosclerotic formation of
      a vulnerable, rupture-prone plaque within the boundaries of the stents.

PMID- 19162352
TI  - Seasonal variation in acute myocardial infarction.

PMID- 19162353
TI  - Right ventricular dysfunction in pulmonary hypertension.

PMID- 19162354
TI  - Polymorphism upstream of estrogen receptor alpha reverses negative regulation of
      transcription.

PMID- 19162355
TI  - Gait analysis to classify external load conditions using linear discriminant
      analysis.
AB  - There are many instances where it is desirable to determine, at a distance,
      whether a subject is carrying a hidden load. Automated detection systems based on
      gait analysis have been proposed to detect subjects that carry hidden loads.
      However, very little baseline gait kinematic analysis has been performed to
      determine the load carriage effect while ambulating with evenly distributed
      (front to back) loads on human gait. The work in this paper establishes, via high
      resolution motion capture trials, the baseline separability of load carriage
      conditions into loaded and unloaded categories using several standard lower body
      kinematic parameters. A total of 23 participants (19 for training and 4 for
      testing) were studied. Satisfactory classification of participants into the
      correct loading condition was achieved by employing linear discriminant analysis
      (LDA). Six lower body kinematic parameters including ranges of motion and path
      lengths from the phase portraits were used to train the LDA to discriminate
      loaded and unloaded walking conditions. Baseline performance from 4 participants
      who were not included in training data sets show that the use of LDA provides a
      92.5% correct classification over two loaded and unloaded walking conditions. The
      results suggest that there are gait pattern changes due to external loads, and
      LDA could be applied successfully to classify the gait patterns with an unknown
      load condition.

PMID- 19162356
TI  - Investigation of shelf-life extension of sorghum beer (Chibuku) by removing the
      second conversion of malt.
AB  - The effect of removing the second step of malt conversion in the brewing of
      Chibuku beer was investigated with the intention of extending the shelf-life of
      the product. Chibuku was brewed in the laboratory scale fermenters using Delta
      Beverages' standard brewing procedure. A variation was made where the second malt
      conversion was not conducted on one brew. The effect of increasing pasteurisation
      time was also investigated. The extension of shelf-life was determined by
      following the physicochemical and the sensory profile of the products for a
      period of ten days under sub-tropical ambient conditions. Ethanol productions
      were similar between the control and test beers (without second conversion malt).
      A product with overall acceptability of 70% was made from the brew without the
      second malt conversion and with 15 min pasteurisation at 80 degrees C. The
      product was, however, low in bite and head retention, but had less bacterial
      load, decreased acid production, and improved keeping quality by at least two
      days. However, due to contamination of the pitching yeast with lactic acid
      bacteria (LAB), total acids rapidly increased after 168 h and caused unacceptable
      sourness. Increasing pasteurisation time to 20 min reduced bacterial load of the
      wort to figures as low as 2 x 10(3) cfu/ml. General hygiene levels of the brewery
      were acceptable and no coliforms were detected in the product or contact surfaces
      along the production line. Bacterial contamination of the product mainly comes
      from the raw materials with pasteurisation greatly reducing this load. If
      improved, the procedure has the potential of extending the shelf-life of the beer
      to beyond 168 h.

PMID- 19162357
TI  - Quorum sensing and butanediol fermentation affect colonization and spoilage of
      carrot slices by Serratia plymuthica.
AB  - In this work we investigated the role of quorum sensing and specific quorum
      sensing dependent properties in the colonization and spoilage of carrot slices by
      Serratia plymuthica RVH1, a strain isolated previously from a vegetable washing
      and cutting machine in an industrial kitchen. Disinfected carrot slices were
      inoculated by immersion in a bacterial suspension and then placed in a Petri dish
      with a shallow layer of the same bacterial suspension. Subsequently, visible
      spoilage of the air-exposed upper side of the slices and the evolution of
      bacterial numbers and pH of the surrounding suspension were recorded during 19
      days. A knockout mutant in the N-acyl-homoserine lactone (AHL) synthase splI was
      clearly compromised in its ability to colonize the surface of the carrot and
      cause browning, and the addition of synthetic AHL could restore this phenotype.
      To examine in more detail which properties contribute to this phenomenon, we
      isolated mutants deficient in the production of extracellular proteases and in
      butanediol fermentation, both of which are regulated by quorum sensing in S.
      plymuthica RVH1. The protease-deficient mutant (lipB) was not affected in the
      carrot slice spoilage assay. Since RVH1 does not produce pectinolytic enzymes,
      this suggests that hydrolytic enzymes do not play a major role in produce
      spoilage by this organism. On the other hand, a budB mutant with inactive
      butanediol fermentation pathway showed strongly enhanced growth on the carrot
      slices, in spite of a reduced survival in the surrounding medium. To explain
      these results, we hypothesize that a response is induced in the carrot slices
      that suppresses bacterial colonization and outgrowth, similar to the defense
      response induced by volatile butanediol pathway products in intact plants.

PMID- 19162358
TI  - Ethylene inhibited aflatoxin biosynthesis is due to oxidative stress alleviation
      and related to glutathione redox state changes in Aspergillus flavus.
AB  - The effect of 2-chloroethyl phosphoric acid (CEPA) on aflatoxin biosynthesis, the
      expression of aflatoxin biosynthetic genes, reactive oxygen species (ROS)
      formation, cellular redox status, and enzymes involved in glutathione consumption
      and regeneration in Aspergillus flavus was investigated. The results demonstrated
      that CEPA dose dependently inhibited aflatoxin B(1) production. The expression of
      two typical genes involved in aflatoxin biosynthesis, aflR and aflD, was reduced
      after CEPA treatment at 7 d. Meanwhile, CEPA significantly reduced ROS production
      and thiobarbituric acid reactive substances (TBARS), increased the ratio of
      reduced glutathione (GSH) and oxidized glutathione (GSSG) at 5, 6 and 7 d. The
      activities of glutathione peroxidase (GPx), glutathione reductase (GR), as well
      as glucose-6-phosphate dehydrogenase (G6PDH) were significantly inhibited after
      CEPA treatment at 5, 6 and 7 d. The present study suggested that ethylene reduced
      aflatoxin production is due to oxidative stress alleviation of fungal cells and
      is related to glutathione redox state changes.

PMID- 19162359
TI  - The fishing area as a possible indicator of the infection by anisakids in
      anchovies (Engraulis encrasicolus) from southwestern Europe.
AB  - A study was conducted on the parasitization by anisakids of European anchovies
      (Engraulis encrasicolus) from the Eastern Atlantic (Gulf of Cadiz and Strait of
      Gibraltar) and Western Mediterranean (Ligurian Sea, Gulf of Lion, Catalonia coast
      and NW Alboran Sea) throughout 1998 and 1999. The anisakids detected were
      identified as third larval stages of Anisakis larva type I and Hysterothylacium
      aduncum. Global prevalence was 9.4% for Anisakis and 24.5% for H. aduncum.
      Analysis of the origin of the anchovies revealed a higher prevalence of Anisakis
      than H. aduncum in fish from the Atlantic and vice-versa in fish from the
      Mediterranean. Analysis of various fishing areas in the Western Mediterranean
      revealed a prevalence of Anisakis in fish from the Ligurian Sea that was 5-fold
      or more than in the other three areas, with a significantly greater prevalence of
      H. aduncum in fish from the NW Mediterranean than from the Spanish Mediterranean
      coast. The prevalence of infection was found to be significantly related to
      anchovy length for both Anisakis and H. aduncum. More than 55% of Anisakis larvae
      were found in the muscle. According to these data, the risk of acquiring
      anisakiasis/anisakidosis from the consumption of raw or under-cooked anchovies
      may depend upon the area in which they were caught.

PMID- 19162360
TI  - Complete remission of diabetic nephropathy in a type 1 diabetic patient with near
      nephrotic range proteinuria and reduced renal function.
AB  - There is scant knowledge on the changes in renal histological findings in type 1
      diabetic patients those initially had nephrotic proteinuria and decreased renal
      function and later had complete remission of diabetic nephropathy by
      multifactorial treatment (MFT). A 44-year-old Japanese type 1 diabetic woman
      (duration of diabetes: 17 years) with massive proteinuria (2.9 g/day) and
      decreased renal function (creatinine clearance rate (Ccr): 86 mL/min) was
      admitted. Aggressive MFT was started with intensive insulin treatment, a low
      protein and low salt diet, angiotensin converting enzyme inhibitor and a
      diuretic. Her levels of HbA1c decreased to less than 7% within 4 months, and her
      high blood pressure gradually decreased and remained around mean 116/68 mmHg. Her
      Ccr level gradually improved and reached 108 mL/min after 78 months. Her first
      renal biopsy performed before MFT demonstrated diffuse and/or global accumulation
      of periodic acid-Schiff staining-positive mesangial matrix with increased
      mesangial matrix/glomerulus ratio and tubulo-interstitial fibrosis. Her second
      renal biopsy performed 5 years after MFT demonstrated decreased mesangial
      matrix/glomerulus ratio (42.0+/-4.0% to 29.2+/-1.9% [mean+/-S.D.], p<0.001) and
      increased her number of glomerular capillaries lumen per glomerulus (47+/-11 to
      77+/-12, p<0.006). The number of vascular endothelial growth factor (VEGF)
      expressing cells in the glomerular capillary significantly increased. Increased
      tubulo-interstitial fibrosis and the thickness of glomerular basement membrane
      (GBM) seen in the first biopsy specimen had decreased in the specimen taken at
      the second biopsy. Our case provides evidence that glomerular morphological
      improvements including decreased mesangial deposit and VEGF-related
      vasculogenesis in response to MFT goes along with functional normalization of
      diabetic nephropathy, which could not be attained in type 1 diabetic patients
      that underwent pancreas transplantation.

PMID- 19162361
TI  - Eicosapentaenoic acid ameliorates steatohepatitis and hepatocellular carcinoma in
      hepatocyte-specific Pten-deficient mice.
AB  - BACKGROUND/AIMS: Eicosapentaenoic acid (EPA) has been known as a reagent for
      improving lipid metabolism and inflammation. Hepatocyte-specific Pten-deficient
      mice exhibit hepatic lesions analogous to non-alcoholic steatohepatitis (NASH).
      Therefore, we administered EPA to Pten-deficient mice to investigate the
      mechanisms of NASH. METHODS: Pten-deficient mice were assigned to a control group
      fed with a standard chow or an EPA group fed with a 5% EPA-supplemented standard
      chow. At 40 weeks, livers from each group were processed to measure triglyceride
      content, gene expression analysis, Western blotting analysis, and histological
      examination. Level of serum reactive oxygen species (ROS) was also determined.
      Forty- and 76-week-old mice were used in tumor burden experiments. RESULTS: EPA
      ameliorated hepatic steatosis in Pten-deficient mice was based on decreased
      expression of AMPKalpha1-mediated SREBP-1c and increased PPARalpha expression.
      The EPA group exhibited less severe chronic hepatic inflammation compared to the
      control group, resulting from decreased ROS formation and a dramatically low
      ratio of arachidonic acid to EPA. Moreover, EPA inhibited development of
      hepatocellular carcinoma (HCC) in Pten-deficient mice based on an inhibition of
      MAPK activity and a low ratio of oleic to stealic acid, and a reduction in ROS
      formation. CONCLUSIONS: EPA ameliorated steatohepatitis and development of HCC in
      Pten-deficient mice.

PMID- 19162362
TI  - French pediatricians' knowledge, attitudes, beliefs towards and practices in the
      management of weight problems in children.
AB  - A representative sample of 611 French pediatricians was interviewed on their
      knowledge, attitudes, beliefs towards and practices regarding childhood obesity
      through a 39-item Likert format questionnaire. A vast majority of the respondents
      regarded obesity as an illness (86.4%), 70.2% were aware that without any
      treatment an obese child has a high risk to remain obese in adulthood, 84%
      reported that managing obesity is part of their responsibility in the routine
      practice and 89.3% affirmed to systematically inform parents of obese children on
      health risks associated with obesity. At the same time, 82.4% were convinced that
      managing obesity is bound to fail and only 46.5% that it is professionally
      gratifying. However, doctors who followed a vocational training dedicated to
      obesity felt themselves more efficient in managing childhood obesity (p<0.01),
      those who knew the national recommendations were also less likely to report that
      the management of childhood obesity leads to a failure (p<0.05). Probably one of
      the main result of our study concerns doctors' perception of the relative impact
      of the different etiologic factors of obesity. Beside sedentary life, poor eating
      behavior, lack of parental concern and heredity which are cited by more than
      three-fourth of the pediatricians, an economic situation more and more insecure
      and a food industry increasingly more powerful are reported for the first time by
      doctors themselves, respectively by 59.9% and 60.8% of them, to kill the goodwill
      of health professionals. These findings reinforce the idea that the solution to
      the obesity problem does not lie just within the doctor's office and stress the
      need for prompt regulatory actions to curb obesity.

PMID- 19162363
TI  - Public and private healthcare services utilization by non-institutional elderly
      in Hong Kong: is the inverse care law operating?
AB  - OBJECTIVES: To assess the factors associated with healthcare services utilization
      by the non-institutional elderly across five types of service utilization
      (Western medicine doctors in Government clinics, private Western medicine
      doctors, Chinese medicine practitioners, Emergency Units, and hospitalization).
      METHODS: A secondary data analysis of a territory-wide cross-sectional survey
      collected by the Government among a representative sample of 4812 elderly (aged
      60 and above) in Hong Kong. RESULTS: Our analysis, based on Anderson's behavioral
      framework, shows that need factors (relating to actual or perceived illness and
      diseases) are significantly related to the healthcare services utilization
      examined. However, enabling factors, such as monthly household income per capita,
      play a significant role in determining the utilization. Although the lower-income
      elderly consult more Government clinics and less private clinics than the more
      affluent, they have a lower total utilization of healthcare services despite
      having significantly greater healthcare needs. CONCLUSIONS: This suggests a
      mismatch of need and supply within the mixed economy of private and public
      healthcare services and suggests the existence of an 'inverse care law' in Hong
      Kong amongst elderly citizens. The findings raise concerns of inequities in Hong
      Kong's healthcare system, raising implications for future healthcare reforms.

PMID- 19162364
TI  - Comparison of outcomes and costs after hip fracture surgery in three hospitals
      that have different care systems in Japan.
AB  - Hip fracture is a medical and socioeconomic problem among the 65 years and older
      population in Japan. Length of hospital stay in Japan is much longer than other
      developed countries, and the Japanese government has tried to reduce length of
      stay in order to reduce medical expenditures. The objective of this study was to
      compare outcomes and costs of health care services for patients with hip fracture
      surgery among three hospitals with different care systems in Japan. Medical
      records of patients who were 65 years or older, who had hip fracture surgery
      within the past 2.5 years were reviewed. A questionnaire was sent to patients
      and/or their family members to ask patients' health outcomes and approximate
      costs of care after discharge. Initial hospitalization costs, costs of subsequent
      transitional care hospital, elders' care services and family's salary loss were
      estimated and compared among the three hospitals after adjusting for patients'
      characteristics and treatments. The response rate of the questionnaire was 70%
      (n=149/211). Patients' outcomes (mortality and ambulatory ability) after
      discharge were comparable. Hospitals that had shorter lengths of stay reduced
      costs to themselves, but did not reduce overall costs including care after
      discharge; however, costs were even higher because patients stayed in subsequent
      hospitals longer and/or used more elders' care services. Reducing the length of
      stay in the initial acute care hospitals could be just a method of cost-shifting
      to subsequent care services and is unlikely to bring an overall cost-savings to
      the Japanese health care system.

PMID- 19162365
TI  - A new library of HEMET model: Insulin effects on hepatic metabolism.
AB  - Prediction and simulation of cell culture behaviour, under different chemical and
      physical stimuli by a mathematical model, represent an innovative way to create a
      virtual cell laboratory, where it is possible to perform and optimize
      experimental protocol, saving time and money. In silico experiments permit to
      reproduce pathological and physiological situations and make toxicological tests.
      In this paper we introduce a new library of HEMET (HEpatocyte METabolism)
      software that allows the insulin effects on hepatic metabolism to be simulated.
      This new set of nonlinear differential equations, derived from biochemical
      reactions which involve this pancreatic hormone, allows the catabolites
      concentration in hepatic cell culture after insulin infusion to be predicted. The
      validation procedures were carried out using data obtained from specifically
      designed cell experiments and from literature. A user friendly interface allows
      to easily change model parameters, rate constants and inputs simulating a wide
      range of physiological and pathological scenarios.

PMID- 19162366
TI  - Prognostic value of KRAS mutations and Ki-67 expression in stage I lung
      adenocarcinomas.
AB  - The purpose of the present study was to establish accurate prognostic markers to
      predict the post-operative recurrence of stage I lung adenocarcinomas (ADC). One
      hundred and ninety cases of stage I ADC were examined for KRAS mutations and Ki
      67 expression, and their associations with disease recurrence were analyzed. KRAS
      mutated cases showed a significantly higher risk of recurrence than cases without
      mutations (5-year disease-free survival (DFS) 61.0% vs. 85.8%, P=0.017: adjusted
      Hazard ratio (HR) 4.55, 95% Confidence Interval (CI) 1.61-12.82, P=0.004). Ki-67
      high-expressers (labeling index >10%) also showed a higher risk of recurrence
      than low-expressers (5-year DFS 68.7% vs. 93.2%, P<0.001: adjusted HR 3.84, 95%
      CI 1.18-12.45, P=0.025). Ki-67 high-expressers with KRAS mutations showed an
      additional higher risk of recurrence compared to low-expressers without mutations
      (5-year DFS 37.5% vs. 93.3%, P<0.001: adjusted HR 16.82, 95% CI 3.77-74.98,
      P<0.001) and their 5-year DFS was nearly equivalent to that of stage II non-small
      cell lung cancer (NSCLC) in our facility (37.5% vs. 37.2% for stage II NSCLC,
      p=0.577). The combined use of KRAS status and Ki-67 expression level could be an
      excellent prognostic marker to predict the post-operative recurrence of stage I
      ADC.

PMID- 19162367
TI  - Abnormal expression of p120-catenin, E-cadherin, and small GTPases is
      significantly associated with malignant phenotype of human lung cancer.
AB  - Studies on a variety of cell lines have shown that p120-catenin can directly
      regulate the stability of E-cadherin complexes and control the activity of small
      GTPases to influence cell adhesion. Despite this data, clinical studies of human
      solid tumors have not been reported to investigate these protein interactions. To
      explore the correlation between p120-catenin, E-cadherin, and small GTPases in
      human lung cancer, we examined the expression patterns of p120-catenin, E
      cadherin, RhoA, Cdc42, and Rac1, and their prognostic significance in 138
      patients with non-small cell lung cancer (NSCLC). While normal bronchial
      epithelium showed strong membrane expression of p120-catenin and E-cadherin, lung
      cancer tissues had reduced membrane expression and ectopic cytoplasmic expression
      of p120-catenin and E-cadherin. Expression of RhoA, Cdc42, and Rac1 was also
      found to be higher in tumor tissue than in normal lung tissue. A correlation
      between abnormal p120-catenin, E-cadherin expression, and overexpression of
      specific small GTPases was also associated with poor differentiation, high TNM
      stage, and lymph node metastasis in NSCLC patients. We also used an in vitro
      model to evaluate their expression, and to determine whether protein expression
      correlated with the invasive capacity of lung cancer cell lines. Consistent with
      our in vivo data, abnormal expression of p120-catenin and E-cadherin with
      overexpression of specific small GTPases were significantly associated with the
      high metastatic capacity of BE1 cells. Based on our results, we conclude that
      abnormal p120-catenin expression correlates with abnormal E-cadherin expression
      and specific small GTPase overexpression, which contribute to the malignancy
      related to NSCLC.

PMID- 19162368
TI  - Influence of the mannose receptor in host immune responses.
AB  - Mannose receptor (MR) is a C-type lectin primarily expressed by macrophages and
      dendritic cells. Its three distinct extracellular binding sites recognise a wide
      range of both endogenous and exogenous ligands, therefore MR has been implicated
      in both homeostatic processes and pathogen recognition. However, the function of
      MR in host defence is not yet clearly understood as MR-deficient animals do not
      display enhanced susceptibility to pathogens bearing MR ligands. This scenario is
      even more complex when considering the role of MR in innate immune activation as,
      even though no intracellular signalling motif has been identified at its
      cytoplasmic tail, MR has been shown to be essential for cytokine production, both
      pro-inflammatory and anti-inflammatory. Furthermore, MR might interact with other
      canonical pattern recognition receptors in order to mediate intracellular
      signalling. In this review, we have summarised recent observations relating to MR
      function in immune responses and focused on its participation in phagocytosis,
      antigen processing and presentation, cell migration and intracellular signalling.

PMID- 19162369
TI  - Differential response of antioxidant systems in leaves and roots of barley
      subjected to anoxia and post-anoxia.
AB  - Mitochondria and chloroplasts are the primary sources of reactive oxygen species
      in photosynthetic tissues. Mitochondria play a dual role in oxidative stress,
      being both ROS producers and integrators of the cell antioxidant defense systems.
      Anoxia followed by re-exposure to air may create conditions of elevated ROS
      generation in plants. The reactions of barley leaves and root antioxidant systems
      after anoxia were investigated. Alternative oxidase and low-mass antioxidants
      showed different patterns of change in leaves and roots in response to changing
      oxygen availability. Mitochondria from leaves showed a reduced AOX capacity and
      AOX protein level during post-anoxia, while the AOX capacity in root mitochondria
      increased. In leaf tissue, ascorbate and glutathione were immediately oxidized
      after restoration of aerobiosis due to the enhanced ROS production, whereas in
      roots ascorbate and glutathione became even more reduced. The capacity of
      antioxidant systems was not exceeded in either leaf or root tissue after anoxia;
      no signs of oxidative damage were observed and the respiratory activity of
      mitochondria was retained. We suggest that the leaf and root cell antioxidant
      systems react differentially to changes in oxygen concentration. In leaves, low
      mass antioxidants play the major role in ROS detoxification, while in roots,
      increased AOX capacity supports the antioxidant systems, possibly by preventing
      ROS formation.

PMID- 19162370
TI  - Performance of hand hygiene in 214 healthcare facilities in South-Western France.

PMID- 19162371
TI  - Brushes and picks used on nails during the surgical scrub to reduce bacteria: a
      randomised trial.
AB  - Though brushes are no longer used on the hands and forearms during the surgical
      scrub, they are still widely used on the nails. The aim of this study was to
      determine whether nail picks and nail brushes are effective in providing
      additional decontamination during a surgical hand scrub. A total of 164 operating
      department staff were randomised to undertake one of the following three surgical
      hand-scrub protocols: chlorhexidine only; chlorhexidine and a nail pick; or
      chlorhexidine and a nail brush. Bacterial hand sampling was conducted before and
      1h after scrubbing using a modified version of the glove juice method. No
      statistically significant differences in bacterial numbers were found between any
      two of the three intervention groups. Nail brushes and nail picks used during
      surgical hand scrubs do not decrease bacterial numbers and are unnecessary.

PMID- 19162372
TI  - Aerial dispersal of meticillin-resistant Staphylococcus aureus in hospital rooms
      by infected or colonised patients.
AB  - The aim of this study was to assess to what extent patients with meticillin
      resistant Staphylococcus aureus (MRSA) at respiratory sites shed viable MRSA into
      the air of hospital rooms. We also evaluated whether the distance from the
      patient could influence the level of contamination. Air sampling was performed
      directly onto MRSA-selective agar in 24 hospital rooms containing patients with
      MRSA colonization or infection of the respiratory tract. Samplings were performed
      in duplicate at 0.5, 1 and 2-3 m from the patients' heads. Clinical and
      environmental isolates were compared using antimicrobial resistance patterns and
      pulsed-field gel electrophoresis. MRSA strains were isolated from 21 out of 24
      rooms, in quantities varying from between 1 and 78 cfu/m3. In each of the 21
      rooms, at least one of the environmental isolates was identical to a clinical
      isolate from the patient in that room. There was no significant difference in
      MRSA counts between the distance from the patient's head and the sampler. This
      study demonstrates that most patients with MRSA infection or colonisation of the
      respiratory tract shed viable MRSA into the air of their room. The results
      emphasise the need to study MRSA in air in more detail in order to improve
      infection control recommendations.

PMID- 19162373
TI  - Mathematical model for the control of nosocomial norovirus.
AB  - A gastroenteritis outbreak in a long-term care facility was analysed by means of
      a SEIR (Susceptible, Exposed/Latent phase, Infected/Infectious, and Recovered)
      compartment model of infection dynamics in a closed population [96 beds; attack
      rate=41%; R0 (basic reproductive number)=3.74; generation time approximately 1
      day; duration of disease approximately 2 days; theoretical infinite (1000 days)
      duration of hospital stay]. The patient-turnover variation was simulated to
      determine the effect of the length of hospital stay on the endemic level of
      gastroenteritis perpetuating the epidemic phase in an open population. With all
      the other parameters held constant, the prevalence of infected patients in the
      endemic phase (50 days after the beginning of the outbreak) increased markedly
      from five to 18 cases as the hospital stay increased from one-tenth of a day (one
      day care) to one or two days; the prevalence decreased exponentially with the
      length of hospital stay, being fewer than five cases for hospital stays >50 days.
      In conclusion, the endemic prevalence of norovirus gastroenteritis is critically
      dependent on the patient turnover within hospital wards. For the usual range of
      hospital stay (0.1-20 days), the prevalence level is sufficiently elevated to
      maintain the perpetuation of gastroenteritis within the population of
      institutionalised patients. In long-term care facilities (hospital stay >20
      days), the patient turnover is sufficiently low for one to expect a spontaneous
      extinction of epidemic outbreak without endemic perpetuation. When an epidemic
      outbreak occurs in an acute-care setting, reinforcement of infection control
      measures, including closure of the ward, is required to break the transmission
      chain.

PMID- 19162374
TI  - Waterlow score to predict patients at risk of developing Clostridium difficile
      associated disease.
AB  - This study describes the development and testing of an assessment tool to predict
      the risk of patients developing Clostridium difficile-associated disease (CDAD).
      The three phases of the study include the development of the tool, prospective
      testing of the validity of the tool using 1468 patients in a medical assessment
      unit and external retrospective testing using data from 29 425 patients. In the
      first phase of the study, receiver operating characteristic (ROC) analysis
      identified the Waterlow assessment score as having the ability to predict CDAD
      (area under the curve: 0.827). The Waterlow tool was then tested prospectively
      with 1468 patients admitted to a medical assessment unit. A total of 1385
      patients (94%) had a Waterlow score <20 and 83 patients (6%) had a Waterlow score
      of > or = 20. After a three-month follow-up, six patients in the low Waterlow
      score group developed CDAD (0.4%) and 14 patients in the high score group
      developed CDAD (17%). The sensitivity and specificity of the Waterlow score to
      predict the risk of developing CDAD were 70% and 95%, respectively. Similar
      results were obtained when the tool was tested retrospectively on a large
      external patient data set. The Waterlow score appears to predict patients' risk
      of developing CDAD and although it did not identify all cases, it highlighted a
      small group of patients who had a disproportionately large number of CDAD cases.
      The Waterlow score can be used to target patients most at risk of developing
      CDAD.

PMID- 19162375
TI  - Management of infection control in dental practice.
AB  - This was an observational study in which the management policies and procedures
      associated with infection control and instrument decontamination were examined in
      179 dental surgeries by a team of trained surveyors. Information relating to the
      management of a wide range of infection control procedures, in particular the
      decontamination of dental instruments, was collected by interview and by
      examination of practice documentation. This study found that although the
      majority of surgeries (70%) claimed to have a management policy on infection
      control, only 50% of these were documented. For infection control policies, 79%
      of surgeries had access to the British Dental Association Advice Sheet A12.
      Infection control policies were claimed to be present in 89% of surgeries, of
      which 62% were documented. Seventy-seven per cent of staff claimed to have
      received specific infection control training, but for instrument decontamination
      this was provided mainly by demonstration (97%) or observed practice (88%). Many
      dental nurses (74%) and dental practitioners (57%) did not recognise the symbol
      used to designate a single-use device. Audit of infection control or
      decontamination activities was undertaken in 11% of surgeries. The majority of
      surgeries have policies and procedures for the management of infection control in
      dental practice, but in many instances these are not documented. The training of
      staff in infection control and its documentation is poorly managed and
      consideration should be given to development of quality management systems for
      use in dental practice.

PMID- 19162376
TI  - Before and after the trauma bay: the prevention of violent injury among youth.
AB  - Despite a decline in the incidence of homicide in recent years, the United States
      retains the highest youth homicide rate among the 26 wealthiest nations. Homicide
      is the second leading cause of death overall and the leading cause of death for
      male blacks aged 15 to 24 years. High rates of health care recidivism for violent
      injury, along with increasing research that demonstrates the effectiveness of
      violence prevention strategies in other arenas, dictate that physicians recognize
      violence as a complex preventable health problem and implement violence
      prevention activities into current practice rather than relegating violence
      prevention to the criminal justice arena. The emergency department (ED) and
      trauma center settings in many ways are uniquely positioned for this role.
      Exposure to firearm violence doubles the probability that a youth will commit
      violence within 2 years, and research shows that retaliatory injury risk among
      violent youth victims is 88 times higher than among those who were never exposed
      to violence. This article reviews the potential role of the ED in the prevention
      of youth violence, as well as the growing number of ED- and hospital-based
      violence prevention programs already in place.

PMID- 19162377
TI  - Seasonality of Bacillus species isolated from blood cultures and its potential
      implications.
AB  - BACKGROUND: Because they are rarely associated with actual infections, Bacillus
      species are usually defined as contaminants. However, when isolated, they require
      precise laboratory identification and may influence treatment. METHODS: Our aims
      were to examine the seasonality of Bacillus spp isolates cultured from clinical
      blood specimens. Blood culture results of several hospitals between December 1,
      2003, and October 31, 2007, were analyzed. The data were aggregated by month of
      isolation and were also studied by age. Spectral and Cosinor analyses were used
      to examine the periodicity of the bacillus isolates. RESULTS: Of 931,331 blood
      cultures analyzed, 2487 (1.7%) yielded Bacillus spp isolates. There was a 2.5
      fold increase in the number of bacillus isolates during August to October,
      compared with the other months (P < .01). This finding was consistent over
      hospitals and in all age groups. Spectral and Cosinor analyses confirmed this
      pattern. CONCLUSION: Isolation of Bacillus spp from blood cultures has a seasonal
      pattern. This observation needs to be taken into account in surveillance systems
      for early detection of anthrax and in investigating nosocomial outbreaks.
      Elucidating the cause of this seasonality may enable future reduction in
      contamination rates.

PMID- 19162378
TI  - NETNEP 2008 special edition.

PMID- 19162379
TI  - Uncertainty of block estimates introduced by mis-allocation of point samples: on
      the example of spatial indoor Radon data.
AB  - The European indoor Radon map which is currently under production is based on
      gridded data supplied by the contributing countries. Each grid node represents
      the arithmetic mean (among other statistics) of the individual measurements
      within 10 x 10 km(2), called cells, pixels or blocks, which are aligned to a
      common metric coordinate system. During work the question emerged, if uncertainty
      in the geo-referencing of individual data might affect the aggregated "block"
      statistics to an extent that the statistics have an unpredictably high additional
      uncertainty, which makes them unusable. In this note we try to quantify the
      effect, based on simulations. The overall result is that the relevant statistics
      should not be affected too badly in most cases, in particular if the rate of mis
      allocations, and the mean uncertainty of coordinates are not too high, so that
      also cell statistics which are to some degree distorted by mis-allocated data,
      can still be used for the purpose of the European Radon map.

PMID- 19162380
TI  - The influence of hot particle contamination on (90)Sr and (137)Cs transfers to
      milk and on time-integrated ingestion doses.
AB  - Most models for transfers of radionuclides through the food chain typically
      assume that the radioactivity is initially deposited in chemically available
      forms. It is known, however, that releases of radionuclides in the form of hot
      particles may significantly influence their environmental transfers and uptake to
      the food chain. This study presents models for time changes in (90)Sr and (137)Cs
      in milk which incorporate hot particle contamination using observed rates of hot
      particle dissolution following the Chernobyl accident. A general equation is
      presented for the influence of hot particles on overall ingestion doses. As
      expected from previous work, fallout of hot particles significantly influences
      time changes in radionuclide activity concentrations in foodstuffs. It is also
      shown that incorporation of radionuclides in hot particles influences time
      integrated ingestion doses. For a situation in which a large proportion (90-100%)
      of fallout is in slowly dissolving hot particles, time-integrated ingestion doses
      from (90)Sr and (137)Cs are reduced by a factor of approximately two compared to
      the case where all radioactivity is deposited in bioavailable forms. However, the
      influence of rapidly dissolving hot particles on time-integrated ingestion doses
      is relatively minor. Remaining significant uncertainties in dose estimates are
      discussed.

PMID- 19162381
TI  - Seasonality of 137Cs in roe deer from Austria and Germany.
AB  - Empirical data on the (137)Cs activity concentration in meat of roe deer
      (Capreolus capreolus) roaming in 3 spruce forest areas and one peat bog area are
      presented and compared. They cover time series of nearly 20 years after a spike
      contamination in 1986 originating from Chernobyl. A model is presented which
      considers three soil compartments to describe the change of the availability of
      (137)Cs with time. The time-dependency of the (137)Cs activity concentration in
      meat of roe deer is a combination of two components: (1) an exponential decay and
      (2) a peak in the second half of each year during the mushroom season. The
      exponential decay over the years can be described by a sum of two exponential
      functions. The additional transfer of (137)Cs into roe deer during the mushroom
      season depends on precipitation. On the peat bog the (137)Cs activity
      concentration in roe deer is higher and more persistent than in spruce forest.

PMID- 19162382
TI  - The role of bronchoscopy and gastroscopy in intraoral minor salivary gland
      carcinomas at initial staging.
AB  - Intraoral minor salivary gland carcinomas are rare tumours the incidence,
      distribution, and prognostic factors of which differ. The prognosis of patients
      depends on the presence of metastases or synchronous malignant diseases that
      usually affect the lungs. The incidence of metastases has been reported to be
      about 9% at the time of primary staging. The aim of this study was to assess the
      value of bronchoscopy and gastroscopy in the routine staging of minor salivary
      gland cancers. We retrospectively reviewed the casenotes of 95 patients who had
      presented with newly diagnosed intraoral minor salivary gland carcinomas. Data
      were collected about abnormalities detected during endoscopic screening; a biopsy
      was taken if reasonable and if the resulting diagnosis influenced the planned
      treatment. Thirty-eight patients with abnormalities were detected (40%); 31
      diagnoses were confirmed by bronchoscopy and 44 by gastroscopy. Bronchoscopy
      confirmed a total of 6 malignancies: 4 were synchronous carcinomas of the lung
      and 2 metastases of the primary tumour. One oesophageal cancer was detected by
      gastroscopy. The proposed treatment was affected in five of these seven. For
      therapeutic, diagnostic, and prognostic reasons bronchoscopy and gastroscopy
      should be included routinely into staging of intraoral minor salivary gland
      carcinomas.

PMID- 19162383
TI  - "Informed" consent in adult patients: can we achieve a gold standard?
AB  - In maxillofacial surgery the removal of mandibular third molars (wisdom teeth)
      attracts more litigation than any other procedure. The amount of information
      required for a patient to give valid consent is well-known, but there is no "gold
      standard" currently accepted. We aimed to define the components of such a gold
      standard and apply them to a group of patients. An audit was then made of the
      patients' recall and understanding of the process. The gold standard was only
      partially met in most cases, yet most patients felt that the process had been
      appropriate to their needs. Obtaining informed consent for the removal of
      mandibular third molars is difficult.

PMID- 19162384
TI  - Risk assessment of inorganic arsenic pollution on human health.

PMID- 19162385
TI  - Triphenyltin alters lipid homeostasis in females of the ramshorn snail Marisa
      cornuarietis.
AB  - Molluscs are sensitive species to the toxic effects of organotin compounds,
      particularly to masculinisation. Both tributyltin (TBT) and triphenyltin (TPT)
      have been recently shown to bind to mollusc retinoid X receptor (RXR). If RXR is
      involved in lipid homeostasis, exposure to TPT would have an immediate effect on
      endogenous lipids. To test this hypothesis, the ramshorn snail Marisa
      cornuarietis was exposed to environmentally relevant concentrations of TPT (30,
      125, 500 ng/L as Sn) in a semi-static water regime for 7 days. Percentage of
      lipids and total fatty acid content decreased significantly in TPT-exposed
      females while the activity of peroxisomal acyl-CoA oxidase, involved in fatty
      acid catabolism, increased. In addition, fatty acid profiles (carbon chain length
      and unsaturation degree) were significantly altered in exposed females but not in
      males. This work highlights the ability of TPT to disrupt lipid metabolism in M.
      cornuarietis at environmentally realistic concentrations and the higher
      susceptibility of females in comparison to males.

PMID- 19162386
TI  - The effects of trust in physician on self-efficacy, adherence and diabetes
      outcomes.
AB  - Trust in physicians has been associated with a range of patient behaviors.
      However, previous research has not focused on the mechanisms by which trust
      affects health outcomes and mostly has made use of self-rated health. This study
      tested a theoretical model of variables influencing the relations of trust to
      both objective and self-rated health. We hypothesized that patients who trust
      their physicians more were likely to have stronger self-efficacy and outcome
      expectations. We expected this, in turn, to be associated with better treatment
      adherence and objective health outcomes. In addition, we hypothesized that highly
      trusting patients would be more likely to report better health status through
      enhanced self-efficacy. Data for this research came from a sample of 480 adult
      patients with type 2 diabetes in Taiwan. Patients completed measures of trust,
      self-efficacy, outcome expectations, adherence, and the SF-12 health survey.
      Objective outcomes, including body mass index, glycosylated hemoglobin, blood
      lipid, and diabetes-related complications, were assessed by follow-up chart
      review. The structural equation analyses which were implemented by LISREL VIII
      resulted in a proper solution that exhibited adequate fit. All hypothesized paths
      were statistically significant and in the predicted directions. The mediation
      roles of self-efficacy and outcome expectations were further confirmed by the
      results of structural equation modeling and bootstrap analyses. In the
      multivariate regression, although the relations of patient trust to blood lipid
      and self-rated health were confirmed, the direct link of trust to glycosylated
      hemoglobin was only significant in the bivariate model. This study clarifies the
      association of trust with different types of health outcomes and provides the
      empirical evidence that trust in physicians is associated with both self-rated
      health and therapeutic response. However, a more longitudinal study design is
      necessary to precisely determine both the strength and causality of these
      relationships.

PMID- 19162387
TI  - Public ideas and values concerning the commercialization of organ donation in
      four European countries.
AB  - Against the background of the increasing academic and political debate on
      financial incentives for organ donation, we conducted a qualitative investigation
      on the conditions under which European citizens would actually consider or refuse
      financial incentives for organ donation. Our paper combines an analysis of data
      that were collected in eight Focus Group discussions on transplantation medicine
      with lay people and patients from four European countries (Cyprus, Germany, the
      Netherlands, and Sweden) with a critical re-assessment of the dichotomy between
      gift and commodity in the recent political and academic discourse. We find that
      the distinction between living and post mortem donation on the one hand, and
      between different models of financial incentives on the other, plays a crucial
      role for the participants' values and ideas about organ donation. We discuss the
      significance of our results with particular respect to the central role of
      reciprocity and draw conclusions for the bioethical and biopolitical debate.

PMID- 19162388
TI  - Problems inhibiting attentional capture by irrelevant stimuli in patients with
      frontotemporal dementia.
AB  - We studied the role of the frontal lobes in orienting spatial attention and
      inhibiting attentional capture by goal-irrelevant stimuli, using a spatial cueing
      method in patients with frontotemporal dementia (FTD). Two blocks of trials were
      presented, one with non-predictive cues and the other with counter-predictive
      cues. FTD patients showed a global orienting deficit, with a greater difference
      between invalid and valid trials than age-matched controls. However, they were
      able to use the (counter-) predictiveness of the cue to reduce the invalid/valid
      difference when targets occurred most often in the location opposite the cue.
      Thus, endogenous control of attention in our FTD patients was sufficient to
      reorient attention on the basis of the probability of events, but not to resist
      the capture of attention by goal-irrelevant stimuli. These results confirm the
      role of frontal lobes in the inhibition of attentional capture.

PMID- 19162390
TI  - Quantitative evaluation of respiration induced metabolic oscillations in
      erythrocytes.
AB  - The changes in the partial pressures of oxygen and carbon dioxide (P(O(2)) and
      P(CO(2))) during blood circulation alter erythrocyte metabolism, hereby causing
      flux changes between oxygenated and deoxygenated blood. In the study we have
      modeled this effect by extending the comprehensive kinetic model by Mulquiney and
      Kuchel [P.J. Mulquiney, and P.W. Kuchel. Model of 2,3-bisphosphoglycerate
      metabolism in the human erythrocyte based on detailed enzyme kinetic equations:
      equations and parameter refinement, Biochem. J. 1999, 342, 581-596.] with a
      kinetic model of hemoglobin oxy-/deoxygenation transition based on an oxygen
      dissociation model developed by Dash and Bassingthwaighte [R. Dash, and J.
      Bassingthwaighte. Blood HbO(2) and HbCO(2) dissociation curves at varied O(2),
      CO(2), pH, 2,3-DPG and temperature levels, Ann. Biomed. Eng., 2004, 32(12), 1676
      1693.]. The system has been studied during transitions from the arterial to the
      venous phases by simply forcing P(O(2)) and P(CO(2)) to follow the physiological
      values of venous and arterial blood. The investigations show that the system
      passively follows a limit cycle driven by the forced oscillations of P(O(2)) and
      is thus inadequately described solely by steady state consideration. The
      metabolic system exhibits a broad distribution of time scales. Relaxations of
      modes with hemoglobin and Mg(2+) binding reactions are very fast, while modes
      involving glycolytic, membrane transport and 2,3-BPG shunt reactions are much
      slower. Incomplete slow mode relaxations during the 60 s period of the forced
      transitions cause significant overshoots of important fluxes and metabolite
      concentrations - notably ATP, 2,3-BPG, and Mg(2+). The overshoot phenomenon
      arises in consequence of a periodical forcing and is likely to be widespread in
      nature - warranting a special consideration for relevant systems.

PMID- 19162389
TI  - The somatotopy of speech: phonation and articulation in the human motor cortex.
AB  - A sizable literature on the neuroimaging of speech production has reliably shown
      activations in the orofacial region of the primary motor cortex. These
      activations have invariably been interpreted as reflecting "mouth" functioning
      and thus articulation. We used functional magnetic resonance imaging to compare
      an overt speech task with tongue movement, lip movement, and vowel phonation. The
      results showed that the strongest motor activation for speech was the somatotopic
      larynx area of the motor cortex, thus reflecting the significant contribution of
      phonation to speech production. In order to analyze further the phonatory
      component of speech, we performed a voxel-based meta-analysis of neuroimaging
      studies of syllable-singing (11 studies) and compared the results with a
      previously-published meta-analysis of oral reading (11 studies), showing again a
      strong overlap in the larynx motor area. Overall, these findings highlight the
      under-recognized presence of phonation in imaging studies of speech production,
      and support the role of the larynx motor cortex in mediating the "melodicity" of
      speech.

PMID- 19162391
TI  - Hydrogen bonding versus stacking stabilization by modified nucleobases
      incorporated in PNA.DNA duplexes.
AB  - The effects of incorporation of the modified nucleobases, 2,6-diaminopurine (D)
      (substituting for adenine) and 7-chloro-1,8-naphthyridin-2-(1H)-one (bicyclic
      thymine, bT) (substituting for thymine), that stabilize PNA.DNA duplex formation
      by increasing hydrogen bonding and/or base pair stacking interactions have been
      studied by thermal denaturation in terms of thermodynamics. Although the
      stabilizing effect of the bT base (in contrast to that of D base) is abolished
      upon addition of dimethyl formamide, thereby indicating that the stabilization is
      predominantly due to hydrophobic stacking forces, duplex stabilization was found
      to be enthalpic for both nucleobases. Increased stabilization (although not fully
      linearly) was observed with increasing numbers of modified bases, and single base
      sequence discrimination was only slightly compromised, but showed significant
      dependence on the sequence context.

PMID- 19162392
TI  - Effect of quinone on the fluorescence decay dynamics of endogenous flavin bound
      to bacterial luciferase.
AB  - The interaction of quinone with luciferase from Photobacterium leiognathi was
      studied based on the fluorescence decay measurements of the endogenous flavin
      bound to the enzyme. Homologous 1,4-quinones, 1,4-benzoquinone, methyl-1,4
      benzoquinone, 2-methyl-5-isopropyl-1,4-benzoquine and 1,4-naphthoquinone, were
      investigated. In the absence of quinone, the fluorescence intensity and
      anisotropy decays of the endogenous flavin exhibited two intensity decay
      lifetimes (~1 and 5 ns) and two anisotropy decay lifetimes (~0.2 and 20 ns),
      suggesting a heterogeneous quenching and a rotational mobility microenvironment
      of the active site of the luciferase, respectively. In the presence of quinone,
      the intensity decay heterogeneity was largely maintained, whereas the fraction of
      the short anisotropy decay component and the averaged rotational rate of FMN
      increased with the increasing hydrophobicity of the quinone. We hypothesize that
      the hydrophobicity of the quinone plays a role in the non-specific inhibition
      mechanism of xenobiotic molecules in the bacterial bioluminescence system via
      altering the rotational mobility of the endogenous flavin in the luciferase.

PMID- 19162393
TI  - Functional phenotyping and genotyping of circulating tumor cells from patients
      with castration resistant prostate cancer.
AB  - Circulating tumor cells (CTCs) hold promise for studying advanced prostate
      cancer. A functional collagen adhesion matrix (CAM) assay was used to enrich CTCs
      from prostate cancer patients' blood. CAM ingestion and epithelial immuno
      staining identified CTCs, which were genotyped using oligonucleotide array
      comparative genomic hybridization. The highest CTC counts were observed in men
      with metastatic castration resistant prostate cancer (CRPC) compared to
      castration sensitive prostate cancer. Copy number profiles for CRPC CTCs were
      similar to paired solid tumor DNA, and distinct from corresponding DNA from the
      residual CAM-depleted blood. CAM CTC enrichment may allow cellular and genetic
      analyses in prostate cancer.

PMID- 19162394
TI  - Evaluation of laboratory and industrial meat and bone meal combustion residue as
      cadmium immobilizing material for remediation of polluted aqueous solutions:
      "chemical and ecotoxicological studies".
AB  - Meat and Bone Meals (MBM) combustion residues (ashes) are calcium and phosphate
      rich materials. The aim of this work is to evaluate ashes efficiency for
      remediation of cadmium-contaminated aqueous solutions, and to assess the
      bioavailability of cadmium on Xenopus laevis larvae. In this study both
      industrial (MBM-BA) and laboratory (MBM-LA) ashes are compared regarding their
      efficiency. Kinetic investigations reveal that cadmium ions are quickly
      immobilized, with a maximum cadmium uptake at 57 mg Cd(2+)/g of ashes for MBM-LA,
      two times higher than metal uptake quantity of MBM-BA, in our experimental
      conditions. Chemical and X-ray diffraction analysis (XRD) reveal that Cd(2+) is
      mainly immobilized as Ca(10-x)Cd(x)(PO(4))(6)(OH)(2) by both ashes, whereas
      otavite, Cd(CO(3)), is also involved for MBM-LA in cadmium uptake. Otavite
      formation could be explained by the presence of carbonates in MBM-LA, as observed
      by IR. Genotoxicity of cadmium solution on Xenopus larvae is observed at 0.02,
      0.2 and 2mg Cd(2+)/L. However addition of only 0.1g/L MBM-LA inhibits these
      effects for the above concentration values whereas Cd(2+) bioaccumulation in
      larvae's liver is similar for both experiments, with and without ashes.

PMID- 19162395
TI  - A coherence approach to phase-contrast microscopy II: experiment.
AB  - We report an experimental investigation of the optical transfer functions for an
      X-ray microscope operated in defocus phase-contrast mode. The results are
      compared with a theoretical model of partially coherent image formation and are
      found to be in excellent agreement.

PMID- 19162396
TI  - Grain boundary enrichment in the FePt polymorphic A1 to L1(0) phase
      transformation.
AB  - A series of Fe(54+/-1)Pt(46+/-1) thin films have been sputter-deposited and
      annealed at various times and temperatures to facilitate the A1 to L1(0)
      polymorphic phase transformation. The annealing times span one minute to tens of
      minutes over temperatures of 300-800 degrees C. The films were characterized by X
      ray and electron diffraction and atom probe tomography. This time-temperature
      regime provides 'snap-shots' into the compositional segregation evolution at the
      grain boundaries during the polymorphic phase transformation. The as-deposited A1
      phase showed a preferential segregation of Pt to the grain boundaries. The
      reduction of Pt enrichment at the boundaries was observed for all L1(0) ordered
      films.

PMID- 19162397
TI  - Failure mechanisms of silicon-based atom-probe tips.
AB  - Atom-probe (AP) analysis of silicon based samples frequently fail due to rupture
      of the tip. We have investigated the stability and failure mechanisms of silicon
      tips when prepared for AP analysis via Focused Ion Beam (FIB) milling. We
      observed four mechanisms that commonly lead to failure of the tips. These
      mechanisms are a deformation of the tips apex due to an interaction between the
      oxidized amorphous layer and induced mechanical vibrations, a rip off of an
      isolating oxide-layer, the rip off of a cap layer due to insufficient adhesion
      and a failure of the tip in the course of the analysis due to the rising voltage
      applied to the tip. In this paper we will discuss all four mechanisms show
      evidence of the causes of the breakdown and discuss options that allow avoiding
      tip failure.

PMID- 19162398
TI  - A high-speed area detector for novel imaging techniques in a scanning
      transmission electron microscope.
AB  - A scanning transmission electron microscope (STEM) produces a convergent beam
      electron diffraction pattern at each position of a raster scan with a focused
      electron beam, but recording this information poses major challenges for
      gathering and storing such large data sets in a timely manner and with sufficient
      dynamic range. To investigate the crystalline structure of materials, a 16x16
      analog pixel array detector (PAD) is used to replace the traditional detectors
      and retain the diffraction information at every STEM raster position. The PAD,
      unlike a charge-coupled device (CCD) or photomultiplier tube (PMT), directly
      images 120-200keV electrons with relatively little radiation damage, exhibits no
      afterglow and limits crosstalk between adjacent pixels. Traditional STEM imaging
      modes can still be performed by the PAD with a 1.1kHz frame rate, which allows
      post-acquisition control over imaging conditions and enables novel imaging
      techniques based on the retained crystalline information. Techniques for rapid,
      semi-automatic crystal grain segmentation with sub-nanometer resolution are
      described using cross-correlation, sub-region integration, and other post
      processing methods.

PMID- 19162399
TI  - Field emission studies on electrochemically synthesized ZnO nanowires.
AB  - Nanocrystalline zinc oxide (ZnO) films were synthesized using cathodic reduction
      of Zn foil in aqueous electrolyte of different molar concentrations containing
      ZnCl(2) and H(2)O(2), followed by annealing at 400 degrees C in air. An X-ray
      diffractometer (XRD), scanning electron microscope (SEM) and transmission
      electron microscope (TEM) were used for characterization. The XRD patterns
      exhibited a set of well-defined diffraction peaks corresponding to the wurtzite
      phase of ZnO. SEM and TEM images clearly revealed the formation of randomly
      oriented ZnO nanowires having lengths of several microns and diameters less than
      100nm. From the field emission studies, the threshold field values, required to
      draw emission current density of approximately 1microA/cm(2) were found to be
      1.44, 1.36 and 1.5V/mum for nanowires synthesized using 0.002, 0.004 and 0.016M
      electrolyte concentrations, respectively. All Folwer-Nordheim (F-N) plots showed
      non-linear behavior indicating semiconducting nature of the emitters. The ZnO
      nanowires exhibited good emission current stability at the pre-set value of
      approximately 10microA over a duration of 6h. The simplicity of the synthesis
      route coupled with the promising emission properties made the electrochemically
      synthesized ZnO nanowires a suitable candidate for high-current density
      applications.

PMID- 19162400
TI  - 3DAP analysis of (Ga,Mn)As diluted magnetic semiconductor thin film.
AB  - The distribution of Mn in a Ga(0.963)Mn(0.037)As ferromagnetic semiconductor film
      has been characterized by the three-dimensional atom probe (3DAP) technique. Atom
      probe specimens were directly prepared from the (Ga,Mn)As film grown epitaxially
      on a p-type GaAs substrate by the lift-out technique using a scanning electron
      microscope/focused ion beam system. The atom probe elemental map revealed that
      the Mn atoms in the Ga(0.963)Mn(0.037)As are uniformly dissolved without forming
      any nanometer-sized clusters.

PMID- 19162401
TI  - QD as a bifunctional cell-surface marker for both fluorescence and atomic force
      microscopy.
AB  - Fluorescent quantum dots (QDs) are a new class of fluorescent label and have been
      extensively used in cell imaging. Streptavidin-conjugated QDs have a diameter of
      ca. 10-15 nm; therefore when used as probes to label cell-surface biomolecules,
      they can provide contrast enhancement under atomic force microscopy (AFM) and
      allow specific proteins to be distinguished from the background. In addition, the
      size and fluorescent properties potentially make them as probes in correlative
      fluorescence microscopy (FM) and AFM. In this study, we tested the feasibility of
      using QD-streptavidin conjugates as probes to label wheat germ agglutinin (WGA)
      receptors on the membrane of human red blood cells (RBCs) and simultaneously
      obtain fluorescence and AFM images. The results show that the distribution of QDs
      labeled on human RBCs was non-uniform and that the number of labeled QDs on
      different erythrocytes varied significantly, which perhaps indicates different
      ages of the erythrocytes. Thus, QDs may be employed as bifunctional cell-surface
      markers for both FM and AFM to quantitatively investigate the distribution and
      expression of membrane proteins or receptors on cell surface.

PMID- 19162402
TI  - Positive effect of natural pre-ageing on precipitation hardening in Al-0.44at% Mg
      0.38at% Si alloy.
AB  - Age hardening in a purely ternary Al-Mg0.4-Si0.4 (0.44 at% Mg, 0.38at%Si) alloy
      that is similar to AA6060 was investigated by hardness measurement, TEM and three
      dimensional atom probe (3D-AP). In particular, the effect of natural pre-ageing
      before artificial ageing, which is known to have a positive effect in this alloy,
      was studied by comparing three different conditions: natural ageing only,
      artificial ageing for 1.5h at 180 degrees C only and combined natural pre-ageing
      and subsequent artificial ageing for 1.5h at 180 degrees C. Natural ageing
      influences the mechanical properties significantly. Naturally aged alloys exhibit
      a hardening response that is governed by the presence of small clusters.
      Subsequent artificial ageing of naturally aged specimens increases the value of
      peak hardness, which is attributed to the increase of the number density of
      needle-shaped precipitates as compared to the samples without natural ageing. It
      is assumed that besides these precipitates, the small Si clusters formed at room
      temperature storage remain stable during artificial ageing.

PMID- 19162403
TI  - Establishing an indirect sandwich enzyme-linked-immunosorbent-assay (ELISA) for
      the detection of antibodies against Histomonas meleagridis from experimentally
      infected specific pathogen-free chickens and turkeys.
AB  - No serological method suitable for large screening of antibodies against
      Histomonas meleagridis in poultry is available so far, the objective targeted in
      the present investigation. Consequently, an ELISA was developed as a suitable
      tool for this purpose. Investigating serum samples from non-infected specific
      pathogen-free (spf) chickens and commercial turkeys a high-background signal was
      noticed when ELISA plates were directly coated with purified parasitic cells.
      This signal was significantly reduced by coating the plates with a polyclonal
      rabbit antibody, raised against histomonads, prior to the addition of the
      antigen. Adopting this approach five antigen preparations were compared and a
      high reproducibility could be demonstrated reflected by a very low coefficient of
      variation of 5.3% and 1.7% for the chicken and turkey sera, respectively. After
      this initial development all further experiments were carried out with one set of
      plates and the same antigen preparation. Investigating chicken sera obtained from
      birds infected at 14 days of life, OD values above a predetermined cut-off value
      were observed 2 weeks post-infection and a rise of IgG antibodies was noticed
      until 6 weeks post-infection, when the experiment was terminated. Non-protected
      turkeys infected at 6 weeks of age displayed an increasing IgG response until 14
      days post-infection, prior to the death of animals due to histomonosis. In
      comparison, the majority of turkeys vaccinated with attenuated histomonads,
      obtained through prolonged passaging and challenged 4 weeks later with virulent
      parasites, displayed a demonstrable antibody response after the challenge only.
      Antibody titres increased until 4 weeks post-challenge when the birds were killed
      and the study was terminated. Altogether, the developed indirect sandwich ELISA
      proved to be a quick and efficient method to detect IgG antibodies against H.
      meleagridis in sera of experimentally infected chickens and turkeys and will be a
      helpful tool to obtain more insights into the epidemiology of the parasite and
      the immune response of its hosts.

PMID- 19162404
TI  - Reponse to comment on article by Eligio-Garcia et al. Frequency of Giardia
      intestinalis assemblages isolated from dogs and humans in a community from
      Culiacan, Sinaloa, Mexico using B-giardin restriction gene.

PMID- 19162406
TI  - Family history of alcohol abuse moderates effectiveness of a group motivational
      enhancement intervention in college women.
AB  - This study examined whether a self-reported family history of alcohol abuse (FH+)
      moderated the effects of a female-specific group motivational enhancement
      intervention with first-year college women. First-year college women (N=287)
      completed an initial questionnaire and attended an intervention (n=161) or
      control (n=126) group session, of which 118 reported FH+. Repeated measures
      ANCOVA models were estimated to investigate whether the effectiveness of the
      intervention varied as a function of one's reported family history of alcohol
      abuse. Results revealed that family history of alcohol abuse moderated
      intervention efficacy. Although the intervention was effective in producing less
      risky drinking relative to controls, among those participants who received the
      intervention, FH+ women drank less across five weeks of follow-up than FH- women.
      The current findings provide preliminary support for the differential
      effectiveness of motivational enhancement interventions with FH+ women.

PMID- 19162407
TI  - Forcible, drug-facilitated, and incapacitated rape in relation to substance use
      problems: results from a national sample of college women.
AB  - This is the first study to examine the relation between rape and substance use
      problems in college women as a function of three legally recognized forms of
      rape: forcible, incapacitated, and substance-facilitated rape. Data were
      collected via structured telephone interview with a large national sample of
      college women aged 18-34 years (n=1980). Lifetime prevalence of any type of rape
      was 11.3% in the sample. Prevalence estimates for binge drinking and substance
      abuse were 15.8% and 19.8%, respectively. Lifetime experience of incapacitated
      rape and drug-alcohol facilitated rape, but not forcible rape, were associated
      with increased odds of past-year binge drinking and substance abuse. Findings
      have implications for secondary prevention and call for continued differentiation
      in assessment of rape type.

PMID- 19162408
TI  - Implementation of a smoking cessation treatment integrity protocol: treatment
      discriminability, potency and manual adherence.
AB  - Testing manual adherence and treatment discriminability and potency have become
      increasingly important to ensuring the internal validity of treatment studies
      [Moncher, F.J., & Prinz, R.J., (1991). Treatment fidelity in outcome studies.
      Clinical Psychology Review, 11, 247-266.]. The objective of this study was
      therefore to implement the treatment integrity protocol based on the standardized
      framework proposed by Waltz, Addis, Koerner and Jacobson [Waltz, J., Addis, M.E.,
      Koerner, K., & Jacobson, N.S., (1993). Testing the integrity of a psychotherapy
      protocol: Assessment of adherence and competence. Journal of Consulting and
      Clinical Psychology, 61, 620-630.] to assess manual adherence and treatment
      discriminability and potency in a smoking cessation trial. Audio recordings of
      15, 6-week smoking cessation groups were randomly selected from a sample of 31
      groups and were rated for treatment integrity. Findings offered partial evidence
      for manual adherence which did not differ according to treatment condition.
      Analyses also indicated that the treatments were potent yet not highly
      discriminable across conditions. Despite some challenges, this preliminary
      application of the Waltz et al. [Waltz, J., Addis, M.E., Koerner, K., & Jacobson,
      N.S., (1993). Testing the integrity of a psychotherapy protocol: Assessment of
      adherence and competence. Journal of Consulting and Clinical Psychology, 61, 620
      630.] protocol indicated that it is a promising and flexible tool that may be
      used to examine different aspects of treatment integrity.

PMID- 19162409
TI  - Predicting alcohol use with a recoding-free variant of the Implicit Association
      Test.
AB  - Recently, a modified version of the Implicit Association Test (IAT), the IAT-RF
      (IAT-Recoding Free) was developed which prevents recoding processes by switching
      response assignments randomly between trials rather than between blocks. In this
      study, the IAT-RF was used to measure and examine the predictive validity of
      recoding-free implicit alcohol associations with positive arousal. Findings with
      the IAT-RF demonstrated that alcohol was overall more strongly associated with
      negative sedation than with positive arousal. However, more importantly, the size
      of this compatibility effect was positively correlated with alcohol use
      indicating that stronger implicit alcohol associations with positive arousal are
      related to increased drinking. Further, implicit alcohol associations with
      positive arousal measured with the IAT-RF also predicted unique variance in
      alcohol use above the variance explained by explicit measures. Hence, the present
      findings suggest that implicit associations with positive arousal may play an
      important role in drinking behavior, and demonstrate the validity of the IAT-RF
      as a measure of implicit alcohol associations.

PMID- 19162410
TI  - How can we distract the immune system so that it won't reject transplants? The
      answer: by stimulating the immune response before the transplant.

PMID- 19162411
TI  - Insulin resistance and therapy: cross-talk between phosphatidylinositol-3 kinase
      and mitogen-activated protein kinase pathways.

PMID- 19162412
TI  - Pain reactivity and recovery in preterm neonates: latency, magnitude, and
      duration of behavioral responses.
AB  - BACKGROUND: Studies on acute-procedural pain in neonates have been based more on
      single behavioral scores than on response patterns. AIM: To assess the individual
      reactivity and recovery pattern to the painful procedure of blood collection.
      STUDY DESIGN: A cross-sectional, within-group comparison trial. SUBJECTS: Forty
      eight preterm and very low birth weight neonates hospitalized in a Neonatal
      Intensive Care Unit. OUTCOME MEASURES: The assessment was divided into five
      consecutive phases: Baseline (BL); Antisepsis (A), covering the period of
      handling of the neonate for antisepsis prior to puncture; Puncture (P); Recovery
      Dressing (RD), covering the period of handling of the neonate for dressing until
      positioning for rest in the isolette; and Recovery-Resting (RR). Facial activity
      was recorded by video, and sleep-wake state was recorded at the bedside. The
      facial activity of the neonates was analyzed according to Neonatal Facial Coding
      System (NFCS). The pain reactivity pattern was analyzed using the measures of
      latency, magnitude, and duration of behavioral responses and by comparison
      between the different phases. RESULTS: In the Antisepsis phase, the neonates
      showed higher NFCS score and behavioral arousal than at Baseline. In the Puncture
      phase, the neonates showed higher NFCS score and behavioral activation than in
      Baseline and in Antisepsis. In Recovery-Dressing, 31% of neonates continued to
      show more behavioral activation than at Baseline. CONCLUSION: To better assess
      and manage pain in preterm neonates, it is relevant to analyze the individual
      patterns of changes, focusing on the reactivity and also the recovery, during
      painful stimuli.

PMID- 19162413
TI  - Is term newborn body composition being achieved postnatally in preterm infants?
AB  - BACKGROUND: The American Academy of Pediatrics (AAP) recommends that preterm
      infants' growth duplicates fetal growth rates and that body composition
      replicates in utero body composition. AIMS: To compare the total body fat mass
      between preterm infants assessed at term corrected age and full-term newborns,
      and to investigate the effects of gestational age, gender, weight increase, being
      breast fed on total adiposity. STUDY DESIGN: Prospective observational study.
      SUBJECTS: One hundred and ten preterm infants [mean (SD) gestational age: 29.9
      (2.3) weeks; birth weight: 1118 (274) g], and 87 full term [mean (SD) 38.6 (1.21)
      weeks, 3203 (385) g], breastfed infants. OUTCOME MEASURES: Growth and body
      composition by means of a pediatric air displacement system were assessed at term
      corrected age in preterm infants and on day 3 of life in full term infants.
      RESULTS: Weight, length and head circumference were smaller in the preterm group
      as compared to the term group. Mean (SD) percentage of fat mass in preterm
      infants was significantly higher as compared to term infants [14.8 (4.4) vs 8.59
      (3.71), P<0.0001]. Fat mass was negatively correlated with gestational age
      (P<0.001), and positively associated with weight increase (P< 0.05). CONCLUSIONS:
      Our data suggest that body composition, in terms of fat mass, in preterm infants
      at term corrected age is different from that of full term newborns.

PMID- 19162414
TI  - Sex differences in the relation between prenatal maternal emotional complaints
      and child outcome.
AB  - BACKGROUND: Sex differences are found in animal studies concerning the
      relationship between prenatal maternal stress and outcome of the offspring. Most
      human studies in this field have not addressed sex differences, although
      differences between boys and girls may elucidate the biochemical as well as
      psychological processes involved. Associations between prenatal maternal
      emotional complaints and behavioural problems of toddlers and preschoolers as
      assessed by both mothers and fathers are studied separately for boys and girls.
      METHODS: Healthy Dutch Caucasian singleton, pregnant women (N=444) answered
      questionnaires about anxiety and depression in every trimester of pregnancy. When
      their children (227 boys, 217 girls) were between 14 and 54 months old, both
      parents reported on their current feelings of depression and anxiety and on the
      behavioural problems of their children. RESULTS: Prenatal maternal emotional
      complaints were found to be associated with child behavioural problems both in
      boys and in girls, but in different ways. Prenatal maternal emotional complaints
      during the first trimester were associated with total and internalizing
      behavioural problems for boys. Emotional complaints during the third trimester
      were associated with total, internalizing, as well as externalizing behavioural
      problems for girls. CONCLUSIONS: Differentiation according to sex and information
      on timing of emotional complaints during pregnancy is needed in studies
      concerning the relation between prenatal maternal emotional complaints and child
      outcome.

PMID- 19162415
TI  - Time related changes in luteal prostaglandin synthesis and steroidogenic capacity
      during pregnancy, normal and antiprogestin induced luteolysis in the bitch.
AB  - In nonpregnant and pregnant dogs the corpora lutea (CL) are the only source of
      progesterone (P4) which shows an almost identical secretion pattern until the
      rapid decrease of P4 prior to parturition. For the nonpregnant dog clear evidence
      has been obtained that physiological luteal regression is devoid of a functional
      role of the PGF2alpha-system and seems to depend on the provision of StAR. Yet in
      pregnant dogs the rapid prepartal luteal regression, coinciding with an increase
      of PGF2alpha, may be indicative for different regulatory mechanisms. To assess
      this situation and by applying semi-quantitative Real Time (Taq Man) RT-PCR,
      expression patterns were determined for the following factors in CL of pregnant
      and prepartal dogs and of mid-pregnant dogs treated with the antiprogestin
      Aglepristone: cyclooxygenase 2 (Cox2), prostaglandin E2 synthase (PGES),
      prostaglandin F2alpha synthase (PGFS), its receptors (EP2, EP4 an FP), the
      steroidogenic acute regulatory protein (StAR), 3beta-hydroxysteroid-dehydrogenase
      (3betaHSD) and the progesterone receptor (PR). Peripheral plasma P4
      concentrations were determined by RIA. CL were collected via ovariohysterectomy
      from pregnant bitches (n=3-5) on days 8-12 (Group 1, pre-implantation period),
      days 18-25 (Group 2, post-implantation period), days 35-40 (Group 3, mid
      gestation period) and during the prepartal progesterone decline (Group 4).
      Additionally, CL were obtained from groups of 5 mid-pregnant dogs (days 40-45)
      24h, respectively 72h after the second treatment with Aglepristone. Expression of
      Cox2 and PGES was highest during the pre-implantation period, that of PGFS and FP
      during the post-implantation period. EP4 and EP2 revealed a constant expression
      pattern throughout pregnancy with a prepartal upregulation of EP2. 3betaHSD and
      StAR decreased significantly from the pre-implatation period to prepartal
      luteolysis, it was matched by the course of P4 concentrations. Expression of the
      PR was higher during mid-gestation and prepartal luteolysis than in the two
      preceding periods. After application of Aglepristone the overall mRNA-expression
      resembled the situation during prepartal luteolysis except for EP2, which
      remained unchanged. These data suggest that - as in the nonpregnant bitch - also
      in the pregnant bitch luteal production of prostaglandins is associated with
      luteal support rather than luteolysis. On the other hand induction of luteolysis
      by the PR blocker Aglepristone points to a role of luteal P4 as an autocrine
      factor in a positive loop feedback system controlling the availability of P4,
      StAR and 3betaHSD.

PMID- 19162416
TI  - A review of uterine structural modifications that influence conceptus
      implantation and development in sheep and goats.
AB  - Evolution of the placenta and viviparity in eutherian animals underscores the
      need for an intimate relationship between the developing conceptus (embryo/foetus
      and associated extra-embryonic membranes) and the dam throughout the period of
      pregnancy. Thus, maternal support is unequivocally important for conceptus
      survival and development in utero. Under the influence of several pregnancy
      associated hormones, the maternal uterine architecture undergoes rapid growth and
      substantial remodeling early in gestation. These changes are necessary
      preparations to accommodate and support rapid conceptus development and growth in
      the later two-thirds of pregnancy. There are species variations in the nature and
      extent of uterine remodeling during pregnancy. The regulatory influence of these
      uterine wall modifications on conceptus survival, implantation and placentation
      in sheep and goats are discussed in this review.

PMID- 19162417
TI  - Speaker-dependent characteristics of the nasals.
AB  - Investigation on human speaker identification enables us to know the indexical
      cues to speakers, and it may consequently lead to the effective acoustical
      parameters that can be used for forensic speaker recognition. It is known that
      speaker individuality interacts with the phonological or linguistic information
      contained in speech signals. As proof, the accuracy of perceptual speaker
      identification (PSI) performances depends on what types of sounds are presented
      to the listeners. In a series of our previous experiments, we have been
      investigating the effective sounds for PSI, and the stimuli containing a nasal
      were found to be the ones. In this present study, we conducted another PSI
      experiment in order to examine the reproducibility of the nasal effectiveness,
      and to see the effects of the following vowels. Coronal nasals were shown to be
      effective despite the different speaker set or the following vowels, and the
      stimuli containing a nasal were significantly better than those without it. In
      the second part of this paper, we introduce the results of the acoustical
      analysis of the stimuli. The contours of the energy transitions showed variations
      in shape among speakers for all three types of the analysis targets; nasals,
      stops, and fricatives, although the inter-speaker difference in the energy slopes
      for the consonant articulation was significant especially in nasal sounds. We
      also examined the effects of the sampling frequencies and the speech codecs, and
      found that the speaker-dependent shapes of these energy contours were maintained
      as long as the speech materials were uncompressed. The contours of the nasals
      appeared to be stable within a speaker, compared to other types of sounds.

PMID- 19162418
TI  - [Construction-cost assessment of a program designed to promote physical and
      sports activities and prevent doping behaviors: PN-APSD - on 2002-2007].
AB  - BACKGROUND: According to the framework legislation promulgated as part of the
      reform of finance laws in France, quality is a mandatory feature of all
      governmental actions. In this context, this work was conducted to assess the
      construction cost of a national health program designed to promote physical and
      sports activities and prevent doping behaviors. This program was considered to
      have the characteristic features of a successful governmental health
      intervention. METHODS: Four cost categories were evaluated: cost of the activity
      itself, transportation costs, communication costs and promotion costs. RESULTS:
      It was found that the program costs for 2002-2007 were 100,000 euro, with 15% of
      the costs in the communication category. CONCLUSION: Economic elements could be
      associated with factors of successful health service interventions in order to
      help decision makers responsible for the public interest and the consistency of
      public health actions.

PMID- 19162419
TI  - [Linking anonymous databases for national and international multicenter
      epidemiological studies: a cryptographic algorithm].
AB  - BACKGROUND: Compiling individual records which come from different sources
      remains very important for multicenter epidemiological studies, but at the same
      time European directives or other national legislation concerning nominal data
      processing have to be respected. These legal aspects can be satisfied by
      implementing mechanisms that allow anonymization of patient data (such as hashing
      techniques). Moreover, for security reasons, official recommendations suggest
      using different cryptographic keys in combination with a cryptographic hash
      function for each study. Unfortunately, such an anonymization procedure is in
      contradiction with the common requirement in public health and biomedical
      research as it becomes almost impossible to link records from separate data
      collections where the same entity is not referenced in the same way. Solving this
      paradox by using methodology based on the combination of hashing and enciphering
      techniques is the main aim of this article. METHODS: The method relies on one of
      the best known hashing functions (the secure hash algorithm) to ensure the
      anonymity of personal information while providing greater resistance to
      dictionary attacks, combined with encryption techniques. The originality of the
      method relies on the way the combination of hashing and enciphering techniques is
      performed: like in asymmetric encryption, two keys are used but the private key
      depends on the patient's identity. RESULTS: The combination of hashing and
      enciphering techniques provides a great improvement in the overall security of
      the proposed scheme. CONCLUSION: This methodology makes the stored data available
      for use in the field of public health for the benefit of patients, while
      respecting legal security requirements.

PMID- 19162420
TI  - [The European Schizophrenia Outpatient Health Outcomes Study: observational study
      over 36 months of the French cohort of schizophrenic outpatients treated with
      antipsychotics].
AB  - BACKGROUND: Studies describing long-term continuous care of outpatients with
      schizophrenia are relatively scarce. The prospective European Schizophrenia
      Outpatient Health Outcomes study (SOHO) provides data on a cohort of
      schizophrenic patients over a period of three years. METHODS: Prospective, long
      term, observational study including outpatients who initiate therapy or change to
      a new antipsychotic. The study was designed to provide two patient groups of
      approximately equal size: treated either with olanzapine or a non-olanzapine
      antipsychotic. Sociodemographic, clinical and disease characteristics at baseline
      were described. Clinical severity of symptoms was assessed at each visit using
      the Clinical Global Impression scale (CGI). Treatment outcomes were analyzed as
      treatment discontinuation, remission and relapse rates. RESULTS: French results
      are presented in this report. Nine hundred and thirty-three patients (62% males)
      were recruited between March and December 2001. The mean age was 37.1+/-11.5
      years. The mean time since first consultation for schizophrenia was 8.0+/-9.3
      years. At study baseline, one quarter had paid employment, less than one third
      had a spouse or partner and more than half of them had an independent housing.
      Thirty percent of patients reported a previous suicide attempt. The mean CGI was
      4.5+/-1.0 at admission. Overall, medication discontinuation for any cause
      occurred for 42% of patients. A remission (defined by a CGI<or=3 maintained for 6
      months, without hospitalization) was obtained in 63% of patients, 49% of patients
      relapsed (defined as hospitalization or CGI increase reaching 4 or more) during
      the three-year follow-up period. A suicide attempt occurred in 60 patients
      (cumulative proportion 7%). CONCLUSIONS: The clinical findings of the French
      cohort of patients confirmed the high burden of the disease. Identification of
      risk factors for discontinuation of treatment should provide a better
      individualization of patient care and a better impact on the different domains of
      effectiveness.

PMID- 19162421
TI  - [Do non-urgent patients presenting to an emergency department agree with a
      reorientation towards an alternative care department?].
AB  - BACKGROUND: Emergency department (ED) utilization has increased for several
      decades. ED-s are becoming more and more busy because of patients with non-urgent
      problems, and their demand for service has resulted in overcrowding in ED. To
      resolve this problem, primary care units involving general practitioners have
      been established. The objective of this study is to assess provision of the shift
      to other health care facilities for no urgent ED patients, starting from entry to
      ED at the request of the triage nurse. METHODS: A cross-sectional study was
      conducted during a one-week period in the adult ED of La Conception Hospital in
      Marseilles, France. Only no urgent patients identified prospectively by the
      triage nurse were included. Information was gathered regarding the usual source
      of care, reason for the visit, care itinerary before presenting to the ED,
      patient's perception of emergency level, their willingness regarding a
      reorientation to another health care facility, accomplished actions, and type of
      discharge. RESULTS: Among 245 ED patients, 110 were identified as no urgent by
      the triage nurse, and 85 effectively answered questions for the purpose of this
      study. In 76.4% of the cases, the patients were self-referred to ED, however one
      third had contacted a physician. The most common reasons provided for attending
      the ED were pain (55.3%), laboratory and radiographic investigations (37.6%), and
      difficulty in accessing the usual source of care (22.3%). The mean level of
      emergency perception was 10.6+/-5.6 on a zero-twenty scale. Half of the patients
      presented for traumatology concerns. One-third had an additional examination, six
      received treatments, and none were hospitalized. Upon entry to ED, more than two
      thirds of patients accepted the principle of reorientation to another health care
      facility. Two main factors linked with this decision were employment status (odds
      ratio [OR]=4.5; 95% confidence interval [CI]=1.6-12.9) and the perceived
      emergency level (OR=0.88; 95% CI=0.8-0.9). Among patients who refused
      reorientation, 41 of them were able to pay an additional cost to receive care in
      the ED. CONCLUSION: Alternative structures such as primary care units near the ED
      seem to be an appropriate response to meet the growing demand of no urgent
      patients. The success of providing this reorientation, however, could be
      determined by the working hours of the structures and the practice of certain
      technical skills.

PMID- 19162422
TI  - Quantification of artemisinin in human plasma using liquid chromatography coupled
      to tandem mass spectrometry.
AB  - A liquid chromatographic tandem mass spectroscopy method for the quantification
      of artemisinin in human heparinised plasma has been developed and validated. The
      method uses Oasis HLB mu-elution solid phase extraction 96-well plates to
      facilitate a high throughput of 192 samples a day. Artesunate (internal standard)
      in a plasma-water solution was added to plasma (50 microL) before solid phase
      extraction. Artemisinin and its internal standard artesunate were analysed by
      liquid chromatography and MS/MS detection on a Hypersil Gold C18 (100 mm x 2.1
      mm, 5 microm) column using a mobile phase containing acetonitrile-ammonium
      acetate 10mM pH 3.5 (50:50, v/v) at a flow rate of 0.5 mL/min. The method has
      been validated according to published FDA guidelines and showed excellent
      performance. The within-day, between-day and total precisions expressed as
      R.S.D., were lower than 8% at all tested quality control levels including the
      upper and lower limit of quantification. The limit of detection was 0.257 ng/mL
      for artemisinin and the calibration range was 1.03-762 ng/mL using 50 microL
      plasma. The method was free from matrix effects as demonstrated both graphically
      and quantitatively.

PMID- 19162423
TI  - Simultaneous determination of (fluoro)quinolones antibacterials residues in
      bovine milk using ultra performance liquid chromatography-tandem mass
      spectrometry.
AB  - The ultra performance liquid chromatography-tandem mass spectrometry (UPLC)
      method had been developed for 22 (fluoro)quinolone(QNs) antibacterials in milk
      with multiple reaction monitoring (MRM) as acquisition mode. The analytes were
      extracted from the sample using Mcllvaine buffer by ultrasonic bath, and purified
      by solid-phase extraction (SPE) cartridge. The residue were dried under nitrogen
      and dissolved in mobile phase before UPLC-MS/MS final analysis. The calibration
      curve of six concentrations for 22 QNs showed good linearity and the good
      correlation coefficients (r> or =0.9851) were achieved. The limit range of
      quantification was 0.008-0.339microg/kg. The recovery range was 63.1-94.6% except
      flumequine, nalidixic acid and nadifloxacin. The method was precise: the relative
      standard deviations of the method for milk were not more than 13.12%. The
      accuracies and sensitivity of the method were good for simultaneous determination
      of 22 QNs.

PMID- 19162424
TI  - Application of microfluidic gradient chip in the analysis of lung cancer
      chemotherapy resistance.
AB  - The major challenge of chemotherapy is the disease resistance for many lung
      cancer patients. Integrated microfluidic systems offer many desirable
      characteristics and can be used in cellular biological analysis. This work aimed
      to study the correlation between the expression of Glucose Regulated Protein-78
      (GRP78) and the resistance to anticancer drug VP-16 in human lung squamous
      carcinoma cell line SK-MES-1 using an integrated microfluidic gradient chip
      device. We used A23187, a GRP78 inducer, with a gradient concentration in the
      upstream network of the device to induce the expression of GRP78 in the cells
      cultured in the downstream before the addition of VP-16. The expression of GRP78
      was detected by immunofluorescence, the apoptosis for the cells treated by VP-16
      was assessed morphologically by 4',6-diamidino-2-phenylindole (DAPI) staining.
      The results indicated that the expressions of GRP78 increased greatly for the
      cells under the induction of A23187 with a dose-depended manner, while the
      percentage of apoptotic cells decreased significantly after being treated by VP
      16. Our results from this study confirmed the role of GRP78 played in the
      chemotherapy resistance to VP-16 in SK-MES-1 cell line, suggesting that the
      integrated microfluidic systems may be an unique approach for characterizing the
      cellular responses.

PMID- 19162425
TI  - Evaluation of surface and microstructure of differently plasticized chitosan
      films.
AB  - Surface and structural investigations of natural biopolymer (chitosan) films
      containing various conventionally applied hydrophilic plasticizers (glycerol and
      poly(ethylene glycol) 400) were performed and the results were compared, with the
      aim of acquiring new information concerning the formation of these plasticized
      films. The surface tests revealed that the water uptake, the water-binding
      properties (moisture content) and the polarity were higher for the film
      containing glycerol as plasticizer. Positronium lifetime measurements and NMR
      studies performed to evaluate the effects of the plasticizer on the polymer
      structure demonstrated relevant differences in the effects of the plasticizers.
      The influence of glycerol on the structure of the film formed was more intensive
      than that of PEG 400. It can be concluded that the surface properties of the
      films, which are very important for their storage and application, cannot be
      established exactly by means of structural tests. Both surface and structural
      tests must be performed before the formulation of this type of plasticized
      mucoadhesive films.

PMID- 19162426
TI  - Determination of azithromycin by ion-pair HPLC with UV detection.
AB  - An ion-pair reversed phase high performance liquid chromatographic method with UV
      detection was developed for the determination of azithromycin using sodium
      heptanesulfonate as an ion-pair reagent. The mobile phase consisted of a mixture
      of ammonium dihydrogen phosphate (0.045 M, pH 3.0 adjusted by phosphoric
      acid):acetonitrile 47:15 (v/v) and the concentration of sodium heptanesulfonate
      in the aqueous phase was 0.002 M. UV detection was performed at 210 nm. The
      chromatographic column was Dikma Technologies Diamonsil C18 column, 5 microm 150
      mm x 4.6 mm, which was maintained at 25 degrees C. Applying the method to a
      stability study of azithromycin eye drops, it was found that the related
      substance could be detected and the profile of the AZM peak was symmetrical and
      the column efficiency was high. Accordingly, it is suitable for the routine
      analysis and stability testing of azithromycin preparations.

PMID- 19162429
TI  - Low rates of loco-regional recurrence following extended lymph node dissection
      for gastric cancer.
AB  - AIM: The study by MacDonald et al. [Chemoradiotherapy after surgery compared with
      surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N
      Engl J Med 2001;345:725-30] has reported low loco-regional recurrence rates (19%)
      after gastric cancer resection and adjuvant radiotherapy. However, the lymph node
      dissection was often "inadequate". The aim of this retrospective study is to
      analyse if an extended lymph node dissection (D2) without adjuvant radiotherapy
      may achieve comparable loco-regional recurrence rates. METHODS: A prospective
      database of 200 patients who underwent a curative resection for gastric carcinoma
      from January 2000 to December 2006 was analysed. D2 lymph node dissection was
      standard. Recurrences were categorized as loco-regional, peritoneal, or distant.
      No patients received neoadjuvant or adjuvant radiotherapy. RESULTS: The in
      hospital mortality rate was 1% (2 patients). The mean number of dissected lymph
      nodes was 25.9. Overall and disease-free survival at 5years were 60.7% and 61.2%
      respectively. During the follow-up, 60 patients (30%) have recurred at 76 sites:
      38 (50%) distant metastases, 25 (32.9%) peritoneal metastases, and 13 (17.1%)
      loco-regional recurrences. The loco-regional recurrence was isolated in 6
      patients and associated with peritoneal or distant metastases in 7 patients. The
      mean time to the first recurrence was 18.9 (95% confidence interval: 15.0-21.9)
      months. CONCLUSIONS: Extended lymph node dissection is safe and warrants low loco
      regional recurrence rates.

PMID- 19162430
TI  - Adult active transportation: adding habit strength to the theory of planned
      behavior.
AB  - BACKGROUND: Many health behaviors have a history of repetition and, as a result,
      may become habitual. Because including a measure of habit strength may add depth
      to current theoretical models on health behavior, the present study explored the
      issue of habit strength within the context of the theory of planned behavior
      regarding adult bicycle use as a means of transportation. METHODS: Cross
      sectional data were gathered in a Dutch adult sample (n=317; mean age=42.09
      years; 46.7% men) in 2006 using self-administered questionnaires. Variables for
      the theory of planned behavior were assessed regarding bicycle use as a means of
      transportation; habit strength regarding bicycle use as a means of transportation
      was assessed with the validated Self-Reported Habit Index. Hierarchical
      regression analyses and interaction analyses using simple slope analyses were
      conducted. RESULTS: After controlling for variables for the theory of planned
      behavior, habit strength was the strongest predictor of bicycle use. In addition,
      simple slope analyses based on a significant interaction term, intention x habit,
      showed that intention was a significant predictor of bicycle use among those at
      low levels of habit strength for bicycle use (beta=0.67, p<0.001) but a weaker
      and nonsignificant predictor at high levels of habit strength (beta=0.10,
      p=0.136). CONCLUSIONS: Habit strength is a moderator of the intention-behavior
      relationship regarding bicycle use, with intention becoming less relevant when
      bicycle use increases in habit strength. Future determinant and intervention
      studies on physical activity may benefit from including a measure of habit
      strength--for instance, by identifying the differential effects of informational
      and environmental interventions.

PMID- 19162431
TI  - Walking and cycling to school: predictors of increases among children and
      adolescents.
AB  - BACKGROUND: Little is known about what happens to active commuting as children
      get older, and less is known about influences on changes in this behavior. This
      study examined predictors of increases in children's and adolescents' active
      commuting (walking or cycling) to/from school over a 2-year period. METHODS:
      Participants were initially recruited and assessed in 2001. Follow-up data were
      collected in 2004 and 2006 and analyzed in 2008. Participants were 121 children
      (aged 9.1+/-0.34 years in 2004) and 188 adolescents (aged 14.5+/-0.65 years in
      2004) from Melbourne, Australia. Parents and adolescents reported their
      perceptions of individual-level factors and of the neighborhood social and
      physical environment. Weekly active commuting (walking or cycling) to/from
      school, ranging from 0 to 10 trips/week was also proxy- or self-reported at the
      initial measurement and again 2 years later. Logistic regression analyses
      examined predictors of increases in active commuting over time. RESULTS: Children
      whose parents knew many people in their neighborhood were more likely to increase
      their active commuting (OR=2.6; CI=1.2, 5.9; p=0.02) compared with other
      children. Adolescents whose parents perceived there to be insufficient traffic
      lights and pedestrian crossings in their neighborhood were less likely to
      increase their active commuting over 2 years (OR=0.4; CI=0.2, 0.8; p=0.01),
      whereas adolescents of parents who were satisfied with the number of pedestrian
      crossings were more likely to increase their active commuting (OR=2.4; CI=1.1,
      5.4; p=0.03) compared with other adolescents. CONCLUSIONS: Social factors and
      physical environmental characteristics were the most important predictors of
      active commuting in children and adolescents, respectively.

PMID- 19162432
TI  - Adolescent vaccination: recommendations from the National Vaccine Advisory
      Committee.

PMID- 19162433
TI  - Perceived accessibility of cigarettes among youth: a prospective cohort study.
AB  - BACKGROUND: The accessibility of tobacco for youth is difficult to measure,
      partly because of the varied sources of cigarettes. Perceptions about the
      accessibility of cigarettes assesses availability from all potential sources and
      has been found to predict future smoking. This study examines the determinants of
      perceived accessibility from the perspective of a longitudinal study. METHODS:
      Data were derived from the second Development and Assessment of Nicotine
      Dependence in Youth study, a 4-year longitudinal study of 1246 sixth-grade
      students who underwent up to 11 in-person interviews from 2002 to 2006. Perceived
      accessibility was assessed prospectively by asking students whether they agreed
      or disagreed with the statement It would be easy for me to get a cigarette.
      RESULTS: At baseline, the average age was 12 years; 85% had never before smoked;
      more than 21% perceived that cigarettes were easy to obtain. Perceived
      accessibility increased over the 4 years among the cohort. Youth with friends who
      smoked or whose parents allowed the watching of R-rated movies were more likely
      to perceive easy accessibility of cigarettes. Among nonsmokers, there was a dose
      response relationship between perceived accessibility and exposure to smoking in
      the family environment. Nonsmokers who knew commercial sources of cigarettes also
      had higher perceived accessibility. CONCLUSIONS: Several potentially preventable
      exposures to tobacco in the family and social environment contribute to
      confidence among some youth that cigarettes are easy to obtain. Further studies
      are needed to determine if modifying these factors (e.g., through programs to
      reduce the exposure of youth to tobacco products in the home) might reduce
      perceived accessibility.

PMID- 19162434
TI  - Viral RNA testing in hepatitis C antibody-positive veterans.
AB  - BACKGROUND: Chronic hepatitis C virus (HCV) infection affects approximately 1.3%
      of the U.S. population. As up to 30% of HCV-antibody (anti-HCV)-positive patients
      have negative HCV ribonucleic acid (RNA), indicating resolution of infection, VA
      (Veterans Affairs) guidelines recommend RNA testing on all anti-HCV-positive
      patients. As HCV RNA testing is a prequel to treatment, perceived eligibility for
      treatment may influence the decision to order an RNA test. This study was
      designed to determine the patient and healthcare facility factors associated with
      patient receipt of HCV RNA testing. METHODS: Two logistic regression analyses
      were conducted in anti-HCV-positive patients, including the entire sample and
      then on a subsample excluding sites with routine HCV RNA testing policies, using
      data stored in the VA Southern California Network data warehouse. Significant
      patient- and site-level predictors of patient receipt of HCV RNA testing were
      determined. RESULTS: Of the 13,257 antibody-positive patients, 76% received HCV
      RNA testing. Excluding sites with routine HCV RNA testing, patients aged >65
      years (RR=0.79) and illicit drug users (RR=0.94) were significantly less likely
      to receive HCV RNA testing. Patients with abnormal transaminases (RR=1.14),
      presence of non-HCV hepatitis (RR=1.08), or decompensated liver disease (RR=1.22)
      were significantly more likely to receive HCV RNA testing. CONCLUSIONS: Without
      policies for routine RNA testing, patients with hepatitic C who either are aged
      >65 years or are illicit drug users are less likely to be tested. Also, patient
      receipt of RNA testing becomes dependent on clinical cues of hepatic
      decompensation or inflammation. The results support the implementation of routine
      RNA testing for anti-HCV-positive patients.

PMID- 19162435
TI  - [Depression in Parkinson's disease].

PMID- 19162437
TI  - Imagery and fear influence height perception.
AB  - The current study tested whether height overestimation is related to height fear
      and influenced by images of falling. To assess perceptual biases, participants
      high (n=65) versus low (n=64) in height fear estimated the vertical extents of
      two balconies using a visual matching task. On one of the balconies, participants
      engaged in an imagery exercise designed to enhance the subjective sense that they
      were acting in a dangerous environment by picturing themselves falling. As
      expected, we found that individuals overestimated the balcony's height more after
      they imagined themselves falling, particularly if they were already afraid of
      heights. These findings suggest that height fear may serve as a vulnerability
      factor that leads to perceptual biases when triggered by a stressor (in this
      case, images of falling).

PMID- 19162436
TI  - Variant in RGS2 moderates posttraumatic stress symptoms following potentially
      traumatic event exposure.
AB  - Polymorphisms in the RGS2 (regulator of G-protein signaling 2) gene were found to
      be associated with anxious behavior in mice and anxiety in humans. We examined
      whether rs4606, a single nucleotide polymorphism (SNP) of RGS2, and social
      support moderated risk for PTSD in an epidemiologic sample. The study examines
      607 adults from the 2004 Florida Hurricanes study who returned buccal DNA samples
      via mail. rs4606 was associated with increased symptoms of posthurricane PTSD
      symptoms under conditions of high hurricane exposure and low social support
      (P<.05). Further, this polymorphism was associated with lifetime PTSD symptoms
      under conditions of lifetime exposure to a potentially traumatic event, and low
      social support (P<.001). These gene by environment interactions remained
      significant after adjustment for sex, ancestry, and age. RGS2 rs4606 modifies
      risk of postdisaster and lifetime PTSD symptoms under conditions of high stressor
      exposure. This is the first demonstration of gene-environment interaction for
      this locus.

PMID- 19162438
TI  - Leiomyosarcoma of the iliac vein.
AB  - Leiomyosarcoma of the iliac vein is a very uncommon tumor. We report the case of
      a 55-year-old man with leiomyosarcoma of the left iliac vein. The patient had
      abdominal pain and hematuria. Abdominal ultrasound and computed tomography
      scanning demonstrated a well-defined mass in the left inguinal region, probably
      arising from the left iliac vein. Ultrasound-guided needle-core biopsy was
      consistent with a malignant growth. The patient was operated on, and a neoplastic
      multinodular mass attached to the posterolateral wall of the iliac vein was
      found. The tumor was resected en bloc, and venous reconstruction was undertaken
      using a saphenous vein segment. The postoperative course was uneventful, and the
      histologic study of the resected specimen was confirmed microscopically to be a
      leiomyosarcoma. No signs of recurrence or metastasis were present 29 months after
      complete surgical resection.

PMID- 19162439
TI  - Encopresis, soiling and constipation in children and adults with developmental
      disability.
AB  - Children and adults with developmental disabilities are more likely to evince
      encopresis, soiling and constipation than the general population. This set of
      related behaviors can produce a great deal of stress and can be a major
      restriction in independent living. This paper provides a review of the current
      state of knowledge on the prevalence, etiology, assessment and treatment of this
      co-occurring set of disorders. These problems are more common in persons with
      developmental disabilities then the general population. Furthermore, classical
      and operant treatment methods appear to be the best supported interventions for
      most cases. Strengths and weaknesses of the current research base are discussed
      along with potential avenues for future research.

PMID- 19162440
TI  - An international survey indicated that unpublished systematic reviews exist.
AB  - OBJECTIVE: To determine the frequency of unpublished systematic reviews (SRs) and
      explore factors contributing to their occurrence. STUDY DESIGN AND SETTING: First
      or corresponding authors from a sample of SRs published in 2005 were asked to
      participate in a 26-item survey administered through the Internet, facsimile, and
      postal mail. Outcomes included median and range of published and unpublished SRs,
      and barriers, facilitators, and reasons for not publishing SRs. Descriptive
      analyses were performed. RESULTS: 55.7% (348 of 625) of those invited
      participated, half of which were from Europe and 22.7% were from the United
      States. Participants reported 1,405 published (median: 2.0, range: 1-150) and 199
      unpublished (median: 2.0, range: 1-33) SRs. Lack of time and lack of funding and
      organizational support were barriers, whereas time availability and self
      motivation were facilitators to publishing reviews. For most recent unpublished
      SRs (n=52), the reasons for not publishing included lack of time (12 of 52,
      23.0%), the manuscript being rejected (10 of 52, 19.0%), and operational issues
      (six of 52, 11.5%). CONCLUSION: Unpublished SRs do exist. Lack of time, funding,
      and organizational support were consistent reasons for not publishing SRs.
      Statistical significance of SR results was not reported as being a major barrier
      or reason for not publishing. Further research on unpublished SRs is warranted.

PMID- 19162441
TI  - CD103 is dispensable for anti-viral immunity and autoimmunity in a mouse model of
      virally-induced autoimmune diabetes.
AB  - Recent studies suggest a beneficial role for blocking CD103 signaling in
      preventing islet allograft rejection and thus Type 1 diabetes (T1D) in non-obese
      diabetic (NOD) mice. However, antibody blockade approaches generally raise anti
      microbial safety issues, necessitating additional studies to address the possible
      adverse effects of antibody therapy. Here we report that CD103 had no significant
      impact on the development of primary and memory CD8(+) or CD4(+) responses after
      acute lymphocytic choriomeningitis virus (LCMV) infection. In addition, CD103 was
      found to be dispensable for T1D progression in a rapid, CD8-mediated virally
      induced T1D model (the rat insulin promoter [RIP]-LCMV), suggesting that its
      previous efficacy in the NOD mouse model may not be related to its effect on the
      generation, memory conversion and/or effector function of CD8(+) or CD4(+) T
      cells. While the data does not preclude a role for CD103 in T1D in its entirety,
      the current study does provide much evidence to suggest that CD103 blockade may
      prove to be a safe intervention for autoimmunity and allo-transplantation. While
      in cases of rapid microbial (CD8)-driven T1D CD103 antibody blockade may not
      limit disease progression or severity, in mucosally-driven cases of T1D anti
      CD103 antibody treatment may provide a new and safe therapeutic avenue.

PMID- 19162442
TI  - Segmental Le Fort I osteotomy with bone grafting in unilateral severely atrophied
      maxilla.
AB  - This study describes the use of a segmental Le Fort I osteotomy for
      interpositional autogenous iliac bone grafts in 5 patients with severe unilateral
      atrophy of the maxilla. Unilateral pterygomaxillary disjunction and osteotomy of
      the lateral and medial walls of the maxillary sinus were performed. The mucosa of
      the maxillary sinus was preserved and lifted cranially. It was stabilized with
      autogenous cancellous bone grafts. One side of the maxilla was gently
      downfractured until it replaced the original morphology of the alveolar crest.
      The inter-arch space was therefore reduced to the ideal level for placing
      implants. Lateral widening of the alveolar crest was obtained with on-lay bone
      grafts. Segmental osteotomy with bone grafting is a modification of Le Fort I
      swing osteotomy that has several advantages. The in-lay graft was not resorbed
      because it was rapidly revascularized and implant placement was delayed. This
      article presents a surgical technique for the reduction of vertical inter-arch
      space for the correct positioning of osseointegrated implants.

PMID- 19162443
TI  - Competence to consent and insight in schizophrenia: is there an association? A
      pilot study.
AB  - OBJECTIVE: The capacity to consent to treatment or research of patients with
      severe mental disorders is the focus of important ethical and clinical debate.
      Many studies evaluate the links between clinical symptoms and the capacity to
      consent. The aim of this study was to explore the correlations existing between
      the competence to consent to treatment and the level of awareness of the disease
      (insight) in patients suffering from schizophrenia in a cross-sectional study.
      METHOD: Participants included 60 outpatients meeting the criteria for a DSM-IV
      diagnosis of schizophrenia. Measures included the MacArthur Competence Assessment
      tool for Treatment (MacCAT-T), the Scale to Assess Unawareness of Mental Disorder
      (SUMD) and psychopathology rating scales including the Positive and Negative
      Syndrome Scale (PANSS). RESULTS: The MacCAT-T dimension "Understanding" was found
      to be negatively correlated with negative and total PANSS scores but was not
      found to be correlated with any of the SUMD dimensions. However a systematic
      negative correlation was observed between the MacCAT-T "Appreciation" and
      "Reasoning" dimensions and the five SUMD dimensions. Finally, the MacCAT-T
      "Expressing a choice" dimension was found to be negatively correlated with two
      SUMD dimensions: "Having a mental disorder" and "consequences of the mental
      disorder". CONCLUSIONS: These findings suggest an important correlation between
      the competence to consent to treatment and insight, a clinical variable currently
      assessed by clinicians. We hypothesized that this link could be mediated by
      cognitive impairments in schizophrenia. Emphasis should be placed on developing
      prospective studies comparing the courses of insight, cognitive disorders and
      capacity to consent in schizophrenia.

PMID- 19162444
TI  - Predictors of starting to smoke cigarettes in patients with first episode
      psychosis.
AB  - INTRODUCTION: Cigarette smoking is common in psychotic disorders and may be
      initiated in an attempt to control features of illness. However, genetic,
      obstetric and early life conditions are risks for starting to smoke in the
      general population but their role in psychotic patients is unclear. METHOD:
      Smoking history and the putative predictors of starting to smoke were assessed in
      a community-wide sample of 115 first episode psychosis patients. The proportion
      that initiated smoking was compared with that from population surveys and the
      impact of risk factors was assessed within the patient sample. RESULTS: Most
      patients began smoking before illness onset and the proportion who initiated
      smoking was significantly high by the onset of a functional decline. Gestational
      tobacco exposure was a risk for smoking and was also associated with low
      birthweight, poor academic achievement, and obesity. Low familial socioeconomic
      position but not familial psychiatric problems also predicted smoking initiation.
      DISCUSSION: In most cases, smoking preceded illness onset and was not a response
      to early features of illness. General population predictors of starting to smoke
      were also associated with smoking initiation in psychotic patients. Of these
      risks, exposure to tobacco during gestation is noteworthy in that it affects
      brain development and is associated with cognitive, behavioral, psychiatric and
      general health problems. In addition, nicotine interacts with other substances of
      abuse. The initiation of smoking before illness onset and the association with
      developmental problems raises the question of whether cigarette smoking
      influences some aspects of illness in patients with psychosis.

PMID- 19162445
TI  - Increased pituitary volume in schizophrenia spectrum disorders.
AB  - While hypothalamic-pituitary-adrenal (HPA) axis hyperactivity has been implicated
      in psychotic disorders, previous magnetic resonance imaging (MRI) studies of the
      pituitary gland volume in schizophrenia have yielded controversial results. It is
      also unknown whether patients with schizophrenia spectrum such as schizotypal
      disorder exhibit pituitary volume changes. In this study, we investigated the
      pituitary volume using MRI in 47 schizotypal disorder patients (29 males, mean
      age=25.0 years), 72 schizophrenia patients (38 males, mean age=26.2 years), and
      81 age and gender matched healthy controls (46 males, mean age=24.5 years). Both
      patient groups had a larger pituitary volume compared with controls, but no
      difference was found between the schizophrenia and schizotypal patients. The
      pituitary volume was larger in females than in males for all diagnostic groups.
      There was no association between the pituitary volume and type (typical versus
      atypical), daily dosage, or duration of antipsychotic medication in either
      patient group. These findings are consistent with a stress-diathesis model of
      schizophrenia and further suggest that the schizotypal patients share HPA axis
      hyperactivity with young established schizophrenia patients reflecting a common
      vulnerability to stress within the schizophrenia spectrum.

PMID- 19162446
TI  - Linkage analysis of three genetic loci for disease susceptibility in Tunisian
      Psoriatic families.

PMID- 19162447
TI  - Altered expression of fatty acid desaturases in the skin of dogs with atopic
      dermatitis.

PMID- 19162448
TI  - Differentiation of Trichophyton rubrum clinical isolates from Japanese and
      Chinese patients by randomly amplified polymorphic DNA and DNA sequence analysis
      of the non-transcribed spacer region of the rRNA gene.
AB  - BACKGROUND: Trichophyton rubrum is the most common pathogen causing
      dermatophytosis worldwide. Recent genetic investigations showed that the
      microorganism originated in Africa and then spread to Europe and North America
      via Asia. OBJECTS: We investigated the intraspecific diversity of T. rubrum
      isolated from two closely located Asian countries, Japan and China. METHODS: A
      total of 150 clinical isolates of T. rubrum obtained from Japanese and Chinese
      patients were analyzed by randomly amplified polymorphic DNA (RAPD) and DNA
      sequence analysis of the non-transcribed spacer (NTS) region in the rRNA gene.
      RESULTS: RAPD analysis divided the 150 strains into two major clusters, A and B.
      Of the Japanese isolates, 30% belonged to cluster A and 70% belonged to cluster
      B, whereas 91% of the Chinese isolates were in cluster A. The NTS region of the
      rRNA gene was divided into four major groups (I-IV) based on DNA sequencing. The
      majority of Japanese isolates were type IV (51%), and the majority of Chinese
      isolates were type III (75%). CONCLUSIONS: These results suggest that although
      Japan and China are neighboring countries, the origins of T. rubrum isolates from
      these countries may not be identical. These findings provide information useful
      for tracing the global transmission routes of T. rubrum.

PMID- 19162449
TI  - Tigecycline in combination with other antimicrobials: a review of in vitro,
      animal and case report studies.
AB  - Tigecycline has been investigated in combination with other antibacterials
      against a wide range of susceptible and multiresistant Gram-positive and Gram
      negative bacteria. Combinations have been analysed in vitro, in animal models and
      in human case reports. In vitro, tigecycline combined with other antimicrobials
      produces primarily an indifferent response (neither synergy nor antagonism).
      Nevertheless, synergy occurred when tigecycline was combined with rifampicin
      against 64-100% of Enterococcus spp., Streptococcus pneumoniae, Enterobacter spp.
      and Brucella melitensis isolates. Combinations of tigecycline with amikacin also
      showed synergy for 40-100% of Enterobacter spp., Klebsiella pneumoniae, Proteus
      spp. and Stenotrophomonas maltophilia isolates. Moreover, bactericidal synergisms
      occurred with tigecycline plus amikacin against problematic Acinetobacter
      baumannii and Proteus vulgaris, and with colistin against K. pneumoniae. Data
      from animal experiments and case reports, although limited, displayed consistent
      beneficial activity of tigecycline in combination with other antibacterials
      against multiresistant organisms, including vancomycin against penicillin
      resistant S. pneumoniae in experimental meningitis, gentamicin against
      Pseudomonas aeruginosa in experimental pneumonia, daptomycin against Enterococcus
      faecium endocarditis, and colistin against K. pneumoniae bacteraemia and P.
      aeruginosa osteomyelitis. Antagonism was extremely rare in vitro and was not
      reported in vivo. Thus, tigecycline may be combined with a second antimicrobial
      as part of a combination regimen.

PMID- 19162450
TI  - In vitro activity of caspofungin and voriconazole against uncommon Candida spp.

PMID- 19162451
TI  - A multitechnique study of preferential protein adsorption on hydrophobic and
      hydrophilic plasma-modified polymer surfaces.
AB  - The adsorption process of albumin, lysozyme and lactoferrin was investigated onto
      polymer surfaces, both hydrophobic and hydrophilic treated by oxygen-plasma. In
      particular thin films of polyhydroxymethylsiloxane (about 90 degrees of static
      water contact angle) were converted by oxygen plasma treatments at reduced
      pressure into hydrophilic SiO(x) phases (less than 10 degrees of water contact
      angle). The protein adsorption process was investigated in situ by quartz crystal
      microbalance with dissipation monitoring in terms of coverage and kinetics
      mechanism, while chemical structure and topography of the protein adlayers were
      studied ex situ by angular-resolved XPS and atomic force microscopy,
      respectively. The plasma surface modification of the polymer film drastically
      modified the adsorption process of the three proteins, both in terms of kinetics
      and coverage.

PMID- 19162452
TI  - Control over micro-fluidity of liposomal membranes by hybridizing metal
      nanoparticles.
AB  - This study introduces a facile method to hybridize metal nanoparticles with lipid
      vesicles, which allows us to control over their membrane micro-fluidity. We have
      fabricated these hybrid liposomes by directly hybridizing metal nanoparticles
      with lipid bilayers solely consisting of 1,2-dipalmitoyl-sn-glycero-3
      phosphatidylcholine (DPPC). For this, we have used the dehydration and
      rehydration method. Characterizing their morphology and micro-fluidity, in which
      we have used electron microscopy and fluorescence anisotropy spectroscopy,
      enables us to demonstrate that metal nanoparticles with different surface
      properties create interactions with either phosphorus end groups or hydrophobic
      tails of DPPC, thereby resulting in decrease in micro-fluidity of the assembled
      lipid membranes, especially for the hydrophobic layers. Our approach to hybridize
      metal nanoparticles in between lipid layers offers a flexible means that allows
      us to obtain a liposome system with more controllable membrane properties.

PMID- 19162453
TI  - Polyelectrolyte microcapsule interactions with cells in two- and three
      dimensional culture.
AB  - Microcapsules fabricated by layer-by-layer self-assembly have unique
      physicochemical properties that make them attractive for drug delivery
      applications. This study chiefly investigated the biocompatibility of one of the
      most stable types of microcapsules, those composed of poly-(sodium 4-styrene
      sulfonate) [PSS] and poly-(allylamine hydrochloride) [PAH], with cells cultured
      on two-dimensional (2D) substrates and in three-dimensional (3D) matrices. C6
      glioma and 3T3 fibroblast cell morphology was observed after 24h of co-culture
      with PSS/PAH microcapsules on a 2D substrate. Cells were also cultured with four
      other types of microcapsules, each composed of at least one naturally occurring
      polyelectrolyte. At microcapsule to cell ratios up to 100:1, it was found that
      PSS/PAH microcapsules do not affect number of viable cells more substantially
      than do the other microcapsules investigated. However, differences in number of
      viable cells were found as a function of microcapsule composition, and our
      results suggest particular biochemical interactions between cells and
      internalized microcapsules, rather than mechanical effects, are responsible for
      these differences. We then investigated the effects of PSS/PAH microcapsules on
      cells embedded in 3D collagen matrices, which more closely approximate the tumor
      environments in which microcapsules may be useful drug delivery agents. Matrix
      structure, cell invasion, and volumetric spheroid growth were investigated, and
      we show that these microcapsules have a negligible effect on cell invasion and
      tumor spheroid growth even at high concentration. Taken together, this work
      suggests that PSS/PAH microcapsules have sufficiently high biocompatibility with
      at least some cell lines for use as proof of principle drug delivery agents in in
      vitro studies.

PMID- 19162454
TI  - Studies on preventive effects of diphenyl diselenide on acetaminophen-induced
      hepatotoxicity in rats.
AB  - Organoselenium are compounds with important antioxidant activity and with many
      biological activities interesting from pharmacological point of view. The aim of
      this study was to evaluate the protective effect of diphenyl diselenide (PhSe)2
      on hepatotoxicity caused by administration of acetaminophen (AA) in rats. Rats
      received (PhSe)2 orally (31mg/kg, dissolved in canola oil) for 2 days. After the
      second day of treatment, rats received AA orally (2g/kg) in unique dose. Twenty
      four hours after the last administration of AA, plasma was used for biochemical
      assays aspartate (AST) and alanine aminotransferases (ALT), alkaline phosphatase
      (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (gamma-GT)
      activities. Glutathione-S-transferase (GST), delta-aminolevulinic dehydratase
      (delta-ALA-D) and catalase activities as well as ascorbic acid and TBARS levels
      were determined in the liver of rats. (PhSe)2 protected against the increase in
      AST, ALT, ALP, LDH and gamma-GT activities induced by AA exposure to rats. The
      histological data showed that sections of liver from AA-exposed rats presented
      intense cellular necrosis, characterized by the presence of Kupffer cells and
      other infiltrating cells, mainly around of the centrilobular vein. (PhSe)2
      significantly attenuated AA-induced hepatic histopathological alterations.
      Administration of (PhSe)2 protected against the increase in TBARS levels and the
      decrease in delta-ALA-D and GST activities as well as ascorbic acid content
      induced by AA exposure in rats. Catalase activity remained unaltered in all
      treated groups. The protective effect of (PhSe)2 against hepatotoxicity caused by
      AA exposure in rats was demonstrated.

PMID- 19162455
TI  - Prediction of periventricular leukomalacia. Part I: Selection of hemodynamic
      features using logistic regression and decision tree algorithms.
AB  - OBJECTIVE: Periventricular leukomalacia (PVL) is part of a spectrum of cerebral
      white matter injury which is associated with adverse neurodevelopmental outcome
      in preterm infants. While PVL is common in neonates with cardiac disease, both
      before and after surgery, it is less common in older infants with cardiac
      disease. Pre-, intra-, and postoperative risk factors for the occurrence of PVL
      are poorly understood. The main objective of the present work is to identify
      potential hemodynamic risk factors for PVL occurrence in neonates with complex
      heart disease using logistic regression analysis and decision tree algorithms.
      METHODS: The postoperative hemodynamic and arterial blood gas data (monitoring
      variables) collected in the cardiac intensive care unit of Children's Hospital of
      Philadelphia were used for predicting the occurrence of PVL. Three categories of
      datasets for 103 infants and neonates were used-(1) original data without any
      preprocessing, (2) partial data keeping the admission, the maximum and the
      minimum values of the monitoring variables, and (3) extracted dataset of
      statistical features. The datasets were used as inputs for forward stepwise
      logistic regression to select the most significant variables as predictors. The
      selected features were then used as inputs to the decision tree induction
      algorithm for generating easily interpretable rules for prediction of PVL.
      RESULTS: Three sets of data were analyzed in SPSS for identifying statistically
      significant predictors (p<0.05) of PVL through stepwise logistic regression and
      their correlations. The classification success of the Case 3 dataset of extracted
      statistical features was best with sensitivity (SN), specificity (SP) and
      accuracy (AC) of 87, 88 and 87%, respectively. The identified features, when used
      with decision tree algorithms, gave SN, SP and AC of 90, 97 and 94% in training
      and 73, 58 and 65% in test. The identified variables in Case 3 dataset mainly
      included blood pressure, both systolic and diastolic, partial pressures pO(2) and
      pCO(2), and their statistical features like average, variance, skewness (a
      measure of asymmetry) and kurtosis (a measure of abrupt changes). Rules for
      prediction of PVL were generated automatically through the decision tree
      algorithms. CONCLUSIONS: The proposed approach combines the advantages of
      statistical approach (regression analysis) and data mining techniques (decision
      tree) for generation of easily interpretable rules for PVL prediction. The
      present work extends an earlier research [Galli KK, Zimmerman RA, Jarvik GP,
      Wernovsky G, Kuijpers M, Clancy RR, et al. Periventricular leukomalacia is common
      after cardiac surgery. J Thorac Cardiovasc Surg 2004;127:692-704] in the form of
      expanding the feature set, identifying additional prognostic factors (namely
      pCO(2)) emphasizing the temporal variations in addition to upper or lower values,
      and generating decision rules. The Case 3 dataset was further investigated in
      Part II for feature selection through computational intelligence.

PMID- 19162456
TI  - Prediction of periventricular leukomalacia. Part II: Selection of hemodynamic
      features using computational intelligence.
AB  - OBJECTIVE: The objective of Part II is to analyze the dataset of extracted
      hemodynamic features (Case 3 of Part I) through computational intelligence (CI)
      techniques for identification of potential prognostic factors for periventricular
      leukomalacia (PVL) occurrence in neonates with congenital heart disease. METHODS:
      The extracted features (Case 3 dataset of Part I) were used as inputs to CI based
      classifiers, namely, multi-layer perceptron (MLP) and probabilistic neural
      network (PNN) in combination with genetic algorithms (GA) for selection of the
      most suitable features predicting the occurrence of PVL. The selected features
      were next used as inputs to a decision tree (DT) algorithm for generating easily
      interpretable rules of PVL prediction. RESULTS: Prediction performance for two CI
      based classifiers, MLP and PNN coupled with GA are presented for different number
      of selected features. The best prediction performances were achieved with 6 and 7
      selected features. The prediction success was 100% in training and the best
      ranges of sensitivity (SN), specificity (SP) and accuracy (AC) in test were 60
      73%, 74-84% and 71-74%, respectively. The identified features when used with the
      DT algorithm gave best SN, SP and AC in the ranges of 87-90% in training and 80
      87%, 74-79% and 79-82% in test. Among the variables selected in CI, systolic and
      diastolic blood pressures, and pCO(2) figured prominently similar to Part I.
      Decision tree based rules for prediction of PVL occurrence were obtained using
      the CI selected features. CONCLUSIONS: The proposed approach combines the
      generalization capability of CI based feature selection approach and generation
      of easily interpretable classification rules of the decision tree. The
      combination of CI techniques with DT gave substantially better test prediction
      performance than using CI and DT separately.

PMID- 19162457
TI  - The implementation of an advanced treatment planning algorithm in the treatment
      of lung cancer with conventional radiotherapy.
AB  - AIMS: Recent improvements in planning systems have made use of sophisticated dose
      calculation algorithms such as collapsed cone, a realistic possibility for
      routine lung radiotherapy treatment planning. However, it is more difficult to
      achieve ICRU 50/62 compliant plans (i.e. a minimum of 95% of the prescribed dose
      to the planning target volume) with the collapsed cone algorithm, due to the more
      accurate modelling of dose in heterogeneous media. The aim of this study was to
      determine planning guidance for the implementation of the collapsed cone
      algorithm for conventional radiotherapy treatment planning. MATERIALS AND
      METHODS: Ten pencil beam lung plans were recalculated using the collapsed cone
      algorithm. Then, beam weights were optimised on the recalculated collapsed cone
      plan, without altering field sizes. Finally, both field sizes and beam weights
      were optimised on the same plan in an attempt to deliver a minimum of either 90
      or 95% of the prescribed dose to the planning target volume. Thus, four sets of
      plans were available for comparison. RESULTS: Compared with pencil beam plans
      recalculated with the collapsed cone algorithm, all collapsed cone plans had
      improved dose coverage of the planning target volume. For two of the beam weight
      optimised plans, less than 80% of the planning target volume received 90% of the
      prescribed dose. For the field size, beam weight optimised plans, nearly 100% of
      the planning target volume attained 90% of the prescribed dose, with the clinical
      target volume generally reaching 95%. Compared with the original pencil beam
      plans, the volume of lung receiving greater than 20 Gy (V(20)) increased by 3.1
      and 6.8%, respectively, for those plans optimised to deliver a minimum of 90 or
      95% of the prescribed dose to the planning target volume. CONCLUSIONS: We suggest
      that the collapsed cone algorithm might reasonably be implemented for
      conventional radiotherapy treatment planning with the aim of delivering a minimum
      of 90% of the prescribed dose to the planning target volume and 95% of the
      prescribed dose to the clinical target volume. This guidance offers consistent
      prescription of dose to target volumes.

PMID- 19162458
TI  - Capitalising upon political opportunities to reform drug policy: a case study
      into the development of the Australian "Tough on Drugs-Illicit Drug Diversion
      Initiative".
AB  - BACKGROUND: The introduction of political "war on drug" strategies and Prime
      Ministerial advisory groups increase opportunities for drug policy reform. Yet
      the strengths and limitations of capitalising upon political opportunities remain
      unclear. This paper provides a unique insight into the development of an
      Australian reform, the "Tough on Drugs-Illicit Drug Diversion Initiative." This
      reform was one of the major policies to emerge out of the Federal Coalition
      "Tough on Drugs" strategy. In spite of the rhetoric the Illicit Drug Diversion
      Initiative (IDDI) has diverted minor drug users away from the traditional
      criminal justice system. METHODS: This paper draws upon interviews with 16 expert
      policy makers involved in the advocacy and negotiations leading up to the
      adoption of the IDDI to examine what drove the reform and how and why a pragmatic
      reform emerged. RESULTS: The IDDI culminated from the presence of five main
      drivers: a crisis in relation to heroin and crime, antagonism towards the
      government, a weak but growing evidence-base on the merits of drug diversion, a
      shift in law enforcement attitudes and persuasive advocacy by a group of non
      government experts. This paper contends that the Prime Minister's new "Tough on
      Drugs" strategy and expanded governance arrangements created new space for policy
      actors to intervene in the policy formulation process and to convert the
      governments proposed "zero tolerance" response into a more humane and potentially
      effective response. CONCLUSION: This paper concludes that contrary to popular
      opinion political venues and politicisation may offer valuable opportunities for
      drug policy reform. The challenge for researchers and policy advocates is to see
      how they can best utilise political venues to obtain pragmatic reform.

PMID- 19162459
TI  - Improvement of permeability of waste sludge by mixing with slag or construction
      and demolition waste.
AB  - To determine the allowable ratio of waste sludge required to ensure an aerobic
      zone in the landfill, we investigated sludge permeability, which involved mixing
      sludge, the major landfill waste in Japan, at different mixing ratios with other
      wastes (slag and construction and demolition waste (C&D)). We measured parameters
      of sample permeability and analyzed parameters that exert a large influence on
      oxygen penetration depth with a simulation model accounting for both diffusion
      and convection driven by temperature gradients. We also determined the critical
      volumetric contents in which gas and/or water permeability change significantly
      when sludge is mixed with sand or gravel. From the results of the simulations,
      gas permeability of the layer, the difference between inside and outside
      temperatures and the oxygen consumption rate exert a large influence on the
      resulting oxygen penetration depth. The allowable ratio of sludge required to
      ensure an aerobic zone in the landfill was determined by considering the balance
      of the above three parameters. By keeping volumetric sludge content to below 25%,
      air convection and oxygen penetration depth of several meters were achieved in
      the modeling.

PMID- 19162460
TI  - Real-time PCR microfluidic devices with concurrent electrochemical detection.
AB  - Electrochemistry-based detection methods hold great potential towards development
      of hand-held nucleic-acid analyses instruments. In this work, we demonstrate the
      implementation of in situ electrochemical (EC) detection method in a microfluidic
      flow-through EC-qPCR (FTEC-qPCR) device, where both the amplification of the
      target nucleic-acid sequence and subsequent EC detection of the PCR amplicon are
      realized simultaneously at selected PCR cycles in the same device. The FTEC-qPCR
      device utilizes methylene blue (MB), an electroactive DNA intercalator, for
      electrochemical signal measurements in the presence of PCR reagent components.
      Our EC detection method is advantageous, when compared to other existing EC
      methods for PCR amplicon analysis, since FTEC-qPCR does not require probe
      modified electrodes, or asymmetric PCR, or solid-phase PCR. Key technical issues
      related to surface passivation, electrochemical measurement, PCR inhibition by
      metal electrode, bubble-free PCR, were investigated. By controlling the
      concentration of MB and the exposure of PCR mixture to the bare metal electrode,
      we successfully demonstrated electrochemical measurement of MB in solution-phase,
      symmetric PCR by amplifying a fragment of lambda phage DNA. The threshold cycle
      (C(t)) values for both the electrochemical and fluorescence-based assays
      decreased linearly with the increase of the input target quantity. The
      sensitivity of EC-based detection of PCR products is comparable to the
      sensitivity of an optical fluorescence detection system.

PMID- 19162461
TI  - Carbon nanotube array: a new MIP platform.
AB  - Here we demonstrate that a free-standing carbon nanotube (CNT) array can be used
      as a large surface area and high porosity 3D platform for molecular imprinted
      polymer (MIP), especially for surface imprinting. The thickness of polymer
      grafted around each CNT can be fine-tuned to imprint different sizes of target
      molecules, and yet it can be thin enough to expose every imprint site to the
      target molecules in solution without sacrificing the capacity of binding sites.
      The performance of this new CNT-MIP architecture was first assessed with a
      caffeine-imprinted polypyrrole (PPy) coating on two types of CNT arrays: sparse
      and dense CNTs. Real-time pulsed amperometric detection was used to study the
      rebinding of the caffeine molecules onto these CNT-MIPPy sensors. The dense CNT
      MIPPy sensor presented the highest sensitivity, about 15 times better when
      compared to the conventional thin film, whereas an improvement of 3.6 times was
      recorded on the sparse CNT. However, due to the small tube-to-tube spacing in the
      dense CNT array, electrode fouling was observed during the detection of
      concentrated caffeine in phosphate buffer solution. A new I-V characterization
      method using pulsed amperometry was introduced to investigate the electrical
      characterization of these new devices. The resistance value derived from the I-V
      plot provides insight into the electrical conductivity of the CNT transducer and
      also the effective surface area for caffeine imprinting.

PMID- 19162462
TI  - The development of a MIP-optosensor for the detection of monoamine naphthalenes
      in drinking water.
AB  - To enhance the advantages of fluorescent flow-through sensing for drinking water
      we have designed a novel sensing matrix based on molecularly imprinted polymers
      (MIPs). The synergic combination of a tailor-made MIP recognition with a
      selective room temperature fluorescence detection is a novel concept for
      optosensing devices and is assessed here for the simple and selective
      determination of pollutants in water. We describe a simple approach to preparing
      synthetic receptors for monoamine naphthalene compounds (MA-NCs) using non
      covalent molecular imprinting techniques and naphthalene as template. We examine
      in detail the binding characteristics of the imprinted polymer and describe the
      flow-through sensor of MA-NCs by solid-surface fluorescence. Its detection limits
      for recognizing 1-naphthylamine (1-NA) and 2-naphthylamine (2-NA) separately are
      26 ngmL(-1) and 50 ngmL(-1), respectively, and it also determines 1-NA and 2-NA
      simultaneously with a detection limit of 45 ngmL(-1). All the instrumental,
      chemical and flow variables were carefully optimized and an interference study
      was carried out to demonstrate its applicability and selectivity. Finally, we
      applied it to the analysis of 1-NA and 2-NA in tap and mineral waters, obtaining
      a 98% average recovery rate.

PMID- 19162463
TI  - Passaged neural stem cell-derived neuronal networks for a portable biosensor.
AB  - We have previously demonstrated a portable biosensor that utilizes networks of
      mammalian neurons on microelectrode arrays (MEAs) as the sensing element. These
      neuronal cultures on MEAs are derived from primary neuronal tissues and are short
      lived. In order to extend the shelf life of neuronal networks for use in a
      fieldable sensor technology, a renewable source of networks is needed. Neural
      stem and progenitor cells are capable of self-renewal and differentiation into
      functional neuronal networks. The purpose of this study was to develop a strategy
      for growing passaged neural stem and progenitor cells on MEAs under controlled
      conditions to produce differentiated neurons and glia comprising functional
      neuronal networks. Primary and passaged neuroepithelial stem and progenitor cells
      dissociated from embryonic day 13 rat cortex were seeded on MEAs and maintained
      with serum-free medium containing basic fibroblast growth factor (bFGF) combined
      with brain-derived neurotrophic factor (BDNF). These culture conditions lead to
      abundant neurons, with astrocytes as supportive cells, forming synaptically
      linked networks of neurons. Spontaneous action potentials were best recorded from
      networks derived from primary or passaged progenitor cells 4-5 weeks after
      initial culture. The passaged progenitor cell-derived networks on MEAs responded
      to the GABA(A) antagonist bicuculline, the NMDA glutamate inhibitor APV, and the
      non-NMDA glutamate antagonist CNQX indicating active synapses were present.
      Passaged neural stem and progenitor cell-derived networks on MEAs have properties
      similar to networks derived from primary neuronal cultures and can serve as a
      renewable supply of sensor elements for detection of environmental threats.

PMID- 19162464
TI  - Zirconium immobilized on gold-mercaptopropionic acid self-assembled monolayer for
      trace determination of phosphate in blood serum by using CV, EIS, and OSWV.
AB  - Preparation, characterization, and application of a new sensor for the
      determination of phosphate in blood serum is described by cyclic voltammetry
      (CV), electrochemical impedance spectroscopy (EIS), and osteryoung square wave
      voltammetry (OSWV) in the presence of an appropriate redox reaction probe. The
      sensor was based on ionic adsorption of phosphate on Zr(IV) immobilized on gold
      mercaptopropionic acid self-assembled monolayer (Au-MPA-Zr(IV) SAM) electrode.
      Parameters influencing the method were optimized. A linear range calibration
      curve from 1.0 x 10(-7) to 1.0 x 10(-6)M PO(4)(3-) with a detection limit of 5.30
      x 10(-8)M and mean of relative standard deviations (R.S.D.) of 2.75% for n=4 was
      observed in the best conditions by OSWV. Possible interferences from the
      coexisting ions were also investigated. The results demonstrated that sensor
      could be used for the determination of phosphate in the presence of various ions.
      Regeneration of the surface was carried out successfully by 5-min sonication in
      0.1M KOH solution and then 1-min incubation in 1.0x10(-3)M Zr(IV) with a good
      reproducibility, R.S.D.=1.47% for n=4 by OSWV. The validity of the method and
      applicability of the sensor were successfully tested by detection of phosphate in
      blood serum after deproteinization of sample without interference from sample
      matrix. The long-term storage stability of the electrode was studied. The
      experimental data is presented and discussed from which the new sensor is
      characterized.

PMID- 19162465
TI  - STD sensor based on nucleic acid functionalized nanostructured polyaniline.
AB  - STD (sexually transmitted disease, Gonorrhoea) sensor based on nucleic acid probe
      (from Opa, a multi-copy gene of Neisseria gonorrhoeae) functionalized
      nanostructured-polyaniline coated onto indium-tin-oxide-coated glass plate has
      been fabricated using avidin-biotin as cross-linking agent. This DNA
      functionalized electrode can specifically detect upto 0.5 x 10(-15)M of
      complementary target within 60s of hybridization time at 25 degrees C by
      differential pulse voltammetry (DPV) using methylene blue as electro-active DNA
      hybridization indicator. This highly sensitive and specific nucleic acid
      functionalized nanostructured-polyaniline electrode can distinguish presence of
      N. gonorrhoeae from Neisseria meningitidis and Escherichia coli culture and
      spiked samples from the urethral swabs of the patients.

PMID- 19162466
TI  - A liquid crystal-based sensor for real-time and label-free identification of
      phospholipase-like toxins and their inhibitors.
AB  - We report a liquid crystal (LC)-based sensor for real-time and label-free
      identification of phospholipase-like toxins. Beta-bungarotoxin exhibits Ca(2+)
      dependent phospholipase A(2) activity whereas alpha-bungarotoxin and myotoxin II
      do not exhibit any phospholipase activity. The sensor can selectively identify
      beta-bungarotoxin, when it hydrolyzes a phospholipid monolayer self-assembled at
      aqueous-LC interface, through orientational responses of LCs. As a result,
      optical signals that reflect the spatial and temporal distribution of
      phospholipids during the hydrolysis can therefore be generated in a real-time
      manner. The sensor is very sensitive and requires less than 5pg of beta
      bungarotoxin for the detection. When phospholipase A(2) inhibitors are introduced
      together with beta-bungarotoxin, no orientational response of LCs can be
      observed. In addition, the regeneration of the sensor can be done without
      affecting the sensing performance. This work demonstrates a simple and cost
      effective LC-based sensor for identifying phospholipase-like toxins and for
      screening compound libraries to find potential toxin inhibitors.

PMID- 19162467
TI  - Easy modification of glassy carbon electrode for simultaneous determination of
      ascorbic acid, dopamine and uric acid.
AB  - A glassy carbon electrode (GCE) has been modified by electrochemical oxidation in
      mild acidic media (0.1 mol l(-1) H(2)SO(4)) and could be applied for individual
      and simultaneous determination of ascorbic acid (AA), dopamine (DA) and uric acid
      (UA). Oxidized GCE shows a single redox couple (E(0)'=-2.5 mV) which is based on
      the formation functional groups during the electrochemical pretreatment process.
      Proposed GCE successfully decreases the over potentials for the oxidation process
      of these species (AA, DA and UA) comparing with bare GCE. The oxidized GCE has
      its own simplicity, stability, high sensitivity and possesses the potential for
      simultaneous determination of AA, DA and UA.

PMID- 19162468
TI  - ED95 of phenylephrine to prevent spinal-induced hypotension and/or nausea at
      elective cesarean delivery.
AB  - BACKGROUND: The purpose of this trial was to determine the 95% effective dose
      (ED95) of phenylephrine by intermittent i.v. bolus, to prevent spinal-induced
      hypotension and/or nausea at elective cesarean delivery. METHODS: The study was
      conducted in a double-blinded fashion in 50 patients undergoing elective cesarean
      delivery under spinal anesthesia. The dose of phenylephrine was determined using
      up-down sequential allocation, modified by a variation of the Narayana rule.
      Systolic pressure and heart rate were assessed every minute until uterine
      incision. The first patient was assigned a 40-microg dose, and the dose to
      subsequent patients varied by 10-microg increments or decrements. An adequate
      response was defined as absence of hypotension (systolic pressure <80% of
      baseline) and nausea. The study solution was given immediately after spinal
      administration, without prior pressure measurement, and thereafter when the
      systolic pressure was <or=control values. fell below baseline. The ED95 was
      determined by a logistic model with non-log-transformed doses, using Firth's
      penalized maximum likelihood method with 95% confidence intervals based on
      penalized profile likelihood. RESULTS: The ED95 of phenylephrine was estimated as
      159 microg (95% confidence interval: 122-371 microg), although the largest dose
      given in the study was only 120 microg. Hypertension (systolic blood pressure
      >120% of baseline) was observed in 14 cases, immediately after intrathecal
      injection and prophylactic phenylephrine administration in all cases. CONCLUSION:
      The ED95 of phenylephrine, administered as intermittent boluses to prevent pre
      delivery spinal-induced hypotension and/or nausea at elective cesarean delivery,
      is at least 122 microg (lower limit of the confidence interval). The safety of
      this dose warrants further studies.

PMID- 19162469
TI  - Antenatal blood patch in a pregnant woman with spontaneous intracranial
      hypotension.
AB  - Spontaneous intracranial hypotension is a condition that presents with postural
      headaches similar to those caused by accidental dural puncture. The diagnosis is
      based on clinical presentation, cerebrospinal fluid evaluation and magnetic
      resonance imaging scanning. We present a case of spontaneous intracranial
      hypotension with typical clinical and magnetic resonance imaging findings in a
      pregnant patient who was treated with an epidural blood patch. The blood patch,
      performed at 32 weeks of gestation, produced transient improvement in symptoms
      but failed to completely cure the headache, which worsened over the next few
      days. Symptoms resolved over the subsequent three weeks with conservative
      therapy.

PMID- 19162470
TI  - Protein acrobatics in pairs--dimerization via domain swapping.

PMID- 19162471
TI  - Biophysical characterization of intrinsically disordered proteins.
AB  - The challenges associated with the structural characterization of disordered
      proteins have resulted in the application of a host of biophysical methods to
      such systems. NMR spectroscopy is perhaps the most readily suited technique for
      providing high-resolution structural information on disordered protein states in
      solution. Optical methods, solid state NMR, ESR and X-ray scattering can also
      provide valuable information regarding the ensemble of conformations sampled by
      disordered states. Finally, computational studies have begun to assume an
      increasingly important role in interpreting and extending the impact of
      experimental data obtained for such systems. This article discusses recent
      advances in the applications of these methods to intrinsically disordered
      proteins.

PMID- 19162473
TI  - Natural orifice transluminal endoscopic surgery (N.O.T.E.S.) for neoplasia of the
      chest and mediastinum.
AB  - Indications for Natural Orifice Transluminal Endoscopic Surgery or NOTES have so
      far mainly concerned intra-abdominal surgery. The next question to be addressed
      was whether this access can be extended into other body cavities and, in
      particular, whether there is a significant role for NOTES above the diaphragm?
      Using the esophagus, one of the mediastinal organs, as a direct carrier to access
      the mediastinum and the pleural cavity would eliminate the dissection of the
      pretracheal fascia required by mediastinoscopy and would give access to the inner
      part of lung parenchyma. Alternatively, transgastric (or even transvaginal)
      transhiatal approaches could supplement standard operative techniques in order to
      minimize abdominal wall ingression. Furthermore, conventional techniques seem
      disproportionate measures for relatively simple procedures such as evaluating the
      outcome of chemotherapy and restaging of medically treated mediastinal lesions.
      As a truly minimal access technique, NOTES could therefore find new indications
      for intervention. The obvious limiting factor in all of this is assurance of
      'leak proof' mural closure. However, if safety of access-site sealing can be
      established in clinical studies, we could have found an easier, reproducible
      alternative to the access to mediastinum. This review examines the rationale and
      evidence for proposing such a venture and deliberates its likely clinical
      applicability and thereby its potential to become a reality.

PMID- 19162472
TI  - Computational evaluation of protein-small molecule binding.
AB  - Determining protein-small molecule binding affinity is a key component of present
      day rational drug discovery. To circumvent the time, labor, and materials costs
      associated with experimental protein-small molecule binding assays, a variety of
      structure-based computational methods have been developed for determining protein
      small molecule binding affinities. These methods can be placed in one of two
      classes: accurate but slow (Class 1), and fast but approximate (Class 2). Class 1
      methods, which explicitly take into account protein flexibility and include an
      atomic-level description of solvation, are capable of quantitatively reproducing
      experimental protein-small molecule absolute binding free energies. However,
      Class 1 computational requirements make screening thousands to millions of small
      molecules against a protein, as required for rational drug design, infeasible for
      the foreseeable future. Class 2 methods, on the contrary, are sufficiently fast
      to perform such inhibitor screening, yet they suffer from limited descriptions of
      protein flexibility and solvation, which in turn limit their ability to select
      and rank-order small molecules by computed binding affinities. This review
      presents an overview of Class 1 and Class 2 methods, and avenues of research in
      Class 2 methods aimed at bringing them closer to Class 1 accuracy.

PMID- 19162474
TI  - Biodegradation by activated sludge and toxicity of tetracycline into a semi
      industrial membrane bioreactor.
AB  - Much attention has been devoted recently to the fate of pharmaceutically active
      compounds such as tetracycline antibiotics in soil and water. Tetracycline (TC)
      biodegradability by activated sludge derived from membrane bioreactor (MBR)
      treating swine wastewater via CO(2)-evolution was evaluated by means of modified
      Sturm test, which was also used to evaluate its toxicity on carbon degradation.
      The impact of tetracycline on a semi-industrial MBR process was also examined and
      confronted to lab-scale experiments. After tetracycline injection in the pilot,
      no disturbance was detected on the elimination of organic matters and ammonium
      (nitrification), reaching after injection 88% and 99% respectively; only
      denitrification was slightly affected. Confirming the ruggedness and the
      superiority of membrane bioreactors over conventional bioreactors, no toxicity
      was observed at the considered level of TC in the pilot (20 mg TOC L(-1)), while
      at lab-scale sodium benzoate biodegradation was completely inhibited from 10 mg
      TOC L(-1) TC. The origin of the activated sludge showed a significant impact on
      the performances, since the ultimate biodegradation was in the range -50% to -53%
      for TC concentrations in the range 10-20 mg TOC L(-1) with conventional
      bioreactor sludge and increased to 18% for 40 mg TOC L(-1) of TC with activated
      sludge derived from the MBR pilot. This confirmed the higher resistance of
      activated sludge arising from membrane bioreactor.

PMID- 19162475
TI  - Characterization of a metal resistant Pseudomonas sp. isolated from uranium mine
      for its potential in heavy metal (Ni2+, Co2+, Cu2+, and Cd2+) sequestration.
AB  - Heavy metal sequestration by a multimetal resistant Pseudomonas strain isolated
      from a uranium mine was characterized for its potential application in metal
      bioremediation. 16S rRNA gene analysis revealed phylogenetic relatedness of this
      isolate to Pseudomonas fluorescens. Metal uptake by this bacterium was
      monophasic, fast saturating, concentration and pH dependent with maximum loading
      of 1048 nmol Ni(2+) followed by 845 nmol Co(2+), 828 nmol Cu(2+) and 700 nmol
      Cd(2+)mg(-1) dry wt. Preferential metal deposition in cell envelope was confirmed
      by TEM and cell fractionation. FTIR spectroscopy and EDX analysis revealed a
      major role of carboxyl and phosphoryl groups along with a possible ion exchange
      mechanism in cation binding. Binary system demonstrated selective metal binding
      affinity in the order of Cu(2+)>Ni(2+)>Co(2+)>Cd(2+). A comparison with similar
      metal uptake reports considering live bacteria strongly indicated the superiority
      of this strain in metal sequestration, which could be useful for developing
      efficient metal removal system.

PMID- 19162476
TI  - Siderophore production by the marine-derived Aureobasidium pullulans and its
      antimicrobial activity.
AB  - Over 300 yeast strains isolated from different marine environments were screened
      for their ability to produce siderophore. Among them, only the yeast strain HN6.2
      which was identified to be Aureobasidium pullulans was found to produce high
      level of the siderophore. Under the optimal conditions, this yeast strain could
      produce 1.1mg/ml of the siderophore. The crude siderophore produced by the yeast
      strain HN6.2 was able to inhibit cell growth of Vibrio anguillarum and Vibrio
      parahaemolyticus, isolated from the diseased marine animals.

PMID- 19162477
TI  - A novel class of allosteric modulators of AMPA/Kainate receptors.
AB  - The rapid hydrolysis in vivo of IDRA21 to 2-amino-5-chlorobenzensulfonamide has
      been demonstrated by microdialysis experiments. The IDRA21 metabolite possess in
      vitro a biological activity similar to that of IDRA21 itself. Taking 2-amino-5
      chlorobenzensulfonamide as lead compound, a novel class of AMPAR positive
      allosteric modulators has been prepared.

PMID- 19162478
TI  - Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a
      novel BCS1L mutation in an isolated complex III-deficient patient.
AB  - Mutations in BCS1L, a respiratory chain complex III assembly chaperone,
      constitute a major cause of mitochondrial complex III deficiency and are
      associated with GRACILE and Bjornstad syndromes. Here we describe a 4-year-old
      infant with hyperlactacidemia, mild liver dysfunction, hypotonia, growth and
      psychomotor retardation, dysmorphic features and mitochondrial complex III
      deficiency. Respiratory chain enzyme activities showed an isolated complex III
      defect in muscle and fibroblasts. Sequencing and polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis revealed a novel
      homozygous BCS1L mutation, c.148A>G, which caused a p.T50A substitution at an
      evolutionarily conserved BCS1L region. The severity of the complex III enzyme
      defect correlated with decreased amounts of BCS1L and respiratory chain complex
      III in the affected tissues. Our findings support a pathogenic role for the novel
      BCS1L mutation in a patient with a singular clinical phenotype.

PMID- 19162480
TI  - Staphylococcus aureus as an intracellular pathogen: the role of small colony
      variants.
AB  - Increasing evidence indicates that Staphylococcus aureus might be a facultative
      intracellular pathogen. In particular, certain subpopulations, called small
      colony variants (SCVs), seem to be well adapted to the intracellular milieu. When
      compared to 'normal' staphylococcal strains, SCVs show increased uptake by host
      cells, resistance to intracellular defenses and reduced stimulation of host
      defenses. We propose that the ability to form two subpopulations with different
      phenotypes might allow S. aureus the option for both extra- cellular and intra
      cellular survival in the host.

PMID- 19162479
TI  - Novel activation domain derived from Che-1 cofactor coupled with the artificial
      protein Jazz drives utrophin upregulation.
AB  - Our aim is to upregulate the expression level of the dystrophin related gene
      utrophin in Duchenne muscular dystrophy, thus complementing the lack of
      dystrophin functions. To this end, we have engineered synthetic zinc finger based
      transcription factors. We have previously shown that the artificial three-zinc
      finger protein named Jazz fused with the Vp16 activation domain, is able to bind
      utrophin promoter A and to increase the endogenous level of utrophin in
      transgenic mice. Here, we report on an innovative artificial protein, named CJ7,
      that consists of Jazz DNA binding domain fused to a novel activation domain
      derived from the regulatory multivalent adaptor protein Che-1/AATF. This
      transcriptional activation domain is 100 amino acids in size and it is very
      powerful as compared to the Vp16 activation domain. We show that CJ7 protein
      efficiently promotes transcription and accumulation of the acetylated form of
      histone H3 on the genomic utrophin promoter locus.

PMID- 19162481
TI  - Genomic islands are dynamic, ancient integrative elements in bacterial evolution.
AB  - Acquisition of genomic islands plays a central part in bacterial evolution as a
      mechanism of diversification and adaptation. Genomic islands are non-self
      mobilizing integrative and excisive elements that encode diverse functional
      characteristics but all contain a recombination module comprised of an integrase,
      associated attachment sites and, in some cases, a recombination directionality
      factor. Here, we discuss how a group of related genomic islands are
      evolutionarily ancient elements unrelated to plasmids, phages, integrons and
      integrative conjugative elements. In addition, we explore the diversity of
      genomic islands and their insertion sites among Gram-negative bacteria and
      discuss why they integrate at a limited number of tRNA genes.

PMID- 19162482
TI  - Preventing biofilms of clinically relevant organisms using bacteriophage.
AB  - Biofilms might result in healthcare-associated infections and substantially
      impact healthcare delivery. Bacteriophage (phage) has been used to treat
      infectious diseases in humans and there is interest in phage to control biofilms.
      Phages propagate in their bacterial host and many phages produce depolymerases
      that hydrolyze biofilm extracellular polymers. Drawbacks of phage to consider
      include narrow host range, bacterial resistance to phage and phage-encoded
      virulence genes that can incorporate into the host bacterial genome. The immune
      system might inactivate phage, and impure phage preparations could contain
      endotoxin. Phage mixtures or engineered phages could provide effective strategies
      to overcome these obstacles. Lytic bacteriophages could become a new class of
      anti-biofilm agents.

PMID- 19162483
TI  - The developmental model of microbial biofilms: ten years of a paradigm up for
      review.
AB  - For the past ten years, the developmental model of microbial biofilm formation
      has served as the major conceptual framework for biofilm research; however, the
      paradigmatic value of this model has begun to be challenged by the research
      community. Here, we critically evaluate recent data to determine whether biofilm
      formation satisfies the criteria requisite of a developmental system. We contend
      that the developmental model of biofilm formation must be approached as a model
      in need of further validation, rather than utilized as a platform on which to
      base empirical research and scientific inference. With this in mind, we explore
      the experimental approaches required to further our understanding of the biofilm
      phenotype, highlighting evolutionary and ecological approaches as a natural
      complement to rigorous mechanistic studies into the causal basis of biofilm
      formation. Finally, we discuss a second model of biofilm formation that serves as
      a counterpoint to our discussion of the developmental model. Our hope is that
      this article will provide a platform for discussion about the conceptual
      underpinnings of biofilm formation and the impact of such frameworks on shaping
      the questions we ask, and the answers we uncover, during our research into these
      microbial communities.

PMID- 19162484
TI  - Benzopyridooxathiazepine derivatives as novel potent antimitotic agents.
AB  - Herein, we describe the structure-activity relationship study of a new 1
      (arylalkyl)-11H-benzo[f]-1,2-dihydropyrido[3,2,c][1,2,5]oxathiazepine 5,5-dioxide
      series of antimitotic agents. The pharmacological results obtained from previous
      works allowed us to identify compound 1 as a new cytotoxic agent inhibiting
      tubulin polymerization. We have undertaken the synthesis of its non-methylated
      analogue 7 and have extended our investigations to a novel, structurally related
      benzopyridooxathiazepine dioxide series. Among all analogues synthesized in this
      study, compound 10b was the most promising, being 12-fold more potent than
      compound 1. Its activity over a panel of five tumoral cell lines was in the
      nanomolar range for all of the histological types tested and flow cytometric
      studies performed on L1210 cells showed an accumulation of the cells in the G2/M
      phases of the cell cycle with a significant percentage of tetraploid cells (8N
      DNA content). This interesting pharmacological profile, resulting from inhibition
      of tubulin polymerization, encouraged us to perform preliminary in vivo studies.

PMID- 19162485
TI  - Synthesis of buprestins D, E, F, G and H; structural confirmation and biological
      testing of acyl glucoses from jewel beetles (Coleoptera: Buprestidae).
AB  - A chemical and enzymatic synthesis was developed for five variant buprestins
      termed D, E, F, G and H found in jewel beetles (Coleoptera: Buprestidae).
      Selective acylation of the primary hydroxyl group of beta-D-glucopyranose-1,2
      bis(pyrrole-2-carboxylate) with substituted benzoic or cinnamic acid derivatives
      followed by deprotection gave the target compounds. Using coinjection the
      identity with the natural extracts was confirmed. The activity of the variant
      buprestins as deterrents for ants was assayed.

PMID- 19162486
TI  - Taste-guided identification of high potency TRPA1 agonists from Perilla
      frutescens.
AB  - Perilla frutescens is a food plant widely used in Asian cuisine. This plant was
      investigated for its interesting taste and somatosensory properties.
      Perillaldehyde and perillaketone are among the components of the aromatic
      extracts from P. Frutescens. These compounds were shown here to activate the
      cloned TRPA1 channel when expressed in an heterologous cell system and are
      therefore suggested to be responsible for the chemesthetic properties of this
      plant.

PMID- 19162487
TI  - Biarylether amide quinolines as liver X receptor agonists.
AB  - A series of 4-(amido-biarylether)-quinolines was prepared as potential LXR
      agonists. Appropriate substitution with amide groups provided high affinity LXR
      ligands, some with excellent potency and efficacy in functional assays of LXR
      activity. Novel amide 4g had a binding IC(50)=1.9 nM for LXRbeta and EC(50)=34 nM
      (96% efficacy relative to T0901317) in an ABCA1 gene expression assay in mouse
      J774 cells, demonstrating that 4-(biarylether)-quinolines with appropriate amide
      substitution are potent LXR agonists.

PMID- 19162489
TI  - Synthesis and biological evaluation of some new 1,4-dihydropyridines containing
      different ester substitute and diethyl carbamoyl group as anti-tubercular agents.
AB  - Tuberculosis is a leading infectious cause of death worldwide. Because of the
      concern of the resistance to most of the commonly used drugs displayed by the
      considered mycobacteria, most efforts have been done to introduce new anti
      tubercular agents. Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl
      derivatives with lipophilic groups have significant anti-tubercular activity. In
      this study, we synthesized new derivatives of 1,4-dihydropyridines in which
      different alkyl and aryl esters and diethyl carbamoyl are substituted in C-3 and
      C-5 of the DHP ring. In addition nitroimidazole ring is substitutes at C-4
      position. These asymmetric analogues were synthesized by a modified Hantzsh
      reaction using procedure reported by Meyer. The in vitro anti-tubercular activity
      of compounds against Mycobacterium tuberculosis was evaluated. The results
      indicate that the compounds containing aromatic esters are more potent than alkyl
      ones. The most potent aromatic compound (R=3-phenylpropyl) exhibits comparable
      anti-tubercular activity (MIC=1 micromol/ml) with reference compound isoniazide
      (INH) (MIC=1 micromol/ml). Conformational analysis, SAR studies of these
      compounds showed that increasing in lipophilicity and rotable bonds of these
      compounds resulted in increasing anti-tubercular activity.

PMID- 19162488
TI  - Design, synthesis and biological evaluation of novel dual inhibitors of
      acetylcholinesterase and beta-secretase.
AB  - To explore novel effective drugs for the treatment of Alzheimer's disease (AD), a
      series of dual inhibitors of acetylcholineterase (AChE) and beta-secretase (BACE
      1) were designed based on the multi-target-directed ligands strategy. Among them,
      inhibitor 28 exhibited good dual potency in enzyme inhibitory potency assay (BACE
      1: IC(50)=0.567 microM; AChE: IC(50)=1.83 microM), and also showed excellent
      inhibitory effects on Abeta production of APP transfected HEK293 cells
      (IC(50)=98.7 nM) and mild protective effect against hydrogen peroxide (H(2)O(2))
      induced PC12 cell injury. Encouragingly, intracerebroventricular injection of 28
      into amyloid precursor protein (APP) transgenic mice caused a 29% reduction of
      Abeta(1-40) production. Therefore, 28 was demonstrated as a good lead compound
      for the further study and more importantly, the strategy of AChE and BACE-1 dual
      inhibitors might be a promising direction for developing novel drugs for AD
      patients.

PMID- 19162490
TI  - Cytotoxic palladium complexes of bioreductive quinoxaline N1,N4-dioxide prodrugs.
AB  - Four new palladium(II) complexes with the formula Pd(L)(2), where L are
      quinoxaline-2-carbonitrile N(1),N(4)-dioxide derivatives, were synthesized as a
      contribution to the chemistry and pharmacology of metal compounds with this class
      of pharmacologically interesting bioreductive prodrugs. Compounds were
      characterized by elemental, conductometric and thermogravimetric analyses, fast
      atom bombardment mass spectrometry (FAB-MS) and electronic, Fourier transform
      infrared (FTIR) and (1)H-nuclear magnetic resonance spectroscopies. The complexes
      were subjected to cytotoxic evaluation on V79 cells in hypoxic and aerobic
      conditions. In addition, a preliminary study on interaction with plasmid DNA in
      normoxia was performed. Complexes showed different in vitro biological behavior
      depending on the nature of the substituent on the quinoxaline ring. Pd(L1)(2) and
      Pd(L2)(2), where L1 is 3-aminoquinoxaline-2-carbonitrile N(1),N(4)-dioxide and L2
      is 3-amino-6(7)-methylquinoxaline-2-carbonitrile N(1),N(4)-dioxide, showed non
      selective cytotoxicity, being cytotoxic either in hypoxic or in aerobic
      conditions. On the other hand, Pd(L3)(2), where L3 is 3-amino-6(7)
      chloroquinoxaline-2-carbonitrile N(1),N(4)-dioxide, resulted in vitro more potent
      cytotoxin in hypoxia (P=5.0 microM) than the corresponding free ligand (P=9.0
      microM) and tirapazamine (P=30.0 microM), the first bioreductive cytotoxic drug
      introduced into clinical trials. In addition, it showed a very good selective
      cytotoxicity in hypoxic conditions, being non-cytotoxic in normoxia. Its hypoxic
      cytotoxicity relationship value, HCR, was of the same order than those of other
      hypoxia selective cytotoxins (i.e., Mitomycine C, Misonidazole and the N-oxide
      RB90740). Interaction of the complexes with plasmid DNA in normoxia showed dose
      dependent ability to relax the negative supercoiled forms via different
      mechanisms. Pd(L2)(2) introduced a scission event in supercoiled DNA yielding the
      circular relaxed form. Meanwhile, both Pd(L1)(2) and Pd(L3)(2) produced the loss
      of negative supercoils rendering a family of topoisomers with reduced
      electrophoretic mobility. Pd(L3)(2) showed a more marked effect than Pd(L1)(2).
      Indeed, for the highest doses assayed, Pd(L3)(2) was even able to introduce
      positive supercoils on the plasmid DNA.

PMID- 19162491
TI  - A simple modification of GE tracerlab FX C Pro for rapid sequential preparation
      of [11C]carfentanil and [11C]raclopride.
AB  - A simple modification of the GE Tracerlab FX C Pro system which enabled
      performance of both solvent capture (loop method) and conventional solution phase
      [(11)C]methylation in the same module is described. By the quick setup and
      automated method, [(11)C]carfentanil and [(11)C]raclopride could be prepared in
      rapid succession without opening the hot cell. The radiochemical yields were over
      40% and 30% (decay-corrected and based on [(11)C]methyl iodide) for
      [(11)C]carfentanil and [(11)C]raclopride, respectively. The radiochemical
      purities were greater than 95% and specific activities over 5 Ci/mmol for both
      tracers. The modification is extremely easy and can be utilized for multiple
      syntheses of other (11)C-labeled radiopharmaceuticals in a fast and reliable
      manner.

PMID- 19162492
TI  - GMP-compliant radiosynthesis of [18F]altanserin and human plasma metabolite
      studies.
AB  - [(18)F]altanserin is the preferred radiotracer for in-vivo labeling of serotonin
      2A receptors by positron emission tomography (PET). We report a modified
      synthesis procedure suited for reliable production of multi-GBq amounts of
      [(18)F]altanserin useful for application in humans. We introduced thermal heating
      for drying of [(18)F]fluoride as well as for the reaction instead of microwave
      heating. We furthermore describe solid phase extraction and HPLC procedures for
      quantitative determination of [(18)F]altanserin and metabolites in plasma. The
      time course of arterial plasma activity with and without metabolite correction
      was determined. 90 min after bolus injection, 38.4% of total plasma activity
      derived from unchanged [(18)F]altanserin. Statistical comparison of kinetic
      profiles of [(18)F]altanserin metabolism in plasma samples collected in the
      course of two ongoing studies employing placebo, the serotonin releaser
      dexfenfluramine and the hallucinogen psilocybin, revealed the same tracer
      metabolism. We conclude that metabolite analysis for correction of individual
      plasma input functions used in tracer modeling is not necessary for
      [(18)F]altanserin studies involving psilocybin or dexfenfluramine treatment.

PMID- 19162493
TI  - Cation exchange separation of 61Cu2+ from natCo targets and preparation of 61Cu
      DOTA-HSA as a blood pool agent.
AB  - An improved method for isolation of (61)Cu(2+) from a (nat)Co target using cation
      exchange was developed. (61)Cu(2+) was eluted from a cation exchange resin column
      by 0.2 M HCl with 90% acetone, while Co(2+) remained on the column. The whole
      separation process was completed within 50 min at more than 72% yield. The Co(2+)
      impurity level in (61)Cu(2+) solution was reduced to less than 0.1 ppm. Highly
      pure (61)Cu(2+) solution was then applied to prepare (61)Cu-1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-human serum albumin (HSA)
      which showed good blood pool imaging properties.

PMID- 19162494
TI  - Immuno-chemotherapy reduces recurrence of malignant pleural mesothelioma: an
      experimental setting.
AB  - OBJECTIVE: To assess the effect of immuno-chemotherapy on the extent of local
      tumour recurrence in an established rat model of malignant pleural mesothelioma
      (MPM). METHODS: Six days after subpleural inoculation of a syngeneic MPM cell
      line Interleukin-45 (IL-45), left-sided pneumonectomy and resection of the tumour
      nodule was performed. Animals were randomised into four treatment groups for
      intrapleural therapy: control (n=6), 500 microg cytosine phosphate guanosine
      oligodeoxynucleotide (CpG-ODN) (n=6), cisplatin-fibrin (n=6), cisplatin
      fibrin+500 microg CpG (n=6). Six days later the volume of tumour recurrence was
      assessed, which was the primary endpoint. Secondary endpoints were quantification
      of the ratio host/tumour cells in the local recurrence and cytokine expression
      profile in the tumour tissue by real time quantitative PCR (qPCR). T lymphocyte
      subpopulations in the tumour recurrence tissue were evaluated by
      immunohistochemistry. Treatment-related toxicity was monitored by measuring blood
      chemistry and complete blood count. RESULTS: The volume of tumour recurrence was
      significantly reduced from 610 mm(3) in the control group to 11.7 mm(3) in the
      cisplatin-fibrin group (p=0.004) and to 21.8mm(3) in the cisplatin-fibrin+CpG
      group (p=0.004). Pro-inflammatory cytokines (Interferon-gamma (IFN-gamma),
      Interleukin-6 (IL-6), Interleukin-12 (IL-12)) were increased after treatment with
      cisplatin-fibrin+CpG in comparison to cisplatin-fibrin alone but differences were
      not statistically significant. We found a higher ratio of host/tumour cells in
      the cisplatin-fibrin+CpG group (45/55%) compared to the cisplatin-fibrin group
      (27/73%). In comparison to the control group, animals treated with cisplatin
      fibrin+CpG showed a higher number of CD8+ T-cells in the tumour tissue. No
      significant treatment-related toxicity was observed. CONCLUSIONS: Adjuvant
      treatment with chemotherapy or immuno-chemotherapy leads to significant reduction
      of mesothelioma recurrence after surgery in this rat MPM model. Immuno
      chemotherapy resulted in an increased recruitment of inflammatory cells to the
      site of tumourigenesis and elicited higher level of tumour growth inhibiting
      cytokines.

PMID- 19162495
TI  - Pseudoaneurysm following Dacron replacement of the ascending aorta.

PMID- 19162496
TI  - Prediction of pulmonary function after lung lobectomy by subsegments counting,
      computed tomography, single photon emission computed tomography and computed
      tomography: a comparative study.
AB  - OBJECTIVE: The aim of the present study was to determine the optimal method of
      predicting postoperative pulmonary function (PPF) after lung lobectomy. METHODS:
      The forced expiratory volume in 1s (FEV(1)) was measured in 37 patients before
      and after lobectomy, and the following three methods of predicting the PPF were
      evaluated: (1) the number of functioning subsegments to be resected were counted
      (subsegments counting [SC]); (2) the volume of the functioning lung was
      calculated using CT images (quantitative CT); and (3) perfusion scintigraphy was
      performed using co-registered single photon emission computed tomography and CT
      imaging (SPECT/CT). The FEV(1) values predicted using these three methods were
      then compared with the measured postoperative FEV(1), and the correlations and
      differences were analyzed. RESULTS: While a paired t-test showed the SPECT/CT
      method to have the smallest difference between the measured and the predicted
      FEV(1) values (0.05 l, p=0.33), followed by the quantitative CT method (0.07 l,
      p=0.07), and finally the SC method (0.15 l, p<0.001), the difference between the
      two values was not significantly different between the quantitative CT and
      SPECT/CT method (p=0.22). CONCLUSIONS: While the SC method is inferior to both
      the quantitative CT and the SPECT/CT methods for predicting the PPF after
      lobectomy, the latter two methods are almost equally accurate.

PMID- 19162497
TI  - Nonrheumatic calcific aortic stenosis: an overview from basic science to
      pharmacological prevention.
AB  - Calcific aortic stenosis is a frequent degenerative disease, which represents the
      most common indication for adult heart valve surgery, and carries substantial
      morbidity and mortality. Due to ageing populations in western countries, its
      prevalence is expected to increase in the coming years. Basic science studies
      suggest that the progression of aortic valve stenosis involves an active
      biological process, and that the molecular mechanisms promoting this development
      resemble those of atherosclerosis, as stenotic aortic valves are characterized by
      complex histological lesions, consisting of activated inflammatory cells, lipid
      deposits, extracellular matrix remodeling, calcific nodules, and bone tissue.
      This has led to the hypothesis that drugs effective in delaying atherosclerosis
      progression (e.g. statins) might also be able to prevent the progression of
      calcific aortic valve stenosis. The potential benefit of statin therapy, however,
      is controversial and widely debated, as recent randomized studies done in
      patients with moderate to severe degrees of aortic stenosis failed to
      consistently show substantial benefits of this class of drugs. This review
      focuses on various aspects of molecular mechanisms underlying calcific aortic
      valve stenosis and discusses recent experimental and clinical studies that
      address the potential benefit of targeted drug therapies. Taken together, current
      evidence suggests that the progression of calcific aortic stenosis is a multi
      factorial process; the multitude of the mechanisms potentially involved in aortic
      valve stenosis indicates that drug therapy aimed at reducing its progression is
      necessarily multi-factorial and should address the earliest stages of the
      disease, as it is now evident that pharmacological treatment administered in more
      advanced stages of the disease may be ineffective or, at best, much less
      effective.

PMID- 19162498
TI  - Surgical treatment of primary palmar hyperhidrosis: a prospective randomized
      study comparing T3 and T4 sympathicotomy.
AB  - OBJECTIVE: Endoscopic thoracic sympathetic surgery was effective for palmar
      hyperhidrosis (PH), but side effects such as compensatory sweating and over dry
      hands were common. A multiple centers prospective randomized study was designed
      to compare the efficiency and side effects of T3 and T4 sympathicotomy in the
      treatment of PH. METHODS: From September 2004 to February 2006, 141 consecutive
      patients with PH were randomized into two therapeutic groups: group T3 underwent
      T3 sympathicotomy (n=68) and group T4 underwent T4 sympathicotomy (n=73).
      Improvement of hand sweating, side effects like compensatory sweating or over dry
      hands, and satisfactory rate of the patients were recorded. RESULTS: There were
      78 males and 63 females. The median age was 26.9 years. The two groups were
      comparable in gender, age, severity of sweating and average period of follow-up.
      All operations were successful with no severe complications or perioperative
      mortality. A 17.8+/-7.9 month follow-up showed that palmar sweating improved in
      all patients and the effective rate was 100%. Mild moist hands occurred more
      frequent in group T4 than in group T3 (59.4% vs 25.8%, p<0.0001). Most involved
      patients were 'very satisfied' with this result except for four patients (5.8%)
      in group T4; incidences of compensatory sweating and over dry hands were both
      lower in group T4 than in group T3 (56.5% vs 77.4%, p=0.011 and 1.4% vs 12.9%,
      p=0.013, respectively). Moderate compensatory sweating (CS) occurred in 14.5% in
      group T3 and 2.9% in group T4 (p=0.017). 'Very satisfied' rate was higher in
      group T4 than in group T3 (p<0.0001) while 'partially satisfied' rate was
      comparable between the two groups. CONCLUSION: T3 and T4 sympathicotomies are
      both effective for the treatment of PH. T4 sympathicotomy, decreases the side
      effects but do not compromise the therapeutic effects, and should be the method
      of choice.

PMID- 19162500
TI  - Fractional flow reserve: a reliable tool in bypass strategy.

PMID- 19162501
TI  - Chest wall desmoid tumor with life-threatening intrathoracic extension.

PMID- 19162502
TI  - Can absorbable stabilizers be used routinely in the Nuss procedure?
AB  - OBJECTIVE: During minimal invasive surgical correction of pectus excavatum the
      metal bar is rotated 180 degrees and fixed by one or two stabilisers. Previously,
      all stabilisers were made from metal, but they often caused chronic pain and had
      to be removed. Recently, a slowly absorbable stabiliser made from Lactosorb has
      been introduced. METHODS: From 2001 to 2008 a total of 507 patients underwent
      minimally invasive repair of pectus excavatum at Aarhus University Hospital.
      Since February 2007 we routinely used absorbable stabilisers made by Lactosorb.
      We always used shorter pectus bars than originally suggested and always placed
      one stabiliser close to the entry in the thoracic cavity on the left side. All
      operations were performed by the same surgeon and all patients were seen 6 weeks
      after surgery. Patient records were reviewed for retrospective analysis. RESULTS:
      In 422 patients we used a metal stabiliser while 85 patients received a Lactosorb
      stabilizer. Seven patients received two stabilisers. During the follow-up period
      one metal stabiliser broke after 2(1/2) years (0.2%), but within 6 weeks after
      surgery three Lactosorb stabilizers broke (3.5%) and another three dislocated
      laterally (3.5%). CONCLUSIONS: Absorbable stabilisers may be used for minimal
      invasive surgery for pectus excavatum but they are more vulnerable and break
      easier than metal stabilisers. This is likely a consequence of high stress forces
      that may be more pronounced in patients who receive a shorter pectus bar, but
      further research is needed.

PMID- 19162503
TI  - Analysis of collateral blood flow to the lower body during selective cerebral
      perfusion: is three-vessel perfusion better than two-vessel perfusion?
AB  - OBJECTIVE: During selective cerebral perfusion (SCP), only the upper body is
      perfused. However, blood actually returns into the descending aorta through
      collaterals during SCP. This collateral blood flow (CBF) is thought to be
      important to protect the visceral organs and spinal cord from ischemia. The left
      subclavian artery is postulated to be important as a collateral source to the
      lower body. Therefore, we measured CBF and examined whether a perfusion technique
      (three- or two-vessel perfusion) affects CBF to the lower body during SCP.
      METHODS: CBF was measured in 49 patients who underwent aortic arch surgery with
      SCP between August 2006 and July 2008. CBF, the amount of blood returning into
      the descending aorta during SCP, was measured under conditions of constant flow
      during SCP, with three-vessel cannulation that included the left subclavian
      artery, or with two-vessel cannulation that excluded the left subclavian artery.
      To prove visceral perfusion during SCP, hepatic (n=22) and stomach (n=5) tissue
      blood flows were measured using a laser-Doppler flowmeter. RESULTS: The mean
      perfusion flow rate during SCP was 804+/-91ml/min. The mean CBF under three
      vessel perfusion (53+/-34ml/min, 6.5+/-3.8% of SCP) was significantly (p<0.0001)
      higher compared with that under two-vessel perfusion (43+/-29ml/min, 5.3+/-3.1%
      of SCP). There was substantial perfusion in the visceral organs during SCP as
      determined by laser-Doppler flowmeter. CONCLUSION: Visceral organs were perfused
      to some extent through collaterals and protected from ischemia during SCP. Left
      subclavian arterial perfusion enabled significant CBF to the lower body.
      Considering this CBF, three-vessel perfusion appears to be better than two-vessel
      perfusion during SCP; however, the choice of perfusion technique may not be so
      important under conditions of hypothermia because the difference in CBF between
      the two methods was small.

PMID- 19162504
TI  - Right coronary artery giant aneurysm.

PMID- 19162505
TI  - Characterization of self-assembly of Euplotes octocarinatus centrin.
AB  - Centrin, an EF-hand calcium-binding protein with high homology to calmodulin
      (CaM), is an essential component for microtubule-organizing center (MTOC) in
      organisms ranging from algae and yeast to human. It plays an important structural
      role by contributing to the formation of Ca(2+)-sensitive contractile filaments
      and some super-molecular assemblies. Previous work suggests that the N-terminal
      domain of centrin especially its first 20-residue fragment, is required for the
      self-assembly of protein. Native polyacrylamide gel electrophoresis (native
      PAGE), pull-down assay, fluorescence resonance light scattering (RLS) and yeast
      two-hybrid assay indicate that the C-terminal domain of Euplotes octocarinatus
      centrin (EoCen) also contributes to the centrin self-assembly besides its N
      terminal domain in vivo and in vitro. On the basis of our results, a self
      assembly mode of centrin, which is C-to-C as well as N-to-N (between C- and C
      terminal domains as well as between N- and N-terminal domains), is put forward
      providing maybe some insights into the molecular mechanism of centrin functions
      in the cell.

PMID- 19162506
TI  - Oxidative stress enzymes in Ficus religiosa L.: biochemical, histochemical and
      anatomical evidences.
AB  - In order to unveil the reasons behind the successful survival of Ficus religiosa
      L. grown under normal and adverse habitats (AH), i.e., on concrete roof tops were
      subjected to biochemical, histochemical and physiological studies with a focus on
      reactive oxygen species (ROS) and oxidative stress enzymes (OSE). The specific
      objectives were: to localize the OSE, peroxidase (POX) and catalase (CAT); to
      localize and quantify the main ROS, hydrogen peroxide (H(2)O(2)); to estimate the
      activities of POX, CAT and glycolate oxidase (GO); and to study the diurnal
      variations in stomatal activity by scanning electron microscopy (SEM). From the
      results, plants grown in AH showed 55% higher H(2)O(2) production with about 30%
      increase in POX activity. Of the three substrates tested for POX activity
      (guaiacol, ascorbate and o-dianisidine), o-dianisidine was found as the preferred
      substrate of F. religiosa POX with about 7-fold more activity over its
      counterparts. Cytosolic POX activity showed 11-fold increase over cell wall bound
      POX. Similarly, CAT activity in specimens from AH showed about 2-fold increase
      during day time. The physiological interaction between CAT and its substrate
      H(2)O(2) in the plant was determined by quantifying H(2)O(2) and assaying the
      CAT, in which CAT showed 4-fold increases in activity, especially during night.
      F. religiosa has higher amount of H(2)O(2) deposition during night than day time,
      which was in correlation high CAT activity during night, coupled with scotoactive
      opening of stomata as shown by the SEM images. Moreover, GO did not show much
      habitat-dependent variation. In toto, F. religiosa grown in AH showed elevated
      production of ROS and their scavenging OSE, which is the direct evidence for
      drought stress and also giving an insight into its evolution and ecological
      niche.

PMID- 19162507
TI  - Prevention of chemotherapy-induced nausea and vomiting in elderly cancer
      patients.
AB  - There is a global and continuing increase in the population of elderly people.
      This is particularly true among patients with cancer including those receiving
      chemotherapy. There are no guidelines that in particular address prophylaxis of
      chemotherapy-induced nausea and vomiting (CINV) in the elderly. Elderly have a
      potential decreased risk of CINV due to the fact that they are often treated with
      less emetic chemotherapy and due to the fact that high age is protective. On the
      other hand, elderly have an increased risk of toxicity from antiemetics due to
      age-related decrease in organ function, use of poly-pharmacy with increased risk
      of drug-drug interactions and due to co-morbidity. Compliance needs to be
      carefully evaluated, particularly in patients with high risk of non-compliance,
      such as elderly with dementia and impaired vision.

PMID- 19162509
TI  - The role of obesity, biomechanical constitution of the pelvis and contact joint
      stress in progression of hip osteoarthritis.
AB  - OBJECTIVE: The aim of our study was to explore whether earlier hip arthroplasty
      for idiopathic osteoarthritis (OA) might be explained by enlarged contact stress
      in the hip joint, and to what amount can that be attributed to obesity and
      biomechanical constitution of the pelvis. METHOD: Fifty subjects were selected
      from a list of consecutive recipients of hip endoprosthesis due to idiopathic OA;
      standard pelvic radiographs made years prior to surgery were the main selection
      criteria. For 65 hips resultant hip force and peak contact hip stress normalized
      to the body weight (R/Wb and p(max)/Wb) were determined from the radiographs with
      the HIPSTRESS method. Body weight and body mass index (BMI) were obtained with an
      interview. Regression analysis was used to correlate parameters of obesity (body
      weight, BMI), biomechanical constitution of the pelvis (R/Wb, p(max)/Wb) and
      mechanical loading within the hip joint (R, p(max)) with age at hip arthroplasty.
      RESULTS: Younger age at hip arthroplasty was associated with higher body weight
      (P=0.009), higher peak contact hip stress normalized to the body weight -
      p(max)/Wb (P=0.019), higher resultant hip force -R (P=0.027) and larger peak
      contact hip stress - p(max) (P<0.001), but not with BMI (P=0.121) or R/Wb
      (P=0.614). CONCLUSION: Our results suggest that enlarged contact stress (p(max))
      plays an important role in rapid progression of hip OA with both obesity
      (increased body weight) and unfavorable biomechanical constitution of the pelvis
      (greater p(max)/Wb) contributing.

PMID- 19162510
TI  - Friend or foe? Role of peroxisome proliferator-activated receptor-gamma in human
      bladder cancer.
AB  - The peroxisome proliferator-activated receptor (PPAR) family is an important
      group of transcription factors that regulates immune surveillance, cell
      proliferation, fatty acid regulation, and angiogenesis--functions which have all
      been implicated in the pathogenesis of bladder cancer. One particular subtype,
      PPARgamma, is expressed at higher levels in bladder cancer specimens than in
      benign urothelium, and is an attractive molecular target for the development of
      novel treatment strategies for bladder cancer. In this review, we summarize the
      data available regarding relevance of PPARgamma in bladder cancer and discuss the
      potential value of PPAR-targeted treatment of bladder cancer.

PMID- 19162508
TI  - Road to the crossroads of life and death: linking sister chromatid cohesion and
      separation to aneuploidy, apoptosis and cancer.
AB  - Genomic instability, aberrant cell proliferation and defects in apoptotic cell
      death are critical issues in cancer. The two most prominent hallmarks of cancer
      cells are multiple mutations in key genes encoding proteins that regulate
      important cell-survival pathways, and marked restructuring or redistribution of
      the chromosomes (aneuploidy) indicative of genomic instability. Both these
      aspects have been suggested to cause cancer, though a causal role for chromosomal
      restructuring in tumorigenesis has not been experimentally fully substantiated.
      This review is aimed at understanding the mechanisms of cell cycle
      (proliferation) and programmed cell death (apoptosis) and chromosomal instability
      governed by cohesin and other aneuploidy promoters, which will provide new
      insights into the process of carcinogenesis and new avenues for targeted
      treatment.

PMID- 19162512
TI  - Testis cancer cells have a genetic determination for a high sensitivity to
      apoptosis inducing stimuli.
AB  - OBJECTIVE: The effect of cytotoxic therapy in testicular tumors (TGCT) has been
      shown to be mediated mainly by the induction of apoptosis. So far, it is not
      known which genes play a role for this inherent sensitivity to apoptosis inducing
      drugs. The aim of this study was to investigate the differential gene expression
      of apoptosis regulating genes in testicular tumors and in normal testis tissue
      using a quantitative method. As a premature S-phase entry was shown to induce
      apoptosis, genes controlling the G1/S-phase checkpoint were also investigated.
      MATERIAL AND METHODS: Gene expression levels of a representative subset of 19
      genes involved in apoptosis and cell cycle control were investigated in vivo in
      19 TGCTs using real-time quantitative PCR. Measurements were performed in tumor
      tissues of both tumor entities, seminomatous and non-seminomatous tumors (SGCT
      and NSGCT), and in corresponding biopsies from the unaffected site of the
      resected testis. RESULTS: There was an up-regulation of genes that play a role in
      facilitating apoptosis, such as FasL, TRAIL, and Bax in both tumor entities.
      Genes inhibiting apoptosis, such as Bcl-2 were predominantly down-regulated.
      Regarding cell cycle regulators, a gene expression profile was found that
      corresponds to a premature S phase entry and subsequent apoptosis induction.
      CONCLUSION: This study for the first time identified in vivo a panel of genes
      that give TGCT an inherent sensitivity to apoptotic stimuli after exposure to DNA
      damaging agents. Studies on these genes in therapy-refractory cancers should
      provide further insight into the mechanisms of chemotherapy resistance.
      Furthermore, these genes are promising targets for a future targeted therapy of
      testis cancer.

PMID- 19162513
TI  - Snail expression is an independent predictor of tumor recurrence in superficial
      bladder cancers.
AB  - BACKGROUND: Epithelial-mesenchymal transition (EMT) is known to play an important
      role in the development of tumor invasion and progression in tumors of epithelial
      origin. OBJECTIVES: Our aim was to investigate the role of Snail transcription
      repressor family members in human bladder pathogenesis. MATERIAL AND METHODS: We
      evaluated levels of Snail and Slug in 87 patients who received transurethral
      resection of a transitional cell carcinoma at our institution during the period
      from June 1999 until November 2003. Immunohistochemistry was performed on tissue
      microarrays, and expression correlated with pathological variables and clinical
      outcomes. Degree and intensity of Snail and Slug staining was quantified by
      immunohistochemistry. RESULTS: There was no apparent enrichment in strong vs.
      weak staining for either Snail (43.7% vs. 56.3%) or Slug (46% vs. 54%) in the
      superficial bladder tumors. Univariate analysis determined that tumor focality
      and Snail expression were significantly associated with tumor recurrence (P <
      0.05). Only for tumor focality did such a relationship exist when assessing tumor
      progression. Multivariate analysis using the Cox's proportional hazards model
      revealed similar results to that of the univariate analysis. Snail expression (P
      = 0.038) and tumor focality (P = 0.011) were independent and significant
      prognostic factors for tumor recurrence in all patients. However, only tumor
      focality was an independent predictor of tumor progression (P = 0.034).
      CONCLUSIONS: High expression of Snail in superficial bladder tumors is a strong
      predictor of tumor recurrence enhancing risk stratification and prognostication.

PMID- 19162511
TI  - The International Testicular Cancer Linkage Consortium: a clinicopathologic
      descriptive analysis of 461 familial malignant testicular germ cell tumor
      kindred.
AB  - OBJECTIVES: Familial aggregation of testicular germ cell tumor (TGCT) has been
      reported, but it is unclear if familial TGCT represents a unique entity with
      distinct clinicopathologic characteristics. Here we describe a collection of
      familial TGCT cases from an international consortium, in an effort to elucidate
      any clinical characteristics that are specific to this population. MATERIALS AND
      METHODS: Families with >or=2 cases of TGCT enrolled at 18 of the sites
      participating in the International Testicular Cancer Linkage Consortium were
      included. We analyzed clinicopathologic characteristics of 985 cases from 461
      families. RESULTS: A majority (88.5%) of families had only 2 cases of TGCT. Men
      with seminoma (50% of cases) had an older mean age at diagnosis than nonseminoma
      cases (P = 0.001). Among individuals with a history of cryptorchidism, TGCT was
      more likely to occur in the ipsilateral testis (kappa = 0.65). Cousin pairs
      appeared to represent a unique group, with younger age at diagnosis and a higher
      prevalence of cryptorchidism than other families. CONCLUSIONS: Clinicopathologic
      characteristics in these familial TGCT cases were similar to those generally
      described for nonfamilial cases. However, we observed a unique presentation of
      familial TGCT among cousin pairs. Additional studies are needed to further
      explore this observation.

PMID- 19162514
TI  - Enhanced GSTP1 expression in transitional cell carcinoma of urinary bladder is
      associated with altered apoptotic pathways.
AB  - OBJECTIVES: Glutathione S-transferase P1 (GSTP1) provides an important link
      between activity of regulatory stress kinases and apoptotic pathways. It can be
      hypothesized that up-regulated GSTP1, in TCC, might enhance apoptosis inhibition.
      We aimed to establish whether relationship between GSTP1 expression and executive
      (pro-caspase 3, cleaved caspase 3) and regulatory (Bcl-2) apoptotic pathways in
      TCC exists. MATERIALS AND METHODS: Samples were obtained from 84 TCC patients (41
      consecutive patient with muscle noninvasive and 43 consecutive patients with
      muscle invasive TCC tumors), who underwent surgery at the Institute of Urology
      and Nephrology, Clinical Centre of Serbia, during 2006 and 2007. Expression of
      GSTP1, pro-caspase 3 (CPP32), and Bcl-2, as well as cleaved caspase-3 labeling
      index (LI) were determined by immunocytochemistry. Levels of expression were
      correlated with tumor stage, grade, and invasiveness. RESULTS: GSTP1 protein
      expression was demonstrated in all tumor samples examined. According to GSTP1
      status, all tumors were divided into groups with low, moderate, or high GSTP1
      status. Expression of CPP32 and cleaved caspase 3 was positive in 80% of TCC
      patients. Their levels differed significantly between groups with various GSTP1
      expression (P < 0.05), with the lowest CPP32 expression and cleaved caspase 3 LI
      in tumors with high GSTP1 status. Moreover, significant negative correlation was
      found between GSTP1 level and cleaved caspase 3 LI (r = -0.459, P = 0.041). The
      positive rate of Bcl-2 protein expression was 48%. Most of the Bcl-2 positive
      patients exhibited at the same time high GSTP1 positivity (P = 0.078).
      Significant association with tumor grade and stage was found for all examined
      parameters except for CPP32 regarding tumor grade. CONCLUSIONS: Based on results
      obtained, we conclude that enhanced GSTP1 expression in TCC of urinary bladder is
      associated with altered apoptotic pathways. Molecular interplay between GSTP1 and
      members of apoptotic cascade might, at least partially, play a role in
      development of invasive characteristics of TCC.

PMID- 19162515
TI  - Combined intermittent pneumatic leg compression and pharmacological prophylaxis
      for prevention of venous thrombo-embolism in high-risk patients.
AB  - BACKGROUND: It has been suggested that combined modalities (methods of treatment)
      are more effective than single modalities in preventing venous thrombo-embolism
      (defined as deep vein thrombosis and pulmonary embolism, or both) in high-risk
      patients. OBJECTIVES: To assess the efficacy of intermittent pneumatic leg
      compression combined with pharmacological prophylaxis versus single modalities in
      preventing venous thrombo-embolism in high-risk patients. SEARCH STRATEGY: The
      Cochrane Peripheral Vascular Diseases (PVD) Group searched the reference lists of
      their Specialised Register (last searched 17 July 2007) and the Cochrane Central
      Register of Controlled Trials (CENTRAL) (last searched The Cochrane Library 2008,
      issue 3) for relevant articles to identify additional trials. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) of
      combined intermittent pneumatic leg compression and pharmacological interventions
      used to prevent venous thrombo-embolism in high-risk patients. DATA COLLECTION
      AND ANALYSIS: Data extraction was undertaken independently by two review authors
      using data extraction sheets.

PMID- 19162516
TI  - Urgent carotid surgery in patients with crescendo transient ischaemic attacks and
      stroke-in-evolution: a systematic review.
AB  - OBJECTIVE: To document outcomes after urgent carotid surgery in patients with
      crescendo transient ischaemic attacks (CTIAs) and stroke-in-evolution (SIE).
      METHODS: A systematic review of the English-language literature using the MEDLINE
      and EMBASE databases "was undertaken from January 1984 through December 2007".
      Studies reporting the data after surgery for CTIAs and SIE were identified and
      stroke, stroke/death and stroke/death/major cardiac event rates calculated. The
      studies were divided into those reporting on CTIAs (group I) and those reporting
      on SIE (group II). RESULTS: From the databases, 34 relevant series (915 patients)
      were retrieved. After excluding those reports on CTIAs, SIE and other 'urgent'
      indications combined together and from which separate data could not be
      extracted, a total of 12 series with 176 patients reporting on CTIAs (group I)
      and 16 series with 114 patients reporting on SIE (group II) met the inclusion
      criteria. All the identified studies were case series of low methodological
      quality suffering from selection bias. Peri-operative stroke, stroke/death and
      stroke/death/major cardiac event rates were 6.5% (95% confidence interval (CI):
      3.4-10.4), 9.0% (95% CI: 4.3-15.1) and 10.9% (95% CI: 5.5-17.9), respectively, in
      group I; and 16.9% (95% CI: 9.2-26.2), 20.0% (95% CI: 12.5-28.6) and 20.8% (95%
      CI: 13.2-29.6), respectively, in group II. CONCLUSIONS: The combined risk of
      neurological and cardiac complications following urgent carotid surgery for
      unstable neurological symptoms, such as CTIAs and SIE, is higher than that
      anticipated after elective surgery for stable symptoms.

PMID- 19162517
TI  - Generation of laser-polarized xenon using fiber-coupled laser-diode arrays
      narrowed with integrated volume holographic gratings.
AB  - Volume holographic gratings (VHGs) can be exploited to narrow the spectral output
      of high-power laser-diode arrays (LDAs) by nearly an order of magnitude,
      permitting more efficient generation of laser-polarized noble gases for various
      applications. A approximately 3-fold improvement in (129)Xe nuclear spin
      polarization, P(Xe), (compared to a conventional LDA) was achieved with the VHG
      LDA's center wavelength tuned to a wing of the Rb D(1) line. Additionally, an
      anomalous dependence of P(Xe) on the xenon density within the OP cell is reported
      including high P(Xe) values (>10%) at high xenon partial pressures (approximately
      1000 torr).

PMID- 19162518
TI  - Dynamic Nuclear Polarization of [1-13C]pyruvic acid at 4.6 tesla.
AB  - Dynamic Nuclear Polarization (DNP) of the (13)C nucleus has been investigated for
      [1-(13)C]pyruvic acid, doped with the trityl radical OX063Me, at 4.64 T and
      1.15K. The dependence of the polarization on microwave frequency, radical
      concentration and electron saturation was studied. For optimized conditions, a
      (13)C polarization equal to 64+/-5% was obtained, an increase by more than a
      factor of two compared with earlier results at 3.35 T of the same system. It was
      furthermore observed that the addition of gadolinium, which resulted in a twofold
      polarization increase at 3.35 T, only resulted in a minor improvement at 4.64 T.
      The dependence of the electron saturation on microwave frequency and microwave
      power was quantified by first moment measurements which were obtained by nucleus
      electron double resonance (NEDOR) experiments. Complete electron saturation was
      observed for a microwave frequency close to the centre frequency of the ESR line,
      and by using maximum power of the microwave source. The DNP build-up time at 4.64
      T (approximately 3000 s) was prolonged by approximately a factor three over the
      build-up time at 3.35 T (approximately 1200 s). However, after approximately 20
      min of microwave irradiation the polarization at 4.64 T exceeded the polarization
      at 3.35 T.

PMID- 19162519
TI  - [Adjuvant irradiation in breast cancer patients with ATM gene heterozygous
      mutations: special focus on clinical efficacy/toxicity].
AB  - Dysfunction of the ataxia telangiectasia mutated (ATM) gene has been related to
      defective cell cycle control and genomic instability due to the impaired repair
      of DNA double strand breaks. Although increased radiosensitivity in ATM
      heterozygous patients has been suggested in preclinical data, clinical
      implication of ATM variant remains debated. Despite frequent in vitro
      hypersensitivity in patients with severe radiation-induced delayed toxicity,
      heterozygoty for ATM gene does not represent the major cause of unexpected
      complications after radiation therapy. This might be partially due to potential
      coexistence of alterations in additional genes that would play a role in
      development of late radiation-induced adverse response. Although several data
      suggest that some ATM polymorphisms would increase grade 3 subcutaneous fibrosis
      at lower doses compared with patients who did not possess these genetic
      alterations, the relationship between the presence of ATM mutations or sequence
      variants and radiation-induced toxicity remains controversial in part because of
      their biological and functional significance. Considering the lack of prospective
      data, patients with ATM mutation should be considered as candidates for both dose
      volume and dose reduction clinical trials.

PMID- 19162520
TI  - Nerve transfers in brachial plexus palsies.
AB  - It has been many years now since the introduction of nerve transfers for repair
      of traumatic brachial plexus lesions and more recently, we have seen its
      application in the field of obstetric brachial plexus palsy. These nerve
      transfers do not represent an alternative to anatomical repair by means of nerve
      grafting, but represent an additional possibility to increase the reconstructive
      options and improve the final results. This pushes the surgeon to decide: which
      function is to be restored by nerve grafting, which one by nerve transfer? What
      is the more reliable procedure? Does the age of the patient, the delay after the
      accident, or the type of accident influence this choice? If we add in the
      possibilities of palliative treatment, one can state that many therapeutic
      options are available today for brachial plexus reconstruction, and that no real
      consensus does exist. But some tendencies, some trends are apparent.

PMID- 19162521
TI  - Sonochemical decay of C.I. Acid Orange 8: effects of CCl4 and t-butyl alcohol.
AB  - Sonochemical degradation of aryl-azo-naphthol dyes represented by C.I. Acid
      Orange 8 was investigated at 300 kHz to assess the operational parameters and the
      impacts of rate enhancers (CCl(4)) and rate inhibitors (t-butyl alcohol). It was
      found that the degradation of the dye was accelerated with increased
      concentrations of CCl(4) via the accumulation of reactive chlorine species and
      the hindrance of OH radical combination reactions with atomic hydrogen. The
      addition of t-butyl alcohol at all test concentrations inhibited the degradation
      of the dye regardless of the quantity of OH radicals (or H(2)O(2)) in solution.
      The inhibition was explained by the competition of the dye and t-butyl alcohol at
      the gas-liquid interface. Finally, the rate of dye degradation in the presence of
      both reagents at their effective concentrations was found to be considerably
      slower than that with CCl(4), showing that the formation of reactive chlorine
      species was remarkably suppressed by the rapid reaction of t-butyl alcohol at the
      gas-liquid interface.

PMID- 19162522
TI  - Frequency of heterozygous Parkin mutations in healthy subjects: need for careful
      prospective follow-up examination of mutation carriers.
AB  - The role of single heterozygous mutations in the putatively recessive Parkin gene
      in Parkinson disease (PD) is a vividly debated issue, partly caused by the
      largely unknown frequency of these mutations in healthy individuals. We
      investigated mutations in all 12 Parkin exons in 356 controls from two European
      populations including individuals from South Tyrol and Germany. None of the
      controls carried a homozygous or compound heterozygous mutation. Seventeen
      carriers of rare heterozygous alterations were detected, of which 13 (13/356;
      3.7%) are considered to alter protein structure including four different gene
      dosage alterations, four missense mutations, and two frameshift mutations. Two of
      the mutations occurred recurrently in the South Tyrolean population. There was no
      obvious difference in the mutation frequency between the two populations. One of
      the presumably healthy mutation carrier was available for re-examination at the
      age of 67 years. He presented with mild signs of parkinsonism but not fulfilling
      diagnostic criteria for definite PD. To elucidate the role of heterozygosity is
      important for genetic testing and counseling of mutation carriers. A detailed
      clinical prospective and follow-up examination of mutation carriers is required
      for a better understanding of the role of heterozygous Parkin mutations.

PMID- 19162523
TI  - The effects of refurbishment on residents' quality of life and wellbeing in two
      Swedish residential care facilities.
AB  - This study was conducted to follow a refurbishment aimed at enhancing the
      supportiveness of the physical environment in two Swedish residential care
      facilities. Significant differences between intervention and equivalent reference
      groups were found for quality of life (p=0.007) and wellbeing (p=0.02, 0.01)
      indicating a deterioration for the intervention group. These results suggest that
      residential care facilities residents are more frail and sensitive to change than
      has been assumed. This needs to be considered when facilities accommodating the
      elderly need refurbishment. It also indicates that interior design features alone
      have little importance for the care climate in nursing homes.

PMID- 19162524
TI  - Green plants that feed on fungi: facts and questions about mixotrophy.
AB  - Several green, photosynthetic plants in orchids and Ericaceae were recently found
      to recover carbon from the mycorrhizal fungi associated with their roots, a dual
      nutritional capability called mixotrophy. The physiological and cellular
      processes allowing carbon gain from the fungus are not well understood. We
      believe that this phenomenon is overlooked and propose several land plant
      families and ecosystems that should be investigated for possible mixotrophy. We
      speculate that mixotrophy allowed, in some lineages, the evolution of
      heterotrophic plants, that is, non-photosynthetic plants that obtain their carbon
      from organic compounds. Moreover, the amount of carbon gained from the fungus
      varies from one site to another in mixotrophs. Drawing a parallel with mixotrophy
      in planktonic algae, we propose some hypotheses that could account for this.

PMID- 19162525
TI  - N-glycan production in the endoplasmic reticulum of plants.
AB  - N-glycosylation is a complex process that encompasses the biosynthesis and
      modification of sugar moieties in the endoplasmic reticulum (ER) and Golgi. The
      ER-localized steps of N-glycan production in plants have received relatively
      little attention, despite their emerging roles in stress responses. Here, we
      integrate information on the molecular components underlying the three stages of
      N-glycan production: lipid-linked oligosaccharide synthesis, co-translational
      oligosaccharyl-transfer and quality control of the folded glycoprotein in the ER.
      The relative importance of each step for N-glycosylation and plant performance is
      evaluated on the basis of studies with inhibitors and mutant phenotypes. Finally,
      we highlight the increasing evidence for crosstalk between N-glycan production
      and defence responses in plants and discuss the practical implications for
      pathogen resistance.

PMID- 19162526
TI  - Cell-type-specific differentiation of chloroplasts in C4 plants.
AB  - In leaves of C4 grasses such as maize, photosynthetic activities are partitioned
      between bundle-sheath and mesophyll cells, leading to increased photosynthetic
      yield, particularly under stress conditions. As we discuss here, recent
      comparative chloroplast proteome analyses in maize have shown specific adaptation
      to C4-cell-specific differentiation of the photosynthetic apparatus, primary and
      secondary metabolism and metabolite transporters, as well as the chloroplast
      protein homeostasis machinery. Furthermore, a novel bundle-sheath-enriched 1000
      kDa NADPH dehydrogenase 'supercomplex' has been identified, and we discuss its
      possible role in inorganic carbon concentration. These breakthroughs provide new
      opportunities to further unravel C4 pathways and to increase crop productivity
      through metabolic engineering of C4 pathways into C3 plants, such as rice.

PMID- 19162527
TI  - Protein tyrosine phosphorylation in plants: More abundant than expected?
AB  - Protein phosphorylation in eukaryotes predominantly occurs on serine (Ser) and
      threonine (Thr) residues, whereas phosphorylation on tyrosine (Tyr) residues is
      less abundant. Plants lack classic Tyr kinases, such as the epidermal growth
      factor receptor, that govern Tyr phosphorylation in animals. A long-standing
      debate questions whether plants have any Tyr-specific kinases and, although
      several protein kinases with both Ser/Thr and Tyr specificities exist, data
      supporting the existence of other such kinases are scarce. As we discuss here,
      mass-spectrometry-based analyses now indicate that Tyr phosphorylation is as
      extensive in plants as it is in animals. However, careful inspection of available
      data indicates that these promising mass spectrometry studies have to be
      interpreted with caution before current ideas on Tyr phosphorylation in plants
      are revised.

PMID- 19162528
TI  - Jasmonate-inducible gene: What does it mean?
AB  - The diverse functions of jasmonates (JAs) in plant cells are reflected by the
      extensive reprogramming of gene expression after JA perception. Here, we review
      the transcriptome signatures associated with JA signalling in Arabidopsis
      thaliana and other plant species. Transcript profiling studies clearly highlight
      the renowned capacity of JAs to elicit evolutionarily distant metabolic pathways
      across the plant kingdom. However, JA-related transcriptomes show limited overlap
      and, for most cellular processes, the context in which the JA signal is perceived
      is crucial in shaping the response. This emphasizes that JA signal transduction
      is integrated into an elaborate signalling network.

PMID- 19162529
TI  - A 2D/3D correspondence building method for reconstruction of a patient-specific
      3D bone surface model using point distribution models and calibrated X-ray
      images.
AB  - Constructing a 3D bone surface model from a limited number of calibrated 2D X-ray
      images (e.g. 2) and a 3D point distribution model is a challenging task,
      especially, when we would like to construct a patient-specific surface model of a
      bone with pathology. One of the key steps for such a 2D/3D reconstruction is to
      establish correspondences between the 2D images and the 3D model. This paper
      presents a 2D/3D correspondence building method based on a non-rigid 2D point
      matching process, which iteratively uses a symmetric injective nearest-neighbor
      mapping operator and 2D thin-plate splines based deformations to find a fraction
      of best matched 2D point pairs between features extracted from the X-ray images
      and those extracted from the 3D model. The estimated point pairs are then used to
      set up a set of 3D point pairs such that we turn a 2D/3D reconstruction problem
      to a 3D/3D one, whose solutions are well studied. Incorporating this 2D/3D
      correspondence building method, a 2D/3D reconstruction scheme combining a
      statistical instantiation with a regularized shape deformation has been
      developed. Comprehensive experiments on clinical datasets and on images of
      cadaveric femurs with both non-pathologic and pathologic cases are designed and
      conducted to evaluate the performance of the 2D/3D correspondence building method
      as well as that of the 2D/3D reconstruction scheme. Quantitative and qualitative
      evaluation results are given, which demonstrate the validity of the present
      method and scheme.

PMID- 19162531
TI  - Genetical metabolomics: closing in on phenotypes.
AB  - One of the long-standing goals in plant biology has been to link genotypic
      variation to natural variation in plant development and adaptive traits. From
      recent studies it has become clear that a complex interacting network is
      underlying phenotypic diversity. A major role in this regulatory mechanism is
      assigned to the metabolism since plants are extremely rich and variable in
      metabolic content profiles. Technological advances in detecting and quantifying
      biochemical content as well as novel experimental approaches have accelerated
      data generation and increased our understanding of regulatory mechanisms in plant
      biology. It is now clear that modern plant sciences can benefit enormously from
      integrated multidisciplinary approaches.

PMID- 19162532
TI  - Translating Medicago truncatula genomics to crop legumes.
AB  - Genomic resources developed in the model legume, Medicago truncatula, have the
      potential to accelerate practical advances in crop legumes. M. truncatula is
      closely related to many economically important legumes, frequently displaying
      genome-scale synteny. Translating genome data from M. truncatula should be highly
      effective in marker development, gene discovery, and positional cloning in crop
      legumes. The M. truncatula genome sequence also provides valuable insights about
      gene families of practical importance, especially those that are legume-specific.
      The M. truncatula genome sequence should also simplify the assembly of next
      generation sequence data in closely related taxa, especially alfalfa. Genomic
      resources, such as whole-genome arrays, make it possible to pursue detailed
      questions about gene expression in both M. truncatula and related crop species,
      while tagged mutant populations simplify the process of determining gene
      function.

PMID- 19162530
TI  - Mechanisms of resistance to FLT3 inhibitors.
AB  - The success of the small molecule tyrosine kinase receptor inhibitor (TKI)
      imatinib mesylate (Gleevec) in the treatment of chronic myeloid leukemia (CML)
      constitutes an eminent paradigm shift advocating the rational design of cancer
      therapeutics specifically targeting the transformation events that drive
      tumorigenicity. In acute myeloid leukemias (AMLs), the most frequent identified
      transforming events are activating mutations in the FLT3 receptor tyrosine kinase
      that constitutively activate survival and proliferation pathways. FLT3 TKIs that
      are in various phases of clinical trials are showing some initial promise.
      However, primary and secondary acquired resistance stands to severely compromise
      long-term and durable efficacy of these inhibitors as a therapeutic strategy.
      Here, we discuss the mechanisms of resistance to FLT3 inhibitors and possible
      strategies to overcome resistance through closer examination of the events of
      leukemogenesis and design of combination therapy.

PMID- 19162533
TI  - The type VI secretion system: translocation of effectors and effector-domains.
AB  - A number of prominent Gram-negative bacteria use the type VI secretion system
      (T6SS) to transport proteins across the bacterial envelope. Rapid progress is
      being made in elucidating the structural components of the T6SS apparatus, and a
      few effectors have been reported to pass through it. However, this is not the
      complete story: a family of T6SS proteins, the VgrGs, share structural features
      with the cell-puncturing device of the T4 bacteriophage, and may be used in a
      similar fashion by bacteria to puncture host cell membranes and insert the T6SS
      apparatus into the host cytosol. Interestingly, a number of VgrGs contain C
      terminal extensions with effector-domains. Thus, the T6SS may translocate soluble
      effectors, as well as VgrG effector-domains.

PMID- 19162534
TI  - Electronic, Raman and FT-IR spectral investigations of the charge transfer
      interactions between ketoconazole and povidone drugs with iodine.
AB  - The interaction between ketoconazole and povidone drugs with iodine was found to
      proceed through initial formation of a charge transfer (CT) complex as an
      intermediate. The stoichiometry of the complex was found to be 1:1 in the case of
      povidone-iodine system and 1:2 in the case of ketoconazole-iodine system and the
      same was confirmed by thermal (TGA/DSC) studies. The formation of I(3)(-) species
      was confirmed by electronic and laser Raman spectra. The three peaks appeared in
      Raman spectra, of the isolated adducts corresponds to nu(as)(I-I), nu(s)(I-I) and
      delta(I(3)(-)), confirmed the presence of asymmetric I(3)(-) ion. The rate of the
      interaction has been measured as a function of time and solvent. The pseudo-first
      order rate constants at various temperatures for the interactions were measured
      and the activation parameters (DeltaG(#), DeltaS(#) and DeltaH(#)) were computed.
      Based on the spectral and spectrokinetic evidences a mechanism involving the
      formation of a polar intermediate and its conversion to the final product has
      been proposed and discussed.

PMID- 19162535
TI  - Synthesis, spectral, thermal and anti-fungal studies of organotin(IV)
      thiohydrazone complexes.
AB  - The reaction of tribenzyltin(IV) chloride and di(para-chlorobenzyl)tin(IV)
      dichloride with thiohydrazones derived by condensation of 2-phenylethyl N
      thiohydrazide with benzaldehyde, salicaldehyde, p-methylacetophenone and
      cinnamaldehyde have been investigated in 1:1 molar ratio. These ligands act as
      neutral, bidentate species and coordinate to the central tin (IV) atom through
      the thiosulphur and azomethine nitrogen. The newly synthesized complexes have
      been characterized by elemental analysis and molecular weight determination. The
      mode of bonding of the complexes has been suggested on the basis of infrared,
      electronic and (1)H NMR spectroscopy, and probable structures have been assigned
      to these complexes. Phenomenological and kinetic parameters have been calculated
      using thermogravimetric (TG) and differential thermal analytical (DTA) curves and
      their variations have been correlated with some structural parameters of the
      complexes. The ligands and their tin(IV) complexes have been screened in vitro
      for their fungicidal activity against Rhizoctonia solanii and Sclerotium rolfsii
      and found to be quite active in this respect.

PMID- 19162536
TI  - Complexation of anthracene with folic acid studied by FTIR and UV spectroscopies.
AB  - Toxicity and transformation process of polycyclic aromatic hydrocarbons (PAHs) is
      strongly depended on the interaction between PAHs and the coexisting compounds.
      Complexation between folic acid (FA) and a typical PAH, anthracene, was
      investigated using FTIR and UV spectra. Appearance of a new IR band at 2362cm(-1)
      demonstrates that NH(2)-CN(1)- moiety on pterin (PT) ring in FA is protonated
      when anthracene is introduced. The shift of the characteristic IR band of the PT
      ring and the emergence of two charge transfer bands at 254nm and 246nm in UV
      difference spectra show the presence of pi-pi complexation between folic acid and
      anthracene. These experiments confirm that anthracene could combine with the
      pterin ring of folic acid through pi-pi donor-acceptor interaction (EDA) and
      induce the protonation process in FA upon strengthening electron accepting
      ability of PT ring.

PMID- 19162537
TI  - Synthesis, characterization and fluorescence properties of Eu(III) and Tb(III)
      complexes with novel mono-substituted beta-diketone ligands and 1,10
      phenanthroline.
AB  - Two novel pyridine-2,6-dicarboxylic acid derivatives of mono-beta-diketone,
      methyl 6-benzoylacetyl-2-pyridinecarboxylate (MBAP) and 6-benzoylacetyl-2
      pyridinecarboxylic acid (BAPA) and their Eu(III) and Tb(III) complexes were
      synthesized and characterized by elemental analysis, FT-IR, (1)H NMR and TG-DTG.
      Moreover, their Eu(III) and Tb(III) complexes using 1,10-phenanthroline as a
      secondary ligand were prepared and characterized. The luminescence properties of
      these complexes in solid state were investigated in detail. The results suggested
      that Tb(III) complexes exhibit more efficient luminescence than Eu(III)
      complexes, the fluorescence intensity of Ln(III) complexes with BAPA is about
      twice as strong as that of Ln(III) complexes with MBAP, the fluorescence of mono
      beta-diketone complexes using 1,10-phenanthroline as a secondary ligand was
      prominently higher than that of complexes without adding 1,10-phenanthroline, and
      the ligand BAPA is an excellent sensitizer to Eu(III) and Tb(III) ion.

PMID- 19162538
TI  - Architecture of a wireless Personal Assistant for telemedical diabetes care.
AB  - PURPOSE: Advanced information technologies joined to the increasing use of
      continuous medical devices for monitoring and treatment, have made possible the
      definition of a new telemedical diabetes care scenario based on a hand-held
      Personal Assistant (PA). This paper describes the architecture, functionality and
      implementation of the PA, which communicates different medical devices in a
      personal wireless network. DESCRIPTION OF THE SYSTEM: The PA is a mobile system
      for patients with diabetes connected to a telemedical center. The software design
      follows a modular approach to make the integration of medical devices or new
      functionalities independent from the rest of its components. Physicians can
      remotely control medical devices from the telemedicine server through the
      integration of the Common Object Request Broker Architecture (CORBA) and mobile
      GPRS communications. Data about PA modules' usage and patients' behavior
      evaluation come from a pervasive tracing system implemented into the PA. RESULTS
      AND DISCUSSION: The PA architecture has been technically validated with
      commercially available medical devices during a clinical experiment for
      ambulatory monitoring and expert feedback through telemedicine. The clinical
      experiment has allowed defining patients' patterns of usage and preferred
      scenarios and it has proved the Personal Assistant's feasibility. The patients
      showed high acceptability and interest in the system as recorded in the usability
      and utility questionnaires. Future work will be devoted to the validation of the
      system with automatic control strategies from the telemedical center as well as
      with closed-loop control algorithms.

PMID- 19162539
TI  - Natural hybrids in the marine diatom Pseudo-nitzschia pungens
      (Bacillariophyceae): genetic and morphological evidence.
AB  - Hybridization between genetically distinguishable taxa provides opportunities for
      investigating speciation. While hybridization is a common phenomenon in various
      macro-organisms, natural hybridization among micro-eukaryotes is barely studied.
      Here we used a nuclear and a chloroplast molecular marker and morphology to
      demonstrate the presence of natural hybrids between two genetically and
      morphologically distinct varieties of the marine planktonic diatom Pseudo
      nitzschia pungens (vars. pungens and cingulata) in a contact zone in the
      northeast Pacific. Cloning and sequencing of the rDNA internal transcribed spacer
      region revealed strains containing ribotypes from both varieties, indicating
      hybridization. Both varieties were found to also have different chloroplast
      encoded rbcL sequences. Hybrid strains were either hetero- or homoplastidial, as
      demonstrated by denaturing gradient gel electrophoresis, which is in accordance
      with expectations based on the mode of chloroplast inheritance in Pseudo
      nitzschia. While most hybrids are probably first generation, there are also
      indications for further hybridization. Morphologically, the hybrids resembled
      var. pungens for most characters rather than having an intermediate morphology.
      Further research should focus on the hybridization frequency, by assessing the
      spatial and temporal extent of the contact zone, and hybrid fitness, to determine
      the amount of gene flow between the two varieties and its evolutionary
      consequences.

PMID- 19162540
TI  - Genetic diversity patterns in five protist species occurring in lakes.
AB  - Little is known about the extent of the genetic diversity and its structuring
      patterns in protist species living in lakes. Here, we have investigated the
      genetic diversity patterns within five dinoflagellate species (Peridinium
      aciculiferum, Peridinium cinctum, Peridiniopsis borgei, Polarella glacialis,
      Scrippsiella aff. hangoei) that are present in lakes and sometimes, in marine
      habitats located in polar and temperate regions. A total of 68 clonal strains
      were investigated using Amplified Fragment Length Polymorphism (AFLP), a
      sensitive genetic fingerprinting technique. All used strains within each species
      had identical ITS nuclear ribosomal DNA sequences, a characteristic that
      indicates that they likely belong to the same species. We found a wide
      variability in the genetic diversity among species (between 20% and 90% of
      polymorphic loci; Nei's gene diversity between 0.08 and 0.37). In some cases, our
      analyses suggested the presence of different genetically homogeneous subgroups
      (genetic populations) within the same water body. Thus, it appears that different
      genetic populations can coexist within the same lake despite the likely
      occurrence of recombination that tends to homogenize the gene pool. Overall, our
      results indicated that a large number of dinoflagellate genotypes are present in
      lake populations, instead of a few dominating ones. In addition, our study shows
      that protists with identical ITS sequences can harbor considerable amounts of
      genetic diversity.

PMID- 19162541
TI  - Meeting Report IFoLeish-2008: current status and future challenges in Leishmania
      Research and Leishmaniasis.

PMID- 19162542
TI  - Localization of perialgal vacuoles beneath the host cell surface is not a
      prerequisite phenomenon for protection from the host's lysosomal fusion in the
      ciliate Paramecium bursaria.
AB  - In a ciliate Paramecium bursaria cell, each symbiotic 3-4-mum-diameter Chlorella
      cell is enclosed within a perialgal vacuole membrane. It localizes near
      trichocysts beneath the host cell surface. Gomori's staining of this surface
      shows that it is an acid phosphatase activity-negative area to 5-10mum depth.
      Trichocysts were removed by treatment with 1mg/ml lysozyme to elucidate whether
      algal protection from the host lysosomal fusion is controlled by localization of
      the perialgal vacuole membrane to the acid phosphatase activity-negative area or
      by the capability of the perialgal vacuole membrane to give protection from
      lysosomal fusion. The trichocyst-free cell reduced the acid phosphatase activity
      negative area to less than 3mum depth at the dorsal surface. However, even though
      a part of the algal cell had been exposed in the acid phosphatase activity
      positive area, the algae were able to attach beneath the host surface and to
      protect it from lysosomal fusion. Results of this study show that the perialgal
      vacuole membrane can give protection from host lysosomal fusion, and that the
      membrane does not require trichocysts for intracellular localization.

PMID- 19162543
TI  - Predictors of successful early extubation following congenital cardiac surgery in
      neonates and infants.
AB  - BACKGROUND: There is a paucity of literature discussing the predictive likelihood
      of successfully extubating neonates and infants in the operating room immediately
      following congenital cardiac surgery. Given the unknown consequences of
      anaesthetics on neurodevelopmental outcomes, minimising the exposure of this
      population to such agents may have long-term benefits. METHODS: Retrospective
      chart review of 391 patients less than 1 year of age. RESULTS: The probability of
      successfully extubating these patients was based on quantifiable, objective
      criteria. The relevant variables include age, weight, bypass time, lactate level
      and specific congenital anomaly. CONCLUSIONS: The practice of immediate
      extubation of infants and neonates is achievable, safe and predicted based on
      specific patient variables. This practice will minimise the anaesthetic exposure
      of these especially young patients who may be at risk for long-term consequences
      related to anaesthetic exposure.

PMID- 19162545
TI  - Responses to stress: from the periphery to the brain.

PMID- 19162544
TI  - Dissecting components of reward: 'liking', 'wanting', and learning.
AB  - In recent years significant progress has been made delineating the psychological
      components of reward and their underlying neural mechanisms. Here we briefly
      highlight findings on three dissociable psychological components of reward:
      'liking' (hedonic impact), 'wanting' (incentive salience), and learning
      (predictive associations and cognitions). A better understanding of the
      components of reward, and their neurobiological substrates, may help in devising
      improved treatments for disorders of mood and motivation, ranging from depression
      to eating disorders, drug addiction, and related compulsive pursuits of rewards.

PMID- 19162546
TI  - Induced pluripotent stem cells: current progress and potential for regenerative
      medicine.
AB  - Lineage-restricted cells can be reprogrammed to a pluripotent state through
      overexpression of defined transcription factors. Here, we summarize recent
      progress in the direct reprogramming field and discuss data comparing embryonic
      stem (ES) and induced pluripotent stem (iPS) cells. Results from many independent
      groups suggest that mouse and human iPS cells, once established, generally
      exhibit a normal karyotype, are transcriptionally and epigenetically similar to
      ES cells and maintain the potential to differentiate into derivatives of all germ
      layers. Recent developments provide optimism that safe, viral-free human iPS
      cells could be derived routinely in the near future. An important next step will
      be to identify ways of assessing which iPS cell lines are sufficiently
      reprogrammed and safe to use for therapeutic applications. The approach of
      generating patient-specific pluripotent cells will undoubtedly transform
      regenerative medicine in many ways.

PMID- 19162547
TI  - C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical
      progress.
AB  - C1 inhibitor (C1-INH, also known as SERPING1) can be deficient in plasma as a
      result of genetic or acquired conditions, and this causes an episodic, local
      increase in vascular permeability in the subcutaneous and submucosal layers,
      identified as angioedema (hereditary or acquired). Bradykinin, the mediator of
      the increase in vascular permeability, is released on inappropriate activation of
      the contact system, which is controlled by C1 inhibitor. Therapy aims to reverse
      or prevent angioedema. Advances in understanding the complex effects of C1-INH
      deficiency at the molecular level have led to new molecular-targeted approaches.
      Three new treatments, an inhibitor of kallikrein to prevent bradykinin release,
      an antagonist of the bradykinin receptor to prevent its action and a recombinant
      human C1-INH produced in transgenic animals, are under clinical evaluation
      currently. Here, we review the molecular mechanisms underlying angioedema due to
      C1-inhibitor deficiency and clinical progress using molecular-targeted
      interventions.

PMID- 19162548
TI  - TGF-beta and kynurenines as the key to infectious tolerance.
AB  - The maintenance of self-tolerance is an integral part of the immune surveillance
      process, in which cytokines act as master regulators of a complex network
      involving multiple cell types. On such cytokines, transforming growth factor-beta
      (TGF-beta) exerts a suppressive control over immune reactivity, which so far
      appears to be mostly confined to the T-cell compartment. Recently, dendritic
      cells (DCs) have been found to be both an early source and a target of TGF-beta
      actions. In these cells, autocrine, paracrine and T-cell-derived TGF-beta
      activates the tolerogenic pathway of tryptophan catabolism - mediated by
      indoleamine 2,3-dioxygenase (IDO) - resulting in a burst of regulatory
      kynurenines that contribute to establishing a state of 'infectious tolerance'.
      Current molecular insights suggest a synergistic potential for TGF-beta and IDO
      in physiologically or therapeutically opposing human pathologies sustained by
      over-reacting immune responses.

PMID- 19162549
TI  - Heme oxygenase-1: from biology to therapeutic potential.
AB  - Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that catabolizes free heme
      into carbon monoxide, iron (which induces the expression of heavy-chain ferritin,
      an iron-sequestering protein) and biliverdin (which is converted to bilirubin by
      biliverdin reductase). Over the past few years it has become apparent that these
      'arms' of the HO-1 system can act protectively in a variety of experimental
      models of disease; there is also evidence that HO-1 and bilirubin have protective
      actions in humans. Here, we present a model for the beneficial actions of the
      products of heme degradation, and we discuss the potential clinical applications
      of enhancing the HO-1 system.

PMID- 19162550
TI  - What are microarrays teaching us about sleep?
AB  - Many fundamental questions about sleep remain unanswered. The presence of sleep
      across phyla suggests that it must serve a basic cellular and/or molecular
      function. Microarray studies, performed in several model systems, have identified
      classes of genes that are sleep-state regulated. This has led to the following
      concepts: first, a function of sleep is to maintain synaptic homeostasis; second,
      sleep is a stage of macromolecule biosynthesis; third, extending wakefulness
      leads to downregulation of several important metabolic pathways; and, fourth,
      extending wakefulness leads to endoplasmic reticulum stress. In human studies,
      microarrays are being applied to the identification of biomarkers for sleepiness
      and for the common debilitating condition of obstructive sleep apnea.

PMID- 19162551
TI  - Atypical human trypanosomiasis: a neglected disease or just an unlucky accident?

PMID- 19162553
TI  - Self-care behaviour and factors associated with patient outcomes following same
      day discharge percutaneous coronary intervention.
AB  - BACKGROUND: The demand for percutaneous coronary intervention (PCI) exerts
      constant pressure on health care systems to meet the growing needs of patients.
      The practice of same-day discharge PCI has emerged as a medically safe option to
      optimize resource utilization and improve access to care. AIM: The purpose of
      this study was to describe elective same-day discharge PCI patients' self-care
      behaviour in the two to five days following their procedure, and the factors
      associated with cardiac self-efficacy (CSE) and self-care agency (SCA). METHODS:
      Using a cross-sectional correlational design, 98 consecutive patients were
      contacted by telephone, following PCI, and asked about their CSE, SCA, and
      adherence to discharge recommendations. Associations between selected variables
      were explored through multiple regression analysis. RESULTS: The findings
      revealed a high degree of adherence to discharge recommendations, although
      participants' appreciation of the long term management of their chronic disease
      was limited. Factors associated with lower levels of CSE and SCA included the
      burden of having additional chronic co-morbidities, living alone and lacking
      social support, and a positive screening for psychosocial distress. CONCLUSION:
      Same-day discharge PCI presents a sustainable option for delivery of care for
      most patients. Some clients may require additional support to manage the
      transition between acute intervention and chronic disease management.

PMID- 19162554
TI  - Regulatory T cell dysfunction in subjects with common variable immunodeficiency
      complicated by autoimmune disease.
AB  - Approximately 25% of subjects with common variable immunodeficiency (CVID)
      develop autoimmune disease. We analyzed T cell subsets, specifically regulatory T
      cells along with B cell subsets to determine whether there were changes in
      regulatory T cells which would correlate with the autoimmune disease clinical
      phenotype in CVID subjects. We hypothesized that regulatory T cell
      (CD4+CD25hiCD127lo) suppressive function would be impaired in CVID subjects with
      autoimmune disease. Using purified, sorted Treg from CVID subjects (n=14) and
      from healthy controls (HC, n=5) in standard suppression assays, we found the
      suppressive function of Treg from CVID subjects with autoimmune disease (CVID w/
      AI, n=8) to be significantly attenuated compared to CVID subjects with no
      autoimmune disease (CVID w/o AI, n=6) and to HC (n=5). A number of proteins
      associated with Treg function were decreased in expression as detected through
      immunofluorescent antibody via flow cytometry (mean fluorescence intensity (MFI)
      of FoxP3, Granzyme A, XCL1, pSTAT5, and GITR in Treg was significantly lower (by
      up to 3 fold) in CVID w/ AI compared to CVID w/o AI and HC. Furthermore, a
      statistically significant correlation was found between intracellular MFI of
      FoxP3, Granzyme A, and pSTAT5 in Treg and the degree of Treg dysfunction. These
      results suggest that attenuation of Treg function is associated with autoimmune
      disease in CVID subjects and may contribute to autoimmune pathogenesis.

PMID- 19162555
TI  - GAD and IA-2 autoantibody detection in type 1 diabetic patient saliva.
AB  - Some attempts have been made in assaying glutamic-acid decarboxylase
      autoantibodies (GADA) in type 1 diabetic patient (T1DM) saliva. However, these
      salivary assays did not show sufficient sensitivity and specificity in comparison
      to serum assays. In this study we evaluated the ability of a fluid-phase (35)S
      radioimmunoassay to detect GADA and tyrosine phosphatase 2 autoantibodies (IA-2A)
      in 70 T1DM, 24 T1DM first degree relatives (FDR) and 76 healthy subject saliva.
      Paired saliva and serum samples were collected from each subject and analyzed.
      GADA were detected in 45/70 (64.3%) sera and 43/70 (61.4%) T1DM saliva,
      respectively. IA-2A were detected in 33/70 (47.1%) sera and 30/70 (42.9%) T1DM
      saliva, respectively. All FDR serum/saliva samples were autoantibody negative. In
      conclusion, we here report that GADA and IA-2A are detectable with high
      sensitivity and specificity in human saliva, a specimen which can be easily
      collected by non-invasive procedures and may represent a reliable tool for the
      study of T1DM autoimmunity.

PMID- 19162556
TI  - Memory B-cells in healthy and antibody-deficient children.
AB  - Recently it has become clear that a reduction of IgD-CD27+ memory B-cells in
      adult CVID patients correlates with clinical aspects of the disease. However,
      little is known about B-cell dysregulation in pediatric antibody deficiency.
      Reference values are essential for the interpretation of B-cell subpopulations in
      children. We present the clinical and immunophenotypical characterization of 16
      children and adolescents with CVID and hypogammaglobulinemia. Reference values
      for IgD+CD27-, IgD+CD27+ and IgD-CD27+ B-cells in healthy children were
      established for five age groups. In healthy controls we found a continuous
      increase in IgD-CD27+ B-cell percentage with age from 1.35-5% of B-cells in the
      second year of life to 4.1-18.7% in adolescents. Interestingly, in 12/14 antibody
      deficient patients memory B-cells are significantly below the age-related 10th
      percentile. We conclude that the reduction of memory B-cells is a useful
      additional marker for the detection of children with CVID hypogammaglobulinemia
      and may contribute to the early presentation.

PMID- 19162557
TI  - Reverse swing direction regarding golf and spine.

PMID- 19162558
TI  - Dupatta type injury in the West.

PMID- 19162559
TI  - Are diabetes, hypertension, and obesity independent risk factors for endometrial
      polyps?
AB  - STUDY OBJECTIVE: To investigate whether diabetes, hypertension (HTN), and obesity
      can be considered risk factors for endometrial polyps (EPs) independently of age
      and menopausal status. DESIGN: Retrospective analysis (Canadian Task Force
      classification III). SETTING: Department of Obstetrics and Gynecology of the
      University of Foggia, Italy. PATIENTS: A total of 353 Caucasian women undergoing
      office hysteroscopy to assess abnormal uterine bleeding, infertility, cervical
      polyps, and abnormal sonographic patterns. INTERVENTIONS: Demographic
      characteristics and data on diabetes, HTN, and menopausal status were collected
      and anthropometric parameters were analyzed. Vaginoscopic hysteroscopy was
      performed with a 5-mm continuous-flow operative office hysteroscope. When
      present, EPs were treated during the same procedure by means of 5-Fr scissors or
      electrode. MEASUREMENTS AND MAIN RESULTS: In 134 (38%) of 353 cases, EPs were
      found. Univariable and multivariable analysis were performed to verify the
      presence of a statistically significant association among age, menopause, HTN,
      obesity, diabetes (independent variables), and the presence of EPs. Univariable
      logistic analysis showed a statistically significant association among age,
      menopause, HTN, obesity, and the presence of EPs. However, when multivariable
      logistic regression was performed, all the independent variables, except age,
      lost statistical significance (OR 1.05, 95% CI 1.02-1.07, p <.001). CONCLUSION:
      Although it appears that EP is a disorder of aging, the significance of diabetes,
      HTN, and obesity, as well as menopause, on the development of EPs should be
      reconsidered.

PMID- 19162560
TI  - Does well-harmonized homeostasis exist in heart rate fluctuations? Time series
      analysis and model simulations.
AB  - Analyzing heart rate variability from electrocardiographic recordings has been an
      important method for assessing cardiovascular autonomic regulation. Researchers
      have conducted extensive analyses on normal as well as pathological hearts,
      however, it is still unclear whether increasing or decreasing the complexity of
      heart rate variability is a characteristic of healthy systems. In this study, we
      find the existence of well-harmonized homeostasis in heart rate fluctuations, in
      particular, the evidence is verified among different individuals including
      healthy subjects, ICU patients, and one child with brainstem dysfunction. The
      methodology we used is composed of two parts, in which one is the consideration
      of reduction of cardiorespiratory fluctuations inherited in the original R-R
      intervals and the other is based upon the concept of nonlinear dynamics to
      construct the low-dimensional trajectory in the angle plot. The cross-correlation
      measure between the theoretical angle map and the numerically derived angle
      trajectory is used to separate recovery (0.73+/-0.13) from deterioration (0.25+/
      0.08) of ICU patients. In addition, a simple physiologic (deterministic) model of
      the interaction between the cardiovascular system and baroreceptor control of
      arterial pressure is used to explain why homeostasis can exist in heart rate
      fluctuations. Our study provides a potential link between the clinical data and
      circulatory system.

PMID- 19162561
TI  - The influence of estrogen and progesterone on parasympathetic vasodilatation in
      the rat submandibular gland.
AB  - Previous studies suggest that NO- and PGI(2)-independent pathways play a greater
      role in parasympathetic vasodilatation in the submandibular glands (SMG) of
      female than of male rats. Thus, the purpose of this study was to determine
      whether estrogen and progesterone influence the relative contributions of NO and
      PGI(2) to parasympathetic vasodilatation in the SMG. Vascular responses to chorda
      lingual nerve stimulation were examined in sham-operated (SHAM) and
      ovariectomized (OVX) female rats and in OVX rats treated with either 17beta
      estradiol alone or a combination of 17beta-estradiol and progesterone. Compared
      with SHAM animals, increases in vascular conductance in OVX rats were reduced at
      1, 2 and 5 Hz (p<0.05). Blood flow responses in OVX+17beta-estradiol and
      OVX+17beta-estradiol+progesterone rats were indistinguishable from those observed
      in SHAM animals. Indomethacin had no effect on vasodilatation in SHAM and
      OVX+17beta-estradiol rats, but increased vascular responses in OVX animals
      (p<0.02). The addition of L-NAME resulted in a significant reduction in
      vasodilatation at all frequencies. In OVX rats treated with both estrogen and
      progesterone, indomethacin caused a reduction in vasodilatation and L-NAME
      further diminished the remaining responses. Under all conditions, vasodilatation
      was due largely, if not exclusively, to direct parasympathetic rather than
      antidromic sensory nerve activation. Finally, both neuronally-derived and
      endothelium-derived NO appeared to be responsible for the NO-dependent
      vasodilatation, but endothelium-derived NO became increasingly important as the
      frequency of stimulation increased. We conclude that estrogen and progesterone
      influence parasympathetic vasodilatation through combined effects on NO-, PGI(2)-
      and non-NO/PGI(2)-mediated pathways.

PMID- 19162562
TI  - omega-Conotoxin-GVIA-sensitive calcium channels on preganglionic nerve terminals
      in mouse pelvic and celiac ganglia.
AB  - Release of acetylcholine (ACh) from preganglionic nerve terminals requires
      calcium entry through voltage-gated calcium channels. The calcium channel subtype
      required for ACh release varies depending on the particular ganglionic synapse. I
      have investigated the functional role of calcium channels in transmitter release
      from parasympathetic and sympathetic preganglionic terminals in pelvic and celiac
      ganglia of female mice. Single electrode voltage clamp was used to measure EPSC
      amplitude in the absence and presence of selective calcium channel antagonists.
      In pelvic ganglia omega- conotoxin GVIA, a selective N-type calcium channel
      antagonist, reduced the amplitude of EPSCs evoked by pelvic nerve stimulation by
      46+/-5% (n=8, P=0.015). In contrast, in the celiac ganglion, omega- conotoxin
      GVIA had no effect on the amplitude of EPSCs evoked by splanchnic nerve
      stimulation (P=0.09, n=7). EPSCs in both pelvic and celiac ganglia were resistant
      to the P-type calcium channel antagonist agatoxin (50 nM, n=5 for both ganglia)
      and the R-type calcium channel antagonist SNX482 (100 nM, n=4 for both ganglia).
      These results indicate that in female mice, release of ACh in sympathetic
      pathways to prevertebral ganglia does not require calcium entry from N-type
      calcium channels. However, release of ACh from sacral parasympathetic
      preganglionic neurons requires calcium entry from both N-type and toxin-resistant
      calcium channels.

PMID- 19162563
TI  - Steady-state bioluminescence of bacterial luciferase using electrochemical
      regeneration of flavin substrate and its application to inhibitory analysis.
AB  - The model system for the biological reaction using a bacterial luciferase (BL)
      was developed and applied to the inhibitory analysis of the hydrophobic molecules
      for enzymatic reactions. The homemade flow electrochemical luminescence cell was
      embedded in the BL reaction system to regenerate the reduced form of the flavin
      mononucleotide, which is one of the substrates of the BL luminescence reaction,
      and to measure the luminescence intensity. The constant intensity of the
      continuous BL luminescence was observed using the continuous-flow BL reaction
      system. The proposed system was successfully applied to the inhibitory reaction
      of dodecaneamide on the BL luminescence reaction.

PMID- 19162565
TI  - Insights into the cellular role of enigmatic DNA polymerase iota.
AB  - It has been a decade since the discovery of human DNA polymerase iota (poliota).
      Since that time, the enzyme has been characterized extensively at the biochemical
      level, but the cellular function of poliota remains enigmatic. Recent studies on
      poliota have, however, provided much needed insights into its biological role(s)
      and suggest that the enzyme plays important functions in protecting humans from
      the deleterious consequences of exposure to both oxidative- and ultraviolet light
      induced DNA damage.

PMID- 19162564
TI  - DNA repair modulates the vulnerability of the developing brain to alkylating
      agents.
AB  - Neurons of the developing brain are especially vulnerable to environmental agents
      that damage DNA (i.e., genotoxicants), but the mechanism is poorly understood.
      The focus of the present study is to demonstrate that DNA damage plays a key role
      in disrupting neurodevelopment. To examine this hypothesis, we compared the
      cytotoxic and DNA damaging properties of the methylating agents
      methylazoxymethanol (MAM) and dimethyl sulfate (DMS) and the mono- and
      bifunctional alkylating agents chloroethylamine (CEA) and nitrogen mustard (HN2),
      in granule cell neurons derived from the cerebellum of neonatal wild type mice
      and three transgenic DNA repair strains. Wild type cerebellar neurons were
      significantly more sensitive to the alkylating agents DMS and HN2 than neuronal
      cultures treated with MAM or the half-mustard CEA. Parallel studies with neuronal
      cultures from mice deficient in alkylguanine DNA glycosylase (Aag(-/-)) or O(6)
      methylguanine methyltransferase (Mgmt(-/-)), revealed significant differences in
      the sensitivity of neurons to all four genotoxicants. Mgmt(-/-) neurons were more
      sensitive to MAM and HN2 than the other genotoxicants and wild type neurons
      treated with either alkylating agent. In contrast, Aag(-/-) neurons were for the
      most part significantly less sensitive than wild type or Mgmt(-/-) neurons to MAM
      and HN2. Aag(-/-) neurons were also significantly less sensitive than wild type
      neurons treated with either DMS or CEA. Granule cell development and motor
      function were also more severely disturbed by MAM and HN2 in Mgmt(-/-) mice than
      in comparably treated wild type mice. In contrast, cerebellar development and
      motor function were well preserved in MAM-treated Aag(-/-) or MGMT-overexpressing
      (Mgmt(Tg+)) mice, even as compared with wild type mice suggesting that AAG
      protein increases MAM toxicity, whereas MGMT protein decreases toxicity.
      Surprisingly, neuronal development and motor function were severely disturbed in
      Mgmt(Tg+) mice treated with HN2. Collectively, these in vitro and in vivo studies
      demonstrate that the type of DNA lesion and the efficiency of DNA repair are two
      important factors that determine the vulnerability of the developing brain to
      long-term injury by a genotoxicant.

PMID- 19162566
TI  - Use of the insulin pump in treat cystic fibrosis related diabetes.
AB  - OBJECTIVES: This study was conducted to determine efficacy and tolerability of
      the continued subcutaneous insulin infusion (CSII) via an insulin pump for
      treatment of Cystic Fibrosis Related Diabetes (CFRD). We also tested the
      hypothesis that CSII would improve body weight, blood sugar control, lean body
      mass, whole body protein turnover, hepatic glucose production (HGP). METHODS: We
      recruited 9 CF patients with established diabetes and placed them on insulin pump
      therapy for six months. Each subject kept daily blood sugar records before and
      during pump use. Prior to the pump placement and at the end of six months, each
      patient underwent the following measurements: 1) whole body protein turnover
      using the stable isotope [1-(13)C] leucine; 2) DEXA scan for measurement of lean
      body mass; 3) anthropometric measurements; 4) Hemoglobin A1c. Patient data was
      compared to baseline data and the mean change from baseline was analyzed.
      RESULTS: There was significant improvement in both fasting and post-prandial
      blood glucose levels, body weight, HbA1C, and lean mass. Protein catabolism as
      measured by leucine rate of appearance was significantly lower, as was hepatic
      glucose production. No patient developed hypoglycemia during the study.
      CONCLUSIONS: This study demonstrates that CSII is safe and effective for
      treatment of CFRD and that metabolic benefits are also present.

PMID- 19162567
TI  - Remediation of undesirable secondary interactions encountered in hydrophilic
      interaction chromatography during development of a quantitative LC-MS/MS assay
      for a dipeptidyl peptidase IV (DPP-IV) inhibitor in monkey serum.
AB  - PF-00734200 (3,3-Difluoropyrrolidin-1-yl)-((2S,4S)-4-(4-(pyrimidin-2-yl)
      piperazin-1-yl)pyrrolidin-2-yl)methanone) is an inhibitor of dipeptidyl peptidase
      IV (DPP-IV) for the treatment of diabetic complications and other disorders. A
      sensitive and selective LC-MS/MS assay capable of quantifying PF-00734200 in
      monkey serum was required to support regulated safety studies. Due to the polar
      nature of this compound and for ease of sample processing, hydrophilic
      interaction chromatography (HILIC) was identified as an ideal assay technique.
      During the initial phase of method development significant peak tailing was
      observed. The effects of polar organic modifier percentage, buffer concentration,
      column particle size, and flow rate were assessed to determine the final optimal
      conditions. PF-00734200 demonstrated a strong dependence on buffer concentration
      with respect to height equivalent to a theoretical plate (HETP), capacity factor
      (k'), and tailing factor (T). Improvements in chromatography were observed with
      increasing buffer concentration due to reduction of electrostatic secondary
      interactions with ionized silanols. A plot of logk' versus percentage organic
      modifier at an elevated buffer concentration, produced a linear fit with a
      correlation coefficient of 0.996, indicating that the primary chromatographic
      retention mechanism was partitioning. A LC-MS/MS assay was successfully developed
      and validated for GLP bioanalysis of PF-00734200 in monkey serum utilizing the
      optimized HILIC conditions. Additionally, carryover was effectively minimized
      through fortification of ethylene glycol to the sample extract.

PMID- 19162568
TI  - Application of a liquid chromatography/tandem mass spectrometry method for the
      pharmacokinetic study of dihydroartemisinin injectable powder in healthy Chinese
      subjects.
AB  - A simple, rapid and accurate liquid chromatography-electrospray ionization-tandem
      mass spectrometry method was developed and validated for quantification of
      dihydroartemisinin (DHA) in human plasma. Following a simple single-step liquid
      liquid extraction with ethyl acetate, the analyte was separated on a C(18) column
      by isocratic elution with methanol-water-10mM ammonium acetate (80:10:10, v/v/v),
      and analyzed by mass spectrometry in the positive ion MRM mode. Good linearity
      was achieved over a wide range of 1.01-2020ng/mL. Intra- and inter-day precisions
      were less than 9.0%, and accuracy ranged from 93.0 to 98.2%. The pharmacokinetics
      of DHA injectable powder was studied for the first time in healthy subjects by
      this method. After single intravenous infusion of DHA injectable powder 40, 80
      and 160mg, the elimination half-life (t(1/2lambdaZ)) was 1.69, 1.88 and 1.92h,
      respectively; mean C(max) and AUC increased in proportion to the doses. The
      pharmacokinetics of DHA fit the linear dynamic feature over the DHA dose range
      studied.

PMID- 19162569
TI  - Specific GC-MS/MS stable-isotope dilution methodology for free 9- and 10-nitro
      oleic acid in human plasma challenges previous LC-MS/MS reports.
AB  - Nitrated unsaturated fatty acids including nitro-oleic acid (NO(2)-OA) have been
      measured in human blood samples in their free and esterified forms. Plasma
      concentrations in healthy subjects have been reported to be of the order of 600
      nM for free NO(2)-OA and 300 nM for esterified NO(2)-OA, as measured by LC-MS/MS.
      In the present article we report a GC-MS/MS method for the specific and accurate
      quantification of two NO(2)-OA isomers, i.e., 9-NO(2)-OA and 10-NO(2)-OA, in
      human plasma using newly prepared, isolated, characterized and standardized (15)N
      labeled analogs. This method involves SPE extraction of fatty acids from slightly
      acidified plasma samples (pH 5), conversion to their pentafluorobenzyl (PFB)
      esters, isolation by HPLC, solvent extraction from a single HPLC fraction and GC
      MS/MS analysis in the electron capture negative-ion chemical ionization (ECNICI)
      mode. Quantification was performed by selected-reaction monitoring (SRM) of m/z
      46 ([NO(2)](-)) and m/z 47 ([(15)NO(2)](-)) produced by collision-induced
      dissociation (CID) from the parent ions [M-PFB](-) at m/z 326 for endogenous 9
      NO(2)-OA and 10-NO(2)-OA and m/z 327 for the internal standards 9-(15)NO(2)-OA
      and 10-(15)NO(2)-OA. We partially validated the GC-MS/MS method for 9-NO(2)-OA
      and 10-NO(2)-OA in human plasma and quantified these nitro-oleic species in
      plasma of 15 healthy volunteers. We identified two isomers, i.e., 9-NO(2)-OA and
      10-NO(2)-OA, in human plasma under physiological conditions and found these
      nitrated fatty acids at a mean concentration of 1 nM each. This concentration is
      about 600 times lower than that reported by others using LC-MS/MS. Our GC-MS/MS
      studies on nitro-oleic acid and 3-nitrotyrosine suggest that the extent of
      nitration of biomolecules such as unsaturated fatty acids and tyrosine is very
      low in health. In this article we discuss analytical and biological ramifications
      potentially associated with measurement of nitrated biomolecules in biological
      systems.

PMID- 19162570
TI  - Determination of biogenic amines in beer with pre-column derivatization by high
      performance liquid chromatography.
AB  - Eighteen samples of commercially available Chinese beer were analyzed in order to
      determine the content of biogenic amines. The method involves pre-column
      derivatization of the amines with 4-chloro-3,5-dinitrobenzotrifluoride (CNBF) and
      subsequent analysis by RP-HPLC (reversed phase-high performance liquid
      chromatography) with diode array detection. The labeled biogenic amines were
      separated on a Kromasil C18 column (250mmx4.6mm, 5microm) at room temperature and
      UV detection was applied at 254nm. The separation of seven labeled biogenic
      amines was achieved within 22min by elution acetonitrile and HAc-NaAc buffers.
      The method linearity, calculated for each biogenic amine, has a correlation
      coefficient higher than 0.9925, in concentrations ranging from 2.9micromolL(-1)
      to 565micromolL(-1). Detection limits of biogenic amines were 0.056
      0.87micromolL(-1), at a signal-to-noise ratio of 3. The proposed method has been
      applied to the quantitative determination of spermine, phenethylamine,
      spermidine, histamine, tyramine, tryptamine and putrescine in beer with
      recoveries of 91.9-103.1% and R.S.D. of 2.86-5.63%. Quantitation is relative to
      external standards. The results showed that each kind of beer examined contained
      at least three biogenic amines. Putrescine, histamine and tyramine were detected
      in all samples. Spermidine was detected in 89% of the beers. Spermine, tryptamine
      and phenylethylamine occurred in 78%, 61% and 44% of the beers examined,
      respectively. These levels were below the level that may elicit direct adverse
      reactions for most consumers.

PMID- 19162571
TI  - Determination of eptifibatide concentration in human plasma utilizing the liquid
      chromatography-tandem mass spectrometry method.
AB  - A sensitive and selective liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method was developed to determine the concentration of eptifibatide in
      human plasma. Following protein precipitation, the analyte was separated on a
      reversed-phase C(18) column. Acetonitrile:5mM ammonium acetate:acetic acid
      (30:70:0.1, v/v/v) was used at a flow-rate of 0.5mL/min with the isocratic mobile
      phase. An API 4000 tandem mass spectrometer equipped with a Turbo IonSpray
      ionization source was used as the detector and was operated in the positive ion
      mode. "Truncated" multiple reaction monitoring using the transition of m/z 832.6-
      >m/z 832.6 and m/z 931.3-->m/z 931.3 was performed to quantify eptifibatide and
      the internal standard (EPM-05), respectively. The method had a lower limit of
      quantification of 4.61ng/mL for eptifibatide. The calibration curve was
      demonstrated to be linear over the concentration range of 4.61-2770ng/mL. The
      intra- and inter-day precisions were less than 10.5% for each QC level, and the
      inter-day relative errors were 2.0%, 5.6%, and 2.8% for 9.22, 184, and 2490ng/mL,
      respectively. The validated method was successfully applied to the quantification
      of eptifibatide concentration in human plasma after intravenous (i.v.)
      administration of a 270-microg/kg bolus of eptifibatide and i.v. administration
      of eptifibatide at a constant rate of infusion of 2microg/(kgmin) for 18h in
      order to evaluate the pharmacokinetics.

PMID- 19162572
TI  - Expanded bed adsorption of an alkaline lipase from Pseudomona cepacia.
AB  - An extracellular lipase was isolated from Pseudomona cepacia by expanded bed
      adsorption on an Amberlite 410 ion-exchange resin. Enzyme characterization and
      hydrodynamic study of a chromatography column were done. Enzyme purification was
      done at three condition of expanded bed height (H): at one and half (6cm), at two
      (8cm) and at three (12cm) times the fixed bed height (H(0)=4cm). The results
      showed that the experimental data was fitted to the Richardson and Zaki equation,
      and the comparison between the experimental and calculated terminal velocities
      showed low relative error. In enzyme purification for better condition, a
      purification factor of about 80 times was found at 6cm of expanded bed height, or
      1.5 times of expansion degree. Purified lipase had an optimal pH and a
      temperature of 8 and 37 degrees C, respectively.

PMID- 19162573
TI  - How do we interpret an elevated carbohydrate antigen 19-9 level in asymptomatic
      subjects?
AB  - AIM: This prospective cohort study aimed to evaluate the etiology of elevated CA
      19-9 levels and to present appropriate guidelines for the asymptomatic patients.
      METHODS: Between January 2004 and March 2007, we enrolled consecutive
      asymptomatic patients who had elevated CA 19-9 levels >37 U/mL. To evaluate the
      etiology, the CA 19-9 level was rechecked and further studies were carried out.
      If the CA 19-9 level decreased to the normal range, or if it showed a decreasing
      trend, then it was monitored annually. Yet, if the CA 19-9 level showed an
      increasing trend, then the level was monitored at intervals of 1, 3, and 6 months
      until no evidence of malignancy was proven. RESULTS: Of the 62,976 patients, 501
      (0.8%) subjects showed an elevated CA 19-9 level. This prospective analysis was
      conducted on 353 subjects (70.5%) who were followed up for at least 6 months. Ten
      patients (2.8%) were diagnosed with malignancies. There were 97 patients (27.5%)
      with benign diseases and 246 patients (69.7%) were deemed non-specific.
      CONCLUSIONS: CA 19-9 should not be used as a screening tool. In the case of a
      persistently elevated CA 19-9 level, further work-up for determining the etiology
      should be done.

PMID- 19162574
TI  - Immune-mediated liver dysfunction after antiviral treatment in liver transplanted
      patients with hepatitis C: allo or autoimmune de novo hepatitis?
AB  - BACKGROUND: The recurrence of hepatitis C after liver transplantation is
      extremely frequent. Antiviral therapy combining pegylated-interferon with
      ribavirin is therefore increasingly used in these patients. It has been recently
      reported, however, that during antiviral treatment a hepatic immune-mediated
      liver dysfunction, similar to "de novo" autoimmune hepatitis, may develop in a
      few transplanted patients. PATIENTS AND METHODS: Three patients, treated with
      pegylated-interferon alpha-2a and ribavirin for recurrent hepatitis C after liver
      transplantation, developed an aggressive hepatitis with clinical, biochemical,
      and histological features similar to those of autoimmune hepatitis. RESULTS: In
      all three patients, a liver enzymes increase was evident after hepatitis C virus
      RNA had become undetectable. Diagnosis of "de novo" autoimmune hepatitis was
      proposed, based on the presence of high-titre circulating autoantibodies and
      liver histology features. Following the introduction of a steroid therapy,
      clinical and biochemical parameters progressively improved. Hepatitis C virus
      infection, however, relapsed after a few months in all the patients. CONCLUSIONS:
      Following liver transplantation, antiviral therapy with pegylated-interferon
      alpha-2a and ribavirin for recurrent hepatitis C may be associated, in a few
      patients, with severe immune-mediated graft dysfunction similar to autoimmune
      hepatitis.

PMID- 19162576
TI  - Cosmetic treatments: an emerging field of interest for interventional
      radiologists.
AB  - The current trend in medical care in the 21st century is evolving into a
      minimally invasive specialty. The interest of Interventional Radiology (IR) in
      cosmetic is increasing particularly for outsetting patients, in the treatment of
      soft tissue vascular malformations, us-guided injections of Botox and varicous
      veins management. Advantages of cosmetic IR treatments are many: treatments takes
      less than an hour and provides immediate relief of symptoms; no scaring, because
      the procedure does not require a surgical incision; an immediate return to normal
      activity with little or no pain; and high success rate and low recurrence rate
      compared to surgery.

PMID- 19162577
TI  - Breast cancer imaging and stroke monitoring with diffuse optics.

PMID- 19162575
TI  - Biofunctionalized electrospun silk mats as a topical bioactive dressing for
      accelerated wound healing.
AB  - Materials able to deliver topically bioactive molecules represent a new
      generation of biomaterials. In this article, we describe the use of silk mats,
      made of electrospun nanoscale silk fibers containing epidermal growth factor
      (EGF), for the promotion of wound healing processes. In our experiments, we
      demonstrated that EGF is incorporated into the silk mats and slowly released in a
      time-dependent manner (25% EGF release in 170h). We tested these materials using
      a new model of wounded human skin-equivalents displaying the same structure as
      human skin and able to heal using the same molecular and cellular mechanisms
      found in vivo. This human three-dimensional model allows us to demonstrate that
      the biofunctionalized silk mats, when placed on the wounds as a dressing, aid the
      healing by increasing the time of wound closure by the epidermal tongue by 90%.
      The preservation of the structure of the mats during the healing period as
      demonstrated by electronic microscopy, the biological action of the dressing, as
      well as the biocompatibility of the silk demonstrate that this biomaterial is a
      new and very promising material for medical applications, especially for patients
      suffering from chronic wounds.

PMID- 19162578
TI  - Intravascular ultrasound and photoacoustic imaging.
AB  - There is a need for an imaging technique that can reliably identify and
      characterize the vulnerability of atherosclerotic plaques. Catheter-based
      intravascular ultrasound (IVUS) is one of the imaging tools of the clinical
      evaluation of atherosclerosis. However, histopathological information obtained
      with IVUS imaging is limited. We present and discuss the applicability of a
      combined intravascular photoacoustic (IVPA) and intravascular ultrasound (IVUS)
      imaging approach to assess both vessel structure and tissue composition thus
      identifying rupture-prone atherosclerotic plaques. Photoacoustic (or optoacoustic
      and, generally, thermoacoustic) imaging relies on the absorption of
      electromagnetic energy, such as light, and the subsequent emission of an acoustic
      wave. Therefore, the amplitude and temporal characteristics of the photoacoustic
      signal is primarily determined by optical absorption properties of different
      types of tissues and can be used to differentiate the lipid, fibrous and fibro
      cellular components of an inflammatory lesion. Simultaneous IVUS and IVPA imaging
      studies were conducted using 40 MHz clinical IVUS imaging catheter interfaced
      with a pulsed laser system. The performance of the IVPA/IVUS imaging was assessed
      using phantoms with point targets and vessel-mimicking phantoms. To detect the
      lipids in the plaque, ex-vivo IVPA imaging studies of a normal and an
      atherosclerotic rabbit aorta were performed at a 532 nm wavelength. To assess
      plaque composition, multi-wavelength (680-950 nm) spectroscopic IVPA imaging
      studies were carried out. Finally, molecular and cellular IVPA imaging was
      demonstrated using plasmonic nanoparticles. Overall, our studies suggest that
      plaque detection and characterization can be improved using the combined
      IVPA/IVUS imaging.

PMID- 19162579
TI  - Converging micro-nano-bio technologies towards integrated biomedical systems:
      state of the art and future perspectives under the EU-information & communication
      technologies program.
AB  - Research and development at the convergence of microelectronics, nano-materials,
      biochemistry, measurement technology and information technology is leading to a
      new class of biomedical systems and applications e.g. molecular imaging, point of
      care testing, gene therapy and bionics (including on and inside the body sensors
      and other miniaturised smart systems) which are expected to revolutionise the
      healthcare provision and quality of life. In particular they are expected to
      identify diseases at the earliest possible stage, intervene before symptomatic
      disease becomes apparent and monitor both the progress of the diseases and the
      effect of intervention and therapeutic procedures. The group of EC-funded
      projects on Micro-Nano-Bio Convergence Systems, "so-called" MNBS, is made by
      projects developing systems that use a vast array of technologies to integrate
      across traditional boundaries between the micro-nano-bio, and info worlds,
      enabling a wide range of applications from health care to food quality
      monitoring. It includes mainly two sub-groups, one dealing with systems for in
      vitro molecular diagnosis and biological/biochemical analysis and the other is
      dealing with systems for in vivo interaction with the human body. Current status
      of development and future challenges, technological and socioeconomic, are
      briefly presented in this paper as background introductory information to the
      mini-symposium on MNBS. Relevant examples of R&D within the group will be
      presented in the mini-symposium.

PMID- 19162580
TI  - Major developments on smart implants and diagnostic equipment.

PMID- 19162581
TI  - SmartHEALTH: a multisensor platform for POC cancer diagnostics.

PMID- 19162582
TI  - Application of filtering methods for removal of resuscitation artifacts from
      human ECG signals.
AB  - Band-pass, Kalman, and adaptive filters are used for removal of resuscitation
      artifacts from human ECG signals. A database of separately recorded human ECG and
      animal resuscitation artifact signals is used for evaluation of the methods. The
      considered performance criterion is the signal-to-noise ratio (SNR) improvement,
      defined as the ratio of the SNRs of the filtered signal and the given ECG signal.
      The empirical results show that for low SNR of the given signal, a band-pass
      filter yields the best performance, while for high SNR, an adaptive filter yields
      the best performance.

PMID- 19162583
TI  - Low complexity tracking for long term monitoring of heart sounds.
AB  - This paper describes a novel framework for tracking heart sounds. For a given
      heart sound component (e.g. S1) candidate features (e.g. peaks) are mapped to
      states and assigned appropriate local scores. A low complexity dynamic
      programming based algorithm is developed to select the largest most consistent
      feature from the candidate features. This algorithm is also capable of detecting
      multiple simultaneous features for improved noise immunity. The proposed
      algorithm has linear complexity with time and cubic complexity with the number of
      features to be tracked. Data from six swine balloon-occlusion studies are used
      for preliminary testing of the algorithm. The S1 amplitude and heart sound
      ejection time (HSET) are found to be statistically significantly correlated with
      changes in systolic performance due to ischemia induction.

PMID- 19162584
TI  - Reduction of skin reflections in radar-based microwave breast imaging.
AB  - Radar-based microwave breast imaging is a prospective complementary imaging
      method that relies on dielectric property differences. One of the main challenges
      is removing the overwhelming reflection associated with the skin. In this paper,
      a skin subtraction method that can be applied to data generated with a realistic
      three dimensional breast model is presented. The method estimates the skin
      response of the target antenna as a filtered combination of its neighbors with
      the use of a modified recursive least squares algorithm and a generalized cross
      validation technique. The neighbors are selected based on their proximity and
      their spatial correlation to the target antenna. The method's ability to subtract
      the skin response and preserve the tumor response is demonstrated.

PMID- 19162585
TI  - Equalizing secondary path effects using the periodicity of fMRI acoustic noise.
AB  - Non-minimum phase secondary path has a direct effect on achieving a desired noise
      attenuation level in active noise control (ANC) systems. The adaptive noise
      canceling filter is often a causal FIR filter which may not be able to
      sufficiently equalize the effect of a non-minimum phase secondary path, since in
      theory only a non-causal filter can equalize it. However a non-causal stable
      filter can be found to equalize the non-minimum phase effect of secondary path.
      Realization of non-causal stable filters requires knowledge of future values of
      input signal. In this paper we develop methods for equalizing the non-minimum
      phase property of the secondary path and improving the performance of an ANC
      system by exploiting the periodicity of fMRI acoustic noise. It has been shown
      that the scanner noise component is highly periodic and hence predictable which
      enables easy realization of non-causal filtering. Improvement in performance due
      to the proposed methods (with and without the equalizer) is shown for periodic
      fMRI acoustic noise.

PMID- 19162586
TI  - Multiharmonic tracking using marginalized particle filters.
AB  - Man-made and natural systems often generate signals with multi-harmonic
      components, and the accurate estimation of the harmonically related components of
      these signals is critical for various applications. The posterior distribution of
      frequency estimates for this class of signal is multi-model--posing a challenge
      for frequency tracking algorithms which may lock onto a super or sub harmonic of
      the fundamental frequency. We propose a multi-harmonic tracker based on a
      sequential Monte Carlo method (SMCM) which can account for the multi-modality of
      the posterior distribution to track the harmonically related components of a
      signal more accurately than a tracker based on local linearization. We compare
      the SMCM multi-harmonic tracker with the extended Kalman filter (EKF) multi
      harmonic tracker by applying them to real biomedical signals including
      electrocardiograms (ECG) and arterial blood pressure (ABP) signals. The results
      clearly show the superior performance of the proposed multi-harmonic tracker over
      the EKF tracker.

PMID- 19162587
TI  - Recording with microchannel electrodes in a noisy environment.
AB  - Microchannels containing electrodes have a number of favourable properties that
      make them potentially suitable as the basis of a peripheral nerve interface
      design. In this study we have evaluated microchannel recording in vitro in the
      presence of a realistic simulation of electrical interference from musculature
      adjacent to an implanted interface. Tripolar recording and high-pass filtration
      both help improve signal discrimination. At high noise levels designed to
      replicate the effects of intense muscular activity, a combination of both these
      techniques is required, and only signals in larger axons can be recovered.

PMID- 19162588
TI  - Wavelet-based neural pattern analyzer for behaviorally significant burst pattern
      recognition.
AB  - Closed-loop neural prosthesis systems rely on accurately recording neural data
      from multiple neurons and detecting behaviorally meaningful patterns before
      representing them in a highly compressed form for wireless transmission over a
      limited-bandwidth link. We present a novel wavelet-based approach for detecting
      spikes, grouping them as bursts and building a dynamic vocabulary of meaningful
      burst patterns. Simulation results on pre-recorded in vivo multi-channel
      extracellular neural data from the buccal ganglion of Aplysia demonstrate the
      feasibility of behavior recognition as well as data compression (>500X) by the
      proposed approach.

PMID- 19162589
TI  - Modeling spiking activity of in vitro neuronal networks through non linear
      methods.
AB  - Neuroscience research is even more exploiting technologies developed for
      electronic engineering use: this is the case of Micro-Electrode Array (MEA)
      technology, an instrumentation which is able to acquire in vitro neuron spiking
      activity from a finite number of channels. In this work we present three models
      of synaptic neuronal network connections, called 'Full-Connected', 'Hierarchical'
      and 'Closed-Path'. Related to each one we implemented an index giving
      quantitative measures of similarity and of statistical dependence among neuron
      activities recorded in different MEA channels. They are based on Information
      Theory techniques as Mutual and Multi Information: the last one extending the
      pair-wise information to higher-order connections on the entire MEA neuronal
      network. We calculated indexes for each model in order to test the presence of
      self-synchronization among neurons evolving in time, in response to external
      stimuli such as the application of chemical neuron-inhibitors. The availability
      of such different models helps us to investigate also how much the synaptic
      connections are spatially sparse or hierarchically structured and finally how
      much of the information exchanged on the neuronal network is regulated by higher
      order correlations.

PMID- 19162590
TI  - Automated reduction of non-neuronal signals from intra-cortical microwire array
      recordings by use of correlation technique.
AB  - Implanted intra-cortical micro-electrode arrays record multi-unit extracellular
      spike activity that is used in deciphering the neural basis for adaptation,
      learning, plasticity and as command signal for brain-machine interfaces (BMI).
      Detection of spike activity is the first step in successful implementation of all
      the aforementioned applications. However, with awake and behaving animals, micro
      electrode arrays typically also record non-neuronal signals induced by the
      animal's movement, feeding and grooming actions. The spectral and temporal nature
      of these artifacts is similar to neural spikes, which complicates accurate
      detection. The distal source and higher strength of non-neuronal signals result
      in their near simultaneous registration on most electrodes, while neural spiking
      event is rarely recorded on more than one electrode of an array. This difference
      is utilized in identifying non-neuronal content from acquired data by performing
      a correlation analysis. The efficacy of the method is evaluated by comparing
      outcomes from algorithms that use absolute threshold and Principal Component
      Analysis (PCA) as a means of identifying neural spikes with the same methods
      incorporating correlation analysis.

PMID- 19162591
TI  - A hybrid algorithm for artifact rejection in EEG recordings based on iterative
      ICA and fuzzy clustering.
AB  - Brain responses to repeated sensory stimuli are typically contaminated by
      extraneous activity, including background rhythms, artifacts, and interference
      signals. To address this issue, we have recently proposed a new iterative
      independent component analysis (iICA) approach that can provide reliable evoked
      response (ER) estimates on a single trial basis. In this paper, we present a new
      two-step approach that focuses on removing well-defined artifacts, such as eye
      movements and muscle activity, before iICA processing. Extended analyses with
      both simulated data and actual recordings from normal subjects demonstrate that
      this procedure gives better results than iICA alone. Additionally, this
      methodology is suitable for fast analysis of multi-electrode recordings in
      parallel architectures, as individual channels can be processed simultaneously on
      different processors, and thus, it may have a significant impact on the analysis
      efficiency of large datasets of single-trial ERs.

PMID- 19162592
TI  - Dynamic clustering for vigilance analysis based on EEG.
AB  - Electroencephalogram (EEG) is the most commonly studied signal for vigilance
      estimation. Up to now, many researches mainly focus on using supervised learning
      methods for analyzing EEG data. However, it is hard to obtain enough labeled EEG
      data to cover the whole vigilance states, and sometimes the labeled EEG data may
      be not reliable in practice. In this paper, we propose a dynamic clustering
      method based on EEG to estimate vigilance states. This method uses temporal
      series information to supervise EEG data clustering. Experimental results show
      that our method can correctly discriminate between the wakefulness and the
      sleepiness for every 2 seconds through EEG, and can also distinguish two other
      middle states between wakefulness and sleepiness.

PMID- 19162593
TI  - The implementation of an integrated computer-aided system for dental
      implantology.
AB  - This paper presents an implementation of different functionalities on a computer
      aided system for dental implantology. The integrated system consists of two
      subsystems corresponding to two main stages of dental implantology respectively.
      In the preoperative planning subsystem, we provide different kinds of views based
      on CT data scanned from a specific patient for the dentist. And the dentist can
      plan implant path according to these views. The intra-operative navigational
      subsystem uses an infra-red light based navigation camera to locate the precise
      position of the surgical instrument. At last, an improved experiment on a phantom
      model studied the error and accuracy, to demonstrate its feasibility on further
      clinical trial.

PMID- 19162594
TI  - Surgical accuracy under virtual reality-enhanced ultrasound guidance: an in vitro
      epicardial dynamic study.
AB  - In the context of our ongoing objective to reduce morbidity associated with
      cardiac interventions, minimizing invasiveness has inevitably led to more limited
      visual access to the target tissues. To ameliorate these challenges, we provide
      the surgeons with a complex visualization environment that integrates
      interventional ultrasound imaging augmented with pre-operative anatomical models
      and virtual surgical instruments within a virtual reality environment. In this
      paper we present an in vitro study on a cardiac phantom aimed at assessing the
      feasibility and targeting accuracy of our surgical system in comparison to
      traditional ultrasound imaging for intra-operative surgical guidance. The
      'therapy delivery' was modeled in the context of a blinded procedure, mimicking a
      closed-chest intervention. Four users navigated a tracked pointer to a target,
      under guidance provide by either US imaging or virtual reality-enhanced
      ultrasound. A 2.8 mm RMS targeting error was achieved using our novel surgical
      system, which is adequate from both a clinical and engineering perspective, under
      the inherent procedure requirements and limitations of the system.

PMID- 19162595
TI  - 3-D reconstruction of a surface model of the proximal femur from digital biplanar
      radiographs.
AB  - Twenty-two femurs (one plastic bone and twenty-one cadaveric bones) with both
      nonpathologic and pathologic cases were considered to validate a point
      distribution model based three-dimensional (3-D) reconstruction technique using
      digital biplanar radiographs. The 3-D reconstruction technique is based on an
      iterative non-rigid registration of the features extracted from a statistically
      instantiated 3-D surface model to those identified from the radiographs. The
      surface models reconstructed from the radiographs were compared to the associated
      ground truths derived either from a 3-D CT-scan reconstruction method or from a 3
      D laser-scan reconstruction method. Our experimental results demonstrated that
      our biplanar reconstruction technique could accurately reconstruct the surface
      models of both nonpathologic and pathologic femurs (average error distance=0.9
      mm), even when the point distribution model that we used were constructed from
      surface models of nonpathologic femurs.

PMID- 19162596
TI  - Instrumentation of a clinical colonoscope for surgical simulation.
AB  - This paper describes the instrumentation of a clinical colonoscope needed for a
      novel colonoscopy simulation framework. The simulator consists of a compact and
      portable haptic interface and a virtual reality environment to provide real-time
      visualization. The proposed instrumentation enables tracking different functions
      of the colonoscope while keeping the ergonomics unchanged.

PMID- 19162597
TI  - Landmark based augmented reality endoscope system for sinus and skull-base
      surgeries.
AB  - Endoscopic video stream during sinus and skull base surgeries can be augmented
      with the preoperatively chosen landmark to provide effective navigation for the
      operating surgeon. Currently available systems try to augment with CT or MR image
      slices. This will be of not much help since there is too much information
      overlaid. We have developed a simplified landmark based Augmented Reality (AR)
      system for endoscopic sinus/skull-base surgeries. Results are presented from the
      experiments with plastic skull and cadaver specimen. Subjective evaluation from a
      experienced surgeon confirms the effectiveness of the system.

PMID- 19162598
TI  - Robust automatic detection and removal of fiducial projections in fluoroscopy
      images: an integrated solution.
AB  - Automatic detection and removal of fiducial projections in fluoroscopy images is
      an essential prerequisite for fluoroscopy-based navigation and image-based 3D-2D
      registration. This paper presents an integrated solution to fulfill this task. A
      custom-designed calibration cage with a two-plane pattern of fiducials is
      utilized in our solution. The cage is attached to the C-arm image intensifier and
      the projections of the fiducials are automatically detected and removed by an on
      line algorithm consisting of following 6 steps: image binarization, connected
      component labeling, region classification, adaptive template matching, shape
      analysis, and fiducial projection removal. A similarity measure which is proposed
      previously for image-based 3D-2D registration is employed in the adaptive
      template matching to improve the accuracy of the detection. Shape analysis based
      on the geometrical constraints satisfied by those fiducials in the calibration
      cage is used to further improve the robustness of the detection. An image
      inpainting technique based on the fast marching method for level set applications
      is used to remove the detected fiducial projections. Our in vitro experiments
      show on average 4 seconds execution time on a Pentium IV machine, a zero false
      detection rate, a miss-detection rate of 1.6+/-2.3%, and a sub-pixel localization
      error.

PMID- 19162599
TI  - A network flow method for improved MR field map estimation in the presence of
      water and fat.
AB  - Field map estimation is an important problem in MRI, with applications such as
      water/fat separation and correction of fast acquisitions. However, it constitutes
      a nonlinear and severely ill-posed problem requiring regularization. In this
      paper, we introduce an improved method for regularized field map estimation,
      based on a statistically motivated formulation, as well as a novel algorithm for
      the solution of the corresponding optimization problem using a network flow
      approach. The proposed method provides theoretical guarantees (local optimality
      with respect to a large move), as well as an efficient implementation. It has
      been applied to the water/fat separation problem and tested on a number of
      challenging datasets, showing high-quality results.

PMID- 19162600
TI  - An efficient temperature estimation using optical-flow in ultrasound B-mode
      digital images.
AB  - A two-dimensional temperature estimation method has been proposed based on the
      detection of shifts in speckle pattern location of ultrasound B-Mode digital
      images from a region of tissue undergoing thermal therapy. The speckle pattern
      shifts were due to the local temperature dependence of sound speed and thermal
      expansion in the heated region. Here in this paper we made use of optical-flow in
      order to achieve a better accuracy and lower computational burden. The accuracy
      of measurement of the temperature has been tested on simulated images and it is
      experimentally validated using tissue mimicking phantom. Good agreement was
      obtained from the simulated sequences (mean difference=0.1 and pick error was
      0.6). The proposed method was found computationally faster compared to our
      previous work which was based on the cross correlation algorithm.

PMID- 19162601
TI  - Voxelwise regularisation of high angular resolution diffusion imaging data.
AB  - The problem of noise suppression in high angular resolution diffusion MRI data is
      approached through direct regularisation of the apparent diffusion coefficient
      profiles. The proposed algorithm is derived in a Bayesian framework in the style
      of the traditional techniques for image restoration using Markov random field
      models. In a novel departure from the classical approach, a Markov random field
      model is applied within each voxel across gradient directions, thus smoothing the
      image data without inducing additional spatial dependencies that would render
      region-of-interest statistical testing of diffusion characteristics invalid. The
      anisotropic smoothing algorithm exploits the heterogeneous distribution of
      gradient directions and their antipodal pairs on the sphere and, in application
      to both simulated and experimental high angular resolution imaging datasets, is
      demonstrated to be superior to the isotropic Markov random field variant and the
      maximum likelihood estimator.

PMID- 19162602
TI  - Average field map image template for Echo-Planar image analysis.
AB  - Magnetic resonance field map images are normally used in characterizing the
      magnetic field inhomogeneity for distortion correction in Echo-Planar Imaging
      (EPI) and accurate localization in functional MRI (fMRI). In this paper, the
      computation and applications of an average field map image template is
      investigated based on real field maps. The introduced methodology and the
      obtained field map image templates may be used in EPI and fMRI image analysis,
      distortion correction, registration, and functional localization when high
      resolution field map images are not available for individual datasets. The
      introduced methodology involves three stages of pre-processing, registration, and
      spatial normalization. The analysis and results presented in this paper show the
      impact and usefulness of the investigated methodology in several applications.

PMID- 19162603
TI  - Parametric data mining and diagnostic rules for digital thermographs in breast
      cancer.
AB  - In this study, a novel data mining algorithm and parametric analysis protocol
      were utilized for generating knowledge-based diagnostic rules for infrared
      thermographs. First, Beier-Neely field morphing and linear affine transformation
      algorithms were used in geometric standardization for the whole body and partial
      region respectively. Gray levels of thermal images at same anatomical coordinates
      in the abnormal regions were then analyzed to determine upper and lower limits
      for diagnosis. Twenty-five parameters were extracted from each abnormal region
      for parametric analysis, and decision trees were used to generate the knowledge
      based diagnostic rules. A total of 71 and 131 female patients with and without
      breast cancer respectively were both analyzed in this study. Experimental results
      indicated that a total of 1750 abnormal regions (703 positive and 1047 negative)
      were detected. Sixty one positive abnormal regions (61/703=8.6%) from 44 cancer
      patients (42/71=59.2%) can be found in the abovementioned 14 branches.

PMID- 19162604
TI  - Periorbital thermal signal extraction and applications.
AB  - We propose a novel method that localizes the thermal footprint of the facial and
      ophthalmic arterial-venous complexes in the periorbital area. This footprint is
      used to extract the mean thermal signal over time (periorbital signal), which is
      a correlate of the blood supply to the ocular muscle. Previous work demonstrated
      that the periorbital signal is associated to autonomic responses and it changes
      significantly upon the onset of instantaneous stress. The present method enables
      accurate and consistent extraction of this signal. It aims to replace the
      heuristic segmentation approach that has been used in stress quantification thus
      far. Applications in computational psychology and particularly in deception
      detection are the first to benefit from this new technology. We tested the method
      on thermal videos of 39 subjects who faced stressful interrogation for a mock
      crime. The results show that the proposed approach has improved the deception
      classification success rate to 82%, which is 20% higher compared to the previous
      approach.

PMID- 19162605
TI  - Active sensing for viscoelastic tissue with coupling effect.
AB  - This paper discusses active sensing for detecting viscoelastic parameters of
      living tissues with the coupling effect among neighbors. Supposing that both
      applied force and surface deformation of tissue are known with respect to time,
      we obtain viscoelastic parameters of living tissue by utilizing a single layered
      model with horizontal and vertical units where each unit is composed of both
      stiffness and damping elements. We show that the model with only appropriate
      number of units can nicely express the dynamic characteristic of human skin.

PMID- 19162606
TI  - Measuring muscle movements for human interfaces using a flexible piezoelectric
      thin film sensor.
AB  - This paper proposes a novel method to measure muscle movements for human
      interfaces. During muscle movements, cross-sectional muscle area changes, and
      this can be detected at the skin surface. In this study, a flexible piezoelectric
      thin film sensor is used to measure the morphological change of the skin surface.
      This sensor is made of oriented aluminum nitride (AlN) thin film, and the total
      thickness is less than 40 mum. Since the AlN film sensor has good sensitivity,
      small strain of the skin surface can be measured. Furthermore, a motion
      classification method is developed to investigate the potential of the proposed
      sensor for its use in human interfaces. Response characteristics of the AlN
      sensor were tested with experiments using a cantilever beam. In addition, motion
      classification experiments were conducted with five subjects, including a patient
      with cervical spine injury. The experimental results validate the effectiveness
      of the proposed method.

PMID- 19162607
TI  - An instrument to measure the convective heat transfer coefficient on large
      vessels.
AB  - Hepatocellular carcinoma is one of the most common malignancies worldwide. During
      radiofrequency hepatic ablation, the tumor is heated by means of radiofrequency
      energy. The heating causes necrosis of the malignant tumor. Thus, if the
      procedure is successful it can cure the patient. Studies have shown that
      recurrences occur after the treatment and these recurrences frequently take place
      next to the hepatic artery and portal vein. The recurrences occur due to the high
      convective loss on these vessels. This work proposed, developed and tested an
      instrument for the measurement of the convective heat transfer coefficient (h) in
      large vessels. Moreover, this work developed a mechanical simulator and validated
      an equation developed by Consiglieri et al, which analytically determines the
      value of h. The instrument was tested using a mechanical simulator that
      reproduces the flow conditions and the geometry of large vessels in the liver. A
      flow velocity of 0.2 m/s was simulated in order to mock the typical flow at the
      portal vein. The average value of h using the experimental apparatus was 2130+/
      40 W.m(-2).K(-1) (mean+/-SD). The results showed that the error of the proposed
      method is approximately 22%. This work showed that the instrument can be used for
      measuring h in vitro and that the Consiglieri's equation can be used to determine
      the convective heat transfer coefficient on large vessels.

PMID- 19162608
TI  - In vivo tumor detection on rabbit with biopsy needle as MRE driver.
AB  - Magnetic Resonance Elastography (MRE) is a phase contrast imaging technique to
      quantitatively measure the elasticity of tissues. Typically, the oscillating
      driver is placed on the surface of objects to generate shear waves. When it is
      applied to detect tumors in deep location, the depth penetration of the wave is
      limited by attenuation and the biopsy procedure has to be performed separately.
      In this study, we describe a method using biopsy needle as the MRE driver to
      produce shear waves in tissues. We made comparison between the MRE acquisitions
      obtained with biopsy needle and surface drivers. Because the well-defined
      propagation wave pattern reduces the error in wavelength calculation, the
      acquisitions of biopsy needle driver shows better homogeneity in stiffness map.
      We also performed the experiment with the biopsy needle for in vivo tumor
      detection in rabbits. This study demonstrates that the biopsy needle driver is
      more effective than the surface driver for accurately measuring the stiffness and
      location of the tumor.

PMID- 19162609
TI  - How to track spermatozoa using high-speed visual feedback.
AB  - In this paper, we report how to track quickly and vigorously swimming ascidian
      spermatozoa using high-speed visual feedback at a frame rate of 1 kHz. Ascidian
      spermatozoa swim as fast as 300 microm/s by rotating their flagella 50 times/s.
      This vigorous swimming style has prevented stable image observation and made it
      difficult to track them reliably with our previously developed visual tracking
      system. Here, we describe how we overcame these problems using image processing
      techniques to achieve stable tracking of fast, small ascidian spermatozoa for
      more than 180 s using high-speed visual feedback.

PMID- 19162610
TI  - A miniature fully-passive microwave back-scattering device for short-range
      telemetry of neural potentials.
AB  - This paper describes a fully passive telemetry technique based on microwave
      backscattering. In this technique, a subharmonically-pumped passive mixer is
      coupled to a bio-probe and one or two miniature antennas. When interrogated by an
      RF excitation, this device generates an amplitude modulated RF backscattering
      component centered at twice the frequency of excitation. An external sensitive
      receiver can be used to demodulate the backscattering component and recover the
      bio-potential. A simple prototype based on solid state diodes has been fabricated
      and tested for 2.4/4.8 GHz and has the dimensions of 11.5x4.6 mm2 and thickness
      of approximately 1 mm. Experiments with this very simple device show that low
      frequency signals (fm<1 kHz) as low as 1 mV can results in double-sideband levels
      of greater than -126 dBm for an incident RF power of less than 1 mW/cm2. The
      proposed device is intended to be coated with an insulating bio-compatible
      coating and serve as a telemetry chip for chronic implantation inside the body.

PMID- 19162612
TI  - Experiment-specific models of ventricular electrical activation: construction and
      application.
AB  - Experimental intramural recordings of electrical activity at high resolution have
      been made in the in-vivo pig LV free wall. To analyze features of these
      recordings experiment-specific 3D computer models of tissue structures and
      electrical behavior around the recording sites were constructed. The construction
      of the models used novel tissue image registration, correction and feature
      extraction methods. Appropriate model conductivity parameters were deduced from
      measurements and used to replicate features of experimental recordings.

PMID- 19162611
TI  - Dynamic action potential clamp as a powerful tool in the development of a gene
      based bio-pacemaker.
AB  - The development of a genetically engineered 'biological pacemaker', or 'bio
      pacemaker', is a rapidly emerging field of research. One of the approaches in
      this field is to turn intrinsically quiescent myocardial cells, i.e., atrial or
      ventricular cells, into pacemaker cells by making them express the cardiac
      hyperpolarization-activated 'pacemaker current' If (known in neurophysiology as
      Ih), which is encoded by the hyperpolarization-activated cyclic nucleotide
      modulated (HCN) gene family. We carried out 'dynamic action potential clamp'
      (dAPC) experiments in which we record current from a HEK-293 cell transfected
      with HCN4, which is the dominant HCN isoform in the sinoatrial (SA) node. This
      HCN4-transfected HEK-293 cell is voltage-clamped by the action potential
      generated in a real-time simulation of a human atrial cell (Courtemanche-Ramirez
      Nattel model). In a continuous feedback loop, this current is injected into the
      atrial cell, so that this cell effectively expresses an HCN4-based pacemaker
      current. With sufficiently high 'expression levels' of HCN4 current the atrial
      cell is turned into a pacemaker cell with an SA nodal like action potential.
      Lower expression levels are sufficient if the inward rectifier potassium current
      (IK1), which is largely responsible for the stable resting potential of atrial
      cells, is 'down-regulated' by 50%, thus mimicking the gene therapy strategy to
      create a bio-pacemaker by down-regulation of IK1 and (over-)expression of If. Our
      dAPC experiments provide direct insights into the effects of introducing HCN4
      current into an atrial cell, illustrating that dynamic action potential clamp can
      be a powerful tool in the process of developing a gene-based bio-pacemaker.

PMID- 19162613
TI  - Regional differences in rabbit atrial action potential properties: mechanisms,
      consequences and pharmacological implications.
AB  - Regional differences in electrical action potential (AP) properties can provide a
      substrate for atrial arrhythmias. We quantify such differences by developing
      detailed AP models for the left (LA) and right (RA) rabbit atrial cells in order
      to study the underlying electrophysiological mechanisms, as well as their impacts
      on vulnerable properties of the atrial tissue. The transient outward current,
      Ito, is identified as the major factor contributing to the AP differences between
      the LA and RA cells, which suggests a potential pharmacological target for
      reducing heterogeneity and vulnerability of the atria.

PMID- 19162614
TI  - Structure specific models of electrical function in the right atrial appendage.
AB  - Atrial fibrillation is the most common cardiac arrhythmia. It is prevalent in the
      elderly and contributes to mortality in congestive heart failure. Computer models
      of atrial electrical activation that incorporate realistic structure provide a
      means of investigating the mechanisms that initiate and maintain reentrant atrial
      arrhythmia. We are extending computational and experimental techniques that are
      well established in our laboratory to develop a detailed structure-based model of
      atrial electrical function. The 3D geometry of the atria and veno-atrial
      junctions is reconstructed from magnetic resonance images and detailed structure
      from specific regions of the atria is acquired using a semi-automated extended
      volume imaging system. As an example of our approach, we present a reconstruction
      of the pig right atrial appendage (RAA), including the pectinate muscles (PM) and
      crista terminalis (CT). The RAA was embedded in wax and the block surface was
      serially etched, stained and imaged, then removed using an ultramiller to produce
      a uniformly-spaced image stack. Tissue was segmented and connected voxels were
      selected using a 3D region-growing algorithm to construct RAA geometry.
      Electrical activity has been modeled on this structure using the Courtemanche
      atrial cell activation model. A bidomain formulation was used employing a grid
      based finite element solver. The RAA was activated by applying a stimulus (150
      microA/mm3, 5 ms) to the 27 grid points at the top of the CT. Despite the complex
      structure of the PM, RAA activation was relatively uniform.

PMID- 19162615
TI  - Role of Purkinje system in cardiac arrhythmias.
AB  - The mechanisms responsible for postshock behavior of the heart are poorly
      understood. Below threshold shocks may induce arrhythmias that are difficult to
      contain. Cardiac vulnerability to shocks and defibrillation efficacy are largely
      determined by the postshock activity during the occurrence of a brief
      electrically quiescent period, known as the isoelectric window (IW) and
      activations following the IW period. This paper presents a detailed computer
      simulation study that underlines the role of the Purkinje system (PS) in
      postshock arrhythmogenesis. Reentry was induced in an anatomically realistic
      rabbit heart model using three different shocking protocols. Regions of
      vulnerability were determined for each protocol with and without PS. The role of
      PS during reentry was studied by isolating the PS from myocardium at various
      instances. The earliest post-shock activations were observed originating from the
      PS which initiated the reentry. The PS was shown to facilitate the reentry
      induction at weaker shocks. The PS also helped to stabilize the reentry in the
      early stages but did not play any significant role in the later stages. This
      research provides valuable insights into the postshock arrhythmogenesis and
      maintenance, and extends the discussion on the occurrence of IW as observed
      during clinical and experimental studies.

PMID- 19162617
TI  - Tracking single-trial evoked potential changes with Kalman filtering and
      smoothing.
AB  - A mathematical way to describe trial-to-trial variations in evoked potentials
      (EPs) is given by state-space modeling. Linear estimators optimal in the mean
      square sense can then be obtained through Kalman filter and smoother algorithms.
      Of importance are the parametrization of the problem and the selection of an
      observation model for estimation. In this paper, we introduce a general way for
      designing a model for dynamical estimation of EPs. The observation model is
      constructed based on a finite impulse response (FIR) filter and can be used for
      different kind of EPs. We also demonstrate that for batch processing the use of
      the smoother algorithm is preferable. The method is demonstrated with
      measurements obtained from an experiment with visual stimulation.

PMID- 19162616
TI  - A sensitive algorithm for automatic detection of space-time alternating signals
      in cardiac tissue.
AB  - Alternans, a beat-to-beat alternation in cardiac signals, may serve as a
      precursor to lethal cardiac arrhythmias, including ventricular tachycardia and
      ventricular fibrillation. Therefore, alternans is a desirable target of early
      arrhythmia prediction/detection. For long-term records and in the presence of
      noise, the definition of alternans is qualitative and ambiguous. This makes their
      automatic detection in large spatiotemporal data sets almost impossible. We
      present here a quantitative combinatorics-derived definition of alternans in the
      presence of random noise and a novel algorithm for automatic alternans detection
      using criteria like temporal persistence (TP), representative phase (RP) and
      alternans ratio (AR). This technique is validated by comparison to theoretically
      derived probabilities and by test data sets with white noise. Finally, the
      algorithm is applied to ultra-high resolution optical mapping data from cultured
      cell monolayers, exhibiting calcium alternans. Early fine-scale alternans, close
      to the noise level, were revealed and linked to the later formation of larger
      regions and evolution of spatially discordant alternans (SDA). This robust new
      technique can be useful in quantification and better understanding of the onset
      of arrhythmias and in general analysis of space-time alternating signals.

PMID- 19162618
TI  - Dynamic analysis of Probabilistic Boolean Network for fMRI study in Parkinson's
      disease.
AB  - Probabilistic Boolean Networks (PBNs) have recently been applied to infer
      functional connectivity between brain regions of interested (ROIs), and to
      identify the existence of connectivity abnormality in Parkinson's Disease (PD).
      In addition to PBNs' promising application in inferring significant brain
      connections, PBN modeling for brain ROIs also enables researchers to study
      dynamic activities of the system under stochastic condition, gaining essential
      information regarding asymptotic behaviors of ROIs for potential therapeutic
      intervention in PD. In this paper, we will present a PBN model for fMRI analysis
      and study its asymptotic behavior. The PBN results indicate significant
      differences in asymptotic behaviors between PD patients and normal subjects.
      Hypothesizing the observed feature states for normal subject as the desired
      functional states, we further explore possible methods to manipulate the
      dynamical network behavior of PD patients in the favor of the desired states from
      the view of random perturbation as well as intervention.

PMID- 19162619
TI  - Modelling temporal evolution of cardiac electrophysiological features using
      Hidden Semi-Markov Models.
AB  - This paper presents a new method to analyse cardiac electrophysiological
      dynamics. It aims to classify or to cluster (i.e. to find natural groups)
      patients according to the dynamics of features extracted from their ECG. In this
      work, the dynamics of the features are modelled with Continuous Density Hidden
      Semi-Markovian Models (CDHSMM) which are interesting for the characterization of
      continuous multivariate time series without a priori information. These models
      can be easily used for classification and clustering. In this last case, a
      specific method, based on a fuzzy Expectation Maximisation (EM) algorithm, is
      proposed. Both tasks are applied to the analysis of ischemic episodes with
      encouraging results and a classification accuracy of 71%.

PMID- 19162620
TI  - EEG analysis using moving average-type neural network.
AB  - The brain is one of nonlinear systems. EEG (electroencephalogram) is widely used
      to monitor the brain condition. Frequency analysis method is given as general EEG
      analysis method. DR analysis is to evaluate the deviation ratio of power spectrum
      of arbitrary frequency band. On the other hand, neural networks are used to
      analyze nonlinear systems because of their ability to capture the dynamics of
      complex system. In this study, we propose the application of moving average-type
      neural networks (MANN) to analyze the EEG and compare the result of MANN analysis
      with the one of DR analysis. In this time, we used the randomness to optimize the
      number of input units of MANNs. In MANN analysis method, the measured EEG is
      divided into overlapped period 20 seconds. A MANN is trained to predict the EEG
      using three previous samples in each period. After training, the connecting
      weights of each MANN are compared using the inner product to evaluate changes in
      brain condition. We used measured EEG in closing/opening eyes to analyze.
      According to the results, the usefulness of MANN analysis was confirmed. And MANN
      analysis has possibility to be able to apply to analysis of the other EEG data or
      the other nonlinear systems.

PMID- 19162621
TI  - Comparison of adaptive features with linear discriminant classifier for Brain
      computer Interfaces.
AB  - Many Brain-computer Interfaces (BCI) use band-power estimates with more or less
      subject-specific optimization of the frequency bands. However, a number of
      alternative EEG features do not need to select the frequency bands; estimators
      for these features have been modified for an adaptive use. The popular band power
      estimates were compared with Adaptive AutoRegressive parameters, Hjorth, Barlow,
      Wackermann, Brain-Rate and a new feature type called Time Domain Parameter. The
      results from 21 subjects show that several features provide an equally good or
      even better performance, while no subject-specific optimization is needed, and
      they are also preferable to band power when the most discriminating frequency
      band of a subject is not known.

PMID- 19162622
TI  - Detection of atrial fibrillation episodes using SVM.
AB  - This paper explains an atrial fibrillation (AF) detection algorithm, which
      consists of a linear discriminant analysis (LDA) based feature reduction scheme
      and a support vector machine (SVM) based classifier. Initially nine features were
      extracted from the input episodes each containing 32 RR intervals by linear and
      nonlinear methods. Next, to improve the learning efficiency of the classifier and
      to reduce the learning time, these features are reduced to 4 features by LDA. The
      performance of the proposed method in discriminating AF episodes was evaluated
      using MIT-BIH arrhythmia database. The obtained sensitivity, specificity and
      positive predictivity were 99.07%, 100% and 100%, respectively.

PMID- 19162623
TI  - Quantitative evaluation of movement disorders in neurological diseases based on
      EMG signals.
AB  - In this paper, we propose a new method to make a quantitative evaluation for
      movement disorders. Based on the EMG signals, we analyzed the movement disorders
      for cerebellar patients at the motor command level. As an experimental task, we
      asked subjects to perform step-tracking wrist movements with a manipulandum, and
      simultaneously recorded wrist joint movements and muscle activities of four wrist
      prime movers with surface electrodes. In order to quantitatively evaluate the
      correspondence between the movement kinematics and the activities of the four
      muscles, we approximated the relationship between the wrist joint torque
      calculated from the kinematics and the four EMG signals using a dynamics model of
      wrist joint. Our surprising observation was that there was very high correlation
      between the wrist joint torque and the EMG signals. In fact, we identified causal
      abnormality of muscle activities for movement disorders of cerebellar patients,
      confirming effectiveness of our proposed method for analysis of movement
      disorders at the level of the motor command.

PMID- 19162624
TI  - An embedded controller for a 7-degree of freedom prosthetic arm.
AB  - We present results from an embedded real-time hardware system capable of decoding
      surface myoelectric signals (sMES) to control a seven degree of freedom upper
      limb prosthesis. This is one of the first hardware implementations of sMES
      decoding algorithms and the most advanced controller to-date. We compare decoding
      results from the device to simulation results from a real-time PC-based operating
      system. Performance of both systems is shown to be similar, with decoding
      accuracy greater than 90% for the floating point software simulation and 80% for
      fixed point hardware and software implementations.

PMID- 19162625
TI  - Study of stroke condition and hand dominance using a hidden Markov, multivariate
      autoregressive (HMM-mAR) network framework.
AB  - To investigate the effects of stroke and hand dominance on muscle association
      patterns during reaching movements, we applied the hidden Markov model,
      multivariate autoregressive (HMM-mAR) framework to real sEMG recordings from
      healthy and stroke subjects performing reaching tasks. Statistical analysis is
      performed to construct subject- and group-level muscle connectivity networks.
      Associating structural features are extracted for subsequent classification of
      reaching movements. The HMM-mAR framework is shown to be able to consistently
      segments each reaching movement into the initial phase and the full-movement
      phase. The inferred muscle networks illustrate that healthy and stroke subjects
      use distinguishably different muscle synergies during the initial phase. The
      classification results further confirm that structural features extracted from
      the initial phase are useful in classifying subjects with differing stroke
      condition and handedness.

PMID- 19162626
TI  - Decoding individuated finger flexions with Implantable MyoElectric Sensors.
AB  - We trained a rhesus monkey to perform randomly cued, individuated finger flexions
      of the thumb, index, and middle finger. Nine Implantable MyoElectric Sensors
      (IMES) were then surgically implanted into the finger muscles of the monkey's
      forearm, without any observable adverse chronic effects. Using an inductive link,
      we wirelessly recorded EMG from the IMES as the monkey performed a finger flexion
      task. A principal components analysis (PCA) based algorithm was used to decode
      which finger switch was pressed based on the recorded EMG. This algorithm
      correctly decoded which finger was moved 89% of the time. These results
      demonstrate that IMES offer a safe and highly promising approach for providing
      intuitive, dexterous control of artificial limbs and hands after amputation.

PMID- 19162627
TI  - Continuous decoding of finger position from surface EMG signals for the control
      of powered prostheses.
AB  - As development toward multi-fingered dexterous prosthetic hands continues, there
      is a growing need for more flexible and intuitive control schemes. Through the
      use of generalized electrode placement and well-established methods of pattern
      recognition, we have developed a basis for asynchronous decoding of finger
      positions. With the present method, correlations as large as 0.91 and mean
      overall decoding errors of approximately 11% have been achieved with average
      decoding errors of between decoded and actual conformation of the
      metacarpophalangeal joints of individual fingers. It is hoped that these results
      will serve as a foundation from which to encourage further investigation into
      more intuitive methods of myoelectric control of powered upper limb prostheses.

PMID- 19162628
TI  - Predicting EMG with generalized Volterra kernel model.
AB  - Generalized Volterra kernel model (GVM) is developed in spirits of the
      generalized linear model (GLM) and used to predict EMG signals based on M1
      cortical spike trains during a prehension task. The GVM for EMG consists of a
      cascade of a multiple-input-single-output Volterra kernel model (VM) and an
      exponential activation function. Without loss of generality, the exponential
      activation function constrains the unbounded VM output within the positive range,
      which fully covers the dynamic range of the rectified EMG signals. Results show
      that GVMs are more accurate than the VMs due to this asymptotic property.

PMID- 19162629
TI  - A new variational technique for combining affine registration and optical flow in
      echocardiography images.
AB  - Since myocardial motion is directly related to cardiac vascular supply, it can be
      helpful in diagnosing the heart abnormalities. The most comprehensive and
      available imaging study of the cardiac function is B-Mode echocardiography.
      However diagnostic systems are expert dependent and motion is not clear in the B
      mode echocardiography images and therefore many efforts are pointed toward
      proposing new methods to measure the motion accurately. So far there have been
      many methods for myocardial motion estimation such as affine registration,
      elastic registration or optical flow but each method suffers from lack of
      accuracy. To increase the accuracy of motion detection techniques, we propose a
      new algorithm based on a variational technique to combine the efficiencies of
      optical flow methods and affine registration in combination with multi-resolution
      spatiotemporal Spline moments. The evaluation was performed on simulated,
      synthetic and real data. A comparison between the proposed method and several
      other methods shows its better performance to measure the motion more accurately
      in the presence of shear, rotation and noise. The proposed method achieved
      rotational error of 2.6 degrees per frame and amplitude error of 3.7 percent per
      frame. These results demonstrate a better efficiency with respect to other B-Mode
      echocardiography motion estimation techniques such as Lucas-Kanade, Horn-Schunck
      and spatiotemporal affine technique.

PMID- 19162630
TI  - Functional bull's eye based on three dimensional velocity information to quantify
      left ventricle motion in gated-SPECT.
AB  - The description and quantification of the regional function of the cardiac left
      ventricle (LV) involve making quantitative measurements of the heart movement. In
      this work we present a functional bull's eye or polar map that depicts three
      dimensional coded velocity information from gated-SPECT images. The polar map is
      built based on the standards defined by the AHA and comprises 17 segments. The
      use of the proposed map was tested in images from 5 normal subjects and 4
      patients with intraventricular dyssynchrony submitted to cardiac
      resynchronization therapy. Preliminary results have shown good indications of
      potential application of the technique to the diagnosis and the follow up of such
      patients. The functional polar map is independent of the heart size, so it makes
      possible the creation of normal pattern standards. Such standards would allow the
      application of the method in a broad range of applications involving the analysis
      of the heart movement.

PMID- 19162631
TI  - 3D left ventricular segmentation using double active contours and double active
      surfaces.
AB  - We propose a 3D left ventricular segmentation method for cardiac MR images. There
      are two steps in our method. In the first step, we improve our double active
      contours for segmenting the endocardial and the epicardial boundaries
      simultaneously without requiring any training sets. In the second step, we
      designed a double active surface method to segment the volume within the
      endocardium and the thickness of the myocardium simultaneously from a set of 2D
      contours generated from the first step. Our results show successful simultaneous
      segmentation of the 3D left ventricular model of the heart.

PMID- 19162632
TI  - Semi-automatic detection of the left ventricular border.
AB  - Two semi-automatic methods for the detection of the left ventricular border in
      two-dimensional short axis echocardiographic images are presented and compared.
      In these methods, the left ventricular area variation curve is calculated during
      a complete cardiac cycle after the segmentation of several frames. This allows
      the evaluation of the cardiovascular dynamics and the identification of important
      clinical parameters. The algorithms are proposed as several independent modules.
      The results are validated through the comparison between the semi-automatic
      continuous boundaries and manuals boundaries sketched by a medical specialist.

PMID- 19162633
TI  - Left ventricle segmentation in echocardiography using a radial-search-based image
      processing algorithm.
AB  - A new left ventricle segmentation method in two-dimensional echocardiography
      images is proposed. Image processing techniques combined with radial search and
      temporal information are used to extract the left ventricle boundary. Borders
      from sequential images are extracted using the proposed method, and a curve
      illustrating the area variation within a cardiac cycle is presented. Performance
      evaluation is performed by comparing the borders obtained from the presented
      method to those manually prescribed by a medical specialist. The new sequential
      radial search algorithm improved the border extraction from long-axis ultrasound
      images, specially the ones where the mitral valve was open. Segmentation errors
      due to low contrast were corrected.

PMID- 19162634
TI  - Virtual sectioning of cardiac tissue relative to fiber orientation.
AB  - Ventricular myocardium is composed of muscle fibers organised into a complex,
      branching, laminar (sheet-like) structure. The fibers run approximately parallel
      to the epicardial wall, but their orientation relative to the circumferential
      axis varies transmurally, rotating from around -70 degrees at the epicardium to
      +70 degrees at the endocardium. This ensures that any flat transmural imaging
      plane or histological section contains only a partial description of myocardial
      architecture, as fibers intersect with the image plane at a variety of angles
      depending on transmural depth. We have developed a new way of viewing
      microstructure that accounts for this variation. Extended-volume confocal 3-D
      images of normal rat left-ventricular wall have previously been acquired, with an
      approximate size of 4x1x1 mm3. The transmural fiber rotation is measured on
      planes parallel to the epicardium, and used to define a curvilinear coordinate
      system with a transmural axis, and a second axis defined relative to the local
      fiber orientation. Images extracted from the image volume on curvilinear planes
      derived from these axes reveal a consistent view of myocardial architecture.

PMID- 19162635
TI  - Temperature-dependent dielectric properties of liver tissue measured during
      thermal ablation: toward an improved numerical model.
AB  - The development of microwave tumor ablation devices depends largely on numerical
      simulations of antenna characteristics and transient electromagnetic heating.
      However, without an adequate tissue model simulation predictions can vary widely
      from experimental results. In this study, tissue dielectric properties are
      measured to capture changes induced by temperature, cellular makeup and water
      content during thermal ablation. Measurements made using this technique agree
      closely with previous measurements for temperatures up to 50 degrees C, but both
      relative permittivity and conductivity decrease by as much as 50 percent when
      temperatures approach 100 degrees C.

PMID- 19162636
TI  - Heating properties of re-entrant resonant cavity applicator for brain tumor with
      simple head model.
AB  - We have already confirmed the effectiveness of the re-entrant resonant cavity
      applicator system with non-invasive experiments of heating cylindrical agar
      phantoms and computer simulations. This paper discusses the heating properties of
      the developed heating system with a human head model made of agar for brain tumor
      hyperthermia treatment. First, we present the results of heating a uniform agar
      head model with the developed heating system. In the experiments, the temperature
      rise at the center of the agar was about 8 degrees C, it was found that the
      center of the agar is heated to maximum temperature non-invasively. Second, we
      present the results of heating a non-uniform agar head model having an oral
      cavity and a nasal cavity. We found that the center of the agar can be heated to
      maximum temperature as well as uniform agar head model. From these results, it is
      confirmed that the possibility of effective hyperthermia for various types of
      deep-seated brain tumors.

PMID- 19162637
TI  - Tumor ablation at low frequencies for preferential tumor heating: initial ex-vivo
      tissue studies.
AB  - PURPOSE: Radiofrequency (RF) ablation is a common treatment modality for
      inoperable liver cancer. Several studies have demonstrated that significant
      differences exist between the electrical properties of tumor and normal tissue,
      especially at lower frequencies. In this study, we investigated in an ex vivo
      setting whether the use of lower frequencies during ablation results in
      preferential heating of tumor tissue. MATERIALS AND METHODS: We created a setup
      consisting of adjacent layers (3 cm thick each) of tumor phantom (agar gel) and
      freshly excised normal porcine liver tissue in a saline bath. A standard RF
      needle electrode was placed such that half of the active electrode was in each
      layer. We applied 25 W of power at a frequency of either 20 or 325 kHz to the
      electrode for 12 minutes. Temperatures were recorded 6 and 10 mm from the
      electrode in both the phantom and normal tissue layers. RESULTS: The ratio of the
      temperature rise in the tumor phantom to the temperature rise in the normal
      tissue was significantly higher in the 20 kHz trials after 12 minutes at both 6
      mm (1.50+/-0.27 vs. 1.02+/-0.16) and 10 mm (1.34+/-0.28 vs. 0.90+/-0.11) from the
      electrode (p<0.01). CONCLUSION: Tumor ablation at frequencies lower than
      currently used may preferentially heat tumor tissue, preserving normal tissue at
      the treatment site.

PMID- 19162638
TI  - Finite element model of wet brush RF ablation catheter.
AB  - We proposed a novel design of irrigated wet brush ablation electrode that is
      flexible and efficiently cooled for RF catheter ablation. We described the FEM
      method to analyze lesion and temperature distribution during ablation. The
      analysis demonstrated that this brush electrode is capable of creating lesions up
      to 10 mm deep. The ablation electrode is maintained at lower temperature by the
      irrigation and lesion is much deeper than non-irrigated ablation electrode. The
      results also suggested that the electrical conductivity of the material is more
      critical than thermal conductivity to lesion creation. The optimal electrical
      conductivity for the brush material should larger than 1 mS/mm.

PMID- 19162639
TI  - Surgical Cardiac Ablation devices: numerical model study.
AB  - Numerical Finite Element Method models were used to compare and contrast bipolar
      and monopolar RF electrode geometries used for open chest surgical Cardiac
      Ablation in a modified Maze procedure. The models included electrical, thermal
      and cardiac muscle damage fields with irreversible thermal alteration in the form
      of loss of native state birefringence in cardiac muscle as the standard of
      comparison. Kinetic rate coefficients for these models were: A=2.94x10(39) (1/s)
      and E=2.596x10(5) (J/mole), from literature. Model results show the spatial
      development of thermal damage relative to the transient thermal field. Numerical
      methods may be used to compare and contrast transient temperature field histories
      and damage extent in the RF electrode design process.

PMID- 19162640
TI  - A novel highly articulated robotic surgical system for epicardial ablation.
AB  - We have developed a novel, highly articulated robotic surgical system to enable
      minimally invasive intrapericardial interventions through a subxiphoid approach
      and have performed preliminary tests of epicardial left atrial ablation in
      porcine (N=3) and human cadaver (N=2) preparations. In this study, the novel
      highly articulated robotic surgical system successfully provided safe epicardial
      ablations to the left atrium in porcine beating heart models via a subxiphoid
      approach. We have also performed complex guidance of the robot and subsequent
      ablation in a cadaveric preparation for successful pulmonary vein isolation.

PMID- 19162641
TI  - A real-time maximum-likelihood heart-rate estimator for wearable textile sensors.
AB  - This paper presents a real-time maximum-likelihood heart-rate estimator for ECG
      data measured via wearable textile sensors. The ECG signals measured from
      wearable dry electrodes are notorious for its susceptibility to interference from
      the respiration or the motion of wearing person such that the signal quality may
      degrade dramatically. To overcome these obstacles, in the proposed heart-rate
      estimator we first employ the subspace approach to remove the wandering baseline,
      then use a simple nonlinear absolute operation to reduce the high-frequency noise
      contamination, and finally apply the maximum likelihood estimation technique for
      estimating the interval of R-R peaks. A parameter derived from the byproduct of
      maximum likelihood estimation is also proposed as an indicator for signal
      quality. To achieve the goal of real-time, we develop a simple adaptive algorithm
      from the numerical power method to realize the subspace filter and apply the fast
      Fourier transform (FFT) technique for realization of the correlation technique
      such that the whole estimator can be implemented in an FPGA system. Experiments
      are performed to demonstrate the viability of the proposed system.

PMID- 19162642
TI  - Performance analysis of approximate Affine Projection Algorithm in acoustic
      feedback cancellation.
AB  - Acoustic feedback is an annoying problem in several audio applications and
      especially in hearing aids. Adaptive feedback cancellation techniques have
      attracted recent attention and show great promise in reducing the deleterious
      effects of feedback. In this paper, we investigated the performance of a class of
      adaptive feedback cancellation algorithms viz. the approximated Affine Projection
      Algorithms (APA). Mixed results were obtained with the natural speech and music
      data collected from five different commercial hearing aids in a variety of sub
      oscillatory and oscillatory feedback conditions. The performance of the
      approximated APA was significantly better with music stimuli than natural speech
      stimuli.

PMID- 19162643
TI  - Neural network based EEG denoising.
AB  - A novel filter is proposed by applying back propagation neural network (BPNN)
      ensemble where the noisy signal and the reference one are the same in a learning
      process. This neural network (NN) ensemble filter not only well reduces additive
      and multiplicative white noise inside signals, but also preserves signals'
      characteristics. It is proved that the reduction of noise using NN ensemble
      filter is better than the improved epsilon nonlinear filter and single NN filter
      while signal to noise ratio is smaller. The performance of the NN ensemble filter
      is demonstrated in computer simulations and actual electroencephalogram (EEG)
      signals processing.

PMID- 19162644
TI  - Comparison between hybrid feedforward-feedback, feedforward, and feedback
      structures for active noise control of fMRI noise.
AB  - The performance of FIR feedforward, IIR feedforward, FIR feedback, hybrid FIR
      feedforward--FIR feedback, and hybrid IIR feedforward - FIR feedback structures
      for active noise control (ANC) are compared for an fMRI noise application. The
      filtered-input normalized least squares (FxNLMS) algorithm is used to update the
      coefficients of the adaptive filters in all these structures. Realistic primary
      and secondary paths of an fMRI bore are used by estimating them on a half
      cylindrical acrylic bore of 0.76 m (D)x1.52 m (L). Detailed results of the
      performance of the ANC system are presented in the paper for each of these
      structures. We find that the IIR feedforward structure produces most of the
      performance improvement in the hybrid IIR feedforward - FIR feedback structure
      and adding the feedback structure becomes almost redundant in the case of fMRI
      noise.

PMID- 19162645
TI  - A new noise reduction method for oscillometric blood pressure measurement.
AB  - In this paper, a new noise reduction method was proposed for oscillometric blood
      pressure measurement. The proposed method uses a capacitive sensor and an
      adaptive filter to minimize blood pressure measurement error. Noise such as
      undesired external pressure applied to cuff was focused on. Three types of the
      distorted oscillation signals (no overlap, non-consecutive overlap, consecutive
      overlap between the noise and the oscillation) were used to compare the
      conventional method using linear interpolation and the proposed method using the
      adaptive filter. The proposed method outperformed the conventional method in the
      case of consecutive overlap between the noise and the oscillation. The proposed
      method could be useful for measuring blood pressure in such a noisy environment
      that the subject is being transported.

PMID- 19162646
TI  - Adaptive impulse correlated filter (AICF) improvement for photoplethysmographic
      signals.
AB  - Measured PPG signals are often contaminated with different noises and artifacts.
      For clinical diagnostics, it is important to have accurate signals. Removing
      noises and motion artifacts from PPG signal has been actual also in previous
      studies. In this study, we are proposing new adaptive impulse correlated filter
      (AICF) improvement for plethysmographic signals. It uses ECG signal to create
      reference with unit impulses. All signals, which do not correlate with reference
      signal, will be filtered out. To show, how the filter acts with artifacts with
      low SNR, the experiment was conducted.

PMID- 19162647
TI  - Instantaneous heart rate: should RR-intervals be resampled?
AB  - RR-interval sequences (tachograms) represent heart rate variability discretely.
      When time series representations of instantaneous heart rate (IHR) are required,
      tachograms are often resampled into a time series. This paper demonstrates that
      traditional RR-interval resampling is often inconsistent with the time domain
      constraints of the tachogram. A general technique, called frequency-modulated
      phase-interpolation (FMPI), is presented that preserves the time domain
      constraints. Results of FMPI in the synthesis of ECG signals with accurate event
      interval reconstruction are shown. Discussion of the model against IPFM and the
      heart timing signal is presented. Consequences of the IHR reconstruction
      perspective to the spectral characterization of heart rate variability are also
      introduced.

PMID- 19162648
TI  - Template-based compression of ECG signals.
AB  - A new approach for ECG data compression is proposed in this paper. Using a
      nonlinear least squares optimization procedure, the approach employs an algorithm
      based on template model fitting. Only 12 parameters are required to fully
      represent the ECG signal without diagnostic information loss. The effectiveness
      of our ECG compression technique is described in terms of high compression
      ratios, relatively low distortion values of less than 9%, and a low computational
      cost, thus demonstrating the beneficial use of our technique for ECG data storage
      and online transmission. Comparisons with other recent compression methods in the
      literature have shown that our method performs better.

PMID- 19162649
TI  - Frequency distribution effects of anchored mother rotors--a computer model study.
AB  - Recent findings indicate that major organized centers (mother rotors) can
      maintain ventricular fibrillation (VF). In computer models the mother rotors can
      be induced by local shortening of the action potential duration (APD) in the
      cardiac tissue. Because of the fact that these rotors tend to drift away towards
      regions with longer APD, an additional heterogeneity (e.g. bundle) has to be
      included in the model for stabilizing the activation. Thus, the rotor anchors on
      this bundle and yields to interesting frequency distribution effects. In the
      dominant frequency (DF) map of a simplified computer model of the left ventricle
      it can be observed that the anchoring site of the rotor produces a slightly lower
      DF than in the surrounding cardiac tissue. That means that due to the load effect
      of the bundle the frequency is decreased. Furthermore the meandering of the
      mother rotor around this anchor site is reflected in the spectra of signals taken
      randomly in the organized region. These effects are both detected with two
      different independent spectral estimators with different resolutions.

PMID- 19162650
TI  - Short-term diabetes blood glucose prediction based on blood glucose measurements.
AB  - Insulin Dependent Diabetes Mellitus (IDDM) is a chronic disease characterized by
      the inability of the pancreas to produce sufficient amounts of insulin. Daily
      compensation of the deficiency requires 4-6 insulin injections to be taken daily,
      the aim of this insulin therapy being to maintain normoglycemia--i.e., a blood
      glucose level between 4-7 mmol/L. To determine the quantity and timing of these
      injections, various different approaches are used. Currently, mostly qualitative
      and semi-quantitative models and reasoning are used to design such a therapy.
      Here, an attempt is made to show how system identification and control may be
      used to estimate predictive quantitative models to be used in design of optimal
      insulin regimens. The system was divided into three subsystems, the insulin
      subsystem, the glucose subsystem and the insulin-glucose interaction. The insulin
      subsystem aims to describe the absorbtion of injected insulin from the
      subcutaneous depots and the glucose subsystem the absorbtion of glucose from the
      gut following a meal. These subsystems were modeled using compartment models and
      proposed models found in the literature. Several black-box models and grey-box
      models describing the insulin/glucose interaction were developed and analysed.
      These models were fitted to real data monitored by a IDDM patient. Many
      difficulties were encountered, typical of biomedical systems: Non-uniform and
      scarce sampling, time-varying dynamics and severe nonlinearities were some of the
      difficulties encountered during the modeling. None of the proposed models were
      able to describe the system accurately in all aspects during all conditions.
      However, all the linear models shared some dynamics. Based on the estimated
      models, short-term blood glucose predictors for up to two-hour-ahead blood
      glucose prediction were investigated.

PMID- 19162651
TI  - System identification of biomedical systems from short transients using space
      methods.
AB  - System identification technology has been a popular tool to analysis the dynamic
      behavior of biomedical systems. A segment of data with enough information must be
      collected in order to obtain unbiased estimate of the systems. However, some
      biomedical systems have short transients, such as Vestibulo-Ocular Reflex (VOR).
      Systems often cannot be identified from the short transients collected in one
      experiment. Thus, the experiments must be repeated, and an ensemble of input and
      output recorded. This paper presents a subspace method to identify Multiple Input
      and Multiple Output (MIMO) state space models for biomedical systems from short
      transients using ensemble data. A simulating ankle joint stiffness experiment
      demonstrates that the algorithm provides accurate results.

PMID- 19162652
TI  - Estimation of single-trial fMRI BOLD responses using combined EEG and fMRI
      measurements.
AB  - In this paper, we present a method for modeling human brain response using
      combined fMRI and EEG measurements. A subspace is formed using the eigenvectors
      of data correlation matrix of augmented measurements. This subspace is then used
      for regularization of the fitting of parametric model to fMRI BOLD signal. The
      approach is utilized for single-trial estimation of blood oxygenation level
      dependent (BOLD) responses in fMRI time series.

PMID- 19162653
TI  - Oscillometric blood pressure monitor modeling.
AB  - Oscillometric blood pressure monitors are fairly reliable medical equipment,
      inexpensive and widely used both in domicile and clinical measurements of blood
      pressure, however they have not yet been subject of deep investigation. The
      research reported in this paper presents the development of an analytical model
      of an oscillometric blood pressure monitor, a task which has not been dealt with
      and is useful in order to improve these devices' accuracy limitations. The
      approach taken was to divide the transducer in two distinct components, the
      electromechanical and the pneumatic, considering compression and decompression
      phases. Differential equations were derived, using electric and mechanical
      principles, to explain the equipment's behavior during the air-pump compression,
      and the pressure evolution during decompression was identified by exponential
      approximation. This comprehensive study obtained several non-ideal and nonlinear
      dynamics, and describes some of the possible simplifications to the models used.

PMID- 19162654
TI  - Respiratory parameter estimation in linear lung models.
AB  - If the respiratory system is represented as a one compartment model composed of
      linear electrical elements, the Minimum Variance Unbiased Estimation (MVUE) is
      the optimum statistical method to estimate the model parameters. Two well known
      linear models, RIC and Viscoelastic models were chosen and their parameters were
      estimated by MVUE. Synthetic data simulations showed that minimum 100 Hz sampling
      rate is required in order to have minimum variance. Estimation of lung inertance
      and viscoelastic tissue compliance parameters resulted in very large estimation
      variance, whereas the rest of the parameters were estimated successfully. Both
      parameter values and estimator variances have their own characterization in terms
      of patient discrimination for diagnostic purposes.

PMID- 19162655
TI  - Oscillation and its inhibition in a neuronal network model for tinnitus sound
      therapy.
AB  - Tinnitus is the perception of phantom sounds in the ears or in the head. Sound
      therapy techniques for tinnitus treatment have been proposed. In order to
      investigate mechanisms of tinnitus generation and the clinical effects of sound
      therapy from the viewpoint of neural engineering, we have proposed a
      computational model using a neural oscillator. In the present paper, we propose
      another model that is composed of model neurons described by simplified Hodgkin
      Huxley equations. By computer simulation it was detected that this model also has
      a bistable state, i.e., a stable oscillatory state and a stable equilibrium (non
      oscillatory) state coexist at a certain parameter region. It was also noticed
      that the oscillation can be inhibited by supplying constant or pulse train
      stimuli, which is hypothesized as an afferent signal that is employed as an
      acoustical signal for tinnitus treatment. By hypothesizing that the oscillation
      and the equilibrium correspond to generation and inhibition of tinnitus,
      respectively, these phenomena could explain the fact that the habituated human
      auditory system temporarily halts perception of tinnitus following sound therapy.

PMID- 19162656
TI  - Manifestation of fatigue in myoelectric signals of dynamic contractions produced
      during playing PC games.
AB  - This paper investigates manifestation of fatigue in myoelectric signals during
      dynamic contractions produced whilst playing PC games. The hand's myoelectric
      signals were collected in 26 independent sessions with 10 subjects. Two methods,
      spectral analysis and time-scale analysis, were applied to compute signal
      frequency and least-square linear regression was used to model the trend of
      frequency shift. Non-parametric statistical methods were employed to analyze
      experimental results, which indicates significant decline in signal frequency as
      a manifestation of fatigue in long-term muscle activities.

PMID- 19162657
TI  - Multiple models oscillometric blood pressure monitor identification.
AB  - Oscillometric blood pressure monitors are fairly reliable medical equipment,
      inexpensive and widely used both in domicile and clinical measurements of blood
      pressure, however they have not yet been subject of deep investigation. The
      research reported in this paper presents some a priori knowledge to build a model
      of an oscillometric blood pressure monitor and the results of the system
      identification, in order to help in the search for improvements in these devices'
      measurement accuracy. From several studies it is known that the cuff expansion,
      the compressible fluid flow and the electromechanical components of the system
      originate nonlinearities in the system dynamics. During the identification
      procedures it was seen that a multiple model approach was required in order to
      obtain a reliable representation in all the pressure range. The study of numerous
      parametric linear models and interpolation functions allowed the reduction of
      prediction errors, resulting in a final model with good quality results but with
      room to improvements in the transient response.

PMID- 19162658
TI  - System identification of mechanomyogram evoked by common peroneal nerve
      stimulation.
AB  - In the quantitative assessment of a system, a description of the low-order
      transfer function model is important. The objective of this study was to identify
      the system of a mechanomyogram (MMG) with SubSpace-based State Space model
      IDentification (4SID). The input data consisted of the electrical stimulation of
      the common peroneal nerve, which made the anterior tibial muscle contract. The
      output data consisted of the evoked MMG. We applied Fourier transform to the MMG
      signal and obtained a power spectrum. The 10th-order model was estimated by the
      4SID method. It was suggested that the frequency band separation of the power
      spectrum reflected the types of recruited muscle fiber. The results suggest that
      the MMG is a linear system which can be estimated in the lower-order transfer
      function model by applying the 4SID to each frequency band.

PMID- 19162659
TI  - Identifying changes in human skin electrical properties due to long-term
      NeuroMuscular Electrical Stimulation.
AB  - The skin electrical properties are identified using a standard NeuroMuscular
      Electrical Stimulation (NMES) voltage pulse. The three component series
      equivalent electrical model was chosen to account for the skin electrical
      properties. The values of each of these three electrical components of the
      equivalent electrical model were identified and compared throughout 40 minute
      daily NMES sessions and over 5 days. Current measurements were performed during
      the NMES sessions in a non-invasive way, in order to assess changes occuring
      during each stimulation session and due to long-term NMES.

PMID- 19162660
TI  - Design of lower limb prosthesis with contact pressure adjustment by MR fluid.
AB  - This paper reports on the development of a new lower limb prosthesis that can
      change its volume and hardness based on the users requirements. The size and
      viscosity of several Magneto-Rheological fluid filled bags, fixed on the inner
      side of the socket is changed, in order to vary the socket properties. TSB (total
      surface bearing) sockets have been most selling ones during these two decades.
      From the user's point of view, it is excellent in this type of sockets that the
      weight of user is supported with the entire socket surface. However, it is
      impossible to cope with the volume change of the user's stump. Experimental
      results show that the performance of the developed MR socket is better than the
      conventional TSB sockets because the MR socket is controllable in the size and
      viscosity.

PMID- 19162661
TI  - Automatic segmentation of the second cardiac sound by using wavelets and hidden
      Markov models.
AB  - This paper is concerned with the segmentation of the second heart sound (S2) of
      the phonocardiogram (PCG), in its two acoustic events, aortic (A2) and pulmonary
      (P2) components. The aortic valve (A2) usually closes before the pulmonary valve
      (P2) and the delay between these two events is known as 'split' and is typically
      less than 30 miliseconds. S2 splitting, reverse splitting or reverse occurrence
      of components A2 and P2 are the most important aspects regarding cardiac
      diagnosis carried out by the analysis of S2 cardiac sound. An automatic
      technique, based on discrete wavelet transform and hidden Markov models, is
      proposed in this paper to segment S2, to estimate de order of occurrence of A2
      and P2 and finally to estimate the delay between these two components (split). A
      discrete density hidden Markov model (DDHMM) is used for phonocardiogram
      segmentation while embedded continuous density hidden Markov models are used for
      acoustic models, which allows segmenting S2. Experimental results were evaluated
      on data collected from five different subjects, using CardioLab system and a Dash
      family patient monitor. The ECG leads I, II and III and an electronic stethoscope
      signal were sampled at 977 samples per second.

PMID- 19162663
TI  - Zerocrossing-based fine structure representation to convey Mandarin tonal
      information: a study on the noise effect.
AB  - Since the fine structure cue of the speech signal has been believed to be
      important for the pitch perception of cochlear implant (CI) users, studies are
      actively ongoing with attempts to propose novel CI speech processing strategies
      incorporating the fine structure cue. A speech synthesis model with the
      zerocrossing-based fine structure representation has been recently developed.
      This paper further examines its ability to convey Mandarin tonal information in
      the noisy conditions. Acoustic simulation experiment of Mandarin tone
      identification was conducted. The experimental results supported that the
      zerocrossing-based speech processing strategy could more efficiently convey
      Mandarin tonal information than the traditional continuous-interleaved-sampling
      (CIS) method, even when the Mandarin voices were contaminated by the speech
      spectrum shaped noise at low signal-to-noise-ratio levels. It is believed that
      the zerocrossing technique would facilitate the development of novel CI speech
      processor to enhance the pitch perception of cochlear implantees speaking tonal
      language, such as Mandarin.

PMID- 19162662
TI  - Simulation and analysis of needle electromyogram in Emery-Dreifuss muscular
      dystrophy by using line source model.
AB  - Electromyography (EMG) is a valuable clinical test in detection of muscle and
      nerve pathology and distinguishing between myogenic and neurogenic conditions
      from normal condition. By using EMG, one assesses the pathophysiology on the
      basis of the waveform characteristics of the recorded signal. This requires
      detailed knowledge of the relationship between the waveform generators and the
      waveform measurements. In this study, we manipulated parameters of improved line
      source model for normal EMG generation to simulate Emery-Dreifuss Muscular
      Dystrophy (EDMD) disease. Common features of simulated signals in normal and EDMD
      conditions were extracted and quantitative analyses were performed. Finally, the
      simulation results and clinical results were compared and discussed. The results
      indicate the ability and validity of line source model in simulation EDMD disease
      and also confirm that EMG recordings in EDMD generally fulfill the criteria for
      myopathy.

PMID- 19162664
TI  - Respiratory airflow estimation by time varying autoregressive modeling.
AB  - This study proposes an approach to estimate airflow from respiratory sounds using
      time varying autoregressive modeling. Exploiting the well-established
      relationship between respiratory sounds and airflow, the sound signals from
      posterior chest and trachea are modeled using TVAR with a Fourier basis set. It
      is hypothesized that TVAR coefficients will give us an estimate of the amount of
      respiratory airflow. The procedure was tested on a group of healthy subjects and
      good correlation coefficients between the estimated and actual airflow were
      obtained.

PMID- 19162665
TI  - Estimation of muscle strength during motion recognition using multichannel
      surface EMG signals.
AB  - The use of kinesiological electromyography is established as an evaluation tool
      for various kinds of applied research, and surface electromyogram (SEMG) has been
      widely used as a control source for human interfaces such as in a myoelectric
      prosthetic hand (we call them 'SEMG interfaces'). It is desirable to be able to
      control the SEMG interfaces with the same feeling as body movement. The existing
      SEMG interface mainly focuses on how to achieve accurate recognition of the
      intended movement. However, detecting muscular strength and reduced number of
      electrodes are also an important factor in controlling them. Therefore, our
      objective in this study is the development of and the estimation method for
      muscular strength that maintains the accuracy of hand motion recognition to
      reflect the result of measured power in a controlled object. Although the
      muscular strength can be evaluated by various methods, in this study a grasp
      force index was applied to evaluate the muscular strength. In order to achieve
      our objective, we directed our attention to measuring all valuable information
      for SEMG. This work proposes an application method of two simple linear models,
      and the selection method of an optimal electrode configuration to use them
      effectively. Our system required four SEMG measurement electrodes in which
      locations differed for every subject depending on the individual's
      characteristics, and those were selected from a 96ch multi electrode using the
      Monte Carlo method. From the experimental results, the performance in six normal
      subjects indicated that the recognition rate of four motions were perfect and the
      grasp force estimated result fit well with the actual measurement result.

PMID- 19162666
TI  - Interpretability of anatomical variability analysis of abdominal organs via
      clusterization of decomposition modes.
AB  - Extensive recent work has taken place on the construction of probabilistic
      atlases of anatomical organs, especially the brain, and their application in
      medical image analysis. These techniques are leading the way into similar studies
      of other organs and more comprehensively of groups of organs. In this paper we
      report results on the analysis of anatomical variability obtained from
      probabilistic atlases of abdominal organs. Two factor analysis techniques, namely
      principal component analysis (PCA) and principal factor analysis (PFA), were used
      to decompose and study shape variability within the abdomen. To assess and ease
      the interpretability of the resulting deformation modes, a clustering technique
      of the deformation vectors is proposed. The analysis of deformation fields
      obtained using these two factor analysis techniques showed strong correlation
      with anatomical landmarks and known mechanical deformations in the abdomen,
      allowing us to conclude that PFA is a complementary decomposition technique that
      offers easy-to-interpret additional information to PCA in a clinical setting. The
      analysis of organ anatomical variability will represent a potentially important
      research tool for abdominal diagnosis and modeling.

PMID- 19162667
TI  - Joint analysis of differential mobility spectrometer and mass spectrometer
      features for tuberculosis biomarkers.
AB  - In this article, we present results of recent efforts to identify biomarkers for
      tuberculosis using a differential mobility spectrometer (DMS). We focus
      specifically on the capability of exploiting a data collection system that
      employs a DMS in parallel with a mass spectrometer. This system permits
      previously developed algorithms for DMS to be used in conjunction with a device
      considered a gold-standard for chemical identification, making it a unique
      discovery tool for the determination of biomarkers.

PMID- 19162668
TI  - Magnetic resonance imaging of migrating neuronal precursors in normal and hypoxic
      ischemic neonatal rat brains by intraventricular MPIO labeling.
AB  - In this study, 10-day-old normal rats (n=6) and hypoxic-ischemic (H-I) neonatal
      rats (n=6) were injected with the micronsized iron oxide particles (MPIOs) into
      the anterior lateral ventricle. 2D and 3D high-spatial resolution MRI were
      performed with a 7T animal scanner 1 day before the MPIOs injection and hour 3,
      day 3, day 7 and day 14 after the MPIOs injection. Intraperitoneal injections of
      5-bromo-2'-deoxyuridine (BrdU) were used to label newly produced cells, and were
      given thrice daily for 2 days before sacrifice. Immunohistochemistry and Prussian
      blue staining indicated that iron particles were inside the nestin+ and BrdU+
      neural progenitor cells (NPCs), glial-fibrillary-acidic-protein-positive (GFAP+)
      astrocytes-like progenitor cells, and neuronal-nuclei-positive (NeuN+) mature
      neurons. Here we demonstrate that, in normal neonatal rat brain, the migrating
      pathway of the endogenous NPCs with MPIO is mainly along the rostral migratory
      stream to the olfactory bulb. In H-I neonatal rat brain, the migration of
      endogenous NPCs with MPIO is mainly towards the ischemic regions. Therefore, in
      vivo magnetic cell labeling of endogenous NPCs with MPIO and subsequently non
      invasive, serial MRI monitoring should open up a new approach to probe into the
      mechanism of cell migration in the developmental brain under physiological and
      pathologic conditions.

PMID- 19162669
TI  - Preliminary in vitro study of ultrasound sonoporation cell labeling with
      superparamagnetic iron oxide particles for MRI cell tracking.
AB  - Vibration caused by ultrasonic waves can change the structure of cell membrane
      and enhance its permeation. In the last decade, a new ultrasound-aided method,
      sonoporation, has been proposed and utilized to transmit target molecules (such
      as drugs and DNA) into cells for therapy. The objective of this study was to
      investigate the method of loading nanometer-sized superparamagnetic iron oxide
      particles into Sarcoma 180 cells by sonoporation without chemical agents. The
      SPIO nanoparticles were prepared in our laboratory by means of classical
      coprecipitation and the formation of Fe3O4 crystal in SPIO nanoparticles was
      confirmed by x-ray diffraction analysis with its other characteristics assessed
      by magnetic hysteresis loops and size distribution. Cell labeling with SPIOs
      using sonoporation was successfully demonstrated in vitro for sarcoma180 cell
      suspensions from ICR mice. The labeling efficiency and viability were evaluated
      by Prussian blue staining. Such sonoporation technique can be employed for rapid
      labeling of various cells for MRI visualization of their spatiotemporal
      activities in vivo upon transplantation.

PMID- 19162670
TI  - Multi-feature contour evolution for automatic live cell segmentation in time
      lapse imagery.
AB  - Cell boundary segmentation in live cell image sequences is the first step towards
      quantitative analysis of cell motion and behavior. The time lapse microscopy
      imaging produces large volumes of image sequence collections which requires fast
      and robust automatic segmentation of cell boundaries to utilize further automated
      tools such as cell tracking to quantify and classify cell behavior. This paper
      presents a methodology that is based on utilizing the temporal context of the
      cell image sequences to accurately delineate the boundaries of non-homogeneous
      cells. A novel flux tensor-based detection of moving cells provides initial
      localization that is further refined by a multi-feature level set-based method
      using an efficient additive operator splitting scheme. The segmentation result is
      processed by a watershed-based algorithm to avoid merging boundaries of
      neighboring cells. By utilizing robust features, the level-set algorithm produces
      accurate segmentation for non-homogeneous cells with concave shapes and varying
      intensities.

PMID- 19162671
TI  - Watershed deconvolution for cell segmentation.
AB  - Cell segmentation and/or localization is the first stage of a (semi)automatic
      tracking system. We addressed the cell localization problem in our previous work
      where we characterized a typical blood stem cell in a microscopic image as an
      approximately circular object with dark interior and bright boundary. We also
      addressed the modelling of adjacent and dividing cells in our previous work as a
      deconvolution method to model individual blood stem cell as well as adjacent and
      dividing blood stem cells where an optimization algorithm was combined with a
      template matching method to segment cell regions and locate the cell centers. Our
      previous cell deconvolution method is capable of modelling different cell types
      with changes in the model parameters. However in cases where either a complex
      parameterized shape is needed to model a specific cell type, or in place of cell
      center localization, an exact cell segmentation is needed, this method will not
      be effective. In this paper we propose a method to achieve cell boundary
      segmentation. Considering cell segmentation as an inverse problem, we assume that
      cell centers are located in advance. Then, the cell segmentation will be solved
      by finding cell regions for optimal representation of cell centers while a
      template matching method is effectively employed to localize cell centres.

PMID- 19162672
TI  - Simultaneous 3D imaging of morphology and nanoparticle distribution in single
      cells with the Cell-CT technology.
AB  - The Cell-CT is an optical projection tomography microscope (OPTM) developed for
      high resolution 3D imaging of single cells based on absorption stains and
      brightfield microscopy. In this study we demonstrate the use of the Cell-CT in
      multi-color mode for simultaneous imaging of cellular 3D morphology and the 3D
      distribution of nanoparticle clusters in the cytoplasm. The ability to image
      cellular processes in relation to cellular compartments with a non-fluorescence
      3D technology opens new perspectives for molecular research.

PMID- 19162673
TI  - Automatic identification of mycobacterium tuberculosis with conventional light
      microscopy.
AB  - This article presents an automatic identification method of mycobacterium
      tuberculosis with conventional microscopy images based on Red and Green color
      channels using global adaptive threshold segmentation. Differing from
      fluorescence microscopy, in the conventional microscopy the bacilli are not
      easily distinguished from the background. The key to the bacilli segmentation
      method employed in this work is the use of Red minus Green (R-G) images from RGB
      color format. In this image, the bacilli appear as white regions on a dark
      background. Some artifacts are present in the (R-G) segmented image. To remove
      them we used morphological, color and size filters. The best sensitivity achieved
      was about 76.65%. The main contribution of this work was the proposal of the
      first automatic identification method of tuberculosis bacilli for conventional
      light microscopy.

PMID- 19162674
TI  - Methodology for the design of a PACS in a small provincial hospital.
AB  - This paper describes the design and implantation issues for a Picture Archiving
      and Communications System (PACS) in a 60-bed provincial hospital. Considerations
      such as the state of the imaging equipment, preventive maintenance, use and
      misuse of the equipment and the difficulties regarding migration to an all
      digital imaging unit are discussed, as well as the criteria for the selection of
      the imaging modalities. Finally a design is proposed with four imaging modalities
      that use open-source database and display workstations. The system is currently
      under evaluation for possible reproduction in as many as 60 small clinics and
      hospitals throughout the country.

PMID- 19162675
TI  - A graph-based approach to the retrieval of dual-modality biomedical images using
      spatial relationships.
AB  - The increasing size of medical image archives and the complexity of medical
      images have led to the development of medical content-based image retrieval
      (CBIR) systems. These systems use the visual content of images for image
      retrieval in addition to conventional textual annotation, and have become a
      useful technique in biomedical data management. Existing CBIR systems are
      typically designed for use with single-modality images, and are restricted when
      multi-modal images, such as co-aligned functional positron emission tomography
      and anatomical computed tomography (PET/CT) images, are considered. Furthermore,
      the inherent spatial relationships among adjacent structures in biomedical images
      are not fully exploited. In this study, we present an innovative retrieval system
      for dual-modality PET/CT images by proposing the use of graph-based methods to
      spatially represent the structural relationships within these images. We exploit
      the co-aligned functional and anatomical information in PET/CT, using attributed
      relational graphs (ARG) to represent both modalities spatially and applying graph
      matching for similarity measurements. Quantitative evaluation demonstrated that
      our dual-modal ARG enabled the CBIR of dual-modality PET/CT. The potential of our
      dual-modal ARG in clinical application was also explored.

PMID- 19162676
TI  - Multimodal medical case retrieval using the Dezert-Smarandache theory.
AB  - Most medical images are now digitized and stored with semantic information,
      leading to medical case databases. They may be used for aid to diagnosis, by
      retrieving similar cases to those in examination. But the information are often
      incomplete, uncertain and sometimes conflicting, so difficult to use. In this
      paper, we present a Case Based Reasoning (CBR) system for medical case retrieval,
      derived from the Dezert-Smarandache theory, which is well suited to handle those
      problems. We introduce a case retrieval specific frame of discernment theta,
      which associates each element of theta with a case in the database; we take
      advantage of the flexibility offered by the DSmT's hybrid models to finely model
      the database. The system is designed so that heterogeneous sources of information
      can be integrated in the system: in particular images, indexed by their digital
      content, and symbolic information. The method is evaluated on two classified
      databases: one for diabetic retinopathy follow-up (DRD) and one for screening
      mammography (DDSM). On these databases, results are promising: the retrieval
      precision at five reaches 81.8% on DRD and 84.8% on DDSM.

PMID- 19162677
TI  - Sparse representation of complex MRI images.
AB  - Sparse representation of images acquired from Magnet Resonance Imaging (MRI) has
      several potential applications. MRI is unique in that the raw images are complex.
      Complex wavelet transforms (CWT) can be used to produce flexible signal
      representations when compared to Discrete Wavelet Transform (DWT). In this work,
      five different schemes using CWT or DWT are tested for sparse representation of
      MRI images which are in the form of complex values, separate real/imaginary, or
      separate magnitude/phase. The experimental results on real in-vivo MRI images
      show that appropriate CWT, e.g., dual-tree CWT (DTCWT), can achieve sparsity
      better than DWT with similar Mean Square Error.

PMID- 19162678
TI  - A comparison of two methods for retrieval of medical images in the compressed
      domain.
AB  - Retrieval of images based on features derived directly from the images provides a
      useful way of accessing medical imagery. While most of these techniques operate
      in the pixel domain, a more efficient approach is to perform retrieval directly
      in the compressed domain of images. In this paper we look at two different
      methods for such compressed-domain retrieval of medical images. Both algorithms
      are based on wavelet image compression such as the one used in the JPEG2000
      standard. We compare the effectiveness of the two techniques based on a database
      of 400 medical infrared images.

PMID- 19162679
TI  - Using relevance feedback to reduce the semantic gap in content-based image
      retrieval of mammographic masses.
AB  - This paper presents the use of relevance feedback (RFb) to reduce the semantic
      gap in content-based image retrieval (CBIR) of mammographic masses. Tests were
      conducted where the radiologists' classification of the lesions based on the BI
      RADS categories were used with techniques of query-point movement to incorporate
      RFb. The measures of similarity of images used for CBIR were based upon Zernike
      moments. The performance of CBIR was measured in terms of precision and recall of
      retrieval. The results indicate improvement due to RFb of up to 41.6% in
      precision. In our experiments, the gain in the performance of CBIR with RFb was
      associated with the BI-RADS category of the query mammographic image, with large
      improvement in cases of lesions belonging to categories 4 and 5. The proposed
      method could find applications in computer-aided diagnosis (CAD) of breast
      cancer.

PMID- 19162680
TI  - Coronary angiogram video compression adapted to medical imaging applications.
AB  - H.264/AVC coder has proven to use the most advanced video compression, but, at
      the cost of high computational complexity. On the other hand, analysis of
      coronary x-ray images reveals large areas containing no diagnostically important
      information. In this paper, we propose to exploit the energy characteristics in
      slice equal size regions to determine the active zones in coronary x-ray
      sequences to be encoded as normal using the H.264 coding system. The other
      regions, are compressed using conventional low complex approaches. Experimental
      results have shown that this procedure reduces the coder computing time of about
      20% while attaining the same compression performance. A clinical subjective
      assessment by three expert physicians in interventional cardiology leads to a
      compression ratio of about 30:1 which insures both a diagnosis adequacy and a
      sufficient compression in regards to storage and transmission requirements.

PMID- 19162681
TI  - Medical image integrity control seeking into the detail of the tampering.
AB  - In this paper, we propose a system which aims at verifying integrity of medical
      images. It not only detects and localizes alterations, but also seeks into the
      details of the image modification to understand what occurred. For that latter
      purpose, we developed an image signature which allows our system to approximate
      modifications by a simple model, a door function of similar dimensions. This
      signature is partly based on a linear combination of the DCT coefficients of
      pixel blocks. Protection data is attached to the image by watermarking. Whence,
      image integrity verification is conducted by comparing this embedded data to the
      recomputed one from the observed image. Experimental results with malicious image
      modification illustrate the overall performances of our system.

PMID- 19162682
TI  - Analysis of digital image quality indexes for CIRS SP01 and CDMAM 3.4
      mammographic phantoms.
AB  - Mammographic phantom images are usually used to study the quality of images
      obtained by determined mammographic equipment. The digital image treatment
      techniques allow carrying out an automatic analysis of the phantom image.
      Nowadays, the digital radiographic equipments are replacing the traditional film
      screen equipments and it is necessary to update the parameters to guarantee the
      quality of the process. In this work we apply some techniques of digital image
      processing to compute a specific image quality indexes for mammographic phantoms,
      namely CIRS SP01 and CDMAM 3.4. to study the evolution of this parameter with
      different varying conditions of the mammographic equipment. The indexes are
      calculated from a scoring system based on a designed algorithm which analyses the
      phantom image by means of an automatic detection of the test objects in each
      phantom.

PMID- 19162683
TI  - Further development in anatomically constrained MR image reconstruction:
      application to multimodal imaging of mouse stroke.
AB  - MR imaging can leverage a wide variety of intrinsic contrast mechanisms to
      provide detailed information regarding the anatomy, function, physiology, and
      metabolism of biological tissues. However, because of low sensitivity, many
      experiments that reveal higher-order structure and function have been limited due
      to inherent trade-offs between data acquisition time, signal-to-noise ratio, and
      resolution. This paper describes the further development of a statistical
      framework for MR image reconstruction which helps to mitigate these effects.
      Specifically, we advocate the collection of high-resolution multi-modal MR
      imaging data, and utilize the correlation between features in these different
      images to reduce noise while maintaining resolution. The proposed approach is
      illustrated with joint reconstruction of relaxometry and spectroscopic imaging
      data in a mouse model of stroke.

PMID- 19162684
TI  - Modeling log-compressed ultrasound images for radio frequency signal recovery.
AB  - This paper presents an algorithm for recovering the radio frequency (RF) signal
      provided by the ultrasound probe from the log-compressed ultrasound images
      displayed in ultrasound equipment. Commercial ecographs perform nonlinear image
      compression to reduce the dynamic range of the Ultrasound (US) signal in order to
      improve image visualization. Moreover, the clinician may adjust other parameters,
      such as brightness, gain and contrast, to improve image quality of a given
      anatomical detail. These operations significantly change the statistical
      distribution of the original RF raw signal, which is assumed, based on physical
      considerations on the signal formation process, to be Rayleigh distributed.
      Therefore, the image pixels are no longer Rayleigh distributed and the RF signal
      is not usually available in the common ultrasound equipment. For statistical data
      processing purposes, more important than having "good looking" images, it is
      important to have realistic models to describe the data. In this paper, a
      nonlinear compression parametric function is used to model the pre-processed
      image in order to recover the original RF image as well the contrast and
      brightness parameters. Tests using synthetic and real data and statistical
      measures such as the Kolmogorov-Smirnov and Kullback-Leibler divergences are used
      to assess the results. It is shown that the proposed estimation model clearly
      represents better the observed data than by taking the general assumption of the
      data being modeled by a Rayleigh distribution.

PMID- 19162685
TI  - Model-based super-resolution for MRI.
AB  - Conventional 1.5 T magnetic resonance imaging (MRI) systems suffer from poor out
      of-plane resolution (slice dimension), usually with in-plane resolution being
      several times higher than the former. Post-acquisition, super-resolution (SR)
      filtering is a viable alternative and a less expensive, off-line image processing
      approach that is employed to improve tissue resolution and contrast on acquired
      three-dimensional (3D) MR images. We introduce an SR framework that models a true
      acquired volume information by taking into account slice thickness and spacing
      between slices. Previous SR schemes have not considered this type of acquisition
      information or they have required specialized MR acquisition techniques.
      Evaluations based on synthetic data and clinical knee MRI data show superior
      performance of this method over an existing averaging method.

PMID- 19162686
TI  - Convex ultrasound image reconstruction with log-Euclidean priors.
AB  - Image reconstruction from noisy and incomplete observations is usually an ill
      posed problem. A Bayesian framework may be adopted do deal with this such inverse
      task by well posing the reconstruction problem. In this approach, the ill
      poseness nature of the reconstruction is removed by minimizing a two-term energy
      function. The first term pushes the solution toward the data and the second
      regularizes the solution. A Bayesian algorithm for ultrasound image
      reconstruction and de-noising is proposed where an edge preserving prior is used
      to reduce the smoothing effect at the transitions. The prior distribution is
      based on log-Euclidean potential functions that are particular suitable in
      reconstruction problems under the constraint of positivity, that is, when the
      unknowns to be estimated should be positive, which is the case, where the noisy
      observations are modeled by a Rayleigh distribution. In this paper, the
      reconstruction procedure is formulated as the optimization of a convex function
      and a Newton method is adopted to obtain the minimizer. This strategy guarantees
      a convergence to the global minimum in a small number of iterations. Experimental
      results, using synthetic and real medical images are shown. The proposed method
      produces images where speckle noise is effectively suppressed and important
      clinical details (organ and tissue transitions) are preserved.

PMID- 19162687
TI  - A comparison study of regularization techniques on the theoretical design of
      phased array RF coils in MRI.
AB  - In MRI engineering, regularization techniques can be effectively used to solve
      ill-posed problems in electromagnetics, such as the inverse design of phased
      array RF coils. In this work, a comparison on various regularization methods
      which are employed to numerically reconstruct a divergence-free cylindrical
      surface of current distribution is investigated. It is found that a coil current
      pattern is very sensitive to the modes of the basis function describing the
      current densities on the coil surface; and iterative regularization techniques
      generally produce better B(1) field profiles compared with direct approaches.

PMID- 19162688
TI  - Total variation with automatic hyper-parameter estimation.
AB  - Medical diagnosis is often hampered by the quality of the images. This happens in
      a wide range of image modalities. Image noise reduction is a crucial step,
      however difficult to be accomplished. Bayesian algorithms have been commonly used
      with success, namely with additive white Gaussian noise (AWGN) model. In fact,
      the noise corrupting some of the most used medical imaging modalities is not
      additive neither Gaussian but multiplicative described by Poisson or Rayleigh
      distributions. This paper proposes a unified framework with automatic hyper
      parameters estimation. The proposed framework deals with AWGN but also with both
      Poisson and Rayleigh distributions. The algorithm proposed herein, is based on a
      maximum a posteriori (MAP) criterion with the edge preserving prior based on the
      total variation (TV), which avoids the distortion of relevant anatomical details.
      The denoising technique is performed via single parametric iterative scheme
      parameterized for each noise model considered. Tests with real data from several
      medical imaging modalities testify the performance of the algorithm.

PMID- 19162689
TI  - Simulation of skin reflectance images using 3D tissue modeling and multispectral
      Monte Carlo light propagation.
AB  - In this work we propose a method to simulate the expected, i.e. seen by a camera,
      multispectral reflectance images of a large skin surface area by combining Monte
      Carlo light propagation model and realistic tissue modeling based on three
      dimensional data acquisition of human body areas. In particular, we aim to
      simulate more accurately light transport in biological tissue by taking into
      account the geometrical topography of the skin surface, the structure and optical
      properties of the skin layers, and the subcutaneous veins in presence. We
      describe our computation method in detail and present simulated reflectance
      images results.

PMID- 19162690
TI  - Rigid diffusion phantom: acquisition and simulation.
AB  - Diffusion tensor imaging has already been a popular imaging modality for clinical
      researches. However, to setup an imaging protocol is not straightforward. This
      problem is critical issue for multi-center studies. We developed anisotropy
      phantoms and examined the feasibility of using water-filled arrays of channeled
      silicon plates. Various channel sizes were tested to optimize the diffusion and
      anisotropy properties. We succeeded in producing a phantom with high anisotropy
      (FA=0.8). However, a reason of high axial diffusivity needs further
      investigations.

PMID- 19162691
TI  - 3D simulation of diffraction in ultrasonic computed tomography.
AB  - The contribution presents further results in developing the exact means for
      simulating the realistic situation in the USCT (ultrasonic computed tomography)
      imaging system, aiming both at evaluating the approximations used in the existing
      USCT image reconstruction methods as to their precision and also (in a longer
      perspective) at iterative improvement of the obtained images via continuum
      mechanics based feedback. The mathematical models, generalised in comparison with
      [1], emerging from the transparent physical background, are presented for
      inhomogeneous media incorporating both the object tissue and the surrounding
      fluid. The equations are already general enough to employ complex nonlinear
      phenomena in three-dimensional space; and linearised 3D simulations (giving rise
      to wave equation, WE) have been performed enabling first conclusions on the
      feasibility of this approach with respect to the available computing resources.
      Some of the results of the numerical solution of the WE in 3D by means of the
      finite-element method show in local detail the diffraction phenomena on acoustic
      impedance inhomogeneities. The spatial extent of the simulations is basically
      limited only by the available computing resources. The hardware requirements and
      related practical limitations are mentioned together with a few examples of
      presently available results. Together with conclusions, further perspectives of
      this branch of the USCT research are suggested.

PMID- 19162692
TI  - Backprojection-based imaging geometric parameter estimation.
AB  - In SPECT (single photon emission computed tomography) and X-ray CT, point sources
      are commonly used to acquire data for imaging parameter estimation. The
      parameters are estimated by fitting the point source projection data to a
      mathematical model of the imaging system. This paper introduces two
      backprojection-based parameter estimation methods. In the first method a point
      source is attached to the object; the second method is data-based without using a
      point source at all.

PMID- 19162693
TI  - An Adaptive Multigrid method for modeling photon transport through biological
      tissues in bioluminescence tomography.
AB  - In this paper, we develop an Adaptive Multigrid method (AMGM) to model photon
      transport through biological tissues in bioluminescence tomography. In our
      method, the smoothing operation on fine levels and residual correction on coarse
      levels in V-Cycle offer fast convergence rate for this forward problem. Using a
      heterogeneous phantom, the methodology is validated by Monte Carlo simulations,
      and the computation speed is much higher than conventional smoothing iteration
      methods on a single grid. In actual biomedical imaging applications, especially
      when there are many sources in small animal body, AMGM is potential to accurately
      simulate the forward problem at very low computation cost.

PMID- 19162694
TI  - Three dimensional electrical impedance tomography in thorax complete model.
AB  - The forward problem and the inverse problem are both researched. The opposite
      drive pattern is adopted with single drive current pattern. The potential
      distributions of inhaling and exhaling models are gotten in the forward problem,
      which are obtained by finite element method. The inverse problem is realized by
      Homotopy-Newton-Raphson algorithm, which needs times of revising the impedance
      after comparing the measuring potentials and the computing ones on the
      electrodes. The solution of the inverse problem is benefit for monitoring the
      activities in the thorax, such as inhaling and exhaling. Three dimensional
      electrical impedance tomography in the thorax complete model is provided in this
      paper, which is consisted with lung, muscle, heart and spinal column.

PMID- 19162695
TI  - Calibration of X-ray radiographs and its feasible application for 2D/3D
      reconstruction of the proximal femur.
AB  - In the past ten years, a variety of computer-assisted surgical technologies have
      been introduced for total hip replacement (THR). Despite the different
      approaches, orthopedic surgeons routinely still acquire 2D X-ray radiographs for
      preoperative diagnostic and templating purposes. Such images provide detailed
      information in high resolution about the underlying anatomy. But lack of
      knowledge about the magnification factor of the bony structures complicates the
      correct interpretation of the real anatomy and therefore could lead to
      mismatching implants intraoperatively based on the preoperative performed
      planning. Therefore we developed a calibration device, which can be mounted
      within the usual clinical environment and allows to improve the accuracy of
      conventional radiographs by applying a specific calibration algorithm.
      Furthermore, we investigated the feasibility of reconstructing the surface of the
      proximal femur on the basis of two calibrated X-ray radiographs. The accuracy of
      this approach has been thoroughly validated using 14 dry cadaver femur bones
      (pathological as well as non-pathological cases), one plastic femur bone and one
      wet cadaver pelvis.

PMID- 19162696
TI  - A preliminary study on discrimination of osteoporotic fractured group from
      nonfractured group using support vector machine.
AB  - Osteoporosis is characterized by an abnormal loss of bone mineral content, which
      leads to a tendency to non-traumatic bone fractures or to structural deformations
      of bone. Thus, bone density has been considered as a most reliable parameter to
      assess osteoporotic fracture risk. In past decades, by the way, bone texture
      measures have been studied to estimate other aspect of bone quality. Some studies
      have been performed on CT or MR images to assess bone quality using trabecular
      structure analysis. Other studies have been performed on plain x-ray images or
      ultrasound images to assess trabecular structure. However, most of the studies
      are focused on individual parameters to distinguish between osteoporotic
      fractured group and nonfractured group. In this preliminary study, we combine
      various texture parameters with bone density parameters using a support vector
      machine and point out the most promising combination of parameters to distinguish
      between osteoporotic fractured group and nonfractured group.

PMID- 19162697
TI  - Automatic extraction of local axis of bone symmetry in CT images.
AB  - We present an algorithm that extracts local axis of symmetry in CT images
      automatically. The proposed method combines registration and extraction of bone
      contours to generate the desired symmetry axis. The method consists of several
      stages: first extracting the bone contours of the images by using an active
      contour method, then finding grossly an axis that allows the division of the
      image into two parts, loosely called 'half' images, but with the understanding
      that they are not exactly the two halves of the image but rather the two halves
      of the depicted object. After that, finding a mapping that aligns the first half
      of the image with the second half and finally, finding the local axis of symmetry
      from corresponding contours.

PMID- 19162698
TI  - A density distance augmented Chan-Vese active contour for CT bone segmentation.
AB  - Bone segmentation from Computed Tomography (CT) images is a critical component in
      computer-assisted orthopedic surgery but is a challenging task. Among many active
      contour (AC) models employed to solve the problem, the Chan-Vese AC [1] yields
      superior performances as evaluated in [2]. However, the CV AC fails to correctly
      extract the objects that are of high inhomogeneity because its nature is the
      minimization of the differences within the objects. In this paper, we propose to
      incorporate a Bhattacharrya term to the CV functional which helps to maximize the
      distance between the density functions of the objects and the background. The
      proposed model is tested with various synthetic and real CT images. Preliminary
      experimental results show that it can overcome the limitation of the CV AC.

PMID- 19162699
TI  - Automatic segmentation of cortical and trabecular components of bone specimens
      acquired by pQCT.
AB  - Peripheral Quantitative Computerized Tomography (pQCT) allows the acquisition of
      bone specimens with a spatial resolution adequate to visualize the 3D structure
      of the bone cortex and the trabecular network. At present, pQCT scanners are
      equipped with image processing software that limits the bone analysis in two
      dimensions and requires strong user interaction. In this work, a method is
      proposed to automatically segment, in 3D, cortical and trabecular components of
      bone specimens acquired by pQCT, in order to facilitate and enhance the
      quantitative evaluation of densitometric properties of the bone.

PMID- 19162700
TI  - Automatic extraction of mandibular bone geometry for anatomy-based synthetization
      of radiographs.
AB  - We present an automatic method for segmenting Cone-Beam Computerized Tomography
      (CBCT) volumes and synthetizing orthopantomographic, anatomically aligned views
      of the mandibular bone. The model-based segmentation method was developed having
      the characteristics of dental CBCT, severe metal artefacts, relatively high noise
      and high variability of the mandibular bone shape, in mind. First, we applied the
      segmentation method to delineate the bone. Second, we aligned a model resembling
      the geometry of orthopantomographic imaging according to the segmented surface.
      Third, we estimated the tooth orientations based on the local shape of the
      segmented surface. These results were used in determining the geometry of the
      synthetized radiograph. Segmentation was done with excellent results: with 14
      samples we reached 0.57+/-0.16 mm mean distance from hand drawn reference. The
      estimation of tooth orientations was accurate with error of 0.65+/-8.0 degrees.
      An example of these results used in synthetizing panoramic radiographs is
      presented.

PMID- 19162701
TI  - Smart garments for emergency operators: results of laboratory and field tests.
AB  - The first generation of ProeTEX prototypes has been completed at the end of
      August 2007. In the following period two main activities have involved the
      project partners. On one hand new technologies (in terms of sensors and devices)
      to be integrated in the next releases of prototypes have been developed; on the
      other hand intensive test sessions on the first prototype (both in laboratory
      conditions and simulating real operative scenarios) have been carried out. This
      paper is mainly focused on this second facet. Great efforts have been dedicated
      to the trials for different reasons: firstly to investigate the appropriateness
      and efficiency of the system in normal and harsh conditions; secondly to obtain
      useful indications regarding usability and efficacy by the end-users involved in
      the project. The results of the trials have been used to define the
      specifications of the second generation of prototypes, that will be released
      within the end of 2008.

PMID- 19162702
TI  - Wireless fall sensor with GPS location for monitoring the elderly.
AB  - Falls of the elderly has become a major public health problem in our modern
      society. It is both the first cause of accidental death, but also the beginning
      of the loss of autonomy from these people. In this context, the paper describes a
      solution based on an energy-efficient embedded device capable of detecting the
      fall, to send a warning to a control and monitoring processing station and to
      locate the person in a close external environment. Fall detection, location,
      processing and signal analysis, and data transmission are provided by an
      accelerometer, a GPS receiver, a microcontroller and a Zigbee technology
      transceiver.

PMID- 19162703
TI  - Fast prototype of a wireless cardiac rhythm interpretive instrument.
AB  - Extended patient monitoring has become increasingly important for detection of
      cardiac conditions, such as irregularities in the rhythms of the heart, while
      patient is practicing normal daily activity. This paper presents a design of a
      single lead wireless cardiac rhythm interpretive instrument that capable of
      capture the electrocardiogram (ECG) in digital format and transmitted to a remote
      base-station (i.e. PC) for storage and further interpretation. The design has
      achieved high quality of ECG and free of interference in the presence of motion.

PMID- 19162704
TI  - An integrated platform to assess driver's physiological and functional states.
AB  - Physiological signals like Heart Rate, Respiration and Skin Resistance are
      relevant indicators to evaluate driver's mental state. Therefore, most methods
      based on physiological signals measurements have been improved on driving
      simulators or in experimental laboratories under carefully controlled conditions
      and rigorous protocols. To study driver's behavior in actual conditions, we have
      developed an in-vehicle system which could record contextual driving information,
      drivers' actions and physiological signals related to them. Recordings from the
      driver and the vehicle may give valuable information for a close estimation of
      driver's functional state, its evolution across time and thus a better
      understanding of driver's behavior. This system provides specific patterns
      related to the driver's functional state, according to the driving context. This
      paper is aimed to present the design and implementation of this system, well
      adapted to ergonomics.

PMID- 19162705
TI  - A system for assessing motion artifacts in the signal of a micro-optic in-ear
      vital signs sensor.
AB  - Cardiovascular diseases are among the most common causes of death in developed
      industrial nations. It is of great interest of both physician and patient to
      determine the cardiovascular risk factors early in order to take preventive
      measures. To assist these investigations we develop a wearable in-ear measuring
      system (IN-MONIT) for 24/7 monitoring of heart rate and oxygen saturation (SpO2).
      The central component is a micro-optic remission/reflection sensor (MORES)
      located inside the auditory canal. From the measured photoplethysmographic curves
      the aforementioned vital signs can be derived. In the following we present a
      recording system for assessing motion artifact influence in the in-ear sensor
      data. Two accelerometer sensors record posture and motion while at the same time
      SpO2, heart rate and PPG are measured using both a commercial sensor and the in
      ear sensor. The data is transmitted wirelessly to a control PC for storage and
      further investigation. Using this system we assessed the influence of motion
      artifacts produced by daily life activities on infrared and red in-ear PPG data
      and on readings of the reference sensor.

PMID- 19162706
TI  - Assessment of sleep/wake patterns using a non-contact biomotion sensor.
AB  - We evaluate a contact-less continuous measuring system measuring respiration and
      activity patterns system for identifying sleep/wake patterns in adult humans. The
      system is based on the use of a novel non-contact biomotion sensor, and an
      automated signal analysis and classification system. The sleep/wake detection
      algorithm combines information from respiratory frequency, magnitude, and
      movement to assign 30 s epochs to either wake or sleep. Comparison to a standard
      polysomnogram system utilizing manual sleep stage classification indicates
      excellent results. It has been validated on overnight studies from 12 subjects.
      Wake state was correctly identified 69% and sleep with 88%. Due to its ease-of
      use and good performance, the device is an excellent tool for long term
      monitoring of sleep patterns in the home environment in an ultraconvenient
      fashion.

PMID- 19162707
TI  - Sensitivity of a single coil electromagnetic sensor for non-contact monitoring of
      breathing.
AB  - We design and analyse a flexible non-contact electromagnetic sensor for
      monitoring breathing. This paper presents the sensor design and the theoretical
      model for the expected sensitivity from which we optimize design components. The
      primary application of this device is in non-invasive sleep monitoring and it has
      the potential to be useful for detection of both adult and infant apnea. The
      conductivity changes of the lungs during breathing are monitored by inducing eddy
      currents within them. The sensor consists of a small coil that acts as both a
      transmitter and a receiver. The theoretical sensitivity of the sensor to
      breathing changes is calculated and corresponds within the assumptions of the
      model to the measured results.

PMID- 19162708
TI  - Automatic home care system for monitoring HR/RR during sleep.
AB  - This paper described an automatic home care system for monitoring HR/RR during
      sleep. Pressure signal is measured with a completely unconstrained pressure
      sensor beneath a pillow; then the signal is digitalized and the data are
      transmitted to a remote server using TCP/IP via a netbox. The data are processed
      and analyzed with a wavelet-based algorithm to obtain the heart rate and
      respiration rhythm during sleep. Through analyzing 180 days' data obtained from a
      female subject, it was found that this system can be used for daily monitoring
      heart rate and respiration rhythm during sleep and evaluating the quality of
      sleep at home.

PMID- 19162709
TI  - Development of the device to detect human's bio-signals by easy sensing.
AB  - A disaster like a big earthquake usually destroys many buildings and generates
      many sufferers. In this situation, sometimes a rescue person encounters a second
      disaster. This is the big problem to rescue sufferers. In order to avoid a second
      disaster, many kinds of rescue robots are being developed. These robots can find
      sufferers and rescue them. However, they cannot measure the sufferer's condition
      at the disaster area. If the sufferer's condition becomes clear before rescue, it
      makes rescue action more efficient and will be useful for the triage. So, we are
      investigating the measure system which can be installed on a rescue robot and
      obtain vital signs of sufferers easily at the disaster area. In this paper, we
      will describe developed methods that can measure ECG (Electrocardiogram) and SpO2
      (the arterial blood oxygen saturation degree) by easy way. We think that these
      methods will be powerful and useful to rescue sufferers.

PMID- 19162710
TI  - Film-type transducer materials PVDF and EMFi in the measurement of heart and
      respiration rates.
AB  - Film-type transducer materials polyvinylidenefluoride (PVDF) and
      ElectroMechanical Film (EMFi) were used in the measurement of heart and
      respiration rates on the chest wall at rest. The aim here was to evaluate if the
      both materials are capable to measure the heart and respiration rates correctly
      and also to found out if there are differences between the results of PVDF and
      EMFi. The movements provided by the pulsation of heart and respiration were
      converted into an electrical signal by the sensors. The signals were amplified
      and transmitted to a computer. The data was analyzed with Matlab software. The
      signals were filtered to reveal the heart pulsation and respiration components.
      Power spectral density (PSD) spectrum was computed to determine the heart and
      respiration rates. ECG was used as a reference signal for the heart rate and a
      thermistor for the respiration rate. Both transducer materials provided good
      results and no differences between PVDF and EMFi were found. The heart rates
      measured with PVDF and EMFi sensors corresponded to the values calculated from
      the ECG signal. Also the respiration rates correlated with the values determined
      with the thermistor. To conclude, both materials provided reliable results in the
      measurements of heart and respiration rates.

PMID- 19162711
TI  - Development of bio-signal measurement system for sports healthcare.
AB  - The purpose of this study is to determine an individual physiological signal and
      based on the information; develop equipment that will encourage the efficiency of
      exercise. To evaluate the practical use of equipment an experiment is carried
      out. The signal of twenty adult male is determined under condition of Exercise
      Stress Test. Measured physiological signals are ECG from ears, chest (Lead I),
      PPG from earlap, activity from ear and arm, and the body skin temperature of arm.
      For ECG data, there are two signals: one is ear-arm signal, and the other is
      chest (Lead I) signal. When compare those two, ear-arm detection rate shows
      92.08% detection, and 93.13% at chest. The error rate occurred average 0.035(+/
      0.014) seconds and 0.026(+/-0.017) seconds. For PPG, we can reduce the influence
      of motion artifact by Autocorrelation method, and as a result, peak detection
      rate increased from 94.3% to 98.4%, decreased the error rate with 0.058+/-0.076
      to 0.023+/-0.031, Also, we certified that if the speed and elevation of the
      treadmill increase, physical activity increase, and the body temperature gets
      decreased. Upon this consequence, we developed a physiological data acquisition
      system that is convenient to user while they are exercising.

PMID- 19162712
TI  - Ratpack: wearable sensor networks for animal observation.
AB  - The goal of our project is to describe the behavior of rats. For this purpose we
      are using wireless sensor networks, monitoring various quantities that yield
      important information to complement current knowledge on the behavioral
      repertoire of rats. So far, on the sensing and processing side we have developed
      innovative, minimalist approaches pointing in two directions: vocalization
      analysis and movement tracking. On the data collection and routing side we have
      adapted to the known burrowing habits of rats by developing new methods for
      synchronization and data aggregation under the paradigm of sporadic connectivity
      in a sparse, dynamic network.

PMID- 19162713
TI  - A handle electrode system for measuring heart rate while riding a bicycle.
AB  - In this paper, a handle-electrode system is proposed for obtaining the heart rate
      of a user while riding a bicycle. The system was designed to measure the user's
      heart rate by only gripping the handle of a bicycle. Three electrodes made from
      conductive cloth were adhered to the handle. A method detecting heart-rate from
      the obtained electrocardiogram was also proposed. To assess the applicability of
      the proposed system, a simple experiment was performed. The experiment was
      performed in four conditions of road surfaces; lawn, asphalt, a tiled, and an
      uneven road. Experimental result suggests that the proposed system can be useful
      for obtaining R waves while riding a bicycle.

PMID- 19162714
TI  - Exquisite textiles sensors and wireless sensor network device for home health
      care.
AB  - In this study, we propose a wearing system with four sensors, ECG
      (electrocardiogram), three-axis accelerometer, temperature, and tight-switch,
      applied for remote monitoring system in home-care. The sensors ECG, measured with
      wearable electrodes made of the steel textile to generate the real-time heart
      rate estimator, tight-switch, made of the steel textile to check whether wearing
      person dresses properly, accelerometer, and temperature parameters are received
      via the ZigBee receiver within an exquisite belt. Since the movable textile
      electrodes will cause of unfixed contacts when the wearing person is in motion,
      making the heart-rate estimation much a sophisticated work, the tight-switch
      sensor and FIR (Filter Impulse Response) filter technology are applied here to
      get the more satisfiable heart-rate. The other two bio-sensors can detect the
      whether fall-down or not and normal body-temperature of this wearing person.
      Moreover, the ZigBee device with small size, low-power consumption, and high
      reliability characteristics is designed to transmit the detected bio-information
      from these four sensors. Therefore, the vital system embedded with the capability
      of real-time heart-rate estimation and transmission makes it highly suitable for
      applications of remote healthcare and wellness.

PMID- 19162715
TI  - Computed myography (CMG): three dimensional reconstruction of motor functions
      from surface EMG data.
AB  - We describe a methodology to qualitatively and quantitatively determine the
      activation level of individual muscles by voltage measurements from an array of
      voltage sensors on the skin surface. A physical finite element model for
      electrostatics simulation is constructed from morphometric data and numerical
      inversion techniques are used to determine muscle activation patterns.
      Preliminary results from experiments with simulated and human data are presented
      for activation reconstructions of three muscles in the upper arm (biceps brachii,
      bracialis, and triceps). This approach potentially offers a new clinical tool to
      sensitively assess muscle function in patients suffering from neurological
      disorders (e.g., spinal cord injury) and could more accurately guide advances in
      the evaluation of specific rehabilitation training regimens.

PMID- 19162716
TI  - A mesh-free mechanical model of the upper gastrointestinal system.
AB  - Realistic behavior in Computer Simulation of biological system (e.g. humans
      organs) is essential to 3D modeling in medicine. In order to improve realistic
      responses of 3D organ model it is essential to use mechanical models that can
      deal with multiple objects internal and external interactions in a reasonable
      time frame. We will apply the Smooth Particles Hydrodynamics (SPH) to model the
      esophagus and the stomach, thus constructing a physical background for
      interaction. We used a multilayer model of particles related to a single triangle
      mesh. Each particle layers represent distinct biological tissues of the esophagus
      and the stomach.

PMID- 19162717
TI  - An electrical model of the cell-electrode interface for high-density
      microelectrode arrays.
AB  - A point-contact model is presented, and an area-contact model has been
      analytically derived in order to model the electrical characteristic of the cell
      electrode interface of high-density neuron cultures. The area-contact model is
      presented as a model more suitable for subcellular multi-electrode resolution,
      which is a requisite for modeling and simulating the electrical behavior of novel
      high-density microelectrode arrays. Furthermore, when the electrode is aligned
      and centered with the cell, an optimum electrode diameter for recording the
      electrical activity of neural cells can be analytically derived, which is between
      7-8 microm with a typical load capacitance of 10 pF.

PMID- 19162718
TI  - Charge distributions of active biological pores.
AB  - Charge distributions associated with active biological pores are calculated. The
      charge distributions include rings of reverse-sign, current-turning charges which
      surround the entrance and exit ends of the pore and cause current to turn into
      the pore at its entrance end (e.g., the intracellular side of a potassium pore)
      and to turn outward from the pore at its exit end (e.g., the extracellular side
      of a potassium pore). The magnitude and spatial extent of the rings depend
      directly on the magnitude of the current passing through the pore. In the absence
      of current, the rings disappear and when, for example, the pore's resistance
      becomes the dominant resistance in the system, the magnitude and spatial extent
      of the rings saturate. The reverse-sign, current-turning charges affect the local
      environment of proteins, such as ligand-binding proteins, known to reside
      adjacent to biological pores. The charges are thus expected to play a role in
      pore function such as by modulating the binding of charged species to the binding
      proteins.

PMID- 19162719
TI  - Muscle reflection human computer model in wheelchairs traveling in motor
      vehicles.
AB  - In this study, a human motion computer model in a wheelchair was developed to
      evaluate the effectiveness of a seatbelt for disabled people traveling in a motor
      vehicle. The human model was composed of two rigid links and three masses. This
      model was characterized with muscle reflection defined by Hill's equation. A
      sudden stop experiment by using a carriage on which a wheelchair was fixed with a
      subject was performed to obtain the human muscle parameters and to evaluate the
      model. Volunteer subjects including disabled people participated in the
      experiment. The motion and muscle activity of a subject wearing a seatbelt were
      simulated by this model. The muscle reflection of disabled people was stronger
      than that of normal people in the case of not using a seatbelt, but in the case
      of using a seatbelt the muscle reflection of disabled people was similarly weak
      with normal people. The result of computer simulation showed that a seatbelt is
      more important for disabled people than for normal people.

PMID- 19162720
TI  - A platform for in silico modeling of physiological systems II. CellML
      compatibility and other extended capabilities.
AB  - The number of biological models published in peer reviewed journals and
      complexity of each of those models are rapidly increasing, making it difficult to
      reproduce simulation results of the published models and to reuse the models by
      third persons. This paper is a continuation of our previous report on a software
      platform development as a solution to such difficulties. We describe progresses
      of our development. Those include improvement in functional capabilities to
      import and simulate published models in the CellML model repository, to browse
      and edit CellML models and then to export them as new models either with the
      CellML format or with a XML format defined for our platform (ISML), and to newly
      construct large scale models by connecting CellML/ISML models. Several advantages
      to use ISML in parallel with CellML are; 1) ISML can deal with geometry
      (morphology) of a model, enabling the user to perform geometry dependent modeling
      and simulations. 2) ISML can deal with time series data, both simulated and
      experimentally acquired data, for visualization of dynamics.

PMID- 19162721
TI  - Large scale cardiac modeling on the Blue Gene supercomputer.
AB  - Multi-scale, multi-physical heart models have not yet been able to include a high
      degree of accuracy and resolution with respect to model detail and spatial
      resolution due to computational limitations of current systems. We propose a
      framework to compute large scale cardiac models. Decomposition of anatomical data
      in segments to be distributed on a parallel computer is carried out by optimal
      recursive bisection (ORB). The algorithm takes into account a computational load
      parameter which has to be adjusted according to the cell models used. The
      diffusion term is realized by the monodomain equations. The anatomical data-set
      was given by both ventricles of the Visible Female data-set in a 0.2 mm
      resolution. Heterogeneous anisotropy was included in the computation. Model
      weights as input for the decomposition and load balancing were set to (a) 1 for
      tissue and 0 for non-tissue elements; (b) 10 for tissue and 1 for non-tissue
      elements. Scaling results for 512, 1024, 2048, 4096 and 8192 computational nodes
      were obtained for 10 ms simulation time. The simulations were carried out on an
      IBM Blue Gene/L parallel computer. A 1 s simulation was then carried out on 2048
      nodes for the optimal model load. Load balances did not differ significantly
      across computational nodes even if the number of data elements distributed to
      each node differed greatly. Since the ORB algorithm did not take into account
      computational load due to communication cycles, the speedup is close to optimal
      for the computation time but not optimal overall due to the communication
      overhead. However, the simulation times were reduced form 87 minutes on 512 to 11
      minutes on 8192 nodes. This work demonstrates that it is possible to run
      simulations of the presented detailed cardiac model within hours for the
      simulation of a heart beat.

PMID- 19162722
TI  - Comparison of analysis techniques of diabetic cardiac action potential
      propagation.
AB  - Diabetes is known to cause a variety of cardiovascular complications. One of the
      effects of the diabetic state is that the conduction velocity of the action
      potential front may be delayed in the myocardium. Current methods of measuring
      this effect have included optical mapping methods, from which the time required
      for activation of the ventricular surface can be measured. It has been proposed
      that the same information could be obtained from the ECG. This paper examines
      whether the current optical methods correlate with the proposed ECG-based method.
      To do this, an ECG measurement algorithm was written and results compared to
      those of the optical method. The data suggest that the new ECG method is
      correlated with the existing optical methods. However, the data also suggest that
      this correlation is highest when the measurement is made during sinus rhythm,
      rather than in response to a pacing stimulus.

PMID- 19162723
TI  - A computer simulation of clinical Electrophysiological Study.
AB  - We present a computer simulation of Electrophysiological Study (EPS) using a
      heart model. In this simulation, standard pacing protocols as used in the
      clinical EPS, including the atrial extrastimulation, ventricular
      extrastimulation, incremental atrial pacing, and incremental ventricular pacing,
      were developed in the heart model. The corresponding excitation and propagation
      process of the heart, and the intracardiac electrograms that would be measured
      with catheter electrodes were computed. We successfully reproduced the EPS tests
      with the heart model. Typical results included the determination of the
      refractory period, induction and termination of supraventricular tachycardias,
      and the localization of accessory pathway by using the heart model of the Wolff
      Parkinson-White (WPW) syndrome of type A. We believe this study shows one of the
      latest progresses in application of whole-heart modeling and computer simulation
      of electrocardiology.

PMID- 19162724
TI  - Usage of cardiac simulation results in source localization of focal epicardial
      arrhythmias using statistical estimation.
AB  - Mapping of the epicardium is possible with the usage of multielectrode venous
      catheters; however, most of epicardial surface is still inaccessible. To overcome
      this problem a method called statistical estimation was proposed, in which the
      relationship between catheter measurements and the remaining sites are created
      from previously obtained high resolution maps, called the training set. Thus,
      there is a need for the acquisition of high resolution epicardial maps from
      patients during open-chest procedures. In this study we hypothesize that
      epicardial maps created from computer simulations might be used in combination
      with maps from patients, so that the need for data acquisition during open-chest
      procedures would be reduced. We used high-resolution epicardial activation maps
      acquired from 13 dog heart experiments, 470 maps from 12 experiments (training
      set) and 50 maps from a separate experiment (test set). Hearts were paced from
      sites regularly distributed over the epicardium. The simulations of focal
      arrhythmias originating from epicardium were performed using a modified version
      of FitzHugh-Nagumo cardiac model within the ventricles of the Auckland canine
      heart model. We registered the experimental and simulation heart geometries using
      iterative closest-points algorithm and procrustes method. We started simulations
      from sites that corresponded to the pacing sites on the experimental geometry and
      created a simulated activation map database (470 maps) and compared the
      simulation results with the corresponding experimental maps. Finally, we
      performed the statistical estimation on the test set by adjusting the content of
      the training set in such a way that simulated maps constituted 100%, 75%, 50%,
      25%, and 0% of the training set. Mean correlation coefficient (CC) between the
      simulated and experimental activation maps was 0.88. Mean CC and the arrhythmia
      source localization error worsened only from 0.93 to 0.92, and 9.65 mm to 12.14
      mm when simulated activation maps constituted 50% of the training set. This study
      showed the feasibility of including cardiac simulation results in the training
      set for source localization of focal epicardial arrhythmias using statistical
      estimation.

PMID- 19162725
TI  - Simulating the effects of atrial fibrillation induced electrical remodeling: a
      comprehensive simulation study.
AB  - Mechanisms underlying atrial fibrillation (AF) are poorly understood. In this
      study, we computationally evaluated the functional roles of AF induced electrical
      remodeling (AFER) on atrial electrical excitations. Experimental data of AFER on
      human atrial myocytes were incorporated into a biophysically detailed model of
      human atrial cells to simulate the effects of AFER at cellular and tissue levels.
      Our results show that AFER dramatically abbreviated atrial action potential
      duration (APD90) and effective refractory period that were quantitatively
      consistent with experimental data. A typical feature of loss in rate dependent
      accommodation of APD90 was observed. AFER slowed down atrial conduction velocity,
      but facilitated atrial conduction at high excitation rates. AFER increased
      tissue's spatial vulnerability for initiation and maintenance of AF remarkably.
      The overall susceptibility of human atrium to arrhythmia was increased. Most
      importantly AFER increased the stability of reentrant waves in 2D and 3D models
      prolonging their lifespan. While reentrant excitation waves self-terminated under
      Control conditions, the same became persistent or degenerated into multiple
      wavelets leading to spatio-temporal chaos under AFER conditions with accelerated
      re-entrant excitation rates. There was an increase in dominant frequency. In
      conclusion, our simulations substantiated a link between AFER and persistence of
      AF, providing mechanistic insights towards better understanding of "AF begets
      AF".

PMID- 19162726
TI  - Development of a new arbitrary waveform defibrillator for cardiac
      electrophysiology research.
AB  - The innovative arbitrary waveform defibrillator for animal research presented in
      this paper is based on two power linear amplifiers in bridge configuration. It is
      capable of delivering 10 J shocks of arbitrary shape and duration. The system can
      be used to test new waveforms by comparing them to traditional ones, in in-vitro
      experiments. The system is battery operated, has an isolated output, and is PC
      controlled. Loads with impedance ranging from 10 to 25 ohms can be connected. A
      maximum of +/-130 V, 10A can be delivered to the loads. Effective voltage and
      current are measured and collected in the PC. Examples of waveforms as well as
      preliminary results from experiments of isolated rabbit hearts are presented.

PMID- 19162727
TI  - RR interval analysis for detection of Atrial Fibrillation in ECG monitors.
AB  - We investigate two RR irregularity measures suitable for Atrial Fibrillation
      (AFIB) detection in ECG monitors, one based on the absolute deviation and the
      other based on the difference between successive RR intervals. A sequence of RR
      intervals is fed to the irregularity measures after applying certain constraints
      on length and beat classifications to provide criteria for detection of AFIB.
      Receiver Operating Curves (ROC) are used to analyze and compare the performance
      of the two methods against MIT-BIH Arrhythmia Database, MIT-BIH AFIB Database and
      a proprietary AFIB Database.

PMID- 19162728
TI  - Model study of imaging myocardial infarction by intracardiac electrical impedance
      tomography.
AB  - Electrical impedance tomography (EIT) detects tissue composition inside a medium
      by determining its resistive properties, and uses various electrode
      configurations to pass a small electric current and measure corresponding
      potential. We investigated the feasibility of reconstructing scarred tissue
      inside the heart wall by employing EIT on the basis of a catheter carrying a
      plurality of electrodes and placed inside the blood-filled heart cavity. We built
      a computer model of the biological medium, and reconstructed the resistivity
      distribution using the finite element method and Tikhonov regularization. The
      results established the successful implementation of the numeric methods and the
      possibility of localizing and quantifying scarred myocardium. Novel application
      of EIT from inside the heart cavity could be useful during catheterization and
      may complement other diagnostic modalities. Further research is necessary to
      assess the impact of several factors on the accuracy of the reconstruction and
      include number of electrodes, catheter location, and scar size.

PMID- 19162729
TI  - A simplified model for lysogenic regulation through DNA looping.
AB  - The lysogenic state of bacteriophage lambda has been a key model for
      understanding gene regulation. A single protein, CI repressor, maintains this
      state by blocking gene expression from two promoters separated by approximately
      2.3 kbp of DNA. CI controls its own expression by positive and negative feedback
      by binding to OR to regulate the PRM promoter. Not only does CI interact directly
      with operator DNA, but CI tetramers bound to OL and OR can form an octamer,
      looping the DNA that lies between them. Previous studies show that OL can assist
      with negative regulation of PRM, and we recently showed that DNA looping can also
      enhance looping activation. In this paper we present a new interpretation of our
      recent experimental data based a new crystal structure of CI. The simpler model
      suggested by the new structural information predicts that the most common forms
      of the DNA loop have similar activation behavior, and are enhanced approximately
      2.2-fold relative to unlooped activation.

PMID- 19162730
TI  - Stochastic probability landscape model for switching efficiency, robustness, and
      differential threshold for induction of genetic circuit in phage lambda.
AB  - The genetic switch of phage lambda provides a paradigm for studying developmental
      biology and cell fate. Although there have been numerous experimental and
      theoretical studies, the mechanisms for switching efficiency, stability and
      robustness, maintenance of lysogenic state, and the induction lytic state are not
      fully understood. In this paper, a new method is adopted to account for the full
      stochasticity typical in small copy events and the exact steady state probability
      landscape of the genetic circuit of the switch network is computed. The stability
      and sensitivity of phage lambda switch and its robustness against perturbations
      derived from our model for wild type and mutants are consistent with experimental
      data. Our study has revealed likely mechanism of the phage switch network that
      was previously unknown.

PMID- 19162731
TI  - A real-time virtual integration environment for the design and development of
      neural prosthetic systems.
AB  - We have developed a virtual integration environment (VIE) for the development of
      neural prosthetic systems. The VIE is a software environment that modularizes the
      core functions of a neural prosthetic system--receiving signals, decoding signals
      and controlling a real or simulated device. Complete prosthetic systems can be
      quickly assembled by linking pre-existing modules together through standard
      interfaces. Systems can be simulated in real-time, and simulated components can
      be swapped out for real hardware. This paper is the first of two companion papers
      that describe the VIE and its use. In this paper, we first describe the
      architecture of the VIE and review implemented modules. We then describe the use
      of the VIE for the real-time validation of neural decode algorithms from pre
      recorded data, the use of the VIE in closed loop primate experiments and the use
      of the VIE in the clinic.

PMID- 19162732
TI  - Extracting alpha band modulation during visual spatial attention without
      flickering stimuli using common spatial pattern.
AB  - In this paper, alpha band modulation during visual spatial attention without
      visual stimuli was focused. Visual spatial attention has been expected to provide
      a new channel of non-invasive independent brain computer interface (BCI), but
      little work has been done on the new interfacing method. The flickering stimuli
      used in previous work cause a decline of independency and have difficulties in a
      practical use. Therefore we investigated whether visual spatial attention could
      be detected without such stimuli. Further, the common spatial patterns (CSP) were
      for the first time applied to the brain states during visual spatial attention.
      The performance evaluation was based on three brain states of left, right and
      center direction attention. The 30-channel scalp electroencephalographic (EEG)
      signals over occipital cortex were recorded for five subjects. Without CSP, the
      analyses made 66.44 (range 55.42 to 72.27) % of average classification
      performance in discriminating left and right attention classes. With CSP, the
      averaged classification accuracy was 75.39 (range 63.75 to 86.13) %. It is
      suggested that CSP is useful in the context of visual spatial attention, and the
      alpha band modulation during visual spatial attention without flickering stimuli
      has the possibility of a new channel for independent BCI as well as motor
      imagery.

PMID- 19162733
TI  - Channel selection by genetic algorithms for classifying single-trial ECoG during
      motor imagery.
AB  - The classification performance of a brain-computer interface (BCI) depends
      largely on the methods of data recording and feature extraction. The
      electrocorticogram (ECoG)-based BCIs are a BCI modality that has the potential to
      achieve high classification accuracy. This paper proposes a new algorithm for
      classifying single-trial ECoG during motor imagery. The optimal channel subsets
      are first selected by genetic algorithms from multi-channel ECoG recordings, then
      the power features are extracted by common spatial pattern (CSP), and finally
      Fisher discriminant analysis (FDA) is used for classification. The algorithm is
      applied to Data set I of BCI Competition III and the classification accuracy of
      90% is achieved on test set by using only seven channels.

PMID- 19162735
TI  - Motor prediction in Brain-Computer Interfaces for controlling mobile robots.
AB  - EEG-based Brain-Computer Interface (BCI) can be regarded as a new channel for
      motor control except that it does not involve muscles. Normal neuromuscular motor
      control has two fundamental components: (1) to control the body, and (2) to
      predict the consequences of the control command, which is called motor
      prediction. In this study, after training with a specially designed BCI paradigm
      based on motor imagery, two subjects learnt to predict the time course of some
      features of the EEG signals. It is shown that, with this newly-obtained motor
      prediction skill, subjects can use motor imagery of feet to directly control a
      mobile robot to avoid obstacles and reach a small target in a time-critical
      scenario.

PMID- 19162734
TI  - The use of a virtual integration environment for the real-time implementation of
      neural decode algorithms.
AB  - We have developed a virtual integration environment (VIE) for the development of
      neural prosthetic systems. This paper, the second of two companion articles,
      describes the use of the VIE as a common platform for the implementation of
      neural decode algorithms. In this paper, a linear filter decode and a recursive
      Bayesian algorithm are implemented as separate signal analysis modules of the VIE
      for the real-time decode of end effector trajectory. The process of implementing
      each algorithm is described and the real-time behavior as well as computational
      cost for each algorithm is examined. This is the first report of the real-time
      implementation of the Mixture of Trajectory Models decode [10]. These real-time
      algorithms can be easily interfaced with pre-existing modules of the VIE to
      control simulated and real devices.

PMID- 19162736
TI  - Unsupervised brain computer interface based on inter-subject information.
AB  - This paper presents an unsupervised subject modeling technique and its
      application to a P300-based word speller. Due to EEG variations across subjects,
      a special training procedure is required to learn a subject-specific
      classification model (SSCM). To deal with the inter-subject variation, we first
      study a subject independent classification model (SICM) that is learned from EEG
      of a pool of subjects. Next we further adapt the SICM by learning from a subset
      of the pooled EEG that is automatically selected based on its similarity to the
      EEG of a new subject. Experiments over ten healthy subjects show that the SICM
      learned from all pooled EEG outperforms the cross-subject models greatly. More
      importantly, the adapted SICM achieves virtually the same performance as the
      SSCM, hence removing the complicated and tedious training procedure.

PMID- 19162737
TI  - A brain-computer interface (BCI) system based on auditory stream segregation.
AB  - An auditory brain-computer interface (BCI) which detected event-related potential
      (ERP) elicited by selective attention to one of the tone streams was proposed.
      Each tone in two kinds of frequency oddball tone sequences with different tone
      frequency range was presented alternatively to subjects, and they were perceived
      by subjects as two kinds of segregated streams. Event-related potentials elicited
      by two kinds of deviant tones were classified by linear discriminant analysis
      (LDA) to find which streams subjects paid selective attention. By the experiments
      to six subjects, it was shown that this system could realize binary selection
      from two kinds of segregated tone streams.

PMID- 19162738
TI  - BMI cyberworkstation: enabling dynamic data-driven brain-machine interface
      research through cyberinfrastructure.
AB  - Dynamic data-driven brain-machine interfaces (DDDBMI) have great potential to
      advance the understanding of neural systems and improve the design of brain
      inspired rehabilitative systems. This paper presents a novel cyberinfrastructure
      that couples in vivo neurophysiology experimentation with massive computational
      resources to provide seamless and efficient support of DDDBMI research. Closed
      loop experiments can be conducted with in vivo data acquisition, reliable network
      transfer, parallel model computation, and real-time robot control. Behavioral
      experiments with live animals are supported with real-time guarantees. Offline
      studies can be performed with various configurations for extensive analysis and
      training. A Web-based portal is also provided to allow users to conveniently
      interact with the cyberinfrastructure, conducting both experimentation and
      analysis. New motor control models are developed based on this approach, which
      include recursive least square based (RLS) and reinforcement learning based
      (RLBMI) algorithms. The results from an online RLBMI experiment shows that the
      cyberinfrastructure can successfully support DDDBMI experiments and meet the
      desired real-time requirements.

PMID- 19162739
TI  - Evaluating the performance of a self-paced BCI with a new movement and using a
      more engaging environment.
AB  - In previous studies, we proposed a self-paced brain computer interface (SBCI)
      system that employed three neurological phenomena to identify intentional control
      (IC) commands from the no control (NC) states of EEG signals. We showed that this
      SBCI system achieved a good performance that was better than those of other EEG
      based SBCI systems. In this paper, we carry out a new study to show that this
      system can be generalized. Specifically, we show that it can also achieve good
      performance when 1) a new type of movement is used (hand extension vs. the finger
      flexion this system was designed for), and 2) NC data are recorded in an engaging
      environment. A more reliable artifact monitoring system is also added to the
      system to rule out not only the effects of eye blinks but also the frontalis
      muscles when controlling the system. Using the data from five participants it is
      shown that the system obtains good performance compared to other EEG-based SBCI
      systems.

PMID- 19162740
TI  - Possibility of reinforcement learning based on event-related potential.
AB  - We applied event-related potential (ERP) to reinforcement signals that are
      equivalent to reward and punishment signals.We conducted an electroencephalogram
      (EEG) in which volunteers identified the success or failure of a task. We
      confirmed that there were differences in the EEG depending on whether the task
      was successful or not and suggested that ERP might be used as a reward of
      reinforcement leaning. We used a support vector machine (SVM) for recognizing the
      P300. We selected the feature vector in SVM that was composed of averages of each
      50 ms for each of the six channels (C3,Cz,C4,P3,Pz,P4) for a total of 700 ms. We
      can suggest that reinforcement learning using P300 can be performed accurately.

PMID- 19162741
TI  - Visual P300-based BCI to steer a wheelchair: a Bayesian approach.
AB  - This paper presents a new P300 paradigm for brain computer interface. Visual
      stimuli consisting of 8 arrows randomly intensified are used for direction target
      selection for wheelchair steering. The classification is based on a Bayesian
      approach that uses prior statistical knowledge of target and non-target
      components. Recorded brain activity from several channels is combined with a
      Bayesian sensor fusion and then events are grouped to improve event detection.
      The system has an adaptive performance that adapts to user and P300 pattern
      quality. The classification algorithms were obtained offline from training and
      then validated offline and online. The system achieved a transfer rate of 7
      commands/min with 95% false positive classification accuracy.

PMID- 19162742
TI  - Improving the performance of brain-computer interface through meditation
      practicing.
AB  - Cognitive tasks using motor imagery have been used for generating and controlling
      EEG activity in most brain-computer interface (BCI). Nevertheless, during the
      performance of a particular mental task, different factors such as concentration,
      attention, level of consciousness and the difficulty of the task, may be
      affecting the changes in the EEG activity. Accordingly, training the subject to
      consistently and reliably produce and control the changes in the EEG signals is a
      critical issue in developing a BCI system. In this work, we used meditation
      practice to enhance the mind controllability during the performance of a mental
      task in a BCI system. The mental states to be discriminated are the imaginative
      hand movement and the idle state. The experiments were conducted on two groups of
      subject, meditation group and control group. The time-frequency analysis of EEG
      signals for meditation practitioners showed an event-related desynchronization
      (ERD) of beta rhythm before imagination during resting state. In addition, a
      strong event-related synchronization (ERS) of beta rhythm was induced in
      frequency around 25 Hz during hand motor imagery. The results demonstrated that
      the meditation practice can improve the classification accuracy of EEG patterns.
      The average classification accuracy was 88.73% in the meditation group, while it
      was 70.28% in the control group. An accuracy as high as 98.0% was achieved in the
      meditation group.

PMID- 19162743
TI  - Simultaneous detection method of P300 event-related potentials and eye gaze point
      using multi-pseudorandom and flash stimulation for brain computer interface.
AB  - A method for simultaneous detecting of P300 response and eye gaze point using
      visual evoked potentials (VEPs) elicited by multi-pseudorandom and flash stimuli
      was examined. Prototype system which would be a practical brain computer
      interface is established and evaluated. Visual stimuli consisted of six small
      squares (visual angle of 0.7x0.7 deg) surrounded by frames/a frame (2x2 deg).
      Squares were flashed with an interval of 180 ms to elicit event-related potential
      of P300, and luminance of each frame was modulated, based on pseudorandom binary
      sequences (PRBS) of 10.23 seconds. Six visual stimuli were simultaneously
      presented on the monitor and subjects were instructed to focus attention
      successively on an appointed square and EEG was recorded during this task. The
      cross correlation functions (kernels) of EEGs and each PRBS were calculated and
      used to determine the subject gazed target. Clear P300 and kernel response for
      target were simultaneously detected, indicating that this technique could be
      useful as a practical brain computer interface system.

PMID- 19162744
TI  - Development of a compact mock circulation system and a new flow-cell model for
      pulse spectrophotometry.
AB  - We have developed an extremely compact mock circulation system. This system can
      simulate artery blood circulation and generate a pulse wave with a very small
      amount of blood. We were also able to measure the in vitro pulsatile optical
      density ratio (Phivt) using this system with a flow cell [1]. Results showed a
      difference between Phivt and the in vivo pulsatile optical density ratio (Phivi)
      for the same oxygen saturations. To explain this difference, we proposed a new
      flow-cell model that includes venous flow and arterial flow. Because these
      systems can simulate the in vivo environment with very accurately, they can be
      applied to various pulse spectrophotometry studies. Moreover, the required blood
      volume is very small so the system can evaluate artificial blood or artificial
      red cells at very low cost. Thus, this system can reduce the time and cost of
      developing new pulse photometry techniques and other medical equipment.

PMID- 19162745
TI  - Non-invasive measurement of Valsalva-induced hemodynamic changes on a bathroom
      scale ballistocardiograph.
AB  - Unobtrusive and compact methods for monitoring time varying hemodynamic trends
      can allow physicians to monitor heart failure of outpatients at home. In this
      paper, the ballistocardiogram (BCG), measured on a modified commercial bathroom
      scale, is proposed as a viable option for this important need. The BCG measures
      the reaction force of the body to cardiac ejection of blood and is a non-invasive
      tool for evaluating cardiovascular function. The Valsalva maneuver was used to
      modulate the hemodynamics in a well documented manner, and BCG signals were
      acquired from 15 subjects. The electrocardiogram (ECG) was simultaneously
      obtained to measure the electrical to mechanical delay in ventricular
      contraction: the interval from the ECG R-wave peak to the BCG J-wave peak. This
      interval, called the RJ interval, decreased for all subjects following the
      release of intrathoracic strain compared to the resting value, suggesting that it
      is inversely correlated to cardiac contractility. The power spectrum magnitude of
      the BCGs showed that the high frequency content increased after release, also
      consistent with increased contractility (faster ejection). Additionally, J-wave
      amplitudes increased following release, suggesting that it is correlated to
      stroke volume. Since RJ interval computation required the ECG, BCG J-wave rise
      time was proposed as an alternative for evaluating cardiac contractility. The
      correlation between this rise time and RJ interval was high (R2=0.78).

PMID- 19162746
TI  - Experimental sensitivity study of inductive phase shift spectroscopy as non
      invasive method for hypoperfusion vs bleeding volumetric detection in brain.
AB  - Hypoperfusion and bleeding in brain are medical conditions that involve a
      decrease and an increase of the relative amount of blood in tissue respectively.
      Both pathologies result in brain edema. This study evaluates experimentally the
      sensitivity of an induction based non-invasive technique for detection of changes
      of fluid volume through phase shift measurements as a possible method to
      distinguish brain hypoperfusion and bleeding process by volumetric monitoring. An
      induction coil-spherical head model was build and tested. The model involves two
      different diameter coils coaxially centered on a two-compartment glass sphere
      head model centrally placed with respect to the coils. Fluid volumes of
      physiological saline in 1 ml decrement and increments were used to simulate
      different hypoperfusion and bleeding levels respectively. Inductive phase shift
      measurements were measured in a whole bandwidth (1 kHz-1 GHz) by an experimental
      inductive spectrometer. The results show significant phase shift increase as a
      function of frequency and fluid volume in both pathologies simulated. At certain
      frequencies the hypoperfusion and bleeding phase shifts increase run in opposite
      ways. The experiments suggest that the tested technique has the potential to
      distinguish the processes of hypoperfusion and bleeding in brain by non-invasive,
      continuous and volumetric monitoring.

PMID- 19162747
TI  - Detection of subjects with higher self-reporting stress scores using heart rate
      variability patterns during the day.
AB  - Heart rate variability (HRV) has been well established to measure instantaneous
      levels of mental stress. Circadian patterns of HRV features have been reported
      but their use to estimate levels of mental stress were not studied thoroughly. In
      this study, we investigated time dependent variations of HRV features to detect
      subjects under chronic mental stress. Sixty eight subjects were divided into high
      (n=10) and low stress group (n=43) depending on their self-reporting stress
      scores. HRV features were calculated during three different time periods of the
      day. High stress group showed decreased patterns of HRV features compared to low
      stress group. When logistic regression analysis was performed with raw multiple
      HRV features, the classification was 63.2% accurate. A new % deviance score
      reflecting the degree of difference from normal reference patterns increased the
      accuracy to 66.1%. Our data suggested that HRV patterns obtained at multiple time
      points of the day could provide useful data to monitor subjects under chronic
      stress.

PMID- 19162748
TI  - Quantifying time awake posturographically.
AB  - Although sleepiness is a major risk factor in traffic and occupational accidents,
      convenient, quantitative, and commercial sleepiness testing is lacking. The issue
      is relevant to policymakers concerned with legislation for, and surveillance of,
      traffic- and occupational safety. This work suggested and examined posturographic
      sleepiness testing for instrumentation purposes. In 63 subjects--for whom we
      tested balance with a force platform during sustained waking for maximum 36 h-
      sustained waking impaired the balance. The sustained waking explained 60% of the
      diurnal balance variations, whereas the time of day explained 40% of the balance
      variations. The first finding -that balance depends on the subject's time awake
      (TA)- allowed to posturographically estimate the subjects' TA with 86% accuracy
      and 97% precision. Results also show that balance scores tested at 13:30 hours
      serve as a threshold to detect excessive sleepiness. This work provides
      guidelines for a posturographic sleepiness tester.

PMID- 19162749
TI  - Study of biosignal response during acupuncture points stimulations.
AB  - The present study examined the effect of electro-acupuncture stimulation of PC5
      and PC6, acupuncture points located on the pericardium meridian, on
      electroencephalogram (EEG) changes, bioimpedance value, and electrocardiogram
      (ECG) heart rate. The EEGs of the frontal, central, temporal, parietal, and
      occipital lobes were measured. Generally, the EEGs increased at large amplitude
      in the all lobe during electro-acupuncture (EA) stimulation of PC5 and PC6.
      According to the present experiments, after the EA stimulation of PC5, EEG was
      verified to change at an extremely large amplitude in the temporal lobe. A
      comparison of biological active points (BAPs) and non-BAPs in bioimpedance
      measurement experiments revealed that reactance resistance had low-resistance
      characteristics and characteristics frequency had frequency characteristics. The
      ECG heart rate decreased at PC6 and increased at PC5. PC6 therefore may have a
      certain effect on sedation of the human nervous system. We applied CWT to detect
      short-time event and the result image representation of the signal has showed us
      that one can easily find the discontinuity at the time scale representation. The
      results of the present study verified that the EA stimulation of BAPs (PC5, PC6)
      affects EEG, human bioimpedance, and ECG heart rate, and such stimulation may be
      capable of affecting the nervous system.

PMID- 19162750
TI  - A reliability study of the new Back Strain Monitor based on clinical trials.
AB  - A new Back Strain Monitor (BSM) device has been developed in order to measure,
      record and analyze movements of the lower back. The purpose of this study was to
      examine the inter-tester and the intra-tester reliability of the movement
      measurements given by the BSM accelerometers, and compare it with the reliability
      of two other conventional measurement methods: the Double Inclinometer method
      (DI) and the Modified-Modified Schober (MMS) method. The clinical studies
      included 23 participants (16 males, 7 females) with no recent history of lower
      back pain, who wore the device during a combination of different anatomical
      movements (flexion, extension, left lateral flexion and right lateral flexion of
      the lumber spine). The tests were conducted by three therapists (testers). The
      reliability results for the BSM accelerometers clearly outperform the results
      obtained for the DI and the MMS methods. The inter-tester reliability gives the
      Intra-Class Correlation (ICC) value of 0.95 for the BSM flexion, 0.89 for the DI
      flexion and 0.74 for the MMS. The intra-tester reliability gives the ICC value of
      0.99 for BSM flexion, 0.94 for DI flexion and 0.77 for the MMS. The BSM
      accelerometers were highly reliable in assessing back movements, measuring these
      movements with less error than the DI and MMS methods.

PMID- 19162751
TI  - Development of failure detection system based on vibration signal for smart
      artificial heart: in vitro study.
AB  - To realize safe and effective medical treatment for patients with implantable
      artificial hearts, we have developed a smart artificial heart (SAH). The SAH can
      grasp the mechanical condition of the artificial heart and the physiological
      condition of the patient. The purpose of this study is to develop a failure
      detection system based on the vibration signal from artificial heart in order to
      enhance the ability of failure detection for the SAH. We suppose this vibration
      signal reflects not only the mechanical condition of the artificial heart but
      also a part of the physiological condition of the patient. The developed failure
      detection system is composed of a vibration sensor unit and a failure detection
      algorithm. The algorithm has a standard frequency pattern, which is made from the
      vibration signal of good condition of both the artificial heart and patient.
      Observing the difference from the standard frequency pattern, the algorithm
      detects failure conditions. Therefore, this algorithm does not need prior
      knowledge of vibration characteristics corresponding to failures. After
      confirming that the vibration signal are affected by pump speed and pulsation in
      two kinds of mock circulatory loops, we performed thrombogenesis detection by
      using the failure detection system in mock circulatory loop with sheep blood. As
      a result, this system indicated a possibility of detecting the initial sign of
      thrombogenesis earlier than current signal. In conclusion, we think that this
      failure detection system can cooperate with other sensor systems of the SAH and
      enhance the ability of failure detection for the SAH.

PMID- 19162752
TI  - The effect of surface neuromuscular electrical stimulation and compression
      hosiery applied to the lower limb, on the comfort and blood flow of healthy
      subjects.
AB  - Chronic venous insufficiency (CVI) is a severe disease affecting the venous
      system of the lower limbs. Compression therapy aims to counteract the venous
      hypertension caused by CVI. However, in spite of significant advances in
      compression treatments in recent years, CVI and its associated diseases are
      frequently characterized by slow healing rates and a need for more aggressive
      therapies such as surgery. Surface neuromuscular electrical stimulation (SNMES)
      offers potential benefits when used in conjunction with compression therapy by
      increasing venous return through muscular compression of the calf muscles. In
      order to assess the long term feasibility of SNMES with compression hosiery as a
      treatment modality for CVI, it is necessary to evaluate the effects of such a
      treatment on subject blood flow and comfort levels. This paper presents the
      results of a study investigating the effects of long term SNMES and compression
      hosiery applied to the lower limb, in the comfort and blood flow of healthy
      subjects.

PMID- 19162753
TI  - A target control Infusion method for neuromuscular blockade based on hybrid
      parameter estimation.
AB  - The paper presents a new method for target control infusion (TCI) for
      neuromuscular blockade (NMB) level control of patients subject to general
      anaesthesia. The method combines an inversion of the
      pharmacokinetic/pharmacodynamic (PK/PD) model with a hybrid parameter estimation
      method that uses on-line data from the initial bolus response to estimate the
      model parameters. Although atracurium is considered as relaxant, the newly
      proposed method may be applied to other drugs for which the PK/PD model is
      available. Simulation results on a bank of 100 patient models are presented to
      demonstrate the achievable performance.

PMID- 19162754
TI  - Sensorless control for a sophisticated artificial myocardial contraction by using
      shape memory alloy fibre.
AB  - The authors have been developing an artificial myocardium, which is capable of
      supporting natural contractile function from the outside of the ventricle. The
      system was originally designed by using sophisticated covalent shape memory alloy
      fibres, and the surface did not implicate blood compatibility. The purpose of our
      study on the development of artificial myocardium was to achieve the assistance
      of myocardial functional reproduction by the integrative small mechanical
      elements without sensors, so that the effective circulatory support could be
      accomplished. In this study, the authors fabricated the prototype artificial
      myocardial assist unit composed of the sophisticated shape memory alloy fibre
      (Biometal), the diameter of which was 100 microns, and examined the mechanical
      response by using pulse width modulation (PWM) control method in each unit. Prior
      to the evaluation of dynamic characteristics, the relationship between strain and
      electric resistance and also the initial response of each unit were obtained. The
      component for the PWM control was designed in order to regulate the myocardial
      contractile function, which consisted of an originally-designed RISC
      microcomputer with the input of displacement, and its output signal was
      controlled by pulse wave modulation method. As a result, the optimal PWM
      parameters were confirmed and the fibrous displacement was successfully regulated
      under the different heat transfer conditions simulating internal body temperature
      as well as bias tensile loading. Then it was indicated that this control theory
      might be applied for more sophisticated ventricular passive or active restraint
      by the artificial myocardium on physiological demand.

PMID- 19162755
TI  - An electronic implant for Hydrocephalus therapy assistance.
AB  - A device intended to measure acceleration and pressure across a conventional
      valve of a shunt implant was designed and built. In this model, sensory data is
      sent wirelessly from the implant to a monitor, where proper evaluation algorithms
      detect the instantaneous valve status (open/close) and the intracranial pressure.
      Clinical implementation of this concept will potentially become a great step
      forward in diagnostics and treatment of Hydrocephalus.

PMID- 19162756
TI  - Isothermic vs thermoneutral hemodiafiltration evaluation by indirect calorimetry.
AB  - HD and HDF as hemodialytic therapies normally alter patient's haemodynamic
      stability, due to the inflammatory response to extracorporeal blood circuit,
      producing increment of the core temperature (+1.0 degrees C). However, such
      increase in temperature could be controlled by lowering dialysate's temperature
      using two main modalities techniques (isothermic and thermoneural) with different
      patient's thermal balance consequences, not yet well studied. In this work,
      energy expenditure (EE) was measured by indirect calorimetry in a group of 12
      patients waiting kidney transplant. In each patient, EE was assessed (as a power
      generation) during isothermic and thermoneutral modalities as a manner of cross
      and prospective study (a) at before therapy, (b) during therapy and (c) at the
      end of the HDF therapy. Wheraeas, power extraction was measured by a BTM (Blood
      Temperature Monitor from Fresenius Inc) in order to determine power balance in a
      thermodynamic model of the extracorporeal circuit. The results showed significant
      differences in the power balance when EE at during therapy was subtracted from
      the EE at before therapy. Then, EE increments were 32 Kcal/4-hours during
      isothermic and 3.6 Kcal/4-hours during thermoneutral HDF sessions (p<0.05).
      While, BTM totals power extraction was 91 and 16.1 Kcal/4-hours (p<0.05),
      respectively. Additionally, it was estimated a 12% of EE/day increment during HDF
      isothermic at during therapy stage compared with none significative EE increment
      during thermoneutral modality. The statistical evidence confirmed the expected
      hypothesis that both modalities affect in different manner the patient's EE.
      Also, we conclude there is no satisfactory data interpretation when the
      thermodynamic model was applied expecting null balance between EE increment and
      BTM power extraction. Therefore, these findings force to think there is need of
      different BTM design and measurement setting with ability to follow dynamic
      patient's EE changes with the purpose to achieve a better power balance.

PMID- 19162757
TI  - Skin stimulation by the fluid powered self-excited oscillation and its effect on
      the human body.
AB  - A novel fluid power actuator called Flat Ring Tube (FRT) is introduced in this
      paper. The mechanism of FRT is so simple that it only needs a urethane flat tube
      and water pressure power source. No valves or switches are required. Applying
      constant water pressure results in periodic oscillation of the tube. The
      frequency is proportional to the flow rate of water and inversely proportional to
      the tube length. By contacting the tube with a passively supported shaft, it
      rotates due to the periodic tube oscillation. This principle can also generate
      the linear driving force, when FRT is mounted so as to kick the ground. Such kind
      of performance can be also expected to stimulate the blood flow rate, when FRT
      touches on the skin of the human body appropriately. The experimental results
      showed us the developed wearable massage device could effectively improve both
      the circulation of the blood flow and the density of oxygen in blood, which
      resulted in let the people feel more comfortable than conventional massage
      devices.

PMID- 19162758
TI  - Training for knee injury prevention using a pivoting elliptical machine.
AB  - Anterior cruciate ligament (ACL) is the most commonly injured knee ligament in
      sports-related activities, especially in pivoting sports. In general, knee joint
      movements about the off-axes are much more limited and musculoskeletal injuries
      are usually associated with excessive loading/movement about the off-axes. The
      purposes of this project were to develop an injury prevention program including a
      pivoting elliptical exercise machine to address the specific ACL injury
      mechanisms, especially in women. ACL injury prevention training was carried out
      to target the specific injury mechanisms associated with tibial rotation. The
      pivoting elliptical training improved the off-axis neuromuscular control
      considerably. Training-induced neuromuscular changes in tibial rotation were
      assessed with multiple outcome measures.

PMID- 19162759
TI  - Swallow stent with hyperthermia function.
AB  - An operation of an esophagus cancer is one of the most difficult operations even
      now, when medicine progressed. One of the most important points is the
      difficulties of esophagus reconstruction. In an operation, since the stomach and
      intestines are used as a substitute, an invasion becomes large and an operation
      of elderly people becomes difficult. Although the improvement in a life prognosis
      is expected if cancer is removable, there are a lot of cases, who were too late
      for surgery of the esophageal cancer at the time of diagnosis. Then, a Swallow
      Stent with Hyperthermia function for the terminal esophageal cancer patients, for
      whom an operation cannot be conducted, was invented. The Swallow Stent with
      Hyperthermia function has three characteristics. 1. Completely noninvasive, 2.
      Hyperthermia on the carcinoma tissue. 3. Swallow function. Possibilities are
      expected as one of the alternative candidates for a terminal esophagus cancer
      therapy.

PMID- 19162760
TI  - Fabrication of new Magnetic Micro-Machines for minimally invasive surgery.
AB  - Magnetic Micro-Machines (MMM) have been proposed as effective tools for minimally
      invasive surgery. We propose an innovative and low cost MMM manufacturing process
      based on casting of a mixture of SmCo powders and acrylic resin into silicone
      moulds. After developing a MMM prototype, we tested its swimming ability by using
      different siliconic oils of known kinematic viscosity. The propulsion efficiency,
      given by the velocity and frequency ratio, has been found comparable with other
      MMM reported in the literature.

PMID- 19162761
TI  - Using HSPA to improve the telemedical links on a moving ambulance.
AB  - As the demand for faster and more effective health care increases, there is a
      growing need to establish mobile, high-speed communications between a moving
      ambulance and a consultation point (usually a hospital). The recent addition of
      HSPA (HSDPA and HSUPA) into the UMTS suite provides higher bandwidth and reduced
      delays, making this choice ideal for real-time telemedical applications. In this
      paper, we will describe a set of scenarios that took place in a typical large
      city area, along with their equivalent results: a moving ambulance was linked
      with a consultation station using HSPA and several videoconferencing sessions
      were initiated. Best-case, worst-case and average scenarios were recorded.
      Furthermore, in areas where the UMTS reception was marginal, a repeater was
      placed on top of the vehicle to boost up the signal power and thus maintain the
      higher bandwidth. Finally, treating doctors were asked to evaluate the
      effectiveness of this system's outputs, based on a variety of objective and
      subjective criteria.

PMID- 19162762
TI  - Implementation of an integrated drug information system for inpatients to reduce
      medication errors in administering stage.
AB  - In hospitals, computerized provider order entry (CPOE) with Clinical Decision
      Support System (CDSS) would decrease respectable amount of medication errors in
      prescribing stage. However, medication errors occur not only in prescribing
      stage, but also in administering stage. In this study we constructed an
      integrated drug information system (IDIS) for inpatients. To reduce medication
      errors in administering stage, IDIS is constructed on a computerized drug cart
      and could provide patients' data, drug information with drug images, drug
      administration routes, drug interactions, and intravenous drug compatibility
      information. By offering these helpful information, care workers in Taiwan could
      easily find medication errors as well. IDIS have been constructed and been
      demonstrated by patients' information from a medical center in Taipei. The
      primary results showed that 16.3% of inpatients still had drug interaction
      concerns, i.e. every patient suffered approximately 0.35 drug interaction in
      average. It seems that except for CPOE with CDSSs, it could be helpful using such
      a system to prevent medication errors.

PMID- 19162763
TI  - VolunteerGet--a novel information system for engaging society in volunteering for
      emergency care.
AB  - This work presents VolunteerGet, a novel information system for engaging society
      in volunteering for emergency situations. We will use the social networking and
      location services infrastructure as a means of 1) registering volunteers and
      other users, 2) spreading the word on volunteering opportunities and increasing
      the volunteer database, 3) matching the users and volunteers at time and location
      of need. Such a system has the potential to promote volunteering as a social
      phenomenon and eventually reduce suffering and mortality.

PMID- 19162764
TI  - Unused information: detecting and applying eye contact data in computerized
      healthcare systems.
AB  - Medical computing systems rely primarily on traditional human-computer
      interfaces, such as the keyboard, mouse and touch screen, however future systems
      will incorporate vastly enhanced interaction capabilities. Some of these, such as
      speech control and eye contact sensing, have begun to appear on the medical
      computing landscape. Eye contact provides computer systems with a wealth of yet
      uncollected information about user attention and attentiveness, and may allow for
      personalized interfaces, while requiring almost no training to use. This paper
      introduces an advanced prototype of a gaze-enhanced speech recognition charting
      system for surgical nurses. We go on to discuss the implications of our system
      and of gaze detection in general for medical computing.

PMID- 19162765
TI  - MediNet: personalizing the self-care process for patients with diabetes and
      cardiovascular disease using mobile telephony.
AB  - This paper describes MediNet, a mobile healthcare system that is being developed
      to personalize the self-care process for patients with both diabetes and
      cardiovascular disease. These two diseases were chosen based on their
      interrelationship. Patients with diabetes are at least twice as likely to have
      heart disease or a stroke as compared to persons without diabetes. Furthermore,
      persons with diabetes also tend to develop heart disease or have strokes at an
      earlier age than other people. MediNet uses a reasoning engine to make
      recommendations to a patient based on current and previous readings from
      monitoring devices connected to the patient and on information that is known
      about the patient. It caters for the uniqueness of each patient by personalizing
      its recommendations based on individual level characteristics of the patient, as
      well as on characteristics that groups of patients tend to share.

PMID- 19162766
TI  - Telemedicine network physical connection design for remote areas. Case Baruta--El
      Hatillo.
AB  - The telemedicine has increased mostly over recent years. Especially in developing
      countries where a high proportion of the population lives in rural areas or
      difficult to access. However it is successful implementation is closely connected
      with an appropriate design of the telecommunications network, part essential when
      deploying a network and the selection of appropriate communications technologies,
      realistic and sustainable according to the characteristics of the context in
      which it is deployed. This paper explain the situation of health centers in the
      municipalities Baruta and Hatillo in Venezuela, it proposes the design of a
      telemedicine network to allow interconnect the outpatient units with the referral
      hospital. Then it describes wireless technologies studied and finally it presents
      the entire design process of the network physical connection.

PMID- 19162767
TI  - Performance evaluation of cellular phone network based portable ECG device.
AB  - In this study, cellular phone network based portable ECG device was developed and
      three experiments were performed to evaluate the accuracy, reliability and
      operability, applicability during daily life of the developed device. First, ECG
      signals were measured using the developed device and Biopac device (reference
      device) during sitting and marking time and compared to verify the accuracy of R
      R intervals. Second, the reliable data transmission to remote server was verified
      on two types of simulated emergency event using patient simulator. Third, during
      daily life with five types of motion, accuracy of data transmission to remote
      server was verified on two types of event occurring. By acquiring and comparing
      subject's biomedical signal and motion signal, the accuracy, reliability and
      operability, applicability during daily life of the developed device were
      verified. Therefore, cellular phone network based portable ECG device can monitor
      patient with inobtrusive manner.

PMID- 19162768
TI  - IMS: a new technology to develop a telemedicine system.
AB  - The emergent IMS (Internet Protocol Multimedia Subsystem) technology appears to
      improve the current communication technologies. Its characteristics, such as
      Quality of Service (QoS), make it an advantageous system for innovative
      applications. Providing integrated services to users is one of the main reasons
      for the existence of IMS. Operators provide the technology as an open source, to
      be able to use services developed by researchers. Combining and integrating them,
      users will receive completely new services. Our proposal of use for IMS is the
      development of a telemedicine platform, designed to support not only remote
      biological signal monitoring, but value-added services for diagnosis and medical
      care, both of these working in real time.

PMID- 19162769
TI  - Electronic orthotics shoe: preventing ulceration in diabetic patients.
AB  - The improvement in processor performance through continuous breakthroughs in
      transistor technology has resulted in the proliferation of lightweight embedded
      systems. Advances in wireless technology and embedded systems have enabled remote
      healthcare and telemedicine. Continuous and real-time monitoring can discretely
      analyze how a patient's lifestyle affects his/her physiological conditions and if
      additional symptoms occur under various stimuli. Diabetes is one of most
      difficult challenges facing the healthcare industry today. One of the primary
      afflictions of diabetic patients is peripheral neuropathy (loss of sensation in
      the foot). As a direct result of this condition, the likelihood of ulcer
      increases which in many cases leads to to amputation. We have developed a
      wireless electronic orthotics composed of lightweight embedded systems and non
      invasive sensors which can be used by diabetic patients suffering from peripheral
      neuropathy. Our proposed system monitors feet motion and pressure distribution
      beneath the feet in real-time and classifies the state of the patient. The
      proposed system detects the conditions that could potentially cause a foot ulcer.
      This system enables a continuous feedback mechanism for instance in case of an
      undesired behavior or condition a preemptive message wirelessly to the patient
      and the patient's caregiver.

PMID- 19162770
TI  - Consultation virtual collaborative environment for 3D medicine.
AB  - This article focuses on the problems of consultation virtual collaborative
      environment, which is designed to support 3D medical applications. This system
      allows loading CT/MR data from PACS system, segmentation and 3D models of
      tissues. It allows distant 3D consultations of the data between technicians and
      surgeons. System is designed as three-layer client-server architecture.
      Communication between clients and server is done via HTTP/HTTPS protocol. Results
      and tests have confirmed, that today's standard network latency and dataflow do
      not affect the usability of our system.

PMID- 19162771
TI  - Design of an intelligent and personalised shunting system for hydrocephalus.
AB  - Hydrocephalus is a neurological disease that manifests itself in an elevated
      fluid pressure within the brain, and if left untreated, may be fatal. It is
      currently treated using shunt implants, which consist of a mechanical valve and
      tubes that regulate the pressure of cerebrospinal fluid (CSF) by draining excess
      fluid into the abdomen. Hydrocephalus shunting systems are no longer expected
      simply to regulate the intracranial pressure (ICP), but also to offer the option
      of regaining independence of the shunt. Additionally, they could offer
      personalised valve management which is one of the main limitations of current
      shunts. This paper describes the design of a multi-agent system for an
      intelligent and personalised CSF management system. Patient feedback and
      intracranial pressure readings will play important roles in the process of CSF
      regulation and weaning, introduces an element of personalisation to the
      treatment. The new shunting system would deliver both reactive and goal-driven
      solutions for the treatment, at the same time the intelligent part of the system
      will be monitoring how well the shunt is performing. These tasks can be achieved
      by implementing an agent approach in designing this system. Such system would
      help us to understand more about the dynamics of hydrocephalus.

PMID- 19162772
TI  - 3.5G based mobile remote monitoring system.
AB  - Low bandwidth has long been a reason for the unsuitability of wireless internet
      in telemedicine. However with the advent of extended third generation wireless as
      an economically accessible high speed network, more opportunities are being
      created in this area of telemedicine. This paper explores the opportunity created
      by the latest wireless broadband technology for remote monitoring of patients in
      the home.

PMID- 19162773
TI  - The development of personalised cognitive prosthetics.
AB  - Persons suffering from mild dementia can benefit from a form of cognitive
      prosthetic which can be used to assist them with their day to day activities.
      Within our current work we are aiming to develop a successful user-validated
      cognitive prosthetic for persons with mild dementia. We have devised a three
      phased waterfall methodology to support our developments. Based on the evaluation
      of the first of these phases which involved the processes of user requirements
      gathering, prototype development and evaluation of in situ deployment of the
      technology we have been able to guide the technical development within the second
      phase of our work. Within this paper we provide an overview of the first phase of
      our methodology and demonstrate how we have used the results from this to guide
      the second phase of our work, especially with regards to the notion of
      personalisation.

PMID- 19162774
TI  - Experimental evaluations of wearable ECG monitor.
AB  - Healthcare industry is changing with ubiquitous computing environment and
      wearable ECG measurement is one of the most popular approaches in this healthcare
      industry. Reliability and performance of healthcare device is fundamental issue
      for widespread adoptions, and interdisciplinary perspectives of wearable ECG
      monitor make this more difficult. In this paper, we propose evaluation criteria
      considering characteristic of both ECG measurement and ubiquitous computing. With
      our wearable ECG monitors, various levels of experimental analysis are performed
      based on evaluation strategy.

PMID- 19162775
TI  - STDAS: sensing task and data aggregation scheduling for astronaut health
      monitoring using wireless mesh networks.
AB  - Astronaut health monitoring (AHM) during long durations of space missions will
      play a significant role in mission success. Designing networked healthcare
      systems for aerospace exploration that will enable continual surveillance and
      timely notification of astronaut health information to terrestrial healthcare
      providers at minimal deployment and operation cost is an extremely challenging
      problem. However, such capabilities will enhance the opportunities for remote
      medical assistance during space missions. In this paper, we extend our task and
      data aggregation scheduling from single-hop and multi-hop network to mesh
      network. The algorithm aims to optimize the network performance with respect to
      response time and network delay. The upper and lower bounds are derived to
      provide certain guarantee on data delivery time. The performance of a wireless
      mesh network with 25 sensor nodes is examined by varying network bandwidth and
      sensing power of sensor nodes. Basic recursive equations for sensing and data
      reporting are developed for the case of homogeneous and heterogeneous mesh
      networks and the performance results of two representative data sensing and
      reporting strategies are presented.

PMID- 19162776
TI  - Web-based evaluation of Parkinson's disease subjects: objective performance
      capacity measurements and subjective characterization profiles.
AB  - Parkinson's Disease (PD) is classified as a progressively degenerative movement
      disorder, affecting approximately 0.2% of the population and resulting in
      decreased performance in a wide variety of activities of daily living. Motivated
      by needs associated with the conduct of multi-center clinical trials, early
      detection, and the optimization of routine management of individuals with PD, we
      have developed a three-tiered approach to evaluation of PD and other neurologic
      diseases/disorders. One tier is characterized as 'web-based evaluation',
      consisting of objective performance capacity tests and subjective questionnaires
      that target history and symptom evaluation. Here, we present the initial
      evaluation of three representative, self-administered, objective, web-based
      performance capacity tests (simple visual-hand response speed, rapid alternating
      movement quality, and upper extremity neuromotor channel capacity). Twenty-one
      subjects (13 with PD, 8 without neurologic disease) were evaluated. Generally
      good agreement was obtained with lab-based tests executed with an experienced
      test administrator. We conclude that objective performance capacity testing is a
      feasible component of a web-based evaluation for PD, providing a sufficient level
      of fidelity to be useful.

PMID- 19162777
TI  - Optical scattering as a contrast mechanism in confocal imaging.

PMID- 19162778
TI  - In vivo volumetric blood flow imaging using optical microangiography at capillary
      level resolution.

PMID- 19162779
TI  - Comparison of flow-sound relationship for different features of tracheal sound.
AB  - In recent years, respiratory flow estimation using tracheal sounds has received
      considerable attention. In this paper, four different features of tracheal sound
      are investigated and their relationships with flow at different target flow rates
      are examined during inspiration and expiration phases. The features include
      average power (AvgPwr), logarithm of the variance (LogVar), logarithm of the
      range (LogRng) and logarithm of the envelop (LogEnv) of tracheal sound. For each
      feature a linear model is fitted to the flow and the feature. The results show
      that LogVar is the best feature to describe flow-sound relationship with a linear
      model, while the slope of the linear model using AvgPwr shows the largest
      deviation from a line with changes in target flow rates. Also, the distance from
      origin of the linear model using any feature changes linearly with variations of
      target flow.

PMID- 19162780
TI  - Non-symmetrical double-logistic analysis of 24 hour arterial stiffness profile in
      normotensive and hypertensive subjects.
AB  - OBJECTIVES: Mechanisms underlying the circadian profile of cardiovascular events
      (CE) are not totally understood. Whether circadian changes in arterial stiffness
      (AS) could be related to the circadian profile of CE remains to be investigated.
      As yet, there is no accepted way to measure circadian profiles or nocturnal
      related and/or morning-related changes in cardiovascular variables. The aim of
      this study was to characterize the circadian pattern and day-night and night-day
      changes of AS in untreated hypertensive (HG) and healthy subjects (NG), using a
      recently developed non-symmetrical six-parameter double-logistic model. METHODS:
      Seven hypertensive and seven normotensive subjects underwent 24 hour ambulatory
      recordings of blood pressure (BP), heart rate (HR) and aorto-brachial pulse
      transit time (PTT(AB)) and pulse transit velocity index (PTV(AB)). PTT(AB) and
      PTV(AB) are inversely and directly related to AS, respectively. The circadian
      profile and transitional periods (day-night and night-day) were analyzed using a
      model described by a six-parameter double logistic equation. CONCLUSIONS: The
      model was adequate to characterize the circadian pattern of AS. We provide the
      first evidence that AS in humans follows an asymmetric circadian pattern and that
      this differs between NG and HG. In both NG and HG, AS had a circadian profile,
      with the highest levels in the night. HG showed larger levels of AS, larger BP
      variations and rate of change and minor changes in AS during transitional
      periods.

PMID- 19162781
TI  - A new approach to reconstruction of central aortic blood pressure using
      'adaptive' transfer function.
AB  - This paper presents a new system identification approach to the reconstruction of
      central aortic blood pressure signal by exploiting a non-invasive peripheral
      blood pressure measurement. This technique, which is called the 'adaptive'
      transfer function, is able to reconstruct the aortic blood pressure signal by
      characterizing the aortic-to-peripheral cardiovascular dynamics solely based on
      the peripheral measurement. In contrast to the previous related efforts, it does
      not require any a priori knowledge on the empirical and/or population-based
      relationship, e.g. the predetermined or generalized transfer function, as well as
      multiple peripheral measurements. The initial proof-of-principle on the efficacy
      of the adaptive transfer function is demonstrated by the experimental results
      from human and animal subjects.

PMID- 19162782
TI  - Quantification of forward and backward arterial waves by model-based analysis of
      aortic and femoral artery pressure waveforms.
AB  - We developed a technique to quantify forward and backward arterial waves by model
      based analysis of aortic and femoral artery pressure waveforms. Thus, in contrast
      to conventional techniques, our technique does not require a more difficult
      arterial flow measurement. We validated the forward and backward waves through a
      set of canine experiments by showing that the waves accurately predicted a third
      arterial pressure waveform measurement and changed in the expected manner to
      interventions of known effect. We also calculated the waves during nine different
      hemodynamic conditions. Our results showed that the relative magnitude of the
      backward wave was smallest during nitroglycerin and dobutamine and largest during
      phenylephrine and hemorrhage, while the time delay between the two waves was
      smallest during atrial pacing and about the same during the remaining eight
      conditions.

PMID- 19162783
TI  - User-guided interictal spike detection.
AB  - In the diagnosis and treatment of epilepsy, long-term monitoring may be required
      to document and study interictal activities such as interictal spikes. However,
      visual inspection of the EEG done by an expert is too time consuming and
      researchers normally resort to automatic detection methods. We describe a new EEG
      user-guided interictal spike detection algorithm that only requires the user to
      annotate a few spikes. We use the annotations to build a template that captures
      the relevant features of spikes, and then use Mean Squared Error (MSE) test to
      detect all of the other spikes in the recording. The detected events are rank
      ordered so that the user can easily identify the true spikes and their time of
      occurrence. The true spikes are then annotated to the EEG signals and reported to
      the EEG expert for further evaluation. This design provides a compromise between
      the enormous time commitments necessary to annotate recordings by hand and the
      inability of fully-automatic spike detection algorithms to account for the
      variability between subjects. Because spike morphology and spatial distribution
      change considerably when patients go through cycles of wake and sleep in long
      term monitoring, this detection algorithm uses multichannel multiple templates to
      detect more than one type of event. The algorithm is able to achieve an average
      sensitivity of 96% and an average of 4.8 false detections/ hour.

PMID- 19162784
TI  - Power analysis of gamma frequencies (30 - 47Hz), adjusting for muscle activity
      (80 - 97Hz), in anesthesia: a comparison between young adults, middle-aged and
      the elderly.
AB  - This study looks at the role of EEG gamma activity, and the influence of facial
      EMG (80-97 Hz), in predicting consciousness during anesthesia. It also studies
      the association between the conventional depth of anesthesia index, BIS (Aspect
      Medical Systems), and EEG gamma and EMG activity. Data has been collected from 21
      adult patients and grouped into young adults (18 - 39 yrs, n=3), middle-aged (40 
      64 yrs, n=10) and the elderly (65+ yrs, n=8). The power of the EEG gamma
      activity was recorded from Fpz - Mastoid and the power of the EMG was recorded
      from Fpz - Mastoid and Masseter - Mastoid. It has been found that when considered
      alone, EEG gamma power is associated with both BIS index and consciousness versus
      unconsciousness, showing a decrease in power as consciousness is lost. When the
      effect of EEG gamma power is adjusted for EMG, it is found that generally these
      associations can be explained by the EMG power alone. There are two exceptions to
      this. In the young adults group there is a stronger association between BIS index
      and EEG gamma than there is between BIS index and EMG. In the elderly group, the
      state of consciousness is equally associated with EEG gamma and EMG recorded from
      the Masseter, but not with the EMG recorded from Fpz.

PMID- 19162785
TI  - Contrast enhanced magnetic resonance imaging of the liver.
AB  - Dynamic contrast enhanced magnetic resonance imaging (DCE MRI) is a useful tool
      to characterise and stage a disease. Here we investigate the application of DCE
      MRI to the liver, an organ subject to large excursions during normal breathing.
      For DCE MRI it is important to have an estimate of the longitudinal relaxation
      time parameter T1. We show that by using a T1 mapping approach, which takes into
      account inaccuracies in transmitted flip angles, we obtain a smoother T1 map,
      resulting in a more consistent parameter estimation for the subsequent analysis.
      The dynamic imaging protocol described enables the acquisition of high resolution
      unblurred images by simulating the normal breathing cycle. The contrast enhanced
      data is aligned, first rigidly, then non-rigidly, and input to a two-compartment
      pharmacokinetic model. We observe that rigid registration markedly improves the
      parameter estimation, but is insufficient in clinically important heterogeneous
      areas.

PMID- 19162786
TI  - Dynamic contrast-enhanced MRI of ocular biotransport in normal and hypertensive
      eyes.
AB  - This study aims to employ in vivo dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) to evaluate the ocular transport following an induction of
      ocular hypertension in a rat model of chronic glaucoma. Upon systemic
      administration of Gd-DTPA solution, T1-weighted signal increase was observed in
      the vitreous body of the glaucomatous eye but not the control eye. This increase
      occurred earlier in the anterior vitreous body than the preretinal vitreous.
      Further, there was an earlier Gd-DTPA transport into the anterior chamber in the
      majority of glaucomatous eyes. Our DCE-MRI findings revealed the leakage of Gd
      DTPA at the aqueous-vitreous interface, which was likely resulted from increased
      permeability of blood-aqueous or aqueous-vitreous barrier. These may explain the
      sources of changing biochemical compositions in the chamber components, which may
      implicate the neurodegenerative processes in the glaucomatous visual components.

PMID- 19162787
TI  - Quantitative accuracy of delayed hyperperfusion in MRI of transient ischemia in
      rats.
AB  - A strong hyperperfusion was reported in transient ischemic tissue between 48 and
      72 hours after middle cerebral artery occlusion (MCAO). Cerebral blood flow (CBF)
      estimated by continuous arterial spin labeling (CASL) with short delay after
      tagging was sensitive to cerebral blood volume (CBV) change. The delayed
      hyperperfusion may indicate a CBV increase after MCAO. For confirmation of the
      delayed hyperperfusion, we investigated a transit-time dependency in CASL at two
      days after MCAO. We also acquired CBF using the dynamic susceptibility contrast
      (DSC) at the same day. We have confirmed the CBF in transient ischemic tissue is
      quite higher (179.1+/-21.6 ml/100g/min) than normal tissue (121.0+/-6.9
      ml/100g/min) with CASL using tagging delay of 0.4 sec. CBF estimated by DSC also
      show delayed hyperperfusion in transient ischemic tissue. These results confirm
      existence of physiological delayed hyperperfusion in transient ischemic area.

PMID- 19162788
TI  - Uptake and distribution of gadolinium in the ocular lens.
AB  - The lens of the eye has no blood vessels. Although necessary for transparency,
      this feature of the ocular lens implies that any circulation in the lens tissue
      must be avascular. A range of previous studies attests to the metabolic activity
      of the fiber cells that make up the body of the lens. It is also established that
      the continuing transparency of the lens depends upon this metabolic activity.
      When metabolism is disturbed, cataracts (lens opacities) result. It has been
      proposed that metabolism occurs throughout the lens, enabled by an intercellular
      micro-circulation system driven by ion pumps and cell volume-regulation
      mechanisms. The present study attempted directly to trace micro-circulation in
      the ocular lens on a spatially coarse scale. High field strength magnetic
      resonance imaging was used to record the movement of gadolinium into the lens and
      the global distribution patterns that result. Our data lend new support to
      previous attempts at documenting, by other techniques, differential micro
      circulation mechanisms in the ocular lens.

PMID- 19162789
TI  - A new denoising method for dynamic contrast-enhanced MRI.
AB  - This paper presents a new algorithm for denoising dynamic contrast-enhanced (DCE)
      MR images. The algorithm is called Dynamic Non-Local Means and is a novel
      variation on the Non-Local Means (NL-Means) algorithm. It exploits the redundancy
      of information in the DCE-MRI sequence of images. An evaluation of the
      performance of the algorithm relative to six other denoising algorithms-Gaussian
      filtering, the original NL-Means algorithm, bilateral filtering, anisotropic
      diffusion filtering, the wavelets adaptive multiscale products threshold method,
      and the traditional wavelet thresholding method-is also presented. The evaluation
      was performed by two groups of expert observers-18 signal/image processing
      experts, and 9 clinicians (8 radiographers and 1 radiologist)-using real DCE-MRI
      data. The results of the evaluation provide evidence, at the alpha=0.05 level of
      significance, that both groups of observers deem the DNLM algorithm to perform
      visually better than all of the other algorithms.

PMID- 19162790
TI  - Assessment of vessel size by MRI in an orthotopic model of human pancreatic
      cancer.
AB  - Pancreatic cancer is a devastating disease with no cure. Therapies that target
      the tumor vasculature are promising new treatment strategies. Magnetic resonance
      imaging (MRI) can non-invasively determine a vessel size index and a blood volume
      fraction to characterize the vascular compartment in a tumor. The changes in the
      T2 and T2* relaxation rate constants after the administration of
      superparamagnetic iron oxide (SPIO) particles are dependent on the size and
      morphology of tissue blood vessels. In this study, MRI was used to investigate
      changes in the tumor vasculature in an orthotopic primary human pancreatic cancer
      xenograft model during tumor progression. The SPIO contrast agent Feridex I.V.
      was first validated as an intravascular contrast agent over the course of the
      imaging session, and shown to remain in the blood for at least 1.5 h. The average
      vessel size index was not correlated to the tumor area within an image slice, but
      the average blood volume fraction was significantly and negatively correlated to
      the tumor area (p<0.05). Blood volume fraction may serve as a non-invasive
      biomarker for changes in the tumor vasculature due to tumor growth Further
      investigation is needed to evaluate this promising technique as a tool to monitor
      tumor vascular changes in response to antiangiogenic therapies in pancreatic
      cancer.

PMID- 19162791
TI  - Detection of brachytherapy seeds using 3D ultrasound.
AB  - Imaging and detection of brachytherapy seeds using transrectal ultrasound (TRUS)
      remains a challenge for prostate brachytherapy, mainly due to the small size of
      brachytherapy seeds in relatively low-quality B-mode TRUS images. In this paper,
      we propose a new solution for brachytherapy seed detection using 3D ultrasound.
      We use 3D reflected power images computed from ultrasound radio-frequency
      signals, instead of using conventional B-mode images. Then implanted seeds are
      detected in 3D local search spaces that are determined by a priori knowledge.
      Experimental results showed that the proposed solution works well for seed
      localization in the prostate phantom.

PMID- 19162792
TI  - CT and image processing non-invasive indicators of sickle cell secondary
      pulmonary hypertension.
AB  - This retrospective study investigates the potential of image analysis to quantify
      for the presence and extent of pulmonary hypertension secondary to sickle cell
      disease (SCD). A combination of fast marching and geodesic active contours level
      sets were employed to segment the pulmonary artery from smoothed CT-Angiography
      images from 16 SCD patients and 16 matching controls. An algorithm based on fast
      marching methods was used to compute the centerline of the segmented arteries to
      measure automatically the diameters of the pulmonary trunk and first branches of
      the pulmonary arteries. Results show that the pulmonary trunk and arterial
      branches are significantly larger in diameter in SCD patients as compared to
      controls (p-values of 0.002 for trunk and 0.0003 for branches). For validation,
      the results were compared with manually measured values and did not demonstrate
      significant difference (mean p-values 0.71). CT with image processing shows great
      potential as a surrogate indicator of pulmonary hemodynamics or response to
      therapy, which could be an important tool for drug discovery and noninvasive
      clinical surveillance.

PMID- 19162793
TI  - Shape-guided active contour based segmentation and tracking of lumbar vertebrae
      in video fluoroscopy using complex wavelets.
AB  - This paper presents a novel shape-guided active contour based approach for
      segmenting and tracking lumbar vertebrae in video fluoroscopy using complex
      valued wavelets. representations. Due to low radiation exposure levels,
      fluoroscopic images are characterized by low signal-to-noise ratios, low contrast
      resolution, and illumination non-homogeneities both spatially and temporally,
      making current methods ill-suited for segmenting and tracking lumbar vertebrae
      based on existing energy functionals. Furthermore, current methods perform poorly
      in situations characterized by high curvature as found in the structure of lumbar
      spine vertebrae. In this paper, a novel iterative estimation approach is used to
      determine an external energy functional based on complex wavelets. A shaped
      guided algorithm is used to evolve the contour around a lumbar spine vertebra
      based on the complex wavelet energy. The high curvature exhibited by the lumbar
      spine vertebra is addressed through a novel importance sampling scheme.
      Experimental results show that the proposed algorithm achieves significantly
      better segmentation and tracking performance for lumbar spine vertebrae in
      fluoroscopic images when compared to existing techniques.

PMID- 19162794
TI  - Automated segmentation of the quadratus lumborum muscle from magnetic resonance
      images using a hybrid atlas based - geodesic active contour scheme.
AB  - This study presents a novel method for the automatic segmentation of the
      quadratus lumborum (QL) muscle from axial magnetic resonance (MR) images using a
      hybrid scheme incorporating the use of non-rigid registration with probabilistic
      atlases (PAs) and geodesic active contours (GACs). The scheme was evaluated on an
      MR database of 7mm axial images of the lumbar spine from 20 subjects (fast
      bowlers and athletic controls). This scheme involved several steps, including (i)
      image pre-processing, (ii) generation of PAs for the QL, psoas (PS) and erector
      spinae+multifidus (ES+MT) muscles and (iii) segmentation, using 3D GACs
      initialized and constrained by the propagation of the PAs using non-rigid
      registration. Pre-processing of the images involved bias field correction based
      on local entropy minimization with a bicubic spline model and a reverse diffusion
      interpolation algorithm to increase the slice resolution to 0.98 x 0.98 x 1.75mm.
      The processed images were then registered (affine and non-rigid) and used to
      generate an average atlas. The PAs for the QL, PS and ES+MT were then generated
      by propagation of manual segmentations. These atlases were further analysed with
      specialised filtering to constrain the QL segmentation from adjacent non-muscle
      tissues (kidney, fat). This information was then used in 3D GACs to obtain the
      final segmentation of the QL. The automatic segmentation results were compared
      with the manual segmentations using the Dice similarity metric (DSC), with a
      median DSC for the right and left QL muscles of 0.78 (mean = 0.77, sd=0.07) and
      0.75 (mean =0.74, sd=0.07), respectively.

PMID- 19162795
TI  - Determination of food portion size by image processing.
AB  - Overweight and obesity have become an epidemic in many parts of the world
      threatening the health of over one billion people. In order to combat this
      epidemic effectively, it is desirable to develop new methods to monitor
      individual's food intake and provide quantitative information about the nutrients
      and calories consumed in people's daily life. We present an electronic
      photographic approach and associated image processing algorithms to estimate food
      portion size, which is then utilized to obtain the required information. Our
      experiments show that our approach is accurate, providing an effective tool for
      people to track their nutritional and energy intake.

PMID- 19162796
TI  - A classification-based segmentation of cDNA microarray images using Support
      Vector Machines.
AB  - Microarray technology provides a tool for the simultaneous analysis of the
      expression level for an amount of genes. Microarray studies have been shown that
      image processing techniques can significantly influence microarray data
      precision. In this paper we propose a supervised method for the segmentation of
      microarray images based on classification techniques. Support Vector machine is
      employed to classify each pixel of the image into signal, background or
      artefacts. In addition, a preprocessing step is applied in order to filter the
      initial image. The proposed method is applied both to real and simulated images.
      The pixels of the image are classified in two classes for the real images and
      three classes for the simulated one. For this task, an informative set of
      features is used from both green and red channels. The results obtained indicate
      high accuracy (approximately 99%).

PMID- 19162797
TI  - A multisegmental foot model with bone-based referencing: sensitivity to
      radiographic input parameters.
AB  - We present a new kinematic model measuring the three-dimensional orientation of
      multiple segments of the foot and ankle. The model defines neutral alignments
      based on the alignments of the underlying bony segments, and indexes the
      orientation of skin-mounted markers to the bony anatomy using measures from
      weightbearing x-rays. The sensitivity of the model to these radiographic input
      parameters was analyzed using data from walking trials. Kinematic output in each
      plane was found to be most sensitive to perturbations of radiographic
      measurements in that same plane; however, perturbations in the coronal and
      transverse planes demonstrated significant carry-over into other planes. The
      analysis highlights the importance of accurately accounting for the underlying
      anatomy in measuring intersegmental kinematics.

PMID- 19162798
TI  - Effect of vertebral morphology on lumbar kinematics in elderly subjects with
      decreased bone mineral density.
AB  - Correlation between kinematics and morphological characteristics of lumbar spine
      was studied in subjects with varying bone mineral density. Effect of
      morphological characteristics and bone mineral density on the lumbar spine
      movement was investigated. Morphology parameters were measured from radiographs
      and a high-frequency motion tracking device were employed to detect surface
      movement of lumbar spine. Multiple regression analysis identified factors
      influencing lumbar kinematics while ANOVA examined differences in morphology with
      normal bone mineral density, osteopenia and osteoporosis. The results show that
      morphological characteristics, such as wedging deformity, are indeed influential
      to the kinematics. Related to our previous report, abnormal lumbar kinematic
      pattern in the subjects with osteoporosis, this study shows although
      morphological characteristics were found significantly different among normal,
      osteopenia, and osteoporosis subjects, the change in lumbar kinematic pattern
      could not be fully explained by the altered vertebral or disc morphology.

PMID- 19162799
TI  - Modeling the relation between muscle thickness and wrist angle based on bone
      muscle lever model.
AB  - Muscle modeling is a powerful tool to study the skeletal muscle, and can give a
      better perception of the mechanisms of muscular functions. In this study, a
      mathematical model was proposed based on the bone-muscle lever model to
      illuminate the non-linear relation between the thickness of extensor carpi
      radialis muscle and wrist angle. The ultrasound image, SEMG signals were
      synchronously sampled from the extensor carpi radialis muscle together with the
      wrist angle during the whole process of wrist extension and flexion to validate
      the model. The wrist angle was then calculated using the measured muscle
      thickness by this model. The overall mean correlation coefficient value was 0.96
      +/- 0.02, and the overall mean standard root mean square error was 5.82 +/- 1.95,
      which were much better than the results of other regression methods. The results
      show that the wrist angle is well predicted by our model, and it suggests that
      this model is helpful to study the relationship between internal muscle
      structural changes and external limb behaviors.

PMID- 19162800
TI  - A subject-specific finite element model of the anterior cruciate ligament.
AB  - The anterior cruciate ligament (ACL) is commonly injured. The stress distribution
      in the ACL is the key for understanding its function and injury mechanism, as
      well as for developing optimal surgical reconstruction protocols. In this study,
      a three-dimensional subject-specific finite element model of human ACL was
      developed. Bony geometries were reconstructed from CT scan images, while the
      geometry of the ACL and the orientation of its fiber bundles were measured via a
      mechanical digitizer. A transversely isotropic, hyperelastic, and nearly
      incompressible constitutive model was implemented to describe the mechanical
      properties of the ACL. A 134N anterior tibial load were applied to a cadaveric
      knee specimen at full extension, 30 degrees , and 60 degrees of flexion by a 6
      DOF Robotic/Universal Force-moment Sensor (UFS) system, which was also used to
      measure the ACL resultant force. Knee kinematics was collected by digitizing two
      registration blocks attached to the femur and the tibia, respectively, and was
      input into the FE model as boundary conditions. The resultant force of the ACL
      calculated by the FE model was comparable to the experimental data, with the
      error within 10%, thus validated the model. The FE results showed that the
      average stress in the ACL was between the range 4.7-5.0MPa, with a peak stress
      between the range 9.8-10.9MPa, which shifted from the posterior lateral (PL)
      bundle to the anterior medial (AM) bundle as the knee flexed.

PMID- 19162801
TI  - Computer simulation of knee arthrometry to study the effects of partial ACL
      injury and tibiofemoral contact.
AB  - We simulated the knee arthrometry test to obtain a deeper understanding of the
      joint's stability behavior and interpret the arthrometric results more
      effectively. A 2D sagittal plane finite element model of the lower limb in the
      standard configuration of knee arthrometry was developed using ANSYS APDL. A
      detailed model of the knee joint was considered including the femoral
      articulating contour represented by an ellipse, the tibial plateau represented by
      a circular arc, and four major knee ligaments and their individual bundles
      represented by linear and nonlinear tensile springs. A deformable layer of
      articular cartilage was also considered over the tibial plateau to simulate the
      bones engagement more precisely. The model was analyzed while the tibia was
      subjected to an anterior drawer force of up to 150 N with 10 N increments and the
      tibial anterior translation was obtained. Simulation of the arthrometry test for
      different curvatures of the tibial plateau revealed that the bones engagement has
      a considerable effect on the knee joint's laxity. However, a considerable change
      from the intact knee's data curve was only observed when the ACL total ruptured
      was simulated. This emphasizes the difficult task involved when trying to
      distinguish the partial injuries of the ACL using arthrometric data.

PMID- 19162802
TI  - The effects of geometry and fiber bundle orientation on the finite element
      modeling of the anterior cruciate ligament.
AB  - The anterior cruciate ligament (ACL) has irregular geometry and spirally oriented
      fiber bundle organization, which are closely related to its physiological
      function. In previous finite element (FE) models, however, these two features are
      neglected due to the difficulty of obtaining its complex geometry and spiral
      fiber bundle orientation. Based on a previously developed and validated FE model,
      this study performed parametric studies to evaluate the effects of geometry and
      fiber bundle orientation on the FE modeling of the ACL. To evaluate the effect of
      the geometry, two models were compared: 1) with realistic ACL geometry obtained
      by using digitizer; 2) with ACL geometry reconstructed by directly connecting the
      femur and tibia insertion sites as commonly used in previous studies. To evaluate
      the effect of fiber bundle orientation, another two models were compared: 1) with
      realistic fiber bundle orientation obtained by using digitizer (alpha=38 degrees
      ); 2) with unrealistic fiber bundle orientation (alpha=0 degrees ). The same
      kinematics obtained by a Robotic/Universal Force-moment Sensor (UFS) system was
      input into the models as boundary conditions. The resultant forces calculated by
      the models were compared to the experimental data. The model with unrealistic
      geometry had a 40% higher ACL resultant force compared to the experimental data,
      while the model with the realistic ACL geometry well predicted the ACL resultant
      force, with an error less than 10%. When evaluating the effect of fiber bundle
      orientation, the model with unrealistic fiber bundle orientation predicted
      similar ACL resultant forces and stress distribution as the model with realistic
      fiber bundle orientation. The results revealed that ACL geometry has a
      significant effect on the FE model while fiber orientation does not.

PMID- 19162803
TI  - Seizure detection in neonates: Improved classification through supervised
      adaptation.
AB  - The goal of neonatal seizure detection is the development of a patient
      independent system to alert staff in the neonatal intensive care unit of ongoing
      seizures. This study demonstrates the potential in adapting a patient independent
      classifier using patient specific data. Supervised adaptation is investigated
      using the basic gradient descent algorithm and least mean squares procedures. An
      increase in mean ROC area of 3% is obtained for the best performing learning
      algorithm, yielding an increase in mean accuracy of 7.7% compared to the patient
      independent algorithm.

PMID- 19162804
TI  - Detection of neonatal EEG seizure using multichannel matching pursuit.
AB  - It is unusual for a newborn to have the classic "tonic-clonic" seizure
      experienced by adults and older children. Signs of seizure in newborns are either
      subtle or may become clinically silent. Therefore, the electroencephalogram (EEG)
      is becoming the most reliable tool for detecting neonatal seizure. Being non
      stationary and multicomponent, EEG signals are suitably analyzed using time
      frequency (TF) based methods. In this paper, we present a seizure detection
      method using a new measure based on the matching pursuit (MP) decomposition of
      EEG data. Signals are represented in the TF domain where seizure structural
      characteristics are extracted to form a new coherent TF dictionary to be used in
      the MP decomposition. A new approach to set data-dependent thresholds, used in
      the seizure detection process, is proposed. To enhance the performance of the
      detector, the concept of areas of incidence is utilized to determine the
      geometrical correlation between EEG recording channels.

PMID- 19162805
TI  - A novel dual-stage classifier for automatic detection of epileptic seizures.
AB  - In long-term monitoring of electroencephalogram (EEG) for epilepsy, it is crucial
      for the seizure detection systems to have high sensitivity and low false
      detections to reduce uninteresting and redundant data that may be stored for
      review by the medical experts. However, a large number of features and the
      complex decision boundaries for classification of seizures eventually lead to a
      trade-off between sensitivity and false detection rate (FDR). Thus, no single
      classifier can fulfill the requirements of high sensitivity with a low FDR and at
      the same time be a computationally efficient system suitable for real-time
      application. We present a novel, simple, computationally efficient seizure
      detection system to enhance the sensitivity with a low FDR by proposing a dual
      stage classifier. This overall system consists of a pre-processing unit, a
      feature extraction unit and a novel dual-stage classifier. The first stage of the
      proposed classifier detects all true seizures, but also many false patterns,
      whereas the second stage of the proposed classifier minimizes false detections by
      rejecting patterns that may be artifacts. The performance of the novel seizure
      detection system has been evaluated on 300 hours of single-channel depth
      electroencephalogram (SEEG) recordings obtained from fifteen patients. An overall
      improvement has been observed in terms of sensitivity, specificity and FDR.

PMID- 19162806
TI  - Automated single channel seizure detection in the neonate.
AB  - Neonatal seizures are the most common neurological emergency in the neonatal
      period and are associated with poor long-term outcome. EEG is considered the gold
      standard for identification of all neonatal seizures, reducing the number of EEG
      electrodes required would reduce patient handling and allow faster acquisition of
      data. A method for automated neonatal seizure detection based on two carefully
      chosen cerebral scalp electrodes but trained using multi-channel EEG is
      presented. The algorithm was developed and tested using a multi-channel EEG
      dataset containing 411 seizures from 251.9 hours of EEG recorded from 17 full
      term neonates. Automated seizure detection using a variety of bipolar channel
      derivations was investigated. Channel C3-C4 yielded correct detection of 90.77%
      of seizures with a false detection rate of 9.43%. This compares favourably with a
      multi-channel seizure detection method which detected 81.03% of seizures with a
      false detection rate of 3.82%.

PMID- 19162807
TI  - A novel wavelet-based index to detect epileptic seizures using scalp EEG signals.
AB  - In this paper, we propose a novel wavelet-based algorithm for the detection of
      epileptic seizures. The algorithm is based on the recognition of rhythmic
      activities associated with ictal states in surface EEG recordings. Using a moving
      window analysis, we first decomposed each EEG segment into a wavelet packet tree.
      Then, we extracted the coefficients corresponding to the frequency band of
      interest defined for rhythmic activities. Finally, a normalized index sensitive
      to both the rhythmicity and energy of the EEG signal was derived, based on the
      resulting coefficients. In our study, we evaluated this combined index for real
      time detection of epileptic seizures using a dataset of approximately 11.5 hours
      of multichannel scalp EEG recordings from three patients and compared it to our
      previously proposed wavelet-based index. In this dataset, the novel combined
      index detected all epileptic seizures with a false detection rate of 0.52/hr.

PMID- 19162808
TI  - Quadratic time-frequency distribution selection for seizure detection in the
      newborn.
AB  - Several, recently proposed, newborn EEG seizure detection techniques use
      quadratic time-frequency distributions (QTFDs) to generate the time-frequency
      representations (TFRs) at their core. The specific type of QTFD that provides the
      best discrimination between the TFR of nonseizure and seizure epochs of EEG,
      however, has yet to be thoroughly investigated. This paper proposes the selection
      of an optimal QTFD that maximises the the absolute error between seizure and
      nonseizure QTFDs calculated on a database of newborn EEG. The optimisation
      procedure is a data driven process that selects the optimal QTFD based on the
      distribution of the absolute error between nonseizure/nonseizure QTFDs and the
      seizure/nonseizure QTFDs. Several non-adaptive QTFDs were selected for comparison
      and those selected were subjected to a restriction on the kernel's volume to
      ensure that the QTFD can accurately represent the time-frequency distribution of
      signal energy. The results show that a lag independent or narrowband QTFD such as
      the modified B distribution provides a QTFD that best highlights the difference
      in time-frequency signal energy between newborn EEG seizure and nonseizure.

PMID- 19162809
TI  - Epileptic seizure detection in EEG recordings using phase congruency.
AB  - This paper presents the use of phase congruency to robustly detect the epileptic
      seizure. Phase congruency is calculated from log Gabor wavelets. Numbers of
      spikes detected from the phase congruency of two classes of EEG data (epilepsy
      and seizure free) are used as the features of interest. By using only one
      dimensional features, the detection accuracies of the proposed method are
      comparable with the existing magnitude-based methods.

PMID- 19162810
TI  - Autonomic nervous system response to vibrating and electrical stimuli on the
      forearm and wrist.
AB  - In today's operating rooms, anesthesiologists use physiological data monitoring
      systems with visual and auditory cues to receive patient information. The
      efficacy of these visual-audio systems is limited by the human limitations of
      these modalities. Previous studies have shown the potential use of a
      complementary, or alternate, patient data monitoring technology utilizing another
      psychophysically relevant modality: the sense of touch via vibro-tactile or
      electro-tactile stimulation. In this paper, we describe an experiment designed to
      determine whether the specific type and/or location of such a tactile stimulation
      device on the arm affects the autonomic nervous system response. In our study,
      each of 10 participants tested a vibro-tactile display on the forearm (VF), a
      vibro-tactile display on the wrist (VW), and an electro-tactile display on the
      forearm (EF) in random order. Using the LifeShirt, system, electrocardiogram
      (ECG), respiratory rate (Br), tidal volume (Vt) data were collected. Results
      showed a higher value of the heart rate and heart rate variability (HRV) when
      using the VF compared to the VW and EF. We also found that the HRV response for
      the three tactile prototypes was correlated with the accuracy of tactile pattern
      identification.

PMID- 19162811
TI  - Embedded capacitive sensor system for hip surgery rehabilitation: online
      measurements and long-term stability.
AB  - We are developing an embedded system that measures the force between foot and
      insole with a low-cost laminated capacitive sensor matrix. The system is intended
      to guide a hip surgery patient to train the operated leg with a suitable force.
      In this paper, we present an embedded measurement system, which is able to
      estimate the total plantar force in real-time and to give instant feedback to a
      user. We also present a method for compensating the drift of capacitive sensors.
      A 5-hour long test measurement was made in order to validate the system.
      According to the preliminary test, the compensation method effectively prevents
      the drift of the baseline of the force reading.

PMID- 19162812
TI  - Real-time observation of potential conformational changes of proteins during
      electromagnetic field exposure.
AB  - A novel experimental setup for the exposure of proteins to uniform
      electromagnetic fields in the frequency range from 50MHz up to 2GHz is presented.
      The exposure chamber can be placed in the measurement compartment of an existing
      spectropolarimeter recording the circular dichroism signal. Therefore, potential
      conformational changes induced by the electromagnetic fields can be observed.
      Since the point of observation becomes identical with the potential
      electromagnetic field interaction site in space and time, the detection of even
      small effects becomes possible. Furthermore, by examining temperature sensitive
      proteins like GrpE, thermal and non-thermal effects of electromagnetic fields
      should be distinguishable due to the different time scale of immediate and
      thermally induced effects.

PMID- 19162813
TI  - Parallel multipoint recording of aligned and cultured neurons on corresponding
      Micro Channel Array toward on-chip cell analysis.
AB  - This paper describes an advanced Micro Channel Array (MCA) so as to record
      neuronal network at multiple points simultaneously. Developed MCA is designed for
      neuronal network analysis which has been studied by co-authors using MEA (Micro
      Electrode Arrays) system. The MCA employs the principle of the extracellular
      recording. Presented MCA has the following advantages. First of all, the
      electrodes integrated around individual micro channels are electrically isolated
      for parallel multipoint recording. Sucking and clamping of cells through micro
      channels is expected to improve the cellular selectivity and S/N ratio. In this
      study, hippocampal neurons were cultured on the developed MCA. As a result, the
      spontaneous and evoked spike potential could be recorded by sucking and clamping
      the cells at multiple points. Herein, we describe the successful experimental
      results together with the design and fabrication of the advanced MCA toward on
      chip analysis of neuronal network.

PMID- 19162814
TI  - Functional evaluation of magnetic microactuators for removing biological
      accumulation: an in vitro study.
AB  - Here we demonstrate the functional capability of microfabricated magnetic
      actuators in clearing biological accumulation on a model catheter pore. Cell
      clearing performance was quantitatively measured by comparing the effect of
      actuation on the cell density of aggressively growing adherent murine cells.
      Devices were actuated at a frequency of 100 Hz and a magnetic field of 17.8 kA/m
      for 30, 45, or 60 min. On average, microactuators removed 37.4% of the adherent
      cells. The results also revealed that the cell-clearing capability of the
      microactuator increased as a function of the actuation duration and angle of
      deflection.

PMID- 19162815
TI  - Numerical analysis of temperature elevation in the head due to power dissipation
      in a cortical implant.
AB  - This article presents the numerical analysis of temperature increase in the human
      head resulting from the power dissipation in a cortical implant. A 3-D head
      phantom with 22 tissue types and 0.2 mm x 0.2 mm x 2 mm resolution has been used
      in the simulations. The dependencies of the temperature increase on the power
      dissipation level, chip size, and location of the implant are investigated.
      Moreover, distributing power dissipation by using multiple integrated circuits in
      the implant is discussed. Maximum allowable total power dissipation in a cortical
      implant of size 2 x 2 mm2 is found to be 4.8 mW, whereas, it is 8.4 mW for an
      implant with two chips of same size placed 10 mm apart.

PMID- 19162816
TI  - An approximation model of myocardial crossbridge for weak coupling calculation of
      left ventricle model and circulation model.
AB  - It is necessary to use complicated myocardial cell model and heart model to
      evaluate the regional energy production and consumption which leads to the
      unrealistic computational time. In this research, a left ventricle (LV)
      simulation model was constructed which includes accurate myocardial cell model.
      In order to simulate the model in realistic time, we introduced an approximation
      model of the crossbridge model which can be calculated with weak coupling
      calculation. The LV model was combined with a circulation model to validate the
      proposed model by calculating the hemodynamics parameters and ventricular
      energetics indices. The ESPVR (End Systolic Pressure Volume Relation) showed
      linear relation, and also the PVA - ATP consumption relation showed linear
      relation which are widely known as the physiological characteristics of mammalian
      hearts. From these results, we can say that the model can be used as a model for
      physiological simulation experiments which are related to the ventricular
      energetics.

PMID- 19162817
TI  - On the calculation of principle curvatures of the left-ventricular surfaces.
AB  - A local description of the shape of the left ventricle is relevant in assessing
      the process of adverse ventricular remodeling, associated with most cardiac
      pathologies, and in monitoring reverse remodeling by therapy. To quantify local
      shape of the left ventricle, one can calculate the curvature of its epicardial or
      endocardial surface. The 3D geometry of the heart and especially the ventricles,
      can typically be described using finite element meshes. From a mathematical point
      of view these meshes provide a local parametrization of the surface in the 3
      dimensional space. We discuss the analytic derivation of the principle curvatures
      of the left-ventricular surfaces given their smooth finite-element meshes and
      apply this derivation to assess the regional shape of the normal porcine left
      ventricle.

PMID- 19162818
TI  - In-vitro evaluation of sensors and amplifiers to measure left ventricular
      pressure in mice.
AB  - Mice are becoming more common as research models, and several companies now
      manufacture sensors and instrumentation to measure left ventricular (LV) pressure
      and volume in mice. It is often assumed that pressure is easier to measure than
      volume, and that all sensors perform similarly, but there are differences. We
      measured in-vitro the frequency and step responses, immersion response,
      stability, accuracy, linearity, and sensitivity to lateral or bending force of
      several solid-state sensors and amplifiers commonly used in mice. We tested 4
      microsensors each from Millar, Scisense, and RADI, and also fluid-filled
      catheters. All solid-state sensors were stable with drifts of 1 mmHg/hr, had flat
      frequency response to >1 kHz, and were accurate and linear to within +/- 2 mmHg
      from 0-300 mmHg. The frequency response of the fluid-filled catheter was down by
      50% at 30 Hz. The amplifiers from Millar, Scisense, and RADI, had time delays of
      0.2, 3.2 and 10.6 ms respectively. The Millar and RADI sensors were unresponsive
      to lateral forces, but the Scisense catheters had sensitivities as high as 5.3
      mmHg/g. There are significant differences in solid state pressure sensors and
      amplifiers which could generate offsets, time delays, and distortions which could
      go unrecognized in-vivo.

PMID- 19162819
TI  - High resolution contrast ultrasound and NADH fluorescence imaging of myocardial
      perfusion in excised rat hearts.
AB  - Simultaneous imaging of myocardial flow and hypoxia could be vital for
      identifying acute ischemic mechanisms that may trigger an arrhythmia. We have
      studied the distribution of flow and hypoxia in excised locally ischemic rat
      hearts using simultaneous contrast ultrasound imaging and beta-nicotinamide
      adenine dinucleotide (NADH) fluorescence imaging. Local ischemia was induced by
      controlling flow within a major coronary artery. Intra-myocardial flow was imaged
      using contrast high-resolution ultrasound (linear probe; 13-6 MHz). An ultrasound
      contrast agent (UCA) was used to highlight the ischemic border. We observed
      distinct borders between two perfusion beds. UCA images showed high contrast
      borders of flow. The progression of UCA through the tissue was clearly visible.
      Intramyocardial regions of flow overlap could be identified by superimposing
      images of UCA from two perfusion zones. Borders between hypoxic and normoxic
      tissue were clearly revealed by increased NADH fluorescence. Hypoxic borders were
      oriented along borders of flow. In summary, simultaneous ultrasound and NADH
      imaging of excised hearts from small animals provide high fidelity images for
      characterizing the distribution of flow and hypoxic tissue during acute localized
      ischemia.

PMID- 19162820
TI  - Preliminary study on the estimation of Emax using single-beat methods during
      assistance with rotary blood pumps.
AB  - Recently, rotary blood pumps (RBPs) have been used as bridge to recovery. In such
      application the RBP might be weaned once the cardiac function has been recovered.
      In such cases, the detection of the cardiac function is fundamental for the
      treatment efficiency. However, most of the widely used cardiac function indices
      (CFIs) were proposed for unassisted hearts and have not been completely evaluated
      under assistance. In contrast, Emax, which is known as a reliable CFI, has
      already been validated under assistance with RBP. However, since the conventional
      method for the estimation of Emax has some limitations for the clinical
      application, the objective of this study was to evaluate different single-beat
      estimation methods qualitatively and also quantitatively using in vivo data. The
      preliminary results showed that although single-beat estimation have more
      clinical applicability, not all those estimation methods are suitable for the RBP
      assistance.

PMID- 19162821
TI  - Wireless application in intravenous infiltration detection system.
AB  - The IrDA wireless protocol has been applied to a fiber optics based point-of-care
      system for the detection of intravenous infiltration. The system is used for
      monitoring patients under infusion therapy. It is optimized for portability by
      incorporating a battery source and wireless communication. The IrDA protocol
      provides secure data communication between the electronic module of the system
      and the PDAs carried by the nurses. The PDA is used for initiating the actions of
      the electronic module and for data transfer. Security is provided by specially
      designed software and hardware.

PMID- 19162822
TI  - Wearable microwave radiometers for remote fire detection: System-on-Chip (SoC)
      design and proof of the concept.
AB  - The paper reports the present status of the project aimed at the realization of a
      wearable low-cost low-power System-on-Chip (SoC) 13-GHz passive microwave
      radiometer in CMOS 90 nm technology. This sensor has been thought to be inserted
      into the firemen jacket in order to help them in the detection of a hidden fire
      behind a door or a wall, especially where the IR technology fail. With respect of
      the prior art, the SoC is further developed and a proof of the concept is
      provided by means of a discrete-component prototype.

PMID- 19162823
TI  - Magnetic endotracheal tube imaging device.
AB  - This paper describes an accurate, economical, and portable device that helps to
      locate the position of an endotracheal tube (ETT) in situ. The device uses an
      array of magnetic field sensors to detect an anomaly in magnetic field caused by
      magnet embedded near the cuff of an ETT, and displays an intuitive map of
      relative magnetic field intensity under the sensor area. The device provides real
      time feedback of the position to a clinician, so that corrective measures can be
      taken if the ETT is determined to be outside of normal positioning with respect
      to the patient's airway. Variations of the proposed design are suitable for
      continuous monitoring.

PMID- 19162824
TI  - Motion based adaptive calibration of pulse transit time measurements to arterial
      blood pressure for an autonomous, wearable blood pressure monitor.
AB  - This paper presents a novel adaptive algorithm for calibrating non-invasive pulse
      transit time (PTT) measurements to arterial blood pressure (BP). This new
      algorithm allows complete calibration of PTT to BP without the use of an
      oscillometric blood pressure cuff or external pressure sensor. Further, the
      algorithm can be used to continually update the identified parameters in the
      calibration equation while the patient is wearing the device. The technique
      utilizes natural patient motion to generate a known change in the transmural
      pressure (input) acting on the arteries monitored by our device to produce a
      measurable change in pulse transit time (output). The natural motion includes
      varying the height of the sensor relative to the heart to alter hydrostatic
      pressure at the measurement site and adjusting proximal joint posture to vary the
      external arterial pressure at the measurement site. This new algorithm is applied
      to a unique wearable sensor architecture that combines two in-line PPG sensors,
      one located at the ulnar artery of the wrist and one located at the digital
      artery of the little finger along with a multi-axis accelerometer for height
      measurement. Initial human subject tests results using the new algorithm and
      device will be presented.

PMID- 19162825
TI  - Design of a wireless telemetric backpack device for real-time in vivo measurement
      of pressure-volume loops in conscious ambulatory rats.
AB  - Pressure - Volume (PV) analysis is the de facto standard for assessing myocardial
      function. Conductance based methods have been used for the past 27 years to
      generate instantaneous left ventricular (LV) volume signal. Our research group
      has developed the instrumentation and the algorithm for obtaining PV loops based
      on the measurement of real - time admittance magnitude and phase from the LV of
      anaesthetized mice and rats. In this study, the instrumentation will be
      integrated into an ASIC (Application Specific Integrated Circuit) and a backpack
      device will be designed along with this ASIC. This will enable measurement of
      real-time in vivo P-V loops from conscious and ambulatory rats, useful for both
      acute and chronic studies.

PMID- 19162826
TI  - Voice quality monitoring: a portable device prototype.
AB  - This paper addresses the important issue of voice monitoring throughout the day
      under a clinical perspective. This problem is of great concern, for
      rehabilitation and from the assistive technology point of view. A prototype for a
      new portable device is proposed, implementing basic voice quality indexes
      (fundamental frequency F0, jitter, relative average perturbation RAP, noise) by
      means of robust high-resolution techniques. The device is contact-less, as the
      transducer is a small microphone included in the device. A feedback for patients
      outside the clinic is provided, given by a led/audio unit that advices the
      patient for any abnormal vocal emission, to help patients with carryover of
      therapy goals outside the clinical environment. The device will collect audio
      recordings to be submitted to a PC for further analysis, to be performed off
      line. Such device for self-diagnosis and vocal rehabilitation could give a valid
      support, both to clinicians and patients.

PMID- 19162827
TI  - Classification of EEG with structural feature dictionaries in a brain computer
      interface.
AB  - We present a new method for the classification of EEG in a brain computer
      interface by adapting subject specific features in spectral, temporal and spatial
      domain. For this particular purpose we extend our previous work on ECoG
      classification based on structural feature dictionary and apply it to extract the
      spectro-temporal patterns of multichannel EEG recordings related to a motor
      imagery task. The construction of the feature dictionary based on undecimated
      wavelet packet transform is extended to block FFT. We evaluate several subset
      selection algorithms to select a small number of features for final
      classification. We tested our proposed approach on five subjects of BCI
      Competition 2005 dataset- IVa. By adapting the wavelet filter for each subject,
      the algorithm achieved an average classification accuracy of 91.4% The
      classification results and characteristic of selected features indicate that the
      proposed algorithm can jointly adapt to EEG patterns in spectro-spatio-temporal
      domain and provide classification accuracies as good as existing methods used in
      the literature.

PMID- 19162828
TI  - Multiclass voluntary facial expression classification based on Filter Bank Common
      Spatial Pattern.
AB  - This paper investigates the classification of voluntary facial expressions from
      electroencephalogram (EEG) and electromyogram (EMG) signals using the Filter Bank
      Common Spatial Pattern (FBCSP) algorithm. The FBCSP algorithm is an autonomous
      and effective machine learning approach for classifying two classes of EEG
      measurements in motor imagery-based Brain Computer Interface (BCI). However, the
      problem of facial expression recognition typically involves more than just two
      classes of measurements. Hence, this paper proposes an extension of FBCSP to the
      multiclass paradigm using a decision threshold-based classifier for classifying
      facial expressions from EEG and EMG measurements. A study is conducted using the
      proposed Multiclass FBCSP on 4 subjects who performed 6 different facial
      expressions. The results show that the Multiclass FBCSP is effective in
      classifying multiple facial expressions from the EEG and EMG measurements.

PMID- 19162829
TI  - An on-line BCI for control of hand grasp sequence and holding using adaptive
      probabilistic neural network.
AB  - This paper presents a new EEG-based Brain-Computer Interface (BCI) for on-line
      controlling the sequence of hand grasping and holding in a virtual reality
      environment. The goal of this research is to develop an interaction technique
      that will allow the BCI to be effective in real-world scenarios for hand grasp
      control. Moreover, for consistency of man-machine interface, it is desirable the
      intended movement to be what the subject imagines. For this purpose, we developed
      an on-line BCI which was based on the classification of EEG associated with
      imagination of the movement of hand grasping and resting state. A classifier
      based on probabilistic neural network (PNN) was introduced for classifying the
      EEG. The PNN is a feedforward neural network that realizes the Bayes decision
      discriminant function by estimating probability density function using mixtures
      of Gaussian kernels. Two types of classification schemes were considered here for
      on-line hand control: adaptive and static. In contrast to static classification,
      the adaptive classifier was continuously updated on-line during recording. The
      experimental evaluation on six subjects on different days demonstrated that by
      using the static scheme, a classification accuracy as high as the rate obtained
      by the adaptive scheme can be achieved. At the best case, an average
      classification accuracy of 93.0% and 85.8% was obtained using adaptive and static
      scheme, respectively. The results obtained from more than 1500 trials on six
      subjects showed that interactive virtual reality environment can be used as an
      effective tool for subject training in BCI.

PMID- 19162830
TI  - Optimal input selection for neural machine interfaces predicting multiple non
      explicit outputs.
AB  - This study implemented a novel algorithm that optimally selects inputs for neural
      machine interface (NMI) devices intended to control multiple outputs and
      evaluated its performance on systems lacking explicit output. NMIs often
      incorporate signals from multiple physiological sources and provide predictions
      for multidimensional control, leading to multiple-input multiple-output systems.
      Further, NMIs often are used with subjects who have motor disabilities and thus
      lack explicit motor outputs. Our algorithm was tested on simulated multiple-input
      multiple-output systems and on electromyogram and kinematic data collected from
      healthy subjects performing arm reaches. Effects of output noise in simulated
      systems indicated that the algorithm could be useful for systems with poor
      estimates of the output states, as is true for systems lacking explicit motor
      output. To test efficacy on physiological data, selection was performed using
      inputs from one subject and outputs from a different subject. Selection was
      effective for these cases, again indicating that this algorithm will be useful
      for predictions where there is no motor output, as often is the case for disabled
      subjects. Further, prediction results generalized for different movement types
      not used for estimation. These results demonstrate the efficacy of this algorithm
      for the development of neural machine interfaces.

PMID- 19162831
TI  - The estimation of long-term memory characteristics in MEA neuronal culture
      recordings.
AB  - The nonlinear analysis of multichannel MEA recordings from neuronal networks is
      becoming a central topic in Neuroengineering. Up-to-date these kind of analyses
      required complex ad hoc methods. In this paper we introduce a new approach that
      allows the analysis of the whole-neuronal-network-activity with well-established
      nonlinear signal processing methods. In particular, we show here the estimation
      of long-term-memory behaviors through the Periodogram method in the bursting
      activity of cortical neuron cultures during development. Moreover, we show how
      this method is able to highlight structural activity changes of the network.

PMID- 19162832
TI  - Task-irrelevant alpha component analysis in motor imagery based brain computer
      interface.
AB  - In motor imagery based BCI, the alpha rhythm shares the same frequency band with
      sensorimotor rhythm (SMR), and does not correlate with mental task, which
      contaminates the SMR recording. Independent component analysis (ICA) was applied
      to decompose original EEG signal into source components, and a comprehensive
      method was proposed to discriminate those source components by combining
      temporal, frequency, spatial, and class label information. Task-irrelevant alpha
      components were sorted out and their projections were reduced by proper bipolar
      electrode placement for improving the BCI performance.

PMID- 19162833
TI  - Evaluations of tactile displays of physiological monitoring.
AB  - Physiological monitoring devices are used in the operating room (OR) to identify
      abnormal changes. They are currently detected by the anesthesiologist from direct
      observation of visual displays or by auditory cues. In an effort to improve OR
      safety, we explored the use of an alternative sensory modality, touch, to
      effectively and accurately convey patients' physiological information. To be
      accepted [1] such devices need to fulfill five criteria: learnability, errors,
      efficiency, memorability and satisfaction. We designed and compared various
      tactile displays in respect to some of these criteria.

PMID- 19162834
TI  - Can technology further improve the safety of anesthesia?
AB  - Improvements in monitoring technology have made it possible to collect extensive
      amounts of physiological data from patients. This volume of data has enormous
      potential to assist in diagnosis and treatment, but is relatively untapped due to
      unintelligent monitors and limited human attention. To improve patient care and
      prevent adverse outcomes, we need to integrate the averaged variables, trend
      information and expert knowledge. Continued improvements to patient safety are
      hampered by three key factors: unintelligent alarm systems, excessive data, and
      human cognitive limitations. A concerted effort is required, using a multifaceted
      approach, to harness the potential of the vast amount of information produced at
      the clinical interface.

PMID- 19162835
TI  - The use of mathematical models and clinical knowledge in intraoperative vital
      sign trend monitoring.

PMID- 19162836
TI  - Graphic data displays to detect-diagnose-treat critical events during anesthesia.

PMID- 19162837
TI  - Perceptual limits on the visual monitoring task.
AB  - A brief review is presented of recent work in vision science showing important
      limits on the ability of observers to carry out various tasks. First, it has been
      found that only a few moving items can be tracked at any time, even after
      considerable practice. Second, observers can often miss the appearance of
      unexpected objects or events, even if these are large. Third, observers can often
      miss changes that occur in front of them, even when these changes are large,
      repeated, and expected. Finally, observers simply cannot see two changes at a
      time, no matter how hard they try. The explanation for these effects is briefly
      discussed, along with the reasons why these limits are not usually noticed. Some
      suggestions are also given about what (if anything) can be done to mitigate their
      effects in regards to the visual monitoring task of the anesthesiologist.

PMID- 19162838
TI  - Study on time-frequency characteristics of cellular transmenbrane potentials
      based on equivalent circuit model.
AB  - An equivalent circuit model of spherical biological cell subjected to pulsed
      electric field (PEF) is introduced, on the basis of multilayer dielectric model
      and complex-domain analysis. The transfer functions of inner and outer membranes
      are also presented. By introducing the time-domain solutions of transmembrane
      potentials induced by PEF, the relationship between electric field parameters and
      transmembrane potentials is discussed. It is found that different duration can
      result in different selective effect on inner and outer membranes. Frequency
      domain analysis shows that inner and outer membranes exhibit band-pass and low
      pass filter characteristic in response to PEF, respectively. Both the time-domain
      and frequency-domain analyses show that the circuit model agrees well with the
      dielectric model and can give preliminary explanation for bioelectric effects
      induced by PEF, such as electroporation and intracellular electromanipulation.
      The circuit model, which is not computationally demanding but useful, provides a
      technique complementing other numerical and analytical methods for application of
      PEF in tumor treatment.

PMID- 19162839
TI  - In silico simulation of epithelial cell tubulogenesis.
AB  - By improving our understanding of epithelial cell tubulogenesis in vitro we
      should improve our understanding of how these cells organize to form normal
      tissues such as the ducts and lobules that make up breast tissue. We do not fully
      understand how these ducts and lobules form. Because it is difficult to directly
      control and observe epithelial cell morphogenesis in vivo, we study it using in
      vitro culture systems. They are more easily controlled and observed. One of the
      most well studied models of tubulogenesis uses Madin-Darby canine kidney (MDCK)
      cells in culture systems: single cell layered cysts form tubules when exposed to
      hepatocyte growth factor (HGF). We have developed an in silico analogue that
      mimics the fundamental cell-level operating principles and system-level
      phenotypes of in vitro MDCK tubulogenesis. The creation and validation of the
      analogue required the specification and questioning of currently held
      assumptions. The analogue can be used to test hypotheses about mechanisms and in
      silico operating principles that may have in vitro counterparts. By increasing
      our understanding of the operating principles that govern in vitro epithelial
      cell growth and organization we are better positioned to understand how best to
      manipulate these operating principles to achieve specific tissue engineering
      objectives.

PMID- 19162840
TI  - Protective antigen composite nanofibers as a transdermal anthrax vaccine.
AB  - Anthrax, a disease caused by the gram positive bacteria Bacillus anthracis, has
      become an increasing threat to public health in the last several years, due to
      its use as an agent of biological warfare. The currently utilized human anthrax
      vaccine, which confers immunity through the host antibody recognition of
      protective antigen (PA), requires a three dose regimen and annual booster shots
      after the initial vaccination to maintain its efficacy. The long term goal of
      this project is to produce an anthrax vaccine that is capable of delivering
      protective antigen through human skin. The novel method for transdermal vaccine
      delivery that we propose utilizes the high surface area to volume ratio offered
      by protein-containing nanofiber membranes, prepared by the electrospinning
      technique. Research has already been undertaken to study the effect the main
      virulent agent of anthrax, lethal toxin (LT), has on a human monocytic cell line,
      Monomac 6 cells (MM6). Lethal toxin is said to comprise of a Zn2+ -dependent
      metalloprotease known as lethal factor (LF), and a binding protein known as
      protective antigen. The successful encapsulation of the protective antigen within
      the nanofibrous membrane was analyzed with the use of an in vitro MM6 assay. The
      assay was designed to ensure the functionality of PA through the harsh
      environment of the electrospinning process. Quantitative analysis of IL-6
      cytokine production by lipopolysaccharide (LPS) stimulated MM6 cells in the
      presence of LF and PA provided proof that PA retained its biological activity
      through the process of electrospinning. This finding provides an innovative
      platform for the development of a transdermal anthrax vaccine.

PMID- 19162841
TI  - Experiment and mechanism research of SKOV3 cancer cell apoptosis induced by
      nanosecond pulsed electric field.
AB  - This paper studies the apoptosis of human ovarian carcinoma cell Line (SKOV3)
      induced by the nanosecond pulsed electric field (10kV/cm, 100ns, 1 Hz) and its
      effect on intracellular calcium concentration ([Ca2+]i). These cells were doubly
      marked by Annexin V-FITC/PI, and the apoptosis rate was analyzed with flow
      cytometry. After AO/EB staining the morphological changes were observed under
      fluorescent microscope, and their ultrastructural changes were observed under
      scanning electron microscope (SEM). With Fluo-3/AM as calcium fluorescent marker,
      laser scanning confocal microscope (LSCM) was used to detect the effect of nsPEF
      on [Ca2+]i and the source of Ca2+. The results showed that the early apoptosis
      rate of the treatment group was (22.21+/-2.71)%, significantly higher than that
      of the control group (3.04+/-0.44)% (P<0.01). The typical features of apoptotic
      cell have been observed by fluorescent microscope and SEM. It is proved that
      nsPEF can induce apoptosis of SKOV3 cells and result in distinct increase in
      [Ca2+]i (P0.01), which was independent of extracellular calcium concentration
      (P>0.05). Since nsPEF can penetrate cell membrane due to its high frequency
      components, one of the mechanisms of nsPEF-induced apoptosis may be that
      activating intracellular calcium stores can increase the [Ca2+]i, and
      consequently, the apoptotic signal pathway can be induced.

PMID- 19162842
TI  - A dynamic clonal selection immune clustering algorithm.
AB  - According to the basis of clonal selection immune algorithm and hierarchical
      clustering, a dynamic clonal selection immune clustering algorithm is presented,
      which no pre-knowledge is needed. The proposed algorithm bases on antibody
      affinity, to recognize antigen, restrain and merge antibody. By using aiNET
      immune network model, the algorithm mutates location of antibodies, in which the
      mutating rate is dynamically adjusted with inverse proportion to the number of
      immune evolution generations. After dynamic mutation, the similar antibodies are
      merged again, and the same processes repeats until it meets the ending condition.
      Experimental results showed that the proposed algorithm is more coincidental
      reality of clustering and more preferable performance than traditional ones.

PMID- 19162843
TI  - Non-thermal effects of 500MHz - 900MHz microwave radiation on enzyme kinetics.
AB  - Enzymes are essential for the catalysis of biochemical reactions and in the
      regulation of metabolic pathways. They function by greatly accelerating the rate
      of specific chemical reactions that would otherwise be slow. It has been shown
      that extremely low-power microwaves can influence enzyme activity [1-5]. This
      study is focused at investigating the effects of low level microwave exposures
      ranging from 500MHz to 900MHz on L-Lactate Dehydrogenase (LDH) enzyme activity.
      The results obtained revealed the increased bioactivity of the LDH upon microwave
      radiation at two particular frequencies 500MHz and 900MHz.

PMID- 19162844
TI  - Fetal movement quantification by fetal vectorcardiography: a preliminary study.
AB  - Fetal movement is a valuable source of information to monitor the neurological
      development of the fetus and assess fetal health. Currently, fetal movement can
      be assessed by the mother or detected by analysis of ultrasound images. Long-term
      monitoring of movement is complicated with both these methods as maternal self
      assessment has a relatively poor sensitivity and specificity and automatic
      analysis of ultrasound images is not available. Moreover, ultrasound transducers
      transmit energy into the body, potentially endangering fetal health. In this
      paper, an alternative method for fetal movement monitoring is presented. This
      method operates by estimating and analyzing the fetal vectorcardiogram (VCG) from
      non-invasive recordings on the maternal abdomen. The determined fetal movement is
      compared with that assessed from a simultaneously performed ultrasound recording;
      the results of the presented method are consistent with the ultrasound images. In
      addition, the presented method enables quantification of the rotation angles by
      means of analysis of the rotation matrix between consecutive fetal VCGs,
      providing a tool for long-term monitoring of fetal movement with increased
      specificity.

PMID- 19162845
TI  - Estimating the time constant of pitch rVOR by separation of otoliths and
      semicircular canals contributions.
AB  - The rotational vestibulo-ocular reflex (rVOR) contributes to gaze stabilitization
      by compensating head rotational movements sensed by the semicircular canals
      (SCC). The CNS improves the performance of the horizontal rVOR through the so
      called velocity storage mechanism (VSM). However the properties of the VSM in
      response to pitch rotations are less well known. We recorded eye movements evoked
      by whole-body constant-velocity pitch rotations about an earth-horizontal,
      interaural axis in four healthy human subjects. Subjects were tumbled forward,
      and backward, at 60 deg/s for over one minute using a 3D turntable. In these
      conditions also the otoliths contribute to the perception of head rotation
      because they sense the changes in direction of the gravity vector. The vertical
      slow phase velocity (SPV) responses show the typical exponential decay of the
      rVOR and a residual, otolith-driven sinusoidal modulation with a bias. Here the
      estimates of the contributions coming from the otoliths and from the canals are
      based on a linear summation hypothesis. The time constants of the canal-driven
      vertical component of the SPV ranged from 6 to 9 seconds. These values are closer
      to those produced by the SCC alone than the typical 20 s produced by the VSM in
      the horizontal plane, confirming the relatively small contribution of the VSM to
      these vertical responses. We also show that the estimation method, while it may
      be not physiologically accurate, is easy to implement and leads to reliable
      results.

PMID- 19162846
TI  - Detection of ventilatory threshold by an automatic parabolic model.
AB  - This work aims at presenting a method for automatic detection of the ventilatory
      threshold by modeling ventilatory equivalent of oxygen by a parabolic function.
      Thirty healthy male subjects were submitted to a single maximal oxygen uptake
      test, being monitored the ventilatory gas exchange signals. Ventilatory threshold
      by visual inspection, automatic v-slope and parabolic function methods was
      compared. The automatic methods showed no significant differences with visual
      inspection, but the parabolic technique presented higher consistence than v
      slope. Since the parabolic method have low computation cost and is a simple
      method, it can be recommended as an alternative choice to v-slope method.

PMID- 19162847
TI  - Joint angle tracking with inertial sensors.
AB  - Many wearable inertial systems have been used to continuously track human
      movement in and outside of a laboratory. The number of sensors and the complexity
      of the algorithms used to measure position and orientation vary according to the
      clinical application. To calculate changes in orientation, researchers often
      integrate the angular velocity. However, a relatively small error in measured
      angular velocity leads to large integration errors. This restricts the time of
      accurate measurement to a few minutes. We have combined kinematic models designed
      for control of robotic arms with state space methods to directly and continuously
      estimate the joint angles from inertial sensors. These algorithms can be applied
      to any combination of sensors, can easily handle malfunctions or the loss of some
      sensor inputs, and can be used in either a real-time or an off-line processing
      mode with higher accuracy.

PMID- 19162848
TI  - Identification of onset, maximum and termination of obstructive sleep apnoea
      events in single lead ECG recordings.
AB  - Measuring the Apnoea Hypopnoea Index (AHI) is important for determining the
      severity of any apnoea patient. This study presents a method of screening each
      apnoea event separately based on the single lead Electrocardiogram (EGG) signal.
      The whole ECG of a subject was divided into Normal, Onset, OSA-maximum and
      Termination epochs with length of 5 seconds. PSD analysis was used for
      determining the features directly from the ECG. ROC area was calculated to
      determine the discrimination capability of each feature (or power in each
      frequency bin) found by PSD analysis. The maximum ROC area found between Normal
      vs. OSA-maximum was 0.81 in the frequency range of 52-72 Hz. The ROC area and
      significant frequency band for Normal vs. Onset and Normal vs. Termination were
      0.78, 0.78 and 57-65 Hz, 52-66 Hz respectively.

PMID- 19162849
TI  - Feasibility study on driver's stress detection from differential skin temperature
      measurement.
AB  - Prolonged monotonous driving may lower a driver's awareness level as well as
      increasing their stress level due to the compulsion to maintain safe driving,
      which may result in an increased risk of a traffic accident. There is therefore
      an opportunity for technological assessment of driver physiological status to be
      applied in-car, hopefully reducing the incidence of potentially dangerous
      situations. As part of our long-term aim to develop such a system, we describe
      here the investigation of differential skin temperature measurement as a possible
      marker of a driver's stress level. In this study, healthy male (n=18) & female
      (n=7) subjects were investigated under environment-controlled conditions, whilst
      being subjected to simulated monotonous travel at constant speed on a test
      course. We acquired physiological variables, including facial skin temperature
      which consists of truncal and peripheral skin temperatures (Ts) using
      thermography, beat-by-beat blood pressure (BP), cardiac output (CO), total
      peripheral resistance (TPR), and normalized pulse volume (NPV) used as an
      indicator of local peripheral vascular tone. We then investigated the driver's
      reactivity in terms of skin temperatures with this background of cardiovascular
      haemodynamics. We found that the simulated monotonous driving produced a gradual
      drop in peripheral Ts following the driving stress, which, through interpretation
      of the TPR and NPV recordings, could be explained by peripheral sympathetic
      activation. On the other hand, the truncal Ts was not influenced by the stress.
      These findings lead us to suggest that truncal-peripheral differential Ts could
      be used as a possible index indicative of the driver's stress.

PMID- 19162850
TI  - Feature extraction for analysis of ECG signals.
AB  - The automated diagnostic systems employing diverse and composite features for
      electrocardiogram (ECG) signals were analyzed and their accuracies were
      determined. Because of the importance of making the right decision,
      classification procedures classifying the ECG signals with high accuracy were
      investigated. The classification accuracies of mixture of experts (ME) trained on
      composite features and modified mixture of experts (MME) trained on diverse
      features were compared. The inputs of these automated diagnostic systems were
      composed of diverse or composite features (power levels of the power spectral
      density estimates obtained by the eigenvector methods) and were chosen according
      to the network structures. The conclusions of this study demonstrated that the
      MME trained on diverse features achieved accuracy rates which were higher than
      that of the ME trained on composite features.

PMID- 19162851
TI  - Spectral analysis on the microcirculatory laser Doppler signal at the acupuncture
      point.
AB  - We aimed to characterize the frequency spectra of skin blood flow signals
      simultaneously recorded at Hoku, an important acupoint in oriental medicine, and
      two nearby nonacupoints to understand the underlying physiological mechanism of
      acupuncture points. ECG and laser Doppler flowmetry signals were measured
      simultaneously. A four-level Haar wavelet transform was applied to the measured
      20-minute LDF signals, and periodic oscillations with five characteristic
      frequency peaks were obtained within the following frequency bands: 0.0095-0.021,
      0.021-0.052, 0.052-0.145, 0.145-0.6, and 0.6-1.6 Hz (defined as FR1-FR5),
      respectively. The power in FR3 was significantly larger at Hoku than at the two
      nonacupoints. Spectral analysis of the flux signal revealed that one of the major
      microcirculatory differences between acupoints and nonacupoints was in the
      different myogenic responses of their vascular beds. This information may aid the
      development of a method to noninvasively study the microcirculatory
      characteristics of the acupoint.

PMID- 19162852
TI  - On the detection of Premature Ventricular Contractions.
AB  - Premature Ventricular Contractions (PVC) are a cardiac arrhythmia that can be
      associated with an increased risk of adverse cardiac events such as ventricular
      arrhythmias and sudden death. Therefore, the characterization of this arrhythmia
      becomes crucial in the early diagnosis and prevention of possible life
      threatening cardiac diseases. In this paper a new approach for automatic
      detection of PVCs is presented, based on morphological derivatives and
      information theory techniques. Using these approaches a set of patient invariant
      features is introduced. Sensibility and specificity results (respectively, 96.35%
      and 99.15%) show the potential of the algorithm when applied to the MIT-BIH
      Arrhythmia database.

PMID- 19162853
TI  - Clustering and modeling of EEG coherence features of Alzheimer's and mild
      cognitive impairment patients.
AB  - Using multiple discriminant analysis (MDA) and k-means clustering, coherence
      features extracted from the EEGs of a group of 56 subjects were analyzed to
      assess how feasible an automated coherence-based pattern recognition system that
      detects Alzheimer's disease (AD) would be. Sixteen of the subjects were AD
      patients, 24 were mild cognitive impairment (MCI) patients while 16 were age
      matched controls. With MDA, an overall classification rate (CR) of 84% was
      obtained for AD vs. MCI vs. Controls classifications. The high CR implies that it
      is possible to distinguish between the three groups. The coherence features were
      also statistically analyzed to derive a neural model of AD and MCI, which
      indicated that patients with AD may have a greater number of damaged cortical
      fibers than their MCI counterparts, and furthermore, that MCI may be an
      intermediary step in the development of AD.

PMID- 19162854
TI  - Increase in regularity and decrease in variability seen in electroencephalography
      (EEG) signals from alert to fatigue during a driving simulated task.
AB  - Driver fatigue is a prevalent problem and a major risk for road safety accounting
      for approximately 20-40% of all motor vehicle accidents. One strategy to prevent
      fatigue related accidents is through the use of countermeasure devices. Research
      on countermeasure devices has focused on methods that detect physiological
      changes from fatigue, with the fast temporal resolution from brain signals, using
      the electroencephalogram (EEG) held as a promising technique. This paper presents
      the results of nonlinear analysis using sample entropy and second-order
      difference plots quantified by central tendency measure (CTM) on alert and
      fatigue EEG signals from a driving simulated task. Results show that both sample
      entropy and second-order difference plots significantly increases the regularity
      and decreases the variability of EEG signals from an alert to a fatigue state.

PMID- 19162855
TI  - Linear discriminant analysis of MUAP scalograms.
AB  - The paper presents a new approach to the computer aided diagnostic systems for
      the needs of quantitative electromyography. The approach is based on the analysis
      of wavelet scalograms of the motor unit action potentials calculated on the basis
      of 4th order Symlet wavelet. The scalograms provide the vector consisting of six
      features describing the state of a muscle that can be reduced to the two features
      with use of Linear Discriminant Analysis. Consequently, the healthy, myogenic and
      neurogenic cases can be successfully classified using the linear methods.

PMID- 19162856
TI  - An adaptive filter bank for motor imagery based Brain Computer Interface.
AB  - Brain Computer Interface (BCI) provides an alternative communication and control
      method for people with severe motor disabilities. Motor imagery patterns are
      widely used in Electroencephalogram (EEG) based BCIs. These motor imagery
      activities are associated with variation in alpha and beta band power of EEG
      signals called Event Related Desynchronization/synchronization (ERD/ERS). The
      dominant frequency bands are subject-specific and therefore performance of motor
      imagery based BCIs are sensitive to both temporal filtering and spatial
      filtering. As the optimum filter is strongly subject-dependent, we propose a
      method that selects the subject-specific discriminative frequency components
      using time-frequency plots of Fisher ratio of two-class motor imagery patterns.
      We also propose a low complexity adaptive Finite Impulse Response (FIR) filter
      bank system based on coefficient decimation technique which can realize the
      subject-specific bandpass filters adaptively depending on the information of
      Fisher ratio map. Features are extracted only from the selected frequency
      components. The proposed adaptive filter bank based system offers average
      classification accuracy of about 90%, which is slightly better than the existing
      fixed filter bank system.

PMID- 19162857
TI  - An analysis of EEG when acupuncture with wavelet entropy.
AB  - Wavelet energy entropy derived from wavelet multi-revolution decomposition,
      reconstruction and Shannon entropy can signify the complexity of unsteady EEG
      signals in both time domain and frequency domain. Firstly, the paper gives an
      introduction of the methods about wavelet energy entropy. Then the EEG signals
      when acupuncture is analyzed and some conclusions are addressed by using wavelet
      energy entropy, relative wavelet energy entropy and the time evolution of them.

PMID- 19162858
TI  - Identification of independent biological sensors-electromyogram example.
AB  - To ensure that no biological event that may be important is missed, redundancy of
      sensors is provided. While this is useful, there are shortcomings when there is
      need to separate the signals from different sources using blind source separation
      techniques. An example of such a situation is over-complete surface
      electromyogram (sEMG) recording. Techniques such as principal component analysis
      (PCA) and entropy measures are used to identify the suitable channels. The
      shortcomings in these are the need for prior estimation of the number of
      channels. This paper has used the determinant of the global matrix of the
      mixtures to determine the number of independent sources in a mixture. The results
      indicate that the technique is able to distinguish between dependent and
      independent channels and this may be applied for determining the number of
      independent sources. The applications of this include data reduction by
      identifying redundant data, and for pre-processing of the data prior to use of
      any data classification techniques.

PMID- 19162859
TI  - Automated diagnostic method supporting EMG examination.
AB  - A method of diagnosing neural-muscular diseases via Fourier spectral analysis is
      presented in the paper. Application of this analysis allowed for obtaining a
      series of spectral features. This resulted in a selection of a discriminant
      ensuring the best sensitivity of the new method, better than the QEMG method used
      in the clinical practice. Software implementation of the spectral discriminant
      enabled creation of a computer diagnostic tool supporting EMG examination. The
      method is fully automated.

PMID- 19162860
TI  - Frequency domain approach for activity classification using accelerometer.
AB  - Activity classification was performed using MEMS accelerometer and wireless
      sensor node for wireless sensor network environment. Three axes MEMS
      accelerometer measures body's acceleration and transmits measured data with the
      help of sensor node to base station attached to PC. On the PC, real time
      accelerometer data is processed for movement classifications. In this paper,
      Rest, walking and running are the classified activities of the person. Both time
      and frequency analysis was performed to classify running and walking. The
      classification of rest and movement is done using Signal magnitude area (SMA).
      The classification accuracy for rest and movement is 100%. For the classification
      of walk and Run two parameters i.e. SMA and Median frequency were used. The
      classification accuracy for walk and running was detected as 81.25% in the
      experiments performed by the test persons.

PMID- 19162861
TI  - Addressing source separation and identification issues in surface EMG using blind
      source separation.
AB  - Source separation and identification is one of the challenging areas in the bio
      signal processing. The processing of Electromyographic (EMG) signals can be
      viewed as the identification and separation of a series of overlapping sources of
      muscle activity with slowly varying source distribution and/or levels of
      activity. Blind source separation (BSS) techniques such as independent component
      analysis (ICA) lend themselves well to the analysis of such problems. The
      problem, however, still remains largely ill-posed even through the use of
      powerful assumptions such as those posed in ICA and other such techniques. It is
      generally the case in EMG signals that a certain level of a priori knowledge is
      available on the spatio-temporal and/or frequency distribution of the activities
      of interest, based on neurophysiological expectations. Here we describe
      limitations and applications of BSS on surface EMG. The problems we consider
      include the analysis of facial sEMG recordings during vowel utterance and
      analysis of hand EMG during finger and wrist movements.

PMID- 19162862
TI  - Atrial fibrillation detection using stationary wavelet transform analysis.
AB  - Atrial fibrillation (AF) is a common cardiac arrythmia that is usually developed
      for elder people with aging. AF may result in complications such as chest pain or
      even heart failure in later stage. Based on the characteristics of surface ECG,
      AF can be detected by several methods. A particular investigation on the
      fibrillatory waveform reveals the inherent structure of AF signals. As opposed to
      traditional frequency domain methods, we utilize the stationary wavelet transform
      to extract the information from ECG signal which differentiates AF and non-AF
      cases based on some feature extraction and selection processes. A linear
      classifier is then designed for computational efficiency. The proposed method
      eliminates the need for QRST cancellation step which is required for frequency
      domain methods and provides a more systematic approach for AF detection.
      Extensive experiments are tested on signals from the MIT-BIH Atrial Fibrillation
      Database to show the superior performance of the proposed algorithm.

PMID- 19162863
TI  - Automatic classification of inspiratory flow limitation assessed non-invasively
      during sleep.
AB  - Detection of inspiratory flow limitation (IFL) is being recognized of increasing
      importance in order to diagnose pathologies related to sleep disordered
      breathing. Currently, IFL is usually identified with the help of invasive
      esophageal pressure measurement, still considered the gold-standard reference to
      assess respiratory effort. But the invasiveness of esophageal pressure
      measurement and its impact on sleep discourages its use in clinical routine. In
      this study, a new noninvasive automatic system is proposed for objective IFL
      classification. First, an automatic annotation system for IFL based on
      pressure/flow relationship was developed. Then, classifiers (Support Vector
      Machines and adaboost classifiers) were trained with these gold-standard
      references in order to objectively classify breaths non-invasively, solely based
      on the breaths' flow contours. The new non-invasive automatic classification
      system seems to be promising, as it achieved a sensitivity of 0.92 and a
      specificity of 0.89, outperforming prior classification results obtained by human
      experts.

PMID- 19162864
TI  - Real-time automated neural-network sleep classifier using single channel EEG
      recording for detection of narcolepsy episodes.
AB  - Conventional sleep staging and classification methods involve complicated
      settings to acquire multiple electrophysiological signals for extended recording
      durations, followed by specialists' analysis which is a time consuming exercise.
      These procedures need to be carried out in sleep clinics and are not suitable for
      applications based on real-time sleep monitoring and analysis. In this paper, a
      real-time sleep staging and classification technique is proposed using single EEG
      channel based on an artificial neural network classifier. This method is
      optimized to run on portable processing platforms with limited processing
      capabilities.

PMID- 19162865
TI  - Respiratory rate detection algorithms by photoplethysmography signal processing.
AB  - Photoplethysmography (PPG) offers the clinically meaningful parameters, such as,
      heart rate, and respiratory rate. In this study, we presented three respiratory
      signal detection algorithms using photoplethysmography raw data generated from
      commercial PPG sensor: (1)Min-Max (2)Peak-to-Peak (3)Pulse Shape. As reference
      signal, nasal sensor signal was acquired simultaneously and compared and
      analyzed. We used two types of moving average filtering technique to process
      three PPG parameters. In laboratory experiment, 6 subjects' PPG signals were
      measured when they respire ten and fifteen, and arbitrary times per minute. From
      the results, following conclusions were drawn. Min-Max and Peak-to-Peak
      algorithms perform better than Pulse shape algorithm. They can be used to detect
      respiratory rate. But, Pulse Shape algorithm was accurate for subject 4 only.
      More experimental data is necessary to improve the accuracy and reliability.

PMID- 19162866
TI  - Automatic ballistocardiogram (BCG) beat detection using a template matching
      approach.
AB  - This paper suggests a beat detection method for ballistocardiogram (BCG) from an
      unconstrained cardiac signal monitoring devices. A fiducial peak point of BCG is
      an I-J-K complex which corresponds with ventricle contraction and
      Electrocardiogram (ECG) QRS complex. The goal of the method is extraction of J
      peak without ECG synchronization. The detection method is based on a "template
      matching" rule evaluated using a correlation function in a local moving-window
      procedure. The total beat detection algorithm operates in two stages, template
      definition stage and beat detection stage with defined template in previous
      stage. In the first stage, the BCG template is constructed by the expert with an
      empirical analysis of BCG signal and measurement device. In the second stage, the
      correlation function calculates an accuracy of template with BCG signal using a
      local moving-window. The data analysis has been performed on the subjects tested
      at Seoul National University Hospital Sleep Medicine Center and presents 95.16%
      of sensitivity and 94.76% of positive predictivity value for the J peak
      detection.

PMID- 19162867
TI  - A comparison between a matrix-based and a region-based P300 speller paradigms for
      brain-computer interface.
AB  - A brain-computer interface (BCI) is a system that conveys messages and commands
      directly from the human brain to a computer. The BCI system described in this
      work is based on P300 wave. The P300 is a positive peak of an event-related
      potential (ERP) that happens 300 ms after a stimulus. One of the most well-known
      and widely-used P300 applications is P300 speller designed by Farwell-Donchin in
      1988. The Farwell-Donchin paradigm has been a benchmark in P300 BCI. In this
      paradigm, a 6x6 matrix of letters and numbers is displayed and subject focuses on
      a target character while rows and columns of characters flash. By detecting P300
      for one row and one column, the target character can be identified. In this
      paper, it is shown that there is a human perceptual error in Farwell-Donchin
      paradigm. To remove this error, a new region-based paradigm is presented. Using
      experimental results, it is shown that the new paradigm has several advantages
      and it achieves a better accuracy compared to the Farwell-Donchin paradigm.

PMID- 19162868
TI  - Automatic sleep stage classification based on EEG signals by using neural
      networks and wavelet packet coefficients.
AB  - Currently in the world there is an alarming number of people who suffer from
      sleep disorders. A number of biomedical signals, such as EEG, EMG, ECG and EOG
      are used in sleep labs among others for diagnosis and treatment of sleep related
      disorders. The usual method for sleep stage classification is visual inspection
      by a sleep specialist. This is a very time consuming and laborious exercise.
      Automatic sleep stage classification can facilitate this process. The definition
      of sleep stages and the sleep literature show that EEG signals are similar in
      Stage 1 of non-rapid eye movement (NREM) sleep and rapid eye movement (REM)
      sleep. Therefore, in this work an attempt was made to classify four sleep stages
      consisting of Awake, Stage 1 + REM, Stage 2 and Slow Wave Stage based on the EEG
      signal alone. Wavelet packet coefficients and artificial neural networks were
      deployed for this purpose. Seven all night recordings from Physionet database
      were used in the study. The results demonstrated that these four sleep stages
      could be automatically discriminated from each other with a specificity of 94.4
      +/- 4.5%, a of sensitivity 84.2+3.9% and an accuracy of 93.0 +/- 4.0%.

PMID- 19162869
TI  - A comparative study of the performance of different spectral estimation methods
      for classification of mental tasks.
AB  - In this paper we compare three different spectral estimation techniques for the
      classification of mental tasks. These techniques are the standard periodogram,
      the Welch periodogram and the Burg method, applied to electroencephalographic
      (EEG) signals. For each one of these methods we compute two parameters: the mean
      power and the root mean square (RMS), in various frequency bands. The
      classification of the mental tasks was conducted with a linear discriminate
      analysis. The Welch periodogram and the Burg method performed better than the
      standard periodogram. The use of the RMS allows better classification accuracy
      than the obtained with the power of EEG signals.

PMID- 19162870
TI  - Constrained temporal extraction of the atrial rhythm in Atrial Fibrillation
      episodes.
AB  - The extraction of the Atrial Activity from the Ventricular Activity in Atrial
      Fibrillation episodes is a must for clinical analysis. We follow the semi Blind
      Source Extraction S-BSE approach to solve the problem. The proposed algorithm
      modifies the BSE contrast function to satisfy the prior knowledge about the
      spectral content of the atrial signal. The introduction of this prior allows
      obtaining a new algorithm with the following advantages: it allows the extraction
      of only the atrial component and it improves the quality of the recovered atrial
      signal in terms of spectral concentration as we show in the results.

PMID- 19162871
TI  - Ischemia detection via ECG using ANFIS.
AB  - An adaptive neuro-fuzzy interface system (ANFIS) classifier was used for
      automated detection of ischemic episodes resulting from ST-T segment elevation or
      depression. The performance of the method was measured using the European ST-T
      database. In particular, the performance was measured in terms of beat by- beat
      ischemia detection and in terms of the detection of ischemic episodes. The
      algorithm used to cluster and then train the ANFIS classifier. The resulting
      ANFIS is capable of detecting ischemia independent of the lead used. It was found
      that the average ischemia episode detection sensitivity is 88.62% and specificity
      is 99.65%. This method can be used in electrocardiogram (ECG) processing in cases
      where reliable detection of ischemic episodes is desired as in the case of
      critical care units (CCUs).

PMID- 19162872
TI  - A computationally light classification method for mobile wellness platforms.
AB  - The core of activity recognition in mobile wellness devices is a classification
      engine which maps observations from sensors to estimated classes. There exists a
      vast number of different classification algorithms that can be used for this
      purpose in the machine learning literature. Unfortunately, the computational and
      space requirements of these methods are often too high for the current mobile
      devices. In this paper we study a simple linear classifier and find,
      automatically with SFS and SFFS feature selection methods, a suitable set of
      features to be used with the classification method. The results show that the
      simple classifier performs comparable to more complex nonlinear k-Nearest
      Neighbor Classifier. This depicts great potential in implementing the classifier
      in small mobile wellness devices.

PMID- 19162873
TI  - A study of composite electrode-tissue impedance.
AB  - Electrical impedance tomography has been used in the medical environment for many
      years. Recently it has been used for brain function imaging. This type of
      technology uses a large number of electrodes on the scalp, examples in the
      literature ranging from 8 to 64. In this paper, the composite impedance of the
      electrode in contact with tissue is investigated. An experimental method has been
      developed to enable the use of a commercial impedance analyzer in compliance with
      medical safety standards. The magnitude and long-term stability of the composite
      impedance of the electrode-tissue system is found to be greatly dependent on the
      type of electrodes used.

PMID- 19162874
TI  - 3D electric impedance tomography reconstruction on multi-core computing
      platforms.
AB  - This manuscript presents results relative to the optimization of 3D impedance
      tomography reconstruction algorithms for execution on multi-core computing
      platforms. Speed-ups obtainable by the use of modern computing architectures and
      by an optimized implementation allow the use of much finer FEM meshes in the
      forward model, leading ultimately to a better image quality. We formulate the
      reconstruction as widely common in the EIT community: as a non-linear, least
      squares, Tikhonov regularized, discrete inverse problem. The forward model is
      based on a FEM solver that implements the Complete Electrode Model. By profiling
      a plain but careful MATLAB implementation of such an algorithm, we find that, in
      problems with mesh sizes in the order of 100.000 nodes, typically 95% of the
      computing time is spent in solving the forward problem and in computing the
      Jacobian matrix from the forward solutions. We have focused on optimizing the
      execution of these two functions, and we report relative results. On an octal
      Xeon 5355 based PC, on problems with forward meshes with a number of nodes in the
      range of 59,000 nodes to 146,000 nodes, the optimized algorithm has a speed-up of
      up to 7 times compared to an equivalent MATLAB implementation that makes use of
      the multithreading capabilities of the platform.

PMID- 19162875
TI  - Arbitrary geometry patient interfaces for breast cancer detection and monitoring
      with electrical impedance tomography.
AB  - Electrical impedance tomography (EIT) is a promising technology enabling the
      detection or observation of many biological processes. This is typically
      accomplished by applying currents at known locations on an outer surface (in this
      case skin) and measuring voltages at other locations. This information is then
      used to determine electrical properties of tissue found between the electrodes by
      solving the associated Laplace equation. Such problems depend upon knowing the
      exact boundary conditions (BC). Unfortunately BCs are not always easily
      determined and approximations are accepted out of necessity due to problem
      complexity or time constraints. The EIT group at Dartmouth College has developed
      two new patient interfaces for breast cancer detection and monitoring both of
      which speed acquisition time and allow for precision BC information in natural
      and arbitrary geometries. Preliminary experimental results are presented.

PMID- 19162876
TI  - A new impedance imaging system and dipole basis reconstruction method.
AB  - A number of studies have pointed to a link between the presence of breast cancer
      and a larger than normal tissue electrical admittance in the affected area. This
      phenomenon could make electrical impedance-based imaging a practical asset to
      breast cancer screening. In this paper image reconstruction algorithms are
      developed and evaluated for use with an impedance-based imaging system
      constructed at The George Washington University. The system, which is targeted
      for use in breast cancer screening, is profiled. Computer simulation-based
      results for the two reconstruction approaches are shown and evaluated.

PMID- 19162877
TI  - Monitoring retroperitoneal bleeding model of piglets by electrical impedance
      tomography.
AB  - To investigate continuous monitoring capacity of electrical impedance tomography
      (EIT) for retroperitoneal bleeding, studies were carried out on six anesthetized
      piglet's bleeding model produced by injecting anticoagulated blood into renal
      region. For each subject, total blood of about 200 ml was injected within time
      periods ranging from tens of minutes to several hours. The simulated bleeding
      processes were detected and monitored by EIT system with sixteen electrodes at a
      rate of one image per second. EIT images were reconstructed by dynamic back
      projection algorithm. The results showed that impedance changes caused by
      bleeding could be revealed by EIT images.

PMID- 19162878
TI  - Preliminary research on monitoring of cerebral ischemia using electrical
      impedance tomography technique.
AB  - More than half of the stroke patients are cause by cerebral ischemia/ hypoxia,
      and it is by no means an easy affairs to detect ischemic tissue when it is
      rescuable by drug intervention using traditional imaging technique. The purpose
      of this paper is to testify the feasibility of monitoring cerebral ischemia. By a
      newly developed high precision data acquisition system and specially configured
      imaging method, a series of imaging monitoring experiments were performed on 8
      Chinese local rabbits, who have been induced with cortical ischemia by
      photochemical method. This method of induce ischemia was confirmed by
      histopathological examination. The imaging results show that impedance in target
      area increased rapidly 7-20 minutes after the beginning of the irradiation during
      ischemia induce process, and will still change rapidly during and after the
      induction of ischemia. Unexpected impedance fluctuations were also seen in 6 out
      of 8 animals during this process. Therefore, EIT monitoring technique proved to
      be a rapid and sensitive way to detect cerebral ischemia in very earlier stage.

PMID- 19162879
TI  - Imaging forearm blood flow with pulse-ox gated electrical impedance tomography.
AB  - Assessing peripheral vasculature health has the potential to impact clinical
      decision making in terms of treating patients with cardiovascular disease. The
      electrical conductivity of certain tissue regions within the forearm change as
      blood vessels undergo pulsatile dilation in synchrony with the beating of the
      heart. We use dynamic electrical impedance tomography (EIT) gated to the peak of
      a pulse oxymetry plethysmography waveform to image this temporally varying
      spatial conductivity. A phantom imaging experiment is presented showing that
      small conductivity changes of less than 1 mm are detectable using the developed
      dynamic EIT system. This system is used to image a volunteer's forearm during
      resting cardiovascular activity. Similar structures are observed in the
      plethysmography trace and the temporally varying conductivity. Spectral analysis
      shows that the maximum amplitude is occurring at frequencies of 1.19 Hz and 1.21
      Hz for the plethysmography trace and conductivity trace, respectively. This
      preliminary data suggests that EIT may be sensitive enough to visualize cardiac
      based pulsatility in the peripheral vessels of the forearm.

PMID- 19162880
TI  - A method for semiautomatic tracing and morphological measuring of neurite
      outgrowth from DIC sequences.
AB  - We present a method for semi-automatic tracing and measuring of neurite outgrowth
      from time-lapse sequences of digital Nomarski micrographs. The algorithm is based
      on neurite ridge extraction and characterization from a single frame, followed by
      an automatic neurite tracking and measurement along the image sequence. Our
      method was tested with two sequences one containing 29 and other with 77 frames
      taken at intervals of 2 min. Our method rendered comparable length measurements
      but better time performance than measurements made by use of certain public
      software.

PMID- 19162881
TI  - A study of shape distributions for estimating histologic grade.
AB  - Breast cancers can be histologically categorized (graded) based upon their
      architectural patterns and cellular types. Inaccurate histologic grading can
      result in inappropriate treatment for a given patient. Computational analysis of
      breast cancers offers an operator-independent method for histologic grading that
      should enhance grading reliability. We present the initial efforts to develop
      computational technologies that may be used to automatically and objectively
      estimate the histologic grade of breast cancer tumors. The approach utilizes
      image processing and shape analysis of imaged histologic sections. Our work is
      based on the hypothesis that cellular structures found in breast cancer tumors
      can be transformed into distinct high-resolution shape distributions using
      geometric measures from stochastic geometry. The resulting shape distributions
      define well-populated regions of the associated high-dimensional space. Mapping
      an unknown breast cancer sample into this high-D space and determining to which
      region it belongs will allow for the automatic estimation of its histologic
      grade.

PMID- 19162882
TI  - Image processing system for ultrasound images of the eye.
AB  - Closed Angle Glaucoma causes an increase in fluid pressure in the eye due to
      decreased fluid flow between the iris and the cornea. To diagnose Glaucoma,
      ultrasound images of the eye are taken and a technician studies the images and
      takes measurements. This process is time consuming, and results vary among
      technicians. In a previous paper, we developed an image processing algorithm to
      extract several key landmark features in the iris. In this paper, we extend this
      algorithm to calculate the complete set of diagnostic parameters from ultrasound
      biomicroscopy. A robust algorithm is described to calculate the parameters which
      describe the thickness of iris; ID1, ID2, and ID3. The method is tested on 89
      clinical images and compared to the values identified by the technician. Results
      indicate good agreement in 97% of cases.

PMID- 19162883
TI  - Web based brain volume calculation for magnetic resonance images.
AB  - Brain volume calculations are crucial in modern medical research, especially in
      the study of neurodevelopmental disorders. In this paper, we present an algorithm
      for calculating two classifications of brain volume, total brain volume (TBV) and
      intracranial volume (ICV). Our algorithm takes MRI data as input, performs
      several preprocessing and intermediate steps, and then returns each of the two
      calculated volumes. To simplify this process and make our algorithm publicly
      accessible to anyone, we have created a web-based interface that allows users to
      upload their own MRI data and calculate the TBV and ICV for the given data. This
      interface provides a simple and efficient method for calculating these two
      classifications of brain volume, and it also removes the need for the user to
      download or install any applications.

PMID- 19162884
TI  - Automatic segmentation of intracranial hematoma and volume measurement.
AB  - In this paper, a two-step segmentation method is developed for segmenting the
      hematoma area from brain CT images. The volume of hematoma area is calculated
      after the segmentation. During the second segmentation process, the method of two
      dimensional entropy is introduced to separate hematoma. In using the method of
      two-dimensional entropy, most important is to find the optional threshold which
      can be achieved by an improved genetic algorithm (GA) i.e. hierarchical genetic
      algorithm (HGA). HGA is more efficient than simple GA in overcoming the
      shortcoming of standard GA in local optimal solution and low precision
      convergence. An experiment is designed to test the effectiveness of automatic
      segmentation. The results prove that the precision of automatic segmentation is
      better than artificial segmentation, and the clinical needs are met.

PMID- 19162885
TI  - ITAC volume assessment through a Gaussian hidden Markov random field model-based
      algorithm.
AB  - In this paper, a semi-automatic segmentation method for volume assessment of
      Intestinal-type adenocarcinoma (ITAC) is presented and validated. The method is
      based on a Gaussian hidden Markov random field (GHMRF) model that represents an
      advanced version of a finite Gaussian mixture (FGM) model as it encodes spatial
      information through the mutual influences of neighboring sites. To fit the GHMRF
      model an expectation maximization (EM) algorithm is used. We applied the method
      to a magnetic resonance data sets (each of them composed by T1-weighted, Contrast
      Enhanced T1-weighted and T2-weighted images) for a total of 49 tumor-contained
      slices. We tested GHMRF performances with respect to FGM by both a numerical and
      a clinical evaluation. Results show that the proposed method has a higher
      accuracy in quantifying lesion area than FGM and it can be applied in the
      evaluation of tumor response to therapy.

PMID- 19162886
TI  - Detection of chromosomal abnormalities with multi-color fluorescence in situ
      hybridization (M-FISH) imaging and multi-spectral wavelet analysis.
AB  - Multicolor karyotyping technologies, including both multi-color fluorescence in
      situ hybridization (MFISH) [l] and spectral karyotyping (SKY) [2], are recently
      developed molecular cytogenetic techniques for rapid visualization of genornic
      aberrations at sub-cellular level. Multi-color karyotyping techniques are based
      on multi-spectral microscopic imaging in combination with high resolution
      molecular probes developed in genomics, which have been successhlly used in
      postnatal and cancer cytogenetics. Despite their promise, the current techniques
      are not reliable for clinical use [3]. Routine clinical application of these
      techniques for molecular cytogenetic diagnosis has been hampered by several
      technical limitations. A primary problem is the pixel by pixel classification of
      chromosomes from the multi-color image representations. In this work, we propose
      a new wavelet transform for multi-color image representation, which can
      effectively reduce the redundancy between multi-color images such that the
      classification accuracy can be improved. The algorithm was validated by testing
      on a database containing chromosome images obtained from a variety of M-FISH
      probes.

PMID- 19162887
TI  - Color multiscale texture classification of hysteroscopy images of the
      endometrium.
AB  - The objective of this study was to investigate the diagnostic performance of a
      Computer Aided Diagnostic (CAD) system based on color multiscale texture analysis
      for the classification of hysteroscopy images of the endometrium, in support of
      the early detection of gynaecological cancer. A total of 416 Regions of Interest
      (ROIs) of the endometrium were extracted (208 normal and 208 abnormal) from 45
      subjects. RGB images were gamma corrected and were converted to the YCrCb color
      system. The following texture features were extracted from the Y, Cr and Cb
      channels: (i) Statistical Features (SF), (ii) Spatial Gray Level Dependence
      Matrices (SGLDM), and (iii) Gray Level Difference Statistics (GLDS). The
      Probabilistic Neural Network (PNN), statistical learning and the Support Vector
      Machine (SVM) neural network classifiers were also applied for the investigation
      of classifying normal and abnormal ROIs in different scales. Results showed that
      the highest percentage of correct classification (%CC) score was 79% and was
      achieved for the SVM models trained with the SF and GLDS features for the 1x1
      scale. This %CC was higher by only 2% when compared with the CAD system
      developed, based on the SF and GLDS feature sets computed from the Y channel
      only. Further increase in scale from 2x2 to 9x9, dropped the %CC in the region of
      60% for the SF, SGLDM, and GLDS, feature sets, and their combinations.
      Concluding, a CAD system based on texture analysis and SVM models can be used to
      classify normal and abnormal endometrium tissue in difficult cases of
      gynaecological cancer. The proposed system has to be investigated with more cases
      before it is applied in clinical practise.

PMID- 19162888
TI  - Color image processing and content-based image retrieval techniques for the
      analysis of dermatological lesions.
AB  - This paper presents color image processing methods for the analysis of
      dermatological images in the context of a content-based image retrieval (CBIR)
      system. Tests were conducted on the classification of tissue components in skin
      lesions, in terms of necrotic tissue, fibrin, granulation, and mixed composition.
      The images were classified based on color components by an expert dermatologist
      following a black-yellow-red model. Indexing and retrieval of images were
      performed based on texture information obtained from the red, green, blue, hue,
      and saturation components of the color images. The performance of the CBIR system
      was measured in terms of precision and recall. Initial results demonstrate the
      potential of the proposed methods with the best precision result of 70% obtained
      for the characterization of mixed tissue composition.

PMID- 19162889
TI  - Development of blood vessel viewer using multi spectral imaging technology.
AB  - Using multi spectral imaging technology, which enable us to simultaneously obtain
      spatial and wavelength information, we have newly developed blood vessel viewer.
      Our device is composed of the light source, the lens or the endoscope, the
      optical device, CCD camera, and PC. As an evaluation of our device, we measured
      the skin diffuse reflectance spectrum of the human hand. The blood vessel
      observed by our device was corresponding to an anatomy finding. However, even if
      Principal Component Analysis was used, the reflection of horny was not able to be
      removed completely.

PMID- 19162890
TI  - Hyperspectral imaging and diagnosis of intestinal ischemia.
AB  - Intestinal ischemia results from a variety of disorders that cause insufficient
      blood flow to the intestine. The type and prognosis of ischemic injury depends on
      the blood vessels involved, the underlying medical condition, and the swiftness
      with which the problem is brought to medical attention for diagnosis and
      treatment. Hyperspectral imaging has developed as a compact imaging and
      spectroscopic tool that can he used for different applications including medical
      diagnostics. In this paper, the application of hyperspectral imaging as a visual
      supporting tool to detect the intestinal ischemia during surgeries is evaluated.
      It will he useful for rapid diagnosing tissue abnormalities. The images are
      captured using an infrared hyperspectral camera (900-1700m). Using hyperspectral
      images, the spectral signatures for normal intestine, clamped ischemic intestine
      and other abdominal organs are created. The high-dimensional data are compressed
      using wavelet transform and classified using support vector machine (SVM). The
      performance of this method is evaluated for detection of ischemic intestine in an
      abdominal surgery on a pig. The criteria to evaluate performance are based on
      false negative rate (FNR) and false positive rate (FPR). This technique is able
      to detect ischemic intestine with a small FPR and FNR.

PMID- 19162891
TI  - Classification of endoscopic capsule images by using color wavelet features,
      higher order statistics and radial basis functions.
AB  - This paper presents a system to support medical diagnosis and detection of
      abnormal lesions by processing capsule endoscopic images. Endoscopic images
      possess rich information expressed by texture. Texture information can be
      efficiently extracted from medium scales of the wavelet transform. The set of
      features proposed in this paper to code textural information is named color
      wavelet covariance (CWC). CWC coefficients are based on the covariances of second
      order textural measures, an optimum subset of them is proposed. Third and forth
      order moments are added to cope with distributions that tend to become non
      Gaussian, especially in some pathological cases. The proposed approach is
      supported by a classifier based on radial basis functions procedure for the
      characterization of the image regions along the video frames. The whole
      methodology has been applied on real data containing 6 full endoscopic exams and
      reached 95% specificity and 93% sensitivity.

PMID- 19162892
TI  - DC information preservation for cardiopulmonary monitor utilizing CW Doppler
      radar.
AB  - Direct conversion RF receivers introduce large DC offsets, reducing the dynamic
      range of the baseband signal. Coupled with the relatively small time varying
      signals in human vital sign monitoring using CW Doppler radar, extraction of
      cardio-pulmonary information becomes difficult. Previous DC offset compensation
      techniques utilizing AC coupling have proven detrimental to the performance of
      the system and the integrity of the low-frequency cardiopulmonary signals. A
      proposed system utilizing digitally controlled voltage feedback and center
      finding preserves the important DC information for optimal extraction of phase
      information in the quadrature system.

PMID- 19162893
TI  - Radiation characteristics of ingested wireless device at frequencies from 430 MHz
      to 3 GHz.
AB  - In order to assess the compliance of high frequency ingested wireless devices
      (IWD) within the safety guidelines worldwide, the biological effects and the
      radiation efficiency of the IWD in a realistic human body model were studied
      using the Finite-Difference Time-Domain (FDTD) method. Simulations were carried
      out for three orientations of the IWD at seven positions in the human body model.
      Specific Absorption Rate (SAR), temperature rise, near field and far field
      characteristics were analyzed at frequencies from 430 MHz to 3 GHz. Results
      showed that the radiation intensity outside the body decreased with frequency.
      Furthermore, the orientation and position of the IWD, which gave maximum
      radiation efficiency, was frequency dependent. In our experiment, when the IWD
      was located at the front-most and back-most positions of the small intestine, the
      electric intensity outside the human body was maximum and minimum, respectively.
      The position influences the radiation efficiency of the IWD more than its
      orientation.

PMID- 19162894
TI  - Implementation of a telemetry system for neurophysiological signals.
AB  - With an ever increasing need for assessment of neurophysiological activity in
      connection with injury and basic research, the demand for an efficient and
      reliable data acquisition system rises. Brain-machine interfaces is one class of
      such systems that targets the central nervous system. A necessary step in the
      development of a brain-machine interface is to design and implement a reliable
      and efficient measurement system for neurophysiological signals. The use of
      telemetric devices increases the flexibility of the devices in terms of subject
      mobility and unobtrusiveness of the equipment. In this paper, we present a
      complete system architecture for a wearable telemetry system for the acquisition
      of neurophysiological data. The system has been miniaturized and implemented
      using surface-mount technology. System performance has been successfully verified
      and bottlenecks in the architecture have been identified.

PMID- 19162895
TI  - Application for the wearable heart activity monitoring system: analysis of the
      autonomic function of HRV.
AB  - The wearable patch-style heart activity monitoring system (HAMS) which was used
      for recording ECG signal in this study is self-developed. This electrode design
      helps the non-restricted, non-aware and non-invasive ECG measurement. The
      modified bipolar electrode is convenient in use because it is designed for easy
      attachment and detachment with ECG measuring module by snap button. Besides, it
      minimizes EMI by removing the cables. In the same subjects who were exposed under
      stress and non-stress, the questionnaire was given out, the amount of the stress
      hormone was measured by blood test and the ECG signal was recorded. Through the
      analysis of ECG signal which is measured with wearable patch-style HAMS, the
      parameter highly related with mental stress were extracted from frequency and
      time domain. These parameters were certified as the meaningful factor after
      correlation analysis on the results from questionnaire and stress hormone test.
      Also, it is proved that the availability of wearable patch-style heart monitoring
      system is efficient as health monitoring system in any places and occasion.

PMID- 19162896
TI  - Detection of baseline and near-fall postural stability.
AB  - It is unknown whether there are any measurable warning signs just before a
      patient falls. This study of postural position just prior to a fall involved a
      subject standing on a balance beam while wearing a gyroscope-based wireless data
      acquisition system. Results show a variation in postural position when the
      subject appeared stable. This occurred well before the subject experienced a fall
      and could not be classified as pre-fall or fall. The results show that there are
      two distinguishable levels of postural stability - baseline and near-fall.

PMID- 19162897
TI  - Performance evaluation of a Wireless Body Area sensor network for remote patient
      monitoring.
AB  - In recent years, interests in the application of Wireless Body Area Network
      (WBAN) have grown considerably. A WBAN can be used to develop a patient
      monitoring system which offers flexibility and mobility to patients. Use of a
      WBAN will also allow the flexibility of setting up a remote monitoring system via
      either the internet or an intranet. For such medical systems it is very important
      that a WBAN can collect and transmit data reliably, and in a timely manner to the
      monitoring entity. In this paper we examine the performance of an
      IEEE802.15.4/Zigbee MAC based WBAN operating in different patient monitoring
      environment. We study the performance of a remote patient monitoring system using
      an OPNET based simulation model.

PMID- 19162898
TI  - Second generation complementary and alternative medicine physiologic data
      collection and monitoring research platform.
AB  - Progress on our second generation portable system specifically designed to
      collect 24 hour ambulatory physiologic data from human subjects is reported. The
      upgraded system has more sensor flexibility and better performance and is
      smaller, lighter, and simpler to use than our previous version. The new system
      continues to support a wide variety of sensors found useful for complementary and
      alternative medicine (CAM) research and has been designed using a modular
      approach for future expansion of capabilities. The system has improved data
      storage and supports popular physiologic data formats. Support for wireless
      control and real-time data monitoring has been added which demonstrates
      capabilities to be used for physiologic feedback control. The system was designed
      specifically to support the needs of investigators studying CAM mind-body
      interventions but could be used for a variety of research needs.

PMID- 19162899
TI  - Simulated fall detection via accelerometers.
AB  - We have derived a fall detection algorithm with high sensitivity and specificity
      from a single accelerometer device worn at the hip. A small clinical trial to
      obtain accelerometer data corresponding with actual falls experienced by elderly
      patients failed to provide a statistically significant number of fall events from
      which to develop an algorithm. Consequently, the detection algorithm was based on
      analysis of acceleration data containing 201 simulated falls. Although simulated,
      falls were modelled on video data of actual falls recorded in an elderly
      population. Nineteen different fall types were represented in the simulated data
      set which is advancement on previous simulation studies.

PMID- 19162900
TI  - Getting rid of the wires and connectors in physiological monitoring.
AB  - One of the main limitations towards an easy-touse, comfortable, and reliable
      product for physiological monitoring comes from wires and associated connectors.
      Wireless solutions for data transmission are more and more common in every
      domain, but for biopotential and impedance measurements, at least one galvanic
      line will always be needed. This paper describes a new technology that can make
      possible the measurement of biopotentials and body impedances with high quality
      standard using only one wire. As this wire requires neither shield nor isolation,
      one can imagine a conductive garment that simply connects several sensors
      distributed over the body. From the user point of view, the product would be
      'cableless'.

PMID- 19162901
TI  - Wireless On-Body-Network breathing rate and depth measurement during activity.
AB  - This paper describes a method of detecting and analyzing breathing rate and
      approximate depth during physical activity in a Bluetooth Wireless On-Body
      Network (OBN) in the context of a Spinal Cord Injured patient. Conventional
      signal processing techniques and sensor fusion through a Linear Kalman Filter
      will be used to fuse signals from a piezoelectric breathing band and two tri-axis
      accelerometers. Results will show that the proposed method provides very accurate
      measurements of breathing rate and depth at rest and during physical activity.

PMID- 19162902
TI  - Evaluation of a tactile display around the waist for physiological monitoring
      under different clinical workload conditions.
AB  - In this study, we have assessed the usability of a tactile belt prototype for
      clinical monitoring of physiologic patient data in the operating room under low
      workload (LW) and high workload (HW) conditions. In previous investigations, we
      have evaluated tactile technology in clinical settings and demonstrated that
      anesthesiologists have enhanced situational awareness towards adverse clinical
      events when a tactile display prototype is used as a supplemental monitoring
      device. To further evaluate the effectiveness of our tactile belt prototype, we
      compared the effects of workload on the performance of anesthesiologists in terms
      of accuracy and response time in tactile alert identification. We also
      administered a post-study questionnaire to evaluate the usability of the tactile
      belt as well as users' opinions about the device. We found that the response time
      to tactile alert identification to be faster under LW than under HW, however the
      accuracy of identification was not statistically different. Participants rated
      the tactile belt prototype as comfortable to use and the tactile alert scheme as
      easy to learn. Our findings further support the feasibility and efficacy of
      vibrotactile devices for enhancing physiological monitoring of patients in
      clinical environments.

PMID- 19162903
TI  - Pervasive technology in Neonatal Intensive Care Unit: a prototype for newborns
      unobtrusive monitoring.
AB  - Pervasive computing research is introducing new perspectives in a wide range of
      applications, including healthcare domain. In this study we explore the
      possibility to realize a prototype of a system for unobtrusive recording and
      monitoring of multiple biological parameters on premature newborns hospitalized
      in the Neonatal Intensive Care Unit (NICU). It consists of three different units:
      a sensitized belt for Electrocardiogram (ECG) and chest dilatation monitoring,
      augmented with extrinsic transducers for temperature and respiratory activity
      measure, a device for signals pre-processing, sampling and transmission through
      Bluetooth(R) (BT) technology to a remote PC station and a software for data
      capture and post-processing. Preliminary results obtained by monitoring babies
      just discharged from the ward demonstrated the feasibility of the unobtrusive
      monitoring on this kind of subjects and open a new scenario for premature
      newborns monitoring and developmental cares practice in NICU.

PMID- 19162904
TI  - Quality of service support in wireless sensor networks for emergency healthcare
      services.
AB  - The reliable and efficient operation of emergency healthcare (e-emergency)
      services poses quality demands to the systems and underlying communication
      infrastructures. In this context, most existing wireless body sensor networks
      fall short in meeting these demands as they only offer an unreliable service
      delivery. e-Emergency systems must provide quality of service (QoS) support so
      that a pervasive and trustable assistance is provided to patients under health
      risk. This paper discusses the need for QoS in wireless e-health and e-emergency
      services. To demonstrate this need, some current and relevant e-health projects
      with QoS requirements are presented. The study reveals the importance of
      providing QoS support in this emerging field of application and provides a
      summary characterizing the e-health proposals herein presented.

PMID- 19162905
TI  - Comparison of conductive fabric sensor and Ag-AgCI sensor under motion artifacts.
AB  - A wearable electrocardiogram(ECG) device using conductive fabric sensor was
      compared with traditional Ag-AgCl electrode ECG device. The ECG signals were
      measured under existence of motion artifacts on variable running speed using
      treadmill to verify that wearable device can substitute traditional ECG device. A
      signal to noise ratio (SNR) and RR interval were compared between the two
      devices. The SNR of wearable device was similar or higher than that of clinical
      device and difference of RR interval was 2ms. The results show that the wearable
      ECG device using conductive fabric sensor can make similar performance with ECG
      device using Ag-AgCl electrode even under motion artifacts.

PMID- 19162906
TI  - A novel design and evaluation of wearable digital sensor for monitoring posture.
AB  - In this study, we propose a novel design of the wearable digital sensor, embedded
      within a monitoring suit for posture monitoring. Our studies are going to solve
      wearable monitoring systems' drawbacks, include non-washable, uncomfortable, and
      high power -consumption due to complex signal processing. There are two digital
      sensor designs, dome shape type and clip shape type, knitted on clothes. The
      characteristics of these two digital sensor designs are easy implementation,
      small size, low power-consumption, and comfort. Our proposed system can catch up
      and monitor postures of the real-time information from the wearing person.
      Therefore, the monitoring system embedded with the capability of detecting real
      time postures and transmission makes it highly suitable for applications of
      remote healthcare and wellness.

PMID- 19162907
TI  - A hydrostatic calibration method for the design of wearable PAT-based blood
      pressure monitoring devices.
AB  - Pulse arrival time (PAT) has been proposed for measuring blood pressure (BP)
      noninvasively and continuously. A challenge of the PAT-based BP measurement
      technique is to calibrate it individually. The objective of this study is to
      examine a previously proposed model-based calibration method utilizing
      hydrostatic pressure for BP estimation. A preliminary experiment has been
      conducted on eight subjects aged from 23 to 36. Each subject was asked to raise
      their right arms to five different heights (H). At each height, PAT and brachial
      BP were measured from the elevated arm and the resting arm respectively. The data
      recorded at each height were used to calibrate a subject-dependent coefficient b
      which was then used to estimate his/her brachial SBP before and after exercise.
      It was found that the estimation results were influenced by H and k, which is a
      constant time interval subtracted from PAT. In this study, the estimation errors
      were found to be more sensitive to H than to k for -30< or =H< or =30 cm and 40<
      or =k< or =70 ms.

PMID- 19162908
TI  - Detection of nocturnal hypoglycemic episodes (natural occurrence) in children
      with Type 1 diabetes using an optimal Bayesian neural network algorithm.
AB  - Hypoglycemia or low blood glucose is dangerous and can result in unconsciousness,
      seizures and even death. It is a common and serious side effect of insulin
      therapy in patients with diabetes. HypoMon is a non-invasive monitor that
      measures some physiological parameters continuously to provide detection of
      hypoglycemic episodes in Type 1 diabetes mellitus patients (T1DM). Based on heart
      rate and corrected QT interval of the ECG signal, we have continued to develop
      Bayesian neural network detection algorithms to recognize the presence of
      hypoglycemic episodes. From a clinical study of 16 children with T1DM, natural
      occurrence of nocturnal hypoglycemic episodes are associated with increased heart
      rates (1.033+/-0.242 vs. 1.082+/-0.298, P0.06) and increased corrected QT
      intervals (1.031+/-0.086 vs. 1.060+/-0.084, P0.001). The overall data were
      organized into a training set (8 patients) and a test set (another 8 patients)
      randomly selected. Using the optimal Bayesian neural network with 10 hidden nodes
      which was derived from the training set with the highest log evidence, the
      sensitivity (true positive) value for detection of hypoglycemia in the test set
      is 89.2%.

PMID- 19162909
TI  - ECG monitoring of a car driver using capacitively-coupled electrodes.
AB  - Many reports show that there are a lot of traffic accidents due to sleeping while
      driving. Then, demand for measuring electrocardiogram (ECG) to estimate
      drowsiness of drivers has increased to prevent these accidents. In this paper, we
      propose an ECG monitoring system of a car driver using capacitively-coupled
      electrode. This capacitively-coupled electrode on which an operational amplifier
      (OP amp) was mounted was embedded inside a seat for measuring ECG signal. A
      ground electrode was placed on a steering wheel, i.e. ECG signal was amplified by
      a single-ended amplifier. Subjects wore their regular suits and pants made of
      wool, and ECG was obtained during driving at low speed on a rough road with one
      corner. Results show that our system can be used to obtain ECG while driving at
      low speed except some motion artifacts caused by the steering operation, road
      surface, braking, and accelerating.

PMID- 19162910
TI  - A performance comparison of accelerometry-based step detection algorithms on a
      large, non-laboratory sample of healthy and mobility-impaired persons.
AB  - Accelerometers are frequently used for activity assessment and as reference
      devices for counting steps. Their performance on healthy subjects' data is good,
      but there are doubts as to their applicability on elderly and mobility-impaired
      subjects. Furthermore, only few step detection algorithms have been published so
      far, and their performance has not been evaluated on a large, non-laboratory
      sample. The aim of this paper is to compare the performance of four freely
      accessible accelerometry-based step detection algorithms in a non-laboratory
      setting. Two samples of healthy persons (n=140) and mobility-impaired, geriatric
      in-patients (n=10) wore a single triaxial accelerometer on a waist-belt during
      unconstrained walking. The relative error rate of the four algorithms on the two
      samples was compared with reference video recordings. All four algorithms show a
      fairly poor performance on healthy subjects' (8.4-30.8% relative error rate) and
      especially geriatric patients' data (28.1-62.1%). Among the tested ones, a simple
      autocorrelation algorithm works best on both data sets together. More complex
      algorithms might work better, and more research is needed to evaluate the
      accuracy of step detection methods on mobility-impaired subjects.

PMID- 19162911
TI  - A new visual feed-back modality for the reduction of artifacts in mu-rhythm based
      brain-computer interfaces.
AB  - A common problem in EEG recording sessions is that results can be heavily
      contaminated by artifacts. One of the main reasons is that eyes movements
      generate a noise signal that superimpose to the data. In some BCI protocols the
      user has generally to control the movement of a cursor on a PC screen by self
      regulating his/her mu-rhythm. In general this requires the user to move the eyes
      to follow the same cursor, thus intrinsically generating a huge amount of noise.
      To overcome this problem a new feedback modality has been developed, which is
      able to dramatically reduce the artifacts as it does not require subjects to move
      their eyes.

PMID- 19162912
TI  - Cuffless and non-invasive Systolic Blood Pressure estimation for aged class by
      using a Photoplethysmograph.
AB  - This study provides cuffless and non-invasive technique of Systolic Blood
      Pressure (SBP) estimation by using only a Photoplethysmography (PPG) sensor. As
      people get older, cardiovascular peculiarities are changing more and more, so
      this study focuses on the presumption of SBP in old age. Ages 60 and over were
      defined as old age and grouped into an aged class in this study, ages fewer than
      60 were grouped into a young-middle class. The measured data in this experiment
      were both Capacity Pulse Wave (PW) and SBP. PW was obtained by the PPG and SBP
      was obtained by the commercial Blood Pressure (BP) meter with a cuff. Then the
      regression equation of SBP was calculated from individual information and
      features of PW. 96 healthy volunteers participated in the BP and PW measurement
      experiment. This result implied that patients' cardiovascular peculiarities
      change according to aging and vary among difference individuals. Furthermore, the
      data of old age were classified into four classes through a boundary values that
      depend on b and d of Acceleration Pulse Wave (APW). As regards the result of the
      aged class, the measured SBP was significantly correlated with the presumed SBP
      (r=0.89, SD=8.2mmHg) and the SD was 5.5 mmHg better than the SD of non-classified
      data. In conclusion, it is quite important for SBP estimation to divide data into
      several classes by age. Besides, the classification by using the parameters with
      the features of APW as individual cardiovascular peculiarities is a hopeful
      technique for the aged class. Therefore, the proposed techniques are quite
      promising and useful for the feature studies on cuffless and continuous BP
      monitoring.

PMID- 19162913
TI  - Modeling of electromagnetic environment of transmission lines for studying effect
      of ELF-EMF.
AB  - By combining two groups of three-phase power lines, a modeling that can induce
      power frequency electromagnetic fields has been presented. Charge simulation
      method and Biot-Savart law have respectively been adopted to compute the three
      dimensional electric and magnetic fields in exposed environment of the modeling.
      Simulations indicate that the intensity of electric field can reach up to 5 kil
      volt per meter (kV/m) at ground level, and the magnetic flux density can amount
      to 15 microtesla (microT). A comparison has been conducted between the
      environments that mice and human bodies are exposed to. The paper concluded that
      the modeling can be utilized in studying white mice simultaneous exposure to
      power frequency electric field and magnetic field emitted from transmission
      lines.

PMID- 19162914
TI  - Two-way ANOVA to identify impacts of multiple interactive behavioral factors on
      the neuronal population dependency during the reaching motion.
AB  - Brain neural activities interact with behaviors. The contribution of this paper
      is that we investigate the significance of the impacts of multiple behavioral
      factors: target direction (left or right) and obstacle (presence or absence), and
      their interaction on the dependency among a neuronal ensemble in the dorsal
      premotor (PMd) area of a monkey during a reaching motion. We first use
      bootstrapping to extract multiple resamples from successful trials. Then we use
      redundancy to measure dependency in each resample. We use ANOVA to investigate
      the significance of the impacts of these two behavioral factors and their
      interaction on the redundancy. The ANOVA shows that these two behavioral factors
      and their interaction have significant impacts on the single feature of neural
      activity. The same significance of impacts is identified in another neuronal
      ensemble assessed in another experimental session. Its biological explanation is
      given.

PMID- 19162915
TI  - Robust spots finding in microarray images with distortions.
AB  - Microarray images, which allow the analysis of hybridization expressions of
      genes, have been one of the most widely used high-throughput technologies with
      many different applications. Accurate and automatic microarray image analysis is
      very important since researchers trust the information provided in these
      experiments and construct conclusions based on the results produced by the
      software responsible in analyzing the hybridized arrays. Every microarray image
      contains thousands of spots, so how to do the spots finding in microarray images
      accurately and automatically is very meaningful. There are always some problems,
      such as rotation and distortion, in a microarray image caused by mechanical
      errors and/or optical errors in the system. All these problems will hinder
      "doi"ng analysis automatically. Early research has worked out several algorithms
      to deal with the rotation problem, but those algorithms can not handle microarray
      images with distortions. In this paper, we propose a robust spots finding method
      to deal with both rotation and/or distortion in microarray images. The proposed
      method provides automatic gridding and can handle a microarray image with
      different type of rotation (global or sub-array rotation) and optical
      distortions.

PMID- 19162916
TI  - A massively parallel implementation of gillespie algorithm on FPGAs.
AB  - This paper targets the acceleration of complex stochastic simulations of
      biochemical systems by a dedicated hardware architecture on configurable devices
      (FPGA). Existing approaches are discussed and compared with the proposed one, and
      experimental data is introduced to support the feasibility of the system.
      Retargetable hardware description can be automatically generated for any suitable
      simulation problem, and preliminary results show very high performance - 100
      million time steps per second for large models (1000 reactions).

PMID- 19162917
TI  - Detecting remote homologues using scoring matrices calculated from the estimation
      of amino acid substitution rates of beta-barrel membrane proteins.
AB  - Beta-barrel membrane proteins (MP) are found in Gram-negative bacteria,
      mitochondria and chloroplasts. They play important roles in metabolism of
      bacteria, where they are involved in transport of solutes in and out of the cell.
      Beta-barrel proteins may also act as proteases, lipases and may be important for
      cell-cell adhesion. Currently, there are about 30 non-redundant solved structures
      of beta-barrels. Although the number of b-barrel folds is fairly small, it is
      possible to expand the amount of available structural information by homology
      modeling using existing structures as templates. The scope of structure
      prediction may be widened by finding remote homologues of the existing
      structures. To improve the sensitivity of the database searches and the quality
      of sequence alignments, we first study evolutionary history of transmembrane
      segments of 7 beta-barrel membrane proteins by estimating substitution rates with
      a Bayesian Monte Carlo approach. Next, we calculate amino acid substitution
      matrices, beta-barrel Transmembrane scoring Matrices (bbTM), specifically tuned
      for TM regions, which can be used to detect remote homologues. We then test bbTM
      matrices by comparing their performance with membrane-protein derived scoring
      matrices PHAT and SLIM. Our results demonstrate that bbTM matrices have higher
      selectivity towards transmembrane beta-barrel proteins and may be used with
      higher confidence in database searches for remote homologues of this class of
      proteins.

PMID- 19162918
TI  - Discrimination of single and multiple human transmembrane proteins using kurtosis
      and morphological analysis.
AB  - The identification of transmembrane segments in protein sequences is an important
      issue in the field of bioinformatics. In this study a method is proposed for the
      discrimination between proteins with single and multiple transmembrane segments,
      combining chemical and statistical features of the proteins with higher-order
      statistics and morphological analysis for protein categorisation. The method was
      tested on human proteins, extracted from public available databases and the
      results have shown an efficiency of the proposed algorithm to correctly classify
      the sequences under study into two classes, for a wide range of transmembrane
      segment lengths. This paves the way for a more efficient analysis of
      transmembrane proteins taking into account the individual features and patterns
      occurring within proteins with single and multiple transmembrane segments.

PMID- 19162919
TI  - A two-stage neural network based technique for protein secondary structure
      prediction.
AB  - Protein secondary structure prediction is one of the most important research
      areas in bioinformatics. In this paper, we propose a two-stage protein secondary
      structure prediction technique, implemented using neural network models. The
      first neural network stage of the proposed technique associates the input protein
      sequence to a bin containing its corresponding homologues. The second stage
      predicts the secondary structure of the input sequence utilizing a neural
      prediction model specific to the bin obtained from stage one. The strategy of
      binning allows for simplified and accurate neural models. This technique is
      implemented on the RS126 dataset and its prediction accuracy is compared with
      that of the standard PHD approach.

PMID- 19162920
TI  - A real valued Genetic Algorithm for generating native like structure of small
      globular protein.
AB  - Predicting the 3D native conformation of a protein given the amino acid sequence
      is known as protein structure prediction (PSP) problem and is one of the greatest
      challenges of computational biology. The current work uses a real valued Genetic
      Algorithm (GA), a powerful variate of GA to simulate the PSP problem. This
      algorithm consists of basic evolutionary operators and a fitness vector. The
      fitness vector is designed by combining a set of knowledge based biophysical
      filters viz. persistence length, radius of gyration, packing fraction,
      hydrophobicity ratio and irregularity index of phi and psi. This vector converts
      all these biophysical measures into a real value by using specific weights or
      factors. The algorithm has been validated on six known globular proteins, with
      their length varying from 17-61 residues and total number of helices and strands
      in the range of 2-4. For all the test protein the algorithm converges rapidly and
      the converged structure shows a backbone RMSD (root mean square deviation) of 3
      6A as compared to the native structure.

PMID- 19162921
TI  - A UML model for the description of different brain-computer interface systems.
AB  - BCI research lacks a universal descriptive language among labs and a unique
      standard model for the description of BCI systems. This results in a serious
      problem in comparing performances of different BCI processes and in unifying
      tools and resources. In such a view we implemented a Unified Modeling Language
      (UML) model for the description virtually of any BCI protocol and we demonstrated
      that it can be successfully applied to the most common ones such as P300, mu
      rhythms, SCP, SSVEP, fMRI. Finally we illustrated the advantages in utilizing a
      standard terminology for BCIs and how the same basic structure can be
      successfully adopted for the implementation of new systems.

PMID- 19162922
TI  - An efficient algorithm for local sequence alignment.
AB  - DNA pairwise sequence alignment has been a subject of great interest in the past
      and still evokes large interest. Recent algorithms have either been slow and
      sensitive or fast and less sensitive. Here, we present a new algorithm which is
      fast and at the same time relatively sensitive. To increase the speed, we first
      build a suffix tree for both sequences and the alignment is triggered by the
      maximum matching substring. The algorithm employs mismatch seeds to increase both
      sensitivity and speed in the later stages. We tested our algorithm on randomly
      generated sequences of length up to 500 thousand and used Rosetta dataset to test
      the sensitivity of the algorithm.

PMID- 19162923
TI  - The impact of wall shear stress and pressure drop on the stability of the
      atherosclerotic plaque.
AB  - Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries
      often leads to stroke and heart attack respectively. The mechanism of blood flow
      and plaque rupture in stenotic arteries is still not fully understood. A three
      dimensional rigid wall model was solved under steady state conditions and
      unsteady conditions by assuming a time-varying inlet velocity profile to
      investigate the relative importance of axial forces and pressure drops in
      arteries with asymmetric stenosis. Flow-structure interactions were investigated
      for the same geometry and the results were compared with those retrieved with the
      corresponding 2D cross-section structural models. The Navier-Stokes equations
      were used as the governing equations for the fluid. The tube wall was assumed
      hyperelastic, homogeneous, isotropic and incompressible. The analysis showed that
      the three dimensional behavior of velocity, pressure and wall shear stress is in
      general very different from that predicted by cross-section models. Pressure drop
      across the stenosis was found to be much higher than shear stress. Therefore,
      pressure may be the more important mechanical trigger for plaque rupture other
      than shear stress, although shear stress is closely related to plaque formation
      and progression.

PMID- 19162924
TI  - In vivo velocity and flow errors quantification by phase-contrast magnetic
      resonance imaging.
AB  - Magnetic resonance imaging is a very efficient tool for assessing velocity and
      flow in the cardiovascular system under normal and pathological conditions.
      However, this technique still has some limitations that produce different type of
      errors. In this study, velocities and flow were measured in vivo using phase
      contrast method to determine the optimal number of phases allowing the
      minimization of the errors. The effect of velocity encoding upsampling was also
      investigated. The results showed that a number of phases between 16-24 is a good
      compromise to accurately estimate both ejection and regurgitant flows.
      Furthermore, a time shift effect caused by velocity encoding upsampling was found
      and a corrective linear model was proposed. These considerations may reduce flow
      and velocity measurement errors in normal and pathological conditions.

PMID- 19162925
TI  - Reservoir-wave separation and wave intensity analysis applied to carotid
      arteries: a hybrid 1D model to understand haemodynamics.
AB  - Pressure waveforms measured at different locations in the cardiovascular system
      present a very similar diastolic decay. Previous work has shown the
      cardiovascular system can be modelled as a Windkessel and wave system. This
      concept has been extended to any arbitrary location in the cardiovascular system.
      We suggest that it is possible to calculate a time-varying reservoir pressure
      P(t) and a distance- and time-varying wave pressure p(x, t) by fitting an
      exponential function to the diastolic decay of the measured pressure P; defining
      that the measured pressure P(x, t) = P(t)+p(x, t). Velocity waveforms U can also
      be separated into its reservoir, U , and wave, u,components as U(x, t) = U (x, t)
      + u(x, t).In this study we explore the implications of applying are servoir-wave
      separation and wave intensity analysis techniques to understand the haemodynamics
      of in-vivo, noninvasive measurements of P and U in the carotid arteries of normal
      human subjects. Wave intensity analysis reveals a particular wave pattern where
      reflections can be estimated easily, but foremost, it shows that reflections are
      a lot smaller than previously thought.We suggest through the use of this model
      that the heart is the main wave generator of the cardiovascular system. The
      arterial system instead of impeding the flow, it stores it and distributes it
      throughout the arteries towards the tissue during diastole. There are some wave
      reflections, mainly during systole,that contribute to the changes in the pressure
      and velocity waveforms, however, they are small and are more evident as the
      measurements get further away from the ascending aorta.The application of wave
      intensity analysis to non-invasively measured data can provide a good insight on
      the physiology and the local and global properties of the cardiovascular system
      in health and disease in the clinical setting. This study shows preliminary
      results and the potential of the technique for analysing non-invasive measures,
      and could be particularly useful to understand and quantify the effects of
      therapeutic drugs in the cardiovascular system.

PMID- 19162926
TI  - Estimation of the aortic pressure waveform from a peripheral artery pressure
      waveform via an adaptive transfer function.
AB  - We developed a new technique to estimate the aortic pressure (AP) waveform from a
      single peripheral artery pressure (PAP) waveform. The technique 1) employs a
      parallel tube model of the arterial tree to establish a transfer function
      relating PAP to AP with unknown parameters; 2) estimates the parameters from the
      measured PAP waveform, along with a single non-invasive measurement of the wave
      transmission delay from the aorta to the peripheral artery measurement site, by
      exploiting the fact that aortic flow is zero during diastole; and 3) applies the
      transfer function to the PAP waveform to predict the unmeasured AP waveform. In
      this way, in contrast to the conventional generalized transfer function paradigm,
      the transfer function is able to adapt to the inter-subject and temporal
      variability of the arterial tree. We applied this adaptive transfer function
      technique to PAP waveforms measured from five dogs instrumented with reference AP
      catheters during various hemodynamic interventions. Our results showed that the
      technique was able to reliably estimate the AP waveform with an overall error of
      4.2 mmHg. For comparison, the corresponding errors of two previously proposed
      generalized transfer functions trained on a subset of the same canine data were,
      on average, 19% larger.

PMID- 19162927
TI  - Physiological role of nitric oxide in oxygen consumption by arteriolar wall.
AB  - To study the role of nitric oxide (NO) in regulating oxygen consumption by vessel
      walls, the oxygen consumption rate of arteriolar walls in rat cremaster muscle
      was measured in vivo during flow-induced vasodilation and after inhibiting NO
      synthesis. The oxygen consumption rate of arteriolar walls was calculated based
      on the intra- and peri-vascular oxygen tension (PO(2)) values measured by
      phosphorescence quenching laser microscopy. The peri-vascular PO(2) value of the
      arterioles during vasodilation was significantly higher than under control
      conditions, although the intravascular PO(2) values under both conditions were
      approximately the same. On the other hand, inhibition of NO synthesis caused a
      significant decrease in both the intra- and peri-vascular PO(2) values of the
      arterioles. The inhibition of NO synthesis increased the oxygen consumption rate
      of the vessel walls by 42%, whereas enhancement of flow-induced NO release
      decreased it by 34%. These results suggest that NO plays an important role not
      only as a regulator of peripheral vascular tone, but also as a modulator of
      tissue oxygen consumption by reducing oxygen consumption by vessel walls.

PMID- 19162928
TI  - Trileaflet valve hydrodynamic resistance assessment.
AB  - Valve hydrodynamic performance is usually assessed by effective orifice area,
      transvalvular resistance, regurgitation and blood damage effect. Some studies
      suggest effects in effective orifice area due to cardiovascular resistance,
      compliance and angle position of the valve. We suppose that silicone rubber
      valves under study have a good performance under different cardiovascular
      resistance conditions. Two in vitro experiments were made to test this hypothesis
      under constant and pulsatile flow rate. Transvalvular gradient pressure,
      transvalvular resistance, Gorling effective orifice area, effective orifice area
      in the ascending aorta and Reynolds numbers were estimated in both flow rates.
      Results suggest that cardiovascular resistance has no significant effect for this
      kind of valves, however resistance effect is observed in pumping pressure. Small
      transvalvular resistance and transvalvular pressure gradients were found. Gorlin
      effective orifice areas greater than 0.3 cm(2) have not viscosity effect. P-value
      0.001 was found between Gorlin effective orifice area under constant and
      pulsatile flow rate.

PMID- 19162929
TI  - Aortic impedance in Little mice.
AB  - The Little dwarf mouse lives 30% longer than its age-matched wild-type (WT)
      mouse. We determined aortic input impedance in 21 (8 Little, 13 WT) 4 month-old
      mice. Modulus of impedance was calculated from the Fourier transformed aortic
      pressure (P) and average luminal flow velocity (V(avg)) as |Z(i)| = |P|/|V(avg)|.
      Characteristic impedance was estimated by averaging the 2(nd)-10(th) harmonic of
      the impedance moduli. We found the impedance modulus |Z(i)| to be similar in the
      2 groups (WT vs. Little; mean+/-SE) - peripheral resistance (10597+/-654 vs.
      12932+/-1433 dyne-s/cm(3)), modulus at first harmonic (Z(1): 740+/-56 vs. 902+/
      105 dyne-s/cm(3)), and characteristic impedance (Z(c): 441+/-34 vs. 470+/-60 dyne
      s/cm(3)). Also, mean aortic velocity (20.1+/-1.1 vs. 16.5+/-1.8 cm/s) and mean
      aortic blood pressure (81.1+/-3.9 vs. 75.9+/-5.9 mmHg) were similar between the
      two groups. Impedance at low frequencies was slightly higher in the dwarf mice
      which may be due to the diminished systolic function as indicated by significant
      reduction in peak aortic velocity (84.0+/-3.2 vs. 70.1+/-1.2 cm/s, p<<0.01).
      Although modestly higher, the overall impedance in Little mice was similar to
      that in WT mice. This indicates that left ventricular (LV) afterload may not
      significantly be altered in Little mice.

PMID- 19162930
TI  - Investigation of mouse conductance catheter position deviation effects on volume
      measurements by finite element models.
AB  - The conductance catheter system is used to measure the instantaneous ventricular
      conductance, and real-time ventricular volumes is then determined by converting
      the measured conductance to volume. In fact, two different conductance-to-volume
      conversion equations for conductance catheters have been proposed, the Baan's
      classic equation and Wei's nonlinear equation. The accuracy of this volume
      estimation method is limited by several factors, such as the deviation of the
      catheter position inside the ventricle. The effects of the mouse catheter radial
      and longitudinal position deviations on the measured conductance are investigated
      with finite element models. Moreover, the capacities of the two conversion
      equations to calibrate the error induced by the catheter position variation are
      evaluated and compared. According to the simulation results, the error-calibrated
      capacity of the nonlinear conversion equation is better.

PMID- 19162931
TI  - Measurement of stenotic carotid arterial compliance with MRI.
AB  - Arterial compliance has been shown to correlate well with overall cardiovascular
      outcome and it may also be a potential risk factor for the development of
      atheromatous disease. This study assesses the utility of 2-D phase contrast
      Magnetic Resonance (MR) imaging with intra-sequence blood pressure measurement to
      determine carotid compliance and distensibility. 20 patients underwent 2-D phase
      contrast MR imaging and also ultrasound-based wall tracking measurements. Values
      for carotid compliance and distensibility were derived from the two different
      modalities and compared. Linear regression analysis was utilised to determine the
      extent of correlation between MR and ultrasound derived parameters. In those
      variables that could be directly compared, an agreement analysis was undertaken.
      MR measures of compliance showed a good correlation with measures based on
      ultrasound wall-tracking (r=0.61, 95% CI 0.34 to 0.81 p=0.0003). Vessels that had
      undergone carotid endarterectomy previously were significantly less compliant
      than either diseased or normal contralateral vessels (p=0.04). Agreement studies
      showed a relatively poor intra-class correlation coefficient (ICC) between
      diameter-based measures of compliance through either MR or ultrasound (ICC=0.14).
      MRI based assessment of local carotid compliance appears to be both robust and
      technically feasible in most subjects. Measures of compliance correlate well with
      ultrasound-based values and correlate best when cross-sectional area change is
      used rather than derived diameter changes. If validated by further larger
      studies, 2-D phase contrast imaging with intra-sequence blood pressure monitoring
      and off-line radial artery tonometry may provide a useful tool in further
      assessment of patients with carotid atheroma.

PMID- 19162932
TI  - A nonlinear lumped parameters model to analyze the dynamics of venous reflux.
AB  - The aim of this work is to formulate a lumped parameters model of the venous tree
      of the lower limbs in order to study the effects and the possible clinical
      treatments for Chronic Venous Insufficiency (CVI). CVI is a pathology
      characterized by an important socio-economic impact due to its relevant
      prevalence, the costs for its diagnosis and treatment being more frequently
      widespread among the working population. The planning of haemodynamic surgical
      operations is critical to treat a pathological pattern of venous blood flow; such
      planning, in turn, depends on the right analysis of the possible consequences of
      flow modification. To this regard, the blood flow correction allows to solve the
      most important venous pathologies, in order to guarantee the restoration of
      normal blood flow by means of proper modifications of the venous tree. The
      developed model preserves the geometry of the venous network and considers some
      non linear resistive and capacitive effects. In fact, the study of the
      variability of some parameters (i.e. vessel radius) is very important to allow a
      correct diagnosis of vascular diseases. This variability causes a non linear
      behaviour of resistance and compliance effects. With the aid of the developed
      model we evaluate the time profile of blood velocity, flow and pressure in the
      entire venous network, both in physiological and pathological cases. The obtained
      results are discussed in comparison with available experimental data.

PMID- 19162933
TI  - A haemodynamic study of the physiological mechanisms of the venous pump in the
      healthy human foot.
AB  - Presented is a physiological study of the plantar venous plexus in the context of
      venous return. It is accepted that the plantar venous plexus acts as a peripheral
      venous pump, capable of emptying blood from the foot into the posterior tibial
      veins. Controversy still exists, however, over the precise physiological
      mechanism which is responsible for completely emptying the deep plantar veins of
      the foot. This study was designed to investigate whether weight bearing or
      muscular contraction was the dominant mechanism involved. This was achieved by
      comparing blood flow measurements taken from the posterior tibial and popliteal
      veins while performing specific foot exercises. Measurements were taken using
      Doppler ultrasound. Neuromuscular electrical stimulation was also used to study
      the blood flow obtained by artificially inducing contraction of the plantar
      venous plexus.

PMID- 19162934
TI  - Variations in non-invasive radial artery pulse waveform at different measuring
      positions.
AB  - Noninvasive radial artery pulse wave has been widely not only for the pulse wave
      analysis (PWA) itself but also for assessment of arterial stiffness with
      estimated aortic pulse wave from peripheral pulse wave. In this study, we tested
      the differences between the extracted parameters, including AIx, from radial
      artery pulse waves measured at three different positions preliminarily. A 30
      years old female involved in this experiment and this subject has no evidence
      about cardiovascular diseases. Radial pulse waves were recorded at three
      different positions on left lower arm ten times for each position. These
      positions are widely used in pulse diagnosis of traditional medicine.As results
      of repeated measures ANOVA analysis, 9 parameters were found which had
      significantly differences in between measuring positions (P<0.05). These
      parameters wereP_AIx, PP_Amp, A_T1, A_Tr, AIx, AIx_@HR75, ESP, MP_Sysand MP_Dia.
      And, by Spearman correlation test at P2, it was observed that P_AIx (r =0.894),
      PP_Amp (r=-0.765),AIx_@HR75 (r=0.929), ESP (r=0.893) and MP_Dia (r=0.792)were
      highly correlated with AIx. Elaborately, the correlation coefficients between
      each parameter were high in similar degrees (r>0.70).Further studies on what make
      differences in these parameters between measuring positions are need. And,
      ultimately, we need to determine the best measuring process, including measuring
      position, hold-down pressure, signal quality validation and so on,so to achieve
      the optimal waveform which represents subject's health condition for both western
      medicine and traditional medicine.

PMID- 19162935
TI  - Fluid dynamics studies of cardiovascular medical devices and blood damage
      prediction.
AB  - The implantation of cardiovascular devices such as prosthetic heart valves, even
      though very common in the clinical domain, is still not free from complications.
      Thromboembolic events and hemolysis are the major clinical problems that can
      occur, upon implantation. In this paper, we analyze the role of the particular
      fluid dynamics associated to such devices, in relation to the clinical outcome. A
      major issue, still debated, is the way to correlate the experimental findings
      with blood damage. The availability of advanced techniques such as LDA or PIV is
      necessary to evaluate the hemodynamical performance of a given implantable device
      at the local level and to draw reliable conclusions about potentially adverse
      clinical effects.

PMID- 19162936
TI  - Continuous monitoring of coordinated cardiovascular responses.
AB  - The continuous separate monitoring of cardiac and vascular functions provide
      important insights on cardiovascular regulation. In the last years several
      attempts have failed at demonstrating the feasibility of using Pulse Wave
      Velocity as a surrogate indicator of arterial blood pressure. Upon the hypothesis
      that the cause of PWV unreliability is vasomotor activity, in this paper we
      develop an extended model of lumped arterial tree that copes with changes in
      vessels diameter. The benefit of this approach is twofold: on the one hand one
      might correct the effects of vasomotor activity on the estimation of arterial
      blood pressure on the basis of PWV, and on the other hand one obtains continuous
      non-invasive estimations of Cardiac Output and Total Peripheral Resistance.

PMID- 19162937
TI  - Wireless blood velocity spectra measurement system for healthcare evaluation:
      reference data.
AB  - The aim of the present study was to determine the blood velocity and its indices
      in common carotid artery (CCA) as reference value for clinical and healthcare
      application using the constructed portable wireless Doppler blood flow
      velocimeter system. Evaluation of CCA blood velocity waveforms was performed in
      202 healthy volunteers in the age range of 20 to 69 years. Multivariate analysis
      was used to determine the relationship between the fixed factor and the outcome
      hemodynamic variables after adjustment for the related covariates. Results show a
      general age-related decrease in flow velocities and change in the velocity
      waveform. There is also a gender difference in velocity indices, except for peak
      systolic blood velocity. Gender difference is also found in systolic and pulse
      blood pressures. The findings suggest that waveform indices provide a more
      reliable evaluation of effects of aging and gender on CCA flow. In conclusion,
      normal CCA blood velocity parameters are determined in a total of 202 healthy
      volunteers between the third and seventh age decade after adjustment for gender
      and exercise effects. Findings may contribute to improved means of healthcare
      monitoring and clinical evaluation.

PMID- 19162938
TI  - Two-dimensional location and direction estimating method.
AB  - In this paper, a method of estimating both the position and the rotation angle of
      an object on a measurement stage was proposed. The system utilizes the radio
      communication technology and the directivity of an antenna. As a prototype
      system, a measurement stage (a circle 240mm in diameter) with 36 antennas that
      placed in each 10 degrees was developed. Two transmitter antennas are settled in
      a right angle on the stage as the target object, and the position and the
      rotation angle is estimated by measuring efficiency of the radio communication of
      each 36 antennas. The experimental result revealed that even when the estimated
      location is not so accurate (about a 30 mm error), the rotation angle is
      accurately estimated (about 2.33 degree error on average). The result suggests
      that the proposed method will be useful for estimating the location and the
      direction of an object.

PMID- 19162939
TI  - Wheelchair type biomedical system with event-recorder function.
AB  - The present study is about a biometric system for a wheelchair, which can measure
      both bio-signal (ECG-Electrocardiogram, BCG-Ballistocardiogram) and kinetic
      signal (acceleration) simultaneously and send the data to a remote medical
      server. The equipment was developed with the object of building a system that
      measures the bio-signal and kinetic signal of a subject who is moving or at rest
      on a wheelchair and transmits the measured signals to a remote server through a
      CDMA (Code Division Multiple Access) network. The equipment is composed of body
      area network and remote medical server. The body area network was designed to
      obtain bio-signal and kinetic signal simultaneously and, on the occurrence of an
      event, to transmit data to a remote medical server through a CDMA network. The
      remote medical server was designed to display event data transmitted from the
      body area network in real time. The performance of the developed system was
      evaluated through two experiments. First, we measured battery life on the
      occurrence of events, and second, we tested whether biometric data are
      transmitted accurately to the remote server on the occurrence of an event. In the
      first experiment using the developed equipment, events were triggered 16 times
      and the battery worked stably for around 29 hours. In the second experiment, when
      an event took place, the corresponding data were transmitted accurately to the
      remote medical server through a CDMA network. This system is expected to be
      usable for the healthcare of those moving on a wheelchair and applicable to a
      mobile healthcare system.

PMID- 19162940
TI  - Detecting patient's emergency--a minimum-computation procedure for pervasive
      cardiac monitoring.
AB  - Searching for the economy and opportunities for applications of human experience
      yielded a development of a request-driven ECG interpretation method. It assumed
      the processing of the acquired ECG is triggered by the data validity period
      expiry or by the emergency detector continuously supervising basic parameters of
      the signal. This paper focus on the correct choice of the emergency detector
      procedure covering a wide range of diseases but not requiring much computational
      power in the patient-side wearable system. After the investigation of numerical
      complexity of the initial stages of ECG processing and representation of most
      common diseases in basic cardiac parameters, we propose a short-term rhythm index
      as an emergency indicator. The computation is simple enough to be performed in a
      limited-resources environment (e.g. cell phone) without considerably influencing
      its autonomy time.

PMID- 19162941
TI  - Distance correction system for localization based on linear regression and
      smoothing in ambient intelligence display.
AB  - This paper suggests the method of correcting distance between an ambient
      intelligence display and a user based on linear regression and smoothing method,
      by which distance information of a user who approaches to the display can he
      accurately output even in an unanticipated condition using a passive infrared
      VIR) sensor and an ultrasonic device. The developed system consists of an ambient
      intelligence display and an ultrasonic transmitter, and a sensor gateway. Each
      module communicates with each other through RF (Radio frequency) communication.
      The ambient intelligence display includes an ultrasonic receiver and a PIR sensor
      for motion detection. In particular, this system selects and processes algorithms
      such as smoothing or linear regression for current input data processing
      dynamically through judgment process that is determined using the previous
      reliable data stored in a queue. In addition, we implemented GUI software with
      JAVA for real time location tracking and an ambient intelligence display.

PMID- 19162942
TI  - A data process and wavelet analysis method used for monitoring daily
      physiological attributes.
AB  - An analytical technique to evaluate human physiological states is developed for
      real-life implementation, achieving stable acquisition of data during normal
      human activity, even with the presence of several constraints and interruptions.
      Accurately measuring physiological characteristics for extended durations with
      minimal physical intrusiveness is desirable, something that can be accomplished
      by using the ubiquitous cellular phone already being used in daily life. Wavelet
      analysis and its data processing techniques for physiological data are proposed
      and examined. The data recovery and denoising methodologies are presented to make
      sense of human body attributes from incomplete data sets extracted when measuring
      normal daily life. Using the proposed techniques, the continuous measuring of
      both heart rate and body temperature can clearly expose changes in daily
      physiological patterns. The aim of developing this method is to identify subtle
      changes in human body response with limited instrumentation and calculation, by
      monitoring for long durations even when subjected to severe noise and data set
      interruptions.

PMID- 19162943
TI  - Performance evaluation of biosignal measurement at the wheelchair system.
AB  - The purpose of this study is to measure both ECG and BCG(Ballistocariograph)
      signal of a subject on moving or resting wheelchair and detect the heart rate and
      respiratory rate and transmit an event message to remote server on emergent
      situation. To acquire ECG and BCG data, amplifier circuits were composed to be
      suitable for their characteristics. 3-axial accelerometer was built in the
      developed device to measure the mechanical noise that can be generated on moving
      wheelchair.The output signals were converted to digital data and stored in bio
      signal archiving media(SD card). CDMA module was used to transmit the event data
      on ECG electrode detachment and the received data was monitored by the developed
      C# application program. 8 volunteers participated in the experiment to evaluate
      the validity of the developed device. When the event occurs in each subject, 48
      Kbyte data, stored for 32 seconds from that point, was transmitted to remote
      server through CDMA cellular phone network correctly. The received data of ECG ,
      BCG, and 3-axial acceleration could be archived in server and the heart rate and
      respiratory rate could be measured and analyzed. The correlation coefficients of
      respiratory rate in resting and moving with the real value were 0.9636 and
      0.9237, respectively. The correlation coefficient ofR-R intervals between the
      developed and reference device was 0.999.In conclusion, the developed device in
      this study could acquire the ECG and BCG data of subjects on wheelchair
      simultaneously and measure their heart rate and respiratory rate. In addition,
      event data was verified to be transmitted to remote server without any errors.

PMID- 19162944
TI  - Hospital automation system RFID-based: technology embedded in smart devices
      (cards, tags and bracelets).
AB  - RFID is a technology being adopted in many business fields, especially in the
      medical field. This work has the objective to present a system for automation of
      a hospital clinical analysis laboratory. This system initially uses contactless
      smart cards to store patient's data and for authentication of hospital employees
      in the system. The proposed system also uses RFID tags stuck to containers
      containing patient's collected samples for the correct identification of the
      patient who gave away the samples. This work depicts a hospital laboratory
      workflow, presents the system modeling and deals with security matters related to
      information stored in the smart cards.

PMID- 19162945
TI  - Design of RFID based the Patient Management and Tracking System in hospital.
AB  - The patient location information in managing for patient workflow will be worked
      efficiently within the hospital. We designed the Patient Management and Tracking
      System (PMTS) based on RFID with RSSI(Received Signal Strength Indication)
      method. This system is able to track the movement of patient in hospital, and
      manage the waiting-list of patients at a medical office. Therefore, we are sure
      that the PMTS will be useful for decreasing a duty of medical staff and increase
      a convenience of patients.

PMID- 19162946
TI  - Patients tracking and identifying inside hospital: a multilayer method to plan an
      RFId solution.
AB  - This paper shows a method to get a patient tracking RFId solution, basing on a
      multilayer planning architecture. This approach is thought to guarantee that the
      found technical solution is as much as possible coherent to the very initial
      idea. Project aims, functional requirements and technical constraints are defined
      in order to arrive to an active RFId solution to track and identify patients
      inside a hospital. The article also deals with economical issues and physical
      design aspects. In this work it's also defined a three phases process for patient
      tracking, that could serve as a guideline for different technical solutions to
      the same problem.

PMID- 19162947
TI  - Semantic upgrade and normalization of existing EHR extracts.
AB  - We present the mapping and data transformation capabilities of LinkEHR-Ed, a
      visual tool to construct formal definitions of medical concepts in the form of
      archetypes which can be defined on the basis on multiple electronic health record
      architecture such as ISO 13606. With LinkEHR-Ed, users can enrich archetypes with
      mapping information which captures the relationship between relational or XML
      data sources and archetype structures. This mapping information is then analyzed
      and compiled into an XQuery expression that transforms source instances into an
      XML document. The target document satisfies the constraints imposed by the
      archetype and at the same time is compliant with the underlying electronic health
      record architecture.

PMID- 19162948
TI  - Standardization of discharge reports with the ISO 13606 norm.
AB  - The International Organization for Standardization (ISO) has recently approved a
      new standard for the communication and semantic interoperability of electronic
      health record extracts. This standard is based on a dual model architecture,
      where a simple and generic reference model is defined for the representation of
      data and an archetype model is used for the representation of complex domain
      concepts of the electronic health record. By using this standard and a tool
      called LinkEHR-Ed, we have defined different types of hospital discharge reports
      in the form of archetypes and then we have normalized automatically discharge
      reports instances in a real environment following those archetype definitions.
      This work proves that it is possible to standardize legacy data automatically and
      enrich them with a semantic information layer by using archetypes as an
      integration and standardization mechanism.

PMID- 19162949
TI  - An information retrieval system for medical records & documents.
AB  - The forms of the medical records are different from one institute to another.
      Moreover, medical records are always stored in free text. Consequently, medical
      records almost can not be logically analyzed and understood by machines. In this
      paper, we have applied the information retrieval (IR) technique in the using of
      medical records. We have implemented an IR system for the users, such as doctors
      and patients, to query similar or related medical records to support diagnosis
      and treatment. Knowledge retrieval for reuse is the key idea of this system.

PMID- 19162950
TI  - On the diversity of eHealth security systems and mechanisms.
AB  - This paper examines the security requirements for eHealth (Electronic Health)
      records and the provided current and future technological solutions. This
      includes the Security and Privacy (S&P) requirements for diverse electronic
      health information, the current frameworks and standards maintaining proper
      handling (processing, storing, and transmitting) of such sensitive information
      and the related network architectures.

PMID- 19162951
TI  - A Semantic Web-based System for Managing Clinical Archetypes.
AB  - Archetypes facilitate the sharing of clinical knowledge and therefore are a basic
      tool for achieving interoperability between healthcare information systems. In
      this paper, a Semantic Web System for Managing Archetypes is presented. This
      system allows for the semantic annotation of archetypes, as well for performing
      semantic searches. The current system is capable of working with both ISO13606
      and OpenEHR archetypes.

PMID- 19162952
TI  - A method for physiological data transmission and archiving to support the service
      of critical care using DICOM and HL7.
AB  - An increasing amount of physiological monitoring data is displayed on medical
      devices around the world every day. By and large, much of this data is lost
      beyond hand written annotations. Opportunities exist to utilize this data for
      improved care of those patients within the NICU and for clinical research. The
      service oriented architecture paradigm offers a way of thinking of critical care
      through the provision of services of critical care provided by clinicians where
      patients may be located within or outside their intensive care unit. A major
      inhibitor to this becoming reality is the lack of a standard for the
      representation of physiological data as HL7, for example, does not include
      definitions for time series data. This research proposes a method to represent,
      transmit and archive physiological data using DICOM and HL7. To enable this, a
      DICOM file writer and viewer for the physiological time-series data is proposed
      to specifically enable the storage requirement for these data. This research is
      then tested within the context of Neonatal Intensive Care.

PMID- 19162953
TI  - Medical Image distribution and visualization in a hospital using CORBA.
AB  - In this work it is presented the solution adopted by the Heart Institute (InCor)
      of Sao Paulo for medical image distribution and visualization inside the
      hospital's intranet as part of the PACS system. A CORBA-based image server was
      developed to distribute DICOM images across the hospital together with the
      images' report. The solution adopted allows the decoupling of the server
      implementation and the client. This gives the advantage of reusing the same
      solution in different implementation sites. Currently, the PACS system is being
      used on two different hospitals each one with three different environments:
      development, prototype and production.

PMID- 19162954
TI  - An ontology-based telemedicine tasks management system architecture.
AB  - The recent developments in ambient intelligence and ubiquitous computing offer
      new opportunities for the design of advanced Telemedicine systems providing high
      quality services, anywhere, anytime. In this paper we present an approach for
      building an ontology-based task-driven telemedicine system. The architecture is
      composed of a task management server, a communication server and a knowledge base
      for enabling decision makings taking account of different telemedical concepts
      such as actors, resources, services and the Electronic Health Record. The final
      objective is to provide an intelligent management of the different types of
      available human, material and communication resources.

PMID- 19162955
TI  - MP-HA: multicycles protocol for hospital automation over multicast addressing.
AB  - This paper presents a Multicycles Protocol for Hospital Automation (MP-HA) that
      works over multicast addressing and uses a Master-Slave architecture. The
      protocol creates a segmented logical network based on multicast addressing
      associated to hospital beds. The objective of MP-HA is to ensure the determinism
      on network through medium access control mechanism increasing the transmission
      throughput. Thus, it creates a periodical environment making use of parallel
      cycles which is called multicycles.

PMID- 19162956
TI  - Multi-dimensional knowledge translation: enabling health informatics capacity
      audits using patient journey models.
AB  - This paper presents a multi-dimensional approach to knowledge translation,
      enabling results obtained from a survey evaluating the uptake of Information
      Technology within Neonatal Intensive Care Units to be translated into knowledge,
      in the form of health informatics capacity audits. Survey data, having multiple
      roles, patient care scenarios, levels, and hospitals, is translated using a
      structured data modeling approach, into patient journey models. The data model is
      defined such that users can develop queries to generate patient journey models
      based on a pre-defined Patient Journey Model architecture (PaJMa). PaJMa models
      are then analyzed to build capacity audits. Capacity audits offer a sophisticated
      view of health informatics usage, providing not only details of what IT solutions
      a hospital utilizes, but also answering the questions: when, how and why, by
      determining when the IT solutions are integrated into the patient journey, how
      they support the patient information flow, and why they improve the patient
      journey.

PMID- 19162957
TI  - A structured approach to requirements gathering creation using PaJMa models.
AB  - The process of preparation for request for proposals for health information
      systems typically results in missed opportunities for improvements due to the
      technical focus of traditional requirements gathering processes. The increased
      integration of health care systems between wards and external supporting
      agencies, reliance on professional practice guidelines, and needs for cultural
      sensitivities requires a specialized method for requirements gathering. We
      explore the use of a patient journey modeling approach (PaJMa) to requirements
      gathering using a case study of Whitby Mental Health Center. The improvement of
      the PaJMa models in increasing the level of detail of requirements, inclusion of
      nonfunctional requirements, and the identification of required practices,
      policies, and metrics demonstrate a superior method for requirements gathering in
      health care.

PMID- 19162958
TI  - Reference implementation model for Medical Information Systems' interoperability.
AB  - Interoperability, in the electronic environment of healthcare enterprises, is
      required for the effective communication between the various Medical Information
      Systems (MISs). However, interoperability is a large and multidimensional issue.
      Its syntactic dimension is linked with the use of existing messaging standards.
      Their proprietary and specialized implementations have led to the establishment
      of advanced middleware platforms in order to support the communication between
      heterogeneous MISs. This paper approaches syntactic interoperability from the
      standardization point of view and proposes a Reference Implementation Model
      (RImM), for the middleware platforms. RImM specifies the functional entities of
      this platform, the end-to-end services and the internal common messages format.
      It also specifies common communication profiles and interfaces that allow real
      world events and information to be visibly handled and distributed among MISs
      without any interference in their structure.

PMID- 19162959
TI  - Networking and plug-and-play of bedside medical instruments.
AB  - Medical device manufacturers continuously improve instruments with more
      capabilities at the point of care such as the bedside, operating room, intensive
      care unit, or emergency room. The instruments are in turn becoming more
      sophisticated; however, the operation of an instrument is still expected to be
      locally done by authorized medical personnel. The measurements from these
      instruments are stored using archaic methods such as a patient history record on
      a paper. The access to these records is cumbersome and not available unless the
      medical personnel is present at the point of care. Unfortunately, each medical
      instrument has its unique proprietary API (application programming interface - if
      any) to provide automated and electronic access to monitoring data. Integration
      of these APIs requires an agreement with the manufacturers towards realization of
      interoperable health care networking. As long as the interoperability of
      instruments with a network is not possible, ubiquitous access to patient status
      is limited only to manual entry based systems. Manual entry is being implemented
      to create electronic health records, HL7, and similar initiatives. However, they
      do not address a bottomup automation (i.e. from instrument and patient bed side
      up) to leverage the mature networking technologies in a health care setting. This
      paper demonstrates an attempt to realize an interoperable medical instrument
      interface for networking using MediCAN technology suite as an open standard. We
      will present the approach with a comparison study of a similar initiative led by
      ISO/IEEE 11073 standards.

PMID- 19162960
TI  - Standardization work on personalized eHealth systems.
AB  - For widespread adoption of eHealth, and to achieve eInclusion and eAccessibility,
      eHealth systems must be tailored to each individual user's needs and preferences.
      Many eHealth products and services contain adjustable parameter settings, but
      they are specific to each product and unrelated to each other. This paper
      describes ongoing work to establish standards and guidelines for personalization
      of eHealth systems, taking into account the needs of all users, both clients and
      caregivers. The standard builds on a generic 'user profile', which stores data
      about the users, their preferences and their context. This profile can then be
      used by eHealth services and devices to ensure a user experience tailored to each
      person. The work surveys relevant areas of personalization, like identity
      management, profile management etc, addressing in depth those aspects of
      personalization that are specific to eHealth: User capabilities, care provider
      roles and functions, health related information, and confidentiality measures.

PMID- 19162961
TI  - Personalized healthcare comment service for hypertension patients using mobile
      device.
AB  - Hypotension and hypertension are chronic diseases, which can be effectively
      prevented and controlled by constantly monitoring. In this study, personalized
      healthcare comment service for hypertension patients is proposed and implemented.
      We have developed algorithms of health state code generation and doctor's
      comments for patients on case-by-case basis. This prototype service shows how
      such personalized comments can manage patients with hypertension using blood
      pressure monitor and mobile device.

PMID- 19162962
TI  - Trust evaluation in health information on the World Wide Web.
AB  - The impact of health information on the web is mounting and with the Health 2.0
      revolution around the corner, online health promotion and management is becoming
      a reality. User-generated content is at the core of this revolution and brings to
      the fore the essential question of trust evaluation, a pertinent problem for
      health applications in particular. Evolving Web 2.0 health applications provide
      abundant opportunities for research. We identify these applications, discuss the
      challenges for trust assessment, characterize conceivable variables, list
      potential techniques for analysis, and provide a vision for future research.

PMID- 19162963
TI  - A wireless sensor network compatible wearable u-healthcare monitoring system
      using integrated ECG, accelerometer and SpO2.
AB  - This paper presents the design and development of a wearable ubiquitous
      healthcare monitoring system using integrated electrocardiogram (ECG),
      accelerometer and oxygen saturation (SpO(2)) sensors. In this design, non
      intrusive healthcare system was designed based on wireless sensor network (WSN)
      for wide area coverage with minimum battery power to support RF transmission. We
      have developed various devices such as wearable ubiquitous sensor network (USN)
      node, wearable chest sensor belt and wrist pulse oximeter for this system. Low
      power ECG, accelerometer and SpO(2) sensors board was integrated to the wearable
      USN node for user's health monitoring. The wearable ubiquitous healthcare
      monitoring system allows physiological data to be transmitted in wireless sensor
      network using IEEE 802.15.4 from on-body wearable sensor devices to a base
      station which is connected to a server PC. Physiological data can be displayed
      and stored in the server PC continuously.

PMID- 19162964
TI  - WSN based mobile u-healthcare system with ECG, blood pressure measurement
      function.
AB  - A mobile u-healthcare system with multiple physiological signs measurement
      capability in real time is designed and developed. This system performs local
      vital sign data analysis using a cellular phone and transmits data over a
      wireless sensor network. Electrocardiogram (ECG) and blood pressure signals of
      the patients are continuously be monitored, processed and analyzed locally at
      cellular phone to produce useful medical information for diagnosis and tracking
      purposes. When any unknown or suspected patterns of signals are detected,
      cellular phone performs some simple data analysis first and then immediately
      transmits these signals to a hospital server for clinicians' careful diagnosis.
      Implementation of wireless technology in the diagnosis system enables patient can
      be monitored anywhere, anytime and would not be impeded by the physical
      constraints imposed by the cables. This feature could prove helpful in fulfilling
      the vision of 'Pervasive Healthcare'.

PMID- 19162965
TI  - Energy efficient simulator for patient monitoring in Body Sensor Networks.
AB  - The medical tracking of patients carried out from a distance by means of wireless
      technology, incorporating various sensors simultaneously connected to the body of
      an individual, can promote health in suitable time. This article proposes a
      simulator for the monitoring of human health. This prototype simulates the
      workings of a BSN (Body Sensor Network) functioning as a sensor
      (electrophysiological signal) that is to be monitored, which utilizes a strategy
      based on the concept of data fusion. This tool incorporates a policy of
      economizing energy which has as its main objective increasing the operating time
      of the system.

PMID- 19162966
TI  - An energy-efficient communication method based on the relationships between
      biological signals for ubiquitous health monitoring.
AB  - Wireless sensor networks have been studied in the area of intelligent
      transportation systems, disaster perception, environment monitoring, ubiquitous
      healthcare, home network, and so on. For the ubiquitous healthcare, the previous
      systems collect the sensed health related data at portable devices without regard
      to correlations of various biological signals to determine the health conditions.
      It is not the energy-efficient method to gather a lot of information into a
      specific node to decide the health condition. Since the biological signals are
      related with each other to estimate certain body condition, it is necessary to be
      collected selectively by their relationship for energy efficiency of the
      networked nodes. One of researches about low power consumption is the reduction
      of the amount of packet transmission. In this paper, a health monitoring system,
      which allows the transmission of the reduced number of packets by means of
      setting the routing path considered the relations of biological signals, is
      proposed.

PMID- 19162967
TI  - The development of the friction coefficient inspection equipment for skin using a
      load cell.
AB  - The skin is an indispensible organ for human because it contributes to the
      metabolism using its own biochemical functions as well as it protects the human
      body from the exterior stimuli. Recently, the friction coefficient have been used
      as the decision index of the progress for the bacterial aliments in the field of
      the skin physiology and the importance of friction coefficient have been
      increased in the skin care market because of the needs of the well being times.
      In addition, the usage of friction coefficient is known to have the big
      discrimination ability in classification of human constitutions, which is
      utilized in the alternative medicine. In this study, we designed a system which
      used the multi axes load cell and hemi-circular probe and tried to measure the
      friction coefficient of hand skins repeatedly. Using this system, the relative
      repeatability error for the measurement of the friction coefficient was below 4
      %. The coefficient is not concerned in curvatures of tips. Using this system, we
      will try to establish the standard for classification of constitutions.

PMID- 19162968
TI  - Channel models for wireless body area networks.
AB  - Wireless patient monitoring using wearable sensors is a promising application.
      This paper provides stochastic channel models for wireless body area network
      (WBAN) on the human body. Parameters of the channel models are extracted from
      measured channel transfer functions (CTFs) in a hospital room. Measured frequency
      bands are selected so as to include permissible bands for WBAN; ultra wideband
      (UWB), the industry, science and medical (ISM) bands, and wireless medical
      telemetry system (WMTS) bands. As channel models, both a path loss model and a
      power delay profile (PDP) model are considered. But, even though path loss models
      are derived for the all frequency bands, PDP model is only for the UWB band due
      to the highly frequency selectiveness of UWB channels. The parameters extracted
      from the measurement results are summarized for each channel model.

PMID- 19162969
TI  - A novel network module for medical devices.
AB  - In order to allow medical devices to upload the vital signs to a server on a
      network without manually configuring for end-users, a new network module is
      proposed. The proposed network module, called Medical Hub (MH), functions as a
      bridge to fetch the data from all connecting medical devices, and then upload
      these data to the server. When powering on, the MH can immediately establish
      network configuration automatically. Network Address Translation (NAT) traversal
      is also supported by the MH with the UPnP Internet Gateway Device (IGD)
      methodology. Besides the network configuration, other configuration in the MH is
      automatically established by using the remote management protocol TR-069. On the
      other hand, a mechanism for updating software automatically according to the
      variant connected medical device is proposed. With this mechanism, newcome
      medical devices can be detected and supported by the MH without manual operation.

PMID- 19162970
TI  - U-healthcare System using Smart Headband.
AB  - The wearable healthcare system should be not only small and easy for users to
      wear them but accurate in measuring physiological signals in daily life without
      any inconvenience. To meet these requirements, we propose the U-healthcare System
      which consists of a Smart Headband and a Health-state Monitor program. It can
      monitor the health-state in walking and running. The Smart Headband measures a
      photo-plethysmography (PPG) signal at the forehead for monitoring the heart rate
      and acceleration signals. The Health-state Monitor program is developed to show
      the health-state. Health-state Monitor program is operated in the handheld
      computer, such like (Ultra Mobile Personal Computer (UMPC). It provides the user
      PPG, heart rate and steps for the precise measurement, Adaptive Noise
      Cancellation (ANC) is introduced. The Smart Headband and the Health-state Monitor
      program are communicated by the WPAN using Zigbee protocol. If the heart rate is
      higher or lower than usual, the Health-state Monitor program sends the SMS
      message to the designated person, such as family or the attending physician in
      the medical center, to inform the emergency situation.

PMID- 19162971
TI  - Real-time Ambulance Location Monitoring using GPS and Maps Open API.
AB  - The term 'Open API' has been recently in use by recent trends in social media and
      web 2.0. It is currently a heavily sought after solution to interconnect Web
      sites in a more fluid user-friendly manner. We could have benefits easily
      development and high efficiency.

PMID- 19162972
TI  - Career development in Bioengineering/Biomedical Engineering: a student's roadmap.
AB  - Bioengineering/biomedical engineering education has progressed since the late
      1950s and is still evolving in leading academic institutions worldwide. Today,
      Bioengineering/Biomedical Engineering is acclaimed as one of the most reputable
      fields within the global arena, and will likely be the catalyst for any future
      breakthroughs in Medicine and Biology. This paper provides a set of strategies
      and recommendations to be pursued by individuals aiming at planning and
      developing careers in this field. The paper targets the international student
      contemplating bioengineering/biomedical engineering as a career, with an
      underlying emphasis on the student within developing and transitional countries
      where career guidance is found deficient. The paper also provides a comprehensive
      definition of the field and an enumeration of its subdivisions.

PMID- 19162973
TI  - Design of experiments in Biomedical Signal Processing Course.
AB  - Biomedical Signal Processing is one of the most important major subjects in
      Biomedical Engineering. The contents of Biomedical Signal Processing include the
      theories of digital signal processing, the knowledge of different biomedical
      signals, physiology and the ability of computer programming. Based on our past
      five years teaching experiences, in order to let students master the signal
      processing algorithm well, we found that the design of experiments following
      algorithm was very important. In this paper we presented the ideas and aims in
      designing the experiments. The results showed that our methods facilitated the
      study of abstractive signal processing algorithms and made understanding of
      biomedical signals in a simple way.

PMID- 19162974
TI  - Electronics manufacturing infrastructures for education and commercialization.
AB  - Many medical and biological applications require custom integrated hardware.
      Infrastructures for the design of CMOS and MEMS hardware allow the education and
      commercialization at a low cost and in a short time. This paper is reviewing the
      most recent developments at CMP for the manufacturing of ICs and MEMS. These
      custom hardware vehicles allow to target many medical and biological
      applications. Examples are provided through the paper. Such infrastructures may
      help the Medical and Biological community the same way they helped the
      Microelectronics community at the time of the VLSI revolution.

PMID- 19162975
TI  - Computer-aided auscultation learning system for nursing technique instruction.
AB  - Pulmonary auscultation is a physical assessment skill learned by nursing students
      for examining the respiratory system. Generally, a sound simulator equipped
      mannequin is used to group teach auscultation techniques via classroom
      demonstration. However, nursing students cannot readily duplicate this learning
      environment for self-study. The advancement of electronic and digital signal
      processing technologies facilitates simulating this learning environment. This
      study aims to develop a computer-aided auscultation learning system for assisting
      teachers and nursing students in auscultation teaching and learning. This system
      provides teachers with signal recording and processing of lung sounds and
      immediate playback of lung sounds for students. A graphical user interface allows
      teachers to control the measuring device, draw lung sound waveforms, highlight
      lung sound segments of interest, and include descriptive text. Effects on
      learning lung sound auscultation were evaluated for verifying the feasibility of
      the system. Fifteen nursing students voluntarily participated in the repeated
      experiment. The results of a paired t test showed that auscultative abilities of
      the students were significantly improved by using the computer-aided auscultation
      learning system.

PMID- 19162976
TI  - New market, new challenge, new opportunity (1)--overview of China rural
      healthcare & design methodology.
AB  - China has a largest population in the world (1.3Billion) and 0.9 Billion is rural
      population. Most of rural people earn less than US$3/day, and they are called
      'Base of the economic pyramid (BoP)'. Compared with high level market, BoP is a
      new market, which means a low individual profit, but a large population. This
      paper discusses the healthcare issues in rural China (BoP) and study their
      healthcare needs through field study and case studies. This research is carried
      out within the framework of 'Design for Sustainability at Base-of-the-Pyramid
      (BoP)' programme of the School of Industrial Design Engineering at Delft
      University of Technology. And the aim of this research is to provide a low cost
      advanced healthcare product design, which will meet poor's needs and create a
      business case for commercial partners.

PMID- 19162977
TI  - New market, new challenge, new opportunity (2)--user context research.
AB  - China has a largest population in the world (1.3Billion) and 0.9 Billion is rural
      population. Most of rural people earn less than US$3/day, and they are called
      'Base of the economic pyramid (BoP)'. A new research project has been initiated
      on 'The Healthcare Design for China Rural BoP' to the PhD of first author. This
      paper is about one part of this research: user context research. Two main
      processes will be introduced in this step: Qualitative research and quantitative
      research. Some healthcare needs in China rural like 'Cancer early detection' has
      been found as the insights of this research.

PMID- 19162978
TI  - Service design projects sponsored by the Kansas State University Student Chapter
      of the IEEE EMBS.
AB  - Service projects offer volunteer student organizations a means to generate
      interest and focus activity outside of the context of the classroom. This paper
      addresses efforts by the Kansas State University (KSU) Student Chapter of the
      IEEE Engineering in Medicine and Biology Society (EMBS) to initiate and guide
      service projects in two primary areas: (1) research to aid persons with
      disabilities (RAPD) and (2) hands-on efforts to interest young women in the
      quantitative fields of science and engineering. Three RAPD projects are
      presented: a computer mouse design that helps to alleviate productivity problems
      associated with Parkinson's tremors, a battery removal tool for arthritic
      individuals with limited dexterity, and a wireless door control and communication
      system to assist mobility-limited individuals. Service projects to garner science
      and engineering interest in young women are co-sponsored by the KSU Women in
      Engineering and Science Program (WESP). The most recent activity, entitled 'Vital
      Signs Shirts,' is presented in this paper, along with a summary of pending
      interactive laboratories designed to interest participants in engineering as
      applied to the human body. These service projects encourage IEEE EMBS student
      chapter members to explore their biomedical engineering interests and make a
      positive impact in the community.

PMID- 19162979
TI  - Using heart rate monitors for personal wellness--the user experience perspective.
AB  - In this paper, we present a user study of the heart rate monitors (HRM), which is
      a commonly used personal wellness technology. HRMs have been used over several
      years for adjusting the exercise level and in the advanced form, also for
      measuring the users' fitness level and its progress. The user study included
      interviews with the HRM users and a survey with over 860 active or former users.
      We identified four different types of HRM users based on the current usage
      activity and their perceived progress of usage motivation within time, and
      compared their perceptions of the strengths and weaknesses related to HRMs. The
      findings provide valuable information for understanding the end-user needs and
      background knowledge for developing personal wellness technologies and
      applications further.

PMID- 19162980
TI  - The benefits of industry--university interaction.
AB  - Through participation in various activities, industry can influence the
      curriculum of Biomedical Engineering, provide feedback on how well students are
      prepared for careers in industry, and find well-prepared candidates for positions
      within the company. Universities can learn what current technologies are being
      used in industry and thus adapt their curriculum to meet the needs of industry.
      They can also acquire industry input to design and research projects and the
      monetary donations to fund the projects. Students can determine what area of
      industry they are most interested in, gain some experience in working in that
      area, find they do not like a particular area and explore other areas, and better
      prepare themselves for their careers. If additional biomedical companies and
      institutions of higher learning undertook this type of program, biomedical
      engineering would significantly improve and so would healthcare.

PMID- 19162981
TI  - Neuroengineering: building interfaces from neurons to brain.
AB  - Neuroengineering is emerging as an exciting new field with wide ranging research
      opportunities to contribute to both basic and clinical neurosciences. Armed with
      training and diverse research tools, engineers are now contributing to
      technologies to interface to neurons and to the whole brain. The research on
      modern neural and brain interface technologies has culminated in very recent,
      exciting programs to develop brain-machine interfaces such as neutrally
      controlled prostheses.

PMID- 19162982
TI  - Building a brain on a chip.
AB  - The wild idea that nerve cells grown in culture could have reliable computational
      function, while still a wild idea, is closer to reality than is reasonable to
      expect, thanks to applications of both engineering and applied biology. The
      metaphor works both ways: applications of more traditional engineering
      technologies - signal processing, electronics, microlithography, materials
      science - make possible the controlled growth, recording, and stimulation of
      nerve cells. In turn the goal is to design, construct, test, and utilize - in
      short to engineer - a working biological construct. In this lecture examples,
      mainly from the speaker's laboratory, illustrate the component technologies that
      have been utilized in this pursuit, as well as examples illustrating how the
      approaching the problem as an engineer leads to the asking new questions. The
      talk will include brief discussion of the problem of analyzing high dimensional,
      inherently non-stationary neural spike data.

PMID- 19162983
TI  - Model-based nonlinear optimal blood glucose control of type I diabetes patients.
AB  - Using induced L(2)-norm minimization, a robust controller was developed for
      insulin delivery in Type I diabetic patients. The high-complexity nonlinear
      diabetic patient Sorensen-model [1] was considered. LPV (Linear Parameter
      Varying) methodology was used to develop open loop model and robust controller.
      Considering the normoglycemic set point (81.1 mg/dL), a polytopic set was created
      over the physiologic boundaries of the glucose-insulin interaction of the
      Sorensen-model. In this way, LPV model formalism was defined. The robust control
      was developed considering input and output multiplicative uncertainties with
      other weighting functions.

PMID- 19162984
TI  - Novel polysomnography derived features as biomarkers for sleep dynamics.
AB  - We propose a generation of Polysomnography (PSG)-derived measures that can
      quantify temporal patterns of sleep, and investigate the role of these measures
      as predictors of hypertension. We also investigate the influence of age on these
      measures as compared to traditional indices. We perform cross-sectional analyses
      of the association between hypertension status with traditional PSG and novel
      measures using adjusted and unadjusted logistic regression models. Our findings
      suggest that when adjusted for common confounders such as age, gender, race and
      Body Mass Index (BMI) the new features that quantify the variability of the sleep
      process are more strongly associated with hypertension as compared to traditional
      PSG indices, and are not as strongly influenced by age as are the traditional
      indices. The result implies that the regularity of sleep dynamics may be an
      important feature associated with hypertension. These measures may provide a
      powerful tool for discriminating individuals at risk for comorbidities, such as
      hypertension, associated with sleep disturbances.

PMID- 19162985
TI  - Base lung sound in diffuse interstitial pneumonia analyzed by linear and
      nonlinear techniques.
AB  - Abnormal lung sounds in diffuse interstitial pneumonia have been characterized by
      the presence of crackles. However, few attempts have tried to analyze the sound
      where crackles are immersed. In this work base lung sounds (BLS) were analyzed by
      linear and nonlinear techniques to find possible differences between normal
      subjects and patients with diffuse interstitial pneumonia. In both groups,
      segments of lung sounds (crackles absent) and segments of BLS (lung sound in
      between crackles) were analyzed from acquired lung sounds from four points at the
      posterior chest, two apical and two basal. In this study, 8 healthy subjects and
      8 patients participated and BLS were analyzed by spectral percentiles and sample
      entropy. Although spectral percentiles and sample entropy (SampEn) tended to be
      lower in the group of patients, statistical differences (p0.05) between normal
      subjects and patients were found in BLS at the left hemithorax at basal and
      apical regions, while at the right hemithorax significant differences were found
      only at the basal region using the nonlinear technique. We conclude that in
      respect to normal subjects, BLS of patients with diffuse interstitial pneumonia
      present differences as assessed by SampEn, so that BLS by itself provides useful
      information. Moreover, it seems that nonlinear technique did a better
      discrimination of abnormal BLS than spectral percentile parameters.

PMID- 19162986
TI  - Nonlinear analysis of the ECG during atrial fibrillation in patients for low
      energy internal cardioversion.
AB  - The goal of this study was to investigate the usefulness of nonlinear analysis in
      determining the success of low energy internal cardioversion (IC) in patients
      with atrial fibrillation (AF). Nonlinear analysis has previously been used for
      characterizing AF patterns, and spontaneous termination in its paroxysmal form.
      However, the relationship between the probability to restore sinus rhythm by IC
      and quantitative nonlinear analysis based electrocardiographic (ECG) markers has
      not been explored before. Thirty nine patients with AF, for elective DC
      cardioversion at the Royal Victoria Hospital in Belfast, were included in this
      study. One catheter was positioned in the right atrial appendage and another in
      the coronary sinus, to deliver a biphasic shock waveform. A voltage step-up
      protocol (50-300 V) was used for patient cardioversion. Residual atrial
      fibrillatory signal (RAFS) was derived from 60 seconds of surface ECG from
      defibrillator pads, prior to shock delivery, by bandpass filtering and
      ventricular activity (QRST) cancellation. QRST complexes were cancelled using a
      recursive least squared (RLS) adaptive filter. The maximal Lyapunov exponent
      (lambda), correlation dimension (course grained estimation, CDcg) and approximate
      entropy (ApEn) were extracted from the RAFS. These variables were calculated from
      10 s of the RAFS before shock delivery. 26 patients were successfully
      cardioverted, employing a maximum energy of 11.84 joules. A lower lambda (0.037+/
      0.006 vs. 0.044+/-0.008, P=0.01) and CDcg (5.552+/-2.075 vs. 6.592+/-1.130,
      P=0.049) were found in successfully cardioverted patients than in those non
      successful ones, with an energy <or=3 joules. Also, there was a significant
      positive correlation between the minimal defibrillation energy and lambda
      (r=0.483, P=0.013) in cardioverted patients. In conclusion, complexity analysis
      of the RAFS is useful for assessing the prospective efficacy of internal low
      energy cardioversion of patients with atrial fibrillation.

PMID- 19162987
TI  - Feature extraction for murmur detection based on support vector regression of
      time-frequency representations.
AB  - This paper presents a nonlinear approach for time-frequency representations (TFR)
      data analysis, based on a statistical learning methodology - support vector
      regression (SVR), that being a nonlinear framework, matches recent findings on
      the underlying dynamics of cardiac mechanic activity and phonocardiographic (PCG)
      recordings. The proposed methodology aims to model the estimated TFRs, and
      extract relevant features to perform classification between normal and pathologic
      PCG recordings (with murmur). Modeling of TFR is done by means of SVR, and the
      distance between regressions is calculated through dissimilarity measures based
      on dot product. Finally, a k-nn classifier is used for the classification stage,
      obtaining a validation performance of 97.85%.

PMID- 19162988
TI  - Online cardiac arrhythmia classification by means of circle maps analysis
      implemented on an intelligent miniaturized sensor.
AB  - The intermittent occurrence of cardiac arrhythmias like e.g. atrial fibrillation
      hampers their diagnosis and hence the treatment. Since persons suffering from
      atrial fibrillation are known to have a remarkable increased risk of stroke the
      diagnosis of atrial fibrillation is a matter of great importance. Easy and
      comfortable to use long term ECG recording systems capable of online arrhythmia
      classification might help to solve this problem. We developed an intelligent,
      miniaturized, and wireless networking sensor which allows lossless local data
      recordings up to 4 GB. With its outer dimensions of 20mm per rim and less than
      15g of weight including the Lithium-Ion battery our modular designed sensor node
      is thoroughly capable of up to eight channel recordings with 8 kHz sample rate
      each and provides sufficient computational power for online digital signal
      processing. For online arrhythmia classification we will record one ECG channel
      and 3-axis accelerometer data with 512 Hz each, the later being used for activity
      classification based artifact identification. We adapted our recently developed
      circle maps analysis of short term heart rate variation to run on this
      miniaturized intelligent sensor powered by the Texas Instruments MSP430
      microcontroller derivate F1611. With this configuration we started to evaluate
      the cardiac arrhythmia classification in long term ECG recordings.

PMID- 19162989
TI  - Adaptive hybrid system for automatic sleep staging.
AB  - We present a new adaptive system for automated sleep staging. The proposed system
      relies on each subject's own data for self-training. Conventional automatic sleep
      staging algorithms are either rule based, which typically fail to accurately
      model the complex nature of sleep signals, or numerical methods that use multi
      patient training schemes, which suffer from inaccuracies caused by inherent inter
      patient variability. The proposed system employs two stages. The first stage is a
      rule based reasoning engine that can be tuned conservatively to decrease or
      eliminate false positives, generating just enough samples to train the second
      stage, which is comprised of a neural network classifier. Results show that this
      hybrid approach provides an adaptive training scheme that performs more
      accurately compared to one of the popular commercially available systems.

PMID- 19162990
TI  - HMM-based estimation of menstrual cycle from skin temperature during sleep.
AB  - An HMM-based method is proposed to estimate biphasic property in female menstrual
      cycle. A tiny device is developed to measure skin temperature change during
      sleep. Data are collected from 30 female participants for 6 months. Raw data are
      preprocessed to remove obvious outliers and clamped between 34 and 42 degree
      Celsius. A two hidden states HMM-based algorithm was applied to estimate the
      biphasic property in menstrual cycle. The results showed that the number of
      correctly detected menstrual cycle is 159 among 173 in 30 participants during 6
      months. Overall sensitivity reaches 92.0%.

PMID- 19162991
TI  - Automatic sleep detection using activity and facial electrodes.
AB  - The most commonly applied unobtrusive sleep monitoring method is actigraphy, the
      measurement of body limb movements. In spite of its wide clinical acceptance,
      actigraphy has a low specificity for sleep detection leaving room for novel
      approaches of unobtrusive sleep monitoring. The present study compared sleep
      detection by a novel single channel electro-oculography (EOG) method and three
      activity monitors, with the golden standard of polysomnographic sleep analysis as
      a reference. With standard actigraphy (Actiwatch placed at the left wrist) sleep
      detection specificity and sensitivity were 42% and 95%. With the Alive Monitor
      attached on the same wrist, activity-based sleep detection specificity and
      sensitivity were 40% and 97%. With another Alive Monitor placed over the sternum
      sleep detection specificity and sensitivity were 21% and 99%. With two self
      applied EOG electrodes combined with automatic sleep detection analysis,
      specificity and sensitivity were 72% and 96%. The results confirm low specificity
      of actigraphic sleep estimates, and demonstrate that the novel single-channel EOG
      method provides a substantial improvement in specificity.

PMID- 19162992
TI  - Automatic sleep stage classification using two facial electrodes.
AB  - Standard sleep stage classification is based on visual analysis of central EEG,
      EOG and EMG signals. Automatic analysis with a reduced number of sensors has been
      studied as an easy alternative to the standard. In this study, a single-channel
      electro-oculography (EOG) algorithm was developed for separation of wakefulness,
      SREM, light sleep (S1, S2) and slow wave sleep (S3, S4). The algorithm was
      developed and tested with 296 subjects. Additional validation was performed on 16
      subjects using a low weight single-channel Alive Monitor. In the validation
      study, subjects attached the disposable EOG electrodes themselves at home. In
      separating the four stages total agreement (and Cohen's Kappa) in the training
      data set was 74% (0.59), in the testing data set 73% (0.59) and in the validation
      data set 74% (0.59). Self-applicable electro-oculography with only two facial
      electrodes was found to provide reasonable sleep stage information.

PMID- 19162993
TI  - Using psychoacoustics of snoring sounds to screen for obstructive sleep apnea.
AB  - This paper aims to develop a reliable psychoacoustic evaluation tool for
      measuring snoring sounds. Thirteen snoring sound samples were assessed by 25
      listeners, in terms of psychoacoustic metrics (loudness, sharpness, roughness,
      fluctuation strength, and annoyance) using a 7-point semantic differential scale
      with bipolar adjective pairs. The accuracy of this study was quantified by
      receiver operating characteristic curves, together with Pearson's product-moment
      and Spearman's rank correlation coefficients. Results consistently show that
      loudness, annoyance, and roughness are the best three metrics for classifying
      apneic and benign snorers as they can achieve high diagnostic accuracy and good
      correlation with apnea-hypopnea index, body mass index, and neck circumference.
      With these encouraging results, further research and development of an effective
      psychoacoustic evaluation tool is promising.

PMID- 19162994
TI  - Single layer network classifiers to assist in the detection of obstructive sleep
      apnea syndrome from oximetry data.
AB  - The aim of this study is to assess the utility of single layer network
      classifiers to help in the diagnosis of the obstructive sleep apnea syndrome
      (SAOS). Oxygen saturation (SaO(2)) recordings from a total of 157 subjects
      suspected of suffering from OSAS were used. These were divided into a training
      set and a test set with 74 and 83 subjects, respectively. Four classification
      schemes were developed by using generalized linear models (GLM). Two GLM
      classifiers were built with spectral (GLM-SP) and non-linear (GLM-NL) features
      from SaO(2) signals, respectively. In addition, both algorithms were combined in
      order to improve their classification capability. The performance of two
      different ensemble classifiers was analyzed. The highest diagnostic accuracy was
      reached by the GLM-SP classifier (88%). The ensemble built from the combination
      of GLM-SP and GLM-NL by means of an additional GLM structure provided the best
      sensitivity value (87.8%). Applying spectral and non-linear features from SaO(2)
      data simultaneously could be useful in OSAS diagnosis.

PMID- 19162995
TI  - A new method in accelerating PROPELLER MRI.
AB  - In this work, a new method has been proposed to accelerate the PROPELLER MRI
      operation. The proposed method uses a rotary phased array coil and a new method
      in acquiring the k-space strips and preparing the complete k-space trajectories
      data set. It is numerically shown that for a 12 strips PROPELLER MR brain imaging
      sequence, the operation time can be reduced by four folds, with no apparent loss
      in the image quality.

PMID- 19162996
TI  - Block circulant quasi-band matrix property for the SENSE unfolding in k-space and
      justification for GRAPPA.
AB  - The k-space unfolding matrix for parallel imaging in MRI was examined and was
      found to have the structure of block circulant quasi-band, providing a rigorous
      mathematical justification for the interpolation kernel in the commonly used
      GRAPPA method. The optimal GRAPPA kernel size and dimension were closely related
      to sensitivity spectrum.

PMID- 19162997
TI  - 2D adaptive coil sensitivity estimation for dynamic parallel MRI reconstruction.
AB  - Incorporation of parallel imaging technique in dynamic magnetic resonance imaging
      process accelerates significantly the imaging speed. The acceleration is achieved
      by acquiring the k-space data sparsely in each frame. To unwrap the aliased
      images caused by the k-space under-sampling, the reconstruction algorithms need
      the local sensitivity variation, the sensitivity map, of the receiving coils.
      Current estimation methods are unable to provide the true sensitivity map, and
      the calibration errors in the estimated sensitivity map can dramatically increase
      the image artifacts. This paper introduces a novel two-dimensional k-t modeling
      approach to improve the estimation of sensitivity map. A 2D model is fitted to
      each k-t plane and is updated for each estimated data point. The model is used to
      estimate the unacquired k-space data in each frame. A full k-t plane is composed
      using the estimated and acquired datasets and is used to obtain improved
      estimation of sensitivity map. Experiments on real dynamic parallel MRI data
      demonstrate that the proposed method significantly improve the quality of
      reconstructed MR images.

PMID- 19162998
TI  - Accelerating sensitivity encoding using compressed sensing.
AB  - The combination of Compressed Sensing (CS) and SENSitivity Encoding (SENSE) for
      improving MRI acquisition speed and robustness has recently drawn great
      attentions. However, in the direct combination, the encoding matrix which
      represents the Fourier transform of channel-specific sensitivity modulation is
      not guaranteed to be a good CS matrix. In this paper, we propose a different
      approach that applies CS and SENSE sequentially. The method first uses CS to
      reconstruct a set of aliased images in each coil, and then applies the basic
      SENSE on these images to reconstruct the final image. The total reduction factor
      can achieve the product of the factors of each individual method. The
      experimental results show that overall performance of our proposed method is
      superior to the direct combination method with the same reduction factor.

PMID- 19162999
TI  - Compressed sensing parallel magnetic resonance imaging.
AB  - Both parallel Magnetic Resonance Imaging (pMRI) and Compressed Sensing (CS) can
      significantly reduce imaging time in MRI, the former by utilizing multiple
      channel receivers and the latter by utilizing the sparsity of MR images in a
      transformed domain. In this work, pMRI and CS are integrated to take advantages
      of the sensitivity information from multiple coils and sparsity characteristics
      of MR images. Specifically, CS is used as a regularization method for the inverse
      problem raised by pMRI based on the L1 norm and a Total Variation (TV) term. We
      test the new method with a set of 8-channel, in-vivo brain MRI data at reduction
      factors from 2 to 8. Reconstruction results show that the proposed method
      outperforms several other regularized parallel MRI reconstruction such as the
      truncated Singular Value Decomposition (SVD) and Tikhonov regularization methods,
      in terms of residual artifacts and SNR, especially at reduction factors larger
      than 4.

PMID- 19163000
TI  - K-space and image space combination for motion artifact correction in multicoil
      multishot diffusion weighted imaging.
AB  - Motion during diffusion encodings leads to phase errors in different shots of a
      multishot acquisition. Phase differences in k-space data among shots result in
      phase cancellation artifacts in the reconstructed image. Due to aliasing of the
      phase from under-sampled regions of the shot, correction of the phase error using
      direct low-resolution phase subtraction is incomplete. We introduce a new k-space
      and image-space combination (KICT) method for motion artifacts cancellation that
      avoids incomplete phase error correction. Further, the method preserves the phase
      of the object, which is important for parallel imaging applications.

PMID- 19163001
TI  - A fast Gauss-Newton optimizer for estimating human body orientation.
AB  - This paper presents a quaternion-based Gauss-Newton optimizer for tracking human
      body orientation using inertial/magnetic sensors. Since a computationally
      efficient and robust algorithm for estimating orientation is critical for low
      cost and real-time ambulatory purposes, the optimizer is formulated using a
      virtual rotation concept in order to decrease the computing time. In addition, to
      guard against the effects of fast body motions and temporary ferromagnetic
      disturbances, a situational measurement vector selection procedure is adopted in
      conjunction with the Gauss-Newton optimizer.

PMID- 19163002
TI  - Low-power signal processing devices for portable ECG detection.
AB  - An analog front end for diagnosing and monitoring the behavior of the heart is
      presented. This sensing front end has two low-power processing devices, including
      a 5(th)-order Butterworth operational transconductance-C (OTA-C) filter and an 8
      bit successive approximation analog-to-digital converter (SAADC). The components
      fabricated in a 0.18-microm CMOS technology feature with power consumptions of
      453 nW (filter) and 940 nW (ADC) at a supply voltage of 1 V, respectively. The
      system specifications in terms of output noise and linearity associated with the
      two integrated circuits are described in this paper.

PMID- 19163003
TI  - The deployment of a non-intrusive alternative to sleep/wake wrist actigraphy in a
      home-based study of the elderly.
AB  - This paper reports on experimental trials with an Under Mattress Bed Sensor
      (UMBS), an easily deployable, non-contact, low cost alternative to the actigraphy
      watch for sleep monitoring. Results from a home-based study of elderly subjects
      confirm accurate temporal resolution of activity monitoring in bed. UMBS activity
      classification thresholds were determined by maximizing Matthew's Correlation
      Coefficient between the activity data captured using an actigraphy watch and the
      proposed sensor. Preliminary results on a healthy young subject showed very high
      agreement rates justifying its use as a replacement for wrist actigraphy.

PMID- 19163004
TI  - Continuous cuff-less blood pressure monitoring based on the pulse arrival time
      approach: the impact of posture.
AB  - There is an unmet need for cuff-less blood pressure (BP) monitoring especially,
      in personal healthcare applications. The pulse arrival time (PAT) approach might
      offer a suitable solution to enable comfortable BP monitoring even at beat-level.
      However, the methodology is based on hemodynamic surrogate measures, which are
      sensitive to patient activities such as posture changes, not necessarily related
      to blood pressure variations. In this paper, we analyze the impact of posture on
      the PAT measure and related hemodynamic parameters such as the pre-ejection
      period in well-defined procedures. Additionally, the PAT of a monitored subject
      is investigated in an unsupervised scenario illustrating the complexity of such a
      measurement. Our results show the failure of blood pressure inference based on
      simple calibration strategies using the PAT measure only. We discuss
      opportunities to compensate for the observed effects towards the realization of
      wearable cuff-less blood pressure monitoring. These findings emphasize the
      importance of accessing context information in personal healthcare applications,
      where vital sign monitoring is typically unsupervised.

PMID- 19163005
TI  - Reliable motion artifact detection for ECG monitoring systems with dry
      electrodes.
AB  - Reliable signals are the basic prerequisite for most mobile ECG monitoring
      applications. Especially when signals are analyzed automatically, capable motion
      artifact detection algorithms are of great importance. This article presents
      different artifact detection algorithms for ECG systems with dry electrodes. The
      algorithms are based on the measurement of additional parameters that are
      correlated with the artifacts. We describe a mobile measurement system and the
      procedure used for the evaluation of these algorithms. The algorithms are
      assessed based upon their effect on QRS detection. The best algorithm improved
      sensitivity (Se) from 98.7% to 99.8% and positive predictive value (+P) from
      98.3% to 99.9%, while 15% of the signal was marked as artifact. This corresponds
      to a decrease in false positive and false negative detected beats by 89.9%.
      Different metrics to evaluate the performance of an artifact detection algorithm
      are presented.

PMID- 19163006
TI  - Remote health monitoring with wearable non-invasive mobile system: The HealthWear
      project.
AB  - This paper focuses on the technical solutions enabling the monitoring of health
      conditions by means of ECG, HR, oxygen saturation, impedance pneumography and
      activity patterns. The Healthwear service is based on the Wealthy prototype
      system. A new design has been made to increase comfort in wearing of the system
      during daily patient activities. The cloth is connected to a patient portable
      electronic unit (PPU) that acquires and elaborates the signals from the sensors.
      The PPU transmits the signal to a central processing site through the use of GPRS
      wireless technology. This service is applied to three distinct clinical contexts:
      rehabilitation of cardiac patients, following an acute event; early discharge
      program in chronic respiration patients; promotion of physical activity in
      ambulatory stable cardio-respiratory patients.

PMID- 19163007
TI  - Towards closed-loop decoding of dexterous hand movements using a virtual
      integration environment.
AB  - It has been shown that Brain-Computer Interfaces (BCIs) involving closed-loop
      control of an external device, while receiving visual feedback, allows subjects
      to adaptively correct errors and improve the accuracy of control. Although closed
      loop cortical control of gross arm movements has been demonstrated, closed-loop
      decoding of more dexterous movements such as individual fingers has not been
      shown. Neural recordings were obtained from rhesus monkeys in three different
      experiments involving individuated flexion/extension of each finger, wrist
      rotation, and dexterous grasps. Separate decoding filters were implemented in
      Matlab's Simulink environment to independently decode this suite of dexterous
      movements in real-time. Average real-time decoding accuracies of 80% was achieved
      for all dexterous tasks with as few as 15 neurons for individual finger
      flexion/extension, 41 neurons for wrist rotation, and 79 neurons for grasps. In
      lieu of the availability of advanced multi-fingered prosthetic hands, real-time
      visual feedback of the decoded output was provided through actuation of a virtual
      prosthetic hand in a Virtual Integration Environment. This work lays the
      foundation for future closed-loop experiments with monkeys in the loop and
      dexterous control of an actual prosthetic limb.

PMID- 19163008
TI  - EVestG: responses in depressed patients.
AB  - Depression is a mood disorder characterized by a sustained period of low mood or
      loss of interest or pleasure in activities. Dysfunction of the limbic system is
      implicated in depression. Different areas of this system have bidirectional links
      with the vestibular nucleus. The diagnosis of depression is subjective.
      Electrovestibulography (EVestG) might be able to assist in the diagnosis of
      depression in a more objective way. A dynamic measure of the excitatory
      (ipsilateral) responses during the background, acceleration and deceleration
      phases of an active tilt are compared with a small group (n=5) of depressive
      patients and age matched controls (n=10).

PMID- 19163009
TI  - Instantaneous frequency and amplitude modulation of EEG in the hippocampus
      reveals state dependent temporal structure.
AB  - EEG and LFP activity reflect the dynamic and organized interactions of neural
      ensembles; therefore, it may be possible to use the features of brain rhythms to
      determine the computational state of a neuronal network. When neuronal networks
      are activated, physical principles predict that the frequency content of the
      field potential should reflect the network state, per se, and ergo the state
      transition. A novel way for characterizing brain states is by quantifying the
      temporal structure of AM and FM activity (change in amplitude and frequency over
      time) for brain rhythms of interest. The concept of AM and FM, in the
      quantitative sense, is virtually unexplored in systems neuroscience. This is not
      surprising considering estimation of FM activity requires fine temporal and
      precise estimation of instantaneous frequency. For AM activity, the absolute
      value of the Hilbert transform is sufficient. Here, we outline a practical pole
      tracking algorithm which uses a Kalman filter for univariate AR processes to
      estimate instantaneous frequency. We demonstrate the filter performance using
      simulated chirp and real EEG/LFP data recorded from the rat hippocampus; and show
      that AM/FM activity in EEG/LFP is temporally structured and dependent on
      behavioral and cognitive state. This algorithm has the potential to be a
      practical tool for characterizing fundamental structure in electrophysiology data
      and classifying computational states in the brain.

PMID- 19163010
TI  - A neuron signature based spike feature extraction algorithm for on-chip
      implementation.
AB  - A spike derivative based feature extraction algorithm is reported in this paper.
      The theoretical framework includes neuronal geometry signatures and noise
      shaping. Through evaluating neuronal geometry signatures with compartment model,
      we obtain improved differentiation among similar spikes by emphasizing high
      frequency signal spectrum. Through studying the noise properties, we find the
      total noise reduces by taking the derivative of spikes, which is the simplest
      frequency shaping filter boosting the high frequency signal spectrum. In
      addition, a preliminary hardware implementation to extract spike features has
      been realized using an integrated microchip interfaced with a personal computer.

PMID- 19163011
TI  - Tracking the non-stationary neuron tuning by dual Kalman filter for brain machine
      interfaces decoding.
AB  - Previous decoding approaches assume stationarity of the functional relationship
      between the neural activity and animal's movement in brain machine interfaces
      (BMIs). Studies show that the activity of individual neurons changes considerably
      from day to day. We propose to implement a dual Kalman structure to track neural
      tuning during the decoding process. While the kinematics are inferred as the
      state from the observation of neuron firing rates, the preferred direction of
      neuron tuning is also optimized by dual Kalman filtering on the linear
      coefficients of the observation model. When compared with the fixed tuning Kalman
      filter, the decoding performance of the adaptive dual Kalman filter is better
      (less Normalized Mean Square Error), which means that the evolving tuning of
      motor neuron is being tracked.

PMID- 19163012
TI  - Principal component analysis of M1 neurophysiology data suggests a motor-control
      system-architecture template.
AB  - Stereotyped reaching tasks are used to study how primate subjects learn and
      recall motor skills required to compensate for different external forces during
      arm movements. To unveil mechanisms accounting for skilled performance under a
      wide range of rapidly switching task dynamics conditions, we recorded neural data
      from the primary motor-cortex (M1). Here we present a systematic analysis of
      changes in the M1 activity of a monkey with extensive practice compensating for
      five different dynamic fields in an elbow flexion/extension task. We show how
      they reflect differences in task kinematics and dynamics. Making extensive use of
      principal component analysis (PCA) and in preparation for computational modeling
      (see the companion paper) we demonstrate how M1 activity can be related
      functionally to the dynamics of feed-forward (FF), fast- and slow- feedback (FB)
      loops of the adaptive controller implemented by the brain to guide skilled motor
      behavior.

PMID- 19163013
TI  - Cardiac differentiation of embryonic stem cells with point-source electrical
      stimulation.
AB  - The use of pluripotent stem cells as a means to repair damaged heart tissue has
      recently emerged as a promising, yet controversial therapy. Despite the different
      approaches and the variety of cell types used, many of these procedures have been
      met with mixed success. The lack of understanding of the differentiation and
      integration process, notably with respect to electrical signaling, significantly
      hampers the development of these therapies. A system was thus developed allowing
      the use of point source electrical stimulation on embryonic stem (ES) cells to
      study the effect of physiologically-relevant electrical stimulus. When modulating
      the amplitude of the stimulus over various differentiation stages of embryonic
      stem cells, differences in the proportions of cardiomyocytes to embryonic stem
      cells were observed through quantitative PCR. The use of this technique might
      have larger applications in understanding molecular pathways towards the
      regeneration process.

PMID- 19163014
TI  - Phase angle shift is a better determinant for catheter electrode contact with
      tissue compared to a catheter sensed electrogram.
AB  - Convention holds that the magnitude of an electrogram (EGM) recorded from an
      ablation catheter indicates proximity to the tissue and may be used to guide tip
      placement. The shift in capacitance (phase angle) as the electrode touches the
      tissue may be a better guide. We compared these two methods over a range of
      distances in close proximity to heart tissue. This study suggests that EGM is not
      a reliable predictor of proximity to tissue within a few millimeters of the
      surface. Thus, EGM alone should not be used to guide electrode placement for
      ablation, as a millimeter off the surface will shift a greater percentage of
      delivered energy to the blood pool rather than the target tissue. EGM should also
      not be used to gauge force of the catheter into tissue. Phase angle is a better
      predictor of both variables, but an optimal combination of predictors remains to
      be found.

PMID- 19163015
TI  - A simulation framework for dual chamber heart rhythm and cardiac pacing.
AB  - A previously developed open source computer model allows realistic simulation of
      ventricular intervals in atrial fibrillation, while taking into account of
      ventricular pacing. In this paper, we further improve this model and present a
      new simulation framework based on an integrated dual-chamber heart and pacer
      (IDHP) model. The IDHP model incorporates more realistic atrial and ventricular
      rhythm generators and an industry-standard dual-chamber pacemaker timing control
      logic. Moreover, it simulates various interactions between intrinsic heart
      activity and extrinsic cardiac pacing. The IDHP model provides a new simulation
      platform where it is possible to bench test advanced pacemaker algorithms in the
      presence of different types of cardiac rhythms.

PMID- 19163016
TI  - Comparison of the electrophysiologically based optimization methods with
      different pacing parameters in patient undergoing resynchronization treatment.
AB  - Many studies conducted on patients suffering from congestive heart failure have
      shown the efficacy of cardiac resynchronization therapy (CRT). The presented
      research investigates an off-line optimization algorithm based on different
      electrode positioning and timing delays. A computer model of the heart was used
      to simulate left bundle branch block (LBBB), myocardial infarction (MI) and
      reduction of intraventricular conduction velocity in order to customize the
      patient symptom. The optimization method evaluates the error between the healthy
      heart and pathology with/without pacing in terms of activation time and QRS
      length. Additionally, a torso model of the patient is extracted to compute the
      body surface potential map (BSPM) and to simulate the ECG with Wilson leads to
      validate the results obtained by the electrophysiological heart model
      optimization.

PMID- 19163017
TI  - Simultaneous double external DC shock techniques for atrial fibrillation: a
      simulation study.
AB  - The success rate of direct current cardioversion (DCC), the most common method to
      convert atrial fibrillation (AF) to sinus rhythm (SR), depends on various factors
      including AF duration, prior anti-arrhythmic therapy, electrode position and
      size, transthoracic impedance, and the use of biphasic versus monophasic shocks.
      Recent, small clinical studies have reported using quadruple electrodes to
      deliver higher energy, in order to increase DCC success rates in refractory
      patients. This study aims to computationally model and compare double shock
      defibrillation with conventional single shock DCC, based on the two parameters,
      defibrillation threshold (DFT) and heterogeneity index (HI). DFT is the energy
      required to achieve a voltage gradient of 5 V/cm over 95% of the atrial
      myocardium. HI, calculated as the (95(th)-5(th))/50(th) percentile of atrial
      electric field magnitudes, is a measure of non-uniformity. The electric field
      distributions in the myocardium were generated for over five thousand different
      conventional and quadruple electrode placements with electrodes of two different
      sizes. Results show that there is a significant decrease in DFT (p0.01) and HI
      (p0.01) with increase in electrode size and quantity.

PMID- 19163018
TI  - Physiological state characterization by clustering heart rate, heart rate
      variability and movement activity information.
AB  - The objective is to identify whether it is possible to discriminate between
      normal and abnormal physiological state based on heart rate (HR), heart rate
      variability (HRV) and movement activity information in subjects with
      cardiovascular complications. HR, HRV and movement information were obtained from
      cardiac patients over a period of 6 weeks using an ambulatory activity and single
      lead ECG monitor. By applying k-means clustering on HR, HRV and movement
      information obtained from cardiac patients, we obtained 3 clusters in inactive
      state and one cluster in active state. Two clusters in inactive state
      characterized by - a) high HR and low HRV b) low HRV and low HR, could be
      inferred as pathological with abnormal autonomic function. Further, activity
      information was significant in differentiating between the normal cluster found
      in active and an abnormal cluster found in inactive states, both with low HRV.
      This indicates that the activity information must be taken into account while
      interpreting HR and HRV information.

PMID- 19163019
TI  - Online pathological tremor characterization using extended Kalman filtering.
AB  - This paper describes different algorithms that perform online pathological tremor
      characterization in terms of acceleration. Two distinct parametricmodels are
      used, an Auto-Regressive (AR) model and an harmonic model. Both models are
      recursively estimated with Extended Kalman Filters (EKFs). Experimental data was
      obtained with low cost sensors and the results are compared in terms of
      spectrogram estimation and prediction performance.

PMID- 19163020
TI  - EEG and MRI data fusion for early diagnosis of Alzheimer's disease.
AB  - The prevalence of Alzheimer's disease (AD) is rising alarmingly as the average
      age of our population increases. There is no treatment to halt or slow the
      pathology responsible for AD, however, new drugs are promising to reduce the rate
      of progression. On the other hand, the efficacy of these new medications
      critically depends on our ability to diagnose AD at the earliest stage. Currently
      AD is diagnosed through longitudinal clinical evaluations, which are available
      only at specialized dementia clinics, hence beyond financial and geographic reach
      of most patients. Automated diagnosis tools that can be made available to
      community hospitals would therefore be very beneficial. To that end, we have
      previously shown that the event related potentials obtained from different scalp
      locations can be effectively used for early diagnosis of AD using an ensemble of
      classifiers based decision fusion approach. In this study, we expand our data
      fusion approach to include MRI based measures of regional brain atrophy. Our
      initial results indicate that ERPs and MRI carry complementary information, and
      the combination of these heterogeneous data sources using a decision fusion
      approach can significantly improve diagnostic accuracy.

PMID- 19163021
TI  - Submovements in visually-guided and memory-guided reaching tasks: changes in
      Parkinson's disease.
AB  - Movements in people with Parkinson's disease are often hypometric, although we
      have found that this was not the case in an experimental visually-guided reaching
      task. We wished to explore our hypotheses that (1) people with Parkinson's
      disease produce hypometric primary submovements but(2) are able to use visual
      feedback to accurately reach the target in a single overall movement, and (3)
      this effect may be greater in memory-guided tasks in which an internal
      representation of the target location is used instead of a fixation-centered
      representation of the target.Visually- and memory-guided reaching movements were
      examined in 22 people with mild to moderate severity Parkinson's disease on
      medication, along with age-matched and sex-matched controls. Primary submovements
      were extracted from 5149 movements using a method based upon zero crossings of
      jerk(3rd derivative of position), with several additional criteria to minimize
      the detection of submovements due to noise or tremor.There was no difference in
      the end position of the overall reaching movement between the two groups,
      although the movement was smaller in the memory-guided task. In contrast,the gain
      of the primary submovement was smaller in the Parkinson's disease group than the
      control group, with this difference being greater on the memory-guided task.
      There was no task effect on the primary submovement gain in the control group.Our
      results show that the underlying primary submovement in visually-guided movements
      in people with Parkinson's disease is hypometric, and that the degree of
      hypometria is even greater in memory-guided movements.

PMID- 19163022
TI  - Analysis of spatial temporal plantar pressure pattern during gait in Parkinson's
      disease.
AB  - Spatial temporal plantar pressure patterns measured with sheet-shaped pressure
      sensor were investigated to extract features of gait in Parkinson's disease. Both
      six subjects of Parkinson's disease (PD) and elderly fourteen normal control
      subjects were asked to execute usual walking on the pressure sensor sheets.
      Candidate features were step length, step time, gait velocity and transition of
      center of pressure to foot axis direction. The step length and gait velocity were
      smaller in PD subjects than those in normal subjects. Time of step cycle in three
      PD subjects were longer than that in normal subjects while the times of other PD
      subjects were similar to those of control subjects. The length from heel contact
      to toe off within one footprint was small in the subjects with short step length.
      Such possibility was indicated that Parkinson's disease in gait could be
      separated from normal subjects by these features.

PMID- 19163023
TI  - Quantifying drug induced dyskinesia in Parkinson's disease patients using
      standardized videos.
AB  - This paper presents a video based method to quantify drug induced dyskinesias in
      Parkinson's disease (PD) patients. Dyskinetic movement in standard clinical
      videos of patients is analyzed by tracking landmark points on the video frames
      using non-rigid image registration. The novel application of Point Distribution
      Models (PDM) allows geometric variations and covariations of the landmark points
      to be captured from each video sequence. The PDM parameters represent
      quantifiable information that can be used to rate dyskinesia effectively,
      analogously to a neurologist's strategy of assessing the movement of multiple
      body parts simultaneously to effectively rate dyskinesia. A heuristic decision
      function is then developed using the PDM parameters to quantify the severity of
      the dyskinesia. The severity score using our decision function showed a high
      correlation to the dyskinesia rating of a neurologist on the corresponding
      patient videos.

PMID- 19163024
TI  - Hardware-program complex for inspection of eyes, head and hand movements
      coordination of the man.
AB  - It is presented hardware- program complex for eyes, head and hand separate
      movement's check-up, and their coordination check-up in the integrated movement
      act. Patients with movement disorders are surveyed by using this complex. As an
      example there are shown differences in movement parameters value (a stage of
      latency, duration, frequency etc.), of patients with different stages of
      Parkinson disease (PD) by using several tests. Analysis of head, eyes and hand
      movement's trajectories can be used for early PD diagnostics.

PMID- 19163025
TI  - Objective estimation of the listening effort: towards a neuropsychological and
      neurophysical model.
AB  - Modern hearing aid fitting could be revolutionized by the availability of
      objective methods for the listening effort estimation. However experimental and
      theoretical research dealing with this subject is still in its infancy. In this
      paper we present first results towards a neuropsychological and neurophysical
      model for the objective estimation of the listening effort by
      electroencephalographic data. Our model is based on intended endogenously driven
      top-down projections represented by corticothalamic feedback dynamics for
      auditory stream selection and their large-scale correlates in auditory evoked
      late responses. The predictions of the presented model are compared to
      experimental data obtained during different auditory tasks which required a
      graduated effort for their solutions. The experimental data verified the model
      predictions.It is concluded that the proposed neuropsychological and
      neurophysical modeling of stream selection provides an appropriate framework for
      listening effort estimation. The presented preliminary results of an ongoing
      study are encouraging,however, further focal research is necessary in order to
      estimate in how far the presented model and future extensions might support
      modern hearing aid fitting in practice.

PMID- 19163026
TI  - In vivo study of response threshold in retinal degenerate model at different
      degenerate stages.
AB  - Retinal prostheses are being developed to apply electrical stimulation to the
      retina in order to restore vision of individuals who suffer from diseases such as
      retinitis pigmentosa (RP) and aged related macular degeneration (AMD). Various
      electrical stimulus parameters have been extensively studied in both experimental
      and clinical settings. Both electrophysiological and psychophysical results have
      shown that outer retina disease exhibit higher stimulus threshold in one
      degenerate group versus the control group. Fewer studies have been conducted to
      investigate the change in threshold currents as a function of different
      degenerate stages. We propose to study the electrophysiological change in
      degenerate rat retinas by using an in vivo recording method. We recorded retinal
      driven superior colliculus cells response in two control groups and four
      degenerate groups. Current pulses of seven different stimulus pulse durations
      were applied to the retinas to obtain strength duration curve per group.
      Preliminary results showed that for the postnatal (P) day 90 and 180 degenerate
      groups, threshold currents were not significantly different from the normal
      control group (P90 and P230). For P300 degenerate group, the threshold currents
      progressively increased. For P760 degenerate group, threshold currents were
      significantly elevated across all the stimulus pulse durations tested. Charge
      densities calculated for P760 degenerate group exceeded the safe limit of the
      stimulating electrode. Cell morphology in all control and degenerate groups is
      still under investigation for a correlation study.

PMID- 19163027
TI  - Retinal prosthesis phosphene shape analysis.
AB  - A retinal prosthesis system to restore sight for the blind is under development.
      The system is analogous to cochlear implants, in which photoreceptor input is
      bypassed and replaced by direct electrical stimulation of the retinal ganglion
      cells. Currently, six test subjects have been implanted with a 4x4 electrode
      array and stimulator. We report here psychophysical clinical data examining how
      stimulation amplitude affects phosphene shape and repeatability on a single
      electrode. Phosphene shape data was quantified by a set of numerical descriptors
      calculated from image moments. Comparison of phosphene descriptors for a single
      electrode across repeated trials and amplitude levels measured the repeatability
      within an amplitude group. Our experimental findings show that stimulation of the
      retina creates repeatable percept shapes and that an increase in stimulation
      amplitude causes a significant change in size and shape of phosphenes.

PMID- 19163028
TI  - Efficacy of supra-choroidal, bipolar, electrical stimulation in a vision
      prosthesis.
AB  - The key to successful, clinical application of therapeutic neurostimulators lies
      primarily with the safety and efficacy of their electrode-tissue interfaces. The
      authors posit that for electrical stimulation of the visual system, supra
      choroidal electrode placement provides a safe, stable and readily-accessible site
      for implantation and the provision of electrical stimulation. The present paper
      explores the efficacy of supra-choroidal electrical stimulation of retinal
      neurons. Based upon recordings made with surface electrodes placed on the primary
      visual cortex, areas of activation in the cortex were shown to change when
      different areas on the supra-choroidal space were stimulated. Finally, the
      threshold to elicit a response from neurons in the visual cortex, was found to be
      77.55 +/- 29.85 nC.

PMID- 19163029
TI  - Hearing aid gain prescriptions balance restoration of auditory nerve mean-rate
      and spike-timing representations of speech.
AB  - Linear and nonlinear amplification schemes for hearing aids have thus far been
      developed and evaluated based on perceptual criteria such as speech
      intelligibility, sound comfort, and loudness equalization. Finding amplification
      schemes that optimize all of these perceptual metrics has proven difficult. Using
      a physiological model, Bruce et al. [1] investigated the effects of single-band
      gain adjustments to linear amplification prescriptions. Optimal gain adjustments
      for model auditory-nerve fiber responses to speech sentences from the TIMIT
      database were dependent on whether the error metric included the spike timing
      information (i.e., a time-resolution of several microseconds) or the mean firing
      rates (i.e., a time-resolution of several milliseconds). Results showed that
      positive gain adjustments are required to optimize the mean firing rate
      responses, whereas negative gain adjustments tend to optimize spike timing
      information responses. In this paper we examine the results in more depth using a
      similar optimization scheme applied to a synthetic vowel /E/. It is found that
      negative gain adjustments (i.e., below the linear gain prescriptions) minimize
      the spread of synchrony and deviation of the phase response to vowel formants in
      responses containing spike-timing information. In contrast, positive gain
      adjustments (i.e., above the linear gain prescriptions) normalize the
      distribution of mean discharge rates in the auditory nerve responses. Thus,
      linear amplification prescriptions appear to find a balance between restoring the
      spike-timing and mean-rate information in auditory-nerve responses.

PMID- 19163030
TI  - Charge recovery during concurrent stimulation for a vision prosthesis.
AB  - Parallel or concurrent stimulation in an epiretinal neuroprosthesis is likely
      necessary in order to deliver sufficient phosphenes for effective vision.
      Important issues with concurrent stimulation are the effect of current
      distribution which introduces current leakage or 'cross talk' between adjacent
      electrodes and charge recovery which determines balanced charge being
      delivered/recovered at each electrode from the previous phase. In this paper, we
      present the effect of concurrent stimulation of two hexagonally arranged platinum
      electrode arrays on charge recovery. Balanced and imbalanced (unequal) currents
      were delivered to the hexagonal arrays when they were immersed in physiological
      saline. Both simulation and experimental results revealed that charge was not
      recovered at individual electrodes, particularly when imbalanced currents were
      delivered. However, total charge injected to both hexagonal arrays was recovered.

PMID- 19163031
TI  - DS-MAC: differential service medium access control design for wireless medical
      information systems.
AB  - The integration of wireless networking technologies with medical information
      systems (telemedicine) have a significant impact on healthcare services provided
      to our society. Applications of telemedicine range from personalized medicine to
      affordable healthcare for underserved population. Though wireless technologies
      and medical informatics are individually progressing rapidly, wireless networking
      for healthcare systems is still at a very premature stage. In this paper we first
      present our open architecture for medical information systems that integrates
      both wired and wireless networked data acquisition systems. We then present the
      implementation at the physical layer and differential service MAC design that
      adapts channel provisioning based on the information criticality. Performance
      evaluation using analytical modeling and simulation shows that our DS-MAC
      provides differentiated services for emergency, warning, and normal traffic.

PMID- 19163032
TI  - Implementing ISO/IEEE 11073: proposal of two different strategic approaches.
AB  - This paper explains the challenges encountered during the ISO/IEEE 11073 standard
      implementation process. The complexity of the standard and the consequent heavy
      requirements, which have not encouraged software engineers to adopt the standard.
      The developing complexity evaluation drives us to propose two possible
      implementation strategies that cover almost all possible use cases and eases
      handling the standard by non-expert users. The first one is focused on medical
      devices (MD) and proposes a low-memory and low-processor usage technique. It is
      based on message patterns that allow simple functions to generate ISO/IEEE 11073
      messages and to process them easily. In this way a framework for MDs can be
      obtained. Second one is focused on more powerful machines such as data loggers or
      gateways (aka. computer engines (CE)), which do not have the MDs' memory and
      processor usage constraints. For CEs a more intelligent and adaptative Plug&Play
      (P&P) solution is provided. It consists on a general platform that can access to
      any device supported by the standard. Combining both strategies will cut
      developing time for applications based on ISO/EEE 11073.

PMID- 19163033
TI  - Medical instrument data exchange.
AB  - Advances in medical devices and health care has been phenomenal during the recent
      years. Although medical device manufacturers have been improving their
      instruments, network connection of these instruments still rely on proprietary
      technologies. Even if the interface has been provided by the manufacturer (e.g.,
      RS-232, USB, or Ethernet coupled with a proprietary API), there is no widely
      accepted uniform data model to access data of various bedside instruments. There
      is a need for a common standard which allows for internetworking with the medical
      devices from different manufacturers. ISO/IEEE 11073 (X73) is a standard
      attempting to unify the interfaces of all medical devices. X73 defines a client
      access mechanism that would be implemented into the communication controllers
      (residing between an instrument and the network) in order to access/network
      patient data. On the other hand, MediCAN technology suite has been demonstrated
      with various medical instruments to achieve interfacing and networking with a
      similar goal in its open standardization approach. However, it provides a more
      generic definition for medical data to achieve flexibility for networking and
      client access mechanisms. In this paper, a comparison between the data model of
      X73 and MediCAN will be presented to encourage interoperability demonstrations of
      medical instruments.

PMID- 19163034
TI  - Optimization proposal of a standard-based patient monitoring platform for
      ubiquitous environments.
AB  - This article describes the optimization of a patient telemonitoring platform
      based on the ISO/IEEE11073 (X73) standard to enable medical device
      interoperability. In order to achieve this, principal advantages and remaining
      improvements are evaluated to include in further upgrades towards the new profile
      evolution, oriented to ubiquitous environments and wearable devices (Personal
      Health Devices, X73-PHD), and opened to additional plug-and-play features and
      remote management. After evaluating the possibilities, we describe the platform
      porting process, a required step to adapt it to the new functionalities and
      allowing the development of end-to-end standard based systems. The paper details
      the implementation of the agent-manager architecture, particularized on the X73
      PHD communication protocol between a Medical Device (MD) and a central gateway
      (Compute Engine, CE). Lastly, the obtained results are evaluated, oriented to
      constitute an X73-PHD tester to prove the challenges currently under discussion
      in the European Standardization Committee (CEN).

PMID- 19163035
TI  - Mechanisms of security based on digital certificates applied in a telemedicine
      network.
AB  - The medical patient's information is private and extremely sensitive. This
      information has to be stored and transmitted carefully because it can be exposed
      to a series of threats and it is necessary to be protected. This research
      contemplates the security mechanisms based on digital certificates applied to a
      pilot telemedicine network, that guarantees the confidentiality, integrity and
      availability of the medical information of the patients for the hospitable
      centers involved. The prototype telemedicine network will interconnect hospitals
      in the municipalities of Baruta and Hatillo Miranda State, in Venezuela by
      Internet, to provide and support a health care system in inaccessible areas, and
      the transmission of patient's biomedical signals and the health education to
      people through secure mechanisms such as digital certificates.

PMID- 19163036
TI  - SLIM: a Secured Lightweight Interactive Middleware for wireless body area
      network.
AB  - Advances in wireless sensor technology have introduced a new dimension in
      healthcare computing. With miniaturized sensor devices, continuous medical
      monitoring of patients to detect transient life threatening conditions from daily
      activities has been made possible. This phenomenon will certainly improve the
      quality of life for a majority of people. However, the growing variety of sensor
      devices in the market, has made application developments very challenging. In
      light of this view, we are proposing SLIM, a lightweight middleware that shields
      the underlying differences in sensor technology from the application layer. SLIM
      is designed to simplify/accelerate application development while not simply
      providing common middleware functions (i.e. data acquisition and plug-and-play
      capability) but also others like security and interactive features. To support
      both indoor and outdoor activities, SLIM is built to reside on mobile devices. At
      the end of the paper, we will show the prototype of the proposed middleware
      including its functionalities when used with a mobile application.

PMID- 19163037
TI  - Biomaterials for spinal cord regeneration: outgrowth of presumptive neuronal
      precursors on electrospun poly(epsilon)-caprolactone scaffolds microlayered with
      alternating polyelectrolytes.
AB  - The aim of this study was to assess the feasibility of electrospun poly(epsilon)
      caprolactone (PCL) scaffolds treated with alternating paly-electrolytes as a
      controllable three-dimensional adhesive substrate for neuronal progenitors.
      Unmodified PCL surfaces were generally not supportive of mouse embryonic stem
      cell (mESC) colony adhesion. However, scaffolds surfaced using layer-by-layer
      (LbL) deposition of heparin/poly-L-lysine encouraged better local adhesion of
      mESC colonies, and networking of monolayers containing nestin-positive
      presumptive neurons, similar to laminin coated controls, as observed by immuno
      fluorescence microscopy. Confocal microscopy further revealed depth-wise
      penetration of mESC nestin-positive cell populations, and orientation along grass
      topographical features in the LbL scaffolds. LbL deposition therefore appears to
      provide a satisfactory adhesive substrate for contact and mechanical guidance of
      neuronal outgrowth in three-dimensions.

PMID- 19163038
TI  - Effect of connector width on stress distribution in all ceramic fixed partial
      dentures (a 3D finite element study).
AB  - STATEMENT OF PROBLEM: Connectors in fixed partial dentures (FPDs) are the weakest
      areas and responsible for failure in most cases. Optimizing the design of
      connectors will lead to higher strength and better performance of all-ceramic
      FPDs. PURPOSE OF STUDY: The aim of this study was to use the finite element
      method in order to simulate the effect of connector width on stress distribution
      in all-ceramic FPDs. MATERIAL AND METHODS: Three 3-dimensional finite element
      models for a 3-unit FPD made of IPS-Empress 2 representing a lower first molar
      were created and a static load of 500 N was applied axially at mid pontic area.
      By choosing three different widths, 3 mm, 4 mm, 5 mm for connectors, three models
      I,II, and III for complete assembly of teeth and connectors were created.
      RESULTS: Maximum stress occurred in the connector area in all models. Compared to
      model I, stress decreased 24% in model III; so the wider connector lead to lower
      stress values. CONCLUSION: Connectors are the most regular area for the fracture
      in all-ceramic FPDs because of high concentration of stress. Decreasing the width
      of connector raises the stress and increases the risk for fracture. Also, maximum
      stress in bridges is less than half of the strength of IPS-Empress2 and no
      failure is expected for all cases. CLINICAL IMPLICATIONS: This in vitro study of
      3-unit all ceramicFPDs made with IPS-Empress2 shows that an increase in the width
      of connector reduces the stress concentration and improves the likelihood of long
      term prognosis. Also, IPS-Empress2 can be used in posterior regions in many
      cases.

PMID- 19163039
TI  - Peptide-functionalized microfabricated structures for improved on-chip neuronal
      adhesion.
AB  - Extracellular, high signal-to-noise ratio recordings from electrogenic cells
      require a tight coupling between the cellular membrane and the recording
      electrode. Self assembled monolayers (SAMs) of alkanethiols functionalized with
      peptides were used in combination with micro- and nano-structured features on the
      sensor surface. This combination of surface chemistry and topography triggers a
      phagocytosis-like engulfment and ensures tight coupling. In this paper we report
      the results concerning usage of different SAMs and the influence of the peptide
      concentration towards cell adhesion and outgrowth. Later on, the optimized
      peptide functionalized SAMs were applied on micro- and nano-structured sensor
      surfaces. As a result, phagocytosis-like events could be shown using focused ion
      beam SEM and confocal fluorescence imaging.

PMID- 19163040
TI  - Characterization of proteolytically digested zebrafish chorion as extracellular
      matrix.
AB  - Extracellular matrix (ECM) plays pivotal roles in developments, wound healing,
      migration, angiogenesis, and other tissue developments. Developing new ECM may
      give us an innovative approach of controlling the cell and tissue behavior,
      regenerating damaged tissues, and other biotechnology usages. Here we report new
      ECM like biomaterials, pFZC, obtained from the fertilized Zebrafish chorion
      (FZC). pFZC was prepared by digesting the fertilized Zebrafish chorion with
      pronase. Differentiation of P19 embryonic carcinoma cells (P19 EC) on pFZC
      demonstrated that the level of the differentiation of P19 EC was comparable to
      cells on gelatin or fibronectin coated cover slide. Analyses of glycosylations of
      Zebrafish chorions using various Lectins revealed that during the fertilization,
      structurally organized glycosylations of Zebrafish chorion were increased and FZC
      was glycosylated with mannose, fucose, n-acetylglucosamine, and sialic acid. In
      addition, after FZC proteolytic digestion with pronase, the digested FZC
      proteins, pFZC, displayed similar glycosylation manner. SDS gel electrophoresis
      and mass spectroscopy analysis of pFZC revealed that the major component of pFZC
      is ZP2 protein. Newly identified ECM like biomaterials, pFZC, will provide more
      broad ways of controlling the cell and tissue environments.

PMID- 19163041
TI  - Cytotoxic analysis of the conducting polymer PEDOT using myocytes.
AB  - Biosensors interact with biological systems at the surface of the sensor. Coating
      these sensors with electrically active polymers has been suggested to improve
      this interface. The electrically conducting polymer poly (3, 4
      ethylenedioxythiophene) (PEDOT) enhances electrical recordings by improving
      conductivity while maintaining chemical stability. It also offers great
      flexibility in studying cell substrate interactions because of the variety of
      counter-ions that can be incorporated into the PEDOT matrix. To provide any true
      benefit in cell culture or in vivo experiments, the cytotoxicity of PEDOT must
      first be determined. This study evaluated the cytotoxicity of PEDOT doped with
      either polystyrene sulfonate (PSS) or phosphate buffered saline (PBS) ions and
      tested the efficacy of using the conductive PEDOT substrates for myoblast
      proliferation and differentiation. Results show that PEDOT/PBS and PEDOT/PSS are
      not cytotoxic to cells and successfully support cellular proliferation and
      differentiation. These results establish PEDOT as a material for cell-substrate
      interface studies. With biosensors being modified using the new polymer coating
      PEDOT, this cytotoxicity study provides evidence that PEDOT coatings will not
      induce a cytotoxic response when implanted in vivo.

PMID- 19163042
TI  - Mechanical characterization of polymeric microcapsules using a force-feedback
      MEMS microgripper.
AB  - This paper reports a monolithic, force-feedback MEMS (microelectomechanical
      systems) microgripper and its application to micro-scale compression testing of
      swollen hydrogel microcapsules during manipulation in an aqueous environment. The
      single-chip microgripper uses an electrothermal microactuator for grasping and
      integrates two capacitive force sensors, one for contact detection (force
      resolution: 38.5nN) and the other for gripping force measurements (force
      resolution: 19.9nN). Using the force-feedback microgripper and a mechanics model
      for assessing large deformation data, the system with a 19.9nN force resolution
      and a 20.5nm resolution for material deformation measurement quantified Young's
      modulus values of individual alginate microcapsules (15-25microm) with 1%, 2%,
      and 3% chitosan coating, demonstrating an easy-to-operate, accurate compression
      testing technique for mechanically characterizing soft, micrometer-sized
      biomaterials.

PMID- 19163044
TI  - Fiber-optic endomicroscopy system for high-resolution nonlinear imaging of
      biological tissue.
AB  - A flexible fiber-optic endomicroscopy system was developed for nonlinear optical
      imaging of biological samples. Double-clad fiber and photonic bandgap fiber were
      employed in the endomicroscope for femtosecond pulse delivery, dispersion
      compensation, nonlinear optical signals collection and fast beam scanning. Three
      dimensional imaging of biological tissues based on second harmonic generation and
      two-photon excited fluorescence was performed with the endomicroscope. The depth
      resolved imaging results strongly suggest the potential of this flexible fiber
      optic microscope system for real-time assessment of both epithelial and stromal
      structures in luminal organs.

PMID- 19163043
TI  - Combining field imaging endoscopy with point analysis spectroscopy for improving
      early lung cancer detection.
AB  - We propose to combine field imaging endoscopy with point spectral analysis for
      improving the overall diagnostic accuracy in clinical lung cancer detection. For
      this purpose, we developed an integrated endoscopy system that uses
      autofluorescence imaging and white light reflectance imaging to obtain high
      diagnostic sensitivity, while at the same time uses non-contact point
      reflectance/fluorescence spectroscopy to reduce false positive biopsies, thus,
      achieve high diagnostic specificity. A pilot clinical test on 22 lung patients
      demonstrated that using this system the malignant lung lesions can be
      differentiated from the benign lesions with both diagnostic sensitivity and
      specificity of better than 80%. To further reduce the number of false positive
      diagnosis and allow even higher diagnostic accuracies, we have also developed an
      endoscopic laser Raman probe for in vivo real-time biochemical analysis of the
      suspicious tissue areas identified by the field imaging modalities (white light
      imaging and autofluorescence imaging). Preliminary Raman spectroscopy results
      will be reported at the conference.

PMID- 19163046
TI  - Multi-angle LUCAS for high-throughput on-chip cytometry.
AB  - We illustrate that by recording under-sampled diffraction patterns of cells at
      different illumination angles, we can achieve high-throughput on-chip
      characterization of a heterogeneous cell solution over an ultra large volume of
      approximately 5 ml. This platform, termed multi-angle LUCAS, is especially
      promising for cost-effective point-of-care cell counting applications.

PMID- 19163047
TI  - Impedimetric microanalysis system for deep vein thrombosis point-of-care testing.

PMID- 19163048
TI  - The NeuroProbes project: a concept for electronic depth control.
AB  - The European project NeuroProbes has introduced a new methodology to allow the
      fine positioning of electrodes within an implantable probe with respect to
      individual neurons. In this approach, probes are built with a very large number
      of electrodes which are electronically selectable. This feature is implemented
      thanks to the modular approach adopted in NeuroProbes, which will allow the
      implementation of integrated electronics both along the probe shaft and on the
      array backbone.

PMID- 19163049
TI  - Bio-sensing textiles to support health management.

PMID- 19163050
TI  - Modulation filtering for heart and lung sound separation from breath sound
      recordings.
AB  - Separation of heart and lung sounds from breath sound recordings is a challenging
      task due to the temporal and spectral overlap of the two signals. In this paper,
      the use of a spectro-temporal representation to improve signal separation is
      investigated. The representation is obtained by means of a frequency
      decomposition (termed modulation frequency) of temporal trajectories of short
      term spectral components. Experiments described herein suggest that improved
      separability of heart (HS) and lung sounds (LS) is attained in the modulation
      frequency domain. Bandpass and bandstop modulation filters are designed to
      separate HS and LS signals from breath sound recordings, respectively. Visual and
      auditory inspection, quantitative analysis, as well as algorithm execution time
      are used to assess algorithm performance. Log-spectral distances below 1 dB
      corroborate our listening test which found no audible artifacts in separated
      heart and lung sound signals.

PMID- 19163051
TI  - Eigenvector analysis for separation of a spectrally concentrated source from a
      mixture.
AB  - An objective function is presented to recover a spectrally narrow band signal
      from multichannel measurements, as in electrocardiogram recordings of atrial
      fibrillation. The criterion can be efficiently maximized through the eigenvalue
      decomposition of some spectral correlation matrices of the whitened observations
      across appropriately chosen frequency bands. It is conjectured that the global
      optimum so attained recovers the source of interest when its spectral
      concentration around its modal frequency is maximal. Numerical experiments on
      synthetic data seem to support the validity of this hypothesis. Moreover, the
      components extracted from a patient data set with known atrial fibrillation show
      the characteristics of the associated f-wave as described in medical literature.

PMID- 19163052
TI  - The exploitation of spatial topographies for atrial signal extraction in atrial
      fibrillation ECGs.
AB  - The accuracy in the extraction of the atrial activity (AA) from electrocardiogram
      (ECG) signals recorded during atrial fibrillation (AF) episodes plays an
      important role in the analysis and characterization of atrial arrhythmias. The
      present contribution puts forward a method for AA signal extraction based on a
      blind source separation (BSS) formulation. The latter exploits spatial
      information on the different components in the ECG related or not to AF. The
      source directions or spatial topographies of the components not related to AF are
      used to determine the nullspace of the AA, so that the topographies related to AA
      become more suitable to describe AF sources. The comparative performance of the
      method is evaluated on real data recorded from patients with noticeable AF. The
      AA extraction quality of the proposed technique is comparable to that of previous
      algorithms.

PMID- 19163053
TI  - Noninvasive detection of small bowel electrical activity from SQUID magnetometer
      measurements using SOBI.
AB  - We report a robust method for noninvasive biomagnetic detection of small bowel
      electrical activity. Simultaneous Superconducting QUantum Interference Device
      (SQUID) magnetometer (MENG) and serosal electrode recordings were made on pig
      small bowel. The SOBI blind-source separation algorithm was used to separate the
      underlying source signals of the MENG. Comparison of identified SOBI components
      to the serosal recordings validated the underlying MENG sources as being enteric
      in origin. Non-invasive detection of small bowel electrical activity could have
      significant implications in a clinical setting.

PMID- 19163054
TI  - Robustness of the blind source separation with reference against uncertainties of
      the reference signals.
AB  - The fetal electrocardiogram (ECG) could provide clinical information concerning
      physiological conditions of the fetus. In order to extract fetal ECG, we proposed
      the novel algorithm, the blind source separation with reference (BSSR), which
      successfully extracts a complete waveform of QRS complex and avoids uncertainty
      in the order of the extracted signals. In the BSSR, the reference signal is
      supposed to be generated from the ultrasonic Doppler signal. Thus generated
      reference is expected to suffer from uncertainties in waveform and occurrence
      timing. Based on simulations, the BSSR is shown to have robustness against the
      uncertainties of reference signals. In addition, it is shown how the robustness
      depends on the order of power of correlation function between the reference and
      extracted signals, which composes a performance function of the BSSR.

PMID- 19163055
TI  - ICA based multiple brain sources localization.
AB  - In this paper we describe an Independent Component Analysis (ICA) method for
      computing the brain signals of unknown source parameters for the inverse problem.
      First, a method is applied to estimate the number of dipoles beforehand and
      reduce dimensionality which can reduce the ICA complexity and improve the
      unmixing accuracy. We apply Blind Source Separation (BSS) for separating
      multichannel EEG evoked by multiple dipoles into temporally independent
      stationary sources. For every independent source, we are able to determine the
      electrode potentials evoked by every dipole separately by the projection of
      independent activation maps back onto the electrode arrays. Then for every set of
      electrode potentials, a source localization procedure is performed which only
      involves searching for one dipole, thus dramatically reducing the search
      complexity. In the paper, it is explored that the possibility of applying ICA for
      EEG multiple dipoles localization when the data are corrupted by additive noise.
      Furthermore, we also give the relationship of unmixing accuracy, distance between
      dipoles and dipoles moment movements.

PMID- 19163056
TI  - A novel approach for Doppler blood flow measurement.
AB  - A new approach to frequency estimation for the velocity estimation in Doppler
      ultrasound blood flow analysis is presented. The basis of the approach is an
      adaptive sinusoid-tracking algorithm which is effective in extracting
      nonstationary signals from within noise and estimating their time-varying
      parameters, such as the frequency, over time. The preliminary studies conducted
      using simulated signals show the potential of this approach in estimating Doppler
      frequency shifts under noisy conditions. A qualitative comparison with the short
      time Fourier transform (STFT) is presented to show the advantages of the proposed
      technique over the STFT. The proposed approach offers advantages over
      conventional time-frequency analysis techniques in terms of high time-frequency
      resolution and high noise immunity.

PMID- 19163057
TI  - Non-invasive measurement of respiratory rate in children using the
      photoplethysmogram.
AB  - Respiratory rate is recognised as a valuable predictor of the severity of illness
      in children, but it is not currently feasible to measure this automatically in a
      triage environment. Autoregressive modelling on data from the pulse oximeter
      photoplethysmogram has the potential to introduce automated breathing measurement
      into the realm of paediatric triage. Using autoregressive modelling, it is shown
      that respiratory rate can be extracted from the paediatric photoplethysmogram
      with a mean error of 3.4 breaths per minute.

PMID- 19163058
TI  - Automatic wheeze detection using histograms of sample entropy.
AB  - In this paper, we propose a robust and automatic wheeze detection method using
      sample entropy (SampEn) histograms of the filtered narrow band respiratory sound
      signals. The sound signals are segmented first into their respective
      inspiration/expiration phases. Time-frequency distribution of each segment is
      then obtained using Gabor spectrogram. After the construction of SampEn plane,
      histograms of the selected frequency bins of the SampEn plane are calculated. The
      mean distortion of the histograms are used as discriminating features for segment
      wise wheeze detection. Detection experiments are carried out irrespective of
      inspiration/expiration segments of the respiration sound signals recorded and
      preprocessed under different conditions, and the overall wheeze detection
      accuracy is 97.9% for high intensity wheezes during expirations and is up to
      85.3% for low intensity wheezes occurring in inspirations.

PMID- 19163059
TI  - Crackles detection using a time-variant autoregressive model.
AB  - Several techniques have been explored to detect automatically fine and coarse
      crackles; however, the solution for automatic detection of crackles remains
      insufficient. The purpose of this work was to explore the capacity of the time
      variant autoregressive (TVAR) model to detect and to provide an estimate number
      of fine and coarse crackles in lung sounds. Thus, simulated crackles inserted in
      normal lung sounds and real lung sounds containing adventitious sounds were
      processed with TVAR and by an expert that based crackle detection on time
      expanded waveform-analysis. The coefficients of the TVAR were obtained by an
      adaptive filtering prediction scheme. The adaptive filter used the recursive
      least squares algorithm with a forgetting factor of 0.97 and the model order was
      four. TVAR model showed an efficiency to detect crackles over 90% even with
      crackles overlapping and amplitudes as low as 1.5 of the standard deviation of
      background lung sounds, where expert presented an efficiency around 30%. In
      conclusion, TVAR model is a proper alternative to detect and to provide an
      estimate number of fine and coarse crackles, even in presence of crackles
      overlapping and crackles with low amplitude, conditions where crackles detection
      based on time-expanded waveform-analysis reveals evident limitations.

PMID- 19163060
TI  - High-resolution analysis of transient evoked otoacoustic emissions.
AB  - A new decomposition and time-frequency method applied to the estimation of
      transient evoked otoacoustic emissions (TEOAEs) is presented. TEOAEs are low
      level signals in response to auditory stimuli that are used to monitor the
      functionality of the cochlea. TEOAE parameter estimation is challenging due to
      the short duration of the signal (about 20ms) and its highly nonstationary
      nature. Existing time-frequency methods are incapable of providing accurate
      estimates of the components within the TEOAE signal. The proposed decomposition
      and time-frequency method is based on the effective tracking of nonstationary
      sinusoidal components using a nonlinear iterative sinusoid tracking algorithm.
      The presented technique improves upon existing techniques by offering a high time
      frequency resolution and is capable of providing accurate estimates of components
      within a TEOAE signal. The structure of the proposed decomposition technique as
      well as the underlying algorithm are presented. Simulation results are presented
      to show the performance of the proposed technique. Its performance is also
      demonstrated on a clinically recorded signal.

PMID- 19163061
TI  - Peri-event cross-correlation over time for analysis of interactions in neuronal
      firing.
AB  - Several methods have been described in the literature to verify the presence of
      couplings between neurons in the brain. In this paper we introduce the peri-event
      cross-correlation over time (PECCOT) to describe the interaction among the two
      neurons as a function of the event onset. Instead of averaging over time, the
      PECCOT averages the cross-correlation over instances of the event. As a
      consequence, the PECCOT is able to characterize with high temporal resolution the
      interactions over time among neurons. To illustrate the method, the PECCOT is
      applied to a simulated dataset and for analysis of synchrony in recordings of a
      rat performing a go/no go behavioral lever press task. We verify the presence of
      synchrony before the lever press time and its suppression afterwards.

PMID- 19163062
TI  - Simple quantification of multiplexed quantum dot staining in clinical tissue
      samples.
AB  - In this paper, we present a simple method for the processing and quantification
      of multiplexed Quantum Dot (QD) labeled images of clinical cancer tissue samples.
      QDs provide several features which make them ideal for reliable quantification,
      including long-term signal stability, high signal-to-noise ratios, as well as
      narrow emission bandwidths. Deconvolution of QD spectra is accomplished in a
      batch mode in which unmixing parameters are preserved across samples to allow for
      quantitative and reproducible comparisons. After unmixing the QD images, we
      segment each one to exclude acellular regions. We use a simple average intensity
      to quantify the level of QD staining for each image. We illustrate the viability
      of this approach by testing it on 28 tissue samples using a tissue microarray. We
      show that using as few as two QD protein targets (MDM-2, and B-actin), the Renal
      Cell Carcinoma (RCC) samples are distinguishable from adjacent normal tissue
      samples. A simple linear discriminant results in 100% classification of 25 RCC
      samples and 3 normal samples. This suggests that multiplexed QDs can be used to
      properly diagnose RCC from otherwise healthy tissue. We expect to apply this work
      to larger panels of more robust QD biomarker targets to aid in clinical decision
      making for the diagnosis and prognosis of diseases, such as cancer.

PMID- 19163063
TI  - Automatic classification of chromosomes in Q-band images.
AB  - The manual analysis of the karyogram is a complex, wearing and time-consuming
      operation. It requires a very meticulous attention to details and calls for well
      trained personnel. Even though existing commercial software packages provide a
      reasonable support to cytogenetists, they very often require human intervention
      to correct challenging situations. We developed a robust automatic classification
      system conceived to cope with routine images in which chromosomes are randomly
      rotated, possibly blurred or also corrupted by overlapping or by dye stains. It
      consists in a sequence of modules comprising robust feature extraction based on
      medial axis, chromosome polarization, feature pre-processing, and Neural Network
      classification followed by a class reassigning algorithm.We show the
      effectiveness of the proposed method on data comprising karyotypes belonging to
      slightly different stage of the prometaphase. This dataset contains 119
      karyotypes (5474 chromosomes), 70 of which were used for training and validation
      and 49 for the final testing. In this latter set of images, the system achieved a
      classification accuracy, as compared to manual ground truth, of 95.6%.

PMID- 19163064
TI  - Gesture recognition for interactive exercise programs.
AB  - This paper describes a gesture recognition system which can recognize seated
      exercises that will be incorporated into an in-home automated interactive
      exercise program. Hidden Markov Models (HMMs) are used as a motion classifier,
      with motion features extracted from the grayscale images and the location of the
      subject's head estimated at initialization. An overall recognition rate of 94.1%
      is achieved.

PMID- 19163065
TI  - Automatic chromosome pairing using mutual information.
AB  - Cytogenetics is a key tool in the detection of acquired chromosomal abnormalities
      and in the diagnosis of genetic diseases such as leukemia. The karyotyping is a
      set of procedures, in the scope of the cytogenetics, that produces a visual
      representation of the 46 chromosomes (called karyogram), paired and arranged in
      decreasing order of size. The pairing procedure aims to identify all pairs of
      homologous chromosomes.The pairing criterion is based on dimensional,
      morphological,and textural features similarity. This process is time consuming
      when performed manually, and demanding from a technical point of view. An
      automatic pairing algorithm would thus bring benefits, but it remains an open
      problem to date.In this paper a new strategy for automatic pairing of homologous
      chromosomes is proposed. Besides the traditional features described in the
      literature, the Mutual Information (MI) is used to discriminate chromosome
      textural differences. A supervised non-linear classifier is trained by using
      manual classifications provided by expert technicians, combining the different
      features computed from each pair.Simulations using 836 real chromosome images,
      obtained with a Leica Optical Microscope DM 2500, in a leave-one-out cross
      validation fashion, were performed for training and testing the
      algorithm.Promising and relevant results were found, despite the poor quality of
      the original chromosome images, contrasting with state-of the-art algorithms and
      datasets found in the literature.

PMID- 19163066
TI  - A vectorial image classification method based on neighborhood weighted Gaussian
      mixture model.
AB  - The CT uroscan contains three to four time-spaced acquisitions of the same
      patient. Registration of these acquisitions forms a vectorial volume, which
      contains a more complete anatomical information. In order to outline the
      anatomical structures, multi-dimensional classification is necessary for
      analyzing this vectorial volume. Because of the partial volume effect (PVE),
      probability distributions are assigned to the different material types within
      this vectorial volume instead of a definite material distribution. Gaussian
      mixture model is often used in probability classification problems to model such
      distributions, but it relies only on the intensity distributions, which will lead
      a misclassification on the boundaries and inhomogeneous regions with noises. In
      order to solve this problem, a neighborhood weighted Gaussian mixture model is
      proposed in this paper. Expectation Maximization algorithm is used as
      optimization method. The experiments demonstrate that the proposed method can get
      a better classification result and less affected by the noise.

PMID- 19163067
TI  - Leveraging genetic algorithm and neural network in automated protein crystal
      recognition.
AB  - We propose a classification framework combined with a multi-scale image
      processing method for recognizing protein crystals in high-throughput images. The
      main three points of the processing method are the multiple population genetic
      algorithm for region of interest detection, multi-scale Laplacian pyramid filters
      and histogram analysis techniques to find an effective feature vector. Using
      human (expert crystallographers) classified images as ground truth, the current
      experimental results gave 88% true positive and 99% true negative rates,
      resulting in an average true performance of approximately 93.5% validated on an
      image database which contained over 79,000 images.

PMID- 19163068
TI  - A tactile feedback system for robotic surgery.
AB  - A tactile feedback system was developed and mounted on the da Vinci robotic
      surgical system. The system features silicone-based tactile balloon actuators
      mounted on the robotic master controls, modified commercial piezoresistive
      sensors mounted on the robotic end effectors, and a pneumatic control system. The
      system has a frequency response of up to 20 Hz, a linear input force-output
      pressure relationship, and provides five discrete levels of actuation over a
      force input range of 0 to 25 N. A demonstration of the system with four subjects
      grasping a phantom with an embedded pressure-sensitive film suggested that less
      force was applied with tactile feedback. This paper describes the design,
      fabrication, characterization, and demonstration of the mounted tactile feedback
      system and its components. Ongoing studies using the system will assess the
      benefit of tactile stimuli to learning and control in robotic surgery.

PMID- 19163069
TI  - Development of a microsurgery training system.
AB  - Surgeons require significant training to acquire sufficient dexterity and hand
      eye coordination to manipulate objects skillfully under the microscope. This
      paper presents a computer-based real-time simulation of microsurgery as well as
      the hardware setup. It presents a realistic physics-based elastic suture and
      blood vessel model, fast collision detection techniques, suture insertion process
      and novel approach of a haptic forceps. The simulation environment demonstrates a
      complete vascular suturing system to train skills such as grasping, suture
      placement, needle insertion and knot-tying running at 500 Hz, sufficient for
      physical realism.

PMID- 19163070
TI  - Enhancement of kinesthetic perception for microsurgical teleoperation using
      impedance-shaping.
AB  - A new control scheme is developed in this paper for a bilateral teleoperation
      system for microsurgical applications. The main objective of the proposed control
      scheme is to enhance the kinesthetic perception of the operator. First, the
      kinesthetic perception, based on psychophysics, is classified into three metrics
      of detection, sensitivity of detection, and discrimination. Additionally, a new
      performance index is introduced as a combination of these three metrics to
      quantify the kinesthetic performance. Second, modified macro-micro bilateral
      control system using an impedance-shaping method is proposed. The proposed
      controller can increase kinesthetic perception by shaping and magnifying the
      transmitted impedance to the operator. Finally, the performance of the proposed
      controller is verified in a comparison with the two-channel position-position
      (PP) controller, the two-channel force-position (FP) controller, and the four
      channel transparency- optimized controller.

PMID- 19163071
TI  - Lower bounds on the optimal control of soft tissue grasping.
AB  - The interaction between surgical tools and soft tissue has nonlinear mechanical
      properties. In robot-assisted surgery, a pre-specified trajectory of tool
      positions (or applied forces) is desired for achieving a surgical treatment. Due
      to the computational complexity involved in solving the nonlinear optimal
      trajectory following problem, a tractable path is to find lower bounds on the
      optimal cost. The lower bound serves as a reference to evaluate the goodness of
      any specific controller. A mathematical derivation of a lower bound on the
      optimal cost of the dynamic optimization problem, using a linear matrix
      inequality (LMI) approach, is developed. Semi-definite programming is used to
      solve the LMIs. This approach is demonstrated for a previously studied soft
      tissue grasping control problem.

PMID- 19163072
TI  - Autoregressive nodeling of physiological tremor under microsurgical conditions.
AB  - Tremor was recorded under simulated vitreoretinal microsurgical conditions as
      subjects attempted to hold an instrument motionless. Several autoregressive
      models (AR, ARMA, multivariate, and nonlinear) are generated to predict the next
      value of tremor. It is shown that a sixth order ARMA model predictor can predict
      a tremor having an amplitude of 96.6 +/- 84.5 microns RMS with an error of 8.2 +/
      5.9 microns RMS, a mean improvement of 47.5% over simple last-value prediction.

PMID- 19163073
TI  - A study of a hand-held instrument's angular motion due to physiological tremor in
      micromanipulation tasks.
AB  - Angular motion of a hand-held instrument due to physiological tremor during
      micromanipulation tasks was recorded with a six degree-of-freedom accelerometer
      based sensing unit placed in the instrument. Methods to get angular velocities
      and angular accelerations from the acceleration readings of accelerators in the
      sensing unit are described. Statistics of angular velocity and angular
      acceleration of the instrument due to the tremor obtained from ten normal
      subjects are reported. Assumption of very small tremor angular velocities in
      micromanipulation tasks to calculate tremor angular accelerations analytically is
      validated.

PMID- 19163074
TI  - User evaluation of a collaborative wheelchair system.
AB  - The collaborative wheelchair assistant (CWA) is a robotic wheelchair which makes
      full use of human skills, by involving the user into the navigation control. The
      user gives the high-level commands and directly controls the speed, while the low
      level control is taken over by the machine, which constrains the wheelchair to
      follow a software defined guide path. This paper presents an evaluation of the
      CWA system, consisting of experiments performed with human subjects including
      three people with cerebral palsy (CP) and two with traumatic brain injury (TBI).
      We investigate the performance of the system in terms of its interaction with
      human subjects and motion efficiency and compare to that of able-bodied subjects,
      who have previously performed the same evaluation. The results suggest that the
      CWA brings safe motion and drastically simplifies the control without
      compromising the navigation performance.

PMID- 19163075
TI  - Muscle coordination in healthy subjects during floor walking and stair climbing
      in robot assisted gait training.
AB  - The aim of gait rehabilitation is a restoration of an independent gait and
      improvement of daily life walking functions. Therefore the specific patterns,
      that are to be relearned, must be practiced to stimulate the learning process of
      the central nervous system (CNS). The Walking Simulator HapticWalker allows for
      the training of arbitrary gait trajectories of daily life. To evaluate the
      quality of the training a total of 9 subjects were investigated during free floor
      walking and stair climbing and during the same tasks in two different training
      modes on the HapticWalker: 1) with and 2) without vertical center of mass (CoM)
      motion. Electromyograms (EMG) of 8 gait relevant muscles were measured and muscle
      activation was compared for the various training modes. Besides the muscle
      activation as an indicator for the quality of rehabilitation training the study
      investigates if a cancellation of the vertical CoM movement by adaption of the
      footplate trajectory is feasible i.e. the muscle activation patterns for the two
      training modes on the HapticWalker agree. Results show no significant differences
      in activation timing between the training modes. This indicates the feasibility
      of using a passive patient suspension and emulate the vertical CoM motion by
      trajectory adaption of the footplates. The muscle activation timing during
      HapticWalker training shows important characteristics observed in physiological
      free walking though a few differences can still remain.

PMID- 19163076
TI  - Is the collaborative wheelchair adapted to cerebral palsy and traumatic brain
      injury subjects?
AB  - The collaborative wheelchair assistant (CWA) provides guidance along software
      defined paths while the user is in charge of the speed control, including start
      and stop. Three patients with Cerebral Palsy (CP) and two with Traumatic Brain
      Injury (TBI), who had been ruled out for independent mobility, performed
      experiments with the CWA. While initially no subject was able to move
      independently, all subjects learned to drive with the CWA in a few sessions. Two
      subjects became able to drive a normal powered wheelchair. The other three could
      use the mobility provided by the CWA, while two of them could also use the tools
      to modify the guide paths. This suggests that the CWA is useful for a range of
      people with different disabilities.

PMID- 19163077
TI  - Body weight support by virtual model control of an impedance controlled
      exoskeleton (LOPES) for gait training.
AB  - The feasibility of an alternative method to support body weight in a powered
      exoskeleton is demonstrated. Instead of using an overhead suspension system, body
      weight is supported by augmenting the joint moments through virtual model
      control. The advantages of this novel method is that it allows for independent
      support of the left and right leg, and does not interfere with the excitation of
      cutanous afferents and balance of the body or trunk. Results show that after a
      short familiarization period the activity of muscles during initial stance
      reduces and kinematics become close to normal.

PMID- 19163078
TI  - 'Hybrid-PLEMO', rehabilitation system for upper limbs with active / passive force
      feedback mode.
AB  - Several rehabilitation robots for upper limbs have been proposed so far, and
      clinical effectiveness was reported in several studies for the aged people or
      patients with stroke. However most of them have only 2-DOF for its active motion.
      It is important for designing a rehabilitation system which trains in the 3-DOF
      space because the upper limbs of humans works in 3-DOF space even expect for the
      wrist. We developed the quasi 3-DOF rehabilitation system which has 2-DOF force
      feedback function in working plane but its working plane can be adjusted the
      inclination. And we named it Hybrid-PLEMO for it can be switched between active
      type and passive type. Hybrid-PLEMO is a compact, low-cost rehabilitation system
      for upper limbs with high safety by using ER brakes or ER actuators.
      Additionally, in Hybrid-PLEMO, we take direct-drive linkage mechanism by adding
      sub links. In this paper, we describe the mechanism and haptic control of Hybrid
      PLEMO.

PMID- 19163079
TI  - Assessment of walking performance in robot-assisted gait training: a novel
      approach based on empirical data.
AB  - Motivation and voluntary drive of patients can be improved by applying
      biofeedback during robot-assisted rehabilitation trainings. Biofeedback systems
      were traditionally based on theoretical assumptions. In this paper, we present a
      novel approach to calculate biofeedback during robot-assisted gait training. Our
      method was based on empirical data that were obtained from healthy subjects when
      simulating distinctive degrees of walking performance during robot-assisted gait
      training. This empirical data-based biofeedback (EDBF) method was evaluated with
      18 subjects without gait disorders. A higher correlation between the subjects'
      walking performance and biofeedback values was found for the EDBF method compared
      to a theory-based biofeedback approach.

PMID- 19163080
TI  - Modification of autonomic balance by electrical acupuncture does not affect
      baroreflex dynamic characteristics.
AB  - BACKGROUND: We have demonstrated that modification of autonomic balance by
      electrical vagal stimulation delays progression of cardiac dysfunction and
      cardiac remodeling, and prolongs survival in rats with severe heart failure. We
      have also shown that we were able to modify autonomic balance by electrical
      acupuncture at the acupoint of Zusanli, potentially applicable for the treatment
      of heart failure. We examined the effect of the acupuncture on the dynamic
      characteristics of the baroreflex system to exclude the possible deleterious
      effect on orthostatic tolerance. METHOD: In anesthetized 8 and 6 rabbits, we
      examined static and dynamic characteristics of baroreflex, respectively, with and
      without electrical acupuncture (1 Hz, 5 mA, and 5msec). Dynamic characteristics
      were examined by imposing pseudorandom binary changes in isolated carotid sinus
      pressure. RESULTS: With the stimulation condition to decrease arterial blood
      pressure and sympathetic nerve activity (resulted form decreased response range
      of neural arc), either of the dynamic characteristics of neural arc or those of
      peripheral arc did not change by electrical acupuncture at Zusanli. CONCLUSION:
      We conclude that application of electrical acupuncture at Zusanli can suppress
      sympathetic nerve activity but does not affect the dynamic characteristics of the
      arterial baroreflex system, indicating no deleterious effect on orthostatic
      tolerance.

PMID- 19163081
TI  - Noninvasive transcutaneous bionic baroreflex system prevents severe orthostatic
      hypotension in patients with spinal cord injury.
AB  - Central baroreflex failure in patients with spinal cord injury results in serious
      orthostatic hypotension. We examined if transcutaneous electrical stimulation
      regulates arterial pressure in those patients. We identified skin regions capable
      of increasing arterial pressure and determined respective transfer function.
      Using the transfer function, we designed the feedback regulator (i.e., bionic
      baroreflex system) to control arterial pressure. Orthostatic stress decreased
      arterial pressure profoundly. Activation of bionic regulator restored and
      maintained arterial pressure at pre-specified levels. We conclude that the
      transcutaneous bionic system is noninvasive and capable of stabilizing arterial
      pressure in patients with spinal cord injury.

PMID- 19163082
TI  - Increased complexity of short-term heart rate variability in hyperthyroid
      patients during orthostatic challenge.
AB  - Hyperthyroidism is a pathological condition characterized by an altered autonomic
      cardiovascular control, resulting in an increase of the sympathetic and a
      decrease of the parasympathetic modulation of heart rate variability. Recently,
      the entropy-based indices derived from short-term heart period variability have
      been proved to be helpful in evaluating the autonomic cardiovascular modulation.
      The aim of our study was to evaluate the autonomic cardiovascular modulation of
      hyperthyroid subjects at rest and during standing using spectral parameters and
      corrected conditional entropy indices derived from short-term heart period
      variability in 12 hyperthyroid (HYPTH) and 9 normal healthy (N) females. Mean
      heart period was significantly decreased by standing both in N and HYPTH and the
      LF power expressed in normalized units was increased. The respiratory rate was
      faster in the HYPTH group compared to N and complexity was significantly greater
      in HYPTH compared to N during standing. Results suggested an enhanced complexity
      of cardiovascular control in HYPTH, more evident in a condition of sympathetic
      activation. The increased complexity of the cardiovascular regulation is probably
      not completely due to autonomic control but also to other influences, such as
      metabolic effects of thyroid hormones impinging upon respiratory control
      mechanisms and, therefore, on cardiorespiratory coupling.

PMID- 19163083
TI  - Assessment of techniques used to evaluate the effect of posture and cardiac
      output on cerebral autoregulation.
AB  - In this study, the role of cardiac output in Cerebral Autoregulation was
      assessed. Mean arterial pressure, cerebral blood flow velocity (middle and
      anterior cerebral artery), stroke volume, cardiac output, total peripheral
      resistance and cerebral autoregulatory index were assessed in 3 healthy young
      males and 4 healthy young females during seated and upright thigh cuff testing.
      Two different methods (long axis left ventricular echocardiography and Modelflow)
      of evaluating stroke volume and cardiac output were compared. The results showed
      that cerebral autoregulation was less effective in the upright posture in all
      subjects. Females had better autoregulation in the anterior cerebral artery,
      whereas males had better autoregulation in the middle cerebral artery. Cardiac
      output does not appear to play an important role in cerebral autoregulation
      during thigh cuff testing. Estimations of cardiac output and stroke volume did
      not strongly correlate between Modeflow and long axis left ventricular
      echocardiography.

PMID- 19163084
TI  - Abnormal cardiac autonomic control in sickle cell disease following transient
      hypoxia.
AB  - Abnormalities in autonomic control in sickle cell anemia (SCA) patients have been
      reported by multiple researchers. However their potential causal association with
      sickle cell crisis remains unknown. We employed hypoxia, a known trigger to
      sickle cell crisis, to perturb the autonomic systems of the subjects. Cardiac
      autonomic control was non-invasively assessed by tracking the changes in heart
      rate variability (HRV) that occur following brief exposure to a hypoxia stimulus.
      Time varying spectral analysis of HRV was applied to estimate the cardiac
      autonomic response to the transient episode of hypoxia. The results demonstrate
      that cardiovascular autonomic response to hypoxia is substantially more sensitive
      in SCA than in normal controls. We also developed a model to compensate for the
      confounding effects of respiration on the HRV spectral indices by using the
      corresponding respiration signal to compensate for the respiratory correlated
      part of the HRV. This technique improved the resolution with which the effect of
      hypoxia on changes in HRV could be measured.

PMID- 19163085
TI  - Multiscale sample entropy in heart rate variability of aortic stenosis patients.
AB  - In the present document the multiscale entropy (MSE) methodology has been applied
      to analyze the complex behavior of the heart rate variability (HRV), in patients
      with aortic stenosis (AS). A set of healthy voluntaries have been used as a
      control group. MSE analysis calculates an entropy rate over different time scales
      to assess the complexity of time series, evaluating short-term and long-term
      correlations. Daytime and nighttime have been considered to study variations of
      the complexity inside the same group of population. A statistical analysis showed
      that entropy was significantly higher in healthy subjects than in AS subjects in
      all the scales during daytime, with exception at scale 1. During nighttime,
      entropy in healthy subjects was significantly higher than in AS subjects only in
      scales from 1 to 7. Multiscale entropy is helpful to characterize AS patients and
      distinguish them from healthy subjects.

PMID- 19163086
TI  - Neural cache: a low-power online digital spike-sorting architecture.
AB  - Transmitting large amounts of data sensed by multi-electrode array devices is
      widely considered to be a challenging problem in designing implantable neural
      recording systems. Spike sorting is an important step to reducing the data
      bandwidth before wireless data transmission. The feasibility of spike sorting
      algorithms in scaled CMOS technologies, which typically operate on low frequency
      neural spikes, is determined largely by its power consumption, a dominant portion
      of which is leakage power. Our goal is to explore energy saving architectures for
      online spike sorting without sacrificing performance. In the face of non
      stationary neural data, training is not always a feasible option. We present a
      low-power architecture for real-time online spike sorting that does not require
      any training period and has the capability to quickly respond to the changing
      spike shapes.

PMID- 19163087
TI  - Inferring the stability of LIFE through Brain Machine Interfaces.
AB  - We examine neural signals from Longitudinally implanted Intra-Fascicular
      Electrodes (LIFE) in a chronic, rabbit model. Translation-invariant wavelet de
      noising methods are used to improve S%R. Then traditional template-based spike
      sorting is applied to discriminate single units. We investigate the effect of
      discriminating between identified units on Brain Machine Interface (BMI) decoding
      performance. We infer the stability of LIFE based on decoding performance with
      and without current BMI methods to counter-act electrode neural signal
      degradation.

PMID- 19163088
TI  - Electric impedance sensing during the inhibition of cell-cell adhesion.
AB  - Electric cell impedance sensing (ECIS) was used to monitor the change of in vitro
      neuron-neuron adhesion in response to the blocking of N-Cam, N-Cadherin and L1.
      ECIS is a method in which cell morphology and cell mobility can be indirectly
      measured by changes in intercellular resistance. Antibodies and soluble
      extracellular domains of the cell adhesion molecules N-Cam, N-Cadherin and L1
      were used as blockers of these adhesion molecules on the cell surface. In a 96
      hour aggregation assay on a low adhesive substrate, the effect of mentioned
      blockers on the aggregation was investigated. The N-Cadherin antibody showed
      effective in aggregation inhibition at concentrations of 3 and 10 micrograms/ml.
      Up to 96 hours no aggregation occurred. A similar effect was achieved by the N
      Cadherin protein, although less distinct. Blocking of N-CAM and L1 revealed no
      inhibition of aggregation. Results from impedance measurements correspond to
      those of the aggregation assays. The neuron-neuron adhesion in monolayers was
      inhibited by blocking of cell adhesion molecules and monitored by ECIS.
      Impedances of neuron covered electrodes were significantly lower in the presence
      of N-Cadherin antibody and protein at concentrations of 1, 3 and 10
      micrograms/ml, indicating a less profound binding between adjacent neuron.The
      results from both the aggregation assays and the impedance measurements
      demonstrate the applicability of CAM blocking for the regulation of culture
      topography.

PMID- 19163089
TI  - Hybrid microprobes for chronic implantation in the cerebral cortex.
AB  - This paper reports on a neural device for chronic implantation into the cerebral
      cortex. Silicon microprobes with 36 electrodes arranged on four shafts are
      fabricated using MEMS technology. The hybrid integration of a ribbon cable with
      high flexibility provides the connection of the electrodes to external
      instrumentation. Crosstalk between the channels is investigated, as well as the
      electrode stability for a time period of one month in vitro. Due to the geometry
      and the mechanical stability of these microprobes, insertions are possible
      without the need for prior opening of the dura mater. A dedicated insertion tool
      has been fabricated to achieve a precise insertion of the microprobes and their
      subsequent mechanical decoupling. Additionally, a protection chamber allowing the
      secure attachment of two connector units on the skull is introduced. The short
      time chronic implantation of microprobes showed that neural activity can be
      recorded, including single unit activity, which was present after four days.

PMID- 19163090
TI  - A multi-channel instrumentation system for biosignal recording.
AB  - This paper reports a highly integrated battery operated multi-channel
      instrumentation system intended for physiological signal recording. The mixed
      signal IC has been fabricated in standard 0.5microm 5V 3M-2P CMOS process and
      features 32 instrumentation amplifiers, four 8b SAR ADCs, a wireless power
      interface with Li-ion battery charger, low power bidirectional telemetry and FSM
      controller with power gating control for improved energy efficiency. The chip
      measures 3.2mm by 4.8mm and dissipates approximately 2.1mW when fully
      operational.

PMID- 19163091
TI  - A low-noise receiver for multichannel wireless neural recording.
AB  - We present a high performance wideband receiver for multichannel wireless
      implantable neural recording systems (WINeR) utilizing pulse width modulation of
      time division multiplexed (PWM-TDM) samples. The receiver consists of a 50 MHz
      approximately 1 GHz tunable down-converter with 75 MHz bandwidth, frequency shift
      keying and PWM demodulators, and a high throughput USB interface. Several IF gain
      stages, passive LC filters, and an FPGA-based time-to-digital converter (TDC)
      with time interval resolution of 428 ps have significantly enhanced the receiver
      performance and extended its receiving range. A 2 MB SDRAM is used as a buffer
      between the TDC and USB to ensure continuous throughput for the digitized raw
      data at data rates up to 10 Mb/s. The receiver performance is evaluated with a 6
      channel WINeR transmitter, showing that the entire system input referred noise
      with this receiver is 9.8 and 12.7 microV(rms) at 0.5 and 3.5 m distances,
      respectively, which are equivalent to 8.2 and 7.9 bits of resolution at 640
      ksample/s.

PMID- 19163092
TI  - Identifying rodent olfactory bulb structures with micro-DTI.
AB  - Olfactory bulb (OB) is one of the most developed systems in rodent models with
      complex neuronal organization and anatomical structures. MR diffusion tensor
      imaging (DTI) is a non-invasive technique to probe tissue microstructures by
      examining the diffusion characteristics of water molecules. This paper presents
      how different OB layers can be identified and quantitatively characterized by
      micro-DTI using a specially constructed micro-imaging radio frequency (RF) coil.
      High spatial resolution and high signal to noise ratio (SNR) DTI images of ex
      vivo rat OBs were obtained. Distinct contrasts were observed between various
      olfactory bulb layers in trace map, fractional anisotropy (FA) map and FA color
      map, all in consistency with the known OB neuroanatomy. These experimental
      results demonstrate the utility of micro-DTI in investigation of complex OB
      organization.

PMID- 19163093
TI  - Transmission line effects on the coil noise correlation matrix in MRI.
AB  - Noise correlation is an important topic in radiofrequency (RF) coil design for
      magnetic resonance imaging (MRI). The original noise correlation formula derived
      by Redpath showed correlation depends on the real part of the inverse impedance
      matrix. In this work, we introduce a more generalized formula to include effects
      from transmission lines and preamplifier input impedance mismatch. This formula
      is used to calculate correlation between two-channel circuits connected to
      preamplifiers using transmission lines of variable electrical length. The
      calculated correlation matches well with that measured on the MR scanner and
      suggests transmission line length can be utilized as an additional degree of
      freedom for coil decoupling, and can be adjusted to achieve zero noise
      correlation.

PMID- 19163094
TI  - An insertable P-31 RF coil for dual-frequency magnetic resonance imaging &
      spectroscopy.
AB  - Application of nuclear magnetic resonance spectroscopy in metabolic studies
      usually includes simultaneous excitation at two different frequencies. RF
      coupling between the two coils has been a problem in the past, resulting in
      reduced field strength from the (1)H coil. A modular surface coil was designed
      and constructed for (1)H and (31)P at 4.7 Tesla; RF traps were designed and
      optimized to minimize the field-degrading coupling current, and trap performance
      was analyzed in terms of improvement in signal-to-noise-ratio and field
      sensitivity pattern of the proton coil. The modular design in conjunction with
      the optimized traps permits the possibility of insertion of the phosphorus coil
      as an 'add on' into any other hydrogen coil.

PMID- 19163095
TI  - A ultra high field multi-element transceive volume array for small animal MRI.
AB  - In this work, a dedicated, 9.4T shielded 8-element transceive volume-array for
      large rat MRI applications is designed and the prototype constructed. Angularly
      oriented radiating structured coil elements are used. It is shown that by
      orienting the radiating conductors of the coil element angularly, the RF
      penetration depth can be increased and the mutual coupling effect can be
      regulated to minimum. In addition, experimental results show that the prototype
      can produce homogenous B(1) field and is well suited for the Transmit SENSE
      application and the GRAPPA parallel imaging technique.

PMID- 19163096
TI  - A simple approach to overcoming mutual coupling effects in some transmit array
      coils for magnetic resonance imaging.
AB  - Single Echo Acquisition (SEA) is a method of completely parallel MR imaging that
      uses coil elements for spatial localization during receive, replacing the need
      for phase encoding repetitions. In this receive-only form, SEA imaging requires
      the use of a phase compensation gradient, the value of which is dependent on coil
      geometry, imaging distance from the elements, and element orientation. Operation
      of the arrays in transmit-receive mode, while adding significant complexity, is
      one potential method of eliminating the restrictions imposed by the phase
      compensation gradient. This abstract examines a straightforward current-splitting
      technique to enable parallel transmission for studying the complicated field
      interactions of these array coils in transmit mode.

PMID- 19163097
TI  - Towards a microcoil for intracranial and intraductal MR microscopy.
AB  - Implantable RF-coils have enabled sub-mm resolution magnetic resonance images
      (MRI) of deep structures. Scaling down the size of RF coils has similarly
      provided a gain in signal-to-noise ratio in nuclear-magnetic-resonance
      spectroscopy. By combining both approaches we designed, fabricated, and imaged
      with an implantable microcoil catheter. While typical implantable catheters use a
      transverse magnetization, the axial magnetization of the microcoil provides
      improved sensitivity and allows visualization of the tissue beyond the distal end
      of the catheter. The microcoil catheter was designed with a diameter of 1 mm for
      future integration with intracranial devices, and for intraductal use in breast
      oncology. We modified the NMR-microcoil design to allow implantation of the RF
      coil, by winding the microcoil on medical-grade silicone tubing and incorporating
      leads on the catheter to connect circuit components. In order to achieve proper
      turn spacing, we coated copper wire with 25 microm of biocompatible polymer
      (Parylene C). Tuning and matching circuitry insured that the impedance of the RF
      coil was approximately 50 ohm at the operating frequency for 3-T proton MR
      applications. A duplexer was used to enable use of the microcoil catheter as a
      transceiver. Experimental verification of the coil design was achieved through ex
      vivo imaging of neural tissue. As expected, the microcoil catheter provided
      microscale images with 20-microm in-plane-resolution and 170-microm-thick slices.
      While 3-T MRI typically provides 1 to 30 voxels per-cubic-millimeter, in this
      paper we report that the MRI microcoil can provide hundreds, and even thousands
      of voxels in the same volume.

PMID- 19163098
TI  - Intravascular irreversible electroporation: theoretical and experimental
      feasibility study.
AB  - Irreversible electroporation (IRE) employs microsecond scale, mega-volt/m
      electric field pulses to impair the cell membrane. IRE is emerging as a valuable
      new minimally invasive technique. Of central importance in using IRE is the
      existence of electric fields, which while impairing the cell membrane, do not
      cause thermal Joule heating induced damage to the tissue. Our recent studies
      suggest that IRE could become an important technique to ablate vascular smooth
      muscle cells of the arterial wall and attenuate restenosis following angioplasty.
      This study was done to support the use of IRE in treatment of restenosis and is a
      fundamental investigation on the electric field parameters that can produce non
      thermal IRE ablation of cells on the arterial wall. The study combines time
      dependant finite-element models of the electric field equation and of the bio
      heat equation with Henriques and Moritz thermal damage integral to evaluate the
      range of non-thermal IRE fields for use in blood vessels. The theoretical
      analysis is supported by temperature measurements during intravascular IRE of
      rodent carotid arteries, showing no significant temperature rise.

PMID- 19163099
TI  - An improved magnetic localization and orientation algorithm for wireless capsule
      endoscope.
AB  - In this paper, we propose a novel localization algorithm for tracking a magnet
      inside the capsule endoscope by 3-axis magnetic sensors array. In the algorithm,
      we first use an improved linear algorithm to obtain the localization parameters
      by finding the eigenvector corresponding to the minimum eigenvalue of the
      objective matrix. These parameters are used as the initial guess of the
      localization parameters in the nonlinear localization algorithm, and the
      nonlinear algorithm searches for more appropriate parameters that can minimize
      the objective error function. As the results, we obtain more robust and accurate
      localization results than those by using linear algorithm only. Nevertheless, the
      time efficiency of the nonlinear algorithm is enhanced. The real experimental
      data show that the average localization accuracy is about 2mm and the average
      orientation accuracy is about 1.6 degrees when the magnet moves within the
      sensing area of 240 mm x 240 mm square.

PMID- 19163100
TI  - Laser-pumped endoscopic illumination source.
AB  - Light sources currently employed in endoscopy have a number of disadvantages
      including inefficiency, high temperature, non-uniform illumination, and the
      production of shadow-less images. In this paper, we present a novel endoscopic
      illumination source, based on the use of a blue-violet laser diode in combination
      with a yellow phosphor for the production of white light. By using this approach,
      the resulting illumination source is more compact and potentially more ergonomic
      than those currently used in endoscopy. Spectral measurements of the emitted
      light indicate that it has a colour similar to that of daylight, and images
      obtained under illumination with this light source indicate that it provides more
      uniform illumination and sharper shadows than standard endoscopic light sources.

PMID- 19163101
TI  - Conducting polymer based active catheter for minimally invasive interventions
      inside arteries.
AB  - An active catheter intended for controllable intravascular maneuvers is presented
      and initial experimental results are shown. A commercial catheter is coated with
      polypyrrole and laser micromachined into electrodes, which are electrochemically
      activated, leading to bending of the catheter. The catheter's electro-chemo
      mechanical properties are theoretically modeled to design the first prototype
      device, and used to predict an optimal polypyrrole thickness for the desired
      degree of bending within approximately 30 seconds. We compared the experimental
      result of catheter bending to the theoretical model with estimated
      electrochemical strain, showing reasonable agreement. Finally, we used the model
      to design an encapsulated catheter with polypyrrole actuation for improved
      intravascular compatibility and performance.

PMID- 19163102
TI  - Microbubble-mediated oxygen delivery to hypoxic tissues as a new therapeutic
      device.
AB  - Chitosan-coated oxygen microbubbles of average diameter 2.5 mum, narrow size
      distribution and spherical shape were prepared. A core-shell structure was
      evidenced by fluorescence microscopy using fluorescent microbubbles. Such
      microbubbles can be a therapeutic device for vehiculating oxygen to hypoxic
      tissues, provided they show proper permeability and diffusivity properties and
      are non-toxic. Our study proves that oxygen is efficiently delivered both in 'in
      vitro' and 'in vivo' preparations, and can be conveniently metabolized reversing
      the cellular hypoxic response. Moreover, toxic effects were investigated in human
      blood and in cultured cells and no evidence for them was found.

PMID- 19163103
TI  - Monitoring activity patterns and trends of older adults.
AB  - This paper presents a pattern mining model developed for the continuous
      monitoring of high level activities and home-based behaviors for functional and
      cognitive status assessment with ambient assisted living systems such as in the
      EU-funded SOPRANO project. Motivating older people to engage in regular physical
      exercise is a key task of SOPRANO to improve health status and executive
      functions. A case study has been elaborated through software simulations to show
      how physical everyday life activity such as walking or sitting could be assessed
      and controlled for a better health lifestyle using the model.

PMID- 19163104
TI  - Identification of inactivity behavior in smart home.
AB  - To help elderly people live independently at home, the TIMC-IMAG laboratory
      developed Health Smart Homes called 'HIS'. These smart Homes are composed of
      several sensors to monitor the activities of daily living of the patients.
      Volunteers have accepted to be monitored during 2 years in their own flats.
      During one year, we carried out our survey on one elderly patient. Thanks to this
      experimentation, we will access to relevant information like physiological,
      environmental and activity. This paper focuses on daily living activity. We will
      introduce an original data splitting method based on the relationship between the
      frame of time and the location in the flat. Moreover we will present two
      different methods to determine a threshold of critical inactivity and eventually
      we will discuss their possible utilities.

PMID- 19163105
TI  - A preliminary study of using wireless kinematic sensors to identify basic
      Activities of Daily Living.
AB  - The objective of this on-going work is to evaluate the accuracy and reliability
      of wireless kinematic sensors in identifying basic Activities of Daily Living
      (ADL). A preliminary trial was conducted consisting of 5 subjects; 3 male (mean:
      23.6, SD: 2.41). Four kinematic sensors were placed on a subject; (a) mid
      sternum, (b) underneath the left armpit, (c) above the right hip and (d) the
      ankle of the dominant leg. A fifth sensor, the activPAL Trio was attached to a
      subject on the thigh of the non-dominant leg. Each subject initially performed a
      range of basic activities in a controlled laboratory setting. Subjects were then
      asked to carry out similar self-annotated activities in a random order and in an
      unsupervised environment.Using 10-fold cross validation the decision tree
      algorithm C4.5 was employed to detect the ADL's. Several configurations of sensor
      placement were compared. The combination of sensors placed on the ankle and hip
      had the highest recognition rate of 81.2%. Single sensor placement was also
      compared with the ankle of the dominant leg having the highest recognition rate
      of 77.4%.

PMID- 19163106
TI  - Learning under uncertainty in smart home environments.
AB  - Technologies and services for the home environment can provide levels of
      independence for elderly people to support 'ageing in place'. Learning
      inhabitants' patterns of carrying out daily activities is a crucial component of
      these technological solutions with sensor technologies being at the core of such
      smart environments. Nevertheless, identifying high-level activities from low
      level sensor events can be a challenge, as information may be unreliable
      resulting in incomplete data. Our work addresses the issues of learning in the
      presence of incomplete data along with the identification and the prediction of
      inhabitants and their activities under such uncertainty. We show via the
      evaluation results that our approach also offers the ability to assess the impact
      of various sensors in the activity recognition process. The benefit of this work
      is that future predictions can be utilised in a proposed intervention mechanism
      in a real smart home environment.

PMID- 19163107
TI  - Robust Common Spatial Patterns for EEG signal preprocessing.
AB  - The Common Spatial Patterns (CSP) algorithm finds spatial filters that are useful
      in discriminating different classes of electroencephalogram (EEG) signals such as
      those corresponding to different types of motor activities. This algorithm is
      however, sensitive to outliers because it involves the estimation of covariance
      matrices. Classical sample covariance estimates are easily affected even if a
      single outlier exists. To improve the CSP algorithm's robustness against
      outliers, this paper first investigates how multivariate outliers affect the
      performance of the CSP algorithm. We then propose a modified version of the
      algorithm whereby the classical covariance estimates are replaced by the robust
      covariance estimates obtained using Minimum Covariance Determinant (MCD)
      estimator. Median Absolute Deviation (MAD) is also used to robustly estimate the
      variance of the projected EEG signals. The results show that the proposed
      algorithm is able to reduce the influence of the outliers. When an average of
      2.5% outliers is introduced, the average drop in the accuracy is 9.21% for the
      CSP algorithm and 0.72% for the proposed algorithm.

PMID- 19163108
TI  - Spatio-temporal modeling for dense array ERP classification.
AB  - A new strategy is introduced to exploit the enhanced spatial resolution offered
      by dense electrode arrays and to solve the dimensionality problem that plagues
      the design and evaluation of practical dense array event-related potential (ERP)
      classifiers. A spatio-temporal model is introduced to observe the dense array ERP
      amplitude variations across channels and time, simultaneously. Dimensionality
      reduction is achieved by selecting elements of the spatio-temporal arrays which
      differ in their probability distributions across the brain activity classes. Each
      selected spatio-temporal element is classified using an univariate Gaussian
      classifier and the resulting decisions are fused into a decision fusion vector
      which is classified using a discrete Bayes vector classifier. Using ERPs from a
      Stroop color test, it is shown that the performance improves significantly when
      the strategy is applied to normalized spatio-temporal ERP arrays. The main
      advantage of the new strategy is that it is not constrained by the dimensionality
      of the ERP vector. Consequently, it can be used to design ERP classifiers
      specialized for individual test subjects without having to collect a large number
      of ERPs from groups of subjects in order to solve the dimensionality problem.

PMID- 19163109
TI  - Self-paced BCI using multiple SWT-based classifiers.
AB  - The presence of false activations inhibits the use of existing self-paced BCIs in
      real life applications. We present a new design method for a self-paced BCI that
      yielded 0% false activations using the data of two subjects. This system obtains
      templates/shapes of the movement related finger flexion patterns. To obtain the
      templates, the intentional control data are decomposed into 5 levels using the
      stationary wavelet transform. Then, ensemble averaging is done. These templates
      are used to train 5 radial basis function neural networks. This is followed by a
      majority voting classifier.

PMID- 19163110
TI  - Modeling and classification of knee-joint vibroarthrographic signals using
      probability density functions estimated with Parzen windows.
AB  - Diagnostic information related to the articular cartilage surfaces of knee-joints
      may be derived from vibro-arthrographic (VAG) signals. Although several studies
      have proposed many different types of parameters for the analysis and
      classification of VAG signals, no statistical modeling methods have been explored
      to represent the fundamental distinctions between normal and abnormal VAG
      signals. In the present work, we derive models of probability density functions
      (PDFs), using the Parzen-window approach, to represent the basic statistical
      characteristics of normal and abnormal VAG signals. The Kullback-Leibler distance
      (KLD) is then computed between the PDF of the signal to be classified and the PDF
      models for normal and abnormal VAG signals. A classification accuracy of 73.03%
      was obtained with a database of 89 VAG signals. The screening efficiency was
      derived to be 0.6724, in terms of the area under the receiver operating
      characteristics curve.

PMID- 19163111
TI  - Hand motion discrimination by EMG signals without incorrect discriminations that
      elbow motions cause.
AB  - The objective of this research is to develop a hand motion discrimination method
      that uses electromyogram (EMG) signals for controlling myoelectric prosthetic
      hands without the incorrect discriminations that elbow motions cause. We proposed
      a method that can discriminate hand motions using linear multiple regression
      models in the past. However, this method incorrectly discriminates hand motions
      when elbow motions are performed. The incorrect discriminations hamper
      myoelectric prosthetic hand use. To solve this problem, we propose a hand
      discrimination method using conic models. In the experiment, we prove that the
      proposed method can discriminate hand motions without the incorrect
      discriminations.

PMID- 19163112
TI  - Antiepileptic drug intervention decouples electroencephalogram (EEG) signals: a
      case study in Unverricht-Lundborg Disease.
AB  - Change in severity of myoclonus as an outcome measure of antiepileptic drug (AED)
      treatment in patients with Unverricht-Lundborg Disease (ULD) has been estimated
      by utilizing the Unified Myoclonus Rating Scale (UMRS). In this study, we measure
      treatment effects through EEG analysis using mutual information approach to
      quantify interdependence/coupling strength among different electrode sites.
      Mutual information is known to have the ability to capture linear and non-linear
      dependencies between EEG time series with superior performance over the
      traditional linear measures. One subject with ULD participated in this study and
      1-hour EEG recordings were acquired before and after treatment of AED. Our
      results indicate that the mutual information is significantly lower after taking
      the add-on AED for four weeks at least. This finding could lead to a new insight
      for developing a new outcome measure for patient with ULD, when UMRS could
      potentially fail to detect a significant difference.

PMID- 19163113
TI  - Renyi entropy and Lempel-Ziv complexity of mechanomyographic recordings of
      diaphragm muscle as indexes of respiratory effort.
AB  - The study of the mechanomyographic (MMG) signals of respiratory muscles is a
      promising technique in order to evaluate the respiratory muscles effort. A new
      approach for quantifying the relationship between respiratory MMG signals and
      respiratory effort is presented by analyzing the spatio-temporal patterns in the
      MMG signal using two non-linear methods: Renyi entropy and Lempel-Ziv (LZ)
      complexity analysis. Both methods are well suited to the analysis of non
      stationary biomedical signals of short length. In this study, MMG signals of the
      diaphragm muscle acquired by means of a capacitive accelerometer applied on the
      costal wall were analyzed. The method was tested on an animal model (dogs), and
      the diaphragmatic MMG signal was recorded continuously while two non anesthetized
      mongrel dogs performed a spontaneous ventilation protocol with an incremental
      inspiratory load. The performance in discriminating high and low respiratory
      effort levels with these two methods was analyzed with the evaluation of the
      Pearson correlation coefficient between the MMG parameters and respiratory effort
      parameters extracted from the inspiratory pressure signal. The results obtained
      show an increase of the MMG signal Renyi entropy and LZ complexity values with
      the increase of the respiratory effort. Compared with other parameters analyzed
      in previous works, both Renyi entropy and LZ complexity indexes demonstrates
      better performance in all the signals analyzed. Our results suggest that these
      non-linear techniques are useful to detect and quantify changes in the
      respiratory effort by analyzing MMG respiratory signals.

PMID- 19163114
TI  - Circadian variations of short-term heart period irreversibility in healthy and
      chronic heart failure patients.
AB  - We exploited time irreversibility analysis to characterize short heart period
      sequences (256 samples) derived from 24h Holter recordings in normal healthy (NO)
      subjects and chronic heart failure (CHF) patients. We found a significant
      presence of irreversible dynamics over short time scales, whereas over dominant,
      longer time scales irreversibility was marginal. Over short time scales in NO
      subjects the percentage of irreversible dynamics was larger during daytime than
      during nighttime, thus indicating a larger presence of non linear dynamics during
      daytime. Same circadian variation was detected in CHF patients but the percentage
      of irreversible series was higher. In NO subjects during daytime the non linear
      behavior was mostly the result of bradycardic runs shorter than tachycardic ones.
      In CHF population this pattern was as present as the reverse pattern (i.e.
      tachycardic runs shorter than bradycardic ones). Time irreversibility analysis
      provides useful and reliable indexes even in uncontrolled experimental conditions
      and during daily activities.

PMID- 19163115
TI  - Investigating parameters participating in the infant respiratory control system
      attractor.
AB  - Theoretically, any participating parameter in a non-linear system represents the
      dynamics of the whole system. Taken's time delay embedding theory provides the
      fundamental basis for allowing non-linear analysis to be performed on
      physiological, time-series data. In practice, only one measurable parameter is
      required to be measured to convey an accurate representation of the system
      dynamics. In this paper, the infant respiratory control system is represented
      using three variables-a digitally sampled respiratory inductive plethysmography
      waveform, and the derived parameters tidal volume and inter-breath interval time
      series data. For 14 healthy infants, these data streams were analysed using
      recurrence plot analysis across one night of sleep. The measured attractor size
      of these variables followed the same qualitative trends across the nights study.
      Results suggest that the attractor size measures of the derived IBI and tidal
      volume are representative surrogates for the raw respiratory waveform. The extent
      to which the relative attractor sizes of IBI and tidal volume remain constant
      through changing sleep state could potentially be used to quantify pathology, or
      maturation of breathing control.

PMID- 19163116
TI  - Effects of magnetic fields on intracellular calcium oscillations.
AB  - Based on the model of the two calcium stores developed by Goldbeter, and the
      viewpoint that the cell membrane is a major site of interaction for extremely-low
      frequency (ELF) electromagnetic fields, the permeability of ions can be changed
      by electromagnetic fields, a theoretical model of cytosolic calcium oscillations
      influenced by magnetic fields is presented. It is shown that, the field frequency
      condition will influence the pattern of calcium oscillation while the field
      strength was given, and the magnetic field strength will change the pattern of
      calcium oscillation when the frequency was 50Hz and 100Hz. Therefore,
      intracellular calcium oscillations can be influenced by ELF magnetic fields and
      then a series cellular response could be transformed.

PMID- 19163117
TI  - Heart murmur recognition and segmentation by complexity signatures.
AB  - Heart sound analysis has been a topic of investigation for several years. Since
      heart sounds directly encode the mechanical activity of the heart, they enable
      the assessment and follow-up of several types of heart disorders in pre
      symptomatic states. Murmurs are the most common abnormality signature in many
      heart disorders. This paper introduces an algorithm for heart murmur
      identification. In the presence of murmurs, heart sounds exhibit chaotic
      behavior. In the proposed method this is assessed based upon the nonlinear
      dynamics of the signal. In order to segment murmurs from other heart sound
      components, the signal is transformed into a phase space that is later
      reconstructed using the embedded matrix. Based on the phase space, the complexity
      and the strength of the signal are computed. These features are the basis for
      sound component boundary location. The method has been tested with a database of
      heart sounds that include diverse heart lesions and heart murmurs. The algorithms
      achieved 91.09% sensitivity and 95.25% specificity.

PMID- 19163118
TI  - Predict the neurological recovery under hypothermia after cardiac arrest using C0
      complexity measure of EEG signals.
AB  - Clinical trials have proven the efficacy of therapeutic hypothermia in improving
      the functional outcome after cardiac arrest (CA) compared with the normothermic
      controls. Experimental researches also demonstrated quantitative
      electroencephalogram (qEEG) analysis was associated with the long-term outcome of
      the therapeutic hypothermia in brain injury. Nevertheless, qEEG has not been able
      to provide a prediction earlier than 6h after the return of spontaneous
      circulation (ROSC). In this study, we use C0 complexity to analyze the nonlinear
      characteristic of EEG, which could predict the neurological recovery under
      therapeutic hypothermia during the early phase after asphyxial cardiac arrest in
      rats. Twelve Wistar rats were randomly assigned to 9-min asphyxia injury under
      hypothermia (33 degrees C, n=6) or normothermia (37 degrees C, n=6).
      Significantly greater C0 complexity was found in hypothermic group than that in
      normothermic group as early as 4h after the ROSC (P0.05). C0 complexity at 4h
      correlated well with the 72h neurodeficit score (NDS) (Pearson's correlation =
      0.882). The results showed that the C0 complexity could be an early predictor of
      the long-term neurological recovery from cardiac arrest.

PMID- 19163119
TI  - On the application of the auto mutual information rate of decrease to biomedical
      signals.
AB  - The auto mutual information function (AMIF) evaluates the signal predictability
      by assessing linear and non-linear dependencies between two measurements taken
      from a single time series. Furthermore, the AMIF rate of decrease (AMIFRD) is
      correlated with signal entropy. This metric has been used to analyze biomedical
      data, including cardiac and brain activity recordings. Hence, the AMIFRD can be a
      relevant parameter in the context of biomedical signal analysis. Thus, in this
      pilot study, we have analyzed a synthetic sequence (a Lorenz system) and real
      biosignals (electroencephalograms recorded with eyes open and closed) with the
      AMIFRD. We aimed at illustrating the application of this parameter to biomedical
      time series. Our results show that the AMIFRD can detect changes in the non
      linear dynamics of a sequence and that it can distinguish different physiological
      conditions.

PMID- 19163120
TI  - Fetal heart rate detection in multivariate abdominal ECG recordings using non
      linear analysis.
AB  - A novel three-stage methodology for the detection of fetal heart rate (fHR) from
      multivariate abdominal electrocardiogram (ECG) recordings is introduced. In the
      first stage, the maternal R-peaks and fiducial points (maternal QRS onset and
      offset) are detected. Maternal fiducial points are used to eliminate the maternal
      QRS complexes from the abdominal ECG recordings. In the second stage, two
      denoising procedures are applied to enhance the fetal QRS complexes. The phase
      space characteristics are employed to identify fetal heart beats not overlapping
      with the maternal QRSs which are eliminated in the first stage. The extraction of
      the fetal heart rate is accomplished in the third stage, using a histogram based
      technique in order to identify the location of the fetal heart beats which
      overlap with the maternal QRSs. The methodology is evaluated on simulated and
      real multichannel ECG signals. In both cases, the obtained results indicate high
      performance; in the simulated ECGs the accuracy ranges from 74.21-100%, depending
      on the employed SNR, while in the real recordings the average accuracy is 94.08%.

PMID- 19163122
TI  - Effect of LCDs displaying blurred images on the postural control system.
AB  - In order to evaluate display devices, a geostationary image and the character
      were generally used in previous studies. We have proposed a new method for
      comparing the standing posture when a subject views a liquid crystal display
      (LCD) displaying a movie scrolling from the left to the right. In this study, we
      mathematically measured the degree of determinism in the dynamics of the sway of
      center-of-gravity. The Double-Wayland algorithm was used as a novel method. As a
      result, the dynamics of the sway when subjects viewed the movie as well that of
      the sway in the resting state was considered to be stochastic. The moving map
      task would not change it into a deterministic one.

PMID- 19163121
TI  - Comparison of nonlinear indices in analyses of heart rate variability.
AB  - Recent advances in study of heart rate variability (HRV) call for a paradigm
      shift from linear to nonlinear analysis. However, whether HRV per se is chaotic
      or merely random has remained an open problem. Myriad idealized measures of
      nonlinear dynamics or fractals which have been proposed in the literatures to
      characterize HRV are limited by their sensitivity to discernable noise. In this
      work, we compare the robustness of some nonlinear indices and evaluate their
      applicability to HRV analysis in the presence of noise.

PMID- 19163123
TI  - Nonlinear forecasting measurement of magnetoencephalogram recordings from
      Alzheimer's disease patients.
AB  - The goal of this study was to analyze the magnetoencephalogram (MEG) background
      activity in patients with Alzheimer's disease (AD) using a nonlinear forecasting
      measure. It is a nonparametric method to quantify the predictability of time
      series. Five minutes of recording were acquired with a 148-channel whole-head
      magnetometer in 15 patients with probable AD and 15 elderly control subjects.
      Stationary epochs of 5 seconds (848 points, sample frequency of 169.55 Hz) were
      selected. Our results showed that AD patients' MEGs were more predictable than
      controls' recordings. Additionally, an accuracy of 76.7% (80.0% sensitivity;
      73.3% specificity) was reached using a receiver operating characteristic curve.
      These preliminary results suggest the usefulness of nonlinear forecasting to gain
      a better understanding of dynamical processes underlying the MEG recording.

PMID- 19163124
TI  - Non-linear modeling of the steady-state disturbance term in isometric force.
AB  - The analysis of isometric force may provide early detection of certain types of
      neuropathology such as Parkinson's disease. Our long term goal is to determine if
      there are detectable differences between model parameters of healthy and
      unhealthy individuals. In this study we evaluate nonlinear dynamic system models
      of isometric force using Hammerstien models. The experiments involved subjects
      exerting isometric force over a range from 5% to 95% of maximal voluntary
      contraction. The findings suggest that the Hammerstien models provide adequate
      fit, reducing the number of nonlinear difference equations of higher order that
      were determined in our earlier work.

PMID- 19163125
TI  - The influence of urine volume on body impedance measurement.
AB  - Bio-signal has some characteristics that the signal is so weak. So, it is good
      that the factors to influence measured electrical signal are eliminated as much
      as they can. So, in this paper we will show the influence of urine in bladder on
      measuring human body impedance. Human urine has different conductivity from other
      human tissues. Therefore, if the volume of the urine changed, the measured body
      impedance data also changed.So, in this paper, we will show the influence of
      urine in bladder with foot-to-foot and thigh-to-thigh current paths. As a result,
      if the current flows through human bladder, the influence of urine in the bladder
      must be considered when the body impedance is measured

PMID- 19163126
TI  - Bayesian model order selection for nonlinear system function expansions.
AB  - Orthonormal function expansions have been used extensively in the context of
      linear and nonlinear systems identification, since they result in a significant
      reduction in the number of required free parameters. In particular, Laguerre
      basis expansions of Volterra kernels have been used successfully for
      physiological systems identification, due to the exponential decaying
      characteristics of the Laguerre orthonormal basis and the inherent nonlinearities
      that characterize such systems. A critical aspect of the Laguerre expansion
      technique is the selection of the model structural parameters, i.e., polynomial
      model order, number of Laguerre functions in the expansion and value of the
      Laguerre parameter alpha, which determines the rate of exponential decay. This
      selection is typically made by trial-and-error procedures on the basis of the
      model prediction error. In the present paper, we formulate the Laguerre expansion
      technique in a Bayesian framework and derive analytically the posterior
      distribution of the alpha parameter, as well as the model evidence, in order to
      infer on the expansion structural parameters. We also demonstrate the performance
      of the proposed method by simulated examples and compare it to alternative
      statistical criteria for model order selection.

PMID- 19163127
TI  - Progressive trypsin digestion and serum inhibition in articular cartilage
      monitored using high-frequency ultrasound in situ.
AB  - This study investigated the trypsin digestion and serum inhibition in articular
      cartilage monitored using high-frequency ultrasound system in situ. Three normal
      bovine patellae were obtained from a local butcher shop. Four full-thickness
      cartilage-bone specimens were prepared from the lower medial side of each patella
      and divided into 4 groups: Group A, B, C and D. Group A was treated as control.
      The samples from the other three groups were digested by trypsin for 40 minutes
      and then were immersed for 280 additional minutes in trypsin, physiological
      saline, or fetal bovine serum (FBS), respectively. It was measured in the M-mode
      ultrasound images that 30% to 54% of the full-thickness cartilage tissue for all
      the samples was digested by the 40-minute trypsin digestion. The continuous
      trypsin digestion depleted almost all proteoglycan (PG) content of the samples of
      Group B. For Group C, the residual enzyme digestion in saline generated a
      digestion extension only slightly less than that of Group B. The enzyme digestion
      in the samples of Group D was relatively quickly (approximately 1 hour) stopped
      by FBS. The final ultrasound data were compared to histology for assessing the PG
      depletion. Our findings provide important information of enzyme digestion and
      inhibition inside articular cartilage. Ultrasound represents a useful visual tool
      to evaluate the dynamics of models of OA in cartilage specimens in vitro.

PMID- 19163128
TI  - High frequency ultrasound imaging of surface and subsurface structures of
      fingerprints.
AB  - High frequency ultrasound is suitable for non-invasive evaluation of skin because
      it can obtain both morphological and biomechanical information. A specially
      developed acoustic microscope system with the central frequency of 100 MHz was
      developed. The system was capable of (1) conventional C-mode acoustic microscope
      imaging of thinly sliced tissue, (2) ultrasound impedance imaging of the surface
      of in vivo thick tissue and (3) 3D ultrasound imaging of inside of the in vivo
      tissue. In the present study, ultrasound impedance imaging and 3D ultrasound
      imaging of in vivo fingerprints were obtained. The impedance image showed pores
      of the sweat glands in the surface of fingerprint and 3D ultrasound imaging
      showed glands of the rear surface of fingerprint. Both findings were not
      visualized by normal optical imaging, thus the system can be applied to
      pathological diagnosis of skin lesions and assessment of aging of the skin in
      cosmetic point of view.

PMID- 19163129
TI  - Acoustic lens characterization for ultrasound and photoacoustic C-scan imaging
      modalities.
AB  - From a fundamental perspective, image reconstruction tasks in both ultrasound
      pulse echo and photoacoustic imaging are identical. We propose a C-scan imaging
      scheme that is applicable to both modalities where the image reconstruction is
      achieved through focusing action of an acoustic lens. The theory to characterize
      the imaging system is presented. Experimental methodology to determine the system
      point-spread-function is outlined and demonstrated with preliminary results.

PMID- 19163130
TI  - Modified time-of-flight based calibration approach for ultrasonic computed
      tomography.
AB  - In the previous paper [11], a method for geometrical and transducer-time-delay
      auto-calibration of an ultrasonic computed tomography (USCT) system has been
      described, aiming at calibration of individual ultrasonic (US) transducer
      positions. The present contribution describes a novel modification of the method
      utilizing the particular USCT system concept: the exactly known spatial relations
      among transducers grouped in each of the transducer array systems (TASes). The
      algorithms used for the calibration remain based on the principles similar to the
      global positioning system (GPS) navigation, however, the positions and
      orientations of complete TASes are calibrated, rather than individual positions
      of transducers. This way, the number of unknowns is substantially reduced while
      the number of available equations remains unchanged. Consequently, a solution
      substantially more robust with respect to measurement noise can be obtained based
      on this highly overdetermined equation system. The method is capable of
      calibrating the individual positions of all ultrasonic transducers via their
      positions in TASes as well as their individual time delays at once during sc.
      empty measurement, without a need for any particular arrangements, e.g.
      calibration phantoms.

PMID- 19163131
TI  - High frequency ultrasound characterization of artificial skin.
AB  - Regenerated skin with 3-dimensional structure is desired for the treatment of
      large burn and for the plastic surgery. High frequency ultrasound is suitable for
      non-destructive testing of the skin model because it provides information on
      morphology and mechanical properties. In this paper, spectral parameters of
      ultrasound radio-frequency signal from a specially developed high-frequency
      ultrasound imaging system were evaluated for tissue characterization of
      artificial skin. Results suggest that spectral parameters are useful for
      classification of epidermis and dermis in the artificial skin model. The system
      is also a useful tool for the noninvasive and nondestructive evaluation of skin.

PMID- 19163132
TI  - Retinex enhancement of infrared images.
AB  - With the ability of imaging the temperature distribution of body, infrared
      imaging is promising in diagnostication and prognostication of diseases. However
      the poor quality of the raw original infrared images prevented applications and
      one of the essential problems is the low contrast appearance of the imagined
      object. In this paper, the image enhancement technique based on the Retinex
      theory is studied, which is a process that automatically retrieve the visual
      realism to images. The algorithms, including Frackle-McCann algorithm, McCann99
      algorithm, single-scale Retinex algorithm, multi-scale Retinex algorithm and
      multi-scale Retinex algorithm with color restoration, are experienced to the
      enhancement of infrared images. The entropy measurements along with the visual
      inspection were compared and results shown the algorithms based on Retinex theory
      have the ability in enhancing the infrared image. Out of the algorithms compared,
      MSRCR demonstrated the best performance.

PMID- 19163133
TI  - Towards more adequate colour histograms for in-body images.
AB  - Although there is a growing number of scientific papers describing classification
      of in-body images, most of it is based on traditional colour histograms. In this
      paper we explain why these might not be the most adequate visual features for in
      body image classification. Based on a colour dynamic range maximization
      criterion, we propose a methodology for creating more adequate colour histograms,
      testing it on a vital-stained magnification endoscopy scenario.

PMID- 19163134
TI  - Temporal 2D reconstruction of cell nucleus from Fluorescence Confocal Microscopy
      images with anisotropic filtering.
AB  - Fluorescence Confocal Microscopy(FCM) is nowadays one of the most important tools
      in biomedicine research. In fact, it makes possible to accurately study the
      dynamic processes occurring inside the cell and its nucleus by following the
      motion of fluorescent molecules along the time. Due to the small amount of
      acquired radiation and the huge optical and electronics amplification, the FCM
      images are usually corrupted by a severe type of Poisson noise. This noise may be
      even more damaging when very low intensity incident radiation is used to avoid
      phototoxicity. In this paper, a Bayesian algorithm is proposed to remove the
      Poisson multiplicative noise corrupting the FCM images. The observation are
      organized in a 3D tensor where each plane is one of the images acquired along the
      time of a cell using the Fluorescence Loss In Photobleaching (FLIP) technique.
      The method removes simultaneously the noise by considering different spatial and
      temporal correlations. This is done by using an anisotropic 3D filter that may be
      separately tunned in space and time dimensions. Tests using synthetic and real
      data are described and presented to illustrate the application of the algorithm.

PMID- 19163135
TI  - Contrast enhancement of mammography images using a fuzzy approach.
AB  - In this paper, a fuzzy operator for contrast enhancement of mammography images is
      presented. This intensity modification method is effective and fast in computing.
      In this approach, the selection of appropriate parameters for the required
      transformations is performed based on the specific image characteristics. Images
      are first transformed using a fuzzification function. We then apply an algorithm
      for intensity adaptation based on involutive fuzzy complements and measures of
      fuzziness. Regarding to the amount of ambiguity the proposed technique detects
      the suitable form of the modification in the set of involutive membership
      function. Finally, the defuzzification procedure is performed to transform the
      modified image back to the spatial domain. The experimental results show that
      this method can enhance the region of interest in mammography images that is
      useful for breast cancer diagnosis.

PMID- 19163136
TI  - Fluorescence Confocal Microscopy imaging denoising with photobleaching.
AB  - The Fluorescence Confocal Microscopy (FCM) is nowadays one of the most important
      tools in biomedical and pharmaceutic research. The main advantage of this
      technique over the traditional bright field optical microscopy is the fact that
      it allows the selection of a thin cross-section of the sample by rejecting the
      visual information coming from the out-of-focus planes. However, the small amount
      of energy radiated by the fluorophore and the huge light amplification performed
      by the photon detector to capture this visual information introduces a type of
      multiplicative noise described by a Poisson distribution. Additionally, the
      radiation efficiency of the fluorophore decreases with the time, an effect called
      photobleaching, leading to a decrease in the image intensity along the time. In
      this paper, a reconstruction algorithm is proposed where the multiplicative noise
      and the photobleaching effect are modeled. The goal is to obtain the morphology
      and the intensity decay rate across the cell nucleus from a sequence of FCM
      images. The reconstruction algorithm is formulated as an optimization problem
      where a convex energy function is minimized. Tests using synthetic and real data
      are presented to illustrate the application of the algorithm and the
      effectiveness of the results.

PMID- 19163137
TI  - Dual apodization with cross-correlation in the presence of phase aberration and
      noise.
AB  - We have recently presented a new method to suppress side lobes and clutter in
      ultrasound imaging called dual apodization with cross-correlation or DAX. This
      method uses two apodization functions in receive mode which yield point spread
      functions with very similar main lobes but different side lobes and clutter.
      These similarities and differences are quantified by using normalized cross
      correlation of the radio frequency (RF) data in the axial direction. These cross
      correlation coefficients serve as a pixel-by-pixel weighting or filter to pass
      main lobe dominated signals and suppress clutter dominated signals. In this
      paper, we evaluate the robustness of DAX in the presence of phase aberration and
      noise. Aberrating layers of pig skin, fat, and muscle were used experimentally to
      mimic different level of aberrators. Experimental results are also presented
      using DAX in the presence of noise. With system signal-to-noise ratio (SNR) of at
      least 15 dB, we have a contrast-to-noise ratio (CNR) improvement of over 100 %
      compared to standard beamforming. This work shows that DAX is able to reliably
      improve contrast-to-noise ratio in the presence of phase aberration and noise.

PMID- 19163138
TI  - Proposal of differential volume rendering reconstruction from X-ray fluoroscopy
      for clinical veterinary medicine.
AB  - 3D reconstruction from ordinary X-ray equipment which is not CT or MRI is
      required in clinical veterinary medicine. In this paper, we propose a method for
      3D-reconstruction from X-ray fluoroscopy for clinical veterinary medicine.
      Fluoroscopy is usually used to observe a movement of organ or to identify a
      position of organ for surgery by weak X-ray intensity. A problem arises due to
      weak X-ray intensity. Although fluoroscopy can present information of not only
      bone structure but soft tissues, the contrast is very low and it is very
      difficult to recognize some soft tissues. To solve this problem, this paper
      proposes a new method to determine opacity in volume rendering process. The
      opacity is determined according to 3D differential coefficient of 3D
      reconstruction. This differential volume rendering can present a 3D structure
      image of multiple organs volumetrically and clearly for clinical veterinary
      medicine. This paper shows results of experimental investigation of small dog.

PMID- 19163139
TI  - Fast histogram equalization for medical image enhancement.
AB  - To overcome the problem that the histogram equalization can fail for discrete
      images, a local-mean based strict pixel ordering method has been proposed
      recently, although it is unpractical for 3D medical image enhancement due to its
      complex computation. In this paper, a novel histogram mapping method is proposed.
      It uses a fast local feature generation technique to establish a combined
      histogram that represents voxels' local means as well as grey levels. Different
      sections of the combined histogram, separated by individual peaks, are
      independently mapped into the target histogram scale under the constraint that
      the final overall histogram should be as uniform as possible. By using this
      method, the speed of histogram equalization is dramatically improved, and the
      satisfactory enhancement results are also achieved.

PMID- 19163140
TI  - Correction of inhomogeneities in Magnetic Resonance Images.
AB  - This paper presents a method by which two fast spoiled gradient echo image
      volumes can be used to estimate the slowly varying intensity variation frequently
      observed in Magnetic Resonance Images (MRI). We first present results for
      simulated brain MRI, where we compare the performance of a segmentation algorithm
      on uncorrected, corrected and artifact free images. Next, we present the results
      for a real uniform phantom and then for clinical spinal images, where our
      algorithm reduces the intensity variation within a tissue class from a factor of
      30 to a factor of 2. The technique and algorithm has been successfully tested on
      over 1000 images acquired with different coils, sequences and anatomies.

PMID- 19163141
TI  - Multi-scale model-based vessel enhancement using local line integrals.
AB  - This paper presents a novel vessel enhancement method. By regarding a vessel
      segment as a local line and exploiting the second order information along the
      line, our method embeds a vessel model to capture vessel structures. The vessel
      model is the key to better performances of our method than the Hessian-based
      methods and makes the Hessian-based methods fall in an extreme case of our
      method. It is experimentally shown that our method gives more accurate
      'vesselness' measures and vessel direction estimations. In particular, our method
      achieves better background suppression, smoother 'vesselness' measures inside
      vessels and better responses at crossings (where two relatively straight vessels
      meet).

PMID- 19163142
TI  - Characterization of thyroid nodules by 3-D contrast-enhanced ultrasound imaging.
AB  - High resolution ultrasound imaging proved effective in the detection, analysis,
      and follow-up of thyroid lesions, even if interpretative pitfalls remain.
      Differentiation between malignant and benign nodules is a major challenge:
      malignancy is often correlated to an increase in intranodular vasculature, due to
      rapid angiogenesis. We developed a three-step methodology to reconstruct
      intranodular vasculature based on 3-D contrast-enhanced images: i) preprocessing;
      ii) morphological opening by using a structuring element coherent with the
      microbubbles appearance: iii) thresholding and 3-D representation. We processed
      the volumes relative to 8 nodules (4 benign and 4 malignant, confirmed by needle
      biopsy) and we calculated the percentage of intranodular contrast agent. Results
      confirm that malignant nodules present a higher internal vasculature (52.3% +/-
      15.7%) than benign (14.3% +/- 5.3%). Also, two experts reported the reconstructed
      3-D volumes and scored the nodules characteristics, obtaining a good agreement
      with bioptic results. We believe this methodology could be useful to improve
      nodules differentiation in thyroid ultrasound exams.

PMID- 19163143
TI  - Information measures-based intensity standardization of MRI.
AB  - Scan-to-scan intensity variation, even with the same imaging modality, affects a
      number of intensity-based image processing methods such as feature map based
      segmentation and non-rigid registration techniques that minimize sum of squared
      differences (SSD). Current intensity standardization techniques based on either
      percentile alignment or polynomial mapping suffer from a number of limitations.
      We present a novel intensity standardization techniques that exploits information
      measures obtained from the images. A probability similarity measure obtained by
      using polynomial mapping with Kullback-Leibler (KL) divergence is used for
      intensity standardization of pair-wise magnetic resonance (MR) images. For
      standardization of group-wise MR images, polynomial mapping with minimum entropy
      as a group probability similarity measure is used for attaining standardization
      in a group to attain common feature without bias. Our method is more flexible,
      particularly in mapping high intensity regions, such as lesions, since it does
      not set any hard limit. The mappings were realized through optimization of cost
      functions with Powell's search. The performance of the proposed method is
      demonstrated for non-rigid registration and feature map-based image segmentation
      of MR brain images.

PMID- 19163144
TI  - Physically consistent registration of extraocular muscle models from MRI.
AB  - Building realistic subject-specific models of the orbit from medical images is
      important in biomechanical simulations to improve our understanding of
      extraocular muscle function and the mechanism of human eye movement. With
      advances in MRI techniques, configurations of orbital structures in different
      gazes can be captured. We propose to integrate estimated material properties of
      extraocular muscles in the surface reconstruction to achieve consistent
      parameterization across gazes. A constrained optimization problem is solved,
      which generates parametric surfaces satisfying material property constraints. The
      resultant anatomically accurate and physically meaningful models are discretized
      in the corresponding deformed material coordinates and consistent with the real
      tissue deformation. Material correspondences are provided directly. This will
      ease biomechanical simulation and inverse model parameter estimation.

PMID- 19163146
TI  - Blood vessels and feature points detection on retinal images.
AB  - In this paper we present a method for the automatic extraction of blood vessels
      from retinal images, while capturing points of intersection/overlap and endpoints
      of the vascular tree. The algorithm performance is evaluated through a comparison
      with handmade segmented images available on the STARE project database
      (STructured Analysis of the REtina). The algorithm is performed on the green
      channel of the RGB triad. The green channel can be used to represent the
      illumination component. The matched filter is used to enhance vessels w.r.t. the
      background. The separation between vessels and background is accomplished by a
      threshold operator based on gaussian probability density function. The length
      filtering removes pixels and isolated segments from the resulting image. Finally
      endpoints, intersections and overlapping vessels are extracted.

PMID- 19163145
TI  - A novel registration method for retinal images based on local features.
AB  - Sometimes it is very hard to automatically detect the bifurcations of vascular
      network in retinal images so that the general feature based registration methods
      will fail to register two images. In order to solve this problem, we developed a
      novel local feature based retinal image registration method. We first detect the
      corner points instead of bifurcations since corner points are sufficient and
      uniformly distributed in the overlaps. Second, a novel highly distinctive local
      feature is extracted around each corner point. These local features are invariant
      to rotation and contrast, and partially invariant to scaling. Third, a bilateral
      matching technique is applied to identify the corresponding features between two
      images. Finally a second order polynomial transformation is used to register two
      images. Experimental results show that our method is very robust and compute
      efficient to register retinal images even of very low quality.

PMID- 19163147
TI  - Coarse to fine segmentation of Stargardt rings using an expert guided dual
      ellipse model.
AB  - Computer aided diagnosis in the medical image domain requires adaptive knowledge
      based models to handle uncertainty, ambiguity, and noise. We propose an expert
      guided coupled dual ellipse model in a coarse to fine energy minimization
      framework. In our approach we enforce subspace model constraints by fusing domain
      knowledge and model information to guide the segmentation process on the fly. We
      apply our method to the task of retinal Stargardt segmentation a disease that
      manifests itself in a ring like structure around the macula. Quantitative
      evaluations on synthetic and real data sets show the performance of our
      framework. Experimental results demonstrate that our framework performance well
      with an area under the ROC curve of 0.93.

PMID- 19163148
TI  - Specular surface reconstruction for multi-camera corneal topographer
      arrangements.
AB  - A novel specular surface reconstruction approach developed for and used in an
      experimental multi-camera corneal topographer arrangement is presented in the
      paper. The tear-film coated, and therefore specular, corneal surface is
      mathematically reconstructed from the corneal images taken simultaneously by the
      calibrated cameras of the arrangement. The surface reconstruction is achieved by
      the joint solution of partial differential equations (PDEs) that is derived from
      the mapping between the measurement-pattern and its virtual images taken by the
      cameras. The PDEs - each given in an advantageous form for one of the cameras -
      describe the phenomenon of light-reflection at the corneal surface. The portions
      of the corneal surface that reflect - possibly different - measurement-pattern
      points to more than one camera convey starting points for the mathematical
      reconstruction of the surface.

PMID- 19163149
TI  - Retinal vessel segmentation on SLO image.
AB  - A scanning laser ophthalmoscopy (SLO) image, taken from optical coherence
      tomography (OCT), usually has lower global/local contrast and more noise compared
      to the traditional retinal photograph, which makes the vessel segmentation
      challenging work. A hybrid algorithm is proposed to efficiently solve these
      problems by fusing several designed methods, taking the advantages of each method
      and reducing the error measurements. The algorithm has several steps consisting
      of image preprocessing, thresholding probe and weighted fusing. Four different
      methods are first designed to transform the SLO image into feature response
      images by taking different combinations of matched filter, contrast enhancement
      and mathematical morphology operators. A thresholding probe algorithm is then
      applied on those response images to obtain four vessel maps. Weighted majority
      opinion is used to fuse these vessel maps and generate a final vessel map. The
      experimental results showed that the proposed hybrid algorithm could successfully
      segment the blood vessels on SLO images, by detecting the major and small vessels
      and suppressing the noises. The algorithm showed substantial potential in various
      clinical applications. The use of this method can be also extended to medical
      image registration based on blood vessel location.

PMID- 19163150
TI  - REVIEW - a reference data set for retinal vessel profiles.
AB  - This paper describes REVIEW, a new retinal vessel reference dataset. This dataset
      includes 16 images with 193 vessel segments, demonstrating a variety of
      pathologies and vessel types. The vessel edges are marked by three observers
      using a special drawing tool. The paper also describes the algorithm used to
      process these segments to produce vessel profiles, against which vessel width
      measurement algorithms can be assessed. Recommendations are given for use of the
      dataset in performance assessment. REVIEW can be downloaded from
      http://ReviewDB.lincoln.ac.uk.

PMID- 19163151
TI  - Level-set based automatic cup-to-disc ratio determination using retinal fundus
      images in ARGALI.
AB  - Glaucoma is a leading cause of permanent blindness. However, disease progression
      can be limited if detected early. The optic cup-to-disc ratio (CDR) is one of the
      main clinical indicators of glaucoma, and is currently determined manually,
      limiting its potential in mass screening. In this paper, we propose an automatic
      CDR determination method using a variational level-set approach to segment the
      optic disc and cup from retinal fundus images. The method is a core component of
      ARGALI, a system for automated glaucoma risk assessment. Threshold analysis is
      used in preprocessing to estimate the initial contour. Due to the presence of
      retinal vasculature traversing the disc and cup boundaries which can cause
      inaccuracies in the detected contours, an ellipse-fitting post-processing step is
      also introduced. The method was tested on 104 images from the Singapore Malay Eye
      Study, and it was found the results produced a clinically acceptable variation of
      up to 0.2 CDR units from the manually graded samples, with potential use in mass
      screening.

PMID- 19163152
TI  - Comparison of reflected green light and infrared photoplethysmography.
AB  - We evaluated the accuracy of pulse rate measurements obtained by reflected green
      light photoplethysmography (PPG) compared to reflected infrared light
      photoplethysmography and ECG. The wavelengths of the green and infrared light
      were 525 and 880 nm, respectively, and experiments were performed at 25 degrees C
      and at a skin temperature below 15 degrees C. The pulse rate obtained from
      reflected green light PPG was compared with the ECG RR interval and the pulse
      rate from reflected infrared PPG. The results indicated a stronger correlation
      between green PPG and ECG results at both temperatures. These results suggested
      that reflected green light PPG had an advantage over reflected infrared PPG,
      especially at temperatures below 15 degrees C.

PMID- 19163153
TI  - Calculation of ventilation threshold using noncontact respirometry.
AB  - We proposed the calculation method of the ventilation threshold using the
      noncontact respirometry under pedal stroke motion. By the simultaneous
      measurement with the expiration gas analyzer, we examined the effectiveness of
      the proposal method. There was high correlation over 0.8 between ventilation
      variations calculated by our proposed method and the expiration gas analyzer. On
      the other hand, the correlation between ventilation thresholds calculated by our
      proposed method and the expiration gas analyzer is 0.735. In this experiment, the
      sufficient examination seemed to be difficult on the correlation, since the
      difference between the systemic aerobic capacities of the examinees is small.

PMID- 19163154
TI  - Ultrasound-based coordinate measuring system for estimating cervical dysfunction
      during functional movement.
AB  - Cervical range of motion (ROM) is a part of the dynamic component of spine
      evaluation and can be used as an indication of dysfunction in anatomical
      structures as well as a diagnostic aid in patients with neck pain. Studies
      indicate that movement coordination of axial segments such as head in dynamic
      state, disrupted in pathologic conditions. In recent years, a number of non
      invasive instruments with varying degrees of accuracy and repeatability have been
      utilized to measure active or passive range of motion in asymptomatic adults. The
      aim of this investigation is to design and implement a new method by evidence
      based approach for estimating the level of defect in segment stability and
      improvement after treatment by measuring quality or quantity of movement among
      cervical segment. Transmitter sensors which have been mounted on body send
      ultrasonic burst signal periodically and from the delay time it takes for this
      burst to reach three other sensors which arranged on a T-shape Mechanical base,
      three dimensional position of the transmitter can be calculated. After sending 3D
      coordination data to a PC via USB port, a complex and elaborative Visual Basic
      software calculate the angular dispersion and acceleration for each segment
      separately. This software also calculates the stabilization parameters such as
      anchoring index (AI) and cross-correlation function (CCF) between head and trunk.

PMID- 19163155
TI  - A virtual instrument for real time in vivo measurement of carotid artery
      compliance.
AB  - A new virtual instrument for real time, non invasive measurement of carotid
      artery compliance is proposed. The instrument is a reliable, compact and low cost
      alternative to the conventional ultrasound scanner and wall tracking system for
      carotid artery compliance measurement. The measurement system uses an ultrasound
      pulse echo method to probe the carotid artery. The reflected echoes are processed
      using Hilbert transform techniques. Peak detection and echo tracking are
      implemented in LabVIEW. A comparison is done between manual and automatic method
      of echo identification. The instrument gives a display of the variation of
      carotid diameter in real time and calculates the various estimates of arterial
      compliance from the analyzed data. The capability of the instrument to accurately
      determine arterial compliance measures is demonstrated by experiments performed
      on human subjects.

PMID- 19163156
TI  - Determination of tissue type surrounding a needle tip by electrical bioimpedance.
AB  - A novel method for determining needle position based on local tissue impedance
      and electrode polarization data, is presented. Measurements of electrical
      impedance in a small volume around a needle tip can aid in determining if the
      needle is in the desired tissue. There are many possible applications for this
      technique, such as needle positioning when administering drugs in blood vessels
      or muscle tissue, for epidural analgesia or needle EMG exams.

PMID- 19163157
TI  - A high resolution, monolithic crystal, PET/MRI detector with DOI positioning
      capability.
AB  - We report on a high resolution, monolithic crystal PET detector design that
      provides depth of interaction (DOI) positioning within the crystal and is
      compatible for operation in a MRI scanner to support multimodal anatomic and
      functional imaging. Our design utilizes a novel sensor on the entrance surface
      (SES) design combined with a maximum likelihood positioning algorithm. The sensor
      will be a two-dimensional array of micro-pixel avalanche photodiodes (MAPD).
      MAPDs are a new type of solid-state photodetector with Geiger mode operation that
      can provide signal gain similar to a photomltipiler tube (PMT). In addition, they
      can be operated in high magnetic fields to support PET/MR imaging. Utilizing a
      multi-step simulation process, we determined the intrinsic spatial resolution
      characteristics of a detector using the proposed design. For a 48.8 mm by 48.8 mm
      by 15 mm LSO crystal detector readout by an 8 by 8 array of 5.8 mm by 5.8 mm MAPD
      elements the intrinsic spatial resolution is 0.83 mm FWHM in X, 0.92 mm FWHM in Y
      and 1.83 mm FWHM in Z (i.e., DOI) for normally incident photons. Comparing the
      results versus using a conventional design with the photosensors on the backside
      of the crystal, an average improvement of 25% in X, 23% in Y, and 20% in Z is
      achieved.

PMID- 19163158
TI  - Novel neuromorphic CMOS device array for biochemical charge sensing.
AB  - Novel neuromorphic CMOS device is proposed as a biochemical charge sensor. The
      basic architecture of an extended floating-gate field-effect transistor (FET) is
      modified to be suited for large-array applications. The FET has a floating-gate
      that is umbrella-shaped (UGFET), maximizing its charge sensing area in a much
      reduced transistor area. Compared to previous chemoreceptive FET-based charge
      sensors, the UGFET shows improved scalability and sensitivity. 3-D device
      simulations validate the UGFET model. The design is fabricated in a standard CMOS
      process and characterized. Experimental results on biochemical charge sensing are
      presented employing the transconductance and subthreshold measurement schemes.

PMID- 19163159
TI  - Analysis of op-amp power-supply current sensing current-mode instrumentation
      amplifier for biosignal acquisition system.
AB  - Common biosignals are frequently recorded and used in modern clinical practice
      and even daily health care applications. The most important building block of
      such an acquisition system is the analog readout front end. Usually, an
      instrumentation amplifier with high CMRR and configurable gain characteristics is
      suitable for this application. There is a current mode instrumentation amplifier
      based on op amp power supply current sensing technique, which is a possible
      solution for designing the biosignal acquisition system. This paper makes a brief
      analysis of this topology and studies some features for applying to biosignals.
      Furthermore, a real circuit simulation analysis employing CMOS 0.35 microm
      technology under a 3 V power supply is conducted.

PMID- 19163160
TI  - Relation between mouse button click duration and muscle contraction time.
AB  - Contraction and half relaxation times are important temporal measures of the
      physiological state of the muscle. We hypothesize that mouse button click
      durations may mirror muscle twitch contraction times (contraction time + half
      relaxation time). When comparing muscle twitch contraction times and mouse button
      click durations between children, adult females and adult males only small
      differences in muscle twitch contraction times were observed across these groups
      whereas large differences in mouse button click durations were measured.
      Currently, computer mice are designed using a 'one size fits all' approach and
      the results indicate that computer mouse button activation force has different
      effects on children, adult females and adult males, thus pointing towards effects
      of device design on computer mouse operation. The results indicate that it may be
      possible to evaluate the appropriateness of input device activation forces for
      different statured users by seeking activation forces where the mouse button
      click durations approximate and approach the durations of involuntary muscle
      twitches.

PMID- 19163161
TI  - The method of realizing the three-dimension positioning based on linear CCD
      sensor in general DSP chip.
AB  - Optical positioning system is an important part in the computer aided surgery
      system. Under the previous research of the three linear CCD positioning system
      prototype, this paper proposed a new way to implement three-dimensional
      coordinates reconstruction of a marker in the digital signal processor while not
      in a computer as before. And the experiments were designed to calculate the
      markers' three dimensional coordinates in the DSP chip and the computer
      respectively, the results of the three dimensional coordinates' reconstruction
      showed that the calculation precision in DSP chip and the computer had no
      difference within 0.01mm error limit. Furthermore, the method that the three
      dimensional coordinates' reconstruction implemented in the DSP chip can improve
      the stability of the optical positioning system, and to the greatest extent to
      increase the calculation independent of hardware, while not depend on computer
      processing as before.

PMID- 19163162
TI  - Heat enhances gas delivery and acoustic attenuation in CO(2) filled microbubbles.
AB  - Thermo-responsive chitosan microbubbles were developed as new therapeutic device
      for vehiculating gases to tissues concomitantly to hyperthermic treatments.
      Aiming at applications to non-invasive temperature monitoring, microbubbles were
      characterized for acoustic attenuation properties in the 1-15 MHz range both by
      direct methods and by B-mode Ultrasound imaging up to 43 degrees C, which is the
      temperature used in clinical hyperthermia. The chitosan microbubbles showed a
      mean diameter of 1 microm at room temperature, which slightly decreases after
      heating, enhancing gas delivery. Acoustic attenuation monotonically increases
      with temperature, being the extent of such variation larger than that observed in
      tissues. Both the physico-chemical and the acoustic profiles showed reversible
      variations of microbubbles approaching 43 degrees C, which might be of interest
      for applications in hyperthermic therapies.

PMID- 19163163
TI  - Design of an energy harvesting conditioning unit for hearing aids.
AB  - There is an increasing demand for giving energetic autonomy to portable and
      autonomous biomedical devices used not only by patients but common people who
      need to use the aforementioned devices. For instance, hearing aids, in order to
      be used for long time, must be connected to re-chargeable batteries in order to
      help people in case of lack of permanent electric sources. In particular, for
      audio-prosthesis, it is very interesting to extract electric energy from
      temperature or articulation movements. This paper presents some criteria of
      designing a conditioning and re-charging unit in order to convert human basal
      warmth to electric energy for audio-prosthesis; the system is based on PIC
      microcontroller that allows the managing of two temperatures: internal and
      external.

PMID- 19163164
TI  - A nonenzymatic biosensor based on copper nanoparticles modified electrode for
      detection of acetylcholine.
AB  - The electrocatalytic oxidation of acetylcholine (Ach) on copper microparticles
      modified carbon paste electrode (m-CPE) and copper nanoparticles-modified carbon
      paste electrode (n-CPE) was investigated. In the voltammogram recorded using m
      CPE, a single anodic peak related to the oxidation of ACh was observed. Using n
      CPE, however, two overlapped anodic peaks were observed. The amino acids oxidized
      on n-CPE at higher rates at lower potentials compared to m-CPE. A nonenzymatic
      amperometric biosensor was constructed and a simple analysis procedure was
      developed for the determination of ACh.

PMID- 19163165
TI  - A method for bioimpedance measure with four- and two-electrode sensor systems.
AB  - This paper presents an alternative method to measure impedances based on constant
      amplitude voltage excitation. The method makes use of feedback principle to adapt
      the measure conditions to load under test, being easily applied to bioimpedance
      measure with electrode sensors. The method has been tested for several
      frequencies and loads, employing four and two electrode setups. Results from
      electrical simulations, using CMOS circuits, fulfil the expected performance.
      This technique can be extended to wide frequency and load ranges, being an
      excellent option for impedance spectroscopy and EIT applications.

PMID- 19163166
TI  - Physiological effects of RF exposure on hypersensitive people by a cell phone.
AB  - Persons with electromagnetic hypersensitivity (EHS) complain of subjective
      symptoms such as headaches, insomnia, memory loss etc. resulting from radio
      frequency (RF) radiation by cellular phones. There have been various EHS
      provocation studies on heart rate, blood pressure, and subjective symptoms using
      GSM phones. However, there are few provocation studies on case-control study
      investigating simultaneously physiological parameters from CDMA phones. In this
      study, two volunteer groups of 18 self-declared EHS and 19 controls were exposed
      to both sham and real RF exposures by a CDMA cellular phone for half an hour
      each. We investigated the physiological parameters such as heart rates,
      respiration rates, and hear rate variability (HRV). In conclusion, the RF
      exposure by a CDMA cellular phone did not have any effects on the physiological
      parameters for both groups.

PMID- 19163167
TI  - System for unconstrained ECG measurement on a toilet seat using capacitive
      coupled electrodes : the efficacy and practicality.
AB  - Home healthcare is a common matter of concern to modern people. For the
      successful home healthcare, unconstrained bio-signal monitoring is important.
      Previously, unconstrained lavatory typed ECG measurement system was developed. It
      is enough to measure subject's ECG signal non-intrusively, but not practical
      because of moist environment of toilet. In this study, capacitive coupled
      electrode was employed for overcome above disadvantages. ECG was obtained by
      capacitive coupled electrode and compared with ECGs obtained from conventional
      Ag/AgCl electrode. Possible motion artifacts were investigated. Experimental
      results showed that toilet based capacitive coupled ECG signal was measured
      successfully.

PMID- 19163168
TI  - Unconstrained monitoring of ECG and respiratory variation in infants with
      underwear during sleep using a bed-sheet electrode unit.
AB  - An approach is proposed for obtaining both electrocardiographic potential and
      respiratory variation signal from infants lying supine with underwear during
      sleep. Capacitively coupled bed-sheet electrode unit and a methodology of
      capacitive sensing were employed to realize the approach. A pilot device was
      fabricated to explore the feasibility of the approach and evaluation experiments
      were conducted for 5 infants aged from 43 to 174 days. The results revealed that
      two outputs of the developed device synchronized respectively with the reference
      ECG and sleep breath in all experiments. The present device appears promising for
      application to bedding as an unconstrained method for ECG and respiratory
      variation monitoring of neonates or infants during sleep.

PMID- 19163169
TI  - A basic study for automatic waist circumference measurement using magnet with
      waist belt to assist obese management in daily life.
AB  - Waist circumference is a very important factor in deciding if someone has the
      potential for obesity, but there has been no device that automatically measures
      waist circumference. In this study, a new waist circumference measurable belt was
      devised and is accurate to 5mm resolution. The system is comprised of magnets and
      magneto-resistive sensors to measure waist circumference. A novel algorithm was
      developed to distinguish the belt moving direction. This belt system can assist
      in obesity and overweight management and a connection with IT and communication
      networks may make this system a more powerful tool.

PMID- 19163170
TI  - Autonomous gain verification algorithm for a dual mode digital hearing aid chip.
AB  - A dual mode digital hearing aid chip with real-time autonomous gain verifications
      algorithm is proposed and implemented. Four proposed gain models due to the
      different internal sound paths are analyzed to verify its usefulness. By adopting
      this algorithm, a real-ear aided gain and a real-ear occluded gain which
      considers internal vent effect and leakage path effect are compared with
      conventional models. To evaluate this algorithm the implemented chip adopts two
      different modes; a hearing aid mode and a gain verification mode for a hearing
      aid operation and internal gain verification, respectively. The minimum and
      maximum convergence time of the presented algorithm covers 0.05 s at a 1 kHz
      input signal and 1.6 s at a 7.5 kHz input signal, respectively. The implemented
      chip dissipates less than 130 microW at a supply voltage of 0.9 V and occupies a
      5.4 mm(2) core are at a 0.18 microm CMOS technology.

PMID- 19163171
TI  - New method for assessment of gait variability based on wearable ground reaction
      force sensor.
AB  - In this paper, a new quantitative method of analyzing gait variability using a
      developed wearable ground reaction force (GRF) sensor system is presented. The
      design of the sensor system is based on the use of five small 3-axial sensors
      distributed on the underside of a shoe, so that in human dynamics analysis this
      system can continuously measure vertical pressure force and bio-directional
      friction forces referring to anterior-posterior friction force and mediolateral
      friction force. Compared to existing spatio-temporal evaluation methods using
      traditional force plates or instrumented treadmills, the new method was developed
      based on measurements of ambulatory or wearable force sensor which can
      continuously measure ground reaction force in various environments not limited to
      the laboratory environment. The area of the center of pressure (CoP) distribution
      on the foot-plate and the average coefficient of variation of the 3-axial GRF,
      which correlate strongly with the distribution of CoP, are suggested parameters
      for quantifying gait variability. To certify the effectiveness of these
      parameters, we conducted an experimental study on a group of volunteer subjects
      who walked under a designed experimental protocol.

PMID- 19163172
TI  - SmartPad: a wireless, adhesive-electrode-free, autonomous ECG acquisition system.
AB  - During medical procedures, such as surgery, a patient's vital signs are typically
      monitored using a web of wires connected to adhesive electrodes. The large number
      of wires inhibits the medical team's access to the patient while the adhesive
      electrodes can detach, fail, or be out-of-stock, causing delays in the procedure.
      In order to combat these problems, we have developed the SmartPad: a system that
      displays a patient's electrocardiogram (ECG) signal without adhesive pads, wires,
      or active intervention from a clinician. The system automatically selects three
      electrodes from an array of Cu/Ni-fabric based electrodes patterned on a thin pad
      on which the patient lies. The selected electrodes are used to provide a
      differential 3-lead measurement of the patient's ECG, which is then transmitted
      wirelessly and displayed on a laptop computer.

PMID- 19163173
TI  - Empirical evaluation of zero-admin authentication for vital sensors in body area
      networks.
AB  - Authentication frameworks currently available in wireless networks, such as those
      in the IEEE802.15.4 security standard, are intended for applications in versatile
      sensor networks; however, both health care staff and medical professionals find
      it difficult to set them up. In addition, it is expected that these frameworks
      will increase computational burdens when applied to small vital sensors. It is
      therefore necessary to devise security arrangements that are easy to setup and
      consume less power for body area networks (BANs) consisting of vital sensors. In
      this paper, we evaluate our proposed zero-admin authentication system with
      reduced computational burden on a real vital sensor that has limited RAM/ROM and
      CPU power with a light-weight battery. Our proposed system expects a re-keying
      mechanism using vital data suitable for small sensors and uses one-way wireless
      communication for re-keying. The keys are kept their strength by infrequent
      updates of users' conditions. We discuss the protocol and then evaluate the re
      keying mechanism with a typical cryptography on the real sensor device. Our
      evaluation shows the effectiveness of the proposed authentication system for
      practical use and raises additional issues that must be resolved for improved
      performance.

PMID- 19163174
TI  - Data acquisition system using six degree-of-freedom inertia sensor and ZigBee
      wireless link for fall detection and prevention.
AB  - Fall detection and prevention require logged physiological activity data of a
      patient for a long period of time. This work develops a data acquisition system
      to collect motion data from multiple patients and store in a data base. A
      wireless sensor network is built using high precision inertia sensors and low
      power Zigbee wireless transceivers. Testing results prove the system function
      properly. Researchers and physicians can now retrieve and analyze the accurate
      data of the patient movement with ease.

PMID- 19163175
TI  - Human computer interaction using hand gesture.
AB  - Hand gesture is a very natural form of human interaction and can be used
      effectively in human computer interaction (HCI). This project involves the design
      and implementation of a HCI using a small hand-worn wireless module with a 3-axis
      accelerometer as the motion sensor. The small stand-alone unit contains an
      accelerometer and a wireless Zigbee transceiver with microcontroller. To minimize
      intrusiveness to the user, the module is designed to be small (3cm by 4 cm). A
      time-delay neural network algorithm is developed to analyze the time series data
      from the 3-axis accelerometer. Power consumption is reduced by the non-continuous
      transmission of data and the use of low-power components, efficient algorithm and
      sleep mode between sampling for the wireless module. A home control interface is
      designed so that the user can control home appliances by moving through menus.
      The results demonstrate the feasibility of controlling home appliances using hand
      gestures and would present an opportunity for a section of the aging population
      and disabled people to lead a more independent life.

PMID- 19163176
TI  - A novel ECG telemetry and monitoring system based on Z-Wave communication.
AB  - This paper presents a novel ECG telemetry system based on Z-Wave communication
      protocol. The proposed system consists of small portable devices that acquire,
      compress and transmit the ECG to a RF-USB interface connected to a central
      monitoring computer. The received signals are filtered, QRS complexes and P and T
      waves are localized, and different waveforms are classified in order to be able
      to provide diagnosis tools like heart rate variability and turbulence analysis.
      Due to the limitation of communication bandwidth, the maximum number of measuring
      devices connected to a central monitor is four. The proposed system composed of
      inexpensive components can serve as flexible alternative to current ECG
      monitoring systems.

PMID- 19163177
TI  - 3D electrode localization on wireless sensor networks for wearable BCI.
AB  - This paper presents a solution for electrode localization on wearable BCI radio
      enabled electrodes. Electrode positioning is a common issue in any electrical
      physiological recording. Although wireless node localization is a very active
      research topic, a precise method with few centimeters of range and a resolution
      in the order of millimeters is still to be found, since far-field measurements
      are very prone to error. The calculation of 3D coordinates for each electrode is
      based on anchorless range-based localization algorithms such as Multidimensional
      Scaling and Self-Positioning Algorithm. The implemented solution relies on the
      association of a small antenna to measure the magnetic field and a
      microcontroller to each electrode, which will be part of the wireless sensor
      network module. The implemented solution is suitable for EEG applications, namely
      the wearable BCI, with expected range of 20 cm and resolution of 5 mm.

PMID- 19163178
TI  - iSANLA: intelligent sensor and actuator network for life science applications.
AB  - In the fields of neurological rehabilitation and neurophysiological research
      there is a strong need for miniaturized, multi channel, battery driven, wireless
      networking DAQ systems enabling real-time digital signal processing and feedback
      experiments. For the scientific investigation on the passive auditory based 3D
      orientation of Barn Owls and the scientific research on vegetative locomotor
      coordination of Parkinson's disease patients during rehabilitation we developed
      our 'intelligent Sensor and Actuator Network for Life science Application'
      (iSANLA) system. Implemented on the ultra low power microcontroller MSP430 sample
      rates up to 96 kHz have been realised for single channel DAQ. The system includes
      lossless local data storage up to 4 GB. With its outer dimensions of 20mm per rim
      and less than 15 g of weight including the Lithium-Ion battery our modular
      designed sensor node is thoroughly capable of up to eight channel recordings with
      8 kHz sample rate each and provides sufficient computational power for digital
      signal processing ready to start our first mobile experiments. For wireless
      mobility a compact communication protocol based on the IEEE 802.15.4 wireless
      standard with net data rates up to 141 kbit/s has been implemented. To merge the
      lossless acquired data of the distributed iNODEs a time synchronization protocol
      has been developed preserving causality. Hence the necessary time synchronous
      start of the data acquisition inside a network of multiple sensors with a
      precision better than the highest sample rate has been realized.

PMID- 19163179
TI  - Embedded instrumentation for skin admittance measurement.
AB  - Skin admittance measurements are used in several biomedical applications, and the
      technology available today opens for new design solutions. The digital
      instrumentation has several advantages to the conventional analog instrumentation
      by needing fewer components, having lower cost, better reliability and is easier
      to modify in the field. A design alternative is presented which uses an 8-bit
      microcontroller and few extra components for skin admittance instrumentation.
      Most of the measuring tasks are handled digitally in software by using a point-by
      point routine allowing continuous conductance and susceptance measurements with
      low processor usage. The design is best suited for low-frequency measurement
      instrumentation where small size and low cost of the instrument is required.

PMID- 19163180
TI  - Basic study on indoor location estimation using Visible Light Communication
      platform.
AB  - A VLC (Visible Light Communication) system using fluorescent lights has been
      developed for indoor guidance of the visually impaired. While it is relatively
      straightforward to provide generalized location information for a blind user,
      precise location information is much more difficult to determine. We propose that
      the effective data reception range and the receiver's precise location can be
      calculated using measured sensor angles. A series of experiments have been
      performed in a practical platform with 22 fluorescent lights, 39 measuring points
      (MP). The average distance error could reach as low as 10 cm. This development
      will provide greater accuracy and therefore less stress for blind users.

PMID- 19163181
TI  - Fabrication and characterization of microwave immunosensors based on organic
      semiconductors with nanogold-labeled antibody.
AB  - Microelectronic biosensors hold great promise for rapid, sensitive and specific
      in vitro point-of-care immunodiagnostics. In particular, sensors fabricated using
      organic semiconductors have attractive advantages-such as ease of manufacture and
      low cost-in the design and implementation of such devices. Furthermore,
      immobilization of an antibody or protein antigen as a biorecognition element onto
      an organic semiconducting film allows for direct transduction of biomolecular
      binding events into an electronic signal which is readily measured and processed.
      In previous work, we have demonstrated that an antigen can be bound to organic
      semiconducting films while retaining enzymatic activity after immobilization. The
      present work considers organic semiconducting films which are spin-cast onto an
      interdigitated electrode; antibodies labeled with gold-nanoparticles are applied
      to the organic semiconducting film and serve as a biorecognition element. The
      sensor geometry includes a high-frequency coplanar waveguide contact
      metallization to facilitate direct measurement using microwave wafer probes.
      Equivalent circuit models are derived from microwave measurements over the
      frequency range 0.3 MHz to 8.5 GHz.

PMID- 19163182
TI  - In vitro magnetic stimulation of unmyelinated nerves.
AB  - Magnetic stimulation of neural tissue is an intriguing technology because
      excitation may be affected without a direct interface between the stimulator and
      the tissue. Current methods of magnetic stimulation use large air core coils,
      limiting the size of the neural preparations available for study. We use ferrite
      cores to reduce the stimulation area. Scaling allows the use of unmyelinated
      neural preparations with a range of space and length constants. Results are shown
      using two well studied neural preparations under varying test conditions.

PMID- 19163183
TI  - A low-power, low-noise neural-signal amplifier circuit in 90-nm CMOS.
AB  - A fully-differential low-power low-noise preamplifier for biopotential and neural
      recording applications is presented. This design, which has been simulated in a
      standard 90-nm CMOS process, consumes 30 microW from a 3-V power supply. The
      simulated integrated input-referred noise is 2.3 microV over 0.1 Hz to 20 kHz.
      The amplifier also provides an output swing of +/- 0.9 V with a THD of less than
      0.1%

PMID- 19163184
TI  - Development of a microcontrolled bioinstrumentation system for active control of
      leg prostheses.
AB  - This article describes the design of a microcontrolled bioinstrumentation system
      for active control of leg prostheses, using 4-channel electromyographic signal
      (EMG) detection and a single-channel electrogoniometer. The system is part of a
      control and instrumentation architecture in which a master processor controls the
      tasks of slave microcontrollers, through a RS-485 interface. Several signal
      processing methods are integrated in the system, for feature extraction
      (Recursive Least Squares), feature projection (Self Organizing Maps), and pattern
      classification (Levenberg-Marquardt Neural Network). The acquisition of EMG
      signals and additional mechanical information could help improving the precision
      in the control of leg prostheses.

PMID- 19163185
TI  - Real-time signal processing of accelerometer data for wearable medical patient
      monitoring devices.
AB  - Elderly and other people who live at home but required some physical assistance
      to do so are often more susceptible injury causing falls in and around their
      place of residence. In the event that a fall does occur, as a direct result of a
      previous medical condition or the fall itself, these people are typically less
      likely to be able to seek timely medical help without assistance. The goal of
      this research is to develop a wearable sensor device that uses an accelerometer
      for monitoring the movement of the person to detect falls after they have
      occurred in order to enable timely medical assistance. The data coming from the
      accelerometer is processed in real-time in the device and sent to a remote
      monitoring station where operators can attempt to make contact with the person
      and/or notify medical personnel of the situation. The ADXL330 accelerometer is
      contained within a Nintendo WiiMote controller, which forms the basis of the
      wearable medical sensor. The accelerometer data can then be sent via Bluetooth
      connection and processed by a local gateway processor. If a fall is detected, the
      gateway will then contact a remote monitoring station, on a cellular network, for
      example, via satellite, and/or through a hardwired phone or Internet connection.
      To detect the occurrence of ta fall, the accelerometer data is passed through a
      matched filter and the data is compared to benchmark analysis data that will
      define the conditions that represents the occurrence of a fall.

PMID- 19163186
TI  - Maximum likelihood methods in biology revisited with tools of computational
      intelligence.
AB  - We investigate the problem of identification of genes correlated with the
      occurrence of diseases in a given population. The classical method of parametric
      linkage analysis is combined with newer tools and results are achieved on a model
      problem. This traditional method has advantages over non-parametric methods, but
      these advantages have been difficult to realize due to their high computational
      cost. We study a class of Evolutionary Algorithms from the Computational
      Intelligence literature which are designed to cut such costs considerably for
      optimization problems. We outline the details of this algorithm, called Particle
      Swarm Optimization, and present all the equations and parameter values we used to
      accomplish our optimization. We view this study as a launching point for a wider
      investigation into the leveraging of computational intelligence tools in the
      study of complex biological systems.

PMID- 19163187
TI  - Detecting trunk motion changes due to pregnancy using pattern recognition
      techniques.
AB  - There are anatomical changes during pregnancy due to the increased and altered
      mass distribution in the trunk that could lead to changes in gait. There is
      little research, however, regarding adaptations in trunk motion with pregnancy.
      In this paper, we investigated the application of two pattern recognition
      techniques: support vector machine (SVM) and linear discriminant analysis (LDA)
      to detect differences in trunk kinematics, when walking, between women in late
      pregnancy and nulliparous (control) women. Test results indicate that the SVM can
      identify the trunk motion of pregnant women from their counterparts with a better
      accuracy compared to the LDA (71.43% vs 28.57% respectively). Furthermore, with a
      feature selection technique applied, the accuracy improved to 95.24% % using only
      2 features namely the pelvic sagittal plane displacement and thoracic lateral
      tilt displacement at heel contact. The results suggest that for better detection
      of trunk motion changes in pregnant women, non-linear analysis may be required.
      The SVM was able to effectively differentiate pregnancy related trunk motion
      changes during a walking task which may indicate altered musculoskeletal loads
      with potential for injury or pain.

PMID- 19163188
TI  - Improvement of touch sensitivity by pressing.
AB  - It is really interesting to know how a blood flow has an influence on a touch
      sensitivity during human fingertip exploration over an environment. In this
      paper, we examine experimentally how the touch sensitivity is changed under the
      condition that the blood flow is interrupted compulsorily by pressing the
      proximal phalange of human finger. Through the weight discrimination test based
      on Weber's Law, we found that the touch sensitivity improves temporarily with the
      statistical significance test of below 0.1 %, when a finger proximal phalange is
      bound and pressed. Experimental results also show that there exists a meaningful
      correlationship between the stiffness of fingertip and the touch sensitivity.

PMID- 19163189
TI  - Using an in silico liver to evaluate a hepatic enzyme induction mechanism.
AB  - Will enzyme induction (EI) within different hepatic lobular zones, following
      initial exposure to a single xenobiotic, be homogeneous or heterogeneous? Wet-lab
      EI experiments, as formulated, are infeasible. The In Silico Liver (ISL) was
      designed in part to explore plausible answers to such questions. The ISL is
      synthetic, physiologically based, fine-grained, and multi-agent. It has been
      validated against in situ drug disposition data. Results from simulation
      experiments falsified the hypothesis that a uniform distribution of simulated
      drug passing through an ISL will produce uniform EI. The results may have a
      hepatic counterpart. We discuss methodological considerations regarding multi
      level observation and manipulation of livers and this new class of models.

PMID- 19163190
TI  - Tissue-specific RMA models to incrementally normalize Affymetrix GeneChip data.
AB  - Gene expression classifiers have been used to predict diagnosis of disease,
      patient prognosis and patient response to therapy. Although there have been
      remarkable successes in this area, a particular goal of personalized medicine is
      the ability predict a response from a single gene expression microarray. One
      aspect of this problem is the normalization of microarrays. Affymetrix GeneChip
      microarrays are typically processed using model-based algorithms that require all
      of the data in order to adequately estimate the model. We experiment with the RMA
      normalization procedure in an incremental fashion, adding new chips to an
      existing normalization model. Focusing on tissue-specific normalization models,
      we generate datasets that have very small differences from a batch normalization.
      Through several large datasets of patient samples, we provide evidence that RMA
      models of normalization converge to a common model in homogenous samples. These
      results offer the promise of maintaining large data warehouses of patient
      microarray samples without the requirement of constant renormalization.

PMID- 19163191
TI  - An interactive visualization tool and data model for experimental design in
      systems biology.
AB  - Experimental design is important, but is often under-supported, in systems
      biology research. To improve experimental design, we extend the visualization of
      complex sphingolipid pathways to study biosynthetic origin in SphinGOMAP. We use
      the ganglio-series sphingolipid dataset as a test bed and the Java Universal
      Network / Graph Framework (JUNG) visualization toolkit. The result is an
      interactive visualization tool and data model for experimental design in lipid
      systems biology research. We improve the current SphinGOMAP in terms of
      interactive visualization by allowing (i) choice of four different network
      layouts, (ii) dynamic addition / deletion of on-screen molecules and (iii) mouse
      over to reveal detailed molecule data. Future work will focus on integrating
      various lipid-relevant data systematically i.e. SphinGOMAP biosynthetic data,
      Lipid Bank molecular data (Japan) and Lipid MAPS metabolic pathway data (USA). We
      aim to build a comprehensive and interactive communication platform to improve
      experimental design for scientists globally in high-throughput lipid systems
      biology research.

PMID- 19163192
TI  - Interactive reference descriptions of cellular electrophysiology models.
AB  - With the advent and popularization of technologies such as CellML and SBML it has
      become relatively easy to share and exchange mathematical models of biological
      systems. However, as such technology evolves it is inevitable that not all tools
      will correctly interpret the full range of models able to be described. It is
      also necessary to completely describe the mathematical models allowing model
      users to appropriately use each model. To address these issues we have previously
      developed methods and tools based on community defined standards which allow for
      the specification of a reference description of a mathematical model. Such
      reference descriptions provide a comprehensive description of both the
      mathematical model and the outcomes expected when performing specific numerical
      simulations using the model. Thus providing for quantitative validation of tool
      interpretation of a given model as well as informing the model user as to all
      aspects of the model definition. Further development of this work has led to the
      conclusion that presenting such reference descriptions in a user friendly and
      interactive manner provides a powerful tool for the dissemination and
      understanding of the mathematical model. Furthermore, such a tool is seen as an
      invaluable teaching aid in the education of biomedical engineers and scientists
      allowing for anything from a superficial to a very comprehensive interaction with
      the mathematical model.

PMID- 19163193
TI  - Portable sensor based dynamic estimation of human oxygen uptake via nonlinear
      multivariable modelling.
AB  - Noninvasive portable sensors are becoming popular in biomedical engineering
      practice due to its ease of use. This paper investigates the estimation of human
      oxygen uptake (VO(2)) of treadmill exercises by using multiple portable sensors
      (wireless heart rate sensor and triaxial accelerometers). For this purpose, a
      multivariable Hammerstein model identification method is developed. Well designed
      PRBS type of exercises protocols are employed to decouple the identification of
      linear dynamics with that of nonlinearities of Hammerstein systems. The support
      vector machine regression is applied to model the static nonlinearities.
      Multivariable ARX modelling approach is used for the identification of dynamic
      part of the Hammerstein systems. It is observed the obtained nonlinear
      multivariable model can achieve better estimations compared with single input
      single output models. The established multivariable model has also the potential
      to facilitate dynamic estimation of energy expenditure for outdoor exercises,
      which is the next research step of this study.

PMID- 19163194
TI  - Oesophageal techniques for deriving the lung dynamics of quietly breathing sheep.
AB  - An airway monitoring system was developed to record the lung dynamics of sheep
      using oesophageal pressure techniques. These techniques are minimally invasive
      and do not impede the animal from breathing spontaneously. This study
      investigates three methods for deriving lung resistance (R) and compliance (C) by
      evaluating their ability to select regular breaths amongst artefact effected
      signals. The Multi Linear Regression method, the Modified Mead-Whittenberger
      (MMW) method and Isovolumetric method were tested against signals with movement
      and/or swallowing artifacts. Their coefficient of variation (% CV) revealed that
      the MMW had the least variation with R at 35% CV and C at 25 % CV. The lung
      dynamics for 14 quietly breathing sheep were R = 1.5 +/- 0.5 cmH2O/l/s, C = 0.20
      +/- 0.08 l/cmH2O, tidal volume = 0.25 +/- 0.05 litres and respiratory rate = 26
      +/- 6 bpm.

PMID- 19163195
TI  - Characterization of inspiratory flow limitation during sleep with an exponential
      model.
AB  - Assessing incidence and severity of inspiratory flow limitation (IFL) is of
      importance for patients suffering of sleep disordered breathing (SDB) in order to
      diagnose a spectrum of different pathologies. In this study a new exponential
      equation is proposed to characterize the pressure/flow relationship of IFL and
      non-IFL breaths. Classical and alternative criteria are applied on the model's
      predictions in order to assess IFL, and its outcome is compared to the outcome of
      other models. The newly proposed exponential model seems to be promising, as it
      outperforms other models by achieving a global average sensitivity of 93% and
      specificity of 91%, and the lowest mean square error when estimating resistance
      at peak pressure. Additional statistical tests were performed on the exponential
      model's coefficients in order to determine if a coefficient based classification
      is possible.

PMID- 19163196
TI  - Impulse oscillometric features of lung function: towards computer-aided
      classification of respiratory diseases in children.
AB  - Asthma is the most prevalent chronic respiratory disease in children. Reliable
      and patient-friendly instruments and methods are required to help pulmonologists
      accurately detect asthma with acceptable clinical accuracy, specificity and
      sensitivity. Impulse Oscillometry System (IOS) based on the Forced Oscillation
      Technique (FOT) has been successfully used to measure lung function in children
      with a high degree of sensitivity and specificity to small airway dysfunction
      (SAD). IOS measures the mechanical impedance of the respiratory system.
      Equivalent electrical circuit models of lung function have been developed that
      can be used to quantify severity of SAD. It has been shown that impulse
      oscillometric parameters as well as parameter estimates of these electrical
      models provide useful indicators of lung function and therefore have the
      potential to be used as sensitive features for computer-aided classification of
      pulmonary function in health and disease.

PMID- 19163197
TI  - High frequency chest compression effects on cardio-respiratory interaction.
AB  - In this study, we present a quantitative approach to the analysis of the HFCC
      effect on heart rate changes in the respiratory stage according to different
      pulsation conditions with HFCC pulsation and without HFCC pulsation. We have
      shown that the heart rate increases with higher pressure settings revealing
      different patterns depending on the respiration stages. For our interaction study
      of how the heart and lungs were affected by HFCC, phase synchronization was
      considered and compared under different conditions which determine the real
      biological phenomenon for nonlinear or linear oscillatory coupling. The subject
      for this study was young and healthy, so these preliminary results should be
      verified with more detailed studies from abundant subjects to increase HFCC
      efficacy for lung disease patients. Interestingly, the indication or tracking of
      heart rate changes, respiration rate changes, or synchronization epoch can be the
      standard index for how much the cardiac and respiratory system improve using HFCC
      during therapy time or after therapy time.

PMID- 19163198
TI  - The benefit of stretching along the artery.
AB  - Many rehabilitation exercises involve the stretching of bodies. We point out the
      necessity of the longitudinal stretching in arteries. The efficiency of an
      arterial system is closely related to the condition of the transverse vibration
      of the arterial walls or to the magnitudes of the area oscillation in all blood
      vessels. For a given blood pressure wave, a more elastic arterial wall has larger
      area oscillation, and therefore a higher efficiency in circulation. Elastic
      properties of the artery depend on the longitudinal stretching. In vitro
      experiment on pig aorta confirms that proper longitudinal stretching increases
      its elasticity and benefits to the circulatory system.

PMID- 19163199
TI  - A study on characteristics of radial arteries through ultrasonic waves.
AB  - The study aims to measure and analyze the thickness and depth of blood vessel on
      the pulse diagnosis locations (CHON, KWAN, CHUCK) and the blood velocity through
      the use of ultrasonic waves (LOGIQ5PRO, GE Medical, U.S.) in order to understand
      the structural difference of pulse diagnosis locations. The subjects included 44
      healthy men and women (22.28+/-2.62 age) considered normal in terms of Body Mass
      Index (BMI). The thickness and depth of the blood vessel and the blood velocity
      were measured three times on CHON, KWAN and CHUCK to obtain the average value.

PMID- 19163200
TI  - Stochastic resonance can induce oscillation in a recurrent Hodgkin-Huxley neuron
      model with added Gaussian noise.
AB  - Stochastic resonance (SR) has been shown to enhance the signal to noise ratio or
      detection of signals in neurons. It has not been clear yet if SR can play an
      important role in information processing in neural networks. In this paper, we
      test the hypothesis through computer simulations that SR can induce an
      oscillation phenomenon in a recurrent neural network with added Gaussian noise in
      which the recurrent model is constructed by four Hodgkin-Huxley (HH) neuron
      models. Each HH neuron model is driven by Gaussian noise and sub-threshold
      excitatory synaptic currents with an alpha function from another HH neuron model,
      and the action potentials (spike firings) of each HH neuron model are transferred
      to the other HH neuron model via sub-threshold synaptic currents. From spike
      firing times recorded, the inter spike interval (ISI) histogram was generated,
      and the periodicity of spike firings was detected from the ISI histogram at each
      HH neuron model. The results show that the probability of spike firings in the
      oscillation period (about 50 ms or 20 Hz) increases as the standard deviation
      (S.D.) of the Gaussian white noise increases, and reach a maximum value at a
      specific S.D. of the Gaussian white noise, implying that SR can improve sub
      threshold synaptic transmission in the recurrent HH neuron model. It is concluded
      that an oscillation (20 Hz) can be induced by adding Gaussian white noise at
      lower amplitudes with intrinsic characteristics in the recurrent HH neuron model,
      while another oscillation (100 Hz) can be generated by the noise at greater
      amplitudes with extrinsic characteristics.

PMID- 19163201
TI  - Inhibitory chemical coupling of electronic Morris-Lecar neuron model and its
      bifurcation analysis.
AB  - In this paper, we got the implementation of the electronic neuron based on the
      Morris-Lecar model, and use the circuit to analysis the bifurcation of the Morris
      Lecor model. Based on the results of the bifurcation analysis, we get bursting
      neurons by introducing a slow driving current. Furthermore, based on the
      implementation of a single electronic neuron, the electronic neurons are coupled
      through inhibiting chemical synapses which is one of the most important
      connections. Finally, we analyze behavior of the network of the electronic
      neurons coupled through the inhibiting chemical synapses.

PMID- 19163202
TI  - Comparison of electrically-evoked ganglion cell responses in normal and
      degenerate retina.
AB  - Retinal prosthesis is regarded as a promising method for restoring vision for the
      blind with retinal diseases such as retinitis pigmentosa (RP) and age related
      macular degeneration (ARMD). Among the several prerequisites for retinal
      prosthesis to succeed, one of the most important factors is the optimization of
      electrical stimulation applied through the prosthesis. From the previous study,
      we showed that the electrical characteristics of diseased retina are different
      from those of normal retina. For the next step, we compared electrically evoked
      response properties of retinal ganglion cells and established the thresholds for
      charge density in normal and rd1 mouse using multi-electrode array (MEA). The
      threshold for charge density was higher in rd1 mouse. The mean values were 254.78
      microC/cm(2) and 424.62 microC/cm(2) in normal and rd1 mouse, respectively.

PMID- 19163203
TI  - Nonparametric modeling of single neuron.
AB  - Nonlinear dynamic models were built with Volterra Lagurre kernel method to
      characterize the input-output properties of single hippocampal CA1 pyramidal
      neurons. Broadband Poisson random impulse trains with a 2 Hz mean frequency,
      which include the majorities of the spike patterns in behaving rats, were used to
      stimulate the Schaffer collaterals. Corresponding random-interval post-synaptic
      potential (PSP) and spike train data were recorded from the cell bodies using
      whole-cell recording technique and then analyzed with the nonlinear dynamic
      model. The model consists of two major components, i.e., a feedforward three
      order Volterra kernel model characterizing the transformation of presynaptic
      stimulations to pre-threshold PSPs, and a feedback one order Volterra kernel
      model capturing the spike-triggered after-potential. Results showed that the
      model could predict 1) the sub-threshold PSPs trace with a normalized mean square
      error around 10% and 2) the spikes with accuracy higher than 80%.

PMID- 19163204
TI  - An integrative multiscale modeling approach for the study of tinnitus
      decompensation neural correlates.
AB  - The study of tinnitus has become of great interest due to the increasing number
      and severity of cases reported worldwide. To cope with such situation, many
      experimental and theoretical studies have been dedicated to gain deeper insight
      into the neurophysiological mechanisms involved in the tinnitus decompensation.
      In this direction, some of the most influential tinnitus models have emphasized
      the link between selective attention and the tinnitus decompensation. However, it
      is still not clear what are the mechanisms involved in such relation and wether
      it is possible to provide a neuropsychological framework linking them with
      respect to large-scale neural correlates. In order to address such issues, we
      make use of evoked cortical potential neural correlates of auditory selective
      attention. We thus propose an integrative multiscale modeling approach for large
      scale neural correlates of selective attention in the tinnitus decompensation.
      The results of our simulations are compared with experimental data so that
      hypothesis can be validated.

PMID- 19163205
TI  - Effects of an improved auditory-periphery model on the response properties of
      modeled neurons in the dorsal cochlear nucleus.
AB  - Dorsal Cochlear Nucleus (DCN) neurons were simulated using two different models
      of auditory nerve (AN) fibers as inputs, the Carney model [1] and the Zilany &
      Bruce model [2], [3]. The change of AN models produced very different responses.
      DCN neurons simulated using the Zilany and Bruce model had much greater regions
      of excitation and significantly reduced regions of inhibition. Further
      investigation into the differences between the two AN models revealed that the
      broadened tuning of the auditory nerve fibers produced by the Zilany & Bruce
      model at higher stimulus intensities coupled with the lower excitation thresholds
      accounted for the discrepancies. Changes in DCN model connection parameters and
      their effects on the resulting simulated neurons were then explored in an attempt
      to provide a qualitative framework for determining a set of DCN parameters
      capable of reproducing physiological responses using the Zilany and Bruce AN
      fiber model. A mix of increased W-cell inhibition to narrow the response of type
      II cells and changes in AN connection parameters to increase their excitability
      at higher intensities were found to be required to reproduce physiological
      response properties. These changes in the type-II cell response would provide
      adequate compensation for the increased excitation and broadened responses at
      higher intensities observed in DCN model P-cells.

PMID- 19163206
TI  - Fixed threshold modeling of an adjustable threshold integrate-and-fire neuronal
      model.
AB  - An action potential is generated when the membrane potential of a spiking neuron
      reaches a certain threshold. Although it is well-known that the threshold level
      of a neuron is not a fixed value and changes with time and neuronal parameters,
      its variation is often ignored in neuronal modeling due to the complexity of the
      analysis. Assuming a fixed threshold level, however, may produce non-realistic
      results. If we find a model to incorporate the impact of the variation of the
      threshold in a fixed threshold model we can benefit from the simplicity of the
      existing fixed-threshold models yet obtain more realistic results. It is shown
      here that, with some approximations, we can create a fixed threshold model for an
      integrate-and-fire neuronal model from an adjustable threshold model by some
      simple operations. Both models generate the same spike (action potential)
      pattern.

PMID- 19163207
TI  - Global synchronization of N neurons in external electrical stimulation via active
      control.
AB  - In this paper, active control law is derived and applied to control and
      synchronize N(N >or= 3) unidirectional coupled Fitzhugh-Nagumo neurons in
      external electrical stimulation. Firstly, the dynamical behavior of the nonlinear
      Fitzhugh-Nagumo model responding to various external electrical stimulations is
      studied. Then, using the results of the analysis, the active control strategy is
      designed for global synchronization of the N(N >or= 3) unidirectional coupled
      neurons and stabilizing the chaotic trajectory of the slave system to desired
      periodic orbit of the master system. Numerical simulations demonstrate the
      validity and feasibility of the proposed method.

PMID- 19163208
TI  - Control of an unstable load using visual feedback.
AB  - Joint stiffness defines the dynamic relationship between the position of the
      joint and the torque acting about it. Joint stiffness is viewed as consisting of
      two components: reflex and intrinsic stiffness. However, when subjects attempt to
      maintain the position of a joint constant, such as in upright stance, voluntary
      torque will contribute to the measured joint stiffness. This voluntary torque may
      arise from visual, vestibular and proprioceptive sources. In this study, subjects
      were given the task of maintaining the position of a large inertial load
      constant, using only visual feedback. We found that subjects produced torques
      which were delayed, low-pass filtered versions of the load velocity. We also
      showed that the use of velocity information is critical, because it is not
      possible to stabilize the system without it.

PMID- 19163209
TI  - The proposal of the locomotive system for capsule endoscopes.
AB  - The capsule endoscope authorized in some countries in late years has the
      advantage of preparing the observation in difficult small intestines in a past
      endoscope. However, because the promotion mechanism of a capsule endoscope
      depends only on the peristaltic motion of a digestive organ, the oversight of
      change to a morbid state is feared. Authors aim at the achievement of a free
      movement and remote diagnoses in small intestines, and are developing a
      locomotive system for capsule endoscopes. This paper describes the proposal of
      the locomotive system with an electromagnetic actuator, and examination of a
      simulation model for this locomotive system.

PMID- 19163211
TI  - A novel endoscopic delivery system for placement of a duodenal-jejunal implant
      for the treatment of obesity and type 2 diabetes.
AB  - The EndoBarrier Delivery System is a unique product capable of reliably
      delivering an implant into the small intestine. Further improvements to the
      product can likely be made to facilitate tracking and improved navigation through
      the small bowel. This unique system and its related technology may have
      additional applications where access to the small bowel is desired such as drug
      delivery, diagnostic and therapeutic endoscopy and small bowel stent delivery.

PMID- 19163210
TI  - Interventional procedure based on nanorobots propelled and steered by flagellated
      magnetotactic bacteria for direct targeting of tumors in the human body.
AB  - Flagellated bacteria used as bio-actuators may prove to be efficient propulsion
      mechanisms for future hybrid medical nanorobots when operating in the
      microvasculature. Here, we briefly describe a medical interventional procedure
      where flagellated bacteria and more specifically MC-1 Magnetotactic Bacteria
      (MTB) can be used to propel and steer micro-devices and nanorobots under computer
      control to reach remote locations in the human body. In particular, we show
      through experimental results the potential of using MTB-tagged robots to deliver
      therapeutic agents to tumors even the ones located in deep regions of the human
      body. We also show that such bacterial nanorobots can be tracked inside the human
      body for enhanced targeting under computer guidance using MRI as imaging
      modality. MTB can not only be guided and controlled directly towards a specific
      target, but we also show experimentally that these flagellated bacterial
      nanorobots can be propelled and steered in vivo deeply through the interstitial
      region of a tumor. The targeting efficacy is increased when combined with larger
      ferromagnetic micro-carriers being propelled by magnetic gradients generated by a
      MRI platform to carry and release nanorobots propelled by a single flagellated
      bacterium near the arteriocapillar entry. Based on the experimental data obtained
      and the experience gathered during several experiments conducted in vivo with
      this new approach, a general medical interventional procedure is briefly
      described here in a biomedical engineering context.

PMID- 19163212
TI  - Thermal effect of sonophoresis for accelerating the analgesic effect of local
      anesthetics on rat tail nerve.
AB  - Sonophoresis is an ultrasound transdermal drugs delivery system. The eutectic
      mixture of local anesthetics (EMLA) has been used clinically for anesthesia but
      requires at least one hour to take effect and lacks of analgesia's objective
      assessment. We proposed that sonophoresis could reduce the duration of EMLA
      analgesia effect onset and be assessed by sensory conduction studies. Thirty
      Wistar adult rats were randomized into normal, control, ultrasound-, and heat
      treatment groups. Normal group was received no EMLA cream or ultrasound and heat
      treatment. The control group received the EMLA cream on the rat tail at 3.5 cm
      distal to the rat tail base for local anesthesia of tail nerve. Ultrasound- and
      heat-treatment groups were received ultrasound with different parameters and heat
      treatment, respectively, before EMLA cream applied. Sensory conduction studies of
      tail nerve were made before and after treatment every 5 min at least for 60 min
      in all rats. There was no significant difference between the EMLA control group
      and heat treatment group. All rats in ultrasound-treatment group exhibit
      significant difference with EMLA control group and heat-treatment group in time
      for decreased 20% SNCV except for the 2 W/cm(2), 25 min, 20% in ultrasound
      treatment group having no significant difference with heat-treatment group. There
      was no significant difference between ultrasound-treatment subgroups. In the
      decrease of amplitude, only the 2 W/cm(2), 5 min, 100% and the 2 W/cm(2), 10 min,
      50% in ultrasound-treatment group had significant difference between EMLA control
      and heat-treatment groups. We have objectively examined the sonophoresis effect
      of ultrasound by investigating the effects of EMLA. Applying ultrasound for 5 min
      reduces the onset time of EMLA analgesia from 60 min to less than 20 min.
      Ultrasound sonophoresis of analgesic drugs is potentially useful in the treatment
      of carpal tunnel syndrome, tooth extraction, and other applications of analgesia.

PMID- 19163213
TI  - Development of CMTD (Curved Multi-Tubed Device) -system III and its application
      to the needle-insertion for liver.
AB  - The purpose of this study is to realize the mechanically-controllable needle
      insertion system using the CMTD (Curved Multi-Tube Device) which was developed by
      Furusho Laboratory. A CMTD, was developed for minimally-invasive surgery and
      needle insertion. And we use ultrasonograph as a sensing device to detect the
      position of bible duct or tumor and the orientation and position of the needle
      which is inserted into liver. This system makes safe minimally-invasive surgery
      possible, because all complex mechanisms are arranged outside of the body.

PMID- 19163214
TI  - Breath-figure polymer films with local microporosity controlled via spatio
      thermal templating.
AB  - Porous structures offer a vast range of important industrial applications. In the
      context of medicine, and specifically in the area of controlled drug delivery,
      spatial [and temporal] control over local porosity has a significant influence on
      net molecular flux through [membrane-based] controlled release platforms. Such
      systems may be formulated as oral, transdermal, or even implantable entities, and
      address chronic infusion needs covering such ailments as diabetes, cancer and
      hypertension [1]. In all the aforementioned situations, a facility to spatially
      control porosity could offer significant advantage, such as safer controlled
      release over extended durations. Here, we describe a novel route to engineering
      in such flexibility within polymeric thin films by modifying spin-coating
      protocols to accommodate breath film patterning, that is, the spatially
      controlled condensation of pore forming droplets onto a liquid-polymer film. Upon
      film solidification, characterization via optical- and scanning probe microscopy
      revealed that local variations in porosity, as inferred from topographic
      measurements, could be effectively controlled through provision of an embossed
      vacuum holding chuck that effectively retains intimate thermal contact with the
      film substrate during forming. Parallel measurements using real time thermography
      support the hypothesis that porosity is controlled by local solvent evaporation
      rates.

PMID- 19163215
TI  - 40-MHz ultrasound imaging with chirps and annular arrays.
AB  - High-frequency ultrasound (HFU) shows promise for fine-resolution imaging.
      However, the depth of field (DOF) and penetration depth of HFU waves limit
      clinical significance. In a previous study using a 17-MHz annular array, we
      established that chirp coded excitation and synthetic focusing can improve
      penetration depth and DOF simultaneously. In this study, we evaluated the same
      approach using two five-element annular arrays with focal lengths of 12 mm, total
      apertures of 6 mm. The annular arrays had center frequencies of approximately 35
      MHz and were excited by a 4-micros chirp signal spanning the frequency range 15
      65 MHz. Results demonstrated that DOF could be increased by a factor of about 3,
      SNR could be increased by more than 10 dB, and penetration depth into an
      attenuating phantom could be increased by 1.8 mm. The chirp imaging method was
      then evaluated on low-contrast phantoms and mouse embryos.

PMID- 19163216
TI  - Focused ultrasound thermal therapy system with ultrasound image guidance and
      temperature measurement feedback.
AB  - In this study, we developed a focused ultrasound (FUS) thermal therapy system
      with ultrasound image guidance and thermocouple temperature measurement feedback.
      Hydraulic position devices and computer-controlled servo motors were used to move
      the FUS transducer to the desired location with the measurement of actual
      movement by linear scale. The entire system integrated automatic position
      devices, FUS transducer, power amplifier, ultrasound image system, and
      thermocouple temperature measurement into a graphical user interface. For the
      treatment procedure, a thermocouple was implanted into a targeted treatment
      region in a tissue-mimicking phantom under ultrasound image guidance, and then
      the acoustic interference pattern formed by image ultrasound beam and low-power
      FUS beam was employed as image guidance to move the FUS transducer to have its
      focal zone coincident with the thermocouple tip. The thermocouple temperature
      rise was used to determine the sonication duration for a suitable thermal lesion
      as a high power was turned on and ultrasound image was used to capture the
      thermal lesion formation. For a multiple lesion formation, the FUS transducer was
      moved under the acoustic interference guidance to a new location and then it
      sonicated with the same power level and duration. This system was evaluated and
      the results showed that it could perform two-dimensional motion control to do a
      two-dimensional thermal therapy with a small localization error 0.5 mm. Through
      the user interface, the FUS transducer could be moved to heat the target region
      with the guidance of ultrasound image and acoustic interference pattern. The
      preliminary phantom experimental results demonstrated that the system could
      achieve the desired treatment plan satisfactorily.

PMID- 19163217
TI  - Ultrasound beam propagation using the hybrid angular spectrum method.
AB  - We introduce a fast and accurate numerical method for simulating the propagation
      of an ultrasound beam inside inhomogeneous tissue for mapping beam absorption,
      refraction and diffraction in the body. The technique, called the hybrid angular
      spectrum method, is an extension of the angular spectrum method to inhomogeneous
      tissue. Inhomogeneous tissue is modeled using voxels, each with its own speed of
      sound, density and absorption coefficient. The proposed technique produces very
      fast simulations, with total calculation times of about one minute for a
      201x201x101 model.

PMID- 19163219
TI  - A rapid three-dimensional high intensity focused ultrasound beam plotting.
AB  - The goal of this study was to develop a rapid three-dimensional High Intensity
      Focused Ultrasound (HIFU) beam plotting system for visualizing the acoustic
      energy distribution, achieved using a three-dimensional positioning system and
      data acquisition hardware. Beam plots of a 1.1MHz HIFU transducer were performed
      to evaluate the capability of the proposed system. A three-dimensional beam
      plotting was completed in only about 30 minutes and covered a predetermined
      volume of 5mm x 20mm x 5mm with a spatial resolution of 0.2mm x 0.001mm x 0.2mm.
      The FWHM (Full Width at Half Maximum) dimensions of the ultrasound field on axial
      and lateral directions were measured at 12.51mm and 1.4mm respectively. The
      proposed system can not only perform 2-dimensional beam plots but also can aid in
      the visualization of a three-dimensional ultrasound beam pattern volume within a
      relatively short scanning time.

PMID- 19163218
TI  - A novel 100 watt high intensity focused ultrasound driving system.
AB  - Ultrasound B-Mode imaging systems are often used to image tissues to which High
      Intensity Focused Ultrasound (HIFU) is being applied. Since HIFU operates at
      frequencies in the same range as a B-mode imager, the two technologies interfere
      when they are simultaneously applied to the patient. This causes the imaging
      window to 'whiteout' and obscure the target region, thus defeating the purpose of
      using the ultrasonic imager in the first place. The system in this paper controls
      the interference window by pulsing the HIFU at a frame rate synchronized to the
      ultrasonic imager. The frame rate is either approximated by using an on-board
      oscillator, or it is captured from stray electromagnetic waves received from the
      ultrasound transducer. The system is capable of delivering 100 W of peak
      electrical output power to a HIFU transducer. It is controlled by a custom
      software application, and synchronizes with B-Mode imaging systems with frame
      rates from 10-100 Hz. An on-board Direct Digital Synthesizer generates HIFU RF
      from 1-5 MHz. The complete system provides precision positioning of the
      interference window in a small and portable desktop package.

PMID- 19163220
TI  - FFT-based computation of the bioheat transfer equation for the HCC ultrasound
      surgery therapy modeling.
AB  - This paper describes a modeling method of the tissue temperature evolution over
      time in hyperthermia. More precisely, this approach is used to simulate the
      hepatocellular carcinoma curative treatment by a percutaneous high intensity
      ultrasound surgery. The tissue temperature evolution over time is classically
      described by Pennes' bioheat transfer equation which is generally solved by a
      finite difference method. In this paper we will present a method where the
      bioheat transfer equation can be algebraically solved after a Fourier
      transformation over the space coordinates. The implementation and boundary
      conditions of this method will be shown and compared with the finite difference
      method.

PMID- 19163221
TI  - Dual apodization with cross-correlation in the presence of phase aberration and
      noise.
AB  - We have recently presented a new method to suppress side lobes and clutter in
      ultrasound imaging called dual apodization with cross-correlation or DAX. This
      method uses two apodization functions in receive mode which yield point spread
      functions with very similar main lobes but different side lobes and clutter.
      These similarities and differences are quantified by using normalized cross
      correlation of the radio frequency (RF) data in the axial direction. These cross
      correlation coefficients serve as a pixel-by-pixel weighting or filter to pass
      main lobe dominated signals and suppress clutter dominated signals. In this
      paper, we evaluate the robustness of DAX in the presence of phase aberration and
      noise. Aberrating layers of pig skin, fat, and muscle were used experimentally to
      mimic different level of aberrators. Experimental results are also presented
      using DAX in the presence of noise. With system signal-to-noise ratio (SNR) of at
      least 15 dB, we have a contrast-to-noise ratio (CNR) improvement of over 100 %
      compared to standard beamforming. This work shows that DAX is able to reliably
      improve contrast-to-noise ratio in the presence of phase aberration and noise.

PMID- 19163222
TI  - Spatiotemporal human facial expression recognition using fisher independent
      component analysis and Hidden Markov Model.
AB  - Facial expression recognition is an essential research area in the field of Human
      Computer Interface. In this work, we present a spatiotemporal approach of facial
      expression recognition using image sequences. The system proposed in this paper
      describes fisher independent component analysis as a feature extractor where the
      higher order moment classification method (i.e., independent component analysis)
      is augmented with fisher linear discriminant. This procedure is simply
      abbreviated as FICA and produces the shape based spatial facial expression
      features. For recognition, we have utilized Hidden Markov Model (HMM) to learn
      the obtained spatial features with the temporal dynamics in six different
      expressions. Our proposed approach for the first time deals with sequential
      images of emotion-specific facial expression data analyzed with FICA and
      recognized with HMM. Performance of our proposed system has been compared with
      four conventional approaches where principal component analysis, generic
      independent component analysis, enhanced independent component analysis, and
      augmented principal component analysis with linear discriminant analysis are
      utilized for feature extraction. Our preliminary results show that our proposed
      system yields much improved recognition rates reaching the mean recognition rate
      of 92.85%.

PMID- 19163223
TI  - The use of computer vision techniques to augment home based sensorised
      environments.
AB  - Technology within the home environment is becoming widely accepted as a means to
      facilitate independent living. Nevertheless, practical issues of detecting
      different tasks between multiple persons within the same environment along with
      managing instances of uncertainty associated with recorded sensor data are two
      key challenges yet to be fully solved. This work presents details of how computer
      vision techniques can be used as both alternative and complementary means in the
      assessment of behaviour in home based sensorised environments. Within our work we
      assessed the ability of vision processing techniques in conjunction with sensor
      based data to deal with instances of multiple occupancy. Our Results indicate
      that the inclusion of the video data improved the overall process of task
      identification by detecting and recognizing multiple people in the environment
      using color based tracking algorithm.

PMID- 19163224
TI  - Fall detection using multiple cameras.
AB  - Today, different ways are suggested to help elderly people in case of emergency.
      Our aim here is to propose a novel method, without any wearable device, to detect
      falls on the floor with a multiple cameras system. This proposal uses image
      analysis to localise people and reconstruct their 3D shape and position. The
      particularity of this contribution is the use of cameras sharing a large common
      field of view. Experimental results obtained with 14 different fall scenarios and
      14 normal daily activities showed a 100% fall detection efficiency.

PMID- 19163225
TI  - Towards fish-eye camera based in-home activity assessment.
AB  - Indoors localization, activity classification, and behavioral modeling are
      increasingly important for surveillance applications including independent living
      and remote health monitoring. In this paper, we study the suitability of fish-eye
      cameras (high-resolution CCD sensors with very-wide-angle lenses) for the purpose
      of monitoring people in indoors environments. The results indicate that these
      sensors are very useful for automatic activity monitoring and people tracking. We
      identify practical and mathematical problems related to information extraction
      from these video sequences and identify future directions to solve these issues.

PMID- 19163226
TI  - Anisotropic median-diffusion for filtering noisy electrocardiogram signals.
AB  - Low Noise Electrocardiogram (ECG) has been widely used for heart disease
      diagnosis. The anisotropic median-diffusion is the filter obtained by
      intercalating a median filtering in each diffusion step. We propose to use
      anisotropic median-diffusion to filter noisy ECG signals. We describe how to
      estimate appropriate parameters of the proposed filter. We validate our method
      using ECG signals from the MIT-BIH databases (many of them with premature
      ventricular contraction) and compare our method with other filtering methods.
      Experiments show that the proposed technique can effectively remove the noise
      without changing the instants and amplitudes of events, as well as preserving the
      morphologies of ECG signals in sections of the QRS complex.

PMID- 19163227
TI  - EEG and HRV markers of sleepiness and loss of control during car driving.
AB  - Heart Rate Variability (HRV) reflects the balance between sympathetic and
      parasympathetic activity. Slower HRV rhythms (LF) indicate increased sympathetic
      and/or lower vagal activity, wakefulness characteristics, while faster HRV
      rhythms (HF) indicate lower sympathetic and/or increased parasympathetic and
      vagal activity, sleepy characteristics. In this work we demonstrate that power
      spectral analysis of drivers' heart rate can report driving errors caused by
      sleepiness. Furthermore, variation of Fractal Dimension (FD) can aid significant
      information for the assessment of the driving situation. ECG and EEG data were
      collected from sleep-deprived subjects exposed to real field driving conditions.
      A lower ratio of low frequency to high frequency components (LF/HF), and lower LF
      values were reported on the occurrence of driving errors.

PMID- 19163228
TI  - Differences in evoked EEG by transcranial magnetic stimulation at various
      stimulus points on the head.
AB  - The combination of transcranial magnetic stimulation (TMS) and
      electroencephalogram (EEG) is an effective tool for investigating the cortical
      reactivity and the functional connectivity in the brain. In our previous study,
      we reported a method of removing stimulus artifact during TMS with Sample-and
      Hold circuit and EEG activity evoked by TMS could be measured successfully. In
      addition to this method, independent component analysis (ICA) was also applied to
      recorded EEG data in order to remove the stimulus artifact from for off-line
      analysis. By using these methods, short latency ( 15 ms) EEG responses to TMS
      could be obtained. In this paper, we focused on the propagation of EEG activity
      elicited by TMS. We observed both the EEG topography and the distribution of the
      current density over the whole head by changing the stimulus site. When motor
      cortex was stimulated, the propagation of EEG activity to contralateral
      hemisphere could be clearly observed. However, when posterior parietal cortex was
      stimulated, no or less propagation of EEG responses could be recognized. These
      results suggest that the responses evoked by TMS over motor cortex propagate to
      contralateral hemisphere along the axon through the corpus callosum.

PMID- 19163229
TI  - Comparison of maximum cross-correlation coefficient between blood pressure and
      heart rate with traditional index associated with baroreflex sensitivity.
AB  - In general, it is difficult to compare biological reactions to some kind of
      stimulation among subjects on the basis of a single physiological parameter such
      as heart rate variability because there is a large individual variability in its
      values. A solution to this problem is to utilize the correlation between
      physiological parameters. In previous works, the maximum cross-correlation
      coefficient between heart rate and blood pressure variabilities changed when
      subjects were strongly affected by visual stimulation. In the present work, this
      index was compared with a traditional one associated with the arterial baroreflex
      gain to investigate the mechanism of the change in the index. Resting heart rate
      and continuous blood pressure of twenty-eight healthy adults were measured for
      five minutes and analyzed. The results showed that these two indices changed
      similarly to each other while there was little correlation in the mean value
      between them. Furthermore, the lag time from blood pressure variability to heart
      rate variability was inversely correlated with the traditional index.

PMID- 19163230
TI  - Automated respiratory phase and onset detection using only chest sound signal.
AB  - The problem of non-invasive detection of respiratory phases and onsets without
      making direct airflow measurement is addressed here. Currently available
      techniques require the use of multichannel recorded sounds of both chest and
      trachea. In this paper, we propose a method which detects both respiratory phases
      and onsets using only chest sound data. Prior signal information in both time and
      frequency from the chest sound is exploited to isolate the lung component of the
      sound and the quasi-periodicity of its short-term energy is used to develop a
      configuration of nonlinear filters and bandpass filters to estimate the
      respiratory phase onsets. Performance results for the proposed method are
      reported for the case of low and medium flow rates. The average onset localizing
      accuracy of the proposed method is shown to be comparable to that obtained with
      data from more than one recording channel.

PMID- 19163231
TI  - Lung sound analysis for wheeze episode detection.
AB  - Listening and interpreting lung sounds by a stethoscope had been an important
      component of screening and diagnosing lung diseases. However this practice has
      always been vulnerable to poor audibility, inter-observer variations (between
      different physicians) and poor reproducibility. Thus computerized analysis of
      lung sounds for objective diagnosis of lung diseases is seen as a probable aid.
      In this paper we aim at automatic analysis of lung sounds for wheeze episode
      detection and quantification. The proposed algorithm integrates and analyses the
      set of parameters based on ATS (American Thoracic Society) definition of wheezes.
      It is very robust, computationally simple and yielded sensitivity of 84% and
      specificity of 86%.

PMID- 19163232
TI  - A fast discrete S-transform for biomedical signal processing.
AB  - Determining the frequency content of a signal is a basic operation in signal and
      image processing. The S-transform provides both the true frequency and globally
      referenced phase measurements characteristic of the Fourier transform and also
      generates local spectra, as does the wavelet transform. Due to this combination,
      the S-transform has been successfully demonstrated in a variety of biomedical
      signal and image processing tasks. However, the computational demands of the S
      transform have limited its application in medicine to this point in time. This
      abstract introduces the fast S-transform, a more efficient discrete
      implementation of the classic S-transform with dramatically reduced computational
      requirements.

PMID- 19163233
TI  - Feature extraction of speech signals in emotion identification.
AB  - In this work, the acoustic and spectral characteristics and the automatic
      recognition of human emotional states through speech analysis have been studied.
      Acoustic features have been evaluated and features from time-frequency
      representation are proposed. The method is based in the representation of speech
      signal through energy distributions (Gabor transform and WVD) and discrete
      coefficients (DWT and linear prediction analysis). Recognition accuracy of 94.6%
      for emotion detection are obtained from SES database of emotional speech in
      spanish language.

PMID- 19163234
TI  - Algorithm for automatic beat detection of cardiovascular pressure signals.
AB  - Pressure beat detection is an integral part of most analysis techniques for
      arterial blood pressure (ABP), intracranial pressure (ICP), and pulse oximetry
      (SpO(2)) signals. Beat detection has been used to estimate heart rate in the ABP
      signal, to classify ICP morphologies, and to estimate blood pressure using pulse
      oximeter waveforms. This paper describes an algorithm that was developed to
      detect pressure peak beats in ABP, ICP, and SpO(2) signals. When compared to the
      expert annotation of several signals consisting of over 42,500 pressure beats,
      the algorithm detected pressure peaks with an average sensitivity of 99.6% +/-
      0.27 and an average positive predictivity of 98.6% +/- 1.1.

PMID- 19163235
TI  - Gender differences in muscle fatigue of the biceps brachii and influences of
      female menstrual cycle in electromyography variables.
AB  - Several studies report gender differences in response to fatigue. Most results
      suggest that females have higher muscle endurance than males. Possible
      explanations lie on differences in muscle mass, substrate utilization, muscle
      morphology and neuromuscular activation. One relevant aspect not always
      considered is the hormonal fluctuations during the female menstrual cycle. The
      present work observed eighteen healthy and untrained adults (eight males, 26.9 +/
      4.0 yr and ten females, 24.0 +/- 2.8 yr) performing fatiguing isometric
      contractions to evaluate both the influence of menstrual cycle and gender
      differences in fatigability. Surface electromyographic signals were recorded from
      the biceps brachii using a linear electrode array of eight electrodes during 90
      seconds at 40% of maximal voluntary contraction. Root mean square (RMS), mean
      frequency (MNF) the conduction velocity (CV) values were estimated using windows
      of 0.5 seconds. Female subjects showed overall lower fatigability, demonstrated
      by the lower mean CV decrease (1.494) compared to males (1.787). However, in
      periods of high decreases in hormones concentrations in females (the end of both
      the follicular and luteal phases), higher CV decreases were observed (1.921 and
      2.183). These results indicate the need of considering the effects of hormonal
      fluctuations in females when observing gender effects on muscle fatigue.

PMID- 19163236
TI  - Detection of sleep disordered breathing by automated ECG analysis.
AB  - Sleep related breathing disorders are a highly prevalent disease associated with
      increased risk of cardiovascular complications like chronic arterial
      hypertension, myocardial infarction or stroke. Gold standard diagnostics
      (polysomnography) are complex and expensive; the need for simplified diagnostics
      is therefore obvious. As the ECG can be easily conducted during the night, the
      detection of sleep related breathing disorders by ECG analysis provides an easy
      and cheap approach. Using a combination of well known biosignals processing
      algorithms, we trained the algorithm on 35 pre-scored overnight recordings. We
      then applied the algorithm on 35 control recordings, achieving a diagnostic
      accuracy of 77%. We believe that with further improvements in ECG analysis this
      algorithm can be used for screening diagnostics of obstructive sleep apnea.

PMID- 19163237
TI  - Connectivity estimation of three parametric methods on simulated
      electroencephalogram signals.
AB  - The global framework of this paper is the connectivity estimation in multichannel
      electroencephalogram (EEG) recordings, modeled as multidimensional autoregressive
      (AR) processes. The coherence, directed transfer function and partial directed
      coherence functions are evaluated on two simulated EEG signals for their later
      application on real EEG recordings. The results were evaluated computing the
      relative error and a second proposed performance criterion (eta) based on the
      entropy of the estimated connectivity matrix.

PMID- 19163238
TI  - An application of both principal dynamic modes (PDM) and statistics for
      rehabilitation estimation related to the patients after ischemic brain stroke.
AB  - Ischemic Brain Stroke is considered to be one of the most significant reason
      causing mortality of patients. During first 60 days after brain stroke some
      critical symptoms are localized. Eventual registration of physiological
      parameters or biomedical signals e.g. heart rate variability within that time
      results in extremely difficult interpretation, most likely at the certain border
      of commonly understand sense. Therefore proper rehabilitation of such patients
      associated with well estimated results is very important as significantly
      decreases their mortality and leaves them in the highest possible well being. Due
      to rather bad quality of registered signals the need of more sophisticated
      processing method is necessary. The paper presents application of PDM for
      decomposition of HRV signals spectrum and separate estimation of behavior of both
      sympathetic and parasympathetic nervous activity. Simple ANOVA test applied for
      properly prepared data proved the anticipated results concerning significant
      difference of certain parameters e.g. sympatho-vagal balance estimated within
      mentioned 60 days period.

PMID- 19163239
TI  - Cardiovascular response to acute stress in freely moving rats: time-frequency
      analysis.
AB  - Spectral analysis of cardiovascular series is an important tool for assessing the
      features of the autonomic control of the cardiovascular system. In this
      experiment Wistar rats ecquiped with intraarterial catheter for blood pressure
      (BP) recording were exposed to stress induced by blowing air. The problem of non
      stationary data was overcomed applying the Smoothed Pseudo Wigner Villle (SPWV)
      time-frequency distribution. Spectral analysis was done before stress, during
      stress, immediately after stress and later in recovery. The spectral indices were
      calculated for both systolic blood pressure (SBP) and pulse interval (PI) series.
      The time evolution of spectral indices showed perturbed sympathovagal balance.

PMID- 19163240
TI  - Semi-blind identification of movement-related magnetoencephalogram components
      using a classification approach.
AB  - Many biomedical signal processing applications involving the analysis of multi
      channel electrophysiological recordings, such as the magnetoencephalogram (MEG)
      and electroencephalogram (EEG), increasingly employ blind source separation (BSS)
      techniques to estimate signal components reflecting artifacts and
      neurophysiological activity. While much research focuses on developing methods
      for automatic removal of artefact sources, comparatively little effort has been
      spent on trying to identify neurophysiological sources of interest, which is
      especially challenging in the absence of prior knowledge about their spatial or
      time-freqency characteristics. This work presents a method for identifying source
      signals exhibiting systematic and reliable time-frequency differences over
      clearly defined epochs associated with different 'system-states'. The proposed
      method uses annotated data and a classification approach to identify those
      sources which individually reflect significant differences between epochs
      (classes). Applied to segments of 275-channel MEG data from a visuo-motor task in
      which left, right or no finger movements occurred, the method selects only a
      small number of sources whose scalp topographies are consistent with primary
      sensorimotor cortical areas.

PMID- 19163241
TI  - Performance prediction using EEG and trial-invariant characteristic signals.
AB  - One of the most important parts of all applications trying to discriminate
      between a person's different mental tasks using their recorded EEG data is the
      process of feature construction. A common practice for this is to exploit an
      apriori knowledge about the nature of the mental processes of interest and their
      impact on the EEG signals. However, the use of features constructed in this way
      is restricted to applications concerning the corresponding mental processes. We
      present here a novel method for EEG data classification which is very general as
      it makes no assumptions about the nature of the EEG signals. It is based on the
      construction of a characteristic signal for each class which remains as invariant
      as possible over the trials belonging to that class. We use the proposed method
      in combination with a novel method for channel selection in an oddball experiment
      to predict a person's quick or late response.

PMID- 19163242
TI  - Neural time-series prediction preprocessing meets common spatial patterns in a
      brain-computer interface.
AB  - This paper shows for the first time how a popular and successful filtering
      approach, known as the common spatial patterns (CSP) approach, compares to the
      neural time series prediction preprocessing (NTSPP) approach when applied in a 2
      class EEG-based brain-computer interface (BCI), either using 2 or 60 EEG
      channels. Additionally, a novel NTSPP-CSP combination is developed to produce a 2
      channel BCI system which significantly outperforms either approach operating
      independently and has the potential to outperform a 60 channel BCI involving the
      CSP approach with no NTSPP. The advantages of reducing the number of EEG channels
      being a reduction in the time used to mount electrodes and reducing the
      obtrusiveness of the electrode montage for the user. It is also shown that NTSPP
      can improve the potential of employing existing BCI methods with no subject
      specific parameter tuning. Non subject-specific spectral filters are also
      employed with both approaches and tested with four different classifiers.

PMID- 19163243
TI  - Adaptive filtering of ballistocardiogram artifact from EEG signals using the
      dilated discrete Hermite transform.
AB  - Electroencephalogram (EEG) signals, when recorded within the strong magnetic
      field of an MRI scanner are subject to various artifacts, of which the
      ballistocardiogram (BCG) is one of the prominent ones affecting the quality of
      the EEG. The BCG artifact varies slightly in shape and amplitude for every
      cardiac cycle making it difficult to identify and remove. This paper proposes a
      novel method for the identification and elimination of this artifact using the
      shape basis functions of the new dilated discrete Hermite transform. In this
      study, EEG data within and outside the scanner was recorded. On removal of the
      BCG artifact for the EEG data recorded within the scanner, a significant
      reduction in amplitude at the frequencies associated with the BCG artifact was
      observed. In order to quantitatively assess the efficacy of this method, BCG
      artifact templates were added to segments of EEG signals recorded outside the
      scanner. These signals, when filtered using the proposed method, had no
      significant difference (p0.05) from the original signals, indicating that the
      technique satisfactorily eliminates the BCG artifact and does not introduce any
      distortions in the original signal. The method is computationally efficient for
      real-time implementation.

PMID- 19163244
TI  - Comparison of filtering and classification techniques of electroencephalography
      for brain-computer interface.
AB  - In this paper several methods are investigated for feature extraction and
      classification of mu features from electroencephalographic (EEG) readings of
      subjects engaged in motor tasks. EEG features are extracted by autoregressive
      (AR) filtering, mu-matched filtering, and wavelet decomposition (WD) methods, and
      the resulting features are classified by a linear classifier whose weights are
      set by an expert using a-priori knowledge, as well as support vector machines
      (SVM) using various kernels. The classification accuracies are compared to each
      other. SVMs are shown to offer a potential improvement over the simple linear
      classifier, and wavelets and mu-matched filtering are shown to offer potential
      improvement over AR filtering.

PMID- 19163245
TI  - A cluster analysis of neuronal activity in the dorsal premotor cortical area for
      neuroprosthetic control.
AB  - With the use of the neuronal data acquisition technology, millisecond-level multi
      electrode data from several regions of the premotor area were obtained from two
      rhesus monkeys trained to perform arm-reach tasks with visual cues in virtual
      reality. In each trial, animals were required to select and perform one of the
      four possible arm reaching movements to the target on the top-left or top-right
      of the virtual reality space. They were also required to decide whether they
      would move their arms straight to the target or curve them in order to avoid the
      obstacle that was presented. After the acquired neuronal signals were processed,
      unsupervised Hierarchical clustering and K-means clustering were performed to
      uncover the similarity and difference in the average firing rate of spike train
      data between neurons and phases for each experiment condition. The clustering
      results indicate the similarity of neuronal data in the movement planning and
      actual movement phases, and the difference of such data from the data in
      information processing phases. Furthermore, the clustering results show that when
      the target location is on the right, the move planning started earlier. The
      analysis of variance (ANOVA) on the neuronal data confirms the results from the
      hierarchical clustering.

PMID- 19163246
TI  - High-throughput in vivo genetic and drug screening using femtosecond laser nano
      surgery, and microfluidics.
AB  - We demonstrate microfluidic devices and imaging technologies for high-speed
      immobilization, cellular resolution imaging, and femtosecond laser micro-surgery
      of awake small-animals (C. elegans) for high-throughput in vivo genetic and drug
      screens on neural degeneration and regeneration.

PMID- 19163247
TI  - Applications of optical resonance to biological imaging and label-free protein
      microarrays.
AB  - We present biological imaging and sensing methods based on optical resonance and
      interference. In fluorescence microscopy, our nanoscale imaging capability sheds
      light onto conformational changes of DNA, DNA-protein complexes and polymer
      coatings on a solid surface. Interference measurements on a layered substrate
      yield a label-free sensing platform for protein binding in a high-throughput
      micro-array format.

PMID- 19163248
TI  - Harmonics tracking of intracranial and arterial blood pressure waves.
AB  - Considering cardiorespiratory interaction and heart rate variability, a new
      approach is proposed to decompose intracranial pressure and arterial blood
      pressure to their different harmonics. The method is based on tracking the
      amplitudes of the harmonics by a Kalman filter based tracking algorithm. The
      algorithm takes benefit of combined frequency estimation technique which uses
      both Fast Fourier Transform and RR-interval detection. The result would be of use
      in intracranial pressure and arterial blood pressure waveform analysis as well as
      other investigations which need to estimate contribution of specific harmonic in
      above mentioned signals such as Pressure-Volume Compensatory Reserve assessment.

PMID- 19163249
TI  - Multiharmonic tracking using sigma-point Kalman filter.
AB  - Several groups have proposed the state-space approach to track time-varying
      frequencies ofmulti-harmonic quasi-periodic signals contaminated with white
      Gaussian noise. We compared the extended Kalman filter (EKF) and sigma-point
      Kalman filter (SPKF) algorithms on this problem. On average, the SPKF
      outperformed the EKF and more accurately tracked the instantaneous frequency over
      a wide range of signal-to-noise (SNR) ratios.

PMID- 19163250
TI  - Linear and nonlinear analysis of autonomic regulation in depressed patients.
AB  - To investigate the effect of depression and medication on the autonomic nervous
      system (ANS) we compared 25 patients suffering from depression with 72 matched
      control subjects (CON). From every patient three times ECG and non-invasive blood
      pressure were recorded in: acute non-mediated state (T1), medicated state (T2)
      and clinical recovered state (T3). Cardiac autonomic regulation was evaluated by
      linear and nonlinear analysis methods. The results show that non-medicated
      depressed patients differ significantly from CON (p0.05). In the medicated state
      considerably high significant differences between depressed patient and CON were
      found (p0.0001). After an 18 months follow-up a normalization of autonomic
      parameters was achieved in depressed patients. These results show that depression
      influences autonomic parameters significantly and that medical treated clinical
      recovered patients approximate to healthy controls in autonomic regulation.

PMID- 19163251
TI  - Quantifying the similarity of multiple point processes with application to early
      diagnosis of Alzheimer's disease from EEG.
AB  - A novel approach is proposed to quantify the similarity (or 'synchrony') of
      multiple multi-dimensional point processes. It is based on a generative
      stochastic model that describes how two or more point processes are related to
      each other. As an application, the problem of diagnosing Alzheimer's disease (AD)
      from multi-channel EEG recordings is considered. The proposed method seems to be
      more sensitive to AD induced perturbations in EEG synchrony than classical
      similarity measures.

PMID- 19163252
TI  - Use of piecewise stationary segmentation as a pre-treatment for synchronization
      measures.
AB  - The analysis of the synchronization between biological signals can be helpful for
      the characterization of biological functions. Biological signals are however
      often strongly non stationary. This is in contradiction to the assumption of
      commonly used synchronization measures which assume that the signal is
      stationary. We propose to use a piecewise stationary pre-segmentation (PSP) of
      the signals of interest, before the computation of synchronization measures. We
      show on synthetic as well as real biological signals (EEG and uterine EMG) that
      the proposed piecewise stationary pre-segmentation approach increases the
      accuracy of the measures by making a good tradeoff between the stationary
      assumption and length of the analyzed segments, when compared to the classical
      windowing method.

PMID- 19163253
TI  - Automatic detection and classification of sleep stages by multichannel EEG signal
      modeling.
AB  - In this paper a novel method for automatic detection and classification of sleep
      stages using a multichannel electroencephalography (EEG) is presented.
      Understanding the sleep mechanism is vital for diagnosis and treatment of sleep
      disorders. The EEG is one of the most important tools of studying and diagnosing
      sleep disorders. EEG signals waveforms activity interpretation is performed by
      visual analysis (a very difficult procedure). This research aim is to ease the
      difficulties involved in the existing manual process of EEG interpretation by
      proposing an automatic sleep stage detection and classification system. The
      suggested method based on Multichannel Auto Regressive (MAR) model. The
      multichannel analysis approach incorporates the cross correlation information
      existing between different EEG signals. In the training phase, we used the vector
      quantization (VQ) algorithm, Linde-Buzo-Gray (LBG) and sleep stage definition, by
      estimation of probability mass functions (pmf) per every sleep stage using
      Generalized Log Likelihood Ratio (GLLR) distortion. The classification phase was
      performed using Kullback-Leibler (KL) divergence. The results of this research
      are promising with classification accuracy rate of 93.2%. The results encourage
      continuation of this research in the sleep field and in other biomedical signals
      applications.

PMID- 19163254
TI  - The effect of artifact correction on spectral estimates of heart rate
      variability.
AB  - Spectral analysis of fetal heart rate variability might offer additional
      information that can be used for assessing the fetal condition more reliably.
      Clinical recordings of fetal heart rate are usually contaminated by artifacts.
      These artifacts can be detected and corrected or removed, but this can affect the
      spectral estimates obtained from the heart rate data. To determine what level of
      artifact correction is still acceptable for reliable calculation of spectral
      heart rate variability parameters, artifact correction is simulated on neonatal
      and fetal data that did originally not contain artifacts. 2000 data segments with
      various levels of artifact correction are analyzed spectrally, and calculated
      spectral estimates are compared to the values obtained from the original,
      artifact free data. In the very low ( 0.04 Hz) and low (0.04 - 0.15 Hz) frequency
      range, powers can be calculated reliably when up to 25% of the data are missing
      due to artifact correction. Powers in the high frequency range (0.15 - 0.4 Hz for
      adults, 0.4 - 1.5 Hz for newborns) cannot be calculated reliably when data are
      missing due to artifact correction. This is a major limitation for application in
      clinical practice, which might be solved by calculating power in the high
      frequency range at a shorter time scale than power in the low frequency range.
      Short segments of heart rate data that are free of artifacts can then be used to
      calculate powers in the high frequency range reliably, while segments that
      contain artifacts are excluded.

PMID- 19163255
TI  - FPGA-core defibrillator using wavelet-fuzzy ECG arrhythmia classification.
AB  - An electrocardiogram (ECG) feature extraction and classification system has been
      developed and evaluated using Quartus II 7.1 belong to Altera Ltd. In wavelet
      domain QRS complexes were detected and each complex was used to locate the peaks
      of the individual waves. Then, fuzzy classifier block used these features to
      classify ECG beats. Three types of arrhythmias and abnormalities were detected
      using the procedure. The completed algorithm was embedded into Field Programmable
      Gate Array (FPGA). The completed prototype was tested through software-generated
      signals, in which test scenarios covering several kinds of ECG signals on MIT-BIH
      Database. For the purpose of feeding signals into the FPGA, a software was
      designed to read signal files and import them to the LPT port of computer that
      was connected to FPGA. From the results, it was achieved that the proposed
      prototype could do real time monitoring of ECG signal for arrhythmia detection.
      We also implemented algorithm in a sequential structure device like AVR
      microcontroller with 16 MHZ clock for the same purpose. External clock of FPGA is
      50 MHZ and by utilizing of Phase Lock Loop (PLL) component inside device, it was
      possible to increase the clock up to 1.2 GHZ in internal blocks. Final results
      compare speed and cost of resource usage in both devices. It shows that in cost
      of more resource usage, FPGA provides higher speed of computation; because FPGA
      makes the algorithm able to compute most parts in parallel manner.

PMID- 19163256
TI  - A wavelet denoising approach for signal action isolation in the ear canal.
AB  - The goal of this work was to develop and implement a new filtering strategy to
      denoise acoustic signals in the ear canal resulting from voluntary movement of
      the tongue (as a method of generating control input), as well as from other
      active actions, (speech, eating, drinking, smoking), and passive actions
      (swallowing, adjusting the jaw, physiological activity). The strategy is based on
      a denoising wavelet shrinkage approach that separates rhythmic bursting activity
      and white noise representing sustained tonic activity. While past work has
      addressed the discrimination of voluntary TMEP signals from one-another, no work
      has addressed acoustic artefact rejection within the ear. The results described
      here, combined with our past work in isolating critical components of tongue
      movement ear pressure (TMEP) signals, provide a basis for discriminating
      voluntary and involuntary actions of the tongue by monitoring pressure in the
      ear. At this time, the system has worked in real-time for assistive device
      control.

PMID- 19163257
TI  - Quantification method using the Morlet wavelet for magnetic resonance
      spectroscopic signals with macromolecular contamination.
AB  - We study the Morlet wavelet transform on characterizing Magnetic Resonance
      Spectroscopic (MRS) signals acquired at short echo-time. These signals contain
      contributions from metabolites, water and a baseline which mainly originates from
      large molecules, known as macromolecules, and lipids. The baseline signal decays
      faster than the metabolite ones. Therefore, by making use of the time-scale
      representation of the wavelet, the two signals can be distinguished without any
      additional pre-processing. This is confirmed by the experimental results which
      show that the Morlet wavelet can correctly quantify the metabolite contributions
      even when a baseline is embedded in the MRS signals.

PMID- 19163258
TI  - Optimized shift-invariant wavelet packet feature extraction for
      electroencephalographic evoked responses.
AB  - Local discriminant bases (LDB) have a major disadvantage in their representation
      which is sensitive to signal translations. The discriminant features will be not
      consistent when the same but shifted signal is applied. Thus, to overcome this
      problem, an approximate shift-invariant features extraction based on local
      discriminant bases is introduced. This technique is based on approximate shift
      invariant wavelet packed decomposition which integrate a cost function for
      decimation decision in each sub-band expansion. This technique gives a consistent
      best tree selection both in top-down and bottom-up search method. It also
      provides a consistent wavelet shape in a shape-adapted wavelet method to
      determine the best wavelet library for a particular signal. This method has an
      advantage especially in electroencephalographic (EEG) measurement in which there
      is an inter-individual shift in time for the signals. An application of this
      method is provided by the discrimination between signals with transcranial
      magnetic stimulation (TMS) and acoustic-somatosensory stimulation (ASS).

PMID- 19163259
TI  - Frequency interpretation of tidal peak in intracranial pressure wave.
AB  - A new approach to locate different components of ICP signal for each cardiac
      induced ICP beat is presented. In this method an initial timing map is used to
      define the appropriate part of the ICP wave which should be searched for the
      specific component. In parallel a recently proposed method was used to decompose
      the ICP wave to its different frequency harmonics. This algorithm, which is based
      on tracking the amplitude of the harmonic components using Kalman filtering,
      brings both heart rate variability and cardiorespiratory interaction into account
      and provides good time and frequency resolution. Comparing the results of two
      methods for seventeen ICP records, each one hour long, it has been observed that
      the fundamental cardiac component has the most significant contribution in the
      construction of the tidal peak in ICP and therefore tracking of this harmonic
      could be informative of the tidal peak evolution over the time.

PMID- 19163260
TI  - Microangiography system for investigation of metabolic syndrome in rat model
      using synchrotron radiation.
AB  - Metabolic syndrome refers to a clustering of cardiovascular disease risk factors.
      We investigated the characteristics of vascular endothelial function in coronary
      arteries of rats using a microangiography technique. For this study, we developed
      a microangiography system using a real-time imaging system and a third generation
      synchrotron radiation source at SPring-8. An X-ray direct-conversion type
      detector with 6-mum spatial resolution was used for real-time biomedical imaging.
      For synchrotron radiation radiography, a long source-to-object distance and a
      small source spot can produce high-resolution images. Microangiographic images
      were obtained without image blurring and were stored in a digital frame memory
      system at a maximum speed of 30 frame/s with a 1024 x 1024-pixel, 10-bit format.
      The vasorelaxation response in the coronary arteries was determined using
      coronary microangiography of ex vivo beating hearts for evaluating vascular
      endothelial dysfunction in metabolic syndrome. In imaging experiments, the small
      coronary arteries were visualized after iodine contrast agent injection into the
      coronary artery. We assessed the magnitude of coronary artery vasorelaxation
      before and after administration of drugs that modulate endothelial control of the
      coronary arteries in the rat model.

PMID- 19163261
TI  - Analysis of CR dose reduction in pediatric patients, based on computer-simulated
      noise addition.
AB  - This paper validates a technique to add statistical noise to a Computed
      Radiography (CR) in order to simulate accurately how the same image would appear
      if taken at a reduced tube current. To that, a noise addition software has been
      developed to create lower dose CR using existing pediatric radiographies based on
      the selection of lower X-ray tube current. The effect of different milliAmpere
      seconds (mAs) setting on image quality has been evaluated using the CDMAM 3.4
      phantom and the obtained results show good agreements between the simulated and
      real images in terms of noise measurement. The new CR images allow medical
      researchers to study how lower dose affects the patient diagnosis.

PMID- 19163262
TI  - Analytic noise-propagation in indirect fan-beam FBP reconstruction.
AB  - Precise knowledge of the local image noise is an essential ingredient to
      efficient application of post-processing methods such as wavelet or diffusion
      filtering to computed tomography (CT) images. The non-stationary, object
      dependent nature of noise in CT images is a direct result from the noise present
      in the projection data. Since quantum and electronics noise are the dominating
      noise sources, comparably simple models can be used for direct noise estimates in
      the individual projections. In this article, we describe the analytic propagation
      of these noise estimates through fan-beam filtered backprojection (FBP)
      reconstruction. Contrary to earlier publications in this field, we include the
      correlations within the parallel projections resulting from the rebinning, the
      convolution, and the backprojection processes. The method has been validated
      against Monte-Carlo results and good accuracy with an average relative error
      below 3.6% was achieved for arbitrary objects and over the full range of commonly
      used convolution kernels and field-of-view settings.

PMID- 19163263
TI  - Evaluation of the impact of tube current modulation on lesion detectability using
      model observers.
AB  - We use several model observers to evaluate the influence of tube current
      modulation on lesion detectability in x-ray computed tomography images
      reconstructed using the classical direct fan-beam filtered backprojection
      algorithm. Specifically, we compute observer performance for a lesion detection
      task at various locations in an elliptic water cylinder using simulated x-ray
      data. The observer performance is computed both with and without x-ray tube
      current modulation. For different tube current modulation schemes, we find that
      the Hotelling observer and the channelized Hotelling observer with Gabor channels
      yield distinctly different qualitative behavior compared to channelized Hotelling
      observers with circularly symmetric channels and to non-prewhitening observers.

PMID- 19163264
TI  - 3D weighting in cone beam image reconstruction algorithms: ray-driven vs. pixel
      driven.
AB  - A 3D weighting scheme have been proposed previously to reconstruct images at both
      helical and axial scans in stat-of-the-art volumetric CT scanners for diagnostic
      imaging. Such a 3D weighting can be implemented in the manner of either ray
      driven or pixel-drive, depending on the available computation resources. An
      experimental study is conducted in this paper to evaluate the difference between
      the ray-driven and pixel-driven implementations of the 3D weighting from the
      perspective of image quality, while their computational complexity is analyzed
      theoretically. Computer simulated data and several phantoms, such as the helical
      body phantom and humanoid chest phantom, are employed in the experimental study,
      showing that both the ray-driven and pixel-driven 3D weighting provides superior
      image quality for diagnostic imaging in clinical applications. With the
      availability of image reconstruction engine at increasing computational power, it
      is believed that the pixel-driven 3D weighting will be dominantly employed in
      state-of-the-art volumetric CT scanners over clinical applications.

PMID- 19163265
TI  - Evaluation of image noise in fan-beam x-ray computed tomography.
AB  - We investigate the problem of evaluating noise in computed tomography images that
      are reconstructed from x-ray measurements collected in fan-beam geometry. For
      reconstruction, we use the classical direct filtered backprojection method, which
      acts directly on the fan-beam projections without rebinning to the parallel-beam
      geometry. In this context, we present an accurate and efficient method to
      evaluate the image noise. This method is first validated using results from Monte
      Carlo simulations. Then, we illustrate its advantages through the implementation
      of a channelized Hotelling observer for a lesion detection task.

PMID- 19163266
TI  - Reconstruction of real tomographic data using algebraic methods.
AB  - We propose an algebraic image reconstruction method that can cope with the size
      and features of datasets produced by actual scanners, such as angular flying
      focal spot and detector offset. Image reconstruction is performed by minimizing a
      penalized least squares objective function by means of a preconditioned conjugate
      gradient (PCG) algorithm. Efficient implementation of the matrix-vector products
      that represent projection and backprojection operations is crucial to
      reconstruction speed, as such operations are performed at least once per
      iteration. For this purpose, we developed an efficient storage scheme for the
      projection matrix that allowed fast matrix-vector products. These features, along
      with an appropriate choice of the preconditioning matrix, yielded a numerically
      efficient method which produces results with better quality than those provided
      by usual filtered backprojection techniques.

PMID- 19163267
TI  - Electrical Impedance Tomography reconstruction using l1 norms for data and image
      terms.
AB  - Electrical Impedance Tomography (EIT) calculates the internal conductivity
      distribution within a body from current simulation and voltage measurements on
      the body surface. Two main technical difficulties of EIT are its low spatial
      resolution and sensitivity to measurement errors. Image reconstruction using l(1)
      norms allows addressing both difficulties, in comparison to traditional
      reconstruction using l(2) norms. A l(1) norm on the data residue term reduces the
      sensitivity to measurement errors, while the l(1) norm on the image prior reduces
      edge blurring. This paper proposes and tests a general lagged diffusivity type
      iterative method for EIT reconstructions l(1) and l(2) minimizations can be
      flexibly chosen on the data residue and/or image prior parts. Results show the
      flexibility of the algorithm and the merits of the l(1) solution.

PMID- 19163268
TI  - Improved 2-D vector field reconstruction using virtual sensors and the Radon
      transform.
AB  - This paper describes a method that allows one to recover both components of a 2-D
      vector field based on boundary information only, by solving a system of linear
      equations. The analysis is carried out in the digital domain and takes advantage
      of the redundancy in the boundary data, since these may be viewed as weighted
      sums of the local vector field's Cartesian components. Furthermore, a sampling of
      lines is used in order to combine the available measurements along continuous
      tracing lines with the digitised 2-D space where the solution is sought. A
      significant enhancement in the performance of the proposed algorithm is achieved
      by using, apart from real data, also boundary data obtained at virtual sensors.
      The potential of the proposed method is demonstrated by presenting an example of
      vector field reconstruction.

PMID- 19163269
TI  - A systematic performance analysis of the simultaneous algebraic reconstruction
      technique (SART) for limited angle tomography.
AB  - The design of limited angle tomography systems requires the optimization of
      various imaging parameters in order to achieve useful as well as reliable
      results. Algebraic reconstruction techniques, specifically the SART algorithm,
      have given excellent results in CT and are being actively considered for limited
      angle commercial applications such as tomosynthesis. In this study, we simulate a
      range of limited angle scenarios by systematically varying a number of key
      imaging parameters, and examine the performance of the SART algorithm under these
      variations. The phantoms used are basic ellipsoids in 2D, yielding analytical
      projections, and an MR-derived breast phantom in 3D.

PMID- 19163270
TI  - Penalized-likelihood reconstruction for metal artifact reduction in cone-beam CT.
AB  - CT reconstruction from metal-embedded data usually produces streak artifacts that
      reduce the quality of the reconstructed images. In this paper, we propose a new
      technique for metal artifact reduction in cone-beam CT based on statistical
      reconstruction. First, the metal objects are segmented in the reconstructed
      images and then reprojected to obtain the measurement data of the metal objects
      using cone-beam reconstruction. The original measurement data in the metal area
      are corrected through cubic interpolation. y, the corrected measurement data are
      reconstructed with the penalized likelihood using the modified convex algorithm.
      The simulation results show that the reconstructed images of the metal object
      using the proposed metal artifact reduction technique are superior to
      conventional filtered backprojection reconstruction.

PMID- 19163271
TI  - Valveless acoustic standing wave micropump for biomedical applications: a
      numerical study.
AB  - The operation principle of the valveless acoustic standing wave micropump is
      described. Time-variant flow structures through the planar diffuser-nozzle
      element of this micropump for different values of the divergence angle of the
      diffuser-nozzle element at excitation frequency of f = 20 kHz are numerically
      investigated. The variations of micropump flow rate, pressure loss coefficients
      of the nozzle and diffuser, and diffuser efficiency are shown as functions of
      theta. The higher micropump flow rate is found to be achieved at larger values of
      theta. However, increasing theta from 45. to 60. shows no significant increase in
      the net flow rate. The results also show that the maximum diffuser efficiency is
      achieved at theta = 45.

PMID- 19163272
TI  - From spikes to EEG: integrated multichannel and selective acquisition of
      neuropotentials.
AB  - Electrical signals recorded from the brain cover a wide range of amplitudes,
      frequencies, and spatial scales, from spikes and local field potentials (LFP)
      inside the brain to electrocorticograms (ECoG) and electroencepalograms (EEG)
      outside. Each of these signal modalities represent different aspects of neural
      dynamics that can be combined to infer brain state and function in a broader
      context.We present a 16-channel interface circuit fabricated in a 0.5 mum CMOS
      process for the selective acquisition and digitization of any of the modalities.
      Each channel features a fixed gain bandpass amplifier with a tunable frequency
      response which allows isolation of the signal of interest without hardware
      modification and a programmable gain/resolution analog to digital converter
      (ADC). The bandpass amplifier analog front end has an input referred noise of
      1.94 microV(rms) for a bandwidth of 8.2 kHz while drawing 12.2 microA of current
      from a 3.3 V supply. Experimental recordings with the system show spike signals
      in rat somatosensory cortex as well as alpha EEG activity in a human subject.

PMID- 19163273
TI  - On-chip chemical stimulation of neurons by local and controlled release of
      neurotransmitter.
AB  - This paper describes the fabrication and in vitro testing of a device capable of
      chemically stimulating individual neurons. Electrophoretic actuation is used to
      locally induce the release of the neurotransmitter L-glutamate in a network of
      hippocampal neurons cultured on top of the device. Cell activation by the
      neurotransmitter is visualized using calcium imaging. Single-cell stimulation is
      demonstrated close to the release site after application of a voltage of 500 mV.
      Such a device could provide a useful tool in both basic and clinical
      neuroscience. In a broader context, this device can be used to locally release
      small amounts of chemical compounds in Lab-on-Chip and drug delivery
      applications.

PMID- 19163274
TI  - Multipurpose DVD pick-up scanner for analysis of microfluidics and
      micromechanical structures.
AB  - Microfluidics has become increasingly prevalent and has founded widespread use in
      various applications such as biomedical applications (diagnostics, therapeutics,
      and cell/tissue engineering), inkjet head, and fuel cells etc. The issue of
      inspection and characterization of microfluidics has emerged as a major
      consideration in design, fabrication, and optical detection of devices. In this
      paper, we characterize the mixing flow pattern by diffusion, when two flows are
      combined in microchannel, using an optical scanner based on a DVD pick-up module,
      which is widely used in optical storage. Using Cy5.5 dye, we measure the
      fluorescent intensity that represents fluidic characteristics in Y-microchannel
      with 1 mum resolution and compare experimental results with computational fluid
      dynamics (CFD) simulation ones. Si based microstructures are measured using
      different optical reflective paths to the optical scanner with respect to the
      surface topologies. It is shown that the proposed optical scanner can be
      effectively and versatilely used to observe microfluidic characteristics and to
      measure the surface profiles of microstructures, being a cost-effective
      alternative device to conventional epifluorescent microscopes using high
      resolution CCD camera and interferometers.

PMID- 19163275
TI  - High throughput microfluidic cell array for cytotoxicity screening.
AB  - A microfluidic array with micro cell sieves was designed to fabricate multiple
      cells array for high-throughput cell cytotoxicity screening. Micro channels in
      both directions (column and row) were individually addressable by using a set of
      elastomeric monolithic array valves, enabling parallel loading of various cell
      lines in one direction and introducing of different toxins in the other
      direction. Several micro cell sieves were designed in each chamber. Cell number
      and distribution in chambers can be conveniently controlled by the adjustment of
      cell sieve number, distribution and size. Fluid transport property and cell
      loading in chamber were simulated and verified experimentally. The capability of
      the microfluidic array was demonstrated for seeding multiple mammalian cell lines
      in chambers and observing the cell viabilities after cells exposed to different
      toxins with a fluorescence microscope.

PMID- 19163276
TI  - Electrical muscle stimulation for deep stabilizing muscles in abdominal wall.
AB  - Low back pain is associated with dysfunction in recruitment of muscles in the
      lumbopelvic region. Effective rehabilitation requires preferential activation of
      deep stabilizing muscle groups. This study was carried out in order to quantify
      the response of deep stabilizing muscles (transverses abdominis) and superficial
      muscle in the abdominal wall (external oblique) to electrical muscle stimulation
      (EMS). Results demonstrate that EMS can preferentially stimulate contractions in
      the deep stabilizers and may have significant potential as a therapeutic
      intervention in this area, pending further refinements to the technology.

PMID- 19163277
TI  - Reflex bladder activation via pudendal nerve and intraurethral stimulation
      depends on stimulation pattern and location.
AB  - Pudendal nerve (PN) stimulation and intraurethral stimulation via a catheter have
      been demonstrated previously to trigger reflex bladder contractions for 20-40 Hz
      and 2 & 20 Hz continuous stimuli, respectively. However, thorough studies of the
      stimulation parameter space and optimal urethral locations are required for
      translation to clinical feasibility studies for potential neural prostheses.
      Stimulation-evoked bladder activation was evaluated in fourteen male cats via PN
      stimulation or intraurethral stimulation before and after spinal transection. In
      all testing scenarios, the use of pulse bursting led to a greater evoked bladder
      pressure than with single-pulse continuous waveforms. PN stimulation evoked
      contractions with 1 Hz and 33 Hz stimuli before spinalization in eight cats. Post
      spinalization testing in four cats only elicited excitation for 33 Hz stimuli.
      For PN stimulation, spinalization eliminated the excitability of low frequency
      stimulation. Intraurethral stimulation in the proximal and prostatic urethra (2
      Hz and 33 Hz range stimuli) and the distal urethra (33 Hz range stimuli) evoked
      contractions in six cats before spinalization. After spinalization, intraurethral
      testing in five cats only evoked contractions in the distal and prostatic urethra
      using 33 Hz range stimuli. For intraurethral stimulation, spinalization
      eliminated both proximal and low frequency responses. This research improves the
      knowledge base of several main factors involved in the development of
      neuroprostheses for bladder control - optimal stimulation paradigms and the
      understanding of lower urinary tract neurophysiology.

PMID- 19163278
TI  - Design and testing of an instrumentation system to reduce stimulus pulse
      amplitude requirements during FES.
AB  - Functional Electrical Stimulation (FES) has been used for decades to restore
      muscle function following neural trauma. Another promising use has been to
      maintain or increase muscle strength following injury. Unfortunately in the
      latter case there is considerable stimulation pain for the sensorially intact
      subject during effective levels of stimulation using surface electrodes. Recent
      research [1][2] has suggested using a constant long (up to 10 ms) low amplitude
      or ramped conditioning pulse just prior to the high amplitude stimulus pulse (100
      - 200 microsec) to reduce the excitably of sensory nerve fibers. However,
      commercial muscle stimulators cannot be easily modified to provide such complex
      pulse patterns and flexible pulse train control. We have designed and implemented
      a novel, very flexible LabVIEW based monophasic constant current muscle
      stimulator that provides pulse trains with long duration prepulses and high
      voltage stimulus pulses with selectable shapes, amplitudes, durations and
      frequencies. As well, the stimulator system includes an isolated EMG amplifier to
      record the evoked M-waves, which are used to estimate the fraction of muscle
      motor units being stimulated. We are presently testing this system, by
      stimulating the median nerve of human subjects and measuring the evoked M-waves
      for a range of stimulus pulse amplitudes, preceded by either ramped or
      rectangular low amplitude prepulses. The results indicate that, rather than
      inhibiting the activation of motor axons, as has been suggested [4], the
      prepulses at very low amplitudes excite these axons to subthreshold levels. The
      amplitudes of the stimulus pulses can then be significantly reduced while still
      achieving high levels of muscle activation.

PMID- 19163279
TI  - A time domain finite element model of extracellular neural stimulation predicts
      that non-rectangular stimulus waveforms may offer safety benefits.
AB  - Efforts to understand and model the process of extracellular neural electric
      stimulation have been driven by the desire to intelligently design neural
      prostheses in order to minimize tissue damage and to maximize the success for
      stimulating targeted neural structures. Tissue damage and electrode corrosion
      have been associated with high charge density, which is the integral of the
      current density passing through the electrode surface over the duration of the
      stimulus. Importantly, the current density distribution on the surface of
      stimulating electrodes can be extremely nonuniform, especially when high voltages
      or frequencies cause a decrease in the electrode-electrolyte impedance. Large
      current densities are found locally in regions of high curvature, such as the
      edge of a disk electrode or the tip of a conical electrode. We use a time domain
      finite element model of a platinum disk electrode and a simplified retinal
      ganglion cell to explore the potential for Gaussian and sinusoidal voltage
      controlled stimulus waveforms to reduce the nonuniformity of the current
      densities on the electrode surface while maintaining stimulation efficacy. We
      model an overpotential-dependent electrode-electrolyte interfacial impedance
      consistent with the platinum-saline interface. An excitable cell membrane is
      incorporated using the Fohlmeister-Coleman-Miller model of a retinal ganglion
      cell. Both the electrode-electrolyte interface and the cell membrane were
      incorporated into the finite element model using a thin layer approximation. All
      simulations were performed in the COMSOL Multiphysics modeling environment.
      Rectangular stimulus waveforms were compared to waveforms of Gaussian and
      sinusoidal shapes. The results suggest that Gaussian and Sinusoidal waveforms may
      significantly decrease the nonuniformity of the current density distribution
      while retaining stimulation efficacy.

PMID- 19163280
TI  - Multi-taper transfer function estimation for stimulation artifact removal from
      neural recordings.
AB  - The ability to simultaneously stimulate and record from neural tissue is
      paramount to the creation of a feedback-enabled control system. This stimulation
      creates additional electrical potential as seen by the recording system. This
      artifact can be approximated by a linear transfer function of the stimulus
      current. The computation of the transfer function is complicated by measurement
      noise and the bias and variance inherent in spectral estimation. We reduce bias
      and variance by using multi-taper techniques. We demonstrate the use of this
      transfer function as a method to remove stimulation artifact in the context of
      neural modulation with applied low-frequency (<< 100 Hz) electric fields in
      chronically instrumented animals.

PMID- 19163281
TI  - Laser stimulation of the cavernous nerves in the rat prostate, in vivo:
      optimization of wavelength, pulse energy, and pulse repetition rate.
AB  - The cavernous nerves on the prostate surface are responsible for erectile
      function. Improved diagnostic techniques are necessary for identification of the
      nerves during prostate cancer surgery and preservation of sexual function after
      surgery. Electrical mapping of the nerves has been used as an intra-operative
      tool during prostate surgery, but it has proven inconsistent and unreliable. Non
      contact optical stimulation of the cavernous nerves in the rat prostate has
      recently been demonstrated as a potential alternative to electrical nerve
      stimulation. The purpose of this study is to optimize the laser parameters to
      provide the maximum intracavernosal pressure response after optical nerve
      stimulation in the rat prostate. Optimal laser nerve stimulation parameters
      provided comparable response to electrical nerve stimulation. Optical nerve
      stimulation may represent a potential intra-operative diagnostic technique for
      use in laparoscopic and robotic nerve-sparing prostate cancer surgery.

PMID- 19163282
TI  - Characterizing nonlinear heartbeat dynamics within a point process framework.
AB  - Heartbeat intervals are known to have nonlinear and non-stationary dynamics. In
      this paper, we propose a nonlinear Volterra-Wiener expansion modeling of human
      heartbeat dynamics within a point process framework. Inclusion of second-order
      nonlinearity allows us to estimate dynamic bispectrum. The proposed probabilistic
      model was examined with two recorded heartbeat interval data sets. Preliminary
      results show that our model is beneficial to characterize the inherent
      nonlinearity of the heartbeat dynamics.

PMID- 19163283
TI  - A robust control design for heart rate tracking during exercise.
AB  - In this study, a control design is proposed for the tracking control of heart
      rate response during treadmill exercise. The controller tracks an exerciser's
      heart rate to a given heart rate profile, that may represent a prescribed
      exercise protocol, by varying the speed of the treadmill. A guaranteed cost
      control approach is adopted in the control design so that the controller
      guarantees a certain level of performance. The effectiveness of the proposed
      control design is demonstrated via a simulation study. The controller will be
      useful in the design of exercise protocols for individuals.

PMID- 19163284
TI  - Real-time monitoring of spontaneous resonance in heart rate variability.
AB  - The resonant characteristic of heart rate variability is usually generated using
      biofeedback and the external pacing of breathing, which is typically around 6
      breaths/min (0.1 Hz), although the exact frequency varies between individuals. It
      was hypothesized that the actual resonant characteristic of heart rate actually
      depends on the current psychophysiological state of the subject; therefore, the
      real-team evaluation of this form of resonance is important for a variety of
      biofeedback applications. This paper presents an analysis of the spontaneous
      resonance of heart rate variability generated during singing and non-paced slow
      breathing after breathing exercises. Two methods for automatic analysis and
      characterization of heart rate variability resonance in real-time have been
      presented. The first method uses FFT-based spectral analysis, while the second
      method calculates the period and amplitude of the RR interval variation during
      each resonant cycle. The proposed methods were tested on a 45-min record from a
      chanting session and compared with manually annotated and measured periods.

PMID- 19163285
TI  - Time-frequency analysis of cardiac and respiratory parameters for the prediction
      of ventilator weaning.
AB  - Mechanical ventilators are used to provide life support in patients with
      respiratory failure. Assessing autonomic control during the ventilator weaning
      provides information about physiopathological imbalances. Autonomic parameters
      can be derived and used to predict success in discontinuing from the mechanical
      support. Time-frequency analysis is used to derive cardiac and respiratory
      parameters, as well as their evolution in time, during ventilator weaning in 130
      patients. Statistically significant differences have been observed in autonomic
      parameters between patients who are considered ready for spontaneous breathing
      and patients who are not. A classification based on respiratory frequency, heart
      rate and heart rate variability spectral components has been proposed and has
      been able to correctly classify more than 80% of the cases.

PMID- 19163286
TI  - Detecting the temporal extent of the impulse response function from intra-partum
      cardiotocography for normal and hypoxic fetuses.
AB  - Recording of maternal uterine pressure (UP) and fetal heart rate (FHR) during
      labour and delivery is a procedure referred to as cardiotocography (CTG). We
      model this as an input-output system using a nonparametric approach to estimate
      its dynamics in terms of an impulse response function (IRF). In this paper, we
      incorporate IRF delay and memory detection into our identification methods to
      estimate the temporal extent of the IRF as well as its dynamics. Our models
      showed that pathological cases had stronger, later and more predictable
      responses.

PMID- 19163287
TI  - A comparison of fetal and neonatal heart rate variability at similar post
      menstrual ages.
AB  - Substantial differences of heart rate variability (HRV) were found between
      fetuses and prematurely born neonates in the high-frequency band of the power
      spectrum. The range of post-menstrual ages of the fetuses and neonates were
      closely matched in this study. Growth of HRV was observed in low-frequency and
      high-frequency bands, reflecting maturation of the autonomic nervous system. The
      higher level of fetal HRV in the high-frequency band persisted even after
      accounting for age-related changes. Multiscale entropy was also higher in fetuses
      than in prematurely born neonates. These results suggest that the autonomic
      balance is poorer among neonates born prematurely than in fetuses of identical
      post-menstrual age.

PMID- 19163288
TI  - The equivalent magnetizing method applied to the design of gradient coils for
      MRI.
AB  - This paper presents a new method for the design of gradient coils for Magnetic
      Resonance Imaging systems. The method is based on the equivalence between a
      magnetized volume surrounded by a conducting surface and its equivalent
      representation in surface current/charge density. We demonstrate that the curl of
      the vertical magnetization induces a surface current density whose stream line
      defines the coil current pattern. This method can be applied for coils wounds on
      arbitrary surface shapes. A single layer unshielded transverse gradient coil is
      designed and compared, with the designs obtained using two conventional methods.
      Through the presented example we demonstrate that the generated unconventional
      current patterns obtained using the magnetizing current method produces a
      superior gradient coil performance than coils designed by applying conventional
      methods.

PMID- 19163289
TI  - Radiation effects in interventional radiology using biological and physical
      dosimetry methods: a case-control study.
AB  - Interventional radiologists and staff members are frequently exposed to
      protracted and fractionated low doses of ionizing radiation, which extend during
      all their professional activities. These exposures can derive, due to the
      irradiation of skin tissues and peripheral blood, in deterministic effects
      (radiodermitis, aged skin, hands depilation) or stochastic ones (skin and non
      solid cancers incidence). Epidemiological studies of population exposed to
      ionizing radiation provide information of radio-induced effects. The radiation
      risk or radiological detriment has been estimated from a group of six exposed
      interventionist radiologists of the Hospital La Fe (Valencia, Spain). Dosimetry
      has been periodically registered from TLDs and wrist dosimeters (physical
      methods) and estimated through translocations in lymphocytes of peripheral blood
      (biological methods), by extrapolating the yield of translocations to their
      respective dose-effect curves. The probability of non-melanoma skin cancer and
      leukaemia (acute myelogenous, acute lymphocytic and chronic myelogenous
      leukaemia) incidence has been estimated through the software RADRISK. This
      software is based on a transport model from epidemiological studies of population
      exposed to external low-LET ionizing radiation [1]. Other non-solid carcinomas
      have not been considered due to their low statistical power, such as myeloid and
      non-Hodgkin lymphomas. The discrepancies observed between the physically recorded
      doses and biological estimated doses could indicate that exposed workers did not
      always wear their dosimeters or these dosimeters were not always exposed to the
      radiation field.

PMID- 19163290
TI  - Comparison and evaluation of leakage flux on various types of dental magnetic
      attachment.
AB  - A dental magnetic attachment is a device to retain dental prostheses such as
      overdentures by magnetic attraction. As compared with mechanical attachments, the
      dental magnetic attachment has superior characteristics such as easy insertion,
      good esthetics and less lateral pressure to its abutment tooth. As a result, it
      has come to be used widely. There are various types of dental magnetic
      attachments. There are a cup type and a sandwich type in Japan, and several types
      of dental magnetic attachments in other countries. They are used for a long term
      in the mouth, it is necessary to clarify those leakage magnetic fields.
      Therefore, in this paper, we evaluate the leakage magnetic fields leaking out of
      sandwich type and open magnetic circuit type of dental magnetic attachment.

PMID- 19163291
TI  - Anatomically realistic reference models of pregnant women for gestation ages of
      13, 18, and 26 weeks.
AB  - The safety of a human body exposed to radio-frequency (RF) electromagnetic fields
      (EMFs) has become important today. In recent times, conducting numerical
      dosimetry on the mother and the fetus during pregnancy has become a particularly
      important issue. This paper outlines the development of pregnant woman models
      that were adjusted to the reference values of physiological characteristics of
      maternal tissues in pregnant women for gestation ages of 13, 18, and 26 weeks The
      models are composed of voxels of 2 x 2 x 2 mm(3), and there are 56 tissue types.
      The basic specific absorption rate (SAR) characteristics in the pregnant woman
      models for whole-body exposure to RF electromagnetic fields that were calculated
      using the finite-difference time-domain (FDTD) method are described here.

PMID- 19163292
TI  - E-field errors associated with RF dosimeters for RF human exposure assessment in
      urban environments.
AB  - In this paper, the potential errors which could be associated with body-worn RF
      dosimeters have been analyzed in a multipath environment. A statistical analysis
      of the azimuth power distribution on average in an urban environment has been
      done by using the two-dimensional ray-tracing technique. The surface electric
      field on a human body when it impinges with different angles of arrival has been
      characterized based on the finite-difference time-domain method. Despite the
      differences among all the multipath scenarios presented, in the place where the
      dosimeter would be located, the variations in the electric field level at 900 MHz
      are similar but at least 5 dB lower than the E-field level when the human is not
      present.

PMID- 19163293
TI  - Research and development of a portable device to quantify muscle tone in patients
      with Parkinsons disease.
AB  - Parkinson's disease (PD) is a progressive, degenerative condition that is
      characterised by tremor, bradykinesia, cogwheel rigidity and postural
      instability. Currently, only subjective tests are employed and we aim to develop
      a portable device to quantify muscle tone in patients with movement disorders, in
      particular, Parkinson's disease. A servo-motor robotic arm was developed to
      rhythmically flex and extend the subjects arm and their response was measured
      using continuous electromyography (EMG) sampled at 4kHz. Surface electrodes were
      attached over the biceps of the more severely affected arm and a reference
      electrode attached to the back of the contra-lateral hand. EMG data was
      normalized using the rest mean EMG level and then segmented into epochs according
      to the position data. EMG recorded from normal subjects remained flat throughout
      the trial with only very small fluctuations in amplitude about the mean. In
      contrast, biceps activity in parkinsonian patients tended to increase with
      flexion and as expected there were large variations in amplitude about the
      baseline activity. A fast fourier transform was also performed and spectra
      obtained from a typical Parkinsonian patient showed two peaks at approximately 6
      Hz and 8 Hz, consistent with previously published data. In conclusion, the
      results clearly differentiate between normal and parkinsonian cases and to some
      extent severity. Quantification of disease severity might be possible given a
      broader range and greater number of patients.

PMID- 19163294
TI  - Preliminary investigation into the use of Autonomous Fall Detectors.
AB  - A study was realized in France to meet the requirements of an autonomous fall
      sensor worn on the body. It consisted of a written questionnaire of which 149
      were returned completed, which reveals that users are favorable to the use of a
      portable fall detector, worn like a watch, all through their daily activities,
      with a special wish for an audio feed back of the correct activity and, moreover,
      are ready to pay for the service on a monthly rate basis.

PMID- 19163295
TI  - Fall-detection through vertical velocity thresholding using a tri-axial
      accelerometer characterized using an optical motion-capture system.
AB  - Falls in the elderly population are a major problem for today's society. The
      immediate automatic detection of such events would help reduce the associated
      consequences of falls. This paper describes the development of an accurate,
      accelerometer-based fall detection system to distinguish between Activities of
      Daily Living (ADL) and falls. It has previously been shown that falls can be
      distinguished from normal ADL through vertical velocity thresholding using an
      optical motion capture system. In this study however accurate vertical velocity
      profiles of the trunk were generated by simple signal processing of the signals
      from a tri-axial accelerometer (TA). By recording simulated falls onto crash mats
      and ADL performed by 5 young healthy subjects, using both a single chest mounted
      TA and using an optical motion capture system, the accuracy of the vertical
      velocity profiles was assessed. Data analysis was performed using MATLAB to
      determine the peak velocities recorded and RMS error during four different fall
      and six ADL types. Results show high correlations and low percentage errors
      between the vertical velocity profiles generated by the TA to those recorded
      using the optical motion capture system. In addition, through thresholding of the
      vertical velocity profiles generated using the TA at -1.3m/s, falls can be
      distinguished from normal ADL with 100% sensitivity and specificity.

PMID- 19163296
TI  - The design and development of a long-term fall detection system incorporated into
      a custom vest for the elderly.
AB  - A fall detection system and algorithm, incorporated into a custom designed
      garment has been developed. The developed fall detection system uses a tri-axial
      accelerometer, microcontroller, battery and Bluetooth module. This sensor is
      attached to a custom designed vest, designed to be worn by the elderly person
      under clothing. The fall detection algorithm was developed and incorporates both
      impact and posture detection capability. The vest and fall algorithm was tested
      on young healthy subjects performing normal activities of daily living (ADL) and
      falls onto crash mats, while wearing the best and sensor. Results show that falls
      can de distinguished from normal activities with a sensitivity >90% and a
      specificity of >99%, from a total data set of 264 falls and 165 normal ADL. By
      incorporating the fall-detection sensor into a custom designed garment it is
      anticipated that greater compliance when wearing a fall-detection system can be
      achieved and will help reduce the incidence of the long-lie, when falls occur in
      the elderly population. However further long-term testing using elderly subjects
      is required to validate the systems performance.

PMID- 19163297
TI  - A wearable triaxial accelerometry system for longitudinal assessment of falls
      risk.
AB  - Falls-related injuries in the elderly population are a major cause of morbidity
      and represent one of the most significant contributors to hospitalizations and
      rising health care expense in developed countries. Many laboratory-based studies
      have described falls detection systems using wearable accelerometry. However,
      only a limited number of reports have tried to address the difficult issues of
      falls detection and falls prevention in unsupervised or free-living environments.
      We describe a waist-mounted triaxial accelerometry (Triax) system with a remote
      data collection capability to provide unsupervised monitoring of the elderly. The
      basis of the monitoring is a self-administered directed-routine (DR) comprising
      three separate tests measured by way of the Triax. We present an initial
      evaluation of the DR results in 36 patients to detect early changes in functional
      ability and facilitate falls risk stratification. Extracted features considered
      alone show a correlation with falls risk of approximately rho=0.5. Estimation of
      falls risk using a linear least squares model provides a root-mean-squared error
      of 0.69 (rho=0.58, p<0.0002).

PMID- 19163298
TI  - Testing of a long-term fall detection system incorporated into a custom vest for
      the elderly.
AB  - A fall detection system and algorithm, incorporated into a custom designed
      garment has been developed. The developed fall detection system uses a tri-axial
      accelerometer to detect impacts and monitor posture. This sensor is attached to a
      custom designed vest, designed to be worn by the elderly person under clothing.
      The fall detection algorithm was developed and incorporates both impact and
      posture detection capability. The vest and fall algorithm was tested by two teams
      of 5 elderly subjects who wore the sensor system in turn for 2 week each and were
      monitored for 8 hours a day. The system previously achieved sensitivity of >90%
      and a specificity of >99%, using young healthy subjects performing falls and
      normal activities of daily living (ADL). In this study, over 833 hours of
      monitoring was performed over the course of the four weeks from the elderly
      subjects, during normal daily activity. In this time no actual falls were
      recorded, however the system registered a total of the 42 fall-alerts however
      only 9 were received at the care taker site. A fall detection system incorporated
      into a custom designed garment has been developed which will help reduce the
      incidence of the long-lie, when falls occur in the elderly population. However
      further development is required to reduce the number of false-positives and
      improve the transmission of messages.

PMID- 19163299
TI  - Predicting respiratory instability in the ICU.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) contribute
      to the morbidity and mortality of intensive care patients worldwide, and have
      large associated human and financial costs. We identified a reference data set of
      624 mechanically-ventilated patients in the MIMIC-II intensive care database with
      and without low PaO(2)/FiO(2) ratios (termed respiratory instability), and
      developed prediction algorithms for distinguishing these patients prior to the
      critical event. In the end, we had four rule sets using mean airway pressure,
      plateau pressure, total respiratory rate and oxygen saturation (SpO(2)), where
      the specificity/sensitivity rates were either 80%/60% or 90%/50%.

PMID- 19163300
TI  - Dynamic biosignal management and transmission during telemedicine incidents
      handled by Mobile Units over diverse network types.
AB  - Early and specialized pre-hospital patient treatment improves outcome in terms of
      mortality and morbidity, in emergency cases. This paper focuses on the design and
      implementation of a telemedicine system that supports diverse types of endpoints
      including moving transports (MT) (ambulances, ships, planes, etc.), handheld
      devices and fixed units, using diverse communication networks. Target of the
      above telemedicine system is the pre-hospital patient treatment. While vital sign
      transmission is prior to other services provided by the telemedicine system
      (videoconference, remote management, voice calls etc.), a predefined algorithm
      controls provision and quality of the other services. A distributed database
      system controlled by a central server, aims to manage patient attributes, exams
      and incidents handled by different Telemedicine Coordination Centers (TCC).

PMID- 19163301
TI  - Diagnostic quality driven physiological data collection for personal healthcare.
AB  - We believe that each individual is unique, and that it is necessary for diagnosis
      purpose to have a distinctive combination of signals and data features that fits
      the personal health status. It is essential to develop mechanisms for reducing
      the amount of data that needs to be transferred (to mitigate the troublesome
      periodically recharging of a device) while maintaining diagnostic accuracy. Thus,
      the system should not uniformly compress the collected physiological data, but
      compress data in a personalized fashion that preserves the 'important' signal
      features for each individual such that it is enough to make the diagnosis with a
      required high confidence level. We present a diagnostic quality driven mechanism
      for remote ECG monitoring, which enables a notation of priorities encoded into
      the wave segments. The priority is specified by the diagnosis engine or medical
      experts and is dynamic and individual dependent. The system pre-processes the
      collected physiological information according to the assigned priority before
      delivering to the backend server. We demonstrate that the proposed approach
      provides accurate inference results while effectively compressing the data.

PMID- 19163302
TI  - An ontology-based approach facilitating unified querying of biosignals and
      patient records.
AB  - Electrocardiography serves as the gold standard for the noninvasive diagnosis of
      heart disease. Comparison and review between current and previous ECG recordings
      and clinical data may considerably leverage the physician's diagnostic accuracy.
      However, clinical data and ECGs are located in heterogeneous and disparate
      computer systems. On top of this, the plethora of different and mainly
      proprietary formats for ECG recording and storing, impedes the efforts towards
      aggregation of medical information. In this paper we propose an approach towards
      the seamless integration of and access to disparate and heterogeneous sources of
      medical information, through a semantically enhanced platform called SCP-ECG
      Integrated Access (SEIA). SEIA provides the means to contextualize SCP-ECG
      biosignals, by semantically structuring the clinical information they contain.
      The semantic annotation procedure is enhanced with further processing of the
      biosignal, including waveform recognition and feature extraction, for automatic
      or semiautomatic insertion of annotations where missing. Diagnosis and evaluation
      of a patient's clinical condition is facilitated through integrated temporal
      comparison of the medical information derived from successive ECGs, in terms of
      their features and annotations, along with clinical data and measurements
      originating from the Electronic Medical Record (EMR).

PMID- 19163303
TI  - Exploiting the existence of temporal heart-rate patterns for the detection of
      trauma-induced hemorrhage.
AB  - Unattended hemorrhage is a major source of mortality in trauma casualties. In
      this study, we explore a set of prehospital heart rate (HR) time-series data
      collected from 358 civilian casualties to examine whether temporal HR patterns
      can be used for automated hemorrhage identification. Continuous and reliable HR
      time series are fragmented into overlapping segments of 128 s, with a 118-s
      overlap between each two neighboring segments, which are projected into a wavelet
      coefficient space using the Haar wavelet function. A supervised nearest-neighbor
      clustering algorithm is developed to explore the existence of temporal HR
      patterns represented by the wavelet coefficients to discriminate casualties with
      and without (control) major hemorrhage. The clustering algorithm identifies 162
      HR patterns. The most frequent pattern is observed in 11 (23%) hemorrhage and 16
      (5%) control patients, which is a significant association (p<0.05, chi-square
      test). When the top 10 patterns are combined for hemorrhage detection, their
      sensitivity and specificity are 0.68 and 0.79, respectively, and when the top 20
      patterns are used sensitivity increases to 0.77 and specificity decreases to
      0.71.

PMID- 19163304
TI  - ECG quality measures in telecare monitoring.
AB  - We analyze the use of unsupervised ECG acquisition in the home environment. An
      algorithm for automatically marking ECG recordings for sections of obvious
      artifact is described. The algorithm was validated against a set of 150 records
      randomly chosen from a database of ECGs and manually annotated to identify
      sections of artifact. Using this algorithm 4751 single lead-I ECG recordings from
      24 home-dwelling patients were examined. The ECGs were collected using a remote
      home monitoring system. The participant ages (N=24) ranged from 54-92 years and
      were suffering either chronic obstructive pulmonary disease and/or congestive
      heart failure. Percentages of amplifier saturation, high frequency artifact, low
      signal power and the maximum continuous section of useable ECG are quoted. 1344
      records were found to contain no artifact, while 3506 records contained 10
      seconds or more of uninterrupted ECG (including the 1344 with no artifact). The
      results show that in the majority of cases, the capture of ECG in an unsupervised
      home environment is achievable.

PMID- 19163305
TI  - Project Alexander the Great: a study on the world proliferation of
      bioengineering/biomedical engineering education.
AB  - Bioengineering/Biomedical Engineering is considered amongst the most reputable
      fields within the global arena, and will likely be the primer for any future
      breakthroughs in Medicine and Biology. Bioengineering/biomedical engineering
      education has evolved since late 1950s and is undergoing advancement in leading
      academic institutions worldwide. This paper delineates an original study on the
      world proliferation of bioengineering/biomedical engineering education and bears
      the name 'Project Alexander the Great'. The initial step of the project was to
      survey all 10448 universities, recognized by the International Association of
      Universities, spread among the 193 member states of the United Nations within the
      six continents. The project aims at identifying, disseminating, and networking,
      through the world-wide-web, those institutions of higher learning that provide
      bioengineering/biomedical engineering education. The significance of this project
      is multifold: i) the inception of a web-based 'world-map' in
      bioengineering/biomedical engineering education for the potential international
      student desiring to pursue a career in this field; ii) the global networking of
      bioengineering/biomedical engineering academic/research programs; iii) the
      promotion of first-class bioengineering/biomedical engineering education and the
      catalysis of global proliferation of this field; iv) the erection of bridges
      among educational institutions, industry, and professional societies or
      organizations involved in Bioengineering/Biomedical Engineering; and v) the
      catalysis in the establishment of framework agreements for cooperation among the
      identified institutions offering curricula in this field. This paper presents the
      results obtained from Africa and North America. The whole project is due to be
      completed by 2009.

PMID- 19163306
TI  - Assessing learning progress and quality of teaching in large groups of students.
AB  - The classic tool of assessing learning progress are written tests and
      assignments. In large groups of students the workload often does not allow in
      depth evaluation during the course. Thus our aim was to modify the course to
      include active learning methods and student centered teaching. We changed the
      course structure only slightly and established new assessment methods like minute
      papers, short tests, mini-projects and a group project at the end of the
      semester. The focus was to monitor the learning progress during the course so
      that problematic issues could be addressed immediately. The year before the
      changes 26.76 % of the class failed the course with a grade average of 3.66 (Pass
      grade is 4.0/30 % of achievable marks). After introducing student centered
      teaching, only 14 % of students failed the course and the average grade was 3.01.
      Grades were also distributed more evenly with more students achieving better
      results. We have shown that even in large groups of students with > 100
      participants student centered and active learning is possible. Although it
      requires a great work overhead on the behalf of the teaching staff, the quality
      of teaching and the motivation of the students is increased leading to a better
      learning environment.

PMID- 19163307
TI  - Women in biomedical engineering and health informatics and its impact on gender
      representation for accepted publications at IEEE EMBC 2007.
AB  - The study of women within the professions of Engineering and Computer Science has
      consistently been found to demonstrate women as a minority within these
      professions. However none of that previous work has assessed publication
      behaviours based on gender. This paper presents research findings on gender
      distribution of authors of accepted papers for the IEEE Engineering and Medicine
      Society annual conference for 2007 (EMBC '07) held in Lyon, France. This
      information is used to present a position statement of the current state of
      gender representation for conference publication within the domain of biomedical
      engineering and health informatics. Issues in data preparation resulting from the
      lack of inclusion of gender in information gathered from accepted authors are
      presented and discussed.

PMID- 19163308
TI  - How to prepare engineers in medicine and biology?
AB  - Biomedical Engineering education has become very popular in the past two decades.
      New biomedical engineering programs have been developed to prepare students for
      this emerging field of study. Due to its highly multidisciplinary and
      interdisciplinary nature, combined with the fact that many engineering students
      have limited life sciences backgrounds, preparing graduates for an engineering
      career incorporating medicine and biology is not straight forward. The University
      of British Columbia established a graduate level biomedical engineering program
      in the fall of 2006 after an industry survey and extensive consultation process.
      The program curriculum also employs a device-based approach to the education of
      life science components including anatomy and physiology. Feedback from current
      students, industry sponsors, and practicing biomedical engineers favour this UBC
      approach. The program will continually update its curriculum and delivery style
      in response to the industry needs and student evaluation.

PMID- 19163309
TI  - Innovations in clinical trials informatics.
AB  - This paper will investigate innovations in information management for use in
      clinical trials. The application typifies a complex, adaptive, distributed and
      information-rich environment for which continuous innovation is necessary.
      Organisational innovation is highlighted as well as the technical innovations in
      workflow processes and their representation as an integrated set of web services.
      Benefits realization uncovers further innovations in the business strand of the
      work undertaken. Following the description of the development of this information
      management system, the semantic web is postulated as a possible solution to tame
      the complexity related to information management issues found within clinical
      trials support systems.

PMID- 19163310
TI  - Professional ethics in biomedical engineering practice and research.
AB  - This paper discusses some guidelines for use with the accepted fundamental canons
      of ethics for engineers. We present some rules of practice and professional
      obligations emerging from these canons. Basic recommendations for engineers
      dissenting on ethical grounds are also presented. Ethical issues relating to
      Biomedical Engineering research are illustrated. We mention some cases that could
      be used to further understanding the ethical implications of biomedical
      engineering practice.

PMID- 19163311
TI  - Open access to biomedical engineering publications.
AB  - Scientific research is disseminated within the community and to the public in
      part through journals. Most scientific journals, in turn, protect the manuscript
      through copyright and recover their costs by charging subscription fees to
      individuals and institutions. This revenue stream is used to support the
      management of the journal and, in some cases, professional activities of the
      sponsoring society such as the Institute of Electrical and Electronics Engineers
      (IEEE). For example, the IEEE Engineering in Medicine and Biology Society (EMBS)
      manages seven academic publications representing the various areas of biomedical
      engineering. New business models have been proposed to distribute journal
      articles free of charge, either immediately or after a delay, to enable a greater
      dissemination of knowledge to both the public and the scientific community.
      However, publication costs must be recovered and likely at a higher cost to the
      manuscript authors. While there is little doubt that the foundations of
      scientific publication will change, the specifics and implications of an open
      source framework must be discussed.

PMID- 19163312
TI  - Classification of low-level finger contraction from single channel surface EMG.
AB  - This paper reports a study that has investigated a new technique to identify very
      low level finger flexion by the classification of single channel surface
      electromyogram (sEMG). The technique is based on decomposing of sEMG based on the
      model of transmission of motor unit action potentials (MUAP) in body tissues.
      This technique is relevant for identifying control commands that are often based
      on low level and complex muscle contraction such as finger flexion which are
      often a convenient way for a user to control equipment or a prosthesis device.
      Use of single channel is extremely important because it does not require an
      expert to mount the electrodes and has a further advantage in reduced cost and
      computational complexity. The paper reports experiments conducted on four healthy
      volunteer subjects with four actions and tested over 50 repetition and a high
      classification accuracy.

PMID- 19163313
TI  - Classification of Temporomandibular disorder from electromyography signals via
      Directed Transfer Function.
AB  - A new approach for the detection of Temporomandibular joint disorders (TMDs) from
      the recorded electromyography (EMG) signals from the muscles around the
      temporomandibular joint (TMJ) has been presented in this paper. Multivariate
      Autoregressive (MVAR) modelling has been applied to a six-channel set of EMG
      signals from the muscles of both sides of the jaw during mouth opening and
      closing. The MVAR coefficients are then used to define the Directed Transfer
      Function (DTF), which estimates the strength of the direction of the signals flow
      between the channels. The DTF energy parameters were chosen as the features for
      EMG classification using support vector machine (SVM). The method described here
      has a potential to detect and classify the type and level of muscular disorder
      from the way the muscle signals interact with each other.

PMID- 19163314
TI  - Non-invasive distress evaluation in preterm newborn infants.
AB  - With the increased survival of very preterm infants, there is a growing concern
      for their developmental outcomes. Infant cry characteristics reflect the
      development and possibly the integrity of the central nervous system. In this
      paper, relationships between fundamental frequency (F(0)) and vocal tract
      resonance frequencies (F(1)-F(3)) are investigated for a set of preterm newborns,
      by means of a multi-purpose voice analysis tool (BioVoice), characterised by high
      resolution and tracking capabilities. Also, first results about possible distress
      occurring during cry in preterm newborn infants, as related to the decrease of
      central blood oxygenation, are presented. To this aim, a recording system
      (Newborn Recorder) has been developed, that allows synchronised, non-invasive
      monitoring of blood oxygenation and audio recordings of newborn infant's cry. The
      method has been applied to preterm newborns at the Intensive Care Unit, A.Meyer
      Children Hospital, Firenze, Italy.

PMID- 19163315
TI  - Predicting the length of stay for neonates using heart-rate Markov models.
AB  - Recently, there has been an increase in preterm newborn's survival and as a
      result longer length of stay (LOS) in neonatal intensive care units (NICU) have
      been observed. Conseqyently, there has been an increased interest in accurate
      prediction of the LOS. Most of the existing techniques are based on physiological
      parameters i.e., scores such as (SNAP-II or SNAPPE-II). In this paper we propose
      to predict the length of stay using heart-rate measurements combined with
      physiological scores. We propose to model the heart-rate using Markov chain model
      and estimate transition probabilities using maximum likelihood estimator and the
      patient population from Neonatal Intensive Care Unit at McMaster Hospital. We
      then derive the maximum likelihood estimators of LOS using physiological
      measurements and transition probabilities. Training and test data sets were used
      to verify the proposed linear and nonlinear estimators.

PMID- 19163316
TI  - Spectral analysis on the microcirculatory laser Doppler signal of the acupuncture
      effect.
AB  - We aim to analyze the frequency content of skin blood flow signals recorded on
      Hoku following acupuncture stimulation (AS). Each experiment involved recording a
      20-minute control-data sequence and two effects data recorded 0-20 and 50-70
      minutes after stopping AS, respectively. 4-level Haar-wavelet transform was
      performed on the measured LDF signals, and periodic oscillations with five
      characteristic frequency peaks were obtained within the frequency interval:
      0.0095-0.021, 0.021-0.052, 0.052-0.145, 0.145-0.6, and 0.6-1.6 Hz, respectively.
      Band proportion and DC component of the flux signal were calculated to elucidate
      the effects following AS. At Hoku, the DCflux was significantly increased, the
      band proportion of the 1st and the 2nd frequency band were significantly
      decreased, and that of the 5th band was significantly increased following AS. Our
      results facilitate a non-invasive method to evaluate sympathetic control of
      peripheral vascular activity between the acupoint and non-acupoints, which may be
      important for studying the therapeutic effects of AS.

PMID- 19163317
TI  - ECG QRS Complex detection with programmable hardware.
AB  - In recent years, algorithm based on Mathematical Morphology and wavelet transform
      has been proposed for ECG QRS Complex detection. However, its intensity of
      computation is high. This paper proposes the algorithm and hardware architecture
      for the whole system of QRS Complex detection based on Mathematical Morphology
      and Quadratic Spline wavelet transform, with implementation in Field Programmable
      Gate Array (FPGA). The system consists of Morphological filtering, Quadratic
      Spline wavelet transform and Modulus Maxima Pair Recognition modules. The
      parallel and pipelined architecture of system can operate in the maximum 35MHz
      with throughput of one sample per clock cycle. The QRS Complex detection accuracy
      for MIT/BIH arrhythmia database recordings and resource consumption are reported.
      The design is suitable for both batch processing of huge volume ECG data and real
      time applications for portable devices.

PMID- 19163318
TI  - Wavelet entropy characterization of elevated intracranial pressure.
AB  - Intracranial Hypertension (ICH) often occurs for those patients with traumatic
      brain injury (TBI), stroke, tumor, etc. Pathology of ICH is still controversial.
      In this work, we used wavelet entropy and relative wavelet entropy to study the
      difference existed between normal and hypertension states of ICP for the first
      time. The wavelet entropy revealed the similar findings as the approximation
      entropy that entropy during ICH state is smaller than that in normal state.
      Moreover, with wavelet entropy, we can see that ICH state has the more focused
      energy in the low wavelet frequency band (0-3.1 Hz) than the normal state. The
      relative wavelet entropy shows that the energy distribution in the wavelet bands
      between these two states is actually different. Based on these results, we
      suggest that ICH may be formed by the re-allocation of oscillation energy within
      brain.

PMID- 19163319
TI  - Detection and classification of raw action potential patterns in human Muscle
      Sympathetic Nerve Activity.
AB  - The Muscle Sympathetic Nerve Activity (MSNA) consists of synchronous neural
      discharges separated by periods of neural silence dominated by heavy background
      noise. During measurement with electrodes, the raw MSNA signal is amplified, band
      pass filtered, rectified and integrated. This integration process removes much
      neurophysiological information. In this paper a method for detecting a raw action
      potential (before the pre-amplifier) and filtered action potential (after the
      band-pass filter) is presented. This method is based on stationary wavelet
      transform (SWT) and a peak detection algorithm. Also, the detected action
      potentials were clustered using the k-means method and the cluster averages were
      calculated. The action potential detector and classification algorithm are
      evaluated using real MSNA recorded from three healthy subjects.

PMID- 19163320
TI  - Performance analysis of stationary and discrete wavelet transform for action
      potential detection from sympathetic nerve recordings in humans.
AB  - Accurate investigation of the sympathetic nervous system is important in the
      diagnosis and study of various autonomic and cardiovascular control and
      disorders. Sympathetic function associated with blood pressure regulation in
      humans can be evaluated by recording muscle sympathetic nerve activity (MSNA),
      which is characterised by synchronous neuronal discharges separated by periods of
      neural silence dominated by colored gaussian noise. In this paper two common
      methods for detecting filtered action potential in MSNA recordings is compared.
      These methods are based on stationary wavelet transform (SWT) and discrete
      wavelet transform (DWT). The performance analysis are evaluated using simulated
      MSNA using templates extracted from real MSNA recorded from three healthy
      subjects.

PMID- 19163321
TI  - A method for the determination and hardware validation of biosignal processing
      parameters.
AB  - This paper proposes an iterative procedure for the determination of parameters
      and working conditions of biomedical signal processing algorithms. A
      systematization of the process required to determine the parameters is proposed,
      avoiding "trial and error" tests, and considering all the specific requirements
      of a Telemedicine system, such as reliability and guaranteed signal
      reconstruction quality. An application of the method is included, also, focusing
      on ECG processing. Hardware platform Biolet(E) is designed for validation in an
      electronic implementation.

PMID- 19163322
TI  - Quantifying cardio-pulmonary correlations using the cross-wavelet transform:
      validating a correlative method.
AB  - Dynamic changes in physiologic systems have become an increasingly important
      topic in biomedical signal processing. To demonstrate a novel approach to this
      type of analysis, we recorded the cardiac and respiratory rhythms of six normal
      subjects over 5 minutes. We used cross-wavelet transforms to identify any
      correlations between these signals and then a unique approach to surrogate data
      generation in the frequency domain to confirm the statistical significance of the
      correlations that were found. The cross-wavelet transform provides a means of
      statistically quantifying weak correlations between systems that might otherwise
      not show significant interactions, while the method of surrogate data generation
      is a robust way of confirming a true physiological relationship.

PMID- 19163323
TI  - Wavelet approach to artifact noise removal from Capacitive coupled
      Electrocardiograph.
AB  - Capacitive coupled Electrocardiography (ECG) is introduced as non-invasive
      measurement technology for ubiquitous health care and appliance are spread out
      widely. Although it has many merits, however, capacitive coupled ECG is very weak
      for motion artifacts for its non-skin-contact property. There are many studies
      for artifact problems which treats all artifact signals below 0.8Hz. In our
      capacitive coupled ECG measurement system, artifacts exist not only below 0.8Hz
      but also over than 10Hz. Therefore, artifact noise removal algorithm using
      wavelet method is tested to reject artifact-wandered signal from measured
      signals. It is observed that using power calculation each decimation step,
      artifact-wandered signal is removed as low frequency artifacts as high frequency
      artifacts. Although some original ECG signal is removed with artifact signal, we
      could level the signal quality for long term measure which shows the best quality
      ECG signals as we can get.

PMID- 19163324
TI  - Compression of electromyographic signals using image compression techniques.
AB  - Despite the growing interest in the transmission and storage of electromyographic
      signals for long periods of time, few studies have addressed the compression of
      such signals. In this article we present an algorithm for compression of
      electromyographic signals based on the JPEG2000 coding system. Although the
      JPEG2000 codec was originally designed for compression of still images, we show
      that it can also be used to compress EMG signals for both isotonic and isometric
      contractions. For EMG signals acquired during isometric contractions, the
      proposed algorithm provided compression factors ranging from 75 to 90%, with an
      average PRD ranging from 3.75% to 13.7%. For isotonic EMG signals, the algorithm
      provided compression factors ranging from 75 to 90%, with an average PRD ranging
      from 3.4% to 7%. The compression results using the JPEG2000 algorithm were
      compared to those using other algorithms based on the wavelet transform.

PMID- 19163325
TI  - An improved method for 2-D ECG compression based on SPIHT algorithm.
AB  - An improved wavelet based 2-D ECG compression method is presented which employs
      set partitioning in hierarchical trees (SPIHT) algorithm and run length (RL)
      coding. The proposed 2-D approach utilizes the fact that ECG signal shows
      redundancy between adjacent beats and also adjacent samples. The results of
      several experiments show that the wavelet function biorthogonal-6.8 with five
      level of decomposition has better performance compared to others. In period
      normalization repeating each beat instead of zero padding is more efficient. The
      initializing of list of insignificant pixels (LIP) is also done in a different
      way. Results of applying the proposed algorithm on several record of MIT/BIH
      database show lower percent root mean square difference (PRD) than other 1-D and
      several 2-D methods for the same compression ratio.

PMID- 19163326
TI  - A human auditory tuning curves matched wavelet function.
AB  - This paper proposes a new quantitative approach to the problem of matching a
      wavelet function to a human auditory tuning curves. The auditory filter shapes
      were derived from the psychophysical measurements in normal-hearing listeners
      using the variant of the notched-noise method for brief signals in forward and
      simultaneous masking. These filters were used as templates for the designing a
      wavelet function that has the maximum matching to a tuning curve. The scaling
      function was calculated from the matched wavelet function and by using these
      functions, low pass and high pass filters were derived for the implementation of
      a filter bank. Therefore, new wavelet families were derived.

PMID- 19163327
TI  - Feature extraction based on time-frequency and Independent Component Analysis for
      improvement of separation ability in Atrial Fibrillation detector.
AB  - Due to redundancy of over-dimensioned information, observed often in originally
      recorded biomedical signals, feature extraction and selection has become focus of
      much researches connected with biomedical signal processing and classification.
      Mixed new feature vector combined from time-frequency signal representation
      (obtained after wavelet transform) and Independent Component Analysis (ICA)
      applied for non-stationary signals is proposed as a preliminary stage in ECG
      waveform classification for patients with Atrial Fibrillation (AF). Discrete fast
      wavelet transform coefficients parameters including energy and entropy measures
      and components extracted as a result of FastICA algorithm implementation after
      optimization gave the best classifier performance of whole AF ECG classifier
      system. System was positively verified on the set of clinically classified ECG
      signals for control and atrial fibrillation (AF) disease patients taken from
      MITBIH data base. The measures of specificity and sensitivity computed for the
      set of 20 AF and 20 patients from control group divided into learning and
      verifying subsets were used to evaluate presented pattern recognition structure.
      Different types of wavelet basic functions for feature extraction stage and
      kernels for SVM classifier structure calculation were tested to find the best
      system architecture. Obtained results showed, that the ability of generalization
      and separation for enriched feature extraction based system increased, due to
      selectively choosing only the most representative features for analyzed AF
      detection problem.

PMID- 19163328
TI  - Bone surface reconstruction using localized freehand ultrasound imaging.
AB  - We propose a bone surface reconstruction method using localized ultrasound
      imagery. A set of bone contours is first extracted from a series of freehand 2D B
      mode localized images, using an automatic segmentation method. This set is then
      used to reconstruct the bone surface with a tensor product B-splines
      approximation. Results of the partial surface reconstruction are shown for real
      bones and for a phantom physical model.

PMID- 19163329
TI  - Normalization and backscatter spectral analysis of human carotid arterial data
      acquired using a clinical linear array ultrasound imaging system.
AB  - The risk of plaque rupture in carotid atherosclerotic disease is associated more
      closely with the composition of plaque rather than the severity of stenosis. The
      constituents of plaque can be determined from ultrasonic spectral parameters
      obtained from normalized backscatter tissue data. Calibration of the data is done
      using echoes off a specular reflector which removes the system response of an
      ultrasound transducer, Terason (Teratech Corporation), from the backscatter data.
      A reference spectrum study is used to compare specular reflectors based on time
      domain (echo) and frequency domain (power spectrum, centroid and parabola test)
      analysis. Nylon and a tissue-mimicking phantom (velocity = 1560 m/s, slope of
      attenuation = 0.7 dB/cm MHz) have an intermediate acoustic impedance with respect
      to water and appear good choices as specular reflectors for clinical ultrasound
      imaging scanners compared to Plexiglas and other higher reflecting materials. A
      tissue-mimicking phantom is used to correct for attenuation in plaque,
      diffraction and saturation of electronics of the ultrasound scanner.
      Autoregressive power spectrum estimation methods are used to extract spectral
      parameters (spectral slope, y-intercept, midband fit, maximum and minimum power
      with corresponding frequencies, and integrated backscatter) from calibrated
      tissue data and linear and quadratic discriminant rules developed for
      classification of carotid arterial plaque. Regions of interest (n = 64; 64
      samples x 8 scan lines with 30 MHz sampling frequency) consisting of 48 fibrous
      fibrofatty (Class 1), 11 thrombus-necrotic core (Class 2), and 5 dense calcium
      (Class 3) areas selected for analysis show that fibrosis can be differentiated
      from necrosis and calcification. The quadratic discriminant rule identified
      necrosis with a lower misclassification rate (9.1%) than the linear discriminant
      rule (18.2%).

PMID- 19163330
TI  - Design, development and characterization of cyst phantom for ultrasound
      elastography applications.
AB  - Polyacrylamide based tissue mimicking phantom with embedded cysts is designed and
      analyzed for better understanding of cyst elastograms. Cysts filled with
      different fluids of varying density and bulk moduli are embedded in the phantom.
      Characterization is done based on parameters measured from the ultrasound B mode
      and elastogram of the cystic lesions. Such a phantom can serve as tool for better
      understanding of the elastographic appearance of cysts. Thus simple and complex
      cysts can be easily distinguished. It can also be used to teach a complex
      procedure like ultrasound guided fine needle aspiration.

PMID- 19163331
TI  - Time delay estimation of discrete samples in ultrasound echo signals.
AB  - The performances of various signal-processing applications in ultrasound medical
      imaging, including elastography, blood flow imaging, tissue velocity imaging, and
      acoustic radiation force impulse imaging, depend on their time-delay estimators.
      In this paper, we introduced a new class of time-delay estimator based on the
      tracking of individual samples using a continuous representation of the echo
      signal. Simulation results show that the sample tracking algorithms significantly
      outperformed the conventional window-based algorithms in terms of bias and jitter
      when individual estimates from the samples are averaged over the same window
      length. Simulations further showed similar performance to that of recently
      introduced spline-based continuous time-delay estimators only if all the samples
      in the window had identical delays. When the samples inside a window experienced
      different delays, sample tracking algorithms considerably outperformed the
      continuous delay estimators. In addition, the sample tracking algorithms showed
      to have much higher resolution and sensitivity when compared to all the other
      window-based techniques, including the continuous delay estimators.

PMID- 19163332
TI  - Automatic identification of lumbar level with ultrasound.
AB  - An ultrasound-based system is created to label the lumbar vertebrae for the
      purpose of percutaneous needle insertion. Many lumbar punctures have a preferable
      vertebral level for needle insertion, but the traditional method of manual
      palpation is known to be inaccurate for determining the level. Needle insertion
      for epidural anesthesia in obstetrics is preferably performed at the L3-L4
      interspace and miscalculation can lead to complications such as nerve damage and
      paralysis. Similar risks occur for other spinal needle insertions. In this paper,
      an ultrasound-based system is devised that creates panorama images of lumbar
      vertebrae with an extended field of view starting from the coccyx. The vertebrae
      are labeled with a novel image processing algorithm. Since the coccyx is
      relatively easy to locate by palpation, the labels of the vertebrae from the
      panorama can be converted to skin location on the subject. The method is
      validated against independent measurements by a sonographer.

PMID- 19163333
TI  - Ultrasound thermal change detection based on steerable filters.
AB  - Growing tendency toward utilization of Laser and RF knives has opened a new port
      for thermal control applications in which ultrasound thermal detection is
      crucial. Ultrasound velocity is dependent on the thermal properties of the
      environment. In this paper we focus on tissue temperature detection using
      multiresolution steerable filter-based motion estimation. The proposed technique
      was evaluated on simulated and real in-vivo cases during surgical occlusion and
      reopening of renal segmental artery and demonstrated promising results for
      observation of internal organ temperature changes using only digital ultrasound
      systems for diagnosis and therapy. It is proved that being oriented in space and
      time, steerable filters can achieve more accurate results. Performing thermal
      detection methods on synthetic phantoms demonstrated good correlation between
      speckle shifts and the ground truth temperature. For the simulated images average
      thermal error was 0.68 degrees Celsius with a standard deviation of 0.79.

PMID- 19163334
TI  - 3D prostate segmentation based on ellipsoid fitting, image tapering and warping.
AB  - This paper presents a 3D semi-automatic prostate segmentation method for B-mode
      trans-rectal ultrasound (TRUS) images. Segmentation is based on prior knowledge
      of the prostate transversal section shape which is assumed to be a tapered
      ellipse. The approach consists of an initial untapering and warping of the image
      to make the shape of the prostate approximately elliptical. The prostate contour
      is found in the untapered, warped images by edge detection and 2D/3D ellipsoidal
      curve fitting, performed by solving convex optimization problem. This leads to an
      average total segmentation duration of 7.42s which is more than 40 times faster
      than manual segmentation. Clinical studies carried out on 58 prostate volume
      studies show a volume sensitivity and accuracy of approximately 94% and 73%
      respectively.

PMID- 19163335
TI  - Automatic 3D segmentation of prostate in MRI combining a priori knowledge, Markov
      fields and Bayesian framework.
AB  - Accurate localization and contouring of prostate are important issues in prostate
      cancer diagnosis and/or therapies. Although several semi-automatic and automatic
      segmentation methods have been proposed, manual expert correction remains
      necessary. Our paper introduces an original method for automatic 3D segmentation
      of the prostate gland from Magnetic Resonance Imaging data. We use a statistical
      shape model as a priori knowledge, and we model gray levels distribution by
      fitting histogram modes with a Gaussian mixture. Markov fields are used to
      introduce contextual information regarding voxels neighbourhood. Final labelling
      optimization is based on Bayesian a posteriori classification, estimated with the
      Iterative Conditional Mode algorithm (ICM). We compared the accuracy of this
      method, free from any manual correction, with contours outlined by an expert
      radiologist. In 6 random cases, including prostates with cancer and benign
      prostatic hypertrophy (BPH), mean Hausdorff distance (HD) and Overlap Ratio (OR)
      were 9.94 mm and 0.83, respectively. Beyond fast computing times, this new method
      showed satisfying results, even at prostate's base and apex.

PMID- 19163337
TI  - Edge cross-section features for detection of appendiceal orifice appearance in
      colonoscopy videos.
AB  - Colonoscopy is an endoscopic technique that allows a physician to inspect the
      inside of the human colon. The appearance of the appendiceal orifice during
      colonoscopy indicates a complete traversal of the colon, which is one of
      important quality indicators of examination of the colon. In this paper, we
      propose a new algorithm that detects appendix images-images showing the
      appendiceal orifice. We introduce new features based on geometric shape,
      saturation and intensity changes along the norm direction (cross-section) of an
      edge to discriminate appendix images. Our experimental results on real
      colonoscopic images show the average sensitivity and specificity of 88.12% and
      94.25%, respectively.

PMID- 19163336
TI  - CAD of colon cancer on CT colonography cases without cathartic bowel preparation.
AB  - Computer-aided diagnosis (CAD) systems must show sufficient versatility to
      produce robust analysis on a large variety of data. In the case of colonography,
      CAD has not been designed to cope with the presence of stool, although labeling
      the stool with high contrast agents replaces the use of laxatives and reduces the
      patient discomfort. This procedure introduces additional challenges for the
      diagnosis, such as poorly tagged stool, stool sticking to colonic walls, and
      heterogeneous stool (tagged stool mixed with air or untagged stool). Our study
      proposes a robust algorithm for heterogeneous stool removal to be employed as a
      preprocessing module for CAD systems in colonic cancer detection. Colonoscopy
      data are automatically cleansed of residual stool to enhance the polyp appearance
      for improved diagnosis. The algorithm uses expectation-maximization, quadratic
      regression, level sets and minimum variance. Results show stool removal accuracy
      on polyps which are partially or fully covered by stool. The results are robust
      on stool lining and large pools of heterogeneous and weakly-tagged stool. The
      automatic detection of colon polyps using our CAD system on cathartic-free data
      improves considerably with the addition of the automatic stool removal module
      from 74% to 86% true positive (TP) rate at 6.4 false positives (FP)/case.

PMID- 19163339
TI  - Wavelet domain Bayesian method for high noise level PET image reconstruction.
AB  - In this paper, a new maximum a posterior(MAP) method for PET image reconstruction
      defined in wavelet domain is proposed. Compared to the conventional MAP methods
      with Markov Random Field (MRF) prior models, the proposed method, named WD-MAP
      method, has better performance in characterize both local and global feature of
      reconstructed image due to the wavelet transform. Wavelet packet decomposition
      strategy is applied to further improve the reconstruction quality. The
      convergence speed of WD-MAP method is accelerated by adopting conjugate
      gradient(CG) technique. Simulated experiment suggests that the proposed method
      offers competitive performance in PET image reconstruction.

PMID- 19163338
TI  - Stool detection in colonoscopy videos.
AB  - Colonoscopy is the accepted screening method for detection of colorectal cancer
      or its precursor lesions, colorectal polyps. Indeed, colonoscopy has contributed
      to a decline in the number of colorectal cancer related deaths. However, not all
      cancers or large polyps are detected at the time of colonoscopy, and methods to
      investigate why this occurs are needed. One of the main factors affecting the
      diagnostic accuracy of colonoscopy is the quality of bowel preparation. The
      quality of bowel cleansing is generally assessed by the quantity of solid or
      liquid stool in the lumen. Despite a large body of published data on methods that
      could optimize cleansing, a substantial level of inadequate cleansing occurs in
      10% to 75% of patients in randomized controlled trials. In this paper, a machine
      learning approach to the detection of stool in images of digitized colonoscopy
      video files is presented. The method involves the classification based on color
      features using a support vector machine (SVM) classifier. Our experiments show
      that the proposed stool image classification method is very accurate.

PMID- 19163340
TI  - Detection of small bowel tumors in capsule endoscopy frames using texture
      analysis based on the discrete wavelet transform.
AB  - Capsule endoscopy is an important tool to diagnose tumor lesions in the small
      bowel. The capsule endoscopic images possess vital information expressed by color
      and texture. This paper presents an approach based in the textural analysis of
      the different color channels, using the wavelet transform to select the bands
      with the most significant texture information. A new image is then synthesized
      from the selected wavelet bands, trough the inverse wavelet transform. The
      features of each image are based on second-order textural information, and they
      are used in a classification scheme using a multilayer perceptron neural network.
      The proposed methodology has been applied in real data taken from capsule
      endoscopic exams and reached 98.7% sensibility and 96.6% specificity. These
      results support the feasibility of the proposed algorithm.

PMID- 19163341
TI  - Wavelet denoising during optical coherence tomography of the prostate nerves
      using the complex wavelet transform.
AB  - Preservation of the cavernous nerves during prostate cancer surgery is critical
      in preserving sexual function after surgery. Optical coherence tomography (OCT)
      of the prostate nerves has recently been studied for potential use in nerve
      sparing prostate surgery. In this study, the discrete wavelet transform and
      complex dual-tree wavelet transform are implemented for wavelet shrinkage
      denoising in OCT images of the rat prostate. Applying the complex dual-tree
      wavelet transform provides improved results for speckle noise reduction in the
      OCT prostate image. Image quality metrics of the cavernous nerves and signal-to
      noise ratio (SNR) were improved significantly using this complex wavelet
      denoising technique.

PMID- 19163342
TI  - Semi automatic MRI prostate segmentation based on wavelet multiscale products.
AB  - Currently, prostate cancer is the third leading cause of cancer-related deaths
      among men in North America. As with many others types of cancer, early detection
      and treatment greatly increases the patient's chance of survival. MRI prostate
      segmentation allows clinical personnel to design an accurate treatment plan. A
      novel method for MRI prostate imagery segmentation is proposed in this paper.
      This method exploits the different behavior presented by signal singularities and
      noise in the wavelet domain in order to accurately detect the borders around the
      prostate. The prostate contour is then traced by using a set of spatially variant
      rules that are based on prior knowledge about the general shape of the prostate.
      The proposed method yielded promising results when applied to real data.

PMID- 19163343
TI  - A Bayesian wavelet-based multidimensional deconvolution with sub-band emphasis.
AB  - This paper proposes a new algorithm for wavelet-based multidimensional image
      deconvolution which employs subband-dependent minimization and the dual-tree
      complex wavelet transform in an iterative Bayesian framework. In addition, this
      algorithm employs a new prior instead of the popular l(1) norm, and is thus able
      to embed a learning scheme during the iteration which helps it to achieve better
      deconvolution results and faster convergence.

PMID- 19163344
TI  - Measures for the evaluation of bias field removal procedures in MRI and the
      design of wavelets for suppression of RF inhomogeneities.
AB  - RF inhomogeneities are illumination artifacts in MR images which manifest as a
      multiplicative bias field. To measure the quality of an MR image with respect to
      RF inhomogeneities, existing multi-valued criteria are in use. Here we propose a
      useful conversion of these multi-valued criteria into a single measure of quality
      which simplifies image quality evaluation and comparison. Next, to remove such a
      bias field, a novel wavelet based approach is employed, that extends a previous
      1D wavelet design methodology to a 2D setting. This method is found to perform
      well on images with strong small details. The results for brain MR images are
      subject to improvement, however our results hint to a future scenario for
      improved image quality.

PMID- 19163345
TI  - A Self Organizing Map approach to breast cancer detection.
AB  - Detection and characterization of cancer tumors in mammograms is vital in daily
      clinical practice. The problem of detecting possible cancer areas is very complex
      due, on one hand, to the diversity in shape of the ill tissue and on the other
      hand to the poorly defined border between the healthy and the cancerous zone.
      Even though it has been studied for many years, there are still remaining
      challenges and directions for future research such as developing better
      enhancement and segmentation algorithms. The performance of the Self Organizing
      Map (SOM) in detecting the cancer suspicious regions in digitized mammograms is
      revealed in this study. In order to achieve the best results we firstly apply the
      preprocessing algorithms proposed in section II of the study.

PMID- 19163346
TI  - Multistage processing procedure for 4D breast MRI segmentation.
AB  - Contrast-enhanced magnetic resonance imaging (MRI) is a novel approach to detect
      breast tumor, however, multiple 3D image sets need to be analyzed which causes
      unaffordable inspection tasks to physicians. Computer assistant detection is of
      great help to this situation and image segmentation is most important process of
      computer assistant detection. To segment the breast region from 3D MRI set, a
      multistage image processing procedure was proposed. Considering the morphological
      features of breast image, the image was divided into two parts to reduce the
      complexity of the segmentation procedure. For the anterior part of the image, the
      breast tissue was segmented from background using the region growing method.
      Meanwhile, the mean intensity of breast tissue was estimated. To segment the
      posterior part of the image, the estimated mean breast intensity was used to
      initialize an approximate boundary between breast and chest. The estimated
      intensity distribution of breast tissue was used to set the propagation term of
      following level set iterations. Based on this initialization, threshold-based 3D
      level set algorithm was used to seek the precise boundary between chest and
      breast. The level set algorithm achieves novel performance for the 3D
      segmentation of chest boundary. Based on the segmentation of one set of 3D image,
      the segmentation result was used as the initial boundary of following image sets
      to achieve automatic 4D segmentation. This multistage procedure greatly
      accelerates the convergence of the level set algorithm and reduces the chance of
      running into local minimum. Clinical data demonstrated that this processing
      procedure was effective for automatic segmentation of 4D breast MRI.

PMID- 19163347
TI  - Edge intensity normalization as a bias field correction during balloon snake
      segmentation of breast MRI.
AB  - Segmentation of fat suppressed dynamic contrast enhanced MRI (DCE-MRI) image data
      can pose significant problems because of the inherently poor signal-to-noise
      ratio (SNR) and intensity variations due to the bias field. Segmentation methods
      such as balloon snakes, while able to operate in a poor SNR environment, are
      sensitive to variations in edge intensity, which are regularly encountered within
      DCE-MRI due to the bias field. In order to overcome the effects of the bias
      field, an intensity normalization based on the strength of the strongest edge,
      i.e. the skin-air-boundary, is proposed and evaluated. This normalization allows
      balloon segmentations to be run three times faster while maintaining, or even
      improving accuracy.

PMID- 19163348
TI  - Breast cancer diagnosis using level-set statistics and support vector machines.
AB  - Breast cancer diagnosis based on microscopic biopsy images and machine learning
      has demonstrated great promise in the past two decades. Various feature selection
      (or extraction) and classification algorithms have been attempted with success.
      However, some feature selection processes are complex and the number of features
      used can be quite large. We propose a new feature selection method based on level
      set statistics. This procedure is simple and, when used with support vector
      machines (SVM), only a small number of features is needed to achieve satisfactory
      accuracy that is comparable to those using more sophisticated features.
      Therefore, the classification can be completed in much shorter time. We use multi
      class support vector machines as the classification tool. Numerical results are
      reported to support the viability of this new procedure.

PMID- 19163349
TI  - A multi-classifier and decision fusion framework for robust classification of
      mammographic masses.
AB  - Most end-to-end Computer Aided Diagnosis (CAD) systems follow a three step
      approach - (1) Image enhancement and segmentation, (2) Feature extraction, and,
      (3) Classification. While the state of the art in image enhancement and
      segmentation can now very accurately identify regions of interest for feature
      extraction, they typically result in very high dimensional feature spaces. This
      adversely affects the performance of classification systems because a large
      feature space dimensionality necessitates a large training database to accurately
      model the statistics of class features (e.g. benign versus malignant classes). In
      this work, we present a robust multi-classifier decision fusion framework that
      employs a divide-and-conquer approach for alleviating the affects of high
      dimensionality of feature vectors. The feature space is partitioned into multiple
      smaller sized spaces, and a bank of classifiers (a multi-classifier system) is
      employed to perform classification in each of the partition. Finally, a decision
      fusion system merges decisions from each classifier in the bank into a single
      decision. The system is applied to the problem of classifying digital
      mammographic masses as either benign or malignant.

PMID- 19163350
TI  - Automatic breast cancer grading of histopathological images.
AB  - Breast cancer grading of histopathological images is the standard clinical
      practice for the diagnosis and prognosis of breast cancer development. In a large
      hospital, a pathologist typically handles 100 grading cases per day, each
      consisting of about 2000 image frames. It is, therefore, a very tedious and time
      consuming task. This paper proposes a method for automatic computer grading to
      assist pathologists by providing second opinions and reducing their workload. It
      combines the three criteria in the Nottingham scoring system using a multi
      resolution approach. To our best knowledge, there is no existing work that
      provide complete grading according to the Nottingham criteria.

PMID- 19163351
TI  - Objective evaluation of methods for border detection in dermoscopy images.
AB  - Dermoscopy is one of the major imaging modalities used in the diagnosis of
      melanoma and other pigmented skin lesions. Due to the difficulty and subjectivity
      of human interpretation, dermoscopy image analysis has become an important
      research area. Border detection is often the first step in the automated analysis
      of dermoscopy images. Although numerous methods have been developed for the
      detection of lesion borders, very few studies were comprehensive in the
      evaluation of their results. In this paper, we evaluate five recent border
      detection methods on a set of 90 dermoscopy images using three sets of
      dermatologist-drawn borders as the ground-truth. In contrast to previous work, we
      utilize an objective measure, the Normalized Probabilistic Rand Index, which
      takes into account the variations in the ground-truth images. The results
      demonstrate that the differences between four of the evaluated border detection
      methods are in fact smaller than those predicted by commonly used measures.

PMID- 19163352
TI  - Segmentation of scalp and skull in neonatal MR images using probabilistic atlas
      and level set method.
AB  - In this paper, we present a novel automatic algorithm for scalp and skull
      segmentation in T1-weighted neonatal head MR images. First, the probabilistic
      scalp and skull atlases are constructed. Second, the scalp outer surface is
      extracted based on an active mesh method. Third, maximum number of boundary
      points corresponding to the scalp inner surface is extracted using the
      constructed scalp probabilistic atlas and a set of knowledge based rules. In the
      next step, the skull inner surface and maximum number of boundary points of the
      outer surface are extracted using a priori information of the head anatomy and
      the constructed skull probabilistic atlas. Finally, the fast sweeping, tagging
      and level set methods are applied to reconstruct surfaces from the detected
      points in three-dimensional space. The results of the new segmentation algorithm
      on MRI data acquired from nine newborns (including three atlas and six test
      subjects) were compared with manual segmented data provided by an expert
      radiologist. The average similarity indices for the scalp and skull segmented
      regions were equal to 89% and 71% for the atlas and 84% and 63% for the test
      data, respectively.

PMID- 19163353
TI  - Segmentation and analysis of the glomerular basement membrane using the split and
      merge method.
AB  - Certain renal diseases are characterized by alterations in the thickness of the
      glomerular basement membrane (GBM), as visualized by images of biopsy samples
      obtained by using a transmission electron microscope (TEM). Abnormal thinning,
      thickening, or variation in thickness can occur in familial hematuria, diabetes
      mellitus, and Alport syndrome, respectively. We propose image processing methods
      for the segmentation and measurement of the GBM. The methods include the split
      and merge algorithm, morphological image processing, skeletonization, and
      statistical analysis of the width of the GBM. The proposed methods were applied
      to 34 TEM images of six patients. The mean and standard deviation of normal GBM
      were estimated to be 368 +/- 177 nm; those of thin GBMs associated with familial
      hematuria were 216 +/- 95 nm; and those of thick GBM due to diabetic nephropathy
      were 1094 +/- 361 nm. Comparative analysis of the results of image processing
      with manual measurements by an experienced renal pathologist indicated low error
      in the range of 12 +/- 9 nm.

PMID- 19163354
TI  - Object contour extraction in medical images by fast adaptive B-Snake.
AB  - Detection of edge contours to define the object class and segmenting it from the
      background(s) class is a major challenge in medical image processing. In this
      paper, we introduce a fast adaptive B-Spline Snake algorithm that overcomes the
      limitations of previous B-Snakes by avoiding computationally expensive
      optimization stages. Furthermore, we present novel strategies for adaptive knot
      insertion to fulfill the specific requirements of the medical application
      accordingly. Experimental results on pulmonary CT images and brain MR images
      demonstrated that our method is superior both in accuracy and convergence speed
      over previous B-Spline Snake algorithms. The proposed algorithm is also robust to
      missing the boundaries.

PMID- 19163355
TI  - A new method based on dynamic programming for boundary detection in ultrasound
      image sequences.
AB  - Dynamic programming has previously been used when measuring Lumen Diameter (LD)
      and Intima-Media Thickness (IMT) in single frame ultrasound carotid artery images
      [1]. An extension to multiframe detection of that procedure is proposed in this
      paper. Our new method transforms a three dimensional problem into multiple two
      dimensional problems that can again be solved by dynamic programming. First,
      several 'candidate boundaries' are detected in each image. Then, one boundary
      from each image in the sequence is selected in such a way that the sequence of
      boundaries is optimal among the considered possibilities. A model of the
      movements of the boundaries is used in the second step. Our proposed method shows
      promising performance on both synthetic and real ultrasound data.

PMID- 19163356
TI  - Segmentation of leukocytes and erythrocytes in blood smear images.
AB  - Differential blood count is a standard method in hematological laboratory
      diagnosis. In the course of developing a computer-assisted microscopy system for
      the generation of differential blood counts, the detection and segmentation of
      white and red blood cells forms an essential step and its exactness is a
      fundamental prerequisite for the effectiveness of the subsequent classification
      step. We propose a method for the exact segmentation of leukocytes and
      erythrocytes in a simultaneous and cooperative way. We combine pixel-wise
      classification with template matching to locate erythrocytes and use a level-set
      approach in order to get the exact cell contours of leukocyte nucleus and plasma
      regions as well as erythrocyte regions. An evaluation comparing the performance
      of the algorithm to the manual segmentation performed by several persons yielded
      good results.

PMID- 19163357
TI  - Towards a framework for analysis of biophotonic images of mouse models of cancer.
AB  - Biophotonic imaging can be used to characterize tumor growth in animal models.
      Estimation of the numbers and location of target cells is dependent on accurate
      segmentation of a target region from the background luminescence of the animal
      body. Existing software systems extract general regions of interest in complex
      images but can fail to detect details or faint regions of interest in the
      presence of higher luminescent activity. Limited work has been published in the
      analysis of these images. We explore the use of popular medical image
      segmentation techniques in segmentation of bioluminescence images. The ability of
      each algorithm in detecting regions of interest is tested using established
      performance measures. Based on the characteristics of bioluminescence images of
      animal tumor models, and the performance of the algorithms, we formulate a
      framework for segmentation techniques best suited for this application.

PMID- 19163358
TI  - Improved interactive medical image segmentation using Enhanced Intelligent
      Scissors (EIS).
AB  - A novel interactive approach called Enhanced Intelligent Scissors (EIS) is
      presented for segmenting regions of interest in medical images. The proposed
      interactive medical image segmentation algorithm addresses the issues associated
      with segmenting medical images and allows for fast, robust, and flexible
      segmentation without requiring accurate manual tracing. A robust complex wavelet
      phase-based representation is used as an external local cost to address issues
      associated with contrast non-uniformities and noise typically found in medical
      images. The boundary extraction problem is formulated as a Hidden Markov Model
      (HMM) and the novel approach to the second-order Viterbi algorithm with state
      pruning is used to find the optimal boundary in a robust and efficient manner
      based on the extracted external and internal local costs, thus handling much
      inexact user boundary definitions than existing methods. Experimental results
      using MR and CT images show that the proposed algorithm achieves accurate
      segmentation in medical images without the need for accurate boundary definition
      as per existing Intelligent Scissors methods. Furthermore, usability testing
      indicate that the proposed algorithm requires significantly less user interaction
      than Intelligent Scissors.

PMID- 19163359
TI  - Multislice human organ extraction based on GVF.
AB  - Segmentation techniques based on active contours algorithm are widely used in
      medical imaging. Unfortunately, they require a lot of parameters to be used and
      this can represent an issue for those physicians with not much informatics
      skills. This paper proposes a software tool which allows to segment multiple
      slice can differ organ extraction setting a small number of parameters. Moreover,
      the tool offers the functionality to perform a multiple segmentation the same
      time, so that an entire volume composed by hundreds slices can be segmented.

PMID- 19163360
TI  - A mean shift based fuzzy c-means algorithm for image segmentation.
AB  - Image segmentation is an important task in many medical applications. One family
      of segmentation algorithms is based on the idea of clustering pixels with similar
      characteristics. C-means based approaches, in particular fuzzy c-means has been
      shown to work well for clustering based segmentation, however due to the
      iterative nature are also computationally complex. In this paper we introduce a
      new mean shift based fuzzy c-means algorithm that we show to be faster than
      previous techniques while providing good segmentation performance. The proposed
      clustering method incorporates a mean field term within the standard fuzzy c
      means objective function. Since mean shift can quickly and reliably find cluster
      centres, the entire strategy is capable of optimally segmenting clusters within
      an image.

PMID- 19163361
TI  - Enhancing watershed segmentation of touching and weakly-connected features in
      biomedical images.
AB  - We report how to improve and control watershed segmentation of touching features
      in optical-microscope images of immunochemically stained cells and in three
      dimensional (3D) reconstruction of weak-connected components in transmission
      electron microscopy images from ultra-thin slices of compact chromatin clumps,
      from rat lymphocytes. Our approach includes image processing of the distance
      transform domain, and a discrete-boundary formulation of morphological operators,
      to speed up the 3D watershed segmentation. The adjustment for connectivity
      criteria, as well as other tuning parameters, come from the Nyquist sampling
      criterion, applied to spatial resolution, and are obtained from biological
      considerations, such as the average size of a normal cell. We also combined both
      enhancements in 3D and present the mathematical background as well as visual
      results.

PMID- 19163362
TI  - Semi-automatic medical image segmentation with adaptive local statistics in
      Conditional Random Fields framework.
AB  - Planning radiotherapy and surgical procedures usually require onerous manual
      segmentation of anatomical structures from medical images. In this paper we
      present a semi-automatic and accurate segmentation method to dramatically reduce
      the time and effort required of expert users. This is accomplished by giving a
      user an intuitive graphical interface to indicate samples of target and non
      target tissue by loosely drawing a few brush strokes on the image. We use these
      brush strokes to provide the statistical input for a Conditional Random Field
      (CRF) based segmentation. Since we extract purely statistical information from
      the user input, we eliminate the need of assumptions on boundary contrast
      previously used by many other methods, A new feature of our method is that the
      statistics on one image can be reused on related images without registration. To
      demonstrate this, we show that boundary statistics provided on a few 2D slices of
      volumetric medical data, can be propagated through the entire 3D stack of images
      without using the geometric correspondence between images. In addition, the image
      segmentation from the CRF can be formulated as a minimum s-t graph cut problem
      which has a solution that is both globally optimal and fast. The combination of a
      fast segmentation and minimal user input that is reusable, make this a powerful
      technique for the segmentation of medical images.

PMID- 19163363
TI  - Image segmentation of ovitraps for automatic counting of Aedes Aegypti eggs.
AB  - The Aedes Aegypti mosquito is the vector of the most difficult public health
      problems in tropical and semi-tropical world: the epidemic proliferation of
      dengue, a viral disease that can cause human beings death specially in its most
      dangerous form, dengue haemorrhagic fever. One of the most useful methods for
      mosquito detection and surveillance is the ovitraps: special traps to collect
      eggs of the mosquito. It is very important to count the number of Aedes Aegypti
      eggs present in ovitraps. This counting is usually performed in a manual, visual
      and non-automatic form. This work approaches the development of automatic methods
      to count the number of eggs in ovitraps images using image processing,
      particularly color segmentation and mathematical morphology-based non-linear
      filters.

PMID- 19163364
TI  - Real-time Raman spectroscopy for non-invasive skin cancer detection - preliminary
      results.
AB  - Raman spectroscopy is a non-invasive optical technique, which can assess
      molecular structures and conformations within biological tissue. The probability
      of Raman scattering is inherently low such that previous clinical applications of
      Raman spectroscopy have been limited by long data acquisition times. We have
      developed a rapid real-time Raman spectrometer system with measurement times of
      less than 1 second, paving the way for clinical application. In this
      presentation, we report preliminary clinical results for this real-time Raman
      system. To date 289 skin cancers and benign skin lesions have been measured.
      Using partial least squares regression and linear discriminant analysis to
      analyze the Raman spectra we found that skin cancers could be well differentiated
      from benign skin lesions (sensitivity 91% and specificity 75%) and malignant
      melanoma from benign pigmented lesions (sensitivity 97%, specificity 78%).

PMID- 19163365
TI  - Malignant melanoma detection by Bag-of-Features classification.
AB  - In this paper, we apply a Bag-of-Features approach to malignant melanoma
      detection based on epiluminescence microscopy imaging. Each skin lesion is
      represented by a histogram of codewords or clusters identified from a training
      data set. Classification results using Naive Bayes classification and Support
      Vector Machines are reported. The best performance obtained is 82.21% on a
      dataset of 100 skin lesion images. Furthermore, since in melanoma screening false
      negative errors have a much higher impact and associated cost than false positive
      ones, we use the Neyman-Pearson score in our model selection scheme.

PMID- 19163366
TI  - PASuite: a preprocessing algorithm suite for cellular and molecular image
      classification in cancer diagnosis and treatment.
AB  - We present a generalized tool to mark and preprocess cancerous regions in an
      image. Currently, tissue biopsies are analyzed and graded manually by expert
      pathologists and thus can be time consuming and challenging due to variations in
      tissue morphology, inconsistencies in preparation of tissue specimen and errors
      in the image acquisition process. Our tool is designed to automatically
      standardize the variations in different images due to changing illumination and
      experimental conditions. Segregating cancerous regions from non-cancerous areas
      is a mandatory step before extracting relevant information from cancer images
      such as the number and size of nuclei and subsequently using it for
      classification and quantitative analysis. We tested our tool for two completely
      different cancers: Head and Neck Cancer (HNC) and Renal Cell Carcinoma (RCC). The
      tool enables the user to successfully segment the cancerous areas for both types
      of cancers and our results match with the manual validation by a pathologist.

PMID- 19163367
TI  - Pulmonary tumor volume delineation in PET images using deformable models.
AB  - Lung cancer is one of the most lethal form of cancer worldwide. The tumor present
      in the lungs is not static and changes its shape and position during each
      breathing cycle. In order to segment the tumor, the physicians manually outline
      the tumor on each slice. Slice by slice manual segmentation is prone to errors
      and causes physician fatigue. A semi-automatic method to segment and track the
      tumor in all the frames of PET data is proposed in this paper. The tumor is
      segmented from each slice of the first frame using wavelet features and support
      vector machine classifier. This segmented tumor, after validated by the experts
      is used in initialization of the contour for segmentation of the tumor in
      subsequent frames by the level set method. Another important contribution of this
      paper is setting up tumor volume obtained from the first frame as the termination
      condition for the level set method. The results obtained from the proposed
      methodology are very promising and eliminates the need for manual tumor
      segmentation. Our proposed technique also maintains consistent segmentation and
      the results obtained are not dependent on the operator as is the case in manual
      segmentation.

PMID- 19163368
TI  - A new method based on both fuzzy set and possibility theories for tumor volume
      segmentation on PET images.
AB  - A new automatic method for tumor volume segmentation on PET images has been
      developed. The method introduced in this paper is based on previous works in MRA
      segmentation and involves both fuzzy set and possibility theories. Visual results
      prove the method efficiency which is confirmed by obtained Jaccard index.

PMID- 19163369
TI  - Landmarking of computed tomographic images to assist in segmentation of abdominal
      tumors caused by neuroblastoma.
AB  - Segmentation of the primary tumor mass in neuroblastoma could aid radiologists by
      facilitating reproducible and objective quantification of the tumor's tissue
      composition and size. However, due to the heterogeneous nature of the tissue
      components of the neuroblastic tumor, ranging from low-attenuation necrosis to
      high-attenuation calcification, some of which possess strong similarities with
      adjacent nontumoral tissues in computed tomographic (CT) images, segmentation of
      the tumor is a difficult problem. In this context, landmarking methods are
      proposed to assist in the segmentation of neuroblastic tumors. Methods are
      proposed to identify and segment automatically the rib structure, the vertebral
      column, the spinal canal, the diaphragm, and the pelvic girdle. The use of the
      landmarks assisted in limiting the scope of the tumor segmentation process to the
      abdomen, and resulted in the reduction of the false-positive error rates by
      26.9%, on the average, over 10 CT exams, and improved the result of segmentation
      of neuroblastic tumors.

PMID- 19163370
TI  - A deformable model-based system for 3D analysis and visualization of tumor in
      PET/CT images.
AB  - This paper presents a tumor detecting system that allows interactive 3D tumor
      visualization and tumor volume measurements. An improved level set method is
      proposed to automatically segment the tumor images slice by slice. PET images are
      used to detect the tumor while CT images make a 3D representation of the
      patient's body possible. An initial slice with a seed within the tumor is firstly
      chosen by the operator. The system then performs automatically the tumor volume
      segmentation that allows the clinician to visualize the tumor, to measure it and
      to evaluate the best medical treatment adapted to the patient.

PMID- 19163371
TI  - Epifluorescence-based quantitative microvasculature remodeling using geodesic
      level-sets and shape-based evolution.
AB  - Accurate vessel segmentation is the first step in analysis of microvascular
      networks for reliable feature extraction and quantitative characterization.
      Segmentation of epifluorescent imagery of microvasculature presents a unique set
      of challenges and opportunities compared to traditional angiogram-based vessel
      imagery. This paper presents a novel system that combines methods from
      mathematical morphology, differential geometry, and active contours to reliably
      detect and segment microvasculature under varying background fluorescence
      conditions. The system consists of three main modules: vessel enhancement, shape
      based initialization, and level-set based segmentation. Vessel enhancement deals
      with image noise and uneven background fluorescence using anisotropic diffusion
      and mathematical morphology techniques. Shape-based initialization uses features
      from the second-order derivatives of the enhanced vessel image and produces a
      coarse ridge (vessel) mask. Geodesic level-set based active contours refine the
      coarse ridge map and fix possible discontinuities or leakage of the level set
      contours that may arise from complex topology or high background fluorescence.
      The proposed system is tested on epifluorescence-based high resolution images of
      porcine dura mater microvasculature. Preliminary experiments show promising
      results.

PMID- 19163372
TI  - Segmentation of arterial vessel wall motion to sub-pixel resolution using M-mode
      ultrasound.
AB  - We describe a method for segmenting arterial vessel wall motion to sub-pixel
      resolution, using the returns from M-mode ultrasound. The technique involves
      measuring the spatial offset between all pairs of scans from their cross
      correlation, converting the spatial offsets to relative wall motion through a
      global optimization, and finally translating from relative to absolute wall
      motion by interpolation over the M-mode image. The resulting detailed wall
      distension waveform has the potential to enhance existing vascular biomarkers,
      such as strain and compliance, as well as enable new ones.

PMID- 19163373
TI  - Estimation of carotid diameter with heartbeat on longitudinal B-mode ultrasonic
      images.
AB  - Arteriosclerosis, i.e. degrading arterial elasticity, causes cerebral infarction
      and myocardial infarction. Premonition of arteriosclerosis is important because
      arteriosclerosis is never cured completely. We therefore propose a method to
      track the carotid diameter to evaluate the initial carotid elasticity accompanied
      with a person's heartbeat using the longitudinal B-mode ultrasonic images. If the
      diameter of carotid artery can be accurately estimated, it is possible to implies
      for initial inference of the presence of arteriosclerosis. In future studies, it
      has to be assessed with comparisons to anaother established method.

PMID- 19163374
TI  - Automated detection of the carotid artery wall in B-mode ultrasound images using
      active contours initialized by the Hough Transform.
AB  - Automatic segmentation of the arterial lumen from ultrasound images is an
      important and often challenging task in clinical diagnosis. We previously used
      the Hough Transform (HT) to automatically extract circles from sequences of B
      mode ultrasound images of transverse sections of the carotid artery. In this
      paper, an active-contour-based methodology is suggested, initialized by the HT
      circle, in an attempt to extend previous findings and to accurately detect the
      arterial wall boundary. The methodology is based on the generation of a gradient
      vector flow field, an approach attempting to overcome conventional active
      contours constraints. Contour estimation is then achieved by deforming the
      initial curve (circle) based on the gradient vector flow field. In ten normal
      subjects, the specificity and accuracy of the segmentation were on average higher
      than 0.98, whereas the sensitivity was higher than 0.82. The methodology was also
      applied to four subjects with atherosclerosis, in which sensitivity, specificity
      and accuracy were comparable to those of normal subjects. In conclusion, the HT
      initialized active contours methodology provides a reliable tool to detect the
      carotid artery wall in ultrasound images and can be used in clinical practice.

PMID- 19163375
TI  - Three-dimensional labeling of vulnerable regions in carotid plaques using Graph
      Cuts.
AB  - Carotid plaque morphology assessed through high resolution ultrasound is nowadays
      an important diagnostic approach in the evaluation of stroke risk. The literature
      describes several methods for the characterization of plaque echogenicity and
      texture by using overall statistics across the carotid plaques. However, this
      averaged indicators may not be enough for a correct diagnosis of plaque
      instability. Therefore, it has been suggested that a local characterization of
      plaque morphology, where the extension and location of vulnerable regions inside
      the plaques is taken into account, could lead to significant improvements in the
      assessment of stroke risk. In this paper, a new method to characterize the
      morphology of carotid plaques in three-dimensions (3D) is proposed. The local
      characterization of carotid plaques is performed by using a 3D Graph-Cuts
      (GraphC) robust labeling method. This methodology allows to binary segment the
      data by minimizing an energy function that uses spatial correlation among
      neighboring pixels/voxels in order to remove small misclassified regions. The
      method is efficient since it is able to find the global minimum of the energy
      function in a very short time interval. Results show that this labeling procedure
      is less noisier and favors clustering, being more meaningful from a clinical
      point of view than the one obtained with simple thresholding. This paper shows
      that the use of GraphC may improve the 3D morphological characterization of
      carotid plaques, namely by providing a more appropriate identification of
      unstable foci inside the plaque.

PMID- 19163376
TI  - A neural amplifier with high programmable gain and tunable bandwidth.
AB  - A neural recording amplifier having programmable gain and bandwidth is presented.
      The gain can be digitally programmed using 6 bits from 100x to 1100x in steps of
      100x. The low-frequency cutoff can be varied from less than 10Hz to above 100Hz
      to accept or reject field potentials while the high-frequency cutoff is fixed at
      9kHz. The input referred noise of this amplifier is 4.8microV(rms) and it
      consumes 50microW operating from +/-1.5V. Implemented in a 0.5microm technology,
      the amplifier occupies an area of 0.098mm(2). This amplifier has been
      successfully demonstrated in-vivo and compared to a commercial amplifier.

PMID- 19163377
TI  - Flexible polymer substrate and tungsten microelectrode array for an implantable
      neural recording system.
AB  - This paper describes the process flow and testing of a substrate for a fully
      implantable neural recording system. Tungsten microwires are hybrid-packaged on a
      micromachined flexible polymer substrate forming an intracortical microelectrode
      array for brain machine interfaces. The microelectrode array is characterized on
      the bench top and tested in vivo. The microelectrode noise floor is less than 2
      microV and acute recording results show a signal to noise ratio of 9.9-17.3 dB.
      The technique of hybrid fabrication of the electrodes on a flexible substrate
      provides a general platform for the development of an implantable neural
      recording system.

PMID- 19163378
TI  - A miniaturized glucose biosensor for in vitro and in vivo studies.
AB  - A miniaturized wireless glucose biosensor has been developed to perform in vitro
      and in vivo studies. It consists of an external control subsystem and an implant
      sensing subsystem. The implant subsystem consists of a micro-processor, which
      coordinates circuitries of radio frequency, power regulator, command demodulator,
      glucose sensing trigger and signal read-out. Except for a set of sensing
      electrodes, the micro-processor, the circuitries and a receiving coil were
      hermetically sealed with polydimethylsiloxane. The electrode set is a substrate
      of silicon oxide coated with platinum, which includes a working electrode and a
      reference electrode. Glucose oxidase was immobilized on the surface of the
      working electrode. The implant subsystem bi-directionally communicates with the
      external subsystem via radio frequency technologies. The external subsystem
      wirelessly supplies electricity to power the implant, issues commands to the
      implant to perform tasks, receives the glucose responses detected by the
      electrode, and relays the response signals to a computer through a RS-232
      connection. Studies of in vitro and in vivo were performed to evaluate the
      biosensor. The linear response of the biosensor is up to 15 mM of glucose in
      vitro. The results of in vivo study show significant glucose variations measured
      from the interstitial tissue fluid of a diabetes rat in fasting and non-fasting
      periods.

PMID- 19163379
TI  - Stratum corneum in vivo water content from TEWL-measurements.
AB  - In this paper we present a new pilot-study on the possibility of finding in vivo
      absolute water content of the stratum corneum (SC) non-invasively. The method is
      based on measurements of trans-epidermal-water-loss (TEWL) after an occlusion
      process of the SC. Based on the desorption curves from the occluded skin,
      estimates of absolute water content of the SC can be made by assuming a similar,
      but hypothetical, desorption of non-occluded SC.

PMID- 19163380
TI  - Development of a magnetic Single Cell Micro Array.
AB  - Experiments using single cells are valuable for revealing individual cell
      behaviour, which is of interest to many biomedical researchers. In such
      experiments, various types of devices capable of aligning cells into organized
      arrays are often used. In this paper, we present a novel Single Cell Micro Array
      device that makes use of magnetic forces. Prototypes of this device have been
      fabricated, and successfully tested using Jurkat cells that have been labelled
      with nano-magnetic particles. Experimental results show that the prototypes are
      effective on capturing and placing the labelled cells in an array.

PMID- 19163381
TI  - Detection of specific bioparticles using antibodies-coated gold nanoparticles and
      dielectrophoretic impedance measurement.
AB  - In this study, we developed an easy and quick test capable of identifying
      specific bacteria in one hour. The protocol was established based on the
      measurement of bacteria quantity on a biochip with comb-like electrodes. Gold
      nanoparticles coated with anti-Salmonella antibody were used to enhance the
      dielectrophretic property of Salmonella spp. on the biochip to facilitate the
      sensitivity.

PMID- 19163382
TI  - Characterization of DNA bio-bonds for meso-scale self-assembly.
AB  - In this paper, we have investigated the use of DNA hybridization as the basis for
      the production of new mesoscale components. AFM experimental results are studied
      and compared to two theoretical approaches: molecular and thermodynamic. We
      explain how and why DNA hybridization process can provide a good bond to self
      assemble components, and how molecular modelling methods allow further
      understanding of the physical mechanism of this process. Furthermore, the
      strength interaction of DNA complementary strands is measured and analyzed using
      statistical tools. These results are then compared to the theoretical approaches.

PMID- 19163383
TI  - Influence of system integration and packaging for a wireless neural interface on
      its wireless powering performance.
AB  - In an integrated wireless neural interface based on the Utah electrode array, the
      implanted electronics is supplied with power through inductive coupling between
      two coils. This inductive power link would be affected by conductive and
      dielectric media surrounding the implant coil. In this study, the influences of
      the integration of implant coil on silicon based IC/electrode, thin film parylene
      coating, and physiological medium surrounding the coil were investigated
      systematically and quantitatively. A few different versions of implant coils were
      made by winding fine wire with a diameter of around 50 microm. The parasitic
      influences affecting the inductive power link were empirically investigated by
      measuring the electrical properties of coils in different configurations and in
      different media. The distance of power transmission between the transmit and
      receive coils was measured when the receive coil was in air and immersed in
      saline solution to simulate an implanted physiological environment. The results
      from this study suggest factors to be considered when integrating and
      encapsulating implantable devices that employ inductive power link.

PMID- 19163384
TI  - The case for a generic implant processor.
AB  - A more structured and streamlined design of implants is nowadays possible. In
      this paper we focus on implant processors located in the heart of implantable
      systems. We present a real and representative biomedical-application scenario
      where such a new processor can be employed. Based on a suitably selected
      processor simulator, various operational aspects of the application are being
      monitored. Findings on performance, cache behavior, branch prediction, power
      consumption, energy expenditure and instruction mixes are presented and analyzed.
      The suitability of such an implant processor and directions for future work are
      given.

PMID- 19163385
TI  - VLSI architecture of leading eigenvector generation for on-chip principal
      component analysis spike sorting system.
AB  - On-chip spike detection and principal component analysis (PCA) sorting hardware
      in an integrated multi-channel neural recording system is highly desired to ease
      the bandwidth bottleneck from high-density microelectrode array implanted in the
      cortex. In this paper, we propose the first leading eigenvector generator, the
      key hardware module of PCA, to enable the whole framework. Based on the iterative
      eigenvector distilling algorithm, the proposed flipped structure enables the low
      cost and low power implementation by discarding the division and square root
      hardware units. Further, the proposed adaptive level shifting scheme optimizes
      the accuracy and area trade off by dynamically increasing the quantization
      parameter according to the signal level.With the specification of four principal
      components/channel, 32 samples/spike, and nine bits/sample, the proposed hardware
      can train 312 channels per minute with 1MHz operation frequency. 0.13 mm(2)
      silicon area and 282microW power consumption are required in 90 nm 1P9M CMOS
      process.

PMID- 19163386
TI  - Harmonics-based bio-implantable telemetry system.
AB  - Miniaturization is a key focus for medically implantable electronics such as
      Cochlear and Retinal prosthesis, and medical monitoring and recording
      applications. The need for low power dissipation is equally important, and power
      hungry crystals and oscillators are commonly used to produce and control the
      implant's carrier transmission frequency. This paper presents a new harmonics
      based method that allows this transmission frequency to be varied and controlled
      externally, while also minimizing the size and power requirements of certain
      implanted devices.

PMID- 19163387
TI  - Development of flexible microelectrode arrays for recording cortical surface
      field potentials.
AB  - The fabrication, characterization and application of an 8-channel flexible
      microelectrode array for recording cortical surface field potentials is
      described. Polyimide-based microelectrode arrays were fabricated by using
      photolithography and physical vapour deposition (PVD) methods. Polyimide was
      chosen as the substrate and insulation material due to its suitable mechanical
      properties and biocompatibility. Electrodes and transmission lines were formed by
      sputter-coating of platinum thin films. Microelectrode arrays were characterized
      and tested successfully in vitro by impedance spectroscopy and in vivo by
      somatosensory evoked potential (SEP) recordings in rats. These tests indicated
      good performance and the potential of microelectrode arrays.

PMID- 19163388
TI  - Implantable telemetry capsule for monitoring arterial oxygen saturation and
      heartbeat.
AB  - In this study, we have developed an implantable telemetry capsule for monitoring
      heartbeat. The capsule has three main functions, monitoring vital signs,
      transmitting the vital signs, and receiving energy for driving the capsule
      without wires. We used two wavelengths of LEDs and a photodiode sensitive to the
      two wavelengths for heartbeat sensor. The arterial oxygen saturation is
      calculated from the amplitude of the heartbeat signal. We fabricated an FM
      transmitter whose carrier frequency was 80 MHz. Though the GHz range frequency is
      generally used in transmission, the attenuation in the human body is large. The
      size of a common linear antenna is about a quarter of its operating wavelength.
      We employed a coil-based antenna which can reduce size below the quarter of the
      wavelength. We fabricated a miniaturized transmitter with the coil-based antenna
      at lower frequency. Our capsule was driven intermittently. We used a rechargeable
      battery. When the battery ran down, the battery was charged by wireless using the
      induced electromotive force. This means that the capsule is capable of monitoring
      vital signs over the long term. We measured the heartbeat from the middle finger
      of hand in a water tank as a model of a human body.

PMID- 19163389
TI  - NO Gas sensor of PEDOT: PSS nanowires by using direct patterning DPN.
AB  - Nitric oxide (NO) detection is a critical issue for environmental safety and
      medical diagnosis due reasons with regard to the toxic properties for human body
      and metabolic index for respiratory disease, respectively. Development of gas
      sensor with high sensitivity is very important because the concentration of NO
      gas in the environment and respiratory tract is extremely low, therefore not
      readily detectable. The material with nanostructure can improve the sensitivity
      of sensor owning to surface effect and size effect. Herein, we developed a new
      type of gaseous nanosensor assembled by 34 nanowires of conducting polymer,
      PEDOT: PSS. The nanowires were fabricated by dip pen nanolithography (DPN) with
      the length of 55 um and diameter of 300 nm between golden wires. The NO gas
      measurement is based on chemiresistor based methods. The result of dynamic
      measurement of NO gas at 100 ppm shows repeatability and stability; the recovery
      time is 10.4 minutes. Moreover, the lowest concentration of NO gas in static
      measurement is 10ppm at 80 C, which also shows the ability sensing at low
      temperature.

PMID- 19163390
TI  - Interconnection technologies for laser-patterned electrode arrays.
AB  - Standard interconnection technologies are reviewed in respect to their
      applicability to electrically and mechanically connect laser-patterned nerve
      electrodes made from silicone rubber and platinum foil to wires and screen
      printed alumina substrates. Laser welding, gap welding, microflex ball bonding,
      and soldering are evaluated. Corresponding processes were established and
      evaluated in respect to their mechanical strength. Best results were obtained by
      soldering. If soldering cannot be used because of regulatory reasons, parallel
      gap welding and microflex are recommended. Laser welding provides weaker
      interconnects with only moderate reproducibility.

PMID- 19163391
TI  - A complete data and power telemetry system utilizing BPSK and LSK signaling for
      biomedical implants.
AB  - In this paper, a prototype of a telemetry system for battery-less biological
      implant is implemented, which demonstrates both wireless power delivery and
      duplex wireless data communication. BPSK (Binary Phase Shift Keying) modulation
      is used for the data transmission from the external controller to the implant and
      LSK (Load Shift Keying) modulation is used for the reverse data transmission from
      the implant to the external controller. Power is being delivered wirelessly to
      the implant through the energy contained in the incoming BPSK data signal. This
      implant system contains a novel single chip realization of low power BPSK
      demodulator architecture, which provides considerable power savings compared to
      prior art. The demodulator occupies 0.1mm(2) area and consumes 5mW power from a
      3.3V power supply. A sensitive board level LSK receiver for data transmitted from
      implant to the external reader has been proposed. External BPSK transmitter
      consists of a class-E power amplifier that serves the dual purpose of a data
      transmitter and wireless power delivery. In summary, a very low power
      bidirectional power and data telemetry system for biological implants based on
      BPSK and LSK signaling is proposed.

PMID- 19163392
TI  - Effect of different breathing patterns on nonlinearity of heart rate variability.
AB  - We studied the effects of different respiratory patterns, namely, spontaneous
      breathing, paced breathing (at a rate of 10 breaths/min and at their mean
      spontaneous breathing frequency) and breath holding, on the nonlinear
      characteristics of heart rate variability (HRV). The results showed that paced
      breathing at both rates significantly diminished the nonlinearity of HRV detected
      by the Volterra-Wiener series method in comparison with spontaneous breathing,
      while breath holding increased it. These findings indicate spontaneous breathing
      rate is probably optimum to maintain cardiopulmonary coupling nonlinearly, and
      thus to minimize the influence on cardiovascular variabilities.

PMID- 19163393
TI  - Unconstrained respiration and heart rate monitoring system based on a PPG pillow
      during sleep.
AB  - In this paper, we have suggested a novel method to monitor respiration and heart
      rate using a PPG pillow during sleep. The proposed method employs a pillow
      containing a reflective type PPG sensor and a simple extraction algorithm. The
      PPG pillow was placed under the back of a neck to acquire PPG signal on the
      assumption that the subjects hardly change their position. The results showed
      considerable coincidence between the extracted respiratory rhythm and the
      reference signal in case of either a medium or a high respiration speed, while it
      was hard to extract the rhythm based on the trace line formed by linear
      interpolating the detected valleys under the condition of a low respiration
      speed. HRV could be alternative to the interpolated trace line in the case. This
      study shows the proposed method has an advantage of processing simplicity so as
      to be used easily in unconstrained respiration and heart rate monitoring.

PMID- 19163394
TI  - Characterization of periodic and non-periodic breathing pattern in chronic heart
      failure patients.
AB  - Periodic breathing (PB) has a high prevalence in chronic heart failure (CHF)
      patients with mild to moderate symptoms and poor ventricular function. This work
      proposes the analysis and characterization of the respiratory pattern to identify
      periodic breathing pattern (PB) and non-periodic breathing pattern (nPB) through
      the respiratory flow signal. The respiratory pattern analysis is based on the
      extraction and the study of the flow envelope signal. The flow envelope signal is
      modelled by an autoregressive model (AR) whose coefficients would characterize
      the respiratory pattern of each group. The goodness of the characterization is
      evaluated through a linear and non linear classifier applied to the AR
      coefficients. An adaptive feature selection is used before the linear and non
      linear classification, employing leave-one-out cross validation technique. With
      linear classification the percentage of well classified patients (8 PB and 18 nPB
      patients) is 84.6% using the statistically significant coefficients whereas with
      non linear classification, the percentage of well classified patients increase to
      more than 92% applying the best subset of coefficients extracted by a forward
      selection algorithm.

PMID- 19163395
TI  - Comparison of positioning methods of a ferromagnetic sphere for magnetic steering
      using 3 T MRI.
AB  - Magnetic steering of an untethered ferromagnetic device in a living body has many
      advantages in the clinical fields. In this paper, the positioning and tracking
      methods of a ferromagnetic sphere have been compared with magnetic resonance
      phantom images obtained with three different imaging sequences, spin echo,
      gradient echo, and selected positive contrast sequences. The position of the
      ferromagnetic sphere has been calculated from the MRI images which have
      susceptibility artifacts caused by the magnetic sphere. We have compared the
      positioning errors among the magnetic sphere images.

PMID- 19163396
TI  - A framework for intraoperative update of 3D deformable models in liver surgery.
AB  - Efficient computer assisted surgery dealing with soft tissues remains a complex
      task. In most cases, the preoperative information such as 3D organ
      reconstructions and the planning built upon are no longer valid during the
      surgical process itself due to the deformations of the organ of interest. In this
      article, we describe the foundation parts of a framework that enables updating
      preoperative 3D models with intraoperative measurements in case of liver
      resection. The technique can be summarized as follows. During the planning stage,
      the discrete skeleton of hepatic veins is created out of the CT-reconstruction.
      It is used at time of surgery as the core component of an elastic registration
      between the model and measured points located on vessels centerline.
      Intraoperative data points are automatically computed from navigated ultrasound
      images with a real-time segmentation method. Our approach was tested on simulated
      and real datasets and has demonstrated to be fast and effective.

PMID- 19163397
TI  - Factors affecting the learning curve in Computer Assisted Total Knee
      Arthroplasty.
AB  - Mathematical modeling of learning curves have been used in industry since 1936.
      The advent of Computer Assisted Total Knee Arthroplasty allows the collection of
      hard data. We present our finding of a statistically significant mathematical
      model relating operative time, body mass index, experience of the surgeon and
      preoperative varus deformity in a prospective study of 241 computer assisted
      total knee arthroplasties. To the best of our knowledge, such a model has not
      been described before.

PMID- 19163398
TI  - Haptic control with environment force estimation for telesurgery.
AB  - Success of telesurgical operations depends on better position tracking ability of
      the slave device. Improved position tracking of the slave device can lead to
      safer and less strenuous telesurgical operations. The two-channel force-position
      control architecture is widely used for better position tracking ability. This
      architecture requires force sensors for direct force feedback. Force sensors may
      not be a good choice in the telesurgical environment because of the inherent
      noise, and limitation in the deployable place and space. Hence, environment force
      estimation is developed using the concept of the robot function parameter matrix
      and a recursive least squares method. Simulation results show efficacy of the
      proposed method. The slave device successfully tracks the position of the master
      device, and the estimation error quickly becomes negligible.

PMID- 19163399
TI  - Efficient force feedback transmission system for tele surgery.
AB  - Remote surgery information requires quick and reliable transmission between the
      surgeon and the patient side. However, the interconnecting network is usually
      time varying and lossy which can cause packet loss and delay jitter. In this
      paper we introduce an adaptive packet prediction and buffer time adjustment
      algorithm which reduces the negative effects caused by the time varying networks
      on the transmission of force feedback data. To evaluate our scheme we run a
      virtual reality applet built in Matlab. Our results show, for severe packet loss
      and variable delay jitter, the integrated synchronization technique significantly
      improves the performance of the force feedback device.

PMID- 19163401
TI  - Simulation of organ deformation using boundary element method and meshless shape
      matching.
AB  - In this paper, a novel approach to perform real-time simulation of the
      deformation of anatomical organs is proposed for virtual surgery study. The
      method, which is both physics and interactivity motivated, is composed of two
      algorithms: boundary element method and meshless shape matching. We employ
      boundary element method to simulate a precise global deformation, and use
      meshless shape matching method to achieve low latency. In addition, a state
      machine is applied to control the computation patterns of deformation. The
      initial experiment reveals that the proposed approach can simulate organ
      deformations both efficiently and accurately.

PMID- 19163400
TI  - Epidural insertion simulator of higher insertion resistance & drop rate after
      puncture.
AB  - Accidents such as dural puncture remain one of the problems of epidural
      anesthesia, and unskilled doctors can repeat such accidents. The purpose of the
      current research was to provide a new simulator for epidural insertion training.
      No reference data regarding the resistance force used when inserting a needle
      into patients have been reported. A comparative study was conducted to aid in the
      development of a new simulator. Pork loin (n=5) were employed as a substitute for
      patients. Thickness was set at 2 cm so as to improve the reproducibility. The
      authors took the conventional simulator apart, and picked a block as an analogue
      of muscle and ligamentum flavum. A new simulator was made of a melamine foam
      resin block and a latex rubber sheet. An epidural needle fixed on a motorized
      stage was inserted at the speed of 2 mm per second. The reaction force was
      measured while the needle was inserted into each specimen. Waveform of the pork
      loin exhibited two slopes of different inclines up to peaks and then falls after
      puncture. The conventional simulator showed a simple increase up to peak and a
      slow fall after puncture. In contrast, the new simulator showed two slopes up to
      peak and then a sudden fall after puncture. The insertion resistances were 2.5
      N/s for the porcine, 0.8 N/s for the conventional and 2.1 N/s for the new
      simulator. The drop rates were 5 N/s for the porcine, 0.6 N/s for the
      conventional and 24 N/s for the new simulator. The higher insertion resistance
      and drop rate for the new simulator than the conventional simulator will be
      suitable for epidural insertion training.

PMID- 19163402
TI  - Rapid motion compensation for prostate biopsy using GPU.
AB  - Image-guided procedures have become routine in medicine. Due to the nature of
      three-dimensional (3-D) structure of the target organs, two-dimensional (2-D)
      image acquisition is gradually being replaced by 3-D imaging. Specifically in the
      diagnosis of prostate cancer, biopsy can be performed using 3-D transrectal
      ultrasound (TRUS) image guidance. Because prostatic cancers are multifocal, it is
      crucial to accurately guide biopsy needles towards planned targets. Further the
      gland tends to move due to external physical disturbances, discomfort introduced
      by the procedure or intrinsic peristalsis. As a result the exact position of the
      gland must be rapidly updated so as to correspond with the originally acquired 3
      D TRUS volume prior to biopsy planning. A graphics processing unit (GPU) is used
      in this study to compute rapid updates performing 3-D motion compensation via
      registration of the live 2-D image and the acquired 3-D TRUS volume. The parallel
      computational framework on the GPU is exploited resulting in mean compute times
      of 0.46 seconds for updating the position of a live 2-D buffer image containing
      91,000 pixels. A 2x sub-sampling resulted in a further improvement to 0.19
      seconds. With the increase in GPU multiprocessors and sub-sampling, we observe
      that real time motion compensation can be achieved.

PMID- 19163403
TI  - Motion prediction for tracking the beating heart.
AB  - In the past few years, several research groups have worked on the design of
      efficient motion compensation systems for cardiac robotic-assisted Minimally
      Invasive Surgery (MIS). By providing surgeons with a stabilized work environment,
      significant improvements of the precision and repeatability of their gestures can
      be achieved. The design of a motion compensation system requires the accurate
      measurement of the heart motion, which can be achieved using computer vision
      techniques for tracking cardiac structures on the heart surface. However, most
      works in the literature focus on the representation and localization of cardiac
      structures while few explore their motion dynamics. In this paper we study and
      implement different adaptive methods for predicting the future heart motion using
      Kalman filtering. By exploiting the quasi-periodic nature of the heart motion, we
      are able to increase tracking robustness and computational efficiency. The
      experimental results indicate the significant increase in tracking performance
      when heart motion prediction is employed.

PMID- 19163404
TI  - Control of fracture reduction robot using force/torque measurement.
AB  - We have developed a surgical robotic system for femoral fracture reduction
      employing indirect traction. Indirect traction in fracture reduction is a
      generally used surgical method for preventing complications such as bone splits
      caused by high stress on bones. For traction, a patient's foot is gripped by a
      jig and pulled to the distal side. Indirect traction has the advantage of
      distributing bone stress by utilizing a strong traction force; however, this
      procedure does not accurately control the proper positioning of fractured
      fragments when a surgical robot is used. The human leg has knee and an ankle
      joints, and thus robotic motion presents problems in not being able to directly
      propagate reduction motion to a fractured femoral fragment, rendering control of
      bone position difficult. We propose a control method for fracture reduction
      robots using external force/torque measurements of the human leg to achieve
      precise fracture reduction. Results showed that the proposed method reduced
      repositioning error from 6.8 mm and 15.9 degrees to 0.7 mm and 5.3 degrees,
      respectively.

PMID- 19163405
TI  - A navigation system of cerebral endovascular surgery integrating multiple space
      guiding trackers.
AB  - In this paper, a navigation system combining multiple space-guiding trackers is
      proposed for cerebral endovascular surgery. This system not only provides 2-D and
      3-D visualization of medical images but also integrates an ICP-based algorithm to
      increase the registration accuracy during cerebral endovascular navigation. This
      tracking system integrates a mechanical digitizer, an optical tracker and an
      electromagnetic sensor to increase the flexibility in clinical application. An
      ICP-based registration algorithm is proposed to dynamically correct the
      registration error according to the current observation of the cerebral
      endovascular. To evaluate the system performance, a plastic phantom with cerebral
      endovascular structures is used and the experimental results show that the
      localization error is significantly reduced from 5.21 approximately 6.47mm to
      2.29 approximately 2.87mm using the proposed scheme.

PMID- 19163406
TI  - Highly articulated robotic probe for minimally invasive surgery.
AB  - We have developed a novel highly articulated robotic probe (HARP) that can thread
      through tightly packed volumes without disturbing the surrounding tissues and
      organs. We use cardiac surgery as the focal application of this work. As such, we
      have designed the HARP to enter the pericardial cavity through a subxiphoid port.
      The surgeon can effectively reach remote intrapericardial locations on the
      epicardium and deliver therapeutic interventions under direct control. Our device
      differs from others in that we use conventional actuation and still have great
      maneuverability. We have performed proof-of-concept clinical experiments to give
      us preliminary validation of the ideas presented here.

PMID- 19163407
TI  - Development of thermal model in a child and its application to dosimetry due to
      RF whole-body exposures.
AB  - In this study, we developed a thermal model for children to simulate body-core
      temperature elevation. In comparison of measured and simulated temperatures, the
      thermoregulation in a child was reasonable to consider the same as in the adult.
      Based on this finding, we calculated the body-core temperature elevation in the 3
      year child and adult for plane wave exposure at the basic restriction in the
      international safety guidelines. The body-core temperature elevation in the 3
      year child model was 0.03 degrees C at the whole-body averaged specific
      absorption rate of 0.08 W/kg, which was 35% smaller than in the adult female.
      This difference is attributed to the ratio of the body surface area to the mass.

PMID- 19163409
TI  - The development of a blood pressure simulator in KRISS.
AB  - Blood pressure is defined as the amount of force at unit area which the blood
      exerts on a wall of a blood vessel. The BP has a clinical importance as the basic
      index in the medical examination of patients. Especially, the percentage of the
      hypertensive is more than 15% in an adult population of Korea and hypertension is
      notorious as 'a silent killer' because it has no prior symptoms. The most
      important thing in the diagnosis, treatment and prognosis of hypertension is the
      accurate measurement of the BP. In this study, we developed the blood pressure
      simulator for the monitoring of oscillometric BP devices and compared this KRISS
      simulator with commercial simulators. Finally, we tested the commercial
      oscillometric BP devices (6 models from 5 manufacturers) using the KRISS
      simulator. The KRISS simulator has the repeatability error below 0.1% for the
      pressure generation and we expected to develop the BP simulator for Korean by the
      collection of clinical data from Koreans.

PMID- 19163408
TI  - Computer-assisted orthopedic diagnosis and preoperative planning system based on
      the integrated electronic patient record.
AB  - Computer-assisted orthopedic diagnosis and preoperative planning have been
      recognized as efficient tools to improve the accuracy of clinic diagnosis and
      surgical procedure. In orthopedic clinic, such practices are heavily relied on
      the patient-specific medical image data.

PMID- 19163410
TI  - Photon spectra calculation for an Elekta linac beam using experimental scatter
      measurements and Monte Carlo techniques.
AB  - The present work is centered in reconstructing by means of a scatter analysis
      method the primary beam photon spectrum of a linear accelerator. This technique
      is based on irradiating the isocenter of a rectangular block made of methacrylate
      placed at 100 cm distance from surface and measuring scattered particles around
      the plastic at several specific positions with different scatter angles. The
      MCNP5 Monte Carlo code has been used to simulate the particles transport of mono
      energetic beams to register the scatter measurement after contact the attenuator.
      Measured ionization values allow calculating the spectrum as the sum of mono
      energetic individual energy bins using the Schiff Bremsstrahlung model. The
      measurements have been made in an Elekta Precise linac using a 6 MeV photon beam.
      Relative depth and profile dose curves calculated in a water phantom using the
      reconstructed spectrum agree with experimentally measured dose data to within 3%.

PMID- 19163411
TI  - The application of the movement classification system in the diagnosis of
      children with Cerebral Palsy.
AB  - Cerebral Palsy is mean damage to the brain, causing non-progressive brain injury,
      such as hemiplegia, limbs palsy, epilepsy, involuntary movements, poor
      coordination. This paper proposes a movement evaluation and classification
      system, in view Cerebral Palsy children hand movement smoothness evaluation. In
      addition, the application of the movement classification system in the diagnosis
      of children with cerebral palsy is also discussed. The system contains: image
      capture, image segmentation, and information classification processing. Momentum
      analysis parameters and coordination neural network are used to conduct the data
      classification. The experimental results are shown that the proposed system has
      the higher accurate diagnostic rate of children are divided into cerebral palsy
      groups or normal groups.

PMID- 19163412
TI  - Predicting occurrences of acute hypoglycemia during insulin therapy in the
      intensive care unit.
AB  - As intensive care units (ICUs) implement more intense insulin therapy to achieve
      tighter glycemic control, the risk for ICU patients to experience acute
      hypoglycemia increases. This study aims to develop a new method for predicting
      the occurrences of acute hypoglycemia during intravenous (IV) insulin infusion
      before the actual hypoglycemic events take place. Data from 3116 adult ICU
      patients have been retrospectively analyzed to elucidate glycemic dynamics and to
      devise a methodology for proactive prediction of acute hypoglycemic events in the
      ICU. Mutual information, embedded selection by classification trees, and odds
      ratios of categorized clinical time-series and occurrences of acute hypoglycemia
      were used to compare features of patients' glycemic dynamics. Classification tree
      learning was then applied to key features to generate predictive models of acute
      hypoglycemia. Results show that the two most recent blood glucose measurements
      and the slope of recent changes in blood glucose concentration with respect to
      the change in insulin infusion are the most informative features. Classification
      tree models built upon the key features accurately predicted 82.12% of acute
      hypoglycemic events (specificity: 89.87%; positive predictive value: 88.72%;
      accuracy: 86.00%) and 76.99% of severe acute hypoglycemic events (80.53%, 74.31%,
      and 78.76% respectively). The mechanistic approach developed in this study could
      be useful to discovering and understanding trends in clinical data leading up to
      acute hypoglycemia.

PMID- 19163413
TI  - A new venous infusion path monitoring system utilizing electrostatic induced
      potential.
AB  - A new venous infusion pathway monitoring system has been developed for hospital
      and home use. The system consists of linear and digital integrated circuits and a
      low-power 8-bit single chip microcomputer which constantly monitors the infusion
      pathway intactness. A 330 kHz AC voltage, which is induced on the patient's body
      by electrostatic coupling from a 330 kHz pulse oscillator, can be recorded by
      main and reference electrodes wrapped around the infusion polyvinyl chloride
      tube. If the injection needle or infusion tube becomes detached, then the system
      detects changes in the induced AC voltages and alerts the nursing station, via
      the nurse call system or PHS (personal handy phone system).

PMID- 19163414
TI  - Personalisation and configuration of assistive technologies.
AB  - In this paper we present a multimedia tool that allows personalisation and
      configuration of an assistive technology. We have developed a tool called HomePUI
      that allows configuration of three disease domains; cognitive, physical and
      chronic. In this paper we present the rationale for our work, details of the
      developed tool and also present two case studies in which the tool has been used
      within cognitive and chronic disease management domains.

PMID- 19163415
TI  - Personalized healthcare through intelligent gadgets.
AB  - An intelligent gadget is a wearable platform which is reconfigurable, scalable,
      and component-based and which can be equipped, carried as a personal accessory,
      or in a certain case, implanted internally into a body. Various kinds of personal
      information can be gathered with intelligent gadgets, and that information is
      used to provide specially personalized services to people in the ubiquitous
      computing environment. In this paper, we show a personalized healthcare service
      through intelligent gadgets. A service based on intelligent gadgets can be built
      intuitively and easily with a context representation language, called the
      intelligent gadget markup language (IGML) based on the event-condition-action
      (ECA) rule. The inherent nature of extensibility, not only environmental
      information but also physiological information can be specified as a context in
      IGML and can be dealt with an intelligent gadget with ease. It enables
      intelligent gadgets to be adopted to many different kinds of personalized
      healthcare services.

PMID- 19163416
TI  - Home-based cognitive monitoring using embedded measures of verbal fluency in a
      computer word game.
AB  - Verbal fluency is a standard neuropsychological test that measures the ease with
      which a person can produce words. It is commonly used in the diagnosis and
      characterization of cognitive disorders. In this paper, we describe a method for
      measuring a proxy for verbal fluency from embedded metrics within a computer word
      game. We evaluated our ability to monitor verbal fluency metrics over a period of
      one year in 30 elderly subjects by analyzing their computer game play. We found
      good correspondence between these computer metrics and the scores from standard
      verbal fluency assessments.

PMID- 19163417
TI  - Health smart home for elders - a tool for automatic recognition of activities of
      daily living.
AB  - Elders live preferently in their own home, but with aging comes the loss of
      autonomy and associated risks. In order to help them live longer in safe
      conditions, we need a tool to automatically detect their loss of autonomy by
      assessing the degree of performance of activities of daily living. This article
      presents an approach enabling the activities recognition of an elder living alone
      in a home equipped with noninvasive sensors.

PMID- 19163418
TI  - Detection abnormal pattern in activities of daily living using sequence alignment
      method.
AB  - As the aging is rapidly coming, the necessity of cares for old people increases.
      As requests for care services for patients requiring help of others increases,
      various systems for care services have been developed. For care services,
      recently, there have been developed technologies of tracking and monitoring daily
      activities of a person and recognizing the daily activities of the person by
      analyzing tracked data. Particularly, there have been developed systems for
      taking care of a person whose state should be periodically checked, such as
      patients or old persons. General care systems are good for tracking what activity
      the person executes, but limited to detecting what a person's state is, such as a
      normal or an abnormal state. So it is necessary to develop a new computational
      method to detect abnormal signs in a life pattern via changes of a sequence of
      activities of daily living.

PMID- 19163419
TI  - HomeADL for adaptive ADL monitoring within smart homes.
AB  - In this paper we present homeADL: a representation standard for an inference
      hierarchy of activities of daily living which may be monitored in a sensor
      equipped smart home. The approach allows a free exchange of ADL monitoring
      structures between different communities who share the same concern of providing
      high quality healthcare to the elderly. Its ability of matching different ADL
      protocols enables a mapping between an ADL protocol to a suitable smart home
      which makes an effective management of smart homes within a community hence, not
      only being able to satisfy an individual's healthcare requirements but also
      efficiently using monitoring resources at hand.

PMID- 19163420
TI  - Level of activity, night and day alternation, and well being measured in a smart
      hospital suite.
AB  - The present paper reports a study on the daily activity of elderly people in a
      hospital suite, with presence infrared sensors. It is an attempt to produce
      parameters and indicators for the predictive analysis of the daily activity of
      fragile persons. A relationship is proposed between well being of the patient and
      the night and day activities alternation.

PMID- 19163421
TI  - The inescapable smart impact detection system (ISIS): An ubiquitous and
      personalized fall detector based on a distributed 'divide and conquer strategy'.
AB  - Despite the intense research in the last decade with the aim of developing a
      reliable solution for fall detection in the elderly and other risk populations,
      it can be asserted that the diffusion of fall detectors in the geriatric practice
      is near null. This scenario is similar to the very scarce use of telemedicine in
      healthcare. The present work begins analyzing why fall detectors have not
      achieved to permeate the industry. That road is used to know the drawbacks of
      current devices and systems, besides to allow studying several important concepts
      underlying the principles of fall detection. A novel smart detection system based
      on that survey is finally briefly presented. The design of this device is founded
      on the experience and results obtained by an earlier device that was designed in
      the framework of the thesis of one of the authors.

PMID- 19163422
TI  - Contrasting spatial, temporal and spatio-temporal ICA applied to ictal EEG
      recordings.
AB  - In this paper we contrast three implementations of Independent Component Analysis
      (ICA) as applied to epileptic scalp electroencephalographic (EEG) recordings,
      these are; Spatial (Ensemble) ICA, Temporal (single-channel) ICA and Spatio
      Temporal ICA. These techniques are based on information derived from both multi
      channel as well as single channel biomedical signal recordings. We assess the
      suitability of the three techniques in isolating and extracting out epileptic
      seizure sources. Although our results are preliminary in nature, we show that
      standard implementations of ICA (ensemble ICA) are lacking when attempting to
      extract complex underlying activity such as ictal activity in the EEG. Temporal
      ICA performs well in separating underlying sources, although it is clearly
      lacking in spatial information. Spatio-Temporal ICA has the advantage of using
      temporal information to inform the ICA process, aided by the spatial information
      inherent in multi-channel recordings. This work is being expanded for seizure
      onset analysis through scalp EEG.

PMID- 19163423
TI  - Cumulant matching for independent source extraction.
AB  - In this work we show how one can make use of priors on signal statistics under
      the form of cumulant guesses to extract an independent source from an observed
      mixture. The advantage of using statistical priors on the signal lies in the fact
      that no specific knowledge is needed about its temporal behavior, neither about
      its spatial distribution. We show that these statistics can be obtained either by
      reasoning on the theoretical values of a supposed waveform, either by using a
      subset of the observations from which we know that their statistics are merely
      hindered by interferences. Results on an electro-cardiographic recording confirm
      the above assumptions.

PMID- 19163424
TI  - Robust independent component analysis for blind source separation and extraction
      with application in electrocardiography.
AB  - The problems of signal separation and signal extraction arise in a wide variety
      of applications in biomedical engineering and other areas. Under the source
      statistical independence assumption, these problems can be solved by independent
      component analysis (ICA) methods. A simple ICA technique, referred to as
      RobustICA, has recently been proposed that shows interesting features such as
      very fast convergence, local-extrema escaping capabilities and the possibility of
      avoiding prewhitening. The present contribution explains how RobustICA can easily
      be modified to target particular sources according to their impulsive character
      as measured by the kurtosis sign. This new feature makes it possible to extract
      the sources of interest only, or a subspace thereof, with the subsequent
      reduction in computational complexity and error accumulation. The performance of
      this modification is illustrated on signal recordings issued from
      electrocardiography.

PMID- 19163425
TI  - Model order estimation for blind source separation of multichannel
      magnetoencephalogram and electroencephalogram signals.
AB  - Most blind source separation (BSS) approaches - especially independent component
      analysis (ICA) - assume a noiseless mixture of the same number of sources as
      sensors. It is doubtful, however, whether this assumption actually holds for
      multichannel magnetoencephalogram (MEG) and electroencephalogram (EEG)
      measurements comprising a large number of channels. Corroborating and extending
      previous results, this work further examines the utility of second-order
      statistical methods based on probabilistic principal component analysis (PPCA)
      and factor analysis (FA) models for estimating the number of underlying sources
      in multichannel MEG and EEG. Compared with conventional PCA-based eigenvalue
      thresholding, both PPCA and FA approaches yield stable model order estimates
      which are almost independent of total signal power. The FA model provides a more
      optimal description of both MEG and EEG data than PPCA, in terms of balancing
      goodness-of-fit and parsimony. These findings add to the growing evidence that
      anisotropic 'sensor noise' may be a statistically robust characteristic of both
      the EEG and MEG, which most BSS algorithms and applications do not address.

PMID- 19163426
TI  - Localization and control of activity in peripheral nerves.
AB  - Interest in the field of the natural control of human limb using physiological
      signals has risen dramatically in the past 20 years due to the success of the
      brain machine interface. Cortical signals carry significant information but are
      difficult to access. The peripheral nerves of the body carry both command and
      sensory signals and are far more accessible. While numerous studies have
      documented the selective stimulation properties of, conventionally round, nerve
      cuff electrodes (i.e., transverse geometry) and even self-sizing electrodes,
      recording the activity levels from individual fascicles using these electrodes is
      still an unsolved problem. Moreover, the control algorithms for the control of
      joint movement with multiple contact electrodes such as the flat interface nerve
      electrode (FINE) have been difficult to implement. We propose solutions to both
      these problems by using beam forming techniques to detect the location and the
      activity in various fascicles. We also developed a control algorithm that
      separates the dynamic from the passive properties to solve the redundancy problem
      in multiple joint problems. This techniques could find application in the natural
      control of artificial limbs from peripheral nerve signals for patients with
      amputated limbs or to restore function in patients with stroke or paralyzed
      limbs.

PMID- 19163427
TI  - Functional neuroimaging of dynamic brain activation.
AB  - Brain activation is distributed in 3-dimensional brain and evolves in time. This
      paper reviews our recent work on developing high resolution spatio-temporal
      functional neuroimaging methods.

PMID- 19163428
TI  - Hafnium transistor design for neural interfacing.
AB  - A design methodology is presented that uses the EKV model and the g(m)/I(D)
      biasing technique to design hafnium oxide field effect transistors that are
      suitable for neural recording circuitry. The DC gain of a common source amplifier
      is correlated to the structural properties of a Field Effect Transistor (FET) and
      a Metal Insulator Semiconductor (MIS) capacitor. This approach allows a
      transistor designer to use a design flow that starts with simple and intuitive 1
      D equations for gain that can be verified in 1-D MIS capacitor TCAD simulations,
      before final TCAD process verification of transistor properties. The DC gain of a
      common source amplifier is optimized by using fast 1-D simulations and using
      slower, complex 2-D simulations only for verification. The 1-D equations are used
      to show that the increased dielectric constant of hafnium oxide allows a higher
      DC gain for a given oxide thickness. An additional benefit is that the MIS
      capacitor can be employed to test additional performance parameters important to
      an open gate transistor such as dielectric stability and ionic penetration.

PMID- 19163429
TI  - Contactless diamagnetic trapping of living cells onto a micromagnet array.
AB  - This paper focuses on the application of magnetophoresis to a new cell patterning
      method. The principle was demonstrated by using a CoPt micromagnet array,
      producing regularly spaced magnetic traps where cells were confined without any
      contact under the effect of negative magnetophoresis. To obtain this effect,
      yeast cells (Saccharomyces cerevisiae), which are diamagnetic, were placed in an
      aqueous solution enriched in paramagnetic ions. Unlabeled (non-magnetic) cell
      manipulation by magnetophoresis requires the production of high magnetic field
      gradients, ensuring significant forces. Therefore, micromagnets are particularly
      interesting for our application, since the field gradient increases as magnet
      dimensions are reduced.

PMID- 19163430
TI  - Piezo motor based microdrive for neural signal recording.
AB  - The miniature piezo motor based microdrive which is applicable to the neural
      signal recording in mice is presented. The microdrive is manipulated by the
      micromotion of the mobile coupled to the piezo motor generating the flexural
      vibration within the range of 3.8 mm, with the resolution of 60nm. Advancement of
      electrodes in a mouse brain is monitored by an integrated MR (Magneto-Resistive)
      sensor. This microdrive has the length of 6.5mm, the width of 6.5 mm, the height
      of 12 mm and the total weight of 1.63 g only, including PCB for neural signal
      recording. The displacement of the microelectrode was evaluated and verified as
      applying the inputs with 5 to 100 pulses, 30 times to the piezo motor according
      to various driving voltages. The neural signals from the single thalamic neurons
      in an awake and freely moving mouse were recorded successfully with the presented
      microdrive.

PMID- 19163431
TI  - Highly sensitive immunosensor using a nanofluidic preconcentrator.
AB  - This paper presents a micro-/nanofluidic biochip for enhanced sensitivity of
      immunoassay. By using a protein preconcentrator based on nanofluidic filters, we
      greatly improve the binding kinetics of immunoassay. A shallow nanofluidic
      channel connecting two microchannels for ion-selective filter is etched on the
      glass surface and sealed by PDMS/Glass irreversible bonding treated with O2
      plasma. Our device achieved a 10(5) fold increase in protein concentration with
      12 minutes of preconcentration. For applying the preconcentrator to immunoassay,
      we fabricated a novel device with a thin layer of Au sputtered near the
      nanochannel to provide a substrate for antibody immobilization and a sensing area
      at the site of highly concentrated proteins. After increasing the concentration
      of antibody and target antigen by multiple sample preconcentration steps, the
      binding kinetics of immunoassay can be significantly improved.

PMID- 19163432
TI  - Evaluation of cortical visual prostheses microelectrode array function.
      Description of behavioral feline model.
AB  - Felines are highly organized mammals with relatively similar to human structure
      functional visual system and they are able to create reflex behavior in response
      to specific stimulus. Thus, feline model seems to be valuable in checking
      microelectrode array function in visual prosthetic device before experimenting in
      human. We believe that reflex behavior developed by cats in our experiment of
      response to electric stimulus delivered from microelectrode array is a response
      to phosphenes, similar to light stimulus response.

PMID- 19163433
TI  - Feedback control of retrograde peristalsis using Neural Gastric Electrical
      Stimulation.
AB  - Neural Gastric Electrical Stimulation (NGES) is a new method for invoking gastric
      contractions under microprocessor control. However, optimization of this
      technique using feedback mechanisms to minimize power consumption and maximize
      effectiveness has been lacking. The present work proposes a prototype feedback
      controlled neural gastric electrical stimulator for the treatment of obesity.
      Both a force-based and an interelectrode impedance-based feedback neurostimulator
      were implemented and tested. Four mongrel dogs (2 M, 2 F, weight 14.9 ++/- 2.3kg)
      underwent subserosal implantation of 2-channel 1-cm bipolar electrode leads in
      the distal antrum. Two of the dogs were stimulated with a force-based feedback
      system and the other two animals were stimulated utilizing an interelectrode
      impedance-based feedback system. Both feedback systems were able to recognize
      Erythromycin-driven contractions of the stomach and were capable of overriding
      them with NGES-invoked retrograde contractions. The proposed technique could be
      helpful for retaining food longer in the stomach, thus inducing early satiety and
      diminishing food intake.

PMID- 19163435
TI  - Real-time myocardial segmentation using coupled active geometric functions.
AB  - Myocardial segmentation is essential for quantitative evaluation of cardiac
      functional images. As imaging techniques advance, 3D and 4D image data have
      become available. These data can provide clinically important cardiac dynamic
      information at high spatial or temporal resolution. However, the enormous amount
      of information contained in these data has also raised a challenge for
      traditional image analysis algorithms in terms of efficiency and clinical
      workflow. In this context, an automated real-time myocardial segmentation
      framework based on coupled Active Geometric Functions was proposed and tested on
      414 frames of Phase Train Imaging data, a real-time cardiac MR imaging technique,
      with an average temporal resolution of 2 ms. The performance of myocardial
      segmentation was visually and quantitatively validated. Implemented in Matlab(c),
      the current method takes less than 1.2 ms per cardiac phase, allowing realization
      of true real-time online segmentation.

PMID- 19163434
TI  - Real-time cardiac MRI without triggering, gating, or breath holding.
AB  - State-of-the-art cardiac MRI can perform real-time 2D scans without cardiac
      triggering during a single breath hold; however, real-time cardiac MRI in rats is
      difficult due to the high heart rate (330 bpm) and presence of respiratory
      motion. These challenges are overcome by using a dynamic imaging method based on
      Partially Separable Function (PSF) theory with an acceleration factor of 256.
      This paper demonstrates that this method can be used in the study of transplanted
      rat hearts for both anatomical and perfusion applications. The study was carried
      out with a 200 microm in-plane resolution with a 17.2 msec temporal resolution,
      and the results show improved spatial resolution (2x) and reduced acquisition
      time (3x) relative to Electrocardiogram (ECG) triggered, respiratory gated cine
      imaging.

PMID- 19163436
TI  - A new similarity measure for non-rigid breathing motion compensation of
      myocardial perfusion MRI.
AB  - Breathing movements during the image acquisition of first-pass gadolinium
      enhanced, myocardial perfusion Magnetic Resonance Imaging (MRI) hinder a direct
      automatic analysis of the blood flow of the myocardium. In addition, a
      qualitative readout by visual tracking is more difficult as well. Non-rigid
      registration can be used to compensate for these movements in the image series.
      Because of the local contrast and intensity change over time, the registration
      criterion needs to be chosen carefully. We propose a measure based on Normalized
      Gradient Fields (NGF) in order to obtain registration. Since this measure
      requires strong gradients in the images, we also test combining the measure with
      the Sum of Squared Differences (SSD) to maintain registration forces over the
      whole image area. To ensure smoothness, we employ a Laplacian regularizer and use
      the B-spline based approach to describe the transformation of the image space.
      Our experiments show that by using NGF good registration results can be obtained
      for image exhibiting a high intensity contrast. For images with a low intensity
      contrast, combining NGF and SSD improves the registration results significantly
      over using NGF only. Both measures are differentiable making possible the
      application of fast, gradient based optimizers.

PMID- 19163437
TI  - Background noise removal in cardiac magnetic resonance images using Bayes
      classifier.
AB  - Imaging of the heart anatomy and function using magnetic resonance imaging (MRI)
      is a powerful tool for diagnosing a number of heart diseases. Recently, a
      technique was developed to acquire cine sequence of the heart that generates a
      null (black) signal intensity for the blood aiming to increase the image contrast
      to-noise ratio between the myocardium and the background. Nevertheless, the
      technique inherently suffers from elevated noise level which limits the contrast
      to-noise ratio. In this work, a probabilistic model for blood and tissue signals
      is developed and used to build a Bayes decision function. The Bayes classifier is
      then used to identify and filter out the background signal. Numerical simulation
      and real MRI data are used to test and validate the proposed method. The results
      show that the proposed method can increase the contrast-to-noise ratio by a
      factor of four.

PMID- 19163438
TI  - A regularized flow quantification method using MRI tagging and Single Echo
      Acquisition imaging.
AB  - Single Echo Acquisition (SEA) imaging is a fully parallel imaging method that can
      be used to image rapid flow at the frame rate as high as 200 frames per second.
      Previous work has shown that SEA imaging can visualize turbulent flows, and
      discussed a preliminary tool for quantitatively analyzing 2D rapid fluid flows
      using SEA imaging and the HARmonic Phase (HARP) method. In this paper, the
      quantification method was further developed to use physical model to constrain
      the HARP flow analysis. Specifically, the method uses Navier-Stokes and
      continuity equations to regularize the flow analysis. The method is applied to
      the tagged SEA MR image sequence of turbulent flows to test its effectiveness.
      The results from the new method was demonstrated and compared with the flow field
      obtained from the conventional HARP method.

PMID- 19163439
TI  - Assessment of myocardial deformations from untagged cardiac cine MRI.
AB  - This paper presents a method for the assessment of left ventricular myocardial
      deformations from untagged cardiac cine MRI. Firstly, a level set segmentation
      process is applied on the dataset to detect both endocardial and epicardial
      boundaries. Then the successive contours are matched using an original procedure
      that consists in an alignment followed by a morphing process. From the matched
      contours, we deduced an initial velocity of the contour points that will be used
      in a Thin-Plate Splines approximation method for estimating of the velocity flow
      on the complete myocardial structure. Finally, local measurements of ventricular
      deformations are derived from the velocity flow. The validation of the method is
      performed both mathematically and by comparing the measurements to those obtained
      on the same patients with the HARmonic Phase reference (HARP) method applied on
      matched tagged MR images.

PMID- 19163440
TI  - Use of relaxation time as a marker for arterial distensibility.
AB  - Arterial stiffening is associated with a number of known cardiovascular risk
      factors, including advancing age, increased systolic blood pressure (SBP),
      diabetes, hypertension, heart failure, myocardial infarction, and obesity. Many
      methodologies, both invasive and noninvasive, have been applied to the assessment
      of the stiffening of large elastic arteries in vivo, but there is no economically
      and/or universally accepted means of screening patients for atherosclerosis. From
      preliminary studies, a novel parameter, arterial relaxation time, has been
      identified as a potential indicator for inferring the elasticity of arteries.
      Preliminary measurements of arterial relaxation time of six normotensive subjects
      are significantly less than measurements of four hypertensive subjects.

PMID- 19163441
TI  - Semantic wireless body area networks.
AB  - In this paper we introduce the concept of semantic Wireless Body Area Network
      (sWBAN). First the method for semantic interpretation of body sensor data is
      developed. This method is then illustrated for the case of ECG monitoring,
      providing the user with real-time monitoring and interpretation of heart
      activity. Finally, possible extensions of the method to data fusion and context
      aware monitoring are discussed.

PMID- 19163442
TI  - Low data rate ultra wideband ECG monitoring system.
AB  - This paper presents a successfully implemented wireless electrocardiograph
      monitoring using low data rate ultra wideband (UWB) transmission. Low data rate
      ultra wideband is currently under consideration for the newly formed wireless
      body area network (WBAN) group (IEEE802.15.6) to develop a standard for wireless
      vital sign monitoring. Maximizing the transmission power of the transmitter and
      reducing the stringent requirements and complexity of the receiver have always
      been the key considerations for an UWB transceiver. Multiple pulses per bit has
      been sent in our low data rate UWB prototype system to increase the transmitter
      power, to reduce the complexity of the receiver and to ease the requirement on
      the receiver's analog to digital converter. Non-coherent technique has been used
      for the demodulation of UWB signals at the receiver that reduces the receiver
      complexity further.

PMID- 19163443
TI  - Implementation of body area networks based on MICS/WMTS medical bands for
      healthcare systems.
AB  - A multi-hoping sensor network system has been implemented to monitor
      physiological parameters from multiple patient bodies by means of medical
      communication standards MICS (Medical Implant Communication Service) and WMTS
      (Wireless Medical Telemetry Service). Unlike the other medical sensor networks
      (they usually use 2.4 GHz ISM band), we used the two medical standards occupying
      the frequency bands that are mainly assigned to medical applications. The
      prototype system uses the MICS band (402-405 MHz) between the sensor nodes and a
      remote central control unit (CCU). And WMTS frequencies (608-614MHz) are used
      between the CCUs and the remote base stations allowing for a much larger range
      acting as an intermediate node. The sensor nodes in the prototype can measure up
      to four body signals (i.e. 4-channel) where one is dedicated to a continuous
      physiological signal such as ECC/EEG. The system includes firmware and software
      designs that can provide a long distance data transfer through the internet or a
      mobile network.

PMID- 19163444
TI  - Wireless Body Sensor Network for low-power motion-tolerant synchronized vital
      sign measurement.
AB  - Prophylaxis and rehabilitation of cardiovascular disease require the development
      of biosignal acquisition and processing devices that are capable of supporting
      patients in their everyday life. This paper presents a Body Sensor Network (BSN)
      for use in Personal Healthcare applications. It consists of miniaturized sensor
      modules for electrocardiogram (ECG), photoplethysmogram (PPG) and
      phonocardiography (PCG) which are wirelessly connected with a coordinator to
      collect the data. Each sensor module is combined with a tri-axis accelerometer
      for patient's posture and activity measurement. As it is possible to extract
      further information about the health state by fusioning data of different
      biosensors, the wireless link based on IEEE 802.15.4 was extended by a
      synchronisation mechanism enabling synchronous sampling of the individual
      sensors. An adaptive application of algorithms for signal pre-processing and
      analysis allows the reduction of the transferred data.

PMID- 19163445
TI  - A wireless personal wearable network system to understand the biomechanics of
      orthotic for the treatment of scoliosis.
AB  - The wear tightness of an orthosis for the treatment of scoliosis varies greatly
      during daily activities. Currently, there is no commercially available product
      that can monitor force distribution inside the brace and the time that the
      othosis is worn during daily activities. Subjective feeling is the most commonly
      used method. To provide an objective measure, a battery-powered wireless personal
      wearable network system is developed. This system consists of up to 16 wireless
      force loggers and a USB ZigBee dongle. Each logger contains a force sensor and a
      wireless unit. The whole system records how much time the orthosis has been used
      and how loads distribute inside the orthoses. Laboratory tests have been
      performed; the maximum force measurement error is +/-0.02N and the resolution is
      0.1N. The average power consumption of the system is 0.3mW/h and thus a single
      AAA-sized alkaline battery is able to support the power for 6 months.

PMID- 19163446
TI  - Evaluation of obstetric gestures: an approach based on the curvature of
      quaternions.
AB  - This paper presents a method to evaluate a gesture carried out by a resident
      obstetrician by comparing it to a gesture carried out by an expert obstetrician.
      The studied gesture is the forceps blade placement. Resident paths were recorded
      on a childbirth simulator while placing forceps blades instrumented with six
      degrees of freedom sensors. The path is characterized by the positions and the
      orientations. In this paper we particularly focus on the orientations. Forceps
      orientations are expressed in the quaternion unit space and the curvature of
      quaternion path is compared by correlation to a reference defined by an expert.
      Residents have been trained on a simulator and their gestures are evaluated by
      comparing their orientation path curvatures to reference path curvatures.
      Quantitative results confirm the qualitative analysis, residents become more
      similar to the reference while training on simulator.

PMID- 19163447
TI  - Application of Raman scattering to the measurement of ligament tension.
AB  - More marginal results and complications occur as a result of knee ligament
      surgery than of other common surgical procedure. Long-term success rates of
      anterior cruciate ligament reconstruction range between 75 and 90%. The goal of
      knee surgery is to restore the normal kinematics of the knee. If the tension is
      too high, the range of motion of the joint is restricted, resulting in abnormal
      stresses on the articular cartilage and the meniscuses, and interfering with the
      revascularization of the graft. The use of Raman spectroscopy for the measurement
      of tension in ligaments and tendons is described. Measurements of the Raman
      spectrum demonstrate that the Raman frequencies shift with applied tension.

PMID- 19163448
TI  - A hybrid ultrasonic motor and electrorheological fluid clutch actuator for force
      feedback in MRI/fMRI.
AB  - This paper presents a safe, electrically powered MR-compatible actuator with a
      large range of output impedance, which can be used at the entry of the scanner
      bore. This actuator is composed of an ultrasonic motor (USM) and a torque
      controlled electrorheological fluid clutch which modulates the output torque of
      the USM. This paper describes the developments on the electrorheological fluid
      (ERF) clutch and its high voltage driver. The performances of the ERF brake
      constituting the clutch are evaluated, and its torque range is adapted using an
      epicyclic differential. The transmissible torque of the ERF clutch, i.e., the
      maximum system output torque, is 94.4 mNm and its drag torque is 2.6 mNm. The MR
      compatibility of the complete hybrid actuator is shown in extensive tests
      including subtraction of images and comparison of signal-to-noise ratios in
      powered and unpowered conditions. This novel MR-compatible actuator may be used
      to study the neural control of the hand.

PMID- 19163449
TI  - A new approach of multi-d.o.f. prosthetic control.
AB  - In this paper we propose a new method to enhance prosthetics functionality, that
      integrates concepts extracted from the neuroscience background with the
      technology mainly exploited in prosthetic control. This new method allows
      controlling multi-degrees of freedom (d.o.f.) prostheses with signals having few
      d.o.f.

PMID- 19163450
TI  - Development of new passive exercise equipment inducing contraction of functional
      muscles around knee joint without pain.
AB  - A new type of 'Passive Exercise Equipment' has been developed, which can induce
      muscular contraction of the functional muscles around knee joint. Not only user s
      who are not eager to exercise but also patients with both type 2 diabetes and
      knee joint osteoarthritis can perform exercise just by following our equipment's
      motion while sitting on it. In order to reduce knee joint pain, the equipment has
      three types of original functions. Our experiments, using the equipment, shows
      that (1) from a subjective evaluation by persons with knee joint osteoarthritis,
      knee joint pain was smaller than that of walking on a flat surface area, (2)
      glucose uptake was significantly enhanced from the Euglycemic Clamp study for
      both young healthy persons and elder persons with type 2 diabetes, and (3) 12
      weeks training using the equipment has improved the rating of the knee joint
      osteoarthritis.

PMID- 19163451
TI  - Prototype design of a wearable metal hydride actuator using a soft bellows for
      motor rehabilitation.
AB  - A bedside and home rehabilitation system for people with motor disabilities due
      to stroke or the aging process requires a human-compatible actuator with
      softness, low noise and a high power-to-weight ratio. To achieve these types of
      joint motor rehabilitation systems, we designed a wearable metal hydride (MH)
      actuator using a soft bellows. The purpose of the current study is the
      development the soft and light bellows made of a polymer laminate film for the MH
      actuator. As a result of experimental tests, this soft bellows weighs 20 times
      less and stretches 30 times longer than the metal bellows used in a conventional
      MH actuator, and it has hydrogen impermeability, flex durability and adequate
      compliance for human joints. The MH actuator using the soft bellows can drive at
      a slow and safe enough speed for motor rehabilitation of patients' limbs. These
      preliminary findings support the efficacy of an MH actuator with a soft bellows
      for the purpose of developing a system for motor rehabilitation or human power
      assist.

PMID- 19163452
TI  - Towards control of dexterous hand manipulations using a silicon Pattern
      Generator.
AB  - This work demonstrates how an in silico Pattern Generator (PG) can be used as a
      low power control system for rhythmic hand movements in an upper-limb prosthesis.
      Neural spike patterns, which encode rotation of a cylindrical object, were
      implemented in a custom Very Large Scale Integration chip. PG control was tested
      by using the decoded control signals to actuate the fingers of a virtual
      prosthetic arm. This system provides a framework for prototyping and controlling
      dexterous hand manipulation tasks in a compact and efficient solution.

PMID- 19163453
TI  - A remotely powered and wirelessly controlled intraoral electrolarynx.
AB  - Electrolarynx devices have restored the voice of many who would otherwise be
      unable to speak. Current intraoral electrolarynx devices either have unappealing
      transoral tubes or are too large to easily fit in the mouth. We introduce a
      novel, remotely powered and wirelessly controlled intraoral electrolarynx that
      addresses these issues. Due to its size, the intraoral part of the device is
      easily embedded into a maxillary denture or a dental appliance. Characteristics
      of the device, including operating distance, positional sensitivity and
      orientation sensitivity were investigated. The results show that the device can
      be remotely powered and wirelessly controlled for use as an intraoral
      electrolarynx. Speech intelligibility of the device is not presented, but will be
      in future studies.

PMID- 19163454
TI  - Advanced obstacle avoidance for a laser based wheelchair using optimised Bayesian
      neural networks.
AB  - In this paper we present an advanced method of obstacle avoidance for a laser
      based intelligent wheelchair using optimized Bayesian neural networks. Three
      neural networks are designed for three separate sub-tasks: passing through a door
      way, corridor and wall following and general obstacle avoidance. The accurate
      usable accessible space is determined by including the actual wheelchair
      dimensions in a real-time map used as inputs to each networks. Data acquisitions
      are performed separately to collect the patterns required for specified sub
      tasks. Bayesian frame work is used to determine the optimal neural network
      structure in each case. Then these networks are trained under the supervision of
      Bayesian rule. Experiment results showed that compare to the VFH algorithm our
      neural networks navigated a smoother path following a near optimum trajectory.

PMID- 19163455
TI  - RUPERT closed loop control design.
AB  - Rehabilitation robotics is an active area of research in the field of stroke
      rehabilitation. There is significant potential for improving the current physical
      rehabilitation methods after stroke through the use of robotic devices. RUPERT is
      a wearable robotic exoskeleton powered by pneumatic muscle actuators. An adaptive
      robot control strategy combining a PID-based feedback controller and an Iterative
      Learning Controller (ILC) is proposed for performing passive reaching tasks.
      Additionally, a fuzzy rule-base for estimating the learning rate for the ILC is
      also proposed. The proposed control scheme has the ability to adapt to different
      subject for performing different reaching tasks. The preliminary results from two
      able-bodied subjects demonstrate that the proposed controller can provide
      consistent performance for different subjects performing different reaching
      tasks.

PMID- 19163456
TI  - Neuro-sliding mode multivariable control of a powered wheelchair.
AB  - This paper proposes a neuro-sliding mode multivariable control approach for the
      control of a powered wheelchair system. In the first stage, a systematic
      decoupling technique is applied to the wheelchair system in order to reduce the
      multivariable control problem into two independent scalar control problems. Then
      two Neuro-Sliding Mode Controllers (NSMCs) are designed for these independent
      subsystems to guarantee system robustness under model uncertainties and unknown
      external disturbances. Both off-line and on-line trainings are involved in the
      second stage. Real-time experimental results confirm that robust performance for
      this multivariable wheelchair control system under model uncertainties and
      unknown external disturbances can indeed be achieved.

PMID- 19163457
TI  - Recovery of hand function in virtual reality: Training hemiparetic hand and arm
      together or separately.
AB  - This study describes a novel robotic system using haptic effects and objects, in
      rich, three- dimensional virtual environments (VEs) for the sensorimotor training
      of the hemiparetic hand. This system is used to compare effectiveness of two
      training paradigms, one using activities that train the hand and arm together
      (HAT) as a functional unit to training the hand and arm in similar conditions,
      separately (HAS). Four subjects practiced three hours/day for 8 days using (HAS)
      robotic simulations. Four subjects practiced same amount of time using HAT
      simulations. HAT group improved 23% in the Wolf Motor Function Test and 29% in
      the Jebsen Test of Hand Function, whereas HAS group only improved 14% and 8%. HAT
      group also demonstrated larger decreases in hand trajectory length in the VE
      based training that involved reaching and object placing, indicating improved
      limb segment coordination, (40% HAT; 19% HAS). Both groups improved the
      smoothness of robotically measured hand trajectories 56%, suggesting improved
      motor control. During virtual piano training, subjects showed similar
      improvements in key press accuracy (17% HAT; 20% HAS) however, the HAT group
      demonstrated larger improvements in average time needed to press a key (151% HAT;
      60% HAS). Our initial findings suggest that training the arm and hand as a unit
      following stroke may be more effective for improving upper extremity function
      than training the hand and arm in isolation.

PMID- 19163458
TI  - Detection of obstructive sleep apnea in children using decreases in the amplitude
      fluctuations of PPG signal and HRV.
AB  - An analysis of the HRV during decreases in the amplitude fluctuations of PPG
      (DAP) events, and their utility in OSAS screening is presented. The overall data
      set used in the study includes the polysomnographic records of 21 children. DAP
      events were automatically detected by an algorithm based on the envelope
      attenuations of the PPG. DAP events were classified as apneic or non apneic by a
      linear discriminant analysis. The features used by the linear discriminant come
      from the temporal and spectral parameters of the heart rate obtained by Smooth
      Pseudo Wigner Ville Distribution. Two indexes were defined: the number of DAP
      events per hour ratio r(DAP) and the number of apneic DAP events per hour ratio
      r(DAP)(alpha). Results show a 12% increase in accuracy for r(DAP)(alpha) with
      respect to r(DAP) in classifying 1 hour polysomnographic segments, reaching
      values of 72.7% and 80% for sensitivity and specificity, respectively. As for
      subject classification, the improvement in accuracy is 6.7% obtaining values of
      87.5% and 71.4% for sensitivity and specificity respectively. These results
      suggest that the combination of DAP and HRV could be an alternative for sleep
      apnea screening with the added benefit of low cost and simplicity.

PMID- 19163459
TI  - Examination of non-restrictive and non-invasive sleep evaluation technique for
      children using difference images.
AB  - In recent years, the inappropriate sleep style for children has become known as
      one of the important causes of behavioral disorders, for example inattentiveness
      during waking hours or hyperactivity. Consequently, screening for the children
      having sleep disorders is needed to treat in the early stage of the behavioral
      disorders. From the point of view of evaluation for children's sleep, there are
      three problems. First, the conventional polysomnogram (PSG) requires great
      investment in facility and high personnel cost so that hospitals equipped with
      the PSG examination are rare. Next, the sleep-check examination system such as
      PSG and so on requires many sensors to be attached to the client's face and body.
      So the client feels suffering severe stress and the wires of sensors trigger some
      accidents. At last, it is very difficult to get ordinary sleep style in the sleep
      examination room because of above factors. It is strongly desirable to develop a
      new method of sleep evaluation system in place of conventional PSG that is non
      restrictive and non-contact. Taking these problems into account, we devised a
      technique with these characteristics that is completely separated from sensors.
      It determines the sleep condition from body movement information by measuring
      movements using difference processing of video image. Our study of using this
      technique on pediatric patients indicated that this non-restrictive technique
      could be effective for evaluating body movement during sleep. It was looked for a
      relationship between movements information and sleep conditions.

PMID- 19163460
TI  - Cross correlation and scatter plots of the heart rate variability and R-peak
      Envelope as features in the detection of obstructive sleep apnea.
AB  - Interbeat heart rate as measured by the RR interval (RR) and R-Peak Envelope
      (RPE) are two signals that can be extracted from an Electrocardiogram (ECG) with
      relative ease and high reliability. RR and RPE have been shown to carry markers
      for detecting sleep disordered breathing (SDB). In this pilot study, we explore
      the cross correlation of RR and RPE in normal and SDB patients. Nocturnal ECG
      from 7 normal subjects and 7 SDB patients were used to obtain RR and RPE. The
      results revealed that the cross correlation of RR and RPE signals is
      significantly different between normal subjects and SDB patients (p 2x10(-6)).
      Furthermore, a new scatter plot of RR vs. RPE was developed. Optimum features
      from the RR vs. RPE scatter plot were extracted and used as input to a multilayer
      perceptron (MLP) classifier to distinguish between normal and SDB subjects, The
      detection sensitivity, specificity and accuracy for the training data set were
      95.0%, 100.0%, and 97.5%, respectively; and for the test data were 76.6%, 93.2%,
      and 84.7%, respectively.

PMID- 19163461
TI  - Variations in the accuracy of the ECG based detection of obstructive sleep apnoea
      (OSA) for different numbers of ECG leads and categories of OSA events.
AB  - This study investigates the finding that there is a more pronounced change to ECG
      physiological predictors during apnoea events compared to hypopnoea events and
      therefore accurate detection of hypopnoea events is likely to be more challenging
      than detection of apnoea events. The relevant statistical analysis was conducted
      by generating logistic regression models from the two data sets: the first one
      containing only the apnoea events and controls and the second data set containing
      only the hypopnoea events and controls. The discriminating ability of the model
      from the apnoea data set (AUC = 0.903, CI = 0.888 - 0.920) was significantly
      superior compared to the model from the hypopnoea data set (AUC = 0.842, CI =
      0.817-0.866). The second study objective investigated whether regression models
      comprising the OSA predictors derived from the two ECG signals performed better
      than models that involved parameters of a single ECG. The optimised two signal
      ECG model (AUC = 0.878 and CI = 0.864 - 0.893) outperformed the best single ECG
      model (AUC = 0.843, CI = 0.826 - 0.860), suggesting that improved results can be
      achieved using an additional ECG lead.

PMID- 19163462
TI  - Alterations in sleep EEG activity during the hypopnoea episodes.
AB  - The Obstructive Sleep Apnoea Hypopnoea Syndrome (OSAH) means 'cessation of
      breath' during the sleep hours and the sufferers often experience related changes
      in the electrical activity of the brain and heart. The aim of this paper is to
      investigate any possible changes in the human electroencephalographic (EEG)
      activity due to hypopnoea (mild case of cessation of breath) occurrences by
      applying the non-linear and linear time series methods. The results from this one
      subject study indicated significant changes in the human EEG activity due to
      hypopnoea episodes by applying the non-linear, Lyapunov exponent method at C3 EEG
      electrode site. This non-linear method can be applied in future evaluation of
      sleep EEG transients during the OSAH episodes.

PMID- 19163463
TI  - Formant frequencies of normal breath sounds of snorers may indicate the risk of
      Obstructive Sleep Apnea Syndrome.
AB  - Several differences between the airway of normal subjects and those with OSAS are
      well known. The characteristics of the upper airway may be indirectly studied
      through the formant frequencies of breathing sounds. In this work we analyze the
      formants of inspiration and exhalation sounds in snoring subjects with and
      without OSAS. Formant frequencies of inspiration and exhalation appear in the
      same bands as snores. Formant F1 is significantly lower in inspiration episodes
      of OSAS patients (p=0.008) with a decreasing tendency as the AHI increases (r=
      0.705). In addition, this formant has a significantly higher variability SF1 in
      pathological subjects, for both inspiration (p=0.022) and exhalation (p=0.038)
      episodes, as was previously found in snores. A higher variability of formant
      frequencies seems to be an indicator of the presence of OSAS. The proposed
      technique could allow the identification of OSAS patients from normal breathing
      alone.

PMID- 19163464
TI  - Parametric and nonparametric methods to generate time-varying surrogate data.
AB  - We present both nonparametric and parametric approaches to generating time
      varying surrogate data. Nonparametric and parametric approaches are based on the
      use of the short-time Fourier transform and a time-varying autoregressive model,
      respectively. Time-varying surrogate data (TVSD) can be used to determine the
      statistical significance of the linear and nonlinear coherence function
      estimates. Two advantages of the TVSD are that it keeps one from having to make
      an arbitrary decision about the significance of the coherence value, and it
      properly takes into account statistical significance levels, which may change
      with time. Our simulation examples and experimental results on blood pressure and
      heart rate data demonstrate the efficacy and applicability of the proposed TVSD
      methods.

PMID- 19163465
TI  - Transmission of brain activity in cognitive and motor tasks.
AB  - The Short-time Directed Transfer Function was used for estimation of dynamical
      patterns of brain activity propagation. The SDTF is based on the multivariate
      autoregressive model, where all channels of the process are considered
      simultaneously. Time-frequency patterns of EEG propagation were found for the
      task of finger movement and its imagination and for the Continuous Attention
      Test. The results supported the neurophysiological hypotheses concerning
      information processing in brain and in particular the theory of active
      inhibition.

PMID- 19163466
TI  - Estimation of time-varying causal connectivity on EEG signals with the use of
      adaptive autoregressive parameters.
AB  - In this paper, we address the problem of time-varying causal connectivity
      estimators on Electro-encephalographic (EEG) signals by means of Directed
      Transfer Function (DTF). The DTF method reveals causal information flows between
      brain areas, while direct DTF (dDTF) is able to distinguish and estimate only
      direct flows. Since neuro-physiological signals such as EEG and event related
      potentials (ERP) can be nonstationary, their temporal dynamics cannot be
      satisfactorily represented. Time-varying dDTF can be estimated using Kalman
      Filter for adaptive calculation of multivariate autoregressive coefficients. This
      approach can reveal transient causal relations and model time-dependent flow
      patterns. This approach was applied to simulated signals and the results
      indicated that time-varying dDTF can provide efficient estimates of connectivity
      patterns.

PMID- 19163467
TI  - A multiple coherence-based detector for evoked responses in the EEG during
      sensory stimulation.
AB  - The sampling distribution of the multiple coherence estimate between a periodic
      signal and a set of filtered versions of evoked responses embedded in additive
      noise signals is derived for the zero-coherence case. For a fixed number of
      signals used in the estimation, the probability density function varies with the
      number of data segments. Analytical expressions for both bias and variance of the
      estimate were derived and together with the critical values constitute the
      statistical apparatus for the detector based on this multiple coherence estimate.
      An illustration of the technique as applied to detect evoked responses in the
      Electroencephalogram during sensory stimulation is also provided.

PMID- 19163468
TI  - A technique to predict the time-of-arrival of a tumor response corrupted by
      clutter.
AB  - Radar-based microwave imaging has been proposed as a complementary modality for
      early stage breast cancer screening. A considerable challenge for the successful
      implementation of this technique is the reduction of clutter, or components of
      the signal originating from objects other than the tumor. To remedy problems that
      arise due to the breast shape, size and tissue variations, a novel technique is
      presented that identifies and localizes the source of a target response. The
      ability of the algorithm to predict the time-of-arrival of a tumor response in a
      signal corrupted by clutter is demonstrated.

PMID- 19163469
TI  - PCA-SGA implementation in classification and disease specific feature extraction
      of the brain MRS signals.
AB  - The medical diagnostic systems often suffer from the high dimensional data. In
      this study, Principle Component Analysis (PCA) has been used for dimensionality
      reduction of the brain Magnetic Resonance Spectroscopy (MRS) signals. Afterwards,
      the Simple Genetic Algorithms (SGA) is utilized in order to classify different
      brain diseases. SGA is later used to extract MRS signal features in case of
      metabolic brain diseases (MD). The PCA-SGA implementation received the
      specificity of 89.91%. The SGA was able to achieve the sensitivity of 84.84% and
      positive predictivity of 88.46% in extracting disease specific MRS signal
      features.

PMID- 19163470
TI  - An enhanced segmentation of blood vessels in retinal images using contourlet.
AB  - Retinal images acquired using a fundus camera often contain low grey, low level
      contrast and are of low dynamic range. This may seriously affect the automatic
      segmentation stage and subsequent results; hence, it is necessary to carry-out
      preprocessing to improve image contrast results before segmentation. Here we
      present a new multi-scale method for retinal image contrast enhancement using
      Contourlet transform. In this paper, a combination of feature extraction approach
      which utilizes Local Binary Pattern (LBP), morphological method and spatial image
      processing is proposed for segmenting the retinal blood vessels in optic fundus
      images. Furthermore, performance of Adaptive Neuro-Fuzzy Inference System (ANFIS)
      and Multilayer Perceptron (MLP) is investigated in the classification section.
      The performance of the proposed algorithm is tested on the publicly available
      DRIVE database. The results are numerically assessed for different proposed
      algorithms.

PMID- 19163471
TI  - Elliptical local vessel density: a fast and robust quality metric for retinal
      images.
AB  - A great effort of the research community is geared towards the creation of an
      automatic screening system able to promptly detect diabetic retinopathy with the
      use of fundus cameras. In addition, there are some documented approaches for
      automatically judging the image quality. We propose a new set of features
      independent of field of view or resolution to describe the morphology of the
      patient's vessels. Our initial results suggest that these features can be used to
      estimate the image quality in a time one order of magnitude shorter than previous
      techniques.

PMID- 19163472
TI  - Automated localization of the optic disc and the fovea.
AB  - The detection of the position of the normal anatomy in color fundus photographs
      is an important step in the automated analysis of retinal images. An automatic
      system for the detection of the position of the optic disc and the fovea is
      presented. The method integrates the use of local vessel geometry and image
      intensity features to find the correct positions in the image. A kNN regressor is
      used to accomplish the integration. Evaluation was performed on a set of 250
      digital color fundus photographs and the detection performance for the optic disc
      and the fovea were 99.2% and 96.4% respectively.

PMID- 19163473
TI  - Robust optic disc location via combination of weak detectors.
AB  - This paper presents a new robust approach for the automatic location of the optic
      disc. We detect several candidates independently for optic disc, macula and the
      main blood vessels (arcades). Candidates are sorted by reliability. The space of
      all possible triplets disc-macula-arcades is searched using a-priori anatomical
      knowledge, selecting the triplet formed by the most reliable candidates
      satisfying anatomical constraints best. This triplet includes the best optic disc
      location. The approach was tested using the well-known STARE data set (81 images:
      31 healthy retinas and 50 containing pathological lesions of various types and
      severity) and 20 wide-field-of-view scanning laser ophthalmoscope (SLO) images
      acquired with an OPTOS instrument. We achieved 91.4% detection rate in the STARE
      data set and 100% in the OPTOS data set.

PMID- 19163474
TI  - Detection of the optic disc in images of the retina using the Hough transform.
AB  - We propose a method to locate automatically the optic disc (OD) in fundus images
      of the retina. Based on the properties of the OD, our proposed method includes
      edge detection using the Sobel or the Canny method, and detection of circles
      using the Hough transform. The Hough transform assists in the detection of the
      center and radius of a circle that approximates the margin of the OD. Based on
      the feature that the OD is one of the bright areas in a fundus image, potential
      circles detected by the Hough transform are analyzed using intensity. Forty
      images of the retina from the DRIVE database were used to evaluate the
      performance of the proposed method. The success rates including both good and
      acceptable detections were 92.50% using the Sobel operators and 80% using the
      Canny edge detector.

PMID- 19163475
TI  - An improved system for the automatic estimation of the Arteriolar-to-Venular
      diameter Ratio (AVR) in retinal images.
AB  - The Arteriolar-to-Venular diameter Ratio (AVR), a parameter derived from vessel
      caliber measurements in a specific region of retinal images, is used as a
      descriptor of generalized arteriolar narrowing, an eye fundus sign often seen in
      patients affected by hypertensive or diabetic retinopathies. We developed an
      improved system to compute AVR in a totally automatic way. Images are at first
      enhanced to highlight the vessel network, which is then traced by a vessel
      tracking algorithm. From the detected vessel structure, the position of the optic
      disc is derived and the region inside which the AVR data are to be measured is
      determined. Vessels within this region are classified as either arteries or
      veins, their caliber is estimated and the AVR parameter is eventually computed.
      Improvements with respect to the previous version are related to post-processing
      algorithms to enhance vessel tracking and a totally new artery/vein
      discrimination technique. Results provided by the new system have been compared
      with manually derived AVR values on 20 eye fundus images, resulting in a final
      correlation coefficient of 0.88.

PMID- 19163476
TI  - Selection of spectro-temporal patterns in multichannel MEG with support vector
      machines for schizophrenia classification.
AB  - We present a new framework for the diagnosis of schizophrenia based on the
      spectro-temporal patterns selected by a support vector machine from multichannel
      magnetoencephalogram (MEG) recordings in a verbal working memory task. In the
      experimental paradigm, five letters appearing sequentially on a screen were
      memorized by subjects. The letters constituted a word in one condition and a
      pronounceable nonword in the other. Power changes were extracted as features in
      frequency subbands of 248 channel MEG data to form a rich feature dictionary. A
      support vector machine has been used to select a small subset of features with
      recursive feature elimination technique (SVM-RFE) and the reduced subset was used
      for classification. We note that the discrimination between patients and controls
      in the word condition was higher than in the non-word condition (91.8% vs 83.8%).
      Furthermore, in the word condition, the most discriminant patterns were extracted
      in delta (1-4 Hz), theta (4-8Hz) and alpha (12-16 Hz) frequency bands. We note
      that these features were located around the left frontal, left temporal and
      occipital areas, respectively. Our results indicate that the proposed approach
      can quantify discriminative neural patterns associated to a functional task in
      spatial, spectral and temporal domain. Moreover these features provide
      interpretable information to the medical expert about physiological basis of the
      illness and can be effectively used as a biometric marker to recognize
      schizophrenia in clinical practice.

PMID- 19163477
TI  - Altered multijoint reflex coordination is indicative of motor impairment level
      following stroke.
AB  - Following stroke, individuals often are unable to activate their elbow and
      shoulder muscles independently. There is growing evidence that altered reflex
      pathways may contribute to these abnormal patterns of activation or muscle
      synergies. Most studies investigating reflex function following stroke have
      examined only individual joints at rest. Thus, the purpose of this study was to
      quantify multijoint reflex contributions to the stereotyped muscle synergies
      commonly observed following stroke. We hypothesized that the patterns of reflex
      coordination mirror the abnormal muscle coactivity patterns previously reported
      for voluntary activation. 10 chronic stroke and 8 age-matched control subjects
      participated. Reflexes were elicited by perturbing the arm with a 3 degree of
      freedom robot while subjects exerted voluntary forces at the elbow and shoulder.
      The force conditions tested were selected to assess the influence of gravity and
      the influence of joint torque generation without gravity on reflex coordination.
      Reflex magnitude was quantified by the average rectified electromyogram, recorded
      from 8 muscles that span the elbow and shoulder. Patterns of reflex coordination
      were quantified using independent components analysis. Results show significant
      reflex coupling between elbow flexor and shoulder abductor-extensor muscles in
      stroke patients during isolated elbow and shoulder torque generation and during
      active arm support against gravity. Identified patterns of stretch reflex
      coordination were consistent with the stereotyped voluntary flexion synergy,
      suggesting reflex pathways contribute to abnormal muscle coordination following
      stroke.

PMID- 19163478
TI  - Abnormal EMG-force slope estimates in the first dorsal interosseous of
      hemiparetic stroke survivors.
AB  - Hemispheric brain injury resulting from a stroke is often accompanied by weakness
      in contralateral limbs. Appropriate motoneuronal recruitment and rate modulation
      is necessary to optimize muscle force production utilizing residual neuromuscular
      elements. We sought to determine whether weakness in a hand muscle in stroke
      survivors is partially attributable to alterations in the control of the motor
      units in the affected muscles. Specifically, our goal was to characterize whether
      surface EMG amplitude, a gauge of neural input, was systematically larger as a
      function of force, in paretic muscles when compared to the contralateral muscles
      in the same subject, and to neurologically intact subjects. We tested the first
      dorsal interosseous (FDI) in five hemiparetic and six neurologically intact
      subjects. In four of the stroke subjects the EMG-force slope was significantly
      greater on the affected side as compared to the contralateral side as well as
      compared to neurologically intact subjects. We discuss possible experimental as
      well as physiological factors that may contribute to an increased slope,
      concluding that a combination of abnormal firing rate patterns and changes in MU
      control are the most likely reasons for the observed changes.

PMID- 19163479
TI  - A Handheld Electrical Impedance Myography probe for the assessment of
      neuromuscular disease.
AB  - Electrical Impedance Myography (EIM) is a non-invasive, painless clinical
      technique for the diagnosis and monitoring of a variety of neuromuscular diseases
      including amyotrophic lateral sclerosis and focal nerve injuries. It involves the
      application of a low-intensity alternating current to a muscle group and the
      measurement of the consequent surface voltage patterns. This paper presents a
      system for the rapid and accurate acquisition of data employing an interrogating
      signal composed of multiple tones with frequencies between 10 kHz and 4 MHz. The
      use of this composite signal makes possible measurement of impedance at multiple
      frequencies simultaneously. In addition, this system takes impedance measurements
      at multiple orientations with respect to the muscle fibers by means of an
      electronically reconfigurable electrode array and utilizes the linearity of
      muscle tissue to reduce the required measurement time. Testing of the EIM system
      on beef has established the capability of this system to rapidly detect the
      anisotropic conductive properties of muscle tissue at multiple frequencies.

PMID- 19163480
TI  - A new approach to predicting postconcussion syndrome after mild traumatic brain
      injury based upon eye movement function.
AB  - Following on from our earlier findings of a close relationship between motor
      function and outcome after mild traumatic brain injury (mTBI), this study
      examined whether it might be possible to predict poor recovery in the form of
      postconcussion syndrome (PCS) based upon early eye and arm motor function. Within
      1 week post-injury, we assessed 37 mTBI patients on measures of saccades,
      oculomotor smooth pursuit, upper-limb visuomotor function, neuropsychological
      status, and self-reported health condition. At 3 months, 8 patients met the
      criteria for PCS. Using discriminant function analyses, we examined whether this
      future PCS-group could be identified prospectively based on motor function,
      neuropsychological status, and self-reported health condition at 1 week post
      injury. Early eye movement function was the most effective in distinguishing
      between PCS and non-PCS patients, achieving a sensitivity and specificity of 100%
      in the present sample. This was followed by self-reported early health condition
      (sensitivity: 87%, specificity: 97%), early upper-limb motor performance (87%,
      97%), neuropsychological function (62%, 100%), and age, gender, education and
      clinical measures of trauma severity (37%, 87%). Leave-one-out validation
      analyses confirmed eye movements as the most robust discriminator (sensitivity:
      62%, specificity: 97%). Assessment of eye movement function after mTBI may
      contribute to a prospective identification of patients who develop PCS,
      supporting the targeting of early health-care intervention.

PMID- 19163481
TI  - Motion analysis in delirium: a wavelet based approach for sub classification.
AB  - The usefulness of motor subtypes of delirium is unclear due to inconsistency in
      sub-typing methods and a lack of validation with objective measures of motor
      activity levels. Patients were studied with hyperactive, hypoactive, and mixed
      presentations of delirium. The patient's activity was determined with 24 hour
      accelerometer-based monitoring and a continuous wavelet transform was applied
      with a wavelet deemed suitable to distinguish between these motor presentations.
      The procedures were well tolerated and motor presentations were readily
      distinguished using the accelerometry-based measurements.

PMID- 19163482
TI  - Non-thermal dielectric barrier discharge plasma treatment of endothelial cells.
AB  - Non-thermal dielectric barrier discharge plasma is now being widely developed for
      various medical applications such as skin sterilization, blood coagulation,
      induction of apoptosis in malignant tissues, and wound healing among others. In
      this paper, we investigate the toxicity of non-thermal plasma treatment on
      endothelial cells, which line all blood contacting surfaces in the body. Our
      initial results indicate that low power non-thermal plasma is relatively non
      toxic to endothelial cells at short exposure times up to 30 s, while non-thermal
      plasma treatment at longer exposure times is cytotoxic. Non-thermal plasma at
      shorter exposure times may induce proliferation in the cells.

PMID- 19163483
TI  - Electromagnetically enhanced coating of a sintered titanium grid with human SAOS
      2 osteoblasts and extracellular matrix.
AB  - The surface modification of a sintered titanium scaffold could play an important
      role in bone tissue engineering. In this study we have followed a biomimetic
      strategy where electromagnetically stimulated human SAOS-2 osteoblasts
      proliferated and built their extracellular matrix on a sintered titanium grid. In
      comparison with control conditions (standard cell culture incubator, where no
      electromagnetic stimulus was detectable), the electromagnetic stimulus (magnetic
      field, 2 mT; frequency, 75 Hz) increased the cell proliferation and the surface
      coating with decorin, osteopontin, and type-I collagen. The electromagnetic
      stimulus aimed at obtaining a better surface coating of the sintered titanium
      grid in terms of cell colonization and bone matrix. The superficially modified
      biomaterial could be used, in clinical applications, as an implant for bone
      repair.

PMID- 19163484
TI  - Improved oxygen diffusion and mechanical aggregation of tumor colonies in a novel
      stirred mini-bioreactor.
AB  - The feasibility of a novel stirred bioreactor, the rotating aerial disk (RAD)
      design, was tested in this study. The novelty lies in its method of medium
      recirculation by convective airflow using a non-contact planar disc, a variation
      on a physically defined theoretical model. Computational predictions of improved
      oxygenation were confirmed by increases in measured dissolved oxygen, even at
      Reynolds numbers (100-200) where flow is mostly laminar. EL-4 mouse lymphoma
      cells grown for the first time as suspension cultures in the RAD bioreactor, were
      mechanically re-organization into dense, circular three-dimensional colonies
      (diameter 3-5 mm, thickness 5-800 microm), more rapidly than we have observed
      previously. Cell proliferation in the RAD vessels was similar to static cultures,
      although lactate production from glucose was significantly lower, suggesting a
      shift toward aerobic glycolysis. This possible reversal of the 'Warburg effect'
      was accompanied by a decrease in mitochondrial activity, perhaps reflecting a
      more quiescent cytoplasmic state. The RAD device may be useful as scalable, three
      dimensional solid tumor model under more physiological conditions then static
      culture.

PMID- 19163485
TI  - Engineering of functional contractile cardiac tissues cultured in a perfusion
      system.
AB  - Overcoming the limitations of diffusional transport in conventional culture
      systems remains an open issue for successfully generating thick, compact and
      functional cardiac tissues. Previously, it was shown that perfusion systems
      enhance the yield and uniformity of cell seeding and cell survival in thick
      cardiac constructs. The aim of our study was to form highly functional cardiac
      constructs starting from spatially uniform, high density cell seeded constructs.
      Disk-shaped elastomeric poly(glycerol sebacate) scaffolds were seeded with
      neonatal rat cardiomyocytes and cultured for eight days with direct perfusion of
      culture medium or statically in a six-well plate. In the perfusion experimental
      group, the integrity of some disks was well maintained, whereas in others a
      central hole was formed, resulting in ring-shaped constructs. This allowed us to
      also study the effects of construct geometry and of interstitial flow versus
      channel perfusion. The ring-shaped constructs appeared to have a denser and more
      uniform deposition of extracellular matrix. In response to electrical
      stimulation, the fractional area change of the ring-shaped constructs was 7.3 and
      2.7 times higher than for disk-shaped tissues cultured in perfusion or
      statically, respectively. These findings suggest that a combination of many
      factors, including scaffold elasticity and geometry and the type of perfusion
      system applied, need to be considered in order to engineer a cardiac construct
      with high contractile activity.

PMID- 19163486
TI  - Design of electrical stimulation bioreactors for cardiac tissue engineering.
AB  - Electrical stimulation has been shown to improve functional assembly of
      cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were
      found in past studies to have the best current injection characteristics. The
      goal of this study was to develop rational experimental design principles for the
      electrodes and stimulation regime, in particular electrode configuration,
      electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared
      via electrochemical impedance spectroscopy (EIS) and we identified a safety range
      of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for
      neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude
      with recommendations for studies involving carbon electrodes for cardiac tissue
      engineering.

PMID- 19163487
TI  - Arterial complex elastic modulus was preserved after an intercontinental
      cryoconserved exchange.
AB  - There is a pressing need to obtain adequate vascular substitutes for arterial by
      pass or reconstruction. Since the performance of venous and commercially
      prosthetic grafts is not ideal and the availability of autologous arteries is
      limited, the use of cryopreserved arteries has emerged as a very attractive
      alternative. In this sense, the development of an inter-continental network for
      cryopreserved tissue exchange would improve international cooperation increasing
      the possibilities of obtaining the requested materials. In this work, the effects
      of an inter-continental shipment, which includes cryopreservation, on the
      biomechanical properties of sheep aortas were evaluated by means of the arterial
      complex elastic modulus. It is shown that these properties were preserved after
      the shipment. The actual possibilities of establishing a network for arterial
      exchange for the international cooperation are discussed.

PMID- 19163488
TI  - Pathways to success in biomedical engineering.
AB  - A valuable session for any student aspiring to venture into graduate biomedical
      engineering research, or alternatively into industrial or clinical service. Gain
      tips from panelists on how to successfully navigate through the issues involved
      in the bioengineering profession and how to accomplish your best.

PMID- 19163489
TI  - Tracking rhythm in long-term EEG recordings using empirical mode calculation.
AB  - A novel algorithm for the detection and tracking of rhythmic patterns in the EEG
      signal is presented. The algorithm includes the following steps: 1) linear
      filtering using symmetric impulse response, 2) calculation of the first intrinsic
      mode of the filter output and 3) calculation of instantaneous frequency and
      amplitude using the Hilbert transform. The linear filter is adapted according to
      the instantaneous frequency. The algorithm is shown to perform well in tracking
      the alpha rhythm (the alpha coma pattern) in critically ill patients sedated with
      midazolam.

PMID- 19163490
TI  - Automatic screening of Obstructive Sleep Apnea from the ECG based on Empirical
      Mode Decomposition and wavelet analysis.
AB  - This study proposes three different methods to evaluate Obstructive Sleep Apnea
      (OSA) during sleep time solely based on the ECG signal. OSA is a common sleep
      disorder produced by repetitive occlusions of the upper airways, which produces a
      characteristic pattern on the ECG. Extraction of ECG characteristics as the heart
      rate variability and the QRS peak area offer alternative measures for cheap, non
      invasive and reliable pre-diagnosis of sleep apnea. 50 of the 70 recordings from
      the database of the Computers in Cardiology Challenge 2000, freely available on
      Physionet, have been used in this analysis, subdivided in a training and a
      testing set. We investigated the possibilities concerning the use of the recently
      proposed method Empirical Mode Decomposition in this application and compared it
      with the established Wavelet Analysis. From the results of these decompositions
      the eventual features were extracted, complemented with a series of standard HRV
      time domain measures and three extra non-linear measures. Of all features
      smoothed versions were calculated. From the obtained feature set, the best
      performing feature subset was used as the input of a Linear Discriminant
      Classifier. In this way we were able to classify the signal on a minute-by-minute
      basis as apneic or non-apneic with an accuracy of around 90% and to perfectly
      separate between apneic and normal patients, using around 20 to 40 features and
      with the possibility to do this in three alternative ways.

PMID- 19163491
TI  - Quantification of combined method for interferences reduction in multichannel
      surface electroenterogram.
AB  - Surface electroenterogram (EEnG) is a non-invasive method for monitoring the
      intestinal motility. However, surface EEnG signals are contaminated by strong
      physiological interferences. The main interferences which affect high-frequency
      components of surface EEnG are cardiac activity and movement artifacts. The aim
      of this work is to quantify the effectiveness of a combined method based on
      empirical mode decomposition and independent component analysis to remove these
      interferences from multichannel surface EEnG. In order to do so, several
      parameters were calculated from five recording sessions: Signal-to-ECG
      interference ratio (S/I) and variation of energy over 2 Hz (EF2). The results
      show that the S/I of processed signals was significantly higher than that of
      original signals, moreover the improvement of the S/I ratio is due to the
      attenuation of energy associated to interference. The proposed method also allows
      cancelling movement artifacts from surface EEnG, reducing considerably the non
      physiological variation of EF2. Furthermore after the application of the combined
      method, correlation coefficient between EF2 of internal recording with EF2 of
      surface recording is greatly higher. Therefore, the proposed method could be
      helpful to reduce high-frequency interferences in EEnG recording and to provide
      more robust non-invasive intestinal motility indicators.

PMID- 19163492
TI  - Time-Frequency Representations for second heart sound analysis.
AB  - Several researches have tried to provide a means to analyze the second heart
      sound (S2) in an attempt to understand the functional mechanisms in its genesis
      and for diagnosis purposes. In this work we tested Time-Frequency Representation
      (TFR) for simulated S2 selecting and applying classical and modern TFRs such as
      the Spectrogram, the Wigner-Ville Distribution, the Time Varying Autoregressive
      (TVAR) model, the Scalogram, and the Hilbert-Huang Spectrum (HHS) by Empirical
      Mode Decomposition. Two performance measures are proposed, the first one based on
      local 2D correlations (rho) between the ideal and the estimated TFRs images,
      while the second one based on time moments of the TFR images to provide the
      normalized root-mean-square error (NRMSE). Under no noise conditions, the TFRs by
      HHS and the TVAR modeling, by the Burg algorithm, resulted in a rho(average) of
      0.788 and 0.812, and NRMSE of 0.172 and 0.195, respectively. Therefore, based on
      the lowest NRMSE, HHS was considered the TFR with the best performance.
      Afterward, HHS was applied to real S2 acquired at the aortic and pulmonary focal
      points.

PMID- 19163493
TI  - Analysis of discontinuous adventitious lung sounds by Hilbert-Huang spectrum.
AB  - It is now widely accepted that crackles are associated with different pulmonary
      pathologies and different efforts have been done to detect and to extract them.
      Consequently, due to the difficulty for their characterization, the selection of
      an adequate time-frequency representation (TFR) for the analysis of their time
      frequency dynamics is important. Traditionally, normal and abnormal lung sounds
      have been analyzed by the Spectrogram (SP). However, this analysis tool has
      certain disadvantages when one deals with nonstationary signals. As an effort to
      point out the appropriate analysis tool for crackles, this paper shows the
      performance of the Hilbert-Huang spectrum (HHS) for the analysis of fine and
      coarse crackles, simulated and real ones. The HHS allowed to analyze the evolving
      time-frequency of crackle sounds straightforward with good resolution compared
      with SP. Beside this enhanced time-frequency course, HHS could be useful to
      establish a signature to detect and separate fine from coarse crackles in order
      to screen pathologies and their progress during medication.

PMID- 19163494
TI  - Empirical mode decomposition applied to tissue artifact removal from respiratory
      signal.
AB  - Estimation of respiration commonly employs piezoelectric sensors secured to rib
      cage and abdominal belts. However, these respiratory signals are often
      contaminated by tissue artifact. This paper presents a signal decomposition
      technique for tissue artifact removal in respiratory signals, based on empirical
      mode decomposition (EMD). After introducing the theoretical foundation, this
      method is performed on three synthetic signals, and performance of tissue
      artifact removal using EMD is compared with low-pass filter and independent
      component analysis (ICA) techniques. A simulation study and experimental results
      show that EMD can effectively remove tissue artifact in respiratory signals.

PMID- 19163495
TI  - A survey of power efficient technologies for Wireless Body Area Networks.
AB  - Wireless Body Area Networks (WBANs) of intelligent sensors emerged as the most
      promising architecture for ambulatory health monitoring. Integrated in an m
      Health system they provide means for unobotrusive ubiquitous monitoring. However,
      proper design of wireless communication system is application dependent and
      critically influences system performance and user acceptance. In this paper we
      present a survey of existing and emerging wireless communication technologies and
      critical parameters for the system design.

PMID- 19163496
TI  - Advances in textile sensing and actuation for e-textile applications.
AB  - SMART fabrics and interactive textiles (SFIT) are conceived as innovative textile
      structure integrating sensing, actuation, electronic, and power and/or
      communication functions. Due to their multifunctional interactivity, enabled by
      wearable devices that are flexible and conformable to the human body, e-textiles
      are considered relevant promoters of a higher quality of life and progress in
      biomedicine, as well as in several health-focused disciplines, such as
      biomonitoring, rehabilitation, telemedicine, teleassistance, ergonomics and sport
      medicine.

PMID- 19163497
TI  - Inverse computational feedback optimization imaging applied to time varying
      changes in a homogeneous structure.
AB  - The technique of inverse computational feedback optimization imaging allows for
      the imaging of varying tissue without the continuous need of a complex imaging
      systems such as an MRI or CT. Our method trades complex imaging equipment for
      computing power. The objective is to use a baseline scan from an imaging system
      along with finite element method computational software to calculate the
      physically measurable parameters (such as voltage or temperature). As the
      physically measurable parameters change the computational model is iteratively
      run until it matches the measured values. Optimization routines are implemented
      to accelerate the process of finding the new values. Presented is a computational
      model demonstrating how the inverse imaging technique would work with a simple
      homogeneous sample with a circular structure. It demonstrates the ability to
      locate an object with only a few point measurements. The presented computational
      model uses swarm optimization techniques to help find the object location from
      the measured data (which in this case is voltage).

PMID- 19163498
TI  - Deformable registration for intra-operative cone-beam CT guidance of head and
      neck surgery.
AB  - The computational and geometric performance of Demons deformable registration
      techniques were investigated in the application of cone-beam CT (CBCT) for intra
      operative guidance of head and neck surgery. A prototype C-arm providing CBCT
      images of sub-mm spatial resolution and soft-tissue contrast was used to acquire
      images of a cadaveric head before and after surgical intervention. Four
      deformable registration methods were investigated both in terms of their
      convergence behavior (time and number of iterations required) and registration
      accuracy (correlation between deformed and target images and the corresponding
      target registration error, TRE). Rigid registration alone exhibited a TRE of (2.6
      +/- 1.0) mm, compared to a TRE of (0.8 +/- 0.3) mm obtained with deformable
      registration. A fast symmetric demons implementation was identified as the most
      suitable for intra-operative use in terms of speed, image quality, and accuracy.
      Increasing the spatial resolution of CBCT images was found to increase
      registration accuracy at the cost of computational expense. Intra-operative CBCT
      combined with deformable registration offers to overcome conventional limitations
      of guidance by preoperative images alone and presents an accurate method of
      integrating imaging and planning data in a manner that properly reflects changes
      in the intra-operative state.

PMID- 19163499
TI  - Initial investigation of an automatic registration algorithm for surgical
      navigation.
AB  - The procedure required for registering a surgical navigation system prior to use
      in a surgical procedure is conventionally a time-consuming manual process that is
      prone to human errors and must be repeated as necessary through the course of a
      procedure. The conventional procedure becomes even more time consuming when intra
      operative 3D imaging such as the C-arm cone-beam CT (CBCT) is introduced, as each
      updated volume set requires a new registration. To improve the speed and accuracy
      of registering image and world reference frames in image-guided surgery, a novel
      automatic registration algorithm was developed and investigated. The surgical
      navigation system consists of either Polaris (Northern Digital Inc., Waterloo,
      ON) or MicronTracker (Claron Technology Inc., Toronto, ON) tracking camera(s),
      custom software (Cogito running on a PC), and a prototype CBCT imaging system
      based on a mobile isocentric C-arm (Siemens, Erlangen, Germany). Experiments were
      conducted to test the accuracy of automatic registration methods for both the
      MicronTracker and Polaris tracking cameras. Results indicate the automated
      registration performs as well as the manual registration procedure using either
      the Claron or Polaris camera. The average root-mean-squared (rms) observed target
      registration error (TRE) for the manual procedure was 2.58 +/- 0.42 mm and 1.76
      +/- 0.49 mm for the Polaris and MicronTracker, respectively. The mean observed
      TRE for the automatic algorithm was 2.11 +/- 0.13 and 2.03 +/- 0.3 mm for the
      Polaris and MicronTracker, respectively. Implementation and optimization of the
      automatic registration technique in Carm CBCT guidance of surgical procedures is
      underway.

PMID- 19163500
TI  - Effect of fiducial configuration on target registration error in intraoperative
      cone-beam CT guidance of head and neck surgery.
AB  - Advances in image-guided surgery have led to minimally-invasive, high-precision
      procedures that increase the efficacy of treatment, minimize surgical
      complications, and reduce patient recovery time. A recent advance in
      intraoperative 3D imaging includes cone-beam CT (CBCT) implemented on a mobile C
      arm. This paper investigates the effect of the number and configuration of
      fiducials on target registration error (TRE) and identifies fiducial
      configurations that minimize TRE for rigid point-based registration in CBCT
      guided head and neck surgery. Best configurations were those that minimized the
      distance between the centroid of fiducials and the surgical target while
      maximizing fiducial separation (distance from principal axes). Configurations
      with as few as 4 fiducials could be identified that minimized TRE (e.g., TRE <
      0.3 mm for the pituitary, cochlea, and nasion), with more fiducials (6 or more)
      providing improved TRE uniformity throughout the volume of clinical interest. If
      possible, fiducials affixed to the skin or cranium (e.g., 4-6 markers) should
      include a majority about the target (to minimize centroid-to-target distance)
      with others at a distance (to maximize separation). A greater number of fiducials
      distributed evenly can provide low, uniform TRE for all targets--e.g., 8 markers,
      TRE approximately 0.2-0.6 mm throughout the volume of interest. Such work helps
      guide the implementation of C-arm CBCT in head and neck surgery in a manner that
      maximizes surgical precision and exploits intraoperative image guidance to its
      full potential.

PMID- 19163501
TI  - Characterization and 3D correction of geometric distortion in low-field open
      magnet MRI.
AB  - In this paper, we present a method to characterize and correct geometric image
      distortion in 0.2 T MR images. A large 3D phantom with spherical balls was used
      to characterize geometric distortion on an AIRIS Mate 0.2 T MR Scanner (Hitachi).
      MR images of the phantom were acquired in axial, sagittal and coronal planes
      using 2D Fast Spin Echo (FSE) sequence and distortions were measured at each
      control point. Two piecewise interpolation methods were then applied to correct
      geometric distortion. Distortion was characterized and corrected in any axial,
      sagittal or coronal slice within an effective FOV of 330(LR) x 180(AP) x 210(HF)
      mm(3). The distortion was reduced from 16 mm to 1.2 mm at 180 mm from the magnet
      center. A fast and accurate method for correction of geometric distortion was
      performed within large distances from the magnet isocenter.

PMID- 19163502
TI  - A new lateral guidance device for stereotactic breast biopsy using an add-on unit
      to an upright mammography system.
AB  - Stereotactic breast biopsy (SBB) is the gold standard for noninvasive breast
      cancer diagnosis. Current systems rely on one of two methods for needle
      insertion: a vertical-approach (from above the breast compression plate) or a
      lateral-approach (parallel to the compression plate). While the vertical-approach
      is more commonly used, it is not feasible in patients with thin breasts (less
      than 3 cm thickness after compression) or with superficial lesions. We present a
      novel design of lateral guidance device for SBB which addresses these limitations
      of the vertical-approach, and provides improvements over existing lateral
      guidance hardware. This device incorporates spherical linkages to allow two
      degrees of rotational freedom in the needle trajectory for increased targeting
      flexibility, as well as an adjustable rigid needle support to minimize needle
      deflection within the tissue. Needle placement error in SBB experiments is
      compared using both the new lateral guidance device and a commercial lateral
      guidance device in agar phantoms. The effect of elevation angle on needle
      placement accuracy using the new lateral guidance device is also assessed.
      Finally, a biopsy accuracy experiment is presented using a certified SBB phantom
      to compare the new design and the commercial lateral guidance device. In these
      experiments, SBB performed using the new lateral guidance device resulted in
      improved needle placement error and biopsy accuracy, while increasing targeting
      flexibility and maintaining procedural workflow.

PMID- 19163503
TI  - Noninvasive thermal coagulation of deep subsurface tissue structures using a
      laser probe with integrated contact cooling.
AB  - Cooling methods are used during cosmetic laser surgery to preserve a superficial
      layer of the skin surface. This study investigates contact cooling for sparing a
      deeper layer of the tissue surface during laser irradiation of subsurface
      tissues, with the goal of developing noninvasive laser therapy applications
      beyond cosmetic surgery. A laser probe was designed and tested for simultaneous
      laser irradiation and contact cooling of liver tissue, ex vivo. Gross and
      histologic examination was used to quantify thermal lesion dimensions. Liver
      lesions of 5.8-mm-diameter were created, while preserving the tissue surface to a
      depth of 1.5 mm. In vivo animal studies are planned to optimize the laser and
      cooling parameters for potential clinical applications.

PMID- 19163504
TI  - The laser driven heating balloon catheter: vessel dilatation characteristics.
AB  - We studied on the dilatation characteristics of our new angioplasty, photo-thermo
      dynamic balloon (PTDB) angioplasty, which provides short-term heating (15s, 50-70
      degrees C) dilatation by the combination of laser heat generator and fluid
      perfusion. In this study, we employed the ex vivo experiments to demonstrate the
      feasibility of our PTDB angioplasty with extracted porcine carotid artery.
      Balloon temperature and heating duration were easily controlled with the laser
      power and irradiation duration. Arterial dilatation was performed with the
      prototype PTDB catheter (3mm in diameter) ex vivo, sufficient dilation was
      attained with low dilatation pressure (2atm) that is lower than the limit
      pressure of elastic region (8atm in this case). The principal of our PTDB
      angioplasty that was based on the experimental results was dilatation in elastic
      region, while traditional POBA was accompanied with plastic deformation of
      artery. It is predicted that successful way of PTDB dilatation was attributed to
      collagen softening. Collagen coagulation and/or restructure after the heating
      dilatation might suspend the dilated arterial lumen. We demonstrated the
      feasibility of our PTDB angioplasty. We think collagen denaturation degree may be
      the important factor in this methodology.

PMID- 19163505
TI  - Catheter-based ultrasound devices and MR thermal monitoring for conformal
      prostate thermal therapy.
AB  - Catheter-based ultrasound applicators have been developed for delivering
      hyperthermia or high-temperature thermal ablation of cancer and benign disease of
      the prostate. These devices allow for control of heating along the length and
      angular expanse during therapy delivery. Four types of transurethral applicators
      were devised for thermal treatment of prostate combined with MR thermal
      monitoring: sectored tubular transducer devices with directional heating patterns
      and rotation; planar and curvilinear devices with narrow heating patterns and
      rotation; and multi-sectored tubular devices capable of dynamic angular control
      without applicator movement. Interstitial devices (2.4 mm OD) have been developed
      for percutaneous implantation with directional or dynamic angular control. In
      vivo experiments in canine prostate under MR temperature imaging were used to
      evaluate these devices and develop treatment delivery strategies. MR thermal
      imaging was used to monitor temperature and thermal dose in multiple slices
      through the target volume. Multi-sectored transurethral applicators can
      dynamically control the angular heating profile and target large regions of the
      gland in short treatment times without applicator manipulation. The sectored
      tubular, planar, and curvilinear transurethral devices produce directional
      coagulation zones, extending 15-20 mm radial distance to the outer prostate
      capsule. Sequential rotation under motor control and modulated dwell time can be
      used to tightly conform thermal ablation to selected regions. Interstitial
      implants with directional devices can be used to effectively ablate targeted
      regions of the gland while protecting the rectum. The MR derived 52 degrees C and
      lethal thermal dose contours (t43=240 min) effectively defined the extent of
      thermal damage and provided a means for real-time control of the applicators.
      Catheter-based ultrasound devices, combined with MR thermal monitoring, can
      produce relatively fast (5-40 min) and precise thermal ablation of prostate.

PMID- 19163506
TI  - In vitro evaluation of an oscillating dual-mode ultrasound probe for sector
      imaging and directive therapy.
AB  - Interstitial probes have been shown as effective devices to deliver high
      intensity ultrasound therapy. Here, cylindrically-focused dual-mode transducers
      with either one or 5-elements were characterized, and a monoelement probe was
      evaluated in vitro. In therapy mode, the transducers were maximally efficient (>
      or =70%) at 5.6 MHz with surface intensities up to 20 W/cm(2). In imaging mode,
      fractional bandwidths were 46% and 50+/-4% (ave+/-std) for the monoelement and 5
      element transducers respectively. Axial and lateral resolutions were 0.5 mm and
      1.0 mm, respectively, for both transducers as measured with a point scatterer in
      the focal plane. After characterization, the oscillating probe was used to image
      and apply therapy to porcine liver. B-mode images over a 140 degrees sector were
      formed before and after therapy, which was applied for 90 s at each of 5 angles
      separated by 20 degrees (e.g. -40 degrees , -20 degrees, 0 degrees, 20 degrees,
      40 degrees) to form a composite lesion. Transducer surface intensity was 18
      W/cm(2). Therapy was interrupted at 125 ms intervals to collect pulse/echo data
      along the therapy axes. Data were displayed in real-time as an M-mode image to
      monitor therapy. B-mode images adequately represented the liver tissue. M-mode
      image data agreed well with the formation of lesions in the liver.

PMID- 19163507
TI  - A localization method of lesions induced by High Intensity Focused Ultrasound
      based on acoustic backscatter change.
AB  - High Intensity Focused Ultrasound (HIFU) has been investigated as a therapeutic
      modality for many medical applications. We investigated a noninvasive technique
      for the localization of HIFU-induced lesions based on the change in backscattered
      radio frequency (RF) signals. HIFU was applied to chicken breast tissue and we
      compared lesion locations obtained from RF data with our processing method, from
      the dissected tissues after exposure, and from B-mode images if exposures had
      resulted in hyperecho. RF amplitude of the focal spot was found to decrease, even
      without hyperecho in B-mode images. No significant difference was found on
      localization accuracy between the RF-based and the hyperecho-based method
      (p=0.76). In cases without hyperecho, the distance between RF-based locations and
      measured physical lesion locations was 3.37 +/- 1.59 mm. The axial and lateral
      difference was 2.00 +/- 2.31 mm and 0.85 +/- 2.15 mm, respectively, and no
      statistically significant difference was found between lesion coordinates in the
      axial (p=0.37) and lateral (p=0.15) directions. Based on the ex vivo tissue
      experiments, we have demonstrated the feasibility of the proposed RF-based method
      for the localization of the center of HIFU-induced lesions.

PMID- 19163508
TI  - Diffusive coupling can induce synchronized periodic activity in neural networks.
AB  - Diffusive coupling also known as nearest-neighbor coupling is a common form of
      coupling but its role in the behavior of neural circuits is unclear. Previous
      experimental and theoretical studies have shown that potassium lateral diffusion
      coupling (i.e., diffusive coupling) was responsible for synchronization of
      neuronal activity. We tested the hypothesis that potassium lateral diffusion
      coupling is required to generate periodic epileptiform activity in a zero-Ca(2+)
      CA1 pyramidal neuron network model. The simulation results show that potassium
      lateral diffusion coupling is crucial for establishing a periodic synchronized
      epileptiform activity similar to that observed in experimental preparations. This
      results suggest that potassium lateral diffusion coupling - a physiological
      realization of the concept of diffusive coupling - can play a role in network
      behavior.

PMID- 19163510
TI  - 2-APB reduces the complexity of hippocampal gamma oscillations in rats.
AB  - Previous studies suggested that gamma oscillations in the brain are associated
      with higher order cognitive function including selective visual attention, motor
      task planning, sensory perception, working memory and dreaming REM sleep. These
      oscillations are mainly observed in cortical regions and also occurs in
      neocortical and subcortical areas and the hippocampus. In this paper, we
      investigate the influence of acute exposure to 2-APB exposure on the complexity
      of hippocampal gamma gamma oscillations. Our central hypothesis is that acute
      exposure to 2 APB significantly reduce the hippocampal gamma oscillations. In
      order to test this hypothesis, we use brain-slice recordings and the advanced
      nonlinear dynamical analysis method based on the Lempel-Ziv estimator. Our
      nonlinear dynamical analysis of brain slice recordings results suggested that 2
      APB exposure significantly reduces the hippocampal gamma oscillations.

PMID- 19163509
TI  - Assessment of hippocampal and autonomic neural activity by point process models.
AB  - The development of statistical models that accurately describe the stochastic
      structure of neural oscillations is a fast growing area in quantitative research.
      In developing a novel statistical paradigm based on Bayes' theorem and the theory
      of point processes, we focused our recent research on two applications. The first
      studies how hippocampal neural activity represents and transmits information,
      whereas the second is aimed at characterizing activity of the central autonomic
      network as involved in cardiovascular control.

PMID- 19163511
TI  - Assessing elderly persons' fall risk using spectral analysis on accelerometric
      data--a clinical evaluation study.
AB  - Falls are among the leading causes for morbidity, mortality and lasting
      functional disability in the elderly population. Several studies have shown the
      applicability of accelerometry to detect persons with a high fall risk. Most of
      these studies have been conducted under laboratory settings and without clear
      definition of 'fall risk' reference measures. The aim of our work is to provide a
      simple unsupervised method to assess the fall risk of elderly persons as measured
      by reference clinical fall risk assessment scores. Our method uses parameters
      computed by spectral analysis on triaxial accelerometer data recorded in a
      clinical setting, and is evaluated using simple logistic regression classifier
      models with reference to three clinical reference scores. The overall prediction
      accuracy of the models ranges from 65.5-89.1%, with sensitivity and specificity
      between 78.5-99% and 15.4-60.4%, respectively. Our results show that our simple
      method can be used to detect persons with a high fall risk with a fair to good
      predictive accuracy when tested against common clinical reference scores. Our
      parameters are independent of specific test procedures and therefore are suited
      for use in an unsupervised setting. Our future research will include the
      evaluation of our method in a large prospective study.

PMID- 19163512
TI  - Using wearable sensors to predict the severity of symptoms and motor
      complications in late stage Parkinson's Disease.
AB  - This paper is focused on the analysis of data obtained from wearable sensors in
      patients with Parkinson's Disease. We implemented Support Vector Machines (SVM's)
      to predict clinical scores of the severity of Parkinsonian symptoms and motor
      complications. We determined the optimal window length to extract features from
      the sensor data. Furthermore, we performed tests to determine optimal parameters
      for the SVM's. Finally, we analyzed how well individual tasks performed by
      patients captured the severity of various symptoms and motor complications.

PMID- 19163513
TI  - Wearable monitoring system for chronic cardio-respiratory diseases.
AB  - In this paper is presented the study leading to the implementation of an
      innovative sensing textile platform, based on a wearable monitoring system named
      Wealthy, where novel piezoresistive sensors have been integrated to increase
      system capability in the field of pulmonary and cardiovascular diseases
      monitoring. Two different typologies of textile sensors for plethysmograpic
      measurements have been characterized and compared to evaluate sensors
      performance, through electro-dynamic laboratory tests and in vivo measurements.
      The whole system allows continuous remote monitoring of electrocardiogram and
      impedance pneumography signals through textile electrodes, while piezoresistive
      fabric sensors placed at the abdominal and thoracic level are able to
      discriminate between different breathing patterns. All the signals have been
      acquired simultaneously allowing a comparative control of cardiopulmonary
      activity and artifact rejection, while a comparative study with standard BIOPAC
      MP30 respiratory transducers has been performed in basal condition.

PMID- 19163514
TI  - A system for respiratory motion detection using optical fibers embedded into
      textiles.
AB  - In this contribution, a first prototype for mobile respiratory motion detection
      using optical fibers embedded into textiles is presented. The developed system
      consists of a T-shirt with an integrated fiber sensor and a portable monitoring
      unit with a wireless communication link enabling the data analysis and
      visualization on a PC. A great effort is done worldwide to develop mobile
      solutions for health monitoring of vital signs for patients needing continuous
      medical care. Wearable, comfortable and smart textiles incorporating sensors are
      good approaches to solve this problem. In most of the cases, electrical sensors
      are integrated, showing significant limits such as for the monitoring of
      anaesthetized patients during Magnetic Resonance Imaging (MRI). OFSETH (Optical
      Fibre Embedded into technical Textile for Healthcare) uses optical sensor
      technologies to extend the current capabilities of medical technical textiles.

PMID- 19163515
TI  - Chair alarm for patient fall prevention based on gesture recognition and
      interactivity.
AB  - The Gesture Recognition Interactive Technology (GRiT) Chair Alarm aims to prevent
      patient falls from chairs and wheelchairs by recognizing the gesture of a patient
      attempting to stand. Patient falls are one of the greatest causes of injury in
      hospitals. Current chair and bed exit alarm systems are inadequate because of
      insufficient notification, high false-alarm rate, and long trigger delays. The
      GRiT chair alarm uses an array of capacitive proximity sensors and pressure
      sensors to create a map of the patient's sitting position, which is then
      processed using gesture recognition algorithms to determine when a patient is
      attempting to stand and to alarm the care providers. This system also uses a
      range of voice and light feedback to encourage the patient to remain seated
      and/or to make use of the system's integrated nurse-call function. This system
      can be seamlessly integrated into existing hospital WiFi networks to send
      notifications and approximate patient location through existing nurse call
      systems.

PMID- 19163516
TI  - Smooth muscle model for functional electrical stimulation applications:
      simulation of realistic bladder behavior under FES.
AB  - In this paper, we present a smooth muscle model which enables simulation of
      functional electrical stimulation (FES) induced contraction. The major novelty of
      this new version of our model is that it includes muscle cell calcium dynamics.
      We establish the relationship between calcium concentration and electrical
      potential of the membrane cell. Calcium concentration drives the microscopic
      mechanics of the muscle inducing contraction. We also refined the mechanical
      model: smooth muscles have slower dynamics than striated ones, it is therefore
      possible to neglect the second order terms in the differential equations.
      Validation of the model is achieved through the simulation of a well known
      example: the bladder electrical stimulation with a Finetech / Brindley implant.
      The obtained results are compared qualitatively with the experimental data
      available in the literature and show good consistency both in shape and time
      course. In order to obtain quantitative simulations, we need to perform the
      identification of the model through in-vivo testing on animals. Once this
      validation step is done, it will be possible to apply our methodology to human
      bladder neural stimulation.

PMID- 19163517
TI  - Modeling and identification of human neuromusculoskeletal network based on
      biomechanical property of muscle.
AB  - In this paper, we build a whole-body neuromusculoskeletal network model including
      somatic reflex, and identify its parameters through non-invasive measurements and
      statistical analysis. Such models are crucial for analyzing and estimating
      signals in the nervous system. Our neuromuscular model consists of two parts. The
      first part models the neuromuscular network that represents the relationships
      between the spinal nerve signals and muscle activities, which are then converted
      to muscle tensions using a physiological muscle dynamics model. The second part
      includes the feedback loops from muscle spindles and Golgi tendon organs to the
      spinal nerve that represent the somatic reflex using muscle length, velocity, and
      tension information. We demonstrate the consistency of the model by showing that
      a forward dynamics simulation of somatic reflex yields a motion similar to actual
      human response.

PMID- 19163518
TI  - Optimal design of musculoskeletal models using force field data.
AB  - We propose an optimal design framework for a musculoskeletal model. A six degrees
      of freedom generalized force field at an end effector is measured by activating a
      specific muscle in-situ. Given that we have a musculoskeletal simulation model
      with a set of undetermined design parameters, the framework chooses the optimal
      parameters which minimize the difference between simulated and measured force
      field data. To ensure generality, the framework is model independent, which means
      that any type of musculoskeletal model can be applied. As a generalized method, a
      PID (Proportional-Integral-Derivative) controller and an empirical Jacobian are
      used to correctly simulate the force field without suffering from numerical
      issues such as stability and indeterminacy. Case studies of the muscles of the
      rat hind limb show a satisfactory capability of the framework.

PMID- 19163519
TI  - A neuromusculoskeletal model exploring peripheral mechanism of tremor.
AB  - This paper studies the peripheral mechanism contributing to the tremor of human
      body. It is known that the reflex loops in peripheral nervous system have
      significant influences on the tremor. A neuromusculoskeletal model with several
      reflex loops is developed to explore the origin of tremor. The muscle model is
      developed based on a Hill-type muscle model. The feedback loops include the
      spindle organ, Golgi tendon organ and Renshaw cell. Their effects are
      investigated quantitatively in detail. Some results are in accordance with the
      previous research. Meanwhile, some new findings are proposed according to the
      simulation study.

PMID- 19163520
TI  - Fast orthogonal search method to estimate upper arm Hill-based muscle model
      parameters.
AB  - We propose a methodology to estimate subject-specific physiological parameters of
      Hill-based models of upper arm muscles. The methodology uses Hill-type candidate
      functions in the Fast Orthogonal Search (FOS) method to predict force at the
      wrist during elbow flexion and extension. To this end, surface EMG data from
      three muscles of the upper arm were recorded from 5 subjects as they performed
      isometric contractions at different elbow joint angles. Estimated muscle
      activation level and joint angle were utilized as inputs to the FOS model to
      obtain subject-specific estimates of optimal joint angle the Gaussian shape
      parameter for the force-length relationship for each muscle.

PMID- 19163521
TI  - Preterm labor--modeling the uterine electrical activity from cellular level to
      surface recording.
AB  - Uterine electrical activity is correlated to the appearance of uterine
      contractions. forceful contractions appear at the end of term. Therefore,
      understanding the genesis and the propagation of uterine electrical activity may
      provide an efficient tool to diagnose preterm labor. Moreover, the control of
      uterine excitability seems to have important consequences in the control of
      preterm labor. Modeling the electrical activity in uterine tissue is thus an
      important step in understanding physiological uterine contractile mechanisms and
      to permit uterine EMG simulation. Our model presented in this paper, incorporates
      ion channel models at the cell level, the reaction diffusion equations at the
      tissue level and the spatiotemporal integration at the uterine EMG reconstructed
      level. This model validates some key physiological observation hypotheses
      concerning uterine excitability and propagation.

PMID- 19163522
TI  - Angular domain optical imaging using a micromachined tunnel array and a Keplerian
      lens system.
AB  - Angular Domain Imaging (ADI) is a technique that selects quasi-ballistic photons
      exiting from a highly scattering medium by an array of silicon micromachined
      micro-tunnels. Each channel has a limited acceptance angle based on its geometry
      therefore those photons that traverse within the acceptance angle of the micro
      tunnels will be detected by the imager. In this paper, the ADI technique has been
      investigated by using newly micromachined tunnels with less spacing between the
      channels. Also, a Keplerian lens system is used to remove the diffracted light
      exiting from the tunnels that results due to internal reflection of scattered
      photons along the tunnel's walls. With these changes, improvements in the spatial
      resolution including sharper edges and definition were observed. The experiments
      show that the new setup can resolve test structure objects down to 100 mum
      embedded midway through a 2 cm long cuvette filled with 0.3% Intralipid solution
      in the 808 nm wavelength.

PMID- 19163523
TI  - The design and characterization of a digital optical breast cancer imaging
      system.
AB  - Optical imaging has the potential to play a major role in breast cancer screening
      and diagnosis due to its ability to image cancer characteristics such as
      angiogenesis and hypoxia. A promising approach to evaluate and quantify these
      characteristics is to perform dynamic imaging studies in which one monitors the
      hemodynamic response to an external stimulus, such as a valsalva maneuver. It has
      been shown that the response to such stimuli shows MARKED differences between
      cancerous and healthy tissues. The fast imaging rates and large dynamic range of
      digital devices makes them ideal for this type of imaging studies. Here we
      present a digital optical tomography system designed specifically for dynamic
      breast imaging. The instrument uses laser diodes at 4 different near-infrared
      wavelengths with 32 sources and 128 silicon photodiode detectors.

PMID- 19163524
TI  - Measurement of sublingual blood velocity as a tool for monitoring sepsis.
AB  - Measurements of sublingual blood velocity and blood flow were performed at normal
      body temperature and after both hot and cold stimulation. Laser speckle
      measurements of blood velocity were compared with measurements of blood flow
      obtained with a commercial laser Doppler flowmeter. Sublingual blood velocity
      increased in all subjects in response to both hot and cold stimulation as
      compared with that at normal temperature.

PMID- 19163525
TI  - High resolution mapping of cortical blood flow by mosaicing the laser speckle
      images.
AB  - Laser speckle imaging (LSI) has been implemented as a tool of acquiring two
      dimensional blood flow information. Using vascular segmentation techniques, we
      are able to obtain the cortical vascular blood flow distribution. Nevertheless,
      the conventional LSI methods have limitations of small imaging area and low
      dynamic range of contrast due to the ambient background field, dark current and
      anomalies in the circuits of CCD camera. In this study, we introduced an enhanced
      laser speckle contrast analysis (eLASCA) to improve the dynamic range of LASCA,
      then a high resolution of cerebral blood flow (CBF) was obtained by image
      mosaicing technique, including image registration and image fusion. The eLASCA
      based LSI mosaicing provides global anatomic details of cortical microvessels as
      well as the cortical vascular blood flow information.

PMID- 19163526
TI  - The forward problem algorithm based on modified element free Galerkin method for
      bioluminescence tomography.
AB  - As an emerging and promising molecular imaging modality, bioluminescence
      tomography (BLT) can reconstruct the internal light source with the photon
      fluence on the small animal surface to reveal non-invasive molecular and cellular
      activities directly. In order to obtain higher precision and better spatial
      resolution in source reconstruction, the solution accuracy for the forward
      problem of BLT should be improved as high as possible. In this contribution, we
      present a modified element free Galerkin method (MEFGM) to calculate photon
      propagation in the biological tissue. This method is based on moving least
      squares (MLS) approximation which requires only a series of nodes in the region
      of interest, so complicated meshing task can be avoided compared with finite
      element method (FEM). Furthermore, MLS shape functions are further modified to
      satisfy the delta function property, which can simplify the processing of
      boundary conditions in comparison with traditional meshless methods. Finally, the
      numerical simulation experiments demonstrate the effectiveness and feasibility of
      this proposed method by comparing the solution of MEFGM with that of FEM.

PMID- 19163527
TI  - Terahertz image processing methods for biomedical applications.
AB  - Terahertz imaging is in its early stages of development. Due to the sensitivity
      of terahertz radiation to biomolecules, several potential medical applications
      are being investigated. In this paper we present examples of our latest
      measurements of biological samples and explain how we extract frequency domain
      and time domain information from image data to probe sample structure and
      composition.

PMID- 19163528
TI  - Assessing the memorization of TV commercials with the use of high resolution EEG:
      a pilot study.
AB  - The present work intends to evaluate the functional characteristics of the
      cerebral network during the successful memory encoding of TV commercials. We
      estimated the functional networks in the frequency domain from a set of high
      resolution EEG data. High resolution EEG recordings were performed in a group of
      healthy subjects and the cortical activity during the observation of TV
      commercials was evaluated in several regions of interest coincident with the
      Brodmann areas (BAs). Summarizing the main results of the present study, a sign
      of the memorization of a particular set of TV commercials have been found in a
      group of investigated subjects with the aid of advanced modern tools for the
      acquisition and the processing of EEG data. The cerebral processes involved
      during the observation of TV commercials that were remembered successively by the
      population examined (RMB dataset) are generated by the posterior parietal
      cortices and the prefrontal areas, rather bilaterally and are irrespective of the
      frequency bands analyzed. Such results are compatible with previously results
      obtained from EEG recordings with superficial electrodes as well as with the
      brain activations observed with the use of MEG and fMRI devices.

PMID- 19163529
TI  - The SSVEP topographic scalp maps by canonical correlation analysis.
AB  - As the number of electrodes increases, topographic scalp mapping methods for
      electroencephalogram (EEG) data analysis are becoming important. Canonical
      correlation analysis (CCA) is a method of extracting similarity between two data
      sets. This paper presents an EEG topographic scalp mapping -based CCA for the
      steady-state visual evoked potentials (SSVEP) analysis. Multi-channel EEG data
      and the sinusoidal reference signal were used as the inputs of CCA. The output
      linear combination was then employed for mapping. Our experimental results prove
      the topographic scalp mapping-based CCA can instruct for the improvement of SSVEP
      based brain computer interface (BCI) system.

PMID- 19163530
TI  - Head modeling and cortical source localization in epilepsy.
AB  - In this study, we developed numerical methods for investigating the dynamics of
      epilepsy from multi-scale EEG recordings acquired simultaneously from the scalp
      (sEEG) and intracranial subdural and/or depth electrodes (iEEG) in patients
      undergoing pre-surgical evaluation at the epilepsy center of the Mayo Clinic
      (Rochester, MN). The data are analyzed using independent component analysis
      (ICA), which identifies and isolates independent signal components from multi
      channel recordings. A realistic individual head model was constructed for a
      patient undergoing pre-surgical evaluation. The forward problem of electro
      magnetic source localization was solved using the Boundary Element Method (BEM).
      Using this approach, we investigated the relationships between noninvasive and
      invasive source localization of human electrical brain data sources. A difference
      of about 1 cm was observed between sources estimated from sEEG and iEEG
      measurements.

PMID- 19163531
TI  - Assessment of neural dynamic coupling and causal interactions between independent
      EEG components from cognitive tasks using linear and nonlinear methods.
AB  - Over the past few years there has been an increased interest in studying the
      underlying neural mechanism of cognitive brain activity. In this direction, we
      study the brain activity based on its independent components instead of the EEG
      signal itself. Both linear and nonlinear synchronization measures are applied to
      EEG components, which are free of volume conduction effects and background noise.
      More specifically, a robust nonlinear state-space generalized synchronization
      assessment method and the recently introduced partial directed coherence are
      investigated in a working memory paradigm, during mental rehearsal of pictures.
      The latter is a linear method able to assess not only the independence of the
      brain regions, but also the direction of the statistically significant
      relationships. The results are in accordance with previous psychophysiology
      studies suggesting increased synchrony between prefrontal and parietal components
      during the rehearsal process, most prominently in gamma (ca. 40 Hz) band. This
      study indicates that functional connectivity during cognitive processes may be
      successfully assessed using independent components, which reflect distinct
      spatial patterns of activity.

PMID- 19163532
TI  - Optimal spatial resolution of epidural and subdural electrode arrays for brain
      machine interface applications.
AB  - Brain-machine interfaces (BMIs) have the potential to improve quality of life for
      thousands of motor-impaired individuals. Many different signal sources have been
      investigated for use in controlling a BMI, including scalp EEG, field potentials
      from inside and the surface of the cerebral cortex, and single-neuron action
      potentials. A relatively unexplored region for recording signals is the epidural
      space. This study attempts to help determine the optimal spatial resolution of
      epidural and subdural electrode arrays using both a mathematical model and
      spatial spectral analysis. For rats, optimal spacing for both epidural and
      subdural electrodes was approximately 0.7 mm.

PMID- 19163533
TI  - A Bayesian approach to peptide identification using accurate mass and time tags
      from LC-FTICR-MS proteomics experiments.
AB  - In high-throughput proteomics, one promising approach presently being explored is
      the Accurate Mass and Time (AMT) tag approach, in which reversed-phase liquid
      chromatography coupled to high accuracy mass spectrometry provide measurements of
      both the masses and chromatographic retention times of tryptic peptides in
      complex mixtures. These measurements are matched to the mass and predicted
      retention times of peptides in library. There are two varieties of peptides in
      the library: peptides whose retention time predictions are derived from previous
      peptide identifications and therefore are of high precision, and peptides whose
      retention time predictions are derived from a sequence-based model and therefore
      have lower precision. We present a Bayesian statistical model that provides
      probability estimates for the correctness of each match by separately modeling
      the data distributions of correct matches and incorrect matches. For matches to
      peptides with high-precision retention time predictions, the model distinguishes
      correct matches from incorrect matches with high confidence. For matches to
      peptides having low-precision retention time predictions, match probabilities do
      not approach certainty; however, even moderate probability matches may provide
      biologically interesting findings, motivating further investigations.

PMID- 19163534
TI  - An information theoretic method of microarray probe design for genome
      classification.
AB  - In recent years, oligo microarrays, or more commonly-known DNA chips, have had a
      major impact in disease diagnosis, drug discovery, and gene identification.
      Microarrays contain Nmer DNA fragments, or oligos, in a series of 'wells' placed
      across the chip, where each well contains thousands of the same fragments and
      acts as a probe that detects the amount of a specific fragment. A recent use for
      microarrays is for identification of genomes, such as pathogens. In current
      techniques, probes that detect unique gene regions of particular species are
      selected to be placed on the microarray, using the assumption that if one gene
      unique to a pathogen species can be detected, then the pathogen can be
      classified. This approach is useful, but the technology relies on finding the
      gene sequences that are divergent enough to be used as a genomic identifier and
      robust to cross-hybridization. In our work, we present a method to choose the
      most unique probes between two organisms. We accomplish this by choosing the
      oligo probes that maximize the level of divergence between the genomes,
      calculated by three different information-theoretic measures. We show the results
      for a 12-mer and 25-mer oligo pathogen probe set and that our method chooses
      probes less likely to cross-hybridize.

PMID- 19163535
TI  - SNP sets selection under mutual information criterion, application to F7/FVII
      dataset.
AB  - One of the main goals of human genetics is to find genetic markers related to
      complex diseases. In blood coagulation process, it is known that genetic
      variability in F7 gene is the most responsible for observed variations in FVII
      levels in blood. In this work, we propose a method for selecting sets of Single
      Nucleotide Polymorphisms (SNPs) significantly correlated with a phenotype (FVII
      levels). This method employs a feature selection algorithm (variant of Sequential
      Forward Selection, SFS) based on a criterion of statistical significance of a
      mutual information functional. This algorithm is applied to a sample of
      independent individuals from the GAIT project. Main SNPs found by the algorithm
      are in correspondence with previous results published using family-based
      techniques.

PMID- 19163536
TI  - Mining knowledge for the methylation status of CpG islands using alternating
      decision trees.
AB  - CpG island (CpGI) methylation is an epigenetic modification that occurs in
      eukaryotes and is based on the addition of a methyl group to the number 5 carbon
      of the pyrimidine ring of cytosine. When methylation of a CpGI occurs, the
      associated gene (if any) is not expressed [1]. Aberrant methylation is thought to
      be a causative agent in disease [2] and drug sensitivity [3], [4]. In this work,
      we have predicted the methylation status of CpGIs in human chromosome 21 using
      sequence patterns. These patterns showed a significantly different distribution
      between methylated and unmethylated islands in a previous work [5]. Using C4.5
      with bagging and cost-sensitive learning, we achieved 85.6% accuracy, 82.8%
      sensitivity, and 86.4% specificity.We then constructed 1000 alternating decision
      trees using a bootstrapping method and analyzed the nodes that were conserved
      between the trees. This allowed us to find specific combinations of sequence
      patterns that distinguished between methylated and unmethylated CpGIs. Analysis
      of these characteristics offers certain insight into the conditions that permit
      or prevent methylation.

PMID- 19163537
TI  - Integrated peptide and glycan biomarker discovery using MALDI-TOF mass
      spectrometry.
AB  - Quantitative comparison of peptides and glycans in serum is conducted using
      matrix-assisted laser desorption/ionization-time of flight mass spectrometry
      (MALDI-TOF MS) to identify biomarkers. A peak selection algorithm is developed to
      identify a panel of integrated peptide and glycan peaks to distinguish
      hepatocellular carcinoma (HCC) cases from high-risk population of patients with
      chronic liver disease (CLD). Candidate peptide and glycan markers selected
      frequently in multiple runs of the algorithm are presented. The performance of
      these markers is evaluated in terms of their ability to distinguish HCC cases
      from patients with CLD in a blinded validation set.

PMID- 19163538
TI  - Intelligible machine learning with malibu.
AB  - malibu is an open-source machine learning work-bench developed in C/C++ for high
      performance real-world applications, namely bioinformatics and medical
      informatics. It leverages third-party machine learning implementations for more
      robust bug-free software. This workbench handles several well-studied supervised
      machine learning problems including classification, regression, importance
      weighted classification and multiple-instance learning. The malibu interface was
      designed to create reproducible experiments ideally run in a remote and/or
      command line environment. The software can be found at:
      http://proteomics.bioengr. uic.edu/malibu/index.html.

PMID- 19163539
TI  - Automated creation of transparent fuzzy models based on decision trees-
      application to diabetes diagnosis.
AB  - In this paper we propose a novel approach for the simplification of a fuzzy
      model. Initially, we employ a methodology for the automated generation of fuzzy
      models based on decision trees. The methodology is realized in three stages.
      Initially, a crisp model is created from a decision tree, induced from the data.
      Then, the crisp model it is transformed to a fuzzy one. Finally, in the third
      stage, all parameters entering the fuzzy model are optimized. The simplification
      technique is based on the pruning of the initial decision tree. The proposed
      approach is applied for diabetes diagnosis and the obtained results indicate its
      efficiency and effectiveness.

PMID- 19163540
TI  - Predicting ICU hemodynamic instability using continuous multiparameter trends.
AB  - BACKGROUND: Identifying hemodynamically unstable patients in a timely fashion in
      intensive care units (ICUs) is crucial because it can lead to earlier
      interventions and thus to potentially better patient outcomes. Current alert
      algorithms are typically limited to detecting dangerous conditions only after
      they have occurred and suffer from high false alert rates. Our objective was to
      predict hemodynamic instability at least two hours before a major clinical
      intervention (e.g., vasopressor administration), while maintaining a low false
      alert rate. STUDY POPULATION: From the MIMIC II database, containing ICU minute
      by-minute heart rate (HR) and invasive arterial blood pressure (BP) monitoring
      trend data collected between 2001 and 2005, we identified 132 stable and 104
      unstable patients that met our stability-instability criteria and had sufficient
      data points. METHOD: We first derived additional physiological parameters of
      shock index, rate pressure product, heart rate variability, and two measures of
      trending based on HR and BP. Then we developed 220 statistical features and
      systematically selected a small set to use for classification. We applied multi
      variable logistic regression modeling to do classification and implemented
      validation via bootstrapping. RESULTS: Area under receiver-operating curve (ROC)
      0.83+/-0.03, sensitivity 0.75+/-0.06, and specificity 0.80+/-0.07; if the
      specificity is targeted at 0.90, then the sensitivity is 0.57+/-0.07. Based on
      our preliminary results, we conclude that the algorithms we developed using HR
      and BP trend data may provide a promising perspective toward reliable predictive
      alerts for hemodynamically unstable patients.

PMID- 19163541
TI  - A hierarchical, ontology-driven Bayesian concept for ubiquitous medical
      environments--a case study for pulmonary diseases.
AB  - The present paper extends work on an existing computer-based Decision Support
      System (DSS) that aims to provide assistance to physicians as regards to
      pulmonary diseases. The extension deals with allowing for a hierarchical
      decomposition of the task, at different levels of domain granularity, using a
      novel approach, i.e. Hierarchical Bayesian Networks. The proposed framework uses
      data from various networking appliances such as mobile phones and wireless
      medical sensors to establish a ubiquitous environment for medical treatment of
      pulmonary diseases. Domain knowledge is encoded at the upper levels of the
      hierarchy, thus making the process of generalization easier to accomplish. The
      experimental results were carried out under the Pulmonary Department, University
      Regional Hospital Patras, Patras, Greece. They have supported our initial beliefs
      about the ability of Bayesian networks to provide an effective, yet semantically
      oriented, means of prognosis and reasoning under conditions of uncertainty.

PMID- 19163542
TI  - Temporal trend analysis in personal health records.
AB  - The creation of a universal standard for electronic medical records (EMR) remains
      a work in progress. The existence of a standard EMR that can be accessed by
      medical professionals anywhere in the world as well as by the patient will have a
      significant impact on the way that medicine is practiced. In addition to having
      information readily available, it would present the possibility to do individual
      trend analysis on each patient based on information accumulated over a lifetime.
      This information would permit diagnosis based on the individual rather than
      solely on population statistics. A comprehensive system for performing trend
      analysis on the multitude of data types relevant to medical decision making
      requires the creation and integration of a number of methods. A general approach
      based on a hybrid combination of automated decision support methods is described
      and illustrated for using trend data applied to cardiac diagnosis. The methods
      are general and can be applied to any application area.

PMID- 19163543
TI  - Emergent trend detection in diurnal activity.
AB  - When monitoring elders' daily routines, it is desirable to track significant
      deviations from a baseline pattern, as consecutive, aberrant days may foreshadow
      a need for medical attention. However, many traditional, unsupervised methods for
      pattern classification are ill-suited for this task, as they are incapable for
      adapting to additive datasets. To surmount this shortcoming, we establish a
      framework for recognizing temporal trends in feature data extracted from passive
      sensors.

PMID- 19163544
TI  - Regression forecasting of patient admission data.
AB  - Forecasting is an important aid in many areas of hospital management, including
      elective surgery scheduling, bed management, and staff resourcing. This paper
      describes our work in analyzing patient admission data and forecasting this data
      using regression techniques. Five years of Emergency Department admissions data
      were obtained from two hospitals with different demographic techniques. Forecasts
      made from regression models were compared with observed admission data over a 6
      month horizon. The best method was linear regression using 11 dummy variables to
      model monthly variation (MAPE=1.79%). Similar performance was achieved with a 2
      year average, supporting further investigation at finer time scales.

PMID- 19163545
TI  - Ethics in biomedical engineering.
AB  - This session focuses on a number of aspects of the subject of Ethics in
      Biomedical Engineering. The session starts by providing a case study of a company
      that manufactures artificial heart valves where the valves were failing at an
      unexpected rate. The case study focuses on Biomedical Engineers working at the
      company and how their education and training did not prepare them to deal
      properly with such situation. The second part of the session highlights the need
      to learn about various ethics rules and policies regulating research involving
      human or animal subjects.

PMID- 19163546
TI  - Automatic identification of epilepsy by HOS and power spectrum parameters using
      EEG signals: a comparative study.
AB  - Epilepsy is characterized by the spontaneous and unforeseeable occurrence of
      seizures, during which the perception or behavior of patients is disturbed. An
      automatic system that detects seizure onsets would allow patients or the people
      near them to take appropriate precautions, and could provide more insight into
      these phenomena. The use of non-linear features motivated by the higher order
      spectra (HOS) had been reported to be a promising approach to differentiate
      between normal, background (pre-ictal) and epileptic EEG signals. In this work,
      the features are extracted from the power spectrum and the bispectrum. Their
      performance is studied by feeding them to a Gaussian mixture model (GMM)
      classifier. Results show that with selected HOS based features, we were able to
      achieve 93.11% compared to classification accuracy of 88.78% as that of features
      derived from PSD.

PMID- 19163547
TI  - Quantifying the causal interactions in the brain using a measure of directed
      transinformation.
AB  - Most of the brain's cognitive functions rely on the coordinated interactions of
      neuronal sources that are distributed within and across specialized brain areas.
      It is important to quantify these temporal interactions directly from
      neuroimaging data such as the electroencephalogram (EEG). A variety of measures
      have been proposed to quantify the neural interactions including linear
      correlation measures and nonlinear information theoretic measures. An important
      aspect of neural interactions is the direction of the information flow, i.e., the
      causal interaction between the different regions. In this paper, we propose using
      a directed transinformation measure (T measure) to quantify these causal
      interactions. This measure is a generalization of Granger causality and
      quantifies both the linear and nonlinear interactions between the signals. The
      proposed measure is applied to both simulated and real EEG signals and is shown
      to be sensitive to the dependencies between signals.

PMID- 19163548
TI  - Hilbert-Huang Spectrum as a new field for the identification of EEG event related
      de-/synchronization for BCI applications.
AB  - Brain Computer Interfaces (BCI) usually utilize the suppression of mu-rhythm
      during actual or imagined motor activity. In order to create a BCI system, a
      signal processing method is required to extract features upon which the
      discrimination is based. In this article, the Empirical Mode Decomposition along
      with the Hilbert-Huang Spectrum (HHS) is found to contain the necessary
      information to be considered as an input to a discriminator. Also, since the HHS
      defines amplitude and instantaneous frequency for each sample, it can be used for
      an online BCI system. Experimental results when the HHS applied to EEG signals
      from an on-line database (BCI Competition III) show the potentiality of the
      proposed analysis to capture the imagined motor activity, contributing to a more
      enhanced BCI performance.

PMID- 19163549
TI  - Comparing a supervised and an unsupervised classification method for burst
      detection in neonatal EEG.
AB  - Hidden Markov Models (HMM) and Support Vector Machines (SVM) using unsupervised
      and supervised training, respectively, were compared with respect to their
      ability to correctly classify burst and suppression in neonatal EEG. Each
      classifier was fed five feature signals extracted from EEG signals from six full
      term infants who had suffered from perinatal asphyxia. Visual inspection of the
      EEG by an experienced electroencephalographer was used as the gold standard when
      training the SVM, and for evaluating the performance of both methods. The results
      are presented as receiver operating characteristic (ROC) curves and quantified by
      the area under the curve (AUC). Our study show that the SVM and the HMM exhibit
      similar performance, despite their fundamental differences.

PMID- 19163550
TI  - Single-trial analysis of the auditory N100 improves separation of normal and
      schizophrenia subjects.
AB  - The N100 component of the auditory evoked potential (EP) has been recently used
      to study sensory gating deficits in schizophrenia subjects compared to normal
      controls. Previously, we used selective averaging to show phase synchronization
      differences in brain activity between the two populations. In this study, we
      employed our recently developed iterative independent component analysis (iICA)
      procedure to measure single-trial EPs in the context of a double-stimulus
      paradigm. Using the amplitude and latency of the N100 components of the first and
      second stimuli responses obtained from iICA and four different classification
      algorithms we were able to accurately classify subjects with 100% sensitivity and
      100% specificity. In contrast, the same amplitude and latency features computed
      from average EPs provided only 69% classification accuracy, with 63% sensitivity
      and 75% specificity, respectively. We conclude that inter-trial temporal
      variability plays a significant role in the well-known sensory gating deficits
      found in schizophrenia patients.

PMID- 19163551
TI  - Assessment of the cardiovascular regulation during robotic assisted locomotion in
      normal subjects: autoregressive spectral analysis vs empirical mode
      decomposition.
AB  - Robotic assisted locomotion systems are recently gaining appreciation as methods
      to rehabilitate individuals with lost sensory motor function. In the present
      study we compare autoregressive power spectral analysis and empirical mode
      decomposition (EMD) applied to the analysis of short-term heart period
      variability regarding their ability to typify autonomic response during a robotic
      assisted locomotion session consisting in the following phases: 1) sitting
      position; 2) standing position; 3) suspension during subject instrumentation; 4)
      robotic assisted treadmill locomotion with partial body weight support; 5)
      standing recovery after exercise. Results showed a significant tachycardia during
      the suspension phase, but no significant changes of spectral indexes. On the
      contrary, when spectral indexes were derived according to EMD, changes were
      evidenced during the suspension and walking phases. The EMD method is more
      powerful than autoregressive spectral analysis in detecting variations of
      parasympathetic and sympathetic modulations elicited by a robotic-assisted
      locomotion protocol.

PMID- 19163552
TI  - Application of Hilbert-Huang transform for the study of motor imagery tasks.
AB  - A motor based Brain-Computer Interface (BCI) translates the subject's motor
      intention into a control signal by means of the method which extracts
      characteristic feature from EEG recorded from the scalp. In this paper, the EEG
      signal recorded during three motor imagery tasks, which were imagination of left
      hand, right hand and foot movements, was investigated. A novel method named
      Hilbert-Huang transform (HHT) is introduced to extract the feature from signal.
      Firstly, raw signal is decomposed using Empirical Mode Decomposition (EMD). And
      then, several Intrinsic Mode Functions (IMF) are gained. For further study, the
      IMFs whose main frequency is higher than 5 Hz are selected. Secondly, based on
      the IMFs selected above, Hilbert spectrum is calculated. In each motor imagery
      task, local instantaneous energies, within specific frequency band of electrode
      C3 and C4, are selected as the features. A three-layer BP Neural Network
      classifier is structured for pattern classification. The classification results
      show that HHT can be used in EEG-based BCI research as a method to analysis non
      linear and non-stationary signal.

PMID- 19163553
TI  - Gait pattern classification using compact features extracted from intrinsic mode
      functions.
AB  - Recent research work indicates that gait patterns are both non-linear and non
      stationary signals and they can be analyzed using empirical mode decomposition.
      This paper describes gait pattern classification using features that are obtained
      by performing discrete cosine transforms (DCT) on intrinsic mode functions of
      five different human gait patterns. The DCT provides a compact 8-dimensional
      feature vector for gait pattern classification. Fifty two subjects participated
      in the experiment. The classification was performed using a Gaussian mixture
      model and an overall accuracy of 90.2% was achieved.

PMID- 19163554
TI  - Robust peak detection of pulse waveform using height ratio.
AB  - The automatic recognition of pulse waveform is the key in the research of
      computerized pulse diagnosis. The peak detection is important in the extraction
      of the features of pulse waveform in time domain. In this paper, we proposed a
      robust peak detection algorithm of pulse waveform based on the ratio of peak
      height. The results demonstrate that the proposed algorithm is robust against
      unspecific noise and baseline drift of pulse waveform. The proposed algorithm can
      be applied into other quasi-periodic physiological signals too.

PMID- 19163555
TI  - Sleep onset estimator: evaluation of parameters.
AB  - The electroencephalographic (EEG) alterations during the human sleep onset
      (falling asleep period) has been evaluated by several studies in the past.
      However, the analysis part has been limited due to standard signal processing
      methods. This paper has attempted to evaluate a number of advanced parameters for
      improved sleep onset estimation, such as EEG non-parametric coherence, power
      frequency and spectral band power. These parameters can be utilised in an on-line
      algorithm design for neurofeedback applications.

PMID- 19163556
TI  - On-line automatic detection of driver drowsiness using a single
      electroencephalographic channel.
AB  - In this paper, an on-line drowsiness detection algorithm using a single
      electroencephalographic (EEG) channel is presented. This algorithm is based on a
      means comparison test to detect changes of the alpha relative power ([8-12]Hz
      band). The main advantage of the method proposed is that the detection threshold
      is completely independent of drivers and does not need to be tuned for each
      person. This algorithm, which works on-line, has been tested on a huge dataset
      representing 60 hours of driving and give good results with nearly 85% of good
      detections and 20% of false alarms.

PMID- 19163557
TI  - On the propagation analysis of electrohysterographic signals.
AB  - Premature birth is a leading cause of fetal mortality and long-term morbidity.
      The effective treatment of preterm uterine contractions requires new methods for
      predicting delivery. The electrohysterographic (EHG) signal is a measure of the
      bioelectrical process underlying the uterine contraction. The analysis of
      parameters derived from the EHG signal can therefore provide fundamental
      information for the prognosis of labor. In this paper, we focus on the
      propagation of the EHG signal recorded during delivery by multiple electrodes.
      For the inter-electrode delay assessment and propagation analysis, two different
      methods are implemented. One is based on the prior estimation of the uterine
      mechanical activity by EHG signal processing. The delay is then calculated by the
      cross-correlation function between the mechanical activity estimated at each
      sensor. The other method is a high temporal resolution adaptive delay estimator
      that operates directly on EHG signals. The previously demonstrated accuracy of
      the mechanical estimates and the agreement between the delays provided by the
      methods confirm the tight relationship between the mechanical and electrical
      activity of the uterus. However, our results suggest that a higher temporal
      resolution delay estimator is preferred.

PMID- 19163558
TI  - Applying time, frequency and nonlinear features from nocturnal oximetry to OSA
      diagnosis.
AB  - This study is aimed to improve the diagnostic ability of blood oxygen saturation
      (SaO(2)) in obstructive sleep apnea (OSA) detection. We studied 74 patients
      suspected of suffering from OSA. Ten characteristics were derived from each SaO2
      recording: arithmetic mean, variance, skewness and kurtosis from both time and
      frequency domains, central tendency measure and Lempel-Ziv complexity. The
      diagnostic ability of each feature was assessed by means of a receiver operating
      characteristics (ROC) analysis. Additionally, forward stepwise logistic
      regression (LR) was applied. The kurtosis in the time domain and the nonlinear
      measure of complexity were automatically selected. This methodology reached 93.2%
      sensitivity, 80.0% specificity and 87.8% accuracy, improving the results from
      each feature individually. Our study showed that common statistics in the time
      and frequency domains and nonlinear features could provide additional and
      complementary information to help in OSA diagnosis.

PMID- 19163559
TI  - Analysis of coherence between sleep EEG and ECG signals during and after
      obstructive sleep apnea events.
AB  - This study presents the first successful preliminary attempt to directly
      investigate the interactions of power spectra of sleep EEG and ECG signals of
      patients with obstructive sleep apnea syndrome (OSAS) by coherence analysis. ECG
      and EEG signals were collected from 8 OSAS patients and 3 healthy subjects.
      Coherence between two signals over different frequency bands(0-128 Hz) were
      calculated for normal breathing events, obstructive sleep apnea (OSA) events and
      events following OSA terminations (with/without arousals) in non-REM as well as
      REM sleep. Overall coherence of ECG and EEG in REM sleep is higher than that in
      non-REM sleep. A significant (p=0.0164) difference of coherence in the range of
      10-5 Hz was found among normal, OSA and termination events in REM sleep. The
      results could be useful in detecting OSA events or OSA related arousals to
      characterize sleep fragmentation from ECG and EEG signals.

PMID- 19163560
TI  - EEG signal classification method based on fractal features and neural network.
AB  - In this paper, we propose a method to classify electroencephalogram (EEG) signal
      recorded from left- and right-hand movement imaginations. Three subjects (two
      males and one female) are volunteered to participate in the experiment. We use a
      technique of complexity measure based on fractal analysis to reveal feature
      patterns in the EEG signal. Effective algorithm, namely, detrended fluctuation
      analysis (DFA) has been selected to estimate embedded fractal dimension (FD)
      values between relaxing and imaging states of the recorded EEG signal. To show
      the waveform of FDs, we use a windowing-based method or called time-dependent
      fractal dimension (TDFD) and the Kullback-Leibler (K-L) divergence. Two feature
      parameters; K-L divergence and different expected values are proposed to be input
      variables of the classifier. Finally, featured data are classified by a three
      layer feed-forward neural network based on a simple backpropagation algorithm.
      Experimental results can be considerably applied in a brain-computer interface
      (BCI) application and show that the proposed method is more effective than the
      conventional method by improving average classification rates of 87.5% and 88.3%
      for left- and right-hand movement imagery tasks, respectively.

PMID- 19163561
TI  - Early detection of neurodegeneration in brain ischemia by manganese-enhanced MRI.
AB  - This study aims to employ in vivo manganese-enhanced MRI (MEMRI) to detect
      neurodegenerative changes in two models of brain ischemia, photothrombotic
      cortical injury (PCI) and transient middle cerebral artery occlusion (MCAO) in
      rodents. After systemic Mn(2+) injection to both ischemic models, a close pattern
      of T1-weighted hyperintensity was observed throughout different brain regions in
      comparison to the distribution of GFAP, MnSOD and GS immunoreactivities, whereby
      conventional MRI could hardly detect such. In addition, the infarct volumes in
      the posterior parts of the brain had significantly reduced after Mn(2+) injection
      to the MCAO model. It is suggested that exogenous Mn(2+) injection may provide
      enhanced MEMRI detection of oxidative stress and gliosis early after brain
      ischemia. Manganese may also mediate infarctions at remote brain regions in
      transient focal cerebral ischemia before delayed secondary damage takes place.

PMID- 19163562
TI  - Automatic compartmental decomposition for 3D MR images of human brain.
AB  - A new method is developed to automatically decompose human brain MR images into
      cerebrum, cerebellum and brainstem. It utilizes the partial differential
      equations based shape bottlenecks algorithm to segment an interior brain tissue
      region into three compartmental seeds. Then the compartmental decomposition is
      obtained by reconstructing the compartments from the seeds according to the
      compartment boundary knowledge defined with partial volume information. This
      method was validated against manual segmentations of 35 T1-weighted MR images. It
      was demonstrated to be accurate and robust, and the mean Dice coefficients for
      cerebrum, cerebellum and brainstem were 0.99, 0.98 and 0.82, respectively.

PMID- 19163563
TI  - Neonatal probabilistic models for brain, CSF and skull using T1-MRI data:
      preliminary results.
AB  - Inappropriate results may be produced if one uses adult or pediatric atlases for
      evaluation of neonatal cerebral images for morphological studies. This is mainly
      due to anatomical particularities typical for this early stage of development. In
      this paper, we describe the construction of a digital neonatal brain atlas from a
      set of images of neonates aged between 39 and 42 weeks. It consists of
      probabilistic models for brain, cerebrospinal fluid (CSF) and skull. In the first
      step, the selected images are segmented automatically followed by manual
      correction. In the second step, the images are normalized to a stereotaxic space
      defined by the neonatal brain atlas template GRAMFC_T(39-42) using a popular
      normalization algorithm implemented in Statistical Parametric Mapping (SPM). The
      normalization parameters of individual subjects are then used to resample the
      corresponding brain, CSF and skull. Finally, to construct the probabilistic
      models, the average is computed for each voxel location. The atlas might be used
      for different applications such as source localization or neonatal structural
      image analysis.

PMID- 19163564
TI  - Inhomogeneity compensation for MR brain image segmentation using a multi-stage
      FCM-based approach.
AB  - Intensity inhomogeneity or intensity non-uniformity (INU) is an undesired
      phenomenon that represents the main obstacle for MR image segmentation and
      registration methods. Various techniques have been proposed to eliminate or
      compensate the INU, most of which are embedded into clustering algorithms. This
      paper proposes a multiple stage fuzzy c-means (FCM) based algorithm for the
      estimation and compensation of the slowly varying additive or multiplicative
      noise, supported by a pre-filtering technique for Gaussian and impulse noise
      elimination. The slowly varying behavior of the bias or gain field is assured by
      a smoothening filter that performs a context dependent averaging, based on a
      morphological criterion. The experiments using 2-D synthetic phantoms and real MR
      images show, that the proposed method provides accurate segmentation. The
      produced segmentation and fuzzy membership values can serve as excellent support
      for 3-D registration and segmentation techniques.

PMID- 19163565
TI  - Abnormalities in MRI traits of corpus callosum in autism subtype.
AB  - A number of studies have documented that autism has a neurobiological basis, but
      the anatomical extent of these neurobiological abnormalities is largely unknown.
      In this paper, we apply advanced computational techniques to extract 3D models of
      the corpus callosum (CC) and subsequently analyze the volumetric deficit of the
      total CC and its five sub-regions in a homogeneous group of autistic children.
      Moreover, we explore new MRI traits based on the oriented bounding rectangle of
      the CC, which are the length, width and aspect ratio of the bounding rectangle.
      These measurements as well as the volumes are compared between patients and
      controls using t-tests. The results reveal significant reduction in all sub
      regions of the CC and some MRI traits in the patients.

PMID- 19163566
TI  - Image based diagnosis of cortical cataract.
AB  - An automatic approach to detect cortical opacities and grade the severity of
      cortical cataract from retro-illumination images is proposed. The spoke-like
      feature of cortical opacity is employed to separate from other opacity type. The
      proposed algorithms were tested by images from a community study. The success
      rate of region of interest (ROI) detection is 98.2% for 611 images. For 466
      images tested, the mean error of opacity area detection is 3.15% compared with
      human grader and 85.6% of exact cortical cataract grading is obtained. The
      experimental results show that the proposed approach is promising in clinical
      diagnosis.

PMID- 19163567
TI  - Computer-aided diagnosis scheme for classification of lacunar infarcts and
      enlarged Virchow-Robin spaces in brain MR images.
AB  - The detection of asymptomatic lacunar infarcts on magnetic resonance (MR) images
      is important because their presence indicates an increased risk of severe
      cerebral infarction. However, accurate identification of lacunar infarcts on MR
      images is often hard for radiologists because of the difficulty in distinguishing
      lacunar infarcts and enlarged Virchow-Robin spaces. Therefore, we developed a
      computer-aided diagnosis (CAD) scheme for the classification of lacunar infarcts
      and enlarged Virchow-Robin spaces. Our database consisted of T1- and T2- weighted
      images obtained from 109 patients. The locations of lacunar infarcts and enlarged
      Virchow-Robin spaces were determined by an experienced neuroradiologist. It
      included 89 lacunar infarcts and 20 enlarged Virchow-Robin spaces. We first
      enhanced the lesions in T2-weighted image by using the white top-hat
      transformation. A gray-level thresholding was then applied to the enhanced image
      for the segmentation of lesions. From the segmented lesions, we determined image
      features, such as size, shape, location, and signal intensities in T1- and T2-
      weighted images. A neural network was then employed for distinguishing between
      lacunar infarcts and enlarged Virchow-Robin spaces. Our computerized method was
      evaluated by using a leave-one-out method. The result indicated that the area
      under the ROC curve was 0.945. Therefore, our CAD scheme would be useful in
      assisting radiologists for diagnosis of silent cerebral infarctions in MR images.

PMID- 19163568
TI  - 3D mutifractal analysis: a new tool for epileptic fit sources detection in SPECT
      images.
AB  - One of the imaging modalities used for the diagnosis of epilepsy is SPECT (Single
      Photon Emission Computed Tomography). Ictal and interictal images are registered
      to MR images (SISCOM (Substracted Ictal Spect COregistred to MR) to delineate the
      sources. However, in some cases and for many reasons, the used method does not
      lead to precise delimitation of epileptic fit sources. In this case, works have
      been investigated on group's studies or in combining others modalities like EEG
      (Electroencephalography). This study investigates the possibility of using a
      mathematic model for the image texture to detect the changes on SPECT images.
      Beyond encouraging preliminary results concerning the multifractal analysis to
      distinguish volunteers and epileptic patients, our aim was to detect sources by
      the singularity spectrum compute. The experiment is divided into two phases.
      First, we developed a 3D method for the singularity spectrum compute. In the test
      phase, we applied this multifractal spectrum to the sources detection on SPECT
      images. The results obtained on a base of seven patients show that the proposed
      method is encouraging. Indeed, the detections of epileptic fit sources obtained
      were in agree with the expert diagnostic.

PMID- 19163569
TI  - A PCA-based approach to the representation and recognition of MR brain
      midsagittal plane images.
AB  - The midsagittal plane (MSP) of brain images is a key landmark used for many
      processing and analysis procedures associated with diagnosis, and intervention
      planning for the brain. In this paper, we propose to represent MSP images with
      features from principal component analysis (PCA). MSP images are extracted from
      43 brain MRI volumes of different subjects. Images are represented as linear
      combinations of a set of eigen images which define the eigenspace that best
      describes the variation distribution of the set of images. The results of tests
      using planes extracted with slight orientational variations about the MSP show
      100% recognition accuracy for planes varied under 0.5 degrees, and its robustness
      to MSP extraction error within variations of 1 degree in magnitude. The
      validation of this method with different MSP images yields a recognition accuracy
      of 88.6%.

PMID- 19163570
TI  - A statistical atlas-based technique for automatic segmentation of the first
      Heschl's gyrus in human auditory cortex from MR images.
AB  - We present an automatic method for the segmentation of the first transverse
      temporal gyrus of Heschl (HG), the morphological marker for primary auditory
      cortex in humans. The proposed technique utilizes a statistical anatomical atlas
      of the gyrus, generated from a set of training samples using principal component
      analysis. The training set consists of MRI data from 12 subjects with the
      corresponding Heschl's gyri manually labeled in each hemisphere (separate atlases
      were generated for each hemisphere). We used a leave-one-out approach to
      automatically segment Heschl's gyri in both hemispheres from the MR image data
      using generated atlases. We assessed the accuracy of this atlas-based technique
      by using it to segment the HG region from several test cases and finding the
      overlap between the segmented and labeled HG regions. Results demonstrated more
      than 75% and 83% accuracy in the extraction of the HG volumes in the left and
      right hemispheres, respectively. It is expected that the proposed tool can be
      adapted to extract other anatomical regions in the brain.

PMID- 19163571
TI  - Comparison of tissue segmentation algorithms in neuroimage analysis software
      tools.
AB  - Accurate segmentation of different brain tissues is of much importance in
      magnetic resonance imaging. This paper presents a comparison of the existing
      segmentation algorithms that are deployed in the neuroimaging community as part
      of two widely used software packages. The results obtained in this comparison can
      be used to select the appropriate segmentation algorithm for the neuroimaging
      application of interest. In addition to the entire brain area, a comparison is
      carried out for the subcortical region of the brain in terms of its gray matter
      composition.

PMID- 19163572
TI  - Brain-mapping using robotized TMS.
AB  - We present first results of brain-mapping using robotic Transcranial Magnetic
      Stimulation. This non-invasive procedure enables the reliable detection of the
      representation of individual muscles or muscle groups in the motor-cortex. The
      accuracy is only exceeded by direct electrical stimulation of the brain during
      surgery. Brain-mapping using robotic TMS can also be used to detect displacements
      of brain regions caused by tumors. The advantage of TMS is that it is non
      invasive. In this study, we compare results from statistical mapping with robotic
      TMS to results achieved from direct stimulation done during tumor surgery. To our
      knowledge this is the first study of this type. We mapped the representation of
      three muscle groups (forearm, pinky and thumb) in tumor patients with the robot
      aided TMS protocol and with direct stimulation. The resulting maps agree within
      5mm.

PMID- 19163573
TI  - Cortical complexity analysis of patients with bipolar disorder using three
      dimensional gyrification index.
AB  - Bipolar disorder (BD) is a common affective disorder. In morphometric brain
      imaging studies, BD subjects have atrophic gray matter, especially in the
      prefrontal area. These structural abnormalities could involve the change of
      cortical shape. Gyrification index (GI) is a useful metric to measure the degree
      of cortical complexity. This work aims to compare the cortical development
      between bipolar patients and healthy controls using GI. No significant difference
      was detected between two groups. However, we found asymmetry pattern of cortical
      complexity was increased in limbic lobe on bipolar patients. Significant negative
      correlation was also observed between rating scores and asymmetry coefficients in
      frontal lobe.

PMID- 19163574
TI  - Detecting auditory cortex: a comparison of SPM and WSPM.
AB  - Nowadays, statistical parametric mapping (SPM) is the most widely-used method for
      the analysis of fMRI data. As the progress of SPM, some researchers have proposed
      WSPM, a new method based on wavelet transform. The advantage of WSPM is that it
      can not only reduce the spatial bias of SPM, but also shows the closer result to
      the true active areas. In this paper, there are eight sets of fMRI data
      stimulated by voice, from which we want to figure out the active brain areas
      under the stimulation. To confirm the active areas, we used the two methods based
      on different smoothing methods and made comparison. WSPM was showed to have
      stronger control of type-I error (false positives) than SPM.

PMID- 19163575
TI  - Advanced MR diffusion characterization of neural tissue using directional
      diffusion kurtosis analysis.
AB  - MR Diffusion kurtosis imaging (DKI) was proposed recently to study the deviation
      of water diffusion from Gaussian distribution. Mean kurtosis (MK), directionally
      averaged kurtosis, has been shown to be useful in assessing pathophysilogical
      changes. However, MK is not sensitive to kurtosis change occurring along a
      specific direction. Therefore, orthogonal transformation of the 4th order
      kurtosis tensor was introduced in the current study to compute kurtoses along the
      3 eigenvector directions of the 2nd order diffusion tensor. Such axial (K(
      parallel)) and radial (K perpendicular) kurtoses measured the kurtoses along the
      directions parallel and perpendicular, respectively, to the principal diffusion
      direction. DKI experiments were performed in normal adult and formalin-fixed rat
      brain, and developmental brains. The results showed that directional kurtosis
      analysis revealed different information for tissue characterization.

PMID- 19163576
TI  - Adapting population liver motion models for individualized online image-guided
      therapy.
AB  - Respiratory motion varies on a daily basis in abdominal cancer patients,
      affecting the ability to successfully deliver local therapy and requiring
      increased treatment margins to account for this variation. Deformable
      registration techniques can accurately describe respiratory motion, however,
      online application can be limited by long computational times and user
      intervention. A technique has been developed to quickly quantify patient
      breathing motion from respiratory-sorted volumetric images by calculating 1D
      shifts in image intensities between spatially corresponding regions of interest
      (navigator channels) on patient's images. The 1D motion at the superior,
      inferior, anterior, and posterior liver edges was detected and applied to adapt a
      population liver respiratory motion model. For validation, deformable
      registration was performed for each patient using a validated technique, MORFEUS,
      for relative validation, and vessel bifurcations, identified on patient's inhale
      and exhale images, for absolute validation. The accuracy of the adapted
      population model to describe the patient respiratory motion was (absolute mean +/
      SD) 0.26 +/- 0.11 cm and 0.30 +/- 0.21 cm in the superior-inferior (SI) and
      anterior-posterior (AP) directions, respectively. The accuracy of predicting the
      tumor COM motion was 0.30 +/- 0.22 cm, and 0.34 +/- 0.31, while the absolute
      validation, based on bifurcations was 0.26 +/- 0.16 cm and 0.13 +/- 0.04 cm in
      the SI and AP directions, respectively. This technique was developed to
      complement and quickly adapt a full 3D biomechanical based deformable
      registration technique, MORFEUS, to be applied in the online setting.

PMID- 19163577
TI  - Automated 2-D cephalometric analysis of X-ray by image registration approach
      based on least square approximator.
AB  - This paper presents a new approach to cephalometric x-ray landmark localization.
      This approach is based on extracting features from face profile of the lateral
      skull x-ray. The extracted side profile is then segmented based on knowledge of
      known local facial structures. Once the face profile is properly segmented, nine
      perceptually significant landmarks (fiducial points) on the face are registered
      based on a local maximum curvature computation. These fiducial points are used
      for point-by-point correspondence to find the transformation coefficients of the
      control points between two images of a scene. Next, we use the obtained
      coefficients to find the locations of other landmarks on the target image by
      mapping the landmarks of the reference image. The algorithm was tested on more
      than 80 x-ray images to locate 20 landmarks. It was possible to locate the
      landmarks with accuracy of +/-2mm on more 90% of the landmarks.

PMID- 19163578
TI  - Adaptive mesh optimization and nonrigid motion recovery based image registration
      for wide-field-of-view ultrasound imaging.
AB  - Wide field of view (WFOV) imaging mode obtains an ultrasound image over an area
      much larger than the real time window normally available. As the probe is moved
      over the region of interest, new image frames are combined with prior frames to
      form a panorama image. Image registration techniques are used to recover the
      probe motion, eliminating the need for a position sensor. Speckle patterns, which
      are inherent in ultrasound imaging, change, or become decorrelated, as the scan
      plane moves, so we pre-smooth the image to reduce the effects of speckle in
      registration, as well as reducing effects from thermal noise. Because we wish to
      track the movement of features such as structural boundaries, we use an adaptive
      mesh over the entire smoothed image to home in on areas with feature. Motion
      estimation using blocks centered at the individual mesh nodes generates a field
      of motion vectors. After angular correction of motion vectors, we model the
      overall movement between frames as a nonrigid deformation. The polygon filling
      algorithm for precise, persistence-based spatial compounding constructs the final
      speckle reduced WFOV image.

PMID- 19163579
TI  - Mutual information driven inverse consistent nonlinear registration.
AB  - A fully symmetric nonlinear viscoelastic image registration method, under the
      demons paradigm is developed. The symmetric cost function includes mutual
      information (MI) as a similarity measure, regularization of the transformation,
      and inverse consistent constraint (ICC). Alternative strategy is used to minimize
      the divergent terms with different properties in the cost function to avoid the
      difficulties in balancing between the performance of registration and low Inverse
      Consistency Error (ICE). The diffeomorphism of the registration is achieved by
      the composition scheme. Validation studies show that the proposed method provides
      sub-voxel ICE. The improvement of registration performance is also demonstrated.

PMID- 19163580
TI  - Experimental validation of a 4D elastic registration algorithm.
AB  - This paper presents an extensive validation study of an elastic registration
      algorithm for dynamic 3D ultrasound images (also known as a 4D image). The
      registration algorithm uses attribute vectors from both a fixed and previous
      moving images to perform feature-based alignment of a series of images. The 4D
      method reduces computational requirements and increases the effective search
      space for the location of corresponding features, resulting in enhanced
      registration speed when compared to a static 3D registration technique.
      Experimental analysis revealed up to 32% improvement in speed when using the 4D
      method, which makes the algorithm attractive for real-time applications.

PMID- 19163581
TI  - Surface reconstruction from planar x-ray images using moving least squares.
AB  - Planar radiographs still are the gold standard for the measurement of the
      skeletal weight-bearing shape and posture. In this paper, we propose to use an as
      rigid-as-possible deformation approach based on moving least squares to obtain 3D
      personalized bone models from planar x-ray images. Our prototype implementation
      is capable of performing interactive rate shape editing. The biplane
      reconstructions of both femur and vertebrae show a good accuracy when compared to
      CT-scan.

PMID- 19163582
TI  - Non-rigid registration based segmentation of brain subcortical structures using a
      priori knowledge.
AB  - Segmentation of the brain internal structures is an important and a challenging
      task due to their complex shapes, partial volume effects, low contrasts and
      anatomical variability between subjects. In this paper we propose a new non-rigid
      registration method that automatically segments the deep brain internal
      structures from brain MRI images. An atlas of the structures is used as a priori
      knowledge, which is modeled as a shape representation. By integrating the shape
      knowledge into a classical intensity based non-rigid registration algorithm, the
      proposed segmentation method allows to ameliorate the results in the case of low
      contrast on the boundaries of the structures. The shape model is based on
      distance representation obtained from the atlas. The segmentation of brain
      subcortical structures is performed on real MRI images and the obtained results
      are very encouraging.

PMID- 19163583
TI  - 3D multi-modal registration for assessing molecular activity changes in time
      dependent geometries.
AB  - An important issue for in-vivo fluorescence molecular imaging and tomography has
      been the robust registration of animals imaged at different time points in order
      to improve the accuracy of monitoring fluorophore distribution. This paper
      presents a novel automatic method for aligning 3D temporal data of small animals
      based on the robust detection of surface anatomical features. Since it is based
      on 3D surface landmarks the method can be used for mono-modal or multi-modal X
      ray CT and/or Optical tomography data in order to account for differences in the
      positioning and compression of small animals. It can be further extended to other
      imaging modalities, as well.

PMID- 19163584
TI  - Optical flow based volumetric spatio-temporal interpolation.
AB  - Acquisition of three-dimensional medical images with excellent spatial resolution
      is achieved almost always at the cost-dictating expense of increased acquisition
      time. This can be mitigated using shape-respecting inter-slice interpolation of
      sparsely acquired datasets. Existing shape and registration based interpolation
      techniques are suboptimal. This paper proposes a new optical flow based approach
      to interpolate between sparse data. The Horn and Schunck technique is used to
      estimate the pixel-wise flow vectors across the slices; intermediate data planes
      can be reconstructed from these flow vectors. The proposed technique is accurate
      and computationally fast. Coupled with anatomy aware sparse acquisitions, the
      proposed technique shows promise of judiciously managing the patient-specific
      acquisition.

PMID- 19163585
TI  - Estimation of operative line of resection using preoperative image and nonrigid
      registration.
AB  - Even though accurate diagnosis of organs is done using preoperative images such
      as CT or MRI, these information are not directly used in the operating room,
      because organs are nonrigid and their shapes change with time. In this paper, we
      propose to obtain an intraoperative image of an open organ and fuse the image
      with a preoperative image. The intraoperative image is obtained from a three
      dimensional laser scanner. The registration of preoperative image to the
      intraoperative image can relate the information from the preoperative image to
      the open organ in the operating room. We do this by registering preoperative
      images to intraoperative images. An algorithm based on Robust Point Matching
      method is developed for this nonrigid image registration problem. We also propose
      a new metric called Non Overlapping Ratio to determine the registration error.
      The experiments demonstrate that the proposed method is capable of achieving
      region of interest estimation within 1.51 mm mean distance error and 0.66% Non
      Overlapping Ratio.

PMID- 19163586
TI  - Estimation of signal and noise covariance using ICA for high-resolution cortical
      dipole imaging.
AB  - Suitable spatial filters were explored for inverse estimation of cortical dipole
      imaging from a scalp electroencephalogram. Computer simulations were used to
      examine the effects of incorporating statistical information of signal and noise
      into inverse procedures. Actually, the parametric projection filter (PPF) and
      parametric Wiener filter (PWF) were applied to an inhomogeneous three-sphere head
      model. The signal and noise covariance matrices were estimated by applying
      independent component analysis (ICA) to the scalp potentials. The simulation
      results described herein suggest that the PPF using differential noise between
      EEG and separated signal were equivalent to those obtained using the method with
      actual noise. Moreover, the PWF using separated signals has better performance
      than traditional inverse techniques.

PMID- 19163587
TI  - Neuroelectromagnetic forward modeling toolbox.
AB  - This paper introduces a Neuroelectromagnetic Forward Modeling Toolbox running
      under MATLAB (The Mathworks, Inc.) for generating realistic head models from
      available data (MRI and/or electrode locations) and for solving the forward
      problem of electro-magnetic source imaging numerically. The toolbox includes
      tools for segmenting scalp, skull, cerebrospinal fluid (CSF) and brain tissues
      from T1-weighted magnetic resonance (MR) images. After extracting the segmented
      tissue volumes, mesh generation can be performed using deformable models. When MR
      images are not available, it is possible to warp a template head model to
      measured electrode locations to obtain a better-fitting realistic model. The
      Boundary Element Method (BEM) is used for the numerical solution of the forward
      problem. Toolbox functions can be called from either a graphic user interface or
      from the command line. Function help messages and a tutorial are included. The
      toolbox is freely available under the GNU Public License for noncommercial use
      and open source development.

PMID- 19163588
TI  - Community structure of cortical networks in spinal cord injured patients.
AB  - In the present study, we estimated the cortical networks were from high
      resolution EEG recordings in a group of spinal cord injured patients and in a
      group of healthy subjects, during the preparation of a limb movement. Then, we
      use the Markov Clustering method to analyse the division of the network into
      community structures. The results indicate large differences between the injured
      patients and the healthy subjects. In particular, the networks of spinal cord
      injured patient exhibited a higher density of clusters. In the Alpha (7-12 Hz)
      frequency band, the two observed largest communities were mainly composed by the
      cingulate motor areas with the supplementary motor areas, and by the pre-motor
      areas with the right primary motor area of the foot. This functional separation
      could reflect the partial alteration in the primary motor areas because of the
      effects of the spinal cord injury.

PMID- 19163589
TI  - Evoked response denoising using nonlinear diffusion filtering of single-trial
      matrix representations.
AB  - Recent progress in mathematical image processing shows a remarkable success when
      applying numerical methods to ill-posed partial differential equations (PDE). In
      particular, nonlinear diffusion filtering (NDF)process is an approach that
      belongs to such family of differential equations. It has been successfully
      applied in many recent methods for image processing and computer vision areas,
      particularly in denoising, smoothing, segmentation, and restoration. In this
      paper we focus on a novel NDF application, namely denoising of single-trials of
      auditory brainstem responses (ABRs) and the analysis of transcranial magnetic
      stimulation (TMS) responses.We show that by applying NDF on a matrix-form image
      of single-trials, we were able to denoise the single-trials, resulting in a
      better extraction of information over the ongoing experiment; morphology, eg. the
      latency of the single-trials according to different stimuli paradigms at
      different stimulation intensity levels. It is concluded that NDF represents a
      novel and useful approach for the analysis of single-trials in brain imaging.

PMID- 19163590
TI  - 3-D diffusion tensor MRI anisotropy content-adaptive finite element head model
      generation for bioelectromagnetic imaging.
AB  - Realistic finite element (FE) head models have been successfully applied to
      bioelectromagnetic problems due to a realistic representation of arbitrary head
      geometry with inclusion of anisotropic material properties. In this paper, we
      propose a new automatic FE mesh generation scheme to generate a diffusion tensor
      MRI (DT-MRI) white matter anisotropy content-adaptive FE head model. We term this
      kind of mesh as wMesh. With this meshing technique, the anisotropic electrical
      conductivities derived from DT-MRIs can be best incorporated into the model. The
      influence of the white matter anisotropy on the EEG forward solutions has been
      studied via our wMesh head models. The scalp potentials computed from the
      anisotropic wMesh models against those of the isotropic models have been
      compared. The results describe that there are substantial changes in the scalp
      electrical potentials between the isotropic and anisotropic models, indicating
      that the inclusion of the white matter anisotropy is critical for accurate
      computation of E/MEG forward and inverse solutions. This fully automatic
      anisotropy-adaptive wMesh meshing scheme could be useful for modeling of
      individual-specific FE head models with better incorporation of the white matter
      anisotropic property towards bioelectromagnetic imaging.

PMID- 19163591
TI  - Cortical network topology during successful memory encoding in a lifelike
      experiment.
AB  - In the present work, we estimated the functional networks in the frequency domain
      from a set of high-resolution EEG data in a group of healthy subjects during the
      showing of commercial spots within a neutral documentary. Then, we evaluated the
      differences in the cortical network associated with later remembered and not
      remembered commercials by calculating the global- E(g) and local-efficiency E(l)
      indexes. During the visualization of the video-clips that will be forgotten
      (FRG), the cortical network exhibited high values of global- and local
      efficiency, reflecting a small-world configuration. During the visualization of
      the video-clips that will be remembered (RMB), the same indexes appeared
      significantly lower. Such a difference seems not depending on the spectral
      content of the cortical activity. This result shows how the network communication
      efficiency would be affected by the presence of attentional and semantic
      processes that are behind a successful memory encoding in a lifelike situation.

PMID- 19163592
TI  - An optimization based approach embedded in a fuzzy connectivity algorithm for
      airway tree segmentation.
AB  - The main problem with airway segmentation methods which significantly influences
      their accuracy is leakage into the extra-luminal regions due to thinness of the
      airway wall during the process of segmentation. This phenomenon potentially makes
      large regions of lung-parenchyma to be wrongly identified as airways. A solution
      to this problem in the previous methods was based on leak detection followed by
      reducing leakage during the segmentation process. This has been dealt with
      adjusting the segmentation parameters and performing the re-segmentation process
      on the pre-segmented area. This makes the algorithm very exhaustive and more
      dependent on the user interaction. The method presented here is to apply a
      mathematical shape optimization approach embedded in an efficient fuzzy
      connectivity based segmentation algorithm to preserve shape features of the
      object to perform a precise segmentation. The novelty of our proposed scheme is
      to prevent the leakage root rather than taking leak detection and reduction
      approaches. This is carried out by minimizing a gradient based cost function
      which employs shape features of circle/cylindrical structure of airway tree
      during the process of segmentation.

PMID- 19163593
TI  - An improved spatial tracking algorithm applied to coronary veins into Cardiac
      Multi-Slice Computed Tomography volume.
AB  - This paper describes an enhanced vessel tracking algorithm. The method specifity
      relies on the coronary venous tree extraction through Cardiac Multi-Slice
      Computed Tomography (MSCT). Indeed, contrast inhomogeneities are a major issue in
      the data sets that necessitate a robust tracking procedure. The method is based
      on an existing moment-based algorithm designed for coronary arteries into MSCT
      volume. In order to extract the whole path of interest, improvements concerning
      progression strategy are proposed. Furthermore, the original procedure is
      combined with an automatic recentring method based on ray casting. This enhanced
      method has been tested on three data sets. According to the first results, the
      method appears robust to curvatures, contrast inhomogeneities and low contrast
      blood veins.

PMID- 19163594
TI  - Efficient large scale image stitching for virtual microscopy.
AB  - We describe a weighted least squares based global registration method for
      creating virtual slides. In microscopy a large number of fields of view is
      required to capture a complete slide. These fields of view are aligned in such a
      way that a globally consistent virtual slide is formed. The positioning accuracy
      of the presented algorithm is evaluated using a new method based on synthetic
      virtual slides. Using these synthetic virtual slides it is now possible to give a
      ground truth about the positioning accuracy of stitching algorithm for virtual
      microscopy. Our algorithm has been evaluated on these synthetic slides and it can
      be shown that on average, each image exhibits a mean deviation of 0.8 pixel with
      respect to the correct position. Additionally the presented algorithm has been
      evaluated on several real world examples.

PMID- 19163595
TI  - Activation of the prefrontal cortex during a visual n-back working memory task
      with varying memory load: a near infrared spectroscopy study.
AB  - We evaluated frontal brain activation during a Working Memory task with graded
      levels of difficulty in a group of 15 healthy subjects, by means of fNIRS
      technique. Brain activation (% signal change with respect to the baseline) was
      computed and load-related increases of blood oxygenation were found for the four
      different levels of task difficulty. Generalized Linear Models were applied to
      the data in order to evaluate the metabolic processes occurring during the mental
      effort and, possibly, their involvement in short term memorization. The Cognitive
      Failure Questionnaire was also administered in order to assess its diagnostic
      relevance in clinics. Results attest a monotous increase of brain oxygenation
      with WM load during the first half of task, persisting through the central
      resting period and prevailing in the left hemisphere. Decreasing WM load is also
      coupled with oxygenated hemoglobin decrease.

PMID- 19163596
TI  - The impact of ablated cortex on the validity and interpretation of the fNIRS
      signal.
AB  - Functional near infrared spectroscopy (fNIRS) is a safe and portable brain
      imaging modality that monitors changes in the hemodynamic activity at the
      cortical level. Although still in its emerging stage, fNIRS has recently gained
      increasing acknowledgements of its strengths and suitability for many clinical
      applications. The fast evolution and growth of fNIRS applications has been made
      possible mainly by studies that substantiate the general validity of the fNIRS
      measures. Such studies investigate both the fNIRS construct, by cross-validating
      it with fMRI, and the repeatability of fNIRS measures.Nonetheless, cases exist
      that would pose a challenge forfNIRS measures of cortical activation. In
      particular, violations of the assumptions made on the optical properties of the
      sampled tissue would affect some variables included in the modified Beer-Lambert
      law (mBBL), which allows conversion of the changes in measured light intensity
      into changes in the oxyhemoglobin and deoxyhemoglobin concentrations. These
      violations would therefore reflect on the fNIRS readings and on the way data are
      interpreted. The aim of this paper is to present an example of such challenging
      situations. The case presented is a subject whose left frontal lobe cortex has
      been partially ablated following a subdural hematoma. fNIRS measures were
      recorded during a verbal fluency task, known to be associated to functioning of
      the left frontal lobe. We examine the outcome of fNIRS, contextualizing it in the
      framework of the mBLL and its assumptions.

PMID- 19163597
TI  - Digital photographic imaging system for the evaluation of various facial skin
      lesions.
AB  - In dermatology, various imaging modalities have been developed as an assistant
      tool to objectively evaluate the treatment efficacy of facial skin lesion. In
      this study, we propose a digital photographic imaging system the evaluation of
      various facial skin lesions in order to maximize the clinical evaluation
      efficiency by integrating various independent imaging modalities. Our imaging
      system provides four different digital color images, such as standard digital
      color image, parallel and cross polarization digital color image, and UV-A
      induced fluorescent digital color image. In conclusion, by analyzing the color
      information and morphological features, we were able to simultaneously evaluate
      various skin lesions with one imaging system.

PMID- 19163598
TI  - A feedback retina model for improving medical images fusion.
AB  - Image fusion has become a powerful technique for increasing the interpretation
      quality of images in medical applications. The diagnostic potential of brain
      positron emission tomography (PET) imaging is limited by low spatial resolution.
      For solving this problem, the high-frequency part of the MRI, which would be
      unrecoverable by the set PET acquisition system, is extracted and added to the
      PET image. The procedure has the potential of increasing the diagnostic value of
      a PET image. This paper presents a feedback retina model technique to reduce the
      spectral distortion and preserve high spatial resolution. Visual and statistical
      analyses show that the proposed feedback retina model significantly improves the
      fusion quality compared to non-feedback retina model.

PMID- 19163599
TI  - Medical image segmentation using watershed segmentation with texture-based region
      merging.
AB  - The use of the watershed algorithm for image segmentation is widespread because
      it is able to produce a complete division of the image. However, it is
      susceptible to over-segmentation and in medical image segmentation, this meant
      that that we do not have good representations of the anatomy. We address this
      issue by thresholding the gradient magnitude image and performing post
      segmentation merging on the initial segmentation map. The automated thresholding
      technique is based on the histogram of the gradient magnitude map while the post
      segmentation merging is based on the similarity in textural features (namely
      angular second moment, contrast, entropy and inverse difference moment) belonging
      to two neighboring partitions. When applied to the segmentation of various facial
      anatomical structures from magnetic resonance (MR) images, the proposed method
      achieved an overlap index of 92.6% compared to manual contour tracings. It is
      able to merge more than 80% of the initial partitions, which indicates that a
      large amount of over-segmentation has been reduced. Results produced using
      watershed algorithm with and without the proposed and proposed post-segmentation
      merging are presented for comparisons.

PMID- 19163600
TI  - Unwrapping MR phase maps with Chebyshev moments.
AB  - Previous polynomial model based phase unwrapping algorithms relied on least
      squares fitting to determine the polynomial coefficients. This work presents a
      phase unwrapping algorithm, based on the method of moments, and calculates the
      polynomial coefficients using integration. The phase unwrapping algorithm is
      developed using Chebyshev polynomials. The phase unwrapping algorithm implemented
      in this work is tested on 2-D phase maps obtained from a 3 Tesla magnetic
      resonance scanner. In this work, the effectiveness of the phase unwrapping
      algorithm on MR phase maps is investigated.

PMID- 19163601
TI  - Assessment of depth and degeneration dependences of articular cartilage
      refractive index using optical coherence tomography in vitro.
AB  - Measuring the depth and degeneration dependences of articular cartilage is
      important for the investigation of cartilage structure and the reason behind its
      degeneration. In this study, optical coherence tomography (OCT) was used to
      investigate the depth and degeneration dependences of the refractive index (RI)
      of articular cartilage collected from bovine patellae in vitro. Eighteen disks of
      articular cartilage with a diameter of 6.35 mm harvested from different patellae
      were prepared. Each disk was cut into two halves and three horizontal cartilage
      slices (n=18 x 2 x 3) with approximately equal thickness were further prepared
      from each half disk. The cartilage slices were digested by two different enzymes,
      collagenase and trypsin, to remove collagen fibres and proteoglycans,
      respectively. The samples were tested using OCT before and after the enzyme
      digestion and the RI for each specimen was calculated. Two-factor repeated
      measure ANOVA showed that for all the three groups of specimens, the RI in
      different depths was significantly different (p0.05). However, it was revealed
      that the trypsin and collagenase treatments did not exert a significant effect on
      the RI (p0.05). The results suggested that the depth dependence of articular
      cartilage should be taken into account when OCT is used for related measurement.

PMID- 19163602
TI  - Detection of subgingival calculus through oral gum in vitro using two-photon
      fluorescence microscopy.
AB  - Periodontal disease is one of the main chronic infectious diseases of oral cavity
      and the principal cause of tooth loss in humans. The main cause of periodontal
      disease is the bacteria in calculus or plaque to cause the gum inflamed.
      Therefore detection and removal of subgingival calculus remains important to all
      periodontal therapy. However, subgingival calculus within the periodontal pocket
      remains a complicated and potentially delicate structure to be detected and
      treated with current dental armamentaria, namely dental x-rays and the dental
      probe. In this study, an innovative subgingival calculus detection system
      employing autofluorescence imaging has been developed. Feasibility of such a
      system on the detection of subgingival calculus is investigated in vitro.
      Autofluorescence imaging is based on two-photon time correlated fluorescence
      technique by a femtosecond pulsed Ti-sapphire laser.

PMID- 19163603
TI  - Detection of suspicious pain regions on a digital infrared thermal image using
      the multimodal function optimization.
AB  - Automatic detection of suspicious pain regions is very useful in the medical
      digital infrared thermal imaging research area. To detect those regions, we use
      the SOFES (Survival Of the Fitness kind of the Evolution Strategy) algorithm
      which is one of the multimodal function optimization methods. We apply this
      algorithm to famous diseases, such as a foot of the glycosuria, the degenerative
      arthritis and the varicose vein. The SOFES algorithm is available to detect some
      hot spots or warm lines as veins. And according to a hundred of trials, the
      algorithm is very fast to converge.

PMID- 19163604
TI  - The image feature analysis for microscopic thyroid tissue classification.
AB  - Thyroid diseases are prevalent among endocrine diseases. Observation and
      examination of histological tissue images can help in understanding the cause and
      pathogenesis of the tumor. The aim of this study was to quantify the histological
      image features of microscopic thyroid images in order to classify varying tissue
      types. Five typical histological thyroid tissues were characterized using seven
      image features including hue, brightness, standard deviation of brightness,
      entropy, energy, regularity, and fractal analysis. Statistical stepwise selection
      and multiple discriminant analysis were then used to classify the features. The
      results show all of the features are significant and our algorithm has the
      capability of differentiating histological tissue types. The algorithm is applied
      utilizing quad-tree based region splitting methods to segment the tissue regions
      from the heterogeneous microscopic image. The preliminary results show the system
      has good performance for tissue segmentation.

PMID- 19163605
TI  - A Bayesian hierarchical model for classifying craniofacial malformations from CT
      imaging.
AB  - Single-suture craniosynostosis is a condition of the sutures of the infant's
      skull that causes major craniofacial deformities and is associated with an
      increased risk of cognitive deficits and learning/language disabilities. In this
      paper we adapt to classification of synostostic head shapes a Bayesian
      methodology that overcomes the limitations of our previously published shape
      representation and classification techniques. We evaluate our approach in a
      series of large-scale experiments and show performance superior to those of
      standard approaches such as Fourier descriptors, cranial spectrum, and Euclidian
      distance-based analyses.

PMID- 19163606
TI  - Objective assessment of psoriasis erythema for PASI scoring.
AB  - Skin colour is vital information in dermatological diagnosis. It reflects
      pathological condition beneath the skin and commonly being used to indicate the
      extent of a disease. Psoriasis is a skin disease which is indicated by the
      appearance of red plaques. Although there is no cure for psoriasis, there are
      many treatment modalities to help control the disease. To evaluate treatment
      efficacy, PASI (Psoriasis Area and Severity Index) which is the current gold
      standard method is used to determine severity of psoriasis lesion. Erythema
      (redness) is one parameter in PASI. Commonly, the erythema is assessed visually,
      thus leading to subjective and inconsistent result. In this work, we proposed an
      objective assessment of psoriasis erythema for PASI scoring. The colour of
      psoriasis lesion is analyzed by DeltaL, Deltahue, and Deltachroma of CIELAB
      colour space. References of lesion with different scores are obtained from the
      selected lesions by two dermatologists. Results based on 38 lesions from 22
      patients with various level of skin pigmentation show that PASI erythema score
      can be determined objectively and consistent with dermatology scoring.

PMID- 19163607
TI  - Automatic working area classification in peripheral blood smears without cell
      central zone extraction.
AB  - In this paper we study automatic classification of working areas in peripheral
      blood smears using image analysis and recognition methods. Such automatic
      classification can provide objective and reproducible quality control for the
      evaluation of smears and smear maker devices. However, research in this filed has
      drawn little attention. Existing methods either can not differentiate correctly
      different cell distributions or rely on the extraction of the central pallor
      zones in cells for counting, which are not always observable. In contrast, we do
      not rely on the pallor zone extraction thus on more general basis. We introduce
      two generic parameters to measure the goodness of working areas, one for the
      degree of overlap, and the other for the spatial occupancy. We also propose a
      cascading classification network for the classification of different areas. The
      effectiveness of our method has been tested on over 150 labeled images acquired
      from three malaria-infected Giemsa-stained blood smears using an oil immersion
      100 x objective.

PMID- 19163608
TI  - Extraction of acne lesion in acne patients from multispectral images.
AB  - In acne treatment, it is important to accurately evaluate the severity of Acne.
      The acne should be classified into several skin lesions including comedo, reddish
      papule, pustule, and scar. However, in some cases, a visual detection from RGB
      image maybe difficult for the proper evaluation of acne skin lesions. This paper
      proposes an extraction method using the spectral information of the various type
      of acne skin lesions calculated from the multispectral images (MSI) of the
      lesions. In the experiment, we showed the possibility of classifying acne lesion
      types by applying a combination of several linear discriminant functions (LDF's).

PMID- 19163609
TI  - Classifying the motion of visual stimuli from the spike response of a population
      of retinal ganglion cells.
AB  - We present an analysis of the spike response of a retinal ganglion cell ensemble.
      The retina of a turtle was stimulated in vitro by moving light patterns. Its non
      steady motion was specified by two features: changes of direction and changes of
      speed. The spike response of a ganglion cell population was recorded
      extracellularly with a multielectrode array and responding neurons were
      identified through spike sorting. Restricting further analysis to a time window
      of greatest firing activity, we selected a subset of cells with reliable firing
      patterns, excluding cells that were not selective to the stimulus. The
      reliability of a firing pattern was assessed on the single cell level in terms of
      two measures: temporal precision (jitter) of the first spike and the fraction of
      trials in which a spike was generated. We then condensed the spike response of
      the extracted group by merging the multivariate spike trains into a single spike
      train. Finally, we compared different coding hypotheses that are based on the
      timing of the first and the second spike of the population or the spike count in
      the preselected time window. We found that the second spike of the population
      significantly increases the classification efficiency beyond that of the first
      spike. Moreover, the combination of first plus second spike is comparably
      efficient as the combination of the first spike plus the spike count but allows
      for a classification that is much faster.

PMID- 19163610
TI  - A system for exploring and visualizing biological pathways from large scale
      datasets.
AB  - The growing accumulation of biological pathway datasets is making it possible to
      study pathways at genomic scale by exploration and visualization, facilitating
      the shift of biomedical research to systems-level analyses. Presented in this
      paper is our ongoing work on developing a system for exploring and visualizing
      biological pathways for large scale pathway analyses. A pathway repository with a
      standard data format was developed for storing various types of pathways,
      mechanisms for navigating among different pathway datasets and to external data
      sources were also designed, and a rendering engine is being developed to allow
      user for visualization and exploration.

PMID- 19163611
TI  - 3-D finite element analysis on brain injury mechanism.
AB  - The purpose of this study is to discuss the mechanism of brain injury
      analytically by a cavitation phenomenon. Cavitation damage is assumed to be one
      of the causes brain injury. Performing the computer simulation of brain injury,
      it is not easy to incorporate the term of a cavitation occurrence in a governing
      equation. Therefore, we predict the cavitation occurrence from the results of
      stress, pressure, and displacement of the analytical model by FEM. Here,
      comparing frequency and pressure changes, we discussed the basic mechanism of
      brain injury analytically. First, a three-dimensional FEM model for impact
      analysis was presented. The high-pressure changes generated in the acrylic
      container at the time of impact were transmitted through this container, and the
      positive maximum pressure change was caused at the contrecoup side. Second, the
      results of the frequency analysis of pressure changes by a FFT were presented. We
      found spectrums in some frequency bands, which seemed to be the occurrence of the
      brain injury. From these results, it was found that the computer simulation
      methods were useful to predict the occurrence mechanism of contrecoup injury.

PMID- 19163612
TI  - Multi-class alignment of LC-MS data using probabilistic-based mixture regression
      models.
AB  - In this paper, a framework of probabilistic-based mixture regression models
      (PMRM) is presented for multi-class alignment of liquid chromatography-mass
      spectrometry (LC-MS) data. The proposed framework performs the alignment in both
      time and measurement spaces of the LC-MS spectra. The expectation maximization
      (EM) algorithm is used to estimate the joint parameters of spline-based mixture
      regression models and prior transformation densities. The latter are incorporated
      to account for variability in time and measurement spaces of the data. As a proof
      of concept, the proposed method is applied to align a single-class replicate LC
      MS spectra generated from proteins of lysed E.coli cells. Its performance is
      compared with the dynamic time warping (DTW) and continuous profile model (CPM)
      approaches.

PMID- 19163613
TI  - In silico screening of Rac1 ligand specificity.
AB  - Microtubule (MT) destabilization promotes the formation of actin stress fibers
      and enhances the contractility of cells. The actin cytoskeleton is bound to each
      junction and controls the integrity of each through actin remodeling and these
      junctions can be disassembled or assembled to either increase or decrease
      cellular permeability. Mediators, such as thrombin, stimulate their respective
      receptor on endothelial cells to initiate signaling that increases cytosolic Ca2+
      and activates myosin light chain kinase (MLCK), as well as monomeric GTPases
      RhoA, Rac1, and Cdc42. Ca2+ activation of MLCK and RhoA disrupts junctions,
      whereas Rac1 and Cdc42 promote junctional assembly. In order to develop formal
      systems biology model of actin remodelling it is necessary to investigate the
      reciprocal interactions between Rac1 and Cdc42 by using experimental selective
      inhibition. We have screened, by docking analysis, a new class of compounds for
      Rac1 and/or Cdc42 inhibition, the Morpholinos, that could be used as alternative
      tool to switch off a gene.

PMID- 19163614
TI  - A cluster-aware graphical user interface for a virtual ligand screening tool.
AB  - In this paper, we describe the design and implementation of a Graphical User
      Interface (GUI) for Cassandra, a computer application for Virtual Ligand
      Screening (VLS). The GUI was designed using Trolltech QT4 and Perl, and serves
      the purpose of making the execution of Cassandra more user-friendly. Through this
      GUI, users can manage multiple concurrent, interactive data paths both on a
      single machine and on a High Performance Computing Cluster (HPCC). The GUI
      successfully decreased the complexity and steep learning curve of using
      Cassandra, and the average time to execute a VLS project. As result, we reduced
      the time necessary to train new users, increased the number of users, increased
      the overall efficiency of Cassandra, and optimized data handling and analysis.

PMID- 19163615
TI  - Fractal dimension and wavelet decomposition for robust microarray data
      clustering.
AB  - Microarrays are now established technologies which are considered as key to gene
      expression analysis. Their study is usually achieved by using clustering
      techniques. Genomic signal processing is a new area of research that combines
      genomics with digital signal processing methodologies. In this paper, we present
      a comparative analysis of two genomic signal processing methods for robust
      microarray data clustering. Techniques based on Fractal Dimension and Discrete
      Wavelet Decomposition with Vector Quantization are validated for standard data
      sets. Comparative analysis of the results indicates that these methods provide
      improved clustering accuracy compared to some conventional clustering techniques.
      Moreover, these classifiers don't require any prior training procedures.

PMID- 19163616
TI  - Complexity evolution in epileptic seizure.
AB  - The present paper concentrates on neural complexity generated during the phase
      transition in epileptic seizure. Epileptic seizures represent a sudden and
      transient change in the synchronized firing of neuronal brain ensembles. The
      proposed model treats the brain as an excitable medium for the propagation of
      waves of electrical activity with a level of abstraction encompassing underlying
      variables into a number of discrete states. The analysis presented here provides
      support for the notion of dynamical phase transition in the sequence of chaos -->
      complexity --> order during the progress of epilepsy. Evolving cellular automata
      and quantifying it using Langton parameter shows critical value or highest
      complexity at the onset of seizure phenomenon.

PMID- 19163617
TI  - The time-frequency representation of the ERPs of face processing.
AB  - In ERP studies of face processing, N170 and VPP were considered to reflect the
      structural encoding of faces in many researches. However, whether the VPP is the
      positive counterpart of the N170 from the same brain source is still a matter of
      debate. In present study, in order to address the debate we studied the
      oscillatory activities of event-related potentials (ERPs) during face processing.
      We recorded the ERPs in response to upright and inverted faces, and analyzed the
      time-frequency representation (TFR) by using the Smoothed Pseudo Wigner-Ville
      Distribution (SPWVD). The TFR of ERPs suggests that the oscillations at occipito
      temporal sites (T5/T6) where the N170 was observed, were centralized in a higher
      frequency band (4-10 Hz) while the oscillations at the fronto-central site (Cz)
      with salient VPP, were more centralized in a lower frequency range(0-5 Hz).
      Therefore, we concluded that the face-sensitive N170 and VPP, associated with
      'the structural encoding' stage of the face processing in Bruce & Young's model,
      reflect the activities from two different sources. Furthermore, different
      oscillatory activities were obtained at different face processing stages: 0-10 Hz
      oscillations around 100-200 ms post-stimulus are involved in face encoding
      processing, 0-4 Hz oscillations around 300-400 ms post-stimulus are involved in
      the later face identification and the enhanced activities in response to the
      inverted faces indicate a higher number of synchronous neuronal populations.

PMID- 19163618
TI  - Non-target photo images in oddball paradigm improve EEG-based personal
      identification rates.
AB  - A research on biometry based on human brain activities has lately been emerging.
      In this study, we investigate the feasibility of personal identification using
      one-channel electroencephalogram during photo retrieval in oddball paradigm. The
      use of non-target photo images was examined to improve the identification
      performances. Nine photo images were randomly presented one after another to five
      subjects. The Principal Component Analysis and the Linear Discriminant Analysis
      were applied for the signal processing. With EEG activities both during target
      and non-target photo retrieval, the algorithm successfully improved the
      identification rates. The rates were 87.2, 95.0, and 97.6% using 5, 10, and 20
      time averaging, respectively. The performances with EEG only during target photo
      retrieval were lower by 5-13%. This study reveals a future possibility of photo
      retrieval tasks to realize the personal identification using human brain
      activities, which will yield rich controls of machine for the users of brain
      computer-interface.

PMID- 19163619
TI  - Functional-MRI correlates of cued slow-eye-closure and task non-responsiveness
      during visuomotor tracking.
AB  - Slow-eye-closure and task non-responsiveness are important behavioural markers of
      microsleeps. This paper presents preliminary results on the neural correlates of
      voluntary slow-eye-closure and voluntary non-responsiveness during performance of
      a continuous visuomotor tracking task. Functional-MRI (fMRI), EEG, eye video, and
      tracking responses were recorded from 5 normal subjects while they performed a
      continuous visuomotor tracking task inside an MRI scanner for 10 min. During this
      time, they were cued to simultaneously stop tracking and slowly close their eyes
      or stop tracking without eye-closure several times. Analysis of fMRI data
      revealed several regions involved in cued slow-eye-closure and cued task non
      responsiveness, including occipito-parietal visual regions, midline default mode
      regions, and fronto-parietal attention regions. These results will be of
      considerable value in the interpretation of changes in BOLD activation and EEG
      activity associated with behavioural microsleeps.

PMID- 19163620
TI  - Measurement of evoked potential in recognition of faces and buildings.
AB  - In the functional neuro-imaging, it is known that the activation to the second
      stimulus is suppressed when two stimuli are given successively with a short
      interval as sensory inputs. This kind of suppressive phenomenon has been observed
      in event-related potential (ERP) signals as well as functional MRI signals of
      primary auditory, somatosensory and visual cortices. However, we rarely find
      reports to ERP suppression in higher-order areas of the brain. In this study we
      used a paired stimulus paradigm. The paired stimulus paradigm consisted of
      successively presented two stimuli in one trial. We recorded ERP related to
      recognition of faces and buildings to investigate the suppressive phenomenon in
      higher-order areas of the brain. We used the paired stimulus paradigm which was
      comprised of face, building and gray-colored-plain (gray) pictures. The inter
      stimulus interval of two stimuli was 200 ms. On the points of O2 and T6, we
      observed that the ERP for the latter stimulus (face picture) was suppressed
      severely when a face-gray stimulus pair was presented. On the other hand, when a
      gray-building stimulus pair was presented, the ERP for the latter stimulus
      (building picture) was not suppressed on the points of O2 and T6. The similar
      suppression was observed with a face-face stimulus pair.

PMID- 19163621
TI  - Measurements of the micro/beta ERD and gamma ERS during the imagination of body
      parts movement.
AB  - In recent years, many studies shows that the ERS (event-related synchronization)
      in the gamma band is associated with cortical activation during the imagination
      of body parts movement. It is also known that the ERD (event-related
      desynchronization) in the micro and beta band are caused by the imagination of
      body parts movement. In this study, we investigated the relationship between the
      gamma ERS and micro/beta ERDs. We recorded 64-channel EEG in order to obtain the
      power map of the gamma component. Furthermore, we compared the characteristics of
      the gamma waveform and micro/beta waveforms at the locations where the gamma ERS
      appeared clearly. As a result, we obtained three conclusions. Firstly, gamma ERS
      caused by the imagination of body parts movement appears at near somatosensory
      area and motor area. Gamma ERS caused by the imagination of right arm movement
      appears at the left side of the somatosensory area, that of left arm movement
      appears at the right side of the somatosensory area, and that of the foot
      movement appears at the center of the motor area. Secondly, micro/beta ERDs
      appear simultaneously with the preparation of the imagination, and they continue
      during the imagination. However, gamma ERS appeared simultaneously with the
      imagination of body parts movement. Finally, the power of the micro/beta
      component decrease gradually, but that of the gamma component increases
      significantly.

PMID- 19163622
TI  - The effects of interictal spikes on single neuron firing patterns in the
      hippocampus during the development of temporal lobe epilepsy.
AB  - The interictal spikes (IS) are characteristic signatures of epileptic tissue, and
      relevant in presurgical evaluation of epilepsy. However, the mechanism and
      effects of IS remain unclear. In this study, we examined the relationship between
      IS and single neuron firing patterns, using an epileptic rat with temporal lobe
      epilepsy (TLE). We investigated the firing of interneurons and pyramidal cells in
      the CA3 region of the hippocampus. The results show that IS are associated with
      decreased single neuron firing rates compared with IS-free epochs. Furthermore,
      the paroxysmal interictal-spiking patterns are associated with sustained decrease
      in single neuron firing rates. We also found that IS stopped as approaching to
      seizures. These results demonstrate that IS might be responsible for the
      development of TLE and ictal events by changing the firing patterns of
      hippocampal neurons.

PMID- 19163623
TI  - Using motor unit potential characterizations to estimate neuromuscular disorder
      level of involvement.
AB  - Based on the analysis of electromyographic (EMG) data muscles are often
      characterized as normal or affected by a neuromuscular disorder. Motor unit
      potential (MUP) characterizations comprised of the conditional probabilities of a
      MUP being detected from a muscle of each of the following categories: myopathic,
      normal, and neuropathic, were estimated. The sets of MUP characterizations of a
      set of MUPs detected in a muscle were averaged to produce a set of muscle
      characterization measures related to the probability of the muscle belonging to
      each category conditioned on the set of MUPs detected. Using simulated EMG
      signals, the objective of this work was to evaluate the correlation between the
      muscle characterization measures produced by different MUP characterization
      methods and the level of involvement of a disorder. The results showed a
      correlation of 0.9 between myopathic and neuropathic muscle characterization
      measures and the actual level of involvement when using a Pattern Discovery (PD)
      method to estimate MUP characterizations. This work suggests that MUP
      characterizations can be used to assist clinicians in tracking the progress of a
      disease process.

PMID- 19163624
TI  - EVestG: a diagnostic measure for schizophrenia.
AB  - Schizophrenia is a severe mental illness associated with multiple
      neuropathological, neurochemical and genetic abnormalities. The benefits of a
      validated, quantitative diagnosis tool are well established.
      Electrovestibulography, a new method similar to ECOG, can detect and record
      neural activity generated by the vestibular system. The normal EVestG response as
      well as dynamic measures averaged 'background-onAA' (onAA=acceleration phase of
      tilt) and 'background-onBB' (onBB=deceleration phase of tilt) of excitatory (ipsi
      lateral tilt) vestibular responses are compared for a small group of
      schizophrenia patients (n=4) and age matched healthy controls (n=10). Our
      preliminary results show an apparent discrimination between control and
      schizophrenia groups. Schizophrenia patients appear not only to exhibit an
      overall decreased EVestG signal amplitude but a suppressed dynamic response
      calculated by the averaged EVestG 'background-onBB' measure. Increased sample
      size is required to validate these findings.

PMID- 19163625
TI  - Electrophysiologic studies of neronal activities under ischemia condition.
AB  - Substrate with integrated microelectrode arrays (MEAs) provides an alternative
      electrophysiological method. With MEAS, one can measure the impedance and elicit
      electrical stimulation from multiple sites of MEAs to determine the
      electrophysiological conditions of cells. The aims of this research were to
      construct an impedance and action potential measurement system for neurons
      cultured on MEAs for observing the electrophysiological signal transmission in
      neuronal network during glucose and oxygen deprivation (OGD). An extracellular
      stimulator producing the biphasic micro-current pulse for neuron stimulation was
      built in this study. From the time-course recording of impedance, OGD condition
      effectively induced damage in neurons in vitro. It is known that the results of
      cell stimulation are affected by electrode impedance, so does the result of
      neuron cells covered on the electrode can measure the sealing resistance. For
      extracellular stimulation study, cortical neuronal activity was recorded and the
      suitable stimulation window was determined. However, the stimulation results were
      affected by electrode impedance as well as sealing impedance resulting from
      neuron cells covering the electrode. Further development of surface modification
      for cultured neuron network should provide a better way for in vitro impedance
      and electrophysiological measurements.

PMID- 19163626
TI  - A portable, low-cost assessment device for reaching times.
AB  - We present the Systematic Test for Assessing Reaching Times (START), an
      interactive device for measuring reaction and movement times. START uses randomly
      lighted buttons to elicit reaches to a variety of target locations with a
      standardized setup. A magnetized wristband and reed switch monitor the hand rest
      position while capacitive touch sensors embedded in the buttons sense successful
      target reaches. A microcontroller measures reaching times at tens of milliseconds
      resolution. START can easily translate to the clinic because it is portable, easy
      to use and inexpensive to construct. We designed START for use with stroke
      patients and are using START to assess the progress of upper extremity
      rehabilitation of stroke survivors. It can be modified to fit a number of other
      motor control or cognitive tasks.

PMID- 19163627
TI  - Unintentional balance destabilization system reliability studies.
AB  - The extent of neural and muscular response differences to sudden unintentional
      balance destabilization system (UBDS) compared to command-driven tasks could
      produce a new measure to explain why some elders who do well in command-driven
      clinical balance tests experience unintentional falls. This paper presents pilot
      studies on the reliability that UBDS test environment compared to performing
      command-driven tasks triggers a characteristic trend in neural and muscular
      response latencies in humans. Eleven adults 60 years or older participated in
      this study. Tasks performed included maintaining balance while balance is
      suddenly perturbed by the UBDS and while performing command-driven sit-to-stand
      and stand-to- sit tasks. Signals were synchronously recorded from the forehead,
      the neck and 6 muscle groups of both legs. Each subject visited the lab the
      following day for repeat test. One way ANOVA was used to determine the main
      differences in neural and muscular response latencies between repeat trials
      during both UBDS and command-driven test scenarios.Graphical analysis was also
      used to elucidate latency trend between test-retest trials.Test results show
      consistent significant prolonged response latency differences when
      destabilization is caused by UBDS test environment than while performing any of
      the command-driven tests. Within each test scenario for UBDS at 95% confidence
      interval test-retest p value for latency variable was less than 0.000001 except
      for one person, for both command-driven tasks there were no significant latency
      differences, at 95% confidence intervals p values were greater than 0.8 except
      for one at 001.The trends were depicted graphically also.The results demonstrated
      test-retest reliability thatUBDS triggers prolonged response latency when balance
      is suddenly perturbed, a variable that is not detectable during command-driven
      tests.

PMID- 19163628
TI  - On the synthesis of multiple frequency tone burst stimuli for efficient high
      frequency auditory brainstem response.
AB  - The development and digital waveform synthesis of a multiple-frequency tone-burst
      (MFTB) stimulus is presented. The stimulus is designed to improve the efficiency
      of monitoring high-frequency auditory-brainstem-response (ABR) hearing
      thresholds. The pure-tone-based, fractional-octave-bandwidth MFTB supports
      frequency selective ABR audiometry with a bandwidth that falls between the
      conventional click and single-frequency tone-burst stimuli. The MFTB is being
      used to identify high frequency hearing threshold change due to ototoxic
      medication which most generally starts at the ultra-highest hearing frequencies
      and progresses downwards but could be useful in general limited-bandwidth testing
      applications. Included is a Mathcad implementation and analysis of our MFTB
      synthesis technique and sample performance measurements of the MFTB stimulus
      configuration used in a clinical research ABR system.

PMID- 19163629
TI  - EVestG: a measure for Meniere's Disease.
AB  - Meniere's Disease is commonly diagnosed using Electrocochleography (ECOG). EVestG
      is a variant of ECOG utilizing one or more patient tilts as stimuli in place of
      the ECOG's repeated tonal clicks. The dynamic measures averaged 'background-onAA'
      (onAA=acceleration phase of tilt) and background-onBB (onBB=deceleration phase of
      tilt) of excitatory (ipsilateral tilt) vestibular responses are compared for a
      small group of age matched Controls (n=18) and Meniere's Disease patients (n=11).
      Preliminary data provides for an apparent clearer demarcation between Controls
      and Meniere's patients. Meniere's patients appear to show not only increased
      Sp/Ap ratios but also a decreased dynamic range of response as measured by the
      EVestG response measure averaged 'background-onBB'. Increased sample size is
      required to validate these findings.

PMID- 19163630
TI  - On the single sweep processing of auditory brainstem responses: click vs. chirp
      stimulations and active vs. passive electrodes.
AB  - We have recently shown that click evoked auditory brainstem responses (ABRs)
      single sweeps can efficiently be processed by a hybrid novelty detection system.
      This approach allowed for the objective detection of hearing thresholds in a
      fraction of time of conventional schemes, making it appropriate for the efficient
      implementation of newborn hearing screening procedures. It is the objective of
      this study to evaluate whether this approach might further be improved by
      different stimulation paradigms and electrode settings. In particular, we
      evaluate chirp stimulations which compensate the basilar-membrane dispersion and
      active electrodes which are less sensitive to movements. This is the first study
      which is directed to a single sweep processing of chirp evoked ABRs. By
      concentrating on transparent features and a minimum number of adjustable
      parameters, we present an objective comparison of click vs.chirp stimulations and
      active vs. passive electrodes in the ultrafast ABR detection. We show that chirp
      evoked brainstem responses and active electrodes might improve the single sweeps
      analysis of ABRs.Consequently, we conclude that a single sweep processing of ABRs
      for the objective determination of hearing thresholds can further be improved by
      the use of optimized chirp stimulations and active electrodes.

PMID- 19163631
TI  - Effect of grip location, arm support, and muscle stretch on sustained finger
      flexor activity following stroke.
AB  - After gripping an object with the affected hand, stroke survivors may experience
      difficulty in relaxing the hand to release the object. The goals of this study
      were: 1) to quantify the severity of this problem by measuring the time needed to
      terminate a grip activity (grip termination time) and 2) to examine the effect of
      factors such as grip location, external arm support, and muscle stretch on grip
      termination time for the affected hand. Ten subjects with chronic hemiparesis
      subsequent to stroke grasped a cylinder with maximum effort for 5 seconds and
      then attempted to relax the fingers as quickly as possible. Finger flexor muscle
      activity was recorded. Grip termination time was defined as the time required for
      the finger flexor activity to drop to the initial (pre-exertion) level. Grip
      termination time for the affected hand (6.1 seconds) was three times greater than
      that for the unaffected hand (2.1 seconds). Reduction of required activation of
      proximal arm muscles through use of a gravity-compensating arm orthosis decreased
      the grip termination time for the affected hand (p0.05). Conversely, active
      muscle stretch increased grip termination time. Therapies and treatment methods
      which reduce the delay in terminating finger flexor muscle activity may increase
      functional independence for stroke survivors.

PMID- 19163632
TI  - A clinical evaluation on the spatial patterns of non-invasive motor imagery-based
      brain-computer interface in stroke.
AB  - This clinical study investigates whether the spatial patterns of hemiparetic
      stroke patients operating a non-invasive Motor Imagery-based Brain Computer
      Interface (MI-BCI) is comparable to healthy subjects. The spatial patterns for a
      specific frequency range are generated using the common spatial pattern (CSP)
      algorithm, of which is highly successful for discriminating two classes of EEG
      measurements in MI-BCI. The spatial patterns illustrate how the presumed sources
      project on the scalp and are effective in verifying the neurophysiological
      plausibility of the computed solution. The spatial patterns show focused activity
      in ipsilateral as well as contralateral hemisphere with respect to the hand by
      tapping or motor imagery in 2 BCI-artful healthy subjects and 12 BCI-naive
      hemiparetic stroke patients. The results also show that neurophysiologically
      interpretable spatial patterns is more common in performing motor imagery
      compared to finger tapping by hemiparetic stroke patients. Hence, this shows that
      hemiparetic stroke patients are capable of operating MI-BCI.

PMID- 19163633
TI  - A clinical evaluation of non-invasive motor imagery-based brain-computer
      interface in stroke.
AB  - This clinical study investigates whether the performance of hemiparetic stroke
      patients operating a non-invasive Motor Imagery-based Brain-Computer Interface
      (MI-BCI) is comparable to healthy subjects. The study is performed on 8 healthy
      subjects and 35 BCI-naive hemiparetic stroke patients. This study also
      investigates whether the performance of the stroke patients in operating MI-BCI
      correlates with the extent of neurological disability. The performance is
      objectively computed from the 10 x 10-fold cross-validation accuracy of employing
      the Filter Bank Common Spatial Pattern (FBCSP) algorithm on their EEG
      measurements. The neurological disability is subjectively estimated using the
      Fugl-Meyer Assessment (FMA) of the upper extremity. The results show that the
      performance of BCI-naive hemiparetic stroke patients is comparable to healthy
      subjects, and no correlation is found between the accuracy of their performance
      and their motor impairment in terms of FMA.

PMID- 19163634
TI  - Monitoring of global cerebral ischemia using instantaneous phase variation plots.
AB  - In this paper, the derivative of the instantaneous phase of
      electroencephalographic (EEG) signals is used as a basis for monitoring of global
      cerebral ischemia. Visual and quantitative results were obtained from six rodents
      that were subject to 3, 5 and 7 minutes of global ischemic brain injury by
      asphyxic cardiac arrest. Results show that the variations in the instantaneous
      phase are capable of amplifying the variations during the various stages of the
      recovery process and may serve as a novel analytical approach to grade and
      classify brain rhythms during global ischemic brain injury and recovery.

PMID- 19163635
TI  - Multiple vibration intensities and frequencies for bone mineral density
      improvement.
AB  - Devices that deliver controlled quantum vibration intensities at multiple
      frequencies (QVIMF) provide optimal stress to the musculoskeletal system for
      improved bone mineral density and muscle strength. This paper presents
      development of a QVIMF system and pilot study to determine device performance.
      Development is centered on specially-designed actuators that comprise multiple
      nodes of controlled and smooth, but variable rates of contact on a telescoping
      platform through sets of damping subsystems. The combination of specially
      designed actuators and damping subsystems, powered by a DC controlled motor,
      delivers quantum busts of vibration at multiple frequencies resulting in whole
      body vibration. An initial feasibility study involved a 79 year old adult male.
      After IRB approval from both the University of Wisconsin-Milwaukee (UWM) and the
      Zablocki VA Medical Center, Milwaukee, the subject's bone mineral density (BMD)
      was measured by dual x-ray absorptimetry (DXA) at baseline. The subject then
      visited the UWM laboratory for two fifteen-minute vibration sessions per visit,
      three times a week for a total of 60 visits. Post-vibration BMD was again
      measured by DXA. Comparison pre- and post-vibration test results showed increases
      in BMD at the femoral neck, trochanter, total hip, forearm and lower lumbar spine
      (L1-4).

PMID- 19163636
TI  - Modeling and evaluation of human motor skills in a virtual tennis task.
AB  - The present paper develops a virtual tennis system using robotic devices for the
      rehabilitation of upper arm movements, and discusses an evaluation method of
      human motor skills for natural stroke in the dynamic task. In the training, a
      trainee manipulates the handle of an impedance-controlled robot to hit a ball by
      a racket toward the center of a circular target on the wall with considerations
      of motion smoothness and timing. A reference hand motion for the target task is
      clarified through a set of training experiments with 6 health volunteers and
      computationally expressed in the framework of a minimum jerk model. The designed
      index based on the reference model will be effective to quantitatively evaluate
      the recovery of motor skills for natural stroke in the virtual tennis task.

PMID- 19163637
TI  - Development and user evaluation of a virtual rehabilitation system for wobble
      board balance training.
AB  - We have developed a prototype virtual reality-based balance training system using
      a single inertial orientation sensor attached to the upper surface of a wobble
      board. This input device has been interfaced with Neverball, an open source
      computer game to create the balance training platform. Users can exercise with
      the system by standing on the wobble board and tilting it in different directions
      to control an on-screen environment. We have also developed a customized
      instruction manual to use when setting up the system. To evaluate the usability
      our prototype system we undertook a user evaluation study with twelve healthy
      novice participants. Participants were required to assemble the system using an
      instruction manual and then perform balance exercises with the system. Following
      this period of exercise VRUSE, a usability evaluation questionnaire, was
      completed by participants. Results indicated a high level of usability in all
      categories evaluated.

PMID- 19163638
TI  - Wireless control of powered wheelchairs with tongue motion using tongue drive
      assistive technology.
AB  - Tongue Drive system (TDS) is a tongue-operated unobtrusive wireless assistive
      technology, which can potentially provide people with severe disabilities with
      effective computer access and environment control. It translates users'
      intentions into control commands by detecting and classifying their voluntary
      tongue motion utilizing a small permanent magnet, secured on the tongue, and an
      array of magnetic sensors mounted on a headset outside the mouth or an
      orthodontic brace inside. We have developed customized interface circuitry and
      implemented four control strategies to drive a powered wheelchair (PWC) using an
      external TDS prototype. The system has been evaluated by five able-bodied human
      subjects. The results showed that all subjects could easily operate the PWC using
      their tongue movements, and different control strategies worked better depending
      on the users' familiarity with the TDS.

PMID- 19163639
TI  - Predicting end-point locomotion from neuromuscular activities of people with
      spina bifida: a self-organizing and adaptive technique for future implantable and
      non-invasive neural prostheses.
AB  - Neural prosthesis is a promising technique to enable paralyzed patients with
      conditions, such as spinal cord injury or spina bifida (SB), to control their
      limbs independently. However, it remains unknown whether muscle activity detected
      from paralyzed patients can be used to predict and reproduce their altered gait
      patterns that can be employed to provide closed-loop feedback for neural
      prostheses. In this study, we recorded muscle activity of people with SB during
      overground walking and developed a Self-Organizing Adaptive Prediction (SOAP)
      technique for neural prostheses. This technique can provide 80% more accurate
      prediction of end-point impaired locomotion for people with SB compared to
      traditional robust regression. Our results suggest that control of complex neural
      prostheses during locomotion can be achieved by engaging muscle activity as
      intrinsic feedback to generate end-point leg movement.

PMID- 19163640
TI  - Scaling limitations of laser-fabricated nerve electrode arrays.
AB  - A laser technology for manufacturing implantable electrode arrays, using spin-on
      polydimethylsiloxane (PDMS) and platinum foil as materials, was investigated in
      respect to its scaling limitations. The following aspects were analyzed: Minimal
      width and centre-to-centre distance of platinum tracks, the ability of spin-on
      PDMS to flow between platinum tracks with very narrow gaps and the electrical
      insulation properties of thin spin-coated PDMS.

PMID- 19163641
TI  - Multi-finger structure and pulsed-powering operation scheme for CMOS LSI-based
      flexible stimulator for retinal prosthesis.
AB  - Multi-finger structure was proposed to improve flexibility of the CMOS LSI-based
      multi-chip retinal stimulator. A dual-finger retinal stimulator was fabricated
      and its functionality was demonstrated in retinal stimulation experiments on
      rabbit's retina, We also proposed an idea of pulsed-powering operation scheme for
      the multi-chip flexible retinal stimulator. We compared the pulsed-powering
      scheme with conventional one in a simulation, and show that the pulsed-powering
      can be an alternative operation scheme for the neural stimulator that provides an
      improved safety to the biological tissue.

PMID- 19163642
TI  - Application of EEG source localization algorithms to the monitoring of active
      pathways in peripheral nerves.
AB  - Improved techniques for identifying active pathways in peripheral nerves using
      extraneural measurements would have numerous applications in the fields of
      neuroprostheses, neural system engineering, and diagnostics. In this study, we
      propose to approach this issue as an inverse problem of bioelectric source
      localization, using measurements from a multi-contact nerve cuff electrode. This
      problem is a modified version of the electroencephalogram / magneto-encephalogram
      (EEG/MEG) source localization problem. We therefore evaluate the performance of
      two well-known EEG/MEG source localization algorithms, namely sLORETA and
      sFOCUSS, when they are applied to the peripheral nerve problem. sLORETA is found
      to be a potentially viable approach, albeit with limited resolution, while
      sFOCUSS is found to produce too many spurious pathways in the presence of noise.

PMID- 19163643
TI  - A new chronic neural probe with electroplated iridium oxide microelectrodes.
AB  - We have developed a silicon-based neural microelectrode system for long-term
      neural recording and stimulation. Our aim is to design robust silicon-based
      microelectrode arrays that are suitable for implantation into various targets in
      the brain and spinal cord. The microelectrode sites were electroplated with
      iridium oxide, thereby reducing the AC impedance and increasing charge storage
      capacity, compared to gold electrodes. To date, the implanted probe system has
      been able to record resolvable single-unit action potentials for five months in
      the ventral cochlear nucleus of the cats' brainstem.

PMID- 19163644
TI  - A quadratic particle swarm optimization method for magnetic tracking of tongue
      motion in speech disorders.
AB  - We have devised a new magnetic localization technique to accurately track 3-D
      tongue movements during speech and ingestion. A small permanent magnet secured on
      the tongue by tissue adhesives, is utilized as a tracer. The magnetic field
      variations due to tongue motion are detected by three 3-axis magneto-inductive
      sensor modules outside the mouth, and wirelessly transmitted to a computer for
      further processing. The tracer is modeled as a magnetic dipole, which position
      (x, y, z) and orientation (theta, y) are estimated using a quadratic particle
      swarm optimization (PSO) algorithm. This algorithm provides faster and more
      reliable computation compared to the linear PSO. Statistical analysis based on
      hundreds of simulation and experimental results show that using this method,
      calculations are accelerated by a factor of three and the tracer can be localized
      in real-time with approximately 1 mm resolution in position and 2 degrees in
      orientation.

PMID- 19163645
TI  - Modeling transcranial DC stimulation.
AB  - A method to estimate the potential and current density distribution during
      transcranial DC stimulation (tDCS) is introduced. The volume conductor model
      consists of a realistic head model (concerning shape as well as conductivity),
      obtained from TI-, PD- and DT-MR images. The model includes five compartments
      with different conductivities. For the skull and the white matter compartments,
      the conductivities are anisotropic. Using this model, the potentials inside the
      head that are generated by tDCS electrodes positioned on the scalp were computed
      by using the Finite Element Method. The results show that this is a promising
      method for the study of the effects of tDCS.

PMID- 19163646
TI  - Audio aided electro-tactile perception training for finger posture biofeedback.
AB  - Visual information is one of the prerequisites for most biofeedback studies. The
      aim of this study is to explore how the usage of an audio aided training helps in
      the learning process of dynamical electro-tactile perception without any visual
      feedback. In this research, the electrical simulation patterns associated with
      the experimenter's finger postures and motions were presented to the subjects.
      Along with the electrical stimulation patterns 2 different types of information,
      verbal and audio information on finger postures and motions, were presented to
      the verbal training subject group (group 1) and audio training subject group
      (group 2), respectively. The results showed an improvement in the ability to
      distinguish and memorize electrical stimulation patterns correspondent to finger
      postures and motions without visual feedback, and with audio tones aid, the
      learning was faster and the perception became more precise after training. Thus,
      this study clarified that, as a substitution to visual presentation, auditory
      information could help effectively in the formation of electro-tactile
      perception. Further research effort needed to make clear the difference between
      the visual guided and audio aided training in terms of information compilation,
      post-training effect and robustness of the perception.

PMID- 19163647
TI  - Bayesian recursive algorithm for width estimation of freespace for a power
      wheelchair using stereoscopic cameras.
AB  - This paper is concerned with the estimation of freespace based on a Bayesian
      recursive (BR) algorithm for an autonomous wheelchair using stereoscopic cameras
      by severely disabled people. A stereo disparity map processed from both the left
      and right camera images is constructed to generate a 3D point map through a
      geometric projection algorithm. This is then converted to a 2D distance map for
      the purpose of freespace estimation. The width of freespace is estimated using a
      BR algorithm based on uncertainty information and control data. Given the
      probabilities of this width computed, a possible movement decision is then made
      for the mobile wheelchair. Experimental results obtained in an indoor environment
      show the effectiveness of this estimation algorithm.

PMID- 19163648
TI  - Virtual proprioception with real-time step detection and processing.
AB  - Virtual proprioception is a novel device for providing near autonomous
      biofeedback of hemiparetic gait disparity in real time. With virtual
      proprioception a user may modify gait dynamics to develop a more suitable gait in
      tandem with real time feedback. Accelerometers are fundamental to the operation
      of the device, and a thorough consideration of the accelerometry technology space
      for locomotion quantification is included. The role of traumatic brain injury and
      respective decrements to gait quality and proprioceptive feedback are addressed.
      Virtual proprioception conceptual test and evaluation yielded positive results.
      The active 'on' status of the virtual proprioception biofeedback for alternative
      gait strategy was bounded by a 90% confidence level with a 10% margin of error.

PMID- 19163649
TI  - Design and on-line evaluation of type-2 fuzzy logic system-based framework for
      handling uncertainties in BCI classification.
AB  - The practical applicability of brain-computer interface (BCI) technology is
      limited due to its insufficient reliability and robustness. One of the major
      problems in this regard is the extensive variability and inconsistency of brain
      signal patterns, observed especially in electroencephalogram (EEG). This paper
      presents a fuzzy logic (FL) approach to the problem of handling of the resultant
      uncertainty effects. In particular, it outlines the design of a novel type-2 FL
      system (T2FLS) classifier within the framework of an EEG-based BCI, and examines
      its on-line applicability in the presence of shortand long-term nonstationarities
      of spectral EEG correlates of motor imagery (imagination of left vs. right hand
      movement). The developed system is shown to effectively cope with real-time
      constraints. In addition, a comparative post hoc analysis has revealed that the
      proposed T2FLS classifier outperforms conventional BCI methods, like LDA and SVM,
      in terms of the maximum classification accuracy (CA) rates by a relatively small,
      yet statistically significant, margin.

PMID- 19163650
TI  - Ultrasound induced increase in excitability of single neurons.
AB  - The aim of this study was to carefully assess the level of modulation in
      electrical excitability of single neurons with the application of high frequency
      ultrasound. High frequency tone bursts of ultrasound have been shown to
      dramatically increase the spike frequency of primary hippocampal neurons in
      culture. In addition, these ultrasonic bursts also induce silent or still
      developing neurons to fire. Results indicate that the increase in excitability is
      largely mediated by mechanical effects and not thermal effects of ultrasound.
      Future studies on culture models exposed to varying ultrasound protocols may
      provide insight into the feasibility of using ultrasound as a means for
      neurostimulation studies conducted on brain slice and in vivo models.

PMID- 19163651
TI  - Powered AFO for Achilles tendon rupture.
AB  - This paper proposes a powered ankle foot orthosis (AFO) for the treatment of a
      ruptured Achilles tendon. Usually, conservative orthosis treatment requires about
      two months, and a motionless ankle degrades activities of daily living (ADL). It
      is difficult to go to school or work on foot, and a pair of crutches is needed to
      go up and down stairs. In order to improve the ADL, an electric powered AFO has
      been designed to improve the ability to walk with a fixed ankle joint. The sole
      of the proposed AFO is equipped with an electric actuator. The prototype actuator
      consists of Nd magnets and electromagnets and is lightweight and battery driven.
      The actuator can switch the upright posture and the stepped forward posture of
      the patient. In an experiment, the use of this electric AFO made it possible to
      walk and to ascend and descend stairs with a fixed ankle joint.

PMID- 19163652
TI  - Shared control strategies for obstacle avoidance tasks in an intelligent
      wheelchair.
AB  - In this paper we present a method of shared control strategy for an intelligent
      wheelchair to assist a disable user in performing obstacle avoidance tasks. The
      system detects obstacles in front of the wheelchair using a laser range finder
      sensor. As the wheelchair moves the information from the laser range finder is
      combined with data from the encoders mounted in its driving wheels to build a 360
      degrees real-time map. The accuracy of the map is improved by eliminating the
      systematic error that would result from both the uncertainty of effective
      wheelbase and unequal driving wheel diameters. The usable wheelchair accessible
      space is determined by including the actual wheelchair dimensions in producing
      the real-time map. In making a decision the shared control method considers the
      user's intentions via the head-movement interface, accessible space of the
      environment and user safety. The experiments show promising results in the
      intelligent wheelchair system.

PMID- 19163653
TI  - Supervisory controller design for a robot-assisted reach-to-grasp rehabilitation
      task.
AB  - The goal of this project is to develop a high-level controller to provide
      reference trajectories automatically to the low-level controller of a
      rehabilitation robotic device in reach-to-grasp task. The high-level controller,
      which is the supervisory controller, is an event driven, asynchronous discrete
      event system (DES), described by a finite automaton. Extensive simulations are
      performed using the supervisory controller for a reach-to-grasp rehabilitation
      task. The results demonstrate the feasibility and convenience of the proposed
      supervisory controller.

PMID- 19163654
TI  - Measurement of reaching movement with 6-DOF upper rehabilitation system
      'Robotherapist'.
AB  - In recent years, the needs for rehabilitation support systems are increasing,
      which use robot technology and virtual reality technology. Applying these
      technologies make efficient rehabilitation possible. We have developed 6-degrees
      of-freedom (DOF) upper rehabilitation support system to evaluate synergy pattern
      of stroke survivors and to train stroke survivors, named 'Robotherapist'. When
      stroke survivors who can move plural joints only along a certain constant pattern
      called synergy pattern do reaching movement, some of them cannot keep their
      posture of the arm normal, but can move their hand along the aim orbit. In this
      study, we experiment on a measurement of reaching movement with our system and
      make a model of movement peculiar to stroke survivors and a model of movement of
      healthy people. Additionally, we propose application software for reaching
      training with this model. In this paper, we report measurement of reaching
      movement and propose application software for reaching training with our system.

PMID- 19163655
TI  - A system design of gait training device for monoplegia patients.
AB  - In this paper, we present a system design about a gait training device for
      monoplegia patients and aged people. In a conventional gait training program, the
      monoplegia patient takes a step leaning on the parallel guide bar or helped by a
      therapist's arm support. But this method often does not give satisfactory result
      since the method fails to correct the irregular posture of the patient. The new
      training device has been in need for gait disorder patients, monoplegia patients
      and aged people. The gait training device for the patients is divided into four
      main units, gait phase detecting unit, lower panel controlling unit, lower limb
      pulling and releasing unit and additional supplementary unit for safety of the
      patients. The training device to be presented exhibits stableness in its
      operation and it may improve the effect of gait rehabilitation training compared
      to the conventional gait training method.

PMID- 19163656
TI  - Effect of the different winding methods of coil on electromagnetic field during
      transcranial magnetic stimulation.
AB  - Transcranial magnetic stimulation (TMS) is a powerful, non-invasive tool for
      investigating functions in the brain. The target inside the head is stimulated
      with eddy currents induced in the tissues by the time-varying magnetic field. TMS
      has been used in several applications in medical and clinical research which
      include brain mapping, treatment of mood disorder and schizophrenia, treatment of
      epilepsy, treatment of chronic pain and so on. The stimulation effect can be
      affected by the stimulation intensity. For coils with the same shape, different
      winding methods make the coil have different stimulation intensity. In this
      paper, three different methods for winding circular coils are discussed. The
      electromagnetic fields induced by the three different circular coils were
      analyzed. The results show that the circular coil with the pancake coil winding
      has the strongest stimulation intensity.

PMID- 19163657
TI  - Design optimization of an above-knee prosthesis based on the kinematics of gait.
AB  - A dynamic model of an above-knee prosthesis during the complete gait cycle was
      developed. The model was based on a two-dimensional multi-body mechanical system
      and included a hydraulic and an elastic controller for the knee and a kinematical
      driver controller for the prosthetic ankle. The equations of motion were driven
      using Lagrange method. Simulation of the foot contact was conducted using a two
      point penetration contact model. The knee elastic and hydraulic controller units,
      the knee extension stop, and the kinematical driver controller of the ankle were
      represented by a spring and a dashpot, a nonlinear spring, and a torsional spring
      damper within a standard prosthetic configuration. The hip trajectory and net
      joint moment were considered as the initial conditions of the coupled
      differential equations. Design optimization of the prosthesis, to achieve the
      closest knee flexion pattern to that of the normal gait, resulted in a good
      correlation; the average differences with normal data were 3.3 and 3.4 deg for
      prosthetic knee and ankle joints, respectively. A parametric study showed that
      both increase and decrease of the stiffness by 50% caused an earlier knee flexion
      in stance phase and a lower knee flexion in swing phase. The effect of hydraulic
      controller damping coefficient on the flexion pattern of the prosthetic knee and
      ankle was only significant in the swing phase of the gait cycle.

PMID- 19163658
TI  - Task oriented joint moment generation in virtual reality environment using a
      goniogram controlled dynamometer.
AB  - In the paper the knee joint goniogram based dynamometer control applying virtual
      reality environment task is presented. The virtual reality task was controlled by
      assessed voluntarily generated joint moment and the movement of the dynamometer
      was synchronized with the knee goniogram assessed during computer gait analysis.
      The subject was requested to follow the task requiring a voluntary generation of
      joint moment adequate to the one assessed in gait analysis. In preliminary study
      10 neurologically intact volunteers participated to test the application in
      various conditions (increasing speed and difficulty level) in order find the
      feasible protocol for motor control learning in people with motor control
      impairment.

PMID- 19163659
TI  - Development of virtual reality exercise of hand motion assist robot for
      rehabilitation therapy by patient self-motion control.
AB  - This paper presents a virtual reality-enhanced hand rehabilitation support system
      with a symmetric master-slave motion assistant for independent rehabilitation
      therapies. Our aim is to provide fine motion exercise for a hand and fingers,
      which allows the impaired hand of a patient to be driven by his or her healthy
      hand on the opposite side. Since most disabilities caused by cerebral vascular
      accidents or bone fractures are hemiplegic, we adopted a symmetric master-slave
      motion assistant system in which the impaired hand is driven by the healthy hand
      on the opposite side. A VR environment displaying an effective exercise was
      created in consideration of system's characteristic. To verify the effectiveness
      of this system, a clinical test was executed by applying to six patients.

PMID- 19163660
TI  - The numeric calculation of eddy current distributions in transcranial magnetic
      stimulation.
AB  - Transcranial magnetic stimulation (TMS) is a method to stimulate neurons in the
      brain. It is necessary to obtain eddy current distributions and determine
      parameters such as position, radius and bend-angle of the coil to stimulate
      target area exactly. In this study, we performed FEM-based numerical simulations
      of eddy current induced by TMS using three-dimentional human head model with
      inhomogeneous conductivity. We used double-cone coil and changed the coil radius
      and bend-angle of coil. The result of computer simulation showed that as coil
      radius increases, the eddy current became stronger everywhere. And coil with bend
      angle of 22.5 degrees induced stronger eddy current than the coil with bendangle
      of 0 degrees. Meanwhile, when the bend-angle was 45 degrees, eddy current became
      weaker than these two cases. This simulation allowed us to determine appropriate
      parameter easier.

PMID- 19163661
TI  - Design and implementation of visual-haptic assistive control system for virtual
      rehabilitation exercise and teleoperation manipulation.
AB  - This paper describes the design and implementation of a control system that
      integrates visual and haptic information to give assistive force feedback through
      a haptic controller (Omni Phantom) to the user. A sensor-based assistive function
      and velocity scaling program provides force feedback that helps the user complete
      trajectory following exercises for rehabilitation purposes. This system also
      incorporates a PUMA robot for teleoperation, which implements a camera and a
      laser range finder, controlled in real time by a PC, were implemented into the
      system to help the user to define the intended path to the selected target. The
      real-time force feedback from the remote robot to the haptic controller is made
      possible by using effective multithreading programming strategies in the control
      system design and by novel sensor integration. The sensor-based assistant
      function concept applied to teleoperation as well as shared control enhances the
      motion range and manipulation capabilities of the users executing rehabilitation
      exercises such as trajectory following along a sensor-based defined path. The
      system is modularly designed to allow for integration of different master devices
      and sensors. Furthermore, because this real-time system is versatile the haptic
      component can be used separately from the telerobotic component; in other words,
      one can use the haptic device for rehabilitation purposes for cases in which
      assistance is needed to perform tasks (e.g., stroke rehab) and also for
      teleoperation with force feedback and sensor assistance in either supervisory or
      automatic modes.

PMID- 19163662
TI  - Rehabilitation instrument for prevent contracture of ankle using the pneumatic
      balloon actuator.
AB  - A rehabilitation instrument for ankle contracture prevention is proposed. Its
      uses a tendon drive system using a pneumatic balloon. This instrument is intended
      to be carried and installed easily at the time of use in a place like a medical
      institution. This instrument is for use by people such as those with flaccid
      hemiplegia. The ankle is moved when it is worn; ankle contracture can be
      prevented. The device comprises an actuator, a power transfer mechanism, and
      ankle foot orthosis. A tendon drive system using a pneumatic balloon was adopted
      as the actuator of this instrument. It consists of a tendon and a silicone tube.
      Both ends of the silicone tube are closed and the tube expands like a balloon
      with the supply of air, which distends the silicone tube and pulls the tendon.
      The system is compact and has high power. Furthermore, it is very lightweight
      because of its composition material and structure. This paper describes a study
      of characteristics of the tendon drive system using a pneumatic balloon, along
      with the composition and operation of a rehabilitation instrument for prevention
      of ankle contracture. Results of operation tests on the instrument are also
      presented.

PMID- 19163663
TI  - A light sterilizable pipette device for the in vivo estimation of human soft
      tissues constitutive laws.
AB  - This paper introduces a new light device for the in vivo estimation of human soft
      tissues constitutive laws. It consists of an aspiration pipette able to meet the
      very severe sterilization and handling issues imposed during surgery. The
      simplicity of the device, free of any electronic circuitry, allows using it as an
      ancillary instrument. The deformation of the aspired tissue is imaged via a
      mirror using an external camera. The paper describes the experimental setup as
      well as the protocol that should be used during surgery. First feasibility
      measurements are shown for human tongue and forearm skin.

PMID- 19163664
TI  - Resolving subjects and measuring observer/subject distances with a thermal
      tactile imager.
AB  - Visually-impaired people have difficulty detecting objects beyond the reach of a
      cane. We functionally coupled a far-infrared camera to a linear array of tactile
      elements to create a thermal tactile viewer that enhances environmental
      awareness. Users may scan such a device across a scene to spatially locate
      people. We observed in a series of acuity-measuring tasks, at twenty feet of
      observer/subject separation, observers could resolve two people standing four
      inches apart (a separation angle of 1 degrees ) and locate the angular position
      of people within a room with 78% accuracy. Additionally, when employing a
      technique involving two sweeps from two observation points separated by
      approximately an arm span, subjects correctly reported observer/subject
      separation distance with 60% accuracy. These observations suggest the technique
      of information transfer provided by a thermal tactile viewing device provides the
      fundamental acuity required for an assistive locating device.

PMID- 19163665
TI  - Design of a continuous passive and active motion device for hand rehabilitation.
AB  - This paper presents the design of a novel, portable device for hand
      rehabilitation. The device provides for CPM (continuous passive motion) and CAM
      (continuous active motion) hand rehabilitation for patients recovering from
      damage such as flexor tendon repair and strokes. The device is capable of
      flexing/extending the MCP (metacarpophalangeal) and PIP (proximal
      interphalangeal) joints through a range of motion of 0 degrees to 90 degrees for
      both the joints independently. In this way, typical hand rehabilitation motions
      such as intrinsic plus, intrinsic minus, and a fist can be achieved without the
      need of any splints or attachments. The CPM mode is broken into two subgroups.
      The first mode is the use of preset waypoints for the device to cycle through.
      The second mode involves motion from a starting position to a final position, but
      senses the torque from the user during the cycle. Therefore the user can control
      the ROM by resisting when they are at the end of the desired motion. During the
      CPM modes the device utilizes a minimum jerk trajectory model under PD control,
      moving smoothly and accurately between preselected positions. CAM is the final
      mode where the device will actively resist the movement of the user. The user
      moves from a start to end position while the device produces a torque to resist
      the motion. This active resistance motion is a unique ability designed to mimic
      the benefits of a human therapist. Another unique feature of the device is its
      ability to independently act on both the MCP and PIP joints. The feedback sensing
      built into the device makes it capable of offering a wide and flexible range of
      rehabilitation programs for the hand.

PMID- 19163666
TI  - Design framework for a simple robotic ankle evaluation and rehabilitation device.
AB  - This paper juxtaposes simple yet sufficiently general robotic mechanisms for
      ankle function evaluation, measurement and physiotherapy. For the choice, design
      and operation of the mechanism, a kinematics model of foot is adopted from
      biomechanics, based on the hypothesis that foot kinematics are similar to a 2R
      serial robot. We undertake experiments, using a 3D scanner and an inertial sensor
      in order to fully specify the design framework by studying a larger sample of
      healthy subjects. Our experimental analysis confirms and enhances the 2R foot
      model, and leads us to the choice of the specific mechanism. We compute the
      required workspace and thus address the issues required for a complete and
      efficient design. The robot must be capable to perform several multi-axis motions
      and sustain a significant range of forces and torques. We compare mechanisms
      based on serial and parallel robots, and choose a parallel tripod with an extra
      rotation axis for its simplicity, accuracy and generality.

PMID- 19163667
TI  - Control strategies for smart prosthetic hand technology: an overview.
AB  - A chronological overview of the applications of control theory to prosthetic hand
      is presented. The overview focuses on hard computing or control techniques such
      as multivariable feedback, optimal, nonlinear, adaptive and robust and soft
      computing or control techniques such as artificial intelligence, neural networks,
      fuzzy logic, genetic algorithms and on the fusion of hard and soft control
      techniques. This overview is not intended to be an exhaustive survey on this
      topic and any omissions of other works is purely unintentional.

PMID- 19163668
TI  - Bayesian-based diagnostic decision-support for pediatrics.
AB  - The goal of this project was to develop a Pediatric Decision Support system (PDS)
      that allows a resident physician to define a patient case based on symptoms
      (diagnostic signs and test results) and generates a list of possible diagnoses
      based on the World Health Organization's International Classification of Diseases
      (ICD10). The intent is to improve the diagnostic approach taken by resident
      physicians and eventually become a training tool in medical education programs.

PMID- 19163669
TI  - Multi-dimensional temporal abstraction and data mining of medical time series
      data: trends and challenges.
AB  - This paper presents emerging trends in the area of temporal abstraction and data
      mining, as applied to multi-dimensional data. The clinical context is that of
      Neonatal Intensive Care, an acute care environment distinguished by multi
      dimensional and high-frequency data. Six key trends are identified and classified
      into the following categories: (1) data; (2) results; (3) integration; and (4)
      knowledge base. These trends form the basis of next-generation knowledge
      discovery in data systems, which must address challenges associated with
      supporting multi-dimensional and real-world clinical data, as well as null
      hypothesis testing. Architectural drivers for frameworks that support data mining
      and temporal abstraction include: process-level integration (i.e. workflow
      order); synthesized knowledge bases for temporal abstraction which combine
      knowledge derived from both data mining and domain experts; and system-level
      integration.

PMID- 19163670
TI  - Integration of new technology in a legacy system for collecting medical data -
      challenges and lessons learned.
AB  - Integrating new technology into a legacy medical system can be very challenging.
      Completely new systems cannot always be built due to the high cost of medical
      equipment, thus integrating some new technology into an existing system may be
      required. This paper looks at the issues and challenges surrounding the
      integration of new components into a legacy system for collecting medical data.
      We discuss how the issues were solved, the lessons learned, and how future
      upgrades can be made more easily.

PMID- 19163671
TI  - Analysis of computer-supported oral anticoagulant treatment follow-up workflow.
AB  - The objective is to explore the impact of computer-supported reorganization of
      oral anticoagulation treatment follow-up in a multi-year, multi-clinic pilot
      study. The focus is on how changes in workflow, namely in anticoagulation
      workload distribution between nurses and physicians, interact with the quality of
      care immediately after initial deployment and then later on during the pilot
      study. The results show that decreases in the physician's time allocation did not
      result in a lessened quality of care during periods after reorganization.

PMID- 19163672
TI  - Pursuit for the knowledge of a cardiology expert - a hidden poll methodology.
AB  - The human-computer interaction became a routine and intuitive task of a
      cardiologist. The ECG interpretation software may be modified to trace the
      interaction history and to provide the information useful for the investigation
      of the expert preferences. Because the consciousness of the investigated expert
      is not engaged as much as in the disclosed questionnaire, the response is not
      biased making the measurement more objective. The paper demonstrates metrological
      backgrounds and the use of a hidden poll in the investigation of the priority of
      ECG diagnostic parameters in context of various cardiac diseases. This knowledge,
      difficult to be derived otherwise, is applied in the disease-oriented assessment
      of the diagnostic quality.

PMID- 19163673
TI  - Imputation of missing values by integrating neural networks and case-based
      reasoning.
AB  - Missing values in a medical database present a problem when trying to develop a
      prediction model for a broad range of patients, if the data are not missing at
      random. We present a data imputation approach for physiologic parameters that
      incorporates individualized case information into the imputed values. We replaced
      missing values in a neonatal intensive care unit (NICU) database with relevant
      data by integrating aspects of artificial neural networks (ANNs) and case-based
      reasoning (CBR).

PMID- 19163674
TI  - Emergency recognition system based on multimodal information.
AB  - This paper aims to propose an emergency recognition system using multimodal
      information extracted by an image processing module, a voice processing module,
      and a gravity sensor processing module. Each processing module detects predefined
      events such as moving, stopping, fainting, and transfer them to the multimodal
      integration module. Multimodal integration module recognizes emergency situation
      by using the transferred events and rechecks it by asking the user some question
      and recognizing the answer. The experiment was conducted for a faint motion in
      the living room and bathroom. The results of the experiment show that the
      proposed system is robust than previous methods and effectively recognizes
      emergency situations at various situations.

PMID- 19163675
TI  - OLDES: new solution for long-term diabetes compensation management.
AB  - EU project OLDES (Older People's e-services at home) aims at developing a very
      low cost and easy to use entertainment and health care platform designed to ease
      the life of older people in their homes. The platform is based on a PC
      corresponding to Negroponte's paradigm of a 100 $ device. OLDES combines user
      entertainment services (through easy-to-access thematic interactive channels and
      special interest forums supported by animators) and health care facilities. The
      pilot case study of diabetes type II compensation under the OLDES framework is
      presented. Apart from measurement of continuous glucose, blood pressure and
      weight, the user feeds into OLDES system food daily consumption using interactive
      food scales via user friendly software interface designed by user-centered design
      paradigm and obtains advice if necessary.

PMID- 19163676
TI  - Two intelligent order viewers for chronic condition patients on clinical
      information system.
AB  - The computerization of patient data is proceeding and the amount of patient
      records has greatly increased. However, physicians have limited time to review
      and process patient records. In order to use these records effectively, medical
      institutions need to access the information in a variety of forms. This paper
      comparatively describes two intelligent viewers that are SAKURA-Viewer and FUJI
      Viewer. These viewers reorganize order-related data. SAKURA-Viewer is based on a
      concept hierarchy method and focuses the view of consolidated information. This
      viewer represents order history from two viewpoints simultaneously to eliminate
      semantic redundancies. FUJI-Viewer is based on two-dimensional mapping method and
      focuses the flow of periodic information. This viewer represents differences
      between the plan history and the order history to manage a long-term test order
      history and test plan history concurrently. These viewers also support data entry
      methods that input order-related data efficiently and accurately. This interface
      reduces the workload of the medical stuff. These intelligent viewers are
      incorporated into a clinical information system.

PMID- 19163677
TI  - A low cost light diffuser made of metal coil.
AB  - We proposed a low cost flexible light diffuser made of metal coil to obtain an
      appropriate light dose against certain laser therapies in narrow bending organs.
      We investigated experimentally the diffusion light dose of prototype coils made
      of stainless steel (sus304). We measured the diffusion light intensity of the
      prototype coils along the irradiation direction and the circumferential direction
      with the various pitch distances of the prototype coils and numerical aperture
      (NA) of laser light beam as the characteristic parameters of the light diffusion.
      We measured the temperature elevation of the prototype coils to study the waste
      energy of these prototype coils. The FWHM on the light intensity along the
      prototype coils marked up to 12.8mm with the constant pitch distance of 0.09 mm
      and the fiber output light NA of 0.038. The FWHM on the light intensity was
      improved to 13.7 mm with the composite pitch distance coils of which the pitch
      distances were 0.09 mm in the proximate and 0.18 mm in the distal. Since the
      efficiency of the diffusion irradiation against the fiber output was typically
      7.7% in the prototype coils of which the surface reflectance was 50%,
      approximately 90% of the laser light energy was transferred to the temperature
      elevation. We estimated the practical diffusion efficiency around 75% using the
      high reflection of the prototype coils surface up to 90%.

PMID- 19163678
TI  - Selective laser suture lysis with a compact, low-cost, red diode laser.
AB  - The argon (blue-green) laser is currently used for vaporization of sutures during
      ophthalmic surgery. However, previous studies have reported more effective laser
      suture lysis and a lower rate of complications using the krypton (red) laser. Red
      wavelengths are selectively absorbed by the nylon sutures, but are minimally
      absorbed by adjacent tissue, and not absorbed by hemoglobin, unlike the argon
      laser wavelengths. More compact and less expensive red diode lasers have recently
      become commercially available for surgical applications. This study explores the
      use of a compact, lowpower, red diode laser for selective laser suture lysis. A
      225 mW, 660-nm diode laser was used to vaporize 10-0 nylon sutures in human
      cornea samples with a single laser pulse, pulse energy of 150 mJ, pulse duration
      of 100 ms, and spot diameter of 55 mum. The red diode laser may represent an
      inexpensive, compact, and safer alternative laser for use in laser suture lysis
      during ophthalmic surgery.

PMID- 19163679
TI  - Photosensitization reaction-induced electrical blockade in myocardial tissue.
AB  - We proposed the application of photodynamic therapy (PDT) as a new type of atrial
      fibrillation treatment. PDT is well known as a practical cancer treatment using
      cytotoxicity of reactive oxygen species generated by the photochemical
      interaction. We predicted that the photocytotoxic effect induced by PDT might
      cause electrical blockade in myocardial tissue. We studied the electrical
      blockade induced by the PDT with talaporfin sodium in vitro, ex vivo, and in
      vivo. The cell lethality measurement using rat cardiac myocytes confirmed the PDT
      induced photocytotoxic effect and its dependence on the loading time of the
      photosensitizer. In ex vivo experiment using rat right ventricle, the PDT caused
      a shutdown of the stimulated electrical signal propagation. The long-lasting
      atrioventricular block induced by the PDT was obtained in vivo experiment with
      rat heart. These results revealed the possibility of atrial fibrillation
      treatment with the PDT.

PMID- 19163680
TI  - Finite element analysis of the needle type applicator made of shape memory alloy.
AB  - In this paper, we propose a new heating method in which we use shape memory alloy
      (SMA) in a needle type applicator for brain tumor hyperthermia. In order to
      expand the heating area of a needle type applicator and to control the heating
      pattern for various sizes of tumors, some kinds of SMA needle type applicators
      were developed. To apply the proposed heating method safely to clinical
      hyperthermia, it is necessary to make appropriate thermal distribution to the
      region of the brain tumor. However, it is not easy to predict the three
      dimensional temperature distribution during the human brain tumor hyperthermia.
      Therefore, we estimated the temperature distribution inside the agar phantom by
      the finite element method (FEM). Here, first, the computer simulation results of
      temperature distributions under the different heating times are discussed.
      Second, a comparison of the heating properties obtained by using the needle type
      electrodes made of different shaped SMA is discussed. From these results, it is
      confirmed that the proposed heating method can expand the heating area and
      control the heating pattern for the various sizes of brain tumors.

PMID- 19163681
TI  - Electromagnetic-thermal analysis of an RF rectangular resonant cavity applicator
      for hyperthermia targeting deep-seated tumors using a human model with blood flow
      and fat layer.
AB  - Maxwell's and heat transfer equations were coupled and solved to determine the
      heating characteristics of an RF rectangular resonant cavity applicator for
      hyperthermia before the clinical stage. A simple human model with blood flow and
      a fat layer was constructed. The region unaffected by tumor was shielded from
      electromagnetic fields by using conductive caps. The surface of the human model
      that was exposed to the electromagnetic fields was cooled with pure water bolus.
      Calculated results show that this applicator can heat a deep-seated tumor.

PMID- 19163682
TI  - Improvement of needle type applicator made of shape memory alloy.
AB  - This paper discusses radio frequency (RF) interstitial hyperthermia for brain
      tumors with a developed needle type applicator made of a shape memory alloy
      (SMA). The problem with the heating method of interstitial hyperthermia is the
      small heating area. So, we proposed a new heating method using a needle type
      electrode made of SMA which consists of nickel (Ni), copper (Cu) and titanium
      (Ti) for expanding the heating area. Here, we proposed the heating method that
      the leading end of needle type electrode was divided into four parts and the
      leading end spreads in four directions with a temperature rise. First, the
      proposed RF interstitial hyperthermia system with the SMA needle was presented.
      Second, the results obtained by the experimental heating of the agar phantom by
      using the developed SMA needle type applicator were presented. Third, comparing
      experimental results, we discussed the heating properties of the developed
      system. Finally, from these results, it is confirmed that the developed needle
      type applicator made of SMA is useful for wide heating by invasive hyperthermia.

PMID- 19163683
TI  - Development of automatic impedance matching system for hyperthermia treatment
      using resonant cavity applicator.
AB  - In this paper, we discuss a new system to make impedance matching automatically
      for a re-entrant resonant cavity applicator for brain tumor hyperthermia
      treatment non-invasively. We have already discussed about the effectiveness of
      the heating method using manual type impedance matching controller, with
      experiments of heating an agar phantom and computer simulations. However, it
      becomes difficult to perform an accurate impedance matching as resonant frequency
      becomes high. Here, in order to make a more accurate impedance matching, we
      developed the automatic impedance matching system (AIMS). We noticed that the
      reflected power was generated when the impedance matching was not complete. In
      this system, therefore, to reduce the reflected power fed back, the stepping
      motor to turn the dial of variable capacitors is controlled by developed
      software. To evaluate the developed AIMS, the experiments of heating the agar
      phantom were performed. From these results, we found that the temperature rise of
      the agar phantom by using AIMS was about 180% of using manual type controller
      under the same heating condition. It was found that the proposed system was very
      effective for hyperthermia treatment using resonant cavity applicator even when
      the resonant frequency was high.

PMID- 19163684
TI  - Regional heating by insertion of dielectrics and rotation of the focused electric
      field in the hyperthermia.
AB  - We have developed a cancer treatment system that utilizes a reentrant resonant
      cavity to heat the localized deep lesion inside the living body non-invasively.
      In this study we focused the electric field distribution by loading a dielectric
      between the reentrant electrodes and an object, and attempted to optimize the
      shape and the size of the loaded dielectric. The basic experiment using prototype
      equipment and numerical analysis using the three-dimensional finite element
      method indicated that we can improve the focusing effect of 10-20 % compared with
      our previous heating system by the loaded dielectric. In addition, we confirmed
      that the focusing effect of the electric field distribution can be achieved by
      rotating the applicator in order to accurately heat a small localized region of
      30-50 mm in diameter.

PMID- 19163685
TI  - Noninvasive temperature measurement method for hyperthermia treatment using
      ferromagnetic implant with low curie temperature.
AB  - Induction heating using 'ferromagnetic implant with low Curie temperature
      (FILCT)' is one of the heating methods for hyperthermia. However, a lot of energy
      is needed to heat malignant tumors; the heating efficiency has to be improved. In
      order to address this problem, we propose using FILCT as a probe for temperature.
      A non-invasive temperature measurement system was developed based on this
      approach. A key advantage of this system is that it can noninvasively distinguish
      whether the temperature of FILCT has reached the Curie temperature or not. As a
      result, materials with high heating efficiency may be used.

PMID- 19163686
TI  - Radiofrequency dosimetry in subjects implanted with metallic straight wires: a
      numerical study.
AB  - A numerical study to investigate the effects of the exposure to electromagnetic
      fields (EMF) at 900 and 1800 MHz on biological tissues implanted with thin
      metallic structures has been carried out, using the finite difference time domain
      (FDTD) solution technique. The results of the model show that the presence of a
      metallic wire yields to a significant increase in the local specific energy
      absorption rate (SAR). The present standards and/or guidelines on safe exposures
      of humans to EMF does not cover persons with implanted devices and thus the
      threshold levels to define safe exposure conditions might not apply in presence
      of high SAR gradients, such as the ones generated by thin metallic implanted
      objects. However, exposure to EMF fields below the actual safe levels even in
      presence of thin conductive structures cause rather low temperature rises (1
      degrees C).

PMID- 19163687
TI  - Allocation of processing resources between right and left spatial attention.
AB  - Researches in Visual Evoked Potentials (VEPs) showed that spatial attention
      exerted an amplitude modulation of the attended inputs in primary visual cortex
      during the interval 80-200 ms following stimulus onset. VEPs data of a classical
      left or right visual field selective attention experiment were analyzed by the
      method of spatial principal component analysis (PCA) and statistical analysis.
      The results indicated that allocation of processing resources in humans had
      differences between right and left spatial attention when stimuli appeared in
      unattended position. Transferring attention from right to left demanded more
      energy than shifting attention from left to right. It implied that right-handed
      subjects might have an advantage in right spatial attention.

PMID- 19163688
TI  - Subspace techniques to remove artifacts from EEG: a quantitative analysis.
AB  - In this work we discuss and apply projective subspace techniques to both
      multichannel as well as single channel recordings. The single-channel approach is
      based on singular spectrum analysis(SSA) and the multichannel approach uses the
      extended infomax algorithm which is implemented in the opensource toolbox EEGLAB.
      Both approaches will be evaluated using artificial mixtures of a set of selected
      EEG signals. The latter were selected visually to contain as the dominant
      activity one of the characteristic bands of an electroencephalogram (EEG). The
      evaluation is performed both in the time and frequency domain by using
      correlation coefficients and coherence function, respectively.

PMID- 19163689
TI  - A least square DFT method for sub-sample fetal heart rate estimation under noisy
      conditions.
AB  - In this paper, we consider fundamental period estimation problem for fetal ECG
      waveforms. By means of a signal separation algorithm, a fetal ECG waveform can be
      obtained from abdominal ECG of a pregnant woman which contains both maternal and
      fetal ECG waveforms. We develop a new fundamental period estimator based on
      minimization of a cost function which measures the least square differences
      between the discrete Fourier transform (DFT) of the original fetal ECG waveform
      and the DFT of its circularly shifted form. This cost function attains to its
      minimum when the circular shift corresponds to integer multiples of the
      fundamental period. We minimize this cost function to obtain an integer
      fundamental period estimate. We also minimize this cost function with a gradient
      descent method to achieve sub-sample precision in fundamental period estimation.
      With two examples, we demonstrate applications of this method to fetal ECG
      waveforms and compare its performance to the well-known generalized correlation
      method.

PMID- 19163690
TI  - Application of multiple correspondence analysis to asses the relation between
      time after transplantation and sympathetic activity in cardiac transplant
      recipient.
AB  - The aim of the present study was to evidence that the heart reinnervation can
      occur and it is related with the time after transplantation (evolution with
      time). Data were evaluated using Multiple Correspondence Analyses (MCA), which is
      the ideal method to study the relation, probably nonlinear, between the Time
      After Transplantation (TAT) and the probable restoration of normal heart rate
      responses of sinus node regulated by the autonomic nervous system. Twenty four
      nonrejecting transplant recipients (60 +/- 48 months after transplantation) and
      nine healthy subjects were studied by heart rate variability parameters. Results
      showed that sympathetic activity is restored some time after transplantation.
      Until 48 months, the recent HTR are in direct correlation to low values SD and LF
      and for the oldest transplant recipient, these parameters are similar to that
      observed in normal subjects.

PMID- 19163691
TI  - Evaluation of a Neyman-Pearson heart-rate turbulence detector.
AB  - In this paper we propose and evaluate a Neyman-Pearson approach to detect and
      characterize heart-rate turbulence after ventricular premature beats (VPB). For
      quantification of the detection performance an evaluation dataset was built based
      on real RR interval series. The ROC curves obtained from the test set show the
      proposed method to outperform the detection capability of the two parameters
      currently used to quantify turbulence: turbulence onset and turbulence slope.

PMID- 19163692
TI  - fMRI binary detection of brain activated regions with graph-cuts.
AB  - The functional Magnetic Resonance Imaging (fMRI) is a technique with increasing
      applications in studying the brain function. The blood-oxygenation-level
      dependent (BOLD) is a fMRI method that allows the detection of brain activated
      regions after the application of an external stimulus, e.g., visual or auditive.
      This technique is based on the assumption that the metabolism increases in
      activated areas as well as the oxygen uptake. Analising this information is a
      challenging problem because the BOLD signal is very noisy and its changes due to
      the application of a stimulus are very weak. Therefore, the detection of temporal
      correlations with the applied stimulus requires sophisticated statistical
      algorithms to understand if the changes on the BOLD signal are pure noise or are
      related with the applied stimulus, called paradigm in the fMRI scope.

PMID- 19163693
TI  - Quantitatively Interpreting fMRI signal.
AB  - Quantitative relationships among the neurophysiologic processes that link
      neuronal activity to hemodynamic change is extremely important to interpret the
      functional magnetic resonance imaging (fMRI) signals. In this article the
      neurovascular coupling relationship was noninvasively studied in the human visual
      cortex. Graded neuronal/hemodynamic suppression conditions were generated using a
      paired-stimulus paradigm. Visual evoked potential (VEP) was measured to quantify
      neuronal activity. Hemodynamic activities were measured and quantified by
      perfusion changes. All quantification was normalized to the same activation
      condition using a single-stimulus paradigm within each experimental session. The
      results reveal: (i) there is a tight neurovascular coupling at graded neuronal
      suppression conditions; (ii) the neurovascular coupling relationship contains a
      subtle, but significant, nonlinear component; (iii) the linear model,
      nevertheless, is still a good approximation reflecting the neurovascular coupling
      relationship.

PMID- 19163694
TI  - A supervised method to assist the diagnosis and classification of the status of
      Alzheimer's disease using data from an fMRI experiment.
AB  - The aim of this work is the development of a method to assist the diagnosis and
      classification of the status of Alzheimer's Disease (AD) using information that
      can be extracted from fMRI. The method consists of five stages: a) preprocessing
      of fMRI data to remove non-task related variability, b) modeling BOLD response
      depending on stimulus, c) feature extraction from fMRI data, d) feature selection
      and e) classification using the Random Forests (RF) algorithm. The proposed
      method is evaluated using data from 41 subjects (14 young adults, 14 non demented
      older adults and 13 demented older adults.

PMID- 19163695
TI  - Exploring interregional brain interactivity in temporal lobe epilepsy using
      partial correlation analysis of fMRI data.
AB  - Simultaneous recording of functional magnetic resonance imaging (fMRI) and
      electroencephalography (EEG) has been recently used to measure metabolic changes
      related to interictal spikes in temporal lobe epilepsy (TLE). Since blood oxygen
      level dependent (BOLD) responses have been often observed in extratemporal
      regions, we propose to explore interregional brain connectivity using a data
      driven method based on partial correlation analysis of fMRI data. This approach
      allows to extract informations about functional interactivity and to
      differentiate direct from mediated interactions. We demonstrated that this
      technique provides a deeper insight into the functional relationships between the
      areas involved in the generation of spikes in TLE.

PMID- 19163696
TI  - Subspace identification methods and fMRI analysis.
AB  - The main goal of this paper is to propose application of modern multidimensional
      systems identification algorithms of the subspace identification theory in the
      context of fMRI data analysis. The methods originated in 1990s in the field of
      process control and identification and yield robust linear model parameter
      estimates for systems with many inputs, outputs and states. Our ultimate goal is
      to establish an alternative to the DCM analysis procedure which would eliminate
      its main drawbacks, namely the need to pre-define the models structure. The paper
      discusses results based on simulated data provided by the DCM simulator in the
      SPM toolbox. Several scenarios are presented, with varying amount of noise and
      number of data samples.

PMID- 19163697
TI  - A non-voxel based feature extraction to detect cognitive states in fMRI.
AB  - Over the past few decades, Functional Magnetic Resonance Imaging (fMRI) has
      evolved into an important utilitarian tool for analyzing brain activity and
      detecting the cognitive states of a subject. The design and development of
      effective dimensionality reduction schema for the discovery of discriminatory
      features for cognitive state classification has become an area of vital interest
      toward enhanced decision support applications for patients with various brain
      disorders. In this paper, we present a unique non-voxel based approach using
      wavelet descriptor differentiation and principal components to extract unique
      features that reduce slice variability in fMRI data for the enhanced
      classification of cognitive states. The set of cognitive states that we attempt
      to classify are 'a person reading a sentence' and 'a person reading a picture.'
      The discovered feature vector is small and achieves significant classification
      accuracy using different classifiers and under different Regions of Interest
      (ROI) constraints. Experimental results using this study demonstrate the
      effectiveness of the approach when compared to previous voxel-based approaches.

PMID- 19163698
TI  - An indoor navigation system to support the visually impaired.
AB  - Indoor navigation technology is needed to support seamless mobility for the
      visually impaired. A small portable personal navigation device that provides
      current position, useful contextual wayfinding information about the indoor
      environment and directions to a destination would greatly improve access and
      independence for people with low vision. This paper describes the construction of
      such a device which utilizes a commercial Ultra-Wideband (UWB) asset tracking
      system to support real-time location and navigation information. Human trials
      were conducted to assess the efficacy of the system by comparing target-finding
      performance between blindfolded subjects using the navigation system for real
      time guidance, and blindfolded subjects who only received speech information
      about their local surrounds but no route guidance information (similar to that
      available from a long cane or guide dog). A normal vision control condition was
      also run. The time and distance traveled was measured in each trial and a point
      back test was performed after goal completion to assess cognitive map
      development. Statistically significant differences were observed between the
      three conditions in time and distance traveled; with the navigation system and
      the visual condition yielding the best results, and the navigation system
      dramatically outperforming the non-guided condition.

PMID- 19163699
TI  - Wireless transmission of neuronal recordings using a portable real-time
      discrimination/compression algorithm.
AB  - A design challenge of portable wireless neural recording systems is the tradeoff
      between bandwidth and power consumption. This paper investigates the compression
      of neuronal recordings in real-time using a novel discriminating Linde-Buzo-Gray
      algorithm (DLBG) that preserves spike shapes while filtering background noise.
      The technique is implemented in a low power digital signal processor (DSP) which
      is capable of wirelessly transmitting raw neuronal recordings. Depending on the
      signal to noise ratio of the recording, the compression ratio can be tailored to
      the data to maximally preserve power and bandwidth. The approach was tested in
      real and synthetic data and achieved compression ratios between 184:1 and 10:1.

PMID- 19163700
TI  - Single access point localisation for wearable wireless sensors.
AB  - Knowledge of a subject's location and motion throughout an environment is of
      significant use to in-home health monitoring and activity recognition systems.
      This work develops a method of tracking a subject's location using the radio
      frequency (RF) signals emanating from wearable wireless sensors. It differs from
      other RF location tracking work in that it utilises the hardware which would
      already be deployed in a biomedical monitoring application. This is achieved by
      combining the RSSI (Received Signal Strength Indicator) and LQI (Link Quality
      Indicator) readings from a single basestation. It is shown that accuracy
      approaching that of a multiple basestation localisation deployment is achievable
      by using a suitable level of filtering. As a result of this work, location
      information can be more readily and cheaply incorporated into future biomedical
      monitoring applications.

PMID- 19163701
TI  - Active monitoring insole: a wearable device for monitoring foot load distribution
      in home-care context.
AB  - Post surgical patients need to resume a correct load distribution over both legs
      in order to facilitate bone osteogenesis. We propose a device for continuously
      monitoring lower limbs loads. It can be used by the patient to be aware of his
      loading conditions, by the physician or physical therapist to perform a
      quantitative analysis of applied loads. We tested the device on two subjects and
      verified its capability to detect reduced loads on the affected limb and its
      usefulness in helping to recognize in which walking phases.

PMID- 19163702
TI  - Advancing from offline to online activity recognition with wearable sensors.
AB  - Activity recognition with wearable sensors could motivate people to perform a
      variety of different sports and other physical exercises. We have earlier
      developed algorithms for offline analysis of activity data collected with
      wearable sensors. In this paper, we present our current progress in advancing the
      platform for the existing algorithms to an online version, onto a PDA.
      Acceleration data are obtained from wireless motion bands which send the 3D raw
      acceleration signals via a Bluetooth link to the PDA which then performs the data
      collection, feature extraction and activity classification. As a proof-of
      concept, the online activity system was tested with three subjects. All of them
      performed at least 5 minutes of each of the following activities: lying, sitting,
      standing, walking, running and cycling with an exercise bike. The average second
      by-second classification accuracies for the subjects were 99%, 97%, and 82 %.
      These results suggest that earlier developed offline analysis methods for the
      acceleration data obtained from wearable sensors can be successfully implemented
      in an online activity recognition application.

PMID- 19163703
TI  - Non-contact Heartbeat Sensor using LC oscillator circuit.
AB  - This paper proposes non-contact heartbeat sensor using LC oscillator for personal
      healthcare. The signals from chest and wrist are measured using LC oscillator and
      electrodes. The proposed sensor can detect human heartbeat signal without direct
      contact to skin and is readily a portable heartbeat monitoring sensor. The
      capacitive and inductive electrodes are addressed, which are key elements of the
      sensor circuit.

PMID- 19163704
TI  - Real-time 3D image-guided HIFU therapy.
AB  - Real-time three-dimensional ultrasound imaging (4D US) was utilized to monitor
      the treatment site during high-intensity focused ultrasound (HIFU) treatment. To
      obtain real-time monitoring during HIFU sonication, a 4D US imaging system and
      HIFU were synchronized and interference on the US image adjusted so that the
      region of interest was visible during treatment. The system was tested using
      tissue mimicking phantom gels and chicken breast tissue. The 4D US showed
      hyperechoic spots at the focal region of the HIFU transducer which then slowly
      faded after HIFU treatment. The hyperechoic regions were used as an indication of
      coagulative necrosis which occurs at temperatures higher than 60 degrees C.
      Different intensities of HIFU were applied to observe the difference in lesion
      formation and to determine the threshold intensity that produced hyperechoic
      regions due to the thermal and mechanical effects of focused ultrasound waves.
      The position, orientation, and shape of various lesions were examined in the
      three dimensional ultrasound images, and the volume of the lesions was measured.
      These volumes were compared to the volume measurements obtained from dissection
      of the tissue and phantom gels.

PMID- 19163705
TI  - Observing ultrasound stimulated microbubble dynamics at MHz framing rates.
AB  - Microbubble contrast agents were originally developed to enhance echogenicity in
      diagnostic sonography. However, their somewhat unique acoustic response and
      facility to transduct energy into spatially focussed regimes, together with the
      clinical demand for non-invasive adjuncts and options to conventional therapy,
      have seen interest in exploring the therapeutic potential of microbubbbles grow
      steadily within this past decade. For the purposes of the present study, we
      examined the ultrasonically stimulated response of many such microbubbles by
      controlling their spatial placement with bespoke optical traps. The objective was
      to improve our understanding of their statistical behaviour and to feed this
      information into realistic computational models so that processes might be more
      easily optimised. Hence, individual microbubbles of commercial [low-index]
      ultrasound contrast agent were isolated from a parent population by selection
      using a Laguerre-Gaussian optical trap, and subsequently manipulated to
      controllable micrometer level displacements from a solid surface. This
      configuration was then insonated using a 60ms burst of 1MHz ultrasound at a
      nominal peak pressure of 6.5MPa, and the subsequent bubble dynamics recorded
      using ultra high speed micro-photography at microsecond temporal resolutions. Any
      resultant damage induced at the target surface was also observed and
      characterised using atomic force microscopy.

PMID- 19163706
TI  - Ultrasound histotripsy and the destruction of Escherichia coli biofilms.
AB  - Ultrasound histotripsy has shown great potential for replacing surgery in many
      applications. In this work, a modification of ultrasound histotripsy was used to
      destroy Escherichia coli (E. coli) biofilms that had been grown on chambered
      microscope slides. Biofilms are central to the pathogenesis and persistence of
      nosocomial (hospital-acquired) infections associated with indwelling medical
      devices. The slides were exposed to 9.1 micros pulses at a pulse repetition
      frequency of 1000 Hz. The pulses were generated by a 1.1 MHz spherically focused
      source with a focal length of 6.3 cm and an active diameter of 7 cm. The peak
      rarefactional pressure for the pulses was varied as 3.1, 4.1, 5.2, 6.2, and 7.6
      MPa in addition to a sham where the biofilms were not exposed. The effectiveness
      of the treatment was assessed by determining the viable number of colony forming
      units (CFU) remaining in the biofilm. Most of the biofilms treated at the higher
      exposures of 6.2 and 7.6 MPa had no remaining CFU indicating that the biofilm was
      completely destroyed. However, the persistence of some CFU for some of the
      biofioms at the higher exposure settings needs to be resolved prior to
      implementing the treatment clinically.

PMID- 19163707
TI  - Therapy planning and monitoring of tissue ablation by high intensity focused
      ultrasound (HIFU) using imaging and simulation.
AB  - High intensity focused ultrasound (HIFU) 'cooks' or ablates the target tissue at
      the focus of the ultrasound beam by thermal and cavitation effects. The HIFU is
      emerging as a non-invasive method for tumor ablation. The HIFU application for
      tissue ablation requires tools for dosimetry therapy planning, and real-time
      feedback of the intended and actual target tissues. Pretreatment planning is an
      important step for a successful HIFU therapy outcome. Typically, the therapy
      planning approach involves the use of pretreatment imaging data, defining the
      target and surrounding tissues by manual or semiautomatic segmentation,
      development of a 3-D anatomy model of the region of interest from segmentation or
      registration with a reference dataset, simulation of the HIFU beam and thermal
      dosimetry around the target tissue, display and 3-D visualization of imaging and
      simulation data, and review of the treatment plan options. Recent developments in
      therapy planning using imaging are targeted for specific applications such as
      prostate cancer using 3-D ultrasound images and uterine fibroids using MRI.
      However, significant developments have been accomplished in image guidance and
      feedback during the delivery of HIFU treatments. This talk reviews recent work
      towards therapy planning and presents approaches for developing strategies for
      HIFU therapy. It describes general and target-specific techniques and software
      tools for HIFU treatment planning using pretherapy imaging, and monitoring and
      controlling the HIFU delivery and tissue lesion using 1D, 2D and 3D ultrasound
      imaging. This aids development of optimized, high-precision HIFU applications for
      a controlled ablation of the target tumor. It also potentially reduces the
      overall treatment duration and exposure to non-target tissues.

PMID- 19163708
TI  - Ultrasound-enhanced drug and gene delivery: a review.
AB  - Optimization of drug and gene delivery is currently a topic of great interest.
      This optimization can be achieved via sitespecific (targeted) delivery,
      controlled drug release, and by finding ways to deliver more of the drug into
      tissues of interest (despite various barriers). Targeted delivery can serve to
      lower the required drug dose and minimize toxic side effects, which is crucial
      for the success of cancer chemotherapy. Controlled release of drugs can be
      advantageous in the management of chronic diseases such as diabetes and
      hypertension. In recent years, application of ultrasound in the enhancement of
      drug delivery, controlled drug release, and site-specific delivery has been a
      topic of extensive research. Ultrasound was shown to improve delivery of
      thrombolytic agents, anticancer drugs, genes, and macromolecules into different
      tissues. This enhancement is believed to be due mostly to cavitation activity and
      streaming. Specifically, ultrasound was previously used for controlled release of
      insulin through the skin, targeted gene transfection into cardiac cells, delivery
      of medications through blood-brain and eye barriers, treatment of stroke, etc.
      This review talk will cover recent developments in various areas of ultrasound
      enhanced drug and gene delivery.

PMID- 19163709
TI  - Mental task classification against the idle state: a preliminary investigation.
AB  - The motivation for this study was to obtain candidate electrode sites for use in
      online self-paced brain-computer interfaces and preliminary classification
      results for comparison to online tests. Six mental tasks were tested for
      classification against an idle state. Data representing the idle state was
      collected in association with active mental task data during each recording
      session. Features were extracted in two representations, band power and
      reflection coefficients. A sequential forward floating search algorithm was used
      to obtain prevailing electrode-feature pairs for each subject-task combination
      under two conditions: maximising classification accuracy and maximising mean
      trial accuracy. Methods used to select electrode-feature combinations are found
      to lead to differing electrode sites in a number of task-feature combinations. An
      across task prevalence towards electrodes positioned in the left frontal
      hemisphere is observed when maximising classification accuracy.

PMID- 19163710
TI  - A brain computer interface based on motion-onset VEPs.
AB  - In this article, a novel brain-computer interface (BCI) based on motion-onset
      visual evoked potentials (mVEP) is proposed. Examination on the spatio-temporal
      pattern of motion-onset VEPs showed that the amplitude of N2 and P2 components of
      mVEP, evoked by attended target, was significantly higher than that by unattended
      ones. The area of N2 and P2 component was used as features for classifying the
      offline data of a five-class BCI, achieving an average accuracy of 98.33% in five
      subjects.

PMID- 19163711
TI  - Model-based responses and features in Brain Computer Interfaces.
AB  - Novel model based features are introduced in the discrimination of motor imagery
      tasks using human scalp electroencephalography (EEG) towards the development of
      Brain Computer Interfaces (BCI). We have acquired human scalp EEG under open-loop
      and feedback conditions in response to cue-based motor imagery tasks. EEG
      signals, transformed into frequency specific bands such as mu, beta and movement
      related potentials, were used for feature extraction with the aim to discriminate
      tasks. Data were classified using features such as power spectrum and model-based
      parameters. Two different feature selection methods: stepwise and principal
      component analysis (PCA), were combined with linear discriminant analysis (LDA).
      Different training/validation criteria were applied for classification of task
      related features. Results show that the scalp EEG correlate of the imagery tasks
      of hands/toes/tongue movements under open-loop conditions and left/right hand
      movements under feedback conditions, can be well discriminated with
      classification errors below 20%. Model based techniques, which resulted in
      classification errors in the range of 2%-30%, have the potential to use advanced
      control systems theory in the development of BCI to achieve improved performance
      compared to the performance achieved by currently applied proportional control or
      filter algorithms.

PMID- 19163712
TI  - Adapting human-machine interfaces to user performance.
AB  - The goal of this study was to create and examine machine learning algorithms that
      adapt in a controlled and cadenced way to foster a harmonious learning
      environment between the user of a human-machine interface and the controlled
      device. In this experiment, subjects' high-dimensional finger motions remotely
      controlled the joint angles of a simulated planar 2-link arm, which was used to
      hit targets on a computer screen. Subjects were required to move the cursor at
      the endpoint of the simulated arm.

PMID- 19163713
TI  - Neuronal tuning in a brain-machine interface during Reinforcement Learning.
AB  - In this research, we have used neural tuning to quantify the neural
      representation of prosthetic arm's actions in a new framework of BMI, which is
      based on Reinforcement Learning (RLBMI). We observed that through closed-loop
      brain control, the neural representation has changed to encode robot actions that
      maximize rewards. This is an interesting result because in our paradigm robot
      actions are directly controlled by a Computer Agent (CA) with reward states
      compatible with the user's rewards. Through co-adaptation, neural modulation is
      used to establish the value of robot actions to achieve reward.

PMID- 19163714
TI  - Extraction of SSVEP signals of a capacitive EEG helmet for human machine
      interface.
AB  - The use of capacitive electrodes for measuring EEG eliminates the preparation
      procedure known from classical noninvasive EEG measurements. The insulated
      interface to the brain signals in combination with steady-state visual evoked
      potentials (SSVEP) enables a zero prep human machine interface triggered by brain
      signals. This paper presents a 28-channel EEG helmet system based on our
      capacitive electrodes measuring and analyzing SSVEPs even through scalp hair.
      Correlation analysis is employed to extract the stimulation frequency of the EEG
      signal. The system is characterized corresponding to the available detection time
      with different subjects. As demonstration of the use of capacitive electrodes for
      SSVEP measurements, preliminary online Brain-Computer Interface (BCI) results of
      the system are presented. Detection times lie about a factor of 3 higher than in
      galvanic EEG SSVEP measurements, but are low enough to establish a proper
      communication channel for Human Machine Interface (HMI).

PMID- 19163715
TI  - Survey of clinical engineering effectiveness in developing world hospitals:
      equipment resources, procurement and donations.
AB  - This paper presents preliminary findings of a study of clinical engineering
      effectiveness within developing world hospitals. To date, 169 responses have been
      collected from 43 countries, primarily from Africa, Latin America and Asia, with
      some representation from the Middle East and Eastern Europe as well. Data is
      presented on: 1) hospital and clinical engineering department profiles; 2) human
      and equipment resources; and 3) equipment procurement and donation processes,
      with a focus on the role of the clinical engineering department. This is the
      first study to collect and analyze data on the complexity and state of hospital
      equipment across the developing world; additionally it is the first to collect
      significant responses from Africa. Prior to this study, only 10 developing
      countries had been profiled in international studies.

PMID- 19163716
TI  - Electromagnetic interference to infusion pumps. Update2008 from GSM mobile
      phones.
AB  - Electromagnetic interference (EMI) to critical care medical devices has been
      reported by various groups. Previuos study demonstrated that infusion pumps are
      susceptible of false alarm buzzing and block of infusion, when exposed to various
      EMI sources. Aim of this paper is to investigate the changes in the risk of EMI
      from the estimates of our previous 2005 survey and to extend the EMI risk
      assessment to newer telecommunication products: DECT phones and WiFi terminals.
      With regards to GSM phones, compare to the results obtained in 2005, we observed
      a decrease in the rate of failure (from 58% to 30%). From our findings, the use
      of WiFi and DECT does not pose a real risk to infusion systems.

PMID- 19163717
TI  - In-House Monitoring of low back pain related disability (IMPAIRED).
AB  - Preventive care, healthcare management and a working population are areas of
      growing emphasis in industrialized countries. Recent exponential growth in
      technological developments has made developing wearable monitoring systems
      feasible. Chronic Low Back Pain (CLBP) is a leading cause of disability with
      staggering economic costs and severe psychological and social consequences. A
      principal issue is the assessment of LBP severity at a single point of time
      during clinic visits rather than through continuous monitoring. This paper
      presents the project In-House Monitoring of Low-Back-Pain Related Disability
      (IMPAIRED) which aims to design and develop a multi-sensor wearable prototype to
      monitor movement of the lumbar spine and pelvis, sleep disturbance (circadian
      rhythm), as well as muscle fatigue and activity pattern. We have identified
      relevant movements correlating to disability associated with LBP, evaluated the
      suitability of inertial sensors to monitor the expected range of movement and
      proposed a sensor placement map.

PMID- 19163718
TI  - A mobile robot therapist for under-supervised training with robot/computer
      assisted motivating systems.
AB  - Robot assisted therapy is a new and promising area in stroke rehabilitation and
      has shown to be effective in reducing motor impairment, but is a costly solution
      for home rehabilitation. High medical costs could be reduced if we could improve
      rehabilitation exercise in unsupervised environments such as the home. Hence,
      there is an augmented need for a cost effective rehabilitation system that can be
      used outside the clinic. This paper presents the design concept for an autonomous
      robotic assistant that is low-cost and effective in engaging the users while
      assisting them with therapy in any under-supervised area. We investigated how the
      robot assistant can support TheraDrive, our low-cost therapy system. We present
      the design methods and a case study demonstrating the arm and video collection
      system.

PMID- 19163719
TI  - Indicators to estimate radiographic film savings due to a PACS in a Mexican
      health institute.
AB  - The scope of this paper is to evaluate the impact of PACS implementation in
      radiographic film (RF) savings at the Imaging Department at the National
      Institute of Respiratory Diseases in Mexico City, considering both Computed
      Tomography (CT) and Computed Radiography (CR) modalities. The PACS at the INER
      was installed in 2006, and the CT and CR have been operating entirely digitally
      since then. Therefore, the document evaluate three different periods, before the
      arriving of the PACS (2005), during the PACS installation (2006) and after PACS
      (2007). A set of indicators were designed to measure and visualize the impact of
      the PACS in the RF savings. Two templates are provided to define and to apply
      each one of the indicators proposed.

PMID- 19163720
TI  - Theoretical optimization of usage of four-wheeled walker and body posture of
      elderly users for comfortable steady walking.
AB  - Usage of a four-wheeled walker and body posture of elderly users is optimized by
      a two-dimensional statics model for comfortable steady walking. Analytical
      results suggest that fundamentals of body posture for comfortable walking should
      be as upright as possible. However, usage of the walker varies with exercise
      capabilities of elderly users. Users with high capabilities should use a higher
      handgrip for maintaining upright posture. Stooping users with low capabilities
      should use a lower handgrip, should maintain an erect trunk as much as possible,
      and should push the handgrip downward by leaning their upper body on the walker.

PMID- 19163721
TI  - Reflex changes associated with anticipatory postural adjustments preceding
      voluntary arm movements in standing humans.
AB  - Dynamic changes in human stability, such as those induced by upper body
      movements, are preceded by anticipatory postural adjustments (APAs) in the rest
      of the body. We measured the excitability of the stretch reflex of the triceps
      surae muscle group during APAs associated with unilateral right arm raises in
      standing humans. Our results demonstrate that reflex excitability and underlying
      muscle activity are linked during the APA period, but that they differ in their
      relative timing. This supports the idea that reflexes are controlled
      independently of muscle activation.

PMID- 19163722
TI  - Accelerometer versus footswitch evaluation of gait unsteadiness and temporal
      characteristics of gait in two elderly patient groups.
AB  - We examined anterior-posterior and medio-lateral head and trunk movements during
      gait using accelerometers, and a footswitch evaluation of temporal gait
      parameters of elderly fallers with a primary diagnosis of Orthostatic
      Hypotension, elderly fallers without Orthostatic Hypotension, and a control group
      of healthy elderly non-fallers. We wanted to evaluate whether both sets of
      measures can be used to differentiate between patient groups. We were able to
      significantly differentiate between the three elderly groups to the same extent
      using both sets of measures.

PMID- 19163723
TI  - Video based analysis of standing balance in a community center.
AB  - Postural sway is a well known measure of postural stability in the elderly. Sway
      measurements, however, are typically made using expensive equipment in a
      laboratory. We report on efforts to make clinically significant and quantitative
      measurements of postural sway in a community center with a single un-calibrated
      video camera. Results indicate that simple tracking technologies can capture some
      aspects of sway in a community center in a way that is perceptually accurate and
      capable of distinguishing expert-assigned levels of balance performance in an
      elderly, balance impaired cohort.

PMID- 19163724
TI  - Application of a bi-planar postural stability model in children with cerebral
      palsy.
AB  - This study presents initial results from a bi-planar model used to investigate
      the neurological factors affecting balance deficits in children with diplegic
      cerebral palsy (CP). The model uses an inverted pendulum to describe sway in both
      the anteroposterior (AP) and mediolateral (ML) planes. The study presents Center
      of Pressure (COP) data from 17 children diagnosed with spastic diplegic CP using
      two standard AMTI force plates. Sway metrics in the time and frequency domains in
      the AP and ML planes were calculated and compared to simulations produced by the
      model. The proposed bi-planar model successfully reproduced sway signals acquired
      from experimental (clinical) data.

PMID- 19163725
TI  - Assessing the psychophysics of posture control and its physiological correlates.
AB  - Graphical visualization methods are described that enable psychophysical
      detection data to be quantitatively correlated with underlying physiological data
      in postural control studies. Stitched, raster and ensemble averaged time-series
      plots are graphical tools that can guide later quantitative analysis. The
      examples presented point out the role that early Tibialis Anterior and later
      Gastrocnemius EMG activation might play in the 2-Alternative Forced Choice
      psychophysical detection of 16 mm horizontal anterior perturbations of a sliding
      platform on which a subject stands, and their linkage to AP and ML Center of
      Pressure changes brought about by a perturbation. These methods also give a
      preliminary indication that differing or no response patterns were seen at 4 and
      1 mm.

PMID- 19163726
TI  - Noninvasive estimation of three-dimensional cardiac electrical activities from
      body surface potential maps.
AB  - A noninvasive three-dimensional (3D) cardiac electrical imaging (3DCEI) approach,
      which can estimate the location of the initiation site (IS) of activation and the
      resultant 3D activation sequence (AS) from body surface potential maps (BSPMs),
      was validated in an intact large mammalian model (swine) during acute ventricular
      pacing. Body surface potential mapping and intracavitary noncontact mapping (NCM)
      were performed simultaneously during pacing from both right ventricular (RV)
      sites (intramural) and left ventricular (LV) sites (endocardial). Subsequent
      3DCEI analyses were performed on the measured BSPMs. In total, 5 RV and 5 LV
      sites from control and heart failure animals were paced. The averaged
      localization error of the RV and LV sites were 7.0+/-1.1 mm and 6.6+/-1.9 mm,
      respectively. The endocardial ASs as a subset of the estimated 3D ASs by 3DCEI
      were consistent with those reconstructed from the NCM system. The present
      experimental results demonstrate that the noninvasive 3DCEI approach can localize
      the initiation site and estimate cardiac activation sequence with good accuracy
      in an in vivo setting, under control, paced and/or diseased conditions.

PMID- 19163727
TI  - Comparative analysis of temporal dynamics of EEG and phase synchronization of EEG
      to localize epileptic sites from high density scalp EEG interictal recordings.
AB  - Our objective was to examine if the high-density, 256 channel, scalp interictal
      EEG data can be used for localizing the epilepsy areas in patients. This was done
      by examining the long-range temporal correlations (LRTC) of EEGs and also that of
      the phase synchronization index (SI) of EEGs. It was found that the LRTC of scalp
      SI plots were better in localizing the seizure areas as compared with the LRTC of
      EEGs alone. The EEG data of one minute duration was filtered in the low Gamma
      band of 30-50 Hz. A detrended fluctuation analysis (DFA) was used to find LRTC of
      the scalp EEG data. Contour plots were constructed using a montage of the layout
      of 256 electrode positions. The SI was computed after taking Hilbert transform of
      the EEG data. The SI between a pair of channel was inferred from a statistical
      tendency to maintain a nearly constant phase difference over a given period of
      time even though the analytic phase of each channel may change markedly during
      that time frame. The SI for each electrode was averaged over with the nearby six
      electrodes. LRTC of the SI was computed and spatial plots were made. It was found
      that the LRTC of SI was highest at the location of the epileptic sites. A similar
      pattern was not found in the LRTC of EEGs. This provides a noninvasive way to
      localize seizure areas from scalp EEG data.

PMID- 19163728
TI  - Study of the time-varying cortical connectivity during the attempt of a foot
      movement by Spinal Cord Injured patients.
AB  - In this study we estimated time-varying cortical connectivity patterns from a
      group of Spinal Cord Injured (SCI) patients during the attempt to move a
      paralyzed limb. This data were compared with the time-varying connectivity
      patterns estimated in a control group during the effective execution of the
      movement. Connectivity was estimated from high resolution EEG recordings with the
      use of realistic head modelling and the linear inverse estimation of the cortical
      activity. Time-varying PDC was obtained by the adaptive recursive fit of an MVAR
      model with time-dependent parameters, by means of a generalized recursive least
      square (RLS) algorithm, taking into consideration a set of EEG epochs. Such
      estimator is able to follow rapid changes in the connectivity between cortical
      areas during an experimental task. The obtained experimental evidences support
      the conclusion that the SCI population involved a larger cortical network than
      those generated by the healthy subjects during the task performance. Such network
      differs for the involvement of the parietal cortices, which increases in strength
      near to the EMG onset.

PMID- 19163729
TI  - A novel sparse source imaging in reconstructing extended cortical current
      sources.
AB  - We have developed a new sparse source imaging (SSI) method with the use of the L1
      norm in EEG inverse problems to reconstruct extended cortical current sources.
      The new SSI method explores the sparseness in cortical current density variation
      maps (the transform domain) other than in the cortical current density maps (the
      original domain) from previously reported SSI methods. The new SSI is assessed by
      a series of computer simulations. The performance of SSI is compared with the
      well-known L2-norm MNE using the AUC metric. Our present simulation data indicate
      that the new SSI has significantly improved performance in reconstructing
      extended cortical current sources and estimating their cortical extents. The L2
      norm MNE shows relatively poor performance in the same source imaging tasks. The
      new SSI method is also applicable to MEG source imaging.

PMID- 19163730
TI  - Preliminary imaging results of magnetic induction tomography based on physical
      phantom.
AB  - Magnetic induction tomography (MIT) is a kind of contactless and noninvasive
      method to reconstruct the conductivity distribution in a cross-section. We
      developed a data acquisition system with one exciting coil and 15 measuring
      coils. By rotating the object placing on a circle plate, the 16*15 measurement
      data were obtained. The Newton-Raphson algorithm was applied to reconstruct the
      conductivity distribution. To the conductivity perturbation objects in air field,
      we made the difference images of MIT. The images were able to demonstrate the
      location of the objects and identify the conductivity difference between 0.84 S/m
      and 1.26 S/m, which are in the range of biological tissue.

PMID- 19163731
TI  - The effect of tissue anisotropy on the EEG inverse problem.
AB  - Electroencephalogram (EEG) source analysis is typically done using head models
      with isotropic tissue conductivities. This ignores the fact that some tissues are
      known to be highly anisotropic. In this study, we investigate the effect that
      tissue anisotropy has on the EEG inverse problem. EEG electrode voltages are
      simulated using the forward problem solution for an anisotropic head model, while
      the inverse problem is solved for an isotropic head model. The error associated
      with neglecting anisotropy is quantified with the source localization error. A
      realistic head model is generated from magnetic resonance images and anisotropic
      conductivity values are estimated from diffusion tensor images. All calculations
      are done with the finite volume method on a cubic grid with 1 mm resolution. We
      determine that neglecting to account for anisotropy can cause considerable source
      localization errors, indicating that the anisotropic conductivities should not be
      ignored in EEG source analysis.

PMID- 19163732
TI  - Towards predicting biomechanical consequences of jaw reconstruction.
AB  - We are developing dynamic computer models of surgical jaw reconstructions in
      order to determine the effect of altered musculoskeletal structure on the
      biomechanics of mastication. We aim to predict post-reconstruction deficits in
      jaw motion and force production. To support these research goals we have extended
      our biomechanics simulation toolkit, ArtiSynth [1], with new methods relevant to
      surgical planning. The principle features of ArtiSynth include simulation of
      constrained rigid-bodies, volume-preserving finite-element methods for deformable
      bodies, contact between bodies, and muscle models. We are adding model editing
      capabilities and muscle activation optimization to facilitate progress on post
      surgical simulation. Our software and research directions are focused on upper
      airway and cranio-facial anatomy, however the toolset and methodology are
      applicable to other musculoskeletal systems.

PMID- 19163733
TI  - Development of a knee joint motion simulator to evaluate deep knee flexion of
      artificial knee joints.
AB  - A purpose of this study is to examine the effect that quadriceps femoris force
      gives to rotation angle and joint reaction force of total knee prosthesis during
      deep knee flexion such as a unique sitting style called 'seiza' in Japanese. For
      the evaluation, we developed the knee motion simulator which could bend to 180
      degrees continually simulating the passive flexion performed by clinicians. A
      total knee prosthesis, which is a specially-devised posterior stabilized type and
      capable of flexion up to 180 degrees, was inserted into bone model. And this
      prosthesis pulled by three kinds of quadriceps femoris forces to perform
      parameter study. The results obtained in this study were showed the same tendency
      with those in the past cadaveric experiment. It is suggested that the rotation
      angle and joint reaction force of total knee prosthesis are affected by shape of
      prosthesis, a vector of quadriceps femoris force, and bony aliments during deep
      knee flexion.

PMID- 19163734
TI  - Motion capture based identification of the human body inertial parameters.
AB  - Identification of body inertia, masses and center of mass is an important data to
      simulate, monitor and understand dynamics of motion, to personalize
      rehabilitation programs. This paper proposes an original method to identify the
      inertial parameters of the human body, making use of motion capture data and
      contact forces measurements. It allows in-vivo painless estimation and monitoring
      of the inertial parameters. The method is described and then obtained
      experimental results are presented and discussed.

PMID- 19163735
TI  - Benchmarking of a full-body inertial motion capture system for clinical gait
      analysis.
AB  - In order for gait analysis to be established as part of routine clinical
      diagnoses, an accurate, flexible and user-friendly motion capture system is
      required. Commonly used optical, mechanical and acoustic systems offer acceptable
      accuracy and repeatability, but are often expensive and restricted to laboratory
      use. Inertial motion capture has seen great innovation in the last few years, but
      the technology is not yet considered mature enough for clinical gait analysis. In
      this paper we compare the kinematic reliability of inertial motion capture with
      optical motion capture during routine gait studies of eight able-bodied subjects.
      The root mean squared, RMS, and coefficient of correlation, R, was used to
      compare data sets. Saggital plane joint angles in the knee and hip compared very
      well. Corresponding transverse and frontal plane values were moderately accurate.
      The ankle joint angles calculated from the two systems were less accurate. This
      was believed to be due to the use of different rotation axis orientations used
      for calculation of angular rotations.

PMID- 19163736
TI  - Upper extremity kinetics of children with myelomeningocele during Lofstrand
      crutch-assisted gait.
AB  - The use of quantitative methods for evaluating upper extremity (UE) dynamics in
      children with myelomeningocele (MM) is currently limited. We present a novel
      biomechanical model for assessment of UE dynamics during Lofstrand (forearm)
      crutch-assisted gait with application in 9 children with MM. Two prominent types
      of forearm, crutch-assisted gait patterns were studied: 1) reciprocal gait (RG)
      and 2) swing-through gait (STG). The model demonstrated the ability to
      successfully detect meaningful differences in wrist, elbow, shoulder and crutch
      dynamics in the population of 9 children tested. Significant differences in
      kinetics with reciprocal and swing-through gait patterns were found bilaterally
      at all joints. Notable differences were found in the mean superior/inferior joint
      forces, ranges of joint force, and maximum inferior joint forces. Accurate
      quantitative assessment may help to prevent injury from longer-term crutch use
      and has the potential for improving clinical intervention and therapeutic
      management of ambulation in children with MM.

PMID- 19163737
TI  - An accurate and robust gyroscope-gased pedometer.
AB  - Pedometers are known to have steps estimation issues. This is mainly attributed
      to their innate acceleration based measuring sensory. A micro-machined gyroscope
      (better immunity to acceleration) based pedometer is proposed. Through syntactic
      data recognition of apriori knowledge of human shank's dynamics and temporally
      precised detection of heel strikes permitted by Wavelet decomposition, an
      accurate and robust pedometer is acquired.

PMID- 19163738
TI  - A method for evaluating effects of visually-induced motion sickness using ICA for
      photoplethysmography.
AB  - A human watching a swaying image displayed on a wide-field display or screen
      sometimes suffers from visually-induced motion sickness (VIMS) that causes
      symptoms related to the autonomic nervous system such as nausea, vomiting, and
      dizziness. Previous studies indicated that the maximum cross-correlation
      coefficient (rho(max)) between blood pressure and heart rate, whose frequency
      components were limited to the neighborhood of 0.1Hz, was a useful index to
      evaluate the effects of VIMS on humans. The present study proposed a new method
      for obtaining rho(max) with measurement of neither continuous blood pressure nor
      ECG but using only finger photoplethysmography (PPG). In this study, heart rate
      was obtained from the foot-to-foot-interval of the PPG signal, and blood pressure
      related and event-related pieces of information were obtained from the parameter
      extracted from using the independent component analysis. The adequacy of the
      proposed method was evaluated by two experiments with the Valsalva maneuver and
      with presentation of a swaying video image. The experimental results have shown
      that the proposed method could extract the independent component related to blood
      pressure and an event signal of Valsalva maneuver. In addition, the effects of
      VIMS could be estimated with the independent component.

PMID- 19163739
TI  - Interpolation of the subjective score of visually-induced motion sickness by
      using physiological parameters.
AB  - In order to investigate the effect of visually-induced motion sickness in actual
      video images, this study proposes a method of interpolation for the subjective
      score, which has low time and quantitative resolutions, by using physiological
      parameters. The model which represents the change in subjective score of VIMS was
      expressed as multiple regression equations in which input parameters are
      cardiovascular indices such as heart rate variability. The estimation results
      indicated that the model can represent, in higher resolution, the change in the
      subjective score of the subjects who have induced nausea.

PMID- 19163740
TI  - Integrated evaluation of visually induced motion sickness in terms of autonomic
      nervous regulation.
AB  - To evaluate visually-induced motion sickness, we integrated subjective and
      objective responses in terms of autonomic nervous regulation. Twenty-seven
      subjects viewed a 2-min-long first-person-view video section five times (total 10
      min) continuously. Measured biosignals, the RR interval, respiration, and blood
      pressure, were used to estimate the indices related to autonomic nervous activity
      (ANA). Then we determined the trigger points and some sensation sections based on
      the time-varying behavior of ANA-related indices. We found that there was a
      suitable combination of biosignals to present the symptoms of visually-induced
      motion sickness. Based on the suitable combination, integrating trigger points
      and subjective scores allowed us to represent the time-distribution of subjective
      responses during visual exposure, and helps us to understand what types of camera
      motions will cause visually-induced motion sickness.

PMID- 19163741
TI  - Reliability of cluster results for different types of time adjustments in complex
      disease research.
AB  - We aim to identify subtypes of diseases like Osteoarthritis (OA) and Parkinson's
      Disease (PD) that present clinical heterogeneity. We do so by searching for
      homogeneous clusters in values of markers that reflect the severity of the
      disease. In the current paper we consider two important items for a cluster
      analysis. First, as time can contribute largely to the measured variability in
      the data, we search for the most appropriate way to adjust for it. Second, as we
      aim for reliable cluster analyses, cluster results should exhibit robustness to
      little change in the data. To investigate these issues, we transform the data by
      adding noise of different levels before cluster modeling and we rely on a chi(2)
      based measure of association to compare cluster results for different types of
      time adjustment. The results of our experiments suggest to adjust data for a
      logarithmic age effect for OA and a square root effect of the disease duration
      for PD because these adjustments lead more reliable cluster results.

PMID- 19163742
TI  - Complimentary artificial neural network approaches for prediction of events in
      the neonatal intensive care unit.
AB  - In the neonatal intensive care unit, the early and accurate prediction of
      mortality, length of stay and duration of ventilation can improve decision
      making. For physiological events, non-linear prediction models generally out
      perform statistical-based approaches, as was confirmed in these experiments. For
      three medical outcomes, the maximum-likelihood (ML) approximation was used in
      conjunction with a gradient descent artificial neural network (ANN) prototype to
      create models with risk estimation ranges. The ML ANN showed that the ML
      estimation function was successful at creating variable sensitivity models for
      three important outcomes. The flexibility of the ML ANN in terms of output values
      differentiates it from the more traditional ANN.

PMID- 19163743
TI  - Analysis of postprandial lipemia as a Cardiovascular Disease risk factor using
      genetic and clinical information: an Artificial Neural Network perspective.
AB  - Clinical studies indicate that exaggerated postprandial lipemia is linked to the
      progression of atherosclerosis, leading cause of Cardiovascular Diseases (CVD).
      CVD is a multi-factorial disease with complex etiology and according to the
      literature postprandial Triglycerides (TG) can be used as an independent CVD risk
      factor. Aim of the current study is to construct an Artificial Neural Network
      (ANN) based system for the identification of the most important gene-gene and/or
      gene-environmental interactions that contribute to a fast or slow postprandial
      metabolism of TG in blood and consequently to investigate the causality of
      postprandial TG response. The design and development of the system is based on a
      dataset of 213 subjects who underwent a two meals fatty prandial protocol. For
      each of the subjects a total of 30 input variables corresponding to genetic
      variations, sex, age and fasting levels of clinical measurements were known.
      Those variables provide input to the system, which is based on the combined use
      of Parameter Decreasing Method (PDM) and an ANN. The system was able to identify
      the ten (10) most informative variables and achieve a mean accuracy equal to
      85.21%.

PMID- 19163744
TI  - Quantitative metrics for bio-modeling algorithm selection.
AB  - In this paper, we report our efforts in developing guidelines that are capable of
      helping researchers to select algorithms in systems biology modeling. We propose
      a set of metrics based on discrete observable units in terms of key bio-modeling
      considerations. We accomplish this by (i) reviewing classical metric definitions,
      (ii) implementing widely used modeling algorithms on a specific case study, and
      (iii) testing metrics that are a hybrid of classical metrics and key bio-modeling
      considerations. The modeling algorithms implemented are Michaelis-Menten
      kinetics, generalized mass action, flux balance analysis, and metabolic control
      analysis. This work extends our previous work in developing qualitative
      guidelines to select bio-modeling algorithms. Our results impact systems biology
      modeling specifically by increasing the level of confidence for users to select
      bio-modeling algorithms by using quantitative metrics appropriately.

PMID- 19163745
TI  - Learning brain connectivity with the false-discovery-rate-controlled PC
      algorithm.
AB  - Discovering the connectivity networks in the brain, i.e. the neural influence
      that brain regions exert over one another, has attracted increasing research
      attention in studies on brain functions. An important error rate criterion on the
      discovered network is the false discovery rate (FDR), that is the expected ratio
      of the falsely 'discovered' connections to all those 'discovered'. Very recently,
      we have developed an algorithm that is able to control the FDR under a given
      level q at the limit of large sample size, and its modification that controlled
      the FDR accurately in simulations with moderate sample sizes [1]. However, the
      algorithms do not consider prior knowledge on the network structure, and can not
      be applied to models such as dynamic Bayesian networks. In this paper, we extend
      the algorithms to incorporate prior knowledge, and demonstrate how to apply the
      extended algorithm to learning the structure of dynamic Bayesian networks from
      continuous data. Its application to a real functional-Magnetic-Resonance-Imaging
      (fMRI) data set revealed that Parkinson's disease patients' brain connectivities
      are normalized by L-dopa medication. This result is consistent with the fact that
      L-dopa has dramatic effects against bradykinesia and rigidity.

PMID- 19163746
TI  - Implicit methods for probabilistic modeling of Gene Regulatory Networks.
AB  - In silico modeling of Gene Regulatory Networks (GRN) has recently aroused a lot
      of interest in the biological community for modeling and understanding complex
      pathways. Boolean Networks (BN) are a common modeling tool for in silico dynamic
      analysis of such pathways. Although they are known to have effectively modeled
      many real and complex regulatory networks, they are deterministic in nature and
      have shortcomings in modeling non-determinism that is inherent in biological
      systems. Probabilistic Boolean Networks (PBN) have been proposed to counter these
      shortcomings. The capabilities of PBNs have been so far under-utilised because of
      the lack of an efficient PBN toolbox. This work addresses some issues associated
      with traditional methods of PBN representation and proposes efficient algorithms
      to model gene regulatory networks using PBNs.

PMID- 19163747
TI  - An acoustic fall detector system that uses sound height information to reduce the
      false alarm rate.
AB  - More than one third of about 38 million adults 65 and older fall each year in the
      United States. To address the above problem we propose to develop an acoustic
      fall detection system (FADE) that will automatically signal a fall to the
      monitoring caregiver. As opposed to many existent fall detection systems that
      require the monitored person to wear devices such as accelerometers or gyroscopes
      at all times, our system is completely unobtrusive by not requiring any wearable
      devices. To reduce the false alarm rate we employ an array of acoustic sensors to
      obtain sound source height information. The sound is considered a false alarm if
      it comes from a source located at a height higher than 2 feet. We tested our
      system in a pilot study that consisted of a set of 23 falls performed by a stunt
      actor during six sessions of about 15 minutes each (1.3 hours in total). The
      actor was previously trained by our nursing collaborators to fall like an elderly
      person. The use of height information reduced the false alarm hourly rate from 32
      to 5 at a 100% fall detection rate.

PMID- 19163748
TI  - Fall detection of elderly through floor vibrations and sound.
AB  - Falls are very prevalent among the elderly especially in their home. The
      statistics show that approximately one in every three adults 65 years old or
      older falls each year. Almost 30% of those falls result in serious injuries.
      Studies have shown that the medical outcome of a fall is largely dependent upon
      the response and rescue time. Therefore, reliable and immediate fall detection
      system is important so that adequate medical support could be delivered. We have
      developed a unique and inexpensive solution that does not require subjects to
      wear anything. The solution is based on floor vibration and acoustic sensing, and
      uses a pattern recognition algorithm to discriminate between human or inanimate
      object fall events. Using the proposed system we can detect human falls with a
      sensitivity of 95% and specificity of 95%.

PMID- 19163749
TI  - Dual-microphone Sounds of Daily Life classification for telemonitoring in a noisy
      environment.
AB  - Telemonitoring of elderly people in their homes using video cameras is
      complicated by privacy concerns, and hence sound has emerged as a promising
      alternative that is more acceptable to users. We investigate methods to address
      the accuracy degradation of sound classification that arises in the presence of
      background noise typical of a practical telemonitoring situation. A dual
      microphone configuration is used to record a database of Sounds of Daily Life
      (SDL) in a kitchen. We introduce a new algorithm employing the eigenvalues of the
      cross-spectral matrix of the recorded signals to detect the endpoints of a SDL in
      the presence of background noise. Independent component analysis is also used to
      improve the signal to noise ratio of the SDL. Results on a 7-class noisy SDL
      classification problem show that the error rate the proposed SDL classification
      system can be improved by up to 97% relative to a single-microphone system
      without noise reduction techniques, when evaluated on a large SDL database with
      SNRs in the range 0-28 dB.

PMID- 19163750
TI  - Real time sound analysis for medical remote monitoring.
AB  - The increase of aging population in Europe involves more people living alone at
      home with an increased risk of home accidents or falls. In order to prevent or
      detect a distress situation in the case of an elderly people living alone, a
      remote monitoring system based on the sound environment analysis can be used. We
      have already proposed a system which monitors the sound environment, identifies
      everyday life sounds and distress expressions in order to participate to an alarm
      decision. This first system uses a classical sound card on a PC or embedded PC
      allowing only one channel monitor. In this paper, we propose a new architecture
      of the remote monitoring system, which relies on a real time multichannel
      implementation based on an USB acquisition card. This structure allows monitoring
      eight channels in order to cover all the rooms of an apartment. More than that,
      the SNR estimation leads currently to the adaptation of the recognition models to
      environment.

PMID- 19163751
TI  - Sound and speech detection and classification in a Health Smart Home.
AB  - Improvements in medicine increase life expectancy in the world and create a new
      bottleneck at the entrance of specialized and equipped institutions. To allow
      elderly people to stay at home, researchers work on ways to monitor them in their
      own environment, with non-invasive sensors. To meet this goal, smart homes,
      equipped with lots of sensors, deliver information on the activities of the
      person and can help detect distress situations. In this paper, we present a
      global speech and sound recognition system that can be set-up in a flat. We
      placed eight microphones in the Health Smart Home of Grenoble (a real living flat
      of 47m(2)) and we automatically analyze and sort out the different sounds
      recorded in the flat and the speech uttered (to detect normal or distress french
      sentences). We introduce the methods for the sound and speech recognition, the
      post-processing of the data and finally the experimental results obtained in real
      conditions in the flat.

PMID- 19163752
TI  - Learning diagnostic models using speech and language measures.
AB  - We describe results that show the effectiveness of machine learning in the
      automatic diagnosis of certain neurodegenerative diseases, several of which alter
      speech and language production. We analyzed audio from 9 control subjects and 30
      patients diagnosed with one of three subtypes of Frontotemporal Lobar
      Degeneration. From this data, we extracted features of the audio signal and the
      words the patient used, which were obtained using our automated transcription
      technologies. We then automatically learned models that predict the diagnosis of
      the patient using these features. Our results show that learned models over these
      features predict diagnosis with accuracy significantly better than random. Future
      studies using higher quality recordings will likely improve these results.

PMID- 19163753
TI  - Spatiotemporal group ICA applied to fMRI datasets.
AB  - Exploratory data analysis techniques such as independent component analysis (ICA)
      do not depend on a priori hypotheses and are able to detect unknown, yet
      structured spatiotemporal processes in neuroimaging data. We present fMRI data of
      two different subject-groups (young and old), which performed a modified
      Wisconsin Card Sorting Test (WCST). Spatiotemporal ICA and SPM-generated brain
      maps of the subject data are compared. For the group analysis a singular value
      decomposition approach was used. Spatiotemporal ICA reveals a frontoparietal
      network being activated while subjects performed different variants of the WCST.
      Contrary to the SPM analysis, ICA analysis revealed significant differences
      between young and old subjects as well as significant within-group
      differences.While young subjects showed with increasing task demands (A>>B>>C)
      increasing activation of the right lateral prefrontal cortex and of the medial
      orbito-frontal cortex, old subjects showed no such gradient in activation pattern
      and appeared to be more distributed.

PMID- 19163754
TI  - EOG artifact minimization using oblique projection corrected eigenvector
      decomposition.
AB  - In this paper, the authors propose an efficient algorithm to minimize the
      electrooculogram (EOG) artifacts in electroencephalogram (EEG). The approach uses
      the eigenvectors obtained from a learning process to initialize an oblique
      projection based blind source extraction (BSE) algorithm. It is used to extract
      the point source EOG artifacts. EEG data is subsequently reconstructed by a
      deflation method. The simulations with synthetic data illustrate that the BSE
      corrected algorithm is reliable and has better performance than the uncorrected
      eigenvector decomposition based method. The results of simulations with real EEG
      data confirms the effectiveness of our algorithm.

PMID- 19163755
TI  - An offline auditory P300 brain-computer interface using principal and independent
      component analysis techniques for functional electrical stimulation application.
AB  - A brain-computer interface (BCI) provides technology that allows communication
      and control for people who are unable to interact with their environment. A P300
      BCI exploits the fact that external or internal stimuli may provide a recognition
      response in the brain's electrical activity which may be recorded by an
      electroencephalogram (EEG) to act as a control signal. Additionally an auditory
      BCI does not require the user to avert their visual attention away from the task
      at hand and is thus more practical in a real environment than other visual
      stimulus BCIs.

PMID- 19163756
TI  - ICA analysis of retina images for glaucoma classification.
AB  - Glaucoma represent one of the most frequent causes of partial loss of the visual
      field. It comes along with an ongoing destruction of the optic nerve caused by an
      increased pressure of the eye liquid. The disease becomes obvious from
      investigations of the retina with scanning laser microscopes. In this report an
      image analysis and classification system based on independent component analysis
      and k-nearest-neighbor classification is proposed. The method is tested with 120
      selected retina images collected with the Heidelberg Retina Tomograph and
      achieves a classification rate of 91%.

PMID- 19163757
TI  - On the selection of the cost function for gradient-based decomposition of surface
      electromyograms.
AB  - Recently, gradient Convolution Kernel Compensation method was introduced for
      blind assessment of sparse pulse sequences (PS) out of their convolutive
      mixtures. This method employs multichannel recordings, is fully automatic and is
      minimally biased by assumptions about underlying mixing process. In the first
      step, the unknown mixing channels (convolution kernels) are compensated, whereas
      in the second step the gradient algorithm is used to blindly optimize the
      estimated PSs. This paper discusses the selection of the cost functions for
      aforementioned gradient-based optimization and provides analytical framework for
      their mutual comparison. Theoretical derivations are validated on both synthetic
      signals with random mixing matrices and experimental surface electromyograms from
      abductor pollicis brevis muscle. The analytical derivations agree very well with
      the results obtained from numerical simulations and establish theoretical
      guidelines for developing new gradient-based decomposition methods.

PMID- 19163758
TI  - Classification of Parkinson gait and normal gait using Spatial-Temporal Image of
      Plantar pressure.
AB  - The purpose of this paper is the classification of Spatial-Temporal Image of
      Plantar pressure (STIP) among normal step and the patients step of Parkinson
      disease. For this, we created a new image data, STIP, that have information of
      the change of plantar pressure during heel to toe motion (i.e., contain spatial
      and temporal information for plantar pressure). To get STIP, the walking of 21
      patients with Parkinson disease and 17 age-matched healthy subjects were recorded
      and analyzed using in-shoe dynamic pressure measuring system with comfort
      walking. For feature extraction of gait, we applied Principal component analysis
      (PCA) to STIP and calculated weights of STIP on each principal components. Then,
      we build hard margin Support Vector Machine (SVM) classifier for gait recognition
      and test of generalization performance using normalized weights on PCs of STIP.
      SVM result indicated an overall accuracy of 91.73% by the RBF(Radial Basis
      Function) kernel function. These results demonstrate considerable potential in
      applying SVMs in gait classification for many applications.

PMID- 19163759
TI  - A new fuzzy support vectors machine for biomedical data classification.
AB  - In this paper a new approach to a fuzzy support vector machine (FSVM) for solving
      multi-class problems is presented. The developed algorithm combines two separate
      methods based on fuzzy support vector machine, one for solving two-class problems
      and the second for multi-class problems. The first method deals with the problem
      of selecting the best support vector machine (SVM) kernel function and the second
      method enables classification of unclassified regions that appear when classical
      SVM methods for solving multi-class problems are used. Presented tool has been
      subjected to the dataset from Kent Ridge Biomedical Data Set Repository and
      showed its superiority comparing with conventional SVM and FSVM methods.

PMID- 19163760
TI  - Discrete wavelet transform for analysis of spike-wave discharges in rats.
AB  - In this paper, the discrete wavelet transform (DWT) as a feature extraction
      method was used in representing the spike-wave discharges (SWD) records of
      WAG/Rij rats. The SWD records of WAG/Rij rats were decomposed into time-frequency
      representations using the DWT and the statistical features were calculated to
      depict their distribution. The obtained wavelet coefficients were used to
      identify characteristics of the signal that were not apparent from the original
      time domain signal. The present study demonstrates that the wavelet coefficients
      are useful in determining the dynamics in the time-frequency domain of SWD
      records.

PMID- 19163761
TI  - A heuristic method for finding the optimal number of clusters with application in
      medical data.
AB  - In this paper, a heuristic method for determining the optimal number of clusters
      is proposed. Four clustering algorithms, namely K-means, Growing Neural Gas,
      Simulated Annealing based technique, and Fuzzy C-means in conjunction with three
      well known cluster validity indices, namely Davies-Bouldin index, Calinski
      Harabasz index, Maulik-Bandyopadhyay index, in addition to the proposed index are
      used. Our simulations evaluate capability of mentioned indices in some artificial
      and medical datasets.

PMID- 19163762
TI  - A novel shape analysis technique for somatosensory evoked potentials.
AB  - Somatosensory evoked potentials (SEP) have been shown to be an important
      electrophysiological measure to assess the integrity of the spinal cord. However
      the peaks in the SEP waveform are often undetectable due to low signal-to-noise
      (SNR) ratio. Sometimes they also become indistinct during injury when the SEP
      flattens. Hence time-domain analysis methods are often subject to errors, and
      need human-expert intervention. In this paper, we propose a new technique for
      analyzing the shape of the evoked potentials, in which slope information is
      obtained for the entire signal in specific time bins. Apart from solving the
      problems associated with present methods, this technique has an added advantage
      of analyzing the SEP signal as a whole rather than simply a few peaks. The
      efficacy of this technique was investigated on SEP signals recorded from 12 rats
      before and after contusion spinal cord injury at thoracic vertebra T8. The
      statistical analysis results revealed significant effect of injury to hindlimbs,
      whereas almost none to forelimbs. Thus, the results show high potential of this
      technique to differentiate between normal and injured spinal cord.

PMID- 19163763
TI  - Probabilistic assessment of Autonomic Nervous System fluctuations during tilt
      table tests.
AB  - A number of reports have advocated the use of Heart Rate Variability (HRV) as a
      non invasive method of monitoring the Autonomic Nervous System (ANS). In the
      anesthesia and critical care monitoring settings, the development of an
      instrument able to provide real-time information about the ANS state at different
      stages of any procedure would provide improved safety for patients undergoing
      diagnostic or therapeutic interventions. However, real-time analysis of HRV can
      be particularly challenging since larger effective lengths of observation provide
      better spectral resolution. Our study explores a probabilistic approach that
      analyzes changes in HRV parameters obtained from an autoregressive (AR) model
      technique using Burg's methods to evaluate very short observation windows while
      preserving appropriate frequency resolution. These HRV parameters are continuosly
      compared to a baseline state, and a probability trend is updated during
      provocative maneuvers. Preliminary results show that trends from classical
      parameters such as RMSSD and LFn are consistent and reliable instruments capable
      of providing significant information about ANS fluctuations in a timely fashion.

PMID- 19163764
TI  - Heart rate variability and complexity in people with diabetes associated cardiac
      autonomic neuropathy.
AB  - Cardiac autonomic neuropathy (CAN) in diabetes has been called a 'silent killer',
      because so few patients realize that they suffer from it, and yet its effect can
      be lethal. Early sub clinical detection of CAN and intervention are of prime
      importance for risk stratification in preventing sudden death due to silent
      myocardial infarction. This study presents the usefulness of heart rate
      variability (HRV) and complexity analyses from short term ECG recordings as a
      screening tool for CAN. Poincare plot indexes and sample entropy (SampEn) measure
      of HRV were used for analyzing variability (short and long term) and complexity
      respectively. Analyses were performed on the different length of HRV records
      during supine rest. Reduced Poincare plot patterns and higher SampEn were found
      in CAN+ group. Significant changes in HRV parameters of CAN+ group during the
      course of supine rest were found in contrast to control group (CAN-). Our results
      demonstrated the potential utility of nonlinear HRV parameters in identifying
      asymptomatic CAN.

PMID- 19163765
TI  - Assessment of the effects of subthalamic stimulation in Parkinson disease
      patients by artificial neural network.
AB  - This study aims at applying an artificial neural network for the evaluation of
      the effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on
      Parkinson disease (PD) patients with and without medication. A sample of 15 PD
      patients who have undergone STN DBS were evaluated under four test conditions:
      medication off and stimulation off (mof-sof), medication off and stimulation on
      (mof-son), medication on and stimulation off (mon-sof) and medication on and
      stimulation on (mon-son). A control group with 30 subjects was also evaluated.
      Principal component analysis (PCA) was applied on vertical ground reaction force
      (vGRF) and the first six principal component scores (PC score) were obtained in
      both groups. Those PCs scores were used as input in a probabilistic neural
      network (PNN). PNN presented satisfactory classification performance in the
      separation of controls and PD with 90.1% accuracy, 69.2% sensitivity and 100%
      specificity. The stimulation mof-son and mon-son conditions presented better
      results compared to mon-sof. In the mof-son condition, 41.7% were classified as
      normal, while further enhancement (63.3%) was given by the mon-son condition.
      These results indicated the potentiality of PNN to quantitatively evaluate
      treatment effects. Furthermore, STN DBS shows improvement on vGRF pattern in PD
      patients, most substantially when used with medication.

PMID- 19163766
TI  - On correlating otoacoustic emissions with blood glucose levels.
AB  - The long term objective of this research is to develop a new means for diabetic
      patients to painlessly and non-invasively monitor their blood glucose levels. We
      propose a novel method for noninvasive glucose monitoring based on measurement
      and analysis of otoacoustic emissions (OAEs). OAEs are low-intensity sounds
      generated by the cochlea in response to acoustic stimuli. Evoking and measuring
      OAEs is done using a tiny speaker and microphone that fit snugly inside the ear
      canal. The OAE response can be partially masked or reduced in amplitude by
      presenting competing acoustic stimuli contralaterally (opposite ear),
      ipsilaterally (same ear), or both. This masking effect is caused by activation of
      neural efferent pathways from the brain. Neural effects, including evoked
      responses such as auditory brainstem responses and axonal transmission latencies,
      are known to correlate with glucose. This suggests that masked OAEs may correlate
      with glucose since masking is a result of neural activity, and neural activity is
      affected by glucose levels. Prior to our research, no studies have investigated
      the correlation of masked OAEs with blood glucose. In this paper we present our
      preliminary findings, including experimental results that suggest a correlation
      with blood glucose levels.

PMID- 19163767
TI  - A multivariate density estimator for contrast agent injection monitoring using a
      Bayesian sparse kernel approach.
AB  - The administration of intravenous contrast media during CT examinations is
      routine, but carries with it a risk of extravasation. Hence, we define an
      injection state to be either intravenous or extravasated. With a new Doppler
      ultrasound monitoring technique, we propose a method for estimating the
      probability of an injection state during the various stages of an examination. A
      smoothed time-frequency representation of the Doppler signal is used to analyze
      at which frequencies there is the largest difference in response between signals
      from intravenous and extravasated injections. A vector of response values based
      on this analysis forms this study's feature space. A Relevance Vector Machine is
      used to estimate the probability density for a particular injection state. We
      present preliminary results (n=5) showing the time-frequency representation of
      the Doppler ultrasound signal, the frequency analysis and the density estimation.

PMID- 19163768
TI  - Cerebral hypoxic ischemia at different cerebral oxygen saturations in piglets:
      amplitude-integrated EEG study.
AB  - OBJECTIVE: the objective of present paper was to study the amplitude-integrated
      EEG (aEEG) in hypoxic ischemic (HI) animal models and to test the reliability of
      aEEG method when used to monitor cerebral injuries. METHOD: HI animal models were
      constructed and classified into mild, moderate and severe cerebral oxygen
      saturation groups according to regional oxygen saturation (rSO(2)) in brains.
      Then aEEG waveforms were obtained from raw EEG data using digital signal
      processing. RESULT: aEEG reflected cerebral functions consistently and accurately
      at different cerebral rSO(2) levels. aEEG waveforms rarely changed in the group
      of mild HI; they dropped but recovered in moderate HI group; and aEEG maintained
      very low after HI in the cases when severe HI happened. CONCLUSION: aEEG method
      could monitor cerebral functions directly, accurately and consistently. It is a
      reliable tool to continuously evaluate cerebral injuries.

PMID- 19163769
TI  - Imaging coherent sources of tremor related EEG activity in patients with
      Parkinson's disease.
AB  - The cortical sources of both the basic and first 'harmonic' frequency of
      Parkinsonian tremor are addressed in this paper. The power and coherence was
      estimated using the multitaper method for EEG and EMG data from 6 Parkinsonian
      patients with a classical rest tremor. The Dynamic Imaging of Coherent Sources
      (DICS) was used to find the coherent sources in the brain. Before hand this
      method was validated for the application to the EEG by showing in 3 normal
      subjects that rhythmic stimuli (1-5Hz) to the median nerve leads to almost
      identical coherent sources for the basic and first harmonic frequency in the
      contralateral sensorimotor cortex which is the biologically plausible result. In
      all the Parkinson patients the corticomuscular coherence was also present in the
      basic and the first harmonic frequency of the tremor. However, the source for the
      basic frequency was close to the frontal midline and the first harmonic frequency
      was in the region of premotor and sensory motor cortex on the contralateral side
      for all the patients. Thus the generation of these two oscillations involves
      different cortical areas and possibly follows different pathways to the
      periphery.

PMID- 19163770
TI  - New wearable system for the step counting based on the codivilla-spring for daily
      activity monitoring in stroke rehabilitation.
AB  - Remote therapy, involved in a tele-rehabilitation program, should monitor daily
      motion activity. Furthermore, patients should have all possible means to improve
      rehabilitation care at their disposal, such as suitable prostheses and
      biofeedback tools. During stroke rehabilitation at home, the most used equipment
      is the AFO prosthesis, which is also called codivilla-spring, as it is used in
      cases of both bilateral and mono-lateral damage. A new codivilla-spring
      prosthesis with sensors for telemonitoring / telerehabilitation has been designed
      and constructed. It provides step counting. It is based on a couple of force
      sensing resistors affixed in the plantar area of the prosthesis, and a wearable
      unit with a micro-processor microP PIC 16F877 (Microchip, USA). The data exchange
      is assured by the Aurel-XTR-434H telemetric system. While ambulating, FSRs detect
      the pressure of the foot-tip and heel. The PIC on the basis of an algorithm
      furnishes the step-counting. The proposed sensorized-codivilla-spring (SECOSP)
      was tested as a step-counter on three subjects after stroke-rehabilitation with
      mono-lateral damage at Level 2 of the Tinetti test of unbalance. These subjects
      performed 100 steps with two different instructions (fast, slow). The mean error
      was lower than 0.6 %. The next phase will be the optimization of SECOSP for long
      term medical application in a patient's home.

PMID- 19163771
TI  - Entropy analysis on EEG signal in a case study of focal myoclonus.
AB  - Electrophysiological studies provide useful information for diagnosis and
      classification of myoclonus, and for the investigation of its generative
      mechanisms, due to association of myoclonus with abnormally increased
      excitability of cortical structures. In this work we analyzed the polygraphic
      data of a 7-year old girl affected by continuous partial epilepsy with focal
      myoclonus both related and not related with epileptiform discharges on EEG. We
      applied Sample Entropy (SampEn) and Lempel-Ziv complexity (LZ) methods to
      investigate the regularity and complexity content of EEG recordings and to find
      possible analogies in the behaviour of non-parametric complexity measures in
      epilepsy and in myoclonus. Our results show that these algorithms succeeded in
      finding a significant difference between the hypothesized focus on C3 electrode
      and the contralateral electrode C4, for EEG correlated myoclonus. A significant
      difference between the two contralateral electrodes (C3-C4) was also found for
      non EEG correlated myoclonus, but only by means of SampEn. This preliminary study
      confirmed the ability of entropic methods in discriminating myoclonic events.
      Indeed, near the myoclonic focus location both SampEn and LZ methods showed below
      average values.

PMID- 19163772
TI  - Fetal distress diagnosis using heart rate variability analysis: design of a high
      frequency variability index.
AB  - Routine monitoring of Fetal Heart Rate (FHR) during labor enables diagnosis of
      fetal distress and appropriate management by the medical staff. Diagnosis of
      fetal distress relies mainly on a subjective visual assessment of FHR variations
      using baseline level, oscillations magnitude, decelerations and their time
      relation to the parturient uterine contractions. Strong intra and inter-observer
      discrepancies exist with this widely used technique, and sometimes requires fetal
      scalp blood sample pH measurement, which is not fully reliable either. Gold
      standard assessment of fetal distress relies on blood pH measurement after the
      birth. In this paper we describe a new method for fetal distress diagnosis based
      on FHR variability analysis, measuring the high frequency content of FHR as a
      High Frequency Variability Index (HFVI). We tested this new index on 21 fetuses
      where FHR was recorded during labor for an observational clinical trial. FHR
      recordings were separated in two groups given the fetal arterial pH obtained
      after birth: group 1 - no distress, pH >= 7.15, N=16 and group 2 - fetal
      distress, pH 7.15, N=5. The new index was significantly higher in group 1 than in
      group 2 (non parametric Mann Whitney U-test, p=0.01).

PMID- 19163773
TI  - A novel VOCODER for cochlear implants.
AB  - A new VOCODER-based speech processing strategy for cochlear implants is
      presented. The proposed method improves upon existing VOCODER techniques in time
      frequency resolution and can offer higher noise immunity. The presented method is
      based on the effective tracking of nonstationary sinusoid components using a non
      linear sinusoid tracking algorithm (STA). The structure of the proposed
      technique, as well as the underlying STA are presented. It is expected that the
      improvement in time-frequency resolution will offer superior performance in
      cochlear implants, as well as improvements in speech coding applications. An
      eight-band version of the proposed technique is presented and superior
      performance to existing techniques is shown.

PMID- 19163774
TI  - A real-time ECG data compression algorithm for a digital holter system.
AB  - This paper describes a real time ECG compression algorithm for a digital holter
      system. Proposed algorithm consists of five main procedures. First procedure is
      to differentiate signals, second is to choose a period of the differentiated
      signals and store them in memory, third is to perform the DCT(Discrete Cosine
      Transform) on the stored data, fourth is to apply a window filter, and fifth
      procedure is to apply Huffman Coding compression method on the data. This
      developed algorithm has been tested by applying 12 ECGs(electrocardiograms) from
      the MIT-BIH database and the PRD(Percent RMS Difference) and the CR(Compression
      Ratio) are calculated. It is found that the algorithm achieved a high level of
      compression performance with 1.82 of PRD and 8.82:1 of CR in average.

PMID- 19163775
TI  - Error analysis on spinal motion measurement using skin mounted sensors.
AB  - Measurement errors of skin-mounted sensors in measuring forward bending movement
      of the lumbar spines are investigated. In this investigation, radiographic images
      capturing the entire lumbar spines' positions were acquired and used as a 'gold'
      standard. Seventeen young male volunteers (21 (SD 1) years old) agreed to
      participate in the study. Light-weight miniature sensors of the electromagnetic
      tracking systems-Fastrak were attached to the skin overlying the spinous
      processes of the lumbar spine. With the sensors attached, the subjects were
      requested to take lateral radiographs in two postures: neutral upright and full
      flexion. The ranges of motions of lumbar spine were calculated from two sets of
      digitized data: the bony markers of vertebral bodies and the sensors and
      compared. The differences between the two sets of results were then analyzed. The
      relative movement between sensor and vertebrae was decomposed into sensor sliding
      and titling, from which sliding error and titling error were introduced. Gross
      motion range of forward bending of lumbar spine measured from bony markers of
      vertebrae is 67.8 degrees (SD 10.6 degrees ) and that from sensors is 62.8
      degrees (SD 12.8 degrees ). The error and absolute error for gross motion range
      were 5.0 degrees (SD 7.2 degrees ) and 7.7 degrees (SD 3.9 degrees ). The
      contributions of sensors placed on S1 and L1 to the absolute error were 3.9
      degrees (SD 2.9 degrees ) and 4.4 degrees (SD 2.8 degrees ), respectively.

PMID- 19163776
TI  - Estimation of vital signs in bed from a single unobtrusive mechanical sensor:
      algorithms and real-life evaluation.
AB  - A single contact-less mechanical sensor is exploited for estimating three vital
      signs during sleep, namely, the heart rate, the breathing rate and an activity
      index related to the body movements. Robust estimations are achieved over epochs
      of 30 seconds. The data processing is performed with standard DSP techniques
      leading to an integrated solution for dealing with body motion artifacts. The
      algorithms are described and evaluated over a one-hundred night corpus collected
      from real-life recordings of healthy subjects and sleep-laboratory patients.
      Results show that the average error of the heart rate is of 1.25 beat per minute
      compared to the reference values from an ECG and the coverage of the mechanically
      derived estimates is 83%.

PMID- 19163777
TI  - Surface EMG and spatial resolution analysis with estimation of electromyographic
      descriptors.
AB  - Spatial filtering has become a common way to improve the resolution of surface
      electromyographic signals (SEMG) when used in connection with electrode arrays.
      The goal of this study is to observe the behavior of S-EMG amplitude and spectral
      descriptors when signals are submitted to a longitudinal quadruple
      differentiating spatial filter. Signals were acquired at 20% and 60% of the
      maximum voluntary contraction using a linear array of eight surface electrodes in
      order to understand the impact of the filtering technique in the S-EMG variables
      during fatiguing and non-fatiguing contractions. The final results show that the
      filtering procedure yields better selectivity, suggesting that single motor units
      can be better observed if spatial filters and measurement configurations with
      smaller pick-up areas are used. During fatiguing contractions, however, further
      analysis is needed.

PMID- 19163778
TI  - Surface electromyogram signal estimation based on wavelet thresholding technique.
AB  - Surface Electromyogram signal collected from the surface of skin is a
      biopotential signal that may be influenced by different types of noise. This is a
      considerable drawback in the processing of the sEMG signals. To acquire the clean
      sEMG that contains useful information, we need to detect and eliminate these
      unwanted parts of signal. In this work, a new method based on wavelet
      thresholding technique is presented which provides an acceptable purified sEMG
      signal. sEMG signals for this study are extracted for various hand movements. We
      use three hand movements to calculate the near optimal estimation parameters. In
      this work two types of thresholding techniques, namely Stein unbiased risk (SURE)
      estimator and adaptive Bayes estimator are utilized coupled with selected types
      of mother wavelets with different levels of decomposition. After designing the
      estimation technique, for evaluating the efficacy of method, the formed signals
      are sent to a pattern recognition system in order to discriminate among eight
      hand movements. The acquired results indicate that the wavelet based estimation
      technique using SURE thresholding approach is an appropriate method for producing
      sEMG signals without noise that may result in considerable improvement in the
      application of hand movement recognition.

PMID- 19163779
TI  - Combining newborn EEG and HRV information for automatic seizure detection.
AB  - We propose a new seizure detection framework based on combination of information
      extracted from newborn multi-channel electroencephalogram (EEG) and heart rate
      variability (HRV). Two approaches are investigated for the combination of EEG and
      HRV, namely; feature fusion and classifier/decision fusion. The feature fusion
      was performed by concatenating the features vectors extracted from the EEG and
      the HRV signals while the classifier fusion was accomplished by fusing the
      independent decisions from individual classifiers of EEG and HRV. Both proposed
      schemes consist of a sequence of processing steps, namely; preprocessing, feature
      extraction, feature selection and finally the combination. We have shown that
      both proposed approaches lead to improved performance of newborn seizure
      detection compared to either EEG or HRV based seizure detectors.

PMID- 19163780
TI  - Performance evaluation of three methods for respiratory signal estimation from
      the electrocardiogram.
AB  - A comparative study of three methods for estimating respiratory signal through
      electrocardiogram (ECG) was carried out. The three methods analyzed were based on
      R wave area, R peak amplitude and heart rate variability (HRV). For each method,
      cross-correlation coefficient and spectral coherence in a range of frequencies up
      to 0.5 Hz were computed between the ECG derived respiratory signals (EDR) and the
      three real respiratory signals: oronasal, and two inductance plethysmographies
      recordings (chest and abdominal). Results indicate that EDR methods based on R
      wave area and HRV are better correlated and show a wider spectral coherence with
      real respiratory signals than the other EDR method based on R peak amplitude.

PMID- 19163781
TI  - Detection of low amplitude fetal QRS complexes.
AB  - The significance of the most important operations performed by the noninvasive
      systems for fetal heart rate determination is investigated. The method of
      template subtraction for maternal ECG suppression is compared to the method based
      on independent component analysis. The QRS detector based on the classical slope
      responsive preprocessing competes with the one that employs normalized matched
      filtering for QRS enhancement. A small database containing the four-channel
      abdominal ECG signals with the marked positions of the fetal QRS complexes is
      prepared to enable the investigations. The performed experiments show the factors
      that have the greatest impact on the results of the fetal QRS detection, and an
      effective approach to cope the problem is proposed.

PMID- 19163782
TI  - Computer aided diagnosis of fatty liver ultrasonic images based on support vector
      machine.
AB  - B-scan ultrasound is the primary means for the diagnosis of fatty liver. However,
      due to use of various ultrasound equipments, poor quality of ultrasonic images
      and physical differences of patients, fatty liver diagnosis is mainly
      qualitative, and often depends on the subjective judgment of technicians and
      doctors. Therefore, computer-aided feature extraction and quantitative analysis
      of liver B-scan ultrasonic images will help to improve clinical diagnostic
      accuracy, repeatability and efficiency, and could provide a measure for severity
      of hepatic steatosis. This paper proposed a novel method of fatty liver diagnosis
      based on liver B-mode ultrasonic images using support vector machine (SVM). Fatty
      liver diagnosis was transformed into a pattern recognition problem of liver
      ultrasound image features. According to the different characteristics of fatty
      liver and healthy liver, important image features were extracted and selected to
      distinguish between the two categories. These features could be represented by
      near-field light-spot density, near-far-field grayscale ratio, grayscale co
      occurrence matrix, and neighborhood gray-tone difference matrix (NGTDM). A SVM
      classifier was modeled and trained using the clinical ultrasound images of both
      fatty liver and normal liver. It was then exploited to classify normal and fatty
      livers, achieving a high recognition rate. The diagnostic results are
      satisfactorily consistent with those made by doctors. This method could be used
      for computer-aided diagnosis of fatty liver, and help doctors identify the fatty
      liver ultrasonic images rapidly, objectively and accurately.

PMID- 19163783
TI  - Automated detection of Polycystic Ovary Syndrome from ultrasound images.
AB  - Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder which seriously
      impacts women's health. The disorder is characterized by the formation of many
      follicular cysts in the ovary. Nowadays the diagnosis performed by doctors is to
      manually count the number of follicular cysts, which may lead to problems of the
      variability, reproducibility and low efficiency. To overcome these problems, an
      automated scheme is proposed to detect the PCOS. Firstly the input ovary
      ultrasound image is filtered by an adaptive morphological filter. Then a modified
      labeled watershed algorithm is used to extract contours of targets. Finally a
      clustering method is applied to identify expected follicular cysts. The
      experimental application verifies the effectivity of this proposed scheme, which
      achieves the accuracy rate of 84%.

PMID- 19163784
TI  - Study of a mammographic CAD performance dependence on the considered mammogram
      set.
AB  - This work analyzes the influence of the set of mammograms used in the training
      processes of a computer aided diagnosis system on the overall performance. We
      used the mammograms provided by the Digital Database for Screening Mammography,
      one of the most extended research database. The obtained results seem to suggest
      an effect on the performance values obtained in a CAD system with different
      database subsets. Therefore, in order to make valid comparisons between CAD
      systems, the specification of the mammogram set used to test the system is of the
      utmost importance.

PMID- 19163785
TI  - Bleeding detection from capsule endoscopy videos.
AB  - Reviewing medical videos for the presence of disease signs presents a unique
      problem to the conventional image classification tasks. The learning process
      based on imbalanced data set is heavily biased and tends to result in low
      sensitivity. In this article, we present a classification method for finding
      video frames that contain bleeding lesions. Our method re-balances the training
      samples by over-sampling the minority class and under-sampling the majority
      class. An SVM ensemble is then constructed using re-balanced data of three kinds
      of image features. Five sets of image frames were used in our experiments, each
      of which contains approximately 55,000 images and the ratio of minority and
      majority class is about 1:145. Our preliminary results demonstrated superior
      performance in sensitivity and comparative subjectivity with slight improvement.

PMID- 19163786
TI  - Cardiac disease recognition in echocardiograms using spatio-temporal statistical
      models.
AB  - In this paper we present a method of automatic disease recognition by using
      statistical spatio-temporal disease models in cardiac echo videos. Starting from
      echo videos of known viewpoints as training data, we form a statistical model of
      shape and motion information within a cardiac cycle for each disease.
      Specifically, an active shape model (ASM) is used to model shape and texture
      information in an echo frame. The motion information derived by tracking ASMs
      through a heart cycle is then represented compactly using eigen-motion features
      to constitute a joint spatio-temporal statistical model per disease class and
      observation viewpoint. Each of these models is then fit to a new cardiac echo
      video of an unknown disease, and the best fitting model is used to label the
      disease class. Results are presented that show the method can discriminate
      patients with hypokinesia from normal patients.

PMID- 19163787
TI  - Automatic detection of clustered microcalcifications in digital mammograms: Study
      on applying adaboost with SVM-based component classifiers.
AB  - This paper presents a computer-aided diagnosis (CAD) system for automatic
      detection of clustered microcalcifications (MCs) in digitized mammograms. The
      proposed system consists of two main steps. First, potential MC pixels in the
      mammograms are segmented out by using four mixed features consisting of two
      wavelet features and two gray level statistical features and then the potential
      MC pixels are labeled into potential individual MC objects by their spatial
      connectivity. Second, MCs are detected by extracting a set of 17 features from
      the potential individual MC objects. The classifier which is used in the first
      step is a multilayer feedforward neural network classifier but for the second
      step we have used Adaboost with SVM-based component classifier. Component
      classifiers which we used in our combining method are SVM classifiers with RBF
      kernel. The method was applied to a database of 40 mammograms (Nijmegen database)
      containing 105 clusters of MCs. A free-response operating characteristics (FROC)
      curve is used to evaluate the performance of CAD system. Results show that the
      proposed system gives quite satisfactory performance. In particular, 89.55% mean
      true positive detection rate is achieved at the cost of 0.921 false positive per
      image.

PMID- 19163788
TI  - Respiratory acoustic thoracic imaging (RATHI): assessing intrasubject
      variability.
AB  - Respiratory acoustic thoracic imaging (RATHI) permits analysing lung sounds (LS)
      temporal and spatial distribution, however, a deep understanding of RATHI
      repeatability associated with the pulmonary function is necessary. As a
      consequence, in the current work intrasubject variability of RATHI is evaluated
      at different airflows. For generating RATHIs, LS were acquired at the posterior
      thoracic surface. The associated image was computed at the inspiratory phases by
      interpolation through a Hermite function. The acoustic information of eleven
      subjects was considered at airflows of 1.0, 1.5 and 2.0 L/s. Several RATHIs were
      generated for each subject according to the number of acquired inspiratory
      phases. Quadratic mutual information based on Cauchy-Schwartz inequality (I(CS))
      was used to evaluate the degree of similitude between intrasubject RATHIs. The
      results indicated that, for the same subject, I(CS) averaged 0.893, 0.897, and
      0.902, for airflows of 1.0, 1.5, and 2 L/s, respectively. In addition, when the
      airflow was increased, increments in intensity values and in the dispersion of
      the spatial distribution reflected in RATHI were observed. In conclusion, since
      the intrasubject variability of RATHI was low for airflows between 1.0 and 2.0
      L/s, the pattern of sound distribution during airflow variations is repeatable
      but differences in sound intensity should be considered.

PMID- 19163789
TI  - Asymmetry in lung sound intensities detected by respiratory acoustic thoracic
      imaging (RATHI) and clinical pulmonary auscultation.
AB  - RATHI was introduced as an attempt to further improve the association between
      anatomical zones and specific breathing activity, both spatially and temporally.
      This work compares RATHI with clinical pulmonary auscultation (PA) to assess the
      concordance between both procedures to detect asymmetries in lung sound (LS)
      intensities. Twelve healthy young males participated in the study and were
      auscultated by two experts. RATHI consisted in the acquisition of acoustical
      signals with an array of 5x5 sensors, while experts auscultated and described the
      intensity of LS heard using the same stethoscope on each sensor's position within
      the array. Comparisons were established looking for intensity asymmetries between
      apical vs. basal pulmonary regions and right vs. left hemithorax. By RATHI, most
      of the subjects showed asymmetries between apical and basal regions higher than
      20%, whereas between left and right hemithorax asymmetries higher than 20%
      occurred only half of the time. RATHI and PA agreed 83 to 100% when apical to
      base acoustical information was compared, but when left to right asymmetries were
      considered these figures were about 40 to 50%. We concluded that RATHI has
      advantages as it gave more detailed and measurable information on LS than
      clinicians, who could not detect intensity asymmetries mainly below 20%.

PMID- 19163790
TI  - Imaging of simulated crackle sounds distribution on the chest.
AB  - Crackles sounds have been associated with several pulmonary pathologies and
      diverse algorithms have been proposed for extracting and counting them from the
      acquired lung sound. These tasks depend among other factors, of the relation
      between the magnitude of the crackle and the background lung sound. In this work,
      we explore multivariate signal processing to deal with the tasks and propose a
      new concept, the discontinuous adventitious sounds imaging. The image formation
      is founded on the results of two proposed methodologies that use an
      autoregressive (AR) model. In the first case, the AR coefficients feed an
      artificial neural network (ANN) to classify temporal acoustic information as
      healthy or sick and; in the second case, a time-variant AR (TVAR) model, obtained
      by the RLS algorithm, permits to detect changes in the TVAR coefficients to be
      associated with the number of crackles. For AR-ANN, the ratio of the temporal
      windows classified as sick to the classified as healthy is used as an index to
      form the adventitious image, while for TVAR-RLS, an estimation of the number of
      crackles is obtained to form the corresponding image. The results indicated that
      fine and coarse crackles could be detected and counted even with very low crackle
      magnitude so that the formation of a crackle distribution image was consistent.

PMID- 19163791
TI  - Objective grading of facial paralysis using Local Binary Patterns in video
      processing.
AB  - This paper presents a novel framework for objective measurement of facial
      paralysis in biomedial videos. The motion information in the horizontal and
      vertical directions and the appearance features on the apex frames are extracted
      based on the Local Binary Patterns (LBP) on the temporal-spatial domain in each
      facial region. These features are temporally and spatially enhanced by the
      application of block schemes. A multi-resolution extension of uniform LBP is
      proposed to efficiently combine the micro-patterns and large-scale patterns into
      a feature vector, which increases the algorithmic robustness and reduces noise
      effects while still retaining computational simplicity. The symmetry of facial
      movements is measured by the Resistor-Average Distance (RAD) between LBP features
      extracted from the two sides of the face. Support Vector Machine (SVM) is applied
      to provide quantitative evaluation of facial paralysis based on the House
      Brackmann (H-B) Scale. The proposed method is validated by experiments with 197
      subject videos, which demonstrates its accuracy and efficiency.

PMID- 19163792
TI  - Refined segmentation of images for human pose analysis.
AB  - Image-based gait analysis as a means of biometric identification has attracted
      much research attention. Most of the existing methods focus on human posture
      identification and tracking. There have been few investigations on the
      relationship between the carried load by a person and the change of gait
      characteristics. Nevertheless, this relationship can be very useful in a number
      of applications, such as studying the postural effects of load on children and
      adolescence. In this paper, we investigate how to estimate carried weight from a
      sequence of images of a person walking normally. Observing that human tends to
      minimize energy expenditure during walking, we compute several angles of body
      leaning and determine the relationship among the carried weight, the leaning
      angles, and the location of the center of gravity. This method has been verified
      successfully by experiments.

PMID- 19163793
TI  - Genetic algorithm-based PCA eigenvector selection and weighting for automated
      identification of dementia using FDG-PET imaging.
AB  - Parametric FDG-PET data offer the potential for an automated identification of
      the different dementia syndromes. Principal component analysis (PCA) can be used
      for feature extraction in FDG-PET. However, standard PCA is not always successful
      in delineating the features that have the best discrimination ability. We report
      a genetic algorithm-based method to identify an optimal combination of
      eigenvectors so that the resultant features are capable of successfully
      separating patients with suspected Alzheimer's disease and frontotemporal
      dementia from normal controls. We compared our approach with standard PCA on a
      set of 210 clinical cases and improved the performance in separating the dementia
      types with an accuracy of 90.0% and a Kappa statistic of 0.849. There was very
      good agreement between the automated technique and the diagnosis given by
      clinicians.

PMID- 19163794
TI  - Local electrical stimulation of cultured embryonic cardiomyocytes with sub
      micrometer nail structures.
AB  - In this paper, we demonstrate the feasibility of selective extracellular
      electrical stimulation at the (sub)cellular level in dissociated cultured cells.
      Using a CMOS-compatible process, we have fabricated an electrode array with sub
      micrometer nail probes. Due to their particular configuration, the nails are
      strongly engulfed by the cellular membrane. By measuring the calcium signals, we
      found that electrical stimulation via the micronails activates the cell locally,
      in a dose-dependent manner, with very low applied currents. The results suggest
      the applicability of the device in pharmacological or signal propagation studies.

PMID- 19163795
TI  - A Research for evaluation on stress change via thermotherapy and massage.
AB  - In this research, a device, which has a thermotherapic and massaging function and
      relaxes muscles, was used to evaluate the effect muscle relaxation has on stress
      relief. Therefore, the physiological changes namely Heart Rate (HR), Heart Rate
      Variability (HRV) and Skin Temperature (SKT) of the subjects which reflect the
      autonomic nervous system and cardiovascular relationship were obtained and
      analyzed. In order to evaluate the assumption that the treatment relieves the
      subject's physiological and psychological stress, experiment was carried out on
      25 adults (13 male and 12 female, age 52.32+/-18.121) through stages consisted of
      relaxation, pre-treatment, treatment and post-treatment. Treatment was provided
      to the back, stomach and leg area by massaging 55 degrees C heat to the back.
      According as the physiological changes of subjects before and after treatment
      were compared, the present research was able to prove that thermotherapy and
      massage treatment induces physiological change of patients thus relieves stress.

PMID- 19163796
TI  - Blood cell counting by means of impedance measurements in a microsystem device.
AB  - This paper presents an innovative, portable and low power blood cell counter,
      based on micro-electro-mechanical-systems (MEMS) technology. It was realized by
      designing and developing a custom impedance measurement circuit, which drives an
      electro-fluidic microsystem, providing a parallel, multi-channel Coulter counter.
      A method for a reliable, easy, and low-cost interfacing to such kind of micro
      devices, allowing both fluidic and electric coupling, is also shown. Preliminary
      experiments led to promising results: fluidics works properly without leakages or
      clogging. Electrodes show good stability with current (in terms of adhesion), and
      measured channel impedances are satisfyingly low (30 kW for a cubic Coulter
      orifice, side 10 microm). Finally, we present a possible extension of the setup,
      based on a dual-characteristic, electro-optical counting.

PMID- 19163797
TI  - A fast and accurate FPGA based QRS detection system.
AB  - An accurate Field Programmable Gate Array (FPGA) based ECG Analysis system is
      described in this paper. The design, based on a popular software based QRS
      detection algorithm, calculates the threshold value for the next peak detection
      cycle, from the median of eight previously detected peaks. The hardware design
      has accuracy in excess of 96% in detecting the beats correctly when tested with a
      subset of five 30 minute data records obtained from the MIT-BIH Arrhythmia
      database. The design, implemented using a proprietary design tool (System
      Generator), is an extension of our previous work and uses 76% resources available
      in a small-sized FPGA device (Xilinx Spartan xc3s500), has a higher detection
      accuracy as compared to our previous design and takes almost half the analysis
      time in comparison to software based approach.

PMID- 19163798
TI  - System for ECG and heart rate monitoring during group training.
AB  - We present a system for measuring ECG signals simultaneously from multiple
      persons during a group training session. The system transmits the signals to a
      coordinating computer where heart rate and other parameters are calculated from
      the signals. The heart rate values can then be shown for example through a video
      projector on a large display along with individual information about the training
      intensity.

PMID- 19163799
TI  - Monitoring 3D movements for the rehabilitation of joints in physiotherapy.
AB  - This article tackles several problems faced by professionals in physiotherapy:
      the performance of the rehabilitation exercises by the patients, the control of
      the course of the illness and the patient's ignorance about whether or not he is
      properly performing the exercises. We propose a solution based on the use of the
      Wii Controller to control the exercise movements, along with software that
      provides the patient with an easy, intuitive and interactive control system.
      Finally, web services are used to allow the remote monitoring of the treatment by
      physiotherapy professionals.

PMID- 19163801
TI  - Lingual force detection system.
AB  - The tongue is an organ of great significance in the processes of both swallowing
      and speech. Any disorder of the tongue's function (dysphagia, lateral sclerosis),
      with regard especially to the forces it produces, can drastically impair an
      individual by leaving them unable to swallow or talk. Up to this point, few
      systems have been created to quantitatively measure tongue force. Here we
      describe development of a new device that measures and outputs tongue force and
      endurance at six strategically positioned points in the mouth. Two mouth guards
      were fitted with six (three per guard) thin, highly sensitive sensors that
      independently output tongue force at each location. To ensure proper sensor
      readings, that is, reliable contact between the tongue and the sensor, each
      sensor was placed between a hard backing plate of stainless steel and a pliable
      puck constructed from silicone rubber. Forces were output to a computer using
      National Instruments' ELVIS system and a novel user friendly interface created
      using NI's LabVIEW. The proposed system can be utilized as a first step in
      diagnosis and treatment planning for speech rehabilitation and therapy. In future
      studies, collected data will be compared with control data (obtained previously
      from healthy volunteers) to diagnose potential tongue weakness and pinpoint its
      location in the mouth (whether unilateral or diffuse).

PMID- 19163800
TI  - Software platform for rapid prototyping of NIRS brain computer interfacing
      techniques.
AB  - This paper describes the control system of a next-generation optical brain
      computer interface (BCI). Using functional near-infrared spectroscopy (fNIRS) as
      a BCI modality is a relatively new concept, and research has only begun to
      explore approaches for its implementation. It is necessary to have a system by
      which it is possible to investigate the signal processing and classification
      techniques available in the BCI community. Most importantly, these techniques
      must be easily testable in real-time applications. The system we describe was
      built using LABVIEW, a graphical programming language designed for interaction
      with National Instruments hardware. This platform allows complete configurability
      from hardware control and regulation, testing and filtering in a graphical
      interface environment.

PMID- 19163802
TI  - Hydrogel-based microfluidic systems for co-culture of cells.
AB  - Currently, in vivo cellular microenvironments are not well modeled using
      traditional cell culture methods. Microfluidic technology provides the tools to
      mimic in vivo environments for cell culture. We use alginate hydrogels to
      reversibly trap and release cells for incubation. The porous nature of alginate
      gels resembles the natural extracellular matrix and allows the transport of
      nutrients and waste. This property makes it an ideal cell trapping and culturing
      material. Here, we present reversible immobilization of human fetal lung
      fibroblasts (HFL1) and human hepatocellular liver carcinoma cell (Hep G2) inside
      microfluidic channels and demonstrate the possibility of co-culturing these two
      cell types within different alginate gel layers.

PMID- 19163803
TI  - Electrocardiographic pill for cattle heart rate determination.
AB  - Decreased agricultural profit margins and recent bioterrorism concerns have led
      to an increased interest in monitoring livestock health. Heart rate and core body
      temperature are traditional vital parameters for cattle health assessment, as
      they provide warnings for illness and disease. However, obtaining these data in
      the field is time and labor intensive, which speaks to the need for solutions
      that provide continuous and automatic acquisition of these parameters. This paper
      presents the design of a pill that can remain in an animal's reticulum and use
      electrocardiographic techniques to ascertain heart rate. The wired prototype has
      been tested with a fistulated steer. These tests demonstrate that consistent
      heart vector data can be acquired even in the presence of animal movement and
      rumination. After minor processing, these signals are suitable for use with peak
      detection circuitry that can automate heart rate determination.

PMID- 19163804
TI  - Cerebral temperature varies across circadian phases in humans.
AB  - The 24-hour rhythm of core body temperature (CBT) is commonly used in humans as a
      tool to assess the oscillation of the central endogenous circadian pacemaker. The
      invasive nature of the rectal sensor used to collect CBT makes it difficult to
      use in ambulatory conditions. Here we validate the use of a newly developed brain
      temperature (BT) sensor against that of a standard rectal temperature sensor
      using a 72-hour ultra-rapid sleep-wake (URSW) cycle procedure. A significant
      circadian variation of both body temperature recordings was observed from which a
      phase and amplitude was reliably determined. These results indicate that BT can
      be refined as a non-invasive alternative to CBT measurements in the evaluation of
      circadian phase in field conditions.

PMID- 19163805
TI  - Bandwidth measurement of the conductance catheter system.
AB  - Conductance catheter system is used to estimate real-time ventricular volume by
      measuring the time-varying ventricular conductance/admittance. However, the
      system is generally calibrated only with known resistors, while neither the
      frequency response nor the bandwidth of the system is calibrated and measured.
      The main difficulty of measuring its bandwidth is that the sensed signal of the
      conductance catheter system, which can be viewed as the input of the system, is a
      modulated signal, rather than a typical sin wave. Therefore, its bandwidth cannot
      be measured by typical frequency response analyzers, since they are designed for
      pure sin-wave input. The waveform of the sensed signal is analyzed. Moreover, a
      waveform simulator designed to mimic the sensed signal is presented. It can be
      used to measure the bandwidth of conductance catheter system.

PMID- 19163806
TI  - Radar mechanocardiography: a novel analysis of the mechanical behavior of the
      heart.
AB  - In this paper a novel system for detection of the mechanical movement of heart,
      mechanocardiography (MCG), with no connection to the subject's body is presented.
      This signal is based on radar technology. The acquired signal is highly
      correlated to the acceleration-based ballistocardiograph signal (BCG) recorded
      directly from the sternum. It is shown that the heart and breathing rates can be
      reliably detected using this system.

PMID- 19163807
TI  - Heart sound and electrocardiogram recording devices for telemedicine
      environments.
AB  - There is currently a worldwide trend to bring healthcare services as close as
      possible to the patient, either through home healthcare systems, or telemedicine.
      There is thus a general need for equipment that can capture patient data
      electronically for automated review or analysis by a medical practitioner. This
      paper presents prototype systems that were developed with the ultimate aim for
      use in telemedicine settings in rural Africa. These devices can be used to
      electronically capture data on patients from several sensors in a quick an easy
      manner. In our presented cases we focus on cardiovascular information. One of the
      main advantages of the proposed systems is that the data are captured
      simultaneously from multiple sensors. The data can be stored and sent
      electronically for review and analysis, and knowledge-based systems or neural
      network type models can be used in the future for semi-autonomous screening of
      the recordings, before a patient is referred to a specialist.

PMID- 19163808
TI  - Optical spectroscopy on in vitro fungal diagnosis.
AB  - The growing incidence of microbial infections and the increasing ability of such
      organisms to acquire resistance to antimicrobial treatment lead the requirement
      of fast bacteria and fungi identification methods. In this work we explored
      optical spectroscopic techniques on fungal identification. We show that some
      fungal infections can be identified by ultraviolet optical excitation of fungi
      fluorescence followed by the spectral analysis of the emitted light. Moreover, we
      demonstrate that ultraviolet LED and LASER could be applied in fungal
      identification and a new device for fungal diagnosis is proposed.

PMID- 19163809
TI  - A novel technological approach towards the early diagnosis of neurodevelopmental
      disorders.
AB  - In this work, a novel technological approach to the early diagnosis of neuro
      developmental disorders is presented. Disorders such as Autism are typically
      diagnosed after language development, i.e. after the 2-3 years of age. In this
      paper, three different typologies of instruments are presented which are designed
      to assess infants behavior in different perceptual and motor domains. The first
      is an instrumented toy embedding kinematic and force sensors for studying
      grasping and manipulation in infants as young as 6 months old. The second is a
      wearable device for sensing the kinematics of the upper and lower limbs of
      infants, designed to assess spontaneous movements in premature babies. The third
      is a multimodal audio-visuo-vestibular cap which was designed to assess infants
      orienting behaviors in social situations in response to audio and visual stimuli.

PMID- 19163810
TI  - A system for move-free and real time monitoring of readiness.
AB  - In this paper we propose a portable and compact system for real-time
      monitoring/assessing of individuals fatigue under active conditions based on
      measurements of eyes. Real-time monitoring of fatigue - cognitive, physiological,
      and physical - can help supervisors and commanders to prudently assign tasks so
      as to prevent human errors and causalities. The proposed system utilizes a very
      small camera mounted on the frame of eye glasses. Five parameters of human eyes
      are measured and their significant variations are reported to a monitoring center
      using the hardware installed in the helmet. The experimental results and case
      studies showed that this system can be reliably employed for move-free monitoring
      individual fatigue.

PMID- 19163811
TI  - A two-stage approach to positioning and identification of tracheal intubation
      using LED-based lightwand and acoustic models.
AB  - This paper proposes a two-stage approach to positioning and identifying tracheal
      intubations by computer-assisted diagnosis system. First, an innovated LED-based
      lightwand is developed for positioning the opening of the trachea and inserting
      the endotracheal tube rapidly. The proposed LED-based lightwand instrument
      significantly reduces the effects of temperature reaction without changing
      transillumination through the tissue. After intubation, breath sound analysis
      instrumentation is developed and assists for identifying the accurate tube
      position. To overcome the fast and overstepped variations of amplitude, a high
      sensitivity omni dimensional microphone and an automatic gain control device with
      linear phase property are calibrated and conducted into experiments of operating
      intubations. User-friendly interface software is also developed to analyze and
      transcribe the physiological characteristics of the collected breath sound
      corpus. Several subjective and objective experiments are performed to examine the
      practicability of the proposed approach and systems. The preliminary results show
      that the proposed LED-based lightwand instrument outperformed in the tip
      temperature without the influence on transillumination. The proposed parameters
      of average vibration parameter variance (AVPV) and frequency-domain energy
      variance (FEV) revealed the potential for distinguishing between the tracheal and
      esophageal intubations.

PMID- 19163812
TI  - A survey on wearable biosensor systems for health monitoring.
AB  - Wearable biosensor systems for health monitoring are an emerging trend and are
      expected to enable proactive personal health management and better treatment of
      various medical conditions. These systems, comprising various types of small
      physiological sensors, transmission modules and processing capabilities, promise
      to change the future of health care, by providing low-cost wearable unobtrusive
      solutions for continuous all-day and any-place health, mental and activity status
      monitoring. This paper presents a comprehensive survey on the research and
      development done so far on wearable biosensor systems for health-monitoring, by
      comparing a variety of current system implementations and approaches and
      identifying their technological shortcomings. A set of significant features, that
      best describe the functionality and the characteristics of wearable biosensor
      systems, has been selected to derive a thorough study. The aim of this survey is
      not to criticize, but to serve as a reference for current achievements and their
      maturity level and to provide direction for future research improvements.

PMID- 19163813
TI  - Preliminary study on physiological changes of hemorrhagic shock in rats.
AB  - Hemorrhagic shock is a common cause of death in emergency rooms. The objective
      evaluation of hemorrhagic shock is very important for early diagnosis and
      treatment. The purpose of this study is to understand its mechanism by analyzing
      the changes of bio-signals in hemorrhagic shock using controlled hemorrhage of
      Sprague-Dawley rats. We constructed an integrated system to be able to control
      bleeding and to simultaneously measure bio-signals such as ECG, blood pressure,
      temperature, and respiration. In order to verify the system, we measured the bio
      signals mentioned above while hemorrhagic shock was induced by withdrawing blood
      (2.5 ml / 100 g / 15 min) from a femoral vein for 10 rats.

PMID- 19163814
TI  - Radial artery pulse wave simulator using a linear motor.
AB  - To reproduce radial artery pulse wave, electronic simulator was developed. The
      microprocessor regenerates arterial pulse waveform based on the measured human
      arterial pulse data. The radial artery pulse wave could be generated from
      magnetic force using a linear motor. It was also confirmed that developed pulse
      simulator generated adaptive amplitude depend on the applied pressure on the
      surface of actuator. It is also necessary to update and extend pulse wave
      database for many cases and symptoms.

PMID- 19163815
TI  - A prototype wireless inertial-sensing device for measuring toe clearance.
AB  - Tripping and slipping are serious health concerns for the elderly because they
      result in life threatening injuries i.e., fractures and high medical costs. Our
      recent work in detection of tripping gait patterns has demonstrated that minimum
      toe clearance (MTC) is a sensitive falls risk predictor. MTC measurement has
      previously been done in gait laboratories and on treadmills which potentially
      imposes controlled walking conditions. In this paper, we describe a prototype
      design of a wireless device for monitoring vertical toe clearance. The sensors
      consists of a tri-axis accelerometer and dual-axis gyroscope connected to
      Crossbow sensor motes for wireless data transmission. Sensor data are transmitted
      to a laptop and displayed on a Matlab graphic user interface (GUI). We have
      performed zero base and treadmill experiments to investigate sensor performance
      to environmental variations and compared the calculated toe clearance against
      measurements made by an Optotrak motion system. It was found that device outputs
      were approximately independent of small ambient temperature variations, had a
      reliable range of 20m indoors and 50m outdoors and a maximum transmission rate of
      20 packets/s. Toe clearance measurements were found to follow the Optotrak
      measurement trend but could be improved further by dealing with double
      integration errors and improving data transmission rates.

PMID- 19163816
TI  - Design and development of a foot position tracking device.
AB  - In this study, we developed two types of sensors which can detect foot position
      of monoplegia patient during walking practice on the gait training equipment and
      compared their accuracy and performance. The first one is based on one
      dimensional laser sensor array and load cell sensors and the foot position is
      decided by analyzing the signals from these sensors. The second one consists of a
      two-dimensional magnetic sensor array and a magnet shoe and the foot position can
      be detected by analyzing the signal from the two-dimensional magnetic sensor
      array. The comparison results show that the two-dimensional magnetic sensor array
      is more stable and robust in practical operating condition. Also, it showed that
      the conventional expensive foot pressure sensors which are widely used to detect
      foot position can be replaced by the two-dimensional magnetic sensor array.

PMID- 19163817
TI  - Characterisation of a multi-frequency wound impedance mapping instrument.
AB  - A new instrument has been developed enabling clinicians to map and study the
      healing process of a wound. Early assessment of the instrument demonstrated
      promising results both during bench testing as well as during initial in vivo
      measurements on a skin abrasion. Clear differences between healthy and wounded
      tissue were demonstrated and a pattern was observed, potentially indicative of
      the healing process for this particular wound.

PMID- 19163818
TI  - A power-efficient analog integrated circuit for amplification and detection of
      neural signals.
AB  - We present a neural amplifier that optimizes the trade-off between power
      consumption and noise performance down to the best so far reported. In the
      perspective of realizing a fully autonomous implantable system we also address
      the problem of spike detection by using a new simple algorithm and we discuss the
      implementation with analog integrated circuits. Implemented in 0.35-microm CMOS
      technology and with total current consumption of about 20 microA, the whole
      circuit occupies an area of 0.18 mm(2). Reduced power consumption and small area
      make it suited to be used in chronic multichannel recording systems for neural
      prosthetics and neuroscience experiments.

PMID- 19163819
TI  - Estimation of respiratory waveform and heart rate using an accelerometer.
AB  - In this paper the use of an accelerometer to measure cardio-respiratory activity
      is presented. Movement of the chest was recorded by an accelerometer attached to
      a belt around the chest. The acquisition is realized in different status: normal,
      apnea, deep breathing or after exhaustion and also in different postures:
      vertical (sitting, standing) or horizontal (lying down). The resulting signal was
      compared with reference measurements. The results of experimental evaluation
      indicate that using a chest-accelerometer can correctly detect the respiratory
      waveform and heart rate (HR) signal. This method is therefore suitable for
      automatic identification some disease, for example arrhythmia or sleep apnea.

PMID- 19163820
TI  - Detecting idiopathic toe-walking gait pattern from normal gait pattern using heel
      accelerometry data and Support Vector Machines.
AB  - Toe walking is commonly seen in children with neurological symptoms such as
      cerebral palsy. However idiopathic toe walking (ITW) in children is considered to
      be habitual. ITW children are categorized as toe walkers without any neurological
      problems, however they walk with their foot plantar-flexed. These children often
      suffer poor sport performance leading to low exercise levels and the associated
      consequences. If the condition is not treated, the ITW children eventually
      develop abnormal gait pattern as adults and could suffer from postural problems.
      However, ITW gait is difficult to observe since children can modify their gait
      when made aware of it. Gait analysis using heel accelerometry data in ITW
      children could provide an objective and quantitative description of their toe
      walking and may thus be beneficial for observing ITW. In this paper, we propose a
      technique based on Support Vector Machines (SVM) to recognize ITW gait patterns
      using heel accelerometry data. Test results indicated that the SVM is able to
      identify ITW gait patterns with a maximum accuracy of 87.5% when a feature
      selection algorithm was applied.

PMID- 19163821
TI  - Development of acupoints discrimination system using electric properties of
      acupoints and non-acupoints.
AB  - The conventional acupuncture-point stimulus pattern uses direct current (DC) to
      discriminate acupuncture point and meridian lines, which are fundamental to
      diagnosis and treatment in Oriental medicine. However, DC is insufficiently
      reliable in discriminating these acupuncture points and lines. To overcome these
      problems, the authors extracted optimal parameters (e.g., square-like waveform
      with a frequency of 3 to approximately 5 kHz) with a single power alternating
      current (SPAC) stimulus pattern of 1.28V. The SPAC stimulus pattern has little or
      no effect on cells and the body's physiological state and minimizes polarization
      and ionization of cells because it uses low voltage and alternating current. The
      authors developed a new meridian discrimination system that can be used with the
      SPAC.

PMID- 19163822
TI  - Relationship between adaptation of motor control and cognition of environmental
      dynamics.
AB  - This paper considers the analysis of dynamics of human operators when the
      environmental dynamics changes. When an operator conducts a task with his arm,
      the adaptation on his manipulating dynamics occurs according to the dynamics of
      environment. We assume that the adaptation has a certain relation to the
      cognition of the change of environmental dynamics. To confirm the assumption, we
      have planned the experiment in which subjects are required to perform several
      kinds of tracking tasks. It is shown in the experiment that the dynamics of
      manipulation correlates with the cognition of the change of environmental
      dynamics.

PMID- 19163823
TI  - Glucose Minimal Model population analysis: likelihood function profiling via
      Monte Carlo sampling.
AB  - Population kinetic modeling approaches, implemented as nonlinear mixed effects
      models, are attracting growing interest in many fields of biomedicine thanks to
      their value in estimating population features from sparsely sampled data.
      However, their application often entails approximations of the original model
      function, whose effect is difficult to gauge in general. We apply negative log
      likelihood profiling to assess the effect of model approximation on the glucose
      insulin Minimal Model, and compare nonlinear mixed-effects approximate methods to
      two-stage methods. Our preliminary findings suggest that nonlinear mixed effects
      models provide accurate parameter estimates, but also point out that the
      reliability of such estimates may be affected by large population variability and
      small sample size.

PMID- 19163824
TI  - Estimation and presentation of blood flow and velocity from angiographic scans in
      the human cerebral arterial system.
AB  - This paper provides an overview of blood flow in the arterial system and aims to
      estimate the blood velocity from cerebral angiography scans without having
      acquired data on velocity by using Murray's Law. The estimation technique post
      processes the scan and provides crucial 3D visual data for the development of a
      visualization program of the blood flow in the human brain.

PMID- 19163825
TI  - Control of the transition to long-term nonprogressor in tristable HIV dynamics.
AB  - The human immunodeficiency virus (HIV) infection, that causes acquired immune
      deficiency syndrome (AIDS), is a dynamic process that can be modeled via
      differential equations. In this paper we apply a control strategy to boost the
      immune response for a tristable HIV dynamic model. The purpose of this control
      method is to steer the system to an equilibrium condition known as long-term
      nonprogressor, which corresponds to an infected patient that does not develop the
      symptoms of AIDS. The control strategy is implemented by controlled drug
      scheduling based on the understanding of the immune boosting mechanism. The
      feasibility of the methodology is illustrated via simulations.

PMID- 19163827
TI  - Characterization of iris pattern stretches and application to the measurement of
      roll axis eye movements.
AB  - Eye movements are utilized in many scientific studies as a probe that reflects
      the neural representation of 3 dimensional extrapersonal space. This study
      proposes a method to accurately measure the roll component of eye movements under
      the conditions in which the pupil diameter changes. Generally, the iris pattern
      matching between a reference and a test iris image is performed to estimate roll
      angle of the test image. However, iris patterns are subject to change when the
      pupil size changes, thus resulting in less accurate roll angle estimation if the
      pupil sizes in the test and reference images are different. We characterized non
      uniform iris pattern contraction/expansion caused by pupil dilation/constriction,
      and developed an algorithm to convert an iris pattern with an arbitrary pupil
      size into that with the same pupil size as the reference iris pattern. It was
      demonstrated that the proposed method improved the accuracy of the measurement of
      roll eye movement by up to 76.9%.

PMID- 19163826
TI  - A model of ventilation used to interpret newborn lamb respiratory signals.
AB  - This paper presents a model-based method for the analysis of respiratory signals
      specifically adapted to newborns. The model includes a description of upper
      airways, distensible and lower airways, lungs, chest wall, alveoli, pleura and
      respiratory muscle activity. The model was used in stationary and non-stationary
      conditions to simulate respiratory signals obtained in one newborn lamb in
      various physiological conditions. An identification algorithm was used to adapt
      the model parameters to lamb data. Finally, the identified parameters were
      compared to values previously reported in adult humans.

PMID- 19163828
TI  - Understanding virulence mechanisms in M. tuberculosis infection via a circuit
      based simulation framework.
AB  - Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), is a
      growing international health crisis. Mtb is able to persist in host tissues in a
      non-replicating persistent (NRP) or latent state. This presents a challenge in
      the treatment of TB. Latent TB can re-activate in 10% of individuals with normal
      immune systems, higher for those with compromised immune systems. A quantitative
      understanding of latency-associated virulence mechanisms may help researchers
      develop more effective methods to battle the spread and reduce TB associated
      fatalities. Leveraging BioXyce's ability to simulate whole-cell and multi
      cellular systems we are developing a circuit-based framework to investigate the
      impact of pathogenicity-associated pathways on the latency/reactivation phase of
      tuberculosis infection. We discuss efforts to simulate metabolic pathways that
      potentially impact the ability of Mtb to persist within host immune cells. We
      demonstrate how simulation studies can provide insight regarding the efficacy of
      potential anti-TB agents on biological networks critical to Mtb pathogenicity
      using a systems chemical biology approach.

PMID- 19163829
TI  - Enhancement of information transmission with stochastic resonance in hippocampal
      CA1 neuron network.
AB  - Stochastic resonance (SR) has been shown to improve the detection of subthreshold
      neural signals in uncorrelated noise. It is yet unclear if and how interactions
      within a population of neurons can improve information processing in neural
      networks. In this paper, we investigate the effect of the number of neurons on
      information transmission in an array of hippocampal CA1 neuron models, i.e.,
      array-enhanced SR (AESR). In computer simulations, the sub-threshold synaptic
      current (signal) generated by a filtered homogeneous Poisson process was applied
      to a distal position in each of the apical dendrites, while the background
      synaptic currents (uncorrelated noise) were presented to a proximal or middle
      point in each of the dendrites. The transmembrane potentials were recorded at one
      of the somas in the array of CA1 neuron models, in order to find spike firings
      and likewise to estimate the total and noise entropies calculated from those
      spike firing times. The results show that the information rate estimated at the
      population of the CA1 neuron models is maximized at a specific amplitude of
      uncorrelated noise, implying AESR. The results further show that the maximum
      information rate is increased as the number of neurons is increased. It is
      concluded that AESR can be an important role in information processing is neural
      systems and that the AESR is modulated by the number of neurons within the
      network.

PMID- 19163830
TI  - Event-based detection of lapses of responsiveness.
AB  - EEG spectral power has been shown to correlate with level of arousal and
      alertness in humans. In this paper, we assess its usefulness in the detection of
      lapses of responsiveness ('lapses') on an event, rather than state, basis. Eight
      non-sleep-deprived normal subjects performed two 1-hour sessions of a continuous
      tracking task while EEG and facial video were recorded. Lapses were identified by
      the presence of tracking flat spots or clear instances of behavioural microsleeps
      as identified by a human rater observing video recordings of the subject.
      Spectral power in the standard EEG bands was calculated using the Burg method on
      16 bipolar derivations to form an EEG feature matrix. Linear discriminant
      analysis was used to form a classifier for each subject. The 8 classifiers were
      combined using stacked generalization with constrained-least squares fitting to
      create an overall detection model. Estimation of lapse-event detection
      performance required the development of a novel procedure to account for the
      variable duration of lapses. Event detection for the concatenated data from all 8
      subjects yielded an overall sensitivity of 73.5%, selectivity of 25.5%, and
      accuracy of 61.2%. While the performance of this detector is modest, and not yet
      sufficient for real-time detection, the detection of lapses at such a high
      temporal resolution (1 s) is encouraging relative to previous studies which have
      generally tended to estimate changes in alertness on a minute-scale basis.

PMID- 19163831
TI  - Localization and classification of phonemes using high spatial resolution
      electrocorticography (ECoG) grids.
AB  - We present results of cortical activity during phoneme pronunciation, recorded
      using miniaturized electrocorticography grids with high spatial resolution. A
      patient implanted with the miniature grid was instructed to audibly pronounce one
      of four phonemes. For each phoneme, we observed distinct spatial correlation
      patterns at the 3mm electrode spacing. We applied a support vector machine
      classification scheme and, for the first time, were able to distinguish discrete
      phonemes with high accuracy. In addition, we found that sub-regions of our
      miniature array were specific for distinct pairs of phonemes, showing that
      cortical phoneme processing occurs at a higher resolution than previously though.

PMID- 19163832
TI  - Changes within bursts during learning in dissociated neural networks.
AB  - We have studied the effect of imprinting a new stimulus-response (SR)
      relationship into a neuronal network cultured on a multi electrode array (MEA).
      We have used the Conditional Repetitive Stimulation (CRS) algorithm introduced by
      Shahaf et al in 2004. In this algorithm focal electrical stimulation is delivered
      at a low rate (<<1 Hz) and is withdrawn when a desired response is observed. We
      confirmed that CRS could train the network to strengthen an initially weak SR
      relationship. With the acquisition of a new SR relationship, we studied its
      effect on network activity. Specifically, spontaneously occurring network bursts
      measured before, during and after training were analyzed. The total firing rate
      within bursts was estimated with a temporal resolution of milliseconds (burst
      profiles). We have shown earlier that these profiles change shape on a time base
      of several hours during spontaneous development. We show that the rate of change
      of the profiles during training (i.e. CRS) was higher than when no stimulation
      was applied.

PMID- 19163833
TI  - Aliasing rejection in Precision Decomposition of EMG signals.
AB  - The use of Artificial Intelligence (AI) methods in Precision Decomposition (PD)
      of indwelling and surface electromyographic (EMG) signals has led to the recent
      development of systems that can automatically resolve most instances of complex
      superposition among action potentials. The remaining errors have to be corrected
      by a user-interactive editing process. Typically, 25% to 50% of such errors
      involve action-potential aliasing, whereby the action potential of a motor unit
      is incorrectly identified in signal data that actually supports the action
      potential of another motor unit. To drastically reduce this class of errors, we
      have added a new aliasing-rejection mechanism in PD algorithms. Experimental
      results on real EMG signals show that aliasing-related errors of the Precision
      Decomposition technique are thereby reduced by 80% to 90%.

PMID- 19163834
TI  - Detection of the uncomfortable loudness level by electroencephalographic data: a
      novelty detection approach using habituation correlates.
AB  - The objective fitting of hearing aids and cochlear implants in uncooperative
      patients still remains a challenge. Especially in determining the threshold of
      uncomfortable loudness which cannot be predicted from the auditory threshold. In
      this study, we propose a single sweeps processing method which employs a hybrid
      approach of adaptive frame decomposition adaptation by a tight wavelet frame and
      the gaussian novelty detection for the detection of large-scale
      electroencephalographic responses correlates of habituation in late auditory
      evoked potentials. For this, habituation is discerns as a novel event. It is
      concluded that the new approach provides a fast and reliable method in the
      discrimination of uncomfortable loudness level from comfortable loudness level.
      It can be further use in more clinically oriented studies related to an objective
      frequency specific fitting of hearing aids or cochlear implants.

PMID- 19163835
TI  - EEG spectral changes and onset of burst suppression pattern in
      propofol/remifentanil anesthesia.
AB  - This paper studies how remifentanil, a commonly used intraoperative opioid,
      affects the relation of the onset of burst suppression pattern (BSP) and the
      spectral changes of EEG during anesthesia. The onsets of BSP were detected using
      both manual and the automatic method proposed from the EEGs of twenty-seven
      patients who had received different amount of remifentanil with the anesthetic.
      The spectral changes were determined by calculating the frequency progression
      patterns of the EEGs. The results showed that remifentanil significantly affects
      the relation of EEG spectral changes and the onset of BSP. The finding is
      important since the current EEG-based assessment of the depth of anesthesia
      basically relies on the analysis of the spectral features and BSP.

PMID- 19163836
TI  - Characterisation of heart rate changes and their correlation with EEG during
      neonatal seizures.
AB  - The effect of seizures on instantaneous HR (iHR) in 12 neonates is investigated
      here. HR can be readily extracted from the ECG and can be employed as an
      additional signal in seizure detection algorithms. The change in instantaneous HR
      and its correlation with the change in RMS EEG amplitude were examined. Two
      methods were employed to classify significant iHR changes. Significant
      correlation (p 0.05) during seizure was observed in 100% of patients (83.33% of
      seizures). Overall, significant iHR changes (classified by either method) were
      found in 83% of patients (50% of seizures). It was found that a markedly higher
      iHR was observed in patients whose seizures were not classified as having
      significant iHR changes.

PMID- 19163837
TI  - Detecting EEG evoked responses for target image search with mixed effect models.
AB  - There is evidence that brain signals associated with perceptual processes can be
      used for target image search. We describe the application of mixed effect models
      (MEMs) to brain signature detection. We develop an MEM detector for detecting
      brain evoked responses generated by perceptual processes in the human brain
      associated with detecting novel target stimuli. We construct the model using
      principal component analysis and linear discriminant analysis (LDA) bases. We
      adopt the LDA for dimension reduction. For parameter regularization we use 10
      fold cross validation and report experimental results from six subjects. Four out
      of six subjects achieve very good detection performance with more than 0.9 areas
      under receiver operating characteristic curves. The results demonstrate that the
      MEM can provide reliable inference on single-trial ERP detection on the task of
      target image search.

PMID- 19163839
TI  - Tracking temporal evolution of nonlinear dynamics in hippocampus using time
      varying volterra kernels.
AB  - Hippocampus and other parts of the cortex are not stationary, but change as a
      function of time and experience. The goal of this study is to apply adaptive
      modeling techniques to the tracking of multiple-input, multiple-output (MIMO)
      nonlinear dynamics underlying spike train transformations across brain
      subregions, e.g. CA3 and CA1 of the hippocampus. A stochastic state point process
      adaptive filter will be used to track the temporal evolutions of both feedforward
      and feedback kernels in the natural flow of multiple behavioral events.

PMID- 19163838
TI  - Study on mental stress using near-infrared spectroscopy, electroencephalography,
      and peripheral arterial tonometry.
AB  - In this research, we used near-infrared spectroscopy (NIRS) as an alternative
      technique for mental state analysis, and compared its performance with other
      conventional techniques such as electroencephalography (EEG) and peripheral
      arterial tonometry (PAT) during stress and healing tasks. We measured biological
      signals simultaneously in our experiments using these techniques for comparison.
      NIRS results showed that the level of total hemoglobin in the frontal cortex
      increased during a stress task and decreased during a healing task for all
      subjects whose blood volume change was properly recorded. EEG, however, showed
      inconsistent results due to task variation. Only PAT gave consistent results in
      many of the subjects. Taken together, the results suggest that NIRS might be
      suitable for mental state evaluation, with PAT as an alternative.

PMID- 19163840
TI  - Estimating vigilance in driving simulation using probabilistic PCA.
AB  - In avoiding fatal consequences in accidents behind steering wheel caused by low
      level vigilance, EEG has shown bright prospects. In this paper, we propose a
      novel method for discriminating two different vigilance states of the subjects,
      namely wake state and sleep state, during driving a car in a simulation
      environment. After filtering the EEG data into a specific frequency band, we use
      probabilistic principle component analysis (PPCA) to reduce the data dimension.
      Then we model each vigilance state as a lower dimension Gaussian random variable
      by applying PPCA again. The feature related to class posterior probability is
      calculated for classification. The experimental results show satisfying time
      resolution (< or = 5s) and high accuracy (> or = 96%) across five subjects on
      both common frequency bands beta (19-26 Hz) and gamma (38-42 Hz), and a broad
      band (8-30 Hz).

PMID- 19163841
TI  - Assessment of computerized analysis algorithms for one dimension physiologic data
      with multiple databases.
AB  - Software technology enables computerized analysis to offer second opinion in
      various screening and diagnostic tasks to assist the clinicians. Yet, the
      performance of these computerized methods for medical images is questioned by
      experts in CAD research, owing to the use of different databases and criteria for
      evaluating the computer results for comparison. This paper intends to
      substantiate this statement by illustrating the effects of such issues with the
      use of 1D physiologic data and multiple databases. For this purpose, the
      detection of desaturation events in Sp02 and spike events in EEG are used. This
      is the first time that comparison between different algorithms on a common basis
      is carried out on an individual effort. The appraisal for all the algorithms is
      made on the same databases and criteria. It is surprising to find that issues for
      2/3D images concur with those found in 1D data here. In evaluating the accuracy
      of a new algorithm, a single independent database gives results fast. This paper
      reveals weaknesses of such an approach. It is hoped that the supportive evidence
      shown here is enough for researchers to innovate a better platform for
      credibility in reporting performance comparison of computerized analysis
      algorithms.

PMID- 19163842
TI  - A novel method for characterization of peripheral nerve fiber size distributions
      by group delay measurements and simulated annealing optimization.
AB  - The ability to determine the characteristics of peripheral nerve fiber size
      distributions would provide additional information to clinicians for the
      diagnosis of specific pathologies of the peripheral nervous system. Investigation
      of these conditions, using electro-diagnostic techniques, is advantageous in the
      sense that such techniques tend to be minimally invasive yet provide valuable
      diagnostic information. One of the principal electro-diagnostic tools available
      to the clinician is the nerve conduction velocity test. While the peripheral
      nerve conduction velocity test can provide useful information to the clinician
      regarding the viability of the nerve under study, it is a single parameter test
      that yields no detailed information about the characteristics of the functioning
      nerve fibers within the nerve trunk. In this study we present a technique based
      on a decomposition of the maximal compound evoked potential and subsequent
      determination of the group delay of the contributing nerve fibers. The fiber
      group delay is then utilized as an initial estimation of the nerve fiber size
      distribution and the concomitant temporal propagation delays of the associated
      single fiber evoked potentials to a reference electrode. Subsequently the
      estimated single fiber evoked potentials are optimized against the template
      maximal compound evoked potential using a simulated annealing algorithm.
      Simulation studies, based on deterministic single fiber action potential
      functions, are used to demonstrate the robustness of the proposed technique in
      the presence of noise associated with variations in distance between the nerve
      fibers and the recording electrodes between the two recording sites.

PMID- 19163843
TI  - Comparison of spike-sorting algorithms for future hardware implementation.
AB  - Applications such as brain-machine interfaces require hardware spike sorting in
      order to (1) obtain single-unit activity and (2) perform data reduction for
      wireless transmission of data. Such systems must be low-power, low-area, high
      accuracy, automatic, and able to operate in real time. Several detection and
      feature extraction algorithms for spike sorting are described briefly and
      evaluated in terms of accuracy versus computational complexity. The nonlinear
      energy operator method is chosen as the optimal spike detection algorithm, being
      most robust over noise and relatively simple. The discrete derivatives method [1]
      is chosen as the optimal feature extraction method, maintaining high accuracy
      across SNRs with a complexity orders of magnitude less than that of traditional
      methods such as PCA.

PMID- 19163844
TI  - The 3D position estimation of neurons in the hippocampus based on the multi-site
      multi-unit recordings with silicon tetrodes.
AB  - The mechanical strain of the neural tissue induced by the implant of neuronal
      electrode is one of the important factors responsible for the quality and
      performance of extracellular recording of neuronal activities in the brain
      because the mechanical strain could kill or inactivate the neurons. In order to
      evaluate the effect of the implant of neural electrode, we propose a method to
      estimate the three-dimensional distribution of electrophysiologically active
      neurons near the electrode based on the multi-site multi-unit recording data. The
      spatial distribution of the active neurons emerges the region in the neural
      tissue that could be killed or inactivated by the implant of the electrode. The
      proposed method will be useful for the in situ assessment of the neural electrode
      implanted in the brain.

PMID- 19163845
TI  - Optimal path-following control of a smart powered wheelchair.
AB  - This paper proposes an optimal path-following control approach for a smart
      powered wheelchair. Lyapunov's second method is employed to find a stable
      position tracking control rule. To guarantee robust performance of this
      wheelchair system even under model uncertainties, an advanced robust tracking is
      utilised based on the combination of a systematic decoupling technique and a
      neural network design. A calibration procedure is adopted for the wheelchair
      system to improve positioning accuracy. After the calibration, the accuracy is
      improved significantly. Two real-time experimental results obtained from square
      tracking and door passing tasks confirm the performance of proposed approach.

PMID- 19163846
TI  - NEUSORT2.0: a multiple-channel neural signal processor with systolic array buffer
      and channel-interleaving processing schedule.
AB  - An emerging class of neuroprosthetic devices aims to provide aggressive
      performance by integrating more complicated signal processing hardware into the
      neural recording system with a large amount of electrodes. However, the
      traditional parallel structure duplicating one neural signal processor (NSP)
      multiple times for multiple channels takes a heavy burden on chip area. The
      serial structure sequentially switching the processing task between channels
      requires a bulky memory to store neural data and may has a long processing delay.
      In this paper, a memory hierarchy of systolic array buffer is proposed to support
      signal processing interleavingly channel by channel in cycle basis to match up
      with the data flow of the optimized multiple-channel frontend interface
      circuitry. The NSP can thus be tightly coupled to the analog frontend interface
      circuitry and perform signal processing for multiple channels in real time
      without any bulky memory. Based on our previous one-channel NSP of NEUSORT1.0
      [1], the proposed memory hierarchy is realized on NEUSORT2.0 for a 16-channel
      neural recording system. Compared to 16 of NEUSORT1.0, NEUSORT2.0 demonstrates a
      81.50% saving in terms of areaxpower factor.

PMID- 19163847
TI  - A simulation study assessing the efficiency of deriving evoked responses using
      high stimulus rate.
AB  - This study investigates the effects of stimulus rate on the recording efficiency
      of evoked-response scenario using a computer generated data simulating auditory
      evoked potentials (AEPs). We examine AEPs derived from three paradigms: 1)
      Conventional stimuli for ensemble averaging; 2) continuous loop averaging
      deconvolution (CLAD); and 3) maximum length sequence (MLS) stimuli, in which
      deconvolution techniques are incorporated to retrieve the overlapped responses.
      The performance is evaluated by correlation coefficients between the ideal and
      the derived responses. The results show that there is no distinct improvement of
      SNR for high rate stimulation paradigms, suggesting that the techniques of
      deconvolution in high rate will not provide more efficient recording approach.
      Further, responses from the CLAD paradigm tend to deteriorate compared to the
      other two methods due to the lower jittering arrangement of the sequence.

PMID- 19163848
TI  - Harmonic coupling of steady-state visual evoked potentials.
AB  - Steady-state visual evoked potentials (SSVEPs) are oscillating components of the
      electroencephalogram (EEG) that are detected over the occipital areas, having
      frequencies corresponding to visual stimulus frequencies. SSVEPs have been
      demonstrated to be reliable control signals for operating a brain-computer
      interface (BCI). This study uses offline analyses to investigate the
      characteristics of SSVEP harmonic amplitude and phase coupling and the impact of
      using this information to construct a matched filter for continuously tracking
      the signal.

PMID- 19163849
TI  - Quantitative evaluation of ocular artifact removal methods based on real and
      estimated EOG signals.
AB  - We propose a novel metric for quantitatively evaluating ocular artifact (OA)
      removal methods on real electroencephalogram (EEG) data. For real EEG, existing
      metrics measure the amount of artifact removed. Our metric measures how much a
      given method is likely to distort the underlying EEG. The new metric was used to
      evaluate two existing OA removal algorithms that use the electro-oculogram (EOG)
      as a reference signal. The combination of a previous metric and our new metric
      showed there is a trade-off between how well an algorithm removes OAs and how
      likely it is to distort the underlying EEG. These algorithms require a reference
      EOG signal, yet for certain applications (e.g., a brain computer interface or
      BCI) it is preferable or necessary to avoid attaching electrodes around the eyes.
      We thus also used various combinations of up to 55 channels of EEG to estimate
      the EOG reference. The metric was again used to compare the use of estimated vs.
      measured EOG. Our initial results showed that using EOG estimated from as few as
      4 EEG electrodes increased the likelihood of distorting the EEG from 14% to 19%
      and from 21% to 23% for the two algorithms. For some applications (e.g., BCI),
      the slight reduction in performance may be acceptable in order to avoid using EOG
      electrodes.

PMID- 19163850
TI  - Simultaneous measurement of force and muscle fatigue using frequency-band wavelet
      analysis.
AB  - Static and dynamic handgrip experiments are performed in order to evaluate the
      effectiveness of utilizing frequency-band wavelet analysis in measuring force and
      muscle fatigue simultaneously. SEMG signals are recorded from flexor muscle and
      analyzed using continuous wavelet transform (CWT). The wavelet coefficients are
      grouped into high frequency (65Hz - 350Hz) and low frequency (5Hz - 45Hz) band. A
      significant correlation is discovered between amplitude of high frequency band
      and force level. On the other hand, the amplitude of low frequency band is
      associated with muscle fatigue. These results have an important implication for
      estimating force and muscle fatigue simultaneously especially during dynamic
      contraction.

PMID- 19163851
TI  - Fuzzy discriminant analysis based feature projection in myoelectric control.
AB  - The myoelectric signal (MES) from human muscles is usually utilized as an input
      to the controller of a multifunction prosthetic hand. In such a system, a pattern
      recognition approach is usually employed to discriminate between the MES from
      different classes. Since the MES is recorded using multi channels, the feature
      vector size can become very large. In order to reduce the computational cost and
      enhance the generalization capability of the classifier, a dimensionality
      reduction method is needed to identify an informative moderate size feature set.
      This paper proposes a novel feature projection technique based on a combination
      of Fisher's Linear Discriminant Analysis (LDA), and Fuzzy Logic. The new method,
      called FLDA, assigns different membership degrees to the data points thus
      reducing the effect of overlapping points in the discrimination process.
      Furthermore, the concept of Mutual Information (MI) is introduced in the fuzzy
      memberships in order to assign weights to the features (attributes) according to
      their contribution to the discrimination process. The FLDA method is tested on a
      seven classes MES dataset and compared with other feature projection techniques
      proving its superiority.

PMID- 19163852
TI  - Analysis of dynamic EMG and acceleration measurements in Parkinson's disease.
AB  - In this paper, we bring out modern methods that are potential in analysing
      differences in the dynamic surface electromyographic (EMG) and acceleration
      measurements between patients with Parkinson's disease (PD) and healthy persons.
      These methods are the correlation dimension of EMG, the recurrence rate of EMG,
      the power of acceleration and the sample entropy of acceleration. In this study,
      these methods were used to extract features from surface EMG and acceleration
      recordings measured during elbow flexion and extension movements. The extracted
      features were used to form high-dimensional feature vectors and the
      dimensionality of these vectors was then reduced by using the principal component
      approach. Finally, the feature vectors were discriminated between subjects by
      using the principal components. The discrimination power of the presented
      approach was tested with EMG and acceleration data measured from 46 patients with
      PD (on-medication) and 59 healthy controls. Discrimination results showed that
      the present method was able to discriminate dynamic EMG and acceleration
      recordings between patients with PD and healthy controls. Therefore, dynamic
      surface EMG and acceleration measurements may have potential in the objective and
      quantitative assessment and diagnosis of PD.

PMID- 19163853
TI  - Intrinsic mode entropy: an enhanced classification means for automated Greek Sign
      Language gesture recognition.
AB  - Sign language forms a communication channel among the deaf; however, automated
      gesture recognition could further expand their communication with the hearers. In
      this work, data from three-dimensional accelerometer and five-channel surface
      electromyogram of the user's dominant forearm are analyzed using intrinsic mode
      entropy (IMEn) for the automated recognition of Greek Sign Language (GSL)
      gestures. IMEn was estimated for various window lengths and evaluated by the
      Mahalanobis distance criterion. Discriminant analysis was used to identify the
      effective scales of the intrinsic mode functions and the window length for the
      calculation of the IMEn that contributes to the correct classification of the GSL
      gestures. Experimental results from the IMEn analysis of GSL gestures
      corresponding to ten words have shown 100% classification accuracy using IMEn as
      the only classification feature. This provides a promising bed-set towards the
      automated GSL gesture recognition.

PMID- 19163854
TI  - Classification of upper arm EMG signals during object-specific grasp.
AB  - Electromyographic (EMG) signals can represent an interesting solution to control
      artificial hands because they are easy to record and can allow the user to
      control different robotic systems. However, after limb amputation the
      'homologous' muscles are no more available to control the prosthetic device and
      for this reason complex pattern recognition approaches have to be developed to
      extract the voluntary commands by the user. This makes the control strategy less
      natural and acceptable and asks for alternative approaches. At the same time, it
      has been recently shown that (in monkeys) it is possible to discriminate grasping
      tasks just analyzing the activation onset/offset of upper limb muscles during the
      reaching phase. This kind of information can be very interesting because it can
      allow the development of a natural EMG-based control strategy based on the
      natural muscular activities selected by the central nervous system. In this
      paper, preliminary experiments have been carried out in order to verify whether
      these results can be confirmed also in human beings. In particular, a support
      vector machine (SVM) based pattern recognition algorithm has been developed and
      used for the prediction of grip types from the EMG recorded from proximal and
      distal muscles during reach to grasp movements of three able bodied subjects.

PMID- 19163855
TI  - Estimation of tendon slack lengths of quadriceps based on a least squares
      optimization.
AB  - Based on the force transfer relationship from muscle to tendon, a chart
      determining a normalized tendon force is developed. The experimental data of knee
      extension moment obtained at maximum isometric contractions are prepared to
      characterize one's musculo-tendon properties. An optimization algorithm is
      introduced, which searches the tendon slack lengths of quadriceps by minimizing
      the differences of calculated knee extension moment with experimental data. The
      optimized results which are obtained using various search range limit are
      summarized and analyzed.

PMID- 19163856
TI  - Walking pattern analysis and SVM classification based on simulated gaits.
AB  - Three classes of walking patterns, normal, caution and danger, were simulated by
      tying elastic bands to joints of lower body. In order to distinguish one class
      from another, four local motions suggested by doctors were investigated stepwise,
      and differences between levels were evaluated using t-tests. The human
      adaptability in the tests was also evaluated. We improved average classification
      accuracy to 84.50% using multiclass support vector machine classifier and
      concluded that human adaptability is a factor that can cause obvious bias in
      contiguous data collections.

PMID- 19163857
TI  - A study on balance maintenance strategies during walking - a simulation study.
AB  - Walking assist systems should cope with both the external perturbation caused by
      slips, uneven terrain, slopes, and obstacles, and local function impairment
      caused by internal factors, like spastic paralysis. It is known that humans are
      able to cope with these difficulties by different strategies. One is that in the
      case when external perturbation occurs, especially when the occurrence cannot be
      predicted or perceived in advance, humans rely on reflexes, which cause
      unconscious, relatively fixed muscular response patterns to perturbations within
      a short period of time. Another is that in the case of local function impairment,
      humans generally develop compensated gait to overcome the falling-down risky
      factors. In this study, we investigated the both strategies by constructing a
      human walking model that consists of Central Pattern Generator (CPG) module. As
      the reflexive mechanism, we used muscle activity profiles acquired from human
      gait experiments, together with a CPG-phase-modulation, and we examined of the
      roles of these two reflexive mechanisms. Besides, we modeled a spastic hemiplegic
      gait by modulating some specific neuron's output, in order to study another
      strategy, compensated walking. The results indicated that the simulation model
      could display behavior resembling that of normal human walking, and on the
      occurrence of a slip-perturbation, together with the CPG-phase-modulation, the
      rapid muscular response could improve perturbation-resistance and maintain
      balance for the simulated walker. Moreover, the pes equinus caused by the
      spasticity in Gastrocnemius could be modelled and falling down risk resulted from
      the pes equinus could be reduced by the simulated compensated walking.

PMID- 19163858
TI  - Effect of a visual-based sensory motor task on muscle tuning during a dynamic
      balance task.
AB  - In this research, we explored visually-based sensory motor learning when a
      transformation was applied to the trajectory used to move and track a visual
      target in a virtual environment. The virtual task was controlled by the subject's
      center of foot pressure (COP), where the COP position was mapped to an on-screen
      cursor. Target balloons appeared randomly on the screen; the subject was
      instructed to move the COP-controlled cursor to intersect and burst the balloons.
      A transformation was applied to the movement trajectory, which rotated the on
      screen cursor counter-clockwise by 60 degrees . The transformation required the
      subjects to update their spatial reference coordinates between the physical COP
      position and the on-screen cursor. To investigate learning during the
      transformation, electromyogram (EMG) data was recorded from the tibialis anterior
      and peroneus longus muscles. The muscle activity, calculated as the root mean
      square (RMS) of the EMG data, was calculated for each muscle as a function of the
      movement direction during movement initiation. The preferred direction (PD) for
      each muscle was then determined as the directional sum of the RMS values. The
      results showed a shift in the preferred direction (PD) of the muscles with
      learning.

PMID- 19163860
TI  - Spectral analysis of walking improvement utilizing AR modeling.
AB  - This study analyzes the walking improvement based on 1/f fluctuations and impulse
      responses utilizing Auto-Regressive (AR) modeling. Once subjects were aware of
      the correct posture, the fluctuation of subject's both sides of the hip while
      walking was improved more rhythmic. The analysis of impulse response utilizing AR
      modeling provided clear results for the evaluation of improvement to walking
      stability. After the subjects understood their own walking condition, based on
      1/f fluctuation, and had received suitable rehabilitation and shoes, their
      walking stability improved satisfactorily. This study provides a useful method of
      medical evaluation in rehabilitation and physical fitness, and a means for
      subjects to maintain a state of well being.

PMID- 19163859
TI  - Do external stimuli, applied to train cultured cortical networks, disturb the
      balance between activity and connectivity?
AB  - Learning, or more generally, plasticity may be studied using cultured neuronal
      networks on multi electrode arrays. Many protocols have been proposed to change
      connectivity in such networks. So far, only one of these protocols, proposed by
      Shahaf and Marom, aimed to change the input-output relationship of a selected
      connection in the network. Although the results were quite promising, the
      experiments appeared difficult to repeat and the protocol did not serve as a
      basis for wider investigation yet. Here, we repeated their protocol, and compared
      our 'learning curves' to the original results. Although in some experiments the
      protocol did not seem to work, we found that on average, the protocol showed a
      significant learning effect indeed. We frequently found learning curves that
      initially declined as in the original results, but then increased again before
      finally settling at a low level.

PMID- 19163861
TI  - A novel approach using tendon vibration of the human flexor carpi radialis muscle
      to study spinal reflexes.
AB  - Although most muscle spindle investigations have used the cat model and invasive
      measurement techniques, several investigators have used microneurography to
      record from the Ia and II fibres in humans during tendon vibration. In these
      studies the muscle spindle primary endings are stimulated using transverse
      vibration of the tendon at reflex sub-threshold amplitudes. Others have used low
      amplitude vibration and the stretch evoked M-wave response to determine reflex
      properties during both agonist and antagonist voluntary contractions. In the past
      we have developed a PC based instrument that uses Labview and a linear servomotor
      to study tendon reflex properties by recording stretch evoked M-wave responses
      from single tendon taps or electrical stimuli to the afferent nerve. In this
      paper we describe a further development of this system to provide precise
      vibrations of the tendon up to 65 Hz with amplitudes up to 4 mm. The resultant M
      wave train is extracted from background noise via phase coherent subtractive
      filtering. Test results from vibrating the human distal flexor carpi radialis
      tendon at 10 and 30 Hz, for relaxed, slight flexion and slight extension, are
      also presented.

PMID- 19163862
TI  - Inherent bimanual postural synergies in hands.
AB  - This paper presents a numerical approach to prove the existence of inherent
      bimanual postural synergies while performing actions with two hands. Five
      subjects were tested in two different tasks. The first task was a well
      coordinated task where each subject screwed nut and bolt using one or both hands.
      In the second task, subjects were asked to perform several random postures with
      both hands. Joint angles were measured during the experiment by a pair of data
      gloves. Principal component analysis (PCA) was performed over the postures
      obtained during the tasks. In the first task, the number of postural synergies
      obtained for both hands together was less than the sum of the number of postural
      synergies for two hands. This is expected intuitively as first task was well
      coordinated. In the second task where there is no voluntary coordination
      involved, the number of postural synergies obtained for both hands together was
      still less than the sum of the number of postural synergies for two hands. This
      implies that there are innate bimanual synergies wired biomechanically to help
      brain in bimanual movements.

PMID- 19163863
TI  - Time course of changes in neuromuscular properties following stroke.
AB  - To characterize the natural history of stroke effects on neuromuscular properties
      in elbow muscles, we tracked changes in elbow mechanical properties in
      hemiparetic stroke survivors after stroke. Using a parallel cascade system
      identification technique, we estimated intrinsic and reflex mechanical properties
      at 1, 2, 3, 6 and 12 months post stroke. At each time point, we examined
      neuromuscular changes during variations in mean elbow joint angle. Modulation of
      intrinsic and reflex properties was assessed using small amplitude pseudorandom
      positional perturbations at different mean elbow angles, over the entire range of
      motion. We identified two patterns of stroke effects on neuromuscular properties.
      In Group 1, intrinsic stiffness increased continuously after the stroke. In Group
      2, it decreased continuously over this interval. Analogous results were recorded
      for reflex stiffness. These different recovery patterns may reflect the
      simultaneous emergence of two opposing mechanisms; i.e. brain recovery and
      secondary effects on neuromuscular properties. It follows that the progress of
      recovery may not reflect a single mechanism, and could depend on which mechanism
      is dominant at each time point.

PMID- 19163864
TI  - A footswitch evaluation of the gait of elderly fallers with and without a
      diagnosis of orthostatic hypotension and healthy elderly controls.
AB  - Gait abnormalities are a recognised risk factor for falling in the elderly and
      variability in gait has been shown to be a measurable predictor of falls. We
      carried out a footswitch evaluation of the temporal parameters of gait of elderly
      fallers with a primary diagnosis of Orthostatic Hypotension, elderly fallers
      without a diagnosis of Orthostatic Hypotension and a control group of healthy
      elderly non-fallers. We hypothesized that elderly persons with Orthostatic
      Hypotension are falling purely as a consequence of their vascular abnormalities
      and are not falling for the same reasons as regular elderly fallers, including
      biomechanical irregularities. Therefore it was assumed that their gait pattern
      would not be similar to that of regular elderly fallers but instead would
      resemble that of healthy elderly non-fallers. Results show that elderly fallers
      with or without a diagnosis of Orthostatic Hypotension tend to spend more time in
      the stance phase of gait, possibly due to a fear of falling. Elderly fallers with
      a diagnosis of Orthostatic Hypotension have similar levels of gait variability as
      healthy elderly Controls. These are significantly less than elderly fallers
      without Orthostatic Hypotension. Therefore elderly fallers with a diagnosis of
      Orthostatic Hypotension may not be falling for the same reasons as regular
      elderly fallers.

PMID- 19163865
TI  - Evolving technologies drive the new roles of Biomedical Engineering.
AB  - Rapidly changing technology coupled with the financial impact of organized health
      care, has required hospital Biomedical Engineering organizations to augment their
      traditional operational and business models to increase their role in developing
      enhanced clinical applications utilizing new and evolving technologies. The
      deployment of these technology based applications has required Biomedical
      Engineering organizations to re-organize to optimize the manner in which they
      provide and manage services. Memorial Sloan-Kettering Cancer Center has
      implemented a strategy to explore evolving technologies integrating them into
      enhanced clinical applications while optimally utilizing the expertise of the
      traditional Biomedical Engineering component (Clinical Engineering) to provide
      expanded support in technology / equipment management, device repair, preventive
      maintenance and integration with legacy clinical systems. Specifically,
      Biomedical Engineering is an integral component of the Medical Physics Department
      which provides comprehensive and integrated support to the Center in advanced
      physical, technical and engineering technology. This organizational structure
      emphasizes the integration and collaboration between a spectrum of technical
      expertise for clinical support and equipment management roles. The high cost of
      clinical equipment purchases coupled with the increasing cost of service has
      driven equipment management responsibilities to include significant business and
      financial aspects to provide a cost effective service model. This case study
      details the dynamics of these expanded roles, future initiatives and benefits for
      Biomedical Engineering and Memorial Sloan Kettering Cancer Center.

PMID- 19163866
TI  - A model for simulation of Clinical Engineering Department activities.
AB  - Clinical Engineering (CE) Departments are in charge of healthcare technology
      management in healthcare facilities. The workload is proportional to the number
      of activities, the number and complexity of biomedical instrumentation, and the
      technology intensity of the facility. Clinical engineers and Biomedical equipment
      technicians work together in order to perform the different activities and to
      obtain customer satisfaction. This paper describes a model that can be used to
      estimate the number of engineers and technicians required to start a new CE
      Department. The estimation is obtained by means of simulation. Starting by
      several inputs that describe the facility and the quantity and characteristics of
      the instruments the model is able to provide the number of Clinical engineers and
      Biomedical equipment technicians.

PMID- 19163867
TI  - A hospital registration system using syndromes' descriptions analysis and
      information retrieval technology.
AB  - Correct registration in the hospital can avoid wasting medical resources and
      shorten the time of diagnoses. The purpose of this research is to build a
      hospital registration system to help patients register in the hospital. This
      system can assist patients, who are not familiar with medical topics, to
      determine which department they should register by the spontaneous descriptions.
      Patients' spontaneous descriptions of syndromes were transcribed into text
      formation. These descriptive texts were analyzed by the keywords punctuation
      process and syndromes's descriptions analysis process to get the important
      features, including the syndrome words, degree words, affected region of body,
      frequency, time and place. Then, an information retrieval based department making
      process was employed to calculate the relation score between each department and
      these important features. Finally, the system suggested the most possible
      departments they should register to the patients. In the experiment, 50
      descriptions collected from 50 patients are as the input to the system. The
      preliminary result shows the top one correct rate is 88%. The proposed system
      also shows the higher performance than the baseline system.

PMID- 19163868
TI  - Therapy ultrasound equipment characterization: Comparison of three techniques.
AB  - Methods for characterizing ultrasonic therapy equipment rapidly and easily have
      to be implemented in order to avoid damages to patients; the existent methods
      measure different parameters in the ultrasonic beam that can be used to determine
      if the equipment works appropriately. In this paper, a comparison of three
      methods to characterize the ultrasonic beam is presented. The first one is a C
      scan with microprobe which uses a hydrophone for measuring the signal and a
      positioning system. The second method is the IR-thermography which uses a phantom
      to absorb the ultrasonic energy and to convert it into heat. Here, the heat
      distribution is obtained with an IR camera. The third method uses a sheet of
      thermochromic liquid crystals (TLC) as sensor and a phantom to absorb the energy.
      The heat distribution is obtained with a normal camera because the TLCs change
      their color as a function of temperature. The results indicate that each
      technique has its own benefits, but the most important parameters can be obtained
      with only one of them.

PMID- 19163869
TI  - Proactive medication assistances based on spatiotemporal context awareness of
      aged persons.
AB  - In this paper, we developed a system that could assist appropriate activities for
      medication adherence of the elderly. It employs a proactive knowledge which is
      represented as templates predefined for their medication activities. The
      knowledge-based assistance depends on the contexts considerably, which the system
      can recognize by continuously monitoring the current position and the time
      schedule for their medications. The monitoring is performed with ultrasonic
      sensors and infrared sensors mounted in a display and a pillbox mainly. According
      to the recognized contexts, the medication activities can he serviced through old
      person-friendly multimedia display. In special, since the knowledge is well
      defined by XML, only its content modification can provide a variety of services
      individually customized to the elderly.

PMID- 19163870
TI  - Lean Six Sigma applied to a process innovation in a mexican health institute's
      imaging department.
AB  - Delivery of services to a patient has to be given with an acceptable measure of
      quality that can be monitored through the patient's satisfaction. The objective
      of this work was to innovate processes eliminating waste and non value-added work
      in processes done at the Imaging Department in the National Institute of
      Respiratory Diseases (INER for its Spanish acronym) in Mexico City, to decrease
      the time a patient spends in a study and increase satisfaction. This innovation
      will be done using Lean Six Sigma tools and applied in a pilot program.

PMID- 19163871
TI  - Generalized Caseview applied to prostate cancer prognosis.
AB  - The interpretation of results of any study using large tables with series of
      numbers is always difficult. Generalized Case View Method (GCm) allows
      translating these tables of numbers into an image. The Method identifies each
      informational entity in the table with a 'pixel', forming what we call an
      'infoxel'. The sum of all informational entities becomes an image, the
      Generalized Caseview. The method consists of two steps: the first one is to
      define the reference frame while the second is to visualize data through the
      reference frame. The 'infoxels' that constitute the reference frame should be
      organized according to three criteria: binary, nominal and ordinal. Here this
      method has been applied to visualize the results of a study about prostate cancer
      spread. This paper exemplifies the usefulness of associating a classical
      statistical tool with Generalized Caseview method to solve a biomedical problem.

PMID- 19163872
TI  - Evaluation of a compact tinnitus therapy by electrophysiological tinnitus
      decompensation measures.
AB  - Large-scale neural correlates of the tinnitus decompensation have been identified
      by using wavelet phase stability criteria of single sweep sequences of auditory
      late responses (ALRs). Our previous work showed that the synchronization
      stability in ALR sequences might be used for objective quantification of the
      tinnitus decompensation and attention which link to Jastreboff tinnitus model. In
      this study, we intend to provide an objective evaluation for quantifying the
      effect of music therapy in tinnitus patients. We examined neural correlates of
      the attentional mechanism in single sweep sequences of ALRs in chronic tinnitus
      patients who underwent compact therapy course by using the maximum entropy
      auditory paradigm. Results by our measure showed that the extent of
      differentiation between attended and unattended conditions improved significantly
      after the therapy. It is concluded that the wavelet phase synchronization
      stability of ALRs single sweeps can be used for the objective evaluation of
      tinnitus therapies, in this case the compact tinnitus music therapy.

PMID- 19163873
TI  - Neurofeedback by neural correlates of auditory selective attention as possible
      application for tinnitus therapies.
AB  - More and more people are suffering from tinnitus. There are many treatments for
      tinnitus that have been claimed based on different causes. Unfortunately, until
      now none of the existing treatments has been found to be effective in general.
      Here, we would like to suggest a treatment to tinnitus based on neurofeedback
      using neural correlates of auditory selective evoked potentials (ASEPs). We have
      shown that the wavelet phase synchronization of auditory late responses (ALR)
      single sweeps allows for a direct online monitoring of phase locked auditory
      attention. The results show that after a simple training, subjects learned to
      control their attention to the auditory modality. To improve the ability in the
      attention control system is an objective of many tinnitus treatments, so that the
      perception of the patients towards the tinnitus noise can be reduced to a
      minimum. It is concluded that our proposed neurofeedback system by wavelet phase
      synchronization measure might be used in a clinical treatment of tinnitus
      patients and it is possible to extent to other therapeutic based control systems.

PMID- 19163874
TI  - Analysis of significant factors for dengue infection prognosis using the self
      organizing map.
AB  - This study presents a new approach to determine the significant prognosis factors
      in dengue patients utilizing the self-organizing map (SOM). SOM was used to
      visualize and determine the significant factors that can differentiate between
      the dengue patients and the healthy subjects. Bioimpedance analysis (BIA)
      parameters and symptoms/signs obtained from the 210 dengue patients during their
      hospitalization were used in this study. Database comprised of 329 sample (210
      dengue patients and 119 healthy subjects) were used in the study. Accordingly,
      two maps were constructed. A total of 35 predictors (17 BIA parameters, 18
      symptoms/signs) were investigated on the day of defervescence of fever. The first
      map was constructed based on BIA parameters while the second map utilized the
      symptoms and signs. The visualized results indicated that, the significant BIA
      prognosis factors for differentiating the dengue patients from the healthy
      subjects are reactance, intracellular water, ratio of the extracellular water and
      intracellular water, and ratio of the extracellular mass and body cell mass.

PMID- 19163875
TI  - A cooperative approach for the diagnosis of the melanoma.
AB  - In this work we present a decision support system for the melanoma diagnosis
      using individual methods and the collaboration between these methods. The system
      designed uses a photograph of the lesion and it makes a preprocessing task to
      extract the region of interest. Then, several characteristics of the image are
      analyzed, studying with different methods the degree of malignity; the methods
      used are based in Bayesian rules and in neural networks. Finally, each individual
      decision from each method contributes in some way to the final decision. The
      classification rate obtained with the cooperative approach is above 92%.

PMID- 19163876
TI  - Predicting breast cancer survivability using fuzzy decision trees for
      personalized healthcare.
AB  - Data analysis systems, intended to assist a physician, are highly desirable to be
      accurate, human interpretable and balanced, with a degree of confidence
      associated with final decision. In cancer prognosis, such systems estimate
      recurrence of disease and predict survival of patient; hence resulting in
      improved patient management. To develop such a prognostic system, this paper
      proposes to investigate a hybrid scheme based on fuzzy decision trees, as an
      efficient alternative to crisp classifiers that are applied independently.
      Experiments were performed using different combinations of: number of decision
      tree rules, types of fuzzy membership functions and inference techniques. For
      this purpose, SEER breast cancer data set (1973-2003), the most comprehensible
      source of information on cancer incidence in United States, is considered.
      Performance comparisons suggest that, for cancer prognosis, hybrid fuzzy decision
      tree classification is more robust and balanced than independently applied crisp
      classification; moreover it has a potential to adapt for significant performance
      enhancement.

PMID- 19163877
TI  - Chemotherapy side-effect management using mobile phones.
AB  - Colorectal cancer is a major health problem in developed countries, accounting
      for a significant proportion of deaths in the population. Advances in
      chemotherapy treatment have led to therapy being delivered in the home-setting,
      which presents challenges in ensuring that treatment-related side-effects are
      detected and reported to clinical staff in an appropriate time-frame. A
      telemedicine system has been developed using a mobile-phone platform to allow
      patients to complete symptom diaries which trigger alerts paged to their nurse in
      the event of severe side-effects. Six patients used this system for two cycles of
      oral chemotherapy. Two cases of moderate symptoms deteriorating to more severe
      conditions were observed, and individual self-care and treatment advice were
      presented to these patients.

PMID- 19163878
TI  - An Internet-based melanoma screening system with acral volar lesion support.
AB  - In this paper, we present an Internet-based melanoma screening system that newly
      supports acral volar lesions. A half of Asian melanomas are from these areas and
      they show completely different appearance from other lesions. Our screening
      system is accessible from all over the world and diagnoses dermoscopy images
      within 3-5 sec based on a neural network classifier for non-acral lesions or
      newly integrated linear classifier for acral volar lesions. Our system achieves a
      sensitivity of 85.9% and a specificity of 86.0% on a set of 1258 non-acral
      dermoscopy images and a sensitivity of 93.3% and a specificity of 91.1% on a set
      of 199 acral volar dermoscopy images using a leave-one-out cross-validation.

PMID- 19163879
TI  - Wireless Sensor Networks for biomedical applications in cancer hyperthermia.
AB  - In case of deep seated brain tumors or cancerous cells, focused ultrasound is
      found to be an effective treatment tool. Thermal profile under hyperthermia is
      studied here for a temperature rise of 4 to 5 degree centigrade (up to 42.5
      degree), in case of therapeutic treatment of the tumors. An in vitro tumor is
      studied with temperature sensors to understand the thermal elevation in different
      layers and different directions of the tumor. A Wireless Sensor Network (WSN ) is
      developed to transmit the tumor thermal information to an expert clinician to
      monitor the health condition and for therapeutic control of ultrasound dosage
      level, particularly in case of elderly patients living in remote areas.

PMID- 19163880
TI  - Analysis of physical activities in Taekwondo Pumsae.
AB  - Exercise is very important element for successful aging. Among many sports
      events, Korea is the suzerain of Taekwondo. When competing (Taekwondo Free
      Fighting) after learning Poomse as basic movements and inuring them, people
      compete with movements depending on situation. Among Poomses of Taekwondo,
      Taegeuk Poomse consists of very basic movements from 1 Jang to 8 Jang and they
      are for inuring to body. In order to prescribe Taegeuk Jang, which is the basic
      movement of Taekwondo that Korea is the suzerain, as an exercise for successful
      aging, it is necessary to analyze physical activity level of each Taegeuk Jang
      (From 1 Jang through 8 Jang) and suggest the same. Therefore, in this study, I
      analyzed physical activity level of each Jang of Taegeuk Poomse by attaching
      Armband made by Body Media Company on brachia and legs below knee of Taekwondo
      trainees. The result of the analysis of the whole momentum from Taegeuk 1 Jang to
      8 Jang is as follows: First, the average absolute value of acceleration variation
      of vertical direction signal (L-MAD): 5.15. Second, the average absolute value of
      acceleration variation of horizontal direction signal (T-MAD): 3.44. Finally, the
      average of calorie consumption per minute (AEE/Min): 5.06 Cal. The obtained
      result corresponds to proper exercise condition for successful aging and it can
      be utilized as data for exercise prescription for the young and the old.

PMID- 19163881
TI  - Independent component feature-based human activity recognition via Linear
      Discriminant Analysis and Hidden Markov Model.
AB  - In proactive computing, human activity recognition from image sequences is an
      active research area. This paper presents a novel approach of human activity
      recognition based on Linear Discriminant Analysis (LDA) of Independent Component
      (IC) features from shape information. With extracted features, Hidden Markov
      Model (HMM) is applied for training and recognition. The recognition performance
      using LDA of IC features has been compared to other approaches including
      Principle Component Analysis (PCA), LDA of PC, and ICA. The preliminary results
      show much improved performance in the recognition rate with our proposed method.

PMID- 19163882
TI  - Accelerometer signal-based human activity recognition using augmented
      autoregressive model coefficients and artificial neural nets.
AB  - Automatic recognition of human activities is one of the important and challenging
      research areas in proactive and ubiquitous computing. In this work, we present
      some preliminary results of recognizing human activities using augmented features
      extracted from the activity signals measured using a single triaxial
      accelerometer sensor and artificial neural nets. The features include
      autoregressive (AR) modeling coefficients of activity signals, signal magnitude
      areas (SMA), and title angles (TA). We have recognized four human activities
      using AR coefficients (ARC) only, ARC with SMA, and ARC with SMA and TA. With the
      last augmented features, we have achieved the recognition rate above 99% for all
      four activities including lying, standing, walking, and running. With our
      proposed technique, real time recognition of some human activities is possible.

PMID- 19163883
TI  - Visualizing physiological condition of two persons during cooperative motion.
AB  - The purpose of this study is to develop a visualizing system which represents
      human motion and physiological conditions such as muscle activities, autonomic
      nervous balances of multi persons simultaneously. Our system generates avatar
      animation representing muscle activity and heart rate variability of multi
      persons by color of muscles and heart. Three kinds of assistance motion were
      visualized to evaluate our system. In these experiments, muscle activity and
      heart rate variability of assisted and service persons were represented.
      Physiological conditions of multi persons are presented intuitively using this
      system. This visualizing system is useful for analysis of workload in cooperative
      motion.

PMID- 19163884
TI  - Dynamic analysis of walking stability.
AB  - Patients with walking disorders are diagnosed by orthopedics and a rehabilitation
      course in a hospital, but the walking of physically unimpaired persons is not
      diagnosed. It is considered that if they continue to walk unstably, this may
      cause lower-back pain or knee pain; this burden also exerts bad influences upon
      other physical parts. So it is important that we analyze walking stability of
      physically unimpaired persons as one aspect of preventive medicine. The center of
      gravity (COG) plays an important role in evaluation of stability for both
      standing posture and walking. In the present study, we used an acceleration
      measurement system. Using this system, we measured the acceleration displacement
      at the COG of a normal walking subject and evaluated walking stability
      quantitatively. We noted the periodicity and rhythm of the acceleration
      displacement of normal subjects while they walked, using a seasonal adjustment
      model to predict periodic fluctuations. We assessed walking stability,
      quantitatively, using the ratio of the variance of the noise component vs. the
      variance of periodic component. This study provides useful information for
      understanding walking systems in preventive medicine and rehabilitative medicine.

PMID- 19163885
TI  - Ambulatory monitoring of human posture and walking speed using wearable
      accelerometer sensors.
AB  - This paper describes a new classification system for real-time monitoring of
      physical activity, which is able to detect body postures (lying, sitting, and
      standing) and walking speed with data acquired from three wearable biaxial
      accelerometer sensors deployed in a wireless body sensor network. One sensor is
      waist-mounted while the remaining two are attached to the respective thighs. Two
      studies were conducted for the evaluation of the system, with each study
      involving five human subjects. Results from the first study indicated an overall
      accuracy of 100% for classification of lying, sitting, standing, and walking
      across a series of 40 randomly chosen tasks. In our system, estimated walking
      speeds are used to distinguish between different types of movement activity
      (walking, jogging, and running), and the accuracy of its estimation was evaluated
      in our second study which gave an overall mean-square error (MSE) of 1.76
      (km/h)(2).

PMID- 19163886
TI  - Daily activity recognition system for the elderly using pressure sensors.
AB  - As transformed to aging society rapidly, the number of old persons who live alone
      is drastically increased. Because these old people may have disorder of bodily
      function, and be suffering from geriatric disease, needs of a health assistance
      system to make them healthier are strongly increased. In this paper, we propose a
      daily activity recognition system for an old person using pressure sensors. The
      target daily activities are MEAL, SLEEP, EXCRETION, GO-OUT, and REST. The
      proposed system installs pressure sensors to furniture and floors in home, and
      recognizes daily activities based on the object usage information. By using the
      proposed system, we can provide a warning sign for unhealthy cases such as
      skipping meals. And, the families who live in remote place can check that their
      parent takes a healthy daily living.

PMID- 19163887
TI  - Classification of continuously executed early morning activities using wearable
      wireless sensors.
AB  - In this paper, we study the personal monitoring system that classifies the
      continuously executed early morning activities of daily living. The system is
      intended to assist those with cognitive impairments due to traumatic brain
      injuries. The system can be used to help therapists in hospitals or could be
      deployed in one's home to track and monitor the activities executed by the
      recovering patients. We begin by briefly describing the infrastructure of our
      cost-effective system which uses fixed and wearable wireless sensors and show
      results related to the detection of activities continuously executed in the
      morning. Both frequency and time domain features from an accelerometer attached
      to the right wrist were extracted and used for classification using Gaussian
      mixture models, followed by a finite state machine. We show promising
      classification results obtained from 5 subjects. Overall classification rate is
      88.3 % for 4 activities of interests.

PMID- 19163888
TI  - Estimation of physical constraint condition by analyzing walking motions.
AB  - In this paper, the estimation system of physical constraint conditions is
      proposed using motion data during walks. Walking motions of subjects who are
      fixed braces on their bodies were measured by a motion capturing system. We
      focused on the acceleration data on the body and found which parts in the body
      are influenced by the physical constraint. The estimation of the physical
      constraint condition was done by Hidden Markov Model (HMM) based on the
      reliability map created from the recognition rate. Experimental result shows that
      we can efficiently estimate the constraint condition by using data of the
      particular body parts.

PMID- 19163889
TI  - Toward real time detection of the basic living activity in home using a wearable
      sensor and smart home sensors.
AB  - As the elderly people living alone are enormously increasing recently, we need
      the system inferring activities of daily living (ADL) for maintaining healthy
      life and recognizing emergency. The system should be constructed with sensors,
      which are used to associate with people's living while remaining as non intrusive
      views as possible. To do this, the proposed system use a triaxial accelerometer
      sensor and environment sensors indicating contact with subject in home.
      Particularly, in order to robustly infer ADLs, we present component ADL, which is
      decided with conjunction of human motion together, not just only contacted object
      identification. It is an important component in inferring ADL. In special,
      component ADL decision firstly refines misclassified initial activities, which
      improves the accuracy of recognizing ADL. Preliminary experiments results for
      proposed system provides overall recognition rate of over 97% over 8 component
      ADLs, which can be effectively applicable to recognize the final ADLs.

PMID- 19163890
TI  - Removal of ECG artifacts from EEG using a modified independent component analysis
      approach.
AB  - In this paper, we introduce a new automatic method for electrocardiogram (ECG)
      artifact elimination from the electroencephalogram (EEG) or the electrooculogram
      (EOG). It is based on a modification of the independent component analysis (ICA)
      algorithm which gives promising results while only using a single-channel EEG (or
      EOG) and the ECG. To check the effectiveness of our approach, we compared its
      correction rate with those obtained by ensemble average subtraction (EAS) and
      adaptive filtering (AF). For this purpose, we applied these algorithms to 10
      excerpts of polysomnographic sleep recordings containing ECG artifacts and other
      typical artifacts (e.g. movement, sweat, respiration, etc.). Two hundred
      successive interference peaks were examined in each excerpt to compute correction
      rates. We found that our modified ICA was the most robust to various waveforms of
      cardiac interference and to the presence of others artifacts, with a correction
      rate of 91.0%, against 83.5% for EAS and 83.1% for AF.

PMID- 19163891
TI  - A generalized subspace approach for estimating visual evoked potentials.
AB  - A "single-trial" signal subspace approach for extracting visual evoked potential
      (VEP) from the ongoing 'colored' electroencephalogram (EEG) noise is proposed.
      The algorithm applies the generalized eigendecomposition on the covariance
      matrices of the VEP and noise to transform them jointly into diagonal matrices in
      order to avoid a pre-whitening stage. The proposed generalized subspace approach
      (GSA) decomposes the corrupted VEP space into a signal subspace and noise
      subspace. Enhancement is achieved by removing the noise subspace and estimating
      the clean VEPs only from the signal subspace. The validity and effectiveness of
      the proposed GSA scheme in estimating the latencies of P100's (used in objective
      assessment of visual pathways) are evaluated using real data collected from
      Selayang Hospital in Kuala Lumpur. The performance of GSA is compared with the
      recently proposed single-trial technique called the Third Order Correlation
      (TOC).

PMID- 19163892
TI  - Comparison of unsupervised and supervised gene selection methods.
AB  - Modern machine learning methods based on matrix decomposition techniques like
      Independent Component Analysis (ICA) provide new and efficient analysis tools
      which are currently explored to analyze gene expression profiles. These
      exploratory feature extraction techniques yield informative expression modes
      (ICA) which are considered indicative of underlying regulatory processes. Their
      most strongly expressed genes represent marker genes for classification of the
      tissue samples under investigation. Comparison with supervised gene selection
      methods based on statistical scores or support vector machines corroborate these
      findings. The method is applied to macrophages loaded/de-loaded with chemically
      modified low density lipids.

PMID- 19163893
TI  - The selection of optimal ICA algorithm parameters for robust AEP component
      estimates using 3 popular ICA algorithms.
AB  - Many authors have used the Auditory Evoked Potential (AEP) recordings to evaluate
      the performance of their ICA algorithms and have demonstrated that this procedure
      can remove the typical EEG artifact in these recordings (i.e. blinking, muscle
      noise, line noise, etc.). However, there is little work in the literature about
      the optimal parameters, for each of those algorithms, for the estimation of the
      AEP components to reliably recover both the auditory response and the specific
      artifacts generated for the normal function of a Cochlear Implant (CI), used for
      the rehabilitation of deaf people. In this work we determine the optimal
      parameters of three ICA algorithms, each based on different independence
      criteria, and assess the resulting estimations of both the auditory response and
      CI artifact. We show that the algorithm utilizing temporal structure, such as
      TDSEP-ICA, is better in estimating the components of the auditory response, in
      recordings contaminated by CI artifacts, than higher order statistics based
      algorithms.

PMID- 19163894
TI  - Removal of ballistocardiogram artifact from EEG data acquired in the MRI scanner:
      selection of ICA components.
AB  - The removal of ballistocardiogram (BCG) artifact from the EEG recorded in the MRI
      scanner is challenging. Few studies have utilized independent component analysis
      (ICA) in this task. A drawback of ICA has been the proper selection of the BCG
      related components. The key idea in this work is to use the difference between
      the power spectrum of the artifact-processed data and the spectrum of data
      recorded outside the scanner as a cost function in the selection of the BCG
      related independent components. Forward floating selection algorithm was
      implemented to find the components to minimize this criterion. Also, the typical
      component selection criteria based on the correlation with electrocardiogram
      (ECG) signal and on explained variance were compared in this respect. The
      correlation criterion was least successful leaving considerable residual artifact
      in the signal. With the first few removed components the variance criterion
      performed as well as the minimum spectral difference criterion. With the variance
      criterion alone, however, the number of the components to be removed cannot be
      determined. The suggested methods may provide objective means to validate
      residual artifact or the possible loss of physiological signal due to artifact
      removal and to help selecting the proper artifact-related components.

PMID- 19163895
TI  - Electrocorticographic interictal spike removal via denoising source separation
      for improved neuroprosthesis control.
AB  - Electrocorticographic (ECoG) neuroprosthesis is a promising area of research that
      could provide channels of communication and control for patients who have lost
      their motor functions due to damage to the nervous system. However, implantation
      of subdural electrodes are clinically restricted to diagnostics of pre-surgical
      epileptic patients. Hence, interictal activity is present in the recordings
      across various areas of the sensorimotor cortex and suppresses the amplitude
      modulated features extracted to model hand trajectories. Denoising source
      separation is a recently introduced framework which extracts hidden structures of
      interest within the data through denoising the source estimates with filters
      designed around prior knowledge on the observations. Herein, we exploit the high
      amplitude quasiperiodic nature of the observed interictal spikes and show that
      removal of the interictal activity improves linear prediction of hand
      trajectories.

PMID- 19163896
TI  - Development of a Micro-Macro Neural Network to recognize rollover movement.
AB  - Bone metastasis patients suffer from pain when their trunks twist during
      movements such as rollovers. In this overall research project, our ultimate aim
      is to develop an effective rollover-support system for patients with cancer bone
      metastasis. The core of this system will be a pneumatic rubber muscle that will
      be operated based on the EMG signals from the patient's internal abdominal
      oblique muscle to limit the range of motion of the trunk twist only when the
      patients will feel the pain. The Time Delay Neural Network (TDNN) is the
      traditional method for recognizing the movement such as rollover using EMG
      signals. We have developed a new neural network, called the Micro-Macro Neural
      Network (MMNN), to recognize the rollover movement earlier and with more accuracy
      than possible with the TDNN. Recognition using MMNN was 49 (S.D. 45) (msec)
      faster than that using TDNN. The recognition rate before the rollover started was
      improved from 38% (TDNN) to 86% (MMNN). Additionally, the number of false
      recognitions using MMNN fell to only one third of those using TDNN. In addition,
      by using the unit contribution rate of the neural network, we found that the MMNN
      effectively accounted for the importance of past EMG data (the data gathered
      before the current measurement point). We also found that the de-noising
      performance of the MMNN was effective.

PMID- 19163897
TI  - Long short-term memory for apnea detection based on Heart Rate Variability.
AB  - The main drive force in apnea current diagnostic is to reduce overwhelming number
      of sleep disorders candidates by means of very simple-to-use, comfortable and
      cheap methodology. The proposed framework is based only on automatic analysis of
      electrocardiogram signal. The feature extraction stage was performed using
      methods of Heart Rate Variability and Detrended Fluctuation analysis. Feature
      spaces formed using these two methods were used as input to a Long Short-Term
      Memory Artificial Neural Network chosen for its capability to find temporally
      dependencies in the data. The framework was evaluated on Challenge 2000 Physionet
      database yielding successful rate 82.1%, sensitivity 85.5% and specificity 80.1%.

PMID- 19163898
TI  - Recognition of aggressive human behavior using binary local motion descriptors.
AB  - Video surveillance is an alternative approach to staff or self-reporting that has
      the potential to detect and monitor aggressive behaviors more accurately. In this
      paper, we propose an automatic algorithm capable of recognizing aggressive
      behaviors from video records using local binary motion descriptors. The proposed
      algorithm may increase the accuracy for retrieving aggressive behaviors from
      video records, and thereby facilitates scientific inquiry into this low frequency
      but high impact phenomenon that eludes other measurement approaches.

PMID- 19163899
TI  - Fuzzy structural algorithms to identify and characterize apnea and hypopnea
      episodes.
AB  - We present a new automated method to identify apneas and hypopneas and to relate
      them to the drops in blood oxyhemoglobin saturation that they produce. The
      algorithm takes advantage of the fuzzy set theory for the representation and
      manipulation of the vagueness of the medical knowledge on which it is based. Its
      structural nature allows us to easily modify the morphological detection
      criteria, and to perform a detailed characterization of the identified events.
      Based on this proposal, a tool for screening polysomnographic records has been
      developed. The tool allows the physician to modify the morphological criteria
      that define apneas, hypopneas, and desaturations as well as to inspect the
      descriptors that make up their characterization. Using this tool we have analyzed
      five polysomnographic recordings obtaining an overall correct detection rate of
      95%. The false negative rate was 6.6% and the false positive rate was 4.3%.

PMID- 19163900
TI  - Recognition of aging effect from cardiomechanical signals using novel SF-ART
      neural network.
AB  - In this study we applied Haar wavelets to extract essential features of cardiac
      mechanical signals classified them using a novel neural network so called,
      Supervised Fuzzy Adaptive Resonance Theory (SF-ART). Initial tests with sternal
      signals of cardiac vibration from six young, middle-aged and old subjects
      indicate that SF-ART can classify the subjects into three classes with a high
      accuracy, fast learning speed, and low computational load. The method is
      insensitive to latency and non-linear disturbance. Moreover, the applied wavelet
      transform requires no prior knowledge of the statistical distribution of data
      samples. This can offer a novel method for the analysis of the effects of aging
      on the heart and assessment of the physiological age of the heart.

PMID- 19163901
TI  - Context-aware mobile health monitoring: evaluation of different pattern
      recognition methods for classification of physical activity.
AB  - There are various applications of physical activity monitoring for medical
      purposes, such as therapeutic rehabilitation, fitness enhancement or the use of
      physical activity as context information for evaluation of other vital data.
      Physical activity can be estimated using acceleration sensor-systems fixed on a
      person's body. By means of pattern recognition methods, it is possible to
      identify with certain accuracy which movement is being performed. This work
      presents a comparison of different methods for recognition of daily-life
      activities, which will serve as basis for the development of an online activity
      monitoring system.

PMID- 19163902
TI  - An integrated biomedical telemetry system for sleep monitoring employing a
      portable body area network of sensors (SENSATION).
AB  - A flexible, scaleable and cost-effective medical telemetry system is described
      for monitoring sleep-related disorders in the home environment. The system was
      designed and built for real-time data acquisition and processing, allowing for
      additional use in intensive care unit scenarios where rapid medical response is
      required in case of emergency. It comprises a wearable body area network of
      Zigbee-compatible wireless sensors worn by the subject, a central database
      repository residing in the medical centre and thin client workstations located at
      the subject's home and in the clinician's office. The system supports
      heterogeneous setup configurations, involving a variety of data acquisition
      sensors to suit several medical applications. All telemetry data is securely
      transferred and stored in the central database under the clinicians' ownership
      and control.

PMID- 19163903
TI  - An effective method for component activity classification supporting location
      awareness and user identification.
AB  - We present an effective method for component activity classification supporting
      location awareness and user identification at the same time. The system is
      comprised of three modules: Pressure Sensing Module (PSM), Activity Detecting
      Module (ADM), and Receiving Station (RS). The ADM having a unique id is a
      wearable module putting on one's waist-belt, which classifies component activity
      such as sitting chair, lying bed, sitting sofa, etc. utilizing both user's
      interaction with household furniture and atomic activities like lie, sit, and
      stand. We limit transmission range of RF chip in PSM to around 1 m so that we can
      find the most adjacent furniture to the ADM. It makes possible to find the user's
      relative location to the PSM, so we can aware of both who and where the acting
      person is while recognizing his/her activities. We obtained 92.5% of average
      precision of the activity classification.

PMID- 19163904
TI  - Improving actigraph sleep/wake classification with cardio-respiratory signals.
AB  - Actigraphy for long-term sleep/wake monitoring fails to correctly classify
      situations where the subject displays low activity, but is awake. In this paper
      we propose a new algorithm which uses both accelerometer and cardio-respiratory
      signals to overcome this restriction. Acceleration, electrocardiogram and
      respiratory effort were measured with an integrated wearable recording system
      worn on the chest by three healthy male subjects during normal daily activities.
      For signal processing a Fast Fourier Transformation and as classifier a feed
      forward Artificial Neural Network was used. The best classifier achieved an
      accuracy of 96.14%, a sensitivity of 94.65% and a specificity of 98.19%. The
      algorithm is suitable for integration into a wearable device for long-term home
      monitoring.

PMID- 19163905
TI  - Optical fibre sensors embedded into technical textile for a continuous monitoring
      of patients under Magnetic Resonance Imaging.
AB  - The potential impact of optical fiber sensors embedded into medical textiles for
      the continuous monitoring of the patient during Magnetic Resonance Imaging (MRI)
      is presented. In that way, we report on several pure optical sensing technologies
      for pulse oximetry and respiratory movements monitoring. The technique for pulse
      oximetry measurement is known as NIRS (Near Infra-Red Spectroscopy) in a
      reflectance mode. On the other hand, we tested two different optical based
      designs for the respiratory motions measurements--a macro bending sensor and a
      Bragg grating sensor, designed to measure the elongation of thoracic and
      abdominal circumferences during breathing.

PMID- 19163906
TI  - Smart fabrics and interactive textile enabling wearable personal applications:
      R&D state of the art and future challenges.
AB  - Smart fabrics and interactive textiles (SFIT) are fibrous structures that are
      capable of sensing, actuating, generating/storing power and/or communicating.
      Research and development towards wearable textile-based personal systems allowing
      e.g. health monitoring, protection & safety, and healthy lifestyle gained strong
      interest during the last 10 years. Under the Information and Communication
      Programme of the European Commission, a cluster of R&D projects dealing with
      smart fabrics and interactive textile wearable systems regroup activities along
      two different and complementary approaches i.e. 'application pull' and
      'technology push'. This includes projects aiming at personal health management
      through integration, validation, and use of smart clothing and other networked
      mobile devices as well as projects targeting the full integration of
      sensors/actuators, energy sources, processing and communication within the
      clothes to enable personal applications such as protection/safety, emergency and
      healthcare. The integration part of the technologies into a real SFIT product is
      at present stage on the threshold of prototyping and testing. Several issues,
      technical as well user-centred, societal and business, remain to be solved. The
      paper presents on going major R&D activities, identifies gaps and discuss key
      challenges for the future.

PMID- 19163907
TI  - Wearable system-on-a-chip UWB radar for contact-less cardiopulmonary monitoring:
      present status.
AB  - The present status of the project aimed at the realization of an innovative
      wearable system-on-chip UWB radar for the cardiopulmonary monitoring is
      presented. The overall system consists of a wearable wireless interface including
      a fully integrated UWB radar for the detection of the heart beat and breath
      rates, and a IEEE 802.15.4 ZigBee low-power radio interface. The principle of
      operation of the UWB radar for the monitoring of the heart wall is summarized.
      With respect to the prior art, this paper reports the results of the experimental
      characterization of the intra-body channel loss, which has been carried out
      successfully in order to validate the theoretical model employed for the radar
      system analysis. Moreover, the main building blocks of the radar have been
      manufactured in 90 nm CMOS technology by ST-Microelectronics and the relevant
      performance are resulted in excellent agreement with those expected by post
      layout simulations.

PMID- 19163908
TI  - Non-invasive three-dimensional imaging of human diaphragm in-vivo.
AB  - Three-dimensional reconstruction of human diaphragm provide useful information on
      the functional anatomy of the respiratory system by the analysis of its geometry.
      The aim of the current work is the development of a new method for the 3D
      analysis of diaphragm geometry by the combination of free-hand Ultrasound (US)
      scans with an optoelectronic system of movement analysis for the tracking of the
      probe. 6 healthy subjects (age=24+/-2), have been measured with a free-hand US
      scanning of the abdomen in supine (SP) and seated position (ST), during breath
      holding at Functional Residual Capacity (FRC) and Total Lung Capacity (TLC). For
      one of them, measurements have been repeated in supine position in an MR scan for
      the validation of the method. Posture has different implications on diaphragm
      geometry depending on the respiratory volume. At FRC the ray of curvature (rho)
      in ST is 101.1+/-43.1 mm higher than in SP (p=0.006), while at TLC, posture
      influences the position of the diaphragm with a caudo-cranial displacement from
      SP to ST of 23.4+/-16.7mm (p=0.019). Diaphragm geometry at different lung volumes
      is influenced by the posture. In SP, rho increases of 105.9+/-48.3 mm (p=0.008)
      and there is a cranio-caudal displacement (Deltay) of 47.54+/-15 mm (p=0.002)
      shifting from FRC to TLC. In ST, Deltay=31.1+/-13.5 mm (p=0.006) while rho
      increases not significantly. Percentage errors between MR and US 3D
      reconstructions are 2.1% and 10.46% for Deltay and TLC/FRC rho ratio,
      respectively. US 3D reconstruction is a reliable method for the assessment of
      diaphragm functional anatomy. Posture directly influence diaphragm geometry and
      hence respiratory mechanics.

PMID- 19163909
TI  - Towards detecting surgical clips in 3D ultrasound for target localization in
      radiation therapy: a study on tissue phantoms.
AB  - A study is performed to measure the visibility of small surgical clips in 3D
      ultrasound volumes of a phantom as the first step towards using such clips as
      fiducial markers in radiation therapy. Visibility is calculated as the contrast
      to noise ratio of the echo from the clip to the background. The appearance of a
      resonance tail is also calculated using a moment analysis. Contrast is found to
      be high and mostly independent of material and size of the clip. All clips are
      visible, but the length of the tail is found to be dependent on clip orientation
      to the ultrasound beam. The consistent visibility of the clips suggests they are
      suitable as fiducial markers in ultrasound and the dependency of the resonance
      tail on orientation provides an opportunity to distinguish clips from other
      specular reflectors.

PMID- 19163910
TI  - A novel method to estimate the aortic pressure waveform using B-mode ultrasound
      images acquired from a suprasternal view.
AB  - A novel method to obtain the aortic pressure waveform using a sequence of B-mode
      images is developed in this project. An automatic edge detection algorithm is
      applied to a sequence of longitudinal images of the aortic arch acquired from a
      suprasternal view. The aortic distension waveform is obtained by measuring the
      distance between the two edges throughout the cardiac cycle. It is then
      calibrated using the systolic and diastolic pressures from the brachial artery to
      obtain an estimated pressure waveform. This method was applied to 5 healthy
      children, pulse pressure amplification and total arterial compliance were
      calculated from the estimated waveforms.

PMID- 19163911
TI  - A sensitive ultrasonic imaging method for targeted contrast microbubble
      detection.
AB  - We have recently developed a targeted imaging technique for selective and
      sensitive ultrasound molecular imaging by taking advantage of wideband transient
      high frequency acoustic emission from ultrasound contrast agents. The imaging
      modality makes use of a novel multi-frequency co-linear array (two outer 1.4 MHz
      and one center 5.3 MHz arrays) transducer integrated with the Siemens
      AntaresSystem. The imaging sequence includes a B-mode imaging pulse sequence in
      which a short pulse is transmitted with the outer low frequency arrays and
      received with the inner high frequency array (TLRH: transmit at low frequency and
      receive at high frequency), followed by a long radiation force pulse to induce
      immediate bubble adhesion using the center array, and a second B-mode imaging
      pulse sequence. The RF data obtained from the second B-mode pulse sequence are
      averaged and then subtracted from the first B-mode sequence. The imaging
      technique was tested in a targeted imaging phantom, where lipid-shelled biotin
      microbubbles flow within an avidin coated-cellulose. Results showed that tissue
      signals were suppressed up to 33 dB and a targeted bubble contrast-to-free bubble
      signal ratio of up to 23 dB was obtained from the composite sequence imaging.

PMID- 19163912
TI  - Development of an ultrasound system for measuring tissue strain of lymphedema.
AB  - This paper develops a portable measurement system for tissue strain distribution
      using ultrasonic pulse echo method. A single element ultrasonic transducer
      attached to a force sensor compresses biological tissue and observes the
      deformation process of the tissue. The center frequency of the ultrasound pulse
      is 3 MHz. The force applied to the tissue is kept at 10 N by an internal coil
      spring. Received echo signals are transferred to a personal computer via
      Universal Serial Bus. The developed measurement system was applied to measuring
      strain of subcutaneous fat for lymphedema patients and healthy subjects. The
      results quantified the fact that affected tissue becomes harder than unaffected
      tissue. Our experiment demonstrated that the system can be used for evaluating
      the condition of lymphedema with measurement of strain in subcutaneous tissue.

PMID- 19163913
TI  - Ultrasonic measurement of vascular scaffold elasticity using catheter system.
AB  - Characterization of grafted vascular scaffold is essential for evaluating its
      biocompatibility, maturity and structural intensity. Quantitative elastic modulus
      measurement of vascular scaffold powerfully assists its characterization because
      the mechanical property is closely related with the biocompatibility, maturity
      and structural intensity of the vascular scaffold. We have presented an in vitro
      or in vivo measurement system for the tissue-engineered vessel before and after
      grafting in the previous study, we present a novel and modified method for in
      vivo assessment and follow-up of the vascular scaffold in this study. The
      measured quantitative elastic modulus is converted into the regeneration score
      for in vivo assessment. The effectiveness of the proposed evaluation method was
      validated by in vivo experimental data using canines.

PMID- 19163914
TI  - Impact of compressed sensing of motor cortical activity on spike train decoding
      in Brain Machine Interfaces.
AB  - Decoding spike trains is an essential step to translate multiple single unit
      activity to useful control commands in cortically controlled Brain Machine
      Interface (BMI) systems. Extracting the spike trains of individual neurons from
      the recorded mixtures requires spike sorting, a computationally prohibitive step
      that precludes the development of fully implantable, small size and low power
      electronics. Previously, we reported on the ability to extract the critical
      information in these spike trains such as precise spike timing and firing rate of
      individual neurons using a compressed sensing strategy that overcomes the
      computational burden of the spike sorting step. Herein, we assess the decoding
      performance using this method and compare it to the case where classical spike
      sorting takes place prior to decoding. We use the local average of the sparsely
      represented data as discriminative features to 'informally' detect and classify
      spikes in the data stream. We demonstrate that there is a substantial gain in
      performance assessed under different decoding strategies, while much less
      computations are needed compared to spike sorting in the traditional sense.

PMID- 19163915
TI  - Decoding hand and cursor kinematics from magnetoencephalographic signals during
      tool use.
AB  - The ability to decode kinematics of intended movement from neural activity is
      essential for the development of prosthetic devices, such as artificial arms,
      that can aid motor-disabled persons. To date, most of the progress in the
      development of neuromotor prostheses has been obtained by decoding neural
      activity acquired through invasive means, such as microelectrode arrays seated
      into motor cortical tissue. In this study, we demonstrate the feasibility of
      decoding both hand position and velocity from non-invasive
      magnetoencephalographic signals during a center-out drawing task in familiar and
      novel environments. The mean correlation coefficients between measured and
      decoded kinematics ranged from 0.27-0.61 for the horizontal dimension of movement
      and 0.06-0.58 for the vertical dimension. Our results indicate that non-invasive
      neuroimaging signals may contain sufficient kinematic information for controlling
      neuromotor prostheses.

PMID- 19163916
TI  - Steady-state movement related potentials for brain computer interfacing.
AB  - An approach for brain computer interfacing (BCI) by analysis of the steady-state
      movement related potentials (ssMRP) is proposed in this paper. The neurological
      background of the ssMRPs which are primarily studied by means of the averaged
      electroencephalogram (EEG) signals are briefly reviewed. A simple feature
      extraction method is suggested for single trial ssMRP processing. The proposed
      BCI paradigm is tested by using the Fishers linear discriminant (FLD) classifier.
      The novelty of this approach is mainly in the application of rhythmic cues for
      BCI, simple recording setup, and straightforward computations which make the real
      time implementations plausible.

PMID- 19163917
TI  - Spectral modulation of LFP activity in M1 during dexterous finger movements.
AB  - Recent studies have shown that cortical local field potentials (LFP) contain
      information about planning or executing hand movement. While earlier research has
      looked at gross motor movements, we investigate the spectral modulation of LFP
      activity and its dependence on recording location during dexterous motor actions.
      In this study, we recorded LFP activity from the primary motor cortex of a
      primate as it performed a fine finger manipulation task involving different
      switches. The event-related spectral perturbations (ERSP) in four different
      frequency bands were considered for the analysis; 4 Hz, 6-15 Hz, 17-40 Hz and 75
      170 Hz. LFPs recorded from electrodes in the hand area showed the largest change
      in ERSP for the highest frequency band (75-170 Hz) (p 0.05), while LFPs recorded
      from electrodes placed more medially in the arm area showed the largest change in
      ERSP for the lowest frequency band (4 Hz) (p 0.05). Furthermore, the spectral
      information from the <4 Hz and 75-150 Hz frequency bands was used to successfully
      decode the three dexterous grasp movements with an average accuracy of up to 81%.
      Although previous research has shown that multi-unit neuronal activity can be
      used to decode fine motor movements, these results demonstrate that LFP activity
      can also be used to decode dexterous motor tasks. This has implications for
      future neuroprosthetic devices due to the robustness of LFP signals for chronic
      recording.

PMID- 19163918
TI  - Three cases of feature correlation in an electrocorticographic BCI.
AB  - Three human subjects participated in a closed-loop brain computer interface
      cursor control experiment mediated by implanted subdural electrocorticographic
      arrays. The paradigm consisted of several stages: baseline recording, hand and
      tongue motor tasks as the basis for feature selection, two closed-loop one
      dimensional feedback experiments with each of these features, and a two
      dimensional feedback experiment using both of the features simultaneously. The
      two selected features were simple channel and frequency band combinations
      associated with change during hand and tongue movement. Inter-feature correlation
      and cross-correlation between features during different epochs of each task were
      quantified for each stage of the experiment. Our anecdotal, three subject, result
      suggests that while high correlation between horizontal and vertical control
      signal can initially preclude successful two-dimensional cursor control, a
      feedback-based learning strategy can be successfully employed by the subject to
      overcome this limitation and progressively decorrelate these control signals.

PMID- 19163919
TI  - RatCar system for estimating locomotion states using neural signals with
      parameter monitoring: Vehicle-formed brain-machine interfaces for rat.
AB  - An online brain-machine interface (BMI) in the form of a small vehicle, the
      'RatCar,' has been developed. A rat had neural electrodes implanted in its
      primary motor cortex and basal ganglia regions to continuously record neural
      signals. Then, a linear state space model represents a correlation between the
      recorded neural signals and locomotion states (i.e., moving velocity and
      azimuthal variances) of the rat. The model parameters were set so as to minimize
      estimation errors, and the locomotion states were estimated from neural firing
      rates using a Kalman filter algorithm. The results showed a small oscillation to
      achieve smooth control of the vehicle in spite of fluctuating firing rates with
      noises applied to the model. Major variation of the model variables converged in
      a first 30 seconds of the experiments and lasted for the entire one hour session.

PMID- 19163920
TI  - Wireless medical ultrasound video transmission through noisy channels.
AB  - Recent advances in video compression such as the current state-of-the-art
      H.264/AVC standard in conjunction with increasingly available bitrate through new
      technologies like 3G, and WiMax have brought mobile health (m-Health) healthcare
      systems and services closer to reality. Despite this momentum towards m-Health
      systems and especially e-Emergency systems, wireless channels remain error prone,
      while the absence of objective quality metrics limits the ability of providing
      medical video of adequate diagnostic quality at a required bitrate. In this paper
      we investigate different encoding schemes and loss rates in medical ultrasound
      video transmission and come to conclusions involving efficiency, the trade-off
      between bitrate and quality, while we highlight the relationship linking video
      quality and the error ratio of corrupted P and B frames. More specifically, we
      investigate IPPP, IBPBP and IBBPBBP coding structures under packet loss rates of
      2%, 5%, 8% and 10% and derive that the latter attains higher SNR ratings in all
      tested cases. A preliminary clinical evaluation shows that for SNR ratings higher
      than 30 db, video diagnostic quality may be adequate, while above 30.5 db the
      diagnostic information available in the reconstructed ultrasound video is close
      to that of the original.

PMID- 19163921
TI  - Development of a cell phone-based video streaming system for persons with early
      stage Alzheimer's disease.
AB  - The current paper presents details regarding the early developments of a memory
      prompt solution for persons with early dementia. Using everyday technology, in
      the form of a cell-phone, video reminders are delivered to assist with daily
      activities. The proposed CPVS system will permit carers to record and schedule
      video reminders remotely using a standard personal computer and web cam. It is
      the aim of the three year project that through the frequent delivery of helpful
      video reminders that a 'virtual carer' will be present with the person with
      dementia at all times. The first prototype of the system has been fully
      implemented with the first field trial scheduled to take place in May 2008.
      Initially, only three patient carer dyads will be involved, however, the second
      field trial aims to involve 30 dyads in the study. Details of the first prototype
      and the methods of evaluation are presented herein.

PMID- 19163922
TI  - Electronic data capture platform for clinical research based on mobile phones and
      near field communication technology.
AB  - Electronic data capture systems support data acquisition for clinical research
      and enable the evaluation of new investigational medical devices. In case of
      evaluating a device the most challenging part is the user interface i.e. the
      solution how to acquire the data within a clinical setting and to synchronize
      them with a web-based data centre. The aim of this paper is to describe the
      development of an electronic data capture system with a mobile data input
      solution based on mobile phones and Near Field Communication technology. This
      system was evaluated within a real clinical setting and demonstrated high
      usability, security and reliability.

PMID- 19163923
TI  - A mobile-phone based teledermatology system to support self-management of
      patients suffering from psoriasis.
AB  - Psoriasis is one of the most common chronic skin diseases, affecting about 2% of
      the population world wide. Continuous clinical monitoring with periodic
      assessment of the state of the disease is essential for long-term therapy
      optimization. We present a mobile phone based telemedical compliance management
      system for psoriasis-patients. Using special software, patients can acquire
      health parameters such as their body weight, take photos of their psoriasis
      lesions, and report adverse effects. The data are automatically sent to a
      monitoring centre, where they are provided to the patient's physician via the use
      of a web-browser. In case of therapy relevant events, email or SMS notifications
      can be sent to the physician. If necessary, the physician can send feedback
      messages to the patient, e.g. for admitting the patient to the clinic for further
      examinations. The system has been implemented and functional tests have proven
      its functionality. Currently, the system is used in the course of a medical case
      series.

PMID- 19163924
TI  - New functions developed for ICU/CCU remote monitoring system using a 3G mobile
      phone and evaluations of the system.
AB  - As a combination of medical information and Telecommunication technologies,
      telemedicine plays a more and more important role in supporting doctors to
      diagnose and taking care of people's daily health. It is also an appropriate
      means to solve the conflict between aging of population and inadequacy of
      doctors, which are the actual condition and inevitable developing trend of the
      society not only in developed countries. In this paper, some new functions are
      developed for a ICU/CCU Remote Monitoring System using a 3G mobile phone.
      Furthermore, some evaluations of the system have been implied on several
      different mobile phones. The system is anticipated to be adopted by hospitals for
      its accuracy and real-time performance to supporting telediagnosis for patients
      in ICU/CCU.

PMID- 19163925
TI  - Subjective and objective quality assessment in wireless teleultrasonography
      imaging.
AB  - Mobile Robotic teleultrasonography is an emerging technology that can be applied
      in different clinical settings for remote ultrasound scanning without the need of
      the expert at the point of care. Guaranteed medical image quality for diagnostic
      purposes and their delivery in bandwidth limited wireless environments is a
      challenging issue. In this paper we present some of the subjective and objective
      image analysis acquired from a robotic teleultrasonography system operated
      remotely by the expert to provide an assessment of these medical imaging measures
      for such advanced wireless telemedical system.

PMID- 19163926
TI  - Reflex modulation is linked to the orientation of arm mechanics relative to the
      environment.
AB  - To successfully complete a motor task, it is necessary to control not only the
      kinematics and dynamics of a limb, but also its mechanical properties. In a
      multijoint task such as the control of arm posture, limb mechanics are
      directional, resisting external disturbances more effectively in certain
      directions than others. It has been demonstrated that feedforward neuromotor
      pathways can regulate these directional characteristics of the arm to compensate
      for changes in the mechanical properties of the environment. However, it is
      unclear if spinal reflex pathways exhibit a similar specificity. The present
      results suggest that the sensitivity of the human stretch reflex also can be
      tuned to adapt the mechanical properties of the arm in a task appropriate manner.
      We hypothesized that the orientation of arm mechanics relative to the mechanical
      properties of the environment would influence reflex adaptation. Two
      destabilizing environments, oriented relative to the mechanical properties of the
      arm, were used to test this hypothesis. These environments were simulated using a
      3 degrees of freedom (DOF) robot, which also was used to perturb arm posture. The
      resulting reflexes, assessed by electromyograms recorded from 8 muscles, were
      found to modulate in accordance with how the environmental instability was
      oriented relative to the mechanical properties of the arm. Our results suggest
      that stretch sensitive reflexes throughout the arm are modulated in a coordinated
      manner corresponding to the orientation of arm mechanics relative to the
      environment.

PMID- 19163927
TI  - Impedance control complements incomplete internal models under complex external
      dynamics.
AB  - In this paper, we investigate motor adaptation of human arm movements to external
      dynamics. In an experiment, we tried to determine whether humans can learn an
      internal model of a mixed force field (V+P) that was the sum of a velocity
      dependent force field (V) and a position-dependent force field (P). The
      experimental results show that the subjects did not learn the internal model of
      V+P accurately and they compensated for the loads by using impedance control. Our
      results suggest that humans use impedance control when internal models become
      inaccurate because of the complexity of the external dynamics.

PMID- 19163928
TI  - Impedance control is tuned to multiple directions of movement.
AB  - Humans are able to learn tool-handling tasks, such as carving, demonstrating
      their competency to make and vary the direction of movements in unstable
      environments. It has been shown that when a single reaching movement is repeated
      in unstable dynamics, the central nervous system (CNS) learns an impedance
      internal model to compensate for the environment instability. However, there is
      still no explanation for how humans can learn to move in various directions in
      such environments. In this study, we investigated whether and how humans
      compensate for instability while learning two different reaching movements
      simultaneously. Results show that when performing movements in two different
      directions, separated by a 35 degrees angle, the CNS was able to compensate for
      the unstable dynamics. After adaptation, the force was found to be similar to the
      free movement condition, but stiffness increased in the direction of instability,
      specifically for each direction of movement. Our findings suggest that the CNS
      either learned an internal model generalizing over different movements, or
      alternatively that it was able to switch between specific models acquired
      simultaneously.

PMID- 19163929
TI  - Exploring the human grip force system: a preliminary study.
AB  - It has been postulated that cutaneo-receptors from the digits contribute to the
      control of manipulatory functions of the hand. However, few studies have examined
      the dynamics of the human grip force system (HGFS) in terms of the dynamic
      relationship between the vertical loads, taken as an input and the resulting grip
      force, taken as the output. This paper describes the experimental procedures we
      have developed to explore the HGFS and presents some initial experimental
      results. These demonstrate that the step response of the HGFS is biphasic. The
      first, short latency phase, likely involves only passive and intrinsic
      components. The second, longer latency phase is likely related to reflex
      mechanisms since it is preceded by a strong burst of EMG. Moreover, the HGFS
      response depended nonlinearly on the amplitude and direction of the load applied.
      These results indicate that further investigation of HGFS dynamics will require
      the use of nonlinear identification methods.

PMID- 19163930
TI  - Synergies during reach-to-grasp: a comparative study between healthy and C6-C7
      quadriplegic subjects.
AB  - Analysis of functional capacities modifications after spinal cord injuries may
      have an interest in clinical rehabilitation programs. In this framework, this
      study is focused on the analysis of motor synergies i.e. how the upper-limb
      degrees of freedom (DOFS) are organized when considering C6-C7 quadriplegic
      subjects performing a reaching task. A previous work has shown that sharing
      patterns between DOFS are preserved. Using the uncontrolled manifold hypothesis
      (UCM), we investigate the second aspect of motor synergies i.e. how performance
      is allowed to show both stability against perturbations and flexibility to solve
      concurrent tasks. This procedure allows to evaluate the stabilization of a
      specific and selective performance variable through the variability of joint
      angles. In the present study, the wrist 3D path was considered and the
      variability of its trajectory is decomposed into two parts: one which does not
      affect the value of this performance variable (goal equivalent variance or GEV)
      and one which does (non goal equivalent variance or NGEV). Results showed that
      quadriplegic subjects present the same variance decomposition than healthy
      subjects suggesting that, despite the motor deficiency, flexibility is still
      allowed during movement execution.

PMID- 19163931
TI  - Muscle synergies during walking: comparison between young and elderly people.
      Preliminary results.
AB  - The present work was aimed at analysing the young and elderly people muscular
      activation in order to provide evidences regarding the different role of the
      muscular groups in locomotion. The tested hypothesis concerns the different
      strategy of the counterparts, that is a greater effort in preserving stability
      and safety in elders versus a greater importance in the propulsion in young. Five
      young and five elderly subjects were involved in the experiments and were asked
      to walk with 6 cadences, from 40 to 140 step/min. Muscle activations of twelve
      muscles were recorded, filtered, time-interpolated in 200 points over a gait
      cycle, averaged on the steps and processed by using Factor Analysis. Results
      showed that young and elderly muscle activations were described by factors
      behaving in opposite manner between the groups. The authors hypothesized that
      ageing may involve modifications in the peripheral areas of the Central Nervous
      System, producing neuromuscular adaptation.

PMID- 19163932
TI  - Global registration of multiple bone fragments using statistical atlas models:
      feasibility experiments.
AB  - We propose a new technique to automatically register multiple bone fragments of a
      fracture using a global registration method guided by a statistical anatomical
      atlas model. The atlas is created by using the principal component analysis of
      three-dimensional meshes generated from the Computed Tomography (CT) data of five
      left femur bone cadavers. The fracture fragments are initially aligned to the
      generated atlas by using a local point descriptor which can robustly identify a
      set of potential corresponding points among fragments and the mean atlas model. A
      global registration algorithm is then utilized to fine-tune the alignment among
      the fractures and the mean atlas model. Performed experimental simulations on the
      human femur bone cadavers verify the feasibility of the proposed registration
      algorithm.

PMID- 19163933
TI  - Simultaneous registration and intensity normalization of SPECT perfusion images.
AB  - The analysis of 3D SPECT brain images requires several pre-processing steps such
      as registration, intensity normalization and brain extraction. Usually,
      registration is performed before intensity normalization, which requires robust
      registration methods, such as those based on the maximization of the Mutual
      Information (MI), which are computationally complex. In this paper we propose
      using a computationally simple method to perform the simultaneous registration
      and intensity normalization of SPECT brain perfusion images. The approach, which
      extends to 3D data a method originally proposed in [1] for 2D photographic
      images, estimates in alternate steps the intensity normalization parameters and
      the registration parameters. Our experiments, with real SPECT images, show that
      the proposed registration method leads to results similar to those obtained by
      using more expensive algorithms such as those based on the MI criterion.

PMID- 19163934
TI  - Real-time intensity-based rigid 2d-3d medical image registration using RapidMind
      Multi-core Development Platform.
AB  - In this paper, we present an efficient intensity-based rigid 2D-3D image
      registration method. We implement the algorithm using the RapidMind Multi-core
      Development Platform(1) to exploit the highly parallel multi-core architecture of
      graphics processing units (GPUs). We use a ray casting algorithm to generate the
      digitally reconstructed radiographs (DRRs) on GPUs and efficiently reduce the
      complexity of DRR construction. The registration optimization problem is solved
      by the Gauss-Newton method. To fully exploit the multi-core parallelism, we
      implement almost the entire registration process in parallel by RapidMind. We
      also discuss the RapidMind implementation of the major computation steps.
      Numerical results are presented to demonstrate the efficiency of our method.

PMID- 19163935
TI  - Effective 2D-3D medical image registration using Support Vector Machine.
AB  - Registration of pre-operative 3D volume dataset and intra-operative 2D images
      gradually becomes an important technique to assist radiologists in diagnosing
      complicated diseases easily and quickly. In this paper, we proposed a novel 2D/3D
      registration framework based on Support Vector Machine (SVM) to compensate the
      disadvantages of generating large number of DRR images in the stage of intra
      operation. Estimated similarity metric distribution could be built up from the
      relationship between parameters of transform and prior sparse target metric
      values by means of SVR method. Based on which, global optimal parameters of
      transform are finally searched out by an optimizer in order to guide 3D volume
      dataset to match intra-operative 2D image. Experiments reveal that our proposed
      registration method improved performance compared to conventional registration
      method and also provided a precise registration result efficiently.

PMID- 19163936
TI  - Fast feature based multi slice to volume registration using phase congruency.
AB  - Slice to volume registration is very useful in many medical imaging applications,
      for example, fusing static high resolution three dimensional (3D) image volumes
      to dynamic two dimensional (2D) slice data for deriving motion information in 3D.
      Though information theoretic registration methods such as Mutual Information are
      usually robust, they are time intensive and typically require a high level of
      field-of-view correspondence between the source and target images. In single
      slice to volume registration scenarios, where such correspondence is limited,
      registration accuracy and robustness often deteriorate. In this paper, we present
      a novel registration method that maintains robustness and accuracy while
      significantly increasing registration speed. Our approach employs multiple slice
      (as opposed to single slice) to volume registration, which increases the amount
      of potential matching information while maintaining a small number of slices and
      hence facilitates the often necessary high speed dynamic image acquisition. Our
      proposed registration approach first extracts phase congruency information from
      the slices/volume using oriented 2D Gabor wavelets. Using local non maximum
      suppression, we then automatically obtain a robust and accurate set of feature
      points that are subsequently matched using an Iterative Closest Point (ICP)
      approach. Validation on BrainWeb simulated magnetic resonance imaging (MRI) data
      showed significant gains in speed ( approximately 40-fold increase) when compared
      to conventional Mutual Information based volumetric registration while
      maintaining comparable robustness and accuracy levels.

PMID- 19163937
TI  - 3D-3D tubular organs registration based on bifurcations for the CT images.
AB  - The registration of tubular organs (pulmonary tracheobronchial tree or
      vasculature) of 3D medical images is critical in various clinical applications
      such as surgical planning and radiotherapy. In this paper, we present a novel
      method for tubular organs registration based on the automatically detected
      bifurcation points of the tubular organs. We first perform a 3D tubular organ
      segmentation method to extract the centerlines of tubular organs and radius
      estimation in both planning and respiration-correlated CT (RCCT) images. This
      segmentation method automatically detects the bifurcation points by applying
      Adaboost algorithm with specially designed filters. We then apply a rigid
      registration method which minimizes the least square error of the corresponding
      bifurcation points between the planning CT images and the respiration-correlated
      CT images. Our method has over 96% success rate for detecting bifurcation
      points.We present very promising results of our method applied to the
      registration of the planning and respiration-correlated CT images. On average,
      the mean distance and the root-mean-square error (RMSE) of the corresponding
      bifurcation points between the respiration-correlated images and the registered
      planning images are less than 2.7 mm.

PMID- 19163938
TI  - Periodic breathing and state instability during supine laboratory recordings in
      chronic heart failure patients.
AB  - This study was conceived to analyze EEG state transitions and their relationship
      with ventilatory oscillations during daytime supine periodic breathing (PB) in
      heart failure patients. To this purpose, a semi-automated, frequency-based
      methodology was developed, and testing was carried out in 5 patients with PB. We
      found that apneas and hypopneas very often (86% on average) begin in synchrony
      with transitions from wakefulness to theta activity, and end in synchrony with
      the opposite transition. These results suggest that in these patients chemical
      instability secondary to the impaired hemodynamics coexists and interacts with
      state instability.

PMID- 19163939
TI  - Abdominal fetal ECG enhancement by event synchronous canceller.
AB  - Abdominal signals (ADS) recorded from pregnant women represent an important tool
      for monitoring the fetal heart rate (FHR) variability and the well-being state of
      the fetus, mainly because it has the advantage of being noninvasive. Thus, no
      risk is given during recording either for the mother or for the fetus, but
      complex signal processing steps are necessary, mainly due to the presence of the
      maternal ECG in the ADS, in order to achieve a clean fetal electrocardiogram
      (fECG). The paper presents an improved application of the Event Synchronous
      Canceller (ESC) for maternal electrocardiogram (mECG) suppression. An adaptive
      mECG template which also includes the P and T waves is considered for the ESC
      algorithm. ESC is able to perfectly separate the mECG even though the fetal beats
      overlap with the maternal QRS complex (mQRS). The algorithm is applied both on
      real ADS recorded during pregnancy and on simulated ADS data; the latter now uses
      simulation of all signal and noise components, including the fetal and maternal
      ECG. The modified ESC shows good results in extracting a cleaned fECG signal that
      can help in reducing the inconsistency in interpretation of FHR. Thus the false
      positive diagnosis regarding the health status of fetus is strongly reduced.

PMID- 19163940
TI  - Fully digital pacemaker detection in ECG signals using a non-linear filtering
      approach.
AB  - This paper deals with the detection of pacemaker pulses in an electrocardiogram
      (ECG) waveform. In order to realize a pulse detector that is robust to a wide
      band electromyographic (EMG) noise, we propose a (patent pending) fully digital
      approach that exploits a two step filtering strategy, followed by a threshold
      comparison. By resorting to computer simulations which employ a synthetic and
      realistic ECG signal model, we show that our approach is particularly effective
      and it significantly outperforms a well known patented algorithm.

PMID- 19163941
TI  - Nonlinear regression for sub-peak detection of intracranial pressure signals.
AB  - The management of many neurological disorders such as traumatic brain injuries
      relies on the continuous measurement of intracranial pressure (ICP). Following
      recent studies, the automatic analysis of ICP pulse seems to be a promising tool
      for forecasting intracranial and cerebrovascular pathophysiological changes.
      MOCAIP algorithm has recently been developed to automatically extract ICP
      morphological features in real time. The algorithm is capable of enhancing ICP
      signal quality, recognizing legitimate ICP pulses, and designating the three
      peaks in an ICP pulse. This paper extends MOCAIP by using a regression model
      instead of Gaussian priors during the peak designation to improve the accuracy of
      the process. The experimental evaluations of the proposed algorithm are performed
      on a ICP signal database built from 700 hours of recordings from 66 neurosurgical
      patients. They indicate that the use of a regression model significantly
      increases the peak designation accuracy.

PMID- 19163942
TI  - A two-pulse technique for extracting 3rd harmonic from ultrasound contrast agent
      echo signal.
AB  - Multi-pulse techniques like CPS (contrast pulse sequence) and TPS (triplet pulse
      sequence) are the most popular methods for separating the 3rd harmonic signals
      from received signal. Those two methods, however, transmit a pulse at least three
      times along each scanline with different phase and amplitude, which results in
      the frame rate reduction. In this paper, we propose a technique using two pulses
      whose phase difference is 90 degrees and a simple digital filter. The second
      harmonic signal is eliminated by summing two received signals as their phase
      difference becomes 180 degrees and then the fundamental signals are eliminated by
      using a digital filter. Computer simulations are performed for different values
      of signal bandwidths and filter specifications. The results show the maximum
      error is -35.5 dB compared to TPS.

PMID- 19163943
TI  - Automatic registration of retina images based on genetic techniques.
AB  - The aim of this paper is to develop an automatic method for the registration of
      multitemporal digital images of the fundus of the human retina. The images are
      acquired from the same patient at different times by a color fundus camera. The
      proposed approach is based on the application of global optimization techniques
      to previously extracted maps of curvilinear structures in the images to be
      registered (such structures being represented by the vessels in the human
      retina): in particular, a genetic algorithm is used, in order to estimate the
      optimum transformation between the input and the base image. The algorithm is
      tested on two different types of data, gray scale and color images, and for both
      types, images with small changes and with large changes are used. The comparison
      between the registered images using the implemented method and a manual one
      points out that the proposed algorithm provides an accurate registration. The
      convergence to a solution is not possible only when dealing with images taken
      from very different view-points.

PMID- 19163944
TI  - Automatic detection of red lesions in retinal images using a multilayer
      perceptron neural network.
AB  - Diabetic Retinopathy (DR) is an important cause of visual impairment among people
      of working age in industrialized countries. Automatic detection of DR clinical
      signs in retinal images would be an important contribution to the diagnosis and
      screening of the disease. The aim of the present study is to automatically detect
      some of these clinical signs: red lesions (RLs), like hemorrhages (HEs) and
      microaneurysms (MAs). Based on their properties, we extracted a set of features
      from image regions and selected the subset which best discriminated between these
      RLs and the retinal background. A multilayer perceptron (MLP) classifier was
      subsequently used to obtain the final segmentation of RLs. Our database was
      composed of 100 images with variable color, brightness, and quality. 50 of them
      were used to obtain the examples to train the MLP classifier. The remaining 50
      images were used to test the performance of the method. Using a lesion based
      criterion, we reached a mean sensitivity of 86.1% and a mean positive predictive
      value of 71.4%. With an image-based criterion, we achieved a 100% mean
      sensitivity, 60.0% mean specificity and 80.0% mean accuracy.

PMID- 19163945
TI  - Improvement of automated detection method of hemorrhages in fundus images.
AB  - This paper describes an improved method for detecting hemorrhages in fundus
      images. The detection of hemorrhages is one of the important factors in the early
      diagnosis of diabetic retinopathy. So, we had suggested several methods for
      detecting abnormalities in fundus images, but our methods had some problems. We
      propose a new method for preprocessing and false positive elimination in the
      present study. The brightness of the fundus image was changed by the nonlinear
      curve with brightness values of the hue saturation value (HSV) space. In order to
      emphasize brown regions, gamma correction was performed on each red, green, and
      blue-bit image. Subsequently, the histograms of each red, blue, and blue-bit
      image were extended. After that, the hemorrhage candidates were detected using
      density analysis. Finally, false positives were removed by using rule-based
      method and 3 Mahalanobis distance classifiers with a 45-feature analysis. To
      evaluate the new method for the detection of hemorrhages, we examined 125 fundus
      images, including 35 images with hemorrhages and 90 normal images. The
      sensitivity and specificity for the detection of abnormal cases were 80% and 80%,
      respectively.

PMID- 19163946
TI  - Retina lesion and microaneurysm segmentation using morphological reconstruction
      methods with ground-truth data.
AB  - In this work we report on a method for lesion segmentation based on the
      morphological reconstruction methods of Sbeh et. al. We adapt the method to
      include segmentation of dark lesions with a given vasculature segmentation. The
      segmentation is performed at a variety of scales determined using ground-truth
      data. Since the method tends to over-segment imagery, ground-truth data was used
      to create post-processing filters to separate nuisance blobs from true lesions. A
      sensitivity and specificity of 90% of classification of blobs into nuisance and
      actual lesion was achieved on two data sets of 86 images and 1296 images.

PMID- 19163947
TI  - Contextual detection of diabetic pathology in wide-field retinal angiograms.
AB  - We report a novel algorithm to locate vascular leakage and ischemia in retinal
      angiographic image sequences leveraging contextual knowledge of co-occurring
      pathologies. The key contributions are the use of spatio-temporal features
      exploiting the evolution of intensity levels over the sequence and contextual
      knowledge to detect ischemia. The specific nature of these diseased regions is
      determined using an AdaBoost learning algorithm. Training was performed with a
      varied set of 16 ground-truth image sequences, and testing on unseen images. The
      images used were acquired with an Optos ultrawide-field scanning laser
      ophthalmoscope. Evaluation against manual annotations demonstrates successful
      location of 93% of leakage regions and 70% of ischemic regions.

PMID- 19163948
TI  - Using a patient image archive to diagnose retinopathy.
AB  - Diabetes has become an epidemic that is expected to impact 365 million people
      worldwide by 2025. Consequently, diabetic retinopathy is the leading cause of
      blindness in the industrialized world today. If detected early, treatments can
      preserve vision and significantly reduce debilitating blindness. Through this
      research we are developing and testing a method for automating the diagnosis of
      retinopathy in a screening environment using a patient archive and digital fundus
      imagery. We present an overview of our content-based image retrieval (CBIR)
      approach and provide performance results for a dataset of 98 images from a study
      in Canada when compared to an archive of 1,355 patients from a study in the
      Netherlands. An aggregate performance of 89% correct diagnosis is achieved,
      demonstrating the potential of automated, web-based diagnosis for a broad range
      of imagery collected under different conditions and with different cameras.

PMID- 19163949
TI  - Computational study of an augmented minimal model for glycaemia control.
AB  - In this paper we introduce a new model structure for the metabolic effects of
      intravenous insulin on blood glucose in man and derive its parameter values from
      the widely used model of Sorensen. The proposed model attempts to combine the
      advantages of the existing comprehensive and minimal models. Validation of the
      new model is done through deriving equivalent nonparametric nonlinear models in
      the form of Principal Dynamic Modes. We show that the new structure can represent
      the insulin-glucose dynamics of healthy subjects as well as Type 1 and Type 2
      diabetics, with appropriate adjustment in its parameters.

PMID- 19163950
TI  - A software framework for multiscale and multilevel physiological model
      integration and simulation.
AB  - Emergence of systems biology motivated more comprehensive and integrative
      approaches for modeling physiological processes. In this paper, the design of a
      software framework for facilitating the integration of multilevel and multiscale
      physiological processes is presented. To build such an integrative environment, a
      layered design is proposed, where the structural and functional information is
      separated from the information flow and integration mechanism. Interfacing
      mechanisms are proposed to handle the integration of multilevel and multiscale
      processes. Integration of the processes and the information flow among the
      processes is modularized to use the anatomical and physiological information. The
      aim of the proposed design is to enhance the model development processes; but
      more importantly to accelerate the development, analysis and testing of
      integration approaches for multiscale and multilevel physiological models.

PMID- 19163951
TI  - Physiologically based pharmacokinetic model of midazolam disposition during
      pregnancy.
AB  - Disposition of drugs in pregnant women is poorly understood in spite of
      widespread prescription of drugs to women during gestation. We have developed a
      whole body physiologically based pharmacokinetic (PBPK) model to explore the
      effects of pregnancy on pharmacokinetics. The model accounts for maternofetal
      changes over the course of gestation; physiological and drug-specific parameters
      are taken from literature. Here we preliminarily demonstrate the model's utility
      to predict midazolam pharmacokinetics following intravenous bolus dosing in women
      undergoing Caesarian section. Simulations of maternal venous plasma
      concentrations compare favorably with data extracted from historical studies.

PMID- 19163952
TI  - An agent-based stochastic tumor model for predicting mitotic arrest drug
      response.
AB  - We present a 2D agent-based stochastic solid tumor model which incorporates
      cellular response to a chemotherapeutic drug such as paclitaxel (Taxol). First,
      we show that our model not only reproduces the findings of past mathematical
      models but also agrees qualitatively with previously observed experimental
      findings in vitro. Then, the model is used to study two contrasting methods of
      chemotherapeutic dosing: (1) maximum tolerated dose (MTD) and (2) metronomic
      dosing. Results of our simulations confirm the typical clinical observation that
      a single front-loaded dosing to MTD leads to a period of remission followed by
      recurrence, while metronomic dosing maintains or reduces the tumor size. These
      results suggest patient treatment strategies should favor the more recently
      proposed metronomic dosing paradigm over the traditionally used MTD therapy. The
      model proposed here is adaptable to different solid tumor types as well as
      different chemotherapeutic drug pharmacokinetic and pharmacodynamic properties,
      making it ideal for similar studies on different clinical problems.

PMID- 19163953
TI  - Mechanistic simulations explain paradoxical saquinavir metabolism during in vitro
      vectorial transport study.
AB  - We were confronted by an unexpected observation: in a Transwell study of
      confluent, Cyp3A4 and P-gp-expressing Caco-2 cells, higher intracellular
      saquinavir levels, yet less first metabolite (M7) formation were observed
      following apical dosing, compared to basal dosing. To test two seemingly
      plausible hypothesized explanations, we constructed an in silico working analogue
      using the synthetic method. Neither mechanism alone was sufficient, but when
      combined and tuned within the analogue, the results generated were a semi
      quantitative match to the experimental data. After 60 cycles, more of the
      simulated dose was present within analogue cells as parent drug after apical
      dosing. Furthermore, less M7 was present after apical dose. The paradox
      disappeared by having simulated drugs equilibrate among separate intracellular
      zones. Building, studying, and exploring mechanistic explanations for complex wet
      lab phenomena using the new methods improved insight into the referent system,
      while providing a straightforward, scientific means of testing the plausibility
      of mechanistic hypotheses.

PMID- 19163954
TI  - Model Predictive Control of blood glucose in Type 1 diabetes: the Principal
      Dynamic Modes approach.
AB  - This computational study demonstrates the efficacy of regulating blood glucose in
      Type 1 diabetics with a Model Predictive Control strategy, utilizing a
      nonparametric / Principal Dynamic Modes model. For this purpose, a stochastic
      glucose disturbance signal is introduced and a simple methodology for predicting
      its future values is developed. The results of our simulations confirm that the
      proposed algorithm achieves very good performance, is computationally efficient
      and avoids hypoglycaemic events.

PMID- 19163956
TI  - Automated patient-specific classification of premature ventricular contractions.
AB  - In this paper, we present an automated patient-specific electrocardiogram (ECG)
      beat classifier designed for accurate detection of premature ventricular
      contractions (PVCs). In the proposed feature extraction scheme, the principal
      component analysis (PCA) is applied to the dyadic wavelet transform (DWT) of the
      ECG signal to extract morphological ECG features, which are then combined with
      the temporal features to form a resultant efficient feature vector. For the
      classification scheme, we selected the feed-forward artificial neural networks
      (ANNs) optimally designed by the multi-dimensional particle swarm optimization
      (MD-PSO) technique, which evolves the structure and weights of the network
      specifically for each patient. Training data for the ANN classifier include both
      global (total of 150 representative beats randomly sampled from each class in
      selected training files) and local (the first 5 min of a patient's ECG recording)
      training patterns. Simulation results using 40 files in the MIT/BIH arrhythmia
      database achieved high average accuracy of 97% for differentiating normal, PVC,
      and other beats.

PMID- 19163955
TI  - Phase space reconstruction approach for ventricular arrhythmias characterization.
AB  - Ventricular arrhythmias, especially tachycardia and fibrillation are one of the
      main causes of sudden cardiac death. Therefore, the development of methodologies,
      enable to detect their occurrence and to characterize their time evolution, is of
      fundamental importance. This work proposes a non-linear dynamic signal processing
      approach to address the problem. Based on the phase space reconstruction of the
      electrocardiogram (ECG), some features are extracted for each ECG time window.
      Features from current and previous time windows are provided to a dynamic neural
      network classifier, enabling arrhythmias detection and evolution trends
      assessment. Sensitivity and specificity values, evaluated from public MIT-BIH
      databases, show the effectiveness of the proposed strategy.

PMID- 19163957
TI  - A covariance-based algorithm: a novel technique for rhythm discrimination in
      ICDs.
AB  - Inappropriate shocks due to misclassification of supraventricular and ventricular
      arrhythmias remain a major problem in the care of patients with Implantable
      Cardioverter defibrillators (ICDs). In this study we have investigated the
      ability of a new covariance-based algorithm, to distinguish Ventricular
      Tachycardia from other rhythms such as Supraventricular Tachycardia. The proposed
      algorithm has a low computational demand and with a small adjustment is
      applicable on both single-chamber and dual-chamber ICDs. The results are
      promising and suggest that the new covariance-based algorithm may be an effective
      method for ICD rhythm classification and may decrease inappropriate shocks.

PMID- 19163958
TI  - Detection of atrial fibrillation episodes using multiple heart rate variability
      features in different time periods.
AB  - Circadian variations of cardiac diseases have been well known. For example,
      atrial fibrillation (AF) episodes show nocturnal predominance. In this study, we
      have developed multiple formulas that detect AF episodes in different times of
      the day. Heart rate variability features were calculated from randomly sampled
      three min ECG data. Logistic regression analyses were performed to generate three
      formulas for the entire day, daytime, and evening time. Compared to the first
      formula that disregarded the time of the day, the second formula for the daytime
      detection detected AF episodes more accurately (95.2% vs. 99.3%), whereas third
      formula for the evening time detection did less accurately (93.8%). These results
      suggest the detection of AF episodes might become more accurate by considering
      the time-dependent changes of HRV features. In addition, the detection method for
      the evening time requires further investigation.

PMID- 19163959
TI  - Investigation of photoplethysmogram morphology for the detection of hypovolemic
      states.
AB  - Medics and first responders to emergencies are often faced with monitoring and
      assessing victims with very limited resources. Therefore, there is an inherent
      need for a real-time ambulatory monitoring capability that is portable and low
      power. This is particularly important for physiological monitoring of life
      threatening conditions such as internal hemorrhaging. We propose the use of
      photoplethysmogram (PPG) morphology as an indicator of hypovolemic states and
      study its correlation with blood pressure. In this paper, we compared the PPG
      morphology with pulse transit time (PTT), which has been investigated for
      clinical and ambulatory applications. The indicators were tested on data obtained
      from experiments using lower body negative pressure (LBNP) as a model to simulate
      hemorrhage in humans. The results of this study indicate that PPG morphology is
      associated with pulse pressure (systolic minus diastolic blood pressure) and is
      therefore a promising feature for detection and real-time tracking of hypovolemic
      states.

PMID- 19163960
TI  - A low cost quadratic level ECG compression algorithm and its hardware
      optimization for body sensor network system.
AB  - A low cost quadratic level compression algorithm is proposed for body sensor
      network system. The proposed algorithm reduces the encoding delay and the
      hardware cost, while maintaining the reconstructed signal quality. The quadratic
      compression level determined by the mean deviation value is used to preserve the
      critical information with high compression ratio. The overall CR is 8.4:1, the
      PRD is 0.897% and the encoding rate is 6.4 Mbps. The 16-bit sensor node processor
      is designed, which supports the proposed compression algorithm. The processor
      consumes 0.56 nJ/bit at 1 V supply voltage with 1 MHz operating frequency in 0.25
      microm CMOS process.

PMID- 19163961
TI  - Correlations of diffusion tensor imaging values and symptom scores in patients
      with schizophrenia.
AB  - Abnormalities in white matter (WM) brain regions are attributed as a possible
      biomarker for schizophrenia (SZ). Diffusion tensor imaging (DTI) is used to
      capture WM tracts. Psychometric tests that evaluate the severity of symptoms of
      SZ are clinically used in the diagnosis process. In this study we investigate the
      correlates of scalar DTI measures, such as fractional anisotropy, mean
      diffusivity, axial diffusivity, and radial diffusivity with behavioral test
      scores. The correlations were found by different schemes: mean correlation with
      WM atlas regions and multiple regression of DTI values with test scores. The
      corpus callosum, superior longitudinal fasciculus right and inferior longitudinal
      fasciculus left were found to be having high correlations with test scores.

PMID- 19163962
TI  - An MR-DTI-based fiber tracking method for the multimodal integrative study of
      cognitive brain functions.
AB  - We have developed a method for white matter fiber tracking inferred from magnetic
      resonance diffusion tensor imaging (MR-DTI) to match functional and anatomical
      information in the human brain. Functional information was obtained using
      functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG).
      One of the major problems in fiber tracking based on MR-DTI is the error of fiber
      orientation estimation at areas of fiber crossing. Here, we propose a novel fiber
      tracking method involving searching for similarity of direction vectors in the
      vicinity of fiber crossing areas. The proposed method was tested on simulation
      images and its utility was validated. Subsequently, the method was applied to in
      vivo data, and we tried to fuse the data obtained with the method with functional
      information obtained from a newly developed fMRI-MEG integrative method. The fMRI
      MEG integrative method successfully detected dynamic cortical activities in
      multiple visual areas, such as V1, V2, and V5, during an apparent visual motion
      perception task. Our fiber tracking results demonstrate that the present method
      can be used to confirm connectivity among multiple cortical areas associated with
      higher cognitive brain functions.

PMID- 19163963
TI  - Segmentation of diffusion-weighted brain images using expectation maximization
      algorithm initialized by hierarchical clustering.
AB  - Tissue segmentation based on diffusion-weighted images (DWI) provides
      complementary information of tissue contrast to the structural MRI for
      facilitating the tissue segmentation. In the previous literatures, DWI-based
      brain tissue segmentation was carried out using the parametric images, such as
      fractional anisotropy (FA) and apparent diffusion coefficient (ADC). However, the
      information of directions of neural fibers was very limited in the parametric
      images. To fully utilize the directional information, we propose a novel method
      to perform tissue segmentation directly on the DWI raw image data. Specifically,
      a hierarchical clustering (HC) technique was first applied on the down-sampled
      data to initialize the model parameters for each tissue cluster followed by
      automatic segmentation using the expectation maximization (EM) algorithm. The
      whole brain DWI raw data of five normal subjects were analyzed. The results
      demonstrated that HC-EM is effective in multi-tissue classification on DWI raw
      data.

PMID- 19163964
TI  - Evaluation of Alzheimer's disease by analysis of MR images using Objective
      Dialectical Classifiers as an alternative to ADC maps.
AB  - Alzheimer's disease is the most common cause of dementia, yet hard to diagnose
      precisely without invasive techniques, particularly at the onset of the disease.
      This work approaches image analysis and classification of synthetic multispectral
      images composed by diffusion-weighted (DW) magnetic resonance (MR) cerebral
      images for the evaluation of cerebrospinal fluid area and measuring the advance
      of Alzheimer's disease. A clinical 1.5 T MR imaging system was used to acquire
      all images presented. The classification methods are based on Objective
      Dialectical Classifiers, a new method based on Dialectics as defined in the
      Philosophy of Praxis. A 2-degree polynomial network with supervised training is
      used to generate the ground truth image. The classification results are used to
      improve the usual analysis of the apparent diffusion coefficient map.

PMID- 19163965
TI  - A method to classify schizophrenia using inter-task spatial correlations of
      functional brain images.
AB  - The clinical heterogeneity of schizophrenia (scz) and the overlap of self
      reported and observed symptoms with other mental disorders makes its diagnosis a
      difficult task. At present no laboratory-based or image-based diagnostic tool for
      scz exists and such tools are desired to support existing methods for more
      precise diagnosis. Functional magnetic resonance imaging (fMRI) is currently
      employed to identify and correlate cognitive processes related to scz and its
      symptoms. Fusion of multiple fMRI tasks that probe different cognitive processes
      may help to better understand hidden networks of this complex disorder. In this
      paper we utilize three different fMRI tasks and introduce an approach to classify
      subjects based on inter-task spatial correlations of brain activation. The
      technique was applied to groups of patients and controls and its validity was
      checked with the leave-one-out method. We show that the classification rate
      increases when information from multiple tasks are combined.

PMID- 19163966
TI  - An automatic segmentation approach for boundary delineation of corpus callosum
      based on cell competition.
AB  - The size and shape of corpus callosum are important indicators for assisting
      diagnosis of many neurological diseases involving morphological changes of corpus
      callosum. A new automatic segmentation approach was proposed in this paper for
      boundary delineation of corpus callosum. The basic idea of the proposed approach
      was to perform segmentation on the red component of color-coded map of diffusion
      tensor magnetic resonance image (MR-DTI). The boundary of corpus callosum was
      delineated in two phases. Firstly, a rough boundary surrounding corpus callosum
      was derived by using a built-in contour function in Matlab. Then, this cell
      competition algorithm was applied to the area inside the rough boundary derived
      in the first phase. The proposed segmentation approach has been evaluated and
      compared to the Chan and Vese level set method by using the MR-DTI images of a
      healthy volunteer and a systemic lupus erythematorsus (SLE) patient. The
      implementation results showed that the proposed approach could delineate the
      boundaries of corpus callosum reasonably well for both cases, whereas the Chan
      and Vese level set method failed to catch the weak edge for the SLE patient.

PMID- 19163967
TI  - Neural computation in the binocular VOR circuit: a theoretical study.
AB  - We present here a bilateral model for the horizontal rotational vestibulo-ocular
      reflex (VOR) that integrates sigmoidal nonlinearities in the response of VOR
      interneurons. This model realistically links the systems level approach to the
      underlying neural mechanisms. It is capable of producing VOR modulations with
      viewing context using only the efference copies of eye position signals to make
      novel predictions.

PMID- 19163968
TI  - Functional connectivity through nonlinear modeling: an application to the rat
      hippocampus.
AB  - Implementation of neuroprosthetic devices requires a reliable and accurate
      quantitative representation of the input-output transformations performed by the
      involved neuronal populations. Nonparametric, data driven models with predictive
      capabilities are excellent candidates for these purposes. When modeling input
      output relations in multi-input neuronal systems, it is important to select the
      subset of inputs that are functionally and causally related to the output. Inputs
      that do not convey information about the actual transformation not only increase
      the computational burden but also affect the generalization of the model.
      Moreover, a reliable functional connectivity measure can provide patterns of
      information flow that can be linked to physiological and anatomical properties of
      the system. We propose a method based on the Volterra modeling approach that
      selects distinct subsets of inputs for each output based on the prediction of the
      respective models and its statistical evaluation. The algorithm builds successive
      models with increasing number of inputs and examines whether the inclusion of
      additional inputs benefits the predictive accuracy of the overall model. It also
      explores possible second-order (inter-modulatory) interactions among the inputs.
      The method was applied to multi-unit recordings from the CA3 (input) and CA1
      (output) regions of the hippocampus in behaving rats, in order to reveal
      spatiotemporal connectivity maps of the input-output transformation taking place
      in the CA3-CA1 synapse.

PMID- 19163969
TI  - A functional approach to modeling M1 single-unit activity recorded in three
      primate motor control studies.
AB  - When monkeys make movements with or without external force perturbations, or
      generate isometric forces in different directions from different workspace
      positions, primary motor cortex (M1) cell activity shows systematic changes in
      directional tuning and in force-generation gains as a function of arm posture.
      However, it may be simplistic to assume most control intelligence is in the
      cortex while the brainstem and especially the spinal cord do little more than
      passively implement pontifical descending commands. More recent studies like [1
      4] do suggest a different perspective. Furthermore, systematic changes in
      directionality of M1 cell and limb muscle EMG activity may stem partly from the
      feedback (aka reflex) loops, physical properties of limb biomechanics, muscle
      anisotropy and force production nonlinearities, and their interplay with task
      conditions, and not only due to predictive feedforward central commands.

PMID- 19163970
TI  - Reconstructing functional neuronal circuits using dynamic Bayesian networks.
AB  - Identifying functional connectivity from simultaneously recorded spike trains is
      important in understanding how the brain processes information and instructs the
      body to perform complex tasks. We investigate the applicability of dynamic
      Bayesian networks (DBN) to infer the structure of neural circuits from observed
      spike trains. A probabilistic point process model was used to assess the
      performance. Results confirm the utility of DBNs in inferring functional
      connectivity as well as directions of signal flow in cortical network models.
      Results also demonstrate that DBN outperforms the Granger causality when applied
      to populations with highly non-linear synaptic integration mechanisms.

PMID- 19163971
TI  - Control theory-based regulation of hippocampal CA1 nonlinear dynamics.
AB  - We are developing a biomimetic electronic neural prosthesis to replace regions of
      the hippocampal brain area that have been damaged by disease or insult. Our
      previous study has shown that the VLSI implementation of a CA3 nonlinear dynamic
      model can functionally replace the CA3 subregion of the hippocampal slice. As a
      result, the propagation of temporal patterns of activity from DG-->VLSI-->CA1
      reproduces the activity observed experimentally in the biological DG-->CA3-->CA1
      circuit. In this project, we incorporate an open-loop controller to optimize the
      output (CA1) response. Specifically, we seek to optimize the stimulation signal
      to CA1 using a predictive dentate gyrus (DG)-CA1 nonlinear model (i.e., DG-CA1
      trajectory model) and a CA1 input-output model (i.e., CA1 plant model), such that
      the ultimate CA1 response (i.e., desired output) can be first predicted by the DG
      CA1 trajectory model and then transformed to the desired stimulation through the
      inversed CA1 plant model. Lastly, the desired CA1 output is evoked by the
      estimated optimal stimulation. This study will be the first stage of formulating
      an integrated modeling-control strategy for the hippocampal neural prosthetic
      system.

PMID- 19163972
TI  - Effects of I(h) and I(KLT) on the response of the auditory nerve to electrical
      stimulation in a stochastic Hodgkin-Huxley model.
AB  - An accurate model of auditory nerve fibers (ANFs) would help in improving
      cochlear implant (CI) functionality. Previous studies have shown that the
      original Hodgkin-Huxley (1952) model (with kinetics adjusted for mammalian body
      temperature) may be better at describing nodes of Ranvier in ANFs than models for
      other mammalian axon types. However, the HH model is still unable to explain a
      number of phenomena observed in auditory nerve responses to CI stimulation such
      as long-term accommodation, adaptation and the time-course of relative
      refractoriness. Recent physiological investigations of spiral ganglion cells have
      shown the presence of a number of ion channel types not considered in the
      previous modeling studies, including low-threshold potassium (I(KLT)) channels
      and hyperpolarization-activated cation (I(h)) channels. In this paper we
      investigate inclusion of these ion channel types in a stochastic HH model. For
      single biphasic charge-balanced pulse, an increase in spike threshold was
      typically produced by inclusion of one or both of these channel types. The
      addition of I(KLT) increases random threshold fluctuations in the stochastic
      model, particularly for longer pulse widths. Pulse-train responses were
      investigated for pulse rates of 200, 800, and 2000 pulse/s. Initial results
      suggests that both the I(KLT) channels and I(h) channels can produce adaptation
      in the spike rate. However, the adaptation due to I(KLT) is restricted to higher
      stimulation rates, whereas the adaptation due to I(h) is observed across all
      stimulation rates.

PMID- 19163973
TI  - Automation in anesthesia: computer controlled propofol infusion and data
      acquisition.
AB  - This work presents the improvement of a software for a clinical setup, the
      Anesthesia Synchronization Software (ASYS). The first version presented the data
      acquisition from cerebral monitors and a partial control with Target Controlled
      Infusion (TCI) system. Based on pharmacokinetic models, the effect-site and
      plasma concentrations can be related with the drug dose infused and vice versa.
      This later version comes with the implementation of the hemodynamic monitor
      always present in operating rooms and with the full TCI system developed to
      determine the infusion rates of the drug which are given as commands to the
      infusion pumps.

PMID- 19163974
TI  - Theoretical modelling to understand the neurotransmission mechanism in the
      gastrointestinal tract.
AB  - In this paper we apply a novel experimental and theoretical method to study the
      neurotransmitter signalling process. This method allows the understanding of
      changes in uptake between different tissue types from the gastrointestinal tract.
      The reaction-diffusion model we used has shown that by changing the uptake rate,
      the slope of the response changed when the levels of 5-HT released were held
      constant. Experimental data from the ileum and colon obtained at one distance
      from the tissue shows no significant difference in the release profile, however
      measurements at multiple sites show different current slopes for the two tissues.
      The response based upon the theoretical data indicates that colon has a higher
      uptake rate than the ileum. These results show that the combination of a
      theoretical and experimental approach to study biological processes can provide a
      mean of gaining further inside into the mechanisms involved and can have
      important clinical applications.

PMID- 19163975
TI  - Validation of the Index of Consciousness (IoC) during sedation/analgesia for
      ultrasonographic endoscopy.
AB  - The level of consciousness of patients undergoing surgery evolves continuously as
      the effect of the anesthetic agents is counteracted by the surgical stimuli. The
      monitors of depth of anesthesia, based on the analysis of the
      electroencephalogram (EEG), have been progressively introduced into the daily
      practice to provide additional information about the state of the patient. In
      this work, the Index of Consciousness (IoC), a recent index which uses the
      information from EEG spectrum and symbolic dynamics through a fuzzy inference
      system, is introduced. The bispectral index BIS, a well-established index, is
      used to validate the IoC. A good correlation is found between both indexes.
      Furthermore, IoC presents a significantly higher prediction probability Pk of the
      level of sedation than BIS, and can thus be considered as an interesting measure
      of the level of consciousness.

PMID- 19163976
TI  - Wheel/tissue force interaction: a new concept for soft tissue diagnosis during
      MIS.
AB  - This paper describes a feasibility study of a novel force sensor that can be used
      to localise tissue abnormalities and provide tactile feedback to the surgeon
      during minimally invasive surgery. The proposed sensor makes use of an air
      supported rigid ball mounted at the end of a tubular shaft to indent the tissue
      under investigation. Variations in tissue stiffness which cause changes in
      position of the ball are measured by using an optical sensing scheme. The sensor
      enables rapid acquisition of tactile information over large areas of soft tissue.
      Laboratory experiments were conducted to demonstrate the feasibility of the
      proposed sensor system. The outcome of the conducted experiments shows similarity
      to the results from a cylindrical wheel-based force sensor [1] which are shown
      here for comparative purposes.

PMID- 19163977
TI  - Denoising of diaphragmatic electromyogram signals for respiratory control and
      diagnostic purposes.
AB  - Diaphragmatic electromyogram (EMGdi) signals give important information about the
      respiratory muscle pump, can be used as an indicator of neural respiratory drive,
      and have been postulated as a method of designing neurally-activated intelligent
      ventilators. However diaphragmatic EMG signals measured with an esophageal
      catheter tend to be contaminated by electrical signals from the heart
      electrocardiogram (ECG). This paper presents a novel method of rapidly separating
      and enhancing the Electromyogram signals from the combined EMG and ECG signals
      recorded from an esophageal catheter based sensor. Independent Component Analysis
      (ICA) is used to separate the EMG and ECG signals, then further processing is
      used to extract the frequency of the patient's breathing and the relative
      magnitudes of diaphragmatic muscle activity. These signals have two applications,
      firstly in artificial ventilator systems and as a diagnostic tool for health
      professionals.

PMID- 19163978
TI  - On the modeling of drug induced respiratory depression in the non-steady-state.
AB  - The ability of anesthetic agents to provide adequate analgesia and sedation is
      limited by the ventilatory depression associated with overdosing in spontaneously
      breathing patients. Therefore, quantitation of drug induced ventilatory
      depression is a pharmacokinetic-pharmacodynamic problem relevant to the practice
      of anesthesia. Although several studies describe the effect of respiratory
      depressant drugs on isolated endpoints, an integrated description of drug induced
      respiratory depression with parameters identifiable from clinically available
      data is not available. This study proposes a physiological model of CO2
      disposition, ventilatory regulation, and the effects of anesthetic agents on the
      control of breathing. The predictive performance of the model is evaluated
      through simulations aimed at reproducing experimental observations of drug
      induced hypercarbia and hypoventilation associated with intravenous
      administration of a fast-onset, highly potent anesthetic mu agonist (including
      previously unpublished experimental data determined after administration of 1 mg
      alfentanil bolus). The proposed model structure has substantial descriptive
      capability and can provide clinically relevant predictions of respiratory
      inhibition in the non-steady-state to enhance safety of drug delivery in the
      anesthetic practice.

PMID- 19163979
TI  - In vivo non-invasive high resolution MR-based method for the determination of the
      elastic modulus of arterial vessels.
AB  - The mechanical properties of arterial walls have long been recognized to play an
      essential role in the development and progression of cardiovascular disease
      (CVD). Early detection of variations in the elastic modulus of arteries would
      help in monitoring patients at high cardiovascular risk stratifying them
      according to risk. An in vivo, non-invasive, high resolution MR-phase-contrast
      based method for the estimation of the time-dependent elastic modulus of healthy
      arteries was developed, validated in vitro by means of a thin walled silicon
      rubber tube integrated into an existing MR-compatible flow simulator and used on
      healthy volunteers. A comparison of the elastic modulus of the silicon tube
      measured from the MRI-based technique with direct measurements confirmed the
      method's capability. The repeatability of the method was assessed. Viscoelastic
      and inertial effects characterizing the dynamic response of arteries in vivo
      emerged from the comparison of the pressure waveform and the area variation curve
      over a period. For all the volunteers who took part in the study the elastic
      modulus was found to be in the range 50-250 kPa, to increase during the rising
      part of the cycle, and to decrease with decreasing pressure during the downstroke
      of systole and subsequent diastole.

PMID- 19163980
TI  - Characterization of the viscosity and elasticity in soft tissue using dynamic
      finite elements.
AB  - An iterative solution to the inverse problem of elasticity and viscosity is
      proposed in this paper. A finite elements model has been derived to account for
      the viscoelastic changes in soft tissue that is consistent with known rheological
      models. Using this deformation model and the observed dynamic data, the viscosity
      and elasticity have been reconstructed in the medium by using a Gauss-Newton
      based approach. Previous knowledge of the parameters on the boundaries of the
      medium are necessary to assure uniqueness and convergence and to obtain an
      accurate map of the viscoelastic properties. The methods have been studied in FEM
      simulations and also tested through experiments, where the viscosity and
      elasticity of a gelatin based phantom with an inclusion of known properties have
      been reconstructed successfully.

PMID- 19163981
TI  - Statistical finite element analysis.
AB  - A novel technique is introduced for tissue deformation and stress analysis.
      Compared to the conventional Finite Element method, this technique is orders of
      magnitude faster and yet still very accurate. The proposed technique uses
      preprocessed data obtained from FE analyses of a number of similar objects in a
      Statistical Shape Model framework as described below. This technique takes
      advantage of the fact that the body organs have limited variability, especially
      in terms of their geometry. As such, it is well suited for calculating tissue
      displacements of body organs. The proposed technique can be applied in many
      biomedical applications such as image guided surgery, or virtual reality
      environment development where tissue behavior is simulated for training purposes.

PMID- 19163982
TI  - Methods for the estimation of sub-sample motion of digitized ultrasound echo
      signals in two dimensions.
AB  - Motion estimation in sequences of ultrasound echo signals is essential for a wide
      range of modern ultrasound-based signal processing applications. Pattern matching
      algorithms are generally used for finding the motion within sampling accuracy.
      Subsequently, 1D interpolation techniques are employed to find any motion smaller
      than sampling accuracy. In this paper, we propose several interpolation schemes
      that are suited for 2D motion estimation. Simulations using Field II ultrasound
      simulation software and experiments using an Ultrasonix Sonix RP imaging system
      with a L9-4/38 linear array transducer are used to study these techniques and
      compare their performance to other methods reported in the literature. The
      results show that the proposed interpolation methods outperform other common
      techniques in terms of bias and jitter. The axial and the lateral bias of the
      proposed methods are measured to be less than 1 microm and 5 microm,
      respectively, in both the simulated and the experimental data.

PMID- 19163983
TI  - Assessment of myofascial trigger points (MTrPs): a new application of ultrasound
      imaging and vibration sonoelastography.
AB  - Myofascial trigger points (MTrPs) are palpable hyperirritable nodules in skeletal
      muscle that are associated with chronic musculoskeletal pain. The goal of this
      study was to image MTrPs in the upper trapezius muscle using 2D gray scale
      ultrasound (US) and vibration sonoelastography (VSE) for differentiating the soft
      tissue characteristics of MTrPs compared to surrounding muscle. MTrPs appeared as
      hypoechoeic elliptically-shaped focal regions within the trapezius muscle on 2D
      US. Audio-frequency vibrations (100-250 Hz) were induced in the trapezius muscle
      of four volunteers with clinically identifiable MTrPs, and the induced vibration
      amplitudes were imaged using the color Doppler variance mode, and were further
      quantified using spectral Doppler analysis. Spectral Doppler analysis showed that
      vibration amplitudes were 27% lower on average within the MTrP compared to
      surrounding tissue (p0.05). Color variance imaging consistently detected a focal
      region of reduced vibration amplitude, which correlated with the hypoechoeic
      region identified as an MTrP (r =0.76 for area). Real-time 2D US identifies
      MTrPs, and VSE is feasible for differentiating MTrPs from surrounding tissue.
      Preliminary findings show that MTrPs are hypoechoeic on 2D US and the relative
      stiffness of MTrPs can be quantified using VSE. Ultrasound offers a convenient,
      accessible and low-risk approach for identifying MTrPs and for evaluating
      clinical observations of palpable, painful nodules.

PMID- 19163984
TI  - Robotic system for tumor manipulation and ultrasound image guidance during breast
      biopsy.
AB  - Tumor mobility poses significant difficulty in obtaining tissue samples during
      ultrasound guided breast biopsy. In this work, we present a new concept for
      coordinated real-time tumor manipulation and ultrasound imaging using a hybrid
      control architecture. The idea here is to demonstrate that it is possible to (1)
      manipulate a tumor in real-time by applying controlled external force, (2)
      control the position of the ultrasound probe for tracking out-of-plane target
      movement, and (3) coordinate the above systems in an automated way such that the
      tumor does not deviate from the path of the needle. Experiments are performed on
      breast tissue mimicking phantoms to demonstrate the efficacy of this technique.
      The success of this approach has the potential to reduce the number of attempts a
      surgeon makes to capture the desired tissue specimen, minimize tissue damage,
      improve speed of biopsy, and reduce patient discomfort.

PMID- 19163985
TI  - Conception and design of an automated insertion tool for cochlear implants.
AB  - Cochlear implants (CI) are electronic devices incorporating an electrode inserted
      into the human cochlea for direct electric stimulation of the auditory nerve. The
      implantation has become the standard treatment for patients with severe-to
      profound sensorineural loss not aidable with conventional hearing aids. The state
      of the art operative technique is a facial recess approach to the middle ear,
      following the opening of the scala tympani (cochleostomy) and insertion of the
      electrode array. The facial recess approach is applicable only by experienced
      surgeons and optimal CI results primarily depend on optimal electrode placement
      and minimal traumatic insertion. This also requires a certain amount of
      experience. Additionally several groups work on minimally-invasive approaches to
      the cochlea, resulting in the necessity to insert the implant via a keyhole
      access, which is not applicable with current techniques. This paper presents a
      mechatronic device for an automated insertion of the electrode array of a
      cochlear implant system. Being designed especially for minimally-invasive
      approaches, the tool is also applicable for regular facial recess approaches.
      Moreover the device allows reliable and repeatable insertion studies at synthetic
      models or cadaver specimen. The functionality of the tool is proofed with first
      experiments on a synthetic model.

PMID- 19163986
TI  - TeleRobotic fundamentals of laparoscopic surgery (FLS): effects of time delay-
      pilot study.
AB  - Within the area of telerobotic surgery no standardized means of surgically
      relevant performance evaluation has been established. The Society of American
      Gastrointestinal and Endoscopic Surgeons (SAGES) Fundamentals of Laparoscopic
      Surgery (FLS) program provides a set of standardized tasks that are considered
      the 'gold standard' in surgical skill assessment. We present a methodology for
      using one of the SAGES FLS tasks for surgical robotic performance evaluation. The
      TeleRobotic FLS methodology is extendable to two other FLS tasks. Time delay in
      teleoperation in general and telesurgery in particular is one of the fundamental
      effects that limits performance in telerobotic surgery. In this pilot study the
      effect of time delay on the Block Transfer task performance was investigated. The
      RAVEN Surgical Robot was used in a master/slave configuration in which time
      delays of 0, 250, 500, and 1000 ms were introduced by a network emulator between
      the master (Surgeon Site) and the slave (Patient Site). The study included three
      subjects, each of whom was presented with three of the four conditions. The
      results show that one subject had a lower error rate with increasing time delay,
      whereas the other subjects had a higher error rate with increased delay. The
      subject with the longest average completion time suffered the least performance
      decrease under time delay.

PMID- 19163987
TI  - Design of a small animal biopsy robot.
AB  - Small animals are widely used in biomedical research studies. They have compact
      anatomy and small organs. Therefore it is difficult to perceive tumors or cells
      and perform biopsies manually. Robotics technology offers a convenient and
      reliable solution for accurate needle insertion. In this paper, a novel 5 degrees
      of freedom (DOF) robot design for inserting needles into small animal subjects is
      proposed. The design has a compact size, is light weight, and has high
      resolution. Parallel mechanisms are used in the design for stable and reliable
      operation. The proposed robot has two gimbal joints that carry the needle
      mechanism. The robot can realize dexterous alignment of the needle before
      insertion.

PMID- 19163988
TI  - First 3D ultrasound scanning, planning, and execution of CT-free milling
      interventions with a surgical robot.
AB  - Surgical procedures with navigation or robot system support usually require pre
      operative planning data. This data can be acquired with imaging techniques such
      as computed tomography (CT), the current gold standard due to its high precision.
      With such planning data, access trajectories, implant positions, individual
      milling paths etc. can be computed. We present a novel ultrasound-based method to
      generate equivalent 3D image data which is well-suited for many interventions,
      but less costly than the CT-based method. The method is demonstrated for robot
      based implant bed milling in the lateral skull base, in a complete process
      consisting of infrared navigation registration, manual ultrasound scan path
      delineation, path smoothing and checking, robot-based ultrasound scan execution,
      3D ultrasound volume reconstruction, implant position optimization, robot milling
      path planning, and intervention execution. This represents, to the best of our
      knowledge, the first time such a CT-free, 3D-ultrasound-based intervention has
      been demonstrated in the laboratory.

PMID- 19163989
TI  - Biologically inspired microtexturing: investigation into the surface topography
      of next-generation neurosurgical probes.
AB  - Minimally Invasive (MI) surgery represents the future of many types of medical
      intervention (keyhole neurosurgery, natural orifice trans-luminal endoscopic
      surgery, etc.). However, the shortcomings of today's surgical tools fuel the need
      for the development of next-generation 'smart instrumentation', which will be
      more accurate and safer for the patient. This paper presents the preliminary
      results of a biologically inspired microtexturing method, based on UV
      lithography, and its application to MI neurosurgery. These results suggest that
      the size and geometry of the texture 'printed' on the outer surface of a
      neurosurgical probe clearly affect the insertion and extraction forces generated
      at the brain-probe interface. Thus, by carefully choosing an appropriate
      microtexture, unique insertion characteristics can be obtained, which can improve
      the performance of existing instruments (e.g. reducing slippage in permanent
      electrodes such as those used in deep brain stimulation) or enable the
      development of novel designs altogether.

PMID- 19163990
TI  - Diamagnetically-stabilized levitation control of an intraluminal magnetic
      capsule.
AB  - Controlled navigation promotes full utilization of capsule endoscopy for reliable
      real-time diagnosis in the gastrointestinal (GI) tract, but intermittent natural
      peristalsis can disturb the navigational control, destabilize the capsule and
      take it out of levitation. A real-size magnetic navigation system that can handle
      peristaltic forces of up to 1.5 N was designed utilizing the computer-aided
      design (CAD) system Maxwell 3D (Ansoft, Pittsburg, PA), and was verified using a
      small-size physical experimental setup. The proposed system contains a pair of 50
      cm in diameter, 10,000-turns copper electromagnets with a 10-cm by 10-cm ferrous
      core driven by currents of up to 300 Amperes and can successfully maintain
      position control over the levitating capsule during peristalsis. The addition of
      Bismuth diamagnetic casing for stabilizing the levitating capsule was also
      studied.

PMID- 19163991
TI  - Objective assessment of knee osteroarthritis in parachuters by bioimpedance
      spectroscopy.
AB  - The aim of the present study was to derive an objective and noninvasive
      assessment of osteoarthritis of the knee joint by bioimpedance spectrocopy (BIS).
      The study was performed in Brazilian Military Parachuters and intends to
      contribute to the improvement of the early diagnosis of joint degeneration.
      Twelve male volunteers (24 knee joints) participated in the study. A novel index
      (ID) to assess the disease was proposed from the raw bioimpedance parameter. This
      index was compared with a subjective rating (Dejour scale) performed by 3
      therapists. The results indicated that the values of ID were significantly
      different (p0.001) between the control group (class 1 of Dejour) and the
      pathological group (class 2 or higher). A Spearman correlation of -0.81 between
      the values of ID and the therapists rating was detected. Despite the need of
      increasing the sample size, the novel technique seems to be capable of supplying
      an objective and non-invasive tool for helping the diagnosis of the knee
      osteoarthritis.

PMID- 19163992
TI  - Performance verification of a prototype non-invasive intra-oral bone growth
      stimulator for titanium dental implants.
AB  - A prototytpe non-invasive intra-oral device to promote bone growth following
      dental implantation was developed. The device generates a pulsed electromagnetic
      field (PEMF) covering the bone interface of the titanium implant. The prescribed
      treatment period is two hours per day for eight-week duration. It is designed to
      be a single-patient use disposable device. All components are totally embedded
      into a mouth guard type enclosure so that it can be conveniently and comfortably
      placed inside and removed from the oral cavity by the patient. Laboratow
      verification tests confirmed the device meets the designed technical
      specifications. Initial in-vitro study showed positive results in promoting bone
      growth.

PMID- 19163993
TI  - Measurement and evaluation of finger tapping movements using magnetic sensors.
AB  - This paper proposes a quantitative measurement and evaluation method of finger
      tapping movements for diagnosis support and assessment of motor function. In this
      method, a magnetic sensor consisting of two coils is used to measure movement.
      The coil voltage induced by the electromagnetic induction law changes depending
      on the distance between the two coils; this enables estimation of the distance
      between two coil-bearing fingertips from the voltage measured by the nonlinear
      modeling relationships between the voltages and distances. Further, the finger
      movements measured are evaluated by computing ten indices such as the finger
      tapping interval, and radar charts of the evaluation indices and phase-plane
      trajectories of the finger movements are then displayed in real time on a
      monitor. Evaluation experiments were performed on finger movement in 16
      Parkinson's disease patients and 32 normal elderly subjects, with the results
      showing that all evaluation indices differ significantly for each subject (p <<
      0.05).

PMID- 19163994
TI  - Evaluating automatically generated personalized interfaces on an ergometer for
      people with diverse abilities.
AB  - The MedURC (Medical Universal Remote Console) technology uses a collection of
      standards to create universal interfaces for various medical equipment, including
      user information on preferences and capabilities to create a personalized
      accessible interface. This project significantly extends MedURC by supporting an
      ad hoc fitness industry communication standard for that makes it possible for
      MedURC to operate any other supported exercise equipment. A variety of
      alternative interfaces (default, universally designed, personalized) were
      evaluated by subjects that included persons with disabilities and older adults,
      using performance data while executing specific tasks and subject interviews.
      Results show that subjects prefer and perform better on a personalized interface.

PMID- 19163995
TI  - An efficient BiCGstab solved impedance method for induced field evaluation with a
      hyperthermia applicator.
AB  - This paper presents a stabilized Bi-conjugate gradient algorithm that can
      significantly improve the performance of the impedance method, which has been
      widely applied to model low-frequency field induction phenomena in voxel
      phantoms. The improved quasi-static impedance method offers remarkable
      computational advantages in terms of convergence performance and memory
      consumption over the conventional, stationary iterative method-based algorithm.
      The scheme has been validated against other numerical/analytical solutions on a
      lossy, multilayered sphere phantom with an ideal coil loop excitation. To further
      demonstrate the computational performance and application capability of the
      developed algorithm, the induced fields inside a whole body human phantom
      responding to hyperthermia device was evaluated. The simulation results show the
      numerical accuracy and superior performance of the method.

PMID- 19163996
TI  - Design and implementation of a two degree-of-freedom micromanipulation assessment
      system.
AB  - A two degree-of-freedom (DOF) micro motion sensing system to assess
      micromanipulation accuracy and physiological tremor has been developed. The
      system employs a position sensitive detector (PSD) module and a laser diode
      placed inside an instrument used in micromanipulation. A laser light is shined
      from the laser diode onto the PSD surface which is faced upward. The PSD detects
      the centroid position of the laser light spot falling onto its surface. A few
      markers are overlaid in a circular pattern on the PSD surface as reference for
      path dependent tests. Ambient light disturbance is eliminated by modulating the
      laser light on and off. Advantages and limitation of the system comparing to
      other similar systems are described.

PMID- 19163997
TI  - Photoacoustic depth profiling of a skin model for non-invasive glucose
      measurement.
AB  - A measurable depth of the blood glucose level by using photoacoustic spectroscopy
      (PAS) was discussed experimentally in order to improve detection sensitivity.
      Since a measurable depth of the PAS depends on a modulation frequency of the
      chopped light irradiated to a sample, the relationship between modulation
      frequency and the thickness of a sample was evaluated. The photoacoustic detector
      used in these experiments consisted of an acoustic resonance pipe and an optical
      microphone, and a two-layer model composed of silicone sheets with the different
      optical absorption. The measurable depth was 2-3 mm with modulation frequency of
      1000-2000 Hz. Furthermore, the reason for the measurable depth to be deeper than
      the thermal diffusion length of the sample was discussed theoretically. From
      these analyses of thermoelastic wave, the relation between the photoacoustic
      signal propagation and the measurable depth in a tissue was clarified.

PMID- 19163998
TI  - A 12-channel, real-time near-infrared spectroscopy instrument for brain-computer
      interface applications.
AB  - A continuous wave near-infrared spectroscopy (NIRS) instrument for brain-computer
      interface (BCI) applications is presented. In the literature, experiments have
      been carried out on subjects with such motor degenerative diseases as amyotrophic
      lateral sclerosis, which have demonstrated the suitability of NIRS to access
      intentional functional activity, which could be used in a BCI as a communication
      aid. Specifically, a real-time, multiple channel NIRS tool is needed to realise
      access to even a few different mental states, for reasonable baud rates. The 12
      channel instrument described here has a spatial resolution of 30 mm, employing a
      flexible software demodulation scheme. Temporal resolution of approximately 100
      ms is maintained since typical topographic imaging is not needed, since we are
      only interested in exploiting the vascular response for BCI control. A simple
      experiment demonstrates the ability of the system to report on haemodynamics
      during single trial mental arithmetic tasks. Multiple trial averaging is not
      required.

PMID- 19163999
TI  - SU-8 polymer enclosed microchannels with interconnect and nanohole arrays as an
      optical detection device for biospecies.
AB  - We present for the first time the integration of nanohole arrays for surface
      plasmon resonance (SPR) sensing together with SU-8 polymer microfluidic channels
      containing special packaging structures for chip-to-chip and world-to-chip
      interconnect. Primary steps towards an optical biospecies detection device are
      presented including observing the effect of period on transmission peak location,
      examining new materials for the enclosed microchannels, and demonstrating
      nanohole array SPR transmission data through water contained in the
      microchannels. Additionally, the enclosed microchannels are integrated with
      interconnect structures that facilitate interfacing with macro-scale test
      equipment and microfluidic components and systems such as lab-on-a-chip. Results
      demonstrate the potential of the polymer microchannels with integrated nanohole
      arrays and interconnect as a packaged optical SPR detection device.

PMID- 19164000
TI  - Optical instrument design for interrogation of dermally-implanted luminescent
      microparticle sensors.
AB  - Luminescence-based sensors have been developed in microparticle formats for
      biochemical targets such as glucose, enabling use of dermal implants for on
      demand monitoring. For these to be deployed and interrogated in vivo, a matched
      optoelectronic system for delivery of excitation, collection and analysis of
      luminescence response is needed. In this work, simulations based on Monte Carlo
      ray-tracing were performed for models of luminescent microparticle materials
      embedded in skin. The spectral and spatial distribution of luminescence escaping
      the skin was determined for different concentrations, implantation depths, and
      input beam sizes. Results indicate that the implant environment does not
      significantly alter the measured spectral intensity ratios. The escaping emission
      light possesses measurable power and spectral information for quantitative
      analysis. Using these findings, an optical system has been designed specifically
      for sensor interrogation and response acquisition, and is currently implemented
      in hardware. Following benchtop validation and signal-to-noise maximization with
      tissue phantoms, the instrument will be used for measurement on sensors in rat
      subjects.

PMID- 19164002
TI  - Predicting imminent episodes of ventricular tachyarrhythmia--retrospective
      analysis of short R-R records from ICD.
AB  - A predictor of an imminent episode of ventricular tachyarrhythmia, namely
      ventricular tachycardia and ventricular fibrillation has been developed. It only
      uses R-R records. The previous work was based on long R-R records stored in the
      memory of implantable cardioverter-defibrillators. With 1.8 hour of data,
      sensitivity of 53-83% can be achieved with corresponding specificity of 57-91%,
      depending on which set of criteria are used. The Medtronic ICD data series was
      made available to us. This consists of 135 pairs of files with 1024 R-R
      intervals. Each pair consists of a record that ends with the detection of the
      tachyarrhythmia, and a 'most recent' record just prior to the interrogation of
      the device. It was hoped that the 'most recent' record can be used to improve the
      specificity of the prediction algorithm. The predictor pattern was found in 29%
      of the arrhythmic records, and in 38% of the records with heart rate variability,
      namely SDNN, greater than 20 ms. This is comparable to the 40% results for
      similar conditions found earlier for records only 0.2 hr long. Unfortunately, due
      to a 'white coat effect', the predictor pattern was found in 40% of the 'most
      recent' records. While this new set of data has confirmed the sensitivity of the
      arrhythmia predictor, a fault in the data collection process this data set did
      not add to our understanding of the predictor behavior with a normal heart
      rhythm.

PMID- 19164001
TI  - Combining multiple microarray studies using bootstrap meta-analysis.
AB  - Microarray technology has enabled us to simultaneously measure the expression of
      thousands of genes. Using this high-throughput data collection, we can examine
      subtle genetic changes between biological samples and build predictive models for
      clinical applications. Although microarrays have dramatically increased the rate
      of data collection, sample size is still a major issue in feature selection.
      Previous methods show that microarray data combination is successful in improving
      selection when using z-scores and fold change. We propose a wrapper based gene
      selection technique that combines bootstrap estimated classification errors for
      individual genes across multiple datasets. The bootstrap is an unbiased estimator
      of classification error and has been shown to be effective for small sample data.
      Coupled with data combination across multiple data sets, we show that this meta
      analytic approach improves gene selection.

PMID- 19164003
TI  - Usefulness of monitoring congestive heart failure by multiple impedance vectors.
AB  - INTRODUCTION: We investigated trends in intrathoracic impedance measured between
      multiple implanted electrodes for monitoring pulmonary edema secondary to
      congestive heart failure (CHF) in an experimental model. METHODS: Biventricular
      ICDs were implanted in 16 dogs and 5 sheep. Continuous RV pacing (230- 250 bpm)
      was applied over several weeks. Meanwhile, impedance was measured every hour
      along 4 intrathoracic and 2 intracardiac vectors. Four cardiogenic impedance
      vectors were also monitored. Cardiac function was assessed biweekly by
      catheterization and echocardiography. Left atrial (LA) pressure was measured
      daily by an implanted LA pressure sensor. RESULTS: All animals developed CHF
      after 2-4 weeks of pacing as evidenced by changes in function (EF, 52 vs. 34%; LV
      end-diastolic volume, 65 vs. 97 ml; LV end-diastolic pressure, 7 vs. 16 mmHg; LA
      volume, 17 vs. 33 ml; LA pressure, 7 vs. 26 mmHg), clinical symptoms, or autopsy.
      Steady state impedance decreased during CHF: LV-Can, 17+/-9%; LV-RV, 15+/-8%; LV
      RA, 13+/-6%; RV-Can, 13+/-8%; RVcoil-Can, 8+/-6%; RA-Can, 6+/-6%. Change in LV
      Can impedance was greater than that of RA-Can, RV-Can, and RVcoil-Can (P0.05). LV
      Can impedance correlated well with LA pressure (r(2)=0.73), while RV-Can and
      RVcoil-Can were weakly correlated (r(2)=0.43 and r(2)=0.52, respectively).
      Changes in LV-RV and LV-RA impedances were also larger than those of RVcoil-Can
      and RA-Can (P0.05). Meanwhile, all impedances were associated with circadian
      variability at baseline (5+/-2%) which diminished during CHF (2+/-1%); P=0.02.
      Furthermore, significant variations were observed in cardiogenic impedances
      during progression into CHF as evidenced by reduced peak-to-peak amplitude and
      increased fractionation of the signals. CONCLUSIONS: All impedance vectors
      decreased during CHF. Impedance measurement employing left heart sensors
      correlated well wit- - h LA pressure, and may improve detection of CHF onset
      compared to sensing by RA or RV leads alone. This approach has important clinical
      implications for managing heart failure patients in the ambulatory setting.

PMID- 19164004
TI  - Theoretical possibility of ventricular fibrillation during use of TASER
      neuromuscular incapacitation devices.
AB  - INTRODUCTION: TASER devices deliver electrical pulses that temporarily
      incapacitate suspects. This study analyzes the theoretical possibility of
      ventricular fibrillation (VF) induction by TASER currents. METHODS AND RESULTS:
      Using finite element models (FEM), the results found that the skin, fat and
      anisotropic skeletal muscle layers attenuated a large portion of TASER currents,
      allowing just a fractional amount to penetrate transversally into deeper layers
      of tissue. The TASER current density reached 91 mA/cm(2), the threshold required
      to induce VF, at less than 14.7 mm away from the skin surface. This distance is
      significantly lower than the average skin-heart distance of 35 mm, as measured in
      subjects with a body-mass index (BMI) matched to that of typical in-custody
      suspects. The theoretical probability of inducing VF is significantly lower than
      0.0000008, or 1:1,270,000. By comparison, the standard for basic safety and
      essential performance of medical electrical equipment, EN 60601-1, accepts as
      satisfactory a VF induction probability of 0.002, or 1:500. CONCLUSION: The
      results indicated that TASER devices, while not risk free, have a very low
      cardiac risk profile when used for suspect temporary incapacitation.

PMID- 19164005
TI  - Coil design considerations for deep-brain transcranial magnetic stimulation
      (dTMS).
AB  - Deep-brain transcranial magnetic stimulation (dTMS) could provide new, non
      invasive therapeutic options for various psychiatric and neurological disorders.
      Figures of merit (FoMs) are proposed to evaluate and compare dTMS coil designs.
      These FoMs characterize the depth of electric field penetration, scalp
      stimulation, focality, and energy. Two coil configurations potentially suitable
      for dTMS are analyzed: circular crown coil and C-core coil. These coils have
      significantly less attenuation of the electric field strength in depth, compared
      to conventional TMS coils. In the limiting case as the coil dimensions become
      large relative to the head, the electric field decay in depth becomes linear,
      which indicates that, at best, the electric field attenuation is directly
      proportional to the depth of the target. The charge density and heating induced
      in the brain are at safe levels, but the risk of unintended neuromodulation and
      seizures with dTMS has to be evaluated further. Preliminary simulation results
      suggest that the crown coil has the best overall performance for dTMS. Finally,
      synchronous firing of all TMS coil elements appears more effective at stimulating
      deep neurons than is sequential firing.

PMID- 19164006
TI  - The effect of GSM-like ELF radiation on the alpha band of the human resting EEG.
AB  - Mobile phone handsets such as those operating in the GSM network emit extremely
      low frequency electromagnetic fields ranging from DC to at least 40 kHz. As a
      subpart of an extended protocol, the influence of these fields on the human
      resting EEG has been investigated in a fully counter balanced, double blind,
      cross-over design study that recruited 72 healthy volunteers. A decrease in the
      alpha frequency band was observed during the 20 minutes of ELF exposure in the
      exposed hemisphere only. This result suggests that ELF fields as emitted from GSM
      handsets during the DTX mode may have an effect on the resting alpha band of the
      human EEG.

PMID- 19164007
TI  - The effect of subcutaneous fat thickness on the efficacy of transcutaneous
      electrical stimulation.
AB  - Transcutaneous electrical stimulation is a widely used technique to relieve the
      symptoms of various neuromuscular disorders and to improve muscle strength. It is
      currently being investigated in the treatment of obesity to physically enable and
      encourage increased levels of voluntary exercise. Due to the high resistivity of
      subcutaneous fat tissue, higher stimulus currents are required to evoke muscle
      contraction in obese subjects than in subjects of a healthy weight, which can
      lead to patient discomfort. In this study, a three-dimensional finite element
      model of the human thigh, including skin, fat, muscle and bone, was developed to
      examine the relationship between fat thickness and evoked muscle activation. The
      effects of fat thickness, electrode size and inter-electrode distance on the
      activating function were investigated during monopolar and bipolar stimulation.
      The amplitude of the activating function was found to reduce as electrode size
      increased, however, this effect was relatively less at higher fat thicknesses.
      The activating function was also less sensitive to inter-electrode distance as
      fat thickness increased. These results indicate that by increasing electrode
      size, the current density at the skin surface can be reduced, thereby reducing
      patient discomfort while maintaining the efficacy of the electrical stimulation
      in obese patient populations.

PMID- 19164008
TI  - Smoothing blemished gene expression microarray data via missing value imputation.
AB  - Gene expression microarray technology has enabled advanced biological and medical
      research, but the data are well-recognized noisy and must be used with caution,
      since they are greatly affected by many experimental factors such as RNA
      concentration, spot typing, hybridization condition, and image analysis. It is
      highly desirable that the inaccurate data entries ('stains') can be identified
      and subsequently curated. In this paper, we propose a novel computational method,
      based on feature gene selection and sample classification, to efficiently
      discover the stains and apply imputation methods to estimate their values.
      Extensive experimental results on three Affymetrix platforms for human cancer
      diagnosis showed that by picking only 1-4% data entries as the most likely
      stains, the smoothed datasets could be used for better downstream data analyses
      such as robust biomarker identification and disease diagnosis.

PMID- 19164009
TI  - Minimum number of genes for microarray feature selection.
AB  - A fundamental problem in microarray analysis is to identify relevant genes from
      large amounts of expression data. Feature selection aims at identifying a subset
      of features for building robust learning models. However, finding the optimal
      number of features is a challenging problem, as it is a trade off between
      information loss when pruning excessively and noise increase when pruning is too
      weak. This paper presents a novel representation of genes as strings of bits and
      a method which automatically selects the minimum number of genes to reach a good
      classification accuracy on the training set. Our method first eliminates
      redundant features, which do not add further information for classification, then
      it exploits a set covering algorithm. Preliminary experimental results on public
      datasets confirm the intuition of the proposed method leading to high
      classification accuracy.

PMID- 19164010
TI  - Network motif-based identification of breast cancer susceptibility genes.
AB  - Identifying breast cancer susceptibility genes is one of the key challenges in
      breast cancer research. Conventional gene-based approaches can identify patterns
      of gene activity that sub-classify tumors, by which genes with known breast
      cancer mutations are typically not detected. In this study, we present a novel
      network motif-based approach that integrates biological network topology and high
      throughput gene expression data to identify markers not as individual genes but
      as network motifs. We observed that the network motifs are more reproducible than
      individual marker genes selected without biological network information, and that
      they achieve higher accuracy in the classification of metastatic versus non
      metastatic tumors.

PMID- 19164011
TI  - Integration of gene expression and gene copy number variations with independent
      component analysis.
AB  - It is recognized that a biological system should be characterized with multiscale
      and multi-modality imaging platforms such as using microarray gene expression and
      array CGH. While microarray gene expression analysis presents functional
      information, the array CGH analysis provides structural variations of genome
      using gene copy number analysis. The integration of this complementary
      information is challenging. We view the gene expression and copy number
      variations as two different measurements of a biological system and apply the
      independent component analysis (ICA) to project the data into statistically
      independent biological processes, which are then integrated to identify variation
      patterns in two inputs. We apply the method to cluster group of genes, resulting
      better identification of genes that are statistically significant in both
      measurements (e.g., gene expression and aCGH). We also compared the approach with
      other approaches such as principal component analysis (PCA), and generalized
      singular value decomposition (GSVD), demonstrating improved performance in 'gene
      shaving'.

PMID- 19164012
TI  - Toward a measure of classification complexity in gene expression signatures.
AB  - Gene expression signatures identify important genes that predict a specified
      outcome. In several notable diseases such as leukemia and breast cancer, the
      results have been encouraging. In these datasets, many techniques work well when
      discriminating particular outcomes. However, these same methods, applied to other
      datasets, are unable to achieve similar levels of success. Given the small sample
      sizes common to these studies and the large dimensionality of the data, several
      key issues exist when attempting to construct reliable, reproducible gene
      signatures. The classifiers may not be sufficient to discriminate classes, or the
      data itself may not be sufficient to produce effective separation. In this paper,
      three simple measures of classification complexity are considered to explore a
      limit to the predictive accuracy that can be achieved in a dataset. Two
      independent gene expression datasets (lung and colorectal cancer) are considered,
      using three different outcomes on each dataset. Four different classifiers, using
      the t-test for feature selection, were tested on these datasets as a
      representative panel of classifiers. Our results indicate that Fisher's
      discriminant ratio provides a good measure of the complexity of the
      classification problem, with a high correlation between complexity and best
      classification accuracy across all problems (R(2)=0.78). Specifically, predicting
      gender is a low complexity problem as indicated both by the complexity measure
      and the classification results. More clinically-oriented endpoints are more
      complex and have lower classification accuracies. Therefore, classification
      complexity can be used to estimate maximum attainable accuracy for a problem
      reducing the need to evaluate many different classifiers.

PMID- 19164013
TI  - Adaptive threshold to detect biologically meaningful changes in microarray data.
AB  - To detect changes in gene expression data from DNA microarrays, a fixed threshold
      value is widely used. However, it is not always guaranteed that a threshold value
      which is appropriate for highly expressed genes is suitable for genes with low
      expression. In this study, aiming at detecting biologically meaningful changes
      from a wide range of expression levels, we proposed an adaptive threshold method.
      The performance of the proposed method was investigated using publicly available
      expression data.

PMID- 19164014
TI  - Analysis of spontaneous MEG activity in Alzheimer's disease using time-frequency
      parameters.
AB  - The aim of this study was to explore the ability of several time-frequency
      parameters to discriminate between spontaneous magnetoencephalographic (MEG)
      oscillations from 20 Alzheimer's disease (AD) patients and 21 controls. The
      spectral crest factor (SCF) and the spectral turbulence (ST) were calculated from
      the time-frequency distribution of the normalized power spectral density averaged
      over all MEG sensors. Results revealed statistically significant higher SCF and
      ST mean values for AD patients than controls (p 0.05). This fact suggests a
      significant decrease in irregularity of AD patients' MEG activity. The standard
      deviation of SCF also provided significant differences (p 0.05). This result
      indicates that AD patients showed a significantly higher variability than
      controls. The highest accuracy of 85.4% (90.5% sensitivity, 80.0% specificity)
      was achieved using simultaneously the mean value and the standard deviation of
      the SCF. We conclude that the variability of the spectral parameters can yield
      complementary information to the mean values, useful to help in AD detection.

PMID- 19164015
TI  - Effects of mental fatigue on 8-13Hz brain activity in people with spinal cord
      injury.
AB  - Brain computer interfaces (BCIs) can be implemented into assistive technologies
      to provide 'hands-free' control for the severely disabled. BCIs utilise voluntary
      changes in one's brain activity as a control mechanism to control devices in the
      person's immediate environment. Performance of BCIs could be adversely affected
      by negative physiological conditions such as fatigue and altered
      electrophysiology commonly seen in spinal cord injury (SCI). This study examined
      the effects of mental fatigue from an increase in cognitive demand on the brain
      activity of those with SCI. Results show a trend of increased alpha (8-13Hz)
      activity in able-bodied controls after completing a set of cognitive tasks.
      Conversely, the SCI group showed a decrease in alpha activity due to mental
      fatigue. Results suggest that the brain activity of SCI persons are altered in
      its mechanism to adjust to mental fatigue. These altered brain conditions need to
      be addressed when using BCIs in clinical populations such as SCI. The findings
      have implications for the improvement of BCI technology.

PMID- 19164016
TI  - A watermarking algorithm for polysomnography data.
AB  - A blind watermarking algorithm for polysomnography (PSG) data in European Data
      Format (EDF) has been developed for the identification and attribution of shared
      data. This is accomplished by hiding a unique identifier in the phase spectrum of
      each PSG epoch using an undisclosed key so that a third party cannot retrieve the
      watermark without knowledge of the key. A pattern discovery algorithm is
      developed to find the watermark pattern even though the data may have been
      altered. The method is evaluated using 25 PSG studies from the Sleep Heart Health
      Study database. The integrity of the signal data was determined using time series
      measures of both the original and watermarked signals, and by determining its
      effect on scoring sleep stages from the PSG data. The results of the analysis
      indicate that the proposed watermarking method for PSG data is an effective and
      efficient way to identify shared data without compromising its intended use.

PMID- 19164017
TI  - Identifying rhythms of subthalamic neural oscillations in time-frequency domain.
AB  - We aimed to identify neural oscillations in the time-frequency representation of
      local field potentials recorded from the subthalamic nucleus. The time-frequency
      representation was normalised over the global mean and standard deviation global
      normalisation, or against the baseline period at each frequency, local
      normalisation. The cross-correlation between beta and gamma oscillations was
      enhanced by global normalisation. Furthermore, voluntary movement related
      amplitude changes in the gamma band and frequency modulation in the beta band
      were revealed by local normalisation. Thus global or local normalisation of time
      frequency representation provides a reliable and effective way to identify
      oscillatory rhythms in subthalamic neural activity by reducing noise and
      increasing frequency discrimination. It can be used to enhance the detection of
      obscure or hidden neural oscillations and improve the sensitivity of post-hoc
      analysis.

PMID- 19164018
TI  - Harmonic Golay coded excitation based on harmonic quadrature demodulation method.
AB  - Harmonic coded excitation techniques have been used to increase SNR of harmonic
      imaging with limited peak voltage. Harmonic Golay coded excitation, in
      particular, generates each scan line using four transmit-receive cycles, unlike
      conventional Golay coded excitation method, thus resulting in low frame rates. In
      this paper we propose a method of increasing the frame rate of said method
      without impacting the image quality. The proposed method performs two transmit
      receive cycles using QPSK code to ensure that the harmonic components of incoming
      signals are Golay coded and uses harmonic quadrature demodulation to extract
      compressed second harmonic component only. The proposed method has been validated
      through mathematical analysis and MATLAB simulation, and has been verified to
      yield a limited error of -52.08dB compared to the ideal case. Therefore, the
      proposed method doubles the frame rate compared to the existing harmonic Golay
      coded excitation method without significantly deteriorating the image quality.

PMID- 19164019
TI  - Spectral validation improves frequency tracking obtained by time-frequency
      analysis during atrial fibrillation.
AB  - The fibrillatory frequency trend and the time-dependent spectral characteristics
      can be investigated using a spectral profile technique in patients with atrial
      fibrillation (AF). The aim of this study is to develop model-based means for
      stricter control on the update of the spectral profile. A spectral model defined
      by Gaussian functions is suggested for describing the fundamental and harmonics
      of the atrial waves during AF, thereby accounting for basic characteristics of
      the typical AF spectrum. The model parameters are obtained from weighted least
      squares fitting of the model to the observed spectrum. The method was tested on
      simulated signals with two different frequency trends. A marked improvement was
      observed when tracking the main fibrillatory frequency as the error was reduced
      by more than 50% in comparison with the original method.

PMID- 19164020
TI  - An impulse based sensor for medical sensing applications.
AB  - This work designs a non-coherent impulse basedtransceiver operating in a
      frequency range of 3.1-10.6 GHz for medical sensing applications. The transmitter
      consists of an ON/OFF Keying data modulator, a Gaussian pulse generator, and a
      variable gain amplifier to control the transmitting pulse level. The receiver
      consists of an LNA, a multiplier, an integrator, and a comparator. The IC is
      designed using 0.18 microm CMOS technology with a supply voltage of 1.8 V. The
      simulated pulse width is 0.2 ns and the maximum pulse rate is over 1 GHz. A heart
      motion detection performance was demonstrated with high precision for an overall
      power consumption of 40 mW. This design can also be modified to be used in
      wireless UWB data communications to build a complete low power wireless sensor
      node.

PMID- 19164021
TI  - Wearable technology for bio-chemical analysis of body fluids during exercise.
AB  - This paper details the development of a textile based fluid handling system with
      integrated wireless biochemical sensors. Such research represents a new
      advancement in the area of wearable technologies. The system contains pH, sodium
      and conductivity sensors. It has been demonstrated during on-body trials that the
      pH sensor has close agreement with measurements obtained using a reference pH
      probe. Initial investigations into the sodium and conductivity sensors have shown
      their suitability for integration into the wearable system. It is thought that
      applications exist in personal health and sports performance and training.

PMID- 19164023
TI  - Flexible glucose sensor utilizing multilayer PDMS process.
AB  - In this paper, a flexible glucose sensor with gold electrodes sandwiched between
      two polydimethyle siloxane (PDMS) layers is presented. PDMS is used as a flexible
      and bio-compatible sensor substrate material. Furthermore, PDMS is optically
      transparent and haemocompatible which is very important for implantable sensors.

PMID- 19164022
TI  - Feedback control of a DNA molecule tethered in a nanopore to repeatedly probe DNA
      binding enzymes.
AB  - This paper demonstrates feedback voltage control of a single DNA molecule
      tethered in a biological nanopore. The nanopore device monitors ionic current
      through a single protein pore inserted in a lipid bilayer. The limiting aperture
      of the pore is just sufficient (1.5 nm diameter) to accommodate single-stranded
      DNA. The tethered DNA is double stranded on each end, with a single stranded
      segment that traverses the pore. Voltage control is used to regulate the motion
      of the tethered DNA, for repeated capture and subsequent voltage-promoted
      dissociation of DNA-binding enzymes above the nanopore. In initial experiments
      using the Klenow fragment of Escherichia coli DNA polymerase I, control of 8
      independent tethered DNA molecules yielded 337 dissociation events in a period of
      380 seconds. The resulting distribution of DNA-protein dissociation times can be
      used to model the free energy profile of dissociation. Moreover, the approach is
      applicable to numerous enzymes that bind or modify DNA or RNA including
      exonucleases, kinases, and other polymerases.

PMID- 19164024
TI  - Simultaneous measurement of nonlinearity and electrochemical impedance for
      protein sensing using two-tone excitation.
AB  - Impedance biosensors detect the binding of a target to an immobilized probe by
      quantifying changes in the impedance of the electrode-electrolyte interface. The
      interface's I-V relationship is inherently nonlinear, varying with DC bias, and
      target binding can alter the degree of nonlinearity. We propose and demonstrate a
      method to simultaneously measure the nonlinearity and conventional small-signal
      impedance using intermodulation products from a two-tone input. Intermodulation
      amplitudes accurately reflect the impedance's manually-measured voltage
      dependence. We demonstrate that changes in nonlinearity can discriminate protein
      binding. Our measurements suggest that target binding can alter nonlinearity via
      the voltage dependence of the ionic double layer.

PMID- 19164025
TI  - Surface plasmon resonance biochip based on ZnO thin film for nitric oxide
      sensing.
AB  - In this study, the design of a novel optical sensor that comprises surface
      plasmon resonance sensing chip and zinc oxide nano-film was proposed for the
      detection of nitric oxide gas. The electrical and optical properties of zinc
      oxide film vary in the presence of nitric oxide. This effect was utilized to
      prepare biochemical sensors with transduction based on surface plasmon resonance.
      Due to the refractive index of the transparent zinc oxide film that was deposited
      on the gold film, however, changes will be observed in the surface plasmon
      resonance spectra. For this reason, the thickness of zinc oxide film will be
      investigated and determined in this study. The interaction of nitric oxide with a
      20 nm zinc oxide layer on gold leads to the shift of the resonance angle. The
      analysis on the reflectance intensity of light demonstrates that such effect is
      caused by the variation of conductivity and permittivity of zinc oxide film.
      Finally, a shift in surface plasmon resonance angle was measured in 25 ppm nitric
      oxide at 180 C and a calibration curve of nitride oxide concentration versus
      response intensity was successfully obtained in the range of 250 to 1000 ppm
      nitric oxide at lower temperature of 150 C. Moreover, these effects are quasi
      reversible.

PMID- 19164026
TI  - High resolution reduced-FOV diffusion tensor imaging of the human pons with multi
      shot variable density spiral at 3T.
AB  - Diffusion Tensor Imaging (DTI) of localized anatomical regions (i.e brainstem,
      cervical spinal cord, and optic nerve) is challenging because of the existence of
      significant susceptibility differences in the surrounding tissues, their high
      motion sensitivity and the need for high spatial resolution to resolve the
      underlying complex histoarchitecture. The aim of the present methodology is to
      achieve high resolution DTI with motion compensating capability in localized
      regions of the central nervous system. We accomplish this by implementing self
      navigated multi-shot variable density spiral encoding with outer volume
      suppression. In vivo application of the technique on the human brainstem
      demonstrates a clear delineation of the multiple local neural tracts. We also
      investigate the partial volume effect on the extracted diffusion anisotropy
      metrics by varying the in-plane resolution while maintaining a constant signal-to
      noise ratio.

PMID- 19164027
TI  - Evaluation tests for eye tracking systems.
AB  - In this paper, we describe the tests developed by our research team to evaluate
      the performance of eye tracking algorithms to quantify vertical and horizontal
      eye movements. To perform the tests, we created a special library to generate
      synthetic eye images, where we can control most characteristics of the eyes. It
      is possible to simulate the different situations observed during the acquisition
      of eye images of a real subject.

PMID- 19164028
TI  - Magnetic resonance described in the excitation dependent rotating frame of
      reference.
AB  - An excitation dependent rotating frame of reference to observe the magnetic
      resonance phenomenon is introduced in this paper that, to the best of our
      knowledge, has not been used previously in the nuclear magnetic resonance
      context. The mathematical framework for this new rotating frame of reference is
      presented based on time scaling the Bloch equation after transformation to the
      classical rotating frame of reference whose transverse plane is rotating at the
      Larmor frequency. To this end, the Bloch equation is rewritten in terms of a
      magnetisation vector observed from the excitation dependent rotating frame of
      reference. The resultant Bloch equation is referred to as the time scaled Bloch
      equation. In the excitation dependent rotating frame of reference whose
      coordinates are rotating at the instantaneous Rabi frequency the observed
      magnetisation vector is a much slower signal than the true magnetisation in the
      rotating frame of reference. As a result the ordinary differential equation
      solvers have the ability to solve the time scaled version of the Bloch equation
      with a larger step size resulting in a smaller number of samples for solving the
      equation to a desired level of accuracy. The simulation results for different
      types of excitation are presented in this paper. This method may be used in true
      Bloch simulators in order to reduce the simulation time or increase the accuracy
      of the numerical solution. Moreover, the time scaled Bloch equation may be
      employed to determine the optimal excitation pattern in magnetic resonance
      imaging as well as designing pulses with better slice selectivity which is an
      active area of research in this field.

PMID- 19164029
TI  - Minimal-SAR RF pulse optimization for parallel transmission in MRI.
AB  - Parallel transmission is an emerging technique to achieve multi-dimensional
      spatially selective or modulated excitation in Magnetic Resonance Imaging (MRI).
      Minimizing Specific Absorption Ratio (SAR) is a critical issue in this technique
      for radio frequency power absorption safety. In this paper, we presented an
      automatic design method to minimize SAR in an optimization framework. The RF
      pulses and corresponding k-space trajectory are iteratively adjusted. The method
      is verified using computer simulations of a 4-channel parallel transmission
      system. The results showed significantly reduction in SAR can be achieved while
      the quality of the excited pattern is well preserved without enlonging the pulse
      duration.

PMID- 19164030
TI  - Is undiagnosed synaesthesia a confounding factor in the interpretation of MRI
      images?
AB  - Synaesthesia is a condition in which stimulation of a sensory modality evokes
      another sensation in the same or a different sensory modality. Currently,
      synaesthesia is considered a neurological condition that involves crosstalk
      between brain regions. Given the numerous anatomical and functional connections
      within the brain, it is possible that undiagnosed synaesthesia may influence the
      results of functional magnetic resonance imaging (fMRI) studies or even
      structural MRI. In this paper, we investigated the currently available literature
      to determine if and how the sensations invoked by synaesthesia could impact fMRI
      and structural MRI. Our investigation found that synaesthesia can have a profound
      impact on fMRI studies of sensory and cognitive functions, and there is evidence
      to suggest structural connections in the brain are also altered. Given the low
      prevalence of synaesthesia, the likelihood of synaesthesia being a confounding
      factor in fMRI studies of patient groups is small; however, determining the
      presence of synaesthesia is important for investigating individual patients.

PMID- 19164031
TI  - Multi-divergent-beam stationary cardiac SPECT.
AB  - Multi-pinhole SPECT (single photon emission computed tomography) is widely used
      in small animal imaging. Recently multi-pinhole SPECT has been applied to human
      cardiac imaging, and it has been shown that if three SPECT cameras are used, the
      multi-pinhole system can be stationary. A stationary cardiac SPECT system forces
      the pinholes to operate at image reduction mode, where the object must be
      positioned away from the pinholes. With this imaging reduction mode setup, the
      divergent-beam collimator provides better sensitivity than the pinhole collimator
      when they have the same image reduction factor and the same spatial resolution.
      This paper suggests for a stationary cardiac SPECT system to use the multi
      divergent-hole collimators instead of the multi-pinhole collimators.

PMID- 19164032
TI  - Electrical endogenous heating of insect muscles for flight control.
AB  - In our ongoing effort to reliably control insect flight with pupae-inserted
      electronics, we demonstrate using heat to control insect flight initiation or
      take-off from standing position. We have previously developed reliable surgical
      methods to implant neuromuscular prosthetic devices in insect flight muscle for
      directing flight electrically. Here, we present, for the first time, a tissue
      embedded micro heater to decrease the preflight warm-up duration of hybrid
      electronic insect micro-air-vehicles. The biological takeoff-time at room
      temperature of 5-10 minutes was reduced to 58- seconds by thorax heating.
      Minimization of takeoff-time will enable higher bandwidth and reliable control
      for repeated takeoff and landing applications.

PMID- 19164033
TI  - Intraocular epiretinal prosthesis to restore vision in blind humans.
AB  - Visual sensations in blind patients suffering from retinal degenerations may be
      restored by electrical stimulation of retinal neurons using implantable
      microelectrode arrays. The EPI-RET-3 project was initiated to evaluate a wireless
      intraocular retinal implant system for human use in terms of safety and
      efficiency. The implant is a remotely controlled fully intraocular prosthesis
      consisting of a receiver and a stimulator module. The stimulator is placed onto
      the retina's surface. Data and energy are transmitted via an inductive link from
      outside the eye to the implant. The EPI-RET-3 device was implanted into six
      legally blind patients with Retinitis Pigmentosa (RP) for a period of four weeks.
      The surgery was performed without complications. The implants were activated on
      days 7, 14 and 27 after implantation. All patients reported visual sensations
      such as dots, arcs, or lines of different colours and intensities. The required
      stimulation thresholds were found to be very low. Implantation of the wireless
      EPI-RET-3 device is safe and the system is suitable to elicit visual sensations
      in blind RP patients. Major problems in the design and fabrication of a
      prosthesis for artificial vision could be solved in this approach.

PMID- 19164034
TI  - Cortical recording with polypyrrole microwire electrodes.
AB  - The ability to record from the same neuron for extended periods of time is
      essential to understanding how the brain reorganizes during learning.
      Conventional chronic recording microelectrodes are made from metal or silicon.
      However, the large stiffness mismatch between the electrodes and brain tissue
      causes shear-induced inflammation, limiting long-term recording stability. The
      flexibility of polypyrrole microwire has the potential to improve the chronic
      recording stability by minimizing the stiffness mismatch. In this paper, we
      report the implantation of a conducting polymer microwire electrode in a rodent
      brain, and the successful recording of cortical activity using such an electrode.

PMID- 19164035
TI  - A 3D slim-base probe array for in vivo recorded neuron activity.
AB  - This paper introduces the first experimental results of a new implantable slim
      base three-dimensional (3D) probe array for cerebral applications. The probes are
      assembled perpendicularly into the slim-base readout platform where electrical
      and mechanical connections are achieved simultaneously. A new type of
      micromachined interconnect has been developed to establish electrical connection
      using extreme planarization techniques. Due to the modular approach of the
      platform, probe arrays of different dimensions and functionality can be
      assembled. The platform is only several hundred microns thick which is highly
      relevant for chronic experiments in which the probe array should be able to float
      on top of the brain. Preliminary tests were carried out with the implantation of
      a probe array into the auditory cortex of a rat.

PMID- 19164036
TI  - A photosensitive polyimide based method for an easy fabrication of multichannel
      neural electrodes.
AB  - To develop practical and inexpensive multichannel neural electrodes, we designed
      and fabricated photosensitive polyimide based flexible multichannel neural
      electrodes using MEMS technologies. Compared to a conventional micromachining
      with non-photosensitive materials, the advantage of applying photosensitive
      polyimide is the elimination of the dry etching, which involves the complex
      multilevel processes for controlling the etching conditions to define the outline
      of the neural electrodes and expose the microelectrodes. Thus, photosensitive
      polyimide allows more options in optimization of the configuration and size of
      neural electrodes depending on experimental purposes, and enables fabrication at
      a lower cost with improvement of process yields.

PMID- 19164037
TI  - A compact architecture for three-dimensional neural microelectrode arrays.
AB  - A new architecture is presented for achieving three-dimensional electronic
      interfaces to the nervous system using planar microfabricated two-dimensional
      arrays. This architecture overcomes many of the limitations of existing
      approaches and enables flexible electrode configurations with minimal overhead in
      size. A 64-channel (4x4x4) 3-D array using this architecture is demonstrated with
      sites on 100 microm centers, interfacing with a volume of tissue less than
      0.1mm3. The 1mm2 footprint of the device is the smallest ever reported.

PMID- 19164038
TI  - Hypnotic administration for anesthesia using sliding-mode control.
AB  - Nowadays general anesthesia is maintained using as the controller the human
      intervention, relying only on the quick and certain response of the
      anesthesiologist to the surrounding conditions, in order to provide the adequate
      state of anesthesia for the three main components - hypnosis, analgesia and
      paralysis. One of the most advantageous breakthroughs in anesthesia has been the
      appearance of depth of anesthesia monitors, assisting anesthesiologists in the
      hard job of knowing the hypnotic state of a patient. This information allows a
      way of closing the loop for administration of the hypnotic drug, and a more
      secure maintenance of hypnosis. The objective of this work was to apply sliding
      mode control techniques to the model structure of the hypnotic in the human body
      (measured by the effect), and evaluate the robustness of this method to expected
      deviations from the average patient.

PMID- 19164039
TI  - A neuro-fuzzy approach for predicting hemodynamic responses during anesthesia.
AB  - The effect of drugs' interaction on the hemo-dynamic variables is of great
      importance when considering patient's safety and stability. It is also important
      for control infusion systems during anesthesia. In this article, an adaptive
      network fuzzy inference system is used to model the effect of two drugs (propofol
      and remifentanil) on the mean arterial pressure and heart rate. The clinical data
      of 45 patients is used to train and test the model. The use of subtractive
      clustering improved the model performance on the testing data set. The fuzzy
      model is able to capture the synergistic interaction between the two drugs, but
      other influences were detected.

PMID- 19164040
TI  - Target controlled infusion for kids: trials and simulations.
AB  - Target controlled infusion (TCI) for Kids is a computer controlled system
      designed to administer propofol for general anesthesia. A controller establishes
      infusion rates required to achieve a specified concentration at the drug's effect
      site (C(e)) by implementing a continuously updated pharmacokinetic
      pharmacodymanic model. This manuscript provides an overview of the system's
      design, preclinical tests, and a clinical pilot study. In pre-clinical tests,
      predicted infusion rates for 20 simulated procedures displayed complete
      convergent validity between two software implementations, Labview and Matlab, at
      computational intervals of 5, 10, and 15s, but diverged with 20s intervals due to
      system rounding errors. The volume of drug delivered by the TCI system also
      displayed convergent validity with Tivatrainer, a widely used TCI simulation
      software. Further tests, were conducted for 50 random procedures to evaluate
      discrepancies between volumes reported and those actually delivered by the
      system. Accuracies were within clinically acceptable ranges and normally
      distributed with a mean of 0.08 +/- 0.01 ml. In the clinical study, propofol
      pharmacokinetics were simulated for 30 surgical procedures involving children
      aged 3 months to 9 years. Predicted C(e) values during standard clinical
      practice, the accuracy of wake-up times predicted by the system, and potential
      correlations between patient wake-up times, C(e), and state entropy (SE) were
      assessed. Neither Ce nor SE was a reliable predictor of wake-up time in children,
      but the small sample size of this study does not fully accommodate the noted
      variation in children's response to propofol. A C(e) value of 1.9 mug/ml was
      found to best predict emergence from anesthesia in children.

PMID- 19164041
TI  - Model predictive control of depth of anaesthesia: guidelines for controller
      configuration.
AB  - The paper presents a feasibility study on the use of Model based Predictive
      control (MPC) to regulate the level of Depth of Anaesthesia (DoA) when measured
      by the BIS index. Pharmacokinetic/pharmacodynamic nonlinear models of DoA when
      Propofol and Remifentanil are used as hypnotic and analgesic drugs are linearized
      around the desired working point for DoA in order to obtain a linear state-space
      model coupled with an extra integrator to include integral action in the control.
      This state-space model is then used in a MPC algorithm. The main contribution of
      the paper consists in the characterization of the influence of the different
      design parameters in the MPC performance when controlling DoA.

PMID- 19164042
TI  - Personalized neuromuscular blockade through control: clinical and technical
      evaluation.
AB  - This paper presents a statistical analysis of clinical data collected in
      surgeries under automatic closed-loop control of neuromuscular blockade. Four
      different control strategies have been applied in patients undergoing elective
      surgeries and clinical and technical evaluations of the control system were
      performed. Both transient and steady-state behaviour were analysed in detail and
      clearly suggest an automatic control approach relying on the information about
      the patient dynamics. The results can be a valuable start point to design
      personalized drug infusion control in anaesthesia.

PMID- 19164043
TI  - Electrical conductivity imaging of lower extremities using MREIT: postmortem
      swine and in vivo human experiments.
AB  - Cross-sectional conductivity images of lower extremities were reconstructed using
      Magnetic Resonance Electrical Impedance Tomography (MREIT) techniques. Carbon
      hydrogel electrodes were adopted for postmortem swine and in vivo human imaging
      experiments. Due to their large surface areas and good contacts on the skin, we
      could inject as much as 10 mA into the lower extremities of human subjects
      without producing a painful sensation. Using a 3T MREIT system, we first
      performed a series of postmortem swine experiments and produced high-resolution
      conductivity images of swine legs. Validating the experimental protocol for the
      lower extremities, we revised it for the following human experiments. After the
      review of the Institutional Review Board (IRB), we conducted our first MREIT
      experiments of human subjects using the same 3T MREIT system. Collecting magnetic
      flux density data inside lower extremities subject to multiple injection
      currents, we reconstructed cross-sectional conductivity images using the harmonic
      B(z) algorithm. The conductivity images very well distinguished different parts
      of muscles inside the lower extremities. The outermost fatty layer was clearly
      shown in each conductivity image. We could observe severe noise in the outer
      layer of the bones primarily due to the MR signal void phenomenon there.
      Reconstructed conductivity images indicated that the internal regions of the
      bones have relatively high conductivity values. Future study is desired in terms
      of the conductivity image reconstruction algorithm to improve the image quality.
      Further human imaging experiments are planned and being conducted to produce high
      resolution conductivity images from different parts of the human body.

PMID- 19164044
TI  - Acoustic vector tomography and its application to magnetoacoustic tomography with
      magnetic induction (MAT-MI).
AB  - A new tomographic algorithm for reconstructing a curl-free vector field, whose
      divergence serves as acoustic source is proposed. It is shown that under certain
      conditions, the scalar acoustic measurements obtained from a surface enclosing
      the source area can be vectorized according to the known measurement geometry and
      then be used to reconstruct the vector field. The proposed method is validated by
      numerical experiments. This method can be easily applied to magnetoacoustic
      tomography with magnetic induction (MAT-MI). A simulation study of applying this
      method to MAT-MI shows that compared to existing methods, the proposed method can
      give an accurate estimation of the induced current distribution and a better
      reconstruction of electrical conductivity within an object.

PMID- 19164045
TI  - Robust approach to skin location estimation for radar-based breast imaging
      systems.
AB  - Increasingly complex breast models are being used to test emerging microwave
      imaging modalities. With the increased complexity, waveforms received from skin
      reflections may consist of contributions from multiple locations, resulting in
      signatures not examined with simpler models. For example, antennas placed near
      the chest wall or at significant distances from the breast have been found to
      receive multiple skin reflections. With these received signals, simple methods
      used to estimate skin location, such as peak detection, do not provide reliable
      results. In this paper, we apply a deconvolution technique to find the impulse
      response with respect to a known reflected signal. Results demonstrate that this
      method provides more reliable estimates of skin location and shows the ability to
      estimate two skin locations from a waveform exhibiting two dominant skin
      reflections.

PMID- 19164046
TI  - Measurement of current density vectors in a live pig for the study of human
      electro-muscular incapacitation devices.
AB  - Current density imaging (CDI) is an MRI technique used to quantitatively measure
      current density vectors in biological tissue. A CDI sequence and corresponding
      experimental method were developed for the study of human electro-muscular
      incapacitation (HEMI) devices using an animal model. Measurements of current
      density vectors were performed in piglets weighing 4 to 5 kg. Pathways of current
      density vectors in the region of the chest and heart were investigated using
      vector plotting and streamline integration methods. Measurement of current
      density vectors were also used to analyze the relationship between applied
      current amplitude and measured current density magnitude in the range of 10 mA to
      45 mA of applied current.

PMID- 19164047
TI  - Nuadu concept for personal management of lifestyle related health risks.
AB  - Majority of the health risks and diseases in the modern world are related to
      lifestyles, e.g., overweight, unhealthy diet, physical inactivity, sleep
      deprivation, and stress. Behavioral change towards healthy lifestyles is the key
      to the prevention and management of these risks, but early and efficient
      interventions are scarcely available. We present the Nuadu Concept, an ICT
      (Information and Communication Technologies) assisted wellness toolbox for the
      management of multiple, behavior-originated health risks. The concept is based on
      psychological models, which provide methods and motivation for behavior change.
      The individual is considered as the best expert of his/her own wellness. Thus,
      the Nuadu Concept provides a variety of personal wellness technologies and
      services, among which the user may freely choose the best tools for him/herself.
      We believe this approach has the potential to provide efficient, acceptable,
      available, and affordable wellness management support for a significant number of
      people.

PMID- 19164048
TI  - Design evaluation of a home-based telecare system for Chronic Heart Failure
      patients.
AB  - In order to improve the care of Chronic Heart Failure (CHF) patients, a system
      has been developed for monitoring symptoms and document subjective judgments on
      health conditions in a home environment. Since system usability is an important
      issue, a two step evaluation of the solution was conducted. First a ten-patient
      survey was conducted, which was aimed at spotting possible problem areas. The
      second step involved a small trial in a home setting with CHF patients. The
      results are promising, indicating that the system is user friendly and easy to
      use, and that it is suitable as a prototype for the intended use.

PMID- 19164049
TI  - OURSES: a telemedicine project for rural areas in france. Telemonitoring of
      elderly people.
AB  - Several telemedicine applications are proposed within the frame of OURSES
      project, French acronym for Offer of Rural Use of Services by Satellite,
      providing services for elderly people. The main objective of this project is to
      show the interest of using satellites as a complement to terrestrial
      technologies, in areas where telecommunication infrastructure is lacking or
      incomplete. This paper describes one of these applications: an ECG monitoring
      system. This telemonitoring system allows, thanks to a wireless wearable sensor,
      to detect possible cardiac problems of elderly people. ECG signals are analyzed
      through signal processing algorithms and if some abnormal condition is detected,
      an alarm is raised and sent via satellite to the physician's office. The
      corresponding physician is able to access at any time the recorded ECG signals,
      whenever he is willing to, in the presence of an alarm or not. This allows a
      constant monitoring of the elderly people. Tests realized in a real environment
      have demonstrated the feasibility and the interest of this application.

PMID- 19164050
TI  - Experiences with fetal phonocardiographic telemonitoring and future
      possibilities.
AB  - Phonocardiography (PCG) makes possible the examination of some fetal cardiac
      anomalies which otherwise usually remain undetected during pregnancy. The
      application of PCG in a telemonitoring system enhances its diagnostic
      capabilities, allowing long-term measurements even at home. The paper summarizes
      the intensive fetal monitoring campaign carried out in Hungary during the last
      three years that yielded useful experience regarding recent and future
      possibilities of fetal monitoring. Results collected from a large number of
      measurements suggest that PCG home monitoring may be a suitable screening method
      for fetal congenital heart diseases, even if surgical intervention in this phase
      of pregnancy is not easy.

PMID- 19164051
TI  - Early experiences of the use of remote patient monitoring for the long term
      management of chronic disease.
AB  - We describe our experiences of using remote patient monitoring to support the
      long term management and clinical intervention in patients with chronic disease.
      Within the project we developed new algorithms to determine from vital signs
      collected on a daily basis, those patients requiring clinical investigation for
      their condition. Our aim was for patients to achieve and sustain clinically
      recommended values for parameters. In our study, the telemonitoring prompted
      clinical intervention in 37% of patients. Our approach proved particularly
      effective for the newly diagnosed, and for those with long term issues of
      management.

PMID- 19164052
TI  - Wearable EEG: what is it, why is it needed and what does it entail?
AB  - This paper presents a review of wearable EEG technology: the evolution of
      ambulatory EEG units from the bulky, limited lifetime devices available today to
      small devices present only on the head that can record the EEG for days, weeks or
      months at a time. The EEG requirements, application areas and research challenges
      are highlighted. A survey of neurologists is also carried out clearly indicating
      the medical desire for such devices.

PMID- 19164053
TI  - Real time workload classification from an ambulatory wireless EEG system using
      hybrid EEG electrodes.
AB  - This paper describes a compact, lightweight and ultra-low power ambulatory
      wireless EEG system based upon QUASAR's innovative noninvasive bioelectric sensor
      technologies. The sensors operate through hair without skin preparation or
      conductive gels. Mechanical isolation built into the harness permits the
      recording of high quality EEG data during ambulation. Advanced algorithms
      developed for this system permit real time classification of workload during
      subject motion. Measurements made using the EEG system during ambulation are
      presented, including results for real time classification of subject workload.

PMID- 19164054
TI  - Generic vs custom; analogue vs digital: on the implementation of an online EEG
      signal processing algorithm.
AB  - This paper quantifies the performance difference between custom and generic
      hardware algorithm implementations, illustrating the challenges that are involved
      in Body Area Network signal processing implementations. The potential use of
      analogue signal processing to improve the power performance is also demonstrated.

PMID- 19164055
TI  - A 1.2V 1.5 microW 4 kS/s 10b Pipelined ADC for electroencephalogram applications.
AB  - This paper presents the design of a Pipelined Analog-to-Digital Converter (ADC)
      for Electroencephalogram (EEG) applications with 10 bits of resolution, 1.2V of
      supply voltage and only 1.5 microW of power consumption using a standard 0.5
      microm CMOS technology. Low-voltage and low-power operation has been achieved
      using Quasi-Floating-Gate (QFG) based circuits. The use of a new class-AB
      operational amplifier in weak inversion allows very low power consumption and
      high enough open loop gain. Simulation results show an energy efficiency of 0.84
      pJ per quantization level, placing the converter into the state-of-the-art of low
      frequency low-power ADCs.

PMID- 19164056
TI  - On data reduction in EEG monitoring: comparison between ambulatory and non
      ambulatory recordings.
AB  - OBJECTIVE: To compare the performance of an EEG data selection/reduction
      algorithm for epileptic EEGs on ambulatory and non-ambulatory recorded data to
      confirm that acceptable performance is achievable in ambulatory recordings
      despite the presence of overt artifacts. METHODS: A total of 167 hours of EEG
      data containing 899 marked interictal events is analysed to determine the
      percentage of events correctly recorded (the sensitivity) and the amount of data
      reduction achieved. RESULTS: A better sensitivity-data reduction trade-off is
      found in the ambulatory recorded data. This may be unexpected as ambulatory
      recordings are known to contain large numbers of artifacts, but is accounted for
      by these artifacts being easily detected and discarded, improving the data
      reduction. CONCLUSIONS: Satisfactory performance levels are found in both data
      types, no degradation is present with ambulatory recordings. SIGNIFICANCE:
      Demonstrates that the processing of EEG data for wearable EEG applications is
      feasible without a loss in performance compared to traditional inpatient EEG
      usage.

PMID- 19164057
TI  - Measuring and evaluating ground truth for boundary detection in medical images.
AB  - In this paper we describe a methodology for measuring the ground truth for
      boundary detection methods in medical images. An interface is used to allow
      medical experts to outline boundaries of interest on images. Following this, the
      accuracy of the experts in repeating the ground truth detection process is
      evaluated. Finally, an approach is described for comparing the ground truth as
      provided by experts with actual boundaries detected automatically. Experimental
      results are presented to validate the proposed algorithms.

PMID- 19164058
TI  - 4D alignment of bidirectional dynamic MRI sequences.
AB  - Over the past decade, research in medical imaging and visualization has seen a
      progression from 2D to 3D and now 4D representation of medical data. 4D (3D
      +time) representation allows one to not only visualize a 3D structure, but also
      to study its functional movement. However, due to technological limitations no
      current acquisition modality acquires data in 4D. Instead, 4D data is created
      from multiple 3D or 2D acquisitions. In this paper we describe a method that
      spatio-temporally aligns dynamic 2D MRI sequences acquired in bidirectional,
      orthogonal planes (sagittal and coronal) for 4D visualization. As a proof of
      concept, we focus on the assessment of swallowing as a representative application
      of our work. MRI sequences with unknown temporal offsets are acquired through
      repeated instances of swallowing. We present a method that identifies common
      regions of interest (ROI) in the orthogonal sequences and combines image
      intensity profiles from the orthogonal ROIs, via registration to a fiducial
      volume, to align the MRI sequences. An interesting consequence of using
      bidirectional acquisition planes is that video sequences in the same acquisition
      view (e.g all sagittal sequences) automatically get aligned with respect to each
      other. The bidirectional alignment results are validated by comparing the sum of
      squared difference (SSD) values over all possible alignments of the sagittal
      sequences. Experimentally it is found that a minima in the SSD values corresponds
      to the alignment computed by our proposed method.

PMID- 19164059
TI  - Effects of texture and color on the perception of medical images.
AB  - Carefully and appropriately designed texture patterns, for highlighting the
      underlying geometry, in addition to standard shading and simulated lighting, can
      enhance the perception of 3D surface properties such as curvature and
      orientation. In this paper we propose enhancements to a texture synthesis
      algorithm for 3D medical data visualization, incorporating a robust texture patch
      boundary handling technique. We compare different texture and color mapping
      techniques on a medical object and evaluate their effects based on feedback from
      human observers. Experimental results show the feasibility of our enhanced
      algorithm.

PMID- 19164060
TI  - Effects of vibratory actuation on endoscopic capsule vision.
AB  - Current research in capsule endoscopy aims at endowing the capsules with some
      means of actively propelling themselves inside the gastrointestinal (GO tract, as
      opposed Advantages of these active capsules are the sipificant potential in the
      duration of the associated diagnostic procedures. as well as the oossihilitv to
      direct the line-of-sieht of the oh-hoard cameras towards interesting features of
      the GI tissue. One such means of active propulsion is by vibratory actuation,
      employing eccentric-mass micromotors, which is shown to reduce the friction of
      the capsule with the GI tract. The effect of vibrations on the quality of the
      acquired images is explored in the present study, which demonstrates that such
      vibrations do not affect adversely the diagnostic effectiveness of the endoscopic
      capsules. The parameters of vibratory actuation are evaluated as to the loss bf
      high-frequency information in the acquired images, due to the induced motion
      blur, and appropriate design guidelines for the vibratory actuation system are
      established. The validity of this study has been evaluated by ex-vivo and in-vivo
      experiments.

PMID- 19164062
TI  - Assessment of the effects of increasing levels of physiological realism in the
      computational fluid dynamics analyses of implanted coronary stents.
AB  - Coronary stent implantation can improve blood flow in an artery that has been
      narrowed by the build up of arterial plaque. However, the implantation of the
      stent will change the geometry of the vessel wall. The haemodynamic effects of
      the stents presence and alteration of the vessel wall are unclear. The
      redistribution of flow induced vessel wall shear stress (WSS) and wall shear
      stress gradient (WSSG) may directly contribute to restenosis (re-blockage).
      Computational fluid dynamics (CFD) is used extensively to identify these
      parameters in stented vessels. However, simplifications to the model of the
      stented artery are common. In this paper, computational domains of stented
      arteries with increasing levels of physiological realism are created. CFD is used
      to predict the WSS and WSSG for each set of computational domains. Finally, the
      results show that certain simplifications are not valid for CFD analyses of
      implanted coronary stents.

PMID- 19164063
TI  - Efficient solutions of cardiac membrane models using novel unsupervised
      clustering algorithm.
AB  - We present a method to efficiently solve cardiac membrane models using a novel
      unsupervised clustering algorithm. The unsupervised clustering algorithm was
      designed to handle repeated clustering of multidimensional objects with rapidly
      changing properties. A Modified Trie datastructure that allowed efficient search,
      scalable and distributed assembly of the result was designed. The method was
      applied to solve monodomain models of cardiac tissue with highly non-linear
      reaction elements. We demonstrate the versatility and advantages of using the
      method by subjecting the tissue to various spatial excitation patterns.

PMID- 19164064
TI  - Models for mechanistic investigations of pacing arrthymogenesis and cardiac
      tissue structure.
AB  - Two-dimensional in silico models have been constructed for investigating
      electrical dynamics arising due to pacing rates and tissue discontinuities.
      Discontinuities (structures) are introduced explicitly through flux
      discontinuities in the intracellular space. These models use isotropic
      electrophysiological properties with heterogeneity arising solely from tissue
      structure. Both simplified and tissue-specific structures can be used together
      with membrane models with varying restitution properties. Stimuli are delivered
      at increasing pacing rates, and solution restarts enable the investigation of
      repeat stimulation at any of the rates. Investigations using these models are
      providing new insights into mechanisms leading to conduction block and
      arrhythmogenesis in cardiac tissue.

PMID- 19164066
TI  - An efficient computational method for simulation of the two-dimensional
      electrophysiological waves.
AB  - This work presents an efficient simulation for the two-dimensional bidomain
      model, a non-linear system of partial differential equations which is widely used
      for simulation of the electrical activity of the heart. The accuracy of the
      solution is obtained by using an anisotropic time-dependent adaptive method. The
      method reduces greatly the number of element and therefore the computational
      time. Two-dimensional numerical results are presented to illustrate the
      performance of the proposed method.

PMID- 19164065
TI  - A non-invasive assessment for endothelial function of small animals.
AB  - At present, many studies indicate that atherosclerosis has high correlation with
      risk factors of cardiovascular diseases. Furthermore, atherosclerosis usually
      accompanies with endothelial dysfunction. However, endothelial dysfunction dose
      not necessarily have situation of atherosclerosis. It means that endothelial
      dysfunction can be the early change of atherosclerosis. If we can use non
      invasive methods to monitor the function of vascular endothelia, it will be very
      helpful for early assessment of atherosclerosis. It can also detect
      atherosclerosis earlier then decrease the mortality and mobility of
      atherosclerosis related diseases, such as coronary artery disease, stroke and
      chronic renal disease, with appropriate management.

PMID- 19164067
TI  - Reduced conduction reserve of the propagating cardiac impulse in the diabetic rat
      heart: a model study.
AB  - Conduction velocity is dependent on two main factors: intercellular electrical
      coupling and cellular electrical excitability. There is significant redundancy,
      'conduction reserve', in these parameters such that significant reduction in the
      conduction velocity of the action potential requires either a severe change in
      one of these parameters or a combined change in both parameters. Studies in
      diabetic rat hearts have shown a significant reduction in the conduction reserve
      and it was hypothesized that this is mainly due to the lateralization of the gap
      junction protein connexin 43 (Cx43). To gain a better understanding of the effect
      of reduced intercellular coupling, a rat ventricle myocyte model was used to
      simulate propagation along a strand of cells. Simulations were performed to
      assess the effect of reduction of intercellular conductance on the conduction
      velocity. As the conductance of the gap junction decreased a significant
      reduction in the conduction velocity was observed. The relationship between
      conduction velocity and intercellular coupling became steeper with decreasing
      coupling, such that conduction velocity became increasingly sensitive to further
      uncoupling. This is consistent with experimental results, in which application of
      the gap junction uncoupler heptanol caused a larger conduction slowing in
      diabetic hearts than in controls.

PMID- 19164069
TI  - You're hired! Negotiating your first biomedical engineering position: academia
      vs. private sector.
AB  - This session is intended to prepare current bio-engineering students and post
      doctoral fellows and getting them in the right shape to apply, negotiate and
      succeed in getting their first job in industry or academia. Tips on putting
      together the appropriate CV, preparing your portfolio and getting ready for the
      interview will be covered by the invited speakers. Academia-oriented trainees
      will also get a better feel on the academic requirements, what items should be
      highlighted in the CV, what makes a well-rounded junior faculty and what the
      expectations are of junior/assistant professors.

PMID- 19164070
TI  - Women in biomedical engineering and health informatics.
AB  - A valuable session for anyone whether student or not, interested in learning more
      about Biomedical Engineering and Health Informatics as a career choice for women.
      Prominent women within the domains Biomedical Engineering and Health Informatics
      will present their research and their humanitarian interests that motivate them.
      Utilise the fantastic networking opportunity that will conclude this session to
      build and establish new professional networks with other women interested in your
      fields of expertise. Bring your contact details and be ready to make new contacts
      that are relevant for you.

PMID- 19164071
TI  - Distributed processing for features improvement in real-time portable medical
      devices.
AB  - Portable biomedical devices are being developed and incorporated in daily life.
      Nevertheless, their standalone capacity is diminished due to the lack of
      processing power required to face such duties as for example, signal artifacts
      robustness in EKG monitor devices. The following paper presents a multiprocessor
      architecture made from simple microcontrollers to provide an increase in
      processing performance, power consumption efficiency and lower cost.

PMID- 19164072
TI  - Electrocorticographic spectral changes associated with ipsilateral individual
      finger and whole hand movement.
AB  - The study of the human sensorimotor (SM) cortex activations associated with hand
      motor movement is central to the design of efficient and clinically useful brain
      computer interfaces. Whereas the electrocorticographic (ECoG) signatures of
      contralateral hand movement have been studied in detail, those of ipsilateral
      hand and individual finger movements have not been characterized. We studied the
      low (8-32 Hz) and high-frequency (76-100 Hz) SM cortical ECoG spectral changes
      associated with contralateral and ipsilateral whole hand and individual finger
      movement and assessed their discriminability. We find that ipsilateral movement
      is associated with widespread decreases in the low-frequency band (LFB) and more
      focal increases in the high-frequency band (HFB). The HFB component discriminates
      between ipsilateral and contralateral movement-associated activations, in
      contrast to the LFB. The HFB also discriminates between thumb and index finger
      movement-associated activations, for both the contralateral and the ipsilateral
      case, whereas the LFB does not. This is the first published report of a
      discriminable ipsilateral motor signal, with important implications in the use of
      brain-computer interfaces in hemiplegic patients.

PMID- 19164073
TI  - Automated quantitative assessment of HER-2/neu immunohistochemical expression in
      breast cancer.
AB  - The expression of the HER-2/neu (HER2) gene, a member of the epidermal growth
      factor receptor family, has been shown to be a valuable prognostic indicator for
      breast cancer. However, interobserver variability has been reported in the
      evaluation of HER2 with immunohistochemistry. It has been suggested that
      automated computer-based evaluation can provide a consistent and objective
      evaluation of HER2 expression. In this manuscript, we present an automated method
      for the quantitative assessment of HER2 using digital microscopy. The method
      processes microscopy images from tissue slides with a multistage algorithm,
      including steps of color pixel classification, nuclei segmentation, and cell
      membrane modeling, and extracts quantitative, continuous measures of cell
      membrane staining intensity and completeness. A minimum cluster distance
      classifier merges the features to classify the slides into HER2 categories. An
      evaluation based on agreement analysis with pathologist-derived HER2 scores,
      showed good agreement with the provided truth. Agreement varied within the
      different classes with highest agreement (up to 90%) for positive (3+) slides,
      and lowest agreement (72%-78%) for equivocal (2+) slides which contained
      ambiguous scoring. The developed automated method has the potential to be used as
      a computer aid for the immunohistochemical evaluation of HER2 expression with the
      objective of increasing observer reproducibility.

PMID- 19164074
TI  - Symmetry-based scalable lossless compression of 3D medical image data.
AB  - We propose a novel symmetry-based technique for scalable lossless compression of
      3D medical image data. The proposed method employs the 2D integer wavelet
      transform to decorrelate the data and an intraband prediction method to reduce
      the energy of the sub-bands by exploiting the anatomical symmetries typically
      present in structural medical images. A modified version of the embedded block
      coder with optimized truncation (EBCOT), tailored according to the
      characteristics of the data, encodes the residual data generated after prediction
      to provide resolution and quality scalability. Performance evaluations on a wide
      range of real 3D medical images show an average improvement of 15% in lossless
      compression ratios when compared to other state-of-the art lossless compression
      methods that also provide resolution and quality scalability including 3D
      JPEG2000, JPEG2000, and H.264/AVC intra-coding.

PMID- 19164075
TI  - MR image segmentation using a power transformation approach.
AB  - This study proposes a segmentation method for brain MR images using a
      distribution transformation approach. The method extends traditional Gaussian
      mixtures expectation-maximization segmentation to a power transformed version of
      mixed intensity distributions, which includes Gaussian mixtures as a special
      case. As MR intensities tend to exhibit non-Gaussianity due to partial volume
      effects, the proposed method is designed to fit non-Gaussian tissue intensity
      distributions. One advantage of the method is that it is intuitively appealing
      and computationally simple. To avoid performance degradation caused by intensity
      inhomogeneity, different methods for correcting bias fields were applied prior to
      image segmentation, and their correction effects on the segmentation results were
      examined in the empirical study. The partitions of brain tissues (i.e., gray and
      white matter) resulting from the method were validated and evaluated against
      manual segmentation results based on 38 real T1-weighted image volumes from the
      internet brain segmentation repository, and 18 simulated image volumes from
      BrainWeb. The Jaccard and Dice similarity indexes were computed to evaluate the
      performance of the proposed approach relative to the expert segmentations.
      Empirical results suggested that the proposed segmentation method yielded higher
      similarity measures for both gray matter and white matter as compared with those
      based on the traditional segmentation using the Gaussian mixtures approach.

PMID- 19164076
TI  - Physical-based statistical shape modeling of the levator ani.
AB  - The levator ani is the main muscular support of the pelvic floor organs and
      damage caused by childbirth can affect its function. The full functionality of
      this muscle group is still unknown but it is essential for effective surgical
      planning. To elucidate its functional significance, a physical-based statistical
      shape model was built from the levator ani surfaces of 15 subjects scanned in an
      open access scanner. Simulation of dynamic exercises was performed on the
      resulting surfaces with finite element analysis. Statistical shape modeling was
      performed on the training set consisting of the original and simulated shapes
      along with thickness and strain distributions. Simulation results are presented
      on 15 subjects. The statistical shape model shows good correspondence to inter-
      and intra-subject shape variability, with the modes of variation highlighting
      movement in the posterior of the levator ani as well as in the levator arms.
      Strain distribution plots and the modes of variation show results that correspond
      to clinical findings. Further validation of the technique and a repeatability
      test were performed on four subjects with internal global pressure readings taken
      from a perineometer and five patients suffering from minor pelvic floor disorders
      due to obstructed defaecation. A Mann-Whitney nonparametric test was used to
      compare the normal model fitting to the two subject groups.

PMID- 19164077
TI  - An implementation of CalderOn's method for 3-D limited-view EIT.
AB  - Mathematical interest in electrical impedance tomography has been strong since
      the publication of CalderOn's foundational paper. This paper introduced the idea
      of applying external voltage patterns to a medium such that, assuming that the
      medium is sufficiently close to a constant admittivity, the reconstruction can be
      accomplished directly by inverse Fourier transform. Motivated by CalderOn's
      method, we have developed a variant of the algorithm which is applicable to the
      case of measurement on only a part of the boundary and on discrete electrodes.
      Here we determine voltage or current patterns to apply to the electrodes which
      optimally approximate CalderOn's special functions in the interior. Furthermore,
      in three dimensions and higher, CalderOn's method allows each point in Fourier
      space to be computed in a multiplicity of ways. We show that by making use of the
      inherent redundancy in our measurements, we can significantly improve the quality
      of the static images produced by our algorithm.

PMID- 19164078
TI  - Statistical properties of phase-decorrelation in phase-resolved Doppler optical
      coherence tomography.
AB  - Decorrelation noise limits the ability of phase-resolved Doppler optical
      coherence tomography systems to detect smaller vessels exhibiting slower flow
      velocities, which limits the utility of the technique in many clinical and
      biological settings. An understanding of the statistical properties of
      decorrelation noise can aid in the optimal design of these systems and guide the
      development of noise mitigating strategies. In this work, the statistical
      properties of decorrelation noise are derived from the underlying statistics of
      the coherent imaging system and validated through comparison with empirical
      results and Monte Carlo modeling. Expressions for the noise distribution and the
      noise variance as a function of relevant imaging system parameters are given, and
      the implications of these results on both system and algorithm design are
      discussed.

PMID- 19164079
TI  - Prostate cancer segmentation with simultaneous estimation of Markov random field
      parameters and class.
AB  - Prostate cancer is one of the leading causes of death from cancer among men in
      the United States. Currently, high-resolution magnetic resonance imaging (MRI)
      has been shown to have higher accuracy than trans-rectal ultrasound (TRUS) when
      used to ascertain the presence of prostate cancer. As MRI can provide both
      morphological and functional images for a tissue of interest, some researchers
      are exploring the uses of multispectral MRI to guide prostate biopsies and
      radiation therapy. However, success with prostate cancer localization based on
      current imaging methods has been limited due to overlap in feature space of
      benign and malignant tissues using any one MRI method and the interobserver
      variability. In this paper, we present a new unsupervised segmentation method for
      prostate cancer detection, using fuzzy Markov random fields (fuzzy MRFs) for the
      segmentation of multispectral MR prostate images. Typically, both hard and fuzzy
      MRF models have two groups of parameters to be estimated: the MRF parameters and
      class parameters for each pixel in the image. To date, these two parameters have
      been treated separately, and estimated in an alternating fashion. In this paper,
      we develop a new method to estimate the parameters defining the Markovian
      distribution of the measured data, while performing the data clustering
      simultaneously. We perform computer simulations on synthetic test images and
      multispectral MR prostate datasets to demonstrate the efficacy and efficiency of
      the proposed method and also provide a comparison with some of the commonly used
      methods.

PMID- 19164080
TI  - Vulnerable atherosclerotic plaque elasticity reconstruction based on a
      segmentation-driven optimization procedure using strain measurements: theoretical
      framework.
AB  - It is now recognized that prediction of the vulnerable coronary plaque rupture
      requires not only an accurate quantification of fibrous cap thickness and
      necrotic core morphology but also a precise knowledge of the mechanical
      properties of plaque components. Indeed, such knowledge would allow a precise
      evaluation of the peak cap-stress amplitude, which is known to be a good
      biomechanical predictor of plaque rupture. Several studies have been performed to
      reconstruct a Young's modulus map from strain elastograms. It seems that the main
      issue for improving such methods does not rely on the optimization algorithm
      itself, but rather on preconditioning requiring the best estimation of the plaque
      components' contours. The present theoretical study was therefore designed to
      develop: 1) a preconditioning model to extract the plaque morphology in order to
      initiate the optimization process, and 2) an approach combining a dynamic
      segmentation method with an optimization procedure to highlight the modulogram of
      the atherosclerotic plaque. This methodology, based on the continuum mechanics
      theory prescribing the strain field, was successfully applied to seven
      intravascular ultrasound coronary lesion morphologies. The reconstructed cap
      thickness, necrotic core area, calcium area, and the Young's moduli of the
      calcium, necrotic core, and fibrosis were obtained with mean relative errors of
      12%, 4% and 1%, 43%, 32%, and 2%, respectively.

PMID- 19164081
TI  - Estimation of channelized hotelling observer performance with known class means
      or known difference of class means.
AB  - This paper concerns task-based image quality assessment for the task of
      discriminating between two classes of images. We address the problem of
      estimating two widely-used detection performance measures, SNR and AUC, from a
      finite number of images, assuming that the class discrimination is performed with
      a channelized Hotelling observer. In particular, we investigate the advantage
      that can be gained when either 1) the means of the signal-absent and signal
      present classes are both known, or 2) when the difference of class means is
      known. For these two scenarios, we propose uniformly minimum variance unbiased
      estimators of SNR(2), derive the corresponding sampling distributions and provide
      variance expressions. In addition, we demonstrate how the bias and variance for
      the related AUC estimators may be calculated numerically by using the sampling
      distributions for the SNR(2) estimators. We find that for both SNR(2) and AUC,
      the new estimators have significantly lower bias and mean-square error than the
      traditional estimator, which assumes that the class means, and their difference,
      are unknown.

PMID- 19164082
TI  - Automatic classification for pathological prostate images based on fractal
      analysis.
AB  - Accurate grading for prostatic carcinoma in pathological images is important to
      prognosis and treatment planning. Since human grading is always time-consuming
      and subjective, this paper presents a computer-aided system to automatically
      grade pathological images according to Gleason grading system which is the most
      widespread method for histological grading of prostate tissues. We proposed two
      feature extraction methods based on fractal dimension to analyze variations of
      intensity and texture complexity in regions of interest. Each image can be
      classified into an appropriate grade by using Bayesian, k-NN, and support vector
      machine (SVM) classifiers, respectively. Leave-one-out and k-fold cross
      validation procedures were used to estimate the correct classification rates
      (CCR). Experimental results show that 91.2%, 93.7%, and 93.7% CCR can be achieved
      by Bayesian, k-NN, and SVM classifiers, respectively, for a set of 205
      pathological prostate images. If our fractal-based feature set is optimized by
      the sequential floating forward selection method, the CCR can be promoted up to
      94.6%, 94.2%, and 94.6%, respectively, using each of the above three classifiers.
      Experimental results also show that our feature set is better than the feature
      sets extracted from multiwavelets, Gabor filters, and gray-level co-occurrence
      matrix methods because it has a much smaller size and still keeps the most
      powerful discriminating capability in grading prostate images.

PMID- 19164083
TI  - Identifying anatomical shape difference by regularized discriminative direction.
AB  - Identifying the shape difference between two groups of anatomical objects is
      important for medical image analysis and computer-aided diagnosis. A method
      called "discriminative direction" in the literature has been proposed to solve
      this problem. In that method, the shape difference between groups is identified
      by deforming a shape along the discriminative direction. This paper conducts a
      thorough study about inferring this discriminative direction in an efficient and
      accurate way. First, finding the discriminative direction is reformulated as a
      preimage problem in kernel-based learning. This provides a complementary but
      conceptually simpler solution than the previous method. More importantly, we find
      that a shape deforming along the original discriminative direction cannot
      faithfully maintain its anatomical correctness. This unnecessarily introduces
      spurious shape differences and leads to inaccurate analysis. To overcome this
      problem, this paper further proposes a regularized discriminative direction by
      requiring a shape to conform to its underlying distribution when it deforms. Two
      different approaches are developed to impose the regularization, one from the
      perspective of probability distributions and the other from a geometric point of
      view, and their relationship is discussed. After verifying their superior
      performance through controlled experiments, we apply the proposed methods to
      detecting and localizing the hippocampal shape difference between sexes. We get
      results consistent with other independent research, providing a more compact
      representation of the shape difference compared with the established
      discriminative direction method.

PMID- 19164084
TI  - Morphodynamic analysis of cerebral aneurysm pulsation from time-resolved
      rotational angiography.
AB  - This paper presents a technique to estimate and model patient-specific
      pulsatility of cerebral aneurysms over one cardiac cycle, using 3D rotational X
      ray angiography (3DRA) acquisitions. Aneurysm pulsation is modeled as a time
      varying B-spline tensor field representing the deformation applied to a reference
      volume image, thus producing the instantaneous morphology at each time point in
      the cardiac cycle. The estimated deformation is obtained by matching multiple
      simulated projections of the deforming volume to their corresponding original
      projections. A weighting scheme is introduced to account for the relevance of
      each original projection for the selected time point. The wide coverage of the
      projections, together with the weighting scheme, ensures motion consistency in
      all directions. The technique has been tested on digital and physical phantoms
      that are realistic and clinically relevant in terms of geometry, pulsation and
      imaging conditions. Results from digital phantom experiments demonstrate that the
      proposed technique is able to recover subvoxel pulsation with an error lower than
      10% of the maximum pulsation in most cases. The experiments with the physical
      phantom allowed demonstrating the feasibility of pulsation estimation as well as
      identifying different pulsation regions under clinical conditions.

PMID- 19164086
TI  - The exact mechanism of ethanol-associated carcinogenesis still remains unknown, a
      number of factors may contribute to the development of alcohol-associated cancer,
      including ethanol metabolising enzymes. Editorial.

PMID- 19164085
TI  - Treatment of rabbit elastase-induced aneurysm models by flow diverters:
      development of quantifiable indexes of device performance using digital
      subtraction angiography.
AB  - It has been known for more than a decade that intracranial aneurysms can be
      successfully treated by deploying a porous meshed tube in the parent vessel of
      the aneurysm. Such devices are currently called flow diverters because they
      promote intraneurysmal flow stasis and thrombosis by diverting blood flow away
      from the aneurysm sac. The objective of this study was to use angiographic data
      to quantify and compare the performance of flow diverters of original design in
      successfully occluding an experimental aneurysm model. Three different
      configurations of a novel flow diverter with varying porosities and pore
      densities were implanted in 30 rabbit elastase-induced aneurysms. Temporal
      variations in angiographic contrast intensity within the aneurysms were fit to a
      mathematical model. Optimized model parameters were supplemented by the
      angiographic percentage aneurysm occlusion and an angiographic measure of device
      flexibility to derive composite scores of performance. Angiographic
      quantification further suggested a parameter, which could be employed to estimate
      long-term aneurysm occlusion probabilities immediately after treatment.
      Performance scores showed that the device with a porosity of 70% and pore density
      of 18 pores/mm (2) performed better than devices with 65% porosity, 14 pores/mm
      (2), and 70% porosity, 12 pores/mm (2) with relative efficacies of 100%, 84%, and
      76%, respectively. The pore density of flow diverters, rather than porosity, may
      thus be a critical factor modulating device efficacy. A value of the prognostic
      parameter of less than 30 predicted greater than 97% angiographic aneurysm
      occlusion over six months with a sensitivity of 73% and specificity of 82%.

PMID- 19164087
TI  - Alleles of alcohol and acetaldehyde metabolism genes modulate susceptibility to
      oesophageal cancer from alcohol consumption.

PMID- 19164088
TI  - Comparative genomics of aldehyde dehydrogenase 5a1 (succinate semialdehyde
      dehydrogenase) and accumulation of gamma-hydroxybutyrate associated with its
      deficiency.
AB  - Succinic semialdehyde dehydrogenase (SSADH; aldehyde dehydrogenase 5A1 [ALDH5A1];
      locus 6p22) occupies a central position in central nervous system (CNS)
      neurotransmitter metabolism as one of two enzymes necessary for gamma
      aminobutyric acid (GABA) recycling from the synaptic cleft. Its importance is
      highlighted by the neurometabolic disease associated with its inherited
      deficiency in humans, as well as the severe epileptic phenotype observed in
      Aldh5a1(-/-) knockout mice. Expanding evidence now suggests, however, that even
      subtle decreases in human SSADH activity, associated with rare and common single
      nucleotide polymorphisms, may produce subclinical pathological effects. SSADH, in
      conjunction with aldo-keto reductase 7A2 (AKR7A2), represent two neural enzymes
      responsible for further catabolism of succinic semialdehyde, producing either
      succinate (SSADH) or gamma-hydroxybutyrate (GHB; AKR7A2). A GABA analogue, GHB is
      a short-chain fatty alcohol with unusual properties in the CNS and a long
      pharmacological history. Moreover, SSADH occupies a further role in the CNS as
      the enzyme responsible for further metabolism of the lipid peroxidation aldehyde
      4-hydroxy-2-nonenal (4-HNE), an intermediate known to induce oxidant stress.
      Accordingly, subtle decreases in SSADH activity may have the capacity to lead to
      regional accumulation of neurotoxic intermediates (GHB, 4-HNE). Polymorphisms in
      SSADH gene structure may also associate with quantitative traits, including
      intelligence quotient and life expectancy. Further population-based studies of
      human SSADH activity promise to reveal additional properties of its function and
      additional roles in CNS tissue.

PMID- 19164089
TI  - Effect of the allelic variants of aldehyde dehydrogenase ALDH2*2 and alcohol
      dehydrogenase ADH1B*2 on blood acetaldehyde concentrations.
AB  - Alcoholism is a complex behavioural disorder. Molecular genetics studies have
      identified numerous candidate genes associated with alcoholism. It is crucial to
      verify the disease susceptibility genes by correlating the pinpointed allelic
      variations to the causal phenotypes. Alcohol dehydrogenase (ADH) and aldehyde
      dehydrogenase (ALDH) are the principal enzymes responsible for ethanol metabolism
      in humans. Both ADH and ALDH exhibit functional polymorphisms among racial
      populations; these polymorphisms have been shown to be the important genetic
      determinants in ethanol metabolism and alcoholism. Here, we briefly review recent
      advances in genomic studies of human ADH/ALDH families and alcoholism, with an
      emphasis on the pharmacogenetic consequences of venous blood acetaldehyde in the
      different ALDH2 genotypes following the intake of various doses of ethanol. This
      paper illustrates a paradigmatic example of phenotypic verifications in a
      protective disease gene for substance abuse.

PMID- 19164090
TI  - Whole-genome approach implicates CD44 in cellular resistance to carboplatin.
AB  - Carboplatin is a chemotherapeutic agent used in the management of many cancers,
      yet treatment is limited by resistance and toxicities. To achieve a better
      understanding of the genetic contribution to carboplatin resistance or
      toxicities, lymphoblastoid cell lines from 34 large Centre d'Etude du
      Polymorphisme Humain pedigrees were utilised to evaluate interindividual
      variation in carboplatin cytotoxicity. Significant heritability, ranging from
      0.17-0.36 (p = 1 x 10(-7) to 9 x 10(-4)), was found for cell growth inhibition
      following 72-hour treatment at each carboplatin concentration (10, 20, 40 and 80
      microM) and IC(50) (concentration for 50 per cent cell growth inhibition).
      Linkage analysis revealed 11 regions with logarithm of odds (LOD) scores greater
      than 1.5. The highest LOD score on chromosome 11 (LOD = 3.36, p = 4.2 x 10(-5))
      encompasses 65 genes within the 1 LOD confidence interval for the carboplatin IC
      50 . We further analysed the IC(50) phenotype with a linkage-directed association
      analysis using 71 unrelated HapMap and Perlegen cell lines and identified 18
      single nucleotide polymorphisms within eight genes that were significantly
      associated with the carboplatin IC(50) (p < 3.6 x 10(-5); false discovery rate <5
      per cent). Next, we performed linear regression on the baseline expression and
      carboplatin IC(50) values of the eight associated genes, which identified the
      most significant correlation between CD44 expression and IC(50) (r(2)= 0.20; p =
      6 x 10(-4)). The quantitative real-time polymerase chain reaction further
      confirmed a statistically significant difference in CD44 expression levels
      between carboplatin-resistant and -sensitive cell lines (p = 5.9 x 10(-3)).
      Knockdown of CD44 expression through small interfering RNA resulted in increased
      cellular sensitivity to carboplatin (p < 0.01). Our whole-genome approach using
      molecular experiments identified CD44 as being important in conferring cellular
      resistance to carboplatin.

PMID- 19164091
TI  - Orientation, distance, regulation and function of neighbouring genes.
AB  - The sequencing of the human genome has allowed us to observe globally and in
      detail the arrangement of genes along the chromosomes. There are multiple lines
      of evidence that this arrangement is not random, both in terms of intergenic
      distances and orientation of neighbouring genes. We have undertaken a systematic
      evaluation of the spatial distribution and orientation of known genes across the
      human genome. We used genome-level information, including phylogenetic
      conservation, single nucleotide polymorphism density and correlation of gene
      expression to assess the importance of this distribution. In addition to
      confirming and extending known properties of the genome, such as the significance
      of gene deserts and the importance of 'head to head' orientation of gene pairs in
      proximity, we provide significant new observations that include a smaller average
      size for intervals separating the 3' ends of neighbouring genes, a correlation of
      gene expression across tissues for genes as far as 100 kilobases apart and
      signatures of increasing positive selection with decreasing interval size
      surprisingly relaxing for intervals smaller than approximately 500 base pairs.
      Further, we provide extensive graphical representations of the genome-wide data
      to allow for observations and comparisons beyond what we address.

PMID- 19164092
TI  - LIPE C-60G influences the effects of physical activity on body fat and plasma
      lipid concentrations: the Quebec Family Study.
AB  - A large body of evidence suggests that the environment plays an important role in
      the development of obesity. The hormone-sensitive lipase (encoded by the LIPE
      gene) is an intracellular enzyme that mobilises fat stores in a hormone
      stimulated manner. The aim of the present study was to determine the effects of
      the LIPE C-60G polymorphism on body fat and plasma lipid and lipoprotein
      concentrations, and to test for its interaction with physical activity. The LIPE
      C-60G polymorphism was genotyped in 862 subjects from the Quebec Family Study.
      Body mass index (BMI), fat mass, percentage body fat, abdominal fat areas
      assessed by computed tomography, and detailed fasting plasma lipid and
      lipoprotein profiles were measured. Levels of physical activity were estimated
      using a three-day diary, and a moderate to strenuous physical activity score was
      retained for this study. The main effects of the LIPE C-60G polymorphism,
      physical activity and their interaction were determined by regression analyses
      separately in men and women using the MIXED model procedure. In men, we observed
      significant gene-physical activity interactions for BMI (p = 0.006), fat mass (p
      = 0.04), abdominal visceral fat area (p = 0.005) and plasma cholesterol (C) high
      density lipoprotein cholesterol (HDL-C) ratio (p = 0.003). A high level of
      physical activity was associated with reduced adiposity and a lower plasma-C/HDL
      C ratio, but only in non-carriers of the genetic variant (G-60 allele). In women,
      no evidence of a gene by physical activity interaction was observed, except for
      subcutaneous abdominal fat (p = 0.05). These results suggest that the
      associations between physical activity and body fat and plasma lipoprotein/lipid
      concentrations in men are dependent on the LIPE C-60G polymorphism, and highlight
      the importance of taking into account the role of gene-physical activity
      interactions in candidate gene studies of obesity and obesity-related traits.

PMID- 19164093
TI  - Novel variants of major drug-metabolising enzyme genes in diverse African
      populations and their predicted functional effects.
AB  - Pharmacogenetics enables personalised therapy based on genetic profiling and is
      increasingly applied in drug discovery. Medicines are developed and used together
      with pharmacodiagnostic tools to achieve desired drug efficacy and safety
      margins. Genetic polymorphism of drug-metabolising enzymes such as cytochrome
      P450s (CYPs) and N-acetyltransferases (NATs) has been widely studied in Caucasian
      and Asian populations, yet studies on African variants have been less extensive.
      The aim of the present study was to search for novel variants of CYP2C9 , CYP2C19
      , CYP2D6 and NAT2 genes in Africans, with a particular focus on their prevalence
      in different populations, their relevance to enzyme functionality and their
      potential for personalised therapy. Blood samples from various ethnic groups were
      obtained from the AiBST Biobank of African Populations. The nine exons and exon
      intron junctions of the CYP genes and exon 2 of NAT2 were analysed by direct DNA
      sequencing. Computational tools were used for the identification, haplotype
      analysis and prediction of functional effects of novel single nucleotide
      polymorphisms (SNPs). Novel SNPs were discovered in all four genes, grouped to
      existing haplotypes or assigned new allele names, if possible. The functional
      effects of non-synonymous SNPs were predicted and known African-specific variants
      were confirmed, but no significant differences were found in the frequencies of
      SNPs between African ethnicities. The low prevalence of our novel variants and
      most known functional alleles is consistent with the generally high level of
      diversity in gene loci of African populations. This indicates that profiles of
      rare variants reflecting interindividual variability might become the most
      relevant pharmacodiagnostic tools explaining Africans' diversity in drug
      response.

PMID- 19164094
TI  - Association tests and software for copy number variant data.
AB  - Recent studies have suggested that copy number variation (CNV) significantly
      contributes to genetic predisposition to several common disorders. These
      findings, combined with the imperfect tagging of CNVs by single nucleotide
      polymorphisms (SNPs), have motivated the development of association studies
      directly targeting CNVs. Several assays, including comparative genomic
      hybridisation arrays, SNP genotyping arrays, or DNA quantification through real
      time polymerase chain reaction analysis, allow direct assessment of CNV status in
      cohorts sufficiently large to provide adequate statistical power for association
      studies. When analysing data provided by these assays, association tests for CNV
      data are not fundamentally different from SNP-based association tests. The main
      difference arises when the quality of the CNV assay is not sufficient to convert
      unequivocally the raw measurement into discrete calls - a common issue, given the
      technological limitations of current CNV assays. When this is the case,
      association tests are more appropriately based on the raw continuous measurement
      provided by the CNV assay, instead of potentially inaccurate discrete calls, thus
      motivating the development of new statistical methods. Here, the programs
      available for CNV association testing for case control or family data are
      reviewed, using either discrete calls or raw continuous data.

PMID- 19164098
TI  - Applying rapid serial visual presentation to adolescent sexual offenders:
      attentional bias as a measure of deviant sexual interest?
AB  - Attentional bias toward child images is assessed among adolescent sexual
      offenders and nonsexual offenders using the rapid serial visual presentation
      (RSVP) method, which measures the effects of "attentional blink." Twenty
      adolescent sexual offenders against children and 26 nonsexual offenders are asked
      to identify a child or animal image and then a second image in streams of 10
      images. A stronger attentional blink effect is expected for offenders against
      children after viewing child rather than animal images. However, the expected
      differences between offender groups are not found. It is questioned whether the
      RSVP images can elicit a response in adolescent sexual offenders indicative of
      DSI. The clinical utility of applying the RSVP assessment with adolescents rather
      than adults is also queried because (a) adolescents' cognitive abilities may not
      allow them to conceptualize and concentrate on the assessment in its present form
      and (b) deviant sexual interest may be evident to different degrees in adolescent
      sexual offenders.

PMID- 19164095
TI  - Analysis and update of the human solute carrier (SLC) gene superfamily.
AB  - The solute-carrier gene (SLC) superfamily encodes membrane-bound transporters.
      The SLC superfamily comprises 55 gene families having at least 362 putatively
      functional protein-coding genes. The gene products include passive transporters,
      symporters and antiporters, located in all cellular and organelle membranes,
      except, perhaps, the nuclear membrane. Transport substrates include amino acids
      and oligopeptides, glucose and other sugars, inorganic cations and anions (H(+),
      HCO(3)(-), Cl(-), Na(+), K(+), Ca(2+), Mg(2+), PO(4)(3-), HPO(4)(2-), H(2)PO(4)(
      ), SO(4)(2-), C(2)O(4)(2-), OH(-), CO(3)(2-)), bile salts, carboxylate and other
      organic anions, acetyl coenzyme A, essential metals, biogenic amines,
      neurotransmitters, vitamins, fatty acids and lipids, nucleosides, ammonium,
      choline, thyroid hormone and urea. Contrary to gene nomenclature commonly
      assigned on the basis of evolutionary divergence (http://www.genenames.org/), the
      SLC gene superfamily has been named based largely on transporter function by
      proteins having multiple transmembrane domains. Whereas all the transporters
      exist for endogenous substrates, it is likely that drugs, non-essential metals
      and many other environmental toxicants are able to 'hitch-hike' on one or another
      of these transporters, thereby enabling these moieties to enter (or leave) the
      cell. Understanding and characterising the functions of these transporters is
      relevant to medicine, genetics, developmental biology, pharmacology and cancer
      chemotherapy.

PMID- 19164099
TI  - Activation of lumbar spinal wide-dynamic range neurons by a sanshool derivative.
AB  - The enigmatic sensation of tingle involves the activation of primary sensory
      neurons by hydroxy-alpha-sanshool, a tingly agent in Szechuan peppers, by
      inhibiting two-pore potassium channels. Central mechanisms mediating tingle
      sensation are unknown. We investigated whether a stable derivative of sanshool
      isobutylalkenyl amide (IBA)-excites wide-dynamic range (WDR) spinal neurons that
      participate in transmission of chemesthetic information from the skin. In
      anesthetized rats, the majority of WDR and low-threshold units responded to
      intradermal injection of IBA in a dose-related manner over a >5-min time course
      and exhibited tachyphylaxis at higher concentrations (1 and 10%). Almost all WDR
      and low-threshold units additionally responded to the pungent agents mustard oil
      (allyl isothiocyanate) and/or capsaicin, prompting reclassification of the low
      threshold cells as WDR. The results are discussed in terms of the functional role
      of WDR neurons in mediating tingle sensation.

PMID- 19164100
TI  - Sudden drop in ground support produces force-related unload response in human
      overground walking.
AB  - Humans maneuver easily over uneven terrain. To maintain smooth and efficient gait
      the motor system needs to adapt the locomotor output to the walking environment.
      In the present study we investigate the role of sensory feedback in adjusting the
      soleus muscle activity during overground walking in 19 healthy volunteers.
      Subjects walked unrestrained over a hydraulically actuated platform. On random
      trials the platform was accelerated downward at 0.8 g, unloading the plantar
      flexor muscles in midstance or late stance. The drop of the platform resulted in
      a significant depression of the soleus muscle activity of -17.9% (SD 2) and 
      21.4% (SD 2), with an onset latency of 49 ms (SD 1) and 45 ms (SD 1) in midstance
      and late stance, respectively. Input to the vestibular apparatus (i.e., the head
      acceleration) occurred at a latency 10.0 ms (SD 2.4) following the drop and ankle
      dorsiflexion velocity was decreased starting 22 ms (SD 15) after the drop. To
      investigate the role of length- and velocity-sensitive afferents on the
      depression in soleus muscle activity, the ankle rotation was arrested by using an
      ankle foot orthotic as the platform was dropped. Preventing the ankle movement
      did not significantly change the soleus depression in late stance [-18.2% (SD
      15)], whereas the depression in midstance was removed [+4.9% (SD 13)]. It is
      concluded that force feedback from ankle extensors increases the locomotor output
      through positive feedback in late stance. In midstance the effect of force
      feedback was not observed, suggesting that spindle afferents may have a more
      significant effect on the output during this phase of the step cycle.

PMID- 19164101
TI  - Triggering slow waves during NREM sleep in the rat by intracortical electrical
      stimulation: effects of sleep/wake history and background activity.
AB  - In humans, non-rapid eye movement (NREM) sleep slow waves occur not only
      spontaneously but can also be induced by transcranial magnetic stimulation. Here
      we investigated whether slow waves can also be induced by intracortical
      electrical stimulation during sleep in rats. Intracortical local field potential
      (LFP) recordings were obtained from several cortical locations while the frontal
      or the parietal area was stimulated intracortically with brief (0.1 ms)
      electrical pulses. Recordings were performed in early sleep (1st 2-3 h after
      light onset) and late sleep (6-8 h after light onset). The stimuli reliably
      triggered LFP potentials that were visually indistinguishable from naturally
      occurring slow waves. The induced slow waves shared the following features with
      spontaneous slow waves: they were followed by spindling activity in the same
      frequency range ( approximately 15 Hz) as spontaneously occurring sleep spindles;
      they propagated through the neocortex from the area of the stimulation; and
      compared with late sleep, waves triggered during early sleep were larger, had
      steeper slopes and fewer multipeaks. Peristimulus background spontaneous activity
      had a profound influence on the amplitude of the induced slow waves: they were
      virtually absent if the stimulus was delivered immediately after the spontaneous
      slow wave. These results show that in the rat a volley of electrical activity
      that is sufficiently strong to excite and recruit a large cortical neuronal
      population is capable of inducing slow waves during natural sleep.

PMID- 19164102
TI  - Distinct subtypes of cholecystokinin (CCK)-containing interneurons of the
      basolateral amygdala identified using a CCK promoter-specific lentivirus.
AB  - The basolateral amygdala (BLA) is critical for the formation of emotional
      memories. Little is known about the physiological properties of BLA interneurons,
      which can be divided into four subtypes based on their immunocytochemical
      profiles. Cholecystokinin (CCK) interneurons play critical roles in feedforward
      inhibition and behavioral fear responses. Evidence suggests that interneurons
      within a subgroup can display heterogeneous physiological properties. However,
      little is known about the physiological properties of CCK interneurons in the BLA
      and/or whether they represent a homogeneous or heterogeneous population. To
      address this question, we generated a lentivirus-expressing GFP under the control
      of the CCK promoter to identify CCK neurons in vivo. We combined this with whole
      cell patch-clamp recording techniques to examine the physiological properties of
      CCK-containing interneurons of the rat BLA. Here, we describe the physiological
      properties of 57 cells recorded in current-clamp mode; we used hierarchical
      cluster and discriminant function analysis to demonstrate that CCK interneurons
      can be segregated into three distinct subtypes (I, II, III) based on their
      passive and active membrane properties. Additionally, Type II neurons could be
      further separated into adapting and nonadapting types based on their rates of
      spike frequency adaptation. These data suggest that CCK interneurons of the BLA
      are a heterogeneous population and may be functionally distinct subpopulations
      that differentially contribute to the processing of emotionally salient stimuli.

PMID- 19164103
TI  - Mapping and identification of GABAergic neurons in transgenic mice projecting to
      cardiac vagal neurons in the nucleus ambiguus using photo-uncaging.
AB  - The neural control of heart rate is determined primarily by the activity of
      preganglionic parasympathetic cardiac vagal neurons (CVNs) originating in the
      nucleus ambiguus (NA) in the brain stem. GABAergic inputs to CVNs play an
      essential role in determining the activity of these neurons including a robust
      inhibition during each inspiratory burst. The origin of GABAergic innervation has
      yet to be determined however. A transgenic mouse line expressing green florescent
      protein (GFP) in GABAergic cells was used in conjunction with caged glutamate to
      identify both clusters and individual GABAergic neurons that evoke inhibitory
      GABAergic synaptic responses in CVNs. Transverse slices were taken with CVNs
      patch-clamped in the whole cell configuration. Sections containing both the pre
      Botzinger complex as well as the calamus scriptorius were divided into
      approximately 90 quadrants, each 200 x 200 microm and were sequentially
      photostimulated. Inhibitory post synaptic currents (IPSCs) were recorded in CVNs
      after a 5-ms photostimulation of 50 microM caged glutamate. The four areas that
      contained GABAergic cells projecting to CVNs were 200 microm medial, 400 microm
      medial, 200 microm ventral, and 1,200 microm dorsal and 1,000 microm medial to
      patched CVNs. Once foci of GABAergic cells projecting to CVNs were determined,
      photostimulation of individual GABAergic neurons was conducted. The results from
      this study suggest that GABAergic cells located in four specific areas project to
      CVNs, and that these cells can be individually identified and stimulated using
      photouncaging to recruit GABAergic neurotransmission to CVNs.

PMID- 19164105
TI  - Saccade adaptation specific to visual context.
AB  - When saccades consistently overshoot their targets, saccade amplitudes gradually
      decrease, thereby maintaining accuracy. This adaptive process has been seen as a
      form of motor learning that copes with changes in physical parameters of the eye
      and its muscles, brought about by aging or pathology. One would not expect such a
      motor-repair mechanism to be specific to the visual properties of the target
      stimulus. We had subjects make saccades to sudden movements of either of two
      targets-a steadily illuminated circle or a flickering circle-one of which stepped
      back during each saccade it elicited, simulating the effect of a hypermetric
      saccade. Saccade gain (saccade amplitude/target amplitude) decreased by 15% for
      the target that stepped back versus 6% for the target that did not step back.
      Most of the change in gain between successive blocks of trials of each type
      occurred on the first saccade of the block, decreasing by 0.12 on the first trial
      of a step-back block and increasing by 0.1 on the first trial of a no-step-back
      block. The differential adaptation of the two targets required postsaccadic
      feedback of both target types, as shown in a separate experiment, in which
      saccades to only one target received feedback, and the gain did not differ
      between the two target types. This demonstration that a context defined by a
      visual stimulus can serve as an effective cue for switching saccade gain between
      states suggests that saccade adaptation may have a heretofore unsuspected
      dimension of adaptability.

PMID- 19164106
TI  - Odor-induced persistent discharge of mitral cells in the mouse olfactory bulb.
AB  - Short-term retention of sensory information in the form of persistent activity of
      central neurons plays a key role in transforming a brief sensory stimulation into
      longer-lasting brain responses. The olfactory system uses this transformation for
      various functional purposes, but the underlying neuronal mechanisms remain
      elusive. Here, we recorded odor-evoked, single-unit spike responses of mitral and
      tufted (M/T) cells in the mouse olfactory bulb (OB) under urethane anesthesia and
      examined the neuronal mechanisms of the persistent discharge (PD) of M/T cells
      that outlasts the odor stimulus for tens of seconds. The properties of the
      persistent afterdischarge that occurred after odor stimulation were distinct from
      those of odor-induced immediate spike responses in terms of the magnitude,
      odorant specificity, and odorant concentration-response relationship. This
      suggests that neuronal mechanisms other than prolonged input from olfactory
      sensory neurons are involved in generating these afterdischarges. Metabotropic
      glutamate receptor 1 (mGluR1) is expressed in the dendrites of M/T cells and is
      thought to participate in intraglomerular interactions among M/T cells. In OBs
      lacking mGluR1, or treated locally with an mGluR1-selective antagonist, the
      duration of the odor-induced spike responses was significantly lower than that in
      control OBs, indicating that mGluR1 within the bulbar neuronal circuits
      participates in the PD generation. These results suggest that neuronal circuits
      in the OB can actively prolong the odor-induced spike activity of bulbar output
      neurons and thus transform a brief odor input into longer-lasting activity in the
      central olfactory system.

PMID- 19164104
TI  - Deep brain stimulation of the globus pallidus internus in the parkinsonian
      primate: local entrainment and suppression of low-frequency oscillations.
AB  - Competing theories seek to account for the therapeutic effects of high-frequency
      deep brain stimulation (DBS) of the internal globus pallidus (GPi) for medically
      intractable Parkinson's disease. To investigate this question, we studied the
      spontaneous activity of 102 pallidal neurons during GPiDBS in two macaques
      rendered parkinsonian by administration of MPTP. Stimulation through
      macroelectrodes in the GPi (> or =200 microA at 150 Hz for 30 s) reduced rigidity
      in one animal and increased spontaneous movement in both. Novel artifact
      subtraction methods allowed uninterrupted single-unit recording during
      stimulation. GPiDBS induced phasic (78% of cells) or sustained (22%) peristimulus
      changes in firing in both pallidal segments. A subset of cells responded at short
      latency (<2 ms) in a manner consistent with antidromic driving. Later phasic
      increases clustered at 3- to 5-ms latency. Stimulation-induced decreases were
      either phasic, clustered at 1-3 ms, or sustained, showing no peristimulus
      modulation. Response latency and magnitude often evolved over 30 s of
      stimulation, but responses were relatively stable by the end of that time. GPiDBS
      reduced mean firing rates modestly and only in GPi (-6.9 spikes/s). Surprisingly,
      GPiDBS had no net effect on the prevalence or structure of burst firing. GPiDBS
      did reduce the prevalence of synchronized low-frequency oscillations. Some cell
      pairs became synchronized instead at the frequency of stimulation. Suppression of
      low-frequency oscillations did not require high-frequency synchronization,
      however, or even the presence of a significant peristimulus response. In summary,
      the therapeutic effects of GPiDBS may be mediated by an abolition of low
      frequency synchronized oscillations as a result of phasic driving.

PMID- 19164107
TI  - The neural correlates of intending not to do something.
AB  - There has been plenty of research concerning the representation of voluntary
      action in the human brain. However, the question of how we represent the
      voluntary omission of an action has been largely neglected. Therefore this study
      aimed at investigating the representation of intentionally not doing something by
      means of event-related potentials (ERPs). Free-choice nonactions elicit similar
      evoked potentials as free-choice actions and instructed actions (augmented P2 and
      attenuated N2), which leads us to assume that the voluntary intention, not the
      overt nonaction, is the characteristic feature of free-choice nonaction. Beyond
      that we reveal differences between free-choice nonactions and instructed
      nonactions that resemble the typical N2 and P3 augmentation usually seen for NoGo
      trials in Go/NoGo paradigms, with the difference that the free-choice nonaction
      ERP takes the place of the typical Go ERP.

PMID- 19164108
TI  - Position sensitivity of feline paraspinal muscle spindles to vertebral movement
      in the lumbar spine.
AB  - Muscle spindles contribute to sensorimotor control by supplying feedback
      regarding muscle length and consequently information about joint position. While
      substantial study has been devoted to determining the position sensitivity of
      spindles in limb muscles, there appears to be no data on their sensitivity in the
      low back. We determined the relationship between lumbar paraspinal muscle spindle
      discharge and paraspinal muscle lengthening estimated from controlled cranialward
      movement of the L(6) vertebra in anesthetized cats. Ramp (0.4 mm/s) and hold
      displacements (0.2, 0.4, 0.6, 0.8, and 1.2 mm for 2.5 s) were applied at the L(6)
      spinous process. Position sensitivity was defined as the slope of the
      relationship between the estimated increase in muscle length and mean
      instantaneous frequency at each length. To enable comparisons with appendicular
      muscle spindles where joint angle was measured, we also calculated sensitivity in
      terms of the L(6) and L(7) intervertebral flexion angle (IVA). This angle was
      estimated from measurements of facet joint capsule strain (FJC) based on a
      previously established relationship between IVA and FJC strain in the cat lumbar
      vertebral column during lumbar flexion. Single-unit recordings were obtained from
      12 muscle spindle afferents. Longissimus and multifidus muscles contained the
      receptive field of 10 and 2 afferents, respectively. Mean position sensitivity
      was 16.3 imp.s(-1).mm(-1) [10.6-22.1, 95% confidence interval (CI), P < 0.001].
      Mean angular sensitivity was 5.2 imp.s(-1). degrees (-1) (2.6-8.0, P < 0.003).
      These slope estimates were more than 3.5 times greater compared with appendicular
      muscle spindles, and their CIs did not contain previous slope estimates for the
      sensitivity of appendicular spindles from the literature. Potential reasons for
      and the significance of the apparently high position sensitivity in the lumbar
      spine are discussed.

PMID- 19164109
TI  - Short-term temporal discounting of reward value in human ventral striatum.
AB  - Delayed rewards lose their value for economic decisions and constitute weaker
      reinforcers for learning. Temporal discounting of reward value already occurs
      within a few seconds in animals, which allows investigations of the underlying
      neurophysiological mechanisms. However, it is difficult to relate these
      mechanisms to human discounting behavior, which is usually studied over days and
      months and may engage different brain processes. Our study aimed to bridge the
      gap by using very short delays and measuring human functional magnetic resonance
      responses in one of the key reward centers of the brain, the ventral striatum. We
      used psychometric methods to assess subjective timing and valuation of monetary
      rewards with delays of 4.0-13.5 s. We demonstrated hyperbolic and exponential
      decreases of striatal responses to reward predicting stimuli within this time
      range, irrespective of changes in reward rate. Lower reward magnitudes induced
      steeper behavioral and striatal discounting. By contrast, striatal responses
      following the delivery of reward reflected the uncertainty in subjective timing
      associated with delayed rewards rather than value discounting. These data suggest
      that delays of a few seconds affect the neural processing of predicted reward
      value in the ventral striatum and engage the temporal sensitivity of reward
      responses. Comparisons with electrophysiological animal data suggest that ventral
      striatal reward discounting may involve dopaminergic and orbitofrontal inputs.

PMID- 19164110
TI  - Covert representation of second-next movement in the pre-supplementary motor area
      of monkeys.
AB  - We attempted to analyze the nature of premovement activity of neurons in medial
      motor areas [supplementary motor area (SMA) and pre-SMA] from a perspective of
      coding multiple movements. Monkeys were trained to perform a series of two
      movements with an intervening delay: supination or pronation with either forearm.
      Movements were initially instructed with visual signals but had to be remembered
      thereafter. Although a well-known type of premovement activity representing the
      forthcoming movements was found in the two areas, we found an unexpected type of
      activity that represented a second-next movement before initiating the first of
      the two movements. Typically in the pre-SMA, such activity selective for the
      second-next movement peaked before the initiation of the first movement, decayed
      thereafter, and remained low in magnitude while initiating the second movement.
      This type of activity may tentatively hold information for the second movement
      while initiating the first. That information may be fed into another group of
      neurons that themselves build a preparatory activity required to plan the second
      movements. Alternatively, the activity could serve as a signal to inhibit a
      premature exertion of the motor command for the second movement.

PMID- 19164111
TI  - Representation of dynamic interaural phase difference in auditory cortex of awake
      rhesus macaques.
AB  - Neurons in auditory cortex of awake primates are selective for the spatial
      location of a sound source, yet the neural representation of the binaural cues
      that underlie this tuning remains undefined. We examined this representation in
      283 single neurons across the low-frequency auditory core in alert macaques,
      trained to discriminate binaural cues for sound azimuth. In response to binaural
      beat stimuli, which mimic acoustic motion by modulating the relative phase of a
      tone at the two ears, these neurons robustly modulate their discharge rate in
      response to this directional cue. In accordance with prior studies, the preferred
      interaural phase difference (IPD) of these neurons typically corresponds to
      azimuthal locations contralateral to the recorded hemisphere. Whereas binaural
      beats evoke only transient discharges in anesthetized cortex, neurons in awake
      cortex respond throughout the IPD cycle. In this regard, responses are consistent
      with observations at earlier stations of the auditory pathway. Discharge rate is
      a band-pass function of the frequency of IPD modulation in most neurons (73%),
      but both discharge rate and temporal synchrony are independent of the direction
      of phase modulation. When subjected to a receiver operator characteristic
      analysis, the responses of individual neurons are insufficient to account for the
      perceptual acuity of these macaques in an IPD discrimination task, suggesting the
      need for neural pooling at the cortical level.

PMID- 19164113
TI  - Effects of neoadjuvant combined chemotherapy and radiation therapy on the CT
      evaluation of resectability and staging in patients with pancreatic head cancer.
AB  - PURPOSE: To evaluate the effect of neoadjuvant combined chemotherapy and
      radiation therapy (CCRT) on preoperative accuracy of multidetector computed
      tomography (CT) for resectability and tumor staging in patients with pancreatic
      head cancer. MATERIALS AND METHODS: This retrospective study received
      institutional review board approval and was exempted from informed consent
      requirements. From May 2002 to March 2007, 38 patients with pancreatic head
      adenocarcinoma underwent multidetector CT before surgery. Of these, 12 patients
      received neoadjuvant CCRT. Imaging findings were evaluated for tumor
      resectability and tumor staging. Surgical and pathologic results were used as the
      reference standard. The accuracy of resectability and individual components of
      each T category were compared between the patients with neoadjuvant CCRT and
      without it by using the chi(2) test or Fisher exact test. A P of less than .05
      was considered as significant. RESULTS: The accuracy in determining resectability
      was 83% (10 of 12) in patients who had received neoadjuvant CCRT and 81% (21 of
      26) in patients who had not, without significant difference (P > .05). Of 32
      patients who underwent pancreaticoduodenectomy, histopathologic tumor staging was
      reported for T1 (n = 2), T2 (n = 1), and T3 (n = 9) lesions in patents with
      neoadjuvant CCRT (n = 12), and for T3 in all patients without neoadjuvant CCRT (n
      = 20). T-staging accuracy was 67% (eight of 12) with neoadjuvant CCRT and 95% (19
      of 20) without it, with a significant difference (P = .0185). CONCLUSION:
      Neoadjuvant CCRT reduces the accuracy of tumor restaging after treatment of
      pancreatic head cancer, but this effect is not so great as to affect the
      determination of resectability.

PMID- 19164112
TI  - Impairment of postural control in rabbits with extensive spinal lesions.
AB  - Our previous studies on rabbits demonstrated that the ventral spinal pathways are
      of primary importance for postural control in the hindquarters. After ventral
      hemisection, postural control did not recover, whereas after dorsal or lateral
      hemisection it did. The aim of this study was to examine postural capacity of
      rabbits after more extensive lesion (3/4 section of the spinal cord at T(12)
      level), that is, with only one ventral quadrant spared (VQ animals). They were
      tested before (control) and after lesion on the platform periodically tilted in
      the frontal plane. In control animals, tilts of the platform regularly elicited
      coordinated electromyographic (EMG) responses in the hindlimbs, which resulted in
      generation of postural corrections and in maintenance of balance. In VQ rabbits,
      the EMG responses appeared only in a part of tilt cycles, and they could be
      either correctly or incorrectly phased in relation to tilts. Because of a reduced
      value and incorrect phasing of EMG responses on both sides, this muscle activity
      did not cause postural corrective movements in the majority of rabbits, and the
      body swayed together with the platform. In these rabbits, the ability to perform
      postural corrections did not recover during the whole period of observation (< or
      =30 days). Low probability of correct EMG responses to tilts in most rabbits as
      well as an appearance of incorrect responses to tilts suggest that the spinal
      reflex chains, necessary for postural control, have not been specifically
      selected by a reduced supraspinal drive transmitted via a single ventral
      quadrant.

PMID- 19164114
TI  - Comparative study of transcatheter renal arterial embolization with and without
      closed renal circuit: pharmacokinetic and histologic assessment in pigs.
AB  - PURPOSE: To assess the degree of renal necrosis and the leakage of absolute
      ethanol by using two methods: transcatheter renal artery embolization (TAE) and
      TAE performed with a closed renal circuit (CRC) (TAE/CRC), both performed by
      using ethanol and iodized oil, in a pig model. MATERIALS AND METHODS: All animal
      experiments were conducted in accordance with our university guidelines for
      animal care and experimentation. Fourteen pigs were classified in two groups:
      standard TAE and TAE/CRC groups. In the TAE/CRC group, the renal artery and vein
      were occluded with balloon catheters; in the TAE group, only the renal artery was
      occluded. An emulsion of absolute ethanol (0.5 mL per kilogram of body weight)
      and iodized oil (emulsion ratio, 4:1) was injected in the renal artery in both
      groups. In the TAE/CRC group, we aspirated the blood containing the emulsion via
      the renal vein during arterial infusion. We measured the ethanol concentrations
      of the systemic circulation. Four days after embolization, the kidneys in both
      groups were removed and histopathologic examination was performed and results
      were compared. RESULTS: The mean systemic ethanol concentration was less than 0.1
      mg/mL in the TAE/CRC group and 0.28 mg/mL +/- 0.15 (standard deviation) in the
      TAE group (P < .002). In both groups, about 90% of the kidney was shown
      histopathologically to have undergone coagulation necrosis (no significant
      difference). The frequency of venous thrombus formation was significantly lower
      (P = .009) in the TAE/CRC group. CONCLUSION: TAE/CRC dramatically reduces ethanol
      leakage to the systemic circulation without a decrease in embolization effect in
      the normal swine kidney, and it also reduces the likelihood of venous thrombus
      formation.

PMID- 19164115
TI  - Pain and other side effects after MR arthrography: prospective evaluation in 1085
      patients.
AB  - PURPOSE: To prospectively evaluate pain and other side effects after magnetic
      resonance (MR) arthrography. MATERIALS AND METHODS: Institutional review board
      approval and patient informed consent were obtained. MR arthrography was
      performed in 1085 patients. In 1011 patients, 2 mmol/L gadopentetate dimeglumine
      was injected. In patients whose wrists were examined, 5 mmol/L gadoterate
      dimeglumine was injected. Pain was measured directly after injection, 4 hours
      after injection, 1 day [18-30 hours] after injection, and 1 week [6-8 days] after
      injection and compared with pain at baseline (before contrast material was
      injected). A visual analogue scale or verbal rating scale (score range, 0-10) was
      used to measure pain. When increased pain persisted at the end of the observation
      period, additional assessment was performed to exclude infection. Evaluated
      factors with a potential effect on pain were time after injection, joint type,
      contrast agent volume, patient age and sex, and radiologist experience. Repeated
      measures analysis of variance was used. RESULTS: Mean pain increase was most
      pronounced 4 hours after injection (P < .0001). This increase was most pronounced
      in the hip, followed by the elbow, knee, wrist, ankle, and shoulder. (Differences
      between joints were not significant [P = .26].) Pain scores returned to baseline
      levels 1 week after injection. Patients younger than 30 years had more pronounced
      pain than did patients in other age groups at all time points (P = .044). Joint
      type, contrast agent volume (P = .44), patient sex (P = .29), and radiologist
      experience (P = .10) did not significantly affect pain scores. No patient had
      infection or any other severe side effect. Besides joint pain, minor side effects
      included pressure, headache, muscle ache, swollen hand, fatigue, vertigo,
      increased blood glucose level, and pruritus. CONCLUSION: MR arthrography
      temporarily increases joint-related pain. Such pain depends on patient age but
      not on joint type, contrast material volume, patient sex, or radiologist
      experience.

PMID- 19164116
TI  - Positive predictive value of specific mammographic findings according to reader
      and patient variables.
AB  - PURPOSE: To evaluate the risk of cancer (positive predictive value [PPV])
      associated with specific findings (mass, calcifications, architectural
      distortion, asymmetry) in mammographic examinations with abnormal results, to
      determine the distribution of these findings in examinations in which the
      patients received a diagnosis of cancer and examinations in which the patients
      did not, and to analyze PPV variation according to radiologist and patient
      factors. MATERIALS AND METHODS: HIPAA-compliant institutional review board
      approval was obtained. PPV of mammographic findings was evaluated in a
      prospective cohort of 10,262 women who underwent 10,641 screening or diagnostic
      mammographic examinations with abnormal results between January 1998 and December
      2002 in the San Francisco Mammography Registry. The cohort was linked with the
      Surveillance Epidemiology and End Results program to determine cancer status
      among these women. PPVs were calculated for each finding and were stratified
      according to patient characteristics, cancer type, and radiologist reader.
      RESULTS: Cases of breast cancer (n = 1552) were identified (invasive, n = 1287;
      ductal carcinoma in situ, n = 270); in five, both kinds of breast cancer were
      recorded. Overall, of the number of interpretations, masses were most frequently
      noted in 56%, followed by calcifications in 29%, asymmetry in 12%, and
      architectural distortion in 4%. Masses, calcifications, architectural distortion,
      and developing asymmetry demonstrated similar PPVs in screening examinations
      (9.7%, 12.7%, 10.2%, and 7.4%, respectively), whereas one-view-only and focal
      asymmetry demonstrated lower PPVs (3.6% and 3.7%, respectively) and were a
      frequent reason for an abnormal result (42%). Overall, one (5%) in 20 invasive
      cancers was identified with asymmetry, one (6%) in 16 invasive cancers was
      identified with architectural distortion, one (21%) in five invasive cancers was
      identified with calcifications, and two (68%) in three invasive cancers were
      identified with a mass. CONCLUSION: Five percent of invasive cancers were
      identified with asymmetry, and asymmetry is more weakly associated with cancer in
      screening examinations than are mass, calcifications, and architectural
      distortion.

PMID- 19164117
TI  - Evaluation of off-the-shelf displays for use in the American Board of Radiology
      maintenance of certification examination.
AB  - PURPOSE: To prospectively compare high-, mid-, and low-resolution off-the-shelf
      displays currently employed by commercial testing centers, in terms of visibility
      of lesion features needed to render a diagnostic decision when possible diagnoses
      are provided in a multiple-choice format during a maintenance of certification
      (MOC) examination. MATERIALS AND METHODS: The Psychometrics Division of the
      American Board of Radiology (ABR) approved the studies (human subjects and HIPAA
      compliant). One study compared 1280 x 1024 displays with 1024 x 768 displays; the
      second, 1600 x 1200 with 1280 x 1024 displays. Images from nine subspecialties
      were used. In each study, observers viewed images twice-once on each display.
      Diagnoses were provided, and observers rated visibility of diagnostic features.
      RESULTS: Of 7977 data pairs analyzed in study 1, the 1024 and 1280 displays
      received the same ratings for 5726 data pairs (72% of the time), with the 1024
      display receiving a higher rating for 679 data pairs (9% of the time) and the
      1280 receiving a higher rating for 1572 data pairs (19% of the time) (P < .0001).
      When rating differences existed, all subspecialties except nuclear medicine had
      significantly more high-visibility ratings with the 1280 display. Of 1090 data
      pairs analyzed in study 2, the 1280 and 1600 displays received the same ratings
      for 689 data pairs (63% of the time), with the 1280 receiving a higher rating for
      162 data pairs (15% of the time) and the 1600 receiving a higher rating for 239
      data pairs (22% of the time) (P = .0001). When rating differences existed, only
      cardiopulmonary and musculoskeletal images had significantly more high-visibility
      ratings with the 1600 display. CONCLUSION: For the ABR MOC examinations, 1280 x
      1024 displays should be used, compared to 1024 x 768 displays; 1600 x 1200
      displays may be necessary for some images. Good-quality images must be used on
      the examinations, so digital rather than digitized film images should be used to
      ensure high-quality images.

PMID- 19164118
TI  - Extension of air into the right perirenal space after duodenal perforation: CT
      findings.
AB  - PURPOSE: To determine the extraperitoneal distribution of air following
      perforation of the second portion of the duodenum. MATERIALS AND METHODS:
      Institutional review board approval was obtained for this HIPAA-compliant study.
      The requirement for written informed consent was waived. Two reviewers who were
      aware of the presence of duodenal perforation after duodenal endoscopy
      retrospectively reviewed computed tomographic (CT) images in eight patients (one
      man, seven women; mean age, 68 years; age range, 27-88 years) to assess and
      categorize the location of extraluminal air. RESULTS: Extraluminal air was
      detected in the following locations: right anterior pararenal space (n = 8),
      right perirenal space (n = 7), right posterior pararenal space (n = 4), right
      properitoneal compartment (n = 4), bare area of the liver (n = 6), right
      extraperitoneal pelvis (n = 7), hepatoduodenal ligament (n = 3), mesentery (n =
      2), mediastinum (n = 4), portal venous system (n = 1), and peritoneal cavity (n =
      1). CONCLUSION: Air extended posteriorly into the right perirenal space in seven
      (88%) of eight patients following perforation of the second portion of the
      duodenum. Duodenal perforation introduces potential for direct communication
      between the right anterior pararenal space and the right perirenal space.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsnajnls.org/cgi/content/full/2503080605/DC1.

PMID- 19164119
TI  - Mild cognitive impairment and alzheimer disease: patterns of altered cerebral
      blood flow at MR imaging.
AB  - PURPOSE: To examine regional cerebral blood flow (rCBF) in incident mild
      cognitive impairment (MCI) and Alzheimer disease (AD) by using continuous
      arterial spin-labeling (CASL) magnetic resonance (MR) imaging. MATERIALS AND
      METHODS: This study was approved by the local institutional review board and was
      compliant with HIPAA regulations. Informed consent was obtained. rCBF was
      measured in 38 control subjects, 29 MCI patients, and 37 AD patients who were
      participating in a longitudinal epidemiologic study. Multisection CASL MR imaging
      with alternating single and double adiabatic inversion pulses and ramp-sampled
      echo-planar imaging were performed to acquire 19 contiguous axial sections. Voxel
      level rCBF was compared among groups by using an analysis of variance design;
      clusters of voxels with significant group differences were identified. Multiple
      regression models controlled for age, sex, and presence of hypertension and
      related the mean rCBF in those clusters to the presence of MCI and AD. RESULTS:
      MCI and AD patients had decreased rCBF in the posterior cingulate gyrus (P = .01)
      with extension to the medial precuneus compared with that in control subjects.
      MCI patients had increased rCBF in the left hippocampus (P < .001), right
      amygdala (P = .007), and rostral head of the right caudate nucleus and ventral
      putamen and globus pallidus (P = .003) compared with that in control subjects. AD
      patients had decreased rCBF relative to that in control subjects and MCI patients
      in the left inferior parietal (P = .005), left lateral frontal (P < .001), left
      superior temporal (P = .001), and left orbitofrontal (P = .003) cortices. AD
      patients had increased rCBF in the right anterior cingulate gyrus (P = .02)
      compared with that in control subjects. CONCLUSION: The transition from normal
      cognition to AD is associated with dynamic pathologic processes in the brain, and
      this is reflected by both decreases and increases in rCBF. Increases in rCBF
      suggest a cellular and vascular compensatory process associated with incipient
      AD. SUPPLEMENTAL MATERIAL:
      http://radiology.rsnajnls.org/cgi/content/full/2503080751/DC1.

PMID- 19164120
TI  - Existence of the diffusion-perfusion mismatch within 24 hours after onset of
      acute stroke: dependence on proximal arterial occlusion.
AB  - PURPOSE: To assess the existence of a mismatch between lesions on diffusion
      weighted (DW) and perfusion-weighted (PW) magnetic resonance (MR) images obtained
      within 24 hours after onset of acute stroke and to use mismatch data and
      angiographic evidence of proximal arterial occlusion (PAO) to investigate whether
      the existence of the mismatch depends on the existence of PAO. MATERIALS AND
      METHODS: In this institutional review board-approved, HIPAA-compliant study, 109
      retrospectively identified patients had undergone DW and PW imaging within 24
      hours of stroke onset. Relative mismatch was computed as the difference between
      lesion volumes on mean transit time maps and DW images, divided by DW lesion
      volume. Computed tomographic (CT) angiography or MR angiography distinguished
      patients with PAO (n = 68) from those with no PAO (NPAO; n = 41). Eligibility for
      hypothetical thrombolysis was assessed with two different criteria: (a) one
      derived from the successful Desmoteplase in Acute Ischemic Stroke Trial (DIAS)
      and Dose Escalation of Desmoteplase for Acute Ischemic Stroke Trial (DEDAS), and
      (b) another requiring 160% mismatch. RESULTS: Of the 109 patients, 77 (71%)
      satisfied the DIAS-DEDAS eligibility criteria, and 61 (56%) satisfied the 160%
      criterion. The NPAO patients demonstrated decreasing eligibility with increasing
      time after onset by using DIAS-DEDAS criteria (P = .015) and showed a similar
      trend with the 160% criterion (P = .078). The NPAO patients were less likely to
      be eligible after 9 hours than before 9 hours (17% for >9 hours vs 72% for <9
      hours with DIAS-DEDAS criteria, P = .002; and 8% for >9 hours vs 45% for <9 hours
      with 160% criterion, P = .033). However, PAO patients demonstrated a trend toward
      increasing eligibility with the DIAS-DEDAS criteria (P = .099) and no significant
      difference for after 9 hours versus before 9 hours (84% for >9 hours vs 78% for
      <9 hours with DIAS-DEDAS criteria, P = .742; and 68% for >9 hours vs 69% for <9
      hours with 160% criterion, P > .999). CONCLUSION: Persistence of mismatch after 9
      hours is common and occurs most often in patients with PAO.

PMID- 19164121
TI  - Comparison of 1.5- and 3.0-T MR imaging for evaluating the articular cartilage of
      the knee joint.
AB  - PURPOSE: To retrospectively compare the diagnostic performance of 1.5- and 3.0-T
      magnetic resonance (MR) imaging protocols for evaluating the articular cartilage
      of the knee joint in symptomatic patients. MATERIALS AND METHODS: This HIPAA
      compliant study was performed with a waiver of informed consent from the
      institutional review board. The study group consisted of 200 symptomatic patients
      undergoing MR examination of the knee at 1.5 T (61 men, 39 women; mean age, 38.9
      years) or 3.0 T (52 men, 48 women; mean age, 39.1 years), who also underwent
      subsequent arthroscopic knee surgery. All MR examinations consisted of
      multiplanar fast spin-echo sequences with similar tissue contrast at 1.5 and 3.0
      T. All articular surfaces were graded at arthroscopy by using the Noyes
      classification system. Three musculoskeletal radiologists retrospectively and
      independently graded all articular surfaces seen at MR imaging by using a similar
      classification system. The sensitivity, specificity, and accuracy of the 1.5- and
      3.0-T MR protocols for detecting cartilage lesions were determined by using
      arthroscopy as the reference standard. The z test was used to compare
      sensitivity, specificity, and accuracy values at 1.5 and 3.0 T. RESULTS: For all
      readers combined, the respective sensitivity, specificity, and accuracy of MR
      imaging for detecting cartilage lesions were 69.3%, 78.0%, and 74.5% at 1.5 T (n
      = 241) and 70.5%, 85.9%, and 80.1% at 3.0 T (n = 226). The MR imaging protocol
      had significantly higher specificity and accuracy (P < .05) but not higher
      sensitivity (P = .73) for detecting cartilage lesions at 3.0 T than at 1.5 T.
      CONCLUSION: A 3.0-T MR protocol has improved diagnostic performance for
      evaluating the articular cartilage of the knee joint in symptomatic patients when
      compared with a 1.5-T protocol.

PMID- 19164122
TI  - Assessing myometrial infiltration by endometrial cancer: uterine virtual
      navigation with three-dimensional US.
AB  - PURPOSE: To describe and analyze the diagnostic performance of uterine virtual
      navigation with three-dimensional (3D) ultrasonography (US) for the assessment of
      the depth of myometrial infiltration by endometrial cancer. MATERIALS AND
      METHODS: Institutional review board approval was obtained; patients gave oral
      informed consent. Women with endometrial cancer were evaluated by using 3D US
      prior to surgical staging. A 3D volume of the whole uterus was obtained and
      analyzed by using software. Virtual navigation through three orthogonal planes
      was performed to identify the shortest myometrial tumor-free distance to serosa
      (TDS) by analyzing the lateral, anterior, posterior, and fundal portions of the
      myometrium. Myometrial infiltration was also assessed by subjective impression of
      an examiner. Histologic findings of myometrial infiltration and TDS measured by a
      pathologist were used as the reference standard. A receiver operating
      characteristic curve was plotted to identify the best cutoff for TDS for
      identifying myometrial infiltration of 50% or more. RESULTS: Ninety-six women
      (mean age, 61.8 years; range, 31-86 years) with endometrial cancer were included
      in the study. At histologic analysis, myometrial invasion was found to be less
      than 50% in 69 (72%) cases and 50% or more in 27 (28%) cases. TDS measured with
      US was positively correlated with histologically measured TDS (r = 0.649; 95%
      confidence interval: 0.52, 0.76). The best cutoff for US-measured TDS was 9.0 mm
      (sensitivity, 100%; specificity, 61%; negative predictive value, 100%; positive
      predictive value, 50%). Subjective impression had a sensitivity of 92.6%, a
      specificity of 82.3%, a negative predictive value of 96.6%, and a positive
      predictive value of 67.7%. CONCLUSION: Uterine virtual navigation with 3D US is a
      reliable method for the assessment of myometrial infiltration in patients with
      endometrial cancer.

PMID- 19164123
TI  - Myocardial microinfarction after coronary microembolization in swine: MR imaging
      characterization.
AB  - PURPOSE: To use first-pass perfusion and delayed-enhanced (DE) magnetic resonance
      (MR) imaging for the detection of the early effects of coronary microembolization
      on myocardial perfusion and viability. MATERIALS AND METHODS: Approval was
      obtained from the institutional committee on animal research. A hybrid x-ray and
      MR imaging system was used to guide the endovascular catheter and quantify the
      left anterior descending coronary artery (LAD) perfusion territory before
      microembolization and ischemic myocardium and microinfarction after
      microembolization. The embolic agent was selectively delivered in the LAD in six
      pigs. First-pass perfusion MR imaging was performed 1 hour and 1 week after
      microembolization. Microinfarction was measured on DE MR images in beating and
      nonbeating hearts (high-spatial-resolution sequence) by using extracellular and
      blood pool MR contrast media and after death. The Wilcoxon signed rank test and
      correlation analysis were used. RESULTS: The LAD perfusion territory was 35% of
      left ventricular (LV) mass +/- 2 (standard error of the mean). Microembolization
      caused perfusion deficit in 15.7% of LV mass +/- 2.6 compared with that of LAD
      territory (P = .03). At 1 week, perfusion parameters improved and the extent of
      hypoperfused territory declined (4.6% of LV mass +/- 1.4, P = .03).
      Microinfarction size expanded from 1.4% of LV mass +/- 0.2 at 1 hour to 7.5% of
      LV mass +/- 1.2 at 1 week. In nonbeating hearts and at triphenyltetrazolium
      chloride staining at 1 week, microinfarction size was 7.6% of LV mass +/- 1.4 and
      7.2% of LV mass +/- 1.5, respectively. There was no correlation between the
      ejection fraction and the extents of microinfarction or hypoperfused territory.
      Histopathologic findings confirmed the presence of patchy microinfarction.
      CONCLUSION: Coronary microembolization caused persistent decline in myocardial
      perfusion at first-pass perfusion imaging. DE MR imaging has the potential to
      help reliably quantify subacute microinfarction. The magnitude of LV dysfunction
      is not related to the extents of microinfarction or hypoperfused territory.

PMID- 19164124
TI  - Acute pulmonary embolism: relationships between ground-glass opacification at
      thin-section CT and hemodynamics in pigs.
AB  - PURPOSE: To investigate the link between acute pulmonary embolism (PE) and
      occurrence of ground-glass opacity (GGO) and the relationships between this
      occurrence and hemodynamics in an animal model of acute PE. MATERIALS AND
      METHODS: In this animal care committee-approved study, PE was achieved by
      injecting blood clots through a central venous catheter in five pigs. Thin
      section computed tomography (CT) and hemodynamic measurements-mean pulmonary
      arterial pressure (Ppa), systemic and pulmonary cardiac outputs, effective
      pulmonary capillary pressure (Pc'), right atrial pressure, and occluded Ppa-were
      obtained before and after PE was achieved. Severity and extent of GGO were
      assigned scores subjectively, and lung attenuation was measured on each scan.
      Measurements were performed every 20 minutes after PE was achieved, for a total
      duration of 60 minutes. Finally, CT pulmonary angiography was performed. Lung
      attenuation was measured in unobstructed and obstructed zones. Measurements were
      compared by using analysis of variance and Student t test when appropriate.
      Correlations were investigated through Spearman rank correlation test. RESULTS:
      In the unobstructed lung zones, GGO appeared immediately after PE was achieved,
      with an increased mean lung attenuation (P < .001). Mean Ppa and Pc' increased
      immediately after PE was achieved, and Pc' reached 23 mm Hg, a value associated
      with pulmonary edema. Cardiac output did not change (P = .238). Lung attenuation
      and subjective score assignment for GGO were significantly correlated with Ppa
      and Pc' (P < .001 to .002). CONCLUSION: Acute PE induces GGO in unobstructed lung
      zones. Given constant cardiac output, GGO is likely to be related to
      redistribution of blood flow from obstructed to unobstructed lung zones and
      occurs at a pressure consistent with pulmonary edema.

PMID- 19164125
TI  - Reperfusion hemorrhage following acute myocardial infarction: assessment with T2*
      mapping and effect on measuring the area at risk.
AB  - Research ethics committee approval and informed consent were obtained. The
      purpose of this study was to assess the feasibility of multiecho T2* mapping of
      the heart for detecting reperfusion hemorrhage following percutaneous primary
      coronary intervention (PPCI) for acute myocardial infarction, and to measure the
      effect of hemorrhage on quantifying the ischemic area at risk (IAR) on T2
      weighted magnetic resonance images. Fifteen patients (mean age, 59 years; 13 men,
      two women) were imaged a mean of 3.2 days following PPCI. The mean area of
      hemorrhage, indicated by a T2* decay constant of less than 20 msec, was 5.0% +/-
      4.9 (standard deviation) at the level of the infarct and this correlated with the
      infarct (r(2) = 0.76, P < .01) and microvascular obstruction (r(2) = 0.75, P <
      .01) volumes. When 5% or less hemorrhage was present, the IAR was underestimated
      by 50% at a standard deviation threshold level of five, compared with a boundary
      detection tool (21.8% vs 44.0%, P < .05). T2* mapping is feasible for quantifying
      post-reperfusion hemorrhage and boundary detection is required to accurately
      assess the IAR when hemorrhage is present.

PMID- 19164126
TI  - The mechanism involved in the repression of the mu opioid receptor gene
      expression in CEM x174 cells infected by simian immunodeficiency virus.
AB  - Morphine can promote the pathogenesis of human acquired immunodeficiency syndrome
      through binding to the mu opioid receptor (MOR) in immune cells. Previous
      investigation has suggested that expression of the MOR gene in lymphocytes is
      triggered by cooperative interaction between transcription factors, specificity
      protein 1 (Sp1) and Ying Yang 1 (YY1), in the promoter region. However, the
      specific molecular mechanism by which immunodeficiency virus infection impacts
      regulation of the MOR gene expression in lymphocytes is still unclear. In this
      study, it was demonstrated that SIV (SIVmac239) infection may result in gradual
      reduction of the MOR gene expression and Sp1 during a period of 48 h
      postinfection by analysis of quantitative real-time RT-PCR and Western blotting.
      The results of methylation-specific PCR showed that two of 14 CpG islands
      adjacent to the Sp1 and YY1 elements in the promoter region were methylated,
      which together with reduced Sp1, contributed to the failure of interaction of Sp1
      with YY1 and their binding to the elements, as determined by
      coimmunoprecipitation, chromatin immunoprecipitation-real-time PCR, and EMSAs.
      The repression of the MOR gene secondary to SIVmac239 infection could be
      abolished by the demethylating agent 5-aza-2'-deoxycytidine. Transfection with
      Sp1-expressing vector (PN3-Sp1) was also able to enhance the activity of the
      promoter in SIVmac239-infected cells. We therefore concluded that aberrant
      methylation of the promoter and reduction of Sp1 resulting from SIVmac239
      infection led to the silencing of the MOR gene. This finding will be helpful in
      understanding the synergistic mechanism of HIV infection and morphine addiction
      in the pathogenesis of AIDS.

PMID- 19164127
TI  - TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic
      cell maturation.
AB  - Dendritic cells (DCs) play an important role in bridging innate and adaptive
      immunity. These APCs have the ability to recognize specific molecular signatures
      of pathogens through TLRs. In particular, the intracellular TLR7 and TLR8,
      mediating the recognition of ssRNA by DCs, play a major role in the immune
      response during viral infection. Although differences have been identified
      between TLR7 and TLR8, in terms of cellular expression and functions, the
      signaling pathways that lead to DC maturation following TLR7 or TLR8 engagement
      are largely unknown. We compared the signaling pathways involved in human CD34-DC
      maturation induced by agonists selective for TLR7 (imiquimod) or TLR8 (3M002).
      TLR7 and TLR8 activation up-regulated CCR7, CD40, CD86, and CD83 expression and
      IL-6 and IL-12p40 production. However, only TLR8 activation led to IL-12p70
      production and il-12p35 mRNA expression. We found that upon TLR7 and TLR8
      activation, JNK and NF-kappaB positively regulated the expression of CCR7, CD86,
      CD83, and CD40 and the production of IL-6 and IL-12p40. However, although p38MAPK
      participated in the up-regulation of maturation markers in response to TLR7
      activation, this kinase exerted an inhibitory effect on CD40 expression and IL-12
      production in TLR8-stimulated DCs. We also showed that the Jak/STAT signaling
      pathway was involved in CD40 expression and cytokine production in TLR7
      stimulated DCs but negatively regulated CD83 expression and cytokine secretion in
      DCs activated through TLR8. This study showed that TLR7 and TLR8 activate similar
      signaling pathways that play different roles in DC maturation, depending on which
      TLR is triggered.

PMID- 19164128
TI  - Multiple signaling pathways contribute to synergistic TLR ligand-dependent
      cytokine gene expression in human monocyte-derived macrophages and dendritic
      cells.
AB  - TLRs are innate immune receptors that recognize pathogen-associated structures.
      Binding of ligands to different TLRs can induce the production of proinflammatory
      cytokines in a synergistic manner. We have analyzed the molecular mechanisms of
      synergy in TLR ligand-stimulated human monocyte-derived macrophages and dendritic
      cells (moDCs). Stimulation of moDCs with the TLR8 ligand together with the TLR3
      or TLR4 ligand led to synergistic IL-6, IL-10, IL-12, and TNF-alpha mRNA
      expression and cytokine production. DNA-binding assays showed that TLR3 and TLR8
      stimulation induced binding of multiple IFN regulatory factor (IRF) and STAT
      transcription factors to the IL-12p35 gene promoter IFN-stimulated response
      element in moDCs and macrophages but with different binding profiles and
      kinetics. We also demonstrate that NF-kappaB, MAPKs and PI-3K pathways have an
      important role in TLR-induced cytokine gene expression, as pharmacological
      inhibitors of these signaling pathways inhibited TLR3, TLR4, and TLR8 ligand
      induced cytokine mRNA expression and protein production. Especially, synergistic
      IL-12p70 production was abolished completely in NF-kappaB, MAPK p38, and PI-3K
      inhibitor-treated moDCs. Our data suggest that TLR-dependent, synergistic
      cytokine gene expression results from enhanced activation and cooperation among
      NF-kappaB, IRF, MAPK, PI-3K, and STAT signaling pathways.

PMID- 19164129
TI  - Crucial implication of protein kinase C (PKC)-delta, PKC-zeta, ERK-1/2, and p38
      MAPK in migration of human asthmatic eosinophils.
AB  - Asthma is associated with an eosinophil infiltration into the bronchial mucosa. 5
      Oxo-6,8,11,14(E,Z,Z,Z)-eicosatetraenoic acid (5-oxo-ETE), a potent eosinophil
      chemotactic factor, activates cell motility, adherence, and proteolysis, notably,
      by promoting CD11b expression, matrix metalloproteinase (MMP)-9 secretion, and
      plasmin generation. We investigated the intracellular signaling pathways
      implicated in these various steps by using different, selective inhibitors. Human
      eosinophil migration through a reconstituted basement membrane in response to 5
      oxo-ETE was greatly inhibited (>or=72%) by the protein kinase C (PKC)-delta, PKC
      zeta, ERK-1/2, and p38 inhibitors. Our findings indicate that PKC-delta mediates
      cell motility, CD11b expression, and MMP-9 granule release. PKC-zeta is also
      largely involved in eosinophil migration, although its specific targets remain
      undefined. ERK-1/2 and p38 modulate CD11b expression; ERK-1/2 is also involved in
      long-term MMP-9 secretion and p38 in the plasmin activation system. We
      demonstrated the crucial implication of PKC-delta, PKC-zeta, ERK-1/2, and p38 in
      human blood eosinophil migration through extracellular matrix components.
      Targeting specific pathways may have therapeutic potential for the treatment of
      allergic airway inflammation.

PMID- 19164130
TI  - ATP induces P2X7 receptor-independent cytokine and chemokine expression through
      P2X1 and P2X3 receptors in murine mast cells.
AB  - Extracellular ATP mediates a diverse array of biological responses in many cell
      types and tissues, including immune cells. We have demonstrated that ATP induces
      purinergic receptor P2X(7) mediated membrane permeabilization, apoptosis, and
      cytokine expression in murine mast cells (MCs). Here, we report that MCs
      deficient in the expression of the P2X(7) receptor are resistant to the ATP
      induced membrane permeabilization and apoptosis. However, ATP affects the
      tyrosine phosphorylation pattern of P2X(7)knockout cells, leading to the
      activation of ERK1/2. Furthermore, ATP induces expression of several cytokines
      and chemokines in these cells, including IL-4, IL-6, IFN-gamma, TNF-alpha,
      RANTES, and MIP-2, at the mRNA level. In addition, the release of IL-6 and IL-13
      to cell-conditioned medium was confirmed by ELISA. The ligand selectivity and
      pharmacological profile indicate the involvement of two P2X family receptors,
      P2X(1) and P2X(3). Thus, depending on genetic background, particular tissue
      microenvironment, and ATP concentration, MCs can presumably engage different P2X
      receptor subtypes, which may result in functionally distinct biological responses
      to extracellular nucleotides. This finding highlights a novel level of complexity
      in the sophisticated biology of MCs and may facilitate the development of new
      therapeutic approaches to modulate MC activities.

PMID- 19164131
TI  - Making all the children above average: ethical and regulatory concerns for
      pediatricians in pediatric enhancement research.
AB  - Building on the knowledge generated by the long history of disease-oriented
      research, the next few decades will witness an explosion of biomedical
      enhancements to make people faster, stronger, smarter, less forgetful, happier,
      prettier, and live longer. Growing interest in pediatric enhancements is likely
      to stimulate the conduct of enhancement research involving children. However,
      guidelines for the protection of human subjects were developed for investigations
      of therapeutic modalities. To date, virtually no attention has been paid to
      whether these rules would be appropriate for investigations to establish the
      safety and efficacy of technologies intended for enhancement rather than
      therapeutic uses and, if not, whether ethically acceptable rules could be
      designed. This article discusses whether the current guidelines for pediatric
      research provide appropriate protections for pediatric subjects in enhancement
      research and considers what additional protections might be necessary.

PMID- 19164132
TI  - Independent risk factors for beach-related injuries in children.
AB  - This study was conducted in a resort area during the summer tourist season to
      identify independent risk factors for injuries to children in a beach
      environment. Surveys including demographics, environmental and beach conditions,
      group characteristics, and hypothesized risk factors were administered to 28
      cases and 105 controls. The most common injuries were lacerations and puncture
      wounds, followed by musculoskeletal injuries. The following environmental factors
      were found to significantly increase the risk for pediatric beach-related injury:
      rough/choppy water, cloudy weather, greater than 3 children in the group,
      participation by the child in water safety classes, and use of beach equipment
      (including boogie boards, skim boards, and kayaks). Providers who care for
      children can use this information to educate parents about beach safety. Targeted
      interventions that address these risk factors may reduce injuries sustained by
      children in a beach environment.

PMID- 19164133
TI  - Physician communication regarding cost when prescribing asthma medication to
      children.
AB  - Children with asthma require multiple medications, and cost may be a barrier to
      care. The purpose of this study was to determine how often physicians ask about
      cost when prescribing new asthma medication and to identify factors influencing
      queries. We surveyed pediatricians and family physicians and asked whether they
      asked about cost when prescribing new asthma medication and if cost was a barrier
      to prescribing. One third of physicians (35%) reported that concern for cost to
      the family was a barrier to prescribing. Half reported not asking their patients
      about drug costs. Pediatricians were less likely to ask about cost (odds ratio
      [OR] = 0.43; 95% confidence interval [CI] = 0.20-0.92) when compared with family
      physicians. For every 10% increase in the number of privately insured patients, a
      physician was less likely to ask about cost (OR = 0.83; 95% CI = 0.74-0.94).
      Communication about medication costs should be included in childhood asthma
      management.

PMID- 19164134
TI  - Translating an evidence-based intervention for pediatric overweight to a primary
      care setting.
AB  - The objective of this study was to train pediatric providers to address weight,
      body mass index (BMI), diet, and physical activity with parents. Children aged 8
      to 12 years with BMI of >or=85th percentile were eligible if accompanied by a
      parent. The intervention was a family-based, 11-session behavioral program
      focusing on healthy eating and physical activity. Outcome measures were weight
      and BMI. Seventy-three child-parent dyads enrolled. Children who attended at
      least 6 of 8 intervention sessions and 1 of 3 follow-up sessions (completers)
      lost an average of 2.84 lb; change in BMI z scores was statistically significant
      at 5 months (P < .001). Primary care providers can acquire skills to increase
      their confidence in approaching children and parents regarding weight and BMI.
      Parents and children will attend an intervention targeting healthy weight in the
      pediatric practice. Professional office staff can be trained to provide an
      evidence-informed intervention that promotes healthy weight.

PMID- 19164135
TI  - REM sleep behavior disorder and the risk of developing Parkinson disease or
      dementia.

PMID- 19164136
TI  - Another year ... Another top 10 list.

PMID- 19164137
TI  - Universal access to antiretroviral therapy: are we moving the targets?

PMID- 19164138
TI  - No residual activity of raltegravir after development of 148 complex mutations in
      vivo.

PMID- 19164139
TI  - The lipopeptide antibiotic Friulimicin B inhibits cell wall biosynthesis through
      complex formation with bactoprenol phosphate.
AB  - Friulimicin B is a naturally occurring cyclic lipopeptide, produced by the
      actinomycete Actinoplanes friuliensis, with excellent activity against gram
      positive pathogens, including multidrug-resistant strains. It consists of a
      macrocyclic decapeptide core and a lipid tail, interlinked by an exocyclic amino
      acid. Friulimicin is water soluble and amphiphilic, with an overall negative
      charge. Amphiphilicity is enhanced in the presence of Ca(2+), which is also
      indispensable for antimicrobial activity. Friulimicin shares these
      physicochemical properties with daptomycin, which is suggested to kill gram
      positive bacteria through the formation of pores in the cytoplasmic membrane. In
      spite of the fact that friulimicin shares features of structure and potency with
      daptomycin, we found that friulimicin has a unique mode of action and severely
      affects the cell envelope of gram-positive bacteria, acting via a defined target.
      We found friulimicin to interrupt the cell wall precursor cycle through the
      formation of a Ca(2+)-dependent complex with the bactoprenol phosphate carrier
      C(55)-P, which is not targeted by any other antibiotic in use. Since C(55)-P also
      serves as a carrier in teichoic acid biosynthesis and capsule formation, it is
      likely that friulimicin blocks multiple pathways that are essential for a
      functional gram-positive cell envelope.

PMID- 19164140
TI  - Occurrence of efflux mechanism and cephalosporinase variant in a population of
      Enterobacter aerogenes and Klebsiella pneumoniae isolates producing extended
      spectrum beta-lactamases.
AB  - We investigated the occurrence of multidrug resistance in 44 Enterobacter
      aerogenes and Klebsiella pneumoniae clinical isolates. Efflux was involved in
      resistance in E. aerogenes isolates more frequently than in K. pneumoniae
      isolates (100 versus 38% of isolates) and was associated with the expression of
      phenylalanine arginine beta-naphthylamide-susceptible active efflux. AcrA-TolC
      overproduction in E. aerogenes isolates was noted. An analysis of four E.
      aerogenes isolates for which cefepime MICs were high revealed no modification in
      porin expression but a new specific mutation in the AmpC beta-lactamase.

PMID- 19164141
TI  - Efficacy of ciprofloxacin in an experimental model of Escherichia coli
      chorioamnionitis in rabbits.
AB  - Pregnant rabbits were treated with ciprofloxacin alone or with gentamicin in a
      model of Escherichia coli chorioamnionitis, and the results were compared with
      those for untreated rabbits. The survival rate increased and the bacteremia
      decreased significantly in treated fetuses in comparison to controls (P = 0.003).
      Nevertheless, rapid selection of resistant mutants is a major limit to
      ciprofloxacin applications.

PMID- 19164142
TI  - Two clinical strains of Klebsiella pneumoniae carrying plasmid-borne blaIMP-4,
      blaSHV-12, and armA isolated at a Pediatric Center in Shanghai, China.
AB  - Two cases of pulmonary infection due to strains of multidrug-resistant Klebsiella
      pneumoniae were investigated. Beta-lactamase determinants, such as bla(IMP-4) and
      bla(SHV-12), and the 16S rRNA methyltransferase-encoding gene armA were detected
      in these plasmid-bearing organisms. The integron-borne bla(IMP-4) and armA
      contained intervening sequences highly related to those of a Vibrio cholerae O139
      plasmid found in Hangzhou, China.

PMID- 19164143
TI  - Permeation of chlorhexidine from alcoholic and aqueous solutions within excised
      human skin.

PMID- 19164144
TI  - Beta-lactam and fluoroquinolone combination antibiotic therapy for bacteremia
      caused by gram-negative bacilli.
AB  - The role of combination antibiotic therapy with a beta-lactam and a
      fluoroquinolone for bacteremia caused by gram-negative bacilli, to our knowledge,
      has not been previously described. Much of the previous study of combination
      therapy has included beta-lactams and aminoglycosides. We conducted a large
      retrospective cohort study to evaluate 28-day all-cause mortality in patients
      with monomicrobial bacteremia due to aerobic gram-negative bacilli who received
      either a combination of beta-lactams and fluoroquinolones or beta-lactam
      monotherapy. We enrolled adult patients admitted to Mayo Clinic hospitals from 1
      January 2001 to 31 October 2006 in the study. After stratification of patients by
      Pitt bacteremia scores, we used Cox regression models to estimate the hazard
      ratios (HR) for 28-day all-cause mortality after adjusting for the propensity to
      receive combination therapy. We identified 398 and 304 unique patients with
      bacteremia caused by gram-negative bacilli who received single and combination
      antibiotic therapy, respectively. In less severely ill patients with Pitt
      bacteremia scores of <4, combination therapy was associated with lower 28-day
      mortality than single therapy (4.2% [9 of 214] versus 8.8% [28 of 319]; adjusted
      HR, 0.44; 95% confidence interval [CI], 0.20 to 0.98; P = 0.044). In critically
      ill patients with Pitt bacteremia scores of >or=4, there was no difference in 28
      day mortality between combination and single therapy (25.6% [23 of 90] versus
      27.8% [22 of 79]; adjusted HR, 0.87; 95% CI, 0.47 to 1.62; P = 0.660). These
      findings were consistent for 14-day all-cause mortality. In this large cohort, we
      found for the first time that combination therapy with beta-lactams and
      fluoroquinolones was associated with a reduction in 28-day all-cause mortality
      among less severely ill patients with bacteremia caused by gram-negative bacilli.

PMID- 19164145
TI  - Temporal appearance of plasmid-mediated quinolone resistance genes.
AB  - One hundred fifty AAC(6')-Ib-positive gram-negative isolates collected between
      1981 and 1991 were examined by PCR for the presence of the aac(6')-Ib-cr variant
      and other plasmid-mediated quinolone resistance (PMQR) genes. None had the
      aac(6')-Ib-cr variant, qnrA, qnrS, qnrC, or qepA, but two strains collected in
      1988 had qnrB alleles, making these the earliest known PMQR genes.

PMID- 19164146
TI  - Transcriptional signature following inhibition of early-stage cell wall
      biosynthesis in Staphylococcus aureus.
AB  - To facilitate mode of action studies on antibacterial inhibitors of early-stage
      cell wall biosynthesis (CWB), we determined the transcriptional response of
      Staphylococcus aureus to depletion/inhibition of enzymes in this pathway by DNA
      microarray analysis. We identified a transcriptional signature distinct from that
      previously observed following exposure to inhibitors of late-stage CWB.

PMID- 19164147
TI  - Molecular epidemiology of outbreak-related pseudomonas aeruginosa strains
      carrying the novel variant blaVIM-17 metallo-beta-lactamase gene.
AB  - A study was designed to investigate the molecular epidemiological characteristics
      of multidrug-resistant outbreak-related Pseudomonas aeruginosa isolates collected
      in a university hospital in northern Greece. Of 29 nonreplicate P. aeruginosa
      isolates resistant to carbapenems and ceftazidime, 14 were positive for metallo
      beta-lactamase production. PCR analyses with primers specific for bla(VIM) and
      bla(IMP) revealed that 13 isolates carried a novel bla(VIM-2) gene variant,
      designated bla(VIM-17), and only 1 isolate carried bla(VIM-2), a gene predominant
      among P. aeruginosa strains in Greek hospitals. Pulsed-field gel electrophoresis
      of XbaI-digested genomic DNAs showed a close genetic relationship for 12 of 13
      bla(VIM-17)-carrying outbreak-related isolates, which were of the O11 serotype;
      the clonally unrelated isolate carrying bla(VIM-17) was of the O12 serotype. PCR
      mapping strategies for the detection of class 1 integrons and sequencing
      approaches revealed the presence of integrons containing one bla(VIM) cassette
      flanked by two aacA29 cassettes. These integrons were similar but not identical
      to In59 (GenBank accession number AF263519) initially described in France. All
      isolates carrying bla(VIM-17), regardless of their genetic profile, had an
      identical integron, named In59.3, indicating that although the hospital outbreak
      was mainly due to clonal dissemination, the horizontal transmission of the
      bla(VIM-17)-containing integron among P. aeruginosa isolates should also have
      occurred. An outbreak-related isolate and a control strain, both of which carried
      the bla(VIM-2) gene but which were clonally distinct, had an identical integron,
      named In59.2, which differed only at the level of the bla(VIM) gene from In59.3
      integrons, suggesting a common ancestry. The spread of the bla(VIM-17)-containing
      integron in clonally unrelated P. aeruginosa isolates without any evidence of
      plasmid carriage is probably associated with a transposon.

PMID- 19164148
TI  - Use of a surface plasmon resonance method to investigate antibiotic and plasma
      protein interactions.
AB  - The pharmacologic effect of an antibiotic is directly related to its unbound
      concentration at the site of infection. Most commercial antibiotics have been
      selected in part for their low propensity to interact with serum proteins. These
      nonspecific interactions are classically evaluated by measuring the MIC in the
      presence of serum. As higher-throughput technologies tend to lose information,
      surface plasmon resonance (SPR) is emerging as an informative medium-throughput
      technology for hit validation. Here we show that SPR is a useful automatic tool
      for quantification of the interaction of model antibiotics with serum proteins
      and that it delivers precise real-time kinetic data on this critical parameter.

PMID- 19164149
TI  - Amiodarone destabilizes intracellular Ca2+ homeostasis and biosynthesis of
      sterols in Leishmania mexicana.
AB  - Leishmaniasis represents a serious public health problem worldwide. The first
      line of treatment is based on glucantime and pentostan, which generate toxic
      effects in treated patients. We have recently shown that amiodarone, frequently
      used as an antiarrhythmic, possesses activity against Trypanosoma cruzi through
      the disruption of mitochondrial Ca(2+) homeostasis and the inhibition of parasite
      ergosterol biosynthesis, specifically at the level of oxidosqualene cyclase
      activity (G. Benaim, J. Sanders, Y. Garcia-Marchan, C. Colina, R. Lira, A.
      Caldera, G. Payares, C. Sanoja, J. Burgos, A. Leon-Rossell, J. Concepcion, A.
      Schijman, M. Levin, E. Oldfield, and J. Urbina, J. Med. Chem. 49:892-899, 2006).
      Here we show that at therapeutic concentrations, amiodarone has a profound effect
      on the viability of Leishmania mexicana promastigotes. Additionally, its effect
      on the viability of the parasite was greater against intracellular amastigotes
      than against promastigotes, and it did not affect the host cell. Using
      fluorimetric and confocal microscopy techniques, we also demonstrated that the
      mechanism of action of amiodarone was related to the disruption of intracellular
      Ca(2+) homeostasis through a direct action not only on the mitochondria but also
      on the acidocalcisomes. On the other hand, analysis of the free sterols in
      promastigotes incubated with amiodarone showed that this drug also affected the
      biosynthesis of 5-dehydroepisterol, which results in squalene accumulation, thus
      suggesting that amiodarone inhibits the squalene epoxidase activity of the
      parasite. Taken together, the results obtained in the present work point to a
      more general effect of amiodarone in trypanosomatids, opening potential
      therapeutic possibilities for this infectious disease.

PMID- 19164150
TI  - Plasmodium falciparum pfmdr1 amplification, mefloquine resistance, and parasite
      fitness.
AB  - Mefloquine is widely used in combination with artemisinin derivatives for the
      treatment of falciparum malaria. Mefloquine resistance in Plasmodium falciparum
      has been related to increased copy numbers of multidrug-resistant gene 1
      (pfmdr1). We studied the ex vivo dynamics of pfmdr1 gene amplification in culture
      adapted P. falciparum in relation to mefloquine resistance and parasite fitness.
      A Thai P. falciparum isolate (isolate TM036) was assessed by the use of multiple
      genetic markers as a single genotype. Resistance was selected by exposure to
      stepwise increasing concentrations of mefloquine up to 30 ng/ml in continuous
      culture. The pfmdr1 gene copy numbers increased as susceptibility to mefloquine
      declined (P = 0.03). No codon mutations at positions 86, 184, 1034, 1042, and
      1246 in the pfmdr1 gene were detected. Two subclones of selected parasites
      (average copy numbers, 2.3 and 3.1, respectively) showed a fitness disadvantage
      when they were grown together with the original parasites containing a single
      pfmdr1 gene copy in the absence of mefloquine; the multiplication rates were 6.3%
      and 8.7% lower, respectively (P < 0.01). Modeling of the dynamics of the pfmdr1
      copy numbers over time in relation to the relative fitness of the parasites
      suggested that net pfmdr1 gene amplification from one to two copies occurs once
      in every 10(8) parasites and that amplification from two to three copies occurs
      once in every 10(3) parasites. pfmdr1 gene amplification in P. falciparum is a
      frequent event and confers mefloquine resistance. Parasites with multiple copies
      of the pfmdr1 gene have decreased survival fitness in the absence of drug
      pressure.

PMID- 19164151
TI  - Lack of allergic cross-reactivity between fluconazole and voriconazole.

PMID- 19164152
TI  - Genetic analysis of factors affecting susceptibility of Bacillus subtilis to
      daptomycin.
AB  - Daptomycin is the first of a new class of cyclic lipopeptide antibiotics used
      against multidrug-resistant, gram-positive pathogens. The proposed mechanism of
      action involves disruption of the functional integrity of the bacterial membrane
      in a Ca(2+)-dependent manner. We have used transcriptional profiling to
      demonstrate that treatment of Bacillus subtilis with daptomycin strongly induces
      the lia operon including the autoregulatory LiaRS two-component system
      (homologous to Staphylococcus aureus VraSR). The lia operon protects against
      daptomycin, and deletion of liaH, encoding a phage-shock protein A (PspA)-like
      protein, leads to threefold increased susceptibility. Since daptomycin interacts
      with the membrane, we tested mutants with altered membrane composition for
      effects on susceptibility. Deletion mutations of mprF (lacking lysyl
      phosphatidylglycerol) or des (lipid desaturase) increased daptomycin
      susceptibility, whereas overexpression of MprF decreased susceptibility.
      Conversely, depletion of the cell for the anionic lipid phosphatidylglycerol led
      to increased resistance. Fluorescently labeled daptomycin localized to the septa
      and in a helical pattern around the cell envelope and was delocalized upon the
      depletion of phosphatidylglycerol. Together, these results indicate that the
      daptomycin-Ca(2+) complex interacts preferentially with regions enriched in
      anionic phospholipids and leads to membrane stresses that can be ameliorated by
      PspA family proteins.

PMID- 19164153
TI  - In vitro activity of Isavuconazole against Aspergillus species and zygomycetes
      according to the methodology of the European Committee on Antimicrobial
      Susceptibility Testing.
AB  - We evaluated the MICs of isavuconazole (ISAV) against 96 isolates of Aspergillus
      species and 36 zygomycetes according to the methodology of the European Committee
      on Antimicrobial Susceptibility Testing. In addition, the in vitro activity was
      obtained for hyphal inocula. ISAV exhibited good antifungal activity against the
      tested isolates with the exception of Aspergillus niger and Mucorales. The in
      vitro activity of ISAV was comparable to that of voriconazole aside from
      Mucorales.

PMID- 19164154
TI  - Pharmacokinetics of amoxicillin in maternal, umbilical cord, and neonatal sera.
AB  - The pharmacokinetics of amoxicillin were studied in umbilical cord and neonatal
      sera relative to maternal concentrations in prevention of neonatal group B
      streptococcus infection. The subjects were 44 pregnant women receiving
      amoxicillin as 1 or 2 g as an intravenous infusion. To measure the
      concentrations, blood samples were obtained from the mother, the arterial and
      venous umbilical cord, and the neonate. The pharmacokinetics were characterized
      by a five-compartment model by using nonlinear mixed-effects (population)
      modeling. The population estimates for the clearance, central volume of
      distribution, and the two peripheral maternal volumes of distribution were 19.7
      +/- 0.99 liters/h, 6.40 +/- 0.61 liters, and 5.88 +/- 0.83 liters (mean +/-
      standard error), respectively. The volume of distribution of the venous umbilical
      cord and the neonatal volume of distribution were 3.40 liters and 11.9 liters,
      respectively. The pharmacokinetic parameter estimates were used to simulate the
      concentration-time profiles in maternal, venous umbilical cord, and neonatal
      sera. The peak concentration in the venous umbilical cord serum was 18% of the
      maternal peak concentration. It was reached 3.3 min after the maternal peak
      concentration. The concentration-time profile in neonatal serum was determined by
      the profile in venous umbilical cord serum, which in turn depended on the profile
      in maternal serum. Furthermore, the simulated concentrations in maternal, venous
      umbilical cord, and neonatal sera exceeded the MIC for group B streptococcus for
      more than 90% of the 4-h dosing interval. In a first approximation, the 2-g
      infusion to the mother appears to be adequate for the prevention of group B
      streptococcal disease. However, to investigate the efficacy of the prophylaxis,
      further studies of the interindividual variability in pharmacokinetics are
      indicated.

PMID- 19164155
TI  - Distinct mode of interaction of a novel ketolide antibiotic that displays
      enhanced antimicrobial activity.
AB  - Ketolides represent the latest generation of macrolide antibiotics, displaying
      improved activities against some erythromycin-resistant strains, while
      maintaining their activity against erythromycin-susceptible ones. In this study,
      we present a new ketolide, K-1325, that carries an alkyl-aryl side chain at C-13
      of the lactone ring. According to our genetic and biochemical studies, K-1325
      binds within the nascent polypeptide exit tunnel, at a site previously described
      as the primary attachment site of all macrolide antibiotics. Compared with
      telithromycin, K-1325 displays enhanced antimicrobial activity against wild-type
      Escherichia coli strains, as well as against strains bearing the U2609C mutation
      in 23S rRNA. Chemical protection experiments showed that the alkyl-aryl side
      chain of K-1325 interacts specifically with helix 35 of 23S rRNA, a fact leading
      to an increased affinity of U2609C mutant ribosomes for the drug and
      rationalizing the enhanced effectiveness of this new ketolide.

PMID- 19164156
TI  - Engineered Streptomyces platensis strains that overproduce antibiotics
      platensimycin and platencin.
AB  - Platensimycin, which is isolated from Streptomyces platensis MA7327, and
      platencin, which is isolated from S. platensis MA7339, are two recently
      discovered natural products that serve as important antibiotic leads. Here we
      report on the identification of S. platensis MA7327 as a dual producer of both
      platensimycin and platencin. A PCR-based approach was used to locate and clone
      the locus involved in platensimycin and platencin production, including ptmR1,
      which encodes a putative GntR-like transcriptional regulator. Deletion of this
      gene from the producing organism allowed us to isolate strains that overproduce
      platensimycin and platencin with yields of 323 +/- 29 mg/liter and 255 +/- 30
      mg/liter, respectively. These results illustrate the effectiveness of genetic
      manipulation for the rational engineering of improvements in titers.

PMID- 19164157
TI  - Daptomycin versus Friulimicin B: in-depth profiling of Bacillus subtilis cell
      envelope stress responses.
AB  - The related lipo(depsi)peptide antibiotics daptomycin and friulimicin B show
      great potential in the treatment of multiply resistant gram-positive pathogens.
      Applying genome-wide in-depth expression profiling, we compared the respective
      stress responses of Bacillus subtilis. Both antibiotics target envelope
      integrity, based on the strong induction of extracytoplasmic function sigma
      factor-dependent gene expression. The cell envelope stress-sensing two-component
      system LiaRS is exclusively and strongly induced by daptomycin, indicative of
      different mechanisms of action in the two compounds.

PMID- 19164167
TI  - Wnt genes in the mouse uterus: potential regulation of implantation.
AB  - Wnt genes are involved in critical developmental and growth processes. The
      present study comprehensively analyzed temporal and spatial alterations in Wnt
      and Fzd gene expression in the mouse uterus during peri-implantation of
      pregnancy. Expression of Wnt4, Wnt5a, Wnt7a, Wnt7b, Wnt11, Wnt16, Fzd2, Fzd4, and
      Fzd6 was detected in the uterus during implantation. Wnt4 mRNA was most abundant
      in the decidua, whereas Wnt5a mRNA was restricted to the mesometrial decidua
      during decidualization. Wnt7a, Wnt7b, and Wnt11 mRNAs were abundantly detected in
      the endometrial epithelia. The expression of Wnt7b was robust in the luminal
      epithelium (LE) at the implantation site on Gestational Day 5, whereas Wnt11 mRNA
      disappeared in the LE adjacent to the embryo in the antimesometrial implantation
      chamber but remained abundant in the LE. Wnt16 mRNA was localized to the stroma
      surrounding the LE on Day 4 and remained in the stroma adjacent to the LE but not
      in areas undergoing the decidual reaction. Fzd2 mRNA was detected in the decidua,
      Fzd4 mRNA was in the vessels and stroma surrounding the embryo, and Fzd6 mRNA was
      observed in the endometrial epithelia, stroma, and some blood vessels during
      implantation. Ovarian steroid hormone treatment was found to regulate Wnt genes
      and Fzd receptors in ovariectomized mice. Especially, single injections of
      progesterone stimulated Wnt11 mRNA, and estrogen stimulated Wnt4 and Wnt7b. The
      temporal and spatial alterations in Wnt genes likely play a critical role during
      implantation and decidualization in mice.

PMID- 19164168
TI  - Bisphenol A effects on the growing mouse oocyte are influenced by diet.
AB  - Growing evidence suggests that exposure to bisphenol A (BPA) has the ability to
      disrupt several different stages of oocyte development. To date, most attention
      has focused on the effects of BPA on the periovulatory oocyte, and considerable
      variation is evident in the results of these studies. In our own laboratory,
      variation in the results of BPA studies conducted at different times appeared to
      correlate with changes in mill dates of animal feed. This observation, coupled
      with reports by others that dietary estrogens in feed are a confounding variable
      in studies of endocrine-disrupting chemicals, prompted us to evaluate the effect
      of diet on the results of BPA studies of the periovulatory oocyte. Genetically
      identical females were placed on a high- or low-phytoestrogen diet prior to
      mating. Their female offspring were exposed to BPA, oocytes collected, and
      meiotic spindle and chromosome characteristics compared between control and BPA
      treated females. We observed significant diet-related variation in both the
      frequency of abnormalities in oocytes from untreated females and in the response
      to BPA. Our results demonstrate that the impact of BPA on meiosis depends, at
      least in part, on diet. We suggest that variation in the conclusions of recent
      BPA studies reflects differences in the diets used, as well as other
      methodological differences. Because meiotic disturbances are a feature of all
      studies to date, however, we conclude that low levels of BPA adversely affect the
      meiotic process.

PMID- 19164169
TI  - Seminal fluid drives expansion of the CD4+CD25+ T regulatory cell pool and
      induces tolerance to paternal alloantigens in mice.
AB  - T regulatory (Treg) cells are implicated in maternal immune tolerance of the
      conceptus at implantation; however, the antigenic and regulatory signals
      controlling Treg cells in early pregnancy are undefined. To examine the role of
      male seminal fluid in tolerance induction, the effect of exposure to seminal
      fluid at mating on responsiveness to paternal alloantigens was examined using
      paternal tumor cell grafts and by delayed-type hypersensitivity (DTH) challenge
      on Day 3.5 postcoitum. Exposure to seminal fluid inhibited rejection of paternal
      tumor cells, independently of fertilization and embryo development, while seminal
      fluid from major histocompatability complex (MHC)-dissimilar males was less
      effective. Similarly, mating with intact males suppressed the DTH response to
      paternal alloantigens in an MHC-specific fashion. Excision of the seminal vesicle
      glands diminished the tolerance-inducing activity of seminal fluid. Mating with
      intact males caused an increase in CD4(+)CD25(+) cells expressing FOXP3 in the
      para-aortic lymph nodes draining the uterus, beyond the estrus-associated peak in
      cycling mice. The increase in CD4(+)CD25(+) cells was abrogated when males were
      vasectomized or seminal vesicles were excised. Collectively, these data provide
      evidence that exposure to seminal fluid at mating promotes a state of functional
      tolerance to paternal alloantigens that may facilitate maternal acceptance of the
      conceptus at implantation, and the effects of seminal fluid are likely to be
      mediated by expansion of the Treg cell pool. Both seminal plasma and sperm
      components of the seminal fluid are necessary to confer full tolerance and elicit
      the Treg cell response, potentially through provision of immune-deviating
      cytokines and antigens, respectively.

PMID- 19164171
TI  - Cell-free extracts from mammalian oocytes partially induce nuclear reprogramming
      in somatic cells.
AB  - Nuclear transfer has been regarded as the only reliable tool for studying nuclear
      reprogramming of mammalian somatic cells by oocytes. However, nuclear transfer is
      not well suited for biochemical analyses of the molecular mechanisms of
      reprogramming. A cell-free system from oocytes is an attractive alternative way
      to mimic reprogramming in vitro, since a large number of cells can be treated and
      analyzed. Nevertheless, a cell-free system using oocytes has not been developed
      in mammals. Here, cell extracts from porcine oocytes were prepared and their
      ability to induce nuclear reprogramming was evaluated. Extracts from metaphase II
      (MII) oocytes erased the machinery for regulating gene expression in reversibly
      permeabilized somatic cells. For example, the extracts caused histone
      deacetylation and the disappearance of TATA box-binding protein from the nuclei.
      However, MII-extract-treated cells did not show any obvious changes after cell
      culture. In contrast, extracts from germinal vesicle (GV) oocytes activated
      pluripotent marker genes, especially NANOG, and induced partial dedifferentiation
      after cell culture. The activation of pluripotent marker genes by GV extracts was
      associated with histone acetylation that was induced during extract treatment.
      These results indicate that GV- and MII-oocyte extracts have different roles on
      nuclear reprogramming. Furthermore, both oocyte extracts induced site-specific
      demethylation in the upstream region of NANOG. These results indicate that cell
      free extracts derived from GV- and MII-oocytes could be useful for studying the
      mechanisms involved in nuclear reprogramming.

PMID- 19164170
TI  - Variation in the ovarian reserve is linked to alterations in intrafollicular
      estradiol production and ovarian biomarkers of follicular differentiation and
      oocyte quality in cattle.
AB  - The mechanisms whereby the high variation in numbers of morphologically healthy
      oocytes and follicles in ovaries (ovarian reserve) may have an impact onovarian
      function, oocyte quality, and fertility are poorly understood. The objective was
      to determine whether previously validated biomarkers for follicular
      differentiation and function, as well as oocyte quality differed between cattle
      with low versus a high antral follicle count (AFC). Ovaries were removed (n = 5
      per group) near the beginning of the nonovulatory follicular wave, before
      follicles could be identified via ultrasonography as being dominant, from heifers
      with high versus a low AFC. The F1, F2, and F3 follicles were dissected and
      diameters determined. Follicular fluid and thecal, granulosal, and cumulus cells
      and the oocyte were isolated and subjected to biomarker analyses. Although the
      size and numerous biomarkers of differentiation, such as mRNAs for the
      gonadotropin receptors, were similar, intrafollicular concentrations of estradiol
      and the abundance of mRNAs for CYP19A1 in granulosal cells and ESR1, ESR2, and
      CTSB in cumulus cells were greater, whereas mRNAs for AMH in granulosal cells and
      TBC1D1 in thecal cells were lower for animals with low versus a high AFC during
      follicle waves. Hence, variation in the ovarian reserve may have an impact on
      follicular function and oocyte quality via alterations in intrafollicular
      estradiol production and expression of key genes involved in follicle-stimulating
      hormone action (AMH) and estradiol (CYP19A1) production by granulosal cells,
      function and survival of thecal cells (TBC1D1), responsiveness of cumulus cells
      to estradiol (ESR1, ESR2), and cumulus cell determinants of oocyte quality
      (CTSB).

PMID- 19164172
TI  - Female mice delay reproductive aging in males.
AB  - Reproductive aging of the male is characterized by decreasing fertility; however,
      factors that protect against reproductive aging in the male are largely unknown.
      Previous work has demonstrated that both female presence and aging have a
      dramatic effect on fertility in the male; yet, the effect of female presence on
      fertility in the aging male mouse is unknown. The objective of this work was to
      determine the effect of long-term isolation or cohabitation with females on
      fertility in aged male mice. Male mice were housed with or without females until
      between 16 and 32 mo of age. Males were subjected to fertility tests at specific
      ages, after which serum and testes were isolated for radioimmunoassay and
      histological analysis. We show that male mice continuously housed with females
      remain fertile longer ( approximately 20% of the reproductive lifespan) than male
      mice housed alone. Fertility became significantly reduced 6 mo sooner for males
      housed alone compared with males housed with females; however, the rate of
      decline was the same for males housed with or without females once fertility
      began to decrease. Testis weight decreased as the mice aged, and a nearly
      significant positive effect of female presence was observed. Additionally,
      histological analysis indicated that abnormal spermatogenesis occurred sooner in
      isolated males, suggesting that defects in spermatogenesis may play a role in the
      greater decrease in fertility in isolated males. These results have significant
      implications for the maintenance of male fertility in wildlife, livestock, and
      human populations.

PMID- 19164173
TI  - Compartmentalization of proteins in epididymosomes coordinates the association of
      epididymal proteins with the different functional structures of bovine
      spermatozoa.
AB  - Epididymosomes are small membranous vesicles secreted by epithelial cells within
      the luminal compartment of the epididymis. In bovine, many proteins are
      associated with epididymosomes, and some of them, such as the
      glycosylphosphatidylinositol (GPI)-anchored protein P25b, macrophage migration
      inhibitory factor (MIF), and aldose reductase (AKR1B1), are transferred to
      spermatozoa during the epididymal maturation process. P25b is associated with
      detergent-resistant membrane (DRM) domains of epididymal spermatozoa, whereas MIF
      and AKR1B1 are cytosolic proteins associated with detergent-soluble fractions. In
      this study, we tested the hypothesis that DRM domains are also present in the
      epididymosomes and that P25b DRM-associated proteins in these vesicles are
      transferred to the DRMs of spermatozoa. The presence of DRMs in epididymosomes
      was confirmed by their insolubility in cold Triton X-100 and their low buoyant
      density in sucrose gradient. Furthermore, DRMs isolated from epididymosomes are
      characterized by the exclusive presence of ganglioside GM1 and by high levels of
      cholesterol and sphingomyelin. Biochemical analysis indicated that P25b is linked
      to DRM in epididymosomes, whereas MIF and AKR1B1 are completely excluded from
      these membrane domains. Proteolytic treatment of epididymosomes and
      immunoblotting studies showed that P25b is affected by trypsin or pronase
      proteolysis. In contrast, MIF and AKR1B1 are not degraded by proteases,
      suggesting that they are localized within epididymosomes. Interaction studies
      between epididymosomes and epididymal spermatozoa demonstrated that P25b is
      transferred from the DRM of epididymosomes to the DRM of the caput epididymal
      spermatozoa as a GPI-anchored protein. Together, these data suggest that specific
      localization and compartmentalization of proteins in the epididymosomes
      coordinate the association of epididymal proteins with the different functional
      structures of spermatozoa.

PMID- 19164174
TI  - Interferon gamma in successful pregnancies.
AB  - Interferon gamma (IFNG) is a proinflammatory cytokine secreted in the uterus
      during early pregnancy. It is abundantly produced by uterine natural killer cells
      in maternal endometrium but also by trophoblasts in some species. In normal
      pregnancies of mice, IFNG plays critical roles that include initiation of
      endometrial vasculature remodeling, angiogenesis at implantation sites, and
      maintenance of the decidual (maternal) component of the placenta. In livestock
      and in humans, deviations in these processes are thought to contribute to serious
      gestational complications, such as fetal loss or preeclampsia. Interferon gamma
      has broader roles in activation of innate and adaptive immune responses to
      viruses and tumors, in part through upregulating transcription of genes involved
      in cell cycle regulation, apoptosis, and antigen processing/presentation. Despite
      this, rodent and human trophoblast cells show dampened responses to IFNG that
      reflect the resistance of these cells to IFNG-mediated activation of major
      histocompatibility complex (MHC) class II transplantation antigen expression.
      Lack of MHC class II antigens on trophoblasts is thought to facilitate survival
      of the semiallogeneic conceptus in the presence of maternal lymphocytes. This
      review describes the dynamic roles of IFNG in successful pregnancy and briefly
      summarizes data on IFNG in gestational pathologies.

PMID- 19164176
TI  - Proliferative activity in vitro and DNA repair indicate that adult mouse and
      human Sertoli cells are not terminally differentiated, quiescent cells.
AB  - Sertoli cells isolated from the adult mouse and human testis resume proliferation
      in culture. After 20 days of culture in Dulbecco modified Eagle medium/Ham F12
      (DMEM/F12) medium containing 5%% fetal calf serum, about 36%% of the mouse
      Sertoli cells, identified by their immunohistochemical staining for the Sertoli
      cell marker vimentin, incorporated bromodeoxyuridine (BrdU). The renewed
      proliferation was associated with a 70%% decrease in expression of the cell cycle
      inhibitor CDKN1B (P27(kip1)) and a 2-fold increase in the levels of the
      proliferation inducer ID2. In vivo, the balance between cell cycle inhibitors and
      inducers probably is such that the cells remain quiescent, whereas in culture the
      balance is disturbed such that Sertoli cells start to proliferate again. The
      renewed proliferative activity of Sertoli cells in culture was further confirmed
      by double staining for BrdU and the Sertoli cell marker clusterin (CLU), showing
      about 25%% of the CLU-positive Sertoli cells to be also positive for BrdU after
      13 days of culture. Radiobiologically, Sertoli cells are also different from
      other quiescent somatic cells in the testis because they express several DNA
      repair proteins (XRCC1, PARP1, and others). Indeed, a comet assay on irradiated
      Sertoli cells revealed a 70%% reduction in tail length and tail moment at 20 h
      after irradiation. Hence, Sertoli cells repair DNA damage, whereas other
      quiescent somatic testicular cells do not. This repair may be accomplished by
      nonhomologous end joining via XRCC1 and PARP1. In conclusion, cell kinetic and
      radiobiological data indicate that Sertoli cells more resemble arrested
      proliferating cells than the classic postmitotic and terminally differentiated
      somatic cells that they have always been assumed to be.

PMID- 19164175
TI  - Estrogen receptor immunoreactivity in late-gestation fetal lambs.
AB  - Prenatal androgens masculinize postnatal reproductive neuroendocrine function and
      behavior in sheep. Testosterone treatment of pregnant ewes during midgestation
      masculinizes sexual behavior and luteinizing hormone secretion in female lambs,
      presumably in part via aromatization and estrogen receptor (ESR) binding in the
      brain. We hypothesized that male and female sheep also differ in the number and
      distribution of ESR-containing neurons. If so, ESR expression should be sensitive
      to prenatal hormones delivered exogenously or in situ. ESR alpha (ESR1) was
      compared by immunocytochemistry in male and female lambs at the end of gestation,
      as well as in fetal females exposed prenatally to testosterone or
      dihydrotestosterone. ESR1-positive neurons were abundant in the posteromedial bed
      nucleus of the stria terminalis (BSTpm), medial preoptic area (MPOA), posterior
      medial amygdaloid nucleus (MeP), amygdalohippocampal area (AHi), ventromedial
      hypothalamic nuclei (VMH), and arcuate hypothalamic nuclei (ARC). In females, the
      ARC had the largest number of stained cells (mean +/- SEM, 475.6 +/- 57.4
      cells/0.173 mm(2)), while staining intensity was greatest in the MPOA (mean +/-
      SEM gray level, 31.3 +/- 5.3). The mean +/- SEM integrated gray level (IGL) was
      high in the ARC (0.63 +/- 0.13) and in the MPOA (0.51 +/- 0.08). The mean +/- SEM
      IGL was low in the MeP (0.31 +/- 0.10) and in the BSTpm (0.21 +/- 0.06), while it
      was intermediate in the AHi (0.36 +/- 0.10) and in the VMH (0.37 +/- 0.07). ESR
      immunostaining was not significantly different in male and female fetal lambs,
      nor in females fetuses exposed prenatally to androgens (P > 0.05). However, ESR1
      staining was significantly increased in the ARC, MPOA, and AHi of adult rams vs.
      adult ewes. These results suggest that brain ESR immunoreactivity in fetal lambs
      is unlikely to account for postnatal sex differences in reproductive function.
      Instead, sex differences in ESR emerge postnatally.

PMID- 19164177
TI  - Use of sperm plasmid DNA lipofection combined with REMI (restriction enzyme
      mediated insertion) for production of transgenic chickens expressing eGFP
      (enhanced green fluorescent protein) or human follicle-stimulating hormone.
AB  - Linearized p-eGFP (plasmid-enhanced green fluorescent protein) or p-hFSH (plasmid
      human FSH) sequences with the corresponding restriction enzyme were lipofected
      into sperm genomic DNA. Sperm transfected with p-eGFP were used for artificial
      insemination in hens, and in 17 out of 19 of the resultant chicks, the exogenous
      DNA was detected in their lymphocytes as determined by PCR and expressed in
      tissues as determined by (a) PCR, (b) specific emission of green fluorescence by
      the eGFP, and (c) Southern blot analysis. A complete homology was found between
      the Aequorea Victoria eGFP DNA and a 313-bp PCR product of extracted DNA from
      chick blood cells. Following insemination with sperm lipofected with p-hFSH,
      transgenic offspring were obtained for two generations as determined by detection
      of the transgene for human FSH (PCR) and expression of the gene (RT-PCR and
      quantitative real-time PCR) and the presence of the protein in blood
      (radioimmunoassay). Data demonstrate that lipofection of plasmid DNA with
      restriction enzyme is a highly efficient method for the production of transfected
      sperm to produce transgenic offspring by direct artificial insemination.

PMID- 19164178
TI  - Epithelial human chorionic gonadotropin is expressed and produced in human
      secretory endometrium during the normal menstrual cycle.
AB  - The objective of this study was to determine whether beta human chorionic
      gonadotropin (hCG) (CGB) subunits and alpha hCG (CGA) subunits are expressed and
      the hCG dimer is produced in normal human cyclic endometrium. Endometrial
      specimens were collected for histological dating from women undergoing treatment
      in our division of human reproduction. RNA from normal secretory endometrium was
      extracted, and CGB and CGA gene expression was assessed by semiquantitative PCR.
      Adequate secretory endometrial specimens were homogenized using protease
      inhibitors. Proteins present in the supernatant were separated
      electrophoretically, and molecular hCG isoforms were detected by Western blot.
      The supernatant hCG concentrations were measured by ELISA. We characterized hCG
      and leukocytes in endometrial specimens by immunohistochemistry. Uterine flushing
      was performed to confirm endometrial hCG secretion into the uterine fluid. A full
      length CGB mRNA encompassing the exon 1 promoter region and the structure exons 2
      and 3 (including the C-terminal peptide) was expressed in normal secretory
      endometrial specimens (similar to CGA) during the early secretory phase of the
      menstrual cycle, up to an optimum at the midsecretory to late secretory phases.
      In homogenate supernatants obtained from normal secretory endometrium, hormone
      concentrations of dimeric hCG were approximately 5 mU per 10 mg of tissue,
      compared with considerably smaller concentrations of corresponding single free
      CGB subunit. Single chains of CGB, CGA, and dimeric molecular hCG isoforms were
      found in endometrial specimens by Western blot. Glandular endometrial hCG
      production is demonstrated immunohistochemically, with an increase toward the
      late secretory phase vs. the early secretory phase of the normal secretory
      menstrual cycle. However, glandular hCG release is diminished or absent in the
      dyssynchronous or missing endometrial secretory transformation. Endogenous
      endometrial hCG may be important for implantation and maintenance of pregnancy.

PMID- 19164179
TI  - Differential gene expression in the bovine corpus luteum during transition from
      early phase to midphase and its potential role in acquisition of luteolytic
      sensitivity to prostaglandin F2 alpha.
AB  - Prostaglandin F2 alpha (PGF(2alpha)) brings about regression of the bovine corpus
      luteum (CL). This luteolytic property of PGF(2alpha) is used in beef and dairy
      cattle to synchronize estrus. A limitation of this protocol is insensitivity of
      the early CL to luteolytic actions of PGF(2alpha). The mechanisms underlying this
      differential luteal sensitivity are poorly understood. The developing CL has a
      maximum number of PGF(2alpha) receptors; therefore, differences in signaling
      events may be responsible for luteal insensitivity. Hence, differential gene
      expression at two developmental stages of CL, Day 4 (D-4) and D-10 after estrus,
      might account for differences in signal transduction pathways associated with
      luteal sensitivity. This possibility was examined in these studies. Microarray
      analysis (n = 3 cows per stage) identified 167 genes that were differentially
      expressed (P < 0.05). These were categorized into genes involved in protein
      biosynthesis and modification (18.5%), transcription regulation and DNA
      biosynthesis (18.5%), miscellaneous (17.0%), cell signaling (12.0%),
      steroidogenesis and metabolism (10.2%), extracellular matrix and cytoskeletal
      proteins (9.5%), unknown functions (6.0%), protein degradation (5.3%), and
      antioxidant property (3.0%). Real-time PCR confirmed the differential expression
      of nine selected genes, including tyrosine 3-monooxygenase/tryptophan 5
      monooxygense activation protein zeta polypeptide (YWHAZ) and regulator of G
      protein signaling 2 24-kDa (RGS2), observed in microarray. Furthermore, the in
      vivo effect of exogenous PGF(2alpha) (n = 3 cows per stage) on selected genes
      that were found to be differentially expressed during this developmental
      transition was examined. PGF(2alpha) increased the expression of a guanine
      nucleotide-binding protein (G protein) beta polypeptide 1 (GNB1) in D-4 CL and
      calcium/calmodulin-dependent kinase kinase 2 beta (CAMKK2) in D-10 CL. Therefore,
      GNB1, CAMKK2, YWHAZ, and RGS2 are candidate genes that may have a significant
      role in acquisition of luteal sensitivity to PGF(2alpha). Additional evidence
      supporting the significance of the microarray data was obtained from the
      observation that the amount of CAMKK2 paralleled the differential mRNA expression
      observed for this gene when examined by microarray analysis and by real-time RT
      PCR. Furthermore, the two types of luteal steroidogenic cells known to be targets
      for PGF(2alpha) actions were demonstrated to be a cellular source for CAMKK2.

PMID- 19164180
TI  - Differences in collagen expression in cumulus cells after exposure to highly
      purified menotropin or recombinant follicle-stimulating hormone in a mouse
      follicle culture model.
AB  - Extracellular matrix (ECM) formation by cumulus cells is an important process
      that determines fertilization and embryo quality. Several collagen types are
      present in the ovarian follicular ECM and are related to proliferation,
      steroidogenesis, and luteinization. In vitro mouse follicles can optimally grow
      and provide developmentally competent oocytes with 10 IU/L recombinant follicle
      stimulating hormone (rFSH). As a model for superovulation, experiments with 100
      IU/L rFSH or 100 IU/L highly purified menotropin (HP-hMG) exposure during antral
      growth were undertaken. Col4a1, Col4a2, and Col6a2 expression levels were
      analyzed at three time points during antral growth and at a 4-h interval up to 16
      h after ovulation induction using quantitative PCR. The presence and induction of
      the collagen mRNA and protein were confirmed in cumulus from in vivo- and in
      vitro-grown follicles, and TGFBs 1 and 2 were assayed as potential regulators.
      The study revealed that exposure to 100 IU/L FSH, as in both superovulation
      conditions, significantly influenced the follicle morphology and slowed down
      nuclear maturation and mucification (P < 0.05). This coincided with an increased
      expression of the three collagens in the cumulus-oocyte complex at the end of
      antral growth and in the first hours following the ovulatory dose of human
      chorionic gonadotropin (P < 0.05). The increased expression might reflect a
      differentiation but is most likely due to a precocious luteinization of the
      cumulus. Growth in HP-hMG resulted in higher Tgfb1 mRNA and protein levels, fewer
      COCs with an increased collagen expression and with a more synchronous nuclear
      maturation. This suggests that the presence of luteinizing hormone activity
      tempered the effect of the elevated FSH dose.

PMID- 19164182
TI  - Health care and the recession.

PMID- 19164183
TI  - Great expectations--the Obama administration and health care reform.

PMID- 19164181
TI  - Extra-germ cell expression of mouse nuclear receptor subfamily 6, group A, member
      1 (NR6A1).
AB  - Nuclear receptor subfamily 6, group A, member 1 (NR6A1) is an orphan member of
      the nuclear receptor superfamily and is required for normal mouse embryonic
      development. In adult mice, NR6A1 is predominantly expressed in spermatogenic
      cells and growing oocytes of the gonads and has a role in female reproduction by
      modulating the transcription of the oocyte-specific genes bone morphogenetic
      protein 15 (Bmp15) and growth differentiation factor 9 (Gdf9). In our goal to
      further understand the functional role of NR6A1 during postnatal development, we
      generated a Nr6a1:beta-galactosidase (LacZ) knockin reporter (Nr6a1(LacZ/+))
      mouse line in which the Nr6a1:LacZ fusion gene was expressed and then
      characterized Nr6a1 expression in these reporter mice by performing LacZ
      staining. Our RT-PCR analyses showed that Nr6a1 was expressed in a variety of
      somatic tissues (e.g., oviduct and lung) other than gonads of normal adult mice.
      In adult Nr6a1(LacZ/+) mice, robust LacZ staining was observed in the gametes of
      gonads. Strong positive LacZ staining was also observed in the sperm of the
      epididymis, epithelial cells of the oviduct, and bronchioles within the lung. In
      adult Nr6a1(LacZ/+) mice, positive LacZ staining was observed in other somatic
      tissues, including hippocampus, cerebral cortex, cerebellum, and thalamus of
      brain; pars intermedia and pars anterior of pituitary; parathyroid; and islet of
      pancreas. NR6A1 expression in sperm within the epididymis, epithelial cells in
      the oviduct, and bronchioles of the lung was further confirmed by
      immunohistochemical studies. Nr6a1 is expressed not only in the germ cells of
      mouse gonads but also in a variety of somatic tissues, including epididymis,
      oviduct, brain, and pituitary. The extra-germ cell expression of NR6A1 makes it a
      less attractive contraceptive.

PMID- 19164184
TI  - Medicaid and the U.S. path to national health insurance.

PMID- 19164185
TI  - Online disclosure of physician-industry relationships.

PMID- 19164186
TI  - Oral prednisolone for preschool children with acute virus-induced wheezing.
AB  - BACKGROUND: Attacks of wheezing induced by upper respiratory viral infections are
      common in preschool children between the ages of 10 months and 6 years. A short
      course of oral prednisolone is widely used to treat preschool children with
      wheezing who present to a hospital, but there is conflicting evidence regarding
      its efficacy in this age group. METHODS: We conducted a randomized, double-blind,
      placebo-controlled trial comparing a 5-day course of oral prednisolone (10 mg
      once a day for children 10 to 24 months of age and 20 mg once a day for older
      children) with placebo in 700 children between the ages of 10 months and 60
      months. The children presented to three hospitals in England with an attack of
      wheezing associated with a viral infection; 687 children were included in the
      intention-to-treat analysis (343 in the prednisolone group and 344 in the placebo
      group). The primary outcome was the duration of hospitalization. Secondary
      outcomes were the score on the Preschool Respiratory Assessment Measure,
      albuterol use, and a 7-day symptom score. RESULTS: There was no significant
      difference in the duration of hospitalization between the placebo group and the
      prednisolone group (13.9 hours vs. 11.0 hours; ratio of geometric means, 0.90;
      95% confidence interval, 0.77 to 1.05) or in the interval between hospital
      admission and signoff for discharge by a physician. In addition, there was no
      significant difference between the two study groups for any of the secondary
      outcomes or for the number of adverse events. CONCLUSIONS: In preschool children
      presenting to a hospital with mild-to-moderate wheezing associated with a viral
      infection, oral prednisolone was not superior to placebo. (Current Controlled
      Trials number, ISRCTN58363576.)

PMID- 19164187
TI  - Preemptive use of high-dose fluticasone for virus-induced wheezing in young
      children.
AB  - BACKGROUND: Although virus-induced wheezing is common in preschool-age children,
      optimal management remains elusive. We examined the efficacy and safety of
      preemptive treatment with high-dose fluticasone in reducing the severity of
      recurrent virus-induced wheezing in children. METHODS: We randomly assigned 129
      children who were 1 to 6 years of age to receive 750 microg of fluticasone
      propionate (ex-valve [manufacturer-measured] dose) or placebo twice daily,
      beginning at the onset of an upper respiratory tract infection and continuing for
      a maximum of 10 days, over a period of 6 to 12 months. The primary outcome was
      rescue oral corticosteroid use. Secondary outcomes included symptoms, use of
      beta(2)-agonists, acute care visits, hospitalizations, discontinuation of the
      study drug, change in growth and bone mineral density, basal cortisol level, and
      adverse events. RESULTS: Over a median period of 40 weeks, 8% of upper
      respiratory tract infections in the fluticasone group led to treatment with
      rescue systemic corticosteroids, as compared with 18% in the placebo group (odds
      ratio, 0.49; 95% confidence interval [CI], 0.30 to 0.83). Children who were
      treated with fluticasone, as compared with those who were given placebo, had
      smaller mean (+/-SD) gains from baseline in height (6.23+/-2.62 cm [unadjusted
      value]; z score, -0.19 +/-0.42 vs. 6.56+/-2.90 cm [unadjusted value]; z score,
      0.00+/-0.48; difference between groups in z score from baseline to end point, 
      0.24 [95% CI, -0.40 to -0.08]) and in weight (1.53+/-1.17 kg [unadjusted value];
      z score, -0.15+/-0.48 vs. 2.17+/-1.79 kg [unadjusted value]; z score, 0.11+/
      0.43; difference between groups in z score from baseline to end point, -0.26 [95%
      CI, -0.41 to -0.09]). There were no significant differences between the groups in
      basal cortisol level, bone mineral density, or adverse events. CONCLUSIONS: In
      preschool-age children with moderate-to-severe virus-induced wheezing, preemptive
      treatment with high-dose fluticasone as compared with placebo reduced the use of
      rescue oral corticosteroids. Treatment with fluticasone was associated with a
      smaller gain in height and weight. Given the potential for overuse, this
      preventive approach should not be adopted in clinical practice until long-term
      adverse effects are clarified. (ClinicalTrials.gov number, NCT00238927.)

PMID- 19164188
TI  - Fine-particulate air pollution and life expectancy in the United States.
AB  - BACKGROUND: Exposure to fine-particulate air pollution has been associated with
      increased morbidity and mortality, suggesting that sustained reductions in
      pollution exposure should result in improved life expectancy. This study directly
      evaluated the changes in life expectancy associated with differential changes in
      fine particulate air pollution that occurred in the United States during the
      1980s and 1990s. METHODS: We compiled data on life expectancy, socioeconomic
      status, and demographic characteristics for 211 county units in the 51 U.S.
      metropolitan areas with matching data on fine-particulate air pollution for the
      late 1970s and early 1980s and the late 1990s and early 2000s. Regression models
      were used to estimate the association between reductions in pollution and changes
      in life expectancy, with adjustment for changes in socioeconomic and demographic
      variables and in proxy indicators for the prevalence of cigarette smoking.
      RESULTS: A decrease of 10 microg per cubic meter in the concentration of fine
      particulate matter was associated with an estimated increase in mean (+/-SE) life
      expectancy of 0.61+/-0.20 year (P=0.004). The estimated effect of reduced
      exposure to pollution on life expectancy was not highly sensitive to adjustment
      for changes in socioeconomic, demographic, or proxy variables for the prevalence
      of smoking or to the restriction of observations to relatively large counties.
      Reductions in air pollution accounted for as much as 15% of the overall increase
      in life expectancy in the study areas. CONCLUSIONS: A reduction in exposure to
      ambient fine-particulate air pollution contributed to significant and measurable
      improvements in life expectancy in the United States.

PMID- 19164189
TI  - Clinical practice. Seborrheic dermatitis.

PMID- 19164190
TI  - Images in clinical medicine. A medical mystery--constipation.

PMID- 19164191
TI  - Case records of the Massachusetts General Hospital. Case 3-2009. A 9-month-old
      boy with seizures.

PMID- 19164192
TI  - Practice imperfect--treatment for wheezing in preschoolers.

PMID- 19164193
TI  - Clopidogrel, genetics, and drug responsiveness.

PMID- 19164194
TI  - Evaluating the effects of ambient air pollution on life expectancy.

PMID- 19164195
TI  - Follow-up of intensive glucose control in type 2 diabetes.

PMID- 19164196
TI  - Breast reconstruction after breast-cancer surgery.

PMID- 19164197
TI  - Executive physicals.

PMID- 19164198
TI  - Treatment of growing teratoma syndrome.

PMID- 19164199
TI  - Excess iodine from an unexpected source.

PMID- 19164200
TI  - Why does levator ani nerve damage occur during rectal surgery?

PMID- 19164201
TI  - Different natural course of disease in patients with melanoma.

PMID- 19164202
TI  - Sharing study results with trial participants: time for action.

PMID- 19164203
TI  - Phase II study of capecitabine and oxaliplatin for advanced adenocarcinoma of the
      small bowel and ampulla of Vater.
AB  - PURPOSE: Adenocarcinomas of the small bowel and ampulla of Vater represent rare
      cancers that have limited data regarding first-line therapy. We conducted a phase
      II trial to evaluate the benefit of capecitabine in combination with oxaliplatin
      (CAPOX) in patients with advanced adenocarcinoma of small bowel or ampullary
      origin. PATIENTS AND METHODS: Eligible patients with metastatic or unresectable
      tumors and no prior systemic chemotherapy for advanced disease participated in
      this phase II trial. CAPOX was administered as a 21-day cycle with oxaliplatin
      130 mg/m(2) on day 1 and capecitabine 750 mg/m(2) twice a day on days 1 through
      14. The primary end point was overall response rate as assessed by Response
      Evaluation Criteria in Solid Tumors. RESULTS: Thirty-one patients were enrolled
      onto the study, and 30 patients received study treatment. The confirmed overall
      response rate was 50%; three patients with metastatic disease achieved complete
      responses. The median time to progression (TTP) was 11.3 months, and the median
      overall survival (OS) was 20.4 months. Subset analysis of patients with
      metastatic disease only (n = 25) revealed a median TTP of 9.4 months and median
      OS of 15.5 months. The most common grades 3 or 4 toxicities included fatigue
      (30%), peripheral neuropathy (10%), vomiting (10%), diarrhea (10%), and
      neutropenia (10%). CONCLUSION: When administered to patients with good
      performance status, CAPOX is well tolerated and produces a superior response rate
      and longer OS compared with other regimens in the literature. CAPOX should be
      considered a new standard regimen for advanced small bowel and ampullary
      adenocarcinomas.

PMID- 19164204
TI  - Immunoglobulin M amyloidosis.

PMID- 19164205
TI  - Overcoming CYP1A1/1A2 mediated induction of metabolism by escalating erlotinib
      dose in current smokers.
AB  - PURPOSE: Cigarette smoking induces CYP1A1/1A2 and is hypothesized to alter
      erlotinib pharmacokinetics. This study aimed to determine the maximum tolerated
      dose (MTD) of erlotinib in advanced non-small-cell lung cancer (NSCLC) patients
      who smoke and compare the pharmacokinetics of erlotinib at the MTD in current
      smokers with 150 mg. PATIENTS AND METHODS: Cohorts of NSCLC patients currently
      smoking > or = 10 cigarettes per day for > or = 1 year received escalating doses
      of erlotinib for 14 days until dose-limiting toxicity (DLT). A separate cohort of
      patients was then randomly assigned to erlotinib at either MTD or 150 mg daily
      with pharmacokinetics assessed at day 14. Erlotinib was continued until
      progression or intolerable toxicity. RESULTS: Four dose levels were evaluated in
      22 patients: 200, 250, 300, and 350 mg. DLT was observed in one of six patients
      at 300 mg (rash) and two of five patients at 350 mg (acneiform dermatitis and
      fatigue/decreased Eastern Cooperative Oncology Group performance status). Thirty
      five patients were randomly assigned to 150 mg or 300 mg. Common adverse events
      (all grades) were: skin toxicity (150 mg, 29%; 300 mg, 67%), diarrhea (150 mg,
      18%; 300 mg, 50%), and fatigue (150 mg, 12%; 300 mg, 17%). Erlotinib exposure was
      dose-proportional within dose range tested. Median steady-state trough erlotinib
      plasma concentrations were 0.375 and 1.22 microg/mL for 150 mg and 300 mg,
      respectively. CONCLUSION: The MTD of erlotinib in NSCLC patients who smoke was
      300 mg. Steady-state trough plasma concentrations and incidence of rash and
      diarrhea in smokers at 300 mg were similar to those in former or never smokers
      receiving 150 mg in previous studies. The potential benefit of higher erlotinib
      doses in current smokers warrants further evaluation.

PMID- 19164206
TI  - Epigenetic regulation of microRNAs in acute lymphoblastic leukemia.
AB  - PURPOSE: To identify microRNAs (miRNAs) epigenetically regulated in acute
      lymphoblastic leukemia (ALL). METHODS: We first examined ALL-derived cell lines
      for the presence of abnormal levels of two different histone modifications
      (trimethylation of H3 lysine 4 [K4H3me3] and dimethylation of H3 lysine 9
      [K9H3me2]) in the 5'UTR regions around CpG islands of 78 miRNAs by chromatin
      immunoprecipitation (ChIP)-on-ChIP analysis. Methylation status (methylation
      specific polymerase chain reaction [PCR]) and expression (quantitative PCR) of
      miRNAs showing a pattern of histone modifications linked to a closed chromatin
      structure were analyzed in a panel of six ALL cell lines and in 353 ALL patients.
      RESULTS: CpG islands around 13 miRNAs disclosed high levels of K9H3me2 and/or low
      levels of K4H3me3, a pattern of histone modifications underlying a closed
      chromatin structure associated with repressive gene expression. Complete
      consistency in the correlation between both histone marks, the presence of DNA
      methylation around these miRNAs, and their expression patterns was confirmed in
      the six ALL cell lines. Treatment with 5-Aza-2'-deoxycytidine upregulated the
      expression levels of these genes, suggesting that epigenetic mechanisms
      deregulate the expression of these miRNAs. A total of 65% of the ALL samples had
      at least one miRNA methylated (methylated group). Estimated disease-free survival
      (DFS) and overall survival (OS) at 14 years were 78% and 71% for nonmethylated
      patients and 24% and 28% for methylated patients (P = .00001 for both).
      Multivariate analysis demonstrated that methylation profile was an independent
      prognostic factor for predicting DFS (P = .0001) and OS (P = .0001). CONCLUSION:
      Aberrant miRNA methylation is a common phenomenon in ALL that affects the
      clinical outcome of these patients.

PMID- 19164207
TI  - Acute abnormalities of sensory nerve function associated with oxaliplatin-induced
      neurotoxicity.
AB  - PURPOSE: Neurotoxicity is becoming increasingly recognized as the major dose
      limiting toxicity of oxaliplatin. Because the mechanism of oxaliplatin-induced
      neurotoxicity remains unclear, the present study investigated the potential of
      axonal excitability techniques in identifying pathophysiologic mechanisms and
      early markers of nerve dysfunction. PATIENTS AND METHODS: Measures of sensory
      axonal excitability were recorded before and after infusion over 88 treatment
      cycles in 25 patients with colorectal cancer, who received a total oxaliplatin
      dose of 766 +/- 56 mg/m(2). Neurologic assessment, clinical rating scales, and
      routine nerve conduction studies were performed. RESULTS: By completion of
      treatment, 16% of patients had developed severe (grade 3) neurotoxicity, and
      oxaliplatin dose reduction or cessation as a result of neurotoxicity was required
      in 40% of patients. Changes in axonal excitability occurred after infusion and
      could be explained on the basis of alterations in axonal membrane sodium (Na+)
      channel function (refractoriness: 7.6% +/- 1.7% before infusion v 4.5% +/- 1.4%
      after infusion; P = .03; superexcitability: -22.8% +/- 0.8% before infusion v 
      20.1% +/- 1.1% after infusion; P = .0002). Changes became less pronounced in
      later treatment cycles, suggesting that chronic nerve dysfunction and sensory
      loss masked acute effects at higher cumulative doses. Importantly, patients who
      demonstrated reductions in superexcitability in early treatment were subsequently
      more likely to develop moderate to severe neurotoxicity. The findings suggest
      that the degree of acute nerve dysfunction may relate to the development of
      chronic neurotoxicity. CONCLUSION: Sensory axonal excitability techniques may
      facilitate identification of Na+ channel dysfunction in oxaliplatin-induced
      neurotoxicity and thereby provide a method to identify patients at risk for
      neurotoxicity to target those most likely to benefit from future neuroprotective
      strategies.

PMID- 19164208
TI  - Evaluation of screening instruments for cancer-related fatigue syndrome in breast
      cancer survivors.
AB  - PURPOSE: Cases of cancer-related fatigue syndrome (CRFS) can be reliably
      indentified using a diagnostic interview combined with a structured psychiatric
      interview. However, these interviews are time consuming to conduct, require
      specialist training, and are not suitable for routine clinical use. The purpose
      of this study was to identify whether a screening questionnaire could identify
      patients at high risk of clinically significant fatigue who should be considered
      for a suitable intervention. PATIENTS AND METHODS: The diagnostic interview for
      CRFS and the structured clinical interview for the diagnostic and statistical
      manual of mental disorders were used in order to identify breast cancer survivors
      who fulfilled the criteria for CRFS. Two fatigue questionnaires (the
      Bidimensional Fatigue Scale [BFS] and the Functional Assessment of Cancer Therapy
      Fatigue subscale [FACT-F]) were administered in order to determine their
      screening properties. RESULTS: Two hundred women were interviewed and 60 women
      fulfilled the criteria for CRFS. The BFS cutoff score of 11 had a sensitivity of
      92%, a specificity of 53%, a positive predictive value (PPV) of 46%, and a
      negative predictive value (NPV) of 94%. The FACT-F cutoff score of 36 had a
      sensitivity of 80%, a specificity of 71%, a PPV of 55%, and a NPV of 89%.
      CONCLUSION: The BFS and FACT-F cutoff scores can be used to identify breast
      cancer survivors at higher risk of clinically significant ongoing post treatment
      fatigue. Neither scale can be used as a diagnostic instrument for CRFS.

PMID- 19164209
TI  - Postmastectomy radiotherapy: will the selective use of postmastectomy
      radiotherapy study end the debate?

PMID- 19164210
TI  - Lymph node ratio as an alternative to pN staging in node-positive breast cancer.
AB  - PURPOSE: In the current pTNM classification system, nodal status of breast cancer
      is based on the number of involved lymph nodes and does not account for the total
      number of lymph nodes removed. In this study, we assessed the prognostic value of
      the lymph node ratio (LNR; ie, ratio of positive over excised lymph nodes) as
      compared with pN staging and determined its optimal cutoff points. PATIENTS AND
      METHODS: From the Geneva Cancer Registry, we identified all women diagnosed with
      node-positive breast cancer between 1980 and 2004 (n = 1,829). The prognostic
      value of LNRs was calculated for values ranging from 0.05 to 0.95 by Cox
      regression analysis and validated by bootstrapping. Based on maximum likelihood,
      we identified cutoff points classifying women into low-, intermediate-, and high
      risk LNR groups. RESULTS: Optimal cutoff points classified patients into low- (<
      or = 0.20), intermediate- (> 0.20 and < or = 0.65), and high-risk (> 0.65) LNR
      groups, corresponding to 10-year disease-specific survival rates of 75%, 63%, and
      40%, and adjusted mortality risks of 1 (reference), 1.78 (95% CI, 1.46 to 2.18),
      and 3.21 (95% CI, 2.54 to 4.06), respectively. In contrast to LNR risk
      categories, survival curves of pN2 and pN3 crossed after 15 years, and their
      adjusted mortality risks showed overlapping CIs: 2.07 (95% CI, 1.69 to 2.53) and
      2.84 (95% CI, 2.23 to 3.61), respectively. CONCLUSION: LNR predicts survival
      after breast cancer more accurately than pN classification and should be
      considered as an alternative to pN staging.

PMID- 19164211
TI  - Providing research results to participants: attitudes and needs of adolescents
      and parents of children with cancer.
AB  - PURPOSE: There is an increasing demand for researchers to provide research
      results to participants. Our aim was to define an appropriate process for this,
      based on needs and attitudes of participants. METHODS: A multicenter survey in
      five sites in the United States and Canada was offered to parents of children
      with cancer and adolescents with cancer. Respondents indicated their preferred
      mode of communication of research results with respect to implications; timing,
      provider, and content of the results; reasons for and against providing results;
      and barriers to providing results. RESULTS: Four hundred nine parents (including
      19 of deceased children) and 86 adolescents responded. Most parents (n = 385;
      94.2%) felt that they had a strong right to research results. For positive
      results, most wanted a letter or e-mail summary (n = 238; 58.2%) or a phone call
      followed by a letter (n = 100; 24.4%). If the results were negative, phone call
      (n = 136; 33.3%) or personal visits (n = 150; 36.7%) were preferred. Parents
      wanted the summary to include long-term sequelae and suggestions for participants
      (n = 341; 83.4%), effect on future treatments (n = 341; 83.4%), and subsequent
      research steps (n = 284; 69.5%). Understanding the researcher was a main concern
      about receiving results (n = 145; 35.5%). Parents felt that results provide
      information to support quality of life (n = 315; 77%) and raise public awareness
      of research (n = 282; 68.9%). Adolescents identified similar preferences.
      CONCLUSION: Parents of children with cancer and adolescents with cancer feel
      strongly that they have a right to be offered research results and have specific
      preferences of how and what information should be communicated.

PMID- 19164212
TI  - Prevention, screening, and surveillance care for breast cancer survivors compared
      with controls: changes from 1998 to 2002.
AB  - PURPOSE: To examine how care for breast cancer survivors compares with controls.
      PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results
      Medicare database, we examined five cohorts of stages 1 to 3 breast cancer
      survivors diagnosed from 1998 to 2002. For each survivor cohort (defined by
      diagnosis year), we calculated the number of visits to oncology specialists,
      primary care providers (PCPs), and other physicians and the percentage who
      received influenza vaccination, cholesterol screening, colorectal cancer
      screening, bone densitometry, and mammography during survivorship year 1 (days
      366 to 730 postdiagnosis). We compared survivors' care to that of five cohorts of
      screening controls who were matched to survivors on age, ethnicity, sex, and
      region and who had a mammogram in the survivor's year of diagnosis and to that of
      five cohorts of comorbidity controls who were matched on age, ethnicity, sex,
      region, and comorbidity. We examined whether survivors' care was associated with
      the mix of physician specialties that were visited. RESULTS: A total of 23,731
      survivors were matched with 23,731 screening controls and 23,396 comorbidity
      controls. There was no difference in trends over time in PCP visits between
      survivors and either control group. The survivors' rate of increase in other
      physician visits was greater than screening controls (P = .002) but was no
      different from comorbidity controls. Survivors were less likely to receive
      preventive care than screening controls but were more likely than comorbidity
      controls. Trends over time in survivors' care tended to be better than screening
      controls but were no different than comorbidity controls. Survivors who visited
      both a PCP and oncology specialist were most likely to receive recommended care.
      CONCLUSION: Involvement by both PCPs and oncology specialists can facilitate
      appropriate care for survivors.

PMID- 19164213
TI  - Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the
      clinical outcome of patients with metastatic colorectal cancer treated with
      cetuximab plus irinotecan.
AB  - PURPOSE: The antiepidermal growth factor receptor antibody cetuximab shows
      activity in irinotecan-refractory metastatic colorectal cancer (mCRC), mainly in
      wild-type KRAS tumors. Cetuximab may also exert antitumor effects through
      antibody-dependent cell-mediated cytotoxicity (ADCC) in which antibody Fc portion
      interacts with Fc receptors (FcgammaRs) expressed by immune cells. ADCC is
      influenced by FcgammaRIIa-H131R and FcgammaRIIIa-V158F polymorphisms that are
      clinically relevant in follicular lymphoma and metastatic breast cancer treated
      with rituximab and trastuzumab, respectively. We investigated the association of
      FcgammaR polymorphisms and KRAS mutation with the outcome of irinotecan
      refractory mCRC patients treated with cetuximab plus irinotecan. PATIENTS AND
      METHODS: Tumor and normal tissues from 69 patients were screened for KRAS
      mutations using a sensitive multiplex assay and genotyped for FcgammaRIIa and
      FcgammaRIIIa polymorphisms by direct sequencing and multiplex allele-specific
      polymerase chain reaction, respectively. The results were correlated with
      response and progression-free survival (PFS). RESULTS: KRAS mutations were
      associated with lower response rate (4% v 27% in nonmutated patients; P = .021)
      and shorter PFS (3.0 v 5.3 months; P = .021). Patients with FcgammaRIIa-131H/H
      and/or FcgammaIIIa-158V/V genotypes had longer PFS than 131R and 158F carriers
      (5.5 v 3.0 months; P = .005). The difference remained significant for mutated
      KRAS patients. By multivariate analysis, KRAS mutation and FcgammaR combined
      status were independent risk factors for PFS. CONCLUSION: Combined
      FcgammaRIIa/FcgammaRIIIa polymorphisms are prognostic factors for disease
      progression in mCRC patients treated with cetuximab plus irinotecan. As these
      polymorphisms are also clinically relevant in mutated-KRAS mCRC, an important
      role of ADCC in cetuximab efficacy is presumed.

PMID- 19164214
TI  - Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical
      outcomes in esophageal cancer patients treated with chemoradiotherapy.
AB  - PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog
      (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target
      of rapamycin (mTOR) signaling pathway has been implicated in resistance to
      several chemotherapeutic agents. In this retrospective study, we determined
      whether common genetic variations in this pathway are associated with clinical
      outcomes in esophageal cancer patients with adenocarcinoma or squamous cell
      carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS:
      Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1,
      AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for
      associations with response to therapy, survival, and recurrence. RESULTS: We
      observed an increased recurrence risk with genetic variations in AKT1 and AKT2
      (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to
      6.66, respectively). This effect was magnified with an increasing number of AKT
      adverse genotypes. In contrast, a predictable protective effect by PTEN genetic
      variants on recurrence was evident. Survival tree analysis identified higher
      order interactions that resulted in variation in recurrence-free survival from 12
      to 42 months, depending on the combination of SNPs. Genetic variations in AKT1,
      AKT2, and FRAP1 were associated with survival. Patients homozygous for either of
      the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two
      genes--AKT2 and FRAP1--were associated with a poor treatment response, while a
      better response was associated with heterozygosity for AKT1:rs3803304 (odds
      ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common
      genetic variations in this pathway modulate clinical outcomes in patients who
      undergo chemoradiotherapy. With further validation, these results may be used to
      build a model of individualized therapy for the selection of the optimal
      chemotherapeutic regimen.

PMID- 19164215
TI  - Cisplatin and etoposide in childhood germ cell tumor: brazilian pediatric
      oncology society protocol GCT-91.
AB  - PURPOSE: In 1988, we formed a consortium of Brazilian institutions to develop
      uniform standards for the diagnostic assessment and multidisciplinary treatment
      of children and adolescents with germ cell tumors. We also implemented the first
      childhood Brazilian germ cell tumor protocol, GCT-91, evaluating two-agent
      chemotherapy with cisplatin and etoposide (PE). We now report on the clinical
      characteristics and survival of children and adolescents with germ cell tumors
      treated on this protocol. PATIENTS AND METHODS: From May 1991 to April 2000, 115
      patients (106 assessable patients) were enrolled onto the Brazilian protocol with
      a diagnosis of germ cell tumor. RESULTS: Patients were treated with surgery only
      (n = 35) and chemotherapy (n = 71). Important prognostic factors included stage
      (P = .025), surgical procedure at diagnosis according to resectability (P <
      .032), and abnormal lactate dehydrogenase value at diagnosis (P < .001).
      CONCLUSION: The improvement in survival by the introduction of a standard
      protocol is an important achievement. This is of particular importance for
      smaller institutions with previous limited experience in the treatment of
      childhood germ cell tumors. In addition, the results of a two-agent regimen with
      PE were favorable (5-year overall survival rate is 83.3% for patients in the high
      risk group [n = 36] who received PE v 58.8% for patients in the high-risk
      patients group who received PE plus ifosfamide, vinblastine, and bleomycin [n =
      17; P = .017]). Thus for selected patients, complex three-agent regimens may not
      be necessary to achieve long-term survival, even for some patients with advanced
      disease.

PMID- 19164216
TI  - Myocardial perfusion reserve in ischemic heart disease.

PMID- 19164217
TI  - Improving anti-CD45 antibody radioimmunotherapy using a physiologically based
      pharmacokinetic model.
AB  - Radioimmunotherapy is a method to selectively deliver radioactivity to cancer
      cells via specific antibodies. A strategy to enhance the efficacy of
      radioimmunotherapy is the prior application of unlabeled antibody, resulting in
      an increase in the dose to the target tissue and a decrease in the burden to
      other organs. It was suggested that optimizing this approach might considerably
      improve radioimmunotherapy with anti-CD45 antibody. The present work develops a
      physiologically based pharmacokinetic model to individually determine the optimal
      preload for radioimmunotherapy with the YAML568 anti-CD45 antibody for each
      patient. METHODS: A physiologically based pharmacokinetic model was developed to
      describe the biodistribution of anti-CD45 antibody. The transport of antibody to
      the organs of interest via blood flow, competitive binding of unlabeled and
      labeled antibody, degradation and excretion of antibody, and physical decay were
      included in the model. The model was fitted to the biokinetics data of 5 patients
      with acute myeloid leukemia. On the basis of the estimated parameters,
      simulations for a 0- to 534-nmol preload of unlabeled antibody were conducted and
      the organ residence times were calculated. RESULTS: The measured data could be
      adequately described by the constructed model. The estimated numbers of
      accessible antigens in the respective organ, in nanomoles, were 97+/-33 for red
      marrow, 49+/-24 for liver, 34+/-18 for spleen, 38+/-31 for lymph nodes, and 0.9+/
      0.4 for blood. These ranges indicate high interpatient variability. The optimal
      amount of unlabeled antibody identified by simulations would improve the ratio of
      residence time in red marrow to residence time in liver by a factor of 1.6-2.4.
      CONCLUSION: The efficacy of radioimmunotherapy using anti-CD45 antibody can be
      considerably increased with the presented model. A more selective delivery of
      radioactivity to the target organ and a reduction in the toxicity to normal
      tissue are achieved by determining the optimal preload. Furthermore, the adverse
      effects of radioimmunotherapy might be drastically reduced while saving antibody
      expenses. The validation of the model is ongoing. The model is easily extendible
      and therefore most probably applicable to radioimmunotherapy of other hematologic
      malignancies, such as antibodies targeted to CD20, CD33, or CD66.

PMID- 19164218
TI  - Imaging surrogates of tumor response to therapy: anatomic and functional
      biomarkers.
AB  - This article addresses the current status of quantitative imaging as a surrogate
      biomarker for the assessment of tumor response to therapy with non-small cell
      lung cancer as an example. In addition, the article discusses the limitations of
      conventional response criteria in the new era of molecular-targeted agents for
      cancer treatment; the increasing need for more accurate and early response
      assessment methods, particularly for volumetric CT; new tumor-specific
      radiotracers and molecular imaging technologies; and the future applications of
      molecular imaging with PET for studying various features of cancer metabolism,
      endocrine status, hypoxia, and oncofetal and differentiation antigens.

PMID- 19164219
TI  - Comparison between the prognostic value of left ventricular function and
      myocardial perfusion reserve in patients with ischemic heart disease.
AB  - The purpose of this study was to compare the prognostic value of left ventricular
      ejection fraction (LVEF) and myocardial perfusion reserve (MPR) assessed with PET
      in patients with ischemic heart disease (IHD). Myocardial perfusion is the main
      determinant of left ventricular function in patients with IHD. The prognostic
      value of LVEF has been widely established. In addition, MPR determines survival
      in patients with hypertrophic and dilated cardiomyopathies. In the present study,
      we evaluated whether MPR also determines survival in patients with IHD. METHODS:
      Between 1995 and 2003, 480 consecutive patients with chronic IHD underwent
      dipyridamole stress and rest 13N-ammonia PET to determine MPR. Additionally, 18F
      FDG PET was performed for viability (mismatching defects), infarction (matching
      defects), and left ventricular function assessment. Patients were followed for
      all causes of mortality and major cardiovascular events. RESULTS: In 463 of the
      480 patients, valid MPR could be measured (368 men; mean age, 66+/-11 y; LVEF,
      35%+/-15%). One hundred nineteen patients underwent a PET-driven
      revascularization (67 through percutaneous coronary intervention and 52 through
      coronary artery bypass grafting). The remaining 344 patients were the subject of
      this study. The overall MPR was 1.71+/-0.50 (intertertile boundaries, 1.49 and
      1.84). After adjustment for age and sex, MPR was associated with a hazard ratio
      for cardiac death of 4.11 (95% confidence interval, 2.98-5.67) per SD decrease,
      whereas the risk for LVEF was 2.76 (2.00-3.82) per SD decrease. CONCLUSION:
      Patients with IHD with a low MPR are at high risk of cardiac death. MPR is a more
      sensitive predictor for cardiac death than is LVEF.

PMID- 19164220
TI  - Characterization of PiB binding to white matter in Alzheimer disease and other
      dementias.
AB  - 11C-Pittsburgh Compound B (11C-PiB) PET has demonstrated significantly higher PiB
      retention in the gray matter of Alzheimer disease (AD) patients than in healthy
      controls (HCs). PiB is similarly retained within the white matter of HC and AD
      brains. Although the specificity of PiB for Abeta plaques in gray matter has been
      well described, the nature of PiB binding to white matter remains unclear. In
      this study, we characterized the binding of PiB to human white matter
      homogenates. METHODS: In vitro binding studies were conducted using 3H-PiB (0.1
      500 nM) and white matter brain homogenates (100 microg) from 3 AD patients and 3
      HCs. Nonspecific binding was determined using PiB (1 microM). White matter from
      the same patients was also analyzed by immunofluorescence/immunohistochemistry
      (IF/IHC) microscopy and Western blotting for Abeta expression. White matter
      kinetics were also characterized in vivo through 11C-PiB PET studies in 27 HCs
      and 34 patients with dementia. IF/IHC experiments were conducted on 1 postmortem
      patient with dementia, to compare with the 11C-PiB distribution volume ratio data
      acquired 23 mo earlier. RESULTS: In vitro saturation studies indicated that 3H
      PiB binds nonspecifically to white matter brain homogenates. PiB fluorescence
      staining of AD and HC brain sections was consistent with absence of Abeta in IHC
      staining. Higher gray matter-to-white matter ratios were observed in IHC images
      than in 11C-PiB PET images. CONCLUSION: These studies suggest that PiB binding to
      white matter is mainly nonsaturable and nonspecific and that PiB retention in the
      11C-PiB PET studies is largely attributable to slower PiB white matter kinetics.

PMID- 19164221
TI  - A proposition for the use of radioiodine in WDTC management.

PMID- 19164222
TI  - Radiation dosimetry of beta-amyloid tracers 11C-PiB and 18F-BAY94-9172.
AB  - Beta-amyloid (Abeta) imaging has great potential to aid in the diagnosis of
      Alzheimer disease and the development of therapeutics. The radiation dosimetry of
      Abeta radioligands may influence their application; therefore, we calculated and
      compared the effective doses (EDs) of 11C-PiB and a new 18F-labeled ligand, 18F
      BAY94-9172. METHODS: Attenuation-corrected whole-body scans were performed at 0,
      15, 30, 45, and 60 min after injection of 350+/-28 MBq (mean+/-SD) of 11C-PiB in
      6 subjects and at 0, 20, 60, 120, and 180 min after injection of 319+/-27 MBq of
      18F-BAY94-9172 in 3 subjects. Coregistered CT was used to define volumes of
      interest (VOIs) on the PET images. The source organs were the brain, lungs,
      liver, kidneys, spleen, and vertebrae. The VOIs for the contents of the
      gallbladder, urinary bladder, lower large intestine, upper large intestine, and
      small intestine were also defined. Total activity in each organ at each time
      point was calculated by use of reference organ volumes. The resultant time
      activity curves were fitted with constrained exponential fits, and cumulated
      activities were determined. A dynamic bladder voiding model was used. The
      OLINDA/EXM program was used to calculate the whole-body EDs from the acquired
      data. RESULTS: For 11C-PiB, the highest absorbed doses were in the gallbladder
      wall (44.80+/-29.30 microGy/MBq), urinary bladder wall (26.30+/-8.50
      microGy/MBq), liver (19.88+/-3.58 microGy/MBq), and kidneys (12.92+/-3.37
      microGy/MBq). The ED was 5.29+/-0.66 microSv/MBq. For 18F-BAY94-9172, the highest
      doses were also in the gallbladder wall (132.40+/-43.40 microGy/MBq), urinary
      bladder wall (24.77+/-7.36 microGy/MBq), and liver (39.07+/-8.31 microGy/MBq).
      The ED was 14.67+/-1.39 microSv/MBq. CONCLUSION: The estimated organ doses for
      11C-PiB were comparable to those reported in earlier research. With the doses
      used in published studies (300-700 MBq), the EDs would range from 1.6 to 3.7 mSv.
      The ED of 18F-BAY94-9172 was 30% lower than that of 18F-FDG and, at the published
      dose of 300 MBq, would yield an ED of 4.4 mSv. The dosimetry of both Abeta
      radioligands is suitable for clinical and research applications.

PMID- 19164223
TI  - Evaluation of the brain 5-HT2A receptor binding index in dogs with anxiety
      disorders, measured with 123I-5I-R91150 and SPECT.
AB  - The serotonergic system has been implicated in emotional and cognitive functions
      since early work. In particular, an important role has been attributed to the 5
      HT2A receptor in schizophrenia, depression, eating disorders, and anxiety. The
      aim of the study was to evaluate the involvement of the brain 5-HT2A receptor in
      dogs with severe anxiety disorder, using 123I-5I-R91150 and SPECT. METHODS: SPECT
      was performed with the 5-HT2A receptor-specific radioligand 123I-5I-R91150 to
      determine the 5-HT2A receptor binding index (BI) in the brains of dogs. Sixteen
      dogs with pathologic anxiety problems were compared with 22 normal-behaving
      reference dogs. RESULTS: Lower 5-HT2A receptor BI was found in the left (P=0.001)
      and right (P=0.002) frontal cortices in the group of dogs with anxiety disorders
      than in the reference group. Right (P=0.022) and left (P=0.048) temporocortical
      BIs were also significantly lower in the dogs with anxiety disorders. Finally,
      the BI was significantly lower in the right occipital cortex (P=0.038) of dogs
      with anxiety disorders than in the reference dogs. After correction for multiple
      comparisons (P<0.0056), only the bilateral frontocortical lower BI remained
      significant. CONCLUSION: The findings in this study indicate that the 5-HT2A
      receptor is involved in the pathophysiology of anxiety disorders in dogs. The
      affected brain regions are in concordance with the brain regions involved in
      human anxiety disorders. The acquired data confirm the potential of using the dog
      as a natural model for investigation of the different mechanisms of anxiety
      disorders. In this regard, the use of dogs may contribute to the development of
      novel treatment approaches and new drugs for veterinary and human use.

PMID- 19164224
TI  - Pregnancy outcome after 131I therapy.

PMID- 19164225
TI  - 131I SPECT/CT in the follow-up of differentiated thyroid carcinoma: incremental
      value versus planar imaging.
AB  - Planar 131I scintigraphy is routinely used to detect radioiodine-avid metastases
      of differentiated thyroid carcinoma (DTC). However, the modality has limitations,
      such as low sensitivity and lack of anatomic landmarks. We investigated whether
      SPECT with integrated low-dose CT may have additional value over planar imaging
      in detecting residue and metastases in DTC patients. METHODS: We studied 117
      consecutive thyroidectomized DTC patients. On 2 different hybrid dual-head gamma
      cameras (55 patients on one camera and 62 on the other), 108 patients underwent
      131I diagnostic imaging and SPECT/CT, and 9 underwent posttherapeutic 131I planar
      imaging and SPECT/CT. We assigned an incremental value to SPECT/CT when it
      provided better identification and interpretation of the foci of radioiodine
      uptake, more correct anatomic localization and characterization, and precise
      differentiation between tumor lesions and physiologic uptake. RESULTS: Planar
      imaging showed 116 foci of uptake in 52 of 117 patients, and SPECT/CT showed 158
      foci in 59 of 117 patients, confirming all foci seen on planar imaging but
      identifying an additional 28 occult foci in 10 of 52 patients. Fourteen occult
      foci were shown on SPECT/CT in 7 further patients whose planar imaging findings
      were negative. SPECT/CT correctly characterized 48 foci unclear on planar
      imaging, also defining location and extent. SPECT/CT was a determinant in
      classifying as neoplastic those foci for which planar imaging seemed to exclude
      malignancy, discriminating between residue and lymph node metastases in the neck,
      some of which were adjacent to salivary glands and had been missed on planar
      imaging. SPECT/CT also showed occult lesions in the mediastinum, abdomen, and
      pelvis and identified small bone metastases unsuspected on planar imaging.
      Globally, SPECT/CT had an incremental value over planar imaging in 67.8% of
      patients, modified therapeutic management in 35.6% of positive cases, and avoided
      unnecessary treatment in 20.3% of patients with only single benign lesions or
      physiologic uptake. CONCLUSION: 131I SPECT/CT improved planar data
      interpretation, showing a higher number of DTC lesions, more precisely localizing
      and characterizing DTC foci, and more correctly differentiating between
      physiologic uptake and metastases, thus permitting the most appropriate
      therapeutic approach to be chosen. A wider use of this method is suggested
      complementary to planar imaging in selected DTC patients.

PMID- 19164226
TI  - Impact of intravenous insulin on 18F-FDG PET in diabetic cancer patients.
AB  - The aims of this study were to evaluate the effectiveness of a standardized
      insulin protocol in reducing glycemia, review (18)F-FDG biodistribution with such
      a protocol, and assess its clinical impact. METHODS: Sixty-three patients with
      glycemia greater than 10 mmol/L received insulin doses intravenously according to
      a standardized protocol. One hundred six consecutive euglycemic patients (<6.2
      mmol/L) served as controls. (18)F-FDG biodistribution was evaluated by 2
      experienced PET readers on a 5-point visual scale based on muscular uptake. The
      63 patients who received insulin were divided into insulin subgroup A, with
      adequate biodistribution (score 0, 1, or 2) and insulin subgroup B, with altered
      biodistribution (score 3 or 4). 18F-FDG biodistribution was also evaluated
      semiquantitatively by standardized uptake value (SUV) measurements over the
      liver, gluteal muscles, and myocardium. Clinical impact (complications and
      diagnostic accuracy) was assessed by follow-up. RESULTS: Glycemia decreased from
      13+/-2 to 7+/-2 mmol/L after insulin injection. Images showed significantly more
      muscular uptake in patients who received insulin than in the control group
      (scores 1.6+/-1.5 vs. 0.4+/-0.6, P<0.05). Twenty-five percent of insulin patients
      studied had altered biodistribution (insulin subgroup B). The two most important
      factors increasing muscular uptake were the time interval between insulin and 18F
      FDG injection (mean in insulin subgroup A, 80.2+/-17 min; mean in insulin
      subgroup B, 65.7+/-10 min; P<0.01) and the glycemia interval decrease after
      insulin injection (mean in insulin subgroup A, 5.3+/-2.6 mmol/L; mean in insulin
      subgroup B, 7.6+/-1.8 mmol/L; P<0.01). In insulin subgroup B, mean hepatic SUV
      was lower (1.3+/-0.4 vs. 2.1+/-0.4, P<0.01) and mean muscular SUV was higher
      (1.8+/-0.1 vs. 0.9+/-0.01, P<0.01). Of the 63 patients who received insulin, 6
      had hypoglycemia, but only 2 were symptomatic. No patient had severe
      complications causing permanent disability. CONCLUSION: A standardized protocol
      of intravenous insulin before 18F-FDG injection in diabetic cancer patients was
      safe and effective in reducing glycemia. Acceptable 18F-FDG biodistribution was
      obtained in 75% of patients receiving insulin. In addition to visually increased
      muscular uptake, low hepatic 18F-FDG uptake was a good indicator of altered
      biodistribution.

PMID- 19164228
TI  - Evaluation of D-18F-FMT, 18F-FDG, L-11C-MET, and 18F-FLT for monitoring the
      response of tumors to radiotherapy in mice.
AB  - O-18F-fluoromethyl-D-tyrosine (D-18F-FMT) is a promising novel agent for tumor
      imaging by PET. The aim of this study was to evaluate the potential of D-18F-FMT
      and the other conventional ligands used for tumor imaging, namely, 18F-FDG, L-11C
      methionine (L-11C-MET), and 3'-deoxy-3'-18F-fluorothymidine (18F-FLT), as a PET
      ligand for monitoring early responses to radiotherapy in tumor-bearing mice.
      METHODS: C3H/HeN mice inoculated with murine squamous cell carcinomas were
      treated with a single dose of x-ray irradiation at 2, 6, 20, or 60 Gy. Tumor
      uptake of each ligand was examined 1, 3, and 7 d after the irradiation. RESULTS:
      Tumor uptake of D-18F-FMT was decreased on day 1 after irradiation at 6, 20, or
      60 Gy, and the decrease persisted until day 7. Tumor uptake of 18F-FDG was
      elevated on days 1 and 3 after irradiation at 2, 6, or 20 Gy, followed by a
      decrease in uptake on day 7 in mice irradiated at 20 or 60 Gy. Decreased tumor
      uptake of L-11C-MET was observed only on day 3 after the irradiation. Decreased
      tumor uptake of 18F-FLT was detected on day 1 after irradiation at 2, 6, 20, or
      60 Gy; thereafter, the dose-dependent decrease in uptake was no longer seen. Only
      for D-18F-FMT were significant positive correlations found between ligand uptake
      at all the time points examined and tumor volume on day 14 after various doses of
      irradiation. CONCLUSION: The findings suggest that D-18F-FMT is a promising PET
      ligand for early-phase detection and prediction of the effects of radiation
      therapy.

PMID- 19164230
TI  - PET for the evaluation of solitary pulmonary nodules.

PMID- 19164229
TI  - Retrospective study of 18F-FDG PET/CT in the diagnosis of inflammatory breast
      cancer: preliminary data.
AB  - Our objective was to retrospectively evaluate 18F-FDG PET/CT in the initial
      staging of inflammatory breast cancer (IBC). METHODS: The institutional review
      board waived informed consent and approved this study, which was compliant with
      the Health Insurance Portability and Accountability Act. The cases of 41 women
      with a mean age of 50 y (range, 25-71 y) and newly diagnosed IBC who underwent
      18F-FDG PET/CT at diagnosis were retrospectively reviewed. All PET/CT images were
      analyzed visually and semiquantitatively by 2 physicians. The maximum
      standardized uptake value in the primary breast, regional nodes (axillary,
      subpectoral, supraclavicular, internal mammary), and extranodal regions was
      documented. The accuracy of PET/CT image interpretation was assessed by
      histopathologic analysis, if available; concurrent or subsequent imaging findings
      (contrast-enhanced CT, contrast-enhanced MRI, sonography, or PET/CT follow-up);
      or clinical follow-up. RESULTS: All patients presented with unilateral IBC.
      PET/CT showed hypermetabolic uptake in the skin in all patients, in the affected
      breast in 40 (98%), in the ipsilateral axillary nodes in 37 (90%), and in the
      ipsilateral subpectoral nodes in 18 (44%). Twenty patients (49%) were found to
      have distant metastases at staging, 7 (17%) of whom were not known to have
      metastases before undergoing PET/CT. Disease sites included bone, liver,
      contralateral axilla, lung, chest wall, pelvis, and the subpectoral,
      supraclavicular, internal mammary, mediastinal, and abdominal nodes. CONCLUSION:
      PET/CT should be considered in the initial staging of IBC, as the technique
      provided valuable information on locoregional and distant disease in this
      preliminary retrospective study.

PMID- 19164233
TI  - Multimodality cardiac stress testing: combining real-time 3-dimensional
      echocardiography and myocardial perfusion SPECT.
AB  - Early experience is described in implementing a new multimodality stress test for
      accurate correlation of complementary functional and perfusion information from
      real-time 3-dimensional (3D) echocardiography and SPECT, respectively. The
      proposed new multimodality stress test has the potential for simultaneously
      improving sensitivity and specificity in the detection of early coronary artery
      disease (CAD). METHODS: Pre- and poststress real-time 3D echocardiography and
      SPECT images were acquired in 20 patients referred for CAD evaluation and
      processed using previously developed algorithms for automatic fusion and
      quantitative analysis of myocardial function and perfusion. All cases of CAD were
      diagnosed by reviewing quantitatively analyzed fused images, using newly
      developed software. RESULTS: Real-time 3D echocardiography, SPECT, advance
      processing, and image review were successfully performed in all 20 patients.
      Compared with the angiographic findings in 12 patients, diagnosis based on fused
      images correctly identified 13 of 13 diseased arteries, compared with 11 of 13
      identified by SPECT and 6 of 13 identified by echocardiography-based analysis.
      CONCLUSION: The results suggest the feasibility and potential effectiveness of
      novel multimodality stress testing.

PMID- 19164235
TI  - An improved method for automatic segmentation of the left ventricle in myocardial
      perfusion SPECT.
AB  - This study describes and validates a new method for automatic segmentation of
      left ventricular mass (LVM) in myocardial perfusion SPECT (MPS) images. This is
      important for estimating the size of a perfusion defect as percentage of the left
      ventricle. METHODS: A total of 101 patients with known or suspected coronary
      artery disease underwent both rest and stress MPS and MRI. A new automated
      algorithm was trained in 20 patients (40 MPS studies) and tested in 81 patients
      (162 MPS studies). The algorithm, which segmented the left ventricle in the MPS
      images, is based on Dijkstra's algorithm and finds an optimal mid-mural line
      through the left ventricular wall. From this line, the endocardium and epicardium
      are identified on the basis of an individually estimated wall thickness and
      signal intensity. The algorithm was validated by comparing LVM in both stress and
      rest MPS, with LVM of the manually segmented left ventricle from MRI as the
      reference standard. For comparison, LVM was quantified using the software
      quantitative perfusion SPECT (QPS). RESULTS: The mean difference+/-SD in LVM
      between MPS and MRI was lower for the new method (6%+/-15% LVM) than for QPS
      (18%+/-19% LVM) for both mean difference (P<0.001) and SD (P=0.015). Linear
      regression analysis of LVM, comparing MPS and MRI, yielded R2=0.83 using the new
      method and R2=0.80 using QPS. Interstudy variability, measured as the coefficient
      of variance between rest MPS and stress MPS, was 6% for both the new method and
      QPS. Both the new algorithm and QPS systematically overestimated LVM in hearts
      with thin myocardium and underestimated LVM in hearts with thick myocardium.
      CONCLUSION: The new segmentation algorithm quantifies LVM with a significantly
      lower bias and variability than does the commercially available QPS software,
      when compared to manually segmented LVM by MRI. This makes the new algorithm an
      attractive method to use for estimating the size of the perfusion defect when
      expressing it as percentage of the left ventricle. This study shows that
      inaccurate estimation of wall thickness is the main source of error in automatic
      segmentation.

PMID- 19164236
TI  - PET and macro- and microautoradiographic studies combined with
      immunohistochemistry for monitoring rat intestinal ulceration and healing
      processes.
AB  - 18F-FDG PET is used mainly in clinical settings for imaging focal cancer sites,
      but the usefulness of the modality in imaging gastrointestinal ulcers has not
      been established. We investigated whether PET can be used for noninvasive
      monitoring of indomethacin-induced small-intestine ulceration. METHODS:
      Intestinal ulcers were induced in rats by subcutaneous administration of
      indomethacin. An 18F-FDG PET scan was obtained at 1, 2, and 7 d after
      indomethacin administration. 18F-FDG uptake in the small intestine was quantified
      by gamma-counting, and macro- and microautoradiographic studies were performed to
      determine the site of 18F-FDG uptake in tissue and at the cellular level.
      RESULTS: Ulcers observed in the intestine (mainly in the ileum) 1-4 d after
      indomethacin administration were most severe at 1 d after administration and were
      almost healed at day 7. The PET study showed increased 18F-FDG uptake in the
      intestine correlating to the severity of ulceration, returning to the basal level
      on day 7. Ex vivo imaging and gamma-counting showed that these regions of high
      uptake corresponded to regions of ulceration. A microautoradiographic study
      combined with immunohistochemistry revealed heavy accumulation of 18F-FDG in
      inflammatory cells containing peroxidase on day 1 and in cells forming
      granulation tissue (alpha-smooth muscle actin-positive myofibroblasts and ED2
      positive macrophages) on days 2-4 in and around ulcers. Proliferating (Ki67
      immunopositive) intestinal crypt cells were also densely labeled with 18F-FDG in
      intact intestinal tissue taken from the indomethacin-treated and the control
      animals. CONCLUSION: Our experimental data suggest that 18F-FDG PET may be useful
      for evaluating the occurrence of small-intestine ulcers. Ulceration could be
      visualized early by the prominent uptake of 18F-FDG by inflammatory cells and by
      the formation of granulation tissue by cells in and around ulcers.

PMID- 19164237
TI  - Effect of patient morphology on dosimetric calculations for internal irradiation
      as assessed by comparisons of Monte Carlo versus conventional methodologies.
AB  - Dosimetric calculations are performed with an increasing frequency before or
      after treatment in targeted radionuclide therapy, as well as for radiation
      protection purposes in diagnostic nuclear medicine. According to the MIRD
      committee formalism, the mean absorbed dose to a target is given by the product
      of the cumulated activity and a dose-conversion factor, known as the S factor.
      Standard S factors have been published for mathematic phantoms and for unit
      density spheres. The accuracy of the results from the use of these S factors is
      questionable, because patient morphology can vary significantly. The aim of this
      work was to investigate differences between patient-specific dosimetric results
      obtained using Monte Carlo methodology and results obtained using S factors
      calculated on standard models. METHODS: The CT images of 9 patients, who ranged
      in size, were used. Patient-specific S factors for 131I were calculated with the
      MCNPX2.5.0 Monte Carlo code using a tool for personalized internal dose
      assessment, OEDIPE; standard S factors from OLINDA/EXM were compared against the
      patient-specific S factors. Furthermore, realistic biodistributions and cumulated
      activities for normal organs and tumors were used, and mean organ- and tumor
      absorbed doses calculated with OEDIPE and OLINDA/EXM were compared. RESULTS: The
      ratio of the standard and the patient-specific S factors were between 0.49 and
      1.84 for a target distant from the source for 4 organs and 2 tumors studied as
      source and targets. For the case of self-irradiation, the equivalent ratio ranged
      between 0.45 and 2.47 and between 1.00 and 1.06 when mass correction was applied.
      Differences in mean absorbed doses were as high as 140% when realistic cumulated
      activity values were used. These values decreased to less than 26% in all cases
      studied when mass correction was applied to the self-irradiation given by
      OLINDA/EXM. CONCLUSION: Standard S factors can yield mean absorbed doses for
      normal organs or tumors with a reasonable accuracy (26% for the cases studied) as
      compared with absorbed doses calculated with Monte Carlo, provided that they have
      been corrected for mass.

PMID- 19164238
TI  - Myocardial beta-adrenergic receptor density assessed by 11C-CGP12177 PET predicts
      improvement of cardiac function after carvedilol treatment in patients with
      idiopathic dilated cardiomyopathy.
AB  - We evaluated whether myocardial beta-adrenergic receptor (beta-AR) density, as
      determined by 11C-CGP12177 PET, could predict improvement of cardiac function by
      beta-blocker carvedilol treatment in patients with idiopathic dilated
      cardiomyopathy (IDC). METHODS: Ten patients with IDC (left ventricular ejection
      fraction [LVEF]<45%) were studied. Myocardial beta-AR density was estimated using
      11C-CGP12177 PET before treatment with carvedilol. Changes of LVEF in response to
      dobutamine infusion (DeltaLVEF-dobutamine) were also measured by
      echocardiography. Changes of LVEF (DeltaLVEF-carvedilol) were evaluated after 20
      mo of carvedilol treatment. RESULTS: Baseline myocardial beta-AR density
      significantly correlated with DeltaLVEF-carvedilol (r=-0.88, P<0.001). In
      contrast, DeltaLVEF-dobutamine did not correlate with DeltaLVEF-carvedilol
      (P=0.65). Myocardial beta-AR density was the significant multivariate independent
      predictor of DeltaLVEF-carvedilol (beta=-0.88, P<0.001) among univariate
      predictors, including functional class (r=0.76, P<0.05), plasma norepinephrine
      (r=0.85, P<0.01), LVEF (r=-0.64, P<0.05), and age as confounding factors.
      Furthermore, myocardial beta-AR density was significantly correlated with plasma
      norepinephrine (r=-0.79, P<0.01) and LVEF (r=0.70, P<0.05). CONCLUSION:
      Myocardial beta-AR density is more tightly related to improvement of LVEF
      carvedilol than is cardiac contractile reserve in patients with IDC. Patients
      with decreased myocardial beta-AR have higher resting adrenergic drive, as
      reflected by plasma norepinephrine, and may receive greater benefit from being
      treated by antiadrenergic drugs.

PMID- 19164239
TI  - PET-based biodistribution and radiation dosimetry of epidermal growth factor
      receptor-selective tracer 11C-PD153035 in humans.
AB  - The present study estimated the biodistribution and radiation-absorbed dose of
      epidermal growth factor receptor (EGFR) radioligand 11C-PD153035 in whole-body
      PET examinations of healthy volunteers. METHODS: Two-dimensional whole-body PET
      was performed on 9 subjects after injection of 11C-PD153035 at 329.3+/-77.8 MBq
      (mean+/-SD). A total of 12 frames were acquired for approximately 90 min in 7
      segments of the body. Regions of interest were drawn on PET images of source
      organs. Residence time was calculated as the area under the time-activity curve.
      Radiation dosimetry was calculated from organ residence time by use of MIRDOSE3
      software. RESULTS: The renal and hepatobiliary systems played important roles in
      11C-PD153035 excretion from the body, accounting for the excretion of
      approximately 23% and 19% of the injected radioactivity, respectively. Blood-pool
      activity was only moderate and declined over time. Tracer accumulation in the
      lungs, bone marrow, and muscles was slight, resulting in low background activity
      in the chest. The organs with the highest radiation-absorbed doses were the
      urinary bladder and the gallbladder; the effective doses were 6.08E-02+/-1.85E-02
      and 2.40E-02+/-8.01E-03 mGy/MBq, respectively. The effective dose equivalent was
      7.43E-03+/-1.10E-03 mSv/MBq, and the dose-limiting organ was the urinary bladder.
      CONCLUSION: On the basis of the estimated absorbed dose, 11C-PD153035 displayed a
      favorable radiation dose profile in humans and therefore could be used in
      multiple PET examinations of the same subject per year. 11C-PD153035 is a
      promising ligand for the investigation of EGFR in humans, especially in chest
      tumors such as non-small cell lung cancer.

PMID- 19164240
TI  - Expanding the versatility of cardiac PET/CT: feasibility of delayed contrast
      enhancement CT for infarct detection in a porcine model.
AB  - It has recently been suggested that, similar to MRI, CT can be used to detect
      infarcts at high resolution by delayed myocardial contrast enhancement. In
      cardiac PET/CT, this ability to detect infarcts may increase the versatility and
      integrative potential of PET and CT study components. We sought to determine the
      feasibility of delayed CT-enhancement in the PET/CT environment and compared it
      with PET-defined rest perfusion for the measurement of infarct size. METHODS:
      Experimental myocardial infarction was induced in 10 young farm pigs by occlusion
      and reperfusion of the left anterior descending coronary artery. After 4-6 wk,
      the animals underwent 64-slice PET/CT. Rest perfusion was measured by 13N-ammonia
      PET. Then, 120 mL of contrast were injected, and retrospectively gated helical CT
      was performed for angiography and after 1.5-, 5-, 10-, and 15-min delays. Two
      days later, 6 pigs again underwent contrast-enhanced CT, using a low-radiation
      dose approach (prospective gating and thicker slices as used for clinical calcium
      scoring) and the same delay times. Polar maps of PET perfusion and CT myocardial
      enhancement were created for further analysis. RESULTS: CT Hounsfield units (HUs)
      in the infarct area started to exceed those of arterial blood at 5-10 min after
      contrast injection, and the ratios of infarcted myocardium to remote myocardium
      and of infarcted myocardium to blood plateaued at around 1.9 and 1.2 between 10
      and 15 min. Excellent agreement between high- and low-dose CT acquisitions
      (R=0.87, P<0.001) was demonstrated. At 10 min, CT infarct size (area with HU>3.5
      SDs from remote) was 30%+/-8% of the left ventricle, using the low-dose approach.
      The PET perfusion defect size (area with uptake<60% of the left ventricular
      maximum) was comparable at 31%+/-8% of the left ventricle (range, 17%-44%). Using
      a 16-segment myocardial model, we showed an excellent inverse relationship
      between regional ammonia retention and contrast enhancement (R=-0.93, P<0.001).
      CONCLUSION: In our animal model, infarct size can be measured accurately and
      reproducibly using cardiac PET/CT with delayed CT-enhancement. For measurement, a
      low-dose, prospectively gated acquisition was comparable to higher-dose spiral
      CT. These results provide a rationale for further clinical work to explore
      whether delayed CT-enhancement can improve the accuracy of myocardial viability
      assessment, substitute for rest studies in perfusion imaging, or improve
      localization of PET-derived molecular signals.

PMID- 19164241
TI  - Affibody molecules for epidermal growth factor receptor targeting in vivo:
      aspects of dimerization and labeling chemistry.
AB  - Noninvasive detection of epidermal growth factor receptor (EGFR) expression in
      malignant tumors by radionuclide molecular imaging may provide diagnostic
      information influencing patient management. The aim of this study was to evaluate
      a novel EGFR-targeting protein, the ZEGFR:1907 Affibody molecule, for
      radionuclide imaging of EGFR expression, to determine a suitable tracer format
      (dimer or monomer) and optimal label. METHODS: An EGFR-specific Affibody
      molecule, ZEGFR:1907, and its dimeric form, (ZEGFR:1907)2, were labeled with
      111In using benzyl-diethylenetriaminepentaacetic acid and with 125I using p
      iodobenzoate. Affinity and cellular retention of conjugates were evaluated in
      vitro. Biodistribution of radiolabeled Affibody molecules was compared in mice
      bearing EGFR-expressing A431 xenografts. Specificity of EGFR targeting was
      confirmed by comparison with biodistribution of non-EGFR-specific counterparts.
      RESULTS: Head-to-tail dimerization of the Affibody molecule improved the
      dissociation rate. In vitro, dimeric forms demonstrated superior cellular
      retention of radioactivity. For both molecular set-ups, retention was better for
      the 111In-labeled tracer than for the radioiodinated counterpart. In vivo, all
      conjugates accumulated specifically in xenografts and in EGFR-expressing tissues.
      The retention of radioactivity in tumors was better in vivo for dimeric forms;
      however, the absolute uptake values were higher for monomeric tracers. The best
      tracer, 111In-labeled ZEGFR:1907, provided a tumor-to-blood ratio of 100 (24 h
      after injection). CONCLUSION: The radiometal-labeled monomeric Affibody molecule
      ZEGFR:1907 has a potential for radionuclide molecular imaging of EGFR expression
      in malignant tumors.

PMID- 19164243
TI  - Detection of Alzheimer pathology in vivo using both 11C-PIB and 18F-FDDNP PET.
AB  - 11C-Pittsburgh Compound-B (11C-PIB) and 18F-(2-(1-{6-[(2
      [18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) (18F-FDDNP) have been
      developed as PET tracers for in vivo imaging of pathology in Alzheimer's disease
      (AD). The purpose of this study was to directly compare these tracers in patients
      with AD, patients with mild cognitive impairment (MCI), and healthy controls.
      METHODS: Paired 11C-PIB and 18F-FDDNP scans were acquired in 14 patients with AD,
      11 patients with amnestic MCI, and 13 controls. For both tracers, parametric
      images of binding potential (BPND) were generated. Global cortical BPND was
      assessed using ANOVA. In addition, regional patterns of BPND were compared
      between diagnostic groups using ANOVA for repeated measures. RESULTS: Global
      cortical BPND of 11C-PIB showed higher binding in patients with AD than in
      controls and patients with MCI. 18F-FDDNP uptake was higher in patients with AD
      than in controls, but MCI could not be distinguished from AD or from controls.
      Global BPND values of both tracers were moderately correlated (r=0.45; P=0.005).
      In MCI, BPND of 11C-PIB showed a bimodal distribution, whereas values for 18F
      FDDNP were more widespread, with more MCI patients demonstrating increased
      uptake. Regional 11C-PIB binding showed different patterns across diagnostic
      groups, as AD patients showed an overall increase in binding, with the lowest
      binding in the medial temporal lobe. With 18F-FDDNP, patterns were similar across
      diagnostic groups. For all groups, highest values were observed in the medial
      temporal lobe. CONCLUSION: Differences in BPND between patients with AD, patients
      with MCI, and controls were more pronounced for 11C-PIB. The difference in
      regional binding, the moderate correlation, and the discrepant findings in MCI
      suggest that they measure related, but different, characteristics of the disease.

PMID- 19164242
TI  - Magnetic tagging of therapeutic cells for MRI.
AB  - Transplantation of stem cells or immune cells has shown promise for the treatment
      of several diseases. Monitoring magnetically labeled cells with MRI has furthered
      our understanding of cellular migration and the pathophysiology of diseases in
      experimental models. These studies should pave the way for guiding clinical
      trials using cell-based therapies. This review briefly describes the various
      methods used to label and track cells with MRI and the potential for such methods
      to translate to human applications.

PMID- 19164246
TI  - Intraperitoneal administration of drugs in peritoneal dialysis patients: a review
      of compatibility and guidance for clinical use.
AB  - Peritoneal dialysis (PD) is an effective home-based therapy for end-stage renal
      failure. Intraperitoneal administration of drugs to PD patients is particularly
      important for the treatment of peritonitis. Clinicians need to know that the
      administered drug is compatible with both the PD solution and its container. A
      detailed literature search on drug compatibility and stability was performed and
      results of all published stability studies are presented for all drugs, PD
      solutions, and containers studied. These data will aid clinicians managing PD
      patients and provide a resource to demonstrate which drugs have been shown to be
      stable in various PD solutions and solution containers. This is important
      information to assist clinicians in applying effective treatments, in particular,
      for peritonitis.

PMID- 19164244
TI  - Derivation of a compartmental model for quantifying 64Cu-DOTA-RGD kinetics in
      tumor-bearing mice.
AB  - Radiolabeled arginine-glycine-aspartate (RGD) peptides are increasingly used in
      preclinical and clinical studies to assess the expression and function of the
      alphavbeta3 integrin, a cellular adhesion molecule involved in angiogenesis and
      tumor metastasis formation. To better understand the PET signal obtained with
      radiolabeled RGD peptides, we have constructed a compartmental model that can
      describe the time-activity curves in tumors after an intravenous injection.
      METHODS: We analyzed 60-min dynamic PET scans obtained with 64Cu-1,4,7,10
      tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-RGD in 20 tumor
      bearing severe combined immunodeficient (SCID) mice after a bolus dose (18,500
      kBq [500 microCi]), using variations of the standard 2-compartment (4k) tissue
      model augmented with a compartment for irreversible tracer internalization.
      alphavbeta3 binding sites were blocked in 5 studies with a coinjection of cold
      peptide. In addition, 20 h after injection, static PET was performed on 9 of 20
      mice. We fitted 2k (k3=k4=0), 3k (k4=0), 4k, and 4kc (k4=constant) models to the
      PET data and used several criteria to determine the best model structure for
      describing 64Cu-DOTA-RGD kinetics in mice. Akaike information criteria (AIC),
      calculated from model fits and the ability of each model to predict tumor
      concentration 20 h after tracer injection, were considered. RESULTS: The 4kc
      model has the best profile in terms of AIC values and predictive ability, and a
      constant k4 is further supported by Logan-Patlak analysis and results from
      iterative Bayesian parameter estimation. The internalization compartment allows
      quantification of the putative tracer internalization rate for each study, which
      is estimated here to be approximately an order of magnitude less than k3 and thus
      does not confound the apparent specific binding of the tracer to the tumor
      integrin during the first 60 min of the scan. Analysis of specific (S) and
      nonspecific or nondisplaceable (ND) binding using fitted parameter values showed
      that the 4kc model provided expected results when comparing alphavbeta3 blocked
      and nonblocked studies. That is, specific volume of distribution,
      [VS=(K1k3)/(k2k4)], is much higher than is nondisplaceable volume of
      distribution, [VND=(K1/k2)], in nonblocking studies (2.2+/-0.6 vs. 0.85+/-0.14);
      VS and VND are about the same in the blocking studies (0.46+/-1.6 vs. 0.56+/
      0.09). Also, the ratio of static tumor and plasma measurements at 60 and 10 min
      [CT(60)/CP(10)] is highly correlated (RS=0.92) to tumor VS. CONCLUSION: We have
      developed and tested a compartmental model for use with the 64Cu-DOTA-RGD PET
      tracer and demonstrated its potential as a tool for analysis and design of
      preclinical and clinical imaging studies.

PMID- 19164247
TI  - Heparin and the peritoneal membrane.

PMID- 19164248
TI  - Ultrafiltration and the buffer: one more interaction to consider?

PMID- 19164249
TI  - Clues at the scene of the crime: sudden death in dialysis patients.

PMID- 19164250
TI  - Long-term intervention with heparins in a rat model of peritoneal dialysis.
AB  - BACKGROUND: Peritoneal dialysis (PD) is associated with functional and structural
      alterations of the peritoneal membrane, particularly new vessel formation and
      fibrosis. In addition to anticoagulant effects, heparin displays anti
      inflammatory and angiostatic properties. Therefore, the effects of administration
      of heparins on function and morphology of the peritoneal membrane were studied in
      a rat PD model. METHODS: Rats received 10 mL conventional PD fluid (PDF) daily,
      with or without the addition of unfractionated heparin (UFH) or low molecular
      weight heparin (LMWH) in the PDF (1 mg/10 mL intraperitoneally) via a mini access
      port. Untreated rats served as controls. After 5 weeks, a 90-minute functional
      peritoneal transport test was performed and tissues and peritoneal leukocytes
      were taken. RESULTS: PD treatment induced loss of ultrafiltration (p<0.01), a
      twofold increase in glucose absorption (p<0.03), increased urea transport
      (p<0.02), and loss of sodium sieving (p<0.03), which were also found in the
      PDF+heparin groups. Increased peritoneal cell influx and hyaluronan production
      (p<0.02) as well as an exchange of mast cells and eosinophils for neutrophils
      after PD treatment were observed in PD rats; addition of heparin did not affect
      those changes. Mesothelial regeneration, submesothelial blood vessel and matrix
      formation, and accumulation of tissue macrophages were seen in PD animals.
      Spindle-shaped vimentin-positive and cytokeratin-negative cells indicated either
      partial injury and denudation of mesothelial cells or epithelial-to-mesenchymal
      transition. Neither UFH nor LMWH affected any of these morphological changes.
      CONCLUSION: Within 5 weeks, PD treatment induces a chronic inflammatory condition
      in the peritoneum, evidenced by high transport, leukocyte recruitment, tissue
      remodeling, and induction of spindle-shaped cells in the mesothelium. Addition of
      LMWH or UFH to the PDF did not prevent these adverse PDF-induced peritoneal
      changes.

PMID- 19164251
TI  - Substituting citrate for lactate in peritoneal dialysis fluid improves
      ultrafiltration in rats.
AB  - BACKGROUND: Exposure to peritoneal dialysis (PD) fluid induces an inflammatory
      response in the peritoneal cavity. Blockers of complement and coagulation have
      improved ultrafiltration in animal models of PD. Citrate is a clinically
      established anticoagulant that also blocks complement activation. OBJECTIVE: The
      aim of the present study was to evaluate the effects on ultrafiltration of a
      gradual substitution of citrate for lactate in an experimental model of PD.
      METHODS: Fractions (0, 5, 10, and 15 mmol/L) of the 40 mmol/L lactate buffer of
      filter-sterilized 2.5% glucose PD fluid were replaced by citrate. The modified
      fluids were compared in a rat model of single PD fluid exposure through an
      indwelling catheter. The initial kinetics of citrate and ionized calcium were
      evaluated in separate, single, short time dwell experiments. RESULTS: Replacing
      10 and 15 mmol/L of the lactate buffer by sodium citrate significantly increased
      osmotic ultrafiltration (by 24.7%+/-7.7% at 10 mmol/L), net ultrafiltration, and
      glucose retention at 4 hours of dwell time in the rat model. Osmotic
      ultrafiltration was significantly correlated to citrate concentration and glucose
      concentration. Citrate was rapidly eliminated from the peritoneal cavity,
      concentrations falling to less than half in 1 hour and concentrations of calcium
      ions concomitantly normalized. CONCLUSIONS: Substituting citrate for lactate
      induced a dose-dependent increase in ultrafiltration. Mechanisms probably involve
      the relation between diffusion and ultrafiltration, leading to increased glucose
      retention. The increase in ultrafiltration was quantitatively important at a
      citrate concentration (10 mmol/L) that is compatible with clinical applications
      of citrate.

PMID- 19164252
TI  - 3,4-dideoxyglucosone-3-ene induces apoptosis in human peritoneal mesothelial
      cells.
AB  - OBJECTIVE: Glucose degradation products (GDPs) are formed during heat
      sterilization and storage of peritoneal dialysis (PD) fluids. 3,4
      dideoxyglucosone-3-ene (3,4-DGE) has been identified as the most bioreactive GDP.
      3,4-DGE induces apoptosis in leukocytes and renal tubular epithelial cells. Our
      aim was to evaluate the apoptotic effects of 3,4-DGE on human peritoneal
      mesothelial cells (HPMCs). METHODS: Primary cultured HPMCs were treated with 25
      or 50 micromol/L 3,4-DGE. MTT assay was used to determine cell viability.
      Apoptosis was measured using TUNEL assay and flow cytometry. Expressions of
      procaspase-3, Bax, and Bcl-2 were estimated by Western blot. Activity of caspase
      3 was measured and the effect of the caspase inhibitor zVAD-fmk (Z-Val-Ala-DL-Asp
      fluoromethylketone) was evaluated by TUNEL assay. RESULTS: 3,4-DGE treatment
      accelerated cell death in HPMCs in a dose- and time-dependent manner. Treatment
      with 3,4-DGE (25 and 50 micromol/L) significantly increased apoptosis compared to
      control (p<0.05 and p<0.01 respectively) by TUNEL assay. Flow cytometry showed
      treatment with 50 micromol/L 3,4-DGE significantly increased apoptosis compared
      to control (p<0.05). Decreased expression of procaspase-3 and increased activity
      of caspase-3 were observed in the presence of 50 micromol/L 3,4-DGE compared to
      control and 25 micromol/L 3,4-DGE (p<0.05). 3,4-DGE-induced HPMC apoptosis was
      decreased after pretreatment with the pan-caspase inhibitor zVAD-fmk in the 50
      micromol/L 3,4-DGE-treated group (p<0.001). The ratio of Bcl-2 to Bax expression
      was decreased in the 25 micromol/L and the 50 micromol/L 3,4-DGE-treated groups
      compared to control (p<0.05). CONCLUSIONS: 3,4-DGE promotes apoptosis in HPMCs by
      a caspase-related mechanism.

PMID- 19164253
TI  - Stability of tobramycin and ceftazidime in icodextrin peritoneal dialysis
      solution.
AB  - PURPOSE: The data describing the compatibility of tobramycin and ceftazidime in
      icodextrin-based peritoneal dialysis (PD) solution is limited. The objective of
      this study was to assess the chemical stability of tobramycin and ceftazidime in
      icodextrin PD solution in polyvinyl chloride containers. METHODS: Commercially
      available 2-L bags of icodextrin 7.5% PD solution were used for each sample. Nine
      tobramycin study samples were prepared by adding 80 mg tobramycin HCl to each
      bag. Nine ceftazidime samples were prepared by adding 1000 mg ceftazidime to each
      bag. Three bags of tobramycin-icodextrin solution were stored under each of the
      following conditions: refrigeration (4 degrees C), room temperature (25 degrees
      C), and body temperature (37 degrees C). Three bags of ceftazidime-icodextrin
      solution were also stored at each of the respective temperatures. Samples were
      withdrawn from each bag immediately after preparation and at predetermined
      intervals (1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 336 hours after
      preparation). Solutions were visually inspected for precipitation, cloudiness,
      and discoloration at each sampling interval. All samples were immediately frozen
      (-80 degrees C) after collection and stored prior to assay. Total concentrations
      of tobramycin and ceftazidime in dialysate fluid were determined by high
      performance liquid chromatography. The last time point when tobramycin or
      ceftazidime concentration was >90% from baseline was used to denote stability.
      RESULTS: All solutions were clear in appearance and no color change or
      precipitation was observed during the study. For tobramycin, under refrigeration,
      a mean of 94.6%+/-2.3% of the initial concentration remained at 336 hours (14
      days); at room temperature, 90.5%+/-4.3% remained at 168 hours (7 days); at body
      temperature, 90.0%+/-8.1% remained at 24 hours. For ceftazidime, under
      refrigeration, a mean of 98.0%+/-0.3% of the initial concentration remained at
      168 hours (7 days); at room temperature, 91.6%+/-2.0% remained at 48 hours; at
      body temperature, 93.9%+/-1.1% remained at 8 hours. Stability was not assessed
      beyond these respective time points. CONCLUSION: Premixed tobramycin-icodextrin
      PD solution remains stable for 336 hours (14 days) when refrigerated (4 degrees
      C) and for 168 hours (7 days) at room temperature (25 degrees C). Ceftazidime
      icodextrin PD solution is stable for 168 hours and 48 hours, respectively, when
      stored at 4 degrees C and 25 degrees C. It is recommended that the bags be kept
      refrigerated whenever possible. Tobramycin-icodextrin solution stored at body
      temperature was stable up to 24 hours, and ceftazidime-icodextrin solutions up to
      8 hours, permitting the practice of pre-warming solutions prior to
      administration.

PMID- 19164254
TI  - Factors associated with sudden death in peritoneal dialysis patients.
AB  - BACKGROUND: Relatively little is known of the epidemiology and predictors of
      sudden death in peritoneal dialysis (PD) populations. We aimed to identify the
      risk factors of sudden death among PD subjects. METHODS: To explore clinical
      correlates of sudden death in PD patients, we conducted a population-based case
      control study using data from a single dialysis unit. Cases (n=24) were defined
      as all PD patients that met the criteria for sudden death during January 2003
      through December 2006. We also selected 48 control subjects that were selected
      from the prevalent PD patient name list compiled in alphabetical order. Data on
      the hemoglobin, potassium, and calcium levels, residual renal function, dialysis
      adequacy, cardiovascular risks, comorbid conditions, concurrent use of aspirin,
      beta-blockers, angiotensin-converting enzyme inhibitors, and erythropoietin,
      electrocardiographic and echocardiographic findings were extracted from case
      notes and computer records. Confounders were controlled by logistic regression.
      RESULTS: Over a period of 4 years, 24 PD patients (mean age 61.4+/-9.5 years,
      median duration of dialysis 3.1 years) experienced sudden death. Univariate
      analyses showed that patients that died suddenly were more likely to be male and
      to have diabetes mellitus, a history of smoking, and a lower small solute
      clearance as measured by Kt/V. Cases of sudden death were also more likely to
      have received blood transfusion within the previous 1 year. There were no
      significant differences between patients and controls for residual renal
      function, serum potassium levels, control of blood pressure and mineral
      metabolism, or hemoglobin levels. Multivariate regression analysis confirmed
      independent association between recent blood transfusion and increased odds of
      sudden death [adjusted odds ratio (OR) 5.18, 95% confidence interval (CI) 1.44
      18.6]. Two other factors significantly associated with risk of sudden death were
      male gender (adjusted OR 4.16, 95% CI 1.14-15.2) and diabetes mellitus (adjusted
      OR 5.33, 95% CI 1.53-18.6). CONCLUSION: This study shows that recent blood
      transfusion is associated with an increased likelihood of sudden death in PD
      patients. The mechanisms that underlie this observation are unclear.

PMID- 19164255
TI  - Subclinical peripheral artery disease in patients undergoing peritoneal dialysis:
      risk factors and outcome.
AB  - BACKGROUND: Peripheral artery disease (PAD) is highly prevalent among patients in
      end-stage renal disease. The ankle-brachial index (ABI) is believed to be highly
      correlated with the subclinical PAD of lower extremities but little is known
      about the associated risk factors and outcome for PAD and ABI in patients on
      peritoneal dialysis (PD). METHODS: We performed a cohort study of 153 patients
      from a single center receiving stable PD for more than 3 months. These patients
      were screened for subclinical PAD using the ABI measurement. The ABI was measured
      and a ratio of <0.9 was considered abnormal. Clinical outcomes included actuarial
      patient and technique survival in this study. RESULTS: 30 patients were
      classified into a subclinical PAD group. The prevalence of PAD (subclinical and
      overt) in our PD center was 19.61% (30/153). Advanced age, preexisting diabetes,
      preexisting cardiovascular and/or cerebrovascular disease (CVD), lower renal Kt/V
      urea, lower renal creatinine clearance (WCrCl), lower serum albumin level, and
      higher serum triglyceride level were risk factors for PAD in our PD center.
      Bivariate analysis showed that ABI was positively correlated with residual renal
      Kt/V urea and WCrCl, but was not correlated with peritoneal Kt/V urea and WCrCl.
      Patient and technique survival rates were significantly lower in the low ABI
      group than in the normal ABI group. CONCLUSIONS: ABI is highly correlated with
      advanced age, preexisting diabetes, preexisting CVD, serum albumin, serum
      triglyceride, and residual renal clearance in PD patients. Also, lower ABI is
      independently associated with a high risk of patient mortality and PD technique
      failure.

PMID- 19164256
TI  - Kinetic analysis of peritoneal fluid and solute transport with combination of
      glucose and icodextrin as osmotic agents.
AB  - BACKGROUND: Controlling extracellular volume and plasma sodium concentration are
      two crucial objectives of dialysis therapy, as inadequate sodium and fluid
      removal by dialysis may result in extracellular volume overload, hypertension,
      and increased cardiovascular morbidity and mortality in end-stage renal disease
      patients. A new concept to enhance sodium and fluid removal during peritoneal
      dialysis (PD) is the use of dialysis solutions with two different osmotic agents.
      AIM: To investigate and compare, with the help of mathematical modeling and
      computer simulations, fluid and solute transport during PD with conventional
      dialysis fluids (3.86% glucose and 7.5% icodextrin; both with standard sodium
      concentration) and a new combination fluid with both icodextrin and glucose (CIG;
      2.6% glucose/6.8% icodextrin; low sodium concentration). In particular, this
      paper is devoted to improving mathematical modeling based on critical appraisal
      of the ability of the original three-pore model to reproduce clinical data and
      check its validity across different types of osmotic agents. METHODS: Theoretical
      investigations of possible causes of the improved fluid and sodium removal during
      PD with the combination solution (CIG) were carried out using the three-pore
      model. The results of computer simulations were compared with clinical data from
      dwell studies in 7 PD patients. To fit the model to the low net ultrafiltration
      (366+/-234 mL) obtained after a 4-hour dwell with 3.86% glucose, some of the
      original parameters proposed in the three-pore model (Rippe & Levin. Kidney Int
      2000; 57:2546-56) had to be modified. In particular, the aquaporin-mediated
      fractional contribution to hydraulic permeability was decreased by 25% and small
      pore radius increased by 18%. RESULTS: The simulations described well clinical
      data that showed a dramatic increase in ultrafiltration and sodium removal with
      the CIG fluid in comparison with the two other dialysis fluids. However, to adapt
      the three-pore model to the selected group of PD patients (fast transporters with
      small ultrafiltration capacity on average), the peritoneal pore structure had to
      be modified. As the mathematical model was capable of reproducing the clinical
      data, this shows that the enhanced ultrafiltration with the combination fluid is
      caused by the additive effect of the two different osmotic agents and not by a
      specific impact of the new dialysis fluid on the transport characteristics of the
      peritoneum.

PMID- 19164257
TI  - Effects of interleukin-6 T15A single nucleotide polymorphism on baseline
      peritoneal solute transport rate in incident peritoneal dialysis patients.
AB  - OBJECTIVE: To study the genetic effects of various inflammatory cytokines on
      peritoneal solute transport rate (PSTR) in incident Korean peritoneal dialysis
      (PD) patients. DESIGN: Case-control association study. METHODS: 132 patients with
      baseline peritoneal equilibration test within 1-3 months after starting PD were
      enrolled. We analyzed the influence of single nucleotide polymorphisms (SNPs) of
      interleukin-6 (IL-6; -572G/C, T15A), tumor necrosis factor-alpha (TNF-alpha; 
      1031C/T, -863C/A, -308G/A), and IL-10 (-1082A/G, -592A/C) on baseline PSTR.
      Clinical parameters such as age, gender, presence of diabetes mellitus,
      comorbidity, C-reactive protein, and residual renal function were also included
      as covariates. RESULTS: The T15A SNP of IL-6 (rs13306435) was associated with
      PSTR. Patients with TA genotype (n=18) had significantly lower D4/P creatinine
      (0.65+/-0.087 vs 0.73+/-0.110, p=0.0046) and higher D4/D0 glucose (0.39+/-0.174
      vs 0.31+/-0.119, p=0.027) than patients with TT genotype (n=114). The log value
      of the dialysate appearance rate of IL-6 had a strong positive correlation with
      D4/P creatinine (r2=0.1294, p<0.0001) and was significantly lower in the TA
      genotype than the TT genotype (201.7+/-14.42 vs 116.8+/-88.91 pg/minute,
      p=0.0358). By multiple logistic regression, TA genotype was negatively associated
      with a higher PSTR (high or high average; odds ratio 0.18; 95% confidence
      interval 0.048-0.666). CONCLUSIONS: In incident Korean PD patients, T15A
      polymorphism of IL-6 is associated with dialysate IL-6 concentration and baseline
      PSTR.

PMID- 19164258
TI  - Antioxidant status of patients on peritoneal dialysis: associations with
      inflammation and glycoxidative stress.
AB  - BACKGROUND: Patients on peritoneal dialysis (PD) frequently exhibit oxidant
      antioxidant imbalance, advanced glycation end-product overload, and subclinical
      inflammation but the interrelations between these pathophysiological changes have
      not been fully elucidated. SUBJECTS AND METHODS: To study possible associations,
      a cross-sectional study of antioxidant status, glycoxidative stress, and
      inflammation, using HPLC and ELISA methods, was undertaken in 37 PD patients and
      age- and sex-matched healthy controls. RESULTS: Plasma ascorbate concentrations
      were low in patients not taking at least low-dose vitamin C supplements. In
      patients taking vitamin C supplements, there was a positive relation between
      ascorbate and pentosidine concentrations. Vitamin E and carotenoid concentrations
      were comparable between patients and controls, while lycopene and
      lutein/zeaxanthin concentrations were lower. Interleukin-6, C-reactive protein
      (CRP), and pentosidine concentrations were elevated in PD patients. beta
      Cryptoxanthin, lycopene, and lutein/zeaxanthin concentrations were inversely
      related to interleukin-6 concentrations. beta-Cryptoxanthin concentrations were
      also inversely related to CRP concentrations. Pentosidine showed a low dialysate
      to-plasma ratio, indicating low peritoneal clearance. Pentosidine concentrations
      increased with duration of PD therapy, while alpha- and beta-carotene
      concentrations decreased. Malondialdehyde concentrations were elevated compared
      to controls but remained within the normal range. Retinol concentrations
      decreased with PD therapy and were inversely related to interleukin-6 and CRP
      concentrations. CONCLUSIONS: Low-dose vitamin C supplements and a carotenoid-rich
      diet should be recommended for PD patients to maintain normal antioxidant status
      and efficiently counteract the chronic inflammatory response, rather than high
      doses of vitamin C, which could play a role as a precursor of pentosidine.

PMID- 19164259
TI  - Polyneuropathy in diabetic and nondiabetic patients on CAPD: is there an
      association with HRQOL?
AB  - BACKGROUND: It is well known that patients with uremia, as well as patients with
      diabetes mellitus, develop polyneuropathy. OBJECTIVES: The signs of
      polyneuropathy in diabetic and nondiabetic patients on continuous ambulatory
      peritoneal dialysis (CAPD) and their relation with age, duration of dialysis,
      biochemical parameters, dialysis adequacy, and health-related quality of life
      (HRQOL) were analyzed in the present study. PATIENTS AND METHODS: 65 CAPD
      patients (37 men, age 29-85 years, duration on dialysis 3 months to 14 years)
      were divided into two groups: group 1 was comprised of 20 diabetic patients (mean
      age 50.1+/-13.2 years); group 2 was comprised of 45 nondiabetic patients (mean
      age 62.3+/-9.7 years). Biochemical parameters, dialysis adequacy, and clinical
      signs were determined. Motor conduction velocity on the peroneal and tibial
      nerves and sensitive conduction velocity on the sural nerve were measured. The
      Kidney Disease Quality of Life Short Form (KDQOL-SF) was used to measure the CAPD
      patients' self-assessment of functioning and well-being using 4 component scores:
      physical component summary (PCS), mental component summary (MCS), kidney disease
      target issues, and patient satisfaction. RESULTS: Subjective symptoms were more
      intense in the diabetic patients and correlated with changes in peroneal and
      tibial distal motor latency (DML). Diabetic patients were significantly younger,
      had lower creatinine and higher glucose levels, and all analyzed pathological
      neurophysiological parameters were higher. Nondiabetic patients had prolonged
      latency of the F-wave on the peroneal nerve and the tibial nerve and reduced
      sensitive conduction velocity on the sural nerve. Significant correlations were
      found between the analyzed neurophysiological parameters and duration of dialysis
      and diabetes, glucose concentration, and dialysis adequacy in diabetic patients,
      and between neurophysiological parameters and age and dialysis adequacy in
      nondiabetic patients. Analysis of the 4 component scores of the KDQOL-SF revealed
      that diabetic patients had significantly better scores for PCS and MCS, which can
      be explained by their younger age. Patient satisfaction was worse in diabetic
      patients and correlated with duration of diabetes. In addition, significant
      correlations were established between PCS, MCS, and tibial DML (late neuropathic
      changes) in diabetic patients, and between MCS and tibial F-wave (early
      neuropathic changes) in nondiabetic patients. CONCLUSION: Polyneuropathy was
      significantly worse in diabetic than in nondiabetic patients on CAPD. DML on the
      tibial nerve correlated with glucose concentration, dialysis adequacy, PCS, and
      MCS in diabetic patients, whereas in nondiabetic patients, dialysis adequacy and
      azotemia correlated with F-waves on the peroneal nerve and the tibial nerve but
      MCS only with F-wave on the tibial nerve.

PMID- 19164260
TI  - Effect of short-term rosiglitazone therapy in peritoneal dialysis patients.

PMID- 19164261
TI  - Direct measurement of nitric oxide concentration in CAPD dialysate.

PMID- 19164262
TI  - CAPD: developments during changing times.

PMID- 19164263
TI  - Efficacy of peritoneal dialysis with icodextrin in the long-term treatment of
      refractory congestive heart failure.

PMID- 19164264
TI  - Another peritoneal dialysis catheter encapsulated in peritoneal tissue.

PMID- 19164265
TI  - An unusual cause of skin ulceration in a very long-term peritoneal dialysis
      patient.

PMID- 19164268
TI  - Everything old is new again.

PMID- 19164269
TI  - Effects of exercise and caloric restriction on insulin resistance and
      cardiometabolic risk factors in older obese adults--a randomized clinical trial.
AB  - BACKGROUND: The prevalence of insulin resistance, metabolic syndrome, and
      cardiovascular disease is greatest in older obese patients, and effective
      evidence-based treatment strategies are lacking. METHODS: A prospective
      controlled study was conducted on 24 older (65.5 +/- 5.0 years) obese (body mass
      index, 34.3 +/- 5.2 kg/m(2)) adults with clinically diagnosed metabolic syndrome.
      We examined the effect of exercise alone (EX) or exercise combined with moderate
      caloric restriction (-500 kcal, EX + CR) on metabolic and cardiovascular risk
      factors. Measures of insulin sensitivity assessed by euglycemic hyperinsulinemic
      clamp and by oral glucose tolerance test, lipid profiles, blood pressure, body
      composition, abdominal fat, and aerobic capacity were all obtained before and
      after the interventions. RESULTS: Both groups experienced significant weight
      loss, but the reduction was greater in the EX + CR group than in the EX group (
      6.8 +/- 2.7 kg vs -3.7 +/- 3.4 kg, respectively, p = .02). Both interventions
      improved insulin sensitivity (2.4 +/- 2.4 mg/kg FFM/min and 1.4 +/- 1.7
      mg/kgFFM/min, respectively, p < .001) and indices of metabolic syndrome
      (systolic/diastolic blood pressure, waist circumference, glucose, and
      triglycerides; p < .05). High-density lipoprotein levels remained unchanged.
      Total abdominal, subcutaneous, and visceral fat; aerobic capacity; and total and
      low-density lipoprotein cholesterol were also improved. With the exception of
      weight loss and subcutaneous fat, there was no difference in the magnitude of
      improvement between the interventions. CONCLUSION: These data suggest that
      exercise alone is an effective nonpharmacological treatment strategy for insulin
      resistance, metabolic syndrome, and cardiovascular disease risk factors in older
      obese adults.

PMID- 19164270
TI  - Long-term effect of physical activity counseling on mobility limitation among
      older people: a randomized controlled study.
AB  - BACKGROUND: Physical activity counseling increases physical activity among older
      people, but its effectiveness on mobility, that is, maintaining the ability to
      move independently, is unknown. We studied the effect of physical activity
      counseling on mobility among older people and evaluated whether counseling
      induced benefits persist after cessation of the intervention. METHODS: In a 2
      year, single-blinded, randomized controlled study, 632 sedentary participants
      aged 75-81 years were randomly assigned into the intervention (n = 318) or
      control (n = 314) group. The intervention group received a single individualized
      physical activity counseling session with a supportive telephone contact every 4
      months for 2 years. The outcome measures-perceived difficulty in advanced
      (walking 2 km) and basic (walking 0.5 km) mobility-were gathered semiannually
      during the intervention and the 1.5-year postintervention follow-up. RESULTS: The
      proportion of participants with difficulties in advanced mobility at the
      beginning and end of the intervention was 34% and 38%, respectively, in the
      intervention group. In the control group, the corresponding proportions were 32%
      and 45%. The treatment effect was significant at the 2-year follow-up (odds ratio
      [OR] 0.84, 95% confidence interval [CI]: 0.70-0.99; p = .04) and remained
      significant 1.5 years postintervention (OR 0.82, 95% CI: 0.68-0.99; p = .04). The
      effect on basic mobility postintervention was parallel but nonsignificant (OR
      0.87, CI: 0.69-1.09; p = .22). CONCLUSIONS: Among older people, a single
      individualized physical activity counseling session with a supportive phone
      contact every 4 months for 2 years had a positive effect on mobility, an
      important factor for maintaining independence in the community in old age.

PMID- 19164271
TI  - The emerging threat of multidrug-resistant gram-negative organisms in long-term
      care facilities.
AB  - BACKGROUND: Infections caused by antimicrobial-resistant bacteria are associated
      with substantial morbidity and mortality. Residents of long-term care facilities
      (LTCF) are among the main reservoirs of antimicrobial-resistant bacteria,
      including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin
      resistant enterococci (VRE). Multidrug-resistant gram-negative organisms (MDRGN)
      are emerging as important pathogens among LTCF residents. Data on the clinical
      epidemiology of MDRGN, especially in comparison to VRE and MRSA, are limited.
      METHODS: All clinical cultures collected from residents of a 750-bed LTCF for a
      period of 2 years were analyzed for the presence of MDRGN, VRE, and MRSA.
      Multidrug resistance among gram-negative bacteria was defined as resistance to
      three or more antimicrobials or antimicrobial groups including extended-spectrum
      penicillins (ampicillin/sulbactam or piperacillin/tazobactam), cephalosporins
      (cefazolin or ceftriaxone), gentamicin, ciprofloxacin, and trimethoprim
      sulfamethoxazole (TMP/SMX). RESULTS: A total of 1,661 clinical cultures were
      included in the analysis. MDRGN were recovered from 180 (10.8%) cultures, MRSA
      from 104 (6.3%), and VRE from 11 (0.6%). MDRGN were isolated more frequently than
      MRSA or VRE throughout the study period. The prevalence of MDRGN increased
      significantly from 7% in 2003 to 13% in 2005 (p = .001). More than 80% of MDRGN
      isolates were resistant to ciprofloxacin, TMP/SMX, and ampicillin/sulbactam.
      Resistance to three, four, and five or more antimicrobials were identified among
      122 (67.8%), 47 (26.1%), and 11 (6.1%) MDRGN isolates, respectively. CONCLUSIONS:
      Rates of MDRGN exceeded those of MRSA and VRE and increased throughout the study
      period. Resistance to multiple, commonly prescribed antimicrobials among MDRGN
      raises concerns about therapeutic options available to treat MDRGN infections
      among LTCF residents.

PMID- 19164272
TI  - Correlates of self-reported nocturia among community-dwelling older adults.
AB  - BACKGROUND: Nocturia is a common and bothersome problem with multifactorial
      etiology. This study examines clinical factors that are associated with nocturia
      among community-dwelling older adults. METHODS: A questionnaire-based survey was
      conducted among a convenience sample of community-dwelling older adults. Nocturia
      was defined as waking up to urinate two or more times per night for 3 or more
      days per week. Associations between nocturia status and sleep disturbance,
      daytime sleepiness, disease burden, and history of falls were determined.
      RESULTS: Questionnaires were mailed out to 433 participants, and returned
      questionnaires from 247 individuals (58%) individuals were adequate for analysis.
      There were 144 women (57%) and 103 men (42%), with mean +/- standard deviation
      age of 75.1 +/- 6.9 and 76.6 +/- 5.6 years for women and men, respectively. A
      total of 137 participants (55%) endorsed nocturia, and 57 participants (23%)
      endorsed nocturia and difficulty going back to sleep. Participants who endorsed
      nocturia and difficulty going back to sleep were more likely to report poor sleep
      quality, daytime sleepiness, increased disease burden, one or more falls, and
      symptoms related to primary sleep disorders. CONCLUSIONS: The clinical
      characteristics of study participants with nocturia and difficulty going back to
      sleep were different from those with nocturia and no difficulty going back to
      sleep, suggesting that these two conditions may have different etiological
      factors and clinical consequences. These findings would have important
      implications in both clinical and research-related activities aimed at the
      management of nocturia in older adults.

PMID- 19164273
TI  - Association of low vitamin D levels with the frailty syndrome in men and women.
AB  - BACKGROUND: Although both vitamin D (25-hydroxyvitamin D [25(OH)D]) insufficiency
      and the frailty syndrome are more prevalent in women than men, sex-specific
      associations have not been explored. We estimated sex-specific associations of
      low 25(OH)D with frailty. Vitamin D insufficiency can result in
      hyperparathyroidism, and thus, parathyroid hormone (PTH) was explored as a
      potential mediator in the relationship between 25(OH)D levels and frailty.
      METHODS: The sample included 444 male and 561 female participants aged 65 years
      and older from the InCHIANTI study for whom 25(OH)D levels and frailty
      information were available. Frailty was defined as the presence of at least three
      of the five following criteria: slowness, weakness, low energy expenditure,
      exhaustion, and weight loss. Logistic regression models estimated the association
      between serum levels of 25(OH)D and PTH with frailty, controlling for potential
      confounders. RESULTS: Independent of covariates, men with 25(OH)D <50 nmol/L had
      greater odds of frailty than those with 25(OH)D > or =50 nmol/L (odds ratio [OR]
      = 4.94, 95% confidence interval [CI] = 1.80-13.61). In women, the adjusted OR for
      frailty (95% CI) was 1.43 (0.58-3.56). The 25(OH)D ORs differed between men and
      women (p = .041). ORs changed little after controlling for PTH. However, when low
      energy expenditure was excluded from the frailty definition, adjusted OR for
      frailty in men (95% CI) was 2.18 (0.59-8.04); controlling for PTH attenuated this
      OR by 32%. In women, the OR (95% CI) for frailty (low energy expenditure
      excluded) was 1.54 (0.31-7.58) and was attenuated by 6% after controlling for
      PTH. CONCLUSIONS: Vitamin D insufficiency was associated with frailty in men, but
      not in women. Results suggest that PTH mediates the relationship between 25(OH)D
      and nonenergy expenditure aspects of frailty.

PMID- 19164274
TI  - Metabolic syndrome and physical decline in older persons: results from the
      Health, Aging And Body Composition Study.
AB  - BACKGROUND: The metabolic syndrome includes dyslipidemia, abdominal obesity,
      insulin resistance, and hypertension and is associated with an increased risk of
      diabetes and cerebrovascular disease (CVD), but consequences beyond these
      outcomes have not been examined extensively. We investigated whether metabolic
      abnormalities have independent consequences on loss of mobility function of older
      persons. METHODS: Data are from 2,920 men and women, 70-79 years, participating
      in the Health ABC study without mobility limitations at baseline. Metabolic
      syndrome was defined as > or =3 of the following: (a) waist circumference >102
      (men) or >88 cm (women); (b) triglycerides > or =150 mg/dL; (c) high-density
      lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women); (d) blood pressure
      > or =130/85 mm Hg or antihypertensive medication; and (d) fasting glucose > or
      =110 mg/dL or antidiabetic medication. Mobility limitation was defined as
      difficulty or inability walking (1/4) mile or climbing 10 steps during two
      consecutive semiannual assessments over 4.5 years. RESULTS: The prevalence of
      metabolic syndrome was 38.6%. The metabolic syndrome was associated with an
      adjusted relative risk (RR) of 1.46 (95% confidence interval [CI] = 1.30-1.63)
      for developing mobility limitations. The risk increased when more metabolic
      syndrome components were present (p trend >.001). All metabolic syndrome
      components were significantly associated with incident mobility limitations with
      the highest RRs for abdominal obesity (RR = 1.54, 95% CI = 1.35-1.75) and
      hyperglycemia (RR = 1.44, 95% CI = 1.27-1.63). Findings were unchanged when
      persons with baseline, or incident, CVD, stroke, or diabetes were excluded.
      CONCLUSIONS: Metabolic syndrome abnormalities, especially abdominal obesity and
      hyperglycemia, are predictive of mobility limitations in the elderly, independent
      of CVD or diabetes.

PMID- 19164275
TI  - Single and combined effects of cerebral white matter lesions and lacunar
      infarctions on cognitive function in an elderly population.
AB  - BACKGROUND: This study is to investigate the association between single and
      combined vascular brain changes (white matter lesions [WMLs], lacunar
      infarctions) and the cognitive domains of memory, processing speed, and motor
      function in the elderly adults. METHODS: In a sample of 268 participants aged 65
      83 years of the MEMO (Memory and Morbidity in Augsburg Elderly) population-based
      study in Augsburg, Germany, cerebral magnetic resonance imaging (MRI) was
      performed and a detailed neuropsychological test battery applied. Analysis of
      covariance determined the effects of vascular brain changes on domains of
      cognitive functioning. RESULTS: Strong associations of large WMLs and of MRI
      defined lacunar infarction with three different domains of cognitive function
      even after adjustment for age, gender, and education were found. The combined
      occurrence of both lesions affected about one in 10 participants and was
      associated with a strong decrease in cognitive function in all domains. The
      difference between the groups with only one lesion type (either large WMLs or MRI
      defined infarction) and participants affected by both was significant in the
      domains of processing speed and memory, even after adjustment for important
      confounders such as age, gender, education, and comorbidities. The effects of
      both lesion types on cognitive function were not more than additive. CONCLUSIONS:
      Our study shows that both large WMLs and MRI-defined lacunar infarction
      contribute to impairments in different cognitive domains. The results suggest
      that their combined occurrence is associated with stronger reductions in
      cognitive function than each of the two brain lesion types alone.

PMID- 19164276
TI  - Physical activity as a preventative factor for frailty: the health, aging, and
      body composition study.
AB  - BACKGROUND: It is unclear if physical activity (PA) can prevent or reverse
      frailty. We examined different doses and types of PA and their association with
      the onset and severity of frailty. METHODS: Health, Aging and Body Composition
      (Health ABC) study participants (N = 2,964) were followed for 5 years, with
      frailty defined as a gait speed of less than 0.60 m/s and/or inability to rise
      from a chair without using one's arms. Individuals with one impairment were
      considered moderately frail and those with both severely frail. We examined PA
      doses of volume and intensity, activity types (eg, lifestyle vs exercise
      activities), and their associations with incident frailty and transition to
      severe frailty in those who became frail. RESULTS: Adjusted models indicated that
      sedentary individuals had significantly increased odds of developing frailty
      compared with the exercise active group (adjusted odds ratio [OR] = 1.45; 95%
      confidence interval [CI]: 1.04-2.01), whereas the lifestyle active did not.
      Number of diagnoses was the strongest predictor of incident frailty. In those who
      became frail during follow-up (n = 410), there was evidence that the sedentary
      (adjusted OR = 2.80; 95% CI: 0.98-8.02) and lifestyle active (adjusted OR = 2.81;
      95% CI: 1.22-6.43) groups were more likely to have worsening frailty over time.
      CONCLUSIONS: Despite the strong relationship seen between comorbid conditions and
      onset of frailty, this observational study suggests that participation in self
      selected exercise activities is independently associated with delaying the onset
      and the progression of frailty. Regular exercise should be further examined as a
      potential factor in frailty prevention for older adults.

PMID- 19164277
TI  - Discovering new bioactive neuropeptides in the striatum secretome using in vivo
      microdialysis and versatile proteomics.
AB  - The striatum, a major component of the brain basal nuclei, is central for
      planning and executing voluntary movements and undergoes lesions in
      neurodegenerative disorders such as Huntington disease. To perform highly
      integrated tasks, the striatum relies on a complex network of communication
      within and between brain regions with a key role devoted to secreted molecules.
      To characterize the rat striatum secretome, we combined in vivo microdialysis
      together with proteomics analysis of trypsin digests and peptidomics studies of
      native fragments. This versatile approach, carried out using different
      microdialysis probes and mass spectrometer devices, allowed evidencing with high
      confidence the expression of 88 proteins and 100 processed peptides. Their
      secretory pathways were predicted by in silico analysis. Whereas high molecular
      weight proteins were mainly secreted by the classical mode (94%), low molecular
      weight proteins equally used classical and non-classical modes (53 and 47%,
      respectively). In addition, our results suggested alternative secretion
      mechanisms not predicted by bioinformatics tools. Based on spectrum counting, we
      performed a relative quantification of secreted proteins and peptides in both
      basal and neuronal depolarization conditions. This allowed detecting a series of
      neuropeptide precursors and a 6-fold increase for neurosecretory protein VGF and
      proenkephalin (PENK) levels. A focused investigation and a long peptide
      experiment led to the identification of new secreted non-opioid PENK peptides,
      referred to as PENK 114-133, PENK 239-260, and PENK 143-185. Moreover we showed
      that injecting synthetic PENK 114-133 and PENK 239-260 into the striatum robustly
      increased glutamate release in this region. Thus, the combination of
      microdialysis and versatile proteomics methods shed new light on the secreted
      protein repertoire and evidenced novel neuropeptide transmitters.

PMID- 19164278
TI  - Identification of early intestinal neoplasia protein biomarkers using laser
      capture microdissection and MALDI MS.
AB  - Obtaining protein profiles from a homogeneous cell population in tissues can
      significantly improve our capability in protein biomarker discovery. In this
      study, unique protein profiles from the top and bottom sections of mouse crypts
      and Apc(Min+/-) adenomas were obtained using laser capture microdissection (LCM)
      combined with MALDI MS. Statistically significant protein peaks with differential
      expression were selected, and a set of novel protein biomarkers were identified.
      Immunohistochemistry was performed to confirm the differentially expressed
      protein biomarkers found by LCM combined with MALDI MS. To validate the relevance
      of the findings in human colorectal cancer (CRC), S100A8 was further confirmed in
      human CRC using immunohistochemistry. In addition, S100A8 was found to have an
      increased expression at different human CRC stages (Duke's A-D) compared with
      controls at both protein (n = 168 cases) and RNA (n = 215 cases) levels. Overall
      LCM combined with MALDI MS is a promising method to identify intestinal protein
      biomarkers from minute amounts of tissue. The novel protein biomarkers identified
      from the top and bottom crypts will increase our knowledge of the specific
      protein changes taking place during cell migration from the crypt bottom to top.
      In addition, the identified cancer protein biomarkers will aid in the exploration
      of colorectal tumorigenesis mechanisms as well as in the advancement of
      molecularly based diagnosis of colorectal cancer.

PMID- 19164279
TI  - Grade-dependent proteomics characterization of kidney cancer.
AB  - Kidney cancer is frequently metastatic on presentation at which point the disease
      is associated with a 95% mortality. Assessment of tumor grade on pathological
      examination is the most powerful means for prognostication as well as for
      stratification of patients into those who might respond to conventional or
      targeted therapy. Although there exist several grading systems in common use, all
      suffer from significant disparity among observers. In an attempt to objectify
      this process as well as to acquire grade-specific mechanistic information, we
      performed LC-MS/MS-based proteomics analysis on 50 clear cell kidney cancers
      equally distributed among normal tissues and Fuhrman grades 1-4. Initial
      experiments confirmed the utility of using archived formalin-fixed paraffin
      embedded samples for LC-MS/MS-based proteomics analysis, and the LC-MS/MS
      findings were validated by extensive immunoblotting. We now show that changes
      among many biochemical processes and pathways are strongly grade-dependent with
      the glycolytic and amino acid synthetic pathways highly represented. In addition,
      proteins relating to acute phase and xenobiotic metabolism signaling are highly
      represented. Self-organized mapping of proteins with similar patterns of
      expression led to the creation of a heat map that will be useful in grade
      characterization as well as in future research relating to oncogenic mechanisms
      and targeted therapies for kidney cancer.

PMID- 19164280
TI  - Protein ionizable groups: pK values and their contribution to protein stability
      and solubility.
AB  - The structure, stability, solubility, and function of proteins depend on their
      net charge and on the ionization state of the individual residues. Consequently,
      biochemists are interested in the pK values of the ionizable groups in proteins
      and how these pK values depend on their environment. We review what has been
      learned about pK values of ionizable groups in proteins from experimental studies
      and discuss the important contributions they make to protein stability and
      solubility.

PMID- 19164281
TI  - The effects of amyloid precursor protein on postsynaptic composition and
      activity.
AB  - The amyloid precursor protein (APP) is cleaved to produce the Alzheimer disease
      associated peptide Abeta, but the normal functions of uncleaved APP in the brain
      are unknown. We found that APP was present in the postsynaptic density of central
      excitatory synapses and coimmunoprecipitated with N-methyl-d-aspartate receptors
      (NMDARs). The presence of APP in the postsynaptic density was supported by the
      observation that NMDARs regulated trafficking and processing of APP;
      overexpression of the NR1 subunit increased surface levels of APP, whereas
      activation of NMDARs decreased surface APP and promoted production of Abeta. We
      transfected APP or APP RNA interference into primary neurons and used
      electrophysiological techniques to explore the effects of APP on postsynaptic
      function. Reduction of APP decreased (and overexpression of APP increased) NMDAR
      whole cell current density and peak amplitude of spontaneous miniature excitatory
      postsynaptic currents. The increase in NMDAR current by APP was due to specific
      recruitment of additional NR2B-containing receptors. Consistent with these
      findings, immunohistochemical experiments demonstrated that APP increased the
      surface levels and decreased internalization of NR2B subunits. These results
      demonstrate a novel physiological role of postsynaptic APP in enhancing NMDAR
      function.

PMID- 19164282
TI  - The filament-specific Rep1-1 repellent of the phytopathogen Ustilago maydis forms
      functional surface-active amyloid-like fibrils.
AB  - Repellents of the maize pathogen Ustilago maydis are involved in formation of
      hydrophobic aerial hyphae and in cellular attachment. These peptides, called Rep1
      1 to Rep1-11, are encoded by the rep1 gene and result from cleavage of the
      precursor protein Rep1 during passage of the secretion pathway. Using green
      fluorescent protein as a reporter, we here show that rep1 is expressed in
      filaments and not in the yeast form of U. maydis. In situ hybridization localized
      rep1 mRNA in the apex of the filament, which correlates with the expected site of
      secretion of the repellents into the cell wall. We also produced a synthetic
      peptide, Rep1-1. This peptide reduced the water surface tension to as low as 36
      mJ m(-2). In addition, it formed amyloid-like fibrils as was shown by negative
      staining, by thioflavin T fluorescence, and by x-ray diffraction. These fibrils
      were not soluble in SDS but could be dissociated with trifluoroacetic acid. The
      repellents in the hyphal cell wall had a similar solubility and also stained with
      thioflavin T, strongly indicating that they are present as amyloid fibrils.
      However, such fibrils could not be observed at the hyphal surface. This can be
      explained by the fact that the Rep1-1 filaments decrease in length at increasing
      concentrations. Taken together, we have identified the second class of fungal
      proteins that form functional amyloid-like filaments at the hyphal surface.

PMID- 19164283
TI  - Sp1 and AP-1 regulate expression of the human gene VIL2 in esophageal carcinoma
      cells.
AB  - Ezrin, encoded by VIL2, is a membrane-cytoskeletal linker protein that has been
      suggested to be involved in tumorigenesis. Ezrin expression in esophageal
      squamous cell carcinoma (ESCC) was described recently, but its clinical
      significance and the molecular mechanism underlying its regulated expression
      remain unclear. Thus, we retrospectively evaluated ezrin expression by
      immunohistochemistry in a tissue microarray representing 193 ESCCs. Ezrin
      overexpression in 90 of 193 tumors (46.6%) was associated with poor survival (p =
      0.048). We then explored the mechanism by which ezrin expression is controlled in
      ESCC by assessing the transcriptional regulatory regions of human VIL2 by fusing
      deletions or site-directed mutants of the 5'-flanking region of the gene to a
      luciferase reporter. We found that the region -87/-32 containing consensus Sp1 (
      75/-69) and AP-1 (-64/-58) binding sites is crucial for VIL2 promoter activity in
      esophageal carcinoma cells (EC109) derived from ESCC. AP-1 is comprised of c-Jun
      and c-Fos. Electrophoretic mobility shift and chromatin immunoprecipitation
      experiments demonstrated that Sp1 and c-Jun bound specifically to their
      respective binding sites within the VIL2 promoter. In addition, transient
      expression of Sp1, c-Jun, or c-Fos increased ezrin expression and VIL2 promoter
      activity. Use of selective inhibitors revealed that VIL2 transactivation required
      the MEK1/2 signal transduction pathway but not JNK or p38 MAPK. Taken together,
      we propose a possible signal transduction pathway whereby MEK1/2 phosphorylates
      ERK1/2, which phosphorylates Sp1 and AP-1 that in turn bind to their respective
      binding sites to regulate the expression of human VIL2 in ESCC cells.

PMID- 19164284
TI  - A novel role for embigin to promote sprouting of motor nerve terminals at the
      neuromuscular junction.
AB  - Adult skeletal muscle accepts ectopic innervation by foreign motor axons only
      after section of its own nerve, suggesting that the formation of new
      neuromuscular junctions is promoted by muscle denervation. With the aim to
      identify new proteins involved in neuromuscular junction formation we performed
      an mRNA differential display on innervated versus denervated adult rat muscles.
      We identified transcripts encoding embigin, a transmembrane protein of the
      immunoglobulin superfamily (IgSF) class of cell adhesion molecules to be strongly
      regulated by the state of innervation. In innervated muscle it is preferentially
      localized to neuromuscular junctions. Forced overexpression in innervated muscle
      of a full-length embigin transgene, but not of an embigin fragment lacking the
      intracellular domain, promotes nerve terminal sprouting and the formation of
      additional acetylcholine receptor clusters at synaptic sites without affecting
      terminal Schwann cell number or morphology, and it delays the retraction of
      terminal sprouts following re-innervation of denervated endplates. Conversely,
      knockdown of embigin by RNA interference in wild-type muscle accelerates terminal
      sprout retraction, both by itself and synergistically with deletion of neural
      cell adhesion molecule. These findings indicate that embigin enhances neural cell
      adhesion molecule-dependent neuromuscular adhesion and thereby modulates
      neuromuscular junction formation and plasticity.

PMID- 19164285
TI  - Expression of TDP-43 C-terminal Fragments in Vitro Recapitulates Pathological
      Features of TDP-43 Proteinopathies.
AB  - The disease protein in frontotemporal lobar degeneration with ubiquitin-positive
      inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS) was identified
      recently as the TDP-43 (TAR DNA-binding protein 43), thereby providing a
      molecular link between these two disorders. In FTLD-U and ALS, TDP-43 is
      redistributed from its normal nuclear localization to form cytoplasmic insoluble
      aggregates. Moreover, pathological TDP-43 is abnormally ubiquitinated,
      hyperphosphorylated, and N-terminally cleaved to generate C-terminal fragments
      (CTFs). However, the specific cleavage site(s) and the biochemical properties as
      well as the functional consequences of pathological TDP-43 CTFs remained unknown.
      Here we have identified the specific cleavage site, Arg(208), of a pathological
      TDP-43 CTF purified from FTLD-U brains and show that the expression of this and
      other TDP-43 CTFs in cultured cells recapitulates key features of TDP-43
      proteinopathy. These include the formation of cytoplasmic aggregates that are
      ubiquitinated and abnormally phosphorylated at sites found in FTLD-U and ALS
      brain and spinal cord samples. Furthermore, we observed splicing abnormalities in
      a cell culture system expressing TDP-43 CTFs, and this is significant because the
      regulation of exon splicing is a known function of TDP-43. Thus, our results show
      that TDP-43 CTF expression recapitulates key biochemical features of pathological
      TDP-43 and support the hypothesis that the generation of TDP-43 CTFs is an
      important step in the pathogenesis of FTLD-U and ALS.

PMID- 19164286
TI  - Dissecting the mechanisms of tissue transglutaminase-induced cross-linking of
      alpha-synuclein: implications for the pathogenesis of Parkinson disease.
AB  - Tissue transglutaminase (tTG) has been implicated in the pathogenesis of
      Parkinson disease (PD). However, exactly how tTG modulates the structural and
      functional properties of alpha-synuclein (alpha-syn) and contributes to the
      pathogenesis of PD remains unknown. Using site-directed mutagenesis combined with
      detailed biophysical and mass spectrometry analyses, we sought to identify the
      exact residues involved in tTG-catalyzed cross-linking of wild-type alpha-syn and
      alpha-syn mutants associated with PD. To better understand the structural
      consequences of each cross-linking reaction, we determined the effect of tTG
      catalyzed cross-linking on the oligomerization, fibrillization, and membrane
      binding of alpha-syn in vitro. Our findings show that tTG-catalyzed cross-linking
      of monomeric alpha-syn involves multiple cross-links (specifically 2-3). We
      subjected tTG-catalyzed cross-linked monomeric alpha-syn composed of either wild
      type or Gln --> Asn mutants to sequential proteolysis by multiple enzymes and
      peptide mapping by mass spectrometry. Using this approach, we identified the
      glutamine and lysine residues involved in tTG-catalyzed intramolecular cross
      linking of alpha-syn. These studies demonstrate for the first time that Gln(79)
      and Gln(109) serve as the primary tTG reactive sites. Mutating both residues to
      asparagine abolishes tTG-catalyzed cross-linking of alpha-syn and tTG-induced
      inhibition of alpha-syn fibrillization in vitro. To further elucidate the
      sequence and structural basis underlying these effects, we identified the lysine
      residues that form isopeptide bonds with Gln(79) and Gln(109). This study
      provides mechanistic insight into the sequence and structural basis of the
      inhibitory effects of tTG on alpha-syn fibrillogenesis in vivo, and it sheds
      light on the potential role of tTG cross-linking on modulating the physiological
      and pathogenic properties of alpha-syn.

PMID- 19164287
TI  - On the mechanism of a polyunsaturated fatty acid double bond isomerase from
      Propionibacterium acnes.
AB  - The catalytic mechanism of Propionibacterium acnes polyunsaturated fatty acid
      isomerase (PAI) is explored by kinetic, spectroscopic, and thermodynamic studies.
      The PAI-catalyzed double bond isomerization takes place by selective removal of
      the pro-R hydrogen from C-11 followed by suprafacial transfer of this hydrogen to
      C-9 as shown by conversion of C-9-deuterated substrate isotopologs. Data on the
      midpoint potential, photoreduction, and cofactor replacement suggest PAI to
      operate via an ionic mechanism with the formation of FADH(2) and linoleic acid
      carbocation as intermediates. In line with this proposal, no radical
      intermediates were detected neither by stopped flow absorption nor by EPR
      spectroscopy. The substrate preference toward free fatty acids is determined by
      the interaction between Arg-88 and Phe-193, and the reaction rate is strongly
      affected by replacement of these amino acids, indicating that the efficiency of
      the hydrogen transfer relies on a fixed distance between the free carboxyl group
      and the N-5 atom of FAD. Combining data obtained for PAI from the structural
      studies and experiments described here suggests that at least two different
      prototypical active site geometries exist among polyunsaturated fatty acid double
      bond isomerases.

PMID- 19164288
TI  - Neutralization of interleukin-18 ameliorates ischemia/reperfusion-induced
      myocardial injury.
AB  - Ischemia/reperfusion (I/R) injury is characterized by the induction of oxidative
      stress and proinflammatory cytokine expression. Recently demonstrating that
      oxidative stress and TNF-alpha each stimulate interleukin (IL)-18 expression in
      cardiomyocytes, we hypothesized that I/R also induces IL-18 expression and thus
      exacerbates inflammation and tissue damage. Neutralization of IL-18 signaling
      should therefore diminish tissue injury following I/R. I/R studies were performed
      using a chronically instrumented closed chest mouse model. Male C57BL/6 mice
      underwent 30 min of ischemia by LAD coronary artery ligation followed by various
      periods of reperfusion. Sham-operated or ischemia-only mice served as controls. A
      subset of animals was treated with IL-18-neutralizing antibodies 1 h prior to LAD
      ligation. Ischemic LV tissue was used for analysis. Our results demonstrate that,
      compared with sham operation and ischemia alone, I/R significantly increased (i)
      oxidative stress (increased MDA/4-HNE levels), (ii) neutrophil infiltration
      (increased MPO activity), (iii) NF-kappaB DNA binding activity (p50, p65), and
      (iv) increased expression of IL-18Rbeta, but not IL-18Ralpha or IL-18BP
      transcripts. Administration of IL-18-neutralizing antibodies significantly
      reduced I/R injury measured by reduced infarct size (versus control IgG). In
      isolated adult mouse cardiomyocytes, simulated ischemia/reperfusion enhanced
      oxidative stress and biologically active IL-18 expression via IKK-dependent NF
      kappaB activation. These results indicate that IL-18 plays a critical role in I/R
      injury and thus represents a promising therapeutic target.

PMID- 19164289
TI  - Peptides Targeting the Desmoglein 3 Adhesive Interface Prevent Autoantibody
      induced Acantholysis in Pemphigus.
AB  - Pemphigus vulgaris (PV) autoantibodies directly inhibit desmoglein (Dsg) 3
      mediated transinteraction. Because cellular signaling also seems to be required
      for PV pathogenesis, it is important to characterize the role of direct
      inhibition in pemphigus acantholysis to allow establishment of new therapeutic
      approaches. Therefore, we modeled the Dsg1 and Dsg3 sequences into resolved
      cadherin structures and predicted peptides targeting the adhesive interface of
      both Dsg3 and Dsg1. In atomic force microscopy single molecule experiments, the
      self-designed cyclic single peptide specifically blocked homophilic Dsg3 and Dsg1
      transinteraction, whereas a tandem peptide (TP) consisting of two combined single
      peptides did not. TP did not directly block binding of pemphigus IgG to their
      target Dsg antigens but prevented PV-IgG-induced inhibition of Dsg3
      transinteraction in cell-free (atomic force microscopy) and cell-based (laser
      tweezer) experiments, indicating stabilization of Dsg3 bonds. Similarly, PV-IgG
      mediated acantholysis and disruption of Dsg3 localization in HaCaT keratinocytes
      was partially blocked by TP. This is the first evidence that direct inhibition of
      Dsg3 binding is important for PV pathogenesis and that peptidomimetics
      stabilizing Dsg transinteraction may provide a novel approach for PV treatment.

PMID- 19164290
TI  - Rapid optimization of a peptide inhibitor of malaria parasite invasion by
      comprehensive N-methyl scanning.
AB  - Apical membrane antigen 1 (AMA1) of the malaria parasite Plasmodium falciparum
      has been implicated in the invasion of host erythrocytes and is an important
      vaccine candidate. We have previously described a 20-residue peptide, R1, that
      binds to AMA1 and subsequently blocks parasite invasion. Because this peptide
      appears to target a site critical for AMA1 function, it represents an important
      lead compound for anti-malarial drug development. However, the effectiveness of
      this peptide inhibitor was limited to a subset of parasite isolates, indicating a
      requirement for broader strain specificity. Furthermore, a barrier to the utility
      of any peptide as a potential therapeutic is its susceptibility to rapid
      proteolytic degradation. In this study, we sought to improve the proteolytic
      stability and AMA1 binding properties of the R1 peptide by systematic methylation
      of backbone amides (N-methylation). The inclusion of a single N-methyl group in
      the R1 peptide backbone dramatically increased AMA1 affinity, bioactivity, and
      proteolytic stability without introducing global structural alterations. In
      addition, N-methylation of multiple R1 residues further improved these
      properties. Therefore, we have shown that modifications to a biologically active
      peptide can dramatically enhance activity. This approach could be applied to many
      lead peptides or peptide therapeutics to simultaneously optimize a number of
      parameters.

PMID- 19164291
TI  - TORC2, a coactivator of cAMP-response element-binding protein, promotes Epstein
      Barr virus reactivation from latency through interaction with viral BZLF1
      protein.
AB  - Reactivation of the Epstein-Barr virus from latency is dependent on expression of
      the viral BZLF1 protein. The BZLF1 promoter (Zp) normally exhibits only low basal
      activity but is activated in response to chemical inducers such as 12-O
      tetradecanoylphorbol-13-acetate and calcium ionophore. We found here that
      Transducer of Regulated cAMP-response Element-binding Protein (CREB) (TORC) 2
      enhances Zp activity 10-fold and more than 100-fold with co-expression of the
      BZLF1 protein. Mutational analysis of Zp revealed that the activation by TORC is
      dependent on ZII and ZIII cis elements, binding sites for CREB family
      transcriptional factors and the BZLF1 protein, respectively. Immunoprecipitation,
      chromatin immunoprecipitation, and reporter assay using Gal4-luc and Gal4BD-BZLF1
      fusion protein indicate that TORC2 interacts with BZLF1, and that the complex is
      efficiently recruited onto Zp. These observations clearly indicate that TORC2
      activates the promoter through interaction with the BZLF1 protein as well as CREB
      family transcriptional factors. Induction of the lytic replication resulted in
      the translocation of TORC2 from cytoplasm to viral replication compartments in
      nuclei, and furthermore, activation of Zp by TORC2 was augmented by calcium
      regulated phosphatase, calcineurin. Silencing of endogenous TORC2 gene expression
      by RNA interference decreased the levels of the BZLF1 protein in response to 12-O
      tetradecanoylphorbol-13-acetate/ionophore. Based on these results, we conclude
      that Epstein-Barr virus exploits the calcineurin-TORC signaling pathway through
      interactions between TORC and the BZLF1 protein in reactivation from latency.

PMID- 19164292
TI  - Mapping of the C3d ligand binding site on complement receptor 2 (CR2/CD21) using
      nuclear magnetic resonance and chemical shift analysis.
AB  - Complement receptor 2 (CR2, CD21) is a cell membrane protein, with 15 or 16
      extracellular short consensus repeats (SCRs), that promotes B lymphocyte
      responses and bridges innate and acquired immunity. The most distally located
      SCRs (SCR1-2) mediate the interaction of CR2 with its four known ligands (C3d,
      Epstein-Barr virus gp350, interferon-alpha, and CD23). Inhibitory monoclonal
      antibodies against SCR1-2 block binding of all ligands. To develop ligand
      specific inhibitors that would also assist in identifying residues unique to each
      receptor-ligand interaction, phage were selected from randomly generated
      libraries by panning with recombinant SCR1-2, followed by specific ligand-driven
      elution. Derived peptides were tested by competition ELISA. One peptide, C3dp1
      (APQHLSSQYSRT) exhibited ligand-specific inhibition at midmicromolar IC(50). C3d
      was titrated into (15)N-labeled SCR1-2, which revealed chemical shift changes
      indicative of specific intermolecular interactions. With backbone assignments
      made, the chemical shift changes were mapped onto the crystal structure of SCR1
      2. With regard to C3d, the binding surface includes regions of SCR1, SCR2, and
      the inter-SCR linker, specifically residues Arg(13), Tyr(16), Arg(28), Tyr(29),
      Ser(32), Thr(34), Lys(48), Asp(56), Lys(57), Tyr(68), Arg(83), Gly(84), Asn(101),
      Asn(105), and Ser(109). SCR1 and SCR2 demonstrated distinct binding modes. The
      CR2 binding surface incorporating SCR1 is inconsistent with a previous x-ray CR2
      C3d co-crystal analysis but consistent with mutagenesis, x-ray neutron
      scattering, and inhibitory monoclonal antibody epitope mapping. Titration with
      C3dp1 yielded chemical shift changes (Arg(13), Tyr(16), Thr(34), Lys(48),
      Asp(56), Lys(57), Tyr(68), Arg(83), Gly(84), Asn(105), and Ser(109)) overlapping
      with C3d, indicating that C3dp1 interacts at the same CR2 site as C3d.

PMID- 19164293
TI  - Conversion of wild-type alpha-synuclein into mutant-type fibrils and its
      propagation in the presence of A30P mutant.
AB  - Fibrillization or conformational change of alpha-synuclein is central in the
      pathogenesis of alpha-synucleinopathies, such as Parkinson disease. We found that
      the A30P mutant accelerates nucleation-dependent fibrillization of wild type (WT)
      alpha-synuclein. Electron microscopy observation and ultracentrifugation
      experiments revealed that shedding of fragments occurs from A30P fibrils and that
      these fragments accelerate fibrillization by serving as seeds. Immunochemical
      analysis using epitope-specific antibodies and biochemical analyses of protease
      resistant cores demonstrated that A30P fibrils have a distinct conformation.
      Interestingly, WT fibrils formed with A30P seeds exhibited the same character as
      A30P fibrils, as did A30P fibrils formed with WT seeds, indicating that the A30P
      mutation affects the conformation and fibrillization of both WT and A30P. These
      effects of A30P mutation may explain the apparent conflict between the
      association of A30P with Parkinson disease and the slow fibrillization of A30P
      itself and therefore provide new insight into the molecular mechanisms of alpha
      synucleinopathies.

PMID- 19164294
TI  - Versican/PG-M Assembles Hyaluronan into Extracellular Matrix and Inhibits CD44
      mediated Signaling toward Premature Senescence in Embryonic Fibroblasts.
AB  - Versican/PG-M is a large chondroitin sulfate proteoglycan of the extracellular
      matrix which interacts with hyaluronan at the N-terminal G1 domain, composed of
      A, B, and B' subdomains. Recently, we generated knock-in mice
      Cspg2(Delta3/Delta3), whose versican, without the A subdomain, has decreased
      hyaluronan (HA) binding affinity, thereby exhibiting reduced deposition of
      versican in the extracellular matrix. Here, we show that the Cspg2(Delta3/Delta3)
      fibroblasts within 20 passages proliferate more slowly and acquire senescence.
      Whereas the extracellular matrix of the wild type fibroblasts exhibited a network
      structure of hyaluronan and versican, that of the Cspg2(Delta3/Delta3)
      fibroblasts exhibited approximately 35 and approximately 85% deposition of
      versican and HA, without such a structure. The Cspg2(Delta3/Delta3) fibroblasts
      showed a substantial increase of ERK1/2 phosphorylation and expression of
      senescence markers p53, p21, and p16. Treatment of wild type fibroblasts with
      hyaluronidase and exogenous hyaluronan enhanced ERK1/2 phosphorylation, and
      treatment with an anti-CD44 antibody that blocks HA-CD44 interaction inhibited
      the phosphorylation. These results demonstrate that versican is essential for
      matrix assembly involving hyaluronan and that diminished versican deposition
      increases free hyaluronan fragments that interact with CD44 and increase
      phosphorylation of ERK1/2, leading to cellular senescence.

PMID- 19164295
TI  - Ubiquitin Ligase RLIM Modulates Telomere Length Homeostasis through a Proteolysis
      of TRF1.
AB  - The telomeric protein TRF1 negatively regulates telomere length by inhibiting
      telomerase access at the telomere termini, suggesting that the protein level of
      TRF1 at telomeres is tightly regulated. Regulation of TRF1 protein abundance is
      essential for proper telomere function and occurs primarily through post
      translational modifications of TRF1. Here we describe RLIM, a RING H2 zinc finger
      protein with intrinsic ubiquitin ligase activity, as a TRF1-interacting protein.
      RLIM increases TRF1 turnover by targeting it for degradation by the proteasome in
      a ubiquitin-dependent manner, independently of Fbx4, which is known to interact
      with and negatively regulate TRF1. Whereas overexpression of RLIM decreases the
      level of TRF1 protein, depletion of endogenous RLIM expression by small hairpin
      RNA increases the level of TRF1 and leads to telomere shortening, thereby
      impairing cell growth. These results demonstrate that RLIM is involved in the
      negative regulation of TRF1 function through physical interaction and ubiquitin
      mediated proteolysis. Hence, RLIM represents a new pathway for telomere
      maintenance by modulating the level of TRF1 at telomeres.

PMID- 19164296
TI  - Binding and Cellular Activation Studies Reveal That Toll-like Receptor 2 Can
      Differentially Recognize Peptidoglycan from Gram-positive and Gram-negative
      Bacteria.
AB  - Although much progress has been made toward the identification of innate immune
      receptors, far less is known about how these receptors recognize specific
      microbial products. Such studies have been hampered by the need to purify
      compounds from microbial sources and a reliance on biological assays rather than
      direct binding to monitor recognition. We have employed surface plasmon resonance
      (SPR) binding studies using a wide range of well defined synthetic muropeptides
      derived from Gram-positive (lysine-containing) and Gram-negative (diaminopimelic
      acid (DAP)-containing) bacteria to demonstrate that Toll-like receptor 2 can
      recognize peptidoglycan (PGN). In the case of lysine-containing muropeptides, a
      limited number of compounds, which were derived from PGN remodeled by bacterial
      autolysins, was recognized. However, a wider range of DAP-containing muropeptides
      was bound with high affinity, and these compounds were derived from nascent and
      remodeled PGN. The difference in recognition of the two classes of muropeptides
      is proposed to be a strategy by the host to respond appropriately to Gram
      negative and -positive bacteria, which produce vastly different quantities of
      PGN. It was also found that certain modifications of the carboxylic acids of
      isoglutamine and DAP can dramatically reduce binding, and thus, bacterial strains
      may employ such modifications to evade innate immune detection. Cellular
      activation studies employing highly purified PGN from Bacillus licheniformis,
      Bacillus subtilis, Escherichia coli, Lactobacillus plantarum, Micrococcus luteus,
      and Staphylococcus aureus support the structure binding relationship. The data
      firmly establish Toll-like receptor 2 as an innate immune sensor for PGN and
      provides an understanding of host-pathogen interactions at the molecular level.

PMID- 19164297
TI  - Synthetic ciguatoxins selectively activate Nav1.8-derived chimeric sodium
      channels expressed in HEK293 cells.
AB  - The synthetic ciguatoxin CTX3C has been shown to activate tetrodotoxin (TTX)
      sensitive sodium channels (Na(v)1.2, Na(v)1.4, and Na(v)1.5) by accelerating
      activation kinetics and shifting the activation curve toward hyperpolarization
      (Yamaoka, K., Inoue, M., Miyahara, H., Miyazaki, K., and Hirama, M. (2004) Br. J.
      Pharmacol. 142, 879-889). In this study, we further explored the effects of CTX3C
      on the TTX-resistant sodium channel Na(v)1.8. TTX-resistant channels have been
      shown to be involved in transducing pain and related sensations (Akopian, A. N.,
      Sivilotti, L., and Wood, J. N. (1996) Nature 379, 257-262). Thus, we hypothesized
      that ciguatoxin-induced activation of the Na(v)1.8 current would account for the
      neurological symptoms of ciguatera poisoning. We found that 0.1 mum CTX3C
      preferentially affected the activation process of the Na(v)1.8 channel compared
      with those of the Na(v)1.2 and Na(v)1.4 channels. Importantly, without
      stimulation, 0.1 mum CTX3C induced a large leakage current (I (L)). The
      conductance of the I (L) calculated relative to the maximum conductance (G (max))
      was 10 times larger than that of Na(v)1.2 or Na(v)1.4. To determine the molecular
      domain of Na(v)1.8 responsible for conferring higher sensitivity to CTX3C, we
      made two chimeric constructs from Na(v)1.4 and Na(v)1.8. Chimeras containing the
      N-terminal half of Na(v)1.8 exhibited a large response similar to wild-type
      Na(v)1.8, indicating that the region conferring high sensitivity to ciguatoxin
      action is located in the D1 or D2 domains.

PMID- 19164298
TI  - N-Glycan Moieties in Neonatal Fc Receptor Determine Steady-state Membrane
      Distribution and Directional Transport of IgG.
AB  - The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I
      related molecule known to protect IgG and albumin from catabolism and transport
      IgG across polarized epithelial cells in a bidirectional manner. Previous studies
      have shown species-specific differences in ligand binding, IgG transport
      direction, and steady-state membrane distribution when expressed in polarized
      epithelial cells. We hypothesized that these differences may be due to the
      additional N-glycans expressed on the rat FcRn, because N-glycans have been
      proposed to function as apical targeting signals, and that two of the N-glycan
      moieties have been shown to contribute to the IgG binding of rat FcRn. A panel of
      mutant human FcRn variants was generated to resemble the N-glycan expression of
      rat FcRn in various combinations and subsequently transfected into Madin-Darby
      canine kidney II cells together with human beta2-microglobulin. Mutant human FcRn
      clones that contained additional N-glycan side-chain modifications, including
      that which was fully rodentized, still exhibited specificity for human IgG and
      failed to bind to mouse IgG. At steady state, the mutant human FcRn with
      additional N-glycans redistributed to the apical cell surface similar to that of
      rat FcRn. Furthermore, the rodentized human FcRn exhibited a reversal of IgG
      transport with predominant transcytosis from an apical-to-basolateral direction,
      which resembled that of the rat FcRn isoform. These studies show that the N
      glycans in FcRn contribute significantly to the steady-state membrane
      distribution and direction of IgG transport in polarized epithelia.

PMID- 19164299
TI  - Hyaluronan mediates ozone-induced airway hyperresponsiveness in mice.
AB  - Ozone is a common urban environmental air pollutant and significantly contributes
      to hospitalizations for respiratory illness. The mechanisms, which regulate ozone
      induced bronchoconstriction, remain poorly understood. Hyaluronan was recently
      shown to play a central role in the response to noninfectious lung injury.
      Therefore, we hypothesized that hyaluronan contributes to airway hyperreactivity
      (AHR) after exposure to ambient ozone. Using an established model of ozone
      induced airways disease, we characterized the role of hyaluronan in airway
      hyperresponsiveness. The role of hyaluronan in response to ozone was determined
      by using therapeutic blockade, genetically modified animals, and direct challenge
      to hyaluronan. Ozone-exposed mice demonstrate enhanced AHR associated with
      elevated hyaluronan levels in the lavage fluid. Mice deficient in either CD44
      (the major receptor for hyaluronan) or inter-alpha-trypsin inhibitor (molecule
      that facilitates hyaluronan binding) show similar elevations in hyaluronan but
      are protected from ozone-induced AHR. Mice pretreated with hyaluronan-binding
      peptide are protected from the development of ozone-induced AHR. Overexpression
      of hyaluronan enhances the airway response to ozone. Intratracheal instillation
      of endotoxin-free low molecular weight hyaluronan induces AHR dependent on CD44,
      whereas instillation of high molecular weight hyaluronan protects against ozone
      induced AHR. In conclusion, we demonstrate that hyaluronan mediates ozone-induced
      AHR, which is dependent on the fragment size and both CD44 and inter-alpha
      trypsin inhibitor. These data support the conclusion that pulmonary matrix can
      contribute to the development of airway hyperresponsiveness.

PMID- 19164300
TI  - Adherence to practice guidelines, clinical outcomes, and costs among Medicaid
      enrollees with severe mental illnesses.
AB  - The treatment of Medicaid enrollees diagnosed with depression or schizophrenia
      was examined to determine whether adherence to treatment guideline was associated
      with health care financing strategy, clinical outcomes, and cost-effectiveness.
      Individuals in a fee-for-service condition were significantly more likely to
      receive treatment consistent with guidelines than those in managed care. Mental
      health costs were higher for individuals diagnosed with schizophrenia,
      individuals in an acute phase of illness at intake into the study, and those
      receiving treatment consistent with practice guidelines. Being in an acute phase
      of illness and having treatment that comported with recommended practice
      guidelines were associated with higher total social costs. Policy implications of
      the findings and recommendations for future research are discussed.

PMID- 19164301
TI  - Endovascular port-a-cath insertion in a patient with cystic fibrosis and occluded
      superior vena cava.
AB  - INTRODUCTION: Port-a-cath insertion, for long-term intravenous antibiotic
      therapy, is an ideal solution for patient with cystic fibrosis. However,
      indwelling lines are liable to many complications including catheter thrombosis
      especially in patients having cystic fibrosis with hypercoagulable state.
      METHODS: An endovascular technique for insertion of a port-a-cath in a patient
      having cystic fibrosis with occluded superior vena cava is reported. The
      technique is described in detail. In addition, a review of literature for the
      various methods of saving a failed central venous access in these patients was
      performed. RESULTS: The line was successfully inserted and remained patent
      without need of any further intervention for 20 months. CONCLUSION: In this
      report, several endovascular skills were used for central venous access salvage
      that can be used in similar situations with chronic superior vena cava occlusion,
      which may not be suitable for thrombolysis or stenting.

PMID- 19164302
TI  - New evaluation measures for multifactor dimensionality reduction classifiers in
      gene-gene interaction analysis.
AB  - MOTIVATION: Gene-gene interactions are important contributors to complex
      biological traits. Multifactor dimensionality reduction (MDR) is a method to
      analyze gene-gene interactions and has been applied to many genetics studies of
      complex diseases. In order to identify the best interaction model associated with
      disease susceptibility, MDR classifiers corresponding to interaction models has
      been constructed and evaluated as a predictor of disease status via a certain
      measure such as balanced accuracy (BA). It has been shown that the performance of
      MDR tends to depend on the choice of the evaluation measures. RESULTS: In this
      article, we introduce two types of new evaluation measures. First, we develop
      weighted BA (wBA) that utilizes the quantitative information on the effect size
      of each multi-locus genotype on a trait. Second, we employ ordinal association
      measures to assess the performance of MDR classifiers. Simulation studies were
      conducted to compare the proposed measures with BA, a current measure. Our
      results showed that the wBA and tau(b) improved the power of MDR in detecting
      gene-gene interactions. Noticeably, the power increment was higher when data
      contains the greater number of genetic markers. Finally, we applied the proposed
      evaluation measures to real data.

PMID- 19164303
TI  - SIMPRO: simple protein homology detection method by using indirect signals.
AB  - MOTIVATION: Detecting homologous proteins is one of the fundamental problems in
      computational biology. Many tools to solve this problem have been developed, but
      development of a simple, effective and generally applicable method is still
      desirable. RESULTS: We propose a simple but effective information retrieval
      approach, named SIMPRO, to identify homology relationship between proteins. The
      key idea of our approach is that by accumulating and comparing indirect signals
      from conventional homology search methods, the search sensitivity can be
      increased. We tested the idea on the problem of detecting homology relationship
      between Pfam families, as well as detecting structural homologs based on SCOP,
      and found that our method achieved significant improvement. Our results indicate
      that simple manipulation of conventional homology search outputs by SIMPRO
      algorithm can remarkably improve homology search accuracy.

PMID- 19164304
TI  - Properties and identification of human protein drug targets.
AB  - MOTIVATION: We analysed 148 human drug target proteins and 3573 non-drug targets
      to identify differences in their properties and to predict new potential drug
      targets. RESULTS: Drug targets are rare in organelles; they are more likely to be
      enzymes, particularly oxidoreductases, transferases or lyases and not ligases;
      they are involved in binding, signalling and communication; they are secreted;
      and have long lifetimes, shown by lack of PEST signals and the presence of N
      glycosylation. This can be summarized into eight key properties that are
      desirable in a human drug target, namely: high hydrophobicity, high length,
      SignalP motif present, no PEST motif, more than two N-glycosylated amino acids,
      not more than one O-glycosylated Ser, low pI and membrane location. The sequence
      features were used as inputs to a support vector machine (SVM), allowing the
      assignment of any sequence to the drug target or non-target classes with an
      accuracy in the training set of 96%. We identified 668 proteins (23%) in the non
      target set that have target-like properties. We suggest that drug discovery
      programmes would be more likely to succeed if new targets are chosen from this
      set or their homologues.

PMID- 19164305
TI  - Influence of HyCoSy on spontaneous pregnancy: a randomized controlled trial.
AB  - BACKGROUND: The aim of the study was to test whether the use of sonography
      contrast could enhance the chance of spontaneous clinical pregnancy in women
      undergoing subfertility investigation. METHODS: Couples with at least 1 year of
      infertility who were scheduled for a consultation including a hysterosalpingo
      contrast sonography (HyCoSy) were invited to participate in the study. We
      compared flushing with water-soluble contrast medium (WSCM) versus no flushing.
      Randomization sequence was computer generated, stratified for age and group
      allocation was concealed. Primary outcome was clinical pregnancy defined as a
      sonographically visible fetal sac, detected within 6 months from randomization.
      Secondary outcomes were spontaneous miscarriage and birth. Exclusion criteria
      were female age >or=40 years, severe male infertility, previously known severe
      tubal infertility and suspected anovulation. RESULTS: The mean age of the study
      population (n = 334) was 31.9 years. Duration of infertility was 2.1 years. The
      clinical pregnancy rate was 29.2% in the HyCoSy group and 26.5% in the non
      flushing group, the difference being 2.7% (95% confidence interval -6.9 to 12.3%,
      P = 0.63). CONCLUSION: The clinical impression of an enhanced pregnancy rate
      after performing HyCoSy could not be confirmed. Tubal investigation with
      sonography using water-soluble contrast has a function as a diagnostic procedure
      but not in terms of increasing pregnancy rates in subfertile patients. TRIAL
      REGISTRATION NUMBER: ISRCTN20715945.

PMID- 19164306
TI  - Parental information sharing with donor insemination conceived offspring: a
      follow-up study.
AB  - BACKGROUND: Studies of parental decision making regarding information sharing
      with offspring conceived as a result of donor insemination are almost all based
      on a 'one point in time' design. This study reports on parental decision making
      at two points in time, Time 1 and Time 2, 14 years apart. METHODS: Forty-four of
      57 families (77%) who had agreed to take part in a follow-up study were
      interviewed. An in-depth semi-structured interview format was used. In addition,
      two questionnaires seeking mainly quantitative data were administered. RESULTS:
      Fifteen families (35%) had told their offspring of the donor insemination
      conception at Time 2 (2004). An additional seven families said they had always
      wanted or intended to tell the children and asked for assistance on how to do
      this. Where partners were in agreement on information sharing at Time 1 (1990)
      either to tell or not to tell-this position was maintained. Where there was
      disagreement, or uncertainty, two-thirds had not told and one-third had.
      CONCLUSIONS: Despite the professional and socio-political culture at the time of
      treatment, almost half of the families in this study ended up sharing the donor
      insemination conception with their offspring. The results support the need for
      appropriate preparation for donor insemination family building.

PMID- 19164307
TI  - ICRU: a historical perspective of 90 years of radiation science.

PMID- 19164308
TI  - Evaluation of the therapeutic results of epiduroscopic adhesiolysis for failed
      back surgery syndrome.
AB  - BACKGROUND: No data for patients with failed back surgery syndrome (FBSS) based
      on the location of adhesions separated by epiduroscopic adhesiolysis have been
      reported. METHODS: We performed epiduroscopic adhesiolysis on 28 FBSS patients to
      examine the impact of differences in the locations of the separated regions on
      the treatment results. We performed fluoroscopic imaging through the sacral
      hiatus to assess the condition of adhesions in the epidural space during the post
      adhesiolysis observation period. RESULTS: In patients in whom only the epidural
      space was separated by adhesiolysis, there was a significant improvement in the
      Roland-Morris disability questionnaire (RDQ) score until 12 weeks after
      adhesiolysis, but the score gradually returned to the preoperative value
      thereafter. Among patients in whom the nerve root responsible for radicular pain
      was separated, there was a long-term improvement in the RDQ, Oswestry disability
      index 2.0 (ODI), and Japanese Orthopedic Association Assessment of Treatment
      (JOA) scores. Among patients in whom both the epidural space and the nerve root
      responsible for pain were separated, there was a 12 week improvement in the RDQ
      score and 24 week improvements in the ODI and JOA scores. CONCLUSIONS:
      Progressive epidural imaging after adhesiolysis suggested that pain was caused by
      re-adhesion around the nerve root. Since re-adhesion of the nerve root required
      some time, the effect of adhesiolysis was maintained for extended periods in
      these cases. We suggest that epiduroscopic adhesiolysis is an effective therapy
      for FBSS patients, and that adhesiolysis of the nerve root may exhibit the long
      term (24 weeks) efficacy in patients with pain.

PMID- 19164309
TI  - Swyer-James-MacLeod syndrome; repeated chest drainages in a patient misdiagnosed
      with pneumothorax.
AB  - Swyer-James-MacLeod Syndrome (SJMS) occurs as a result of childhood bronchiolitis
      obliterans. Typically, this disorder is diagnosed in childhood after evaluations
      for recurrent respiratory infections. One of the reasons to explain the
      difficulty in diagnosis is that when patients develop little bronchiectasis, and
      therefore, few symptoms, then this syndrome may not be recognized until
      adulthood. Here, we are presenting a 22-year-old female patient who was diagnosed
      with SJMS who was initially misdiagnosed with a pneumothorax and treated by
      multiple chest tube drainages. This case highlights the significance of taking a
      careful history, the application of computed tomography and scintigraphy in
      confirming the diagnosis of SJMS and in eliminating other diseases.

PMID- 19164310
TI  - Spontaneous bronchopleural fistula following lung volume reduction surgery for
      emphysema.
AB  - Five days following bilateral thoracoscopic lung volume reduction surgery for
      emphysema, a 63-year-old man underwent reoperation for closure of a massive
      bronchopleural fistula. It was discovered intraoperatively that the fistula was
      located distant from prior staple lines or resection sites from his surgery. This
      case is an example of what may be a unique pathophysiologic mechanism of
      bronchopleural fistula formation--a 'stress rupture' of the lung parenchyma
      following lung volume reduction surgery.

PMID- 19164311
TI  - eComment: Re: Acute onset of paraplegia after repair of abdominal aortic aneurysm
      in a patient with acute type B aortic dissection 30 December 2008.

PMID- 19164312
TI  - eComment: Anticoagulation for mechanical heart valves: a current assessment.

PMID- 19164313
TI  - eComment: Aortic dissection and confusing nomenclature.

PMID- 19164314
TI  - eComment: Congenital absence of the left pulmonary artery: the feasibility of an
      'ideal' correction.

PMID- 19164315
TI  - eComment: Retrograde aortic stent graft compression in the mid- and long-term run
      after endovascular repair of type 3B aortic dissecting aneurysms.

PMID- 19164317
TI  - Trends in colorectal cancer incidence by subsite in Osaka, Japan.
AB  - To date, the time trends of left-to-right shift of colorectal cancer incidence
      have been reported in Western countries. In the present study, we calculated the
      average annual number of colorectal cancer incidence and the age-adjusted
      colorectal rates, and examined the change of subsite distribution using the data
      from the Osaka Cancer Registry between 1974 and 2003. Mucosal carcinoma cases
      were excluded from the analyses. The proportions of right colon cancer among all
      colorectal cancer cases were consistently increased; from 21.5% in 1974-78 to
      25.6% in 1999-2003 among men, and from 28.2% in 1974-78 to 36.8% in 1999-2003
      among women. The age-adjusted incidence rates of right colon cancer among men and
      women recently levelled off, while the rates of left colon and rectal cancers
      showed a declining trend. Among women, right colon cancer was more common in the
      elderly than in the young. The change of subsite distribution seemed to be
      associated with population aging, changes of life style and the development of
      total colonoscopy. Careful monitoring is necessary to confirm these findings.

PMID- 19164318
TI  - Weekly administration of epoetin beta for chemotherapy-induced anemia in cancer
      patients: results of a multicenter, Phase III, randomized, double-blind, placebo
      controlled study.
AB  - OBJECTIVE: The efficacy and safety of weekly administration of epoetin beta (EPO)
      for chemotherapy-induced anemia (CIA) patients was evaluated. METHODS: One
      hundred and twenty-two patients with lung cancer or malignant lymphoma undergoing
      chemotherapy were randomized to the EPO 36 000 IU group or the placebo group.
      Hematological response and red blood cell (RBC) transfusion requirement were
      assessed. Quality of life (QOL) was assessed using the Functional Assessment of
      Cancer Therapy-Anemia (FACT-An) questionnaire. RESULTS: Mean change in hemoglobin
      level with EPO increased significantly over placebo (1.4 +/- 1.9 g/dl versus -0.8
      +/- 1.5 g/dl; P < 0.001). The proportion of patients with change in hemoglobin
      level > or =2.0 g/dl was higher for EPO than those for placebo (P < 0.001). After
      4 weeks of administration, the proportion of RBC transfusion or hemoglobin level
      <8.0 g/dl was significantly lower for EPO than those for placebo (P = 0.046). The
      changes in the FACT-An total Fatigue Subscale Score (FSS) were less deteriorated
      with EPO than those with placebo. Progressive disease (PD) did not influence the
      change in hemoglobin level but there was less decrease in FSS in non-PD patients.
      No significant differences in adverse events were observed. Thrombovascular
      events and pure red cell aplasia related to EPO were not observed. Retrospective
      analysis of survival showing the hazard ratio of EPO to placebo was 0.94.
      CONCLUSION: Weekly administration of EPO 36 000 IU significantly increased
      hemoglobin level and ameliorated the decline of QOL in CIA patients over the 8
      week administration period.

PMID- 19164319
TI  - Outcomes of critically ill patients with acute kidney injury and end-stage renal
      disease requiring renal replacement therapy: a case-control study.
AB  - BACKGROUND: This study aimed to evaluate and compare the characteristics and
      outcomes of patients with end-stage renal disease (ESRD) with those of matched
      controls of patients with acute kidney injury (AKI) requiring renal replacement
      therapy. METHODS: A case-control study was performed at the intensive care units
      (ICU) of three tertiary-care hospitals between December 2004 and September 2007.
      Patients were admitted with life-threatening complications and were matched for
      age and for severity of illness and organ dysfunctions. Conditional logistic
      regression was used to identify factors associated with hospital mortality.
      RESULTS: A total of 54 patients with ESRD and 54 patients with AKI were eligible
      for the study and were well matched. In general, clinical characteristics were
      similar. Nonetheless, comorbidities were more frequent in patients with ESRD, and
      patients with AKI more frequently required mechanical ventilation. ICU (43%
      versus 20%, P = 0.023) and hospital (50% versus 24%, P = 0.010) mortality rates
      were higher in patients with AKI. In addition, patients with AKI experienced
      longer ICU and hospitals stays. The SAPS II score had a regular ability in
      discriminating survivors and non-survivors, and tended to underestimate mortality
      in patients with AKI and overestimate in patients with ESRD. When all patients
      were evaluated, older age [OR = 1.05 (95% CI, 1.01-1.09)], poor chronic health
      status [OR = 3.90(1.19-12.82)] and number of associated organ failures [OR =
      4.44(1.97-10.00)] were the main independent predictors of mortality. After
      adjusting for those covariates, ESRD was still associated with a lower
      probability of death [OR = 0.17 (0.06-0.050)]. CONCLUSIONS: ESRD patients with
      life-threatening complications had significantly better outcome than AKI
      patients.

PMID- 19164320
TI  - Aortic calcification predicts cardiovascular events and all-cause mortality in
      renal transplantation.
AB  - BACKGROUND: Cardiovascular disease is a leading cause of death among renal
      transplant recipients. Aortic calcification is associated with increased
      mortality in dialysis subjects. The significance of aortic calcification among
      renal transplant recipients is unknown. Our objective was to prospectively
      examine the association of aortic calcification with cardiovascular events and
      all-cause mortality among asymptomatic incident renal transplant recipients.
      METHODS: One hundred and twelve renal transplant recipients underwent electron
      beam computed tomography. Aortic calcification was scored by the Agatston method.
      The mean follow-up time was 5.1 years. Cardiovascular events (heart failure,
      coronary artery disease, peripheral arterial disease and stroke) and all-cause
      mortality were recorded. RESULTS: The cohort consisted of 62% Caucasians, 38%
      African Americans and 62% male gender. The mean age was 49.0 +/- 12.5 years.
      Thirty-four percent had aortic calcification. During follow-up, 12 cardiovascular
      events and 10 deaths were recorded. Subjects with aortic calcification had more
      cardiovascular events compared to those without aortic calcification (23.7 versus
      4.1%, P = 0.001). Recipients with aortic calcification had higher mortality
      compared to those without aortic calcification but it did not reach statistical
      significance (15.8 versus 5.4%, P = 0.07). The univariate hazard ratio of aortic
      calcification score in a proportional hazard Cox model to assess event-free
      survival was 1.15 (1.04-1.27, P = 0.01). Diabetes and aortic calcification score
      were independently associated with survival. In addition to the predictors above,
      dialysis vintage was an independent predictor for combined future cardiovascular
      event and mortality. CONCLUSIONS: In conclusion, aortic calcification is
      prevalent among renal transplant recipients and is predictive of future
      cardiovascular events. Aortic calcification is easily identified by non-invasive
      testing, and should be considered when assessing cardiovascular risk in
      asymptomatic renal transplant recipients.

PMID- 19164321
TI  - Silent recovery of native kidney function after transplantation in a patient with
      membranous nephropathy.
AB  - Recurrence of membranous nephropathy (MN) is frequently seen after
      transplantation. However, there are no published data about the course of MN in
      the native kidneys after transplantation. Disease progression in almost all cases
      is assumed to be the 'natural' course after transplantation. We report on a
      patient suffering from end-stage renal disease due to MN. Eight years after
      transplantation, nephrectomy was performed due to chronic rejection and
      unexpectedly, partial recovery of native kidney function was noted. As far as we
      know, there is no other similar case reported in the literature. The potential
      impact of the immunosuppression, especially of calcineurin inhibitors, is
      discussed.

PMID- 19164322
TI  - Adiponectin is positively associated with insulin resistance in subjects with
      type 2 diabetic nephropathy and effects of angiotensin II type 1 receptor blocker
      losartan.
AB  - BACKGROUND: Plasma adiponectin concentration is inversely associated with renal
      function. There is little literature on adiponectin levels and regulation by anti
      hypertensive medication with an angiotensin II type 1 receptor blocker (ARB),
      especially in subjects with type 2 diabetes in different stages of chronic kidney
      disease (CKD). METHODS: Eighty subjects with type 2 diabetic nephropathy were
      randomly divided into two groups: losarten group (n = 41) and amlodipine group (n
      = 39). Fasting blood was drawn to determine HbA1c, insulin and adiponectin
      levels. Insulin resistance was calculated using fasting glucose and insulin,
      expressed as HOMA-IR. For assessment of the relationship between adiponectin and
      other parameters, Pearson sample correlation coefficients were used. After
      stratification, ARB losartan (100 mg daily) was administered for a period of 6
      months. RESULTS: There is a positive association between adiponectin and
      proteinuria, fasting insulin levels and HOMA-IR in both CKD stage 1-2 and stage 3
      4. Baseline adiponectin levels were not related to baseline estimated glomerular
      filtration rate (eGFR). At baseline, the adiponectin concentration was high in
      all observed subjects, and after 3 and 6 months of treatment with losartan,
      adiponectin levels decreased in the losartan group as compared with the
      amlodipine group (P < 0.01). Also fasting insulin and HOMA-IR decreased during
      the 6-month follow-up compared with the control group (P < 0.01). CONCLUSION: Our
      results demonstrate that serum adiponectin levels in type 2 diabetic nephropathy
      are strongly positively associated with fasting insulin levels and insulin
      resistance. Declines in fasting insulin and HOMA-IR by losartan are accompanied
      by decreased adiponectin levels, might offer potential protection in humans. The
      paradoxical phenomenon merits further ascertainment in future studies.

PMID- 19164323
TI  - Circulating angiopoietin-2 is a marker and potential mediator of endothelial cell
      detachment in ANCA-associated vasculitis with renal involvement.
AB  - BACKGROUND: The endothelial-specific angiopoietin (Ang)-Tie ligand-receptor
      system has been identified as a non-redundant regulator of endothelial cell
      detachment in vitro. Binding of circulating angiopoietin-2 (Ang-2) to the Tie2
      receptor antagonizes Tie2 signalling and leads to disassembly of cell-cell
      junctions. Here, we ask whether circulating Ang-2 correlates with the severity of
      endothelial damage in ANCA-associated vasculitis (AAV) with renal involvement.
      METHODS: Ang-2 was measured in sera obtained from 45 patients with AAV and 20
      healthy controls by in-house ELISA. The disease activity was monitored by BVAS
      and the enumeration of circulating endothelial cells (CECs). RESULTS: Ang-2 was
      significantly elevated in active AAV with renal involvement compared to controls
      and patients in remission. In contrast, Ang-2 was normal in patients with active
      granulomatous disease limited to the respiratory tract. Linear regression
      analysis demonstrated a strong association of Ang-2 with BVAS (r(s)(2) = 0.49 P <
      0.0001) and the number of CECs (r(s)(2) = 0.48 P < 0.001). An Ang-2 cut-off value
      >4.15 ng/ml for a positive result yielded 100% specificity and 65% sensitivity
      for active systemic vasculitis. The positive predictive value was 99% and the
      negative predictive value 84%. CONCLUSIONS: Circulating Ang-2 is elevated and
      closely correlates with BVAS and CEC numbers in AAV with renal involvement. These
      data indicate that Ang-2 might be a potential mediator of endothelial cell
      detachment in AAV.

PMID- 19164324
TI  - Systemic inflammation is associated with pulmonary hypertension in patients
      undergoing haemodialysis.
AB  - BACKGROUND: Pulmonary hypertension (PH) is an overlooked cardiovascular morbidity
      in patients undergoing haemodialysis. Inflammation has been demonstrated to play
      a significant role with certain types of PH in non-uraemic patients, but studies
      analysing the mechanisms in dialyzed patients with PH are rare. Hence, we
      investigated systemic and local inflammation biomarkers associated with PH in
      uraemia patients to elucidate the potential mechanism. METHODS: A cross-sectional
      study was conducted in which 97 haemodialysis patients were initially evaluated
      in our hospital. Twelve inflammatory cytokines were measured using a cytometric
      beads assay in patients with and without PH. FE(NO) (fractional exhaled nitric
      oxide) was checked by a chemiluminescence analyser in patients with and without
      PH as well as by normal controls. RESULTS: Thirty-nine eligible patients were
      enrolled. Compared to patients without PH (group A), patients with PH (group B)
      had significantly higher serum levels of hs-CRP, IL-1beta, TNF-alpha and IL-6.
      FE(NO) was also measured. Though the pre-dialysis FE(NO) levels were elevated in
      both groups; group B patients had significantly higher pre-dialysis FE(NO) levels
      than group A patients (39.9 +/- 16.7 versus 31.8 +/- 10.3, P = 0.045). The post
      dialysis FE(NO) levels returned to normal in group A while the remaining were
      significantly higher in group B (30.3 +/- 10.3 versus 20.1 +/- 10.9, P = 0.003).
      CONCLUSIONS: Our study revealed that dialyzed patients with PH had a
      significantly higher level of airway FE(NO) as well as serum levels of acute
      phase reactive protein and cytokines, including IL-1beta, TNF-alpha and IL-6. A
      chronic inflammation might play an important role in the pathogenesis of PH in
      patients undergoing haemodialysis.

PMID- 19164325
TI  - Prediction of the severity and outcome of acute tubular necrosis based on
      continuity of Doppler spectrum in the early period after kidney transplantation.
AB  - BACKGROUND: Doppler flow spectrum, quantified in the segmental arteries of the
      graft early after kidney transplantation (KTx), reflects the exacerbation of
      interstitial oedema. In some patients, the spectrum is characterized by the
      absence of blood flow during part or during the whole diastole of the cardiac
      cycle. We have previously observed that such discontinuous flow is associated
      with a more severe clinical course of acute tubular necrosis (ATN). In order to
      further verify this hypothesis, we have quantified prospectively the timing of
      blood flow in Doppler spectrum within the cardiac cycle. METHODS: Doppler
      sonography was performed in 173 recipients between 2 and 4 days after KTx. A
      total of 18 patients with a diagnosed episode of acute rejection or primary graft
      non-function were excluded from the analysis. Fifty-three out of 155 patients
      (34%) developed ATN, defined as a requirement for more than one haemodialysis
      session after KTx. In patients with a discontinuous spectrum of flow, we have
      quantified the ratio of time during the whole cardiac cycle in which the flow is
      present [flow time index (FTI) expressed as %]. RESULTS: The discontinuous
      spectrum of flow was present in 35 out of 53 (66.0%) patients with ATN but only
      in 6 out of 102 (5.9%) patients with immediate or slow graft function. The
      relative risk of ATN occurrence for patients with discontinuous spectrum of flow
      was 5.98 (3.83-9.34) and the duration of ATN in these patients was twice as long
      12 (10-14) versus 6 (5-8) days. In patients with ATN a significant correlation
      was found between FTI and duration of ATN (r = -0.357, P = 0.035). CONCLUSION:
      The discontinuous spectrum of flow in the segmental arteries of the kidney graft
      in the early period after KTx is typical for ATN and predicts its duration.

PMID- 19164326
TI  - Indoxyl sulphate induces oxidative stress and the expression of osteoblast
      specific proteins in vascular smooth muscle cells.
AB  - BACKGROUND: Previously, we demonstrated that indoxyl sulphate (IS), a uraemic
      toxin, induced aortic calcification in hypertensive rats. This study aimed to
      determine if IS induces the production of reactive oxygen species (ROS) and the
      expression of osteoblast-specific proteins in human aortic smooth muscle cells
      (HASMCs). METHODS: In order to achieve these goals, HASMCs were incubated with
      IS. ROS were detected using probes with a fluorescence detector. The expression
      of alkaline phosphatase (ALP), osteopontin and organic anion transporters (OAT1,
      OAT3) was studied by western blotting. The expression of core binding factor 1
      (Cbfa1), ALP, osteopontin and NADPH oxidases (Nox1, Nox2 and Nox4) was analysed
      by reverse transcription-polymerase chain reaction (RT-PCR). Knockdown of Nox4
      was performed by RNA interference (RNAi). RESULTS: IS induced ROS generation and
      the expression of Nox4, Cbfa1, ALP and osteopontin in HASMCs. A NADPH oxidase
      inhibitor and antioxidants inhibited IS-induced ROS production and mRNA
      expression of Cbfa1 and ALP. Knockdown of Nox4 using small interfering RNA
      (siRNA) inhibited IS-induced ROS production and mRNA expression of Cbfa1, ALP and
      osteopontin. OAT3 was expressed in HASMCs. CONCLUSIONS: IS induces ROS generation
      by upregulating Nox4, and the expression of osteoblast-specific proteins such as
      Cbfa1, ALP and osteopontin in HASMCs.

PMID- 19164327
TI  - Interferon-gamma release assays versus tuberculin skin testing for detection of
      latent tuberculosis in chronic haemodialysis patients.
AB  - BACKGROUND: End stage renal disease increases the risk of reactivating latent
      tuberculosis (LTBI). Interferon-gamma release assays (IGRA) are an alternative to
      the tuberculin skin test (TST) for detecting LTBI. METHODS: Sixty-two
      hemodialysis patients (46 male, 16 female, aged 65 +/- 15 years) from 3
      hemodialysis facilities in the Geneva area were submitted to a TST, 2 IGRA (T
      SPOT.TB and QuantiFERON Gold in tube: QFT), a chest radiography, and a
      questionnaire to record social status, country of birth, history of prior TST,
      tuberculosis (TB), BCG (Bacillus of Calmette-Guerin vaccine), and any cause of
      immuno-suppression. LTBI was defined as prior "at risk" contact with a case of
      contagious TB and/or a chest X-ray suggestive of prior TB infection. RESULTS:
      Positivity rate was 19% for TST, 21% for QFT and 29% for T-SPOT-TB; 8% of QFT and
      11% of T-SPOT-TB were indeterminate. Agreement between IGRA was fair (kappa =
      0.60). After adjusting for age and BCG, OR (Odds Ratio) of having a positive QFT
      was 4.6-fold (p = 0.029) higher in patients with LTBI vs. those without LTBI. In
      contrast, no association was found between LTBI and having a positive T-SPOT.TB
      or a positive TST. As expected, there was a strong association between prior BCG
      vaccination and having a positive TST (OR 5.3, p = 0.017). QFT was the only test
      with a significant OR of having LTBI (adjusted OR: 4.4; 95%CI: 1.1 - 17.6; p =
      0.034). Among 5 patients with definite prior TB, TST and T-SPOT.TB were positive
      in 1 and QFT, in 2. CONCLUSIONS: In this population, QFT was superior to TST for
      detecting LTBI, but both IGRAs and TST have important limitations, and are
      unreliable for screening for LTBI.

PMID- 19164328
TI  - Occupational exposures and asthma among nursing professionals.
AB  - OBJECTIVES: To identify occupational exposure risk factors associated with the
      development of new-onset asthma in nurses. METHODS: A cross-sectional survey was
      administered to a sample of licensed Texas nurses (response rate 70%) and
      compared to three other healthcare professional groups. Nursing professionals
      were defined based on self-reported longest held job. Outcome variables were
      physician-diagnosed new-onset asthma after entry into the healthcare profession
      and symptoms associated with bronchial hyper-responsiveness (BHR). Occupational
      exposures were ascertained through a job-exposure matrix, grouped into four
      categories: cleaning-related tasks, use of powdered latex gloves, administration
      of aerosolised medications, and tasks involving adhesive compounds, glues and/or
      solvents. RESULTS: After adjustment for age, sex, ethnicity, atopy, smoking, body
      mass index and seniority, reported asthma was significantly greater among nursing
      professionals involved in medical instrument cleaning (OR = 1.67, 95% CI 1.06 to
      2.62) and exposure to general cleaning products and disinfectants (OR = 1.72, 95%
      CI 1.00 to 2.94). Use of powdered latex gloves during 1992-2000 was associated
      with 1.6 times (95% CI 1.01 to 2.50) the odds of reported asthma. In univariate
      analysis, exposure to adhesives, glues and/or solvents was associated with a
      twofold increase in the odds of reported asthma, but not after adjustment for
      covariates. Similarly, the odds of BHR-related symptoms were significantly
      greater among nursing professionals exposed to general cleaning products and
      disinfectants (OR = 1.57, 95% CI 1.11 to 2.21) and adhesives, glues and/or
      solvents used in patient care (OR = 1.51, 95% CI 1.08 to 2.12). CONCLUSION: Among
      nursing professionals, workplace exposures to cleaning products and disinfectants
      increase the risk of new-onset asthma.

PMID- 19164329
TI  - Risk of death after first admission for cardiovascular diseases by country of
      birth in The Netherlands: a nationwide record-linked retrospective cohort study.
AB  - OBJECTIVE: To examine differences in short- (28 days) and long-term (5 years)
      risk of death in patients hospitalised for the first time for various
      cardiovascular diseases (CVD) by country of birth and/or parental country of
      birth. DESIGN: A nationwide prospective cohort of CVD patients. SETTINGS: Entire
      Netherlands. PATIENTS: 118 691 patients hospitalised for the first time for
      various CVDs were identified through the national hospital discharge, the Dutch
      population and the cause-of-death registers. MAIN OUTCOME MEASURES: Differences
      in short-term and long-term risk of death. Cox proportional hazard models were
      used to estimate the mortality hazard ratios. RESULTS: After adjusting for age,
      compared with Dutch patients, Turkish, other non-Western and Western migrants had
      both a short- and long-term higher risk, while Suriname patients had only a long
      term higher risk of total-mortality and combined-CVD mortality. These higher
      rates were driven mainly by an increased risk of short-term (hazard ratio 3.21;
      95% CI 1.03 to 10.03) and long-term (2.29; 1.14 to 4.60) mortality following
      congestive heart failure (CHF) among Turkish; short-term (1.56; 1.10 to 2.20) and
      long-term (1.50; 1.11 to 2.01) mortality following cerebrovascular accident (CVA)
      among the other non-Western migrants; short-term mortality following CVA (1.10;
      1.01 to 1.19) and long-tem mortality following CVA (1.10; 1.03 to 1.17), and, to
      a lesser extent, CHF and myocardial infarction among Western migrants; and a long
      term mortality following CVA (1.29; 1.05 to 1.57) among Surinamese patients.
      CONCLUSION: Higher mortality after a first episode of CVD was found in ethnic
      minority patients than in Dutch patients. These differences hardly changed after
      adjusting for possible confounders, suggesting that treatment and secondary
      prevention strategies may be less effective in these groups. More research is
      needed to explain the possible causes of these inequalities.

PMID- 19164330
TI  - Cardiac adrenergic nerve function and microvascular dysfunction in patients with
      cardiac syndrome X.
AB  - OBJECTIVE: To assess whether abnormalities in cardiac uptake of (123)I
      metaiodobenzylguanidine (MIBG) correlate with coronary microvascular dysfunction
      in patients with cardiac syndrome X (CSX). SETTING: University hospital.
      PATIENTS: 29 patients (aged 59 (SD 7) years, 11 men) with typical CSX and a
      matched group of 20 healthy subjects (aged 56 (7) years, 8 men) were studied.
      INTERVENTIONS: Planar and single photon emission computed tomography (SPECT) MIBG
      myocardial scintigraphy was performed in all subjects. Coronary flow response
      (CFR) to adenosine and to cold pressor test (CPT) in the left anterior descending
      (LAD) coronary artery was assessed in all CSX patients and in 12 controls by
      transthoracic Doppler echocardiography. MAIN OUTCOME MEASURES: Abnormalities in
      cardiac MIBG scintigraphy were observed in 25 CSX patients (86.2%), but in no
      healthy control (p<0.001). Compared to controls, CSX patients showed a lower
      heart/mediastinum (H/M) ratio of MIBG uptake (1.69 (0.24) vs 2.2 (0.3), p<0.001)
      and a higher cardiac MIBG defect score (25 (22) vs 4 (2), p = 0.002). Both CFR to
      adenosine (3.31 (1.1) vs 1.94 (0.6), p<0.001) and CFR to CPT (2.35 (0.5) vs 1.63
      (0.4), p<0.001) were lower in CSX patients than in controls. In CSX patients,
      however, no correlation was found between MIBG H/M ratio and CFR to adenosine (r
      = 0.17; p = 0.38) and to CPT (r = -0.28; p = 0.13), as well as between MIBG
      uptake score in the LAD territory and CFR to adenosine (r = 0.14; p = 0.47) and
      to CPT (r = 0.06; p = 0.73). CONCLUSION: Our data show striking abnormalities in
      cardiac adrenergic nerve function and in coronary microvascular function in CSX
      patients. However, no significant relation between the two abnormalities was
      found. Further studies are needed to clarify the mechanisms and the role of MIBG
      defects in CSX patients.

PMID- 19164331
TI  - Microvascular dysfunction in patients with cardiac syndrome X.

PMID- 19164332
TI  - Cardiovascular flashlight. Paraganglioma of the aortopulmonary window.

PMID- 19164334
TI  - Tako-tsubo cardiomyopathy or aborted myocardial infarction?

PMID- 19164335
TI  - Metabolic syndrome and collateral vessel formation in patients with documented
      occluded coronary arteries: association with hyperglycaemia, insulin-resistance,
      adiponectin and plasminogen activator inhibitor-1.
AB  - AIMS: The metabolic syndrome (MS) is associated with an increased cardiovascular
      risk. Patients with the MS have endothelial dysfunction, decreased circulating
      adiponectin, and a high expression of angiogenic inhibitors such as plasminogen
      activator inhibitor-1 (PAI-1). We hypothesized that such patients, in the event
      of a coronary occlusion, might exhibit a less developed collateral circulation.
      METHODS AND RESULTS: Three hundred and eighty-seven consecutive patients with at
      least one coronary occlusion of a major coronary vessel at diagnostic angiography
      were prospectively enrolled. Collateral development was graded with validated
      angiographic methods. The MS was defined according to the ATP-III definition.
      Fasting glucose, adiponectin, insulin concentrations, and PAI-1 were measured at
      the time of angiography. MS was associated with less developed collateral vessels
      (P = 0.005). In multivariable analysis adjusting for potential confounding
      factors including the duration of coronary occlusion (P = 0.0001), fasting
      glycaemia (P = 0.0007), low adiponectin concentration (P = 0.01), insulin
      resistance (HOMA-IR; P = 0.01), high circulating PAI-1 concentration (P = 0.01),
      and hypertension (P = 0.008) were independently associated with poor coronary
      collateral vessel development. CONCLUSION: This study shows that in patients with
      coronary occlusion, collateral circulation is impaired in patients with the MS.
      This association is partly related to fasting glycaemia and to key parameters
      linked to insulin resistance.

PMID- 19164336
TI  - Refining the assessment of pulmonary regurgitation in adults after tetralogy of
      Fallot repair: should we be measuring regurgitant fraction or regurgitant volume?
AB  - AIMS: Pulmonary regurgitation (PR) is an important determinant of outcome after
      tetralogy of Fallot (TOF) repair. The physiologic impact of PR on the right
      ventricle remains incompletely understood. We hypothesized that a volumetric
      expression of PR would be a better measure of ventricular preload and a more
      accurate reflection of degree of insufficiency. METHODS AND RESULTS: Patients (n
      = 64) with magnetic resonance imaging after TOF repair were identified. PR was
      quantified using: (i) phase contrast (PC) analysis of main pulmonary artery flow
      and (ii) differential right and left ventricular stroke volumes. PR was expressed
      as a volume (PR(volume)) and percentage of total forward flow (PR(fraction)). The
      median PC(PR volume) was 19 mL/m(2) (range 0-63 mL/m(2)) and PC(PR fraction) was
      29% (range 0-58%). PR(fraction) was found to be highly variable in terms of
      absolute PR(volume). In those with significant PR, PR(volume) was better than
      PR(fraction) for the identification of severe RV dilation (receiver-operator
      curve area: 0.83 vs. 0.71, P = 0.003). PR(volume) using PC analysis was better at
      differentiating moderate from severe RV dilation (P = 0.005) as compared with
      PR(fraction) (P = 0.064). CONCLUSION: PR(volume) and PR(fraction) are not
      interchangeable. PR(volume) may be a more accurate reflection of RV preload and
      may better represent physiologically significant PR as compared with
      PR(fraction).

PMID- 19164337
TI  - Serum insulin-like growth factor binding protein-1: an improvement over other
      simple indices of insulin sensitivity in the assessment of subjects with normal
      glucose tolerance.
AB  - BACKGROUND: Insulin resistance is associated with an increased risk of
      cardiovascular disease and diabetes. It can be assessed using complex reference
      techniques, such as clamp or frequently sampled intravenous glucose tolerance
      test (FSIVGTT). Therefore, simple indices derived from fasting insulin and
      glucose concentrations have been proposed. The aim of this study is to assess
      fasting serum insulin-like growth factor binding protein-1 (IGFBP-1) as a simple
      index of insulin sensitivity compared with other simple indices and FSIVGTT.
      METHODS: Fasting serum IGFBP-1, fasting plasma insulin (FPI), homeostasis model
      assessment (HOMA-IR), quantitative insulin check index (QUICKI), fasting glucose
      to insulin ratio (FGIR), Raynaud and insulin glycaemic index (ISI-gly) were
      correlated with FSIVGTT (Si) in 22 subjects with normal glucose tolerance (NGT)
      and nine with impaired fasting glucose (IFG). RESULTS: In NGT individuals, IGFBP
      1 correlated more strongly with Si than did any other index both before (r =
      0.76) and after (r = 0.79) natural logarithm (ln) transformation. In subjects
      with IFG, IGFBP-1 was weakly correlated with Si before and after ln
      transformation (r = 0.55, r = 0.56, respectively), but ISI-gly was the index most
      strongly correlated with Si (r = 0.77, r = 0.85, respectively). CONCLUSIONS: In
      subjects with NGT, fasting serum IGFBP-1 could be used as a simple reliable
      marker of insulin sensitivity. For more accurate estimation of insulin
      sensitivity in normal subjects and those with IFG, ln-transformation is preferred
      over raw data.

PMID- 19164338
TI  - Novel automated pulse immunoassay for human alpha-fetoprotein.
AB  - BACKGROUND: To improve current alpha-fetoprotein (AFP) assays, which are
      expensive and time-consuming, a specific AFP reagent has been developed for
      practical use in our newly developed high-speed, highly sensitive pulse
      immunoassay (PIA) system, in which a latex immunoagglutination reaction is
      carried out under a high-frequency pulse voltage, leading to an enhanced
      immunological reaction. METHODS: We evaluated the assay performance
      (reproducibility, sensitivity, dilution linearity, interference) of the newly
      developed automated AFP PIA compared with the current AFP assay. RESULTS: Using
      pooled serum samples, the within-run reproducibility resulted in a correlation
      variation of 3.6-4.7%. The AFP assay detection limit was determined to be 2.5
      microg/L. Linear sequential dilution was found up to nearly 700 microg/L. Even up
      to an AFP concentration of 1.0 g/L, the prozone phenomenon was not observed. Free
      and conjugated bilirubin, haemolytic haemoglobin, chyle and rheumatoid factor did
      not show any test interference. Using AFP-positive serum samples from 114
      patients, the correlation between our PIA and a chemiluminescence immunoassay
      resulted in an excellent correlation coefficient of 0.994. CONCLUSIONS: The
      performance of AFP reagents in the PIA device shows that the system has excellent
      speed and equal sensitivity and specificity compared with the most highly
      sensitive conventional method. Our PIA system thus appears ready for use in the
      clinical diagnosis setting.

PMID- 19164339
TI  - The upper limit of the reference range for thyroid-stimulating hormone should not
      be confused with a cut-off to define subclinical hypothyroidism.
AB  - The upper limit of the reference range for serum thyroid-stimulating hormone
      (TSH) is used to assist in identifying individuals with hypothyroidism.
      Improvements in TSH assays have led to better definition of the lower limit of
      the reference range, but the upper limit of the range for a healthy population is
      currently a topic of some debate. Population studies have improved our
      understanding of the clinical implications of elevated serum TSH concentrations
      in terms of future progression to hypothyroidism, but have not yet fully
      elucidated the correlation of modestly elevated TSH levels with long-term
      morbidity. This paper will review the current debate including the arguments for
      and against reducing the upper limit of the TSH range, whether such a level
      should be based on evidence from epidemiological studies, and the implications of
      categorizing large numbers of people with subclinical hypothyroidism. The impact
      of using different methodologies for the measurement of TSH and the inherent
      variability of results on reference ranges is also discussed. We argue that the
      reference range for TSH should be assay-specific and be determined by standard
      techniques in normal populations as recommended by the National Academy of
      Clinical Biochemistry. In contrast, we suggest that a decision level be
      determined separately from epidemiological studies to identify a population with
      subclinical hypothyroidism. Serial monitoring of TSH in this population deserves
      further study as a means of identifying those at risk of progressing to frank
      hypothyroidism and meriting treatment.

PMID- 19164340
TI  - Evaluation of the particle gel diffusion technique for the detection of
      haemoglobin S in Sudanese patients.
AB  - BACKGROUND: Sickle cell disease is a heterogenous disorder characterized by an
      abnormal haemoglobin and sickling phenomena of red cells. It is prevalent among
      certain nomadic tribes in Sudan. Painful, aplastic and haemolytic crises mark
      sickle cell anaemia. Haemoglobin S (HbS) is detected using haemoglobin
      electrophoresis, iso-electric focusing and/or high-performance liquid
      chromatography techniques with high sensitivity, but entails cost and expertise.
      This study aimed to determine the sensitivity, specificity and positive
      predictive values (PPV) of the ID-particle gel diffusion technique for screening,
      diagnosis and phenotyping of HbS in patients with a provisional diagnosis of
      abnormal haemoglobin. METHODS: Following informed consent, 100 sequential
      individuals who reported to a central referral haemoglobinopathy clinic were
      enrolled. ID-particle gel diffusion technique was compared with cellulose acetate
      electrophoresis to determine haemoglobin phenotypes. RESULTS: The ID-particle gel
      test detected HbAA with 100% sensitivity and 100% specificity. Sensitivity for
      HbS was 100%, whether as HbSS or as a mixed pattern. HbSS was identified in all
      cases where this is the only haemoglobin present. Other patterns were detected
      with <100% specificity and these would require further testing by other means to
      definitively identify abnormal haemoglobins. CONCLUSIONS: Although the ID
      particle technique is a simple and cheap technique with high sensitivity,
      specificity and PPV compared with cellulose acetate electrophoresis in detecting
      HbSS, it could not differentiate HbAS from HbSS with high levels of HbF. High
      environmental temperatures could melt the test microtubes. Cellulose acetate
      electrophoresis remains the technique of choice for the screening of abnormal
      haemoglobins in the Sudan.

PMID- 19164341
TI  - The rise and fall of C-reactive protein: managing demand within clinical
      biochemistry.
AB  - BACKGROUND: Managing workload within the laboratory has become a key role for
      clinical biochemists. National benchmarking data highlighted a 31% increase in C
      reactive protein (CRP) requests between 2003-2004 and 2004-2005 for the
      University Hospital of North Staffordshire (UHNS). The aim of this study was to
      examine CRP requesting patterns within the acute admissions units. METHODS:
      Current requesting patterns within the Accident and Emergency Department (A&E)
      and Medical Admissions Unit (MAU) were audited. Following discussion with
      clinical colleagues, the laboratory implemented agreed disease-related protocols
      and consultant only requesting. The impact these demand management strategies had
      on requesting within these units was then assessed. RESULTS: The initial data
      (January-June 2005) showed that the average number of requests for CRP was 918
      per month from A&E and 545 per month for MAU. Implementation of demand-management
      strategies resulted in an overall reduction of 85% in the numbers of requests,
      saving the Trust approximately pound10,000 per annum. Further to the initial
      protocols, an IT-based logic rule was also developed to reduce CRP requests made
      within a 24 h time window of an initial request and educate users. CONCLUSION:
      This study has demonstrated that strategies to control demand at the requesting
      stage have been able to reduce the number of requests from acute admission units.
      This study forms the basis for ongoing work on inappropriate requesting and
      illustrates that the introduction of agreed protocols in acute settings can be
      used as a demand-management tool.

PMID- 19164342
TI  - Thiopurine S-methyltransferase genotype-phenotype concordance: used as a quality
      assurance tool to help control the phenotype assay.
AB  - BACKGROUND: As part of the quality control system for our TPMT phenotyping
      service we monitor the genotype-phenotype concordance for patient samples with
      deficient and low TPMT activity. We have studied the genotype-phenotype
      concordance over the last year to demonstrate its effectiveness as a quality
      assurance tool. METHODS: From July 2007 to July 2008 TPMT genotyping was
      performed on all routine samples analysed using our phenotypic assay with an
      activity of <or=40 nmol 6-MTG/gHb/h. The monthly genotype-phenotype concordance
      was calculated between: all deficient TPMT activity results and a homozygous
      mutant or compound heterozygote genotype, low TPMT activity and a heterozygote
      genotype, normal TPMT activity and a wild-type genotype. RESULTS: A total of
      14,832 samples were analysed by TPMT phenotyping and 1769 of these by genotyping.
      The monthly mean concordance between low TPMT activity and a mutant heterozygote
      genotype was 83%, ranging from 67-90%. The number of individuals with deficient
      TPMT activity identified by phenotyping was 44. For two of these individuals only
      one mutant allele was detected, and for one no common mutations were identified.
      CONCLUSIONS: Monitoring the genotype-phenotype concordance is an effective
      quality assurance tool for the TPMT phenotyping assay. As demonstrated in this
      study current genotyping assays risk missing some deficient patients.

PMID- 19164343
TI  - Single-dose desloratadine and montelukast and allergen-induced late airway
      responses.
AB  - Montelukast and desloratadine synergistically inhibit the allergen-induced early
      asthmatic response. Montelukast also suppresses the allergen-induced late
      asthmatic response, but there are no reports on the effect of desloratadine or
      the combination on the allergen-induced late asthmatic response. Atopic
      asthmatics (n = 10) completed a multicentric randomised double-blind crossover
      study comparing single-dose placebo, 5 mg desloratadine, 10 mg montelukast and
      the combination administered 2 h prior to allergen inhalation challenge.
      Methacholine challenges were performed 24 h before and after allergen challenge.
      Exhaled nitric oxide measurements and sputum inflammatory cell counts were also
      carried out. All active treatments significantly decreased the late asthmatic
      response area under the curve. Combination therapy provided the greatest
      inhibition compared to desloratadine and montelukast. Montelukast was
      nonsignificantly better than desloratadine but not as effective as the
      combination. There was a trend towards a decrease in airway responsiveness
      following montelukast and combination. Montelukast, but not desloratadine or the
      combination, decreased exhaled NO levels 24 h after allergen. The allergen
      induced increase in sputum eosinophil numbers was significantly suppressed at 7 h
      with desloratadine and combination therapy, and at 24 h with montelukast and
      combination therapy. Single-dose co-administration of desloratadine and
      montelukast 2 h prior to allergen inhalation clinically abolished the late
      asthmatic response and eosinophil recruitment.

PMID- 19164345
TI  - Predictors of poor treatment outcome in multi- and extensively drug-resistant
      pulmonary TB.
AB  - Treatment outcome in multidrug-resistant (MDR) and extensively drug-resistant
      (XDR) tuberculosis (TB) is often unsuccessful, but the particular determinants of
      poor treatment outcome have remained obscure. The present authors therefore
      analysed treatment effectiveness and predictors of poor treatment outcome in
      pulmonary MDR-TB and XDR-TB in Estonia, a European country with one of the
      highest MDR-TB and XDR-TB rates in the world. All culture-confirmed pulmonary MDR
      TB and XDR-TB patients who started TB treatment in 2003-2005 were included.
      Multivariate analysis was performed on two models of predictors: 1) patients' HIV
      status, demographic and socioeconomic characteristics; and 2) TB-related data. In
      the 235 MDR-TB patients, the proportion of overall successful treatment outcome
      was 60.4%, rising to 72.8% among adherent patients. Among the 54 XDR-TB patients,
      these proportions were 42.6% and 50.0%, respectively. Risk factors for poor
      treatment outcome in MDR-TB were HIV infection, previous TB treatment, resistance
      to ofloxacin and positive acid-fast bacilli (AFB) smear at the start of
      treatment. Predictors of poor treatment outcome in XDR-TB were urban residence
      and positive AFB smear. This country-wide study provides evidence that to improve
      treatment outcome in multidrug-resistant and extensively drug-resistant
      tuberculosis, special care should be taken to treat HIV-infected patients and
      urban residents, as well as to make efforts to diminish re-treatment cases by
      increasing patient adherence.

PMID- 19164344
TI  - Serum surfactant protein D is steroid sensitive and associated with exacerbations
      of COPD.
AB  - Surfactant protein (SP)-D is a lung-derived protein that has been proposed as a
      biomarker for inflammatory lung disease. Serum SP-D was evaluated as a biomarker
      for components of chronic obstructive pulmonary disease (COPD) in the Evaluation
      of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE)
      cohort and its response assessed to the administration of the anti-inflammatory
      agent prednisolone. The median level of serum SP-D was significantly elevated in
      1,888 individuals with COPD compared to 296 current and former smokers without
      airflow obstruction (121.1 and 114.3 ng x mL(-1), respectively; p = 0.021) and
      201 nonsmokers (82.2 ng x ml(-1); p<0.001). There was no correlation with the
      severity of COPD. Individuals with COPD who had a serum SP-D concentration that
      was greater than the 95th percentile of nonsmokers (175.4 ng x mL(-1)) showed an
      increased risk of exacerbations over the following 12 months (adjusted OR 1.30;
      95% CI 1.03-1.63). Treatment with 20 mg x day(-1) prednisolone for 4 weeks
      resulted in a fall in serum SP-D levels (126.0 to 82.1 ng x mL(-1); p<0.001) but
      no significant change in post-bronchodilator forced expiratory volume in 1 s.
      Serum SP-D concentration is raised in smokers and may be useful in identifying
      individuals who are at increased risk of exacerbations of COPD. It may represent
      an intermediate measure for the development of novel anti-inflammatory agents.

PMID- 19164346
TI  - Exhaled nitric oxide as a marker of asthma control in smoking patients.
AB  - Exhaled nitric oxide fraction (F(eNO)), which is a reliable marker of
      eosinophilic airway inflammation, is partially suppressed by tobacco smoking.
      Consequently, its potential as a biomarker in asthma management has never been
      evaluated in smoking patients. In the present study, the authors tested the
      validity of F(eNO) to predict asthma control in this population. F(eNO) and the
      Asthma Control Questionnaire (ACQ) were recorded at least once in 411 nonsmoking
      (345 with at least two visits) and 59 smoking (51 with at least two visits)
      asthma patients. Despite similar mean ACQ scores (1.5 versus 1.7), F(eNO) was
      reduced in smoking asthmatics (18.1 ppb versus 33.7 ppb). A decrease in F(eNO) of
      <20% precludes asthma control improvement in nonsmoking (negative predictive
      value (NPV) 78%) and in smoking patients (NPV 72%). An increase in F(eNO) <30% is
      unlikely to be associated with deterioration in asthma control in both groups of
      patients (NPV = 86% and 84% in nonsmoking and smoking patients, respectively). It
      is concluded that, even in smokers, sequential changes in F(eNO) have a
      relationship with asthma control. The present study is the first to indicate that
      cigarette smoking does not obviate the clinical value of measuring F(eNO) in
      asthma among smokers.

PMID- 19164347
TI  - Effect of bronchodilation on expiratory flow limitation and resting lung
      mechanics in COPD.
AB  - Bronchodilator drugs produce variable improvements in forced expiratory volume in
      1 s (FEV(1)), but larger changes in end-expiratory lung volume (EELV) in chronic
      obstructive pulmonary disease (COPD), which were suggested to be related to the
      presence of expiratory flow limitation (EFL) at rest. We tested this concept in
      42 COPD patients (FEV(1) 42.3+/-13.8% predicted) during spontaneous breathing
      before and after 5 mg nebulised salbutamol. EFL was detected by within-breath
      changes in respiratory system reactance measured by a multifrequency forced
      oscillation method, while changes in EELV were assessed by inspiratory capacity
      (IC). Bronchodilation (BD) increased IC (from 1.8+/-0.5 to 2.1+/-0.6 L, p<0.001)
      and reduced inspiration resistance ((insp)) at 5 Hz (from 5.1+/-1.6 to 4.2+/-1.5
      cmH(2)OxsxL(-1), p<0.001). (insp) identified BD responders with a discriminative
      power of 80.1%. In total, 20 patients were flow-limited before BD. They showed
      worse spirometry and higher residual volume, but significant improvements in IC
      were seen in all patients irrespective of flow limitation. Changes in (insp) were
      confined to flow-limited patients, as were reactance changes. BD reduced the
      degree of heterogeneity in the respiratory system, a change best seen with
      inspiratory values. BD has complex effects on lung mechanics in COPD, and EFL
      affects both this and the response of some respiratory variables to treatment.
      However, changes in EELV are consistently seen, irrespective of the presence of
      flow limitation at rest.

PMID- 19164348
TI  - FcepsilonRI-mediated thymic stromal lymphopoietin production by interleukin-4
      primed human mast cells.
AB  - A significant increase of mRNA expression of thymic stromal lymphopoietin (TSLP)
      has been reported in the bronchial mast cells (MCs) of asthmatic subjects;
      however, the mechanism underlying the upregulation of TSLP mRNA and protein
      remains unknown. FcepsilonRI-mediated activation of human MCs upregulated TSLP
      mRNA expression by 5.2+/-2.9-fold, while activation of the MCs using
      lipopolysaccharide and polyriboinosinic:polyribocytidylic acid failed to
      upregulate TSLP. Stimulation of MCs with interleukin (IL)-4 alone did not affect
      the TSLP mRNA expression, while pre-incubation of MCs with IL-4 for 48 h
      significantly enhanced the FcepsilonRI-mediated TSLP mRNA expression (by 53.7+/
      15.9-fold; p<0.05) and the amount of TSLP in the cell pellets increased
      significantly from 23.4+/-4.3 pg mL(-1) to 121.5+/-3.7 pg mL(-1) (p<0.0001).
      However, the released TSLP was rapidly degraded by proteases that were released
      by MCs. We identified the population of cells expressing TSLP in the lungs of 16
      asthmatic and 11 control subjects by immunohistochemistry. The percentage of TSLP
      positive MCs in the total population of MCs was significantly increased in
      asthmatic airways (p<0.0001). Thus, MCs are able to store TSLP intracellularly
      and to produce TSLP following aggregation of FcepsilonRI in the presence of IL-4.

PMID- 19164349
TI  - Effect of heliox breathing on flow limitation in chronic heart failure patients.
AB  - Patients with chronic heart failure (CHF) exhibit orthopnoea and tidal expiratory
      flow limitation in the supine position. It is not known whether the flow-limiting
      segment occurs in the peripheral or central part of the tracheobronchial tree.
      The location of the flow-limiting segment can be inferred from the effects of
      heliox (80% helium/20% oxygen) administration. If maximal expiratory flow
      increases with this low-density mixture, the choke point should be located in the
      central airways, where the wave-speed mechanism dominates. If the choke point
      were located in the peripheral airways, where maximal flow is limited by a
      viscous mechanism, heliox should have no effect on flow limitation and dynamic
      hyperinflation. Tidal expiratory flow limitation, dynamic hyperinflation and
      breathing pattern were assessed in 14 stable CHF patients during air and heliox
      breathing at rest in the sitting and supine position. No patient was flow-limited
      in the sitting position. In the supine posture, eight patients exhibited tidal
      expiratory flow limitation on air. Heliox had no effect on flow limitation and
      dynamic hyperinflation and only minor effects on the breathing pattern. The lack
      of density dependence of maximal expiratory flow implies that, in CHF patients,
      the choke point is located in the peripheral airways.

PMID- 19164350
TI  - Quality of life measured by the St George's Respiratory Questionnaire and
      spirometry.
AB  - The present authors aimed to determine if the criteria for the diagnosis of
      chronic obstructive pulmonary disease (COPD) and its classification by severity
      as recommended by the Global Initiative for Chronic Obstructive Lung Disease are
      supported by measurements of respiratory health-related quality of life. A
      community-based sample of adults aged 25-75 yrs had pre- and post-bronchodilator
      spirometry and completed the St George's Respiratory Questionnaire (SGRQ). Loess
      scatter plot smoothers of the SGRQ versus post-bronchodilator forced expiratory
      volume in one second (FEV(1))/forced vital capacity (FVC) ratio and post
      bronchodilator FEV(1) % predicted together with receiver operating characteristic
      (ROC) curve analysis were used to determine the relationship between spirometric
      variables and clinically important differences in the SGRQ score. The scatter
      plot smoother and ROC curve analyses supported the value of 0.7 for post
      bronchodilator FEV(1)/FVC ratio, which was approximately 4 units higher than the
      nadir of the SGRQ. To represent a distance of 8 units on the SGRQ, the cut-off
      points for post-bronchodilator FEV(1) that delimit COPD severity stages were 80,
      60 and 40% pred for mild, moderate and severe COPD, respectively. To diagnose
      chronic obstructive pulmonary disease the use of post-bronchodilator forced
      expiratory volume in one second/forced vital capacity ratio of 0.7 is supported
      by health-related quality of life measurements. There may be advantages in using
      forced expiratory volume in one second cut-off points of 80, 60 and 40% predicted
      for the classification of mild, moderate and severe chronic obstructive pulmonary
      disease, respectively, similar to the approach recommended for asthma.

PMID- 19164351
TI  - Sex differences in emphysema phenotype in smokers without airflow obstruction.
AB  - Data on sex differences in emphysema are limited to chronic obstructive pulmonary
      disease. We aimed to verify whether such differences also exist in smokers
      without airflow obstruction, weighting their influence on the relationship
      between emphysema and clinical features. We evaluated both clinical and
      multidetector computed tomography (MDCT) data of 1,011 heavy smokers recruited by
      a lung cancer screening project. MDCT scans were analysed with software allowing
      lobar quantification of emphysema features. For these measures, multiple
      regression models were applied to assess the effect of patients sex, after
      allowance for age, body mass index (BMI), smoking history, forced expiratory
      volume in 1 s (FEV(1)) and forced vital capacity. The final study cohort
      consisted of 957 smokers without airflow obstruction. Compared with males,
      females exhibited an emphysema phenotype less extensive in each pulmonary lobe,
      characterised by smaller emphysematous areas and less concentrated in the core of
      the lung. However, in females, the increase of emphysema with age was more
      pronounced and displayed a more significant relationship with FEV(1)% decline;
      conversely, in males there was a stronger association with the decrease in BMI.
      Males and females respond differently to the type and location of lung damage due
      to tobacco exposure. In smokers, sex influences the relationship between
      emphysema and clinical features.

PMID- 19164352
TI  - Role of lymphotoxin-alpha in cigarette smoke-induced inflammation and lymphoid
      neogenesis.
AB  - In chronic obstructive pulmonary disease (COPD), chronic inflammation is
      accompanied by peribronchial lymphoid aggregates. Lymphotoxin (LT)-alpha, crucial
      in secondary lymphoid organogenesis, may be involved in lymphoid neogenesis. We
      examined cigarette smoke (CS)-induced pulmonary lymphoid neogenesis and
      inflammation in vivo in LTalpha knockout (LTalpha(-/-)) and wild-type (WT) mice
      and studied the expression of lymphoid chemokines by lung fibroblasts in vitro. T
      cell numbers (in bronchoalveolar lavage fluid (BALF) and lungs) and lymphoid
      aggregate numbers were significantly higher in air-exposed LTalpha(-/-) mice than
      in WT animals, and increased upon chronic CS exposure in both genotypes. In
      contrast, local immunoglobulin A responses upon chronic CS exposure were
      attenuated in LTalpha(-/-) mice. CXC chemokine ligand (CXCL) 13 and CC chemokine
      ligand (CCL) 19 mRNA in total lung and CXCL13 protein level in BALF increased
      upon CS exposure in WT, but not in LTalpha(-/-) mice. In vitro lymphotoxin-beta
      receptor (LTbetaR) stimulation induced CXCL13 and CCL19 mRNA in WT lung
      fibroblasts. Furthermore, in vitro exposure to CS extract upregulated CXCL13 mRNA
      expression in WT, but not in LTbetaR(-/-), lung fibroblasts. In this murine model
      of COPD, CS induces pulmonary expression of lymphoid chemokines CXCL13 and CCL19
      in a LTalphabeta-LTbetaR-dependent fashion. However, LTalpha is not required for
      CS-induced pulmonary lymphocyte accumulation and neogenesis of lymphoid
      aggregates.

PMID- 19164353
TI  - Evaluation of allergic lung inflammation by computed tomography in a rat model in
      vivo.
AB  - The ability of micro-computed tomography (CT) to noninvasively evaluate allergic
      pulmonary inflammation in an experimental model was investigated. In addition,
      two image segmentation methods and the value of respiratory gating were
      investigated in the context of this model. Brown Norway rats were exposed to one
      of four doses of house dust mite (HDM) extract (0, 0.15, 15 or 150 microg)
      delivered intratracheally every 24 h for 10 days. CT scanning was performed at
      baseline and after several longitudinal HDM exposures. Both thoracic- and lung
      segmentation methods yielded similar results when standardisation practices were
      employed. While tissue histology correlated well with CT images, cell counts from
      bronchoalveolar lavage depicted greater inflammation than did density measures
      from CT images. Evidence from representative CT slices and transaxial density
      distribution indicated that inflammation was primarily associated with major
      airways and extended into the periphery from these focal points. Respiratory
      gating demonstrated that images of the inspiratory state provided greater
      contrast of inflammatory processes. Lastly, decreases in tidal volumes indicated
      significant mechanical respiratory changes in animals exposed to both 15 and 150
      microg. In summary, CT image segmentation can extract pertinent data on in vivo
      allergic airway/lung inflammation. Furthermore, respiratory gating provides
      additional contrast and insight into these quantification practices.

PMID- 19164354
TI  - Validation of the COPD severity score for use in primary care: the NEREA study.
AB  - Spirometry is underused for the assessment of severity of chronic obstructive
      pulmonary disease (COPD) in primary care (PC). Therefore, simple assessment tools
      are required in this setting. The aim of the present study was to validate the
      COPD severity score (COPDSS) for use in PC. A multicentric study was carried out
      in stable COPD patients in PC. The concurrent validity of the COPDSS was
      evaluated by examining the association between COPDSS, COPD clinical indicators
      and the London Chest Activity of Daily Living (LCADL) scale, European quality of
      life (EuroQOL) questionnaires and Charlson comorbidity index. A total of 837
      patients with COPD were analysed (males 84.3%; mean+/-sd age 68+/-11 yrs; forced
      expiratory volume in one second 54.6+/-17.7% of the predicted value). A strong
      correlation was found between COPDSS and dyspnoea level and a moderate
      correlation between COPDSS and exacerbation number. The COPDSS discriminated
      between patients with varying degrees of dyspnoea (area under receiver operating
      characteristic (ROC) curve 0.837), and according to number of exacerbations in
      the last year (area under ROC curve 0.773). Higher COPDSS scores were
      significantly associated with lower EuroQOL scores, lower EuroQOL visual analogue
      scale scores and higher LCADL scores. The present results indicate that the
      chronic obstructive pulmonary disease severity score is a useful and reliable
      tool for assessing the severity of chronic obstructive pulmonary disease in
      primary care.

PMID- 19164355
TI  - Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of acute
      lung injury.
AB  - Fas-mediated apoptosis of the alveolar epithelium is important in the
      pathogenesis of acute respiratory distress syndrome. Erythropoietin (EPO) has
      cytoprotective properties in other organ systems, and is relatively deficient in
      critical illness. This study investigates a potential role for EPO in reducing
      apoptosis in a model of acute lung injury. Apoptosis was induced in human
      alveolar epithelial (A549) cells or normal human bronchial epithelial (NHBE)
      cells by Fas activation with CH-11 Fas-crosslinking antibody or by co-culture
      with polymorphonuclear neutrophils in a transwell system. The effect of
      recombinant human (rh)EPO on apoptosis was measured by poly(ADP-ribose)
      polymerase cleavage and cell death detection assay. The specific EPO-EPO receptor
      (EPOR)-mediated effect was determined using an EPO-blocking antibody or EPOR
      small interfering RNA. Expression of EPOR was demonstrated in A549, NHBE and
      normal human alveolar epithelium. Fas- and neutrophil-mediated apoptosis of A549
      and NHBE cells was inhibited by rhEPO by a specific EPO-EPOR-mediated mechanism.
      This anti-apoptotic effect was associated with induction of a pro-apoptotic Bcl
      xL/Bax ratio. EPO has cytoprotective properties in respiratory epithelium in an
      in vitro model, which may indicate a potential therapeutic role in acute lung
      injury.

PMID- 19164356
TI  - Effects of ciclesonide and fluticasone on cortisol secretion in patients with
      persistent asthma.
AB  - We compared the systemic and clinical effects of ciclesonide (CIC) and
      fluticasone propionate (FP) administered, in addition to CIC 160 microg x day(-1)
      and salmeterol 50 microg twice daily, in 32 patients with persistent asthma using
      a randomised double-blind, placebo-controlled, double-dummy, five-period
      crossover design. All patients exhibited a provocative concentration leading to a
      20% decrease in forced expiratory volume in 1 s (PC(20)) methacholine <8 mg x mL(
      1) and a PC(20) adenosine <60 mg x mL(-1). Primary outcome was 24-h serum
      cortisol suppression after 7 days. Secondary outcomes were changes in PC(20)
      methacholine and adenosine after 9 days. FP 500 microg x day(-1) and 1,000 microg
      x day(-1) significantly suppressed cortisol secretion versus placebo by -46.2
      (95% confidence interval (CI) -83.8- -8.5) nmol x L(-1) and by -76.1 (95% CI 
      112.9- -39.3) nmol x L(-1), respectively. Neither dose of CIC (320 nor 640 microg
      x day(-1)) had a significant suppressive effect (-28.2 (95% CI -65.5-9.2) nmol x
      L(-1) and -37.3 (95% CI -74.7-0.0) nmol x L(-1), respectively). Differences
      between FP 1,000 microg x day(-1) and both CIC treatments were statistically
      significant (CIC 320 microg x day(-1): -48.0 (95% CI -84.8- -11.1) nmol x L(-1);
      CIC 640 microg x day(-1): -38.8 (95% CI -75.7- -1.9) nmol x L(-1)). Compared with
      placebo, the increase in PC(20) adenosine after the four treatments was small,
      but significant. Greater improvements in PC(20) adenosine were seen with FP 500
      microg x day(-1) (1.8 (95% CI 1.0-2.6) doubling concentrations) compared with CIC
      320 microg x day(-1) (0.9 (95% CI 0.1-1.7) doubling concentrations). No
      significant difference was seen between CIC 640 microg x day(-1) and FP 1,000
      microg x day(-1). For a similar decrease in hyperresponsiveness, cortisol
      secretion was suppressed significantly with moderate-to-high doses of fluticasone
      propionate, but not with ciclesonide.

PMID- 19164358
TI  - Leukotriene B4 release by human lung macrophages via receptor- not voltage
      operated Ca2+ channels.
AB  - Increased numbers of macrophages and neutrophils in the lung is a key feature of
      chronic obstructive pulmonary disease (COPD). The major neutrophil chemotactic
      agent in the airways of COPD patients is leukotriene (LT)B(4) and is released by
      macrophages. The present study examines the role and mechanism of Ca(2+) in
      platelet-activating factor (PAF)-stimulated LTB(4) release from human lung
      macrophages. Macrophages were isolated from lung tissue of subjects undergoing
      lung resection surgery and monocyte-derived macrophages (MDM) were obtained from
      nonsmokers, smokers without obstruction and COPD patients. Cells were stimulated
      with PAF and LTB(4) release and [Ca(2+)](i) was measured. Lung macrophages and
      MDM released LTB(4) following stimulation with PAF (mean effective concentration:
      0.08+/-0.06 microM (n = 5) versus 0.17+/-0.12 microM (n = 17), respectively).
      Compared with MDM, lung macrophages released approximately eight-fold more
      LTB(4). Neither smoking nor COPD altered MDM responses. PAF-stimulated LTB(4)
      release was abrogated by ethylene glycol tetraacetic acid suggesting a role for
      extracellular Ca(2+). This was substantiated by using store-operated channel
      blockers econazole, SK&F96365 and Gd(3+). However, econazole and SK&F96365 were
      more effective in MDM than lung macrophages. Neither LOE908 nor nifedipine could
      attenuate this response. These data suggest that platelet-activating factor
      stimulated leukotriene B(4) release from human lung macrophages is mediated, in
      part, by Ca(2+) influx through receptor- but not voltage-operated Ca(2+)
      channels.

PMID- 19164359
TI  - Rate of progression of lung function impairment in alpha1-antitrypsin deficiency.
AB  - The aim of the present study was to identify alpha(1)-antitrypsin (alpha(1)-AT)
      deficient patients who had rapidly progressive disease. PiZ patients (n = 101)
      underwent annual lung function measurements over a 3-yr period, and the results
      were related to factors that may influence decline. The mean annual decline in
      forced expiratory volume in 1 s (FEV(1)) was 49.9 mL. The greatest FEV(1) decline
      occurred in the moderate severity group (FEV(1) 50-80% of the predicted value),
      with a mean annual decline of 90.1 mL, compared with 8.1 mL in the very severe
      group (FEV(1) <30% pred). However, annual decline in transfer coefficient of the
      lung for carbon monoxide (K(CO)) was greatest in the severe and very severe
      groups. When the whole group was divided into tertiles of FEV(1) decline, the
      fast tertile compared with the slow tertile had more patients with bronchodilator
      reversibility (BDR) (73 versus 41%; p = 0.010), more males (79 versus 56%; p =
      0.048) and lower body mass index (BMI) (24.0 versus 26.1; p = 0.042). Logistic
      regression analyses confirmed that FEV(1) decline was independently associated
      with BMI, BDR, exacerbation rate and high physical component 36-item short-form
      health survey scores. In PiZ alpha(1)-AT-deficient patients, FEV(1) decline was
      greatest in moderate disease, unlike K(CO) decline, which was greatest in severe
      disease. The FEV(1) decline showed associations with BDR, BMI, sex and
      exacerbation rate.

PMID- 19164360
TI  - Device therapy in heart failure: do all treatment goals apply to all patients?

PMID- 19164361
TI  - Implantable cardioverter defibrillator therapy for non-ischaemic cardiomyopathy.
      What is the role of programmed electrical stimulation?

PMID- 19164357
TI  - Effect of breastfeeding on asthma, lung function and bronchial hyperreactivity in
      ISAAC Phase II.
AB  - The association between breastfeeding and wheezing, lung function and atopy was
      evaluated in the International Study of Asthma and Allergy in Childhood (ISAAC)
      Phase II. Cross-sectional studies were performed in 27 centres in 20 countries.
      Information on disease and exposure factors was collected by parental
      questionnaires. Data from 54,000 randomly selected school children (aged 8-12
      yrs, 31,759 with skin prick testing) and a stratified subsample (n = 4,888) were
      used for testing the correlation of breastfeeding with bronchial hyperreactivity
      and lung function. Random effect models for meta-analysis were applied to
      calculate combined odds ratios (ORs). Any breastfeeding was associated with less
      wheeze both in affluent (adjusted OR (OR(adj)) 0.87, 95% confidence interval (CI)
      0.78-0.97) and nonaffluent countries (OR(adj) 0.80, 95% CI 0.68-0.94). Further
      analyses revealed that this was true only for nonatopic wheeze in nonaffluent
      countries (OR(adj) 0.69, 95% CI 0.53-0.90). Breastfeeding was not associated with
      atopic wheeze and objective measures of allergy in both affluent and nonaffluent
      countries. In contrast, breastfeeding was associated with higher predicted forced
      expiratory volume in one second in affluent countries only (mean ratio 1.11, 95%
      CI 1.02-1.20). Breastfeeding is associated with protection against nonatopic
      wheeze, which becomes particularly evident in nonaffluent countries. Overall,
      breastfeeding was not related to any measure of allergy. These findings may
      explain some of the controversy regarding breastfeeding, since the direction of
      the association with breastfeeding depends on the predominating wheeze phenotype
      (e.g. atopic, nonatopic).

PMID- 19164362
TI  - ST-segment depression as a risk factor in hypertrophic cardiomyopathy.
AB  - AIMS: From the spectrum of electrocardiogram (ECG) changes that may occur in
      hypertrophic cardiomyopathy (HCM), there is no criterion reported to be useful
      for risk stratification. We sought to determine whether there was a relationship
      between the resting ECG findings and prognosis in patients with HCM. METHODS AND
      RESULTS: We retrospectively analysed data on 173 consecutive patients admitted to
      our centre with a diagnosis of HCM. The 12-lead ECGs were assessed for underlying
      rhythm, PR interval, QRS voltages, QRS width, corrected QT interval, ST-segment
      deviation, T-wave inversion, and left atrial enlargement (LAE). During a mean
      follow-up of 50 months, 6.4% of patients had a combined endpoint [sudden death or
      appropriate implantable cardioverter-defibrillator (ICD) therapy]. The frequency
      of the combined endpoint was greater in patients with syncope, non-sustained
      ventricular tachycardia, maximal left ventricular (LV) wall thickness >or=30 mm,
      and ST-segment depression in the high lateral leads (all P < 0.05). Other ECG
      findings (LV hypertrophy, LAE, abnormal Q wave, abnormal ST-T changes, and
      underlying rhythm), family history of sudden death, and LV outflow obstruction
      were not related to the combined endpoint. The results of our multivariate
      analysis demonstrated that ST-segment depression in the high lateral leads (OR:
      20.0, 95% CI: 12.7-27.5; P = 0.0001) and syncope (OR: 19.0, 95% CI: 11.7-26.9; P
      = 0.0001) were the predictors of sudden death or appropriate ICD therapy in
      patients with HCM. CONCLUSION: The results of this study indicated that, in
      addition to generally accepted risk factors, ST-segment depression in the high
      lateral leads could be of prognostic significance in HCM patients.

PMID- 19164363
TI  - Requirement for coronary sinus lead interventions and effectiveness of
      endovascular replacement during long-term follow-up after implantation of a
      resynchronization device.
AB  - AIMS: The aim of this study was to assess the requirement for coronary sinus (CS)
      lead intervention after cardiac resynchronization therapy (CRT) and to evaluate
      the effectiveness of endovascular replacement. METHODS AND RESULTS: All patients
      receiving a CRT device with CS lead in the Leiden University Medical Center in
      the period from 1999 to 2007 were prospectively evaluated and followed. Five
      hundred and seventy-seven patients were successfully implanted with a CRT device.
      Nine (1.6%) patients were lost to follow-up. The remaining 568 patients were
      included in the analysis. During a median follow-up time of 645 days (inter
      quartile range, 260-1148), 7% of the patients required a CS lead intervention.
      Cause of the intervention was an elevated threshold (n = 13), loss of capture (n
      = 20), or intractable phrenic nerve stimulation (n = 6). Fifteen patients (38%)
      required a CS lead intervention before first scheduled follow-up (2 months after
      implantation). Thirteen patients (33%) warranted a CS lead intervention more than
      6 months after implantation. The first endovascular replacement was successful in
      86% (32 of 37), whereas a second endovascular approach failed in 66% (2 of 3).
      CONCLUSION: The long-term requirement for CS lead interventions is 7%.
      Endovascular repositioning or replacement is successful in the majority of cases.

PMID- 19164366
TI  - Abstracts of CardioRhythm 2009. February 20-22, 2009. Hong Kong.

PMID- 19164386
TI  - Replication and extension of genome-wide association study results for obesity in
      4923 adults from northern Sweden.
AB  - Recent genome-wide association studies (GWAS) have identified multiple risk loci
      for common obesity (FTO, MC4R, TMEM18, GNPDA2, SH2B1, KCTD15, MTCH2, NEGR1 and
      PCSK1). Here we extend those studies by examining associations with adiposity and
      type 2 diabetes in Swedish adults. The nine single nucleotide polymorphisms
      (SNPs) were genotyped in 3885 non-diabetic and 1038 diabetic individuals with
      available measures of height, weight and body mass index (BMI). Adipose mass and
      distribution were objectively assessed using dual-energy X-ray absorptiometry in
      a sub-group of non-diabetics (n = 2206). In models with adipose mass traits, BMI
      or obesity as outcomes, the most strongly associated SNP was FTO rs1121980 (P <
      0.001). Five other SNPs (SH2B1 rs7498665, MTCH2 rs4752856, MC4R rs17782313, NEGR1
      rs2815752 and GNPDA2 rs10938397) were significantly associated with obesity. To
      summarize the overall genetic burden, a weighted risk score comprising a subset
      of SNPs was constructed; those in the top quintile of the score were heavier
      (+2.6 kg) and had more total (+2.4 kg), gynoid (+191 g) and abdominal (+136 g)
      adipose tissue than those in the lowest quintile (all P < 0.001). The genetic
      burden score significantly increased diabetes risk, with those in the highest
      quintile (n = 193/594 cases/controls) being at 1.55-fold (95% CI 1.21-1.99; P <
      0.0001) greater risk of type 2 diabetes than those in the lowest quintile (n =
      130/655 cases/controls). In summary, we have statistically replicated six of the
      previously associated obese-risk loci and our results suggest that the weight
      inducing effects of these variants are explained largely by increased adipose
      accumulation.

PMID- 19164391
TI  - Vascular endothelial cell-derived endothelin-1 mediates vascular inflammation and
      neointima formation following blood flow cessation.
AB  - AIMS: Although endothelin-1 (ET-1) has been suggested to contribute to the
      pathogenesis of neointima formation and atherosclerosis, the individual roles of
      ET-1 derived from certain cell types in this disease remain unclear. In this
      study, we determined the role of vascular endothelial ET-1 on vascular
      inflammation and neointima formation using vascular endothelial ET-1-knockout [ET
      1(f/f); Tie2-Cre (+)] mice. METHODS AND RESULTS: Intimal hyperplasia was induced
      by complete ligation of the left carotid artery in 12-week-old male ET
      1(f/f);Tie2-Cre (+) mice (n = 35) and the wild-type (WT) littermates (n = 34).
      Following this intervention, neointima formation was reduced in ET-1(f/f);Tie2
      Cre (+) mice compared with the WT mice, independent of the difference in blood
      pressure. This reduction was associated with a decrease in inflammatory cell
      recruitment to the vessel wall, which was accompanied by reduced expression
      levels of endothelial adhesion molecules as well as chemokines and a decrease in
      vascular smooth muscle cell proliferation. CONCLUSION: The results of our study
      provide direct evidence for the role of vascular endothelial ET-1 in mediating
      vascular inflammation and neointima formation following vascular injury in
      addition to promoting vasoconstriction and cell proliferation. Furthermore, this
      study suggests a strategy for the efficient design of ET receptor antagonists
      with targeted inhibition of ET-1 signalling in vascular endothelial cells.

PMID- 19164392
TI  - Abuse of people with dementia by family carers: representative cross sectional
      survey.
AB  - OBJECTIVE: To determine the prevalence of abusive behaviours by family carers of
      people with dementia. DESIGN: Representative cross sectional survey SETTING:
      Community mental health teams in Essex and London. PARTICIPANTS: 220 family
      carers of people newly referred to secondary psychiatric services with dementia
      who were living at home. MAIN OUTCOME MEASURE: Psychological and physical abuse
      (revised modified conflict tactics scale). RESULTS: 115 (52%, 95% confidence
      interval 46% to 59%) carers reported some abusive behaviour and 74 (34%, 27% to
      40%) reported important levels of abuse. Verbal abuse was most commonly reported.
      Only three (1.4%) carers reported occasional physical abuse. CONCLUSIONS: Abusive
      behaviour by family carers towards people with dementia is common, with a third
      reporting important levels of abuse and half some abusive behaviour. We found few
      cases of physical or frequent abuse, although those with the most abusive
      behaviour may have been reluctant to report it.

PMID- 19164394
TI  - High doses of deferiprone may be associated with cerebellar syndrome.

PMID- 19164393
TI  - Effectiveness of acute geriatric units on functional decline, living at home, and
      case fatality among older patients admitted to hospital for acute medical
      disorders: meta-analysis.
AB  - OBJECTIVE: To assess the effectiveness of acute geriatric units compared with
      conventional care units in adults aged 65 or more admitted to hospital for acute
      medical disorders. DESIGN: Systematic review and meta-analysis. DATA SOURCES:
      Medline, Embase, and the Cochrane Library up to 31 August 2008, and references
      from published literature. Review methods Randomised trials, non-randomised
      trials, and case-control studies were included. Exclusions were studies based on
      administrative databases, those that assessed care for a single disorder, those
      that evaluated acute and subacute care units, and those in which patients were
      admitted to the acute geriatric unit after three or more days of being admitted
      to hospital. Two investigators independently selected the studies and extracted
      the data. RESULTS: 11 studies were included of which five were randomised trials,
      four non-randomised trials, and two case-control studies. The randomised trials
      showed that compared with older people admitted to conventional care units those
      admitted to acute geriatric units had a lower risk of functional decline at
      discharge (combined odds ratio 0.82, 95% confidence interval 0.68 to 0.99) and
      were more likely to live at home after discharge (1.30, 1.11 to 1.52), with no
      differences in case fatality (0.83, 0.60 to 1.14). The global analysis of all
      studies, including non-randomised trials, showed similar results. CONCLUSIONS:
      Care of people aged 65 or more with acute medical disorders in acute geriatric
      units produces a functional benefit compared with conventional hospital care, and
      increases the likelihood of living at home after discharge.

PMID- 19164395
TI  - Rationing new medicines in the UK.

PMID- 19164396
TI  - Study on stem cells for stroke patients to start in Scotland later in 2009.

PMID- 19164398
TI  - Clinical evaluation of a non-immersive virtual environment in stroke
      rehabilitation.
AB  - BACKGROUND AND PURPOSE: We describe our attempts to evaluate the effectiveness of
      a virtual environment developed to rehabilitate stroke patients in the task of
      making a hot drink. METHODS: Single case studies were performed in 13/138 (9%)
      stroke patients undergoing rehabilitation in a UK stroke unit. Participants in
      AB/BA (n = 5) and ABA (n = 2) design studies received 5 one-hour sessions of
      attention control training (A phase) and 5 one-hour sessions of virtual
      environment training (B phase). An AB design with random duration of A and B
      phases (minimum duration of A and B phases 3 and 5 days respectively, with total
      duration of 3 weeks) was used in 6 participants. RESULTS: Visual inspection of
      scores across all cases showed a trend towards improvement over time in both real
      and virtual hot drink making ability in both control and intervention phases.
      There was no significant difference (Wilcoxon, p > 0.05) in the improvements in
      real and virtual hot drink making ability during all control and intervention
      phases in the 13 cases. Ceiling effects limited the evaluation of effectiveness
      in 5 of the 8 cases in which daily performance measures were used. CONCLUSIONS:
      Few people in this setting were suitable for this intervention. The case studies
      showed no evidence of a strong effect of this intervention, but we had great
      difficulty in performing single case studies. We conclude that more testing and
      development of this system is required before it is subjected to rigorous testing
      of clinical effectiveness.

PMID- 19164399
TI  - Efficacy of pneumatic compression and low-level laser therapy in the treatment of
      postmastectomy lymphoedema: a randomized controlled trial.
AB  - OBJECTIVE: To compare the long-term efficacy of pneumatic compression and low
      level laser therapies in the management of postmastectomy lymphoedema. DESIGN:
      Randomized controlled trial. SETTING: Department of Physical Medicine and
      Rehabilitation of Cukurova University, Turkey. SUBJECTS: Forty-seven patients
      with postmastectomy lymphoedema were enrolled in the study. INTERVENTIONS:
      Patients were randomly allocated to pneumatic compression (group I, n=24) and low
      level laser (group II, n=23) groups. Group I received 2 hours of compression
      therapy and group II received 20 minutes of laser therapy for four weeks. All
      patients were advised to perform daily limb exercises. MAIN MEASURES: Demographic
      features, difference between sum of the circumferences of affected and unaffected
      limbs (delta C), pain with visual analogue scale and grip strength were recorded.
      RESULTS: Mean age of the patients was 48.3 (10.4) years. Delta C decreased
      significantly at one, three and six months within both groups, and the decrease
      was still significant at month 12 only in group II (P = 0.004). Improvement of
      group II was greater than that of group I post treatment (P = 0.04) and at month
      12 after 12 months (P = 0.02). Pain was significantly reduced in group I only at
      posttreatment evaluation, whereas in group II it was significant post treatment
      and at follow-up visits. No significant difference was detected in pain scores
      between the two groups. Grip strength was improved in both groups, but the
      differences between groups were not significant. CONCLUSIONS: Patients in both
      groups improved after the interventions. Group II had better long-term results
      than group I. Low-level laser might be a useful modality in the treatment of
      postmastectomy lymphoedema.

PMID- 19164400
TI  - Effects of pulmonary rehabilitation on fatigue, functional status and health
      perceptions in patients with chronic obstructive pulmonary disease: a randomized
      controlled trial.
AB  - OBJECTIVE: To test the effects of pulmonary rehabilitation on fatigue, functional
      status and health perceptions in patients with chronic obstructive pulmonary
      disease. DESIGN: Randomized controlled trial. SETTING: Pulmonary outpatient
      department. SUBJECTS: Thirty patients randomly assigned to a rehabilitation (3
      men, 9 women, mean age 66 (+/-2) years) or a control group (10 men, 4 women, mean
      age 64 (+/-2) years). INTERVENTIONS: The patients in the rehabilitation group
      participated in a multidisciplinary rehabilitation programme comprising exercise
      training twice weekly, for a 12-week period, nutritional and self-care advice,
      and education about disease and energy conservation strategies. MAIN MEASURES:
      Fatigue, functional limitations due to fatigue, functional performance and
      satisfaction, six-minute walking distance, hand grip strength and health
      perception were assessed at baseline and after 12 weeks. RESULTS: At baseline
      there were no significant differences between the groups, except for gender. The
      six-minute walking distance was 312.6 (+/-79.3) m for the rehabilitation group
      and 360.3 (+/-84.7) m for the control group. After 12 weeks, the rehabilitation
      group improved their walking distance by 40.6 (+/-27.2) m (P<0.05). The
      rehabilitation group improved in performance (from 4.8 (+/-2.0) to 6.0 (+/-1.5)
      scores, P<0.01) and satisfaction (from 4.6 (+/-2.2) to 6.0 (+/-2.1) scores,
      P<0.001) with regard to own selected daily activities. No statistically
      significant differences were seen between the changes within the rehabilitation
      group and changes within the control group at the 12-week follow-up. CONCLUSIONS:
      Although the pulmonary rehabilitation programme had an immediate effect, it was
      not sustained.

PMID- 19164401
TI  - Mental techniques during manual stretching in spasticity--a pilot randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the feasibility and effects of using motor imagery during
      therapeutic stretching in individuals with spasticity. DESIGN: Randomized single
      blind controlled pilot trial. SETTING: Chronic day care unit, neurological
      rehabilitation unit and in the community. SUBJECTS: Eleven individuals with
      spasticity in the arm requiring stretching as part of their normal routine.
      INTERVENTIONS: In addition to their normal stretching routine, subjects in the
      experimental group received motor imagery during their stretches (n = 6). The
      control group received progressive muscle relaxation during their stretches (n =
      5). The dose varied between 8 and 56 sessions over eight weeks. MAIN MEASURES:
      Resistance to passive movement, measured with a torque transducer, passive range
      of movement, measured with an electro-goniometer, Modified Ashworth Scale (MAS)
      and level of discomfort during the MAS were assessed at baseline and after eight
      weeks by an independent assessor. These measures were recorded before and after a
      stretch intervention on both assessments. RESULTS: Participants, therapists and
      carers tolerated the techniques well. Compliance was variable and adherence was
      good. Mixed ANOVA showed no difference over time and no difference between the
      motor imagery and progressive muscle relaxation group on the primary and
      secondary outcome measures (P>0.05). CONCLUSIONS: It is feasible to use motor
      imagery during therapeutic stretching. Statistical power was low due to the large
      variability in the population and the small sample size. Post-hoc sample size
      calculation suggests that future studies of this subject should include at least
      54 participants per group. Further research is warranted.

PMID- 19164402
TI  - An exploratory cluster randomized controlled trial of group exercise on mobility
      and depression in care home residents.
AB  - OBJECTIVE: To investigate the feasibility, acceptability and potential efficacy
      of group exercise for residents in care homes. DESIGN: Exploratory cluster
      randomized controlled trial. SETTING: Five randomly selected care homes in South
      Birmingham, UK. PARTICIPANTS: Fifty-six care home residents (mean age 84.5, 71%
      female), 39 (70%) with cognitive impairments. INTERVENTION: Two homes (n = 28)
      were randomized to group exercise held twice weekly for five weeks. The remaining
      three homes (n = 28) formed the control group and received usual care, with no
      person specifically responsible for exercise training. OUTCOME MEASURES:
      Assessments were conducted at zero (pre-intervention), three (post-intervention)
      and six months (follow-up) using the Rivermead Mobility Index and Hospital
      Anxiety and Depression Scale or Stroke Aphasic Depression Questionnaire
      (depending on cognitive impairment). Adherence to group exercise and retention to
      the study were also documented. RESULTS: No statistically significant
      improvements in mobility or depression were found in favour of group exercise.
      Retention to the study was high with 46 (82%) participants completing all
      assessments. Adherence to group exercise was somewhat lower with participants
      attending a mean of 3.61 out of 8.5 prescribed sessions (42.5%). CONCLUSIONS:
      Group exercise can be delivered to care home residents with reduced mobility but
      it is not suitable for residents with severe cognitive impairment. An estimated
      sample size of 240 participants would be required to detect a clinically
      significant difference in the Rivermead Mobility Index with 90% power.

PMID- 19164403
TI  - Short-term effects of aerobic exercise on functional capacity, fatigue, and
      quality of life in patients with post-polio syndrome.
AB  - OBJECTIVE: To investigate and compare the impact of hospital and home exercise
      programmes on aerobic capacity, fatigue, and quality of life in patients with
      post-polio syndrome. DESIGN: A prospective, randomized controlled trial. SETTING:
      Department of Physical Medicine and Rehabilitation, University Hospital.
      SUBJECTS: Thirty-two patients were divided into two groups for either hospital-
      or home-based aerobic exercise programme. MAIN OUTCOME MEASURES: Patients were
      assessed before and after the rehabilitation programme, with respect to
      functional capacity (pVo2), fatigue (Fatigue Severity Scale, Fatigue Impact
      Scale) and quality of life (Nottingham Heath Profile). RESULTS: After the
      exercise programme, improvement was observed in the hospital exercise group
      compared to a pre-exercise period in all Nottingham Heath Profile scores (except
      sleep scores), pVo2, Fatigue Severity Scale and Fatigue Impact Scale (cognitive,
      physical, psychosocial, total) (P<0.05). In contrast, in the home exercise group
      a decrease was observed in pVo2 scores after the rehabilitation programme,
      compared to a pre-rehabilitation period (P<0.05). In addition, a significant
      improvement was observed in the home exercise group after the rehabilitation
      programme in all parameters excluding Fatigue Impact Scale-physical, Fatigue
      Impact Scale-psychosocial, and Nottingham Heath Profile-sleep (P<0.05). When the
      two exercise groups were compared, improvement was observed in the hospital
      exercise group compared to the home exercise group in pVo2 and Fatigue Severity
      Scale-total, Fatigue Impact Scale-physical, Fatigue Impact Scale-psychosocial,
      Fatigue Impact Scale-total, and Nottingham Heath Profile-energy scores (P<0.05).
      CONCLUSION: Fatigue and quality of life were both improved in the home and
      hospital exercise groups. An increase was also found in the functional capacity
      in the hospital exercise group. A regular exercise programme is beneficial to
      patients with post-polio syndrome.

PMID- 19164404
TI  - Pedometer step counts in individuals with neurological conditions.
AB  - OBJECTIVE: To examine the accuracy of measuring step counts using a pedometer in
      participants with neurological conditions and healthy volunteers in relation to a
      manual step count tally. SETTING: Oxford Centre for Enablement, Nuffield
      Orthopaedic Centre NHS Trust, Oxford, UK. SUBJECTS: Healthy adults (n = 13, age:
      mean 29, SD = 12) and adults with neurological conditions (n=20 stroke, n=16
      multiple sclerosis, n=5 muscular dystrophy, n=1 spinal cord injury, n=1 traumatic
      brain injury; age: mean 54, SD=13). MAIN MEASURES: Individuals walked for 2
      minutes at self-selected walking speeds (SSWS) wearing a pedometer. Healthy
      individuals were then asked to walk at slow walking speeds (SWS). Step counts
      were recorded manually and using a pedometer. RESULTS: In healthy individuals
      there was no difference between manually measured and pedometer counts during
      walking (P>0.05). In adults with neurological conditions the pedometers
      undercounted (P = 0.003); bias (random error): 27 (111); percentage variability
      30% and intraclass correlation coefficient (ICC) 0.66. In neurological adults,
      from regression analysis the relationship between error and walking speed was
      cubic, with walking speed accounting for 29% of pedometer error. Healthy
      individuals showed greater variability and undercounting at SWS bias (random
      error): 10 (31), percentage variability 8% and ICC 0.73, compared with SSWS bias
      (random error): -3 (13), percentage variability 3% and ICC 0.84. CONCLUSIONS:
      Pedometers may undercount when used for people with neurological conditions.
      There may be variability in pedometer accuracy but this was not strongly related
      to walking speed. The suitability of pedometer use for exercise monitoring should
      be individually determined.

PMID- 19164405
TI  - Risk factors for falls in stroke patients during inpatient rehabilitation.
AB  - OBJECTIVES: To assess the incidence and circumstances of falls among stroke
      patients in a rehabilitation ward, the frequency of fall-related fractures, the
      relationship between falls and rehabilitation outcomes, and risk factors for
      falls. DESIGN: Prospective observational study. SETTING: Neurological
      rehabilitation ward. PATIENTS: In total 1155 patients (56% men; mean age 61.5 +/-
      14.3 years) admitted to the neurological rehabilitation ward after a stroke.
      Median (interquartile range) time since stroke onset was 36.5 (68) days. MAIN
      MEASURES: Patients' falls were registered during hospitalization (1-74 days) and
      variables relating to the type and symptoms of stroke, current medications,
      neurological deficit (Scandinavian Stroke Scale) and disability (Barthel Index)
      were collected from medical records. RESULTS: A total of 252 falls were recorded
      for 189 (16.3%) patients and 45 patients experienced 108 repeated falls. The
      incidence rate for falls was 7.6/1000 patient-days (95% confidence interval (CI)
      6.6-8.5). Most patients fell while being transferred (33.9%) and while seated
      (21.5%), and 1.2% of falls resulted in fractures (n = 3). Increased risk of both
      first and multiple falls was strongly associated with initial Barthel score below
      15 (hazard ratio (HR) 5.2 and 4.5, respectively) and time since stroke onset > or
      = 12 weeks (HR 2.3 and 2.3, respectively). First falls were significantly
      associated with visuo-spatial neglect (HR 1.5). Repeated falls were related to
      age greater than 65 years (HR 1.4). CONCLUSIONS: Patients with severe stroke
      related disability in the early period after stroke are prone to falls during
      rehabilitation. Multiple falls are most frequent in patients over 65 years of
      age.

PMID- 19164407
TI  - Xp11.2 translocation renal carcinoma with placental metastasis: a case report.
AB  - Renal cell carcinomas with sporadic Xp11.2 translocations are uncommon
      malignancies in children and young adults associated with several different
      reciprocal translocations involving the TFE3 gene located on chromosome Xp11.2.
      Placental metastases are extremely rare, with only a handful of cases reported.
      This study reports the case of a 20-year-old woman with an Xp11.2 translocation
      renal carcinoma that metastasized to the placenta. This is the first reported
      case of a renal cell carcinoma metastatic to the placenta and highlights the
      aggressive behavior of Xp11 translocation renal cell carcinomas.

PMID- 19164408
TI  - Glomus tumor of the kidney: case report and literature review.
AB  - Glomus tumor is a benign mesenchymal neoplasm of the subcutaneous tissue of the
      distal extremities and head and neck region. Glomus tumor rarely occurs in the
      visceral organs. This study reports the sixth case of a glomus tumor arising in
      the kidney in a 62-year-old man who presented with weight loss and an incidental
      kidney lesion detected by computed tomographic scan. Radiologically, the tumor
      was difficult to differentiate from a malignant lesion and was therefore excised
      by partial nephrectomy. The tumor was challenging to diagnose by routine
      hematoxylin and eosin microscopic examination, necessitating immunohistochemical
      analysis. Immunoreactivity was demonstrated for smooth muscle actin, vimentin,
      collagen IV, and CD57, with little to no expression of neuroendocrine,
      endothelial, or epithelial markers. To date, the tumor has followed a benign
      course without evidence of local recurrence or metastasis.

PMID- 19164409
TI  - Subepithelial pelvic hematoma (Antopol--Goldman lesion) simulating renal
      neoplasm: report of a case and review of the literature.
AB  - The Antopol-Goldman lesion is a subepithelial pelvic hematoma simulating a renal
      neoplasm. We report the clinico-pathological features of a single case and a
      review of the literature. A 76-year-old man presented with flank pain and
      hematuria. Computed tomography showed a hypodense lesion of 6 cm at the left
      kidney with filling defect at pyelogram. The patient underwent nephroureterectomy
      for suspected neoplasm. Macroscopically, a mass of 6 cm was present impinging on
      the pelvi-caliceal system. Microscopically, the lesion was composed by hemorragic
      material with feature of an hematoma. A diffuse eosinophilic amorphous material
      suspicious for amyloid was observed among intra- and extraparenchymal vessels.
      The Congo-Red staining verified the presence of amyloid. The diagnosis was
      subepithelial pelvic hematoma with severe amyloidosis. Antopol-Goldman lesion
      should be kept in mind as a possible differential diagnosis of upper urinary
      tract lesion to avoid unnecessary nephrectomies. The anamnestic knowledge of
      amiloydosis may increase this diagnostic hypothesis.

PMID- 19164410
TI  - Abnormal mandibular growth and the condylar cartilage.
AB  - Deviations in the growth of the mandibular condyle can affect both the functional
      occlusion and the aesthetic appearance of the face. The reasons for these growth
      deviations are numerous and often entail complex sequences of malfunction at the
      cellular level. The aim of this review is to summarize recent progress in the
      understanding of pathological alterations occurring during childhood and
      adolescence that affect the temporomandibular joint (TMJ) and, hence, result in
      disorders of mandibular growth. Pathological conditions taken into account are
      subdivided into (1) congenital malformations with associated growth disorders,
      (2) primary growth disorders, and (3) acquired diseases or trauma with associated
      growth disorders. Among the congenital malformations, hemifacial microsomia (HFM)
      appears to be the principal syndrome entailing severe growth disturbances,
      whereas growth abnormalities occurring in conjunction with other craniofacial
      dysplasias seem far less prominent than could be anticipated based on their often
      disfiguring nature. Hemimandibular hyperplasia and elongation undoubtedly
      constitute the most obscure conditions that are associated with prominent, often
      unilateral, abnormalities of condylar, and mandibular growth. Finally,
      disturbances of mandibular growth as a result of juvenile idiopathic arthritis
      (JIA) and condylar fractures seem to be direct consequences of inflammatory
      and/or mechanical damage to the condylar cartilage.

PMID- 19164411
TI  - Immediate loading of orthodontic mini-implants: a histomorphometric evaluation of
      tissue reaction.
AB  - Although immediate loading of orthodontic mini-implants can be clinically
      successful, a lack of histological data exists. The present investigation was
      performed to evaluate, in an animal model, tissue reaction to immediate loading.
      Fifty orthodontic titanium mini-implants were inserted in four adult male monkeys
      at four time intervals. Forty-two devices were loaded with 50 cN super-elastic
      coil springs immediately after insertion while eight were left unloaded and
      served as the controls. After euthanasia, the following histomorphometric
      parameters were evaluated: bone volume (BV/TV), bone-to-implant contact (BIC),
      mineralizing surface (MS/BS), and erosion surface (ES/BS). Statistical analysis
      was performed by means of non-parametric tests. Four devices were removed because
      of loss of stability. A wide variation between animals was found for all
      parameters. BV/TV: slightly higher values were found in the unloaded sample.
      Although no particular trend was observed, at 3 months higher values were found
      in the lower jaw. BIC: a trend to a decrease between 1 week and 1 month followed
      by a significantly progressive increase was observed. Implants that showed some
      sections with as little as 3 per cent BIC successfully resisted loading. MS/BS:
      higher values were found in the lower jaw. MS/BS increased significantly between
      1 week and 1 month, followed by a progressive decrease. ES/BS: there was a
      decrease between 1 week and 1 month, followed by a progressive re-increase. BV/TV
      did not show any particular trend while BIC was a time-dependent factor. MS/BS
      and ES/BS demonstrated opposite trends during the healing period. Immediate
      loading with light forces did not negatively affect the bone healing pattern.

PMID- 19164412
TI  - Variation in dentofacial morphology and occlusion in juvenile idiopathic
      arthritis subjects: a case-control study.
AB  - Juvenile idiopathic arthritis (JIA) can severely disturb facial growth and affect
      occlusal development. In this case-control study, facial, functional, and
      occlusal characteristics of 100 JIA patients (35 males and 65 females; age range:
      1.7-19.4 years) comprising all subtypes classified according to the revised
      classification criteria of the International League of Associations for
      Rheumatology (ILAR) were studied. They were compared with a mixed orthodontic
      control group (n=32; 12 males and 20 females) and with a Class II division 1
      malocclusion group (n=19; eight males and 11 females). The JIA patients and
      controls were evaluated using clinical assessment, dental pantomograms, lateral
      cephalograms (LCGs), and dental casts. Compared with the age- and gender-matched
      mixed orthodontic controls, JIA patients showed a significantly greater
      prevalence of anterior open bites (AOBs; P<0.05; Wilcoxon matched pairs test).
      Cephalometrically, a larger mandibular plane (P<0.05) and SNA (P<0.001) angles
      and a smaller interincisal angle (P<0.001) were found. In comparison with the
      Class II division 1 controls, JIA patients showed a larger SNA (P<0.001; Wilcoxon
      matched pairs test) and SNB (P<0.05) angles and smaller lower anterior face
      heights (LAFHs; P<0.05). No differences were found for the mandibular plane, the
      gonial and the interincisal angles, or total face height. From this case-control
      study, it can be concluded that although JIA patients share occlusal
      characteristics with non-JIA patients with a Class II division 1 malocclusion,
      they are different with regard to the prevalence of condylar lesions and AOBs, as
      well as SNA and SNB angles and LAFH.

PMID- 19164413
TI  - Debonding characteristics of a polymer mesh base ceramic bracket bonded with two
      different conditioning methods.
AB  - The aim of this study was to compare the shear bond strength (SBS) and debonding
      characteristics of a polymer mesh base ceramic bracket bonded with two different
      surface conditioning methods. InVu Readi-Base ceramic brackets were bonded to 100
      human premolars with different etching protocols. With conventional method (CM),
      the teeth were etched with 37 per cent phosphoric acid for 30 seconds, while
      Transbond Plus self-etching primer (SEP) was applied as recommended by the
      manufacturer. SBS testing was performed on 25 samples of each group while the
      remaining 25 samples of each group were subjected to plier or machine debonding
      after thermocycling for 1000 cycles. The adhesive remnant index (ARI) was used to
      determine the amount of composite resin on the enamel. Statistical analysis
      included Kruskal-Wallis and Mann-Whitney U-tests and Weibull analysis. No
      significant difference was observed between the CM (9.22 MPa) and SEP (9.04 MPa)
      groups (P=0.684). ARI scores of machine and plier debonding for both groups
      showed a significant difference (P <or= 0.0001). Debonding with pliers showed a
      pronounced number of ARI scores of 3 for both groups. Polymer mesh base fractures
      were observed for both groups. Nevertheless, no significant differences were
      observed between the groups (chi(2)=4.304, P=0.230). The results of this in vitro
      study are encouraging, since, for the majority of specimens, all of the residual
      adhesive remained on the enamel surface. This type of debonding pattern has the
      advantage of protecting the enamel surface. Nevertheless, the base fractures at
      the ceramic/polymer interface might necessitate modifications in debonding
      strategy.

PMID- 19164414
TI  - Technique of laparoscopic ventral hernia repair can be modified to successfully
      repair large defects in patients with loss of domain.
AB  - BACKGROUND: Laparoscopic ventral hernia repair (LVHR) can be challenging in
      patients with large abdominal wall defects and loss of domain (LOD). When hernia
      contents are reduced, the pneumoperitoneum preferentially fills the sac, leaving
      no space for mesh manipulation. This study presents a modification for LVHR in
      LOD patients, as well as outcomes for a series of patients. METHODS: Between
      September 2002 and August 2004, 10 patients with large ventral hernias and LOD
      underwent attempts at LVHR. The technique is modified by placing additional
      trocars to allow for fixation from above the mesh. Patient data were harvested
      from a prospective database and analyzed. RESULTS: All hernias were recurrent in
      nature. Mean defect size was 626 cm(2), requiring 1 to 4 pieces of sutured Gore
      Dualmesh for a tension-free repair. Three patients' procedures were aborted after
      adhesiolysis, with concerns about missed enterotomies. All 3 underwent delayed
      mesh placement within the same hospitalization. Only 2 were successful. The third
      patient had significant bowel edema precluding mesh placement. Two patients were
      converted to open repairs (Rives-Stoppa and component separation). There were no
      mortalities, but there were 2 major complications: inferior vena cava thrombosis
      and transient abdominal compartment syndrome. In follow-up (7.7 months) there
      were 2 recurrences secondary to excision of infected mesh. CONCLUSION: It is
      possible to obtain a successful LVHR in patients with large defects and LOD. The
      technique is complex and is modified to allow for mesh fixation from above the
      mesh. Frequent change in patient positioning allows for visualization below the
      fascial defect.

PMID- 19164415
TI  - A case report of a double advancement flap closure combined with an Ilizarov
      technique for the chronic plantar forefoot ulceration.
AB  - Soft tissue closure of defects on the plantar surface of the foot continues to be
      a challenge for the reconstructive surgeon secondarily to the limited number of
      surgical options and often difficulty of replacing durable and similar soft
      tissue coverage. Primary closure and skin grafting may not be suitable for the
      weight-bearing surfaces of the plantar forefoot area, and closure may then be
      obtained by other means of plastic surgery techniques.

PMID- 19164416
TI  - Finding the culprit: a review of the influences of proteases on the chronic wound
      environment.
AB  - Chronic leg ulcers are a complex medical condition with varied underlying causes
      and requiring diverse treatment strategies. It is generally accepted that chronic
      ulcers occur when the normal wound healing process is interrupted. These wounds
      are characterized by excessive protease activity, abundant granulation tissue,
      and decreased levels of growth factors, resulting in an overall poor prognosis
      for the patient. Many studies have focused on identifying the key proteases,
      specifically matrix metalloproteinases (MMPs), responsible for an ulcer's
      chronicity. Of note, the results of these studies are often conflicting. This
      report therefore focuses on a review of this literature to identify which MMPs
      are important in terms of ulcer prognosis and healing outcome. This has revealed
      that MMPs are clearly important in many biological processes in wound healing,
      hence are critical to consider when developing improved therapies to enhance both
      ulcer healing times and ulcer healing outcomes.

PMID- 19164417
TI  - A paediatric case of acute liver failure associated with efavirenz-based highly
      active antiretroviral therapy and effective use of raltegravir in combination
      antiretroviral treatment after liver transplantation.

PMID- 19164418
TI  - Activity of oxazolidinone TR-700 against linezolid-susceptible and -resistant
      staphylococci and enterococci.
AB  - BACKGROUND: TR-700 is the active moiety of TR-701 (DA-7157), a new
      oral/intravenous oxazolidinone prodrug. We examined its activity against
      linezolid-susceptible and -resistant staphylococci and enterococci. METHODS: MICs
      were determined by the CLSI agar dilution method. RESULTS: MICs of TR-700 were
      tightly clustered around 0.5 mg/L for linezolid-susceptible staphylococci and
      enterococci compared with 2 mg/L for linezolid. MICs for 52 linezolid-resistant
      isolates were raised, but only exceeded 4 mg/L for two Enterococcus faecium
      isolates homozygous for the G2576T 23S rRNA mutation and for one with an unknown
      mechanism of linezolid resistance. CONCLUSIONS: TR-700 is 4- to 16-fold more
      active than linezolid and overcame most linezolid resistance in vitro.

PMID- 19164421
TI  - Environmental exposures and invasive meningococcal disease: an evaluation of
      effects on varying time scales.
AB  - Invasive meningococcal disease (IMD) is an important cause of meningitis and
      bacteremia worldwide. Seasonal variation in IMD incidence has long been
      recognized, but mechanisms responsible for this phenomenon remain poorly
      understood. The authors sought to evaluate the effect of environmental factors on
      IMD risk in Philadelphia, Pennsylvania, a major urban center. Associations
      between monthly weather patterns and IMD incidence were evaluated using
      multivariable Poisson regression models controlling for seasonal oscillation.
      Short-term weather effects were identified using a case-crossover approach. Both
      study designs control for seasonal factors that might otherwise confound the
      relation between environment and IMD. Incidence displayed significant wintertime
      seasonality (for oscillation, P < 0.001), and Poisson regression identified
      elevated monthly risk with increasing relative humidity (per 1% increase,
      incidence rate ratio = 1.04, 95% confidence interval: 1.004, 1.08). Case
      crossover methods identified an inverse relation between ultraviolet B radiation
      index 1-4 days prior to onset and disease risk (odds ratio = 0.54, 95% confidence
      interval: 0.34, 0.85). Extended periods of high humidity and acute changes in
      ambient ultraviolet B radiation predict IMD occurrence in Philadelphia. The
      latter effect may be due to decreased pathogen survival or virulence and may
      explain the wintertime seasonality of IMD in temperate regions of North America.

PMID- 19164422
TI  - Years-needed-to-treat to add 1 year of life: a new metric to estimate treatment
      effects in randomized trials.
AB  - AIMS: A standard metric to estimate absolute treatment effects is numbers-needed
      to-treat (NNT), which implicitly assumes that all benefits reverse at trial-end.
      However, in-trial survival benefits typically do not reverse until long after
      trial-end, so that NNT will substantially underestimate lifetime benefits.
      METHODS AND RESULTS: We developed a new concept, years-needed-to-treat (YNT) to
      add 1 year of life, that quantifies the expected average life expectancy for two
      treatments including the estimated years of life remaining post-trial. Numbers
      needed-to-treat and YNT were calculated in the COMET trial, in which carvedilol
      vs. metoprolol tartrate resulted in 17% lower mortality over 4.8 years. A
      multivariate Cox model was used to predict survival. Remaining years of life were
      estimated using the mortality-life-table method. At trial-end, survival was 9%
      higher in the carvedilol arm. Assuming that patients remained on the same therapy
      post-trial, the average total years of life for carvedilol vs. metoprolol were
      10.63 +/- 0.19 vs. 9.48 +/- 0.18 (P < 0.0001) or 1.15 (95% confidence interval
      0.64-1.66) additional years of life. The YNT was 9.2, indicating that 9.2 person
      years of treatment added 1 person-year of life, compared with NNT of 59.
      CONCLUSION: Compared with NNT, the YNT method more accurately accounts for
      potential long-term benefits of interventions in randomized trials.

PMID- 19164423
TI  - Successful treatment with B-cell depleting therapy for refractory systemic onset
      juvenile idiopathic arthritis: a case report.

PMID- 19164424
TI  - Comment on: Systemic lupus erythematosus patients exhibit functional deficiencies
      of endothelial progenitor cells.

PMID- 19164425
TI  - Patients with ankylosing spondylitis have increased sick leave--a registry-based
      case-control study over 7 yrs.
AB  - OBJECTIVES: Using prospectively collected registry data to investigate sick leave
      (sickness benefit and sickness compensation) over a 7-yr period in patients with
      AS in comparison with population-based controls matched for age, sex and
      residential area. METHODS: We investigated 122 (21 women and 101 men) outpatients
      with AS in South Sweden, born 1942 or later, from rheumatology specialist care
      for their sick leave during a 7-yr period. Mean (S.D.) age was 43 (11) yrs and
      mean (S.D.) disease duration was 20 (11) yrs. Two controls per case, matched for
      age, sex and residential area were selected from the Swedish National Population
      Register. Data concerning sick leave for cases and controls, based on the
      subjects' unique 10-digit personal identification number, were retrieved from the
      national register of the Swedish Social Insurance Agency. RESULTS: More AS
      patients than controls were registered for sickness benefit (52 vs 36%, P < 0.01)
      and sickness compensation (42 vs 11%, P < 0.001). Cases had an increased risk for
      sick leave compared with controls with a relative risk of 1.8; 95% CI 1.5, 2.1;
      and cases had more days with sick leave than controls (median number of more days
      per year 30; 95% CI 2, 72). CONCLUSIONS: Using the Swedish Social Insurance
      Agency's registers for sick leave, we found that patients with AS in rheumatology
      specialist care in South Sweden have an increased level of sick leave compared
      with controls. These population-based registers have a great potential for
      studies of the effects of different interventions on sick leave.

PMID- 19164427
TI  - Association between social position and congenital anomalies: a population-based
      study among 19,874 Danish women.
AB  - AIMS: To examine the association between maternal and paternal educational level
      and household income and the risk of giving birth to a baby with a congenital
      anomaly in a population of Danish women. METHODS: We performed a population-based
      cohort study, based on record linkage of data from Danish administrative
      registries. For each pregnant woman in the cohort, we described financial and
      educational resources and congenital anomalies in her offspring. We used logistic
      regression to model the association between social position and congenital
      anomalies. RESULTS: The analyses included all 19,874 primiparous singleton
      deliveries in North Jutland county, Denmark, from 1991 to 1998. There were 1025
      (5.2%) babies with congenital anomalies. The odds ratios (ORs) for giving birth
      to a baby with a congenital anomaly showed a dose- response decline, as the
      mothers' educational level increased. Women with less than 10 years of schooling
      had an almost three-fold increased risk of giving birth to an infant with a
      congenital anomaly, as compared with women with more than 4 years of higher
      education (OR=2.9, 95% confidence interval = 1.8-4.6). Paternal educational level
      and household income were, to a lesser degree, associated with congenital
      anomalies in the offspring. CONCLUSIONS: Maternal educational level, and to a
      lesser degree paternal educational level and household income, were associated
      with the risk of giving birth to a baby with a congenital anomaly. However, the
      analysis did not take into account maternal health status, and the results might
      be due to differential misclassification or residual confounding.

PMID- 19164426
TI  - Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune
      uveitis.
AB  - OBJECTIVES: Human endogenous uveitis is one of the sight-threatening diseases
      associated with variety of systemic disorders, such as Behcet's disease and
      sarcoidosis. Recently, biosynthesized antibodies against inflammatory cytokines
      have been recognized to be useful to control the regional inflammation. In this
      study, we focused on the possibility of IL-6-based biological therapies for
      endogenous uveitis. We initially confirmed the significant increase of several
      inflammatory soluble factors including IL-6 in the vitreous fluids from
      refractory/chronic engogenous uveitis patients. METHODS: To investigate the role
      of IL-6 in the formation of refractory ocular inflammation, we used the mouse
      experimental autoimmune uveitis (EAU) model. Both IL-6 and IL-23 are required for
      the development of IL-17-producing helper T subset (Th17) from naive CD4(+) T
      cells. Results. In the EAU model, neither IL-6-deficient mice nor IL-23-deficient
      mice could induce Th17 cells and the EAU score was decreased in these mice in the
      entire time course. We also confirmed that systemic administration of anti-il-6
      receptor antibody ameliorates EAU By suppressing both systemic and regional TH17
      responses. CONCLUSIONS: IL-6 is responsible for causing ocular inflammation, and
      it is, at least partially, due to IL-6-dependent Th17 differentiation. IL-6 may
      be a target for therapy of refractory endogenous uveitis in humans.

PMID- 19164428
TI  - Poverty and non-communicable diseases in South Africa.
AB  - BACKGROUND: High levels of wealth inequality with improved health statistics in
      South Africa (SA) provide an important opportunity to investigate non
      communicable diseases (NCDs) among the poor. AIMS: This paper uses two distinct
      national data sets to contrast patterns of mortality in rich and poor areas and
      explore the associations between poverty, risk factors, health care and selected
      NCDs diseases in South African adults. METHODS: Causes of premature mortality in
      1996 experienced in the poorest magisterial districts are compared with those in
      the richest, using average household wealth to classify districts. Logistic and
      multinomial regression are used to investigate the association of a household
      asset index and selected chronic conditions, related risk factors and healthcare
      indicators using data from the 1998 South African Demographic and Health Survey.
      RESULTS: NCDs accounted for 39% and 33% of premature mortality in rich and poor
      districts respectively. The household survey data showed that the risk factors
      hypertension and obesity increased with increasing wealth, while most of the
      lifestyle factors, such as light smoking, domestic exposure to ;;smoky'' fuels
      and alcohol dependence were associated with poverty. Treatment status for
      hypertension and asthma was worse for poor people than for rich people.
      CONCLUSIONS: The study suggests that NCDs and lifestyle-related risk factors are
      prevalent among the poor in SA and treatment for chronic diseases is lacking for
      poor people. The observed increase in hypertension and obesity with wealth
      suggests that unless comprehensive health promotion strategies are implemented,
      there will be an unmanageable chronic disease epidemic with future socioeconomic
      development in SA.

PMID- 19164429
TI  - "It's about focusing on the mother's mental health'': screening for postnatal
      depression seen from the health visitors' perspective--a qualitative study.
AB  - AIMS: This study examines experiences from the implementation of EPDS as a
      routine screening for postnatal depression in a health centre seen from health
      visitors' perspective. METHODS: A qualitative approach was chosen to shed light
      on this issue. Six experienced health visitors and one midwife participated in a
      focus group interview sharing their experiences and expectations. RESULTS: The
      analysis indicate that the EPDS screening turned out to be a useful tool for the
      health visitors to adress mental health issues in health promotion and preventive
      work with mothers and newborns. The EPDS screening shifted the focus in the
      consultation from the child solely to also encompass the mother and the relation
      between them. A precondition for this was that the implementation process was
      gradual and on the health visitors own terms, likewise that there was a follow-up
      chain including supervision given to the health visitors, in order to provide
      help for the mothers who need more help than the health centre can offer.
      CONCLUSIONS: Our study shows that acceptability for routine screening with EPDS
      amongst health visitors is possible to achieve.

PMID- 19164430
TI  - Trends of tobacco use in Sweden and Finland: do differences in tobacco policy
      relate to tobacco use?
AB  - BACKGROUND: Sweden and Finland, neighbouring countries in Scandinavia, share
      features in health and social policies but retain a few differences in tobacco
      policy, including oral tobacco product regulation. This paper analyses the
      differences between tobacco policy and tobacco use between these two countries.
      MATERIAL: Representative data sets from both countries, for age groups 18 to 64,
      were used to compare the status of tobacco use. The study covered the years
      1988/89, 1996/97 and 2004/05. RESULTS: Among men, daily use of tobacco products
      is more common in Sweden than in Finland. The daily smoking rate for men in
      Sweden is 16% compared to 28% in Finland. In Sweden, 27% of men use snuff daily
      and 17% of never smoking men reported daily use of snuff. In Finland, 3% of all
      males report daily use of snuff. Concurrent snuff use was linked to occasional
      smoking in Sweden, where 23% of male daily snuff users smoke occasionally. Among
      women smoking prevalence has decreased significantly in Sweden during the study
      period, but no real change in daily smoking can be detected in Finland.
      CONCLUSIONS: Tobacco control measures did gain good results among women in Sweden
      whereas in Finland development was modest. In Sweden, tobacco use has increased
      mainly due to an increase in snuff use, and snuff seems to appeal not only to
      switchers, but to young males without a history of smoking.

PMID- 19164431
TI  - Individual and familial factors associated with teenage pregnancy: an interview
      study.
AB  - BACKGROUND: The determinants of teenage sexual health, including pregnancies, can
      be addressed from social, familial and individual level perspectives. The main
      objective of this study was to examine whether pregnancy among 18 years old and
      younger girls were associated with selected individual (age at coitarche, score
      of sexual health knowledge, dislike of school) and family (mother's education)
      and family functioning (alcohol abuse in the family, parents' acceptance of
      sexual relationship) characteristics. METHODS: An interview survey in two medical
      institutions in Estonia among 279 18 year old and younger girls, who: (i) used
      contraception, had been sexually active for at least 6 months and had not
      pregnancies--(148 girls); (ii) came for termination of pregnancy--abortion group;
      (iii) planned to deliver and came for prenatal care--delivery group. The last two
      groups were analysed together as the 'pregnancy group'--131 girls. Multivariate
      analysis, by means of logistic regression models, was used to explore whether the
      associations were sustained after adjusting for other variables. Crude odds
      ratios (ORs), adjusted ORs and their 95% confidence intervals (CIs) were
      estimated, with girls having no pregnancies as the reference group. RESULTS: Risk
      factors associated with teenage pregnancy were low score of sexual health
      knowledge (adjusted ORs 3.07; 95% CIs 1.73-5.46), dislike of school (adjusted ORs
      1.96; 95% CIs 1.08-3.54), alcohol abuse by family members (adjusted ORs 2.03; 95%
      CIs 1.16-3.54). CONCLUSION: Sexual knowledge of teenagers, their attitude towards
      school, alcohol abuse in the family are factors associated with teenage
      pregnancies.

PMID- 19164432
TI  - Contribution of a shelter-based survey for screening respiratory diseases in the
      homeless.
AB  - BACKGROUND: The homeless are at very high risk for both respiratory diseases and
      poor access to health care delivery systems. The aim of this study was to assess
      the contribution of a shelter-based survey to identify respiratory diseases in
      the homeless population in Marseilles, in order to further develop preventive
      interventions. METHODS: A prevalence survey of respiratory diseases was conducted
      in two homeless shelters in Marseilles, in February 2005. A multidisciplinary
      team including infectious diseases specialists, lung specialists, residents,
      nurses, physiotherapists and X-ray technicians visited the two shelters.
      Interview, physical examination, sputum sampling for Mycobacterium tuberculosis
      detection, nasal swabs for virus detection and chest X-rays were performed in
      shelters. Chest X-rays were subsequently analysed by a pneumonologist and
      subjects found to have radiological abnormalities were hospitalized for further
      investigations. RESULTS: Of the 221 homeless persons enrolled, 110/221 (50%) had
      at least one respiratory manifestations. Chest X-rays were abnormal in 14
      persons. Active tuberculosis was diagnosed in two, influenza in two, respiratory
      syncytial virus infection in two, acute pneumonia in one, asthma in two, lung
      cancer in one, acute bronchitis in 23, chronic bronchitis in 42, and exacerbation
      of chronic obstructive pulmonary disease in 22 persons, respectively. CONCLUSION:
      Our shelter-based survey, including clinical evaluation and chest radiographic
      screening, shows that this approach can be useful to control and prevent
      respiratory diseases among the homeless. However, further studies are necessary
      to determine the magnitude of influenza in the homeless, the impact of influenza
      immunization and optimal frequency of interventions in shelters.

PMID- 19164433
TI  - Optimising lifestyle interventions: identification of health behaviour patterns
      by cluster analysis in a German 50+ survey.
AB  - BACKGROUND: Many prevention and intervention measures are still targeting
      isolated behaviours such as tobacco use or physical inactivity. Cluster analysis
      enables the aggregation of single health behaviours in order to identify
      distinctive behaviour patterns. The purpose of this study was to group a sample
      of the over-50 population into clusters that exhibit specific health behaviour
      patterns regarding regular tobacco use, excessive alcohol consumption, unhealthy
      diet and physical inactivity. METHODS: From the total population of the federal
      state of Baden-Wuerttemberg, Germany, 982 men and 1020 women aged 50-70 were
      randomly selected. Subjects were asked by trained interviewers in computer
      assisted telephone interviews (CATI) about health behaviour and sociodemographic
      characteristics. Cluster analysis was conducted to identify distinct health
      behaviour patterns. Multinomial logistic regression was used to characterize
      clusters by specific social attributes. RESULTS: Five homogeneous health
      behaviour clusters were identified: 'No Risk Behaviours' (25.3%), 'Physically
      Inactives' (21.1%), 'Fruit and Vegetable Avoiders' (18.2%), 'Smokers with Risk
      Behaviours' (12.7%) and 'Drinkers with Risk Behaviours' (22.7%). Whereas the
      first cluster is the ideal in terms of risk and prevention, the latter two groups
      include regular users of tobacco and excessive consumers of alcohol, who also
      engage in other risk behaviours like inactivity and maintaining an unhealthy
      diet. These two risk groups also exhibit specific sociodemographic attributes
      (male, living alone, social class affiliation). CONCLUSION: Unhealthy behaviours
      evidently occur in typical combinations. An awareness of this clustering enables
      prevention and intervention measures to be planned so that multiple behaviours
      can be modified simultaneously.

PMID- 19164434
TI  - Long-term control of disseminated pleomorphic xanthoastrocytoma with anaplastic
      features by means of stereotactic irradiation.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm of the brain.
      Some PXAs are accompanied by anaplastic features and are difficult to manage
      because of frequent recurrences that lead to early death. No previous reports
      have demonstrated consistent efficacy of adjuvant radiotherapy or chemotherapy
      for this disease. We report a case of PXA with anaplastic features treated with
      stereotactic irradiation (STI) that resulted in long-term control of repeatedly
      recurring nodules throughout the neuraxis. A 47-year-old woman presented with an
      epileptic seizure due to a large tumor in the right frontal lobe. The tumor was
      resected and diagnosed as PXA with anaplastic features. Sixteen months later, a
      relapse at the primary site was noted and treated with stereotactic radiosurgery
      using Gamma Knife. Two years later, the patient developed a tumor nodule in the
      cervical spinal cord that histologically corresponded to a small-cell glioma with
      high cellularity and prominent MIB-1 (mindbomb homolog 1) labeling. In the
      following months, multiple nodular lesions appeared throughout the CNS, and STI
      was performed six times for eight intracranial lesions using Gamma Knife and
      twice using a linear accelerator, for three spinal cord lesions in total. All
      lesions treated with STI were well controlled, and the patient was free from
      symptomatic progression for 50 months. However, diffuse dissemination along the
      craniospinal axis eventually progressed, and she died 66 months after initial
      diagnosis. Autopsy showed that the nodules remained well demarcated from the
      surrounding nervous system tissue. STI may be an effective therapeutic tool for
      controlling nodular dissemination of PXA with anaplastic features.

PMID- 19164435
TI  - Plasma IGFBP-2 levels predict clinical outcomes of patients with high-grade
      gliomas.
AB  - Insulin-like growth factor binding protein 2 (IGFBP-2) is a malignancy-associated
      protein measurable in tumors and blood. Increased IGFBP-2 is associated with
      shortened survival of advanced glioma patients. Thus, we examined plasma IGFBP-2
      levels in glioma patients and healthy controls to evaluate its value as a plasma
      biomarker for glioma. Plasma IGFBP-2 levels in 196 patients with newly diagnosed
      glioma and 55 healthy controls were analyzed using an IGFBP-2 ELISA kit. Blood
      was collected before surgery, after two-cycle adjuvant chemotherapy, and at
      recurrence. Plasma IGFBP-2 levels were correlated with disease-free survival
      (DFS) using Cox regression analyses. We found that preoperative plasma IGFBP-2
      levels were significantly higher in high-grade glioma patients (n = 43 for grade
      III glioma; n = 72 for glioblastoma multiforme [GBM]) than in healthy controls (n
      = 55; p < 0.001) and low-grade (grade II) glioma patients (n = 81; p < 0.001). No
      significant differences in preoperative plasma IGFBP-2 levels were observed
      between grade III glioma and GBM patients or between grade II glioma patients and
      healthy controls. After recurrence, plasma IGFBP-2 levels were significantly
      increased in GBM patients (n = 26; p < 0.001). Preoperative plasma IGFBP-2 levels
      were significantly correlated with DFS in GBM patients (hazard ratio, 1.404; 95%
      confidence interval, 1.078-1.828; p = 0.012). We conclude that preoperative
      plasma IGFBP-2 levels are significantly higher in high-grade glioma patients than
      in low-grade glioma patients and healthy subjects, and are significantly
      correlated with recurrence and DFS in patients with GBM. Longitudinal studies
      with a larger study population are needed to confirm these findings.

PMID- 19164436
TI  - Comparing and predicting the costs and outcomes of patients with major and minor
      stroke using the Boston Acute Stroke Imaging Scale neuroimaging classification
      system.
AB  - BACKGROUND AND PURPOSE: A neuroimaging-based ischemic stroke classification
      system that predicts costs and outcomes would be useful for clinical
      prognostication and hospital resource planning. The Boston Acute Stroke Imaging
      Scale (BASIS), a neuroimaging-based ischemic stroke classification system, was
      tested to determine whether it was able to predict the costs and clinical
      outcomes of patients with stroke at an urban academic medical center. MATERIALS
      AND METHODS: Patients with ischemic stroke who presented in the emergency
      department in 2000 (230 patients) and 2005 (250 patients) were classified by
      using BASIS as having either a major or minor stroke. Compared outcomes included
      death, length of hospitalization, discharge disposition, use of imaging and
      intensive care unit (ICU) resources, and total in-hospital cost. Continuous
      variables were compared by univariate analysis by using the Student t test or the
      Satterthwaite test adjusted for unequal variances. Categoric variables were
      tested with the chi(2) test. Multiple regression analyses related total hospital
      cost (dependent variable) to stroke severity (major versus minor), sex, age,
      presence of comorbidities, and death during hospitalization. Logistic regression
      analysis was applied to identify the significant predictive variables indicating
      a greater likelihood of discharge home. RESULTS: In both years, individuals with
      strokes classified as major had a significantly longer length of stay, spent more
      days in the ICU, and had a higher cost of hospitalization than patients with
      minor strokes (all outcomes, P < .0001). All deaths (8 in 2000, 26 in 2005)
      occurred in patients with major stroke. Whereas 73% of patients with minor stroke
      were discharged home, only 12.2% of patients with major stroke were discharged
      home (P < .0001); 61% of patients with major stroke were discharged to a
      rehabilitation or skilled nursing facility. Patients with major stroke cost 4.4
      times and 3.0 times that of patients with minor stroke in 2000 and 2005,
      respectively. Making up less than one third of all patients, patients with major
      stroke accounted for 60% of the total in-hospital cost of acute stroke care.
      CONCLUSIONS: BASIS, a neuroimaging-based stroke classification system, is highly
      effective at predicting in-hospital resource use, acute-hospitalization cost, and
      outcome. Predictive ability was maintained across the years studied.

PMID- 19164437
TI  - Perfusion CT in patients with acute ischemic stroke treated with intra-arterial
      thrombolysis: predictive value of infarct core size on clinical outcome.
AB  - BACKGROUND AND PURPOSE: A potential role of perfusion CT (PCT) in selecting
      patients with stroke for reperfusion therapies has been recently advocated. The
      purpose of the study was to assess the reliability of PCT in predicting clinical
      outcome of patients with acute ischemic stroke treated with intra-arterial
      thrombolysis (IAT). MATERIALS AND METHODS: Twenty-seven patients with acute
      hemispheric ischemic stroke were investigated with PCT and treated with IAT
      between 3 and 6 hours of stroke onset. The infarct core was outlined on cerebral
      blood volume (CBV) maps by using accepted viability thresholds. The penumbra was
      defined as time-to-peak (TTP)-CBV mismatch. Clinical outcome was assessed by
      modified Rankin Scale (mRS) scores at 3 months and dichotomized into favorable
      (mRS score, 0-2) and unfavorable (mRS score, 3-6). Data were retrospectively
      analyzed by multiple regression to identify predictors of clinical outcome among
      the following variables: age, sex, National Institutes of Health Stroke Scale
      score, serum glucose level, thrombolytic agent, infarct core and mismatch size,
      collateral circulation, time to recanalization, and recanalization rate after
      IAT. RESULTS: Patients with favorable outcome had smaller cores (P = .03),
      increased mismatch ratios (P = .03), smaller final infarct sizes (P < .01),
      higher recanalization rates (P = .03), and reduced infarct growth rates (P <
      .01), compared with patients with unfavorable outcome. The core size was the
      strongest predictor of clinical outcome in an "all subset" model search (P = .01;
      0.96 point increase in mRS score per any increment of 1 SD; 95% confidence
      interval, +0.17 to +1.75). CONCLUSIONS: PCT is a reliable tool for the
      identification of irreversibly damaged brain tissue and for the prediction of
      clinical outcome of patients with acute stroke treated with IAT.

PMID- 19164438
TI  - Vertebral artery dissection with a normal-appearing lumen at multisection CT
      angiography: the importance of identifying wall hematoma.
AB  - BACKGROUND AND PURPOSE: CT angiography (CTA) is widely used and may be the only
      vascular imaging technique ordered for emergent evaluation of neurovascular
      disease. With thin-section multisection CTA, the resolution of vessel wall
      imaging has improved. We describe cases of acute vertebral artery dissection
      (VAD) in which the only abnormality on CTA was a characteristic thickening of the
      wall of the V3 portion of the vertebral artery (VA). The arterial lumen at the
      dissection site was normal in caliber. This type of dissection is easily
      overlooked if only lumen-opacifying studies such as contrast MR angiography (MRA)
      or conventional angiography are performed. We highlight the importance of
      recognizing this finding, the "suboccipital rind" sign, in the V3 portion, a
      segment commonly affected in VAD. The purpose of our study was to review the CTA
      imaging characteristics of patients with VAD in the V3 portion compared with
      normal controls. MATERIALS AND METHODS: Our imaging data base was reviewed for
      cases of acute VAD and the presence of a "suboccipital rind" sign. A control
      group of 50 patients was randomly recruited from a group of patients undergoing
      CTA. The VA luminal diameter, the wall thickness (total diameter-luminal
      diameter), and the ratio of luminal diameter/total diameter were measured along 5
      adjacent V3 segments and were compared between the 2 groups. RESULTS: There was
      no evidence of luminal tapering or narrowing in the dissected VAs compared with
      controls (P = .1). The average wall thickness of the dissection group was 2.96 mm
      greater than that for the control group (P < .001; 95% confidence interval, 2.6
      3.3). There was a significant difference in the ratio of lumen
      diameter/lumen+wall diameter in dissected segments compared with controls (P <
      .001). CONCLUSIONS: Cross-sectional vascular imaging is often performed with
      multisection helical CTA for a variety of concerns, some without neurologic
      symptoms. Our study confirms that in cases of the "suboccipital rind" sign, the
      lumen appears normal in caliber, with wall thickening as the only imaging sign of
      VAD. In our center, this clinically occult VAD would influence management, with
      patients usually treated with antiplatelet agents. We caution against using only
      luminal-opacifying techniques such as contrast-enhanced MRA or conventional
      angiography to exclude VAD because they are limited in the evaluation of mural
      hematoma.

PMID- 19164439
TI  - MR imaging findings of the uveal schwannoma.
AB  - BACKGROUND AND PURPOSE: Uveal schwannoma is a rare benign neoplastic
      proliferation of pure Schwann cells. The purpose of this study was to describe MR
      imaging features of uveal schwannoma. MATERIALS AND METHODS: MR images in 6
      female patients with uveal schwannoma confirmed by pathologic examination were
      retrospectively reviewed. MR imaging was performed in all 6 patients, with
      postcontrast T1-weighted imaging (T1WI) completed in all 6 patients and dynamic
      contrast-enhanced MR imaging, in 5. MR imaging findings of the tumor were
      evaluated with emphasis on the location, size, shape, margin, signal intensity,
      and pattern of enhancement. RESULTS: The lesions appeared as solitary well
      defined ovoid masses in the ciliochoroidal region in 5 patients and in the
      choroid in 1. With respect to the vitreous body, uveal schwannoma was
      hyperintense on T1WI spin-echo (SE) images in all 6 patients. The tumors were
      hypointense to the vitreous body on fast SE (FSE) T2-weighted images (T2WI) in 4
      patients and isointense in 1. However, with respect to the brain, uveal
      schwannoma demonstrated isointensity on T1WI SE images in all 6 patients,
      isointensity on FSE T2WI images in 5 patients, and hyperintensity on T2WI SE
      images in 1. On postcontrast T1WI images, 3 patients showed markedly
      heterogeneous enhancement, and 3 showed markedly homogeneous enhancement.
      CONCLUSIONS: Uveal schwannoma should be included in the differential diagnosis
      when an oval isointense mass relative to brain is seen in the ciliochoroidal
      region.

PMID- 19164440
TI  - Contrast-enhanced MR angiography is not more accurate than unenhanced 2D time-of
      flight MR angiography for determining > or = 70% internal carotid artery
      stenosis.
AB  - BACKGROUND AND PURPOSE: Internal carotid artery (ICA) atheromatous disease is an
      important cause of ischemic stroke, and endarterectomy or stent placement is
      typically indicated for symptomatic patients with > or = 70% stenosis. Our
      purpose was to compare contrast-enhanced MR angiography (CE-MRA) with unenhanced
      2D time-of-flight MR angiography (2D TOF MRA) in detecting hemodynamically
      significant ICA stenosis, by using CT angiography (CTA) as the reference
      standard. MATERIALS AND METHODS: This was an institutional review board-approved
      retrospective study. We identified 177 consecutive patients (354 ICAs) who
      received correlative CE-MRA, 2D TOF MRA, and CTA. Two neuroradiologists blinded
      to the CTA data graded the degree of ICA stenosis according to a 5-point scale.
      Additionally, luminal signal-intensity characteristics including 1) signal
      intensity drop-out, 2) distal-vessel narrowing, and 3) distal-vessel signal
      intensity reduction were recorded. MRA results were correlated with those of CTA,
      and receiver-operating-characteristic (ROC) curves were constructed. RESULTS: On
      CTA, there were 55 ICAs with and 299 without > or = 70% stenosis. CE-MRA was 84%
      sensitive and 96% specific for detecting > or = 70% stenosis; 2D TOF MRA was 80%
      sensitive and 95% specific. The area under the ROC curve was 0.97 for CE-MRA and
      0.95 for 2D TOF MRA (P = .51, not significant). For both MRA studies, each of the
      luminal signal-intensity characteristics had high specificity (> 98%) but poor-to
      mild sensitivity (35%-66%) in detecting > or = 70% stenosis. CONCLUSIONS:
      Although it is established that CE-MRA more accurately delineates neurovascular
      anatomy than does unenhanced 2D TOF MRA, the administration of gadolinium did not
      offer a significant advantage in distinguishing surgically treatable ICA
      stenosis. This conclusion may be important in patients with contraindications to
      gadolinium.

PMID- 19164441
TI  - The frequency and extent of mammillary body atrophy associated with surgical
      removal of a colloid cyst.
AB  - BACKGROUND AND PURPOSE: Patients who have had a colloid cyst removed from the
      third ventricle sometimes experience some difficulty with day-to-day memory. This
      study provided quantitative MR imaging volume measures of 1 structure potentially
      responsible for mnemonic problems, the mammillary bodies. Additional volume
      estimates in structures connected to the mammillary bodies sought to determine
      the specificity of any atrophy. MATERIALS AND METHODS: Volume estimates of the
      mammillary bodies were performed on 38 patients after surgical removal of colloid
      cysts and 20 control subjects by the application of stereologic volume-estimation
      techniques. For the mammillary body measures, 2 groups of MR images were assessed
      (0.8- and 1.0-mm section thickness) to compare the sensitivity of each imaging
      sequence for detecting any atrophy. Other structures associated with memory
      processes, such as the hippocampus and fornix, were also assessed quantitatively
      to determine whether there was a correlation between mammillary body damage and
      atrophy in connecting structures. RESULTS: Our investigations established the
      superiority of 0.8-mm-volume scans over standard isotropic 1.0-mm-thick-volume
      scans for mammillary body assessments. Comparisons with 20 age-matched controls
      revealed that patients with colloid cysts frequently showed significant
      mammillary body atrophy (mean volume of colloid cysts, 0.037 cm(3) right and
      0.038 cm(3) left; control subjects, 0.069 cm(3) right and 0.067 cm(3) left). In
      fact, every patient had a mammillary body volume below the control mean, and the
      majority of patients had a volume decrease of >1 SD (82% right, 74% left).
      Mammillary body volumes correlated with fornix volumes in the same patient group.
      CONCLUSIONS: Our results reveal the frequent presence of mammillary body atrophy
      in patients with surgical removal of colloid cysts and indicate that this atrophy
      is partly due to a loss of temporal lobe projections in the fornix.

PMID- 19164442
TI  - CT and MR imaging features of primary central nervous system lymphoma in Norway,
      1989-2003.
AB  - BACKGROUND AND PURPOSE: Studying imaging findings of non-acquired
      immunodeficiency syndrome (AIDS) primary central nervous system lymphoma (PCNSL),
      we hypothesized that the imaging presentation has changed with the increasing
      incidence of PCNSL and is related to clinical factors (eg, time to diagnosis and
      the patient's being diagnosed alive or at postmortem examination). MATERIALS AND
      METHODS: Chart and histologic reviews of patients recorded as having PCNSL during
      1989-2003 in the Norwegian Cancer Registry identified 98 patients with non-AIDS
      PCNSL; 75 had available imaging. CT and MR images from the first diagnostic work
      up after onset of symptoms but before histologic diagnosis were reviewed.
      RESULTS: CT and/or MR imaging in the 75 patients revealed no lesion in 10 (13%),
      a single focal lesion in 34 (45%), multiple focal lesions in 26 (35%), and
      disseminated lesions in 5 (7%) patients. All together, we identified 103 focal
      lesions (single/multiple): 63% in white matter, 56% abutting the ventricular
      surface, and 43% in the frontal lobes); 100% (102/102 lesions evaluated with
      contrast) showed contrast enhancement. The median time from imaging to diagnosis
      for patients with no, single, multiple, or disseminated lesions was 32, 3, 5, and
      3 weeks, respectively (P = .01). Patients with no or disseminated lesions were
      more often diagnosed at postmortem examination (P = .06). Imaging findings were
      practically unchanged during the consecutive 5-year periods. CONCLUSIONS: White
      matter periventricular contrast-enhancing single or multiple focal lesions were
      typical of non-AIDS PCNSL. No or disseminated lesions heightened the risk of
      delayed or postmortem diagnosis. Although the incidence of non-AIDS PCNSL has
      increased, its presentation at imaging remains unchanged.

PMID- 19164443
TI  - Regulation of group II metabotropic glutamate receptors by G protein-coupled
      receptor kinases: mGlu2 receptors are resistant to homologous desensitization.
AB  - We examined the regulation of mGlu2 and mGlu3 metabotropic glutamate receptor
      signaling prompted by the emerging role of these receptor subtypes as therapeutic
      targets for psychiatric disorders, such as anxiety and schizophrenia. In
      transfected human embryonic kidney 293 cells, G-protein-coupled receptor kinase
      (GRK) 2 and GRK3 fully desensitized the agonist-dependent inhibition of cAMP
      formation mediated by mGlu3 receptors. In contrast, GRK2 or other GRKs did not
      desensitize the cAMP response to mGlu2 receptor activation. Desensitization of
      mGlu3 receptors by GRK2 required an intact kinase activity, as shown by the use
      of the kinase-dead mutant GRK2-K220R or the recombinant GRK2 C-terminal domain.
      Overexpression of beta-arrestin1 also desensitized mGlu3 receptors and did not
      affect the cAMP signaling mediated by mGlu2 receptors. The difference in the
      regulation of mGlu2 and mGlu3 receptors was signal-dependent because GRK2
      desensitized the activation of the mitogen-activated protein kinase pathway
      mediated by both mGlu2 and mGlu3 receptors. In vivo studies confirmed the
      resistance of mGlu2 receptor-mediated cAMP signaling to homologous
      desensitization. Wild-type, mGlu2(-/-), or mGlu3(-/-) mice were treated
      intraperitoneally with saline or the mixed mGlu2/3 receptor agonist (-)-2-oxa-4
      aminobicyclo[3.1.0]-exhane-4,6-dicarboxylic acid (LY379268; 1 mg/kg) once daily
      for 7 days. Inhibition of forskolin-stimulated cAMP formation by LY379268 was
      measured in cortical slices prepared 24 h after the last injection. Agonist
      pretreatment fully desensitized the cAMP response in wild-type and mGlu2(-/-)
      mice but had no effect in mGlu3(-/-) mice, in which LY379268 could only activate
      the mGlu2 receptor. We predict the lack of tolerance when mixed mGlu2/3 receptor
      agonists or selective mGlu2 enhancers are used continually in patients.

PMID- 19164444
TI  - Minireview: protein arginine methylation of nonhistone proteins in
      transcriptional regulation.
AB  - Endocrine regulation frequently culminates in altered transcription of specific
      genes. The signal transduction pathways, which transmit the endocrine signal from
      cell surface to the transcription machinery, often involve posttranslational
      modifications of proteins. Although phosphorylation has been by far the most
      widely studied protein modification, recent studies have indicated important
      roles for other types of modification, including protein arginine methylation.
      Ten different protein arginine methyltransferase (PRMT) family members have been
      identified in mammalian cells, and numerous substrates are being identified for
      these PRMTs. Whereas major attention has been focused on the methylation of
      histones and its role in chromatin remodeling and transcriptional regulation,
      there are many nonhistone substrates methylated by PRMTs. This review primarily
      focuses on recent progress on the roles of the nonhistone protein methylation in
      transcription. Protein methylation of coactivators, transcription factors, and
      signal transducers, among other proteins, plays important roles in
      transcriptional regulation. Protein methylation may affect protein-protein
      interaction, protein-DNA or protein-RNA interaction, protein stability,
      subcellular localization, or enzymatic activity. Thus, protein arginine
      methylation is critical for regulation of transcription and potentially for
      various physiological/pathological processes.

PMID- 19164445
TI  - Liver X receptor ligands suppress ubiquitination and degradation of LXRalpha by
      displacing BARD1/BRCA1.
AB  - Liver X receptor (LXR) is a ligand-activated transcription factor that plays
      important roles in cholesterol and lipid homeostasis. However, ligand-induced
      posttranslational modification of LXR is largely unknown. Here, we show that
      ligand-free LXRalpha is rapidly degraded by ubiquitination. Without ligand,
      LXRalpha interacts with an ubiquitin E3-ligase protein complex containing breast
      and ovarian cancer susceptibility 1 (BRCA1)-associated RING domain 1 (BARD1).
      Interestingly, LXR ligand represses ubiquitination and degradation of LXRalpha,
      and the interaction between LXRalpha and BARD1 is inhibited by LXR ligand.
      Consistently, T0901317, a synthetic LXR ligand, increased the level of LXRalpha
      protein in liver. Moreover, overexpression of BARD1/BRCA1 promoted the
      ubiquitination of LXRalpha and reduced the recruitment of LXRalpha to the target
      gene promoters, whereas BARD1 knockdown reversed such effects. Taken together,
      these data suggest that LXR ligand prevents LXRalpha from ubiquitination and
      degradation by detaching BARD1/BRCA1, which might be critical for the early step
      of transcriptional activation of ligand-stimulated LXRalpha through a stable
      binding of LXRalpha to the promoters of target genes.

PMID- 19164446
TI  - Interruption of growth hormone signaling via SHC and ERK in 3T3-F442A
      preadipocytes upon knockdown of insulin receptor substrate-1.
AB  - Insulin receptor substrate-1 (IRS-1) is a docking protein tyrosine phosphorylated
      in response to insulin, IGF-1, GH, and other cytokines. IRS-1 has an N-terminal
      plekstrin homology domain (which facilitates membrane localization), a
      phosphotyrosine-binding domain [which associates with tyrosine-phosphorylated
      insulin receptor or IGF-1 receptor (IGF-1R)], and tyrosine residues that, when
      phosphorylated, bind signaling molecules. The role of IRS-1 in GH signaling is
      uncertain. We previously reported that IRS-1 and Janus kinase 2 associate
      independently of tyrosine phosphorylation via IRS-1's N terminus and that IRS-1
      reconstitution greatly enhances GH-induced ERK, but not STAT5, activation. We now
      use GH-responsive 3T3-F442A preadipocytes to study the influence of IRS-1 on GH
      action. We stably transfected cells with vector only (Control) or a vector
      encoding IRS-1 short hairpin RNA [knockdown (KD)] and compared representative
      clones. Immunoblotting confirmed more than 80% knockdown of IRS-1 in KD cells. GH
      caused characteristic Janus kinase 2 and STAT5 activation in both Control and KD
      cells, but ERK activation was dramatically reduced in KD cells in GH time course
      and dose-response experiments. Notably, GH-induced Src homology collagen (SHC)
      activation and SHC-Grb2 association in KD cells were also markedly diminished
      compared with Control cells. Subcellular fractionation revealed that IRS-1 in
      Control cells was largely cytosolic, but the component isolated with plasma
      membranes was highly enriched in lipid raft membranes (LR). In KD cells, GH
      induced ERK activation in the LR fraction was particularly diminished compared
      with Control cells. These data suggest that LR-enriched IRS-1 contributes
      substantially to GH-induced ERK activation in LR in 3T3-F442A fibroblasts.
      Furthermore, our results are consistent with IRS-1 residing upstream of SHC in
      the GH-induced ERK-signaling pathway.

PMID- 19164447
TI  - Androgen modulation of coregulator expression in prostate cancer cells.
AB  - Aberrant coregulator expression that occurs during prostate cancer (PCa)
      progression correlates with poor prognosis and aggressive disease. This has been
      attributed to the ability to regulate androgen receptor-mediated transcription.
      We have shown previously that the androgenic milieu regulates the expression of
      the coactivators p300 and FHL2, with severe consequences for PCa cell
      proliferation and androgen receptor transcriptional activity. To determine the
      extent of androgen dependency of coregulator genes, we designed a cDNA-mediated
      annealing, selection, extension, and ligation RNA profiling array that probes the
      expression of 186 coregulators. Using this assay, we demonstrated androgen
      control over approximately 30% of coregulator genes in PCa cells. For a subset of
      15 functionally diverse coregulators, androgen regulation was confirmed using
      real-time RT-PCR and immunoblotting. The extent, dose dependency, and kinetics by
      which androgens affect coregulator expression differed widely, indicating diverse
      molecular mechanisms underlying these effects. Moreover, differences in
      coregulator expression were observed between isogenic androgen-dependent and
      castration-recurrent PCa cells. Small interfering RNA-mediated changes in
      coregulator expression had profound effects on cell proliferation, which were
      most pronounced in castration-recurrent cells. Taken together, our integrated
      approach combining expression profiling, characterization of androgen-dependent
      coregulator expression, and validation of the importance of altered coregulator
      expression for cell proliferation identified several potential novel therapeutic
      targets for PCa treatment.

PMID- 19164448
TI  - Loss of betaglycan contributes to the malignant properties of human granulosa
      tumor cells.
AB  - Betaglycan is a type III TGFbeta receptor that modulates cellular sensitivity to
      inhibins and TGFbeta. Previous studies have suggested that betaglycan acts as a
      tumor suppressor in certain human epithelial cancers. However, the roles of
      betaglycan in ovarian granulosa cell tumors (GCTs) are poorly understood. The
      objective of this study was to determine whether human GCTs exhibit betaglycan
      expression and, if so, what impact this receptor has on tumor biology. Real-time
      PCR was used to quantify betaglycan transcripts in human GCTs (n = 17) and normal
      premenopausal ovaries (n = 11). This analysis established that GCTs exhibited a
      significant 2-fold lower mean betaglycan mRNA level as compared with the normal
      ovary (P < 0.05). Similarly, two human GCT cell lines, KGN and COV434, exhibited
      low betaglycan expression and poor responsiveness to TGFbeta and inhibin A in
      luciferase reporter assays, which was restored by stable transfection of wild
      type betaglycan. Betaglycan significantly increased the adhesion of COV434 (P <
      0.05) and KGN (P < 0.0001) cells, decreased cellular invasion through Matrigel,
      and inhibited wound healing. Expression of mutant forms of betaglycan that are
      defective in TGFbeta and/or inhibin binding in each GCT cell line revealed that
      the inhibitory effects of betaglycan on wound healing were most strongly linked
      to the inhibin-binding region of betaglycan. Furthermore, knockdown of INHA mRNA
      expression abrogated the betaglycan-mediated inhibition of wound healing and
      invasion, whereas both INHA silencing and TGFbeta neutralization abolished the
      betaglycan-mediated increase in adhesion to substrate. These data suggest that
      loss of betaglycan contributes to the pathogenesis of GCTs.

PMID- 19164449
TI  - Insulin regulates TRB3 and other stress-responsive gene expression through
      induction of C/EBPbeta.
AB  - Pseudokinase TRB3 is an inducible gene whose expression is regulated by stress
      response and insulin and associated with insulin resistance and metabolic
      syndrome. In this report, we have investigated the mechanism under which insulin
      regulates TRB3 gene expression and demonstrated that insulin induces TRB3
      expression via C/EBPbeta. We found that in Fao hepatoma and 3T3-L1 adipocytes,
      C/EBPbeta expression induced by insulin preceded that of TRB3 and that mutation
      of the C/EBPbeta binding site in TRB3 promoter abolished the responsiveness of
      the TRB3 gene to insulin. We further showed that ectopic expression of C/EBPbeta
      augmented, whereas knockdown of C/EBPbeta reduced, TRB3 expression induced by
      insulin. In addition, we presented data to show that insulin, through a similar
      mechanism under which insulin induces TRB3 expression, promotes the expression of
      genes such as ANAS, ATF3, BIP, and CHOP, which are typical stress-responsive
      genes. We also examined the impact of C/EBPbeta expression on Akt activation and
      found that inaction of C/EBPbeta not only augmented Akt activation but also
      obliterated the suppression of Akt activation due to prolonged insulin
      stimulation. We suggest, through induction of C/EBPbeta in hepatic cells and
      adipocytes, that insulin induces the expression of stress-responsive genes, which
      may represent a novel insulin action.

PMID- 19164450
TI  - Susceptibility to autoimmunity and B cell resistance to apoptosis in mice lacking
      androgen receptor in B cells.
AB  - Estrogens have been linked to a higher female incidence of autoimmune diseases.
      The role of androgen and the androgen receptor (AR) in autoimmune diseases,
      however, remains unclear. Here we report that the lack of AR in B cells in
      different strains of mice, namely general AR knockout, B cell-specific AR
      knockout, and naturally occurring testicular feminization mutation AR-mutant
      mice, as well as castrated wild-type mice, results in increased B cells in blood
      and bone marrow. Analysis of the targeted mice, together with bone marrow
      transplantation using Rag1(-/-) recipients, overexpression of retrovirally
      encoded AR-cDNA, and small interfering RNA-mediated AR mRNA knockdown approaches
      also show that the B cell expansion results from resistance to apoptosis and
      increased proliferation of bone marrow precursor B cells, accompanied by changes
      in several key modulators related to apoptosis, such as Fas/FasL signals,
      caspases-3/-8, nuclear factor-kappaB, and Bcl-2. We also show that the effects of
      AR loss are, in part, B cell intrinsic. Mice bearing AR-deficient B cells show
      increased levels of serum IgG2a and IgG3 as well as basal double-stranded DNA-IgG
      antibodies and are more vulnerable to development of collagen-induced arthritis.
      Together, these data indicate that androgen/AR play a crucial role in B cell
      homeostasis and tolerance. Therapies targeting AR might provide an alternative
      strategy with which to battle autoimmune diseases.

PMID- 19164451
TI  - Alternative splicing of the murine receptor for advanced glycation end-products
      (RAGE) gene.
AB  - The alternative splicing of pre-mRNAs is a critical mechanism in genomic
      complexity, disease, and development. Studies of the receptor for advanced
      glycation end-products (RAGE) indicate that this gene undergoes a variety of
      splice events in humans. However, no studies have extensively analyzed the tissue
      distribution in other species or compared evolutionary differences of RAGE
      isoforms. Because the majority of studies probing RAGE function have been
      performed in murine models, we therefore performed studies to identify and
      characterize the splice variants of the murine RAGE gene, and we compared these
      to human isoforms. Here, using mouse tissues, we identified numerous splice
      variants including changes in the extracellular domain or the removal of the
      transmembrane and cytoplasmic domains, which produce soluble splice isoforms.
      Comparison of splice variants between humans and mice revealed homologous regions
      in the RAGE gene that undergo splicing as well as key species-specific mechanisms
      of splicing. Further analysis of tissue splice variant distribution in mice
      revealed major differences between lung, kidney, heart, and brain. To probe the
      potential impact of disease-like pathological states, we studied diabetic mice
      and report that RAGE splice variation changed dramatically, resulting in an
      increase in production of soluble RAGE (sRAGE) splice variants, which were not
      associated with detectable levels of sRAGE in murine plasma. In conclusion, we
      have determined that the murine RAGE gene undergoes extensive splicing with
      distinct splice isoforms being uniquely distributed in different tissues. These
      differences in RAGE splicing in both physiological and pathogenic states further
      expand our understanding of the biological repertoire of this receptor in health
      and disease.

PMID- 19164452
TI  - MGMT and MLH1 promoter methylation versus APC, KRAS and BRAF gene mutations in
      colorectal cancer: indications for distinct pathways and sequence of events.
AB  - BACKGROUND: To study how caretaker gene silencing relates to gatekeeper mutations
      in colorectal cancer (CRC), we investigated whether O6-methylguanine DNA
      methyltransferase (MGMT) and Human Mut-L Homologue 1 (MLH1) promoter
      hypermethylation are associated with APC, KRAS and BRAF mutations among 734 CRC
      patients. METHODS: We compared MGMT hypermethylation with G:C > A:T mutations in
      APC and KRAS and with the occurrence of such mutations in CpG or non-CpG
      dinucleotides in APC. We also compared MLH1 hypermethylation with truncating APC
      mutations and activating KRAS and BRAF mutations. RESULTS: Only 10% of the tumors
      showed both MGMT and MLH1 hypermethylation. MGMT hypermethylation occurred more
      frequently in tumors with G:C > A:T KRAS mutations (55%) compared with those
      without these mutations (38%, P < 0.001). No such difference was observed for G:C
      > A:T mutations in APC, regardless of whether mutations occurred in CpG or non
      CpG dinucleotides. MLH1 hypermethylation was less common in tumors with APC
      mutations (P = 0.006) or KRAS mutations (P = 0.001), but was positively
      associated with BRAF mutations (P < 0.001). CONCLUSIONS: MGMT hypermethylation is
      associated with G:C > A:T mutations in KRAS, but not in APC, suggesting that MGMT
      hypermethylation may succeed APC mutations but precedes KRAS mutations in
      colorectal carcinogenesis. MLH1-hypermethylated tumors harbor fewer APC and KRAS
      mutations and more BRAF mutations, suggesting that they develop distinctly from
      an MGMT methylator pathway.

PMID- 19164453
TI  - A comparison of models used to predict MLH1, MSH2 and MSH6 mutation carriers.
AB  - BACKGROUND: MMRpro, prediction of mutations in MLH1 and MLH2 (PREMM(1,2)) and
      MMRpredict are models which were developed to predict the probability that an
      individual carries a Lynch syndrome-causing mutation. Each model utilizes data
      from personal and family histories of cancer. To date, no studies have compared
      these models in a cancer genetics clinic. The purpose of this study was to
      determine each model's ability to predict the probability of carrying a Lynch
      syndrome-causing mutation in individuals with a family history of colorectal
      cancer and to determine their clinical applicability. METHODS: We obtained family
      pedigrees from 81 individuals who presented for Lynch syndrome testing due to a
      personal and/or family history of cancer. Data from each pedigree were entered
      into the models and analyzed using SPSS. RESULTS: We found that MMRpredict,
      PREMM(1,2) and MMRpro showed similar performances with areas under the receiver
      operating characteristic curve of 0.731, 0.765 and 0.732, respectively. MMRpro
      showed the least dispersion of mutation probability estimates with a P value of
      0.205, compared with 0.034 for PREMM(1,2) and 0.001 for MMRpredict. CONCLUSION:
      We found all three carried out well in a cancer genetics setting, with PREMM(1,2)
      giving slightly better estimates. There were some significant discrepancies
      between the models in cases where the proband had endometrial cancer.

PMID- 19164454
TI  - The impact of primary tumour origins in patients with advanced oesophageal,
      oesophago-gastric junction and gastric adenocarcinoma--individual patient data
      from 1775 patients in four randomised controlled trials.
AB  - BACKGROUND: It is unclear if differential chemotherapy effects exist on overall
      survival (OS), response rate (RR) and toxicity depending on primary tumour origin
      [oesophageal versus oesophago-gastric junction (OGJ) versus gastric
      adenocarcinoma]. PATIENTS AND METHODS: A total of 2110 patients were enrolled in
      four randomised controlled trials (RCTs) assessing fluoropyrimidine +/- platinum
      based chemotherapy. This analysis used individual patient data and restricted to
      patients with adenocarcinoma who received one or more dose of chemotherapy.
      Gastric origin was the control in comparisons of tumour origin. RESULTS: Of the
      2110 patients randomised, 1775 (84%) patients had adenocarcinoma with oesophageal
      (n = 485), OGJ (n = 457) and gastric (n = 833) origins. The median OS was 9.5
      months in oesophageal, 9.3 months in OGJ and 8.7 months in gastric cancer (P =
      0.68). RR was 44.1% in oesophageal, 41.1% in OGJ and 35.6% in gastric cancers (P
      = 0.11 and 0.27, respectively, compared with gastric cancer on multivariate
      analysis). Toxicity composite end point occurred in 46%, 47% and 45% in
      oesophageal, OGJ and gastric cancers, respectively (P = 0.85 and 0.62 compared
      with gastric). CONCLUSIONS: In our large multicentre RCT dataset, no significant
      differences were demonstrated on multivariate analyses in OS, RR and toxic
      effects among patients with advanced oesophageal, OGJ and gastric adenocarcinoma.
      Future RCTs should not exclude oesophageal adenocarcinoma.

PMID- 19164455
TI  - Prevalence, distress, management, and relief of pain during the last 3 months of
      cancer patients' life. Results of an Italian mortality follow-back survey.
AB  - BACKGROUND: This study estimates prevalence, management, and relief of pain
      during the last 3 months of life of a representative sample of dying cancer
      patients in Italy. PATIENTS AND METHODS: This is a mortality follow-back survey
      (the Italian Survey of the Dying of Cancer). Caregivers were interviewed, after
      the patient's death, about pain experienced by the patients in all settings of
      care. RESULTS: According to caregivers' reports, 82.3% [95% confidence interval
      (CI) 79.9% to 84.4%] patients experienced pain, and 61.0% (95% CI 57.9% to 64.0%)
      very distressing pain. The younger population experienced a higher prevalence of
      pain in respect to older patients (P < 0.01). Patients with tumors of the central
      nervous system experienced the lowest prevalence (51.9%). According to
      caregivers' reports, only 59.5% (95% CI 3.7% to 65.0%) received analgesic
      treatment with opioids for moderate to severe pain. Not surprisingly, pain was
      'only partially relieved' or 'not relieved at all' in 54% of the patients with
      very distressing pain. CONCLUSIONS: Although potentially slightly biased, the
      results from this survey regarding undermedication and poor treatment results for
      cancer related pain are unequivocal. The research agenda should focus on testing
      the effectiveness of interventions to improve the quality of pain assessment and
      management.

PMID- 19164456
TI  - Phase III trial of docetaxel plus gemcitabine versus docetaxel in second-line
      treatment for non-small-cell lung cancer: results of a Japan Clinical Oncology
      Group trial (JCOG0104).
AB  - BACKGROUND: This trial evaluated whether a combination of docetaxel and
      gemcitabine provides better survival than docetaxel alone in patients with
      previously treated non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:
      Eligibility included pathologically or cytologically proven NSCLC, failure of one
      platinum-based regimen, performance status of zero or one, 20-75 years old, and
      adequate organ function. Patients received docetaxel 60 mg/m(2) (day 1) or
      docetaxel 60 mg/m(2) (day 8) and gemcitabine 800 mg/m(2) (days 1 and 8), both
      administered every 21 days until disease progression. RESULTS: Sixty-five
      patients participated in each arm. This trial was terminated early due to an
      unexpected high incidence of interstitial lung disease (ILD) and three treatment
      related deaths due to ILD in the combination arm. Docetaxel plus gemcitabine
      compared with docetaxel-alone patients experienced similar grade and incidence of
      toxicity, except for ILD. No baseline factor was identified for predicting ILD.
      Median survival times were 10.3 and 10.1 months (one-sided P = 0.36) for
      docetaxel plus gemcitabine and docetaxel arms, respectively. CONCLUSION:
      Docetaxel alone is still the standard second-line treatment for NSCLC. The
      incidence of ILD is higher for docetaxel combined with gemcitabine than for
      docetaxel alone in patients with previously treated NSCLC.

PMID- 19164457
TI  - Antisense oligonucleotide targeting Bcl-2 messenger RNA in cancer: bad drug, bad
      target, neither or both?

PMID- 19164458
TI  - Early prediction of response to first-line chemotherapy by sequential [18F]-2
      fluoro-2-deoxy-D-glucose positron emission tomography in patients with advanced
      colorectal cancer.
AB  - BACKGROUND: To evaluate [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) positron
      emission tomography (PET), for early evaluation of response to palliative
      chemotherapy and for prediction of long-term outcome, in patients with metastatic
      colorectal cancer (mCRC). PATIENTS AND METHODS: In a randomized trial, patients
      with mCRC received irinotecan-based combination chemotherapy. FDG-PET was carried
      out before treatment and after two cycles in 51 patients at two centers. Visual
      changes in tumor FDG uptake and changes measured semi-automatically, as standard
      uptake values (SUVs), were compared with radiological response after four and
      eight cycles. RESULTS: The mean baseline SUV for all tumor lesions per patient
      was higher in nonresponders than in responders (mean 7.4 versus 5.6, P = 0.02).
      There was a strong correlation between metabolic response (changes in SUV) and
      objective response (r = 0.57, P = 0.00001), with a sensitivity of 77% and a
      specificity of 76%. There was no significant correlation between metabolic
      response and time to progression (P = 0.5) or overall survival (P = 0.1).
      CONCLUSIONS: Although metabolic response assessed by FDG-PET reflects
      radiological tumor volume changes, the sensitivity and specificity are too low to
      support the routine use of PET in mCRC. Furthermore, PET failed to reflect long
      term outcome and can, thus, not be used as surrogate end point for hard endpoint
      benefit.

PMID- 19164460
TI  - Eicosapentaenoic acid improves imbalance between vasodilator and vasoconstrictor
      actions of endothelium-derived factors in mesenteric arteries from rats at
      chronic stage of type 2 diabetes.
AB  - Accumulating evidence demonstrates that dietary intake of n-3 polyunsaturated
      fatty acids (PUFAs) is associated with a reduced incidence of several
      cardiovascular diseases that involve endothelial dysfunction. However, the
      molecular mechanism remains unclear. We previously reported that mesenteric
      arteries from type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats
      exhibit endothelial dysfunction, leading to an imbalance between endothelium
      derived vasodilators [namely, nitric oxide (NO) and endothelium-derived
      hyperpolarizing factor (EDHF)] and vasoconstrictors [endothelium-derived
      contracting factors (EDCFs)] [namely cyclooxygenase (COX)-derived prostanoids]
      (Am J Physiol Heart Circ Physiol 293:H1480-H1490, 2007). We hypothesized that
      treating OLETF rats with eicosapentaenoic acid (EPA), a major n-3 PUFA, may
      improve endothelial dysfunction by correcting this imbalance. In OLETF rats
      [compared with age-matched control Long-Evans Tokushima Otsuka (LETO) rats]: 1)
      acetylcholine (ACh)-induced (endothelium-dependent) relaxation was impaired, 2)
      NO- and EDHF-mediated relaxations and nitrite production were reduced, and 3) ACh
      induced EDCF-mediated contraction, production of prostanoids, and the protein
      expressions of COX-1 and COX-2 were all increased. When OLETF rats received
      chronic EPA treatment long-term (300 mg/kg/day p.o. for 4 weeks), their isolated
      mesenteric arteries exhibited: 1) improvements in ACh-induced NO- and EDHF
      mediated relaxations and COX-mediated contraction, 2) reduced EDCF- and
      arachidonic acid-induced contractions, 3) normalized NO metabolism, 4) suppressed
      production of prostanoids, 5) reduced COX-2 expression, and 6) reduced
      phosphoextracellular signal-regulated kinase (ERK) expression. Moreover, EPA
      treatment reduced both ERK2 and nuclear factor (NF)-kappaB activities in isolated
      OLETF aortas. We propose that EPA ameliorates endothelial dysfunction in OLETF
      rats by correcting the imbalance between endothelium-derived factors, at least
      partly, by inhibiting ERK, decreasing NF-kappaB activation, and reducing COX-2
      expression.

PMID- 19164459
TI  - Time-dependent association of total serum cholesterol and cancer incidence in a
      cohort of 172,210 men and women: a prospective 19-year follow-up study.
AB  - BACKGROUND: The relationship between serum cholesterol and cancer incidence
      remains controversial. PATIENTS AND METHODS: We investigated the association of
      total serum cholesterol (TSC) with subsequent cancer incidence in a population
      based cohort of 172 210 Austrian adults prospectively followed up for a median of
      13.0 years. Cox regression, allowing for time-dependent effects, was used to
      estimate adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for
      the association of TSC with cancer. RESULTS: We observed pronounced short-term
      associations of TSC and overall cancer incidence in both men and women. For
      malignancies diagnosed shortly (<5 months) after baseline TSC measurement, the
      highest TSC tertile (>235.0 mg/dl in men and >229.0 in women) compared with the
      lowest tertile (<194.0 mg/dl in men and <190.0 in women) was associated with a
      significantly lower overall cancer risk [HR = 0.58 (95% CI 0.43-0.78, P(trend) =
      0.0001) in men, HR = 0.69 (95% CI 0.49-0.99, P(trend) = 0.03) in women]. However,
      after roughly 5 months from baseline measurement, overall cancer risk was not
      significantly associated with TSC. The short-term inverse association of TSC with
      cancer was mainly driven by malignancies of the digestive organs and lymphoid and
      hematopoietic tissue. CONCLUSION: The short-term decrease of cancer risk seen for
      high levels of TSC may largely capture preclinical effects of cancer on TSC.

PMID- 19164461
TI  - Cyclooxygenase-dependent alterations in substance P-mediated contractility and
      tachykinin NK1 receptor expression in the colonic circular muscle of patients
      with slow transit constipation.
AB  - Tachykinins are important neurotransmitters regulating intestinal motility. Slow
      transit constipation (STC) represents an extreme colonic dysmotility with unknown
      etiology that predominantly affects women. We examined whether the tachykinin
      system is involved in the pathogenesis of STC. Isolated sigmoid colon circular
      muscle from female STC and control patients was studied using functional and
      quantitative reverse transcriptase-polymerase chain reaction methods. A possible
      alteration of neurotransmission was investigated by electrical field stimulation
      (EFS) and ganglionic stimulation by dimethylphenylpiperazinium (DMPP). Substance
      P (SP)-mediated contractions in circular muscle strips were significantly
      diminished in STC compared with age-matched control (P < 0.001). In contrast,
      contractile responses to neurokinin A, the selective tachykinin NK(2) receptor
      agonist, [Lys(5),MeLeu(9),Nle(10)]NKA(4-10), and acetylcholine were unaltered in
      STC. The reduced responses to SP in STC were fully restored by indomethacin,
      partially reversed by tetrodotoxin (TTX), but unaffected by atropine or
      hexamethonium. The restoration by indomethacin was blocked by the NK(1) receptor
      antagonist CP99994 [(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine] and TTX.
      In STC colonic muscle, there was a significant increase of NK(1) receptor mRNA
      expression, but no difference in NK(2) mRNA level. DMPP generated biphasic
      responses, relaxation at lower and contraction at higher concentrations. Although
      the responses to DMPP were similar in STC and control, an altered contractile
      pattern in response to EFS was observed in STC circular muscle. In conclusion, we
      postulate that the diminished contractile response to SP in STC is due to an
      increased release of inhibitory prostaglandins through activation of up-regulated
      NK(1) receptors. Our results also indicate some malfunction of the enteric
      nervous system in STC.

PMID- 19164462
TI  - Involvement of human multidrug and toxin extrusion 1 in the drug interaction
      between cimetidine and metformin in renal epithelial cells.
AB  - In human proximal tubules, organic cations are taken up from blood into cells by
      human organic cation transporter 2 [hOCT2/solute carrier (SLC) 22A2] and then
      eliminated into the lumen by apical H(+)/organic cation antiporters, human
      multidrug and toxin extrusion 1 (hMATE1/SLC47A1) and hMATE2-K (SLC47A2). To
      evaluate drug interactions of cationic drugs in the secretion process, epithelial
      cells engineered to express both hOCT2 and hMATE transporters are required to
      simultaneously evaluate drug interactions with renal basolateral and apical
      organic cation transporters. In the present study, therefore, we assessed the
      drug interaction between cimetidine and metformin with double-transfected Madin
      Darby canine kidney cells stably expressing both hOCT2 and hMATE1 as an in vitro
      model of the proximal tubular epithelial cells. The basolateral-to-apical
      transport and intracellular accumulation of [(14)C]metformin by a double
      transfectant were markedly inhibited by 1 mM cimetidine at the basolateral side.
      On the other hand, 1 microM cimetidine at the basolateral side moderately
      decreased the basolateral-to-apical transport of [(14)C]metformin and
      significantly increased the intracellular accumulation of [(14)C]metformin from
      the basolateral side, suggesting that cimetidine at a low concentration inhibits
      apical hMATE1, rather than basolateral hOCT2. Actually, in concentration
      dependent inhibition studies by a single transporter expression system, such as
      human embryonic kidney 293 stably expressing hMATE1, hMATE2-K, or hOCT2,
      cimetidine showed higher affinity for hMATEs than for hOCT2. These results
      suggest that apical hMATE1 is involved in drug interactions between cimetidine
      and cationic compounds in the proximal tubular epithelial cells.

PMID- 19164463
TI  - The role of the equilibrative nucleoside transporter 1 (ENT1) in transport and
      metabolism of ribavirin by human and wild-type or Ent1-/- mouse erythrocytes.
AB  - The polar nucleoside drug ribavirin is front-line treatment for chronic hepatitis
      C virus infection. The human equilibrative nucleoside transporter (ENT) 1
      transports ribavirin into erythrocytes where it is phosphorylated. These
      phosphorylated metabolites accumulate in the erythrocytes and produce dose
      limiting hemolytic anemia. Here, we examined the in vitro and ex vivo transport
      and metabolism of ribavirin by erythrocytes isolated from humans and Ent1-null
      mice. Ribavirin (2.4 microM) uptake was significantly higher (1044 +/- 255
      amol/microg/10 s) into erythrocytes from Ent1(+/+) mice compared with that from
      Ent1(-/-) mice (76.48 +/- 11.20 amol/microg/10 s). Our results showed a saturable
      (K(m) of 382 +/- 75.1 microM) transport of [(3)H]ribavirin into erythrocytes from
      Ent1(+/+) mice. We found that ribavirin concentration rapidly (within 60 s)
      reached equilibrium in erythrocytes using a time course of [(3)H]ribavirin
      transport (2.5 microM) and metabolism in mouse and human erythrocytes for 8 h.
      However, total radioactivity of ribavirin was predominantly attributed to the
      phosphorylated metabolites ribavirin monophosphate and ribavirin triphosphate.
      Our findings allow us to estimate ribavirin transport, diffusion, and metabolic
      clearance and to predict in vivo accumulation of ribavirin phosphates in
      erythrocytes of both mice and humans. Our modeling of ribavirin in erythrocytes
      on long-term administration of ribavirin suggests that the accumulation of
      ribavirin inside the cells is dependent on ENT1/Ent1 transport and the rates of
      intracellular phosphorylation and the degradation of the phosphorylated
      metabolites. We predict that Ent1(+/+) and Ent1(-/-) mice will serve as excellent
      models to investigate the contribution of Ent1 to the pharmacokinetics and
      toxicity of ribavirin in vivo.

PMID- 19164464
TI  - Substrate selectivity of 5-hydroxyeicosanoid dehydrogenase and its inhibition by
      5-hydroxy-Delta6-long-chain fatty acids.
AB  - 5-Oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) is a metabolite of the 5
      lipoxygenase (5-LO) product 5S-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5
      HETE), formed by the microsomal enzyme 5-hydroxyeicosanoid dehydrogenase (5
      HEDH). 5-oxo-ETE is a chemoattractant for neutrophils and eosinophils, both in
      vitro and in vivo. To examine the substrate selectivity of 5-HEDH and to search
      for potential inhibitors, we prepared a series of 5S-hydroxy fatty acids (C(12)
      to C(20) containing zero to four double bonds) by total chemical synthesis and
      examined their metabolism by microsomes from monocytic U937 cells. Although most
      of these fatty acids were oxidized to their 5-oxo metabolites by 5-HEDH, 5-HETE
      seemed to be the best substrate. However, substrates containing less than 16
      carbons, a methylated alpha-carboxyl group, or a hydroxyl group at the omega-end
      of the molecule were not substantially metabolized. Some of the fatty acids
      tested were fairly potent inhibitors of the formation of 5-oxo-ETE by 5-HEDH, in
      particular 5-hydroxy-6-octadecenoic acid and 5-hydroxy-6-eicosenoic acid. Both
      substances selectively inhibited 5-oxo-ETE formation by human peripheral blood
      mononuclear cells incubated with arachidonic acid and calcium ionophore without
      affecting the formation of leukotriene B(4), 12-HETE, or 12-hydroxy-5,8,10
      heptadecatrienoic acid. We conclude that the requirements for appreciable
      metabolism by 5-HEDH include a chain length of at least 16 carbons, a free alpha
      carboxyl group, and a hydrophobic group at the omega-end of the molecule. 5
      Hydroxy-Delta(6) C(18) and C(20) fatty acids selectively inhibit 5-HEDH without
      inhibiting 5-LO, leukotriene A(4) hydrolase, 12-lipoxygenase, or cyclooxygenase.
      Such compounds may be useful in defining the role of 5-oxo-ETE and its mechanism
      of synthesis.

PMID- 19164465
TI  - Cytisine-based nicotinic partial agonists as novel antidepressant compounds.
AB  - Nicotine and other nicotinic agents are thought to regulate mood in human
      subjects and have antidepressant-like properties in animal models. Recent studies
      have demonstrated that blockade of nicotinic acetylcholine receptors (nAChRs)
      including those containing the beta2 subunit (beta2(*)), results in
      antidepressant-like effects. Previous studies have shown that cytisine, a partial
      agonist at alpha4/beta2(*) nAChRs, and a full agonist at alpha3/beta4(*) and
      alpha7 nAChRs, has antidepressant-like properties in several rodent models of
      antidepressant efficacy; however, it is not clear whether more selective partial
      agonists will also be effective in these models. We tested cytisine and two
      derivatives, 5-bromo-cytisine (5-Br-Cyt) and 3-(pyridin-3'-yl)-cytisine (3-pyr
      Cyt) for their ability to act as a partial agonist of different nAChR subtypes
      and to show antidepressant-like activity in C57/BL6 mice in the tail suspension,
      the forced-swim, and the novelty-suppressed feeding tests. 3-pyr-Cyt was a
      partial agonist with very low efficacy at alpha4/beta2(*) nAChRS but had no
      agonist effects at other nAChRs normally targeted by cytisine, and it was
      effective in mouse models of antidepressant efficacy. Animals showed dose
      dependent antidepressant-like effects in all three behavioral paradigms. 5-Br-Cyt
      was not effective in behavioral tests when administered peripherally, probably
      because of its inability to penetrate the blood-brain barrier, because it
      efficiently reduced immobility in the tail suspension test when administered
      intraventricularly. These results suggest that novel nicotinic partial agonists
      may provide new possibilities for development of drugs to treat mood disorders.

PMID- 19164466
TI  - Identification of human CYP2C8 as a retinoid-related orphan nuclear receptor
      target gene.
AB  - Retinoid-related orphan nuclear receptors (RORs) alpha and gamma (NR1F1, -3) are
      highly expressed in liver, adipose tissue, thymus, and brain and are involved in
      many physiological processes, such as circadian rhythm and immune function.
      Enzymes in the cytochrome P450 2C subfamily metabolize many clinically important
      drugs and endogenous compounds, such as the anticancer drug paclitaxel and
      arachidonic acid, and are highly expressed in liver. Here, we present the first
      evidence that RORs regulate the transcription of human CYP2C8. Overexpression of
      RORalpha and RORgamma in HepG2 cells significantly enhanced the activity of the
      CYP2C8 promoter but not that of the CYP2C9 or CYP2C19 promoters. Computer
      analyses, promoter deletion studies, gel shift assays, and mutational analysis
      identified an essential ROR-responsive element at -2045 base pairs in the CYP2C8
      promoter that mediates ROR transactivation. Adenoviral overexpression of RORalpha
      and -gamma significantly induced endogenous CYP2C8 transcripts in both HepG2
      cells and human primary hepatocytes. Knockdown of endogenous RORalpha and -gamma
      expression in HepG2 cells by RNA interference decreased the expression of
      endogenous CYP2C8 mRNA by approximately 50%. These data indicate that RORs
      transcriptionally up-regulate CYP2C8 in human liver and, therefore, may be
      important modulators of the metabolism of drugs and physiologically active
      endogenous compounds by this enzyme in liver and possibly extrahepatic tissues
      where RORs are expressed.

PMID- 19164467
TI  - Torcetrapib induces aldosterone and cortisol production by an intracellular
      calcium-mediated mechanism independently of cholesteryl ester transfer protein
      inhibition.
AB  - ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in
      Atherosclerotic Events), the phase 3 morbidity and mortality trial of
      torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, identified
      previously undescribed changes in plasma levels of potassium, sodium,
      bicarbonate, and aldosterone. A key question after this trial is whether the
      failure of torcetrapib was a result of CETP inhibition or of some other
      pharmacology of the molecule. The direct effects of torcetrapib and related
      molecules on adrenal steroid production were assessed in cell culture using the
      H295R as well as the newly developed HAC15 human adrenal carcinoma cell lines.
      Torcetrapib induced the synthesis of both aldosterone and cortisol in these two
      in vitro cell systems. Analysis of steroidogenic gene expression indicated that
      torcetrapib significantly induced the expression of CYP11B2 and CYP11B1, two
      enzymes in the last step of aldosterone and cortisol biosynthesis pathway,
      respectively. Transcription profiling indicated that torcetrapib and angiotensin
      II share overlapping pathways in regulating adrenal steroid biosynthesis. Hormone
      induced steroid production is mainly mediated by two messengers, calcium and
      cAMP. An increase of intracellular calcium was observed after torcetrapib
      treatment, whereas cAMP was unchanged. Consistent with intracellular calcium
      being the key mediator of torcetrapib's effect in adrenal cells, calcium channel
      blockers completely blocked torcetrapib-induced corticoid release and calcium
      increase. A series of compounds structurally related to torcetrapib as well as
      structurally distinct compounds were profiled. The results indicate that the
      pressor and adrenal effects observed with torcetrapib and related molecules are
      independent of CETP inhibition.

PMID- 19164468
TI  - The orexigenic activity of the hypothalamic neuropeptide 26RFa is mediated by the
      neuropeptide Y and proopiomelanocortin neurons of the arcuate nucleus.
AB  - 26RFa is a hypothalamic RFamide neuropeptide that was identified as the
      endogenous ligand of the orphan G protein-coupled receptor, GPR103, and that
      stimulates appetite in mice. Up until now, the mechanism of action of 26RFa in
      the hypothalamic control of food intake remains unknown. The high density of
      GPR103 in the arcuate nucleus (Arc) prompted us to investigate, in the present
      study, the effects of 26RFa on the rat neuropeptide Y (NPY)/proopiomelanocortin
      (POMC) system. Intracerebroventricular injection of 26RFa stimulated NPY
      expression and release in the basal hypothalamus, whereas it decreased POMC
      expression and alpha-MSH release, and these effects were associated with an
      increase in food intake. A double in situ hybridization procedure indicated that
      the 26RFa receptor is present in NPY neurons of the Arc, but not in POMC neurons.
      Central administration of NPY Y1 and Y5 receptor antagonists abolished the
      inhibitory effects of 26RFa on POMC expression and alpha-MSH release, and
      reversed 26RFa-induced food consumption. Finally, 26RFa antagonized the effects
      of leptin on NPY expression and release, POMC expression and alpha-MSH release,
      and food intake. Altogether, the present data demonstrate for the first time that
      26RFa exerts its orexigenic activity by stimulating the release of NPY in the
      Arc, which in turn inhibits POMC neurons by activating the Y1 and Y5 receptors.
      It is also suggested that the balance 26RFa/leptin is an important parameter in
      the maintenance of energy homeostasis.

PMID- 19164469
TI  - 1Alpha,25-dihydroxyvitamin D3 reduces c-Myc expression, inhibiting proliferation
      and causing G1 accumulation in C4-2 prostate cancer cells.
AB  - There is an inverse correlation between exposure to sunlight (the major source of
      vitamin D) and the risk for prostate cancer, the most common noncutaneous cancer
      and second most common cause of death from cancer in American men. The active
      metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] acting
      through the vitamin D receptor decreases prostate cancer cell growth and
      invasiveness. The precise mechanisms by which 1,25(OH)(2)D(3) inhibits growth in
      prostate cancer have not been fully elucidated. Treatment with 1,25(OH)(2)D(3)
      causes an accumulation in the G(0)/G(1) phase of the cell cycle in several
      prostate cancer cell lines. One potential target known to regulate the G(0)/G(1)
      to S phase transition is c-Myc, a transcription factor whose overexpression is
      associated with a number of cancers including prostate cancer. We find that
      1,25(OH)(2)D(3) reduces c-Myc expression in multiple prostate epithelial cell
      lines, including C4-2 cells, an androgen-independent prostate cancer cell line.
      Reducing c-Myc expression to the levels observed after 1,25(OH)(2)D(3) treatment
      resulted in a comparable decrease in proliferation and G(1) accumulation
      demonstrating that down-regulation of c-Myc is a major component in the growth
      inhibitory actions of 1,25(OH)2D(3). Treatment with 1,25(OH)(2)D(3) resulted in a
      50% decrease in c-Myc mRNA but a much more extensive reduction in c-Myc protein.
      Treatment with 1,25(OH)(2)D(3) decreased c-Myc stability by increasing the
      proportion of c-Myc phosphorylated on T58, a glycogen synthase kinase-3beta site
      that serves as a signal for ubiquitin-mediated proteolysis. Thus, 1,25(OH)(2)D(3)
      reduces both c-Myc mRNA levels and c-Myc protein stability to inhibit growth of
      prostate cancer cells.

PMID- 19164471
TI  - The identification of a calmodulin-binding domain within the cytoplasmic tail of
      angiotensin-converting enzyme-2.
AB  - Angiotensin-converting enzyme (ACE)-2 is a homolog of the well-characterized
      plasma membrane-bound angiotensin-converting enzyme. ACE2 is thought to play a
      critical role in regulating heart function, and in 2003, ACE2 was identified as a
      functional receptor for severe acute respiratory syndrome coronavirus. We have
      recently shown that like ACE, ACE2 undergoes ectodomain shedding and that this
      shedding event is up-regulated by phorbol esters. In the present study, we used
      gel shift assays to demonstrate that calmodulin, an intracellular calcium-binding
      protein implicated in the regulation of other ectodomain shedding events, binds a
      16-amino acid synthetic peptide corresponding to residues 762-777 within the
      cytoplasmic domain of human ACE2, forming a calcium-dependent calmodulin-peptide
      complex. Furthermore, we have demonstrated that ACE2 expressed in Chinese hamster
      ovary cells specifically binds to glutathione-S-transferase-calmodulin, but not
      glutathione-S-transferase alone, in pull-down assays using cell lysates. Finally,
      to investigate whether calmodulin has any effect on ACE2 ectodomain shedding in
      cells that endogenously express the enzyme, cells from a human liver cell line
      (Huh-7) expressing ACE2 were incubated with calmodulin-specific inhibitors,
      trifluoperazine and calmidazolium. Both trifluoperazine (25 micromol/liter) and
      calmidazolium, (25 micromol/liter) significantly increased the release of ACE2
      into the medium (44.1 +/- 10.8%, P < 0.05, Student's t test; unpaired, two
      tailed, and 51.1 +/- 7.4% P < 0.05, one-way ANOVA, respectively;), as analyzed by
      an ACE2-specific quenched fluorescence substrate assay. We also show that the
      calmodulin-specific inhibitor-stimulated shedding of ACE2 is independent from
      phorbol ester-induced shedding. In summary, we have demonstrated that calmodulin
      is able to bind ACE2 and suggest that the ACE2 ectodomain shedding and/or
      sheddase(s) activation regulated by calmodulin is independent from the phorbol
      ester-induced shedding.

PMID- 19164470
TI  - Gamma-aminobutyric acid B receptor mediated inhibition of gonadotropin-releasing
      hormone neurons is suppressed by kisspeptin-G protein-coupled receptor 54
      signaling.
AB  - Gamma-aminobutyric acid (GABA) is one of the most important neurotransmitters
      that regulate the excitability of GnRH neurons. Numerous studies have shown that
      GABA activates Cl(-) currents in GnRH neurons, and these effects are antagonized
      by GABA(A) receptor antagonists. The GABA(B) receptor is a heterodimer composed
      of GABA(B) R1 and R2, and although both subunits have been localized in GnRH
      neurons, nothing is known about the cellular signaling of this G alpha(i,o)
      coupled receptor in GnRH neurons. Using whole-cell recordings from mouse enhanced
      green fluorescent protein-GnRH neurons, we found that the GABA(B) receptor
      agonist baclofen hyperpolarized GnRH neurons through activation of an inwardly
      rectifying K(+) current in a concentration-dependent manner. The effects of
      baclofen were antagonized by the selective GABA(B) receptor antagonist CGP 52432
      with a K(i) (inhibitory constant) of 85 nm. Furthermore, in the presence of the
      GABA(A) receptor antagonist picrotoxin, GABA hyperpolarized GnRH neurons in a
      similar manner. Treatment with 17beta-estradiol as compared with oil vehicle did
      not significantly alter either the EC(50) for the baclofen-induced response (0.8
      +/- 0.1 vs. 1.0 +/- 0.1 microM, respectively) or the maximal outward current
      (10.8 +/- 1.7 pA vs. 11.4 +/- 0.6 pA, respectively) in GnRH neurons. However, the
      outward current (and membrane hyperpolarization) was abrogated by submaximal
      concentrations of the G protein-coupled receptor 54 (GPR54) agonist kisspeptin-10
      in both groups, indicating that G alpha(q)-coupled (GPR54) can desensitize the
      GABA(B) receptor-mediated response. Therefore, the activation of GABA(B)
      receptors in GnRH neurons may provide increased inhibitory tone during estrogen
      negative feedback states that is attenuated by kisspeptin during positive
      feedback.

PMID- 19164472
TI  - Opposite effects of interleukin-1alpha and transforming growth factor-beta2
      induce stage-specific regulation of junctional adhesion molecule-B gene in
      Sertoli cells.
AB  - In the mammalian testis, junctional adhesion molecule-B (JAM-B) is found at the
      blood-testis barrier between Sertoli cells and the apical ectoplasmic
      specializations between Sertoli and germ cells. The expression of JAM-B is
      tightly regulated to allow the transit of developing germ cells across the blood
      testis barrier and the timely release of mature spermatids at stage VIII. In this
      study, the basal transcription of JAM-B in the mouse Sertoli cell line, MSC-1
      cells, was examined. We found that the constitutive expression of JAM-B is
      carried out by the binding of specificity proteins (Sps), ETS domain
      transcription factor Elk-1 (Elk1), neuron-restrictive silencer factor (NRSF), and
      E2F transcription factor 3 (E2F3) to various cis-acting elements including TG
      interacting factor (TGIF), Elk-1, NRSF, and proximal Sp1 (pSp1) + E2F binding
      motifs. We also investigated the effects of two cytokines IL-1alpha and TGF-beta2
      on JAM-B expression. IL-1alpha promotes JAM-B expression by facilitating the
      binding of Elk-1 to TGIF and pSp1 + E2F motifs in a p38-dependent manner, which
      leads to an additive effect on Sp1- and NRSF-mediated JAM-B transactivation. TGF
      beta2 inhibits JAM-B transcription via the activation of mothers against
      decapentaplegic (Smad) proteins and activated Smads compete with specificity
      proteins (Sp1 and Sp3) for the TGIF motif, resulting in JAM-B repression. IL
      1alpha and Smad3 expression have been reported to be stage specific. IL-1alpha is
      absent in the seminferous epithelium at stages VII-VIII, whereas a high level of
      nuclear Smad3 level is found at the same stages. This study shows for the first
      time that IL-1alpha and TGF-beta2 regulate JAM-B expression in an opposite
      manner, and in vitro data obtained herein provide some clues on how junctions are
      regulated in the testis.

PMID- 19164473
TI  - Estrogens protect against high-fat diet-induced insulin resistance and glucose
      intolerance in mice.
AB  - Although corroborating data indicate that estrogens influence glucose metabolism
      through the activation of the estrogen receptor alpha (ERalpha), it has not been
      established whether this pathway could represent an effective therapeutic target
      to fight against metabolic disturbances induced by a high-fat diet (HFD). To this
      end, we first evaluated the influence of chronic 17beta-estradiol (E2)
      administration in wild-type ovariectomized mice submitted to either a normal chow
      diet or a HFD. Whereas only a modest effect was observed in normal chow diet-fed
      mice, E2 administration exerted a protective effect against HFD-induced glucose
      intolerance, and this beneficial action was abolished in ERalpha-deficient mice.
      Furthermore, E2 treatment reduced HFD-induced insulin resistance by 50% during
      hyperinsulinemic euglycemic clamp studies and improved insulin signaling (Akt
      phosphorylation) in insulin-stimulated skeletal muscles. Unexpectedly, we found
      that E2 treatment enhanced cytokine (IL-6, TNF-alpha) and plasminogen activator
      inhibitor-1 mRNA expression induced by HFD in the liver and visceral adipose
      tissue. Interestingly, although the proinflammatory effect of E2 was abolished in
      visceral adipose tissue from chimeric mice grafted with bone marrow cells from
      ERalpha-deficient mice, the beneficial effect of the hormone on glucose tolerance
      was not altered, suggesting that the metabolic and inflammatory effects of
      estrogens can be dissociated. Eventually comparison of sham-operated with
      ovariectomized HFD-fed mice demonstrated that endogenous estrogens levels are
      sufficient to exert a full protective effect against insulin resistance and
      glucose intolerance. In conclusion, the regulation of the ERalpha pathway could
      represent an effective strategy to reduce the impact of high-fat diet-induced
      type 2 diabetes.

PMID- 19164474
TI  - Inhibition of protein tyrosine phosphatase-1B with antisense oligonucleotides
      improves insulin sensitivity and increases adiponectin concentrations in monkeys.
AB  - Protein tyrosine phosphatase (PTP)-1B antagonizes insulin signaling and is a
      potential therapeutic target for insulin resistance associated with obesity and
      type 2 diabetes. To date, studies of PTP-1B have been limited by the availability
      of specific antagonists; however, treatment of rodents with antisense
      oligonucleotides (ASOs) directed against PTP-1B improves insulin sensitivity,
      inhibits lipogenic gene expression, and reduces triglyceride accumulation in
      liver and adipose tissue. Here we investigated ASO-mediated PTP-1B inhibition in
      primates. First, PTP-1B ASO (ISIS 113715) dose-dependently inhibited PTP-1B mRNA
      and protein expression in cultured monkey hepatocytes. Subcutaneous
      administration of ISIS 113715 reduced PTP-1B mRNA expression in liver and adipose
      tissue of normal-weight monkeys by 40-50% and improved insulin sensitivity during
      an iv glucose tolerance test (IVGTT). In obese, insulin-resistant rhesus monkeys,
      treatment with 20 mg/kg ISIS 113715 for 4 wk reduced fasting concentrations of
      insulin and glucose and reduced insulin responses during an IVGTT. In these
      animals, adiponectin concentrations were also increased by 70%, most of which was
      an increase of high-molecular-weight oligomers. These effects were not observed
      in monkeys on a lower, dose-escalation regimen (1-10 mg/kg over 9 wk). Overall,
      the increase of adiponectin concentrations during ISIS 113715 treatment was
      correlated with the lowering of insulin responses during IVGTT (r = -0.47, P =
      0.042). These results indicate that inhibition of PTP-1B with ASOs such as ISIS
      113715 may be a viable approach for the treatment and prevention of obesity
      associated insulin resistance and type 2 diabetes because they potently increase
      adiponectin concentrations in addition to improving insulin sensitivity.

PMID- 19164475
TI  - Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in
      vertebrates.
AB  - Kisspeptin and its receptor GPR54 play important roles in mammalian reproduction
      and cancer metastasis. Because the KiSS and GPR54 genes have been identified in a
      limited number of vertebrate species, mainly in mammals, the evolutionary history
      of these genes is poorly understood. In the present study, we have cloned
      multiple forms of kisspeptin and GPR54 cDNAs from a variety of vertebrate
      species. We found that fish have two forms of kisspeptin genes, KiSS-1 and KiSS
      2, whereas Xenopus possesses three forms of kisspeptin genes, KiSS-1a, KiSS-1b,
      and KiSS-2. The nonmammalian KiSS-1 gene was found to be the ortholog of the
      mammalian KiSS-1 gene, whereas the KiSS-2 gene is a novel form, encoding a C
      terminally amidated dodecapeptide in the Xenopus brain. This study is the first
      to identify a mature form of KiSS-2 product in the brain of any vertebrate.
      Likewise, fish possess two receptors, GPR54-1 and GPR54-2, whereas Xenopus carry
      three receptors, GPR54-1a, GPR54-1b, and GPR54-2. Sequence identity and genome
      synteny analyses indicate that Xenopus GPR54-1a is a human GPR54 ortholog,
      whereas Xenopus GPR54-1b is a fish GPR54-1 ortholog. Both kisspeptins and GPR54s
      were abundantly expressed in the Xenopus brain, notably in the hypothalamus,
      suggesting that these ligand-receptor pairs have neuroendocrine and
      neuromodulatory roles. Synthetic KiSS-1 and KiSS-2 peptides activated GPR54s
      expressed in CV-1 cells with different potencies, indicating differential ligand
      selectivity. These data shed new light on the molecular evolution of the
      kisspeptin-GPR54 system in vertebrates.

PMID- 19164477
TI  - Oxytocin pretreatment decreases oxytocin-induced myometrial contractions in
      pregnant rats in a concentration-dependent but not time-dependent manner.
AB  - Recent biomolecular studies have shown that continuous exposure of human
      myometrial cells to oxytocin results in a significant loss of responsiveness to
      subsequent oxytocin stimulation, perhaps because of desensitization of the
      oxytocin receptors. However, it is unclear whether this phenomenon results in a
      reduction of the contractile activity of the uterine muscle in humans or animals.
      The objective of our study was to investigate the in vitro response of the
      uterine muscle of pregnant rats to oxytocin, following preexposure to varying
      concentrations of oxytocin, for varying durations. Longitudinal myometrial strips
      were isolated from 16 pregnant Wistar rats at 19 to 21 days of gestation and
      preexposed to oxytocin 10(-10) or 10(-8) mol/L (experimental groups) or
      physiological salt solution (control groups) for 1- or 4-hour period. All muscle
      strips were then subjected to a dose-response study with oxytocin 10(-10) to 10(
      5) mol/L. The area under the curve, frequency, and amplitude of contractions were
      recorded and compared between the groups. The area under the curve, frequency,
      and amplitude of the oxytocin-induced contractions were all significantly
      suppressed in the groups preexposed to oxytocin 10(-8) mol/L compared to either
      the control groups (P < .0001) or the groups preexposed to oxytocin 10(-10) mol/L
      (P < .0001). There was no difference in the oxytocin-induced myometrial
      contractions between the groups preexposed to oxytocin for either the 1- or 4
      hour periods. The inhibition of the oxytocin-induced contractile response of
      pregnant rat myometrium is observed as early as 1 hour of preexposure to oxytocin
      and is dependent on the preexposed oxytocin concentration and not on the duration
      of its exposure.

PMID- 19164476
TI  - Mechanisms of leukocyte accumulation and activation in chorioamnionitis:
      interleukin 1 beta and tumor necrosis factor alpha enhance colony stimulating
      factor 2 expression in term decidua.
AB  - Chorioamnionitis is a major cause of prematurity as well as perinatal morbidity
      and mortality. The present study observed a marked increase in
      immunohistochemical staining for Colony Stimulating Factor 2 (CSF2; also known as
      granulocyte macrophage-colony stimulating factor), a potent neutrophil and
      macrophage chemoattractant and activator, in the decidua of patients with CAM
      compared with controls (n = 8; P = .001). To examine the regulation of this CSF2,
      cultured decidual cells primed with estradiol (E2) or E2 plus medroxyprogesterone
      acetate, were exposed to tumor necrosis factor-alpha or interleukin-1beta and
      secreted CSF2 measured by ELISA. Levels of CSF2 in E2 plus MPA-treated cultures
      increased 18- and 245-fold following treatment with TNF or IL1B (n = 7, P < .05).
      Quantitative RT-PCR demonstrated parallel changes in mRNA levels. This study
      reveals that CSF2 is strongly expressed in decidua from patients with CAM and
      indicates TNF or IL1B as important regulators of CAM-related decidual leukocyte
      infiltration and activation.

PMID- 19164478
TI  - Maternal progesterone treatment rescues the mammary impairment following
      uteroplacental insufficiency and improves postnatal pup growth in the rat.
AB  - Uteroplacental insufficiency in the rat reduces maternal progesterone and impairs
      mammary function and pup milk intake, compromising postnatal growth. We
      determined whether progesterone administration to rat dams progesterone-deficient
      following uteroplacental insufficiency improves lactation and pup growth.
      Uteroplacental insufficiency (Restriction) or sham surgery (Control) was
      performed on day 18 of pregnancy in WKY rats. Pregnant dams were injected with
      progesterone or vehicle, and Control mothers with vehicle for three days and
      killed on day 20 of pregnancy or day 6 of lactation. Progesterone treatment in
      the Restricted group restored maternal progesterone with no effect on mammary Pgr
      mRNA expression. Uteroplacental insufficiency triggered early lactogenesis, with
      increased mammary Csn2, Lalba and Wap mRNA. Progesterone treatment following
      uteroplacental insufficiency increased mammary alveolar number and area. Pups
      from progesterone treated mothers had increased body weight when compared to
      Controls. Overall, maternal progesterone treatment following uteroplacental
      insufficiency improved postnatal growth by rescuing the mammary impairment.

PMID- 19164479
TI  - Predominance of local over systemic factors in uterine arterial remodeling during
      pregnancy.
AB  - This study used a rat model in which pregnancy was surgically restricted to one
      uterine horn to differentiate between local (fetoplacental) and systemic
      (endocrine) influences on uterine vascular remodeling during pregnancy. Sprague
      Dawley rats with single-horn pregnancies were studied on day 20/22 of gestation
      and compared to age-matched nonpregnant and late-pregnant controls. The
      morphology (axial length, lumen diameter, wall thickness) of the main uterine
      artery and of smaller arcuate vessels showed that vascular growth was
      dramatically increased in the pregnant versus nonpregnant horn, (P < .05).
      Arcuate artery wall thickness increased in the nonpregnant horn (compared to
      nonpregnant controls, P < .05), suggesting a limited role for systemic hormonal
      influences on vascular remodeling. Notably, animals with only one functional horn
      compensated by increasing the average number of implantation sites per horn from
      7.6 to 12.9, thereby maintaining essentially normal litter size without any
      reduction in fetal or placental weights. These results demonstrate unequivocally
      that local rather than systemic influences play the dominant role in uterine
      vascular gestational remodeling of both large and small uterine arteries, and
      reveal a significant adaptive process that maintains relatively normal fecundity
      in spite of surgical restriction of normal bilateral pregnancy.

PMID- 19164480
TI  - The vasoactive peptide angiotensin-(1-7), its receptor Mas and the angiotensin
      converting enzyme type 2 are expressed in the human endometrium.
AB  - Angiotensin (Ang)-(1-7) is one of the major active components of the renin
      angiotensin system, produced from cleavage of Ang II by angiotensin-converting
      enzyme type 2 (ACE2), which acts through a specific G protein-coupled receptor,
      Mas. We have investigated whether the human endometrium expresses these
      components during menstrual cycle. By radioimmunoassay, Ang-(1-7) was detected in
      endometrial wash fluid at picomolar concentrations. Using immunofluorescence,
      both the peptide and its receptor were identified in cultured endometrial
      epithelial and stromal cells. By immunohistochemistry, Ang(1-7) was localized in
      the endometrium throughout menstrual cycle, being more concentrated in the
      glandular epithelium of mid- and late secretory phase. This pattern corresponded
      to the ACE2 mRNA, which was more abundant in epithelial cells than in stromal
      cells (2-fold increase, p < 0.05) and in the secretory vs. proliferative phase
      (6.6-fold increase, p < 0.01). The receptor Mas was equally distributed between
      epithelial and stromal cells and did not change during menstrual cycle. The
      physiological role of this peptide system in normal and pathological endometrium
      warrants further investigation.

PMID- 19164481
TI  - Heart rate variability analysis allows early asphyxia detection in ovine fetus.
AB  - Fetal heart rate (FHR) monitoring is commonly used to predict asphyxia but
      clinical and experimental studies have questioned its diagnostic value. We
      examined the usefulness of fetal heart rate variability (fHRV) measures in
      detecting early asphyxia using chronically instrumented fetal sheep under
      normoxic (n = 6) and asphyxic conditions (3 umbilical cord occlusions, n = 6).
      The occlusions consistently led to pH decreases from 7.35 +/- 0.01 to 7.09 +/-
      0.03 ( P < .05). FHR showed biphasic deceleration during each occlusion,
      associated with increasing arterial blood pressure ( P < .05). RMSSD, an index of
      vagal modulation of fHRV, increased consistently during repeated occlusion
      induced FHR decelerations ( P < .05). Under normoxic conditions, RMSSD did not
      change during FHR decelerations and decreased during FHR accelerations ( P <
      .05). Our results suggest that an increase of RMSSD in association with FHR
      decelerations reflects initial vagal activation during fetal asphyxia. RMSSD may
      accurately identify asphyxic fetuses early. Clinical validation is needed.

PMID- 19164482
TI  - Health research: measuring the social, health and economic benefits.

PMID- 19164483
TI  - Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by
      human equilibrative nucleoside transporter-3.
AB  - Human equilibrative nucleoside transporter-3 (hENT3) was recently reported as a
      pH-dependent, intracellular (lysosomal) transporter capable of transporting anti
      human immunodeficiency virus (HIV) dideoxynucleosides (ddNs). Because most anti
      HIV ddNs (e.g., zidovudine, AZT) exhibit clinical mitochondrial toxicity, we
      investigated whether hENT3 facilitates transport of anti-HIV ddNs into the
      mitochondria. Cellular fractionation and immunofluorescence microscopy studies in
      several human cell lines identified a substantial presence of hENT3 in the
      mitochondria, with additional presence at the cell surface of two placental cell
      lines (JAR, JEG3). Mitochondrial or cell surface hENT3 expression was confirmed
      in human hepatocytes and placental tissues, respectively. Unlike endogenous
      hENT3, yellow fluorescent protein (YFP)-tagged hENT3 was partially directed to
      the lysosomes. Xenopus oocytes expressing NH2-terminal-deleted hENT3 (expressed
      at the cell surface) showed pH-dependent interaction with several classes of
      nucleosides (anti-HIV ddNs, gemcitabine, fialuridine, ribavirin) that produce
      mitochondrial toxicity. Transport studies in hENT3 gene-silenced JAR cells showed
      significant reduction in mitochondrial transport of nucleosides and nucleoside
      drugs. Our data suggest that cellular localization of hENT3 is cell type
      dependent and the native transporter is substantially expressed in mitochondria
      and/or cell surface. hENT3-mediated mitochondrial transport may play an important
      role in mediating clinically observed mitochondrial toxicity of nucleoside drugs.
      In addition, our finding that hENT3 is a mitochondrial transporter is consistent
      with the recent finding that mutations in the hENT3 gene cause an autosomal
      recessive disorder in humans called the H syndrome.

PMID- 19164484
TI  - Reduced NHE3-mediated Na+ absorption increases survival and decreases the
      incidence of intestinal obstructions in cystic fibrosis mice.
AB  - In cystic fibrosis, impaired secretion resulting from loss of activity of the
      cystic fibrosis transmembrane conductance regulator (CFTR) causes dehydration of
      intestinal contents and life-threatening obstructions. Conversely, impaired
      absorption resulting from loss of the NHE3 Na+/H+ exchanger causes increased
      fluidity of the intestinal contents and diarrhea. To test the hypothesis that
      reduced NHE3-mediated absorption could increase survival and prevent some of the
      intestinal pathologies of cystic fibrosis, Cftr/Nhe3 double heterozygous mice
      were mated and their offspring analyzed. Cftr-null mice lacking one or both
      copies of the NHE3 gene exhibited increased fluidity of their intestinal
      contents, which prevented the formation of obstructions and increased survival.
      Goblet cell hyperplasia was eliminated, but not the accumulation of Paneth cell
      granules or increased cell proliferation in the crypts. Microarray analysis of
      small intestine RNA from Cftr-null, NHE3-null, and double-null mice all revealed
      downregulation of genes involved in xenobiotic metabolism, including a cohort of
      genes involved in glutathione metabolism. Expression of energy metabolism genes
      was altered, but there were no changes in genes involved in inflammation. Total
      intracellular glutathione was increased in the jejunum of all of the mutants and
      the ratio of reduced to oxidized glutathione was reduced in Cftr-null mutants,
      indicating that CFTR deficiency affects intestinal glutathione metabolism. The
      data establish a major role for NHE3 in regulating the fluidity of the intestinal
      contents and show that reduced NHE3-mediated absorption reverses some of the
      intestinal pathologies of cystic fibrosis, thus suggesting that it may serve as a
      potential therapeutic target.

PMID- 19164485
TI  - Spermidine/spermine-N1-acetyltransferase ablation protects against liver and
      kidney ischemia-reperfusion injury in mice.
AB  - Expression of spermine/spermidine-N1-acetyltransferase (SSAT), the rate-limiting
      enzyme of polyamine backconversion cascade, increases after ischemia-reperfusion
      injuries (IRI). We hypothesized that SSAT plays an important role in the
      mediation of IRI. To test our hypothesis, wild-type (SSAT-wt) and SSAT-deficient
      (SSAT-ko) mice were subjected to liver or kidney IRI by ligation of hepatic or
      renal arteries. The liver and kidney content of putrescine (Put), a downstream by
      product of SSAT activity, increased in SSAT-wt animals but not in SSAT-ko animals
      after IRI, indicating that polyamine backconversion is not functional in SSAT
      deficient mice. When subjected to hepatic IRI, SSAT-ko mice were significantly
      protected against liver damage compared with SSAT-wt mice. Similarly, SSAT-ko
      animals subjected to renal IRI showed significantly greater protection against
      damage to kidney tubules than SSAT-wt mice. These studies indicate that SSAT
      deficient animals are protected against IRI and suggest that SSAT is an important
      mediator of the tissue damage in IRI.

PMID- 19164486
TI  - UDP-glucose modulates gastric function through P2Y14 receptor-dependent and 
      independent mechanisms.
AB  - P2Y receptors have been reported to modulate gastrointestinal functions. The
      newest family member is the nucleotide-sugar receptor P2Y14. P2ry14 mRNA was
      detected throughout the rat gut, with the highest level being in the forestomach.
      We investigated the role of the receptor in stomach motility using cognate
      agonists and knockout (KO) mice. In rat isolated forestomach, 100 microM UDP
      glucose and 100 muM UDP-galactose both increased the baseline muscle tension
      (BMT) by 6.2+/-0.6 and 1.6+/-0.6 mN (P<0.05, n=3-4), respectively, and the
      amplitude of contractions during electrical field stimulation (EFS) by 3.7+/-1.7
      and 4.3+/-2.5 mN (P<0.05, n=3-4), respectively. In forestomach from wild-type
      (WT) mice, 100 microM UDP-glucose increased the BMT by 1.0+/-0.1 mN (P<0.05, n=6)
      but this effect was lost in the KO mice (change of -0.1+/-0.1 mN, n=6). The 100
      microM UDP-glucose also increased the contraction amplitude during EFS in this
      tissue from the WT animals (0.9+/-0.4 mN, P < 0.05, n=6) but not from the KO mice
      (0.0+/-0.2 mN, n=6). In vivo, UDP-glucose at 2,000 mg/kg ip reduced gastric
      emptying in rats by 49.7% (P<0.05, n=4-6) and in WT and KO mice by 56.1 and
      66.2%, respectively (P<0.05, n=7-10) vs. saline-treated control animals. There
      was no significant difference in gastric emptying between WT and KO animals
      receiving either saline or d-glucose. These results demonstrate a novel function
      of the P2Y14 receptor associated with contractility in the rodent stomach that
      does not lead to altered gastric emptying after receptor deletion and an ability
      of UDP-glucose to delay gastric emptying without involving the P2Y14 receptor.

PMID- 19164487
TI  - Chemical characterization of oligosaccharides in chimpanzee, bonobo, gorilla,
      orangutan, and siamang milk or colostrum.
AB  - Neutral and acidic oligosaccharides were isolated from the milk or colostrum of
      four great ape species (chimpanzee (Pan troglodytes), bonobo (Pan paniscus),
      gorilla (Gorilla gorilla), and orangutan (Pongo pygmaeus)) and one lesser ape
      species (siamang (Symphalangus syndactylus)), and their chemical structures were
      characterized by (1)H-NMR spectroscopy. Oligosaccharides containing the type II
      unit (Gal(beta1-4)GlcNAc) were found exclusively (gorilla and siamang) or
      predominately (chimpanzee, bonobo, and orangutan) over those containing the type
      I unit (Gal(beta1-3)GlcNAc). In comparison, type I oligosaccharides predominate
      over type II oligosaccharides in human milk, whereas nonprimate milk almost
      always contains only type II oligosaccharides. The milk or colostrum of the great
      apes contained oligosaccharides bearing both N-glycolylneuraminic acid and N
      acetylneuraminic acid, whereas human milk contains only the latter. Great ape
      milk, like that of humans, contained fucosylated oligosaccharides whereas siamang
      milk did not. Since these analyses are based on a limited number of individuals,
      further research on additional samples of great and lesser ape milk is needed to
      confirm phylogenetic patterns.

PMID- 19164488
TI  - Fetoplacental growth and vascular development in overnourished adolescent sheep
      at day 50, 90 and 130 of gestation.
AB  - To establish the basis for altered placental development and function previously
      observed at late gestation, fetoplacental growth and placental vascular
      development were measured at three stages of gestation in a nutritional paradigm
      of compromised pregnancy. Singleton pregnancies to a single sire were established
      and thereafter adolescent ewes were offered an optimal control (C) or a high (H)
      dietary intake. At day 50, the H group had elevated maternal insulin and amniotic
      glucose, whereas mass of the fetus and placenta were unaltered. At day 90, the H
      group exhibited elevated maternal insulin, IGF1 and glucose; fetal weight and
      glucose concentrations in H were increased relative to C, but placental weight
      was independent of nutrition. By day 130, total placentome weight in the H group
      was reduced by 46% and was associated with lower fetal glucose and a 20%
      reduction in fetal weight. As pregnancy progressed from day 50 to 130, the
      parameters of vascular development in the maternal and fetal components of the
      placenta increased. In the fetal cotyledon, high dietary intakes were associated
      with impaired vascular development at day 50 and an increase in capillary number
      at day 90. At day 130, all vascular indices were independent of nutrition. Thus,
      high dietary intakes to promote rapid maternal growth influence capillary
      development in the fetal portion of the placenta during early to mid-pregnancy
      and may underlie the subsequent reduction in placental mass and hence fetal
      nutrient supply observed during the final third of gestation.

PMID- 19164489
TI  - Aberration-corrected ADF-STEM depth sectioning and prospects for reliable 3D
      imaging in S/TEM.
AB  - The short depth of focus of aberration-corrected scanning transmission electron
      microscopes (STEMs) could potentially enable 3D reconstruction of nanomaterials
      through acquisition of a through-focal series. However, the contrast transfer
      function of annular dark-field (ADF)-STEM depth sectioning has a missing-cone
      problem similar to that of tilt-series tomography. The elongation as a function
      of the probe-forming angle is found to be (square root of 3/2) x 1/alphamax. For
      existing aberration-corrected STEMs operated at optimal imaging conditions, the
      elongation factor for depth sectioning is larger than 30. This large elongation
      factor results in highly distorted shapes of 3D objects and unexpected artifacts
      due to the loss of information. Depth-sectioning experiments using a 33-mrad 100
      keV C(5)-corrected aberration-corrected STEM demonstrate the elongation effect
      and the missing-cone problem in real and reciprocal space. The performance limits
      of different S/TEM-based imaging modes are compared. There is a missing cone of
      information for bright-field S/TEM, ADF-STEM, hollow-cone ADF-STEM and coherent
      scanning confocal electron microscopy (SCEM). Only incoherent SCEM fills the
      missing cone.

PMID- 19164490
TI  - Quetiapine versus clomipramine in the augmentation of selective serotonin
      reuptake inhibitors for the treatment of obsessive-compulsive disorder: a
      randomized, open-label trial.
AB  - After 12 weeks of selective serotonin reuptake inhibitor (SSRI) monotherapy with
      inadequate response, 10 patients received clomipramine and 11 received quetiapine
      as augmentation agents of the SSRI. The primary outcome measure was the
      difference between initial and final scores of the Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS), rated in a blinded fashion, and the score of clinical
      global improvement (CGI-I). Statistical analyses were performed using
      nonparametric tests to evaluate treatment efficacy and the difference between
      treatment groups. Percentile plots were constructed with YBOCS scores from the
      clomipramine and quetiapine groups. Considering response a >or=35% reduction in
      the initial Y-BOCS score plus a rating of 'much improved' or 'very much improved'
      on CGI-I, four of eleven quetiapine patients and one out of ten clomipramine
      patients were classified as responders. The mean final Y-BOCS score was
      significantly lower than baseline in the quetiapine augmentation group (P =
      0.023), but not in the clomipramine augmentation group (P = 0.503). The
      difference between groups showed a trend towards significance only at week 4, the
      mean Y-BOCS score being lower for those receiving quetiapine (P = 0.052). A
      difference between groups was also observed at week 4 according to percentile
      plots. These results corroborate previous findings of quetiapine augmentation
      efficacy in obsessive-compulsive disorder (OCD). Clomipramine augmentation did
      not produce a significant reduction in Y-BOCS scores. Higher target maximum
      dosages might have yielded different results.

PMID- 19164491
TI  - N-methyl-D-aspartate receptors are involved in lithium-induced state-dependent
      learning in mice.
AB  - We have previously shown lithium-induced state-dependent learning in a step-down
      inhibitory avoidance task. In the present study, the effects of
      intracerebroventricular injections of N-methyl-D-aspartate (NMDA) receptor agents
      on the lithium-induced state-dependent learning have been investigated. A single
      trial step-down inhibitory avoidance task was used to assess memory in male Naval
      Medical Research Institute (NMRI) mice. The results showed that post-training
      lithium (10 mg/kg) decreased the step-down latency on the test day, which was
      reversed by pre-test administration of the same dose of the drug; indicating
      state-dependent learning induced by lithium. Pre-test administration of NMDA
      (0.0001, 0.001 and 0.01 microg/mouse, intracerebroventricular) could also
      substitute for pre-test lithium to reverse the decrease of the step-down latency
      induced by post-training lithium. Furthermore, pre-test co-administration of an
      ineffective dose of NMDA (0.00001 microg/mouse, intracerebroventricular.) with
      lower doses of lithium (1.25, 2.5 and 5 mg/kg, intraperitoneally.)
      synergistically reversed the decrease of the step-down latency. On the contrary,
      pre-test injections of NMDA receptor antagonist D-AP5 (0.25, 0.5, 1 and 2
      microg/mouse, intracerebroventricular.) disrupted state-dependent learning
      induced by lithium. The results suggest that NMDA receptors may be involved, at
      least partly, in the lithium-induced state-dependent learning.

PMID- 19164492
TI  - Double-blind, placebo-controlled evaluation of extended-release bupropion in
      elderly patients with major depressive disorder.
AB  - Major depressive disorder in the elderly is associated with increased morbidity
      and reduced quality of life. This 10 week, placebo-controlled study investigated
      the efficacy and tolerability of extended-release bupropion (150-300 mg once
      daily) in depressed patients aged 65 years or older. The statistical assumptions
      necessary for the validity of the protocol-specified analysis of covariance were
      not met for the analysis of the primary outcome variable (Montgomery-Asberg
      Depression Rating Scale total score at Week 10, last observation carried
      forward). Alternative statistical methods used for the analysis of this variable
      demonstrated statistical significance. Statistically significant improvements
      were observed on the majority of secondary end points when compared with placebo,
      including the health outcome measures for motivation and energy, and life
      satisfaction and contentment. Adverse events were generally mild to moderate and
      similar between treatment groups. This study demonstrated that the extended
      release bupropion is an effective, well-tolerated treatment for major depression
      in the elderly.

PMID- 19164493
TI  - The uses and outcomes of quetiapine in depressive and bipolar mood disorders in
      clinical practice.
AB  - We conducted an electronic chart review of a sample of all people attending
      secondary mental health care, in the county of Lanarkshire, Scotland, who were
      commenced on quetiapine for the following mood disorders: non-psychotic
      depression (n = 171), psychotic depression (n = 39), bipolar mania (n = 24),
      bipolar depression (n = 38) and bipolar mixed states (n = 31), between 2002 and
      2007. We retrospectively assigned severity and improvement Clinical Global
      Impression (CGI) scores to measure effectiveness. Quetiapine was co-prescribed
      with antidepressants in 75-97% of depressive disorders. Commencing quetiapine was
      associated with clinical improvement in >64% of all patients, median doses (200
      400 mg/day). For all depressive subtypes (non-psychotic, psychotic and bipolar)
      quetiapine was associated with improvement in 69% of patients. Across CGI
      measures, bipolar mania patients had the best outcome (89% improved). In bipolar
      mania, higher maximum doses were associated with greater improvement and 45% were
      continued on antidepressants. The results should be interpreted with caution due
      to the observational nature of the study and findings may not be attributed to
      the effects of quetiapine alone. Quetiapine was used mainly as an adjunct to
      other antidepressant and mood stabilising agents. The pharmacological profile of
      quetiapine suggests its properties extend beyond antipsychotic action, to
      antidepressant, anxiolytic and mood stabilising effects.

PMID- 19164494
TI  - Cognitive effects of antipsychotic dosage and polypharmacy: a study with the BACS
      in patients with schizophrenia and schizoaffective disorder.
AB  - Antipsychotic polypharmacy and high doses have been associated with poorer
      outcome, longer hospital stays, and increased side effects. The present
      naturalistic study assessed the cognitive effects of antipsychotics in 56
      patients with a diagnosis of schizophrenia or schizoaffective disorder, using the
      Brief Assessment of Cognition in Schizophrenia (BACS). Antipsychotic daily dose
      (ADD) was expressed as mg risperidone equivalents/day (RIS eq), using a model
      based on drug doses from the Clinical Antipsychotic Trials in Intervention
      Effectiveness (CATIE) study for second generation antipsychotics (SGA) and
      chlorpromazine equivalents for first generation antipsychotics (FGA), with a 1/1
      equivalence between haloperidol and risperidone. Increasing age was associated
      with polypharmacy, FGA prescription and decreasing BACS score. FGA prescription,
      in turn, predicted a poorer cognitive functioning, independently of age, PANSS
      subscores and ADD. ADD was associated with decreasing cognitive scores, an effect
      that remained significant after controlling for age, PANSS or polypharmacy. The
      detrimental cognitive effects of polypharmacy, in turn, appeared to be mediated
      by ADD. Different methods of data fitting suggested that ADD above 5-6 mg RIS
      eq/day were associated with lower BACS scores. Overall, these results show that
      increasing antipsychotic daily dose is associated with poorer cognitive
      functioning at doses lower than previously thought, independently of the number
      of antipsychotic drugs.

PMID- 19164495
TI  - The role of flumazenil in the treatment of benzodiazepine dependence:
      physiological and psychological profiles.
AB  - Two-related studies are presented here, detailing our early experience with
      benzodiazepine-dependent patients treated with a four-day flumazenil infusion
      using a novel delivery technique. Patients with long-term benzodiazepine
      dependence who attended the Australian Medical Procedures Research Foundation
      (AMPRF, Perth, Australia) for treatment were recruited for these studies. Self
      reported psychological and physical symptoms, as well as objective vital signs
      data were collected at intervals before, during and 2 weeks postinfusion. Study A
      is a case series with cardiovascular measures; study B is an open trial that
      tracks the psychological profiles of 13 subjects. Withdrawal symptoms were
      tracked, however, the nature and severity of these symptoms differed between
      patients. No major complications or discomfort prompting study dropout was
      observed. Significant benzodiazepine abstinence occurred with this flumazenil
      infusion method despite high levels of initial dependence, comorbid substance use
      and comorbid psychiatric illness. Low-dose flumazenil infusion appears to be a
      safe and effective treatment resulting in withdrawal symptoms of lesser severity
      than any other cessation method currently available. Recommendations for future
      research are discussed.

PMID- 19164496
TI  - Effect of lactational exposure of olanzapine on body weight of mice: a
      comparative study on neonates of both the sexes during post-natal development.
AB  - Adverse impact of atypical antipsychotic drugs on body weight of adult and
      juvenile groups has been well-documented both at clinical and preclinical
      investigations. However, studies on impact of drug on body weight during fetal or
      neonatal development received little attention. The present study is the first
      ever preclinical investigation demonstrating the effect of lactational exposure
      of olanzapine (4, 8, and 10 mg/kg) and risperidone (1 and 2 mg/kg), two widely
      prescribed antipsychotics, on body weight of mice neonates. Body weight gain was
      observed with both the drugs, although a sex-related differential response was
      noted. In olanzapine-exposed female neonates, the weight gain was more with the
      highest dose. Male neonates showed a reverse trend, i.e. the highest gain with
      the lowest dose. Female neonates exposed to risperidone also showed significant,
      but less gain as compared to their olanzapine-exposed counterparts. Risperidone
      exposed male neonates showed little body weight gain. Waist-to-hip ratio and
      plasma prolactin level were measured to explain the reason behind the body weight
      gain, but there were deviations with respect to drug and sex. The body weight
      gain may be the overall manifestations of drug-induced endocrine and metabolic
      dysregulations.

PMID- 19164497
TI  - Mood state moderates the role of serotonin in cognitive biases.
AB  - Reduction of the monoamine serotonin (5-HT) via the dietary manipulation of
      tryptophan (acute tryptophan depletion; ATD) has been shown to induce negative
      cognitive biases similar to those found in depression in healthy individuals.
      However, evidence also indicates that there can be positive effects of ATD on
      both mood and reinforcement processing. Here, we present two separate studies,
      with remarkably similar findings, which may help explain these discrepancies. In
      both experiments, we assessed cognitive biases following experimentally induced
      mood states under both a balanced amino acid drink (BAL) and ATD. A significant
      interaction between treatment, mood state and cognitive bias was observed in both
      experiments. In the first experiment, subjects undergoing positive mood induction
      demonstrated a positive cognitive bias on BAL, which was abolished by ATD. The
      same effect was observed in subjects undergoing neutral mood induction in the
      second experiment. These effects replicate findings in healthy individuals
      undergoing ATD. Subjects undergoing negative mood induction, by contrast,
      demonstrated the opposite pattern of results; in both experiments, they showed no
      bias under BAL but induction of a positive cognitive bias by ATD. These results
      mimic previous findings in currently depressed patients undergoing ATD. We
      therefore suggest that mood state moderates the effect of ATD on cognitive
      biases. This, in turn, has important implications for the understanding of the
      role of 5-HT in psychiatric disorders.

PMID- 19164498
TI  - Acute psychomotor effects of MDMA and ethanol (co-) administration over time in
      healthy volunteers.
AB  - In Western societies, a considerable percentage of young people use 3,4
      methylenedioxymethamphetamine (MDMA or 'ecstasy'). The use of alcohol (ethanol)
      in combination with ecstasy is common. The aim of the present study was to assess
      the acute psychomotor and subjective effects of (co-) administration of MDMA and
      ethanol over time and in relation to the pharmacokinetics. We performed a four
      way, double blind, randomized, crossover, placebo-controlled study in 16 healthy
      volunteers (nine men, seven women) between the ages of 18 and 29. MDMA (100 mg)
      was given orally while blood alcohol concentration was maintained at pseudo
      steady state levels of approximately 0.6 per thousand for 3 h by a 10%
      intravenous ethanol clamp. MDMA significantly increased psychomotor speed but did
      not affect psychomotor accuracy and induced subjective arousal. Ethanol impaired
      both psychomotor speed and accuracy and induced sedation. Coadministration of
      ethanol and MDMA improved psychomotor speed but impaired psychomotor accuracy
      compared with placebo and reversed ethanol-induced sedation. Pharmacokinetics and
      pharmacodynamics showed maximal effects at 90-150 min after MDMA administration
      after which drug effects declined in spite of persisting MDMA plasma
      concentration, with the exception of ethanol-induced sedation, which manifested
      itself fully only after the infusion was stopped. In conclusion, results show
      that subjects were more aroused when intoxicated with both substances combined
      compared with placebo, but psychomotor accuracy was significantly impaired. These
      findings may have implications for general neuropsychological functioning as this
      may provide a sense of adequate performance that does not agree with a
      significant reduction in psychomotor accuracy.

PMID- 19164500
TI  - Ziprasidone-induced spontaneous orgasm.
AB  - Neuroleptic treatment in schizophrenic patients has been associated with sexual
      dysfunction, including impotence and decreased libido. Spontaneous ejaculation
      without sexual arousal during typical antipsychotic treatment is a rare condition
      that has been described with zuclopentixol, trifluoperazine, and thiothixene.
      Here, we are reporting a case of spontaneous orgasm with ziprasidone in a bipolar
      patient. This patient began to repeatedly experience spontaneous sexual arousal
      and orgasm, which she had never experienced in the past. Ziprasidone might be
      causing an increase in sexual orgasm by 5-HT2 receptor antagonism, which
      preclinical evidence suggests that it facilitates dopamine release in the cortex.

PMID- 19164499
TI  - Psychiatrists' attitude towards and knowledge of clozapine treatment.
AB  - Clozapine is, in most countries, underutilized and the initiation of clozapine is
      often delayed. The purpose of this study is to investigate the reasons for the
      delay and the underutilization of clozapine. One hundred psychiatrists were
      interviewed by phone. The interview was a structured interview with questions
      regarding attitude to, knowledge of and experiences with clozapine. Forty-eight
      (48%) psychiatrists had treatment responsibility of fewer than five patients
      treated with clozapine and 31 of the interviewed psychiatrists (31%) had started
      clozapine within the last 3 months. Seven psychiatrists (7%) had never prescribed
      clozapine despite the fact that they had been working more than five years in
      general psychiatry. Sixty-four psychiatrists (64%) would rather combine two
      antipsychotics than use clozapine. Sixty-six psychiatrists (66%) believed that
      patients treated with clozapine were less satisfied with their treatment when
      compared with those treated with other atypical antipsychotics. Many
      psychiatrists are reluctant to use clozapine and this might be due to less
      experience and knowledge of clozapine. A reason for the low awareness of
      clozapine's properties might be that clozapine is now a generic drug, and
      therefore, the marketing and education in using the drug is sparse.

PMID- 19164501
TI  - Morphine-induced stereotyped thigmotaxis could appear as enhanced fear and
      anxiety in some behavioural tests.
AB  - This study questions whether the classical interpretation for unconditional
      fear/anxiety tests is valid when animals are under the influence of some drugs of
      abuse. We used a modified version of the trimethylthiazoline (TMT)-avoidance
      task, a measure of unconditional fear. Halfway into a corridor maze we placed a 3
      cm-high barrier. This provided a wall in the middle of the corridor, one that the
      mice can easily climb over. Saline- and morphine-treated mice were randomly
      placed in the 'safe' or 'unsafe' (TMT) side and observed for 10 min. As expected,
      saline-injected mice spent only about 25% of the time in the TMT side, regardless
      of the side they were initially placed into. In contrast, morphine-treated mice
      did not cross the barrier even once, regardless of their initial placement.
      Specifically, morphine-treated mice initially placed in the TMT side appeared to
      exhibit the expected reduction in unconditional fear, that is, spending the
      entire time in the TMT side, a significant increase over the controls. Yet,
      morphine-treated mice placed in the safe side never even entered the TMT side;
      thus, these mice appeared to exhibit a behavioural response that is classically
      interpreted as increased fear, that is, spending significantly less time in the
      TMT side versus the controls. In summary, this study demonstrates that the
      classical interpretation of some unconditioned fear or anxiety tests could be
      misleading when animals are under the influence of drugs that might induce other
      competing behaviours.

PMID- 19164503
TI  - CLPs find their inner T-cell potential.

PMID- 19164502
TI  - B-CLL kicks it up a Notch.

PMID- 19164504
TI  - Fractalkine: one chemokine, many functions.

PMID- 19164505
TI  - Pneumonic plague pathogenesis and immunity in Brown Norway rats.
AB  - The Brown Norway rat was recently described as a bubonic plague model that
      closely mimics human disease. We therefore evaluated the Brown Norway rat as an
      alternative small animal model for pneumonic plague and characterized both the
      efficacy and potency of vaccine candidates. When infected by intranasal
      instillation, these rats rapidly developed fatal pneumonic plague within 2 to 4
      days of infection. Plague disease was characterized by severe alveolar edema and
      vascular hemorrhage in the lung in addition to fulminant necrotizing pneumonia
      caused by massive bacterial replication and inflammation. Twenty-four hours
      before death, animals developed systemic disease with an apparent delayed
      inflammatory response. We evaluated the ability of the protective antigen, LcrV,
      and a mutant derivative, V10, to protect these rats from pneumonic plague. Both
      were highly effective vaccines because complete protection was observed at
      challenge doses of 7500 LD(50). Antibody analyses suggested stronger potency of
      V10 immune sera compared with LcrV in the passive transfer of immunity to bubonic
      plague, with multiple neutralizing epitopes in LcrV. Taken together, these data
      demonstrate the effectiveness of inhibiting type III secretion in the prevention
      of pneumonic plague in rats and reveal critical contributions from both the
      cellular and humoral immune systems. Thus, the Brown Norway rat is an appealing
      alternative small animal model for the study of pneumonic plague pathogenesis and
      immunity.

PMID- 19164506
TI  - The neuronal expression of MYC causes a neurodegenerative phenotype in a novel
      transgenic mouse.
AB  - Many different proteins associated with the cell cycle, including cyclins, cyclin
      dependent kinases, and proto-oncogenes such as c-MYC (MYC), are increased in
      degenerating neurons. Consequently, an ectopic activation of the cell cycle
      machinery in neurons has emerged as a potential pathogenic mechanism of neuronal
      dysfunction and death in many neurodegenerative diseases, including Alzheimer's
      disease. However, the exact role of cell cycle re-entry during disease
      pathogenesis is unclear, primarily because of the lack of relevant research
      models to study the effects of cell cycle re-entry on mature neurons in vivo. To
      address this issue, we developed a new transgenic mouse model in which forebrain
      neurons (CaMKII-MYC) can be induced to enter the cell cycle using the
      physiologically relevant proto-oncogene MYC to drive cell cycle re-entry. We show
      that such cell cycle re-entry results in neuronal cell death, gliosis, and
      cognitive deficits. These findings provide compelling evidence that dysregulation
      of cell cycle re-entry results in neurodegeneration in vivo. Our current
      findings, coupled with those of previous reports, strengthen the hypothesis that
      neurodegeneration in Alzheimer's disease, similar to cellular proliferation in
      cancer, is a disease that results from inappropriate cell cycle control.

PMID- 19164507
TI  - The E693Delta mutation in amyloid precursor protein increases intracellular
      accumulation of amyloid beta oligomers and causes endoplasmic reticulum stress
      induced apoptosis in cultured cells.
AB  - The E693Delta mutation within the amyloid precursor protein (APP) has been
      suggested to cause dementia via the enhanced formation of synaptotoxic amyloid
      beta (Abeta) oligomers. However, this mutation markedly decreases Abeta
      secretion, implying the existence of an additional mechanism of neuronal
      dysfunction that is independent of extracellular Abeta. We therefore examined the
      effects of this mutation on both APP processing to produce Abeta as well as
      subcellular localization and accumulation of Abeta in transfected HEK293 and COS
      7 cells. Both beta- and gamma-cleavage of mutant APP increased, indicating a lack
      of inhibition in Abeta production. Instead, this mutation promoted Abeta
      accumulation within cells, including the endoplasmic reticulum (ER), Golgi
      apparatus, early and late endosomes, lysosomes, and autophagosomes, all of which
      have been proposed as intracellular sites of Abeta generation and/or degradation,
      suggesting impairment of APP/Abeta trafficking. Notably, the intracellular mutant
      Abeta was found to predominantly form oligomers. Concomitant with this
      accumulation, the ER stress markers Grp78 and phosphorylated eIF2alpha were both
      strongly induced. Furthermore, the activation of caspase-4 and -3 as well as DNA
      fragmentation were detected in these cells. These results suggest that mutant
      Abeta induces alteration of Abeta trafficking and subsequent ER stress-induced
      apoptosis via enhancement of its intracellular oligomerization. Our findings
      suggest that Abeta oligomers exhibit toxicity in the extracellular space and
      within the cells themselves.

PMID- 19164508
TI  - Podocyte repopulation contributes to regression of glomerular injury induced by
      ACE inhibition.
AB  - Angiotensin-converting enzyme (ACE) inhibition induces glomerular repair in the
      Munich Wistar Fromter (MWF) rat, a model of spontaneous glomerular injury. In
      this study, we investigated whether this effect is related to changes in
      glomerular cell number, particularly of podocytes, which are progressively lost
      with age. MWF rats with advanced nephropathy were studied at both 40 weeks and
      after 20 weeks of observation either with or without treatment with the ACE
      inhibitor lisinopril. Forty-week-old Wistar rats were used as controls. In
      untreated MWF rats, proteinuria, hypertension, glomerulosclerosis, and renal
      function worsened, while lisinopril induced regression of both functional and
      structural changes. Despite glomerular hypercellularity in untreated MWF rats,
      the number of endothelial cells per glomerulus did not change, and podocyte
      number even decreased. ACE inhibition halted the progressive increase in
      glomerular cell number and enhanced endothelial cell volume density.
      Surprisingly, lisinopril not only halted age-related podocyte loss but also
      increased the number of glomerular podocytes above baseline, which was associated
      with an increased number of proliferating Wilms tumor 1-positive cells, loss of
      cyclin-dependent kinase inhibitor p27 expression, and increased number of
      parietal podocytes. These data indicate that ACE inhibition restructures
      glomerular capillary, primarily by restoring the podocyte population in this
      model of glomerular injury. Increased parietal podocyte number in lisinopril
      treated MWF rats suggests that the remodeling of Bowman's capsule epithelial
      cells contributes to this effect.

PMID- 19164509
TI  - Suppressive effect of orthovanadate on hepatic stellate cell activation and liver
      fibrosis in rats.
AB  - Orthovanadate (OV), an inhibitor of protein tyrosine phosphatases, affects
      various biological processes in a cell-type-specific manner. In this study, we
      investigated the effect of OV on hepatic stellate cells (HSCs). When primary rat
      HSCs were cultured in the presence of 10% serum, they spontaneously lost
      characteristic stellate morphology, proliferated, and were transformed into an
      activated state with the formation of abundant stress fibers and increased
      expression of both alpha-smooth muscle actin and collagen type I mRNA. OV
      treatment inhibited proliferation and activation of HSCs and partially reversed
      the phenotype of activated HSCs. Among the signaling molecules investigated,
      phosphorylation of the Src protein at tyrosine 416 was the most striking in OV
      treated HSCs. Treatment of cells with Src family inhibitors partially abrogated
      the effects of OV. Furthermore, transfection of v-Src into activated HSCs induced
      a stellate morphology similar to that in the quiescent state. We then examined
      whether OV could effectively suppress HSC activation in vivo after liver injury
      induced by either carbon tetrachloride or dimethylnitrosamine. OV significantly
      reduced the appearance of alpha-smooth muscle actin-positive cells and decreased
      collagen deposition, concomitant with an improvement in liver function. Our study
      showed for the first time that OV was able to suppress the activation of HSCs,
      possibly through the modulation of Src activity, and attenuated fibrosis after
      chronic liver injury.

PMID- 19164510
TI  - Anthropogenic enhancement of Egypt's Mediterranean fishery.
AB  - The highly productive coastal Mediterranean fishery off the Nile River delta
      collapsed after the completion of the Aswan High Dam in 1965. But the fishery has
      been recovering dramatically since the mid-1980s, coincident with large increases
      in fertilizer application and sewage discharge in Egypt. We use stable isotopes
      of nitrogen (delta(15)N) to demonstrate that 60%-100% of the current fishery
      production may be from primary production stimulated by nutrients from fertilizer
      and sewage runoff. Although the establishment of the dam put Egypt in an ideal
      position to observe the impact of rapid increases in nutrient loading on coastal
      productivity in an extremely oligotrophic sea, the Egyptian situation is not
      unique. Such anthropogenically enhanced fisheries also may occur along the
      northern rim of the Mediterranean and offshore of some rapidly developing
      tropical countries, where nutrient concentrations in the coastal waters were
      previously very low.

PMID- 19164511
TI  - Nicotine activates TRPM5-dependent and independent taste pathways.
AB  - The orosensory responses elicited by nicotine are relevant for the development
      and maintenance of addiction to tobacco products. However, although nicotine is
      described as bitter tasting, the molecular and neural substrates encoding the
      taste of nicotine are unclear. Here, rats and mice were used to determine whether
      nicotine activates peripheral and central taste pathways via TRPM5-dependent
      mechanisms, which are essential for responses to other bitter tastants such as
      quinine, and/or via nicotinic acetylcholine receptors (nAChRs). When compared
      with wild-type mice, Trpm5(-/-) mice had reduced, but not abolished, chorda
      tympani (CT) responses to nicotine. In both genotypes, lingual application of
      mecamylamine, a nAChR-antagonist, inhibited CT nerve responses to nicotine and
      reduced behavioral responses of aversion to this stimulus. In accordance with
      these findings, rats were shown to discriminate between nicotine and quinine
      presented at intensity-paired concentrations. Moreover, rat gustatory cortex (GC)
      neural ensemble activity could also discriminate between these two bitter
      tastants. Mecamylamine reduced both behavioral and GC neural discrimination
      between nicotine and quinine. In summary, nicotine elicits taste responses
      through peripheral TRPM5-dependent pathways, common to other bitter tastants, and
      nAChR-dependent and TRPM5-independent pathways, thus creating a unique sensory
      representation that contributes to the sensory experience of tobacco products.

PMID- 19164512
TI  - Recurrent genomic alterations characterize medulloblastoma arising from DNA
      double-strand break repair deficiency.
AB  - Inactivation of homologous recombination (HR) or nonhomologous end-joining (NHEJ)
      predisposes to a spectrum of tumor types. Here, we inactivated DNA double-strand
      break repair (DSBR) proteins, DNA Ligase IV (Lig4), Xrcc2, and Brca2, or combined
      Lig4/Xrcc2 during neural development using Nestin-cre. In all cases, inactivation
      of these repair factors, together with p53 loss, led to rapid medulloblastoma
      formation. Genomic analysis of these tumors showed recurring chromosome 13
      alterations via chromosomal loss or translocations involving regions containing
      Ptch1. Sequence analysis of the remaining Ptch1 allele showed a variety of
      inactivating mutations in all tumors analyzed, highlighting the critical tumor
      suppressor function of this hedgehog-signaling regulator. We also observed
      genomic amplification or up-regulation of either N-Myc or cyclin D2 in all
      medulloblastomas. Additionally, chromosome 19, which contains Pten, was also
      selectively deleted in medulloblastoma arising after disruption of HR. Thus, our
      data highlight the preeminence of Ptch1 as a tumor suppressor in cerebellar
      granule cells and reveal other genomic events central to the genesis of
      medulloblastoma.

PMID- 19164513
TI  - Prey choice and habitat use drive sea otter pathogen exposure in a resource
      limited coastal system.
AB  - The processes promoting disease in wild animal populations are highly complex,
      yet identifying these processes is critically important for conservation when
      disease is limiting a population. By combining field studies with epidemiologic
      tools, we evaluated the relationship between key factors impeding southern sea
      otter (Enhydra lutris nereis) population growth: disease and resource limitation.
      This threatened population has struggled to recover despite protection, so we
      followed radio-tagged sea otters and evaluated infection with 2 disease-causing
      protozoal pathogens, Toxoplasma gondii and Sarcocystis neurona, to reveal risks
      that increased the likelihood of pathogen exposure. We identified patterns of
      pathogen infection that are linked to individual animal behavior, prey choice,
      and habitat use. We detected a high-risk spatial cluster of S. neurona infections
      in otters with home ranges in southern Monterey Bay and a coastal segment near
      San Simeon and Cambria where otters had high levels of infection with T. gondii.
      We found that otters feeding on abalone, which is the preferred prey in a
      resource-abundant marine ecosystem, had a very low risk of infection with either
      pathogen, whereas otters consuming small marine snails were more likely to be
      infected with T. gondii. Individual dietary specialization in sea otters is an
      adaptive mechanism for coping with limited food resources along central coastal
      California. High levels of infection with protozoal pathogens may be an adverse
      consequence of dietary specialization in this threatened species, with both
      depleted resources and disease working synergistically to limit recovery.

PMID- 19164514
TI  - Alternatively spliced Spalax heparanase inhibits extracellular matrix
      degradation, tumor growth, and metastasis.
AB  - Heparanase is an endoglycosidase that degrades heparan sulfate (HS) at the cell
      surface and in the extracellular matrix. Heparanase is expressed mainly by cancer
      cells, and its expression is correlated with increased tumor aggressiveness,
      metastasis, and angiogenesis. Here, we report the cloning of a unique splice
      variant (splice 36) of heparanase from the subterranean blind mole rat (Spalax).
      This splice variant results from skipping part of exon 3, exons 4 and 5, and part
      of exon 6 and functions as a dominant negative to the wild-type enzyme. It
      inhibits HS degradation, suppresses glioma tumor growth, and decreases
      experimental B16-BL6 lung colonization in a mouse model. Intriguingly, Spalax
      splice variant 7 of heparanase (which results from skipping of exon 7) is devoid
      of enzymatic activity, but unlike splice 36 it enhances tumor growth. Our results
      demonstrate that alternative splicing of heparanase regulates its enzymatic
      activity and might adapt the heparanase function to the fluctuating normoxic
      hypoxic subterranean environment that Spalax experiences. Development of
      anticancer drugs designed to suppress tumor growth, angiogenesis, and metastasis
      is a major challenge, of which heparanase inhibition is a promising approach. We
      anticipate that the heparanase splicing model, evolved during 40 million years of
      Spalacid adaptation to underground life, would pave the way for the development
      of heparanase-based therapeutic modalities directed against angiogenesis, tumor
      growth, and metastasis.

PMID- 19164515
TI  - HIV-1 Rev protein assembles on viral RNA one molecule at a time.
AB  - Oligomerization of the HIV-1 protein Rev on the Rev Response Element (RRE)
      regulates nuclear export of genomic viral RNA and partially spliced viral mRNAs
      encoding for structural proteins. Single-molecule fluorescence spectroscopy has
      been used to dissect the multistep assembly pathway of this essential
      ribonucleoprotein, revealing dynamic intermediates and the mechanism of assembly.
      Assembly is initiated by binding of Rev to a high-affinity site in stem-loop IIB
      of the RRE and proceeds rapidly by addition of single Rev monomers, facilitated
      by cooperative Rev-Rev interactions on the RRE. Dwell-time analysis of
      fluorescence trajectories recorded during individual Rev-RRE assembly reactions
      has revealed the microscopic rate constants for several of the Rev monomer
      binding and dissociation steps. The high-affinity binding of multiple Rev
      monomers to the RRE is achieved on a much faster timescale than reported in
      previous bulk kinetic studies of Rev-RRE association, indicating that
      oligomerization is an early step in complex assembly.

PMID- 19164516
TI  - A signal-anchor sequence stimulates signal recognition particle binding to
      ribosomes from inside the exit tunnel.
AB  - Sorting of eukaryotic membrane and secretory proteins depends on recognition of
      ribosome-bound nascent chain signal sequences by the signal recognition particle
      (SRP). The current model suggests that the SRP cycle is initiated when a signal
      sequence emerges from the ribosomal tunnel and binds to SRP. Then elongation is
      slowed until the SRP-bound ribosome-nascent chain complex (RNC) is targeted to
      the SRP receptor in the endoplasmic reticulum (ER) membrane. The RNC is then
      transferred to the translocon, SRP is released, and translation resumes. Because
      RNCs do not target to the translocon efficiently if nascent chains become too
      long, the window for SRP to identify its substrates is short. We now show that a
      transmembrane signal-anchor sequence (SA) significantly enhances binding of SRP
      to RNCs even before the SA emerges from the ribosomal tunnel. In this mode, SRP
      does not contact the SA directly but is in close proximity to the portion of the
      nascent polypeptide that has already left the ribosomal tunnel. Early recruitment
      of SRP provides a mechanism to expand the window for substrate identification. We
      suggest that the dynamics of the SRP-ribosome interaction is affected not only by
      the direct binding of SRP to an exposed signal sequence but also by properties of
      the translating ribosome that are triggered from within the tunnel.

PMID- 19164517
TI  - Two amino acid residues determine 2-APB sensitivity of the ion channels TRPV3 and
      TRPV4.
AB  - Temperature-activated transient receptor potential ion channels (thermoTRPs) are
      polymodal detectors of various stimuli including temperature, voltage, and
      chemicals. To date, it is not known how TRP channels integrate the action of such
      disparate stimuli. Identifying specific residues required for channel-activation
      by distinct stimuli is necessary for understanding overall TRP channel function.
      TRPV3 is activated by warm temperatures and various chemicals, and is modulated
      by voltage. One potent activator of TRPV3 is 2-aminoethyl diphenylborinate (2
      APB), a synthetic chemical that modulates many TRP channels. In a high-throughput
      mutagenesis screen of approximately 14,000 mutated mouse TRPV3 clones, we found 2
      residues (H426 and R696) specifically required for sensitivity of TRPV3 to 2-APB,
      but not to camphor or voltage. The cytoplasmic N-terminal mutation H426N in
      human, dog, and frog TRPV3 also effectively abolished 2-APB activation without
      affecting camphor responses. Interestingly, chicken TRPV3 is weakly sensitive to
      2-APB, and the equivalent residue at 426 is an asparagine (N). Mutating this
      residue to histidine induced 2-APB sensitivity of chicken TRPV3 to levels
      comparable for other TRPV3 orthologs. The cytoplasmic C-terminal mutation R696K
      in the TRP box displayed 2-APB specific deficits only in the presence of
      extracellular calcium, suggesting involvement in gating. TRPV4, a related
      thermoTRP, is 2-APB insensitive and has variant sequences at both residues
      identified here. Remarkably, mutating these 2 residues in TRPV4 to TRPV3
      sequences (N426H and W737R) was sufficient to induce TRPV3-like 2-APB
      sensitivity. Therefore, 2-APB activation of TRPV3 is separable from other
      activation mechanisms, and depends on 2 cytoplasmic residues.

PMID- 19164518
TI  - The influence of oceanographic fronts and early-life-history traits on
      connectivity among littoral fish species.
AB  - The spatial distribution of neutral genetic diversity is mainly influenced by
      barriers to dispersal. The nature of such barriers varies according to the
      dispersal means and capabilities of the organisms concerned. Although these
      barriers are often obvious on land, in the ocean they can be more difficult to
      identify. Determining the relative influence of physical and biotic factors on
      genetic connectivity remains a major challenge for marine ecologists. Here, we
      compare gene flow patterns of 7 littoral fish species from 6 families with a
      range of early-life-history traits sampled at the same geographic locations
      across common environmental discontinuities in the form of oceanic fronts in the
      Western Mediterranean. We show that these fronts represent major barriers to gene
      flow and have a strong influence on the population genetic structure of some fish
      species. We also found no significant relation between the early-life-history
      traits most commonly investigated (egg type, pelagic larval duration, and inshore
      offshore spawning) and gene flow patterns, suggesting that other life-history
      factors should deserve attention. The fronts analyzed and the underlying physical
      mechanisms are not site-specific but common among the oceans, suggesting the
      generality of our findings.

PMID- 19164519
TI  - A critical role for IL-21 receptor signaling in the pathogenesis of systemic
      lupus erythematosus in BXSB-Yaa mice.
AB  - Interleukin 21 (IL-21) is a pleiotropic cytokine produced by CD4 T cells that
      affects the differentiation and function of T, B, and NK cells by binding to a
      receptor consisting of the common cytokine receptor gamma chain and the IL-21
      receptor (IL-21R). IL-21, a product associated with IL-17-producing CD4 T cells
      (T(H)17) and follicular CD4 T helper cells (T(FH)), has been implicated in
      autoimmune disorders including the severe systemic lupus erythematosus (SLE)-like
      disease characteristic of BXSB-Yaa mice. To determine whether IL-21 plays a
      significant role in this disease, we compared IL-21R-deficient and -competent
      BXSB-Yaa mice for multiple parameters of SLE. The deficient mice showed none of
      the abnormalities characteristic of SLE in IL-21R-competent Yaa mice, including
      hypergammaglobulinemia, autoantibody production, reduced frequencies of marginal
      zone B cells and monocytosis, renal disease, and premature morbidity. IL-21
      production associated with this autoimmune disease was not a product of T(H)17
      cells and was not limited to conventional CXCR5(+) T(FH) but instead was produced
      broadly by ICOS(+) CD4(+) splenic T cells. IL-21 arising from an abnormal
      population of CD4 T cells is thus central to the development of this lethal
      disease, and, more generally, could play an important role in human SLE and
      related autoimmune disorders.

PMID- 19164520
TI  - FK506-binding protein (FKBP) partitions a modified HIV protease inhibitor into
      blood cells and prolongs its lifetime in vivo.
AB  - HIV protease inhibitors are a key component of anti-retroviral therapy, but their
      susceptibility to cytochrome P(450) metabolism reduces their systemic
      availability and necessitates repetitive dosing. Importantly, failure to maintain
      adequate inhibitor levels is believed to provide an opportunity for resistance to
      emerge; thus, new strategies to prolong the lifetime of these drugs are needed.
      Toward this goal, numerous prodrug approaches have been developed, but these
      methods involve creating inactive precursors that require enzymatic processing.
      Using an alternative strategy inspired by the natural product FK506, we have
      synthetically modified an HIV protease inhibitor such that it acquires high
      affinity for the abundant, cytoplasmic chaperone, FK506-binding protein (FKBP).
      This modified protease inhibitor maintains activity against HIV-1 protease
      (IC(50) = 19 nM) and, additionally, it is partitioned into the cellular component
      of whole blood via binding to FKBP. Interestingly, redistribution into this
      protected niche reduces metabolism and improves its half-life in mice by almost
      20-fold compared with the unmodified compound. Based on these findings, we
      propose that addition of FKBP-binding groups might partially overcome the poor
      pharmacokinetic properties of existing HIV protease inhibitors and, potentially,
      other drug classes.

PMID- 19164522
TI  - Market forces affect patterns of polygyny in Uganda.
AB  - Polygynous marriage is generally more beneficial for men than it is for women,
      although women may choose to marry an already-married man if he is the best
      alternative available. We use the theory of biological markets to predict that
      the likelihood of a man marrying polygynously will be a function of the level of
      resources that he has, the local sex ratio, and the resources that other men in
      the local population have. Using records of more than 1 million men in 56
      districts from the 2002 Ugandan census, we show that polygynously married men are
      more likely to own land than monogamously married men, that polygynous marriages
      become more common as the district sex ratio becomes more female biased, that
      owning land is particularly important when men are abundant in the district, and
      that a man's owning land most increases the odds of polygyny in districts where
      few other men own land. Results are discussed with reference to models of the
      evolution of polygyny.

PMID- 19164521
TI  - Long-lived Indy induces reduced mitochondrial reactive oxygen species production
      and oxidative damage.
AB  - Decreased Indy activity extends lifespan in D. melanogaster without significant
      reduction in fecundity, metabolic rate, or locomotion. To understand the
      underlying mechanisms leading to lifespan extension in this mutant strain, we
      compared the genome-wide gene expression changes in the head and thorax of adult
      Indy mutant with control flies over the course of their lifespan. A signature
      enrichment analysis of metabolic and signaling pathways revealed that expression
      levels of genes in the oxidative phosphorylation pathway are significantly lower
      in Indy starting at day 20. We confirmed experimentally that complexes I and III
      of the electron transport chain have lower enzyme activity in Indy long-lived
      flies by Day 20 and predicted that reactive oxygen species (ROS) production in
      mitochondria could be reduced. Consistently, we found that both ROS production
      and protein damage are reduced in Indy with respect to control. However, we did
      not detect significant differences in total ATP, a phenotype that could be
      explained by our finding of a higher mitochondrial density in Indy mutants. Thus,
      one potential mechanism by which Indy mutants extend life span could be through
      an alteration in mitochondrial physiology leading to an increased efficiency in
      the ATP/ROS ratio.

PMID- 19164523
TI  - The conserved NAD(H)-dependent corepressor CTBP-1 regulates Caenorhabditis
      elegans life span.
AB  - CtBP (C-terminal binding protein) is an evolutionarily conserved NAD(H)-dependent
      transcriptional corepressor, whose activity has been shown to be regulated by the
      NAD/NADH ratio. Although recent studies have provided significant new insights
      into mechanisms by which CtBP regulates transcription, the biological function of
      CtBP remains incompletely understood. Here, we report that genetic inactivation
      of the Caenorhabditis elegans homolog, ctbp-1, results in life span extension,
      which is suppressed by reintroduction of the ctbp-1 genomic DNA encoding wild
      type but not NAD(H)-binding defective CTBP-1 protein. We show that CTBP-1
      possibly modulates aging through the insulin/IGF-1 signaling pathway, dependent
      on the forkhead transcription factor DAF-16, but independent of the NAD-dependent
      histone deacetylase SIR-2.1. Genome-wide microarray analysis identifies >200
      potential CTBP-1 target genes. Importantly, RNAi inhibition of a putative
      triacylglycerol lipase gene lips-7(C09E8.2) but not another lipase suppresses the
      life span extension phenotype. Consistently, metabolic analysis shows that the
      triacylglycerol level is reduced in the ctbp-1 deletion mutant, which is restored
      to the wild-type level by RNAi inhibition of lips-7. Taken together, our data
      suggest that CTBP-1 controls life span probably through the regulation of lipid
      metabolism.

PMID- 19164524
TI  - Electron microscopy of whole cells in liquid with nanometer resolution.
AB  - Single gold-tagged epidermal growth factor (EGF) molecules bound to cellular EGF
      receptors of fixed fibroblast cells were imaged in liquid with a scanning
      transmission electron microscope (STEM). The cells were placed in buffer solution
      in a microfluidic device with electron transparent windows inside the vacuum of
      the electron microscope. A spatial resolution of 4 nm and a pixel dwell time of
      20 micros were obtained. The liquid layer was sufficiently thick to contain the
      cells with a thickness of 7 +/- 1 microm. The experimental findings are
      consistent with a theoretical calculation. Liquid STEM is a unique approach for
      imaging single molecules in whole cells with significantly improved resolution
      and imaging speed over existing methods.

PMID- 19164525
TI  - RNA-directed DNA methylation induces transcriptional activation in plants.
AB  - A class-C floral homeotic gene of Petunia, pMADS3, is specifically expressed in
      the stamen and carpels of developing flowers. We had previously reported the ect
      pMADS3 phenomenon in which introduction of a part of the pMADS3 genomic sequence,
      including intron 2, induces ectopic expression of endogenous pMADS3. Unlike
      transcriptional or posttranscriptional gene silencing triggered by the
      introduction of homologous sequences, this observation is unique in that the gene
      expression is up-regulated. In this study, we demonstrated that the ect-pMADS3
      phenomenon is due to transcriptional activation based on RNA-directed DNA
      methylation (RdDM) occurring in a particular CG in a putative cis-element in
      pMADS3 intron 2. The CG methylation was maintained over generations, along with
      pMADS3 ectopic expression, even in the absence of RNA triggers. These results
      demonstrate a previously undescribed transcriptional regulatory mechanism that
      could lead to the generation of a transcriptionally active epiallele, thereby
      contributing to plant evolution. Our results also reveal a putative negative cis
      element for organ-specific transcriptional regulation of class-C floral homeotic
      genes, which could be difficult to identify by other approaches.

PMID- 19164526
TI  - Neural signature of the conscious processing of auditory regularities.
AB  - Can conscious processing be inferred from neurophysiological measurements? Some
      models stipulate that the active maintenance of perceptual representations across
      time requires consciousness. Capitalizing on this assumption, we designed an
      auditory paradigm that evaluates cerebral responses to violations of temporal
      regularities that are either local in time or global across several seconds.
      Local violations led to an early response in auditory cortex, independent of
      attention or the presence of a concurrent visual task, whereas global violations
      led to a late and spatially distributed response that was only present when
      subjects were attentive and aware of the violations. We could detect the global
      effect in individual subjects using functional MRI and both scalp and
      intracerebral event-related potentials. Recordings from 8 noncommunicating
      patients with disorders of consciousness confirmed that only conscious
      individuals presented a global effect. Taken together these observations suggest
      that the presence of the global effect is a signature of conscious processing,
      although it can be absent in conscious subjects who are not aware of the global
      auditory regularities. This simple electrophysiological marker could thus serve
      as a useful clinical tool.

PMID- 19164527
TI  - A peroxide bridge between Fe and Cu ions in the O2 reduction site of fully
      oxidized cytochrome c oxidase could suppress the proton pump.
AB  - The fully oxidized form of cytochrome c oxidase, immediately after complete
      oxidation of the fully reduced form, pumps protons upon each of the initial 2
      single-electron reduction steps, whereas protons are not pumped during single
      electron reduction of the fully oxidized "as-isolated" form (the fully oxidized
      form without any reduction/oxidation treatment) [Bloch D, et al. (2004) The
      catalytic cycle of cytochrome c oxidase is not the sum of its two halves. Proc
      Natl Acad Sci USA 101:529-533]. For identification of structural differences
      causing the remarkable functional difference between these 2 distinct fully
      oxidized forms, the X-ray structure of the fully oxidized as-isolated bovine
      heart cytochrome c oxidase was determined at 1.95-A resolution by limiting the X
      ray dose for each shot and by using many (approximately 400) single crystals.
      This minimizes the effects of hydrated electrons induced by the X-ray
      irradiation. The X-ray structure showed a peroxide group bridging the 2 metal
      sites in the O(2) reduction site (Fe(3+)-O(-)-O(-)-Cu(2+)), in contrast to a
      ferric hydroxide (Fe(3+)-OH(-)) in the fully oxidized form immediately after
      complete oxidation from the fully reduced form, as has been revealed by resonance
      Raman analyses. The peroxide-bridged structure is consistent with the reductive
      titration results showing that 6 electron equivalents are required for complete
      reduction of the fully oxidized as-isolated form. The structural difference
      between the 2 fully oxidized forms suggests that the bound peroxide in the O(2)
      reduction site suppresses the proton pumping function.

PMID- 19164528
TI  - Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated
      cell polarization.
AB  - Nucleocytoplasmic coupling is mediated by outer nuclear membrane (ONM) nesprin
      proteins and inner nuclear membrane Sun proteins. Interactions spanning the
      perinuclear space create nesprin-Sun complexes connecting the cytoskeleton to
      nuclear components. A search for proteins displaying a conserved C-terminal
      sequence present in nesprins 1-3 identified nesprin 4 (Nesp4), a new member of
      this family. Nesp4 is a kinesin-1-binding protein that displays Sun-dependent
      localization to the ONM. Expression of Nesp4 is associated with dramatic changes
      in cellular organization involving relocation of the centrosome and Golgi
      apparatus relative to the nucleus. These effects can be accounted for entirely by
      Nesp4's kinesin-binding function. The implication is that Nesp4 may contribute to
      microtubule-dependent nuclear positioning.

PMID- 19164529
TI  - Chloroplast protein targeting involves localized translation in Chlamydomonas.
AB  - The compartmentalization of eukaryotic cells requires that newly synthesized
      proteins be targeted to the compartments in which they function. In chloroplasts,
      a few thousand proteins function in photosynthesis, expression of the chloroplast
      genome, and other processes. Most chloroplast proteins are synthesized in the
      cytoplasm, imported, and then targeted to a specific chloroplast compartment. The
      remainder are encoded by the chloroplast genome, synthesized within the
      organelle, and targeted by mechanisms that are only beginning to be elucidated.
      We used fluorescence confocal microscopy to explore the targeting mechanisms used
      by several chloroplast proteins in the green alga Chlamydomonas. These include
      the small subunit of ribulose bisphosphate carboxylase (rubisco) and the light
      harvesting complex II (LHCII) subunits, which are imported from the cytoplasm,
      and 2 proteins synthesized in the chloroplast: the D1 subunit of photosystem II
      and the rubisco large subunit. We determined whether the targeting of each
      protein involves localized translation of the mRNA that encodes it. When this was
      the case, we explored whether the targeting sequence was in the nascent
      polypeptide or in the mRNA, based on whether the localization was translation
      dependent or -independent, respectively. The results reveal 2 novel examples of
      targeting by localized translation, in LHCII subunit import and the targeting of
      the rubisco large subunit to the pyrenoid. They also demonstrate examples of each
      of the three known mechanisms-posttranslational, cotranslational (signal
      recognition particle-mediated), and mRNA-based-in the targeting of specific
      chloroplast proteins. Our findings can help guide the exploration of these
      pathways at the biochemical level.

PMID- 19164531
TI  - Conformational disturbance in Abl kinase upon mutation and deregulation.
AB  - Protein dynamics are inextricably linked to protein function but there are few
      techniques that allow protein dynamics to be conveniently interrogated. For
      example, mutations and translocations give rise to aberrant proteins such as Bcr
      Abl where changes in protein conformation and dynamics are believed to result in
      deregulated kinase activity that provides the oncogenic signal in chronic
      myelogeous leukemia. Although crystal structures of the down-regulated c-Abl
      kinase core have been reported, the conformational impact of mutations that
      render Abl resistant to small-molecule kinase inhibitors are largely unknown as
      is the allosteric interplay of the various regulatory elements of the protein.
      Hydrogen exchange mass spectrometry (HX MS) was used to compare the conformations
      of wild-type Abl with a nonmyristoylated form and with 3 clinically relevant
      imatinib resistance mutants (T315I, Y253H and E255V). A HX-resistant core
      localized to the interface between the SH2 and kinase domains, a region known to
      be important for maintaining the down-regulated state. Conformational differences
      upon demyristoylation were consistent with the SH2 domain moving to the top of
      the small lobe of the kinase domain as a function of activation. There were
      conformational changes in the T315I mutant but, surprisingly, no major changes in
      conformation were detected in either the Y253H or the E255V mutants. Taken
      together, these results provide evidence that allosteric interactions and
      conformational changes play a major role in Abl kinase regulation in solution.
      Similar analyses could be performed on any protein to provide mechanistic details
      about conformational changes and protein function.

PMID- 19164530
TI  - Two proteolytic pathways regulate DNA repair by cotargeting the Mgt1 alkylguanine
      transferase.
AB  - O(6)-methylguanine (O(6)meG) and related modifications of guanine in double
      stranded DNA are functionally severe lesions that can be produced by many
      alkylating agents, including N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a
      potent carcinogen. O(6)meG is repaired through its demethylation by the O(6)
      alkylguanine-DNA alkyltransferase (AGT). This protein is called Mgmt (or MGMT) in
      mammals and Mgt1 in the yeast Saccharomyces cerevisiae. AGT proteins remove
      methyl and other alkyl groups from an alkylated O(6) in guanine by transferring
      the adduct to an active-site cysteine residue. The resulting S-alkyl-Cys of AGT
      is not restored back to Cys, so repair proteins of this kind can act only once.
      We report here that S. cerevisiae Mgt1 is cotargeted for degradation, through a
      degron near its N terminus, by 2 ubiquitin-mediated proteolytic systems, the
      Ubr1/Rad6-dependent N-end rule pathway and the Ufd4/Ubc4-dependent ubiquitin
      fusion degradation (UFD) pathway. The cotargeting of Mgt1 by these pathways is
      synergistic, in that it increases not only the yield of polyubiquitylated Mgt1,
      but also the processivity of polyubiquitylation. The N-end rule and UFD pathways
      comediate both the constitutive and MNNG-accelerated degradation of Mgt1. Yeast
      cells lacking the Ubr1 and Ufd4 ubiquitin ligases were hyperresistant to MNNG but
      hypersensitive to the toxicity of overexpressed Mgt1. We consider ramifications
      of this discovery for the control of DNA repair and mechanisms of substrate
      targeting by the ubiquitin system.

PMID- 19164532
TI  - Clathrin adaptor AP-1 complex excludes multiple postsynaptic receptors from axons
      in C. elegans.
AB  - Neurons are highly polarized cells with morphologically and molecularly distinct
      axonal and dendritic compartments. It is not well understood how postsynaptic
      receptors are selectively enriched in dendrites in vivo. We investigated the
      molecular mechanisms of dendritically polarized localization of a glutamate
      receptor, an acetylcholine receptor, and a ROR-type receptor tyrosine kinase in
      the interneuron RIA in C. elegans. We found that the clathrin adaptor AP-1
      complex mu1 subunit UNC-101 functions cell autonomously to maintain the correct
      localization of these receptors in a dynamin-dependent manner. In unc-101
      mutants, instead of being dendritically enriched, all 3 receptors are evenly
      distributed in the axonal and dendritic compartments. Surprisingly, UNC-101
      predominantly localizes to the axonal compartment, suggesting a possible
      transcytosis model for the dendritic targeting of neurotransmitter receptors.

PMID- 19164534
TI  - The fifth class of Galpha proteins.
AB  - All alpha-subunits of vertebrate heterotrimeric G proteins have been classified
      into 4 major classes, Gs, Gi, Gq, and G12, which possess orthologs already in
      sponges, one of the earliest animal phyla to evolve. Here we report the discovery
      of the fifth class of Galpha protein, Gv, ancient like the other 4 classes, with
      members already in sponges, and encoded by 1-2 gnav genes per species. Gv is
      conserved across the animal kingdom including vertebrates, arthropods, mollusks,
      and annelids, but has been lost in many lineages such as nematodes, fruit fly,
      jawless fish, and tetrapods, concordant with a birth-and-death mode of evolution.
      All Gv proteins contain 5 G-box motifs characteristic of GTP-binding proteins and
      the expected acylation consensus sites in the N-terminal region. Sixty amino acid
      residues are conserved only among Gv, suggesting that they may constitute
      interaction sites for Gv-specific partner molecules. Overall Gv homology is high,
      on average 70% amino acid identity among vertebrate family members. The d(N)/d(S)
      analysis of teleost gnav genes reveals evolution under stringent negative
      selection. Genomic structure of vertebrate gnav genes is well conserved and
      different from those of the other 4 classes. The predicted full ORF of zebrafish
      gnav1 was confirmed by isolation from cDNA. RT-PCR analysis showed broad
      expression of gnav1 in adult zebrafish and in situ hybridization demonstrated a
      more restricted expression in larval tissues including the developing inner ear.
      The discovery of this fifth class of Galpha proteins changes our understanding of
      G protein evolution.

PMID- 19164533
TI  - Integrin alphavbeta1 promotes infection by human metapneumovirus.
AB  - Human metapneumovirus (hMPV) is a recently described paramyxovirus that causes
      lower respiratory infections in children and adults worldwide. The hMPV fusion
      (F) protein is a membrane-anchored glycoprotein and major protective antigen. All
      hMPV F protein sequences determined to date contain an Arg-Gly-Asp (RGD)
      sequence, suggesting that F engages RGD-binding integrins to mediate cell entry.
      The divalent cation chelator EDTA, which disrupts heterodimeric integrin
      interactions, inhibits infectivity of hMPV but not the closely related
      respiratory syncytial virus (RSV), which lacks an RGD motif. Function-blocking
      antibodies specific for alphavbeta1 integrin inhibit infectivity of hMPV but not
      RSV. Transfection of nonpermissive cells with alphav or beta1 cDNAs confers hMPV
      infectivity, whereas reduction of alphav and beta1 integrin expression by siRNA
      inhibits hMPV infection. Recombinant hMPV F protein binds to cells, whereas Arg
      Gly-Glu (RGE)-mutant F protein does not. These data suggest that alphavbeta1
      integrin is a functional receptor for hMPV.

PMID- 19164535
TI  - Negative regulation of Caenorhabditis elegans epidermal damage responses by death
      associated protein kinase.
AB  - Wounding of epidermal layers triggers multiple coordinated responses to damage.
      We show here that the Caenorhabditis elegans ortholog of the tumor suppressor
      death-associated protein kinase, dapk-1, acts as a previously undescribed
      negative regulator of barrier repair and innate immune responses to wounding.
      Loss of DAPK-1 function results in constitutive formation of scar-like structures
      in the cuticle, and up-regulation of innate immune responses to damage.
      Overexpression of DAPK-1 represses innate immune responses to needle wounding. Up
      regulation of innate immune responses in dapk-1 requires the TIR-1/p38 signal
      transduction pathway; loss of function in this pathway synergizes with dapk-1 to
      drastically reduce adult lifespan. Our results reveal a previously undescribed
      function for the DAPK tumor suppressor family in regulation of epithelial damage
      responses.

PMID- 19164536
TI  - Sensory transmission in cerebellar granule cells relies on similarly coded mossy
      fiber inputs.
AB  - The computational principles underlying the processing of sensory-evoked synaptic
      inputs are understood only rudimentarily. A critical missing factor is knowledge
      of the activation patterns of the synaptic inputs to the processing neurons. Here
      we use well-defined, reproducible skin stimulation to describe the specific
      signal transformations that occur in different parallel mossy fiber pathways and
      analyze their representation in the synaptic inputs to cerebellar granule cells.
      We find that mossy fiber input codes are preserved in the synaptic responses of
      granule cells, suggesting a coding-specific innervation. The computational
      consequences of this are that it becomes possible for granule cells to also
      transmit weak sensory inputs in a graded fashion and to preserve the specific
      activity patterns of the mossy fibers.

PMID- 19164537
TI  - Congenitally altered motor experience alters somatotopic organization of human
      primary motor cortex.
AB  - Human motor development is thought to result from a complex interaction between
      genes and experience. The well-known somatotopic organization of the primate
      primary motor cortex (M1) emerges postnatally. Although adaptive changes in
      response to learning and use occur throughout life, somatotopy is maintained as
      reorganization is restricted to modifications within major body part
      representations. We report of a unique opportunity to evaluate the influence of
      experience on the genetically determined somatotopic organization of motor cortex
      in humans. We examined the motor "foot" representation in subjects with
      congenitally compromised hand function and compensatory skillful foot use.
      Functional magnetic resonance imaging (fMRI) and transcranial magnetic
      stimulation (TMS) of M1 revealed that the foot was represented in the classical
      medial foot area of M1 and was several centimetres away in nonadjacent cortex in
      the vicinity of the lateral "hand" area. Both areas had direct output to the
      spinal motor neurons innervating foot muscles and were behaviorally relevant
      because experimental disruption of either area by TMS altered reaction times. We
      demonstrate a unique, nonsomatotopically organized M1 in humans, which emerged as
      a function of grossly altered motor behavior from the earliest stages of
      development. Our results imply that during early motor development experience may
      play a more critical role in the shaping of genetically determined neural
      networks than previously assumed.

PMID- 19164538
TI  - A helix-to-coil transition at the epsilon-cut site in the transmembrane dimer of
      the amyloid precursor protein is required for proteolysis.
AB  - Processing of amyloid precursor protein (APP) by gamma-secretase is the last step
      in the formation of the Abeta peptides associated Alzheimer's disease. Solid
      state NMR spectroscopy is used to establish the structural features of the
      transmembrane (TM) and juxtamembrane (JM) domains of APP that facilitate
      proteolysis. Using peptides corresponding to the APP TM and JM regions (residues
      618-660), we show that the TM domain forms an alpha-helical homodimer mediated by
      consecutive GxxxG motifs. We find that the APP TM helix is disrupted at the
      intracellular membrane boundary near the epsilon-cleavage site. This helix-to
      coil transition is required for gamma-secretase processing; mutations that extend
      the TM alpha-helix inhibit epsilon cleavage, leading to a low production of Abeta
      peptides and an accumulation of the alpha- and beta-C-terminal fragments. Our
      data support a progressive cleavage mechanism for APP proteolysis that depends on
      the helix-to-coil transition at the TM-JM boundary and unraveling of the TM alpha
      helix.

PMID- 19164539
TI  - Characterization of the thymic IL-7 niche in vivo.
AB  - The thymus represents the "cradle" for T cell development, with thymic stroma
      providing multiple soluble and membrane cues to developing thymocytes. Although
      IL-7 is recognized as an essential factor for thymopoiesis, the "environmental
      niche" of thymic IL-7 activity remains poorly characterized in vivo. Using
      bacterial artificial chromosome transgenic mice in which YFP is under control of
      IL-7 promoter, we identify a subset of thymic epithelial cells (TECs) that co
      express YFP and high levels of Il7 transcripts (IL-7(hi) cells). IL-7(hi) TECs
      arise during early fetal development, persist throughout life, and co-express
      homeostatic chemokines (Ccl19, Ccl25, Cxcl12) and cytokines (Il15) that are
      critical for normal thymopoiesis. In the adult thymus, IL-7(hi) cells localize to
      the cortico-medullary junction and display traits of both cortical and medullary
      TECs. Interestingly, the frequency of IL-7(hi) cells decreases with age,
      suggesting a mechanism for the age-related thymic involution that is associated
      with declining IL-7 levels. Our temporal-spatial analysis of IL-7-producing cells
      in the thymus in vivo suggests that thymic IL-7 levels are dynamically regulated
      under distinct physiological conditions. This IL-7 reporter mouse provides a
      valuable tool to further dissect the mechanisms that govern thymic IL-7
      expression in vivo.

PMID- 19164540
TI  - Echoes of a salty exchange.

PMID- 19164541
TI  - Molecular recognition and self-assembly special feature: Self-assembled
      biomimetic [2Fe2S]-hydrogenase-based photocatalyst for molecular hydrogen
      evolution.
AB  - The large-scale production of clean energy is one of the major challenges society
      is currently facing. Molecular hydrogen is envisaged as a key green fuel for the
      future, but it becomes a sustainable alternative for classical fuels only if it
      is also produced in a clean fashion. Here, we report a supramolecular biomimetic
      approach to form a catalyst that produces molecular hydrogen using light as the
      energy source. It is composed of an assembly of chromophores to a bis(thiolate)
      bridged diiron ([2Fe2S]) based hydrogenase catalyst. The supramolecular building
      block approach introduced in this article enabled the easy formation of a series
      of complexes, which are all thoroughly characterized, revealing that the
      photoactivity of the catalyst assembly strongly depends on its nature. The active
      species, formed from different complexes, appears to be the [Fe(2)(micro
      pdt)(CO)(4){PPh(2)(4-py)}(2)] (3) with 2 different types of porphyrins (5a and
      5b) coordinated to it. The modular supramolecular approach was important in this
      study as with a limited number of building blocks several different complexes
      were generated.

PMID- 19164543
TI  - Visualizing the protein synthesis machinery: new focus on the translational
      GTPase elongation factor Tu.

PMID- 19164542
TI  - X chromosome inactivation in the absence of Dicer.
AB  - Dicer is central to the RNA interference (RNAi) pathway, because it is required
      for processing of double-stranded RNA (dsRNA) precursors into small RNA effector
      molecules. In principle, any long dsRNA could serve as a substrate for Dicer. The
      X inactive specific transcript (Xist) is an untranslated RNA that is required for
      dosage compensation in mammals. It coats and silences 1 of the 2 X chromosomes in
      female cells and initiates a chromosomewide change in chromatin structure that
      includes the recruitment of Polycomb proteins, but it is largely unknown how Xist
      RNA mediates these processes. To investigate a potential link between the RNAi
      pathway and X inactivation, we generated and analyzed Dicer-deficient embryonic
      stem (ES) cells. In the absence of Dicer, coating by Xist RNA, initiation of
      silencing, and recruitment of Polycomb proteins occur normally. Dicer ablation
      had modest effects on the steady-state levels of spliced Xist RNA. Together our
      data indicate that the RNAi machinery is not essential for the initiation of X
      inactivation.

PMID- 19164544
TI  - Expanding the repertoire of biofuel alternatives through metabolic pathway
      evolution.

PMID- 19164546
TI  - A step closer to visualizing the electron-phonon interplay in real time.

PMID- 19164545
TI  - Erythropoietin modulation of astrocyte water permeability as a component of
      neuroprotection.
AB  - Disturbed brain water homeostasis with swelling of astroglial cells is a common
      complication in stroke, trauma, and meningitis and is considered to be a major
      cause of permanent brain damage. Astroglial cells possess the water channel
      aquaporin 4 (AQP4). Recent studies from our laboratory have shown that glutamate,
      acting on group I metabotropic glutamate receptors (mGluRs), increases the
      permeability of astrocyte AQP4, which, in situations of hypoxia-ischemia, will
      increase astrocyte water uptake. Here we report that erythropoietin (EPO), which
      in recent years has emerged as a potent neuro-protective agent, antagonizes the
      effect of a group I mGluR agonist on astrocyte water permeability. Activation of
      group I mGluRs triggers fast and highly regular intracellular calcium
      oscillations and we show that EPO interferes with this signaling event by
      altering the frequency of the oscillations. These effects of EPO are immediate,
      in contrast to the neuroprotective effects of EPO that are known to depend upon
      gene activation. Our findings indicate that EPO may directly reduce the risk of
      astrocyte swelling in stroke and other brain insults. In support of this
      conclusion we found that EPO reduced the neurological symptoms in a mouse model
      of primary brain edema known to depend upon AQP4 water transport.

PMID- 19164547
TI  - Role of calcium-independent phospholipase A2 in the pathogenesis of Barth
      syndrome.
AB  - Quantitative and qualitative alterations of mitochondrial cardiolipin have been
      implicated in the pathogenesis of Barth syndrome, an X-linked cardioskeletal
      myopathy caused by a deficiency in tafazzin, an enzyme in the cardiolipin
      remodeling pathway. We have generated and previously reported a tafazzin
      deficient Drosophila model of Barth syndrome that is characterized by low
      cardiolipin concentration, abnormal cardiolipin fatty acyl composition, abnormal
      mitochondria, and poor motor function. Here, we first show that tafazzin
      deficiency in Drosophila disrupts the final stage of spermatogenesis, spermatid
      individualization, and causes male sterility. This phenotype can be genetically
      suppressed by inactivation of the gene encoding a calcium-independent
      phospholipase A(2), iPLA2-VIA, which also prevents cardiolipin
      depletion/monolysocardiolipin accumulation, although in wild-type flies
      inactivation of the iPLA2-VIA does not affect the molecular composition of
      cardiolipin. Furthermore, we show that treatment of Barth syndrome patients'
      lymphoblasts in tissue culture with the iPLA(2) inhibitor, bromoenol lactone,
      partially restores their cardiolipin homeostasis. Taken together, these findings
      establish a causal role of cardiolipin deficiency in the pathogenesis of Barth
      syndrome and identify iPLA2-VIA as an important enzyme in cardiolipin
      deacylation, and as a potential target for therapeutic intervention.

PMID- 19164549
TI  - Nonparametric entrainment of the in vitro circadian phosphorylation rhythm of
      cyanobacterial KaiC by temperature cycle.
AB  - The three cyanobacterial Kai proteins and ATP are capable of generating an
      autonomous rhythm of KaiC phosphorylation in a test tube. As the period is
      approximately 24 hours and is stable in a wide temperature range, this rhythm is
      thought to function as the basic oscillator of the cyanobacterial circadian
      system. We have examined the rhythm under various temperature cycles and found
      that it was stably entrained by a temperature cycle of 20-28 hours. As the period
      length was not altered by temperature, entrainment by period change could be
      excluded from possible mechanisms. Instead, temperature steps between 30 degrees
      and 45 degrees C and vice versa shifted the phase of the rhythm in a phase
      dependent manner. Based on the phase response curves of the step-up and step-down
      in temperature, phase shift by single temperature pulse was estimated using a
      nonparametric entrainment model (discontinuous phase jump by external stimuli).
      The predicted phase shift was consistent with the experimentally measured phase
      shift. Next, successive phase shifts caused by repeated temperature cycles were
      computed by two phase response curves and compared with actual entrainment of the
      rhythm. As the entrainment pattern observed after various combinations of
      temperature cycles matched the prediction, it is likely that nonparametric
      entrainment functions even in the simple three-protein system. We also analyzed
      entrainment of KaiC phosphorylation by temperature cycle in cyanobacterial cells
      and found both the parametric and the nonparametric models function in vivo.

PMID- 19164548
TI  - A critical role for the sphingosine analog AAL-R in dampening the cytokine
      response during influenza virus infection.
AB  - Pulmonary tissue damage resulting from influenza virus infection is caused by
      both the cytolytic activity of the virus and the host immune response. Immune
      mediated injury results from T cell-mediated destruction of virus-infected cells
      and by release of cytokines and chemokines that attract polymorphonuclear
      leukocytes (PML) and macrophages to the infected site. The cytokines/chemokines
      potentiate dendritic cell (DC) activation and T cell expansion, which further
      enhances local damage. Here we report that immune modulation by local
      administration to the respiratory tract of sphingosine analog AAL-R significantly
      dampens the release of cytokines and chemokines while maintaining protective
      neutralizing antibody and cytotoxic T cell responses. As a result there was a
      marked reduction of infiltrating PML and macrophages into the lung and resultant
      pulmonary tissue injury. DC maturation was suppressed, which limited
      proliferation of specific antiviral T cells in the lung and draining lymph nodes.
      Further, AAL-R was effective in controlling CD8(+) T cell accumulation in the
      lungs even when given 4 days after initiation of influenza virus infection. These
      data indicate that sphingosine analogs display useful potential for controlling
      the immunopathology caused by influenza virus.

PMID- 19164550
TI  - Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at
      mitochondria.
AB  - gC1qR is one of the C1q receptors implicated in the regulation of innate and
      adaptive immunity. We found that gC1qR inhibits RIG-I and MDA5-dependent
      antiviral signaling. Double stranded RNA and virus trigger the translocation of
      gC1qR to the mitochondrial outer membrane leading to the interaction of gC1qR
      with the RIG-I and MDA5 adaptor, VISA/MAVS/IPS-1/Cardif. The interaction of gC1qR
      with VISA/MAVS/IPS-1/Cardif at mitochondria results in the disruption of RIG-I
      and MDA5 signaling and the promotion of virus replication. Knockdown of
      endogenous gC1qR enhances RIG-I-dependent antiviral signaling, and augments the
      inhibition of virus proliferation. Therefore, gC1qR is a physiological inhibitor
      of the RIG-I and MDA5-mediated antiviral signaling pathway. These data uncover a
      new viral mechanism used to negatively control antiviral signaling in host cells.

PMID- 19164551
TI  - Circadian oscillation of nucleotide excision repair in mammalian brain.
AB  - The circadian clock regulates the daily rhythms in the physiology and behavior of
      many organisms, including mice and humans. These cyclical changes at molecular
      and macroscopic levels affect the organism's response to environmental stimuli
      such as light and food intake and the toxicity and efficacy of chemo- and
      radiotherapeutic agents. In this work, we investigated the circadian behavior of
      the nucleotide excision repair capacity in the mouse cerebrum to gain some
      insight into the optimal circadian time for favorable therapeutic response with
      minimal side effects in cancer treatment with chemotherapeutic drugs that produce
      bulky adducts in DNA. We find that nucleotide excision repair activity in the
      mouse cortex is highest in the afternoon/evening hours and is at its lowest in
      the night/early morning hours. The circadian oscillation of the repair capacity
      is caused at least in part by the circadian oscillation of the xeroderma
      pigmentosum A DNA damage recognition protein.

PMID- 19164552
TI  - Infectious bursal disease virus is an icosahedral polyploid dsRNA virus.
AB  - Viruses are a paradigm of the economy of genome resources, reflected in their
      multiplication strategy and for their own structure. Although there is enormous
      structural diversity, the viral genome is always enclosed within a proteinaceous
      coat, and most virus species are haploid; the only exception to this rule are the
      highly pleomorphic enveloped viruses. We performed an in-depth characterization
      of infectious bursal disease virus (IBDV), a non-enveloped icosahedral dsRNA
      virus with a bisegmented genome. Up to 6 natural populations can be purified,
      which share a similar protein composition but show higher sedimentation
      coefficients as particle density increases. Stoichiometry analysis of their
      genome indicated that these biophysical differences correlate with the copy
      number of dsRNA segments inside the viral capsid. This is a demonstration of a
      functional polyploid icosahedral dsRNA virus. We show that IBDV particles with
      greater genome copy number have higher infectivity rates. Our results show an
      unprecedented replicative strategy for dsRNA viruses and suggest that
      birnaviruses are living viral entities encompassing numerous functional and
      structural characteristics of positive and negative ssRNA viruses.

PMID- 19164554
TI  - Disulfide bond formation by exported glutaredoxin indicates glutathione's
      presence in the E. coli periplasm.
AB  - Organisms have evolved elaborate systems that ensure the homeostasis of the thiol
      redox environment in their intracellular compartments. In Escherichia coli, the
      cytoplasm is kept under reducing conditions by the thioredoxins with the help of
      thioredoxin reductase and the glutaredoxins with the small molecule glutathione
      and glutathione reductase. As a result, disulfide bonds are constantly resolved
      in this compartment. In contrast to the cytoplasm, the periplasm of E. coli is
      maintained in an oxidized state by DsbA, which is recycled by DsbB. Thioredoxin
      1, when exported to the periplasm turns from a disulfide bond reductase to an
      oxidase that, like DsbA, is dependent on DsbB. In this study we set out to
      investigate whether a subclass of the thioredoxin superfamily, the glutaredoxins,
      can become disulfide bond-formation catalysts when they are exported to the
      periplasm. We find that glutaredoxins can promote disulfide bond formation in the
      periplasm. However, contrary to the behavior of thioredoxin 1 in this
      environment, the glutaredoxins do so independently of DsbB. Furthermore, we show
      that glutaredoxin 3 requires the glutathione biosynthesis pathway for its
      function and can oxidize substrates with only a single active-site cysteine. Our
      data provides in vivo evidence suggesting that oxidized glutathione is present in
      the E. coli periplasm in biologically significant concentrations.

PMID- 19164553
TI  - Induction of TLR4-target genes entails calcium/calmodulin-dependent regulation of
      chromatin remodeling.
AB  - Upon toll-like receptor 4 (TLR4) signaling in macrophages, the mammalian Swi/Snf
      like BAF chromatin remodeling complex is recruited to many TLR4 target genes
      where it remodels their chromatin to promote transcription. Here, we show that,
      surprisingly, recruitment is not sufficient for chromatin remodeling; a second
      event, dependent on calcium/calmodulin (CaM), is additionally required.
      Calcium/CaM directly binds the HMG domain of the BAF57 subunit within the BAF
      complex. Calcium/CaM antagonists, including a CaM-binding peptide derived from
      BAF57, abolish BAF-dependent remodeling and gene expression without compromising
      BAF recruitment. BAF57 RNAi and BAF57 dominant negative mutants defective in CaM
      binding similarly impair the induction of BAF target genes. Our data implicate
      calcium/CaM in TLR4 signaling, and reveal a previously undescribed, recruitment
      independent mode of regulation of the BAF complex that is probably achieved
      through a direct CaM-BAF interaction.

PMID- 19164555
TI  - Adipokinetic hormone signaling through the gonadotropin-releasing hormone
      receptor modulates egg-laying in Caenorhabditis elegans.
AB  - In mammals, hypothalamic gonadotropin-releasing hormone (GnRH) is a neuropeptide
      that stimulates the release of gonadotropins from the anterior pituitary. The
      existence of a putative functional equivalent of this reproduction axis in
      protostomian invertebrates has been a matter of debate. In this study, the ligand
      for the GnRH receptor in the nematode Caenorhabditis elegans (Ce-GnRHR) was found
      using a bioinformatics approach. The peptide and its precursor are reminiscent of
      both insect adipokinetic hormones and GnRH-preprohormone precursors from
      tunicates and higher vertebrates. We cloned the AKH-GnRH-like preprohormone and
      the Ce-GnRHR and expressed the GPCR in HEK293T cells. The GnRHR was activated by
      the C. elegans AKH-GnRH-like peptide (EC(50) = 150 nM) and by Drosophila AKH and
      other nematode AKH-GnRHs that we found in EST databases. Analogous to both insect
      AKH receptor and vertebrate GnRH receptor signaling, Ce-AKH-GnRH activated its
      receptor through a Galpha(q) protein with Ca(2+) as a second messenger. Gene
      silencing of Ce-GnRHR, Ce-AKH-GnRH, or both resulted in a delay in the egg-laying
      process, comparable to a delay in puberty in mammals lacking a normal dose of
      GnRH peptide or with a mutated GnRH precursor or receptor gene. The present data
      support the view that the AKH-GnRH signaling system probably arose very early in
      metazoan evolution and that its role in reproduction might have been developed
      before the divergence of protostomians and deuterostomians.

PMID- 19164556
TI  - Probing deeper into first American studies.
AB  - The initial peopling of the Americas has proved one of the most challenging
      episodes in reconstructing global prehistory, challenging because researchers
      struggle with the vagaries of early archaeological site preservation, and debates
      continue over the date and place of human entry, the rapidity and direction of
      dispersion, and the variety of cultural responses to climatic change during the
      terminal Pleistocene period. Despite many recent advances in our understanding of
      these issues, especially in the areas of genetics and new archaeological
      discoveries, the field continues facing limitations in the sampling and quality
      of data, the research problems defined, and the epistemologies and theories
      applied. Theoretical development of first American studies has been uneven, and
      its contribution to global issues of early human migration has been restricted.
      This essay discusses what is known and not known about the process of the first
      peopling of the Americas from the perspective of archaeology, genetics, and
      bioanthropology. Some approaches to fill voids in data, methods, and the broader
      conceptualization of the process also are considered.

PMID- 19164557
TI  - KIT kinase mutants show unique mechanisms of drug resistance to imatinib and
      sunitinib in gastrointestinal stromal tumor patients.
AB  - Most gastrointestinal stromal tumors (GISTs) exhibit aberrant activation of the
      receptor tyrosine kinase (RTK) KIT. The efficacy of the inhibitors imatinib
      mesylate and sunitinib malate in GIST patients has been linked to their
      inhibition of these mutant KIT proteins. However, patients on imatinib can
      acquire secondary KIT mutations that render the protein insensitive to the
      inhibitor. Sunitinib has shown efficacy against certain imatinib-resistant
      mutants, although a subset that resides in the activation loop, including
      D816H/V, remains resistant. Biochemical and structural studies were undertaken to
      determine the molecular basis of sunitinib resistance. Our results show that
      sunitinib targets the autoinhibited conformation of WT KIT and that the D816H
      mutant undergoes a shift in conformational equilibrium toward the active state.
      These findings provide a structural and enzymologic explanation for the
      resistance profile observed with the KIT inhibitors. Prospectively, they have
      implications for understanding oncogenic kinase mutants and for circumventing
      drug resistance.

PMID- 19164558
TI  - RNA repair restores hemoglobin expression in IVS2-654 thalassemic mice.
AB  - Repair of beta-globin pre-mRNA rendered defective by a thalassemia-causing
      splicing mutation, IVS2-654, in intron 2 of the human beta-globin gene was
      accomplished in vivo in a mouse model of IVS2-654 thalassemia. This was effected
      by a systemically delivered splice-switching oligonucleotide (SSO), a morpholino
      oligomer conjugated to an arginine-rich peptide. The SSO blocked the aberrant
      splice site in the targeted pre-mRNA and forced the splicing machinery to
      reselect existing correct splice sites. Repaired beta-globin mRNA restored
      significant amounts of hemoglobin in the peripheral blood of the IVS2-654 mouse,
      improving the number and quality of erythroid cells.

PMID- 19164559
TI  - Effects of linker sequences on vesicle fusion mediated by lipid-anchored DNA
      oligonucleotides.
AB  - Synthetic lipid-oligonucleotide conjugates inserted into lipid vesicles mediate
      fusion when one population of vesicles displays the 5'-coupled conjugate and the
      other the 3'-coupled conjugate, so that anti-parallel hybridization allows the
      membrane surfaces to come into close proximity. Improved assays show that lipid
      mixing proceeds more quickly and to a much greater extent than content mixing,
      suggesting the latter is rate limiting. To test the effect of membrane-membrane
      spacing on fusion, a series of conjugates was constructed by adding 2-24
      noncomplementary bases at the membrane-proximal ends of two complementary
      sequences. Increasing linker lengths generally resulted in progressively reduced
      rates and extents of lipid and content mixing, in contrast to higher vesicle
      docking rates. The relatively flexible, single-stranded DNA linker facilitates
      docking but allows greater spacing between the vesicles after docking, thus
      making the transition into fusion less probable, but not preventing it
      altogether. These experiments demonstrate the utility of DNA as a model system
      for fusion proteins, where sequence can easily be modified to systematically
      probe the effect of distance between bilayers in the fusion reaction.

PMID- 19164561
TI  - FGF-dependent left-right asymmetry patterning in zebrafish is mediated by Ier2
      and Fibp1.
AB  - Establishment of left-right asymmetry in vertebrates requires nodal, Wnt-PCP and
      FGF signaling and involves ciliogenesis in a laterality organ. Effector genes
      through which FGF signaling affects laterality have not been described. We
      isolated the zebrafish ier2 and fibp1 genes as FGF target genes and show that
      their protein products interact. Knock down of these factors interferes with
      establishment of organ laterality and causes defective cilia formation in
      Kupffer's Vesicle, the zebrafish laterality organ. Cilia are also lost after
      suppression of FGF8, but can be rescued by injection of ier2 and fibp1 mRNA. We
      conclude that Ier2 and Fibp1 mediate FGF signaling in ciliogenesis in Kupffer's
      Vesicle and in the establishment of laterality in the zebrafish embryo.

PMID- 19164562
TI  - Nitric oxide and TNF-alpha trigger colonic inflammation and carcinogenesis in
      Helicobacter hepaticus-infected, Rag2-deficient mice.
AB  - Recombinase-activating gene-2-deficient (Rag2(-/-)) mice lacking functional
      lymphocytes provide a useful model of chronic inflammatory bowel disease
      emulating events in human colon cancer. Infection of Rag2(-/-) mice with
      Helicobacter hepaticus led to accumulation of macrophages and neutrophils in the
      colon, a process temporally related to up-regulation of tissue inducible nitric
      oxide synthase (iNOS) expression at the site of infection and increased nitric
      oxide (NO) production, as evidenced by urinary excretion of nitrate. Progressive
      development of increasingly severe inflammation, hyperplasia, dysplasia, and
      cancer accompanied these changes. Concurrent administration of an iNOS inhibitor
      prevented NO production and abrogated epithelial pathology and inhibited the
      onset of cancer. The presence of Gr-1(+) neutrophils and elevated tumor necrosis
      factor-alpha (TNF-alpha) expression in colon were required for increased iNOS
      expression and cancer, whereas interleukin-10 (IL-10) down-regulated TNF-alpha
      and iNOS expression and suppressed cancer. Anti-inflammatory CD4(+) regulatory
      lymphocytes also down-regulated iNOS and reduced cancer formation. Collectively,
      these results confirm essential roles for inflammation, increased TNF-alpha
      expression, and elevated NO production in colon carcinogenesis.

PMID- 19164563
TI  - Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to
      thyroid cancer.
AB  - Prior work has shown that heterozygosity G/C of single nucleotide polymorphism
      (SNP rs2910164) within the precursor of microRNA-146a predisposes to PTC (odds
      ratio = 1.62, P = 0.000007) although the mechanism was unclear. Here, we show
      that GC heterozygotes differ from both GG and CC homozygotes by producing 3
      mature microRNAs: 1 from the leading strand (miR-146a), and 2 from the passenger
      strand (miR-146a*G and miR-146a*C), each with its distinct set of target genes.
      TaqMan analysis of paired tumor/normal samples revealed 1.5- to 2.6-fold
      overexpression of polymorphic miR-146a* in 7 of 8 tumors compared with the
      unaffected part of the same gland. The microarray data showed that widely
      different transcriptomes occurred in the tumors and in unaffected parts of the
      thyroid from GC and GG patients. The modulated genes are mainly involved in
      regulation of apoptosis leading to exaggerated DNA-damage response in
      heterozygotes potentially explaining the predisposition to cancer. We propose
      that contrary to previously held views transcripts from the passenger strand of
      miRs can profoundly affect the downstream effects. Heterozygosity for
      polymorphisms within the premiR sequence can cause epistasis through the
      production of additional mature miRs. We propose that mature miRs from the
      passenger strand may regulate many genetic processes.

PMID- 19164564
TI  - Environmental change and economic development in coastal Peru between 5,800 and
      3,600 years ago.
AB  - Between approximately 5,800 and 3,600 cal B.P. the biggest architectural
      monuments and largest settlements in the Western Hemisphere flourished in the
      Supe Valley and adjacent desert drainages of the arid Peruvian coast. Intensive
      net fishing, irrigated orchards, and fields of cotton with scant comestibles
      successfully sustained centuries of increasingly complex societies that did not
      use ceramics or loom-based weaving. This unique socioeconomic adaptation was
      abruptly abandoned and gradually replaced by societies more reliant on food
      crops, pottery, and weaving. Here, we review evidence and arguments for a severe
      cycle of natural disasters-earthquakes, El Nino flooding, beach ridge formation,
      and sand dune incursion-at approximately 3,800 B.P. and hypothesize that ensuing
      physical changes to marine and terrestrial environments contributed to the demise
      of early Supe settlements.

PMID- 19164560
TI  - Human gut microbiota in obesity and after gastric bypass.
AB  - Recent evidence suggests that the microbial community in the human intestine may
      play an important role in the pathogenesis of obesity. We examined 184,094
      sequences of microbial 16S rRNA genes from PCR amplicons by using the 454
      pyrosequencing technology to compare the microbial community structures of 9
      individuals, 3 in each of the categories of normal weight, morbidly obese, and
      post-gastric-bypass surgery. Phylogenetic analysis demonstrated that although the
      Bacteria in the human intestinal community were highly diverse, they fell mainly
      into 6 bacterial divisions that had distinct differences in the 3 study groups.
      Specifically, Firmicutes were dominant in normal-weight and obese individuals but
      significantly decreased in post-gastric-bypass individuals, who had a
      proportional increase of Gammaproteobacteria. Numbers of the H(2)-producing
      Prevotellaceae were highly enriched in the obese individuals. Unlike the highly
      diverse Bacteria, the Archaea comprised mainly members of the order
      Methanobacteriales, which are H(2)-oxidizing methanogens. Using real-time PCR, we
      detected significantly higher numbers of H(2)-utilizing methanogenic Archaea in
      obese individuals than in normal-weight or post-gastric-bypass individuals. The
      coexistence of H(2)-producing bacteria with relatively high numbers of H(2)
      utilizing methanogenic Archaea in the gastrointestinal tract of obese individuals
      leads to the hypothesis that interspecies H(2) transfer between bacterial and
      archaeal species is an important mechanism for increasing energy uptake by the
      human large intestine in obese persons. The large bacterial population shift seen
      in the post-gastric-bypass individuals may reflect the double impact of the gut
      alteration caused by the surgical procedure and the consequent changes in food
      ingestion and digestion.

PMID- 19164565
TI  - A network biology approach to aging in yeast.
AB  - In this study, a reverse-engineering strategy was used to infer and analyze the
      structure and function of an aging and glucose repressed gene regulatory network
      in the budding yeast Saccharomyces cerevisiae. The method uses transcriptional
      perturbations to model the functional interactions between genes as a system of
      first-order ordinary differential equations. The resulting network model
      correctly identified the known interactions of key regulators in a 10-gene
      network from the Snf1 signaling pathway, which is required for expression of
      glucose-repressed genes upon calorie restriction. The majority of interactions
      predicted by the network model were confirmed using promoter-reporter gene
      fusions in gene-deletion mutants and chromatin immunoprecipitation experiments,
      revealing a more complex network architecture than previously appreciated. The
      reverse-engineered network model also predicted an unexpected role for
      transcriptional regulation of the SNF1 gene by hexose kinase
      enzyme/transcriptional repressor Hxk2, Mediator subunit Med8, and transcriptional
      repressor Mig1. These interactions were validated experimentally and used to
      design new experiments demonstrating Snf1 and its transcriptional regulators Hxk2
      and Mig1 as modulators of chronological lifespan. This work demonstrates the
      value of using network inference methods to identify and characterize the
      regulators of complex phenotypes, such as aging.

PMID- 19164566
TI  - Bimodal modulation of the botulinum neurotoxin protein-conducting channel.
AB  - Clostridium botulinum neurotoxin (BoNT) is the causative agent of botulism, a
      neuroparalytic disease. We describe here a semisynthetic strategy to identify
      inhibitors based on toosendanin, a traditional Chinese medicine reported to
      protect from BoNT intoxication. Using a single molecule assay of BoNT serotypes A
      and E light chain (LC) translocation through the heavy chain (HC) channel in
      neurons, we discovered that toosendanin and its tetrahydrofuran analog
      selectively arrest the LC translocation step of intoxication with subnanomolar
      potency, and increase the unoccluded HC channel propensity to open with
      micromolar efficacy. The inhibitory profile on LC translocation is accurately
      recapitulated in 2 different BoNT intoxication assays, namely the mouse
      protection and the primary rat spinal cord cell assays. Toosendanin has an
      unprecedented dual mode of action on the protein-conducting channel acting as a
      cargo-dependent inhibitor of translocation and as cargo-free channel activator.
      These results imply that the bimodal modulation by toosendanin depends on the
      dynamic interactions between channel and cargo, highlighting their tight
      interplay during the progression of LC transit across endosomes.

PMID- 19164567
TI  - Chromatin assembly factors Asf1 and CAF-1 have overlapping roles in deactivating
      the DNA damage checkpoint when DNA repair is complete.
AB  - In response to a DNA double-strand break (DSB), chromatin is rapidly modified by
      the damage dependent checkpoint kinases. Also, disassembly of chromatin occurs at
      the break site. The damage-induced modification of chromatin structure is
      involved in the maintenance of the checkpoint. However, it has not been
      determined how chromatin is restored to its undamaged state when DSB repair is
      complete. Here, we show the involvement of two chromatin assembly factors (CAFs),
      Asf1 and CAF-1, in turning off the DNA damage checkpoint in budding yeast. DSB
      repair or formation of gamma-H2AX does not depend on either the CAF-1 protein,
      Cac1, or Asf1. Absence of these proteins does not impair the ability of cells to
      resume cell cycle progression in the presence of an unrepaired DSB (adaptation).
      However, recovery from cell cycle checkpoint arrest when the DSB is repaired by
      gene conversion is substantially defective in the absence of both CAF-1 and Asf1,
      whereas deleting CAC1 or ASF1 individually had little effect. We suggest that CAF
      1 and Asf1 function redundantly to deactivate the checkpoint by restoring
      chromatin structure on the completion of DSB repair.

PMID- 19164568
TI  - Mechanisms of Auger-induced chemistry derived from wave packet dynamics.
AB  - To understand how core ionization and subsequent Auger decay lead to bond
      breaking in large systems, we simulate the wave packet dynamics of electrons in
      the hydrogenated diamond nanoparticle C(197)H(112). We find that surface core
      ionizations cause emission of carbon fragments and protons through a direct Auger
      mechanism, whereas deeper core ionizations cause hydrides to be emitted from the
      surface via remote heating, consistent with results from photon-stimulated
      desorption experiments [Hoffman A, Laikhtman A, (2006) J Phys Condens Mater
      18:S1517-S1546]. This demonstrates that it is feasible to study the chemistry of
      highly excited large-scale systems using simulation and analysis tools comparable
      in simplicity to those used for classical molecular dynamics.

PMID- 19164569
TI  - Somatosensory function in speech perception.
AB  - Somatosensory signals from the facial skin and muscles of the vocal tract provide
      a rich source of sensory input in speech production. We show here that the
      somatosensory system is also involved in the perception of speech. We use a
      robotic device to create patterns of facial skin deformation that would normally
      accompany speech production. We find that when we stretch the facial skin while
      people listen to words, it alters the sounds they hear. The systematic perceptual
      variation we observe in conjunction with speech-like patterns of skin stretch
      indicates that somatosensory inputs affect the neural processing of speech sounds
      and shows the involvement of the somatosensory system in the perceptual
      processing in speech.

PMID- 19164570
TI  - RodZ, a component of the bacterial core morphogenic apparatus.
AB  - The molecular basis of bacterial cell morphogenesis remains largely an open
      question. Here we discover a morphogenic protein, RodZ, which is widely conserved
      across the bacterial kingdom. In Caulobacter crescentus, RodZ is essential for
      viability and is involved in all aspects of this organism's complex morphology.
      Depletion or over-production of RodZ results in grossly misshapen cells with
      stalk defects. RodZ exhibits a localization pattern during the cell cycle
      corresponding to sites of active peptidoglycan synthesis. The temporal transition
      of RodZ between patchy/helical and mid-cell localization mimics and depends on
      the actin-like MreB cytoskeleton. In Escherichia coli, an organism with a
      distinct mode of growth and MreB localization dynamics, RodZ follows MreB and
      retains its crucial role in cell morphogenesis, demonstrating conservation of
      function. Genomic analysis shows that RodZ represents an ancient function unique
      to bacteria. Multiple sequence alignment of 143 RodZ sequences from species
      across bacterial phyla identifies an N-terminal cytoplasmic domain with a helix
      turn-helix motif, a transmembrane sequence, and a previously unidentified,
      conserved periplasmic or extracellular C-terminal domain. Both the N- and C
      terminal domains are important for function, with the N-terminal domain
      containing localization determinants. This study uncovers a key missing player in
      the cytoskeleton-based growth machinery enabling heritable and defined cellular
      forms in bacteria.

PMID- 19164571
TI  - Capsule of Cryptococcus neoformans grows by enlargement of polysaccharide
      molecules.
AB  - The human pathogenic fungus Cryptococcus neoformans has a distinctive
      polysaccharide (PS) capsule that enlarges during infection. The capsule is
      essential for virulence, but the mechanism for capsular growth is unknown. In the
      present study, we used dynamic light scattering (LS) analysis of capsular PS and
      optical tweezers (OT) to explore the architecture of the capsule. Analysis of
      capsular PS from cells with small and large capsules by dynamic LS revealed a
      linear correlation between PS effective diameter and microscopic capsular
      diameter. This result implied that capsule growth was achieved by the addition of
      molecules with larger effective diameter, such that some molecules can span the
      entire diameter of the capsule. Measurement of polystyrene bead penetration of C.
      neoformans capsules by using OT techniques revealed that the outer regions were
      penetrable, but not the inner regions. Our results provide a mechanism for
      capsular enlargement based on the axial lengthening of PS molecules and suggest a
      model for the architecture of a eukaryotic microbial capsule.

PMID- 19164572
TI  - Msc1 links dynamic Swi6/HP1 binding to cell fate determination.
AB  - Eukaryotic genomes can be organized into distinct domains of heterochromatin or
      euchromatin. In the fission yeast Schizosaccharomyces pombe, assembly of
      heterochromatin at the silent mating-type region is critical for cell fate
      determination in the form of mating-type switching. Here, we report that the
      ubiquitin ligase, Msc1, is a critical factor required for proper cell fate
      determination in S. pombe. In the absence of Msc1, the in vivo mobility of Swi6
      at heterochromatic foci is compromised, and centromere heterochromatin becomes
      hyperenriched with the heterochromatin binding protein Swi6/HP1. However, at the
      mating-type locus, Swi6 recruitment is defective in the absence of Msc1.
      Therefore, Msc1 links maintaining dynamic heterochromatin with proper
      heterochromatin assembly and cell fate determination. These findings have
      implications for understanding mechanisms of differentiation in other organisms.

PMID- 19164573
TI  - Elevation increases in moth assemblages over 42 years on a tropical mountain.
AB  - Physiological research suggests that tropical insects are particularly sensitive
      to temperature, but information on their responses to climate change has been
      lacking-even though the majority of all terrestrial species are insects and their
      diversity is concentrated in the tropics. Here, we provide evidence that tropical
      insect species have already undertaken altitude increases, confirming the global
      reach of climate change impacts on biodiversity. In 2007, we repeated a
      historical altitudinal transect, originally carried out in 1965 on Mount Kinabalu
      in Borneo, sampling 6 moth assemblages between 1,885 and 3,675 m elevation. We
      estimate that the average altitudes of individuals of 102 montane moth species,
      in the family Geometridae, increased by a mean of 67 m over the 42 years. Our
      findings indicate that tropical species are likely to be as sensitive as
      temperate species to climate warming, and we urge ecologists to seek other
      historic tropical samples to carry out similar repeat surveys. These observed
      changes, in combination with the high diversity and thermal sensitivity of
      insects, suggest that large numbers of tropical insect species could be affected
      by climate warming. As the highest mountain in one of the most biodiverse regions
      of the world, Mount Kinabalu is a globally important refuge for terrestrial
      species that become restricted to high altitudes by climate warming.

PMID- 19164574
TI  - Intersubunit allosteric communication mediated by a conserved loop in the MCM
      helicase.
AB  - The minichromosome maintenance (MCM) helicase is the presumptive replicative
      helicase in archaea and eukaryotes. The archaeal homomultimeric MCM has a two
      tier structure. One tier contains the AAA+ motor domains of the proteins, and
      these are the minimal functional helicase domains. The second tier is formed by
      the N-terminal domains. These domains are not essential for MCM helicase activity
      but act to enhance the processivity of the helicase. We reveal that a conserved
      loop facilitates communication between processivity and motor tiers.
      Interestingly, this allostery seems to be mediated by interactions between,
      rather than within, individual protomers in the MCM ring.

PMID- 19164575
TI  - Targeted disruption of the Cl-/HCO3- exchanger Ae2 results in osteopetrosis in
      mice.
AB  - Osteoclasts are multinucleated bone-resorbing cells responsible for constant
      remodeling of bone tissue and for maintaining calcium homeostasis. The osteoclast
      creates an enclosed space, a lacuna, between their ruffled border membrane and
      the mineralized bone. They extrude H(+) and Cl(-) into these lacunae by the
      combined action of vesicular H(+)-ATPases and ClC-7 exchangers to dissolve the
      hydroxyapatite of bone matrix. Along with intracellular production of H(+) and
      HCO(3)(-) by carbonic anhydrase II, the H(+)-ATPases and ClC-7 exchangers seems
      prerequisite for bone resorption, because genetic disruption of either of these
      proteins leads to osteopetrosis. We aimed to complete the molecular model for
      lacunar acidification, hypothesizing that a HCO(3)(-) extruding and Cl(-) loading
      anion exchange protein (Ae) would be necessary to sustain bone resorption. The Ae
      proteins can provide both intracellular pH neutrality and serve as cellular entry
      mechanism for Cl(-) during bone resorption. Immunohistochemistry revealed that
      Ae2 is exclusively expressed at the contra-lacunar plasma membrane domain of
      mouse osteoclast. Severe osteopetrosis was encountered in Ae2 knockout (Ae2-/-)
      mice where the skeletal development was impaired with a higher diffuse radio
      density on x-ray examination and the bone marrow cavity was occupied by irregular
      bone speculae. Furthermore, osteoclasts in Ae2-/- mice were dramatically enlarged
      and fail to form the normal ruffled border facing the lacunae. Thus, Ae2 is
      likely to be an essential component of the bone resorption mechanism in
      osteoclasts.

PMID- 19164576
TI  - Female promiscuity promotes the evolution of faster sperm in cichlid fishes.
AB  - Sperm competition, the contest among ejaculates from rival males to fertilize ova
      of a female, is a common and powerful evolutionary force influencing ejaculate
      traits. During competitive interactions between ejaculates, longer and faster
      spermatozoa are expected to have an edge; however, to date, there has been mixed
      support for this key prediction from sperm competition theory. Here, we use the
      spectacular radiation of cichlid fishes from Lake Tanganyika to examine sperm
      characteristics in 29 closely related species. We provide phylogenetically robust
      evidence that species experiencing greater levels of sperm competition have
      faster-swimming sperm. We also show that sperm competition selects for increases
      in the number, size, and longevity of spermatozoa in the ejaculate of a male,
      and, contrary to expectations from theory, we find no evidence of trade-offs
      among sperm traits in an interspecific analysis. Also, sperm swimming speed is
      positively correlated with sperm length among, but not within, species. These
      different responses to sperm competition at intra- and interspecific levels
      provide a simple, powerful explanation for equivocal results from previous
      studies. Using phylogenetic analyses, we also reconstructed the probable
      evolutionary route of trait evolution in this taxon, and show that, in response
      to increases in the magnitude of sperm competition, the evolution of sperm traits
      in this clade began with the evolution of faster (thus, more competitive) sperm.

PMID- 19164577
TI  - Hyperactivity and hyperconnectivity of the default network in schizophrenia and
      in first-degree relatives of persons with schizophrenia.
AB  - We examined the status of the neural network mediating the default mode of brain
      function, which typically exhibits greater activation during rest than during
      task, in patients in the early phase of schizophrenia and in young first-degree
      relatives of persons with schizophrenia. During functional MRI, patients,
      relatives, and controls alternated between rest and performance of working memory
      (WM) tasks. As expected, controls exhibited task-related suppression of
      activation in the default network, including medial prefrontal cortex (MPFC) and
      posterior cingulate cortex/precuneus. Patients and relatives exhibited
      significantly reduced task-related suppression in MPFC, and these reductions
      remained after controlling for performance. Increased task-related MPFC
      suppression correlated with better WM performance in patients and relatives and
      with less psychopathology in all 3 groups. For WM task performance, patients and
      relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC)
      than controls. During rest and task, patients and relatives exhibited abnormally
      high functional connectivity within the default network. The magnitudes of
      default network connectivity during rest and task correlated with psychopathology
      in the patients. Further, during both rest and task, patients exhibited reduced
      anticorrelations between MPFC and DLPFC, a region that was hyperactivated by
      patients and relatives during WM performance. Among patients, the magnitude of
      MPFC task suppression negatively correlated with default connectivity, suggesting
      an association between the hyperactivation and hyperconnectivity in
      schizophrenia. Hyperactivation (reduced task-related suppression) of default
      regions and hyperconnectivity of the default network may contribute to
      disturbances of thought in schizophrenia and risk for the illness.

PMID- 19164578
TI  - Periodic reversal of direction allows Myxobacteria to swarm.
AB  - Many bacteria can rapidly traverse surfaces from which they are extracting
      nutrient for growth. They generate flat, spreading colonies, called swarms
      because they resemble swarms of insects. We seek to understand how members of any
      dense swarm spread efficiently while being able to perceive and interfere
      minimally with the motion of others. To this end, we investigate swarms of the
      myxobacterium, Myxococcus xanthus. Individual M. xanthus cells are elongated;
      they always move in the direction of their long axis; and they are in constant
      motion, repeatedly touching each other. Remarkably, they regularly reverse their
      gliding directions. We have constructed a detailed cell- and behavior-based
      computational model of M. xanthus swarming that allows the organization of cells
      to be computed. By using the model, we are able to show that reversals of gliding
      direction are essential for swarming and that reversals increase the outflow of
      cells across the edge of the swarm. Cells at the swarm edge gain maximum exposure
      to nutrient and oxygen. We also find that the reversal period predicted to
      maximize the outflow of cells is the same (within the errors of measurement) as
      the period observed in experiments with normal M. xanthus cells. This coincidence
      suggests that the circuit regulating reversals evolved to its current sensitivity
      under selection for growth achieved by swarming. Finally, we observe that, with
      time, reversals increase the cell alignment, and generate clusters of parallel
      cells.

PMID- 19164579
TI  - Altered temporal correlations in parietal alpha and prefrontal theta oscillations
      in early-stage Alzheimer disease.
AB  - Encoding and retention of information in memory are associated with a sustained
      increase in the amplitude of neuronal oscillations for up to several seconds. We
      reasoned that coordination of oscillatory activity over time might be important
      for memory and, therefore, that the amplitude modulation of oscillations may be
      abnormal in Alzheimer disease (AD). To test this hypothesis, we measured
      magnetoencephalography (MEG) during eyes-closed rest in 19 patients diagnosed
      with early-stage AD and 16 age-matched control subjects and characterized the
      autocorrelation structure of ongoing oscillations using detrended fluctuation
      analysis and an analysis of the life- and waiting-time statistics of oscillation
      bursts. We found that Alzheimer's patients had a strongly reduced incidence of
      alpha-band oscillation bursts with long life- or waiting-times (< 1 s) over
      temporo-parietal regions and markedly weaker autocorrelations on long time scales
      (1-25 seconds). Interestingly, the life- and waiting-times of theta oscillations
      over medial prefrontal regions were greatly increased. Whereas both temporo
      parietal alpha and medial prefrontal theta oscillations are associated with
      retrieval and retention of information, metabolic and structural deficits in
      early-stage AD are observed primarily in temporo-parietal areas, suggesting that
      the enhanced oscillations in medial prefrontal cortex reflect a compensatory
      mechanism. Together, our results suggest that amplitude modulation of neuronal
      oscillations is important for cognition and that indices of amplitude dynamics of
      oscillations may prove useful as neuroimaging biomarkers of early-stage AD.

PMID- 19164580
TI  - Polymicrobial interactions stimulate resistance to host innate immunity through
      metabolite perception.
AB  - Bacteria in the human oral cavity often grow in an attached multispecies biofilm
      community. Members of this community display defined interactions that have an
      impact on the physiology of the individual and the group. Here, we show that
      during coculture growth with streptococci, the oral pathogen Aggregatibacter
      actinomycetemcomitans displays enhanced resistance to killing by host innate
      immunity. The mechanism of resistance involves sensing of the streptococcal
      metabolite hydrogen peroxide by A. actinomycetemcomitans, which stimulates a
      genetic program resulting in enhanced expression of the complement resistance
      protein ApiA. The oxidative stress response regulator OxyR mediates induction of
      apiA transcription, and this induction is required for coculture resistance to
      killing by human serum. These findings provide evidence that interaction between
      community members mediates prokaryotic resistance to host innate immunity and
      reinforce the need to understand how polymicrobial growth affects interaction
      with the host immune system.

PMID- 19164581
TI  - The coactivator CRTC1 promotes cell proliferation and transformation via AP-1.
AB  - Regulation of gene expression in response to mitogenic stimuli is a critical
      aspect underlying many forms of human cancers. The AP-1 complex mediates the
      transcriptional response to mitogens, and its deregulation causes developmental
      defects and tumors. We report that the coactivator CRTC1 cyclic AMP response
      element-binding protein (CREB)-regulated transcription coactivator 1 is a potent
      and indispensable modulator of AP-1 function. After exposure of cells to the AP-1
      agonist 12-O-tetradecanoylphorbol-13-acetate (TPA), CRTC1 is recruited to AP-1
      target gene promoters and associates with c-Jun and c-Fos to activate
      transcription. CRTC1 consistently synergizes with the proto-oncogene c-Jun to
      promote cellular growth, whereas AP-1-dependent proliferation is abrogated in
      CRTC1-deficient cells. Remarkably, we demonstrate that CRTC1-Maml2 oncoprotein,
      which causes mucoepidermoid carcinomas, binds and activates both c-Jun and c-Fos.
      Consequently, ablation of AP-1 function disrupts the cellular transformation and
      proliferation mediated by this oncogene. Together, these data illustrate a novel
      mechanism required to couple mitogenic signals to the AP-1 gene regulatory
      program.

PMID- 19164582
TI  - A matrix convexity approach to some celebrated quantum inequalities.
AB  - Some of the important inequalities associated with quantum entropy are immediate
      algebraic consequences of the Hansen-Pedersen-Jensen inequalities. A general
      argument is given using matrix perspectives of operator convex functions. A
      matrix analogue of Marechal's extended perspectives provides additional
      inequalities, including a p + q < or = 1 result of Lieb.

PMID- 19164583
TI  - GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in
      cellular and rodent models of stroke and Parkinsonism.
AB  - Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic peptide secreted
      from the gastrointestinal tract in response to food intake. It enhances
      pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion,
      and lowers blood glucose and food intake in patients with type 2 diabetes
      mellitus (T2DM). A long-acting GLP-1 receptor (GLP-1R) agonist, exendin-4 (Ex-4),
      is the first of this new class of antihyperglycemia drugs approved to treat T2DM.
      GLP-1Rs are coupled to the cAMP second messenger pathway and, along with
      pancreatic cells, are expressed within the nervous system of rodents and humans,
      where receptor activation elicits neurotrophic actions. We detected GLP-1R mRNA
      expression in both cultured embryonic primary cerebral cortical and ventral
      mesencephalic (dopaminergic) neurons. These cells are vulnerable to hypoxia- and
      6-hydroxydopamine-induced cell death, respectively. We found that GLP-1 and Ex-4
      conferred protection in these cells, but not in cells from Glp1r knockout (-/-)
      mice. Administration of Ex-4 reduced brain damage and improved functional outcome
      in a transient middle cerebral artery occlusion stroke model. Ex-4 treatment also
      protected dopaminergic neurons against degeneration, preserved dopamine levels,
      and improved motor function in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) mouse model of Parkinson's disease (PD). Our findings demonstrate that Ex
      4 can protect neurons against metabolic and oxidative insults, and they provide
      preclinical support for the therapeutic potential for Ex-4 in the treatment of
      stroke and PD.

PMID- 19164584
TI  - Learning-related postburst afterhyperpolarization reduction in CA1 pyramidal
      neurons is mediated by protein kinase A.
AB  - Learning-related reductions of the postburst afterhyperpolarization (AHP) in
      hippocampal pyramidal neurons have been shown ex vivo, after trace eyeblink
      conditioning. The AHP is also reduced by many neuromodulators, such as
      norepinephrine, via activation of protein kinases. Trace eyeblink conditioning,
      like other hippocampus-dependent tasks, relies on protein synthesis for
      consolidating the learned memory. Protein kinase A (PKA) has been shown to be a
      key contributor for protein synthesis via the cAMP-response element-binding
      pathway. Here, we have explored a potential involvement of PKA and protein kinase
      C (PKC) in maintaining the learning-related postburst AHP reduction observed in
      CA1 pyramidal neurons. Bath application of isoproterenol (1 muM), a beta
      adrenergic agonist that activates PKA, significantly reduced the AHP in CA1
      neurons from control animals, but not from rats that learned. This occlusion
      suggests that PKA activity is involved in maintaining the AHP reduction measured
      ex vivo after successful learning. In contrast, bath application of the PKC
      activator, (-) indolactam V (0.2 muM), significantly reduced the AHP in CA1
      neurons from both control and trained rats, indicating that PKC activity is not
      involved in maintaining the AHP reduction at this point after learning.

PMID- 19164585
TI  - Functional organization of the yeast proteome by a yeast interactome map.
AB  - It is hoped that comprehensive mapping of protein physical interactions will
      facilitate insights regarding both fundamental cell biology processes and the
      pathology of diseases. To fulfill this hope, good solutions to 2 issues will be
      essential: (i) how to obtain reliable interaction data in a high-throughput
      setting and (ii) how to structure interaction data in a meaningful form, amenable
      to and valuable for further biological research. In this article, we structure an
      interactome in terms of predicted permanent protein complexes and predicted
      transient, nongeneric interactions between these complexes. The interactome is
      generated by means of an associated computational algorithm, from raw high
      throughput affinity purification/mass spectrometric interaction data. We apply
      our technique to the construction of an interactome for Saccharomyces cerevisiae,
      showing that it yields reliability typical of low-throughput experiments from
      high-throughput data. We discuss biological insights raised by this interactome
      including, via homology, a few related to human disease.

PMID- 19164586
TI  - Src-dependent repression of ARF6 is required to maintain podosome-rich sealing
      zones in bone-digesting osteoclasts.
AB  - Bone digestion occurs when osteoclasts adhere onto bone surfaces and polarize to
      form acidic, hydrolase-rich resorption lacunae. For this process, they condense
      their actin-rich podosomes in tight belts to establish sealing zones, which
      segregate their basal membranes from those facing resorption lacunae. This
      polarization process remains poorly understood. Here, we combined quantitative
      proteomics and gene silencing to identify new substrates of the Src tyrosine
      kinase, a key regulator of osteoclast function. We now report that a depletion of
      the ARF GTPase-activating protein GIT2, which localizes to sealing zones upon Src
      phosphorylation, or a lack of GTP hydrolysis on ARF6 impairs sealing zone
      formation and polarized membrane traffic. Surprisingly, the Rho guanine
      nucleotide exchange factors alpha and beta PIX, which usually coordinate ARF and
      Rho signaling, were found to be dispensable. We conclude that the Src-dependent
      localization of GIT2 is essential for down-regulating ARF6 activity at sealing
      zones, and thus for maintaining osteoclast polarity.

PMID- 19164587
TI  - Evidence of gender differences in the ability to inhibit brain activation
      elicited by food stimulation.
AB  - Although impaired inhibitory control is linked to a broad spectrum of health
      problems, including obesity, the brain mechanism(s) underlying voluntary control
      of hunger are not well understood. We assessed the brain circuits involved in
      voluntary inhibition of hunger during food stimulation in 23 fasted men and women
      using PET and 2-deoxy-2[(18)F]fluoro-D-glucose ((18)FDG). In men, but not in
      women, food stimulation with inhibition significantly decreased activation in
      amygdala, hippocampus, insula, orbitofrontal cortex, and striatum, which are
      regions involved in emotional regulation, conditioning, and motivation. The
      suppressed activation of the orbitofrontal cortex with inhibition in men was
      associated with decreases in self-reports of hunger, which corroborates the
      involvement of this region in processing the conscious awareness of the drive to
      eat. This finding suggests a mechanism by which cognitive inhibition decreases
      the desire for food and implicates lower ability to suppress hunger in women as a
      contributing factor to gender differences in obesity.

PMID- 19164588
TI  - Restrictions on biological adaptation in language evolution.
AB  - Language acquisition and processing are governed by genetic constraints. A
      crucial unresolved question is how far these genetic constraints have coevolved
      with language, perhaps resulting in a highly specialized and species-specific
      language "module," and how much language acquisition and processing redeploy
      preexisting cognitive machinery. In the present work, we explored the
      circumstances under which genes encoding language-specific properties could have
      coevolved with language itself. We present a theoretical model, implemented in
      computer simulations, of key aspects of the interaction of genes and language.
      Our results show that genes for language could have coevolved only with highly
      stable aspects of the linguistic environment; a rapidly changing linguistic
      environment does not provide a stable target for natural selection. Thus, a
      biological endowment could not coevolve with properties of language that began as
      learned cultural conventions, because cultural conventions change much more
      rapidly than genes. We argue that this rules out the possibility that arbitrary
      properties of language, including abstract syntactic principles governing phrase
      structure, case marking, and agreement, have been built into a "language module"
      by natural selection. The genetic basis of human language acquisition and
      processing did not coevolve with language, but primarily predates the emergence
      of language. As suggested by Darwin, the fit between language and its underlying
      mechanisms arose because language has evolved to fit the human brain, rather than
      the reverse.

PMID- 19164589
TI  - Noninvasive cortical stimulation enhances motor skill acquisition over multiple
      days through an effect on consolidation.
AB  - Motor skills can take weeks to months to acquire and can diminish over time in
      the absence of continued practice. Thus, strategies that enhance skill
      acquisition or retention are of great scientific and practical interest. Here we
      investigated the effect of noninvasive cortical stimulation on the extended time
      course of learning a novel and challenging motor skill task. A skill measure was
      chosen to reflect shifts in the task's speed-accuracy tradeoff function (SAF),
      which prevented us from falsely interpreting variations in position along an
      unchanged SAF as a change in skill. Subjects practiced over 5 consecutive days
      while receiving transcranial direct current stimulation (tDCS) over the primary
      motor cortex (M1). Using the skill measure, we assessed the impact of anodal
      (relative to sham) tDCS on both within-day (online) and between-day (offline)
      effects and on the rate of forgetting during a 3-month follow-up (long-term
      retention). There was greater total (online plus offline) skill acquisition with
      anodal tDCS compared to sham, which was mediated through a selective enhancement
      of offline effects. Anodal tDCS did not change the rate of forgetting relative to
      sham across the 3-month follow-up period, and consequently the skill measure
      remained greater with anodal tDCS at 3 months. This prolonged enhancement may
      hold promise for the rehabilitation of brain injury. Furthermore, these findings
      support the existence of a consolidation mechanism, susceptible to anodal tDCS,
      which contributes to offline effects but not to online effects or long-term
      retention.

PMID- 19164590
TI  - Sum rules and determination of exciton coupling using absorption and circular
      dichroism spectra of biological polymers.
AB  - Optical spectra of biological polymers contain important information about their
      structure and function in living organisms. This information can be accessed by
      extracting an optical interaction of monomers, i.e., their exciton coupling, from
      experimental data. This coupling is sensitive to molecular structure, geometry,
      and conformation and can be used to characterize them. However, the accurate
      determination of exciton coupling in important biological molecules is difficult
      because inhomogeneous broadening smears out the monomer interaction. We suggest a
      way to overcome this problem by applying exact sum rules. These sum rules are
      derived by establishing a straightforward relationship between integral
      characteristics of absorption and circular dicroism spectra, and exciton
      coupling. Exciton coupling between AT pairs in native DNA conformation is
      estimated by applying these sum rules to DNA hairpin optical spectra as V(0)
      approximately 0.035 eV in agreement with the earlier numerical calculations.

PMID- 19164591
TI  - Selective targeting of perivascular macrophages for clearance of beta-amyloid in
      cerebral amyloid angiopathy.
AB  - Cerebral amyloid angiopathy (CAA), the deposition of beta-amyloid (Abeta)
      peptides in leptomeningeal and cortical blood vessels, affects the majority of
      patients with Alzheimer's disease (AD). Evidence suggests that vascular amyloid
      deposits may result from impaired clearance of neuronal Abeta along perivascular
      spaces. We investigated the role of perivascular macrophages in regulating CAA
      severity in the TgCRND8 mouse model of AD. Depletion of perivascular macrophages
      significantly increased the number of thioflavin S-positive cortical blood
      vessels. ELISA confirmed that this increase was underscored by elevations in
      total vascular Abeta(42) levels. Conversely, stimulation of perivascular
      macrophage turnover reduced cerebral CAA load, an effect that was not mediated
      through clearance by microglia or astrocytes. These results highlight a function
      for the physiological role of perivascular macrophages in the regulation of CAA
      and suggest that selective targeting of perivascular macrophage activation might
      constitute a therapeutic strategy to clear vascular amyloid.

PMID- 19164592
TI  - A synthesized pheromone induces upstream movement in female sea lamprey and
      summons them into traps.
AB  - Female insect pheromone blends induce robust tracking responses in males and
      direct them into traps. In vertebrates, pheromones that induce strong and precise
      tracking responses in natural habitats have rarely been described. Here, we show
      in the sea lamprey (Petromyzon marinus), a vertebrate invader of the Laurential
      Great Lakes, that a synthesized component of the male mating pheromone, 7alpha,
      12alpha, 24-trihydroxy-5alpha-cholan-3-one 24-sulfate (3kPZS), when released into
      a stream to reach concentrations of 10(-14), 10(-13), 10(-12), 10(-11), or 10(
      10) M, triggers robust upstream movement in ovulated females drawing
      approximately 50% into baited traps. Experiments conducted in diverse stream
      segments demonstrate the level of behavioral response was not affected by habitat
      conditions and is effective over hundreds of meters. 3kPZS is equally effective
      at luring ovulated females as the whole pheromone blend released by males between
      10(-14) and 10(-11) M. 3kPZS diverts ovulated females away from and disrupts
      orientation to male washings when applied at concentrations higher than washings.
      Indeed, a single pheromone compound is able to redirect female sea lampreys away
      from a natural pheromone source and lure them into traps, which should be more
      effective than targeting males when applied in population control. Our findings
      may spur the discovery of other potent and environmentally benign agents to
      combat biological invasion, a process accelerated by globalization, exacerbated
      by climate change, and costing the global economy US$ 1.4 trillion of damage
      annually.

PMID- 19164593
TI  - Image-guided, noninvasive, spatiotemporal control of gene expression.
AB  - Spatiotemporal control of transgene expression is of paramount importance in gene
      therapy. Here, we demonstrate the use of magnetic resonance temperature imaging
      (MRI)-guided, high-intensity focused ultrasound (HIFU) in combination with a heat
      inducible promoter [heat shock protein 70 (HSP70)] for the in vivo spatiotemporal
      control of transgene activation. Local gene activation induced by moderate
      hyperthermia in a transgenic mouse expressing luciferase under the control of the
      HSP70 promoter showed a high similarity between the local temperature
      distribution in vivo and the region emitting light. Modulation of gene expression
      is possible by changing temperature, duration, and location of regional heating.
      Mild heating protocols (2 min at 43 degrees C) causing no tissue damage were
      sufficient for significant gene activation. The HSP70 promoter was shown to be
      induced by the local temperature increase and not by the mechanical effects of
      ultrasound. Therefore, the combination of MRI-guided HIFU heating and transgenes
      under control of heat-inducible HSP promoter provides a direct, noninvasive,
      spatial control of gene expression via local hyperthermia.

PMID- 19164594
TI  - An essential role for Radar (Gdf6a) in inducing dorsal fate in the zebrafish
      retina.
AB  - Retinal ganglion cells form orderly topographic connections with the tectum,
      establishing a continuous neural representation of visual space. Mapping along
      the dorsal-ventral axis requires interactions between EphB and ephrin-B cell
      surface molecules expressed as countergradients in both retina and tectum. We
      have discovered that the diffusible TGFss-related factor Radar (Gdf6a) is
      necessary and sufficient for activation of dorsal markers, such as Bmp4, Tbx5,
      Tbx2b, and Ephrin-B2, and suppression of the ventral marker Vax2 in the zebrafish
      retina. Radar mutant axons innervate only the dorsal half of the tectum, where
      they form a compressed retinotectal map. Wild-type cells transplanted into the
      dorsal retina are able to rescue the dorsal identity of nearby mutant cells.
      Moreover, Radar overexpression "dorsalizes" retinal ganglion cell identity in the
      ventral retina. We conclude that Radar is near the top of a signaling cascade
      that establishes dorsal-ventral positional information in the retina and controls
      the formation of the retinotectal map.

PMID- 19164595
TI  - The near-infrared nitric oxide nightglow in the upper atmosphere of Venus.
AB  - The v' = 0 progressions of the C --> X and A --> X band systems of nitric oxide
      dominate the middle-UV spectrum of the night-time upper atmospheres of the Earth,
      Mars, and Venus. The C(0) --> A(0)+h nu radiative transition at 1.224 mum, the
      only channel effectively populating the A(0) level, must therefore occur also.
      There have been, however, no reported detections of the C(0) --> A(0) band in the
      atmospheres of these or any other planets. We analyzed all available near
      infrared limb observations of the dark-side atmosphere of Venus by the Visible
      and Infrared Thermal Imaging Spectrometer (VIRTIS) instrument on the Venus
      Express spacecraft and found 2 unambiguous detections of this band at equatorial
      latitudes that seem to be associated with episodic events of highly enhanced
      nightglow emission. The discovery of the C(0) --> A(0) band means observations in
      the 1.2-1.3 microm region, which also contains the a(0) --> X(0) emission band of
      molecular oxygen, can provide a wealth of information on the high-altitude
      chemistry and dynamics of the Venusian atmosphere.

PMID- 19164596
TI  - Antigen mRNA-transfected, allogeneic fibroblasts loaded with NKT-cell ligand
      confer antitumor immunity.
AB  - The maturation of dendritic cells (DCs) in situ by danger signals plays a central
      role in linking innate and adaptive immunity. We previously demonstrated that the
      activation of invariant natural killer T (iNKT) cells by administration of alpha
      galactosylceramide (alpha-GalCer)-loaded tumor cells can act as a cellular
      adjuvant through the DC maturation. In the current study, we used allogeneic
      fibroblasts loaded with alpha-GalCer and transfected with antigen-encoding mRNA,
      thus combining the adjuvant effects of iNKT-cell activation with delivery of
      antigen to DCs in vivo. We found that these cells produce antigen protein and
      activate NK and iNKT cells. When injected into major histocompatibility complex
      (MHC)-mismatched mice, they elicited antigen-specific T-cell responses and
      provided tumor protection, suggesting that these immune responses depend on host
      DCs. In addition, antigen-expressing fibroblasts loaded with alpha-GalCer lead to
      a more potent T-cell response than those expressing NK cell ligands. Thus,
      glycolipid-loaded, mRNA-transfected allogeneic fibroblasts act as cellular
      vectors to provide iNKT-cell activation, leading to DC maturation and T-cell
      immunity. By harnessing the innate immune system and generating an adaptive
      immune response to a variety of antigens, this unique tool could prove clinically
      beneficial in the development of immunotherapies against malignant and infectious
      diseases.

PMID- 19164597
TI  - Inhibition of activation-induced death of dendritic cells and enhancement of
      vaccine efficacy via blockade of MINOR.
AB  - Activation of dendritic cells (DCs) leads to cell maturation, which is
      accompanied by a regulated pattern of gene expression changes. Two significant
      and contradictory consequences of DC activation are that, although activation is
      necessary for maximal T-cell stimulation, it also leads to the initiation of gene
      expression that results ultimately in cell death. We have identified a gene,
      MINOR (mitogen-inducible nuclear orphan receptor), that becomes highly up
      regulated on activation and whose expression leads to apoptosis in mature DCs.
      MINOR is a member of the Nur77 family of nuclear orphan receptors, which includes
      Nur77 and Nurr1. Although Nur77 and Nurr1 are expressed in macrophages and DCs,
      their expression levels do not change on DC activation. We thus tested the
      hypothesis that induction of MINOR would lead to an activation-induced cell death
      in DCs and that its inhibition would increase the lifespan of DCs and improve
      their vaccine efficacy. To block natural expression of MINOR by DCs, we generated
      a lentiviral vector that expresses a small interfering RNA. Our results indicate
      that blockade of MINOR expression dramatically decreases apoptosis in DCs and
      suggest that this approach may be a novel means to improve the potency of ex vivo
      generated DC vaccines.

PMID- 19164598
TI  - Impaired activation of platelets lacking protein kinase C-theta isoform.
AB  - Protein kinase C (PKC) isoforms have been implicated in several platelet
      functional responses, but the contribution of individual isoforms has not been
      thoroughly evaluated. Novel PKC isoform PKC-theta is activated by glycoprotein VI
      (GPVI) and protease-activated receptor (PAR) agonists, but not by adenosine
      diphosphate. In human platelets, PKC-theta-selective antagonistic (RACK; receptor
      for activated C kinase) peptide significantly inhibited GPVI and PAR-induced
      aggregation, dense and alpha-granule secretion at low agonist concentrations.
      Consistently, in murine platelets lacking PKC-theta, platelet aggregation and
      secretion were also impaired. PKC-mediated phosphorylation of tSNARE protein
      syntaxin-4 was strongly reduced in human platelets pretreated with PKC-theta RACK
      peptide, which may contribute to the lower levels of granule secretion when PKC
      theta function is lost. Furthermore, the level of JON/A binding to activated
      alpha(IIb)beta(3) receptor was also significantly decreased in PKC-theta(-/-)
      mice compared with wild-type littermates. PKC-theta(-/-) murine platelets showed
      significantly lower agonist-induced thromboxane A(2) (TXA(2)) release through
      reduced extracellular signal-regulated kinase phosphorylation. Finally, PKC
      theta(-/-) mice displayed unstable thrombus formation and prolonged arterial
      occlusion in the FeCl(3) in vivo thrombosis model compared with wild-type mice.
      In conclusion, PKC-theta isoform plays a significant role in platelet functional
      responses downstream of PAR and GPVI receptors.

PMID- 19164599
TI  - Gene expression profile of the third pharyngeal pouch reveals role of mesenchymal
      MafB in embryonic thymus development.
AB  - The thymus provides a microenvironment that induces the differentiation of T
      progenitor cells into functional T cells and that establishes a diverse yet self
      tolerant T-cell repertoire. However, the mechanisms that lead to the development
      of the thymus are incompletely understood. We report herein the results of
      screening for genes that are expressed in the third pharyngeal pouch, which
      contains thymic primordium. Polymerase chain reaction (PCR)-based cDNA
      subtraction screening for genes expressed in microdissected tissues of the third
      pharyngeal pouch rather than the second pharyngeal arch yielded one transcription
      factor, MafB, which was predominantly expressed in CD45(-)IA(-)PDGFRalpha(+)
      mesenchymal cells and was detectable even in the third pharyngeal pouch of FoxN1
      deficient nude mice. Interestingly, the number of CD45(+) cells that initially
      accumulated in the embryonic thymus was significantly decreased in MafB-deficient
      mice. Alterations of gene expression in the embryonic thymi of MafB-deficient
      mice included the reduced expression of Wnt3 and BMP4 in mesenchymal cells and of
      CCL21 and CCL25 in epithelial cells. These results suggest that MafB expressed in
      third pharyngeal pouch mesenchymal cells critically regulates lymphocyte
      accumulation in the embryonic thymus.

PMID- 19164600
TI  - A novel in vivo siRNA delivery system specifically targeting dendritic cells and
      silencing CD40 genes for immunomodulation.
AB  - Translation of small interfering RNA (siRNA)-based approaches into practical
      therapeutics is limited because of lack of an effective and cell-specific
      delivery system. Herein, we present a new method of selectively delivering siRNA
      to dendritic cells (DCs) in vivo using CD40 siRNA-containing immunoliposomes
      (siILs) that were decorated with DC-specific DEC-205 mAb. Administration of CD40
      siILs resulted in DC-specific cell targeting in vitro and in vivo. On treatment
      with CD40 siILs, the expression of CD40 in DCs, as well allostimulatory activity
      was inhibited. In vivo administration resulted in selective siRNA uptake into
      immune organs and functional immune modulation as assessed using a model antigen.
      In conclusion, this is the first demonstration of DC-specific siRNA delivery and
      gene silencing in vivo, which highlights the potential of DC-mediated immune
      modulation and the feasibility of siRNA-based clinical therapy.

PMID- 19164601
TI  - The proteasome load versus capacity balance determines apoptotic sensitivity of
      multiple myeloma cells to proteasome inhibition.
AB  - Proteasome inhibitors (PIs) are effective against multiple myeloma (MM), but the
      mechanisms of action and bases of individual susceptibility remain unclear.
      Recent work linked PI sensitivity to protein synthesis and proteasome activity,
      raising the question whether different levels of proteasome expression and
      workload underlie PI sensitivity in MM cells (MMCs). Exploiting human MM lines
      characterized by differential PI sensitivity, we report that highly sensitive
      MMCs express lower proteasome levels and higher proteasomal workload than
      relatively PI-resistant MMCs, resulting in the accumulation of polyubiquitinated
      proteins at the expense of free ubiquitin (proteasome stress). Manipulating
      proteasome expression or workload alters apoptotic sensitivity to PI,
      demonstrating a cause-effect relationship between proteasome stress and apoptotic
      responses in MMCs. Intracellular immunostaining in primary, patient-derived MMCs
      reveals that polyubiquitinated proteins hallmark neoplastic plasma cells, in
      positive correlation with immunoglobulin (Ig) content, both intra- and
      interpatient. Moreover, overall proteasome activity of primary MMCs inversely
      correlates with apoptotic sensitivity to PI. Altogether, our data indicate that
      the balance between proteasome workload and degradative capacity represents a
      critical determinant of apoptotic sensitivity of MMCs to PI, potentially
      providing a framework for identifying indicators of responsiveness and designing
      novel combination therapies.

PMID- 19164602
TI  - Loss of caveolin-3 induces a lactogenic microenvironment that is protective
      against mammary tumor formation.
AB  - Here, we show that functional loss of a single gene is sufficient to confer
      constitutive milk protein production and protection against mammary tumor
      formation. Caveolin-3 (Cav-3), a muscle-specific caveolin-related gene, is highly
      expressed in muscle cells. We demonstrate that Cav-3 is also expressed in
      myoepithelial cells within the mammary gland. To determine whether genetic
      ablation of Cav-3 expression affects adult mammary gland development, we studied
      the phenotype(s) of Cav-3(-/-)-null mice. Interestingly, Cav-3(-/-) virgin
      mammary glands developed lobulo-alveolar hyperplasia, akin to the changes
      normally observed during pregnancy and lactation. Genome-wide expression
      profiling revealed up-regulation of gene transcripts associated with
      pregnancy/lactation, mammary stem cells, and human breast cancers, consistent
      with a constitutive lactogenic phenotype. Expression levels of three key
      transcriptional regulators of lactation, namely Elf5, Stat5a, and c-Myc, were
      also significantly elevated. Experiments with pregnant mice directly showed that
      Cav-3(-/-) mice underwent precocious lactation. Finally, using orthotopic tumor
      cell implantation, we demonstrated that virgin Cav-3(-/-) mice were dramatically
      protected against mammary tumor formation. Thus, Cav-3(-/-) mice are a novel
      preclinical model to study the protective effects of a lactogenic
      microenvironment on mammary tumor onset and progression. Our current studies have
      broad implications for using the lactogenic microenvironment as a paradigm to
      discover new therapies for the prevention and/or treatment of human breast
      cancers.

PMID- 19164603
TI  - Caveolin-1 expression determines the route of neutrophil extravasation through
      skin microvasculature.
AB  - Interleukin-8 plays a key role in the acute inflammatory response by mediating
      recruitment of neutrophils through vessel walls into affected tissues. During
      this process, molecular signals guide circulating blood neutrophils to target
      specific vessels for extravasation and to migrate through such vessels via
      particular routes. Our results show that levels of endothelial caveolin-1, the
      protein responsible for the induction of the membrane domains known as caveolae,
      are critical to each of these processes. We demonstrate that, in response to the
      intradermal injection of interleukin-8, neutrophils are preferentially recruited
      to a unique subset of venules that express high levels of intercellular adhesion
      molecule-1 and low levels of caveolin-1. Our results show that neutrophils
      traverse human dermal microvascular endothelial cells using one of two pathways:
      a transcellular route directly through the cell or a paracellular route through
      cellular junctions. Caveolin-1 expression appears to favor the transcellular path
      while down-regulation of caveolin-1 promotes the paracellular route.

PMID- 19164604
TI  - Learning from the missed opportunities for HIV testing.

PMID- 19164605
TI  - Commentary on "prevalence and risk factors for Chlamydia trachomatis infection
      among cross-border truck drivers in Hong Kong".

PMID- 19164606
TI  - Testing for HIV and sexually transmissible infections within a mainly online
      sample of gay men who engage in group sex.
AB  - INTRODUCTION: Group sex among gay men has been associated with other HIV risk
      behaviours. Gay men who engage in group sex may be at increased risk of infection
      with HIV and other sexually transmitted infections (STI). METHODS: The Three or
      More Study (TOMS) of group sex among gay men utilised an anonymous, self
      completed survey about participants' most recent occasion of group sex with other
      men and in-depth interviews with a small number of these survey participants. The
      436 men who reported having engaged in group sex within the previous month were
      included in these analyses. RESULTS: Among 436 men who engaged in group sex
      within the previous month, 32.5% reported unprotected anal intercourse (UAI) with
      non-regular, mostly HIV non-seroconcordant partners at this recent group sex
      encounter (GSE) and the majority reported other sex practices that are risk
      factors for STI other than HIV. Over one-third reported having been tested for
      HIV or other STI since their last GSE; those who had engaged in UAI at the GSE
      were more likely to have been tested (p = 0.008). Men who had a doctor with whom
      they were able to discuss their group sex activities had received a broader range
      of STI tests (p = 0.003). CONCLUSION: Sex practices that risk the transmission of
      STI were common within this high-risk sample, whereas awareness of risk and the
      need for testing was high but not universal. Frank discussion with doctors of
      patients' group sex behaviour also enhanced decisions about adequate testing. Gay
      men in group sex networks are an appropriate priority for sexual health
      screening.

PMID- 19164607
TI  - The integral piece of integration.

PMID- 19164609
TI  - Influence of preoperative feeding on the healing of colonic anastomoses in
      malnourished rats.
AB  - BACKGROUND: Malnutrition influences healing of gastrointestinal anastomoses. The
      authors hypothesize that colonic anastomotic healing is decreased by malnutrition
      and might be improved by preoperative feeding. METHODS: Eighty adult male Wistar
      rats were divided into 4 groups: (1) control rats 1 (C1), fed regular chow ad
      libitum for 21 days; (2) malnourished pair-fed rats (M), fed 50% of the food
      ingested by the control rats for 21 days; (3) preoperative nutrition rats (PRE),
      fed 50% of the average of the controls for 21 days and then fed preoperative
      nutrition with regular chow ad libitum for 1 week before the operation; and (4)
      control rats 2 (C2), fed regular chow ad libitum for 28 days. On days 21 (C1 and
      M) and 28 (PRE and C2), rats underwent 2 colonic transections and, subsequently,
      2 end-to-end anastomoses. Rats were killed on postoperative day 5. The
      anastomoses were resected for tensile strength and histological analysis.
      RESULTS: PRE rats showed increased maximal tensile strength vs the M group
      (0.09+/-0.01 vs 0.15+/-0.01; P<.05) and similar values of maximal tensile
      strength as the controls (0.15+/-0.01 vs 0.15+/-0.02; P=.91). Collagen type I was
      higher in controls vs the PRE group (6.13+/-0.39 vs 4.90+/-1.53; P<.05);
      nevertheless, the PRE group showed higher collagen type I than M rats (4.90+/
      0.36 vs 3.83+/-0.35; P<.05). CONCLUSIONS: Preoperative feeding for 7 days
      increases the maximal tensile strength, as well as the percentage area of mature
      collagen, approaching similar values as the control group.

PMID- 19164608
TI  - Year-long changes in protein metabolism in elderly men and women supplemented
      with a nutrition cocktail of beta-hydroxy-beta-methylbutyrate (HMB), L-arginine,
      and L-lysine.
AB  - BACKGROUND: A major contributing factor to the loss of mobility in elderly people
      is the gradual and continuous loss of lean body mass. OBJECTIVES: To determine
      whether supplementation of an amino acid cocktail daily for 1 year could improve
      the age-associated changes in protein turnover and lean body mass in elderly
      people. DESIGN: Elderly (76+/-1.6 years) women (n=39) and men (n=38) were
      recruited for a double-blinded controlled study. Study participants were randomly
      assigned to either an isonitrogenous control-supplement (n=37) or a treatment
      supplement (HMB/Arg/Lys) consisting of beta-hydroxy-beta-methylbutyrate, L
      arginine, and L-lysine (n=40) for the 1-year study. Lean tissue mass was measured
      using both bioelectrical-impedance analysis (BIA) and dual energy x-ray
      absorptiometry (DXA). Rates of whole-body protein turnover were estimated using
      primed/intermittent oral doses of 15N-glycine. RESULTS: In subjects taking the
      HMB/Arg/Lys supplement, lean tissue increased over the year of study while in the
      control group, lean tissue did not change. Compared with control, HMB/Arg/Lys
      increased body cell mass (BIA) by 1.6% (P=.002) and lean mass (DXA) by 1.2%
      (P=.05). The rates of protein turnover were significantly increased 8% and 12% in
      the HMB/Arg/Lys-supplemented group while rates of protein turnover decreased 11%
      and 9% in the control-supplemented subjects (P<.01), at 3 and 12 months,
      respectively. CONCLUSIONS: Consumption of a simple amino acid-related cocktail
      increased protein turnover and lean tissue in elderly individuals in a year-long
      study.

PMID- 19164610
TI  - Substrate utilization in the critically ill.

PMID- 19164611
TI  - Knife crime reporting.

PMID- 19164613
TI  - Echocardiography in the emergency department.
AB  - Point-of-care echocardiography using portable machines is an exciting development
      in emergency medicine. Recent improvements in ultrasound quality mean that
      emergency physicians are finding echocardiography useful in a variety of clinical
      settings. Evidence suggests that emergency physicians are able to master the
      skills of basic echocardiography sufficiently to improve patient care in the
      resuscitation scenario. Patients with clinical conditions such as breathlessness,
      undifferentiated shock, chest pain and cardiac arrest may benefit. There is a
      steep learning curve involved in acquiring these skills and the specialty needs
      to take care in the way that its practitioners are accredited and perform
      echocardiography.

PMID- 19164614
TI  - Abdominal and Cardiac Evaluation with Sonography in Shock (ACES): an approach by
      emergency physicians for the use of ultrasound in patients with undifferentiated
      hypotension.
AB  - BACKGROUND: Non-traumatic undifferentiated hypotension is a common critical
      presentation in the emergency department. In this group of patients, early
      diagnosis and goal-directed therapy is essential for an optimal outcome. The
      usefulness of focused bedside ultrasound is reviewed and a protocol for Abdominal
      and Cardiac Evaluation with Sonography in Shock (ACES) is proposed. METHODS: The
      protocol consists of six windows including cardiac, peritoneal, pleural, inferior
      vena cava and aortic views, and aims to shorten the time period taken to
      establish a diagnosis and hence to deliver the most appropriate goal-directed
      therapy. Its use in seven case examples is described. RESULTS: In all cases the
      ACES protocol helped in guiding the initial management while further information
      was obtained. CONCLUSION: The six-view ACES protocol is a useful adjunct to
      clinical examination in patients with undifferentiated hypotension in the
      emergency department. A prospective randomised trial or multicentre
      database/registry is needed to investigate the validity and impact of this
      protocol on the early diagnosis and management of hypotensive patients.

PMID- 19164615
TI  - Interobserver variability in CT scan interpretation for suspected acute
      appendicitis.
AB  - OBJECTIVE: A prospective study was undertaken to assess the interobserver
      variability in CT scan interpretation in patients with suspected acute
      appendicitis. METHODS: 103 adult patients with suspected acute appendicitis
      underwent unenhanced helical multislice CT scanning of the abdomen. All patients
      subsequently underwent laparoscopy by a surgeon who was blind to the diagnosis
      suggested by the CT scan. All CT scans were interpreted by group A, B and C
      radiologists with different levels of expertise. RESULTS: Acute appendicitis was
      diagnosed on multislice CT scans in 69%, 74% and 80% by group A, B, and C
      radiologists, respectively. At laparoscopy, 83% of patients were diagnosed with
      acute appendicitis. For group A, B and C radiologists, the specificity of CT
      scanning for the diagnosis of acute appendicitis was 94%, 94% and 100%,
      respectively, the sensitivity was 81%, 88% and 95%, the positive predictive value
      was 98.6%, 98.7% and 100%, and the negative predictive value was 50%, 68% and
      81%. The difference in the proportion of positive outcomes between observer
      groups A and C was significant. During laparoscopy, 12 patients were diagnosed
      with other diseases. These were all correctly diagnosed by group C radiologists;
      groups A and B radiologists missed the diagnosis of colitis in one patient. All
      other disorders were diagnosed correctly. CONCLUSIONS: The sensitivity of CT
      interpretations for the diagnosis of acute appendicitis differs considerably
      between radiologists. This interobserver variability has to be taken into account
      during implementation of routine CT scanning in patients with suspected acute
      appendicitis. Only in centres with expert CT radiologists is the implementation
      of routine CT scanning in patients with suspected acute appendicitis justified.

PMID- 19164616
TI  - Can a modified thrombolysis in myocardial infarction risk score outperform the
      original for risk stratifying emergency department patients with chest pain?
AB  - BACKGROUND: The thrombolysis in myocardial infarction (TIMI) risk score has been
      shown to risk stratify patients with suspected acute coronary syndromes (ACS)
      effectively in the emergency department (ED) but cannot be used to guide patient
      disposition. We aimed to evaluate whether modifying the TIMI risk score to give
      greater weighting to ischaemic ECG changes and troponin elevations would enhance
      its risk stratification and thus potentially facilitate safe patient discharge
      after 12-h troponin testing. METHODS: A prospective diagnostic cohort study was
      performed within the ED at Manchester Royal Infirmary, a university-affiliated
      teaching hospital with an annual ED census of approximately 145,000 patients. 804
      patients who had presented to the ED with suspected cardiac chest pain were
      recruited. All patients underwent 12-h troponin T testing and were followed up by
      telephone and chart review after 30 days for the composite primary outcome of
      death, acute myocardial infarction (AMI) or urgent coronary revascularisation.
      RESULTS: The modified TIMI risk score outperformed the original (area under the
      receiver operator characteristic curve 0.87 versus 0.77, p<0.001). Using a cut
      off of more than 2 points the score had a sensitivity of 96.4% for the prediction
      of 30-day events. The specificity of the score was only 51.0%, suggesting that in
      practice over 40% of patients would be ineligible for discharge even after
      troponin testing. CONCLUSIONS: Modifications to the TIMI risk score can improve
      its performance in the risk stratification of patients presenting to the ED with
      chest pain. However, a lack of specificity may still limit its use for guiding
      patient disposition after troponin testing.

PMID- 19164617
TI  - Coma and impaired consciousness in the emergency room: characteristics of
      poisoning versus other causes.
AB  - OBJECTIVES: Unconscious patients represent a diagnostic challenge in the
      emergency room (ER), but studies on their characteristics are limited. The aim of
      this study was to investigate the frequency, characteristics and prognosis of
      different coma aetiologies with special focus on poisoning. DESIGN: An
      observational study of consecutive adults admitted to the non-surgical ER, with a
      Glasgow coma scale (GCS) score of 10 or below. The GCS score on admission was
      prospectively entered into a study protocol, which was complemented with data
      from the medical record within one month. RESULTS: 938 patients were enrolled.
      Poisoning caused unconsciousness in 352 cases (38%). In the remaining 586 cases
      (non-poisoning group) the underlying cause was a focal neurological lesion in
      24%, a metabolic or diffuse cerebral disturbance in 21%, epileptogenic in 12%,
      psychogenic in 1% and was still not clarified at hospital discharge in 4%. Among
      patients below the age of 40 years, the coma was caused by poisoning in 80%, but
      among those over 60 years, poisoning was the cause in only 11%. The median GCS
      score on admission was identical in the two study groups. Hospital mortality
      rates were 2.8% and 39% in the two groups, respectively. CONCLUSION: Poisoning
      was the most common cause of coma and young age was a strong predictor of this
      condition. The prognosis was favourable among poisoned patients but poor in the
      rest of the study population as a group.

PMID- 19164618
TI  - Case management of patients who frequently present to a Scottish emergency
      department.
AB  - AIMS: To assess whether case management of frequent attenders to the emergency
      department (ED) reduces subsequent attendances made by these patients. METHODS:
      Patients who attended the ED 10 times or more over a 6-month period were
      identified. Their cases were assessed and care plans put in place, if
      appropriate. Patient attendances over the subsequent 6 months were compared.
      RESULTS: 57 patients attended the ED 10 times or more over the 6-month period
      (1.4% of the departmental workload). The median number of ED attendances in this
      patient group was 12.0 (interquartile range (IQR) 10-14). In the subsequent 6
      months following case management of these patients, median attendances in the
      same 57 patients dropped to 6.0 (IQR 2-13, p<0.001). The total number of
      attendances in this patient group dropped from 720 to 499, a reduction of 31%.
      CONCLUSIONS: The findings of this study suggest that individual case management
      and implementation of care plans may help to reduce subsequent attendances in
      patients who frequently attend ED.

PMID- 19164619
TI  - Imaging the oesophagus after penetrating cervical trauma using water-soluble
      contrast alone: simple, cost-effective and accurate.
AB  - AIM: This audit aims to gauge the safety and efficacy of iso-oncotic water
      soluble contrast media as the sole imaging evaluation of the distal pharynx and
      cervical oesophagus after penetrating cervical trauma. METHODS: A retrospective
      audit was performed over a 4-year period of all patients with penetrating
      cervical trauma to zones 1 and 2 of the neck who were subjected to imaging
      evaluation as part of a selective non-operative management policy for penetrating
      cervical trauma. The outcome was reviewed and the sensitivity, specificity and
      predictive values of the investigation were determined. The surgical management
      of identified injuries is also described. RESULTS: Four hundred and sixty-five
      contrast studies were included with 11 studies positive for pathology (9
      injuries, 2 incidental findings). Surgery was undertaken in 4 patients with
      cervical oesophageal injuries and conservative management was carried out in 5
      cases of distal pharyngeal injury. No missed injuries and no significant adverse
      events were identified during the study period. CONCLUSION: A contrast study of
      the oesophagus with water-soluble iso-oncotic contrast media as the sole
      diagnostic imaging modality is safe (avoiding the risk of aspiration pneumonia),
      reliable (identifying all injuries) and cost-efficient (avoiding the need for
      additional expensive investigations) in cases of penetrating cervical trauma.

PMID- 19164620
TI  - The usefulness of the GlideScope video laryngoscope in the education of
      conventional tracheal intubation for the novice.
AB  - The aim of this study is to evaluate the usefulness of the GlideScope video
      laryngoscope (GVL) as a tool to educate novice users in conventional tracheal
      intubation. 41 premedical students with no previous experience in tracheal
      intubation participated in this prospective, randomised and controlled study.
      Group M (n = 20) was instructed in tracheal intubation by using the Macintosh
      laryngoscope and group G (n = 21) was instructed by using both the GVL and the
      Macintosh laryngoscope. There was no significant difference in tracheal
      intubation performance using the Macintosh laryngoscope between the two groups.
      However, the GVL facilitates the education of tracheal intubation because it
      shows the same anatomical structure for both instructor and trainee
      simultaneously on a real-time basis. This aspect makes the trainee feel more
      comfortable learning the material with a high degree of satisfaction. Introducing
      GVL to conventional intubation education for novice users could increase the
      satisfaction of trainees during the procedure, especially as a way to understand
      critical anatomical structures.

PMID- 19164621
TI  - Airtraq optical laryngoscope: tracheal intubation by novice laryngoscopists.
AB  - OBJECTIVE: To evaluate the performance of the Airtraq optical laryngoscope for
      tracheal intubation by novice laryngoscopists, compared with that of the
      Macintosh laryngoscope. METHODS: Under supervision by staff anaesthetists, non
      anaesthesia physicians performed tracheal intubation using either the Airtraq
      optical laryngoscope (n = 100) or the Macintosh laryngoscope (n = 100). The time
      required for airway instrumentation, the number of attempts until successful
      intubation and erroneous oesophageal intubation were investigated. RESULTS: The
      time to secure the airway was shorter with the Airtraq optical laryngoscope than
      with the Macintosh laryngoscope (p<0.001). The number of attempts until
      successful intubation was smaller with the Airtraq optical laryngoscope than with
      the Macintosh laryngoscope (p<0.001). Erroneous oesophageal intubation was less
      with the Airtraq optical laryngoscope than with the Macintosh laryngoscope
      (p<0.01). CONCLUSION: The Airtraq optical laryngoscope reduces the time to secure
      the airway and the incidence of failed tracheal intubation by novice
      laryngoscopists.

PMID- 19164622
TI  - Critical appraisal for emergency medicine: 6 systematic reviews.

PMID- 19164623
TI  - Best Evidence Topic report. BET 1. Can paramedics accurately perform drug
      calculations?

PMID- 19164625
TI  - Best Evidence Topic report. BET 2. Serum lactate as a marker for mortality in
      patients presenting to the emergency department with trauma.

PMID- 19164626
TI  - Best Evidence Topic report. BET 3. Use of pericardiocentesis for patients with
      cardiac tamponade in penetrating chest trauma.

PMID- 19164627
TI  - Best Evidence Topic report. BET 4. Treating chlamydia in pregnancy.

PMID- 19164628
TI  - Ambulance call triage outcomes for patients reporting pain: a retrospective cross
      sectional analysis of pain score versus triage level.
AB  - OBJECTIVE: To identify any association between the response priority code
      generated during calls to the ambulance communication centre and patient reports
      of pain severity. METHODS: A retrospective analysis of patient care records was
      undertaken for all patients transported by paramedics over a 7-day period. The
      primary research interest was the association between the response code allocated
      at the time of telephone triage and the initial pain severity score recorded
      using a numeric rating scale (NRS). Univariate and multivariate logistic
      regression methods were used to analyse the association between the response
      priority variable and explanatory variables. RESULTS: There were 1246 cases in
      which both an initial pain score using the NRS and a response code were recorded.
      Of these cases, 716/1246 (57.5%) were associated with a code 1 ("time-critical")
      response. After adjusting for gender, age, cause of pain and duration of pain, a
      multivariate logistic regression analysis found no significant change in the odds
      of a patient in pain receiving a time-critical response compared with patients
      who had no pain, regardless of their initial pain score (NRS 1-3, odds ratio (OR)
      1.11, 95% CI 0.7 to 1.8; NRS 4-7, OR 1.12, 95% CI 0.7 to 1.8; NRS 8-10, OR 0.84,
      95% CI 0.5 to 1.4). CONCLUSION: The severity of pain experienced by the patient
      appeared to have no influence on the priority (urgency) of the dispatch response.
      Triage systems used to prioritise ambulance calls and decide the urgency of
      response or type of referral options should consider pain severity to facilitate
      timely and humane care.

PMID- 19164629
TI  - Late-diagnosed diaphragmatic hernia in an 8-year-old girl.

PMID- 19164630
TI  - Influence of air ambulance doctors on on-scene times, clinical interventions,
      decision-making and independent paramedic practice.
AB  - BACKGROUND: Critics of air ambulance doctors question their contribution and
      believe on-scene time is prolonged. Two helicopter emergency medical service
      (HEMS) models operate in the West Midlands, one with doctors and the other
      without. A study was undertaken to compare on-scene time, management and decision
      making between the two units. METHOD: Cases were assessed over an 18-month
      period, identifying on-scene time, incidence of rapid sequence induction (RSI),
      management of patients with a Glasgow Coma Scale (GCS) score of 3, femoral
      fracture, pneumothorax or those with myocardial infarction. RESULTS: There were
      5275 HEMS activations during the study period. The presence of a doctor had no
      effect on on-scene time (27 (2) min vs 26 (2) min, p = NS). Advanced management
      of femoral fractures (nerve block, ketamine or RSI), pneumothorax (chest drain)
      or RSI (when patients were matched for GCS score) by doctors took no longer than
      conventional paramedic management. Doctors performed RSI on 38% of trauma
      patients and 13% of medical patients with a GCS score <15. Patients were more
      likely to be treated and discharged from the scene when seen by a doctor (8.7% vs
      4.6%, p<0.001) and were less likely to be transported to hospital (27% vs 44%,
      p<0.001). For patients with a GCS score of 3, doctors were more likely to cease
      resuscitation efforts and confirm death at the scene (70% vs 16%, p<0.001).
      CONCLUSIONS: Appropriately trained HEMS doctors provide advanced management and
      decision-making. This is without a negative effect on on-scene time, even when
      performing complex procedures. They are more likely to declare death or discharge
      patients at the scene, increasing the availability of this limited resource.

PMID- 19164631
TI  - Designing emergency ambulances for the 21st century.
AB  - BACKGROUND: In 2005 the Department of Health set out a vision for the provision
      of future ambulance services with an increasing range of quality mobile
      healthcare services for patients with urgent and emergency care needs. This paper
      describes a scoping study funded by the National Patient Safety Agency and
      Ambulance Service Association to investigate the short and longer term
      requirements of future emergency ambulances. METHOD: Four stakeholder workshops
      were held to explore the wishes, concerns and preferences of the clinicians,
      operational staff and manufacturers about the future provision of ambulance
      services and problems and possible solutions relating to ambulance design and
      use. Incident reports relating to ambulance design and use were reviewed from
      three national and international databases. RESULTS: Nine design challenges were
      identified: access/egress; space and layout; securing people and equipment in
      transit; communication; security, violence and aggression; hygiene; equipment;
      vehicle engineering; patient experience. These were validated at the national UK
      ambulance conference (AMBEX 2006) with a rating questionnaire. CONCLUSION: The
      results are being used in the development of a national specification for future
      UK emergency ambulances.

PMID- 19164632
TI  - Treatment of presumed acute cardiogenic pulmonary oedema in an ambulance system
      by nurses using Boussignac continuous positive airway pressure.
AB  - BACKGROUND: Early initiation of continuous positive airway pressure (CPAP)
      applied by face mask benefits patients with acute cardiogenic pulmonary oedema
      (ACPE). The simple disposable Boussignac CPAP (BCPAP) has been used in ambulances
      by physicians. In the Netherlands, ambulances are manned by nurses and not
      physicians. It was hypothesised that ambulance nurses are able to identify
      patients with ACPE and can successfully apply BCPAP. A prospective case series of
      patients with presumed ACPE treated with BCPAP by ambulance nurses is described.
      METHODS: After training of ambulance nurses, all 33 ambulances in the region were
      equipped with BCPAP. ACPE was diagnosed on clinical signs and pulse oximetry
      saturation (Spo(2)) <95%. BCPAP (5 cm H(2)O, Fio(2)>80%) was generated with an
      oxygen flow of 15 l/min. The physiological responses, experiences and clinical
      outcomes of the patients were collected from ambulance and hospital records, and
      ambulance nurses and patients received a questionnaire. RESULTS: From March to
      December 2006, 32 patients (age range 61-94 years) received BCPAP during
      transport to six different regional hospitals. In 26 patients (81%) a diagnosis
      of ACPE was confirmed. With BCPAP, median (IQR) Spo(2) increased from 79% (69
      94%) to 96% (89-98%) within 20 min. The median (IQR) duration of BCPAP treatment
      was 26 min (21-32). The patients had no negative recollections of the treatment.
      Ambulance personnel were satisfied with the BCPAP therapy. CONCLUSION: When
      applied by ambulance nurses, BCPAP was feasible and effective in improving oxygen
      saturation in patients with ACPE. Although survival benefit can only be
      demonstrated by further research, it is considered that BCPAP can be implemented
      in all ambulances in the Netherlands.

PMID- 19164633
TI  - Tension pneumothorax secondary to automatic mechanical compression decompression
      device.
AB  - The details are presented of the first published case of a tension pneumothorax
      induced by an automatic compression-decompression (ACD) device during cardiac
      arrest. An elderly patient collapsed with back pain and, on arrival of the crew,
      was in pulseless electrical activity (PEA) arrest. He was promptly intubated and
      correct placement of the endotracheal tube was confirmed by noting equal air
      entry bilaterally and the ACD device applied. On the way to the hospital he was
      noted to have absent breath sounds on the left without any change in the position
      of the endotracheal tube. Needle decompression of the left chest caused a hiss of
      air but the patient remained in PEA. Intercostal drain insertion in the emergency
      department released a large quantity of air from his left chest but without any
      change in his condition. Post-mortem examination revealed a ruptured abdominal
      aortic aneurysm as the cause of death. Multiple left rib fractures and a left
      lung laceration secondary to the use of the ACD device were also noted, although
      the pathologist felt that the tension pneumothorax had not contributed to the
      patient's death. It is recommended that a simple or tension pneumothorax should
      be considered when there is unilateral absence of breath sounds in addition to
      endobronchial intubation if an ACD device is being used.

PMID- 19164634
TI  - Stuck in the mud: an unusual football injury.

PMID- 19164635
TI  - Splenic injury as a rare complication of colonoscopy.
AB  - Injury resulting from colonoscopy is rare. Bleeding and perforation are the most
      serious complications. The case history is described of a patient who developed
      splenic rupture following screening colonoscopy with associated polypectomy.

PMID- 19164636
TI  - Achalasia: an unusual cause of airway obstruction.
AB  - Achalasia is a disorder of the lower oesophageal sphincter and the smooth
      musculature of the oesophageal body. Although oesophageal obstruction is common,
      concurrent airway obstruction is exceptional. A case is presented of a 79-year
      old woman admitted to the emergency department requiring intubation following out
      of-hospital airway obstruction and subsequent respiratory arrest.

PMID- 19164638
TI  - Patient examination.

PMID- 19164639
TI  - No Wii cause for concern.

PMID- 19164640
TI  - A combined alcohol and drugs counselling service model in an emergency
      department.

PMID- 19164642
TI  - Ventricular tachycardia following snakebite envenoming.

PMID- 19164643
TI  - Non-trauma CT head scans in the emergency department: are we doing too much?

PMID- 19164644
TI  - Could new communication systems be used to advise public in emergency situations?
      The HSDPA/WCDMA-based video telephony application to pre-hospital care medicine.

PMID- 19164645
TI  - The Licensing Act and emergency hospital attendances.

PMID- 19164646
TI  - Pneumperitoneum due to chest compressions.

PMID- 19164647
TI  - Mandibular fracture caused by mastication.

PMID- 19164649
TI  - Stress in junior enlisted air force women with and without children.
AB  - The objective was to determine if there are differences between young enlisted
      military women with and without preschool children on role strain, stress,
      health, and military career aspiration and to identify the best predictors of
      these variables. The study used a cross-sectional descriptive design of 50 junior
      Air Force women with preschool children and 50 women without children. There were
      no differences between women with and without children in role strain, stress,
      health, and military career aspiration. In all women, higher stress was
      moderately predictive of higher role strain (39.9% of variance explained) but a
      poor predictor of career aspiration (3.8% of variance explained). Lower mental
      health scores were predicted by high stress symptoms (27.9% of variance
      explained), low military career aspiration (4.1% of variance explained), high
      role strain (4.0% of variance explained), and being non-White (3.9% of variance
      explained). Aspiration for a military career was predicted by high perceived
      availability of military resources (16.8% of variance explained), low family of
      origin socioeconomic status (4.5% of variance explained), and better mental
      health status (3.3% of variance explained). Contrary to theoretical expectations,
      in this sample, motherhood was not a significant variable. Increased role strain,
      stress, and decreased health as well as decreased military career aspiration were
      evident in both groups and may have more to do with individual coping skills and
      other unmeasured resources. More research is needed to determine what nursing
      interventions are needed to best support both groups of women.

PMID- 19164650
TI  - Psychometric analysis of the Inventory of Functional Status--Cancer (IFS-CA) in
      Turkish women.
AB  - The aim of this study was to test the reliability and validity of the Turkish
      version of the Inventory of Functional Status- Cancer (IFS-CA). The questionnaire
      was composed of four subscales that measured to what extent a woman maintained
      her usual household and family, social and community, personal care, and
      occupational activities. Internal consistency reliability using average
      correlations for the subscale item to subscale total scores ranged from .21 to
      .97. Construct validity was accomplished by examination of subscale correlations,
      which ranged from -.10 to .70. The Turkish version of the IFS-CA is found to be
      psychometrically reliable and valid.

PMID- 19164651
TI  - Nurse migration to Canada: pathways and pitfalls of workforce integration.
AB  - Many internationally educated nurses (IENs) find it difficult to reinstate
      themselves in their profession after migration. This article explores factors
      contributing to the success and failure of IENs to reestablish professional
      careers. The article discusses a study involving 39 IENs in 5 focus groups and 10
      interviews. In all, 29 interviews are held with other stakeholders. IENs
      encounter obstacles at each stage of the migration process. New strategies are
      required to assist IENs to reenter the workforce. Given the consistent
      predictions of an extreme nurse shortage, it is important that the brain waste of
      immigrant nurses be minimized.

PMID- 19164652
TI  - Language used by Korean and Korean American children to describe emotional
      reactions to illness and hospitalization.
AB  - Most children experience emotional distress during hospitalization. However,
      existing instruments for assessing emotional status in hospitalized children have
      limitations. To address this, the authors determine the language that Korean and
      Korean American children use to describe emotions that may relate to illness and
      hospitalization. Using a descriptive exploratory design, projective method, and
      card sort, the study is conducted in six Korean ethnic churches in the Midwest
      metropolitan area of United States and uses a convenience sample consisting of 94
      children, ages 7 to 12 years. Fifteen English emotion words and 13 Korean emotion
      words are chosen by at least 50% of the Korean-American and Korean children, and
      children's emotional responses are expressed differently in Korean and English.
      Health care providers should be cautious about direct translation, because
      cultural nuances can convey different meanings in another language. In
      preparation for the rapid growth of minority children in the United States,
      health care providers should understand cultural perspectives related to minority
      children's experiences of health and illness and provide linguistically and
      culturally appropriate care.

PMID- 19164653
TI  - Invited review: Genomic selection in dairy cattle: progress and challenges.
AB  - A new technology called genomic selection is revolutionizing dairy cattle
      breeding. Genomic selection refers to selection decisions based on genomic
      breeding values (GEBV). The GEBV are calculated as the sum of the effects of
      dense genetic markers, or haplotypes of these markers, across the entire genome,
      thereby potentially capturing all the quantitative trait loci (QTL) that
      contribute to variation in a trait. The QTL effects, inferred from either
      haplotypes or individual single nucleotide polymorphism markers, are first
      estimated in a large reference population with phenotypic information. In
      subsequent generations, only marker information is required to calculate GEBV.
      The reliability of GEBV predicted in this way has already been evaluated in
      experiments in the United States, New Zealand, Australia, and the Netherlands.
      These experiments used reference populations of between 650 and 4,500 progeny
      tested Holstein-Friesian bulls, genotyped for approximately 50,000 genome-wide
      markers. Reliabilities of GEBV for young bulls without progeny test results in
      the reference population were between 20 and 67%. The reliability achieved
      depended on the heritability of the trait evaluated, the number of bulls in the
      reference population, the statistical method used to estimate the single
      nucleotide polymorphism effects in the reference population, and the method used
      to calculate the reliability. A common finding in 3 countries (United States, New
      Zealand, and Australia) was that a straightforward BLUP method for estimating the
      marker effects gave reliabilities of GEBV almost as high as more complex methods.
      The BLUP method is attractive because the only prior information required is the
      additive genetic variance of the trait. All countries included a polygenic effect
      (parent average breeding value) in their GEBV calculation. This inclusion is
      recommended to capture any genetic variance not associated with the markers, and
      to put some selection pressure on low-frequency QTL that may not be captured by
      the markers. The reliabilities of GEBV achieved were significantly greater than
      the reliability of parental average breeding values, the current criteria for
      selection of bull calves to enter progeny test teams. The increase in reliability
      is sufficiently high that at least 2 dairy breeding companies are already
      marketing bull teams for commercial use based on their GEBV only, at 2 yr of age.
      This strategy should at least double the rate of genetic gain in the dairy
      industry. Many challenges with genomic selection and its implementation remain,
      including increasing the accuracy of GEBV, integrating genomic information into
      national and international genetic evaluations, and managing long-term genetic
      gain.

PMID- 19164654
TI  - Fate of lysostaphin in milk from individual cows through pasteurization and
      cheesemaking.
AB  - Transgenic cows secreting over 3 microg of lysostaphin/ mL of milk are protected
      against mastitis caused by Staphylococcus aureus, but it is unknown if active
      lysostaphin persists through dairy processing procedures or affects the
      production of fermented dairy foods. The objective of this study was to determine
      the fate of lysostaphin as milk was pasteurized and then processed into cheese.
      Raw milk from transgenic cows was heat treated at 63 degrees C for 30 min, 72
      degrees C for 15 s (high temperature, short time), or 140 degrees C for 2 s
      (UHT). Portions of the high temperature, short-time milk were manufactured into
      semi-hard cheeses. Aliquots taken at each processing step were assayed to
      determine the quantity (ELISA) and activity (ability to inhibit S. aureus growth)
      of lysostaphin. Results indicated that most of the lysostaphin was present in the
      aqueous portion of the milk and was not affected by pasteurization, although UHT
      treatment reduced enzyme concentration by 60%. The quantity and activity of the
      lysostaphin decreased during cheesemaking. Based on the amount of lysostaphin
      present in the starting cheesemilk, 10 to 15% of the lysostaphin was recovered in
      the whey, 21 to 55% in the cheese curd at d 1, and 21 to 36% in cheese stored at
      4 degrees C for 90 d. Enough of the lysostaphin secreted into milk by transgenic
      cows survived typical dairy processing conditions to impart potential value as a
      bioprotective agent against staphylococci in dairy foods.

PMID- 19164655
TI  - The influence of temperature and pressure factors in supercritical fluid
      extraction for optimizing nonpolar lipid extraction from buttermilk powder.
AB  - The milk fat globule membrane, readily available in buttermilk, contains complex
      lipids claimed to be beneficial to humans. Phospholipids, including
      sphingolipids, exhibit antioxidative, anticarcinogenic, and antiatherogenic
      properties and have essential roles in numerous cell functions. Microfiltration
      coupled with supercritical fluid extraction (SFE) may provide a method for
      removing triacylglycerols while concentrating these nutritionally valuable lipids
      into a novel ingredient. Therefore, SFE as a method for phospholipid
      concentration needs to be optimized for triacylglycerol removal in buttermilk.
      The SFE conditions were assessed using a general full factorial design; the
      experimental factors were pressure (15, 25, and 35 MPa) and temperature (40, 50,
      and 60 degrees C). Particularly interesting is that only triacylglycerols were
      removed from buttermilk powder. Little to no protein loss or aggregation was
      observed compared with the untreated buttermilk powder. Calculated theoretical
      values showed a linear increase for lipid solubility as pressure, temperature, or
      both were increased; however, experimental values showed nonlinearity, as an
      effect of temperature. In addition, the particular SFE parameters of 35 MPa and
      50 degrees C displayed enhanced extraction efficiency (70% total lipid
      reduction).

PMID- 19164656
TI  - Effect of the inclusion of whole citrus in the ration of lactating ewes on the
      properties of milk and cheese characteristics during ripening.
AB  - The effect of including citrus fruits (CF) in the rations of dairy ewes on the
      milk characteristics and biochemical changes of cheeses during ripening was
      evaluated. For this purpose, 48 lactating ewes (Guirra breed) were divided into 4
      homogeneous groups and fed with isoenergetic and isoprotein rations containing CF
      at 0, 10, 20, and 30% on a dry matter basis in substitution of dry barley and
      pelleted beet pulp. During the experimental period, 3 batches of bulk milk were
      collected from each group and semi-hard cheeses were manufactured. Cheeses were
      sampled at 15, 30, and 60 d of ripening. Milk coagulation parameters and cheese
      yield were not negatively affected by the inclusion of CF in the ration.
      Physicochemical composition of cheeses at 60 d showed statistical differences for
      lower total solids and fat content of 30% CF cheeses. Proteolysis of cheeses
      measured by water-soluble nitrogen and total free amino acids content was not
      influenced by the ration. Differences between rations with respect to free fatty
      acids were significant for medium- and long-chain free fatty acids, and therefore
      for total content, but differences did not show a trend related to the increase
      of CF in the diet. The inclusion of CF in the ration of lactating ewes up to
      levels of 30% did not negatively affect the properties of milk and the
      biochemical and sensory characteristics of cheeses.

PMID- 19164657
TI  - Fat-free yogurt made using a galactose-positive exopolysaccharide-producing
      recombinant strain of Streptococcus thermophilus.
AB  - To prevent textural defects in low-fat and fat-free yogurts, fat substitutes are
      routinely added to milk. In situ production of exopolysaccharides (EPS) by
      starter cultures is an acknowledged alternative to the addition of biothickeners.
      With the aim of increasing in situ EPS production, a recombinant galactose
      positive EPS(+) Streptococcus thermophilus strain, RD-534-S1, was generated and
      compared with the parent galactose-negative EPS(+) strain RD-534. The RD-534-S1
      strain produced up to 84 mg/L of EPS during a single-strain milk fermentation
      process, which represented 1.3 times more than the EPS produced by strain RD-534.
      Under conditions that mimic industrial yogurt production, the starter culture
      consisting of RD-534-S1 and (EPS(-)) Lactobacillus bulgaricus L210R strain (RD
      534-S1/L210R) led to an EPS production increase of 1.65-fold as compared with RD
      534-S1 alone. However, the amount of EPS produced did not differ from that found
      in yogurts produced using an isogenic starter culture that included the parent S.
      thermophilus strain RD-534 and Lb. bulgaricus L210R (RD-534/L210R). Moreover, the
      gel characteristics of set-style yogurt and the rheological properties of stirred
      style yogurt produced using RD-534-S1/L210R were similar to the values obtained
      for yogurts made with RD-534/L210R. In conclusion, it is possible to increase the
      production of EPS by ropy S. thermophilus strains through genetic engineering of
      galactose metabolism. However, when used in combination with Lb. bulgaricus for
      yogurt manufacture, the EPS overproduction of recombinant strain is not
      significant.

PMID- 19164658
TI  - Shelf life of Stracciatella cheese under modified-atmosphere packaging.
AB  - The aim of this work is to evaluate the shelf life of Stracciatella cheese
      packaged in a protective atmosphere, using 4 different CO(2):N(2):O(2) gas
      mixtures [50:50:0 (M1), 95:5:0 (M2), 75:25:0 (M3), and 30:65:5 (M4) vol/vol] and
      stored at 8 degrees C. Cheese in traditional tubs and under vacuum were used as
      the controls. Results showed that the modified-atmosphere packaging, in
      particular M1 and M2, delayed microbial growth of spoilage bacteria, without
      affecting the dairy microflora, and prolonged the sensorial acceptability limit.

PMID- 19164659
TI  - Immobilization of recombinant thermostable beta-galactosidase from Bacillus
      stearothermophilus for lactose hydrolysis in milk.
AB  - A recombinant thermostable beta-galactosidase from Bacillus stearothermophilus
      was immobilized onto chitosan using Tris(hydroxymethyl)phosphine (THP) and
      glutaraldehyde, and a packed bed reactor was utilized to hydrolyze lactose in
      milk. The thermostability and enzyme activity of THP-immobilized beta
      galactosidase during storage was superior to that of free and glutaraldehyde
      immobilized enzymes. The THP-immobilized beta-galactosidase showed greater
      relative activity in the presence of Ca(2+) than the free enzyme and was stable
      during the storage at 4 degrees C for 6 wk, whereas the free enzyme lost 31% of
      the initial activity under the same storage conditions. More than 80% of lactose
      hydrolysis in milk was achieved after 2 h of operation in the reactor. Therefore,
      THP-immobilized recombinant thermostable beta-galactosidase from Bacillus
      stearothermophilus has the potential for application in the production of lactose
      hydrolyzed milk.

PMID- 19164660
TI  - Effects of body weight and nutrition on histological mammary development in
      Holstein heifers.
AB  - Our objective was to determine the effects of rate of gain and body weight (BW)
      on development of the mammary parenchyma. Mammary tissue samples were collected
      from heifers (n = 72) reared on 1 of 2 dietary treatments (restricted, 650 g/d of
      daily gain; or elevated, 950 g/d of daily gain) and slaughtered at 100, 150, 200,
      250, 300, or 350 kg of BW. Mammary samples were excised, preserved, prepared for
      histology, and stained with hematoxylin and eosin. Digital images of tissue
      sections were captured for analysis. Tissue areas occupied by the interlobular
      and intralobular stroma, epithelium, and lumen were measured (mum(2)). The
      numbers of epithelial and luminal structures per image were tabulated to measure
      the complexity of ductal development. Mean percentages of mammary parenchyma
      occupied by the interlobular stroma, epithelium, lumen, and intralobular stroma
      were 29, 20, 7, and 43%, respectively. Percentage of area occupied by the
      intralobular stroma was affected by BW and was lower for 100-kg heifers compared
      with heifers 200 kg and heavier (33 +/- 4 vs. 46 +/- 4), but the percentage of
      area occupied by other tissue elements did not differ by BW or treatment, nor was
      there an interaction. However, the numbers of both epithelial (8.3 +/- 4 vs. 47
      +/- 4) and luminal-containing (6 +/- 4 vs. 38 +/- 4) structures per image
      increased markedly between 100 and 350 kg of BW, irrespective of diet. For
      heifers slaughtered between 100 and 350 kg of BW, alterations in the rate of gain
      between 650 and 950 g/d, accomplished by feeding varying amounts of the same
      diet, had no significant effect on tissue characteristics or the pattern of
      mammary parenchymal development. These data emphasize the importance of BW and
      age in determining developmental characteristics of the heifer mammary parenchyma
      and suggest that the rate of gain per se has a minimal impact on histological
      development, and thus do not support the hypothesis that rate of gain has a
      direct negative impact on ductal development.

PMID- 19164661
TI  - Effects of shade and sprinklers on performance, behavior, physiology, and the
      environment of heifers.
AB  - The objective was to measure effects of cooling technique (shade vs. water
      sprinklers) on performance, behavior, physiology, and the environmental effect of
      40 Holstein heifers housed in drylot corrals during the hot summer months. The
      experiment was a replicated crossover design with four 21-d periods and 2
      treatments: 1) shades installed in the front half of the pen or 2) sprinklers,
      which applied water to the pen surface at 2-h intervals from 1100 to 1900 h.
      Animal performance measures were dry matter intake, average daily gain, and feed
      efficiency (gain:feed). Behavioral measures, elimination patterns, and corral
      spatial distribution were measured in 5-min scan frequencies over four 24-h
      periods. Physiological measures were rectal temperature, respiration rate,
      urinary urea N, and blood urea N. Environmental measures were corral soil surface
      temperature and moisture, particulate matter, and surface NH(3) volatilization;
      meteorological measures were also collected. Shaded compared with sprinkled
      heifers had increased dry matter intake (3.4%), increased average daily gain
      (14%), and increased feed efficiency (11%). Heifers in shaded vs. sprinkler
      treatments had decreased respiration rates (13%). Behavioral differences between
      the treatments varied by time of day. Heifers spent most time in either the
      shaded or sprinkled areas of their corrals (65.9 and 64.2%, respectively).
      Elimination behavior occurred predominantly at the front of the corral in close
      proximity to the feed bunks and additionally at the water trough in sprinkled
      corrals. Sprinkler treatment had a 31.7% greater average corral surface moisture
      than the shaded treatment. Corral surface temperature varied based on areas of
      surface moisture, shade location, and elimination concentration within the
      corral. Sprinkled corrals had less particulate matter emissions than shaded
      (25%), but NH(3) emissions were 46% greater in sprinkler vs. shaded treatment.
      Overall, the use of shade in heifer corrals improved heifer performance and
      physiological measures, but sprinkler treatment had less PM [corrected] emissions
      from corral surfaces under heat stress conditions. Both cooling techniques
      affected spatial distribution and behaviors of the heifers, which affected pen
      usage and surface characteristics.

PMID- 19164662
TI  - Immune responses of Holstein and Norwegian Red x Holstein calves on Canadian
      dairy farms.
AB  - The objective of this study was to compare the immune response of Holstein and
      Norwegian Red x Holstein calves on 13 commercial Canadian dairy farms. Data were
      collected on 135 calves, 68 Holstein and 67 Norwegian Red x Holstein calves aged
      between 2 and 6 mo. The calves were immunized with hen egg white lysozyme to
      induce antibody-mediated immune response. Candida albicans was used as an in vivo
      indicator of cell-mediated immune response, with delayed-type hypersensitivity
      used as the indicator. Antibody response to hen egg white lysozyme (IgG, IgG1,
      and IgG2) was measured by ELISA. Calves of both breed groups produced a
      significant primary and secondary antibody-mediated immune response, as well as a
      delayed-type hypersensitivity reaction. The Norwegian Red x Holstein produced a
      greater primary IgG antibody-mediated immune response (d 14, and d 14 minus d 0)
      when compared with the Holstein. No differences were observed between the breeds
      for secondary response or antihen egg white lysozyme isotype (IgG1 or IgG2)
      production or the ratio of IgG1:IgG2. There was no effect of breed on delayed
      type hypersensitivity. Nonetheless, high and low immune responders could be
      identified in both breed groups, but with no difference in the proportion of high
      and low responders observed for either antibody-mediated immune response or cell
      mediated immune response between breed groups.

PMID- 19164663
TI  - Somatotropic axis components and nutrient partitioning in genetically diverse
      dairy cows managed under different feed allowances in a pasture system.
AB  - The somatotropic axis [including growth hormone (GH), GH receptor, and insulin
      like growth factor (IGF)-I] is uncoupled in high-producing cows in early
      lactation so that the liver fails to respond to GH and produces less IGF-I. This
      uncoupling was implicated in the process of nutrient partitioning, enabling high
      milk production. Different genetic selection goals may affect functional
      components of the somatotropic axis. Thus, the somatotropic axis was examined in
      diverse genetic strains of dairy cows [North American Holstein 1990 (NA90), New
      Zealand Holstein-Friesian 1990 (NZ90), and New Zealand Holstein-Friesian 1970
      (NZ70)] that were managed similarly within a pasture-based system but were
      offered feed allowances commensurate with their genetic ability to produce milk.
      The NA90 cows produced more milk (26.2 +/- 0.3, 24.1 +/- 0.3, and 20.1 +/- 0.4
      kg/d, for NA90, NZ90, and NZ70, respectively), but had lower milk fat percentages
      (4.28 +/- 0.03, 4.69 +/- 0.03, and 4.58 +/- 0.04 kg/d for NA90, NZ90, and NZ70,
      respectively) compared with both NZ strains. Milk protein percentages (3.38 +/-
      0.02, 3.52 +/- 0.02, and 3.29 +/- 0.03 kg/d for NA90, NZ90, and NZ70,
      respectively) were greater for NZ90 cows. During early lactation (wk 2 to 6), the
      total net energy produced in milk was greater in NA90 compared with NZ90 or NZ70
      cows, but total net energy in milk after wk 6 was equivalent for NA90 and NZ90
      cows. The greater milk production in early lactation in NA90 cows was associated
      with lower body condition scores (BCS; 1 to 10 scale; 4.0 +/- 0.1) elevated blood
      GH concentrations (1.6 +/- 0.1 ng/mL), and low blood IGF-I concentrations (14.8
      +/- 1.1 ng/mL), indicating an uncoupled somatotropic axis. In comparison, the
      NZ70 cows retained a coupled somatotropic axis during early lactation,
      maintaining greater BCS (4.6 +/- 0.1), lower blood GH (0.7 +/- 0.1 ng/mL), and
      greater blood IGF-I (21.9 +/- 1.2 ng/mL). The degree of uncoupling in NZ90 cows
      was intermediate between the other 2 strains. Additional feed allowance failed to
      change blood IGF-I concentrations in NA90 cows but increased IGF-I concentrations
      in NZ90 cows (20.9 +/- 1.4 and 13.2 +/- 1.4 ng/mL for the high and low feed
      allowance, respectively). Furthermore, additional feed allowance in NZ90 cows
      lessened BCS loss in early lactation, but did not affect BCS loss in NA90 cows.
      Functional components of the somatotropic axis differed for the respective
      strains and were consistent with strain differences in milk production, BCS, and
      feed allowance.

PMID- 19164664
TI  - The impact of meloxicam on postsurgical stress associated with cautery dehorning.
AB  - The objectives were to determine the duration of the stress response associated
      with cautery dehorning and to assess the effectiveness of the nonsteroidal anti
      inflammatory drug meloxicam (Metacam, 20 mg/mL solution for injection) for
      reducing that response. Sixty Holstein heifer calves were blocked by age and
      randomly assigned to receive an i.m. injection of meloxicam or a placebo (0.5
      mg/kg). All calves were given a lidocaine cornual nerve block delivered 5 mL per
      side 10 min before dehorning. To establish baseline values, calves were sham
      dehorned 24 h before actual dehorning. Blood samples were taken via indwelling
      jugular catheters at 0, 0.5, 1, 1.5, 2, 4, 6, and 24 h after the procedure. Heart
      and respiratory rates were also taken at these times. Data were analyzed using
      PROC MIXED in SAS. Analysis of covariance was employed to assess the difference
      between sham and dehorning at each time period. Dehorning was associated with
      elevated serum cortisol (d -1: 33.9 +/- 1.26; d 0: 46.2 +/- 2.33 nmol/L) and
      heart rate (d -1: 108 +/- 1.8; d 0: 109.4 +/- 2.4 beats per minute) in both
      groups for 24 h, and elevated respiratory rate (sham: 42.2 +/- 1.95 vs.
      dehorning: 45.1 +/- 2.19 respirations per minute) in both groups for 6 h. A
      treatment x time interaction was found for cortisol, with meloxicam calves having
      lower serum cortisol than controls until 6 h after dehorning (meloxicam: 49.7 +/-
      4.37 vs. control: 63.0 +/- 6.94 nmol/L). There was no difference between the
      treatment groups at 24 h (meloxicam: 35.2 +/- 2.74 and control: 34.8 +/- 3.64
      nmol/L of cortisol). Overall, the changes in heart rates (increase meloxicam:
      3.74 +/- 0.96 vs. control: 4.70 +/- 1.87) and respiratory rates (increase
      meloxicam: 2 +/- 0.1 vs. control: 4 +/- 0.2) were greater in the control group
      compared with the meloxicam group. These results indicate that meloxicam reduced
      the physiological stress response to dehorning.

PMID- 19164665
TI  - Exercise training of late-pregnant and nonpregnant dairy cows affects physical
      fitness and acid-base homeostasis.
AB  - The objective was to determine if exercise training improves physical fitness of
      nonlactating, late-pregnant and nonpregnant multiparous Holstein cows and alters
      acid-base homeostasis during an exercise test on a treadmill. Twenty-six pairs
      (each pair having 1 late-pregnant and 1 nonpregnant) of cows were assigned to
      treatments of exercise training or no exercise. Exercise training was walking
      (1.25 to 1.5 h at 3.25 km/h) every other day in an outdoor mechanical walker for
      70 d. Cows completed treadmill exercise tests on d 0, 30, and 60 of the
      experiment or about d 70, 40, and 10 before expected parturition of the pregnant
      cow of each pair. On d 0, physical fitness was similar among all cows based on
      durations of treadmill tests, heart rates, and acid-base measurements at given
      workloads (21.1 +/- 0.6 min; 144 +/- 2.2 beats per min; plasma lactate 3.1 +/-
      1.9 mmol/L; and venous blood pH 7.44 +/- 0.0035, respectively). After 60 d of
      training, exercised cows walked longer during treadmill exercise tests compared
      with nonexercised cows (23.7 vs. 18.3 +/- 0.85 min, respectively), indicating
      greater physical fitness (pooled across pregnancy status). Heart rates and plasma
      lactate concentrations at given workloads were less (144 vs. 156 +/- 2.7 beats
      per min; and 1.4 vs. 3.2 +/- 0.24 mmol/L for exercised compared with nonexercised
      cows, respectively). Additionally, exercised cows more effectively maintained
      acid-base homeostasis during treadmill tests compared with nonexercised cows.
      Metabolic, endocrine, and nutritional demands associated with late pregnancy did
      not affect responses differently to exercise training for late-pregnant compared
      with nonpregnant cows. Overall, exercise training of late-pregnant and
      nonpregnant cows for 60 d improved physical fitness.

PMID- 19164666
TI  - Developmental competence of bovine embryos from heat-stressed ova.
AB  - Because multiple ovulation embryo transfer procedures are occasionally performed
      in cows experiencing heat stress, the goal of this study was to assess the
      developmental competence of otherwise morphologically normal embryos from heat
      stressed ova. To this end, the ability of compact morulae from heat-stressed and
      non-heat-stressed bovine ova to undergo blastocyst development after culture at
      38.5 or 41.0 degrees C was examined. It was hypothesized that heat-induced
      perturbations in the ooplasm carry over to increase the susceptibility of the
      preattachment embryo to heat stress. Initially, ova were matured at 38.5 or 41.0
      degrees C. The consequences of heat stress did not include altered cleavage, but
      did reduce the proportion of 8- to 16-cell-stage embryos (55.3 vs. 50.6%; SEM +/-
      1.9). Although proportionately fewer, compact morulae from heat-stressed ova were
      equivalent in quality to those from non-heat-stressed ova (2.1 and 2.1; SEM =
      0.04). Culture of compact morulae from non-heat-stressed ova at 41.0 degrees C
      did not affect blastocyst development (71.9 and 71.5%; SEM = 3.0). Furthermore,
      the development of compact morulae from heat-stressed ova was similar to that of
      non-heat-stressed ova after culture at 38.5 degrees C (68.2 vs. 71.9 and 71.5%;
      SEM = 3.0). However, blastocyst development was reduced when compact morulae from
      heat-stressed ova were cultured at 41.0 degrees C (62.3 vs. 71.9, 71.5 and 68.2;
      SEM = 3.1). In summary, reduced compaction rates of heat-stressed ova explained
      in part why fewer develop to the blastocyst stage after fertilization. The
      thermolability of the few embryos that develop from otherwise developmentally
      challenged ova emphasizes the importance of minimizing exposure to stressor(s)
      during oocyte maturation.

PMID- 19164667
TI  - Impact of hyperketonemia in early lactation dairy cows on health and production.
AB  - Data from 1,010 lactating lactating, predominately component-fed Holstein cattle
      from 25 predominately tie-stall dairy farms in southwest Ontario were used to
      identify objective thresholds for defining hyperketonemia in lactating dairy
      cattle based on negative impacts on cow health, milk production, or both. Serum
      samples obtained during wk 1 and 2 postpartum and analyzed for beta
      hydroxybutyrate (BHBA) concentrations that were used in analysis. Data were time
      ordered so that the serum samples were obtained at least 1 d before the disease
      or milk recording events. Serum BHBA cutpoints were constructed at 200 micromol/L
      intervals between 600 and 2,000 micromol/L. Critical cutpoints for the health
      analysis were determined based on the threshold having the greatest sum of
      sensitivity and specificity for predicting the disease occurrence. For the
      production outcomes, models for first test day milk yield, milk fat, and milk
      protein percentage were constructed including covariates of parity, precalving
      body condition score, season of calving, test day linear score, and the random
      effect of herd. Each cutpoint was tested in these models to determine the
      threshold with the greatest impact and least risk of a type 1 error. Serum BHBA
      concentrations at or above 1,200 micromol/L in the first week following calving
      were associated with increased risks of subsequent displaced abomasum [odds ratio
      (OR) = 2.60] and metritis (OR = 3.35), whereas the critical threshold of BHBA in
      wk 2 postpartum on the risk of abomasal displacement was >or=1,800 micromol/L (OR
      = 6.22). The best threshold for predicting subsequent risk of clinical ketosis
      from serum obtained during wk 1 and wk 2 postpartum was 1,400 micromol/L of BHBA
      (OR = 4.25 and 5.98, respectively). There was no association between clinical
      mastitis and elevated serum BHBA in wk 1 or 2 postpartum, and there was no
      association between wk 2 BHBA and risk of metritis. Greater serum BHBA measured
      during the first and second week postcalving were associated with less milk
      yield, greater milk fat percentage, and less milk protein percentage on the first
      Dairy Herd Improvement test day of lactation. Impacts on first Dairy Herd
      Improvement test milk yield began at BHBA >or=1,200 micromol/L for wk 1 samples
      and >or=1,400 micromol/L for wk 2 samples. The greatest impact on yield occurred
      at 1,400 micromol/L (-1.88 kg/d) and 2,000 micromol/L (-3.3 kg/d) for sera from
      the first and second week postcalving, respectively. Hyperketonemia can be
      defined at 1,400 micromol/L of BHBA and in the first 2 wk postpartum increases
      disease risk and results in substantial loss of milk yield in early lactation.

PMID- 19164668
TI  - Weight distribution and gait in dairy cattle are affected by milking and late
      pregnancy.
AB  - There is increased interest in automated methods for lameness detection, such as
      measures of weight distribution. Still, practical use of such methods depends on
      knowing the conditions that affect how cows distribute their weight. In 3
      experiments, 10, 18, and 12 Holstein cows were trained to stand on a platform
      that measured the weight placed on each of their legs. The objectives were to
      evaluate how cows change their weight distribution after milking, after calving,
      and when standing with the front legs elevated and to evaluate the effect of the
      udder fill and fetus weight on the gait score. Comparisons before and after
      milking and before and after calving showed that the weight of milk was carried
      mainly on the back legs, whereas the weight of the fetus was distributed between
      front (52%) and back legs (48%). The percentage of weight distributed between
      front and back legs was not affected by elevation of the front legs. Weight
      shifting between contralateral legs was greater before calving than after; the
      weight variability over time decreased by 30% after calving. A full udder
      increased gait score by 0.3 +/- 0.1 and particularly abduction/adduction of the
      back legs (increased by 83%). Gait score did not change after calving, although
      the back arch increased by 25%. Therefore, time since milking and state of late
      pregnancy need consideration when using gait score and measures of weight
      distribution to detect lameness.

PMID- 19164669
TI  - Evaluation of antioxidant and proinflammatory gene expression in bovine mammary
      tissue during the periparturient period.
AB  - The incidence and severity of mastitis can be high during the period of
      transition from pregnancy to lactation when dairy cattle are susceptible to
      oxidative stress. Oxidative stress may contribute to the pathogenesis of mastitis
      by modifying the expression of proinflammatory genes. The overall goal of this
      study was to determine the relationship between critical antioxidant defense
      mechanisms and proinflammatory markers in normal bovine mammary tissue during the
      periparturient period. Mammary tissue samples were obtained from 12 cows at 35,
      20, and 7 d before expected calving and during early lactation (EL, 15 to 28 d in
      milk). Enzyme activities for cytosolic glutathione peroxidase and phospholipid
      hydroperoxide glutathione peroxidase were relatively low during the dry period,
      but increased during EL, whereas activity of thioredoxin reductase 1 did not
      change significantly as a function of time. In contrast, gene expression for
      these antioxidant selenoproteins and for heme oxygenase-1 gradually decreased as
      parturition approached and then increased during EL. The expression of
      intercellular vascular adhesion molecule-1 and vascular cell adhesion molecule-1
      followed a similar trend where mRNA abundance gradually declined as parturition
      approached with a slight rebound in EL. Gene expression of the pro-oxidant, 15
      lipoxygenase 1, which is known to increase during times of oxidative stress, also
      increased dramatically in mammary tissue from EL cows. Expression of the
      proinflammatory cytokines, IL-1beta, IL-6, and IL-8 did not change significantly
      during the periparturient period. Strong positive correlations were found between
      several antioxidant enzymes (cytosolic glutathione peroxidase, thioredoxin
      reductase 1, and heme oxygenase-1) and vascular adhesion molecules (intercellular
      vascular adhesion molecule-1, vascular cell adhesion molecule-1) suggesting a
      protective response of these antioxidants to an enhanced proinflammatory state.
      Ability to control oxidative stress through manipulation of key antioxidant
      enzymes in the future may modify the proinflammatory state of periparturient cows
      and reduce incidence and severity of some diseases such as mastitis.

PMID- 19164670
TI  - Production loss due to new subclinical mastitis in Dutch dairy cows estimated
      with a test-day model.
AB  - Milk, fat, and protein loss due to a new subclinical mastitis case may be
      economically important, and the objective of this study was to estimate this
      loss. The loss was estimated based on test-day (TD) cow records collected over a
      1-yr period from 400 randomly selected Dutch dairy herds. After exclusion of
      records from cows with clinical mastitis, the data set comprised 251,647 TD
      records from 43,462 lactations of 39,512 cows. The analysis was carried out using
      a random regression test-day modeling approach that predicts the cow production
      at each TD based on the actual production at all previous TD. The definition of
      new subclinical mastitis was based on the literature and assumed a new
      subclinical case if somatic cell count (SCC) was >100,000 cells/mL after a TD
      with SCC <50,000 cells/mL. A second data set was created by applying an
      adjustment to correct low SCC for the dilution effect when determining if the
      previous test-day SCC was <50,000 cells/ mL. Thereafter, the loss was estimated
      for records with SCC >100,000 cells/mL. The production (milk, fat, or protein)
      losses were modeled as the difference between the actual and predicted production
      (milk, fat, or protein) at the TD of new subclinical mastitis, for 4,382 cow
      records, and 2,545 cow records after dilution correction. Primiparous cows were
      predicted to lose 0.31 (0.25-0.37) and 0.28 (0.20-0.35) kg of milk/d at an SCC of
      200,000 cells/mL, for unadjusted and adjusted low SCC, respectively. For the same
      SCC increase, multiparous cows were predicted to lose 0.58 (0.54-0.62) and 0.50
      (0.44-0.56) kg of milk/d, respectively. Moreover, it was found that the greater
      the SCC increase above 100,000 cells/mL, the greater the production losses. The
      estimated production losses were more precise than previously reported estimates.

PMID- 19164671
TI  - Oligofructose overload induces lameness in cattle.
AB  - The aim was to describe the clinical orthopedic implications of oligofructose
      overload. A group of 8 nonpregnant dairy heifers were given an oral dose of
      oligofructose (17 g/kg of body weight). At predefined times during a period
      spanning 3 d before and 9 d after oligofructose overload, the heifers underwent a
      clinical examination including locomotion scoring, hoof-testing, and palpation of
      tarso-crural joints, as well as the collection of blood and ruminal fluid
      samples. Locomotion sessions were videotaped; subsequently, locomotion was blind
      scored. Locomotion scores increased after oligofructose overload and declined
      toward the end of the study period. The greatest locomotion scores were recorded
      on d 3 to 5 (60 to 120 h) where 12 of 42 (29%) locomotion scores were 3 and 13 of
      42 (32%) were score 2. Positive reactions to hoof-testing were observed from 30 h
      after oligofructose overload and reached a maximum on d 7 and 9 where 12 of 28
      (43%) reactions were marked positive. Distension of the tarso-crural joints was
      observed from 24 h after oligofructose overload, with maximum distension being
      observed on d 2, in which 44 of 56 (79%) of observed joints were either
      moderately or severely distended. The heifers developed classic signs of acute
      ruminal and systemic acidosis after the oligofructose overload (ruminal pH 4.3 +/
      0.07, standard base excess -10.8 +/- 2.3 at 18 h). With few exceptions, clinical
      and laboratory variables returned to normal within 9 d of oligofructose overload.
      But, good body condition and previous feeding with grass apparently predisposed
      the heifers to more severe systemic affection. Oligofructose overload in dairy
      heifers induced ruminal and systemic acidosis, diarrhea, dehydration, and,
      subsequently, lameness, claw pain, and joint effusion, collectively interpreted
      as signs of acute laminitis. Oligofructose overload at 17 g/kg of body weight
      represented a relatively mild laminitis model in cattle, as demonstrated by a
      reasonably quick recovery from systemic as well as orthopedic signs.

PMID- 19164672
TI  - Short communication: rising and lying behavior of heifers before and after
      alimentary oligofructose overload.
AB  - The aim of this experiment was to describe the rising and lying behavior of
      heifers in the first 5 d after alimentary oligofructose overload to 1) acquire
      information about consequences of this experimental disease model in terms of
      animal behavior; and 2) contribute to the evaluation of the influence of disease
      on cattle welfare. Eight tethered Holstein-Friesian heifers were used and their
      behavior was observed for 10.5 +/- 2.7 hours of light per day. Occurrence of
      rising and lying behavior and parts thereof were recorded. Clinical and
      physiological examinations were conducted throughout to confirm presence of
      ruminal acidosis and lameness. The duration of pre-lying intention movements were
      increased on d 3 after oligofructose overload compared with d -1 [28 (20 to 40)
      vs. 13 (10 to 16) s, respectively], and the duration of the total lying sequence
      was increased on d 1 and 3 compared with the control day [27 (22 to 33) and 36
      (25 to 48) vs. 17 (13 to 21) s, respectively]. The frequency and duration of
      getting up did not differ between days. These results suggest that disease
      induced by oligofructose overload (i.e., ruminal acidosis and lameness) can
      affect lying behavior in heifers as shown by increased duration of lying
      intentions and difficulty in lying down, which may indicate that lying motivation
      was thwarted, possibly by pain or discomfort.

PMID- 19164673
TI  - Short communication: Haptoglobin as an early indicator of metritis.
AB  - The purpose of this study was to determine whether haptoglobin (Hp) could be used
      as a predictive measure for metritis. Cattle were grouped into 3 health
      categories based on the condition of vaginal discharge and body temperature after
      calving: severe metritis (n = 12), mild metritis (n = 32), and healthy (n = 23).
      Blood was collected and analyzed for Hp concentration on d -20 +/- 5, -6 +/- 2, 
      2 +/- 1, and d 0 relative to calving, and then every 3 d after calving until d
      +21. Cows with mild and severe metritis had greater Hp concentrations than
      healthy cows between d 0 and d +12. Mean (+/-SE) Hp concentrations peaked on d +3
      in the cows with mild metritis (1.06 +/- 0.15 g/L) and on d +6 in cows with
      severe metritis (1.62 +/- 0.47 g/L). Mean concentrations for the healthy group
      were 0.58 +/- 0.12 g/L and 0.31 +/- 0.08 g/L on d +3 and d +6, respectively.
      Clinical signs of pathological discharge for the mildly and severely metritic
      cows did not occur until, on average, 8.6 +/- 3.9 d and 5.3 +/- 1.9 d after
      calving, respectively. Cows with Hp concentrations >or=1 g/L on d +3 were 6.7
      times more likely to develop severe or mild metritis; this predictive threshold
      has a sensitivity of 50% and specificity of 87%. These results indicate that an
      acute phase inflammatory response precedes clinical metritis and that Hp
      screening may assist in the early detection of metritis, providing increased
      opportunities for early treatment and prevention.

PMID- 19164674
TI  - Technical note: Flow cytometric identification of bovine milk neutrophils and
      simultaneous quantification of their viability.
AB  - The aim of the present study was to develop a flow cytometric procedure for the
      quantification of the proportion of viable, apoptotic, and necrotic
      polymorphonuclear neutrophilic leukocytes (PMNL) isolated from both low- and high
      somatic-cell-count quarter milk samples. Milk PMNL were differentiated from other
      cells by indirect fluorescent labeling using a primary anti-bovine granulocyte
      monoclonal antibody (CH138A) and an Alexa 647-labeled secondary antibody.
      Polymorphonuclear neutrophilic leukocytes were identified flow cytometrically
      based on their cytoplasmic granularity and CH138A-positivity. Additional labeling
      with annexin-V-fluorescein isothiocyanate and propidium iodide was used to
      determine milk PMNL viability. Thirty milk samples were run in parallel to assess
      the repeatability of the immunoassay and 6 repeated measurements per sample were
      performed to assess the instrument stability. Fluorescence microscopic
      verification of the CH138A staining pattern showed both a high sensitivity
      (90.9%) and specificity (92.3%). The combination of the side-scatter properties
      of granulated PMNL and CH138A-Alexa 647 positivity allows the distinction of
      labeled PMNL from other milk cells and particles that may bind nonspecifically,
      and from autofluorescent particles present in milk. Quantification of the
      proportion of PMNL and viable, apoptotic, and necrotic subpopulations in parallel
      samples gave repeatable results with concordance correlation coefficients varying
      between 0.93 and 0.99. The average coefficient of variation for repeated
      measurements in identical samples ranged between 4.2 and 9.7%. In conclusion,
      this is the first flow cytometric method suited for the simultaneous
      quantification of viable, apoptotic, and necrotic bovine milk PMNL in a
      straightforward manner.

PMID- 19164675
TI  - Technical note: Milk composition in mice--methodological aspects and effects of
      mouse strain and lactation day.
AB  - Analysis in individual mouse milk samples is restricted by small sample volumes
      and hindered by high fat contents. Miniaturized methods were developed for the
      analysis of dry matter (DM), crude fat, crude protein (CP), and lactose in
      individual samples of <or=200 microL of fresh or previously frozen mouse milk and
      used to compare milk from the mouse strain DU6, the largest growth-selected mouse
      line worldwide, with unselected mice (CON) on lactation d 3, 14, and 18.
      Individual milk samples were collected by means of a self-constructed milking
      machine. Aliquots of 10 microL of milk were used to measure DM [coefficient of
      variation (CV) <2.1%], which was subsequently used to analyze nitrogen for
      calculation of CP (CV 2.7%). Crude fat was determined in 100 microL via a
      miniaturized Rose-Gottlieb method (CV 2.8%). An HPLC protocol was used to analyze
      lactose in 20 microL of diluted whey (CV 5.3%). The miniaturized methods gave
      similar results compared with conventional approaches. Homogenization was the
      most important factor affecting milk composition and its reproducibility. Milk
      storage at -20 degrees C had no effect on composition. Irrespective of the mouse
      strain, maximum values of 45.5% DM, 29.8% fat, and 12.7% CP were observed at d
      14. The greatest lactose contents were found on d 18 (2.41%). Milk lactose
      concentration at d 3 was lower in DU6 (1.13 +/- 0.10%) than CON (1.67 +/- 0.18%).
      The method provides an accurate assessment of mouse milk composition.

PMID- 19164676
TI  - The quality of commercial wheat silages in Israel.
AB  - Wheat silages are the major roughage for high-producing lactating dairy cows in
      Israel; therefore, their quality is important. The main objective of the current
      study was to determine the preservation status and nutritional quality of
      commercial wheat silages in Israel. An additional objective was to develop
      predictive equations for dry matter digestibility (DMD) and neutral detergent
      fiber digestibility (NDFD) based on chemical composition of the silages, which
      would permit estimation of the digestibility from chemical composition. A total
      of 143 commercial wheat silages were sampled and analyzed for 3 yr. Fourteen
      random samples that were not included in the regression analysis were used to
      validate the equations by the bias and error of the model. Results revealed that
      wheat silages were quite sensitive to aerobic exposure; additives resulted in
      some improvement of the aerobic stability. After choosing the significant terms
      from ash, crude protein (CP), NDF, acid detergent fiber (ADF), and acid detergent
      lignin (ADL) by PROC STEPWISE of SAS, the following prediction equations were
      obtained from all 143 samples: DMD = 86.3 + (0. 70 x CP) - (0.46 x ADF) - (1.67 x
      ADL); and NDFD = 20.3 + (1.00 x CP) + (1.16 x NDF) - (0.88 x ADF) - (2.25 x ADL).
      The bias and the error of the prediction model for DMD were approximately 0.006
      and 0.065, respectively; the bias and error for NDFD were approximately 0.007 and
      0.118, respectively. It was concluded that the prediction model for DMD was quite
      adequate, whereas that for NDFD was less acceptable.

PMID- 19164677
TI  - Influence of weaning method on health status and rumen development in dairy
      calves.
AB  - In the artificial rearing of dairy calves, the same feeding plan is applied to
      all animals during the milk-feeding period, with individual differences
      attributable to development or health status rarely considered. The aim of this
      study was 1) to analyze whether the parameters of feeding behavior automatically
      recorded by a feeding computer and weight gain are suitable for predicting the
      health status and rumen development of male dairy calves, and 2) to compare a
      conventional weaning method (end of milk provision at 12 wk of age, n = 23
      calves) with a concentrate-dependent weaning method (with reduction in the milk
      amount depending on the consumption of concentrate, n = 24). The health status of
      each animal was evaluated daily by a scoring list (health score), and body
      temperature was measured automatically during each milk intake. In addition, the
      number of veterinary treatments per calf was recorded. Rumen development was
      assessed by measuring rumen papillae in 8 rumen areas after slaughter (n = 24,
      half of each treatment group). During the milk-feeding period, body temperature
      was elevated (>/=39.5 degrees C) on 40.8 and 43.2% of all days for calves on the
      concentrate-dependent weaning method and the conventional weaning method,
      respectively. Hay and concentrate intake (but not milk intake) and weight gain
      were clearly affected by health status. In addition, health score and the
      probability of being treated by a veterinarian were significantly related to
      decreases in concentrate consumption. During the milk-feeding period, increased
      body temperature, an increased number of veterinary treatments, and decreases in
      milk consumption were all associated with reduced weight gain. Calves on the
      concentrate-dependent weaning method were weaned at an average age of 76 d, which
      was significantly shorter than the age at the end of milk provision for
      conventionally fed calves (84 d). Weight gain and health status did not differ
      between treatment groups. Weight gain was positively associated with papillae
      length. A treatment effect on rumen development could not be found. We conclude
      that the concentrate-dependent weaning method allows a faster physiological
      development without any negative impact on rumen development, weight gain, or
      health status; we therefore recommend its use in practice.

PMID- 19164678
TI  - Effects of dietary supplemental fish oil during the peripartum period on blood
      metabolites and hepatic fatty acid compositions and total triacylglycerol
      concentrations of multiparous Holstein cows.
AB  - The objectives were to evaluate the effects of dietary fish oil on plasma
      metabolite, hepatic fatty acid composition, and total triacylglycerol
      concentrations. Multiparous Holstein cows (n = 42) were completely randomized to
      1 of 3 treatments at 3 wk prepartum. Treatments were no supplemental lipid or
      supplemental lipid from either Energy Booster (Milk Specialties Co., Dundee, IL)
      or fish oil. Treatment diets were fed from -21 d relative to expected date of
      parturition until 10 d postpartum. Treatments were fed as a bolus before the a.m.
      feeding. The dose of lipid fed during the prepartum period was 250 g, whereas
      approximately 0.92% of the previous day's dry matter intake was supplemented
      postpartum. Blood was collected 3 times weekly for determination of plasma
      metabolites. Liver biopsies were performed at 21 and 10 d before expected date of
      parturition and 1 and 14 d after parturition to determine fatty acid compositions
      and total triacylglycerol concentrations. Dry matter intake, milk yield, and loss
      of body weight or body condition score were not affected by supplementing the
      diet with lipid or by the source of lipid. Supplemental lipid tended to increase
      plasma glucose and decrease nonesterified fatty acids during the postpartum
      period. Furthermore, plasma beta-hydroxybutyrate was reduced during the
      postpartum period in the lipid-supplemented treatments. However, source of
      supplemental lipid had no influence on any blood metabolite. Supplemental fish
      oil altered the fatty acid composition of liver phospholipids and
      triacylglycerols, decreasing total saturated fatty acids and increasing total n-3
      and long-chain polyunsaturated fatty acids (>20 carbon fatty acids). Despite the
      altered fatty acid composition, hepatic total triacylglycerol concentrations were
      unaffected by supplemental fish oil. Furthermore, the improved metabolic profile
      following lipid supplementation did not decrease hepatic total triacylglycerol
      concentrations.

PMID- 19164679
TI  - Effects of changing the essential and functional fatty acid intake of dairy
      calves.
AB  - There is limited information on the effects and requirements of specific fatty
      acids for dairy calves. The starter diet based on corn and soybean meal, which is
      typical in the United States, is low in C(18:3), and the ratio of C(18:2) to
      C(18:3) is quite high relative to recommendations for human infants.
      Additionally, other functional fatty acids (C(20:4), C(20:5), C(22:6)) elongated
      from C(18:2) and C(18:3) have proven benefits in monogastric species. Thus, the
      effect of adding Ca salts of flax oil (high in C(18:3)) or fish oil (high in
      C(20:4), C(20:5), C(22:6)) to the starter diet of calves less than 3 mo old was
      investigated. In trial 1, 48 Holstein bull calves [43.2 +/- 1.4 kg of body weight
      (BW); 12/treatment] that were 2 to 3 d of age were fed 1 of 4 starter treatments
      containing A) no flax or fish oil (control), B) 0.125% Ca salt of flax oil, C)
      0.250% Ca salt of flax oil, or D) 0.250% Ca salt of fish oil. Starters and water
      were fed free-choice to calves. During the first 56 d, calves were individually
      penned. From arrival until d 28, calves were fed a 26% crude protein, 17% fat
      milk replacer. From 56 to 84 d, calves were penned in groups of 6 and maintained
      on their same starter blended with 5% chopped grass hay. Trial 2 used 96 Holstein
      steer calves (66.3 +/- 3.11 kg of BW; 24/treatment) that were 59 to 60 d old in a
      28-d trial. These calves had been managed for their first 56 d in the same way as
      the calves from trial 1 before starting trial 2. Trial 2 evaluated increasing
      concentrations of Ca salt of flax oil within a starter blended with 5% chopped
      grass hay and fed with water free-choice. The 4 treatments were A) 0%, B) 0.083%,
      C) 0.167%, and D) 0.250% Ca salt of flax oil. In trial 1, there were no
      differences among calves fed the control diet and calves fed the diet
      supplemented with flax oil. In trial 1, average daily gain (ADG) increased
      linearly as flax oil increased in the starter from d 0 to 56 and from d 56 to 84,
      and hip width change increased linearly as flax oil increased in the starter.
      Serum urea nitrogen and serum glucose concentrations decreased as flax oil
      increased in the diet. In trial 2, ADG and feed efficiency increased linearly as
      flax oil increased in the starter. Serum alkaline phosphatase concentrations
      increased as flax oil increased in the diet. Supplementing a Ca salt of fish oil
      had no effect on any variables measured. Supplementing C(18:3) (linolenic acid)
      as a Ca salt of flax oil to the corn and soybean meal-based diet of dairy calves
      less than 3 mo old resulted in increased ADG and feed efficiency.

PMID- 19164680
TI  - Effects of supplements of folic acid, vitamin B12, and rumen-protected methionine
      on whole body metabolism of methionine and glucose in lactating dairy cows.
AB  - The present experiment was undertaken to determine the effects of dietary
      supplements of rumen-protected methionine and intramuscular injections of folic
      acid and vitamin B(12), given 3 wk before to 16 wk after calving, on glucose and
      methionine metabolism of lactating dairy cows. Twenty-four multiparous Holstein
      cows were assigned to 6 blocks of 4 cows each according to their previous milk
      production. Within each block, 2 cows were fed a diet estimated to supply
      methionine as 1.83% metabolizable protein, equivalent to 76% of methionine
      requirement, whereas the 2 other cows were fed the same diet supplemented daily
      with 18 g of rumen-protected methionine. Within each diet, the cows were
      administrated either no vitamin supplement or weekly intramuscular injections of
      160 mg of folic acid plus 10 mg of vitamin B(12.) To investigate metabolic
      changes at 12 wk of lactation, glucose and methionine kinetics were measured by
      isotope dilution using infusions of 3[U-(13)C]glucose, [(13)C]NaHCO(3) and 3[1
      (13)C,(2)H(3)] methionine. Milk and plasma concentrations of folic acid and
      vitamin B(12) increased with vitamin injections. Supplementary B-vitamins
      increased milk production from 34.7 to 38.9 +/- 1.0 kg/d and increased milk
      lactose, protein, and total solids yields. Whole-body glucose flux tended to
      increase with vitamin supplementation with a similar quantitative magnitude as
      the milk lactose yield increase. Vitamin supplementation increased methionine
      utilization for protein synthesis through increased protein turnover when
      methionine was deficient and through decreased methionine oxidation when rumen
      protected methionine was fed. Vitamin supplementation decreased plasma
      concentrations of homocysteine independently of rumen-protected methionine
      feeding, although no effect of vitamin supplementation was measured on methionine
      remethylation, but this could be due to the limitation of the technique used.
      Therefore, the effects of these B-vitamins on lactation performance were not
      mainly explained by methionine economy because of a more efficient
      methylneogenesis but were rather related to increased glucose availability and
      changes in methionine metabolism.

PMID- 19164681
TI  - Effect of applying molasses or inoculants containing homofermentative or
      heterofermentative bacteria at two rates on the fermentation and aerobic
      stability of corn silage.
AB  - This study determined how the fermentation and aerobic stability of corn silage
      are affected by treatment with molasses or 2 dual-purpose inoculants applied at
      or above the recommended rate. Corn forage (DeKalb 69-70) was harvested at 39%
      dry matter (DM) and ensiled after treatment with no additives (control, CON),
      molasses (MOL), Buchneri 500 inoculant, or Pioneer 11C33 inoculant. Molasses was
      applied at 3% of forage DM. Buchneri 500 was applied at the recommended rate of 8
      mg/kg fresh forage to supply 1 x 10(5) cfu/g of Pediococcus pentosaceus 12455 and
      4 x 10(5) cfu/g of Lactobacillus buchneri 40788 (BB) or at twice the recommended
      rate (DBB). Pioneer 11C33 inoculant was applied at the recommended rate of 1.1
      mg/kg fresh forage to supply 1 x 10(5) cfu/g of a mixture of Lactobacillus
      plantarum, L. buchneri, and Enteroccocus faecium (PN) or at twice the recommended
      rate (DPN). Each treatment was applied in quadruplicate and the treated forages
      were ensiled within 20-L mini silos for 135 d at 18 to 35 degrees C. Molasses
      treated silages had greater ash and starch concentrations than CON silages and
      greater lactate and ethanol concentrations than other silages. Like CON silages,
      MOL silages had high yeast counts (>10(5) cfu/g); consequently, they deteriorated
      within 30 h as shown by temperature increase. Inoculant-treated silages had lower
      lactate to acetate ratios than CON or MOL silages largely because they had
      greater acetate concentrations. Consequently, all inoculant-treated silages had
      fewer yeasts (<10(5) cfu/g) and were more stable (>30 h) than CON and MOL
      silages. When applied at recommended rates, PN and BB had similar effects on
      silage chemical composition, fermentation, fungal counts, and aerobic stability,
      except for a lower lactate concentration in PN silages. Concentrations of VFA,
      and NH(3)-N, pH, and extent of aerobic stability were similar for PN, DPN, BB,
      and DBB silages. However, lactate concentration was greater in DPN than in PN. In
      conclusion, MOL application increased ethanol and lactate concentration and did
      not improve aerobic stability. Both dual-purpose inoculants made the fermentation
      more heterolactic and thereby improved the aerobic stability of corn silage.
      Doubling the rate of application of either inoculant did not further improve
      fermentation or aerobic stability.

PMID- 19164682
TI  - Effects of supplementing glycerol and soybean oil in drinking water on feed and
      water intake, energy balance, and production performance of periparturient dairy
      cows.
AB  - The objective of this study was to determine the effects of supplementing
      glycerol and soybean oil in drinking water on feed and water intake, calculated
      energy balance, and production performance of periparturient dairy cows. Ninety
      multiparous Holstein dairy cows were randomly assigned to 1 of 3 treatments: 1)
      no nutrients supplemented in the drinking water (control); 2) 20 g/L of glycerin
      supplemented in the drinking water (glycerol); and 3) 10 g/L of soybean oil
      supplemented in the drinking water (SBO). The trial lasted from 7 d prepartum to
      7 d postpartum. Cows were offered a close-up and milking cow TMR for ad libitum
      intake, pre- and postpartum, respectively. The dry matter intake of cows
      supplemented with glycerol and SBO was lower than for the control cows throughout
      the experimental period but not different from each other. Water intake for the
      control cows was greater than the average for the glycerol and SBO cows
      prepartum, and greater than for SBO cows but similar to that of glycerol cows
      postpartum. Glycerol cows consumed more water than SBO cows. There were no
      differences in energy intake and energy balance of the cows pre- and postpartum.
      Serum triacylglycerol concentration for glycerol cows was lower than for the
      control and SBO cows prepartum and was lower than for the SBO cows postpartum.
      There were no differences in the serum nonesterified fatty acids and glucose
      concentrations throughout the experiment. There were no differences in the serum
      beta-hydroxybutyrate (BHBA) concentrations at parturition, but serum BHBA
      concentration of the glycerol cows was greater than for control and SBO cows
      during the prepartum period. However, during the postpartum period, serum BHBA
      concentrations of the control cows were greater than for glycerol and SBO cows.
      There were no differences in calf birth weights or milk yield and composition.
      Although the glucogenic property of glycerol supplemented in the drinking water
      at 20 g/L may not have been sufficient to elicit a milk yield response, it did
      reduce the concentration of BHBA postpartum.

PMID- 19164683
TI  - Evaluating estimates of phosphorus maintenance requirement of lactating Holstein
      cows with different dry matter intakes.
AB  - The objective was to evaluate estimates of the inevitable fecal loss component of
      the P maintenance requirement of lactating Holstein cows consuming differing
      amounts of a low-P diet. The maintenance requirement for P is the sum of
      inevitable (e.g., unavoidable) endogenous fecal P plus endogenous urinary P when
      an animal is fed near its true P requirement (i.e., zero P balance). Urinary
      excretion of P is normally very low in healthy cattle. Inevitable fecal P is the
      main part of the total P maintenance requirement; it can be expressed as grams of
      fecal P/kilogram of dry matter intake (DMI). Twenty-one multiparous lactating
      Holstein cows (55 to 253 +/- 6 d in milk, range +/- SD; 0 to 171 +/- 64 d
      pregnant) with a wide range of pretrial milk yields (25.3 to 47.3 +/- 1.23 kg/cow
      per day) were selected to achieve a range in DMI and assigned to treatment groups
      of low, medium, and high DMI. To obtain an even greater range in DMI, rations fed
      to cows in the low and medium treatment groups were restricted to 75 and 50% of
      their pretrial ad libitum intakes, respectively. Dry matter intakes during the
      experiment averaged 11.3 (low), 15.3 (medium), and 25.1 (high) kg/cow per d,
      respectively. All cows were fed the same low-P diet (0.26% P, dry basis)
      throughout the experiment. Phosphorus balances of cows in all treatments were not
      different from zero and unaffected by DMI. Average daily total inevitable fecal P
      excretion was 15.3, 18.2, and 26.3 g/cow for low, medium, and high DMI,
      respectively. Inevitable fecal P excretion was 1.36, 1.19, and 1.04 g/kg of DMI
      for low, medium, and high and decreased linearly with increasing DMI. The
      regression equation to estimate inevitable fecal P excretion across the range of
      DMI was: (g/d) = [0.85 +/- 0.070 (g/d)] x DMI (kg/d) + [5.30 +/- 1.224 (g/d)];
      (R(2) = 0.90). This equation can be used to estimate the inevitable fecal P
      component of the total P maintenance requirement of lactating Holstein cows.

PMID- 19164684
TI  - Relative bioavailability of all-rac and RRR vitamin E based on neutrophil
      function and total alpha-tocopherol and isomer concentrations in periparturient
      dairy cows and their calves.
AB  - The objective of this experiment was to determine whether source of supplemental
      alpha-tocopherol fed to periparturient dairy cows affects neutrophil function and
      vitamin E status of the cow and the neonatal calf. Starting 14 d before
      anticipated calving and continuing until 14 d post-parturition, cows were fed
      diets with no supplemental vitamin E or with 2,500 IU/d of vitamin E from all-rac
      alpha-tocopheryl acetate or RRR alpha-tocopheryl acetate. All-rac alpha
      tocopherol contains equimolar amounts of all 8 stereoisomers, whereas the RRR
      contains only the RRR isomer. Concentrations of alpha-tocopherol in cow plasma,
      colostrum, milk, and blood neutrophils were greatest for the RRR treatment,
      intermediate for all-rac, and lowest for cows fed no supplemental vitamin E. The
      concentration of alpha-tocopherol in plasma of newborn calves was very low and
      not affected by treatment but after 6 feedings of their dam's colostrum or milk,
      concentrations in calf plasma followed the same treatment pattern as cow plasma.
      The number of bacteria phagocytized was greater by neutrophils from cows fed all
      rac vitamin E than for the other 2 treatments, which resulted in a greater number
      of bacteria being killed. For cows fed all-rac vitamin E, the RRR isomer
      comprised about 20% of the alpha-tocopherol consumed but approximately 60% of the
      alpha-tocopherol in plasma and milk. This enrichment was caused mostly by an
      almost complete discrimination against the 2S isomers. Because all-rac alpha
      tocopherol is 50% 2S isomers, these data suggest that 1 g of all-rac tocopheryl
      acetate is equivalent to 0.5 g of RRR tocopheryl acetate.

PMID- 19164685
TI  - Effects of an esterase-producing inoculant on fermentation, aerobic stability,
      and neutral detergent fiber digestibility of corn silage.
AB  - This experiment evaluated effects of an inoculant containing esterase-producing
      bacteria on fermentation, aerobic stability, in situ dry matter digestibility
      (DMD), and neutral detergent fiber (NDF) digestibility (NDFD) of corn silage. Two
      corn hybrids grown on adjacent fields [Croplan Genetics 851RR2 (CS1) and Vigoro
      61R36 (CS2)] were harvested at approximately 39% dry matter. Each forage was
      conserved in quadruplicate in 20-L mini silos with or without application of an
      inoculant at a level to achieve 1.0 x 10(4) cfu/g of Lactobacillus casei and 1.0
      x 10(5) cfu/g of Lactobacillus buchneri. After 110 d of ensiling, silos were
      opened and silages were analyzed for chemical composition, fermentation indices,
      microbial counts, and aerobic stability. In situ DMD, 24-h and 48-h DMD, and NDFD
      were measured by incubating ground (6-mm) samples in triplicate in each of 2
      lactating, fistulated dairy cows fed a corn silage-based diet. Inoculation
      decreased concentrations of total fermentation acids and lactate, as well as
      lactate to acetate ratio, and increased propionate concentration compared with
      the uninoculated control in CS1 but not CS2. Inoculation tended to decrease yeast
      counts of CS1 but increased yeast counts and tended to increase the mold counts
      of CS2. Consequently, inoculation improved the aerobic stability of CS1 by 57.3 h
      (98%) but decreased that of CS2 by 20.5 h (20%). Inoculation also increased the
      potentially degradable fraction of CS1 and the total degradable fraction, 24-h
      and 48-h DMD, and 48-h NDFD of CS2. Inoculation of CS1 modified the fermentation,
      improved the aerobic stability, and increased the potentially degradable DM
      fraction. Inoculation of CS2 did not affect fermentation, but decreased the
      aerobic stability and increased the total degradable DM fraction, 24-h and 48-h
      DMD, and 48-h NDFD.

PMID- 19164686
TI  - Assessment of Poisson, logit, and linear models for genetic analysis of clinical
      mastitis in Norwegian Red cows.
AB  - Clinical mastitis is typically coded as presence/absence during some period of
      exposure, and records are analyzed with linear or binary data models. Because
      presence includes cows with multiple episodes, there is loss of information when
      a count is treated as a binary response. The Poisson model is designed for
      counting random variables, and although it is used extensively in epidemiology of
      mastitis, it has rarely been used for studying the genetics of mastitis. Many
      models have been proposed for genetic analysis of mastitis, but they have not
      been formally compared. The main goal of this study was to compare linear
      (Gaussian), Bernoulli (with logit link), and Poisson models for the purpose of
      genetic evaluation of sires for mastitis in dairy cattle. The response variables
      were clinical mastitis (CM; 0, 1) and number of CM cases (NCM; 0, 1, 2, ..). Data
      consisted of records on 36,178 first-lactation daughters of 245 Norwegian Red
      sires distributed over 5,286 herds. Predictive ability of models was assessed via
      a 3-fold cross-validation using mean squared error of prediction (MSEP) as the
      end-point. Between-sire variance estimates for NCM were 0.065 in Poisson and
      0.007 in the linear model. For CM the between-sire variance was 0.093 in logit
      and 0.003 in the linear model. The ratio between herd and sire variances for the
      models with NCM response was 4.6 and 3.5 for Poisson and linear, respectively,
      and for model for CM was 3.7 in both logit and linear models. The MSEP for all
      cows was similar. However, within healthy animals, MSEP was 0.085 (Poisson),
      0.090 (linear for NCM), 0.053 (logit), and 0.056 (linear for CM). For mastitic
      animals the MSEP values were 1.206 (Poisson), 1.185 (linear for NCM response),
      1.333 (logit), and 1.319 (linear for CM response). The models for count variables
      had a better performance when predicting diseased animals and also had a similar
      performance between them. Logit and linear models for CM had better predictive
      ability for healthy cows and had a similar performance between them.

PMID- 19164687
TI  - Differences in udder health and immune response traits of Holstein-Friesians,
      Norwegian Reds, and their crosses in second lactation.
AB  - The objective of this study was to investigate potential differences in udder
      health and immune response traits among Holstein-Friesian (HF), Norwegian Red
      (NR), and NR x HF (NRX) cows on 30 commercial Irish dairy farms. A total of 648
      second-lactation cows (HF n = 274, NR n = 207, and NRX n = 167) were immunized
      with hen egg white lysozyme (HEWL) to induce antibody-mediated immune response
      (AMIR). Candida albicans was used to induce a cell-mediated immune response, with
      in vivo delayed-type hypersensitivity used as the indicator. Antibody response to
      HEWL was measured by ELISA. Udder health defined as mean somatic cell score (SCS)
      over the lactation, mean SCS within 30 d of the beginning of the immunization,
      peak SCS for each individual cow during lactation, and incidence of mastitis were
      statistically superior for the NR. The NR had a greater primary AMIR, producing
      greater concentrations of anti-HEWL immunoglobulin G on d 14 compared with HF and
      NRX. No difference was observed among the breed groups in the magnitude of
      secondary AMIR (d 21 post-immunization) or cell-mediated immune response. The
      proportion of high and low responders was similar across breed groups. Cows with
      high AMIR and high cell-mediated immune response had significantly lower mean SCS
      within 30 d of the start of the immunization, but greater occurrence of clinical
      mastitis, recorded as a binary trait over the course of the lactation. Otherwise,
      no significant difference in udder health was evident between cows designated as
      high and low responders. Although differences in mean breed group SCS values were
      in line with group mean AMIR values, no association was found among the traits
      when correlated on an individual cow basis. Results highlight the superiority of
      the NR with regard to udder health and suggest that improvements to udder health
      may result from crossbreeding with the NR. However, the immune response traits
      investigated proved to be inconsistent indicators of udder health.

PMID- 19164688
TI  - Fine mapping and association analysis of a quantitative trait locus for milk
      production traits on Bos taurus autosome 4.
AB  - To fine map a quantitative trait locus (QTL) affecting milk production traits
      previously associated with microsatellite RM188, we implemented an interval
      mapping analysis by using microsatellite markers in a large Israeli Holstein half
      sib sire family, and linkage disequilibrium (LD) mapping in a large set of US
      Holstein bulls. Interval mapping located the target QTL to the near vicinity of
      RM188. For the LD mapping, we identified 42 single nucleotide polymorphisms (SNP)
      in 15 genes in a 12-Mb region on bovine chromosome 4. A total of 24 tag SNP were
      genotyped in 882 bulls belonging to the University of California Davis archival
      collection of Holstein bull DNA samples with predicted transmitted ability
      phenotypes. Marker-to-marker LD analysis revealed 2 LD blocks, with intrablock
      r(2) values of 0.10 and 0.46, respectively; outside the blocks, r(2) values
      ranged from 0.002 to 0.23. A standard additive/dominance model using the
      generalized linear model procedure of SAS and the regression module of HelixTree
      software were used to test marker-trait associations. Single nucleotide
      polymorphism 9 on ARL4A, SNP10 on XR_027435.1, SNP12 on ETV1, SNP21 on SNX13, and
      SNP24 were significantly associated with milk production traits. We propose the
      interval encompassing ARL4A and SNX13 genes as a candidate region in bovine
      chromosome 4 for a concordant QTL related to milk protein traits in dairy cattle.
      Functional studies are needed to confirm this result.

PMID- 19164689
TI  - Impacts of using inbred animals in studies for detection of quantitative trait
      loci.
AB  - Effects of utilizing inbred and noninbred family structures in experiments for
      detection of quantitative trait loci (QTL) were compared in this simulation
      study. Simulations were based on a general pedigree design originating from 2
      unrelated sires. A variance component approach of mapping QTL was applied to
      simulated data that reflected common family structures from dairy populations.
      Five different family structures were considered: FS0 without inbreeding, FS1
      with an inbred sire from an aunt-nephew mating, FS2 with an inbred sire
      originating from a half-sib mating, FS3 and FS4 based on FS2 but containing an
      increased number of offspring of the inbred sire (FS3), and another extremely
      inbred sire with its final offspring (FS4). Sixty replicates each of the 5 family
      structures in 2 simulation scenarios each were analyzed to provide a praxis-like
      situation of QTL analysis. The largest proportion of QTL position estimates
      within the correct interval of 3 cM, best test statistic profiles and the
      smallest average bias were obtained from the pedigrees described by FS4 and FS2.
      The approach does not depend on the kind and number of genetic markers.
      Inbreeding is not a recommended practice for commercial dairy production because
      of possible inbreeding depression, but inbred animals and their offspring that
      already exist could be advantageous for QTL mapping, because of reduced genetic
      variance in inbred parents.

PMID- 19164690
TI  - Technical note: A new and cost-effective method for detection of the bovine acyl
      CoA:diacylglycerol acyltransferase 1 K232A polymorphism in cattle.
AB  - A new, quick, and inexpensive method for detecting the bovine acyl
      CoA:diacylglycerol acyltransferase1 (DGAT1) polymorphism (K232A) through tetra
      primer amplification refractory mutation system by PCR (ARMS-PCR) was developed
      in the present investigation. The DGAT1 gene was recently identified as
      underlying variation in milk production traits. To date, PCR techniques such as
      PCR-RFLP have been used for detecting the DGAT1 K232A polymorphism, despite being
      expensive and laborious. The method proposed here, a tetra-primer ARMS-PCR,
      showed 100% sensitivity and specificity when compared with PCR-RFLP results
      obtained in a sample of 80 animals tested in a double-blind system. Our results
      suggest that the use of tetra-primer ARMS-PCR for DGAT1 K232A polymorphism
      genotyping could greatly reduce costs providing information for both research
      purposes and for dairy cattle breeders who perform DGAT1 genotyping for gene
      assisted selection.

PMID- 19164691
TI  - A randomized herd-level field study of dietary interactions with monensin on milk
      fat percentage in dairy cows.
AB  - This field trial evaluated the effects of dietary supplementation with 16 mg/kg
      (based on total dry matter intake) of monensin sodium on bulk tank milk fat
      percentage (MFP) of commercial dairy herds. Interactions between monensin and
      nutritional factors on MFP were studied. The trial was conducted in 47 Holstein
      dairy herds in Quebec, Canada, between November 2005 and May 2006. The herd was
      the unit of interest. Enrolled herds were followed for a 7-mo period. Monensin
      treatment was randomly allocated in a crossover design where monensin was
      supplemented to the lactating dairy cow diet for a consecutive 12-wk period.
      Twenty-four herds were allocated to monensin treatment for the first period of
      trial, and 23 herds were allocated for the second period. Diet composition and
      ration physically effective particle level were collected every 8 wk. Milk fat
      percentage data were retrieved from weekly bulk tank measures. Data were analyzed
      in linear mixed models using repeated measures within herd where MFP was
      considered the outcome variable. In addition to the main effect of monensin
      treatment, the following covariates were forced a priori into all statistical
      models: treatment period, weekly herd mean parity, and weekly herd mean days in
      milk. The majority of herds were fed a total mixed ration (n = 29) and were
      housed in tie-stalls (n = 42). Monensin significantly decreased bulk tank MFP by
      0.12 percentage points. The reduction of MFP associated with monensin was larger
      for herds having a diet high (>39.7%) in nonfiber carbohydrates, having a low
      level of physically effective particles in ration (>45.0%; >or=8 mm), and not
      feeding dry hay as first meal in the morning. Significant interactions between
      monensin and nutritional factors on bulk tank MFP were related to nonfiber
      carbohydrate and fiber concentrations in the diet.

PMID- 19164692
TI  - Effects of corn processing, particle size, and diet form on performance of calves
      in bedded pens.
AB  - In a series of 5 trials, Holstein calves from zero to 12 wk old were housed in
      pens bedded with straw and fed diets to evaluate physical form of starters
      containing different processed corn on calf performance. Starters were formulated
      to have similar ingredient and nutrient compositions. Calves, initially less than
      1 wk old, were housed in individual pens through 8 wk and weaned at 6 wk in trial
      1 and at 4 wk in trials 2 and 3. In trials 4 and 5, calves initially 8 wk old
      were housed in group pens (6 calves/pen) from 8 to 12 wk. Trial 1 compared
      feeding calves a pelleted versus textured starter. Trial 2 compared feeding
      calves a textured starter versus feeding half meal starter with half textured
      starter. Trial 3 compared feeding calves textured starters containing whole,
      steam-flaked, or dry rolled corn. Trial 4 compared feeding calves textured
      starters containing steam-flaked versus dry rolled corn. Trial 5 compared feeding
      calves textured starters containing whole or dry rolled corn. Measurements
      included average daily gain (ADG), starter intake, feed efficiency, hip width
      change, body condition score change, fecal scores, and medical treatments.
      Physical form of starter feed did not affect any measurements in trials 1, 3, 4,
      and 5. In trial 2, calves fed starters manufactured with large amounts of fines
      had 11% less feed intake and 6% slower ADG than calves fed a textured starter.
      When starters contained similar ingredient and nutrient contents, manufacturing
      processes did not affect calf performance unless the diet contained a significant
      amount of fines, which reduced intake and ADG.

PMID- 19164693
TI  - The addition of cottonseed hulls to the starter and supplementation of live yeast
      or mannanoligosaccharide in the milk for young calves.
AB  - The objectives of this study were to investigate the effects of the addition of
      cottonseed hulls (CSH) to the starter and the supplementation of live yeast
      product (YST) or mannanoligosaccharide product (MOS) to milk, on growth, intake,
      rumen development, and health parameters in young calves. Holstein (n = 116) and
      Jersey (n = 46) bull (n = 74) and heifer (n = 88) calves were assigned randomly
      within sex at birth to treatments. All calves were fed 3.8 L of colostrum daily
      for the first 2 d. Holstein calves were fed 3.8 L of whole milk, and Jersey
      calves were fed 2.8 L of whole milk through weaning at 42 d. Calves continued on
      trial through 63 d. Six treatments were arranged as a 2 x 3 factorial. Calves
      received either a corn-soybean meal-based starter (21% crude protein and 6% acid
      detergent fiber; -CSH) or a blend of 85% corn-soybean meal-based starter and 15%
      CSH (18% crude protein and 14% acid detergent fiber; +CSH) ad libitum. In
      addition, calves received whole milk with either no supplement (NONE) or
      supplemented with 3 g/d of mannanoligosaccharide product (MOS) or 4 g/d of live
      yeast product (YST) through weaning at 42 d. Twelve Holstein steers [n = 6 (per
      starter type); n = 4 (per supplement type)] were euthanized for collection and
      examination of rumen tissue samples. Dry matter intake (DMI) was greater for
      Holstein calves fed +CSH (0.90 kg/d) than -CSH (0.76 kg/d). Final body weight at
      63 d of Holstein calves fed +CSH (75.8 kg) was greater than that of those fed 
      CSH (71.0 kg). Average daily gain (ADG) was greater for Holstein calves fed +CSH
      (0.58 kg/d) than -CSH (0.52 kg/d). However, Holstein calves fed -CSH had a
      greater feed efficiency (FE; 0.71 kg of ADG/kg of DMI) than those fed +CSH (0.65
      kg of ADG/kg of DMI). Also, Holstein calves fed +CSH had narrower rumen papillae
      (0.32 mm) compared with those fed -CSH (0.41 mm). There were no significant
      effects of CSH on DMI, ADG, or FE in Jersey calves. There were no significant
      effects of YST or MOS on DMI, ADG, FE, or rumen papillae measures in Holstein
      calves. Jersey calves fed YST or MOS had greater final body weight at 63 d (51.2
      kg and 51.0 kg, respectively) than calves fed NONE (47.5 kg). However, there were
      no significant effects of YST or MOS on DMI, ADG, or FE in Jersey calves.

PMID- 19164694
TI  - Impact of conventional or intensive milk replacer programs on Holstein heifer
      performance through six months of age and during first lactation.
AB  - The objectives were to evaluate the impact of conventional or intensive milk
      replacer (MR) feeding programs on heifer calf performance through 6 mo of age,
      age at first calving, and first lactation performance. At 3 (+/-1 d) d of age,
      133 Holstein heifer calves from 3 commercial dairy farms were randomly assigned,
      within calf source, to a conventional [20% crude protein (CP), 20% fat] or
      intensive MR (28% CP, 18% fat). Milk replacer treatments and percent solids were
      1) conventional nonacidified (CNA), 13.9%; 2) conventional acidified (CA), 13.9%;
      3) modified intensive high solids (IHS), 16.7%; 4) modified intensive low solids
      (ILS), 12.5%; and 5) intensive high solids, high feeding (IHSHF), 16.7%. Calves
      were individually housed and remained on trial for 56 d. At 2 mo of age, heifers
      were grouped in pens by treatment with 6 heifers per pen (4 pens per treatment).
      An 18.1% CP grower concentrate mix (dry matter basis) was fed to heifers that
      received a conventional MR and a 21.2% CP grower concentrate mix was fed to
      heifers that received the intensive MR preweaning. Heifers were offered 2.45 kg/d
      (dry matter basis) of their respective grower concentrate mix for 112 d plus free
      access to hay and water. At approximately 24 wk of age, heifers were transported
      to a second-stage grower before returning to their respective farms approximately
      1 mo before calving. First-lactation performance was determined using Dairy Herd
      Improvement Association records. The IHSHF treatment resulted in increased calf
      body weight and hip height during the preweaning and early postweaning (PEP)
      period and the postweaning heifer grower (PHG) period as compared with the
      conventional (CNA and CA) or modified intensive MR treatments (IHS and ILS).
      Calves receiving the IHS treatment were heavier at d 56 of the PEP period
      compared with the conventional or ILS treatments; however, this growth advantage
      was not maintained in the PHG period. Feed cost per kilogram of gain during the
      PEP period was lowest for CNA and CA, intermediate for IHS and ILS, and highest
      for the IHSHF treatment. There was no effect of MR feeding program on first
      lactation performance; however, heifers that received the IHSHF MR preweaning
      calved 27.5 d earlier than those fed a conventional MR.

PMID- 19164695
TI  - Colorectal cancer: texture analysis of portal phase hepatic CT images as a
      potential marker of survival.
AB  - PURPOSE: To assess the utility of texture analysis of liver computed tomographic
      (CT) images by determining the effect of acquisition parameters on texture and by
      comparing the abilities of texture analysis and hepatic perfusion CT to help
      predict survival for patients with colorectal cancer. MATERIALS AND METHODS: The
      study comprised a phantom test and a clinical evaluation of 48 patients with
      colorectal cancer who had consented to retrospective analysis of hepatic
      perfusion CT data acquired during a research study approved by the institutional
      review board. Both components involved texture analysis to quantify the relative
      contribution of CT features between 2 and 12 pixels wide to overall image
      brightness and uniformity. The effect of acquisition factors on texture was
      assessed on CT images of a cylindric phantom filled with water obtained by using
      tube currents between 100 and 250 mAs and voltages between 80 and 140 kVp.
      Texture on apparently normal portal phase CT images of the liver and hepatic
      perfusion parameters were related to patient survival by using Kaplan-Meier
      survival analysis. RESULTS: A texture parameter that compared the uniformity of
      distribution of CT image features 10 and 12 pixels wide exhibited the least
      variability with CT acquisition parameters (maximum coefficient of variation,
      2.6%) and was the best predictor of patient survival (P < .005). There was no
      significant association between survival and hepatic perfusion parameters.
      CONCLUSION: The study provides preliminary evidence that analysis of liver
      texture on portal phase CT images is potentially a superior predictor of survival
      for patients with colorectal cancer than CT perfusion imaging. SUPPLEMENTAL
      MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2502071879/DC1.

PMID- 19164696
TI  - Pulmonary vein imaging with unenhanced three-dimensional balanced steady-state
      free precession MR angiography: initial clinical evaluation.
AB  - PURPOSE: To determine whether unenhanced magnetic resonance (MR) angiography
      performed with a three-dimensional (3D) segmented steady-state free precession
      (SSFP) sequence would be an alternative to contrast material-enhanced MR
      angiography for evaluating pulmonary veins (PVs) prior to and following
      radiofrequency (RF) ablation for atrial fibrillation. MATERIALS AND METHODS: MR
      angiographic examinations of PVs, performed in 20 patients (nine men, 11 women;
      mean age, 56.4 years +/- 12.7 [standard deviation]), were retrospectively
      reviewed according to an institutional review board-approved protocol. The number
      of PVs and their orthogonal measurements obtained from the 3D SSFP images were
      compared with those obtained from contrast-enhanced MR angiography. Signal-to
      noise and contrast-to-noise ratios were also compared. Qualitative assessment of
      both techniques was performed by independent reviewers who scored the image
      quality (on a scale of 1 to 5) on the basis of PV conspicuity. The presence of
      cardiac and extracardiac pathologic indicators was also determined. Bland-Altman
      and Wilcoxon signed rank statistical analyses were performed. RESULTS: The mean
      difference in PV diameter measurements between contrast-enhanced MR angiography
      and 3D SSFP was -0.02 cm +/- 0.25. Signal-to-noise and contrast-to-noise ratios
      were higher for 3D SSFP images than for contrast-enhanced MR angiograms.
      Qualitatively, there was no significant difference in PV conspicuity between the
      techniques. Noncardiac pathologic indicators were detected in 10 of 20 patients
      on 3D SSFP images but not on contrast-enhanced MR angiograms. CONCLUSION:
      Unenhanced PV MR angiography performed by using a free-breathing 3D SSFP
      technique is as accurate as contrast-enhanced MR angiography for measuring PV
      diameter. This technique can be used for patients in whom contrast-enhanced
      computed tomographic or MR angiography is contraindicated and may be sufficient
      in all patients.

PMID- 19164697
TI  - Focal hepatic lesions: US-guided biopsy--lessons from review of cytologic and
      pathologic examination results.
AB  - PURPOSE: To retrospectively assess factors affecting the success of
      ultrasonographically (US)-guided core liver biopsy of focal lesions on the basis
      of experience when both cytologic and pathologic examination results were
      available. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was
      granted an exemption from the institutional review board. All percutaneous US
      guided biopsies of focal liver lesions performed at one institution from January
      2000 through February 2006 for which both cytologic and pathologic examination
      results were available were included. Specimen adequacy was determined with on
      site cytologic examination performed with a "touch prep" technique. Of 1910 liver
      biopsies, 240 (12.6%) revealed focal lesions, and cytologic and pathologic
      examination results were available for 208 (86.7%) of these 240 lesions. The
      number of biopsy passes and concordance between cytologic and pathologic findings
      were evaluated, and correlation between lesion size, type, and location and the
      number of passes was assessed. The Pearson correlation chi(2) test and the
      Wilcoxon test were used. RESULTS: Biopsy specimens were diagnostic in 205 cases
      (98.6%) and were nondiagnostic in three cases (1.4%); 85.9% of the lesions were
      malignant. There was a single lesion in 89 patients (42.8%), and there were
      multiple lesions in 119 patients (57.2%). One biopsy pass was sufficient in 58
      patients (27.9%); two passes were sufficient in 75 patients (36.1%); and three,
      four, five, and six passes were sufficient in 51 (24.5%), 17 (8.2%), five (2.4%),
      and two (1.0%) patients, respectively. There was no relationship between lesion
      size or location and the number of passes, according to the Pearson correlation
      and chi(2) test (P = .16 and P = .22, respectively). On average, 1.9 passes were
      required for metastatic lesions, versus 2.8 for nonmetastatic lesions (P < .001,
      Wilcoxon test). Cytologic and histopathologic findings were discordant in 25
      cases (12.0%). CONCLUSION: The size and location of liver lesions sampled for
      biopsy do not influence the number of passes needed, while metastatic lesions
      require fewer passes. Without the on-site cytologic examination service, a
      predetermined number of three passes would be diagnostic in almost 90% of all
      cases.

PMID- 19164698
TI  - Assessment of microvascular obstruction and prediction of short-term remodeling
      after acute myocardial infarction: cardiac MR imaging study.
AB  - PURPOSE: To evaluate which cardiac magnetic resonance (MR) imaging technique for
      detection of microvascular obstruction (MVO) best predicts left ventricular (LV)
      remodeling after acute myocardial infarction (MI). MATERIALS AND METHODS: This
      study had local ethics committee approval; all patients gave written informed
      consent. Sixty-three patients with first acute MI, treated with primary stent
      placement and optimal medical therapy, underwent cine MR imaging at 4-7 days and
      at 4 months after MI. Presence of MVO was qualitatively evaluated at baseline by
      using three techniques: (a) a single-shot saturation-recovery gradient-echo first
      pass perfusion sequence (early hypoenhancement), mean time, 1.09 minutes +/- 0.07
      (standard deviation) after contrast material administration; (b) a three
      dimensional segmented saturation-recovery gradient-echo sequence (intermediate
      hypoenhancement), mean time, 2.17 minutes +/- 0.26; and (c) a two-dimensional
      segmented inversion-recovery gradient-echo late gadolinium enhancement sequence
      (late hypoenhancement), mean time, 13.32 minutes +/- 1.26. Contrast-to-noise
      ratios (CNRs) were calculated from the signal-to-noise ratios of the infarcted
      myocardium and MVO areas. Univariable linear regression analysis was used to
      identify the predictive value of each MR imaging technique. RESULTS: Early
      hypoenhancement was detected in 44 (70%) of 63 patients; intermediate
      hypoenhancement, in 39 (62%); and late hypoenhancement, in 37 (59%). Late
      hypoenhancement was the strongest predictor of change in LV end-diastolic and end
      systolic volumes over time (beta = 14.3, r = 0.40, P = .001 and beta = 11.3, r =
      0.44, P < .001, respectively), whereas intermediate and late hypoenhancement had
      comparable predictive values of change in LV ejection fraction (beta = -3.1, r = 
      0.29, P = .02 and beta = -2.8, r = -0.27, P = .04, respectively). CNR corrected
      for spatial resolution was significantly superior for late enhancement compared
      with the other sequences (P < .001). CONCLUSION: By using cardiac MR imaging,
      late hypoenhancement is the best prognostic marker of LV remodeling, with highest
      CNR between the infarcted myocardium and MVO regions.

PMID- 19164699
TI  - Fatty hepatocellular carcinoma: radiofrequency ablation--imaging findings.
AB  - PURPOSE: To describe the imaging features during follow-up after radiofrequency
      (RF) ablation of fat-containing hepatocellular carcinoma (HCC). MATERIALS AND
      METHODS: Institutional review board approval was obtained; informed consent was
      waived. A retrospective search in an electronic radiologic archive was performed
      for a 40-month period between February 2004 and May 2007 to identify patients who
      had undergone RF ablation of fat-containing HCCs. The presence of intratumoral
      fat was determined at imaging (magnetic resonance or computed tomography) prior
      to the RF procedure; eight fat-containing HCCs, which had a mean size of 25 mm
      (range, 20-30 mm), were found. Images during follow-up were reviewed and compared
      with images prior to RF ablation to determine changes in fat content, complete or
      partial ablation, and local tumor progression. Tumor response was on the basis of
      assessment of lesion characteristics and enhancement for a follow-up of at least
      6 months. RESULTS: Persistent fat content was found at imaging in all ablation
      zones. Six patients were considered to have completely ablated tumors (mean
      follow-up, 16 months; range, 6-29 months), and two patients had local progression
      (mean follow-up, 18 months; range, 14-22 months). In the ablation zone of
      completely ablated tumors, the fat content progressively decreased (n = 4) or was
      unchanged during follow-up (n = 2). In the two tumors with local progression, the
      fat portion enlarged (n = 1) or did not change after ablation (n = 1).
      CONCLUSION: Persistence of fat in the ablation zone during imaging follow-up
      after RF ablation of fat-containing HCCs does not necessarily indicate treatment
      failure. Changes in fat content of the ablation zone during follow-up (increase
      or decrease in size) could be used as additional criteria to determine success or
      failure of RF ablation in fat-containing HCC.

PMID- 19164700
TI  - Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary
      hypertension.
AB  - RATIONALE: Transthoracic Doppler echocardiography is recommended for screening
      for the presence of pulmonary hypertension (PH). However, some recent studies
      have suggested that Doppler echocardiographic pulmonary artery pressure estimates
      may frequently be inaccurate. OBJECTIVES: Evaluate the accuracy of Doppler
      echocardiography for estimating pulmonary artery pressure and cardiac output.
      METHODS: We conducted a prospective study on patients with various forms of PH
      who underwent comprehensive Doppler echocardiography within 1 hour of a
      clinically indicated right-heart catheterization to compare noninvasive
      hemodynamic estimates with invasively measured values. MEASUREMENTS AND MAIN
      RESULTS: A total of 65 patients completed the study protocol. Using Bland-Altman
      analytic methods, the bias for the echocardiographic estimates of the pulmonary
      artery systolic pressure was -0.6 mm Hg with 95% limits of agreement ranging from
      +38.8 to -40.0 mm Hg. Doppler echocardiography was inaccurate (defined as being
      greater than +/-10 mm Hg of the invasive measurement) in 48% of cases.
      Overestimation and underestimation of pulmonary artery systolic pressure by
      Doppler echocardiography occurred with a similar frequency (16 vs. 15 instances,
      respectively). The magnitude of pressure underestimation was greater than
      overestimation (-30 +/- 16 vs. +19 +/- 11 mm Hg; P = 0.03); underestimates by
      Doppler also led more often to misclassification of the severity of the PH. For
      cardiac output measurement, the bias was -0.1 L/min with 95% limits of agreement
      ranging from +2.2 to -2.4 L/min. CONCLUSIONS: Doppler echocardiography may
      frequently be inaccurate in estimating pulmonary artery pressure and cardiac
      output in patients being evaluated for PH.

PMID- 19164701
TI  - Vitamin D beyond bones in chronic obstructive pulmonary disease: time to act.
AB  - The discovery that the vitamin D endocrine system regulates a very large number
      of genes and their associated biological processes improves our insight into the
      fundamental role of vitamin D and sun exposure for human health. Accumulating
      epidemiological data are linking a low vitamin D nutritional status to highly
      prevalent diseases such as cancer, autoimmune diseases, and chronic infections.
      Approximately half of the world's elderly, and to a lesser extent the adult
      population, have insufficient to deficient 25-hydroxyvitamin D (25-OHD) serum
      levels, and several intervention studies are being undertaken to study the impact
      of adequate vitamin D supplementation in chronic diseases. In this perspective we
      claim that chronic obstructive pulmonary disease (COPD) is a candidate disease
      for which vitamin D supplementation might be beneficial. Epidemiological studies
      revealed a dose-dependent association between serum 25-OHD levels and pulmonary
      function so that adequate vitamin D supplementation may extend beyond its
      protection against osteoporotic fractures. In line with the novel insights on its
      immune function, it is tempting to speculate that vitamin D may down-regulate the
      inflammatory immune response in the airways while boosting innate immune defense
      against different microorganisms. Apart from its affects on osteoporosis, vitamin
      D may also interfere with other comorbidities of COPD such as skeletal muscle
      weakness, cardiovascular disease, and cancer. Because respiratory treatments in
      COPD fail to reverse disease progression, interventional trials that may exploit
      the broader potential of vitamin D are warranted. A further challenge of such
      studies is to define optimal serum 25-OHD levels for such noncalcemic endpoints.

PMID- 19164702
TI  - Inhibition of PI3Kdelta restores glucocorticoid function in smoking-induced
      airway inflammation in mice.
AB  - RATIONALE: There is an increasing prevalence of reduced responsiveness to
      glucocorticoid therapy in severe asthma and chronic obstructive pulmonary disease
      (COPD). The molecular mechanism of this remains unknown. Recent studies have
      shown that histone deacetylase activity, which is critical to glucocorticoid
      function, is altered by oxidant stress and may be involved in the development of
      glucocorticoid insensitivity. OBJECTIVES: To determine the role of
      phosphoinositol-3-kinase (PI3K) in the development of cigarette smoke-induced
      glucocorticoid insensitivity. METHODS: Wild-type, PI3Kgamma knock-out and
      PI3Kdelta kinase dead knock-in transgenic mice were used in a model of cigarette
      smoke-induced glucocorticoid insensitivity. Peripheral lung tissue was obtained
      from six healthy nonsmokers, nine smokers with normal lung function, and eight
      patients with COPD. MEASUREMENTS AND MAIN RESULTS: In vitro oxidative stress
      activates PI3K and induced a relative glucocorticoid resistance, which is
      restored by PI3K inhibition. In vivo, cigarette smoke exposure in mice increased
      tyrosine nitration of histone deacetylase 2 in the lung, correlating with reduced
      histone deacetylase 2 activity and reduced glucocorticoid function. Histone
      deacetylase 2 activity and the antiinflammatory effects of glucocorticoids were
      restored in PI3Kdelta kinase dead knock-in but not PI3Kgamma knock-out smoke
      exposed mice compared with wild type mice, correlating with reduced histone
      deacetylase 2 tyrosine nitration. Glucocorticoid receptor expression was
      significantly reduced in smoke-exposed mice, in smokers with normal lung
      function, and in patients with COPD. CONCLUSIONS: These data show that
      therapeutic inhibition of PI3Kdelta may restore glucocorticoid function in
      oxidative stress-induced glucocorticoid insensitivity.

PMID- 19164704
TI  - Approach--avoidance motivation and information processing: a cross-cultural
      analysis.
AB  - Much recent research suggests that North Americans more frequently experience
      approach motivations and East Asians more frequently experience avoidance
      motivations. The current research explores some cognitive implications of this
      cultural difference. North Americans should be more attentive to approach
      oriented information, whereas East Asians should be more attentive to avoidance
      oriented information. Three studies confirmed this hypothesis. When asked to
      recall information framed in either approach or avoidance terms, a predicted
      interaction between culture and information frame was observed (Study 1 and 2).
      Moreover, analyses of consumer book reviews found that among reviews that were
      rated as helpful, approach-focused content was more prevalent in American reviews
      compared to Japanese reviews, in which avoidance-focused content was more
      prevalent (Study 3). Findings from the current research add to the growing
      literature of cross-cultural research on approach-avoidance motivations.

PMID- 19164703
TI  - Exposure to traffic and left ventricular mass and function: the Multi-Ethnic
      Study of Atherosclerosis.
AB  - RATIONALE: Ambient air pollution has been associated with heart failure morbidity
      and mortality. The mechanisms responsible for these associations are unknown but
      may include the effects of traffic-related pollutants on vascular or autonomic
      function. OBJECTIVES: We assessed the cross-sectional relation between long-term
      air pollution, traffic exposures, and important end-organ measures of alterations
      in cardiac function-left ventricular mass index (LVMI) and ejection fraction-in
      the Multi-Ethnic Study of Atherosclerosis, a multicenter study of adults without
      previous clinical cardiovascular disease. METHODS: A total of 3,827 eligible
      participants (aged 45-84 yr) underwent cardiac magnetic resonance imaging between
      2000 and 2002. We estimated air pollution exposures using residential proximity
      to major roadways and interpolated concentrations of fine particulate matter
      (less than 2.5 microns in diameter). We examined adjusted associations between
      these exposures and left ventricular mass and function. MEASUREMENTS AND MAIN
      RESULTS: Relative to participants living more than 150 m from a major roadway,
      participants living within 50 m of a major roadway showed an adjusted 1.4 g/m(2)
      (95% CI, 0.3-2.5) higher LVMI, a difference in mass corresponding to a 5.6 mm Hg
      greater systolic blood pressure. Ejection fraction was not associated with
      proximity to major roadways. Limited variability in estimates of fine particulate
      matter was observed within cities, and no associations with particulate matter
      were found for either outcome after adjustment for center. CONCLUSIONS: Living in
      close proximity to major roadways is associated with higher LVMI, suggesting
      chronic vascular end-organ damage from a traffic-related environmental exposure.
      Air pollutants or another component of roadway proximity, such as noise, could be
      responsible.

PMID- 19164705
TI  - Possible selves in marital roles: the impact of the anticipated division of labor
      on the mate preferences of women and men.
AB  - In two experiments, female and male participants envisioned themselves as a
      married person with children who is either a homemaker or a provider.
      Participants who envisioned themselves as a future homemaker regarded a potential
      mate's provider qualities as more important and homemaker qualities as less
      important, compared with participants who envisioned themselves as a future
      provider. Envisioning oneself as a homemaker also shifted preferences toward an
      older spouse, compared with envisioning oneself as a provider. In the control
      conditions of the experiments, in which participants freely envisioned their own
      future marriage, the less provider responsibility anticipated for the wife, the
      more traditional were mate preferences. These experiments support the social role
      theory view that the roles anticipated by men and women influence their choice of
      mates.

PMID- 19164708
TI  - The formation of warm dense matter: experimental evidence for electronic bond
      hardening in gold.
AB  - Under strong optical excitation conditions, it is possible to create highly
      nonequilibrium states of matter. The nuclear response is determined by the rate
      of energy transfer from the excited electrons to the nuclei and the instantaneous
      effect of change in electron distribution on the interatomic potential energy
      landscape. We used femtosecond electron diffraction to follow the structural
      evolution of strongly excited gold under these transient electronic conditions.
      Generally, materials become softer with excitation. In contrast, the rate of
      disordering of the gold lattice is found to be retarded at excitation levels up
      to 2.85 megajoules per kilogram with respect to the degree of lattice heating,
      which is indicative of increased lattice stability at high effective electronic
      temperatures, a predicted effect that illustrates the strong correlation between
      electronic structure and lattice bonding.

PMID- 19164707
TI  - Axon regeneration requires a conserved MAP kinase pathway.
AB  - Regeneration of injured neurons can restore function, but most neurons regenerate
      poorly or not at all. The failure to regenerate in some cases is due to a lack of
      activation of cell-intrinsic regeneration pathways. These pathways might be
      targeted for the development of therapies that can restore neuron function after
      injury or disease. Here, we show that the DLK-1 mitogen-activated protein (MAP)
      kinase pathway is essential for regeneration in Caenorhabditis elegans motor
      neurons. Loss of this pathway eliminates regeneration, whereas activating it
      improves regeneration. Further, these proteins also regulate the later step of
      growth cone migration. We conclude that after axon injury, activation of this MAP
      kinase cascade is required to switch the mature neuron from an aplastic state to
      a state capable of growth.

PMID- 19164706
TI  - Analysis of Drosophila segmentation network identifies a JNK pathway factor
      overexpressed in kidney cancer.
AB  - We constructed a large-scale functional network model in Drosophila melanogaster
      built around two key transcription factors involved in the process of embryonic
      segmentation. Analysis of the model allowed the identification of a new role for
      the ubiquitin E3 ligase complex factor SPOP. In Drosophila, the gene encoding
      SPOP is a target of segmentation transcription factors. Drosophila SPOP mediates
      degradation of the Jun kinase phosphatase Puckered, thereby inducing tumor
      necrosis factor (TNF)/Eiger-dependent apoptosis. In humans, we found that SPOP
      plays a conserved role in TNF-mediated JNK signaling and was highly expressed in
      99% of clear cell renal cell carcinomas (RCCs), the most prevalent form of kidney
      cancer. SPOP expression distinguished histological subtypes of RCC and
      facilitated identification of clear cell RCC as the primary tumor for metastatic
      lesions.

PMID- 19164709
TI  - Coherence factors in a high-tc cuprate probed by quasi-particle scattering off
      vortices.
AB  - When electrons pair in a superconductor, quasi-particles develop an acute
      sensitivity to different types of scattering potential that is described by the
      appearance of coherence factors in the scattering amplitudes. Although the
      effects of coherence factors are well established in isotropic superconductors,
      they are much harder to detect in their anisotropic counterparts, such as high
      superconducting-transition-temperature cuprates. We demonstrate an approach that
      highlights the momentum-dependent coherence factors in Ca2-xNaxCuO2Cl2. We used
      Fourier-transform scanning tunneling spectroscopy to reveal a magnetic-field
      dependence in quasi-particle scattering interference patterns that is sensitive
      to the sign of the anisotropic gap. This result is associated with the d-wave
      coherence factors and quasi-particle scattering off vortices. Our technique thus
      provides insights into the nature of electron pairing as well as quasi-particle
      scattering processes in unconventional superconductors.

PMID- 19164710
TI  - Redefining science education.

PMID- 19164711
TI  - Europe. Acquittals in CJD trial divide French scientists.

PMID- 19164712
TI  - Ecology. Western U.S. forests suffer death by degrees.

PMID- 19164713
TI  - Conservation biology. Debate continues over rainforest fate--with a climate
      twist.

PMID- 19164714
TI  - Wildlife biology. Confused pelicans may have lingered too long up north.

PMID- 19164715
TI  - Awards. Two Americans win Japan Prize.

PMID- 19164716
TI  - Agriculture. European pesticide rules promote resistance, researchers warn.

PMID- 19164717
TI  - Emerging infectious diseases. Scientists puzzle over Ebola-Reston virus in pigs.

PMID- 19164718
TI  - Teaching evolution. Educators decry new Louisiana policy.

PMID- 19164719
TI  - The transition. Proposed regulatory czar has long and perplexing track record.

PMID- 19164720
TI  - Biotechnology. U.S. Appellate Court weighs 'obvious' patents.

PMID- 19164721
TI  - Physics. Photon sieve lights a smooth path to entangled quantum weirdness.

PMID- 19164722
TI  - Social science. Friendship as a health factor.

PMID- 19164723
TI  - Social science. With isolation comes ill health.

PMID- 19164724
TI  - Fall meeting of the American Geophysical Union. Galloping glaciers of Greenland
      have reined themselves in.

PMID- 19164725
TI  - Fall meeting of the American Geophysical Union. Tang hints of a watery interior
      for Enceladus.

PMID- 19164726
TI  - Fall meeting of the American Geophysical Union. The many dangers of greenhouse
      acid.

PMID- 19164727
TI  - Fall meeting of the American Geophysical Union. Snapshots from the meeting.

PMID- 19164728
TI  - Bailing out creatures great and small.

PMID- 19164729
TI  - Proposed French reforms miss the mark.

PMID- 19164730
TI  - Ban impact factor manipulation.

PMID- 19164731
TI  - GOP must embrace science again.

PMID- 19164732
TI  - A word of caution on the Coca-Cola way.

PMID- 19164733
TI  - Global biological resources. Could access requirements stifle your research?

PMID- 19164734
TI  - Immunology. Ex uno plura.

PMID- 19164735
TI  - Anthropology. Where bacteria and languages concur.

PMID- 19164737
TI  - Atmosphere. Sources of Asian haze.

PMID- 19164736
TI  - Physics. Teleporting a quantum state to distant matter.

PMID- 19164738
TI  - Geochemistry. Life on an anaerobic planet.

PMID- 19164739
TI  - Cell biology. Protein filaments caught in the act.

PMID- 19164741
TI  - Earth's degassing: a missing ethane and propane source.
AB  - Current emission inventories require an additional "unknown" source to balance
      the global atmospheric budgets of ethane (C2H6). Here, we provide evidence that a
      substantial part of the missing source can be attributed to natural gas seepage
      from petroliferous, geothermal, and volcanic areas. Such geologic sources also
      inject propane (C3H8) into the atmosphere. The analysis of a large data set of
      methane (CH4), ethane, and propane concentrations in surface gas emissions of 238
      sites from different geographic and geologic areas, coupled with published
      estimates of geomethane emissions, suggests that Earth's degassing accounts for
      at least 17% and 10% of total ethane and propane emissions, respectively.

PMID- 19164740
TI  - Membrane fusion: grappling with SNARE and SM proteins.
AB  - The two universally required components of the intracellular membrane fusion
      machinery, SNARE and SM (Sec1/Munc18-like) proteins, play complementary roles in
      fusion. Vesicular and target membrane-localized SNARE proteins zipper up into an
      alpha-helical bundle that pulls the two membranes tightly together to exert the
      force required for fusion. SM proteins, shaped like clasps, bind to trans-SNARE
      complexes to direct their fusogenic action. Individual fusion reactions are
      executed by distinct combinations of SNARE and SM proteins to ensure specificity,
      and are controlled by regulators that embed the SM-SNARE fusion machinery into a
      physiological context. This regulation is spectacularly apparent in the exquisite
      speed and precision of synaptic exocytosis, where synaptotagmin (the calcium-ion
      sensor for fusion) cooperates with complexin (the clamp activator) to control the
      precisely timed release of neurotransmitters that initiates synaptic transmission
      and underlies brain function.

PMID- 19164742
TI  - Language phylogenies reveal expansion pulses and pauses in Pacific settlement.
AB  - Debates about human prehistory often center on the role that population
      expansions play in shaping biological and cultural diversity. Hypotheses on the
      origin of the Austronesian settlers of the Pacific are divided between a recent
      "pulse-pause" expansion from Taiwan and an older "slow-boat" diffusion from
      Wallacea. We used lexical data and Bayesian phylogenetic methods to construct a
      phylogeny of 400 languages. In agreement with the pulse-pause scenario, the
      language trees place the Austronesian origin in Taiwan approximately 5230 years
      ago and reveal a series of settlement pauses and expansion pulses linked to
      technological and social innovations. These results are robust to assumptions
      about the rooting and calibration of the trees and demonstrate the combined power
      of linguistic scholarship, database technologies, and computational phylogenetic
      methods for resolving questions about human prehistory.

PMID- 19164743
TI  - An entanglement filter.
AB  - The ability to filter quantum states is a key capability in quantum information
      science and technology, in which one-qubit filters, or polarizers, have found
      wide application. Filtering on the basis of entanglement requires extension to
      multi-qubit filters with qubit-qubit interactions. We demonstrated an optical
      entanglement filter that passes a pair of photons if they have the desired
      correlations of their polarization. Such devices have many important applications
      to quantum technologies.

PMID- 19164744
TI  - Quantum teleportation between distant matter qubits.
AB  - Quantum teleportation is the faithful transfer of quantum states between systems,
      relying on the prior establishment of entanglement and using only classical
      communication during the transmission. We report teleportation of quantum
      information between atomic quantum memories separated by about 1 meter. A quantum
      bit stored in a single trapped ytterbium ion (Yb+) is teleported to a second Yb+
      atom with an average fidelity of 90% over a replete set of states. The
      teleportation protocol is based on the heralded entanglement of the atoms through
      interference and detection of photons emitted from each atom and guided through
      optical fibers. This scheme may be used for scalable quantum computation and
      quantum communication.

PMID- 19164745
TI  - Complementary active sites cause size-selective reactivity of aluminum cluster
      anions with water.
AB  - The reactions of metal clusters with small molecules often depend on cluster
      size. The selectivity of oxygen reactions with aluminum cluster anions can be
      well described within an electronic shell model; however, not all reactions are
      subject to the same fundamental constraints. We observed the size selectivity of
      aluminum cluster anion reactions with water, which can be attributed to the
      dissociative chemisorption of water at specific surface sites. The reactivity
      depends on geometric rather than electronic shell structure. Identical
      arrangements of multiple active sites in Al16-, Al17-, and Al18- result in the
      production of H2 from water.

PMID- 19164746
TI  - Brown clouds over South Asia: biomass or fossil fuel combustion?
AB  - Carbonaceous aerosols cause strong atmospheric heating and large surface cooling
      that is as important to South Asian climate forcing as greenhouse gases, yet the
      aerosol sources are poorly understood. Emission inventory models suggest that
      biofuel burning accounts for 50 to 90% of emissions, whereas the elemental
      composition of ambient aerosols points to fossil fuel combustion. We used
      radiocarbon measurements of winter monsoon aerosols from western India and the
      Indian Ocean to determine that biomass combustion produced two-thirds of the bulk
      carbonaceous aerosols, as well as one-half and two-thirds of two black carbon
      subfractions, respectively. These constraints show that both biomass combustion
      (such as residential cooking and agricultural burning) and fossil fuel combustion
      should be targeted to mitigate climate effects and improve air quality.

PMID- 19164747
TI  - Genetic interactions between transcription factors cause natural variation in
      yeast.
AB  - Our understanding of the genetic basis of phenotypic diversity is limited by the
      paucity of examples in which multiple, interacting loci have been identified. We
      show that natural variation in the efficiency of sporulation, the program in
      yeast that initiates the sexual phase of the life cycle, between oak tree and
      vineyard strains is due to allelic variation between four nucleotide changes in
      three transcription factors: IME1, RME1, and RSF1. Furthermore, we identified
      that selection has shaped quantitative variation in yeast sporulation between
      strains. These results illustrate how genetic interactions between transcription
      factors are a major source of phenotypic diversity within species.

PMID- 19164748
TI  - Different T cell receptor signals determine CD8+ memory versus effector
      development.
AB  - Following infection, naive CD8+ T cells bearing pathogen-specific T cell
      receptors (TCRs) differentiate into a mixed population of short-lived effector
      and long-lived memory T cells to mediate an adaptive immune response. How the TCR
      regulates memory T cell development has remained elusive. Using a mutant TCR
      transgenic model, we found that point mutations in the TCR beta transmembrane
      domain (betaTMD) impair the development and function of CD8+ memory T cells
      without affecting primary effector T cell responses. Mutant T cells are deficient
      in polarizing the TCR and in organizing the nuclear factor kappaB signal at the
      immunological synapse. Thus, effector and memory states of CD8+ T cells are
      separable fates, determined by differential TCR signaling.

PMID- 19164749
TI  - Secondary replicative function of CD8+ T cells that had developed an effector
      phenotype.
AB  - Models of the differentiation of memory CD8+ T cells that replicate during
      secondary infections differ over whether such cells had acquired effector
      function during primary infections. We created a transgenic mouse line that
      permits mapping of the fate of granzyme B (gzmB)-expressing CD8+ T cells and
      their progeny by indelibly marking them with enhanced yellow fluorescent protein
      (EYFP). Virus-specific CD8+ T cells express gzmB within the first 2 days of a
      primary response to infection with influenza, without impairment of continued
      primary clonal expansion. On secondary infection, virus-specific CD8+ T cells
      that became EYFP+ during a primary infection clonally expand as well as all virus
      specific CD8+ T cells. Thus, CD8+ T cells that have acquired an effector
      phenotype during primary infection may function as memory cells with replicative
      function.

PMID- 19164750
TI  - Alternative zippering as an on-off switch for SNARE-mediated fusion.
AB  - Membrane fusion between vesicles and target membranes involves the zippering of a
      four-helix bundle generated by constituent helices derived from target- and
      vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptors
      (SNAREs). In neurons, the protein complexin clamps otherwise spontaneous fusion
      by SNARE proteins, allowing neurotransmitters and other mediators to be secreted
      when and where they are needed as this clamp is released. The membrane-proximal
      accessory helix of complexin is necessary for clamping, but its mechanism of
      action is unknown. Here, we present experiments using a reconstituted fusion
      system that suggest a simple model in which the complexin accessory helix forms
      an alternative four-helix bundle with the target-SNARE near the membrane,
      preventing the vesicle-SNARE from completing its zippering.

PMID- 19164751
TI  - Complexin controls the force transfer from SNARE complexes to membranes in
      fusion.
AB  - Trans-SNAP receptor (SNARE, where SNAP is defined as soluble NSF attachment
      protein, and NSF is defined as N-ethylmaleimide-sensitive factor) complexes
      catalyze synaptic vesicle fusion and bind complexin, but the function of
      complexin binding to SNARE complexes remains unclear. Here we show that in
      neuronal synapses, complexin simultaneously suppressed spontaneous fusion and
      activated fast calcium ion-evoked fusion. The dual function of complexin required
      SNARE binding and also involved distinct amino-terminal sequences of complexin
      that localize to the point where trans-SNARE complexes insert into the fusing
      membranes, suggesting that complexin controls the force that trans-SNARE
      complexes apply onto the fusing membranes. Consistent with this hypothesis, a
      mutation in the membrane insertion sequence of the v-SNARE synaptobrevin/vesicle
      associated membrane protein (VAMP) phenocopied the complexin loss-of-function
      state without impairing complexin binding to SNARE complexes. Thus, complexin
      probably activates and clamps the force transfer from assembled trans-SNARE
      complexes onto fusing membranes.

PMID- 19164752
TI  - Widespread increase of tree mortality rates in the western United States.
AB  - Persistent changes in tree mortality rates can alter forest structure,
      composition, and ecosystem services such as carbon sequestration. Our analyses of
      longitudinal data from unmanaged old forests in the western United States showed
      that background (noncatastrophic) mortality rates have increased rapidly in
      recent decades, with doubling periods ranging from 17 to 29 years among regions.
      Increases were also pervasive across elevations, tree sizes, dominant genera, and
      past fire histories. Forest density and basal area declined slightly, which
      suggests that increasing mortality was not caused by endogenous increases in
      competition. Because mortality increased in small trees, the overall increase in
      mortality rates cannot be attributed solely to aging of large trees. Regional
      warming and consequent increases in water deficits are likely contributors to the
      increases in tree mortality rates.

PMID- 19164753
TI  - The peopling of the Pacific from a bacterial perspective.
AB  - Two prehistoric migrations peopled the Pacific. One reached New Guinea and
      Australia, and a second, more recent, migration extended through Melanesia and
      from there to the Polynesian islands. These migrations were accompanied by two
      distinct populations of the specific human pathogen Helicobacter pylori, called
      hpSahul and hspMaori, respectively. hpSahul split from Asian populations of H.
      pylori 31,000 to 37,000 years ago, in concordance with archaeological history.
      The hpSahul populations in New Guinea and Australia have diverged sufficiently to
      indicate that they have remained isolated for the past 23,000 to 32,000 years.
      The second human expansion from Taiwan 5000 years ago dispersed one of several
      subgroups of the Austronesian language family along with one of several hspMaori
      clades into Melanesia and Polynesia, where both language and parasite have
      continued to diverge.

PMID- 19164755
TI  - Identification of small-molecule inducers of pancreatic beta-cell expansion.
AB  - To identify small molecules that can induce beta-cell replication, a large
      chemical library was screened for proliferation of growth-arrested, reversibly
      immortalized mouse beta cells by using an automated high-throughput screening
      platform. A number of structurally diverse, active compounds were identified,
      including phorbol esters, which likely act through protein kinase C, and a group
      of thiophene-pyrimidines that stimulate beta-cell proliferation by activating the
      Wnt signaling pathway. A group of dihydropyridine (DHP) derivatives was also
      shown to reversibly induce beta-cell replication in vitro by activating L-type
      calcium channels (LTCCs). Our data suggest that the LTCC agonist 2a affects the
      expression of genes involved in cell cycle progression and cellular
      proliferation. Furthermore, treatment of beta cells with both LTCC agonist 2a and
      the Glp-1 receptor agonist Exendin-4 showed an additive effect on beta-cell
      replication. The identification of small molecules that induce beta-cell
      proliferation suggests that it may be possible to reversibly expand other
      quiescent cells to overcome deficits associated with degenerative and/or
      autoimmune diseases.

PMID- 19164756
TI  - Source modeling sleep slow waves.
AB  - Slow waves are the most prominent electroencephalographic (EEG) feature of sleep.
      These waves arise from the synchronization of slow oscillations in the membrane
      potentials of millions of neurons. Scalp-level studies have indicated that slow
      waves are not instantaneous events, but rather they travel across the brain.
      Previous studies of EEG slow waves were limited by the poor spatial resolution of
      EEGs and by the difficulty of relating scalp potentials to the activity of the
      underlying cortex. Here we use high-density EEG (hd-EEG) source modeling to show
      that individual spontaneous slow waves have distinct cortical origins, propagate
      uniquely across the cortex, and involve unique subsets of cortical structures.
      However, when the waves are examined en masse, we find that there are diffuse hot
      spots of slow wave origins centered on the lateral sulci. Furthermore, slow wave
      propagation along the anterior-posterior axis of the brain is largely mediated by
      a cingulate highway. As a group, slow waves are associated with large currents in
      the medial frontal gyrus, the middle frontal gyrus, the inferior frontal gyrus,
      the anterior cingulate, the precuneus, and the posterior cingulate. These areas
      overlap with the major connectional backbone of the cortex and with many parts of
      the default network.

PMID- 19164757
TI  - ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3
      only protein NOXA in cancer cells.
AB  - The ubiquitin-proteasome system has recently emerged as a major target for drug
      development in cancer therapy. The proteasome inhibitor bortezomib has clinical
      activity in multiple myeloma and mantle cell lymphoma. Here we report that
      Eeyarestatin I (EerI), a chemical inhibitor that blocks endoplasmic reticulum
      (ER)-associated protein degradation, has antitumor and biologic activities
      similar to bortezomib and can synergize with bortezomib. Like bortezomib, EerI
      induced cytotoxicity requires the up-regulation of the Bcl-2 homology3 (BH3)-only
      pro-apoptotic protein NOXA. We further demonstrate that both EerI and bortezomib
      activate NOXA via an unanticipated mechanism that requires cooperation between
      two processes. First, these agents elicit an integrated stress response program
      at the ER to activate the CREB/ATF transcription factors ATF3 and ATF4. We show
      that ATF3 and ATF4 form a complex capable of binding to the NOXA promoter, which
      is required for NOXA activation. Second, EerI and bortezomib also block
      ubiquitination of histone H2A to relieve its inhibition on NOXA transcription.
      Our results identify a class of anticancer agents that integrate ER stress
      response with an epigenetic mechanism to induce cell death.

PMID- 19164758
TI  - Quantifying environmental adaptation of metabolic pathways in metagenomics.
AB  - Recently, approaches have been developed to sample the genetic content of
      heterogeneous environments (metagenomics). However, by what means these sequences
      link distinct environmental conditions with specific biological processes is not
      well understood. Thus, a major challenge is how the usage of particular pathways
      and subnetworks reflects the adaptation of microbial communities across
      environments and habitats-i.e., how network dynamics relates to environmental
      features. Previous research has treated environments as discrete, somewhat
      simplified classes (e.g., terrestrial vs. marine), and searched for obvious
      metabolic differences among them (i.e., treating the analysis as a typical
      classification problem). However, environmental differences result from
      combinations of many factors, which often vary only slightly. Therefore, we
      introduce an approach that employs correlation and regression to relate multiple,
      continuously varying factors defining an environment to the extent of particular
      microbial pathways present in a geographic site. Moreover, rather than looking
      only at individual correlations (one-to-one), we adapted canonical correlation
      analysis and related techniques to define an ensemble of weighted pathways that
      maximally covaries with a combination of environmental variables (many-to-many),
      which we term a metabolic footprint. Applied to available aquatic datasets, we
      identified footprints predictive of their environment that can potentially be
      used as biosensors. For example, we show a strong multivariate correlation
      between the energy-conversion strategies of a community and multiple
      environmental gradients (e.g., temperature). Moreover, we identified covariation
      in amino acid transport and cofactor synthesis, suggesting that limiting amounts
      of cofactor can (partially) explain increased import of amino acids in nutrient
      limited conditions.

PMID- 19164759
TI  - Emergence of species in evolutionary "simulated annealing".
AB  - Which factors govern the evolution of mutation rates and emergence of species?
      Here, we address this question by using a first principles model of life where
      population dynamics of asexual organisms is coupled to molecular properties and
      interactions of proteins encoded in their genomes. Simulating evolution of
      populations, we found that fitness increases in punctuated steps via epistatic
      events, leading to formation of stable and functionally interacting proteins. At
      low mutation rates, species form populations of organisms tightly localized in
      sequence space, whereas at higher mutation rates, species are lost without an
      apparent loss of fitness. However, when mutation rate was a selectable trait, the
      population initially maintained high mutation rate until a high fitness level was
      reached, after which organisms with low mutation rates are gradually selected,
      with the population eventually reaching mutation rates comparable with those of
      modern DNA-based organisms. This study shows that the fitness landscape of a
      biophysically realistic system is extremely complex, with huge number of local
      peaks rendering adaptation dynamics to be a glass-like process. On a more
      practical level, our results provide a rationale to experimental observations of
      the effect of mutation rate on fitness of populations of asexual organisms.

PMID- 19164760
TI  - The nature of the TRAP-Anti-TRAP complex.
AB  - Tryptophan biosynthesis is subject to exquisite control in species of Bacillus
      and has become one of the best-studied model systems in gene regulation. The
      protein TRAP (trp RNA-binding attenuation protein) predominantly forms a ring
      shaped 11-mer, which binds cognate RNA in the presence of tryptophan to suppress
      expression of the trp operon. TRAP is itself regulated by the protein Anti-TRAP,
      which binds to TRAP and prevents RNA binding. To date, the nature of this
      interaction has proved elusive. Here, we describe mass spectrometry and
      analytical centrifugation studies of the complex, and 2 crystal structures of the
      TRAP-Anti-TRAP complex. These crystal structures, both refined to 3.2-A
      resolution, show that Anti-TRAP binds to TRAP as a trimer, sterically blocking
      RNA binding. Mass spectrometry shows that 11-mer TRAP may bind up to 5 AT
      trimers, and an artificial 12-mer TRAP may bind 6. Both forms of TRAP make the
      same interactions with Anti-TRAP. Crystallization of wild-type TRAP with Anti
      TRAP selectively pulls the 12-mer TRAP form out of solution, so the crystal
      structure of wild-type TRAP-Anti-TRAP complex reflects a minor species from a
      mixed population.

PMID- 19164761
TI  - Apolipoprotein E epsilon4 is associated with disease-specific effects on brain
      atrophy in Alzheimer's disease and frontotemporal dementia.
AB  - Apolipoprotein epsilon4 (apoE4) has been strongly linked with Alzheimer's disease
      (AD) and contributes to several other neurological disorders. We investigated the
      influence of epsilon4 allele carrier status on the pattern of gray matter atrophy
      and disease severity in 51 patients with probable AD and 31 patients with
      behavioral variant frontotemporal dementia (bvFTD), compared with 56 healthy
      controls. Voxel-based morphometry was performed by using statistical parametric
      mapping. The epsilon4 allele frequency was higher in the AD group (P < 0.001)
      than the controls but not in the bvFTD group. No differences in demographic or
      cognitive profiles were observed between epsilon4 allele carriers and noncarriers
      within any of the diagnostic groups. However, epsilon4 carrier status was
      associated with more severe brain atrophy in disease-specific regions compared
      with noncarriers in both AD and bvFTD. AD epsilon4 carriers showed greater
      atrophy in the bilateral parietal cortex and right hippocampus, and bvFTD
      epsilon4 carriers demonstrated greater atrophy in the bilateral medial,
      dorsolateral, and orbital frontal cortex, anterior insula, and cingulate cortex
      with right predominance. This regional epsilon4 effect is consistent with the
      hypothesis that apoE may affect the morphologic expression uniquely in different
      neurodegenerative diseases. The atrophy patterns in epsilon4 carriers may
      indicate that they are at greater risk for clinical progression.

PMID- 19164762
TI  - Na,K-ATPase signal transduction triggers CREB activation and dendritic growth.
AB  - Dendritic growth is pivotal in the neurogenesis of cortical neurons. The sodium
      pump, or Na,K-ATPase, is an evolutionarily conserved protein that, in addition to
      its central role in establishing the electrochemical gradient, has recently been
      reported to function as a receptor and signaling mediator. Although a large body
      of evidence points toward a dual function for the Na,K-ATPase, few biological
      implications of this signaling pathway have been described. Here we report that
      Na,K-ATPase signal transduction triggers dendritic growth as well as a
      transcriptional program dependent on cAMP response element binding protein (CREB)
      and cAMP response element (CRE)-mediated gene expression, primarily regulated via
      Ca(2+)/calmodulin-dependent protein (CaM) kinases. The signaling cascade
      mediating dendritic arbor growth also involves intracellular Ca(2+) oscillations
      and sustained phosphorylation of mitogen-activated protein (MAP) kinases. Thus,
      our results suggest a novel role for the Na,K-ATPase as a modulator of dendritic
      growth in developing neurons.

PMID- 19164763
TI  - Cellulosic ethanol production from AFEX-treated corn stover using Saccharomyces
      cerevisiae 424A(LNH-ST).
AB  - Current technology using corn stover (CS) as feedstock, Ammonia Fiber Expansion
      (AFEX) as the pretreatment technology, and Saccharomyces cerevisiae 424A(LNH-ST)
      as the ethanologenic strain in Separate Hydrolysis and Fermentation was able to
      achieve 191.5 g EtOH/kg untreated CS, at an ethanol concentration of 40.0 g/L
      (5.1 vol/vol%) without washing of pretreated biomass, detoxification, or nutrient
      supplementation. Enzymatic hydrolysis at high solids loading was identified as
      the primary bottleneck affecting overall ethanol yield and titer. Degradation
      compounds in AFEX-pretreated biomass were shown to increase metabolic yield and
      specific ethanol production while decreasing the cell biomass generation.
      Nutrients inherently present in CS and those resulting from biomass processing
      are sufficient to support microbial growth during fermentation. This platform
      offers the potential to improve the economics of cellulosic ethanol production by
      reducing the costs associated with raw materials, process water, and capital
      equipment.

PMID- 19164764
TI  - Gfi-1 represses CDKN2B encoding p15INK4B through interaction with Miz-1.
AB  - Gfi-1 is a nuclear zinc finger (ZF) transcriptional repressor that plays an
      important role in hematopoiesis and inner ear development, and has been
      implicated in lymphomagenesis. Gfi-1 represses transcription by directly binding
      to the consensus DNA sequence in the promoters of its target genes. We report
      here an alternative mechanism by which Gfi-1 represses CDKN2B encoding
      p15(INK4B). Gfi-1 does not directly bind to CDKN2B, but interacts with Miz-1 and,
      via Miz-1, is recruited to the core promoter of CDKN2B. Miz-1 is a POZ-ZF
      transcription factor that has been shown to mediate transcriptional repression by
      c-Myc. Like c-Myc, upon recruitment to the CDKN2B promoter, Gfi-1 represses
      transcriptional activation of CDKN2B by Miz-1 and in response to TGFbeta.
      Consistent with its role in repressing CDKN2B transcription, knockdown of Gfi-1
      in human leukemic cells or deficiency of Gfi-1 in mouse bone marrow cells results
      in augmented expression of p15(INK4B). Notably, Gfi-1 and c-Myc are both
      recruited to the CDKN2B core promoter and act in collaboration to repress CDKN2B.
      Our data reveal a mechanism of transcriptional repression by Gfi-1 and may have
      important implications for understanding the roles of Gfi-1 in normal development
      and tumorigenesis.

PMID- 19164765
TI  - The Paf1 complex is required for efficient transcription elongation by RNA
      polymerase I.
AB  - Regulation of RNA polymerase I (Pol I) transcription is critical for controlling
      ribosome synthesis. Most previous investigations into Pol I transcription
      regulation have focused on transcription initiation. To date, the factors
      involved in the control of Pol I transcription elongation are poorly understood.
      The Paf1 complex (Paf1C) is a well-defined factor that influences polymerase II
      (Pol II) transcription elongation. We found that Paf1C associates with rDNA.
      Deletion of genes for Paf1C subunits (CDC73, CTR9, or PAF1) reduces the rRNA
      synthesis rate; however, there is no significant alteration of rDNA copy number
      or Pol I occupancy of the rDNA. Furthermore, EM analysis revealed a substantial
      increase in the frequency of large gaps between transcribing polymerases in
      ctr9Delta mutant cells compared with WT. Together, these data indicate that Paf1C
      promotes Pol I transcription through the rDNA by increasing the net rate of
      elongation. Thus, the multifunctional, conserved transcription factor Paf1C plays
      an important role in transcription elongation by Pol I in vivo.

PMID- 19164766
TI  - Evidence that DmMANF is an invertebrate neurotrophic factor supporting
      dopaminergic neurons.
AB  - In vertebrates the development and function of the nervous system is regulated by
      neurotrophic factors (NTFs). Despite extensive searches no neurotrophic factors
      have been found in invertebrates. However, cell ablation studies in Drosophila
      suggest trophic interaction between neurons and glia. Here we report the
      invertebrate neurotrophic factor in Drosophila, DmMANF, homologous to mammalian
      MANF and CDNF. DmMANF is expressed in glia and essential for maintenance of
      dopamine positive neurites and dopamine levels. The abolishment of both maternal
      and zygotic DmMANF leads to the degeneration of axonal bundles in the embryonic
      central nervous system and subsequent nonapoptotic cell death. The rescue
      experiments confirm DmMANF as a functional ortholog of the human MANF gene thus
      opening the window for comparative studies of this protein family with potential
      for the treatment of Parkinson's disease.

PMID- 19164767
TI  - Comparative sequence analysis of MONOCULM1-orthologous regions in 14 Oryza
      genomes.
AB  - Comparative genomics is a powerful tool to decipher gene and genome evolution.
      Placing multiple genome comparisons in a phylogenetic context improves the
      sensitivity of evolutionary inferences. In the genus Oryza, this comparative
      approach can be used to investigate gene function, genome evolution,
      domestication, polyploidy, and ecological adaptation. A large genomic region
      surrounding the MONOCULM1 (MOC1) locus was chosen for study in 14 Oryza species,
      including 10 diploids and 4 allotetraploids. Sequencing and annotation of 18
      bacterial artificial chromosome clones for these species revealed highly
      conserved gene colinearity and structure in the MOC1 region. Since the Oryza
      radiation about 14 Mya, differences in transposon amplification appear to be
      responsible for the different current sizes of the Oryza genomes. In the MOC1
      region, transposons were only conserved between genomes of the same type (e.g.,
      AA or BB). In addition to the conserved gene content, several apparent genes have
      been generated de novo or uniquely retained in the AA lineage. Two different 3
      gene segments have been inserted into the MOC1 region of O. coarctata (KK) or O.
      sativa by unknown mechanism(s). Large and apparently noncoding sequences flanking
      the MOC1 gene were observed to be under strong purifying selection. The
      allotetraploids Oryza alta and Oryza minuta were found to be products of recent
      polyploidization, less than 1.6 and 0.4 Mya, respectively. In allotetraploids,
      pseudogenization of duplicated genes was common, caused by large deletions, small
      frame-shifting insertions/deletions, or nonsense mutations.

PMID- 19164768
TI  - A class of selective antibacterials derived from a protein kinase inhibitor
      pharmacophore.
AB  - As the need for novel antibiotic classes to combat bacterial drug resistance
      increases, the paucity of leads resulting from target-based antibacterial
      screening of pharmaceutical compound libraries is of major concern. One
      explanation for this lack of success is that antibacterial screening efforts have
      not leveraged the eukaryotic bias resulting from more extensive chemistry efforts
      targeting eukaryotic gene families such as G protein-coupled receptors and
      protein kinases. Consistent with a focus on antibacterial target space resembling
      these eukaryotic targets, we used whole-cell screening to identify a series of
      antibacterial pyridopyrimidines derived from a protein kinase inhibitor
      pharmacophore. In bacteria, the pyridopyrimidines target the ATP-binding site of
      biotin carboxylase (BC), which catalyzes the first enzymatic step of fatty acid
      biosynthesis. These inhibitors are effective in vitro and in vivo against
      fastidious gram-negative pathogens including Haemophilus influenzae. Although the
      BC active site has architectural similarity to those of eukaryotic protein
      kinases, inhibitor binding to the BC ATP-binding site is distinct from the
      protein kinase-binding mode, such that the inhibitors are selective for bacterial
      BC. In summary, we have discovered a promising class of potent antibacterials
      with a previously undescribed mechanism of action. In consideration of the
      eukaryotic bias of pharmaceutical libraries, our findings also suggest that
      pursuit of a novel inhibitor leads for antibacterial targets with active-site
      structural similarity to known human targets will likely be more fruitful than
      the traditional focus on unique bacterial target space, particularly when
      structure-based and computational methodologies are applied to ensure bacterial
      selectivity.

PMID- 19164769
TI  - A calpain unique to alveolates is essential in Plasmodium falciparum and its
      knockdown reveals an involvement in pre-S-phase development.
AB  - Plasmodium falciparum encodes a single calpain that has a distinct domain
      composition restricted to alveolates. To evaluate the potential of this protein
      as a drug target, we assessed its essentiality. Both gene disruption by double
      cross-over and gene truncation by single cross-over recombination failed. We were
      also unable to achieve allelic replacement by using a missense mutation at the
      catalytic cysteine codon, although we could obtain synonymous allelic replacement
      parasites. These results suggested that the calpain gene and its proteolytic
      activity are important for optimal parasite growth. To gain further insight into
      its biological role, we used the FKBP degradation domain system to generate a
      fusion protein whose stability in transfected parasites could be modulated by a
      small FKBP ligand, Shield1 (Shld1). We made a calpain-GFP-FKBP fusion through
      single cross-over integration at the endogenous calpain locus. Calpain levels
      were knocked down and parasite growth was greatly impaired in the absence of
      Shld1. Parasites were delayed in their ability to transition out of the ring
      stage and in their ability to progress to the S phase. Calpain is required for
      cell cycle progression in Plasmodium parasites and appears to be an attractive
      drug target. We have shown that regulated knockdowns are possible in P.
      falciparum and can be useful for evaluating essentiality and function.

PMID- 19164770
TI  - Human muscle protein synthesis and breakdown during and after exercise.
AB  - Skeletal muscle demonstrates extraordinary mutability in its responses to
      exercise of different modes, intensity, and duration, which must involve
      alterations of muscle protein turnover, both acutely and chronically. Here, we
      bring together information on the alterations in the rates of synthesis and
      degradation of human muscle protein by different types of exercise and the
      influences of nutrition, age, and sexual dimorphism. Where possible, we summarize
      the likely changes in activity of signaling proteins associated with control of
      protein turnover. Exercise of both the resistance and nonresistance types appears
      to depress muscle protein synthesis (MPS), whereas muscle protein breakdown (MPB)
      probably remains unchanged during exercise. However, both MPS and MPB are
      elevated after exercise in the fasted state, when net muscle protein balance
      remains negative. Positive net balance is achieved only when amino acid
      availability is increased, thereby raising MPS markedly. However, postexercise
      increased amino acid availability is less important for inhibiting MPB than
      insulin, the secretion of which is stimulated most by glucose availability,
      without itself stimulating MPS. Exercise training appears to increase basal
      muscle protein turnover, with differential responses of the myofibrillar and
      mitochondrial protein fractions to acute exercise in the trained state. Aging
      reduces the responses of myofibrillar protein and anabolic signaling to
      resistance exercise. There appear to be few, if any, differences in the response
      of young women and young men to acute exercise, although there are indications
      that, in older women, the responses may be blunted more than in older men.

PMID- 19164771
TI  - Combination of hormone replacement therapy and high physical activity is
      associated with differences in Achilles tendon size in monozygotic female twin
      pairs.
AB  - Estrogen concentration has been suggested to play a role in tendon abnormalities
      and injury. In physically active postmenopausal women, hormone replacement
      therapy (HRT) has been suggested to decrease tendon diameter. We hypothesized
      that HRT use and physical activity are associated with Achilles tendon size and
      tissue structure. The study applied cotwin analysis of fourteen 54- to 62-yr-old
      identical female twin pairs with current discordance for HRT use for an average
      of 7 yr. Achilles tendon thickness and cross-sectional areas were determined by
      ultrasonography, and tendon structural organization was analyzed from the images
      using linear discriminant analysis (LDA). Maximal voluntary and twitch torques
      from plantar flexor muscles were measured. Serum levels of estradiol, estrone,
      testosterone, and sex hormone binding globulin were analyzed. Total daily
      metabolic equivalent score (MET-h/day) was calculated from physical activity
      questionnaires. Results showed that, in five physically active (MET > 4) pairs,
      the cotwins receiving HRT had greater estradiol level (P = 0.043) and smaller
      tendon cross-sectional area than their sisters (63 vs. 71 mm(2), P = 0.043).
      Among all pairs, Achilles tendon thickness and cross-sectional area did not
      significantly differ between HRT using and nonusing twin sisters. Intrapair
      correlation for Achilles tendon thickness was high, despite HRT use discordance
      (r = 0.84, P < 0.001). LDA distinguished different tendon structure only from two
      of six examined twin pairs who had a similar level of physical activity. In
      conclusion, the effect of HRT on Achilles tendon characteristics independent of
      genetic confounding may be present only in the presence of sufficient physical
      activity. In physically active twin pairs, the higher level of estrogen seems to
      be associated with smaller tendon size.

PMID- 19164772
TI  - Consecutive bouts of diverse contractile activity alter acute responses in human
      skeletal muscle.
AB  - We examined acute molecular responses in skeletal muscle to divergent exercise
      stimuli by combining consecutive bouts of resistance and endurance exercise.
      Eight men [22.9 +/- 6.3 yr, body mass of 73.2 +/- 4.5 kg, peak O(2) uptake
      (Vo(2peak)) of 54.0 +/- 5.7 ml.kg(-1) x min(-1)] were randomly assigned to
      complete trials consisting of either resistance exercise (8 x 5 leg extension,
      80% 1 repetition maximum) followed by a bout of endurance exercise (30 min
      cycling, 70% Vo(2peak)) or vice versa. Muscle biopsies were obtained from the
      vastus lateralis at rest, 15 min after each exercise bout, and after 3 h of
      passive recovery to determine early signaling and mRNA responses. Phosphorylation
      of Akt and Akt1(Ser473) were elevated 15 min after resistance exercise compared
      with cycling, with the greatest increase observed when resistance exercise
      followed cycling ( approximately 55%; P < 0.01). TSC2-mTOR-S6 kinase
      phosphorylation 15 min after each bout of exercise was similar regardless of the
      exercise mode. The cumulative effect of combined exercise resulted in disparate
      mRNA responses. IGF-I mRNA content was reduced when cycling preceded resistance
      exercise (-42%), whereas muscle ring finger mRNA was elevated when cycling was
      undertaken after resistance exercise ( approximately 52%; P < 0.05). The
      hexokinase II mRNA level was higher after resistance cycling ( approximately 45%;
      P < 0.05) than after cycling-resistance exercise, whereas modest increases in
      peroxisome proliferator-activated receptor gamma coactivator-1alpha mRNA did not
      reveal an order effect. We conclude that acute responses to diverse bouts of
      contractile activity are modified by the exercise order. Moreover, undertaking
      divergent exercise in close proximity influences the acute molecular profile and
      likely exacerbates acute "interference."

PMID- 19164773
TI  - Laryngeal constriction during hypoxic gasping and its role in improving
      autoresuscitation in two mouse strains.
AB  - Laryngeal closure following hypoxic gasps has been documented, but its efficacy
      in improving autoresuscitation capacity is unknown. We studied SWR/J mice who
      normally cannot autoresuscitate and the C57/BLJ strain who can. We evaluated the
      effects of elevated end-inspiratory lung volume immediately following a gasp. We
      compared upper airway-intact mice with tracheostomized mice in which the vocal
      cords are bypassed. We used the techniques of repeated autoresuscitate trials to
      test autoresuscitation capability. Both SWR/J and C57/BLJ mice could maintain
      elevated lung volume immediately after a gasp (breath holding). Such breath
      holding increased autoresuscitation ability in C57/BLJ mice but did not in SWR/J
      mice. In SWR/J mice, the duration of the breath holds was less than that in the
      C57/BLJ mice. These findings indicate that gasp-associated breath holding
      improves autoresuscitation capability during repeated autoresuscitation trials.
      Also, they show that SWR/J mice have a deficiency in central nervous system
      mechanisms regulating glottic closure during hypoxic gasping.

PMID- 19164774
TI  - A sex-specific relationship between capillary density and anaerobic threshold.
AB  - Although both capillary density and peak oxygen consumption (Vo(2)) improve with
      exercise training, it is difficult to find a relationship between these two
      measures. It has been suggested that peak Vo(2) may be more related to central
      hemodynamics than to the oxidative potential of skeletal muscle, which may
      account for this observation. We hypothesized that change in a measure of
      submaximal performance, anaerobic threshold, might be related to change in
      skeletal muscle capillary density, a marker of oxidative potential in muscle,
      with training. Due to baseline differences among these variables, we also
      hypothesized that relationships might be sex specific. A group of 21 subjects
      completed an inactive control period, whereas 28 subjects (17 men and 11 women)
      participated in a 6-mo high-intensity exercise program. All subjects were
      sedentary, overweight, and dyslipidemic. Potential relationships were assessed
      between change in capillary density with both change in Vo(2) at peak and at
      anaerobic threshold with exercise training. All variables and relationships were
      assessed for sex-specific effects. Change in peak Vo(2) was not related to change
      in capillary density after exercise training in either sex. Men had a positive
      correlation between change in Vo(2) at anaerobic threshold and change in
      capillary density with exercise training (r = 0.635; P < 0.01), whereas women had
      an inverse relationship (r = -0.636; P < 0.05) between the change in these
      variables. These findings suggest that, although enhanced capillary density is
      associated with training-induced improvements in submaximal performance in men,
      this relationship is different in women.

PMID- 19164775
TI  - Complexity of force output during static exercise in individuals with Down
      syndrome.
AB  - Force variability is greater in individuals with Down syndrome (DS) compared with
      persons without DS and is similar to that seen with normal aging. The purpose of
      this study was to examine the structure (in both time and frequency domains) of
      force output variability in persons with DS to determine whether deficits in
      force control are similar between individuals with DS and older adults. An
      isometric handgrip task at a constant force (30% of maximal voluntary
      contraction) was completed by individuals with DS (n = 29, age 26 yr), and
      healthy young (n = 26, age 27 yr) and older (n = 33, age 70 yr) individuals.
      Mean, standard deviation (SD), and coefficient of variation (CV) were used to
      analyze the magnitude of force output variability. Spectral analysis and
      approximate entropy (ApEn) were used to analyze the structure of force output
      variability. Mean force output for DS was lower than in young controls (P < 0.05)
      but no different from old controls. Individuals with DS had greater SD and CV
      than young and old controls (P < 0.05). The DS group had a significantly greater
      proportion of spectral power within the 0-to 4-Hz bandwidth than the young and
      older controls (P < 0.05). The DS group had significantly lower ApEn values than
      the young controls (P < 0.05), but there were no differences in ApEn between the
      DS group and the old controls (P > 0.05). In conclusion, young persons with DS
      demonstrate enhanced temporal structure and greater amplitude of low-frequency
      oscillations in the force output signal than age-matched non-DS peers.
      Interestingly, young persons with DS and older persons without DS have similar
      time-dependent structure of force output variability. This would suggest a
      possible link between premature aging and less complex force output in persons
      with DS.

PMID- 19164776
TI  - Distinct muscle fascicle length changes in feline medial gastrocnemius and soleus
      muscles during slope walking.
AB  - On the basis of differences in physiology, e.g., histochemical properties and
      spindle density, and the structural design of the cat soleus (SO) and medial
      gastrocnemius (MG) muscles, we hypothesized that 1) fascicle length changes
      during overground walking would be both muscle and slope dependent, which would
      have implications for the muscles' force output as well as sensory function, and
      that 2) muscle-tendon unit (MTU) and fascicle length changes would be different,
      in which case MTU length could not be used as an indicator of muscle spindle
      strain. To test these hypotheses, we quantified muscle fascicle length changes
      and compared them with length changes of the whole MTU in the SO and MG during
      overground walking at various slopes (0, +/- 25, +/- 50, +75, and +100%). The SO
      and MG were surgically instrumented with sonomicrometry crystals and fine-wire
      electromyogram electrodes to measure changes in muscle fascicle length and muscle
      activity, respectively. MTU lengths were calculated using recorded ankle and knee
      joint angles and a geometric model of the hindlimb. The resultant joint moments
      were calculated using inverse dynamics analysis to infer muscle loading. It was
      found that although MTU length and velocity profiles of the SO and MG appeared
      similar, length changes and velocities of muscle fascicles were substantially
      different between the two muscles. Fascicle length changes of both SO and MG were
      significantly affected by slope intensity acting eccentrically in downslope
      walking (-25 to -50%) and concentrically in upslope walking (+25 to +100%). The
      differences in MTU and fascicle behaviors in both the SO and MG muscles during
      slope walking were explained by the three distinct features of these muscles: 1)
      the number of joints spanned, 2) the pennation angle, and 3) the in-series
      elastic component. It was further suggested that the potential role of length
      feedback from muscle spindles is both task and muscle dependent.

PMID- 19164777
TI  - Making room for protein in approaches to muscle recovery from endurance exercise.

PMID- 19164778
TI  - Does hypoxic vasoconstriction influence the normal distribution of human
      pulmonary blood flow?

PMID- 19164780
TI  - Frequency and outcome of carotid atheromatous disease in patients with stroke in
      Pakistan.
AB  - BACKGROUND AND PURPOSE: Limited data exist on the frequency and outcome of
      carotid artery disease in Pakistan. Such information would help guide the
      usefulness of screening for the condition in this low-middle income health care
      setting. METHODS: A prospective, descriptive study was conducted among 3 large
      teaching hospitals in Karachi, Pakistan. Patients referred for carotid Doppler
      ultrasound examination were included if they had experienced a stroke or TIA
      within the previous month. The severity and morphology of carotid disease were
      characterized by trained technicians using standardized criteria. Demographic and
      risk factor data were collected at baseline, and the outcome of patients was
      assessed at least 6 months later. RESULTS: A total of 672 patients underwent
      bilateral carotid Doppler ultrasound (1344 carotid examinations). The findings
      revealed 0% to 50% stenosis in 526 (78%), 51% to 69% stenosis in 57 (8%), 70% to
      99% stenosis in 82 (12%), and total occlusion in 7 patients (1%). Potentially
      surgically correctable disease, defined as 70% to 99% carotid artery stenosis,
      was present in only 79 (12%) patients, of whom 47 (60%) were ipsilateral
      symptomatic, 15 (20%) asymptomatic, and 17 (20%) had status unknown. Outcome
      information at >or=6 months follow-up was available for 36 of the 47 (76%)
      surgically correctable and only 4 of these patients (12%) had undergone surgical
      or radiological intervention (carotid endarterectomy in 3 patients and carotid
      stenting in 1 patient). CONCLUSIONS: The frequency of carotid artery disease of
      at least moderate severity is very low in patients with recent stroke or TIA and
      there is low utilization of high-cost, carotid intervention procedures in
      Pakistan. These data raise questions regarding the applicability and cost
      effectiveness of routine carotid ultrasound screening in our country and similar
      population in Asia. The local socio-economic and clinical data do not support
      routine carotid Doppler ultrasound in every patient with stroke and TIA in
      Pakistan. Studies are warranted to determine predictors of significant carotid
      artery stenosis in stroke/TIA patients of our country to develop reliable stroke
      guidelines appropriate for local population.

PMID- 19164779
TI  - Roles of glia limitans astrocytes and carbon monoxide in adenosine diphosphate
      induced pial arteriolar dilation in newborn pigs.
AB  - BACKGROUND AND PURPOSE: Astrocytes, neurons, and microvessels together form a
      neurovascular unit allowing blood flow to match neuronal activity. Adenosine
      diphosphate (ADP) is an important signaling molecule in the brain, and dilation
      in response to ADP is astrocyte-dependent in rats and newborn pigs. Carbon
      monoxide (CO), produced endogenously by catabolism of heme to CO, iron, and
      biliverdin via heme oxygenase, is an important cell-signaling molecule in the
      neonatal cerebral circulation. We hypothesize ADP stimulates CO production by
      glia limitans astrocytes and that this CO causes pial arteriolar dilation.
      METHODS: Experiments were performed using anesthetized piglet with closed cranial
      windows, and freshly isolated piglet astrocytes and microvessels. Astrocyte
      injury was caused by topical application of L-2-alpha aminoadipic acid (2 mmol/L,
      5 hours). Cerebrospinal fluid was collected from under the cranial windows for
      measurement of ADP-stimulated CO production. CO was measured by gas
      chromatography-mass spectroscopy analysis. RESULTS: Before, but not after,
      astrocyte injury in vivo, topical ADP stimulated both CO production and dilation
      of pial arterioles. Astrocyte injury did not block dilation to isoproterenol or
      bradykinin. Chromium mesoporphyrin, an inhibitor of heme oxygenase, also
      prevented the ADP-induced increase in cerebrospinal fluid CO and pial arteriolar
      dilation caused by ADP, but not dilation to sodium nitroprusside. ADP also
      increased CO production by freshly isolated piglet astrocytes and cerebral
      microvessels, although the increase was smaller in the microvessels. CONCLUSIONS:
      These data suggest that glia limitans astrocytes use CO as a gasotransmitter to
      cause pial arteriolar dilation in response to ADP.

PMID- 19164781
TI  - Impact of monocyte chemoattractant protein-1 deficiency on cerebral aneurysm
      formation.
AB  - BACKGROUND AND PURPOSE: Recent studies have suggested that chronic inflammation
      actively participates in cerebral aneurysm (CA) formation. Macrophages accumulate
      in CA walls and express proinflammatory genes promoting CA progression, but the
      molecular mechanisms of monocyte/macrophage recruitment into CA walls remain to
      be elucidated. METHODS: Monocyte chemoattractant protein-1 (MCP-1) expression in
      experimentally induced CAs was assessed by immunohistochemistry and Western
      blotting. The role of MCP-1 in CA formation was examined by MCP-1(-/-) mice and a
      plasmid DNA encoding a dominant negative mutant of MCP-1 (7ND). MCP-1 expression
      in human CAs was examined by immunohistochemistry. RESULTS: MCP-1 expression was
      upregulated in aneurysmal walls at the early stage of CA formation. MCP-1(-/-)
      mice exhibited a significant decrease of CA formation and macrophage accumulation
      with decreased expression of matrix metalloproteinase-2, -9, and inducible nitric
      oxide synthase. Immunohistochemistry for the DNA binding form of nuclear factor
      kappa B showed nuclear factor-kappa B activation in MCP-1-expressing cells.
      Blockade of MCP-1 activity by 7ND resulted in the inhibition of CA progression in
      rats. In human CAs, MCP-1 was also expressed in CA walls. CONCLUSIONS: These data
      suggest that MCP-1 plays a crucial role in CA formation as a major
      chemoattractant for monocyte/macrophage. MCP-1 expression in CA walls is induced
      through nuclear factor-kappa B activation. MCP-1 may be a novel therapeutic
      target of medical treatment preventing CA progression.

PMID- 19164782
TI  - Treating visual speech perception to improve speech production in nonfluent
      aphasia.
AB  - BACKGROUND AND PURPOSE: Several recent studies have revealed modulation of the
      left frontal lobe speech areas not only during speech production but also for
      speech perception. Crucially, the frontal lobe areas highlighted in these studies
      are the same ones that are involved in nonfluent aphasia. Based on these
      findings, this study examined the utility of targeting visual speech perception
      to improve speech production in nonfluent aphasia. METHODS: Ten patients with
      chronic nonfluent aphasia underwent computerized language treatment utilizing
      picture-word matching. To examine the effect of visual speech perception on
      picture naming, 2 treatment phases were compared-one that included matching
      pictures to heard words and another in which pictures were matched to heard words
      accompanied by a video of the speaker's mouth presented on the computer screen.
      RESULTS: The results revealed significantly improved picture naming of both
      trained and untrained items after treatment when it included a visual speech
      component (ie, seeing the speaker's mouth). In contrast, the treatment phase in
      which pictures were only matched to heard words did not result in statistically
      significant improvement of picture naming. CONCLUSIONS: The findings suggest that
      focusing on visual speech perception can significantly improve speech production
      in nonfluent aphasia and may provide an alternative approach to treat a disorder
      in which speech production seldom improves much in the chronic phase of stroke.

PMID- 19164783
TI  - Monocytes are major players in the prognosis and risk of infection after acute
      stroke.
AB  - BACKGROUND AND PURPOSE: Monocytes participate in adaptive and innate immune
      responses. Monocyte numbers increase in patients with stroke associated infection
      (SAI) or severe stroke. Whether changes in monocytes are related to specific
      effects, or simply mark brain damage, remains unsettled. METHODS: We used flow
      cytometry in 45 consecutive strokes and 12 healthy controls to assess the time
      course of monocytes, their phenotype, and the production of cytokines after
      stimulation. Cortisol, TNF-alpha, IFN-gamma, and IL-10 were measured in serum and
      metanephrine in plasma. The effects of humoral and cellular parameters on the
      risk of SAI and poor outcome were tested in multivariate analyses adjusted for
      confounders (NIHSS score, age, and tube feeding). RESULTS: Surface expression of
      human leukocyte antigen-DR, Toll-like receptor-2, and production of TNF-alpha in
      monocytes were independently associated with stroke. Distinct immune mechanisms
      were related with functional outcome and the risk of SAI; the signature of SAI
      included an increase of cortisol, metanephrine, and IL-10 in serum, and reduced
      production of TNF-alpha in monocytes; poor outcome was associated with increased
      expression of Toll-like receptor-4 in monocytes (OR, 9.61; 95% CI, 1.27-72.47).
      SAI did not predict poor outcome (OR, 5.63; 95% CI, 0.45-70.42; P=0.18).
      CONCLUSIONS: In human stroke, poor outcome is associated to innate responses
      mediated by Toll-like receptor-4 in monocytes. SAI may result from the
      immunosuppressive and antiinflammatory effects of corticoids, catecholamines, IL
      10, and deactivated monocytes. Early treated SAI does not contribute
      significantly to additional brain damage. These findings encourage the
      exploration of strategies aimed to inhibit Toll-like receptor-4 signaling in
      acute stroke.

PMID- 19164784
TI  - Are unadjusted analyses of clinical trials inappropriately biased toward the
      null?

PMID- 19164785
TI  - Anoxia-induced NF-kappaB-dependent upregulation of NCX1 contributes to Ca2+
      refilling into endoplasmic reticulum in cortical neurons.
AB  - BACKGROUND AND PURPOSE: The 3 gene products of the Na(+)/Ca(2+) exchanger (NCX),
      viz, NCX1, NCX2, and NCX3, may play a pivotal role in the pathophysiology of
      brain ischemia. The aim of this study was to investigate the transductional and
      posttranslational mechanisms involved in the expression of these isoforms during
      oxygen and glucose deprivation and their role in endoplasmic reticulum Ca(2+)
      refilling in cortical neurons. METHODS: NCX1, NCX2, and NCX3 transcript and
      protein expression was evaluated in primary cortical neurons by reverse
      transcriptase-polymerase chain reaction and Western blot. NCX currents (I(NCX))
      and cytosolic Ca(2+) concentrations ([Ca(2+)](i)) were monitored by means of
      patch-clamp in whole-cell configuration and Fura-2AM single-cell video imaging,
      respectively. RESULTS: Exposure of cortical neurons to 3 hours of oxygen and
      glucose deprivation yielded dissimilar effects on the 3 isoforms. First, it
      induced an upregulation in NCX1 transcript and protein expression. This change
      was exerted at the transcriptional level because the inhibition of nuclear factor
      kappa B translocation by small interfering RNA against p65 and SN-50 prevented
      oxygen and glucose deprivation-induced NCX1 upregulation. Second, it elicited a
      downregulation of NCX3 protein expression. This change, unlike NCX1, was exerted
      at the posttranscriptional level because it was prevented by the proteasome
      inhibitor MG-132. Finally, we found that it significantly increased I(NCX) both
      in the forward and reverse modes of operation and promoted an increase in ER
      Ca(2+) accumulation. Interestingly, such accumulation was prevented by the
      silencing of NCX1 and the NCX inhibitor CB-DMB that triggered caspase-12
      activation. CONCLUSIONS: These results suggest that nuclear factor kappa B
      dependent NCX1 upregulation may play a fundamental role in Ca(2+) refilling in
      the endoplasmic reticulum, thus helping neurons to prevent endoplasmic reticulum
      stress during oxygen and glucose deprivation.

PMID- 19164786
TI  - Brain-derived neurotrophic factor contributes to recovery of skilled reaching
      after focal ischemia in rats.
AB  - BACKGROUND AND PURPOSE: Brain-derived neurotrophic factor (BDNF) is involved in
      neuronal survival, synaptic plasticity, learning and memory, and neuroplasticity.
      Further, exogenous treatment with BDNF or exposing animals to enrichment and
      exercise regimens, which also increase BDNF, enhances behavioral recovery after
      brain injury. Thus, the beneficial effects of rehabilitation in promoting
      recovery after stroke may also depend on BDNF. We tested this hypothesis by
      evaluating the contribution of BDNF to motor skill relearning after endothelin-1
      induced middle cerebral artery occlusion in rats. METHODS: Antisense BDNF
      oligonucleotide, which blocks the expression of BDNF (or saline vehicle) was
      infused into the contralateral lateral ventricle for 28 days after ischemia.
      Animals received either a graduated rehabilitation program, including running
      exercise and skilled reaching training, which simulates clinical practice, or no
      rehabilitation. Functional recovery was assessed with a battery of tests that
      measured skilled reaching, forelimb use asymmetry, and foraging ability. RESULTS:
      Rehabilitation significantly improved skilled reaching ability in the staircase
      task. Antisense BDNF oligonucleotide effectively blocked BDNF mRNA, and negated
      the beneficial effects of rehabilitation on recovery of skilled reaching.
      Importantly, antisense BDNF oligonucleotide did not affect reaching with the
      unaffected limb, body weight, infarct size, or foraging ability, indicating the
      treatment was specific to relearning of motor skill after ischemia. CONCLUSIONS:
      This study is the first to identify a critical role for BDNF in rehabilitation
      induced recovery after stroke, and our results suggest that new treatments to
      enhance BDNF would constitute a promising therapy for promoting recovery of
      function after stroke.

PMID- 19164787
TI  - Danqi Piantang Jiaonang (DJ), a traditional Chinese medicine, in poststroke
      recovery.
AB  - BACKGROUND AND PURPOSE: Stroke is a leading cause of death and disability
      worldwide. Despite improvements in acute stroke treatment, many patients only
      make a partial or poor recovery. Therefore, there is a need for treatments that
      would further improve outcome. Danqi Piantang Jiaonang (DJ; NeuroAid), a
      traditional Chinese medicine widely used in China to improve recovery after
      stroke, has been compared with another traditional Chinese medicine in 2
      unpublished randomized clinical trials. The results of these studies were pooled
      and reanalyzed to assess efficacy and safety. METHODS: Six hundred five subjects
      were randomized in 2 randomized double-blinded, controlled trials to receive
      either DJ or Buchang Naoxintong Jiaonang. Subjects were treated for 1 month.
      Inclusion criteria were: (1) patients with recent (from 10 days to 6 months)
      ischemic stroke; (2) patients satisfying Western diagnostic standards for stroke
      and traditional Chinese medicine standards for diagnosis of apoplexy; and (3)
      Diagnostic Therapeutic Effects of Apoplexy score >/=10. RESULTS: The functional
      outcome, measured by the Comprehensive Function Score component of the Diagnostic
      Therapeutic Effects of Apoplexy scale, showed a statistically significant
      superiority of DJ over the control treatment group (relative risk, 2.4; 95% CI,
      1.28 to 4.51; P=0.007). Tolerance was excellent in both groups. CONCLUSIONS: The
      pooled analysis of 2 unpublished trials of DJ, a traditional Chinese medicine
      currently approved in China to improve neurological recovery after stroke, shows
      good tolerability and superiority of DJ over another traditional Chinese medicine
      also approved for stroke. A large double-blind randomized clinical trial is
      required to further assess the safety and efficacy of DJ.

PMID- 19164789
TI  - Regional white matter integrity differentiates between vascular dementia and
      Alzheimer disease.
AB  - BACKGROUND AND PURPOSE: Considerable clinical and radiological overlap between
      vascular dementia (VaD) and Alzheimer disease (AD) often makes the diagnosis
      difficult. Diffusion-tensor imaging studies showed that fractional anisotropy
      (FA) could be a useful marker for white matter changes. This study aimed to
      identify regional FA changes to identify a biomarker that could be used to
      differentiate VaD from AD. METHODS: T1-weighted and diffusion-tensor imaging
      scans were obtained in 13 VaD patients, 16 AD patients, and 22 healthy elderly
      controls. We used tract-based spatial statistics to study regional changes in
      fractional anisotropy in AD, VaD, and elderly controls. We then used
      probabilistic tractography to parcel the corpus callosum in 7 regions according
      to its connectivity with major cerebral cortices using diffusion-tensor imaging
      data set. We compared the volume and mean FA in each set of transcallosal fibers
      between groups using ANOVA and then applied a discriminant analysis based on FA
      and T2-weighted imaging measures. RESULTS: FA reduction in forceps minor was the
      most significant area of difference between AD and VaD. Segmentation of the
      corpus callosum using tractography and comparison of FA changes of each segment
      confirmed the FA changes in transcallosal prefrontal tracts of patients with VaD
      when compared to AD. The best discriminant model was the combination of
      transcallosal prefrontal FA and Fazekas score with 87.5% accuracy, 100%
      specificity, and 93% sensitivity (P<0.0001). CONCLUSIONS: Integrating mean FA in
      the forceps minor to the Fazekas score provides a useful quantitative marker for
      differentiating AD from VaD.

PMID- 19164790
TI  - Thrombolysis in stroke mimics: frequency, clinical characteristics, and outcome.
AB  - BACKGROUND AND PURPOSE: Intravenous thrombolysis for acute ischemic stroke is
      usually based on clinical assessment, blood test results, and CT findings.
      Intravenous thrombolysis of stroke mimics may occur but has not been studied in
      detail. METHODS: We determined frequency, clinical characteristics, and outcome
      of mimic patients versus patients with stroke treated with intravenous
      thrombolysis using data of a prospective, single-center thrombolysis data bank.
      RESULTS: Among 250 patients, 243 (97.2%) had strokes and 7 (2.8%) were mimics.
      Seizure was the most frequent diagnosis among mimics. There was a trend toward
      lower National Institutes of Health Stroke Scale scores in mimics (9.9+/-4.2)
      compared with strokes (13.7+/-5.4; P=0.06). Global aphasia without hemiparesis
      was the presenting symptom in 3 (42.9%) mimics versus 8 (3.3%) strokes (P=0.002).
      Orolingual angioedema, symptomatic intracranial hemorrhage, and asymptomatic
      intracranial hemorrhage occurred in 3 (1.2%), 13 (5.3%), and 30 (12.3%) patients
      with stroke, but were absent in mimics. After 3 months, 6 (85.7%) mimics and 86
      (35.4%) strokes had a modified Rankin Scale score of 0 to 1 (P=0.01).
      CONCLUSIONS: Only few patients receiving intravenous thrombolysis did eventually
      have a final diagnosis other than stroke, ie, mostly seizures. Their outcome was
      favorable. Although clinical features differed between the stroke and the mimic
      groups, the differences were not distinctive enough to allow assigning individual
      patients to either of the groups. Multimodal neuroimaging or
      electroencephalographic recordings may be helpful for this assignment. However,
      their potential benefit has to be weighed against the potential harm of delayed
      thrombolysis.

PMID- 19164791
TI  - Quantitative magnetic resonance angiography: a promising tool in the assessment
      of intracranial in-stent stenosis?

PMID- 19164788
TI  - Randomized, double-blinded, placebo controlled study of neuroprotection with
      lidocaine in cardiac surgery.
AB  - BACKGROUND AND PURPOSE: Cognitive decline after cardiac surgery remains common
      and diminishes patients' quality of life. Based on experimental and clinical
      evidence, this study assessed the potential of intravenously administered
      lidocaine to reduce postoperative cognitive dysfunction after cardiac surgery
      using cardiopulmonary bypass. METHODS: After IRB approval, 277 patients
      undergoing cardiac surgery were enrolled into this prospective, randomized,
      double-blinded placebo controlled clinical trial. Subjects were randomized to
      receive: (1) Lidocaine as a 1 mg/kg bolus followed by a continuous infusion
      through 48 hours postoperatively, or (2) Placebo bolus and infusion. Cognitive
      function was assessed preoperatively and again at 6 weeks and 1 year
      postoperatively. The effect of lidocaine on postoperative cognition was tested
      using multivariable regression modeling; P<0.05 was considered significant.
      RESULTS: Among the 241 allocated subjects (Lidocaine: n=114; Placebo: n=127), the
      incidence of cognitive deficit in the lidocaine group was 45.5% versus 45.7% in
      the placebo group (P=0.97). Multivariable analysis revealed a significant
      interaction between treatment group and diabetes, such that diabetic subjects
      receiving lidocaine were more likely to suffer cognitive decline (P=0.004).
      Secondary analysis identified total lidocaine dose (mg/kg) as a significant
      predictor of cognitive decline and also revealed a protective effect of lower
      dose lidocaine in nondiabetic subjects. CONCLUSIONS: Lidocaine administered
      during and after cardiac surgery does not reduce the high rate of postoperative
      cognitive dysfunction. Higher doses of lidocaine and diabetic status were
      independent predictors of cognitive decline. Protective effects of lower dose
      lidocaine in nondiabetic subjects need to be further evaluated.

PMID- 19164792
TI  - Gender-related differences in diagnostic evaluation and outcome of ischemic
      stroke in Poland.
AB  - BACKGROUND AND PURPOSE: We compared the diagnostic evaluation and outcome of
      ischemic stroke between men and women in large cohort of Polish patients.
      METHODS: Our study included 1488 consecutive patients (755 women and 733 men)
      with ischemic stroke, treated in a single stroke unit between January 2002 and
      August 2007. We analyzed demographic factors, major risk factors for stroke,
      severity of neurological deficit on admission, diagnostic work-up performed
      during the hospital stay, and outcome on discharge. RESULTS: Women were older
      than men (70.9+/-13.7 vs 66.2+/-12.7 years; P<0.001) and had greater neurological
      deficit on admission (median NIHSS score: 7 [3-13] vs 5 [3-10]; P<0.001). They
      were also less likely to obtain good recovery on discharge (39.2% vs 49.9%;
      P<0.001). Carotid ultrasound and echocardiography were performed more often in
      men (77.2% vs 68.7% and 52.4% vs 46.5%, respectively; P<0.05). Lesser
      neurological deficit on admission, younger age, and lack of history of myocardial
      infarction or previous stroke, but not gender, were independent predictors of
      full diagnostic work-up. CONCLUSIONS: Gender does not influence the adequate
      diagnostic evaluation of ischemic stroke as an independent factor.

PMID- 19164793
TI  - Impact of prehypertension on common carotid artery intima-media thickness and
      left ventricular mass.
AB  - BACKGROUND AND PURPOSE: Prehypertension has been recently introduced by JNC 7 as
      a new blood pressure (BP) category, associated with increased target-organ
      damage. Subclinical atherosclerosis by means of common artery intima-media
      thickness (CCA-IMT) has been incompletely investigated in prehypertensive
      patients. The aim of our study was to assess the extent of CCA-IMT and left
      ventricular mass (LVM) in prehypertensive adults in comparison to normotensive
      and untreated hypertensive subjects. METHODS: From a total of 5221 consecutive
      patients screened to our Hypertension Unit we selected 896 consecutive
      individuals according to prespecified inclusion criteria, who underwent 24-hour
      ambulatory BP monitoring, carotid artery ultrasonographic, and echocardiographic
      measurements. Patients who received antihypertensive treatment during the BP
      monitoring were excluded. According to the office BP levels, patients were
      divided into 3 subgroups: normotensives (office BP <120/80 mm Hg),
      prehypertensives (120/80 mm Hg<or=office BP<140/90 mm Hg), and hypertensives
      (office BP >or=140/90 mm Hg). Statistical analyses were performed by means of 1
      way ANOVA, chi(2) test, and ANCOVA. RESULTS: According to the office BP levels,
      the distribution of the study population was: normotensives (14.4%),
      prehypertensives (23.7%), and hypertensives (61.9%). Prehypertensive patients had
      higher CCA-IMT (P=0.038) and LVM (P=0.030) values than normotensive subjects,
      even after adjustment for baseline characteristics. Greater CCA-IMT values were
      observed in hypertensive patients in comparison to prehypertensives (P=0.002).
      CONCLUSIONS: Prehypertensive patients had higher CCA-IMT and LVM than their
      normotensive counterparts. Prehypertension status is cross-sectionally associated
      with subclinical atherosclerosis and target-organ damage.

PMID- 19164794
TI  - Elevated C-reactive protein and long-term mortality after ischaemic stroke:
      relationship with markers of endothelial cell and platelet activation.
AB  - BACKGROUND AND PURPOSE: Inflammatory biomarkers predict development of
      atherothrombotic events. In the present study we examined the relationships
      between C-reactive protein (CRP), complement C3, and long-term mortality after
      acute ischemic stroke. METHODS: CRP and C3 were analyzed by in-house enzyme
      linked immunosorbent assay in 394 subjects with acute ischemic stroke who
      survived for >30 days, followed-up for a median of 7.4 years. RESULTS: CRP was
      higher in subjects who died (10.8 mg/L; 95% CI, 9.1-12.8) compared with survivors
      (3.8 mg/L; 95% CI, 3.1-4.7), whereas C3 was similar in both groups (P=0.26). CRP
      remained predictive for mortality after adjusting for conventional clinical and
      demographic risk factors (the adjusted hazard ratio for those with CRP in the
      highest compared with the lowest quartile was 2.0; 95% CI, 1.3-3.1). However, CRP
      was no longer independently predictive of mortality after additionally adjusting
      for beta-thromboglobulin or von Willebrand factor. CONCLUSIONS: Our data suggest
      that the relationship between CRP and poststroke mortality may in part reflect
      inflammation-induced endothelial cell dysfunction and platelet activation.

PMID- 19164795
TI  - Transcranial duplex sonography for monitoring hyperacute intracerebral
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Early hematoma growth is one of the main determinants of
      mortality in patients with intracranial hemorrhage (ICH). Transcranial duplex
      sonography (TDS) might represent a useful tool for the bedside monitoring of
      early ICH enlargement. We aimed to correlate ICH volumes measured by TDS and CT
      scan in patients with ICH evaluated <3 hours of symptom onset. METHODS: We
      prospectively studied 34 patients with supratentorial ICH evaluated <3 hours of
      onset. All patients underwent emergent CT scan and TDS examination on admission
      and at 6 hours. Major longitudinal, sagittal, and coronal hematoma diameters were
      measured on CT scan by a neuroradiologist and on TDS by a blinded operator with a
      time delay <30 minutes between both techniques. Total hematoma volume was
      determined using the formula for irregular volumes
      (longitudinalxsagittalxcoronal)/2. Early hematoma growth was defined as an
      increase >20% in the hematoma volume at 6 hours. RESULTS: ICH was identified on
      TDS as an hyperechogenic mass located in the basal ganglia in 28 patients and in
      the lobar position in 6. Mean hematoma volume at baseline was 86+/-4 5 mL. At 6
      hours, early hematoma growth was seen in 9 (26%) patients. An excellent
      correlation was found between TDS and CT measurements for all diameters:
      longitudinal (r=0.91, P<0.001), sagittal (r=0.85, P=0.002), coronal (r=0.79,
      P=0.022) and for total hematoma volume (r=0.82, P=0.001). When all obtained
      measures were matched, the intraclass correlation coefficient was 0.888 (95% CI,
      0.8 to 0.937). CONCLUSIONS: TDS showed an excellent correlation with CT in
      measuring the extent of bleeding in patients with hyperacute ICH. TDS may
      represent a reliable useful tool for monitoring ICH noninvasively at the
      patient's bedside.

PMID- 19164796
TI  - Prevalence of abnormal glucose metabolism and insulin resistance among subtypes
      of ischemic stroke in Japanese patients.
AB  - BACKGROUND AND PURPOSE: The purpose was to assess the prevalence of disorders of
      glucose metabolism and insulin resistance in Japanese ischemic stroke patients
      with no history of diabetes by performing 75-gram oral glucose tolerance test
      (OGTT). METHODS: We recruited 427 ischemic stroke patients (atherothrombotic
      infarction, n=220; lacunar infarction, n=125; cardioembolic infarction, n=82).
      OGTT was used to evaluate disorders of glucose metabolism in stroke patients
      without previously known diabetes (n=113). We investigated the relationships
      among the prevalence of abnormal glucose metabolism, ischemic stroke subtypes,
      and the prevalence of insulin resistance using homeostasis model assessment for
      insulin resistance and immunoreactive insulin at 120 minutes after glucose
      loading (IRI(120)). RESULTS: OGTT identified the presence of disorders of glucose
      metabolism in 62.8% of ischemic stroke patients without previously known
      diabetes, including diabetes (24.8%) and impaired glucose tolerance (lone
      impaired glucose tolerance and impaired fasting glucose plus impaired glucose
      tolerance, 34.5%). The prevalence of newly diagnosed diabetes and impaired
      glucose tolerance was the highest in the atherothrombotic infarction group
      (68.9%). The highest values of homeostasis model assessment for insulin
      resistance and immunoreactive insulin at 120 minutes after glucose loading were
      found in atherothrombotic infarction patients with abnormal glucose tolerance.
      CONCLUSIONS: In this study, a significantly large percentage of Japanese patients
      with ischemic stroke and no history of diabetes were found to have disorders of
      glucose metabolism by OGTT. Impaired glucose tolerance and insulin resistance
      could play an important pathogenic role in the development of atherothrombotic
      infarction.

PMID- 19164797
TI  - The utility of quantitative magnetic resonance angiography in the assessment of
      intracranial in-stent stenosis.
AB  - BACKGROUND AND PURPOSE: Noninvasive screening for intracranial in-stent stenosis
      is often limited by artifact because of the stent or associated coils. We aimed
      to determine the utility of quantitative MRA (QMRA) as a screening tool for
      detecting intracranial in-stent stenosis. METHODS: We reviewed 14 patients who
      had intracranial stent placement with follow-up QMRA and conventional angiography
      at our institution. Socio-demographic, medical, clinical, and imaging data were
      abstracted from medical charts. A blinded interventional neurologist reviewed all
      angiograms for presence of >50% in-stent stenosis. We tested QMRA (mL/min) at
      varying thresholds as a predictor of angiographic results. RESULTS: Among 14
      patients (mean age, 62 years; 12 female, 2 male), 13 patients had Neuroform
      stents placed for wide-neck cerebral aneurysms and 1 patient had a Wingspan stent
      placement for atherosclerotic stenosis. Lesions were located in the intracranial
      internal carotid artery in 57.2% (n=8), the middle cerebral artery in 14.3%
      (n=2), and vertebrobasilar arteries in 28.6% (n=4). On follow-up angiography, 2
      patients (14.3%) had >50% in-stent stenosis on angiography. Time-of-flight MRA
      was nondiagnostic in each case because of artifact from the stent or coils. A
      >20% reduction in vessel-specific blood flow by QMRA was associated with presence
      of >50% in-stent stenosis on angiography (P=0.033). As a screening tool to
      predict >50% angiographic in-stent stenosis, the sensitivity, specificity,
      positive predictive value, and negative predictive value of QMRA were 100%, 92%,
      67%, and 100%, respectively. CONCLUSIONS: We found that QMRA is a promising
      screening tool to detect intracranial in-stent stenosis. Future prospective
      studies should focus on whether QMRA has a role in the detection of radiographic
      restenosis and prediction of clinical events.

PMID- 19164798
TI  - Should stroke trials adjust functional outcome for baseline prognostic factors?
AB  - BACKGROUND AND PURPOSE: Many stroke trials have provided neutral results.
      Suboptimal statistical analyses may be failing to detect effective interventions.
      Adjusting outcomes for baseline prognostic factors in the analysis may improve
      the efficiency of analysis of outcomes. METHODS: Data from 23 stroke trials (25
      674 patients) assessing functional outcome were included. The prognostic
      variables considered were age, sex, and baseline severity. Unadjusted and
      adjusted ordinal logistic regression models were compared using simulated data
      from each trial (10 000 simulations per trial). Three levels of treatment effect
      were assessed with ORs of 0.95, 0.74, and 0.57. The reduction in sample size
      gained from using the adjusted models, as compared with an unadjusted model, was
      then calculated as a reflection of the increase in statistical power. RESULTS:
      Adjusting outcome for baseline factors led to a reduction in sample size, which
      was similar across all 3 treatment effects (median percentage reduction,
      interquartile range): OR=0.95: 35.3% (21.0 to 42.1); OR=0.74: 38.4% (29.4 to
      42.7); and OR=0.57: 38.4% (27.4 to 42.2). As the treatment effect increased, the
      proportion of simulations in which the treatment effect for the adjusted model
      was greater than for the unadjusted model also increased. CONCLUSIONS: Adjusting
      for prognostic factors in stroke trials can reduce sample size by at least 20% to
      30% (the lower interquartile range) for a given power. Conversely, trialists may
      want to power for an unadjusted analysis and then increase statistical power by
      adjusting for prognostic factors.

PMID- 19164799
TI  - Which reported estimate of the prevalence of malnutrition after stroke is valid?
AB  - BACKGROUND AND PURPOSE: The reported prevalence of malnutrition after stroke
      varies widely, whereas it remains unclear which of the estimates is most
      accurate. The aim of this review was to explore possible sources of this
      heterogeneity among studies and to evaluate whether the nutritional assessment
      techniques used were valid. METHODS: A literature search was conducted to
      identify all studies in which the nutritional state of patients was assessed
      after inpatient admission for stroke. The percentages of patients identified as
      malnourished in each study and method of nutritional assessment are reported. For
      the purposes of this study, an assessment technique was considered valid if at
      least one form of validity had been demonstrated previously through psychometric
      evaluation. RESULTS: Eighteen studies meeting inclusion criteria were identified.
      The reported frequency of malnutrition ranged from 6.1% to 62%. Seventeen
      different methods of nutritional assessment were used. Four trials used
      previously validated assessment methods: Subjective Global Assessment, "an
      informal assessment," and Mini Nutritional Assessment. The nutritional assessment
      methods used in the remaining studies used had not been validated previously.
      CONCLUSIONS: The use of a wide assortment of nutritional assessment tools, many
      of which have not been validated, may have contributed to the wide range of
      estimates of malnutrition. If so, this underscores the need for valid and
      reliable assessment tools to further our understanding of the relationship
      between stroke and nutritional status.

PMID- 19164800
TI  - Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement
      for healthcare professionals from a special writing group of the Stroke Council,
      American Heart Association.

PMID- 19164801
TI  - Soluble Flt-1 gene transfer ameliorates neointima formation after wire injury in
      flt-1 tyrosine kinase-deficient mice.
AB  - OBJECTIVE: We have demonstrated that vascular endothelial growth factor (VEGF)
      expression is upregulated in injured vascular wall, and blockade of VEGF
      inhibited monocyte infiltration and neointima formation in several animal models.
      In the present study, we aimed to clarify relative role of two VEGF receptors,
      flt-1 versus flk-1/KDR, in neointima formation after injury using flt-1 tyrosine
      kinase-deficient (Flt-1 TK(-/-)) mice and soluble Flt-1(sFlt-1) gene transfer.
      METHODS AND RESULTS: Neointima formation was comparable between wild-type and Flt
      1 TK(-/-) mice 28 days after intraluminal wire injury in femoral arteries. By
      contrast, neointima formation was significantly suppressed by sFlt-1 gene
      transfer into Flt-1 TK(-/-) mice that blocks VEGF action on flk-1 (intima/media
      ratio: 2.8+/-0.4 versus 1.4+/-0.4, P<0.05). The inhibition of neointima formation
      was preceded by significant reduction of monocyte chemoattractant protein (MCP-1)
      expression in vascular smooth muscle cells (VSMCs) and monocyte infiltration 7
      days after injury. Gene transfer of sFlt-1 or treatment of flk-1-specific
      antibody significantly inhibited VEGF-induced MCP-1 expression determined by RT
      PCR in cultured aortic tissue and VSMCs. MCP-1-induced chemotaxis was equivalent
      between wild-type and Flt-1 TK(-/-) mice. CONCLUSIONS: These results suggest that
      endogenous VEGF accelerates neointima formation through flk-1 by regulating MCP-1
      expression in VSMCs and macrophage-mediated inflammation in injured vascular wall
      in murine model of wire injury.

PMID- 19164802
TI  - Arginase promotes neointima formation in rat injured carotid arteries.
AB  - OBJECTIVE: Arginase stimulates the proliferation of cultured vascular smooth
      muscle cells (VSMCs); however, the influence of arginase on VSMC growth in vivo
      is not known. This study investigated the impact of arginase on cell cycle
      progression and neointima formation after experimental arterial injury. METHODS
      AND RESULTS: Balloon injury of rat carotid arteries resulted in a sustained
      increase in arginase activity in the vessel wall and the induction of arginase I
      protein in both the media and neointima of injured vessels. Furthermore, local
      perivascular application of the potent and selective arginase inhibitors S-(2
      boronoethyl)-L-cysteine (BEC) or N(G)-hydroxy-nor-L-arginine (L-OHNA) immediately
      after injury markedly attenuated medial and neointimal DNA synthesis and
      neointima formation. Substantial arginase I protein and arginase activity was
      also detected in rat cultured aortic VSMCs. Moreover, treatment of VSMCs with BEC
      or L-OHNA, or knockdown of arginase I protein, arrested cells in the G(0)/G(1)
      phase of the cell cycle and induced the expression of the cyclin-dependent
      protein kinase inhibitor, p21. CONCLUSIONS: This study demonstrates that arginase
      is essential for VSMCs to enter the cell cycle and that arginase I contributes to
      the remodeling response after arterial injury. Arginase I represents a
      potentially new therapeutic target for the treatment of vasculoproliferative
      disorders.

PMID- 19164803
TI  - The capacity of group V sPLA2 to increase atherogenicity of ApoE-/- and LDLR-/-
      mouse LDL in vitro predicts its atherogenic role in vivo.
AB  - OBJECTIVE: In vitro data indicate that human LDL modified by Group V secretory
      phospholipase A(2) (GV sPLA(2)) is proatherogenic. Consistent with this, gain and
      loss of function studies demonstrated that GV sPLA(2) promotes atherosclerosis in
      LDLR(-/-) mice. The current study investigates whether GV sPLA(2) promotes
      atherosclerotic processes in apoE(-/-) mice. METHODS AND RESULTS: LDL (d=1.019 to
      1.063) from apoE(-/-) and LDLR(-/-) mice fed chow or Western diet were hydrolyzed
      by GV sPLA(2). Phosphatidylcholine on LDL from LDLR(-/-) mice fed either a chow
      or Western diet was hydrolyzed to a greater extent (61.1+/-0.4% and 45.3+/-4.6%)
      than the corresponding fractions from apoE(-/-) mice (41.7+/-3.6% and 39.4+/
      1.2%). ApoE(-/-) LDL induced macrophage foam cell formation in vitro without
      modification by GV sPLA(2), whereas hydrolysis of LDLR(-/-) LDL was a
      prerequisite for foam cell formation. In contrast to findings in LDLR(-/-) mice,
      GV sPLA(2) deficiency did not significantly reduce atherosclerosis in apoE(-/-)
      mice, although collagen content was significantly reduced in lesions of apoE(-/-)
      mice lacking GV sPLA(2). CONCLUSIONS: The ability of GV sPLA(2) to promote
      atherosclerotic lipid deposition in apoE(-/-) and LDLR(-/-) mice may be related
      to its ability to increase the atherogenic potential of LDL from these mice as
      assessed in vitro.

PMID- 19164804
TI  - Critical role of tissue kallikrein in vessel formation and maturation:
      implications for therapeutic revascularization.
AB  - OBJECTIVE: Human Tissue Kallikrein (hKLK1) overexpression promotes an enduring
      neovascularization of ischemic tissue, yet the cellular mechanisms of hKLK1
      induced arteriogenesis remain unknown. Furthermore, no previous study has
      compared the angiogenic potency of hKLK1, with its loss of function polymorphic
      variant, rs5515 (R53H), which possesses reduced kinin-forming activity. METHODS
      AND RESULTS: Here, we demonstrate that tissue kallikrein knockout mice (KLK1-/-)
      show impaired muscle neovascularization in response to hindlimb ischemia. Gene
      transfer of wild-type Ad.hKLK1 but not Ad.R53H-hKLK1 was able to rescue this
      defect. Similarly, in the rat mesenteric assay, Ad.hKLK1 induced a mature
      neovasculature with increased vessel diameter through kinin-B2 receptor-mediated
      recruitment of pericytes and vascular smooth muscle cells, whereas Ad.R53H-hKLK1
      was ineffective. Moreover, hKLK1 but not R53H-hKLK1 overexpression in the
      zebrafish induced endothelial precursor cell migration and vascular remodeling.
      Furthermore, Ad.hKLK1 activates metalloproteinase (MMP) activity in normoperfused
      muscle and fails to promote reparative neovascularization in ischemic MMP9-/-
      mice, whereas its proarteriogenic action was preserved in ApoE-/- mice, an
      atherosclerotic model of impaired angiogenesis. CONCLUSIONS: These results
      demonstrate the fundamental role of endogenous Tissue Kallikrein in vascular
      repair and provide novel information on the cellular and molecular mechanisms
      responsible for the robust arterialization induced by hKLK1 overexpression.

PMID- 19164805
TI  - Mechanisms targeting apolipoprotein B100 to proteasomal degradation: evidence
      that degradation is initiated by BiP binding at the N terminus and the formation
      of a p97 complex at the C terminus.
AB  - OBJECTIVE: In lipid-poor states, the ubiquitin-proteasomal pathway rapidly
      degrades misfolded apolipoprotein B100 (apoB) cotranslationally, although the
      mechanism of delivery from the ER to cytosolic proteasomes is poorly understood.
      Here we demonstrate key roles of BiP, an ER luminal chaperone, and p97, a
      cytosolic ATPase anchored to the ER membrane, in the targeting of apoB for
      proteasomal degradation. METHODS AND RESULTS: Using coimmunoprecipitations, we
      observed associations of apoB with BiP, p97, Derlin-1, VIMP, and the E3 ubiquitin
      ligase Hrd1 in HepG2 cells. BiP and p97 were found to bind apoB
      cotranslationally. Expression of C-terminal truncated apoB molecules in COS-7
      cells showed an N-terminal region outside apoB15 and a C-terminal region found in
      apoB72 were required for BiP and p97 binding, respectively. Interestingly,
      overexpression of dominant negative p97 demonstrated that the ATPase activity of
      p97 was essential for proteasomal degradation of apoB but not for apoB binding.
      However, p97 activity did not appear to affect the N terminus of apoB, which may
      be cleaved before degradation. CONCLUSIONS: These data suggest that p97 and BiP
      play critical roles in the cotranslational delivery of apoB to proteasomes and
      formation of a degradative complex. Proteasomal degradation appears to
      selectively target apoB molecules with large C-terminal domains.

PMID- 19164806
TI  - Leukotriene receptor antagonism and the prevention of extracellular matrix
      degradation during atherosclerosis and in-stent stenosis.
AB  - OBJECTIVE: The lipid-derived inflammatory mediators leukotrienes (LTs) are
      produced during vascular injury. The aim of the present study was to determine
      the role of LT receptor signaling in the pathophysiology of in-stent stenosis.
      METHODS AND RESULTS: New Zealand White rabbits were fed 0.3% cholesterol and
      subjected to angioplasty with balloon dilatation and stent implantation in the
      right carotid artery. Rabbits treated for 2 weeks with the BLT receptor
      antagonist BIIL284 (3 mg/kg once daily by oral gavage) displayed a significantly
      reduced in-stent intimal hyperplasia in carotid arteries compared with vehicle
      treated rabbits. In addition, BIIL284 treatment significantly reduced the
      extracellular matrix metalloproteinase (MMP)-2 and MMP-9 activities in stented
      arteries. The inhibited MMP-9 activity was correlated with decreased macrophage
      content in the lesions. The LTB(4)-induced migration of vascular smooth muscle
      cells was significantly inhibited by transfection with siRNA against MMP-2.
      Finally, human arteries subjected to ex vivo angioplasty and stent implantation
      displayed an increased in-stent intimal hyperplasia and higher MMP-2 and -9
      activities in the presence of LTB(4). CONCLUSIONS: These results suggest a key
      role of LT signaling in the extracellular matrix degradation associated with
      hyperlipidemia and in-stent stenosis. In conclusion, targeting LT receptors may
      represent a therapeutic strategy in atherosclerosis and interventional
      cardiology.

PMID- 19164807
TI  - The brachial artery remodels to maintain local shear stress despite the presence
      of cardiovascular risk factors.
AB  - OBJECTIVE: Under physiological conditions, arteries remodel in response to
      changes in blood flow to maintain local shear stress. Risk factors and developing
      atherosclerosis may be associated with maladaptive remodeling that produces
      relatively large arteries with low levels of shear stress. Recent studies have
      shown that the brachial artery and other peripheral arteries are enlarged in
      patients with risk factors and cardiovascular disease, and we tested the
      hypothesis that this finding represents maladaptive remodeling. METHODS AND
      RESULTS: We measured brachial artery diameter and flow by ultrasound and
      calculated shear stress in a diverse cohort of 1583 subjects (age 53+/-17 years,
      62% male, and 51% with coronary artery disease and/or peripheral arterial
      disease). In a stepwise linear regression model, age (P<0.001), gender (P<0.001),
      body mass index (P<0.001), hypertension (P=0.005), and hypercholesterolemia
      (P=0.02) were associated with larger brachial diameter. Older age was associated
      with lower shear stress (P<0.01), consistent with maladaptive remodeling.
      However, body mass index, hypertension, hypercholesterolemia, and prevalent
      atherosclerosis were associated with proportionate changes in blood flow and no
      difference in shear stress compared to reference groups, suggesting adaptive
      remodeling. CONCLUSIONS: These findings suggest that enlargement of the brachial
      artery in the setting of obesity, hypertension, hypercholesterolemia, and
      atherosclerosis reflects adaptive remodeling. The results provide further support
      for the concept that arterial remodeling is an important homeostatic response
      that is maintained despite the presence of risk factors and developing
      atherosclerosis.

PMID- 19164808
TI  - Large scale association analysis of novel genetic loci for coronary artery
      disease.
AB  - BACKGROUND: Combined analysis of 2 genome-wide association studies in cases
      enriched for family history recently identified 7 loci (on 1p13.3, 1q41, 2q36.3,
      6q25.1, 9p21, 10q11.21, and 15q22.33) that may affect risk of coronary artery
      disease (CAD). Apart from the 9p21 locus, the other loci await substantive
      replication. Furthermore, the effect of these loci on CAD risk in a broader range
      of individuals remains to be determined. METHODS AND RESULTS: We undertook
      association analysis of single nucleotide polymorphisms at each locus with CAD
      risk in 11,550 cases and 11,205 controls from 9 European studies. The 9p21.3
      locus showed unequivocal association (rs1333049, combined odds ratio [OR]=1.20,
      95% CI [1.16 to 1.25], probability value=2.81 x 10(-21)). We also confirmed
      association signals at 1p13.3 (rs599839, OR=1.13 [1.08 to 1.19], P=1.44 x 10(
      7)), 1q41 (rs3008621, OR=1.10 [1.04 to 1.17], P=1.02 x 10(-3)), and 10q11.21
      (rs501120, OR=1.11 [1.05 to 1.18], P=4.34 x 10(-4)). The associations with 6q25.1
      (rs6922269, P=0.020) and 2q36.3 (rs2943634, P=0.032) were borderline and not
      statistically significant after correction for multiple testing. The 15q22.33
      locus did not replicate. The 10q11.21 locus showed a possible sex interaction
      (P=0.015), with a significant effect in women (OR=1.29 [1.15 to 1.45], P=1.86 x
      10(-5)) but not men (OR=1.03 [0.96 to 1.11], P=0.387). There were no other strong
      interactions of any of the loci with other traditional risk factors. The loci at
      9p21, 1p13.3, 2q36.3, and 10q11.21 acted independently and cumulatively increased
      CAD risk by 15% (12% to 18%), per additional risk allele. CONCLUSIONS: The
      findings provide strong evidence for association between at least 4 genetic loci
      and CAD risk. Cumulatively, these novel loci have a significant impact on risk of
      CAD at least in European populations.

PMID- 19164809
TI  - ApoE-dependent modulation of HDL and atherosclerosis by G2A in LDL receptor
      deficient mice independent of bone marrow-derived cells.
AB  - OBJECTIVE: Deletion of the lysophospholipid-sensitive receptor, G2A, in low
      density lipoprotein receptor knockout (LDLR(-/-)) mice elevates plasma high
      density lipoprotein (HDL) cholesterol and suppresses atherosclerosis. However,
      chemotactic action of G2A in monocytes/macrophages, in addition to its modulatory
      effect on HDL, may contribute to the proatherogenic action of G2A. METHODS AND
      RESULTS: We determined that deletion of G2A in LDLR(-/-) mice increases the
      ApoA1, ApoE, and cholesterol content of plasma HDL fractions. Hepatocytes were
      shown to express G2A and hepatocytes from G2A-deficient LDLR(-/-) mice secreted
      more ApoA1 and ApoE in HDL fractions compared to their G2A-sufficient
      counterparts. The atheroprotective and HDL modulatory effects of G2A deficiency
      were dependent on the presence of ApoE, as deletion of G2A in ApoE(-/-) and ApoE(
      /-)LDLR(-/-) mice failed to raise HDL and did not suppress atherosclerosis. G2A
      deficiency in bone marrow-derived cells of LDLR(-/-) mice had no effect on
      atherosclerosis or HDL, whereas G2A deficiency in resident tissues was sufficient
      to raise HDL and suppress atherosclerosis. CONCLUSIONS: These data demonstrate
      that the chemotactic function of G2A in bone marrow-derived monocytes does not
      modulate atherosclerosis in LDLR(-/-) mice and suggest an ApoE-dependent function
      for G2A in the control of hepatic HDL metabolism that might contribute to its
      proatherogenic action.

PMID- 19164810
TI  - Vascular endothelial growth factor.
AB  - Vascular endothelial growth factor (VEGF, VEGF-A) is a major regulator of
      physiological and pathological angiogenesis. Several VEGF inhibitors have been
      approved by the FDA for the treatment of advanced cancer and neovascular age
      related macular degeneration. This brief review provides a historic account of
      the challenges associated with the discovery of VEGF and the early steps in
      elucidating the role of this molecule in the regulation of angiogenesis.

PMID- 19164811
TI  - Associations of pentraxin 3 with cardiovascular disease and all-cause death: the
      Cardiovascular Health Study.
AB  - OBJECTIVE: We examined associations of pentraxin 3 (PTX3), a vascular
      inflammation marker, with incident cardiovascular disease (CVD) and all-cause
      death. METHODS AND RESULTS: 1583 Cardiovascular Health Study participants free of
      prevalent CVD were included. Nonexclusive case groups were angina (n=476),
      myocardial infarction (MI; n=237), stroke (n=310), CVD death (n=282), and all
      cause death (n=772). 535 participants had no events. PTX3 levels were higher in
      those with subclinical CVD (1.90+/-1.89 ng/mL) than those without (1.71+/-1.88
      ng/mL; P=0.001). Using Cox regression adjusted for age, sex, and ethnicity, a
      standard deviation increase in PTX3 (1.89 ng/mL) was associated with CVD death
      (hazard ratio 1.11; 95% confidence interval 1.02 to 1.21) and all-cause death
      (1.08; 1.02 to 1.15). PTX3 was not associated with angina (1.09; 0.98 to 1.20),
      MI (0.96; 0.81 to 1.12), or stroke (1.06; 0.95 to 1.18). Adding C-reactive
      protein (CRP) or CVD risk factors to the models had no significant effects on
      associations. CONCLUSIONS: In these older adults, PTX3 was associated with CVD
      and all-cause death independent of CRP and CVD risk factors. PTX3 likely reflects
      different aspects of inflammation than CRP and may provide insight into vascular
      health in aging and chronic diseases of aging that lead to death.

PMID- 19164814
TI  - Creating and making the case: global advocacy for physical activity.

PMID- 19164813
TI  - Endothelial-mural cell signaling in vascular development and angiogenesis.
AB  - Mural cells are essential components of blood vessels and are necessary for
      normal development, homeostasis, and organ function. Alterations in mural cell
      density or the stable attachment of mural cells to the endothelium is associated
      with several human diseases such as diabetic retinopathy, venous malformation,
      and hereditary stroke. In addition mural cells are implicated in regulating tumor
      growth and have thus been suggested as potential antiangiogenic targets in tumor
      therapy. In recent years our knowledge of mural cell function and endothelial
      mural cell signaling has increased dramatically, and we now begin to understand
      the mechanistic basis of the key signaling pathways involved. This is mainly
      thanks to sophisticated in vivo experiments using a broad repertoire of genetic
      technologies. In this review, we summarize the five currently best understood
      signaling pathways implicated in mural cell biology. We discuss PDGFB/PDGFRbeta-
      dependent pericyte recruitment, as well as the role of angiopoietins and Tie
      receptors in vascular maturation. In addition, we highlight the effects of
      sphingosine-1-phosphate signaling on adherens junction assembly and vascular
      stability, as well as the role of TGF-beta-signaling in mural cell
      differentiation. We further reflect recent data suggesting an important function
      for Notch3 signaling in mural cell maturation.

PMID- 19164812
TI  - Suppressors of cytokine signaling modulate JAK/STAT-mediated cell responses
      during atherosclerosis.
AB  - OBJECTIVE: Suppressors of cytokine signaling (SOCS) proteins are intracellular
      regulators of receptor signal transduction, mainly Janus kinase/signal
      transducers and activators of transcription (JAK/STAT). We investigated the
      effects of SOCS modulation on the JAK/STAT-dependent responses in vascular cells,
      and their implication in atherosclerotic plaque development. METHODS AND RESULTS:
      Immunohistochemistry in human plaques revealed a high expression of SOCS1 and
      SOCS3 by vascular smooth muscle cells (VSMCs) and macrophages in the inflammatory
      region of the shoulders, when compared to the fibrous area. SOCS were also
      increased in aortic lesions from apoE(-/-) mice. In cultured VSMCs, endothelial
      cells, and monocytes, SOCS1 and SOCS3 were transiently induced by proinflammatory
      cytokines, proatherogenic lipoproteins, and immune molecules. Furthermore,
      overexpression of SOCS suppressed STAT activation and reduced inflammatory gene
      expression and cell growth, whereas SOCS knockdown increased these cell
      responses. In vivo, antisense oligodeoxynucleotides targeting SOCS3 exacerbated
      the atherosclerotic process in apoE(-/-) mice by increasing the size, leukocyte
      content, and chemokine expression in the lesions. CONCLUSIONS: SOCS expressed in
      atherosclerotic lesions are key regulators of vascular cell responses. Activation
      of this endogenous antiinflammatory pathway might be of interest in the treatment
      of atherosclerosis.

PMID- 19164815
TI  - Prevalence of insufficient physical activity and associated factors in Brazilian
      adolescents.
AB  - BACKGROUND: We aimed to describe levels of physical activity (PA) in adolescents
      living in southern Brazil and to explore associations between PA levels and
      demographic, socioeconomic, health-related, and parental variables. A further aim
      was to test the validity and reliability of the questionnaire used. METHODS: We
      conducted a population-based, cross-sectional study including 857 adolescents
      selected randomly. Insufficient PA was defined as <300 min/wk of MVPA. PA data
      collected by questionnaire were compared with pedometer counts and with a longer
      version of the questionnaire in a subsample of 92 adolescents. RESULTS:
      Reliability of the questionnaire was good, and its validity in comparison with a
      longer questionnaire was also satisfactory. In comparison with pedometer data,
      the questionnaire presented moderate agreement. The prevalence of insufficient PA
      in the whole sample was 69.8% (95% CI = 66.7-72.9). Boys were more active than
      girls. The prevalence of insufficient PA increased with age in girls but not in
      boys. Among boys, those from low socioeconomic levels were more likely to be
      sedentary. Among girls, paternal PA was directly associated with adolescent
      activity levels. CONCLUSIONS: Urgent strategies aimed at increasing levels of
      activity of adolescents are necessary in Brazil given the high prevalence of
      insufficient PA detected in this study. The variables associated with
      insufficient PA varied between boys and girls.

PMID- 19164816
TI  - Walking, cycling, and obesity rates in Europe, North America, and Australia.
AB  - PURPOSE: This study was designed to examine the relationship between active
      transportation (defined as the percentage of trips taken by walking, bicycling,
      and public transit) and obesity rates (BMI > or = 30 kg . m-2) in different
      countries. METHODS: National surveys of travel behavior and health indicators in
      Europe, North America, and Australia were used in this study; the surveys were
      conducted in 1994 to 2006. In some cases raw data were obtained from national or
      federal agencies and then analyzed, and in other cases summary data were obtained
      from published reports. RESULTS: Countries with the highest levels of active
      transportation generally had the lowest obesity rates. Europeans walked more than
      United States residents (382 versus 140 km per person per year) and bicycled more
      (188 versus 40 km per person per year) in 2000. DISCUSSION: Walking and bicycling
      are far more common in European countries than in the United States, Australia,
      and Canada. Active transportation is inversely related to obesity in these
      countries. Although the results do not prove causality, they suggest that active
      transportation could be one of the factors that explain international differences
      in obesity rates.

PMID- 19164817
TI  - Associations between aerobic and muscular fitness and cardiovascular disease
      risk: the northern Ireland young hearts study.
AB  - BACKGROUND: It is not clear what the relative contribution is of specific
      components of physical fitness (aerobic and muscular) to cardiovascular disease
      (CVD) risk. We investigated associations between aerobic fitness (endurance) and
      muscular fitness (power) and CVD risk factors. METHODS: Data were obtained from
      the Young Hearts project, a representative sample of 12- and 15-year-old boys and
      girls from Northern Ireland (N = 2016). Aerobic fitness was determined by the 20
      m shuttle run test, muscular fitness by the Sargent jump test. CVD risk factors
      included sum of skinfolds, systolic and diastolic blood pressure, serum total
      cholesterol (TC), HDL cholesterol, and TC:HDL ratio. Several linear regression
      analyses were conducted for 4 age and gender groups separately, with the risk
      factor as the outcome variable. RESULTS: Significant associations between aerobic
      fitness and a healthy CVD risk profile were found. These observed relationships
      were independent of power, whereas the (few) relationships between muscular
      fitness and the risk factors were partly explained by endurance. CONCLUSIONS:
      Tailored, preventive strategies during adolescence, incorporating endurance
      rather than power sports, could be encouraged to help prevent CVD. This is
      important because existing studies propose that healthiness during adulthood is
      founded on healthiness in adolescence.

PMID- 19164818
TI  - Effectiveness of face-to-face versus telephone support in increasing physical
      activity and mental health among university employees.
AB  - BACKGROUND: Follow-up support increases the effectiveness of physical activity
      interventions. This study evaluates the effectiveness of 2 support modes on
      physical activity and mental health. METHODS: University employees were randomly
      assigned to a coaching program with 4 face-to-face (N = 33) or telephone-based (N
      = 33) support contacts. Both programs included an initial face-to-face intake
      session and an informational brochure. Physical activity, trait anxiety, self
      efficacy, and social support were measured by self-report before and after the
      interventions that lasted 3 months. RESULTS: Both groups increased leisure-time
      physical activity, self-efficacy, and social support and decreased sitting time
      and trait anxiety. The only significant time by group interaction was found for
      active transportation. More specifically, participants in the face-to-face group
      reported a significant increase in their active transportation from pretest to
      posttest, whereas participants in the telephone group reported no significant
      change. CONCLUSIONS: Both face-to-face support and telephone support proved to be
      effective in increasing the physical activity level and mental health of
      university employees.

PMID- 19164819
TI  - Short-term adapted physical activity program improves bone quality in
      osteopenic/osteoporotic postmenopausal women.
AB  - BACKGROUND AND AIMS: It is known that people affected by osteopenia/osteoporosis
      can benefit from an adequate amount of physical activity, counteracting the
      progressive loss of bone and muscle mass caused by aging. Moreover, there is
      increasing evidence that exercise has positive effects on bone structure. The aim
      of our study was to evaluate the effects on bone tissue and muscular strength of
      a short-term exercise program in osteopenic/osteoporotic postmenopausal women.
      METHODS: Forty-nine osteopenic/osteoporotic postmenopausal women were divided
      into 2 groups: exercise and control. All subjects underwent 2 evaluations: before
      and after a training period. Bone quality was assessed by phalangeal quantitative
      osteosonography, and maximal strength of leg extensor muscles was also evaluated.
      The experimental group participated in a specific supervised 20-week physical
      activity program that included aerobic, balance, and strength training. RESULTS:
      After the training period, all bone parameters and lower-limb maximal strength
      were significantly improved in the exercise group (P < .05), whereas no
      significant changes were observed in the control group. CONCLUSIONS: Our study
      showed that a broad-based training protocol, lasting 20 weeks, can improve leg
      strength and bone quality parameters-main determinants of fall and fracture risk,
      respectively.

PMID- 19164821
TI  - Recruitment of obese black women into a physical activity and nutrition
      intervention trial.
AB  - BACKGROUND: Despite the increased health risks for obese Black women, relatively
      little research has explored physical activity and nutrition interventions for
      these women. This article describes the recruitment strategies used in a program
      designed specifically for obese Black women. METHODS: Recruitment of Black women
      age 30 to 65 years with body mass indices between 30 kg/m2and 50 kg/m2was
      completed using in-person recruitment and flyers within 2 miles of the
      intervention site along with mass e-mails within the sponsoring university
      system. Medical clearance from a physician was an eligibility requirement because
      of Institutional Review Board safety concerns. RESULTS: Of the 690 women who were
      screened, 213 (31%) were eligible and randomized. The most common reason for
      exclusion was failure to return a medical clearance form (n = 167, 39% of
      ineligible). Different rates of efficiency were noted across recruitment
      approaches. CONCLUSIONS: Black women were successfully recruited using in-person
      community recruitment, e-mail, and community flyers within close proximity to the
      intervention site. Careful consideration should be given to the advantages and
      disadvantages of various recruitment strategies that might not generalize across
      studies.

PMID- 19164820
TI  - Progressive improvement in glucose tolerance following lower-intensity resistance
      versus moderate-intensity aerobic training in older women.
AB  - BACKGROUND: Few studies have compared long-term moderate-intensity aerobic versus
      light-resistance training on serial improvements in glucose tolerance in older
      people. METHODS: Healthy, inactive older (74 +/- 5 [SD] years) women (N = 20)
      were randomized into either a high-volume, moderate-intensity aerobic (ATM, n =
      12) or a lower-intensity resistance training (RTL, n = 8) group. Both groups
      exercised under supervision 4 times per week for 45- to 60-min sessions over 9
      months. Measurements of plasma glucose, insulin, and free fatty acid (FFA)
      responses to an oral glucose tolerance test (OGTT) were performed at baseline and
      at 3, 6, and 9 months 48 hours after the last exercise session. RESULTS: We
      observed significant improvements in 2-hour glucose concentrations at 3, 6, and 9
      months among women in the RTL(152 +/- 42 vs 134 +/- 33 vs 134 +/- 24 vs 130 +/-
      27 mg x dL-1; P < .05), but not the ATM(151 +/- 25 vs 156 +/- 37 vs 152 +/- 40 vs
      155 +/- 39 mg x dL-1) group. These improvements were accompanied by an 18% (P <
      .07) decrease in basal FFA concentrations in the RTLgroup, whereas basal and 30
      min FFA concentrations increased (P < .05) after training in the ATMgroup.
      CONCLUSIONS: These findings suggest that the net physiological benefits of
      exercise might have been blunted in the ATMgroup, owing to higher circulating
      levels of FFA, which might have temporarily interfered with insulin action.

PMID- 19164822
TI  - Using accelerometer feedback to identify walking destinations, activity
      overestimates, and stealth exercise in obese and nonobese individuals.
AB  - BACKGROUND: Accelerometer output feedback might enable assessment of recall
      biases for moderate bouts by obese and nonobese individuals; accelerometry might
      also help residents recall destinations for moderate-intensity walking bouts.
      METHODS: Adult residents' 1-week accelerometer-measured physical activity and
      obesity status were measured before and after a new rail stop opened (n = 51 Time
      1; n = 47 Time 2). Participants recalled the week's walking bouts, described them
      as brisk (moderate) or not, and reported a rail stop destination or not. RESULTS:
      At the end of the week, we provided accelerometry output to residents as a
      prompt. Recall of activity intensity was accurate for about 60% of bouts.
      Nonobese participants had more moderate bouts and more "stealth exercise" -
      moderate bouts recalled as not brisk--than did obese individuals. Obese
      participants had more overestimates--recalling light bouts as brisk walks--than
      did nonobese individuals. Compared with unprompted recall, accelerometry-prompted
      recalls allowed residents to describe where significantly more moderate bouts of
      activity occurred. CONCLUSION: Coupling accelerometry feedback with self-report
      improves research by measuring the duration, intensity, and destination of
      walking bouts. Recall errors and different patterns of errors by obese and
      nonobese individuals underscore the importance of validation by accelerometry.

PMID- 19164823
TI  - Physical activity patterns and preferences among Latinos in different types of
      public parks.
AB  - BACKGROUND: Centers for Disease Control (CDC) data suggest that Latinos are less
      likely to be physically active and more likely to be overweight and suffer from
      resulting complications than are Whites and that within the Latino population,
      Latina women are especially at risk. Therefore, promoting physical activity among
      Latinos, and understanding gender participation patterns within that population,
      is particularly important. One strategy for encouraging physical activity is to
      promote active uses of public parks. METHODS: A national, multiyear, multisite
      study funded by the USDA Forest Service sought to understand use of public parks
      by Latinos and Latinas in Los Angeles, Minneapolis, and Chicago. RESULTS: More
      than 50% of our sample visited parks to engage in physical activity, and in part,
      activity choice was related to gender. Furthermore, nearly half of all
      respondents walked to city park sites, whereas few or none walked to state or
      regional park sites. CONCLUSIONS: Our data suggest that Latinos are using some
      parks repeatedly and, in the case of city parks, are using them for physical as
      well as social activity. Therefore, we suggest specific ways that parks could be
      managed to encourage more physical activity while taking into account gender
      variations.

PMID- 19164824
TI  - Conducting environmental assessments for physical activity: determining traffic
      volume in walkability audits in two West Virginia communities.
AB  - BACKGROUND: In this article, we examine the possibility of reducing time to
      conduct traffic volume audits through (1) reducing time for manual traffic
      counting and (2) using Department of Transportation (DOT) information. METHODS:
      In audits of 824 road segments in 2 West Virginia (WV) communities, manual
      traffic counts were recorded for 1, 2, and 5 min in duration. Annual Average
      Daily Traffic (AADT) was calculated from counts. Available AADT from DOT was also
      collected. Percent agreement and a weighted kappa were calculated between 5-min
      count and 1- and 2-min count AADT categories and between 5-min count and DOT AADT
      categories. RESULTS: One- and 2-min counts produced identical AADT categories as
      5-min counts in 93.4% and 95.0% of segments, respectively. Weighted kappa was
      0.79 (95% CI = 0.74-0.85) and 0.85 (95% CI = 0.80-0.89), respectively. Forty-two
      segments (5.1%) had DOT data. CONCLUSIONS: DOT AADT was available for a small
      percentage of road segments assessed. The high agreement between AADT categories
      produced by 1- and 2-min counts and 5-min counts makes it reasonable to consider
      using 1- or 2-min manual traffic counts if time or staffing constraints make it
      necessary. Possible generalizability of this methodology to other communities,
      particularly larger urban and suburban areas, will require further research.

PMID- 19164825
TI  - Physical activity and prostate cancer mortality in Puerto Rican men.
AB  - Studies on the association between physical activity and fatal prostate cancer
      have produced inconclusive results. The Puerto Rico Heart Health Program was a
      cohort study of a randomly selected sample of 9824 men age 35 to 79 years at
      baseline who were followed for mortality until 2002. Multiple examinations
      collected information on lifestyle, diet, body composition, exercise, urban-rural
      residence, and smoking habits. Physical activity status was measured using the
      Framingham Physical Activity Index, an assessment of occupational, leisure-time,
      and other physical activities measured as usual activity over the course of a 24
      hour day. Physical activity was stratified into quartiles. Multivariate logistic
      regression analysis was used to assess the association of physical activity with
      prostate cancer mortality. Other covariates included age, education, urban-rural
      residence, smoking, and body mass index. Compared with the lowest level of
      physical activity (Q1), the risk of prostate cancer mortality was OR = 0.99 (95%
      CI = 0.64-1.55) for Q2, OR = 1.34 (95% CI = 0.88-2.05) for Q3, and OR = 1.19 (95%
      CI = 0.75-1.90) for Q4. Further analyses by age group, overweight status, or
      vigorous physical activity also did not show a significant association between
      physical activity and prostate cancer mortality. Physical activity did not
      predict prostate cancer mortality in this group of Puerto Rican men.

PMID- 19164826
TI  - Systematic review of active commuting to school and childrens physical activity
      and weight.
AB  - BACKGROUND: The recent decline in children's active commuting (walking or biking)
      to school has become an important public health issue. Recent programs have
      promoted the positive effects of active commuting on physical activity (PA) and
      overweight. However, the evidence supporting such interventions among
      schoolchildren has not been previously evaluated. METHODS: This article presents
      the results of a systematic review of the association between active commuting to
      school and outcomes of PA, weight, and obesity in children. RESULTS: We found 32
      studies that assessed the association between active commuting to school and PA
      or weight in children. Most studies assessing PA outcomes found a positive
      association between active commuting and overall PA levels. However, almost all
      studies were cross-sectional in design and did not indicate whether active
      commuting leads to increased PA or whether active children are simply more likely
      to walk. Only 3 of 18 studies examining weight found consistent results,
      suggesting that there might be no association between active commuting and
      reduced weight or body mass index. CONCLUSION: Although there are consistent
      findings from cross-sectional studies associating active commuting with increased
      total PA, interventional studies are needed to help determine causation.

PMID- 19164827
TI  - Nutritional practices of male cyclists before and during an ultraendurance event.
AB  - The aim of the study was to investigate the pre- and during-race nutritional
      intake of cyclists competing in a 210-km 1-day ultraendurance cycle race. Forty
      five endurance-trained male cyclists participated in this dietary survey and
      completed a 3-day dietary record. Mean reported carbohydrate (CHO) intake over
      the 3 days before the race (5.6 +/- 1.7 g/kg) was below the recommended
      guidelines of 7-10 g/kg. Although 57% of participants indicated that they CHO
      loaded 1-3 days before the race, only 23% of these participants achieved CHO
      intakes of > or =7 g/kg over the 3-day period before the race, demonstrating a
      discrepancy between perceived and actual intakes of CHO. Most participants
      indicated the use of CHO supplements before (84%) and during (98%) the race and
      achieved a CHO intake of 63 +/- 23 g/hr during the race. Although most cyclists
      failed to meet recommended prerace CHO intakes, most achieved the recommended CHO
      intakes during the race.

PMID- 19164828
TI  - Carbohydrate, protein, and fat metabolism during exercise after oral carnitine
      supplementation in humans.
AB  - Twenty nonvegetarian active males were pair-matched and randomly assigned to
      receive 2 g of L-carnitine L-tartrate (LC) or placebo per day for 2 wk.
      Participants exercised for 90 min at 70% VO2max after 2 days of a prescribed diet
      (M +/- SD: 13.6 +/- 1.6 MJ, 57% carbohydrate, 15% protein, 26% fat, 2% alcohol)
      before and after supplementation. Results indicated no change in carbohydrate
      oxidation, nitrogen excretion, branched-chain amino acid oxidation, or plasma
      urea during exercise between the beginning and end of supplementation in either
      group. After 2 wk of LC supplementation the plasma ammonia response to exercise
      tended to be suppressed (0 vs. 2 wk at 60 min exercise, 97 +/- 26 vs. 80 +/- 9,
      and 90 min exercise, 116 +/- 47 vs. 87 +/- 25 micromol/L), with no change in the
      placebo group. The data indicate that 2 wk of LC supplementation does not affect
      fat, carbohydrate, and protein contribution to metabolism during prolonged
      moderate-intensity cycling exercise. The tendency toward suppressed ammonia
      accumulation, however, indicates that oral LC supplementation might have the
      potential to reduce the metabolic stress of exercise or alter ammonia production
      or removal, which warrants further investigation.

PMID- 19164829
TI  - The influence of carbohydrate mouth rinse on self-selected speeds during a 30-min
      treadmill run.
AB  - The purpose of this study was to examine the influences of a carbohydrate (CHO)
      mouth rinse on self-selected running speeds during a 30-min treadmill run. Ten
      endurance-trained men performed 2 trials, each involving a 10-min warm-up at 60%
      VO2max followed by a 30-min run. The run was performed on an automated treadmill
      that allowed the spontaneous selection of speeds without manual input.
      Participants were asked to run at speeds that equated to a rating of perceived
      exertion of 15, mouth rinsing with either a 6% CHO or taste-matched placebo (PLA)
      solution. In addition to recording self-selected speeds and total distance
      covered the authors assessed the runners' subjective feelings. The total distance
      covered was greater during the CHO than during the PLA trial (p < .05). Faster
      speeds selected during the first 5 min of exercise corresponded with enhanced
      feelings of pleasure when mouth rinsing with the CHO solution. Mouth rinsing with
      a CHO solution increased total distance covered during a self-selected 30-min run
      in comparison with mouth rinsing with a color- and taste-matched placebo.

PMID- 19164830
TI  - Oral quercetin supplementation and blood oxidative capacity in response to
      ultramarathon competition.
AB  - Previous research indicates that ultramarathon exercise can result in blood
      oxidative stress. The purpose of this investigation was to examine the efficacy
      of oral supplementation with quercetin, a naturally occurring compound with known
      antioxidant properties, as a potential countermeasure against blood oxidative
      stress during an ultramarathon competition. In double-blind fashion, 63
      participants received either oral quercetin (250 mg, 4x/day; 1,000 mg/day total)
      or quercetin-free supplements 3 weeks before and during the 160-km Western States
      Endurance Run. Blood drawn before and immediately after (quercetin finishers n =
      18, quercetin-free finishers n = 21) the event was analyzed for changes in blood
      redox status and oxidative damage. Results show that quercetin supplementation
      did not affect race performance. In response to the ultramarathon challenge,
      aqueous-phase antioxidant capacity (ferric-reducing ability of plasma) was
      similarly elevated in athletes in both quercetin and quercetin-free treatments
      and likely reflects significant increases in plasma urate levels. Alternatively,
      trolox-equivalent antioxidant capacity was not altered by exercise or quercetin.
      Accordingly, neither F2-isoprostances nor protein carbonyls were influenced by
      either exercise or quercetin supplementation. In the absence of postrace blood
      oxidative damage, these findings suggest that oral quercetin supplementation does
      not alter blood plasma lipid or aqueous-phase antioxidant capacity or oxidative
      damage during an ultramarathon challenge.

PMID- 19164831
TI  - Ramadan fastings effect on plasma leptin, adiponectin concentrations, and body
      composition in trained young men.
AB  - PURPOSE: To evaluate the effect of Ramadan fasting on parameters of insulin
      resistance in trained athletes at rest and after aerobic exercise. METHODS: Nine
      male rugby players (age 19 +/- 2 yr, height 1.78 +/- 0.74 m) were tested 3 times:
      1 week before observance of Ramadan (C), at the end of the first week (R1), and
      during the fourth week (R2). They performed a progressive cycle-ergometer test at
      each visit. Data collected at rest and at the end of aerobic exercise included
      simple anthropometry (body mass, body-mass index, body fat, fat-free mass),
      biochemical parameters (serum glucose, cholesterol, HDL cholesterol,
      triglycerides, creatinine, and serum proteins), and selected hormone
      concentrations (plasma insulin, leptin, and adiponectin). RESULTS: Ramadan
      fasting was associated with a reduction of body mass and body fat (R2 vs. C, p <
      .01) without significant change in leptin or adiponectin levels. CONCLUSION:
      Lipolysis might have occurred because of increased plasma triglycerides and HDL
      cholesterol concentrations.

PMID- 19164832
TI  - Body image and body composition: comparisons of young male elite soccer players
      and controls.
AB  - The purpose of this study was to evaluate body composition and body image
      (perception and satisfaction) in a group of young elite soccer players and to
      compare the data with those of a control group (age and BMI matched).
      Participants were 56 volunteer males whose mean age and BMI were 19.6 (SD 1.3)
      years and 23.3 (SD 1.1) kg/m2, respectively. Results showed that soccer players
      have a higher lean mass and lower fat mass than controls. Moreover, body
      perception (difference between current and actual image) was more accurate in
      controls than in soccer players, and the results suggest a tendency for soccer
      players to aspire to have more muscle mass and body fat. Soccer players perceived
      an ideal image with significantly higher body-fat percentage than their current
      and actual images. There were no body-dissatisfaction differences between groups,
      however. Although the results are necessarily limited by the small sample size,
      the findings should be of interest to coaches of young elite soccer teams.

PMID- 19164833
TI  - Caffeines enhancement of maximal voluntary strength and activation in uninjured
      but not injured muscle.
AB  - The study's objective was to determine whether orally ingested caffeine could
      help overcome excitation-contraction-coupling failure, which has been suggested
      to explain part of the strength loss associated with eccentric-contraction
      induced muscle injury. A sample of 13 college students (4 men and 9 women) was
      used in a double-blind, repeated-measures experimental design. Each participant
      performed 2 experimental trials, 1 with each leg, with each trial lasting 4
      consecutive days. On a given day, each participant was randomly assigned to
      ingest a capsule containing 6 mg/kg of either caffeine or flour (placebo). On the
      day of and the first 2 days after a bout of 50 injurious eccentric contractions
      done by the knee extensors, the interpolated-twitch technique was used to assess
      electrically evoked strength, maximal voluntary isometric contraction (MVIC)
      strength, and percent muscle activation during MVIC both before and after capsule
      ingestion. These variables were also measured before and after capsule ingestion
      the day before the eccentric-contraction bout--when the muscle was uninjured. In
      injured muscle, caffeine had no effect on any variable. In uninjured muscle,
      caffeine also had no effect on electrically evoked strength but increased MVIC
      strength by 10.4% compared with placebo (p = .00002), and this was attributed to
      an increase in muscle activation (6.2%; p = .01). In conclusion, the data provide
      no evidence that caffeine ingestion can help overcome excitation-contraction
      coupling failure, if it exists, in injured human muscle. The data do indicate
      that caffeine ingestion can increase MVIC strength and activation in uninjured
      muscle but not in injured muscle.

PMID- 19164834
TI  - Acute effects of dietary ginger on quadriceps muscle pain during moderate
      intensity cycling exercise.
AB  - Ginger has known hypoalgesic and anti-inflammatory properties. The effects of an
      oral dose of ginger on quadriceps muscle pain, rating of perceived exertion
      (RPE), and recovery of oxygen consumption were examined during and after moderate
      intensity cycling exercise. Twenty-five college-age participants ingested a 2-g
      dose of ginger or placebo in a double-blind, crossover design and 30 min later
      completed 30 min of cycling at 60% of VO2peak. Quadriceps muscle pain, RPE, work
      rate, heart rate (HR), and oxygen uptake (VO2) were recorded every 5 min during
      exercise, and HR and VO2 were recorded for 20 min after exercise. Compared with
      placebo, ginger had no clinically meaningful or statistically significant effect
      on perceptions of muscle pain, RPE, work rate, HR, or VO2 during exercise.
      Recovery of VO2 and HR after the 30-min exercise bout followed a similar time
      course in the ginger and placebo conditions. The results were consistent with
      related findings showing that ingesting a large dose of aspirin does not acutely
      alter quadriceps muscle pain during cycling, and this suggests that
      prostaglandins do not play a large role in this type of exercise-induced skeletal
      muscle pain. Ginger consumption has also been shown to improve VO2 recovery in an
      equine exercise model, but these results show that this is not the case in
      humans.

PMID- 19164835
TI  - The development of anticipation: a cross-sectional examination of the practice
      experiences contributing to skill in cricket batting.
AB  - The link between the anticipation skills of cricket batsmen and their practice
      histories was examined. Skilled and lesser skilled batsmen of U15, U20, and adult
      age completed a temporal occlusion task, in which they were required to use
      prerelease kinematic information to predict the type and length of delivery being
      bowled, and a structured interview, in which their accumulated hours of
      experience in organized and unorganized sporting activities were estimated.
      Skilled adult and U20 players showed an ability to use prerelease kinematic
      information to anticipate ball type that was not evident among any other group,
      and skilled players of all ages were distinguishable in terms of their
      accumulated hours of cricket-specific experience. Hours of cricket-specific
      practice, however, explained only a modest percentage of the variance in
      anticipatory skill. Discussion focuses upon future refinements to the measurement
      of anticipation and practice history plus the role that variables other than the
      quantum of cricket experience may play in developing anticipation.

PMID- 19164836
TI  - The contribution of structured activity and deliberate play to the development of
      expert perceptual and decision-making skill.
AB  - The developmental histories of 32 players in the Australian Football League
      (AFL), independently classified as either expert or less skilled in their
      perceptual and decision-making skills, were collected through a structured
      interview process and their year-on-year involvement in structured and deliberate
      play activities retrospectively determined. Despite being drawn from the same
      elite level of competition, the expert decision-makers differed from the less
      skilled in having accrued, during their developing years, more hours of
      experience in structured activities of all types, in structured activities in
      invasion-type sports, in invasion-type deliberate play, and in invasion
      activities from sports other than Australian football. Accumulated hours invested
      in invasion-type activities differentiated between the groups, suggesting that it
      is the amount of invasion-type activity that is experienced and not necessarily
      intent (skill development or fun) or specificity that facilitates the development
      of perceptual and decision-making expertise in this team sport.

PMID- 19164837
TI  - The effect of participation in Gaelic football on the development of Irish
      professional soccer players.
AB  - The developmental model of sport participation (DMSP) was proposed by Cote
      (1999). First, we examined whether the participation profiles of two groups of
      professional soccer players in Ireland who either had or had not played Gaelic
      football to an elite level in adolescence provided support for this model. Both
      groups commenced participation in soccer around 6 years of age and on average
      participated in two other sports between 6 and 18 years of age, excluding soccer
      and Gaelic football. A reduction in the number of other sports and an increase in
      hours devoted to the primary sport were observed between 6 and 18 years of age,
      as per the predictions of the DMSP. Second, we examined whether players who
      demonstrated early diversification required fewer soccer-specific hours to
      achieve expert performance in that sport compared with players who demonstrated
      less diversification or did not participate in Gaelic football. No significant
      relationships or differences were reported, which did not provide support for the
      DMSP, possibly due to the low sample size employed in this study.

PMID- 19164838
TI  - Especial skills: specificity embedded within generality.
AB  - Recent evidence suggests that massive amounts of practice of the basketball free
      throw (a "set shot") results in the development of a specific memory
      representation that is unique to this one shot distance and angle, and that is
      distinct from set shots taken at locations other than the free throw line. We
      termed this unique capability an especial skill. In this article, we review the
      evidence and provide new data regarding the existence of especial skills. These
      findings are discussed in terms of their implications for motor control theory
      and in terms of the broader context of specificity versus generality in the
      learning of motor skills.

PMID- 19164839
TI  - Explaining performance in elite middle-aged runners: contributions from age and
      from ongoing and past training factors.
AB  - Researchers have contended that patterns of age-related decline are not
      necessarily due to age, but rather to disuse, or declining practice (Bortz, 1982;
      Ericsson, 2000; Maharam, Bauman, Kalman, Skolnik, & Perle, 1999). A regression
      approach was used to examine age and training variables as predictors of 10-km
      running performance between 40 and 59 years of age. A sample of 30 Masters
      runners (M age=50.1 years, M 10-km time=39:19) reported data for ongoing
      training, cumulative running in the past 5 years, and cumulative running earlier
      in a career. In Analysis 1, ongoing training variables explained more variance in
      performance than age alone, and reduced the unique variance attributable to age
      in a combined model. In Analysis 2, findings were replicated using past
      cumulative running variables and age; running in the past 5 years explained more
      unique variance than age alone. Discussion focuses on how findings relate to the
      selective maintenance account (Krampe & Ericsson, 1996), how various aspects of
      training help to preserve performance in aging populations, and recommendations
      for future research.

PMID- 19164840
TI  - How baseball players prepare to bat: tactical knowledge as a mediator of expert
      performance in baseball.
AB  - Our understanding of the role of tactical knowledge in baseball batting
      preparation is scarce, thereby limiting training guidelines. We examined the
      verbal reports of baseball players and nonplayers when told to view different
      edited video sequences of a half-inning of baseball competition under different
      task conditions: to prepare to bat (problem solve); recall as much information as
      possible (intentional recall); or prepare to bat, with an unexpected recall
      (incidental recall). Separate mixed-model ANOVAs (Expertise x Instruction
      conditions) on verbal report measures indicated that nonplayers used general
      strategies for recalling baseball events and lacked the tactical skills to use
      such information for their upcoming times at bat. In contrast, players used
      baseball-specific strategies to encode and retrieve pertinent game events from
      long-term memory (LTM) to develop tactics for their upcoming times at bat and to
      recall as much information as possible. Recommendations for training tactical
      skills are presented as some players exhibited deficiencies in the LTM structures
      that mediate batting decisions.

PMID- 19164841
TI  - Introduction: reproductive mental health--Motherisk update 2008.
AB  - On May 7th 2008, our annual Motherisk Update was devoted to reproductive mental
      health, which is a part of life for many women of childbearing age. Presentations
      were delivered by experts int he fields of psychiatry, maternal/fetal
      pharmacology and obstetrics. Our goal was to improve patient care for a
      population that is particularly vulnerable to misinformation and the stigma that
      surrounds mental illness. The topics presented, included the prevalence of
      depression and other psychiatric illnesses during pregnancy and postpartum, the
      adverse consequences of untreated psychiatric illnesses in pregnancy and
      postpartum and the treatment of substance abuse which is often a comorbidity in
      these women. We also provided information on the risk/safety of drugs used for
      the treatment of these conditions in pregnancy and breastfeeding,including
      concerns regarding neonatal withdrawal in infants who were exposed to
      antidepressants during pregnancy.

PMID- 19164842
TI  - Mood disorders in women: focus on reproductive psychiatry in the 21st century-
      Motherisk update 2008.
AB  - The burden of mental illness in general, and depression in particular, has long
      been underestimated. One in 6 persons in the United States will, at some point,
      suffer from major depression. Depression is second only to heart disease as a
      leading cause of medical disability in the U.S. Women are vulnerable to mood
      instability at times of life-cycle related hormonal challenge (e.g., including
      the premenstruum, pregnancy, post-miscarriage, postpartum and perimenopause).
      Neurobiological, genetic, and psychosocial substrates underlie the increased
      vulnerability for depression in women. The significant negative impact of
      maternal depression on maternal and child health and psychological well-being and
      other possible consequences of chronic depression will be reviewed. The enormous
      burden of female depression on women, their children and their families has been
      well-documented over the past two decades. What remains is the need for serious,
      rigorously conducted research into effective and safe treatments for depression
      in women, particularly at times of reproductive transition.

PMID- 19164843
TI  - Depression during pregnancy: rates, risks and consequences--Motherisk Update
      2008.
AB  - Affective illness is common in women, and the puerperium is a time of particular
      vulnerability. Gender differences in the expression of affective disorders have
      been attributed to the impact of hormonal influence, socialization, and genetics.
      Dramatic fluctuations in gonadal hormones that occur following childbirth,
      influences the increased incidence of mood disorders during this time. Numerous
      tools including the Edinburgh Postpartum Depression Scale can be used to screen
      for depression during pregnancy and postpartum. While screening tools may assist
      with appropriately identifying women who should be further assessed, their use
      alone does not significantly increase treatment seeking in women, even when their
      providers are notified about risk. Many studies demonstrate that only a small
      number (18%) of women who meet criteria for major depressive disorder seek
      treatment during pregnancy and postpartum. Additionally, common symptoms of
      depression (sleep, energy and appetite change) may be misinterpreted as normative
      experiences of pregnancy.Treatment engagement is important as untreated
      depression during pregnancy may have unfavorable outcomes for both women and
      children. Complications of pregnancy associated with depression include:
      inadequate weight gain,under utilization of prenatal care, increased substance
      use, and premature birth. Human studies demonstrate that perceived life-event
      stress, as well as depression and anxiety predicted lower birth weight, decreased
      Apgar scores, and smaller head circumference, and small for gestational age
      babies. Postpartum depression (PPD) is a common clinical disorder occurring in
      15% of deliveries,making it one of the most frequent conditions to complicate
      pregnancy. Risk factors include past personal or family history of depression,
      sing marital status, poor health functioning, lower SES, and alcohol use. Women
      who have a prior history of postpartum depression, particularly with features of
      bipolarity or psychosis may be at particularly high risk.

PMID- 19164844
TI  - Understanding and treating women with schizophrenia during pregnancy and
      postpartum--Motherisk Update 2008.
AB  - This article provides a synopsis of clinically relevant data pertaining to
      sexuality, pregnancy, the postpartum period, parenting and family planning in
      women with schizophrenia. Based on this information, we propose recommendations
      for the non-pharmacological management of these patients. Along with the
      deinstitutionalization of people with severe and persistent mental illness, there
      has been a concurrent increase in relative fertility in women with
      schizophrenia.Understanding the nature and experience of sexuality in women with
      schizophrenia helps elucidate the context in which pregnancies
      occur.Schizophrenia does not diminish sexual desire or activity. However, the
      quality and relational context of sexuality may be markedly different.Pregnancy
      appears to worsen mental health in a subset of women with schizophrenia.
      Psychotic denial of pregnancy is a symptom that poses especially high risks for
      poor outcomes if not addressed. Psychoeducation can reduce the risks of pregnancy
      complications for women with schizophrenia. Short-term, focused psychotherapy can
      be useful for some pregnant women with schizophrenia. Some modifications need to
      be made in the inpatient treatment of pregnant patients with schizophrenia. In
      the postpartum period, women can be especially susceptible for acute exacerbation
      of their schizophrenia. With regards to parenting, many women will provide
      intermittent parenting for their children while others will lose custody of their
      children. Those mothers with schizophrenia who do raise their children may face
      unique challenges in parenting.Both positive and negative symptoms can interfere
      with the demands of being a parent.A comprehensive parenting assessment of the
      patient can provide guidance for the implementation of supportive services.
      Proactive family planning could reduce the high rate of unwanted pregnancies, as
      women with schizophrenia tend to have more limited knowledge of their
      contraceptive options.

PMID- 19164845
TI  - Management of bipolar II disorder during pregnancy and the postpartum period-
      Motherisk Update 2008.
AB  - The spectrum of bipolar disorder (BPD) includes BP I, BP II, and BP not otherwise
      specified(NOS). The latter two conditions are thought to have a combined lifetime
      prevalence of 3.5%compared to a prevalence rate of 1.0% for BP I.Despite the
      combined high prevalence of BP II and BP NOS, surprisingly little is known about
      the course and treatment of these disorders during pregnancy and the postpartum
      period. Brief hypomanic symptoms occur in the early puerperium in as many as 15%
      of women, and there is preliminary evidence that postpartum depression in some
      patients may be related to BP II or BP NOS. Yet there is paucity of data on the
      acute, and maintenance treatment of major depressive episodes during pregnancy in
      women with BP II and BP NOS. And there are no psychopharmacological studies on
      the acute or maintenance treatment of bipolar postpartum depression to guide
      clinical decision making. Also, there is a lack of screening instruments designed
      specifically for use before or after delivery in women with suspected bipolar
      disorder. This paper reviews the current literature on the diagnosis, and
      treatment of BP II and BP NOS during pregnancy and in the postpartum period and
      makes recommendations for the detection and treatment of these disorders.

PMID- 19164846
TI  - Psychotropic drugs in lactation--Motherisk Update 2008.
AB  - Breast feeding is accompanied by numerous clinical and psychosocial advantages
      for both the mother and her child. Since most drugs will pass into human milk in
      some amount, the lactating mother who requires pharmacotherapy adds complexity to
      the risk-benefit assessment for clinicians making treatment decisions. In the
      case of psychotropic medications this issue is particularly worrisome since women
      who are not well controlled will have impaired bonding with their child.
      Moreover, these women may not necessarily recognize adverse events or abnormal
      outcomes in her infants. In an ideal situation, the patient would receive
      pharmacotherapy to assist in disease management, while at the same time
      successfully breastfeed her child. This goal of this presentation is to discuss
      the disposition of drugs in lactating patients and to outline the available
      literature concerning the use of psychotropic drugs in lactating women. Part of
      the continuum of treating women with psychiatric disease in pregnancy concerns
      the treatment of women after delivery, and for many, this will include drug
      treatment during lactation. The goal of today's discussion is to describe the
      issues and outline what is currently known about the use of psychotropic drugs in
      breastfeeding women.

PMID- 19164847
TI  - Risks/safety of psychotropic medication use during pregnancy--Motherisk Update
      2008.
AB  - Psychiatric disorders are relatively common among women of childbearing age, who
      may be prescribed psychotropic drugs. There remains a high level of anxiety
      regarding their safety among patients and healthcare providers alike, most likely
      because of the conflicting studies that have been published in the literature and
      warnings from government organizations. Consequently, treating a psychiatric
      disorder during pregnancy with pharmacotherapy, is a complex decision making
      process, which has to be made between the pregnant woman and her healthcare
      provider. The objective of this brief review is to discuss the current models for
      studying the use of drugs in pregnancy and to provide current information on the
      safety/risk of psychotropic drugs used in pregnancy. The body of evidence in the
      literature to date suggests that psychotropic drugs as a group are relatively
      safe to take during pregnancy and women and their health care providers should
      not be unduly concerned if a woman requires treatment. Optimal control of the
      psychiatric disorder should be maintained during pregnancy, the post partum
      period and thereafter.All pregnancies where a mother has a serious psychiatric
      disorder should be considered high risk and the mother and fetus must be
      carefully monitored.

PMID- 19164848
TI  - Adverse effects in neonates exposed to SSRIs and SNRI in late gestation-
      Motherisk Update 2008.
AB  - Neonates exposed at term to selective serotonine (SSRI) or serotonine
      norepinephrine reuptake inhibitors (SNRI) medications may encounter symptoms such
      as irritability, rigidity, tremor and respiratory distress. Most available data
      suggest that these self limited symptoms are due to discontinuation of the drug,
      although there are documented cases of symptoms associated with high serum
      concentrations in the neonate that subsided when levels fall. Preliminary
      evidence suggests that the very early respiratory symptoms may not be part of
      discontinuation but rather part of a reversible form of persistent pulmonary
      hypertension of the newborn (PPHN).

PMID- 19164849
TI  - Glial cell line-derived neurotrophic factor added to a sciatic nerve fragment
      grafted in a spinal cord gap ameliorates motor impairments in rats and increases
      local axonal growth.
AB  - PURPOSE: The aversive nature of regenerative milieu is the main problem related
      to the failure of neuronal restoration in the injured spinal cord which however
      might be addressed with an adequate repair intervention. We evaluated whether
      glial cell line-derived neurotrophic factor (GDNF) may increase the ability of
      sciatic nerve graft, placed in a gap promoted by complete transections of the
      spinal cord, to enhance motor recovery and local fiber growth. METHODS: Rats
      received a 4 mm-long gap at low thoracic level and were repaired with a fragment
      of the sciatic nerve. GDNF was added (NERVE+/-GDNF) or not to the grafts (NERVE-
      GDNF). Motor behavior score (BBB) and sensorimotor tests-linked to the combined
      behavior score (CBS), which indicate the degree of the motor improvement and the
      percentage of functional deficit, respectively, and also the spontaneous motor
      behavior in an open field by means of an infrared motion sensor activity monitor
      were analyzed. At the end of the third month post surgery, the tissue composed by
      the graft and the adjacent regions of the spinal cord was removed and submitted
      to the immunohistochemistry of the neurofilament-200 (NF-200), growth associated
      protein-43 (GAP-43), microtubule associated protein-2 (MAP-2), 5
      hidroxytryptamine (serotonin, 5-HT) and calcitonin gene related peptide (CGRP).
      The immunoreactive fibers were quantified at the epicenter of the graft by means
      of stereological procedures. RESULTS: Higher BBB and lower CBS levels (p < 0.001)
      were found in NERVE+/-GDNF rats. GDNF added to the graft increased the levels of
      individual sensorimotor tests mainly at the third month. Analysis of the
      spontaneous motor behavior showed decreases in the time and number of small
      movement events by the third month without changes in time and number of large
      movement events in the NERVE$+$GDNF rats. Immunoreactive fibers were encountered
      inside the grafts and higher amounts of NF-200, GAP-43 and MAP-2 fibers were
      found in the epicenter of the graft when GDNF was added. A small amount of
      descending 5-HT fibers was seen reentering in the adjacent caudal levels of the
      spinal cords which were grafted in the presence of GDNF, event that has not
      occurred without the neurotrophic factor. GDNF in the graft also led to a large
      amount of MAP-2 perikarya and fibers in the caudal levels of the cord gray
      matter, as determined by the microdensitometric image analysis. CONCLUSIONS: GDNF
      added to the nerve graft favored the motor recovery, local neuronal fiber growth
      and neuroplasticity in the adjacent spinal cord.

PMID- 19164850
TI  - Upper extremity improvements in chronic stroke: coupled bilateral load training.
AB  - BACKGROUND: The current treatment intervention study determined the effect of
      coupled bilateral training (i.e., bilateral movements and EMG-triggered
      neuromuscular stimulation) and resistive load (mass) on upper extremity motor
      recovery in chronic stroke. METHODS: Thirty chronic stroke subjects were randomly
      assigned to one of three behavioral treatment groups and completed 6 hours of
      rehabilitation in 4 days: (1) coupled bilateral training with a load on the
      unimpaired hand, (2) coupled bilateral training with no load on the unimpaired
      hand, and (3) control (no stimulation assistance or load). RESULTS: Separate
      mixed design ANOVAs revealed improved motor capabilities by the coupled bilateral
      groups. From the pretest to the posttest, both the coupled bilateral no load and
      load groups moved a higher number of blocks and demonstrated more regularity in
      the sustained contraction task. Faster motor reaction times across test sessions
      for the coupled bilateral load group provided additional evidence for improved
      motor capabilities. CONCLUSIONS: Together these behavioral findings lend support
      to the contribution of coupled bilateral training with a load on the unimpaired
      arm to improved motor capabilities on the impaired arm. This evidence supports a
      neural explanation in that simultaneously moving both limbs during stroke
      rehabilitation training appears to activate balanced interhemispheric
      interactions while an extra load on the unimpaired limb provides stability to the
      system.

PMID- 19164851
TI  - Different postischemic protein expression of the GABA(A) receptor alpha2 subunit
      and the plasticity-associated protein MAP1B after treatment with BDNF versus G
      CSF in the rat brain.
AB  - PURPOSE: Recent data indicate that both brain-derived neurotrophic factor (BDNF)
      and granulocyte-colony stimulating factor (G-CSF) exert substantial
      neuroregenerative effects and improve functional outcome after ischemic stroke.
      In the present study, we checked for potential differences in the postischemic
      modulation of various excitatory and inhibitory neurotransmitter receptors as
      well as various marker molecules for structural plasticity by BDNF versus G-CSF.
      METHODS: Adult male Wistar rats were subjected to photothrombotic ischemia and
      subsequently treated with NaCl, BDNF or G-CSF, respectively. After 6 weeks,
      postischemic protein expression of the NR1, GluR1 and alpha2 subunit of the NMDA,
      AMPA and GABA(A) receptor, respectively, was semiquantitatively determined ipsi-
      and contralateral to the ischemic lesion. Structural plasticity was further
      analyzed immunohistochemically using antibodies against MAP1B, MAP2 and
      synaptophysin. RESULTS: Only BNDF caused a significantly reduced postischemic
      protein expression of the GABA(A) receptor alpha2 subunit and the NR1 subunit of
      the NMDA receptor in the hippocampus. Furthermore, BDNF compared to G-CSF
      increased MAP1B protein expression in the periischemic regenerative region.
      CONCLUSIONS: Although both BDNF and G-CSF have been shown to improve postischemic
      functional outcome to a similar extent, exogenous administration results in
      different underlying structural reorganization processes suggesting specific
      modulations of plasticity-associated events by these trophic factors.

PMID- 19164852
TI  - Systemic delivery of umbilical cord blood cells for stroke therapy: a review.
AB  - PURPOSE: This review paper summarizes relevant studies, discusses potential
      mechanisms of transplanted cell-mediated neuroprotection, and builds a case for
      the need to establish outcome parameters that are critical for transplantation
      success. In particular, we outline the advantages and disadvantages of systemic
      delivery of human umbilical cord blood (HUCB) cells in the field of cellular
      transplantation for treating ischemic stroke. METHODS: A MEDLINE/PubMed
      systematic search of published articles in peer-reviewed journals over the last
      25 years was performed focusing on the theme of HUCB as donor graft source for
      transplantation therapy in neurological disorders with emphasis on stroke.
      RESULTS: Ischemic stroke remains a leading cause of human death and disability.
      Although stroke survivors may gain spontaneous partial functional recovery, they
      often suffer from sensory-motor dysfunction, behavioral/neurological alterations,
      and various degrees of paralysis. Currently, limited clinical intervention is
      available to prevent ischemic damage and restore lost function in stroke victims.
      Stem cells from fetal tissues, bone marrow, and HUCB has emerged in the last few
      years as a potential cell transplant cell source for ischemic stroke, because of
      their capability to differentiate into multiple cell types and the possibility
      that they may provide trophic support for cell survival, tissue repair, and
      functional recovery. CONCLUSION: A growing number of studies highlight the
      potential of systemic delivery of HUCB cells as a novel therapeutic approach for
      stroke. However, additional preclinical studies are warranted to reveal the
      optimal HUCB transplant regimen that is safe and efficacious prior to proceeding
      to large-scale clinical application of these cells for stroke therapy.

PMID- 19164853
TI  - Lasting effects of repeated rTMS application in focal hand dystonia.
AB  - PURPOSE: Focal hand dystonia (FHD) is a rare but potentially devastating disorder
      involving involuntary muscle spasms and abnormal posturing that impairs
      functional hand use. Increased cortical excitability and lack of inhibitory
      mechanisms have been associated with these symptoms. This study investigated the
      short- and long-term effects of repeated administrations of repetitive
      transcranial magnetic stimulation (rTMS) on cortical excitability and handwriting
      performance. METHODS: Six subjects with FHD and nine healthy controls were
      studied. All subjects with FHD received rTMS (1Hz) to the premotor cortex (PMC)
      for five consecutive days; of those, three subjects received five days of sham
      rTMS completed ten days prior to real treatment. Healthy subjects received one
      real rTMS session. Cortical silent period (CSP) and measures of handwriting
      performance were compared before and after treatment and at ten-day post
      treatment follow-up. RESULTS: At baseline, significant differences in CSP and pen
      pressure were observed between subjects with FHD and healthy controls.
      Differences in CSP and pen velocity between subjects in real and sham rTMS groups
      were observed across treatment sessions and maintained at follow-up. CONCLUSIONS:
      After five days of rTMS to PMC, reduced cortical excitability and improved
      handwriting performance were observed and maintained at least ten days following
      treatment in subjects with FHD. These preliminary results support further
      investigation of the therapeutic potential of rTMS in FHD.

PMID- 19164854
TI  - Effects of Schwann cell transplants in an experimental nerve amputee model.
AB  - PURPOSE: By using a nerve amputee model of the rat sciatic nerve (Lago and
      Navarro, 2007), we have tested a strategy for the long-term maintenance of
      regenerated axons without distal target reinnervation, by grafting Schwann cells
      (SCs) into a capped silicone chamber containing the ending nerve stump. METHODS:
      The sciatic nerve of rats was transected and repaired with a silicone tube, the
      distal nerve was again cut at 10 mm and inserted in a capped tube that was filled
      with saline or with a suspension of cultured SCs. Transplants of SCs obtained
      from primary cultures have been compared with those of an immortalized SC line
      (SCTM41) or the same line overexpressing GDNF. RESULTS: The histological results
      show that nerve fibers were able to regenerate through a short distal nerve
      segment ending into the capped chamber, and sustain distal branches without
      degenerating for several months. There was abundant axonal sprouting forming an
      ending neuroma, and the caliber of myelinated fibers remained far thinner than
      normal during the 9 months investigated. With a distal transplant of primary SCs
      there were significantly more regenerated myelinated fibers than in the control
      group at 9 months, indicating that the grafted cells stimulated the axonal growth
      response and helped to maintain survival of axon branches. In contrast, axonal
      regeneration was significantly reduced with grafts of SCTM41 cells, probably due
      to physical competition between cell proliferation and axonal growth. SCTM41
      cells overexpressing GDNF improved the regenerative response with respect to the
      parent SCTM41 cells, although not to the same extent as the primary SCs.
      CONCLUSION: A graft of primary SCs in the capped chamber stimulated axonal growth
      response and/or maintained survival of axonal branches on the long term in the
      nerve amputee model.

PMID- 19164855
TI  - Postreceptor insulin resistance contributes to human dyslipidemia and hepatic
      steatosis.
AB  - Metabolic dyslipidemia is characterized by high circulating triglyceride (TG) and
      low HDL cholesterol levels and is frequently accompanied by hepatic steatosis.
      Increased hepatic lipogenesis contributes to both of these problems. Because
      insulin fails to suppress gluconeogenesis but continues to stimulate lipogenesis
      in both obese and lipodystrophic insulin-resistant mice, it has been proposed
      that a selective postreceptor defect in hepatic insulin action is central to the
      pathogenesis of fatty liver and hypertriglyceridemia in these mice. Here we show
      that humans with generalized insulin resistance caused by either mutations in the
      insulin receptor gene or inhibitory antibodies specific for the insulin receptor
      uniformly exhibited low serum TG and normal HDL cholesterol levels. This was due
      at least in part to surprisingly low rates of de novo lipogenesis and was
      associated with low liver fat content and the production of TG-depleted VLDL
      cholesterol particles. In contrast, humans with a selective postreceptor defect
      in AKT2 manifest increased lipogenesis, elevated liver fat content, TG-enriched
      VLDL, hypertriglyceridemia, and low HDL cholesterol levels. People with
      lipodystrophy, a disorder characterized by particularly severe insulin resistance
      and dyslipidemia, demonstrated similar abnormalities. Collectively these data
      from humans with molecularly characterized forms of insulin resistance suggest
      that partial postreceptor hepatic insulin resistance is a key element in the
      development of metabolic dyslipidemia and hepatic steatosis.

PMID- 19164856
TI  - Identification of a bone marrow-derived epithelial-like population capable of
      repopulating injured mouse airway epithelium.
AB  - The bone marrow compartment is enriched in stem and progenitor cells, and an
      unidentified subpopulation of these cells can contribute to lung epithelial
      repair. Here we identify this subpopulation and quantitate its relative
      contribution to injured airway epithelium. A subpopulation of adherent human and
      murine bone marrow cells that expresses Clara cell secretory protein (CCSP) was
      identified using flow cytometry. When cultured at the air-liquid interface in ex
      vivo cultures, Ccsp+ cells expressed type I and type II alveolar markers as well
      as basal cell markers and active epithelial sodium channels. Ccsp+ cells
      preferentially homed to naphthalene-damaged airways when delivered
      transtracheally or intravenously, with the former being more efficient than the
      latter. Interestingly, naphthalene-induced lung damage transiently increased Ccsp
      expression in bone marrow and peripheral circulation. Furthermore, lethally
      irradiated Ccsp-null mice that received tagged wild-type bone marrow contained
      donor-derived epithelium in both normal and naphthalene-damaged airways. This
      study therefore identifies what we believe to be a newly discovered cell in the
      bone marrow that might have airway reconstitution potential in the context of
      cell-based therapies for lung disease. Additionally, these data could reconcile
      previous controversies regarding the contribution of bone marrow to lung
      regeneration.

PMID- 19164857
TI  - Hedgehog signaling has a protective effect in glucocorticoid-induced mouse
      neonatal brain injury through an 11betaHSD2-dependent mechanism.
AB  - Glucocorticoids (GCs) are administered to human fetuses at risk of premature
      delivery and to infants with life-threatening respiratory and cardiac conditions.
      However, there are ongoing concerns about adverse effects of GC treatment on the
      developing human brain, although the precise molecular mechanisms underlying GC
      induced brain injury are unclear. Here, we identified what we believe to be novel
      cross-antagonistic interactions of Sonic hedgehog (Shh) and GC signaling in
      proliferating mouse cerebellar granule neuron precursors (CGNPs). Chronic GC
      treatment (from P0 through P7) in mouse pups inhibited Shh-induced proliferation
      and upregulation of expression of N-myc, Gli1, and D-type cyclin protein in
      CGNPs. Conversely, acute GC treatment (on P7 only) caused transient apoptosis.
      Shh signaling antagonized these effects of GCs, in part by induction of 11beta
      hydroxysteroid dehydrogenase type 2 (11betaHSD2). Importantly, 11betaHSD2
      antagonized the effects of the GCs corticosterone, hydrocortisone, and
      prednisolone, but not the synthetic GC dexamethasone. Our findings indicate that
      Shh signaling is protective in the setting of GC-induced mouse neonatal brain
      injury. Furthermore, they led us to propose that 11betaHSD2-sensitive GCs (e.g.,
      hydrocortisone) should be used in preference to dexamethasone in neonatal human
      infants because of the potential for reduced neurotoxicity.

PMID- 19164859
TI  - Catheter ablation for atrial fibrillation: what is the necessary and appropriate
      endpoint of the procedure?

PMID- 19164858
TI  - Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3
      inflammasome.
AB  - Hepatocyte death results in a sterile inflammatory response that amplifies the
      initial insult and increases overall tissue injury. One important example of this
      type of injury is acetaminophen-induced liver injury, in which the initial toxic
      injury is followed by innate immune activation. Using mice deficient in Tlr9 and
      the inflammasome components Nalp3 (NACHT, LRR, and pyrin domain-containing
      protein 3), ASC (apoptosis-associated speck-like protein containing a CARD), and
      caspase-1, we have identified a nonredundant role for Tlr9 and the Nalp3
      inflammasome in acetaminophen-induced liver injury. We have shown that
      acetaminophen treatment results in hepatocyte death and that free DNA released
      from apoptotic hepatocytes activates Tlr9. This triggers a signaling cascade that
      increases transcription of the genes encoding pro-IL-1beta and pro-IL-18 in
      sinusoidal endothelial cells. By activating caspase-1, the enzyme responsible for
      generating mature IL-1beta and IL-18 from pro-IL-1beta and pro-IL-18,
      respectively, the Nalp3 inflammasome plays a crucial role in the second step of
      proinflammatory cytokine activation following acetaminophen-induced liver injury.
      Tlr9 antagonists and aspirin reduced mortality from acetaminophen hepatotoxicity.
      The protective effect of aspirin on acetaminophen-induced liver injury was due to
      downregulation of proinflammatory cytokines, rather than inhibition of platelet
      degranulation or COX-1 inhibition. In summary, we have identified a 2-signal
      requirement (Tlr9 and the Nalp3 inflammasome) for acetaminophen-induced
      hepatotoxicity and some potential therapeutic approaches.

PMID- 19164860
TI  - Learning from clinical randomized trials individualized therapy is important in
      the management of atrial fibrillation.

PMID- 19164861
TI  - Inhibition of RhoA or Rac1? Mechanism of cholesterol-independent beneficial
      effects of statins.

PMID- 19164862
TI  - Letter to the editor, "Clinical significance of cerebral oxygenation during
      exercise in patients with coronary artery disease".

PMID- 19164864
TI  - Clinical and ultrasound features of cytology diagnosed follicular neoplasm.
AB  - The purpose of this study was to identify clinical and ultrasound (US) features
      of malignancy in patients using cytological results of follicular neoplasm (FN)
      in the thyroid. We followed 165 patients with cytology diagnosed FN and evaluated
      the final surgical histopathology outcomes in 114 patients between March 2006 and
      November 2008. Patient histopathology, age, sex, tumor size, and US
      characteristics and the color flow pattern of the lesions were analyzed and
      compared between benign and carcinomas. Twenty five (21.9%) of the 114 FN were
      found to be follicular carcinomas (FC); 15 minimally invasive FC, 4 widely
      invasive FC, and 6 FVPTC. Benign included 78 FA, 8 atypical FA, and 3 Hurthle
      cell adenomas. The incidence of malignancy was 31.8% (7/22) in men and 19.6%
      (18/92) in women (p=0.253); and it was similar throughout the different age (<45
      vs. >45) and nodule size groups (<2 cm vs.>2 cm, <4 cm vs. >4 cm). The difference
      of shape, margin, the presence of a halo, internal content, and calcifications
      was not statistically significant (p value =0.05). In malignancy more frequent
      internal central color Doppler flow was present (p=0.030). Color Doppler flow
      pattern of FN with other clinicopathological factors should be carefully
      considered when predicting the malignant potential of FN.

PMID- 19164865
TI  - Adrenal venous sampling (AVS) is essential for detecting unilateral or bilateral
      adrenal lesions in primary aldosteronism.

PMID- 19164866
TI  - Analyses of factors influencing the acute effect of octreotide in growth hormone
      secreting adenomas.
AB  - Somatostatin analogues such as octreotide are used to treat active acromegalic
      patients by reducing serum growth hormone (GH) levels. However, the acute effect
      of octreotide on GH secretion differs among patients. To elucidate factors
      influencing the acute effect of octreotide, we collected data from 56 patients
      with somatotroph adenoma from two institutions. We analyzed the correlation of
      the following factors with the acute effect of octreotide: immunohistochemical
      staining of somatostatin receptor subtype 2A (SSTR 2A), presence of gsp mutation,
      proliferative potentials analyzed by Ki-67 staining index (SI). We found that the
      acute effect of octreotide significantly correlated with two factors: Ki-67 SI
      and the plasma membrane-dominant staining pattern of SSTR 2A. Monovariate
      analysis revealed a statistically significant inverse relation of Ki-67 SI with
      the reduction of GH by octreotide. We assessed the contribution of each factor on
      the acute effect of octreotide by multivariate analysis. Significant multiple
      regression was confirmed with p value of 0.003. Post-test revealed that the
      plasma membrane-dominant staining pattern of SSTR 2A was significantly related to
      the reduction of GH by octreotide. These results show that the acute effect of
      octreotide is positively related to SSTR 2A staining on the plasma membrane.

PMID- 19164867
TI  - A review of food frequency questionnaires developed and validated in Japan.
AB  - BACKGROUND: The food frequency questionnaire (FFQ) has been used throughout the
      world for epidemiological purposes. Because dietary habits vary greatly, the FFQ
      must be tailored for use with specific populations. The usefulness of FFQs in
      Japan was assessed by reviewing questionnaires developed and validated in that
      country. METHODS: A literature search was conducted to identify articles on the
      development and/or validation of FFQs for Japanese populations. For each FFQ
      identified, validation studies were used to abstract its characteristics and
      information. The correlation coefficients between diet records (DRs) and FFQ
      estimates and those between the same FFQs completed twice were used to evaluate
      validity and reproducibility, respectively, of the questionnaires. RESULTS:
      Twenty-one eligible FFQs were identified. They were found to be reasonably valid
      and reproducible. The median of correlation coefficients between DRs and FFQs
      ranged from 0.31 to 0.56 for target nutrients, and that between the same FFQs
      completed twice within a period of 9 months to 1 year ranged from 0.50 to 0.72.
      Relatively poor validity was found for FFQ estimates on consumption of potatoes,
      seaweed, sodium, niacin, and polyunsaturated fatty acids. For the purpose of
      analysis, FFQs were divided into long FFQs (97 or more food items) and short FFQs
      (<70 items); the former had slightly higher validity. CONCLUSION: FFQs are useful
      for assessing dietary intake in Japan, although careful consideration is required
      for the food groups and nutrients for which FFQs had low validity.

PMID- 19164868
TI  - Activities of daily living, functional capacity, and life satisfaction of
      subacute myelo-optico-neuropathy patients in Japan.
AB  - BACKGROUND: Patients with subacute myelo-optico-neuropathy (SMON) suffer from a
      number of serious neurological symptoms that adversely affect their activities of
      daily living (ADL). However, the effects of these neurological symptoms on
      functional capacity and life satisfaction have not been reported. METHODS: We
      analyzed data from 1,300 SMON patients aged 55-94 years that was obtained at
      medical check-ups carried out by the SMON Research Committee in 2004-2006 in
      Japan. The neurological symptoms investigated were visual impairment, dysbasia,
      symptoms of the lower extremities, and sensory symptoms. Neurological symptoms
      were classified by severity. The Barthel Index, the Tokyo Metropolitan Institute
      of Gerontology Index of Competence, and the participant's response to the
      question "Are you satisfied with life?" were used to evaluate ADL, functional
      capacity, and life satisfaction, respectively. Data were analyzed using a
      proportional odds model with the scores for these items as ordinal dependent
      variables. RESULTS: For most neurological symptoms, scores for ADL, functional
      capacity, and life satisfaction were significantly lower in participants with
      severe or moderate neurological symptoms than in those with nearly normal results
      upon examination. The odds ratio for life satisfaction due to superior functional
      capacity was significant after adjustment for sex, age, and ADL score.
      CONCLUSION: The presence of neurological symptoms in SMON patients was associated
      with low functional capacity, life satisfaction, and ADL. Our results suggest
      that the life satisfaction of SMON patients can be increased by improving their
      functional capacity.

PMID- 19164869
TI  - Physical activity and all-cause mortality in Japan: the Jichi Medical School
      (JMS) Cohort Study.
AB  - BACKGROUND: In April 2008, a new health check-up and health guidance system was
      introduced by the Japanese Government to promote increased physical activity.
      However, few studies have documented the health benefits of physical activity in
      Asian populations. We examined the association between all-cause mortality and
      level of physical activity in a Japanese multicommunity population-based study.
      METHODS: The Jichi Medical School Cohort Study is a multicommunity, population
      based study based in 12 districts in Japan. Baseline data from 4222 men and 6609
      women (mean age, 54.8 and 55.0 years, respectively) were collected between April
      1992 and July 1995. The participants were followed for a mean duration of 11.9
      years. To determine the association between all-cause mortality and level of
      physical activity, crude mortality rates per 1000 person-years and hazard ratios
      (HRs) with 95% confidence intervals (CI) were determined using the Cox
      proportional hazards model. Physical activity was categorized by using physical
      activity index (PAI) quartiles. The lowest (first) PAI quartile was defined as
      the HR reference. RESULTS: In men, the lowest mortality rate was observed in the
      third quartile, with 95 deaths and a crude mortality rate of 7.6; the age- and
      area-adjusted HR was 0.59 (95% CI, 0.45-0.76), and the mortality curve had a
      reverse J shape. In women, the lowest mortality rate was observed in the highest
      PAI quartile, with 69 deaths and a crude mortality rate of 3.5; the HR was 0.81
      (95% CI, 0.58-1.12). CONCLUSION: Our results suggest that increased physical
      activity lowers the risk for all-cause death in Japanese.

PMID- 19164870
TI  - Utilization of and direct expenditure for emergency medical care in Taiwan: a
      population-based descriptive study.
AB  - BACKGROUND: We surveyed the emergency medical system (EMS) in Taiwan to provide
      information to policymakers responsible for decisions regarding the
      redistribution of national medical resources. METHODS: A systematic sampling
      method was used to randomly sample a representative database from the National
      Health Insurance (NHI) database in Taiwan, during the period from 2000 to 2004.
      RESULTS: We identified 10,124, 10,408, 11,209, 10,686, and 11,914 emergency room
      visits in 2000, 2001, 2002, 2003, and 2004, respectively. There were more males
      than females, and the majority of adults were younger than 50 years. Diagnose of
      injury/poisoning was the most frequently noted diagnostic category in emergency
      departments (EDs) in Taiwan. There were 13,196 (24.3%) and 2,952 (5.4%) patients
      with 2 and 3 concomitant diagnoses, respectively. There was a significant
      association between advanced age and the existence of multiple diagnoses (P <
      0.001). With the exception of the ill-defined symptoms/signs/conditions, the two
      most frequent diagnoses were diseases of the circulatory system and diseases of
      the respiratory system in patients aged 65 years or older. On average, treatment
      associated expenditure and drug-associated expenditure in Taiwan EDs averaged
      NT$1,155 ($35.0) and NT$190 ($5.8), respectively, which was equal to 64.5% and
      10.6% of the total ED-associated cost. General ED medical expenditure increased
      with patient age; the increased cost ratio due to age was estimated at 8% per
      year (P < 0.001). CONCLUSIONS: The frequency of major health problems diagnosed
      at ED visits varied by age: more complicated complaints and multiple diagnoses
      were more frequent in older patients. In Taiwan, the ED system remains
      overloaded, possibly because of the low cost of an ED visit.

PMID- 19164871
TI  - Increased mortality risk for cancers of the kidney and other urinary organs among
      Chinese herbalists.
AB  - BACKGROUND: A national survey in Taiwan has shown that Chinese herbal therapy
      increases the risk of chronic kidney disease. However, it is unknown whether
      herbal therapy will increase the risk of urological cancers. The purpose of this
      study was to determine whether Chinese herbalists are at higher risk for
      urological cancers. METHODS: We studied all Chinese herbalists in Taiwan that
      were registered in the Chinese Herbalist Labor Union between 1985 and 2000. We
      retrospectively followed their survival status and causes of death using the
      National Mortality Registry Database from 1985 to 2004. Standardized mortality
      ratios (SMRs) for urological cancers in herbalists were calculated and compared
      with those of the general population of Taiwan. RESULTS: A total of 6548 Chinese
      herbalists were enrolled and 88,289 person-years were accrued during the
      observation period. After adjustment for age and sex, the SMR for urological
      cancers was significantly higher for Chinese herbalists than for the general
      population (SMR = 3.10; 95% CI: 1.41-5.87). When further stratified by location,
      the SMR for kidney cancer and other urinary organ cancers (SMR = 3.81; 95% CI:
      1.39-8.28) except bladder cancer (SMR = 2.26; 95% CI: 0.47-6.59) were
      significantly higher for the Chinese herbalists. The SMR for chronic and
      unspecified nephritis, renal failure, and renal sclerosis were also significantly
      higher for herbalists (SMR = 2.40; 95% CI: 1.40-3.84). CONCLUSIONS: Chinese
      herbalists have a significantly higher risk for urological cancers. This
      increased risk among herbalists highlights the urgent need for safety assessments
      of Chinese herbs.

PMID- 19164872
TI  - Personality and gastric cancer screening attendance: a cross-sectional analysis
      from the Miyagi Cohort Study.
AB  - OBJECTIVE: To determine the associations between personality subscales and
      attendance at gastric cancer screenings in Japan. METHODS: A total of 21,911
      residents in rural Japan who completed a short form of the Eysenck Personality
      Questionnaire-Revised (EPQ-R) and a questionnaire on various health habits
      including the number of gastric cancer screenings attended were included in the
      primary analysis. We defined gastric cancer screening compliance as attendance at
      gastric cancer screening every year for the previous 5 years; all other patterns
      of attendance were defined as non-compliance. We defined gastric cancer screening
      visiting as attendance at 1 or more screenings during the previous 5 years; lack
      of attendance was defined as non-visiting. We used logistic regression to
      estimate the odds ratios (ORs) of gastric cancer screening compliance and
      visiting according to 4 score levels that corresponded to the 4 EPQ-R subscales
      (extraversion, neuroticism, psychoticism, and lie). RESULT: Extraversion had a
      significant linear, positive association with both compliance and visiting
      (trend, P < 0.001 for both). Neuroticism had a significant linear, inverse
      association with compliance (trend, P = 0.047), but not with visiting (trend, P =
      0.21). Psychoticism had a significant linear, inverse association with both
      compliance and visiting (trend, P < 0.001 for both). Lie had no association with
      either compliance or visiting. CONCLUSION: The personality traits of
      extraversion, neuroticism, and psychoticism were significantly associated with
      gastric cancer screening attendance. A better understanding of the association
      between personality and attendance could lead to the establishment of effective
      campaigns to motivate people to attend cancer screenings.

PMID- 19164873
TI  - The effect of the interaction between obesity and drinking on hyperuricemia in
      Japanese male office workers.
AB  - BACKGROUND: Obesity and drinking are acknowledged risk factors for hyperuricemia.
      However, the effect of the interaction between obesity and drinking on
      hyperuricemia is not well understood. METHODS: The cases comprised 3028 male
      office workers with hyperuricemia (serum uric acid level >or=7.0 mg/dL); the
      controls were 5348 men with a serum uric acid level less than 6.0 mg/dL. Logistic
      regression analysis was used to assess risk factors for hyperuricemia and the
      interaction between obesity and drinking in hyperuricemia. Participants were
      divided into 2 groups according to their BMI: individuals with a BMI of 25 or
      higher were classified as obese and those with a BMI less than 25 were classified
      as non-obese. In addition, participants were divided into 5 groups based upon
      their ethanol consumption. The 2 variables were then combined to create 10
      groups. RESULTS: With non-obese non-drinkers as the reference category, the odds
      ratio for hyperuricemia was 1.80 for non-obese drinkers of less than 25 mL/day of
      ethanol, 2.15 for non-obese drinkers of 25-49 mL/day, 2.60 for non-obese drinkers
      of 50-74 mL/day, 2.56 for non-obese drinkers of 75+ mL/day, 4.40 for obese non
      drinkers, 5.74 for obese drinkers of less than 25 mL/day, 6.57 for obese drinkers
      of 25-49 mL/day, 5.55 for obese drinkers of 50-74 mL/day, and 7.77 for obese
      drinkers of 75+ mL/day. The interaction between obesity and drinking in
      hyperuricemia was statistically significant. CONCLUSION: Our results suggest that
      although combining the effects of obesity and drinking did not result in a
      multiplicative increase in the risk for hyperuricemia, the combined risk was
      greater than the sum of the effects of obesity and drinking.

PMID- 19164874
TI  - Use of the nuc1 null mutant for analysis of yeast mitochondrial nucleoids.
AB  - Mitochondrial DNA (mtDNA) of the yeast Saccharomyces cerevisiae is organized to
      form mitochondrial nucleoids (mt-nucleoids) by association with specific
      proteins. The sensitivity of DNA-protein complexes to nuclease digestion is a
      useful means for examining DNA packaging and organization. However, the mt
      nucleoids isolated from wild-type cells of S. cerevisiae demonstrated a
      significant amount of endogenous nuclease activity. In order to minimize the
      nuclease activity associated with the isolated mt-nucleoids, we isolated the mt
      nucleoids from a mutant strain that lacked the mitochondrial nuclease, Nuc1p. In
      this manner, we succeeded in isolating mt-nucleoids that showed a low level of
      the nuclease activity. Micrococcal nuclease treatment of these mt-nucleoids led
      to the continuous digestion of mtDNA in the presence of Ca(2+) ions. MtDNA in the
      mt-nucleoids also showed the continuous digestion pattern when treated with DNase
      II. These results suggest that mtDNA in the mt-nucleoids is protected from
      nuclease digestion by association with proteins, but the organization of the
      mtDNA-protein complexes is different from that of nuclear chromatin, in which the
      unit of DNA packaging is regularly repeated.

PMID- 19164875
TI  - Anoxybacillus kamchatkensis subsp. asaccharedens subsp. nov., a thermophilic
      bacterium isolated from a hot spring in Batman.
AB  - A new thermophilic spore-forming strain KG8(T) was isolated from the mud of
      Taslidere hot spring in Batman. Strain KG8(T) was aerobe, Gram-positive, rod
      shaped, motile, occurring in pairs or filamentous. Growth was observed from 35-65
      degrees C (optimum 55 degrees C) and at pH 5.5-9.5 (optimum pH 7.5). It was
      capable of utilizing starch, growth was observed until 3% NaCl (w/v) and it was
      positive for nitrate reduction. On the basis of 16S rRNA gene sequence
      similarity, strain KG8(T) was shown to be related most closely to Anoxybacillus
      species. Chemotaxonomic data (major isoprenoid quinone-menaquinone-7; major fatty
      acid-iso-C15:0 and iso-C17:0) supported the affiliation of strain KG8(T) to the
      genus Anoxybacillus. The results of DNA-DNA hybridization, physiological and
      biochemical tests allowed genotypic and phenotypic differentiation of strain
      KG8(T). Based on these results we propose assigning a novel subspecies of
      Anoxybacillus kamchatkensis, to be named Anoxybacillus kamchatkensis subsp.
      asaccharedens subsp. nov. with the type strain KG8(T) (DSM 18475(T)=CIP
      109280(T)).

PMID- 19164876
TI  - Actinomadura maheshkhaliensis sp. nov., a novel actinomycete isolated from
      mangrove rhizosphere soil of Maheshkhali, Bangladesh.
AB  - The taxonomic position of one soil isolate 13-12(50)(T) was clarified by a
      polyphasic study. The organism showed a combination of chemotaxonomic and
      morphological properties typical of the genus Actinomadura. It formed a distinct
      phyletic line in the Actinomadura 16S rRNA gene tree and was closely associated
      with Actinomadura mexicana (sequence similarity 99.5%), Actinomadura glauciflava,
      Actinomadura citrea (sequence similarity 99.4%) and Actinomadura madurae
      (sequence similarity 99.2%). The result of DNA-DNA hybridizations between 13
      12(50)(T) and Actinomadura mexicana was 49.9%. On the basis of the phenotypic,
      chemotaxonomic and genotypic properties, the isolate was differentiated from its
      closest phylogenetic relatives. It is proposed that the organism be classified as
      a novel species of the genus Actinomadura. The name proposed for the new taxa are
      Actinomadura maheshkhaliensis sp. nov. [(13-12(50)(T)=JCM 13934(T) =MTCC
      8055(T)].

PMID- 19164877
TI  - Codon optimization prevents premature polyadenylation of heterologously-expressed
      cellulases from termite-gut symbionts in Aspergillus oryzae.
AB  - To achieve high expression of glycoside hydrolase family 45 endoglucanase
      (RsSym45EG1) from a symbiotic protist of the termite Reticulitermes speratus,
      synthetic sequence RsSym45eg1-co, in which the codon usage was adjusted to that
      of the highly-expressed tef1 gene encoding translation elongation factor 1alpha,
      was prepared and introduced into A. oryzae. The transcript level of RsSym45eg1-co
      was 1.8-fold higher than that of RsSym45eg1. In cells harboring RsSym45eg1, but
      not RsSym45eg1-co, truncated transcripts in which the coding region was
      prematurely terminated and followed by a poly A chain were found. The production
      of endoglucanase in the culture supernatant was improved by codon optimization.
      Truncated transcripts were also found when cellobiohydrolase and beta-glucosidase
      from R. speratus symbionts were expressed, and the transcript level of the former
      was increased by codon-optimization. Our findings suggest that premature
      polyadenylation frequently occurs in heterologous protein expression in A.
      oryzae, which might result in the poor yield of expressed proteins.

PMID- 19164878
TI  - Ogataea neopini sp. nov. and O. corticis sp. nov., with the emendation of the
      ascomycete yeast genus Ogataea, and transfer of Pichia zsoltii, P. dorogensis,
      and P. trehaloabstinens to it.
AB  - During a survey of yeast strains having high conversion efficiency to ethanol
      from cellobiose, 'Ogataea pini' ATCC 28781 and 'Pichia pini' NBRC 1794 were found
      to be distinct from any known species and from each other by a BLAST homology
      search using the D1/D2 LSU rRNA gene sequences. The D1/D2 phylogeny showed that
      'O. pini' ATCC 28781 and 'P. pini' NBRC 1794 belonged to the Ogataea cluster,
      whereas a comparison of the ITS 1 and 2 regions sequences showed that the ATCC
      and NBRC strains each formed a species distinct from O. ganodermae, O. pini, O.
      henricii, and P. zsoltii, based on the D1/D2 sequence divergence. The ATCC and
      NBRC strains formed two to four hat-shaped ascospores and two to four, or more
      ones per deliquescent ascus, respectively, were negative for DBB and urease
      reactions, assimilated methanol slowly and nitrate not at all, and had the major
      ubiquinone system Q-7. These characteristics coincided basically with the
      definition of Ogataea proposed by Yamada et al. in 1994, excluding the number of
      ascospores. On the other hand, the ATCC and NBRC strains differed not only from
      each other but from relatives in various phenotypic characteristics. These
      differences suggest that two new yeasts of Ogataea be described as novel. The new
      species and their type strains are as follows: O. neopini ATCC 28781(T); and O.
      corticis NBRC 1794(T). In addition, the emendation of the genus Ogataea is made;
      besides, we propose the transfer of P. zsoltii, P. dorogensis, and P.
      trehaloabstinens, which were placed in the Ogataea cluster based on the D1/D2
      sequence analysis, to the genus Ogataea as O. zsoltii comb. nov., O. dorogensis
      comb. nov., and O. trehaloabstinens comb. nov.

PMID- 19164879
TI  - The pOT and pLOB vector systems: improving ease of transgene expression in
      Botrytis cinerea.
AB  - This paper outlines the construction of a novel vector system comprising
      interchangeable terminators, as well as a multiple cloning site (MCS), to
      facilitate the transformation of the fungal plant pathogen Botrytis cinerea.
      Previous molecular studies on B. cinerea have relied upon the pLOB1 based vector
      system (controlled by the Aspergillus nidulans oliC promoter and a region
      reported to be the B. cinerea tubA terminator). Investigations, however, have
      revealed that, rather than the genuine B. cinerea tubA terminator, the pLOB1
      terminator fragment is from another gene locus within the genome. Because
      previous studies have found that terminators aide in transcript stability, the
      main aims of this study were to develop and evaluate both vector systems, pOT
      (controlled by the A. nidulans oliC promoter and A. nidulans trpC terminator) and
      pLOB, with a range of exogenous genes, including enhanced green fluorescent
      protein (eGFP), monomeric red fluorescent protein (mRFP), luciferase (LUC) and
      beta-glucuronidase (GUS). Our investigations demonstrate that pLOB and pOT based
      vectors are capable of expressing all four reporter genes and may be applied to
      future molecular studies on B. cinerea and other related ascomycetes.
      Additionally, this is the first reported expression of mRFP and LUC in B.
      cinerea.

PMID- 19164880
TI  - Ogataea paradorogensis sp. nov., a novel methylotrophic ascomycetous yeast
      species isolated from galleries of ambrosia beetles in Japan, with a close
      relation to Pichia dorogensis.
AB  - Two yeast strains isolated from galleries of ambrosia beetles in Japan and
      maintained in NITE Biological Resource Center (NBRC) as Pichia pini were found to
      represent a hitherto undescribed species. This species shows close relationship
      to Pichia dorogensis by the sequence analysis of the D1/D2 domain of 26S rDNA but
      is clearly differentiated from it by a DNA-DNA reassociation experiment. It is
      described as Ogataea paradorogensis sp. nov. The vegetative cells and asci of
      this species are surrounded with distinct capsules like P. dorogensis. One to
      four hat-shaped ascospores, which tend to be liberated from the asci at
      maturation, are formed in the ascus.

PMID- 19164881
TI  - A cold-active extracellular metalloprotease from Curtobacterium luteum (MTCC
      7529): enzyme production and characterization.
AB  - A novel psychro-tolerant bacterium, Curtobacterium luteum, secreting an
      extracellular protease was isolated from the soil of Gangotri glacier, Western
      Himalaya. Maximum enzyme production was achieved when the strain was grown in a
      pH-neutral medium containing skim milk at 15 degrees C over 120 h. The metal ions
      such as Zn(2+) and Cr(2+) enhanced enzyme production. The specific activity of
      purified enzyme was 8,090 units/mg after 34.1-fold purification. The 115 kDa
      enzyme was a metalloprotease (activity inhibited by EDTA and EGTA) and showed
      maximum activity at 20 degrees C and pH 7. The enzyme was active over a broad pH
      range and retained 84% of its original activity between pH 6 and 8. There was no
      loss in enzyme activity when exposed for 3 h at 4-20 degrees C. However, the
      enzyme lost 65% of activity at 30 degrees C, and was almost inactivated at 50
      degrees C, but was resistant to repeated freezing and thawing. The enzyme
      activity was stimulated by manganese ions; however, it was inactivated by copper
      ions.

PMID- 19164882
TI  - Functional expression of LZ-8, a fungal immunomodulatory protein from Ganoderma
      lucidium in Pichia pastoris.
AB  - LZ-8, a fungal immunomodulatory protein found in Ganoderma lucidium, has been
      proposed to have therapeutic effects on cancer and autoimmune diseases. To
      develop an efficient and facile expression system supplying of rLZ-8 of high
      purity and stable activity for further study and applications, a full-length cDNA
      of lz8 gene was cloned into the pPIC9K to construct a yeast expression vector
      pPIC9K-lz8, then transformed to Pichia pastoris strain GS115. The molecular
      weight of the rLZ-8 was about 17 kDa. The yield of rLZ-8 reached up to 270 mg L(
      1) at optimal culture conditions. In vitro, the rLZ-8 was capable of
      hemagglutinating mouse red blood cells, but no such activity was observed toward
      human red blood cells, which were similar to the native LZ-8. The mouse
      splenocyte proliferation activity of rLZ-8 expressed in P. pastoris was much
      higher than the rLZ-8 expressed in E. coli. All these results suggested that the
      active rLZ-8 protein can be expressed efficiently in the P. pastoris expression
      system. This report may supply a new economic and convenient way for the
      application of LZ-8 protein.

PMID- 19164883
TI  - Isolation and characterization of bacterial strains Paenibacillus sp. and
      Bacillus sp. for kraft lignin decolorization from pulp paper mill waste.
AB  - Eight aerobic bacterial strains were isolated from pulp paper mill waste and
      screened for tolerance of kraft lignin (KL) using the nutrient enrichment
      technique in mineral salt media (MSM) agar plate (15 g/L) amended with different
      concentrations of KL (100, 200, 300, 400, 500, 600 ppm) along with 1% glucose and
      0.5% peptone (w/v) as additional carbon and nitrogen sources. The strains ITRC S6
      and ITRC S8 were found to have the most potential for tolerance of the highest
      concentration of KL. These organisms were characterized by biochemical tests and
      further 16S rRNA gene (rDNA) sequencing, which showed 96.5% and 95% sequence
      similarity of ITRC S(6) and ITRC S(8) and confirmed them as Paenibacillus sp. and
      Bacillus sp., respectively. KL decolorization was routinely monitored with a
      spectrophotometer and further confirmed by HPLC analysis. Among eight strains,
      ITRC S(6) and ITRC S(8) were found to degrade 500 mg/L of KL up to 47.97% and
      65.58%, respectively, within 144 h of incubation in the presence of 1% glucose
      and 0.5% (w/v) peptone as a supplementary source of carbon and nitrogen. In the
      absence of glucose and peptone, these bacteria were unable to utilize KL. The
      analysis of lignin degradation products by GC-MS analysis revealed the formation
      of various acids as lignin monomers which resulted in a decrease in pH and a
      major change in the chromatographic profile of the bacterial degraded sample as
      compared to the control clear indications of biochemical modification of KL due
      to the bacterial ligninolytic system by ITRC S(6), namely, acetic acid, propanoic
      acid, butanoic acid, guaiacol, hexanoic acid, and ITRC S(8), namely acetic acid,
      propanoic acid, ethanedioic acid, furan carboxylic acid, 2-propanoic acid,
      butanoic acid, 3-acetoxybutyric acid, propanedioic acid, acetoguiacone, 1,2,3
      thiadiazole, 5-carboxaldixime, 4-hydroxy-3,5-dimethoxyphenol, and dibutyl
      phthalate, indicating the bacterium characteristic to degrade G and S units of
      lignin polymer.

PMID- 19164884
TI  - Phylogenetic analysis of Troglodytella abrassarti isolated from Chimpanzees (Pan
      troglodytes verus) in the wild and in captivity.

PMID- 19164885
TI  - Effects of red light emitting diode on apoptosis of HeLa cells and suppression of
      implanted HeLa cells growth in mice.
AB  - Low intensity irradiation of cells by laser was an effective method of
      biostimulation. Here, we have extended these actions to evaluate the apoptosis
      effects in red light emitting diode (RLED) exposure. Through morphological
      observation, flow cytometric analysis, intracellular calcium measurement and RT
      PCR, we found that HeLa cells in 24 h RLED irradiation in in-vitro experiments
      would significantly affects the induction of cellular apoptosis, and
      morphological changes such as the loose arrangement of cells, the noticeable
      development of apoptotic bodies,and the accompaniment of arrested S phase and
      activated caspases-3,-6,-8. Moreover, intracellular calcium concentrations
      markedly increased 40.3 +/- 1.3% and 43.1 +/- 0.8% respectively, relative to an
      extracellular solution containing the Ca(2+) and Ca(2+) free unexposed group. In
      in-vivo tests, RLED irradiation decreased the growth of tumors on day 50 and
      attenuated the elevation of vascular endothelial growth factor (VEGF) expression
      in HeLa cell implanted BALB/c mice. Taken together, our results suggest that RLED
      could induce HeLa cell apoptosis and convey potential antitumor properties.

PMID- 19164886
TI  - Direct detection of disease associated prions in brain and lymphoid tissue using
      antibodies recognizing the extreme N terminus of PrPC.
AB  - A simple diagnostic test is described for the detection of TSE in bovine, ovine
      and human brain and lymphoid tissue that obviates the use of proteinase K as a
      discriminating reagent. The immunoassay utilises high affinity anti-peptide
      antibodies that appear blind to the normal isoform of prion protein (PrP(C)).
      These reagents have been produced with novel N-terminal chimeric peptides and we
      hypothesise that the retention and stability of the extreme N-terminus of PrP in
      the disease-associated aggregate makes it an operationally specific marker for
      TSE. Accordingly, the assay involves homogenisation of the tissue directly in 8M
      guanidine hydrochloride, a simple one-step capture of PrP(Sc) followed by
      detection with a europium-labelled anti-PrP(C) antibody. This rapid assay clearly
      differentiates between levels of disease-associated PrP extracted from brain and
      lymphoid tissues taken from confirmed TSE positive and negative cattle and sheep.
      The assay can also be used to detect PrP(Sc) in cases of vCJD.

PMID- 19164887
TI  - Preformed cell structure and cell heredity.
AB  - This review will first recall the phenomena of "cortical inheritance" observed
      and genetically demonstrated in Paramecium 40 years ago, and later in other
      ciliates (Tetrahymena, Oxytricha, Paraurostyla), and will analyze the deduced
      concept of "cytotaxis" or "structural memory." The significance of these
      phenomena, all related (but not strictly restricted) to the properties of ciliary
      basal bodies and their mode of duplication, will be interpreted in the light of
      present knowledge on the mechanism and control of basal body/centriole
      duplication. Then other phenomena described in a variety of organisms will be
      analyzed or mentioned which show the relevance of the concept of cytotaxis to
      other cellular processes, mainly (1) cytoskeleton assembly and organization with
      examples on ciliates, trypanosome, mammalian cells and plants, and (2)
      transmission of polarities with examples on yeast, trypanosome and metazoa.
      Finally, I will discuss some aspects of this particular type of non-DNA
      inheritance: (1) why so few documented examples if structural memory is a basic
      parameter in cell heredity, and (2) how are these phenomena (which all rely on
      protein/protein interactions, and imply a formatting role of preexisting
      proteinic complexes on neo-formed proteins and their assembly) related to prions?

PMID- 19164888
TI  - H-type bovine spongiform encephalopathy: complex molecular features and
      similarities with human prion diseases.
AB  - We previously reported that some cattle affected by bovine spongiform
      encephalopathy (BSE) showed distinct molecular features of the protease-resistant
      prion protein (PrP(res)) in Western blot, with a 1-2 kDa higher apparent
      molecular mass of the unglycosylated PrP(res) associated with labelling by
      antibodies against the 86-107 region of the bovine PrP protein (H-type BSE). By
      Western blot analyses of PrP(res), we now showed that the essential features
      initially described in cattle were observed with a panel of different antibodies
      and were maintained after transmission of the disease in C57Bl/6 mice. In
      addition, antibodies against the C-terminal region of PrP revealed a second, more
      C-terminally cleaved, form of PrP(res) (PrP(res) #2), which, in unglycosylated
      form, migrated as a approximately 14 kDa fragment. Furthermore, a PrP(res)
      fragment of approximately 7 kDa, which was not labelled by C-terminus-specific
      antibodies and was thus presumed to be a product of cleavage at both N- and C
      terminal sides of PrP protein, was also detected. Both PrP(res) #2 and
      approximately 7 kDa PrP(res) were detected in cattle and in C57Bl/6 infected
      mice. These complex molecular features are reminiscent of findings reported in
      human prion diseases. This raises questions regarding the respective origins and
      pathogenic mechanisms in prion diseases of animals and humans.

PMID- 19164890
TI  - From molecular tumors to protein genes and back.

PMID- 19164891
TI  - Prions and related phenomena.

PMID- 19164889
TI  - Protein misfolding and the serpinopathies.
AB  - The serpins are the largest superfamily of protease inhibitors. They are found in
      almost all branches of life including viruses, prokaryotes and eukaryotes. They
      inhibit their target protease by a unique mechanism that involves a large
      conformational transition and the translocation of the enzyme from the upper to
      the lower pole of the protein. This complex mechanism, and the involvement of
      serpins in important biological regulatory processes, makes them prone to
      mutation-related diseases. For example the polymerization of mutant alpha(1)
      antitrypsin leads to the accumulation of ordered polymers within the endoplasmic
      reticulum of hepatocytes in association with cirrhosis. An identical process in
      the neuron specific serpin, neuroserpin, results in the accumulation of polymers
      in neurons and the dementia FENIB. In both cases there is a clear correlation
      between the molecular instability, the rate of polymer formation and the severity
      of disease. A similar process underlies the hepatic retention and plasma
      deficiency of antithrombin, C1 inhibitor, alpha(1)-antichymotrypsin and heparin
      co-factor II. The common mechanism of polymerization has allowed us to group
      these conditions together as a novel class of disease, the serpinopathies.

PMID- 19164892
TI  - Self assembly of short aromatic peptides into amyloid fibrils and related
      nanostructures.
AB  - The formation of amyloid fibrils is the hallmark of more than twenty human
      disorders of unrelated etiology. In all these cases, ordered fibrillar protein
      assemblies with a diameter of 7-10 nm are being observed. In spite of the great
      clinical important of amyloid-associated diseases, the molecular recognition and
      self-assembly processes that lead to the formation of the fibrils are not fully
      understood. One direction to decipher the mechanism of amyloid formation is the
      use of short peptides fragments as model systems. Short peptide fragments, as
      short as pentapeptides, were shown to form typical amyloid assemblies in vitro
      that have ultrastructural, biophysical, and cytotoxic properties, as those of
      assemblies that are being formed by full length polypeptides. When we analyzed
      such short fragments, we identified the central role of aromatic moieties in the
      ability to aggregate into ordered nano-fibrillar structures. This notion allowed
      us to discover additional very short amyloidogenic peptides as well as other
      aromatic peptide motifs, which can form various assemblies at the nano-scale
      (including nanotubes, nanospheres, and macroscopic hydrogels with nano-scale
      order). Other practical utilization of this concept, together with novel beta
      breakage methods, is their use for the development of novel classes of amyloid
      formation inhibitors.

PMID- 19164894
TI  - Cathepsin L mediates resveratrol-induced autophagy and apoptotic cell death in
      cervical cancer cells.
AB  - Cathepsins have long been considered as housekeeping molecules. However, specific
      functions have also been attributed to each of these lysosomal proteases.
      Squamous cell carcinoma antigen (SCCA) 1, widely expressed in various uterine
      cervical cells, is an endogenous cathepsin (cat) L inhibitor. In this study, we
      investigated whether the cat L-SCCA 1 lysosomal pathway and autophagy were
      involved in resveratrol (RSV)-induced cytotoxicity in cervical cancer cells. RSV
      induced GFP-LC3 aggregation as well as increased the presence of LC3-II and
      autophagosomes as was revealed by electron microscopy in cervical cancer cells.
      Prolonged treatment of RSV induced cytosolic translocation of cytochrome c,
      caspase 3 activation and apoptotic cell death. This apoptotic effect was
      abrogated by trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane, an inhibitor
      of cat B and L, but not by pepstatin A, an inhibitor of cat D. As cervical cancer
      cells express little cat B, we further studied the role of cat L. RSV induced
      dissipation of the lysosomal membrane permeability (LMP), leakage and increased
      cytosolic expression and activity of cat L. Inhibition of cat L by small
      interference RNA (siRNA) protected cells from RSV-induced cytotoxicity. In
      contrast, inhibition of SCCA 1 by siRNA promoted RSV-induced cytotoxicity.
      Inhibition of autophagic response by wortmannin (WT) or asparagine (ASP) resulted
      in decreased early LC3-II formation, reduced LMP, and abolishment of the increase
      in RSV-induced cell death. In conclusion, we have identified a new cytotoxic
      mechanism in which the lysosomal enzyme cat L acts as a death signal integrator
      in cervical cancer cells. Furthermore, SCCA 1 may play an antiapoptotic role
      through anti-cat L activity.

PMID- 19164893
TI  - Prion-prion interactions.
AB  - The term prion has been used to describe self-replicating protein conformations
      that can convert other protein molecules of the same primary structure into its
      prion conformation. Several different proteins have now been found to exist as
      prions in Saccharomyces cerevisiae. Surprisingly, these heterologous prion
      proteins have a strong influence on each others' appearance and propagation,
      which may result from structural similarity between the prions. Both positive and
      negative effects of a prion on the de novo appearance of a heterologous prion
      have been observed in genetic studies. Other examples of reported interactions
      include mutual or unilateral inhibition and destabilization when two prions are
      present together in a single cell. In vitro work showing that one purified prion
      stimulates the conversion of a purified heterologous protein into a prion form,
      suggests that facilitation of de novo prion formation by heterologous prions in
      vivo is a result of a direct interaction between the prion proteins (a cross
      seeding mechanism) and does not require other cellular components. However, other
      cellular structures, e.g., the cytoskeleton, may provide a scaffold for these
      interactions in vivo and chaperones can further facilitate or inhibit this
      process. Some negative prion-prion interactions may also occur via a direct
      interaction between the prion proteins. Another explanation is a competition
      between the prions for cellular factors involved in prion propagation or
      differential effects of chaperones stimulated by one prion on the heterologous
      prions.

PMID- 19164895
TI  - Prion sequence polymorphisms and chronic wasting disease resistance in Illinois
      white-tailed deer (Odocoileus virginianus).
AB  - Nucleic acid sequences of the prion gene (PRNP) were examined and genotypes
      compiled for 76 white-tailed deer from northern Illinois, which previously tested
      positive for chronic wasting disease (CWD), and 120 negative animals selected to
      control for geographic location and age. Nine nucleotide polymorphisms, seven
      silent and two coding, were found in the sampled population. All observed
      polymorphisms except two of very low frequency were observed in both negative and
      positive animals, although five polymorphic loci had significantly different
      distributions of alleles between infected and non-infected individuals.
      Nucleotide base changes 60C/T, 285A/C, 286G/A and 555C/T were observed with
      higher than expected frequencies in CWD negative animals suggesting disease
      resistance, while 153C/T was observed more than expected in positive animals,
      suggesting susceptibility. The two coding polymorphisms, 285A/C (Q95H) and 286G/A
      (G96S), have been described in white-tailed deer populations sampled in Colorado
      and Wisconsin. Frequency distributions of coding polymorphisms in Wisconsin and
      Illinois deer populations were different, an unexpected result considering the
      sampled areas are less than 150 km apart. The total number of polymorphisms per
      animal, silent or coding, was negatively correlated to disease status. The
      potential importance of silent polymorphisms (60C/T, 153C/T, 555C/T), either
      individually or cumulatively, in CWD disease status has not been previously
      reported.

PMID- 19164896
TI  - Prion-dependent lethality of sup45 mutants in Saccharomyces cerevisiae.
AB  - In yeast Saccharomyces cerevisiae translation termination factors eRF1 (Sup45)
      and eRF3 (Sup35) are encoded by the essential genes SUP45 and SUP35 respectively.
      Heritable aggregation of Sup35 results in formation of the yeast prion [PSI(+)].
      It is known that combination of [PSI(+)] with some mutant alleles of the SUP35 or
      SUP45 genes in one and the same haploid yeast cell causes synthetic lethality. In
      this study, we perform detailed analysis of synthetic lethality between various
      sup45 nonsense and missense mutations on one hand, and different variants of
      [PSI(+)] on the other hand. Synthetic lethality with sup45 mutations was detected
      for [PSI(+)] variants of different stringencies. Moreover, we demonstrate for the
      first time that in some combinations, synthetic lethality is dominant and occurs
      at the postzygotic stage after only a few cell divisions. The tRNA suppressor
      SUQ5 counteracts the prion-dependent lethality of the nonsense alleles but not of
      the missense alleles of SUP45, indicating that the lethal effect is due to the
      depletion of Sup45. Synthetic lethality is also suppressed in the presence of the
      C-proximal fragment of Sup35 (Sup35C) that lacks the prion domain and cannot be
      included into the prion aggregates. Remarkably, the production of Sup35C in a
      sup45 mutant strain is also accompanied by an increase in the Sup45 levels,
      suggesting that translationally active Sup35 up-regulates Sup45 or protects it
      from degradation.

PMID- 19164897
TI  - Prion stability.
AB  - The rate of spontaneous change from psi(-) to the psi(+) condition, determined in
      yeast by states of the Sup35p protein, is briefly discussed together with the
      conditions necessary for such change to occur. Conditions that promote and which
      affect the rate of induction of psi(+) in Sup35p and of other prion-forming
      proteins to their respective prion forms are also discussed. These include the
      influence of the amount of non-prion protein, the presence of other prions, the
      activity of chaperones, and brief descriptions of the role of native sequences in
      the proteins and how alteration of sequences in prion-forming proteins influences
      the rate of induction of [prion(+)] and amyloid forms. The second part of this
      article discusses the conditions which affect the reversion of psi(+) to psi-,
      including factors which affect the copy-number of prion "seeds" or propagons and
      their partition. The principal factor discussed is the activity of the chaperone
      Hsp104, but the existence of other factors, such protein sequence and of other,
      less well-studied agents is touched upon and comparisons are made, as
      appropriate, with studies with other yeast prions. We conclude with a discussion
      of models of maintenance, in particular that of Tanaka et al. published in Nature
      (2006), which provides much insight into the phenotypic and genetic parameters of
      the numerous "variants" of prions increasingly being described in the literature.

PMID- 19164898
TI  - DNA methylation and aberrant expression of Sprouty1 in human prostate cancer.
AB  - Sprouty1 is a negative regulator of fibroblast growth factor signaling with a
      potential tumor suppressor function in prostate cancer (PCa). Sprouty1 is
      downregulated in human PCa and Sprouty1 expression can markedly inhibit PCa
      proliferation in vitro. The aim of this study was to investigate the role of DNA
      methylation in Sprouty1 expression in human prostate tumors. We used
      pyrosequencing to quantitatively measure the methylation status of the Sprouty1
      promoter region in prostate tissues and cell lines and assessed Sprouty1 mRNA
      expression by quantitative RT-PCR. Our data demonstrates significantly higher %
      methylation of Sprouty1 promoter in the PCa tissues when compared to matched
      normal tissues. Hypermethylation of Sprouty1 promoter was detected in PCa cell
      lines compared to the normal prostate epithelial cells. The increased %
      methylation was associated with reduced Sprouty1 mRNA expression in the PCa
      tissues and cell lines. Methylation modification of the Sprouty1 promoter using
      Sss1 methylase abolished promoter activity whereas global demethylation with 5'
      Aza-2'-Deoxycytidine treatment induced Sprouty1 expression. Our data demonstrates
      that DNA methylation in the Sprouty1 promoter region is responsible for
      downregulating Sprouty1 expression in prostate cancer.

PMID- 19164899
TI  - Prion and nonprion amyloids: a comparison inspired by the yeast Sup35 protein.
AB  - Yeast prion determinants are related to polymerization of some proteins into
      amyloid-like fibers. The [PSI(+)] determinant reflects polymerization of the
      Sup35 protein. Fragmentation of prion polymers by the Hsp104 chaperone represents
      a key step of the prion replication cycle. The frequency of fragmentation varies
      depending on the structure of the prion polymers and defines variation in the
      prion phenotypes, e.g., the suppressor strength of [PSI(+)] and stability of its
      inheritance. Besides [PSI(+)], overproduction of Sup35 can produce nonheritable
      phenotypically silent Sup35 amyloid-like polymers. These polymers are fragmented
      poorly and are present due to efficient seeding with the Rnq1 prion polymers,
      which occurs by several orders of magnitude more frequently than seeding of
      [PSI(+)] appearance. Such Sup35 polymers resemble human nonprion amyloids by
      their nonheritability, mode of appearance and increased size. Thus, a single
      protein, Sup35, can model both prion and nonprion amyloids. In yeast, these
      phenomena are distinguished by the frequency of polymer fragmentation. We argue
      that in mammals the fragmentation frequency also represents a key factor defining
      differing properties of prion and nonprion amyloids, including infectivity. By
      analogy with the Rnq1 seeding of nonheritable Sup35 polymers, the "species
      barrier" in prion transmission may be due to seeding by heterologous prion of
      nontransmissible type of amyloid, rather than due to the lack of seeding.

PMID- 19164900
TI  - Apoptosis versus cell differentiation: role of heat shock proteins HSP90, HSP70
      and HSP27.
AB  - Heat shock proteins HSP27, HSP70 and HSP90 are molecular chaperones whose
      expression is increased after many different types of stress. They have a
      protective function helping the cell to cope with lethal conditions. The
      cytoprotective function of HSPs is largely explained by their anti-apoptotic
      function. HSPs have been shown to interact with different key apoptotic proteins.
      As a result, HSPs can block essentially all apoptotic pathways, most of them
      involving the activation of cystein proteases called caspases. Apoptosis and
      differentiation are physiological processes that share many common features, for
      instance, chromatin condensation and the activation of caspases are frequently
      observed. It is, therefore, not surprising that many recent reports imply HSPs in
      the differentiation process. This review will comment on the role of HSP90, HSP70
      and HSP27 in apoptosis and cell differentiation. HSPs may determine de fate of
      the cells by orchestrating the decision of apoptosis versus differentiation.

PMID- 19164901
TI  - Susceptibility of cell substrates to PrPSc infection and safety control measures
      related to biological and biotherapeutical products.
AB  - Concerns over the potential for infectious prion proteins to contaminate human
      biologics and biotherapeutics have been raised from time to time. Transmission of
      the pathogenic form of prion protein (PrP(Sc)) through veterinary vaccines has
      been observed, yet no human case through the use of vaccine products has been
      reported. However, iatrogenic transmissions of PrP(Sc) in humans through blood
      components, tissues and growth hormone have been reported. These findings
      underscore the importance of reliable detection or diagnostic methods to prevent
      the transmission of prion diseases, given that the number of asymptomatic
      infected individuals remains unknown, the perceived incubation time for human
      prion diseases could be decades, and no cure of the diseases has been found yet.
      A variety of biochemical and molecular methods can selectively concentrate
      PrP(Sc) to facilitate its detection in tissues and cells. Furthermore, some
      methods routinely used in the manufacturing process of biological products have
      been found to be effective in reducing PrP(Sc) from the products. Questions
      remain unanswered as to the validation criteria of these methods, the minimal
      infectious dose of the PrP(Sc) required to cause infection and the susceptibility
      of cells used in gene therapy or the manufacturing process of biological products
      to PrP(Sc) infections. Here, we discuss some of these challenging issues.

PMID- 19164902
TI  - Toxic effects of intracerebral PrP antibody administration during the course of
      BSE infection in mice.
AB  - The absence of specific immune response is a hallmark of prion diseases. However,
      in vitro and in vivo experiments have provided evidence that an anti-PrP humoral
      response could have beneficial effects. Prophylactic passive immunization
      performed at the time of infection delayed or prevented disease. Nonetheless, the
      potential therapeutic effect of PrP antibodies administered shortly before the
      clinical signs has never been tested in vivo. Moreover, a recent study showed the
      potential toxicity of PrP antibodies administered intracerebrally. We aimed at
      evaluating the effect of a prolonged intracerebral anti-PrP antibody
      administration at the time of neuroinvasion in BSE infected Tg20 mice.
      Unexpectedly, despite a good penetration of the antibodies in the brain
      parenchyma, the treatment was not protective against the development of BSE.
      Instead, it led to an extensive neuronal loss, strong astrogliosis and microglial
      activation. Since this effect was observed after injection of anti-PrP antibodies
      as whole IgGs, F(ab')(2) or Fab fragments, the toxicity was directly related to
      the ability of the antibodies to recognize native PrP and to the intracerebral
      concentration achieved, and not to the Fc portion or the divalence of the
      antibodies. This experiment shows that a prolonged treatment with anti-PrP
      antibodies by the intracerebral route can induce severe side-effects and calls
      for caution with regard to the use of similar approaches for late therapeutic
      interventions in humans.

PMID- 19164903
TI  - Tau aggregation in Alzheimer's disease: what role for phosphorylation?
AB  - The crucial role of the neuronal Tau protein in microtubule stabilization and
      axonal transport suggests that too little or too much Tau might lead to neuronal
      dysfunction. The presence of a hyper phosphorylated but non aggregated molecule
      as a toxic species that might sequester normal Tau is discussed. We present
      recent in vitro results that might allow us to dissect the role of individual
      phosphorylation sites on its structure and function. We also discuss in this
      review the role of phosphorylation for the aggregation of the neuronal Tau
      protein, and compare it to the aggregation induced by external poly anions.

PMID- 19164904
TI  - Infectious fold and amyloid propagation in Podospora anserina.
AB  - Amyloid protein aggregation is involved in serious neurodegenerative disorders
      such as Alzheimer's disease and transmissible encephalopathies. The concept of an
      infectious protein (prion) being the scrapie agent was successfully validated for
      several yeast and fungi proteins. Ure2, Sup35 and Rnq1 in Saccharomyces
      cerevisiae and HET-s in Podospora anserina have been genetically and
      biochemically identified as prion proteins. Studies on these proteins have
      revealed critical information on the mechanisms of prions appearance and
      propagation. The prion phenotype correlates with the aggregation state of these
      particular proteins. In vitro, the recombinant prion proteins form amyloid fibers
      characterized by rich beta sheet content. In a previous work on the HET-s prion
      protein Podospora, we demonstrated the infectivity of HET-s recombinant amyloid
      aggregates. More recently, the structural analysis of the HET-s prion domain
      associated with in vivo mutagenesis allowed us to propose a model for the
      infectious fold of the HET-s prion domain. Further investigations to complete
      this model are discussed in this review, as are relevant questions about the [Het
      s] system of Podospora anserina.

PMID- 19164905
TI  - A new year, a new role for p21.

PMID- 19164906
TI  - Survivin(g) phosphorylation?

PMID- 19164907
TI  - New TGF-beta and Ras crosstalk in EMT.

PMID- 19164908
TI  - Screening of DNA aptamer against mouse prion protein by competitive selection.
AB  - Prion disease is a neurodegenerative disorder, in which the normal prion protein
      (PrP) changes structurally into an abnormal form and accumulates in the brain.
      There is a great demand for the development of a viable approach to diagnosis and
      therapy. Not only has the ligand against PrP been used for diagnosis, but it has
      also become a promising tool for therapy, as an antibody. Aptamers are a novel
      type of ligand composed of nucleic acids. DNA aptamers in particular have many
      advantages over antibodies. Therefore, we tried to isolate the DNA aptamer for
      mouse PrP. We developed a competitive selection method and tried to screen the
      DNA aptamer with it. In the fourth round of selection, several clones of the
      aptamer with an affinity to PrP were enriched, and clone 4-9 showed the highest
      affinity of all. The investigation by aptamer blotting and Western blotting
      showed that clone 4-9 was specifically able to recognize both alpha-PrP and beta
      PrP. Moreover, it was indicated that clone 4-9 could recognize the flexible
      region of the N-terminal domain of PrP. These characteristics suggest that clone
      4-9 might be a useful tool in prion-disease diagnosis and research.

PMID- 19164909
TI  - Effects of mutations in yeast prion [PSI+] on amyloid toxicity manifested in
      Escherichia coli strain BL21.
AB  - We previously showed that over production of a fusion protein in which the prion
      domain of Saccharomyces cerevisiae [PSI(+)] is connected to glutathione S
      transferase (GST-Sup35NM) causes a marked decrease in the colony forming ability
      of Escherichia coli strain BL21 after reaching stationary phase. Evidence
      indicated that the observed toxicity was attributable to intracellular formation
      of fibrous aggregates of GST-Sup35NM. In this report, we describe the isolation
      of plasmids that encode mutant forms of GST-Sup35NM which do not confer the
      toxicity to E. coli strain BL21. Each of the four spontaneous mutant-forms of GST
      Sup35NM obtained revealed amino acid substitutions. One substitution was located
      in the N domain, and the others in the M domain. Congo red binding assay
      indicated that none of these mutant proteins underwent conformational alteration
      in vitro. From these results, we conclude that the M domain, in collaboration
      with the N domain, plays an essential role in aggregation of Sup35NM. In
      addition, our data demonstrate the usefulness of the E. coli expression system in
      studying aggregate-forming proteins.

PMID- 19164910
TI  - Interplays between covalent modifications in the endoplasmic reticulum increase
      conformational diversity in nascent prion protein.
AB  - Prion protein (PrP), the causative agent of transmissible spongiform
      encephalopathies, is synthesized in the endoplasmic reticulum (ER) where it
      undergoes numerous covalent modifications. Here we investigate the
      interdependence and regulation of PrP oxidative folding, N-glycosylation and GPI
      addition in diverse ER conditions. Our results show that formation of the single
      disulphide bond is a pivotal event, essential for PrP transport, and can occur
      post-translationally. Retarding its formation enhances N-glycosylation and GPI
      anchoring. In contrast, lowering ER Ca(2+) concentration inhibits N-glycosylation
      and GPI-anchoring. These data reveal tight interplays between the different ER
      covalent modifications, which collectively increase of PrP conformational
      diversity and may be important for its propagation.

PMID- 19164911
TI  - A structural overview of the vertebrate prion proteins.
AB  - Among the diseases caused by protein misfolding is the family associated with the
      prion protein (PrP). This is a small extracellular membrane-anchored molecule of
      yet unknown function. Understanding how PrP folds both into its cellular and
      pathological forms is thought to be crucial for explaining protein misfolding in
      general and the specific role of PrP in disease. Since the first structure
      determination, an increasing number of structural studies of PrP have become
      available, showing that the protein is formed by a flexible N-terminal region and
      a highly conserved globular C-terminal domain. We review here the current
      knowledge on PrP structure. We focus on vertebrate PrPs and analyse in detail the
      similarities and the differences among the coordinates of the C-terminal domain
      of PrP from different species, in search for understanding the mechanism of
      disease-causing mutations and the molecular bases of species barrier.

PMID- 19164912
TI  - Hacking the code of amyloid formation: the amyloid stretch hypothesis.
AB  - Many research efforts in the last years have been directed towards understanding
      the factors determining protein misfolding and amyloid formation. Protein
      stability and amino acid composition have been identified as the two major
      factors in vitro. The research of our group has been focused on understanding the
      relationship between amino acid sequence and amyloid formation. Our approach has
      been the design of simple model systems that reproduce the biophysical properties
      of natural amyloids. An amyloid sequence pattern was extracted that can be used
      to detect amyloidogenic hexapeptide stretches in proteins. We have added evidence
      supporting that these amyloidogenic stretches can trigger amyloid formation by
      nonamyloidogenic proteins. Some experimental results in other amyloid proteins
      will be analyzed under the conclusions obtained in these studies. Our conclusions
      together with evidences from other groups suggest that amyloid formation is the
      result of the interplay between a decrease of protein stability, and the presence
      of highly amyloidogenic regions in proteins. As many of these results have been
      obtained in vitro, the challenge for the next years will be to demonstrate their
      validity in in vivo systems.

PMID- 19164913
TI  - Protein aggregation and polyasparagine-mediated cellular toxicity in
      Saccharomyces cerevisiae.
AB  - It is well established that protein aggregation is associated with many
      neurodegenerative disorders including polyglutamine diseases, but a mechanistic
      understanding of the role of protein aggregates in the disease pathogenesis
      remains elusive. Previously thought to be the cause of cellular toxicity such as
      cellular dysfunction and cell death, protein aggregation is now proposed to serve
      a protective role by sequestering toxic oligomers from interfering with essential
      physiological processes. To investigate the relationship between protein
      aggregation and cellular toxicity, we have characterized and compared the effects
      of two GFP-fusion proteins that form aggregates in Saccharomyces cerevisiae, one
      with a polyasparagine repeat (GFP(N104)) and one without (GFP(C)). Although both
      proteins can form microscopically visible GFP-positive aggregates, only the
      GFP(N104)-containing aggregates exhibit morphological and biochemical
      characteristics that resemble the aggregates formed by mutant huntingtin in yeast
      cells. Formation of both the GFP(C) and GFP(N104) aggregates depends on
      microtubules, while only the GFP(N104) aggregate requires the chaperone Hsp104
      and the prion Rnq1 and is resistant to SDS. Although no microscopically visible
      GFP(N104) aggregates were observed in the hsp104Delta and rnq1Delta mutant cells,
      SDS-insoluble aggregates can still be detected by the filter trap assay. These
      observations argue that the GFP(N104)-containing aggregates can exist in at least
      two distinct states in vivo. We also show that a nucleus-targeted GFP(N104)
      interferes with transcription from two SAGA-dependant promoters and results in a
      decrease in cell viability. Overall, the results imply that the GFP(N104) protein
      behaves similarly to the mutant huntingtin in yeast cells and provides a new
      model for investigating the interplay between protein aggregates and the
      associated phenotypes.

PMID- 19164914
TI  - Prion propagation: the role of protein dynamics.
AB  - The transfer of phenotypes from one individual to another is a fundamental aspect
      of biology. In addition to traditional nucleic acid-based genetic determinants,
      unique proteins known as prions can also act as elements of inheritance,
      infectivity, and disease. Nucleic acids and proteins encode genetic information
      in distinct ways, either in the sequence of bases in DNA or RNA or in the three
      dimensional structure of the polypeptide chain. Given these differences in the
      nature of the genetic repository, the mechanisms underlying the transmission of
      nucleic acid-based and protein-based phenotypes are necessarily distinct. While
      the appearance, persistence and transfer of nucleic acid determinants require the
      synthesis of new polymers, recent studies indicate that prions are propagated
      through dynamic transitions in the structure of existing protein.

PMID- 19164915
TI  - Chaperone effects on prion and nonprion aggregates.
AB  - Exposure to high temperature or other stresses induces a synthesis of heat shock
      proteins. Many of these proteins are molecular chaperones, and some of them help
      cells to cope with heat-induced denaturation and aggregation of other proteins.
      In the last decade, chaperones have received increased attention in connection
      with their role in maintenance and propagation of the Saccharomyces cerevisiae
      prions, infectious or heritable agents transmitted at the protein level. Recent
      data suggest that functioning of the chaperones in reactivation of heat-damaged
      proteins and in propagation of prions is based on the same molecular mechanisms
      but may lead to different consequences depending on the type of aggregate. In
      both cases the concerted and balanced action of "chaperones' team," including
      Hsp104, Hsp70, Hsp40 and possibly other proteins, determines whether a misfolded
      protein is to be incorporated into an aggregate, rescued to the native state or
      targeted for degradation.

PMID- 19164916
TI  - A short history of small s: a prion of the fungus Podospora anserina.
AB  - Prions are infectious proteins. In fungi, prions correspond to non-Mendelian
      genetic elements whose mode of inheritance has long eluded explanation. The [Het
      s] cytoplasmic genetic element of the filamentous fungus Podospora anserina, was
      originally identified in 1952 and recognized as a prion nearly half a century
      later. The present chapter will attempt to describe the work on [Het-s] from a
      historical perspective. The initial characterization and early genetic and
      physiological studies of [Het-s] are described together with the isolation of the
      [Het-s] encoding gene. More recent work that led to the construction of a
      structural model for this prion is also discussed.

PMID- 19164917
TI  - Ceruloplasmin fragmentation is implicated in 'free' copper deregulation of
      Alzheimer's disease.
AB  - A dysfunction in copper homeostasis seems to occur in Alzheimer's disease (AD).
      We recently demonstrated that an excess of non-ceruloplasmin-copper (i.e., 'free'
      copper) correlates with the main functional and anatomical deficits as well as
      the cerebrospinal markers of the disease, thus suggesting that copper contributes
      to AD neurodegeneration. Aim of this study was to investigate the profile of
      serum ceruloplasmin isoforms immunoreactive protein in relation to copper
      dysfunction in AD. Twenty-five AD patients and 25 controls were included in the
      study. All subjects underwent individual measurements of serum ceruloplasmin and
      copper concentrations, and the amount of 'free' copper was computed for each
      copper and ceruloplasmin pair. Serum samples were also pooled and analyzed by two
      dimensional polyacrylamide gel electrophoresis (2-D PAGE) and western blot
      analysis. The mean concentration of 'free' copper resulted higher in AD patients
      than in controls. Ceruloplasmin 2-D PAGE western blot analysis of pooled sera
      showed in the AD samples low-molecular-weight spots in the <50 kDa range that
      were not detected in controls' pooled sera (p < 0.029). Our data indicate a
      ceruloplasmin fragmentation in the serum of AD patients, possibly related to
      'free' copper deregulation in this disease.

PMID- 19164918
TI  - The prion protein knockout mouse: a phenotype under challenge.
AB  - The key pathogenic event in prion disease involves misfolding and aggregation of
      the cellular prion protein (PrP). Beyond this fundamental observation, the
      mechanism by which PrP misfolding in neurons leads to injury and death remains
      enigmatic. Prion toxicity may come about by perverting the normal function of
      PrP. If so, understanding the normal function of PrP may help to elucidate the
      molecular mechansim of prion disease. Ablation of the Prnp gene, which encodes
      PrP, was instrumental for determining that the continuous production of PrP is
      essential for replicating prion infectivity. Since the structure of PrP has not
      provided any hints to its possible function, and there is no obvious phenotype in
      PrP KO mice, studies of PrP function have often relied on intuition and
      serendipity. Here, we enumerate the multitude of phenotypes described in PrP
      deficient mice, many of which manifest themselves only upon physiological
      challenge. We discuss the pleiotropic phenotypes of PrP deficient mice in
      relation to the possible normal function of PrP. The critical question remains
      open: which of these phenotypes are primary effects of PrP deletion and what do
      they tell us about the function of PrP?

PMID- 19164920
TI  - A systematic evaluation of the function of the protein-remodeling factor Hsp104
      in [PSI+] prion propagation in S. cerevisiae by comprehensive chromosomal
      mutations.
AB  - The yeast prion [PSI(+)] represents an aggregated state of the translational
      release factor Sup35 (eRF3) and deprives termination complexes of functional
      Sup35, resulting in nonsense codon suppression. Protein-remodeling factor Hsp104
      is involved in thermotolerance and [PSI(+)] propagation, however the structure
      and-function relationship of Hsp104 for [PSI(+)] remains unclear. In this study,
      we engineered 58 chromosomal hsp104 mutants that affect residues considered
      structurally or functionally relevant to Hsp104 remodeling activity, yet most
      remain to be examined for their significance to [PSI(+)] in the same genetic
      background. Many of these hsp104 mutants were affected both in thermotolerance
      and [PSI(+)] propagation. However, nine mutants were impaired exclusively for
      [PSI(+)], while two mutants were impaired exclusively for thermotolerance.
      Mutations exclusively affecting [PSI(+)] are clustered around the lateral channel
      of the Hsp104 hexamer. These findings suggest that Hsp104 possesses shared as
      well as distinct remodeling activities for stress-induced protein aggregates and
      [PSI(+)] prion aggregates and that the lateral channel plays a role specific to
      [PSI(+)] prion propagation.

PMID- 19164919
TI  - Prion pathogenesis is independent of caspase-12.
AB  - The pathogenic mechanism(s) underlying neurodegenerative diseases associated with
      protein misfolding is unclear. Several studies have implicated ER stress pathways
      in neurodegenerative conditions, including prion disease, amyotrophic lateral
      sclerosis, Alzheimer's disease and many others. The ER stress response and
      upregulation of ER stress-responsive chaperones is observed in the brains of
      patients affected with Creutzfeldt-Jacob disease and in mouse models of prion
      diseases. In particular, the processing of caspase-12, an ER-localized caspase,
      correlates with neuronal cell death in prion disease. However, the contribution
      of caspase-12 to neurodegeneration has not been directly addressed in vivo. We
      confirm that ER stress is induced and that caspase-12 is proteolytically
      processed in a murine model of infectious prion disease. To address the causality
      of caspase-12 in mediating infectious prion pathogenesis, we inoculated mice
      deficient in caspase-12 with prions. The survival, behavior, pathology and
      accumulation of proteinase K-resistant PrP are indistinguishable between caspase
      12 knockout and control mice, suggesting that caspase-12 is not necessary for
      mediating the neurotoxic effects of prion protein misfolding.

PMID- 19164921
TI  - Spatial signaling networks converge at the adaptor protein Shc.
AB  - Endothelial cells, which are located at the interface between the blood and the
      vessel wall, respond dynamically to a variety of stimuli initiating signaling
      cascades that regulate cardiovascular development, physiology and pathology.
      These inputs include soluble factors that bind to their receptors, integrin
      matrix interactions, cell-cell contacts and mechanical forces due to the flowing
      blood. While these stimuli can mediate unique downstream signals, it is well
      accepted that signaling pathways are highly interwoven into complex signaling
      networks with several levels of cross-talk, integration and coordination. Recent
      studies suggest that several signaling networks coalesce at the adaptor protein
      Shc.

PMID- 19164922
TI  - Pro-apoptotic effect of aurothiomalate in prostate cancer cells.
AB  - It has been recently demonstrated that small gold compounds could have a
      potential anti-tumoral activity. Here, we report that aurothiomalate (ATM), a
      gold compound already used in clinical therapy for the treatment of rheumatoid
      arthritis, has a pro-apoptotic effect in aggressive prostate cancer (PC3U) cells.
      In contrast, treatment of human primary epithelial prostate cells (PrEC) with ATM
      did not cause apoptosis. We demonstrated that ATM is able to disrupt the PKCiota
      Par6 complex in PC3U cells and that this disruption leads to the activation of
      ERK in a dose-dependent manner. Interestingly, we also showed that ERK acts
      upstream of the activation of caspase 3, leading to apoptosis. ATM treatment also
      causes activation of p38 and JNK MAP kinases. Moreover we could link ATM
      treatment to activation of the mitochondrial or so called intrinsic pathway, as
      we observed release of cytochrome c from mitochondria to cytoplasm, suggesting
      that the mitochondrial pathway is involved in the pro-apoptotic effect mediated
      by ATM. Taken together our data suggest that ATM could be a new promising drug
      for the treatment of advanced prostate cancer.

PMID- 19164923
TI  - Antiprion drugs as chemical tools to uncover mechanisms of prion propagation.
AB  - A number of drugs active against prions either in vitro, in cellular systems or
      in vivo in animal models have been isolated in various screening assays. In this
      minireview, we would like to suggest, that in addition to their direct interest
      as potential therapeutic agents, these molecules could be used as original
      research tools to understand prion propagation. The use of antiprion compounds as
      tool to understand fundamentals of prion propagation relies on reverse screening
      approaches. These global genetic and/or biochemical approaches aim to identify
      the intracellular target(s) and mechanism of action of the drugs. Once those are
      known, the biological activity of the compounds can be optimized on a rational
      basis, their potential side effects understood and minimized. In vitro enzyme
      based screening assays can then be designed to allow discovery of new, more
      potent and selective molecules. Here we describe the main comprehensive
      biochemical and genetical approaches to realize reverse screening approaches
      based on antiprion drugs. We will finish by discussing the interest of using drug
      inactivation of specific targets as a substitute to genetic inactivation.

PMID- 19164925
TI  - Protein misfolding and aggregation in ageing and disease: molecular processes and
      therapeutic perspectives.
AB  - Although intensively researched, the fundamental mechanism of protein misfolding
      that leads to protein aggregation and associated diseases remains somewhat
      enigmatic. The failure of a protein to correctly fold de novo or to remain
      correctly folded can have profound consequences on a living system especially
      when the cellular quality control processes fail to eliminate the rogue proteins.
      Over 20 different human diseases have now been designated as 'conformational
      diseases' and include neurodegenerative diseases such as Alzheimer's disease
      (AD), Huntington's disease (HD) and Creutzfeldt Jakob disease (CJD) that are
      becoming increasingly prevalent in an ageing human population. Such diseases are
      usually characterised by the deposition of specific misfolded proteins as amyloid
      fibrils and hence are often referred to as the amyloidoses.

PMID- 19164924
TI  - The genetic control of the formation and propagation of the [PSI+] prion of
      yeast.
AB  - It is over 40 years since it was first reported that the yeast Saccahromyces
      cerevisiae contains two unusual cytoplasmic 'genetic' elements: [PSI(+)] and
      [URE3]. Remarkably the underlying determinants are protein-based rather than
      nucleic acid-based, i.e., that they are prions, and we have already learnt much
      about their inheritance and phenotypic effects from the application of
      'classical' genetic studies alongside the more modern molecular, cellular and
      biochemical approaches. Of particular value has been the exploitation of chemical
      mutagens and 'antagonistic' mutants which directly affect the replication and/or
      transmission of yeast prions. In this Chapter we describe what has emerged from
      the application of classical and molecular genetic studies, to the most
      intensively studied of the three native yeast prions, the [PSI(+)] prion.

PMID- 19164926
TI  - Characterization of proteins associated with polyglutamine aggregates: a novel
      approach towards isolation of aggregates from protein conformation disorders.
AB  - The common feature of many neurodegenerative diseases is emergence of protein
      aggregates. Identifying their composition can provide valuable insights into the
      cellular mechanisms of protein aggregation and neuronal death. No reliable method
      for identification of the aggregate-associated proteins has been available. Here
      we describe a method for characterization of protein aggregates based on
      sedimentation of immunocomplexes without involvement of a solid support. As a
      model, we used the aggregates formed in yeast by a polyglutamine-containing
      segment of mutant huntingtin. Sixteen proteins associated with the isolated
      aggregates were identified with 2-D gel electrophoresis followed by mass
      spectrometry. We found that the aggregates in cells lacking Rnq1 prion recruited
      lesser amounts of chaperones than those in the wild-type cells. The method can be
      utilized for characterization of various types of aggregates, prions and very
      large protein complexes under mild conditions that preserve associated proteins.

PMID- 19164927
TI  - Computational simulations of the early steps of protein aggregation.
AB  - There is strong evidence that the oligomers of key proteins, formed during the
      early steps of aggregation, could be the primary toxic species associated with
      human neuro-degenerative diseases, such as Alzheimer's and prion diseases. Here,
      we review recent progress in the development of computational approaches in order
      to understand the structures, dynamics and free energy surfaces of oligomers. We
      also discuss possible research directions for the coming years.

PMID- 19164928
TI  - Yeast prions: evolution of the prion concept.
AB  - Prions (infectious proteins) analogous to the scrapie agent have been identified
      in Saccharomyces cerevisiae and Podospora anserina based on their special genetic
      characteristics. Each is a protein acting as a gene, much like nucleic acids have
      been shown to act as enzymes. The [URE3], [PSI(+)], [PIN(+)] and [Het-s] prions
      are self-propagating amyloids of Ure2p, Sup35p, Rnq1p and the HET-s protein,
      respectively. The [beta] and [C] prions are enzymes whose precursor activation
      requires their own active form. [URE3] and [PSI(+)] are clearly diseases, while
      [Het-s] and [beta] carry out normal cell functions. Surprisingly, the prion
      domains of Ure2p and Sup35p can be randomized without loss of ability to become a
      prion. Thus amino acid content and not sequence determine these prions.
      Shuffleability also suggests amyloids with a parallel in-register beta-sheet
      structure.

PMID- 19164930
TI  - Regulatory mechanism of histone epigenetic modifications in plants.
AB  - Histone H3 lysine 9 and lysine 27 are two important targets for epigenetic
      modifications in plants. H3K9 methylation is either associated with
      heterochromatin formation or gene repression, while H3K27 methylation profile is
      likely to be involved in gene expression required for developmental decisions.
      Although a number of modification enzymes are being identified, the mode of
      action and functional interplay between the histone modification enzymes and
      other chromatin pathways remain largely unknown. Studying the regulatory
      mechanism of histone H3K9 and H3K27 modification would provide important clues to
      reveal the molecular basis of establishment, inheritance and erasure of
      epigenetic information during plant cell division and differentiation.

PMID- 19164929
TI  - Centriole inheritance.
AB  - Early cell biologists perceived centrosomes to be permanent cellular structures.
      Centrosomes were observed to reproduce once each cycle and to orchestrate
      assembly a transient mitotic apparatus that segregated chromosomes and a
      centrosome to each daughter at the completion of cell division. Centrosomes are
      composed of a pair of centrioles buried in a complex pericentriolar matrix. The
      bulk of microtubules in cells lie with one end buried in the pericentriolar
      matrix and the other extending outward into the cytoplasm. Centrioles recruit and
      organize pericentriolar material. As a result, centrioles dominate microtubule
      organization and spindle assembly in cells born with centrosomes. Centrioles
      duplicate in concert with chromosomes during the cell cycle. At the onset of
      mitosis, sibling centrosomes separate and establish a bipolar spindle that
      partitions a set of chromosomes and a centrosome to each daughter cell at the
      completion of mitosis and cell division. Centriole inheritance has historically
      been ascribed to a template mechanism in which the parental centriole contributed
      to, if not directed, assembly of a single new centriole once each cell cycle. It
      is now clear that neither centrioles nor centrosomes are essential to cell
      proliferation. This review examines the recent literature on inheritance of
      centrioles in animal cells.

PMID- 19164931
TI  - Anti-LRP/LR antibody W3 hampers peripheral PrPSc propagation in scrapie infected
      mice.
AB  - We identified the 37kDa/67kDa laminin receptor (LRP/LR) as a cell surface
      receptor for the cellular prion protein (PrP(c)) and the infectious prion protein
      (PrP(Sc)). Recently, we showed that anti-LRP/LR antibody W3 cured scrapie
      infected N2a cells. Here, we demonstrate that W3 delivered by passive
      immunotransfer into C57BL/6 mice reduced the PrP(Sc) content in the spleen
      significantly by 66%, demonstrating an impairment of the peripheral PrP(Sc)
      propagation. In addition, we observed a 1.8-fold increase in survival of anti
      LRP/LR antibody W3 treated mice (mean survival of 31 days) compared to preimmune
      serum treated control animals (mean survival of 17 days). We conclude that the
      significant effect of anti-LRP/LR antibody W3 on the reduction of peripheral
      PrP(Sc) propagation might be due to the blockage of the prion receptor LRP/LR
      which is required, as previously shown in vitro, for PrP(Sc) propagation in vivo.

PMID- 19164933
TI  - Radiation-induced apoptosis is modulated by the post-irradiation tumor
      microenvironment.
AB  - The sensitivity of cells to radiation-induced apoptosis is considered to be low
      in solid tumors. This is thought to arise largely from inherent resistance caused
      by apoptotic pathway mutations. However, other factors may contribute to
      apoptotic resistance. Poor vasculature and abnormal tumor metabolism lead to a
      tumor microenvironment characterized by conditions of hypoxia, low glucose and
      extracellular acidosis. Hypoxia during irradiation is well known to cause
      resistance and is a barrier to successful treatment. We hypothesized that post
      irradiation microenvironmental conditions can modulate radiation-induced
      apoptosis and that this may in part contribute to therapeutic resistance. In
      order to test this, radiation-induced apoptosis was assessed in U937 cells in
      suspension and in a novel multicellular agarose-diffusion-system. Post
      irradiation hypoxia failed to modify the extent of apoptosis in suspension cells,
      suggesting that post-irradiation hypoxia may be of little consequence to
      apoptosis induction in this model. In contrast, low glucose post-irradiation
      significantly inhibited radiation-induced apoptosis. While short (five hours)
      exposure to acidosis also appeared to inhibit radiation-induced apoptosis, the
      lack of modulation after extended (20 hours) exposure suggests that acidosis may
      only delay apoptosis. In the more complex agarose diffusion-limitation model,
      radiation-induced apoptotic sensitivity was found to be reduced in cells distant
      from the diffusion edge representing poorly perfused tumor cells in vivo.
      Overall, the results suggest that the post-irradiation tumor microenvironment may
      affect radiation-induced apoptosis and thus may influence therapeutic response.
      Therefore, the post-irradiation tumor microenvironment may be a target for
      therapeutic intervention.

PMID- 19164932
TI  - Primary tumor cells obtained from MNU-induced mammary carcinomas show immune
      heterogeneity which can be modulated by low-efficiency transfection of CD40L
      gene.
AB  - The presence of CD40 on carcinoma cells is an important factor for the generation
      of tumor-specific responses induced by CD40 ligation. In an N-methyl-N
      nitrosourea (MNU)-induced autochthonous mammary tumor model, we analyzed the
      immune features of primary tumor cells. Here, CD40 was frequently detected on the
      primary tumor cultures and selectively expressed on the malignant mammary tissue
      in vivo. On the other hand, every mammary tumor cell culture had a heterogeneous
      and reduced expression of proinflammatory TNFalpha, IL-1beta, IL-6 and CXCL1
      cytokines compared to normal mammary epithelial cells. Low-efficiency
      transfection of CD40 ligand (CD40L) gene enhanced the expression of
      proinflammatory cytokines in the tumor cells and strengthened allogeneic immune
      reactions and costimulatory activity which may help overwhelming suppressive
      features of the tumor.

PMID- 19164934
TI  - Autophagy meets planarians.
AB  - This review aims to demonstrate the importance of freshwater planarians as model
      organisms, particularly emphasizing those characteristics of the animal that make
      them a good model to study autophagy. The aim of this review is to provide a
      better understanding of autophagy in this model for the nonplanarian reader, and
      elucidate the relevance of autophagy research in this peculiar model organism.
      Furthermore, I will try to synthesize the evidence showing the importance of
      autophagy in planarian body remodeling, and I will discuss some ideas about the
      role of autophagy in stem cell biology. In light of these new developments, it is
      likely that the planarian field will make an important contribution to the study
      of the molecular mechanisms involved in autophagy in the future.

PMID- 19164935
TI  - BCG vaccines: their mechanisms of attenuation and impact on safety and protective
      efficacy.
AB  - Mycobacterium bovis Bacille Calmette-Guerin (BCG) was developed as an attenuated
      live vaccine for tuberculosis control nearly a century ago. Despite being the
      most widely used vaccine in human history, the mechanisms of attenuation of BCG
      remain poorly understood. BCG is not a single organism, but comprises a number of
      substrains that differ in genotypes and phenotypes. The impacts of these
      differences on BCG vaccine properties are largely unknown. Nevertheless, in the
      past decade, the development of sophisticated genome analysis techniques, coupled
      with advances in knowledge of the virulence mechanisms of Mycobacterium
      tuberculosis, have provided greater insights into the attenuation and evolution
      of BCG. This review article discusses these new developments, focusing on
      molecular mechanisms that contribute to the attenuation of BCG substrains. It is
      evident that BCG strains comprise natural mutants of major virulence factors of
      M. tb, including ESX-1, PDIM/PGL and PhoP, and that BCG substrains differ
      markedly in virulence level. The impacts of these findings on vaccine properties
      including adverse reaction effect, tuberculin reactivity and protective efficacy
      are discussed. These new insights have extremely important implications for
      national immunization programs and the development of future vaccines.

PMID- 19164936
TI  - Flies as the ointment: Drosophila modeling to enhance drug discovery.
AB  - Development of a drug and its safe therapeutic application necessitates using
      animal models for testing purposes. While testing with mammalian models is
      essential prior to approval for human trials, the use of invertebrate animal
      models that are amenable to molecular genetic manipulations provide experimental
      and biological advantages that can streamline the discovery and testing process.
      Among the benefits of a genetics-based approach is the ability to screen for
      genes/proteins that may be novel drug targets, and the expedited development of
      genetic backgrounds that more accurately reflect a specific disease state. An
      invertebrate model may provide a more robust phenotype for screening, a situation
      that may arise when there is unanticipated genetic redundancy present in the
      mammalian model. Finally, the comparatively short generation time and fecundity
      of invertebrate models allows for increased experimental throughput. Together,
      these factors may contribute towards savings in time and cost during the drug
      discovery process.

PMID- 19164938
TI  - Thiazolidinediones regulate expression of cell cycle proteins in human prostate
      cancer cells via PPARgamma-dependent and PPARgamma-independent pathways.
AB  - Thiazolidinediones (TZDs) are peroxisome proliferator activated receptor gamma
      (PPARgamma) ligands that have been reported to reduce proliferation of human
      prostate cancer cells. However, the mechanisms by which TZDs inhibit prostate
      cancer cell proliferation are not fully understood. In addition, it is not known
      if the anti-proliferative effects of TZDs require activation of PPARgamma or are
      mediated by PPARgamma-independent pathways. The goals of this study were to
      assess whether TZDs regulate expression of proteins that control the transition
      from G1 to S phase of the cell cycle and define the role of PPARgamma in these
      TZD-induced responses in androgen-independent human prostate cancer cell lines.
      Western blot analysis revealed that growth inhibitory concentrations of the TZDs
      rosiglitazone and ciglitazone induced expression of the cyclin dependent kinase
      inhibitor p21 and decreased cyclin D1 levels in the androgen independent PC-3
      cell line. Phosphorylation of retinoblastoma protein at Serine 780 was also
      reduced in PC-3 cells exposed to ciglitazone. Furthermore, growth inhibitory
      concentrations of ciglitazone increased p21 and lowered cyclin D1 expression
      within C4-2 cells. PPARgamma-directed siRNAs inhibited the ability of
      rosiglitazone to regulate expression of cyclin D1 and p21. However, knockdown of
      PPARgamma did not significantly reduce ciglitazone-induced alterations in cyclin
      D1 and p21. Furthermore PPARgamma siRNA did not prevent inhibition of PC-3 cell
      proliferation by either TZD. Thus, activation of PPARgamma is involved in
      rosiglitazone-induced alterations in cell cycle protein expression. However, the
      alterations in protein expression and proliferation induced by ciglitazone occur
      primarily via PPARgamma-independent signaling pathways.

PMID- 19164937
TI  - Apoptosis of B-cell chronic lymphocytic leukemia cells induced by a novel BH3
      peptidomimetic.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in human
      adults of the Western world and no definitive cure is yet available. The disease
      is characterized by accumulation of clonal malignant B lymphocytes resistant to
      apoptosis. Strategies to hit the anti-apoptotic drift of the Bcl-2 family in B
      CLL cells are being explored. A novel peptidomimetic based on the BH3 domain of
      the pro-apoptotic protein Bim and recently shown to exert significant apoptotic
      activity on acute myeloid leukemia cells, both in vitro and in vivo, was assayed
      on ex-vivo derived leukemic cells from untreated B-CLL patients (n = 7). We found
      that this peptide, named 072RB, induced apoptosis of B-CLL samples at a
      concentration that does not affect viability of peripheral and bone marrow
      derived lymphocytes from healthy donors. Apoptosis was demonstrated by activation
      of Bak and Bax, externalization of plasma membranes phosphadydilserines,
      appearance of hypodiploid events in DNA flow cytometry histograms and was
      accompanied by dissipation of the mitochondrial transmembrane potential. Before
      the onset of marked apoptotic signs a progressive decline of the relevant anti
      apoptotic proteins Bcl-X(L) and Mcl-1 could be observed. The negative control
      peptide 072RBL94A was ineffective for B-CLL cells, supporting the sequence
      specificity of 072RB activity. No relationship was found between responsiveness
      to 072RB and Mcl-1/Bcl-X(L) basal levels or decrease magnitude, possibly because
      of the limited sample size of the study. Altogether, we demonstrate that 072RB
      induces significant apoptosis of B-CLL cells subsequent to Bcl-X(L) and Mcl-1
      downregulation.

PMID- 19164939
TI  - Attitudes to HPV vaccination among ethnic minority mothers in the UK: an
      exploratory qualitative study.
AB  - OBJECTIVE: The objective of this study was to explore attitudes to HPV
      vaccination among black and Asian mothers living in Britain. RESULTS: Five major
      themes emerged from the data: (1) Experience of vaccination, (2) Awareness of HPV
      vaccination and reactions to the information, (3) reasons for giving vaccination,
      (4) concerns about vaccination and (5) social influences. Visits to family abroad
      meant additional experience with vaccinations. There were concerns about how
      vaccine effects could vary by ethnicity as a result of physical differences
      (e.g., sickle-cell anaemia), and mothers wanted to know whether the HPV vaccine
      had been tested fully in their ethnic group. Most mothers struggled to understand
      why their daughter could not have the vaccination when she was older and some
      felt that 12/13 years was too young. Religious beliefs meant that mothers thought
      the vaccine would be less acceptable to other family members or would be
      perceived as unnecessary because of their low risk of HPV. DESIGN: This study
      used qualitative methodology. Face-to-face interviews were carried out with
      Black/Black British (n = 10) and Asian/Asian British mothers (n = 10). Interviews
      lasted approximately 40 minutes, were recorded and transcribed verbatim. Data
      were analyzed using Framework Analysis. CONCLUSION: It is important to include
      ethnic minority parents in psychosocial research surrounding HPV vaccination to
      ensure that culturally specific barriers are identified and targeted, limiting
      ethnic inequalities in cancer risk. Ethnically dense areas of Britain may benefit
      from tailoring HPV information to the local population, reflecting differences in
      cultural beliefs.

PMID- 19164940
TI  - Making metabolic decisions in Drosophila.
AB  - Physiology and behavior have historically been treated as separate subjects in
      the study of Drosophila. The latter is mentioned mainly in the context of
      neurobiology, while the former has been considered to take in studies of
      metabolism, cell biology and anatomy, among others. Of late, the line
      distinguishing physiology and behavior has become thinner, and this is
      exceptionally apparent in recent studies of nutrient signaling and of the
      regulation of feeding. This review represents a brief examination of the nexus
      between these intersecting fields of research in Drosophila. Other recently
      published reviews serve as complements to this one.

PMID- 19164941
TI  - Reuse, replace, recycle. Specificity in subunit inheritance and assembly of
      higher-order septin structures during mitotic and meiotic division in budding
      yeast.
AB  - Septins are guanine nucleotide-binding proteins that form hetero-oligomeric
      complexes, which assemble into filaments and higher-order structures at sites of
      cell division and morphogenesis in eukaryotes. Dynamic changes in the
      organization of septin-containing structures occur concomitantly with progression
      through the mitotic cell cycle and during cell differentiation. Septins also
      undergo stage-specific post-translational modifications, which have been
      implicated in regulating their dynamics, in some cases via purported effects on
      septin turnover. In our recent study, the fate of two of the five septins
      expressed in mitotic cells of budding yeast (Saccharomyces cerevisiae) was
      tracked using two complementary fluorescence-based methods for pulse-chase
      analysis. During mitotic growth, previously-made molecules of both septins (Cdc10
      and Cdc12) persisted through multiple successive divisions and were incorporated
      equivalently with newly synthesized molecules into hetero-oligomers and higher
      order structures. Similarly, in cells undergoing meiosis and the developmental
      program of sporulation, pre-existing copies of Cdc10 were incorporated into new
      structures. In marked contrast, Cdc12 was irreversibly excluded from septin
      complexes and replaced by another septin, Spr3. Here, we discuss the broader
      implications of these results and related findings with regard to how septin
      dynamics is coordinated with the mitotic cell cycle and in the yeast life cycle,
      and how these observations may relate to control of the dynamics of other complex
      multi-subunit assemblies.

PMID- 19164942
TI  - Polo-like kinase 4 phosphorylates Chk2.

PMID- 19164943
TI  - There are many ways to train a fly.
AB  - A biological understanding of memory remains one of the great quests of
      neuroscience. For over 30 years the fruit fly Drosophila melanogaster has
      primarily been viewed as an excellent vehicle to find 'memory genes'. However,
      the recent advent of sophisticated genetic tools to manipulate neural activity
      has meant that these genes can now be viewed within the context of functioning
      neural circuits. A holistic understanding of memory in flies is therefore now a
      realistic goal. Larvae and adult flies exhibit remarkable behavioral complexity
      and they can both be trained in a number of ways. In this review, our intention
      is to summarize the many assays that have been developed to study plastic
      behaviors in flies. More specific and detailed reviews have been published by us
      and others, reviewed in references 1-6. While our bias for olfactory conditioning
      paradigms is obvious, our purpose here is not to pass judgment on each method. We
      would rather leave that to those readers who might be inspired to try each assay
      for themselves.

PMID- 19164944
TI  - Phenotypic approach to drug discovery.

PMID- 19164946
TI  - Replication checkpoint control by a PTK/STAT3/cyclin D1 axis.
AB  - Tyrosine phosphorylation-dependent signalling, controlled by the opposing actions
      of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), is
      typically associated with the cellular response to mitogens in G1. However, a
      growing number of studies indicate that PTKs and PTPs can have important roles in
      cellular division beyond this initial phase of the cell cycle. In this
      Perspective we discuss the impact and contributions of PTKs and PTPs to cell
      cycle checkpoints. We focus on the replication checkpoint and our recent findings
      that demonstrate that the attenuation of PTK-mediated STAT3 signalling for the
      depletion of cyclin D1, works in concert with ATR-instigated cascades for the
      suppression of S-phase progression. We argue for the need for integrated
      responses and highlight the potential for oncogenic PTK pathways to bypass the
      replication checkpoint and contribute to genomic instability.

PMID- 19164945
TI  - Pediatric low-grade gliomas and the need for new options for therapy: Why and
      how?
AB  - Pediatric low-grade gliomas are the most common tumors of the central nervous
      system in children, accounting for almost 50% of all childhood brain tumors. They
      are a heterogeneous group of tumors with different histologic subtypes. Most
      treatment studies address low-grade gliomas as a single entity, depriving us of
      histology-specific treatment outcomes. This is mostly due to a lack of
      understanding of tumor biology at the molecular level. Pediatric low-grade
      gliomas are not benign, and most incompletely resected tumors will progress and
      negatively affect quality of life. The advancements made in understanding
      sporadic pilocytic astrocytoma and neurofibromatosis 1-associated pilocytic
      astrocytoma in particular have paved the way for potential targeted therapy and
      biological stratification. Such progress in pilocytic astrocytoma needs to be
      consolidated and expanded to other histologic varieties of pediatric low-grade
      gliomas.

PMID- 19164947
TI  - Regulation and function of the melanization reaction in Drosophila.
AB  - The melanization reaction, involving the synthesis of melanin to encapsulate
      pathogens, is a prominent immune response in Drosophila, the mosquito and other
      insects and arthropods. Biochemical studies with large insects have defined a
      basic model for how melanization is activated and regulated upon microbial
      infection. In this model, recognition of a microorganism triggers a serine
      protease cascade that activates phenol oxidase (PO), a key enzyme in the melanin
      biosynthetic pathway, and serpin-type protease inhibitors are involved in
      inhibiting the cascade. In the past few years, genetic studies in Drosophila have
      identified serine proteases and serpins that regulate activation of PO and
      melanization in vivo. These studies, along with molecular genetic analysis of
      melanization in the mosquito, have provided new insight into the role that
      melanization plays in fighting microbial infection.

PMID- 19164948
TI  - Effect of Helicobacter pylori's vacuolating cytotoxin on the autophagy pathway in
      gastric epithelial cells.
AB  - Host cell responses to Helicobacter pylori infection are complex and incompletely
      understood. Here, we report that autophagy is induced within human-derived
      gastric epithelial cells (AGS) in response to H. pylori infection. These
      autophagosomes were distinct and different from the large vacuoles induced during
      H. pylori infection. Autophagosomes were detected by transmission electron
      microscopy, conversion of LC3-I to LC3-II, GFP-LC3 recruitment to autophagosomes,
      and depended on Atg5 and Atg12. The induction of autophagy depended on the
      vacuolating cytotoxin (VacA) and, moreover, VacA was sufficient to induce
      autophagosome formation. The channel-forming activity of VacA was necessary for
      inducing autophagy. Intracellular VacA partially co-localized with GFP-LC3,
      indicating that the toxin associates with autophagosomes. The inhibition of
      autophagy increased the stability of intracellular VacA, which in turn resulted
      in enhanced toxin-mediated cellular vacuolation. These findings suggest that the
      induction of autophagy by VacA may represent a host mechanism to limit toxin
      induced cellular damage.

PMID- 19164949
TI  - Hippo signaling pathway and organ size control.
AB  - Initially discovered in Drosophila, the Hippo (Hpo) pathway has been recognized
      as a conserved signaling pathway that controls organ size during development by
      restricting cell growth and proliferation and by promoting apoptosis. In
      addition, abnormal activities of several Hpo pathway components have been
      implicated in human cancer. Here, we review the current understanding of the
      molecular and cellular basis of Hpo signaling in development and tumorigenesis,
      and discuss how the Hpo pathway integrates spatial and temporal signals to
      control tissue growth and organ size.

PMID- 19164950
TI  - Radiation-induced autophagy in normal and cancer cells: towards novel
      cytoprotection and radio-sensitization policies?
AB  - Autophagy or Type II programmed cell death (PCD) is a major intracellular pathway
      for the degradation and recycling of proteins, ribosomes and entire organelles.
      The role of this pathway in the antitumor effect of radiotherapy and in radiation
      toxicity is obscure. A complicated machinery of genes and proteins is involved in
      the regulation of autophagy as a response to a variety of stress factors
      including hypoxia, nutrient deprivation, cytotoxic agents and radiotherapy.
      Continuously accumulating data suggest that autophagic response of cancer cells
      to radiotherapy is a major pathway which, in contrast to apoptosis that leads to
      death, may lead to either death or cellular survival. A variety of agents have
      been recognized that induce or block autophagy, directly interfering with the
      cytotoxic effect of radiotherapy. Simultaneous targeting of autophagy and
      apoptosis during radiotherapy seems to further augment the antitumor effect.
      Radiobiology research should focus on the differential effect of fractionation on
      the induction of autophagy in different tumors and on the manipulation of this
      with autophagy triggering agents. Whether manipulation of this pathway in normal
      tissues may be used to confer cytoprotection also deserves thorough
      investigation. Moreover, the role of pretreatment autophagic indices in tumor
      cells in predicting radiotherapy and chemotherapy outcome should be examined in
      translational studies.

PMID- 19164951
TI  - Inhibiting PI-3-K for glioma therapy.

PMID- 19164952
TI  - Do checkpoint kinases contribute to HIV-1-mediated apoptosis?

PMID- 19164953
TI  - Plk1, a negative regulator of p21?

PMID- 19164954
TI  - Checkpoint "madness".

PMID- 19164956
TI  - Waterton riding the cayman.

PMID- 19164957
TI  - Ettmuller's classic on intravenous therapy.

PMID- 19164958
TI  - Increased volatile anesthetic requirement in short-sleeping Drosophila mutants.
AB  - BACKGROUND: Anesthesia and sleep share physiologic and behavioral similarities.
      The anesthetic requirement of the recently identified Drosophila mutant
      minisleeper and other Drosophila mutants was investigated. METHODS: Sleep and
      wakefulness were determined by measuring activity of individual wild-type and
      mutant flies. Based on the response of the flies at different concentrations of
      the volatile anesthetics isoflurane and sevoflurane, concentration-response
      curves were generated and EC50 values were calculated. RESULTS: The average
      amount of daily sleep in wild-type Drosophila (n = 64) was 965 +/- 15 min, and
      1,022 +/- 29 in Na[har](P > 0.05; n = 32) (mean +/- SEM, all P compared to wild
      type and other shaker alleles). Sh flies slept 584 +/- 13 min (n = 64, P < 0.01),
      Sh flies 412 +/- 22 min (n = 32, P < 0.01), and Sh flies 782 +/- 25 min (n = 32,
      P < 0.01). The EC50 values for isoflurane were 0.706 (95% CI 0.649 to 0.764, n =
      661) and for sevoflurane 1.298 (1.180 to 1.416, n = 522) in wild-type Drosophila;
      1.599 (1.527 to 1.671, n = 308) and 2.329 (2.177 to 2.482, n = 282) in Sh, 1.306
      (1.212 to 1.400, n = 393) and 2.013 (1.868 to 2.158, n = 550) in Sh, 0.957 (0.860
      to 1.054, n = 297) and 1.619 (1.508 to 1.731, n = 386) in Sh, and 0.6154 (0.581
      to 0.649, n = 360; P < 0.05) and 0.9339 (0.823 to 1.041, n = 274) in Na[har],
      respectively (all P < 0.01). CONCLUSIONS: A single-gene mutation in Drosophila
      that causes an extreme reduction in daily sleep is responsible for a significant
      increase in the requirement of volatile anesthetics. This suggests that a single
      gene mutation affects both sleep behavior and anesthesia and sedation.

PMID- 19164959
TI  - Early packed red blood cell transfusion and acute respiratory distress syndrome
      after trauma.
AB  - BACKGROUND: Transfusion of packed red blood cells (PRBCs) is a risk factor for
      acute respiratory distress syndrome (ARDS) in trauma patients. Yet, there is a
      paucity of information regarding the risk of ARDS with incremental PRBCs
      exposure. METHODS: For this retrospective analysis, eligible patients from
      National Study on Costs and Outcomes of Trauma were included. Our main exposure
      was defined as units of PRBCs transfused during the first 24 h after admission.
      The main outcome was ARDS. RESULTS: A total of 521 (4.6%) of 14070 patients
      developed ARDS, and 331 patients (63.5%) who developed ARDS received PRBCs
      transfusion. Injury severity, thoracic injury, polytrauma, and pneumonia
      receiving more than 5 units of fresh frozen plasma and 6-10 units of PRBCs were
      independent predictors of ARDS. Patients receiving more than 5 units of PRBCs had
      higher risk of developing ARDS (patients who received 6-10 units: adjusted odds
      ratio 2.5, 95% CI 1.12-5.3; patients who received more than 10 units: odds ratio
      2.6, 95% CI 1.1-6.4). Each additional unit of PRBCs transfused conferred a 6%
      higher risk of ARDS (adjusted odds ratio 1.06; 95% CI 1.03-1.10). CONCLUSIONS:
      Early transfusion of PRBCs is an independent predictor of ARDS in adult trauma
      patients. Conservative transfusion strategies that decrease PRBC exposure by even
      1 unit may be warranted to reduce the risk of ARDS in injured patients.

PMID- 19164960
TI  - Robinson improved induction coil and battery for chloroform overdose.

PMID- 19164961
TI  - Beta-eucaine bottle.

PMID- 19164964
TI  - Residual confounding in observational studies.

PMID- 19164965
TI  - Difficult tracheal intubation and a low hyoid.

PMID- 19164967
TI  - Nasal ventilation is more effective than combined oral-nasal ventilation during
      induction of general anesthesia in adult subjects.

PMID- 19164968
TI  - Appropriate endotracheal tube placement in children: don't throw away your
      stethoscopes yet!

PMID- 19164971
TI  - Innovative thinking in the care of cardiac surgical patients.

PMID- 19164972
TI  - Increasing operating room throughput via parallel processing may not require
      extra resources.

PMID- 19164975
TI  - Getting clefts to the forefront of plastic surgery, based on new innovation and
      advances: the crusaders of the lost ark.

PMID- 19164976
TI  - In memory of Paul Tessier, MD (1917-2008).

PMID- 19164977
TI  - Bone tissue engineering, the new concept in regenerative medicine and surgery:
      reflections on innovations.

PMID- 19164979
TI  - Tough and tactical tackling of terror.

PMID- 19164978
TI  - Innovations in the management of facial trauma.

PMID- 19164980
TI  - Posttraumatic facial restoration: a philosophy of care.
AB  - Posttraumatic facial restoration requires the marriage of both aesthetic and
      reconstructive principles. An outline for the treatment of traumatic facial
      injuries is presented.

PMID- 19164981
TI  - Soccer-related facial fractures: postoperative management with facial protective
      shields.
AB  - Facial fractures are one of the most common orofacial injury sustained during
      participation in sporting events.The frequency of maxillofacial lesions varies
      according to the popularity that each sport has in a particular country. Soccer
      is the most popular sport in Italy, and it is responsible for a large number of
      facial traumas.Traumas and fractures in soccer mainly involve the zygomatic and
      nasal regions and are especially caused by direct contact that takes place mainly
      when the ball is played with the forehead. In particular, elbow-head and head
      head impacts are the most frequent dangerous contacts.Soccer is not a violent
      sport, and the use of protective helmets is not allowed because it could be
      dangerous especially when players play the ball with the head. The use of
      protective facial shields are exclusively permitted to preserve players who
      underwent surgery for facial fractures.The use of a facial protection mask after
      a facial fracture treatment has already been reported. This article describes a
      clinical experience of management of 4 soccer-related facial fractures by means
      of fabrication of individual facial protective shields.

PMID- 19164982
TI  - Airway management in patients with facial trauma.
AB  - Management of the airway is a major concern in patients with maxillofacial trauma
      (gunshot wounds, facial fractures, cervical spine injuries, laryngotracheal
      injuries) because a compromised airway can lead to death. The method of
      intubation to use in these patients remains a controversial topic. Although there
      are many options available, each one has specific indications, and the choice
      will ultimately depend on the patient's situation and the expertise of the trauma
      team. In general, endotracheal intubation is usually not a viable option, but
      nasotracheal intubation and tracheotomies can be performed. Yet, these 2
      procedures are known to also have complications. Two interesting alternatives
      that can be opted for are the submental and submandibular intubation techniques.

PMID- 19164983
TI  - Mandibular condyle fractures: evaluation of the Strasbourg Osteosynthesis
      Research Group classification.
AB  - Condylar fractures (CFs) are about 30% of mandibular fractures. Condylar
      fractures are treated with several protocols, and unsatisfying outcome is
      achieved in some cases. A staging system for classifying CFs is of paramount
      importance to plan therapy, to define prognosis, and to exchange information
      among trauma centers. The Strasbourg Osteosynthesis Research Group proposed a
      classification system for CFs, but no report focusing to its effectiveness is
      still available. Thus, we performed a retrospective study on a series of patients
      affected by CFs.The Strasbourg Osteosynthesis Research Group classification
      defines 3 main types of CFs: diacapitular fracture (i.e., through the head of the
      condyle [DF]), fracture of the condylar neck, and fracture of the condylar base
      (CBF). A series of 66 patients (and 84 CFs) was evaluated, and age, sex, clinical
      diagnosis at admission, treatment, and outcome were considered.Fractures of the
      condylar base and DFs are the most (52.4%) and the least (4.8%) frequent
      fractures, respectively. Conversely, associated fractures of the facial skeleton
      are found in most cases of DFs (75%) and in few cases of CBFs (20.5%). Surgery
      was performed in about 15% of all cases: no DF was operated, whereas fractures of
      the condylar neck and CBFs have an open reduction and an internal rigid fixation
      in 57% and 43%, respectively. Postsurgical and late sequelae were 22.3% and 19%.
      Temporomandibular joint symptoms and malocclusion cover about 80% and 90% of
      postsurgical and late sequelae.The new classification is a simple method to
      define CFs and can give some elements about the prognosis.

PMID- 19164984
TI  - Biomaterials in craniofacial surgery: experimental studies and clinical
      application.
AB  - The increasing variety of biomaterials available to the craniofacial surgeon
      today, with advantages of "off-the-shelf availability" and lack of donor-site
      morbidity, provides a formidable armamentarium for applications in reconstruction
      and augmentation. Although biomaterials are invaluable alternatives to autogenous
      bone graft, there is lack of uniformity in clinical application. In this article,
      we review our experience with the use of hydroxyapatite derivatives in animal
      studies and subsequently discuss our experience with the use of 3 classes of
      biomaterials (cement pastes, osteoactive biomaterials, and prefabricated
      polymers) for craniofacial reconstruction. We subsequently offer guidelines to
      dictate the choice of biomaterials for different applications, based on the site
      of reconstruction (onlay versus inlay reconstruction) and skeletal maturity.

PMID- 19164985
TI  - Effect of platelet-rich plasma and fibrin glue on healing of critical-size
      calvarial bone defects.
AB  - Despite the insufficient number of experimental studies, platelet-rich plasma
      (PRP) including high amounts of growth factors is introduced to clinical use
      rapidly. The aim of this study was to compare the effects of PRP and platelet
      poor plasma (PPP) on healing of critical-size bone defects.Bilateral full
      thickness, critical-size bone defects were created in the parietal bones of 32
      rabbits, which had been studied in 4 groups. Saline, thrombin solution, PPP, and
      PRP were applied to the created defects before closure. Radiologic defect area
      measurement results at 0, 4, and 16 weeks were compared between the groups. In
      addition, densities of the newly formed bones at 16th week were studied.
      Histologic parameters (primary and secondary bone trabecula, neovascularization,
      and bone marrow and connective tissue formation) were compared between 4- and 16
      week groups.More rapid decrease in defect size was observed in groups 3 and 4
      than in groups 1 and 2, both in the 4th and 16th weeks. Newly formed bone
      densities were also found to be higher in these 2 groups. New bone formation was
      detected to be more rapid considering histologic parameters, in groups 3 and 4 at
      4th and 16th weeks.Study demonstrates that PRP and PPP might have favorable
      effects on bone healing. Although we cannot reveal any statistical difference
      between these 2 substances considering osteoinductive potential, PRP group has
      demonstrated superior results compared with fibrin glue group. Higher platelet
      concentrations may expose beneficial effects of PRP.

PMID- 19164986
TI  - Evaluation of 2 different reference planes used for the study of asymmetric
      facial malformations.
AB  - The purpose of this study was to evaluate if Frankfort plane (FH) and plane
      passing through the lateral semicircular canals (LS) can be used as reference
      planes in three-dimensional analysis.Ten patients with facial asymmetry underwent
      a three-dimensional computed tomography. Computed tomographic images were
      processed by means of a commercial software and a personal computer to obtain a
      three-dimensional virtual craniofacial model. The average Frankfort plane and the
      plane passing through the LS were identified. The distance from the above
      mentioned planes to the first upper molar and upper canine cusp was measured.It
      was not possible to detect an FH plane in any of the patients. Right FH, left FH,
      average FH, and LS plane were traced. The discrepancies among reference planes
      were significant in cases with severe asymmetry. A minimal discrepancy was
      noticed in patients with light asymmetry.In patients with severe asymmetry, the
      LS plane results in steady, reproducible, detectable, and closer to the patient's
      anatomy, representing a valid reference plane for three-dimensional computed
      tomography analysis.

PMID- 19164987
TI  - Outcome of postsurgical sequential functional exercise of jaw fracture.
AB  - BACKGROUND: A large number of studies and clinical cases show that an ideal
      prognosis for mouth function cannot be obtained without sufficient and reasonable
      postsurgical functional exercise after jaw fracture. However, no unifying
      criteria exist on postsurgical functional exercise with jaw fracture. The study
      was designed to explore effective methods of postsurgical functional exercise of
      jaw fracture. MATERIALS AND METHODS: One hundred seventeen inpatients with jaw
      fracture between August 2005 and August 2006 were subjects in this study.
      Sequential function exercise methods were used to recover patients' gape degree,
      chewing, and so on. Gape degree was recorded, and healing of the jaw was assessed
      using x-ray. RESULTS: All 117 patients with jaw fracture who underwent surgery
      were involved in the analysis. After sequential function exercise, gape degree
      and chewing function improved; good occluding relations were retained. Gape
      degree was significantly improved at 8 or 12 weeks postsurgery compared with 1 or
      4 weeks postsurgery (P < 0.01). However, no significant differences in gape
      degree were observed between 1 and 4 weeks postsurgery and between 8 and 12 weeks
      postsurgery (P > 0.05). CONCLUSIONS: Sequential function exercise contributes
      much to patient recovery of mouth function. This method is effective for
      postsurgical functional recovery of jaw fracture.

PMID- 19164988
TI  - Serial nasal bone reduction: a new approach to the management of nasal bone
      fracture.
AB  - Nasal bone fracture is the most common type of facial bone fracture. Although
      these injuries often do not seem to be severe, undertreatment of nasal trauma
      could lead to significant long-term problems. The postreduction incidence of
      nasal deformities requiring subsequent rhinoplasty or septorhinoplasty ranges
      from 9% to 50% in different studies. A clinical trial study on 330 cases with
      simple nasal bone fracture was performed. These patients were divided into 2
      groups randomly. In the case group, serial nasal bone reduction was performed,
      and in the control group, classic nasal bone reduction was performed. The failure
      rate following the initial reduction in the first visit after reduction was 14.3%
      and 14.1% in the case and control groups, respectively, but their difference was
      not significant (P > 0.05). After serial reduction in the case group (step 3),
      the failure rate was diminished to 4.19%. It was statistically superior to the
      failure rate of the control group after 1 month of follow-up (14.7%) (P = 0.001).
      Serial nasal bone reduction could be helpful to diminish the failure rate of
      nasal bone reduction.

PMID- 19164989
TI  - Obese oral and maxillofacial surgical patient.
AB  - The incidence of obesity is rising in many countries around the world. With
      obesity exerting a direct impact on oral health, more obese patients are likely
      to report for oral and maxillofacial surgical procedures. The obese patient
      population presents with unique anatomic and physiologic challenges that can
      significantly influence treatment strategies. The implications of obesity must be
      understood by the maxillofacial surgeon to avoid potential pitfalls. This study
      focuses on the relevant issues concerning obesity with regard to oral and
      maxillofacial surgery.

PMID- 19164990
TI  - Pull-out strength of multifunctional bioabsorbable ciprofloxacin-releasing
      polylactide-polyglycolide 80/20 tacks: an experimental study allograft cranial
      bone.
AB  - In this study, the pull-out forces of recently developed multifunctional
      bioabsorbable self-reinforced ciprofloxacin-releasing polylactide/polyglycolide
      (SR-PLGA+AB) 80/20 tacks were compared with plain SR-PLGA 80/20 tacks in human
      cadaver parietal bones. Pieces of parietal bone (approximately 6 x 20 cm) were
      harvested from 5 human cadavers (all were male, 29-77 years old). Fifty plain SR
      PLGA tacks (diameter, 2.0 mm; length, 6.0 mm) and 50 ciprofloxacin-releasing SR
      PLGA tacks of similar dimensions were applied to drill holes using a special tack
      shooter without tapping the drill holes. The force needed to pull the tacks from
      human parietal cadaver bones was measured using a universal tensile-testing
      machine, by tack pull-out speed of 10 mm/min. Means and SDs were calculated and
      analyzed using Student's t-test (SPSS version 10.0 for Windows). The pull-out
      forces of the ciprofloxacin-releasing and plain tacks were 147.0 +/- 5.94 and
      141.4 +/- 8.97 N respectively (P = 0.14, statistically insignificant difference
      between the 2 groups). The cause of failure in all cases was barb breakage.
      Ciprofloxacin-releasing SR-PLGA 80/20 tacks seem to have a similar holding power
      to cranial bone as plain SR-PLGA (80/20) tacks but have additional advantage of
      ciprofloxacin release.

PMID- 19164991
TI  - Innovations in military handling of facial trauma.
AB  - As the military medical treatment facilities of Operation Iraqi Freedom have
      transitioned from make-shift tent facilities to more formal fixed facilities, the
      capability to deliver more complex care has markedly improved. Using case
      presentations, the authors illustrate the integration of advances in surgical
      technology in managing complex and devastating craniofacial trauma at the 332nd
      Air Force Theater Hospital in Balad Iraq during Operation Iraqi Freedom 2006.

PMID- 19164992
TI  - Self-tapping and self-drilling screws for intermaxillary fixation in management
      of mandibular fractures.
AB  - The current study evaluated the success and the possible complication of
      intermaxillary fixation with self-tapping and self-drilling screws (STSDSs) in
      nondislocated or slightly dislocated mandibular fractures.Forty patients with
      mandibular fractures, treated with intermaxillary fixation using STSDSs, were
      clinically assessed by means of a dental vitality test and evaluation of tooth
      mobility adjacent to the cortical screw holes, and radiologically by means of a
      panoramic dental radiograph upon removal of the screws.The main complication was
      screw loss in 4.4% of cases, followed by coverage by oral mucosa in 1.2% of
      cases. However, no dental root damage, screw breakage, malocclusion, or poor
      consolidation of mandibular fractures was observed.The use of STSDSs for
      intermaxillary fixation is a useful alternative to the use of arch bars in the
      treatment of some types of mandibular fractures. In addition, there is no risk of
      dental lesions as with self-tapping screws.

PMID- 19164993
TI  - Resorbable mesh plate in the treatment of blow-out fracture might cause gaze
      restriction.
AB  - Selection of the material for the reconstruction of orbital floor defects is
      controversial. There are both autogenous and alloplastic materials, each having
      its own benefits and disadvantages. Resorbable mesh plate is one of the
      alloplastic implants. Although it has many advantages, the considerable
      complication related to the mesh is local inflammatory reaction along the
      infraorbital rim.We present a patient treated using resorbable mesh plate for the
      orbital floor fracture, in whom gaze restriction in the eye movements was
      detected because of some fibrotic bands passing through holes of the resorbable
      mesh.

PMID- 19164994
TI  - Intranasal porous polyethylene implant extrusion 7 years after insertion in a
      patient with Hashimoto disease.
AB  - We report a case of intranasal porous polyethylene implant extrusion 7 years
      after insertion in a patient with Hashimoto disease. We also discuss the possible
      causes of the extrusion and convey the histopathologic examination and
      microbiological investigation results of the samples taken from the removed
      implant.

PMID- 19164995
TI  - Relationship between small-size medial orbital wall fracture and late
      enophthalmos.
AB  - According to the result of retrospective studies for patients who have not taken
      medical treatment, most patients experience late enophthalmos and perceive their
      facial asymmetry. Thus, correct diagnosis method and concrete operative
      indication were required for medial orbital wall fracture. Retrospective
      investigation on all patients with facial trauma, who had visited the emergency
      room between January 1, 2000 and December 31, 2006, was made. Height and
      longitudinal length of the defect were obtained, and computed tomographic scan of
      the defect area was obtained. The degree of enophthalmos was measured, and
      investigation on enophthalmos and presence of facial asymmetry perceived by the
      patients was made. When the defect area of medial orbital wall fracture was 0.55
      cm, late enophthalmos of 1 mm occurred, and patients with late enophthalmos of 1
      mm or more perceived their enophthalmos and facial asymmetry. In conclusion,
      medial orbital wall fracture whose defect area is 0.55 cm or more requires
      operation.

PMID- 19164996
TI  - Microsurgical replantation for child total scalp avulsion.
AB  - Total scalp avulsion is an intractable problem in clinical practice. It often
      occurs in female adults, but rarely in children. In this article, we described
      the replantation of 2 scalp segments in a 4-year-old girl. The right segment
      involved the hairy scalp merely, whereas the left one involved the hairy scalp,
      forehead, eyelid, ear, and part of the face. Warm ischemia time was about 28
      hours, and operation time was 13 hours. Although an explorative operation was
      performed, the left segment survived partly. A relatively satisfactory aesthetic
      result was obtained by transplanting split skin from the abdomen and part of the
      survived right avulsed scalp. According to our experience, every effort should be
      undertaken to save the avulsed scalp, even in severely damaged and juvenile
      cases.

PMID- 19164997
TI  - Is there a relationship between the severity of metopic synostosis and speech and
      language impairments?
AB  - The occurrence of cognitive impairment and behavioral problems in patients with
      metopic synostosis has been described. The relationship between the severity of
      metopic synostosis and the incidence of speech and language delays has not been
      established. Twenty patients with nonsyndromic isolated metopic synostosis were
      evaluated. Five different preoperative measurements (metopic angle at the roof of
      the orbit, angle of lateral orbital wall at the sella, cranial indices, and
      distances between medial orbital walls and lateral orbital walls) were taken from
      computed tomography and compared with results from postoperative speech and
      language assessments. Frontal orbital advancement and remodeling were carried out
      by the same surgical team at a mean age of 1 year 4 months. Speech and language
      were assessed at 3 and 5 years. Six of the 20 patients had delayed speech and
      language developments. No consistent trend was observed linking the severity of
      frontal stenosis using the measured parameters with speech and language delays.
      Speech and language impairments in these patients cannot be explained by a
      physical concept, causing mechanical compression of the frontal lobes.

PMID- 19164999
TI  - Orthognathic surgery: a new preoperative informed consent model.
AB  - The authors of this study propose a new informed consent form for orthognathic
      surgery. In a previous study from 2004, a careful review of the international
      literature and clinical practice suggested the feasibility of dividing the
      informed consent form into 2 parts, one describing diagnostic procedures and
      therapeutic/surgical times, and another describing possible problems. During
      these 4 years, we noticed that this model has 2 setbacks. We replaced point 2,
      "temporomandibular joint disorders," with "postoperative temporomandibular joint
      derangement," so that the surgeon is now supposed to inform the patient on the
      possibility of condylar dislocations, condylar sag, and clockwise/anticlockwise
      rotations of occlusal surface after surgery. We also changed point 5, "tooth and
      periodontal disease," in "tooth damage, avulsion, and periodontal disease"
      because we believe patients should be informed better on the risk of injuries to
      the dental elements such as fractures, luxations, or avulsions, especially to
      incisors. In the opinion of the authors, this new informed consent form allows
      the patient to know the risks related to the orthodontic/surgical therapy better,
      thus preserving the surgeons from the civil risk and penalties of omission.

PMID- 19165000
TI  - Endoscopic release of unicoronal craniosynostosis.
AB  - We demonstrate a novel method of endoscopic frontal-orbital advancement for the
      treatment of unicoronal craniosynostosis. The evolution of this cranioplasty
      modality burrows from an established precedent of safety and technical experience
      in strip craniectomies and endoscopic brow surgery. The procedure facilitates
      osteotomies similar to open frontal-orbital advancement and uses reabsorbable
      materials to achieve immediate intraoperative correction of unicoronal
      craniosynostosis through smaller incisions. The patients in the study underwent
      endoscopic frontal-orbital advancement and cranial vault remodeling. This was
      made possible with the use of a novel ultrasonic bone saw that permits
      osteotomies to be made with minimal disruption to the dura matter. After full
      frontal-orbital advancement, immediate reabsorbable fixation was used to
      stabilize the advancement as in the open technique. There were no major
      complications. All patients demonstrated improvement in plagiocephaly due to
      unilateral coronal synostosis. Patients and their families reported a 100%
      patient satisfaction and an improvement in cranial asymmetry from 10 to 2 mm (P <
      0.5). This is a new endoscopic cranial vault remolding technique that achieves
      state-of-the-art correction of unicoronal craniosynostosis with less morbidity
      and mortality.

PMID- 19165001
TI  - Evaluation of clinical prognostic factors in T1 N0 M0 head and neck basal cell
      carcinoma.
AB  - This retrospective study was carried out to assess the clinical outcome of stage
      I (ie, T1 N0 M0) head and neck basal cell carcinoma (HNBCC) and verify the impact
      of some clinical parameters on prognosis. The cases of 220 patients with stage I
      (ie, T1 N0 M0) histologically proven HNBCC were analyzed.The global disease
      specific survival rate at 36 months was 100%, irrespective of the type of
      surgery, and thus, it was demonstrated that radical tumor resection is a viable
      procedure for stage I HNBCC. However, 11 (5%) of 220 cases had a recurrence. A
      second procedure was performed in 10 (90.9%) of 11 cases. In 3 of the 10 patients
      operated on twice (30%), a second recurrence was detected. Thus, a second
      surgical procedure on a recurring tumor is possible, but the multimodality
      treatment regimen should be considered for recurring tumors.

PMID- 19165002
TI  - Principles of facial trauma: orbital fracture management.
AB  - Often, complex, optimal management of the orbital fracture is directly dependent
      on thorough initial evaluation, correct injury assessment, and timely initiation
      of chosen therapy. Most often, secondary to assault or motor vehicle collision,
      these fractures are frequently associated with additional traumatic injury. With
      recent advances in imaging, alloplastic materials, and bone fixation technology,
      the evolution of orbital fracture management now enables reconstruction of even
      the most severe injuries.

PMID- 19165003
TI  - Mandibular angle ostectomy for Chinese women: approaches and extent determined by
      cephalometric analysis.
AB  - Giving a square and muscular appearance, a prominent mandibular angle is
      considered to be unattractive in the Orient. Because of the different aesthetic
      sensitivities, the problem is reported more frequently in the Orient than that in
      the West. In most reports, the final choice of surgical procedure, including the
      approach, position of ostectomy, and volume of bone to be cut, depended
      subjectively on the experience of the surgeon and the desire of the patient. This
      article provides a study to make the surgical procedure accurately and
      objectively, involving 46 female patients asking for reduction of prominent
      mandibular angle for cosmetic reasons. Measurement and analysis of cephalometric
      radiographs were performed preoperatively. According to the different
      characteristics of the prominent mandibular angle in front and lateral views of
      the radiographs, the patients were classified into 4 types. In each type,
      ostectomy of different extent via different approaches or masseter botulinum
      toxin A injection only was given. Postoperative cephalometric analysis was also
      made to evaluate the result objectively. The results have been generally
      satisfactory.

PMID- 19165004
TI  - Speech evaluation after repair of unilateral complete cleft palate using modified
      2-flap palatoplasty.
AB  - Two-flap palatoplasty using mucoperiosteal flaps is becoming popular for wide
      cleft palates. We found that elevation of the cleft-side mucoperiosteal flap was
      sufficient to close the defect without elevation or relaxing incision in the
      noncleft side when performing 2-flap palatoplasty for a complete unilateral cleft
      palate. We have termed this modified 2-flap palatoplasty. The present study
      compared speech after classic and modified 2-flap palatoplasty for unilateral
      complete cleft palate. METHODS: Of 31 unilateral complete cleft lip and palate
      patients, 16 underwent the classic 2-flap palatoplasty between September 1998 and
      September 2000, and 15 underwent modified 2-flap palatoplasty between November
      2000 and November 2002. Postoperative speech evaluation was undertaken by a
      speech pathologist. Patients with functional speech problems such as
      hypernasality or compensatory articulation were recommended for speech therapy.
      In cases where speech therapy did not result in normal speech, patients underwent
      secondary velopharyngeal surgery and further speech therapy. RESULTS: Fifteen of
      16 patients who underwent the classic procedure were followed up, of which 5
      showed hypernasality or compensatory articulation upon speech evaluation. Four of
      those patients required secondary velopharyngeal surgery. All 15 patients who
      underwent the modified procedure were followed up. Six of those patients showed
      hypernasality or compensatory articulation, of which 2 required secondary
      velopharyngeal surgery. There was no statistically significant difference between
      the classic and modified groups in terms of palatal fistula rate, speech, and
      secondary surgery rate. CONCLUSIONS: There was no difference between the classic
      and modified 2-flap palatoplasty in terms of postoperative palatal fistula rate,
      speech, and secondary surgery rate. Because of the advantages of the modified
      procedure in terms of fewer incisions, these findings indicate that larger long
      term studies are warranted, particularly to evaluate maxillary bone growth.

PMID- 19165006
TI  - Diagnosis and treatment of familial cherubism characterized by early onset and
      rapid development.
AB  - Cherubism is a benign maxillary bone dysplasia of childhood, usually showing an
      autosomically dominant inheritance with variable penetrance and spontaneously
      resolving after puberty. Only maxillary bones are affected and develop
      pseudocystic osteolytic lesions. This article presents an early and rapidly
      evolving familial case of cherubism. The 3-year-old child underwent conservative
      curettage of lesions, with a conservative approach that allowed a normal
      permanent dentition in adolescence. Family history revealed that the father had
      been treated for similar lesions between 14 and 21 years of age, but the late
      treatment caused edentulism. In conclusion, although cherubism represents a
      benign and localized maxillary dysplasia, it requires prompt surgical but
      conservative treatment and careful follow-up to avoid permanent lesions, that is,
      malocclusion and/or edentulism.

PMID- 19165007
TI  - Frontobasal suture distraction corrects hypotelorism in metopic synostosis.
AB  - BACKGROUND: Spring-assisted cranioplasty has been demonstrated to correct
      hypotelorism associated with metopic synostosis. In addition, the fronto-orbital
      axis rotates toward a more normal orientation. We postulated that spring-induced
      shear forces and subsequent displacement across the frontobasal sutures are the
      primary initial mechanisms for change in cranio-orbital morphology. METHODS:
      Sixteen consecutive patients (32 orbits) with trigonocephaly operated on between
      1999 and 2004 were studied retrospectively. After frontal remodeling, a spring
      was placed across the released metopic suture. Preoperative and 6-week
      postoperative cephalograms were used to measure the relative translation of the
      medial orbital wall from the midline at fixed vertical distances above and below
      the frontoethmoidal suture (FES). The vertical height of the spring above the
      frontonasal suture and the patient's age were analyzed with respect to the
      increase in bony interorbital distance (BIOD). RESULTS: There were significant
      increases in movement of the medial orbital wall above the FES at each
      measurement point (P < 0.001). There was no significant postoperative movement of
      the medial orbital wall below the FES at any measurement point. The relative
      movements above the suture suggest a degree of plastic deformation adjacent to
      the suture.There was no significant correlation between the age of patient or the
      height of the spring above the frontonasal suture and the increase in BIOD.
      CONCLUSION: Tensile spring forces are transmitted directly to the frontoethmoid
      suture. Most initial increases in BIOD and altered intraorbital morphology are
      due to distraction of cranial base sutures rather than plastic deformation.

PMID- 19165008
TI  - Review of pediatric migraine headaches refractory to medical management.
AB  - OBJECTIVE: The surgical treatment of migraine headache is a recent innovation
      that has broadened the potential patient population who may benefit from
      craniofacial surgical techniques to millions of affected adults. However, the
      population at risk in the pediatric age group has not been clearly established.
      The present retrospective review was performed to provide demographic information
      of the adolescent migraine in a major children's hospital. This information is
      essential before considering surgical treatment of migraine in this age group.
      METHODS: Five hundred eighty-eight charts of patients aged 12 to 18 years who
      presented to the pediatric neurology clinic with headache in 2006 were
      retrospectively reviewed to evaluate for the diagnosis of migraine. Data
      collected included headache location, frequency, duration, intensity, associated
      migraine symptoms, and headache precipitants, as well as the response to medical
      treatment. RESULTS: Two hundred ten (36%) of 588 patients had the diagnosis of
      migraine headache, and 51 patients (24%) were considered refractory to the
      medical treatment offered. In 101 of the 210 migraine patients, anatomic location
      of the headaches could be identified. Thirty-nine children (19%) with refractory
      migraines (mean age, 14.7 years [SD, 0.3 years]) reported definitive migraine
      triggers. CONCLUSIONS: A significant percentage of pediatric patients with
      migraine headache remain refractory to medical treatment. At present, there is no
      good treatment regimen for migraine headaches in the pediatric population. We
      believe that surgical treatment of migraine headaches may be a realistic option
      for these patients.

PMID- 19165009
TI  - Evolution of surgery for sagittal synostosis: the role of new technologies.
AB  - BACKGROUND: Techniques for sagittal synostosis correction continue to evolve to
      improve outcomes and minimize morbidity. The techniques now used by our
      craniofacial service are spring-assisted cranioplasty for younger children
      (generally up to 9 months of age) and biparietal barrel staving with cross-struts
      using bioabsorbable plates for older children. We evaluate the evolution of, and
      rationale for, our current methods of treatment. METHOD: All patients who
      underwent surgery for craniosynostosis over the period 1982 to 2007 were
      retrospectively reviewed. Patients with sagittal synostosis were analyzed
      according to the type of operative procedure performed. Blood loss, operative
      time, and hospital stay were compared between techniques using analysis of
      variance. RESULTS: Seventy-one patients had a cranial vault remodeling procedure
      for craniosynostosis. Thirty-four patients had sagittal synostosis with
      scaphocephaly. During the period 1982 to 2000, 13 patients had a strip
      craniectomy, and 5 patients had a barrel stave and morcellation procedure. Since
      2001, the cross-strut technique using bioabsorbable plates has been used in 7
      patients. In 2005, the spring cranioplasty technique was introduced and has been
      used in 9 patients. There were no deaths and no serious complications. One
      patient treated with springs had a second spring procedure performed to further
      increase biparietal width. Spring-assisted cranioplasty had a significantly
      shorter operating time than other techniques (P < 0.01). CONCLUSION: The
      availability of both absorbable plates and expansile cranial springs has
      revolutionized the techniques our unit uses for scaphocephaly correction. Our
      early experience with these techniques has shown that the techniques are reliable
      and give good cranial shape and form with minimal treatment morbidity.

PMID- 19165010
TI  - Adnexal skin carcinomas of the face.
AB  - Skin adnexal neoplasms are rare tumors, and knowledge on their exact histological
      development and pathogenesis remains fragmented. Their diagnosis and management
      are frequently troublesome, especially for malignant tumors. We present a
      retrospective case series of malignant appendageal tumors of the face. Records of
      patients with histologically confirmed adnexal skin carcinoma managed at a single
      department during the period 1995 to 2004 were reviewed. Patient biodata,
      surgical management, and main outcome measures such as locoregional recurrence,
      distant metastasis, and disease-free and overall survival were recorded.Eleven
      patients were identified from record analysis. Lesions were mainly located at the
      eyelids and the nose. All patients were managed with wide local excision and
      restoration with local flaps. Two patients showed regional metastasis and
      underwent radical neck dissection. Nine of 11 patients were alive and free of
      local and/or regional disease on final follow-up. Two patients died of causes
      unrelated to the disease. Clinical and histological features, tumor biological
      behavior, diagnostic difficulties, and recommended management are discussed.In
      conclusion, adnexal skin tumors should be considered in the differential
      diagnosis of skin tumors, particularly in view of their more sinister prognosis
      compared with other nonmelanoma skin tumors. They are acknowledged to demand a
      more aggressive plan of surgical treatment.

PMID- 19165011
TI  - Maternal reports of satisfaction with care and outcomes for children with
      craniosynostosis.
AB  - Craniosynostosis is a congenital deformity caused by premature fusion of cranial
      suture(s). Surgical outcomes of craniosynostosis have been well documented;
      however, limited published data are available regarding access to care and social
      and psychological health outcomes for children with craniosynostosis. The authors
      conducted a population-based, multistate study of maternal perceptions of care
      and outcomes for children with craniosynostosis born from January 1998 through
      December 2003. Mothers of 147 children were contacted and asked to complete a
      structured telephone interview; 82 mothers (55.8%) participated. Overall, the
      mean ages of children and their mothers at the time of interview were 4.4 and
      34.8 years, respectively. Mothers interviewed tended to be white and, at a
      minimum, high school graduates. Most mothers reported being satisfied with the
      craniosynostosis-related information and support provided by medical care
      providers, and access to primary and specialty care was most often rated as
      satisfactory. Mothers tended to report the physical health of their child to be
      good; however, delays in cognitive and emotional development, hearing loss, and
      speech problems were identified. In addition, statistically significant
      differences among mothers in each state were noted for reports of the quality of
      team care, primary care, learning interventions, and perceived need for
      additional surgeries. These results suggest some limitations in craniosynostosis
      related care and provide guidance to medical and surgical care providers in
      making need-based improvements in craniosynostosis surgery and care. Future
      studies are recommended to replicate this evaluation in additional populations.

PMID- 19165012
TI  - The managements of orofacial tumors of children in Iraq.
AB  - These studies were carried out in the maxillofacial unit, surgical specialties
      hospital, medical city, Baghdad, included 55 patients with orofacial tumors;
      their ages ranged from 2 days to 14 years (mean, 7 years). Twenty-eight of them
      were girls, and 27 were boys. Tumors included 20 cases of benign tumors and 35
      cases malignant. Treatment modalities ranged from complete surgical excision,
      surgical shaving operations, and deep x-ray therapy (DXT; radiotherapy) for some
      benign tumors. The management of malignant tumors was carried out by the use of
      chemotherapy, chemotherapy and DXT to radical surgery, or radical surgery with
      DXT. Reconstruction of the mandible was carried out using a rib graft or a block
      of a corticocancellous bone graft from the iliac crest with reimplantation of the
      condyle after resection from the tumor and fixed by rigid fixation to the bone
      graft. Temporary reconstruction of the mandible done by Kirschner wire for
      malignant tumors required a postsurgical DXT. A temporalis muscle flap was used
      for the augmentation of the orbit with a frontoorbital flap after radical
      excision of a malignant tumor of the orbit, and a silastic implant (silicon
      rubber) was used for reconstruction of the orbital floor. A long-term follow-up
      ranged from 2 to 15 years. The aim of this study was to present a certain number
      of cases with an interesting pathologic tumor condition showing peculiar
      behaviors; the management of these cases was a challenge to our surgical
      experience.

PMID- 19165013
TI  - Basaloid squamous carcinoma of mandible.
AB  - Basaloid squamous carcinoma is a rare distinct histologic variant of squamous
      cell carcinoma of the head and neck region. Basaloid squamous carcinoma is more
      aggressive and has a poorer prognosis, although histologically, it is associated
      with squamous cell carcinoma and squamous atypia. The usual site of occurrence
      for basaloid squamous carcinoma is the base of the tongue, hypopharynx (pyriform
      sinus), and the supraglottic larynx (Wain et al. Hum Pathol 1986;17:1158-1166).
      We are reporting an unusual case of basaloid squmous carcinoma of the mandible
      with no secondaries and features of sarcomatoid pattern histologically.

PMID- 19165014
TI  - Endoscopic approach to maxillofacial trauma.
AB  - Endoscopic approaches to maxillofacial trauma have included their use in
      temporomandibular joint arthroscopy, zygomatic arch repair, repair after orbital
      trauma, repair of frontal sinus fractures, and finally in the repair of
      subcondylar mandibular fractures. These techniques provide exciting new options
      for the management of facial fractures. Many of the techniques provide a steep
      learning curve and require specialized equipment. The approach to an orbital
      blowout fracture allows the use of a Caldwell-Luc approach and the use of a
      naturally occurring body space (the maxillary sinus) for the visualization and
      maneuvering of the endoscope, tools, and implants. The use of the endoscope in
      the management of fractures for facial structures such as mandibular subcondylar
      fractures, which do not have a naturally occurring body cavity, may present
      greater challenges when trying to obtain visualization, reduction, and fixation.
      When used for the treatment of subcondylar fractures, wide exposure and the use
      of right-angled drills and screw drivers may significantly help with this
      procedure. This may be considered by some surgeons as an endoscopically
      "assisted" procedure that can possibly be accomplished with direct visualization
      and the use of dental mirrors. It remains to be seen as to whether some of these
      diverse endoscopic applications will represent the standard of care in the future
      or remain a specialized technique practiced by a minority of surgeons in a few
      specialized centers. This article reviews various endoscopic applications to
      maxillofacial trauma and discusses some of the controversies of these techniques.

PMID- 19165015
TI  - Flip-registration procedure of three-dimensional laser surface scanning images on
      quantitative evaluation of facial asymmetries.
AB  - The aim of the study was to find a proper method that may evaluate the severity
      of facial asymmetry quickly and accessibly in clinics. METHODS: The three
      dimensional image data of facial asymmetry patients were collected with three
      dimensional laser surface scanning, and the desired therapy outcomes were
      simulated in computers by flip-registration procedure. The discrepancy between
      desired results and initial images was calculated automatically, and a colored
      hypsography was printed. A questionnaire was given to both the patient and the
      craniofacial surgeon to examine the symmetry, accessibility, achievability, and
      helpfulness of these outcomes. RESULTS: The three-dimensional image data offered
      by laser surface scanning were accurate and convenient. The desired results were
      reliable and acceptable to the patients. The colored hypsography was clear and
      accessible and achieved high appreciations from the surgeons. CONCLUSION: Three
      dimensional laser surface scanning together with flip registration procedure can
      evaluate the severity of facial asymmetry quickly, quantitatively, and
      effectively with an achievable outcome. It is welcomed by the craniofacial
      surgeons and has a great potential in clinic application.

PMID- 19165016
TI  - Influence of orthognathic surgery on voice fundamental frequency.
AB  - Considering that orthognathic surgery promotes changes in orofacial structures
      constituting the resonating system, functional changes secondary to surgery are
      expected to affect speech, leading to the need for further speech and voice
      adjustments. Thus, understanding the possible relationships of these structures
      with voice production is important. Therefore, this study aimed to describe the
      changes in voice fundamental frequency of a patient submitted to orthognathic
      surgery and observe if there is a relationship with hyoid bone positioning at the
      different treatment periods. The results revealed that voice fundamental
      frequency increased after surgery, returning to values close to the preoperative
      condition, which corresponded to vertical movement of the hyoid bone.

PMID- 19165017
TI  - Infratemporal metastasis from occult follicular thyroid carcinoma.
AB  - An extremely rare case that has not been reported before is described in which
      metastasis of a follicular carcinoma of the thyroid is resected from the
      infratemporal fossa. The patient had not been diagnosed of this thyroid
      pathology. She underwent a left subtemporal preauricular approach, but after
      this, she had another subtemporal preauricular approach with total thyroidectomy,
      a facial translocation by degloving, and an endoscopic surgery, because of a
      local recurrence, and a sella turcica and sphenoidal sinus metastasis. Six years
      after this, the patient was free of recurrence. Surgical excision of metastatic
      thyroid lesions may be the only effective treatment but always followed by
      suppression therapy and whole-body iodine I 131 internal radiation. Stereotactic
      radiosurgery is a feasible option to treat skull base metastasis of this kind of
      tumor.

PMID- 19165018
TI  - Do expansile cranial springs erode through the cranium?
AB  - Expansile cranial springs are used in selected cases of craniosynostosis. The
      spring exerts moderate force against the relatively thin skull. We investigated
      whether the spring erodes through the bone and the clinical significance of any
      erosion relative to the cranial expansion achieved. METHODS: New Zealand white
      rabbits (n = 10) underwent sagittal suturectomy and spring insertion. Amalgam
      markers were placed perpendicular to the expected direction of suture erosion. A
      control group (n = 10) underwent suturectomy. Radiological evaluation was
      performed for 7 weeks to check for migration of the spring foot. RESULTS: The
      mean cranial thickness was 1.4 mm at the site of spring insertion. This compared
      with 1.8 mm in 7 children undergoing spring cranioplasty. The mean spring force
      was 9.4 N. In sagittal synostosis, the mean spring force used is 7 to 10 N.The
      cranial width increased 11.02 mm in the spring treatment group compared with 0.23
      mm in the control group (P < 0.001). Spring erosion occurred in 4 (20%) of the 20
      spring ends. Mean spring erosion for the treatment group was 0.18 mm. This was
      3.2% of the mean increase in cranial width. The maximum percentage spring erosion
      versus cranial expansion in an individual rabbit was 14.17%. There was no
      statistical difference in cranial expansion between the rabbits in whom bone
      erosion did and did not occur. CONCLUSIONS: The degree of spring force required
      to effectively expand the cranium may cause bone erosion in some individuals.
      This degree of spring erosion was of minimal clinical significance in this animal
      model.

PMID- 19165021
TI  - Individualized template-guided remodeling of the fronto-orbital bandeau in
      craniosynostosis corrective surgery.
AB  - Reshaping of the forehead and fronto-orbitlal bandeau in the correction of
      craniosynostosis requires careful attention to the ideal craniofacial
      proportions. Osteotomies guided by standard templates have been described to
      correct deformities of the fronto-orbital bandeau and forehead. We have used an
      individualized template as a guide to correction by osteotomy and remolding, in
      cases of craniosynostosis affecting the anterior cranium. This is a prospective
      study examining the use of an individualized template to correct the forehead and
      facial shape in a consecutive series of 15 craniosynostosis cases over a 6-month
      period. No significant differences for the group were found between the ideal
      individual template measurements and those actually achieved at the completion of
      surgery. The use of individualized templates guiding meticulous forehead
      remodeling allows for the normalization of craniofacial appearance in the
      correction of craniosynostosis.

PMID- 19165019
TI  - Expression of inducible nitric oxide synthase and vascular endothelial growth
      factor in ameloblastoma.
AB  - The purposes of this study were to determine the correlation between the
      expression of inducible nitric oxide synthase (iNOS) and vascular endothelial
      growth factor (VEGF) in ameloblastoma and to examine the relationships of this
      expression to angiogenesis and the clinical and biological behaviors of the
      tumor. Immunohistochemical staining with streptavidin peroxidase was used to
      analyze iNOS and VEGF expression, and CD34 was used to evaluate microvascular
      density (MVD) in 35 ameloblastomas (24 primary tumors and 11 recurrences) and 5
      malignant ameloblastomas. Ten odontogenic keratocysts (OKCs) served as controls.
      On relational analysis, positive and VEGF expression and MVD counts increased in
      this order: OKCs, primary ameloblastoma, recurrent ameloblastoma, and malignant
      ameloblastoma. Differences between the ameloblastomas and OKCs were significant
      (P < 0.05). Among ameloblastomas, MVD counts increased with increasing expression
      of iNOS and VEGF (P < 0.05), and iNOS expression and VEGF expression were
      positively correlated (r = 0.66, P < 0.05). Inducible nitric oxide synthase
      expression and VEGF expression may be closely related to the angiogenesis and
      invasive biological behavior of ameloblastomas.

PMID- 19165022
TI  - Open surgery versus endoscopic surgery in benign neoplasm involving the frontal
      sinus.
AB  - The frontal sinus, because of its proper anatomic features, has a particular
      relation with nasal cavities. Indeed, its anatomic opening (ostium) is strictly
      related to a complex ethmoidal structure prechamber mainly composed of the
      frontal recess.This constitutional feature makes the endoscopic approach more
      complex in comparison with other major sinuses treatment.In the following work,
      we present a systematization of surgical approach in relation to different
      pathologies, analyzing differences and results throughout the comparison of 2
      groups: one treated with the endoscopic approach, and the other with open
      surgery.From these observations, we can assess that surgical approach choice must
      consider several parameters such as neoplasm localization, extension, dimension,
      and frontal recess anatomic features.

PMID- 19165023
TI  - Cranial reshaping using methyl methacrylate: technical note.
AB  - Reconstruction of the facial skeleton and cranial vault has always posed
      difficult problems. To obtain a good result, various autologous, homologous, and
      heterologous grafts and biomaterials can be used. In this work, the authors
      present their experience in the use of methyl methacrylate (MMA) presenting a
      simple technique for application of the material that reduces the risk of
      complications. The authors also performed a review of the international
      bibliography relative to the use of MMA as an autologous bone substitute,
      analyzing the risks, complications, and results obtained.Between October 2003 and
      September 2007, the authors used MMA in procedures of cranial reshaping on 9
      patients who underwent surgery to repair the damage caused by cranial-facial
      traumas and malformations.The technique of layered application of MMA made it
      possible to obtain excellent aesthetic and functional results in 8 patients,
      whereas in 1 case, the material had to be removed when the patient developed
      complications due to infection.Methyl methacrylate still remains the material of
      choice for cranioplasty on adult patients. The application of the material and
      sequenced layers makes it possible to reduce perioperative complications to the
      utmost, providing an excellent aesthetic and functional result.

PMID- 19165024
TI  - Evolution in diagnosis and repairing of orbital medial wall fractures.
AB  - In the last decades, diagnostical imaging, surgical techniques, alloplastic
      materials, and surgical instruments development allowed a great progress in
      management of orbital fractures; the aim of the present study was to focus on the
      progress and changes in the management of orbital medial wall fractures. Isolated
      medial wall fractures are not a common clinical evidence, and those necessitating
      surgery is relatively rare. Diagnostical refinements allowed to detect such
      fractures more commonly than suspected, and the indications to surgical treatment
      had been increased by the progresses that minimized morbidity of patients and
      allowed better restoration of the functional anatomy. Mainly, the endoscopic
      surgery as an alternative to open reduction allowed to manage such fractures with
      less unwanted sequelae; endoscopy decreases morbidity and improves the results
      with respect to open reductions. In literature, currently, it can be noticed that
      there is an increased trend in surgical treatment of the patients with orbital
      medial wall fracture because endoscopy decreased perisurgical morbidity and
      improved long-term results. Endoscopic repair of orbital blowout fractures
      represents an innovative and highly successful and safe alternative to external
      repairs owing to its introduction in orbital trauma management; actually,
      indications for surgical intervention are in the course of revision. New deal is
      important for the future treatment of patients sustaining orbital trauma. The
      authors present their experience.

PMID- 19165025
TI  - New technique for reconstructing the affected cranium and orbital rim in
      unicoronal craniosynostosis.
AB  - Of the single-suture craniosynostoses, unicoronal synostosis (UCS) is widely
      acknowledged to represent the most varied and complex set of craniofacial
      deformities. This is attributed to the endocranial base being affected along with
      the coronal suture. This deformity may present with both coronal and
      frontosphenoidal synostosis and has been associated with elevated intracranial
      pressure; brain morphological abnormalities; vertical dystopia; ambylopia;
      malformations of the forehead, orbit, midface, and mandible; and behavioral,
      cognitive, and speech abnormalities. It is the variable structural presentation
      coupled with the long-term stability of the reconstruction that forms a complex
      reconstructive challenge. Our surgical technique concordantly addresses these
      associated structures beyond the isolated coronal suture. Although several
      surgical techniques have previously been described, there remains no consensus
      toward a preferred surgical approach to this dynamic and three-dimensional
      problem. We describe our technique of coronal and frontosphenoidal synostosis
      release as part of a frontotemporoparietal bone flap, release of the entire
      fronto-orbital rim, and use of the unaffected skull to reconstruct the affected
      half of the skull. The purpose of our study was to describe our surgical approach
      to UCS. It has been our experience that optimal correction of UCS must address
      the associated anomalies beyond the affected coronal suture and must be stable
      over time.

PMID- 19165026
TI  - A new glabellar flap modification for the reconstruction of medial canthal and
      nasal dorsal defects: "flap in flap" technique.
AB  - BACKGROUND: In considering periorbital reconstructive options, the goals of
      reconstruction are to obtain functional and esthetic results. At the medial
      canthus, reconstruction should maintain the normal concavity of the canthus
      without distortion of the surrounding tissues and should maintain normal eyebrow
      contour and symmetry. The authors represent their flap in flap technique that
      provides normal concavity of the canthus and does not cause any complex and
      undesirable scars. METHODS: A new modification of conventional glabellar flap
      which was named "flap in flap technique" was raised to cover medial canthal
      defect. We designed an inverted V-shaped advancement flap (123Delta-A flap) that
      contains both B (145Delta flap) and C (2345) flaps. The B flap is designed in the
      glabellar region, which is at medial side of the defect and is transposed to
      defect, and the C flap is planned in V-Y fashion to release tension over the B
      flap. RESULTS: To date, we have used this technique successfully in 5 patients (4
      women and 1 man), requiring a glabellar flap to reconstruct the medial canthus
      and proximal nasal dorsum. All defects were secondary to excision of basal cell
      carcinoma. All were satisfied with the cosmetic and functional results.
      CONCLUSIONS: Our glabellar flap in flap technique for the reconstruction of
      medial canthal defects has several advantages such as maintaining concavity of
      the canthus without distortion of the surrounding tissues and providing normal
      eyebrow contour and symmetry.

PMID- 19165027
TI  - Use of dental mirror in microsurgical practice.
AB  - In this article, we introduce the use of dental mirror during microsurgery. We
      have been using no. 4 dental mirror during microvascular anastomoses and nerve
      coaptations for the last 6 months successfully and found that, as a cheap and
      easily obtainable instrument, it has facilitated our practice. We are strongly
      recommending the use of dental mirrors in microsurgical practice and inclusion to
      every microsurgery instrument set.

PMID- 19165028
TI  - Nevoid Basal cell carcinoma syndrome: a cephalometric study of patients and
      controls.
AB  - Craniofacial morphology of patients with nevoid basal cell carcinoma syndrome
      (NBCCS) has sometimes been reported at clinical examination, but any
      investigation has described it on the basis of cephalometric measurements.The
      purpose of this study was to conduct a cephalometric analysis of patients with
      NBCCS and to compare measurements with non-NBCCS subjects of similar ages, to
      elucidate if there is any relationship between NBCCS and craniofacial
      morphology.The study population consisted of 14 adult patients (9 men and 5
      women), ranging in age from 18.2 to 56.8 years, with the diagnosis of NBCCS, with
      good-quality lateral cephalometric radiographs, and 14 adult healthy patients
      matched for age and sex to the NBCCS group. Cephalometric measurements were
      carried out on radiographs, and measurements of angles and distances were
      performed.Statistical differences between NBCCS subjects and controls were
      observed. Data analysis displayed that the measurements of the anterior cranial
      base (P <or= 0.0043), mandibular length (P <or= 0.0168), and maxillary length (P
      <or= 0.0284), posterior facial height (P <or= 0.0406), and of mandibular angle (P
      <or= 0.0026), facial axis angle (P <or= 0.0402), lower facial height angles (P
      <or= 0.0135), and of interincisal angulation (P <or= 0.0148) were higher in NBCCS
      subjects in respect to controls. On the contrary, the facial convexity (P <or=
      0.0189) and the mandibular arc angle (P <or= 0.0378) were reduced in NBCCS
      subjects.According to these findings, NBCCS patients presented a sagittal
      lengthening of the anterior cranial base and maxilla and a vertically and
      horizontally overdeveloped mandible, together with the features of a long-face
      syndrome with a large gonial angle.

PMID- 19165029
TI  - Morphological parameters of the periorbital arterial arcades and potential
      clinical significance based on anatomical identification.
AB  - The aim of the study was to investigate the locations, diameters, and connections
      of the periorbital arterial vessels. The peripheral and marginal arcades of the
      superior and inferior eyelids were revealed by bilateral meticulous anatomic
      dissections in 12 adult male and 5 female preserved cadavers. Silicone rubber
      injection was used to fill the regional arteries. The mean external diameter of
      the lacrimal (0.4 mm), supraorbital (1.0 mm), supratrochlear (0.9 mm), superior
      medial palpebral (0.9 mm), inferior medial palpebral (1.0 mm), dorsal nasal (0.8
      mm), and infraorbital (2.0 mm) arteries were measured. Contribution of
      superficial temporal artery to palpebral arcades via frontal, zygomatico-orbital,
      and transverse facial branches was demonstrated. The purpose of this study was to
      demonstrate the periorbital arterial supply with contributing anastomosis from
      facial vasculature and impact on clinical practice.

PMID- 19165030
TI  - Extracranial microanatomic study of supraorbital keyhole approach.
AB  - OBJECTIVE: The extracranial microanatomic features and tissue protection for
      supraorbital keyhole approach are described in detail to achieve less
      invasiveness, which has scant reports and is important for craniofacial surgeons.
      METHODS: Ten formalin-fixed human cadaveric heads were used in 20 sides, by means
      of an operating microscopic, with microinstruments and magnification ranging from
      3x to 16x. The relationship between concerned nerves, muscles, and bone window
      was identified and measured. RESULTS: The height from the musculus orbicularis
      oculi superiorus to the incision on the arch of the eyebrow is 6.9 +/- 1.0 mm.
      The horizontal distance from the anterior ramus of the temporal branch of the
      facial nerve to the frontal zygomatic process is 19.5 +/- 3.6 mm. Thus, the
      supraorbital keyhole approach incision can potentially injure the nerve. However,
      the lateral branch of the supraorbital nerve is outside the pericranial layer and
      has no ramus within 10 mm from its emission, and the angle from the lateral
      branch of the supraorbital nerve to the ridge of the orbit is 74 +/- 3 degrees.
      Therefore, the supraorbital nerve can be dissected to enlarge the medial region
      of the bone window. We propose to form the muscle-bone flap to keep adhesion of
      the temporal muscle and gain cosmetic benefit. CONCLUSINS: Our microanatomic
      study of the musculus orbicularis oculi, the temporal branch of the facial nerve,
      the superior orbital nerve, and the temporal muscle suggests a means to minimize
      invasiveness and gain cosmetic benefit.

PMID- 19165031
TI  - Examination of the heads of the lateral pterygoid muscle on the temporomandibular
      joint.
AB  - The lateral pterygoid muscles (LPMs) function as a unit during precise mandibular
      positioning movements that occur during such activities as speech, singing, or
      playing musical instruments. The LPM has been the focus of an attempt to explain
      problems associated with the temporomandibular joint and anterior displacement of
      the meniscus of the joint. The aim of the study was to define the general
      morphology, describing the position and shape of the heads of the LPMs. In the
      course of dissection, the heads of the LPMs were noted, as well as the pattern,
      position of the origin and insertion, and course under 2.5x loupe magnification
      in 25 adult male human cadavers. The LPM has the general form of an irregular
      pyramid that narrows progressively toward the front. As a result of the
      macroscopic examination, the LPM was found to originate, with 3 heads as the
      superior LPM (SLPM), the inferior LPM (ILPM), and inner LPM. It was realized that
      the ILPM width was 3 times more than that of the SLPM. The SLPM ending fibers of
      LPM had a more tendinous structure compared with the ILPM ending fibers. The SLPM
      and ILPM were observed as being adhered mostly to the pterygoid fovea. The study
      has shown that the muscle has atypical penniform structure made up of 8 tendinous
      layers that were particularly well developed. It is an indisputable fact that the
      success in surgical strategy and planning mainly relies on the surgeon's
      knowledge of the variable origins and insertions of the LPM.

PMID- 19165032
TI  - Anatomic study using three-dimensional computed tomographic scan measurement for
      truncal maxillary nerve blocks via the suprazygomatic route in infants.
AB  - A maxillary nerve block using external anatomic landmarks is a safe regional
      anesthesia for adults. However, the classic approach to the nerve may be
      difficult in infants. To use this block in infants, we describe the anatomical
      landmarks needed to reach the foramen rotundum area using the suprazygomatic
      route.Computed tomographic scans of 55 infants (mean age, 8.5 months; range, 1
      week to 16 months) without any malformation were retrospectively evaluated using
      multimodal and multiplanar software. For each side, the distances and angles from
      the skin to the greater wing of the sphenoid and to the foramen rotundum area
      (representing the maxillary nerve) were measured in the axial and oblique
      planes.The distances from the skin at the frontozygomatic angle to the greater
      wing of the sphenoid in the axial plane and the foramen rotundum area in the
      oblique plane are 24.1 mm +/- 2.7 and 47.4 mm +/- 4.1, respectively. From the
      skin landmark, the direction of the trajectory was oriented 19.3 +/- 5.3 and 8.7
      +/- 2.9 degrees forward. These distances and angles must be slightly adapted for
      infants younger than 6 months, although none of these parameters were correlated
      with age during the period studied.This anatomic study based on computed
      tomographic scan information may be useful for clinical application of the
      truncal maxillary nerve block in infants using the suprazygomatic route.

PMID- 19165033
TI  - Vulnerable structures during intraoral sagittal split ramus osteotomy.
AB  - The aim of this study was to elucidate the anatomical structures that are
      vulnerable to injury during sagittal split ramus osteotomy (SSRO). Twenty-nine
      hemifaces of 19 Korean adult cadavers (11 men and 8 women; age range, 50-91
      years) were dissected, and the locations of the facial nerve, retromandibular
      vein (RMV), and external carotid artery (ECA) were measured on the base of the
      mandibular posterior border and occlusal plane. Sagittal split ramus osteotomy
      was performed on the cadaver heads at intervals of 10 mm, and the proximity of
      the facial nerve was observed. The buccal branch and mandibular branch crossed
      the posterior border of the mandible (PBM). Most buccal branches (86%) crossed
      between 7/10 and 10/10 of the distance from gonion to mandibular notch (MN). Most
      mandibular branches (86%) were between 6/10 and 1/10 of the distance from gonion
      to MN. Most facial nerve trunks (FNTs) (82%) were within a circle of 9 mm in
      radius. Its center was located 34 mm posterior and 7 mm inferior to the MN. The
      FNT was located in the range of 11 to 14 mm medial to the PBM. The FNT emerged
      out of the stylomastoid foramen and ran anteroinferiorly in a direction of 45
      degrees. In 10-mm ramus setback osteotomy, FNT was very close to the PBM, running
      almost vertically. Retromandibular vein was 5.5 to 8.6 mm posterior and 4.2 to
      9.1 mm medial to the PBM. The ECA was located at 5.7 to 6.5 mm posterior and 10.5
      to 12.9 mm medial to PBM. Facial nerve could be averted from injury by doing less
      setback. Bleeding after SSRO is likely to be due to the injury of RMV which is
      closer to the PBM (4-9 mm) than ECA (12-13 mm).

PMID- 19165034
TI  - Unbiased estimation of the eyeball volume using the Cavalieri principle on
      computed tomography images.
AB  - The size of the eyeball has been the subject of a few studies. None of them used
      stereological methods to estimate the volume. In the current study, we estimated
      the volume of eyeball in normal men and women using the stereological methods.
      Eyeball volume (EV) was estimated using the Cavalieri principle as a combination
      of point-counting and planimetry techniques. We used computed tomography scans
      taken from 36 participants (15 men and 21 women) to estimate the EV. The mean
      (SD) EV values obtained by planimetry method were 7.49 (0.79) and 7.06 (0.85) cm
      in men and women, respectively. By using point-counting method, the mean (SD)
      values were 7.48 (0.85) and 7.21 (0.84) cm in men and women, respectively. There
      was no statistically significant difference between the findings from the 2
      methods (P > 0.05). A weak correlation was found between the axial length of
      eyeball and the EV estimated by point counting and planimetry (P < 0.05, r =
      0.494 and r = 0.523, respectively). The findings of the current study using the
      stereological methods could provide data for the evaluation of normal and
      pathologic volumes of the eyeball.

PMID- 19165035
TI  - Training model for microvascular anastomosis.
AB  - A cadaver model was used for microvascular training as nonviable biologic model.
      Twenty-four fixed and 2 fresh adult cadavers were used for microvascular
      training. The radial artery, ulnar artery, and cephalic vein of the forearm were
      preferred. Respectively, end-to-end, end-to-side, and end-on-side
      microanastomosis techniques were performed.A cadaver model has several advantages
      over other training models. There are numberless vessels to perform different
      techniques for microvascular anastomoses. Several students can simultaneously
      work on the same cadaver at the same time. In addition, there is the opportunity
      of working on vessels of different sizes and diameters.The same conditions on the
      cadaver can be created before operation, and effective presurgical microvascular
      practice can be performed. A free-flap dissection can be easily performed to get
      experience before clinical operations. Furthermore, it may be combined with live
      animal models.

PMID- 19165036
TI  - Temporomandibular joint ankylosis caused by chondroid hyperplasia from the callus
      of condylar neck fracture.
AB  - A patient who complained of difficulty in opening his mouth after condylar neck
      fracture 1 year ago presented typical features of temporomandibular joint
      ankylosis in clinical and radiologic examinations. To demonstrate a possible
      pathogenesis of temporomandibular joint ankylosis after condylar neck fracture,
      the fractured condylar portion removed was examined by histologic and
      immunohistochemical stainings. Interpositional gap arthroplasty was performed by
      removing the inferomesially displaced fractured condyle, and reconstruction with
      subcutaneous dermis to the previous vertical height was performed immediately.
      The fractured condylar portion was almost intact with slight erosion of the
      condylar cartilage. In the hematoxylin and eosin and Masson trichrome stainings,
      an extensive chondroid hyperplasia with abundant hyaline cartilage was shown in
      the removed condylar portion. There were also hyperplastic features of the
      synovial membrane, which were abnormally distributed throughout the chondroid
      tissues. In the immunohistochemical stainings of proliferating cell nuclear
      antigen (PCNA) and bone morphogenetic protein (BMP)-2 and BMP-4, the chondroid
      tissues were conspicuously hyperplastic and strongly positive for BMP-4 but
      sparse for BMP-2. From these results, we think that the hyperplastic chondroid
      tissue was derived from the callus of the primary fractured site of the condylar
      neck and propose that the chondroid tissue could proliferate continuously because
      of synovial tissue support from around the temporomandibular joint, resulting in
      temporomandibular joint ankylosis. This pathogenesis is quite different from
      those of other diaphyseal fracture of long bones.

PMID- 19165037
TI  - A triage system for referrals of pediatric skull deformities.
AB  - The clinical pathways for craniosynostosis and nonsynostotic skull deformity are
      entirely different. At the Dutch Craniofacial Center (DCFC), all patients were
      assessed in the same multidisciplinary craniofacial clinic, a common practice in
      countries with developed health care. However, the high volume of referrals of
      nonsynostotic cases frequently resulted in the capacity of these clinics being
      exceeded, with some patients being assessed in the general pediatric plastic
      surgery clinic instead. In these general clinics, not all the multidisciplinary
      team members are routinely present, so patients with craniosynostosis had to make
      a second journey for further assessment, causing inconvenience, expense, and
      potential delay in treatment. With triage at the community level unreliable and
      triage at clinic level inefficient, we decided to trial a triage system to
      increase efficiency and to ensure patients enter the correct clinical pathway
      earlier.The 2 craniofacial secretaries were issued with a flowchart to be
      completed for each new referral. The flowcharts were designed to triage the
      patients into true craniosynostosis with an appointment for the multidisciplinary
      clinic or nonsynostotic deformity with an appointment with the craniofacial nurse
      practitioner (CNP). During a 3-month period, 107 referrals were made. The triage
      category listed on the initial flowchart for each patient was compared, with the
      final diagnosis made in the multidisciplinary and CNP clinics.None of the
      patients triaged as nonsynostotic deformity on the flowcharts were found to be
      true craniosynostosis after clinical assessment by the CNP. Radiographic
      assessment or assessment by the craniofacial surgeons in the DCFC confirmed
      this.The flowchart questionnaire used at the DCFC is a highly sensitive and
      therefore safe method for detecting craniosynostosis. It has helped to improve
      efficiency by ensuring patients are seen in an appropriate setting.

PMID- 19165038
TI  - The helical arcade: anatomic basis for survival in near-total ear avulsion.
AB  - Survival of the ear based on a single vascular pedicle has been previously
      documented. The anatomic basis for this survival remains incompletely described.
      In the 3 clinical cases of inferior-to-superior near-total ear avulsion presented
      herein, the authors have observed that the ear can survive based on a narrow
      pedicle along the helical root. In an anatomic study to further investigate the
      relevant vascular anatomy, the common carotid artery system of 6 fresh human
      cadaver specimens was injected with latex. The superficial temporal artery and
      its branches located at the helical root were examined. This anatomic study
      showed that the upper auricular branch of the superficial temporal artery
      continues into the ear as the helical artery supplies an arterial arcade, which
      we have termed the helical arcade. This arcade seems to allow for communication
      between the anterior and posterior arterial systems of the ear and allows the
      helical artery to provide sufficient arterial supply to the entire ear.

PMID- 19165039
TI  - Survival after lip cancer diagnosis.
AB  - The purpose of this study was to analyze the 5-year survival rates of 82 patients
      with lip cancer attending 5 university hospitals during 1999-2003 in Tehran,
      Iran. We used information from patient records, telephone calls, and death
      register files of the Iran Ministry of Health to ascertain the patients' vital
      status. Associations between survival and the variables of sex, age, stage of the
      tumor at the time of diagnosis, treatment modality, and tumor histopathologic
      type were analyzed with Kaplan-Meier, log-rank, and Cox regression methods. Of
      all patients, 70 (85%) were men, with a median age of 62 years (mean, 58.6 years
      [SD, 15 years]; range, 27-85 years) at the time of diagnosis. The median follow
      up time of the patients was 57 months (mean, 56.4 months [SD, 28 months]; range,
      0-112 months). The 1- to 5-year overall survival rate was 91% to 62%. The tumor
      stage at the time of diagnosis and the treatment modality were associated with
      survival (P < 0.05) in both univariate and multivariable analyses. Patients who
      underwent surgery and had lower stage tumors at the time of diagnosis showed
      higher survival rates. No differences in patient survival were found regarding
      sex, age, and histopathologic type of tumors. These findings indicate that
      although lip tumors are curable, early detection, diagnosis, and treatment lead
      to even higher rates of survival. Importance of the early detection of lip cancer
      should be emphasized in all health care and cancer prevention campaigns directed
      to the public and professionals.

PMID- 19165040
TI  - Giant lymphangioma of the tongue.
AB  - This report presents the treatment of an extensive lymphatic malformation of the
      tongue. Sclerosing agents are now widely used as the first-line treatment of
      lymphatic malformation. However, treatment of lymphatic malformation involving
      the face and the vital structures such as the airway remains to be challenging. A
      4-year-old boy underwent a total of 15 OK-432 injection sclerotherapy treatments
      over a 2-year period, having slow progress until sudden enlargement of the tongue
      was noted shortly after the last injection. Partial excision of the lesion was
      performed. This case demonstrates the risk in treating large microcystic
      lymphatic malformation of the tongue with sclerotherapy and provides an insight
      in the management protocol.

PMID- 19165041
TI  - Carpenter syndrome.
AB  - Carpenter syndrome is a rare autosomal recessive disorder that belongs to a group
      of rare craniosynostosis syndromes (Bull Soc Med Paris 1906;23:1310). Carpenter
      syndrome is the rarest, with only occasional patients seen. There are 3 common
      features in all of these syndromes: craniosynostosis (skull base abnormalities,
      with early fusion in different sutures), midface hypoplasia, and musculoskeletal
      abnormalities. Clinical features of Carpenter syndrome include peculiar facies,
      asymmetry of the skull, polydactyly, brachymesophalangy, mild soft tissue
      syndactyly, obesity, hypogenitalism, congenital heart disease, and mental
      retardation (J Pediatr 1966;69:1; Am J Roentgenol 1969;106). The brachycephaly is
      caused by early fusion in the coronal, sagittal, and lambdoidal sutures (Proc R
      Soc Med Sect Study Dis Child 1909). Most of the affected patients have a surgical
      procedure between 3 to 9 months of age to open the cranial vault to make space
      for the brain to grow (Plast Reconstr Surg 1978;62:335). We present a patient
      with Carpenter syndrome who is unusual in that she is an adult who has never had
      surgical intervention.

PMID- 19165042
TI  - Frontal bandeau reconstruction with a fibula flap in a patient with Freeman
      Sheldon syndrome.
AB  - A 29-year-old woman with Freeman-Sheldon syndrome had a history of recurrent
      frontal sinus infections for which she underwent a 1-stage frontal sinus
      obliteration and cranioplasty using a free fibula osteocutaneous flap. This case
      is unique in that a free fibula flap had never been used to obliterate the
      frontal sinus in a patient with Freeman-Sheldon syndrome, nor had it been
      harvested from a limb with a clubfoot.

PMID- 19165043
TI  - Combined treatment protocol for temporomandibular joint ankylosis: an observation
      on a clinical problem.
AB  - Various techniques have been defined for the treatment of temporomandibular joint
      ankylosis. However, in some cases, they are unsuccessful, resulting in continuing
      pain and limitation in interincisal distance after surgery. This report describes
      the case of a 32-year-old woman who has been experiencing temporomandibular joint
      ankylosis for a period of 8 years. Several surgical procedures failed. A
      treatment approach combining auricular cartilage interposition arthroplasty with
      postsurgical functional treatment using a spring activator is presented. Using
      this approach, pain settled and maximal interincisal distance was raised from 22
      to 35 mm after 4 months and remained stable for further 10 months.

PMID- 19165044
TI  - Multiple fractures involving the orbit and incidental finding of large fourth
      ventricular epidermoid.
AB  - Epidermoid tumors located in the fourth ventricle are exceedingly rare, and the
      patients usually present with headaches, vertigo, and/or disequilibrium. We
      discuss the management of orbital floor and lateral wall fracture in a patient
      who was also incidentally diagnosed to have a large fourth ventricular epidermoid
      cyst. Although because of their availability and ease of use many allografts have
      been described, when available, the use of similar membranous bone of equivalent
      thickness makes the bone graft ideally suited for reconstruction of the orbital
      floor.

PMID- 19165045
TI  - Reconstruction of complicated scalp defect via skin traction.
AB  - Management of an open wound is a problem frequently faced, with skin defects that
      cannot be closed primarily. Functional and aesthetic outcome could be improved if
      primary approximation of skin in these large defects were possible. Primary
      closure may be assisted using the viscoelastic properties of the skin. The
      viscoelastic properties of mechanical creep and stress relaxation in the skin
      were described more than 40 years ago. If skin is stretched with a constant
      force, it will expand with time as long as it is kept under tension, a phenomenon
      known as mechanical creep. In contrast, if the skin is stretched to a constant
      distance, it will expand and lead to a decrease in the force or tension on the
      skin with time, a phenomenon known as stress relaxation. We have recently applied
      these stretching properties to close the scalp because of a defect, which
      previously would have undergone pericranial flap and split-thickness graft.
      Because of the partial necrosis of the pericranial flap, skin grafting failed. In
      the second stage, we inserted only the wrist part of elastic latex gloves to the
      wound edges in full thickness. The skin margins were advanced slowly and gently.

PMID- 19165054
TI  - Anterior skull base fractures: extradural surgical approach.

PMID- 19165065
TI  - Cyberknife image-guided radiosurgery.

PMID- 19165066
TI  - Obliteration dynamics in cerebral arteriovenous malformations after cyberknife
      radiosurgery: quantification with sequential nidus volumetry and 3-tesla 3
      dimensional time-of-flight magnetic resonance angiography.
AB  - OBJECTIVE: To investigate the time-dependent obliteration of cerebral
      arteriovenous malformations (cAVM) after CyberKnife radiosurgery (CKRS) (Accuray,
      Inc., Sunnyvale, CA) by means of sequential 3-T, 3-dimensional (3D), time-of
      flight (TOF) magnetic resonance angiography (MRA), and volumetry of the
      arteriovenous malformation (AVM) nidus. METHODS: In this prospective study, 3D
      TOF MRA was performed on 20 patients with cAVMs treated by single-fraction CKRS.
      Three-dimensional TOF MRA was performed on a 3-T, 32-channel magnetic resonance
      scanner (Magnetom TIM Trio; Siemens Medical Solutions, Erlangen, Germany) with
      isotropic voxel size at a spatial resolution of 0.6 x 0.6 x 0.6 mm3. The time
      dependent relative decay of the transnidal blood flow evidenced by 3D TOF MRA was
      referred to as "obliteration dynamics." Volumetry of the nidus size was performed
      with OsiriX imaging software (OsiriX Foundation, Geneva, Switzerland). All
      patients had 3 to 4 follow-up examinations at 3- to 6-month intervals over a
      minimum follow-up period of 9 months. Subtotal obliteration was determined if the
      residual nidus volume was 5% or less of the initial nidus volume. Stata/IC
      software (Version 10.0; Stata Corp., College Station, TX) was used for
      statistical analysis and to identify potential factors of AVM obliteration.
      RESULTS: Regarding their clinical status, case history, and pretreatments, the
      participants of this study represent difficult-to-treat cAVM patients. The median
      nidus volume was 1.8 mL (range, 0.4-12.5 mL); the median minimum dose prescribed
      to the nidus was 22 Gy (range, 16-24 Gy) delivered to the 67% isodose line
      (range, 55-80%). CKRS was well tolerated, with complications in 2 patients. No
      further hemorrhages occurred after RS, except 1 small and clinically inapparent
      incident. The median follow-up period after RS was 25.0 months (range, 11.7-36.8
      months). After RS, a statistically significant obliteration was observed in all
      patients. However, the obliteration dynamics of the cAVMs showed a pronounced
      variability, with 2 types of post-therapeutic behavior identified. cAVMs of Group
      A showed a faster reduction of transnidal blood flow than cAVMs in Group B. The
      median time to subtotal obliteration was 23.8 months for all patients, 11.6
      months for patients in Group A, and 27.8 months for patients in Group B (P =
      0.05). Logistic regression analysis revealed dose homogeneity and the
      circumscribed isodose to be the only variables (P < 0.01) associated with the
      obliteration dynamics in this study. The cumulative complete angiographic
      obliteration rate was 67% (95% confidence interval, 32-95%) 2 years after RS.
      CONCLUSION: The use of sequential 3D TOF MRA at 3 T and nidus volumetry enables a
      noninvasive quantitative assessment of the dynamic obliteration process induced
      by CKRS in cAVMs. This method may be helpful to identify factors related to AVM
      obliteration after RS when larger patient cohorts become available.

PMID- 19165067
TI  - Introducing sitetrack: continuous patient motion monitoring during stereotactic
      radiotherapy for the head.
AB  - OBJECTIVE: Immobilization of the head during stereotactic radiotherapy (STR) has,
      until recently, been fundamental for ensuring accuracy. We developed a continuous
      motion monitoring system (SiteTrack) to detect and quantify head movement during
      CyberKnife (Accuray, Inc., Sunnyvale, CA) STR and Leksell (Elekta AB, Stockholm,
      Sweden) frame fixation. In this study, we present findings obtained during tests
      of SiteTrack. METHODS: SiteTrack is composed of a potentiometer with 4 encoders
      connected through 4 threads tied to the plastic buttons attached to the
      thermoplastic mask, in the case of CyberKnife, or by 3 threads directly connected
      to the Leksell frame. The accuracy of SiteTrack was studied with a phantom using
      the target localization system of the CyberKnife. During CyberKnife treatment,
      SiteTrack software sends an emergency stop signal (E-stop) if the patient moves
      beyond a limit. Seventy-three cases of CyberKnife STR and 7 cases of Leksell
      frame fixation were monitored. RESULTS: In the phantom study, regression analysis
      showed a significant correlation between SiteTrack and target localization system
      parameters. The expected root mean square position error at the moment of E-stop
      was 0.62 +/- 0.44 mm when the E-stop limit was set at +/-0.5 mm. Twenty-two (30%)
      of 73 patients kept still during CyberKnife treatment (<0.5 mm); 51 (70%) of 73
      patients moved more than 0.5 mm and, thus, caused E-stops. SiteTrack monitoring
      during frame fixation showed motion beyond +/-1 mm in 4 cases and +/-0.5 mm in 3
      other cases. CONCLUSION: Significant head movement can occur during CyberKnife
      treatment or fixation with a Leksell frame. SiteTrack may improve the accuracy of
      the CyberKnife as well as frame-based STR.

PMID- 19165068
TI  - Cyberknife radiosurgery for trigeminal schwannomas.
AB  - OBJECTIVE: Trigeminal schwannomas (TS) are benign tumors that are managed by
      surgical resection and/or stereotactic radiosurgery. Most radiosurgical series
      report results using the gamma knife. The CyberKnife (Accuray, Inc., Sunnyvale,
      CA) is a frameless, robotic stereotactic radiosurgical system. In this series, we
      report our experience using the CyberKnife in the treatment of TS. METHODS: We
      retrospectively reviewed the medical records and diagnostic imaging in 13
      consecutive patients with TS who were treated with the CyberKnife from 2003 to
      2007. Seven patients had a previous surgical resection. The mean tumor volume was
      6.3 mL (range, 0.39-19.98 mL), and the mean marginal dose was 18.5 Gy. Six of the
      tumors were treated in a single session. The mean clinical follow-up period was
      21.8 months (range, 7-53 months). RESULTS: In this series, the tumor control rate
      was 100%. The average reduction in tumor volume was 45% (range, 14-98%). A modest
      improvement in facial pain was noted in 4 of the 6 patients who presented with
      this symptom. One patient had improvement in facial numbness, and another had
      improvement in pretreatment headaches. One patient developed jaw weakness and
      facial dysesthesia, and another patient developed asymptomatic radiation
      necrosis. CONCLUSION: Although the length of follow-up is limited, we report our
      initial experience with CyberKnife treatment of TS. Our results demonstrate tumor
      control rates and clinical outcomes that parallel those of previous reports using
      gamma knife radiosurgery; however, long-term follow-up studies are needed.

PMID- 19165069
TI  - Hypofractionated CyberKnife radiosurgery for perichiasmatic pituitary adenomas:
      early results.
AB  - OBJECTIVE: Radiation therapy is recommended for pituitary tumors that are
      refractory to surgical and medical therapies. The efficacy of single-fraction
      radiosurgery is established for these lesions, but lesions within 3 mm of the
      optic pathway cannot be safely treated with doses higher than 8 to 10 Gy. We
      hypothesized that the optic nerve will tolerate 5 consecutive daily radiosurgery
      fractions of 500 cGy with effective tumor control. METHODS: We reviewed our first
      20 patients with recurrent or residual pituitary adenomas within 3 mm of the
      optic chiasm treated with the CyberKnife radiosurgery system (Accuray, Inc.,
      Sunnyvale, CA). Tumors were treated with a mean coverage of 97 +/- 2.2% (range,
      89.8-99.7%), a mean conformity index of 1.3 +/- 0.2 (range, 1.1-1.6), and a mean
      treatment isodose line of 74.5 +/- 6.6% (range, 60-86%). The primary end point
      was an interim analysis of visual preservation, and secondary end points were
      radiographic and endocrinological tumor control. RESULTS: The mean follow-up
      period for visual field testing was 26.6 +/- 10.5 months (range, 10.6-41 months).
      The vision of all 14 patients with intact preoperative vision remained intact. Of
      the 5 patients with impaired vision, 2 remained stable, and 3 improved. No
      patient's vision deteriorated. The mean radiographic follow-up was 29.3 +/- 8.6
      months (range, 10.2-40.5 months). On magnetic resonance imaging, 12 tumors were
      stable, 8 were smaller, and none enlarged. CONCLUSION: This preliminary study
      establishes that the optic nerve and chiasm tolerate CyberKnife hypofractionated
      radiosurgery of 5 x 500 cGy to perichiasmatic pituitary adenomas. Early data
      suggest that this dosing paradigm may achieve satisfactory radiographic and
      endocrinological tumor control for these challenging lesions, but longer follow
      up is necessary to confirm these results.

PMID- 19165070
TI  - Neurosurgery. Prefaces.

PMID- 19165071
TI  - Cyberknife for brain metastases of malignant melanoma and renal cell carcinoma.
AB  - OBJECTIVE: To evaluate the efficacy of CyberKnife (Accuray, Inc., Sunnyvale, CA)
      stereotactic radiosurgery (SRS) for patients with brain metastases of malignant
      melanoma and renal cell carcinoma. METHODS: We conducted a retrospective review
      of all patients treated by image-guided radiosurgery at our institution between
      March 1999 and December 2005. Sixty-two patients with 145 brain metastases of
      renal cell carcinoma or melanoma were identified. RESULTS: The median follow-up
      period was 10.5 months. Forty-four patients had malignant melanoma, and 18
      patients had renal cell carcinoma. The median age was 57 years, and patients were
      classified as recursive partitioning analysis Class 1 (6 patients), 2 (52
      patients) or 3 (4 patients). Thirty-three patients had been treated systemically
      with either chemotherapy or immunotherapy, and 33 patients were taking
      corticosteroids at the time of treatment. The mean tumor volume was 1.47 mL
      (range, 0.02-35.7 mL), and the mean prescribed dose was 20 Gy (range, 14-24 Gy).
      The median survival after SRS was 8.3 months. Actuarial survival at 6 and 12
      months was 57 and 37%, respectively. On multivariate analysis, Karnofsky
      Performance Scale score (P < 0.01) and previous immunotherapy/clinical trial (P =
      0.01) significantly affected overall survival. One-year intracranial progression
      free survival was 38%, and local control was 87%. Intracranial control was
      impacted by whole-brain radiotherapy (P = 0.01), previous chemotherapy (P =
      0.01), and control of the primary at the time of SRS (P = 0.02). Surgical
      resection had no effect on intracranial or local control. Radiographic evidence
      of radiation necrosis developed in 4 patients (6%). CONCLUSION: CyberKnife
      radiosurgery provided excellent local control with acceptable toxicity in
      patients with melanoma or renal cell brain metastases. Initial SRS alone appeared
      to be a reasonable option, as survival was dictated by systemic disease.

PMID- 19165072
TI  - Foraminal nerve sheath tumors: intermediate follow-up after cyberknife
      radiosurgery.
AB  - OBJECTIVE: To conduct a retrospective review of outcomes in 15 patients with 18
      foraminal tumors, including 17 benign peripheral nerve sheath tumors and 1
      malignant peripheral nerve sheath tumor, who underwent CyberKnife (Accuray, Inc.,
      Sunnyvale, CA) radiosurgery at Stanford University Medical Center from 1999 to
      2006. METHODS: Symptoms and findings, neurofibromatosis (NF) association,
      previous radiation, imaging, dosimetry, tumor volume, central necrosis, and the
      relation of these factors to outcomes were evaluated. RESULTS: Before treatment,
      1 asymptomatic patient had radiculopathic findings, 3 patients experienced local
      pain with intact neurological examinations, and 7 patients had radiculopathic
      complaints with intact (1 patient), radiculopathic (4 patients), or
      radiculomyelopathic examinations (2 patients). Five patients had myelopathic
      complaints and findings. Three patients had NF1-associated neurofibromas, 1
      patient with NF2 had a schwannoma, and 1 patient had a schwannomatosis-related
      lesion. Two likely radiation-induced lesions, a neurofibroma and a malignant
      peripheral nerve sheath tumor, were observed. Prescribed doses ranging from 16 to
      24 Gy, delivered in 1 to 3 fractions of 6 to 20 Gy, resulted in maximum tumor
      doses ranging from 20.9 to 30 Gy. Target volumes ranged from 1.36 to 16.9 mL.
      After radiosurgery, the asymptomatic case remained asymptomatic, and neurological
      findings improved. Thirteen of 15 symptomatic patients with (12 patients) or
      without (3 patients) neurological findings improved (3 cases after resection) or
      remained stable, and 2 patients worsened. Symptoms and examinations remained
      stable or improved in 8 (80%) of 10 patients with schwannomas and 3 (60%) of 5
      patients with neurofibromas. Tumor volumes decreased in 12 (67%) of 18 tumors and
      increased in 3 tumors. Tumor volumes decreased in 8 of 10 schwannomas and 3 of 7
      neurofibromas. Central necrosis developed in 8 (44%) of 18 tumors. CONCLUSION:
      CyberKnife radiosurgery resulted in pain relief and functional preservation in
      selected foraminal peripheral nerve sheath tumors and a malignant peripheral
      nerve sheath tumor. Symptomatic and neurological improvements were more
      noticeable with schwannomas. Myelopathic symptoms may necessitate surgical
      debulking before radiosurgery.

PMID- 19165073
TI  - Treatment of chordomas with CyberKnife: georgetown university experience and
      treatment recommendations.
AB  - OBJECTIVE: To determine the efficacy and safety of chordoma treatment with
      CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (CK/SRS).
      METHODS: Eighteen patients with chordoma were treated with CK/SRS as a primary
      adjuvant (17 patients) or the only treatment (1 patient). The series included 24
      lesions (28 treatments). The median age of the patients was 60 years (range, 24
      85 years). Forty-four percent of the tumors were located in the mobile spine, 39%
      inside the cranium, and 17% in the sacral region. The male-to-female ratio was
      1:1. The mean tumor volume was 128.0 mL (range, 12.0-457.3 mL), and the median
      dose of 35 Gy (range, 24.0-40.0 Gy) was delivered in 5 sessions. The median
      follow-up period was 46 months (range, 7-65 months). RESULTS: There were 3
      significant complications in patients with previous irradiation, including
      infection in the surgical/radiation site (2 patients) and decreased vision (1
      patient). Improvement in pain and quality of life did not reach statistical
      significance (alpha = 0.05). Seven patients experienced recurrence at a median of
      10 months (range, 5-38 months), and 4 patients with disseminated disease died 7
      to 48 months after therapy. Two patients had a partial response, whereas 9 others
      had stable disease. The local control rate at 65 months was 59.1%, with an
      overall survival of 74.3% and disease-specific survival of 88.9%. We estimated an
      alpha/beta ratio of 2.45 for chordomas, which supports hypofractionation.
      CONCLUSION: The CK/SRS safety and efficacy profile compares favorably with those
      of other treatment delivery systems. CK/SRS appears to reduce tumor volume, given
      an adequate dose. The authors recommend treatment with 40 Gy in 5 sessions to the
      clinical treatment volume, which includes the gross tumor volume and at least a 1
      cm margin.

PMID- 19165074
TI  - Stereotactic radiosurgery for the treatment of primary sarcomas and sarcoma
      metastases of the spine.
AB  - OBJECTIVE: Spinal sarcomas pose unique treatment dilemmas because of the
      difficulty of achieving adequate surgical margins and/or delivering curative
      radiation doses (65 Gy) in close proximity to the spinal cord. This study used
      hypofractionated stereotactic radiosurgery (SRS) to deliver higher biologically
      effective doses to treat primary spinal sarcomas and spinal sarcoma metastases.
      METHODS: Twenty-four patients with spinal or paraspinal sarcomas entered an
      Institutional Review Board-approved registry trial to evaluate SRS efficacy. They
      were assessed at regular intervals for pain control, disease progression, and
      complications for a minimum of 12 months or until death. RESULTS: The median
      treatment dose for the spinal sarcoma lesions was 30 Gy at the 80% isodose in 3
      fractions, with some variation based on tumor size, shape, and dose to adjacent
      critical structures. Seven patients were treated definitively; all had excellent
      pain relief and are alive with a mean follow-up period of 33 months. Two patients
      had complete tumor regression, 3 had partial regression, and 2 experienced
      recurrences and have been re-treated. Seven patients underwent resection and
      adjuvant SRS. One of 3 patients treated preoperatively had complete tumor
      regression, and none of the 4 patients treated postoperatively had a local
      recurrence with a mean follow-up period of 43.5 months. All 10 patients with
      sarcoma metastases to the spine (16 lesions) died, with a mean survival of 11.1
      months from first spinal metastasis treatment. Complete pain relief was achieved
      in 8 patients, partial relief in 7 patients, and none in 1 patient. No patient
      developed radiation myelitis. CONCLUSION: These preliminary results suggest that
      SRS may have a role in the definitive treatment of patients with primary spinal
      sarcomas who are deemed unresectable and as adjuvant treatment in those
      undergoing surgery and for palliation of sarcoma metastases.

PMID- 19165075
TI  - CyberKnife stereotactic radiotherapy for spinal tumors: value of computed
      tomographic myelography in spinal cord delineation.
AB  - OBJECTIVE: For para- and intraspinal tumors, precise spinal cord delineation is
      critical for CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiotherapy.
      We evaluated whether computed tomographic (CT) myelography is superior to
      magnetic resonance imaging (MRI) for accurate spinal cord delineation. Treatment
      parameters and short-term outcome and toxicity are also presented. METHODS: The
      planning CT scan, the gadolinium-enhanced, T1-weighted, 3-dimensional (3D) fast
      imaging employing steady-state acquisition MRI scan, and the CT myelogram were
      fused before volume-of-interest delineation. The planning target volume margin
      was less than 1 mm using the Xsight Spine tracking system (Accuray). We present
      data from 11 heavily pretreated patients who underwent CyberKnife stereotactic
      radiosurgery between November 2006 and January 2008. RESULTS: Spatial resolution
      was 0.46 and 0.93 mm/pixel for CT myelography and 3D-fast imaging employing
      steady-state acquisition MRI, respectively. The contrast between cerebrospinal
      fluid and spinal cord was excellent with CT myelography. A transient
      postmyelography headache occurred in 1 patient. The mean gross tumor volume was
      51.1 mL. The mean prescribed dose was 34 Gy in 4 fractions (range, 2-7 fractions)
      with 147 beams (range, 79-232 beams) to the 75% reference isodose line (range, 68
      80%), covering 95% (range, 86-99%) of the gross tumor volume with a mean
      conformity index of 1.4 (range, 1.1-1.8). No short-term toxicity on the spinal
      cord was noted at 1- to 6-months of follow-up. CONCLUSION: CT myelography was
      more accurate for spinal cord delineation than 3D-fast imaging employing steady
      state acquisition MRI (used for its myelographic effect), particularly in the
      presence of ferromagnetic artifacts in heavily pretreated patients or in patients
      with severe spinal compression. Because other MRI sequences (T2 and gadolinium
      enhanced T1) provide excellent tumor characterization, we suggest trimodality
      imaging for spinal tumor treatment to yield submillimetric delineation accuracy.
      Combined with CyberKnife technology, CT myelography can improve the feasibility
      of dose escalation or reirradiation of spinal tumors in selected patients,
      thereby increasing local control while avoiding myelopathy. Further follow-up and
      prospective studies are warranted.

PMID- 19165076
TI  - Delayed radiation-induced myelopathy after spinal radiosurgery.
AB  - OBJECTIVE: Spinal cord injury is arguably the most feared complication in
      radiotherapy and has historically limited the aggressiveness of spinal tumor
      treatment. We report a case series of 6 patients treated with radiosurgery who
      developed delayed myelopathy. METHODS: Between 1996 and 2005, 1075 patients with
      benign or malignant spinal tumors were treated by CyberKnife (Accuray, Inc.,
      Sunnyvale, CA) robotic radiosurgery at Stanford University Medical Center and the
      University of Pittsburgh Medical Center. Patients were followed prospectively
      with clinical and radiographic assessments at 1- to 6-month intervals. A
      retrospective review identified patients who developed delayed radiation-induced
      myelopathy. Six patients (5 women, 1 man) with a mean age of 48 years (range, 25
      61 years) developed delayed myelopathy at a mean of 6.3 months (range, 2-9
      months) after spinal radiosurgery. Three tumors were metastatic; 3 were benign.
      The metastases were in the upper to midthoracic spine, whereas the benign tumors
      were partially in the cervical region. Three cases involved previous radiation
      therapy. RESULTS: Dose volume histograms were generated for target and critical
      structures. Clinical and dosimetric factors were analyzed for factors predictive
      of spinal cord injury. Specific dosimetric factors contributing to this
      complication could not be identified, but one-half of the patients with
      myelopathy received spinal cord biological equivalent doses exceeding 8 Gy.
      CONCLUSION: Delayed myelopathy after radiosurgery is uncommon with the dose
      schedules used in this case series. Radiation injury to the spinal cord occurred
      over a spectrum of dose parameters that prevented identification of specific
      dosimetric factors contributing to this complication. Primarily, biological
      equivalent dose estimates were not usable for defining spinal cord tolerance to
      hypofractionated dose schedules. We recommend limiting the volume of spinal cord
      treated above an 8-Gy equivalent dose, because half of the complications occurred
      beyond this level.

PMID- 19165077
TI  - Cyberknife radiosurgery for benign meningiomas: short-term results in 199
      patients.
AB  - OBJECTIVE: To present initial, short-term results obtained with an image-guided
      radiosurgery apparatus (CyberKnife; Accuray, Inc., Sunnyvale, CA) in a series of
      199 benign intracranial meningiomas. METHODS: Selection criteria included lesions
      unsuitable for surgery and/or remnants after partial surgical removal. All
      patients were either symptomatic and/or harboring growing tumors. Ninety-nine
      tumors involved the cavernous sinus; 28 were in the posterior fossa, petrous
      bone, or clivus; and 29 were in contact with anterior optic pathways. Twenty-two
      tumors involved the convexity, and 21 involved the falx or tentorium. One hundred
      fourteen patients had undergone some kind of surgical removal before
      radiosurgery. Tumor volumes varied from 0.1 to 64 mL (mean, 7.5 mL) and radiation
      doses ranged from 12 to 25 Gy (mean, 18.5 Gy). Treatment isodoses varied from 70
      to 90%. In 150 patients with lesions larger than 8 mL and/or with tumors situated
      close to critical structures, the dose was delivered in 2 to 5 daily fractions.
      RESULTS: The follow-up periods ranged from 1 to 59 months (mean, 30 months;
      median, 30 months). The tumor volume decreased in 36 patients, was unchanged in
      148 patients, and increased in 7 patients. Three patients underwent repeated
      radiosurgery, and 4 underwent operations. One hundred fifty-four patients were
      clinically stable. In 30 patients, a significant improvement of clinical symptoms
      was obtained. In 7 patients, neurological deterioration was observed (new cranial
      deficits in 2, worsened diplopia in 2, visual field reduction in 2, and worsened
      headache in 2). CONCLUSION: The introduction of the CyberKnife extended the
      indication to 63 patients (>30%) who could not have been treated by single
      session radiosurgical techniques. The procedure proved to be safe. Clinical
      improvement seems to be more frequently observed with the CyberKnife than in our
      previous linear accelerator experience.

PMID- 19165078
TI  - Cost-utility analysis of the cyberknife system for metastatic spinal tumors.
AB  - OBJECTIVE: Using decision analysis, a cost-utility study evaluated the cost
      effectiveness of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic
      radiosurgery (SRS) in comparison to external beam radiation therapy in the
      treatment of metastatic spinal malignancies. METHODS: The published literature
      provided evidence on the effectiveness of the comparator interventions in the
      absence of primary outcomes data. Costs of care were derived from Centers for
      Medicare and Medicaid Services fee schedules. A Markov model was constructed from
      the payer perspective to simulate the outcomes of patients undergoing
      nonchemotherapeutic interventions for metastatic spinal tumors. Because cancer
      therapies bear significant health and economic consequences, the impact of
      treatment-related toxicities was integrated into the model. Given the terminal
      nature of these conditions and the limited life expectancy of the patient
      population, the time horizon for the analysis was limited to 12 months. RESULTS:
      Patients treated with CyberKnife SRS gained an additional net health benefit of
      0.08 quality-adjusted life year; the calculated cost of CyberKnife SRS was $1933
      less than external beam radiation therapy for comparable effectiveness. The
      incremental cost per benefit for this strategy ($41 500 per quality-adjusted life
      year) met payers' willingness-to-pay criteria. CONCLUSION: Cost-utility analysis
      demonstrated that CyberKnife SRS was a superior, cost-effective primary
      intervention for patients with metastatic spinal tumors compared with
      conventional external beam radiation therapy.

PMID- 19165079
TI  - Nonisocentric radiosurgical rhizotomy for trigeminal neuralgia.
AB  - OBJECTIVE: Although stereotactic radiosurgery is an established procedure for
      treating trigeminal neuralgia (TN), the likelihood of a prompt and durable
      complete response is not assured. Moreover, the incidence of facial numbness
      remains a challenge. To address these limitations, a new, more anatomic
      radiosurgical procedure was developed that uses the CyberKnife (Accuray, Inc.,
      Sunnyvale, CA) to lesion an elongated segment of the retrogasserian cisternal
      portion of the trigeminal sensory root. Because the initial experience with this
      approach resulted in an unacceptably high incidence of facial numbness, a gradual
      dose and volume de-escalation was performed over several years. In this single
      institution prospective study, we evaluated clinical outcomes in a group of TN
      patients who underwent lesioning with seemingly optimized nonisocentric
      radiosurgical parameters. METHODS: Forty-six patients with intractable idiopathic
      TN were treated between January 2005 and June 2007. Eligible patients were either
      poor surgical candidates or had failed previous microvascular decompression or
      destructive procedures. During a single radiosurgical session, a 6-mm segment of
      the affected nerve was treated with a mean marginal prescription dose of 58.3 Gy
      and a mean maximal dose of 73.5 Gy. Monthly neurosurgical follow-up was performed
      until the patient became pain-free. Longer-term follow-up was performed both in
      the clinic and over the telephone. Outcomes were graded as excellent (pain-free
      and off medication), good (>90% improvement while still on medication), fair (50
      90% improvement), or poor (no change or worse). Facial numbness was assessed
      using the Barrow Neurological Institute Facial Numbness Scale score. RESULTS:
      Symptoms disappeared completely in 39 patients (85%) after a mean latency of 5.2
      weeks. In most of these patients, pain relief began within the first week. TN
      recurred in a single patient after a pain-free interval of 7 months; all symptoms
      abated after a second radiosurgical procedure. Four additional patients underwent
      a repeat rhizotomy after failing to respond adequately to the first operation.
      After a mean follow-up period of 14.7 months, patient-reported outcomes were
      excellent in 33 patients (72%), good in 11 patients (24%), and poor/no
      improvement in 2 patients (4%). Significant ipsilateral facial numbness (Grade
      III on the Barrow Neurological Institute Scale) was reported in 7 patients (15%).
      CONCLUSION: Optimized nonisocentric CyberKnife parameters for TN treatment
      resulted in high rates of pain relief and a more acceptable incidence of facial
      numbness than reported previously. Longer follow-up periods will be required to
      establish whether or not the durability of symptom relief after lesioning an
      elongated segment of the trigeminal root is superior to isocentric radiosurgical
      rhizotomy.

PMID- 19165080
TI  - Cyberknife stereotactic radiosurgical rhizotomy for trigeminal neuralgia:
      anatomic and morphological considerations.
AB  - OBJECTIVE: To search for correlations between specific anatomic, geometric, and
      morphological properties of the trigeminal nerve and the success of radiosurgical
      treatment and elimination of facial hypesthesia as a complication. METHODS: Forty
      six patients with at least 6 months of follow-up after CyberKnife (Accuray, Inc.,
      Sunnyvale, CA) rhizotomy were retrospectively reviewed. Patients treated after
      2004 were entered into the study after congruity in treatment parameters was
      established. Anatomic variations regarding the length of each nerve segment and
      angle of trigeminal nerve takeoff from brainstem to Meckel's cave in the axial
      and sagittal planes were studied. Dose distribution to surrounding critical
      structures (brainstem and trigeminal ganglion) was measured. After spatial
      relationships of involved structures and dose distributions were recorded, their
      relationship to treatment success, failure, or complication (primarily facial
      numbness) was tabulated. RESULTS: Forty-five patients (97.2%) experienced pain
      relief immediately or within weeks. Thirty-four patients maintained excellent
      outcome. Some degree of facial numbness developed in 18 patients (39.1%) and was
      mild in 11 of them (Grade II on the Barrow Neurological Institute scale).
      Patients with a sagittal-angle trigeminal nerve takeoff from the brainstem in the
      range of 150 to 170 degrees measured from the horizontal plane had a more
      favorable outcome (P = 0.03) than patients with less obtuse relationships to the
      proximal nerve origin. Patients who received higher doses of radiation to the
      brainstem/dorsal root entry zone of the trigeminal nerve experienced a higher
      rate of posttreatment facial anesthesia. CONCLUSION: There may be important
      anatomic and geometric relationships between the treated trigeminal nerve and
      surrounding critical structures that warrant pretreatment target volume placement
      and dose distribution considerations.

PMID- 19165081
TI  - CyberKnife radiosurgery as a first treatment for idiopathic trigeminal neuralgia.
AB  - OBJECTIVE: To report the level of effectiveness and safety, in our experience, of
      CyberKnife (Accuray, Inc., Sunnyvale, CA) robotic radiosurgery as a first-line
      treatment against pharmacologically refractory trigeminal neuralgia. METHODS: We
      treated 33 patients with the frameless CyberKnife system as a monotherapy. The
      retrogasserian portion of the trigeminal nerve (a length of 4 mm, 2-3 mm anterior
      to the root entry zone) was targeted. Doses of 55 to 75 Gy were prescribed to the
      100% isodose line, according to a dose escalation protocol. The patients were
      evaluated for the level of pain control, time to pain relief, hypesthesia, and
      time to pain recurrence. RESULTS: The median age was 74 years. All but 2 patients
      (94%) achieved a successful treatment outcome. The follow-up period was 9 to 37
      months (mean, 23 months). The Barrow Neurological Institute Pain Intensity Scale
      (BPS) score before radiosurgery was III in 2 patients (6%), IV in 8 patients
      (24%), and V in 23 patients (70%). The time to pain relief was 1 to 180 days
      (median, 30 days). No facial numbness was observed. Only 1 patient developed a
      transitory dysesthesia of the tongue. After treatment, the BPS score was I, II,
      or III in 31 patients (97%). Pain recurred in 33% (11 patients) at a mean of 9
      months (range, 1-43 months). Three patients with recurrences had low pain control
      by medication (BPS score, IV), and 1 patient (BPS score, V) needed a
      radiofrequency lesioning (BPS score, I at 12 months). CONCLUSION: CyberKnife
      radiosurgery for trigeminal neuralgia allows pain relief at safe doses and is
      suggested for pharmacologically refractory trigeminal neuralgia. Higher
      prescribed doses were not associated with improvement in pain relief or
      recurrence rate.

PMID- 19165082
TI  - A note of caution on yellow fever vaccination during maraviroc treatment: a
      hypothesis on a potential dangerous interaction.

PMID- 19165083
TI  - Dynamic patterns of human immunodeficiency virus type 1 integrase gene evolution
      in patients failing raltegravir-based salvage therapies.
AB  - OBJECTIVE: : Evaluate HIV-1 subtype B integrase gene evolution in patients
      failing raltegravir (RAL)-based savage regimens by clonal analysis of the
      replicating viral quasispecies. DESIGN: : Seven triple class failure HIV-1
      (subtype B)-infected patients, followed at San Raffaele Hospital and enrolled in
      the RAL Expanded Access Program (MK0518-023), were evaluated. Patients were
      followed up for 24-48 weeks and due to the absence of other active drugs, RAL was
      maintained in their regimens even if resistance mutations were detected. METHODS:
      : Immunologic and virologic parameters were recorded every 4 weeks, and
      amplification and clonal analysis of viral populations were performed at baseline
      and every 4-12 weeks in all patients. RESULTS: : Resistance to RAL appeared
      initially associated with selection of single variants (Y143R, Q148R N155H) in
      the majority of patients; however, in three patients, complex patterns of viral
      mutations were observed. The clonal analysis of viral quasispecies allowed to
      describe the evolution of each viral population and the progressive accumulation
      of RAL resistance-associated mutations and polymorphisms associated with therapy
      failure. CONCLUSION: : The complex patterns of resistance mutations observed,
      including novel variants evolved under continuous RAL pressure, suggesting that
      they are the result of the equilibrium between drug resistance and enzyme
      function. Despite the efficacy of this compound, our data discourage its use in a
      functional monotherapy and maintaining RAL even in presence of RAL resistance
      associated mutations may lead to the progressive formation of viral reservoirs
      with multiple integrase inhibitor-resistant variants that may limit the future
      efficacy of other integrase inhibitors due to cross-resistance.

PMID- 19165085
TI  - Adefovir dipivoxil-induced acute tubular necrosis and Fanconi syndrome in a renal
      transplant patient.

PMID- 19165084
TI  - Protease inhibitor levels in hair strongly predict virologic response to
      treatment.
AB  - OBJECTIVE: Antiretroviral (ARV) therapies fail when behavioral or biologic
      factors lead to inadequate medication exposure. The currently available methods
      to assess ARV exposure are limited. Levels of ARVs in hair reflect plasma
      concentrations over weeks to months, and may provide a novel method for
      predicting therapeutic responses. DESIGN/METHODS: The Women's Interagency HIV
      Study, a prospective cohort of HIV-infected women, provided the basis for
      developing and assessing methods to measure commonly prescribed protease
      inhibitors (lopinavir/ritonavir and atazanavir) in small hair samples. We
      examined the association between hair protease inhibitor levels and initial
      virologic responses to therapy in multivariate logistic regression models.
      RESULTS: ARV concentrations in hair were strongly and independently associated
      with treatment response for 224 women starting a new protease inhibitor-based
      regimen. For participants initiating lopinavir/ritonavir, the odds ratio (OR) for
      virologic suppression was 39.8 [95% confidence interval (CI) = 2.8-564] for those
      with lopinavir hair levels in the top tertile (>1.9 ng/mg) compared to the bottom
      (</=0.41 ng/mg) when controlling for self-reported adherence, age, race, starting
      viral load and CD4 cell count, and prior experience with protease inhibitors. For
      women starting atazanavir, the adjusted OR for virologic success was 7.7 (95% CI
      = 2.0-29.7) for those with hair concentrations in the top tertile (>3.4 ng/mg)
      compared to the lowest (</=1.2 ng/mg). CONCLUSION: Protease inhibitor levels in
      small hair samples were the strongest independent predictor of virologic success
      in a diverse group of HIV-infected adults. This non-invasive method for
      determining ARV exposure may have particular relevance for the epidemic in
      resource-poor settings due to the ease of collecting and storing hair.

PMID- 19165086
TI  - Disco funerals: a risk situation for HIV infection among youth in Kisumu, Kenya.
AB  - OBJECTIVE: We investigated the so-called 'disco funeral' phenomenon in Kisumu,
      Kenya, whereby community members including adolescents congregate at the home of
      the deceased for several days, accompanied by music and dancing. We explored
      whether disco funerals are a risk situation for HIV/sexually transmitted
      infection infection among youth. DESIGN: : Cross-sectional qualitative study.
      METHODS: We conducted 44 in-depth interviews with male and female adolescents
      aged 15-20 years in Kisumu municipality in Nyanza Province, Kenya. We also made
      observations during six disco funerals. RESULTS: Disco funerals were an important
      place for young people to hang out; they increased the opportunities to meet and
      engage in (risky) sexual activities. Many adolescents reported having casual sex
      on these occasions, sometimes with multiple partners, and mostly without condoms.
      Some girls were forced into sex, and there were several accounts of gang rape.
      Sex in exchange for money was reported frequently. Drugs and alcohol seemed to
      facilitate unprotected, multiple-partner, coerced, and transactional sex.
      CONCLUSION: In Kisumu, a town with a generalized HIV/AIDS epidemic, the high AIDS
      mortality leads to frequent disco funerals. Because many adolescents are having
      unprotected, transactional, or coerced sex at these occasions, disco funerals
      might contribute to the high HIV prevalence among youth, especially among
      adolescent girls. HIV interventions urgently need to include outreach actions to
      youth who hang out at disco funerals and link up with parents and funeral
      organizers to reduce risk situations.

PMID- 19165087
TI  - Should biomarker estimates of HIV incidence be adjusted?
AB  - OBJECTIVE: To evaluate adjustment procedures that have been proposed to correct
      HIV incidence rates derived from cross-sectional surveys of biomarkers (e.g. BED
      capture enzyme immunoassay). These procedures were motivated by some reports that
      the biomarker BED approach overestimates incidence when compared to cohort
      studies. DESIGN: Consideration of the Hargrove and McDougal adjustment procedures
      that adjust biomarker estimates of HIV incidence rates for misclassification with
      respect to the timing of infections. METHODS: : Performed mathematical and
      statistical analysis of the adjustment formulas. Evaluated sources of error in
      cohort studies of incidence that could also explain discrepancies between cohort
      and biomarker estimates. RESULTS: The McDougal adjustment has no net effect on
      the estimate of HIV incidence because false positives exactly counterbalance
      false negatives. The Hargrove adjustment has a mathematical error that can cause
      significant underestimation of HIV incidence rates, especially if there is a
      large pool of prevalent long-standing infections. CONCLUSION: The two adjustment
      procedures of biomarker incidence estimates evaluated here that purport to
      correct for misclassification do not increase accuracy and in some situations can
      introduce significant bias. Instead, the accuracy of biomarker estimates can be
      increased through improvements in the estimates of the mean window period of the
      populations under study and the representativeness of the cross-sectional
      samples. Cohort estimates of incidence are also subject to important sources of
      error and should not blindly be considered the gold standard for assessing the
      validity of biomarker estimates.

PMID- 19165088
TI  - Antiretroviral therapy and congenital abnormalities in infants born to HIV
      infected women in the UK and Ireland, 1990-2007.
AB  - OBJECTIVE: To explore the rate of reported congenital abnormalities in infants
      exposed to antiretroviral therapy in utero. DESIGN: Comprehensive national
      surveillance study in the UK and Ireland. METHODS: Births to diagnosed HIV
      infected women are reported to the National Study of HIV in Pregnancy and
      Childhood. Infants born between 1990 and 2007 were included. RESULTS: The rate of
      reported major and minor congenital abnormality was 2.8% (232/8242) overall, and
      there was no significant difference by timing of ART exposure: 2.8% (14/498) in
      unexposed infants, 2.7% (147/5427) following second or third trimester exposure,
      and 3.1% (53/1708) following first trimester exposure (P = 0.690). There was no
      difference in abnormality rates by class of ART exposure in the first trimester
      (P = 0.363), and no category of abnormality was significantly associated with
      timing of ART, although numbers in these groups were small. There was no
      increased risk of abnormalities in infants exposed to efavirenz (P = 0.672) or
      didanosine (P = 0.816) in the first trimester. CONCLUSION: These findings, based
      on a large, national, unselected population provide further reassurance that ART
      in utero does not pose a major risk of fetal anomaly.

PMID- 19165089
TI  - Relationship between cardiac rehabilitation and survival after acute cardiac
      hospitalization within a universal health care system.
AB  - BACKGROUND: The magnitude and mechanisms of survival benefit associated with
      cardiac rehabilitation services among real-world populations within a universal
      health care system remain unclear. METHODS: This retrospective matched cohort
      study compared the long-term survival of 2042 cardiac rehabilitation participants
      with 2042 matched controls after an index acute cardiac hospitalization between
      1999 and 2003, in Ontario, Canada. Each patient survived at least 1 year without
      recurrent admissions after discharge from the index hospitalization, and was
      followed for a mean of 5.25 years. Additional matching criteria included the type
      of sentinel cardiac events, age, sex, socioeconomic status, geography, previous
      cardiac and noncardiac hospitalizations. A Cox proportional hazards model further
      adjusted for baseline cardiovascular risk factors and process factors,
      cardiovascular risk-factor progression, downstream coronary procedure and
      evidence-based pharmacotherapy utilization. RESULTS: Cardiac rehabilitation
      participation was associated with a 50% lower mortality rate (2.6 vs. 5.1%,
      P<0.001) as compared with population-matched controls. Statistically significant
      mortality benefits were observed among high-risk patients, and there was no
      significant interaction among age, cardiac rehabilitation participation, and
      survival (P=0.22). Associated survival advantages were not meaningfully altered
      after adjustment for cardiovascular risk-factor progression or the downstream
      utilization rates of cardiac procedures and evidence-based cardiovascular
      therapies; survival benefits predominantly applied to those patients that were
      most compliant with the program. CONCLUSION: Cardiac rehabilitation is associated
      with significant long-term survival advantages after index cardiovascular
      hospitalizations. Despite universal access to medical care, such survival
      advantages seem to be mediated by compliant behaviors more so than by ancillary
      health service or evidence-based pharmacotherapy utilization.

PMID- 19165090
TI  - Particulate air pollution, coronary heart disease and individual risk assessment:
      a general overview.
AB  - Both long-term and short-term exposure to air pollution is associated with a
      marked increase in cardiovascular morbidity and mortality because of the coronary
      syndrome and its complications. The exact molecular mechanism that is responsible
      for these acute and chronic effects is not elucidated yet. Potential
      pathophysiological pathways, however, include vascular dysfunction, inflammation,
      and oxidative stress and altered cardiac autonomic dysfunction. Actually, the
      cardiovascular risk assessment for individual patients with regard to air
      pollution is still complicated. To support decision-making in clinic, we propose
      a risk model, named 'CardioVascular and AIR pollution' risk table, composed of
      acknowledged factors in the relationship of cardiovascular disease and air
      pollution.

PMID- 19165091
TI  - A novel TGF-beta antagonist speeds reepithelialization and reduces scarring of
      partial thickness porcine burns.
AB  - Scar formation after thermal injury is common and results in significant
      aesthetic and functional impairment. Transforming growth factor beta (TGF-beta)
      plays a significant role in scar formation. We tested the hypothesis that a novel
      TGF-beta peptantagonist would reduce scar formation and wound contraction in
      partial thickness burns by using a randomized controlled experiment. The subjects
      include two domestic pigs (20-25 kg). Forty burns were created on the animal's
      dorsum using an aluminum bar preheated to 80 degrees C and applied for 20 seconds
      resulting in a partial thickness thermal burn extending half way down the dermis.
      Burns were treated every other day for 1 week, then twice weekly for 3 weeks with
      a topical TGF-beta antagonist or its vehicle. Full thickness biopsies were
      obtained from all burns at 7, 10, and 14 days after injury. The wounds were
      completely excised after 28 days for histological assessment. Wound sections were
      stained with H&&E and evaluated by a dermatopathologist masked to treatment
      assignment for reepithelialization and depth of scar formation. We also
      determined the number of wounds at 28 days that healed with contracted, hour
      glass shaped scars. Data were compared with chi and t-tests. Twenty burns were
      treated with TGF-beta antagonist and 20 with control vehicle. TGF-beta antagonist
      increased the percentage of completely reepithelialized wounds at 14 days (90 vs
      45%, P = .002) and reduced the percentage of contracted wounds (35 vs 65%, P =
      .02) and full thickness scars (10 vs 60%, P = .002) at 28 days. Treatment of
      partial thickness porcine burns with the TGF-beta antagonist speeds
      reepithelialization and reduces scar formation and wound contraction in partial
      thickness porcine burns.

PMID- 19165092
TI  - Is length of stay linearly related to burn size? A glimmer from the national burn
      repository.

PMID- 19165093
TI  - In vivo evaluation of histomorphological alterations in first-degree burn
      injuries by means of confocal-laser-scanning microscopy-more than "virtual
      histology?".
AB  - There are various approaches to the treatment of superficial burns. No modality
      exists to date for determining treatment efficiency on morphological features. We
      review the first application of high-resolution in vivo confocal-laser-scanning
      microscopy (CLSM) to the evaluation of superficial burns on a histomorphological
      level. Sixteen patients (6 women, 10 men; 34.5 +/- 16.2 years) with first-degree
      thermal contact injuries to a maximum extent of 1% of the body surface were
      enrolled into the study. CLSM was performed with the Vivascope 1500 (Lucid Inc.,
      Rochester, NY) 24 hours after injury. The following parameters were assessed:
      cell size of the granular layer, thickness of the basal layer, minimal thickness
      of the epidermis, and diameter of capillary loops. Compared with the control
      sites 24 hours postburn, the minimal thickness of the epidermis increased on
      average by approximately 11% (P = .01; t-test); the thickness of the basal layer
      increased about 7% (P = .008; t-test); the diameter of capillary loops increased
      approximately by 17% (P = 0.003; t-test); and the cell size of the granular layer
      increased about 8% (P = .009; Wilcoxon's test). In vivo CLSM allows
      characterizing and quantifying histomorphological alterations in superficial
      burns. CLSM could be helpful in assessing the effects of various treatment
      approaches for superficial burns on a histomorphological level.

PMID- 19165095
TI  - Frostbite burns caused by liquid oxygen.
AB  - Frostbite burns are uncommon and they have various etiologies. We will present a
      case of rapid frostbite burn caused by liquid oxygen. The patient injured both
      hands from contact with liquid oxygen. The circumstances of this injury and
      preventive measures are discussed in this case report.

PMID- 19165096
TI  - Burn wound infection in a porcine burn model.

PMID- 19165097
TI  - Active burn rehabilitation starts at time of injury: an Australian perspective.

PMID- 19165098
TI  - A wound caused by a small alkaline cell (button battery) under a plaster cast:
      report of a case.
AB  - This is a case report of only the second known instance of an alkaline cell
      (button battery) causing a wound under a plaster cast.

PMID- 19165099
TI  - Repair severe burns of penis caused by excessive short-wave diathermy with
      scrotal flap.

PMID- 19165100
TI  - Fluoroscopic radiation burn after embolization of a spinal arteriovenous
      malformation.
AB  - Fluoroscopic radiation burns are being reported with increasing frequency because
      of the rise in number and duration of procedures performed under fluoroscopic
      guidance. We report a fluoroscopic radiation burn to a patient's back after three
      separate attempts to embolize a symptomatic spinal arteriovenous malformation,
      requiring fasciocutaneous flaps to ultimately close the wound. Risk factors,
      physiology, and modifications to decrease fluoroscopic radiation burns are
      discussed.

PMID- 19165101
TI  - Repair of complex abdominal wall defects from high-voltage electric injury with
      two layers of acellular dermal matrix: a case report.
AB  - High-voltage electric burn causing full-thickness necrosis of the abdominal wall
      and exposure of visceral organs is a real clinical challenge. This article
      reports a case of high-voltage electric burn causing a giant full-thickness
      abdominal wall defect. Seeing that it was unable to repair the abdominal wall
      defect with the conventional method, we used two layers of allogenic acellular
      dermal matrix substitutes to reconstruct and repair the defected abdominal wall.
      A 1-year follow-up showed that the abdominal wall of the patient recovered strong
      tenacity and strength without the evidence of significant complications.

PMID- 19165102
TI  - Silver absorption on burns after the application of Acticoat: data from pediatric
      patients and a porcine burn model.
AB  - Silver dressings have been widely used to successfully prevent burn wound
      infection and sepsis. However, a few case studies have reported the functional
      abnormality and failure of vital organs, possibly caused by silver deposits. The
      aim of this study was to investigate the serum silver level in the pediatric burn
      population and also in several internal organs in a porcine burn model after the
      application of Acticoat. A total of 125 blood samples were collected from 46
      pediatric burn patients. Thirty-six patients with a mean of 13.4% TBSA burns had
      a mean peak serum silver level of 114 microg/L, whereas 10 patients with a mean
      of 1.85% TBSA burns had an undetectable level of silver (<5.4 microg/L). Overall,
      serum silver levels were closely related to burn sizes. However, the highest
      serum silver was 735 microg/L in a 15-month-old toddler with 10% TBSA burns and
      the second highest was 367 microg/L in a 3-year old with 28% TBSA burns. In a
      porcine model with 2% TBSA burns, the mean peak silver level was 38 microg/L at 2
      to 3 weeks after application of Acticoat and was then significantly reduced to an
      almost undetectable level at 6 weeks. Of a total of four pigs, silver was
      detected in all four livers (1.413 microg/g) and all four hearts (0.342
      microg/g), three of four kidneys (1.113 microg/g), and two of four brains (0.402
      microg/g). This result demonstrated that although variable, the level of serum
      silver was positively associated with the size of burns, and significant amounts
      of silver were deposited in internal organs in pigs with only 2% TBSA burns,
      after application of Acticoat.

PMID- 19165103
TI  - Protective effects of free radical scavenger edaravone against xanthine oxidase
      mediated permeability increases in human intestinal epithelial cell monolayer.
AB  - The barrier function of the intestinal mucosa can be disturbed under a variety of
      pathologic insults. Reactive oxygen species play an important role in intestinal
      mucosal injury. This in vitro study examines the hypothesis that a free radical
      scavenger, edaravone (ED), ameliorates gut epithelial permeability increase
      caused by xanthine oxidase (XO)-mediated oxidative stress in a cell monolayer
      model. Human intestinal epithelial (HIE) cells were grown as monolayer in
      bicameral chambers. Twenty milliunits per milliliter of XO+0.25 mM of xanthine
      (XO+X group) or saline (control) were administered into the basal chambers.
      Another set of chambers was treated with XO+X and 0.6 mg/ml of ED (XO+X+ED
      group). The permeability was assessed by quantifying the transepithelial passage
      of fluorescence in isothiocyanate-labeled dextran. In another series of
      experiments, Escherichia coli C-25 was also applied in an apical chamber to
      evaluate the bacterial translocation through the monolayer. The concentration of
      the fluorescence in isothiocyanate-labeled dextran in the basal chamber of the
      control group was significantly higher than the control (705 +/- 50.2 vs 155 +/-
      45.4 mg/dl, P < .01). Treatment with ED prevented this permeability increase
      induced by the oxidative stress (P < .01). The incidence of bacterial
      translocation through the HIE monolayer in XO+X group was also higher than that
      of the control group (75 vs 13%, P < .05). Increased HIE cell monolayer
      permeability mediated by xanthine and XO was significantly attenuated with ED.
      This synthesized radical scavenger may have potential clinical applications
      against gut mucosal barrier dysfunction.

PMID- 19165104
TI  - Influence of comorbidities and age on outcome following burn injury in older
      adults.
AB  - Despite advances in medical and surgical techniques, older adults tend to be at
      high risk for adverse outcomes following burn injury. The purpose of this study
      was to examine the relative impacts of age and medical comorbidities on outcome
      following injury in a cohort of older adults. This was a retrospective study of
      all patients age 55 and over admitted to the University of Washington Burn Center
      from 1999 to 2003. To examine the effect of baseline medical comorbidities on
      outcome, a Charlson Comorbidity Index score was calculated for each patient.
      Multivariate regression analyses were used to examine the impact of age and
      comorbidities on mortality and other complications. Patient records were also
      matched with the National Death Index to determine the effects of age and
      comorbidities on mortality within 1 year following hospital discharge. A total of
      325 patients who were of 55 years and older were admitted to the burn center
      during the 5-year study period. The overall mortality rate was 18.5%. Mortality
      was independently associated with age, inhalation injury, and burn size. One-year
      mortality was significantly associated with those older than age 75 and the
      Charlson score. Longer length of stay was significantly associated with burn
      size, inhalation injury, and total number of in-hospital complications. This
      study demonstrates that patient age-independent of baseline medical comorbidities
      and TBSA burn are the most significant factors impacting in-hospital mortality
      risk following burn injury. Higher number of medical comorbidities was associated
      with increased mortality risk within 1 year following discharge.

PMID- 19165105
TI  - Key questions in ventilator management of the burn-injured patient (second of two
      parts).

PMID- 19165107
TI  - Invited Critique of "Efficacy of Naltrexone in the Treatment of Chronic
      Refractory Itching in Burn Patients: Preliminary Report of an Open Trial"

PMID- 19165108
TI  - The beneficial effects of plasma exchange after severe burn injury.
AB  - Severe burn injury results in a systemic inflammatory response that leads to
      increased capillary permeability and fluid leak into the interstitium. This
      global systemic capillary leak can be attributed, at least in part, to
      inflammatory mediators produced as a result of cellular injury. Plasma exchange
      has been used in the management of a number of illnesses with a significant
      inflammatory component, and, therefore, may have a role in the early management
      of burn injury. The purpose of this study was to review our institutional
      experience using plasma exchange in the management of severe burn injury. We
      performed a retrospective review of all patients receiving plasma exchange at our
      burn center between 2001 and 2005. Data collected included the following: burn
      size, presence of inhalation injury, resuscitation fluid received, urine output,
      lactate levels, base deficit levels, and hematocrit before and after the exchange
      procedure. A total of 37 patients underwent plasma exchange during the 5-year
      study period and seven patients underwent two plasma exchange treatments. Average
      TBSA burned was 48.6% (range 18-82) and 73% of patients sustained an inhalation
      injury. After plasma exchange, hourly fluid volume received significantly
      decreased (P < .05) and base deficit, lactate, and hematocrit levels
      significantly improved. Plasma exchange in the early resuscitation period was
      associated with decreased fluid administration, as well as increased urine output
      in the period during and immediately after the procedure. These data suggest that
      plasma exchange may provide a useful tool in the management of severe burn
      injury.

PMID- 19165109
TI  - Randomized clinical study of SilvaSorb gel in comparison to Silvadene silver
      sulfadiazine cream in the management of partial-thickness burns.
AB  - This prospective, randomized study assessed the clinical, microbiological, and
      patient comfort characteristics of two silver-based topical agents in the
      management of partial-thickness burn wounds. Pediatric patients were randomly
      assigned to treatment with either SilvaSorb Gel (Medline Industries, Munedelein,
      IL) or Silvadene silver sulfadiazine cream (King Pharmaceuticals, Bristol, TN)
      for up to 21 days or to the point of full reepithelialization of the wound.
      Inclusion criteria were patients ranging in age from 2 months to 18 years with
      TBSA ranging from 1 up to 40%. A total of 24 patients were enrolled and completed
      the study. Findings demonstrated that the use of SilvaSorb Gel was associated
      with less pain and greater patient satisfaction when compared with Silvadene. No
      statistically significant differences were found when assessing the rate of
      infection, time to reepithelialization, or the number of dressings changes
      required during treatment. The reduction of pain and improved overall patient
      satisfaction with the use of SilvaSorb Gel compared with Silvadene indicates an
      important role for SilvaSorb Gel in treatment of partial-thickness burns in a
      pediatric population.

PMID- 19165110
TI  - Pruritus in burns: review article.
AB  - Pruritus represents a common and distressing feature of burn wounds. Over the
      last decades, significant advances in neuroanatomical and neurophysiological
      knowledge have resulted in the elucidation of the mediators and pathways involved
      in the transmission of pruritic impulses. A plethora of therapeutic approaches
      have been evaluated mostly in small-scale studies involving burns patients
      targeting both the peripheral and the central components of the neurologic
      pathway. Antihistamines, doxepin, massage therapy, and transcutaneous electrical
      nerve stimulation are effective strategies to combat pruritus in burns patients.
      Recent studies have provided preliminary evidence regarding the effectiveness of
      gabapentin and ondansetron. The area of burns pruritus is under-researched and
      large-scale studies are required to reinforce the armamentarium of specialists
      with evidence-based regimens for the treatment of this highly distressing
      symptom.

PMID- 19165111
TI  - Adult burn patients with more than 60% TBSA involved-Meek and other techniques to
      overcome restricted skin harvest availability--the Viennese Concept.
AB  - Despite the fact that early excision and grafting has significantly improved
      outcome over the last decades, the management of severely burned adult patients
      with >/=60% total body surface area (% TBSA) burned still represents a
      challenging task for burn care specialists all over the world. In this article,
      we present our current treatment concept for this entity of severely burned
      patients and analyze its effect in a comparative cohort study. Surgical strategy
      comprised the use of split-thickness skin grafts (Meek, mesh) for permanent
      coverage, fluidized microsphere bead-beds for wound conditioning, temporary
      coverage (polyurethane sheets, Epigard; nanocrystalline silver dressings,
      Acticoat; synthetic copolymer sheets based on lactic acid, Suprathel; acellular
      bovine derived collagen matrices, Matriderm; allogeneic cultured keratinocyte
      sheets; and allogeneic split-thickness skin grafts), and negative-pressure wound
      therapy (vacuum-assisted closure). The autologous split-thickness skin graft
      expansion using the Meek technique for full-thickness burns and the delayed
      approach for treating dorsal burn wounds is discussed in detail. To demonstrate
      differences before and after the introduction of the Meek technique, we have
      compared patients of 2007 with >/=60% TBSA (n = 10) to those in a matched
      observation period (n = 7). In the first part of the comparative analysis, all
      patients of the two samples were analyzed with regard to age, abbreviated burn
      severity index, Baux, different entities of % TBSA, and survival. In the second
      step, only the survivors of both years were separated in two groups as follows:
      patients receiving skin grafts, using the Meek technique (n = 6), were compared
      with those without Meek grafting (n = 4). When comparing the severely burned
      patients of 2007 with a cohort of 2006, there were no differences for age (2007:
      46.4 +/- 13.4 vs. 2006: 39.1 +/- 14.8 years), abbreviated burn severity index
      score (2007: 12.2 +/- 1.0 vs. 2006: 12.1 +/- 1.2) or % TBSA (2007: 72.1 +/- 11.7
      vs. 2006: 69.3 +/- 8.7% TBSA). In these two rather small groups of severely
      burned patients with >/=60% TBSA, the overall survival rate of patients was 70.0%
      (7/10) in 2007 and 42.9% (3/7) in 2006, respectively. Almost all nonsurvivors in
      both years died within the first 5 days after admission. If assessing the
      different treatment modalities of the survivors, we found that although the Meek
      group patients were older (Meek 48.8 +/- 13.3 vs. non-Meek 26.8 +/- 11.5 years, P
      = .0381) and had consequently higher Baux scores (Meek 124.0 +/- 2.9 vs. non-Meek
      93.8 +/- 8.5, P = .0095) than the non-Meek patients, this seemed to have no
      effect on length-of-stay (80.5 +/- 9.7 vs. non-Meek 79.8 +/- 33.0 days), hospital
      length-of-stay (85.7 +/- 14.8 vs. non-meek 84.3 +/- 26.1 days) or number of
      operations (6.5 +/- 1.0 vs. non-Meek 7.0 +/- 4.1 operations). The achieved
      results represent a combination of various treatment changes and, therefore,
      cannot be attributed to a single modality. The Meek technique is one of the
      technical options to choose from, to achieve permanent skin replacement; we think
      that it has its place if integrated in a whole treatment concept for management
      of severely burned patients.

PMID- 19165112
TI  - Barriers impacting employment after burn injury.
AB  - This study investigates the barriers to return to work after burn injury. The
      electronic records of burn survivors treated at a Regional Burn Center outpatient
      clinic from 2001 to 2007 were retrospectively reviewed. Inclusion criteria
      included employment at the time of burn injury and age 18 years or older.
      Documentation of barriers to return to work were reviewed and classified into
      eight categories. Logistic regression analysis was used to determine predictors
      of return to work at more than 1 year. Ordered logistic regression analysis was
      performed to determine barrier predictors of employment. The authors identified
      197 patients for inclusion in the study. The age was 37 +/- 0.8 (mean +/- SEM)
      and total body surface area burned was 16 +/- 1.3%. Two thirds (n = 132) of
      subjects returned to work by 1 year. The most common barriers included pain (n =
      79), neurologic problems (n = 69), impaired mobility (n = 58), and psychiatric
      issues (n = 51). Pain was the most frequent barrier to return to work at all time
      intervals. Significant predictors of return to work at more than 12 months
      included length of hospital stay, inpatient rehabilitation, electric etiology,
      and burn at work (P < .05). Impaired mobility was a statistically significant (P
      < .05) barrier and other medical issues showed a trend toward statistical
      significance (P = .054) in predicting return to work at more than 12 months.
      There are many barriers that impede return to work in the burn population,
      including pain, neurologic problems, impaired mobility, and psychiatric issues.
      Early identification of those at risk for prolonged unemployment should prompt
      expeditious referral to comprehensive rehabilitation services that include work
      hardening and vocational training programs.

PMID- 19165113
TI  - A 12-year comparison of common therapeutic interventions in the burn unit.
AB  - Although most occupational and physical therapists in an acute burn care setting
      use similar therapy practices, the time frames at which these therapeutic
      interventions are carried out vary according to the burn centers' practices. The
      purpose of this survey was to investigate current trends in burn rehabilitation
      and compare the results with a similar survey performed in 1994. The survey was
      designed in a similar fashion to the 1994 survey to ascertain common trends in
      burn rehabilitation. The survey was sent to 100 randomly selected burn care
      facilities throughout the United States and Canada. Content included
      rehabilitation interventions, including evaluation, positioning, splinting,
      active range of motion, passive range of motion, ambulation, as well as the cross
      training of therapists. Significant increases in the percentages of burn centers
      initiating common therapy practices were found. Positioning (41% increase),
      active range of motion (48% increase), passive range of motion (52% increase),
      and ambulation (29% increase) were all found to have increases in the number of
      burn centers employing these practices in the same time frame. Overall comparison
      from 1994 to 2006 shows that common therapy techniques are being initiated
      earlier in the patient's acute burn stay. These results are consistent with
      recent medical trends of earlier acute discharges and more focus on outpatient
      rehabilitation.

PMID- 19165114
TI  - Validation of a Turkish version of the burn-specific health scale.
AB  - The abbreviated Burn-Specific Health Scale (BSHS) is an instrument that measures
      physical, mental, social, and general health in burn survivors. This scale is
      composed of 80 items. The aim of this study was to determine the reliability and
      validity of a Turkish version of the BSHS (the BSHS-Turkish). The BSHS
      abbreviated was translated and adapted for Turkish persons according to standard
      procedures. After a telephone interview with all eligible patients, the BSHS
      Turkish was mailed to 103 burn patients. Fifty-three patients (51.46%) filled out
      both questionnaires; the second one was completed within 15 days of the first
      one. The mean time that it took to complete the questionnaire was 31.06 +/- 15.2
      minutes (range, 3-60 minutes). The test-retest, internal reliability, and
      construct validity of the BSHS-Turkish were satisfactory according to intraclass
      correlation coefficient, Cronbach's alpha, and the Mann Whitney U test. The BSHS
      Turkish is a reliable and valid instrument for determining the health status of
      Turkish patients with burns.

PMID- 19165115
TI  - Efficacy of naltrexone in the treatment of chronic refractory itching in burn
      patients: preliminary report of an open trial.
AB  - Pruritus (itching) constitutes a source of severe distress for burn patients. The
      authors administered naltrexone to burn patients suffering from itching that was
      refractory to treatment with antihistamine and anticonvulsant medications to
      examine the efficacy of this medication as a treatment for pruritus in burn
      patients. Nineteen burn patients admitted to the Hallym Burn Center at Hangang
      Sacred Heart Hospital in Seoul, Korea, with burns over 40.32% (+/-18.3) of their
      total body surface were recruited for this study. The mean number of postburn
      days before naltrexone treatment was 157.3 days (+/-114.7). The authors observed
      a significant decrease in itching sensations after 2 weeks of treatment with
      naltrexone (z = -3.32, P = .001). Scratching activity was also decreased in 44.5%
      (+/-20.5) of subjects. The authors propose that naltrexone constitutes a
      potential antipruritic medication for burn patients suffering from treatment
      refractory itching.

PMID- 19165116
TI  - Influence of nebulized unfractionated heparin and N-acetylcysteine in acute lung
      injury after smoke inhalation injury.
AB  - To determine whether the combination of aerosolized unfractionated heparin and N
      acetylcystine reduces 28-days mortality and lung injury scores (LISs) in adult
      patients with smoke inhalation injury requiring mechanical ventilation. The study
      was a single-center retrospective study with historical control. The authors
      included 30 mechanically ventilated adult subjects who were admitted within 48
      hours of their bronchoscopy confirmed smoke inhalation injury over a 5-year
      period. The experimental group was treated with nebulized heparin sulfate, N
      acetylcystine, and albuterol sulfate. Controls received ventilation support and
      albuterol sulfate. The authors calculated acute physiology and chronic health
      evaluation (APACHE)-III scores on admission in addition to daily LIS for 7 days.
      The experimental group was divided into five APACHE-III subgroups and matched
      with inhalation lung injury patients in the historical control group. There was
      no significant difference in initial APACHE-III scores or LISs between groups
      (alpha = 0.05) upon entry to the study. The experimental group showed significant
      improvement in LISs, respiratory resistance and compliance measurements, and
      hypoxia scores as compared with controls throughout the duration of the study.
      There was a statistically significant survival benefit in the experimental group
      that was most pronounced in patients with APACHE-III scores >35. Survival for the
      control vs experimental group was 0.5714 +/- 0.1497 vs 0.9375 +/- 0.0605,
      respectively, (risk ratio -0.0055; 95% confidence interval -0.0314-0.0204; hazard
      ratio 1.003; number needed to treat 2.7). The use of aerosolized unfractionated
      heparin and N-acetylcystine attenuates lung injury and the progression of acute
      respiratory distress syndrome in ventilated adult patients with acute lung injury
      following smoke inhalation.

PMID- 19165117
TI  - Acute inflammation is persistent locally in burn wounds: a pivotal role for
      complement and C-reactive protein.
AB  - Severe burns can cause major complications, such as infection and deforming scar
      formation. Burn wounds induce an excessive inflammatory response. Serum levels of
      complement and the acute phase reactant C-reactive protein (CRP) are upregulated
      in response to burn injury and have been shown to be related to the severity of
      burn trauma and to the clinical outcome. However, complement and CRP have not
      been investigated on a tissue level locally at the site of the burn trauma.
      Protein levels and localization of complement activation product C3d and CRP were
      determined semi-quantitatively in burn eschar between 2 and 46 days after injury,
      using immunohistochemistry. CD68 and myeloperoxidase (MPO), markers for
      macrophages and neutrophilic granulocytes, respectively, were also analyzed on
      these biopsies. Skin biopsies of very recent surgical wounds (seconds old) served
      as controls. C3d and CRP are present at high levels in the burn wound. Protein
      levels of both mediators are significantly elevated up to at least 46 days after
      injury in comparison with control wounds. In line with this, neutrophils and
      macrophages infiltrate the burn wound in high numbers up to at least 46 days
      after injury. The excessive presence of the inflammatory mediators, complement
      and CRP, and the increased infiltration of neutrophils and macrophages in burn
      wounds up to 46 days after injury implicate a persistent ongoing acute
      inflammation locally in the burn wound up to weeks after the initial trauma.

PMID- 19165118
TI  - Assessment of functional limitation after necrotizing soft tissue infection.
AB  - Previous literature on necrotizing soft tissue infections (NSTIs) has focused on
      its diagnosis and high mortality, but to our knowledge, none have reported on the
      functional outcomes of patients surviving this devastating disease. The purpose
      of this study was to evaluate the management and assess factors associated with
      decreased physical function in patients who survived this life-threatening
      infection. A retrospective review was conducted on patients treated for NSTI in
      whom an evaluation of functional status was performed between 2002 and 2006.
      Measurements were based on the American Medical Association Guides of impairment
      rating, and categorized into a functional class from "minimal or no limitation"
      to "severe limitation." Multivariate analyses were performed to discern
      independent factors associated with functional limitation. Final disposition
      status after discharge was also recorded. A total of 297 patients were treated
      for NSTI during this time. Of these, 119 (41%) patients met inclusion criteria
      for review. Mean number of debridements and coverage procedures were 3.4 and 2.0,
      respectively. Although mean percent functional limitation was 7.1, which is
      classified as "minimal or no limitation," 30% of patients had "mild" to "severe"
      functional limitation. Extremity involvement was independently associated with a
      higher functional limitation class (P < .01). Functional limitation may challenge
      recovery from NSTI in many survivors. In this series, the involvement of an
      extremity predicted a higher functional limitation class at the time of
      discharge. Development of validated functional assessment tools and accurate
      longitudinal follow-up are necessary to measure the functional impact of NSTI.

PMID- 19165119
TI  - Transfusions in burn patients with/without comorbidities.
AB  - Medical comorbidities such as renal, cardiac, and cerebrovascular disease are
      known risk factors for mortality in burn patients. Patients with large burns
      often require blood transfusions during excision and skin grafting. The purpose
      of this study was to determine if there was a difference in the transfusion
      requirements of burn patients with/without comorbidities. This was a
      retrospective review of burn patient data between March 1999 and May 2004. There
      were 1,615 admissions to the burn unit; comorbidity data was available on 1,490
      patients. Of these, 383/1,490 (26%) had comorbid conditions upon admission:
      85/383 (22%) were transfused; 52/85 (61%) also underwent skin grafting. Most
      patients (298/383) with comorbidities were not transfused; however, 108/298 (36%)
      were grafted. Transfused patients with comorbidities had a mean +/- SD age of 53
      +/- 18 years old, a 19% +/- 22% TBSA burn, and a length of stay of 29 +/- 26 days
      compared with patients with comorbidities who did not require transfusion and
      were 48 +/- 19 years old, had 8 +/- 13% TBSA, and a length of stay of 8 +/- 8
      days. Of patients with comorbidities, 31/54 (57%) were transfused in the <10%
      TBSA group and 26/44 (59%) in the 10 to 19% TBSA group. There was a 5-fold
      increase in mortality among the transfused patients with comorbidities compared
      with the nontransfused group. Patients with comorbidities were more likely to be
      transfused in the <20% TBSA patient group. The odds of receiving a transfusion
      were highest in patients with cardiac diseases, stroke, and other central nervous
      system and psychiatric disorders. Co-occurring conditions that increased the odds
      of receiving a transfusion were procedures and inhalation with burn injury.

PMID- 19165121
TI  - Health state profiles and service utilization in community-living elderly.
AB  - BACKGROUND: We know that health status in older people is heterogeneous and that
      many need complex care. What is now required is a comprehensive description of
      this heterogeneity and the estimation of its effects on patterns of service
      utilization. OBJECTIVE: This study examines the possibility of classifying older
      people according to their complex health conditions and whether the way in which
      they consume services differs based on these classes. METHODS: We used latent
      class analysis to model heterogeneity and classify community living elderly into
      homogenous health state categories (ie, health profiles). The number of health
      profiles present in the sample was revealed using 17 health indicators collected
      at baseline in the demonstration project of SIPA (French acronym for System of
      Integrated Care for the frail elderly), a system of integrated care for frail
      older people (n = 1164). These profiles were then used in 2-part econometric
      models to study access and costs of several measures of services using data
      collected prospectively over the 22-months of the SIPA trial. RESULTS: We
      identified 4 substantially meaningful health profiles (prevalence: 23%, 11%, 36%,
      30%) characterized by differences along the physical, cognitive, and disability
      dimensions of health. Subsequent econometric modeling showed a differential
      effect of health profiles on use and costs along the continuum of health and
      social services. CONCLUSIONS: For older people with complex care needs,
      classification into homogeneous health subgroups unmasks differences in
      utilization patterns that can be used by decision makers in their attempt to
      improve the trajectory of care and adjust the distribution of resources to the
      needs of older people.

PMID- 19165120
TI  - Racial disparities in treatment preferences for rheumatoid arthritis.
AB  - BACKGROUND: Data suggest that differences in patient preferences may account for
      racial disparities in the use of medical interventions. Racial disparities have
      also been noted in outcomes and the delivery of healthcare services in chronic
      disease. Whether treatment preferences in chronic disease differ by race is not
      known. METHODS: We elicited treatment preferences for aggressive therapy in
      patients with rheumatoid arthritis who identified themselves as being black or
      white. RESULTS: One hundred fifty consecutive eligible patients were invited to
      participate. Of these, 136 subjects completed the interview. In unadjusted
      analysis, 51% of white participants preferred aggressive therapy compared with
      16% of blacks (P < 0.0001). Subjects who were married and reported having at
      least some college education had stronger preferences for aggressive therapy
      compared with their respective counterparts. After adjusting for covariates, race
      remained the strongest predictor of aggressive therapy examined in this study
      [adjusted odds ratio (95% confidence interval) = 11.2 (1.9-64.9)]. CONCLUSIONS:
      In this study, fewer black patients preferred aggressive treatment compared with
      white patients with similar disease severity. These results have important
      clinical implications because use of aggressive treatment improves both short-
      and long-term outcomes in rheumatoid arthritis. Efforts to improve patient
      education and physician communication should be made to ensure that all patients
      have an accurate understanding of the benefits, as well as risks, associated with
      the best available treatment options.

PMID- 19165122
TI  - Caregiver adherence to follow-up after an emergency department visit for common
      pediatric illnesses: Impact on future ED use.
AB  - BACKGROUND: Access to primary care is often a problem for children living in
      urban areas and the rate of emergency department (ED) use can be high. For acute
      childhood illnesses, primary care follow-up is often recommended to prevent
      subsequent ED visits. METHODS: We conducted an observational study of 455
      children with common childhood illnesses, between 6 weeks and 8 years of age,
      presenting to 1 of 3 EDs, and discharged to the community. ED physicians
      recommended that the child visit their primary care physician within 1 to 4 days
      of discharge (ie, "short-term" follow-up). Caregivers were surveyed during the ED
      index visit and after discharge to assess primary care follow-up adherence. We
      collected data on child and caregiver characteristics, type and severity of
      illness at the ED index visit, and ED return visits in the 2-month period after
      the ED index visit. RESULTS: A total of 45.3% of caregivers adhered to short-term
      primary care follow-up. Short-term follow-up adherence was associated with
      greater ED use for the same illness over the subsequent 2 months (odds ratio =
      2.97; 95% confidence interval, 1.31-6.72). Subsequent ED use was greatest for
      children with short-term primary care follow-up and: (1) prior ED use, (2) single
      caregivers, (3) mild severity illnesses at the ED index visit, or (4) younger
      children. ED use after the initial visit did not vary by type of illness or site.
      CONCLUSIONS: There was no evidence that primary care follow-up soon after an ED
      visit was associated with a lower rate of subsequent ED use for common pediatric
      illnesses.

PMID- 19165123
TI  - Objective grading of the anterior eye.
AB  - PURPOSE: To convert objective image analysis of anterior ocular surfaces into
      recognisable clinical grades, in order to provide a more sensitive and reliable
      equivalent to current subjective grading methods; a prospective, randomized study
      correlating clinical grading with digital image assessment. METHODS: The possible
      range of clinical presentations of bulbar and palpebral hyperaemia, palpebral
      roughness and corneal staining were represented by 4 sets of 10 images. The
      images were displayed in random order and graded by 50 clinicians using both
      subjective CCLRU and Efron grading scales. Previously validated objective image
      analysis was performed 3 times on each of the 40 images. Digital measures
      included edge-detection and relative-coloration components. Step-wise regression
      analysis determined correlations between the average subjective grade and the
      objective image analysis measures. RESULTS: Average subjective grades could be
      predicted by a combination of the objective image analysis components. These
      digital "grades" accounted for between 69% (for Efron scale-graded palpebral
      redness) and 98% (for Efron scale-graded bulbar hyperaemia) of the subjective
      variance. CONCLUSIONS: The results indicate that clinicians may use a combination
      of vessel areas and overall hue in their judgment of clinical severity for
      certain conditions. Objective grading can take these aspects into account, and be
      used to predict an average "objective grade" to be used by a clinician in
      describing the anterior eye. These measures are more sensitive and reliable than
      subjective grading while still utilizing familiar terminology, and can be applied
      in research or practice to improve the detection, and monitoring of ocular
      surface changes.

PMID- 19165124
TI  - Evaluation of signs and symptoms in 3- and 9-o'clock staining.
AB  - PURPOSE: This study evaluates the relationship between bulbar hyperemia,
      conjunctival staining, lens comfort and 3- and 9-o'clock corneal staining in
      rigid gas permeable (GP) contact lens wear. METHODS: The study involved 55 GP
      contact lens wearers (with and without 3- and 9-o'clock staining) and 26 non-lens
      wearers. Corneal staining was graded based on a specially designed image grading
      scale developed at the University of Maastricht. The Efron grading scale was used
      to grade bulbar hyperemia and conjunctival staining. Ocular comfort and lens
      comfort were analyzed using a visual analogue scale (VAS) and a questionnaire to
      differentiate symptomatic from asymptomatic subjects. RESULTS: Bulbar hyperemia
      showed a significant but low correlation with corneal staining, and eyes with
      conjunctival staining showed more corneal staining than eyes without conjunctival
      staining. No correlation was found between staining in the nasal and temporal
      regions of the cornea in subjects with substantial 3- and 9-o'clock staining. No
      correlation was found between VAS comfort scores and corneal staining. In those
      subjects with substantial 3- and 9-o'clock staining, symptomatic subjects showed
      more corneal staining than asymptomatic subjects. CONCLUSIONS: Practitioners are
      advised to evaluate both the nasal and temporal regions of the cornea when
      assessing 3- and 9-o'clock staining, and they should be hesitant to rely on the
      amount of bulbar hyperemia for the prediction of the severity of 3- and 9-o'clock
      staining. Assessment of conjunctival staining could potentially be a useful tool
      in clinical practice to identify patients at risk of developing 3- and 9-o'clock
      staining. The lack of correlation between corneal staining and lens comfort
      stresses the need for regular contact lens check-ups in GP lens wearers. It
      appears that the simple registration of the presence or absence of ocular
      symptoms is a better predictor of 3- and 9-o'clock staining than using VAS
      comfort scores.

PMID- 19165125
TI  - Care regimen and lens material influence on silicone hydrogel contact lens
      deposition.
AB  - PURPOSE: To quantitatively detect proteins and cholesterol extracted from worn
      silicone hydrogel contact lenses and determine the effect of various lens care
      solutions on deposit accumulation. METHODS: Contact lenses, made from different
      polymers and worn on a daily wear schedule with different lens care solutions,
      were collected. Lipid and protein deposits were extracted by methanol:chloroform
      (1:1, v/v) and protein extraction solution (containing urea and surfactant),
      respectively. Lipid extracts were separated and cholesterol quantified using thin
      layer chromatography. Protein extracts were quantified using standard techniques.
      RESULTS: Among all lenses tested, Balafilcon A lenses exhibited greatest
      extracted cholesterol (4.1 to 8.2 microg/lens) and total protein (5.4 to 23.2
      microg/lens). AQuify was the most effective solution in reducing extracted
      deposits, especially extracted protein, from Balafilcon A lenses. AQuify and Opti
      Free RepleniSH solutions were most effective in reducing extracted cholesterol
      from Senofilcon A and Galyfilcon A lenses, respectively. Use of Opti-Free Express
      solution resulted in more extracted protein from Lotrafilcon B lenses than use of
      other solutions. Generally, Lotrafilcon B, Senofilcon A, and Galyfilcon A lenses
      accumulated relatively low amount of proteins. Lotrafilcon B lenses accumulated
      the least amount of cholesterol deposit among all lenses tested regardless of
      solution used. CONCLUSIONS: Lens polymer (possibly associated with surface
      characteristics) is a prominent factor affecting lipid and protein accumulation.
      Within a lens polymer type, lens care solutions exhibit varying effectiveness in
      reducing protein and lipid accumulation.

PMID- 19165126
TI  - Evaluation of infant accommodation using retinoscopy and photoretinoscopy.
AB  - PURPOSE: To compare PlusOptix PowerRefractor (PR) and Monocular Estimation Method
      (MEM) for measurement of infant accommodation and to assess the usefulness of
      applying individual calibration factors to PR data. METHODS: Subjects were 41
      infants aged 3 to 12 months. Accommodative response was measured by MEM and PR at
      33 and 57 cm, acuity by Teller Acuity Cards, and cycloplegic refractive error
      (RE) (tropicamide 1%) by retinoscopy (Wet Ret) and PR (PR C). Monocular wear of a
      +2.00 diopter (D) and +4.00 D lens established a PR calibration factor for each
      subject. RESULTS: The median individual calibration slope was significantly
      different from 1.0 (+0.91; Wilcoxon signed-rank test: p = 0.03), yet there was no
      correlation between individual calibration slopes and the difference in RE by Wet
      Ret and PR C (rs = 0.05, p = 0.76). For 19 infants with an accommodative response
      slope by PR of >0.50, the mean lag was not significantly different between
      methods (0.50 D PR, 0.48 D MEM; p = 0.92; 95% LoA = +/-1.78 D). Despite the
      improvement in acuity with age (rp = -0.56, p < 0.0001), neither age nor acuity
      had a significant effect on accommodative error. Lag was greater at 57 cm (0.69
      D) than 33 cm (0.30 D, F1, 18 = 6.3, p = 0.022), but lag was unrelated to RE (F1,
      17 = 3.3, p = 0.09). Accommodative response slopes for boys were larger (1.5)
      than for girls (1.0; F1, 17 = 9.5, p = 0.007). CONCLUSION: MEM and PR provided
      similar estimates of RE and of accommodative lag once the PR data were screened
      for inattention using an accommodative response slope criterion. Adult-like
      accommodative responses between 3 and 12 months of age suggest that acuity at
      these ages is not limited by accommodative immaturity. Further, mature
      accommodation may attenuate RE-related defocus signals for emmetropization.

PMID- 19165127
TI  - Compartment syndrome in a child secondary to acute osteomyelitis of the ulna.

PMID- 19165128
TI  - Mollicute infections in neonates.
AB  - Mollicutes can cause a wide spectrum of disease, especially in neonates. To
      better define their disease spectrum in the United States, we reviewed the
      results of >14,000 mollicute isolates, including 1346 from neonates. When
      mollicute infection is suspected, clinicians should alert laboratories, which
      will optimize methods of detection.

PMID- 19165129
TI  - Chronic granulomatous disease in an adolescent with recurrent impetigo and
      cholecystectomy.
AB  - Chronic granulomatous disease is a rare primary immunodeficiency disorder
      resulting from a defect in the microbicidal activity of phagocytes. Patients are
      susceptible to certain bacterial and fungal infections, as well as other
      inflammatory complications. We report the case of a 12-year-old girl with
      recurrent impetigo whose history of cholecystitis triggered an evaluation that
      revealed chronic granulomatous disease.

PMID- 19165130
TI  - Efficacy of non-nucleoside reverse transcriptase inhibitor-based highly active
      antiretroviral therapy in Thai HIV-infected children aged two years or less.
AB  - Twenty-six Thai HIV-infected children, aged 2 years or less were prospectively
      enrolled to receive non-nucleoside reverse transcription inhibitor-based highly
      active antiretroviral therapy (HAART). Twenty-two children (85%) had World Health
      Organization clinical stage 3 or 4. The median baseline CD4 cell percentage and
      plasma HIV RNA were 17% and 5.9 log 10 copies/mL, respectively. The median age at
      HAART initiation was 9.8 months (range, 1.5-24.0). One child died. The mean CD4
      cell percentages at 24, 48, and 96 weeks of treatment were 26%, 31%, and 37%,
      respectively. The proportions of children with virologic suppression (<400
      copies/mL) at week 24 and 48 were 14/26 (54%) and 19/26 (73%), respectively. Non
      nucleoside reverse transcription inhibitor-based HAART is safe and effective in
      HIV-infected young children in a resource-limited setting.

PMID- 19165131
TI  - Papular-purpuric gloves and socks syndrome in children and adolescents.
AB  - We describe the case of a 12-year-old boy with gloves and socks syndrome caused
      by coinfection with HHV-6 and PVB19, and review the published cases from 5 to 18
      years of age to profile the disease in this age group. The review of the
      literature yielded 25 cases of gloves and socks syndrome. Most patients were
      febrile and had acute PVB19 infection.

PMID- 19165132
TI  - Discordance between Staphylococcus aureus nasal colonization and skin infections
      in children.
AB  - We examined nasal carriage of Staphylococcus aureus in otherwise healthy children
      presenting with skin and soft tissue infections. We found high rates of nasal
      colonization with S. aureus, but significant discordance between nasal and wound
      isolates. Recurrent skin and soft tissue infections were common but unrelated to
      baseline methicillin-resistant S. aureus nasal colonization status.

PMID- 19165133
TI  - Pertussis vaccine: a critique.
AB  - A critical level of serum IgG pertussis toxin antibody is both essential and
      sufficient to confer individual and herd immunity to pertussis. Monocomponent
      pertussis toxoid conferred such immunity in Sweden and in Denmark. We refute the
      notion that filamentous hemagglutinin, pertactin, and fimbriae add to the
      immunity conferred by pertussis toxoid and describe the artifact created when
      efficacy is estimated for multicomponent pertussis vaccines. Lastly, the
      genetically-inactivated mutant pertussis toxoid is safer, more immunogenic, and
      should be more effective than the current chemically-inactivated pertussis toxin.

PMID- 19165134
TI  - Vaccine preventable infections and multiple organ dysfunction syndrome in
      critically ill children in China.
AB  - BACKGROUND: Multiple organ dysfunction syndrome (MODS) is a major cause of
      mortality in PICUs in industrialized countries. As developing countries become
      more advanced, PICU care comes into reach. The aim of this study was to examine
      MODS in a PICU in China in comparison with other countries. METHODS: A
      retrospective 5-year audit (2001-2006) of MODS cases in a 6-bed PICU in the
      Second Hospital of Lanzhou University, China. RESULTS: Of the 332 PICU patients,
      176 (53%) had MODS; the mean age was 35 months, and 60% were <1 year of age.
      Infectious diseases were the predominant factor underlying MODS (128/176; 73%)
      with 24% attributable to potentially vaccine preventable infections (14 to
      Haemophilus influenzae b, 13 to Streptococcus pneumoniae, and 4 to Neisseria
      meningitidis). The case fatality rate for MODS was 49% with no difference between
      infectious or noninfectious causes (48% vs. 52%; P > 0.05). The frequency of
      organ dysfunction in MODS was in decreasing order: respiratory (95%),
      cardiovascular (89%), gastrointestinal (39%), neurologic (35%), hematologic
      (16%), renal (14%), and hepatic (4%) systems. Mortality rose with increasing
      number of organs involved. Gastrointestinal system failure was more common in
      MODS caused by infection than noninfection (45% vs. 23%; P <0.01) and had a
      higher mortality (72% vs. 34%; P < 0.001). The case fatality rate for MODS in
      this study was comparable to rates in other developing countries but higher than
      in industrialized countries. CONCLUSIONS: MODS is a major cause of mortality in
      PICU patients in China. In China, infection-related MODS PICU cases could
      potentially be reduced to rates closer to those in industrialized countries, if
      conjugated H. influenzae b and conjugated pneumococcal vaccines were introduced
      into routine practice.

PMID- 19165135
TI  - Risk of adverse birth outcome after group B meningococcal disease: results from a
      Danish national cohort.
AB  - BACKGROUND: Group B meningococcal (GBM) disease induces antibodies that react in
      vitro with neural cell adhesion molecules in fetal brain tissue. Because IgG
      antibodies to GBM cross the placenta, the authors investigated whether women with
      a previous GBM disease had an increased risk of giving birth to preterm or to
      stillborn infants and whether the live-born children had an increased risk of
      birth defects. METHODS: Data were obtained from 4 national registries in the
      period 1974-2005 to form 2 cohorts: (1) 1422 women with confirmed GBM disease,
      and (2) their 502 firstborn children. RESULTS: Overall, there was no increased
      risk of preterm or stillbirths among the first cohort. Among the children, there
      was no increased risk of being born small for the gestational age, having birth
      defects (OR: 1.00; 95% CI: 0.53-1.90), diseases of the nervous system (HR: 0.38;
      95% CI: 0.08-1.74), or any diseases within the first 3 years of life (HR: 1.06;
      95% CI: 0.78-1.45) compared to births from a reference population with prior
      group C meningococcal disease. CONCLUSIONS: The results do not support the
      proposal that GBM is associated with immunoreactive disease that may affect the
      health of the offspring and are consistent with previous findings that GBM
      disease is not associated with an increased risk of autoimmune disease.

PMID- 19165136
TI  - Multistate outbreaks of Salmonella infections associated with live poultry-
      United States, 2007.
AB  - During June 2007, the Minnesota Department of Health (MDH) Public Health
      Laboratory examined specimens from two ill persons and identified Salmonella
      Montevideo isolates with the same pulsed-field gel electrophoresis pattern (PFGE
      pattern 1). MDH officials interviewed the patients and determined that both had
      been exposed to chickens originating from the same Iowa hatchery (hatchery A). In
      September 2007, a cluster of seven additional infections with PFGE pattern 1 was
      identified in North Dakota; all seven patients had been exposed to baby chicks
      obtained from hatchery A. A subsequent nationwide investigation identified a
      total of 65 S. Montevideo isolates with PFGE pattern 1 during 2007 and a likely
      association with exposure to live poultry purchased at feed stores or by mail
      order from hatchery A or seven other hatcheries in four states. Meanwhile,
      throughout 2007, a separate outbreak was occurring that involved infections with
      a different S. Montevideo strain (PFGE pattern 2). A total of 64 of those
      isolates were identified in 23 states during 2007. Exposure to live poultry from
      a hatchery in New Mexico (hatchery B) and a hatchery in Ohio (hatchery C) was
      associated with those infections. This report describes two distinct and
      unrelated outbreaks, which demonstrate the ongoing risk for Salmonella infection
      from live poultry purchased from agricultural feed stores or directly from mail
      order hatcheries. The mail order hatchery industry is a source of bird-associated
      human pathogens, such as Salmonella, and comprehensive infection-control
      strategies are needed to prevent additional illnesses resulting from live poultry
      contact.

PMID- 19165137
TI  - State-specific smoking-attributable mortality and years of potential life lost-
      United States, 2000-2004.
AB  - Smoking can cause lung and other cancers, coronary heart disease, stroke, chronic
      respiratory disease, and other diseases. In 2008, CDC reported that cigarette
      smoking and exposure to secondhand smoke resulted in an estimated 443,000 deaths
      and 5.1 million years of potential life lost (YPLL) annually in the United States
      during 2000-2004. This report presents state-specific average annual smoking
      attributable mortality (SAM) and YPLL estimates for the same period among adults
      aged >/=35 years. The report also compares 2000-2004 average annual SAM rates per
      100,000 population with rates for 1996-1999. The analysis was based on data from
      CDC's Smoking-Attributable Mortality, Morbidity, and Economic Costs (SAMMEC)
      system. Substantial variation in average annual number of deaths attributed to
      smoking during 2000-2004 occurred among the states (range: 492 [Alaska] to 36,687
      [California]). From 1996-1999 to 2000-2004, declines in SAM rates occurred in 49
      states and the District of Columbia (DC), reflecting progress made in lowering
      smoking prevalence in the United States during the past 40 years. Rates declined
      in men in 49 states and DC, but declined in women in only 32 states. To reduce
      SAM rates further, comprehensive evidence-based approaches for preventing smoking
      initiation and increasing cessation need to be implemented fully, and states
      should fund tobacco control activities at the level recommended by CDC.

PMID- 19165138
TI  - Guidelines for field triage of injured patients. Recommendations of the National
      Expert Panel on Field Triage.
AB  - In the United States, injury is the leading cause of death for persons aged 1--44
      years, and the approximately 800,000 emergency medical services (EMS) providers
      have a substantial impact on the care of injured persons and on public health. At
      an injury scene, EMS providers determine the severity of injury, initiate medical
      management, and identify the most appropriate facility to which to transport the
      patient through a process called "field triage." Although basic emergency
      services generally are consistent across hospital emergency departments (EDs),
      certain hospitals have additional expertise, resources, and equipment for
      treating severely injured patients. Such facilities, called "trauma centers," are
      classified from Level I (centers providing the highest level of trauma care) to
      Level IV (centers providing initial trauma care and transfer to a higher level of
      trauma care if necessary) depending on the scope of resources and services
      available. The risk for death of a severely injured person is 25% lower if the
      patient receives care at a Level I trauma center. However, not all patients
      require the services of a Level I trauma center; patients who are injured less
      severely might be served better by being transported to a closer ED capable of
      managing milder injuries. Transferring all injured patients to Level I trauma
      centers might overburden the centers, have a negative impact on patient outcomes,
      and decrease cost effectiveness. In 1986, the American College of Surgeons
      developed the Field Triage Decision Scheme (Decision Scheme), which serves as the
      basis for triage protocols for state and local EMS systems across the United
      States. The Decision Scheme is an algorithm that guides EMS providers through
      four decision steps (physiologic, anatomic, mechanism of injury, and special
      considerations) to determine the most appropriate destination facility within the
      local trauma care system. Since its initial publication in 1986, the Decision
      Scheme has been revised four times. In 2005, with support from the National
      Highway Traffic Safety Administration, CDC began facilitating revision of the
      Decision Scheme by hosting a series of meetings of the National Expert Panel on
      Field Triage, which includes injury-care providers, public health professionals,
      automotive industry representatives, and officials from federal agencies. The
      Panel reviewed relevant literature, presented its findings, and reached consensus
      on necessary revisions. The revised Decision Scheme was published in 2006. This
      report describes the process and rationale used by the Expert Panel to revise the
      Decision Scheme.

PMID- 19165139
TI  - Retroviral integrase superfamily: the structural perspective.
AB  - The retroviral integrase superfamily (RISF) comprises numerous important nucleic
      acid-processing enzymes, including transposases, integrases and various
      nucleases. These enzymes are involved in a wide range of processes such as
      transposition, replication and repair of DNA, homologous recombination, and RNA
      mediated gene silencing. Two out of the four enzymes that are encoded by the
      human immunodeficiency virus--RNase H1 and integrase--are members of this
      superfamily. RISF enzymes act on various substrates, and yet show remarkable
      mechanistic and structural similarities. All share a common fold of the catalytic
      core and the active site, which is composed primarily of carboxylate residues.
      Here, I present RISF proteins from a structural perspective, describing the
      individual members and the common and divergent elements of their structures, as
      well as the mechanistic insights gained from the structures of RNase H1 enzyme
      complexes with RNA/DNA hybrids.

PMID- 19165140
TI  - Genomics in school. Science & society series on convergence research.

PMID- 19165141
TI  - The rock 'n' roll of knowledge co-production. Science & Society Series on
      Convergence Research.

PMID- 19165142
TI  - Membrane trafficking heats up in Pavia. Golgi Meeting on Membrane Trafficking in
      Global Cellular Responses.

PMID- 19165143
TI  - Crystal structure of CbpF, a bifunctional choline-binding protein and autolysis
      regulator from Streptococcus pneumoniae.
AB  - Phosphorylcholine, a crucial component of the pneumococcal cell wall, is
      essential in bacterial physiology and in human pathogenesis because it binds to
      serum components of the immune system and acts as a docking station for the
      family of surface choline-binding proteins. The three-dimensional structure of
      choline-binding protein F (CbpF), one of the most abundant proteins in the
      pneumococcal cell wall, has been solved in complex with choline. CbpF shows a new
      modular structure composed both of consensus and non-consensus choline-binding
      repeats, distributed along its length, which markedly alter its shape, charge
      distribution and binding ability, and organizing the protein into two well
      defined modules. The carboxy-terminal module is involved in cell wall binding and
      the amino-terminal module is crucial for inhibition of the autolytic LytC
      muramidase, providing a regulatory function for pneumococcal autolysis.

PMID- 19165144
TI  - RNA pol II subunit RPB7 is required for RNA pol I-mediated transcription in
      Trypanosoma brucei.
AB  - In the protozoan parasite Trypanosoma brucei, the two main surface glycoprotein
      genes are transcribed by RNA polymerase I (pol I) instead of RNA pol II, the
      polymerase committed to the production of mRNA in eukaryotes. This unusual
      feature might be accomplished by the recruitment of specific subunits or
      cofactors that allow pol I to transcribe protein-coding RNAs. Here, we report
      that transcription mediated by pol I requires TbRPB7, a dissociable subunit of
      the pol II complex. TbRPB7 was found to interact with two pol I-specific
      subunits, TbRPA1 and TbRPB6z. Pol I-specific transcription was affected on
      depletion of TbRPB7 in run-on assays, whereas recombinant TbRPB7 increased
      transcription driven by a pol I promoter. These results represent a unique
      example of a functional RNA polymerase chimaera consisting of a core pol I
      complex that recruits a specific pol II subunit.

PMID- 19165145
TI  - BLM helicase measures DNA unwound before switching strands and hRPA promotes
      unwinding reinitiation.
AB  - Bloom syndrome (BS) is a rare genetic disorder characterized by genomic
      instability and a high predisposition to cancer. The gene defective in BS, BLM,
      encodes a member of the RecQ family of 3'-5' DNA helicases, and is proposed to
      function in recombinational repair during DNA replication. Here, we have utilized
      single-molecule fluorescence resonance energy transfer microscopy to examine the
      behaviour of BLM on forked DNA substrates. Strikingly, BLM unwound individual DNA
      molecules in a repetitive manner, unwinding a short length of duplex DNA followed
      by rapid reannealing and reinitiation of unwinding in several successions. Our
      results show that a monomeric BLM can 'measure' how many base pairs it has
      unwound, and once it has unwound a critical length, it reverses the unwinding
      reaction through strand switching and translocating on the opposing strand.
      Repetitive unwinding persisted even in the presence of hRPA, and interaction
      between wild-type BLM and hRPA was necessary for unwinding reinitiation on hRPA
      coated DNA. The reported activities may facilitate BLM processing of stalled
      replication forks and illegitimately formed recombination intermediates.

PMID- 19165146
TI  - Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export
      of HSP70 mRNA.
AB  - In metazoans, nuclear export of bulk mRNA is mediated by Tap-p15, a conserved
      heterodimeric export receptor that cooperates with adaptor RNA-binding proteins.
      In this article, we show that Thoc5, a subunit of the mammalian TREX complex,
      binds to a distinct surface on the middle (Ntf2-like) domain of Tap. Notably,
      adaptor protein Aly and Thoc5 can simultaneously bind to non-overlapping binding
      sites on Tap-p15. In vivo, Thoc5 was not required for bulk mRNA export. However,
      nuclear export of HSP70 mRNA depends on both Thoc5 and Aly. Consistent with a
      function as a specific export adaptor, Thoc5 exhibits in vitro RNA-binding
      activity and is associated with HSP70 mRNPs in vivo as a component of the stable
      THO complex. Thus, through the combinatorial use of an adaptor (e.g., Aly) and co
      adapter (e.g., Thoc5), Tap-p15 could function as an export receptor for different
      classes of mRNAs.

PMID- 19165147
TI  - dMec: a novel Mi-2 chromatin remodelling complex involved in transcriptional
      repression.
AB  - The ATP-dependent chromatin remodeller Mi-2 functions as a transcriptional
      repressor and contributes to the suppression of cell fates during development in
      several model organisms. Mi-2 is the ATPase subunit of the conserved Nucleosome
      Remodeling and Deacetylation (NuRD) complex, and transcriptional repression by Mi
      2 is thought to be dependent on its associated histone deacetylase. Here, we have
      purified a novel dMi-2 complex from Drosophila that is distinct from dNuRD. dMec
      (dMEP-1 complex) is composed of dMi-2 and dMEP-1. dMec is a nucleosome-stimulated
      ATPase that is expressed in embryos, larval tissues and adult flies.
      Surprisingly, dMec is far more abundant than dNuRD and constitutes the major dMi
      2-containing complex. Both dNuRD and dMec associate with proneural genes of the
      achaete-scute complex. However, despite lacking a histone deacetylase subunit,
      only dMec contributes to the repression of proneural genes. These results reveal
      an unexpected complexity in the composition and function of Mi-2 complexes.

PMID- 19165148
TI  - Interaction of COP1 and UVR8 regulates UV-B-induced photomorphogenesis and stress
      acclimation in Arabidopsis.
AB  - The ultraviolet-B (UV-B) portion of the solar radiation functions as an
      environmental signal for which plants have evolved specific and sensitive UV-B
      perception systems. The UV-B-specific UV RESPONSE LOCUS 8 (UVR8) and the
      multifunctional E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) are
      key regulators of the UV-B response. We show here that uvr8-null mutants are
      deficient in UV-B-induced photomorphogenesis and hypersensitive to UV-B stress,
      whereas overexpression of UVR8 results in enhanced UV-B photomorphogenesis,
      acclimation and tolerance to UV-B stress. By using sun simulators, we provide
      evidence at the physiological level that UV-B acclimation mediated by the UV-B
      specific photoregulatory pathway is indeed required for survival in sunlight. At
      the molecular level, we demonstrate that the wild type but not the mutant UVR8
      and COP1 proteins directly interact in a UV-B-dependent, rapid manner in planta.
      These data collectively suggest that UV-B-specific interaction of COP1 and UVR8
      in the nucleus is a very early step in signalling and responsible for the plant's
      coordinated response to UV-B ensuring UV-B acclimation and protection in the
      natural environment.

PMID- 19165149
TI  - Gene dosage compensation calibrates four regulatory RNAs to control Vibrio
      cholerae quorum sensing.
AB  - Quorum sensing is a mechanism of cell-to-cell communication that allows bacteria
      to coordinately regulate gene expression in response to changes in cell
      population density. At the core of the Vibrio cholerae quorum-sensing signal
      transduction pathway reside four homologous small RNAs (sRNAs), named the quorum
      regulatory RNAs 1-4 (Qrr1-4). The four Qrr sRNAs are functionally redundant. That
      is, expression of any one of them is sufficient for wild-type quorum-sensing
      behaviour. Here, we show that the combined action of two feedback loops, one
      involving the sRNA-activator LuxO and one involving the sRNA-target HapR,
      promotes gene dosage compensation between the four qrr genes. Gene dosage
      compensation adjusts the total Qrr1-4 sRNA pool and provides the molecular
      mechanism underlying sRNA redundancy. The dosage compensation mechanism is
      exquisitely sensitive to small perturbations in Qrr levels. Precisely maintained
      Qrr levels are required to direct the proper timing and correct patterns of
      expression of quorum-sensing-regulated target genes.

PMID- 19165150
TI  - dsRNA with 5' overhangs contributes to endogenous and antiviral RNA silencing
      pathways in plants.
AB  - In plants, SGS3 and RNA-dependent RNA polymerase 6 (RDR6) are required to convert
      single- to double-stranded RNA (dsRNA) in the innate RNAi-based antiviral
      response and to produce both exogenous and endogenous short-interfering RNAs.
      Although a role for RDR6-catalysed RNA-dependent RNA polymerisation in these
      processes seems clear, the function of SGS3 is unknown. Here, we show that SGS3
      is a dsRNA-binding protein with unexpected substrate selectivity favouring 5'
      overhang-containing dsRNA. The conserved XS and coiled-coil domains are
      responsible for RNA-binding activity. Furthermore, we find that the V2 protein
      from tomato yellow leaf curl virus, which suppresses the RNAi-based host immune
      response, is a dsRNA-binding protein with similar specificity to SGS3. In
      competition-binding experiments, V2 outcompetes SGS3 for substrate dsRNA
      recognition, whereas a V2 point mutant lacking the suppressor function in vivo
      cannot efficiently overcome SGS3 binding. These findings suggest that SGS3
      recognition of dsRNA containing a 5' overhang is required for subsequent steps in
      RNA-mediated gene silencing in plants, and that V2 functions as a viral
      suppressor by preventing SGS3 from accessing substrate RNAs.

PMID- 19165152
TI  - Spatially and kinetically resolved changes in the conformational dynamics of the
      Hsp90 chaperone machine.
AB  - The highly conserved 90 kDa heat shock protein (Hsp90) chaperones use ATP to
      regulate the stability and activity of many signalling molecules like protein
      kinases and transcription factors. Studies using crystallography, electron
      microscopy and small-angle X-ray scattering yielded controversial results for the
      conformational states that these dimeric multidomain proteins assume while
      progressing through the ATPase cycle. To better understand the molecular
      mechanism of Hsp90 proteins, we studied the conformational dynamics of the
      Escherichia coli homologue HtpG in solution using amide hydrogen exchange mass
      spectrometry (HX-MS) and fluorescence spectroscopy. A conformation-sensitive
      fluorescent probe allowed to elucidate the ATPase cycle of HtpG. Continuous
      labelling and pulse-labelling HX-MS experiments revealed major ATP-induced
      conformational changes throughout the protein that do not occur simultaneously,
      but progress surprisingly slow from the immediate nucleotide-binding site towards
      the N terminus and the middle domain. The conversion between the different
      conformational states is rate limiting for ATP hydrolysis, and the nucleotide
      coordinating residue, Glu34, is important for the rate constant of conversion.
      Our findings, for the first time, allow to kinetically resolve changes in the
      conformational dynamics of individual structural elements of Hsp90.

PMID- 19165151
TI  - Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death.
AB  - Dying tumour cells can elicit a potent anticancer immune response by exposing the
      calreticulin (CRT)/ERp57 complex on the cell surface before the cells manifest
      any signs of apoptosis. Here, we enumerate elements of the pathway that mediates
      pre-apoptotic CRT/ERp57 exposure in response to several immunogenic anticancer
      agents. Early activation of the endoplasmic reticulum (ER)-sessile kinase PERK
      leads to phosphorylation of the translation initiation factor eIF2alpha, followed
      by partial activation of caspase-8 (but not caspase-3), caspase-8-mediated
      cleavage of the ER protein BAP31 and conformational activation of Bax and Bak.
      Finally, a pool of CRT that has transited the Golgi apparatus is secreted by
      SNARE-dependent exocytosis. Knock-in mutation of eIF2alpha (to make it non
      phosphorylatable) or BAP31 (to render it uncleavable), depletion of PERK, caspase
      8, BAP31, Bax, Bak or SNAREs abolished CRT/ERp57 exposure induced by
      anthracyclines, oxaliplatin and ultraviolet C light. Depletion of PERK, caspase-8
      or SNAREs had no effect on cell death induced by anthracyclines, yet abolished
      the immunogenicity of cell death, which could be restored by absorbing
      recombinant CRT to the cell surface.

PMID- 19165153
TI  - Matrix alkalinization: a novel mitochondrial signal for sustained pancreatic beta
      cell activation.
AB  - Nutrient secretagogues activate mitochondria of the pancreatic beta-cell through
      the provision of substrate, hyperpolarisation of the inner mitochondrial membrane
      and mitochondrial calcium rises. We report that mitochondrial matrix pH, a
      parameter not previously studied in the beta-cell, also exerts an important
      control function in mitochondrial metabolism. During nutrient stimulation matrix
      pH alkalinises, monitored by the mitochondrial targeted fluorescent pH-sensitive
      protein mtAlpHi or (31)P-NMR inorganic phosphate chemical shifts following
      saturation transfer. Compared with other cell types, the resting mitochondrial pH
      was surprisingly low, rising from pH 7.25 to 7.7 during nutrient stimulation of
      rat beta-cells. As cytosolic alkalinisation to the nutrient was of much smaller
      amplitude, the matrix alkalinisation was accompanied by a pronounced increase of
      the DeltapH across the inner mitochondrial membrane. Furthermore, matrix
      alkalinisation closely correlates with the cytosolic ATP net increase, which is
      also associated with elevated ATP synthesis rates in mitochondria. Preventing
      DeltapH increases in permeabilised cells abrogated substrate-driven ATP
      synthesis. We propose that the mitochondrial pH and DeltapH are key determinants
      of mitochondrial energy metabolism and metabolite transport important for cell
      activation.

PMID- 19165154
TI  - Adipogenic cascade can be induced without adipogenic media by a human adenovirus.
AB  - Several metabolic abnormalities are associated with relative excess or deficiency
      of adipose tissue. Identifying the regulators of adipogenic differentiation is
      critical for its successful manipulation. Ad36, a human adenovirus, is a novel
      factor that promotes adipogenesis. We exploited the adipogenic potential of Ad36
      to reveal exogenous modifiers of adipogenesis in rodent preadipocyte cell line in
      the presence or absence of differentiation inducers methyl-isobutyl-xanthine,
      dexamethasone, and insulin (M, D, and I; MDI). A nonadipogenic human adenovirus
      Ad2 was used as a negative control for viral infection. First, we confirmed that,
      Ad36, but not Ad2, increases lipid accumulation in the presence or absence of
      MDI. Time-course studies for expression of key genes of adipogenic cascade showed
      that it is Ad36, but not Ad2, which downregulated preadipocyte marker gene
      Wnt10b, and upregulated expression of early (C/EBPDelta and C/EBPbeta),
      intermediate (PPARgamma2), and late genes (aP2 and G3PDH) of adipogenic cascade
      even in the absence of MDI. In the presence of MDI, onset of expression of
      adipogenic genes coincided for Ad36 and control groups, but the expressions were
      significantly greater for the Ad36 group. Next, we observed that attenuation of
      Ad36 mRNA expression by an antiadenoviral agent reduced 3T3-L1 differentiation,
      indicating that viral mRNA expression is required for the process. Furthermore,
      with or without MDI or its components, Ad36 significantly increased lipid
      accumulation in 3T3-L1 cells. Cell confluency at the time of Ad36 infection
      positively influenced lipid accumulation. The results reveal that Ad36 is an MDI
      independent exogenous regulator of the adipogenic process. Elucidating the
      molecular pathways involved may reveal novel regulatory controls of adipogenesis.

PMID- 19165155
TI  - Genome-wide linkage and association analyses to identify genes influencing
      adiponectin levels: the GEMS Study.
AB  - Adiponectin has a variety of metabolic effects on obesity, insulin sensitivity,
      and atherosclerosis. To identify genes influencing variation in plasma
      adiponectin levels, we performed genome-wide linkage and association scans of
      adiponectin in two cohorts of subjects recruited in the Genetic Epidemiology of
      Metabolic Syndrome Study. The genome-wide linkage scan was conducted in families
      of Turkish and southern European (TSE, n = 789) and Northern and Western European
      (NWE, N = 2,280) origin. A whole genome association (WGA) analysis (500K
      Affymetrix platform) was carried out in a set of unrelated NWE subjects
      consisting of approximately 1,000 subjects with dyslipidemia and 1,000 overweight
      subjects with normal lipids. Peak evidence for linkage occurred at chromosome
      8p23 in NWE subjects (lod = 3.10) and at chromosome 3q28 near ADIPOQ, the
      adiponectin structural gene, in TSE subjects (lod = 1.70). In the WGA analysis,
      the single-nucleotide polymorphisms (SNPs) most strongly associated with
      adiponectin were rs3774261 and rs6773957 (P < 10(-7)). These two SNPs were in
      high linkage disequilibrium (r(2) = 0.98) and located within ADIPOQ.
      Interestingly, our fourth strongest region of association (P < 2 x 10(-5)) was to
      an SNP within CDH13, whose protein product is a newly identified receptor for
      high-molecular-weight species of adiponectin. Through WGA analysis, we confirmed
      previous studies showing SNPs within ADIPOQ to be strongly associated with
      variation in adiponectin levels and further observed these to have the strongest
      effects on adiponectin levels throughout the genome. We additionally identified a
      second gene (CDH13) possibly influencing variation in adiponectin levels. The
      impact of these SNPs on health and disease has yet to be determined.

PMID- 19165156
TI  - Altering PPARgamma ligand selectivity impairs adipogenesis by thiazolidinediones
      but not hormonal inducers.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) acts as a ligand
      dependent transcription factor with a key role in mediating adipocyte
      differentiation and insulin sensitivity. Recently, we and others have shown that
      PPARgamma recruits the nuclear corepressors NCoR and silencing mediator for
      retinoid and thyroid hormone receptors (SMRT) to modulate adipogenesis. While the
      synthetic ligands for PPARgamma, the thiazolidinediones (TZD), are widely used in
      the treatment of type 2 diabetes mellitus, the biologically relevant endogenous
      PPARgamma ligand involved in adipogenesis remains unidentified. To further
      understand the role of ligand binding and corepressor interaction in PPARgamma
      mediated adipogenesis, a mutation was introduced in the ligand-binding domain
      (LBD) of murine PPARgamma. PPARgammamut was created via two amino acid
      substitutions known to be major determinants of ligand selectivity among PPAR
      isotypes, H323Y and R288M. These mutations alter PPARgamma to the corresponding
      residues of the PPARalpha. Characterizing the in vitro functional properties of
      this mutant, we show that PPARgammamut preferentially responds to the PPARalpha
      agonist, WY-14643, over the TZD, pioglitazone. When expressed in 3T3-L1
      preadipocytes using recombinant adenovirus, wild-type PPARgamma leads to
      adipocyte formation with both hormonal and TZD treatment. PPARgammamut blocks the
      upregulation of adipocyte-specific proteins by TZD, but surprisingly, not by
      standard hormonal inducers. Our data suggest that TZDs and the purported
      endogenous ligand do not interact in the same way with the PPARgamma LBD. We
      propose that the endogenous ligand has distinct properties that allow for
      promiscuity within the hydrophobic PPAR ligand-binding pocket, yet fosters
      appropriate cofactor recruitment and release to allow adipogenesis to proceed.

PMID- 19165158
TI  - Psychosocial functioning improves following adolescent bariatric surgery.
AB  - The aims of the present study were to examine changes in health-related quality
      of life (HRQOL) and depressive symptoms in adolescents with extreme obesity
      undergoing Roux-en-Y gastric bypass (RYGBP) across the first postoperative year.
      A prospective longitudinal observational study of 31 adolescent patients
      undergoing RYGBP at a pediatric medical center (mean = 16.4 years; 64.5% females,
      mean BMI 63.5; 97% of study eligible and consecutive patients) was conducted.
      Participants completed two adolescent HRQOL measures, the PedsQL (generic) and
      the IWQOL-Kids (weight-related), the Beck Depression Inventory (BDI), and height
      and weight were measured at three time points: baseline, and 6 and 12 months
      following RYGBP. Prior to RYGBP, significant impairments in HRQOL were documented
      and 38.7% reported depressive symptomatology in the clinical range. As expected,
      BMI and depressive symptoms decreased and HRQOL improved from baseline to 12
      months post-RYGBP. Linear mixed modeling analyses detected several nonlinear
      slopes in BMI, depressive symptoms, and the majority of HRQOL domains over time
      with deceleration in these postoperative changes beginning at the 6th month time
      point. In contrast, the rate of change in weight-related social relations was
      linear (e.g., no deceleration), indicating continued improvement across the first
      postoperative year. Adolescent RYGBP results in significant improvement in HRQOL
      and depressive symptomatology over the first postoperative year. Longer-term
      follow-up will be critical to determine adolescent weight and psychosocial
      trajectories, their interrelations, and what role psychosocial status plays in
      continued weight loss, maintenance, and regain.

PMID- 19165157
TI  - Inflammation and race and gender differences in computerized tomography-measured
      adipose depots.
AB  - A growing body of evidence has consistently shown a correlation between obesity
      and chronic subclinical inflammation. It is unclear whether the size of specific
      adipose depots is more closely associated with concentrations of inflammatory
      markers than overall adiposity. This study investigated the relationship between
      inflammatory markers and computerized tomography-derived abdominal visceral and
      subcutaneous fat and thigh intermuscular and subcutaneous fat in older white and
      black adults. Data were from 2,651 black and white men and women aged 70-79 years
      participating in the Health, Aging, and Body Composition (Health ABC) study.
      Inflammatory markers, interleukin-6 (IL-6), C-reactive protein (CRP), and tumor
      necrosis factor-alpha (TNF-alpha) were obtained from serum samples. Abdominal
      visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat were
      quantified on computerized tomography images. Linear regression analysis was used
      to evaluate the cross-sectional relationship between specific adipose depots and
      inflammatory markers in four race/gender groups. As expected, blacks have less
      visceral fat than whites and women less visceral fat than men. However, abdominal
      visceral adiposity was most consistently associated with significantly higher IL
      6 and CRP concentrations in all race/gender groups (P < 0.05), even after
      controlling for general adiposity. Thigh intermuscular fat had an inconsistent
      but significant association with inflammation, and there was a trend toward lower
      inflammatory marker concentration with increasing thigh subcutaneous fat in white
      and black women. Despite the previously established differences in abdominal fat
      distribution across gender and race, visceral fat remained a significant
      predictor of inflammatory marker concentration across all four subgroups
      examined.

PMID- 19165159
TI  - Genetic and environmental contributions to BMI in adolescent and young adult
      women.
AB  - The objective of this study was to determine the genetic and environmental
      contributions to variation in BMI over time in European-American (EA) and African
      American (AA) adolescent and young adult women. Self-reported BMI (kg/m(2)) data
      from 2,816 EA (1,306 twin pairs, 56.5% monozygotic (MZ)) and 404 AA (178 twin
      pairs, 42.7% MZ) women at baseline (T1; median age 15 years) and 3,225 EA (1,511
      twin pairs, 55.3% MZ) and 539 AA (252 pairs, 43.3% MZ) women at follow-up (T2;
      median age 22 years) from a Midwestern US, population-based twin registry were
      used to construct biometrical genetic models. For EA women, the majority of the
      variance in BMI was attributable to additive genetic effects at both time points
      (82% for each), with the remaining variance attributable to nonshared
      environment. Genetic and nonshared environment correlations between adolescent
      and young adult BMI were 0.87 and 0.23, respectively. Among AA women, nonadditive
      genetic effects comprised 68% of the variance at T1 and 73% at T2, and were
      highly correlated (r(D) = 0.94). The proportions of variance attributable to
      nonshared environment at T1 (29%) and T2 (25%) were more modestly correlated
      (r(E) = 0.31). The remaining variance in AA women could be attributed to additive
      genetic effects. Additive vs. nonadditive genetic effects contribute
      differentially to BMI in AA vs. EA adolescent and young adult women. Additional
      research is needed to better characterize the environmental and genetic factors
      related to BMI in persons of different races to aid understanding of the complex
      determinants of body weight in individuals.

PMID- 19165160
TI  - Neurobehavioral inhibition of reward-driven feeding: implications for dieting and
      obesity.

PMID- 19165161
TI  - The stigma of obesity: a review and update.

PMID- 19165162
TI  - Development of overweight in children in relation to parental weight and
      socioeconomic status.
AB  - The purpose of the study was to test the hypothesis that socioeconomic status
      (SES) moderates the association between parental weight and changes in BMI from
      childhood to early adolescence. Participants included 428 twin children from 100
      families with obese parents ("obese families") and 114 sociodemographically
      matched families with normal-weight parents ("lean families") who were assessed
      in their homes (age = 4.4). Follow-up study was conducted 7 years later (age =
      11.2) on 346 children (81%). Complete data were available for 333 children.
      Family SES was indexed with maternal education. Children's weights and heights
      were measured to calculate BMI s.d. scores based on 1990 British norms.
      Overweight was defined as >91st BMI centile. In children with obese parents, BMI
      s.d. scores increased from 0.51 at age 4 to 1.06 at age 11. In children with lean
      parents, BMI s.d. scores decreased from 0.11 to 0.05. Prevalence of overweight
      remained stable from age 4 to 11 in children with lean parents (8% to 9%), but it
      more than doubled in children with obese parents (17% to 45%). There was a
      significant interaction between parental weight and family SES (P < 0.01), so
      that in children with lean parents there was no SES difference in the BMI status
      from age 4 to 11; however, in children with obese parents, the increase in
      adiposity was significantly greater in lower SES families. These results suggest
      that parental leanness confers significant protection against development of
      overweight in children regardless of family SES, while parental obesity is an
      adverse prognostic sign, especially in lower SES families.

PMID- 19165163
TI  - Association studies on ghrelin and ghrelin receptor gene polymorphisms with
      obesity.
AB  - Ghrelin exerts a stimulatory effect on appetite and regulates energy homeostasis.
      Ghrelin gene variants have been shown to be associated with metabolic traits,
      although there is evidence suggesting linkage and association with obesity and
      the ghrelin receptor (GHSR). We hypothesized that these genes are good candidates
      for susceptibility to obesity. Direct sequencing identified 12 ghrelin single
      nucleotide polymorphisms (SNPs) and 8 GHSR SNPs. The 10 common SNPs were
      genotyped in 1,275 obese subjects and in 1,059 subjects from a general population
      cohort of European origin. In the obesity case-control study, the GHSR SNP
      rs572169 was found to be associated with obesity (P = 0.007 in additive model, P
      = 0.001 in dominant model, odds ratio (OR) 1.73, 95% confidence interval (1.23
      2.44)). The ghrelin variant, g.A265T (rs4684677), showed an association with
      obesity (P = 0.009, BMI adjusted for age and sex) in obese families. The ghrelin
      variant, g.A-604G (rs27647), showed an association with insulin levels at 2-h
      post-oral glucose tolerance test (OGTT) (P = 0.009) in obese families. We found
      an association between the eating behavior "overeating" and the GHSR SNP
      rs2232169 (P = 0.02) in obese subjects. However, none of these associations
      remained significant when corrected for multiple comparisons. Replication of the
      nominal associations with obesity could not be confirmed in a German genome-wide
      association (GWA) study for rs4684677 and rs572169 polymorphisms. Our data
      suggest that common polymorphisms in ghrelin and its receptor genes are not major
      contributors to the development of polygenic obesity, although common variants
      may alter body weight and eating behavior and contribute to insulin resistance,
      in particular in the context of early-onset obesity.

PMID- 19165164
TI  - Transcriptional control of human adipose tissue blood flow.
AB  - Adipose tissue is highly vascularized and expresses several genes involved in
      vasodilatory and vasoconstrictive regulation. We took a transcriptional approach
      to study the relationships between adipose tissue blood flow (ATBF) and genes
      involved in vasoactive processes. As ATBF is impaired in obesity, we tested
      whether body weight interfered with the transcriptional regulation of ATBF. The
      mRNA content (real-time PCR) of 26 genes was quantified in subcutaneous adipose
      tissue biopsies from 28 healthy men with a wide range of BMI. ATBF was measured
      by 133Xe washout. None of the transcripts was related to fasting ATBF (ATBFF).
      However, the expression levels of two transcripts involved in vasodilation
      (natriuretic peptide receptor A/guanylate cyclase A (NPRA) and endothelial nitric
      oxide synthase (eNOS)) were positively associated with postprandial ATBF (r =
      0.53 and r = 0.55, P < 0.01, respectively). Although BMI was negatively related
      to the mRNA content of NPRA and eNOS (r = -0.78 and r = -0.63, P < 0.01,
      respectively), the strong associations found between postprandial ATBF and the
      two transcripts were not affected by obesity. Several genes were subject to
      coordinated regulation of expression. This study demonstrates for the first time
      that ATBF responsiveness to nutrient intake is related to the transcription of
      two genes expressed in adipose tissue and directly involved in vasodilatory
      actions (eNOS and NPRA), suggesting that part of the regulation of ATBF is at a
      transcriptional level. Interestingly, these associations were not secondary to
      changes in BMI. We also found that certain genes involved in the regulation of
      ATBF are subject to coordinate regulation of expression suggesting physiological
      autoregulation.

PMID- 19165165
TI  - Smoking kills, obesity disables: a multistate approach of the US Health and
      Retirement Survey.
AB  - Increasing BMI causes concerns about the consequences for health care. Decreasing
      cardiovascular mortality has lowered obesity-related mortality, extending
      duration of disability. We hypothesized increased duration of disability among
      overweight and obese individuals. We estimated age-, risk-, and state-dependent
      probabilities of activities of daily living (ADL) disability and death and
      calculated multistate life tables, resulting in the comprehensive measure of life
      years with and without ADL disability. We used prospective data of 16,176 white
      adults of the Health and Retirement Survey (HRS). Exposures were self-reported
      BMI and for comparison smoking status and levels of education. Outcomes were
      years to live with and without ADL disability at age 55. The reference categories
      were high normal weight (BMI: 23-24.9), nonsmoking and high education. Mild
      obesity (BMI: 30-34.9) did not change total life expectancy (LE) but exchanged
      disabled for disability-free years. Mild obesity decreased disability-free LE
      with 2.7 (95% confidence limits 1.2; 3.2) year but increased LE with disability
      with 2.0 (0.6; 3.4) years among men. Among women, BMI of 30 to 34.9 decreased
      disability-free LE with 3.6 (2.1; 5.1) year but increased LE with disability with
      3.2 (1.6;4.8) years. Overweight (BMI: 25-29.9) increases LE with disability for
      women only, by 2.1 (0.8; 3.3) years). Smoking compressed disability by high
      mortality. Smoking decreased LE with 7.2 years, and LE with disability with 1.3
      (0.5; 2.5) years (men) and 1.4 (0.3; 2.6) years (women). A lower education
      decreased disability-free life, but not duration of ADL disability. In the aging
      baby boom, higher BMI will further increase care dependence.

PMID- 19165167
TI  - Pre- and postsurgery behavioral compliance, patient health, and postbariatric
      surgical weight loss.
AB  - This study investigated the relationship between weight loss from gastric bypass
      surgery, patient characteristics, and compliance with physician instructions
      before and after surgery. A chart review of psychiatric and medical files was
      conducted for an initial cohort of 172 patients in a postsurgical management
      program. A total of 112 patients (primarily women (85%), white (79%), and well
      educated) from this cohort had presurgical data. Of these 112 subjects, 67 (60%)
      had postsurgical compliance information and BMI at 24 months postsurgery. The
      relationships between weight loss and a number of demographic, psychiatric,
      comorbid, and behavioral compliance factors were examined for these 67 patients.
      Missed appointments and noncompliance with exercise and weight loss plan
      instructions were high before and after surgery (65% vs. 72% for missed
      appointments, 39% vs. 51% for exercise, 42% vs. 57% for weight loss
      instructions). Although poor food choices were not frequently a problem before
      surgery (11%), they increased significantly after surgery: 37%, chi(2)(1) =
      25.00, P < 0.001. Participants who lost the least weight at 2 years postsurgery
      were more likely to be nonwhite (r = 0.27, P = 0.039), have a lower socioeconomic
      status (SES) (r = 0.285, P = 0.02), and have a diagnosis of binge eating before
      surgery (r = 0.25, P = 0.039). Having more contact with patients and requiring
      adherence to behavioral changes, especially with respect to exercise and dietary
      restrictions, may improve the long-term outcomes for bariatric procedures. In
      addition, those patients who are depressed and suffer from binge eating may need
      special attention from physicians during long-term postoperative follow-up.

PMID- 19165166
TI  - Waist circumference measurement by site, posture, respiratory phase, and meal
      time: implications for methodology.
AB  - Waist circumference (WC) has been advocated as a simple, reliable, and cost
      effective measure to understand an individual's cardio-metabolic risk. Although
      several protocols exist for measuring WC, the variation induced by a few factors
      has not been investigated. We compared several established and experimental WC
      measurement protocols to identify factors that may cause variations in WC
      measurement. In this cross-sectional study, we examined the variations in the
      measurement of waist circumference (WC) measures carried out in 11 ways differing
      by anatomical site, posture, respiratory phase, and time since last meal, using
      repeated measure analysis of variance (using mixed models) after Tukey-Kramer
      adjustment. We estimated the proportion of variance in percentage of body fat
      (%BF) and fat-free mass (FFM) explained by each of the WC measures. We studied
      123 apparently healthy Asian Indians (75 females), with mean (s.d.) age of 34
      (8.7) years and BMI of 23.9 (4.8) kg/m(2). Overall, the mean of WCs measured
      using the 11 protocols were statistically different. Further, post hoc analysis
      showed statistically significant, yet mostly small, differences between most of
      the pairs. No single WC measure explained highest variance in %BF or FFM for both
      genders. Although, the National Institute of Health (NIH), USA, protocol was
      convenient and may be less prone to errors, at present it does not control for
      many variables tested in this study. Measures of WC measured using different
      protocols were statistically different. We suggest that the site of measurement,
      posture, phase of respiration, and time since last meal should be standardized
      for the development of a protocol for measurement of WC for worldwide use.

PMID- 19165168
TI  - Proteasome subunits mRNA expressions correlate with male BMI: implications for a
      role in obesity.
AB  - Obesity as well as its associated chronic diseases and adverse health
      consequences such as type 2 diabetes mellitus, dyslipidemia, hypertension, and
      coronary artery disease are afflicting middle-aged adults and an ever greater
      number of children globally. We planned to investigate new obesity-related
      factors using proteomics approaches in a randomly selected three high and three
      low BMI samples of Epstein-Barr-transformed B (EBV-B) lymphoblastoid cell lines
      prepared from two groups of young Japanese men with different BMI. To search
      novel obesity-related factors, comparisons of protein expressions between high
      and low BMI groups were carried out by two-dimensional gel electrophoresis (2
      DE). Gene transcripts of proteasome subunits found out from 2-DE were further
      determined by quantitative real-time PCR. Results from proteomics approach showed
      that the expression of proteasome alpha subunit type 5 (PSMA5) was significantly
      lower in the high BMI male group than in those with low BMI (P < 0.05). To
      validate these results, we expanded the study to include 20 more men and used
      real-time PCR to quantify the mRNA expression level in their EBV-B cells. Both
      PSMA5 and PSMA2 of EBV-B cells showed negative correlation with BMI. Furthermore,
      the mRNA levels measured in the peripheral blood B lymphocytes for many
      proteasome subunits in 75 healthy men and women showed significant negative
      correlation with BMI in healthy men. Our findings suggest that proteasome
      expression may play a key role in obesity.

PMID- 19165170
TI  - A longitudinal study of sedentary behavior and overweight in adolescent girls.
AB  - The aim of this study is to examine sedentary and light activity in relation to
      overweight in adolescent girls. Adolescent girls were randomly recruited from 36
      schools participating in the Trial of Activity for Adolescent Girls (TAAG).
      Assessments included age, ethnicity, socioeconomic status, and body composition
      estimated from weight, height, and triceps skinfold. Sedentary and light activity
      was measured for 6 days using accelerometry in 6th and in 8th grade among two
      randomly sampled cross-sections of girls. Sedentary activity increased from the
      6th to 8th grade by 51.5 min/day. In the 8th grade, a significantly higher number
      of hours in sedentary activity for each of the 6-days of measurement were evident
      with higher tertiles of percent body fat (30-35%, >35% fat) (P < 0.05), but not
      across all increasing tertiles of BMI (5th to 85th, 85th to 95th, and >95th
      percentiles). The increase in sedentary activity was observed on weekdays, but
      not on weekends for percent body fat tertiles. In the cohort of girls measured in
      both 6th and 8th grades, the mean cross-sectional coefficient estimates were
      significant for percent body fat, but not BMI for sedentary and light activities.
      Adolescent girls from the 6th to 8th grade are shifting their time from light to
      more sedentary activity as measured by accelerometers. In addition, the increase
      in sedentary activity is not associated with an adverse effect on BMI or percent
      body fat. The eventual impact of this shift to a more sedentary lifestyle on body
      composition and other outcomes needs to be evaluated further.

PMID- 19165169
TI  - Variants in the CNR1 and the FAAH genes and adiposity traits in the community.
AB  - Pharmacologic blockade of the endocannabinoid receptor 1 leads to weight loss and
      an improved metabolic risk profile in overweight and obese individuals. We
      hypothesize that common genetic variants in the CNR1 (encoding endocannabinoid
      receptor 1) and FAAH genes (encoding fatty acid amide hydrolase, a key enzyme
      hydrolyzing endocannabinoids) are associated with adiposity traits. We genotyped
      18 single-nucleotide polymorphisms (SNPs) in the CNR1 gene and 9 SNPs in the FAAH
      gene in 2,415 Framingham Offspring Study participants (mean age 61 +/- 10 years;
      52.6% women; mean BMI 28.2 +/- 5.4 kg/m(2); 30.3% obese) and studied them for
      association with cross-sectional and longitudinal measures of adiposity (BMI,
      waist circumference, change over time in BMI and waist circumference, visceral
      and subcutaneous adipose tissue) using linear mixed-effect models. The selected
      SNPs captured 85% (r(2) = 0.8) of the common variation (minor allele frequency
      >5%) at the CNR1 locus and 96% (r(2) = 0.8) of the common variation at the FAAH
      locus (defined as the genomic segment containing the gene +20 kb upstream and +10
      kb downstream). After correction for multiple testing, none of the SNPs in the
      CNR1 gene or in the FAAH gene displayed statistical evidence for association with
      BMI, waist circumference, and visceral adipose tissue or subcutaneous adipose
      tissue (all P > 0.18). Despite comprehensive SNP mapping across the genes and
      their regulatory regions in a large unselected sample, we failed to find evidence
      for an association of common variants in the CNR1 and FAAH genes with measures of
      adiposity in our community-based sample.

PMID- 19165171
TI  - Liver NF-kappaB and AP-1 DNA binding in obese patients.
AB  - Oxidative stress and insulin resistance (IR) are major contributors in the
      pathogenesis of nonalcoholic fatty liver disease (NAFLD) and in the progression
      from steatosis to nonalcoholic steatohepatitis (NASH). Our aim was to assess
      nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) activation and
      Toll-like receptor 4 (TLR4) expression as signaling mechanisms related to liver
      injury in obese NAFLD patients, and examined potential correlations among them,
      oxidative stress, and IR. Liver NF-kappaB and AP-1 (electromobility shift assay
      (EMSA)), TLR4 expression (western blot), ferric reducing ability of plasma
      (FRAP), and IR evolution (HOMA) were evaluated in 17 obese patients who underwent
      subtotal gastrectomy with gastro-jejunal anastomosis in Roux-en-Y and 10 nonobese
      subjects who underwent laparoscopic cholecystectomy (controls). Liver NF-kappaB
      and AP-1 DNA binding were markedly increased in NASH patients (n = 9; P < 0.05)
      compared to controls, without significant changes in NAFLD patients with
      steatosis (n = 8), whereas TLR4 expression was comparable between groups. Hepatic
      NF-kappaB activation was positively correlated with that of AP-1 (r = 0.79; P <
      0.0001); both liver NF-kappaB and AP-1 DNA binding were inversely associated with
      FRAP (r = -0.43 and r = -0.40, respectively; P < 0.05) and directly correlated
      with HOMA (r = 0.66 and r = 0.62, respectively, P < 0.001). Data presented show
      enhanced liver activation of the proinflammatory transcription factors NF-kappaB
      and AP-1 in obese patients with NASH, parameters that are significantly
      associated to oxidative stress and IR.

PMID- 19165173
TI  - Light chain proximal tubulopathy.

PMID- 19165172
TI  - Dieting frequency in obese patients with binge eating disorder: behavioral and
      metabolic correlates.
AB  - This study examined the clinical significance of self-reported frequency of time
      spent dieting in obese patients with binge eating disorder (BED). A total of 207
      treatment-seeking obese BED patients (57 men and 150 women) were dichotomized by
      dieting frequency and gender and compared on a number of historical,
      psychological, and metabolic variables. Frequent dieters reported significantly
      earlier age of onset for binge eating, dieting, and obesity, more episodes of
      weight cycling, greater weight suppression, and greater eating disorder pathology
      than infrequent dieters; no differences, however, emerged on current binge eating
      frequency or psychological distress. Among women but not among men, frequent
      dieters had consistently lower chances of abnormalities in total cholesterol,
      high-density lipoprotein (HDL) cholesterol, and the total/HDL cholesterol ratio
      while infrequent dieters had greater chances of abnormalities on these variables.
      Dietary restraint was inversely correlated with abnormalities in triglycerides,
      HDL cholesterol, and the total/HDL cholesterol ratio but was unrelated to low
      density lipoprotein (LDL) cholesterol. In summary, frequent dieters of both
      genders had greater lifetime and current eating and weight concerns, and in
      women, decreased chance of metabolic abnormalities than infrequent dieters. Our
      findings suggest that frequent dieting attempts, particularly in women, are
      associated with greater eating disorder pathology but may have a beneficial
      effect on metabolic functioning and cardiovascular disease risk independent of
      actual weight status. These findings may have implications for clinical advice
      provided to obese BED patients.

PMID- 19165174
TI  - Activation of A(2) adenosine receptors dilates cortical efferent arterioles in
      mouse.
AB  - Adenosine can induce vasodilatation and vasoconstriction of the renal afferent
      arteriole of the mouse. We determined here its direct effect on efferent
      arterioles of mouse kidneys. Using isolated-perfused cortical efferent
      arterioles, we measured changes in luminal diameter in response to adenosine.
      Extraluminal application of adenosine and cyclohexyladenosine had no effect on
      the luminal diameter. When the vessels were constricted by the thromboxane
      mimetic U46619, application of adenosine and 5'-N-ethylcarboxamido-adenosine
      dilated the efferent arterioles in a dose-dependent manner. We also found that
      the adenosine-induced vasodilatation was inhibited by the A(2)-specific receptor
      blocker 3,7-dimethyl-1-propargylxanthine. In the presence of this inhibitor,
      adenosine failed to alter the basal vessel diameter of quiescent efferent
      arterioles. Using primer-specific polymerase chain reaction we found that the
      adenosine A(1), A(2a), A(2b), and A(3) receptors were expressed in microdissected
      mouse efferent arterioles. We conclude that adenosine dilates the efferent
      arteriole using the A(2) receptor subtype at concentrations compatible with
      activation of the A(2b) receptor.

PMID- 19165175
TI  - Uremic cardiac hypertrophy is reversed by rapamycin but not by lowering of blood
      pressure.
AB  - Chronic kidney disease is often complicated by uremic cardiomyopathy that
      consists of left ventricular hypertrophy and interstitial fibrosis. It is thought
      that hypertension and volume overload are major causes of this disease, but here
      we sought to identify additional mechanisms using a mouse model of chronic renal
      insufficiency. Mice with a remnant kidney developed an elevated blood urea
      nitrogen by 1 week, as expected, and showed progressive cardiac hypertrophy and
      fibrosis at 4 and 8 weeks even though their blood pressures were not elevated nor
      did they show signs of volume overload. Cardiac extracellular signal-regulated
      kinase (ERK) was activated in the uremic animals at 8 weeks. There was also an
      increased phosphorylation of S6 kinase, which is often mediated by activation of
      the mammalian target of rapamycin (mTOR). To test the involvement of this
      pathway, we treated these uremic mice with rapamycin and found that it reduced
      cardiac hypertrophy. Reduction of blood pressure, however, by hydralazine had no
      effect. These studies suggest that uremic cardiomyopathy is mediated by
      activation of a pathway that involves the mTOR pathway.

PMID- 19165176
TI  - Nonrenal regulation of EPO synthesis.
AB  - Erythropoietin (EPO) is a circulating glycoprotein hormone whose principal
      function is thought to be red blood cell production. It is a classic example of a
      hypoxia-inducible gene, and studies of the induction of EPO synthesis by low
      oxygen led to the discovery of a widespread system of hypoxia-inducible
      transcription factors. Tissue-specific expression of the EPO gene is tightly
      controlled, and in the adult organism the kidney produces around 90% of systemic
      EPO. Before birth, the liver is the main site of EPO production; factors
      contributing to the liver-to-kidney switch are still elusive, but may provide
      clues to the tissue-specificity of EPO gene expression. EPO has also been
      detected in non-erythropoietic tissues such as the brain, where it is suggested
      to exert local protective effects. Apart from classical ways of regulating renal
      EPO during hypoxia and anemia, novel pathways have been discovered that
      demonstrate that other organ systems in the adult might not only be important for
      the production of EPO but also for modulating the hypoxic EPO response. Knowledge
      of the molecular bases of these non-renal pathways will eventually help to
      develop pharmacological strategies to induce endogenous EPO production when the
      main source, the kidney, is significantly impaired. This review will provide an
      overview of the molecular aspects of EPO gene regulation by hypoxia-inducible
      transcription factors and of the tissue-specific regulation of EPO production in
      adult mammals. Insights into the biology of EPO production in genetically
      modified animals, with an emphasis on recent advances in the understanding of non
      renal EPO regulation, will be discussed.

PMID- 19165177
TI  - Periodontal disease adversely affects the survival of patients with end-stage
      renal disease.
AB  - Periodontal disease is associated with cardiovascular disease and is thought to
      accelerate systemic atherosclerosis. Here we examined the relationship between
      periodontitis and cardiovascular disease mortality in outpatients on hemodialysis
      using a retrospective analysis of 168 adult patients in New York City and North
      Carolina. During 18 months of follow-up, cardiovascular disease and all-cause
      mortality were determined from a centralized dialysis registry. One hundred
      patients had mild or no periodontal disease but the remaining 68 had moderate-to
      severe disease defined as 2 or more teeth with at least 6 mm of inter-proximal
      attachment loss. At baseline, the proportion of males was significantly lower in
      the moderate-to-severe group. Compared with mild or no periodontal disease,
      moderate-to-severe disease was significantly associated with death from
      cardiovascular causes. Adjustment for age, gender, center and dialysis vintage,
      smoking status, and history of diabetes mellitus or hypertension did not diminish
      the strength of this association. Our findings suggest a need for larger studies
      to confirm this connection, along with intervention trials to determine if
      treating periodontitis reduces cardiovascular disease mortality in dialysis
      patients.

PMID- 19165180
TI  - Bacterial infection may limit spread of dengue fever.

PMID- 19165178
TI  - Incompletely penetrant PKD1 alleles suggest a role for gene dosage in cyst
      initiation in polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) caused by mutations in PKD1
      is significantly more severe than PKD2. Typically, ADPKD presents in adulthood
      but is rarely diagnosed in utero with enlarged, echogenic kidneys. Somatic
      mutations are thought crucial for cyst development, but gene dosage is also
      important since animal models with hypomorphic alleles develop cysts, but are
      viable as homozygotes. We screened for mutations in PKD1 and PKD2 in two
      consanguineous families and found PKD1 missense variants predicted to be
      pathogenic. In one family, two siblings homozygous for R3277C developed end stage
      renal disease at ages 75 and 62 years, while six heterozygotes had few cysts. In
      the other family, the father and two children with moderate to severe disease
      were homozygous for N3188S. In both families homozygous disease was associated
      with small cysts of relatively uniform size while marked cyst heterogeneity is
      typical of ADPKD. In another family, one patient diagnosed in childhood was found
      to be a compound heterozygote for the PKD1 variants R3105W and R2765C. All three
      families had evidence of developmental defects of the collecting system. Three
      additional ADPKD families with in utero onset had a truncating mutation in trans
      with either R3277C or R2765C. These cases suggest the presence of incompletely
      penetrant PKD1 alleles. The alleles alone may result in mild cystic disease; two
      such alleles cause typical to severe disease; and, in combination with an
      inactivating allele, are associated with early onset disease. Our study indicates
      that the dosage of functional PKD1 protein may be critical for cyst initiation.

PMID- 19165181
TI  - Bees may enjoy coke.

PMID- 19165185
TI  - Protocol deviations revisited.

PMID- 19165186
TI  - Reportability of protocol suspensions.

PMID- 19165187
TI  - Reportability of protocol suspensions. Report may vary.

PMID- 19165188
TI  - Reportability of protocol suspensions. A word from OLAW and USDA.

PMID- 19165189
TI  - Response to Protocol Review Scenario: Report a suspension.

PMID- 19165190
TI  - What's your diagnosis. Tail mass in a mouse. Cutaneous hemangiosarcoma.

PMID- 19165192
TI  - Management of aquatic turtle shell fractures.
AB  - In a previous column, the author discussed the overall management of turtle shell
      injuries. This column continues by describing basic techniques for repairing and
      stabilizing fractured turtle shells.

PMID- 19165193
TI  - Insights into modeling streptozotocin-induced diabetes in ICR mice.
AB  - Streptozotocin (STZ)-induced diabetes in ICR mice is often used to model diabetes
      mellitus and its complications, as well as other pathologies. In studies of
      diabetes progression and effects of newly developed treatments, experimental
      results may be difficult to interpret because blood glucose levels (BGLs) of
      untreated diabetic control animals tend to decline substantially during typical
      experimental time spans of 8-11 h. To address this problem, the authors examined
      several experimental conditions that might affect BGL stability, including STZ
      dose, initial mouse weight, fasting regimen and light:dark cycle. The authors
      found that diabetes severity was dependent on initial mouse weight and that
      weight loss after diabetes induction was less severe in heavier mice.
      Furthermore, a dose of 150 mg STZ per kg body weight was sufficient to induce
      stabilized acute diabetes without causing many complications. Finally, BGL could
      be stabilized in diabetic mice that were not treated with insulin by avoiding pre
      fasting before an 8-h experiment and by allowing mice limited access to food
      during the experiment.

PMID- 19165194
TI  - Effects of a fire alarm strobe light on fecal corticosterone metabolite
      concentrations in mice.
AB  - The type and location of fire alarms are important considerations in animal
      facility design. The Guide for the Care and Use of Laboratory Animals recommends
      minimizing animal exposure to such alarms. Nevertheless, it is often necessary to
      maintain fire alarms within animal housing or procedural areas. The authors
      exposed male mice to the flashing strobe light component of a standard fire alarm
      and evaluated mouse fecal corticosterone concentration, which is known to be an
      indicator of stress. Mice were exposed to the strobe light for 5 min during
      either the light or the dark phase of the light:dark cycle. The authors collected
      fecal samples every 6 h for 24 h before exposing mice to the alarm and every 6 h
      for 24 h after exposure. Fecal samples taken before exposure (baseline samples)
      showed a normal circadian pattern of corticosterone metabolite excretion. In
      fecal samples taken after mice were exposed to the fire alarm, metabolite
      concentrations did not significantly differ from baseline concentrations over
      time.

PMID- 19165195
TI  - Diversity in the lab.

PMID- 19165196
TI  - Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or
      without cetuximab in the MRC COIN trial experience.
AB  - We present the preliminary toxicity data from the MRC COIN trial, a phase III
      randomised controlled trial of first-line therapy in advanced colorectal cancer,
      with particular reference to the addition of cetuximab to an oxaliplatin
      fluoropyrimidine combination. A total of 804 patients were randomised between
      March 2005 and July 2006 from 78 centres throughout the United Kingdom. Patients
      were allocated to oxaliplatin plus fluoropyrimidine chemotherapy with or without
      the addition of weekly cetuximab. The choice of fluoropyrimidine (either 5
      fluorouracil (5FU) or capecitabine) was decided by the treating physician and
      patient before randomisation. Toxicity data were collected from all patients. Two
      hundred and three patients received 5FU plus oxaliplatin (OxMdG, 25%), 333
      oxaliplatin+capecitabine (Xelox, 41%), 102 received OxMdG+cetuximab (OxMdG+C,
      13%) and 166 Xelox+cetuximab (21%). Percent grade 3/4 toxicities included
      diarrhoea 6, 15, 13 and 25%, nausea/vomiting 3, 7, 7 and 14% for OxMdG, Xelox,
      OxMdG+C and Xelox+C, respectively. Sixty-day all-cause mortality was 6, 5, 5 and
      7%. Statistically significant differences were evident for patients receiving
      Xelox+cetuximab vs Xelox alone: diarrhoea relative risk (RR) 1.69 (1.17, 2.43,
      P=0.005) and nausea/vomiting RR 2.01 (1.16, 3.47, P=0.012). The excess toxicity
      observed in the oxaliplatin-, capecitabine-, cetuximab-treated patients led the
      trial management group to conclude that a capecitabine dose adjustment was
      required to maintain safety levels when using this regimen.

PMID- 19165197
TI  - Deficient mismatch repair system in patients with sporadic advanced colorectal
      cancer.
AB  - A deficient mismatch repair system (dMMR) is present in 10-20% of patients with
      sporadic colorectal cancer (CRC) and is associated with a favourable prognosis in
      early stage disease. Data on patients with advanced disease are scarce. Our aim
      was to investigate the incidence and outcome of sporadic dMMR in advanced CRC.
      Data were collected from a phase III study in 820 advanced CRC patients.
      Expression of mismatch repair proteins was examined by immunohistochemistry. In
      addition microsatellite instability analysis was performed and the methylation
      status of the MLH1 promoter was assessed. We then correlated MMR status to
      clinical outcome. Deficient mismatch repair was found in only 18 (3.5%) out of
      515 evaluable patients, of which 13 were caused by hypermethylation of the MLH1
      promoter. The median overall survival in proficient MMR (pMMR), dMMR caused by
      hypermethylation of the MLH1 promoter and total dMMR was 17.9 months (95%
      confidence interval 16.2-18.8), 7.4 months (95% CI 3.7-16.9) and 10.2 months (95%
      CI 5.9-19.8), respectively. The disease control rate in pMMR and dMMR patients
      was 83% (95% CI 79-86%) and 56% (30-80%), respectively. We conclude that dMMR is
      rare in patients with sporadic advanced CRC. This supports the hypothesis that
      dMMR tumours have a reduced metastatic potential, as is observed in dMMR patients
      with early stage disease. The low incidence of dMMR does not allow drawing
      meaningful conclusions about the outcome of treatment in these patients.

PMID- 19165198
TI  - A randomised pilot Phase II study of doxorubicin and cyclophosphamide (AC) or
      epirubicin and cyclophosphamide (EC) given 2 weekly with pegfilgrastim
      (accelerated) vs 3 weekly (standard) for women with early breast cancer.
AB  - Accelerated (dose-dense) chemotherapy, in which the frequency of administration
      is increased without changing total dose or duration, may increase the efficacy
      of cancer chemotherapy. We performed a randomised Phase II study to assess the
      safety and relative toxicity of AC (doxorubicin; cyclophosphamide) vs
      E(epirubicin)C given by conventional or accelerated schedules as neoadjuvant or
      adjuvant chemotherapy for early breast cancer. Furthermore, the relative toxicity
      of doxorubicin and epirubicin remains uncertain. Patients were randomised to one
      of four arms; four courses of standard 3 weekly cyclophosphamide 600 mg m(-2) in
      combination with doxorubicin 60 mg m(-2) (AC) vs epirubicin 90 mg m(-2) (EC) 3
      weekly vs the same regimens administered every 2 weeks with pegfilgrastim (G
      CSF). A total of 126 patients were treated, 42 with standard AC, 42 with
      accelerated AC, 19 with standard EC and 23 with accelerated EC. Significantly
      more grade 3/4 day one neutropenia was seen with standard (6/61, 10%) compared to
      accelerated (0/65,) regimens (P=0.01). A trend towards more neutropenic sepsis
      was seen in the combined standard and accelerated AC arms (12/84, 14%) compared
      to the combined EC arms (1/42, 2%), P=0.06. Falls in left ventricular ejection
      fraction were not increased with accelerated treatment. Accelerated AC and EC
      with pegfilgrastim are safe and feasible regimens in the treatment of early
      breast cancer with less neutropenia than conventional 3 weekly schedules.

PMID- 19165199
TI  - Direct effects of doxorubicin on skeletal muscle contribute to fatigue.
AB  - Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has
      been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In
      this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin
      induced impaired ex vivo skeletal muscle relaxation followed in time by
      contraction impediment, which could be explained by DOX-induced changes in Ca(2+)
      responses of myotubes in vitro. The Ca(2+) responses in skeletal muscle, however,
      could not be explained by oxidative stress.

PMID- 19165200
TI  - A humanised anti-IGF-1R monoclonal antibody (AVE1642) enhances Bortezomib-induced
      apoptosis in myeloma cells lacking CD45.
AB  - The humanised form of an antagonistic anti-IGF-1R mAb (AVE1642) selectively
      inhibits the growth of CD45(neg) myeloma cells. AVE1642 strongly increased
      bortezomib-induced apoptosis, correlated with an increase of Noxa expression.
      These results support the therapeutic use of anti-IGF-1R/bortezomib in CD45(neg)
      Myeloma patients, particularly those with the most aggressive form, t(4,14).

PMID- 19165201
TI  - LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased
      sensitivity to MAPK and mTOR signalling inhibition.
AB  - LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating
      mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer
      syndrome. It is also somatically inactivated in approximately 30% of non-small
      cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines
      are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in
      proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar
      sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR
      inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs
      are a genetically and functionally distinct subset and further suggest that this
      subset of lung cancers might afford an opportunity for exploitation of anti
      MAPK/mTOR-targeted therapies.

PMID- 19165202
TI  - RASSF1A hypermethylation in pretreatment serum DNA of neuroblastoma patients: a
      prognostic marker.
AB  - The tumour suppressor gene RASSF1A is known to be frequently silenced by promoter
      hypermethylation in neuroblastoma tumours. Here we explored the possible
      prognostic significance of aberrant promoter hypermethylation of RASSF1A in serum
      DNA samples of patients with neuroblastoma as a surrogate marker for circulating
      tumour cells. We analysed the methylation status of the RASSF1A gene in matched
      tumour and pretreatment serum DNA obtained from 68 neuroblastoma patients.
      Hypermethylation of RASSF1A in tumour samples was found in 64 patients (94%). In
      contrast, serum methylation of RASSF1A was observed in 17 patients (25%). Serum
      methylation of RASSF1A was found to be statistically associated with age > or =12
      months at diagnosis (P=0.002), stage 4 (P<0.001) and MYCN amplification
      (P<0.001). The influence of serum RASSF1A methylation on prognosis was found to
      be comparable with that of the currently most reliable marker, MYCN amplification
      on univariate analysis (hazard ratio, 9.2; 95% confidence interval (CI), 2.8
      30.1; P<0.001). In multivariate analysis of survival, methylation of RASSF1A in
      serum had a hazard ratio of 2.4 (95% CI, 0.6-9.2), although this association did
      not reach statistical significance (P=0.194). These findings show that the
      methylation status of RASSF1A in the serum of patients with neuroblastoma has the
      potential to become a prognostic predictor of outcome.

PMID- 19165204
TI  - A pledge for immediate action.
AB  - Drastic measures aimed at reducing carbon emissions must be taken now to avoid
      the devastating effects of global warming on our future.

PMID- 19165203
TI  - The key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours
      and is associated with resistance to chemotherapy.
AB  - Basal-like tumours account for 15% of invasive breast carcinomas and are
      associated with a poorer prognosis and resistance to therapy. We hypothesised
      that this aggressive phenotype is because of an intrinsically elevated hypoxic
      response. Microarrayed tumours from 188 patients were stained for hypoxia
      inducible factor (HIF)-1alpha, prolyl hydroxylase (PHD)1, PHD2, PHD3 and factor
      inhibiting HIF (FIH)-1, and carbonic anhydrase (CA) IX stained in 456 breast
      tumours. Tumour subtypes were correlated with standard clincopathological
      parameters as well as hypoxic markers. Out of 456 tumours 62 (14%) tumours were
      basal-like. These tumours were positively correlated with high tumour grade
      (P<0.001) and were associated with a significantly worse disease-free survival
      compared with luminal tumours (P<0.001). Fifty percent of basal-like tumours
      expressed HIF-1alpha, and more than half expressed at least one of the PHD
      enzymes and FIH-1. Basal-like tumours were nine times more likely to be
      associated with CAIX expression (P<0.001) in a multivariate analysis. Carbonic
      anhydrase IX expression was positively correlated with tumour size (P=0.005),
      tumour grade (P<0.001) and oestrogen receptor (ER) negativity (P<0.001). Patients
      with any CAIX-positive breast tumour phenotype and in the basal tumour group had
      a significantly worse prognosis than CAIX-negative tumours when treated with
      chemotherapy (P<0.001 and P=0.03, respectively). The association between basal
      phenotype and CAIX suggests that the more aggressive behaviour of these tumours
      is partly due to an enhanced hypoxic response. Further, the association with
      chemoresistance in CAIX-positive breast tumours and basal-like tumours in
      particular raises the possibility that targeted therapy against HIF pathway or
      downstream genes such as CAs may be an approach to investigate for these
      patients.

PMID- 19165205
TI  - An inconvenient truth about thermoelectrics.
AB  - Despite recent advances, thermoelectric energy conversion will never be as
      efficient as steam engines. That means thermoelectrics will remain limited to
      applications served poorly or not at all by existing technology. Bad news for
      thermoelectricians, but the climate crisis requires that we face bad news head
      on.

PMID- 19165207
TI  - Nanocatalysis: More than speed.

PMID- 19165208
TI  - Mixed conductors: The bridge to redox switches.

PMID- 19165209
TI  - Polymer self-assembly: Micelles make a living.

PMID- 19165210
TI  - Spintronics: Organics strike back.

PMID- 19165211
TI  - Material witness: What's philosophy got to do with it?

PMID- 19165213
TI  - Molecular mechanisms of proteasome assembly.
AB  - The 26S proteasome is a highly conserved protein degradation machine that
      consists of the 20S proteasome and 19S regulatory particles, which include 14 and
      19 different polypeptides, respectively. How the proteasome components are
      assembled is a fundamental question towards understanding the process of protein
      degradation and its functions in diverse biological processes. Several proteasome
      dedicated chaperones are involved in the efficient and correct assembly of the
      20S proteasome. These chaperones help the initiation and progression of the
      assembly process by transiently associating with proteasome precursors. By
      contrast, little is known about the assembly of the 19S regulatory particles, but
      several hints have emerged.

PMID- 19165214
TI  - MicroRNAs: key regulators of stem cells.
AB  - The hallmark of a stem cell is its ability to self-renew and to produce numerous
      differentiated cells. This unique property is controlled by dynamic interplays
      between extrinsic signalling, epigenetic, transcriptional and post
      transcriptional regulations. Recent research indicates that microRNAs (miRNAs)
      have an important role in regulating stem cell self-renewal and differentiation
      by repressing the translation of selected mRNAs in stem cells and differentiating
      daughter cells. Such a role has been shown in embryonic stem cells, germline stem
      cells and various somatic tissue stem cells. These findings reveal a new
      dimension of gene regulation in controlling stem cell fate and behaviour.

PMID- 19165216
TI  - Adiposcience and adipotoxicity.

PMID- 19165217
TI  - Does attainment of target levels of growth hormone and insulin-like growth factor
      I improve acromegaly prognosis?

PMID- 19165218
TI  - Should 123I-MIBG scintigraphy be part of the workup for pheochromocytomas?

PMID- 19165215
TI  - Biogenesis of small RNAs in animals.
AB  - Small RNAs of 20-30 nucleotides can target both chromatin and transcripts, and
      thereby keep both the genome and the transcriptome under extensive surveillance.
      Recent progress in high-throughput sequencing has uncovered an astounding
      landscape of small RNAs in eukaryotic cells. Various small RNAs of distinctive
      characteristics have been found and can be classified into three classes based on
      their biogenesis mechanism and the type of Argonaute protein that they are
      associated with: microRNAs (miRNAs), endogenous small interfering RNAs (endo
      siRNAs or esiRNAs) and Piwi-interacting RNAs (piRNAs). This Review summarizes our
      current knowledge of how these intriguing molecules are generated in animal
      cells.

PMID- 19165219
TI  - Is bone loss after gastric bypass surgery associated with the extent of weight
      loss?

PMID- 19165220
TI  - Is the treatment of subclinical hypothyroidism beneficial?

PMID- 19165221
TI  - Radiation-induced hypopituitarism after cancer therapy: who, how and when to
      test.
AB  - Subtle to frank abnormalities in hypothalamic-pituitary axis function are
      frequently seen in cancer survivors who have received prophylactic or therapeutic
      cranial irradiation. The growth hormone (GH) axis is the most vulnerable to
      radiation damage, and isolated GH deficiency can occur after doses as low as 18
      Gy. Furthermore, the frequency of GH deficiency can reach 50-100% within 3-5
      years of cranial irradiation with doses of 30-50 Gy. TSH and adrenocorticotropic
      hormone deficiency occur in 3-6% of patients after conventional irradiation (30
      50 Gy). Abnormalities in gonadotropin secretion are dose-dependent: gonadotropin
      deficiency is seen only after doses of 30 Gy or more, whereas lower doses usually
      lead to precocious puberty. Hyperprolactinemia predominantly occurs in young
      women after intensive irradiation and is usually subclinical. The frequencies of
      gonadotropin, adrenocorticotropic hormone and TSH deficiencies substantially
      increase with intensive irradiation (greater than 60 Gy) and after conventional
      irradiation for pituitary tumors, with a cumulative incidence of 30-60% after 10
      years. The irreversible and progressive nature of radiation-induced anterior
      pituitary hormone deficiencies and their adverse effect on body image, growth,
      sexual function, skeletal health and quality of life makes it essential that
      cancer survivors are tested regularly to ensure appropriate diagnosis and timely
      hormone replacement therapy.

PMID- 19165222
TI  - Advances in the diagnosis and management of hyperinsulinemic hypoglycemia.
AB  - Hyperinsulinemic hypoglycemia (HH) is a consequence of unregulated insulin
      secretion by pancreatic beta-cells and is a major cause of hypoglycemic brain
      injury and mental retardation. Congenital HH is caused by mutations in genes
      involved in regulation of insulin secretion, seven of which have been identified
      (ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1 and HNF4A). Severe forms of congenital
      HH are caused by mutations in ABCC8 and KCNJ11, which encode the two components
      of the pancreatic beta-cell ATP-sensitive potassium channel. Mutations in HNF4A,
      GLUD1, CGK, and HADH lead to transient or persistent HH, whereas mutations in
      SLC16A1 cause exercise-induced HH. Rapid genetic analysis combined with an
      understanding of the histological features (focal or diffuse disease) of
      congenital HH and the introduction of (18)F-L-3,4-dihydroxyphenylalanine PET-CT
      to guide laparoscopic surgery have totally transformed the clinical approach to
      this complex disease. Adult-onset HH is mostly caused by an insulinoma; however,
      it has also been reported to present as postprandial HH in patients with
      noninsulinoma pancreatogenous hypoglycemia syndrome, in those who have undergone
      gastric-bypass surgery for morbid obesity, and in those with mutations in the
      insulin-receptor gene.

PMID- 19165223
TI  - Testosterone and ill-health in aging men.
AB  - As men age, testosterone levels decline, and decreased testosterone levels are
      associated with increased risks of osteoporosis, metabolic syndrome, type 2
      diabetes mellitus and mortality. Nevertheless, it is still uncertain whether
      reduced testosterone level is a cause of ill-health or a marker of pre-existing
      disease, as systemic illness lowers testosterone levels. Most circulating
      testosterone is bound to sex-hormone-binding globulin (SHBG) and albumin, whereas
      a small proportion circulates as free testosterone. Decreased SHBG level is
      associated with increased risks for insulin resistance and metabolic syndrome,
      although it would also be expected to be associated with increased free
      testosterone level. During male aging, total and free testosterone levels fall
      while SHBG level rises. Thus, associations between decreasing androgens and
      negative health outcomes might differ across men of various ages. Trials of
      testosterone therapy report benefits for body composition and BMD, but there are
      limited data on the effect of testosterone supplementation on cardiovascular
      risk. Whereas men who have androgen deficiency should be considered for
      testosterone therapy, the role of testosterone supplementation in older men who
      are not clearly hypogonadal requires further clarification. Further studies are
      also needed to establish whether the age-related decline in circulating
      testosterone level in men can be modified or prevented.

PMID- 19165225
TI  - p53 polymorphisms: cancer implications.
AB  - The normal functioning of p53 is a potent barrier to cancer. Tumour-associated
      mutations in TP53, typically single nucleotide substitutions in the coding
      sequence, are a hallmark of most human cancers and cause dramatic defects in p53
      function. By contrast, only a small fraction, if any, of the >200 naturally
      occurring sequence variations (single nucleotide polymorphisms, SNPs) of TP53 in
      human populations are expected to cause measurable perturbation of p53 function.
      Polymorphisms in the TP53 locus that might have cancer-related phenotypical
      manifestations are the subject of this Review. Polymorphic variants of other
      genes in the p53 pathway, such as MDM2, which might have biological consequences
      either individually or in combination with p53 variants are also discussed.

PMID- 19165227
TI  - RUNX proteins in transcription factor networks that regulate T-cell lineage
      choice.
AB  - Recent research has uncovered complex transcription factor networks that control
      the processes of T-cell development and differentiation. RUNX (runt-related
      transcription factor) proteins are among the many factors that have crucial roles
      in these networks. In this Review, we examine the mechanisms by which RUNX
      complexes act together with other transcription factors, such as Th-POK (T-helper
      inducing POZ/Kruppel-like factor) and GATA-binding protein 3 (GATA3) in
      determining the CD4/CD8 lineage choice of developing thymocytes. In addition, we
      discuss evidence indicating that RUNX complexes are also involved in the
      differentiation of effector T-cell subsets and that the molecular mechanisms by
      which RUNX proteins regulate T-cell fate decisions are conserved between the
      thymus and periphery.

PMID- 19165226
TI  - A tense situation: forcing tumour progression.
AB  - Cells within tissues are continuously exposed to physical forces including
      hydrostatic pressure, shear stress, and compression and tension forces. Cells
      dynamically adapt to force by modifying their behaviour and remodelling their
      microenvironment. They also sense these forces through mechanoreceptors and
      respond by exerting reciprocal actomyosin- and cytoskeletal-dependent cell
      generated force by a process termed 'mechanoreciprocity'. Loss of
      mechanoreciprocity has been shown to promote the progression of disease,
      including cancer. Moreover, the mechanical properties of a tissue contribute to
      disease progression, compromise treatment and might also alter cancer risk. Thus,
      the changing force that cells experience needs to be considered when trying to
      understand the complex nature of tumorigenesis.

PMID- 19165229
TI  - TOM-independent complex formation of Bax and Bak in mammalian mitochondria during
      TNFalpha-induced apoptosis.
AB  - The Bcl-2 family proteins Bax and Bak are activated in response to many apoptotic
      stimuli. As a consequence of activation, Bax and Bak oligomerize and permeabilize
      the outer mitochondrial membrane to permit the release of apoptosis-inducing
      factors. It still remains unclear whether these proteins require components of
      the mitochondrial protein import machinery for their function at the
      mitochondria. Here, we addressed this question by using inducible RNA
      interference for the study of protein import in mammalian mitochondria. After
      induction of apoptosis, we could not detect any impact of the absence of Tom22,
      Tom70, Tom40, Sam50 or metaxins on the translocation of Bax and formation of Bax
      and Bak complexes in mitochondria. In in vitro import studies, loss of these
      import and assembly proteins had no or only slight effect on the formation of
      complexes by radiolabeled Bax and Bak. We conclude that the import and assembly
      machineries of mammalian mitochondria have no impact on the translocation and
      complex assembly of Bax and Bak upon apoptosis induction.

PMID- 19165230
TI  - Role of HCN4 channel in preventing ventricular arrhythmia.
AB  - Bradycardia is a trigger of ventricular arrhythmias in patients with arrhythmia
      including Brugada syndrome and long QT syndrome. The HCN4 channel controls the
      heart rate, and its mutations predispose to inherited sick sinus syndrome and
      long QT syndrome associated with bradycardia. We found a 4 base-insertion at the
      splice donor site of the HCN4 gene in a patient with idiopathic ventricular
      tachycardia, which was supposed to generate a truncated channel. To investigate
      the role of the HCN4 channel in ventricular arrhythmia, we introduced a
      ventricular action potential of I(f) channel produced by HCN4 in a computer
      simulation model and found that the I(f) channel generated a leaky outward
      current during the plateau phase of ventricular action potential. Currents
      through the I(f) channel were suggested to contribute to the shortening of the
      action potential duration and the prevention of early after-depolarization in
      bradycardia. These observations suggested that the HCN4 channel played a
      preventive role in triggering bradycardia-induced ventricular arrhythmias.

PMID- 19165228
TI  - The different faces of Notch in T-helper-cell differentiation.
AB  - Interleukin-12 (IL-12) and IL-4 induce T helper 1 (T(H)1)- and T(H)2-cell
      differentiation, respectively, in vitro. However, not all T(H)1-cell responses
      require IL-12 in vivo, and T(H)2-cell responses are remarkably independent of IL
      4-receptor signalling, suggesting that other polarizing signals must exist.
      Accumulating evidence indicates that Notch is a candidate receptor that might
      mediate these signals. However, contrasting roles for Notch have been proposed:
      some evidence shows that Notch promotes T(H)1-cell differentiation, whereas other
      evidence supports a prominent role for Notch in T(H)2-cell differentiation. In
      this Review, we discuss recent findings that help to reconcile this discrepancy
      and highlight the accumulating evidence for the role of Notch in T-cell-mediated
      diseases.

PMID- 19165231
TI  - HLA-DPB1 and NFKBIL1 may confer the susceptibility to chronic thromboembolic
      pulmonary hypertension in the absence of deep vein thrombosis.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by
      pulmonary hypertension caused by thromboembolism of the pulmonary artery.
      Etiology of CTEPH may be heterogeneous and is largely unknown, but genetic
      factors are considered to be involved in the etiology. It has been reported that
      deep vein thrombosis (DVT) and/or coagulation factor variants are predisposing
      factors to CTEPH. However, more than half of the CTEPH patients, especially the
      Japanese, do not have prior DVT or coagulation abnormality, suggesting that there
      should be other risk factors for CTEPH. Moreover, there are several reports on
      the association between CTEPH and human leukocyte antigen (HLA). To further
      clarify the HLA-linked gene(s) controlling the susceptibility to CTEPH, 160
      patients (99 without DVT and 61 with DVT) and 380 healthy controls were analyzed
      for polymorphisms in 15 microsatellite markers and 5 genes in the HLA region. We
      found a strong association of HLA markers with the DVT-negative CTEPH,
      DPB1(*)0202 (odds ratio (OR)=5.07, 95% confidence interval (CI)=2.52-10.19,
      P=0.00000075, corrected P-value (Pc)=0.00014), IKBL-p(*)03 (OR=2.33, 95% CI=1.49
      3.66, P=0.00017, Pc=0.033) and B(*)5201 (OR=2.47, 95% CI=1.56-3.90, P=0.000086,
      Pc=0.016), whereas no significant association was observed for the DVT-positive
      CTEPH. The comparison of clinical characteristics of patients stratified by the
      presence of susceptibility genes implied that the DPB1 gene controlled the
      severity of the vascular lesion, whereas the IKBL gene (NFKBIL1) was associated
      with a relatively mild phenotype.

PMID- 19165232
TI  - Genome-wide association study of panic disorder in the Japanese population.
AB  - Panic disorder (PD) is an anxiety disorder characterized by panic attacks and
      anticipatory anxiety. Although a number of association studies have been
      conducted, no gene has been identified as a susceptibility locus. In this study,
      we conducted a genome-wide association study of PD in 200 Japanese patients and
      the same number of controls, using the GeneChip Human Mapping 500 K Array Set.
      Genotypes were determined using the Bayesian Robust Linear Model with Mahalanobis
      (BRLMM) genotype calling algorithm. The genotype data were data-cleaned using
      criteria for SNP call rate (>or=95%), Hardy-Weinberg equilibrium (P>or=0.1%) and
      minor allele frequency (>or=5%). The significance level of the allele P-value was
      set at 1.0 x 10(-6), to make false discovery rate (FDR) <0.05. As a result, seven
      SNPs were significantly associated with PD, which were located in or adjacent to
      genes including PKP1, PLEKHG1, TMEM16B, CALCOCO1, SDK2 and CLU (or APO-J).
      Studies with other samples are required to confirm the results.

PMID- 19165234
TI  - Multitarget therapy of malignant cancers by the head-to-tail tandem array
      multiple shRNAs expression system.
AB  - Coexpression of multiple shRNAs can simultaneously inhibit multiple genes or
      target multiple sites on a single gene. These approaches can be used for
      dissecting complex signaling pathways and even be applied to targeting multiple
      genes in cancer therapy. Here we established a simple and efficient multiple
      shRNAs expression system based on pSUPER, the most popular expression vector in
      mammalian cells. A series of head-to-tail tandem array multiple shRNAs expression
      vectors were constructed containing different combinations of six shRNA
      expression cassettes targeting genes involved in cell proliferation and survival
      pathways: Bcl-2, Survivin, Akt1, Erk2, CyclinE and NFkappaB. In HeLa and HEK293
      cells, the multiple shRNAs expression constructs could efficiently and
      simultaneously induce inhibition of all six genes. We further evaluated the
      inhibition effects of the multiple shRNAs expression vectors on the human
      prostate cancer cell line PC3, which contains different cell variants with
      distinct oncogenic signaling alterations. The results revealed that the multiple
      shRNAs expression system could inhibit all six genes and was much more efficient
      in inducing apoptosis in the PC3 cells. Our results suggest that the multitarget
      shRNAs expression system could be an effective strategy in cancer therapy and be
      applied to any other DNA vector-based shRNA expression system.

PMID- 19165235
TI  - P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling
      pathway by cetuximab.
AB  - Cetuximab (Erbitux) is an anti-epidermal growth factor receptor (EGFR) monoclonal
      antibody whose activity is related to the inhibition of EGFR downstream signaling
      pathways. P53 and phosphatase and tensin homologue deleted on chromosome 10
      (PTEN) have been reported to control the functionality of PI3K/AKT signaling. In
      this study we evaluated whether reintroducing P53 using non-viral gene transfer
      enhances PTEN-mediated inhibition of PI3K/AKT signaling by cetuximab in PC3
      prostate adenocarcinoma cell line bearing p53 and pten mutations. Signaling
      phosphoproteins expression was analyzed using Bio-Plex phosphoprotein array and
      western blot. Apoptosis induction was evaluated from BAX expression, caspase-3
      activation and DNA fragmentation analyses. The results presented show that p53
      and pten gene transfer additionally mediated cell growth inhibition and apoptosis
      induction by restoral of signaling functionality, which enabled the control of
      PI3K/AKT and MAPKinase signaling pathways by cetuximab in PC3 cells. These
      results highlight the interest of the analysis of signaling phosphoproteins
      expression as molecular predictive markers for response to cetuximab and show
      that p53 and pten mutations could be key determinants of cell response to
      cetuximab through the functional impact of these mutations on cell signaling.

PMID- 19165236
TI  - Allele-specific cancer cell killing in vitro and in vivo targeting a single
      nucleotide polymorphism in POLR2A.
AB  - Cancer is one of the diseases for which RNA interference is a potential
      therapeutic approach. Genes involved in the promotion or maintenance of tumor
      growth are obvious targets for RNAi. RNAi is also considered an attractive
      additional approach to conventional chemotherapy for cancer treatment. Moreover,
      siRNAs have shown a high specificity for their molecular target mRNAs as they can
      selectively inhibit cancer-promoting genes that differ by a point mutation. Loss
      of heterozygosity (LOH) reduces genes to hemizygosity in cancer cells and
      presents an absolute difference between normal and cancer cells. The regions of
      LOH are usually much larger than the tumor suppressor gene, which is lost, and
      has been shown to contain genes that are essential for cell survival. Single
      nucleotide polymorphisms (SNPs) are the most common type of genetic variation in
      man. SNPs in essential genes that are frequently affected by LOH can be used as a
      target for a therapy against cancer cells with LOH. We have designed siRNAs
      against the gene of the large subunit of RNA polymerase II (POLR2A), a gene
      located in close proximity to the tumor suppressor gene p53, which frequently
      shows LOH in cancer cells. It is shown in vitro that siRNA can selectively
      inhibit POLR2A expression dependent on its genotype. Furthermore, cancer cell
      proliferation and tumor growth inhibition in nude mice was genotype dependent. We
      conclude that siRNA can be used for genotype-specific inhibition of tumor growth
      targeting an SNP in POLR2A in vivo.

PMID- 19165233
TI  - Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and
      inflammatory disease.
AB  - Cells in the human body need oxygen to function and survive, and severe
      deprivation of oxygen, as occurs in ischaemic heart disease and stroke, is a
      major cause of mortality. Nevertheless, other organisms, such as the fossorial
      mole rat or diving seals, have acquired the ability to survive in conditions of
      limited oxygen supply. Hypoxia tolerance also allows the heart to survive chronic
      oxygen shortage, and ischaemic preconditioning protects tissues against lethal
      hypoxia. The recent discovery of a new family of oxygen sensors--including prolyl
      hydroxylase domain-containing proteins 1-3 (PHD1-3)--has yielded exciting novel
      insights into how cells sense oxygen and keep oxygen supply and consumption in
      balance. Advances in understanding of the role of these oxygen sensors in hypoxia
      tolerance, ischaemic preconditioning and inflammation are creating new
      opportunities for pharmacological interventions for ischaemic and inflammatory
      diseases.

PMID- 19165237
TI  - Clinicians' knowledge and practice of data protection legislation and information
      management.
AB  - AIMS: The aim of this study was to review current legislation and guidance on
      information governance and to audit clinicians' management of confidential
      patient information and knowledge of published guidelines in a teaching hospital.
      MATERIALS AND METHODS: A questionnaire was developed based on published
      Department of Health, General Dental Council and National Health Service
      guidance. This was then piloted and distributed to clinicians to complete.
      RESULTS: A review of the current guidance revealed many confusing and unclear
      areas. However, clinicians' knowledge of information governance was generally
      good, with an overall correct response rate of 73%. CONCLUSIONS: All clinicians
      have an ethical and legal obligation to protect confidential patient data and to
      be aware of their responsibilities. Local guidelines need to be clarified to help
      clinicians to manage patient data effectively.

PMID- 19165238
TI  - Tidal wave with a deaf ear.

PMID- 19165239
TI  - Baboon syndrome.

PMID- 19165240
TI  - Paediatric sedation.

PMID- 19165241
TI  - U-turn.

PMID- 19165242
TI  - Lessons from Latin.

PMID- 19165243
TI  - Occlusal conflict.

PMID- 19165244
TI  - Turtle recall.

PMID- 19165245
TI  - Rubber revolution.

PMID- 19165246
TI  - Tactful history.

PMID- 19165247
TI  - Couplands' chisels.

PMID- 19165248
TI  - Apprenticeship Awards seek dental involvement.

PMID- 19165254
TI  - UK top for high quality research.

PMID- 19165257
TI  - Study looks at laughing gas and dental patients.

PMID- 19165259
TI  - A view of European challenges in dental education.
AB  - Since the Bologna declaration in 1999 there have been significant developments in
      undergraduate dental education. The GDC and the UK dental education community
      need to rise to these challenges.

PMID- 19165261
TI  - Bacterial meningitis after tooth extraction.
AB  - Wound infections after tooth extraction may occur in up to 5%. A systemic
      infection is a rare but threatening complication often caused by an underlying
      immune deficiency (immunosuppression, diabetes, HIV) which requires prompt
      adequate care. This case report describes bacterial meningitis as a possible
      systemic complication two days after the extraction of a molar in a patient with
      previously undiagnosed latent diabetes mellitus.

PMID- 19165260
TI  - Massive sublingual haematoma following osseo-integrated implant placement in the
      anterior mandible.
AB  - The floor of the mouth is a very vascular area. Should perforation of the lingual
      cortex of the mandible occur during the placement of an osseo-integrated implant,
      significant haemorrhage may result. We present the case of a patient who attended
      our unit with acute airway obstruction. Although life threatening haematoma
      following the placement of osseo-integrated implants in the interforaminal area
      of the mandible is known to occur, there continue to be sporadic reports in the
      literature. This shows that some practitioners are unaware of the risks involved
      and place implants of the wrong size and orientation.

PMID- 19165262
TI  - Cervicofacial infection of dental origin presenting to maxillofacial surgery
      units in the United Kingdom: a national audit.
AB  - INTRODUCTION: Local studies have shown an increase in cervicofacial infections of
      dental origin presenting to oral and maxillofacial surgery units in the UK. A
      lack of access to National Health Service (NHS) primary care dental services has
      been implicated as a root cause. STUDY DESIGN: Cross-sectional national
      audit.Method Oral and maxillofacial surgery units in the UK were asked to report
      details of severe cervicofacial infection of dental origin presenting in October
      and November 2006. Data were collected regarding: patient demographics, referral
      source, management in primary care, management by maxillofacial surgery, and
      outcome. RESULTS: Two hundred and sixty-six episodes of cervicofacial infection
      of dental origin were reported during the audit period. At the time of
      presentation, 56.4% of patients were registered with a general dental
      practitioner (GDP). One hundred and forty (52.6%) patients sought treatment from
      primary care dental services for their episode of cervicofacial infection and
      only 20 patients were unsuccessful in obtaining treatment. Forty-seven percent of
      patients did not seek treatment from primary care dental services. Fifty percent
      of patients were referred by accident and emergency. Sixty-six percent of
      patients were prescribed oral antibiotics without operative intervention by
      primary dental care services. Eighty-one percent of patients required hospital
      admission and 46% of patients required a surgical procedure under general
      anaesthesia. Eighty-nine percent of patients made a full recovery and 3%
      recovered with complications. There were no deaths reported during the audit
      period. DISCUSSION: This audit provides a benchmark from which future comparisons
      can be made and by design cannot prove an increase in the presentation of
      cervicofacial infection of dental origin. Lack of access to NHS primary care
      dental services may be less significant than originally thought. A significant
      proportion of patients preferentially present to primary care medical services
      rather than dental services. Two thirds of patients treated by primary care
      dental services received oral antibiotics only which represents an inadequate
      level of treatment for odontogenic infection.

PMID- 19165263
TI  - A clinical guide to endodontics - update part 1.
AB  - This is the first of two opinion papers that aim to provide a review of changes
      and developments that have occurred within the field of root canal treatment for
      both permanent and primary teeth since the publication in 2004 of the BDJ's
      textbook A clinical guide to endodontics. This, the first part, considers the
      changes in thinking and practice that have occurred with regard to the treatment
      of permanent teeth, in particular the continued significant move toward the use
      of nickel titanium rotary instruments. Knowledge of the changes discussed in this
      paper is essential both for the best possible prognosis of treatment, and when
      obtaining informed or valid consent to treatment.

PMID- 19165270
TI  - Dental extractions and bisphosphonates: the assessment, consent and management, a
      proposed algorithm.
AB  - Bisphosphonate-associated osteonecrosis of the jaws (BONJ) is recognised as a
      significant complication related to the use of bisphosphonates and currently is
      gaining importance due to the increasingly widespread use of these medications.
      Patients are placed into low or high risk groups of developing BONJ depending on
      the systemic condition for which they have received bisphosphonates. Numerically,
      the largest group worldwide is patients receiving bisphosphonates for
      osteoporosis and these generally fall into the low risk group for BONJ. The high
      risk group, while numerically smaller, is composed of those patients receiving
      bisphosphonates in the management of malignancy affecting the skeleton, either
      primary or secondary (metastatic disease). A number of additional systemic and
      local risk factors are proposed, which have the effect of increasing the risk of
      BONJ following an extraction. These risk factors may have the effect of moving a
      low risk categorised patient into a medium, or perhaps more realistically an
      unknown risk category. An example of a systemic risk factor is the concurrent use
      of corticosteroids and a local risk factor is mandibular molar extraction. The
      purpose of this paper is to define and validate an algorithm to guide clinicians
      in the area of patient information, consent and management for patients currently
      taking or having previously taken bisphosphonates who require dental extractions.

PMID- 19165286
TI  - Dental mission for children--Vietnam.
AB  - This article by Noel Perkins and Lan Jones describes the ongoing work of the
      charity Dental Mission for Children, which provides dental care and dental health
      education in socioeconomically deprived areas of Vietnam.

PMID- 19165287
TI  - [Cure of type 1 diabetes mellitus. Is it a reachable goal?].

PMID- 19165288
TI  - [New therapeutic strategies for type 1 diabetes mellitus].
AB  - The main determinant of the risk of complications from type 1 diabetes mellitus
      is the total lifetime blood glucose levels. To impact on the health and quality
      of life of individuals with diabetes, safe and effective methods of achieving and
      maintaining normoglycemia are needed. Unfortunately, intensive insulin therapy
      does not achieve normal levels of blood glucose, is difficult to implement for
      many patients, and limited by the accompanying increased frequency of severe
      hypoglycemia. Hence, the only way at present to restore permanently normoglycemia
      without hypoglycemia is to provide the patient with additional beta-cells. This
      can be achieved by transplanting an intact pancreas, or by transplanting islets.
      The shortage of functional beta-cells from available donors is one of the major
      limiting factors for the treatment of diabetes by islet transplantation.
      Therefore, methods to preserve or even promote regeneration of the beta-cell mass
      are dearly needed. Significant progress has been made over the last decade in
      stem cell biology. However, the quest for identification of stem cells has been
      hampered by the lack of appropriate research tools including assays that allow
      assess their differentiation potential in vitro and in vivo. Therefore, new
      techniques are necessary in order to develop new therapeutic strategies based on
      stem cells for the treatment of diabetes mellitus type 1.

PMID- 19165289
TI  - [Rachitic deformities of lower members in congolese children].
AB  - BACKGROUND: To analyse risk factors in rachitic Congolese children with serious
      deformities in their lower members and to describe the lesions. METHODS: The
      authors analysed the parameters obtained in a survey of two groups of children: a
      group of 194 rachitic children with severe deformities of their members and
      another control group of 107 healthy children of similar ages. The types of
      deformity and the degrees of rachitism were described. RESULTS: The most frequent
      deformity was genu varum (58.2%), followed by windsept (23.7%) and genu valgum
      (13.9%). Genu varum predominated in girls of between 2-4 years (p=0.0025). We
      found florid rickets in 19.1% of the cases, moderate in 15.5%, minimal in 14.2%
      and osseous deformities alone without active rachitism in 41.2%. Of the
      parameters analysed, the most important risk factor was being a twin (OR=25.43 ;
      95% CI=3.76-1098.27), followed by lack of sunlight (OR=18.39, 95% CI=6.69-61.55)
      and having a rachitic sibling. Maternal feeding was a protective factor (OR=0.94,
      95% CI=0.90-0.98). Premature birth and low weight at birth had no influence.
      Walking age was 15.4 months in the rachitic cases and 12.4 months in the control
      group (p<0,01). CONCLUSION: Severe deformities of lower members as a sequel to
      rickets are frequent; they are associated with being a twin, lack of sunlight and
      precocious weaning.

PMID- 19165290
TI  - [Agreement between ophthalmologist and nurse in the first postoperative
      exploration following cataract extraction].
AB  - INTRODUCTION: Nursing activity in the cataract extraction process extends from
      carrying out biometry in the preoperative stage and collaboration in surgery, to
      providing the initial care in the postoperative stage and keeping the patient and
      family informed throughout the whole process. This article analyses agreement
      between ophthalmologists and nurses in the findings of the first post-surgical
      exploration of patients of cataract extraction using facoemulsification and
      without complications in surgery. METHODS: The study was carried out between May
      and June of 2005 on 129 patients who had been operated on for cataracts, 78 women
      and 51 men with an average age of 73.1 years. The variables to be evaluated in
      the first post-surgical exploration were defined, and a study was made of the
      agreement between ophthalmologists and nurses in identification of the most
      frequent complications in cataract surgery. RESULTS: Agreement was 100% in the
      cases of intraocular pressure >22 mm Hg, pupil irregularity, inflammatory
      reaction of the anterior chamber and iris prolapse; it was 65.9% on the presence
      of Seidel; and 60.5% on severe corneal edema. CONCLUSIONS: The high rate of
      agreement between ophthalmologists and nurses in 4 of the variables might offer
      the possibility of the nurse carrying out this post-surgical exploration.
      However, a moderate rate of agreement in the other variables makes a longer
      training period for nursing personnel necessary in order to obtain higher values.

PMID- 19165291
TI  - [Genetic predisposition to bleeding during oral anticoagulants treatment].
AB  - The degree of anticoagulation obtained during oral anticoagulation therapy with
      vitamin K antagonists (VKA) varies among patients due to individual and
      environmental factors. The rate of anticoagulation influences the hemorrhagic
      risk. Therefore, it is plausible that patients specially sensitive to oral
      anticoagulants are at higher hemorrhagic risk, specially during the first weeks.
      The role of a series of polymorphisms of the enzymes involved in the metabolism
      of VKA or in the vitamin K cycle are reviewed. Three polymorphisms, two in the
      cytochrome P450 2C9 and one in the VKORC1 enzyme, are responsible for a high
      portion of the variability observed in the sensitivity to AVK. Although the
      available literature suggests that these genetic variants could increase the risk
      of severe hemorrhage, larger, well designed studies are needed to confirm this
      notion.

PMID- 19165292
TI  - [Influence of dietary intake on plasma biomarkers of oxidative stress in humans].
AB  - Oxidative stress is related to an imbalance between the production of reactive
      species and the antioxidant defenses. In essence, oxidative stress has been
      defined as a disturbance in the pro-oxidant/antioxidant balance, leading to
      potential damage. It has been suggested that oxidative stress is involved in the
      etiology of several chronic diseases including cardiovascular disease, diabetes,
      cancer and neurodegenerative processes. The antioxidant defenses include
      nonenzymatic (especially dietary antioxidants) and antioxidant enzymes. Vitamins,
      minerals and phytochemicals (polyphenols and carotenoids) are among the major
      dietary antioxidants. The assessment of oxidative stress status though specific
      biomarkers has acquired great importance. The major biomarkers include the
      products of the attack of free radicals and reactive species to various
      substrates: lipids, proteins and nucleic acids. Measurement of antioxidant
      capacity may also involve the assessment of specific oxidative stress biomarkers.
      Most of the studies that have examined the association between diet and oxidative
      stress consider the effects of antioxidant supplements (vitamins and minerals),
      drinks and foods with bioactive compounds or dietary patterns on oxidative stress
      biomarkers. Some of these studies have demonstrated beneficial results on
      oxidative stress markers. However, the role of diet on oxidative stress
      biomarkers remains unclear and represents a potentially fruitful area for further
      research in the health area.

PMID- 19165293
TI  - [Foetal/neonatal alloimmune thrombocytopenia. A review and case report].
AB  - Foetal/neonatal alloimmune thrombocytopenia is the most common cause of severe
      thrombocytopenia in the newborn. It is an acute disorder which implies that
      foetal platelets are destroyed during the pregnancy due to a maternal alloimmune
      IgG antibody. More than 80% of Caucasians are HPA-1a specific. Intracranial
      haemorrhage, which occurs in 30% of cases, is the most serious complication, with
      a 10% mortality rate or a 20% rate of irreversible neurological sequels. The high
      risk of a recurrence of serious bleeding in future pregnancies led us to consider
      prophylaxis or prenatal treatment. An early diagnosis of this process allows an
      effective therapy to be carried out based on the infusion of compatible phenotype
      HPA platelets or endovenous immunoglobulins. We present the case of a 27 year old
      pregnant woman, who in the 35th week of a second pregnancy was diagnosed using
      echography with a bilateral foetal hydrocephaly. After caesarean delivery in the
      36th week, the newborn presented haematomas in the left shoulder and gluteus,
      macrocephalia with tension of the fontanellas and hemorrhagic cerebrospinal fluid
      after insertion of an external ventricular derivation catheter. The haemogram
      revealed a severe trombocytopenia (9 x 109/L). In the light of clinical suspicion
      of foetal/neonatal alloimmune thrombocytopenia, infusion was made of platelets
      from a non-phenotyped donor for the HPA-1a system, and an endovenous
      immunoglobulin treatment was followed, with a recovery of platelet counts, but
      with neurological sequels that are probably irreversible. The immunohaematologal
      study confirmed the negative HPA-1a maternal phenotype, the neonatal HPA-1a
      positive phenotype and the presence of anti-HPA-1a alloantibodies in the maternal
      serum. Nowadays, the prophylaxis and treatment continue to be a controversial
      issue that is open to discussion, as is the possibility of implementing antenatal
      screening.

PMID- 19165294
TI  - [Outbreak of dermatitis caused by pine processionary caterpillar (Thaumetopoea
      pityocampa) in schoolchildren].
AB  - BACKGROUND: To describe a dermatitis outbreak caused by exposure to pine
      processionary caterpillar (Thaumetopoea pityocampa ) that took place on March
      15th, 2006, in schoolchildren during their stay at a rural farm holiday centre in
      Villahermosa del Rio (Castellon). METHODS: A cross sectional epidemiological
      study was carried out on seventy schoolchildren, average age 10 years, and 3
      teachers from Castellon. A specific questionnaire was used to be filled in by the
      schoolchildren. RESULTS: Six cases of dermatitis (attack rate 8.6%: 6/70) took
      place after children had swum in the heated farm pool and dried themselves with
      towels that had been left outside the heated pool enclosure, where they had come
      into contact with Thaumetopoea pityocampa. The cases needed medical attention,
      with prescription of antihistamine drugs, corticosteroids, and cold showers. The
      risk of dermatitis from contact with Thaumetopoea pityocampa was very high (Odds
      Ratio=157.2 Confidence Interval 95% 18.4-inf). Thaumetopoea pityocampa were
      collected near the swimming pool and Thaumetopoea pityocampa nests were observed
      on nearby pines. CONCLUSIONS: The presence of Thaumetopoea pityocampa near rural
      centres can cause outbreaks. Health education for schoolchildren and the removal
      of Thaumetopoea pityocampa nests near these centres are required.

PMID- 19165295
TI  - [Chondroblastoma of the carpal scaphoids].
AB  - A chondroblastoma is a benign tumour of cartilaginous origin which represents
      less than 1% of all primary osseous tumours. It is typically localised in the
      epiphysis of the long bones. Some 10% of chondroblastomas affect the bones of the
      foot and the hand. It is extremely rare for the seat of this lesion to be in the
      carpal bones. We present a case of chondroblastoma of the carpal scaphoids that
      was treated through curretage of the lesion and filling with autologous osseous
      graft from the iliac crest.

PMID- 19165296
TI  - Analysis of growth of interventional techniques in managing chronic pain in the
      Medicare population: a 10-year evaluation from 1997 to 2006.
AB  - BACKGROUND: Recent reports of the United States Government Accountability Office
      (GAO), the Medicare Payment Advisory Commission (MedPAC), and the Office of
      Inspector General (OIG) expressed significant concern with overall fiscal
      sustainability of Medicare and exponential increase in costs for interventional
      pain management techniques. Interventional pain management (IPM) is an evolving
      specialty amenable to multiple influences. Evaluation and isolation of
      appropriate factors for increasing growth patterns have not been performed. STUDY
      DESIGN: Analysis of the growth of interventional techniques in managing chronic
      pain in Medicare beneficiaries from 1997 to 2006. OBJECTIVE: To evaluate the use
      of all interventional techniques. METHODS: The standard 5% national sample of the
      CMS carrier claim record data for 1997, 2002, and 2006 was utilized. This data
      set provides information on Medicare enrollees in the fee-for-service Medicare
      program. Current procedural technology (CPT) codes for 1997, 2002, and 2006 were
      used to identify the number of procedures performed each year, and trends in
      expenditures. RESULTS: Interventional techniques increased significantly in
      Medicare beneficiaries from 1997 to 2006. Overall, there was an increase of 137%
      in patients utilizing IPM services with an increase of 197% in IPM services, per
      100,000 Medicare beneficiaries. The majority of the increases were attributed to
      exponential growth in the performance of facet joint interventions. There was a
      13.9-fold difference in the increase between the state with the lowest rate and
      the state with the highest rate in utilization patterns of interventional
      techniques (California 37% vs. Connecticut 514%), with an 11.6-fold difference
      between Florida and California (431% vs. 37% increase). In 2006, Florida showed a
      12.7-fold difference compared to Hawaii with the lowest utilization rate.
      Hospital outpatient department (HOPD) expenses constituted the highest increase
      with fewer patients treated either in an ambulatory surgery center (ASC) or in
      office setting. Overall HOPD payments constituted 5% of total 2006 Medicare
      payments, in contrast to 57% of total IPM payments, an 11.4-fold difference.
      LIMITATIONS: The limitations of this study include a lack of inclusion of
      Medicare participants in Medicare Advantage plans and potential documentation,
      coding, and billing errors. CONCLUSION: This study shows an overall increase of
      IPM services of 197% compared to an increase of 137% in patients utilizing IPM
      services from 1997 to 2006.

PMID- 19165297
TI  - Evidence-based medicine, systematic reviews, and guidelines in interventional
      pain management: part 3: systematic reviews and meta-analyses of randomized
      trials.
AB  - In recent years, progress and innovations in healthcare are measured by evidence
      based medicine (EBM), systematic reviews, and meta-analyses. A systematic review
      is defined as, "the application of scientific strategies that limit bias by the
      systematic assembly, critical appraisal, and synthesis of all relevant studies on
      a specific topic." In contrast, meta-analysis is the statistical pooling of data
      across studies to generate pooled estimates of effects. Meta-analysis usually is
      the final step in a systematic review. Systematic reviews and meta-analyses are
      labor intensive, requiring expertise in both the subject matter and review
      methodology, and also must follow the rules of EBM which suggest that a formal
      set of rules must complement medical training and common sense for clinicians to
      interpret the results of clinical research effectively. While expertise in the
      subject matter is crucial, expertise in review methods is also particularly
      important. Despite an explosion of systematic reviews and meta-analyses, the
      empiric research on the quality of systematic reviews has shown that not all
      systematic reviews are truly systematic, having highly variable quality,
      deficiencies in methodologic assessment of the quality of the included
      manuscripts, and bias. Even then, systematic review of the literature is
      currently the best, least biased and most rational way to organize, cull,
      evaluate, and integrate the research evidence from among the expanding medical
      and healthcare literature. However, a dangerous discrepancy between the experts
      and the evidence continues to persist in part because multiple instruments are
      available to assess the quality of systematic reviews or meta-analyses. Steps in
      conducting systematic reviews include planning, conducting, reporting, and
      disseminating the results. The Quality of Reporting of Meta-analysis (QUOROM)
      statement provides a checklist and a flow diagram. The checklist describes the
      preferred way to present the abstract, introduction, methods, results, and
      discussion sections of the report of an analysis. This review describes various
      aspects of systematic reviews and meta-analyses of randomized trials with a
      special focus on interventional pain management.

PMID- 19165298
TI  - Evidence-based medicine, systematic reviews, and guidelines in interventional
      pain management: part 4: observational studies.
AB  - Evidence-based medicine (EBM) stresses the examination of evidence from clinical
      research and describes it as a shift in medical paradigms, in contrast to
      intuition, unsystematic clinical experience, and pathophysiologic rationale.
      While the importance of randomized trials has been created by the concept of the
      hierarchy of evidence in guiding therapy, much of the medical research is
      observational. There is competition, contrast, and a feeling of inferiority and
      uselessness for observational studies, created by a lack of understanding of
      medical research. However, observational studies and randomized clinical trials
      (RCTs) can be viewed as the steps of observation and experimentation that form
      the basis of the scientific methodology. Further, rational healthcare practices
      require knowledge about the etiology and pathogenesis, diagnosis, prognosis, and
      treatment of disorders. The reporting of observational research is often not
      detailed and clear enough with insufficient quality and poor reporting, which
      hampers the assessment of strengths and weaknesses of the study and the
      generalizability of the mixed results. Thus, design, implementation, and
      reporting of observational studies is crucial. The biased interpretation of
      results from observational studies, either in favor of or opposed to a treatment,
      and lack of proper understanding of observational studies, leads to a poor
      appraisal of the quality. Similar to the Consolidated Standards of Reporting
      Trials (CONSORT) statement for the reporting of randomized trials, the
      Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE)
      statement was developed with recommendations to improve the quality of reporting
      observational studies. The STROBE statement consists of a checklist of 22 items,
      which relate to the title, abstract, introduction, methods, results, and
      discussion sections of articles. Multiple types of observational studies are
      conducted; however, 3 types have been highlighted in the STROBE document and also
      in the present review, which include cohort studies, case-controlled studies, and
      cross-sectional studies. This comprehensive review provides an introduction and
      rationale, types, design, and reporting of observational studies; outcomes
      assessment and data presentation and analysis; statistical analysis, results, and
      a discussion of observational studies.

PMID- 19165299
TI  - Systematic review of caudal epidural injections in the management of chronic low
      back pain.
AB  - BACKGROUND: Caudal epidural injection of local anesthetics with or without
      steroids is one of the most commonly used interventions in managing chronic low
      back and lower extremity pain. However, there has been a lack of well-designed
      randomized, controlled studies to determine the effectiveness of caudal epidural
      injections in various conditions - disc herniation and radiculitis, post-lumbar
      laminectomy syndrome, spinal stenosis, and chronic low back pain of disc origin
      without disc herniation or radiculitis. STUDY DESIGN: A systematic review of
      caudal epidural injections with or without steroids in managing chronic pain
      secondary to lumbar disc herniation or radiculitis, post lumbar laminectomy
      syndrome, spinal stenosis, and discogenic pain without disc herniation or
      radiculitis. OBJECTIVE: To evaluate the effect of caudal epidural injections with
      or without steroids in managing various types of chronic low back and lower
      extremity pain emanating as a result of disc herniation or radiculitis, post
      lumbar laminectomy syndrome, spinal stenosis, and chronic discogenic pain.
      METHODS: A review of the literature was performed according to the Cochrane
      Musculoskeletal Review Group Criteria as utilized for interventional techniques
      for randomized trials and the Agency for Healthcare Research and Quality (AHRQ)
      criteria for observational studies. The level of evidence was classified as Level
      I, II, or III based on the quality of evidence developed by the U.S. Preventive
      Services Task Force (USPSTF). Data sources included relevant literature of the
      English language identified through searches of PubMed and EMBASE from 1966 to
      November 2008, and manual searches of bibliographies of known primary and review
      articles. OUTCOME MEASURES: The primary outcome measure was pain relief (short
      term relief = up to 6 months and long-term > or = 6 months). Secondary outcome
      measures of improvement in functional status, psychological status, return to
      work, and reduction in opioid intake were utilized. RESULTS: The evidence showed
      Level I for short- and long-term relief in managing chronic low back and lower
      extremity pain secondary to lumbar disc herniation and/or radiculitis and
      discogenic pain without disc herniation or radiculitis. The indicated evidence is
      Level II-1 or II-2 for caudal epidural injections in managing low back pain of
      post-lumbar laminectomy syndrome and spinal stenosis. LIMITATIONS: The
      limitations of this study include the paucity of literature, specifically for
      chronic pain without disc herniation. CONCLUSION: This systematic review shows
      Level I evidence for relief of chronic pain secondary to disc herniation or
      radiculitis and discogenic pain without disc herniation or radiculitis. Further,
      the indicated evidence is Level II-1 or II-2 for caudal epidural injections in
      managing chronic pain of post lumbar laminectomy syndrome and spinal stenosis.

PMID- 19165300
TI  - Systematic review of the effectiveness of cervical epidurals in the management of
      chronic neck pain.
AB  - BACKGROUND: Chronic neck pain is a common problem in the adult population with a
      typical 12-month prevalence of 30% to 50%, and 14% of the patients reporting
      grade II to IV neck pain with high pain intensity and disability that has a
      substantial impact on health care and society. Cervical epidural injections for
      managing chronic neck pain are one of the commonly performed interventions in the
      United States. However, the literature supporting cervical epidural steroids in
      managing chronic pain problems has been scant and no systematic review dedicated
      to the evaluation of cervical interlaminar epidurals has been performed in the
      past. STUDY DESIGN: A systematic review of cervical interlaminar epidural
      injections. OBJECTIVE: To evaluate the effect of cervical interlaminar epidural
      injections in managing various types of chronic neck and upper extremity pain
      emanating as a result of cervical spine pathology. METHODS: The available
      literature of cervical interlaminar epidural injections in managing chronic neck
      and upper extremity pain was reviewed. The quality assessment and clinical
      relevance criteria utilized were the Cochrane Musculoskeletal Review Group
      criteria as utilized for interventional techniques for randomized trials and the
      criteria developed by the Agency for Healthcare Research and Quality (AHRQ)
      criteria for observational studies. The level of evidence was classified as Level
      I, II, or III based on the quality of evidence developed by the U.S. Preventive
      Services Task Force (USPSTF) for therapeutic interventions. Data sources included
      relevant literature of the English language identified through searches of PubMed
      and EMBASE from 1966 to November 2008, and manual searches of bibliographies of
      known primary and review articles. OUTCOME MEASURES: The primary outcome measure
      was pain relief (short-term relief = up to 6 months and long-term > 6 months).
      Secondary outcome measures were improvement in functional status, psychological
      status, return to work, and reduction in opioid intake. RESULTS: The indicated
      evidence is Level II-1 in managing chronic neck and upper extremity pain with
      1C/strong recommendation. LIMITATIONS: The limitations of this systematic review
      include the paucity of literature and lack of randomized trials performed under
      fluoroscopy. CONCLUSION: The results of this systematic evaluation of cervical
      interlaminar epidural injection showed significant effect in relieving chronic
      intractable pain of cervical origin and also providing long-term relief with an
      indicated evidence level of Level II-1.

PMID- 19165301
TI  - Thromboembolic stroke: a rare complication associated with peri-procedural
      management of an epidural steroid injection.
AB  - BACKGROUND: Little attention has been afforded to the potential adverse sequelae
      of withholding anticoagulation therapy in a patient after neuraxial
      interventions. OBJECTIVE: Presenting a case of thromboembolic stroke in a patient
      after holding warfarin for a lumbar epidural steroid injection, previously
      unreported in published literature. The discussion that follows reviews the
      guidelines available to reduce the risk of thromboembolic events in
      anticoagulated patients in the periprocedural period. CASE REPORT: An 81-year-old
      female with radicular pain secondary to spinal stenosis had been seen on 5
      previous occasions for lumbar epidural steroid injections. Prior to each
      procedure warfarin was held for 5-7 days with demonstrable reversal of
      anticoagulation to within the safe limits set for neuraxial techniques by the
      American Society of Regional Anesthesia and Pain Medicine. On the morning
      following the sixth injection the patient was admitted to the hospital for new
      onset slurred speech and left-sided hemiparesis. A computed tomography scan
      established an acute, localized infarct in the distribution of the right middle
      cerebral artery. Her symptoms were non-reversible and permanent. CONCLUSIONS:
      Thromboembolism is a potentially devastating complication associated with atrial
      fibrillation. Twenty percent of thromboembolic events in patients with atrial
      fibrillation are fatal, and greater than 50% result in permanent disability.
      While thromboembolic events following a brief period of normalization of
      coagulation for interventions appear rare, so is the incidence of epidural
      hematomas. Considering the high mortality and permanent rate of disability with
      thromboembolic events associated with atrial fibrillation, perhaps it is time to
      balance our focus on the complications of withholding anticoagulation with those
      of bleeding.

PMID- 19165302
TI  - Lumbar interlaminar epidural injections in managing chronic low back and lower
      extremity pain: a systematic review.
AB  - BACKGROUND: Low back pain with or without lower extremity pain is the most common
      problem among chronic pain disorders with significant economic, societal, and
      health impact. Epidural injections are one of the most commonly performed
      interventions in the United States in managing chronic low back pain. However the
      evidence is highly variable among different techniques utilized - namely
      interlaminar, caudal, transforaminal - and for various conditions, namely -
      intervertebral disc herniation, spinal stenosis, and discogenic pain without disc
      herniation or radiculitis. STUDY DESIGN: A systematic review of lumbar
      interlaminar epidural injections with or without steroids. OBJECTIVE: To evaluate
      the effect of lumbar interlaminar epidural injections with or without steroids in
      managing various types of chronic low back and lower extremity pain emanating as
      a result of disc herniation or radiculitis, spinal stenosis, and chronic
      discogenic pain. METHODS: Review of the literature and methodologic quality
      assessment were performed according to the Cochrane Musculoskeletal Review Group
      Criteria as utilized for interventional techniques for randomized trials and the
      Agency for Healthcare Research and Quality (AHRQ) criteria for observational
      studies. The level of evidence was classified as Level I, II, or III based on the
      quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF)
      for therapeutic interventions. Data sources included relevant literature of the
      English language identified through searches of PubMed and EMBASE from 1966 to
      November 2008, and manual searches of bibliographies of known primary and review
      articles. Results of analysis were performed for multiple conditions separately.
      OUTCOME MEASURES: The primary outcome measure was pain relief (short-term relief
      = up to 6 months and long-term > 6 months). Secondary outcome measures were
      improvement in functional status, psychological status, return to work, and
      reduction in opioid intake. RESULTS: The available literature included only blind
      epidural injections without fluoroscopy. The indicated evidence is positive
      (Level II-2) for short-term relief of pain of disc herniation or radiculitis
      utilizing blind interlaminar epidural steroid injections with lacking of evidence
      with Level III for long-term relief for disc herniation and radiculitis. The
      evidence is lacking with Level III for short and long-term relief for spinal
      stenosis and discogenic pain without radiculitis or disc herniation utilizing
      blind epidural injections. LIMITATIONS: The limitations of this study include
      paucity of literature, lack of quality evidence, lack of fluoroscopic procedures,
      and lack of applicable evidence in contemporary interventional pain management
      practices. CONCLUSION: The evidence based on this systematic review is limited
      for blind interlaminar epidurals in managing all types of pain except for short
      term relief of pain secondary to disc herniation and radiculitis. This evidence
      does not represent contemporary interventional pain management practices and also
      the evidence may not be extrapolated to fluoroscopically directed lumbar
      interlaminar epidural injections.

PMID- 19165303
TI  - Continuous cervical epidural analgesia for rehabilitation after shoulder surgery:
      a retrospective evaluation.
AB  - BACKGROUND: Patients with frozen shoulder who fail conservative therapy need
      surgical treatment and aggressive post-operative rehabilitation. OBJECTIVE: To
      evaluate the effect of continuous cervical epidural analgesia on pain scores and
      range of motion of the shoulder joint in patients undergoing surgery for
      treatment of refractory frozen shoulder. METHODS: Twenty-one patients with
      refractory frozen shoulder who had failed conservative treatment and undergone
      surgical procedure (manipulation under anesthesia or capsular release) were
      identified and the data were collected retrospectively. These patients had
      cervical tunneled epidural catheter (TEC) placement for continuous infusion of a
      mixture of low-dose narcotic and local anesthetics at the time of surgery and
      were discharged home with the catheter in place. They were then involved in an
      active physical therapy program to increase the range of motion of the affected
      shoulder joint. The patients (N = 21) were followed for a median of 4.7 weeks.
      They were assessed for range of motion, function, visual analog pain scores
      (VAS), and opiate use before the surgery and after tunneled epidural catheter
      removal. RESULTS: Statistically significant changes from the time of placement to
      the time of removal of the tunneled epidural catheter (TEC) were observed for VAS
      pain score and range of motion of the shoulder in forward flexion, external
      rotation, and internal rotation. The mean rate of change among the patients for
      pain score, forward flexion, external rotation, and internal rotation was also
      computed. The mean change per week in each of these 4 measurements significantly
      differed from zero. 33 percent of the patients returned to work within one week.
      CONCLUSION: Our data show that the continuous infusion of epidural opioids and
      local anesthetics through a tunneled cervical epidural catheter during the
      rehabilitation phase after shoulder surgery for adhesive capsulitis may be a safe
      and effective tool for post-operative pain control and to facilitate
      rehabilitation.

PMID- 19165304
TI  - Systematic review of the role of sedation in diagnostic spinal interventional
      techniques.
AB  - BACKGROUND: There is ongoing controversy regarding the validity of controlled
      diagnostic blocks due to variability in sensitivity, specificity, and accuracy.
      Consequently, identification of false-positive rates, false-negative rates, and
      placebo responses is crucial. The reasons described for false-positive responses
      to diagnostic anesthetic blocks are many; however, sedation and psychological
      factors have been implied as causes. Further, there is no consensus with regards
      to sedation prior to controlled diagnostic blocks and their influence on the
      accuracy and validity of a diagnosis. STUDY DESIGN: A systematic review of the
      literature evaluating the influence of sedation on diagnostic spinal
      interventional techniques. OBJECTIVES: To systematically assess the quality of
      clinical studies evaluating the diagnostic accuracy of controlled diagnostic
      blocks in the diagnosis of chronic spinal pain. METHODS: A comprehensive
      evaluation of the literature relating to sedation in diagnostic interventional
      techniques was performed. The methodologic quality assessment of the studies was
      carried out by utilizing Agency for Healthcare Research and Quality (AHRQ)
      methodologic quality criteria with scores of 50 or higher included in the
      assessment of the level of evidence. Level of evidence was based on the U.S.
      Preventive Services Task Force (USPSTF) criteria for the assessment of accuracy
      of diagnostic studies. LIMITATIONS: All 3 of the studies were produced by one
      group of authors. Thus paucity of the literature on the subject of facet joint
      pain and the lack of literature on the subjects of discogenic pain and sacroiliac
      joint pain are major limitations. RESULTS: Three studies were identified which
      met inclusion and methodologic assessment quality criteria. Sedation can be a
      confounding factor in a small population of patients specifically if fentanyl is
      employed and non-stringent criteria are followed. Based on the 3 randomized
      double-blind trials with stringent criteria utilizing 80% pain relief and the
      ability to perform prior painful movements without any significant pain following
      the diagnostic injection in evaluation of facet joint pain, the indicated
      evidence is Level II-1. CONCLUSION: This systematic review provides no
      significant evidence of the influence of sedation either with midazolam or
      fentanyl in the evaluation of cervical and lumbar facet joint pain with
      controlled cervical and lumbar facet joint nerve blocks with an indicated
      evidence of Level II-1, with application of stringent criteria of at least 80%
      pain relief and the ability to perform previously painful movements after the
      diagnostic blocks.

PMID- 19165305
TI  - Systematic review of the effectiveness of thermal annular procedures in treating
      discogenic low back pain.
AB  - BACKGROUND: Chronic discogenic low back pain is a common problem with significant
      personal and societal costs. Thermal annular procedures (TAPs) have been
      developed in an effort to provide a minimally invasive treatment for this
      disorder. Multiple techniques utilized are intradiscal electrothermal therapy
      (IDET), radiofrequency annuloplasty, and intradiscal biacuplasty (IDB). However,
      these treatments continue to be controversial, coupled with a paucity of
      evidence. STUDY DESIGN: A systematic review of the literature evaluating the
      efficacy or effectiveness of TAPs. OBJECTIVE: To determine the effectiveness of
      TAPs in reducing low back pain in patients with intradiscal disorders. METHODS: A
      comprehensive evaluation of the literature relating to TAPs was performed. The
      literature was evaluated according to Cochrane Review criteria for randomized
      controlled trials (RCTs) and according to the Agency for Healthcare Research and
      Quality (AHRQ) criteria for observational studies. The level of evidence was
      classified as Level I, II, or III based on the quality of evidence developed by
      the U.S. Preventive Services Task Force (USPSTF). Pain relief was the primary
      outcome measure. Other outcome measures were functional improvement, improvement
      of psychological status, and return to work. Data sources included relevant
      literature of the English language identified through searches of PubMed, EMBASE,
      the Cochrane Library, and the Database of Reviews of Effectiveness (DARE).
      OUTCOME MEASURES: Short-term effectiveness was defined as one-year or less and
      long-term effectiveness was defined as greater than one-year. RESULTS: Systematic
      review of IDET identified 2 RCTs and 16 observational studies with an indicated
      evidence of Level II-2. Systematic review of radiofrequency annuloplasty
      identified no RCTs but 2 observational studies with an uncertain evidence of
      Level II-3. Systematic review of IDB identified one pilot study. The level of
      evidence is lacking with Level III. LIMITATIONS: The limitations of this review
      include paucity of the literature and lack of evidence with internal validity and
      generalizability. CONCLUSION: IDET offers functionally significant relief in
      approximately one-half of appropriately chosen chronic discogenic low back pain
      patients. There is minimal evidence supporting the use of radiofrequency
      annuloplasty and IDB.

PMID- 19165306
TI  - Systematic review of therapeutic lumbar transforaminal epidural steroid
      injections.
AB  - BACKGROUND: Epidural injection of corticosteroids is one of the most commonly
      used interventions in managing chronic spinal pain. The transforaminal route to
      the lumbar epidural space for steroid injection has gained rapid and widespread
      acceptance for the treatment of lumbar and leg pain. However, there are few well
      designed randomized, controlled studies to determine the effectiveness of
      epidural injections. The role and value of transforaminal lumbar epidural steroid
      injections is still questioned. STUDY DESIGN: A systematic review of
      transforaminal epidural injection therapy for low back and lower extremity pain.
      OBJECTIVE: To evaluate the effect of transforaminal lumbar epidural steroid
      injections in managing lumbar (low-back) and sciatica (leg) pain. METHODS: The
      available literature of lumbar transforaminal epidural injections in managing
      chronic low back and lower extremity pain was reviewed. The quality assessment
      and clinical relevance criteria utilized were the Cochrane Musculoskeletal Review
      Group criteria as utilized for interventional techniques for randomized trials
      and the criteria developed by the Agency for Healthcare Research and Quality
      (AHRQ) criteria for observational studies. The level of evidence was classified
      as Level I, II, or III based on the quality of evidence developed by the U.S.
      Preventive Services Task Force (USPSTF). Data sources included relevant
      literature of the English language identified through searches of PubMed and
      EMBASE from 1966 to November 2008, and manual searches of the bibliographies of
      known primary and review articles. OUTCOME MEASURES: The primary outcome measure
      was pain relief (short-term relief = up to 6 months and long-term > 6 months).
      Secondary outcome measures were improvement in functional status, psychological
      status, return to work, and reduction in opioid intake. RESULTS: The indicated
      evidence is Level II-1 for short-term relief and Level II-2 for long-term relief
      in managing chronic low back and lower extremity pain. LIMITATIONS: The
      limitations of this systematic review include the paucity of literature.
      CONCLUSION: The indicated evidence for transforaminal lumbar epidural steroid
      injections is Level II-1 for short-term relief and Level II-2 for long-term
      improvement in the management of lumbar nerve root and low back pain.

PMID- 19165307
TI  - Transoral approach to CT-guided C2 interventions.
AB  - BACKGROUND: Lesions involving C2 are unique as it is challenging to approach
      these lesions. The transoral approach to C2 lesions has been extensively used by
      surgeons and increasingly used by interventional radiologists for vertebroplasty
      as it is safer and less demanding than other approaches like anterolateral and
      posterolateral (transpedicular). However, using this approach for image-guided
      biopsies is little described in literature with a few cases described so far
      being under fluoroscopic guidance. We describe a series of 5 procedures using
      transoral approach - 4 biopsies (and one vertebroplasty that was published
      earlier) on C2 lesions under CT guidance. To our knowledge, our series is the
      first one where the transoral biopsies were performed using Computed Tomography
      (CT) guidance. OBJECTIVE: To describe our initial experience with the transoral
      approach to image-guided biopsies on C2 vertebra and its relative advantages and
      disadvantages. METHODS: We performed 5 procedures - 4 biopsies (and one
      vertebroplasty published earlier) on different types of lesions involving C2,
      through the transoral approach, using CT guidance under general anesthesia and
      appropriate precautions to reduce potential complications like infection,
      hemorrhage, etc. RESULTS: The procedures were well tolerated by the patients
      without any complications, immediately as well as at follow-up. All the biopsies
      in our series were technically successful without any minor or major
      complications. The biopsy yield was 50% which may be due to the thinner needles
      used. CONCLUSION: CT-guided transoral approach to biopsies on C2 lesions is a
      direct, safe, and precise technique when performed with appropriate precautions.

PMID- 19165308
TI  - Prevalence of side effects of prolonged low or moderate dose opioid therapy with
      concomitant benzodiazepine and/or antidepressant therapy in chronic non-cancer
      pain.
AB  - BACKGROUND: Opioid use in the management of chronic pain is widespread in chronic
      pain settings. Opioid prescriptions for non-cancer pain and overall opioid sales
      have been soaring with the increasing nonmedical use of opioids in the United
      States. Prolonged use of high dose opioids has been associated with adverse
      consequences including tolerance, abuse, addiction, hyperalgesia, hormonal
      effects, and immunosuppression. Studies of high dose therapy have shown pain
      relief with a 30% decrease in the intensity of pain and that only 44% of the
      patients continue the treatment between 7 and 24 months. However, there is no
      data available on the prevalence of side effects associated with low or moderate
      dose opioid use in chronic non-cancer pain when administered in conjunction with
      interventional techniques. OBJECTIVE: To evaluate the prevalence of side effects,
      of low or moderate dose opioid therapy with or without benzodiazepines,
      antidepressants, and their combinations. METHODS: The evaluation was conducted by
      interviewing 1,000 patients on stable doses of opioids, with or without
      benzodiazepines, antidepressants, and their combinations. Patients were
      categorized into 4 groups with Group 1 receiving opioids only (n = 143), Group 2
      receiving opioids and benzodiazepines (n = 159), Group 3 receiving opioids and
      antidepressants (n = 113), and Group 4 received opioids, benzodiazepines, and
      antidepressants (n = 118). RESULTS: Inclusion criteria was met in 533 patients
      receiving opioid therapy for longer than 6 months. The incidence of side effects
      in Group 1 was 18%, in Group 2 was 8%, in Group 3 was 17%, and in Group 4 was
      14%. The most frequent complications were in patients receiving methadone (52%)
      followed by oxycodone (41%) and morphine (36%). Patients receiving hydrocodone
      had the least incidences of side effects with 7.5%. There were no significant
      differences noted based on the duration of therapy, age of the patient, and
      gender. Severe side effects accounted for only 14 of 137 instances. LIMITATIONS:
      Limitations of this study include the inability to incorporate multiple other
      drugs due to complicated nature with multiple groups and data collection and
      analysis. The other limitation is that the proportion of patients receiving
      methadone, oxycodone, morphine, and propoxyphene was low compared to hydrocodone
      with 77% of the patients. CONCLUSION: Moderate or low dose opioid therapy in
      conjunction with or without benzodiazepines, antidepressants, or in combinations
      are associated with minor side effects.

PMID- 19165309
TI  - Potential analgesic mechanisms of acetaminophen.
AB  - Despite nearing the end of the decade of pain research, the analgesic mechanisms
      of one of the most widely used and popular analgesics remains uncertain.
      Acetaminophen (APAP) (paracetamol [PARA]) has been used clinically for over a
      half of a century and although clinicians seem to be comfortable with its
      benefits, risks, and limitations, they still remain in the dark as to precisely
      what is providing its pain relief. What does seem clearer is that the predominant
      mechanisms of APAP's analgesic effects are in the central nervous system (CNS).
      Although, which central effects are largely responsible for APAP's effects on
      pain continue to be uncertain. Perhaps, the most accepted theory is that of
      APAP's positive effects on the serotonergic descending inhibitory pathways.
      However, interactions with opioidergic systems, eicosanoid systems, and/or nitric
      oxide containing pathways may be involved as well. Furthermore, endocannabinoid
      signaling may play a role in APAP's activation of the serotonergic descending
      inhibitory pathways. A greater understanding of APAP's analgesic mechanisms may
      promote optimal utilization of analgesic polypharmacy.

PMID- 19165310
TI  - Dehydration: cause of acute renal failure.

PMID- 19165312
TI  - Case report: modified latissimus dorsi muscle transfer for radial palsy:
      presentation of a new technique.
AB  - OBJECTIVE: The latissimus dorsi muscle transfer finger and wrist extension is a
      well-known procedure for patients needing replantation or in brachial plexus
      injuries. To increase the length of the transferred muscle to reach to the finger
      and wrist extensors, the other authors suggest extending the muscle length by
      incorporating the iliac crest fascia, which not only prolongs the operation time
      but also minimizes the chances of a healthy and viable muscle-tendon junction. We
      present a modification of the standard latissimus dorsi transfer whereby the
      whole muscle (not partial harvest) is transferred and extended by tendon graft to
      minimize the distal muscle-tendon problems and inefficient muscle excursion
      commonly encountered with the thus far reported techniques. METHODS: In a 12-year
      period (1996-2008), 5 patients were treated. Guidelines for patient selection
      were (1) complete high radial nerve palsy with no simpler solution to address the
      problem, (2) supple joints and gliding tendons, (3) good patient motivation, and
      (4) free muscle transfer not feasible or risky. RESULTS: Five male patients aged
      18 to 45 were treated for the absence of wrist and finger extension due to radial
      nerve damage or extensor group destruction. They were able to use the transferred
      muscle for extension with minimal training and physiotherapy. CONCLUSION: (1)
      Transferring the whole muscle ensures a complete neural arborization and better
      excursion. (2) It ensures a safe tendon suture wherein the muscle-tendon unit is
      far from the distal end of the skin flap (less possibility of necrosis).

PMID- 19165313
TI  - Astrocytic mechanisms explaining neural-activity-induced shrinkage of
      extraneuronal space.
AB  - Neuronal stimulation causes approximately 30% shrinkage of the extracellular
      space (ECS) between neurons and surrounding astrocytes in grey and white matter
      under experimental conditions. Despite its possible implications for a proper
      understanding of basic aspects of potassium clearance and astrocyte function, the
      phenomenon remains unexplained. Here we present a dynamic model that accounts for
      current experimental data related to the shrinkage phenomenon in wild-type as
      well as in gene knockout individuals. We find that neuronal release of potassium
      and uptake of sodium during stimulation, astrocyte uptake of potassium, sodium,
      and chloride in passive channels, action of the Na/K/ATPase pump, and osmotically
      driven transport of water through the astrocyte membrane together seem sufficient
      for generating ECS shrinkage as such. However, when taking into account ECS and
      astrocyte ion concentrations observed in connection with neuronal stimulation,
      the actions of the Na(+)/K(+)/Cl(-) (NKCC1) and the Na(+)/HCO(3) (-) (NBC)
      cotransporters appear to be critical determinants for achieving observed
      quantitative levels of ECS shrinkage. Considering the current state of knowledge,
      the model framework appears sufficiently detailed and constrained to guide future
      key experiments and pave the way for more comprehensive astroglia-neuron
      interaction models for normal as well as pathophysiological situations.

PMID- 19165314
TI  - Model-based therapeutic correction of hypothalamic-pituitary-adrenal axis
      dysfunction.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is a major system maintaining body
      homeostasis by regulating the neuroendocrine and sympathetic nervous systems as
      well modulating immune function. Recent work has shown that the complex dynamics
      of this system accommodate several stable steady states, one of which corresponds
      to the hypocortisol state observed in patients with chronic fatigue syndrome
      (CFS). At present these dynamics are not formally considered in the development
      of treatment strategies. Here we use model-based predictive control (MPC)
      methodology to estimate robust treatment courses for displacing the HPA axis from
      an abnormal hypocortisol steady state back to a healthy cortisol level. This
      approach was applied to a recent model of HPA axis dynamics incorporating
      glucocorticoid receptor kinetics. A candidate treatment that displays robust
      properties in the face of significant biological variability and measurement
      uncertainty requires that cortisol be further suppressed for a short period until
      adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be
      discontinued, and the HPA axis will naturally progress to a stable attractor
      defined by normal hormone levels. Suppression of biologically available cortisol
      may be achieved through the use of binding proteins such as CBG and certain
      metabolizing enzymes, thus offering possible avenues for deployment in a clinical
      setting. Treatment strategies can therefore be designed that maximally exploit
      system dynamics to provide a robust response to treatment and ensure a positive
      outcome over a wide range of conditions. Perhaps most importantly, a treatment
      course involving further reduction in cortisol, even transient, is quite
      counterintuitive and challenges the conventional strategy of supplementing
      cortisol levels, an approach based on steady-state reasoning.

PMID- 19165315
TI  - Joint evolutionary trees: a large-scale method to predict protein interfaces
      based on sequence sampling.
AB  - The Joint Evolutionary Trees (JET) method detects protein interfaces, the core
      residues involved in the folding process, and residues susceptible to site
      directed mutagenesis and relevant to molecular recognition. The approach, based
      on the Evolutionary Trace (ET) method, introduces a novel way to treat
      evolutionary information. Families of homologous sequences are analyzed through a
      Gibbs-like sampling of distance trees to reduce effects of erroneous multiple
      alignment and impacts of weakly homologous sequences on distance tree
      construction. The sampling method makes sequence analysis more sensitive to
      functional and structural importance of individual residues by avoiding effects
      of the overrepresentation of highly homologous sequences and improves
      computational efficiency. A carefully designed clustering method is parametrized
      on the target structure to detect and extend patches on protein surfaces into
      predicted interaction sites. Clustering takes into account residues' physical
      chemical properties as well as conservation. Large-scale application of JET
      requires the system to be adjustable for different datasets and to guarantee
      predictions even if the signal is low. Flexibility was achieved by a careful
      treatment of the number of retrieved sequences, the amino acid distance between
      sequences, and the selective thresholds for cluster identification. An iterative
      version of JET (iJET) that guarantees finding the most likely interface residues
      is proposed as the appropriate tool for large-scale predictions. Tests are
      carried out on the Huang database of 62 heterodimer, homodimer, and transient
      complexes and on 265 interfaces belonging to signal transduction proteins,
      enzymes, inhibitors, antibodies, antigens, and others. A specific set of proteins
      chosen for their special functional and structural properties illustrate JET
      behavior on a large variety of interactions covering proteins, ligands, DNA, and
      RNA. JET is compared at a large scale to ET and to Consurf, Rate4Site,
      siteFiNDER|3D, and SCORECONS on specific structures. A significant improvement in
      performance and computational efficiency is shown.

PMID- 19165316
TI  - Computational modeling of the hematopoietic erythroid-myeloid switch reveals
      insights into cooperativity, priming, and irreversibility.
AB  - Hematopoietic stem cell lineage choices are decided by genetic networks that are
      turned ON/OFF in a switch-like manner. However, prior to lineage commitment,
      genes are primed at low expression levels. Understanding the underlying molecular
      circuitry in terms of how it governs both a primed state and, at the other
      extreme, a committed state is of relevance not only to hematopoiesis but also to
      developmental systems in general. We develop a computational model for the
      hematopoietic erythroid-myeloid lineage decision, which is determined by a
      genetic switch involving the genes PU.1 and GATA-1. Dynamical models based upon
      known interactions between these master genes, such as mutual antagonism and
      autoregulation, fail to make the system bistable, a desired feature for robust
      lineage determination. We therefore suggest a new mechanism involving a cofactor
      that is regulated as well as recruited by one of the master genes to bind to the
      antagonistic partner that is necessary for bistability and hence switch-like
      behavior. An interesting fallout from this architecture is that suppression of
      the cofactor through external means can lead to a loss of cooperativity, and
      hence to a primed state for PU.1 and GATA-1. The PU.1-GATA-1 switch also
      interacts with another mutually antagonistic pair, C/EBPalpha-FOG-1. The latter
      pair inherits the state of its upstream master genes and further reinforces the
      decision due to several feedback loops, thereby leading to irreversible
      commitment. The genetic switch, which handles the erythroid-myeloid lineage
      decision, is an example of a network that implements both a primed and a
      committed state by regulating cooperativity through recruitment of cofactors.
      Perturbing the feedback between the master regulators and downstream targets
      suggests potential reprogramming strategies. The approach points to a framework
      for lineage commitment studies in general and could aid the search for lineage
      determining genes.

PMID- 19165317
TI  - Heterochromatic threads connect oscillating chromosomes during prometaphase I in
      Drosophila oocytes.
AB  - In Drosophila oocytes achiasmate homologs are faithfully segregated to opposite
      poles at meiosis I via a process referred to as achiasmate homologous
      segregation. We observed that achiasmate homologs display dynamic movements on
      the meiotic spindle during mid-prometaphase. An analysis of living prometaphase
      oocytes revealed both the rejoining of achiasmate X chromosomes initially located
      on opposite half-spindles and the separation toward opposite poles of two X
      chromosomes that were initially located on the same half spindle. When the two
      achiasmate X chromosomes were positioned on opposite halves of the spindle their
      kinetochores appeared to display proper co-orientation. However, when both Xs
      were located on the same half spindle their kinetochores appeared to be oriented
      in the same direction. Thus, the prometaphase movement of achiasmate chromosomes
      is a congression-like process in which the two homologs undergo both separation
      and rejoining events that result in the either loss or establishment of proper
      kinetochore co-orientation. During this period of dynamic chromosome movement,
      the achiasmate homologs were connected by heterochromatic threads that can span
      large distances relative to the length of the developing spindle. Additionally,
      the passenger complex proteins Incenp and Aurora B appeared to localize to these
      heterochromatic threads. We propose that these threads assist in the rejoining of
      homologs and the congression of the migrating achiasmate homologs back to the
      main chromosomal mass prior to metaphase arrest.

PMID- 19165318
TI  - Natural variation in an ABC transporter gene associated with seed size evolution
      in tomato species.
AB  - Seed size is a key determinant of evolutionary fitness in plants and is a trait
      that often undergoes tremendous changes during crop domestication. Seed size is
      most often quantitatively inherited, and it has been shown that Sw4.1 is one of
      the most significant quantitative trait loci (QTLs) underlying the evolution of
      seed size in the genus Solanum-especially in species related to the cultivated
      tomato. Using a combination of genetic, developmental, molecular, and transgenic
      techniques, we have pinpointed the cause of the Sw4.1 QTL to a gene encoding an
      ABC transporter gene. This gene exerts its control on seed size, not through the
      maternal plant, but rather via gene expression in the developing zygote.
      Phenotypic effects of allelic variation at Sw4.1 are manifested early in seed
      development at stages corresponding to the rapid deposition of starch and lipids
      into the endospermic cells. Through synteny, we have identified the Arabidopsis
      Sw4.1 ortholog. Mutagenesis has revealed that this ortholog is associated with
      seed length variation and fatty acid deposition in seeds, raising the possibility
      that the ABC transporter may modulate seed size variation in other species.
      Transcription studies show that the ABC transporter gene is expressed not only in
      seeds, but also in other tissues (leaves and roots) and, thus, may perform
      functions in parts of the plants other than developing seeds. Cloning and
      characterization of the Sw4.1 QTL gives new insight into how plants change seed
      during evolution and may open future opportunities for modulating seed size in
      crop plants for human purposes.

PMID- 19165320
TI  - Consistency analysis of redundant probe sets on affymetrix three-prime expression
      arrays and applications to differential mRNA processing.
AB  - Affymetrix three-prime expression microarrays contain thousands of redundant
      probe sets that interrogate different regions of the same gene. Differential
      expression analysis methods rarely consider probe redundancy, which can lead to
      inaccurate inference about overall gene expression or cause investigators to
      overlook potentially valuable information about differential regulation of
      variant mRNA products. We investigated the behaviour and consistency of redundant
      probe sets in a publicly-available data set containing samples from mouse brain
      amygdala and hippocampus and asked how applying filtering methods to the data
      affected consistency of results obtained from redundant probe sets. A genome
      based filter that screens and groups probe sets according to their overlapping
      genomic alignments significantly improved redundant probe set consistency.
      Screening based on qualitative Present-Absent calls from MAS5 also improved
      consistency. However, even after applying these filters, many redundant probe
      sets showed significant fold-change differences relative to each other,
      suggesting differential regulation of alternative transcript production. Visual
      inspection of these loci using an interactive genome visualization tool
      (igb.bioviz.org) exposed thirty putative examples of differential regulation of
      alternative splicing or polyadenylation across brain regions in mouse. This work
      demonstrates how P/A-call and genome-based filtering can improve consistency
      among redundant probe sets while at the same time exposing possible differential
      regulation of RNA processing pathways across sample types.

PMID- 19165319
TI  - Organised genome dynamics in the Escherichia coli species results in highly
      diverse adaptive paths.
AB  - The Escherichia coli species represents one of the best-studied model organisms,
      but also encompasses a variety of commensal and pathogenic strains that diversify
      by high rates of genetic change. We uniformly (re-) annotated the genomes of 20
      commensal and pathogenic E. coli strains and one strain of E. fergusonii (the
      closest E. coli related species), including seven that we sequenced to
      completion. Within the approximately 18,000 families of orthologous genes, we
      found approximately 2,000 common to all strains. Although recombination rates are
      much higher than mutation rates, we show, both theoretically and using
      phylogenetic inference, that this does not obscure the phylogenetic signal, which
      places the B2 phylogenetic group and one group D strain at the basal position.
      Based on this phylogeny, we inferred past evolutionary events of gain and loss of
      genes, identifying functional classes under opposite selection pressures. We
      found an important adaptive role for metabolism diversification within group B2
      and Shigella strains, but identified few or no extraintestinal virulence-specific
      genes, which could render difficult the development of a vaccine against
      extraintestinal infections. Genome flux in E. coli is confined to a small number
      of conserved positions in the chromosome, which most often are not associated
      with integrases or tRNA genes. Core genes flanking some of these regions show
      higher rates of recombination, suggesting that a gene, once acquired by a strain,
      spreads within the species by homologous recombination at the flanking genes.
      Finally, the genome's long-scale structure of recombination indicates lower
      recombination rates, but not higher mutation rates, at the terminus of
      replication. The ensuing effect of background selection and biased gene
      conversion may thus explain why this region is A+T-rich and shows high sequence
      divergence but low sequence polymorphism. Overall, despite a very high gene flow,
      genes co-exist in an organised genome.

PMID- 19165321
TI  - Impact of the Spanish smoking law on exposure to second-hand smoke and
      respiratory health in hospitality workers: a cohort study.
AB  - BACKGROUND: A smoke-free law came into effect in Spain on 1st January 2006,
      affecting all enclosed workplaces except hospitality venues, whose proprietors
      can choose among totally a smoke-free policy, a partial restriction with
      designated smoking areas, or no restriction on smoking on the premises. We aimed
      to evaluate the impact of the law among hospitality workers by assessing second
      hand smoke (SHS) exposure and the frequency of respiratory symptoms before and
      one year after the ban. METHODS AND FINDING: We formed a baseline cohort of 431
      hospitality workers in Spain and 45 workers in Portugal and Andorra. Of them, 318
      (66.8%) were successfully followed up 12 months after the ban, and 137 nonsmokers
      were included in this analysis. We obtained self-reported exposure to SHS and the
      presence of respiratory symptoms, and collected saliva samples for cotinine
      measurement. Salivary cotinine decreased by 55.6% after the ban among nonsmoker
      workers in venues where smoking was totally prohibited (from median of 1.6 ng/ml
      before to 0.5 ng/ml, p<0.01). Cotinine concentration decreased by 27.6% (p =
      0.068) among workers in venues with designated smoking areas, and by 10.7% (p =
      0.475) among workers in venues where smoking was allowed. In Portugal and
      Andorra, no differences between cotinine concentration were found before (1.2
      ng/ml) and after the ban (1.2 ng/ml). In Spain, reported respiratory symptom
      declined significantly (by 71.9%; p<0.05) among workers in venues that became
      smoke-free. After adjustment for potential confounders, salivary cotinine and
      respiratory symptoms decreased significantly among workers in Spanish hospitality
      venues where smoking was totally banned. CONCLUSIONS: Among nonsmoker hospitality
      workers in bars and restaurants where smoking was allowed, exposure to SHS after
      the ban remained similar to pre-law levels. The partial restrictions on smoking
      in Spanish hospitality venues do not sufficiently protect hospitality workers
      against SHS or its consequences for respiratory health.

PMID- 19165322
TI  - Immunization with single-cycle SIV significantly reduces viral loads after an
      intravenous challenge with SIV(mac)239.
AB  - Strains of simian immunodeficiency virus (SIV) that are limited to a single cycle
      of infection were evaluated for the ability to elicit protective immunity against
      wild-type SIV(mac)239 infection of rhesus macaques by two different vaccine
      regimens. Six animals were inoculated at 8-week intervals with 6 identical doses
      consisting of a mixture of three different envelope variants of single-cycle SIV
      (scSIV). Six additional animals were primed with a mixture of cytoplasmic domain
      truncated envelope variants of scSIV and boosted with two doses of vesicular
      stomatitis virus glycoprotein (VSV G) trans-complemented scSIV. While both
      regimens elicited detectable virus-specific T cell responses, SIV-specific T cell
      frequencies were more than 10-fold higher after boosting with VSV G trans
      complemented scSIV (VSV G scSIV). Broad T cell recognition of multiple viral
      antigens and Gag-specific CD4(+) T cell responses were also observed after
      boosting with VSV G scSIV. With the exception of a single animal in the repeated
      immunization group, all of the animals became infected following an intravenous
      challenge with SIV(mac)239. However, significantly lower viral loads and higher
      memory CD4(+) T cell counts were observed in both immunized groups relative to an
      unvaccinated control group. Indeed, both scSIV immunization regimens resulted in
      containment of SIV(mac)239 replication after challenge that was as good as, if
      not better than, what has been achieved by other non-persisting vaccine vectors
      that have been evaluated in this challenge model. Nevertheless, the extent of
      protection afforded by scSIV was not as good as typically conferred by persistent
      infection with live, attenuated SIV. These observations have potentially
      important implications to the design of an effective AIDS vaccine, since they
      suggest that ongoing stimulation of virus-specific immune responses may be
      essential to achieving the degree of protection afforded by live, attenuated SIV.

PMID- 19165323
TI  - An inhibitory antibody blocks interactions between components of the malarial
      invasion machinery.
AB  - Host cell invasion by apicomplexan pathogens such as the malaria parasite
      Plasmodium spp. and Toxoplasma gondii involves discharge of proteins from
      secretory organelles called micronemes and rhoptries. In Toxoplasma a protein
      complex comprising the microneme apical membrane antigen 1 (AMA1), two rhoptry
      neck proteins, and a protein called Ts4705, localises to the moving junction, a
      region of close apposition between parasite and host cell during invasion.
      Antibodies against AMA1 prevent invasion and are protective in vivo, and so AMA1
      is of widespread interest as a malaria vaccine candidate. Here we report that the
      AMA1 complex identified in Toxoplasma is conserved in Plasmodium falciparum. We
      demonstrate that the invasion-inhibitory monoclonal antibody (mAb) 4G2, which
      recognises P. falciparum AMA1 (PfAMA1), cannot bind when PfAMA1 is in a complex
      with its partner proteins. We further show that a single completely conserved
      PfAMA1 residue, Tyr251, lying within a conserved hydrophobic groove adjacent to
      the mAb 4G2 epitope, is required for complex formation. We propose that mAb 4G2
      inhibits invasion by preventing PfAMA1 from interacting with other components of
      the invasion complex. Our findings should aid the rational design of subunit
      malaria vaccines based on PfAMA1.

PMID- 19165324
TI  - Ca extrusion by NCX is compromised in olfactory sensory neurons of OMP mice.
AB  - BACKGROUND: The role of olfactory marker protein (OMP), a hallmark of mature
      olfactory sensory neurons (OSNs), has been poorly understood since its discovery.
      The electrophysiological and behavioral phenotypes of OMP knockout mice indicated
      that OMP influences olfactory signal transduction. However, the mechanism by
      which this occurs remained unknown. PRINCIPAL FINDINGS: We used intact olfactory
      epithelium obtained from WT and OMP(-/-) mice to monitor the Ca(2+) dynamics
      induced by the activation of cyclic nucleotide-gated channels, voltage-operated
      Ca(2+) channels, or Ca(2+) stores in single dendritic knobs of OSNs. Our data
      suggested that OMP could act to modulate the Ca(2+)-homeostasis in these neurons
      by influencing the activity of the plasma membrane Na(+)/Ca(2+)-exchanger (NCX).
      Immunohistochemistry verifies colocalization of NCX1 and OMP in the cilia and
      knobs of OSNs. To test the role of NCX activity, we compared the kinetics of
      Ca(2+) elevation by stimulating the reverse mode of NCX in both WT and OMP(-/-)
      mice. The resulting Ca(2+) responses indicate that OMP facilitates NCX activity
      and allows rapid Ca(2+) extrusion from OSN knobs. To address the mechanism by
      which OMP influences NCX activity in OSNs we studied protein-peptide interactions
      in real-time using surface plasmon resonance technology. We demonstrate the
      direct interaction of the XIP regulatory-peptide of NCX with calmodulin (CaM).
      CONCLUSIONS: Since CaM also binds to the Bex protein, an interacting protein
      partner of OMP, these observations strongly suggest that OMP can influence CaM
      efficacy and thus alters NCX activity by a series of protein-protein
      interactions.

PMID- 19165325
TI  - Inflammatory genital infections mitigate a severe genetic bottleneck in
      heterosexual transmission of subtype A and C HIV-1.
AB  - The HIV-1 epidemic in sub-Saharan Africa is driven largely by heterosexual
      transmission of non-subtype B viruses, of which subtypes C and A are predominant.
      Previous studies of subtype B and subtype C transmission pairs have suggested
      that a single variant from the chronically infected partner can establish
      infection in their newly infected partner. However, in subtype A infected
      individuals from a sex worker cohort and subtype B individuals from STD clinics,
      infection was frequently established by multiple variants. This study examined
      over 1750 single-genome amplified viral sequences derived from epidemiologically
      linked subtype C and subtype A transmission pairs very early after infection. In
      90% (18/20) of the pairs, HIV-1 infection is initiated by a single viral variant
      that is derived from the quasispecies of the transmitting partner. In addition,
      the virus initiating infection in individuals who were infected by someone other
      than their spouse was characterized to determine if genital infections mitigated
      the severe genetic bottleneck observed in a majority of epidemiologically linked
      heterosexual HIV-1 transmission events. In nearly 50% (3/7) of individuals
      infected by someone other than their spouse, multiple genetic variants from a
      single individual established infection. A statistically significant association
      was observed between infection by multiple genetic variants and an inflammatory
      genital infection in the newly infected individual. Thus, in the vast majority of
      HIV-1 transmission events in cohabiting heterosexual couples, a single genetic
      variant establishes infection. Nevertheless, this severe genetic bottleneck can
      be mitigated by the presence of inflammatory genital infections in the at risk
      partner, suggesting that this restriction on genetic diversity is imposed in
      large part by the mucosal barrier.

PMID- 19165326
TI  - Copy number variation of CCL3-like genes affects rate of progression to simian
      AIDS in Rhesus Macaques (Macaca mulatta).
AB  - Variation in genes underlying host immunity can lead to marked differences in
      susceptibility to HIV infection among humans. Despite heavy reliance on non-human
      primates as models for HIV/AIDS, little is known about which host factors are
      shared and which are unique to a given primate lineage. Here, we investigate
      whether copy number variation (CNV) at CCL3-like genes (CCL3L), a key genetic
      host factor for HIV/AIDS susceptibility and cell-mediated immune response in
      humans, is also a determinant of time until onset of simian-AIDS in rhesus
      macaques. Using a retrospective study of 57 rhesus macaques experimentally
      infected with SIVmac, we find that CCL3L CNV explains approximately 18% of the
      variance in time to simian-AIDS (p<0.001) with lower CCL3L copy number
      associating with more rapid disease course. We also find that CCL3L copy number
      varies significantly (p<10(-6)) among rhesus subpopulations, with Indian-origin
      macaques having, on average, half as many CCL3L gene copies as Chinese-origin
      macaques. Lastly, we confirm that CCL3L shows variable copy number in humans and
      chimpanzees and report on CCL3L CNV within and among three additional primate
      species. On the basis of our findings we suggest that (1) the difference in
      population level copy number may explain previously reported observations of
      longer post-infection survivorship of Chinese-origin rhesus macaques, (2)
      stratification by CCL3L copy number in rhesus SIV vaccine trials will increase
      power and reduce noise due to non-vaccine-related differences in survival, and
      (3) CCL3L CNV is an ancestral component of the primate immune response and,
      therefore, copy number variation has not been driven by HIV or SIV per se.

PMID- 19165327
TI  - Order and disorder during Escherichia coli divergence.

PMID- 19165328
TI  - A Legionella pneumophila effector protein encoded in a region of genomic
      plasticity binds to Dot/Icm-modified vacuoles.
AB  - Legionella pneumophila is an opportunistic pathogen that can cause a severe
      pneumonia called Legionnaires' disease. In the environment, L. pneumophila is
      found in fresh water reservoirs in a large spectrum of environmental conditions,
      where the bacteria are able to replicate within a variety of protozoan hosts. To
      survive within eukaryotic cells, L. pneumophila require a type IV secretion
      system, designated Dot/Icm, that delivers bacterial effector proteins into the
      host cell cytoplasm. In recent years, a number of Dot/Icm substrate proteins have
      been identified; however, the function of most of these proteins remains unknown,
      and it is unclear why the bacterium maintains such a large repertoire of
      effectors to promote its survival. Here we investigate a region of the L.
      pneumophila chromosome that displays a high degree of plasticity among four
      sequenced L. pneumophila strains. Analysis of GC content suggests that several
      genes encoded in this region were acquired through horizontal gene transfer.
      Protein translocation studies establish that this region of genomic plasticity
      encodes for multiple Dot/Icm effectors. Ectopic expression studies in mammalian
      cells indicate that one of these substrates, a protein called PieA, has unique
      effector activities. PieA is an effector that can alter lysosome morphology and
      associates specifically with vacuoles that support L. pneumophila replication. It
      was determined that the association of PieA with vacuoles containing L.
      pneumophila requires modifications to the vacuole mediated by other Dot/Icm
      effectors. Thus, the localization properties of PieA reveal that the Dot/Icm
      system has the ability to spatially and temporally control the association of an
      effector with vacuoles containing L. pneumophila through activities mediated by
      other effector proteins.

PMID- 19165329
TI  - An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation
      and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans.
AB  - The nature of toxic effects exerted on neurons by misfolded proteins, occurring
      in a number of neurodegenerative diseases, is poorly understood. One approach to
      this problem is to measure effects when such proteins are expressed in
      heterologous neurons. We report on effects of an ALS-associated, misfolding-prone
      mutant human SOD1, G85R, when expressed in the neurons of Caenorhabditis elegans.
      Stable mutant transgenic animals, but not wild-type human SOD1 transgenics,
      exhibited a strong locomotor defect associated with the presence, specifically in
      mutant animals, of both soluble oligomers and insoluble aggregates of G85R
      protein. A whole-genome RNAi screen identified chaperones and other components
      whose deficiency increased aggregation and further diminished locomotion. The
      nature of the locomotor defect was investigated. Mutant animals were resistant to
      paralysis by the cholinesterase inhibitor aldicarb, while exhibiting normal
      sensitivity to the cholinergic agonist levamisole and normal muscle morphology.
      When fluorescently labeled presynaptic components were examined in the dorsal
      nerve cord, decreased numbers of puncta corresponding to neuromuscular junctions
      were observed in mutant animals and brightness was also diminished. At the EM
      level, mutant animals exhibited a reduced number of synaptic vesicles.
      Neurotoxicity in this system thus appears to be mediated by misfolded SOD1 and is
      exerted on synaptic vesicle biogenesis and/or trafficking.

PMID- 19165330
TI  - Residues clustered in the light-sensing knot of phytochrome B are necessary for
      conformer-specific binding to signaling partner PIF3.
AB  - The bHLH transcription factor, Phytochrome Interacting Factor 3 (PIF3), interacts
      specifically with the photoactivated, Pfr, form of Arabidopsis phytochrome B
      (phyB). This interaction induces PIF3 phosphorylation and degradation in vivo and
      modulates phyB-mediated seedling deetiolation in response to red light. To
      identify missense mutations in the phyB N-terminal domain that disrupt this
      interaction, we developed a yeast reverse-hybrid screen. Fifteen individual
      mutations identified in this screen, or in previous genetic screens for
      Arabidopsis mutants showing reduced sensitivity to red light, were shown to also
      disrupt light-induced binding of phyB to PIF3 in in vitro co-immunoprecipitation
      assays. These phyB missense mutants fall into two general classes: Class I
      (eleven mutants) containing those defective in light signal perception, due to
      aberrant chromophore attachment or photoconversion, and Class II (four mutants)
      containing those normal in signal perception, but defective in the capacity to
      transduce this signal to PIF3. By generating a homology model for the three
      dimensional structure of the Arabidopsis phyB chromophore-binding region, based
      on the crystal structure of Deinococcus radiodurans phytochrome, we predict that
      three of the four Class II mutated phyB residues are solvent exposed in a cleft
      between the presumptive PAS and GAF domains. This deduction suggests that these
      residues could be directly required for the physical interaction of phyB with
      PIF3. Because these three residues are also necessary for phyB-imposed inhibition
      of hypocotyl elongation in response to red light, they are functionally necessary
      for signal transfer from photoactivated phyB, not only to PIF3 and other related
      bHLH transcription factors tested here, but also to other downstream signaling
      components involved in regulating seedling deetiolation.

PMID- 19165331
TI  - The IpaC carboxyterminal effector domain mediates Src-dependent actin
      polymerization during Shigella invasion of epithelial cells.
AB  - Shigella, the causative agent of bacillary dysentery, invades epithelial cells by
      locally reorganizing the actin cytoskeleton. Shigella invasion requires actin
      polymerization dependent on the Src tyrosine kinase and a functional bacterial
      type III secretion (T3S) apparatus. Using dynamic as well as immunofluorescence
      microscopy, we show that the T3S translocon component IpaC allows the recruitment
      of the Src kinase required for actin polymerization at bacterial entry sites
      during the initial stages of Shigella entry. Src recruitment occurred at
      bacterial-cell contact sites independent of actin polymerization at the onset of
      the invasive process and was still observed in Shigella strains mutated for
      translocated T3S effectors of invasion. A Shigella strain with a polar mutation
      that expressed low levels of the translocator components IpaB and IpaC was fully
      proficient for Src recruitment and bacterial invasion. In contrast, a Shigella
      strain mutated in the IpaC carboxyterminal effector domain that was proficient
      for T3S effector translocation did not induce Src recruitment. Consistent with a
      direct role for IpaC in Src activation, cell incubation with the IpaC last 72
      carboxyterminal residues fused to the Iota toxin Ia (IaC) component that
      translocates into the cell cytosol upon binding to the Ib component led to Src
      dependent ruffle formation. Strikingly, IaC also induced actin structures
      resembling bacterial entry foci that were enriched in activated Src and were
      inhibited by the Src inhibitor PP2. These results indicate that the IpaC effector
      domain determines Src-dependent actin polymerization and ruffle formation during
      bacterial invasion.

PMID- 19165332
TI  - A systematic approach to mapping recessive disease genes in individuals from
      outbred populations.
AB  - The identification of recessive disease-causing genes by homozygosity mapping is
      often restricted by lack of suitable consanguineous families. To overcome these
      limitations, we apply homozygosity mapping to single affected individuals from
      outbred populations. In 72 individuals of 54 kindred ascertained worldwide with
      known homozygous mutations in 13 different recessive disease genes, we performed
      total genome homozygosity mapping using 250,000 SNP arrays. Likelihood ratio Z
      scores (ZLR) were plotted across the genome to detect ZLR peaks that reflect
      segments of homozygosity by descent, which may harbor the mutated gene. In 93% of
      cases, the causative gene was positioned within a consistent ZLR peak of
      homozygosity. The number of peaks reflected the degree of inbreeding. We
      demonstrate that disease-causing homozygous mutations can be detected in single
      cases from outbred populations within a single ZLR peak of homozygosity as short
      as 2 Mb, containing an average of only 16 candidate genes. As many specialty
      clinics have access to cohorts of individuals from outbred populations, and as
      our approach will result in smaller genetic candidate regions, the new strategy
      of homozygosity mapping in single outbred individuals will strongly accelerate
      the discovery of novel recessive disease genes.

PMID- 19165333
TI  - Rab11A-controlled assembly of the inner membrane complex is required for
      completion of apicomplexan cytokinesis.
AB  - The final step during cell division is the separation of daughter cells, a
      process that requires the coordinated delivery and assembly of new membrane to
      the cleavage furrow. While most eukaryotic cells replicate by binary fission,
      replication of apicomplexan parasites involves the assembly of daughters
      (merozoites/tachyzoites) within the mother cell, using the so-called Inner
      Membrane Complex (IMC) as a scaffold. After de novo synthesis of the IMC and
      biogenesis or segregation of new organelles, daughters bud out of the mother cell
      to invade new host cells. Here, we demonstrate that the final step in parasite
      cell division involves delivery of new plasma membrane to the daughter cells, in
      a process requiring functional Rab11A. Importantly, Rab11A can be found in
      association with Myosin-Tail-Interacting-Protein (MTIP), also known as Myosin
      Light Chain 1 (MLC1), a member of a 4-protein motor complex called the glideosome
      that is known to be crucial for parasite invasion of host cells. Ablation of
      Rab11A function results in daughter parasites having an incompletely formed IMC
      that leads to a block at a late stage of cell division. A similar defect is
      observed upon inducible expression of a myosin A tail-only mutant. We propose a
      model where Rab11A-mediated vesicular traffic driven by an MTIP-Myosin motor is
      necessary for IMC maturation and to deliver new plasma membrane to daughter cells
      in order to complete cell division.

PMID- 19165334
TI  - Glial cell lineage expression of mutant ataxin-1 and huntingtin induces
      developmental and late-onset neuronal pathologies in Drosophila models.
AB  - BACKGROUND: In several neurodegenerative disorders, toxic effects of glial cells
      on neurons are implicated. However the generality of the non-cell autonomous
      pathologies derived from glial cells has not been established, and the
      specificity among different neurodegenerative disorders remains unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: We newly generated Drosophila models expressing
      human mutant huntingtin (hHtt103Q) or ataxin-1 (hAtx1-82Q) in the glial cell
      lineage at different stages of differentiation, and analyzed their morphological
      and behavioral phenotypes. To express hHtt103Q and hAtx1-82Q, we used 2 different
      Gal4 drivers, gcm-Gal4 and repo-Gal4. Gcm-Gal4 is known to be a
      neuroglioblast/glioblast-specific driver whose effect is limited to development.
      Repo-Gal4 is known to be a pan-glial driver and the expression starts at
      glioblasts and continues after terminal differentiation. Gcm-Gal4-induced
      hHtt103Q was more toxic than repo-Gal4-induced hHtt103Q from the aspects of
      development, locomotive activity and survival of flies. When hAtx1-82Q was
      expressed by gcm- or repo-Gal4 driver, no fly became adult. Interestingly, the
      head and brain sizes were markedly reduced in a part of pupae expressing hAtx1
      82Q under the control of gcm-Gal4, and these pupae showed extreme destruction of
      the brain structure. The other pupae expressing hAtx1-82Q also showed brain
      shrinkage and abnormal connections of neurons. These results suggested that
      expression of polyQ proteins in neuroglioblasts provided a remarkable effect on
      the developmental and adult brains, and that glial cell lineage expression of
      hAtx1-82Q was more toxic than that of hHtt103Q in our assays.
      CONCLUSION/SIGNIFICANCE: All these studies suggested that the non-cell autonomous
      effect of glial cells might be a common pathology shared by multiple
      neurodegenerative disorders. In addition, the fly models would be available for
      analyzing molecular pathologies and developing novel therapeutics against the non
      cell autonomous polyQ pathology. In conclusion, our novel fly models have
      extended the non-cell autonomous pathology hypothesis as well as the
      developmental effect hypothesis to multiple polyQ diseases. The two pathologies
      might be generally shared in neurodegeneration.

PMID- 19165335
TI  - BOLD correlates of trial-by-trial reaction time variability in gray and white
      matter: a multi-study fMRI analysis.
AB  - BACKGROUND: Reaction time (RT) is one of the most widely used measures of
      performance in experimental psychology, yet relatively few fMRI studies have
      included trial-by-trial differences in RT as a predictor variable in their
      analyses. Using a multi-study approach, we investigated whether there are brain
      regions that show a general relationship between trial-by-trial RT variability
      and activation across a range of cognitive tasks. METHODOLOGY/PRINCIPAL FINDINGS:
      The relation between trial-by-trial differences in RT and brain activation was
      modeled in five different fMRI datasets spanning a range of experimental tasks
      and stimulus modalities. Three main findings were identified. First, in a widely
      distributed set of gray and white matter regions, activation was delayed on
      trials with long RTs relative to short RTs, suggesting delayed initiation of
      underlying physiological processes. Second, in lateral and medial frontal
      regions, activation showed a "time-on-task" effect, increasing linearly as a
      function of RT. Finally, RT variability reliably modulated the BOLD signal not
      only in gray matter but also in diffuse regions of white matter.
      CONCLUSIONS/SIGNIFICANCE: The results highlight the importance of modeling trial
      by-trial RT in fMRI analyses and raise the possibility that RT variability may
      provide a powerful probe for investigating the previously elusive white matter
      BOLD signal.

PMID- 19165336
TI  - Multiple chromosomal rearrangements structured the ancestral vertebrate Hox
      bearing protochromosomes.
AB  - While the proposal that large-scale genome expansions occurred early in
      vertebrate evolution is widely accepted, the exact mechanisms of the expansion-
      such as a single or multiple rounds of whole genome duplication, bloc chromosome
      duplications, large-scale individual gene duplications, or some combination of
      these--is unclear. Gene families with a single invertebrate member but four
      vertebrate members, such as the Hox clusters, provided early support for Ohno's
      hypothesis that two rounds of genome duplication (the 2R-model) occurred in the
      stem lineage of extant vertebrates. However, despite extensive study, the
      duplication history of the Hox clusters has remained unclear, calling into
      question its usefulness in resolving the role of large-scale gene or genome
      duplications in early vertebrates. Here, we present a phylogenetic analysis of
      the vertebrate Hox clusters and several linked genes (the Hox "paralogon") and
      show that different phylogenies are obtained for Dlx and Col genes than for Hox
      and ErbB genes. We show that these results are robust to errors in phylogenetic
      inference and suggest that these competing phylogenies can be resolved if two
      chromosomal crossover events occurred in the ancestral vertebrate. These results
      resolve conflicting data on the order of Hox gene duplications and the role of
      genome duplication in vertebrate evolution and suggest that a period of genome
      reorganization occurred after genome duplications in early vertebrates.

PMID- 19165337
TI  - Trypanosome lytic factor, an antimicrobial high-density lipoprotein, ameliorates
      Leishmania infection.
AB  - Innate immunity is the first line of defense against invading microorganisms.
      Trypanosome Lytic Factor (TLF) is a minor sub-fraction of human high-density
      lipoprotein that provides innate immunity by completely protecting humans from
      infection by most species of African trypanosomes, which belong to the
      Kinetoplastida order. Herein, we demonstrate the broader protective effects of
      human TLF, which inhibits intracellular infection by Leishmania, a kinetoplastid
      that replicates in phagolysosomes of macrophages. We show that TLF accumulates
      within the parasitophorous vacuole of macrophages in vitro and reduces the number
      of Leishmania metacyclic promastigotes, but not amastigotes. We do not detect any
      activation of the macrophages by TLF in the presence or absence of Leishmania,
      and therefore propose that TLF directly damages the parasite in the acidic
      parasitophorous vacuole. To investigate the physiological relevance of this
      observation, we have reconstituted lytic activity in vivo by generating mice that
      express the two main protein components of TLFs: human apolipoprotein L-I and
      haptoglobin-related protein. Both proteins are expressed in mice at levels
      equivalent to those found in humans and circulate within high-density
      lipoproteins. We find that TLF mice can ameliorate an infection with Leishmania
      by significantly reducing the pathogen burden. In contrast, TLF mice were not
      protected against infection by the kinetoplastid Trypanosoma cruzi, which infects
      many cell types and transiently passes through a phagolysosome. We conclude that
      TLF not only determines species specificity for African trypanosomes, but can
      also ameliorate an infection with Leishmania, while having no effect on T. cruzi.
      We propose that TLFs are a component of the innate immune system that can limit
      infections by their ability to selectively damage pathogens in phagolysosomes
      within the reticuloendothelial system.

PMID- 19165338
TI  - Viral mimicry of Cdc2/cyclin-dependent kinase 1 mediates disruption of nuclear
      lamina during human cytomegalovirus nuclear egress.
AB  - The nuclear lamina is a major obstacle encountered by herpesvirus nucleocapsids
      in their passage from the nucleus to the cytoplasm (nuclear egress). We found
      that the human cytomegalovirus (HCMV)-encoded protein kinase UL97, which is
      required for efficient nuclear egress, phosphorylates the nuclear lamina
      component lamin A/C in vitro on sites targeted by Cdc2/cyclin-dependent kinase 1,
      the enzyme that is responsible for breaking down the nuclear lamina during
      mitosis. Quantitative mass spectrometry analyses, comparing lamin A/C isolated
      from cells infected with viruses either expressing or lacking UL97 activity,
      revealed UL97-dependent phosphorylation of lamin A/C on the serine at residue 22
      (Ser(22)). Transient treatment of HCMV-infected cells with maribavir, an
      inhibitor of UL97 kinase activity, reduced lamin A/C phosphorylation by
      approximately 50%, consistent with UL97 directly phosphorylating lamin A/C during
      HCMV replication. Phosphorylation of lamin A/C during viral replication was
      accompanied by changes in the shape of the nucleus, as well as thinning,
      invaginations, and discrete breaks in the nuclear lamina, all of which required
      UL97 activity. As Ser(22) is a phosphorylation site of particularly strong
      relevance for lamin A/C disassembly, our data support a model wherein viral
      mimicry of a mitotic host cell kinase activity promotes nuclear egress while
      accommodating viral arrest of the cell cycle.

PMID- 19165339
TI  - Interplay of Mre11 nuclease with Dna2 plus Sgs1 in Rad51-dependent
      recombinational repair.
AB  - The Mre11/Rad50/Xrs2 complex initiates IR repair by binding to the end of a
      double-strand break, resulting in 5' to 3' exonuclease degradation creating a
      single-stranded 3' overhang competent for strand invasion into the unbroken
      chromosome. The nuclease(s) involved are not well understood. Mre11 encodes a
      nuclease, but it has 3' to 5', rather than 5' to 3' activity. Furthermore,
      mutations that inactivate only the nuclease activity of Mre11 but not its other
      repair functions, mre11-D56N and mre11-H125N, are resistant to IR. This suggests
      that another nuclease can catalyze 5' to 3' degradation. One candidate nuclease
      that has not been tested to date because it is encoded by an essential gene is
      the Dna2 helicase/nuclease. We recently reported the ability to suppress the
      lethality of a dna2Delta with a pif1Delta. The dna2Delta pif1Delta mutant is IR
      resistant. We have determined that dna2Delta pif1Delta mre11-D56N and dna2Delta
      pif1Delta mre11-H125N strains are equally as sensitive to IR as mre11Delta
      strains, suggesting that in the absence of Dna2, Mre11 nuclease carries out
      repair. The dna2Delta pif1Delta mre11-D56N triple mutant is complemented by
      plasmids expressing Mre11, Dna2 or dna2K1080E, a mutant with defective helicase
      and functional nuclease, demonstrating that the nuclease of Dna2 compensates for
      the absence of Mre11 nuclease in IR repair, presumably in 5' to 3' degradation at
      DSB ends. We further show that sgs1Delta mre11-H125N, but not sgs1Delta, is very
      sensitive to IR, implicating the Sgs1 helicase in the Dna2-mediated pathway.

PMID- 19165340
TI  - Lkb1 deficiency alters goblet and paneth cell differentiation in the small
      intestine.
AB  - The Lkb1 tumour suppressor is a multitasking kinase participating in a range of
      physiological processes. We have determined the impact of Lkb1 deficiency on
      intestinal homeostasis, particularly focussing on secretory cell differentiation
      and development since we observe strong expression of Lkb1 in normal small
      intestine Paneth and goblet cells. We crossed mice bearing an Lkb1 allele flanked
      with LoxP sites with those carrying a Cyp1a1-specific inducible Cre recombinase.
      Lkb1 was efficiently deleted from the epithelial cells of the mouse intestine
      after intraperitoneal injection of the inducing agent beta-naphthoflavone. Bi
      allelic loss of Lkb1 led to the perturbed development of Paneth and goblet cell
      lineages. These changes were characterised by the lack of Delta ligand expression
      in Lkb1-deficient secretory cells and a significant increase in the levels of the
      downstream Notch signalling effector Hes5 but not Hes1. Our data show that Lkb1
      is required for the normal differentiation of secretory cell lineages within the
      intestine, and that Lkb1 deficiency modulates Notch signalling modulation in post
      mitotic cells.

PMID- 19165341
TI  - Nuclear envelope remnants: fluid membranes enriched in sterols and
      polyphosphoinositides.
AB  - BACKGROUND: The cytoplasm of eukaryotic cells is a highly dynamic compartment
      where membranes readily undergo fission and fusion to reorganize the cytoplasmic
      architecture, and to import, export and transport various cargos within the cell.
      The double membrane of the nuclear envelope that surrounds the nucleus,
      segregates the chromosomes from cytoplasm and regulates nucleocytoplasmic
      transport through pores. Many details of its formation are still unclear. At
      fertilization the sperm devoid of nuclear envelope pores enters the egg. Although
      most of the sperm nuclear envelope disassembles, remnants of the envelope at the
      acrosomal and centriolar fossae do not and are subsequently incorporated into the
      newly forming male pronuclear envelope. Remnants are conserved from annelid to
      mammalian sperm. METHODOLOGY/PRINCIPAL FINDINGS: Using lipid mass spectrometry
      and a new application of deuterium solid-state NMR spectroscopy we have
      characterized the lipid composition and membrane dynamics of the sperm nuclear
      envelope remnants in isolated sperm nuclei. CONCLUSIONS/SIGNIFICANCE: We report
      nuclear envelope remnants are relatively fluid membranes rich in sterols, devoid
      of sphingomyelin, and highly enriched in polyphosphoinositides and
      polyunsaturated phospholipids. The localization of the polybasic effector domain
      of MARCKS illustrates the non-nuclear aspect of the polyphosphoinositides. Based
      on their atypical biophysical characteristics and phospholipid composition, we
      suggest a possible role for nuclear envelope remnants in membrane fusion leading
      to nuclear envelope assembly.

PMID- 19165342
TI  - In vitro priming recapitulates in vivo HIV-1 specific T cell responses, revealing
      rapid loss of virus reactive CD4 T cells in acute HIV-1 infection.
AB  - BACKGROUND: The requirements for priming of HIV-specific T cell responses
      initially seen in infected individuals remain to be defined. Activation of T cell
      responses in lymph nodes requires cell-cell contact between T cells and DCs,
      which can give concurrent activation of T cells and HIV transmission.
      METHODOLOGY: The study aim was to establish whether DCs pulsed with HIV-1 could
      prime HIV-specific T cell responses and to characterize these responses. Both
      infectious and aldrithiol-2 inactivated noninfectious HIV-1 were compared to
      establish efficiencies in priming and the type of responses elicited. FINDINGS:
      Our findings show that both infectious and inactivated HIV-1 pulsed DCs can prime
      HIV-specific responses from naive T cells. Responses included several CD4(+) and
      CD8(+) T cell epitopes shown to be recognized in vivo by acutely and chronically
      infected individuals and some CD4(+) T cell epitopes not identified previously.
      Follow up studies of acute and recent HIV infected samples revealed that these
      latter epitopes are among the earliest recognized in vivo, but the responses are
      lost rapidly, presumably through activation-induced general CD4(+) T cell
      depletion which renders the newly activated HIV-specific CD4(+) T cells prime
      targets for elimination. CONCLUSION: Our studies highlight the ability of DCs to
      efficiently prime naive T cells and induce a broad repertoire of HIV-specific
      responses and also provide valuable insights to the pathogenesis of HIV-1
      infection in vivo.

PMID- 19165343
TI  - Interaction of the deubiquitinating enzyme Ubp2 and the e3 ligase Rsp5 is
      required for transporter/receptor sorting in the multivesicular body pathway.
AB  - Protein ubiquitination is essential for many events linked to intracellular
      protein trafficking. We sought to elucidate the possible involvement of the S.
      cerevisiae deubiquitinating enzyme Ubp2 in transporter and receptor trafficking
      after we (this study) and others established that affinity purified Ubp2
      interacts stably with the E3 ubiquitin ligase Rsp5 and the (ubiquitin associated)
      UBA domain containing protein Rup1. UBP2 interacts genetically with RSP5, while
      Rup1 facilitates the tethering of Ubp2 to Rsp5 via a PPPSY motif. Using the
      uracil permease Fur4 as a model reporter system, we establish a role for Ubp2 in
      membrane protein turnover. Similar to hypomorphic rsp5 alleles, cells deleted for
      UBP2 exhibited a temporal stabilization of Fur4 at the plasma membrane,
      indicative of perturbed protein trafficking. This defect was ubiquitin dependent,
      as a Fur4 N-terminal ubiquitin fusion construct bypassed the block and restored
      sorting in the mutant. Moreover, the defect was absent in conditions where
      recycling was absent, implicating Ubp2 in sorting at the multivesicular body.
      Taken together, our data suggest a previously overlooked role for Ubp2 as a
      positive regulator of Rsp5-mediated membrane protein trafficking subsequent to
      endocytosis.

PMID- 19165344
TI  - Integrating computational biology and forward genetics in Drosophila.
AB  - Genetic screens are powerful methods for the discovery of gene-phenotype
      associations. However, a systems biology approach to genetics must leverage the
      massive amount of "omics" data to enhance the power and speed of functional gene
      discovery in vivo. Thus far, few computational methods for gene function
      prediction have been rigorously tested for their performance on a genome-wide
      scale in vivo. In this work, we demonstrate that integrating genome-wide
      computational gene prioritization with large-scale genetic screening is a
      powerful tool for functional gene discovery. To discover genes involved in neural
      development in Drosophila, we extend our strategy for the prioritization of human
      candidate disease genes to functional prioritization in Drosophila. We then
      integrate this prioritization strategy with a large-scale genetic screen for
      interactors of the proneural transcription factor Atonal using genomic
      deficiencies and mutant and RNAi collections. Using the prioritized genes
      validated in our genetic screen, we describe a novel genetic interaction network
      for Atonal. Lastly, we prioritize the whole Drosophila genome and identify
      candidate gene associations for ten receptor-signaling pathways. This novel
      database of prioritized pathway candidates, as well as a web application for
      functional prioritization in Drosophila, called Endeavour-HighFly, and the Atonal
      network, are publicly available resources. A systems genetics approach that
      combines the power of computational predictions with in vivo genetic screens
      strongly enhances the process of gene function and gene-gene association
      discovery.

PMID- 19165345
TI  - Islet specific Wnt activation in human type II diabetes.
AB  - The Wnt pathway effector gene TCF7L2 has been linked to type II diabetes, making
      it important to study the role of Wnt signaling in diabetes pathogenesis. We
      examined the expression of multiple Wnt pathway components in pancreases from
      normal individuals and type II diabetic individuals. Multiple members of the Wnt
      signaling pathway, including TCF7L2, Wnt2b, beta-catenin, pGSK3beta, TCF3,
      cyclinD1, and c-myc, were undetectable or expressed at low levels in islets from
      nondiabetic individuals, but were also upregulated specifically in islets of type
      II diabetic patients. Culture of pancreatic tissue and islet isolation led to Wnt
      activation that was reversed by the Wnt antagonist sFRP, demonstrating that Wnt
      activation in that setting was due to soluble Wnt factors. These data support a
      model in which the Wnt pathway plays a dynamic role in the pathogenesis of type
      II diabetes and suggest manipulation of Wnt signaling as a new approach to beta
      cell-directed diabetes therapy.

PMID- 19165346
TI  - M-CSF and GM-CSF regulation of STAT5 activation and DNA binding in myeloid cell
      differentiation is disrupted in nonobese diabetic mice.
AB  - Defects in macrophage colony-stimulating factor (M-CSF) signaling disrupt myeloid
      cell differentiation in nonobese diabetic (NOD) mice, blocking myeloid maturation
      into tolerogenic antigen-presenting cells (APCs). In the absence of M-CSF
      signaling, NOD myeloid cells have abnormally high granulocyte macrophage colony
      stimulating factor (GM-CSF) expression, and as a result, persistent activation of
      signal transducer/activator of transcription 5 (STAT5). Persistent STAT5
      phosphorylation found in NOD macrophages is not affected by inhibiting GM-CSF.
      However, STAT5 phosphorylation in NOD bone marrow cells is diminished if GM-CSF
      signaling is blocked. Moreover, if M-CSF signaling is inhibited, GM-CSF
      stimulation in vitro can promote STAT5 phosphorylation in nonautoimmune C57BL/6
      mouse bone marrow cultures to levels seen in the NOD. These findings suggest that
      excessive GM-CSF production in the NOD bone marrow may interfere with the
      temporal sequence of GM-CSF and M-CSF signaling needed to mediate normal STAT5
      function in myeloid cell differentiation gene regulation.

PMID- 19165347
TI  - Small renal masses: incidental diagnosis, clinical symptoms, and prognostic
      factors.
AB  - Introduction. The small renal masses (SRMs) have increased over the past two
      decades due to more liberal use of imaging techniques. SRMs have allowed
      discussions regarding their prognostic, diagnosis, and therapeutic approach.
      Materials and methods. Clinical presentation, incidental diagnosis, and prognosis
      factors of SRMs are discussed in this review. Results. SRMs are defined as
      lesions less than 4 cm in diameter. SRM could be benign, and most malignant SMRs
      are low stage and low grade. Clinical symptoms like hematuria are very rare,
      being diagnosed by chance (incidental) in most cases. Size, stage, and grade are
      still the most consistent prognosis factors in (RCC). An enhanced contrast SRM
      that grows during active surveillance is clearly malignant, and its aggressive
      potential increases in those greater than 3 cm. Clear cell carcinoma is the most
      frequent cellular type of malign SRM. Conclusions. Only some SRMs are benign. The
      great majority of malign SRMs have good prognosis (low stage and grade, no
      metastasis) with open or laparoscopic surgical treatment (nephron sparing
      techniques). Active surveillance is an accepted attitude in selected cases.

PMID- 19165348
TI  - Recovery High Schools: A Descriptive Study of School Programs and Students.
AB  - High schools specifically designed for students recovering from a substance use
      disorder (substance abuse or dependence) have been emerging as a continuing care
      resource since 1987. This study of 17 schools provides the first systematic
      description of recovery school programs and their students. The most common
      school model is that of a program or affiliated school, embedded organizationally
      and physically with another school or set of alternative school programs.
      Although embedded, there are serious efforts to maintain physical separation of
      recovery school students from other students, using scheduling and physical
      barriers. Affiliation with public school systems is the case for most recovery
      schools, and seems to be a major factor in assuring fiscal and organizational
      feasibility.The students in the recovery high schools studied were predominantly
      white (78%), with about one-half from two parent homes. Overall parent
      educational levels suggest a higher mean SES than in the general population. Most
      students (78%) had prior formal treatment for substance use disorders, often
      concomitantly with treatment for mental health concerns, and were often referred
      by treatment providers. Students came with a broad and complex range of mental
      health issues, traumatic experiences, drug use patterns, criminal justice
      involvement, and educational backgrounds. The complexity of these problems
      clearly limits the enrollment capacity of the schools.Retrospective pretest to
      post-test analysis suggests significant reduction in substance use as well as in
      mental health symptoms among the students. Students were very positive in their
      assessment of the therapeutic value of the schools, but less enthusiastic
      regarding the educational programs. The school programs appear to successfully
      function as continuing care to reinforce and sustain the therapeutic benefits
      students gained from their treatment experiences.

PMID- 19165349
TI  - Educational differences in all-cause mortality by marital status - Evidence from
      Bulgaria, Finland and the United States.
AB  - Using life table measures, we compare educational differentials in all-cause
      mortality at ages 40 to 70 in Bulgaria to those in Finland and the United States.
      Specifically, we assess whether the relationship between education and mortality
      is modified by marital status. Although high education and being married are
      associated with lower mortality in all three countries, absolute educational
      differences tend to be smaller among married than unmarried individuals. Absolute
      differentials by education are largest for Bulgarian men, but in relative terms
      educational differences are smaller among Bulgarian men than in Finland and the
      U.S. Among women, Americans experience the largest education-mortality gradients
      in both relative and absolute terms. Our results indicate a particular need to
      tackle health hazards among poorly educated men in countries in transition.

PMID- 19165350
TI  - TFIP11 interacts with mDEAH9, an RNA helicase involved in spliceosome
      disassembly.
AB  - Yeast proteins Ntr1, Ntr2 and Prp43 function in spliceosome disassembly. An Ntr1
      Ntr2 protein complex recruits Prp43 to allow the removal of the lariat-intron in
      late-stage RNA splicing activity. Based on amino-acid sequence similarities
      across species, TFIP11 and mDEAH9/Dhx15 have been identified as homologues of
      yeast Ntr1 and Prp43, respectively. The N-terminal region of TFIP11 contains a G
      patch, which is a highly conserved domain of many RNA-processing proteins. TFIP11
      displays a unique and characteristic subnuclear localization pattern, in close
      proximity to SC35 nuclear speckles. Transfected GFP-tagged mDEAH9 displays an
      evenly distributed nuclear localization and is excluded from the nucleoli;
      however when TFIP11 and mDEAH9 are co-transfected, both proteins colocalize to
      distinct nuclear speckles. These data show that TFIP11 recruits mDEAH9 suggesting
      that these two proteins have similar biological activities to their yeast
      counterparts.

PMID- 19165351
TI  - Terminal Continuation (TC) RNA amplification enables expression profiling using
      minute RNA input obtained from mouse brain.
AB  - A novel methodology named terminal continuation (TC) RNA amplification has been
      developed to amplify RNA from minute amounts of starting material. Utility of the
      TC RNA amplification method is demonstrated with two new modifications including
      obviating the need for second strand synthesis, and purifying the amplification
      template using column filtration prior to in vitro transcription (IVT). Using
      four low concentrations of RNA extracted from mouse brain (1, 10, 25 and 50 ng),
      one round TC RNA amplification was compared to one round amplified antisense RNA
      (aRNA) in conjunction with column filtration and drop dialysis purification. The
      TC RNA amplification without second strand synthesis performed extremely well on
      custom-designed cDNA array platforms, and column filtration was found to provide
      higher positive detection of individual clones when hybridization signal
      intensity was subtracted from corresponding negative control hybridization signal
      levels. Results indicate that TC RNA amplification without second strand
      synthesis, in conjunction with column filtration, is an excellent method for RNA
      amplification from extremely small amounts of input RNA from mouse brain and
      postmortem human brain, and is compatible with microaspiration strategies and
      subsequent microarray analysis.

PMID- 19165352
TI  - Unobtrusive In-Home Monitoring of Cognitive and Physical Health: Reactions and
      Perceptions of Older Adults.
AB  - While the potential benefits of unobtrusive in-home sensing technologies for
      maintaining health and independence of older adults have been highlighted in
      recent research, little is known about their views toward such technology. The
      aims of this project were to identify monitoring needs and expectations of
      community-residing elderly and their family members. Focus groups were presented
      with examples of in-home monitoring devices and data output; participants were
      asked to consider whether the data showed information that was meaningful to
      them, and how and to whom they would like to have such data disseminated. Content
      analysis of transcripts revealed four dominant themes: maintaining independence,
      detecting cognitive decline, sharing of information, and the tradeoff between
      privacy and usefulness of monitoring. The acceptance by elderly of unobtrusive in
      home monitoring was closely tied to perceived utility of data generated by such
      systems. Privacy concerns appeared to be less of an issue than anticipated in
      this sample.

PMID- 19165353
TI  - N-terminal pro-brain natriuretic peptide and atrial fibrillation.
AB  - NT-proBNP is produced from both atria and ventricles. The primary regulation of
      production is at the synthesis level. The plasma half-life of NT-proBNP is 60-120
      min. Cutoff value of NT-proBNP for diagnosis of heart failure is 125 pg/ml in the
      age group below 75 years and 450 pg/ml in the age group above 75 years. It
      increases in atrial fibrillation and drops after successful cardioversion. High
      levels predict development of atrial fibrillation (AF) in healthy persons with
      sinus rhythm (SR). Some studies concluded that baseline level predicts
      maintenance of SR after cardioversion of AF while some others found that it did
      not. Many studies have proven that it is useful in monitoring rhythm stability
      after cardioversion of AF. Since it is increased in many other conditions, out of
      which some may also cause AF, care must be taken before ascribing changes in its
      level to AF alone.

PMID- 19165354
TI  - Clinical picture of arrhythmogenic right ventricular dysplasia / cardiomyopathy
      patients from Indian origin.
AB  - OBJECTIVE: Among the inherited cardiomyopathies, Arrhythmogenic right ventricular
      dysplasia/cardiomyopathy is unique with a peculiar pathology of fibro-fatty
      replacement. Studies have been carried out all over the world and several groups
      have reported clinical heterogeneity in manifestation of ARVD/C related symptoms.
      Present study is an attempt to identify the clinical profile of ARVD/C patients
      from Asian Indian origin. METHODS: 31 patients in the span of three years were
      diagnosed with ARVD/C. Diagnosis was based on proposed task force criteria.
      RESULTS: The mean age at diagnosis was 32.9 +/- 16.4 years with slight tilt in
      male to female ratio (1.46). About 80% cases had palpitations, syncope in 45.16%
      and dyspnea in 22.5%, whereas 16% of patients were asymptomatic. About 50% of
      patients revealed a family history of confirmed ARVD/C or sudden death of a
      family member without any known cause. ECG showed T-wave inversion in about 60%
      cases, prolongation of QRS was observed in 20% cases. RV dilatation was observed
      in 80% of patients and 66.7% showed systolic dysfunction. RV free wall motion
      abnormalities were found in 33% patients. Most of the early onset cases with less
      than 30 years of age showed family history indicative of ARVD/C. Familial study
      in three patients indicated early onset of condition in younger generations in
      two families. CONCLUSIONS: ARVD/C in India shows relatively early age at onset
      when compared with other Asian populations with more than half of patients
      showing the disease below the age of 30 years. History in most of the early onset
      cases revealed family history indicating strong genetic influence.

PMID- 19165355
TI  - Baseline NT-Pro-BNP levels and arrhythmia recurrence in outpatients undergoing
      elective cardioversion of persistent atrial fibrillation: a survival analysis.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia encountered in
      clinical practice. Elective electrical cardioversion is often performed in
      patients with persistent AF to attempt sinus rhythm (SR) restoration. However, AF
      recurrences are frequent after successful cardioversion and several predictors
      have been identified. AIM OF THE STUDY: The present study was designed to
      prospectively analyse the correlation between NT-pro-BNP levels and AF recurrence
      in consecutive patients referred for electrical cardioversion of persistent
      atrial fibrillation. RESULTS: Forty consecutive patients referred for elective
      cardioversion of AF were enrolled in the study. Cardioversion restored sinus
      rhythm in 34/40 patients but 2 of them presented an early recurrence of AF before
      discharge. Patients were then followed for 6 months to assess AF recurrence. Cox
      regression analysis was performed using the parameters found predictive on
      univariate survival analysis (NT-pro-BNP quartiles, beta-blockers). The only
      independent predictor of AF recurrence on Cox-regression analysis was a level of
      NT-pro-BNP in the fourth quartile (HR 3.21 95%CI 1.26-8.14, p=0.014). On receiver
      operating curve (ROC) analysis, NT-pro-BNP levels above 1707 pg/ml had a
      specificity of 92% (and a sensitivity of 36%) in predicting atrial fibrillation
      recurrence by 6 months. CONCLUSIONS: Baseline NT-pro-BNP levels are an
      independent predictor of AF recurrence at 6 months follow-up in candidates for
      elective direct current cardioversion.

PMID- 19165356
TI  - Ventricular dyssynchrony: 12-month evaluation in ischemic versus nonischemic CRT
      patients.
AB  - OBJECTIVE: Few data exist about the potential differences in the dyssynchrony
      status of cardiac resynchronization therapy (CRT) candidates stratified by
      etiology of heart failure, and about the evolution of dyssynchrony at long-term
      follow-up. We provided a description of intra-ventricular dyssynchrony at
      baseline, 6 months and 12 months in ischemic and nonischemic CRT patients.
      METHODS: Tissue Doppler Imaging was performed in 35 CRT candidates (18 ischemic,
      17 nonischemic) at baseline, and at 6-month and 12-month follow-up. A group of 11
      healthy subjects was considered for comparison. RESULTS: At baseline, the
      standard deviation and the maximum activation delay between any 2 segments were
      significantly greater in ischemic (38+/-33ms, 94+/-76ms) and nonischemic (38+/
      24ms, 96+/-62ms) patients versus controls (9+/-7ms, 22+/-15ms) (all p<0.05). The
      average time to activation for posterior and lateral wall was significantly
      higher in nonischemic patients, while the anterior septum activated later in
      ischemic patients. At 6-month follow-up, standard deviation and maximum delay did
      not vary in nonischemic while decreased in ischemic group. All changes persisted
      at 12 months. CONCLUSIONS: No baseline differences were observed between ischemic
      and nonischemic patients using studied indices. At 6- and 12-month follow-up,
      only ischemic patients presented a significant reduction in dyssynchrony values,
      although in both groups CRT did not lead to a complete normalization of LV
      synchronism.

PMID- 19165357
TI  - Effect of different doses of noradrenaline against ischemia-induced ventricular
      arrhythmias in rat heart in vivo.
AB  - BACKGROUND: The present study was designed to evaluate the preconditioning effect
      of different doses of noradrenaline on ischemia-induced ventricular arrhythmias
      in open chest anesthetized rats. METHODS: The anaesthetized rats were subjected
      to 25 min of regional ischemia by left descending coronary artery (LAD)
      occlusion. In sham group, surgical procedures were done but ischemia was not
      applied. In control rats, saline was injected prior to ischemia. In noradrenaline
      groups, rats pretreated with three different doses of noradrenaline
      (respectively, 0.5, 1 and 2 microg/kg, IV). RESULTS: In control rats, induction
      of ischemia shortened the QTc (corrected QT) interval (ms) and led to occurrence
      of ventricular arrhythmias. Administration of low-dose of noradrenaline prevented
      shortening of the QTc interval during ischemia but could not significantly
      attenuate severity and incidences of arrhythmias. Injection of mid-dose of
      noradrenaline stabilized the QTc during ischemia and reduced severity of
      arrhythmias. Pretreatment with high-dose of noradrenaline significantly prolonged
      the QTc interval and declined severity and incidence of arrhythmias. CONCLUSIONS:
      Noradrenaline dose-dependently attenuated ischemia-induced ventricular
      arrhythmias.

PMID- 19165358
TI  - Effect of L- arginine on electrocardiographic changes induced by
      hypercholesterolemia and isoproterenol in rabbits.
AB  - Hypercholesterolemia, a well-known cardiovascular risk factor, is associated with
      prolonged action potential duration, longer QTc intervals (rate controlled QT
      interval), suggested that Hypercholesterolemia may have a direct effect on
      ventricular repolarization. Hypercholesterolemia was induced in rabbits and L
      arginine was given orally to animals for sixteen weeks. The isoproterenol was
      injected in all the animals to produce electrocardiographic changes. ECG was
      recorded in lead II at start of study, after hypercholesterolemic diet and/ or L
      arginine supplementation. It is observed that L-arginine significantly reduced
      the hypercholesterolemia induced QTc prolongation. Isoproterenol induced increase
      in QTc intervals were decreased only in normolipidemic animals. No significant
      changes were observed in QRS complex and heart rate. Our study suggests that L
      arginine definitely have effect on repolarization processes of myocardium.

PMID- 19165359
TI  - Assessing heart rate variability using a 12 lead ECG in patients with alcohol
      dependence syndrome.
AB  - Heavy or hazardous drinking is associated with an increased risk of cardiac
      morbidity and mortality and this has been attributed to abnormalities in cardiac
      autonomic regulation. Current study aimed to assess the role of simple indices
      derived from 12 lead ECG in subjects with chronic alcohol dependence. Data
      suggested that alcohol group had significantly lower 12 lead ECG derived RR
      variability compared to age and gender matched controls. Study further supports
      the implication of 12 lead derived RR variability indices in various clinical
      settings.

PMID- 19165360
TI  - Brugada-type electrocardiographic pattern induced by electrocution.
AB  - Heart is one of the most frequently affected organs in electrocution. Electrical
      injury can cause life-threatening cardiac complications such as asystole,
      ventricular fibrillation, and myocardial rupture. In this case report, we
      describe a 22-yr-old male patient who sustained electric burn injury and
      presented with electrocardiogram showing transient Brugada type pattern.

PMID- 19165361
TI  - AV nodal reentrant tachycardia causing inappropriate ICD shocks in a patient with
      arrhythmogenic RV dysplasia.
AB  - We report a patient with an implantable cardioverter defibrillator (ICD) for
      arrhythmogenic right ventricular dysplasia (ARVD) who received inappropriate
      shocks for atrioventricular node reentry tachycardia (AVRNT). Patient had
      multiple shocks for tachycardia with EGM characteristics of very short VA
      interval and CL of 300 msec. An electrophysiologic (EP) study reproducibly
      induced typical AVNRT with similar features. The slow AV nodal pathway ablation
      resolved the ICD shocks. Despite increasingly sophisticated discrimination
      algorithms available in modern ICDs, the ability to differentiate SVT from VT can
      be challenging. Our patient received inappropriate shocks for AVNRT. When device
      interrogation alone is not conclusive, an EP study may be necessary to determine
      the appropriate therapeutic course.

PMID- 19165362
TI  - Termination of ventricular tachycardia with antitachycardia pacing after
      ineffective shock therapy in an ICD recipient with hypertrophic cardiomyopathy.
AB  - Implantable Cardioverter Defibrillator (ICD) implantation is the only established
      therapy for primary or secondary prevention of sudden cardiac death in patients
      with Hypertrophic Cardiomyopathy (HCM). Ineffectiveness of shock therapy for the
      termination of potentially fatal ventricular arrhythmias in ICD recipients is
      rare in the presence of appropriate arrhythmia detection by the device. We report
      the case of a 48-year-old woman with HCM and a single chamber ICD, who received
      five inefficient high-energy (35 Joules) shocks for the termination of an
      appropriately detected episode of Ventricular Tachycardia (VT). The episode was
      safely terminated with a subsequent application of Antitachycardia Pacing (ATP)
      by the device. At the following ICD control, an acceptable defibrillation
      threshold was detected.

PMID- 19165364
TI  - EHP Update.

PMID- 19165363
TI  - Inappropriate Shock delivered by Implantable Cardioverter Defibrillator--Cardiac
      Resynchronization Therapy (ICD-CRT) due to myopotential oversensing.
AB  - The clinical efficacy of ICD-CRT therapy depends on accurate sensing of
      intracardiac signals and sensing algorithms. We report the occurrence of sensing
      abnormality in a patient with ICD-CRT. In this patient, oversensing of
      myopotentials during strenuous muscular activity resulted in an inappropriate ICD
      CRT discharge. Although modern ICDs are highly effective in detecting and
      terminating malignant tachyarrhythmias, their detection specificity must be
      improved. It is possible to find the mechanism of arrhythmia by EGM. Simple
      device reprogramming make it possible to avoid the oversensing of myopotentials.

PMID- 19165365
TI  - A major milestone for the National Children's Study.

PMID- 19165367
TI  - Cord blood mercury and early child development: effects of the World Trade
      Center.

PMID- 19165369
TI  - Meeting report: summit focuses on pharmaceuticals in drinking water.

PMID- 19165373
TI  - Children's health: National Children's Study begins recruitment.

PMID- 19165374
TI  - Missing the dark: health effects of light pollution.

PMID- 19165375
TI  - Switch on the night: policies for smarter lighting.

PMID- 19165380
TI  - Is there evidence for synergy among air pollutants in causing health effects?
AB  - BACKGROUND: Environmental air pollutants are inhaled as complex mixtures, but the
      long dominant focus of monitoring and research on individual pollutants has
      provided modest insight into pollutant interactions that may be important to
      health. Trends toward managing multiple pollutants to maximize aggregate health
      gains place increasing value on knowing whether the effects of combinations of
      pollutants are greater than the sum of the effects of individual pollutants
      (synergy). OBJECTIVE: We reviewed selected published literature to determine
      whether synergistic effects of combinations of pollutants on health outcomes have
      actually been demonstrated. METHODS AND RESULTS: We reviewed 36 laboratory
      studies of combinations of ozone with other pollutants that were reported in the
      recent U.S. Environmental Protection Agency Ozone Criteria Document. We examined
      original reports to determine whether the experimental design tested for synergy
      and whether synergy was demonstrated. Fourteen studies demonstrated synergism,
      although synergistic, additive, and antagonistic effects were sometimes observed
      among different outcomes or at different times after exposure. CONCLUSIONS:
      Synergisms involving O3 have been demonstrated by laboratory studies of humans
      and animals. We conclude that the plausibility of synergisms among environmental
      pollutants has been established, although comparisons are limited, and most
      involved exposure concentrations much higher than typical of environmental
      pollutants. Epidemiologic research has limited ability to address the issue
      explicitly.

PMID- 19165381
TI  - Prenatal exposure to polychlorinated biphenyls: a neuropsychologic analysis.
AB  - OBJECTIVES: A large body of literature documents the effects of prenatal exposure
      to polychlorinated biphenyls (PCBs) on cognitive development of children. Despite
      this fact, no integrative synthesis has been published yet to identify the
      cognitive functions that are particularly affected. Our aim is to review this
      literature in an attempt to identify the cognitive profile associated with
      prenatal PCB exposure. DATA SOURCES: Studies were identified by searching the
      PubMed database for articles published before June 2008. We reviewed data from
      nine prospective longitudinal birth cohorts for different aspects of cognition.
      DATA EXTRACTION: Associations between indicators of prenatal PCB exposure and
      performance on cognitive tasks reported in the selected studies are summarized
      and classified as general cognitive abilities, verbal or visual-spatial skills,
      memory, attention, and executive functions. DATA SYNTHESIS: The most consistent
      effects observed across studies are impaired executive functioning related to
      increased prenatal PCB exposure. Negative effects on processing speed, verbal
      abilities, and visual recognition memory are also reported by most studies.
      Converging results from different cohort studies in which exposure arises from
      different sources make it unlikely that co-exposure with another associated
      contaminant is responsible for the observed effects. CONCLUSION: Prenatal PCB
      exposure appears to be related to a relatively specific cognitive profile of
      impairments. Failure to assess functions that are specifically impaired may
      explain the absence of effects found in some studies. Our findings have
      implications in the selection of cognitive assessment methods in future studies.

PMID- 19165382
TI  - A retrospective performance assessment of the developmental neurotoxicity study
      in support of OECD test guideline 426.
AB  - OBJECTIVE: We conducted a review of the history and performance of developmental
      neurotoxicity (DNT) testing in support of the finalization and implementation of
      Organisation of Economic Co-operation and Development (OECD) DNT test guideline
      426 (TG 426). INFORMATION SOURCES AND ANALYSIS: In this review we summarize
      extensive scientific efforts that form the foundation for this testing paradigm,
      including basic neurotoxicology research, interlaboratory collaborative studies,
      expert workshops, and validation studies, and we address the relevance,
      applicability, and use of the DNT study in risk assessment. CONCLUSIONS: The OECD
      DNT guideline represents the best available science for assessing the potential
      for DNT in human health risk assessment, and data generated with this protocol
      are relevant and reliable for the assessment of these end points. The test
      methods used have been subjected to an extensive history of international
      validation, peer review, and evaluation, which is contained in the public record.
      The reproducibility, reliability, and sensitivity of these methods have been
      demonstrated, using a wide variety of test substances, in accordance with OECD
      guidance on the validation and international acceptance of new or updated test
      methods for hazard characterization. Multiple independent, expert scientific peer
      reviews affirm these conclusions.

PMID- 19165383
TI  - Effect of calcium supplementation on blood lead levels in pregnancy: a randomized
      placebo-controlled trial.
AB  - BACKGROUND: Prenatal lead exposure is associated with deficits in fetal growth
      and neurodevelopment. Calcium supplementation may attenuate fetal exposure by
      inhibiting mobilization of maternal bone lead and/or intestinal absorption of
      ingested lead. OBJECTIVE: Our goal was to evaluate the effect of 1,200 mg dietary
      calcium supplementation on maternal blood lead levels during pregnancy. METHODS:
      In a double-blind, randomized, placebo-controlled trial conducted from 2001
      through 2003 in Mexico City, we randomly assigned 670 women in their first
      trimester of pregnancy to ingest calcium (n = 334) or placebo (n = 336). We
      followed subjects through pregnancy and evaluated the effect of supplementation
      on maternal blood lead, using an intent-to-treat analysis by a mixed-effects
      regression model with random intercept, in 557 participants (83%) who completed
      follow-up. We then conducted as-treated analyses using similar models stratified
      by treatment compliance. RESULTS: Adjusting for baseline lead level, age,
      trimester of pregnancy, and dietary energy and calcium intake, calcium was
      associated with an average 11% reduction (0.4 microg/dL) in blood lead level
      relative to placebo (p = 0.004). This reduction was more evident in the second
      trimester (-14%, p < 0.001) than in the third (-8%, p = 0.107) and was strongest
      in women who were most compliant (those who consumed > or = 75% calcium pills; 
      24%, p < 0.001), had baseline blood lead > 5 microg/dL (-17%, p < 0.01), or
      reported use of lead-glazed ceramics and high bone lead (-31%, p < 0.01).
      CONCLUSION: Calcium supplementation was associated with modest reductions in
      blood lead when administered during pregnancy and may constitute an important
      secondary prevention effort to reduce circulating maternal lead and,
      consequently, fetal exposure.

PMID- 19165384
TI  - Phthalates impair germ cell development in the human fetal testis in vitro
      without change in testosterone production.
AB  - BACKGROUND: Several studies have described an increasing frequency of male
      reproductive disorders, which may have a common origin in fetal life and which
      are hypothesized to be caused by endocrine disruptors. Phthalate esters represent
      a class of environmental endocrine-active chemicals known to disrupt development
      of the male reproductive tract by decreasing testosterone production in the fetal
      rat. OBJECTIVES: Using the organ culture system we developed previously, we
      investigated the effects on the development of human fetal testis of one
      phthalate--mono-2-ethylhexyl phthalate (MEHP)--an industrial chemical found in
      many products, which has been incriminated as a disruptor of male reproductive
      function. METHODS: Human fetal testes were recovered during the first trimester
      (7-12 weeks) of gestation, a critical period for testicular differentiation, and
      cultured for 3 days with or without MEHP in basal conditions or stimulated with
      luteinizing hormone (LH). RESULTS: Whatever the dose, MEHP treatment had no
      effect on basal or LH-stimulated testosterone produced by the human fetal testis
      in vitro, although testosterone production can be modulated in our culture
      system. MEHP (10(-4) M) did not affect proliferation or apoptosis of Sertoli
      cells, but it reduced the mRNA expression of anti-Mullerian hormone. MEHP (10(-4)
      M) reduced the number of germ cells by increasing their apoptosis, measured by
      the detection of caspase-3-positive germ cells, without modification of their
      proliferation. CONCLUSIONS: This is the first experimental demonstration that
      phthalates alter the development of the germ cell lineage in humans. However, in
      contrast to results observed in the rat, phthalates did not affect
      steroidogenesis.

PMID- 19165385
TI  - One-month diesel exhaust inhalation produces hypertensive gene expression pattern
      in healthy rats.
AB  - BACKGROUND: Exposure to diesel exhaust (DE) is linked to vasoconstriction,
      endothelial dysfunction, and myocardial ischemia in compromised individuals.
      OBJECTIVE: We hypothesized that DE inhalation would cause greater inflammation,
      hematologic alterations, and cardiac molecular impairment in spontaneously
      hypertensive (SH) rats than in healthy Wistar Kyoto (WKY) rats. METHODS AND
      RESULTS: Male rats (12-14 weeks of age) were exposed to air or DE from a 30-kW
      Deutz engine at 500 or 2,000 microg/m3, 4 hr/day, 5 days/week for 4 weeks.
      Neutrophilic influx was noted in the lung lavage fluid of both strains, but
      injury markers were minimally changed. Particle-laden macrophages were apparent
      histologically in DE-exposed rats. Lower baseline cardiac anti-oxidant enzyme
      activities were present in SH than in WKY rats; however, no DE effects were
      noted. Cardiac mitochondrial aconitase activity decreased after DE exposure in
      both strains. Electron microscopy indicated abnormalities in cardiac mitochondria
      of control SH but no DE effects. Gene expression profiling demonstrated
      alterations in 377 genes by DE in WKY but none in SH rats. The direction of DE
      induced changes in WKY mimicked expression pattern of control SH rats without DE.
      Most genes affected by DE were down-regulated in WKY. The same genes were down
      regulated in SH without DE producing a hypertensive-like expression pattern. The
      down-regulated genes included those that regulate compensatory response, matrix
      metabolism, mitochondrial function, and oxidative stress response. No up
      regulation of inflammatory genes was noted. CONCLUSIONS: We provide the evidence
      that DE inhalation produces a hypertensive-like cardiac gene expression pattern
      associated with mitochondrial oxidative stress in healthy rats.

PMID- 19165386
TI  - Adult women's blood mercury concentrations vary regionally in the United States:
      association with patterns of fish consumption (NHANES 1999-2004).
AB  - BACKGROUND: The current, continuous National Health and Nutrition Examination
      Survey (NHANES) has included blood mercury (BHg) and fish/shellfish consumption
      since it began in 1999. NHANES 1999-2004 data form the basis for these analyses.
      OBJECTIVES: This study was designed to determine BHg distributions within U.S.
      Census regions and within coastal and noncoastal areas among women of
      childbearing age, their association with patterns of fish consumption, and
      changes from 1999 through 2004. METHODS: We performed univariate and bivariate
      analyses to determine the distribution of BHg and fish consumption in the
      population and to investigate differences by geography, race/ethnicity, and
      income. We used multivariate analysis (regression) to determine the strongest
      predictors of BHg among geography, demographic factors, and fish consumption.
      RESULTS: Elevated BHg occurred more commonly among women of childbearing age
      living in coastal areas of the United States (approximately one in six women).
      Regionally, exposures differ across the United States: Northeast > South and West
      > Midwest. Asian women and women with higher income ate more fish and had higher
      BHg. Time-trend analyses identified reduced BHg and reduced intake of Hg in the
      upper percentiles without an overall reduction of fish consumption. CONCLUSIONS:
      BHg is associated with income, ethnicity, residence (census region and coastal
      proximity). From 1999 through 2004, BHg decreased without a concomitant decrease
      in fish consumption. Data are consistent with a shift over this time period in
      fish species in women's diets.

PMID- 19165387
TI  - Deducing in vivo toxicity of combustion-derived nanoparticles from a cell-free
      oxidative potency assay and metabolic activation of organic compounds.
AB  - BACKGROUND: The inhalation of combustion-derived nanoparticles (CDNPs) is
      believed to cause an oxidative stress response, which in turn may lead to
      pulmonary or even systemic inflammation. OBJECTIVE AND METHODS: In this study we
      assessed whether the in vivo inflammatory response--which is generally referred
      to as particle toxicity-of mice to CDNPs can be predicted in vitro by a cell-free
      ascorbate test for the surface reactivity or, more precisely, oxidative potency
      (OxPot) of particles. RESULTS: For six types of CDNPs with widely varying
      particle diameter (10-50 nm), organic content (OC; 1-20%), and specific Brunauer,
      Emmett, and Teller (BET) surface area (43-800 m2/g), OxPot correlated strongly
      with the in vivo inflammatory response (pulmonary polymorphonuclear neutrophil
      influx 24 hr after intratracheal particle instillation). However, for CDNPs with
      high organic content, OxPot could not explain the observed inflammatory response,
      possibly due to shielding of the OxPot of the carbon core of CDNPs by an organic
      coating. On the other hand, a pathway-specific gene expression screen indicated
      that, for particles rich in polycyclic aromatic hydrocarbon (PAHs), cytochrome
      P450 1A1 (CYP1A1) enzyme-mediated biotransformation of bio-available organics may
      generate oxidative stress and thus enhance the in vivo inflammatory response.
      CONCLUSION: The compensatory nature of both effects (shielding of carbon core and
      biotransformation of PAHs) results in a good correlation between inflammatory
      response and BET surface area for all CDNPs. Hence, the in vivo inflammatory
      response can either be predicted by BET surface area or by a simple quantitative
      model, based on in vitro OxPot and Cyp1a1 induction.

PMID- 19165388
TI  - The 2006 California heat wave: impacts on hospitalizations and emergency
      department visits.
AB  - BACKGROUND: Climate models project that heat waves will increase in frequency and
      severity. Despite many studies of mortality from heat waves, few studies have
      examined morbidity. OBJECTIVES: In this study we investigated whether any age or
      race/ethnicity groups experienced increased hospitalizations and emergency
      department (ED) visits overall or for selected illnesses during the 2006
      California heat wave. METHODS: We aggregated county-level hospitalizations and ED
      visits for all causes and for 10 cause groups into six geographic regions of
      California. We calculated excess morbidity and rate ratios (RRs) during the heat
      wave (15 July to 1 August 2006) and compared these data with those of a reference
      period (8-14 July and 12-22 August 2006). RESULTS: During the heat wave, 16,166
      excess ED visits and 1,182 excess hospitalizations occurred statewide. ED visits
      for heat-related causes increased across the state [RR = 6.30; 95% confidence
      interval (CI), 5.67-7.01], especially in the Central Coast region, which includes
      San Francisco. Children (0-4 years of age) and the elderly (> or = 65 years of
      age) were at greatest risk. ED visits also showed significant increases for acute
      renal failure, cardiovascular diseases, diabetes, electrolyte imbalance, and
      nephritis. We observed significantly elevated RRs for hospitalizations for heat
      related illnesses (RR = 10.15; 95% CI, 7.79-13.43), acute renal failure,
      electrolyte imbalance, and nephritis. CONCLUSIONS: The 2006 California heat wave
      had a substantial effect on morbidity, including regions with relatively modest
      temperatures. This suggests that population acclimatization and adaptive capacity
      influenced risk. By better understanding these impacts and population
      vulnerabilities, local communities can improve heat wave preparedness to cope
      with a globally warming future.

PMID- 19165389
TI  - DDT exposure of zebrafish embryos enhances seizure susceptibility: relationship
      to fetal p,p'-DDE burden and domoic acid exposure of California sea lions.
AB  - BACKGROUND: California sea lions have a large body burden of organochlorine
      pesticides, and over the last decade they have also been subject to domoic acid
      poisoning. Domoic acid poisoning, previously recognized in adult animals, is now
      viewed as a major cause of prenatal mortality. The appearance of a chronic
      juvenile domoic acid disease in the sea lions, characterized by behavioral
      abnormalities and epilepsy, is consistent with early life poisoning and may be
      potentiated by organochlorine burden. OBJECTIVE: We investigated the interactive
      effect of DDT (dichlorodiphenyltrichloroethane) on neurodevelopment using a
      zebrafish (Danio rerio) model for seizure behavior to examine the susceptibility
      to domoic acid-induced seizures after completion of neurodevelopment. METHODS:
      Embryos were exposed (6-30 hr postfertilization) to either o,p'-DDT or p,p'-DDE
      (dichlorodiphenyldichloroethylene) during neurodevelopment via a 0.1% dimethyl
      sulfoxide solution. These larval (7 days postfertilization) fish were then
      exposed to either the seizure-inducing drug pentylenetetrazol (PTZ) or domoic
      acid; resulting seizure behavior was monitored and analyzed for changes using
      cameras and behavioral tracking software. RESULTS: Embryonic exposure to DDTs
      enhanced PTZ seizures and caused distinct and increased seizure behaviors to
      domoic acid, most notably a type of head-shaking behavior. CONCLUSION: These
      studies demonstrate that embryonic exposure to DDTs leads to asymptomatic animals
      at completion of neurodevelopment with greater sensitivity to domoic acid-induced
      seizures. The body burden levels of p,p'-DDE are close to the range recently
      found in fetal California sea lions and suggest a potential interactive effect of
      p,p'-DDE embryonic poisoning and domoic acid toxicity.

PMID- 19165390
TI  - Urinary levoglucosan as a biomarker of wood smoke exposure: observations in a
      mouse model and in children.
AB  - BACKGROUND: Biomass smoke is an important source of particulate matter (PM), and
      much remains to be discovered with respect to the human health effects associated
      with this specific PM source. Exposure to biomass smoke can occur in one of two
      main categories: short-term exposures consist of periodic, seasonal exposures
      typified by communities near forest fires or intentional agricultural burning,
      and long-term exposures are chronic and typified by the use of biomass materials
      for cooking or heating. Levoglucosan (LG), a sugar anhydride released by
      combustion of cellulose-containing materials, is an attractive candidate as a
      biomarker of wood smoke exposure. OBJECTIVES: In the present study, Balb/c mice
      and children were assessed for LG in urine to determine its feasibility as a
      biomarker. METHODS: We performed urinary detection of LG by gas
      chromatography/mass spectrometry after intranasal instillations of LG or
      concentrated PM (mice) or biomass exposure (mice or humans). RESULTS: After
      instillation, we recovered most of the LG within the first 4 hr. Experiments
      using glucose instillation proved the specificity of our system, and instillation
      of concentrated PM from wood smoke, ambient air, and diesel exhaust supported a
      connection between wood smoke and LG. In addition, LG was detected in the urine
      of mice exposed to wood smoke. Finally, a pilot human study proved our ability to
      detect LG in urine of children. CONCLUSIONS: These results demonstrate that LG in
      the lungs is detectable in the urine of both mice and humans and that it is a
      good candidate as a biomarker of exposure to biomass smoke.

PMID- 19165391
TI  - Iron metabolism genes, low-level lead exposure, and QT interval.
AB  - BACKGROUND: Cumulative exposure to lead has been shown to be associated with
      depression of electrocardiographic conduction, such as QT interval (time from
      start of the Q wave to end of the T wave). Because iron can enhance the oxidative
      effects of lead, we examined whether polymorphisms in iron metabolism genes
      [hemochromatosis (HFE), transferrin (TF) C2, and heme oxygenase-1 (HMOX-1)]
      increase susceptibility to the effects of lead on QT interval in 613 community
      dwelling older men. METHODS: We used standard 12-lead electrocardiograms, K-shell
      X-ray fluorescence, and graphite furnace atomic absorption spectrometry to
      measure QT interval, bone lead, and blood lead levels, respectively. RESULTS: A
      one-interquartile-range increase in tibia lead level (13 mug/g) was associated
      with a 11.35-msec [95% confidence interval (CI), 4.05-18.65 msec] and a 6.81-msec
      (95% CI, 1.67-11.95 msec) increase in the heart-rate-corrected QT interval among
      persons carrying long HMOX-1 alleles and at least one copy of an HFE variant,
      respectively, but had no effect in persons with short and middle HMOX-1 alleles
      and the wild-type HFE genotype. The lengthening of the heart-rate-corrected QT
      interval with higher tibia lead and blood lead became more pronounced as the
      total number (0 vs. 1 vs. >/=2) of gene variants increased (tibia, p-trend =
      0.01; blood, p-trend = 0.04). This synergy seems to be driven by a joint effect
      between HFE variant and HMOX-1 L alleles. CONCLUSION: We found evidence that gene
      variants related to iron metabolism increase the impacts of low-level lead
      exposure on the prolonged QT interval. This is the first such report, so these
      results should be interpreted cautiously and need to be independently verified.

PMID- 19165392
TI  - Concentrations of phthalate metabolites in milk, urine, saliva, and Serum of
      lactating North Carolina women.
AB  - BACKGROUND: Phthalates are ubiquitous in the environment, but concentrations in
      multiple media from breast-feeding U.S. women have not been evaluated.
      OBJECTIVES: The objective of this study was to accurately measure and compare the
      concentrations of oxidative monoester phthalate metabolites in milk and surrogate
      fluids (serum, saliva, and urine) of 33 lactating North Carolina women. METHODS:
      We analyzed serum, saliva, urine, and milk for the oxidative phthalate
      metabolites mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-carboxypentyl)
      phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5
      oxohexyl) phthalate using isotope-dilution high-performance liquid chromatography
      tandem mass spectroscopy. Because only urine lacks esterases, we analyzed it for
      the hydrolytic phthalate monoesters. RESULTS: We detected phthalate metabolites
      in few milk (< 10%) and saliva samples. MECPP was detected in > 80% of serum
      samples, but other metabolites were less common (3-22%). Seven of the 10 urinary
      metabolites were detectable in > or = 85% of samples. Monoethyl phthalate had the
      highest mean concentration in urine. Metabolite concentrations differed by body
      fluid (urine > serum > milk and saliva). Questionnaire data suggest that frequent
      nail polish use, immunoglobulin A, and fasting serum glucose and triglyceride
      levels were increased among women with higher concentrations of urinary and/or
      serum phthalate metabolites; motor vehicle age was inversely correlated with
      certain urinary phthalate concentrations. CONCLUSIONS: Our data suggest that
      phthalate metabolites are most frequently detected in urine of lactating women
      and are less often detected in serum, milk, or saliva. Urinary phthalate
      concentrations reflect maternal exposure and do not represent the concentrations
      of oxidative metabolites in other body fluids, especially milk.

PMID- 19165393
TI  - Hydroxylated metabolites of polybrominated diphenyl ethers in human blood samples
      from the United States.
AB  - BACKGROUND: A previous study from our laboratory showed that polybrominated
      diphenyl ethers (PBDEs) were metabolized to hydroxylated PBDEs (HO-PBDEs) in mice
      and that para-HO-PBDEs were the most abundant and, potentially, the most toxic
      metabolites. OBJECTIVE: The goal of this study was to determine the
      concentrations of HO-PBDEs in blood from pregnant women, who had not been
      intentionally or occupationally exposed to these flame retardants, and from their
      newborn babies. METHODS: Twenty human blood samples were obtained from a hospital
      in Indianapolis, Indiana, and analyzed for both PBDEs and HO-PBDEs using electron
      capture negative-ionization gas chromatographic mass spectrometry. RESULTS: The
      metabolite pattern of HO-PBDEs in human blood was quite different from that found
      in mice; 5-HO-BDE-47 and 6-HO-BDE-47 were the most abundant metabolites of BDE
      47, and 5'-HO-BDE-99 and 6'-HO-BDE-99 were the most abundant metabolites of BDE
      99. The relative concentrations between precursor and corresponding metabolites
      indicated that BDE-99 was more likely to be metabolized than BDE-47 and BDE-100.
      In addition, three bromophenols were also detected as products of the cleavage of
      the diphenyl ether bond. The ratio of total hydroxylated metabolites relative to
      their PBDE precursors ranged from 0.10 to 2.8, indicating that hydroxylated
      metabolites of PBDEs were accumulated in human blood. CONCLUSIONS: The quite
      different PBDE metabolite pattern observed in humans versus mice indicates that
      different enzymes might be involved in the metabolic process. Although the levels
      of HO-PBDE metabolites found in human blood were low, these metabolites seemed to
      be accumulating.

PMID- 19165394
TI  - Dietary intake of methionine, cysteine, and protein and urinary arsenic excretion
      in Bangladesh.
AB  - BACKGROUND: In Bangladesh, millions of people are exposed to arsenic in drinking
      water; arsenic is associated with increased risk of cancer. Once ingested,
      arsenic is metabolized via methylation and excreted in urine. Knowledge about
      nutritional factors affecting individual variation in methylation is limited.
      OBJECTIVES: The purpose of this study was to examine associations between intakes
      of protein, methionine, and cysteine total urinary arsenic in a large population
      based sample. METHODS: The study subjects were 10,402 disease-free residents of
      Araihazar, Bangladesh, who participated in the Health Effects of Arsenic
      Longitudinal Study (HEALS). Food intakes were assessed using a validated food
      frequency questionnaire developed for the study population. Nutrient composition
      was determined by using the U.S. Department of Agriculture National Nutrient
      Database for Standard Reference. Generalized estimating equations were used to
      examine association between total urinary arsenic across quintiles of nutrient
      intakes while controlling for arsenic exposure from drinking water and other
      predictors of urinary arsenic. RESULTS: Greater intakes of protein, methionine,
      and cysteine were associated with 10-15% greater total urinary arsenic excretion,
      after controlling for total energy intake, body weight, sex, age, tobacco use,
      and intake of some other nutrients. CONCLUSIONS: Given previously reported risks
      between lower rates of arsenic excretion and increased rates of cancer, these
      findings support the role of nutrition in preventing arsenic-related disease.

PMID- 19165395
TI  - Associations between PM2.5 and heart rate variability are modified by particle
      composition and beta-blocker use in patients with coronary heart disease.
AB  - BACKGROUND: It has been hypothesized that ambient particulate air pollution is
      able to modify the autonomic nervous control of the heart, measured as heart rate
      variability (HRV). Previously we reported heterogeneous associations between
      particulate matter with aerodynamic diameter < 2.5 microm (PM2.5) and HRV across
      three study centers. OBJECTIVES: We evaluated whether exposure misclassification,
      effect modification by medication, or differences in particle composition could
      explain the inconsistencies. METHODS: Subjects with coronary heart disease
      visited clinics biweekly in Amsterdam, the Netherlands; Erfurt, Germany; and
      Helsinki, Finland for 6-8 months. The standard deviation (SD) of NN intervals on
      an electrocardiogram (ECG; SDNN) and high frequency (HF) power of HRV was
      measured with ambulatory ECG during paced breathing. Outdoor levels of PM2.5 were
      measured at a central site. In Amsterdam and Helsinki, indoor and personal PM2.5
      were measured during the 24 hr preceding the clinic visit. PM2.5 was apportioned
      between sources using principal component analyses. We analyzed associations of
      indoor/personal PM2.5, elements of PM2.5, and source-specific PM2.5 with HRV
      using linear regression. RESULTS: Indoor and personal PM2.5 were not associated
      with HRV. Increased outdoor PM2.5 was associated with decreased SDNN and HF at
      lags of 2 and 3 days only among persons not using beta-blocker medication.
      Traffic-related PM2.5 was associated with decreased SDNN, and long-range
      transported PM2.5 with decreased SDNN and HF, most strongly among persons not
      using beta blockers. Indicators for PM2.5 from traffic and long-range transport
      were also associated with decreased HRV. CONCLUSIONS: Our results suggest that
      differences in the composition of particles, beta-blocker use, and obesity of
      study subjects may explain some inconsistencies among previous studies on HRV.

PMID- 19165396
TI  - Long-term effects on hypothalamic neuropeptides after developmental exposure to
      chlorpyrifos in mice.
AB  - BACKGROUND: Increasing evidence from animal and human studies indicates that
      chlorpyrifos (CPF), similar to other organophosphorus insecticides still widely
      used, is a developmental neurotoxicant. Developmental exposure to CPF in rodents
      induces sex-dimorphic behavioral changes at adulthood, including social and
      agonistic responses, which suggests that CPF may interfere with maturation of
      neuroendocrine mechanisms. OBJECTIVES: We assessed the hypothesis that CPF
      affects the levels of neurohypophyseal hormones acting as modulators of social
      behavior in mammals, such as oxytocin (OT), arginine vasopressin (AVP), and
      prolactin (PRL). METHODS: Pregnant female mice were orally administered with
      either vehicle (peanut oil) or 3 or 6 mg/kg CPF on gestational day (GD) 15 to
      GD18, and offspring were treated subcutaneously with either vehicle or 1 or 3
      mg/kg CPF on postnatal days (PNDs) 11 to PND14. Dose levels were chosen to avoid
      systemic toxicity and inhibition of brain acetylcholinesterase. Offspring were
      sacrificed at 5 months of age, and expression of OT, AVP, and PRL was analyzed in
      the hypothalamus by Western blot or enzyme-linked immunosorbent assay (ELISA)
      analysis. RESULTS: Both male and female mice showed dose-related enhancement of
      OT expression, with males presenting the more intense effect. AVP expression was
      significantly reduced in male mice at the higher prenatal and postnatal dose. We
      observed no significant effect on PRL expression in either sex. Overall, outcomes
      were mainly attributable to fetal exposure, whereas postnatal doses appeared to
      potentiate the prenatal effects. CONCLUSIONS: Our data indicate that
      developmental exposure to CPF may permanently interfere with specific key
      signaling proteins of the hypothalamic peptidergic system, with time-, dose-, and
      sex-related effects still evident at adulthood.

PMID- 19165397
TI  - Meeting report: consensus statement-Parkinson's disease and the environment:
      collaborative on health and the environment and Parkinson's Action Network (CHE
      PAN) conference 26-28 June 2007.
AB  - BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative
      disorder. People with PD, their families, scientists, health care providers, and
      the general public are increasingly interested in identifying environmental
      contributors to PD risk. METHODS: In June 2007, a multidisciplinary group of
      experts gathered in Sunnyvale, California, USA, to assess what is known about the
      contribution of environmental factors to PD. RESULTS: We describe the conclusions
      around which they came to consensus with respect to environmental contributors to
      PD risk. We conclude with a brief summary of research needs. CONCLUSIONS: PD is a
      complex disorder, and multiple different pathogenic pathways and mechanisms can
      ultimately lead to PD. Within the individual there are many determinants of PD
      risk, and within populations, the causes of PD are heterogeneous. Although rare
      recognized genetic mutations are sufficient to cause PD, these account for < 10%
      of PD in the U.S. population, and incomplete penetrance suggests that
      environmental factors may be involved. Indeed, interplay among environmental
      factors and genetic makeup likely influences the risk of developing PD. There is
      a need for further understanding of how risk factors interact, and studying PD is
      likely to increase understanding of other neurodegenerative disorders.

PMID- 19165398
TI  - Intrauterine exposure to environmental pollutants and body mass index during the
      first 3 years of life.
AB  - OBJECTIVE: We investigated the association between body mass index (BMI) standard
      deviation score (SDS) and prenatal exposure to hexachlorobenzene,
      dichlorodiphenyldichloroethylene (DDE), dioxin-like compounds, and
      polychlorinated biphenyls (PCBs). METHODS: In this prospective birth cohort
      study, we assessed a random sample of mother-infant pairs (n = 138) living in
      Flanders, Belgium, with follow-up until the children were 3 years of age. We
      measured body mass index as standard deviation scores (BMI SDS) of children 1-3
      years of age as well as pollutants measured in cord blood. RESULTS: DDE
      correlated with BMI SDS, with effect modification by maternal smoking and the
      child's age. At 1 year, children of smoking mothers had higher BMI SDS than did
      children of nonsmoking mothers. At 3 years, this difference was reduced because
      of the faster rate of decline in BMI SDS in the former group. This relationship
      held except for children with high levels of DDE. DDE had a small effect on BMI
      SDS at 3 years of age in children of nonsmoking mothers (difference in BMI SDS
      for DDE concentrations between the 90th and 10th percentiles = 0.13). On the
      other hand, smoking enhanced the relation between DDE and BMI SDS at 3 years
      (difference in BMI SDS for DDE concentrations between the 90th and 10th
      percentiles = 0.76). Increasing concentrations of PCBs were associated with
      higher BMI SDS values at all ages (parameter estimate = 0.003 +/- 0.001; p =
      0.03). CONCLUSION: In this study we demonstrated that intrauterine exposure to
      DDE and PCBs is associated with BMI during early childhood. Future studies are
      warranted to confirm our findings and to assess possible mechanisms by which
      these pollutants could alter energy metabolism.

PMID- 19165399
TI  - Traffic-related air pollution and perinatal mortality: a case-control study.
AB  - BACKGROUND: Ambient levels of air pollution may affect the health of children, as
      indicated by studies of infant and perinatal mortality. Scientific evidence has
      also correlated low birth weight and preterm birth, which are important
      determinants of perinatal death, with air pollution. However, most of these
      studies used ambient concentrations measured at monitoring sites, which may not
      consider differential exposure to pollutants found at elevated concentrations
      near heavy-traffic roadways. OBJECTIVES: Our goal was to examine the association
      between traffic-related pollution and perinatal mortality. METHODS: We used the
      information collected for a case-control study conducted in 14 districts in the
      City of Sao Paulo, Brazil, regarding risk factors for perinatal deaths. We
      geocoded the residential addresses of cases (fetal and early neonatal deaths) and
      controls (children who survived the 28th day of life) and calculated a distance
      weighted traffic density (DWTD) measure considering all roads contained in a
      buffer surrounding these homes. RESULTS: Logistic regression revealed a gradient
      of increasing risk of early neonatal death with higher exposure to traffic
      related air pollution. Mothers exposed to the highest quartile of the DWTD
      compared with those less exposed exhibited approximately 50% increased risk
      (adjusted odds ratio = 1.47; 95% confidence interval, 0.67-3.19). Associations
      for fetal mortality were less consistent. CONCLUSIONS: These results suggest that
      motor vehicle exhaust exposures may be a risk factor for perinatal mortality.

PMID- 19165400
TI  - Household exposure to paint and petroleum solvents, chromosomal translocations,
      and the risk of childhood leukemia.
AB  - BACKGROUND: Few studies have examined the association between home use of
      solvents and paint and the risk of childhood leukemia. OBJECTIVES: In this case
      control study, we examined whether the use of paint and petroleum solvents at
      home before birth and in early childhood influenced the risk of leukemia in
      children. METHODS: We based our analyses on 550 cases of acute lymphoblastic
      leukemia (ALL), 100 cases of acute myeloid leukemia (AML), and one or two
      controls per case individually matched for sex, age, Hispanic status, and race.
      We conducted further analyses by cytogenetic subtype. We used conditional
      logistic regression techniques to adjust for income. RESULTS: ALL risk was
      significantly associated with paint exposure [odds ratio (OR) = 1.65; 95%
      confidence interval (CI), 1.26-2.15], with a higher risk observed when paint was
      used postnatally, by a person other than the mother, or frequently. The
      association was restricted to leukemia with translocations between chromosomes 12
      and 21 (OR = 4.16; 95% CI, 1.66-10.4). We found no significant association
      between solvent use and ALL risk overall (OR = 1.15; 95% CI, 0.87-1.51) or for
      various cytogenetic subtypes, but we observed a significant association in the
      2.0- to 5.9-year age group (OR = 1.55; 95% CI, 1.07-2.25). In contrast, a
      significant increased risk for AML was associated with solvent (OR = 2.54; 95%
      CI, 1.19-5.42) but not with paint exposure (OR = 0.64; 95% CI, 0.32-1.25).
      CONCLUSIONS: The association of ALL risk with paint exposure was strong,
      consistent with a causal relationship, but further studies are needed to confirm
      the association of ALL and AML risk with solvent exposure.

PMID- 19165401
TI  - Air pollution and childhood respiratory allergies in the United States.
AB  - BACKGROUND: Childhood respiratory allergies, which contribute to missed school
      days and other activity limitations, have increased in recent years, possibly due
      to environmental factors. OBJECTIVE: In this study we examined whether air
      pollutants are associated with childhood respiratory allergies in the United
      States. METHODS: For the approximately 70,000 children from the 1999-2005
      National Health Interview Survey eligible for this study, we assigned between
      40,000 and 60,000 ambient pollution monitoring data from the U.S. Environmental
      Protection Agency, depending on the pollutant. We used monitors within 20 miles
      of the child's residential block group. We used logistic regression models, fit
      with methods for complex surveys, to examine the associations between the
      reporting of respiratory allergy or hay fever and annual average exposure to
      particulate matter < or = 2.5 microm in diameter (PM2.5), PM < or = 10 microm in
      diameter, sulfur dioxide, and nitrogen dioxide and summer exposure to ozone,
      controlling for demographic and geographic factors. RESULTS: Increased
      respiratory allergy/hay fever was associated with increased summer O3 levels
      [adjusted odds ratio (AOR) per 10 ppb = 1.20; 95% confidence interval (CI), 1.15
      1.26] and increased PM2.5 (AOR per 10 microg/m3 = 1.23; 95% CI, 1.10-1.38). These
      associations persisted after stratification by urban-rural status, inclusion of
      multiple pollutants, and definition of exposures by differing exposure radii. No
      associations between the other pollutants and the reporting respiratory
      allergy/hay fever were apparent. CONCLUSIONS: These results provide evidence of
      adverse health for children living in areas with chronic exposure to higher
      levels of O3 and PM2.5 compared with children with lower exposures.

PMID- 19165402
TI  - Windblown lead carbonate as the main source of lead in blood of children from a
      seaside community: an example of local birds as "canaries in the mine".
AB  - BACKGROUND: In late 2006, the seaside community in Esperance, Western Australia,
      was alerted to thousands of native bird species dying. The source of the lead was
      thought to derive from the handling of Pb carbonate concentrate from the Magellan
      mine through the port of Esperance, begun in July 2005. Concern was expressed for
      the impact of this process on the community. OBJECTIVE: This study was designed
      to evaluate the source of Pb in blood of a random sample of the community using
      Pb isotope ratios. METHODS: The cohort comprised 49 children (48 < 5 years of
      age) along with 18 adults (> 20 years of age) with a bias toward higher blood
      lead (PbB) values to facilitate source identification. RESULTS: Mean PbB level of
      the children was 7.5 microg/dL (range, 1.5-25.7 microg/dL; n = 49; geometric
      mean, 6.6 microg/dL), with four children whose PbB was > 12 microg/dL. The
      isotopic data for blood samples lay around two distinct arrays. The blood of all
      children analyzed for Pb isotopes contained a contribution of Pb from the
      Magellan mine, which for young children ranged from 27% up to 93% (mean, 64%;
      median, 71%). Subtraction of the ore component gave a mean background PbB of 2.3
      mug/dL. Several children whose PbB was > 9 microg/dL and most of the older
      subjects have complex sources of Pb. CONCLUSIONS: The death of the birds acted as
      a sentinel event; otherwise, the exposure of the community, arising from such a
      toxic form of Pb, could have been tragic. Isotopic data and mineralogic and
      particle size analyses indicate that, apart from the recognized pathway of Pb
      exposure by hand-to-mouth activity in children, the inhalation pathway could have
      been a significant contributor to PbB for some of the very young children and in
      some parents.

PMID- 19165404
TI  - Determination of heavy metal toxicity of finished leather solid waste.
AB  - This paper investigates the toxicity in leather products of heavy metals known to
      be detrimental to the ecosystem. Heavy metal concentrations in leather samples
      were identified with ICP-OES, and toxicity was determined using a MetPLATE
      bioassay. Chromium and aluminium were found to constitute 98% of the total
      concentration of heavy metals in finished leather tanned with chromium and
      aluminium salts, while in some vegetable-tanned leather, zirconium was the only
      heavy metal identified. The average inhibition values for chromium, aluminium and
      vegetable tanned leather were 98.08%, 97.04% and 62.36%, respectively.

PMID- 19165403
TI  - Assessing local instrument reliability and validity: a field-based example from
      northern Uganda.
AB  - This paper presents an approach for evaluating the reliability and validity of
      mental health measures in non-Western field settings. We describe this approach
      using the example of our development of the Acholi psychosocial assessment
      instrument (APAI), which is designed to assess depression-like (two tam, par and
      kumu), anxiety-like (ma lwor) and conduct problems (kwo maraco) among war
      affected adolescents in northern Uganda. To examine the criterion validity of
      this measure in the absence of a traditional gold standard, we derived local
      syndrome terms from qualitative data and used self reports of these syndromes by
      indigenous people as a reference point for determining caseness. Reliability was
      examined using standard test-retest and inter-rater methods. Each of the subscale
      scores for the depression-like syndromes exhibited strong internal reliability
      ranging from alpha = 0.84-0.87. Internal reliability was good for anxiety (0.70),
      conduct problems (0.83), and the pro-social attitudes and behaviors (0.70)
      subscales. Combined inter-rater reliability and test-retest reliability were good
      for most subscales except for the conduct problem scale and prosocial scales. The
      pattern of significant mean differences in the corresponding APAI problem scale
      score between self-reported cases vs. noncases on local syndrome terms was
      confirmed in the data for all of the three depression-like syndromes, but not for
      the anxiety-like syndrome ma lwor or the conduct problem kwo maraco.

PMID- 19165405
TI  - Hydrolysis and photolysis of diacylhydrazines-type insect growth regulator JS-118
      in aqueous solutions under abiotic conditions.
AB  - JS-118 is a diacylhydrazines-type insect growth regulator which is now used
      extensively in China. The hydrolysis and photolysis of the pesticide JS-118 in
      aqueous solutions have been assessed under natural and controlled conditions in
      this project. Hydrolysis experimental results show that JS-118 is quite stable in
      aqueous solutions in dark, with no significant variations be observed in
      degradation under various conditions. Abiotic hydrolysis is relatively
      unimportant compared to photolysis. The rate of photodecomposition of JS-118 in
      aqueous solutions follows first-order kinetics both in UV radiation and natural
      sunlight. The degradation rates are faster under UV light than sunlight, with the
      half-lives (t (1/2) = ln2/k) of 6.00-10.85 min and 6.63-10.16 day, respectively.
      Under UV light, two major photoproducts are detected, and tentatively identified
      according to HPLC-MS spectral information as N-t-butyl-N-(3,5-dimethylbenzoyl)
      and 3,7-dimethyl-benzoatedihydrofuran. The corresponding photolysis pathways of
      JS-118 are also proposed. The results obtained indicate that direct photoreaction
      is an important dissipation pathway of JS-118 in natural water systems.

PMID- 19165406
TI  - Role of waterborne copper on survival, growth and feed intake of Indian major
      carp, Cirrhinus mrigala Hamilton.
AB  - The effect of copper on survival, growth and feed intake of Indian major carp,
      Cirrhinus mrigala (Hamilton) fry (0.92 +/- 0.28 g) was studied for 60 days.
      Survival rates of the fish exposed to control (0.02), 0.10, 0.15 and 0.23 mg L(
      1) copper were 100%, 83 +/- 3%, 58 +/- 6%, and 50 +/- 4%, respectively. Average
      daily growth was significantly (p < 0.05) lower at 0.15 and 0.23 mg L(-1) of
      copper. There was almost no growth at 0.23 mg L(-1) of copper. Feed intake rates
      reduced significantly (p < 0.05) at all the copper treatments. The copper
      accumulation in the fish increased with increasing concentrations of the metal.

PMID- 19165407
TI  - Accumulation and resistance to copper of two biotypes of Cynodon dactylon.
AB  - The effects of copper accumulation and resistance in two biotypes of Cynodon
      dactylon were studied. Results showed that at a low concentration of copper (<100
      mg/kg), the growth of Cynodon dactylon was generally unaffected. As copper
      concentration increased, negative effects on the growth of Cynodon dactylon
      became apparent. The critical concentration at which the plant exhibited
      poisoning symptoms was different for the two biotypes of Cynodon dactylon. At 500
      mg/kg copper concentration in soil, the biotype from the polluted area showed
      significantly higher tolerance of copper than the biotype from the unpolluted
      area.

PMID- 19165408
TI  - Residue, temporal trend and half-life time of selected organochlorine pesticides
      (OCPs) in surface soils from Bacninh, Vietnam.
AB  - Selected organochlorine pesticides (p,p'-DDT, p,p'-DDE, p,p'-DDD,
      alpha,beta,gamma,delta-HCH) were analyzed in the surface soils of Bacninh, Viet
      Nam. Forty representative soil samples were collected from Bacninh town and three
      surrounding districts. SigmaDDT concentrations ranged from <0.02 to 160.86 ng g(
      1) dry weight, whereas SigmaHCH concentrations ranged from <0.05 to 9.54 ng g(-1)
      dry weight. The half-life times of SigmaDDT and SigmaHCH are 6.7 and 4.9 years,
      respectively. The decreasing trends of SigmaDDT and SigmaHCH levels during the
      period from 1992 to 2006 are observed. There is no recent input of DDT and HCH in
      the study area.

PMID- 19165409
TI  - Preliminary risk assessment of trace metal pollution in surface water from
      Yangtze River in Nanjing Section, China.
AB  - In order to investigate the contamination levels of trace metals, surface water
      samples were collected from six regions along Yangtze River in Nanjing Section.
      The concentrations of trace metals (As, B, Ba, Be, Cd, Cr, Cu, Fe, Pb, Li, Mn,
      Mo, Ni, Sb, Se, Sn, Sr, V and Zn) were determined using inductively coupled
      plasma-atomic emission spectrometry (ICP-AES). Total concentrations of the metals
      in the water samples ranged from 825.1 to 950.4 microg/L. The result was compared
      with international water quality guidelines. Seven metals levels were above the
      permissible limit as prescribed by guidelines. A preliminary risk assessment was
      then carried out to determine the human health risk via calculating Hazard
      Quotient and carcinogenic risk of the metals. Hazard Quotients of all metals were
      lower than unity, except As. The carcinogenic risk of As and Cd was higher than
      10(-6), suggesting that those two metals have potential adverse effects on local
      residents.

PMID- 19165410
TI  - An ecological risk assessment of the exposure and effects of 2,4-D acid to
      rainbow trout (Onchorhyncus mykiss).
AB  - Numerous state and federal agencies are increasingly concerned with the rapid
      expansion of invasive, noxious weeds across the United States. Herbicides are
      frequently applied as weed control measures in forest and rangeland ecosystems
      that frequently overlap with critical habitats of threatened and endangered fish
      species. However, there is little published chronic toxicity data for herbicides
      and fish that can be used to assess ecological risk of herbicides in aquatic
      environments. We conducted 96-h flowthrough acute and 30-day chronic toxicity
      studies with swim-up larvae and juvenile rainbow trout (Onchorhyncus mykiss)
      exposed to the free acid form of 2,4-D. Juvenile rainbow trout were acutely
      sensitive to 2,4-D acid equivalent at 494 mg/L (95% confidence interval [CI] 334
      668 mg/L; 96-h ALC(50)). Accelerated life-testing procedures, used to estimate
      chronic mortality from acute data, predicted that a 30-day exposure of juvenile
      rainbow trout to 2,4-D would result in 1% and 10% mortality at 260 and 343 mg/L,
      respectively. Swim-up larvae were chronically more sensitive than juveniles using
      growth as the measurement end point. The 30-day lowest observable effect
      concentration (LOEC) of 2,4-D on growth of swim-up larvae was 108 mg/L, whereas
      the 30-day no observable effect concentration (NOEC) was 54 mg/L. The 30-day
      maximum acceptable toxicant concentration (MATC) of 2,4-D for rainbow trout,
      determined as the geometric mean of the NOEC and the LOEC, was 76 mg/L. The
      acute:chronic ratio was 6.5 (i.e., 494/76). We observed no chronic effects on
      growth of juvenile rainbow trout at the highest concentration tested (108 mg/L).
      Worst-case aquatic exposures to 2,4-D (4 mg/L) occur when the herbicide is
      directly applied to aquatic ecosystems for aquatic weed control and resulted in a
      30-day safety factor of 19 based on the MATC for growth (i.e., 76/4). Highest
      nontarget aquatic exposures to 2,4-D applied following terrestrial use is
      calculated at 0.136 mg/L and resulted in a 30-day safety factor of 559 (e.g.,
      76/0.163). Assessment of the exposure and response data presented herein
      indicates that use of 2,4-D acid for invasive weed control in aquatic and
      terrestrial habitats poses no substantial risk to growth or survival of rainbow
      trout or other salmonids, including the threatened bull trout (Salvelinus
      confluentus).

PMID- 19165411
TI  - Women with SUI demonstrate motor control differences during voluntary pelvic
      floor muscle contractions.
AB  - INTRODUCTION AND HYPOTHESIS: To compare maximum abdominal and pelvic floor muscle
      (PFM) electromyographic (EMG) and intravaginal pressure (IVP) amplitudes and
      muscle activation patterns during voluntary PFM contractions between women with
      and without stress urinary incontinence (SUI). METHODS: Twenty-eight continent
      women and 44 women with SUI performed single and repeated PFM contractions in
      supine. Surface EMG data were recorded simultaneously with IVP. Maximum EMG and
      IVP amplitudes and ensemble average IVP versus EMG curves were determined from
      the single contractions. Muscle activation timing was determined with cross
      correlation functions from the repeated contractions. RESULTS: The continent
      group produced higher PFM EMG amplitudes than the SUI group; there were no
      between group differences in IVP. The women with SUI delayed activating rectus
      abdominus. The IVP versus EMG curves' shapes were similar between the groups,
      however the SUI group had higher abdominal muscle y-intercepts than the continent
      women. CONCLUSIONS: These findings suggest that women with SUI demonstrate
      altered motor control strategies during voluntary PFM contractions.

PMID- 19165412
TI  - Prophylactic ureteral catheterization in gynecologic surgery: a 12-year
      randomized trial in a community hospital.
AB  - INTRODUCTION: The aim of this study is to determine the efficacy of preoperative
      ureteral catheterization as a prophylactic measure to prevent ureteral injury and
      related complications. METHODS: All major gynecologic operations performed
      between January 1996 and December 2007 were included and prospectively randomized
      into with and without catheterization groups. The medical records allowed the
      identification of all urinary tract complications and ureteral injuries. RESULTS:
      Bilateral prophylactic ureteral catheterization was performed in 1,583 patients.
      A ureteral injury occurred in 19 (1.20%) out of 1,583 patients. Seventeen
      ureteral injuries (1.09%) occurred out of 1,558 patients without prophylactic
      ureteral catheterization. There was no statistically significant difference in
      the incidence of ureteral injury between the different interventional groups (p =
      0.774). CONCLUSION: The use of prophylactic ureteral catheters did not eliminate
      ureteral injuries in our patients. The presence of ureteral catheters should not
      supplant meticulous surgical techniques and direct visualization of the ureters
      during gynecologic surgery.

PMID- 19165413
TI  - Torsion of the gallbladder in a 3-year-old infant.
AB  - A 3-year-old girl was admitted to hospital with complaints of severe upper
      abdominal pain and vomiting. On admission, a board-like rigidity in the right
      hypochondrium was noted, along with a high white blood cell count and a high C
      reactive protein value. Abdominal ultrasonography (US) revealed a left-sided
      enlarged gallbladder with a thickened wall, without gallstones. Contrast-enhanced
      computed tomography (CT) demonstrated an enlarged gallbladder without enhancement
      effects and a cystic duct located on the right side of the gallbladder. The
      patient underwent an emergency operation following a diagnosis of torsion of the
      gallbladder. The gallbladder appeared gangrenous, and 180 degrees clockwise
      torsion was found at the neck of the gallbladder. The gallbladder was
      straightened and then removed without difficulty because there was only slight
      inflammation around Calot's triangle and the gallbladder was not fixed to the
      liver. Histopathological examination revealed an acute bleeding infarction of the
      gallbladder. The patient was discharged on the ninth day after surgery, without
      any complications. The present case suggested that abdominal US and contrast
      enhanced CT examinations are helpful in making a correct diagnosis of torsion of
      the gallbladder even in an infant; in the event of this diagnosis, prompt
      cholecystectomy is necessary.

PMID- 19165414
TI  - Graft size and donor age are independent factors for graft loss in adult-to-adult
      living-donor liver transplantation using the left liver.
AB  - BACKGROUND/PURPOSE: Graft survival is affected by various factors, such as
      preoperative state and the ages of the recipient and donor, as well as graft
      size. The objective of this study was to analyze the risk factors for graft
      survival. METHODS: From September 1997 to July 2005, 24 patients who had
      undergone living-donor liver transplantation (LDLT) were retrospectively
      analyzed. Sixteen patients survived and the eight graft-loss cases were
      classified into two groups according to the cause of graft loss: graft
      dysfunction without major post-transplantation complications (graft dysfunction
      group; n = 3), and graft dysfunction with such complications (secondary graft
      dysfunction group; n = 5). Various factors were compared between these groups and
      the survival group. RESULTS: Mean donor age was 31.9 years in the survival group
      and 49.2 years in the secondary graft dysfunction group (P = 0.024). Graft
      weight/recipient standard liver volume ratios (G/SLVs) were 36.7% in the survival
      group, and 26.2% in the graft dysfunction group (P = 0.037). The postoperative
      mean PT% for 1 week was 48.6% in the survival group and 38.1% in the secondary
      graft dysfunction group (P = 0.05). CONCLUSIONS: Our surgical results
      demonstrated that G/SLV and donor age were independent factors that affected
      graft survival rates.

PMID- 19165415
TI  - Clinical islet transplantation in Japan.
AB  - INTRODUCTION: The results of clinical islet transplantation in Japan are, here
      in, reported and discussed its efficacy and problems. METHODS: Since the first
      islet transplantation was performed in 2004, 65 islet isolations and 34 islet
      transplantations to 18 type 1 diabetic patients have been performed in Japan.
      RESULTS: Following islet transplantation, patients experienced decreased insulin
      requirements and lower hemoglobin A1C levels, and positive serum C-peptide
      levels. All patients achieved stabilized blood glucose levels and the
      disappearance of hypoglycemic unawareness. Although three patients achieved
      insulin independency for a limited period, persistent islet graft function was
      difficult to maintain. Overall islet graft survival was 86.5% at 6 months, 78.7%
      at 1 year, and 62.9% at 2 years after the first islet transplantation. In our
      institution, we carried out 23 islet isolations and six islet transplantations to
      four patients. Although insulin independency was not achieved, all patients
      showed a disappearance of hypoglycemic unawareness. CONCLUSIONS: Using data from
      the Japanese Trial of Islet Transplantation, the effectiveness of islet
      transplantation was shown even when using the pancreata from non-heart-beating
      donors. Although there are a number of problems to be solved and further
      improvement is needed, we can state that the introduction of clinical islet
      transplantation offers hope for type 1 diabetic patients.

PMID- 19165416
TI  - Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: unusual
      clinical associations and novel claudin16 mutation in an Egyptian family.
AB  - BACKGROUND: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis
      (FHHNC) is a rare autosomal recessive tubular disorder that eventually progresses
      to renal failure, depending upon the extent of nephrocalcinosis. Its basic
      pathogenesis is impaired tubular resorption of magnesium and calcium in the thick
      ascending limb of the loop of Henle (TAL) due to a genetic defect in paracellin-1
      (a tight junction protein expressed in TAL). Mutations of the claudin16 gene
      (CLDN16), formerly called paracellin-1 gene (PCLN-1), have been linked to FHHNC.
      METHODS: An extended Egyptian family with more than one member affection by
      nephrocalcionsis was included and thoroughly investigated in the current study
      after giving informed consent. Thorough history was taken for polyuria,
      polydipsia and hypocalcemia symptoms, as well as clinical examination with stress
      on anthropometric measurements and radiological evaluation for kidneys and bones.
      Laboratory workup for the differential diagnosis of nephrocalcinosis was done:
      complete urinalysis, including urinary calcium excretion, urine pH and
      electrolytes, arterial blood gas (ABG), serum electrolytes (sodium, potassium,
      calcium, magnesium and phosphorous), renal function tests as well as parathyroid
      and gonadotropin-sex hormone assay. DNA extraction from peripheral blood
      leukocytes was done followed by amplification using primers previously described,
      purification and finally sequencing to analyze each exon of the CLDN16 gene.
      RESULTS: Two sibs for a consanguineous couple were affected by nephrocalcinosis
      and showed persistent hypocalcemia, hypercalciuria, nephrocalcinosis with
      persistently alkaline urine and ocular manifestations in the form of congenital
      cataracts, high myopia and retinal abnormalities. The elder sib showed
      genitourinary abnormalities in the form of hypospadias and cryptorchidism. These
      two sibs had a homozygous two-base deletion in exon 1 of the CLDN16 gene (C.
      233_234 del GG; Ins C), causing a frame shift mutation (Arg55 fs); however, their
      parents were heterozygote carriers for that mutation. CONCLUSION: The above
      mentioned clinical data in the two affected sibs together with the family history
      of end-stage renal disease associated with nephrocalcinosis and high myopia
      suggested a diagnosis of FHHNC, which was confirmed for the first time in an
      Egyptian family by a novel mutation in exon 1 of the CLDN16 gene. Genitourinary
      associations with FHHNC have not yet been reported in the literature. Here, we
      will try to highlight the principles of mutation detection based on sequencing
      with the use of the online NCBI databases, statistics and other search tools.

PMID- 19165417
TI  - Molecular characterization of two alphacryptovirus dsRNAs isolated from Daucus
      carota.

PMID- 19165418
TI  - The Notch signaling pathway: transcriptional regulation at Notch target genes.
AB  - The Notch gene encodes a transmembrane receptor that gave the name to the
      evolutionary highly conserved Notch signaling cascade. It plays a pivotal role in
      the regulation of many fundamental cellular processes such as proliferation, stem
      cell maintenance and differentiation during embryonic and adult development.
      After specific ligand binding, the intracellular part of the Notch receptor is
      cleaved off and translocates to the nucleus, where it binds to the transcription
      factor RBP-J. In the absence of activated Notch, RBP-J represses Notch target
      genes by recruiting a corepressor complex. Here, we review Notch signaling with a
      focus on gene regulatory events at Notch target genes. This is of utmost
      importance to understand Notch signaling since certain RBP-J associated cofactors
      and particular epigenetic marks determine the specificity of Notch target gene
      expression in different cell types. We subsequently summarize the current
      knowledge about Notch target genes and the physiological significance of Notch
      signaling in development and cancer.

PMID- 19165419
TI  - c-Met-targeted RNA interference inhibits growth and metastasis of glioma U251
      cells in vitro.
AB  - Angiogenesis plays an essential role in tumor growth and metastasis and is a
      promising target for cancer therapy. c-Met, a receptor tyrosine kinase, and its
      ligand, hepatocyte growth factor (HGF), are critical in cellular proliferation,
      motility, invasion, and angiogenesis. The present study was designed to determine
      the role of c-Met in growth and metastasis of glioma U251 cells using RNA
      interference (RNAi) technology in vitro. We constructed three kinds of shRNA
      expression vectors aiming at the c-Met gene, then transfected them into glioma
      U251 cells by lipofectamine(TM) 2000. The level of c-Met mRNA was investigated by
      real-time polymerse chain reaction (RT-PCR). The protein expression of c-Met was
      observed by immunofluoresence staining and western blotting. U251 cell growth and
      adherence was detected by methyl thiazole tetrazolium assay. The apoptosis of
      U251 cells was examined with a flow cytometer. The adherence, invasion, and in
      vitro angiogenesis assays of U251 cells were done. We got three kinds of c-Met
      specific shRNA expression vectors which could efficiently inhibit the growth and
      metastasis of U251 cells and the expression of c-Met in U251 cells. RT-PCR,
      immunofluoresence staining and western blotting showed that inhibition rate for c
      Met expression was up to 90%, 79% and 85%, respectively. The expression of c-Met
      can be inhibited by RNA interference in U251 cells, which can inhibit the growth
      and metastasis of U251 cell and induce cell apoptosis. These results indicate
      that RNAi of c-Met can be an effective antiangiogenic strategy for glioma.

PMID- 19165421
TI  - Macular sensitivity changes for detection of chloroquine toxicity in asymptomatic
      patient.
AB  - PURPOSE: To describe the efficacy of microperimetry (MP-1) in detecting early
      retinal toxicity as a result of chronic use of chloroquine and in monitoring the
      changes in macular sensitivity in an asymptomatic patient with best-corrected
      visual acuity of 20/20 bilaterally. METHODS: A 60-year-old woman presented for
      routine ocular examination with a medical history of severe rheumatoid arthritis,
      for which she had been receiving 3 mg chloroquine (CQ) per kilogram for the past
      17 years. The patient was asymptomatic with best-corrected visual acuity of 20/20
      bilaterally. RESULTS: Microperimeter showed loss of sensitivity in the macular
      region with a dense scotoma within the central 12 degrees (2.80 +/- 4.7 dB right
      eye and 2.84 +/- 4.7 dB left eye). CQ treatment was discontinued and substituted
      by Plaquenil. CONCLUSIONS: Chloroquine retinal toxicity can be recognized in a
      subclincal form by the presence of early changes in macular sensitivity, detected
      by MP-1.

PMID- 19165422
TI  - Outcome of primary adult optical penetrating keratoplasty with imported donor
      corneas.
AB  - PURPOSE: To evaluate the outcome of primary adult optical penetrating
      keratoplasty (PKP) performed with internationally acquired donor tissue. PATIENTS
      AND METHODS: A retrospective review was performed of the medical records of every
      patient 12 years of age or older who underwent PKP for keratoconus, corneal
      edema, stromal scarring, or stromal dystrophy at King Khaled Eye Specialist
      Hospital in the Kingdom of Saudi Arabia between January 1, 1997 and December 31,
      2001, and for whom a minimum of 3 months' follow-up was available. RESULTS: Of
      885 eyes that met the inclusion criteria, there were 453 eyes with keratoconus,
      180 eyes with corneal edema, 171 eyes with stromal scarring, and 81 eyes with
      stromal dystrophy. For the entire group, the probability of graft survival was
      96.9% at 1 year, 86.0% at 3 years, and 80.3% at 5 years. The 5-year probability
      of graft survival was 96.2% for keratoconus, 39.4% for corneal edema, 71.1% for
      stromal scarring, and 85.2% for stromal dystrophy. Increasing donor age was
      significantly associated with an increased risk of graft failure on multivariate
      Cox proportional hazard regression analysis (P = 0.005). Endothelial cell
      density, death-to-preservation time, and preservation-to-surgery time were not
      significantly associated with an increased risk of graft failure. CONCLUSIONS: In
      our patient population, excellent graft survival was achieved utilizing
      internationally acquired donor tissue for eyes with keratoconus, stromal
      dystrophy, and stromal scarring, but not for those with corneal edema.

PMID- 19165420
TI  - Pak protein kinases and their role in cancer.
AB  - Some of the characteristics of cancer cells are high rates of cell proliferation,
      cell survival, and the ability to invade surrounding tissue. The cytoskeleton has
      an essential role in these processes. Dynamic changes in the cytoskeleton are
      necessary for cell motility and cancer cells are dependent on motility for
      invasion and metastasis. The signaling pathways behind the reshaping and
      migrating properties of the cytoskeleton in cancer cells involve a group of Ras
      related small GTPases and their effectors, including the p21-activated kinases
      (Paks). Paks are a family of serine/threonine protein kinases comprised of six
      isoforms (Pak 1-6), all of which are direct targets of the small GTPases Rac and
      Cdc42. Besides their role in cytoskeletal dynamics, Paks have recently been shown
      to regulate various other cellular activities, including cell survival, mitosis,
      and transcription. Paks are overexpressed and/or hyperactivated in several human
      tumors and their role in cell transformation makes them attractive therapeutic
      targets. Pak-targeted therapeutics may efficiently inhibit certain types of
      tumors and efforts to identify selective Pak-inhibitors are underway.

PMID- 19165423
TI  - Epidemic of unilateral panuveitis in children from Brazilian Amazonia: clinical
      and etiological aspects in seven patients.
AB  - OBJECTIVES: To describe clinical presentation and results of diagnostic and
      therapeutic procedures in seven children from an epidemic of panuveitis in the
      Brazilian Amazonia, as well as environmental analysis and etiological aspects
      involved. METHODS: Patients underwent full pediatric and ophthalmic examinations,
      B-scan, ultrasound biomicroscopy, and serological tests. Ocular samples were
      thoroughly analyzed, including two enucleation specimens. Environmental
      investigation encompassed water, soil, and river fauna. RESULTS: All patients had
      bathed in the waters of a regional river, the Araguaia. Six of them presented
      with intermediate uveitis, with snowbanking. Five had cataract and four showed
      inferior endothelial opacity, with localized anterior synechiae. One showed total
      leukoma, with flat anterior chamber. Only two had active uveitis, one of them
      with anterior chamber nodule. Serology revealed high prevalence of anti-Toxocara
      canis immunoglobulin G (IgG) antibodies. In three cases, vitreous and lens
      samples disclosed spicules of freshwater sponges Drulia uruguayensis and D.
      ctenosclera, also detected in the waters of the river. CONCLUSION: Freshwater
      sponge spicules could be potential new etiological agents of ocular pathology,
      but further studies are needed, considering the heterogeneity of the ocular
      lesions and results of serological and environmental studies.

PMID- 19165424
TI  - Role of intravitreal bevacizumab in the management of Eales' disease.
AB  - PURPOSE: To evaluate the role of intravitreal bevacizumab in the treatment of
      Eales' disease. Study design Retrospective, interventional case series. METHODS:
      Two patients with proliferative Eales' disease were managed with an intravitreal
      injection of bevacizumab (1.25 mg). The presence of persistent retinal
      neovascularization despite adequate laser photocoagulation caused recurrent
      episodes of vitreous hemorrhage in the first patient. The second patient had
      florid retinal and disc neovascularization with a dispersed vitreous bleed, which
      prevented laser therapy. Both patients were followed up for 6 months. RESULTS:
      Rapid regression of the retinal neovascularization and clearing of the vitreous
      hemorrhage were observed in both cases following intravitreal bevacizumab
      therapy, allowing laser photocoagulation. In both patients, the visual acuity
      improved, and no signs of recurrence were observed 6 months post-treatment.
      CONCLUSION: Intravitreal bevacizumab injections may be effective as an adjunctive
      or alternative treatment of retinal neovascularization in Eales' disease, where
      inadequate visualization precludes laser photocoagulation. This approach may also
      be useful in avoiding vitreoretinal surgical intervention in certain cases.
      Intravitreal bevacizumab was well tolerated by our patients, and no adverse
      effects were observed.

PMID- 19165425
TI  - Serum and cerebrospinal fluid magnesium levels, Glasgow Coma Scores, and in
      hospital mortality in patients with acute stroke.
AB  - The aim of this study was to determine the relationship between serum and
      cerebrospinal fluid (CSF) magnesium(Mg+2) levels, Glasgow Coma Scores (GCS), and
      7-day mortality in acute stroke patients. Patients with acute ischemic or
      hemorrhagic stroke arriving within the first 3 h of symptoms were included in the
      study. The control group consisted of healthy volunteers. GCS was determined, and
      blood and CSF samples were taken in order to establish serum and CSF glucose,
      Mg+2, sodium, potassium, calcium, and chlorine levels.Mortality was recorded at 7
      days after admission. CSF Mg+2 in the ischemic infarct group was significantly
      lower than in the control group (p=0.006). CSF Mg+2 in the ischemic infarct
      patients with a GCS < or = 8 were significantly lower (p=0.002) than controls and
      in ischemic infarct patients with a GCS > or = 9. In the ischemic stroke
      patients, CSF Mg+2 and GCS were significantly correlated (r=55, p=0.031). CSF
      Mg+2 levels in ischemic stroke patients who died within 7 days were significantly
      lower than controls, ischemic stroke patients who survived, and hemorrhagic
      stroke patients who died (p=0.002, p=0.042, and p=0.005,respectively). Low CSF
      Mg+2 levels in patients with acute ischemic stoke at admission predicted a higher
      1-week mortality.

PMID- 19165426
TI  - Zinc, copper, iron, and selenium levels in brain and liver of mice exposed to
      acrylonitrile.
AB  - The mechanism of toxicity of acrylonitrile (AN) has not been fully defined. The
      research described herein was undertaken to investigate the possible effects of
      AN on the levels of metallic elements in liver and brain of mice. Thirty-two mice
      were randomly assigned to four separate groups and treated intraperitoneal (i.p.)
      once daily for 1 week. Mice in the control group received normal saline, and mice
      in the three exposure groups received 5, 10, or 20 mg AN/kg b.w. Samples of brain
      and liver were collected immediately after decapitation. Tissue levels of trace
      elements (zinc, copper, iron) were determined with flame atomic absorption
      spectrophotometer or double channel atomic fluorescence absorption
      spectrophotometer (selenium). Mean brain weights of AN-treated mice were
      increased as a function of dose compared to controls, but there was no
      significant change in the ratio of liver/body weight in the four groups. While
      mean brain zinc decreased as a function of AN dosage, mean liver zinc of the low
      dose group significantly increased (p < 0.05); mean liver copper in the medium
      dose AN group was significantly higher compared to controls (p < 0.05); however,
      mean brain copper was increased, but the difference did not attain statistical
      significance in the three AN groups when compared with the controls (p > 0.05).
      Mean brain iron levels were significantly decreased in the middle-dose AN group
      (p < 0.05), but there were no consistent changes in liver iron. Tissue levels of
      selenium in brain and liver were similar for the control and AN treatment groups.
      AN induces significant and differential changes in the levels of zinc, copper,
      and iron in brain and liver. These changes likely play a pivotal role in
      mediating AN toxicity, most likely via changes in cellular redox status.

PMID- 19165427
TI  - Trends in influenza vaccination coverage rates in Germany over six seasons from
      2001/02 to 2006/07.
AB  - BACKGROUND AND PURPOSE: Influenza is a considerable health problem all over the
      world. Vaccination is the most important measure for preventing influenza and
      reducing morbidity and mortality. The aims of this study were to assess influenza
      vaccination coverage from 2001 to 2007 in Germany, to understand motivations and
      barriers to vaccination, and to identify vaccination intentions for season
      2007/08. METHODS: In representative household surveys, 12,039 telephone
      interviews with individuals aged >or= 14 years were conducted between 2001 and
      2007. Essentially the same questionnaire was used in all seasons. RESULTS: In
      season 2006/07, the overall influenza vaccination coverage rate dropped from
      32.5% in the previous season to 27.4%. In the elderly (>or= 60 years), the rate
      decreased from 51.6% to 44.7% and the odds ratio of being vaccinated, compared to
      those not belonging to a high-risk group, remained < 5. Chronically ill elderly
      persons had an odds ratio of vaccination of 7, while younger chronically ill
      persons and health-care workers had odds ratios of about 2. Perceiving influenza
      as a serious illness was the most frequent reason for getting vaccinated. 14% of
      those vaccinated in 2006/07 indicated the threat of avian flu as a reason. The
      main reason for not getting vaccinated was thinking not to be likely to catch the
      flu. A recommendation by the family doctor/nurse was perceived as the major
      encouraging factor for vaccination. A total of 44.7% of the respondents intended
      to get vaccinated against influenza in 2007/08. CONCLUSION: A trend of increasing
      vaccination rates was observed from 2001 to 2006 in Germany, but the rates dipped
      by almost a sixth after 2005/06. The loss of media interest in the threat of
      avian influenza after February 2006 and stalling reimbursement programs may have
      contributed to the recent drop in vaccination rates.

PMID- 19165428
TI  - [Spectrum of tuberculous diseases in a pulmonary outpatient clinic].
AB  - BACKGROUND: Although the incidence of 6.6 newly diagnosed tuberculosis (TB) cases
      per 100,000 inhabitants is in decline in Germany, TB remains a disease of
      significant epidemiologic importance. PATIENTS AND METHODS: From 04/2001 to
      07/2008, a total of 75 TB patients of an internal-pulmonary outpatient clinic had
      been treated (0.5% of all patients). 58 (77.3%) patients fulfilled the criteria
      of an active TB, 17 (22.7%) of latent tuberculous infection (LTBI). 68.0% were
      male (average age men 39.3 +/- 16.9 years [mean +/- standard deviation], women
      46.8 +/- 21.5 years; p = not significant). 69.3% of the patients were born in
      Germany, 30.7% abroad. 84.5% patients had isolated pulmonary, 8.6% additional
      organ involvement, and 6.9% isolated extrapulmonary TB. 62.1% of active TB cases
      were microbiologically proven (51.7% microscopically, 43.1% in addition
      culturally, 6.9% exclusively culturally, 19.0% by polymerase chain reaction
      [PCR]). RESULTS: Of 23 tests, 52.2% were fully sensitive against the most
      important first-line drugs ethambutol (M), isoniazid (H), rifampicin (R),
      pyrazinamide (Z), und streptomycin (S). 13.0% had an isolated resistance against
      H (4.4%) or S (8.6%), 4.4% a multiple drug resistance (MDR) against R und H,
      30.4% a polyresistance (S and H). Symptoms were quite often unspecific, not taken
      care of, or misinterpreted. CONCLUSION: Diagnosis and therapy of an active or
      latent TB illness remains, an important task and challenge, necessitating an
      effective cooperation of outpatient, hospital, and health authority institutions.

PMID- 19165431
TI  - [Who may make diagnoses].

PMID- 19165429
TI  - [Incremental cost-effectiveness of dipyridamole + acetylsalicylic acid in
      secondary prevention of ischemic noncardioembolic stroke].
AB  - BACKGROUND AND PURPOSE: The aim of secondary prevention in stroke is to avoid
      restrokes. The current standard treatment in Germany is a lifelong therapy with
      low-dose acetylsalicylic acid (ASA). As the incidence of restrokes remains
      relatively high from a health-care payer's perspective, the question arises,
      whether the combination of dipyridamole + acetylsalicylic acid (Dip + ASA) is
      cost-effective in comparison with a therapy based on ASA only. METHODS: A
      decision-analytic cross-sectional epidemiologic steady-state model of the German
      population compares the effects of two strategies of secondary prevention with
      Dip + ASA (12 months vs. open end) and with ASA monotherapy. RESULTS: The model
      predicts the following estimates: the annual incidence of initial ischemic
      strokes in Germany is estimated at 130,000 plus an extra 34,000 restrokes (base
      year 2005). Additionally, there are 580,000 people that experienced a stroke > 12
      months earlier, of whom 135,000 had a restroke. Every year, nearly 89,000 Germans
      die of the consequences of an ischemic stroke. If Dip + ASA would have been the
      standard therapy in secondary prevention of ischemic stroke, an additional 7,500
      persons could have been saved in 2005. Statutory health insurance would have to
      spend 33,000 Euro for every additional life year gained with Dip + ASA as
      secondary prevention strategy. If secondary prevention with Dip + ASA would be
      limited to the first 12 months after an initial stroke, which is the time of the
      highest risk for a restroke, the incremental cost-effectiveness ratio is about
      7,000 Euro per life year gained. The results proved to be robust in sensitivity
      analyses. CONCLUSION: Secondary prevention with Dip + ASA is cost-effective in
      comparison to treatment with ASA in monotherapy, because its incremental cost
      effectiveness ratio is within common ranges of social willingness to pay. From
      the standpoint of the patient as well as the health-care payer, focusing on the
      first 12 months after the initial incident for intensified preventive drug
      treatment with Dip + ASA should be valuable from a medical as well as a health
      economic perspective.

PMID- 19165430
TI  - [Current strategies in the treatment of atrial fibrillation].

PMID- 19165432
TI  - [Superficial cerebral hemosiderosis].

PMID- 19165433
TI  - [To the speech made by Dr. Annette Schavan, Minister of Education and Research,
      at the 114th Congress of the German Society of Internal Medicine].

PMID- 19165434
TI  - [Speech made by Dr. Annette Schavan, Minister of Education and Research, member
      of the Bundestag, at the opening of the congress of the German Society of
      Internal Medicine in Wiesbaden, March 30, 2008].

PMID- 19165436
TI  - Evaluation of the clinical efficacy of conservative treatment in the management
      of carpal tunnel syndrome.
AB  - INTRODUCTION: Carpal tunnel syndrome (CTS) is impingement of the median nerve at
      the wrist. The aim of this study was to compare the effectiveness of tendon and
      nerve gliding exercises with standard conservative treatment (SCT), which
      consists of splinting and local steroid injections, in the treatment of CTS.
      METHODS: This study was a prospective, randomized, single-blind trial. Patients
      were randomized into three groups: treatment with SCT (Group 1); SCT and tendon
      and nerve gliding exercises (Group 2); tendon and nerve gliding exercises only
      (Group 3). A symptom total point score was obtained from five symptoms: hand
      pain, tingling, numbness, nocturnal numbness, and interrupted sleep. The
      functional status of the hand was determined by assessing seven daily living
      activities: writing, buttoning clothes, gripping a telephone receiver, opening
      jars, doing housework, carrying grocery bags, and bathing. Standard physical
      examinations (Tinel's test, Phalen's test, reverse Phalen's test, and the
      compression test) were also performed. RESULTS: A total of 111 patients who were
      diagnosed with intermediate-stage CTS were included in the study. At the end of
      treatment, significant improvements in symptoms and functionality were detected
      in all groups. However, the recovery of patients in Groups 1 (n=41) and 2 (n=35)
      were found to be significantly greater than that of patients in Group 3 (n=35;
      P<0.001). Patient satisfaction was investigated a mean of 11 months after
      treatment. Percentages of asymptomatic patients in Group 1 and Group 2 were
      significantly higher than in Group 3 (P=0.02 and P=0.04, respectively).
      CONCLUSION: In the intermediate stage of CTS, SCT was an effective treatment to
      improve symptoms and functional status. Tendon and nerve gliding exercises alone
      were inferior to either SCT alone or SCT in combination with gliding exercises.

PMID- 19165437
TI  - Ivabradine: beyond heart rate control.
AB  - Chronic stable angina pectoris (CSAP) usually occurs in patients with coronary
      artery disease (CAD) that affects one or more large epicardial arteries. It
      results when myocardial perfusion is insufficient to meet cardiac metabolic
      demand. Elevated heart rate (HR) is an important factor in the development of
      myocardial ischemia and angina pectoris. The pharmacologic agents most commonly
      administered in the treatment of CSAP are beta-blockers and calcium channel
      blockers (CCBs). However, the use of beta-blockers is limited by poor compliance
      related to contraindications and comorbidities, especially in elderly patients.
      Ivabradine is a new selective HR-lowering agent that selectively inhibits the
      pacemaker current I (f) in the sinus atrial node. In several randomized
      controlled trials, ivabradine 5-10 mg twice daily has demonstrated equivalent
      anti-ischemic and anti-anginal activity to beta-blockers and CCBs, with a good
      safety and tolerability profile. Although ivabradine has been shown not to
      improve cardiac outcomes in patients with stable CAD and left ventricular
      systolic dysfunction, it may be used to reduce the incidence of CAD outcomes in a
      subgroup of patients with HR > or =70 bpm. The aim of this short review is to
      summarize the use of ivabradine in the treatment of CSAP, and its potential
      utility in atherosclerosis, primitive and dilatative cardiomyopathy, and
      arrhythmias, such as postural tachycardia syndrome and inappropriate sinus
      tachycardia, where exclusive lowering of elevated HR may prove beneficial.

PMID- 19165439
TI  - ["The goal is a man's image of respect" training palliative care in Austria--the
      2(nd) intensive course of palliative medicine].

PMID- 19165438
TI  - Can the viral reservoir of latently infected CD4(+) T cells be eradicated with
      antiretroviral HIV drugs?
AB  - The majority of cells infected with the human immunodeficiency virus are
      activated CD4(+) T cells, which can be treated with antiretoviral drugs. However,
      an obstacle to eradication is the presence of viral reservoirs, such as latently
      infected CD4(+) T cells. Such cells may be less susceptible to antiretroviral
      drugs and may persist at low levels during treatment. We introduce a model of
      impulsive differential equations that describe T cell and drug interactions. We
      make the extreme assumption that latently infected cells are unaffected by drugs,
      in order to answer the research question: Can the viral reservoir of latently
      infected cells be eradicated using current antiretroviral therapy? We analyse the
      model in both the presence and absence of drugs, showing that, if the frequency
      of drug taking is sufficiently high, then the number of uninfected CD4(+) T cells
      approaches the number of T cells in the uninfected immune system. In particular,
      this implies that the latent reservoir will be eliminated. It follows that, with
      sufficient application of drugs, latently infected cells cannot sustain a viral
      reservoir on their own. We illustrate the results with numerical simulations.

PMID- 19165440
TI  - [Paternalism and autonomy--no contradiction].
AB  - Patient autonomy became increasingly important during the last decades. It is
      often described to be an antagonist to medical paternalism. Like for patients
      with full decisional capacity, autonomy should also be protected for
      incapacitated patients. To enable this, the Austrian legislator recently
      regulated advance directives and durable powers of attorney. These tools should
      be combined with a process of communication with the patient's loved ones and
      consultation by a caring physician according to the integrative model. This can
      enhance and supplement the patient's autonomy. This article demonstrates
      surrogate decision making in theory and by the example of a case report.

PMID- 19165441
TI  - [The difficult patient--a medical viewpoint].
AB  - The management of patients suffering from chronic incurable organic disease
      combined with a strong element of psychiatric disorder requires patience.
      Sometimes the involved physicians reach their limits and are pushed to the brink
      of resignation.

PMID- 19165442
TI  - [Limitation of medical treatment and ethics in chronic recurrent Clivus
      chordoma].
AB  - In this paper ethical questions concerning the limitation and termination of
      medical treatment of comatose patients will be discussed on the basis of a case
      study. The team is confronted with extremely high communicative and ethical
      demands, since every person engaged in the treatment and care of the patient
      should take part in this decision making process. The final responsibility
      regarding the medical decisions, however, lies with the doctor in charge. In such
      cases advance directives or living wills are important and should be taken into
      consideration.

PMID- 19165443
TI  - [Palliative sedation in pediatric oncology].
AB  - Severe pain caused by multiple metastases in bones in a pediatric patient
      suffering from rhabdomyosarcoma, a solid tumor of childhood, made palliative
      sedation therapy after developing metastases in lung necessary. The premises for
      this therapy, the difference in the choice of drugs compared to adults and
      psychology of the dying child are discussed.

PMID- 19165444
TI  - [Difficult communication with next-of-kin].
AB  - Looking back on the case report of Mr. B. and his spouse as well as on the way
      our team cared for both of them, it becomes clear how strong the pressure upon
      family members is and how important professional support is. Relatives have an
      enormous need for attendance, although this is often not evident for them.
      Optimal support of family members helps to reduce their uncertainties and fears
      and to improve patients' quality of life. Empathic and professional behaviour is
      meant to allow relatives to take leave of their family members in a satisfactory
      manner.

PMID- 19165446
TI  - [Hypnosis as an alternative treatment for pain in palliative medicine].
AB  - Pain--which can have a variety of causes--constitutes a severe problem for
      patients in need of palliative care, because this pain usually dramatically
      impairs their quality of life. Thus, the more advanced a terminal illness has
      become, the more hospital staff should focus on holistic treatment, encompassing
      body, mind and soul of the patient. Apart from conventional medication-based pain
      therapy, there is also a variety of non-medicinal treatments for pain. One of
      these methods is hypnosis, an imaginative treatment that activates available
      resources; it is not only an effective way of alleviating pain, but it also can
      ease psychological problems at the same time.

PMID- 19165445
TI  - [Cannabinoids in medicine].
AB  - Cannabinoids have been known for many centuries because of their various effects
      in healthcare. They are primarily effective in reducing nausea, vomiting, pain,
      anorexia, spasticity and depression. Some other effects are known, all seem to be
      mediated by cannabinoid receptors in the central nervous system. In the past
      years, medical use has been proven in several studies. Today, the therapeutical
      use of cannabinoids in medicine is increasing, and access was made easier.
      Especially in pain-management and palliative care, they seem to be a valuable
      therapeutic option.

PMID- 19165447
TI  - [Dyspnoea--a multifactorial and multidimensional symptom].
AB  - The treatment of dyspnoea is a considerable challenge in palliative care.
      Respiratory problems, besides pain, belong to the most common symptoms of
      terminally ill patients. Invasiveness of diagnostic measures and treatment
      options demand a critical evaluation of the patient's burden and the expected
      relief by the therapy. On the basis of a case study of a lung cancer patient, the
      complexity of different causes of dyspnoea will be discussed. Special
      consideration will be taken to the psychosocial dimension of dyspnoea.

PMID- 19165448
TI  - [Methods of symptom control in malignant ascites].
AB  - Ascites remains a challenge in many patients with advanced cancers in palliative
      care. Although paracentesis, diuretics and shunting are the commonly used
      procedures, the evidence is weak. A fast but temporary effect is achieved on
      symptom relief by paracentesis. Some inherent risks have to be taken into
      account. On the basis of a case report, different attempts to control malignant
      ascites are discussed. The report of a young woman with relapsing ovarian cancer
      and recurrent ascites is presented including the management of symptomatic
      malignant ascites.

PMID- 19165449
TI  - [Secondary malignant lymphedema in head and neck tumors].
AB  - The occurrence of edema is a serious problem of patients suffering from cancer
      and may have various causes. Particularly, the secondary malignant lymphedema
      poses a special threat to patients. In some cases, it indicates the progression
      of illness, and in fact also results in mutilating physical changes, which add to
      the already existing impairments caused by the cancer disease. So far therapeutic
      interventions are limited. Current management consists of physical therapy and
      pharmacological interventions. There are few powerful studies concerning the
      efficiency and hardly any concerning combined or comparative treatment in the
      literature. Most of them focus on the management of lymphedema in breast cancer
      patients. Preventive measures and supportive therapy are rarely being discussed.
      In this case report, we describe the successful use of Selen and Sandostatin in
      treating a facial edema of a patient with advanced head-neck cancer.

PMID- 19165450
TI  - [Bisphosphonates and osteonecrosis of the jaw--an increasing challenge in
      palliative care].
AB  - Bone metastases are one of the most common complications of cancer. Up to 70% of
      patients with advanced breast cancer metastasize to the bone. The standard long
      term treatment of bone metastases is bisphosphonates. This effective therapy,
      however, is able to cause serious side effects. Osteonecrosis of the jaw (ONJ) is
      a recently detected adverse outcome associated in rare cases with bisphosphonate
      therapy.

PMID- 19165451
TI  - [Delirium in a patient with cerebral metastasis].
AB  - Delirium is a common complication in palliative care of preterminally or
      terminally ill cancer patients. Based on a case report of a delirious male
      patient with cerebral metastasis, typical manifestations, etiologies, risk
      factors and possible therapies of palliative delirium will be reviewed.
      Furthermore, difficult therapeutic decisions with regard to the use of
      corticosteroids, fentanyl and parenteral rehydration therapy will be discussed.

PMID- 19165452
TI  - [Treatment of breast cancer in elderly patients].
AB  - Invasive therapeutic procedures in elderly patients with advanced breast cancer
      are usually contraindicated as improvement of the quality of life in this
      situation is considered more important than increasing life span. In the present
      case, however, surgical removal of the tumour has led to a significant
      improvement of the quality of life and could have been even more beneficial if
      carried out at an earlier stage.

PMID- 19165453
TI  - [Primary central nervous system lymphoma in elderly patients--a therapeutical
      challenge].
AB  - The importance of whole brain radiotherapy in elderly patients with primary
      central nervous system lymphoma (PCNSL) and other therapeutic options are
      discussed on the basis of a case study.

PMID- 19165454
TI  - [Palliative care in patients with head and neck cancer].
AB  - Progressive cancer leads to loss of quality of life. This is particularly true
      for head and neck cancers as they dramatically affect the patients and in
      addition to this psychological burden cause a lot of physical disabilities.
      Patients struggle against retreat and helplessness of their environment, feel
      ostracized and not any longer being a human. In advanced diseases, surgery is not
      the first choice of treatment. Ostensible control of symptoms, care of relatives
      and notice of psychosocial facts are the most important therapeutic issues in
      these patients. They gain the greatest benefit from palliative care with good
      control of symptoms. This is highlighted by the following case reports.

PMID- 19165455
TI  - [Palliative therapy in bronchial carcinoma--implanted delivery system and ports].
AB  - This case report of a 54-year-old patient, with a metastasized non-small cell
      bronchial carcinoma, shows us the different ways in pain therapy alternatives. We
      report the possibility of using spinal delivery systems (especially
      epidural/intrathecal) in palliative therapy, if like in this case oral applicated
      opioids were not very successful. We discuss the advantages and disadvantages of
      this method and point out the possible side effects. Finally, we conclude that it
      has to be decided on a case per case basis, if this therapy is applicable or not.

PMID- 19165456
TI  - [Malignant melanoma--local treatment of ulcers and necrotic wounds].
AB  - The management of chronic wounds is a challenge for the medical and nursing team.
      The necrotic tissue should be removed mechanically, beginning with water or
      normal saline. In some cases medical fly larvae can be useful in this situation.
      Modern wound antiseptics are much easier and hygienic in their handling. The
      reduction of unpleasant odor places an important role in the quality of life.
      Generally, the patients' preferences in the variety of methods to treat
      problematic wound odor should be taken into consideration.

PMID- 19165457
TI  - [Palliative care in the management of heart failure].
AB  - Heart failure is an increasingly prevalent, often progressive condition
      associated with high morbidity and mortality. In end-stage heart failure a
      strategy is urgently needed to ensure a truly progressive move away from invasive
      treatment toward supportive terminal care. The basic principles of palliative
      care--good communication and close attention to symptom control--should be
      adopted to improve the quality of life of heart failure patients. On the basis of
      a case study, the need of palliative care in the management of heart failure will
      be demonstrated.

PMID- 19165458
TI  - [In memory of Helmut Wyklicky].

PMID- 19165459
TI  - [The Taylor spatial frame fixator. Soft-tissue distraction for post-traumatic
      varus deformities of the hindfoot].
AB  - Despite adequate primary treatment many ankle fractures result in post-traumatic
      deformities and arthrosis. Revision mostly requires a multidirectional correction
      whereas internal fixation procedures are often not applicable due to soft tissue
      damage and the extent of deformity. The Taylor spatial frame enables simultaneous
      correction of multidirectional deformities through a virtual hinge using the same
      ideas of distraction osteogenesis as the Ilizarov fixator. The presented case
      demonstrates minimally invasive correction of a complex deformity of the ankle
      with the Taylor spatial frame fixator. Orthogonal alignment was achieved and a
      stabilizing tibiotalar arthrodesis was performed achieving a good functional and
      pain-free result.

PMID- 19165460
TI  - [Theory of cognition and natural philosophy in neurology. The principle of
      localization in the debate between Viktor von Weizsacker, Kurt Goldstein, and
      Otfrid Foerster in 1930].
AB  - Restitution after brain damage was the leading topic in 1930 at the 20th annual
      meeting of the Society of German Neurologists in Dresden, Germany. One of the
      "nonanatomic" presentations was held by Viktor von Weizsacker about modifications
      in neurological function. Finally the presentation by Kurt Goldstein about
      restitution after damage of the brain cortex, strongly supported by Weizsacker,
      was the starting point for controversies on the significance of natural
      scientific methods in the field of neurology. Goldstein and Weizsacker favored
      the idea that function can be understood only if we consider it in light of the
      whole organism. However, the president of the Society of German Neurologists,
      Otfrid Foerster, was mainly influenced by the overall concept of the structure of
      the peripheral nervous system and - as Weizsacker indirectly blamed - came to
      inadequate conclusions by transferring these concepts to the entire nervous
      system. In contrast Weizsacker and Goldstein suggested analyzing pathological
      phenomena not only according to classical physiology, i.e. isolated data acquired
      by the dissecting method of natural science. Weizsacker stressed hermeneutic
      views concerning the mind: body relationship in a phenomenologically oriented
      medical anthropology. Some years later Foerster linked up with Weizsacker's
      position. Goldstein established the new method, the so-called holistic,
      organismic approach, which he carried on after emigrating to the U.S.A. in 1935.
      The Heidelberg School around Weizsacker tried during the following years to
      liberate neurology from the ideology of materialistic reductionism without
      however reducing it to simple psychology. The doctrine of neurons and principles
      of saltatory conduction as basic and descriptive instruments in neurology were
      not to be questioned. In 1941 Weizsacker succeeded Foerster as Professor of
      Neurology at the University of Breslau and Director of the Neurological Research
      Institute. His literary work "The Circle of Form. Theory of the Unity of Movement
      and Perception" and Goldstein's "The Organism. A Holistic Approach to Biology
      derived from Pathological Data in Man" [new edn. by Oliver Sacks, Zone Books, New
      York, 1995] obtained paradigm values which had their beginnings in Dresden in
      1930. "The crisis in biology in the matter of theory of cognition and natural
      philosophy" was already then obvious and still can be found in present discussion
      about the relationship between neurosciences and humanities. Weizsacker increased
      his focus on medical anthropology by taking a full professorship of general
      clinical medicine in 1946 in Heidelberg. It is not without reason that Weizsacker
      is recognized as a founder of psychosomatic medicine.

PMID- 19165462
TI  - Costs of intermittent measurement of central venous oxygen saturations by blood
      gas analysis.

PMID- 19165461
TI  - Cluster analysis of rat pancreatic islet gene mRNA levels after culture in low-,
      intermediate- and high-glucose concentrations.
AB  - AIMS/HYPOTHESIS: Survival and function of insulin-secreting pancreatic beta cells
      are markedly altered by changes in nutrient availability. In vitro, culture in 10
      rather than 2 mmol/l glucose improves rodent beta cell survival and function,
      whereas glucose concentrations above 10 mmol/l are deleterious. METHODS: To
      identify the mechanisms of such beta cell plasticity, we tested the effects of 18
      h culture at 2, 5, 10 and 30 mmol/l glucose on the transcriptome of rat islets
      pre-cultured for 1 week at 10 mmol/l glucose using Affymetrix Rat 230 2.0 arrays.
      RESULTS: Culture in either 2-5 or 30 mmol/l instead of 10 mmol/l glucose markedly
      impaired beta cell function, while little affecting cell survival. Of about
      16,000 probe-sets reliably detected in islets, some 5,000 were significantly up-
      or downregulated at least 1.4-fold by glucose. Analysis of these probe-sets with
      GeneCluster software identified ten mRNA profiles with unidirectional up- or
      downregulation between 2 and 10, 2 and 30, 5 and 10, 5 and 30 or 10 and 30 mmol/l
      glucose. It also identified eight complex V-shaped or inverse V-shaped profiles
      with a nadir or peak level of expression in 5 or 10 mmol/l glucose. Analysis of
      genes belonging to these various clusters using Onto-express and GenMAPP software
      revealed several signalling and metabolic pathways that may contribute to
      induction of beta cell dysfunction and apoptosis after culture in low- or high-
      vs intermediate-glucose concentration. CONCLUSIONS/INTERPRETATION: We have
      identified 18 distinct mRNA profiles of glucose-induced changes in islet gene
      mRNA levels that should help understand the mechanisms by which glucose affects
      beta cell survival and function under states of chronic hypo- or hyperglycaemia.

PMID- 19165463
TI  - Sleep and delirium in ICU patients: a review of mechanisms and manifestations.
AB  - Sleep deprivation and delirium are conditions commonly encountered in intensive
      care unit patients. Sleep in these patients is characterized by sleep
      fragmentation, an increase in light sleep, and a decrease of both slow wave sleep
      and rapid eye movement sleep. The most common types of delirium in this
      population are hypoactive and mixed-type. Knowledge about the mechanisms of sleep
      and delirium has evolved over time, but these phenomena are not yet well
      understood. What is known, however, is that different areas in the brainstem
      transmit information to the thalamus and cortex necessary for sleep-wake
      regulation. Delirium is related to an imbalance in the synthesis, release, and
      inactivation of some neurotransmitters, particularly acetylcholine and dopamine.
      The relationship between sleep deprivation and delirium has been studied for many
      years and has been viewed as reciprocal. The link between them may be ascribed to
      shared mechanisms. An imbalance in neurotransmitters as well as alteration of
      melatonin production may contribute to the pathogenesis of both phenomena. A
      better understanding of the mechanisms and factors that contribute to sleep
      deprivation and delirium can guide the development of new methods and models for
      prevention and treatment of these problems and consequently improve patient
      outcomes.

PMID- 19165464
TI  - Depression in general intensive care unit survivors: a systematic review.
AB  - PURPOSE: To critically review data on the prevalence of depressive symptoms in
      general intensive care unit (ICU) survivors, risk factors for these symptoms, and
      their impact on health-related quality of life (HRQOL). METHODS: We conducted a
      systematic review using Medline, EMBASE, Cochrane Library, CINAHL, PsycINFO, and
      a hand-search of 13 journals. RESULTS: Fourteen studies were eligible. The median
      point prevalence of "clinically significant" depressive symptoms was 28% (total n
      = 1,213). Neither sex nor age were consistent risk factors for post-ICU
      depression, and severity of illness at ICU admission was consistently not a risk
      factor. Early post-ICU depressive symptoms were a strong risk factor for
      subsequent depressive symptoms. Post-ICU depressive symptoms were associated with
      substantially lower HRQOL. CONCLUSIONS: Depressive symptoms are common in general
      ICU survivors and negatively impact HRQOL. Future studies should address how
      factors related to individual patients, critical illness and post-ICU recovery
      are associated with depression in ICU survivors.

PMID- 19165465
TI  - Anatomic double-bundle ACL reconstruction: a call for indications.

PMID- 19165466
TI  - A mini-invasive adductor magnus tendon transfer technique for medial
      patellofemoral ligament reconstruction: a technical note.
AB  - Patellar dislocations are associated with injuries to the medial patellofemoral
      ligament (MPFL). Several techniques for MPFL reconstruction have been recently
      published with some disadvantages involved, including large skin incisions and
      donor site morbidity. Arthroscopic stabilizing techniques carry the potential of
      inadequate restoration of MPFL function. We present a minimally invasive
      technique for MPFL reconstruction using adductor magnus tendon autograft. This
      technique is easily performed, safe, and provides a stabilizing effect equal to
      current MPFL reconstructions. Skin incision of only 3-4 cm is located at the
      level of the proximal half of the patella. After identifying the distal insertion
      of the adductor magnus tendon, a tendon harvester is introduced to harvest the
      medial two-thirds of the tendon, while the distal insertion is left intact. The
      adductor magnus tendon is cut at 12-14 cm from its distal insertion and
      transferred into the patellar medial margin. Two suture anchors are inserted
      through the same incision at the superomedial aspect of the patella in the
      anatomic MPFL origin. The graft is tightened at 30 degrees knee flexion.
      Aftercare includes 4 weeks of brace treatment with restricted range of motion.

PMID- 19165467
TI  - Predicting anterior cruciate ligament integrity in patients with osteoarthritis.
AB  - This study looks at the difference between the macroscopic and microscopic
      appearances of the anterior cruciate ligament (ACL) in a sample of 55 consecutive
      patients admitted for routine total knee replacement for osteoarthritis. At the
      time of surgery the macroscopic appearance of the ACL was classified as normal,
      moderately damaged (fissured) or completely ruptured. The excised ACL was sent
      for histological examination and grading. The macroscopic appearance of the ACL
      at surgery was compared to the severity of disease on microscopic examination. At
      surgery, 31 ACLs were found to be macroscopically normal: 22 of these (71%)
      showed moderate to severe disease on microscopic assessment. Thus a
      macroscopically normal ACL does not necessarily imply histological integrity.
      This has clinical implications in other areas of knee surgery including
      Unicompartmental Knee Replacement which require a fully functional intact ACL.

PMID- 19165468
TI  - Clinical results and radiographical evaluation of opening wedge high tibial
      osteotomy for spontaneous osteonecrosis of the knee.
AB  - We evaluated the clinical outcomes, in terms of early weight bearing, of using
      opening wedge high tibial osteotomy (OWHTO) to treat spontaneous osteonecrosis of
      the medial femoral condyle of the knee (SONK) using TomoFix and artificial bone
      substitute. Damaged cartilage tissue was removed and drilling of the necrotic
      area followed by OWHTO was performed in 30 knees from 30 patients with an average
      age of 71 years (range 58-82) at the time of operation. Patients were allowed to
      undertake partial weight-bearing exercises 1 week after the osteotomy procedure,
      with all patients performing full weight-bearing exercise at 2 weeks post
      surgery. The mean follow-up period was 40 months (range 24-62). All of the SONK
      patients could walk with a full weight-bearing load, using only a T-cane, at 2
      weeks after undergoing OWHTO. Clinical assays, including the mean American Knee
      Society Score and Function Score, showed significant improvements from 51 to 93
      points, and 58 to 93 points, respectively. Prior to surgery, the average femoro
      tibial angle (FTA) during standing was 181 (1 degree anatomical varus) and had
      significantly changed to 170 (10 degrees valgus) at the time of follow-up. There
      were no cases of non-union, or implant failure in any of our patients. In
      addition, none of the patients could sit in the Japanese style prior to surgery,
      but 21 of 30 patients (70%) could do so after treatment. Arthroscopic findings
      could be observed in 24 out of 30 cases at implant removal. Necrotic area in each
      case was covered with fibrous cartilage-like tissue completely. Drilling of the
      necrotic area followed by OWHTO with TomoFix and artificial bone substitute is an
      effective treatment for SONK as it results in pain alleviation and regeneration
      of the fibrous cartilage tissue over the necrotic legion. In addition, an early
      weight-bearing exercise program is possible after this procedure and full weight
      bearing can be achieved at two weeks after surgery.

PMID- 19165469
TI  - Lactational coumestrol exposure increases ovarian apoptosis in adult rats.
AB  - This study is the first to examine the increased apoptosis in the adult rat ovary
      after lactational exposure to coumestrol (COU), a potent phytoestrogen. Lactating
      dams were gavaged at doses of 0.01, 0.1, 1, and 10 mg/kg COU during the lactation
      period and the reproductive effects of female pups were investigated in young
      adults. Rats were sacrificed at postnatal days (PND) 81-84. Ovarian weights were
      reduced significantly at 0.1 and 1.0 mg/kg COU. The reduction in the ovarian
      weight occurred in parallel with an increase in the apoptosis at PND 135-140. A
      marked dose-dependent increase in the expressions of active caspase-3 and -7 was
      observed in ovarian granulosa cells. Immunostaining for active caspase-3 and the
      TUNEL staining of apoptotic cells were also increased in ovaries exposed to COU
      in a dose-dependent manner. These results suggest new sights into the effect of
      lactational exposure to COU on the female reproductive health.

PMID- 19165470
TI  - Alterations in neurofilaments content and calpains activity of sciatic nerve of
      carbon disulfide-treated rats.
AB  - Chronic exposure to carbon disulfide (CS2) can induce polyneuropathy in
      occupational worker and experimental animals, but underlying mechanism for CS2
      neurotoxicity is currently unknown. In the present study, male Wistar rats were
      randomly divided into two experimental groups and one control group. The rats in
      two experimental groups were treated with CS2 by gavage at dosages of 300 and 500
      mg/kg per day, respectively, five times per week for 12 weeks. The contents of
      neurofilament triplet proteins (NF-H, NF-M, NF-L) and two calpain isoforms (m
      calpain and u-calpain) in sciatic nerves were determined by immunoblotting. In
      the meantime, the mRNA levels of NF-H, NF-M and NF-L in spinal cords were
      quantified by reverse transcriptase-polymerase chain reaction, and the total
      activity of calpains in sciatic nerves was measured by fluorescence assay.
      Results showed that the contents of NF-M and NF-L in CS2-treated rats sciatic
      nerves increased significantly except NF-M in low dose group. The contents and
      activity of m-calpain and u-calpain in sciatic nerve also demonstrated a
      significant elevation. Furthermore, the levels of mRNA expression of NFH, NFM and
      NFL genes were up-regulated consistently in spinal cords of treated rats. These
      findings suggested that CS2 intoxication was associated with the disruption of
      neurofilaments homeostasis and activiation of calpains in rat sciatic nerves,
      which might be involved in the development of CS2-induced peripheral neuropathy.

PMID- 19165472
TI  - Diagnostic assays.

PMID- 19165471
TI  - Involvement of local serotonin-2A but not serotonin-1B receptors in the
      reinforcing effects of ethanol within the posterior ventral tegmental area of
      female Wistar rats.
AB  - RATIONALE: Previous studies indicated that ethanol could be self-infused into the
      posterior ventral tegmental area (p-VTA) and that activation of local serotonin-3
      (5-HT(3)) receptors was involved. 5-HT(1B) and 5-HT(2A) receptors are involved in
      the effects of 5-HT and ethanol on VTA dopamine neurons. OBJECTIVE: The current
      study used the intracranial self-administration (ICSA) procedure to determine the
      involvement of local 5-HT(1B) and 5-HT(2A) receptors in the self-infusion of
      ethanol into the p-VTA. MATERIALS AND METHODS: Female Wistar rats were implanted
      unilaterally with a guide cannula aimed at the p-VTA. Seven days after surgery,
      rats were placed into the two-lever operant conditioning chambers for ICSA tests.
      The tests consisted of four acquisition sessions with self-infusion of 200 mg%
      ethanol alone, two or three sessions with co-infusion of the 5-HT(1B) antagonist
      GR 55562 (10, 100, or 200 microM) or the 5-HT(2A) antagonist R-96544 (10, 100, or
      200 microM) with 200 mg% ethanol, and one final session with 200 mg% ethanol
      alone. RESULTS: During the acquisition sessions, all rats readily self-infused
      ethanol and discriminated the active from inactive lever. Co-infusion of GR
      55562, at all three doses, had no effect on the self-infusion of ethanol. In
      contrast, co-infusion of R-96544, at the two higher doses, attenuated responding
      on the active lever for ethanol infusion (p < 0.05). CONCLUSION: The results
      suggest that the reinforcing effects of ethanol within the p-VTA are modulated,
      at least in part, by activation of local 5-HT(2A), but not 5-HT(1B), receptors.

PMID- 19165473
TI  - Association of right-to-left shunt with frontal white matter lesions in T2
      weighted MR imaging of stroke patients.
AB  - INTRODUCTION: Cardiac right-to-left shunt (RLS), mainly due to patent foramen
      ovale (PFO), is a risk factor for paradoxical embolism and stroke. Results of
      studies about brain lesions in diffusion-weighted imaging (DWI) in PFO patients
      were controversial. DWI only detects acute ischemic lesions. We assessed the
      hypothesis that, in T2-weighted magnetic resonance imaging (T2WI) of stroke
      patients, RLS is associated with a typical distribution of small white matter
      lesions. MATERIALS AND METHODS: In this retrospective case-control study, T2WI
      images of 162 stroke patients were evaluated. From stroke patients admitted
      between 1999 and 2003, 81 stroke patients with RLS were identified with contrast
      enhanced transcranial Doppler (bubble test). Controls were 81 age-matched stroke
      patients without RLS (negative bubble test). In T2WI images, small lesions (<2
      cm) were categorized depending on their location in subcortical white matter,
      peritrigonal white matter, deep and paraventricular white matter, and basal
      ganglia. Additionally, larger territorial infarcts were rated. RESULTS: In T2WI
      frontal or predominantly frontal-located subcortical small white matter, lesions
      are significantly associated with RLS (p < 0.0001, chi-square test). Forty-three
      patients with RLS (53%) and only 19 control patients (23%) showed this frontal
      dominance. Odds ratio is 3.7 (95% confidence interval = 1.9-7.1) for having a RLS
      when T2WI shows this lesion pattern in a stroke patient. No patient of the RLS
      group and 6% of the control group had parietal dominance. Distribution of small
      lesions in other locations like basal ganglia or deep white matter showed no
      significant difference for the groups. CONCLUSION: A distribution of mainly
      frontal subcortical small white matter lesions in T2WI is significantly
      associated with RLS in stroke patients.

PMID- 19165474
TI  - Diffusion-weighted MR imaging of thyroid nodules.
AB  - INTRODUCTION: The purpose of our study was to determine the diagnostic role of
      diffusion-weighted imaging (DWI) in the differentiating of malignant and benign
      thyroid nodules by using fine needle aspiration biopsy cytology criteria as a
      reference standard. The apparent diffusion coefficient (ADC) values of the normal
      looking thyroid parenchyma were also evaluated both in normal patients and in
      patients with nodules. METHODS: Between March 2007 and February 2008, 76
      consecutive patients with ultrasound-diagnosed thyroid nodules and 20 healthy
      subjects underwent diffusion-weighted MR imaging by using single-shot spin echo,
      echo planar imaging. A total of 93 nodules were included in the study using the
      following b factors 100, 200, and 300 mm(2)/s. ADC values of thyroid nodules and
      normal area in all subjects were calculated and compared using suitable
      statistical analysis. RESULTS: Mean ADC values for malignant and benign nodules
      were 0.96+/-0.65 x 10(-3) and 3.06+/-0.71 x 10(-3)mm(2)/s for b-100 factor,
      0.56+/-0.43 x 10(-3) and 1.80+/-0.60 x 10(-3)mm(2)/s for b-200, and 0.30+/-0.20 x
      10(-3) and 1.15+/-0.43 x 10(-3)mm(2)/s, for b-300, respectively. Mean ADC values
      of malignant nodules were lower than benign nodules. There were significant
      differences in ADC values between benign and malignant nodules. ADC values among
      normal-appearing thyroid parenchyma of patients and normal-appearing thyroid
      parenchyma of healthy subjects were insignificant at all b factors. CONCLUSION:
      Benign nodules have higher ADC values than malignant ones. DWI may be helpful in
      differentiating malign and benign thyroid nodules.

PMID- 19165475
TI  - The pathophysiology does not denote the mechanism.

PMID- 19165476
TI  - Unraveling the puzzle.

PMID- 19165477
TI  - Protein-losing enteropathy detected by Tc-99m-MDP scintigraphy.

PMID- 19165478
TI  - Severe bilateral renal injuries.

PMID- 19165479
TI  - Anatomy and development of the meninges: implications for subdural collections
      and CSF circulation.
AB  - The dura is traditionally viewed as a supportive fibrous covering of the brain
      containing the dural venous sinuses but otherwise devoid of vessels and lacking
      any specific function. However, review of the embryology and anatomy reveals the
      dura to be a complex, vascularized and innervated structure, not a simple fibrous
      covering. The dura contains an inner vascular plexus that is larger in the infant
      than in the adult, and this plexus likely plays a role in CSF absorption. This
      role could be particularly important in the infant whose arachnoid granulations
      are not completely developed. Although subdural hemorrhage is frequently
      traumatic, there are nontraumatic conditions associated with subdural hemorrhage,
      and the inner dural plexus is a likely source of bleeding in these nontraumatic
      circumstances. This review outlines the development and age-specific vascularity
      of the dura and offers an alternative perspective on the role of the dura in
      homeostasis of the central nervous system.

PMID- 19165480
TI  - Response to cytosolic nickel of Slow Vacuolar channels in the hyperaccumulator
      plant Alyssum bertolonii.
AB  - We applied the patch-clamp technique to investigate the transport properties of
      the Slow Vacuolar (SV) channel identified in leaf vacuoles of Alyssum bertolonii
      Desv., a nickel hyperaccumulator plant growing in serpentine soil of the northern
      Apennines (Italy). SV currents recorded in vacuoles from adult plants collected
      in their natural habitat showed high sensitivity towards cytosolic nickel. Dose
      response analyses indicated half-maximal current inhibition at submicromolar
      concentrations, i.e. up to three orders of magnitude lower than previously
      reported values from other plant species. The voltage-dependent increase of
      residual currents at saturating nickel concentrations could be interpreted as
      relief of channel block by nickel permeation at high positive membrane
      potentials. Including young plants of A. bertolonii into the study, we found that
      SV channels from these plants did not display elevated nickel sensitivity. This
      difference may be related to age-dependent changes in nickel hyperaccumulation of
      A. bertolonii leaf cells.

PMID- 19165482
TI  - Organ-specific hemosiderosis and functional correlation in Chinese patients with
      thalassemia intermedia and hemoglobin H disease.
AB  - We performed MRI assessment in 37 adult Chinese patients with thalassemia
      intermedia and hemoglobin H disease. Despite abnormal ferritin and liver T2*,
      only 5% of patients had cardiac hemosiderosis. The two patients with reduced
      ejection fraction had normal cardiac T2*. Half of the cases showed pituitary and
      pancreatic iron loading. Subclinical endocrine abnormalities (HOMA, insulin
      growth factor) showed correlation with pancreatic, pituitary, and cardiac MRI
      values. Prospective data with serial functional and imaging monitoring is needed
      to verify the utility for chelation to improve cardiac and endocrine function in
      this group of patients.

PMID- 19165483
TI  - Quantification of free total plasma DNA and minimal residual disease detection in
      the plasma of children with acute lymphoblastic leukemia.
AB  - The analysis of total plasma DNA and the monitoring of leukemic clone-specific
      immunoglobulin and/or T-cell receptor gene rearrangements for the evaluation of
      minimal residual disease (MRD) in the plasma may be useful tools for prognostic
      purposes or for early detection of subclinical disease recurrence in children
      with acute lymphoblastic leukemia (ALL). The aim of this paper is to establish
      reference ranges for total plasma DNA concentrations and to test the feasibility
      of MRD measurements employing plasma DNA from children with ALL by using real
      time quantitative (RQ)-PCR. Despite wide inter-individual variation, the median
      concentrations of total plasma DNA for 12 healthy donors (57 ng/ml), 21 children
      with ALL after day 4 of treatment initiation (62 ng/ml) and 13 children with
      other malignancies (76 ng/ml) were similar. However, ALL patients had
      significantly higher concentrations at diagnosis (277 ng/ml) and on treatment day
      3 (248 ng/ml) before returning to normal afterwards. Early plasma DNA MRD
      kinetics could be established for 15 ALL patients and showed good concordance
      with bone marrow MRD. Plasma DNA was higher in children with ALL at diagnosis but
      returned to normal within the first four treatment days. Despite low
      concentrations of DNA, it is feasible to measure MRD kinetics in plasma DNA
      during ALL induction therapy by adapted real-time PCR methodologies.

PMID- 19165484
TI  - Cellular and humoral immune alterations in thymectomized patients for thymoma.
AB  - The aim of this study was to analyze the impact of thymectomy on kinetics of the
      immune reconstitution in thymoma patients. Nine consecutive patients with
      completely resected thymoma were enrolled. Immunophenotype analysis (total
      lymphocytes, CD3, CD4, CD8, CD19, NK subsets) and detection of autoantibodies at
      6, 12, 18, and 24 months after thymectomy were planned. A prolonged inversion of
      CD4/CD8 ratio was present, due to a diminished number of CD4+ cells; CD8+ cell
      numbers remaining constantly normal at different time points; CD19+ cells
      remained for a long time understatement, achieving almost normal levels at 24
      months; and NK cells always showed a normal amount. Autoantibodies against the
      muscle acetylcholine receptor were detected in four patients (44.4%) at the time
      of diagnosis, while antinuclear antibody were detected in eight patients (88.8%)
      at different time points during postthymectomy. A high incidence of multiple
      primary neoplasms was observed (66.6% of cases). Our study showed that cellular
      and humoral immune alterations are a common sequelae of postthymectomy. Further
      studies, a longer surveillance and a cooperative approach, due to the rarity of
      the disease, are necessary to define eventual implications of immune alterations
      on patient's outcome.

PMID- 19165485
TI  - Interleukin-23 receptor (IL-23R) gene polymorphisms in acquired aplastic anemia.
AB  - Acquired aplastic anemia (AA) is a rare disease with a complex pathogenesis. In
      most cases, T cell-mediated immune destruction of hematopoietic cells results in
      peripheral blood pancytopenia and bone marrow hypoplasia. A subset of the
      heterodimeric interleukin-23 receptor gene (IL-23R) is significantly associated
      with autoimmune-mediated diseases. To examine whether IL-23R single nucleotide
      polymorphisms (SNPs) might contribute to AA, we selected three IL-23R SNPs with
      amino acid changes (rs11209026: p.Arg381Gln; rs41313262: p.Val362Ile; and
      rs11465797: p.Thr175Asn) and compared their frequencies in 279 AA patients and
      184 ethnically matched healthy controls. The three SNP prevalences were similar
      between the AA patients and controls. The Arg381Gln variant, which has a strong
      protective effect against inflammatory bowel disease, showed no association with
      AA. Furthermore, IL-23 levels in sera were measured in the AA patients and in
      controls, and there were no significant differences among them. Our results
      indicate that these three IL-23R SNPs and serum IL-23 level have no apparent
      impact on susceptibility to AA.

PMID- 19165486
TI  - [Flat epithelial atypia].
AB  - According to the WHO, flat epithelial atypia (FEA) is defined as a neoplastic
      epithelial proliferation of ductal type in either a single or in multiple
      terminal duct lobular unit(s) limited to the periphery of the ductules in a
      clinging growth pattern. The atypical cells may form between one and several
      layers of epithelial cells that show low grade cytologic atypia. FEA most often
      presents as mammographic microcalcifications, which are typically round
      (secretory type and psammomatous calcification in an eosinophilic matrix, so
      called ossifying calcifications). Clinical relevance is dependent on whether the
      lesion appears in isolation or whether it is an excision biopsy or a minimally
      invasive biopsy. Currently available data suggest that the risk of subsequent
      breast carcinoma in the ipsilateral breast is very low following the diagnosis of
      FEA. The differential diagnosis should include atypical ductal hyperplasia, low
      grade clinging ductal carcinoma in situ, blunt duct adenosis and apocrine
      metaplasia.

PMID- 19165487
TI  - [Limbal stem cell deficiency after chemical burns : investigations on the
      epithelial phenotype and inflammation status].
AB  - Limbal stem cell deficiency (LSCD) is clinically characterized by growth of
      fibrovascular pannus onto the corneal surface, chronic inflammation and impaired
      visual acuity. The aim of this study was to characterize the pannus tissue. Total
      RNA was isolated from six pannus samples and protein from three pannus samples
      from patients with LSCD caused by chemical burns. Normal human corneal tissue
      (n=6) and conjunctiva (n=6) were used as control tissues. The expression of the
      epithelial lineage markers keratin 3 (K3), K19 and MUC5AC, the inflammatory
      markers IL-1beta, ICAM-1 and VEGF was analyzed by Western Blotting and/or real
      time PCR. Normal corneal tissue had a higher expression of K3 and a lower
      expression of K19 and MUC5AC in comparison to normal conjunctiva. A higher
      expression of inflammatory markers was seen in conjunctiva compared to corneal
      tissue. The pannus tissue showed a similar expression of lineage markers to
      conjunctiva but a higher expression of most inflammatory markers as compared to
      both control tissues. The analyzed samples of pannus in LSCD resembled
      conjunctiva and not cornea and showed a high expression of inflammatory markers
      indicating chronic inflammation.

PMID- 19165489
TI  - 'Flatus tube enema' as an alternative to flexible sigmoidoscopy in reducing
      colonic volvulus and pseudo-obstruction: letter.

PMID- 19165490
TI  - Benefits of laparoscopic peritoneal lavage for complicated sigmoid
      diverticulitis.
AB  - BACKGROUND: The traditional therapy for perforated sigmoid diverticulitis with
      peritonitis is emergency colectomy usually with colostomy. We report laparoscopic
      exploration with peritoneal lavage as an alternative in seven patients who
      required emergency surgery for diverticulitis. METHODS: Six patients presented
      with diffuse peritonitis and one with a failure of percutaneous therapy. All
      patients were explored laparoscopically and the peritoneal cavity was lavaged
      with saline in addition to receiving intravenous antibiotics. Patient
      demographics, clinical response, length of stay, and complications were recorded.
      RESULTS: Six patients had resolution of peritonitis resolved and patients were
      discharged from the hospital. One of these patients who developed a pelvic
      abscess required a percutaneous drainage postoperatively. This patient ultimately
      returned 3 months later with recurrent symptoms and underwent colectomy with
      primary anastomosis. One patient failed to improve initially and underwent
      colectomy with primary anastomosis on the same admission. Five patients
      subsequently had elective sigmoid resections, four laparoscopic and one open.
      Mean length of stay was 7.7 days. There was no mortality. CONCLUSION: We conclude
      that laparoscopic exploration and peritoneal lavage can be performed safely in
      patients with diffuse, purulent peritonitis. Using this approach, most patients
      with purulent peritonitis can avoid emergent laparotomy with the risk of
      colostomy, and the need for a second surgery.

PMID- 19165491
TI  - Complications and reinterventions after surgery for obstructed defecation.
AB  - PURPOSE: Functional results following surgery for obstructed defecation (OD) have
      been widely investigated, but there are few reports aimed to analyze
      postoperative complications and re-interventions. This study investigates the
      adverse events requiring retreatment for obstructed defecation. METHODS: We
      retrospectively analyzed the records of 203 patients operated on by a single
      surgeon, 20 transabdominally and 183 transperineally (159 manual and 24 stapled).
      Postoperative complications requiring retreatment and outcome of reinterventions
      were analyzed. RESULTS: Adverse events requiring retreatment occurred in 14.3%
      more frequently after abdominal than after perineal procedures (20% vs. 13.7%),
      but the sample size of the two arms is different. Rectal bleeding and strictures
      were the most common adverse events (6.9%). Major complications, i.e., ischemic
      colitis requiring hemicolectomy and pelvic sepsis requiring colostomy also
      occurred (1%). The overall reintervention rate was 7.5%, (5% after abdominal and
      7.6% after perineal surgery). Overall, 59% of the reoperated patients were still
      constipated at a median follow up of 2 years. CONCLUSIONS: Complications
      requiring retreatment are not uncommon after surgery for OD and reinterventions
      are often unsuccessful. A careful preoperative evaluation and selection of
      patients should be undertaken in order to minimize adverse events.

PMID- 19165492
TI  - A case report of coronal fractures through the hamate, the capitate, and the
      trapezoid.
AB  - To our knowledge, the simultaneous coronal fractures of the hamate, capitate, and
      trapezoid have not been previously reported in the literature. There were few
      reports about coronal fractures of the hamate caused only by axial loading to the
      ulnar column. We report 43-year-old man who presented with painful swelling on
      the dorso-ulnar side of the wrist after striking a wall with his right clenched
      fist. The computed tomography scan demonstrated coronal fractures through the
      hamate, capitate, and trapezoid. We performed closed reduction and fixation with
      a percutaneous compression screw. At the last follow-up, the patient was able to
      return to sports activities without any symptoms.

PMID- 19165493
TI  - Overlapping dislocation of the pubic symphysis: report of three cases and review
      of the literature.
AB  - We present three cases of overlapping pubic symphysis dislocation and revise all
      the fully reported similar ones in the literature. The mechanism of injury,
      clinical presentation, radiographic assessment, associated injuries, management
      and complications of this uncommon injury are discussed.

PMID- 19165494
TI  - Functional outcomes of bilateral hip necrosis: total hip arthroplasty versus
      extracorporeal shockwave.
AB  - INTRODUCTION: This study compared the functional outcomes of total hip (THA) in
      one and shockwave (ESWT) in the other in 17 patients with bilateral hip necrosis.
      METHOD: In THA side, only one type of prosthesis was used and all components were
      press fixed. In ESWT side, each hip received 6,000 impulses of shockwave at 28
      kv. RESULTS: The evaluations included pain score and Harris hip score,
      radiographs and MR images. The magnitudes of improvement in pain and function
      favored the ESWT side. Thirteen patients rated ESWT better than THA; four
      patients reported comparable results between THA and ESWT, and none graded THA
      better than ESWT. Better functional outcomes were observed after ESWT for early
      hip necrosis than THA for late cases in patients with bilateral hip disease.

PMID- 19165496
TI  - Rac1 activates HIF-1 in retinal pigment epithelium cells under hypoxia.
AB  - BACKGROUND: Upregulation of vascular endothelial growth factor (VEGF) in hypoxic
      retinal pigment epithelium (RPE) cells, mediated by hypoxia-inducible factor-1
      (HIF-1) is responsible for choroidal neovascularization (CNV). HIF-1alpha is the
      inducible subunit of HIF-1, but the underlying mechanisms by which RPE cells
      sense a decrease in oxygen concentration and transduce this signal to HIF-1alpha
      are largely unknown. Rho family small GTPase Rac1, as a potential intermediate,
      possibly plays a pivotal role in activating HIF-1alpha in RPE cells under
      hypoxia. AIMS: To further define Rac1 playing an essential role in the induction
      of HIF-1alpha expression in RPE cells under hypoxia. METHODS: In this study, we
      examined the expression of HIF-1alpha and Rac1 in human RPE cells under hypoxia
      for 0, 1, 2, 4, 8, 12 and 24 h by RT-PCR and Western blot. To elucidate whether
      Rac1 is responsible for activating the expression of hypoxia-induced HIF-1alpha,
      human RPE cells were treated with Rac1 inhibitor NSC23766 under hypoxia for 0, 1,
      2, 4, 8, 12 and 24 h, and expression of HIF-1alpha and Rac1 measured by RT-PCR
      and Western blot. RESULTS: The mRNA expression of HIF-1alpha and Rac1 in RPE
      cells significantly increased in a time-dependent manner, reaching the maximum at
      4 h, and thereafter slowly declined. HIF-1alpha protein induction in human RPE
      cells was found after 1 h of hypoxia, reaching the maximum at 8 h, and then
      slowly declined. In response to hypoxia, the levels of Rac1 protein significantly
      increased, reaching the maximum at 4 h, and then slowly declined. After treatment
      with NSC23766, both HIF-1alpha and Rac1 expression were significantly inhibited
      in hypoxic RPE cells. CONCLUSIONS: Rac1 is crucial to activate HIF-1 in RPE cells
      under hypoxia, which may be a novel target other than VEGF and HIF-1 in
      developing CNV inhibitors.

PMID- 19165497
TI  - No relevant difference in quality of life and functional outcome at 12 months'
      follow-up-a randomised controlled trial comparing robot-assisted versus
      conventional laparoscopic Nissen fundoplication.
AB  - PURPOSE: The present randomised pilot trial was designed to compare robot
      assisted (RALF) and conventional laparoscopic fundoplication (CLF) focussing on
      post-operative quality of life (QOL) and functional outcome. Any long-lasting
      advantages for patients in this regard could be a justification for the use of
      RALF for the treatment of gastroesophageal reflux disease (GERD). METHODS: Forty
      patients with GERD were randomised to either RALF or to CLF. During a follow-up
      period of 12 months, patients' QOL and functional outcome were investigated using
      disease-specific questionnaires. RESULTS: There were no significant differences
      in the mean QOL (1.3 versus 1.1; P = 0.374) and functional outcome (1.27 versus
      1.3; P = 0.913) between both groups. Minor side effects such as bloating and
      persistent diarrhoea were present in four patients of each group. CONCLUSION: The
      present study did not show any benefit for RALF over CLF regarding QOL and
      functional outcome at 12 months' follow-up.

PMID- 19165499
TI  - Adenosine receptors in COPD and asymptomatic smokers: effects of smoking
      cessation.
AB  - Our group has shown that 1-year smoking cessation persisted or increased airway
      inflammation in chronic obstructive pulmonary disease (COPD). We compared
      adenosine and adenosine receptor (AR) expression in COPD and asymptomatic smokers
      (AS) before and after 1-year smoking cessation. Sputum cytospins and bronchial
      biopsies of (ex)smoking COPD patients and AS were studied for A(1)R, A(2A)R,
      A(2B)R, and A(3)R expression. Adenosine and inflammatory mediators were measured
      in sputum supernatants. At baseline, COPD patients had lower levels of adenosine
      and higher levels of vascular endothelial growth factor in sputum than AS.
      Smoking cessation induced significantly different effects in COPD than in AS,
      i.e. an increase in percentages of A(3)R expressing neutrophils and A(1)R
      expressing macrophages in COPD as increase in adenosine and monocyte
      chemoattractant protein-1 levels in sputum. Adenosine-related effector mechanisms
      may contribute to the persistence and progression of airway inflammation in COPD
      following 1-year smoking cessation.

PMID- 19165500
TI  - Late onset subgaleal hemorrhage infection with Streptococcus pneumoniae?
AB  - We report a case of an infected subgaleal hematoma caused by an unusual micro
      organism in a previously healthy 11-month-old girl. Our patient presented at the
      emergency department with an increasing scalp swelling for 2 weeks, and culture
      of the evacuated fluid yielded Streptococcus pneumoniae. Although she was born
      after vacuum delivery and a scalp swelling was noticed from the third day of
      life, this swelling disappeared completely at the age of 3 months. Parents were
      thoroughly questioned but we could not find out a new traumatic head event. We
      postulate that in our patient, a subgaleal hemorrhage developed after vacuum
      delivery and possibly infected 11 months later, presumably from hematogenous
      seeding of an acute otitis media. The patient recovered well after surgical
      drainage and antimicrobial therapy.

PMID- 19165498
TI  - Insights into the kinetics of Ca2+-regulated contraction and relaxation from
      myofibril studies.
AB  - Muscle contraction results from force-generating interactions between myosin
      cross-bridges on the thick filament and actin on the thin filament. The force
      generating interactions are regulated by Ca(2+) via specialised proteins of the
      thin filament. It is controversial how the contractile and regulatory systems
      dynamically interact to determine the time course of muscle contraction and
      relaxation. Whereas kinetics of Ca(2+)-induced thin-filament regulation is often
      investigated with isolated proteins, force kinetics is usually studied in muscle
      fibres. The gap between studies on isolated proteins and structured fibres is now
      bridged by recent techniques that analyse the chemical and mechanical kinetics of
      small components of a muscle fibre, subcellular myofibrils isolated from skeletal
      and cardiac muscle. Formed of serially arranged repeating units called
      sarcomeres, myofibrils have a complete fully structured ensemble of contractile
      and Ca(2+) regulatory proteins. The small diameter of myofibrils (few
      micrometres) facilitates analysis of the kinetics of sarcomere contraction and
      relaxation induced by rapid changes of [ATP] or [Ca(2+)]. Among the processes
      studied on myofibrils are: (1) the Ca(2+)-regulated switch on/off of the troponin
      complex, (2) the chemical steps in the cross-bridge adenosine triphosphatase
      cycle, (3) the mechanics of force generation and (4) the length dynamics of
      individual sarcomeres. These studies give new insights into the kinetics of thin
      filament regulation and of cross-bridge turnover, how cross-bridges transform
      chemical energy into mechanical work, and suggest that the cross-bridge ensembles
      of each half-sarcomere cooperate with each other across the half-sarcomere
      borders. Additionally, we now have a better understanding of muscle relaxation
      and its impairment in certain muscle diseases.

PMID- 19165501
TI  - Determinants of cognitive ability at 7 years: a longitudinal case-control study
      of children born small-for-gestational age at term.
AB  - The aim of this study was to identify the determinants of children's intelligence
      at 7 years, including pregnancy, postnatal, demographic factors, and small-for
      gestational age (SGA) birth at term. Information was collected at birth (n =
      871), 1 year (n = 744), 3.5 years (n = 550), and 7 years (n = 591). Approximately
      half of the children in this study were born SGA (birthweight <or=10th
      percentile). There was no significant difference found between IQ scores for SGA
      children compared to AGA children, after adjustment for potential confounders (p
      = 0.45). Paternal education, developmental delay, and birth order were associated
      with intelligence scores at 7 years in the multiple regression analysis. This
      study found no long-term effect of SGA birth at term on intelligence in middle
      childhood. Potentially modifiable postnatal and demographic factors were found to
      be strong predictors of intelligence at 7 years.

PMID- 19165503
TI  - Signal sequence analysis of protein sequences from the filarial nematode parasite
      Brugia malayi and the evolution of secreted proteins in parasites.
AB  - Taking a genomic approach to characterize potential secreted products, we
      analyzed putative protein sequences from Brugia malayi whole-genome shotgun
      sequencing project. SignalP analysis was applied to predict protein sequences and
      to identify potential signal peptides and anchors. We randomly analyzed 552
      sequences, of which 88 (15.9%) bear predicted signal sequence coding regions.
      Through comparisons of sequences with homologs from other species, we found that
      although some of the sequences with signal sequences have no homologs with
      others, there are almost the same amounts of the sequences with signals which are
      highly conserved. Considering the distribution of secretory proteins of B. malayi
      in three categories has not made big differences, and most of the homologues of
      free-living nematodes of these secretory proteins also contained either N-signal
      signal peptides or signal anchors; we speculated that secretory proteins may be
      in the same evolutional status as the non-secretory proteins.

PMID- 19165502
TI  - Laboratory study on larvicidal activity of indigenous plant extracts against
      Anopheles subpictus and Culex tritaeniorhynchus.
AB  - Anopheles subpictus and Culex tritaeniorhynchus have developed resistance to
      various synthetic insecticides, making its control increasingly difficult.
      Insecticides of botanical origin may serve as suitable alternative biocontrol
      techniques in the future. The leaf acetone, chloroform, ethyl acetate, hexane,
      and methanol extracts of Aegle marmelos (Linn.) Correa ex Roxb, Andrographis
      lineata Wallich ex Nees., Andrographis paniculata (Burm.f.) Wall. ex Nees.,
      Cocculus hirsutus (L.) Diels, Eclipta prostrata L., and Tagetes erecta L. were
      tested against fourth-instar larvae of malaria vector, A. subpictus Grassi and
      Japanese encephalitis vector, C. tritaeniorhynchus Giles (Diptera: Culicidae).
      All plant extracts showed moderate larvicidal effects after 24 h of exposure at
      1,000 ppm; however, the highest larval mortality was found in leaf ethyl acetate
      of A. marmelos, E. prostrata, hexane, methanol of A. paniculata and C. hirsutus
      against the larvae of A. subpictus (LC(50) = 167.00, 78.28, 67.24, 142.83 ppm;
      LC(90) = 588.31, 360.75, 371.91, and 830.01 ppm) and against the larvae of C.
      tritaeniorhynchus (LC(50) = 99.03, 119.89, 88.50, 105.19 ppm; LC(90) = 479.23,
      564.85, 416.39, and 507.86 ppm), respectively. These results suggest that the
      leaf hexane extract of A. paniculata and ethyl acetate extract of E. prostrata
      have the potential to be used as an ideal eco-friendly approach for the control
      of the A. subpictus and C. tritaeniorhynchus. Therefore, this study provides
      first report on the mosquito larvicidal activity of plant extracts against
      vectors from Southern India.

PMID- 19165504
TI  - Prednisone dosing per body weight or body surface area in children with nephrotic
      syndrome: is it equivalent?
AB  - The current guidelines recommend a dosage of prednisone of 60 mg/m(2) body
      surface area per day (BSA PRED) for the initial therapy of nephrotic syndrome
      (NS). Alternatively, a dosage of 2 mg/kg body weight per day (W PRED) can be
      used. We hypothesized that the BSA PRED and W PRED are not equivalent and
      analyzed the differences between BSA PRED calculated with various formulas for
      body surface area (BSA), W PRED and the dose of prednisone prescribed for our
      patients. We performed a retrospective chart review of the patients at their
      initial presentation of NS. Thirty-three children were included, of median age
      3.34 years at presentation. The W PRED was significantly lower than BSA PRED (P <
      0.05), with a median W PRED:BSA PRED ratio of 0.85 [interquartile range (IQR) 0.8
      to 0.9]. The difference between W PRED and BSA PRED decreased proportionally to
      patients' weights up to 30 kg. No differences were noted between the various BSA
      formulas using both weight and height for the calculation of BSA. The Bland
      Altman analysis showed a proportional error between W PRED and BSA PRED up to the
      average daily dose of 60 mg, with a mean bias of 0.86 (95% limits of agreement =
      0.68 to 1.05). Ten out of the 33 patients (30%) were given a lower than
      recommended BSA PRED dose by more than 5 mg/day. In conclusion, the dosage of
      prednisone at 2 mg/kg per day versus 60 mg/m(2) per day is not equivalent for
      patients with weights <30 kg and/or dose <60 mg/day.

PMID- 19165505
TI  - [Functional abdominal pain in childhood].
AB  - Functional abdominal pain is one of the most common types of recurrent pediatric
      pain. This paper gives an overview of the etiopathogenesis, diagnostic criteria,
      and cognitive-behavioral intervention strategies for functional abdominal pain.
      It addresses the issues of organic causes, psychosocial stressors, and family and
      social conditions, as well as operant processes.

PMID- 19165506
TI  - The demands of professional opera singing on cranio-cervical posture.
AB  - Difficulty with singing is a rare but important complication following cervical
      spine surgery but there is little objective information regarding the cervical
      and head postural changes taking place during singing. The aim of this study was
      to identify postural changes in the cranio-cervical region associated with the
      demands of voice production in professional opera singing. The two Roentgen
      cephalograms, one of which are taken whilst performing a specified singing task
      were taken from 18 professional opera students, 12 females (mean age 20.86 +/-
      3.07 years) and six males (18.66 +/- 1.36 years). A paired t test compared mean
      cranio-cervical postural and pharyngeal/hyoid variables between the two
      registrations (P = 0.05). The association between the cranio-cervical postural
      variables and the pharyngeal/hyoid region in each registration position was
      examined using Spearman's rank correlation coefficient. In singing, the position
      of the atlas with respect to the true vertical (P < 0.001), the axis (P < 0.001)
      and the C4 vertebra both with respect to the horizontal (P < 0.001), and the axis
      with respect to the cranium (P < 0.001), were all significantly different to
      those at rest. Of the cranio-cervical postural variables in the singing
      registration, the angles measuring positional change of the atlas and C4 relative
      to the true horizontal were shown be significantly related to an increased
      pharyngeal airway space at the C3 level (P < 0.01). An appreciation of the
      requirement for the cervical spine to undergo postural change during professional
      opera singing has relevance to the potential impact on voice quality in
      professional opera singers should they undergo cervical spine surgery.

PMID- 19165507
TI  - Arthrodesis to L5 versus S1 in long instrumentation and fusion for degenerative
      lumbar scoliosis.
AB  - There is a debate regarding the distal fusion level for degenerative lumbar
      scoliosis. Whether a healthy L5-S1 motion segment should be included or not in
      the fusion remains controversial. The purpose of this study was to determine the
      optimal indication for the fusion to the sacrum, and to compare the results of
      distal fusion to L5 versus the sacrum in the long instrumented fusion for
      degenerative lumbar scoliosis. A total of 45 patients who had undergone long
      instrumentation and fusion for degenerative lumbar scoliosis were evaluated with
      a minimum 2 year follow-up. Twenty-four patients (mean age 63.6) underwent fusion
      to L5 and 21 patients (mean age 65.6) underwent fusion to the sacrum.
      Supplemental interbody fusion was performed in 12 patients in the L5 group and
      eleven patients in the sacrum group. The number of levels fused was 6.08 segments
      (range 4-8) in the L5 group and 6.09 (range 4-9) in the sacrum group.
      Intraoperative blood loss (2,754 ml versus 2,938 ml) and operative time (220 min
      versus 229 min) were similar in both groups. The Cobb angle changed from 24.7
      degrees before surgery to 6.8 degrees after surgery in the L5 group, and from
      22.8 degrees to 7.7 degrees in the sacrum group without statistical difference.
      Correction of lumbar lordosis was statistically better in the sacrum group (P =
      0.03). Less correction of lumbar lordosis in the L5 group seemed to be associated
      with subsequent advanced L5-S1 disc degeneration. The change of coronal and
      sagittal imbalance was not different in both groups. Subsequent advanced L5-S1
      disc degeneration occurred in 58% of the patients in the L5 group. Symptomatic
      adjacent segment disease at L5-S1 developed in five patients. Interestingly, the
      development of adjacent segment disease was not related to the preoperative grade
      of disc degeneration, which proved minimal degeneration in the five patients. In
      the L5 group, there were nine patients of complications at L5-S1 segment,
      including adjacent segment disease at L5-S1 and loosening of L5 screws. Seven of
      the nine patients showed preoperative sagittal imbalance and/or lumbar
      hypolordosis, which might be risk factors of complications at L5-S1. For the
      patients with sagittal imbalance and lumbar hypolordosis, L5-S1 should be
      included in the fusion even if L5-S1 disc was minimal degeneration.

PMID- 19165508
TI  - Extraforaminal ligament attachments of the thoracic spinal nerves in humans.
AB  - An anatomical study of the extraforaminal attachments of the thoracic spinal
      nerves was performed using human spinal columns. The objectives of the study are
      to identify and describe the existence of ligamentous structures at each thoracic
      level that attach spinal nerves to structures at the extraforaminal region.
      During the last 120 years, several mechanisms have been described to protect the
      spinal nerve against traction. All the described structures were located inside
      the spinal canal proximal to the intervertebral foramen. Ligaments with a
      comparable function just outside the intervertebral foramen are mentioned
      ephemerally. No studies are available about ligamentous attachments of thoracic
      spinal nerves to the spine. Five embalmed human thoracic spines (Th2-Th11) were
      dissected. Bilaterally, the extraforaminal region was dissected to describe and
      measure anatomical structures and their relationships with the thoracic spinal
      nerves. Histology was done at the sites of attachment of the ligaments to the
      nerves and along the ligaments. The thoracic spinal nerves are attached to the
      transverse process of the vertebrae cranial and caudal to the intervertebral
      foramen. The ligaments consist mainly of collagenous fibers. In conclusion, at
      the thoracic level, direct ligamentous connections exist between extraforaminal
      thoracic spinal nerves and nearby structures. They may serve as a protective
      mechanism against traction and compression of the nerves by positioning the nerve
      in the intervertebral foramen.

PMID- 19165509
TI  - Comparison of kyphoplasty with use of a calcium phosphate cement and non
      operative therapy in patients with traumatic non-osteoporotic vertebral
      fractures.
AB  - One of the current standard treatment options for younger patients with stable
      traumatic vertebral fractures is conservative treatment using braces. Kyphoplasty
      as a minimally invasive procedure has been shown to be effective in stabilizing
      vertebral body fractures, resulting in immediate pain relief and improved
      physical function. The purpose of this prospective study was to clarify whether
      patients with acute traumatic vertebral fractures benefit more from kyphoplasty
      or from conservative treatment with a brace. A prospective study was undertaken
      in two centers. Forty patients with acute painful traumatic vertebral body
      fractures type A1-A3 (AO-classification) after adequate trauma, without
      osteoporosis, suitable for kyphoplasty or therapy by brace were included into the
      study. Follow-up was 12 months. Patients of the kyphoplasty group showed an
      immediate beneficial and significant effect postoperatively, and better outcomes
      1 and 3 months after operation compared to the conservatively treated group in
      pain feeling, mobility and vertebral body height. After 12 months the difference
      between both groups was not significant excepting the vertebral body height.
      Kyphoplasty provides early and lasting reduction of pain and improvement of daily
      activity. However, there are clinically asymptomatic cement leakages in up to 45%
      of which we do not know the consequences in long term. Every patient with
      traumatic vertebral body fracture treated by kyphoplasty has to be informed about
      that. Long-time results are outstanding and our findings require confirmation by
      randomized controlled trials.

PMID- 19165510
TI  - Interobserver reliability and intraobserver reproducibility of powers ratio for
      assessment of atlanto-occipital junction: comparison of plain radiography and
      computed tomography.
AB  - Powers ratio, as assessed on plain radiographs or computed tomography (CT)
      images, appears to have clinical and prognostic value. To date, the validation of
      this assessment tool has been limited to a small number of observers at a single
      site. No study has examined the intraobserver reproducibility and interobserver
      reliability of the Powers ratio measurement on plain radiographs or CT images
      among a large cohort of spine surgeons. This type of validation is critical to
      allow for the broader use of the Powers ratio methodology in research studies and
      clinical applications. Plain radiographs and spiral CT images of the cervical
      spine of 32 patients were assessed, and the Powers ratio was determined by five
      spine surgeons. Each surgeon performed three readings, 7 months apart. In the
      first round of measurements, the observers used only the Powers' method of
      instruction. The second and third measurement sets were obtained after an
      interactive teaching session on the methodology. The order of the images was
      altered for the second and third set of measurements. The coefficient of
      variation (Cv) was calculated to determine the intraobserver repeatability and
      interobserver reliability for each imaging technique. A Bland-Altman plot was
      then used to assess the agreement between the two imaging techniques. For
      interobserver reliability, the mean Cv of the Powers ratio was 9.09 and 4.31% for
      plain radiographs and CT, respectively. The Cv mean value for intraobserver
      reproducibility averaged 4.95% (range 1.39-9.08) when CT scans were used and
      14.17% (range 7.54-34.30) when plain radiographs were used. For intraobserver
      reproducibility, the lowest and highest Cv mean value of five raters was 1.39 and
      9.08% using CT scans and 7.54 and 34.3% using plain radiographs. The Bland-Altman
      plot, demonstrated that the two methods were in close agreement on the -0.8 and
      0.89% interval for limits of agreement (bias +/- 1.96sigma). The intraobserver
      reproducibility and interobserver reliability of Powers ratio measurement was
      acceptable (<5%) with CT scans but not with plain radiographs. However, despite
      the statistically inferior reliability and repeatability, the Bland-Altman plot
      analysis showed that given the -0.8 and 0.89% limits of agreement, the two
      methods may be used interchangeably in clinical practice.

PMID- 19165511
TI  - Long-term follow-up of functioning after spinal surgery in patients with Rett
      syndrome.
AB  - In a prospective study, 23 consecutive girls with Rett syndrome and neuromuscular
      scoliosis were evaluated for functioning at a long-term follow-up. The patients
      had mostly improved, which was confirmed by their parents. Rett syndrome is
      associated with neuromuscular scoliosis and has a typically long C-shaped
      thoracolumbar kyphoscoliosis. Prospective long-term follow-up studies related to
      these patients' total situation are sparse. Most studies focus on the Cobb angle
      of the scoliosis, whereas parents are mainly concerned about the girls' continued
      functioning. Twenty-three patients with Rett syndrome and neuromuscular scoliosis
      were evaluated preoperatively from 1993 to 2002. At follow-up, 19 patients
      remained in the study. Three patients died (not due to surgery), and one patient
      could not participate because it was too far to travel. Mean follow-up time was
      74 months (range 49-99 months). The assessments comprised the sitting balance,
      seating supports in wheelchair, weight distribution, time used for rest, care
      given, and angle of scoliosis. Follow-up questionnaires and two-open-ended
      questions about the positive and negative effects of surgery were sent to
      parents. Sitting balance, number of seating supports in wheelchair, weight
      distribution, time used for rest, and the Cobb angle had all improved after
      surgery. The parents assessed improvement in seating position, daily activities,
      time used for rest, and cosmetic appearance. We can conclude that the stabilized
      spine resulted in sufficient strength to keep the body upright with the
      possibility of looking around at the surroundings more easily. The girls got
      better seating position with less need for seating adaptations in the wheelchair
      and with reduced time needed for resting during the day. Finally we can conclude
      that the indication for surgery is to get a better posture which lead to less
      risk of pressure sores, and that un upright position lead to better possibility
      to easily breath with fewer episodes of pneumonia and a better general health as
      result. The evidence of positive surgical effects for girls with Rett syndrome is
      of great importance in indication for surgery in the decision-making process.

PMID- 19165512
TI  - Calcification in the ovine intervertebral disc: a model of hydroxyapatite
      deposition disease.
AB  - The study design included a multidisciplinary examination of the mineral phase of
      ovine intervertebral disc calcifications. The objective of the study was to
      investigate the mineral phase and its mechanisms of formation/association with
      degeneration in a naturally occurring animal model of disc calcification. The
      aetiology of dystrophic disc calcification in adult humans is unknown, but occurs
      as a well-described clinical disorder with hydroxyapatite as the single mineral
      phase. Comparable but age-related pathology in the sheep could serve as a model
      for the human disorder. Lumbar intervertebral discs (n = 134) of adult sheep of
      age 6 years (n = 4), 8 years (n = 12) and 11 years (n = 2) were evaluated using
      radiography, morphology, scanning and transmission electron microscopy, energy
      dispersive X-ray spectroscopy, X-ray powder diffraction, histology,
      immunohistology and proteoglycan analysis. Half of the 6-year, 84% of the 8-year
      and 86% of the 11-year-old discs had calcific deposits. These were not well
      delineated by plain radiography. They were either: (a) punctate deposits in the
      outer annulus, (b) diffuse deposits in the transitional zone or inner annulus
      fibrosus with occasional deposits in the nucleus, or (c) large deposits in the
      transitional zone extending variably into the nucleus. Their maximal incidence
      was in the lower lumbar discs (L4/5-L6/7) with no calcification seen in the
      lumbosacral or lower thoracic discs. All deposits were hydroxyapatite with large
      crystallite sizes (800-1,300 A) compared to cortical bone (300-600 A). No type X
      collagen, osteopontin or osteonectin were detected in calcific deposits, although
      positive staining for bone sialoprotein was evident. Calcified discs had less
      proteoglycan of smaller hydrodynamic size than non-calcified discs. Disc
      calcification in ageing sheep is due to hydroxyapatite deposition. The variable,
      but large, crystal size and lack of protein markers indicate that this does not
      occur by an endochondral ossification-like process. The decrease in disc
      proteoglycan content and size suggests that calcification may precede or
      predispose to disc degeneration in ageing sheep.

PMID- 19165513
TI  - Auranofin disrupts selenium metabolism in Clostridium difficile by forming a
      stable Au-Se adduct.
AB  - Clostridium difficile is a nosocomial pathogen whose incidence and importance are
      on the rise. Previous work in our laboratory characterized the central role of
      selenoenzyme-dependent Stickland reactions in C. difficile metabolism. In this
      work we have identified, using mass spectrometry, a stable complex formed upon
      reaction of auranofin (a gold-containing drug) with selenide in vitro. X-ray
      absorption spectroscopy supports the structure that we proposed on the basis of
      mass-spectrometric data. Auranofin potently inhibits the growth of C. difficile
      but does not similarly affect other clostridia that do not utilize selenoproteins
      to obtain energy. Moreover, auranofin inhibits the incorporation of radioisotope
      selenium ((75)Se) in selenoproteins in both Escherichia coli, the prokaryotic
      model for selenoprotein synthesis, and C. difficile without impacting total
      protein synthesis. Auranofin blocks the uptake of selenium and results in the
      accumulation of the auranofin-selenide adduct in the culture medium. Addition of
      selenium in the form of selenite or L-selenocysteine to the growth medium
      significantly reduces the inhibitory action of auranofin on the growth of C.
      difficile. On the basis of these results, we propose that formation of this
      complex and the subsequent deficiency in available selenium for selenoprotein
      synthesis is the mechanism by which auranofin inhibits C. difficile growth. This
      study demonstrates that targeting selenium metabolism provides a new avenue for
      antimicrobial development against C. difficile and other selenium-dependent
      pathogens.

PMID- 19165514
TI  - The role of fractionated radiotherapy and radiosurgery in the management of
      patients with craniopharyngioma.
AB  - The optimal management of craniopharyngiomas remains controversial. The first
      line treatment usually consists of surgical resection. Complete tumor removal
      provides a high rate of long-term control; however, aggressive surgery is
      associated with significant incidence of complications. Radiotherapy (RT) is
      currently used in patients after limited surgery and achieves excellent long-term
      tumor control. Stereotactic radiotherapy, both in the form of radiosurgery (RS)
      or fractionated stereotactic radiotherapy (FSRT), has been developed as a more
      accurate technique of irradiation with more precise tumor localization and
      consequently a reduction in the volume of normal brain irradiated to high
      radiation doses. We provide a review of published data on outcome of conventional
      fractionated RT and modern radiation techniques. FSRT is a suitable treatment
      technique for all sizes of craniopharyngiomas, and efficacy is comparable to
      conventional RT. Single-fraction stereotactic radiosurgery is usually delivered
      to small tumors away from critical structures. Longer follow-up is necessary to
      confirm the excellent tumor control and the potential reduction of long-term
      radiation toxicity.

PMID- 19165515
TI  - Dysembryoplastic neuroepithelial tumor: a clinicopathological study of 32 cases.
AB  - Dysembryoplastic neuroepithelial tumor (DNT) is a relatively newly described
      entity and is an important cause of intractable epilepsy. We report 32 cases of
      DNT who were operated and treated in our hospital over a period of 12 years.
      Immunostaining for various proliferative markers and tumor suppressor gene
      proteins was done to assess the proliferative potential of these tumors. The most
      common presentation was partial complex seizures followed by generalized tonic
      clonic seizures, focal motor seizures, and myoclonus. The most common location
      was temporal lobe followed by frontal and in one patient lesion was multifocal.
      All patients were seizure free at the last postoperative follow-up which varies
      from 12 to 96 months with mean of 33.7 months. Microscopic examination showed
      classical histology comprising of intracortical multinodular microcystic lesions
      with floating neurons. Proliferative indices were very low (<1%) and tumor
      suppressor gene protein expression was not seen in the present study. Cortical
      dysplasia of the surrounding brain was observed in 37.3% of cases.

PMID- 19165516
TI  - A thiol-activated lipase from Trichosporon asahii MSR 54: detergent compatibility
      and presoak formulation for oil removal from soiled cloth at ambient temperature.
AB  - An alkaline lipase from Trichosporon asahii MSR 54 was used to develop presoak
      formulation for removing oil stains at ambient temperature. The lipase was
      produced in a reactor followed by concentration by ultrafiltration and then it
      was dried with starch. The biochemical characteristics of enzyme showed that it
      was an alkaline lipase having pH activity in the range of pH 8.0-10.0 and
      temperature in the range of 25-50 degrees C. The present lipase was active >80%
      at 25 degrees C. The lipase was cystein activated with fourfold enhancement in
      presence of 5 mM cystein and likewise the activity was also stimulated in
      presence of papain hydrolysate which served as source of cystein. The presoak
      formulation consisted of two components A and B, component A was enzyme additive
      and B was a mixture of carbonate/bicarbonate source of alkali and papain
      hydrolysate as source of cystein. The results indicated that the presoaking in
      enzyme formulation followed by detergent washing was a better strategy for stain
      removal than direct washing with detergent in presence of lipase. Further, it was
      observed that 0.25% presoak component B in presence of 100 U enzyme component A
      (0.1 g) was the best formulation in removing maximum stain from mustard
      oil/triolein soiled clothes as indicated by increase in reflectance which was
      found equal to that of control cloth. The lipase action in presoaked formulation
      was clearly indicated by quantitated fatty acid release and also the TLC results
      of wash water, where oil hydrolytic products were visible only in presence of
      enzyme in the treatment. The wash performance carried at 25 degrees C indicated
      that washing at 25 degrees C was at par with that at 40 degrees C as indicated by
      similar reflectance of the washed cloth piece though qualitative fatty acid
      release was higher at 40 degrees C.

PMID- 19165517
TI  - Tilted disc syndrome: an OCT and mfERG study.
AB  - PURPOSE: To evaluate retinal thickness and function in eyes with tilted disc
      syndrome with optical coherence tomography (OCT) and multifocal electroretinogram
      (mfERG). METHODS: Twenty-one eyes of 12 patients (4 males and 8 females) with
      tilted disc were studied with OCT3 and mfERG and compared with 40 eyes of 20 age
      and sex-matched control subjects. The thickness of the fovea and the thickness of
      retinal nerve fibre layer (RNFL) along a 3.4-mm-diameter circle centred on the
      optic nerve head were evaluated using OCT3. The macular cone function was tested
      by mfERG. RESULTS: The OCT-derived RNFL thickness was significantly decreased in
      the superior area of eyes with tilted disc with a mean value equal to 106.47
      microm (SD 24.1). The mean response amplitude density of the fovea (11.75
      nV/deg(2)) and parafovea (8.22 nV/deg(2)) was significantly lower in eyes with
      tilted disc than in normal eyes. CONCLUSION: OCT and mfERG can be objective tools
      for assessing anatomical and functional damage of the macula. Our results suggest
      that in tilted disc syndrome even without visual impairment the optic nerve and
      the macula show dysfunction not visible by other means.

PMID- 19165521
TI  - Purified chickpea or lentil proteins impair VLDL metabolism and lipoprotein
      lipase activity in epididymal fat, but not in muscle, compared to casein, in
      growing rats.
AB  - BACKGROUND: It is well known that the legume proteins have a lowering effect on
      plasma cholesterol and triacylglycerols (TG) concentrations compared to animal
      proteins. The protein itself, as well as non-protein constituents, naturally
      present in legumes may be implicated. AIM OF THE STUDY: The effects of various
      dietary purified legumes proteins compared to casein, were determined on plasma
      TG level, VLDL concentration and composition. Moreover, lipoprotein lipase (LPL)
      activity in epididymal fat, gastrocnemius and heart was investigated to evaluate
      in these tissues their capacity to release free fatty acids from their TG
      substrate and the liver capacity to stock the TG. METHODS: Weaning male Wistar
      rats were fed ad libitum one of the following diets: 200 g/kg diet of purified
      proteins of lentil (L), or chickpea (CP) or casein (CAS). At day 28, VLDL were
      isolated from plasma sample by a single ultracentrifugation flotation. Hepatic
      lipase and LPL activity in epididymal fat, gastrocnemius and heart were measured
      by using glycerol tri [9-10(n)-(3)H] oleate emulsion as substrate. RESULTS:
      Compared with CAS diet, the CP and L protein diets exhibited similar
      cholesterolemia, but lower triglyceridemia (1.9-fold and 2.5-fold) and VLDL
      particle number, as measured by their reduced contents of TG and apolipoproteins.
      CP and L protein diets reduced liver TG and cholesterol by 31 and 45%,
      respectively compared to CAS diet. Furthermore, LPL activity in adipose tissue of
      rats fed CP or L was 1.6-fold lower than that of rats fed CAS. There was no
      significant difference in heart and gastrocnemius LPL activities with the three
      proteins. In contrast, hepatic lipase activity was higher in rats fed CP and L
      diets. CONCLUSION: The low food efficiency ratio of purified CP and L proteins
      related to CAS is associated with decreased plasma VLDL and adipose tissue LPL
      activity. The low liver TG concomitant with reduced TG and apolipoproteins
      contents of VLDL confirm that hypotriglyceridemia is essentially due to impaired
      synthesis, exportation and transport of TG by VLDL which prevent lipid storage in
      adipose tissue.

PMID- 19165522
TI  - Biotin deficiency in mice is associated with decreased serum availability of
      insulin-like growth factor-I.
AB  - BACKGROUND: Biotin deficiency leads to decreased weight and nose-rump length in
      mice. AIM OF THE STUDY: The mechanisms underlying this impairment in body growth
      are yet unclear. Biotin restriction, however, could affect the availability of
      growth hormone (GH) and/or insulin like growth factor-I (IGF-I) since both
      hormones control body growth. We then conducted a correlative study aimed at
      establishing whether biotin dietary restriction is associated with decreased
      GH/IGF-I serum concentrations. METHODS: Levels of GH and IGF-I were measured
      through ELISA in serum samples of male BALB/cAnN mice fed with: 1] standard chow
      diet (control diet); 2] 30% egg-white biotin-deficient diet; or 3] 30% egg-white
      diet supplemented with 16.4 micromol biotin per kilogram (biotin sufficient
      diet). Relative food consumption, as adjusted per gram of body weight, was also
      determined. GH and IGF-I measurements were taken individually for 20 weeks
      beginning at the postnatal week 3, when the animals started consuming the
      corresponding diets. In addition, femur's weight and longitudinal growth and the
      organization of its growth plate were all analyzed as indicators of GH/IGF-I
      function. RESULTS: No differences in relative food consumption were observed
      among the three groups of mice along the experimental period that was evaluated.
      IGF-I serum levels, but not GH ones, were decreased in biotin deficient mice.
      These animals also showed decreased femur's longitudinal growth, speed of
      lengthening and weight gain, as well as shorter and disorganized growth plates.
      CONCLUSIONS: This study shows that biotin dietary restriction is indeed
      associated with decreased availability of IGF-I and diminished long bone growth
      and elongation. These conditions could explain the impairment of longitudinal
      body growth previously reported in biotin deficient mice. Although cause-effect
      studies are still needed, we believe our results support the notion that biotin
      might modulate the availability of IGF-I.

PMID- 19165523
TI  - Binocular depth inversion as a paradigm of reduced visual information processing
      in prodromal state, antipsychotic-naive and treated schizophrenia.
AB  - The binocular depth inversion illusion test (BDII) represents a sensitive measure
      of impaired visual information processing that manifests in various experimental
      and naturally occurring psychotic states. This study explores impairment of
      visual processing in different major psychiatric diseases investigating 313
      subjects, suffering of either an initial prodromal state of psychosis (IPS) or a
      first-episode, antipsychotic-naive paranoid schizophrenia (SZ-N) as well as short
      term antipsychotically treated schizophrenia (SZ-T), major depression (MDD),
      bipolar disorder (BD), dementia (D), and healthy controls (HC). Patients
      suffering from either IPS, SZ-N or a SZ-T showed significantly higher scores of
      BDII compared to HC, indicating that visual processing is already disturbed at an
      early state of the disease. For MDD, BD and D no statistically significant
      difference was found compared to HC. As the identification of individuals at high
      risk for developing schizophrenia relies on rating scales assessing subtle, pre
      psychotic psychopathology, it would be of interest to have more diagnostic
      criteria available, testing, e.g. cognitive and perceptual impairment. We
      therefore analysed the receiver operating characteristic (ROC) curve, testing
      prodromal cases versus a clinically relevant sample of non-psychotic patients and
      controls, which included HC as well as the groups of patients suffering from MDD,
      BD or D revealing a AUC of 0.70. Thus, the BDII may be useful as an additional
      neuropsychological test for assessment of patients at high risk for developing
      schizophrenia.

PMID- 19165524
TI  - Exploratory eye movement dysfunction as a discriminator for schizophrenia : a
      large sample study using a newly developed digital computerized system.
AB  - In our previous studies, we identified that exploratory eye movement (EEM)
      dysfunction appears to be specific to schizophrenia. The availability of a
      biological marker specific to schizophrenia would be useful for clinical
      diagnosis of schizophrenia. Consequently, we performed the discriminant analysis
      between schizophrenics and non-schizophrenics on a large sample using the EEM
      test data and examined an application of the EEM for clinical diagnosis of
      schizophrenia. EEM performances were recorded in 251 schizophrenics and 389 non
      schizophrenics (111 patients with mood disorders, 28 patients with neurotic
      disorders and 250 normal controls). The patients were recruited from eight
      university hospitals and three affiliated hospitals. For this study with a large
      sample, we developed a new digital computerized version of the EEM test, which
      automatically handled large amounts of data. We measured four parameters: number
      of eye fixations (NEF), total eye scanning length (TESL), mean eye scanning
      length (MESL) and responsive search score (RSS). These parameters of
      schizophrenics differed significantly from those of the other three groups. The
      stepwise regression analysis selected the TESL and the RSS as the valid
      parameters for discriminating between schizophrenics and non-schizophrenics. In
      the discriminant analysis using the RSS and TESL as prediction parameters, 184 of
      the 251 clinically diagnosed schizophrenics were discriminated as having
      schizophrenia (sensitivity 73.3%); and 308 of the 389 clinically diagnosed non
      schizophrenic subjects were discriminated as non-schizophrenics (specificity
      79.2%). Based on our findings we believe that the EEM measures may be useful for
      the clinical diagnosis of schizophrenia.

PMID- 19165525
TI  - The effect of venlafaxine compared with other antidepressants and placebo in the
      treatment of major depression: a meta-analysis.
AB  - OBJECTIVE: Meta-analysis of all available trials of Venlafaxine in the treatment
      of major depressive disorders, including treatment resistant depression and long
      term relapse prevention. METHODS: We conducted a meta-analysis comparing
      venlafaxine and tricyclics, or selective serotonin reuptake inhibitors (SSRIs),
      in major depression. We also included trials comparing venlafaxine and
      alternative antidepressants in subjects with treatment resistant depression, or
      compared with placebo in long-term relapse prevention. Trials were identified
      through searches of Medline, Embase, Cochrane Library and through accessing
      unpublished trials held by the manufacturer. Results based on intention to treat
      analyses where available, were pooled using theoretically exact conditional
      maximum likelihood methods for fixed effects (primary analyses), and numerical
      simulation using a Gibbs sampler for full random effects. RESULTS: Compared to
      all SSRIs for the treatment of major depression (fluoxetine, paroxetine,
      sertraline, citalopram, escitalopram and fluvoxamine), venlafaxine was associated
      with a greater response [odds ratio 1.15 (95% CI 1.02-1.29)] and remission [odds
      ratio 1.19 (95% CI 1.06-1.34)]. Overall drop out rates appeared similar for SSRIs
      and venlafaxine. Compared to tricyclics, response to venlafaxine was estimated to
      be greater by exact method, odds ratio 1.21 (95% CI 1.03-1.43), but not
      statistically significantly different, using a full random effects method odds
      ratio 1.22 (95% CI 0.96-1.54). We observed no difference in remission rates (odds
      ratio 1.06 (95% CI 0.74-1.63)). Tricyclics were less well tolerated with higher
      overall drop out rates. Compared to alternative antidepressants in treatment
      resistant depression (trials included comparison with sertraline, bupropion,
      fluoxetine, citalopram, and one with a range of agents-mostly SSRIs), the odds
      ratio for response was 1.35 (95% CI 1.19-1.54). The odds ratio for remission was
      1.35 (95% CI 1.20-1.52). Compared to placebo the odds ratio for relapse
      prevention with venlafaxine was 0.37 (95% CI 0.27-0.51). CONCLUSION: This meta
      analysis provides evidence of the clinical efficacy of venlafaxine in achieving
      therapeutic response and remission in patients with major depression. Venlafaxine
      appears more effective than SSRIs, and at least as effective as tricyclic
      antidepressants, in the treatment of major depressive episode. Venlafaxine
      appeared more effective than comparators in treatment resistant depression. In
      addition, venlafaxine effective in reducing relapse when given long term after
      major depressive episode.

PMID- 19165526
TI  - Creating a map of psychiatric patients based on psychopathological symptom
      profiles.
AB  - BACKGROUND: In the current debate about the categorical or dimensional
      classification of mental disorders many fruitful methods to illustrate one or the
      other aspect are employed, and suggestions are made to combine the two
      perspectives. METHODS: We present such an approach to combine both perspectives
      at the same time. Based on psychopathological AMDP-symptom profiles, a map of
      psychiatric patients was calculated by robust nonmetric multidimensional scaling
      (NMDS). RESULTS: The sample from the Ludwig-Maximilians University in Munich
      included the records of patients, who were admitted and discharged in 2002 and
      2003 with a diagnosis of either paranoid schizophrenia, (F20.00, N = 24), bipolar
      affective disorder, current episode manic without psychotic symptoms (F31.1, N =
      32) or severe depressive episode without psychotic symptoms (F32.2, N = 78). In
      the resulting map of patients we found a clear categorical distinction according
      to the diagnostic groups, but also high regression values of AMDP-syndromes
      (manic syndrome: r = 0.83, depressive syndrome: r = 0.68, and paranoid
      hallucinatory syndrome, r = 0.62). DISCUSSION: The map of psychiatric patients
      presents an approach to consider the categorical and dimensional aspects at the
      same time. We were able to identify meaningful delineations between diagnostic
      clusters as well as continuous transitions. This method allows the whole
      psychopathological profile of each individual patient to be considered and also
      to identify misdiagnosed cases at a glance.

PMID- 19165527
TI  - Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis
      and immune system imbalance in schizophrenia.
AB  - Schizophrenia is a complex disease, likely to be caused by a combination of
      serial alterations in a number of genes and environmental factors. The
      dorsolateral prefrontal cortex (Brodmann's Area 46) is involved in schizophrenia
      and executes high-level functions such as working memory, differentiation of
      conflicting thoughts, determination of right and wrong concepts and attitudes,
      correct social behavior and personality expression. Global proteomic analysis of
      post-mortem dorsolateral prefrontal cortex samples from schizophrenia patients
      and non-schizophrenic individuals was performed using stable isotope labeling and
      shotgun proteomics. The analysis resulted in the identification of 1,261
      proteins, 84 of which showed statistically significant differential expression,
      reinforcing previous data supporting the involvement of the immune system,
      calcium homeostasis, cytoskeleton assembly, and energy metabolism in
      schizophrenia. In addition a number of new potential markers were found that may
      contribute to the understanding of the pathogenesis of this complex disease.

PMID- 19165528
TI  - Effects of abstinence on brain morphology in alcoholism: a MRI study.
AB  - Chronic alcohol abuse leads to morphological changes of the brain. We
      investigated if these volumetric changes are reversible after a period of
      abstinence. For this reason 41 male and 15 female alcohol patients underwent MRI
      scanning after in-patient detoxification (baseline) entering alcoholism treatment
      programs, and between 6 and 9 months later (follow-up), in a phase of
      convalescence. Additionally, 29 male and 16 female control subjects were
      examined. The MRI-scans were delineated and the resulting regions of interest,
      volumes of lateral ventricles and prefrontal lobes were expressed relatively to
      total brain volume. Compared to control subjects alcohol patients showed
      bilaterally decreased prefrontal lobes (11% reduction) and increased lateral
      ventricles (up to 42% enlargement). The extent of the ventricular increase was
      depending on patient's additional psychiatric diagnosis, showing smaller lateral
      ventricles in patients with additional personality disorder. While at follow-up
      the size of prefrontal lobes remained unchanged, volumes of the lateral
      ventricles decreased (5-6% reduction) in alcohol patients with abstinence and
      improved drinking behavior, especially in patients that underwent only one
      detoxification. The extent of the ventricular enlargement correlated with the
      elevation of alcohol related laboratory measures (mean corpuscular volume, gamma
      glutamyl transpeptidase). In conclusion this study confirms the hypothesis that
      alcoholism causes brain damages that are partially reversible. It should be
      analyzed in further studies with larger sample sizes, if complete brain
      regeneration is possible maintaining abstinence over a longer period.

PMID- 19165529
TI  - A randomised, placebo-controlled, 24-week, study of low-dose extended-release
      methylphenidate in adults with attention-deficit/hyperactivity disorder.
AB  - INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) affects many adults
      who had ADHD in childhood. Although stimulants and methylphenidate in particular
      are a common off-label treatment for adult patients with ADHD in European
      countries, little is known about their long-term efficacy and safety. METHODS: A
      randomized, 24-week double-blind, placebo-controlled, parallel-design study of
      extended-release methylphenidate (MPH ER) in 359 adult individuals with ADHD
      according to DSM-IV. Standardized instruments were used for diagnosis. Treatment
      was started with MPH ER doses of 10 mg/day and titrated up to 60 mg/day,
      depending on individual efficacy and tolerability. Mean daily MPH SR dose was
      0.55 mg/kg. RESULTS: Treatment with MPH ER resulted in clinical and statistically
      significant reductions of ADHD symptoms rated with the Wender-Reimherr adult
      attention deficit disorder scale (WRAADDS) and symptoms of inattention and
      hyperactivity/impulsivity according to DSM-IV, respectively. Improvements were
      maintained significant versus placebo up to week 24 of treatment. At endpoint,
      61% of the subjects receiving MPH ER were rated as responders according to the a
      priori definition of response of more than 30% reduction of the WRAADDS score,
      compared to 42% in the placebo group. The second defined response criterion of
      much or very much improved on the clinical global impression scale (CGI) was
      fulfilled by 55% of subjects receiving MPH ER and 37% of subjects receiving
      placebo. MPH ER treatment was associated with a statistically significant
      increase of pulse at week 4 (72 bpm at baseline, 77 bpm at week 4). There were no
      significant differences of heart rate or blood pressure between treatment and
      placebo groups at any time point. DISCUSSION: MPH ER treatment in low to moderate
      doses was effective and safe in the treatment of ADHD in adults. Efficacy
      measures were clinical and statistically significant and robustly sustained
      during the 24-week observation period. In this study, no clinical significant
      effects on blood pressure but a transient increase of the heart rate were found.
      The interpretation of the results is limited by the low dose-range used in this
      study, the high drop-out rate and placebo-response which might have affected the
      therapeutic effect size.

PMID- 19165530
TI  - Primary angiitis of the CNS mimicking a spinal cord tumour.

PMID- 19165531
TI  - Weight loss in neurodegenerative disorders.
AB  - Unintended weight loss frequently complicates the course of many
      neurodegenerative disorders and can contribute substantially to both morbidity
      and mortality. This will be illustrated here by reviewing the characteristics of
      unintended weight loss in the three major neurodegenerative disorders:
      Alzheimer's disease, Parkinson's disease and Huntington's disease. A common
      denominator of weight loss in these neurodegenerative disorders is its typically
      complex pathophysiology. Timely recognition of the underlying pathophysiological
      process is of crucial importance, since a tailored treatment of weight loss can
      considerably improve the quality of life. This treatment is, primarily, comprised
      of a number of methods of increasing energy intake. Moreover, there are
      indications for defects in the systemic energy homeostasis and gastrointestinal
      function, which may also serve as therapeutic targets. However, the clinical
      merits of such interventions have yet to be demonstrated.

PMID- 19165532
TI  - Pilot evaluation of the Frankfurt Social Skills Training for children and
      adolescents with autism spectrum disorder.
AB  - The objective of this pilot study was to evaluate the effectiveness of a group
      based intervention aiming at improving social and communication skills in
      individuals with autism spectrum disorder. Over a period of 11 months, N = 17
      children and adolescents received treatment according to the manualised Frankfurt
      Social Skills Training (KONTAKT). Parent, teacher, expert and blind expert
      ratings were assessed to judge outcome regarding peer interaction, autistic
      behaviours, adaptive functioning and family burden. The participants exhibited
      improvements pre to follow-up treatment, particularly in the area of autistic
      symptomatology. Effect sizes (partial eta squared) ranged from 0.02 to 0.69.
      Among other things, regression models showed a positive influence of IQ and
      language skills on gains in social skills. Findings indicate that KONTAKT might
      be useful for enhancing social skills and reducing autism-related psychopathology
      over time in different contexts. Nevertheless, controlled trials are needed to
      reassure its effectiveness.

PMID- 19165533
TI  - Clinical diagnoses, characteristics of risk behaviour, differences between
      suicidal and non-suicidal subgroups of Hungarian adolescent outpatients
      practising self-injury.
AB  - OBJECTIVE: Self-injury (SI), self-injurious behaviour (SIB), including suicidal
      or non-suicidal self-injury (SSI, NSSI) represent an increasing problem among
      teenagers amounting to a 6-17% prevalence rate in adolescence, yet little data
      exists on detailed characteristics and associated factors of SI reaching clinical
      severity. There is also a scarcity of data distinguishing between suicidal and
      non-suicidal subsamples of self-injuring patients, i.e. showing which predictors
      contribute to develop self-injurious behaviour with a previous suicidal history
      (SSI). METHOD: Clinical diagnoses and characteristics of risk behaviour were
      examined in a crosssectional design in suicidal and non-suicidal subgroups of
      Hungarian adolescent outpatients practising self-injurious behaviour. From the
      total pool of 708 new patients consecutively referred with various psychiatric
      problems in five regional child psychiatric centres in Western-Hungary over an 18
      month period, 105 adolescent outpatients suffering from self-injurious behaviour
      participated in the study (28 males and 77 females aged from 14 to 18 years, mean
      age 15.97, SD 1.05). The Ottawa/Queen's self-injury questionnaire (OSI) was used
      to measure the characteristics of risk behaviour, while the comorbid clinical
      diagnoses were confirmed by the M.I.N.I. Plus International Neuropsychiatric
      Interview. Descriptive statistics presented the frequencies of the
      characteristics of SI, bilateral comparisons were used to reveal relevant items
      to differentiate between sex, duration of practice and SSI versus NSSI and
      logistic regression was performed to identify significant predictors of suicidal
      subtype of self-injuring practice. RESULTS: A total of 60% of the clinical SI
      population experienced a present or past episode of major depression. The
      motivation of patients to resist impulses and to discontinue malpractice was low.
      Cutting and scratching was the most common self-injuring methods. Two-thirds of
      the sample practised the impulsive type of SI, while 30% practised premeditated
      SI having an incubation time from 30 min to days and weeks before carrying out
      SI. Although duration of SI did not distinguish the sample in important aspects,
      girls and boys differed in several aspects of SI practice. SSI adolescents
      differed from their NSSI peers in a number of important characteristics including
      the frequency of actions, injured areas, methods, specific stresses and
      motivations. SSI adolescents were more likely to favour cutting of the lower leg
      and drug overdose as modes of SI. SSI adolescents were more likely to report
      addictive features than their peers with no suicidal motivation. From the aspect
      of self-injurious practice, logistic regression analysis found only two
      significant predictors for the combined pathology.

PMID- 19165534
TI  - The German version of the Anorectic Behavior Observation Scale (ABOS).
AB  - OBJECTIVE: To assess the performance of the German version of the Anorectic
      Behavior Observation Scale (ABOS) as a parent-report screening instrument for
      eating disorders (ED) in their children. METHODS: Parents of 101 ED female
      patients (80 with Anorexia Nervosa; 21 with Bulimia Nervosa) and of 121 age- and
      socioeconomic status (SES)-matched female controls completed the ABOS. RESULTS:
      Confirmatory factor analysis supported the original three-factor structure model
      of the ABOS. Cronbach's alpha coefficients indicated good internal consistency
      for the three factors and the total score in the total sample. The best cut-off
      point (100% sensitivity and specificity) in the German version was >or=23.
      CONCLUSION: The ABOS may be a useful additional instrument for assessing ED.

PMID- 19165535
TI  - Five-year predictive validity of DSM-IV conduct disorder research diagnosis in
      4(1/2)-5-year-old children.
AB  - OBJECTIVE: This longitudinal study of a non-referred, population-based sample
      tested the 5-year predictive validity of the DSM-IV conduct disorder (CD)
      research diagnosis in children 4(1/2)-5 years of age. METHOD: In the E-Risk
      Study, a representative birth cohort of 2,232 children, mothers were interviewed
      and teachers completed mailed questionnaires to assess children's past 6-month CD
      symptoms. A follow-up assessment was conducted when children were 10 years old.
      RESULTS: CD-diagnosed 5-year-olds were significantly more likely than controls to
      have behavioural and educational difficulties at age 10. Increased risk for age
      10 educational difficulties persisted after controlling for age-5 IQ and ADHD
      diagnosis. Although the majority of CD-diagnosed 5-year-olds had no CD symptoms
      at age 10, findings suggest that these "remitted" children continued to
      experience behavioural and educational problems 5 years later despite their
      apparent remission from CD. CONCLUSIONS: DSM-IV CD symptoms validly identify
      preschool-aged children who continue to have behavioural and educational problems
      in middle-childhood.

PMID- 19165536
TI  - Assessing quality of life: mother-child agreement in depressed and non-depressed
      Hungarian.
AB  - PURPOSE: An important question in child psychiatry is the agreement between
      parents and children. We studied mother-child concordance about the quality of
      life of children (QoL). We hypothesized that mothers of depressed children rate
      lower QoL than children for themselves while mothers of non-depressed children
      rate better QoL; that inter-informant agreement is higher in the non-depressed
      sample; and finally that agreement increases with age of the child. METHODS: QoL
      of depressed children (N = 248, mean age 11.45 years, SD 2.02) were compared to
      that of non-depressed children (N = 1695, mean age 10.34 years, SD 2.19). QoL was
      examined by a 7 item questionnaire (ILK). RESULTS: Mothers of depressed children
      rated lower QoL than their children while mothers of nondepressed children rated
      higher QoL than their children. Agreement was low in both samples but higher in
      the controls. Inter-informant agreement was only influenced by depression.
      CONCLUSIONS: Our results show that mothers relate more serious negative effects
      to childhood depression than their children and rate less problems for their non
      depressed children compared to self-reports. Mother-child agreement is negatively
      influenced by depression which further stresses the importance of obtaining
      reports from the child and at least one parent in order to understand the
      subjective experiences caused by the illness.

PMID- 19165537
TI  - Symptom diagnostics based on clinical records: a tool for scientific research in
      child psychiatry?
AB  - INTRODUCTION: Child psychiatric diagnoses are generally based on a clinical
      examination and not on standardized questionnaires. The present study assessed
      whether symptom diagnostics based on clinical records facilitates the use of non
      standardized clinical material for research. METHOD: Six hundred and eighty-five
      children, referred to a third level child psychiatric centre in the Netherlands,
      were, after extensive multidisciplinary examination, classified according to the
      multi-axial classification scheme for psychiatric disorders in childhood and
      adolescence (MAC-ICD-9). By two raters 44 behavioural symptoms were scored based
      on the clinical records of these children. Interrater agreement on symptoms in 50
      records was performed. Principal components analysis on symptom scores of all
      children was performed; factor scores were related with MAC-ICD-9
      classifications. RESULTS: Interrater reliability for behavioural symptoms was
      excellent (kappa = 0.88). Many children with psychiatric problems suffer from a
      large number of behavioural symptoms. Factor scores of the symptoms revealed
      recognizable and well interpretable entities and indicated overlap in
      symptomatology and comorbidity. CONCLUSION: A symptom-based diagnostic approach
      based on extensive clinical patient files may provide a special dimension to
      improve the reliability of psychiatric classification.

PMID- 19165538
TI  - Comparing different modes of delivery: a pilot evaluation of a family-focused,
      cognitive-behavioral intervention for anxiety-disordered children.
AB  - Cognitive behavior therapy delivered by trained clinicians has been shown to be
      an effective treatment for childhood anxiety. However, the prevalence of anxiety
      disorders in children and adolescents, combined with the practical and
      psychological obstacles that often prevent families from accessing professional
      help, mean that alternative ways of reaching prospective clients must be
      explored. This pilot study aims to compare the relative efficacy of two different
      modes of delivering a family-focused, cognitive-behavioral intervention for
      children with an anxiety disorder. The two modalities compared were: a parent
      delivered program (bibliotherapy) and a clinician-delivered program (individual
      therapy). Twenty-seven children aged between 7 and 14, together with their
      parents, were randomly assigned to one of the two conditions listed above.
      Results at post-treatment showed a significant improvement for children in both
      treatment conditions in terms of diagnostic status, number of diagnoses and
      severity of primary diagnosis at follow-up. Children in the bibliotherapy
      condition demonstrated a significant improvement over time in terms of child- and
      parent-reported anxiety levels. No differences were found between the two
      treatment conditions on any outcome measure. These results were maintained at 3-
      and 6-month follow-up. Although a pilot study, these data suggest that a
      bibliotherapy format of the intervention described may have potential merit. The
      implications for service delivery are discussed, as are the limitations of this
      research.

PMID- 19165539
TI  - Prevalence and correlates of mental disorders among adolescents in Italy: the
      PrISMA study.
AB  - BACKGROUND: While in the last 5 years several studies have been conducted in
      Italy on the prevalence of mental disorders in adults, to date no epidemiological
      study has been targeted on mental disorders in adolescents. METHOD: A two-phase
      study was conducted on 3,418 participants using the child behavior checklist/6-18
      (CBCL) and the development and well-being assessment (DAWBA), a structured
      interview with verbatim reports reviewed by clinicians. RESULTS: The prevalence
      of CBCL caseness and DSM-IV disorders was 9.8% (CI 8.8-10.8%) and 8.2% (CI 4.2
      12.3%), respectively. DSM-IV Emotional disorders were more frequently observed
      (6.5% CI 2.2-10.8%) than externalizing disorders (1.2% CI 0.2-2.3%). In girls,
      prevalence estimates increased significantly with age; furthermore, living with a
      single parent, low level of maternal education, and low family income were
      associated with a higher likelihood of suffering from emotional or behavioral
      problems. CONCLUSIONS: Approximately one in ten adolescents has psychological
      problems. Teachers and clinicians should focus on boys and girls living with a
      single parent and/or in disadvantaged socioeconomic conditions.

PMID- 19165540
TI  - Insights into the characteristics of mammalian cardiomyocyte terminal
      differentiation shown through the study of mice with a dysfunctional c-kit.
AB  - Mammalian cardiomyocytes withdraw from the cell cycle soon after birth. This
      process is called terminal differentiation. The c-kit, a receptor tyrosine
      kinase, is expressed on cardiomyocytes immediately after birth but for only a few
      days. In mice with genetic c-kit dysfunction, adult cardiomyocytes are
      phenotypically indistinguishable from those of wild type mice, except that they
      are capable of proliferation in vivo after acute pressure overload. This review
      explores the idea that postnatal cardiomyocyte differentiation and cell cycle
      withdrawal are distinct processes and that terminal differentiation may not
      simply be due to altered expression of genes that regulate the cell cycle but
      could involve c-kit induced epigenetic change.

PMID- 19165541
TI  - Laparoscopic accessory splenectomy: the value of perioperative localization
      studies.
AB  - BACKGROUND: Laparoscopic splenectomy is an effective treatment for many patients
      with immune thrombocytopenic purpura (ITP) who fail or relapse after treatment
      with steroids. Patients with an incomplete response to splenectomy and those who
      experience recurrence of symptoms should be evaluated for the presence of an
      accessory spleen. The clinical effectiveness of laparoscopic excision of an
      accessory spleen after a previous splenectomy for ITP has varied in different
      studies. Laparoscopic intraoperative identification of an accessory spleen can be
      difficult. The authors report their experience with laparoscopic accessory
      splenectomy (LAS) and the use of perioperative localization methods for this
      procedure. METHODS: This study reviewed seven consecutive patients who underwent
      LAS, after initial splenectomy failed to cure ITP, at a tertiary care center
      between April 9, 2003 and March 31, 2008. Demographics, diagnostic and
      localization studies, technical success, and the effect on thrombocytopenia were
      examined. The location of the accessory spleen also was recorded. A novel method
      for localizing accessory spleen was used. It consisted of preoperative computed
      tomography (CT)-guided injection of methylene blue at the accessory spleen's
      site, preoperative intravenous injection of 99m-technetium-labeled, heat-damaged
      red blood cells, or both. Intraoperatively, the dye was used for visual
      identification, and the gamma probe was used to aid in locating and confirming
      the presence of the accessory spleen in the excised specimen. RESULTS: Seven
      patients with recurrent ITP after initial failed splenectomy underwent LAS during
      the study period. Five of these patients had the initial splenectomy performed
      laparoscopically. All seven patients had successful laparoscopic removal of the
      accessory spleen based on a final pathologic examination. One patient required
      the second laparoscopic exploration with perioperative localization after a
      failed attempt without it. These perioperative localization methods were used in
      subsequent operations on other patients. These methods were found to be helpful
      in the intraoperative identification of the accessory spleens. The accessory
      spleens missed at initial splenectomy were found in unusual locations. Five of
      the seven patients had sustained improvement in platelet counts after LAS. One
      patient had a postoperative ileus that resolved with nonoperative management. No
      other complications or mortality was observed. CONCLUSION: The LAS procedure
      after previous splenectomy is feasible and safe. Perioperative localization
      methods aid in the intraoperative identification of an accessory spleen.
      Accessory spleens missed at initial splenectomy are generally found in unusual
      locations. Treatment of recurrent or unresolved ITP with LAS can be effective for
      some patients.

PMID- 19165542
TI  - The surface display of the alginate lyase on the cells of Yarrowia lipolytica for
      hydrolysis of alginate.
AB  - The alginate lyase structural gene (AlyVI gene) was amplified from plasmid pET24
      ALYVI carrying the alginate lyase gene from the marine bacterium Vibrio sp. QY101
      which is a pathogen of Laminaria sp. When the gene was cloned into the multiple
      cloning site of the surface display vector pINA1317-YlCWP110 and expressed in
      cells of Yarrowia lipolytica, the cells displaying the alginate lyase could form
      clear zone on the plate containing sodium alginate, indicating that they had high
      alginate lyase activity. The cells displaying alginate lyase can be used to
      hydrolyze poly-beta-D: -mannuronate (M) and poly-alpha-L: -guluronate (G) and
      sodium alginate to produce different lengths of oligosaccharides (more than
      pentasaccharides). This is the first report that the yeast cells displaying
      alginate lyase were used to produce different lengths of oligosaccharides from
      alginate.

PMID- 19165543
TI  - Silencing of TLR4 decreases liver tumor burden in a murine model of colorectal
      metastasis and hepatic steatosis.
AB  - BACKGROUND: The relationship between obesity and cancer has become of particular
      interest due to the rapidly growing prevalence of overweight individuals. Obesity
      predisposes individuals to the development of hepatic steatosis and is an
      independent risk factor for several neoplasms. Toll-like receptor 4 (TLR4) is the
      innate receptor for endotoxin, and steatotic livers are known to be sensitive to
      endotoxin. TLR4 signaling has been shown to have proneoplastic effects in vitro
      due to its effect on immune surveillance. Thus far, studies have predominantly
      focused on the effect of tumor-cell-derived TLR4 without regard to host TLR4
      signaling. RESULTS: In the present study we show that steatotic livers have
      increased expression of TLR4. Obese animals developed higher metastatic tumor
      burden in the liver than lean controls regardless of the presence or absence of
      intact host TLR4. After silencing TLR4 expression using RNAi in the mouse colon
      cancer cell line MC38, there was a significant decrease in metastatic tumor
      burden within the liver of obese animals. CONCLUSIONS: These findings demonstrate
      that steatotic livers have increased susceptibility to metastatic tumor growth
      and that silencing tumor cell TLR4 reduces metastatic tumor burden in steatotic
      liver.

PMID- 19165544
TI  - Infralevator lymphatic drainage of low-rectal cancers: preliminary results.
AB  - BACKGROUND: Some low-rectal cancers may spread into or recur in the inguinal
      lymph nodes despite optimal resection of the primary tumor. Hence, we
      hypothesized that lymphatic drainage of low-rectal malignancies may be
      inhomogeneous and that an extramesorectal route may be involved in at least some
      cases. The idea of our preliminary study was to analyze the potential lymphatic
      drainages in low-rectal cancer patients. METHODS: The first stage of the
      experiment included two consecutive low-rectal adenocarcinoma patients (free from
      inguinal lymph node metastases), in whom the lymphatics of the primary tumor were
      traced with Patentbalu dye. During the second stage the records of 206
      consecutive low-rectal cancer patients were analyzed for presence of inguinal
      lymph node metastases. RESULTS: An evaluation of specimens from two rectal cancer
      patients revealed extramesorectal lymphatic drainage of the primary tumor besides
      the mesorectal route. An analysis of 206 patients revealed six cases of inguinal
      node metastases. Median age of patients was 55 years. They were all diagnosed
      with rectal adenocarcinoma, T3 or T4 tumors with G2 or G3 grade. CONCLUSION: The
      demonstration of an alternative route of lymphatic drainage suggests that more
      radical surgical procedures are necessary for successful treatment of low-rectal
      cancers.

PMID- 19165545
TI  - Biology dictates prognosis following resection of gallbladder carcinoma:
      sometimes less is more.

PMID- 19165547
TI  - Low-level expression of Smad7 correlates with lymph node metastasis and poor
      prognosis in patients with pancreatic cancer.
AB  - BACKGROUND: Whether Smad7 acts as a tumor proliferation promoting factor or as a
      metastatic suppressor in human pancreatic cancer remains unclear. This study aims
      to determine the prognostic value of Smad7 in patients with pancreatic
      adenocarcinoma. METHODS: Surgical specimens obtained from 71 patients with
      pancreatic adenocarcinoma were immunohistochemically assessed for Smad7, Ki-67,
      MMP2, CD34, and Smad4 expression. The relationship between Smad7 expression and
      the clinicopathological characteristics of patients with pancreatic
      adenocarcinoma were also evaluated. RESULTS: Fifty-one of 71 specimens (71.8%)
      were Smad7 positive and 20 specimens were Smad7 negative. Negative expression of
      Smad7 correlated with lymph node metastasis, liver metastasis after surgery, and
      a poor survival rate (P = 0.0004, 0.0044, and 0.0003, respectively). We also
      found an inverse correlation between the expression of Smad7 and MMP2 (P =
      0.0189). Multivariate analysis revealed that Smad7 expression was an independent
      prognostic factor [hazard ratio (HR) 0.3902; 95% confidence interval (CI) 0.1839
      0.8277; P = 0.0142]. Furthermore, in both Smad4-negative and Smad4-positive
      groups, survival of patients with Smad7-positive tumors was significantly better
      than those with Smad7-negative tumors (both P < 0.0001). CONCLUSIONS: We conclude
      that low-level expression of Smad7 in pancreatic cancer is significantly
      associated with lymph node metastasis, high MMP2 expression, and poor prognosis.

PMID- 19165548
TI  - Primary care consultations about medically unexplained symptoms: how do patients
      indicate what they want?
AB  - BACKGROUND: Patients with medically unexplained physical symptoms (MUS) are often
      thought to deny psychological needs when they consult general practitioners (GPs)
      and to request somatic intervention instead. We tested predictions from the
      contrasting theory that they are transparent in communicating their psychological
      and other needs. OBJECTIVE: To test predictions that what patients tell GPs when
      they consult about MUS is related transparently to their desire for (1) emotional
      support, (2) symptom explanation and (3) somatic intervention. DESIGN:
      Prospective naturalistic study. Before consultation, patients indicated what they
      wanted from it using a self-report questionnaire measuring patients' desire for:
      emotional support, explanation and reassurance, and physical investigation and
      treatment. Their speech during consultation was audio-recorded, transcribed and
      coded utterance-by-utterance. Multilevel regression analysis tested relationships
      between what patients sought and what they said. PARTICIPANTS: Patients (N = 326)
      consulting 33 GPs about symptoms that the GPs designated as MUS. RESULTS:
      Patients who wanted emotional support spoke more about psychosocial problems,
      including psychosocial causes of symptoms and their need for psychosocial help.
      Patients who wanted explanation and reassurance suggested more physical
      explanations, including diseases, but did not overtly request explanation.
      Patients' wish for somatic intervention was associated only with their talk about
      details of such interventions and not with their requests for them. CONCLUSIONS:
      In general, patients with medically unexplained symptoms provide many cues to
      their desire for emotional support. They are more indirect or guarded in
      communicating their desire for explanation and somatic intervention.

PMID- 19165549
TI  - Intestinal stem cell organoid transplantation generates neomucosa in dogs.
AB  - BACKGROUND AND AIMS: Intestinal stem cell organoid transplantation generates
      functional intestinal neomucosa and has been used therapeutically to improve
      nutrient absorption and cure bile acid malabsorption in rats. We hypothesized
      that intestinal organoids can be harvested and transplanted to generate
      intestinal neomucosa in a large animal model. MATERIALS AND METHODS: In group 1,
      2-month old beagles (n = 6) underwent autotransplantation of intestinal organoids
      prepared from a segment of their own ileum. In group 2, intestinal organoids were
      harvested from fetuses and allotransplanted into 10-month old mother animals (n =
      4). Tissues were harvested after 4 weeks and analyzed by hematoxylin and eosin
      histology and fluorescent microscopy. RESULTS: Large numbers of viable organoids
      were harvested in both groups. In group 1, no neomucosal growth was identified in
      any of the engraftment sites after autotransplantation of juvenile organoids. In
      group 2, neomucosal growth with large areas of crypts and villi was identified in
      11 of 12 polyglycolic acid scaffolds after allotransplantation of fetal
      organoids. The neomucosa resembled normal canine mucosa in structure and
      composition. CONCLUSIONS: Intestinal stem cell organoid transplantation can be
      used to generate neomucosa in dogs. This is the first report of successful
      generation of intestinal neomucosa using intestinal stem cell organoid
      transplantation in a large animal model.

PMID- 19165550
TI  - Clinical remission in endoscope-guided pneumatic dilation for the treatment of
      esophageal achalasia: 7-year follow-up results of a prospective investigation.
AB  - BACKGROUND AND AIMS: Prospective, long-term reports and predictors of outcome of
      endoscope-guided pneumatic dilation are lacking in the literature. The aim of
      this prospective 7-year follow-up study is to report the efficacy of endoscope
      guided pneumatic dilation and determine the possible confounding factors related
      to remission. METHODS: Between January 1998 and June 2004, 32 patients were
      enrolled. Each patient was treated with endoscope-guided pneumatic dilation and
      followed-up at regular intervals for a median of 4.5 years. Remission was
      determined with the use of a structured interview and a previously described
      symptom score. Cumulative remission rate was analyzed by using the Kaplan-Meier
      method with assessment of symptom scores between grades before and after PD at 6
      weeks, 6 months, 1 year, and then every year after. Possible confounding factors
      related to the remissions were analyzed by Cox's proportional hazard model.
      RESULTS: Complete follow-up until August 2007 was obtained in 100% of all
      patients. Cumulative remissions were 1 year (86.7%), 2 years (86.7%), 3 years
      (80.0%), 4 years (76.5%), 5 years (72.9%), 6 years (61.7%), and 7 years (61.7%),
      respectively. Age is a relevant confounding factor to the remissions showing a
      worse outcome for those under 45 (p = 0.046). One esophageal perforation occurred
      (3.3%). CONCLUSIONS: Endoscope-guided PD itself is safe and modestly effective
      for up to 7 years investigations in current study. Older patients (>45 years)
      have favorable overall clinical remissions.

PMID- 19165551
TI  - Phospholipase Cbeta4 expression identifies a novel subset of unipolar brush cells
      in the adult mouse cerebellum.
AB  - Unipolar brush cells (UBCs) are glutamatergic cerebellar interneurons of the
      granular layer. Previous studies have shown that there are two distinct subsets
      of UBCs present in the mice cerebellar cortex: calcium-binding protein calretinin
      (CR) positive and metabotropic glutamate receptor (mGluR)1alpha positive. In this
      study, we identify phospholipase C (PLC) beta4 as an antigenic marker of a novel
      subset of UBCs. Double immunolabeling reveals that none of the CR+ subset
      expresses PLCbeta4. In contrast, most members of the mGluR1alpha subset also
      express PLCbeta4. In addition, 65% of the PLCbeta4+ subset does not express
      mGluR1alpha. Thus, there are three distinct UBC subsets in the mouse cerebellum:
      CR+/PLCbeta4-/mGluR1alpha-, PLCbeta4+/mGluR1alpha-/CR-, and
      mGluR1alpha+/PLCbeta4+/CR-. Each has a different topographical distribution, both
      between lobules and mediolaterally within the vermis. The development of PLCbeta4
      expression in UBCs is exclusively postnatal--first seen only at P12 and mature at
      about 3 weeks. A distinct subset of PLCbeta4+ UBCs is also present in primary
      cerebellar cultures.

PMID- 19165554
TI  - Lead poisoning: using transdisciplinary approaches to solve an ancient problem.
AB  - Conservation medicine examines the linkages among the health of people, animals,
      and the environment. Few issues illustrate this approach better than an
      examination of lead (Pb) toxicity. Lead is cheap and there is a long tradition of
      its use. But the toxic effects of Pb have also been recognized for many years. As
      a result, western societies have eliminated or greatly reduced many traditional
      uses of Pb, including many paints, gasoline, and solders because of threats to
      the health of humans and the environment. Legislation in several countries has
      eliminated the use of lead shot for hunting waterfowl. Despite these advances, a
      great many Pb products continue to be readily available. For example, wildlife
      agencies recognize that angling and shooting sports deposit thousands of tons of
      Pb into the environment each year. In recent years, our knowledge of the lethal
      and sublethal effects of Pb has grown dramatically. This discussion reviews the
      effects of lead on wildlife, humans, and domestic animals. It also discusses the
      importance of bringing together all interest groups to find safe alternatives, to
      develop new educational and policy initiatives, to eliminate many current uses of
      Pb, and to clean up existing problems.

PMID- 19165552
TI  - Friedreich's Ataxia: from the (GAA)n repeat mediated silencing to new promising
      molecules for therapy.
AB  - Friedreich's ataxia (FRDA) is a neurodegenerative disease due to a pathological
      expansion of a GAA triplet repeat in the first intron of the FXN gene encoding
      for the mitochondrial protein frataxin. The expansion is responsible for most
      cases of FRDA through the formation of a nonusual B-DNA structure and
      heterochromatin conformation that determine a direct transcriptional silencing
      and the subsequent reduction in frataxin expression. Among other functions,
      frataxin is an iron chaperone central for the assembly of iron-sulfur clusters in
      mitochondria; its reduction is associated with iron accumulation in mitochondria,
      increased cellular sensitivity to oxidative stress and cell damage. There is,
      nowadays, no effective therapy for FRDA and current therapeutic strategies mainly
      act to slow down the consequences of frataxin deficiency. Therefore, drugs that
      are able to increase the amount of frataxin are excellent candidates for a
      rational approach to FRDA therapy. Recently, several drugs have been assessed for
      their ability to increase the amount of cellular frataxin, including human
      recombinant erythropoietin, histone deacetylase inhibitors, and the PPAR-gamma
      agonists.

PMID- 19165553
TI  - Mercury and selenium in blood and epidermis of bottlenose dolphins (Tursiops
      truncatus) from Sarasota Bay, FL: interaction and relevance to life history and
      hematologic parameters.
AB  - Blood and epidermal biopsies from free-ranging Tursiops truncatus captured and
      released during either summer or winter health assessments in Sarasota Bay, FL,
      were evaluated for concentrations of mercury, selenium, stable isotopes (d(13)C
      and d(15)N), and blood glutathione peroxidase activity in conjunction with
      routine hematology and serum chemistry panels. Major objectives were to: 1)
      quantify and describe relationships among mercury, selenium, glutathione
      peroxidase, and stable isotopes of C and N in blood and epidermis; 2) elucidate
      major parameters that influence blood mercury and glutathione peroxidase
      activity; 3) relate measures of tissue mercury, selenium, and glutathione
      peroxidase to specific ecological, hematological, morphological, or life history
      parameters, including season, sex, age, and trophic level. Mercury in both
      tissues examined is almost exclusively methylmercury. Epidermal concentrations of
      mercury and selenium reflect their respective amounts in blood, albeit at several
      times blood concentrations of mercury. The strong association between blood
      mercury and serum selenium, in conjunction with a lack of significant correlation
      between blood mercury and glutathione peroxidase, implies that a substantial
      proportion of blood mercury is affiliated with another selenium-containing moiety
      or is related to recent dietary intakes (e.g., trophic level, intensive fish
      consumption). Circulating blood mercury may be described in terms of serum
      selenium concentration, along with interaction terms among serum selenium, blood
      d(15)N, and age. Current selenium concentrations in Sarasota Bay dolphins appear
      adequate for maintenance of blood glutathione peroxidase activity. However,
      dolphins evidently are subject to seasonal exacerbation of oxidative stress,
      which might render them more vulnerable to toxic effects of mercury.

PMID- 19165555
TI  - Association between fibromyalgia and sexual dysfunction in women.
AB  - The objective of the study was to review the association between fibromyalgia
      (FM) and sexual dysfunction in women and possible mechanisms of such association.
      PubMed, MEDLINE, and EMBASE databases (1950-2008) were searched for the key words
      "fibromyalgia", "chronic pain", "sexual dysfunction", "female", "sexuality",
      "depression", and "quality of life". All relevant articles in English and
      secondary references were reviewed. All reviewed studies showed that FM is
      associated with sexual dysfunction in women. The major findings were as follows:
      decreased sexual desire and arousal, decreased experience of orgasm, and
      increased pain with intercourse. FM, sexual dysfunction, and depression may be
      interrelated with the depressive mood responsible for desire and arousal
      problems. On the other hand, in FM patients, the threshold at which sensory input
      becomes painful is lower than normal that can explain pain on intercourse.
      Additional studies are needed to evaluate the casual relationship and mechanism
      of association between FM and sexual dysfunction in women.

PMID- 19165556
TI  - Is the Alifax Test-1TH useful to determine the Disease Activity Score (DAS28) in
      rheumatoid arthritis patients?
AB  - Treatment of rheumatoid arthritis (RA) is monitored with the disease activity
      score (DAS28), for which the erythrocyte sedimentation rate (ESR) is needed.
      Apart from the original gold standard method, other methods like the Alifax Test
      1TH apparatus are widely used in laboratory worldwide. We compared ESR values
      obtained by the Alifax Test-1Th apparatus and the gold standard method for 218 RA
      patients. We found a good correlation (r=0.87) between the Alifax Test-1TH
      results and the gold standard method. A good correlation (r=0.96) was also found
      for the DAS28 results obtained with both methods. The number of patients that
      were misclassified when the Alifax Test-1TH is used is reasonable for both the
      ESR (14.7%) and the DAS28 (10.6%). These results suggest that it may be useful to
      determine the ESR by the Alifax Test-1TH, with a DAS28 misclassification in less
      than 11% of the patients.

PMID- 19165557
TI  - Focal myocarditis mimicking myocardial infarction in a patient with rheumatoid
      arthritis.
AB  - Cardiovascular features in rheumatoid arthritis (RA) are common. However, RA
      associated with acute myocarditis is seldom described. Here, we report the case
      of a 58-year-old woman with rheumatoid arthritis and end stage renal disease who
      suffered chest tightness and diaphoresis during hemodialysis. The
      electrocardiogram showed ST elevations and the echocardiographic study revealed
      abnormalities of regional wall motion with moderate left ventricle dysfunction.
      Acute ST-elevation myocardial infarction was impressed according to clinical
      presentations and elevated cardiac enzymes. However, emergent coronary
      angiography revealed no significant coronary stenosis. Magnetic resonance imaging
      ultimately made the diagnosis of myocarditis. The patient improved gradually
      without immunosuppressive therapy. This case shows that conservative treatment is
      a feasible strategy for acute myocarditis in a patient with rheumatoid arthritis.

PMID- 19165558
TI  - Hemophagocytic syndrome in elderly patients with underlying autoimmune diseases.
AB  - In patients with autoimmune disease-associated hemophagocytic syndrome (AAHS),
      the clinical features may differ from hemophagocytic syndrome (HPS) of other
      etiologies, and new criteria for AAHS have been proposed. Since bone marrow (BM)
      circumstances are changed according to aging, here we reviewed retrospectively
      our cases with AAHS in elderly patients, including two systemic lupus
      erythematosus (SLE), three Evans syndrome, one rheumatoid arthritis (RA), one
      Hashimoto thyroiditis, and one autoimmune pancreatitis. Although only two SLE
      patients were diagnosed as HPS by the classical criteria, the remaining patients
      except one RA met the criteria for AAHS. Seven patients except one SLE patient
      showed good response to therapy and demonstrated positive autoantibodies to blood
      cells, lower serum ferritin levels, and increased erythroblastic islands in the
      BM. We consider the diagnosis of AAHS should be carefully made when macrophages
      phagocytosing blood cells are observed in BM smear without hyperferritinemia in
      elderly patients with autoimmune diseases.

PMID- 19165559
TI  - Nonbullous neutrophilic dermatosis: Sweet's syndrome, neonatal lupus
      erythematosus, or both?
AB  - We describe a 5-day-old infant who fulfilled the diagnostic criteria for Sweet's
      syndrome, and the concurrent histologic and autoantibody features supporting the
      diagnosis of neonatal lupus. To our knowledge, this is the youngest case of
      Sweet's syndrome reported in the literature. Importantly, our findings further
      support the hypothesis that lupus erythematosus should be considered in the
      differential diagnosis of a nonbullous neutrophilic dermatosis, as it may
      represent the initial manifestation of the disease.

PMID- 19165560
TI  - Prevalence of muzzle-rubbing and hand-rubbing behavior in wild chimpanzees in
      Mahale Mountains National Park, Tanzania.
AB  - In 1998, four chimpanzees in the Mahale Mountains National Park, Tanzania, were
      observed wiping their mouths with non-detached leaves or stalks of grass, or
      rubbing their mouths with a tree trunk or branch, especially while eating lemons.
      The number of mouth-wiping/rubbing individuals increased to 18 in 1999. By 2005,
      29 chimpanzees were documented wiping/rubbing their muzzles in this way. Although
      it is difficult to determine whether the chimpanzees acquired this behavior as a
      result of trial and error or social learning, the fact that chimpanzees at other
      sites perform this behavior with detached leaves or leafy twigs much more often
      than with intact items suggests the possibility that cleaning with intact plant
      parts at Mahale spread via social learning.

PMID- 19165561
TI  - Decreased plasma concentrations of adiponectin in patients with slow coronary
      flow.
AB  - Adiponectin has multiple protective effects on vascular endothelium through anti
      inflammatory and anti-atherogenic properties. Recent data suggested that
      endothelial activation and inflammation may contribute to the pathogenesis of
      slow coronary flow (SCF). Therefore, we investigated whether adiponectin plasma
      concentrations were decreased in patients with SCF compared to subjects with
      normal coronary flow. The study population consisted of 35 patients with
      angiographically documented SCF in all three coronary arteries and 35 sex- and
      age-matched cases with normal coronary flow. Coronary flow rates of all
      participants were determined by Thrombolysis in Myocardial Infarction (TIMI)
      frame count. Plasma adiponectin concentrations were measured by an enzyme-linked
      immunosorbent assay method using commercially available adiponectin kits. There
      were no statistically significant differences between the patients with SCF and
      the subjects with normal coronary flow in terms of demographic characteristics
      and cardiovascular risk factors (P>0.05). Plasma adiponectin concentrations of
      patients with SCF were found to be significantly lower than those with normal
      coronary flow (4.77+/-3.86 mg/ml vs 10.8+/-6.60 mg/ml, P=0.001, respectively).
      Plasma adiponectin levels were correlated significantly and inversely with mean
      TIMI frame count in patients with SCF (r= -0.441, P=0.008). Furthermore, the
      Receiver Operator Characteristics curve of adiponectin concentrations showed that
      an adiponectin <4.6 mg/ml is associated with SCF with a sensitivity of 68.6%,
      specificity of 82.9%, positive predictive value of 80.0%, and negative predictive
      value of 72.5%. Our findings suggest that endothelial inflammation may play a
      role in the pathogenesis of SCF phenomenon.

PMID- 19165562
TI  - Comparison of myocardial performance index obtained either by conventional
      echocardiography or tissue Doppler echocardiography in healthy subjects and
      patients with heart failure.
AB  - This study was planned to investigate the normal reference values of myocardial
      performance index (MPI) obtained by tissue Doppler echocardiography (TDE) and the
      agreement between MPI measured by TDE and conventional MPI measured by pulsed
      wave Doppler (PWD) in healthy subjects and patients with heart failure (HF). Two
      hundred and three patients with HF and 190 healthy subjects were enrolled in this
      study. Isovolumic contraction and relaxation time (ICT and IRT) and ejection time
      (ET) were measured from mitral inflow and left ventricular (LV) outflow. Tissue
      Doppler echocardiography recordings were obtained at the septal, lateral,
      inferior, and anterior of the mitral annulus and same time intervals were
      measured. Myocardial performance index was calculated. The functional capacity of
      the patients with HF was determined according to New York Heart Association
      classification. TDE-MPI values were higher than conventional PWD-MPI values in
      both groups (53%+/-8% vs 48%+/-11%, P<0.0001 in the healthy subjects; 84%+/-21%
      vs 72%+/-19%, P<0.0001 in the patients with HF). Moderate agreement was found
      between PWD-MPI and LV mean TDE-MPI in both groups. In identifying patients with
      moderately or severely decreased LV ejection fraction, TDE-MPI had higher cutoff
      values than conventional PWD-MPI, and TDE-MPI had higher specificity,
      sensitivity, negative predictive value, and diagnostic accuracy. In patients with
      HF, TDE-MPI had a stronger correlation with LV ejection fraction and functional
      capacity than did PWD-MPI. TDE-MPI is an alternative to conventional PWD-MPI in
      assessment of cardiac function. However, the higher MPI cutoff points should be
      considered when this method is used for the evaluation of cardiac function.

PMID- 19165563
TI  - Comparative effects of levosimendan and dobutamine on right ventricular function
      in patients with biventricular heart failure.
AB  - Severe heart failure represents a major source of morbidity and mortality. Poor
      right ventricular function is an independent prognostic marker for mortality in
      patients with chronic heart failure. In this study, levosimendan (L) and
      dobutamine (D) in patients with severe chronic biventricular failure were
      compared. Forty consecutive patients, who were judged for inotropic therapy by
      their primary physicians, with acutely decompensated systolic heart failure and
      having moderate-to-severe right ventricular dysfunction with right ventricular
      fractional area change of <or= 24%m were randomized to L and D in a 2:1 fashion.
      Echocardiographic parameters including tricuspid annular motion and clinical
      issues were considered. Mean age and sex distribution were not different between
      the two groups. After the infusion, ejection fraction improved and systolic
      pulmonary artery pressure decreased significantly in both arms. Longitudinal
      systolic function of tricuspid annulus improved significantly better in patients
      with L compared to patients with D (15%+/-12% vs. 2%+/-6% improvement, P<0.001).
      Furthermore, L improved both 24-h urine output and creatinine, whereas D showed
      only a small, but significant improvement in urine output without any improvement
      in the creatinine levels. Levosimendan seems to offer more beneficial effects
      compared to dobutamine in a specific group of patients with biventricular
      failure.

PMID- 19165564
TI  - Chronic systemic inflammation accompanies impaired ventricular diastolic
      function, detected by Doppler imaging, in patients with newly diagnosed systolic
      heart failure (Hellenic Heart Failure Study).
AB  - We sought to evaluate the relationship between plasma cytokine levels (sCD14,
      tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6) and tissue Doppler
      derived indices of left ventricular systolic and diastolic function in patients
      with newly diagnosed heart failure. We enrolled 101 consecutive patients (mean
      age 65+/-13 years) with newly diagnosed heart failure who were hospitalized in
      our institute. Echocardiographic assessment was performed in all patients during
      the third day of their initial hospitalization. The pulsed tissue Doppler imaging
      (TDI) of the systolic and diastolic function of mitral annulus was characterized
      by the systolic wave Smv, and the diastolic waves: Emv and Amv. Left atrial
      kinetic energy (LAKE), an index of left atrial function, was calculated using the
      equation 1/2 x LASV x 1.06 x Amv(2); where LASV is left atrial systolic volume.
      Furthermore the ratio E/Emv and the flow propagation velocity were also
      calculated; where E is the rapid mitral filling wave, detected by pulse Doppler.
      Soluble plasma levels of CD14, TNF-alpha, and IL-6 were measured in all patients
      during their third day of hospitalization. Linear regression analysis, after
      adjustment for sex, age, left ventricular ejection function, body mass index,
      arterial hypertension, smoking, physical activity, creatinine clearance, diabetes
      mellitus, and blood lipid levels, revealed that IL-6 levels were inversely
      associated with LAKE (b= - 5422.4+/-2031.5, P=0.03), Sm (b= -0.375+/-0.1,
      P=0.03), and flow propagation (b= -5.404+/-0.621, P=0.001). CD14 levels were
      inversely associated with flow propagation (b = -17.655+/-2.6, P=0.001), and
      positively associated with E/Emv ratio (b=2.58+/-3.6, P=0.002) and A/Amv ratio
      (b=0.629+/-0.6, P=0.04). TNF-alpha was inversely associated with Smv (b-1.189+/
      0.3, P=0.005). This study reveals that increased plasma levels of CD14, IL-6 and
      TNF-alpha are associated with impaired left atrial function and more advanced
      left ventricular diastolic and systolic dysfunction, in patients with newly
      diagnosed heart failure.

PMID- 19165566
TI  - Right atrial spontaneous echo contrast indicates a high incidence of perfusion
      defects in pulmonary scintigraphy in patients with atrial fibrillation.
AB  - This study investigated the relationship between right atrial SEC (RA-SEC) and
      silent pulmonary embolism (PE) in patients with nonvalvular atrial fibrillation
      (NVAF). Spontaneous echo contrast (SEC) within the cardiac chambers is associated
      with an increased risk of thromboembolism. However, most studies have examined
      the relationship between left atrial SEC and systemic thromboembolic disease.
      Transesophageal echocardiography (TEE) was performed in 210 patients with NVAF to
      assess a risk of thromboembolism. Right atrial SEC was detected in 37 patients,
      and 35 of these patients with RA-SEC and 29 patients without RA-SEC were enrolled
      in this study. However, patients with a history of symptomatic PE or deep vein
      thrombosis were excluded. Spontaneous echo contrast was diagnosed by TEE as the
      presence of smoke-like echoes that swirled in a circular pattern. PE was
      diagnosed by pulmonary scintigraphy. Thrombotic and thrombolytic parameters,
      including serum concentrations of plasmin-alpha-plasmin inhibitor complex (PIC),
      thrombin-antithrombin complex (TAT), D-dimer, and fibrinogen were measured in all
      patients. Left ventricular dimension, cardiac function, and hematologic
      parameters were similar in the two groups. Nevertheless, the incidence of
      perfusion defects in pulmonary scintigraphy was significantly higher in the group
      with RA-SEC (40%) than in the group without RA-SEC (7%; chi-square, P=0.006). The
      increased incidence of perfusion defects in pulmonary scintigraphy in patients
      with RA-SEC indicates that right atrial SEC may be a predictable factor at a high
      risk of PE.

PMID- 19165565
TI  - Alcohol septal ablation for obstructive hypertrophic cardiomyopathy: ultra-low
      dose of alcohol (1 ml) is still effective.
AB  - Echo-guided alcohol septal ablation (ASA) is an alternative treatment for highly
      symptomatic patients with obstructive hypertrophic cardiomyopathy (HOCM).
      Previous reports suggest that a low dose of alcohol (1.5-2 ml) is as effective as
      the classic dose (2-4 ml) used in the past. Because a larger infarct might be
      associated with a potential long-term risk, in this pilot study we wanted to
      determine whether an ultra-low dose of alcohol (1 ml) would be effective in the
      mid-term follow-up. Seventy patients (55+/-13 years, range 24-81 years, septum
      thickness <31 mm) with a highly symptomatic HOCM receiving maximum medical
      therapy were enrolled. Thirty-five consecutive patients (group I) have been
      treated with an ultra-low alcohol dose (1.0+/-0.1 ml) and compared with a control
      group II of 35 patients treated by the same medical team using the classic
      alcohol dose (2.5+/-0.8 ml) in the past. At 6-month follow-up, both groups of
      patients improved in dyspnea (2.9+/-0.6 vs 1.5+/-0.5 New York Heart Association
      [NYHA] class for group I; P<0.01, and 2.5+/-0.7 vs 1.4+/-0.4 NYHA class for group
      II; P<0.01) and angina (2.1+/-1 vs 0.6+/-0.8 Canadian Cardiovascular Society
      [CCS] class for group I; P<0.01, and 2.1+/-0.9 vs 0.7+/-0.7 CCS class for group
      II; P<0.01). There was a significant decrease in left ventricular (LV) ejection
      fraction (P<0.05), septum thickness (P<0.01), and LV outflow gradient (P<0.01) in
      both groups of patients. However, there was no significant difference with regard
      to the extent of symptomatic or echocardiographic changes and complications
      between both groups. These results suggest that the ultra-low dose of alcohol (1
      ml) is still effective in the treatment of the majority of HOCM patients without
      extreme septum hypertrophy (<31 mm).

PMID- 19165567
TI  - Left ventricular mass regression following implantation of MIRA bileaflet valves
      in patients with severe aortic stenosis.
AB  - The aim of this study was to evaluate the factors that determine the course of
      left ventricular mass regression in a homogeneous group of patients following
      aortic valve replacement by use of the mechanical Edwards MIRA bileaflet
      prosthesis. Furthermore, we examined if the 19-mm valve leads to an equally good
      outcome when compared with larger 21- and 23-mm valves. We included 79 patients
      (49 men) with a mean age of 65+/-9 years operated on for isolated aortic valve
      replacement with the MIRA valve prosthesis. The analyses included preoperative
      and postoperative echocardiograms during a follow-up of at least 18 months (995+/
      439 days) after valve surgery. Indication for valve replacement was aortic
      stenosis in 59 and combined disease (aortic stenosis and regurgitation) in 20
      patients. Concomitant coronary artery bypass grafting was performed in 28
      patients. Left ventricular mass index declined from 155.6+/-47 g/m(2) to 128.8+/
      35 g/m(2) (P<0.001) at final visit and normalized in 49% of the patients. Female
      sex and a preoperatively highly elevated left ventricular mass index were
      identified as risk factors for residual hypertrophy. However, age and valve size
      did not have a predictive value for completeness of left ventricular mass
      regression. This study supports the evidence that an extensive preoperative left
      ventricular hypertrophy results in an incomplete postoperative mass regression in
      patients with aortic bileaflet valves. It shows that the slightly elevated
      pressure gradient in MIRA 19-mm valves does not affect left ventricular mass
      regression.

PMID- 19165568
TI  - Ventricular energetics in aortic root replacement for annuloaortic ectasia with
      aortic regurgitation.
AB  - Aortic root replacement (Bentall operation) is the standard operation for
      patients who have lesions of the ascending aorta associated with aortic valve
      disease. We analyzed the mid-term results for left ventricular energetics after
      the Bentall operation for annuloaortic ectasia with aortic regurgitation. We
      measured left ventricular contractility (end-systolic elastance; Ees), afterload
      (effective arterial elastance; Ea), and efficiency (ventriculoarterial coupling;
      Ea/Ees, and the ratio of stroke work and pressure-volume area; SW/PVA) based on
      transthoracic echocardiography data before, after, and approximately 1 year after
      the Bentall operation in 15 patients with annuloaortic ectasia with aortic
      regurgitation. Left ventricular volume was calculated by the Teichholz M-mode
      method. Ees and Ea were approximated as follows: Ees=mean blood pressure/minimal
      left ventricular volume, and Ea=systolic blood pressure/(maximal left ventricular
      volume--minimal left ventricular volume). Ea/Ees and SW/PVA were then calculated.
      Left ventricular volume was normalized with body surface area. Ees increased
      after the Bentall operation and around 1 year later (from 2.17+/-1.09 to 3.92+/
      2.26 and 5.33+/-1.90 mmHg x m(2)/ml, P<0.001), thus resulting in an improvement
      in SW/PVA (from 68.8+/-8.2 to 70.9+/-9.5 and 74.7+/-5.2%, P=0.045). Ea also
      increased after the Bentall operation and 1 year later (from 1.77+/-0.61 to
      2.88+/-1.28 and 3.54+/-1.43 mmHg x m(2)/ml, P<0.001). The mid-term results for
      ventricular contractility and efficiency after the Bentall operation for
      annuloaortic ectasia with aortic regurgitation are excellent and satisfactory.

PMID- 19165569
TI  - Echocardiographic and electrocardiographic analyses of patients with severe motor
      and intellectual disabilities.
AB  - Severe motor and intellectual disabilities (SMID) syndrome is a heterogeneous
      group of disorders with severe physical disabilities and mental retardation.
      Higher incidence of sudden death is also known in these patients. However, little
      is known about the cardiovascular features of patients with SMID. We examine the
      patients with severe motor and intellectual disabilities using echocardiogram and
      clarify their characterization of ventricular function. We performed
      electrocardiographic and echocardiographic analyses in SMID patients. In all
      patients, two-dimensional echocardiography with tissue Doppler analysis in the
      pulsed Doppler mode was performed. Of 121 patients, 104 patients had abnormal
      findings: 81 had poor R-wave progression, and 15 patients had low-voltage QRS on
      ECG. These findings strongly correlated with the degree of physical disability.
      However, on echocardiography, most patients had LVEF in the normal range, while
      LV Tei indices were significantly higher (0.43 vs 0.31 cm/s) and left ventricular
      end-diastolic dimension significantly smaller than healthy controls (P<0.05 for
      each comparison). Patients had significantly decreased early diastolic tissue
      Doppler velocities at the lateral mitral (5.3 vs 6.7 cm/s), tricuspid (6.7 vs 9.2
      cm/s), and septal (5.9 vs 8.8 cm/s) annuli compared with controls (P<0.05 for
      each comparison). We show for the first time that SMID patients have low E/Ea
      ratios on tissue Doppler imaging while LV contractions are normal, suggesting the
      existence of latent diastolic dysfunction. This may be one of the reasons why the
      incidence of sudden death is higher in SMID patients.

PMID- 19165570
TI  - Altered expression of Na+ transporters at the mRNA level in rat normal and
      hypertrophic myocardium.
AB  - Intracellular Na(+) ([Na(+)](i)) regulation plays a crucial role in the
      structural, mechanical, and electrical properties of myocardium. It is assumed
      that the [Na(+)](i) handling system may differ not only between normal and
      diseased hearts but also regionally within a heart. To gain new insight
      concerning disease- and region-dependent differences in the [Na(+)](i)-regulatory
      system, we investigated mRNA expression of Na+ transporters, the principal
      determinants of [Na(+)](i). Nonischemic pressure-overloaded hypertrophy was
      created by suprarenal abdominal aortic constriction of 50% for 7 weeks. mRNA
      abundances of Na(+)-Ca(2+) exchanger (NCX1), Na(+)-H(+) exchanger (NHE1), Na(+)
      K(+)-2Cl(-) exchanger (NKCC1) and Na(+), K(+)-ATPase multigene family(alpha(1),
      alpha(2), alpha(3), and beta(1) isoforms) were measured by the real-time
      quantitative polymerase chain reaction method. mRNA abundance of all transporters
      mediating Na(+) influx (NCX1, NHE1, and NKCC1) was significantly upregulated as
      compared to normal. In contrast, Na(+)-efflux-mediating transporter (Na(+), K(+)
      ATPase) mRNA expression was unaltered between normal and hypertrophic hearts.
      Losartan, an angiotensin II AT1 receptor antagonist, significantly attenuated
      upregulation of Na(+)-influx-mediating transporters induced by aortic
      constriction. The onset of Na(+)-influx-mediating transporter upregulation
      occurred within 5 days following constriction. In normal and hypertrophied
      hearts, mRNA of all Na(+)-influx-mediating transporters was expressed in order of
      abundance as: apex > septum approximately free wall of left ventricles. A
      transmural gradient in expression was also evident in normal hearts (midcardium >
      endo- and epicardium), which was attenuated under hypertrophic development.
      Myocardial hypertrophy is associated with significant changes in the spatial
      distribution and expression levels of Na(+) transporters. The upregulation of Na
      influx transporters during hypertrophy may contribute to the remodeling process,
      modulate contractility and promote arrhythmias.

PMID- 19165571
TI  - Naxos disease presenting with ventricular tachycardia and troponin elevation.
AB  - Naxos disease is a recessively inherited stereotype association of arrhythmogenic
      cardiomyopathy with a cutaneous phenotype, characterized by peculiar woolly hair
      and palmoplantar keratoderma. The cardiomyopathy clinically manifests by
      adolescence and the symptomatic presentation is usually with syncope and/or
      sustained ventricular tachycardia of left bundle branch block configuration. We
      report the case of a 43-year-old man without any history of heart disease who was
      admitted to the hospital because of an episode of sustained ventricular
      tachycardia and troponin I elevation, in the absence of coronary artery disease.
      Diagnostic workup, including genetic assessment, revealed Naxos disease as the
      underlying cause. In this case, acute myocarditis seems to be the most plausible
      explanation for the nonischemic myocardial injury.

PMID- 19165572
TI  - Regression of a thrombosed persistent sciatic artery aneurysm.
AB  - A 79-year-old woman who had a previous history of sudden onset of pain and
      coldness of her right leg was referred to our hospital. There were no palpable
      right popliteal and pedal pulses with the ankle-brachial pressure index being
      0.63. Computed tomography showed a 2.6-cm diameter right buttock mass which had a
      continuation from the right internal iliac artery that entered the posterior
      thigh and continued to the popliteal artery. It was diagnosed as thrombosed right
      persistent sciatic artery (PSA) aneurysm. She was treated medically with
      intravenous and oral antiplatelets, and was left with no right leg symptoms.
      Follow-up CT obtained after 3 years from onset demonstrated that the diameter of
      the PSA aneurysm diminished from 2.6 to 1.2 cm. It is suggested that a patient
      who had the occluded complete type PSA aneurysm with no critical leg ischemia,
      local compression, or rupture can be observed without surgery. However, careful
      follow-up of the patient is essential.

PMID- 19165573
TI  - A new technique to avoid the intraoperative complications of septal myectomy in
      patients with obstructive hypertrophic cardiomyopathy.
AB  - Although transaortic septal myectomy in obstructive hypertrophic cardiomyopathy
      (OHC) is accepted as a safe procedure, it may end up with serious peroperative
      complications. We developed a practical method to avoid this unfavorable outcome
      by using a 20-cc syringe body. We believe this apparatus will provide safe and
      effective septal myectomy procedures without additional cost.

PMID- 19165574
TI  - Antifreeze glycopeptide analogues: microwave-enhanced synthesis and functional
      studies.
AB  - Antifreeze glycoproteins enable life at temperatures below the freezing point of
      physiological solutions. They usually consist of the repetitive tripeptide unit (
      Ala-Ala-Thr-) with the disaccharide alpha-D-galactosyl-(1-3)-beta-N-acetyl-D
      galactosamine attached to each hydroxyl group of threonine. Monoglycosylated
      analogues have been synthesized from the corresponding monoglycosylated threonine
      building block by microwave-assisted solid phase peptide synthesis. This method
      allows the preparation of analogues containing sequence variations which are not
      accessible by other synthetic methods. As antifreeze glycoproteins consist of
      numerous isoforms they are difficult to obtain in pure form from natural sources.
      The synthetic peptides have been structurally analyzed by CD and NMR spectroscopy
      in proton exchange experiments revealing a structure as flexible as reported for
      the native peptides. Microphysical recrystallization tests show an ice
      structuring influence and ice growth inhibition depending on the concentration,
      chain length and sequence of the peptides.

PMID- 19165575
TI  - Curcumin attenuates oxidative damage in animals treated with a renal carcinogen,
      ferric nitrilotriacetate (Fe-NTA): implications for cancer prevention.
AB  - Curcumin (diferuloylmethane), a biologically active ingredient derived from
      rhizome of the plant Curcuma longa, has potent anticancer properties as
      demonstrated in a plethora of human cancer cell lines/animal carcinogenesis model
      and also acts as a biological response modifier in various disorders. We have
      reported previously that dietary supplementation of curcumin suppresses renal
      ornithine decarboxylase (Okazaki et al. Biochim Biophys Acta 1740:357-366, 2005)
      and enhances activities of antioxidant and phase II metabolizing enzymes in mice
      (Iqbal et al. Pharmacol Toxicol 92:33-38, 2003) and also inhibits Fe-NTA-induced
      oxidative injury of lipids and DNA in vitro (Iqbal et al. Teratog Carcinog
      Mutagen 1:151-160, 2003). This study was designed to examine whether curcumin
      possess the potential to suppress the oxidative damage caused by kidney-specific
      carcinogen, Fe-NTA, in animals. In accord with previous report, at 1 h after Fe
      NTA treatment (9.0 mg Fe/kg body weight intraperitoneally), a substantial
      increased formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts in
      renal proximal tubules of animals was observed. Likewise, the levels of 8-hydroxy
      2'-deoxyguanosine (8-OHdG) and protein reactive carbonyl, an indicator of protein
      oxidation, were also increased at 1 h after Fe-NTA treatment in the kidneys of
      animals. The prophylactic feeding of animals with 1.0% curcumin in diet for 4
      weeks completely abolished the formation of (i) HNE-modified protein adducts,
      (ii) 8-OHdG, and (iii) protein reactive carbonyl in the kidneys of Fe-NTA-treated
      animals. Taken together, our results suggest that curcumin may afford substantial
      protection against oxidative damage caused by Fe-NTA, and these protective
      effects may be mediated via its antioxidant properties. These properties of
      curcumin strongly suggest that it could be used as a cancer chemopreventive
      agent.

PMID- 19165576
TI  - The phosphorylation of SEPT2 on Ser218 by casein kinase 2 is important to
      hepatoma carcinoma cell proliferation.
AB  - SEPT2 plays an important role in cell division through its effect on
      cytoskeletons. It is a GTP-binding protein and can also form filament with SEPT6
      and SEPT7. Knockdown of SEPT2, 6, and 7 causes stress fibers to disintegrate and
      then cells lose polarity and divide abnormally. Increasing evidence has shown
      that septins are related to the regulation of cell proliferation. In this study,
      the expression of SEPT2 was first identified to be up-regulated in human hepatoma
      carcinoma cells (HCC). In addition, SEPT2 was found to be phosphorylated on
      Ser218 by casein kinase 2 (CK2), which was also overexpressed in HCC. By
      overexpressing SEPT2 and its S218A mutant in SMMC7721 and L02 cell lines, we
      confirmed that the phosphorylation of SEPT2 on Ser218 by CK2 was crucial to the
      proliferation of HCC. These results suggest that SEPT2 might be a promising
      target for liver cancer therapy.

PMID- 19165577
TI  - Hippocalcin, new Ca(2+) sensor of a ROS-GC subfamily member, ONE-GC, membrane
      guanylate cyclase transduction system.
AB  - Hippocalcin is a member of the neuronal Ca(2+) sensor protein family. Among its
      many biochemical functions, its established physiological function is that via
      neuronal apoptosis inhibitory protein it protects the neurons from Ca(2+)-induced
      cell death. The precise biochemical mechanism/s, through which hippocalcin
      functions, is not clear. In the present study, a new mechanism by which it
      functions is defined. The bovine form of hippocalcin (BovHpca) native to the
      hippocampus has been purified, sequenced, cloned, and studied. The findings show
      that there is the evolutionary conservation of its structure. It is a Ca(2+)
      sensor of a variant form of the ROS-GC subfamily of membrane guanylate cyclases,
      ONE-GC. It senses physiological increments of Ca(2+) with a K(1/2) of 0.5 microM
      and stimulates ONE-GC or ONE-GC-like membrane guanylate cyclase. The Hpca
      modulated ONE-GC-like transduction system exists in the hippocampal neurons. And
      hippocalcin-modulated ONE-GC transduction system exists in the olfactory receptor
      neuroepithelium. The Hpca-gene knock out studies demonstrate that the portion of
      this is about 30% of the total membrane guanylate cyclase transduction system.
      The findings establish Hpca as a new Ca(2+) sensor modulator of the ROS-GC
      membrane guanylate cyclase transduction subfamily. They support the concept on
      universality of the presence and operation of the ROS-GC transduction system in
      the sensory and sensory-linked neurons. They validate that the ROS-GC
      transduction system exists in multiple forms. And they provide an additional
      mechanism by which ROS-GC subfamily acts as a transducer of the Ca(2+) signals
      originating in the neurons.

PMID- 19165578
TI  - A turning point for blood-brain barrier modeling.

PMID- 19165580
TI  - Editorial-special section honoring N.A. Peppas.

PMID- 19165579
TI  - The science of USP 1 and 2 dissolution: present challenges and future relevance.
AB  - Since its inception, the dissolution test has come under increasing levels of
      scrutiny regarding its relevance, especially to the correlation of results to
      levels of drug in blood. The technique is discussed, limited to solid oral dosage
      forms, beginning with the scientific origins of the dissolution test, followed by
      a discussion of the roles of dissolution in product development, consistent batch
      manufacture (QC release), and stability testing. The ultimate role of dissolution
      testing, "to have the results correlated to in vivo results or in vivo in vitro
      correlation," is reviewed. The recent debate on mechanical calibration versus
      performance testing using USP calibrator tablets is presented, followed by a
      discussion of variability and hydrodynamics of USP Apparatus 1 and Apparatus 2.
      Finally, the future of dissolution testing is discussed in terms of new
      initiatives in the industry such as quality by design (QbD), process analytical
      technology (PAT), and design of experiments (DOE).

PMID- 19165581
TI  - Assessing ADHD-related family stressors with the Disruptive Behavior Stress
      Inventory (DBSI): a replication and extension.
AB  - The Disruptive Behavior Stress Inventory (DBSI) was developed to provide
      information related to the occurrence and severity of stressors that result from
      having a child with ADHD. Data provided in the initial 2002 study by Johnson and
      Reader (Journal of Clinical Psychology in Medical Settings, 9, 51-62) provided
      good preliminary support for the reliability of the DBSI, as well the ability of
      the scale scores to differentiate primary caregivers of children with and without
      a history of ADHD. The present study was an attempt to replicate major findings
      of the 2002 study using an additional larger sample and extend it by conducting
      item-level analyses to determine the degree to which individual DBSI items
      differentiate primary caregivers of children with and without a history of ADHD.
      Results provided additional support for the reliability and validity of the DBSI
      by replicating major findings from the 2002 study and further suggesting that a
      large majority of the 40 items individually differentiate between primary
      caregivers of children with and without a history of ADHD.

PMID- 19165582
TI  - "Diabetes and literacy: negotiating control through artifacts of medicalization".
AB  - My experience with the California Department of Motor Vehicles offers a case to
      explore how bureaucratic institutions monitor, classify, and control individuals.
      By examining artifacts created for and used by the DMV through the lens of
      literacy studies, I discuss the variety of rhetorical strategies used in each
      document and the effects and implications of those strategies, for example on
      subjectivity or identity, and move beyond the language of the artifacts
      themselves to attend to how they are invested with power in the management and
      control of populations.

PMID- 19165583
TI  - Feeding...being fed: poetry and commentary.

PMID- 19165584
TI  - Molecular cloning, sequencing, and expression of a L -glutamine D-fructose 6
      phosphate amidotransferase gene from Volvariella volvacea.
AB  - Using 3'-RACE and 5'-RACE, we have cloned and sequenced the genomic gene and
      complete cDNA encoding L: -glutamine D: -fructose 6-phosphate amidotransferase
      (GFAT) from the edible straw mushroom, Volvariella volvacea. Gfat contains five
      introns, and encodes a predicted protein of 697 amino acids that is homologous to
      other reported GFAT sequences. Southern hybridization indicated that a single
      gfat gene locus exists in the V. volvacea genome. Recombinant native V. volvacea
      GFAT enzyme, over-expressed using Escherichia coli and partially purified, had an
      estimated molecular mass of 306 kDa and consisted of four equal-sized subunits of
      77 kD. Reciprocal plots revealed K (m) values of 0.55 and 0.75 mM for fructose 6
      phosphate and L: -glutamine, respectively. V. volvacea GFAT activity was
      inhibited by the end-product of the hexosamine pathway, UDP-GlcNAc, and by the
      glutamine analogues N (3)-(4-methoxyfumaroyl)-L: -2,3-diaminopropanoic acid and 2
      amino-2-deoxy-D: -glucitol-6-phosphate.

PMID- 19165585
TI  - Beyond interstitial lung disease: the rapidly evolving role of Calgranulin B as a
      biomarker of systemic malignancies.

PMID- 19165586
TI  - Temperament as a predictor of symptomotology and adaptive functioning in
      adolescents with high-functioning autism.
AB  - Variation in temperament is characteristic of all people but is rarely studied as
      a predictor of individual differences among individuals with autism. Relative to
      a matched comparison sample, adolescents with High-Functioning Autism (HFA)
      reported lower levels of Surgency and higher levels of Negative Affectivity.
      Variability in temperament predicted symptomotology, social skills, and social
      emotional outcomes differently for individuals with HFA than for the comparison
      sample. This study is unique in that temperament was measured by self-report,
      while all outcome measures were reported by parents. The broader implications of
      this study suggest that by identifying individual variability in constructs, such
      as temperament, that may influence adaptive functioning, interventions may be
      developed to target these constructs and increase the likelihood that individuals
      with HFA will achieve more adaptive life outcomes.

PMID- 19165587
TI  - Corpus callosum volume and neurocognition in autism.
AB  - The corpus callosum has recently been considered as an index of interhemispheric
      connectivity. This study applied a novel volumetric method to examine the size of
      the corpus callosum in 32 individuals with autism and 34 age-, gender- and IQ
      matched controls and to investigate the relationship between this structure and
      cognitive measures linked to interhemispheric functioning. Participants with
      autism displayed reductions in total corpus callosum volume and in several of its
      subdivisions. Relationships were also observed between volumetric alterations and
      performance on several cognitive tests including the Tower of Hanoi test. These
      findings provide further evidence for anatomical alterations in the corpus
      callosum in autism, but warrant additional studies examining the relationship of
      this structure and specific measures of interhemispheric connectivity.

PMID- 19165588
TI  - Tomato yellow leaf curl Thailand virus-[Y72] from Yunnan is a monopartite
      begomovirus associated with DNAbeta.
AB  - Previous studies have shown that isolates of tomato yellow leaf curl Thailand
      virus (TYLCTHV) originated from Thailand are bipartite begomoviruses, while all
      the seven TYLCTHV isolates found in China are associated with DNAbeta molecules.
      In this study, infectious clones of TYLCTHV isolate Y72 (TYLCTHV-[Y72]) and its
      DNAbeta were constructed to verify the bipartite or monopartite nature of
      TYLCTHV. Agroinoculation showed that TYLCTHV-[Y72] alone was able to induce
      significant symptoms in Nicotiana benthamiana, Nicotiana glutinosa, and Solanum
      lycopersicum plants, but co-inoculation with its associated satellite DNAbeta
      produced more severe symptoms, which is similar to tobacco curly shoot virus.
      Southern blot results showed that TYLCTHV DNAbeta could increase the virus
      accumulation in systemically infected tissues. Thus, TYLCTHV-[Y72] is a
      monopartite begomovirus, which may represent an evolutionary intermediate between
      the begomoviruses requiring DNAbeta and begomoviruses dispensable of DNAbeta.

PMID- 19165589
TI  - Hyperactivity, impulsivity, inattention (HIA) and conduct problems among African
      American youth: the roles of neighborhood and gender.
AB  - This study replicated and extended prior research by examining neighborhood
      context as a moderator of the relation between the constellation of
      hyperactivity, impulsivity, and attention (HIA) difficulties and conduct problems
      among African American youth (11-16 years old; 55% girls) from single mother
      homes (N = 193). Using audio computer-assisted interview (ACASI) software, mother
      child dyads provided ratings of HIA difficulties and two domains of conduct
      problems: aggression and rule-breaking. In addition, both subjective (mother
      report) and objective (census data) indices of neighborhood context were
      assessed. Findings revealed that both subjective and objective indices of
      neighborhood context moderated the relation between HIA and conduct problems, but
      the pattern of moderation differed depending on the index and combination of
      reporters. Future research directions and implications of the findings are
      discussed.

PMID- 19165590
TI  - How are traits related to problem behavior in preschoolers? Similarities and
      contrasts between temperament and personality.
AB  - The lack of empirical research relating temperament models and personality
      hinders conceptual integration and holds back research linking childhood traits
      to problem behavior or maladjustment. This study evaluates, within a sample of
      443 preschoolers, the relationships between children's maladaptation and traits
      measured by three temperament models (Thomas and Chess, Buss and Plomin, and
      Rothbart), and a Five-Factor based personality model. Adequate reliabilities and
      expected factor structures are demonstrated for most scales. A joint principal
      component analysis combining 28 temperament and 18 personality scales indicates a
      six-factor model, distinguishing Sociability, Activity, Conscientiousness,
      Disagreeableness, Emotionality, and Sensitivity. Regression analyses reveal that
      although single temperament and personality scales explain from 23% to 37% of
      problem behavior variance, the six components explain from 41% to 49% and provide
      a clearer differentiation among CBCL-problem scales. This age-specific taxonomy
      refines and corroborates conclusions based on narrative reviews and furnishes a
      more balanced view of trait-maladjustment relationships.

PMID- 19165591
TI  - Assessment of relevant parenting factors in families of clinically anxious
      children: the Family Assessment Clinician-rated Interview (FACI).
AB  - OBJECTIVE: Research on child and adolescent anxiety disorders has seen a surge in
      investigations of parenting factors potentially associated with their etiology.
      However, many of the well-established parenting measures are limited by over
      reliance on self-report or lengthy behavioral observation procedures. Such
      measures may not assess factors most salient to anxiety etiology, since most
      family functioning measures were not originally developed for this purpose. The
      Family Assessment Clinician Interview (FACI) was developed as a clinician
      administered interview of parent and family factors associated with child and
      adolescent anxiety. The present study is the first to investigate the
      psychometric properties of the FACI. METHOD: Using a clinical sample of 65
      children with various anxiety disorders, and their parents, inter-rater
      reliability, convergent validity and associations with child-reported and
      clinician-evaluated anxiety severity were examined. RESULTS: suggest that the
      FACI has good to excellent inter-rater reliability with kappas ranging from 0.79
      to 1.0 across FACI scales and subscales. Some evidence of convergent validity
      with relevant portions of the Family Environment Scale was observed, although the
      latter findings varied by respondent (mother versus father). The Family
      Warmth/Closeness subscale of the FACI was consistently associated with increased
      child anxiety symptoms. Contrary to expectations, higher levels of parental
      expectations were associated with lower levels of child anxiety. CONCLUSION:
      Results suggest that the FACI is a promising measure of family anxiety constructs
      that may be useful in both research and clinical settings.

PMID- 19165592
TI  - One-year follow-up of family versus child CBT for anxiety disorders: Exploring
      the roles of child age and parental intrusiveness.
AB  - OBJECTIVE: To compare the relative long-term benefit of family-focused cognitive
      behavioral therapy (FCBT) and child-focused cognitive behavioral therapy (CCBT)
      for child anxiety disorders at a 1-year follow-up. METHOD: Thirty-five children
      (6-13 years old) randomly assigned to 12-16 sessions of family-focused CBT (FCBT)
      or child-focused CBT (CCBT) participated in a 1-year follow-up assessment.
      Independent evaluators, parents, and children rated anxiety and parental
      intrusiveness. All were blind to treatment condition and study hypotheses.
      RESULTS: Children assigned to FCBT had lower anxiety scores than children
      assigned to CCBT on follow-up diagnostician- and parent-report scores, but not
      child-report scores. Exploratory analyses suggested the advantage of FCBT over
      CCBT may have been evident more for early adolescents than for younger children
      and that reductions in parental intrusiveness may have mediated the treatment
      effect. CONCLUSION: FCBT may yield a stronger treatment effect than CCBT that
      lasts for at least 1 year, although the lack of consistency across informants
      necessitates a circumspect view of the findings. The potential moderating and
      mediating effects considered in this study offer interesting avenues for further
      study.

PMID- 19165593
TI  - Factor structure and psychometric properties of the Multidimensional Anxiety
      Scale for Children in an African American adolescent sample.
AB  - The current study examined the psychometric properties and factor structure of
      the Multidimensional Anxiety Scale for Children (MASC) among a community sample
      of 118 African American students (58 females; ages 14-19 years; mean age = 15.79)
      in an urban, parochial high school. Adolescents completed the MASC and several
      other self-report measures of anxiety, perceived competence, and symptoms of
      ADHD. The original MASC total and subscale mean scores were comparable to data
      reported in previous studies utilizing community samples of youth, though
      measures of internal consistency were lower. Factor analytic results supported a
      three factor solution (i.e., social anxiety, physical symptoms, harm avoidance)
      which accounted for 23.84% of the variance. While there was overlap in the
      underlying structure of anxiety between the original MASC publication and the
      current sample, items reflecting separation anxiety did not emerge as a separate
      factor. As expected, the MASC total score was positively correlated with measures
      of anxiety and perceived competence but unrelated to measures of hyperactivity.
      This study represents an important first step toward establishing more
      comprehensive age, race, and gender norms for the MASC.

PMID- 19165594
TI  - Infant temperament in Russia, United States of America, and Israel: differences
      and similarities between Russian-speaking families.
AB  - The present study addresses cross-cultural differences between infants born to
      families of Russian immigrants in USA and Israel, as well as Russian families
      residing in Russia, with the emphasis on evaluating the impact of immigration and
      acculturation. Community samples of primary caregivers of infants between 3 and
      12 months of age were recruited and asked to complete temperament (IBQ-R) and
      acculturation (SAM) questionnaires. Results support our hypotheses that cultural
      influences contribute to shaping infant temperament, in so far as differences
      between the samples of infants were found in Perceptual Sensitivity and Low
      Intensity Pleasure domains of temperament. Although, a number of temperament
      scales did not significantly correlate with the degree of parents' acculturation,
      different patterns of correlations emerged for Russian-Israeli and for Russian
      American samples.

PMID- 19165595
TI  - Breast cancer risk in relation to the joint effect of BRCA mutations and diet
      diversity.
AB  - It has been suggested that gene-environment interaction is related to the risk of
      cancer. To evaluate departure from multiplicative effects between BRCA mutations
      and diet diversity in breast cancer (BC), a case-only study was carried out in a
      French-Canadian population including 738 patients with incident primary BC
      comprising 38 BRCA mutation carriers. Diet diversity was assessed using a
      validated food frequency questionnaire. Unconditional logistic regression
      analysis was performed to assess case-only odds ratio (COR) and 95% confidence
      interval (CI) while adjusting for age, body mass index, smoking, hormonal
      replacement therapy, and total energy intake. Ours results reveal a strong and
      significant interaction between BRCA mutations and vegetable and fruit diversity
      (COR = 0.27; 95%CI = 0.10-0.80; P = 0.03) when comparing the upper to the lower
      quartiles. The estimates for departure from multiplicative effects between BRCA
      mutations and total or other food groups' diversity were not supportive of the
      idea of a gene-environment interaction. The results of this study suggest that
      the combination of BRCA mutations and vegetable and fruit diversity may be
      associated with a reduced risk of BC.

PMID- 19165596
TI  - Serotonin syndrome as a complication of fentanyl sedation during
      esophagogastroduodenoscopy.

PMID- 19165597
TI  - Characterization of the gastric cardia in volunteers from the general population.
      Type of mucosa, Helicobacter pylori infection, inflammation, mucosal
      proliferative activity, p53 and p21 expression, and relations to gastritis.
AB  - The aim of this research was to characterize the mucosa of the gastric cardia in
      relation to infection with Helicobacter pylori and the occurrence of chronic
      gastritis in other parts of the stomach in a sample of the general population. In
      this study, 80 adult volunteers underwent esophagogastroscopy with biopsies from
      the gastric cardia, corpus, and antrum. Gastritis was classified according to the
      Sydney system. Chronic gastritis (cardia excepted) was diagnosed in 35 subjects,
      30 with H. pylori infection. Epithelial proliferative activity (Ki-67), p53- and
      p21 expression were examined quantitatively with cell counting after
      immunohistochemical stainings. Esophagitis was diagnosed macroscopically. Fourty
      eight subjects had cardia-type and 32 corpus-type mucosa in the anatomical
      cardia. The prevalence of esophagitis (nine cases) did not differ between these
      groups. Carditis was more prevalent among subjects with cardia-type mucosa (73
      vs. 28%, P < 0.0001). H. pylori was present in 48% of those with cardia-type and
      25% of those with corpus-type mucosa (P = 0.06). Of the 44 subjects with
      carditis, 31 had H. pylori in this location. The group with H. pylori infection
      had significantly higher mucosal proliferative activity when compared to
      uninfected subjects. Among the subjects with H. pylori-associated carditis, more
      p53-positive epithelial cells were detected compared to both the non-infected
      group (P = 0.0004) and to subjects with non-H. pylori-associated carditis (P =
      0.03). In subjects with cardia-type mucosa, and both carditis and gastritis, the
      degree of chronic inflammation was higher in the cardia compared to the corpus
      and antrum and the p53 expression was significantly higher in the cardia compared
      to the corpus, but similar to that in the antrum. The proliferative activity was
      significantly higher in the antrum compared to the cardia and corpus,
      respectively. In conclusion, H. pylori infection, carditis, and increased p53
      expression are more common in subjects with cardia- than corpus-type mucosa in
      the gastric cardia. Carditis is mainly related to H. pylori infection. There are
      some differences regarding inflammation, proliferative activity, and p53
      expression between the cardia and other regions of the stomach, yet the
      significance of these differences remains to be clarified.

PMID- 19165598
TI  - Incidence and etiology of overt gastrointestinal bleeding in adult patients with
      aplastic anemia.
AB  - Patients with thrombocytopenia caused by various neoplastic and primary bone
      marrow diseases are susceptible to major hemorrhage. There are few reports
      addressing the incidence and outcome of gastrointestinal (GI) bleeding in
      patients with aplastic anemia characterized by long-standing thrombocytopenia. We
      sought to retrospectively determine the incidence, etiology, clinical outcomes,
      and risk factors associated with overt GI bleeding in patients with aplastic
      anemia. We analyzed the medical records of 508 patients with aplastic anemia
      after excluding patients below 15 years of age or those who underwent stem cell
      transplantation between January 1, 2002, and December 31, 2007. A total of 32
      patients developed overt GI bleeding during this period. We evaluated the site,
      etiology, outcomes, and major risk factors in these patients who developed GI
      bleeding episodes. The incidence of GI bleeding was 6.3% (32 of 508 patients) in
      adult patients with aplastic anemia. The incidence increased to 12.6% (28 of 222
      patients) in patients with severe disease. One patient died from massive GI
      bleeding. Bleeding sites included the esophagus (two patients, 6.3%), stomach
      (five, 16.3%), duodenum (two, 6.3%), small intestine (five, 15.6%), large
      intestine (seven, 21.6%), and unknown site (11, 34.4%). Lower GI bleeds mainly
      caused by neutropenic enterocolitis (NEC) and solitary ulcer developed more
      frequently than upper GI bleeds. The major risk factors for GI bleeding included
      old age (P = 0.004, odds ratio (OR) = 1.039), severe aplastic anemia (P < 0.001,
      OR = 11.934), non-response to therapy (P = 0.001, OR = 5.652), and major bleeding
      history in another organ (P < 0.001, OR = 6.677). Overt GI bleeding in patients
      with aplastic anemia more frequently develops in the lower tract than in the
      upper tract. The risk of GI bleeding is higher in patients with the following
      risk factors: older age, severe disease, poor response to treatment, and major
      bleeding history in another organ.

PMID- 19165599
TI  - Effects of ethanol and its metabolites on human pancreatic stellate cells.
AB  - Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic inflammation
      and fibrosis. In the pancreas, in addition to oxidative metabolism, ethanol can
      be metabolized by esterification with fatty acids to form fatty acid ethyl esters
      such as palmitic acid ethyl ester (PAEE). We here examined the effects of ethanol
      (at 20 or 50 mM), acetaldehyde (at 200 microM), or PAEE (at 100 microM), on PSCs
      functions. PSCs did not express mRNAs for pancreatic triglyceride lipase and
      carboxyl ester lipase. Ethanol and acetaldehyde, but not PAEE, induced production
      of procollagen type I C-peptide. Ethanol, but not acetaldehyde or PAEE, induced
      interleukin-8 production. PAEE activated activator protein-1, but not nuclear
      factor kappaB. In addition, PAEE activated extracellular signal-regulated kinase,
      c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. Specific
      activation of signal transduction pathways and cell functions by ethanol and its
      metabolites may play a role in alcohol-induced pancreatic injury.

PMID- 19165600
TI  - A new bioreactor for the development of tissue-engineered heart valves.
AB  - This paper reports the design, manufacturing, and characterization of a new
      bioreactor dedicated to the development of tissue-engineered heart valve
      substitutes. First, a comprehensive review of the state of the art in bioreactors
      is presented and a rigorous classification is put forward. The existing
      bioreactors found in literature are organized in three groups and discussed with
      respect to their quality of reproduction compared to the physiological
      environment. The bioreactor architecture is then decomposed into basic components
      which may be grouped together in different arrangements, and the well-known
      Windkessel approach is used to study the global behavior of the system. Then, the
      new design, which is based on a synthesis of the features of the most evolved
      systems as well as on new improvements, is explained in detail. Optimal fluid
      dynamics are obtained with the presented bioreactor through carefully designed
      components and an advanced computer-controlled actuator. This allows a very
      accurate reproduction of physiological parameters, namely the pulsating flow rate
      and pressure. Finally, experimental results of flow rate and pressure waveforms
      are presented, where an excellent correlation with physiological measurements can
      be observed.

PMID- 19165602
TI  - Apoptosis, autophagy and cell cycle arrest following photodamage to mitochondrial
      interior.
AB  - Cell death induced by oxidative insult targeted to mitochondrial interior of A431
      cells was investigated. For stimulated production of ROS in the inner space of
      mitochondria, safranin-mediated photodynamic treatment (PDT) was employed.
      Another photosensitizer, mTHPC, which diffusely localizes to cellular membranes,
      was used for comparison. Cell response to the oxidative insult in mitochondrial
      interior was different from the response to the photodamage produced in cellular
      membranes. Autophagy and apoptotic features of cell death in response to mTHPC
      PDT was observed in a wide range of PDT doses. Cell response to the oxidative
      stress in mitochondrial interior was dose-dependent. Damage up to CD50 did not
      reveal hallmarks of dead cells. At intermediate damage (CD50), cells manifested
      enhanced autophagy and reduced population of S-phase, but not apoptosis. Severe
      damage (beyond CD70) induced apoptosis following release of cytochrome c and
      caspase activation, in addition to autophagy and cell cycle arrest.

PMID- 19165603
TI  - Design considerations in the development and application of microdisc electrode
      arrays (MDEAs) for implantable biosensors.
AB  - The use of microlithographically fabricated Microdisc Electrode Arrays (MDEAs) in
      the development of implantable voltammetric biosensors necessitates design
      criteria that balances the overall footprint of the device with the advantages to
      be derived from large separation distances between non-interacting microdisc
      elements. Using the dynamic electroanalytical techniques of Multiple Scan Rate
      Cyclic Voltammetry (MSRCV) experiments with finite element simulations and
      Electrochemical Impedance Spectroscopy with equivalent circuit modeling, three
      unique MDEA designs; MDEA 050 (r = 25 microm, 5,184 discs), MDEA 100 (r = 50
      microm, 1,296 discs) and MDEA 250 (r = 125 microm, 207 discs) of constant
      critical dimensions (center-to-center d/r = 4) and area (A = 0.1 cm(2)) were
      studied in 1.0 mM ferrocene monocarboxylic acid (FcCO(2)H) solution (in 0.1 M
      Tris/0.1 M KCl buffer, pH = 7.2). The critical disc-to-disc spacing (d/r)
      required to archive 67% of maximal current response was defined as optimal. Based
      on the predictive model, new MDEA designs; MDEA 001 (r = 0.5 microm, 127,324
      discs), MDEA 002.5 (r = 1.25 microm, 20,372 discs), MDEA 005 (r = 2.5 microm,
      5,093 discs), MDEA 010 (r = 5 microm, 1,273 discs), MDEA 015 (r = 7.5 microm, 566
      discs), MDEA 020 (r = 10 microm, 318 discs) were simulated at 10 and 100 mV/s.
      The final disc count of each MDEA was dictated by the need to maintain a
      comparable electroactive area between the MDEAs, which was chosen to be 0.001
      cm(2), which in turn was dictated by the need to generate sufficient
      electrochemical current to be comfortably measured by common electrochemical
      detectors.

PMID- 19165601
TI  - Cell death pathways in Parkinson's disease: proximal triggers, distal effectors,
      and final steps.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder. Neuronal cell
      death in PD is still poorly understood, despite a wealth of potential pathogenic
      mechanisms and pathways. Defects in several cellular systems have been implicated
      as early triggers that start cells down the road toward neuronal death. These
      include abnormal protein accumulation, particularly of alpha-synuclein; altered
      protein degradation via multiple pathways; mitochondrial dysfunction; oxidative
      stress; neuroinflammation; and dysregulated kinase signaling. As dysfunction in
      these systems mounts, pathways that are more explicitly involved in cell death
      become recruited. These include JNK signaling, p53 activation, cell cycle re
      activation, and signaling through bcl-2 family proteins. Eventually, neurons
      become overwhelmed and degenerate; however, even the mechanism of final cell
      death in PD is still unsettled. In this review, we will discuss cell death
      triggers and effectors that are relevant to PD, highlighting important unresolved
      issues and implications for the development of neuroprotective therapies.

PMID- 19165605
TI  - Survivorship considerations in adults with hereditary breast and ovarian cancer
      syndrome: state of the science.
AB  - INTRODUCTION: Five to 10% of breast cancers are caused by inherited mutations of
      the BRCA1/2 genes. Knowledge of inherited risk for cancer has potential for
      psychosocial consequences. The purpose of this review is to determine the
      survivorship concerns of women with mutations of BRCA1/2; with and without a
      diagnosis of cancer. METHODS: The search strategy included a search of CINAHL,
      PsycINFO, Medline, Pubmed, and Cochrane databases to identify research reports
      with specific aims of determining physical, psychosocial or spiritual outcomes of
      genetic testing for breast and ovarian cancer syndrome in adults at high risk for
      BRCA1/2 mutations. The identified studies were analyzed by design, sampling, and
      outcome measures. They were categorized by domain and main findings by domain are
      summarized. RESULTS: One systematic review, ten qualitative and 27 quantitative
      studies met the inclusion criteria. Four theoretical frameworks were identified.
      DISCUSSION/CONCLUSIONS: Survivorship concerns were multidimensional and included
      issues related to risk reduction procedures, psychological and emotional impacts,
      and impact on family and social relationships. Many adults experience temporary
      distress after receipt of positive BRCA1/2 testing. Usually the distress is not
      clinically significant, however support is desired from health professionals,
      others who have a BRCA1/2 mutation, and family as decisions are made regarding
      screening and risk-reducing options. Social relationships are impacted as
      information is communicated to family members. Limitations of the current state
      of the science, opportunities to build evidence for the future and implications
      for nursing practice and education are identified.

PMID- 19165607
TI  - Enzymatic enrichment of egg-yolk phosphatidylcholine with alpha-linolenic acid.
AB  - alpha-Linolenic acid (ALA) was incorporated at 28% into the sn-1 position of egg
      yolk phospatidylcholine using Novozyme 435 in one-step transesterification
      process. Using phospholipase A(2) in a two-step process gave 25% incorporation of
      ALA into the sn-2 position.

PMID- 19165608
TI  - Assessment of natural arsenic in groundwater in Cordoba Province, Argentina.
AB  - Groundwater in the central part of Argentina contains arsenic concentrations
      that, in most cases, exceed the value suggested by international regulations. In
      this region, Quaternary loessical sediments with a very high volcanic glass
      fraction lixiviate arsenic and fluoride after weathering. The objectives of this
      study are to analyze the spatial distribution of arsenic in different
      hydrogeological regions, to define the naturally expected concentration in an
      aquifer by means of hydrogeochemistry studies, and to identify emergent health
      evidences related to cancer mortality in the study area. The correlation between
      arsenic and fluoride concentrations in groundwater is analyzed at each county in
      the Cordoba Province. Two dimensionless geoindicators are proposed to identify
      risk zones and to rapidly visualize the groundwater quality related to the
      presence of arsenic and fluoride. A surface-mapping system is used to identify
      the spatial variability of concentrations and for suggesting geoindicators. The
      results show that the Chaco-Pampean plain hydrogeologic region is the most
      affected area, with arsenic and fluoride concentrations in groundwater being
      generally higher than the values suggested by the World Health Organization (WHO)
      for drinking water. Mortality related to kidney, lung, liver, and skin cancer in
      this area could be associated to the ingestion of arsenic-contaminated water.
      Generated maps provide a base for the assessment of the risk associated to the
      natural occurrence of arsenic and fluoride in the region.

PMID- 19165609
TI  - Scientific misconduct and participation rates in population-based epidemiological
      research: the NOWAC study.
AB  - To investigate the possible effect of a scientific misconduct case and the
      subsequent immense publicity on the participation rates in a population based
      epidemiological study. We investigated willingness to participate, by donating a
      blood sample, among random samples of 500 women included in the Norwegian women
      and cancer study-NOWAC. The women were asked to participate during a period
      before, under and after the discovery of misconduct January 2006. This population
      based sampling was independent of the case. Letters of invitation and a
      questionnaire were regularly mailed from 2003 till 2006, and here we use the
      period from November till April of two subsequent years; 2004/2005 and 2005/2006.
      Population based in Norway 30,216 Norwegian women born 1943-1957 invited to
      participate. Response rates (%) for returning a blood sample and for actively
      responding with a "No" to the invitation. The active response of a "No" increased
      immediately after the publicity of the scientific misconduct, but lasted only for
      2 months. The response rate for blood samples was only marginally affected in the
      same period, and increased over previous level 3 months after the misconduct was
      publicly known. The widespread publicity related to the scientific misconduct did
      not affect the response rate in this population based study. This might imply
      that the public trust increased as a consequence of the public discussions that
      followed.

PMID- 19165610
TI  - BRMS1 contributes to the negative regulation of uPA gene expression through
      recruitment of HDAC1 to the NF-kappaB binding site of the uPA promoter.
AB  - The BRMS1 metastasis suppressor was recently shown to negatively regulate NF
      kappaB signaling and down regulate NF-kappaB-dependent uPA expression. Here we
      confirm that BRMS1 expression correlates with reduced NF-kappaB DNA binding
      activity in independently derived human melanoma C8161.9 cells stably expressing
      BRMS1. We show that knockdown of BRMS1 expression in these cells using small
      interfering RNA (siRNA) leads to the reactivation of NF-kappaB DNA binding
      activity and re-expression of uPA. Further, we confirm that BRMS1 expression does
      not alter IKKbeta kinase activity suggesting that BRMS1-dependent uPA regulation
      does not occur through inhibition of the classical upstream activators of NF
      kappaB. BRMS1 has been implicated as a corepressor of HDAC1 and consistent with
      this, we show that BRMS1 promotes HDAC1 recruitment to the NF-kappaB binding site
      of the uPA promoter and is associated with reduced H3 acetylation. We also
      confirm that BRMS1 expression stimulates disassociation of p65 from the NF-kappaB
      binding site of the uPA promoter consistent with its reduced DNA binding
      activity. These data suggest that BRMS1 recruits HDAC1 to the NF-kappaB binding
      site of the uPA promoter, modulates histone acetylation of p65 on the uPA
      promoter, leading to reduced NF-kappaB binding activity on its consensus
      sequence, and reduced transactivation of uPA expression.

PMID- 19165611
TI  - Single amino acid sequence polymorphisms in rat cardiac troponin revealed by top
      down tandem mass spectrometry.
AB  - Heterotrimeric cardiac troponin (cTn) is a critical component of the thin
      filament regulatory complex in cardiac muscle. Two of the three subunits, cTnI
      and cTnT, are subject to post-translational modifications such as proteolysis and
      phosphorylation, but linking modification patterns to function remains a major
      challenge. To obtain a global view of the biochemical state of cTn in native
      tissue, we performed high resolution top-down mass spectrometry of cTn
      heterotrimers from healthy adult rat hearts. cTn heterotrimers were affinity
      purified, desalted and then directly subjected to mass spectrometry using a 7
      Tesla Thermo LTQ-FT-ICR instrument equipped with an ESI source. Molecular ions
      for N-terminally processed and acetylated cTnI and cTnT were readily detected as
      were other post-translationally modified forms of these proteins. cTnI was
      phosphorylated with a distribution of un-, mono- and bisphosphorylated forms of
      41 +/- 3%, 46 +/- 1%, 13 +/- 3%, respectively. cTnT was predominantly
      monophosphorylated and partially proteolyzed at the Glu(29)-Pro(30) peptide bond.
      Also observed in high resolution spectra were 'shadow' peaks of similar intensity
      to 'parent' peaks exhibiting masses of cTnI+16 Da and cTnT+128 Da, subsequently
      shown by tandem mass spectrometry (MS/MS) to be single amino acid polymorphisms.
      Intact and protease-digested cTn subunits were fragmented by electron capture
      dissociation or collision activated dissociation to localize an Ala/Ser
      polymorphism at residue 7 of cTnI. Similar analysis of cTnT localized an
      additional Gln within a three residue alternative splice site beginning at
      residue 192. Besides being able to provide unique insights into the global state
      of post-translational modification of cTn subunits, high resolution top-down mass
      spectrometry readily revealed naturally occurring single amino acid sequence
      variants including a genetic polymorphism at residue 7 in cTnI, and an
      alternative splice isoform that affects a putative hinge region around residue
      192 of cTnT, all of which co-exist within a single rat heart.

PMID- 19165612
TI  - Assessment of heavy metal contamination in the sediments of Nansihu Lake
      Catchment, China.
AB  - At present, anthropogenic contribution of heavy metals far exceeds natural input
      in some aquatic sediment, but the proportions are difficult to differentiate due
      to the changes in sediment characters. In this paper, the metal (Al, Fe, K, Mg,
      Ca, Cr, Cu, Ni, and Zn) concentrations, grain size, and total organic carbon
      (TOC) content in the surface and core sediments of Nansihu Lake Catchment (the
      open lake and six inflow rivers) were determined. The chemical speciations of the
      metals (Al, Fe, Cr, Cu, Ni, and Zn) in the surface sediments were also analyzed.
      Approaches of factor analysis, normalized enrichment factor (EF) and the new non
      residual fractions enrichment factor (K(NRF)) were used to differentiate the
      sources of the metals in the sediments, from detrital clastic debris or
      anthropogenic input, and to quantify the anthropogenic contamination. The results
      indicate that natural processes were more dominant in concentrating the metals in
      the surface and core sediments of the open lake. High concentration of Ca and
      deficiency of other metals in the upper layers of the sediment core were
      attributed to the input of carbonate minerals in the catchment with increasing
      human activities since 1980s. High TOC content magnified the deficiency of the
      metals. Nevertheless, the EF and K(NRF) both reveal moderate to significant
      anthropogenic contamination of Cr, Cu, Ni, and Zn in the surface sediments of
      Laoyun River and the estuary and Cr in the surface sediments of Baima River. The
      proportion of non-residual fractions (acid soluble, reducible, and oxidizable
      fractions) of Cr, Cu, Ni, and Zn in the contaminated sediments increased to 37
      99% from the background levels less than 30%.

PMID- 19165613
TI  - Bacteria holding times for fecal coliform by mFC agar method and total coliform
      and Escherichia coli by Colilert-18 Quanti-Tray method.
AB  - Bacteria holding-time experiments of up to 62 h were performed on five surface
      water samples from four urban stream sites in the vicinity of Atlanta, GA, USA
      that had relatively high densities of coliform bacteria (Escherichia coli
      densities were all well above the US Environmental Protection Agency criterion of
      126 colonies (100 ml)(-1) for recreational waters). Holding-time experiments were
      done for fecal coliform using the membrane filtration modified fecal coliform
      (mFC) agar method and for total coliform and E. coli using the Colilert-18 Quanti
      Tray method. The precisions of these analytical methods were quantified.
      Precisions determined for fecal coliform indicated that the upper bound of the
      ideal range of counts could reasonably be extended upward and would improve
      precision. For the Colilert-18 method, analytical precisions were similar to the
      theoretical precisions for this method. Fecal and total coliform densities did
      not change significantly with holding times up to about 27 h. Limited information
      indicated that fecal coliform densities might be stable for holding times of up
      to 62 h, whereas total coliform densities might not be stable for holding times
      greater than about 27 h. E. coli densities were stable for holding times of up to
      18 h--a shorter period than indicated from a previous studies. These results
      should be applicable to non-regulatory monitoring sampling designs for similar
      urban surface-water sample types.

PMID- 19165614
TI  - Quantifying structural physical habitat attributes using LIDAR and hyperspectral
      imagery.
AB  - Structural physical habitat attributes include indices of stream size, channel
      gradient, substrate size, habitat complexity, and riparian vegetation cover and
      structure. The Environmental Monitoring and Assessment Program (EMAP) is designed
      to assess the status and trends of ecological resources at different scales. High
      resolution remote sensing provides unique capabilities in detecting a variety of
      features and indicators of environmental health and condition. LIDAR is an
      airborne scanning laser system that provides data on topography, channel
      dimensions (width, depth), slope, channel complexity (residual pools, volume,
      morphometric complexity, hydraulic roughness), riparian vegetation (height and
      density), dimensions of riparian zone, anthropogenic alterations and
      disturbances, and channel and riparian interaction. Hyperspectral aerial imagery
      offers the advantage of high spectral and spatial resolution allowing for the
      detection and identification of riparian vegetation and natural and anthropogenic
      features at a resolution not possible with satellite imagery. When combined, or
      fused, these technologies comprise a powerful geospatial data set for assessing
      and monitoring lentic and lotic environmental characteristics and condition.

PMID- 19165616
TI  - Factors affecting urethral stricture development after radical retropubic
      prostatectomy.
AB  - OBJECTIVE: We determined the factors that can cause urethral stricture after
      radical retropubic prostatectomy. MATERIALS AND METHODS: A total of 56 patients
      underwent radical retropubic prostatectomy for clinically localized prostate
      cancer between June 2004 and July 2006. The patients were invited for cystography
      and removal of the urethral catheter at the 7th postoperative day if no
      extravasation was seen. Otherwise, the same procedures were repeated at
      postoperative days 14 and 21 until complete healing at urethrovesical anastomosis
      was observed. The patients were followed up for the occurrence of urethral
      stricture with PSA blood levels, residual urine assessment and uroflowmetry at
      least for 1 year. The impact of age, preoperative PSA level, prostate weight,
      biopsy Gleason score, bladder neck reconstruction, neurovascular bundle
      preservation, presence of a water-tight anastomosis, amount of peroperative
      bleeding and catheter removal time on the development of urethral stricture was
      evaluated with logistic regression analysis. RESULTS: A statistically significant
      correlation was observed between catheter removal time, which reflects complete
      healing of the urethrovesical anastomosis, and development of urethral stricture
      (P = 0.004). Only 1 (4%) of 25 patients whose catheter was removed on
      postoperative day 7 developed urethral stricture, whereas 2 of 16 (12.5%) and 6
      of 15 (40%) patients whose catheters were removed on postoperative days 14 and 21
      developed urethral strictures. Additionally, patients with postoperative urethral
      strictures were found to be slightly older than those without (67.4 +/- 4.5 vs.
      63.1 +/- 6.5, P = 0.048). CONCLUSION: Our study showed that early healing of
      vesico-urethral anastomosis may allow early catheter removal and results in
      decreased rates of urethral stricture formation.

PMID- 19165615
TI  - Induction of focal epithelial hyperplasia in tongue of young bk6-E6/E7 HPV16
      transgenic mice.
AB  - Squamous cell carcinoma (SCC) of the oral cavity is one of the most common
      neoplasms in the world. During the past 2 decades, the role of high-risk human
      papilloma virus (HR-HPV) has been studied and the data supporting HPV as a one of
      the causative agents in the development and progression of a sub-set of head and
      neck squamous cell carcinomas (HNSCC) has accumulated. In order to investigate
      the role of HR-HPV oncogene expression in early epithelial alterations in vivo,
      we produced transgenic mice expressing HPV16 early region genes from the promoter
      of the bovine keratin 6 gene (Tg[bK6-E6/E7]). In this article, we demonstrate
      that E6/E7 transgene was abundantly expressed and cellular proliferation was
      increased in the middle tongue epithelia of transgenic mice, and that in the same
      region young (27 weeks old) Tg[bK6-E6/E7] mice spontaneously developed
      histological alterations, mainly focal epithelial hyperplasia (FEH).

PMID- 19165617
TI  - Effectiveness of totally tubeless percutaneous nephrolithotomy in selected
      patients: a prospective randomized study.
AB  - OBJECTIVES: Compared with the standard technique, the number of percutaneous
      nephrolithotomy (PCNL) operations without a drainage catheter is increasing in
      recent years. In this prospective randomized study, we compared the morbidity of
      totally tubeless (tubeless and stentless) PCNL operations with the standard
      operation technique in a single center with a selected patient population.
      METHODS: Ninety patients who fulfilled the criteria were included. Forty-five
      patients underwent totally tubeless PCNL (Group 1) and a 14F malecot nephrostomy
      catheter was used in another set of 45 patients (Group 2). Inclusion criteria for
      the study were no serious bleeding or perforation in the collecting system during
      the operation, stone free or clinically insignificant residual fragments (CIRF <4
      mm), and no more than one access. RESULTS: When two groups were compared with
      regard to age, stone volume, postoperative hemoglobin change, transfusion rate,
      and operation time, no significant differences were found between the two groups.
      However, a significant difference was found in hospitalization time between the
      two groups (P < 0.05). The amount of non-steroidal analgesic (tenoxicam) needed
      and non-steroidal analgesia-resistant pain which was resolved with narcotic
      analgesics (meperidine) were significantly lower in Group 1 (P < 0.05).
      Complications were observed in two patients (4.5%) in Group 1 (one
      retroperitoneal hematoma, one long-lasting renal colic) and in six patients
      (13.3%) in Group 2 (five prolonged urine drainage, one long-lasting fever) (P <
      0.05). CONCLUSIONS: Tubeless and stentless PCNL is a safe method and reduces
      hospitalization time and analgesic requirement, and promotes quality of life in
      selected patients.

PMID- 19165618
TI  - Congenital disorder of glycosylation type Ia in a Malaysian family: clinical
      outcome and description of a novel PMM2 mutation.
AB  - There are few reports of congenital disorders of glycosylation (CDGs) in the
      Asian population, although they have been reported worldwide. We identified a
      Malaysian infant female at 2 days of life with CDG type Ia. The diagnosis was
      suspected on the basis of inverted nipples and abnormal fat distribution. She had
      cerebellar hypoplasia and developed coagulopathy, hypothyroidism and severe
      pericardial effusion and died at 7 months of life. The diagnosis was supported by
      abnormal serum transferrin isoform pattern that showed elevated levels of the
      disialotransferrin isoform and trace levels of the asialotransferrin isoform.
      Enzyme testing of peripheral leukocytes showed decreased level of
      phosphomannomutase (PMM) activity (0.6 nmol/min per mg protein, normal range 1.6
      6.2) and a normal level of phosphomannose isomerase activity (19 nmol/min per mg
      protein, normal range 12-25), indicating a diagnosis of CDG type Ia. Mutation
      study of the PMM2 gene showed the patient was heterozygous for both the common
      p.R141H (c.422T>A) mutation and a novel sequence change in exon 7, c.618C>A. The
      latter change is predicted to result in the replacement of the highly conserved
      phenylalanine residue at position 206 with a leucine residue (p.F206L) and occurs
      in the same codon as the previously reported p.F206S mutation. Analysis of 100
      control chromosomes has shown that the p.F206L sequence change is not present,
      making it highly likely that this change is functionally important. To the best
      of our knowledge, this is the first report of CDG in the Malay population.
      Prenatal diagnosis was successfully performed in a subsequent pregnancy for this
      family.

PMID- 19165621
TI  - CT coronary angiography of chronic total occlusions of the coronary arteries: how
      to recognize and evaluate and usefulness for planning percutaneous coronary
      interventions.
AB  - Chronic total occlusions (CTO) of the coronary arteries are a common finding. A
      CTO can be underdiagnosed on CT coronary angiography (CTCA) as a high grade
      stenosis, because of the presence of retrograde collaterals which allow
      opacification of the vessel distal to the stenosis, or can be missed completely,
      especially if another adjacent opacified artery is mistaken for occluded artery.
      CTOs are considered as Type C or high risk lesions with a higher restenosis rate
      and increased technical failure rate by percutaneous coronary intervention (PCI).
      CTCA can help identify features that most influence current success rates of PCI
      such as marked calcifications at the stump, severe tortuosity of the proximal
      vessel, long length of the occluded segment as well location of the vessel distal
      to the occlusion, which often may not be well seen on conventional angiography.
      Identification of these features and displaying the 3D information as the best
      angiographic projection that demonstrates the length and orientation of the CTO,
      either as hard copy images or transmitted direct to the angiographic catheter lab
      for data fusion, allows strategic preprocedural planning and scheduling of the
      PCI. Myocardial viability of the affected area of the occluded segment is a major
      factor that influences whether PCI for CTO is attempted but is not currently
      readily available by cardiac CT. Contrast enhanced cardiac MR imaging is still
      the gold standard for this and may need to be performed prior to PCI.

PMID- 19165622
TI  - Frequency and distribution of late gadolinium enhancement in magnetic resonance
      imaging of patients with apical hypertrophic cardiomyopathy and patients with
      asymmetrical hypertrophic cardiomyopathy: a comparative study.
AB  - Our aim was to compare the frequency and distribution of late gadolinium
      enhancement (LGE) on contrast MRI between hypertrophic cardiomyopathy (HCM)
      patients with apical hypertrophic cardiomyopathy (APH) and those with
      asymmetrical septal hypertrophy (ASH). We studied 66 patients with HCM (50 men
      and 16 women; average age: 58.8 +/- 29.8 years) who had undergone MRI. All the
      MRI examinations were performed using a 1.5 T system. LGE images were acquired
      using the inversion recovery segmented spoiled-gradient echo and phase-sensitive
      inversion recovery methods. We evaluated 17 segments of the left ventricle as
      defined by the American Heart Association criteria for LGE determination. LGE was
      detected at the junction of the right ventricle and the interventricular septum
      in 25 (73.5%) of the 34 HCM patients with ASH and in the apex of the heart in 13
      (40.6%) of the 32 patients with APH. LGE-positive areas were more widely
      distributed in the case of the ASH group than in the case of the APH group. The
      distribution of LGE was clearly different between the two groups (Fisher's exact
      probability test, P = 0.0068). The number of LGE-positive cases and LGE-positive
      segments were significantly higher in the ASH group than in the APH group and
      there was a significant difference in the distribution of the LGE-positive areas
      between the two groups. LGE was mainly detected in the hypertrophied areas of the
      myocardium.

PMID- 19165623
TI  - Silencing of PMT expression caused a surge of anatabine accumulation in tobacco.
AB  - Drastic increase of anatabine levels was observed in tobacco plants with markedly
      reduced nicotine concentrations through RNA silencing approaches. By down
      regulation of PMT through three kinds of RNA silencing approaches, the nicotine
      levels decreased accordingly. In lines with slight and moderate reduction of
      nicotine levels, no anticipated negative linear correlation was found between
      anatabine and nicotine content. In lines with nicotine levels lower than 2.7
      mg/g, drastic elevation of anatabine levels was found. Transcriptional levels of
      QPRT were unaffected in tobacco lines with surged anatabine levels. This report
      of an intriguing mutual relationship of nicotine and anatabine sheds new light on
      mechanisms between metabolic regulations in plants, and reconfirms complexity of
      metabolic networks.

PMID- 19165624
TI  - Validation of modified forms of the PedsQL generic core scales and cancer module
      scales for adolescents and young adults (AYA) with cancer or a blood disorder.
AB  - PURPOSE: To validate two health-related quality of life (HRQOL) measures, the
      PedsQL Generic Core and Cancer Module adolescent forms (13-18 years), after
      modification for 16-25-year-old adolescents and young adults (AYA) with cancer or
      a blood disorder. METHODS: AYA patients and nominated proxies were recruited from
      three Sydney hospitals. Modified forms were administered by telephone or in
      clinics/wards. Analyses included correlations, factor analysis, and analysis of
      variance of known-groups (defined by the Memorial Symptom Assessment Scale).
      RESULTS: Eighty-eight patients and 79 proxies completed questionnaires. Factor
      structures consistent with those of the unmodified forms confirmed construct
      validity. Cronbach's alpha ranged 0.81-0.98. Inter-scale correlations were as
      hypothesized, confirming discriminant validity. Statistically significant
      differences between groups with mild, moderate, and severe symptoms (P < 0.05)
      confirmed clinical validity. CONCLUSION: These modified forms provide reliable
      and valid measures of HRQOL in AYA with cancer or a blood disorder, suitable for
      clinical trials, research, and practice.

PMID- 19165625
TI  - Lymphocyte recruitment into the tumor site is altered in patients with MSI-H
      colon cancer.
AB  - The ability of the host to mount an appropriate immune response to aberrant cells
      is one factor that determines prognosis in cancer patients. Naturally occurring
      regulatory T cells (T regs; CD4+ CD25+ cells) are key regulators of peripheral
      tolerance. It has been suggested that high levels of T regs are detrimental to
      the patient in some forms of cancer, but the role of these antigen-specific cells
      in individuals with colorectal cancers with high levels of microsatellite
      instability is unknown. Herein, we examined the ability of individuals with MSI-H
      or microsatellite stable colon cancer to recruit lymphocytes to the tumor site.
      Immunohistochemical staining was performed on archived paraffin-embedded
      specimens from a total of 38 individuals with MSI-H (n = 25) or MSS (n = 13)
      colon cancers to determine the proportion of CD3+, CD8+ and CD25+ cells
      infiltrating the tumor site. Patients with MSI-H colon cancers had increased
      percentages of CD8+ TILs (cytotoxic T cells) as compared to individuals with MSS
      colon cancer (47.3 vs. 24.04% of the infiltrate CD8+, respectively). No
      differences in the levels of CD25+ T cells were observed between individuals with
      MSI-H colon cancers and MSS colon cancers (0.53 vs. 0.54% CD25+, respectively).
      Together, these data suggest that the survival advantage enjoyed by patients with
      MSI-H colorectal cancer may, in part, be attributed to the increased cytolytic
      response, but not to an antigen-specific immunosuppressive response in MSS
      patients.

PMID- 19165627
TI  - Hexavalent chromium reduction by free and immobilized cell-free extract of
      Arthrobacter rhombi-RE.
AB  - In the present study, hexavalent chromium (Cr(VI)) reduction potential of
      chromium reductase associated with the cell-free extracts (CFE) of Arthrobacter
      rhombi-RE species was evaluated. Arthrobacter rhombi-RE, an efficient Cr(VI)
      reducing bacterium, was enriched and isolated from a chromium-contaminated site.
      Chromium reductase activity of Arthrobacter rhombi-RE strain was associated with
      the cell-free extract and the contribution of extracellular enzymes to Cr(VI)
      reduction was negligible. NADH enhanced the chromium reductase activity. The
      enzyme activity was optimal at a pH of 5.5 and a temperature of 30 degrees C.
      Among the ten electron donors screened, sodium pyruvate was the most effective
      one followed by NADH and propionic acid. Michaelis-Menten constant, K(m), and
      maximum reaction rate, V(max), obtained from the Lineweaver-Burk plot were 48
      microM and 4.09 nM/mg protein/min, respectively, in presence of NADH as electron
      donor and 170.5 microM and 4.29 nM/mg protein/min, respectively, in presence of
      sodium pyruvate as electron donor. Ca(2+) enhanced the enzyme activity while
      Hg(2+), Cd(2+), Ba(2+), and Zn(2+) inhibited the enzyme activity. Among the
      various immobilization matrices screened, calcium alginate beads seemed to be the
      most effective one. Though immobilized enzyme system was able to reduce Cr(VI),
      the performance was not very encouraging in continuous mode of operation.

PMID- 19165626
TI  - Men in the women's world of hereditary breast and ovarian cancer--a systematic
      review.
AB  - Little is known about men seeking genetic counseling for hereditary breast and
      ovarian cancer (HBOC). We review the sparse literature on men attending such
      genetic consultations. Two main themes are identified: the women's influence on
      the genetic counseling process, and the psychological impact on men. The women in
      the HBOC families have an influence on the men's decision to request genetic
      testing, and they take the leading role in communicating genetic information.
      With respect to psychological impact, the men suffer from grief and fear of
      developing cancer, and they seem to use avoidance as a coping strategy. Carrier
      males experience feelings of guilt because they might have passed on a mutation
      to their children. Non-carriers experience test-related stress if their siblings
      tested positive. Mutation status may have an impact on reproductive issues. These
      findings are discussed in light of gender issues and literature concerning men's
      health behavior. Further studies are needed to provide optimal care for men
      seeking genetic counseling for hereditary breast and ovarian cancer.

PMID- 19165628
TI  - Effect and modeling of glucose inhibition and in situ glucose removal during
      enzymatic hydrolysis of pretreated wheat straw.
AB  - The enzymatic hydrolysis of lignocellulosic biomass is known to be product
      inhibited by glucose. In this study, the effects on cellulolytic glucose yields
      of glucose inhibition and in situ glucose removal were examined and modeled
      during extended treatment of heat-pretreated wheat straw with the cellulolytic
      enzyme system, Celluclast 1.5 L, from Trichoderma reesei, supplemented with a
      beta-glucosidase, Novozym 188, from Aspergillus niger. Addition of glucose (0-40
      g/L) significantly decreased the enzyme-catalyzed glucose formation rates and
      final glucose yields, in a dose-dependent manner, during 96 h of reaction. When
      glucose was removed by dialysis during the enzymatic hydrolysis, the cellulose
      conversion rates and glucose yields increased. In fact, with dialytic in situ
      glucose removal, the rate of enzyme-catalyzed glucose release during 48-72 h of
      reaction recovered from 20-40% to become approximately 70% of the rate recorded
      during 6-24 h of reaction. Although Michaelis-Menten kinetics do not suffice to
      model the kinetics of the complex multi-enzymatic degradation of cellulose, the
      data for the glucose inhibition were surprisingly well described by simple
      Michaelis-Menten inhibition models without great significance of the inhibition
      mechanism. Moreover, the experimental in situ removal of glucose could be
      simulated by a Michaelis-Menten inhibition model. The data provide an important
      base for design of novel reactors and operating regimes which include continuous
      product removal during enzymatic hydrolysis of lignocellulose.

PMID- 19165629
TI  - Enhanced pervaporation performance of multi-layer PDMS/PVDF composite membrane
      for ethanol recovery from aqueous solution.
AB  - Multi-layer PDMS/PVDF composite membrane with an alternative PDMS/PVDF/non-woven
      fiber/PVDF/PDMS configuration was prepared in this paper. The porous PVDF
      substrate was obtained by casting PVDF solution on both sides of non-woven fiber
      with immersion precipitation phase inversion method. Polydimethylsiloxane (PDMS)
      was then cured by phenyltrimethoxylsilane (PTMOS) and coated onto the surface of
      porous PVDF substrate one layer by the other to obtain multi-layer PDMS/PVDF
      composite membrane. The multi-layer composite membrane was used for ethanol
      recovery from aqueous solution by pervaporation, and exhibited enhanced
      separation performance compared with one side PDMS/PVDF composite membranes,
      especially in the low ethanol concentration range. The maximum separation factor
      of multi-layer PDMS/PVDF composite membrane was obtained at 60 degrees C, and the
      total flux increased exponentially along with the increase of temperature. The
      composite membrane gave the best pervaporation performance with a separation
      factor of 15, permeation rate of 450 g/m(2)h with a 5 wt.% ethanol concentration
      at 60 degrees C.

PMID- 19165630
TI  - Effect of ceramide on mesenchymal stem cell differentiation toward adipocytes.
AB  - Proinflammatory cytokines such as tumor necrosis factor (TNF) alpha are well
      known to inhibit adipocyte differentiation. TNF-alpha triggers ceramide synthesis
      through binding of TNF-alpha to its p55 receptor. Therefore, ceramide is
      implicated in many of the multiple signaling pathways initiated by TNF-alpha. In
      breast tissue engineering, it is important to know how to modulate adipocyte
      differentiation of the stem cells with exogenous additives like ceramide in
      vitro. We hypothesized that stem cell adipogenesis could be retained in TNF-alpha
      treated preadipocytes in which ceramide synthesis was blocked and that exogenous
      ceramide could inhibit adipocyte differentiation. We first studied the effect of
      ceramide synthase inhibitor, Fumonisin B2, on the adipogenesis of murine
      mesenchymal stem cells (D1 cells), treated with TNF-alpha. We then studied the
      effect of specific exogenous C6-ceramide on D1 cell viability and
      differentiation. It was found that 1 ng/ml of TNF-alpha significantly inhibited
      D1 cell adipogenesis. Cells treated with 5 microM of Fumonisin B2 were able to
      undergo adipogenesis, even when treated with TNF-alpha. High concentrations of
      exogenous C6-ceramide (>50 microM) had an inhibitory effect, not only on the pre
      confluent proliferation of the D1 cells but also on the post-confluent cell
      viability. High concentrations of C6-ceramide (>50 microM) also inhibited mitotic
      clonal expansion when D1 cell differentiation was induced by the addition of an
      adipogenic hormonal cocktail. C6-ceramide at low concentrations (10-25 microM)
      inhibited lipid production in D1 cells, demonstrated by decreased levels of both
      total triglyceride content and specific fatty acid composition percentages.
      Genetic expression of peroxisome proliferator-activated receptor (PPAR) gamma and
      aP2 in D1 cells was reduced by C6-ceramide treatment. CCAAT/enhancer-binding
      protein (C/EBP) beta levels in D1 cells were reduced by C6-ceramide treatment
      during early differentiation; PPARgamma and aP2 protein levels were reduced at
      terminal differentiation. C6-ceramide at lower concentrations also decreased
      lipid accumulation of differentiating D1 cells. Our results suggest that ceramide
      synthase inhibitor retains the adipogenic potential of TNF-alpha-treated
      mesenchymal stem cells, while exogenous ceramide at lower concentrations inhibit
      the adipogenesis of mesenchymal stem cells. Ceramide, therefore, could be a
      modulator candidate in breast tissue engineering strategies.

PMID- 19165631
TI  - Process modeling of comprehensive integrated forest biorefinery--an integrated
      approach.
AB  - The key to expanding the energy supply, increasing energy security, and reducing
      the dependency on foreign oil is to develop advanced technologies to efficiently
      transform our renewable bioresources into domestically produced bioenergy and
      bioproducts. Conventional biorefineries, i.e., forest products industry's pulp
      and paper mills with long history of sustainable utilization of lignocellulose
      (wood), offer a suitable platform for being expanded into future integrated
      forest biorefineries. Due to the pre-existing infrastructure in current forest
      products operations, this could present a very cost-effective approach to future
      biorefineries. In order to better understand the overall process, technical,
      economic, and environmental impacts, a detailed process modeling of the whole
      integrated forest biorefinery is presented here. This approach uses a combination
      of Aspen Plus, WinGEMS, and Microsoft Excel to simulate the entire biorefinery in
      detail with sophisticated communication interface between the three simulations.
      Preliminary results for a simple case study of an integrated biorefinery show the
      feasibility of this approach. Further investigations, including additional
      details, more process options, and complete integration, are currently underway.

PMID- 19165632
TI  - Correspondence between neurological deficit, cerebral infarct size, and Rho
      kinase activity in a rat cerebral thrombosis model.
AB  - Whether Rho-kinase activity is really associated with the pathogenesis of
      cerebral infarction remains unclear. To consider this question, we investigated
      correspondences between severity of neurological deficit, infarct size, amount of
      various marker proteins, and Rho-kinase activity in a rat cerebral infarction
      model. Sodium laurate was injected into the left internal carotid artery,
      inducing cerebral infarction in the ipsilateral hemisphere in rats. We prepared
      rats with various severities of neurological deficit (mild to severe) 3 days
      after injection of laurate, then measured infarct size and amount of various
      marker proteins, phosphorylation of substrates of Rho-kinase, myosin-binding
      subunit (MBS), myosin light chain (MLC), ezrin/radixin/moesin (ERM), and adducin
      using Western blot methods. First, infarct size increased corresponding to the
      severity of neurological deficit. Second, amounts of activating transcription
      factor 3, nestin, CD68, proliferating cell nuclear antigen, and heat shock
      protein 70 were increased, whereas neurofilament and myelin-associated
      glycoprotein were decreased corresponding to the severity of neurological deficit
      and infarct size. Finally, Rho-kinase activity (phospho-MBS/MBS, phospho-MLC/MLC,
      phospho-ERM/ERM, and phospho-adducin/adducin) was increased corresponding to the
      severity of neurological deficit and infarct size. Rho-kinase thus appears to
      play a crucial role in the pathogenesis of cerebral infarction.

PMID- 19165633
TI  - Neuroprotective protein and carboxypeptidase E.
AB  - This review outlines the neuroprotective activities and structural specificities
      of two distinct proteins, activity-dependent neuroprotective protein, a protein
      assigned transcription factor/chromatin remodeling activity, and carboxypeptidase
      E, a classic exopeptidase. Future studies will elucidate how these two versatile
      proteins converge onto a similar endpoint: neuroprotection.

PMID- 19165634
TI  - Patterns of increased intracranial pressure after severe traumatic brain injury.
AB  - INTRODUCTION: Secondary brain injury due to increased intracranial pressure (ICP)
      contributes to post-traumatic morbidity and mortality. Although it is often
      taught that increased ICP begins early after traumatic brain injury, some
      patients develop increased ICP after the first 3 days post-injury. We examined
      our data to describe temporal patterns of increased ICP. METHODS: This is a
      retrospective review of prospectively collected physiologic and demographic data.
      RESULTS: Seventy-seven patients were included. We identified four patterns of
      increased ICP: beginning within 72 h (early), beginning after 72 h (late), early
      increases with resolution, and then a second rise after 72 h (bimodal), and
      continuously increased ICP. Late increases in ICP occur in 17% of this cohort.
      Peak day of swelling was day 7 for the "late" rise group and day 4 for the other
      patients with increased ICP. Forty-four percent of patients showed enlargement of
      cerebral contusions on follow-up imaging at 24 h post-injury. CONCLUSIONS: Late
      rises in ICP were not rare in this cohort. This is clinically relevant as it may
      impact decisions about ICP monitor removal. Differences between groups in age, CT
      patterns of injury, fluid therapy, osmotic use, and fever were not statistically
      significant.

PMID- 19165635
TI  - A cellular viewpoint of anti-FVIII immune response in hemophilia A.
AB  - A large proportion of hemophilia A patients who receive replacement therapy,
      develop an immune response toward the infused factor VIII (FVIII). In this
      review, we discuss recent progress in several aspects of the anti-FVIII immune
      response, focusing on the sites of FVIII endocytosis (marginal zone of the spleen
      and bleeding site), the type of antigen-presenting cells (dendritic cells,
      macrophages and B cells) and endocytic receptors, implicated in FVIII
      presentation to T cells during primary and secondary immune response. Although it
      is becoming increasingly clear that regulatory T cells are involved in FVIII
      tolerance in healthy subjects and potentially in patients without inhibitors, we
      would like to demonstrate that little is known about the different T cells
      subsets and the cytokines network, which are also crucial for the development of
      allo- and autoimmune diseases. As more information on these issues becomes
      available, a better understanding of the role of each immune cells compartment in
      promoting FVIII tolerance or inhibitors development might lead to new strategies
      to promote FVIII tolerance in hemophilia A patients.

PMID- 19165636
TI  - Fructose-rich diet-induced abdominal adipose tissue endocrine dysfunction in
      normal male rats.
AB  - We have currently studied the changes induced by administration of a fructose
      rich diet (FRD) to normal rats in the mass and the endocrine function of
      abdominal (omental) adipose tissue (AAT). Rats were fed ad libitum a standard
      commercial chow and tap water, either alone (control diet, CD) or containing
      fructose (10%, w/vol) (FRD). Three weeks after treatment, circulating metabolic
      markers and leptin release from adipocytes of AAT were measured. Plasma free
      fatty acids (FFAs), leptin, adiponectin, and plasminogen activator inhibitor-1
      (PAI-1) levels were significantly higher in FRD than in CD rats. AAT mass was
      greater in FRD than in CD rats and their adipocytes were larger, they secreted
      more leptin and showed impaired insulin sensitivity. While leptin mRNA expression
      increased in AAT from FRD rats, gene expression of insulin receptor substrate,
      IRS1 and IRS2 was significantly reduced. Our study demonstrates that
      administration of a FRD significantly affects insulin sensitivity and several AAT
      endocrine/metabolic functions. These alterations could be part of a network of
      interacting abnormalities triggered by FRD-induced oxidative stress at the AAT
      level. In view of the impaired glucose tolerance observed in FRD rats, these
      alterations could play a key role in both the development of metabolic syndrome
      (MS) and beta-cell failure.

PMID- 19165637
TI  - Recurrent solitary fibrous tumor of the pleura: significant response to
      radiotherapy.
AB  - Solitary fibrous tumor (SFT) of the pleura is an uncommon neoplasm with non
      specific symptoms and non-pathognomonical radiological findings. Surgery allows
      establishment of a definitive diagnosis as well as a cure of the disease. The
      role of radiotherapy or chemotherapy in the management of the disease is unclear
      because of the rarity of the disease and the successful results of the surgical
      treatment. Long-term clinical follow-up may be useful for the patients with SFT
      because of the potential adverse biological behavior of this tumor, which may
      lead to repeated recurrences and/or malignant transformation. We reported a 66
      year-old woman with recurrence of SFT in the right lung, which had significant
      response to external thoracic radiotherapy.

PMID- 19165638
TI  - Treatment selection for patients with metastatic renal cell carcinoma:
      identification of features favoring upfront IL-2-based immunotherapy.
AB  - The availability of approved agents with distinct mechanisms of action
      (immunotherapy, vascular endothelial growth factor pathway, and mTOR inhibitors)
      has complicated treatment decisions for patients with advanced kidney cancer.
      High-dose IL-2 therapy is the only treatment that can produce durable complete
      responses; however, it has significant side effects and the vast majority of
      patients do not benefit. Thus, identifying the optimal patients to receive first
      line IL-2 therapy is a priority. Past studies have identified some clinical
      features that might be associated with benefit from IL-2-based immunotherapy.
      Subsequent investigations of tumors from patients treated with IL-2 suggested
      that response was unlikely in patients with tumors with papillary features or low
      carbonic anhydrase IX (CAIX) expression. A model combining histologic features
      and CAIX expression separated patients into two groups of roughly equal size,
      with 96% of long-term responding patients being in the favorable prognostic
      group. This model is currently undergoing prospective validation. More recent
      studies involving gene expression profiling and array CGH have begun to identify
      additional features that might predict response to IL-2 therapy. Taken together,
      these data offer the possibility to limit the use of this toxic therapy to those
      most likely to benefit.

PMID- 19165639
TI  - Physical training decreases waist circumference in postmenopausal borderline
      overweight women.
AB  - OBJECTIVE: To examine if healthy borderline overweight postmenopausal women with
      osteoporosis can improve their waist circumference and lipid profile with a
      moderate physical training program. DESIGN: Randomized controlled trial. SETTING:
      One hundred and twelve postmenopausal women were randomized to normal sedentary
      life or one year of physical training consisting of three brisk walks and 1-2
      aerobic exercises/week. MAIN OUTCOME MEASURES: Waist circumference reduction,
      waist circumference reduction in relation to observed level of participation in
      physical intervention and changes in cholesterol, triglycerides, apolipoproteins
      B and A1 and high-sensitivity C-reactive protein (hs-CRP). RESULTS: At start the
      mean (SD) waist circumference was 83.6 (7.7) and 81.8 (7.5) cm in the control and
      training groups, respectively. In relation to baseline, the 12 months
      intervention led to a waist reduction of 0.3 cm (2.7) (p=0.36) and 1.6 cm (4.7)
      (p=0.02) in the respective groups but the inter-group comparison was not
      significant in an intention-to-treat analysis (p=0.09). The ninety-two women
      completing the study intervention were analyzed per protocol. A tendency for
      better waist reduction in relation to the women's observed physical intensity
      level was observed (p=0.07, ANOVA for linear trend across training intensity
      levels). Training women improved their waist circumference 1.7 cm (p=0.01)
      compared to baseline and was borderline significantly better than controls
      (p=0.059). No significant changes in response to the intervention were observed
      for blood pressure, cholesterol, triglycerides, apolipoproteins and hs-CRP.
      CONCLUSIONS: A moderate physical exercise program for healthy postmenopausal
      women during one year reduced the waist circumference in a training intensity
      dependent manner.

PMID- 19165640
TI  - Adult T-cell leukemia/lymphoma (ATL) presenting in the skin: clinical,
      histological and immunohistochemical features of 52 cases.
AB  - BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is a severe disease caused by
      HTLV-I. This paper describes the clinicopathological and immunohistochemical
      findings of 52 cases of ATL with skin involvement and investigates whether there
      is any relationship between median survival time (MST) and histological patterns,
      primary cutaneous involvement and CD8 positivity. MATERIAL AND METHODS: All cases
      were HTLV-I+ and HIV- and were clinically classified. HTLV-I proviral integration
      was investigated in atypical cases. Immunohistochemistry was performed using CD3,
      CD4, CD5, CD7, CD8, CD20, CD25, CD30 and CD45RO markers. Ki-67 was used to
      evaluate the proliferative index. RESULTS: Twenty-seven cases were primary, while
      25 were secondary. Monoclonal viral integration was demonstrated in all atypical
      cases. Patterns resembling mycosis fungoides (MF) were found in 19 cases and
      anaplastic large-cell lymphoma (ALCL) in two cases. Fifteen cases had an atypical
      immunophenotype and expressed CD8. Primary cutaneous ATL had a longer MST (48
      months) than the secondary cutaneous ATL (7 months) and the difference was
      statistically significant, but no statistically significant difference was found
      between the MST of CD8-positive and negative cases. CONCLUSIONS: It is important
      to differentiate between primary and secondary cutaneous ATL and classify the
      cases histologically in order to better evaluate the prognosis. The two forms of
      primary cutaneous ATL, primary cutaneous smoldering and primary cutaneous tumoral
      (PCT), should also be identified. The smoldering type presented a longer survival
      (58 months) and histological aspects suggestive of better prognosis in contrast
      to the PCT type that had a shorter survival (20 months) and histological
      characteristics suggestive of worse outcome.

PMID- 19165641
TI  - In response to 'Behind EUD'.

PMID- 19165642
TI  - Fatal drug-drug interaction of brivudine and capecitabine.

PMID- 19165643
TI  - Substantial variation in the cardiac differentiation of human embryonic stem cell
      lines derived and propagated under the same conditions--a comparison of multiple
      cell lines.
AB  - AIM: The differentiation efficiencies of human embryonic stem cell (hESC) lines
      differ from each other. To assess this in more detail we studied the cardiac
      differentiation of eight hESC lines derived in the same laboratory. RESULTS:
      Substantial variation in growth and in the ability to form beating areas was seen
      between the different hESC lines; line HS346 gave the best efficiency (9.4%),
      while HS293 did not differentiate into beating colonies at all. Nine germ layer
      and differentiation markers were quantified during early differentiation in four
      hESC lines. The expression levels of Brachyury T, MESP1 and NKX2.5 were highest
      in the most efficient cardiac line (HS346). A systematic characterization of the
      beating cells revealed proper cardiac marker expression, electrophysiological
      activity, and pharmacological response. CONCLUSIONS: The hESC lines derived in
      the same laboratory varied considerably in their potential to differentiate into
      beating cardiomyocytes. None of the expression markers could clearly predict
      cardiac differentiation potential, although the expression of early
      cardiomyogenic genes was upregulated in the best cardiac line. The proper
      cardiomyocyte characteristics and pharmacological response indicate that these
      cells could be used as a model for human cardiomyocytes in pharmacological and
      toxicological analyses when investigating new heart medications or cardiac side
      effects.

PMID- 19165644
TI  - Early detection of oxidized surfaces using Shewanella oneidensis MR-1 as a tool.
AB  - Corrosion is a natural global problem of immense importance. Oxidation of iron
      and steel not only compromises the structural stability of a widely used and
      versatile material but it also creates an abrasive compound (iron oxide) that can
      score the surfaces of metals, rendering them useless for the purpose for which
      they were designed. Clearly, the identification of corrosion in its nascent
      stages is a high priority for reasons that range from aesthetics to economics.
      Many bacteria in the facultatively aerobic genus Shewanella have the capacity to
      respire some metal oxides, such as iron oxide, by way of a variety of oxide
      binding proteins lodged in their outer membrane. In this study, a rapid, cost
      effective system for the specific early detection of a variety of oxidized steel
      surfaces is described, taking advantage of bacteria with natural affinities for
      iron oxides, to identify the sites of nascent corrosion.

PMID- 19165645
TI  - Experience with the Impella recovery axial-flow system for acute heart failure at
      three cardiothoracic centers in Sweden.
AB  - OBJECTIVES: The Impella recovery axial-flow system is a mechanical assist system
      for use in acute heart failure. This retrospective study reports the use of the
      device at three cardiothoracic units in Sweden. DESIGN: Fifty patients (35 men,
      mean age 55.8 years, range 26 to 84 years) underwent implantation of 26 ImpellaLP
      2.5/5.0 (support-time 0.1 to 14 days), 16 ImpellaLD (support-time 1 to 7 days)
      and 8 ImpellaRD (support-time 0.1 to 8 days) between 2003 and 2007. Implantation
      was performed because of postcardiotomy heart failure (surgical group, n=33) or
      for various states of heart failure in cardiological patients (non-surgical
      group, n=17). The intention for the treatments was mainly to use the pump as a
      "bridge-to-recovery". RESULTS: Early mortality in the surgical and non-surgical
      groups was 45% and 23%, respectively. Complications included infection, 36% and
      right ventricular failure, 28%. Cardiac output and cardiac power output
      postoperatively were significantly higher among survivors than non-survivors.
      CONCLUSIONS: The Impella recovery axial-flow system facilitates treatment in
      acute heart failure. Early intervention in patients with acute heart failure and
      optimized hemodynamics in the post-implantation period seem to be of importance
      for long-term survival. Insufficient early response to therapy should urge to
      consider further treatment options.

PMID- 19165647
TI  - Dyslipidaemia and lipoprotein pattern in systemic lupus erythematosus (SLE) and
      SLE-related cardiovascular disease.
AB  - OBJECTIVE: This study focused on lipoprotein composition and properties in
      systemic lupus erythematosus (SLE). METHODS: The size distribution of plasma
      lipoproteins was studied by nuclear magnetic resonance (NMR). Cholesteryl ester
      transfer protein (CETP) activity was determined by enzyme-linked immunosorbent
      assay (ELISA). The affinity of low density lipoprotein (LDL) for proteoglycans
      was assayed. Twenty-six women (aged 52+/-8.2 years) with SLE and a history of
      cardiovascular disease (CVD) (SLE cases) were compared with 26 age-matched women
      with SLE and without CVD (SLE controls) and 26 age-matched population-based
      control women (controls). RESULTS: Very low density lipoprotein (VLDL) particles
      (nmol/L) were more prevalent among SLE cases than SLE controls (0.039) and tended
      to be more common in SLE cases than in controls (p = 0.073). By contrast, high
      density lipoprotein (HDL) particles (nmol/L) were more prevalent among controls
      than SLE cases (p = 0.024) whereas the number of LDL particles (nmol/L) did not
      differ significantly. Small dense (sd)LDL (nmol/L) were more common in controls
      and tended to be more common in SLE cases than in SLE controls (p = 0.036 and
      0.086, respectively). Small high density lipoproteins (sHDL) (nmol/L) were more
      prevalent in controls than in SLE controls and SLE cases (p = 0.002 and p<0.001,
      respectively). VLDL or LDL size (nm) did not differ significantly between groups
      (data not shown) whereas HDL size (nm) was increased among SLE controls as
      compared to controls (p = 0.024) and tended to be increased among SLE cases as
      compared to controls (p = 0.070). The affinity of LDL for proteoglycans or CETP
      activity did not differ between groups (data not shown). CONCLUSIONS: sdLDL was
      not increased and SLE cases and SLE controls had decreased levels of sHDL. VLDL
      differentiates between SLE cases and SLE controls. The lipid pattern in SLE
      related CVD was thus not similar to the pattern seen in diabetes or in CVD in
      general.

PMID- 19165648
TI  - A randomized, multicentre, double-blind, parallel-group study to assess the
      adverse event-related discontinuation rate with celecoxib and diclofenac in
      elderly patients with osteoarthritis.
AB  - OBJECTIVE: To compare the adverse event (AE)-related discontinuation rate with
      celecoxib vs. diclofenac when given to reduce joint pain associated with knee or
      hip osteoarthritis (OA) in elderly patients. METHODS: This was a double-blind,
      randomized, multicentre, parallel-group, 1-year comparison of celecoxib 200 mg
      once daily and diclofenac 50 mg twice daily in 925 patients with OA aged > or =
      60 years. Study visits were at baseline and at 4, 13, 26, 39, and 52 weeks. At
      each visit, the Patient's and Physician's Global Assessment of Arthritis (PaGAA,
      PhGAA), the Patient's Assessment of Arthritis Pain--Visual Analogue Scale (PAAP
      VAS), and AEs were assessed. A concomitant health economic analysis was conducted
      throughout. RESULTS: The rate of study discontinuation due to AEs, laboratory
      abnormalities, and deaths was 27% for celecoxib and 31% for diclofenac (p =
      0.22). The results of the arthritis/pain efficacy assessments were similar for
      celecoxib and diclofenac. Significantly fewer patients in the celecoxib group
      than the diclofenac group experienced cardiovascular/renal AEs (70/458 vs.
      95/458, p = 0.039) or hepatic AEs (10/458 vs. 39/458, p<0.0001). Medication costs
      were higher for celecoxib than diclofenac but mean total treatment cost was
      slightly higher in the diclofenac group. CONCLUSION: Treatment with celecoxib 200
      mg once daily and diclofenac 50 mg twice daily resulted in similar rates of AE
      related study discontinuation in elderly patients with OA. Celecoxib and
      diclofenac demonstrated comparable efficacy in relieving the signs and symptoms
      of OA. However, the proportion of patients with cardiorenal and hepatic AEs was
      significantly lower in the celecoxib group than the diclofenac group.

PMID- 19165649
TI  - Immunohistological features of hip synovitis in ankylosing spondylitis with
      advanced hip involvement.

PMID- 19165650
TI  - The effects of a vitality training programme on psychological distress in
      patients with inflammatory rheumatic diseases and fibromyalgia: a 1-year follow
      up.

PMID- 19165651
TI  - Neural correlates of inference-driven attention in perceptual and symbolic tasks:
      an event-related potential study.
AB  - The inferential system anticipates the external environment by building up
      internal representations of its regularities. To that purpose, two sources of
      information are especially important and attract attentional resources: expected
      and unexpected events, which are useful for checking the accuracy of internal
      representations. In the present study, we investigated the behavioural properties
      and the neural mechanisms underlying the strategic allocation of attention
      triggered by those events. To that end, event-related potentials (ERPs) were
      recorded during the performance of two tasks requiring detection of predictable
      and unpredictable response events embedded in a visuospatial or numeric sequence.
      The behavioural results in the two tasks mirror each other, suggesting the
      recruitment of similar attentional allocation processes between the two domains.
      The ERPs showed partially similar effects. In both tasks, a P3a-like component
      signalled the capture of attention by events clashing with previous expectations,
      whilst a P3b-like component marked the focusing of attention on predicted events
      and its redistribution among all possible response events occurring after the
      detection of an unexpected event.

PMID- 19165652
TI  - People think about what is true for conditionals, not what is false: only true
      possibilities prime the comprehension of "if".
AB  - We report the results of two priming experiments that examine the comprehension
      of conditionals--for example, "if there are apples then there are oranges"--and
      biconditionals--for example, "if and only if there are apples then there are
      oranges". The first experiment showed that participants read a biconditional
      faster when it was primed by a true possibility, "there were apples and there
      were oranges" than when it was primed by a false possibility, "there were no
      apples and there were oranges"; a conditional was primed equally by both
      possibilities. The second experiment showed that participants read the negated
      antecedent conjunction faster when it was primed by a conditional than when it
      was primed by a biconditional; the affirmative conjunction was primed equally by
      both connectives. The experiments show that (a) when people understand "if A then
      B", they access the true possibilities, "A and B", and "not-A and B", and (b)
      when they understand "if and only if A then B" they access "A and B", but they do
      not access "not-A and B". We discuss their implications for current theories of
      reasoning.

PMID- 19165653
TI  - Worsening of bruxism with atomoxetine: a case report.
AB  - Atomoxetine is the only FDA-approved non-stimulant to treat ADHD. We report a
      case of Atomoxetine-related exacerbation of nocturnal bruxism in a 12-yr old boy
      with ADHD, subsiding on discontinuing the drug, but re-worsening with retrial,
      finally subsiding upon adding Buspirone. This is the first report of its kind
      showing such an association, not included in any pre- or post-marketing data.
      Clinical implications and possible mechanisms are discussed.

PMID- 19165654
TI  - Food groups and risk of forearm fractures in postmenopausal women in Chengdu,
      China.
AB  - BACKGROUND: Forearm fractures are a major cause of disability in postmenopausal
      women. However, no prior report on the relationship of dietary patterns and
      forearm fracture in mainland China is available and the results from Western
      studies may not be applicable to the Chinese population. OBJECTIVE: To determine
      whether food groups are associated with the risk of forearm fracture among
      postmenopausal women in China. Design Case-control study. METHODS: Cases were 209
      postmenopausal women aged 50-70 years with new forearm fractures, identified in
      hospitals in Chengdu. Controls were age- and district-matched subjects randomly
      selected from the community of Chengdu. Dietary habits and food group intake were
      measured by a structured food frequency questionnaire. RESULTS: The dietary
      pattern in Chinese postmenopausal women was of high intakes of cereals,
      vegetables, fruits, beans or bean products, but lower intakes of meat and milk.
      The estimated odds ratios (95% confidence intervals) for forearm fracture were
      0.53 (0.42-0.67) for each quintile increase in vegetable intake, 0.73 (0.59-0.92)
      for each quintile increase in cereal intake, and 0.26 (0.14-0.48) in subjects who
      met World Health Organization (WHO) dietary recommendations for vegetables and
      fruits. CONCLUSIONS: This is the first report indicating that the levels of
      vegetable and cereal intake, and that meeting WHO recommendations for vegetable
      and fruit intake, are associated with a decrease in the risk of forearm fractures
      in Chinese postmenopausal women.

PMID- 19165655
TI  - Sex, fat and breast cancer.

PMID- 19165656
TI  - Adverse effects of excessive ovarian response on the pregnancy rate of in vitro
      fertilization treatment.

PMID- 19165657
TI  - Mayer-Rokitansky-Kuster-Hauser syndrome: recent clinical and genetic findings.
AB  - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by Mullerian duct
      aplasia in an XX individual with female phenotype presenting primary amenorrhea
      at adolescence. Multiple abnormalities may be associated with the MRKH syndrome.
      Genetic investigations focused on the genes of anti-Mullerian hormone and its
      receptor, as well as on Wt1, Pax2, Cftr and Hox genes, have been unproductive.
      Only the Wnt4 gene has been clearly implicated in MRKH syndrome and found to be
      associated with clinical and/or biological signs of hyperandrogenism in three
      different works. Beside the multiple malformations that may be associated with
      MRKH syndrome, such as renal, skeletal, cardiac and auditory defects, MRKH and
      hyperandrogenism represent a new clinical and genetic disorder.

PMID- 19165658
TI  - Testosterone replacement therapy in the climacteric: benefits beyond sexuality.
AB  - Testosterone therapy during menopause has a wide range of benefits that reach
      beyond the realm of human sexuality. This is a consequence not only of the
      widespread distribution of androgen receptors in various extragonadal tissues but
      also of the conversion of androgens to estrogens in the tissues in which
      aromatase expression is present. For this reason, testosterone therapy during the
      climacteric years will not only supply androgens but will also stimulate estrogen
      production in tissues that express aromatase. Furthermore, the bioavailability of
      androgens to the tissues depends not only on the rate of their production by the
      postmenopausal ovaries and adrenals but also on the circulating levels of sex
      hormone-binding globulin (SHBG). Tibolone inhibits SHBG production in the liver,
      thus increasing free testosterone levels. The association of tibolone with
      testosterone as a form of androgen replacement therapy during the climacteric is
      discussed, as is the use of low-dose testosterone, tibolone or the association of
      both in perimenopausal patients with signs of androgen deficiency. Testosterone
      treatment has a boosting effect not only on human sexuality but also on the
      sensation of well-being, a stimulatory effect conferred by the increase in beta
      endorphins.

PMID- 19165659
TI  - Cimicifuga racemosa treatment and health related quality of life in post
      menopausal Spanish women.
AB  - OBJECTIVE: The effect of Cimicifuga racemosa (CR) treatment was evaluated in
      healthy symptomatic post-menopausal women using the Cervantes health-related
      quality of life (HR-QoL) scale. DESIGN: A prospective observational study was
      carried out in 122 healthy symptomatic post-menopausal Spanish women with
      elevated body weight, aged between 45 and 59 years. Three groups were formed
      according to age intervals. Each patient completed the Cervantes HR-QoL scale
      before and after CR treatment (20 mg, twice a day for 3 months). Changes in
      Cervantes scale global quality of life scores as well as in their domains
      (menopause and health, psychic, sexuality and couple relationship) were analysed.
      RESULTS: The CR treatment ameliorated global quality of life in both the whole
      group of patients and when women were analysed by age subgroups. There were
      significant positive changes in Z scores for the Cervantes HR-QoL scale
      'menopause and health', and 'psychic' domains in both the entire population and
      by age groups. The 'sexuality domain' significantly improved when the entire
      population was assessed, but not when each age-group was separately analysed;
      while there were no changes in 'couple relationship domain' scores. CONCLUSION:
      CR treatment increased both global quality of life and the four domains of the
      Cervantes HR-QoL scale, being an effective treatment to reduce symptoms in post
      menopausal woman with elevated body weight.

PMID- 19165660
TI  - Relationship between serum adipocytokine levels and metabolic syndrome in
      menopausal women.
AB  - OBJECTIVE: Adipocytokines are bioactive substances derived from adipose tissues,
      especially visceral fat, and play a crucial role in the development of metabolic
      syndrome. The aims of this study were to estimate serum levels of adipocytokines
      (adiponectin, resistin and TNF-alpha) and to examine the associations between
      adipocytokine levels and metabolic syndrome in menopausal women. METHODS: We
      recruited 28 postmenopausal women with features of metabolic syndrome. For the
      purpose of comparing adipocytokine levels, 30 postmenopausal women without
      metabolic syndrome were recruited by matching age and body mass index (BMI).
      Serum levels of adipocytokines (adiponectin, resistin, TNF-alpha) were then
      determined, and any potential correlations between adipocytokine levels and
      metabolic syndrome were investigated. RESULTS: There were no significant
      differences in adiponectin or resistin levels in women with metabolic syndrome
      when compared with the control group. Conversely, TNF-alpha levels were
      significantly higher in women with metabolic syndrome. Furthermore, multivariate
      logistic regression analysis indicated that TNF-alpha was significantly
      associated with metabolic syndrome. CONCLUSION: Our results suggest that, among
      the adipocytokines (adiponectin, resistin and TNF-alpha), serum TNF-alpha levels
      may serve as a useful biomarker for diagnosing metabolic syndrome in menopausal
      women.

PMID- 19165661
TI  - Effects of phytoestrogens genistein and daidzein on progesterone and estrogen
      (estradiol) production of human term trophoblast cells in vitro.
AB  - OBJECTIVE: Phytoestrogens are a diverse group of nonsteroidal plant compounds
      that occur naturally in many plants. Because they possess a ring system similar
      to estrogens they are able to bind on estrogen receptors alpha and beta in
      humans. The effects of the phytoestrogens genistein and daidzein on the
      production of progesterone and estrogen in isolated human term trophoblast cells
      in vitro were tested in this study. MATERIAL AND METHODS: Cytotrophoblast cells
      were isolated from human term placentas. Phytoestrogens genistein and daidzein
      were incubated in different concentrations with trophoblast cells. Untreated
      cells were used as controls. After 24 h aliquots were removed and tested for
      progesterone and estrogen production. RESULTS: The production of the steroid
      hormones progesterone and estrogen are influenced by phytoestrogens genistein and
      daidzein in human term trophoblast cells. A strong inhibition effect of both
      phytoestrogens tested in the production of progesterone was demonstrated. In
      addition, a significant stimulating effect on estrogen production by genistein
      and daidzein was observed. CONCLUSION: Results obtained with this study show that
      phytoestrogens (genistein and daidzein) sufficiently reduce progesterone
      production in human term trophoblast cells. Because blockade of progesterone is a
      possible mechanism involved in initiation of labor, we may speculate that high
      doses of phytoestrogens at the feto-maternal interphase could play a negative
      role in maintenance of pregnancy. Stimulation of estrogen production by genistein
      and daidzein in trophoblast cells is probably due to estrogen receptor blocking
      effects of both phytoestrogens. Trophoblast cells seem to compensate blocking of
      its estrogen receptors by higher estrogen production.

PMID- 19165662
TI  - The role of iron in the pathogenesis of endometriosis.
AB  - BACKGROUND: Endometriosis may cause symptoms including chronic pelvic pain and
      infertility, and increases susceptibility to the development of ovarian cancer.
      Genomic studies have started to delineate the wide array of mediators involved in
      the development of endometriosis. Understanding the mechanisms of endometriosis
      development and elucidating its pathogenesis and pathophysiology are intrinsic to
      prevention and the search for effective therapies. METHOD OF STUDY: The present
      article reviews the English language literature for biological, pathogenetic and
      pathophysiological studies on endometriosis. Several recent genomic studies are
      discussed in the context of endometriosis biology. RESULTS: Severe hemolysis
      occurring during the development of endometriosis results in high levels of free
      heme and iron. These compounds oxidatively modify lipids and proteins, leading to
      cell and DNA damage, and subsequently fibrosis development. Recent studies based
      on genome-wide expression analysis technology have noted specific expression of
      heme/iron-dependent mediators in endometriosis. The heme/iron-dependent signaling
      pathway of endometriosis, which is providing new insights into the regulation of
      inflammation, detoxification and survival, is discussed. CONCLUSION: Several
      important endometriosis-specific genes overlap with those known to be regulated
      by iron. Other genes are involved in oxidative stress. Iron has a significant
      impact on endometriotic-cell gene expression. This review summarizes recent
      advances in the heme/iron-mediated signaling and its target genes, outlines the
      potential challenges to understanding of the pathogenesis and pathophysiology of
      endometriosis, and proposes a possible novel model.

PMID- 19165663
TI  - Low-dose human chorionic gonadotropin during the proliferative phase may
      adversely affect endometrial receptivity in oocyte recipients.
AB  - The effect of low-dose human chorionic gonadotropin (hCG) administration in the
      proliferative phase of oocyte recipients was investigated in a prospective
      randomized trial. Sibling oocytes from the same donor were shared at random among
      two different recipients. In group I oocyte recipients received 750 IU of hCG
      every three days concomitant to endometrial preparation with estradiol until hCG
      injection to the donor, whereas in group II recipients received no hCG during
      endometrial priming with estradiol. Endometrial thickness was significantly lower
      in group I compared with group II, although similar endometrial thickness was
      detected during the mock cycle. Pregnancy rates were significantly lower in group
      I than in group II (13.6% vs. 45.4%, p<0.05). Implantation rates were also
      significantly lower in group I (1.7% vs. 22.4%, p<0.01). The study was
      discontinued prematurely for ethical reasons when 22 cycles were completed, as
      pregnancy rates were very low in group I. In conclusion, hCG administration in
      the proliferative phase might directly affect endometrial proliferation and
      receptivity.

PMID- 19165664
TI  - Triggering with HCG or GnRH agonist in GnRH antagonist treated oocyte donation
      cycles: a randomised clinical trial.
AB  - AIM: To compare donor and recipient outcome after inducing the final oocyte
      maturation with hCG or GnRH agonist in GnRH-antagonist treated oocyte donation
      (OD) cycles. METHODS: Two-hundred fifty-seven oocyte donors were enrolled to
      participate in a clinical trial in a private fertility centre. After stimulation
      with 225 IU rFSH and Cetrorelix 0.25 mg/day, 212 oocyte donors were randomised
      with sealed envelopes for triggering with recombinant hCG (Ovitrelle 250 microgr,
      n = 106) or a GnRH agonist (triptorelin 0.2 mg, n = 106). RESULTS: The number of
      retrieved COCs (12 +/- 6.3 vs 11.4 +/- 6.4), mature oocytes (8 +/- 4.6 vs 7.5 +/-
      4.1), the proportion of mature oocytes (67.2 +/- 20.4% vs 67.1 +/- 20.9%) and
      fertilisation rates (67.8 +/- 23.5% vs 71.1 +/- 22.1%) were comparable. Clinical,
      ongoing pregnancy and live birth rates were not statistically different in the
      corresponding recipient groups. Nine cases of mild and one case of severe OHSS
      occurred in hCG group, whereas no cases were detected in GnRH agonist group.
      CONCLUSIONS: The findings of our RCT suggest that donor and recipient outcome are
      comparable in OD cycles triggered with hCG or a GnRH agonist. Furthermore, the
      risk of OHSS seems to be reduced considerably, therefore the combination of a
      GnRH antagonist protocol with GnRH agonist triggering constitutes a safe
      treatment option for egg-donors.

PMID- 19165665
TI  - In vitro fertilization is associated with an increased risk for preeclampsia.
AB  - OBJECTIVE: To assess the association of intrauterine insemination, in vitro
      fertilization (IVF) and ovulation induction with the risk of preeclampsia.
      METHODS: We conducted a population based retrospective cohort study of
      pregnancies conceived by assisted reproductive technology (1357 exposure
      subjects, 5190 controls) based on 2005 Niday Perinatal Database for Ontario,
      Canada. All pregnancies conceived by assisted reproductive technology were
      identified as exposure group. Four controls were randomly matched for each
      exposure subject by maternal age, parity, plurality, and delivery hospital level
      and residence area. The risks for preeclampsia associated with intrauterine
      insemination, IVF, and ovulation induction were evaluated through conditional
      logistic regression models compared with their corresponding controls. RESULTS:
      With adjustment of maternal age, smoking during pregnancy and initiating time of
      prenatal care, in vitro fertilization was associated with an increased risk for
      preeclampsia (OR=1.78, 95% CI: 1.05, 3.06), whereas intrauterine insemination
      (OR=2.44, 95% CI: 0.74, 8.06) and ovulation induction (OR=1.34, 95% CI: 0.31,
      5.75) was not associated with the risk for preeclampsia. CONCLUSION: There was a
      higher incidence of preeclampsia among pregnancies conceived by IVF, but no
      significant association was found in intrauterine insemination and ovulation
      induction.

PMID- 19165666
TI  - Plasma homocysteine concentrations and insulin resistance in preeclampsia.
AB  - The correlation between insulin resistance and homocysteine levels in patients
      with preeclampsia indicate that insulin resistance in preeclampsia is related to
      endothelial dysfunction.

PMID- 19165667
TI  - Doppler measurement of renal interlobar vein impedance index in uncomplicated and
      preeclamptic pregnancies.
AB  - OBJECTIVE: To define normal values of Renal interlobar vein impedance index
      (RIVI) throughout gestation, as a reference to RIVI in preeclampsia (PE).
      METHODS: Longitudinal evaluation of 20 uncomplicated pregnancies (UP) by standard
      renal duplex scan, every 4 weeks during pregnancy and postpartum. Comparison of
      RIVI between 40 PE and UP, and plotting of PE values against the normal reference
      range at corresponding gestation. RESULTS: In PE, RIVI is significantly higher
      than in UP, the difference being larger at the left side and in cases of
      preeclampsia remote from term. CONCLUSION: Increase of RIVI in women with PE is
      gestation-dependant.

PMID- 19165668
TI  - Postpartum cerebral angiopathy mimicking hypertensive putaminal hematoma: a case
      report.
AB  - OBJECTIVE: To present an emerging clinical entity which may mimic another common
      entity. METHODS: A 31 year-old woman complained of sudden severe headache and
      collapsed. She had delivered by Cesarean section one week previously. She had a
      normal antenatal history and did not have any evidence of hypertension. RESULTS:
      Clinical examination revealed her to be in altered sensorium, GCS E2V2M5 with
      reduced movements on the left side. CT scan showed a large right putaminal
      hematoma with mass effect and midline shift. MRI also showed the hematoma but the
      MRV was normal. Despite antiedema measures and hyperventilation, the patient
      continued to deteriorate and so underwent right hemicraniectomy. MRA was done
      postoperatively and showed diffuse spasm of both middle cerebral arteries. A
      diagnosis of postpartum cerebral angiopathy was made and she was put on
      methylprednisolone and other antiedema measures were continued. With this she
      improved significantly. At one year she had residual hemiparesis but had returned
      to work. Four-vessel angiogram repeated 1 year later showed no arterial spasm.
      She later had cranioplasty to cover the defect. CONCLUSIONS: This case is
      presented to show that in a postpartum patient, if she presents with putaminal
      hematoma, postpartum angiopathy needs to be suspected and appropriate
      investigations and treatment, including steroids, should be given as the overall
      prognosis is good.

PMID- 19165669
TI  - Hemodynamically-directed atenolol therapy is associated with a blunted rise in
      maternal sFLT-1 levels during pregnancy.
AB  - OBJECTIVE: Cardiac output and sFlt-1 are elevated prior to clinical evidence of
      preeclampsia. Early treatment of high cardiac output with atenolol decreases the
      risk for preeclampsia. We hypothesized that atenolol would impact circulating
      sFlt-1. METHODS: Cardiac output and plasma sFlt-1 were measured <or=24 weeks'
      gestation and every 6 to 8 weeks in a longitudinal pilot study of: 1) women with
      risk factors for preeclampsia (high-risk group; n=46) who were treated with
      atenolol, and 2) low-risk group (control, n=25) who were not treated. RESULTS:
      The groups were similar in maternal age (mean+/-SD: high-risk 28.3+/-5.4 versus
      control 30.3+/-5.5 years) and enrollment gestational age (17.3+/-4.3 versus
      16.1+/-4.2 weeks). The high-risk group had higher cardiac output (9.7+/-1.7
      versus 7.3+/-1.7 L/min; p<0.001) and mean arterial pressure (91.8+/-10.6 versus
      79.6+/-7.3 mm Hg; p<0.001). Cardiac output and mean arterial pressure decreased
      while sFlt-1 levels rose less in the high-risk group compared with controls
      (p=0.001 for all using GEE) even after adjusting for preeclampsia risk factors
      (age, weight, and primigravida status). CONCLUSION: Atenolol in high-risk women
      was associated with a lower rise in sFlt-1, suggesting an effect of
      hemodynamically directed treatment on the anti-angiogenic state.

PMID- 19165670
TI  - Interactions between inflammatory and oxidative stress in preeclampsia.
AB  - OBJECTIVE: Oxidative stress and a generalized inflammatory state are features of
      preeclampsia (PE). The objective of this study was to compare the levels of
      products of inflammatory reaction and oxidative stress markers in patients with
      PE, and to determine the relationship between oxidative stress and inflammation
      in PE. METHODS: Plasma concentrations of high-sensitive C-reactive protein (hs
      CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha),
      malondialdehyde (MDA), and 8-isoprostane were measured in 53 women with PE and 20
      age- and BMI-matched normotensive women. RESULTS: The plasma concentrations of hs
      CRP, IL-6, TNF-alpha, and 8-isoprostane were significantly higher in women with
      PE than in those with normotensive pregnancies, and these parameters, except for
      8-isoprostane, were markedly elevated in those with severe PE (SPE), rather than
      mild PE (MPE). Moreover, plasma levels of 8-isoprostane, not MDA, were
      significantly correlated with the plasma levels of hs-CRP, IL-6, and TNF-alpha in
      patients with PE. CONCLUSIONS: These findings suggest that oxidative stress and
      inflammatory reaction are closely associated with PE, and the interactions
      between them may participate in the pathogenesis of PE.

PMID- 19165671
TI  - Timing of indicated delivery after antenatal steroids in preterm pregnancies with
      severe hypertension.
AB  - OBJECTIVES: To evaluate the effect of the time interval between administering
      antenatal steroids needed to accelerate fetal lung maturity and indicated
      delivery in preterm pregnancies complicated by severe hypertension, as determined
      by maternal and perinatal outcomes. METHODS: The Nova Scotia Atlee Perinatal
      Database was used to identify a population-based cohort of women with severe
      hypertension who delivered an infant between 1989 and 2002. Women were included
      if they received antenatal steroids and required delivery between 26 and 34 weeks
      gestation. Multivariate logistic regression analyses were conducted to evaluate
      the effect of time interval on maternal and perinatal mortality, maternal
      hemorrhagic and hypertension-associated morbidity, and perinatal respiratory,
      infectious, and prematurity-associated morbidity, while controlling for
      confounding variables. RESULTS: 172 pregnancies satisfied inclusion and exclusion
      criteria. Betamethasone was the most commonly used corticosteroid to accelerate
      fetal lung maturity (95%). Among infants delivered at 26 to 34 weeks, adjusted
      analyses showed a reduction in risk of depression at birth (RR, 0.54; 95% CI,
      0.24 to 0.97) and need for surfactant (RR, 0.50; 95% CI, 0.25 to 0.95) when the
      time interval from steroid administration to delivery was >48 hours compared with
      <or= 48 hours. Adjusted analyses in a subgroup of women with cesarean delivery
      (81% of deliveries) demonstrated no differences in rates maternal or neonatal
      morbidity. CONCLUSIONS: The rates of most adverse maternal and neonatal outcomes
      in preterm pregnancies with severe hypertension delivered at 26 to 34 weeks are
      not affected by timing from steroid administration to delivery. These data
      support the decision for delivery based mainly on obstetrical indications.

PMID- 19165672
TI  - Utilization of health care services of pregnant women complicated by preeclampsia
      in Ontario.
AB  - OBJECTIVE: To assess the utilization of health care services by pregnant women
      affected by preeclampsia (PE). DESIGN: Population-based study. SETTING: Perinatal
      partnership hospitals in Ontario. POPULATION: Obstetric deliveries in 2005
      Canadian province of Ontario (about 95% of births). METHODS: For each PE case,
      four subjects without PE matched by age, parity, plurality, and hospital at
      childbirth were chosen as the controls. We compared the utilization of intra
      partum care services and infant outcomes between the two groups. We also
      estimated the extra costs to the health care system in Ontario for caesarean
      delivery and caring of extremely low birth weight infants attributable to PE
      during the neonatal period and in the first 2 years of life. MAIN OUTCOME
      MEASURES: Cesarean delivery, hospital stay, extremely low birth weight infants,
      cost. RESULTS: Of the 120,611 obstetric deliveries included in this analysis,
      1240 (1.3%) were diagnosed with PE. Patients with PE and matched controls were
      similar in maternal age, parity, and other demographic characteristics. Compared
      with study subjects without PE, those with PE had increased uses of spinal
      anesthesia, maternal transfer, Cesarean delivery, labour induction, neonatal
      transfer, newborn resuscitation, longer hospital stay for childbirth, and higher
      rates of preterm births and low birth weight. The extra costs to the health care
      system for cesarean delivery and caring of extremely low-birth-weight infants
      attributable to PE during the neonatal period and in the first 2 years of life in
      Ontario were $0.5 millions, 3.1 millions, and $5.1 million per year,
      respectively, if we use the reported PE rate in this database. CONCLUSION: PE is
      associated with substantially increased costs to the health care system.

PMID- 19165674
TI  - Serum sFlt1:PlGF ratio, PlGF, and soluble endoglin levels in gestational
      proteinuria.
AB  - OBJECTIVE: It was recently reported that both a high soluble fms-like tyrosine
      kinase 1 (sFlt1): placental growth factor (PlGF) ratio (sFlt1:PlGF ratio) and
      high soluble endoglin (sEng) levels are related to the later occurrence of
      preeclampsia. We compared the serum sFlt1:PlGF ratio, PlGF and sEng levels in
      women with gestational proteinuria (GP) to those in women with preeclampsia.
      METHODS: Seven women with GP and 34 women with preeclampsia were recruited in
      this study. The 95(th) percentile values in the reference curves of sFlt1,
      sFlt1:PlGF ratio and sEng, and the 5(th) percentile values in the reference curve
      of PlGF were respectively set as the cutoff values. RESULTS: The incidence rates
      of a high sFlt1:PlGF ratio, low PlGF and high sEng in women with GP were 57%, 29%
      and 86%, respectively, whereas those in women with preeclampsia were 94%, 77%,
      and 88%, respectively (p=0.028, p=0.024, and p=1.000, respectively). The
      incidence rates of a both high sFlt1:PlGF ratio and high sEng in women with GP
      and preeclampsia were 57% and 88%, respectively (p=0.082). CONCLUSION: The
      majority of women with GP showed both increases of the sFlt1:PlGF ratio and sEng,
      thus suggesting some women with GP may represent subclinical preeclampsia. In
      addition, women with GP showed a significantly lower sFlt1:PlGF ratio and higher
      PlGF level than those with preeclampsia, suggesting that the PlGF level is a key
      regulator for developing hypertension in some pregnant women, even with increases
      of both sFlt1:PlGF ratio and sEng levels.

PMID- 19165673
TI  - Genetic thrombophilia variants and risk for preeclampsia among American Indians.
AB  - OBJECTIVE: To determine the prevalence of thrombophilic genetic variants in an
      American Indian population and determine if they are associated with
      preeclampsia. METHODS: A total of 87 cases, 165 controls and an additional 75
      population-based controls were genotyped for two thrombophilic polymorphisms.
      RESULTS: The allelic prevalence of the factor V Leiden and 20210 G/A prothrombin
      variants in this population was 2.1% and 0.5% respectively. No statistically
      significant associations between these genetic variants and preeclampsia were
      found. CONCLUSION: The prevalence of thrombophilic variants is of possible public
      health significance for other morbidity; but perhaps not in relation to
      preeclampsia.

PMID- 19165675
TI  - Correlation of 2-hour and 4-hour urinary proteins with 24-hours proteinuria in
      hospitalized patients with preeclampsia.
AB  - OBJECTIVE: To determine whether 2-hour and 4-hour urinary proteins correlate with
      24-hour proteinuria in patients with preeclampsia. STUDY DESIGN: Protein
      estimation was done from 2-hour, 4-hour, and 24-hour urine samples in 50 women
      with preeclampsia and the results were compared. RESULTS: Statistical analysis
      demonstrated no significant difference in the mean protein excretion when
      comparing the 2-hour values with the 24-hour and further comparing 4-hour values
      with the 24-hour value. The values of 2-hour and 4-hour urine proteins in total
      volume (TV) correlated well with 24-hour value for mild & severe disease
      (p<0.001). Amount of the protein excretion in 2-hour and 4-hour samples predicted
      mild preeclampsia with positive predictive value of 100% and negative predictive
      value (NPV) of 80%. NPV of both the samples for severe preeclampsia was 100%.
      CONCLUSION: 2-hour and 4-hour proteinuria can be used for initial assessment of
      preeclampsia thereby avoiding the inconvenience and delay in treatment.

PMID- 19165676
TI  - What is SNOMED CT and why should the ISSHP care?
AB  - SNOMED CT (Systematized NOmenclature of MEDicine Clinical Terms) is a
      standardized multilingual healthcare terminology. It was developed to meet the
      needs of our electronic world so that care can be documented and clinicians can
      retrieve and transmit data in electronic format. It is anticipated that SNOMED CT
      will provide the core general terminology for electronic health records and, as
      such, replace existing classification systems such as the International
      Statistical Classification of Diseases and Related Health Problems 10th Revision
      (ICD-10). At present, there is no special interest group for the hypertensive
      disorders of pregnancy (HDP) within the SNOMED CT initiative. We believe that
      members of the ISSHP, and others interested in the HDP, should take a leadership
      role in this regard for a number of reasons.

PMID- 19165677
TI  - Systems Biology in Reproductive Medicine. Invited oral presentations.

PMID- 19165678
TI  - Fetal biometry: a comparison between experienced sonographers and automated
      measurements.
AB  - OBJECTIVE: We compared the performance between sonographers and automated fetal
      biometry measurements (Auto OB) with respect to the following measurements:
      biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC)
      and femur length (FL). METHODS: The first set of experiments involved assessing
      the performance of Auto OB relative to the five sonographers, using 240 images
      for each user. Each sonographer made measurements in 80 images per anatomy. The
      second set of experiments compared the performance of Auto OB with respect to the
      data generated by the five sonographers for inter-observer variability (i.e.,
      sonographers and clinicians) using a set of 10 images per anatomy. RESULTS: Auto
      OB correlated well with manual measurements for BPD, HC, AC and FL (r > 0.98, p <
      0.001 for all measurements). The errors produced by Auto OB for BPD is 1.46%
      (sigma = 1.74%), where sigma denotes standard deviation), for HC is 1.25% (sigma
      = 1.34%), for AC is 3% (sigma = 6.16%) and for FL is 3.52% (sigma = 3.72%). In
      general, these errors represent deviations of less than 3 days for fetuses
      younger than 30 weeks, and less than 7 days for fetuses between 30 and 40 weeks
      of age. CONCLUSION: The measurements produced by Auto OB are comparable to the
      measurements done by sonographers.

PMID- 19165679
TI  - Cerebrovascular diseases during pregnancy and puerperium.
AB  - OBJECTIVE: We have studied 37 women with all forms of cerebrovascular diseases.
      Our aim was to study the etiology, clinical manifestations and prognosis of such
      conditions during pregnancy or puerperium. METHODS: We analyzed the most common
      causes of cerebrovascular diseases during the given period. RESULTS: The most
      common causes of cerebrovascular diseases during pregnancy or puerperium are
      hematological coagulation disorders, cardio embolism and eclampsia, whereas other
      causes ara rarer. CONCLUSIONS: The incidence of cerebrovascular diseases during
      pregnancy or puerperium is 11%. Cerebrovascular diseases are more frequent in
      puerperium than during pregnancy, being 1.8:1. Etiology remains undetermined in
      35% of the cases.

PMID- 19165680
TI  - Quantitative detection of EP3-II, III and VI messenger RNA in gravid and non
      gravid human myometrium using real-time RT-PCR.
AB  - OBJECTIVE: To examine mRNA expression of prostaglandin E2 receptor isoforms EP3
      II, III and VI in lower uterine segment myometrium in the non-pregnant and
      pregnant state using quantitative real-time RT-PCR. METHODS: Myometrial samples
      were obtained at the time of cesarean delivery or hysterectomy. Pregnant subjects
      were categorised based on the presence or absence of labour. Labour was defined
      as regular uterine contractions resulting in cervical change. Quantification for
      EP3 isoforms II, III and VI mRNA was performed using real-time RT-PCR. RESULTS:
      There were no differences between non-pregnant and non-labouring pregnant
      subjects in mRNA expression of EP3-II, III and VI. However, when compared to
      pregnant subjects not in labour, labouring subjects had a 3.8-fold reduction in
      EP3-II expression (p < 0.001) and 5.3-fold reduction in EP3-VI expression (p =
      0.022). CONCLUSIONS: In human parturition, there is decreased mRNA expression of
      lower-uterine segment EP3 receptor isoforms II and VI during labour. This may
      reflect differential relaxation of the lower segment of the uterus allowing
      dilatation and descent of the fetus.

PMID- 19165681
TI  - A randomised controlled trial of early initiation of oral feeding after cesarean
      section.
AB  - OBJECTIVE: To evaluate the safety and efficacy of early oral feeding after
      cesarean delivery. METHODS: Two hundred women who had cesarean section were
      randomly assigned to early feeding or routine feeding. Women in the early feeding
      group were encouraged to take sips of water 8 h post-operatively, followed by
      oral tea of 100 mL at the time of supervision. Women in the routine feeding group
      were managed by restricting oral intake for the first 24 h and administration of
      sips of water 24-48 h post-operatively. The outcome measures include the rate of
      ileus symptoms, post-operative time interval to presence of bowel sounds, passage
      of flatus and bowel movement, time interval to return to regular diet, length of
      hospital stay, post-operative complications, acceptability and benefit of early
      oral feeding. RESULTS: The early feeding group had a shorter mean post-operative
      time interval to bowel sounds 18.90 +/- 4.17 h versus 36.21 +/- 3.52 h (p <
      0.001), passage of flatus 44.81 +/- 3.73 h versus 60.58 +/- 4.40 h (p < 0.001)
      and bowel movement 58.30 +/- 5.91 h versus 72.76 +/- 4.25 h (p < 0.001). There
      was no significant difference in paralytic ileus symptoms. Early feeding group
      had a shorter mean hospital stay 4.80 +/- 0.59 days versus 6.69 +/- 0.71 days (p
      = 0.001). Early feeding group required less intravenous fluid 7.14 +/- 1.34
      bottles versus 11.8 +/- 1.32 bottles (p < 0.001). CONCLUSIONS: Early feeding
      after cesarean section was well tolerated and safe and can be implemented without
      an increase in adverse outcome.

PMID- 19165682
TI  - Efficacy of tranexamic acid in reducing blood loss after cesarean section.
AB  - AIM: To assess the efficacy and safety of tranexamic acid in reducing blood loss
      at caesarian section (CS). METHOD: A prospective randomised study conducted on 90
      primiparas divided into two groups who underwent CS. The study group, 45 women,
      received tranexamic acid immediately before CS, whereas the control group, 45
      women received placebo. Blood loss volume was measured from the end of CS to 2 h
      postpartum and compared between the two groups. Hemoglobin (Hb) and hematocrit
      (Hct) were tested 24 h after CS and compared between the two groups. RESULTS:
      Tranexamic acid significantly reduced the blood loss from the end of CS to 2 h
      postpartum; 28.02 +/- 5.53 mL in the tranexamic group versus 37.12 +/- 8.97 mL in
      the control group (p = 0.000). Hb 24 h after CS was significantly greater in
      tranexamic group than control group (12.57 +/- 1.33 in the tranexamic group and
      11.74 +/- 1.14 in the control group, p = 0.002). No complications or side effects
      were reported in either group. CONCLUSIONS: Tranexamic acid statistically reduces
      blood loss from end to 2 h after CS and its use was not associated with any side
      effects or complications. Consequently, tranexamic acid can be used safely and
      effectively to reduce bleeding resulting from CS.

PMID- 19165683
TI  - Explaining 'congenital malformations'.

PMID- 19165684
TI  - Headaches among Operation Iraqi Freedom/Operation Enduring Freedom veterans with
      mild traumatic brain injury associated with exposures to explosions.
AB  - Traumatic brain injury (TBI) is a common injury type among Operation Iraqi
      Freedom/Operation Enduring Freedom (OIF/OEF) veterans, and headaches are a
      frequent consequence of TBI. We examined the hypothesis that among veterans who
      reported mild TBI caused by exposure to an explosion during deployment in
      OIF/OEF, those with residual neurocognitive deficits would have a higher
      frequency of headaches and more severe headaches. We evaluated 155 consecutive
      veterans with neurological examination and neuropsychological testing. We
      excluded 29 veterans because they did not have mild TBI or they did not complete
      the evaluation. We analyzed headache pattern, intensity, and frequency. Among the
      126 veterans studied, 80 had impairments on neurological examination or
      neuropsychological testing that were best attributed to TBI. Veterans with
      impairments had been exposed to more explosions and were more likely to have
      headache, features of migraine, more severe pain, more frequent headaches,
      posttraumatic stress disorder, and impaired sleep with nightmares.

PMID- 19165685
TI  - Quality of medical care provided to service members with combat-related limb
      amputations: report of patient satisfaction.
AB  - A group of 158 service members who sustained major limb amputations during the
      global war on terrorism were surveyed on their satisfaction with the quality of
      care received from the Walter Reed Army Medical Center (WRAMC) Amputee Clinic
      from the time of their injury to their inpatient discharge. Of these
      participants, 96% were male, 77% were Caucasian, 89% were enlisted personnel, and
      68% had sustained lower-limb amputations. WRAMC inpatient therapy, peer visitors,
      overall medical care, and pain management received particularly high satisfaction
      ratings. Age, race, rank, and level and side of amputation had little effect on
      overall satisfaction ratings. Significant differences, however, were found by
      location of injury (Iraq vs Afghanistan, Cuba, and Africa) regarding satisfaction
      with care received while in Europe and with the education process at WRAMC. Study
      findings strongly support the rehabilitation-based, integrative care approach
      designed by the U.S. military to care for service members with amputations.

PMID- 19165686
TI  - Prosthesis use in persons with lower- and upper-limb amputation.
AB  - This study identified clinical (e.g., etiology) and demographic factors related
      to prosthesis use in persons with upper- and lower-limb amputation (ULA and LLA,
      respectively) and the effect of phantom limb pain (PLP) and residual limb pain
      (RLP) on prosthesis use. A total of 752 respondents with LLA and 107 respondents
      with ULA completed surveys. Factors related to greater use (hours per day) for
      persons with LLA included younger age, full- or part-time employment, marriage, a
      distal amputation, an amputation of traumatic etiology, and an absence of PLP.
      Less use was associated with reports that prosthesis use worsened RLP, and
      greater prosthesis use was associated with reports that prosthesis use did not
      affect PLP. Having a proximal amputation and reporting lower average PLP were
      related to greater use in hours per day for persons with an ULA, while having a
      distal amputation and being married were associated with greater use in days per
      month. Finally, participants with LLA were significantly more likely to wear a
      prosthesis than those with ULA. These results underscore the importance of
      examining factors related to prosthesis use and the differential effect that
      these variables may have when the etiology and location of amputation are
      considered.

PMID- 19165687
TI  - Usage of tilt-in-space, recline, and elevation seating functions in natural
      environment of wheelchair users.
AB  - This study examined the usage of powered seating functions, including tilt-in
      space, backrest recline, and seat elevation, among a group of wheelchair users
      during their typical daily activities. Twelve individuals who used a power
      wheelchair with seating functions participated in the study. They drove their own
      wheelchair and used the seating functions as needed in their community
      environment for about 2 weeks while the seating function usage was recorded with
      a portable device. We found that subjects occupied their wheelchair for 11.8 +/-
      3.4 hours a day (all data shown as mean +/- standard deviation). While occupying
      their wheelchairs, they accessed tilt-in-space, backrest recline, and seat
      elevation 19 +/- 14 times a day for 64.1% +/- 36.8%, 12 +/- 8 times for 76.0% +/-
      29.8%, and 4 +/- 4 times for 22.5% +/- 34.9%, respectively. Subjects chose to
      stay in tilted and reclined positions in their wheelchair for 39.3% +/- 36.5% of
      their time each day. They spent little time in a fully upright position. Subjects
      changed their seating positions every 53.6 +/- 47.0 minutes. Time spent in
      positions of different seating pressures varied among subjects. The information
      collected could enhance clinical practice of wheelchair provision, resulting in
      better compliance with clinical instructions and appropriate use of seating
      functions among wheelchair users.

PMID- 19165688
TI  - Effect of rear suspension and speed on seat forces and head accelerations
      experienced by manual wheelchair riders with spinal cord injury.
AB  - Whole-body shocks and vibrations experienced during manual wheelchair use can
      decrease an individual's comfort, increase the rate of fatigue, result in injury,
      and consequently limit mobility and community participation. We used a wheelchair
      vibration simulator to examine whether the seat reaction forces experienced by
      wheelchair users were differentially influenced by wheelchair suspension, trunk
      muscle innervations, and ground speed. We used wheelchairs instrumented with load
      cells and accelerometers to determine the forces transmitted from the seat frame
      and the head accelerations experienced by riders. We determined that self
      selected speed, seat force, and head accelerations differed between subjects with
      and without trunk-muscle innervations and between rigid and suspension
      wheelchairs. Seat force and head accelerations were greatest in the rigid-frame
      wheelchair and lowest in the spring-type suspension-frame wheelchairs. Those
      participants without trunk-muscle innervations preferred slower speeds than those
      with trunk-muscle innervations. Forward head accelerations were greater in those
      without than with trunk-muscle innervations. Wheelchair rear-suspension systems
      may improve wheelchair mobility function in terms of comfort at higher velocity
      by minimizing the seat forces and head accelerations experienced by the riders,
      especially those with higher level spinal cord injury and diminished postural
      control.

PMID- 19165689
TI  - Feasibility of combining gait robot and multichannel functional electrical
      stimulation with intramuscular electrodes.
AB  - After stroke rehabilitation, many survivors of stroke exhibit persistent gait
      deficits. In previous work, we demonstrated significant gains in gait kinematics
      for survivors of chronic stroke using multichannel functional electrical
      stimulation with intramuscular electrodes (FES-IM). For this study, we tested the
      feasibility of combining FES-IM and gait robot technologies for treating
      persistent gait deficits after stroke. Six subjects, >or= 6 months after stroke,
      received 30-minute intervention sessions of combined FES-IM and gait robotics 4
      days a week for 12 weeks. Feasibility was assessed according to three factors:
      (1) performance of the interface of the two technologies during intervention
      sessions, (2) clinicians' success in using two technologies simultaneously, and
      (3) subject satisfaction. FES-IM system hardware and software design features
      combined with the gait robot technology proved feasible to use. Each technology
      alone provided unique advantages and disadvantages of gait practice
      characteristics. Because of the unique advantages and disadvantages of each
      technology, gait deficits need to be accurately identified and a judicious
      treatment plan properly targeted before FES-IM, a gait robot, or both combined
      are selected.

PMID- 19165690
TI  - Selection of optimal muscle set for 16-channel standing neuroprosthesis.
AB  - The Case Western Reserve University/Department of Veterans Affairs 8-channel
      lower-limb neuroprosthesis can restore standing to selected individuals with
      paraplegia by application of functional electrical stimulation. The second
      generation of this system will include 16 channels of stimulation and a closed
      loop control scheme to provide automatic postural corrections. This study used a
      musculoskeletal model of the legs and trunk to determine which muscles to target
      with the new system in order to maximize the range of postures that can be
      statically maintained, which should increase the system's ability to provide
      adequate support to maintain standing when the user's posture moves away from a
      neutral stance, either by an external disturbance or a volitional change in
      posture by the user. The results show that the prime muscle targets should be the
      medial gastrocnemius, tibialis anterior, vastus lateralis, semimembranosus,
      gluteus maximus, gluteus medius, adductor magnus, and erector spinae. This set of
      16 muscles supports 42% of the standing postures that are attainable by the
      nondisabled model. Coactivation of the lateral gastrocnemius and peroneus longus
      with the medial gastrocnemius and of the peroneus tertius with the tibialis
      anterior increased the percentage of feasible postures to 71%.

PMID- 19165691
TI  - Prevention of secondary stroke in VA: role of occupational therapists and
      physical therapists.
AB  - Occupational therapists (OTs) and physical therapists (PTs) have the opportunity
      and obligation to advocate secondary stroke prevention via health promotion (HP)
      behaviors. This prospective survey of Department of Veterans Affairs (VA) OTs and
      PTs determined whether they know about VA stroke rehabilitation guidelines and
      whether they integrate secondary stroke prevention into poststroke rehabilitation
      care. Questions revolved around knowledge of VA guidelines, inclusion of stroke
      risk-factor modification, and HP education to patients. Thirty-four surveys (45%)
      were returned from six facilities. Participants included 12 OTs and 22 PTs. Half
      (53%) of the therapists were aware of the VA guidelines and nearly half (48%)
      provided HP activities to patients; PTs were significantly more likely to do so
      than OTs (p = 0.02). Half of the queried therapists were unaware of the VA
      guidelines; increasing therapists' education about the guidelines and the
      necessity of HP and secondary stroke prevention may reduce veterans' risk of a
      second stroke. Because many stroke risk factors are modifiable and stroke
      survivors spend a great deal of time with the rehabilitation therapist, OTs and
      PTs can and should provide such education to reduce the risk of a second stroke.

PMID- 19165692
TI  - Geographic variation in poststroke depression among veterans with acute stroke.
AB  - This study compared patterns of poststroke depression (PSD) detection among
      veterans with acute stroke in eight U.S. geographic regions. Department of
      Veterans Affairs (VA) medical and pharmacy data as well as Medicare data were
      used. International Classification of Diseases-9th Revision depression codes and
      antidepressant medication dispensing were applied to define patients' PSD status
      12 months poststroke. Logistic regression models were fit to compare VA PSD
      diagnosis and overall PSD detection between the regions. The use of VA medical
      data alone may underestimate the rate of PSD. Geographic variation in PSD
      detection depended on the data used. If VA medical data alone were used, we found
      no significant variation. If VA medical data were used along with Medicare and VA
      pharmacy data, we observed a significant variation in overall PSD detection
      across the regions after adjusting for potential risk factors. VA clinicians and
      policy makers need to consider enrollees' use of services outside the system when
      conducting program evaluation. Future research on PSD among veteran patients
      should use VA medical data in combination with Medicare and VA pharmacy data to
      obtain a comprehensive understanding of patients' PSD.

PMID- 19165693
TI  - Content validity of a home-based person-environment interaction assessment tool
      for visually impaired adults.
AB  - Home-based assessments require in-depth analyses of daily living difficulties. No
      assessment tool that has been validated with visually impaired adult subjects has
      allowed such analysis. This research adapted a home-based person-environment
      interaction assessment tool designed for persons who are visually impaired. The
      Model of Competence, an explanatory model of the person-environment relationship,
      served as the conceptual framework. A qualitative study was conducted with
      professionals, visually impaired persons, and informal caregivers. Focus groups
      and semistructured individual interviews were used for data collection. The
      content and form had to be modified to adapt the assessment tool for use with
      visually impaired adults. This qualitative study documents the content validity
      of the Home Assessment of Person-Environment Interaction-Visual Version. The
      assessment tool will provide vision rehabilitation professionals better screens
      and explanations of handicap-created situations faced by visually impaired
      persons at home. By using a structured analysis based on a person-environment
      theoretical model, this new assessment tool fills a scientific and clinical gap,
      optimizes the evaluation process, and documents the intervention plan by
      providing an understanding of the home context.

PMID- 19165694
TI  - Lipoic acid and 6-formylpterin reduce potentiation of noise-induced hearing loss
      by carbon monoxide: preliminary investigation.
AB  - Potentiation of noise-induced hearing loss (NIHL) by specific chemical
      contaminants and therapeutic drugs represents a distinct public health risk.
      Prediction of chemicals that yield such potentiation has not been successful
      because such agents differ markedly in structure. One mechanism for this
      potentiation that has garnered support is oxidative injury to the cochlea. Thus
      far, limited data have been published in support of this hypothesis. The current
      experiment was designed to further test this model using two antioxidant
      compounds, lipoic acid (LA) and 6-formylpterin (6-FP), and determine whether they
      would block potentiation of NIHL resulting from simultaneous exposures to carbon
      monoxide (CO) and noise in rats. Neither CO nor noise exposure at the intensity
      and duration selected produce persistent auditory impairment by themselves.
      Different groups of rats were exposed to noise alone centered at 8.0 kHz (105 dB)
      for 2 hours or to combined CO + noise treatment consisting of CO exposure for 1.5
      hours and then exposure to CO + noise for 2 hours. Additional groups received
      either LA (100 mg/kg) or 6-FP (14 mg/kg) 30 minutes prior to the onset of CO +
      noise. Cochlear function was monitored using distortion product otoacoustic
      emissions, and auditory thresholds were assessed using compound action potentials
      recorded from the round window. Histopathological evaluation of the organ of
      Corti provided counts of missing hair cells in each treatment group. The CO +
      noise-exposure group replicated previous studies in demonstrating permanent
      impairment of cochlear function and associated outer hair cell loss that greatly
      exceeded the minimal losses observed in the group treated with noise alone. Both
      LA and 6-FP given 30 minutes prior to the onset of CO + noise exposure reduced
      cochlear impairment and loss of hair cells.

PMID- 19165695
TI  - Validation of FIM-MDS crosswalk conversion algorithm.
AB  - In this study, we performed a validation analysis of a crosswalk that converts
      Functional Independence Measure (FIM) scores to Minimum Data Set (MDS) scores and
      vice versa in order to achieve score compatibility. Data from 2,130 patients were
      obtained from the Department of Veteran Affairs' Austin Automation Center. The
      conversion algorithm was tested at the (1) individual patient level, (2)
      classification level, and (3) facility level. The validity testing resulted in
      mixed findings. The mean MDS-derived FIM (FIMc) scores were within 1.3 and 0.1
      points of the mean actual FIM (FIMa) scores for the motor and cognition scales,
      respectively. Kappa statistics demonstrated a fair to substantial (0.37-0.66)
      strength of agreement between functional-related group classifications generated
      from the FIMa and FIMc scores. Four of the five facilities had an average point
      difference of 2.4 between the mean FIMa and FIMc scores. While the sample
      distributions were similar, individual score comparisons fell short of
      expectations. Only 37% to 67% of the FIMc scores were within 5 points of the FIMa
      scores. The crosswalk algorithm demonstrated a convenient way to achieve score
      comparisons across different rehabilitation settings. However, the effectiveness
      of a single measure or of crosswalk conversions may ultimately depend on the
      quality of the data.

PMID- 19165696
TI  - How humans walk: bout duration, steps per bout, and rest duration.
AB  - Much is known about human walking, but it is not known how walking is used during
      typical activities. Since improving walking ability is a key goal in many
      surgical, pharmacological, and physiotherapeutic interventions, understanding
      typical community mobility demands regarding the length of walking bouts, the
      number of sequential steps frequently performed, and the duration of common
      nonwalking (rest) behavior seems prudent. This study documents the gait of daily
      living in 10 nondisabled employed adults to define walking bout duration,
      sequential step counts, and length of rest periods over a 2-week period. Subjects
      wore a StepWatch Activity Monitor (OrthoCare Innovations; Mountlake Terrace,
      Washington) that counted steps in each 10-second time window. Custom code summed
      sequential steps, periods of walking behavior (bouts), and periods without steps
      (rest). Sixty percent of all walking bouts lasted just 30 seconds or less; a 2
      minute walking bout was just 1 percent of total walking bouts. Forty percent of
      all walking bouts were less than 12 steps in a row, and 75 percent of all walking
      bouts were less than 40 steps in a row. Rest periods were predominantly very
      short, with half of all rests periods lasting 20 seconds or less. The community
      mobility demand for nondisabled employed adults appears to involve frequent short
      duration walking behavior with low numbers of sequential steps strung together
      and many short-duration nonwalking (rest) behaviors.

PMID- 19165697
TI  - Effects of acute leg ischemia during cycling on oxygen and carbon dioxide stores.
AB  - This study estimated changes in whole body oxygen stores (O(2)s) and carbon
      dioxide stores (CO(2)s) during steady state exercise with leg ischemia induced by
      leg cuff inflation. Six physically fit subjects performed 75 W steady state
      exercise for 15 min on a cycle ergometer. After 5 min of exercise, cuffs on the
      upper and lower legs were inflated to 140 mmHg. Cuffs were deflated after 5 min
      and exercise continued for another 5 min. O(2 )uptake (VO(2)) and CO(2) output
      (VCO(2)) significantly increased during the first 30 s after inflation,
      significantly decreased between 60 and 90 s, and then rose linearly until
      deflation. VO(2) and VCO(2) significantly increased further after cuff deflation,
      peaking between 30 and 60 s and then returned to near baseline exercise levels.
      Model-estimated changes in total O(2)s and CO(2)s were compared with time
      integrated store changes from VO(2) and VCO(2). During 5 min after cuff
      deflation, VO(2) and VCO(2) exceeded the model-estimated change in stores by 273
      and 697 mL, respectively. These results reflect the O(2) cost repayment of the
      anaerobic component and lactate buffering to neutralize circulating metabolites
      caused by the preceding ischemia.

PMID- 19165698
TI  - [Mould fungus--hidden in the lungs].

PMID- 19165699
TI  - [COPD--two early treatments that should be immediately followed].

PMID- 19165700
TI  - [Bronchial asthma--exacerbated by viral infections in children].

PMID- 19165702
TI  - [Allergology--horse allergens].

PMID- 19165701
TI  - [Bronchial asthma--clarithromycin depresses neutrophil inflammation].

PMID- 19165703
TI  - [Guidelines for bronchial asthma--no reference standard for small children].

PMID- 19165704
TI  - [Non-small cell bronchial carcinoma--improved detection of lymph node
      metastasis].

PMID- 19165705
TI  - Siallorrhea in pediatric neurology - the long way from case series to clinical
      studies.

PMID- 19165706
TI  - Pediatric intramedullary teratomas.
AB  - Teratomas account for 3% of all childhood tumors, with the majority occurring in
      the sacrococcygeal region and in the ovary. Intradural spinal teratomas are
      extremely rare dysembryogenetic tumors. Spinal cord teratomas may be extradural,
      intradural or intramedullary. Intramedullary ones are the least frequently seen.
      We have extensively reviewed the literature for intramedullary spinal cord
      teratomas in children. Although an intramedullary teratoma of the conus
      medullaris in children is a rare entity, it should be considered in the
      differential diagnosis of masses involving the conus medullaris.

PMID- 19165707
TI  - Successful treatment of drooling in children with neurological disorders with
      botulinum toxin A or B.
AB  - Drooling is a common and severe problem in children with neurological disorders
      and is caused by a disturbed coordination of orofacial and palatolingual muscles.
      Botulinum toxin could be a successful option to reduce excessive sialorrhea in
      children with neurological disorders. In 30 children with cerebral palsy or
      neurodegenerative disorder we injected under ultrasound guidance either botulinum
      toxin A or botulinum toxin B into the parotid and submandibular glands on both
      sides. All injections were well tolerated without general anaesthesia. Drooling
      severity at baseline and reduction of sialorrhea during treatment was measured
      using a parent's questionnaire and rated using the Teachers Drooling Scale (TDS).
      Reduction of sialorrhea was achieved two weeks after injection, with a positive
      effect lasting about three to four months in most children. 83% showed a good
      response to botulinum toxin after first injection, but only in 50% treatment was
      continued. We found no significant differences between botulinum toxin A or B.
      Side effects were observed in 5 children with viscous saliva and in one child a
      unilateral parotitis was observed. Treatment of drooling with botulinum toxin
      into the salivary glands is a safe and easy therapeutic option for children with
      neurological disorders to improve life quality.

PMID- 19165708
TI  - Gross motor profile in rett syndrome as determined by video analysis.
AB  - Movement impairment is a fundamental but variable component of the Rett syndrome
      phenotype. This study used video supplemented by parent report data to describe
      the gross motor profile in females with Rett syndrome (n=99) and to investigate
      the impact of age, genotype, scoliosis and hand stereotypies. Factor analysis
      enabled the calculation of general and complex gross motor skills scores. Most
      subjects were able to sit, slightly less than half were able to walk and a
      minority were able to transfer without assistance. General gross motor skills
      declined with age and were poorer in those who had surgically treated scoliosis
      but not conservatively managed scoliosis. Complex gross motor skills did not
      decline with age and were better in those without scoliosis. Those with a
      p.R133C, p.R294X, or a p.R255X mutation appear to have better motor skills
      overall than those with a p.R270X or large deletion mutation. Motor scores were
      not related to the frequency of hand stereotypies. This information is useful for
      the clinician and family when planning support strategies and interventions.

PMID- 19165710
TI  - Age and sex differences in brain gene expression in neonatal rats.
AB  - Gene expression in the central nervous system is highly region-specific. We
      tested the hypothesis that certain developmental biomarkers could be detected in
      the whole brain or in cortical, subcortical or cerebellar structures. Brain gene
      expressions of male and female rats at birth, 3 days, and 10 days of age were
      measured by microarray technique ( approximately 10 K genes; n=9/category). We
      found 53 significantly up-regulated and 8 down-regulated genes at 10 days of age,
      relative to birth and 3 days of age. The whole brain, however, showed no
      significant sex differences in gene expression patterns up to 10 days of age. Ten
      genes with the highest up-regulation, and 5 down-regulated genes were further
      confirmed by quantitative real-time PCR (Q-PCR), using the whole brain, cortices,
      subcortical structures, and cerebellum. The Q-PCR confirmed genes are known to be
      involved in neuronal differentiation, axonal myelination and growth,
      neurotransmission and glycolytic pathways. With a few exceptions, the expression
      levels of Q-PCR confirmed genes were significantly different in the whole brain,
      compared to other regions. In a separate study, we tested the potential utility
      of the Q-PCR confirmed genes, as whole brain biomarkers, after a six-hour
      exposure to hyperoxia (>98% oxygen breathing) in 10 days old rats. This
      relatively mild oxidative challenge created a 3.5-fold increase in the expression
      of T-cell receptor beta Variable 8.3b, known to have regulatory function during
      development. We suggest that genes displaying significant expression in the whole
      brain, regardless of their origin, could be used to screen normal brain
      development in neonatal rat models of experimental neurology.

PMID- 19165709
TI  - ABC transporter (P-gp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing
      human CNS.
AB  - P-glycoprotein (P-gp/ABCB1), multidrug resistance associated protein 1
      (MRP1/ABCC1), and breast cancer resistance protein (BCRP/ABCG2) are plasma
      membrane efflux pumps that limit the intracellular uptake and retention of
      numerous lipophilic, amphipathic xeno- and endobiotics. Little is known about the
      neonatal and developmental expression of P-gp/ABCB1, MRP1/ABCC1, and BCRP/ABCG2
      in the human central nervous system (CNS), therefore post-mortem CNS tissue from
      infants born at 22 (0/7)-42 (0/7) weeks of gestation and adults was immunostained
      to determine their ontogeny and cellular localization. P-gp/ABCB1 immunostaining
      was observed in microvessel endothelial cells as early as 22 (0/7) weeks,
      increasing in prevalence and intensity with maturation, and later in gestation in
      large pyramidal neurons. MRP1/ABCC1 immunostaining was prominent early in the
      choroid plexus and ventricular ependyma, and noted later in large pyramidal
      neurons. BCRP/ABCG2 expression was limited to microvessel endothelial cells. P
      gp/ABCB1, MRP1/ABCC1 and BCRP/ABCG2 in adult brain matched term newborn CNS but
      with more intense immunostaining. We conclude that P-gp/ABCB1, MRP1/ABCC1, and
      BCRP/ABCG2 are expressed in a developmental, cell specific, fashion in the human
      CNS. The complementary pattern of P-gp/ABCB1 and BCRP/ABCG2 at the blood-brain
      with MRP1/ABCC1 at the blood-CSF barriers may limit CNS uptake and retention of
      drugs and toxins in neonates.

PMID- 19165711
TI  - Electroencephalogram and flash visual evoked potentials for detecting
      periventricular leukomalacia.
AB  - OBJECTIVE: The aim of this study was to evaluate the usefulness of a combination
      of electroencephalogram (EEG) and flash visual evoked potentials (FVEPs) for
      predicting periventricular leukomalacia (PVL) in the early days of life. STUDY
      DESIGN: Eighty-six of 108 infants admitted to Anjo Kosei Hospital during 1998
      through 2000 were enrolled in this study. All subjects underwent EEG and FVEP
      during the early neonatal period and were followed-up until 18 months of
      corrected age. EEG was performed once within 72 h after birth, every 1-2 weeks
      during the first month and every 2-4 weeks during the second month. FVEPs were
      recorded at least twice, at the first and the second week of life. RESULTS: Of
      the 86 infants, 13 were diagnosed as having PVL. Among them, EEG abnormalities
      were observed in 11 infants and FVEP abnormalities in 10. The sensitivity and
      specificity of EEG were 0.85 and 0.95, respectively. The sensitivity and
      specificity of FVEPs were 0.77 and 0.96, respectively. All except one (92%)
      infant with PVL had EEG and/or FVEP abnormalities. CONCLUSIONS: The combination
      of EEG and FVEPs can increase the sensitivity, but reduces the specificity to
      identify infants with PVL. The combination can makes up for the shortcomings of
      each method.

PMID- 19165712
TI  - Diffusion-weighted magnetic resonance imaging in infants with periventricular
      leukomalacia.
AB  - OBJECTIVE: We examined diffusion-weighted magnetic resonance imaging (DWI)
      findings in periventricular leukomalacia (PVL) and then evaluated the
      relationship between the mean apparent diffusion coefficient (ADC) values and the
      region and severity of PVL. METHODS: Between April 2006 and July 2007, 98 infants
      at gestational ages between 27 and 33 weeks were enrolled in the study. DWI was
      performed during the first week of life when electroencephalography indicated
      PVL. The mean ADC values were evaluated using regions of interest drawn manually
      in the periventricular white matter, posterior limbs of internal capsules
      (PLICs), and various regions of the brain. RESULTS: DWI was performed in three of
      four infants with PVL indicated on electroencephalography. All had decreased
      diffusivity in the anterior to posterior white matter despite a predominance in
      the posterior white matter. DWI abnormalities were also observed in the corpus
      callosum and PLICs and were more broadly distributed in the brain than those
      detected by later conventional MRI. In the PLICs, the changes in the ADC values
      were correlated with the severity of the PVL. CONCLUSION: The DWI findings
      provided additional information regarding PVL. Among the findings, the
      association of the presence of decreased diffusivity in the corticospinal tract
      with later motor impairment was the most interesting.

PMID- 19165713
TI  - Return to participation - significant improvement after bilateral pallidal
      stimulation in rapidly progressive DYT-1 dystonia.
AB  - We report the case of an 8-year-old girl who developed progressive generalized
      dystonia, rendering her unable to walk and sit within months despite medical
      therapy with dopamine and anti-cholinergic agents. She was found to have a 9q34.1
      GAG-deletion, which is known to cause DYT1-dystonia. DYT-1 dystonia is an
      autosomal dominant condition with incomplete penetrance that usually starts in
      childhood. It is known to be refractory to pharmacotherapy. Reports on deep brain
      stimulation in this condition reveal marked benefits of the treatment in the
      pediatric and adult populations. The patient underwent bilateral stimulation of
      the internal globus pallidus 18 months after symptom onset. Postoperatively, her
      clinical status improved significantly as measured by the Burke-Fahn-Marsden
      dystonia rating scale and the resolution of a unilateral hip dislocation. Normal
      participation was regained.

PMID- 19165714
TI  - Pilomyxoid astrocytoma of the spinal cord with cerebrospinal fluid and peritoneal
      metastasis.
AB  - Pilomyxoid astrocytoma (PMA) is a recently described rare tumor which is a
      variant of pilocytic astrocytoma (PA). It exhibits a more aggressive behavior
      than PA. Spinal cord PMA has been reported in two articles in the past and none
      of the reported case had extraneural metastasis. We report on a female child with
      cervical cord PMA with diffuse leptomeningeal metastasis involving the brain and
      spinal cord. Two years later she presented with peritoneal carcinomatoses which
      was consistent with metastatic tumor via a ventriculoperitoneal (VP) shunt. This
      case confirms the aggressive behavior of PMA and makes clinicians aware of the
      possibility of extraneural, peritoneal metastasis through a VP shunt.

PMID- 19165715
TI  - Regulatory role of ginsenoside Rp1, a novel ginsenoside derivative, on CD29
      mediated cell adhesion.
AB  - In this study, we examined the regulatory role of G-Rp1 on cell adhesion events
      mediated by beta1-integrins (CD29). Using a U937 cell-cell adhesion assay, we
      found that exogenous G-Rp1 down-regulates CD29 activation in a dose-dependent
      manner, whereas G-Rg3 did not cause the same effect. However, G-Rp1 increased
      cell-fibronectin adhesion comparable to cytochalasin B, an actin cytoskeleton
      disruptor. Furthermore, G-Rp1 also blocked the rearrangement of actin at sites of
      cell-cell contact, indicating that the actin cytoskeleton may be a target of G
      Rp1 action. Interestingly, G-Rp1 suppressed dephosphorylation of vasodilator
      stimulated phosphoprotein (VASP) at Ser-157, known to be an actin cytoskeleton
      modulatory protein. These results suggest that G-Rp1 may act as a novel regulator
      of CD29-mediated cell adhesion events, which are involved in numerous
      pathological symptoms.

PMID- 19165716
TI  - Near infrared spectroscopy in natural products analysis.
AB  - Several medicinal and herbal plants properties are related to individual
      compounds such as essential oils, terpenoids, flavonoids, which are present in
      natural products in low concentrations (e. g., ppm or ppb). For many years, the
      use of classical separation and chromatographic and spectrometric techniques such
      as high performance liquid chromatography (HPLC), gas chromatography (GC), liquid
      chromatography (LC) and mass spectrometry (MS) were initially used for the
      elucidation of isolated compounds from different plant matrices. Spectroscopic
      techniques in the infrared (IR) wavelength region of the electromagnetic spectrum
      have been used in the food industry to monitor and evaluate the composition of
      foods. Although Herschel discovered light in the near-infrared (NIR) region as
      early as 1800, most spectroscopists of the first half of the last century ignored
      it, in the belief that it lacked any analytical interest. However, during the
      last 40 years NIR spectroscopy has become one of the most attractive and used
      methods for analysis. This mini-review highlights recent applications of NIR
      spectroscopy to the qualitative and quantitative analysis of plant natural
      products.

PMID- 19165717
TI  - [Recent job description of the honorary physician--a need will become a virtue].

PMID- 19165719
TI  - Residual structure within the disordered C-terminal segment of
      p21(Waf1/Cip1/Sdi1) and its implications for molecular recognition.
AB  - Probably the most unusual class of proteins in nature is the intrinsically
      unstructured proteins (IUPs), because they are not structured yet play essential
      roles in protein-protein signaling. Many IUPs can bind different proteins, and in
      many cases, adopt different bound conformations. The p21 protein is a small IUP
      (164 residues) that is ubiquitous in cellular signaling, for example, cell cycle
      control, apoptosis, transcription, differentiation, and so forth; it binds to
      approximately 25 targets. How does this small, unstructured protein recognize
      each of these targets with high affinity? Here, we characterize residual
      structural elements of the C-terminal segment of p21 encompassing residues 145
      164 using a combination of NMR measurements and molecular dynamics simulations.
      The N-terminal half of the peptide has a significant helical propensity which is
      recognized by calmodulin while the C-terminal half of the peptide prefers
      extended conformations that facilitate binding to the proliferating cell nuclear
      antigen (PCNA). Our results suggest that the final bound conformations of p21
      (145-164) pre-exist in the free peptide even without its binding partners. While
      the conformational flexibility of the p21 peptide is essential for adapting to
      diverse binding environments, the intrinsic structural preferences of the free
      peptide enable promiscuous yet high affinity binding to a diverse array of
      molecular targets.

PMID- 19165720
TI  - An approach to characterizing single-subunit mutations in multimeric prepores and
      pores of anthrax protective antigen.
AB  - Heptameric pores formed by the protective antigen (PA) moiety of anthrax toxin
      translocate the intracellular effector moieties of the toxin across the endosomal
      membrane to the cytosol of mammalian cells. We devised a protocol to characterize
      the effects of individual mutations in a single subunit of heptameric PA prepores
      (pore precursors) or pores. We prepared monomeric PA containing a test mutation
      plus an innocuous Cys-replacement mutation at a second residue (Lys563, located
      on the external surface of the prepore). The introduced Cys was biotinylated, and
      the protein was allowed to cooligomerize with a 20-fold excess of wild-type PA.
      Finally, biotinylated prepores were freed from wild-type prepores by avidin
      affinity chromatography. For the proof of principle, we examined single-subunit
      mutations of Asp425 and Phe427, two residues where Ala replacements have been
      shown to cause strong inhibitory effects. The single-subunit D425A mutation
      inhibited pore formation by >10(4) and abrogated activity of PA almost completely
      in our standard cytotoxicity assay. The single-subunit F427A mutation caused
      approximately 100-fold inhibition in the cytotoxicity assay, and this effect was
      shown to result from a combination of strong inhibition of translocation and
      smaller effects on pore formation and ligand affinity. Our results show
      definitively that replacing a single residue in one subunit of the heptameric PA
      prepore can inhibit the transport activity of the oligomer almost completely-and
      by different mechanisms, depending on the specific residue mutated.

PMID- 19165721
TI  - Genetic selection system for improving recombinant membrane protein expression in
      E. coli.
AB  - A major barrier to the physical characterization and structure determination of
      membrane proteins is low yield in recombinant expression. To address this
      problem, we have designed a selection strategy to isolate mutant strains of
      Escherichia coli that improve the expression of a targeted membrane protein. In
      this method, the coding sequence of the membrane protein of interest is fused to
      a C-terminal selectable marker, so that the production of the selectable marker
      and survival on selective media is linked to expression of the targeted membrane
      protein. Thus, mutant strains with improved expression properties can be directly
      selected. We also introduce a rapid method for curing isolated strains of the
      plasmids used during the selection process, in which the plasmids are removed by
      in vivo digestion with the homing endonuclease I-CreI. We tested this selection
      system on a rhomboid family protein from Mycobacterium tuberculosis (Rv1337) and
      were able to isolate mutants, which we call EXP strains, with up to 75-fold
      increased expression. The EXP strains also improve the expression of other
      membrane proteins that were not the target of selection, in one case roughly 90
      fold.

PMID- 19165722
TI  - Random dissection to select for protein split sites and its application in
      protein fragment complementation.
AB  - To identify protein split sites quickly, a selection procedure by using
      chloramphenicol acetyl transferase (CAT) as reporter was introduced to search for
      folded protein fragments from libraries generated by random digestion and
      reassembly of the target gene, which yielded an abundant amount of DNA fragments
      with controllable lengths. Experimental results of tryptophan synthase alpha
      subunit (TSalpha) and TEM-1 beta-lactamase agreed well with what the literature
      has reported. The solubility of these fragments correlated roughly with the
      minimum inhibitory concentrations of the CAT fusions. The application of this
      dissection protocol to protein fragment complementation assay (PCA) was evaluated
      using aminoglycoside-3'-phosphotransferase I (APH(3')-I) as a model protein.
      Three nearly bisectional sites and a number of possible split points were
      identified, and guided by this result, four novel pairs of fragments were tested
      for complementation. Three out of four pairs partially restored the APH activity
      with the help of leucine zippers, and a truncated but active APH(3')-I (Delta1
      25) was also found. Finally, the weakly active APH(3')-I-(1-253)NZ/CZ (254-271)
      containing a short 18 residue tag was further improved by error-prone PCR, and a
      best mutant was obtained showing a fourfold improvement after just one round of
      evolution. These results demonstrate that protein random dissection based on the
      CAT selection can provide an efficient search for protein breakage points and
      guide the design of fragments for protein complementation assay. Furthermore,
      more active fragment pairs can be achieved with the classical directed evolution
      approach.

PMID- 19165723
TI  - Methionine oxidation in human IgG2 Fc decreases binding affinities to protein A
      and FcRn.
AB  - Susceptibility of methionine residues to oxidation is a significant issue of
      protein therapeutics. Methionine oxidation may limit the product's clinical
      efficacy or stability. We have studied kinetics of methionine oxidation in the Fc
      portion of the human IgG2 and its impact on the interaction with FcRn and Protein
      A. Our results confirm previously published observations for IgG1 that two
      analogous solvent-exposed methionine residues in IgG2, Met 252 and Met 428,
      oxidize more readily than the other methionine residue, Met 358, which is buried
      inside the Fc. Met 397, which is not present in IgG1 but in IgG2, oxidizes at
      similar rate as Met 358. Oxidation of two labile methionines, Met 252 and Met
      428, weakens the binding of the intact antibody with Protein A and FcRn, two
      natural protein binding partners. Both of these binding partners share the same
      binding site on the Fc. Additionally, our results shows that Protein A may serve
      as a convenient and inexpensive surrogate for FcRn binding measurements.

PMID- 19165724
TI  - Re-engineering a beta-lactamase using prototype peptides from a library of local
      structural motifs.
AB  - B. licheniformis exo-small beta-lactamase (ESBL) has a complex architecture with
      twelve alpha helices and a five-stranded beta sheet. We replaced, separately or
      simultaneously, three of the ESBL alpha helices with prototype amphiphatic
      helices from a catalog of secondary structure elements. Although the substitutes
      bear no sequence similarity to the originals and pertain to unrelated protein
      families, all the engineered ESBL variants were found able to fold in native like
      structures with in vitro and in vivo enzymic activity. The triple substituted
      variant resembles a primitive protein, with folding defects such as a strong
      tendency to oligomerization and very low stability; however it mimics a non
      homologous recombinant abandoning the family sequence space while preserving
      fold. The results test protein folding and evolution theories.

PMID- 19165725
TI  - Atomic resolution structure of the cytoplasmic domain of Yersinia pestis YscU, a
      regulatory switch involved in type III secretion.
AB  - Crystal structures of cleaved and uncleaved forms of the YscU cytoplasmic domain,
      an essential component of the type III secretion system (T3SS) in Yersinia
      pestis, have been solved by single-wavelength anomolous dispersion and refined
      with X-ray diffraction data extending up to atomic resolution (1.13 A). These
      crystallographic studies provide structural insights into the conformational
      changes induced upon auto-cleavage of the cytoplasmic domain of YscU. The
      structures indicate that the cleaved fragments remain bound to each other. The
      conserved NPTH sequence that contains the site of the N263-P264 peptide bond
      cleavage is found on a beta-turn which, upon cleavage, undergoes a major
      reorientation of the loop away from the catalytic N263, resulting in altered
      electrostatic surface features at the site of cleavage. Additionally, a
      significant conformational change was observed in the N-terminal linker regions
      of the cleaved and noncleaved forms of YscU which may correspond to the molecular
      switch that influences substrate specificity. The YscU structures determined here
      also are in good agreement with the auto-cleavage mechanism described for the
      flagellar homolog FlhB and E. coli EscU.

PMID- 19165726
TI  - The strong dimerization of the transmembrane domain of the fibroblast growth
      factor receptor (FGFR) is modulated by C-terminal juxtamembrane residues.
AB  - The fibroblast growth factor receptor 3 (FGFR3) is a member of the FGFR subfamily
      of the receptor tyrosine kinases (RTKs) involved in signaling across the plasma
      membrane. Generally, ligand binding leads to receptor dimerization and
      activation. Dimerization involves the transmembrane (TM) domain, where mutations
      can lead to constitutive activation in certain cancer types and also in skeletal
      malformations. Thus, it has been postulated that FGFR homodimerization must be
      inherently weak to allow regulation, a feature reminiscent of alpha and beta
      integrin TM interactions. However, we show herein that in FGFR3-TM, four C
      terminal residues, CRLR, have a profound destabilizing effect in an otherwise
      strongly dimerizing TM peptide. In the absence of these four residues, the
      dimerizing propensity of FGFR3-TM is comparable to glycophorin, as shown using
      various detergents. In addition, the expected enhanced dimerization induced by
      the mutation associated to the Crouzon syndrome A391E, was observed only when
      these four C-terminal residues were present. In the absence of these four
      residues, A391E was dimer-destabilizing. Finally, using site specific infrared
      dichroism and convergence with evolutionary conservation data, we have determined
      the backbone model of the FGFR3-TM homodimer in model lipid bilayers. This model
      is consistent with, and correlates with the effects of, most known pathological
      mutations found in FGFR-TM.

PMID- 19165727
TI  - Unique interactions between the chromophore and glutamate 16 lead to far-red
      emission in a red fluorescent protein.
AB  - mPlum is a far-red fluorescent protein with emission maximum at approximately 650
      nm and was derived by directed evolution from DsRed. Two residues near the
      chromophore, Glu16 and Ile65, were previously revealed to be indispensable for
      the far-red emission. Ultrafast time-resolved fluorescence emission studies
      revealed a time dependent shift in the emission maximum, initially about 625 nm,
      to about 650 nm over a period of 500 ps. This observation was attributed to rapid
      reorganization of the residues solvating the chromophore within mPlum. Here, the
      crystal structure of mPlum is described and compared with those of two blue
      shifted mutants mPlum-E16Q and -I65L. The results suggest that both the identity
      and precise orientation of residue 16, which forms a unique hydrogen bond with
      the chromophore, are required for far-red emission. Both the far-red emission and
      the time dependent shift in emission maximum are proposed to result from the
      interaction between the chromophore and Glu16. Our findings suggest that
      significant red shifts might be achieved in other fluorescent proteins using the
      strategy that led to the discovery of mPlum.

PMID- 19165728
TI  - Detachment of sprayed colloidal copper oxychloride-metalaxyl fungicides by a
      shallow water flow.
AB  - BACKGROUND: Flow shear stress induced by rainfall promotes the loss of the
      pesticides sprayed on crops. Some of the factors influencing the losses of
      colloidal-size particulate fungicides are quantified by using a rotating shear
      system model. With this device it was possible to analyse the flow shear
      influencing washoff of a commercial fungicide formulation based on a copper
      oxychloride-metalaxyl mixture that was sprayed on a polypropylene surface. A
      factor plan with four variables, i.e. water speed and volume (both variables
      determining flow boundary stress in the shear device), formulation dosage and
      drying temperature, was set up to monitor colloid detachment. RESULTS: This
      experimental design, together with sorption experiments of metalaxyl on copper
      oxychloride, and the study of the dynamics of metalaxyl and copper oxychloride
      washoff, made it possible to prove that metalaxyl washoff from a polypropylene
      surface is controlled by transport in solution, whereas that of copper
      oxychloride occurs by particle detachment and transport of particles. Average
      losses for metalaxyl and copper oxychloride were, respectively, 29 and 50% of the
      quantity applied at the usual recommended dosage for crops. CONCLUSION: The key
      factors affecting losses were flow shear and the applied dosage. Empirical models
      using these factors provided good estimates of the percentage of fungicide loss.
      From the factor analysis, the main mechanism for metalaxyl loss induced by a
      shallow water flow is solubilisation, whereas copper loss is controlled by
      erosion of copper oxychloride particles.

PMID- 19165729
TI  - Resistance of Pakistani field populations of spotted bollworm Earias vittella
      (Lepidoptera: Noctuidae) to pyrethroid, organophosphorus and new chemical
      insecticides.
AB  - BACKGROUND: The spotted bollworm Earias vittella (Fab.) is a serious pest of
      cotton and okra in Pakistan. Owing to persistent use of insecticides, this pest
      has developed resistance, especially to pyrethroids. The present studies aimed at
      determining the extent of resistance to pyrethroid, organophosphorus and new
      chemical insecticides in Pakistani populations of E. vittella. RESULTS: Field
      populations of E. vittella were monitored at Multan, Pakistan, from 1999 to 2007
      for their resistance against six pyrethroid, four organophosphorus and six new
      chemical insecticides using a leaf-dip bioassay. Of the pyrethroids, resistance
      was generally low to zeta-cypermethrin and moderate to high or very high to
      cypermethrin, deltamethrin, esfenvalerate, bifenthrin and lambda-cyhalothrin.
      Resistance to organophosphates chlorpyrifos, profenofos, triazophos and phoxim
      was recorded at very low to low levels. Among new chemicals, E. vittella had no
      or a very low resistance to spinosad, emamectin benzoate and methoxyfenozide, a
      very low to low resistance to abamectin, a very low to moderate resistance to
      indoxacarb and a moderate resistance to chlorfenapyr. CONCLUSION: The results
      indicate a lack of cross-resistance between pyrethroid and organophosphorus
      insecticides in E. vittella. Rotation of insecticides showing no, very low or low
      resistance, but belonging to different insecticide classes with unrelated modes
      of action, may prevent or mitigate insecticide resistance in E. vittella.

PMID- 19165730
TI  - Formulation and application of entomopathogenic nematode-infected cadavers for
      control of Hoplia philanthus in turfgrass.
AB  - BACKGROUND: Commercially produced entomopathogenic nematodes (EPNs) are usually
      applied in an aqueous suspension. However, recent studies demonstrate that they
      can be successfully applied as infected cadavers. EPN-infected insect cadavers
      were formulated in various carrier/coating materials, but only infective
      juveniles (IJs) from kaolin-formulated and non-formulated cadavers were tested
      for survival, emergence and virulence. The efficacy of IJs from kaolin-formulated
      and non-formulated cadavers applied against Hoplia philanthus Fuessly in
      greenhouse and field was also assessed. RESULTS: The kaolin-based formulation
      (kaolin-starch combination) proved to be the most stable. Emergence of
      Heterorhabditis bacteriophora Poinar CLO51 from cadavers formulated in kaolin was
      significantly higher than from non-formulated cadavers. In greenhouse conditions,
      efficacy of freshly formulated (8 days post-infection) cadavers of H.
      bacteriophora provided significantly higher H. philanthus control (62%) than
      three-month-old cadavers (31%) or aqueous applications of the same EPN (39% and
      43%). Similarly, under field conditions, significantly higher H. philanthus
      control was achieved with freshly formulated cadavers (39%) than with three-month
      old cadavers (21%) or with aqueous applications (24% and 28%) of H. bacteriophora
      2 weeks after application. Additionally, after 1 year, cadaver applications
      provided >90% H. philanthus control, while aqueous applications of H.
      bacteriophora gave only 55% control. CONCLUSIONS: This study demonstrated that
      kaolin-starch coating provided superior protection and preservation of EPN
      infected cadavers. Use of formulated cadavers may solve several current problems
      preventing the wider utilisation of EPNs in pest management.

PMID- 19165731
TI  - Properties of experimental titanium-silver-copper alloys for dental applications.
AB  - The aim of this study was to develop Ti-Ag-Cu alloys with a higher corrosion
      resistance, better biocompatibility, and better mechanical properties than
      commercially pure titanium and its alloys. The microstructure, corrosion
      resistance, mechanical property and cytotoxicity of the Ti-Ag-Cu alloys were
      investigated. The corrosion resistance was evaluated by open circuit potential
      measurements and potentiodynamic polarization tests in artificial saliva at 37
      degrees C. The mechanical properties were evaluated using tensile and
      microhardness tests. The biocompatibility was tested by evaluating the
      cytotoxicity of the alloys using an agar-overlay test and MTT assay. It was found
      that the open circuit potentials of the Ti-Ag-Cu alloys were higher than that of
      pure Ti. However, the passive current densities of the Ti-Ag-Cu alloys were
      similar to that of pure titanium. The mechanical properties improved with
      increasing Ag and Cu content. All the Ti-Ag-Cu alloys examined were found to be
      noncytotoxic similar to pure Ti. Therefore, Ti-Ag-Cu alloys can be used as
      biomaterials in the dental field.

PMID- 19165732
TI  - Effect of spongin derived from Hymeniacidon sinapium on bone mineralization.
AB  - Marine sponges have been known to provide a source of novel bone and cartilage
      replacements because of their secondary metabolites and specific skeleton
      structures. In particular, it has been reported that spongin as a component of
      fibrous skeleton, pseudokeratin, neurokeratin, horny protein, and collagen-like
      protein in sponges can be used in several biomedical applications including
      osteoarthritis (OA). However, the pharmacological mechanism of action of spongin
      remains obscure. In this study, it was investigated whether spongin derived from
      Hymeniacidon sinapium can promote bone mineralization of osteoblast-like MG-63
      cells. Our present study provides the first evidence that spongin is effective in
      activating bone mineralization. Furthermore, spongin increased ALP activity,
      collagen synthesis, and osteocalcin secretion in addition to bone mineralization
      in osteoblastic cells in vitro. In addition, it was demonstrated that spongin
      exerted the inhibitory effect on production of inflammatory mediators such as TNF
      alpha, IL-1beta, and PGE(2) in macrophage, RAW264.7 cells. These results suggest
      that the anti-inflammatory effect of spongin derived from Hymeniacidon sinapium
      can play a critical role in bone mineralization of osteoblast-like MG-63 cells.

PMID- 19165733
TI  - In vivo response of novel calcium phosphate-mullite composites: results up to 12
      weeks of implantation.
AB  - In this paper, the in vivo response, in particular, the histocompatibility of
      newly developed CaP-mullite composites is reported. In the present experiments,
      the bioceramic implants were inserted in the long bones of healthy rabbits
      according to standard protocols (ISO-10993) and the tissue response was studied
      at different time intervals of up to 12 weeks. Ultra high-molecular weight
      polyethylene (UHMWPE) was used as control samples. The postimplant bone-material
      interfaces were analyzed by staining of histological sections, following bone
      tissue histopathology protocols. The interface zones were critically observed by
      fluorescent optical microscopy, scanning electron microscopy (SEM), and atomic
      force microscopy (AFM). Importantly, no inflammation, necrosis was observed
      during this tenure. New bone formation was observed at all the implantation time
      intervals (1-12 weeks). However, the bone integrity with the material was
      increased after 12 weeks of implantation. Although macrophages and fibrous tissue
      were present during the first week of implantation, they were not observed on
      histology sections after 12 weeks postimplantation. More importantly, foci of
      chondrocytes could be observed after 12 weeks of implantation. Remodeling of
      Haversian canal was observed at the interfacial area of natural bone and implant
      material. All the observations were assessed critically to analyze the in vivo
      biocompatibility of this novel composite material.

PMID- 19165734
TI  - In situ indentation of nanoporous gold thin films in the transmission electron
      microscope.
AB  - The mechanical behavior of nanoporous gold was investigated during in situ
      nanoindentation in the transmission electron microscope. Thin films of nanoporous
      gold, with ligaments and pores of the order of 10-nm diameter, offer a highly
      constrained geometry for deformation and thus provide an opportunity to study the
      role of defects such as dislocations in the plasticity of nanomaterials. Films
      ranging in thickness from 75 to 300 nm were indented, while the motion of
      dislocations and deformation of ligaments were observed in situ. Dislocations
      were generated and moved along ligament axes, after which they interacted with
      other dislocations in the nodes of the porous network. For thicker films, the
      load-displacement curves exhibited load drops at regular intervals. The question
      of whether the spacing of these load drops was related to the collapse of pores
      in the nanoporous films or due to bursts of plasticity within the ligaments was
      investigated. Additionally, the effect of the indenter displacement rate on the
      mechanical response of these gold films with nanoscale porosity was investigated.
      Indentation rates were varied from 1.5 to 30 nm/s. There appears to be a kinetic
      factor related to dislocation nucleation, where slower displacement rates cause
      load drops to occur at shorter distance intervals and over longer time intervals.

PMID- 19165735
TI  - Dose-dependent effects on cell proliferation, seminiferous tubules, and male germ
      cells in the fetal rat testis following exposure to di(n-butyl) phthalate.
AB  - Adult male rats gestationally exposed to di(n-butyl)phthalate (DBP) have
      dysgenetic testes characterized by seminiferous epithelial degeneration,
      clustering of Leydig cells, and decreased spermatogenesis. Cell proliferation and
      apoptosis are key processes regulating development of the testis, and alterations
      in these processes may underlie testicular dysgenesis. OBJECTIVE: To determine
      whether gestational exposure to DBP affects cell proliferation and apoptosis in
      the developing rat testis. DESIGN: Pregnant dams were exposed to different dose
      levels of DBP in mid-gestation and cellular outcomes in fetal and early postnatal
      testes were assayed by histological and morphometric approaches. RESULTS:
      Gestational exposure to high dose DBP inhibited proliferation of fetal testicular
      somatic cells but did not affect apoptosis. Exposed fetal testes had a smaller
      volume and decreased cell numbers, with decreases in both the tubular and
      interstitial cell populations. A reduction was observed in the testis volume and
      altered seminiferous tubule morphometry at > or =50 mg/kg/d, and a decreased
      testicular cell number at > or =30 mg/kg/d DBP. The number of multinucleated
      gonocytes in DBP-exposed fetal testes increased after exposure to > or =100
      mg/kg/d. The number of proliferating cells in the DBP-exposed testis rapidly rose
      after birth (when exposure stopped), and the testis volume and the total cell
      number was comparable to control by postnatal day 2. CONCLUSION: DBP reversibly
      inhibits proliferation of somatic cells in the fetal rat testis. Decreased
      proliferation, rather than increased apoptosis, is the underlying mechanism of
      altered fetal development of DBP-exposed seminiferous tubules contributing to
      testicular dysgenesis.

PMID- 19165736
TI  - The influence of chromatic components on extended depth of field imaging.
AB  - The analysis of variance is one of the most commonly used algorithms for
      detecting focalized zones in digital images and is an entry point to extended
      focalization techniques beyond those established by optical laws. This article
      analyses the dependence of the red, green, and blue (RGB) and lightness, hue, and
      saturation (LHS) components when used as the basis for applying an algorithm to
      obtain images with extended depth of field. Also, an algorithm developed by the
      authors is described and the dependence of the final result is shown according to
      the chromatic components used as the variables. Finally, a methodology is defined
      based on the study of second variance in relation to the number of images and
      pixels of the chromatic coordinates to decide which to use as the basis for the
      calculation.

PMID- 19165737
TI  - Detection of pollen grains in multifocal optical microscopy images of air
      samples.
AB  - Pollen is a major cause of allergy and monitoring pollen in the air is relevant
      for diagnostic purposes, development of pollen forecasts, and for biomedical and
      biological researches. Since counting airborne pollen is a time-consuming task
      and requires specialized personnel, an automated pollen counting system is
      desirable. In this article, we present a method for detecting pollen in
      multifocal optical microscopy images of air samples collected by a Burkard pollen
      sampler, as a first step in an automated pollen counting procedure. Both color
      and shape information was used to discriminate pollen grains from other airborne
      material in the images, such as fungal spores and dirt. A training set of 44
      images from successive focal planes (stacks) was used to train the system in
      recognizing pollen color and for optimization. The performance of the system has
      been evaluated using a separate set of 17 image stacks containing 65 pollen
      grains, of which 86% was detected. The obtained precision of 61% can still be
      increased in the next step of classifying the different pollen in such a counting
      system. These results show that the detection of pollen is feasible in images
      from a pollen sampler collecting ambient air. This first step in automated pollen
      detection may form a reliable basis for an automated pollen counting system.

PMID- 19165738
TI  - Digital titration: automated image acquisition and analysis of load and growth of
      Chlamydophila psittaci.
AB  - Traditionally, the amount of infective chlamydiae in a given sample is determined
      by inoculating dilution series into cell cultures and physically counting
      chlamydial inclusions. This approach is time consuming, tedious, and error prone,
      mainly when dealing with high titers. Therefore, this paper describes a largely
      automated technique that was developed to standardize the determination of
      chlamydial load in vitro. Cells are fixed at 36 h post-inoculation and bacteria
      visualized using standard immunological detection methods. Consequently, for 81
      microscopic fields, an image is recorded at the interpolated focal plane. These
      images are then automatically processed using an ImageJ plugin and the obtained
      results are imported into Excel to determine the number of inclusion forming
      units per mL in the sample. The main advantage of this technique is that no or
      minimal sample dilution is required, thus minimizing dilution errors. In
      addition, this technique was employed during the early, middle and late growth
      stages of the chlamydial developmental cycle and results correlated well (P <
      0.01) with 16S rRNA values from previous experiments, thereby proving its
      suitability to follow chlamydial growth in vitro. The method described is highly
      suitable for high throughput titration of cell culture inoculated samples and
      assessment of possible antichlamydial effects of novel compounds throughout the
      chlamydial growth cycle.

PMID- 19165739
TI  - Application of micro-CT: a new method for stone drilling research.
AB  - Drilling is one of the most complex techniques for making ancient stone implement
      or adornment. For smaller perforations, it is very difficult to effectively
      observe drilling marks under microscope, SEM, or to obtain negative silicone
      rubber cast. In this report, a new exclusive nondestructive method was first
      introduced to resolve the observation difficulty. Virtual 3D reconstruction by
      using micro CT (microCT) was successfully applied to disclose drilling tool marks
      on the inner wall of one small perforation and its relative drilling technique
      was deduced, which implied that microCT has great potential to understand ancient
      stone drilling.

PMID- 19165740
TI  - Laser-based in situ techniques: novel methods for generating extreme conditions
      in TEM samples.
AB  - The dynamic transmission electron microscope (DTEM) is introduced as a novel tool
      for in situ processing of materials. Examples of various types of dynamic studies
      outline the advantages and differences of laser-based heating in the DTEM in
      comparison to conventional (resistive) heating in situ TEM methods. We
      demonstrate various unique capabilities of the drive laser, namely, in situ
      processing of nanoscale materials, rapid and high temperature phase
      transformations, and controlled thermal activation of materials. These
      experiments would otherwise be impossible without the use of the DTEM drive
      laser. Thus, the potential of the DTEM as a new technique to process and
      characterize the growth of a myriad of micro and nanostructures is demonstrated.

PMID- 19165741
TI  - In situ TEM observation of magnetic materials.
AB  - Magnetic nanostructures and thin films display novel magnetization reversal
      behavior as a function of size and shape, which makes them appropriate for a
      range of technological applications. The spatial resolution of in situ
      transmission electron microscopy techniques such as Lorentz TEM (LTEM) and off
      axis electron holography are well suited to analysis of the magnetic domain
      structure and magnetization behavior of these magnetic nanostructures and thin
      films. In this article the various techniques that are applicable are described,
      including the qualitative LTEM imaging modes and the differential phase contrast
      technique. In addition, quantitative methods for mapping the magnetic induction
      via phase reconstruction are discussed. In each case the advantages and
      limitations are presented. Application of the techniques to various types of
      magnetic structures is then presented, and the article ends with a short summary
      and a discussion of future developments in this field.

PMID- 19165742
TI  - A new MEMS-based system for ultra-high-resolution imaging at elevated
      temperatures.
AB  - In recent years, an increasing number of laboratories have been applying in situ
      heating (and ultimately, gas reaction) techniques in electron microscopy studies
      of catalysts and other nanophase materials. With the advent of aberration
      corrected electron microscopes that provide sub-Angstrom image resolution, it is
      of great interest to study the behavior of materials at elevated temperatures
      while maintaining the resolution capabilities of the microscope. In collaboration
      with Protochips Inc., our laboratory is developing an advanced capability for in
      situ heating experiments that overcomes a number of performance problems with
      standard heating stage technologies. The new heater device allows, for example,
      temperature cycling from room temperature to greater than 1000 degrees C in 1 ms
      (a heating rate of 1 million Centigrade degrees per second) and cooling at nearly
      the same rate. It also exhibits a return to stable operation (drift controlled by
      the microscope stage, not the heater) in a few seconds after large temperature
      excursions. With Protochips technology, we were able to demonstrate single atom
      imaging and the behavior of nanocrystals at high temperatures, using high-angle
      annular dark-field imaging in an aberration-corrected (S)TEM. The new capability
      has direct applicability for remote operation and (ultimately) for gas reaction
      experiments using a specially designed environmental cell.

PMID- 19165743
TI  - New rabbit knee model of posttraumatic joint contracture: indirect capsular
      damage induces a severe contracture.
AB  - Reported models of joint contracture fail to result in severe motion loss. Our
      purpose was to develop a rabbit model of knee contracture and compare it to
      another well-accepted model to determine if more severe stiffness can be
      achieved. Sixteen skeletally mature New Zealand White female rabbits had their
      right knee operated to create 3-mm defects on the noncartilaginous portions of
      the femoral condyles, hyperextend the joint to disrupt the posterior capsule, and
      immobilize the joint in maximum flexion with a Kirschner-wire for 8 weeks (group
      I). Sixteen additional rabbits were operated on using an identical protocol
      except for the absence of capsular injury (group II). In each group, mechanical
      testing was performed at the time of Kirschner-wire release in eight animals, and
      16 weeks after remobilization in eight animals. At immobilization release, the
      average contracture was 76 +/- 24 degrees in group I versus 20 +/- 10 degrees in
      group II (p < 0.001). Sixteen weeks after remobilization, the mean contracture
      was 49 +/- 15 degrees group I versus 11 +/- 10 degrees in group II (p < 0.001).
      When associated with bone perforations and immobilization in forced flexion,
      injury to the posterior capsule results in a severe contracture in the rabbit
      knee.

PMID- 19165744
TI  - Surface-applied insecticide treatments for quarantine control of Japanese beetle,
      Popillia japonica Newman (Coleoptera: Scarabaeidae), larvae in field-grown
      nursery plants.
AB  - BACKGROUND: Japanese beetles, Popillia japonica Newman, are a quarantine
      challenge for nursery shipments from infested to non-infested states. Marathon
      (imidacloprid) and Discus (imidacloprid + cyfluthrin) are approved preharvest
      nursery treatments (US Domestic Japanese Beetle Harmonization Plan; DJHP). This
      study evaluated approved and non-approved (acephate, carbaryl, clothianidin,
      dinotefuran, halofenozide, thiamethoxam, trichlorfon) preharvest treatments,
      optimal rates (labeled 1x, 0.3-0.75 x or 2-3 x) and optimal timings (June, July,
      August and September) to control early-instar (grubs) P. japonica in field
      nurseries. RESULTS: Most insecticides effectively reduced grub densities, except
      for acephate, carbaryl and trichlorfon. Clothianidin, thiamethoxam and
      halofenozide provided grub control equivalent to DJHP standards during most
      years. Across all test years and timings, percentage grub reductions were:
      Marathon (1x: 59.2-100; 3 x: 78.9-100), Discus (1x: 60.7-100), clothianidin (1x:
      96.1-100; 3 x: 97.4-100), thiamethoxam (1x: 75.0-100; 3 x: 80.0-100),
      halofenozide (1x: 70.0-100; 3 x: 90.0-100) and dinotefuran (1x: 13.2-88.2; 3 x:
      71.1-93.4). CONCLUSIONS: July application was more consistent and effective than
      other timings, and higher rates (2x and 3 x) did not generally improve grub
      control. Overall, clothianidin, thiamethoxam and halofenozide (and dinotefuran
      applied in August) were equivalent to current DJHP standards. These insecticides
      may be suitable for DJHP Category 2 states, potentially lowering grower costs.

PMID- 19165745
TI  - Effect of different formulations on tebuconazole residues in stone fruits.
AB  - BACKGROUND: The correlation between pesticide residue levels and formulation of
      an active substance is often not considered, even if it is reasonable to expect
      some differences arising from behaviour during dilution and spraying, from
      adhesion to plant and from degradation. An experimental study to investigate the
      magnitude of tebuconazole residues as a function of different tebuconazole
      formulated products was carried out in Italy. The fungicide was applied as
      wettable powder (WP) and water-dispersible granule (WG) formulations to peach,
      plum, apricot and nectarine orchards, on four different sites. The fruit samples
      gained from the field trials were quantitatively analysed by gas chromatography
      with a nitrogen phosphorus detector (GC/NPD) for tebuconazole residues. RESULTS:
      Tebuconazole residues in the fruits gained from the plot treated with the WP
      formulation, 14 days after application, were in the range 0.01-0.07 mg kg(-1),
      while corresponding residues in the plot treated with the WG formulation were in
      the range 0.01-0.06 mg kg(-1). CONCLUSION: No significant differences in the
      residue levels of tebuconazole could be observed between the trials conducted
      with the WP and the WG formulation.

PMID- 19165746
TI  - Using an F(2) screen to monitor frequency of resistance alleles to Bt cotton in
      field populations of Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae).
AB  - BACKGROUND: In an effort to control the most devastating cotton pest, Helicoverpa
      armigera (Hubner), in Qiuxian County (Hebei, China), Bt cotton has been planted
      almost exclusively since 1998 in this area. Owing to the high insecticidal
      selection pressures in this region, monitoring of Bt resistance in H. armigera is
      necessary so that proactive actions can be implemented before field control
      measures fail. From 2003 to 2005, an F(2) screen was conducted in order to
      monitor Bt resistance in H. armigera populations collected from this area.
      RESULTS: The F(2) screen showed that 15 out of 278 isofemale lines carried
      resistance alleles to Bt cotton. The resistance allele frequency in field
      populations of H. armigera ranged from 0.0119 to 0.0297, with an overall
      frequency of 0.0146 and a 95% confidence interval of 0.0084-0.0225 for the 3 year
      period. This value is greater than the value reported from 1999 (P < 0.05).
      CONCLUSION: A fluctuating but overall increase in resistance allele frequency was
      detected in the field populations of H. armigera in Qiuxian County from 1999 to
      2005. To prevent further increases in Bt resistance frequency in this pest, it is
      necessary to introduce Bt cotton expressing multiple Bt toxins and integrate this
      technology with other tactics for management of this key pest.

PMID- 19165747
TI  - Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in
      vitro measure of GABA transaminase activity.
AB  - A novel pharmacological mechanism of action for the anxiolytic botanical Melissa
      officinalis L. (lemon balm) is reported. The methanol extract was identified as a
      potent in vitro inhibitor of rat brain GABA transaminase (GABA-T), an enzyme
      target in the therapy of anxiety, epilepsy and related neurological disorders.
      Bioassay-guided fractionation led to the identification and isolation of
      rosmarinic acid (RA) and the triterpenoids, ursolic acid (UA) and oleanolic acid
      (OA) as active principles. Phytochemical characterization of the crude extract
      determined RA as the major compound responsible for activity (40% inhibition at
      100 microg/mL) since it represented approximately 1.5% of the dry mass of the
      leaves. Synergistic effects may also play a role.

PMID- 19165748
TI  - Effects of yokukansan, a traditional Japanese medicine, on aggressiveness induced
      by intracerebroventricular injection of amyloid beta protein into mice.
AB  - The effects of yokukansan, a traditional Japanese medicine, on aggressiveness and
      motor activities were examined in mice after injection of amyloid beta protein
      (Abeta) into the lateral ventricle of the brain. The results were compared with
      those of conventional (haloperidol) and atypical (risperidone) antipsychotic
      medicines. A significant increase in aggressiveness was observed on day 7 after
      injection of Abeta, and it lasted until day 28. A single oral administration of
      yokukansan (1.0 g/kg) did not ameliorate the aggressiveness observed on day 7.
      However, a tendency toward amelioration of the aggressiveness was observed after
      the administration of yokukansan (0.5 and 1.0 g/kg) for 1 week (days 7-14). The 3
      week administration (days 7-28) of yokukansan significantly ameliorated the
      aggressiveness in a dose-dependent manner without inhibition of motor activity.
      In contrast, a single administration of intraperitoneal haloperidol (0.03-0.1
      mg/kg) or oral risperidone (0.1-0.3 mg/kg) on day 28 significantly reduced
      aggressiveness in a dose-dependent manner. However, motor activities were
      significantly suppressed. These results suggest yokukansan reduces aggressiveness
      without suppressing physical activity.

PMID- 19165749
TI  - Effect of additives in aqueous formulation on the foliar uptake of dimethomorph
      by cucumbers.
AB  - BACKGROUND: The efficacy enhancement of dimethomorph formulation by several
      adjuvants is thought to be through increased foliar uptake. In order to identify
      the most effective adjuvants, the adjuvancy of 36 additives was examined in
      aqueous formulations in relation to the absorption of dimethomorph by cucumber
      leaves. RESULTS: Polyethylene glycol monohexadecyl ethers with ethylene oxide
      (EO) contents of between 7 and 20, polyethylene glycol monooctadecyl ethers with
      EO contents of between 10 and 20 and polyethylene glycol monooctadecenyl ethers
      with EO contents of between 6 and 20 were effective adjuvants for promoting
      dimethomorph uptake from both aqueous acetone solutions and aqueous wettable
      powder (WP) suspensions into cucumber leaves. Polyethylene glycol monododecyl
      ethers with EO contents of between 7 and 9 were effective in promoting
      dimethomorph uptake from aqueous WP suspensions but less effective relative to
      the other adjuvants tested with aqueous acetone solutions. Foliar uptake of
      dimethomorph was also facilitated by the addition of methyl hexadecanoate, methyl
      octadecenoate and methyl octadecadienoate. CONCLUSIONS: Although the foliar
      uptake of dimethomorph from both aqueous WP suspensions and aqueous acetone
      solutions was greatest in the presence of fatty alcohol ethoxylates generally
      having a C(16) or C(18) lipophile, uptake from aqueous surfactant-acetone
      solutions was, on average, 7.6-fold greater than that from aqueous WP suspensions
      containing surfactant.

PMID- 19165750
TI  - Magnolol enhances pentobarbital-induced sleeping behaviors: possible involvement
      of GABAergic systems.
AB  - This study was performed to investigate whether magnolol enhances pentobarbital
      induced sleeping behaviors through the GABAergic systems. Magnolol prolonged the
      sleeping time induced by pentobarbital. In addition, magnolol increased chloride
      influx in primary cultured cerebellar granule cells. The expression of the
      GABA(A) receptor alpha-subunit was increased selectively by magnolol, but
      magnolol had no effect on the abundance of beta- or gamma-subunits. The
      expression of glutamic acid decarboxylase (GAD) was not influenced by magnolol.
      It is suggested that magnolol may enhance pentobarbital-induced sleeping
      behaviors through the activation of GABAergic systems.

PMID- 19165751
TI  - Evaluation of radioprotective effects of propolis and its flavonoid constituents:
      in vitro study on human white blood cells.
AB  - This in vitro study aimed to evaluate the possible radioprotective effects of the
      natural substances WSDP, caffeic acid, chrysin and naringin on gamma-irradiated
      human white blood cells. The effectiveness of tested compounds was evaluated
      using the alkaline comet assay, the analysis of structural chromosome aberration
      and the cytokinesis-block micronucleus assay. The results obtained by the
      alkaline comet study indicate favourable toxicity profiles of propolis and its
      polyphenolic components, and confirmed the radioprotective abilities comparable
      to the chemical radioprotector AET. WSDP and its polyphenolic components were
      able to reduce the number of necrotic cells. None of tested compounds induced
      significant genotoxicity, but all of them offered a quite measurable protection
      against DNA damage. WSDP was found to be the most effective in diminishing the
      levels of primary and more complex cytogenetic DNA damage in white blood cells.
      Considering its complex composition, to undoubtedly explain the underlying
      mechanisms of cyto/radioprotective effects, further studies are needed.

PMID- 19165752
TI  - Pycnogenol efficiency on glycaemia, motor nerve conduction velocity and markers
      of oxidative stress in mild type diabetes in rats.
AB  - The aim of this study was to describe the effects of Pycnogenol at various doses
      on preprandial and postprandial glucose levels, the levels of thiobarbituric acid
      reactive substances (TBARs) and N-acetyl-beta-d-glucosaminidase (NAGA) and on
      motor nerve conduction velocity (MNCV) in streptozotocin (STZ)-induced diabetic
      rats. Pycnogenol treatment (10, 20, 50 mg/kg body weight (b.w.)/day) lasted for 8
      weeks after induction of diabetes. Pycnogenol significantly decreased elevated
      levels of preprandial glycaemia in treated animals at all doses. At doses of 10
      mg/kg b.w./day and 20 mg/kg b.w./day it significantly decreased elevated levels
      of postprandial glycaemia compared with diabetic non-treated animals. Pycnogenol
      failed to induce a significant decrease of postprandial glycaemia at a dose of 50
      mg/kg b.w./day. Pycnogenol improved significantly the impaired MNCV at doses of
      10 and 20 mg/kg b.w./day compared with non-treated animals. The levels of TBARs
      were elevated in diabetic rats. The levels of NAGA increased gradually despite
      the treatment. Pycnogenol failed to affect the increased levels of TBARs and
      NAGA. Pycnogenollowered the elevated levels of glycaemia and reduced the decline
      in motor nerve conduction velocity in STZ-induced diabetic rats. The effect of
      Pycnogenol on postprandial glycaemic levels and MNCV was not dose-dependent.

PMID- 19165753
TI  - Anticoagulant resistance: a relevant issue in sewer rat (Rattus norvegicus)
      control?
AB  - BACKGROUND: The majority of rat problems in cities are thought to be related to
      defective sewers, and the use of anticoagulant rodenticides in such places is
      often implemented as part of regular urban rodent control. Knowledge pertaining
      to the resistance status of sewer rat populations is non-existent, which may be
      leading to control problems in cities. It has become crucial to provide knowledge
      on the prevalence of resistance and how different control strategies have
      affected its prevalence among sewer rat populations. The prevalence of resistance
      was investigated in six sewer locations in Copenhagen and its suburban area by
      means of the blood clotting response (BCR) test and amplification refractory
      mutation system polymerase chain reaction (ARMS PCR) analysis, and by additional
      sequencing of the VKORC1 gene. The sewer locations were chosen to represent three
      different control strategies: (i) no anticoagulant use for approximately 20
      years; (ii) no anticoagulant use for the last 5 years; (iii) continuous use for
      several decades up to the present. RESULTS: A low level of anticoagulant
      resistance was found in the sewers regardless of control strategy. Surprisingly,
      none of the rats, including the resistant rats, had resistance-related mutations
      in the VKORC1 gene. CONCLUSION: The results of this study suggest that the
      genetic background of anticoagulant resistance may have to be redefined in
      respect of resistance-related changes in the VKORC1 gene.

PMID- 19165754
TI  - Electron ionization mass spectrometric study of substituted alloxazine-5-oxides
      and iso-alloxazine-5-oxide.
AB  - The fragmentation pathways in electron ionization (EI) mass spectra of a series
      of new N(5)-oxides of alloxazines and iso-alloxazine are presented, and compared
      with those of substituted alloxazines and iso-alloxazine. The EI mass spectra of
      these compounds showed characteristic fragmentation pathways A, B and C, started
      by the ejection of atomic oxygen, a HNCO molecule and an OH(*) radical,
      respectively. On the basis of B/E and B(2)/E spectra, the mechanism of
      elimination of the OH(*) radical is discussed. The influence of the methyl
      substituent in the benzene ring of alloxazine on the mass fragmentation pathways
      is described.

PMID- 19165755
TI  - The specific isolation of C-terminal peptides of proteins through a
      transamination reaction and its advantage for introducing functional groups into
      the peptide.
AB  - A novel method for isolating C-terminal peptides from proteolytic digests of
      proteins was developed. Proteins were digested with lysyl endopeptidase (LysC)
      and applied to metal-ion-catalyzed transamination reactions. This reaction
      enabled the selective conversion of an Nalpha-amino group to a carbonyl group.
      Subsequent incubation with p-phenylenediisothiocyanate (DITC) glass effectively
      scavenged the lysine-containing N-terminus and internal peptides. The obtained C
      terminal peptide is open to modification with reagents having virtually any type
      of functionality owing to the reactive alpha-ketocarbonyl group. In this report,
      2,4-dinitrophenylhydrazine (DNPH) was used as an example of a nucleophile to the
      carbonyl group. The isolated C-terminal peptide was modified with DNPH, which
      exhibited signal enhancement, and was sequenced by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

PMID- 19165756
TI  - Validation of QF-PCR in a Korean population.
AB  - OBJECTIVES: Quantitative fluorescence polymerase chain reaction (QF-PCR) is a
      rapid and reliable method for screening common aneuploidies, but it is not an
      accustomed way of testing in Korea. Our objectives were to investigate QF-PCR as
      a means for prenatal aneuploidy screening and to evaluate the short tandem repeat
      (STR) markers in a Korean population. METHOD: Three formats of QF-PCR assays that
      utilize an Elucigene kit (Tepnel Diagnostics), which contains 7 primer pairs
      located on chromosome 21, 16 primers on chromosomes 21, 18, and 13, or 26 primers
      on chromosomes 21, 18, 13, X, and Y were performed. RESULTS: Eight hundred of
      prenatal samples were screened and the results were compared to that of the
      results obtained with conventional cytogenetics. The 31 of 33 (93%) autosomal and
      sex chromosome aneuploidies were detected excluding one case of maternal cell
      contamination and one case of mosaicism respectively; there were no false
      positives. Interestingly, submicroscopic duplication of the D13S634 marker was
      observed in 1.6% of cases. CONCLUSION: For prenatal aneuploidy screening, QF-PCR
      was proved to be efficient and reliable. However, considering the high frequency
      of triallelic patterns of one STR marker that has not been found in other
      populations, careful evaluation is recommended in each STR marker when it is
      applied to different populations.

PMID- 19165757
TI  - Impact of a meaning-centered intervention on job satisfaction and on quality of
      life among palliative care nurses.
AB  - OBJECTIVE: Palliative care (PC) nurses experience several recurrent
      organizational, professional, and individual challenges. To address existential
      and emotional demands, the meaning-centered intervention was recently developed.
      The intervention applied didactic and process-oriented strategies, including
      guided reflections, experiential exercises, and education based on themes of
      Viktor Frankl's logotherapy. The objective of this study was to test its
      efficiency to improve job satisfaction and quality of life in PC nurses from
      three regional districts in Quebec Province, Canada. METHODS: A randomized
      waiting-list group design was conducted, intervention group (n=56) versus waiting
      list group (n=53). Job satisfaction, perception of benefits of working in PC, and
      spiritual and emotional quality of life were measured at pre-, posttest, and 3
      month follow-up. RESULTS: The PC nurses in the experimental group reported more
      perceived benefits of working in PC after the intervention and at follow-up.
      Spiritual and emotional quality of life remained, however, unaffected by the
      intervention. CONCLUSIONS: To explain null findings, theoretical and
      methodological challenges, related to existential interventions, such as choice
      of outcomes, and selection bias (participants recruited were healthy workers) are
      discussed. Future directions and strategies to deal with those issues are
      proposed.

PMID- 19165758
TI  - Parental attitude to participating in long-term follow-up studies of their
      children's health after in utero diagnosis of abnormalities.
AB  - OBJECTIVE: To determine whether parents might be distressed if approached to take
      part in long-term follow-up of their children's health and development. METHODS:
      A short, closed format anonymous questionnaire seeking parental opinion on being
      asked about their child's health was offered to attendees for obstetric
      ultrasound and parents of children attending paediatric cardiology clinics.
      RESULTS: In total, 70% of the 266 respondents were attending for ultrasound and
      approximately 30% paediatric cardiology clinics. In total, 66 respondents had
      children with long-term health problems, 28 with learning difficulties and 61 had
      previously had an abnormal obstetric ultrasound scan. Greater than 90% of parents
      were happy to be contacted and asked questions about their children's health and
      development, regardless of their child's health or their experiences during
      prenatal ultrasonography. CONCLUSIONS: Our results provide reassurance to future
      researchers and ethics committees that studies of children's later health after
      in utero diagnosis of anomalies are unlikely to prove unacceptable to many
      parents.

PMID- 19165759
TI  - Pesticide use in ornamental production: what are the benefits?
AB  - Pest control in ornamental production is challenging owing to the diversity of
      crops grown, the desired aesthetic perfection, the potential economic loss due to
      failure and the multitude of arthropod pests encountered. Agricultural crops of
      less value per acre, such as row crops, can tolerate a certain level of damage
      from arthropod pests without compromising yields. Damage thresholds for
      ornamentals, however, are essentially zero. Pesticides are a viable method of
      protection for such a crop in lieu of alternatives. Therefore, the purpose of
      this paper is to emphasize the importance of pesticides to the ornamental
      industry. Pesticides provide many benefits to ornamental producers, including:
      (1) consistent availability; (2) rapid kill; (3) reliable and consistent control;
      (4) increased crop production and quality; (5) they may be used to prevent
      movement of invasive pests; (6) they are less expensive (in general) than
      alternatives; (7) they may reduce plant pathogenic transmission; (8) they may be
      used in conjunction with natural enemies. Pesticide use will continue to be a
      significant strategy for dealing with arthropod pests so that ornamental
      producers can stay competitive in both national and international markets.

PMID- 19165760
TI  - Causality assessment of liver injury after chronic oral amiodarone intake.
AB  - BACKGROUND/AIM: The number of patients receiving amiodarone will increase in
      future years. As clinically significant hepatotoxicity associated with oral
      amiodarone is infrequent and difficult to predict, a new Bayesian-developed model
      is proposed to help in the causality assessment of amiodarone-induced liver
      injury. METHODS: Incidence of abnormal liver enzymes in patients receiving
      amiodarone was obtained from placebo controlled clinical trials. Published case
      reports of amiodarone-induced hepatotoxicity were identified through a literature
      search. Maximum number of expected hepatotoxicity cases in amiodarone and placebo
      treated patients was calculated using Poisson distribution. The calculated odds
      ratio was used as a Prior Odds (PrO) to subsequent quantification, using a
      Bayesian-approach, of individual amiodarone-induced hepatotoxicity likelihood.
      RESULTS: PrO of amiodarone-induced hepatotoxicity was 0.48. Thirty nine
      amiodarone-associated hepatotoxicity case reports were retrieved. Half of
      published case reports developed an irreversible damage. The amiodarone Bayesian
      model combining information about latency period and period of remission,
      together with analytical parameters properly defines the toxicity profile shown
      in published case reports. The analytical pattern defined by this model is
      different from the one expected if liver injury in published cases was caused by
      other etiologies. CONCLUSIONS: A method based on a Bayesian-approach, which links
      information from clinical trials with clinical hepatotoxicity profile from
      published case reports can be a useful tool for amiodarone-induced liver injury
      causality assessment. At present, this method is limited due to scarcity and
      quality of available data. Further efforts are needed to improve model ability in
      order to identify amiodarone-induced liver injury.

PMID- 19165761
TI  - Modified female calling behaviour in Cry1Ac-resistant Helicoverpa armigera
      (Lepidoptera: Noctuidae).
AB  - BACKGROUND: The resistance risk in Helicoverpa armigera (Hubner) to transgenic
      cotton that expresses Cry1Ac from Bacillus thuringiensis (Bt) has raised concerns
      about the sustainable deployment of Bt cotton. Mating behaviour between resistant
      and susceptible individuals is an important factor that affects resistance
      evolution of the insect. The female calling behaviours of the Cry1Ac-resistant
      strain and its susceptible control were compared in the laboratory to understand
      the difference in mating biology. RESULTS: The proportion of females of the
      resistant strain calling was significantly reduced by 14%, and the age of the
      calling peak was delayed by 1 night compared with that of the susceptible strain.
      During the scotophase, females of the resistant strain started calling more than
      100 min later on nights 3 to 7, and spent 30-100 min less time on nights 2 to 7
      than the susceptible females. The onset time of calling advanced and the time
      spent calling increased as a function of age in both susceptible and resistant
      strains. CONCLUSION: These results indicate that there is a fitness cost in terms
      of the female calling behaviour of the resistant strain. The lower proportion of
      females of the resistant strain showing calling behaviour could reduce the mating
      frequency of the resistant strain. The delayed onset time of calling in the
      resistant strain could reduce its mating time, and a reduction in the time spent
      calling could reduce the attractiveness of resistant females; this could also
      reduce the mating frequency of the resistant strain.

PMID- 19165762
TI  - The cytoplasmic and transmembrane domains of secretor type
      alpha1,2fucosyltransferase confer atypical cellular localisation.
AB  - Carbohydrate structures influence many aspects of cell biology. Manipulating the
      glycosyltransferase enzymes, that sequentially add carbohydrate moieties to
      proteins and lipids as they pass through the Golgi and secretory pathway, can
      alter these carbohydrate epitopes. We previously demonstrated that the eight
      amino acid cytoplasmic tail of alpha1,2fucosyltransferase (FT) contained a
      sequence for Golgi localisation. In this study, we examined the localisation of
      the closely related secretor type alpha1,2fucosyltransferase (Sec) which has a
      smaller, yet apparently unrelated, five amino acid cytoplasmic tail. In contrast
      to the Golgi localisation of FT, Sec displayed atypical cytoplasmic vesicular
      like staining. However, replacing just the five amino acid tail of Sec with FT
      was sufficient to relocalise the enzyme to a perinuclear region with Golgi-like
      staining. The biological significance of this relocalisation was this chimaeric
      enzyme was more effective than FT at competing for N-Acetyl-lactosamine and thus
      was superior in reducing expression of the Galalpha(1,3)Gal xenoepitope.

PMID- 19165763
TI  - Global health partnerships in practice: taking stock of the GAVI Alliance's new
      investment in health systems strengthening.
AB  - Despite a burgeoning literature on global health partnerships (GHPs), there have
      been few studies of how GHPs, particularly those trying to build a bridge between
      horizontal and vertical modes of delivering essential health services, operate at
      global and country levels. This paper will help address this knowledge gap by
      describing and analyzing the GAVI Alliance's early experience with health systems
      strengthening (HSS) to improve immunization coverage and other maternal-child
      health outcomes. To date, the strengths of HSS reside in its potential to
      optimize GAVI's overall investment in immunization, efforts to harmonize with
      other initiatives, willingness to acknowledge risk and identify mitigation
      strategies, engagement of diverse stakeholders, responsiveness to country needs,
      and effective management of an ambitious grant-making enterprise. The challenges
      have been forging a common vision and approach, governance, balancing pressure to
      move money with incremental learning, managing partner roles and relationships,
      managing the "value for money" risk, and capacity building. This mid-point stock
      taking makes recommendations for moving GAVI forward in a thoughtful manner. The
      findings should be of interest to other GHPs because of their larger
      significance. This is a story about how a successful alliance that decided to
      broaden its mandate has responded to the technical, organizational, and political
      complexities that challenge its traditional business model.

PMID- 19165764
TI  - Costing of clinical services in rural district hospitals in northern Vietnam.
AB  - OBJECTIVES: This study aimed to estimate and analyse the "actual" unit cost of
      providing key clinical services in selected rural district hospitals in the North
      of Vietnam. It also examined the relationship between actual costs and the levels
      of cost covered by the corresponding user fees paid by patients. METHODS: This
      was a facility-based costing study which estimates the costs of health care
      services from the perspective of the service providers. Three rural district
      hospitals from three provinces in the North of Vietnam were purposively selected
      for this study. The "step-down" approach was applied. RESULTS: There was little
      difference in the costs of an outpatient visit across the hospitals, but the
      costs of an operation and an inpatient day varied considerably. In terms of cost
      structure, personnel costs accounted for the highest share of total cost of the
      clinical services. The shares of operating cost were considerable while
      depreciation of buildings/equipments made up a small "proportion". The study
      results revealed that the user fee levels were much lower than the actual costs
      of providing the corresponding services. The present study highlights the
      importance of costing data for hospital planning and management.

PMID- 19165765
TI  - Pigment epithelium-derived factor (PEDF) prevents platelet activation and
      aggregation in diabetic rats by blocking deleterious effects of advanced
      glycation end products (AGEs).
AB  - BACKGROUND: Alteration of platelet function contributes to microthrombus
      formation and may play an important role in the pathogenesis of diabetic vascular
      complications. In addition, there is a growing body of evidence that oxidative
      stress generation is involved in platelet activation and aggregation in vivo.
      Since we have recently found that pigment epithelium-derived factor (PEDF)
      inhibits thrombus formation in rats through its anti-oxidative properties, we
      investigated here whether PEDF prevented platelet activation and aggregation in
      diabetic or advanced glycation end products (AGEs)-injected rats. METHODS AND
      RESULTS: Experimental diabetes was induced by injecting streptozotocin to Sprague
      Dawley rats. Diabetic or non-diabetic Sprague-Dawley rats were injected
      intravenously with or without 1 mg AGEs-bovine serum albumin or non-glycated
      bovine serum albumin in the presence or absence of 10 microg PEDF everyday.
      Administration of PEDF or pyridoxal phosphate, an inhibitor of AGEs formation,
      inhibited platelet P-selectin expression and aggregation by suppressing NADPH
      oxidase-driven superoxide generation, and subsequently ameliorated a shortened
      tail vein bleeding time in diabetic rats. Further, intravenous administration of
      AGEs to normal rats mimicked the effects of diabetes on platelet activation and
      bleeding time, which were also blocked by simultaneous administration of PEDF.
      CONCLUSIONS: These results demonstrated for the first time that PEDF inhibited
      platelet activation and aggregation in diabetic rats through its anti-oxidative
      properties. Our present study suggests that PEDF may play a protective role
      against diabetic vascular complications by attenuating the deleterious effects of
      AGEs on platelets.

PMID- 19165766
TI  - Preparation and in vivo evaluation of apatite/collagen packed composite by
      alternate immersion method and Newton press.
AB  - Further development of bio-compatible, bio-absorbable, and osteo-conductive bio
      materials is desired for bone grafts in dental and medical clinics. One candidate
      material might be a high-density apatite/collagen composite, which cures
      relatively large bone defects. To produce such a composite, we freeze-dried type
      I collagen solution, cross-linked the formed sponge by 2 wt % glutaraldehyde,
      immersed the insoluble sponge in CaCl(2) and Na(2)HPO(4) solutions alternately
      five times, and compacted the sponge by Newton press at 5000 kgf. For comparison,
      cross-linked collagen without alternate immersion was also pressed. SEM/EPMA,
      XRD, and FTIR analyses clarified that alternate immersion successfully coated the
      collagen sponge with hydroxyapatite. Packed apatite/collagen composite and
      collagen disks 6 mm in diameter and 0.5 mm in height were implanted in the
      subperiostea of rabbit tibiae for 2, 4, 8, and 12 weeks to assess bio
      compatibility, bio-absorbability, and osteo-conductivity. Histological
      observations showed that the packed apatite/collagen composite was biocompatible,
      osteo-conductive for up to 8 weeks, and largely bio-absorbed at 12 weeks, while
      the packed collagen sponge caused an undesirable foreign body reaction, which
      worsened with the implantation period. The overall findings suggest that this
      packed apatite/collagen composite might be used as a new bio-absorbable bone
      graft material.

PMID- 19165767
TI  - Antibacterial effect of silver-zeolite containing root-canal filling material.
AB  - The aim of this study was to determine the in vitro antibacterial effect of two
      experimental glass ionomer cements (GICs) on Streptococcus milleri,
      Staphylococcus aureus, and Enterococcus faecalis after 24 and 48 h incubation by
      using the agar diffusion inhibitory test. Silver zeolite (SZ) was added at 0.2
      and 2% mass fraction concentration to GIC (Endion). The control group was Endion
      with no SZ. Each of them were prepared to uniform size using a custom-made Teflon
      mold, and the GIC materials were prepared to form disks (n = 5 per group). The
      effect of these materials on the growth of three bacteria associated with
      endodontic infections was determined using the agar diffusion inhibitory test.
      The amounts of silver ion release from these materials were measured with atomic
      absorption spectrophotometry at 10 min, 24- and 48-h periods. The pH of samples
      was measured with a pH-meter at 10 min, 24- and 48-h periods. After the
      incubation period, the agar plates were evaluated and the degrees of bacterial
      inhibition were measured in millimeters. A comparison of the mean of the test
      materials was statistically different in each group of specimens (p < 0.05).
      Between the two tested materials 2% SZ containing GIC showed the largest zone of
      inhibition on the agar plates of all the tested strains (p < 0.05). The most
      inhibition in bacterial growth occurred in E. faecalis. Adding 2% SZ to GIC
      resulted in a significant increase in the silver release into deionized water.
      This study demonstrated that GIC had an inhibitory affect on Streptococcus
      milleri, Staphylococcus aureus, and Enterococcus faecalis and that adding SZ
      increases that affect proportional to its concentration.

PMID- 19165768
TI  - Collagen nanofilm immobilized on at surfaces by electrodeposition method.
AB  - A simple electrodeposition method is presented for the preparing of collagen
      nanofilms (EAT) on anodic oxidized titanium surfaces (AT). The nanofilms were
      observed by scanning electron microscopy and atomic force microscopy. Functional
      TiOx layers with anionic groups of --PO(4), --SO(4) and --OH were investigated on
      the AT surface by X-ray photoelectron spectroscopy; X-ray diffraction results
      indicated that the AT surface was composed mainly of anatase and rutile. The
      bioactive electrodeposited TiOx layers on the AT surface showed lower water
      contact angles and higher surface energy than pure titanium surfaces (CT) and
      displayed higher collagen molecule immobilization.

PMID- 19165769
TI  - Pivoting system fracture in a bileaflet mechanical valve: a case report.
AB  - A leaflet escape occurred in a low profile bileaflet mechanical prosthesis
      manufactured by TRI-Technologies that had been implanted for 3 years in the
      mitral position of a 32 year old patient. The escaped leaflet had embolized and
      was subsequently located by an abdominal computerized axial tomography scan and
      ultrasound in the terminal portion of the aortic bifurcation. The embolized
      leaflet was removed 3 months after valve replacement surgery. In an attempt to
      determine the cause of the escape the retrieved embolized leaflet was
      investigated. Techniques employed included visual examination aided by stereo
      microscopy, x-ray imaging and scanning electron microscopy. One of the ears had
      fractured and was missing from the leaflet. Chipping was observed at the leaflet
      ear position on both the inflow and outflow surfaces. Visual and SEM observations
      found fractographic river-lines that indicated an apparent origin at the inflow
      surface of the ear nearest to the straight 'B-datum' line or coaptation edge. The
      origin seemed to be in the radius between the leaflet ear and the leaflet body.
      SEM observation of the remaining intact ear showed wear marks on both the inflow
      and outflow sides of the leaflet ear that corresponded to the suspected origin of
      fracture. It is believed that the use of boron alloyed pyrolytic carbon material
      and the leaflet's homogeneous monolithic structural design were factors that
      contributed to this adverse event.

PMID- 19165770
TI  - No efficacy of silver bone cement in the prevention of methicillin-sensitive
      Staphylococcal infections in a rabbit contaminated implant bed model.
AB  - Data from literature showed that a new type of metallic silver PMMA cement had
      good results in infection prophylaxis. This study investigated the in vivo
      efficacy of silver cement in the prevention of methicillin-sensitive
      Staphylococcal infections, compared to plain and tobramycin-containing cement. In
      48 rabbits, 0.6% silver, 1% silver, plain, or tobramycin PMMA cement was injected
      into the femoral medullary canal after contamination with 10(5), 10(6), or 10(7)
      colony forming units (CFU) Staphylococcus aureus. After 14 days, bone was
      collected for bacteriology and histopathology. All plain and silver cement
      rabbits were infected, whereas only two tobra rabbits were infected (p < 0.001).
      The number of bacteria cultured ((10)logCFU) from bone adjacent to the cement,
      was 6.4 +/- 0.3 and 6.1 +/- 0.3 for the 0.6% and 1% silver rabbits. For the
      rabbits with plain and tobra cement, this was 6.2 +/- 0.2 (p > 0.95) and 0.0 +/-
      0.0 (p < 0.001), respectively. Two tobra rabbits had a positive culture of a
      distal bone sample. Histological sections of plain, 0.6%, and 1% silver rabbits
      all showed signs of infection; these signs were absent in the tobra rabbits.
      Silver and plain cement were not effective in preventing infection, whereas tobra
      cement was effective. As silver cement predominantly exhibits an antimicrobial
      effect at the direct cement surface, this cement seems less useful in situations
      where there are bacteria present in surrounding tissues, like revision surgery.
      Whether silver cement has relevance in the prevention of bacterial colonization
      of cement remains to be determined.

PMID- 19165771
TI  - Postimplantation pressure testing and characterization of laser bonded
      glass/polyimide microjoints.
AB  - The stability of the laser bonded titanium coated glass/polyimide microjoints
      were studied in vivo by implanting on a rat brain surface for 10 days. In the
      current state, the strength of the joints were measured by a specially designed
      instrument called "pressure test" equipment where the samples were subjected to a
      variable pressure load (using high pressure nitrogen) controlled by a pressure
      regulator. The strength of the joints seems to degrade by about 28% as a result
      of soaking in rat brain. The bond degradation in rat brain implants is similar
      compared with those soaked in artificial cerebrospinal fluid (CSF) solution.
      Polyimide uptakes water through existing pores in it and also water gets in the
      joint region through the edges of the samples. Water might have caused oxidation
      of the chemical bonds which are thought to have formed by the laser fabrication
      process. A separate set of samples were created using same parameters for testing
      the hermeticity of the laser bonds. The samples were also exposed to rat brain
      CSF and were tested for hermiticity at the end of 10 days exposure time. It was
      observed that the implanted samples retained their hermeticity although the bond
      strength degraded by about 28%.

PMID- 19165772
TI  - Coumestrol promotes proliferation and osteoblastic differentiation in rat bone
      marrow stromal cells.
AB  - Although the effects of coumestrol on osteoblasts and osteoclasts can be
      summarized as increasing the bone density and preventing bone resorption, direct
      and detailed effects of coumestrol on bone marrow stromal cells remain obscure.
      In the present study, the effects of coumestrol on proliferation and osteoblastic
      differentiation of rat bone marrow stromal cells (BMSCs) have been investigated;
      the regulative effect of coumestrol on BMSCs and skeletal system has also been
      discussed. The results showed that treatment with coumestrol increased cellular
      activities (analyzed by MTT assay), alkaline phosphatase (ALP), type I collagen
      and osteocalcin (OCN) activity as well as the protein and gene expression of OPG,
      gene expression ratio of OPG/RANKL and gene expression of estrogen receptor
      alpha(ERalpha). These results demonstrate that phytoestrogen coumestrol has a
      direct enhancing effect on the proliferation and osteogenic differentiation of
      bone marrow stromal cells, which would lead to stimulation of bone formation, and
      it can also protect the whole skeletal system by regulating OPG/RANKL expression,
      and these effects may be mediated by ERalpha.

PMID- 19165773
TI  - A kernel-based method to determine optimal sampling times for the simultaneous
      estimation of the parameters of rival mathematical models.
AB  - When several models are proposed for one and the same process, experimental
      design techniques are available to design optimal discriminatory experiments.
      However, because the experimental design techniques are model-based, it is
      important that the required model predictions are not too uncertain. This
      uncertainty is determined by the quality of the already available data, since low
      quality data will result in poorly estimated parameters, which on their turn
      result in uncertain model predictions. Therefore, model discrimination may become
      more efficient and effective if this uncertainty is reduced first. This can be
      achieved by performing dedicated experiments, designed to increase the accuracy
      of the parameter estimates. However, performing such an additional experiment for
      each rival model may undermine the overall goal of optimal experimental design,
      which is to minimize the experimental effort. In this article, a kernel-based
      method is presented to determine optimal sampling times to simultaneously
      estimate the parameters of rival models in a single experiment. The method is
      applied in a case study where nine rival models are defined to describe the
      kinetics of an enzymatic reaction (glucokinase). The results clearly show that
      the presented method performs well, and that a compromise experiment is found
      which is sufficiently informative to improve the overall accuracy of the
      parameters of all rival models, thus allowing subsequent design of an optimal
      discriminatory experiment.

PMID- 19165774
TI  - Theoretical study on the gas-phase reaction mechanism between nickel monoxide and
      methane for syngas production.
AB  - The comprehensive mechanism survey on the gas-phase reaction between nickel
      monoxide and methane for the formation of syngas, formaldehyde, methanol, water,
      and methyl radical has been investigated on the triplet and singlet state
      potential energy surfaces at the B3LYP/6-311++G(3df, 3pd)//B3LYP/6-311+G(2d, 2p)
      levels. The computation reveals that the singlet intermediate HNiOCH(3) is
      crucial for the syngas formation, whereas two kinds of important reaction
      intermediates, CH(3)NiOH and HNiOCH(3), locate on the deep well, while CH(3)NiOH
      is more energetically favorable than HNiOCH(3) on both the triplet and singlet
      states. The main products shall be syngas once HNiOCH(3) is created on the
      singlet state, whereas the main products shall be methyl radical if CH(3)NiOH is
      formed on both singlet and triplet states. For the formation of syngas, the
      minimal energy reaction pathway (MERP) is more energetically preferable to start
      on the lowest excited singlet state other than on the ground triplet state. Among
      the MERP for the formation of syngas, the rate-determining step (RDS) is the
      reaction step for the singlet intermediate HNiOCH(3) formation involving an
      oxidative addition of NiO molecule into the C-H bond of methane, with an energy
      barrier of 120.3 kJ mol(-1). The syngas formation would be more effective under
      higher temperature and photolysis reaction condition.

PMID- 19165775
TI  - N(2)O in small para-hydrogen clusters: Structures and energetics.
AB  - We present the minimum-energy structures and energetics of clusters of the linear
      N(2)O molecule with small numbers of para-hydrogen molecules with pairwise
      additive potentials. Interaction energies of (p-H(2))-N(2)O and (p-H(2))-(p-H(2))
      complexes were calculated by averaging the corresponding full-dimensional
      potentials over the H(2) angular coordinates. The averaged (p-H(2))-N(2)O
      potential has three minima corresponding to the T-shaped and the linear (p-H(2))
      ONN and (p-H(2))-NNO structures. Optimization of the minimum-energy structures
      was performed using a Genetic Algorithm. It was found that p-H(2) molecules fill
      three solvation rings around the N(2)O axis, each of them containing up to five p
      H(2) molecules, followed by accumulation of two p-H(2) molecules at the oxygen
      and nitrogen ends. The first solvation shell is completed at N = 17. The
      calculated chemical potential oscillates with cluster size up to the completed
      first solvation shell. These results are consistent with the available
      experimental measurements.

PMID- 19165776
TI  - Imaging mass spectrometry for examining localization of polymeric composition in
      matrix-assisted laser desorption/ionization samples.
AB  - The localization of polymeric composition in samples prepared for matrix-assisted
      laser desorption/ionization (MALDI) analysis has been investigated by imaging
      mass spectrometry. Various matrices and solvents were used for sample spot
      preparation of a polybutyleneglycol (PBG 1000). It was shown that in visibly
      homogeneous spots, prepared using the 'dried droplet' method, separation between
      matrix and polymer takes place. Moreover, using alpha-cyano-4-hydroxycinnamic
      acid (CCA) as matrix and methanol as solvent molecular mass separation of the
      polymer homologues in the spots was detectable. In contrast to manually spotted
      samples, dry spray deposition results in homogeneous layers showing no separation
      effects.

PMID- 19165777
TI  - Acid hydrolysis followed by matrix-assisted laser desorption/ionization mass
      spectrometry for the rapid diagnosis of serum protein biomarkers in patients with
      major depression.
AB  - We have developed a technique combining acid hydrolysis with matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for
      the rapid study of the changes in the levels of positive and negative acute phase
      protein biomarkers in the sera of patients suffering from major depression. The
      serum proteins were first precipitated using an organic solvent; after
      separation, they were subjected to hydrochloric acid hydrolysis (6 M HCl) for 10
      min. The resulting peptides were characterized using MALDI-TOF MS. Short-term
      treatment of the serum proteins with HCl efficiently removed interference from
      the abundant protein - albumin - and produced abundant peptide ion signals in the
      range of m/z 4000-10 000. This approach allowed us to rapidly detect the peptide
      ions originating from transferrin (a common negative acute phase protein) and
      fibrinogen (a common positive acute phase protein). The average ratios and
      (standard deviations) of the ion signals derived from transferrin/fibrinogen were
      3.58 (+/-1.93) for the healthy control subjects and 1.02 (+/-0.52) for the
      patients suffering from major depression. The differences in
      transferrin/fibrinogen ratios between healthy controls and patients suggest that
      major depression will induce internal inflammation and cause either an increase
      in the level of fibrinogen or a decrease in the level of transferrin.

PMID- 19165778
TI  - Comparison of atmospheric pressure photoionization and electrospray ionization
      mass spectrometry for the analysis of UV filters.
AB  - A comparison was made between the electrospray ionization (ESI) and atmospheric
      pressure photoionization (APPI) tandem mass spectrometric (MS/MS) responses of
      eleven ultraviolet (UV) filters. Four of the target compounds were favourably
      ionized in negative ion mode, and the other seven compounds in positive ion mode.
      For nine of the compounds APPI generated a similar response to that of ESI, but
      the APPI signal-to-noise (S/N) ratios were 1.3-60 times higher. The two most
      polar of the UV filter compounds (PBSA and BP-4) were more efficiently ionized by
      ESI, offering higher signal intensities and lower detection limits. APPI was,
      however, less susceptible to ion suppression than ESI when real samples were
      injected. In order to optimize the APPI conditions different dopant solvents were
      examined to enhance the efficiency of the photoionization process. Among the
      evaluated dopants, toluene was selected as the best compromise. At a toluene flow
      rate of 10% of the solvent flow rates the ionization response increased by a
      factor of 40-50 over the use of no dopant for the compounds in positive ion mode
      and by more than 300 for the compounds in negative ion mode.

PMID- 19165779
TI  - Mechanical properties of small-diameter polyurethane vascular grafts reinforced
      by weft-knitted tubular fabric.
AB  - Polyester filament yarns of different Deniers were knitted into tubular fabrics
      with different densities and thicknesses on a specially designed weft-knitting
      machine. The developed tubular fabric was used to reinforce polyurethane vascular
      graft and thus a kind of composite vascular graft was fabricated with a small
      inner diameter of 4 mm. Tensile properties of the reinforced composite vascular
      grafts were compared with the control tubular fabric and the pure PU vascular
      grafts. Elasticity and strength of the reinforced vascular grafts were improved
      compared with the weft-knitted tubular fabrics. Strength of the reinforced
      composite vascular grafts was almost 5-10 times of the strength of the pure PU
      vascular grafts. As the PU content increased in the reinforced composite vascular
      grafts, the wall thickness of the vascular graft and its strength increased, but
      the initial modulus of the reinforced composite vascular grafts remained similar
      to that of the weft-knitted tubular fabric, and the PU content showed little
      influence on the initial modulus of the reinforced composite vascular grafts.
      Microporous structure can also be fabricated in the wall of the reinforced
      composite vascular grafts.

PMID- 19165780
TI  - Biomimetic, bioactive etheric polyphosphazene-poly(lactide-co-glycolide) blends
      for bone tissue engineering.
AB  - The long-term goal of this work is to develop biomimetic polymer-based systems
      for bone regeneration that both allow for neutral pH degradation products and
      have the ability to nucleate bonelike apatite. In this study, the etheric
      biodegradable polyphosphazene, poly[(50%ethyl
      glycinato)(50%methoxyethoxyethoxy)phosphazene] (PNEG(50)MEEP(50)) was blended
      with poly(lactide-co-glycolide) PLAGA and studied their ability to produce high
      strength degradable biomaterials with bioactivity. Accordingly, two blends with
      weight ratios of PNEG(50)MEEP(50) to PLAGA 25:75 (BLEND25) and 50:50 (BLEND50)
      were fabricated using a mutual solvent approach. Increases in PNEG(50)MEEP(50)
      content in the blend system resulted in decreased elastic modulus of 779 MPa when
      compared with 1684 MPa (PLAGA) as well as tensile strength 7.9 MPa when compared
      with 25.7 MPa (PLAGA). However, the higher PNEG(50)MEEP(50) content in the blend
      system resulted in higher Ca/P atomic ratio of the apatite layer 1.35 (BLEND50)
      when compared with 0.69 (BLEND25) indicating improved biomimicry. Furthermore,
      these blends supported primary rat osteoblast adhesion and proliferation with an
      enhanced phenotypic expression when compared with PLAGA. These findings establish
      the suitability of PNEG(50)MEEP(50)-PLAGA biodegradable blends as promising
      bioactive materials for orthopedic applications.

PMID- 19165781
TI  - In vivo performance of selective electron beam-melted Ti-6Al-4V structures.
AB  - Highly porous titanium structures are widely used for maxillofacial and
      orthopedic surgery because of their excellent mechanical properties similar to
      those of human bone and their facilitation of bone ingrowth. In contrast to
      common methods, the generation of porous titaniumproducts by selective electron
      beam melting (SEBM), an additive manufacturing technology, overcomes difficulties
      concerning the extreme chemical affinity of liquid titanium to atmospheric gases
      which consequently leads to strongly reduced ductility of the metal. The purpose
      of this study was to assess the suitability of a smooth compact and a porous Ti
      6Al-4V structure directly produced by the SEBM process as scaffolds for bone
      formation. SEBM-processed titanium implants were placed into defects in the
      frontal skull of 15 domestic pigs. To evaluate the direct contact between bone
      and implant surfaces and to assess the ingrowth of osseous tissue into the porous
      structure, microradiographs and histomorphometric analyses were performed 14, 30,
      and 60 days after surgery. Bone ingrowth increased significantly during the
      period of this study. After 14 days the most outer regions of the implants were
      already filled with newly formed bone tissue (around 14%). After 30 days the bone
      volume inside the implants reached almost 30% and after 60 days abundant bone
      formation inside the implants attained 46%. During the study only scarce bone
      implant contact was found around all implants, which did not exceed 9% around
      compact specimens and 6% around porous specimens after 60 days. This work
      demonstrates that highly porous titanium implants with excellent
      interconnectivity manufactured using the SEBM method are suitable scaffolds for
      bone ingrowth. This technique is a good candidate for orthopedic and
      maxillofacial applications.

PMID- 19165782
TI  - Investigation of mechanical properties of soft hydrogel microcapsules in relation
      to protein delivery using a MEMS force sensor.
AB  - This article reports the investigation of mechanical properties of alginate
      chitosan microcapsules and the relation to protein delivery. For microscale
      compression testing, a system based on a microelectromechanical systems (MEMS)
      capacitive force sensor was developed. The bulk microfabricated capacitive force
      sensors are capable of resolving forces up to 110 microN with a resolution of
      33.2 nN along two independent axes. The monolithic force sensors were directly
      applied to characterizing mechanical properties of soft hydrogel microparticles
      without assembling additional end-effectors. Protein-loaded alginate-chitosan
      microcapsules of approximately 20 mum in diameter were prepared by an emulsion
      internal gelation-polyelectrolyte coating method. Young's modulus values of
      individual microcapsules with 1, 2, and 3% chitosan coating were determined
      through microscale compression testing in both distilled deionized (DDI) water
      and pH 7.4 phosphate-buffered saline (PBS). Protein release rates were also
      determined in DDI water and PBS. Finally, protein release rates were correlated
      with mechanical properties of the microcapsules.

PMID- 19165783
TI  - Response of UMR 106 cells exposed to titanium oxide and aluminum oxide
      nanoparticles.
AB  - The cytotoxicity potential of TiO(2) and Al(2)O(3) nanoparticles (NP) in UMR 106
      cells was studied by evaluating the lysosomal activity with neutral red uptake
      assay (NR), and the mitochondrial activity with tetrazolium MTT test. Different
      NP concentrations (10-300 microg/mL range) were used. A significant (p < 0.001)
      increase in the absorbance (stronger for TiO(2) NP) was detected in both NR and
      MTT assays after 24-h exposure to the NP. However, the total cell proteins and
      the cell proliferation rate demonstrated (p < 0.05) that the cell viability
      decreased after 96 h exposure to NP. The formation of NP-containing vesicles
      within the cells was observed by transmission electronic microscopy. Such event
      could explain the high cellular activity detected during the early stages of
      exposure not related to the increase in cell viability. Results showed that the
      effects of NP on cell lines are dependent on the chemical composition of the
      particles, their concentration, exposure time, and the type of treated cell. It
      can be concluded that the presence of TiO(2) and Al(2)O(3) NP in the cell
      surroundings can lead to cytotoxic effects. In the case of osteoblast cells, such
      events may induce osseointegration failures in orthopedic and dental implants
      that release NP.

PMID- 19165784
TI  - Microphase separation structure influences protein interactions with
      poly(urethane urea) surfaces.
AB  - Microphase separation is an important characteristic of polyurethane copolymer
      biomaterials. An improved understanding of the effects of microphase structure on
      protein interactions with the polymeric biomaterial surface is essential for the
      development and application of new biomaterials intended for implantation into
      the body. In this study, an array of atomic force microscopy (AFM) techniques
      were used to visualize the phase separation structure in a hydrated poly(urethane
      urea) (PUU) material and to correlate that structure with molecular interactions
      at the molecular level. Sequential in situ AFM phase images showed that the hard
      domains present a dynamic environment and undergo rearrangement and enrichment at
      the surface when hydrated. Adhesion forces measured using a protein-modified AFM
      probe suggests that the PUU surface became less adhesive to protein with
      hydration time, consistent with other physical characterizations. Force
      measurements were used to quantify and correlate mechanical properties and local
      adhesion forces for bovine serum albumin, and results showed that low adhesion
      forces were primarily associated with polar hard domain regions. A nanogold
      labeled protein conjugate was used to visualize individual protein adsorption to
      the separate microstructures on the PUU surface, with preferential protein
      adsorption seen on the more apolar hydrophobic soft segment regions. Together,
      the results suggest that the microphase separation structure mediates local
      surface microenvironments that influence biological interactions with the
      surface.

PMID- 19165785
TI  - Enzymatically crosslinked porous composite matrices for bone tissue regeneration.
AB  - Three-dimensional porous hydroxyapatite/collagen (HA/Coll) composites with a
      random pore structure were obtained by freeze-drying and crosslinked by an
      enzymatic treatment using microbial transglutaminase (mTGase). The procedure
      resulted in improved mechanical strength and thermal stability of the scaffolds.
      The scaffolds were characterized in terms of their stability (Coll release,
      swelling, collagenase-mediated degradation), thermal properties
      (thermogravimetric analysis, differential scanning calorimetry), mechanical
      behavior under compression and cell compatibility. Enzymatic treatment stabilized
      the sponges to water vapors, with measurable swelling ratio between 100% for
      HA/Coll/mTGase 0/100 to 5% for HA/Coll/mTGase 80/20. Weight loss in water due to
      Coll release was between 2 and 10% in mTGase-crosslinked samples and decreased
      with increasing HA content. Cultures of MG63 osteoblast-like cells and human
      umbilical vein endothelial cells (HUVEC) showed good adhesion and proliferation
      on the scaffolds, good viability (through MTT test, 100-150% of control), and
      good differentiation (alkaline phosphatase, up to 40 UI/L with respect to 35 UI/L
      for control).

PMID- 19165786
TI  - Effects of mechanical load on the expression and activity of hyaluronidase in
      cultured synovial membrane cells.
AB  - Hyaluronan (HA) has lubricating and buffering functions in joints. Mechanical
      load is a regulatory factor of HA metabolism in joints, and HA synthesis by
      synovial membrane cells is modulated by mechanical load. However, the effects of
      mechanical load on HA catabolism by hyaluronidase (HYAL) in synovial membrane
      cells remain unclear. The purpose of this study was to evaluate the effects of
      cyclic tensile load on the expression and activity of HYAL in synovial membrane
      cells. A cyclic tensile load of 22.8% cell elongation was applied to cultured
      rabbit synovial membrane cells for 3 to 48 h with or without cycloheximide. HYAL1
      and HYAL2 mRNA levels were evaluated by means of real-time polymerase chain
      reaction (PCR) analysis. HYAL activity in the cell culture was analyzed by means
      of HA zymography with or without HYAL2-small interfering (si) RNA. Levels of both
      HYAL1 and HYAL2 mRNA were up-regulated significantly (p < 0.01) by the cyclic
      tensile load with or without cycloheximide. HYAL activity was detected in the
      loaded cell cultures and was suppressed substantially by HYAL2-siRNA. HYAL
      activity was undetectable in unloaded cell cultures. These results show that a
      cyclic tensile load induces the expression and activity of HYAL in synovial
      membrane cells, suggesting that increased HYAL by mechanical load affects HA
      catabolism in synovial fluid.

PMID- 19165787
TI  - Bone remodeling in a new biomimetic polymer-composite hip stem.
AB  - Adaptive bone remodeling is an important factor that leads to bone resorption in
      the surrounding femoral bone and implant loosening. Taking into account this
      factor in the design of hip implants is of clinical importance, because it allows
      the prediction of the bone-density redistribution and enables the monitoring of
      bone adaptation after prosthetic implantation. In this article, adaptive bone
      remodeling around a new biomimetic polymer-composite-based (CF/PA12) hip
      prosthesis is investigated to evaluate the amount of stress shielding and bone
      resorption. The design concept of this new prosthesis is based on a hollow
      substructure made of hydroxyapatite-coated, continuous carbon fiber (CF)
      reinforced polyamide 12 (PA12) composite with an internal soft polymer-based
      core. Strain energy density theory coupled with 3D Finite Element models is used
      to predict bone density redistributions in the femoral bone before and after
      total hip replacement (THR) using both polymer-composite and titanium (Ti) stems.
      The result of numerical simulations of bone remodeling revealed that the CF/PA12
      composite stem generates a better bone density pattern compared with the Ti-based
      stem, indicating the effectiveness of the composite stem to reduce bone
      resorption caused by stress-shielding phenomenon. This may result in an extended
      lifetime of THR.

PMID- 19165788
TI  - Sensitivity of insulin production from encapsulated islets to endotoxin
      stimulated macrophage inflammatory mediators.
AB  - Chronic inflammation may compromise function of implanted encapsulated islets.
      Increased purity of alginate used for encapsulation prolongs encapsulated graft
      function, correlating with decreased presence of impurities like bacterial
      endotoxin. Limits for endotoxin contamination in biomaterials based on indirect
      inhibition of function of embedded cells have yet to be established. In a
      coculture system with RAW 264.7 monocyte/macrophage cells in the presence of 50
      ng/mL murine recombinant gamma-interferon (mrIFN-gamma), the insulin response to
      glucose challenge of both rat and pig unencapsulated islets was prevented by
      endotoxin (LPS) in the medium down to 0.3 EU/mL (LOEL), but not 0.06 EU/mL
      (NOEL). Evaluation of nitrite concentrations in supernatants revealed that pig
      islets were more resistant to LPS-stimulated macrophage mediators than rat
      islets. Encapsulation in highly purified alginate produced little change in
      observed inhibitory effects of macrophage-generated nitric oxide (NO) toward
      islet function. Chemically released NO was much less effective in inhibiting
      insulin responsiveness to glucose challenge than was coculture of islets with LPS
      and mrIFN-gamma-stimulated RAW 264.7. These results taken together with other
      data suggest that an upper limit of 0.3 EU/mL LPS within the encapsulating
      alginate will not impair the function of implanted encapsulated islets by toxic
      concentrations of macrophage-mediated inflammatory agents.

PMID- 19165790
TI  - Improving the affinity of fibroblasts for bacterial cellulose using carbohydrate
      binding modules fused to RGD.
AB  - The attachment of cells to biomedical materials can be improved by using adhesion
      sequences, such as Arg-Gly-Asp (RGD), found in several extracellular matrix
      proteins. In this work, bifunctional recombinant proteins, with a Cellulose
      Binding Module (CBM), from the cellulosome of Clostridium thermocellum and cell
      binding sequences-RGD, GRGDY-were cloned and expressed in E.coli. These RGD
      containing cellulose binding proteins were purified and used to coat bacterial
      cellulose fibres. Its effect on the cell adhesion/biocompatibility properties was
      tested using a mouse embryo fibroblasts culture. Bacterial cellulose (BC)
      secreted by Gluconacetobacter xylinus (=Acetobacter xylinum) is a material with
      unique properties and promising biomedical applications. CBMs adsorbs
      specifically and tightly on cellulose. Thus, they are a useful tool to address
      the fused RGD sequence (or other bioactive peptides) to the cellulose surface, in
      a specific and simple way. Indeed, fibroblasts exhibit improved ability to
      interact with bacterial cellulose sheets coated with RGD-CBM proteins, as
      compared with cellulose treated with the CBM, that is, without the adhesion
      peptide. The effect of the several fusion proteins produced was analyzed.

PMID- 19165789
TI  - A bovine acellular scaffold for vocal fold reconstruction in a rat model.
AB  - With a rat model of vocal fold injury, this study examined the in vivo host
      response to an acellular xenogeneic scaffold derived from the bovine vocal fold
      lamina propria, and the potential of the scaffold for constructive tissue
      remodeling. Bilateral wounds were created in the posterior vocal folds of 20
      rats, and bovine acellular scaffolds were implanted into the wounds unilaterally,
      with the contralateral vocal folds as control. The rats were humanely sacrificed
      after 3 days, 7 days, 1 month, and 3 months, and the coronal sections of their
      larynges were examined histologically. Expressions of key matrix proteins
      including collagen I, collagen III, elastin, fibronectin, hyaluronic acid, and
      glycosaminoglycans (GAGs) were quantified with digital image analysis.
      Significant infiltration of host inflammatory cells and host fibroblasts in the
      scaffold implant was observed in the acute stage of wound repair (3 days and 7
      days postsurgery). The mean relative densities of collagen I, collagen III, and
      GAGs in the implanted vocal folds were significantly higher than those in the
      control after 3 days, followed by gradual decreases over 3 months. Histological
      results showed that the scaffolds were apparently degraded by 3 months, with no
      fibrotic tissue formation or calcification. These preliminary findings suggested
      that the bovine acellular scaffold could be a potential xenograft for vocal fold
      regeneration.

PMID- 19165791
TI  - In vitro elution of moxifloxacin from cancellous bone allografts.
AB  - The characteristics of cancellous bone allografts as carriers of moxifloxacin are
      described. Particles of cancellous bone were compressed into a wire-mesh cylinder
      and impregnated into a solution of moxifloxacin for different time periods. Five
      replicas were impregnated for 1 h; another five for 24 h; and another five for 48
      h. Impregnated allografts were then transferred into vials containing 5 ml of
      Mueller-Hinton broth and incubated at 37 degrees C. Broth was replaced daily.
      Concentrations of moxifloxacin in broth were determined after analysis by an high
      performance liquid chromatography system. Moxifloxacin was eluted at very high
      concentrations within the first days. Concentrations remained above 100 microg/ml
      until day 8 and above 40 microg/ml until day 20. It is concluded that cancellous
      bone allografts may allow the adequate in vitro elution of moxifloxacin. The
      latter results support their application in experimental models of osteomyelitis.

PMID- 19165792
TI  - Hydroxyapatite crystals biologically inspired on titanium by using an organic
      template based on the copolymer of acrylic acid and itaconic acid.
AB  - Hydroxyapatite coating on metal implants is an effective method to enhance
      bioactive properties of the metal surface. We report here a method to coat the Ti
      6Al-4V alloy with hydroxyapatite crystals. After alkaline/heat treatment, the
      spontaneous growth of organoapatite on titanium alloy surface involves sequential
      preadsorption of titanium isopropoxide (TIPO) and the copolymer of acrylic acid
      and itaconic acid on the metal, followed by exposure to simulated body fluid
      (SBF). The organoapatite characterization of the coating was carried out by
      scanning electron microscopy, energy dispersive spectrometer, and X-ray
      diffraction. The copolymer of acrylic acid and itaconic acid overlayer which is
      rich of carboxylate groups can lead to the deposition of needle-like and
      homogeneous HA on the surface after immersion in SBF.

PMID- 19165793
TI  - Experiment, thermal simulation, and characterizations on transmission laser
      coating of hydroxyapatite on metal implant.
AB  - Coating of bioceramic material, Hydroxyapatite (HAp), on metal implant has
      attracted many attentions in biomedical industry recently because its combination
      of good mechanical property and biocompatibility. However, most of current HAp
      coatings lack coating/substrate interfacial strength, and/or biocompatibility.
      The cell-tissue attachment is affected by the degraded biocompatibility due to
      decomposition of HAp during high temperature processing. In this article, an
      innovative method, transmission laser coating (TLC), is investigated to coat HAp
      on Ti substrate with low temperature processing. This process enhances the
      HAp/Metal interfacial property of current coatings, while maintaining good
      biocompatibility. Experiments are conducted using a continuous neodymium-doped
      yttrium aluminium garnet (Nd-YAG) laser. Multiphysics simulation is conducted to
      simulate the temperature distribution in coatings and substrates during TLC
      processing. X-ray energy dispersion spectrum is used to measure the chemical
      composition of HAp coatings after TLC process. Pull-out tests are conducted to
      measure the interfacial strength between the HAp coating and Ti substrate. Cell
      culture study is conducted to qualitatively evaluate the biocompatibility after
      TLC of HAp particles. These results show that TLC processing will open new ways
      of producing biocompatible bioceramic coatings with controlled thickness, and at
      low processing temperature.

PMID- 19165794
TI  - Initial investigation of novel human-like collagen/chitosan scaffold for vascular
      tissue engineering.
AB  - With the increasing occurrence of vascular diseases and poor long-term patency
      rates of current small diameter vascular grafts, it becomes urgent to pursuit
      biomaterial as scaffold to mimic blood vessel morphologically and mechanically.
      In this study, novel human-like collagen (HLC, produced by recombinant E.
      coli)/chitosan tubular scaffolds were fabricated by cross-linking and freeze
      drying process. The scaffolds were characterized by scanning electron microscope
      (SEM), X-ray photoelectron spectroscopy (XPS), and tensile test, respectively.
      Human venous fibroblasts were expanded and seeded onto the scaffolds in the
      density of 1 x 10(5) cells/cm(2). After a 15-day culture under static conditions,
      the cell-polymer constructs were observed using SEM, confocal laser scanning
      microscopy (CLSM), histological examination, and biochemical assays for cell
      proliferation and extracellular matrix production (collagen and
      glycosaminoglycans). Furthermore, the scaffolds were implanted into rabbits'
      livers to evaluate their biocompatibility. The results indicated that
      HLC/chitosan tubular scaffolds (1) exhibited interconnected porous structure; (2)
      achieved the desirable levels of pliability (elastic up to 30% strain) and stress
      of 300 +/- 16 kPa; (3) were capable of enhancing cell adhesion and proliferation
      and ECM secretion; (4) showed superior biocompatibility. This study suggested the
      feasibility of HLC/chitosan composite as a promising candidate scaffold for blood
      vessel tissue engineering.

PMID- 19165796
TI  - Different apoptosis modalities in periprosthetic membranes.
AB  - This study reports on an investigation into apoptotic and proliferation signals
      in leukocyte and membrane fibroblasts in periprosthetic membranes collected
      during revision surgery for loosened total hip joint arthroplasty. Cementless and
      cemented prosthesis were studied under both aseptic and septic conditions.
      Fluorescence colocalization immunohistochemistry and colorimetric
      immunohistochemistry were used to investigate cell death signals. In aseptic
      cementless prosthesis macrophages and membrane fibroblasts show high bax signal,
      implying the occurrence of toxic/oxidative cell death caused by the debris of
      titanium alloy metal implant. Instead in aseptic cemented prosthesis only a
      moderate number of apoptotic leukocytes were observed, whilst the fibroblasts
      were affected by a diffuse apoptotic-like cell death, the Co-Cr ions debris
      released from cemented stem, may be at basis of apoptotic cell death induction.
      Furthermore cement debris is recognized to induce macrophages to produce
      cytokine, that may be responsible for the cell death observed and implant
      failure. The septic environment seems to protect leukocytes cell death. Septic
      cementless prosthesis showed only a few apoptotic leukocytes, instead fibroblasts
      remain affected by cell death signals. Similarly in septic cemented prosthesis,
      scanty apoptotic leukocytes were detected, whereas membrane fibroblasts showed an
      increase in proliferation index (Ki-67) along with caspase-3 activation. These
      findings indicate some kind of caspase-3 involvement in tissue proliferation,
      rather than in cell death pathway. Apoptotic periprosthetic sites have been
      interpreted as signs of inflammation resolution and normal tissue turnover.
      Nevertheless apoptosis may also be a sign of cell renewal associated to tissue
      proliferation.

PMID- 19165795
TI  - Fibrin-based tissue engineering scaffolds enhance neural fiber sprouting and
      delay the accumulation of reactive astrocytes at the lesion in a subacute model
      of spinal cord injury.
AB  - The purpose of this study was to evaluate the effects of fibrin scaffolds on
      subacute rat spinal cord injury (SCI). Long-Evans rats were anesthetized and
      underwent a dorsal hemisection injury; two weeks later, the injury site was re
      exposed, scar tissue was removed, and a fibrin scaffold was implanted into the
      wound site. An effective method for fibrin scaffold implantation following
      subacute SCI was investigated based on the presence of fibrin within the lesion
      site and morphological analysis 1 week after implantation. Prepolymerized fibrin
      scaffolds were found to be present within the lesion site 1 week after treatment
      and were used for the remainder of the study. Fibrin scaffolds were then
      implanted for 2 and 4 weeks, after which spinal cords were harvested and
      evaluated using markers for neurons, astrocytes, and chondroitin sulfate
      proteoglycans. Compared with untreated control, the fibrin-treated group had
      significantly higher levels of neural fiber staining in the lesion site at 2 and
      4 weeks after treatment, and the accumulation of glial fibrillary acidic protein
      (GFAP) positive reactive astrocytes surrounding the lesion was delayed. These
      results show that fibrin is conducive to regeneration and cellular migration and
      illustrate the advantage of using fibrin as a scaffold for drug delivery and cell
      based therapies for SCI.

PMID- 19165797
TI  - Enhancing annulus fibrosus tissue formation in porous silk scaffolds.
AB  - There is presently no optimal treatment for patients with chronic back pain as a
      result of degenerative disc disease. Tissue engineering, an annulus fibrosus (AF)
      construct suitable to repair the damaged AF, is one novel approach to the
      treatment of this disease. We have previously demonstrated that porous silk
      scaffolds can support AF cell attachment and extracellular matrix accumulation;
      however, tissue infiltration and matrix accumulation was not optimal. The purpose
      of this study was to determine whether the dynamic culture of AF cells seeded
      into larger average pore size silk scaffolds would improve tissue formation. AF
      cells were isolated from bovine caudal discs and seeded into porous silk
      scaffolds and grown in either dynamic or static flow conditions. The cell-seeded
      scaffolds were grown for up to 4 weeks and evaluated for cell attachment, gene
      expression, histological appearance, and matrix accumulation. Dynamic culture
      improved AF tissue formation as the tissue was more cellular and contained
      significantly more matrix than that formed in static culture. Spatial
      distribution of tissue was comparable for static and dynamic culture. Varying
      scaffold pore sizes (200-, 600-, and 1000-microm pore size) demonstrated that an
      average pore size of 600 microm resulted in the most uniform tissue distribution
      with the greatest amount of type I collagen. Our study suggests that dynamic flow
      conditions and scaffold pore size can affect the formation of engineered AF
      tissue.

PMID- 19165798
TI  - The effect of scaffold architecture on properties of direct 3D fiber deposition
      of porous Ti6Al4V for orthopedic implants.
AB  - 3D porous Ti6Al4V scaffolds were directly fabricated by a rapid prototyping
      technology, 3D fiber deposition (3DF). In this study, scaffolds with different
      structures were fabricated by changing fiber spacing and fiber orientation. The
      influence of different architectures on mechanical properties and permeability of
      the scaffold were investigated. Mechanical analysis revealed that compressive
      strength and E-modulus increase with decreasing the porosity. Permeability
      measurements showed that not only the total porosity but also the porous
      structure can influence the permeability. 3DF was found to provide good control
      and reproducibility of the desired degree of porosity and the 3D structure.
      Results of this study demonstrate that the 3DF of Ti6Al4V give us flexibility and
      versatility to fabricate and improve scaffolds to better mimic the architecture
      and properties of natural bone and meet the requirements of bone graft
      substitutes and orthopedic and dental implants.

PMID- 19165799
TI  - Bioactivation of collagen matrices through sustained VEGF release from PLGA
      microspheres.
AB  - The success of any tissue engineering implant relies upon prompt vascularization
      of the cellular construct and, hence, on the ability of the scaffold to broadcast
      specific activation of host endothelium and guide vessel ingrowth. Vascular
      endothelial growth factor (VEGF) is a potent angiogenic stimulator, and if
      released in a controlled manner it may enhance and guide scaffold
      vascularization. Therefore, the aim of this work was to realize a scaffold with
      integrated depots able to release VEGF in a controlled rate and assess the
      ability of this scaffold to promote angiogenesis. VEGF-loaded poly(lactide-co
      glycolide) (PLGA) microspheres were produced and included in a collagen scaffold.
      The release of VEGF from microspheres was tailored to be sustained over several
      weeks and occurred at a rate of approximately 0.6 ng/day per mg of microspheres.
      It was found that collagen scaffolds bioactivated with VEGF-loaded microspheres
      strongly enhanced endothelial cell activation and vascular sprouting both in
      vitro and in vivo as compared with a collagen scaffold bioactivated with free
      VEGF. This report demonstrates that by finely tuning VEGF release rate within a
      polymeric scaffold, sprouting of angiogenic vessels can be guided within the
      scaffolds interstices as well as broadcasted from the host tissues.

PMID- 19165800
TI  - Resveratrol attenuates 1,2-dimethylhydrazine (DMH) induced glycoconjugate
      abnormalities during various stages of colon carcinogenesis.
AB  - Although a myriad of health promoting effects has been attributed to resveratrol
      (Res) (3,5,4'-trihydroxy-trans-stilbene), a phytoalexin, the most interesting is
      its anticancer property. The aim of this work was to elucidate the effectiveness
      of Res against cellular transformation (glycoconjugate alterations) initiated by
      1,2-dimethylhydrazine (DMH), a colon specific carcinogen. Group 1 were control
      rats, group 2 were control rats that received Res (8 mg/kg body weight orally
      every day), rats in groups 3-6 were treated weekly with DMH (20 mg/kg body
      weight, subcutaneously x 15 times). In addition, groups 4-6 received Res (as in
      group 2) in three dietary regimens: initiation (I), post-initiation (PI) and
      entire period (EP). At the end of the 30 week experimental period in DMH alone
      exposed rats, altered levels of glycoconjugates (total hexoses, fucose,
      hexosamine and sialic acid) were observed in liver, intestine and colon tissues.
      Of the three dietary regimens of Res, the entire period supplementation
      significantly (p < 0.01) modulated the levels of glycoconjugates and reduced the
      incidence of adenoma and adenocarcinoma. These findings suggest that Res may
      extend its chemopreventive effect by restoring the alteration in glycoconjugates
      that are thought to be involved in the colonic malignant transformation process
      in this experimental model.

PMID- 19165801
TI  - Cardioprotective effect of sasanquasaponin preconditioning via bradykinin-NO
      pathway in isolated rat heart.
AB  - Sasanquasaponin (SQS) is an effective component of Camellia oleifera Abel. This
      study was designed to investigate the cardioprotective effect of SQS against
      ischemia-reperfusion (I/R) injury and the possible mechanism in isolated rat
      hearts. These hearts were pretreated by SQS only or SQS and HOE140 in different
      groups, and then subjected to I/R injury. Hemodynamic parameters, oxidative
      injury, and NO level were measured. The results showed that SQS preconditioning
      could decrease the incidences of arrhythmias and improve the heart functions. In
      addition, SQS preconditioning could protect isolated I/R injured heart against
      lipid peroxidation, as evidenced by increases in SOD and GSH-Px activity, and by
      decreases in contents of MDA, ROS generation. However, HOE140 treatment reversed
      all these indexes. NO production was significantly decreased after a treatment
      with HOE140. So we can propose that SQS preconditioning could induce the
      cardioprotective effects and the possible mechanism was that the activation of
      bradykinin-NO system by SQS preconditioning had an inhibition effect on ROS
      generation in isolated heart.

PMID- 19165802
TI  - Reproductive and hormonal risk factors for postmenopausal luminal, HER-2
      overexpressing, and triple-negative breast cancer.

PMID- 19165804
TI  - The clinical diversity of postchemotherapy germ cell teratoma.

PMID- 19165805
TI  - Survival of patients in a Phase 1 Clinic: the M. D. Anderson Cancer Center
      experience.
AB  - BACKGROUND: Patients with advanced malignancies for whom standard therapy is
      ineffective may participate in phase 1 trials. To gain a better understanding of
      the clinical features that could influence benefit versus risk, the authors of
      this report assessed prognostic factors and survival for patients who were
      referred to a phase 1 clinic focused primarily on targeted agents. METHODS: The
      medical records of 200 sequential patients who presented to the Phase 1 Clinic at
      The University of Texas M. D. Anderson Cancer Center were reviewed, and their
      characteristics and survival were analyzed. RESULTS: The median patient age was
      58 years (range, 12-85 years), and 57% of patients were men. The median number of
      prior therapies was 4. Of 200 patients, 182 were treated on at least 1 phase 1
      clinical trial. The median follow-up of surviving patients was 21 months, and the
      median overall survival was 9 months (95% confidence interval [CI], 7.4-10.8). In
      univariate analysis, the factors that predicted shorter survival were primary
      tumor in the gastrointestinal tract; a history of thrombosis, liver metastases,
      and elevated levels of serum lactate dehydrogenase; platelet count; carbohydrate
      antigen 9 (Ca19-9) and Ca-125 levels; aspartate aminotransferase levels, and
      alkaline phosphatase levels (P < .05 for each). In multivariate analysis,
      independent factors that predicted shorter survival were a history of
      thromboembolism (hazard ratio [HR], 2.38; 95% CI, 1.29-4.39; P = .005), platelets
      >or=440 x 10(9)/L (HR, 1.72; 95% CI, 1.12-2.65; P = .014), and the presence of
      liver metastases (HR, 1.51; 95% CI, 1.09-2.09; P = .013). CONCLUSIONS: Patients
      who were referred to phase 1 studies had a short median survival (9 months).
      Patients with thrombocytosis, liver metastases, and a history of thromboembolism
      had worse outcomes. A prognostic score is proposed.

PMID- 19165806
TI  - Low positive predictive value of the oral brush biopsy in detecting dysplastic
      oral lesions.
AB  - BACKGROUND: The authors evaluated the effectiveness of the oral brush biopsy
      technique as a diagnostic tool in detecting dysplastic oral lesions. METHODS: In
      this cross-sectional study, pathologic reports (n = 152) from the scalpel
      biopsies (tissue samples) in patients who previously tested either "positive" (n
      = 3) or "atypical" (n = 149) for dysplasia by brush biopsy (OralCDx) were
      evaluated. Information on the age and sex of the patient, the site of the lesion,
      the brush biopsy results, and the histopathologic diagnosis of the scalpel biopsy
      was collected. The positive predictive values (PPVs) for "abnormal," "atypical,"
      and "positive" brush biopsies were determined. RESULTS: Overall, the PPV of an
      abnormal brush biopsy was only 7.9% (95% confidence interval [CI], 4.2%-13.4%),
      and the PPV of an "atypical" brush biopsy was 7.4% (95% CI, 3.7%-12.8%). Of the 3
      positive brush biopsies, only 1 was identified as dysplastic. The proportion of
      false-positive biopsy results was as high as 92.1% (95% CI, 86.6%-95.9%).
      CONCLUSIONS: The OralCDx technique overestimated dysplastic lesions and produced
      a high number of false-positive results.

PMID- 19165807
TI  - Routine perioperative chemotherapy instillation with initial bladder tumor
      resection: a reconsideration of economic benefits.
AB  - BACKGROUND: Level-1 evidence has demonstrated decreased recurrence of low-grade
      bladder tumors when initial transurethral resection (TUR) is followed by
      perioperative instillation (PI) of chemotherapy. A meta-analysis determined that
      the number needed to treat (NNT) was 8.5 patients to prevent 1 recurrence. No
      benefit was demonstrated for tumors classified as T0, tumor in situ, or T2; thus,
      patients with those tumors were excluded from the analysis, which potentially may
      have resulted in underestimating the true NNT. Economic benefits were suggested,
      but cost calculations were not presented. The objectives of the current analysis
      were to recalculate the NNT considering patients who previously were excluded and
      to examine the economic implications based on various management alternatives for
      tumor recurrence. METHODS: For each study that was included in the current meta
      analysis, the number of patients excluded because of 'inappropriate' pathology
      results was determined. A potentially more accurate NNT was calculated, and
      pertinent Medicare reimbursements were obtained to estimate costs. RESULTS: The
      added cost for 8.5 patients who underwent inpatient TUR to receive PI was $1711.
      Inpatient TUR ($7025) was extremely costly compared with hospital outpatient TUR
      ($2666), ambulatory surgery center TUR ($2113), and physician office fulguration
      ($1167). Although the inclusion of patients who previously were excluded resulted
      in a recalculated NNT of 9.6 patients, the authors used a more conservative NNT
      if 8.5 patients to estimate the economic impact of the 'best-case scenario.'
      CONCLUSIONS: Routine PI significantly lowered the overall cost if recurrences
      were managed in the inpatient setting, but these benefits were offset mostly or
      completely by outpatient management in the United States. Thus, the authors
      concluded that the decision to use routine PI of chemotherapy should be based on
      clinical effects and not on presumed economic benefits.

PMID- 19165808
TI  - The changing face of phase 1 cancer clinical trials: new challenges in study
      requirements.
AB  - Phase 1 studies in cancer have changed in recent years. Now, with the advent of
      new, less toxic, targeted agents, more patients may be candidates for new drug
      studies earlier in the course of their disease. It is to the advantage of the
      members of the oncology community to know more regarding the details and
      requirements for participation in early-phase clinical trials so they can
      advocate for their patients and help them decide when such trials may be an
      appropriate choice. To examine the work intensity of early phase cancer clinical
      trials, the authors of this report compared the study requirements of phase 1 and
      2 protocols. Five parameters were studied as a surrogate of study complexity-the
      number of physical examinations, vital sign determinations, electrocardiograms
      (ECGs), nonpharmacokinetic laboratory tests, and pharmacokinetic (PK) sampling-in
      the first 4 weeks of protocol in 90 studies (49 phase 1 studies and 41 phase 2
      studies). From July 2004 through March 2007, there were 49 phase 1 trials in the
      phase 1 Program, 9 phase 2 studies that were conducted by physicians appointed in
      that program, and 32 phase 2 trials with accessible data in the Department of
      Thoracic/Head & Neck Medical Oncology. In the phase 1 trials versus the phase 2
      trials, there were significantly more (P < .05) physical examinations (mean +/-
      standard error, 3.16 +/- 0.24 vs 2.22 +/- 0.13), vital sign determinations (5.63
      +/- 0.61 vs 2.80 +/- 0.26), ECGs (4.36 +/- 1.16 vs 0.80 +/- 0.17),
      nonpharmacokinetic laboratory tests (18.08 +/- 1.31 vs 10.12 +/- 0.65), and PK
      sampling (15.14 +/- 1.79 vs 1.02 +/- 0.53). These values also differed
      significantly (P < .005 for each) when the median values were compared in
      nonparametric tests. Although both phase 1 and phase 2 trials had substantial
      study requirements, those for the phase 1 studies were significantly higher. The
      successful conduct of early-phase clinical trials requires significant research
      infrastructure.

PMID- 19165809
TI  - Adult attachment as mediator between recollections of childhood and satisfaction
      with life.
AB  - In accordance with attachment theory, the present study investigates whether
      internal working models of attachment mediated the association between childhood
      memories and satisfaction about life in adulthood. A convenient sample of 437
      participants completed questionnaires assessing a broad range of childhood
      memories, working models of attachment and life satisfaction. After controlling
      for demographics, relational status and living condition, Baron and Kenny's
      mediation criteria were met for the association between memories about childhood,
      adult attachment and life satisfaction. That is, family warmth and harmony and
      parental support were associated with attachment security while parental
      rejection and adverse childhood events (e.g., abuse, parental psychopathology)
      were associated with an insecure attachment style. More securely attached
      individuals were in turn more satisfied about their current life than insecurely
      attached individuals. Sobel test confirmed these findings. These finding are in
      accordance with attachment theory and highlight the importance of this theory for
      understanding how early childhood experiences may impact adult life.

PMID- 19165810
TI  - Attachment and interpersonal distress: examining the relationship between
      attachment styles and interpersonal problems in a clinical population.
AB  - The present study examined the relationship between self-perceived attachment
      styles and interpersonal problems. Specifically, we utilized a clinical sample
      from an outpatient university-based community clinic who completed the
      Experiences in Close Relationships Scale-Revised, the Relationship Questionnaire
      and Inventory of Interpersonal Problems Circumplex Scales (IIP-64) as part of a
      psychological assessment process. The results showed a significant positive
      correlation between the IIP-64 total score and both attachment anxiety and
      attachment avoidance. Findings revealed significant negative relationships
      between a secure attachment and the dominant, vindictive, cold, socially
      inhibited and non-assertive subscales of the IIP-64. Findings also revealed a
      significant positive relationship between a fearful attachment and the dominant,
      vindictive, cold, socially inhibited and non-assertive subscales of the IIP-64.
      Finally, results showed a significant relationship between a dismissive
      attachment and the dominant subscale of the IIP-64.

PMID- 19165811
TI  - Low molecular weight proteins in urines from healthy subjects as well as
      diabetic, nephropathic and diabetic-nephropathic patients: a MALDI study.
AB  - Urine samples from healthy subjects as well as diabetic, nephropathic and
      diabetic-nephropathic patients were analyzed by matrix assisted laser
      desorption/ionization (MALDI) mass spectrometry in order to establish evidence of
      some possible differences in the peptide profile related to the pathological
      states. Multivariate analysis suggested the possibility of a distinction among
      the considered groups of patients. Some differences have been found, in
      particular, in the relative abundances of three ions at m/z 1912, 1219 and 2049.
      For these reasons, further investigation was carried out by MALDI/TOF/TOF to
      determine the sequence of these peptides and, consequently, to individuate their
      possible origin. By this approach, the peptide at m/z 1912 was found to originate
      from uromodulin, and its lower expression in the case of nephropathy can be well
      related to the pathological condition. Ions at m/z 2049 and 1219 originate from
      the collagen alpha-1(I) chain precursor and from the collagen alpha-5 (IV) chain
      precursor, respectively, and, also in this case, their different expressions can
      be related to the pathologies under investigation. The obtained data seem to
      indicate that urine is an interesting biological fluid to investigate on the
      peptide profile and to obtain, consequently, information on the dismetabolism
      activated by specific pathologies.

PMID- 19165812
TI  - I405V and TaqIB polymorphisms of the cholesteryl ester transfer protein and their
      relation to serum lipid and lipoprotein levels in a Turkish population.
AB  - Cholesteryl ester transfer protein (CETP) plays a central role in high-density
      lipoprotein (HDL) metabolism. Genetic polymorphisms of the CETP gene can
      influence levels of serum lipoproteins. It has been reported that mean HDL
      cholesterol (HDL-C) concentrations are low in Turkish population. Thus, we
      investigated the frequencies of the common I405V and TaqIB polymorphisms of the
      CETP gene and their relation to serum lipid and lipoprotein levels in a Turkish
      population. The variant allele frequencies of I405V and TaqIB polymorphisms of
      the CETP gene were found to be 0.38 and 0.46, respectively and similar to some of
      the European populations. Subjects for the VV genotype of I405V polymorphism had
      higher HDL-C levels than did II subjects. The covariance analysis showed that
      gender and triglyceride (TG) levels have an effect on the association of HDL-C
      and I405V polymorphism. In conclusion, our results indicate that I405V
      polymorphism may affect the HDL-C levels in Turkish population. The association
      of this polymorphism and HDL-C levels could be modified by other factors, such as
      gender and TG levels.

PMID- 19165813
TI  - Matrix metalloproteinase-2 and -9 activities in human keloids, hypertrophic and
      atrophic scars: a pilot study.
AB  - Proteolytic degradation of extracellular matrix is one of the principal features
      of cutaneous wound healing but little is known about the activities of
      gelatinases; matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9
      (MMP-9) on abnormal scar formation. The aim of this study is to determine
      collagen levels and the gelatinase activities in tissue from hypertrophic scars,
      atrophic scars, keloids and donor skin in 36 patients and 14 donors. Gelatinase
      levels (proenzyme + active enzyme) were determined by ELISA and their activities
      by gelatin zymography. MMP-9 activity was undetectable in gelatin zymography
      analysis. Pro-MMP-2 levels (median) were highest in normal skin group 53.58
      (36.40-75.11) OD microg(-1) protein, while active MMP-2 levels were highest in
      keloid group 52.53 (42.47-61.51) OD microg(-1) protein. The active/pro ratio was
      the highest in keloid group 0.97 followed by hypertrophic scar, normal skin and
      atrophic scar groups 0.69 > 0.54 > 0.48, respectively. According to results of
      our study, the two-phase theory of the duration of hypertrophic scar and keloid
      formation can be supported by the data of tissue collagen and gelatinase
      analysis. This study is the first to relate scar formation relationship in regard
      to gelatinase activation ratio in a keloid, hypertrophic and atrophic scar
      patient group which is chosen appropriate in age and sex.

PMID- 19165814
TI  - Psychometric validity of the Cochlear Implant Function Index (CIFI): a quality of
      life assessment tool for adult cochlear implant users.
AB  - OBJECTIVE: The Cochlear Implant Function Index (CIFI) is created to assess adult
      cochlear implant (CI) auditory effectiveness in real world situations. Our
      objective is to evaluate the CIFI as a reliable psychometric tool to assess 1)
      reliance on visual assistance, 2) telephone use, 3) communication at work, 4)
      'hearing' in noise, 5) in groups, and 6) in large room settings. STUDY DESIGN:
      Based upon Guttman scaling properties, the CIFI elicits implanted respondent's
      functional level with auditory independence from Level 1 (still requiring
      signing) to level 4 (without any help beyond CI). A blinded, retrospective
      questionnaire is anonymously answered by cochlear implant recipients. SETTING: CI
      centers of tertiary care medical centers, CI support group, and an interactive
      web page of a hearing and speech center in a large metropolitan region. SUBJECTS:
      245 respondents from a varied adult CI population implanted for one month to 19
      years prior to answering the questionnaire. INTERVENTION: An assessment tool of
      CI function. MAIN OUTCOME MEASURE: A coefficient of reproducibility (CR) for the
      Guttman scale format equal or greater than 0.90, indicating good scalability.
      RESULTS: CR in the CIFI was above 0.90. Effective scalability and mean scores
      from 2.5 to 3.5 for the six areas examined (1.00-4.00) were achieved. CONCLUSION:
      The psychometric properties of this user friendly survey demonstrate consistently
      good scalability. Based on these findings, the CIFI provides a validated tool
      that can be used for systematic comparisons between groups of patients or for
      follow-up outcomes in patients who use cochlear implants. Further study is
      indicated to correlate CIFI scores with sound and speech perception scores.

PMID- 19165816
TI  - Development of extraction protocols to improve the yield for fetal RNA in
      maternal plasma.

PMID- 19165817
TI  - Study by ESI-FTICRMS and ESI-FTICRMS(n) of zinc and cadmium thiophenolate
      complexes used as precursors for the synthesis of II-VI nanosemiconductors.
AB  - [M(4)(SC(6)H(5))(10)][(CH(3))N](2), [M(10)L(4)(SC(6)H(5))(16)][(CH(3))N](4) and
      [Cd(17)S(4)(SC(6)H(5))(28)][(CH(3))N](2)(M = Cd or Zn, and L = S or Se) zinc and
      cadmium thiophenolates have been studied by electrospray ionization (ESI) Fourier
      transform ion cyclotron resonance (FTICR) mass spectrometry (ESI-FTICRMS) and
      tandem ESI-FTICRMS (ESI-FTICRMS(n)). ESI-FTICRMS demonstrated its ability to
      characterize and study such compounds, which may be used as precursors of II-VI
      nanomaterials. The obtained mass spectrum has been found to be highly relevant of
      the investigated thiophenolate and the fragmentation behavior of some of the
      detected ions is indicative of its stability. More specifically, it has been
      demonstrated that ESI in-source activation or fragmentation experiments conducted
      in the Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) cell
      induced the formation of a very stable entity, which corresponds to the general
      formula M(4)L(4) (M = Zn or Cd and L = S or Se). The elimination of SC(6)H(5)(-)
      and/or M(SC(6)H(5))(2) moieties by various activation processes from the studied
      thiophenolates led systematically to this structure.

PMID- 19165818
TI  - On the inter-instrument and inter-laboratory transferability of a tandem mass
      spectral reference library: 1. Results of an Austrian multicenter study.
AB  - The inter-instrument and inter-laboratory transferability of a tandem mass
      spectral reference library originally built on a quadrupole-quadrupole-time-of
      flight instrument was examined. The library consisted of 3759 MS/MS spectra
      collected from 402 reference compounds applying several different collision
      energy values for fragmentation. In the course of the multicenter study, 22 test
      compounds were sent to three different laboratories, where 418 tandem mass
      spectra were acquired using four different instruments from two manufacturers.
      The study covered the following types of tandem mass spectrometers: quadrupole
      quadrupole-time-of-flight, quadrupole-quadrupole-linear ion trap, quadrupole
      quadrupole-quadrupole, and linear ion trap-Fourier transform ion cyclotron
      resonance mass spectrometer. In each participating laboratory, optimized
      instrumental parameters were gathered solely from routinely applied workflows. No
      standardization procedure was applied to increase the inter-instrument
      comparability of MS/MS spectra. The acquired tandem mass spectra were matched
      against the established reference library using a sophisticated matching
      algorithm, which is presented in detail in a companion paper. Correct answers,
      meaning that the correct compound was retrieved as top hit, were obtained in
      98.1% of cases. For the remaining 1.9% of spectra, the correct compound was
      matched at second rank. The observed high percentage of correct assignments
      clearly suggests that the developed mass spectral library search approach is to a
      large extent platform independent.

PMID- 19165819
TI  - The role of peptides and proteins in melanoidin formation.
AB  - High-molecular-weight (HMW) coloured compounds called melanoidins are widely
      distributed, particularly in foods. It has been proposed that they originate
      through the Maillard reaction, a non-enzymatic browning reaction, due to the
      interaction between protein or peptide amino groups and carbohydrates. The
      melanoidin structure is not definitively known, and they have been generally
      defined as HMW nitrogen-containing brown polymers.In order to gain information on
      the nature of melanoidins, a simple in vitro model was chosen to investigate the
      products of the reactions between sugars and peptide/proteins. This approach
      would elucidate whether melanoidin formation is due to the binding of different
      sugar units to a peptide/protein or vice versa. With this aim, the reactivity of
      two different peptides, EPK177 and physalaemin, and a low-molecular-weight (LMW)
      protein, lysozyme, was tested towards different saccharides (glucose, maltotriose
      (MT), maltopentaose and dextran 1000) in aqueous solutions at different
      temperatures. The incubation mixtures were analysed at different reaction times
      by MALDI/MS. Furthermore, in order to verify the possible role of sugar pyrolysis
      products in melanoidin formation, the products arising from the thermal treatment
      at 200 degrees C of MT were incubated with lysozyme, and the reaction products
      were analysed by the same MS approach.The obtained results allowed the
      establishment of some general views: melanoidins cannot simply originate by
      reactions of sugar moieties with proteins. In fact, the reaction easily occurs,
      but it does not lead to any coloured product, as melanoidins have been described
      to be; melanoidins cannot originate from the thermal degradation products of
      glycated proteins. In fact, the thermal treatment of glycated lysozyme leads to a
      severe degradation of the protein with the formation of LMW species, far from the
      view of melanoidins as HMW compounds; experimental evidence has been gained on
      the melanoidin formation through reaction of intact protein with the pyrolysis
      products of MT. This hypothesis has been supported either from MALDI measurements
      or from spectroscopic data that show an absorption band in the range 300-600 nm,
      typical of melanoidins.

PMID- 19165820
TI  - Effects of static magnetic field on magnetosome formation and expression of mamA,
      mms13, mms6 and magA in Magnetospirillum magneticum AMB-1.
AB  - Magnetotactic bacteria produce nanometer-size intracellular magnetic crystals.
      The superior crystalline and magnetic properties of magnetosomes have been
      attracting much interest in medical applications. To investigate effects of
      intense static magnetic field on magnetosome formation in Magnetospirillum
      magneticum AMB-1, cultures inoculated with either magnetic or non-magnetic pre
      cultures were incubated under 0.2 T static magnetic field or geomagnetic field.
      The results showed that static magnetic field could impair the cellular growth
      and raise C(mag) values of the cultures, which means that the percentage of
      magnetosome-containing bacteria was increased. Static magnetic field exposure
      also caused an increased number of magnetic particles per cell, which could
      contribute to the increased cellular magnetism. The iron depletion in medium was
      slightly increased after static magnetic field exposure. The linearity of
      magnetosome chain was also affected by static magnetic field. Moreover, the
      applied intense magnetic field up-regulated mamA, mms13, magA expression when
      cultures were inoculated with magnetic cells, and mms13 expression in cultures
      inoculated with non-magnetic cells. The results implied that the interaction of
      the magnetic field created by magnetosomes in AMB-1 was affected by the imposed
      magnetic field. The applied static magnetic field could affect the formation of
      magnetic crystals and the arrangement of the neighboring magnetosome.

PMID- 19165821
TI  - Cytoprotective effects of the lipoidic-liquiform pro-vitamin C tetra-isopalmitoyl
      ascorbate (VC-IP) against ultraviolet-A ray-induced injuries in human skin cells
      together with collagen retention, MMP inhibition and p53 gene repression.
AB  - Irradiation with ultraviolet-A (UVA) ray at doses of 20-100 J/cm(2) diminished
      the cell viability of human keratinocytes HaCaT and human melanoma cells HMV-II,
      both of which were protected by pre-irradiational administration with the
      ascorbic acid (Asc) derivative, VC-IP (2,3,5,6-O-tetra-2'-hexyldecanoyl-L
      ascorbic acid; vitamin C-isopalmityl tetraester), which is the first lipoidic
      liquiform pro-vitamin C by itself that is materialized by esterization of all
      four intramolecular hydroxyl groups of an Asc molecule with branched chain fatty
      groups, resulting in molecular fluidity higher than that of the corresponding
      straight chains. Irradiation with UVA to HaCaT keratinocytes was shown to cause
      the formation of 8-hydroxydeoxyguanosine (8-OHdG), translocation of
      phosphatidylserine in the inner layer into the outer layer of cell membrane, and
      lowering of a mitochondrial membrane potential, all of which were repressed by
      pre-irradiational administration with VC-IP. Expression of p53 gene, another
      hallmark of UV-induced DNA damages, was promoted by UVA irradiation to the
      keratinocytes but also repressed by VC-IP. Administration with VC-IP of 10-50
      microM to human fibroblasts NHDF achieved the enhancement of collagen synthesis,
      repression of matrix metalloprotease-2/9 activity, and increasing of
      intracellular Asc contents more markedly than that with Asc itself of the same
      concentrations. Thus UVA-induced diverse harmful effects could be prevented by VC
      IP, which was suggested to ensue intrinsically from the persistent enrichment of
      intracellular Asc, through esterolytic conversion of VC-IP to a free-form Asc
      molecule, resulting in relief to UVA-caused oxidative stress.

PMID- 19165822
TI  - Influence of a self-assembling peptide, RADA16, compared with collagen I and
      Matrigel on the malignant phenotype of human breast-cancer cells in 3D cultures
      and in vivo.
AB  - Cancer-cell phenotype is not only the result of malignant progression, but also
      dependent on the microenvironment surrounding them, including influences from the
      extracellular matrix and its structural properties. We have investigated the
      influence of the nanofiber matrix of the self-assembling peptide, RADA16, in
      comparison with collagen I and Matrigel on the malignant phenotype of the human
      breast-cancer cell, MDA-MB-231, in 3D cultures, including the morphology,
      survival, proliferation rate, migration potential and the effect of these
      matrices on the malignancy of the cancer cells in vivo. Our data indicate that
      these tumor cells change their morphology in response to the different 3D matrix
      in vitro cultures and the RADA16 self-assembling peptide scaffold mimics an
      extracellular matrix and could effectively reduce the malignant phenotype of the
      tumor cells in vitro and in vivo.

PMID- 19165823
TI  - Dependence of protein recognition of temperature-sensitive imprinted hydrogels on
      preparation temperature.
AB  - Temperature-sensitive imprinted and non-imprinted hydrogels composed of N
      isopropylacrylamide (NIPA) and 2-acrylamido-2-methyl-propanosulfonic acid (AMPS)
      have been prepared by free-radical crosslinking copolymerization in aqueous
      solution at three different temperatures: 10 degrees C (below the lower critical
      solution temperature, LCST), 33 degrees C (at the LCST), and 40 degrees C (above
      the LCST). Myoglobin (Mb, MW 17 kDa) is used as the template biomolecule. The
      effects of the initial concentration and adsorption time over the Mb adsorption
      capacity of the hydrogels have been analyzed and found to be strongly dependent
      on the preparation temperature (T(prep)). The maximum Mb adsorption for the
      imprinted hydrogel prepared at 10 degrees C is 97.40 +/- 2.35 mg Mb x g(-1) dry
      gel in 0.32 mg x mL(-1) Mb solution at 22 degrees C. Moreover, batch adsorption
      equilibrium and selectivity studies have been performed using a reference
      molecule, hemoglobin (Hb, MW 65 kDa). The imprinted hydrogels have a 2.8-3.3
      times higher adsorption capacity for Mb than the non-imprinted hydrogels prepared
      at the same T(prep)s, and also have a 1.8-2.7 times higher selectivity for the
      imprinted molecule.

PMID- 19165824
TI  - Porous biodegradable scaffold: predetermined porosity by dissolution of
      poly(ester-anhydride) fibers from polyester matrix.
AB  - A novel selective leaching method for the porogenization of the biodegradable
      scaffolds was developed. Continuous, predetermined pore structure was prepared by
      dissolving fast eroding poly(epsilon-caprolactone)-based poly(ester-anhydride)
      fibers from the photo-crosslinked poly(epsilon-caprolactone) matrix. The porogen
      fibers dissolved in the phosphate buffer (pH 7.4, 37 degrees C) within a week,
      resulting in the porosity that replicated exactly the single fiber dimensions and
      the overall arrangement of the fibers. The amount of the porosity, estimated with
      micro-CT, corresponded with the initial amount of the fibers. The potential to
      include bioactive agents in the porogen fibers was demonstrated with the
      bioactive glass.

PMID- 19165825
TI  - The surface modification of hydroxyapatite nanoparticles by the ring opening
      polymerization of gamma-benzyl-l-glutamate N-carboxyanhydride.
AB  - The surface modification of hydroxyapatite (HA) nanoparticles by the ring opening
      polymerization (ROP) of gamma-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA) was
      proposed to prepare the poly(gamma-benzyl-L-glutamate) (PBLG)-grafted HA
      nanoparticles (PBLG-g-HA) for the first time. HA nanoparticles were firstly
      treated by 3-aminopropylthriethoxysilane (APS) and then the terminal amino groups
      of the modified HA particles initiated the ROP of BLG-NCA to obtain PBLG-g-HA.
      The process was monitored by XPS and FT-IR. The surface grafting amounts of PBLG
      on HA ranging from 12.1 to 43.1% were characterized by thermal gravimetric
      analysis (TGA). The powder X-ray diffraction (XRD) analysis confirmed that the
      ROP only underwent on the surface of HA nanoparticles without changing its bulk
      properties. The SEM measurement showed that the PBLG-g-HA hybrid could form an
      interpenetrating net structure in the self-assembly process. The PBLG-g-HA hybrid
      could maintain higher colloid stability than the pure HA nanoparticles. The in
      vitro cell cultures suggested the cell adhesion ability of PBLG-g-HA was much
      higher than that of pure HA.

PMID- 19165826
TI  - Absence of TGFbeta signaling in embryonic vascular smooth muscle leads to reduced
      lysyl oxidase expression, impaired elastogenesis, and aneurysm.
AB  - To address the requirement for TGFbeta signaling in the formation and maintenance
      of the vascular matrix, we employed lineage-specific mutation of the type II
      TGFbeta receptor gene (Tgfbr2) in vascular smooth muscle precursors in mice. In
      both neural crest- and mesoderm-derived smooth muscle, absence of TGFbeta
      receptor function resulted in a poorly organized vascular elastic matrix in late
      stage embryos which was prone to dilation and aneurysm. This defect represents a
      failure to initiate formation of the elastic matrix, rather than a failure to
      maintain a preexisting matrix. In mutant tissue, lysyl oxidase expression was
      substantially reduced, which may contribute to the observed pathology.

PMID- 19165827
TI  - A multifunctional reporter mouse line for Cre- and FLP-dependent lineage
      analysis.
AB  - The Cre/lox and FLP/FRT recombination systems have been used extensively for both
      conditional knockout and cell lineage analysis in mice. Here we report a new
      multifunctional Cre/FLP dual reporter allele (R26(NZG)) that exhibits strong and
      apparently ubiquitous marker expression in embryos and adults. The reporter
      construct, which is driven by the CAG promoter, was knocked into the ROSA26 locus
      providing an open chromatin domain for consistent expression and avoiding site-of
      integration effects often observed with transgenic reporters. R26(NZG) directs
      Cre-dependent nuclear-localized beta-galactosidase (beta-gal) expression, and can
      be converted into a Cre-dependent EGFP reporter (R26(NG)) by germline excision of
      the FRT-flanked nlslacZ cassette. Alternatively, germline excision of the floxed
      PGKNEO cassette in R26(NZG) generates an FLP-dependent EGFP reporter (R26(ZG))
      that expresses beta-gal in FLP-nonexpressing cells. Finally, by the simultaneous
      use of both Cre and FLP deleters, R26(NZG) allows lineage relationships to be
      interrogated with greater refinement than is possible with single recombinase
      reporter systems.

PMID- 19165828
TI  - Use of FOXJ1CreER2T mice for inducible deletion of embryonic node gene
      expression.
AB  - The ciliated cells of the node of the mouse embryo contribute to the
      establishment of left-right patterning via generation of leftward laminar fluid
      flow and initiation of a left-sided morphogen gradient. Here, we identify
      FOXJ1CreER(2T) mice in which expression of Cre recombinase is directed to
      ciliated node cells. The data demonstrate that foxj1 is expressed specifically in
      the node throughout the developmental window critical for left-right patterning.
      In transgenic embryos, Cre expression is detected by immunohistochemistry in
      ciliated cells of the node. Rosa26R reporter mice, in which expression of lacZ is
      activated only after Cre-mediated recombination, demonstrate strong and uniform
      labeling at the node when crossed with FOXJ1CreER(2T) mice. Cell labeling
      occurred as early as 0- to 2-somite stages, specifically within cells of the
      node, and recombination was highly efficient in response to tamoxifen.
      FOXJ1CreER(2T) transgenic mice represent a new genetic tool for the analysis of
      node-specific gene expression and will also be valuable in the study of node cell
      lineage and temporal cell fate mapping.

PMID- 19165830
TI  - An enhancement of coronary blood flow in a fetus with supraventricular
      tachycardia.

PMID- 19165829
TI  - A new mouse model for temporal- and tissue-specific control of extracellular
      superoxide dismutase.
AB  - The extracellular isoform of superoxide dismutase (EC-SOD, Sod3) plays a
      protective role against various diseases and injuries mediated by oxidative
      stress. To investigate the pathophysiological roles of EC-SOD, we generated
      tetracycline-inducible Sod3 transgenic mice and directed the tissue-specific
      expression of transgenes by crossing Sod3 transgenic mice with tissue-specific
      transactivator transgenics. Double transgenic mice with liver-specific expression
      of Sod3 showed increased EC-SOD levels predominantly in the plasma as the
      circulating form, whereas double transgenic mice with neuronal-specific
      expression expressed higher levels of EC-SOD in hippocampus and cortex with
      intact EC-SOD as the dominant form. EC-SOD protein levels also correlated well
      with increased SOD activities in double transgenic mice. In addition to enabling
      tissue-specific expression, the transgene expression can be quickly turned on and
      off by doxycycline supplementation in the mouse chow. This mouse model, thus,
      provides the flexibility for on-off control of transgene expression in multiple
      target tissues.

PMID- 19165831
TI  - Mutations in the mitochondrial cytochrome b of Tetranychus urticae Koch (Acari:
      Tetranychidae) confer cross-resistance between bifenazate and acequinocyl.
AB  - BACKGROUND: Resistance of Tetranychus urticae Koch to bifenazate was recently
      linked with mutations in the mitochondrial cytochrome b Q(o) pocket, suggesting
      that bifenazate acts as a Q(o) inhibitor (Q(o)I). Since these mutations might
      cause cross-resistance to the known acaricidal Q(o)I acequinocyl and
      fluacrypyrim, resistance levels and inheritance patterns were investigated in
      several bifenazate-susceptible and bifenazate-resistant strains with different
      mutations in the cd1 and ef helices aligning the Q(o) pocket. RESULTS: Cross
      resistance to acequinocyl in two bifenazate-resistant strains was shown to be
      maternally inherited and caused by the combination of two specific mutations in
      the cytochrome b Q(o) pocket. Although most investigated strains were resistant
      to fluacrypyrim, resistance was not inherited maternally, but as a monogenic
      autosomal highly dominant trait. As a consequence, there was no correlation
      between cytochrome b genotype and fluacrypyrim resistance. CONCLUSIONS: Although
      there is no absolute cross-resistance between bifenazate, acequinocyl and
      fluacrypyrim, some bifenazate resistance mutations confer cross-resistance to
      acequinocyl. In the light of resistance development and management, high prudence
      is called for when alternating bifenazate and acequinocyl in the same crop.
      Maternally inherited cross-resistance between bifenazate and acequinocyl
      reinforces the likelihood of bifenazate acting as a mitochondrial complex III
      inhibitor at the Q(o) site.

PMID- 19165832
TI  - Purification of flavonoids and triterpene saponins from the licorice extract
      using preparative HPLC under RP and HILIC mode.
AB  - A four-channel preparative HPLC was employed to isolate and purify compounds from
      licorice extract. Two separation modes, RP and hydrophilic interaction LC
      (HILIC), were used in preparative HPLC. HILIC mode was adopted to resolve the
      purification of the compounds with similar hydrophobicity, which were co-eluted
      under RP mode. Using the two separation modes during the purification process,
      fifteen compounds were isolated from licorice extract. The results indicated that
      preparative HPLC performed under HILIC mode is an efficient method for the
      isolation and purification of compounds from natural products.

PMID- 19165833
TI  - Sensitive determination of phenols in environmental water samples with SPE packed
      with bamboo carbon prior to HPLC.
AB  - Bamboo carbon, an inexpensive, readily available material, has attracted great
      attention in recent years because of adsorptive properties. In this paper, the
      potential of bamboo carbon as a SPE adsorbent for the determination of phenols,
      was investigated. Phenols are important environmental contaminants that may
      adversely affect human health. Parameters influencing extraction efficiency,
      including type of eluent, eluent volume, amount of adsorbent, as well as sample
      pH, volume, and flow rate were investigated and optimized. The optimized results
      exhibited excellent linear relationships between peak area and phenol
      concentrations over the range of 2.0-100 ng/mL, with precision between 2.2-7.2%.
      The LODs were 0.06-0.4 ng/mL for the eight phenols tested. The proposed method
      has been successfully applied to the analysis of several real-world environmental
      water samples. These results indicate that bamboo carbon may be used as a novel
      SPE adsorbent for the concentration and determination of phenols in real
      environmental water samples.

PMID- 19165834
TI  - Capillary affinity electrophoresis and ab initio calculation studies of
      valinomycin complexation with Na+ ion.
AB  - In a combined experimental and theoretical approach, the interactions of
      valinomycin (Val), macrocyclic depsipeptide antibiotic ionophore, with sodium
      cation Na(+ )have been investigated. The strength of the Val-Na(+ )complex was
      evaluated experimentally by means of capillary affinity electrophoresis. From the
      dependence of valinomycin effective electrophoretic mobility on the sodium ion
      concentration in the BGE (methanolic solution of 20 mM chloroacetic acid, 10 mM
      Tris, 0-40 mM NaCl), the apparent binding (stability) constant (K(b)) of the Val
      Na(+ )complex in methanol was evaluated as log K(b) = 1.71 +/- 0.16. Besides,
      using quantum mechanical density functional theory (DFT) calculations, the most
      probable structures of the nonhydrated Val-Na(+) as well as hydrated Val
      Na(+).H(2)O complex species were proposed. Compared to Val-Na(+), the optimized
      structure of Val-Na(+).H(2)O complex appears to be more realistic as follows from
      the substantially higher binding energy (118.4 kcal/mol) of the hydrated complex
      than that of the nonhydrated complex (102.8 kcal/mol). In the hydrated complex,
      the central Na(+) cation is bound by strong bonds to one oxygen atom of the
      respective water molecule and to four oxygens of the corresponding C=O groups of
      the parent valinomycin ligand.

PMID- 19165835
TI  - Application of continual injection liquid-phase microextraction method coupled
      with liquid chromatography to the analysis of organophosphorus pesticides.
AB  - A liquid-phase microextraction coupled with LC method has been developed for the
      determination of organophosphorus pesticides (methidation, quinalphos and
      profenofos) in drinking water samples. In this method, a small amount (3 microL)
      of isooctane as the acceptor phase was introduced continually to fill-up the
      channel of a 1.5 cm polypropylene hollow fiber using a microsyringe while the
      hollow fiber was immersed in an aqueous donor solution. A portion of the acceptor
      phase (ca. 0.4 microL) was first introduced into the hollow fiber and additional
      amounts (ca. 0.2 microL) of the acceptor phase were introduced to replenish at
      intervals of 3 min until set end of extraction (40 min). After extraction, the
      acceptor phase was withdrawn and transferred into a 2 mL vial for a drying step
      prior to injection into a LC system. Parameters that affect the extraction
      efficiency were studied including the organic solvent, length of fiber, volume of
      acceptor and donor phase, stirring rate, extraction time, and effect of salting
      out. The proposed method provided good enrichment factors of up to 189.50, with
      RSD ranging from 0.10 to 0.29%, analyte recoveries of over 79.80% and good
      linearity ranging from 10.0 to 1.25 mg/L. The LOD ranged from 2.86 to 82.66
      microg/L. This method was applied successfully to the determination of
      organophosphorus pesticides in selected drinking water samples.

PMID- 19165836
TI  - Determination of spiramycin and neospiramycin antibiotic residues in raw milk
      using LC/ESI-MS/MS and solid-phase extraction.
AB  - A simple confirmatory method for the determination of spiramycin and its
      metabolite neospiramycin in raw milk using LC ESI MS/MS is presented. Macrolide
      residues in raw milk were extracted by ACN, and sample extracts were further
      cleaned up and concentrated using SPE cartridges. Both spiramycin and
      neospiramycin were protonated in electrospray positive ion mode to form singly
      and/or doubly charged pseudomolecular ions. Data acquisition was achieved using
      multiple reaction monitoring, i.e., two transitions, for quantification and
      confirmation. Matrix-matched standard calibration curves were utilized to achieve
      the best accuracy for the method. The method performance was evaluated according
      to both a conventional validation procedure and a designed experimental result.
      The measurement uncertainty arising from accuracy and precision was estimated.
      The method accuracy, expressed as a percentage of an overall recovery, was from
      82.1 to 108.8%, and its intermediate precision was less than 20%. LC/ESI-MS/MS
      method LODs (S/N greater, not dbl equals 3:1) of spiramycin and neospiramycin
      were less than 1.0 microg/kg.

PMID- 19165837
TI  - Strategies for the discovery of new natural products by genome mining.
AB  - Natural products have a very broad spectrum of applications. Many natural
      products are used clinically as antibacterial, antifungal, antiparasitic,
      anticancer and immunosuppressive agents and are therefore of utmost importance
      for our society. When in the 1940s the golden age of antibiotics was ushered in,
      a "gold rush fever" of natural product discovery in the pharmaceutical industry
      ensued for many decades. However, the traditional process of discovering new
      bioactive natural products is generally long and laborious, and known natural
      products are frequently rediscovered. A mass-withdrawal of pharmaceutical
      companies from new natural product discovery and natural products research has
      thus occurred in recent years. In this article, the concept of genome mining for
      novel natural product discovery, which promises to provide a myriad of new
      bioactive natural compounds, is summarized and discussed. Genome mining for new
      natural product discovery exploits the huge and constantly increasing quantity of
      DNA sequence data from a wide variety of organisms that is accumulating in
      publicly accessible databases. Genes encoding enzymes likely to be involved in
      natural product biosynthesis can be readily located in sequenced genomes by use
      of computational sequence comparison tools. This information can be exploited in
      a variety of ways in the search for new bioactive natural products.

PMID- 19165838
TI  - Manipulating cell migration and proliferation with a light-activated polypeptide.
AB  - Remote control of cells: A polypeptide has been made that stimulates
      proliferation and migration of cells upon photochemical activation. This light
      activated polypeptide enables spatially defined control of cell populations at
      the scale of tissue organization; this is accomplished without physically
      contacting the cells or modifying their substrate. Polypeptide growth and
      differentiation factors modulate a wide variety of cell behaviors and can be used
      to manipulate cells in vitro for tissue engineering and basic studies of cell
      biology. To emulate in vitro the spatial aspect of growth factor function, new
      methods are needed to generate defined spatial gradients of activity. Polypeptide
      factors that are engineered to be activated with light provide a method for
      creating concentration gradients with the fine precision in space and time with
      which light can be directed. As a first test of this approach, we have chemically
      synthesized a polypeptide with the sequence of epidermal growth factor in which a
      critical glutamate is "caged" with a photoremovable group. Photolysis of this
      polypeptide afforded maximal mitogenic and chemokinetic activity at
      concentrations at which the caged factor was inactive. Spatially resolved
      photolysis of the factor resulted in spatial patterning of fibroblasts. This
      system will be useful for ex vivo tissue engineering and for investigating the
      interactions of cells with their matrix and the role of chemical gradients in
      biological pattern formation.

PMID- 19165839
TI  - Inhibiting islet amyloid polypeptide fibril formation by the red wine compound
      resveratrol.
AB  - GRAPES FOR AMYLOIDS: The red wine compound resveratrol can effectively inhibit
      the formation of IAPP amyloid that is found in type II diabetes. Our in vitro
      inhibition results do not depend on the antioxidant activity of resveratrol.
      Further, the markedly enhanced cell survival in the presence of resveratrol also
      indicates that the small oligomeric structures that are observed during beta
      sheet formation are not toxic and could be off-pathway assembly products.

PMID- 19165840
TI  - How an inert-gas matrix can modify the molecular properties of lanthanide
      trifluoride.
AB  - Ab initio computations performed on LaF(3) x Ar(n) (n = 1-21) complexes allow a
      quantification of the short-range many-body interactions arising in the argon
      matrix. It is shown that the molecular properties of LaF(3) are strongly
      influenced by the embedding medium. The largest investigated cluster, LaF(3) x
      Ar(21), resembles an hcp structure with the LaF(3) molecule occupying the central
      substitutional site (see figure).

PMID- 19165841
TI  - Ti0.99Pd0.01O(2-delta): a new Pt-free catalyst for high rates of H2 + O2
      recombination with high CO tolerant capacity.
AB  - A platinum-free H(2)/O(2) recombination catalyst, Ti(0.99)Pd(0.01)O(2-delta), is
      synthesized by a solution combustion method where Pd(2+) ions adsorb protonic
      H(2)(delta+) ion and oxygen on the oxide ion vacancy sites (see picture). The
      rate of H(2) + O(2) recombination at 50 degrees C is 15 micromoles g(-1) s(-1),
      which is much higher than that of Pt-containing catalysts.

PMID- 19165842
TI  - Photolysis of the sulfonamide bond of metal complexes of N-dansyl-1,4,7,10
      tetraazacyclododecane in aqueous solution: a mechanistic study and application to
      the photorepair of cis,syn-cyclobutane thymine photodimer.
AB  - Sulfonamide constitutes a ubiquitous functional group that is frequently used in
      organic chemistry, analytical chemistry, and medicinal chemistry. We report
      herein on the photolysis of a dansylamide moiety of 1-dansyl-1,4,7,10
      tetraazzacyclododecane (N-dansylcyclen, L(2)) in the presence of a zinc(II) ion
      in aqueous solution. By potentiometric pH titrations, the complexation constant
      for the 1:1 complex of L(2) and Zn(2+), log K(s)(ZnL(2)), in aqueous solution at
      25 degrees C with I = 0.1 (NaNO(3)) was determined to be 6.5+/-0.1. The structure
      of the ZnL(2) complex was confirmed by single-crystal X-ray diffraction analysis.
      During fluorescence titrations of L(2) with Zn(2+) (irradiation at 308 or 350 nm)
      in aqueous solution at pH 7.4 (10 mM HEPES with I = 0.1 (NaNO(3))) and 25 degrees
      C, considerable enhancement in fluorescence emission of the Zn(2+) complex of
      L(2) (ZnL(2)) was observed, while metal-free L(2) exhibited only a negligible
      emission change upon UV irradiation. It was revealed that this emission
      enhancement arose from the photoinduced cleavage of a sulfonylamide moiety in
      ZnL(2), yielding the Zn(2+)-cyclen complex and 5-dimethylaminonaphthalene-1
      sulfinic acid, which has a greater quantum yield (Phi) for fluorescence emission
      than that of L(2) and ZnL(2). For comparison, the photolysis of N-(1
      naphthalenesulfonyl)cyclen (L(3)) and its Zn(2+) complex (ZnL(3)) under the same
      conditions (irradiation at 313 nm) gave the corresponding sulfonate (1
      naphthylsulfonate). We also describe the results of a photoreversion reaction of
      cis,syn-cyclobutane thymine photodimer (T[c,s]T) utilizing the photolysis of
      ZnL(2) and ZnL(3).

PMID- 19165843
TI  - Ferrocenyl-ended thieno-vinylene oligomers: donor-acceptor polarization and mixed
      valence properties with emphasis on the raman mapping of localized-to-delocalized
      transitions.
AB  - What's your role? New oligothiophene-vinylene compounds have been synthesized to
      study the role of the conjugated chain in two different cases (see scheme;
      MV=mixed valence). The electronic and molecular structures were analyzed by means
      of electronic, X-ray photoelectron, and Raman spectroscopy, together with thermo
      spectroscopy, electrochemistry, and DFT calculations.New oligothiophene-vinylene
      compounds have been synthesized in order to study the role of the conjugated
      chain in two different cases: 1) when push-pull action operates between an
      electron-donor and an electron-acceptor group at the ends of the thiophene
      vinylene conjugated chain, and 2) when mixed-valence action is induced by single
      oxidation of the same chain functionalized at both terminal positions with
      ferrocene groups leading to competition between the donor groups. The electronic
      and molecular structures are analyzed by means of electronic, X-ray photoelectron
      and Raman spectroscopies, together with thermospectroscopy, electrochemistry and
      density functional theory calculations. The cyclic voltammetry processes have
      been followed by spectrochemistry. It is shown that the radical cation of the
      diferrocenyl derivative is a class III mixed-valence system (i.e., fully
      delocalized) according to its Raman spectrum. Moreover, by Raman thermo
      spectroscopy the thermal transition of this radical cation from a delocalized
      (class III, room temperature) to a localized (class II, -160 degrees C) state is
      scanned. In all cases the Raman study is paralleled by an electronic absorption
      spectroscopic analysis. Structure-property relationships are proposed for
      molecules of two important fields of very active research as that of the non
      linear optics (i.e., organic optoelectronic) and that of the mixed-valence
      systems (i.e., charge-transfer processes).

PMID- 19165844
TI  - Structure elucidation and NMR assignments for three anthraquinone derivatives
      from the marine fungus Fusarium sp. (No. ZH-210).
AB  - The structure elucidations and complete (1)H and (13)C NMR assignments are
      reported for three new anthraquinone derivatives: Fusaquinon A (1), B (2), and C
      (3) isolated from the fermentation medium of the marine fungus Fusarium sp. (No.
      ZH-210). HREIMS, Fourier transform infrared absorption spectrometry (FT-IR), NMR
      experiments including gCOSY, gHMQC, gHMBC, and NOESY were used for the
      determination of the structures and NMR spectral assignments. Preliminary
      pharmacological test showed that they exhibited low cytotoxic activity towards
      KB, KBv200, and MCF-7 cell lines.

PMID- 19165845
TI  - (1)H and (13)C NMR assignments of eight nitrogen containing compounds from
      Nocardia alba sp.nov (YIM 30243(T)).
AB  - An unprecedented new natural product named nocarsin A (1), 5H-4a,6,7a
      triazacyclopenta[cd]indene-5,7(6H)-dione (1), together with seven known compounds
      lumichrome (2), cyclo (L-Leu-L-Tyr) (3), cyclo (L-Ala-L-Ile) (4), cyclo (L-Ala-L
      Leu) (5), cyclo (L-Val-L-Ala) (6), 5-methyluracil (7) and uracil (8), was
      isolated from Nocardia alba sp.nov (YIM 30243(T)), which was isolated from a soil
      sample collected from Yunnan Province, P. R. China. NMR techniques including
      COSY, HSQC, ROESY, and HMBC were used to elucidate the structures of these
      compounds. We report the unambiguous assignments of the (1)H and (13)C NMR
      spectra of the new compound nocarsin A (1).

PMID- 19165846
TI  - Stabilization of an alpha helix by beta-sheet-mediated self-assembly of a
      macrocyclic peptide.
AB  - Protein roll call: Peptide-based building blocks, in which both an alpha-helix
      forming segment and a beta-sheet segment are located within a single macrocyclic
      structure, self-assemble into alpha-helix-decorated artificial proteins. This
      approach provides a starting point for developing artificial proteins that can
      modulate alpha-helix-mediated interactions occurring in a multivalent fashion.

PMID- 19165847
TI  - Heteroanalogues of PCBM: N-bridged imino-PCBMs for organic field-effect
      transistors.
AB  - Crossing the bridge: Two isomeric iminofullerenes, [5,6]-open azafulleroid 1 and
      [6,6]-closed aziridinofullerene 2, were prepared by cycloaddition of an organic
      azide to C(60). These "azalogues" enable the study of the effects of the bridging
      atom in a fullerene cage, that is, C(60)-like (5,6-open) versus PCBM-like (6,6
      closed), as a function of their pi systems (PCBM = [6,6]-phenyl-C(61)-butyric
      acid methyl ester).

PMID- 19165848
TI  - Catalytic asymmetric synthesis of 2,2-disubstituted oxetanes from ketones by
      using a one-pot sequential addition of sulfur ylide.
AB  - Better the second time around: The title compounds were synthesized by using a
      one-pot double methylene transfer catalyzed by a heterobimetallic La/Li complex.
      Chiral amplification in the second step was the key to obtaining oxetanes in high
      enantiomeric excess (see scheme).

PMID- 19165849
TI  - Lighting up H2O2: the molecule that is a "necessary evil" in the cell.
AB  - A cunning plan: In the multifunctional fluorescent probe MitoPY1 the phosphonium
      head group (red) targets mitochondria and the boronate group (green) responds to
      hydrogen peroxide. MitoPY1 reacts selectively with mitochondrial H(2)O(2) in
      living cells, and an increase in fluorescence is triggered by the conversion of
      MitoPY1 into MitoPY1ox (yellow).

PMID- 19165850
TI  - Fluorescence signal amplification by cation exchange in ionic nanocrystals.
AB  - Lighting-up time: A cation-exchange reaction releases thousands of divalent
      cations from nonfluorescent CdSe ionic crystals and triggers fluorescence from
      thousands of originally nonfluorescent Fluo-4 fluorophores to obtain a large
      fluorescence amplification (see picture) and a low detection limit in bioassays.
      The technique is fast, simple, with a large dye-to-reporter labeling ratio, and
      flexible in selection of nanocrystals and fluorophores.

PMID- 19165851
TI  - Local probe oxidation of self-assembled monolayers: templates for the assembly of
      functional nanostructures.
AB  - The local oxidation of self-assembled monolayers with a scanning probe is a
      promising method for the generation of structures with chemical functionalities
      on the nanometer scale. This technique, which takes advantage of the chemical
      stability and versatility of self-assembled monolayers and the ability to pattern
      these monolayers by scanning-probe-based oxidation methods, enables the
      hierarchical assembly of complex structures in a controlled manner. Surface
      modification can be followed by the assembly of a further functional monolayer
      and/or additional surface-modification reactions in the targeted, sequential
      construction of functional device features.

PMID- 19165852
TI  - Molecular catalysts that oxidize water to dioxygen.
AB  - During the past four years we have witnessed a revolution in the field of water
      oxidation catalysis, in which well-defined molecules are opening up entirely new
      possibilities for the design of more rugged and efficient catalysts. This
      revolution has been stimulated by two factors: the urgent need for clean and
      renewable fuel and the intrinsic human desire to mimic nature's reactions, in
      this case the oxygen-evolving complex (OEC) of the photosystem II (PSII). Herein
      we give a short general overview of the established basis for the oxidation of
      water to dioxygen as well as presenting the new developments in the field.
      Furthermore, we describe the new avenues these developments are opening up with
      regard to catalyst design and performance, together with the new questions they
      pose, especially from a mechanistic perspective. Finally the challenges the field
      is facing are also discussed.

PMID- 19165853
TI  - Apoenzyme reconstitution as a chemical tool for structural enzymology and
      biotechnology.
AB  - Many enzymes contain a nondiffusible organic cofactor, often termed a prosthetic
      group, which is located in the active site and essential for the catalytic
      activity of the enzyme. These cofactors can often be extracted from the protein
      to yield the respective apoenzyme, which can subsequently be reconstituted with
      an artificial analogue of the native cofactor. Nowadays a large variety of
      synthetic cofactors can be used for the reconstitution of apoenzymes and, thus,
      generate novel semisynthetic enzymes. This approach has been refined over the
      past decades to become a versatile tool of structural enzymology to elucidate
      structure-function relationships of enzymes. Moreover, the reconstitution of
      apoenzymes can also be used to generate enzymes possessing enhanced or even
      entirely new functionality. This Review gives an overview on historical
      developments and the current state-of-the-art on apoenzyme reconstitution.

PMID- 19165854
TI  - Identification of CCDC62-2 as a novel cancer/testis antigen and its
      immunogenicity.
AB  - Cancer/testis (CT) antigens are expressed in normal germ line tissues and various
      cancers. They are considered promising target molecules for immunotherapy for
      patients with various cancers. To identify CT antigens, we performed serological
      identification of antigens by recombinant expression cloning. The humoral immune
      response of cancer patients against a newly defined antigen was analyzed. A
      testicular cDNA library was immunoscreened with serum obtained from a gastric
      adenocarcinoma patient whose primary cancer had regressed once and most liver
      metastases had disappeared transiently. We isolated 55 positive cDNA clones
      comprising 23 different genes. They included 4 genes with testis-specific
      expression profiles in the Unigene database, including coiled-coil domain
      containing 62 (CCDC62). RT-PCR analysis showed that the expression of 2 splice
      variants of CCDC62 was restricted to the testis in normal adult tissues. In
      malignant tissues, CCDC62 variant 2 (CCDC62-2) was aberrantly expressed in a
      variety of cancers, including stomach cancer. A serological survey of 191 cancer
      patients with a range of different cancers by ELISA revealed antibodies to CCDC62
      2 in 13 patients, including stomach cancer. None of the 41 healthy donor serum
      samples were reactive in the same test. The serum reaction against CCDC62-2 was
      confirmed by western blot. CCDC62-2 is a CT antigen that is immunogenic in cancer
      patients.

PMID- 19165855
TI  - Epstein-Barr virus and the pathogenesis of Burkitt's lymphoma: more questions
      than answers.
AB  - Burkitt's lymphoma (BL) was first described as a clinical entity in children in
      Central Africa by Denis Burkitt in 1958. The particular epidemiological features
      of this tumor initiated the search for a virus as the causative agent and led to
      the discovery of Epstein-Barr virus (EBV) by Epstein and coworkers in 1964. It
      became apparent in the seventies and eighties that the tumor is not restricted to
      Central Africa, but occurs with lesser incidence all over the world (sporadic BL)
      and is also particularly frequent in HIV infected individuals, and that not all
      BL cases are associated with EBV: about 95% of the cases in Central Africa, 40 to
      50% of the cases in HIV-infected individuals and 10 to 20% of the sporadic cases
      harbour the viral information and express at least one viral antigen (EBNA1) and
      a number of non-coding viral RNAs. In contrast, all BL cases regardless of their
      geographical origin exhibit one of three c-myc/Ig chromosomal translocations
      leading to the activation of the c-myc gene as a crucial event in the development
      of this disease. Although epidemiological evidence clearly points to a role of
      the virus in the African cases, the role of EBV in the pathogenesis of BL has
      remained largely elusive. This review summarizes current concepts and ideas how
      EBV might contribute to the development of BL in the light of the progress made
      in the last decade and discusses the problems of the experimental systems
      available to test such hypotheses.

PMID- 19165856
TI  - Adjuvant targeted therapy in early breast cancer.
AB  - For this review, the authors appraised the evidence for adjuvant trastuzumab
      therapy in early breast cancer. There was level 1 evidence to support the routine
      use of 1 year of adjuvant trastuzumab in conjunction with chemotherapy for women
      with human epidermal growth factor receptor 2 (HER-2)-positive early breast
      cancer. The relative benefits of concurrent versus sequential administration
      remained unclear; however concurrent administration permitted the earliest
      possible intervention with trastuzumab with possible superiority. There was
      evidence to support the use of trastuzumab in both lymph node-positive and high
      risk lymph node-negative patients, and preliminary data suggested that all
      patient subgroups that were eligible for the trials benefit equally from
      trastuzumab. Adjuvant trastuzumab was associated with a risk of cardiotoxicity,
      the long-term impact of which remains largely unknown. Routine cardiac risk
      assessment considering left ventricular ejection fraction, age, and prior history
      of cardiac events is recommended along with the selection of trastuzumab-based
      regimens that minimize cardiotoxicity. Trastuzumab acquisition costs for 1 year
      of therapy were the largest component of treatment costs.

PMID- 19165857
TI  - Long-term risk of cardiovascular disease in Hodgkin lymphoma survivors-
      retrospective cohort analyses and a concept for prospective intervention.
AB  - Previous studies have shown increased cardiovascular mortality as late side
      effects in Hodgkin lymphoma (HL) patients. This study identifies stratifying risk
      factors for surveillance and defines concepts for a clinical feasible and
      noninvasive prospective protocol for intervention of cardiovascular side effects.
      HL patients diagnosed between 1965 and 1995 (n = 6.946) and their first-degree
      relatives (FDR) were identified through the Swedish Cancer Registry and the
      Swedish Multigeneration Registry. For the HL and FDR cohort, in-patient care for
      cardiovascular disease (CVD) was registered through the Hospital Discharge
      Registry, Sweden. Standard incidence ratios of developing CVD for the HL cohort
      were calculated. A markedly increased risk for in-patient care of CVD was
      observed in HL patients with HL diagnosed at age 40 years or younger and with
      more than 10 years follow-up. In the HL survivors, a family history of congestive
      heart failure (CHF) and coronary artery disease (CAD) increased the risk for
      these diseases. The Swedish Hodgkin Intervention and Prevention study started in
      2007. In the pilot feasibility study for prospective intervention (47 patients),
      about 25% of the cases had side effects and laboratory abnormalities. These
      patients were referred to a cardiologist or general practitioner. In the
      prospective cohort, a positive family history for CHF or CAD could be a
      stratifying risk factor when setting up a surveillance model. The prospective on
      going study presents an intervention model that screens and treats for
      comorbidity factors. This article also presents an overview of the study concept.

PMID- 19165858
TI  - Molecular mechanisms involved in activity of h7C10, a humanized monoclonal
      antibody, to IGF-1 receptor.
AB  - IGF-1 receptor (IGF-1R) plays a key role in the development of numerous tumors.
      Blockade of IGF-1R axis using monoclonal antibodies constitutes an interesting
      approach to inhibit tumor growth. We have previously shown that h7C10, a
      humanized anti-IGF-1R Mab, exhibited potent antitumor activity in vivo. However,
      mechanisms of action of h7C10 are still unknown. Here, we showed that h7C10
      inhibited IGF-1-induced IGF-1R phosphorylation in a dose-dependent manner. Also,
      h7C10 abolished IGF-1-induced activation of PI3K/AKT and MAPK pathways. Cell
      cycle progression and colony formation were affected in the presence of h7C10
      probably because of the inhibition of IGF-1-induced cyclin D1 and E expression.
      In addition, we demonstrated that h7C10 induced a rapid IGF-1R internalization
      leading to an accumulation into cytoplasm resulting in receptor degradation.
      Using lysosome and proteasome inhibitors, we observed that the IGF-1R alpha- and
      beta-chains could follow different degradation routes. Thus, we demonstrated that
      antitumoral properties of h7C10 are the result of IGF-1-induced cell signaling
      inhibition and down-regulation of IGF-1R level suggesting that h7C10 could be a
      candidate for therapeutic applications.

PMID- 19165859
TI  - Shikonin exerts antitumor activity via proteasome inhibition and cell death
      induction in vitro and in vivo.
AB  - Dysregulation of the ubiquitin-proteasome pathway plays an essential role in
      tumor growth and development. Shikonin, a natural naphthoquinone isolated from
      the traditional Chinese medicine Zi Cao (gromwell), has been reported to possess
      tumor cell-killing activity, and results from a clinical study using a shikonin
      containing mixture demonstrated its safety and efficacy for the treatment of late
      stage lung cancer. In this study, we reported that shikonin is an inhibitor of
      tumor proteasome activity in vitro and in vivo. Our computational modeling
      predicts that the carbonyl carbons C(1) and C(4) of shikonin potentially interact
      with the catalytic site of beta 5 chymotryptic subunit of the proteasome. Indeed,
      shikonin potently inhibits the chymotrypsin-like activity of purified 20S
      proteasome (IC(50) 12.5 micromol/L) and tumor cellular 26S proteasome (IC(50)
      between 2-16 micromol/L). Inhibition of the proteasome by shikonin in murine
      hepatoma H22, leukemia P388 and human prostate cancer PC-3 cultures resulted in
      accumulation of ubiquitinated proteins and several proteasome target proapoptotic
      proteins (I kappaB-alpha, Bax and p27), followed by induction of cell death.
      Shikonin treatment resulted in tumor growth inhibition in both H22 allografts and
      PC-3 xenografts, associated with suppression of the proteasomal activity and
      induction of cell death in vivo. Finally, shikonin treatment significantly
      prolonged the survival period of mice bearing P388 leukemia. Our results indicate
      that the tumor proteasome is one of the cellular targets of shikonin and
      inhibition of the proteasome activity by shikonin contributes to its antitumor
      property.

PMID- 19165860
TI  - Factors associated with incident and fatal pancreatic cancer in a cohort of
      middle-aged women.
AB  - Risk factors for pancreatic cancer, other than smoking and diabetes, are not well
      established, especially for women. In a cohort of 1.3 million middle-aged women,
      followed for 9.2 million person-years for cancer incidence and 11.5 million
      person-years for mortality, there were 1,338 incident pancreatic cancer cases and
      1,710 deaths from the disease. Using proportional hazards models, we calculated
      adjusted relative risks (RRs) and 95% confidence intervals (CIs) by smoking,
      height, body mass index (BMI), alcohol consumption, physical activity and history
      of diabetes. Pancreatic cancer incidence was greater in current than never
      smokers (RR 2.39, CI 2.10-2.73), the risk increasing with the number of
      cigarettes smoked. The incidence of pancreatic cancer also increased with
      increasing BMI (RR 1.34, CI 1.13-1.57 for BMI >or= 30 vs. 22.5-25 kg/m(2)), and
      with a history of diabetes (RR 1.58, CI 1.22-2.03, with vs. without such a
      history). These factors were also associated with increased mortality from
      pancreatic cancer. Height, alcohol consumption and physical activity showed
      little or no association with pancreatic cancer risk.

PMID- 19165861
TI  - The Bcl-xL inhibitor of apoptosis is preferentially expressed in cutaneous
      squamous cell carcinoma compared with that in keratoacanthoma.
AB  - Keratoacanthoma (KA) is difficult to histologically distinguish from squamous
      cell carcinoma (SCC). Therefore, although KA is a benign self-resolving skin
      lesion, KA is commonly treated as SCC. Biomarkers to distinguish KA and SCC would
      thus be desirable. In search for specific markers, paraffin-embedded tissue
      samples from 25 SCC and 64 KA were arranged in a tissue microarray (TMA) and
      stained for immunologic cell-markers CD3, CD20 and CD68 as well as for proteins
      considered of relevance in tumorgenesis, namely NF kappaB/p65, I kappaB-alpha,
      STAT3, p53, TRAP-1, pRB, phosphorylated pRb, Cyld, p21, p16(INK4), Survivin, Bcl
      xL, Caspase 3, Bak, FLK-1/VEGF-r2 and Ki-67. In addition, the tumors were tested
      for presence of human papillomavirus by PCR. We detected that the two lesions
      differed significantly in expression of Bcl-xL which was present in 84% of the
      SCC compared with only 15% in the KA (p < 0.001). The lower expression of the
      antiapoptotic protein Bcl-xL in KA is consistent with a possible role of
      apoptosis in the regression of KA.

PMID- 19165862
TI  - Meat intake and meat preparation in relation to risk of postmenopausal breast
      cancer in the NIH-AARP diet and health study.
AB  - A number of studies have reported that intake of red meat or meat cooked at high
      temperatures is associated with increased risk of breast cancer, but other
      studies have shown no association. We assessed the association between meat, meat
      cooking methods, and meat-mutagen intake and postmenopausal breast cancer in the
      NIH-AARP Diet and Health Study cohort of 120,755 postmenopausal women who
      completed a food frequency questionnaire at baseline (1995-1996) as well as a
      detailed meat-cooking module within 6 months following baseline. During 8 years
      of follow-up, 3,818 cases of invasive breast cancer were identified in this
      cohort. Cox proportional hazards models were used to estimate hazard ratios (HR)
      and 95% confidence intervals (95% CI). After adjusting for covariates, intake of
      total meat, red meat, meat cooked at high temperatures, and meat mutagens showed
      no association with breast cancer risk. This large prospective study with
      detailed information on meat preparation methods provides no support for a role
      of meat mutagens in the development of postmenopausal breast cancer.

PMID- 19165863
TI  - PDGF-B induces a homogeneous class of oligodendrogliomas from embryonic neural
      progenitors.
AB  - We describe the generation of mouse gliomas following the overexpression of PDGF
      B in embryonic neural progenitors. Our histopathological, immunohistochemical and
      genome-wide expression analyses revealed a surprising uniformity among PDGF-B
      induced tumors, despite they were generated by transducing a highly heterogeneous
      population of progenitor cells known for their ability to produce all the cell
      types of the central nervous system. Comparison of our microarray data with
      published gene expression data sets for many different murine neural cell types
      revealed a closest correlation between our tumor cells and oligodendrocyte
      progenitor cells, confirming definitively that PDGF-B-induced gliomas are pure
      oligodendrogliomas. Importantly, we show that this uniformity is likely due to
      the ability of PDGF-B overexpression to respecify competent embryonic neural
      precursors toward the oligodendroglial lineage, providing evidence that the
      transforming activity of PDGF-B is influenced by the developmental potential of
      the targeted cells. Interestingly, we found that PDGF-B-induced tumors harbor
      different proliferating cell populations. However only PDGF-B-overexpressing
      cells are tumorigenic, indicating that paracrine signaling from the tumor is
      unable to transform bystander cells.

PMID- 19165864
TI  - Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats.
AB  - Tetrandrine, a bisbenzylisoquinoline alkaloid, has antitumor effects against some
      cancers, but its effects on gliomas are unknown. In this study, we investigated
      the effects of tetrandrine on the growth and angiogenesis of rat RT-2 gliomas. We
      treated RT-2 glioma cells with tetrandrine and then measured cytotoxicity,
      apoptosis and expression of vascular endothelial growth factor (VEGF). We also
      examined the cytotoxic effect of tetrandrine on the ECV304 human umbilical vein
      endothelial cells and the effects of tetrandrine on the in vivo angiogenesis.
      Tumor size and animal survival were followed in tetrandrine-treated rats with
      subcutaneous or intracerebral gliomas. Expression of CD31 in tetrandrine-treated
      gliomas was followed to study its effect on glioma-induced angiogenesis.
      Tetrandrine had cytotoxic effects and induced apoptosis of glioma cells in a
      concentration- and time-dependent manner. Tetrandrine also inhibited the
      expression of VEGF in glioma cells, induced cytotoxicity effect on the ECV304
      cells and suppressed the in vivo angiogenesis. Tetrandrine (150 mg/kg/day) had
      significant antitumor effects on subcutaneous tumors and led to slower tumor
      growth rate, longer animal survival time and higher animal survival (p < 0.05).
      Tetrandrine also affected intracerebral tumors and prolonged animal survival (p <
      0.05) without affecting survival rate. Immunohistochemical analyses showed that
      the subcutaneous gliomas from tetrandrine-treated rats had fewer microvessel
      densities than control rats (p = 0.01). The results demonstrate that tetrandrine
      is cytotoxic to RT-2 glioma cells, has antitumor effects on subcutaneous and
      intracerebral gliomas, and inhibits angiogenesis in subcutaneous gliomas.
      Tetrandrine has potential as a treatment for gliomas.

PMID- 19165866
TI  - Doxorubicin and mitoxantrone drug eluting beads for the treatment of experimental
      peritoneal carcinomatosis in colorectal cancer.
AB  - We investigated the therapeutic efficiency of sulfonate-modified polyvinyl
      alcohol beads loaded with doxorubicin, irinotecan or mitoxantrone in vitro and in
      vivo in a model of experimental peritoneal carcinomatosis (PC). In vitro, cell
      proliferation was efficiently impaired by doxorubicin drug eluting bead (DEB)
      treatment while mitoxantrone DEBs were less effective than. Irinotecan showed
      little effect for both DEBs and free drug. Apoptosis was not different between
      free mitoxantrone and the DEB form while more apoptosis induction was observed in
      cells incubated with free doxorubicin and irinotecan. Experimental PC was
      produced in mice. The therapeutic efficiency of either mitoxantrone and
      doxorubicin DEB or free drugs were compared. Mice were treated either once on day
      12 or by 3 repetitive applications on days 7, 10 and 12. Mice treated by DEBs
      showed less weight loss and mortality. Therapeutic effect was determined by
      measuring tumor volume and tumor load on the day 15 after tumor inoculation. For
      the single application on the day 12, an advantage could be observed for the free
      drugs. After 3 repeated injections of both free and mitoxantrone DEB no
      difference in tumor load or tumor volume could be observed. Least tumor load and
      tumor volume was observed in mice that received 3 repeated injections of
      doxorubicin DEB. No animal survived 3 injections of free doxorubicin. We conclude
      that bead encapsulation of chemotherapeutic drugs may show the advantage of less
      toxicity in peritoneal spread of colorectal cancer.

PMID- 19165867
TI  - Season of cancer diagnosis exerts distinct effects upon short- and long-term
      survival.
AB  - Several epidemiological studies have shown an association between the season in
      which certain cancers are diagnosed and survival, with diagnosis in summer and
      autumn being associated with better survival. In this study, we have added
      resolution to the analysis of seasonality in cancer survival by considering
      mortality within several nonoverlapping time periods following diagnosis, thereby
      quantifying the separate contributions of mechanisms operating in the short term
      and in the longer term. We found evidence of seasonality acting on mortality
      within 2 distinct periods following diagnosis. Diagnosis in the summer was
      associated with substantially decreased mortality within the first month of
      diagnosis compared with winter in men with prostate cancer, those of both sexes
      with colorectal or lung cancer, and most strikingly, amongst women with breast
      cancer (hazard ratio 0.81 [95% confidence interval 0.75-0.86]). Adjusting for
      monthly variations in general mortality greatly attenuated the seasonal effects
      on short-term mortality. At long-term follow-up (>5 years), there was a
      consistent shift in the seasonality pattern, with autumn diagnosis alone being
      associated with decreased mortality, both in female breast cancer cases and in
      lung cancer cases of both sexes. We conclude that the higher survival observed
      amongst patients diagnosed in summer and autumn is predominantly a short-term
      phenomenon that is largely attributable to generally higher mortality in winter.
      However, the distinct mortality reduction observed in the long term amongst those
      diagnosed in the autumn, especially amongst breast cancer patients, may indicate
      the presence of a seasonally variable protective mechanism.

PMID- 19165865
TI  - Inhibition of matrix metalloproteinase-2 enhances radiosensitivity by abrogating
      radiation-induced FoxM1-mediated G2/M arrest in A549 lung cancer cells.
AB  - Matrix metalloproteinase-2 (MMP-2), is known to degrade the collagen IV, plays a
      role in radiation-induced lung injury. We therefore investigated the antitumor
      effects of combining MMP-2 inhibition using an adenovirus expressing siRNA
      against MMP-2 (Ad-MMP-2-Si) with radiation therapy (IR) on A549 lung cancer cells
      in vitro and in vivo. IR increased MMP-2 mRNA, protein and activity in lung
      cancer cells. MMP-2 inhibition along with IR enhanced radiosensitivity as
      determined by clonogenic assay, flow cytometry and TUNEL assay. We show that MMP
      2 inhibition prior to irradiation reduced p53 phosphorylation, with a
      corresponding reduction in the expression of the p53 downstream target gene
      p21(Cip1/Waf1). Irradiated tumor cells induced the FoxM1-mediated DNA repair
      gene, XRCC1 and Checkpoint kinases 2/1, which were abrogated with combined
      treatment of Ad-MMP-2-Si and IR. Further, the combination of Ad-MMP-2-Si with
      radiotherapy significantly increased antitumor efficacy in vivo compared to
      either agent alone. Indeed, histological analysis of tumor sections collected
      from the combination group revealed more apoptotic cells. These studies suggest
      that MMP-2 inhibition in combination with radiotherapy abrogates G2 cell cycle
      arrest leading to apoptosis and provide evidence of the antitumor efficacy of
      combining MMP-2 inhibition with irradiation as a new therapeutic strategy for the
      effective treatment of NSCLC patients.

PMID- 19165868
TI  - Roles of ezrin in the growth and invasiveness of esophageal squamous carcinoma
      cells.
AB  - Ezrin, which crosslinks the cytoskeleton and plasma membrane, is involved in the
      growth and metastatic potential of cancer cells. Ezrin expression in esophageal
      squamous cell carcinoma (ESCC) was described recently, but its roles and the
      underlying mechanism(s) remain unclear. In our study, we first showed that ezrin
      in ESCC cell is expressed in the nucleus as well as in the cytoplasm and plasma
      membrane. Then, by using RNAi, we revealed that interference of ezrin expression
      suppressed the growth, adhesion and invasiveness of ESCC cells. Tumorigenesis
      experiments revealed that ezrin may directly regulate tumor formation in vivo. To
      explore the molecular mechanisms through which ezrin contributes to the
      proliferation and invasiveness of ESCC cells, we used cDNA microarrays to analyze
      ezrin knockdown cells and the control cells; of 39,000 genes examined, 297 were
      differentially expressed upon ezrin knockdown, including some proliferation- and
      invasiveness-related genes such as ATF3, CTGF and CYR61. Furthermore, pathway
      analysis showed that ezrin knockdown led to decreased activation of the TGF-beta
      and MAPK pathways, and ezrin-mediated cell invasiveness alteration was dependent
      on the activation of these pathways. Finally, immunohistochemical staining on 80
      ESCC specimens and 50 normal esophageal mucosae revealed that the expression
      levels of 3 altered genes involved in the regulation of cell proliferation and
      tumor metastasis, including CTGF, CYR61 and ATF3, were altered in ESCCs, and
      their expression pattern correlated with ezrin expression. Taken together, we
      propose that ezrin might function in the growth and invasiveness of ESCC cells
      through the MAPK and TGF-beta pathways.

PMID- 19165869
TI  - DNA methylation of microRNA genes in gastric mucosae of gastric cancer patients:
      its possible involvement in the formation of epigenetic field defect.
AB  - Accumulation of aberrant DNA methylation in normal-appearing gastric mucosae,
      mostly induced by H. pylori infection, is now known to be deeply involved in
      predisposition to gastric cancers (epigenetic field defect), and silencing of
      protein-coding genes has been analyzed so far. In this study, we aimed to clarify
      the involvement of microRNA (miRNA) gene silencing in the field defect. First, we
      selected three miRNA genes as methylation-silenced after analysis of six
      candidate "methylation-silenced" tumor-suppressor miRNA genes. Methylation levels
      of the three genes (miR-124a-1, miR-124a-2 and miR-124a-3) were quantified in 56
      normal gastric mucosae of healthy volunteers (28 volunteers with H. pylori and 28
      without), 45 noncancerous gastric mucosae of gastric cancer patients (29 patients
      with H. pylori and 16 without), and 28 gastric cancer tissues (13 intestinal and
      15 diffuse types). Among the healthy volunteers, individuals with H. pylori had
      7.8-13.1-fold higher methylation levels than those without (p < 0.001). Among
      individuals without H. pylori, noncancerous gastric mucosae of gastric cancer
      patients had 7.2-15.5-fold higher methylation levels than gastric mucosae of
      healthy volunteers (p < 0.005). Different from protein-coding genes, individuals
      with past H. pylori infection retained similar methylation levels to those with
      current infection. In cancer tissues, methylation levels were highly variable,
      and no difference was observed between intestinal and diffuse histological types.
      This strongly indicated that methylation-silencing of miRNA genes, in addition to
      that of protein-coding genes, contributed to the formation of a field defect for
      gastric cancers.

PMID- 19165871
TI  - Re: Impact on quality of life after mastoid obliteration.

PMID- 19165870
TI  - Older individuals appear to acquire mitotically older colorectal cancers.
AB  - The incidence of many common cancers increases with ageing. The purpose of this
      study is to infer whether cancer mitotic ages (total numbers of divisions since
      the zygote) also increase with chronological age. Mitotic ages may be inferred by
      counting numbers of replication errors or neutral passenger changes. Methylation
      at certain CpG-rich sequences or 'tags' appears to be proportional to mitotic
      age, because age-related increases in tag methylation are observed in mitotic
      tissues such as the colon. Such passenger tag methylation was measured by
      bisulphite sequencing from 16 colorectal cancers from differently aged male
      individuals. Both normal colon and cancers exhibited significant age-related
      increases in tag methylation, but cancer methylation was significantly higher.
      Therefore, older individuals appear to have mitotically older colorectal cancers.
      Cell division per se may be an important mechanism underlying the increased
      incidence of colorectal cancer with ageing, because the neoplastic phase appears
      more commonly to start from mitotically older crypt stem cells.

PMID- 19165874
TI  - Across the great divide: introduction to the special issue on psychology in
      medicine.
AB  - Health psychology has made limited progress becoming an accepted part of
      mainstream medical research and practice. Although abundant efficacy research has
      generated considerable evidence-based interventions that are effective primary
      medical interventions or adjuncts to other medical treatments, evidence of
      acceptance within medicine and especially primary care is meager. This special
      edition of the Journal of Clinical Psychology is an effort to assist movement in
      this area. It is a combination of commentaries concerning aspects of clinical
      collaboration within primary care, a discussion of issues that are barriers to
      implementation, and a wide range of research efforts supporting models of
      collaborative interventions between health psychology and primary care. It also
      identifies mechanisms that may account for the effectiveness of certain types of
      interventions. Taken as a whole the volume supports the importance and viability
      of clinical health psychology research and practice in an area of fundamental
      importance--the general health of patients in medical settings--the location
      where most people present psychological problems and receive treatment in
      response.

PMID- 19165875
TI  - Contribution of the tooth bud mesenchyme to alveolar bone.
AB  - This study highlights the dynamic nature of the mesenchymal cells during tooth
      development from the bud to the bell stage. Condensing mesenchymal cells,
      labelled on either side of the developing tooth bud, move toward the presumptive
      roots forming an arc of cells under the dental papilla. These labelled cells take
      part in formation of the dental follicle, which contributes to both the tooth and
      its surrounding periodontium, including the supporting alveolar bone. This study,
      thus, physically links development of the tooth with the tissue into which it
      develops. The results obtained clearly indicate that the tooth organ is an entity
      comprising dental and periodontal tissue.

PMID- 19165876
TI  - Reduced power magnetic resonance spectroscopic imaging of the prostate at 4.0
      Tesla.
AB  - Proton magnetic resonance spectroscopic imaging (MRSI) of the prostate has been
      described at 1.5 T and 3 T as a means of localizing prostate cancers with high
      sensitivity and specificity. This technique could be improved by increasing the
      field strength further; however, it has not been described in detail above 3 T.
      To address the increase in B1 and SAR at high field strengths, a new protocol is
      described for reduced power STEAM MRSI of the prostate at 4.0 Tesla, using a
      pelvic surface coil array for RF transmission and reception, and a solid,
      reusable endorectal coil for reception only. The optimal STEAM sequence timing
      parameters for observation of the strongly coupled citrate spin system were
      determined through simulation to be echo time (TE) = 27 ms and mixing time (TM) =
      27 ms, and the results were verified in vitro. Power reduction was achieved by
      applying the VERSE method to each of the three slice selective pulses in the
      STEAM sequence, and the B(1)max and SAR were reduced by 43% and 36%,
      respectively. Finally, in vivo spectroscopic imaging data were acquired from a
      prostate cancer patient, demonstrating the detection of citrate, choline, and
      creatine with 0.37 cc nominal resolution in a 10 minute scan.

PMID- 19165877
TI  - Use of magnetic nanoparticles to monitor alginate-encapsulated betaTC-tet cells.
AB  - Noninvasive monitoring of tissue-engineered constructs is an important component
      in optimizing construct design and assessing therapeutic efficacy. In recent
      years, cellular and molecular imaging initiatives have spurred the use of iron
      oxide-based contrast agents in the field of NMR imaging. Although their use in
      medical research has been widespread, their application in tissue engineering has
      been limited. In this study, the utility of monocrystalline iron oxide
      nanoparticles (MIONs) as an NMR contrast agent was evaluated for betaTC-tet cells
      encapsulated within alginate/poly-L-lysine/alginate (APA) microbeads. The
      constructs were labeled with MIONs in two different ways: 1) MION-labeled betaTC
      tet cells were encapsulated in APA beads (i.e., intracellular compartment), and
      2) MION particles were suspended in the alginate solution prior to encapsulation
      so that the alginate matrix was labeled with MIONs instead of the cells (i.e.,
      extracellular compartment). The data show that although the location of cells can
      be identified within APA beads, cell growth or rearrangement within these
      constructs cannot be effectively monitored, regardless of the location of MION
      compartmentalization. The advantages and disadvantages of these techniques and
      their potential use in tissue engineering are discussed.

PMID- 19165878
TI  - Sensitivity to tumor microvasculature without contrast agents in high spectral
      and spatial resolution MR images.
AB  - Contrast-enhanced (CE)-MRI is sensitive to cancers but can produce adverse
      reactions and suffers from insufficient specificity and morphological detail.
      This research investigated whether high spectral and spatial resolution (HiSS)
      MRI detects tumor vasculature without contrast agents, based on the sensitivity
      of the water resonance line shape to tumor blood vessels. HiSS data from AT6.1
      tumors inoculated in the hind legs of rats (N = 8) were collected pre- and post
      blood pool contrast agent (iron-oxide particles) injection. The waterline in
      small voxels was significantly more asymmetric at the tumor rim compared to the
      tumor center and normal muscle (P < 0.003). Composite images were synthesized,
      with the intensity in each voxel determined by the Fourier component (FC) of the
      water resonance having the greatest relative image contrast at that position. We
      tested whether regions with high contrast in FC images (FCIs) contain vasculature
      by comparing FCIs with CE-MRI as the "gold standard" of vascular density. The
      FCIs had 75% +/- 13% sensitivity, 74% +/- 10% specificity, and 91% +/- 4%
      positive predictive value (PPV) for vasculature detection at the tumor rim. These
      results suggest that tumor microvasculature can be detected using HiSS imaging
      without the use of contrast agents.

PMID- 19165879
TI  - Lung morphology assessment using MRI: a robust ultra-short TR/TE 2D steady state
      free precession sequence used in cystic fibrosis patients.
AB  - To evaluate feasibility and diagnostic quality of ultra-short TR/TE two
      dimensional (2D) steady state free precession (SSFP) MRI for cystic fibrosis (CF)
      patients. We performed lung MRI at 1.5 Tesla in 20 CF-patients (6-17 years, 12
      males). Axial, coronal, and sagittal sections were acquired in inspiration and
      expiration with maximum breath-hold time 10 s. MR and CT images were scored using
      a modified Brody scoring system to assess bronchiectasis, mucous plugging,
      atelectasis/consolidations, and air trapping. All images were scored by two
      experienced observers. A complete MR investigation took maximally 15 min. Maximal
      breath-holds were only 10 s and well tolerated. MRI identified major
      bronchiectasis, mucous plugging and atelectasis. End-expiratory scans showed
      patches of parenchyma with reduced signal intensity that may corresponded to
      areas of trapped air on expiratory CT scans. This MRI protocol based on ultra
      short TR/TE 2D SSFP is quick and well tolerated and provides highly relevant
      imaging features as seen on CT in CF patients. Most importantly, the SNR of the
      expiratory scans enables to visualize air trapping. The preliminary results of
      this study suggest MRI as a noteworthy additional imaging tool for routine
      monitoring of CF patients.

PMID- 19165880
TI  - Human whole blood T2 relaxometry at 3 Tesla.
AB  - A precise understanding of human blood spin-spin relaxation is of major
      importance for numerous applications, particularly functional magnetic resonance
      imaging (fMRI), which is increasingly performed at 3 Tesla. It is well known that
      T2 measured from partially deoxygenated blood depends on the Carr-Purcell Meiboom
      Gill (CPMG) refocusing interval (tau180) and on blood oxygenation (Y), yet debate
      remains over the quantification of this phenomenon, primarily with respect to the
      accuracy of its characterization by the diffusion and fast two-site exchange
      models. In this study, a detailed characterization of the deoxygenation-induced
      T2 reduction in human whole blood, as well as a comprehensive assessment of the
      role of tau180, were performed at 3 T. The diffusion model was found to better
      fit the observed T2 behavior as compared with the exchange model. The estimated
      diffusion-model parameters suggest the T2 decay enhancement at 3 T is due to a
      linear increase in the magnitude of deoxygenation-induced field inhomogeneities
      with field strength. These findings also confirm the potential of tau180
      manipulation in measuring changes in venous blood volume.

PMID- 19165881
TI  - Simultaneous z-shim method for reducing susceptibility artifacts with multiple
      transmitters.
AB  - The signal loss susceptibility artifact is a major limitation in gradient-echo
      MRI applications. Various methods, including z-shim techniques and
      multidimensional tailored radio frequency (RF) pulses, have been proposed to
      mitigate the through-plane signal loss artifact, which is dominant in axial
      slices above the sinus region. Unfortunately, z-shim techniques require multiple
      steps and multidimensional RF methods are complex, with long pulse lengths.
      Parallel transmission methods were recently shown to be promising for improving
      B1 inhomogeneity and reducing the specific absorption rate. In this work, a novel
      method using time-shifted slice-select RF pulses is presented for reducing the
      through-plane signal loss artifact in parallel transmission applications. A
      simultaneous z-shim is obtained by concurrently applying unique time-shifted
      pulses on each transmitter. The method is shown to reduce the signal loss
      susceptibility artifact in gradient-echo images using a four-channel parallel
      transmission system at 3T.

PMID- 19165882
TI  - Selective resonance suppression 1H-[13C] NMR spectroscopy with asymmetric
      adiabatic RF pulses.
AB  - Despite obvious improvements in spectral resolution at high magnetic field, the
      detection of 13C labeling by 1H-[13C] NMR spectroscopy remains hampered by
      spectral overlap, such as in the spectral region of 1H resonances bound to C3 of
      glutamate (Glu) and glutamine (Gln), and C6 of N-acetylaspartate (NAA). The aim
      of this study was to develop, implement, and apply a novel 1H-[13C] NMR
      spectroscopic editing scheme, dubbed "selective Resonance suppression by
      Adiabatic Carbon Editing and Decoupling single-voxel STimulated Echo Acquisition
      Mode" (RACED-STEAM). The sequence is based on the application of two asymmetric
      narrow-transition-band adiabatic RF inversion pulses at the resonance frequency
      of the 13C coupled to the protons that need to be suppressed during the mixing
      time (TM) period, alternating the inversion band downfield and upfield from the
      13C resonance on odd and even scans, respectively, thus suppressing the detection
      of 1H resonances bound to 13C within the transition band of the inversion pulse.
      The results demonstrate the efficient suppression of 1H resonances bound to C3 of
      Glu and Gln, and C4 of Glu, which allows the 1H resonances bound to C6 of NAA and
      C4 of Gln to be revealed. The measured time course of the resolved labeling into
      NAA C6 with the new scheme was consistent with the slow turnover of NAA.

PMID- 19165883
TI  - Parallel spectroscopic imaging reconstruction with arbitrary trajectories using k
      space sparse matrices.
AB  - Parallel imaging reconstruction has been successfully applied to magnetic
      resonance spectroscopic imaging (MRSI) to reduce scan times. For undersampled k
      space data on a Cartesian grid, the reconstruction can be achieved in image
      domain using a sensitivity encoding (SENSE) algorithm for each spectral data
      point. Alternative methods for reconstruction with undersampled Cartesian k-space
      data are the SMASH and GRAPPA algorithms that do the reconstruction in the k
      space domain. To reconstruct undersampled MRSI data with arbitrary k-space
      trajectories, image-domain-based iterative SENSE algorithm has been applied at
      the cost of long computing times. In this paper, a new k-space domain-based
      parallel spectroscopic imaging reconstruction with arbitrary k-space trajectories
      using k-space sparse matrices is applied to MRSI with spiral k-space
      trajectories. The algorithm achieves MRSI reconstruction with reduced memory
      requirements and computing times. The results are demonstrated in both phantom
      and in vivo studies. Spectroscopic images very similar to that reconstructed with
      fully sampled spiral k-space data are obtained at different reduction factors.

PMID- 19165884
TI  - Axial black blood turbo spin echo imaging of the right ventricle.
AB  - Black blood turbo spin echo (TSE) imaging of the right ventricle (RV) free wall
      is highly sensitive to cardiac motion, frequently resulting in nondiagnostic
      images. Temporal and spatial parameters of a black blood TSE pulse sequence were
      evaluated for visualization of the RV free wall. Seventy-four patient studies
      were retrospectively evaluated for the effects of acquisition timing on image
      quality. Axial black blood TSE images were acquired on 10 healthy volunteers to
      assess the role of spatial misregistration on right ventricle visualization;
      increasing the double inversion recovery (DIR) slice thickness beyond 300% had no
      effect on image quality (P = 0.2). Thirty-five patient studies were prospectively
      evaluated with inversion times (TIs) corresponding to the mid-diastolic rest
      period and end-systole based on visual analysis of a four chamber cine. When TIs
      were chosen to be within the patients' RV rest period, mean image quality score
      was significantly improved (2.3 vs 1.86; P < 0.001) and the number of clinically
      diagnostic images increased from 32% to 46%. Black blood TSE imaging of the RV
      free wall is highly sensitive to cardiac motion. Image quality can be improved by
      choosing TIs concordant with the rest period of the patient's RV that may occur
      at mid-diastole or end-systole.

PMID- 19165885
TI  - Electrodynamic constraints on homogeneity and radiofrequency power deposition in
      multiple coil excitations.
AB  - The promise of increased signal-to-noise ratio and spatial/spectral resolution
      continues to drive MR technology toward higher magnetic field strengths. SAR
      management and B1 inhomogeneity correction become critical issues at the high
      frequencies associated with high field MR. In recent years, multiple coil
      excitation techniques have been recognized as potentially powerful tools for
      controlling specific absorption rate (SAR) while simultaneously compensating for
      B1 inhomogeneities. This work explores electrodynamic constraints on transmit
      homogeneity and SAR, for both fully parallel transmission and its time
      independent special case known as radiofrequency shimming. Ultimate intrinsic SAR
      -the lowest possible SAR consistent with electrodynamics for a particular
      excitation profile but independent of transmit coil design--is studied for
      different field strengths, object sizes, and pulse acceleration factors. The
      approach to the ultimate intrinsic limit with increasing numbers of finite
      transmit coils is also studied, and the tradeoff between homogeneity and SAR is
      explored for various excitation strategies. In the case of fully parallel
      transmission, ultimate intrinsic SAR shows flattening or slight reduction with
      increasing field strength, in contradiction to the traditionally cited quadratic
      dependency, but consistent with established electrodynamic principles.

PMID- 19165886
TI  - Phosphatidylserine decarboxylases, key enzymes of lipid metabolism.
AB  - Phosphatidylserine decarboxylases (PSDs) (E.C. 4.1.1.65) are enzymes which
      catalyze the formation of phosphatidylethanolamine (PtdEtn) by decarboxylation of
      phosphatidylserine (PtdSer). This enzymatic activity has been identified in both
      prokaryotic and eukaryotic organisms. PSDs occur as two types of proteins
      depending on their localization and the sequence of a conserved motif. Type I
      PSDs include enzymes of eukaryotic mitochondria and bacterial origin which
      contain the amino acid sequence LGST as a characteristic motif. Type II PSDs are
      found in the endomembrane system of eukaryotes and contain a typical GGST motif.
      These characteristic motifs are considered as autocatalytic cleavage sites where
      proenzymes are split into alpha- and beta-subunits. The S-residue set free by
      this cleavage serves as an attachment site of a pyruvoyl group which is required
      for the activity of the enzymes. Moreover, PSDs harbor characteristic binding
      sites for the substrate PtdSer. Substrate supply to eukaryotic PSDs requires
      lipid transport because PtdSer synthesis and decarboxylation are spatially
      separated. Targeting of PSDs to their proper locations requires additional
      intramolecular domains. Mitochondrially localized type I PSDs are directed to the
      inner mitochondrial membrane by N-terminal targeting sequences. Type II PSDs also
      contain sequences in their N-terminal extensions which might be required for
      subcellular targeting. Lack of PSDs causes various defects in different cell
      types. The physiological relevance of these findings and the central role of PSDs
      in lipid metabolism will be discussed in this review.

PMID- 19165887
TI  - Fetal rhabdomyoma of the lower extremity.
AB  - We report a rare case of cellular fetal rhabdomyoma in a 9-year-old male, in the
      unusual location of right lower thigh. These tumors are more common in the head
      and neck region; and this case the second such case to be reported in the thigh.
      Fetal rhabdomyoma is a benign tumor of the skeletal muscle, showing varying
      degrees of skeletal muscle maturation. The present report discusses the
      histopathological features, the differential diagnosis and the importance of
      making the correct diagnosis for proper management of this rare entity.

PMID- 19165888
TI  - Developmental genes and cancer in children.
AB  - Childhood tumours are associated with congenital abnormalities suggesting that
      disruption of normal developmental processes may be linked with oncogenesis.
      Genetic and environmental exposures may combine to disrupt critical epigenetic
      processes during development, thus affecting gene-related signalling pathways and
      cellular function. This review examines the role of critical genes and processes
      regulating development such as the polycomb family and sonic hedgehog (SHH) as
      well as the Wnt signalling pathways and epigenetic variations (Snf5), methylation
      and loss of heterozygosity in controlling homeotic gene transcription and
      intracellular chromatin structure. The developmental and perinatal periods
      appears important as a window of opportunity for cancer research.

PMID- 19165889
TI  - Does the time-point of relapse influence outcome in pediatric rhabdomyosarcomas?
AB  - BACKGROUND: Childhood rhabdomyosarcoma (RMS), a soft tissue malignant tumor of
      skeletal muscle origin, accounts for approximately 3.5% of the cases of cancer
      among children 0-14 years and 2% of the cases among adolescents and young adults
      15-19 years of age. PROCEDURE: We evaluated survival (SUR) after first relapse
      depending on the time to relapse (TTR) in RMSs of childhood and adolescence.
      Early, intermediate, and late relapsing patients were evaluated for prognostic
      risk factors. RESULTS: Two hundred thirty-four patients with RMS enrolled in the
      German sarcoma trial CWS-81, CWS-86, CWS-91, and CWS-96 met selection criteria.
      Of the 234 patients, 35%, 32%, and 33% relapsed within 6 (early), 6-12
      (intermediate), and more than 12 (late) months respectively after the end of
      primary therapy. Four-year SUR was 12%, 21%, and 41% for early, intermediate, and
      late relapse respectively (P < 0.001). Four-year SUR after local relapse was 18%
      (early), 38% (intermediate), and 49% (late). Embryonal RMS showed four year SUR
      of 16%, 30%, and 46% (P < 0.001) whereas alveolar histology showed four year SUR
      of 8%, 6%, and 23% (P < 0.01) for early, intermediate, and late relapse
      respectively. CONCLUSION: TTR has significant influence on prognosis in relapsed
      RMS. It influences SUR independent of other features such as type of relapse,
      histology, tumor site, primary treatment time or irradiation in primary
      treatment.

PMID- 19165890
TI  - Controversies in the diagnosis and management of childhood acute immune
      thrombocytopenic purpura.
AB  - Acute immune thrombocytopenic purpura (ITP) occurs most commonly in young
      children who present with severe isolated thrombocytopenia and purpura. A marrow
      examination is not required unless glucocorticoids are used, lest treatment mask
      incipient acute lymphoblastic leukemia, but controversy exists here. The
      recommendations for evaluation and management remain controversial, since
      prospective controlled trials have not been done. There is some consensus based
      on experience and empiric data. Almost all children with acute ITP will recover
      completely without therapy. Although the various treatments may increase the
      platelet count, they do not influence the outcome of the illness, may increase
      cost, and cause significant side effects. Therefore, careful observation may be
      the best management option for the patient with ITP, in the absence of severe
      bleeding. The data available relevant to these issues are discussed.

PMID- 19165891
TI  - Obesity and metabolic changes are common in young childhood brain tumor
      survivors.
AB  - BACKGROUND: A population based cross-sectional study was used to examine the
      prevalence of metabolic syndrome and its components in childhood brain tumor
      survivors. PROCEDURE: Fifty-two survivors were examined at a mean age of 14.4
      years (range 3.8-28.7). Lipid and glucose metabolism, thyroid function, and
      plasma uric acid were evaluated. Fat mass and fat percentage were assessed by
      dual-energy X-ray absorptiometry (DXA). Metabolic syndrome was defined on
      International Diabetes Federation criteria. RESULTS: Ten (19%) patients were
      overweight and four (8%) were obese. According to DXA, 16/46 (35%) patients were
      obese. Central obesity was found in 11 (21%) patients. Cranial irradiation,
      hypothalamic/hypophyseal damage, growth hormone (GH) deficiency and impaired
      mobility were associated with overweight/obesity and central obesity. Thirteen
      (25%) subjects had hypercholesterolemia, 14 (27%) had raised low-density
      lipoprotein cholesterol (LDL-C), 12 (23%) had raised blood pressure, four (8%)
      had metabolic syndrome, two (4%) had hyperinsulinemia and five (10%) had
      hyperuricemia. Cranial irradiation was associated with hypercholesterolemia (P =
      0.019), raised LDL-C (P = 0.028), raised blood pressure (P = 0.040), and
      metabolic syndrome (P = 0.018). Impaired mobility was associated with
      hypercholesterolemia (P = 0.034). Hypothalamic/hypophyseal damage was associated
      with metabolic syndrome (P = 0.003) and hyperuricemia (P = 0.011) as was GH
      deficiency (P = 0.034 and P = 0.008). GH supplementation alleviated adverse
      metabolic outcomes among brain tumor survivors with GH deficiency. CONCLUSIONS:
      Obesity/overweight, dyslipidemia, hypertension, metabolic syndrome, and
      hyperuricemia were common in young childhood brain tumor survivors. Cranial
      irradiation, hypothalamic/hypophyseal damage, growth hormone deficiency, and/or
      impaired mobility were associated with higher risk for obesity and metabolic
      changes among these patients.

PMID- 19165892
TI  - Objective response of multiply recurrent low-grade gliomas to bevacizumab and
      irinotecan.
AB  - BACKGROUND: Chemotherapy has taken on a prominent role in the treatment of
      pediatric low-grade gliomas not amenable to gross total resections; however,
      there are few proven effective options for children with multiply recurrent
      tumors. Bevacizumab, a humanized immunoglobulin, monoclonal antibody that
      inhibits the activity of vascular endothelial growth factor and irinotecan have
      been used with some success in adults with malignant gliomas. METHODS: Ten
      children with multiply recurrent low-grade gliomas were treated with the
      combination of bevacizumab and irinotecan. Patients received treatment at a
      median of 5.2 years of age, range 1.5-11.1 years. The majority had diencephalic
      tumors, three had neurofibromatosis type 1, and two had disseminated disease at
      the time of treatment. Nine of 10 patients had progressed after three or greater
      chemotherapy regimens and one also had received radiation therapy. RESULTS: Seven
      patients had an objective neuroradiographic response, which was a complete
      response in one, partial response in three, and minor response in three. Clinical
      improvements were noted in seven, including improved visual acuity (2), improved
      motor function (2), weight gain in four with a diencephalic syndrome, and
      reversal of psychomotor retardation (3). Dose-limiting toxicities included
      transient leukoencephalopathy (1) and grade 3 protienuria (1). Response was
      durable in the majority of patients and six remain on treatment, for up to 22
      months. CONCLUSIONS: Multiply recurrent low-grade gliomas in children are
      responsive to the combination of bevacizumab and irinotecan. The drug combination
      has been relatively well tolerated, including in patients with neurofibromatosis
      type 1, and warrants further study.

PMID- 19165893
TI  - Convolution kernel design and efficient algorithm for sampling density
      correction.
AB  - Sampling density compensation is an important step in non-cartesian image
      reconstruction. One of the common techniques to determine weights that compensate
      for differences in sampling density involves a convolution. A new convolution
      kernel is designed for sampling density attempting to minimize the error in a
      fully reconstructed image. The resulting weights obtained using this new kernel
      are compared with various previous methods, showing a reduction in reconstruction
      error. A computationally efficient algorithm is also presented that facilitates
      the calculation of the convolution of finite kernels. Both the kernel and the
      algorithm are extended to 3D.

PMID- 19165894
TI  - Water channel proteins (later called aquaporins) and relatives: past, present,
      and future.
AB  - Water channels or water channel proteins (WCPs) are transmembrane proteins that
      have a specific three-dimensional structure with a pore that can be permeated by
      water molecules. WCPs are large families (over 450 members) that are present in
      all kingdoms of life. The first WCP was discovered in the human red blood cell
      (RBC) membrane in 1980s. In 1990s other WCPs were discovered in plants,
      microorganisms, various animals, and humans; and it became obvious that the WCPs
      belong to the superfamily of major intrinsic proteins (MIPs, over 800 members).
      WCPs include three subfamilies: (a) aquaporins (AQPs), which are water specific
      (or selective water channels); (b) aquaglyceroporins (and glycerol facilitators),
      which are permeable to water and/or other small molecules; and (c)
      "superaquaporins" or subcellular AQPs. WCPs (and MIPs) have several structural
      characteristics which were better understood after the atomic structure of some
      MIPs was deciphered. The structure-function relationships of MIPs expressed in
      microorganisms (bacteria, archaea, yeast, and protozoa), plants, and some
      multicellular animal species [nematodes, insects, fishes, amphibians, mammals
      (and humans)] are described. A synthetic overview on the WCPs from RBCs from
      various species is provided. The physiological roles of WCPs in kidney,
      gastrointestinal system, respiratory apparatus, central nervous system, eye,
      adipose tissue, skin are described, and some implications of WCPs in various
      diseases are briefly presented. References of detailed reviews on each topic are
      given. This is the first review providing in a condensed form an overview of the
      whole WCP field that became in the last 20 years a very hot area of research in
      biochemistry and molecular cell biology, with wide and increasing implications.

PMID- 19165895
TI  - Mitochondrial potassium channels.
AB  - Mitochondrial potassium channels are believed to contribute to cytoprotection of
      injured cardiac and neuronal tissues. The following potassium channels have been
      described in the inner mitochondrial membrane: the ATP-regulated potassium
      channel, the large conductance Ca(2+)-activated potassium channel, the voltage
      gated Kv1.3 potassium channel, and the twin-pore domain TASK-3 potassium channel.
      The putative functional roles of these channels include changes in mitochondrial
      matrix volume, mitochondrial respiration, and membrane potential. In addition,
      the activity of these channels modulates the generation of reactive oxygen
      species by mitochondria. In this article, we discuss recent observations on three
      fundamental issues concerning mitochondrial potassium channels: (i) their
      molecular identity, (ii) their interaction with potassium channel openers and
      inhibitors, and (iii) their functional properties.

PMID- 19165896
TI  - Structural studies of conotoxins.
AB  - Conotoxins are small disulfide-rich peptides from the venoms of marine cone
      snails. They target a variety of ion channels, transporters, and receptors
      besides the interest in their natural functions in venoms and they are of much
      interest as drug leads. This short article gives an overview of the structural
      diversity of conotoxins, and illustrates this diversity with recent selected
      examples of conotoxin structures.

PMID- 19165897
TI  - Temporal stability of adaptive 3D radial MRI using multidimensional golden means.
AB  - Breast tumor diagnosis requires both high spatial resolution to obtain
      information about tumor morphology and high temporal resolution to probe the
      kinetics of contrast uptake. Adaptive sampling of k-space allows images in
      dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) to be
      reconstructed at various spatial or temporal resolutions from the same dataset.
      However, conventional radial approaches have limited flexibility that restricts
      image reconstruction to predetermined resolutions. Golden-angle radial k-space
      sampling achieves flexibility in-plane with samples that are incremented by the
      golden angle, which fills two-dimensional (2D) k-space with radial spokes that
      have a relatively uniform angular distribution for any time interval. We extend
      this method to three-dimensional (3D) radial sampling, or 3D-Projection
      Reconstruction (3D-PR) using multidimensional golden means, which are derived
      from modified Fibonacci sequences by an eigenvalue approach. We quantitatively
      compare this technique to conventional 3D radial methods in terms of the
      fluctuation in error caused by undersampling artifacts, and show that the golden
      3D-PR method can substantially improve the temporal stability of quantitative
      measurements made from dynamic images when compared to conventional 3D radial
      approaches of k-space sampling.

PMID- 19165899
TI  - Whole-brain single-shot STEAM DTI at 4 Tesla utilizing transverse coherences for
      enhanced SNR.
AB  - Diffusion tensor imaging is an important method for noninvasively acquiring
      structural information of the human brain. For advanced fiber tracking, the
      acquisition of diffusion-weighted (DW) images has to be performed along many
      different spatial directions, resulting in long scan times. Therefore, the ultra
      fast imaging method, echo-planar imaging (EPI), is mostly used, but this
      technique suffers from susceptibility-induced image artefacts and geometric
      distortions. These problems become even more pronounced at very high magnetic
      field strengths. In this regard, DW, single-shot STEAM is an interesting and
      rapid imaging alternative to EPI-based methods. DW single-shot STEAM enables the
      acquisition of artefact-free images albeit at the expense of a reduced signal-to
      noise ratio (SNR), which can be compensated by utilizing high magnetic fields.
      Here, the application of DW single-shot STEAM at 4 Tesla is demonstrated. To
      optimize the SNR and the resolution properties, a new variable flip-angle
      computational algorithm is introduced enabling accurate signal evolution
      computation with a precise calculation of transverse coherences. Omission of
      radiofrequency (RF) spoiling results in an approximate twofold increase of the DW
      signal by integration of the stable refocused transverse magnetization. The
      advantage of the approach is shown in simulations and in vivo experiments.

PMID- 19165898
TI  - Quantitative magnetization transfer measured pool-size ratio reflects optic nerve
      myelin content in ex vivo mice.
AB  - Optic nerves from mice that have undergone retinal ischemia were examined using a
      newly implemented quantitative magnetization transfer (qMT) technique. Previously
      published results indicate that the optic nerve from retinal ischemia mice
      suffered significant axon degeneration without detectable myelin injury at 3 days
      after reperfusion. At this time point, we acquired ex vivo qMT parameters from
      both shiverer mice (which have nearly no myelin) and control mice that have
      undergone retinal ischemia, and these qMT measures were compared with diffusion
      tensor imaging (DTI) results. Our findings suggests that the qMT estimated ratio
      of the pool sizes of the macromolecular and free water protons reflected the
      different myelin contents in the optic nerves between the shiverer and control
      mice. This pool size ratio was specific to myelin content only and was not
      significantly affected by the presence of axon injury in mouse optic nerve 3 days
      after retinal ischemia.

PMID- 19165900
TI  - Genetic polymorphisms in the thioredoxin 2 (TXN2) gene and risk for spina bifida.
AB  - TXN2 encodes human thioredoxin 2, a small redox protein important in cellular
      antioxidant defenses, as well as in the regulation of apoptosis. Txn2 knockout
      mice fail to complete neural tube closure by E10.5 and die in utero. We
      hypothesized that genetic variation in human TXN2 gene may alter the function of
      the encoded protein in a manner associated with an increased risk for neural tube
      defects (NTDs). A DNA re-sequencing effort of the human TXN2 gene was taken.
      After a variation in the promoter was identified, the transcriptional activity of
      different alleles was investigated. The possible association between these
      variations and the risk of spina bifida was further evaluated in a subset of
      samples obtained from a large population-based case-control study in California
      in two different ethnicity groups, non-Hispanic white and Hispanic white. We
      identified a novel promoter insertion polymorphism located 9 base pairs upstream
      of the transcription start site of exon 1(-9 insertion). The GA, G and GGGA
      insertions were associated with a marked decrease of transcriptional activity
      when overexpressed in both U2-OS (an osteosarcoma cell line) and 293 cells
      (derived from human embryonic kidney). Further analysis revealed that the GA
      insertion was associated with increased spina bifida risk for Hispanic whites.
      Our study revealed a novel Ins/Del polymorphism in the human TXN2 gene proximal
      promoter region that altered the transcriptional activity and is associated with
      spina bifida risk. This polymorphism may be a genetic modifier of spina bifida
      risk in this California population.

PMID- 19165901
TI  - A multispectral three-dimensional acquisition technique for imaging near metal
      implants.
AB  - Metallic implants used in bone and joint arthroplasty induce severe spatial
      perturbations to the B0 magnetic field used for high-field clinical magnetic
      resonance. These perturbations distort slice-selection and frequency encoding
      processes applied in conventional two-dimensional MRI techniques and hinder the
      diagnosis of complications from arthroplasty. Here, a method is presented whereby
      multiple three-dimensional fast-spin-echo images are collected using discrete
      offsets in RF transmission and reception frequency. It is demonstrated that this
      multi acquisition variable-resonance image combination technique can be used to
      generate a composite image that is devoid of slice-plane distortion and possesses
      greatly reduced distortions in the readout direction, even in the immediate
      vicinity of metallic implants.

PMID- 19165902
TI  - Comparison of hypercapnia-based calibration techniques for measurement of
      cerebral oxygen metabolism with MRI.
AB  - MRI may be used to measure fractional changes in cerebral oxygen metabolism via a
      metabolic model. One step commonly used in this measurement is calibration with
      image data acquired during hypercapnia, which is a state of increased CO2 content
      of the blood. In this study some commonly used hypercapnia-inducing stimuli were
      compared to assess their suitability for the calibration step. The following
      stimuli were investigated: (a) inspiration of a mixture of 4% CO2, 21% O2 and
      balance N2; (b) 30-s breath holding; and (c) inspiration of a mixture of 4% CO2
      and 96% O2 (i.e., carbogen). Measurements of BOLD and cerebral blood flow made on
      nine subjects during the different hypercapnia-inducing stimuli showed that each
      stimulus leads to a different calibration of the model. We argue that of the
      aforementioned stimuli, inspiration of 4% CO2, 21% O2 and balance N2 should be
      preferred for the calibration as the other stimuli produce responses that violate
      assumptions of the metabolic model.

PMID- 19165903
TI  - PARACEST MRI with improved temporal resolution.
AB  - PARAmagnetic Chemical Exchange Saturation Transfer (PARACEST) is a novel contrast
      mechanism for MRI. A PARACEST MRI methodology with high temporal resolution is
      highly desired for in vivo MRI applications of molecular imaging. To address this
      need, a strategy has been developed that includes a long selective saturation
      period before each repetition of a Rapid Acquisition with Relaxation Enhancement
      (RARE) pulse sequence. This strategy is suitable for the application of PARACEST
      contrast agents to environments with long T1 relaxation times. An alternative
      strategy uses short selective saturation periods before the acquisition of each k
      space trajectory to maintain steady state conditions, which can be implemented
      with a Fast Low Angle Shot (FLASH) pulse sequence. These short saturation periods
      lengthen the total scan time as compared to the first approach but compensate for
      the loss in PARACEST contrast related to T1 relaxation. Both approaches have been
      demonstrated in vitro and in vivo with significantly improved temporal
      resolutions as compared to a conventional gradient-echo PARACEST method without
      sacrificing CNR efficiency. These demonstrations also adopted a strategy for
      measuring the PARACEST effect that only requires selective saturation at a single
      MR frequency, which further improves temporal resolution for PARACEST detection.

PMID- 19165904
TI  - Proceedings of the 9th Symposium on Catecholamines and Other Neurotransmitters in
      Stress, June 16-21, 2007, Smolenice Castle, Slovakia.

PMID- 19165905
TI  - Pyridoxal phosphate dependency, a newly recognized treatable catastrophic
      epileptic encephalopathy.

PMID- 19165906
TI  - Inside Gaza's Al-Shifa hospital.

PMID- 19165907
TI  - Proceedings from the First q-bio Conference on Cellular Information Processing,
      August 8-11, 2007, Santa Fe, New Mexico, USA.

PMID- 19165908
TI  - NEUROTOX 24. Proceedings of the 24th International Neurotoxicology Conference,
      November 11-14, 2007, San Antonio, Texas, USA.

PMID- 19165909
TI  - [Magistral lecture: The National Institute of Cardiology: 30 years in Tlalpan].

PMID- 19165910
TI  - Salaries of ED managers stop climbing, as hospitals respond to financial
      pressures.

PMID- 19165911
TI  - Where's the list?

PMID- 19165912
TI  - Hands on!

PMID- 19165913
TI  - Back to basics in Berlin.
AB  - At this year's quinquennial International Congress of Genetics, human genetics
      provided only a fascinating minority of the content of this conference dedicated
      to illuminating fundamental biological systems and their evolution.

PMID- 19165915
TI  - Casting a wider net for diabetes susceptibility genes.

PMID- 19165914
TI  - Variation in KLK genes, prostate-specific antigen and risk of prostate cancer.

PMID- 19165916
TI  - Hedgehog in Wnterland.

PMID- 19165917
TI  - Psychiatric genetics gets a boost.

PMID- 19165918
TI  - Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease influenced by genetic
      and environmental factors. We carried out a genome-wide association scan and
      replication study and found an association between SLE and a variant in TNFAIP3
      (rs5029939, meta-analysis P = 2.89 x 10(-12), OR = 2.29). We also found evidence
      of two independent signals near TNFAIP3 associated with SLE, including one
      previously associated with rheumatoid arthritis (RA). These results establish
      that variants near TNFAIP3 contribute to differential risk of SLE and RA.

PMID- 19165919
TI  - Multiple polymorphisms in the TNFAIP3 region are independently associated with
      systemic lupus erythematosus.
AB  - The TNFAIP3 (tumor necrosis factor alpha-induced protein 3) gene encodes a
      ubiquitin editing enzyme, A20, that restricts NF-kappaB-dependent signaling and
      prevents inflammation. We show that three independent SNPs in the TNFAIP3 region
      (rs13192841, rs2230926 and rs6922466) are associated with systemic lupus
      erythematosus (SLE) among individuals of European ancestry. These findings
      provide critical links between A20 and the etiology of SLE.

PMID- 19165920
TI  - Mutations of CASK cause an X-linked brain malformation phenotype with
      microcephaly and hypoplasia of the brainstem and cerebellum.
AB  - CASK is a multi-domain scaffolding protein that interacts with the transcription
      factor TBR1 and regulates expression of genes involved in cortical development
      such as RELN. Here we describe a previously unreported X-linked brain
      malformation syndrome caused by mutations of CASK. All five affected individuals
      with CASK mutations had congenital or postnatal microcephaly, disproportionate
      brainstem and cerebellar hypoplasia, and severe mental retardation.

PMID- 19165921
TI  - Detection of sharing by descent, long-range phasing and haplotype imputation.
AB  - Uncertainty about the phase of strings of SNPs creates complications in genetic
      analysis, although methods have been developed for phasing population-based
      samples. However, these methods can only phase a small number of SNPs effectively
      and become unreliable when applied to SNPs spanning many linkage disequilibrium
      (LD) blocks. Here we show how to phase more than 1,000 SNPs simultaneously for a
      large fraction of the 35,528 Icelanders genotyped by Illumina chips. Moreover,
      haplotypes that are identical by descent (IBD) between close and distant
      relatives, for example, those separated by ten meioses or more, can often be
      reliably detected. This method is particularly powerful in studies of the
      inheritance of recurrent mutations and fine-scale recombinations in large sample
      sets. A further extension of the method allows us to impute long haplotypes for
      individuals who are not genotyped.

PMID- 19165922
TI  - Evolutionary toggling of the MAPT 17q21.31 inversion region.
AB  - Using comparative sequencing approaches, we investigated the evolutionary history
      of the European-enriched 17q21.31 MAPT inversion polymorphism. We present a
      detailed, BAC-based sequence assembly of the inverted human H2 haplotype and
      compare it to the sequence structure and genetic variation of the corresponding
      1.5-Mb region for the noninverted H1 human haplotype and that of chimpanzee and
      orangutan. We found that inversion of the MAPT region is similarly polymorphic in
      other great ape species, and we present evidence that the inversions occurred
      independently in chimpanzees and humans. In humans, the inversion breakpoints
      correspond to core duplications with the LRRC37 gene family. Our analysis favors
      the H2 configuration and sequence haplotype as the likely great ape and human
      ancestral state, with inversion recurrences during primate evolution. We show
      that the H2 architecture has evolved more extensive sequence homology, perhaps
      explaining its tendency to undergo microdeletion associated with mental
      retardation in European populations.

PMID- 19165923
TI  - Max-independent functions of Myc in Drosophila melanogaster.
AB  - Myc proteins are powerful proto-oncoproteins and important promoters of growth
      and proliferation during normal development. They are thought to exercise their
      effects upon binding to their partner protein Max, and their activities are
      largely antagonized by complexes of Max with Mnt or an Mxd family protein.
      Although the biological functions of Myc, Mxd and Mnt have been intensively
      studied, comparatively little is known about the in vivo role of Max. Here we
      generate Max loss-of-function and reduction-of-function mutations in Drosophila
      melanogaster to address the contribution of Max to Myc-dependent growth control.
      We find that many biological activities of Myc do not, or only partly, require
      the association with Max--for example, the control of endoreplication and cell
      competition-and that a Myc mutant that does not interact with Max retains
      substantial biological activity. We further show that Myc can control RNA
      polymerase III independently of Max, which explains some of Myc's observed
      biological activities. These studies show the ability of Myc to function
      independently of Max in vivo and thus change the current model of Max network
      function.

PMID- 19165924
TI  - Genome-wide association study identifies ANXA11 as a new susceptibility locus for
      sarcoidosis.
AB  - Sarcoidosis is a complex chronic inflammatory disorder with predominant
      manifestation in the lung. In the first genome-wide association study (> 440,000
      SNPs) of this disease, comprising 499 German individuals with sarcoidosis and 490
      controls, we detected a series of genetic associations. The strongest association
      signal maps to the ANXA11 (annexin A11) gene on chromosome 10q22.3. Validation in
      an independent sample (1,649 cases, 1,832 controls) confirmed the association
      (SNP rs2789679: P = 3.0 x 10(-13), rs7091565: P = 1.0 x 10(-5), allele-based
      test). Extensive fine mapping located the association signal to a region between
      exon 5 and exon 14 of ANXA11. A common nonsynonymous SNP (rs1049550, C > T,
      [corrected] R230C) was found to be strongly associated with sarcoidosis. The GWAS
      lead SNP and additional risk variants in the region (rs1953600, rs2573346,
      rs2784773) were in strong linkage disequilibrium with rs1049550. Annexin A11 has
      complex and essential functions in several biological pathways, including
      apoptosis and proliferation.

PMID- 19165925
TI  - Deletion polymorphism upstream of IRGM associated with altered IRGM expression
      and Crohn's disease.
AB  - Following recent success in genome-wide association studies, a critical focus of
      human genetics is to understand how genetic variation at implicated loci
      influences cellular and disease processes. Crohn's disease (CD) is associated
      with SNPs around IRGM, but coding-sequence variation has been excluded as a
      source of this association. We identified a common, 20-kb deletion polymorphism,
      immediately upstream of IRGM and in perfect linkage disequilibrium (r2 = 1.0)
      with the most strongly CD-associated SNP, that causes IRGM to segregate in the
      population with two distinct upstream sequences. The deletion (CD risk) and
      reference (CD protective) haplotypes of IRGM showed distinct expression patterns.
      Manipulation of IRGM expression levels modulated cellular autophagy of
      internalized bacteria, a process implicated in CD. These results suggest that the
      CD association at IRGM arises from an alteration in IRGM regulation that affects
      the efficacy of autophagy and identify a common deletion polymorphism as a likely
      causal variant.

PMID- 19165926
TI  - A common sequence motif associated with recombination hot spots and genome
      instability in humans.
AB  - In humans, most meiotic crossover events are clustered into short regions of the
      genome known as recombination hot spots. We have previously identified DNA motifs
      that are enriched in hot spots, particularly the 7-mer CCTCCCT. Here we use the
      increased hot-spot resolution afforded by the Phase 2 HapMap and novel search
      methods to identify an extended family of motifs based around the degenerate 13
      mer CCNCCNTNNCCNC, which is critical in recruiting crossover events to at least
      40% of all human hot spots and which operates on diverse genetic backgrounds in
      both sexes. Furthermore, these motifs are found in hypervariable minisatellites
      and are clustered in the breakpoint regions of both disease-causing nonallelic
      homologous recombination hot spots and common mitochondrial deletion hot spots,
      implicating the motif as a driver of genome instability.

PMID- 19165927
TI  - Pathological responses to oncogenic Hedgehog signaling in skin are dependent on
      canonical Wnt/beta3-catenin signaling.
AB  - Constitutive Hedgehog (Hh) signaling underlies several human tumors, including
      basal cell carcinoma (BCC) and basaloid follicular hamartoma in skin.
      Intriguingly, superficial BCCs arise as de novo epithelial buds resembling
      embryonic hair germs, collections of epidermal cells whose development is
      regulated by canonical Wnt/beta-catenin signaling. Similar to embryonic hair
      germs, human BCC buds showed increased levels of cytoplasmic and nuclear beta
      catenin and expressed early hair follicle lineage markers. We also detected
      canonical Wnt/ beta-catenin signaling in epithelial buds and hamartomas from mice
      expressing an oncogene, M2SMO, leading to constitutive Hh signaling in skin.
      Conditional overexpression of the Wnt pathway antagonist Dkk1 in M2SMO-expressing
      mice potently inhibited epithelial bud and hamartoma development without
      affecting Hh signaling. Our findings uncover a hitherto unknown requirement for
      ligand-driven, canonical Wnt/ beta-catenin signaling for Hh pathway-driven
      tumorigenesis, identify a new pharmacological target for these neoplasms and
      establish the molecular basis for the well-known similarity between early
      superficial BCCs and embryonic hair germs.

PMID- 19165928
TI  - A developmental framework for dissected leaf formation in the Arabidopsis
      relative Cardamine hirsuta.
AB  - The developmental basis for the generation of divergent leaf forms is largely
      unknown. Here we investigate this problem by studying processes that distinguish
      development of two related species: Arabidopsis thaliana, which has simple
      leaves, and Cardamine hirsuta, which has dissected leaves with individual
      leaflets. Using genetics, expression studies and cell lineage tracing, we show
      that lateral leaflet formation in C. hirsuta requires the establishment of growth
      foci that form after leaf initiation. These growth foci are recruited at the leaf
      margin in response to activity maxima of auxin, a hormone that polarizes growth
      in diverse developmental contexts. Class I KNOTTED1-like homeobox (KNOX) proteins
      also promote leaflet initiation in C. hirsuta, and here we provide evidence that
      this action of KNOX proteins is contingent on the ability to organize auxin
      maxima via the PINFORMED1 (PIN1) auxin efflux transporter. Thus, differential
      deployment of a fundamental mechanism polarizing cellular growth contributed to
      the diversification of leaf form during evolution.

PMID- 19165929
TI  - Pay for performance.

PMID- 19165930
TI  - Diagnostic accuracy of digital photography and image analysis for the measurement
      of foot conformation in the horse.
AB  - REASONS FOR PERFORMING STUDY: Rigorous evaluation of practicable methods for the
      objective assessment of foot conformation has not been performed. OBJECTIVES: To
      assess the practicability, precision and accuracy of the process of obtaining
      measurements of horses' feet using photography and image processing software.
      METHODS: Precision study: Lateral photographs of horses' feet were obtained twice
      by 2 veterinary surgeons (image acquisition - IAc). Photographs were analysed by
      2 masked veterinary surgeons on 2 occasions (image analysis - IAn). Measurements
      were compared within and between operators for self and non-self acquired
      photographs. Agreement indices (AIs) and 95% limits of agreement (LOA) were
      calculated for the IAn process alone and for the combined IAc + IAn processes.
      Accuracy study: Measurements obtained from lateral photographs were compared with
      those obtained from lateromedial radiographs. AIs and 95% LOA were calculated for
      each measurement. RESULTS: Precision study: Mean intra- and interoperator AIs for
      the IAn process alone were > or = 0.90 while those for the combined IAc + IAn
      processes were > or = 0.89 for all measurements. Similar mean AIs and 95% LOA
      were calculated regardless of image origin. The 95% LOA for hoof angle, heel
      height/toe height% and coronary band angle for all comparisons were within target
      values. Accuracy study: Mean AIs were > or = 0.89 for all measurements. The 95%
      LOA for heel height/toe height% and coronary band angle were within target
      values. CONCLUSIONS: Excellent precision was identified within and between
      operators regardless of image origin. High levels of accuracy were also
      identified, especially for heel height/toe height% and coronary band angle,
      indicating that photography and radiography may be used interchangeably.
      POTENTIAL RELEVANCE: Acquisition and analysis of photographic images is an
      appropriate method for the objective measurement of foot conformation, both in
      clinical and, research settings.

PMID- 19165931
TI  - Implications of different degrees of arytenoid cartilage abduction on equine
      upper airway characteristics.
AB  - REASON FOR PERFORMING STUDY: The necessary degree of arytenoid cartilage
      abduction (ACA) to restore airway patency at maximal exercise has not been
      determined. OBJECTIVES: Use computational fluid dynamics modelling to measure the
      effects of different degrees of ACA on upper airway characteristics of horses
      during exercise. HYPOTHESIS: Maximal ACA by laryngoplasty is necessary to restore
      normal peak airflow and pressure in Thoroughbred racehorses with laryngeal
      hemiplegia. METHODS: The upper airway was modeled with the left arytenoid in 3
      different positions: maximal abduction; 88% cross-sectional area of the rima
      glottis; and 75% cross-sectional area of the rima glottis. The right arytenoid
      cartilage was maximally abducted. Two models were assumed: Model 1: no
      compensation of airway pressures; and Model 2: airway pressure compensation
      occurs to maintain peak airflow. The cross-sectional pressure and velocity
      distributions for turbulent flow were studied at peak flow and at different
      positions along the airway. RESULTS: Model 1: In the absence of a change in
      driving pressure, 12 and 25% reductions in cross-sectional area of the larynx
      resulted in 4.11 and 5.65% reductions in peak airflow and 3.68 and 5.64% in tidal
      volume, respectively, with mild changes in wall pressure. Model 2: To maintain
      peak flow, a 6.27% increase in driving tracheal pressure was required to
      compensate for a cross-sectional reduction of 12% and a 13.63% increase in
      driving tracheal pressure was needed for a cross-sectional area reduction of 25%.
      This increase in negative driving pressure resulted in regions with low
      intraluminal and wall pressures, depending on the degree of airway diameter
      reduction. CONCLUSION: Assuming no increase in driving pressure, the decrease in
      left ACA reduced airflow and tidal volume. With increasing driving pressure, a
      decrease in left ACA changed the wall pressure profile, subjecting the
      submaximally abducted arytenoid cartilage and adjacent areas to airway collapse.
      CLINICAL RELEVANCE: The surgical target of ACA resulting in 88 % of maximal cross
      sectional area seems to be appropriate.

PMID- 19165932
TI  - Early pathogenesis of equine Streptococcus equi infection (strangles).
AB  - REASONS FOR PERFORMING STUDY: Little is known about entry and subsequent
      multiplication of Streptococcus equi following exposure of a susceptible horse.
      This information would have value in design of intranasal vaccines and
      understanding of shedding and protective immune responses. OBJECTIVES: To
      determine entry points and sites of subsequent replication and dispersion of S.
      equi at different times after intranasal infection or commingling exposure.
      METHODS: Previously unexposed horses and ponies were subjected to euthanasia 1,
      3, 20 or 48 h following intranasal inoculation with biotin labelled or unlabelled
      S. equi CF32. Some ponies were inoculated with suspensions of equal numbers of
      CF32 and its mutants lacking capsule, S. equi M-like protein or streptolysin S.
      Others were infected by commingling exposure and subjected to euthanasia after
      onset of fever. Tonsils and lymph nodes were cultured for S. equi and tissues
      sectioned for histopathological examination and fluorescent microscopy. RESULTS:
      Tonsillar tissues of both the oro- and nasopharynx served as portals of entry.
      Entry was unexpectedly rapid but involved few bacteria. Small numbers of
      organisms were detected in tonsillar crypts, in adjacent subepithelial follicular
      tissue and draining lymph nodes 3 h after inoculation. By 48 h, clumps of S. equi
      were visible in the lamina propria. At onset of fever, tonsillar tissues and one
      or more mandibular and retropharyngeal lymph nodes were heavily infiltrated by
      neutrophils and long chains of extracellular S. equi. Mutant S. equi lacking
      virulence factors were not seen in draining lymph nodes. CONCLUSIONS: Although
      very small numbers of S. equi entered the lingual and nasopharyngeal tonsils,
      carriage to regional lymph nodes occurred within hours of inoculation. This
      observation, together with visual evidence of intracellular and extracellular
      multiplication of S. equi in tonsillar lymphoid tissue and lymph nodes over the
      following days, indicates involvement of potent antiphagocytic activity and
      failure of innate immune defences. RELEVANCE: Future research should logically
      address the tonsillar immune mechanisms involved including identification of
      effector cell(s) and antigens.

PMID- 19165934
TI  - Days lost from training by two- and three-year-old Thoroughbred horses: a survey
      of seven UK training yards.
AB  - REASONS FOR PERFORMING STUDY: The first major epidemiological study of injury
      incidence in the UK flat racing Thoroughbred (TB), published in 1985, found
      lameness to be the single largest reason for days when horses failed to train. It
      was considered advisable to ascertain if progress has been made in reducing the
      problem of musculoskeletal injuries in the intervening period. OBJECTIVE: To
      quantify injury incidence and days lost from training by 2- and 3-year-old TBs in
      UK training yards during 2002 and 2003. METHODS: One-hundred-and-eighty-two
      yearling TBs were recruited at the end of 2001 and daily training and injury
      records maintained over the following 2 training and racing seasons. Days were
      defined as lost from training when a horse failed to train at a slow canter speed
      or faster, and could be assigned to one of 4 categories: lameness, medical,
      traumatic and unknown. The incidence and number of days lost due to specific
      injuries and medical conditions was determined by further subdividing the
      lameness and medical categories. RESULTS: The study period provided a total of
      52,601 2-year-old and 29,369 3-year-old days available for training, with 2-year
      olds failing to train on a significantly greater proportion of days available
      than 3-year-olds. Lameness was the most important condition causing horses to
      miss training, with stress fractures being the most important cause of lameness.
      Medical conditions were a relatively minor cause of days lost from training,
      accounting for approximately 5% of untrained days in the 2 age groups.
      CONCLUSIONS: In UK flat racehorses there has been little change in the proportion
      of days lost from training due to lameness over the last 20 years. POTENTIAL
      RELEVANCE: This study highlights the need for further efforts to reduce the
      problem of lameness in the racing TB.

PMID- 19165933
TI  - OB-cadherin cloning and expression in a model of wound repair in horses.
AB  - REASON FOR PERFORMING STUDY: Horses suffer from a debilitating impediment in
      repairing wounds located on the lower limb that leads to the development of a
      fibroproliferative disorder (exuberant granulation tissue). This condition is a
      source of wastage since it often forces retirement from competition. Treatments
      that resolve or prevent this condition are still lacking, maybe due to deficient
      knowledge of the underlying molecular mechanisms. Fibroblast-to-myofibroblast
      conversion is an essential step allowing contraction during wound repair and is
      accompanied by an increase in OB-cadherin expression. OBJECTIVES: To clone equine
      cadherin-11 (CDH11) cDNA and to study its spatiotemporal expression profile
      during the repair of body and limb wounds, thereby contributing to a better
      understanding of the repair process. METHODS: Cloning was by a PCR technique.
      Expression was studied in intact skin and in 1, 2, 3, 4 and 6-week-old wounds of
      the body and limb. Temporal CDH11 gene expression was determined by RT-PCR while
      OB-cadherin protein expression was mapped immunohistochemically. RESULTS: Equine
      CDH11 is a highly conserved gene and protein. mRNA was not expressed in equine
      skin whereas the wound repair process was characterised by a significantly higher
      expression in the thorax than in limb samples. mRNA expression pattern was
      paralleled by protein data as confirmed by immunohistochemistry. CONCLUSIONS: The
      data suggest that deficient OB-cadherin expression in the first phases of wound
      repair contributes to the excessive proliferative response seen in horse limb
      wounds. POTENTIAL RELEVANCE: Future studies should verify the quantitative,
      temporal expression of this protein in order to provide the basis for targeted
      therapies that might prevent the development of EGT in horse wound repair.

PMID- 19165935
TI  - Pharmacokinetics of carbetocin, a long-acting oxytocin analogue, following
      intravenous administration in horses.
AB  - REASON FOR PERFORMING STUDY: Current therapy protocols to treat persistent post
      mating endometritis and retained fetal membranes in mares typically include the
      administration of ecbolic drugs. Evaluation of the pharmacokinetics and
      tolerability of carbetocin, a long-acting oxytocin analogue, after i.v.
      administration is required. OBJECTIVES: To determine the pharmacokinetic
      parameters (principally half-life) of carbetocin in horses. METHODS: Five mature
      mares and one gelding received 0.175 mg carbetocin i.v. All animals were
      monitored periodically throughout the study for elevation in rectal temperature,
      heart rate, respiratory rate and signs of pain or discomfort. Plasma samples were
      collected for determination of carbetocin concentrations by radioimmunoassay.
      RESULTS: Administration of carbetocin was well tolerated by all horses and its
      half-life was 17.2 min. CONCLUSIONS: The half-life of carbetocin is greater than
      that previously reported for oxytocin (6.8 min). POTENTIAL RELEVANCE: Carbetocin
      is an attractive alternative to oxytocin therapy in broodmare management.

PMID- 19165936
TI  - Histological and ultrastructural evidence that recurrent laryngeal neuropathy is
      a bilateral mononeuropathy limited to recurrent laryngeal nerves.
AB  - REASONS FOR PERFORMING STUDY: Recurrent laryngeal neuropathy (RLN) is a common
      and debilitating peripheral nerve disease of horses, but it remains unclear if
      this disease is a mono- or polyneuropathy. An understanding of the distribution
      of the neuropathological lesions in RLN affected horses is fundamental to
      studying the aetiology of this very significant disease of tall horses.
      OBJECTIVE: To determine whether RLN should be classified as a mono- or
      polyneuropathy. METHODS: Multiple long peripheral nerves and their innervated
      muscles were examined systematically in 3 clinically affected RLN horses RESULTS:
      Severe lesions were evident in the left as well as right recurrent laryngeal
      nerves in all horses, both distally and, in one case, also proximally. No primary
      axonal lesions were evident in other nerves nor were changes found in their
      innervated muscles. CONCLUSIONS: RLN is not a polyneuropathy but should be
      classified as a bilateral mononeuropathy. POTENTIAL RELEVANCE: Genetic and local
      factors specifically affecting the recurrent laryngeal nerves in RLN-affected
      horses should now be investigated further.

PMID- 19165937
TI  - The effects of maternal health and body condition on the endocrine responses of
      neonatal foals.
AB  - REASONS FOR PERFORMING THE STUDY: Chronic and acute alterations in maternal
      nutrient intake during pregnancy alter pancreatic and hypothalamo-pituitary
      adrenal (HPA) axis function in the offspring, before and after birth. Little is
      known about these effects. OBJECTIVE: To determine whether maternal nutrient
      restriction caused by natural infection with Streptococcus equi altered endocrine
      function in neonatal foals born from mares fed a maintenance or high plane of
      nutrition throughout pregnancy. METHODS: Ten primiparous mares received either a
      diet to maintain moderate body condition score (Moderate, n = 5) or a near ad
      libitum feeding regime to maintain a high body condition score (High, n = 5)
      throughout pregnancy. All mares inadvertently became infected with Streptococcus
      equi in mid gestation and lost approximately 10% body mass. RESULTS: Maternal
      insulin and glucose concentrations decreased (P < 0.05) during, and one month
      following, the weight loss period. High mares weighed more (P < 0.05) at
      parturition than Moderate mares; all foals were healthy. Gestational age, foal
      bodyweights, placental and clinical parameters after birth were no different
      between the 2 groups. Foal plasma cortisol and glucose responses to exogenous
      adrenocorticotrophic hormone and insulin, respectively, were similar for both
      groups. Insulin concentrations during glucose tolerance test were significantly
      higher (P < 0.05) in foals from Moderate than High mares and compared with foals
      studied previously from healthy, well-fed mares, suggesting that the beta cell
      sensitivity to glucose was enhanced in Moderate. CONCLUSION: Acute nutrient
      restriction in mid gestation caused by maternal illness and inappetence,
      superimposed on a maintenance feed intake throughout pregnancy, enhanced insulin
      secretion to glucose in foals. Nutritional programming of pancreatic beta cells,
      but not the HPA axis, appeared to depend on the level of nutrition before and
      after the weight loss period. POTENTIAL RELEVANCE: Disturbances in neonatal
      pancreatic beta cell function programmed during pregnancy may predispose foals to
      metabolic problems in later life.

PMID- 19165938
TI  - Accuracy of the TurfTrax Racing Data System for determination of equine speed and
      position.
AB  - REASONS FOR PERFORMING STUDY: The speed and position data collected by TurfTrax
      Racing Data Limited during UK Thoroughbred racing have potential to benefit
      equine science and welfare. The size (the 2006 data set alone consists of 30,932
      individual horse starts across 2667 races) and nature (speed and 2D position for
      each horse at 4 updates per second) of the data make it a unique resource for
      questions in equine safety, welfare, performance, and animal locomotion.
      OBJECTIVE: To determine the accuracy of the TurfTrax tracking system in
      estimating the speed and position of horses during racing. METHODS: Measurements
      from the TurfTrax wireless tracking system were compared with those of a survey
      grade global positioning system (GPS) receiver. RESULTS: The TurfTrax system was
      found to give position measurements to within +/- 11 and +/- 64 cm in the fore
      aft and lateral directions, respectively, averaging +/- 38 cm (interquartile
      range) and speed to within 0.15 m/s. POTENTIAL RELEVANCE: The data collected by
      the TurfTrax system are of sufficient accuracy to inform new diagnoses, training
      regimens and basic locomotor scientific studies. The position data can provide
      the precise distance, going, inclination, rate of turn and pack positioning
      through which each horse has raced. The speed profile can be used to examine the
      level of exertion, effect of training regimens and influence of racecourse
      features on performance. A first clinical application would be to analyse
      retrospectively these factors on occurrence of injury to compare with past
      training regimens, levels of exertion, and/or racecourse conditions.

PMID- 19165939
TI  - Deep erosions of the palmar aspect of the navicular bone diagnosed by standing
      magnetic resonance imaging.
AB  - REASONS FOR PERFORMING STUDY: Erosion of the palmar (flexor) aspect of the
      navicular bone is difficult to diagnose with conventional imaging techniques.
      OBJECTIVES: To review the clinical, magnetic resonance (MR) and pathological
      features of deep erosions of the palmar aspect of the navicular bone. METHODS:
      Cases of deep erosions of the palmar aspect of the navicular bone, diagnosed by
      standing low field MR imaging, were selected. Clinical details, results of
      diagnostic procedures, MR features and pathological findings were reviewed.
      RESULTS: Deep erosions of the palmar aspect of the navicular bone were diagnosed
      in 16 mature horses, 6 of which were bilaterally lame. Sudden onset of lameness
      was recorded in 63%. Radiography prior to MR imaging showed equivocal changes in
      7 horses. The MR features consisted of focal areas of intermediate or high signal
      intensity on T1-, T2*- and T2-weighted images and STIR images affecting the
      dorsal aspect of the deep digital flexor tendon, the fibrocartilage of the palmar
      aspect, subchondral compact bone and medulla of the navicular bone. On follow-up,
      7/16 horses (44%) had been subjected to euthanasia and only one was being worked
      at its previous level. Erosions of the palmar aspect of the navicular bone were
      confirmed post mortem in 2 horses. Histologically, the lesions were characterised
      by localised degeneration of fibrocartilage with underlying focal osteonecrosis
      and fibroplasia. The adjacent deep digital flexor tendon showed fibril formation
      and fibrocartilaginous metaplasia. CONCLUSIONS: Deep erosions of the palmar
      aspect of the navicular bone are more easily diagnosed by standing low field MR
      imaging than by conventional radiography. The lesions involve degeneration of the
      palmar fibrocartilage with underlying osteonecrosis and fibroplasia affecting the
      subchondral compact bone and medulla, and carry a poor prognosis for return to
      performance. POTENTIAL RELEVANCE: Diagnosis of shallow erosive lesions of the
      palmar fibrocartilage may allow therapeutic intervention earlier in the disease
      process, thereby preventing progression to deep erosive lesions.

PMID- 19165940
TI  - Epidemiological study design and the advancement of equine health.
AB  - The primary purposes of epidemiological investigations are to learn about causal
      mechanisms related to disease incidence and identify factors for therapy and
      prevention. Epidemiological studies can be observational--further categorised as
      descriptive or analytical--or experimental. Investigators performing experimental
      studies, or randomised controlled trials (RCTs), randomly assign treatments or
      exposures to study participants for the expressed purpose of the study. The most
      frequently encountered observational epidemiological studies employed to
      investigate issues of equine health are cohort, case-control, cross-sectional and
      case series. A cohort study is an investigation in which the researcher follows
      (observes) a group, termed the cohort, over time to measure incidence of a
      particular outcome. A case-control study is an investigation in which the
      researcher selects a group of affected individuals (cases) and a comparison group
      (controls) to investigate factors associated with being a case. A cross-sectional
      study investigates a group of individuals for study that is often defined by
      membership in a target population and data concerning outcome and exposure are
      either collected related to the same time-point or data are collected by
      investigators at the same time. Case series are descriptive studies used to
      generate hypotheses concerning predictors of disease or recovery that can be
      performed retrospectively or prospectively. The best evidence for clinical
      practice is often derived from patient-centred observational epidemiological
      studies and it is imperative that equine veterinarians become familiar with study
      designs for the appropriate interpretation of epidemiological findings.

PMID- 19165941
TI  - Management of the national programme to eradicate equine infectious anaemia from
      Ireland during 2006: a review.

PMID- 19165942
TI  - An outbreak of equine infectious anaemia in Ireland during 2006: investigation
      methodology, initial source of infection, diagnosis and clinical presentation,
      modes of transmission and spread in the Meath cluster.

PMID- 19165943
TI  - An outbreak of equine infectious anaemia in Ireland during 2006: the modes of
      transmission and spread in the Kildare cluster.

PMID- 19165944
TI  - Clinical trials using a telemetric endoscope for use during over-ground exercise:
      a preliminary study.
AB  - Dynamic collapse of the upper respiratory tract (URT) is a common cause of poor
      performance in horses. These conditions occur predominantly during strenuous
      exercise when the URT is unable to maintain dilation in the face of high
      inspiratory pressures. In most cases, these disorders cannot be accurately
      diagnosed during a resting endoscopic examination. To date, a definitive
      diagnosis of dynamic URT obstructions has been possible only by performing an
      endoscopic examination during high-speed treadmill exercise. However, recent
      technological advances now enable URT endoscopy to be performed while the horse
      is exercising in its normal environment.

PMID- 19165945
TI  - Medical facilities under intense pressure in Gaza.

PMID- 19165946
TI  - On the shifting boundaries of medicine.

PMID- 19165947
TI  - Proceedings of the 8th International Symposium on Chromosome Aberrations, 2007.

PMID- 19165948
TI  - Psychological challenges of surviving cancer.  Transitions are particularly
      tough; some problems emerge at unexpected times.

PMID- 19165950
TI  - Phone psychotherapy for depression.

PMID- 19165949
TI  - Preventing driving accidents involving teenagers.  Behavioral strategies parents
      can use to reduce their children's risk of injury or death.

PMID- 19165951
TI  - The value of long-term psychodynamic psychotherapy.

PMID- 19165952
TI  - Update on Usher syndrome.
AB  - PURPOSE OF REVIEW: The present review addresses the mechanisms, genetics and
      pathogenesis of Usher syndrome. RECENT FINDINGS: Recent molecular findings have
      provided more information regarding the pathogenesis of this disorder and the
      wide phenotypic variation in both audiovestibular and/or visual systems. Evidence
      has begun to emerge supporting a theory of a protein interactome involving the
      Usher proteins in both the inner ear and the retina. This interactome appears to
      be important for hair cell development in the ear but its role in the retina
      remains unclear. SUMMARY: Understanding clinical disease progression and
      molecular pathways is important in the progress towards developing gene therapy
      to prevent blindness due to Usher syndrome as well as delivering prognostic
      information to affected individuals.

PMID- 19165953
TI  - Visual hallucinations in eye disease.
AB  - PURPOSE OF REVIEW: The literature related to visual hallucinations in
      ophthalmological settings from 2007 to 2008 is presented as a review of recent
      developments and trends. RECENT FINDINGS: Acuity, contrast sensitivity, age and
      sex emerge as significant and consistent risk factors for visual hallucinations,
      together with new evidence to suggest that up to 40% of patients have long-term
      hallucinations. Scotoma size and specific eye pathology do not influence
      hallucination risk. Induced hallucinations in normal individuals provide a model
      for those in eye disease, revealing a shift in thalamocortical circuitry and
      neurophysiological links to states of drowsy wakefulness. Serotonergic therapy
      emerges as a potential treatment. Two ophthalmological interventions are added to
      the list of procedures provoking hallucinations. Historical accounts of Charles
      Bonnet, his syndrome and two novel visual syndromes highlight ongoing
      difficulties of case definition and the wider clinical context in which visual
      hallucinations occur. SUMMARY: Current research into visual hallucination is
      predominantly ophthalmology-led, with increasing recognition of the phenomena,
      their prevalence and prognosis within the specialty. Deafferentation remains the
      best available pathophysiological account, although it fails to explain the
      absence of hallucinations in the majority of patients with eye disease. Whether
      hallucinations require treatment and, if so, what that treatment should be
      remains unclear.

PMID- 19165954
TI  - Medically unexplained visual loss in adult patients.
AB  - PURPOSE OF REVIEW: In this review, we discuss the investigation and management of
      patients with visual loss that cannot be accounted for by organic pathology.
      RECENT FINDINGS: Because visual loss in these patients often has a psychosocial
      basis, we do not like the term 'medically unexplained visual loss' as a
      diagnostic label. 'Unexplained visual loss' is a useful working diagnosis until
      occult pathology is excluded and a positive diagnosis of functional visual loss
      (FVL) can be established. Recent literature highlights the utility and
      limitations of visually evoked potentials in estimating objective visual acuity.
      Multifocal electroretinography and ocular coherence tomography are invaluable in
      revealing occult macular pathology that may not be apparent to clinical
      examination and full-field electroretinography testing. Cortical visual loss can
      be mistaken for FVL. There is still no evidence base to guide our management of
      patients with FVL. However, useful insights can be gained from the literature on
      functional symptoms in other specialties. SUMMARY: Making the diagnosis of FVL
      demands vigilance but is important to do. It should mark not just the end of
      investigation, but the start of treatment. More research is needed to see if
      treatments used in other functional disorders work in FVL.

PMID- 19165955
TI  - The diagnosis and management of supraaortic arterial dissections.
AB  - PURPOSE OF REVIEW: To review recent advances in understanding supraaortic
      arterial dissections and their diagnosis and management. RECENT FINDINGS:
      Dissection of the supraaortic arteries, including the extracranial carotid and
      vertebral arteries and intracranial arteries, is increasingly identified as an
      important cause of stroke and subarachnoid hemorrhage. The most common cause
      likely involves minor trauma with preexisting arteriopathy. The imaging diagnosis
      of dissection is complicated by the wide range of pathological changes that occur
      after dissection. Modalities include ultrasound, magnetic resonance imaging and
      angiography, computed tomography angiography, and digital subtraction
      angiography. The choice of method is best tailored to each patient individually.
      Similarly, treatments may vary from antiplatelet medications to complex
      endovascular techniques. There are limited data to guide treating patients with
      strokes due to arterial dissections. Conservative management is likely optimal
      for most patients with cervical dissections, endovascular treatments being
      reserved for the rapidly deteriorating patient only. However, patients with
      subarachnoid hemorrhage due to rupture of a dissecting aneurysm require urgent
      endovascular or surgical treatment of the aneurysm. SUMMARY: The diagnosis and
      management of supraaortic arterial dissections is complex, and a variable
      multidisciplinary approach will likely yield the best outcome.

PMID- 19165956
TI  - Incidental intracranial aneurysms: rationale for treatment.
AB  - PURPOSE OF REVIEW: The review critically appraises the available evidence and
      current rationale for treating incidental intracranial aneurysms. RECENT
      FINDINGS: The rationale for treating incidental intracranial aneurysms uses
      comparisons between the so-called natural history, provided in a recent meta
      analysis, and risks of treatments. Some risk factors for ruptures were identified
      (age >60, female sex, size >5 mm, posterior circulation aneurysms), but study
      quality is poor and relative risks are modest, of borderline statistical
      significance. SUMMARY: The medical literature cannot provide reliable numerical
      data of sufficient precision and quality to feed mathematical models of
      prediction of potential treatment benefits. Hence, the rationale fails to justify
      increasingly used treatments. A different approach using randomized trials is now
      in order.

PMID- 19165957
TI  - Combination therapy of levosulpiride and   lamotrigine associated with tardive
      dyskinesia.

PMID- 19165958
TI  - Systemic failure of orthodox psychiatry.

PMID- 19165959
TI  - Leading the response to a notifiable disease.

PMID- 19165960
TI  - Self-execution, capital punishment, and the economics of murder: analysis of U.K.
      statistics suggests that suicide by murder suspects is not influenced by the
      probability of execution.

PMID- 19165961
TI  - Progress: poverty or prosperity? joining the debate between George and Marshall
      on the effects of economic growth on the distribution of income.

PMID- 19165962
TI  - A long time between murders.

PMID- 19165963
TI  - Loving and hating Simone Weil.

PMID- 19165964
TI  - The uncertain art: grave robbing.

PMID- 19165965
TI  - [Luis de Molina and black slavery].

PMID- 19165966
TI  - Outbreak news.  Yellow fever, Guinea.

PMID- 19165967
TI  - Meeting of the Diarrhoeal and Enteric Vaccines Advisory Committee, October 2008-
      executive summary.

PMID- 19165968
TI  - A manifesto against femicide.

PMID- 19165969
TI  - Wetland drainage and agricultural transformations in the southern highlands of
      Papua New Guinea.

PMID- 19165971
TI  - Lessons learned from co-ordinating a group health education workshop for Pacific
      people.

PMID- 19165972
TI  - Re: helmets not helpful--an example of poor public policy.

PMID- 19165973
TI  - Positive coronary artery remodelling detected by IVUS after stent implantation
      for ST elevation myocardial infarction.

PMID- 19165974
TI  - [Update on tissue engineering: propagation of regenerative medicine for bone and
      cartilage].

PMID- 19165976
TI  - Cold snap and norovirus equals tough Christmas.

PMID- 19165977
TI  - Will the PCT split benefit nursing?

PMID- 19165979
TI  - 'Let's make the most of those Christmas shifts'.

PMID- 19165978
TI  - Nurses in management must champion the profession's potential to advance care.

PMID- 19165980
TI  - Caring with cosmetics.

PMID- 19165981
TI  - Why we need older nurses.

PMID- 19165982
TI  - How christmas festivities and pressures can damage health and well-being.

PMID- 19165983
TI  - Manual handling 1--assisted stand. The manual handling procedure to help a seated
      patient into a standing position.

PMID- 19165984
TI  - Understanding the differences between moisture lesions and pressure ulcers.
AB  - This one-part unit discusses the difference between pressure ulcers and moisture
      lesions. It explores the causes of these skin problems and highlights the need
      for patient care plans to reflect the underlying cause of the problem.

PMID- 19165985
TI  - Using couple and family therapy to treat people experiencing alcohol problems.
AB  - This article outlines the introduction of systemic psychotherapeutic
      interventions for couples and families who are experiencing problems with
      alcohol. It explains the background to this therapeutic approach and the outcomes
      for clients. Systemic therapy is now used by the team as an integral part of the
      mainstream clinical programme within the alcohol treatment service.

PMID- 19165986
TI  - Views of healthcare staff and mothers about postnatal depression screening.
AB  - BACKGROUND: More research is needed on views of using the Edinburgh Postnatal
      Depression Scale to screen recent mothers for this condition. AIM: To examine
      healthcare professionals' and mothers' views of using this tool. METHOD: Findings
      of two qualitative studies on screening for postnatal depression were compared to
      provide an overview. RESULTS: There were differences in views within and between
      groups, although all practitioners found the tool helpful for introducing the
      topic. Symptom disclosure was an issue for all, although practitioners were
      unaware that some mothers feared their child would be taken into care.
      CONCLUSION: Pragmatic reasons (such as lack of time and resources) meant practice
      was not always optimal but, if recommendations are followed, mothers may be
      encouraged to disclose symptoms.

PMID- 19165987
TI  - Are techniques used for intramuscular injection based on research evidence?
AB  - The technique for delivering intramuscular injection remains rooted in custom and
      practice. This literature review examines the evidence on this commonly performed
      nursing procedure covering all aspects including site and needle selection.

PMID- 19165988
TI  - A colorful past.

PMID- 19165989
TI  - Possible effects of the proposed Highmark/IBC consolidation.

PMID- 19165990
TI  - Greed and fear on steriods.

PMID- 19165991
TI  - History of the dental profession.

PMID- 19165992
TI  - So you want to be a dentist? An investigative report.
AB  - The purpose of this study was to identify a testing mechanism that could predict
      a student's hand skills performance if they chose a career in dentistry. Hand eye
      coordination is an important developmental skill required to navigate the
      rigorous dental school curriculum. These skills traditionally were assessed by
      using a carving chalk block exercise. This "gold standard" for determining a
      student's digital dexterity was used for many years in dental education. We
      postulated that a survey could take the place of chalk carving and still be a
      reliable predictor of a student's performance. A questionnaire was developed
      looking at a dental student's everyday activities and hobbies. We wanted to
      determine if a correlation could be made between hand-eye coordination activities
      and a student's preclinical grades. Analysis of the questionnaire given to ninety
      seven first year students at the University of Pennsylvania School of Dental
      Medicine showed a direct correlation between activities that students were
      involved in prior to beginning dental education and the quality of their
      preclinical dental skills. With insightful interpretation, the use of this type
      of questionnaire might help locate individuals that are suited for dentistry, and
      allow potential students to have greater confidence in choosing dentistry or a
      related field.

PMID- 19165993
TI  - Nursing that works happiness at work.

PMID- 19165994
TI  - Vitale measure to encourage nursing education advances.

PMID- 19165995
TI  - [Investigations on cordycepin production by solid culture of Cordyceps
      militaris].
AB  - An efficient method to produce cordycepin by solid culture using Cordyceps
      militaris was investigated in this study. Firstly, the changes of cordycepin
      during various growing periods of solid culture using 5 strains of C. militaris
      were detected, the best strain and optimal growing period for cordycepin
      production were determined. Then, by experiments of quadratic rotation-orthogonal
      combination design and orthogonal design, the medium composition and growth
      conditions for high yield of cordycepin were optimized. With the optimized method
      to produce cordycepin, the content of cordycepin in the medium was increased to
      0.60%, which was nearly 2 times higher than the highest yield reported.

PMID- 19165996
TI  - [Study on effect of drought stress on physiological adaptation of seedlings of
      Atractylodes lancea].
AB  - OBJECTIVE: To study the effect of drought stress on the changes of physiological
      adaptation of Atractylodes lancea seedlings. METHOD: Investigation was carried
      out on content changes of MDA, soluble protein, and activities of SOD, POD, CAT,
      APX in A. lancea seedlings under polyethylene glycol (PEG-6000)-simulated drought
      stress. RESULT: In A. lancea seedlings treated with 15% and 25% PEG, the content
      of MDA increased significantly with the stress time, and increased more
      significantly at a higher concentration of PEG. The content of soluble protein
      increased significantly after treatment on the day one and day three; activities
      of SOD, POD, CAT and APX increased at first and decreased later, increasing rates
      rose at high concentration of PEG moreover, activities of POD, APX reached the
      maximum after three days, and the time of maximum activities changed with
      concentration of PEG. CONCLUSION: A. lancea seedlings adapted to drought stress
      by increasing the content of soluble protein to decrease water potential, and by
      improving activities of protective enzymes to enhance anti-oxidative ability
      under drought stress.

PMID- 19165997
TI  - [Identification of Gynostemma from their adulterant Cayratia japonica by PCR
      RFLP].
AB  - OBJECTIVE: To establish a convenient and effective method for the identification
      of Gynostemma and Cayratia japonica. METHOD: Eight species, including Gynostemm
      pentaphyllum, G. pentagynum, G. cardiospermum, G. longipe, G. yixingense, G.
      laxiflorum, G. guangxiense and C. japonica were investigated through PCR - RFLP
      of six chloroplast DNA fragments. The six gene fragments were digested by six
      restriction endonuclease respectively, including Taq I, Hpa II, EcoR I, Rsa I,
      Hha I, Hind III. RESULT: Seven species of Gynostemma and their adulterant could
      be identified by trnK1f-trnK2r and Rsa. CONCLUSION: PCR - RFLP provides a quick,
      reliable molecular marker technique for identification of Cynostemma and their
      adulterant Cayratia japonica.

PMID- 19165998
TI  - [Establishment and optimization of sliver staining differential display of
      microtubers from Pinellia ternata in vitro].
AB  - OBJECTIVE: In this study, orthogonal design was used to optinize DDRT-PCR
      amplification system on Pinellia ternata microtubers in vitro in five factors
      four levels respectively. METHOD: P. ternata stems and microtubers in vitro were
      selected as explants. The effects of five kinds of factors were studied by
      orthogonal design method including emplate cDNA, Mg2+, dNTPs, primers and Taq DNA
      polymerase, and in order to establish the optimum DDRT-PCR system of P. ternata
      microtubers in vitro. RESULT AND CONCLUSION: A satisfactory DDRT-PCR technique
      system for P. ternata microtubers in vitro with desirable repeatability and
      polymorphic bands was established. In a total volume of 20 microL DDRT-PCR
      system, it contained 10 x buffer, 150 micromol L(-1) dNTPs, 2 micromol L(-1)
      anchor primer, 1 micromol L(-1) arbitrary primer, 2.5 mmol L(-1) Mg2+, 0.6 U Taq
      DNA polymerase and 2.5 microg template cDNA. The effect of the five factors was
      in sequence of Taq DNA polymerase > template cDNA > dNTPs > Mg2+ > Primers. The
      optimum DDRT-PCR system will provide scientific reference basis for studying
      effecting character of P. ternata microtubers associated with genes expression.

PMID- 19165999
TI  - [Research on optimization system on tissue culture and rapid propagation of
      Pueraria mirifica].
AB  - OBJECTIVE: To study the tissue culture and rapid-proliferation techniques of
      Pueraria mirifica. METHOD: The tender branch were used as explants and cultivated
      in different media. The optimum media for inducing buds, proliferation and
      rooting were selected by adjusting the kinds and doses of plant hormones and
      special compounds. RESULT: The medium of MS + IBA 0.05 mg L(-1) + BA 0.5 mg L(-1)
      was suitable for buds inducing and could be used in the first generation
      cultivation; MS + IBA 0. 02 mg L(-1) + BA 0.2 mg L(-1) and MS +BA 0.1 mg L(-1)
      were employed by turns in subculture, 25 days propagation coefficient was 3.0;
      and the medium of 1/2MS + IBA 0.1 mg L(-1) + IAA 0.2 mg L(-1) + C (special
      compound) 10 mg L(-1) was used for roots inducing, the rooting rate was 76.9%.
      Rooting plantlets were transplanted in spring and summer; the surviving rate was
      81.0%. CONCLUSION: This technique system could be employed for rapid propagation
      of P. mirifica.

PMID- 19166000
TI  - [Preliminary study on variation pattern of Cistanche deserticola].
AB  - OBJECTIVE: Through analyze of shape, structure and content of effective
      components of Cistanche deserticola, the variation of "you cong rong" is
      discussed. METHOD: The color surface, texture, the size of pith and the arrange
      of vascular bundle was observed with freshed, dried drugs and the transverse
      section, the effective component of echinacoside and acteoside was analyzed with
      hplc and the amylose was analyzed with ultraviolet spectrophotometry. RESULT: The
      variation of "you cong rong" is obvious different with the common drug in shape
      and structure, the content of echinacoside is 2.5 times, acteoside is 3.8 times,
      amylose yield is 1.6 times and the content is 2 times of the common drugs.
      CONCLUSION: "you cong rong" is an independent variation pattern of C.
      deserticola, it has no relationship with the ecological and geographical
      conditions.

PMID- 19166001
TI  - [Determination of loganin and paeonol in Liuwei Dihuang pills by HPLC amalgamated
      of double UV waves].
AB  - OBJECTIVE: To establish a high performance liquid chromatographic (HPLC)
      amalgamated to double UV waves method for simultaneous determination of loganin
      and paeonol in Liuwei Dihuang pills. METHOD: A HPLC method was developed. The
      separation was carried out on a Agilent Zorbax SB C18 column (5 microm, 4.6 mm x
      250 mm). The mobile phase consisted of water (A) and acetonitrile (B) with linear
      linear gradient elution [0-8 min, (B) from 1% to 12%; 8-21 min, B keep 12%; 21-40
      min, (B) from 12% to 90%; 40-50 min, B keep 90% for 10 min]. The detection was
      Photodiode Array with the detection wavelengths were at 236 nm and 274 nm. The
      column temperature being 30 degrees C and the flow rate was 1.0 mL min(-1).
      Extracting the chromatergraph from 274 nm and 236 nm, we amalgamated the two
      chromatographs by matlab programmed. RESULT: The calibration curves of loganin
      and paeonol were linear in the ranges of 0.0362-1.09 microg (r =0. 9998) and
      0.0450-1.35 microg (r =0.9998), respectively. The average recoveries of loganin
      and paeonol were 97.3% (RSD 1.4 %) and 103.0% (RSD 1.9%), respectively. Three
      different batches of Liuwei Dihuang pills were determined with this method.
      CONCLUSION: This is a more convenient, reasonable and credible quality control
      method for the traditional Chinese medicine.

PMID- 19166002
TI  - [Formulation optimization of controlled porosity osmotic-pump tablets of total
      paeony glycosides].
AB  - OBJECTIVE: To prepare controlled porosity osmotic-pump tablets of total paeony
      glycosides (TPG) and establish the relationship between formulation factors of
      membrane and drug release rate. METHOD: Uniform design was used to achieve the
      quantitative relationship between the release rate and formulation factors of
      membrane. Optimized prescription was calculated from the regression equation.
      RESULT: A significant correlation and a fine precision of the regession equation
      were obtained. Controlled porosity osmotic-pump tablets of TPG were prepared
      based on the calculations, and the drug release profile was in accord with zero
      order kinetics (r = 0.9902). CONCLUSION: Uniform design is a convenient and
      efficient approach for formulation optimization of controlled porosity osmotic
      pump tablets.

PMID- 19166003
TI  - [Effect of pectins of different degree of esterification on in-vitro sophoridine
      release of hydrophilic matrix tablets containing total alkaloids of Sophora
      alopecuroides].
AB  - OBJECTIVE: To prepare colon-targetting tablets of total alkaloids of Sophora
      alopecuroides and evaluate the effect of pectins of different degree of
      esterification (DE) on sophoridine release profiles in-vitro. METHOD: Wet
      granulation technique was employed to prepare petin-based matrix tablets, then
      tablets were coated the optimal formulation with Kollicoat MAE 30 DP based on the
      optimal formulation and analysed their release. RESULT: Coated formulation E
      could target total alkaloids of S. alopecuroides to colon and various DE of
      pectin exerted different effects on sophoridine release. The release of low DE
      pectin-based matrix tablets coating with Kollicoat MAE 30 DP approximatedly
      fitted zere-order eqution, which was erosion depended. CONCLUSION: Low DE pectin
      based matrix tablet coating with Kollicoat MAE 30 DP can deliver sophoridine to
      colon, hence improve the effectiveness of sophoridine.

PMID- 19166004
TI  - [Rapid determination of contents of hirudin's hydrolysates in processed leech by
      dot blotting].
AB  - OBJECTIVE: To determine the contents of hirudin's hydrolysates in processed
      leeches, set up a new evaluating method of dot blotting to evaluate the qualities
      of those processed Chinese medicines as leeches. METHOD: Contents of hirudin's
      hydrolysates in processed leeches were determined by dot blotting with rat
      antibody of anti-hirudin as the first antibody. Blotting signal was analyzed by
      software of Quantity One. RESULT: Contents of hirudin's hydrolysates in four
      batches of processed leeches were 296.51, 165.47, 95.58, and 298.05 microg g(-1),
      respectively. CONCLUSION: Difference among four batches of processed leeches was
      significant in the content of hirudin's hydrolysates. Dot blotting, as a
      convenient and accurate method can be broadly used for evaluating processed
      products of Chinese crude drugs similar to leeches.

PMID- 19166005
TI  - [Study on biligustilides from Angelica sinensis].
AB  - OBJECTIVE: To study the chemical constituents of Angelica sinensis. METHOD: The
      constituents were separated by chromatographic methods, and their structures were
      identified on the basis of spectroscopic analysis. RESULT: Eight compounds were
      isolated and identified as levistolide A (1), senkyunolide O (2), (3Z, 3Z')-6.8',
      7.3'-diligustilide (3), tokinolide B (4), isotokinolide B (5), (3'Z)-(3R, 8S,
      3a'R, 6'S)-3, 3a': 8, 6'-biligustilide (6), E, E'-3. 3', 8. 8'-diligustilide (7)
      and E, E'-3. 3', 8. 8'-isodiligustilide (8), which are all diligustilides.
      CONCLUSION: Compound 7 was obtained from the plant for the first time; compounds
      6 and 8 are new compounds.

PMID- 19166006
TI  - [Studies on chemical constituents of Ranunculus japonicus].
AB  - OBJECTIVE: To isolate and determine the chemical constituents of Ranunculus
      japonicus in Liupan Mountain, Ningxia province, China. METHOD: The herb was
      extracted with ethanol by ultrasonic bath. The extractives were divided to
      petroleum ether, ethyl acetate, n-butanol parts. The first two parts were
      separated and purified with silica gel and Sephadex LH -20 column chromatography.
      The structures of the separated compounds were idnetefied by physical and
      chemical properties and spectral analysis. RESULT: Nine compounds were isolated
      and identified as follows: scoparone (1), tricin (2), protocatechuic acid (3),
      luteolin (4), anemonin (5), scopoletin (6), 5-hydroxy-6, 7-dimethoxyflavone (7),
      ternatolide (8), 5-hydroxy-7, 8-dimethoxy-flavone (9). CONCLUSION: Compounds 1-9
      were isolated from Ranunculus japonicus for the first time.

PMID- 19166007
TI  - [Studies on chemical constituents of aerial parts of Ammopiptanthus mongolicus].
AB  - OBJECTIVE: To investigate the chemical constituents of the aerial parts of
      Ammopiptanthus mongolicus. METHOD: The chemical constituents were isolated by
      various column chromatographic methods. The structures were identified by
      spectral data. RESULT: Ten compounds were isolated and identified as m
      hydroxybenzoic acid (1), 1-(4-hydroxyphenyl) ethanone (2), beta-sitosterol (3), (
      )-syringaresinol (4), (+)-lariciresinol (5), blumenol A (6), blumenol B (7), beta
      daucosterol (8), coniferin (9), syringin (10). CONCLUSION: The ten compounds were
      obtained from the genus Ammopiptanthus for the first time.

PMID- 19166008
TI  - [Characterization of chemical components of essential oil from flowers of
      Chrysanthemum morifolium produced in Anhui province].
AB  - OBJECTIVE: To analyze the chemical components of the essential oil extracted from
      six cultivars' Juhua (Zaogongju, Wangongju, Huangyaoju, Chuju, Xiaoboju and
      Daboju) produced in Anhui province of China, which were breed from Chrysanthemum
      morifolium, and to provide scientific basis for quality control. METHOD: The
      essential oils of the six cultivars'Juhua were extracted by water-steam
      distillation and separated by GC capillary column chromatography. The components
      were quantitatively determined with normalization method, and identified by GC
      MS. RESULT: From Zaogongju, Wangongju, Huangyaoju, Chuju, Xiaoboju and Daboju,
      247, 226, 246, 182, 216 and 122 chromatographic peaks were detected, among them
      75, 54, 78, 50, 53 and 43 components were identified,which were composed of
      85.67%, 82.80%, 81.38%, 73.22%, 71.51% and 72.87% of the total essential oil,
      respectively. CONCLUSION: Monoterpenoid compounds were higher more than
      sesquiterpenoid compounds in the five juhua except for Chuju. There was no
      difference in the constituents of essential oil of Zaogongju and Wangongju. And
      verbenyl acetate was the main chemical constituent and composed of 32.10% and
      37.85% of the total essential oil, respectively. (1R)-Camphor and bisabolol oxide
      A were the main chemical constituents in Huangyaoju, which were composed of
      28.70% and 12.58% of the total essential oil, respectively. beta-Selinene and
      borneol were the main chemical constituents in Chuju, which were composed of
      17.85% and 12.84% of the total essential oil, respectively. Eucalyptol was the
      main chemical constituent in Xiaoboju, which were composed of 21.33%. Verbene
      oxides and chrysanthenone were composed of 25.32% and 8.26% of the total
      essential oil, respectively, in the Daboju. The common chemical constituents were
      camphene, borneol, bornyl aceate, (1R)-camphor, (-)-4-terpineol, alpha-terpineol,
      eucalyptol, cis-caryophyllene, caryophyllene oxide, juniper camphor, beta
      sesquiphellandrene, alpha-curcumene and beta-farnesene in the six cultivars'
      Juhua produced in Anhui province of China. The resultant data provided the
      further evidences to distinguish Juhua' cultivars and scientific basis for
      quality control of Juhua.

PMID- 19166009
TI  - [HPLC fingerprint analysis of cordyceps and mycelium of cultured cordy].
AB  - OBJECTIVE: To establish HPLC fingerprints of cordyceps and mycelium of cultured
      cordy for quality control. METHOD: The analysis was carried out on a Diamonsil
      C18 column eluted with phosphate buffer (pH 6.5) and methanol as mobile phase,
      the gradient elution program was used, and the detection wavelength was 260 nm;
      The similarity of fingerprints was evaluated, then, cluster analysis was studied.
      RESULT: The method of HPLC fingerprint analysis was validated and in keeping with
      the requirement. Ten common peaks were found in HPLC fingerprint. Cordyceps from
      different areas and mycelium of cultured cordy could be distinguished by the HPLC
      fingerprint. CONCLUSION: All results above exhibit that this method is
      practicable, reproducible, and reliable as a method for the quality control of
      cordyceps and mycelium of cultured cordy at present.

PMID- 19166010
TI  - [Simultaneous determination of four glycosylflavones from Lophatherum gracile by
      RP-HPLC].
AB  - OBJECTIVE: To develop a RP-HPLC method for simultaneous determination of
      orientin, isorientin, vitexin and isovitexin in Lophatherum gracile from
      different habitat and harvesting time. METHOD: The HPLC method was applied and
      the chromatographic column was a Waters XBridge C18 column (4.6 mm x 250 mm, 5
      microm). The mobile phase consisted of methanol-0.05% acetic acid (35:65). The
      flow rate was 1.0 mL min(-1) and the detection wavelength was set at 340 nm. The
      column temperature was set at 25 degrees C. RESULT: Four components were isolated
      well, the linear relationships were excellent. The mean recoveries and RSD values
      of orientin, isorientin, vitexin and isovitexin were 103.2%, 2.1%; 101.6%, 2.7%;
      98.4%, 2.3%; 99.2%, 1.8%, respectively. CONCLUSION: The HPLC method is simple,
      sensitive and reliable, and can be used for the quality control of the medicinal
      material.

PMID- 19166011
TI  - [Fingerprint of Curcuma phaeocaulis by LC-MS].
AB  - OBJECTIVE: To study and establish the fingerprint of Curcuma phaeocaulis by high
      performance liquid chromatography-mass spectrometry. METHOD: LC-MS analysis was
      carried out in a Hewlett Packard model 1100 liquid chromatograph coupled with
      electrospray mass spectrometry. The analysis was performed on a ZORBAX RX-C18
      column (4.6 mm x 250 mm, 5 microm) with a mobile phase of methanol-isopropanol
      water (mathanoic acid 0.4%) in a gradient mode at a flow rate of 1.0 mL min(-1),
      and the column temperature of 35 degrees C. The wavelength of the UV detector was
      set at 254 nm. RSD values of precision, repeatability and stability of this LC-MS
      method were less than 5%. The total 10 batches of C. phaeocaulis from the
      different places of Sichuan province were detected, and different commodities and
      preparative methods were compared. RESULT: The standard fingerprint of the
      extract of C. phaeocaulis, which collected in the different places of Sichuan
      province, was originated from the Similarity Evaluation System for
      Chromatographic Fingerprint of TCM 2004' software, and 15 common peaks existed in
      the fingerprint. Each peak in the fingerprint was separated well under the above
      analysis condition and similarities of the extracts of C. phaeocaulis samples of
      the ten batches were all above 0.90. By comparison of the retention time and the
      on-line UV spectra and their molecular weights of the chemical standards, peaks 4
      6 and 9 were identified as curcumin (4), demethoxycurcumin (5), curcumenol (6),
      and curcumone (9), respectively. CONCLUSION: This LC-MS fingerprint and
      quantitative assessment can be used in the quality control of C. phaeocaulis.

PMID- 19166012
TI  - [Effects of exogenous epidermal growth factor (EGF) on growth inhibition induced
      by aristolochic acid I (AA-I) in renal proximal tubular epithelial cells].
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of exogenous
      epidermal growth factor (EGF) on the growth inhibition of renal proximal tubular
      epithelial cell induced by AA-I. METHOD: Cultured human renal proximal tubular
      epithelial cell line HK-2 was used as the subject. The changes of the survived HK
      2 cells were observed and compared among control, AA-I stimulation, pre-EGF,
      together-EGF and post-EGF groups. In the study, cellular morphologic assessments
      were performed with a phase-contrast inverted microscope. Cell counting after
      stained with 0.04% trypan blue was adopted to analyze cell proliferation. Cell
      cycle was assessed by flow cytometry. RESULT: Number of the survived cells
      stimulated by AA-I for 12, 24, 48 hours decreased gradually in a dose and time
      dependent manner. At 24, 48 hours, the survived cells showed a significant
      disturbance in the cell cycle procedure, which was characterized as decreased
      percentage of cells in G0/G1 phase, significant increased percentage of cells in
      G2/M phases. Exogenous EGF (20 microg L(-1)) could significantly promote the
      proliferation of HK-2 cells, which shown a increased cell number, accompanied
      down-regulated cells in G0/G1 phase, increased cells in S and G2/M phase.
      Compared with AA-I groups, it failed to improve the inhibitory effect on cell
      proliferation and abnormal cell cycle procedure by AA-I, no matter EGF was added
      in before, at same time or after AA-I stimulation. CONCLUSION: AA-I (10 g L(-1))
      has remarkable growth inhibition effects on survived RTEC, and can induce a
      blockage of G2/M phase in the cell cycle procedure. Exogenous EGF (20 microg L(
      1)) promote the proliferation in normal cultured HK-2 cell. EGF treatment could
      not improve the proliferation inhibitory effect induced by AA-I, no matter adding
      EGF to cultures before, together with AA-I or after AA-I stimulation.

PMID- 19166013
TI  - [Effects of Astragalus membranaceus on atrial dynamics and ANP secretion].
AB  - OBJECTIVE: To define the effects of Astragalus membranaceus on the atrial
      dynamics and ANP secretion in the perfused beating rabbit atria. METHOD: The
      experiments have been done in isolated perfused beating rabbit atria. ANP was
      measured by radioimmunoassay in the atrial perfusate in real-time base. RESULT:
      A. membranaceus (2.0, 2.5, 3.0 g L(-1)) could increase atria stroke volume from
      (694.70 +/- 0.01) microL g(-1) (P<0.05) to (1,003.00 +/- 8.80) microL g(-1)
      (P<0.001); (1,120.00 +/- 17.71) microL g(-1) and (1,195.00 +/- 8.21) microL g(-1)
      (P<0.001), respectively, and its could difference increase atrial pulse pressure
      from (0.82 +/- 0.01) kPa to (0.86 +/- 0.01) kPa (P<0.01); (0.96 +/- 0.01) kPa
      (P<0.001) and (1.02 +/- 0.01) kPa (P<0.001), respectively; A. membranaceus
      obviously increased rabbit atrial dynamics with dose-dependent manner.
      Simultaneously, A. membranaceus inhibited ANP secretion. Nifedipine (1.0 micromol
      L(-1)), a L-type Ca2+ channel inhibitor, and KB-R 7943 (10.0 micromol L(-1)), an
      inhibitor of reversed Na+ -Ca2+ exchanger, blocked the effects of A. membranaceus
      induced augmentation of atrial dynamics but failed to modulation the inhibition
      of A. membranaceus on ANP secretion. CONCLUSION: A. membranaceus increases the
      atrial dynamics via Na+ -Ca2+ exchanger and L-type Ca2+ channel and negatively
      modulates ANP secretion in beating rabbit atria.

PMID- 19166015
TI  - [Effect of matrine and oxymatrine on proliferation and expression of Stat3 and
      Stat5 in SMMC-7721 cell line].
AB  - OBJECTIVE: To study the effect of matrine and oxymatrine on proliferation and the
      expression of Stat3, Stat5 mRNA in SMMC-7721 cell line. METHOD: Treated with
      matrine and oxymatrine, the inhibitory effect on SMMC-7721 cell proliferation was
      detected by MTT, double fluorescence labeling was applied to measure the apotosis
      ratios of SMMC-7721cells, the expression of Stat3 and Stat5 mRNA in SMMC-7721
      cell line were assessed with RT-PCR. RESULT: Matrine and oxymatrine could inhibit
      the proliferation and induce the apoptosis of SMMC-7721 cells and it was time and
      dose dependent, the expression of Stat3 and Stat5 mRNA in SMMC-7721 cell with
      matrine and oxymatrine were significantly lower than those in control group
      (P<0.05 or P<0.01). Compared with the same dose of matrine and oxymatrine,
      matrine showed stronger effect on cell proliferation, apoptosis, and Stat3 and
      Stat5 mRNA (P<0.05 or P<0.01). CONCLUSION: Matrine and oxymatrine inhibited the
      proliferation and induced the of SMMC-7721 cells significantly, the mechanism of
      which might be related to the down-regulation of stat3 and stat5 mRNA and
      inhibition of the signaling transduction pathway.

PMID- 19166014
TI  - [Anti-cancer activity of Zuojinwan in vivo and influence to tumor markers in mice
      transplanted with sarcoma 180].
AB  - OBJECTIVE: To study the anticancer action of Zuojinwan in mice transplanted with
      sarcoma 180 in vivo, and detect the activities of five kinds of tumor markers
      (TM) including acid phosphotase (ACP), alkaline phosphotase (AKP), creatine
      kinase (CK), aldolase (ALD) and lactate dehydrogenase (LDH) in serum compared
      with Coptis chinensis and Evodia rutaecarpa. METHOD: The transplanted S180 tumor
      mice model was established, and the mice were divided randomly five groups. The
      extract of Zuojinwan (850.8 mg kg(-1)), C. chinensis (729.2 mg kg(-1)) and E.
      rutaecarpa (121.6 mg kg(-1)) were administrated, respectively for 10 d. Then, the
      changes of body weight, spleen index of mice, the inhibition rates of tumor, and
      the increase of life span (ILS) were all tested. In addition, the activities of
      ACP, AKP, CK, ALD and LDH on different test groups were also determined. RESULT:
      Zuojinwan could inhibit the S180 tumor growth significantly with the inhibition
      rate of 50.54% and the ILS of mice reached to 64.91%. Meanwhile, the activities
      of ACP (126.72 +/- 11.16) U 100 mL(-1) and AKP (67.27 +/- 13.49) U 100 mL(-1)
      were increased, and the activities of CK (20.65 +/- 4.28) U mL(-1), ALD (319.13
      +/- 53.87) U L(-1) and LDH (1,029.04 +/- 468.56) U L(-1) were decreased
      significantly by Zuojinwan treated group compared with C. chinensis and E.
      rutaecarpa treated groups (P<0.01). CONCLUSION: In the prescription of Zuojinwan,
      the enhancement of compatibility of anticancer activity was observed by the
      interaction of C. chinensis and E. rutaecarpa. The mechanism might be in
      according with to influence the activities of the five kinds of tumor markers
      (TM) in mice serum.

PMID- 19166016
TI  - [PTP1B inhibitory activities of bromophenol derivatives from algae].
AB  - OBJECTIVE: To study the protein tyrosine phosphatase-1B (PTP1B) inhibitory
      activity of natural products from algae aiming at searching for new way for the
      treatment of type 2 diabetes mellitus (T2DM) and obesity. METHOD: Bromophenols
      derivatives from algae were screened against the PTP1B by the colorimetric assay
      with GST/PTP1B fusion protein. The Me2SO was distributed as the full enzyme
      activity, and Na3VO4 (IC50 2 micromol L(-1)) was distributed as the positive
      control. Inhibition rate was assayed and IC50 were calculated by LOGIT method.
      RESULT: Three bromophenols from Rhodomela confervoides and Leathesia nana, 3, 4
      dibromo-5-(methoxymethyl)-1, 2-benzenediol (1), 2-methyl-3-(2, 3-dibromo4, 5
      dihydroxy)-propylaldehyde (2) and 3-(2, 3-dibromo-4, 5-dihydroxy-phenyl)-4-bromo
      5, 6-dihydroxy-1, 3-dihydroiso-benzofuran (3) showed significant inhibitory
      activity against PTP1B. IC50 values were 3.4 +/- micromol L(-1), 4.5 micromol L(
      1) and 2.8 micromol L(-1), respectively. CONCLUSION: The results prove that three
      bromophenol derivatives from algae with significant inhibitory activity against
      PTP1B were potential and effective therapeutic agents for treatment of T2DM and
      obesity.

PMID- 19166017
TI  - [Study of pharmacokinetics of aristolochic acid I and II in rats].
AB  - OBJECTIVE: To develop an HPLC method for determination of the plasma
      concentration of aristolochic acid I (AA I ) and aristolochic acid II (AA II) and
      study their pharmacokinetics in rats. METHOD: The plasma samples were extracted
      with acetonitrile. The analysis involved a C18 column as stationary phase and
      methanol, water and acetic acid as mobile phase. The flow rate was 1.0 mL min(
      1), the UV detection wavelength was 315 nm. After a single intravenous dose of 5
      mg kg(-1) AA in rats, the pharmacokinetic parameters were estimated. RESULT: The
      calibration curve of AA I was linear over the range from 0.056 mg L(-1) to 56.3
      mg L(-1) with a correlation coefficient of 0.9997. The mean recovery rate was
      88.7%. The RSD of within-day and between-day were all less than 8%. And the
      calibration curve of AA II was linear over the range from 0.192 mg L(-1) to 11.52
      mg L(-1) with a correlation coefficient of 0. 998 9. The mean recovery was 85.8%.
      The RSD of within-day was less than 3% and between-day was less than 10%. The
      main pharmacokinetic parameters were estimated to be as follows: CL = (0.010 +/-
      0.003) L min(-1) kg(-1), t(1/2alpha) = (8.2 +/- 1.7) min, t(1/2beta) = (79.6 +/-
      28.5) min for AA I; CL = (0.003 +/- 0.001) L min(-1) kg (-1), t(1/2alpha) = (56.7
      +/- 38.1) min, t(1/2beta) = (209.3 +/- 37.9) min for AA II. CONCLUSION: The
      established HPLC method is simple and sensitive to determine the concentration of
      AA I , AA II and the metabolite of AA I in rat plasma. From the result of
      animal's test, we can find that AA I was quickly eliminated from plasma, the
      elimination of AA II and Aristololactam-the metabolite of AA I - were slower than
      that of AA I.

PMID- 19166018
TI  - [Effect of puerarin on levels of TGF-beta1 and alpha-SMA in rats with alcoholic
      injury liver].
AB  - OBJECTIVE: To investigate the regulatory effects of puerarin on the levels of
      transforming growth beta1 (TGF-beta1) and alpha-smooth muscle actin (alpha-SMA)
      in rats with alcoholic injury liver, and to probe into the prevention and cure
      mechanism of puerarin on alcoholic liver injury. METHOD: Seventy five SD rats
      were randomly divided into 5 groups: normal group 10 rats. model group 20 rats
      (alcohol etc mixed liquor twice per day), control group 15 rats (alcohol etc
      mixed liquor + complex biejia ruangan pian 1 g kg(-1) d(-1)), puerarin high dose
      group 15 rats (alcohol etc mixed liquor + puerarin tablet 1.5 g kg(-1) d(-1)),
      puerarin low dose group 15 rats (alcohol etc mixed liquor + puerarin pill 0.75 g
      kg(-1) d(-1)). After 8 weeks. femoral vein blood of the rats were taken out in
      all rats and then rats were sacrificed to obtain liver samples. Samples were
      collected to observe pathological change and to detect expression of TGF-beta1,
      and alpha-SMA in liver tissue. RESULT: Pathological change and hepatic fibrosis
      integration of liver tissue in model group were significantly changed compared
      with other group (P<0.05). Meanwhile the level of TGF-beta1 and alpha-SMA in both
      high and low dose puerarin groups were significantly decreased compared with
      model group (P<0.01). Furthermore the level of alpha-SMA of puerarin high dose
      group were significantly decreased compared with control group (P<0.05), whereas
      there was no significant difference between puerarin low dose group and model
      group. CONCLUSION: There was an ascend in the level of TGF-beta1 and alpha-SMA
      expression in rats with alcoholic injury liver, and puerarin has regulatory
      effects on the expression of TGF-beta1 and alpha-SMA.

PMID- 19166019
TI  - [Anti-inflammatory and anti-allergic effects of acidic fraction of Pheratima
      extract in asthma mice induced by ovalbumin].
AB  - OBJECTIVE: To explore the effects of acidic fraction of Pheratima extract in an
      ovalbumin (OVA) induced asthma mouse model, and to provide the experimental
      evidences for the anti-asthmatic application of Pheratima extract with further
      purification and development. METHOD: Mice model of allergic asthma was
      established through the OVA challenge. To investigate the inflammatory cell level
      and Th1/Th2 levels as well as the therapeutic effects of acidic fraction from
      Pheratima extract, cell count of bronchoalveolar lavage fluid (BALF) was
      performed to evaluate the secretion of eosinophils (EOS) cells, and IgE, IL-4, IL
      5, IL-13, IFN-y levels were detected by ELISA. RESULT: Compared with control
      group, the EOS count of BALF in the model group was remarkably increased
      (P<0.01), and IgE, IL-4, IL-5, IL-13 levels were also increased (P<0.01), while
      IFN-gamma decreased (P<0.01). Acidic fraction from Pheratima (S) extract and its
      30% ethanol washed fraction (S30) significantly inhibited the increase of EOS
      count (P<0.01), decreased the IgE, IL-4, IL-5, IL-13 levels (P<0.05), and
      inhibited the decrease of IFN-gamma level (P<0.01). CONCLUSION: The results
      indicate that inhibition of the EOS secretion and balancing of the altered
      Th1/Th2 levels may be important mechanisms of Pheratima's therapeutic effect in
      asthmatic mice model, and S30 is pharmacologically effective as evaluated with
      the above mentioned parameters, as a representative fraction of the Pheratima
      extract.

PMID- 19166020
TI  - [Retrospective analysis on Chinese medicinal treatment on 302 chronic heart
      failure patients of coronary heart disease and diabetes].
AB  - OBJECTIVE: To explore the characteristics of Chinese medicinal treatment on 302
      chronic heart failure (CHF) patients of coronary heart disease and diabetes.
      METHOD: Data of CHF patients of coronary heart disease and diabetes hospitalized
      in 9 hospitals of Beijing and Tianjin from Jan. 2003 to Sep. 2006 were collected
      and their clinical syndromes, condition of treatment (both western and Chinese
      medicine) were investigated and analyzed using the data system of Chinese
      medicine clinical research for coronary heart disease. RESULT: In the 302
      patients, the intravenous perfusion were mainly injections of puerarin, Salvia
      mitrorrhiza, sanchi total saponin and fleabane. The Chinese medicinal treatment
      applied was mainly the methods of supplementing Qi, activating blood circulation,
      dissolving phlegm. In the apozem, hoelen is the highest frequency in all drugs
      and the frequency in order is hoelen, glycyrrhizae, Salvia mitrorrhiza,
      astragali, Rhizoma Pinelliae, etc. CONCLUSION: The patients of these 9 hospitals
      were mainly treated by integrative medicine and the Chinese medicinal treatment
      applied was mainly the methods of supplementing Qi, activating blood circulation,
      dissolving phlegm.

PMID- 19166021
TI  - [Studies and reports of Chinese cut crude drug's dosage in clinical prescription
      of (section of medical department)].
AB  - OBJECTIVE: Study the actual dosage of clinical prescription in medical department
      of traditional Chinese medicine (TCM), and offer the consummate data for
      formulating the dosage standard of Chinese cut crude drug. METHOD: We made use of
      the methods of stratified sampling and random sampling to investigate 269 882
      broth prescriptions of Medical Department of TCM in 21 various hospitals, 18
      provinces, and constructed the database, then applied Weka KDD software to
      analyze. RESULT: We identified the frequency and clinical dosage intervals of 300
      drugs, and the practical dosage of 155 drugs which dose has difference between in
      the actuality and in the pharmacopoeia. Most of drug's dosage centralized the
      four intervals: (3-6], (9-12], (12-15], (18-21], and the concrete dosage were 3,
      6, 10, 12, 15, 20 g, etc. CONCLUSION: The dosages in the pharmacopoeia are not
      coincided with the practical dosages in internal medicine, and demand to revise.
      This paper will offer the consummate data for formulating the new dosage
      standard.

PMID- 19166022
TI  - [Study on measuring units of Chinese medicine in Song dynasties].
AB  - The original changes of the weight measuring unit of medicine in the Song
      dynasties was the appearance of Dengzi (small steelyard for weighing money). The
      "larger scale" and "smaller scale" were unified. The measuring unit "qian" was
      widely used, and furthermore "Cheng" and "zi" were used as measuring units
      related to medicine.

PMID- 19166023
TI  - [Discussion on optimizing data processing of Chinese materia medica].
AB  - Correct data without noise is the basis for obtaining useful information and
      knowledge. The database system of Chinese materia medica is the application of
      database technology in the field of Chinese materia medica. Its establishment is
      based on the analysis, processing and supplementary of much irregular raw data
      during studying Chinese materia medica information. This paper reviewed several
      key problems in the data processing of Chinese materia medica based on the
      information system of Chinese herbal medicine that we are constructing.

PMID- 19166024
TI  - [Discussion about cervical incision of goiter in mediastinum posterior and its
      indications].
AB  - OBJECTIVE: To explore the feasibility of cervical approach for goiter in
      posterior mediastinum. METHOD: According to the mechanism that goiter filed into
      posterior mediastinum and the dissection of thyroid gland and mediastinum, we
      designed the following surgery principles (1) From top to bottom. (2) Find out
      recurrent nerve at the place where it enters larynx, then dissect recurrent nerve
      as long as possible and protect it carefully, meanwhile, search thyroid vessels
      along recurrent nerve. (3) To avoid and uncontrollable serious hemorrhage in the
      operation, all normal and aberrant blood vessels must be ligated cautiously, and
      avoid pulling great vessels in the thoracic part. (4) Separating tumor of
      hemorrhage under surgical capsule. Bluntly, it can avoid damage important
      structure in most occasions. (5) If the tumor of hemorrhage was difficult to be
      separated from the surrounding structure, ask thoracic surgeon for cooperation.
      RESULT: Two operations case were operated under the above guideline successfully,
      and the operations were performed with satisfactory effect, minimal invasion,
      rapid recovery and low medical cost. CONCLUSION: Cervical approach for goiter in
      mediastinum posterior is an ideal method of surgery, but it has following
      operative indication. (1) imaging date indicate that tumor of posterior septum is
      not connected to the surrounding structure. (2) It is not accompanied with
      superior vena cava syndrome. (3) The size of large thyroid tumor of posterior
      septum could be decreased by taking out the center part of tumor, and it is
      suitable for liquidized center tissue especially, then take out the tumor from
      neck. If it is hard to be taken out, you can ask thoracic surgeon for help.

PMID- 19166025
TI  - [Application of SELDI-TOF-MS technology in study of laryngeal carcinoma
      biomarkers].
AB  - OBJECTIVE: In order to establish a primary diagnosis model of laryngeal
      carcinoma, we explore the changes of proteomic spectra in serum from patients
      with laryngeal carcinoma and healthy controls. METHOD: Proteomic spectra of 32
      serum samples from laryngeal carcinoma (18 cases of glottis and 14 of
      supraglottis) patients and 38 from healthy people whose age and sex was matched
      were generated by IMAC3-Cu protein chip array and SELDI-TOF-MS (surface was
      enhanced laser desorption/ionization time-of-flight mass spectrometry). The
      discriminatory profiling between cancer and normal samples was analyzed by
      Biomarker Wizard software and Biomarker Pattern software. RESULT: Fifteen
      differentially expressed proteins in serum were screened by analysis of proteomic
      spectra of preoperative patients and normal subjects. Eight proteins (3795.04,
      5068.18, 5339.78, 5908.28, 6629.74, 9266.32, 13879.6 and 14037.1) were obtained
      for making up patterns that was able to class the patients team and normal team
      correctly. Corresponding correct ratio were 87.50% (28/32) and 86. 84% (33/38).
      CONCLUSION: SEI.DI-TOF-MS Protein Chip technology is a new tool for the early
      diagnosis of laryngeal carcinoma.

PMID- 19166026
TI  - [Effect of CDK2 on proliferation in laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the role of CDK2 in the development of DNA heteroploid
      in laryngeal squamous cell carcinoma (LSCC). METHOD: Fifty specimens of LSCC,
      twelve specimens of atypical hyperplasia and thirty specimens of vocal cord polyp
      were obtain during operation. Centrosome were detected by anti tubulin
      antibodies. Immunohistochemical method was used to analyze the protein expression
      of CDK2 and gamma-tubulin. RESULT: The positive rate of CDK2 and gamma-tubulin in
      LSCC were 68.0% (34/50) and 78.0% (10/15), all of them were significant higher
      than those in the vocal cord polyp (P<0.05). Expression of CDK2 in LSCC was
      positively association with expression of gamma-tubulin. CONCLUSION: This
      experiment indicated that overexpression of CDK2 was strongly correlated with
      abnormal proliferation in LSCC, and it may be a valuable marker for the diagnosis
      and therapy of LSCC.

PMID- 19166027
TI  - [Analysis of management on 23 cases of carotid body tumors].
AB  - OBJECTIVE: By reviewing the clinical material in 23 cases (25 tumors) of carotid
      body tumors, we concluded our experience in selecting the appropriate diagnostic
      modality and surgical therapy to facilitate surgical maneuvers and decrease the
      incidence of postoperative complications. METHOD: From 2003 to 2008, 23 cases of
      carotid body tumors were admitted and treated in Wuhan Union Hospital. All the 23
      cases were operated after determining diagnosis that was deterred by angiography
      and noninvasive examinations including color Doppler scan, computed tomography
      angiography and magnetic resonance angiography. RESULT: There was no patient
      died, no cerebral infarctions, no recurrence after operation. Nervous
      complications occurred in 5 cases post operatively. CONCLUSION: Preoperative
      angiography is a appropriate diagnostic modality for carotid body tumor, which
      can shows the supply arteries of the tumor and estimate the structure of the
      Willis Circle, so that we can judge the possibility to temporarily clamp the
      carotid artery during the operation to control the hemorrhage and eliminate the
      postoperative nervous complications.

PMID- 19166028
TI  - [A simple method of separating outer hair cells in Guinea pig].
AB  - OBJECTIVE: In order to meet the needs of electrophysiology outer hair cells, we
      investigate a method to separate outer hair cells simply and effectively. METHOD:
      The basal membrane was dissected combined with spiral ligament and axis of
      cochlea, then incubated with enzyme, and then mechanically triturated by
      micropipette. RESULT: A large number of living outer hair cells were obtained. Of
      80% cells could keep good condition in 6 hours. CONCLUSION: If increasing the
      enzyme concentration slightly and the large part of cochlea without outer bone
      was enzymes, we can get living outer hair cells easily.

PMID- 19166029
TI  - [The clinical analysis of cat scratch diseases with enlarged masses].
AB  - OBJECTIVE: In order to raise awareness of CSD and reduce misdiagnosis, we study
      the manisfection and treatment of CSD with enlarged masses. METHOD: A
      retrospective study was carried out among the 10 identified patients with CSD on
      the basis of compatible clinical presentation and confirmatory pathology results
      for CSD. RESULT: All the 10 patient's first symptoms were masses at some part of
      the body, more common in the neck. The ratio was 5% at neck, 3% at armpit, 1% at
      upper, 1% at groin. Two patients had low heat, increased leukocyte and larger
      masses of more than 2 cm in diameter After surgical resection, and anti
      inflammatory treatment. All the patients were cured after surgery and
      postoperative anti-inflammatory treatment, and there was no recurrence during the
      7-year follow-up. CONCLUSION: If patients were diagnosed and treated timely, the
      prognosis will be good. For the cases with extremely enlarged lymphonodus,
      surgical operation followed by antimicrobial chemotherapy will be a effective
      treatment.

PMID- 19166030
TI  - [Diagnosis and treatment of serious adult airway obstruction].
AB  - OBJECTIVE: To investigate the diagnosis and treatment of serious adult airway
      obstruction. METHOD: Eighty six adult cases admitted to our hospital for serious
      airway obstruction from 1995 to 2006, were analyzed retrospectively. RESULT:
      Among the 86 cases, 34 cases (39.5%) had inflammatory diseases, 32 cases (37.2%)
      had neoplastic diseases and 9 cases (10.5%) had traumatic diseases. In addition,
      3 cases of laryngeal spasm, 6 cases of laryngeal stricture, 2 cases of bilateral
      laryngeal paralysis and 1 case of asphyxia with aspiration were also include in
      this study. The patients who had laryngeal or tracheal obstruction were 60 cases
      (69.8%) and 13 cases (15.1%). In addition, 46 cases (53.5%) and 4 cases (4.7%)
      had tracheotomy or endotracheal intubation. Twenty six cases were only adopted
      medical treatment to relieve dyspnea. The final diagnosis of the 86 cases was
      made and the serious airway obstruction was was relieved within 2 hours. While 14
      cases (16.3%) had serious complications and 6 cases (6.9%) had operative
      complications occurred. One cases (0.2%) died. CONCLUSION: The causes of serious
      adult airway obstruction could be complicated, the site and character of
      obstruction would change constantly. Quick diagnosis, timely removal of the
      obstruction should be critical factors to improve curative effect.

PMID- 19166031
TI  - [Study of the lymph node micrometastasis in patients with supraglottic
      carcinoma].
AB  - OBJECTIVE: To explore an available and sensitive method to detect cervical lymph
      node micrometastasis in patients with laryngeal squamous cell carcinoma. METHOD:
      The primary tumors and 182 neck lymph nodes from Twenty cases with supraglottic
      cancer dissection were examined with immunohistochemical (IHC) staining using
      cytokeratin 19 (CK19), and haematoxylin and eosin (HgE) staining. The frequency
      of lymph node metastasis and the clinical relevance, and the relationship between
      overall survival time and lymph node metastases by Log Rank test were analyzed.
      RESULT: The expression of CK19 was 23. 6% of lymph nodes and all of the primary
      tumors. In Hg-E staining, 16.5% of lymph nodes were positive. There was highly
      significant difference between them. There were 88.4% lymph nodes, 9.3% lymph
      nodes and 2.3% lymph node corresponding to the II, III and IV levels by IHC.
      Lymph node metastases were detected on the II (86.7%) and III levels (13.3%) with
      H&E. The highest rate of positive lymph nodes was on the II level of the neck.
      There was highly significant difference between overall survival time and lymph
      node metastasis in CK19 analysis. CONCLUSION: The expression of CK19 may be
      served as an available method to evaluate occult micrometastases in laryngeal
      squamous cell carcinoma. High frequency of CK19 was associated with a decreased
      probability of survival time.

PMID- 19166032
TI  - [Extended supracricoid partial laryngectomy with tracheocricohyoidoepiglottopexy
      and tracheocricohyoidoglottopexy].
AB  - OBJECTIVE: To investigate the surgical procedure and indication of the Extended
      supracricoid partial laryngectomy with tracheocricohyoidoepiglottopexy and
      tracheocricohyoidoglottopexy (ESCPL+-TCHEP/TCHP) as well as the rehabilitation of
      laryngeal functions. METHOD: ESCPL+TCHEP/TCHP were conducted in 10 cases with
      laryngeal carcinoma of T3 and T4 stages with subglottic invasion for 10-20 mm
      from 2000 to 2005. RESULT: All the 10 cases, 9 of them have survived until now
      and still be followed up. 1 of them succumbed to the recurrence of cervical lymph
      node metastasis 4 years after the surgery. Normal respiration, deglutition and
      the function of maintaining subglottic pressure were recovered in all the case.
      Postoperative phonation was also satisfactory among all of them. CONCLUSION: If
      handle the surgical indication strictly, to some cases of laryngeal carcinoma
      with subglottic invasion for 10-20 mm, this surgical technique could replace the
      total laryngectomy.

PMID- 19166033
TI  - [Expression and its significance of aquaporin 5 in nasal polyps with or without
      allergic rhinitis].
AB  - OBJECTIVE: To confirm the expression and distribution of aquaporin 5 (AQP5) in
      nasal polyps. METHOD: AQP5 were studied in 20 samples nasal polyp without AR
      (Group NAR) and 16 samples with AR (Group AR) with immunochemistric staging and
      its integrated light intensity and its grey step. RESULT: (1) Hematoxylin and
      eosin staining showed that there was obvious inflammation reaction, a large
      quantity of glands hyperplasia and acidophils soaked in nasal polyps, especially
      those with allergic rhinitis. (2) Immunofluorescence technique showed that the
      distribution of AQP5 in the two groups was in accordance with that in nasal
      polyps on the whole. AQP5 expressed mainly in the membrane and cytoplasm of the
      epithelium of the glands, ducts and cilia. (3) The statistical analysis of the
      immunohistochemical staining showed that the integrated light intensity of AQP5
      in Group AR (0.1675+/-0.006536) was obviously higher than that in the Group NARs
      nasal polyps (0.09343+/-0.001816). There was statistical significance between the
      two groups (t = -12.00, P<0.01). (4) The statistical analysis of the
      immunohistochemical staining showed that the grey step of AQP5 in Group AR
      (175.6+/-2.471) was obviously lower than that in the Group NAR's nasal polyps
      (206.2+/-0.9649). There was statistical significance between the two groups
      (t=12.46, P<0.01). CONCLUSION: AQP5 is expressed in nasal polyp. Combined with
      the research before, it was conferred that the hypersecretion of glands and its
      character has a relationship with the high expression of AQP5 in nasal polyps,
      and nasal polyp with different symptom has different mechanism.

PMID- 19166034
TI  - [Construction siRNA expressing vector of Skp2 and the inhibitory effects on the
      expression of Skp2 in laryngeal carcinoma cell line Hep2 cell].
AB  - OBJECTIVE: To construct the siRNA expression vector of Skp2 and inhibit the
      expression of Skp2 through RNA interference in laryngeal carcinoma cell line Hep2
      cell. METHOD: According to the encoding sequence of mRNA of Skp2, two pieces of
      oligonucleotide sequences were designed and synthesized. The annealed
      oligonucleotide fragments were subcloned into pGPU6/Neo siRNA expression vector,
      and the recombinant plasmid was transformed into strain DH5a. The plasmid
      identified by restriction enzyme was used for sequencing. After being identified
      by sequencing, the recombinant plasmids pGPU6Skp2 were transfected into Hep2
      cells. Skp2 expression in the transfected cells was assayed by flow cytometry.
      RESULT: DNA sequencing showed that the oligonucleotide fragments were correctly
      inserted into pGPU6 vector, and Skp2 expression in the transfected cells was down
      regulated significantly by pGPU6Skp2 at the protein level. CONCLUSION: The siRNA
      expression vector of Skp2 was successfully constructed and could inhibit Skp2
      expression in Hep2 cells. This result will facilitate further studies of Skp2 in
      gene therapy for tumors.

PMID- 19166035
TI  - Recent technical and engineering advances in magnetic resonance imaging (MRI) and
      ultrasound.

PMID- 19166036
TI  - Correlative anatomy of the anus and rectum.
AB  - An overview of the normal anatomy of the anus and rectum is provided with an
      emphasis on correlative imaging, including computed tomography, magnetic
      resonance, and ultrasound. The major clinically important structures that can be
      assessed with these imaging modalities are reviewed.

PMID- 19166037
TI  - Magnetic resonance imaging in fecal incontinence.
AB  - Fecal incontinence is a frequent condition. The workup of patients with fecal
      incontinence comprises clinical history, physical examination, anofunctional
      tests and imaging. In many institutions, imaging in these patients concerns
      endosonography. Magnetic resonance imaging (MRI) is a valuable alternative to
      endosonography. For detection of external sphincter defects the techniques have
      comparable results. However, visualization of the external sphincter at MRI is
      superior to endosonography, facilitating identification of external sphincter
      atrophy. External sphincter atrophy at MRI is related to poor outcome of anterior
      anal repair and therefore MRI should be considered in potential candidates for
      anterior anal repair. External coil MRI is a widely available alternative to
      endoanal MRI and can be used as an alternative in experienced hands.

PMID- 19166038
TI  - Magnetic resonance defecography: an evaluation of obstructed defecation and
      pelvic floor weakness.
AB  - Magnetic resonance defecography is an effective method of evaluating pelvic floor
      weakness and anorectal dysfunction. With no ionizing radiation, less than 30
      minutes of imaging, and complete anatomic and functional detail, magnetic
      resonance has largely supplanted other imaging modalities. This contribution
      reviews the pertinent pelvic anatomy, image acquisition, and image interpretation
      and briefly discusses the most common pathology.

PMID- 19166039
TI  - Practical performance of defecography for the evaluation of constipation and
      incontinence.
AB  - By opacifying the sigmoid, rectum, and vagina with different barium consistencies
      and using fluoroscopy to evaluate the mechanics of defecation in a physiologic
      setting, a wide range of pathologies associated with constipation and
      incontinence can be diagnosed. This review article discusses the primary
      indications for fluoroscopic defecography, techniques, common diagnoses, and
      challenges faced in clinical practice.

PMID- 19166040
TI  - Ultrasound staging of rectal cancer.
AB  - Endorectal ultrasound (ERUS) is a primary imaging technique in the preoperative
      evaluation of patients with rectal adenocarcinoma. The purpose of this report is
      to review ultrasound staging with emphasis on technique and potential pitfalls.
      The role of ultrasound in multimodality staging and surveillance is also
      explored. An awareness of inherent imaging challenges and implications may
      optimize staging accuracy and resultant management of rectal cancer patients.

PMID- 19166041
TI  - Magnetic resonance imaging in locoregional staging of rectal adenocarcinoma.
AB  - A comprehensive overview of the current status of magnetic resonance imaging
      (MRI) in the locoregional assessment and management of rectal adenocarcinoma is
      presented. Staging systems for rectal cancer and treatment strategies in its
      management are discussed to give the reader the context that shapes MRI
      acquisition techniques and interpretation. Findings on MRI are detailed and their
      accuracy reviewed based on currently available evidence. Optimization of MRI
      acquisition and relevant pelvic anatomy are reviewed. A detailed description of
      our approach in interpreting MRI for locoregional staging of rectal cancer is
      given and future directions are also introduced.

PMID- 19166042
TI  - Current techniques in imaging of fistula in ano: three-dimensional endoanal
      ultrasound and magnetic resonance imaging.
AB  - Perianal fistula is an abnormal communication between the anal canal and perianal
      skin. The majority of perianal fistulous disease results from either
      cryptoglandular inflammation or Crohn's disease. These groups differ in
      pathophysiology, prognosis, and strategies for imaging and treatment. Endoanal
      ultrasound and magnetic resonance imaging represent current imaging strategies
      for evaluating perianal fistulas and may be used alone or in combination. The use
      of three-dimensional technique and peroxide fistulography optimize the ultrasound
      evaluation of perianal fistula. The use of multiple imaging planes and sequences
      including fat suppression and contrast enhancement optimize the magnetic
      resonance imaging protocol. Examples of the imaging appearance of perianal
      fistulas and a proposed flowchart for imaging modality selection are provided.

PMID- 19166043
TI  - Anorectal trauma: the use of computed tomography scan in diagnosis.
AB  - Anorectal injuries represent a relatively uncommon but clinically critical
      diagnosis in trauma. Anorectal injuries may be the result of penetrating injuries
      to the pelvis and perineal area as well as severe blunt traumatic injuries, often
      with pelvic fractures. The purpose of this review is to discuss injuries to the
      anorectal region sustained in trauma, specifically, in the application of
      multidetector computed tomography technology to these imaging diagnoses. An
      understanding of the pertinent anatomy is critical in characterization of these
      injuries using computed tomography (CT). Additionally, the subsequent clinical
      management decisions and how they are impacted by severity and location of injury
      in anorectal trauma is useful to the radiologist. This should serve to highlight
      the specific areas and injury distinctions that deserve our particular attention
      given possible changes in the ensuing management approaches. CT protocol issues
      including the use of oral, rectal, and intravenous contrast, as necessary, are
      relevant in maximizing the diagnostic accuracies of CT in anorectal trauma. This
      review serves to discuss and illustrate these pertinent issues, approaching
      penetrating and blunt trauma separately, with the emphasis on multidetector
      computed tomography in diagnosis.

PMID- 19166044
TI  - Transanorectal interventions.
AB  - Over the past few decades, advances in modern imaging technology have enabled
      less invasive approaches to diagnose and treat disease. In the field of image
      guided techniques, this has seen the common adaptation of needle biopsy and
      catheter drainage into clinical practice. In this article we review the most
      common applications of transanorectal techniques. As nearly all these techniques
      are performed under ultrasound guidance in dayto-day practice, the review focuses
      almost exclusively on ultrasound-enabled techniques.

PMID- 19166045
TI  - Backyard chicken flocks pose a disease risk for neotropic birds in Costa Rica.
AB  - Pathogens of free-ranging chickens create a risk of disease for wild birds, some
      of which migrate to the United States, as well as potential economic losses for
      resource-poor farmers. Free-roaming backyard chickens are commonly kept in shade
      grown coffee plantations, habitats that attract large numbers of wild birds. The
      husbandry and pathogen prevalence of backyard chicken flocks in San Luis, Costa
      Rica, were investigated. Based on serologic evidence, Newcastle disease virus,
      infectious laryngotracheitis virus, infectious bronchitis virus, chicken anemia
      virus, and infectious bursal disease virus, as well as both Mycoplasma
      gallisepticum and Mycoplasma synoviae, appear to be significant diseases of this
      population, and thus, we consider these backyard chickens potential reservoirs
      for these diseases. There was no evidence of avian influenza. Interviews,
      clinical examinations, and microscopic examination of tissues led us to believe
      that poxvirus is also a significant cause of morbidity and mortality in these
      chickens. We found that Escherichia coli isolates were resistant against
      tilmicosin, tetracycline, ampicillin, amoxicillin with clavulanic acid,
      ticarcillin, and cephalothin, and contained genes considered responsible for
      conferring tetracycline resistance. Additionally, although production was not
      measured, we suspect that husbandry and lack of preventative medicine are
      directly related to the diseases reported, all of which negatively affect
      production.

PMID- 19166046
TI  - Passive immunity of progeny from broiler breeders vaccinated with oil-emulsion
      bacterin against Salmonella enteritidis.
AB  - Young poultry are very susceptible to Salmonella Enteritidis (SE) infections
      because of the absence of complete intestinal flora colonization and an immature
      immune system. This study evaluated the role of passive immunity on the
      resistance of young birds against early infections caused by SE. The progeny of
      broiler breeders vaccinated with an oil-emulsion bacterin was compared to the
      progeny of unvaccinated birds. Efficacy was determined by challenging birds at 1
      and 14 days of age with SE Nal Spc strain, phage type 4. After challenge at 1 day
      of age, the progeny of vaccinated birds presented a significantly lower number
      (log10) of SE Nal Spc reisolation (P < 0.05) in liver (2.21), spleen (2.31), and
      cecal contents (2.85) compared with control groups (2.76, 3.02, and 6.03,
      respectively). The examination of the internal organs, 3 days after infection,
      revealed that 28% of the birds (7/25) from vaccinated breeders were positive,
      whereas 100% (25/25) of the chicks derived from unvaccinated birds were positive.
      Birds challenged at 14 days of age presented a lower number of positive samples
      compared with those challenged at 1 day of age, and the progeny of vaccinated
      birds presented statistically lower numbers (log10) of colony-forming units/ml of
      SE Nal Spc only in the cecal contents compared with nonvaccinated breeder progeny
      (2.11 vs. 2.94). Age seems to influence the susceptibility of birds to SE
      infections: in control groups, the number of positive birds at 14 days of age
      (9/25) was lower when compared with the group infected at 1 day of age (25/25).
      The number of positive fecal samples of the progeny of vaccinated birds was
      significantly lower (36) than those of the control group (108) after challenge at
      1 day of age. Unchallenged progeny of vaccinated birds presented passive
      antibodies detectable by enzyme-linked immunosorbent assay (ELISA) up to 21 days
      of age. On the other hand, antibodies of the control group were detected by ELISA
      14 days after challenge. These results show a significant contribution of breeder
      vaccination by increasing the resistance of the progeny against early SE
      infections. However, the bacteria were not completely eliminated, suggesting that
      additional procedures are needed to effectively control SE infections.

PMID- 19166047
TI  - Marek's disease virus infection in the eye: chronological study of the lesions,
      virus replication, and vaccine-induced protection.
AB  - Marek's disease virus (MDV) infection in the eye was studied chronologically
      after inoculating 1-day-old chickens with a very virulent MDV strain, Md5. The
      ocular lesions could be classified as early lesions (6-11 days postinoculation
      [dpi]) and late lesions (26 and 56 dpi), based upon the location and severity of
      the lesions. The early lesions involved iris, ciliary body, and choroid layer,
      and were characterized by endothelial cell hypertrophy, vasculitis, and
      infiltration of lymphocytes (mainly CD8+), plasma cells, macrophages, and
      heterophils. Expression of early MDV-antigen pp38 in the cells infiltrating
      choroid layer was detected as early as 11 dpi. Late lesions consisted of severe
      lymphohistiocytic uveitis, keratitis, pectenitis, vitreitis, retinitis, and
      segmental to diffuse retinal necrosis. Cell infiltration included macrophages,
      granulocytes, plasma cells, and both CD4+ and CD8+ cells of various sizes.
      Expression of early MDV-antigen pp38 was readily found within the retina, uveal
      tract, and corneal epithelium. No expression of late-antigen gB or oncoprotein
      meq was detected in any of the eyes examined. A second experiment was conducted
      to study the effect of vaccination on the development of ocular lesions. Both HVT
      and CVI988 were able to protect against the development of early ocular lesions
      in chickens infected with very virulent plus strain MDV 648A. However, only
      CVI988 conferred complete protection against the development of late ocular
      lesions. HVT conferred partial protection, as it reduced the frequency and
      severity of the late ocular lesions. These results enhance our understanding of
      the nature and pattern of MDV infection in the eye.

PMID- 19166048
TI  - The effects of stress on respiratory disease and transient colonization of
      turkeys with Listeria monocytogenes Scott A.
AB  - Listeria monocytogenes contaminates poultry processing plants due to its
      ubiquitous nature and high resistance to disinfection. The sources of the
      persistent, biofilm-forming strains that colonize processing plants are unknown.
      The purpose of this study is to determine if intrinsic colonization of turkeys is
      a possible source of contamination. Male poults were subjected to cold stress
      from 4-12 days of age; poults were unchallenged or were exposed to an aerosol and
      oral challenge of either an avian pathogenic strain of Escherichia coli (Ec), the
      Scott A strain of L. monocytogenes (Lm), or to a combination (Ec-Lm). At 7 wk,
      all cold-stressed poults were treated with an immunosuppressive dose of
      dexamethasone (Dex) and exposed to the same bacterial challenges. Birds were
      necropsied at 1 wk and 2 wk post-Dex treatment. Percent mortality, body and organ
      weights, and airsacculitis scores were determined. Liver and knee synovial
      tissues were sampled, using transport swabs, and cultured by direct plating, pre
      enrichment, and Taqman real-time PCR. There were no significant differences in
      cumulative mortality, and airsacculitis scores were variable but tended to be
      decreased by cold stress. Relative weights of liver and heart were increased,
      whereas body weights, and spleen and bursa relative weights, were decreased
      following all challenges. Listeria monocytogenes was isolated from up to 50% of
      liver or knee synovial tissues, using pre-enrichment followed by culturing
      methods, and from up to 67% of knee synovial tissues using pre-enrichment
      followed by real-time PCR at 1 wk post-challenge. The higher percentages of
      positive birds, detected by real-time PCR rather than by culture, and the
      negative results at 2 wk post-challenge suggest that the birds experienced a
      transient infection that was cleared by the immune system. These results suggest
      that environmentally acquired L. monocytogenes can transiently colonize the liver
      and synovial tissues of stressed turkeys and may be a sporadic source of
      contamination of processing plants.

PMID- 19166049
TI  - Detection of infectious bursal disease virus isolates with unknown antigenic
      properties by reverse genetics.
AB  - Infectious bursal disease virus (IBDV) serotype 1 is the causative agent of a
      highly contagious immunosuppressive disease of young chickens. In the past, a
      number of antigenic, as well as pathogenic, subtypes have been described. The
      determination of the antigenic makeup of circulating strains is of vital interest
      to the poultry industry because changes in the antigenicity of circulating field
      strains have an impact on the use of vaccines. To obtain a more comprehensive
      overview of the relationship between the nucleotide and amino acid sequence and
      the antigenic makeup of field isolates, a system based on reverse genetics of
      IBDV was established. Using this approach, a database for field isolates from
      three different states in the United States (Georgia, Alabama, and Louisiana),
      consisting of nucleotide sequence, amino acid sequence, and a reaction pattern
      based on a panel of monoclonal antibodies, was established. The obtained results
      showed that phylogenic analysis, which is based on the similarity of sequences,
      would lead to false conclusions regarding a possible antigenic makeup of the
      particular isolate. Sequences of field samples were divided into three groups: 1)
      those that grouped with variant strain E/Del sequences but were antigenically
      different, 2) those that did not group with sequences of E/Del but were similar
      in their antigenic makeup, and 3) those that did not group with E/Del sequences
      and were antigenically different. In addition, using the reverse-genetics
      approach, a number of field isolates showed no reactivity with any of the used
      monoclonal antibodies, indicating that an unknown, antigenic subtype of IBDV
      serotype 1 is circulating in the field.

PMID- 19166050
TI  - Using bacteriophages to modulate Salmonella colonization of the chicken's
      gastrointestinal tract: lessons learned from in silico and in vivo modeling.
AB  - An increasing prevalence of antibiotic-resistant foodborne infections has
      resulted in considerable concern about how antimicrobials are used in meat and
      poultry production. Because many foodborne bacterial pathogens are commonly found
      among the intestinal bacterial community of poultry, new methods of prevention
      are being considered. Bacteriophage therapy is one such alternative method that
      has not been well developed in the United States; however, bacteriophages have
      been shown to be effective in modulating bacterial numbers in acute infection
      models. In this study we evaluated whether bacteriophages could theoretically
      reduce Salmonella colonization of the gastrointestinal tract of chickens. Using
      computer simulations, we studied bacteriophage and bacterial replication dynamics
      in a mathematical model based on parameters expected to occur in the intestinal
      environment. In addition, we performed in vivo experiments by administering SP6
      bacteriophage and Salmonella orally to young chickens and compared the levels of
      phage and Salmonella shed in the feces to the models of replication dynamics. SP6
      is an ideal candidate bacteriophage because its genome and target receptor are
      known. Although SP6 did not reduce the levels of Salmonella shed by treated
      birds, most of the isolates recovered from treated birds were not resistant to
      the bacteriophage. These results suggest that phage resistance may not be the
      primary limiting parameter of phage prophylaxis for modulating colonization of
      the intestine. Our findings that this phage could be replicated in vivo supports
      the attractiveness of phage use, because unlike antibiotics they may be amplified
      in vivo if given a suitable host on which to replicate. If successful, this
      approach to modulating bacterial colonization of the intestinal tract could have
      a tremendous effect on the meat and poultry industry by reducing the use of
      antimicrobial drugs and increasing the use of biological therapeutics.

PMID- 19166051
TI  - Infectious bronchitis virus in the chicken Harderian gland and lachrymal fluid:
      viral load, infectivity, immune cell responses, and effects of viral
      immunodeficiency.
AB  - We compared detection of infectious bronchitis virus (IBV) by quantitative RT-PCR
      (qRT-PCR) in tears and trachea of IBV-infected chickens and found that
      quantitative detection of IBV RNA in tears is more sensitive than in tracheal
      homogenates. Furthermore, we demonstrated that IBV contained in chicken lachrymal
      fluid is infectious and that tears of IBV-infected chickens can be used to infect
      naive chickens. We compared the immune responses to IBV in the Harderian gland
      and cecal tonsils of immunocompetent chickens and chickens infected with chicken
      anemia virus (CAV) and/or infectious bursal disease virus (IBDV). Flow cytometry
      analyses of lymphocytes in Harderian glands and cecal tonsils indicated that the
      relative abundance of IgM+ B cells in the Harderian glands and cecal tonsils
      following exposure to IBV in combination with immunosuppressive viruses was
      reduced compared to chickens infected with IBV alone. CAV, but not IBDV, reduced
      the CD4+/CD8+ T cell ratios compared to chickens infected with IBV alone. Enzyme
      linked immuno-spot forming assays on cells in the Harderian glands and cecal
      tonsils of IBV-infected chickens indicated that maximum IBV-specific IgA
      secreting cell responses were reduced in chickens infected with CAV. IBDV co
      infected chickens displayed a delayed IgA response to IBV. Thus immunosuppressive
      viruses reduced B cells and T helper cells in the Harderian glands and cecal
      tonsils in response to IBV, and slowed the kinetics and/or reduced the magnitude
      of the mucosal immune response against IBV. We have shown for the first time that
      CAV affects pathogen-specific B cell responses in a mucosal effector site.

PMID- 19166052
TI  - Isolation of 4/91 type of infectious bronchitis virus as a new variant in Japan
      and efficacy of vaccination against 4/91 type field isolate.
AB  - Among field isolates of infectious bronchitis virus (IBV) from recent outbreaks,
      some isolates that were classified into the 4/91 genotype, by analysis of the S1
      gene, have been confirmed to be a new variant in Japan. To elucidate the
      characteristics of these isolates, pathogenicity in chicks and the efficacy of
      vaccines against this new variant were examined. Severe respiratory symptoms were
      observed in 4-day-old specific pathogen free chicks inoculated with a 4/91
      genotype isolate, either JP/Wakayama/2003 or JP/ Iwate/2005; body weights 3 wk
      after inoculation were significantly lower than those of chicks inoculated with a
      4/91 vaccine strain. These 4/91 isolates were neutralized with serum from birds
      immunized with 4/91 vaccine. In a challenge-protection test, five groups of
      chicks were immunized with C78, TM-86w, H120, Kita-1, or 4/91 vaccines and then
      challenged with JP/Iwate/2005 4 wk after vaccination. A protective effect in the
      4/91 and TM-86w vaccine groups was indicated by evaluation of the ciliostasis
      score of the trachea, the respiratory symptom score, and virus isolation from
      trachea swab samples after challenge. The results of this study suggested that
      the 4/91 type of IBV, which is virulent to chicks when compared to vaccine
      strains, has emerged as a new variant in Japan, and vaccines containing the 4/91
      strain or the TM-86w strain could be effective for this variant.

PMID- 19166053
TI  - Virulence of low pathogenicity H7N2 avian influenza viruses from the Delmarva
      peninsula for broiler and leghorn chickens and turkeys.
AB  - The virulence of low pathogenicity (LP) type A H7N2 avian influenza virus (AIV)
      isolates recovered from chickens in Delaware and the eastern shore of Maryland in
      2004 was evaluated. Three-week-old leghorn- and broiler-type chickens and turkeys
      were inoculated via the conjunctival sac with 10(3.5)-10(4.0) 50% embryo
      infections dose (EID50) of virus per bird with A/ chicken/Delaware/Viva/04,
      A/chicken/Delaware/Hobo/04, and A/chicken/Maryland/Minh Ma/04. In broilers, the
      viruses produced respiratory signs, airsacculitis, and microscopic lesions in the
      trachea and lung. In contrast, signs and lesions were less severe in turkeys, and
      they were rarely observed in specific-pathogen-free (SPF) leghorns. In broilers
      and SPF leghorns, AIV peaked on day 3 postinoculation (PI), based on virus
      isolation and real-time reverse transcription-polymerase chain reaction, and
      antigen capture testing. Infection in turkeys peaked on day 7 PI. Serum
      antibodies generally were detected earlier in broilers (day 7 PI) than in turkeys
      or SPF leghorns (day 14 PI) using agar gel immunodiffusion, hemagglutination
      inhibition, and the enzyme-linked immunosorbent assay. A second trial was
      performed to further examine the disease susceptibility of the leghorn chicken
      given the comparatively mild responses noted in the first trial. A 10-fold higher
      dose of 10(4.5)-10(5.0)EID50 per chick given via the conjunctival sac was used.
      In addition, commercial-type leghorns were tested as were chicks from the SPF
      leghorn source. The higher AIV dose resulted in more rapid and consistent rates
      of infection and higher serum antibody responses in both types of leghorn
      chickens. However, as observed in the first trial, clinical signs and microscopic
      lesions in both types of leghorns were infrequent and very mild. These findings
      indicate leghorn-type chickens, which are commonly used for pathogenicity
      assessments because of their availability, may not be the most suitable host for
      evaluating the virulence potential of LP AIV.

PMID- 19166054
TI  - Efficacy of lasalocid against coccidiosis in Chinese ring-necked pheasants.
AB  - Two battery efficacy studies were conducted with field isolates of Eimeria spp.
      from outbreaks of coccidiosis on pheasant-rearing farms in Georgia (GA) and
      Illinois (IL), United States. The coccidian isolates were mixed species
      containing E. phasiani, E duodenalis, and E colchici. Lasalocid (LAS) was tested
      prophylactically at 120 parts per million (ppm) in the feed. Anticoccidial
      activity was assessed, in comparisons between infected and uninfected control
      birds, by the effects on weight gain and oocyst passage. The GA isolate reduced
      weight gain of infected controls by 64% (P < 0.05) during the week after
      inoculation. LAS-treated birds also suffered some depressed gain, but average
      gains were significantly improved (P < 0.05) in comparison with that of the
      infected controls. Fecal oocyst counts of infected controls averaged 10-24 x
      10(6)/day for days 5-11 postinoculation (PI), after which oocyst passage
      declined. Birds given LAS passed 10-20 x 10(6) oocysts on days 5-6 PI, after
      which counts dropped to much lower levels. Oocyst passage was significantly
      reduced (P < 0.05) by LAS treatment on all but days 5 and 6 PI. The IL isolate
      reduced weight gain by 36% in infected controls, relative to uninfected controls
      (P < 0.05). LAS-treated birds also suffered reduced gain, but the gain was
      significantly improved in comparison with the infected controls. Oocyst counts
      averaged 3-9 x 10(6)/day on days 6-14 PI, but were significantly reduced by LAS
      treatment on all but day 6 PI. Thus, LAS was effective in pheasants against the
      tested field isolates of Eimeria spp. and was well tolerated at 120 ppm in the
      feed. However, the level of control was not as high as previously observed.
      Possible explanations for this difference include an emergence of drug resistance
      from prior use of LAS and a differential efficacy of LAS against different
      species of Eimeria used in the studies.

PMID- 19166055
TI  - Ulcerative enteritis-like disease associated with Clostridium perfringens type A
      in bobwhite quail (Colinus virginianus).
AB  - Ulcerative enteritis-like disease due to Clostridium perfringens type A was
      attributed as the cause of mortality in excess of 50% in a flock of 1000, 10-to
      16-wk-old bobwhite quail (Colinus virginianus). Clinical signs in these birds
      ranged from sudden death to listlessness, depression, watery white droppings,
      ruffled feathers, loss of weight, and death in a few days. Necropsy of 30 birds
      revealed multiple deep ulcers of the mucosa throughout the small intestine and
      ceca, some with perforation and subsequent coelomitis (peritonitis). The livers
      in some birds contained white foci of necrosis, and many birds had enlarged and
      congested spleens. Microscopic lesions included multifocal severe
      fibrinosuppurative ulcerative enteritis associated with large numbers of rod
      shaped gram-positive bacteria, and necrotizing hepatitis with or without rod
      shaped bacteria. Anaerobic culturing of the intestine and liver yielded pure
      cultures of C. perfringens. The C perfringens isolates were of genotype A and
      were polymerase chain reaction-positive for alpha toxin and for cpb2, the
      structural gene for beta2 toxin. Repeated attempts to isolate C colinum by using
      a specialized medium containing 8% horse plasma were not fruitful, suggesting
      that the enteritis and hepatitis in these birds were produced by C pefringens.
      Retrospective examination of records of quail submissions to the California
      Animal Health and Food Safety Laboratory System over 16 yr revealed at least nine
      quail submissions in which isolation of C. perfringens from the liver, intestine,
      or both was associated with ulcerative enteritis and hepatitis in quail. This is
      the first description of ulcerative enteritis-like disease in quail associated
      with C perfringens. Final conclusions await experimental reproduction of the
      disease.

PMID- 19166056
TI  - The role of mycoplasmas in a conservation project of the lesser kestrel (Falco
      naumanni).
AB  - The lesser kestrel (Falco naumanni) is one of the most endangered bird species in
      Europe, and a captive breeding and reintroduction project was established. A
      breeding project is vulnerable to pathogens, e.g., mycoplasmas, reducing the
      reproductive success and carrying the risk to release pathogens with the birds to
      the wild. Therefore, 18 infertile eggs and 43 dead in shell embryos of the
      breeding project, as well as 27 nestlings and 34 adult birds of the captive and
      three different free-ranging populations were investigated for the occurrence of
      mycoplasmas by culture and a Mycoplasma genus-specific polymerase chain reaction.
      All eggs, embryos, and hand-reared nestlings from the captive group were
      negative. In contrast, all parent-reared nestlings and 88% of the adults were
      positive. Mycoplasma falconis and unidentifiable mycoplasmas were detected in all
      groups. Mycoplasma buteonis was found in the captive and only in two of the three
      free-ranging populations. Sequencing the 16S rRNA gene of six randomly selected
      unidentified isolates showed that five isolates were similar and most likely had
      been found previously in a falcon from Germany. The remaining isolate
      demonstrated a very high homology to unidentified Mycoplasma isolates obtained
      previously from semen samples of raptors. The results suggest that these isolates
      might represent two new species. Mycoplasmas seem not to play a major role as
      pathogens in the breeding project, and there is no evidence that releasing birds
      poses a risk to the free-ranging population with regard to mycoplasmas. The study
      seems to be the first to describe the occurrence and role of mycoplasmas in the
      lesser kestrel.

PMID- 19166057
TI  - Enhancement of resistance to coccidiosis and necrotic enteritis in broiler
      chickens by dietary muscadine pomace.
AB  - Muscadine pomace (MP), a by-product of the production of wine and juice from
      Vitis rotundifolia, was dried and tested in chickens for effects on primary
      resistance to coccidiosis, development of protective immunity after vaccination
      with live coccidia, and resistance to necrotic enteritis (NE) caused by the joint
      action of Clostridium perfringens and coccidia. To test primary resistance to
      coccidiosis, 2-wk-old chicks were given 2% or 5% MP in the diet and inoculated
      with Eimeria acervulina and E. maxima. Birds given MP at either level had
      significantly (P < 0.05) lower lesion scores at 7 days postinoculation, in
      comparison with control birds, although weight gains were statistically similar.
      Broiler chickens were given 2% or 5% MP and grown to 42 days to test the
      palatability of MP. Birds given 2% MP in feed grew similarly to untreated
      controls, but birds given 5% had poorer average live weight. This suggested a
      negative effect on feed intake at the higher level. The effects of dietary 0.5%
      or 2.0% MP on immune protection were tested after live coccidiosis vaccination in
      the hatchery. Chicks were removed from each pen at 21 days of age and challenged
      with E acervulina, E. maxima, and E. tenella. Resistance to infection was
      improved by MP as suggested by significantly (P < 0.05) lower lesion scores 7
      days postchallenge, and improved weight gains in comparison with immunized
      control birds that did not receive MP. At 42 days of age, birds given MP had
      higher average live weights than controls, although feed efficiency was not
      affected. An established model was used to study the effect of MP on NE in
      broiler chickens. Chicks were inoculated with live coccidia at 14 days of age and
      dosed orally with live cultures of C perfringens on day 19, day 20, and day 21.
      Enteritis caused 48% mortality in the first study and 67% mortality in the second
      study. Dietary MP at 0.5-2.0% significantly (P < 0.05) reduced mortality in both
      experiments; improved weight gain relative to the unmedicated, infected control;
      and reduced lesion scores at necropsy. Overall, the results of six experiments
      suggested that MP given in the diet at 0.5% or higher had a positive effect on
      primary resistance and development of acquired resistance to two severe
      intestinal diseases in chickens.

PMID- 19166058
TI  - Detection of five avian Eimeria species by species-specific real-time polymerase
      chain reaction assay.
AB  - To detect five different avian Eimeria species, we applied the SYBR Green-based
      real-time polymerase chain reaction (PCR) assay for the diagnosis of field
      isolated parasites by using their individual species-specific primer sets. The
      primer sets were originally designed for Eimeria acervulina, E brunetti, E
      necatrix, and E tenella based on the sequence of the internal transcribed spacer
      1 region of ribosomal DNA, whereas for E. maxima the primer sets were derived
      from sequences reported previously. The detection limit of these assays was
      defined at 10(2) or 10(1) oocysts depending on species. Melting curves from the
      real-time PCR assay showed that each species has a single peak and specific
      melting temperature value. Fecal samples from 32 poultry farms, which were
      endemic for coccidiosis, were examined using this assay. The data showed that E.
      brunetti was found in 21 farms, E maxima and E. necatrix in 16 farms, E. tenella
      in 12 farms, and E. acervulina in eight farms. This survey revealed that E
      brunetti was highly prevalent in Japan. This technique is not only easy and rapid
      but also available to detect Eimeria species specifically; therefore, it can be a
      valuable tool for diagnostic work for chicken coccidiosis.

PMID- 19166059
TI  - Cellular assessment of crop lymphoid tissue from specific-pathogen-free white
      leghorn chickens after Salmonella enteritidis challenge.
AB  - The crop may be an important site along the upper alimentary tract in which a
      humoral immune response against Salmonella Enteritidis (SE) is elicited locally.
      The mucosal immune response within the crop (ingluvies) of specific-pathogen-free
      (SPF) white leghorn (WL) chickens against SE was investigated. Three trials were
      conducted using SPF WL pullets at age 5-6 wk. Trial 1 consisted of 77 birds
      evaluated for 10 wk post-SE infection (pi), trial 2 was composed of 72 birds
      monitored through 8 wk pi, and trial 3 was made up of 30 birds assessed for 5 wk
      pi. Birds were challenged per os with 10(8) colony-forming units/ml SE phage type
      13. Crop lavage samples, crop tissues, ceca, and/or liver-spleen were collected
      preinfection and then at weekly intervals post-SE infection. Bacteriologic
      examination of cecal contents and/or liver-spleen occurred weekly to monitor
      progression of SE infection. Crop lavages were analyzed for SE-lipopolysaccharide
      (LPS)-specific immunoglobulin A (IgA) by enzyme-linked immunosorbent assay to
      assess humoral immune response. General histologic staining (hematoxylin and
      eosin [H&E] and methyl green-pyronin [MGP]) and immunohistochemical (IHC)
      staining (monoclonal antibodies CD45 and Bu-1) were applied to serial sections of
      crop to evaluate lymphoid tissue via light microscopy, to grade isolated lymphoid
      follicles (ILFs) by using score 0 (minimal, < 50 microm in diameter) to score 5
      (sizable, > 200 microm in diameter) scale, and to characterize the cellular
      population of ILFs. Results revealed that cecum samples and liver-spleen samples
      were 100% SE culture positive at 1 wk pi, and then the percentage of SE positives
      progressively declined over time. Markedly increased crop SE-LPS-specific IgA
      antibodies were detected in crop samples by 2-3 wk pi, and the humoral response
      remained elevated above week 0 baseline for the duration of each trial. Crop ILFs
      of score 3 to 5 were observed in H&E-stained tissues, with an increased
      proportion of ILFs in post-SE-infected crops vs. uninfected. MGP staining showed
      plasma cells scattered within and at the periphery of ILFs. IHC staining revealed
      CD45 (pan-leukocyte) and Bu-1 (B-lymphocyte)-positive cells within crop ILFs. The
      chicken crop seems to be an organ in which lymphoid tissue may arise in response
      to enteric SE infection, and a site in which a humoral response may be generated
      against the SE pathogen.

PMID- 19166060
TI  - Molecular characterization of Iranian infectious bursal disease viruses.
AB  - This study was conducted to characterize nine infectious bursal disease virus
      (IBDV) isolates from Iran. A reverse transcriptase-polymerase chain reaction (RT
      PCR) procedure was used to amplify a 743-bp fragment of the VP2 gene
      hypervariable region from IBDV field isolates. Amplified VP2 fragments of the
      nine IBDV isolates were sequenced and compared with published sequences of IBDV
      strains from Iran and around the world, and their phylogenetic relationships were
      analyzed. Three isolates demonstrated close relation to classical attenuated
      strains of IBDVs, and six isolates showed sequences common in European and Asian
      strains of very virulent IBDVs (vvIBDVs). Four nucleotide changes--802A, 934A,
      940A, and 1366A--were common in all Iranian vvIBDVs except in one isolate. Amino
      acid sequences of three Iranian vvIBDVs were 100% identical and resembled vvIBDV
      strains from European (UK661), Asian (HK46, GZ96), and Iranian origins (IR01,
      SDH1). Some unique amino acid substitutions after major hydrophilic peak A in
      Iranian vvIBDV field isolates were observed: 231S-L, 231S-P, and 233N-K.
      Phylogenetic analysis showed that the Iranian vvIBDVs were closely related to
      European and Asian vvIBDVs. Further comprehensive investigations will provide
      more information on the distribution, variability, and phylogenetic relationships
      of different IBDVs isolated in Iran and other parts of the world.

PMID- 19166061
TI  - Infectious bursal disease subunit vaccination.
AB  - Infectious bursal disease virus (IBDV) is the causative agent of infectious
      bursal disease, a nosologic entity with global economic importance in poultry.
      The viral protein 2 (VP2) is recognized as the virus' major antigenic protein.
      The goal of this study was to generate yeast (Pichia pastoris)-based protein
      expression from the VP2 gene of the Edgar strain of IBDV and from the
      hypervariable region of the VP2 gene (hvVP2) to test the protection afforded
      against virulent IBDV challenge when inoculated in chickens. The genetic material
      used for protein expression was obtained from paraffin-embedded tissue. Specific
      pathogen-free chickens were vaccinated with the expressed products and challenged
      with the homologous strain (Edgar). After challenge, no morbidity or mortality
      was observed in the birds vaccinated with the whole VP2, compared with 30%
      morbidity and mortality in the hvVP2-vaccinated birds and with 90% morbidity and
      60% mortality in the unvaccinated, challenged controls. Immunohistochemistry
      detection of the challenge virus and some extent of bursal damage were observed
      in all challenged birds, indicating active replication of the challenge virus
      despite vaccination. As determined by bursal index values, the protection against
      postchallenge bursal atrophy was significantly higher (P < 0.05) in the VP2 group
      than in the unvaccinated and hvVP2-vaccinated birds. Overall, the results
      indicated that paraffin-embedded tissue can be used as a source of genomic
      material for transgenic protein expression, that Pichia pastoris-expressed VP2
      retains its immunogenicity, and that VP2 subunit vaccination conferred partial
      protection to challenge; it protected against clinical signs and death but not
      against IBDV infection.

PMID- 19166062
TI  - Seroprevalence of avian reovirus in egg-laying chicken flocks in China.
AB  - In the present study, the epidemiologic status of avian reovirus (ARV) infections
      was investigated from egg-laying chicken flocks in China with an enzyme-linked
      immunosorbent assay (ELISA) kit. Because the chickens were not vaccinated against
      ARV, antibodies were attributed to the infection. Antibodies specific to ARV were
      found in more than 92% (542/587) of the average positivity and ranged from 30% to
      100% in different chicken population. A virus, designated HB06, was isolated from
      flocks with suspicious ARV infections. Sequence analysis of the S1 gene revealed
      that strain HB06 was closely related with the most ARVs with less than 2%
      nucleotide divergence, and the homology was highest with the vaccine strain
      S1133, with a 98.97% nucleotide identity. The potential significance of
      vaccination against ARV in egg-laying chicken flocks in China is also discussed.

PMID- 19166063
TI  - Occurrence and characterization of Campylobacter in the Brazilian production and
      processing of broilers.
AB  - Twenty-two commercial broiler flocks and their carcasses, totaling 546 samples
      (450 collected from a poultry farm and 96 from a slaughterhouse), were surveyed
      for the presence of Campylobacter. The positive results for Campylobacter among
      the analyzed samples were homogeneous, yielding 81.8% for cecal droppings, 80.9%
      for feces, and 80.4% for cloacal swabs. Pre-enrichment and direct plating showed
      that 77.85% and 81.8% of cloacal swabs, respectively, were positive for
      Campylobacter compared to 99.0% and 97.9% of carcasses testing positive with the
      pre-enrichment and direct plating methods. The Campylobacter count averaged 7.0
      log10 colony-forming units (CFU)/g in cecal droppings, 5.15 log10 CFU/carcass
      after defeathering, and 4.24 log10 CFU/carcass after chilling. The samples were
      identified by the API Campy system as Campylobacter jejuni subsp. jejuni (68.8%),
      Campylobacter coli (8.3%), Campylobacter jejuni subsp. doylei (6.3%),
      Campylobacter upsaliensis (4.2%), and Campylobacter fetus subsp. fetus (2.1%).
      The analyzed broiler flocks were positive for Campylobacter in 81.8% of the
      cases, thus characterizing the occurrence of this pathogen in a broiler-producing
      region in southern Brazil. These results highlight the importance of programs
      targeted at the reduction of Campylobacter in poultry products, in order to
      minimize the risks for consumers.

PMID- 19166064
TI  - Molecular characterization and typing of enrofloxacin-resistant clinical isolates
      of Mycoplasma gallisepticum.
AB  - Emergence of resistance to fluoroquinolones is mainly due to chromosomal
      mutations in genes encoding the subunits of the drug's target enzymes, DNA gyrase
      and topoisomerase IV, which are essential for DNA replication. The quinolone
      resistance-determining regions (QRDRs) of these genes were characterized in 25
      Mycoplasma gallisepticum strains isolated from commercial poultry flocks during
      1997-2007, which exhibited different levels of susceptibility to
      fluoroquinolones. All enrofloxacin-resistant isolates harbored amino acid
      substitutions in the QRDRs of each of three proteins (GyrA, GyrB, and ParC).
      Molecular typing of those strains by random amplification of polymorphic DNA and
      gene-targeted sequencing supports ongoing, stepwise selection of resistant
      strains from the existing reservoir of susceptible M. gallisepticum strains.

PMID- 19166065
TI  - Reduced serologic response to avian influenza vaccine in specific-pathogen-free
      chicks inoculated with Cryptosporidium baileyi.
AB  - Immunosuppression in chickens as a consequence of Cryptosporidium baileyi
      infection may compromise the effectiveness of vaccination for control of avian
      influenza (AI) H5N1. In a 13-wk study using 260 specific-pathogen-free chicks,
      immunological response and bursa weight:body weight ratios following vaccination
      against AI strain H5N1 were compared between uninfected and C baileyi-infected
      birds. The four experimental treatments were the following: infection with C.
      baileyi (5 x 10(5) oocysts dosed orally on day 0); C baileyi infection +
      vaccination against H5N1 (0.3 ml inactivated vaccine administered subcutaneously
      on day 7 and day 21; CB+VAC); vaccination only (VAC); and sham
      infection/vaccinations using sterile distilled water (control). At weekly
      intervals serum samples were analyzed by hemagglutination inhibition assay (HI),
      and five chicks/group were euthanatized for determination of bursa weights. In
      all but week 8, proportional bursa weights (bursa weight/body weight) were lower
      for CB+VAC chicks than for VAC chicks (i.e., the bursa index was below 1.0;
      average 0.81). Throughout the 13 wk, HI titres were lower (P < 0.01) in CB+VAC
      than in the VAC group, and compared with VAC, chicks in CB+VAC had a slightly
      shorter period of negative seroconversion. These data indicate bursal atrophy and
      immunosuppressive effects of C. baileyi infection on day-old chicks vaccinated
      against AI strain H5N1 and suggest that C. baileyi infection in chicks may
      increase the host susceptibility to AI virus.

PMID- 19166066
TI  - Prevalence of antibodies to different avian paramyxoviruses in commercial poultry
      in the United States.
AB  - Avian paramyxoviruses (APMVs) other than Newcastle disease virus have been
      isolated from feral avian species and have the potential to cause clinical
      disease. The objective of this study was to investigate the APMV antibody
      prevalence in commercial poultry settings. Sera from 100 commercial, layer-type
      and broiler-type (broiler-breeder and broiler) chicken flocks were analyzed on a
      random basis. Pooled serum samples from each flock were tested for the presence
      of antibodies to APMV-1, -2, -3, -4, -6, -7, -8, and -9 by hemagluttination
      inhibition (HI) test. Reactions with HI titers > or = 1:64 were shown by APMV-1
      (71%), APMV-2 (15%), APMV-3 (35%), APMV-4 (26%), APMV-6 (45%), APMV-7 (27%), APMV
      8 (31%), and APMV-9 (48%). In the presence of a high HI titer for APMV-1 (1024),
      we obtained positive HI titers for most of the other APMV subtypes, thus
      implicating that sensitive techniques need to be developed to detect the
      prevalence of these subtypes in commercial poultry.

PMID- 19166067
TI  - Facial cellulitis induced in chickens by Mycoplasma gallisepticum bacterin and
      its treatment.
AB  - Ten-to-14-day-old replacement chickens were vaccinated subcutaneously in the neck
      with a Mycoplasma gallisepticum bacterin. A few days later, 40% of the flock
      developed cellulitis of the head. Birds were submitted for diagnostic
      investigation between 4 and 6 wk of age. Histology revealed lesions in the
      subcutis consistent with oil-emulsified vaccine/bacterin reaction. No significant
      bacteria were isolated from the lesions. Birds were treated with 1 mg of methyl
      prednisol acetate intramuscularly. Improvement was noted as early as 12 hr
      posttreatment. One week after treatment only 1%-2% of the flock still had facial
      cellulitis.

PMID- 19166068
TI  - Natural infection with Cryptosporidium galli in canaries (Serinus canaria), in a
      cockatiel (Nymphicus hollandicus), and in lesser seed-finches (Oryzoborus
      angolensis) from Brazil.
AB  - Proventricular infection by Cryptosporidium sp. or Cryptosporidium galli has been
      associated with mortality, weight loss, diarrhea, and pasty feces. The purpose of
      this study is to report the occurrence of natural C galli infection in canaries
      (Serinus canaria), in a cockatiel (Nymphicus hollandicus), and in lesser seed
      finches (Oryzoborus angolensis) with clinical complaints of apathy and sporadic
      mortality. Screening for Cryptosporidium spp. using microscopic examination of
      fecal samples and stained smears, histopathology, and nested polymerase chain
      reaction for actin gene and 18S ribosomal RNA gene following sequencing of
      amplified fragments allowed for the identification of C galli. To the best of our
      knowledge, this is the first report of C galli in birds in Brazil and the first
      report of this species in lesser seed-finches.

PMID- 19166069
TI  - An outbreak of sarcocystosis in psittacines and a pigeon in a zoological
      collection in Brazil.
AB  - This report describes an outbreak of acute pulmonary sarcocystosis in different
      species of captive psittacines and in a Luzon bleeding-heart pigeon (Gallicolumba
      luzonica) in a zoological collection in Brazil. A majority of the birds were
      found dead and had exhibited no previous clinical signs. Grossly, pulmonary
      congestion and edema were the most-common findings. Enlarged and congested livers
      and spleens were also frequently observed. Microscopically, there was edema,
      fibrin exudation, congestion, and perivascular and interstitial lymphoplasmacytic
      infiltration associated with numerous sinuous schizonts of Sarcocystis sp. in the
      lungs. Mild to moderate myocarditis, hepatitis, splenitis, and interstitial
      nephritis were also observed in the birds. Immunohistochemistry confirmed
      Sarcocystis sp. in the capillaries of lungs, hearts, livers, and spleens of most
      of the birds, but also in the pancreas, kidney, intestine, proventriculus, and
      brain of a few birds. The probable source of Sarcocystis sp. in these birds was
      the wild opossum (Didelphis albiventris), a common inhabitant of a local forest
      that surrounds the Belo Horizonte Zoo (Fundacao Zoo-Botanica). This is the first
      documentation of Sarcocystis infection in psittacines and a pigeon from Brazil.

PMID- 19166070
TI  - Concurrent aspergillosis and ascites with high mortality in a farm of growing
      broiler chickens.
AB  - Two flocks of broiler chickens aged 15 to 30 days presented respiratory signs
      such as dyspnea and up to 25% mortality. These were the only two flocks in the
      farm where a bed of sunflower shells was used instead of the rice-hull bedding
      used in other flocks. At necropsy, severe ascites, right heart hypertrophy,
      pulmonary congestion, and extensive multifocal granulomatous pneumonia were
      recorded. Histopathologic examination revealed chronic multifocal mycotic
      granulomatous pneumonia. Aspergillus fumigatus was identified by microbiologic
      study from pulmonary specimens. After disinfecting the floor and changing the
      bedding, no clinical signs were recorded in the farm. Severe chronic
      granulomatous pneumonia caused by A. fumigatus in the chickens of the present
      study may have caused hypoxia, leading to pulmonary hypertension, heart failure,
      and ascites.

PMID- 19166071
TI  - Pemphigus-like immune-mediated dermatosis in a Korean native black-bone fowl.
AB  - A 3-yr-old female Korean native black-bone fowl weighing 1 kg presented with
      refractory dermatosis characterized by hyperkeratosis and alopecia on the head,
      neck, and scapular region. Antibiotic therapy before referral had not reduced the
      severity of lesions. Histopathologic findings revealed hyperkeratosis,
      acantholysis, heterophil infiltration, and ballooning degeneration in the
      epidermis. Immunohistochemical analysis showed immunoglobulin G deposits in the
      intercellular spaces of the intermediate layer of the epidermis. Based on these
      observations, this case was diagnosed as a pemphigus-like immune-mediated
      dermatosis. The administration of prednisolone eliminated the lesions, and the
      feathers grew back partially.

PMID- 19166072
TI  - Professional civic involvement through membership on the Alabama Board of
      Nursing.

PMID- 19166073
TI  - Marjolin's ulcer.

PMID- 19166074
TI  - Raising awareness about radon and your health.

PMID- 19166075
TI  - Happiness at work.

PMID- 19166076
TI  - Human papillomavirus: HPV information for clinicians.

PMID- 19166078
TI  - AO 2008: a year of positive momentum.

PMID- 19166077
TI  - Frailty: the looming epidemic.

PMID- 19166079
TI  - Daniel N. Uditsky: our international president for 2009.

PMID- 19166080
TI  - Show me the money!

PMID- 19166081
TI  - An overview of lasers in dentistry, continued.

PMID- 19166082
TI  - The use of lasers in periodontal therapy.

PMID- 19166083
TI  - Lasers in prosthodontics: clinical realities of a dental laser in a prosthodontic
      practice.

PMID- 19166084
TI  - The use of lasers for cleaning and disinfecting of the root canal system.

PMID- 19166085
TI  - What laser does your practice need? Advantages, considerations, and practice
      integration of laser dentistry.
AB  - The use of lasers in dentistry has expanded and improved some treatment options
      for those clinicians who have adopted the technology. As with all dental
      materials and instruments, the practitioner must use clinical experience, receive
      proper training, become very familiar with the operating manual, and proceed
      within the scope of his or her practice. The potential purchaser should carefully
      analyze the style and type of the practice to decide how useful the device could
      be. Moreover, attending introductory courses, seminars, and presentations, such
      as those at the aforementioned Academy of Laser Dentistry's Annual Conference, or
      at various state and national scientific sessions, are essential before buying.
      Because of the varied composition of human tissue and the differing ways that
      laser energy is absorbed, there is no single perfect laser. However, our patients
      continue to agree that the dental laser is a wonderful instrument.

PMID- 19166086
TI  - The Gerald and Reesa Niznick Faculty Clinic.

PMID- 19166087
TI  - The changing landscape of state legislation and expanded HIV testing.

PMID- 19166089
TI  - Comparing the costs of HIV screening strategies and technologies in health-care
      settings.
AB  - OBJECTIVES: In 2006, the Centers for Disease Control and Prevention (CDC)
      recommended routine human immunodeficiency virus (HIV) screening for people aged
      13 to 64 years in all U.S. health-care settings. Earlier recommendations focused
      on those at high risk for HIV and included more extensive pretest counseling. HIV
      screening may also involve either rapid or conventional testing. The purpose of
      this research was to estimate the costs of these different testing procedures and
      the cost per HIV-infected patient correctly receiving test results in three
      health-care scenarios that illustrated these policy differences. METHODS: The
      study estimated the costs of rapid and conventional HIV testing in the following
      scenarios: (1) sexually transmitted disease (STD) clinic counseling and testing
      (CT), (2) STD clinic screening, and (3) emergency department (ED) screening.
      Costs were estimated from the provider perspective in 2006 dollars. A decision
      analytic model was developed to estimate the cost per HIV-infected patient
      notified of test results using the two testing procedures in the three scenarios.
      RESULTS: Although the complete rapid testing procedure was more expensive than
      conventional testing, the cost per HIV-infected patient receiving test results
      was lower for the rapid test compared with conventional testing in all scenarios.
      Per-patient costs of receiving results were lowest in the ED screening scenario
      and highest in the STD CT scenario. These costs were sensitive to changes in test
      costs, HIV prevalence, and return rates following conventional tests. CONCLUSION:
      HIV screening in general health-care settings is economically feasible,
      particularly with rapid tests that lower the cost of HIV-infected patients
      receiving their test results.

PMID- 19166090
TI  - Results from a multiple morbidities testing program offering rapid HIV testing
      bundled with hepatitis and sexually transmitted infection testing.
AB  - OBJECTIVES: Bundling human immunodeficiency virus (HIV) testing with tests for
      other infectious diseases such as hepatitis C, syphilis, or gonorrhea has been
      proposed as a method to recruit at-risk individuals into HIV testing. The
      objectives of this study were to determine (1) the types of at-risk clients who
      choose the rapid vs. standard HIV test when bundled with hepatitis and sexually
      transmitted infection (STI) tests, and (2) whether clients receiving a rapid HIV
      test are more likely to return on time for hepatitis and STI test results.
      METHODS: We recruited individuals from drug treatment programs, methadone
      maintenance programs, needle-exchange programs, a community-based agency serving
      the gay and lesbian community, and the Center for Behavioral Research and
      Services' office-based testing facility at California State University, Long
      Beach from January 2005 through November 2007. RESULTS: A total of 2,031 clients
      from a multiple morbidities testing program in Long Beach, California, were
      tested between January 2005 and November 2007. For clients receiving hepatitis
      and STI testing, the majority chose the standard HIV test. Clients who received a
      rapid HIV test returned in significantly fewer days than clients who received a
      standard HIV test. Injection drug users and sex traders were more likely to
      choose the standard HIV test and more likely to fail to return for test results
      on time. CONCLUSION: The rapid HIV test, in conjunction with hepatitis and STI
      tests, results in clients being more likely to return on time for hepatitis and
      STI results. Public health efforts should focus on acquainting high-risk clients
      with rapid HIV testing.

PMID- 19166088
TI  - Prevalence and correlates of unknown HIV infection among patients seeking care in
      a public hospital emergency department.
AB  - OBJECTIVES: Screening for human immunodeficiency virus (HIV) infection in the
      emergency department (ED) has been proposed as an effective approach to increase
      early HIV diagnosis. To evaluate the potential for the implementation of routine
      screening, we determined the prevalence of unknown HIV infection among patients
      being seen in an urban public hospital ED. METHODS: We conducted a cross
      sectional study among patients presenting to the San Francisco General Hospital's
      ED during March 2007. We reviewed patients' medical records to determine HIV
      infection status. In patients with unknown or negative HIV-infection status, we
      tested de-identified remnant blood specimens by HIV-antibody and nucleic-acid
      assays. We used a sensitive/less sensitive testing algorithm to determine the
      duration of HIV infection. RESULTS: During the study period, 1,820 patients had
      blood collected for clinical evaluation. Of those patients, 146 (8.0%) were known
      to be HIV-infected. Among the remaining 1,674 patients with unknown HIV-infection
      status, HIV-infection prevalence was 0.9% (15 of 1,674, 95% confidence interval
      [CI] 0.55, 1.47). In addition, one case of acute HIV infection (HIV-antibody
      negative, HIV RNA detected) was identified. Patients with unknown HIV infection
      vs. those who were uninfected were more likely to be homeless (odds ratio [OR] =
      3.89, 95% CI 1.32, 11.45, p<0.05) and 18 to 30 years of age (OR=3.15, 95% CI
      1.03, 9.61, p<0.05). CONCLUSIONS: In a sample of patients visiting a county ED,
      the relative prevalence of unknown HIV infection (10%) was modest and less than
      national estimates (25%). Acutely HIV-infected patients might account for a
      significant proportion of those with unknown HIV infection in an ED setting.

PMID- 19166091
TI  - Feasibility of using computer-assisted interviewing to enhance HIV test
      counseling in community settings.
AB  - OBJECTIVES: Significant advances in the treatment of human immunodeficiency virus
      (HIV)/acquired immunodeficiency syndrome (AIDS) place a premium on early
      detection and linkage to care. Recognizing the need to efficiently yet
      comprehensively provide HIV counseling, we assessed the feasibility of using
      audio computer-assisted self-inventory (A-CASI) in a community-based HIV
      counseling and testing facility. METHODS: A convenience sample of 50 adults
      presenting for HIV testing was recruited to complete an 85-item computerized HIV
      Assessment of Risk Inventory (HARI) containing domains of demographics, sexual
      behaviors, alcohol and substance use, emotional well-being, past experiences with
      HIV testing, and attitudes about taking HARI. RESULTS: Client acceptance rate was
      limited by the completion time outlined during the intake process. However, the
      majority of respondents who completed HARI felt that it took only a short to
      moderate time to complete and was easy to understand. A majority also reported a
      preference for using a computerized format in the future. Further, HARI
      identified a number of risk-taking behaviors, including unprotected anal sex and
      substance use prior to past sexual encounters. Additionally, more than half of
      the sample reported moderate to severe depressive symptoms. CONCLUSIONS: Those
      respondents who had time to complete the survey accepted the A-CASI interview,
      and it was successful at identifying a substantial level of risk-taking
      behaviors. A-CASI has the potential to guide HIV counselors in providing risk
      reduction counseling and referral activities. However, results suggested the need
      to shorten the instrument, and further studies are needed to determine
      applicability in other HIV testing sites.

PMID- 19166092
TI  - Implementation of rapid HIV testing programs in community and outreach settings:
      perspectives from staff at eight community-based organizations in seven U.S.
      cities.
AB  - OBJECTIVES: The goals of this research were to evaluate perceptions of staff
      about the effectiveness of methods used by eight community-based organizations
      (CBOs) to implement human immunodeficiency virus (HIV) counseling and rapid
      testing in community and outreach settings in seven U.S. cities, and to identify
      operational challenges. METHODS: A survey was administered to CBO staff to
      determine their perceptions about the effectiveness of methods used to select
      testing venues, promote their testing programs, recruit people for testing,
      provide test results, and link HIV-positive people to health care. Using a Likert
      scale, respondents rated the effectiveness of methods, their agreement with
      statements about using mobile testing units (MTUs) and rapid HIV test kits, and
      operational challenges. RESULTS: Most respondents perceived the methods they used
      for selecting testing venues, and particularly using recommendations from people
      receiving testing, to be effective. Most respondents also thought their
      promotional activities were effective. Respondents believed that using MTUs
      improved their capacity to reach high-risk individuals, but that MTUs were
      associated with substantial challenges (e.g., costs to purchase and maintain
      them). Programmatic challenges included training staff to provide counseling and
      testing, locating and providing confirmatory test results to people with reactive
      rapid tests, and sustaining testing programs. CONCLUSIONS: CBO staff thought the
      methods used to select venues for HIV testing were effective and that using MTUs
      increased their ability to provide testing to high-risk individuals. However,
      using MTUs was expensive and posed logistical difficulties. CBOs planning to
      implement similar programs should take these findings into consideration and pay
      particular attention to training needs and program sustainability.

PMID- 19166093
TI  - Cost-effectiveness of finding new HIV diagnoses using rapid HIV testing in
      community-based organizations.
AB  - OBJECTIVE: We assessed the cost-effectiveness of determining new human
      immunodeficiency virus (HIV) diagnoses using rapid HIV testing performed by
      community-based organizations (CBOs) in Kansas City, Missouri, and Detroit,
      Michigan. METHODS: The CBOs performed rapid HIV testing during April 2004 through
      March 2006. In Kansas City, testing was performed in a clinic and in outreach
      settings. In Detroit, testing was performed in outreach settings only. Both CBOs
      used mobile testing vans. Measures of effectiveness were the number of HIV tests
      performed and the number of people notified of new HIV diagnoses, based on rapid
      tests. We retrospectively collected program costs, including those for personnel,
      test kits, mobile vans, and facility space. RESULTS: The CBO in Kansas City
      tested a mean of 855 people a year in its clinic and 703 people a year in
      outreach settings. The number of people notified of new HIV diagnoses was 19
      (2.2%) in the clinic and five (0.7%) in outreach settings. The CBO in Detroit
      tested 976 people a year in outreach settings, and the number notified of new HIV
      diagnoses was 15 (1.5%). In Kansas City, the cost per person notified of a new
      HIV diagnosis was $3,637 in the clinic and $16,985 in outreach settings. In the
      Detroit outreach settings, the cost per notification was $13,448. CONCLUSIONS:
      The cost of providing a new HIV diagnosis was considerably higher in the outreach
      settings than in the clinic. The variation can be largely explained by
      differences in the number of undiagnosed infections among the people tested and
      by the costs of purchasing and operating a mobile van.

PMID- 19166094
TI  - Rapid HIV testing in transgender communities by community-based organizations in
      three cities.
AB  - OBJECTIVES: This article describes the demographic and behavioral
      characteristics, human immunodeficiency virus (HIV) testing history, and results
      of HIV testing of transgender (TG) people recruited for rapid HIV testing by
      community-based organizations (CBOs) in three cities. METHODS: CBOs in Miami
      Beach, Florida, New York City, and San Francisco offered TG people rapid HIV
      testing and prevention services, and conducted a brief survey. Participants were
      recruited in outreach settings using various strategies. The survey collected
      information on demographic characteristics, HIV risk behaviors, and HIV testing
      history. RESULTS: Among 559 male-to-female (MTF) TG participants, 12% were newly
      diagnosed with HIV infection. None of the 42 female-to-male participants were
      newly diagnosed with HIV. A large proportion of MTF TG participants reported high
      risk behaviors in the past year, including 37% who reported unprotected receptive
      anal intercourse and 44% who reported commercial sex work. Several factors were
      independently associated with increased likelihood of being newly diagnosed with
      HIV infection among MTF TG participants, including having a partner of unknown
      HIV status in the past year; being 20-29 or > or = 40 years of age; having last
      been tested for HIV more than 12 months ago; and having been recruited at the New
      York City site. CONCLUSIONS: Based on the high proportion of undiagnosed HIV
      infection among those tested, TG people represent an important community for
      enhanced HIV testing and prevention efforts. MTF TG people should be encouraged
      to have an HIV test at least annually or more often if indicated, based upon
      clinical findings or risk behaviors. Efforts should continue for developing novel
      strategies to overcome barriers and provide HIV testing and prevention services
      to TG people.

PMID- 19166095
TI  - HIV risk behaviors and testing history in historically black college and
      university settings.
AB  - OBJECTIVES: From 2001 through 2005, African Americans accounted for the largest
      percentage of new cases of human immunodeficiency virus (HIV)/ acquired
      immunodeficiency syndrome (AIDS) in all age categories, especially among people
      aged 13 to 24 years. Although students attending historically black colleges and
      universities (HBCUs) report many of the behaviors that promote HIV transmission,
      their risk behaviors and HIV testing practices have not been well-characterized.
      We compared the demographic and behavioral characteristics of people who have
      been previously tested for HIV with those of people tested for the first time in
      this demonstration project to increase HIV testing at HBCUs. METHODS: The Centers
      for Disease Control and Prevention and collaborating partners conducted rapid HIV
      testing and behavioral surveys at HBCUs in Arkansas, Georgia, Mississippi, and
      Washington, D.C., from January 2005 to April 2007. We recruited a convenience
      sample of students and community members at different campus venues including
      student health centers, dormitories, and student activity centers. RESULTS: Our
      analysis included 5,291 people, 42% of whom reported they had never been tested
      for HIV. People who had been tested in the past were more likely to be older,
      believe they were at high risk for infection, have visited a health-care
      facility, and report behaviors that increased their risk of HIV infection.
      CONCLUSION: Respondents who believed they were at increased risk for HIV
      infection or reported behaviors that increased their risk for infection were more
      likely to have been tested for HIV. Future research should compare actual vs.
      perceived risk for HIV infection and contrast how each impacts HIV testing.

PMID- 19166096
TI  - Incorporating rapid HIV testing into partner counseling and referral services.
AB  - OBJECTIVES: Partner counseling and referral services (PCRS) provide a unique
      opportunity to decrease transmission of human immunodeficiency virus (HIV) by
      notifying sex and drug-injection partners of HIV-infected individuals of their
      exposure to HIV. We incorporated rapid HIV testing into PCRS to reduce barriers
      associated with conventional HIV testing and identify undiagnosed HIV infection
      within this high-risk population. METHODS: From April 2004 through June 2006, HIV
      infected people (index clients) were interviewed, and their partners were
      notified of their potential exposure to HIV and offered rapid HIV testing at six
      sites in the United States. The numbers of index clients participating and the
      numbers of partners interviewed and tested were compared by site. Descriptive and
      bivariate analyses were performed. RESULTS: A total of 2,678 index clients were
      identified, of whom 779 (29%) provided partner locating information. A total of
      1,048 partners were elicited, of whom 463 (44%) were both interviewed and tested
      for HIV. Thirty-seven partners (8%) were newly diagnosed with HIV. The number of
      index clients interviewed to identify one partner with newly diagnosed HIV
      infection ranged from 10 to 137 at the participating sites. CONCLUSIONS: PCRS
      provides testing and prevention services to people at high risk for HIV
      infection. Incorporating rapid HIV testing into PCRS and identifying previously
      undiagnosed infections likely confer individual and public health benefits.
      Further evaluation is needed to determine the best methods of identifying
      partners with previously unrecognized HIV infection.

PMID- 19166097
TI  - [The effect of type II diabetes and the metabolic syndrome on cardiac second
      window preconditioning].
AB  - Preconditioning is the most powerful endogenous mechanism, to protect the heart
      against ischemic damage. Conflicting data are published whether preconditioning
      can be induced in case of diabetes and the metabolic syndrome, which are
      clinically very relevant conditions. If preconditioning could be induced
      consistently and chronically in this population, an important reduction of
      surgical morbidity and mortality could be reached. In this project we induced
      hypoxic preconditioning in mice and used cardiac pressure-conductance
      catheterisation and infarct size as outcome parameters. In the first part, we
      found that hypoxic preconditioning was capable to reduce infarct size with 40%
      and preserve the load-independent parameters with 33% after coronary occlusion. A
      DKO (double knock-out: ob/ob; LDLR-/-) model for the metabolic syndrome developed
      a larger infarct size and had a reduced contractility. No preconditioning could
      be induced in this model. To detect the determing factor of the resistance to
      preconditioning, we used single knock-out models. A comparable preconditioning
      effect of wild type mice could be induced in the lipoprotein receptor deficient
      (LDLR-/-) model for dyslipidemia. The leptin deficient (ob/ob) model,
      characterized by insulin resistance and abdominal obesity had, identically to the
      DKO model, a larger infarct size. A second window of preconditioning could be
      induced, although it was less pronounced than the wild type and LDLR-/- model.
      Insulin resistance and abdominal obesity could be identified as the major factor
      in the resistance to preconditioning.

PMID- 19166098
TI  - ABL1 fusions in T-cell acute lymphoblastic leukemia.
AB  - Mutant tyrosine kinases are common in cancer and can be therapeutically targeted
      with kinase inhibitors. To obtain insight in the contribution of activated
      kinases to the pathogenesis ofT-cell acute lymphoblastic leukemia (T-ALL), we
      studied the NUP214-ABL1 fusion gene that is found in 6% of T-ALL and EML1-ABL1
      that we identified in one T-ALL patient. NUP214-ABL1 and EML1-ABL1 display
      constitutive kinase activity and are sensitive to the kinase inhibitor imatinib.
      Both proteins transform hematopoietic cells and we established mouse models of
      EML1-ABL1 and NUP214-ABL1 induced T-ALL. Interestingly, whereas EML1-ABL1
      activity requires homo-oligomerization via its coiled coil domain, activity of
      NUP214-ABL1 depends on its cellular localization to the nuclear pore complexes.
      These results for NUP214-ABL1 delineate a novel mechanism for fusion kinase
      activation in cancer and provide new options to interfere with NUP214-ABL1
      activity. T-ALL development requires accumulation of different mutations. Little
      is known about the cooperation between the mutations and about their sequence of
      accumulation. We provide evidence that tyrosine kinase mutations occur late in T
      ALL development, suggesting limited potential for kinase inhibitor monotherapy.
      We therefore combined NUP214-ABL1 inhibition with other therapies and show that
      inhibition of NUP214-ABL1 and NOTCH1 in vitro can result in synergistic effects.
      Further validation of these and other combination therapies requires animal
      models containing several of the mutations in T-ALL and thus reflecting the
      multistep oncogenic process of human T-ALL genesis. The models for ABL1 fusion
      induced T-ALL will serve as starting point here.

PMID- 19166099
TI  - Implantation of the human embryo: clinical and epidemiological aspects.
AB  - The aim of this thesis is to define determinants of impaired implantation and
      adverse pregnancy outcome in a retrospective manner. Our results demonstrate that
      pregnancy outcome in singletons of older mothers (> or = 35 years) is less
      favourable when compared with younger mothers (25-29 years). Remarkably, the same
      can not be said of twin pregnancies in older mothers. Twins fare better when
      their mother is older than 34 years. In another study, we found higher incidences
      of velamentous cord insertion in twins after assisted reproduction, compared with
      naturally conceived twins. The incidence increased along with invasiveness of the
      applied technique. Since the aetiology of velamentous cord insertion occurs very
      early in the implantation--phase, we hypothesize that increased embryo
      manipulation has an effect on the implantation of the human embryo. Other results
      show that more advantageous pregnancy outcome may be expected when there is
      maximal implantation potential in assisted reproduction. We first hypothesized
      that the more advantageous pregnancy outcome in singletons after single embryo
      transfer (SET) was attributable to a vanishing--twin effect in singletons after
      double embryo transfer (DET). However, our results indicated higher mean hCG-
      values in singletons after SET when compared with singletons after DET. As a
      consequence, we concluded that less good outcomes in singletons after DET are not
      attributable to an early decease of the embryo. Probably only one embryo
      implants, but this implantation may be hampered by the other not--implanting
      embryo.

PMID- 19166100
TI  - [Experimental study of the mechanism for vascular calcification in chronic kidney
      disease].
AB  - Vascular calcification or ectopic calcification ofblood vessels forms an
      important element of the increased cardiovascular risk observed in patients with
      chronic kidney disease. In addition to the classical Framingham risk factors,
      specific uremia-related factors such as hyperphosphatemia and disturbed calcium
      and phosphorus metabolism contribute to the development of vascular
      calcification. To gain a better insight into the mechanism of this calcification
      process, experimental techniques were developed to induce and detect vascular
      calcification in rats with in vivo micro-CT imaging. By means of synchrotron
      based micro-X-ray diffraction the mineral phase deposited in arteries of rats
      with adenine-induced chronic renal failure was found to consist mainly of
      hydroxyapatite, whereas calcifications induced with high dose vitamin D
      administration additionally contained whitlockite, a magnesium-containing
      mineral. Vascular calcification is an active, cell-regulated process. By
      immunohistochemically investigating the expression of bone-specific proteins in
      calciying arteries, we demonstrated that calcifying vascular smooth muscle cells
      are not only able to acquire an osteoblast-like phenotype, but can moreover
      transdifferentiate to chondrocyte-like cells, expressing the cartilage
      transcription factor sox9 and the cartilage extracellular matrix protein collagen
      II. This cartilage phenotype was also found in human aortic tissue. Finally,
      treatment of uremic rats with the calcium-free phosphate binder lanthanum
      carbonate was shown to inhibit the development of vascular calcification,
      implying that adequate phosphorus control without additional calcium load reduces
      vascular calcification. In the future, we will map the proteome of calcifying
      vascular smooth muscle cells and investigate the paradoxical association of
      vascular calcification with impaired bone mineralisation.

PMID- 19166101
TI  - [Dr. Cifuentes centennial].

PMID- 19166102
TI  - [Luis Cifuentes Delatte: a scientist at the service of urology].
AB  - Biographical Sketch of Dr. Luis Cifuentes Delatte (1907-2005), focusing on the
      years of his school and university education, his intense surgical activity
      during Spanish Civil War and his specialized urologic training in Germany and
      U.S.A., as well as his fruitful work in the Hospitals La Princesa and Fundacion
      Jimenez Diaz in Madrid. We cover other extraprofessional features of his life.

PMID- 19166103
TI  - [Urine analysis. Luis Cifuentes in the transition from art to science].
AB  - OBJECTIVE: To emphasize the importance of the study of urine samples as well as
      the non replaceable figure of Dr. Luis Cifuentes Delatte. METHODS: We review the
      methodology of the study of urine samples. RESULTS: Urine analysis keeps a great
      diagnostic importance as Dr. Luis Cifuentes Delatte demonstrated, although it
      unavoidably has suffered modifications due to technological development and
      social needs. CONCLUSIONS: We should never forget in our clinical practice urine
      analysis of the sediment, as Dr. Luis Cifuentes Delatte supported in his time.

PMID- 19166104
TI  - [Notes and brief thoughts about Dr. Luis Cifuentes Delatte (1907-2005)].
AB  - This paper offers a brief biographical sketch of Dr. Luis Cifuentes Delatte (1907
      2005) and his professional and educational activities developed in his late years
      in the Department of Urology at Fundacion Jimenez Diaz (1979-1987), from the
      perspective, the testimony and particular point of view of the author. In
      addition, we emphasize the friendship of Dr. Luis Cifuentes with the philosopher
      Xavier Zubiri (1898-1983) and his cultural links with the intellectual society of
      his time, his origin and personal trajectory from the Ortega's philosophical
      humanist view. In the same way we emphasize Dr. Luis Cifuentes Delatte's
      contribution to the National Academy of Medicine, where he was member (1972
      2005), summarizing his lectures; we also briefly show some of the, unfortunately
      scarce, autobiographical memories the distinguished urologist published.

PMID- 19166105
TI  - [Dr. Luis Cifuentes Delatte in my memory].
AB  - To gloss the figure of Professor Dr. Luis Cifuentes Delatte in both his
      scientific and human features, from the emotional memory of a grateful disciple.

PMID- 19166106
TI  - [Dr. Luis Cifuentes: an exemplary training, scientific and professional
      itinerary].
AB  - We describe the training itinerary of Dr. Luis Cifuentes, in a time in which
      urology lacked scientific prestige and was a limited field of surgery. His
      excellent education in basic sciences, his permanent voluntary contact with the
      most representative scientists of that time, his innovative PhD thesis, and other
      initiatives, altogether with his inquisitorial character and extraordinary
      personal aptitudes enabled him to get to urology with an exceptionally rich
      burden of knowledge. With the help of excellent national and international
      mentors he achieved a urological training of such quality that his scientific and
      professional prestige was immediately recognized, as well as his clinical
      quality, technical expertise, and research rigor. All these led him to leave an
      admirable and everlasting trail. His training itinerary continues being a model
      to be followed by new generations of urologists as a complement to the MIR
      system.

PMID- 19166107
TI  - [The laboratory of the urologist].
AB  - Description of the author' personal relationship with Dr. Luis Cifuentes. We
      emphasize the importance of microscopic evaluation of urine sediment in the
      office of the urologist.

PMID- 19166108
TI  - [Dr. Luis Cifuentes Delatte: clinician, surgeon and researcher].
AB  - The author, disciple of Dr. Cifuentes, thinks about the influence and teaching of
      his professor emphasizing some features that specially marked us. We emphasize
      his capacity to observe reality, his meticulous reading of all tests, his
      analysis of all the information obtained, and his intellectual rigor in the
      elaboration of the diagnosis. His interest for the patient, his thoughts about
      bladder cancer or the importance of statistics, and the introduction and support
      of endoscopic surgery in Spain are outstanding features. It is also outstanding
      his defense of urology as a medical-surgical specialty. As a conclusion we have
      his best legacy: his thoughts, his books and scientific works.

PMID- 19166110
TI  - [Dr. Luis Cifuentes, master and writer].
AB  - In the centenary of Dr. Luis Cifuentes Delatte we tell several histories about
      his teaching, which help to know and understand his professional and human
      quality.

PMID- 19166109
TI  - [To Dr. Luis Cifuentes Delatte: professor, academician, scientific and
      personality of Spanish urology].
AB  - The author describes some of his life experiences with his professor Dr. Luis
      Cifuentes Delatte. We emphasize the scientific, academic and clinical personality
      of professor Cifuentes, one of the most important personalities in Spanish
      urology during the 20th century.

PMID- 19166111
TI  - [Brief life sketch and memories of professor Dr. Luis Cifuentes Delatte, as a
      member of the National Royal Academy of Medicine].
AB  - During my training in the University Clinic of Urology in Munich and Gro-Bhodern
      Hospital I could realize the prestige Dr. Cifuentes Delatte had among my
      professors, who in addition to knowing him personally made frequent references to
      his scientific works. I write in detail the time I met him during my admission in
      the Royal Academy of Medicine as a correspondent academician and the
      conversations we had during the sessions of the Academy, as well as the
      friendship I finally had with him.

PMID- 19166112
TI  - [Dr. Luis Cifuentes Delatte. Memories and teaching].
AB  - OBJECTIVES: With the celebration of the centenary of the birth of Dr. Luis
      Cifuentes Delatte, due to his great scientific personality, we want to emphasize
      two features that, taken from his works and memories, we consider have not been
      emphasized enough: his role as historian of urology, both for the histories he
      narrated of his life experiences and the historical exposition of several
      pathologies, and also his teaching as professor of several generations of
      urologists, with the objective of trying to get to know his great human quality
      as he demonstrated over his life and showed in his writings. METHODS: We review
      his books and works, lectures and published papers, in addition the news about
      his person we have collected from the media, and after analysis, mainly of his
      memories, we extract data reflecting his personality, and they way he thought and
      behaved. RESULTS: Since he was young he went with his father to the international
      urology meetings where he met a great number of personalities in the World of
      Urology; he extended his training with them, and later on they got to have a
      great relationship. He travelled around Europe and United States before and after
      Second World War, respectively, with stays in the most prestigious centers, which
      he described meticulously. He also reported his activity during the first two
      years he directed the Department of Urology at the Hospital La Princesa in Madrid
      and cited the series of collaborators he had. In his research works he made an
      ample description of historical development as introduction to the various
      pathologies he analyzed in depth. CONCLUSIONS: The reading of the narration of
      his trips, that he did in the convulse International time he lived, offers
      details which enable us to know firsthand the situation of urology and the human
      side of the actors he had relation with, and the social life they had, in
      addition to data about their families and daily life. As a researcher in
      transcendental chapters in urological pathology we emphasize his historical
      evolution. A great number of disciples benefited from his scientific quality and
      his great teaching vocation.

PMID- 19166113
TI  - [Dr. Luis Cifuentes Delatte (1907-2005). Biographical sketch].
AB  - OBJECTIVES: With the centenary of the birth of Dr. Luis Cifuentes Delatte,
      considering he in as one of the most transcendental personalities in the Spanish
      urology of the second half of the 20th-century, we review his life, his
      environment, and his relationships, and emphasize his life experiences, in
      addition to his works and research. METHODS: We read his books and articles from
      Spanish urological journals from 1930, from which we selected the references we
      found about him. We also used as a source our personal relationship with him.
      RESULTS/CONCLUSIONS: He had an important clinical and research education, a great
      working capacity; he was a judicious and acute observer, also obiective and
      rigorous checking results; the analysis of urine sediment, urinary tract
      infection with stone formation, and the study of bladder, neurogenic and tumoral
      pathologies, as well as a cystopathies, were the main topics he dedicated to; he
      also was outstanding in transurethral surgery. Valuable publicist, he is
      outstanding due to the transcendence of his written works, and especially for
      being the Master of an ample generation of Spanish and South American urologists,
      and for his love of study and urology.

PMID- 19166114
TI  - [My relationship with Dr. Luis Cifuentes Delatte].
AB  - In this article the author wants to express his admiration and thankfulness to
      his professor in urological endoscopic surgery and show his start in the practice
      of such technique, and the success achieved thanks to the teachings of Dr.
      Cifuentes.

PMID- 19166115
TI  - Congratulatory remarks: Children's Hospital and child health perspectives.

PMID- 19166116
TI  - Myocarditis and complete atrioventricular block: rare, rapid clinical course and
      favorable prognosis?

PMID- 19166117
TI  - Application of array-based comparative genome hybridization in children with
      developmental delay or mental retardation.
AB  - Children with developmental delay or mental retardation (DD/MR) are commonly
      encountered in child neurology clinics, and establishing an etiologic diagnosis
      is a challenge for child neurologists. Among the etiologies, chromosomal
      imbalance is one of the most important causes. However, many of these chromosomal
      imbalances are submicroscopic and cannot be detected by conventional cytogenetic
      methods. Microarray-based comparative genomic hybridization (array CGH) is
      considered to be superior in the investigation of chromosomal deletions or
      duplications in children with DD/MR, and has been demonstrated to improve the
      diagnostic detection rate for these small chromosomal abnormalities. Here, we
      review the recent studies of array CGH in the evaluation of patients with
      idiopathic DD/MR.

PMID- 19166118
TI  - Myocarditis complicated by complete atrioventricular block: nine years'
      experience in a medical center.
AB  - BACKGROUND: Myocarditis complicated with complete atrioventricular block (CAVB)
      is rare in children. The purpose of this study was to report the outcome of
      myocarditis with CAVB in our institution. METHODS: Between June 1998 and June
      2007, nine pediatric patients (aged from 1.5 to 16 years) were admitted,
      presenting with acute myocarditis with CAVB. We analyzed their clinical
      presentations, biochemistry and serology studies, chest X-rays,
      electrocardiograms, echocardiography, complications and outcomes. RESULTS:
      Hypotension and Stokes-Adams seizures occurred in five and four of our patients,
      respectively. Cardiomegaly of chest X-ray was common in eight (89%) of our
      patients. Echocardiography revealed impaired left ventricular performance in
      three patients. Six patients suffered ventricular tachycardia (VT). Three cases
      of VT occurred before pacemaker implantation and the others occurred afterwards.
      Eight patients survived. Six of them regained sinus rhythm within 12 days (range
      1-12 days), and two had a right bundle branch block at follow-up. Two patients
      had persistent CAVB, and one received permanent pacemaker implantation; the other
      received supportive care. One patient died due to persistent low cardiac output
      and a new onset of VT on the 4th admission day. During a follow-up period of 56+/
      27 months, all eight surviving patients remained asymptomatic. CONCLUSIONS: The
      outcome of CAVB complicated with myocarditis is variable. Most of our patients
      resumed normal heart function. The incidence of persistent CAVB was 22%. VT is a
      common and serious complication, but it can be effectively treated medically.
      Persistent low cardiac output after pacemaker implantation and late onset VT
      should be considered as risk factors of mortality.

PMID- 19166119
TI  - Comparison between bubble CPAP and ventilator-derived CPAP in rabbits.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) is used in infants with
      respiratory distress and apnea. Bubble CPAP (B-CPAP) and ventilator-derived CPAP
      (V-CPAP) are two of the most popular CPAP modes, and use different pressure
      sources. However, few studies have been performed to compare their differences
      and effectiveness. This study was to determine whether B-CPAP and V-CPAP would
      have different effects on vital signs and arterial blood gas analysis. METHODS:
      We performed a randomized crossover study to measure vital signs, including mean
      blood pressure (MBP), heart rate (HR), and respiratory rate (RR), in 12 ketamine
      anesthetized healthy rabbits receiving endotracheal intubation by tracheostomy
      with B-CPAP or V-CPAP. Arterial blood was also sampled and analyzed for PaO2,
      PaCO2, HCO3 and pH. RESULTS: We observed statistically significant decreases in
      RR, pH and PaO2 with corresponding incrases in PaCO2 and HCO3 during the V-CPAP;
      however, no significant changes from baseline were observed for B-CPAP. Neither
      modality resulted in statistically significant changes in MBP or HR. Both forms
      of CPAP altered vital signs and arterial blood gases in a similar manner. There
      was a trend towards a lower percentage of change from baseline in all variables
      in B-CPAP compared with V-CPAP. CONCLUSIONS: Our results suggest that B-CPAP
      seems to be superior to V-CPAP in terms of its effect on arterial blood gases and
      vital signs. We speculate that B-CPAP could have certain protective effects that
      better preserve both arterial blood gases and vital signs when compared to V
      CPAP. However, the results of this study still need to be tested by clinical
      study.

PMID- 19166120
TI  - The perinatal outcomes of asymptomatic isolated single umbilical artery in full
      term neonates.
AB  - BACKGROUND: Neonates with a single umbilical artery (SUA) are considered at
      increased risk for chromosomal and structural abnormalities, and an increased
      adverse perinatal outcome. OBJECTIVE: The specific aims of our study were to
      evaluate (1) the association of asymptomatic infants with isolated SUA and
      perinatal outcomes and (2) whether asymptomatic neonates with isolated SUA at
      birth need full investigation. METHODS: The inclusion criteria for the study were
      full-term neonates with isolated SUA delivered from January 1996 to December
      2006. For a control group, we used the next consecutive two newborns delivered
      after the SUA case in the same maternity ward with matched gestational age and
      without phenotypic features suspicious for aneuploidy delivered after each SUA
      group subject. All prenatal, peripartum and delivery records were reviewed for
      maternal demographics, associated anomalies, karyotypic analysis, pregnancy
      complications and perinatal outcomes. All SUA cases had undergone sonogram for
      renal anomalies. RESULTS: We enrolled 14 and 28 cases into the SUA and control
      groups respectively. There was all normal karyotyping for the 14 cases. The
      placental weight in SUA was significantly Lighter compared to that in the control
      group (597.1+/-175.4 vs. 709.3+/-95.2 g, p=0.010). All renal sonographic screens
      and karyotyping in the SUA group were normal. The incidence of small for
      gestational age (SGA) in SUA group was higher compared to control group (SGA,
      5/14, 35.7% vs. 1/28, 3.6%, p=0.011) and less body length (48.7+/-5.0 vs. 50.8+/
      1.8 cm, p=0.028). CONCLUSION: SUA is a relatively rare finding. When a SUA is
      identified, the routine check of karyotyping and kidney sonography for possible
      chromosome and associated renal anomalies may be unnecessary. According to
      lighter placental weight probably causing the higher incidence of small for
      gestational age (SGA), pregnancies with isolated SUA should be carefully
      monitored for evidence of fetal growth restriction.

PMID- 19166121
TI  - A follow-up study of neonatal interatrial shunt with echocardiography until
      twelve to fifteen months of age.
AB  - OBJECTIVES: To assess the incidence and natural history of full-term neonates
      with interatrial shunt (IAS). METHODS: A follow-up study of 1389 neonates who
      received screening echocardiography between 2003 and 2006. Babies with IAS at 2
      to 4 days of life underwent follow-up echocardiography at 2 to 4 months, 6 to 9
      months and 12 to 15 months of age until closure of IAS. RESULTS: The ratio of IAS
      was 68.3% initially. No significant demographic differences were identified
      between infants with and without initial IAS. Among 949 neonates with initial
      IAS, 84.5% infants had a left-to-right interatrial shunt, 13.5% had bidirectional
      shunt and 2% had predominantly right-to-left shunt. The persistence rate of IAS
      at 12 to 15 months of age was 3.8% (44/1166). The initial size of IAS ranged from
      1.2 to 7.7mm (4.3+/-1.1 mm) detected by color Doppler flow mapping and cases were
      divided into three groups: small (< or =5 mm), medium (5 to 8 mm) and large group
      (> or =8 mm). There were 74.6% infants in the small group and 25.4% in the medium
      group initially. The neonates in the initial small group would always see their
      IAS close or else they would remain in the small group. Those in the final medium
      and large size groups always came from the initial medium group. The late closure
      rate of IAS was 93.9% of infants with initial IAS. The closure curves of initial
      small and medium sized groups were significantly different, and their late
      closure rates were 95.1% and 90.4%, respectively. CONCLUSIONS: IAS was very
      common during early neonatal stage, but most cases would close after 1 year. The
      late closure rate of initial IAS was different if using a cutpoint of 5 mm.

PMID- 19166122
TI  - Phenotype and genotype of two Taiwanese cystic fibrosis siblings and a survey of
      delta F508 in East Asians.
AB  - BACKGROUND: Cystic fibrosis (CF) is considered to be a rare disease in Asians. We
      report two cases of CF in a 5-year-old girl and her newborn brother. They are of
      mixed parentage: a Taiwanese mother and an Australian father. METHODS: A
      comprehensive mutational analysis of the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene was completed. Literature was reviewed for
      delta F508 in East Asians. RESULTS: Two mutation sites were identified in the
      siblings. The carrier status of their parents and elder brother were also
      confirmed: heterozygous delta F508 mutation from the father; 13 TG repeats in the
      IVS8-5T from the mother. An update of delta F508 mutation reported in East Asian
      patients from various ethnicities is included; most of them were of mixed
      parentage. CONCLUSION: These two cases are the first report of cystic fibrosis
      associated with a delta F508 mutation in a Taiwanese patient attributable to a
      mutation most commonly seen in Caucasians. We found that the delta F508 mutation
      is of western origin. Asian patients are seldom found with this mutation unless
      they are of mixed parentage. Our findings provide further evidence that different
      ethnicities have their own set of CFTR mutations.

PMID- 19166123
TI  - Non-febrile seizure associated with pericallosal lipoma.
AB  - Intracranial lipoma is a very rare condition, with an incidence of less than 0.1%
      of all intracranial tumors. They are mostly localized in the pericallosal region.
      Pericallosal lipoma is an extremely rare tumor of the central nervous system and
      rarely gives any symptoms. A 6-year-old girl with an unexplained headache was
      admitted to the Pediatric Outpatient Clinic with complaints of non-febrile
      seizure. Her seizure was a complex-partial type. Biochemical tests for seizure
      etiology did not reveal any specific cause. Electroencephalography (EEG) revealed
      typical epileptic activity. Magnetic resonance imaging (MRI) gave images of a
      mass approximately 1 cm in diameter in the vicinity of corpus callosum splenium.
      Her seizures were kept under control with carbamazepine (400 mg/day) and
      indicators of neuromotor development were found to be normal throughout 24-month
      period of follow up. Even though it is a rare condition, pericallosal lipoma
      should also be taken into account in the differential diagnosis of non-febrile
      seizures in children.

PMID- 19166124
TI  - Pneumococcal osteomyelitis: report of one case.
AB  - Acute osteomyelitis is uncommon in pediatric patients, affecting one in five
      thousand children younger than the age of thirteen. Bone infection caused by
      Streptococcus pneumoniae is extremely rare, accounting for only 1.3% of acute
      osteomyelitis in children. We report a case of penicillin-resistant Streptococcus
      pneumoniae-induced acute osteomyelitis in a 7-month-old male infant who was
      treated successfully with intravenous vancomycin and oral clindamycin.

PMID- 19166125
TI  - Plasma copper and ceruloplasmin in patients with alcoholic liver steatosis.
AB  - BACKGROUND: In blood plasma, copper is transported in form of ceruloplasmin.
      Ceruloplasmin is not only a simple transport protein, it is a multifunctional
      protein with other various physiological functions. At least a part of these
      functions is connected with ceruloplasmin's enzymatic activity. AIM OF THE STUDY:
      The effect of alcoholic fatty liver on the metabolism of copper and ceruloplasmin
      was studied. MATERIAL AND METHODS: Patients suffering from alcoholic liver
      steatosis were enrolled in the study. The serum levels of copper,
      apoceruloplasmin and oxidase activity of ceruloplasmin were determined. RESULTS:
      The copper level in patients with liver steatosis was moderately decreased in
      comparison to healthy controls. The difference in apoceruloplasmin levels between
      patients with liver steatosis and healthy controls was not significant, but the
      specific activity of ceruloplasmin in patients was significantly decreased in
      comparison to controls (0.59 vs. 0.82, p<0.001). The decreased specific activity
      of ceruloplasmin in spite of normal levels of apoceruloplasmin in patients with
      alcoholic liver steatosis suggested some problems in copper metabolism in these
      patients. CONCLUSIONS: The results of our study showed disturbances in copper and
      ceruloplasmin metabolism in patients with alcoholic liver steatosis. We can
      conclude that the determination of blood plasma ceruloplasmin level on the basis
      of its enzymatic activity is better than a simple determination of
      apoceruloplasmin (Tab. 2, Ref. 14).

PMID- 19166126
TI  - Haemolytic anaemia and acute liver failure--the initial manifestations of
      Wilson's disease.
AB  - We describe a case of a 16-year-old girl with Wilson disease, which was initially
      presented as Coombs-negative haemolytic anaemia and acute liver failure. The
      diagnosis was based on the findings of low ceruloplasmin serum level and high
      copper levels both in serum and 24-hour urinary excretion. The patient underwent
      orthotopic liver transplantation. A DNA-based diagnostic tool confirmed Wilson's
      disease: the patient was p.H1069Q homozygote. Based on further molecular-genetic
      examinations in the family, Wilson disease was diagnosed seven days later in one
      of the patient's asymptomatic brothers. The proband's cousin was confirmed as a
      carrier of the p.H1069Q mutation (Fig. 1, Ref. 24).

PMID- 19166127
TI  - Recombinant activated factor VII in refractory gastrointestinal haemorrhage of
      unknown aetiology.
AB  - We report a 27-year-old patient who suffered severe gastrointestinal (GI)
      bleeding of unknown aetiology after undergoing elective abdominal surgery to
      remove a colonic tumour. Although the immediate postoperative recovery period was
      uneventful, rectal bleeding and signs of haemorrhagic shock developed within 10
      hours of surgery. Nasogastric aspiration and laparotomy failed to reveal the
      cause of the GI haemorrhage, and the patient remained unresponsive to
      conventional haemostatic therapy. Treatment with a single dose of recombinant
      activated factor VII (rFVIIa) 45 microg/kg led to reduced bleeding, improvements
      in haemodynamic status, and reduced transfusion requirements. Although further
      investigation is warranted, our findings suggest that rFVIla may be useful in the
      rescue treatment of severe GI haemorrhage of unknown origin (Tab. 1, Ref. 17).

PMID- 19166128
TI  - Biomechanical conditions for maintaining body balance in kinesitherapy of
      osteoporotic patients.
AB  - Regularities of mechanical conditions of body's static and dynamic balance are
      applied not only in movement techniques of sports events, but also in setting up
      exercises for osteoporotic patients. It is important to set up exercises in which
      the patient takes such a position where the forces acting upon him (action
      forces) are in balance with the forces generated in the patient's musculoskeletal
      system (reaction forces). On the basis of biomechanical analysis of conditions
      for maintaining a trainee's body balance in training position, we point out the
      importance of individual exercise in sitting and prone positions led by a
      rehabilitation instructor, aiming at the removal of muscular dysbalance, before
      including the patient in group exercise. Following the preparatory exercise, the
      patient gains greater muscular strength and is able to keep balanced positions
      easier while standing. The patient's performance in exercise increases and the
      risk of falling during group exercise diminishes. The aim of the article is to
      motivate rehabilitation instructors to set up an erudite methodology of
      kinesitherapy while meeting the conditions of proportional load of
      musculoskeletal system of osteoporotic patients, based on the principles of
      biomechanics (Tab. 2, Fig. 1, Ref. 10).

PMID- 19166129
TI  - New techniques for assessment of occupational respiratory diseases.
AB  - Recently, as several studies have demonstrated, these non-invasive techniques,
      such as induced sputum (IS) or analysis of the exhaled air; exhaled nitric oxide
      (eNO) or exhaled breath condensate (EBC) provide fairly reliable results that
      correlate with those of "gold standard" methods (bronchoscopy, bronchoalveolar
      lavage) which are more invasive and uncomfortable for patients. Although novel
      approaches have attracted the attention of scientists, they have not been
      examined in relation to occupational settings and professional diseases. The IS
      is a useful biological medium for the diagnosis of occupational asthma and for
      the assessment of exposures to harmful dust at workplaces. The eNO analysis can
      serve as an easy and comfortable diagnostic tool for the professional asthma
      after exposure to various allergens. The examination of EBC biomarkers evaluates
      local doses of hard metals in the lung, as well as detection of oxidative stress
      markers (malondialdehyde, H2O2). Due to the need to standardize the procedures
      for EBC collection, further studies on EBC validation and the subsequent
      application in the clinical and epidemiological fields are required. The
      techniques listed in this article may serve as optimal tools for diagnosis of
      occupational respiratory diseases and for screening/monitoring programs following
      inhalation exposures in future (ref 64).

PMID- 19166130
TI  - Bicarbonate therapy in diabetic ketoacidosis.
AB  - In the treatment of diabetic ketoacidosis (DKA), the aggressive management of
      hyperglycemia, avoidance of hypoglycemia, and anticipation of the diabetic
      systemic complications improve patient outcome. In past, the bicarbonate therapy
      in DKA has been advocated. Yet, no prospective randomized studies on the use of
      bicarbonate in DKA with arterial pH values <6.9 have been published. However, the
      bicarbonate therapy in DKA has several potentially deleterious effects including
      worsening of hypokalemia and intracellular acidosis. Here we present a patient
      with DKA pH<6.9, treated with bicarbonate, who demonstrated a clinical benefit
      (Ref. 11).

PMID- 19166131
TI  - Neurofibroma of the vagus nerve in the cervical portion.
AB  - OBJECTIVE: Neurofibromas of the vagus nerve on the neck are very rare. They are
      asymptomatic, slowly growing. We have seen only one case of neurofibroma of the
      vagus nerve in the mentioned location during last 22 years. CLINICAL
      PRESENTATION: 33-year-old patient with negative family history. She has observed
      increasing swelling on the right side of the neck for about 2 years. She
      complained of the disorders of swallowing, expectoration, aspiration episodes,
      strider, intermittent palpitations, breathlessness, frequent airway infections.
      Magnetic resonance (MR) and angiography (AG) showed expansion in the mentioned
      location. CONCLUSION: We present our experiences with neurosurgical management of
      neurofibroma of the vagus nerve in the cervical portion using microscopic
      technique. We found only 9 described cases of surgical treatment of the
      neurofibroma of the vagus nerve in the neck location in available literature till
      2007 (Fig. 6, Ref. 9).

PMID- 19166132
TI  - An uncontrollable gambling addiction.
AB  - Same authors regard gambling as addiction. A detailed psychiatric examination
      revealed the obsessive-compulsive syndrome in the patient. The authors treated
      the patient systematically using the individual psychotherapy and sertraline from
      low doses up to the maximal dose (i.e., about 200 mg daily). A complete remission
      of the obsessive-compulsive syndrome was achieved. A number of indirect proofs
      demonstrate a significant role of sertraline in the etiology of the obsessive
      compulsive syndrome. The most important evidence is the effectiveness of the
      drugs from the group of selective inhibitors of serotonin central reuptake (SI
      SHT) in the treatment of the obsessive-compulsive syndrome. Sertraline is safe
      and effective in the treatment of obsessive-compulsive syndrome (Ref. 7).

PMID- 19166133
TI  - An anomalous left external jugular vein draining into right subclavian vein.
AB  - Knowledge of the varying drainage patterns of superficial veins of head & neck,
      in particular, jugular veins are not only important for anatomists but also for
      the surgeons operating at this level and to clinicians in general. The variations
      are important also for interventional radiologists, who perform trans-jugular
      procedures, such as port implantations and trans-jugular intra-hepatic porto
      systemic shunts or selective venous samplings. Results of recent studies report
      that the superficial veins, especially the external jugular vein, have been
      increasingly utilized for cannulation to conduct diagnostic and therapeutic
      procedures. We report a very unusual left-sided presentation of external jugular
      vein in an embalmed male cadaver. Embryological evaluations of the anomaly was
      done & compared with available literature, which showed that the observed
      variation is rare (Fig. 1, Ref. 12).

PMID- 19166134
TI  - Vegetarian diets, chronic diseases and longevity.
AB  - Vegetarians form a non-homogenous group consisting of semivegetarians (plant
      food, dairy products, eggs and fish), lacto-ovo vegetarians (plant food, dairy
      products, eggs) and vegans (plant food only). According to pure vegetarian
      ideologists, people consuming vegetarian diet have better health and live longer
      than nonvegetarians, because persons consuming milk, dairy products, meat, eggs
      and fish are at health risk. In fact the most healthy people in Europe are
      inhabitants of Iceland, Switzerland and Scandinavia, consuming great amounts of
      food of animal origin. Meta-analysis of several prospective studies showed no
      significant differences in the mortality caused by colorectal, stomach, lung,
      prostate or breast cancers and stroke between vegetarians and "health-conscious"
      nonvegetarians. In vegetarians, a decrease of ischemic heart disease mortality
      was observed probably due to lower total serum cholesterol levels, lower
      prevalence of obesity and higher consumption of antioxidants. Very probably, an
      ample consumption of fruits and vegetables and not the exclusion of meat make
      vegetarians healthful. Now, the largest cohort study of diet and health on more
      than half million of persons, the European Prospective Investigation into Cancer
      and Nutrition (EPIC) study, will bring new data on the relationships between
      diet, lifestyle and environmental factors and the incidence of cancer,
      cardiovascular and other chronic diseases. Vegetarianism is a form of food
      restriction; and in our overfed society, food restriction is a plus unless it
      results in a nutritional deficiency (Fig. 1, Tab. 2, Ref. 18).

PMID- 19166135
TI  - Laparoscopic pelvic exenteration: a new option in the surgical treatment of
      locally advanced and recurrent cervical carcinoma.
AB  - Pelvic exenteration is an option in the treatment of persistent or recurrent
      cervical carcinomas confined to the central pelvis. The improvement of
      laparoscopic techniques and equipment in combination with broader experience of
      surgeons in laparoscopy made laparoscopic pelvic exenteration possible. This
      article reviews present experience with pelvic exenteration and analyses the
      advantages and disadvantages of the method compared to classical method (Tab. 2,
      Ref. 10).

PMID- 19166136
TI  - Certain aspects of therapy algorithms in acute pancreatitis.

PMID- 19166137
TI  - Glucose transporter type 1 (GLUT-1) deficiency.

PMID- 19166138
TI  - Pesticides and human health.

PMID- 19166139
TI  - [Non-cardiac chest pain and gastroesophageal reflux disease: pathophysiology,
      diagnostic methods and therapeutic approach].
AB  - BACKGROUND: Non cardiac chest pain is a frequent symptom in general population.
      Gastroesophageal reflux disease is the first cause of chest pain without cardiac
      etiology. AIM: This review aimed to determine the specific mechanisms for
      esophageal-induced chest pain, to evaluate the results of the available methods
      of diagnosis, and to precise the therapeutic options in these patients. METHODS:
      Literature Review RESULTS: Gastroesophageal reflux disease is the most frequent
      etiology of "DTPA".The mechanism of pathogeny is complex. After eliminating
      coronary disease, diagnosis is based on esophagus ph-metry and markers.
      Therapeutic test with PPI would be an alternative option to ph-metry. Treatment
      is based on PPI with appropriate dose and duration. Surgical treatment is
      indicated only for selected patients.

PMID- 19166140
TI  - Usefulness of video-capillaroscopy in clinical practice: systematic review of
      indications and results in rheumatology and in non-rheumatic disorders.
AB  - BACKGROUND: Nailfold video-capillaroscopy (VCP) is nowadays worldwide considered
      as one of the best diagnostic noninvasive imaging technique able to study
      microcirculation in vivo. AIM: To review the applications of VCP in the clinical
      practice and its results in rheumatic and non-rheumatic diseases. METHODS: Review
      of literature RESULTS: The possibility of managing the imaging, by means of
      dedicated software able to characterize quantitative and qualitative data,
      represents another relevant property of VCP. This technique is very useful at the
      identification of microvascular involvement in many rheumatic diseases,
      particularly in systemic sclerosis and related disorders. At the same time, VCP
      has been showed valuable in many other extra-rheumatic diseases. The authors
      review the applications of VCP in the clinical practice and its results in
      rheumatic and non-rheumatic diseases.

PMID- 19166141
TI  - [Osteopenia in patients with Crohn disease].
AB  - BACKGROUND: Osteoporosis and osteopenia are frequently reported during chronic
      inflammatory bowel diseases, particularly in Crohn disease (CD). AIM: To
      determine the frequency of osteoporosis and osteopenia of patients with CD and to
      study associated risk factors. METHODS: A forward-looking study was performed
      about 56 cases of CD, 34 men and 22 women, aged 32 + 10.4 years (18-54 years),
      with no other disorders affecting osseous metabolism. A biphotonic X-rays
      absorptiometry densitometry (DEXA) was performed at femoral neck and lumbar
      spine. A multivariate statistical analysis was performed to check for risk
      factors in osseous mineral density. RESULTS: Osteoporosis and osteopenia are
      noticed with respective frequency of 35.7 % and 23.2 %. A statistically
      significant association is found between low osseous density on one hand and
      physical mass index (IMC), localisation on large bowel of the disease and
      corticotherapy on the other hand. The IMC was a risk factor independent from the
      two other factors. Under nutrition, with IMC < 18 kg / m C, was observed at 21
      patients. It was associated to a pathological densitometry in 76.2 % of cases,
      versus 48.6 % in patients having an IMC > 18 kg/m (p = 0.03, Odds ratio = 3.4).
      CONCLUSION: Among risk factors involved in the osteoporosis during CD, the
      nutritional status plays an important role which must be taken into account in
      the treatment of these patients.

PMID- 19166142
TI  - [Management of female dyschezia in primary care consultation: non-instrumental
      biofeedback].
AB  - BACKGROUND: Dyschezia, a frequent pathology, is often self diagnosed and self
      managed by patients and treated indiscriminately by physicians. AIM: Within the
      framework of therapeutic care of dyschezia during primary care consultation could
      the non-instrumental biofeedback applied in urology stand for an alternative?
      METHODS: Prospective study on 17 dyschesic women aged between 20 and 50 who have
      been treated by non-instrumental biofeedback during primary care consultations.
      They have been subject to a detailed anamnesis, a physical test and targeted
      complementary check-ups. A therapeutic protocol (non-instrumental Bio feedback)
      has also been applied to them. RESULTS: 24% of the studied cases have been
      recovered and an improvement has been observed at 35% of them. Positive results
      have been achieved when the disorder was neither ancient (> 3 years) nor severe
      (Score < 4). CONCLUSION: The non-instrumental bio-feedback for dyschezia cases
      should stand for a prior phase to instrumental biofeedback more invasive and by
      far more expensive.

PMID- 19166143
TI  - [Helicobacter pylori infection in childhood revealed by hematemesis: endoscopic
      and pathologic patterns].
AB  - BACKGROUND: Helicobacter pylori infection frequency in hematemesis was scarcely
      studied. AIM: to asses the frequency of this infection in children with upper
      gastrointestinal bleeding and to study the endoscopic and histological features.
      METHODS: It is a retrospective study including 180 children who underwent an
      endoscopy for upper gastrointestinal bleeding. Our population was divided in two
      groups. The group 1 (n=95) has performed gastric biopsy. The group 2 (n=95)
      has'nt performed gastric biopsy. For each group, we studied the personal and
      familial history of gastroenterologic disease, the hospital where they come from,
      the importance of bleeding, the drug intake effecting the gastric mucosa, the
      endoscopic and histological features. RESULTS: The helicobacter pylori infection
      was present in 48% of the children. The mean age of these children was 99.8 +/-
      42.1 months versus 95.7 +/- 44 months (p=0.13) The comparison of the two groups
      according to Hp infection, and the others parameters don't found any differences.
      All the infected children have chronic gastritis 40/40 versus 13/44 in the non
      infected children (p>10 -6). CONCLUSION: The frequency of Hp infection was high
      in this group of patients with upper gastrointestinal bleeding. It was probably
      underestimated because the investigation was not complete. We emphasize that Hp
      infection has to be investigated and systematically eradicated whenever there
      were severe symptoms like hematemesis indicating therefore organic disease.

PMID- 19166144
TI  - Prevalence and risk factors of cesarean section in a population of Tunisian
      diabetic pregnant women.
AB  - AIM: To determine the rate of and indication of cesarean section among women with
      preexisting and gestational diabetes mellitus compared with glucose-tolerant
      women. METHODS: from case-control study of 400 Tunisian pregnant women (200 in
      group diabetes and 200 in group control) seen over a 5-year period for medical
      management, women who had a cesarean section were identified and the reason for
      the section determined from a review of the medical record. A control group of
      women who had a section were obtained from an existing data-base of glucose
      tolerant women. RESULTS: Women in the diabetic group were significantly older,
      with higher BMI and birth weight than in the control group (p<0.05). Total
      cesarean rate was significantly higher in the diabetic group (50,2%) than in the
      control group (28,2%)( OR= 2.72 IC[1.76-4.20]). The rate of elective cesarean
      delivery was significantly higher in the diabetic group (40.5%) than in the
      control group (8.5%) (OR= 4,87 [2,69-8,90]). However, vaginal delivery success
      rate when trial of labour was tried was similar in both study groups (76% and
      78%). Most frequent indications for cesarean delivery in the diabetic group were
      foetal macrosomia and scarred uterus. Multivariate analysis showed that maternal
      obesity, unbalanced diabetes, unplanned pregnancy, and foetal macrosomia were
      significantly correlated with risk of cesarean delivery in diabetic women.
      CONCLUSION: Cesarean rate in our population of diabetic pregnant women is higher
      than in the control group. Maternal obesity, uncontrolled diabetes, unplanned
      pregnancy, and foetal macrosomia were significantly correlated with risk of
      cesarean delivery in diabetic women.

PMID- 19166145
TI  - Efficacy of the Ahmed glaucoma valve implant in eyes with refractory glaucoma.
AB  - BACKGROUND: Implantation of glaucoma drainage devices is currently considered as
      a good alternative to the traditional treatment of refractory glaucoma. AIM: To
      evaluate the efficacy and safety of the Ahmed glaucoma valve implant in eyes with
      refractory glaucoma. METHODS: This retrospective study included 27 eyes from 27
      patients with refractory glaucoma treated with the Ahmed glaucoma valve implant
      between February 1995 and January 2000. We reviewed the final intraocular
      pressure and incidence of complications in all patients. RESULTS: The most common
      aetiology of refractory glaucoma was open-angle glaucoma (48.1%) followed by
      neovascular glaucoma (29.6%). After a mean follow-up of 35.74 months (range 9-52
      months), the mean intraocular pressure decreased from 35.66 mm Hg before surgery
      to 14 mm Hg on the last follow-up visit after surgery. Thus, the procedure was
      successful in 69.23% of cases. Nine patients (33.33%) achieved reduced
      intraocular pressure without additional antiglaucomatous medication. Transient
      postoperative hypotony of < 5 mm Hg occurred in 14.8 % of patients. This was,
      with transient hyphaema, the most common postoperative complication. CONCLUSION:
      The Ahmed glaucoma valve implant seems to be effective and safe for the
      management of refractory glaucoma. However, it is less effective in case of
      neovascular glaucoma.

PMID- 19166146
TI  - [Blood pressure and type 2 diabetes mellitus: impact of the insulin therapy].
AB  - BACKGROUND: The incidence of arterial hypertension is by 2-3 times with diabetics
      than with non-diabetics. Etiopathogenesis of arterial hypertension in type 2
      diabetes is multifactorial insulin-resistance, obesity, hyperlipoproteinemia,
      age, smoking and probably method of treatment (insulin therapy). The aim of this
      retrospective study is to evaluate, over 5 years period, the level of blood
      pressure and the frequency's progression of arterial hypertension in 35 type 2
      diabetes patients treated with insulin METHODS: comparison of 35 type 2 diabetes
      patients treated with insulin to 35 controls treated with oral hypoglycemic
      agents. RESULTS: No significant differences were found over 5 years period in
      mean systolic blood pressure, mean diastolic blood pressure and frequency of
      arterial hypertension. However, frequency of arterial hypertension was correlated
      with mean dose of insulin. CONCLUSION: Our study confirms the long-term results
      found in the literature reading effects of insulin therapy on blood pressure in
      diabetic patients.

PMID- 19166147
TI  - [Influence of consanguinity on clinical characteristics and affective disorders
      frequency in relatives of bipolar I patients].
AB  - BACKGROUND: The genetic transmission of bipolar disorder remained undetermined up
      to now, partly due to clinical and genetically heterogeneity. In Tunisia, genetic
      study will profit from the existence of high rates of consanguinity. AIM: To
      determine the rate of consanguinity in bipolar I disorders sample and to compare
      the clinical characteristics and the frequency of affective disorders in first
      and second degree relatives of probands with and without consanguinity. METHODS:
      One hundred thirty subjects met DSM-IV criteria for a bipolar I disorder were
      recruited. Available Information was obtained from a structured clinical
      interview, collateral history and medical records. The family investigation
      allowed completion of genealogies over three generations. The comparison was
      based on the clinical characteristics (age of onset, numbers of affective
      episodes, nature and severity of the last affective episode) and the frequency of
      affective disorders in first and second degree relatives of probands with and
      without consanguinity. RESULTS: the rate of consanguinity was estimated to 28,5%
      It was higher in patients with family history of affective disorders : 34,2%
      versus 20,4% (p=0,08). Bipolar I patients with consanguinity were characterised
      by a high frequency of affective episodes and a more severe of the last affective
      episode, but theses differences were not significantly. However, the frequency of
      affective disorders was significantly increased in first degree relatives of
      probands with consanguinity: 10,5% versus 6,1% (p=0,01), and in first and second
      degree relatives of probands with consanguinity : 4,5% versus 29% (p=0,02).
      CONCLUSION: The influence of consanguinity on the clinical characteristics and
      the frequency of affective disorders in first and second degree relatives of
      bipolar patients is en favour the recessive polygenetic transmission of bipolar
      disorders.

PMID- 19166148
TI  - [Images in clinical practice. Mesenteric venous infarct].

PMID- 19166149
TI  - Primitive cardiac sarcomas: about 2 cases.
AB  - BACKGROUND: the cardiac sarcomas, although very rare, represent the quasi
      totality of the primitive sly tumors of the heart AIM: it is about a
      retrospective study of two cases of cardiac sarcomas operated in Sahloul
      university hospital of Sousse. CASES: it is about a woman and a man: The
      respective ages were 22 and 45 years. The clinical pattern of the patients was
      polymorphic and the diagnosis put by cardiac echography. Both patients had a
      surgical resection and a chemotherapy. Both patients died in 13 and 18 months
      after the diagnosis. CONCLUSION: because of the extreme rarity of the cardiac
      sarcomas, there is no precise therapeutic strategy. The only consensus concerns
      the surgery as soon as the diagnosis of cardiac tumor is put. The prognosis of
      these tumors is extremely redoubtable with a survival which does not exceed 2
      years after the beginning of the symptomatology.

PMID- 19166150
TI  - [Epithelioid leiomyosarcoma of the uterine cervix: two cases].
AB  - BACKGROUND: The epithelioid leiomyosarcoma of the uterine cervix is a rare tumor.
      Usually, the presenting symptoms are vaginal bleeding and pelvic pain. Surgery is
      the standard treatment. AIM: To present the characteristic of this rare pathology
      by mean of two cases handled in the Institute Salah Azaiz. CASES REPORT: Two
      patients, aged 51 and 42 years, were referred to our institute for vaginal
      bleeding. Tumors were classified stage II proximal and II distal (FIGO
      classification modified by Gustave Roussy Institute). The patients had total
      hysterectomy with pelvic lymph node dissection. Histological exams confirmed the
      diagnosis of epithelioid leiomyosarcoma of the uterine cervix. Adjuvant external
      radiotherapy was performed. At 12 and 36 months, the patients are alive with no
      evidence disease.

PMID- 19166151
TI  - [Uretero-pelvic junction obstruction complicating a crossed renal ectopia].
AB  - AIM: Report a case of a uretero-pelvic junction obstruction complicating a
      crossed renal ectopia. CASE: 49-year-old woman, complained an abdominal mass.
      Radiological investigations concluded to a non functioning right kidney in a
      crossed ectopia. Surgery was decided and the diagnosis of crossed fused renal
      ectopia destroyed on an ureteropelvic junction obstruction was established. This
      kidney was nephrectomised with good outcome.

PMID- 19166152
TI  - Hematocolpos with imperforate hemi-vagina and duplicated uterus: diagnosis and
      treatment.
AB  - OBJECTIVE: To document the means of diagnosis and treatment of the exceptional
      malformation hematocolpos with imperforate hemi-vagina and duplicated uterus
      CASES: Cases of four patients treated at La Marsa University Hospital, in the
      Department of Obstetrics and Gynecology between 2000 and 2004, were reported.
      Mean age=17.2 years (range: 15-22 years). Three left hematocolpos and a right one
      are observed. All patients underwent vaginal conservative surgical treatment
      (excision of vaginal septum) +/- radical treatment: hemi- colpohysterectomy in
      case of failure of conservative treatment. The clinical presentation was a
      primary dysmenorrhea associated with a pelvic collection. An ipsilateral renal
      agenesis is present in all cases. Sonography is essential to assess the diagnosis
      of renal anomalies. Pelvic MRI is the most important examination. It accurately
      localises the different collections and identifies their content. Conservative
      surgical management was effective in three cases out of four.

PMID- 19166153
TI  - [Endo arterial investigation: suspicious for the cholesterol crystal embolism
      disease].
AB  - BACKGROUND: Cholesterol crystal embolism (CCE) is a rare disorder which can
      complicate cardiac catheterization, angiographic studies and cardiovascular
      surgery. The CCE exposes to a great risk of renal failure and it can even
      threaten life by means of a multi visceral failing syndrome. AIM: Report a new
      case of CCE following cardiac catheterization. CASE: We report the observation of
      a 63-year-old patient who had a coronary angiography via the right femoral artery
      after a myocardial infarction. This examination has showed a multi-vessel
      coronary disease. 15 days later, the patient presented purplish and painful
      discoloration of his toes. The laboratory findings showed a mild inflammatory
      syndrome and eosinophilia at 700 / microL. There was not a renal dysfunction nor
      proteinuria nor hematuria. We performed a skin biopsy and made the diagnosis of
      CCE. Trans oesophageal echography objectified an irregular atherosclerotic plaque
      in the isthmic aorta. The CT scan revealed a spindle-shaped aneurysm in the end
      of the abdominal aorta. This aneurysm contains a marginal surrounding thrombosis
      with high embolic risk. The patient was put under clopidogrel, enoxaparin,
      simvastatin, colchicine and atenolol and operated successfully. CONCLUSION: The
      two particularities of this observation are, on one hand, the absence of a renal
      involvement, which represents the main prognostic factor of the CCE. On the other
      hand, the CCE has revealed a very unstable aneurysm of the aorta which could be
      complicated during the cardiac catheterisation. The CCE is a difficult diagnosis
      that must be remembered before any cardiac catheterisation, because it often
      reflects unstable aortic atherosclerotic lesions.

PMID- 19166154
TI  - [Rupture of hydatid cyst of the liver into the duodenum. A case report].
AB  - BACKGROUND: Rupture of hydatid cyst in the digestive tract is a rare complication
      even in endemic areas. AIM: Authors report a case of a hydatid cyst of the left
      hepatic lobe ruptured in the duodenum CASE: was discovered at the occasion of
      epigastric pain and vomiting. Ct-scan revealed presence of air in a calcified
      hydatid cyst of the left liver lobe and a fistulous tract between the cyst and
      the duodenum. Endoscopy confirmed the diagnosis by the visualisation of a
      fistulous orifice of the anterior aspect of the first duodenum with a protrusion
      of hydatid membrane. Patient was treated surgically and had a partial cysto
      pericystectomy and suture of duodenum.

PMID- 19166155
TI  - [Carcinosarcoma of the urinary bladder. Report of three cases].
AB  - BACKGROUND: Carcinosarcoma of the urinary bladder is a very rare neoplasm
      accounting for less than 0,05% of urothelial tumours is a biphasic malignant
      neoplasm with only 79 cases reported in the English literature. Histologically,
      it exhibits morphologic and/or immunohistochemical evidence of epithelial and
      mesenchymal differentiation with the presence or absence of heterologous
      elements. It usually involves aged adults after 60 years and it has a poor
      prognosis. AIM: We report three cases with an emphasis on unusual histologic
      features. CASES: Three male patients age 76 to 86 years were found to have
      polypoid masses in the urinary bladder. In all cases, microscopic examination
      revealed biphasic neoplasms with distinct mesenchymal and epithelial components.
      The two first cases were remarkable respectively by the presence of
      chondrosarcomatous and osteosarcomatous components.

PMID- 19166156
TI  - [Sneddon-Wilkinson's subcorneal dermatosis: an atypical case pustular].
AB  - BACKGROUND: Sneddon-Wilkinson disease (SW) is chronic and benign disease
      belonging to the heterogeneous spectrum of neutrophilic diseases. It is
      characterised by flask, superficial, aseptic pustules, mainly involving the
      trunk, axilla and inguinal folds, favourably responsive to sulfones. AIM: We
      report an original case with an atypical clinical presentation and course. CASE
      REPORT: A 25-year old woman presented with an erythematous pustular eruption that
      had appeared one week before. Similar flare-ups were reported for 3 years. No
      drug intake history nor recent infection were reported. Physical examination
      showed superficial pustules mainly located on the face and limbs, lying on an
      erythematous skin and sometimes grouped in large plaques with a serpiginous
      disposition having a characteristic aspect of hypopyon pustule. A specimen taken
      from the pustules did not show bacterial or fungal infection. Histological
      examination of a biopsy specimen showed subcorneal pustules with a dermal peri
      capillary neutrophilic infiltrate. Direct immuno-fluorescence was negative. No
      associated diseases were found. The patient was resistant to a 1 month treatment
      with dapsone (100 mg/day). Improvement was obtained with acitretin (25 mg/day)
      within 3 months. CONCLUSION: Our case has some specificities: cephalic
      involvement, resistance to dapsone and favourable outcome to a low dose of
      acitretin.

PMID- 19166157
TI  - Shigella and Salmonella serogroups and their antibiotic susceptibility patterns
      in Ethiopia.
AB  - In this study, the serogroup and susceptibility patterns of Shigella and
      Salmonella spp. isolated from stool cultures were determined using standard
      laboratory procedures. Among the 76 Shigella isolates serogroup B (Sh. flexeneri)
      was the most prevalent species (54.0%) and among the 37 Salmonella strains
      serogroup B was also the most prevalent (81.1%). Antibiograms of Shigella and
      Salmonella spp. showed 100% resistance to erythromycin and high resistance rates
      (> or = 75%) to ampicillin, cephalothin, chloramphenicol and tetracycline.
      Salmonella spp. also had high resistance to gentamicin, sulphonamide, and
      trimethoprim-sulfamethoxazole. Shigella were susceptible to gentamicin (100%) and
      nalidixic acid (97.3%) and Shigella and Salmonella were 100.0% susceptible to
      norfloxacin.

PMID- 19166158
TI  - Survey of antibiogram tests in cholera patients in the 2005 epidemic in Hamadan,
      Islamic Republic of Iran.
AB  - An analytical cross-sectional study determined the serogroups and serotypes of
      Vibrio cholerae, and their antibiotic resistance rates, in the 2005 cholera
      epidemic in Hamadan. All 190 patients with positive stool cultures had V.
      cholerae serogroup O1, biotype El Tor and serotype Inaba positive. Of 60 cases
      selected randomly for antibiogram testing, sensitivity to norfloxacin,
      ciprofloxacin, kanamycin, amikacin, tetracycline and doxycycline was 97%, 92%,
      88%, 85%, 77% and 67% respectively. Resistance to furazolidone, trimethoprim
      sulfamethoxazole and erythromycin was 100%, 98% and 62% respectively. Comparison
      with the results of the 1998 epidemic suggests a worrying increase in the
      resistance of V. cholerae to erythromycin, doxycycline and ciprofloxacin.

PMID- 19166159
TI  - [Resistance of Anopheles labranchiae to DDT in Morocco: identification of the
      mechanisms and choice of replacement insecticide].
AB  - A study of Anopheles labranchiae resistance in Morocco was conducted in the
      provinces of Kenitra, Khouribga, Larache, Khemisset and Sale during 2005. An.
      labranchiae was susceptible to propoxur, fenitrothion and permethrin and
      resistant to varying degrees to DDT. Genetically there was no change to the
      target site common to DDT and pyrethroids, the voltage gated sodium channel. The
      resistance seemed to be due to detoxification mechanisms specific to DDT. In
      principle, there should be no obstacle to the substitution of DDT by pyrethroids
      in Morocco. Resistance can then be detected and supervised by more reliable
      molecular tools in the Laboratory of Medical Entomology of the National Institute
      of Hygiene.

PMID- 19166160
TI  - Immigration and hepatitis B virus: epidemiological, clinical and therapeutic
      aspects.
AB  - This study in Italy aimed to evaluate the epidemiological, clinical and
      therapeutic aspects of hepatitis B virus (HBV) infection in a population of
      recent (< 6 months) immigrants. Between February 2003 and December 2004, 83
      (9.3%) out of 890 immigrants tested positive for hepatitis B surface antigen. All
      were men and 62.6% came-from Africa, 21.6% from Asia and 16.8% from Eastern
      Europe. About half (54.3%) of the patients had elevated alanine aminotransferase
      levels and detectable serum HBV DNA. Genotype distribution was as follows: E (20
      cases), D (14 cases) and A (11 cases). Our study underscores the potential of
      migratory flow to introduce genotype non-D hepatitis B virus into our country.

PMID- 19166161
TI  - Seroprevalence of hepatitis B and C infections among young adult males in
      Pakistan.
AB  - This descriptive, cross-sectional study was conducted at 2 military hospitals in
      Pakistan from January 2004 to December 2005. Young adult males with age range 17
      22 years from different districts of Pakistan were screened for hepatitis B
      surface antigens (HBsAg) and anti-hepatitis C antibodies (anti-HCV). Out of 5707
      young men tested, 95 (1.70%) were positive for anti-HCV and 167 (2.93%) for
      HBsAg. Although both viruses were distributed evenly through-for anti-HCV and 167
      (2.93%) for HBsAg. Although both viruses were distributed evenly throughout
      Pakistan, seroprevalence was higher in the provinces of Punjab and Sindh than in
      North-West Frontier province and Baluchistan and Azad Kashmir provinces. Health
      education to the general public, including barbers, would be an important tool
      for control/preventive measures.

PMID- 19166162
TI  - Response to hepatitis B virus vaccination in haemodialysis patients with and
      without hepatitis C infection.
AB  - The aim of this study was to determine the efficacy of hepatitis B virus (HBV)
      vaccination and the response to vaccine in individuals on haemodialysis with and
      without HCV infection. From April 2000 to September 2003 all haemodialysis
      patients referred to the haemodialysis department in a Babol hospital received 4
      microg vaccine intramuscularly at 0, 1, and 6 months. All were negative for HBV
      infection markers (HBcAb, HBsAg and HBsAb). Of 62 patients, 53 (85.5%) responded
      to vaccination and 26 (49.1%) were high responders. All individuals with HCV
      infection responded to vaccination. Duration of haemodialysis had no effect on
      response to vaccination.

PMID- 19166163
TI  - Cost-effectiveness of prescreening versus empirical vaccination for hepatitis A
      in Egyptian children with chronic liver disease.
AB  - The aim of the study was to determine the prevalence of anti-hepatitis A virus
      (anti-HAV) antibodies among 172 children with chronic liver disease, and to
      calculate the cost-effectiveness of prescreening prior to hepatitis A
      vaccination. Anti-HAV antibodies were positive in 85.1%. However, seroprevalence
      of anti-HAV antibodies was 62.1% in children < 5 years and 94.4% in children 5+
      years. We conclude that while it is cost-effective to do prescreening before
      hepatitis A vaccination for children with chronic liver disease aged 5+ years,
      prescreening might not be cost-effective in those aged < 5 years.

PMID- 19166164
TI  - Evaluation of the measles-rubella mass vaccination campaign in the population
      covered by Tehran University of Medical Sciences.
AB  - We evaluated the measles-rubella mass vaccination campaign in the Islamic
      Republic of Iran in December 2003. Vaccination coverage, community awareness of
      the campaign and the quality of vaccination services were assessed in the
      population covered by Tehran University of Medical Sciences. At the end of the
      campaign 96.4% (95% CI: 94.6%-98.2%) of the population sample (n = 390) had been
      vaccinated. Awareness of the campaign was 80.59% of the sample (n = 190) at the
      start, rising to 96.8% during and 100.0% at the end of the campaign. None of the
      24 vaccination teams sampled were over the threshold for unacceptable
      performance. The mass media and vaccination teams demonstrated good performance
      and have achieved their goals.

PMID- 19166165
TI  - Prevalence and predictors of nonfatal myocardial infarction in Jordan.
AB  - This study in May 2002, part of the Jordan Department of Statistics national
      cross-sectional, multistage employment and unemployment survey, measured the
      prevalence of self-reported myocardial infarction (MI) and the association with
      modifiable risk factors among Jordanians aged 40+ years. Of 3083 participants,
      183 (5.9%) had ever been told by a doctor that they had had a MI. The prevalence
      varied by age and sex; 128 (69.9%) of the cases were in men. Among males and
      females, self-reported hypertension and hypercholesterolaemia were significantly
      associated with MI and diabetes was a significant risk factor for women. There
      was a significant relationship between current smoking and MI but not with
      previous smoking. Exercise and body mass index were not statistically significant
      predictors of MI in both males and females.

PMID- 19166166
TI  - Hair lead concentration in the Lebanese population: phase 1 results.
AB  - Phase 1 of this cross-sectional study aimed to compare hair lead concentrations
      and establish the determinants of hair lead levels in 149 occupationally exposed
      individuals versus 177 non-occupationally exposed controls in the Lebanese
      population. In addition to a standardized questionnaire, lead concentration was
      measured by atomic spectrophotometry. A 5-6-fold difference in hair lead
      concentration was found between occupationally exposed and non-exposed
      individuals (23.60 ppm versus 4.33 ppm). Professional exposure, particularly
      working in petrol refining and gasoline stations, had the highest correlation
      with lead exposure. In non-exposed individuals, male sex, non-Lebanese
      nationality and urban worksite correlated with higher hair lead concentration.

PMID- 19166167
TI  - Clinical evaluation of Graves ophthalmopathy in north-east Islamic Republic of
      Iran.
AB  - This study evaluated the prevalence and severity of ophthalmic manifestations in
      all Graves disease patients (n = 68) presenting to endocrine clinics at Mashad
      University of Medical Sciences between December 2002 and September 2005. The mean
      age of patients was 38.0 (SD 14.0) years, range 15 to 71 years. The most common
      complaints were foreign body sensation (54.0%) and puffy eyelids (48.4%). The
      most common apparent abnormality was lid retraction in 64.2% of patients
      (bilateral in 95.3% of cases). The patients had a mean modified Werner's NO SPECS
      classification score of 3.00 (SD 1.46). The score was significantly higher in
      males than females [3.58 (SD 1.44) versus 2.63 (SD 1.35)] and was positively
      correlated with age.

PMID- 19166168
TI  - Retinal examination of diabetic patients: knowledge, attitudes and practices of
      physicians in Oman.
AB  - Knowledge, attitudes and practices of 40 randomly selected physicians was
      assessed in the North Sharqiya region of Oman in 2003. We evaluated non
      ophthalmologist physicians' knowledge of techniques of eye examination of
      diabetic patients, attitudes towards fundus examination and practices of detailed
      eye examination. Knowledge about different parts of the eye was satisfactory in
      only 58% of physicians and knowledge about method of fundus examination for
      diabetic retinopathy was poor in 40%. Attitudes towards eye examination by non
      ophthalmologists at primary level were positive. In practice 20 physicians had
      attempted to use an ophthalmoscope and only 9 could see details of the retina.
      Our general physicians would need detailed training if they are to be involved in
      early detection of diabetic retinopathy.

PMID- 19166169
TI  - Unhealthy lifestyles and ischaemic electrocardiographic abnormalities: the
      Persian Gulf Healthy Heart Study.
AB  - We assessed prevalence of cardiovascular risk factors, ischaemic heart disease
      (IHD) and unhealthy lifestyles in 3723 participants aged > or = 25 years in the
      northern Persian Gulf region; 96.0% had > or = 1 cardiovascular risk factor. Over
      60% had unhealthy body weight, only 8.3% ate the recommended amount of fruits and
      vegetables, 70.6% were physically inactive and 19.0% were current smokers.
      Prevalence of electrocardiogram (ECG) with evidence of IHD was 12.7%. Present or
      past smoking and truncal obesity were independently associated with IHD ECGs in
      men, and past or present smoking and obesity in women. Hypertension and diabetes
      were independently associated with increased risk of IHD ECG.

PMID- 19166170
TI  - An identity-based model for adolescent health in the Islamic Republic of Iran: a
      qualitative study.
AB  - We conducted this study on 52 adolescents from Tehran to investigate their
      perspectives on health. We used the grounded theory approach and the constant
      comparison analysis method. Identity emerged as a core variable along with the
      concepts of friendship and relationships, education, family, lack of limitation
      and community. Identity affects adolescents' health regarding the emerged
      concepts. Participants believed that psychosocial health-related factors were
      more important than physical and individual health factors. Therefore, social
      welfare, healthy family/friendship, and caring for adolescents' individuality are
      important for healthy adolescence.

PMID- 19166171
TI  - Effect of a health promotion course on health promoting behaviours of university
      students.
AB  - The purpose of this pilot study in Turkey was to determine the effects of a
      health promotion course on enhancement of self-care agency and health-promoting
      behaviours of University of Kocaeli students. A group of 41 civil engineering
      students attended a 15-week course developed by the investigator, which included
      30 hours of classroom lectures. The success of the education was measured by pre-
      and post-intervention tests using the Exercise of Self-care Agency scale and the
      Health Promotion Lifestyle Profile II scale. After the course, the self-care
      agency and health-promoting lifestyle scores of the university students increased
      significantly. University students with the lowest scores before the course
      displayed the most progress after the course.

PMID- 19166173
TI  - Smoking habits among university students in Jordan: prevalence and associated
      factors.
AB  - Questionnaires were completed by 712 university students in north Jordan to
      estimate their prevalence of smoking. The reported prevalence of current smoking
      was 35.0% (56.9% for males and 11.4% for females). About 80% were cigarettes
      smokers. The majority (86.3%) of smokers smoked daily. Male sex, higher income,
      lower academic attainment and higher number of friends or family members who
      smoke were associated with increased prevalence of smoking. Those in the faculty
      of religion and law were less likely to smoke compared to those in other
      faculties. The results suggest that policy-makers need to initiate antismoking
      programmes in Jordanian universities.

PMID- 19166172
TI  - Environmental noise in Beirut, smoking and age are combined risk factors for
      hearing impairment.
AB  - Effect of smoking and environmental noise on hearing impairment was investigated
      in 440 people aged 21-50 years living in Beirut. Participants were divided into 4
      groups: nonsmokers and smokers living in noisy areas (70-90 dBA) and non-smokers
      and smokers living in quiet areas (45-55 dBA). Smoking was associated with
      hearing loss at 8000 Hz, in both bivariate and multivariate analysis. An additive
      interaction at high frequencies (mostly at 8000 Hz) between smoking and noise
      appeared after age 40 years. At age 21-39 years, neither smoking nor
      environmental noise had a significant adverse effect on hearing capacity at low
      frequencies.

PMID- 19166174
TI  - Risk behaviours for HIV/AIDS infection among men who have sex with men in Cairo,
      Egypt.
AB  - A sample of 73 men who have sex with men (MSM) in Cairo, Egypt, were screened for
      HIV infection and were interviewed to study their risk behaviours for HIV/AIDS.
      Most (65.8%) had initiated sexual activity before 15 years; 65.8% took both
      active and passive roles in sexual acts. The frequency of sexual acts was < 1 per
      week for 73.3% of those aged 25+ years, but > 1 daily for 25.9% of those aged <
      25 years. Heterosexual relations were reported by 73.3% of the older age group,
      while 70.7% of the younger age group were exclusively MSM. Condoms were always
      used by only 19.2% of the sample.

PMID- 19166175
TI  - Waist circumference and central fatness of Egyptian primary-school children.
AB  - This cross-sectional study of 1283 healthy children (681 boys, 602 girls) aged 6
      11 years tested the degree of correlation between waist circumference
      measurements and adiposity. The children were classified as normal, overweight or
      obese according to their body mass index (BMI). For both sexes a highly positive
      correlation was found between waist circumference and BMI, percentage of body
      fat, subscapular and suprailiac skinfold thicknesses, and the sum of skinfold
      measures. Central overweight and obesity were indicators for central fatness for
      both overweight boys and girls and for obese girls except in age group 6.5 +/- 1
      years. Waist circumference was a good indicator of central fatness (overweight
      and obesity) in children aged 8.5 +/- years and 10.5 +/- 1 years.

PMID- 19166176
TI  - Effects of an awareness symposium on perception of Libyan physicians regarding
      telemedicine.
AB  - The awareness of health care providers, particularly physicians, towards
      telemedicine is pivotal to its development. In this study we distributed
      questionnaires among Libyan physicians attending a medical symposium on
      telemedicine, held in the period 28 February-1 March, 2005. The sample comprised
      28 males and 13 females from different specialties and from different parts of
      the country. Most reported being confused (53.7%) or unaware (14.6%) regarding
      telemedicine before the symposium. Afterwards, 12.2% were confused, 39.0% showed
      excellent understanding and 48.8% reported fair understanding; 97.6% supported
      the implementation of telemedicine in the country and appreciated the importance
      of establishing remote health services.

PMID- 19166177
TI  - Casemix in the Islamic Republic of Iran: current knowledge and attitudes of
      health care staff.
AB  - Casemix is a tool that classifies patients according to their clinical similarity
      and the homogeneity of resources required. A descriptive study was conducted to
      assess the level of knowledge and attitude toward the casemix-based funding
      system among staff working in the Iranian Social Security Organization in Tehran.
      The survey showed that knowledge of casemix and diagnosis-related groups (DRG)
      was poor among the study group and any attempt to implement the casemix system-
      which about three-quarters of high-level staff had never heard of--would be
      likely to fail. This highlights the necessity for creating awareness of the
      casemix and DRG systems among the hospital staff before any action takes place.

PMID- 19166178
TI  - Safety of patient meals in 2 hospitals in Alexandria, Egypt before and after
      training of food handlers.
AB  - We assessed the food safety knowledge and food handling practices of 23 food
      handlers in 2 hospitals in Alexandria, Egypt [Gamal Abdel Nasser (GAN) and
      Medical Research Institute (MRI)] before and after a food safety training
      programme, and also the bacteriological quality of patient meals and kitchen
      equipment. There was a significant improvement in all knowledge-associated
      parameters except for personal hygiene in GAN. There was an improvement in the
      food safety practices in both hospitals. The bacteriological quality of most
      patient meals and food preparation surfaces and utensils improved after training.
      The bacteriological quality of patients' meals served in GAN was generally better
      than that in MRI.

PMID- 19166179
TI  - Assessment of the educational environment at the College of Medicine of King Saud
      University, Riyadh.
AB  - We used an Arabic translation (revised in our college) of the Dundee Ready
      Education Environment Measure (DREEM) inventory to assess the educational
      environment at the College of Medicine in King Saud University, Riyadh. Over 500
      questionnaires were distributed and 222 were analysed. Scores were: 45.0%
      overall; 40.7% for students' perception of learning, 48.2% for perception of
      teachers, 46.3% for academic self-perception, 44.4% for perception of atmosphere,
      and 46.1% for social self-perception. Scores for first year students were
      significantly higher than the others. Scores for pre-clinical students were also
      significantly higher than those of students in clinical years. Sex was not a
      statistically significant variable.

PMID- 19166180
TI  - Serum level of anti-hepatitis B surface antigen 6-8 years after hepatitis B
      vaccination at birth.
AB  - The duration of protection after hepatitis B vaccination in children is unknown.
      We determined the serum level of antibody to hepatitis B surface antigen (anti
      HBsAg) in 273 randomly selected 7-9-year-old schoolchildren from Zanjan City,
      Islamic Republic of Iran, who had been fully vaccinated against hepatitis B
      starting at birth. Titres < or = 10 mlU/mL were considered unprotective. Just
      over half of the children (52%) had titres < or = 10 mlU/mL with no difference
      between the sexes, while 81 (29.7%) had no anti-HBsAg (0 mlU/mL). Three of the
      children had antibodies to hepatitis B core protein. More studies are needed to
      determine the necessity for or timing of booster doses.

PMID- 19166181
TI  - Clinical pattern of nocardiosis in Saudi Arabia: a case series.
AB  - We aimed to study the clinical pattern of nocardiosis in a tertiary care hospital
      in Saudi Arabia using a retrospective review of cases from 1987 to 2003. A total
      of 19 patients were identified as having culture-proven nocardial infection. The
      most common underlying condition was renal transplantation in 8 patients (42%).
      Lungs were the most common sites of involvement in 12 patients (63%). Three
      Nocardia species were isolated in our series: N. asteroides (58%), N.
      brasiliensis (21%), and N. otitidiscaviarum (21%). A high index of suspicion is
      essential in susceptible patients presenting with pulmonary infiltrate, cerebral
      abscess or deep soft-tissue abscess and usually requires an active diagnostic
      workup and early administration of appropriate therapy.

PMID- 19166182
TI  - Massive ovarian oedema: literature review and case presentation.

PMID- 19166183
TI  - Prevalence of glucose-6-phosphate dehydrogenase deficiency among schoolboys in
      Kermanshah, Islamic Republic of Iran.

PMID- 19166184
TI  - [Three-dimensional reconstruction and dynamic analysis of mitral annular based on
      real-time three-dimensional echocardiography images].
AB  - Non-planar saddle-shaped structure of mitral annulus is of significance to the
      diagnosis of mitral regurgitation. Based on real-time three-dimensional
      echocardiography images, a reconstruction and dynamic analysis method of mitral
      annulus was proposed in this paper. First, the boundary points of the mitral
      annulus are extracted by interactive method and are arranged according to their
      positions. Then, based on non-uniform rational b-splines model, the three
      dimensional mitral annulus visualization model is established and the dynamic
      analysis method is developed and programmed. Results show that the reconstruction
      and analysis method proposed in this paper can quickly, efficiently and robustly
      get the motion of mitral annulus.

PMID- 19166185
TI  - [A study on the registration method and precision in image guided surgery].
AB  - Image guided surgery (IGS) means that computers are used for modeling the
      position of patients and providing the surgeons with image guidance for invasive
      procedures. In this paper, we introduce the composition and the work flow of IGS,
      analyze the process and principle of Registration, which is regarded as a process
      to combine the actual position of patients and the visual position of models.
      Seeing that the precision of the registration determines the precision of the IGS
      system directly, we conduct a study on the registration algorithm precision,
      feasibility as well as robustness. Combined with the actual requirements in
      clinical IGS, we also analyze the influence of changes in the number and position
      of markers on registration precision.

PMID- 19166186
TI  - [Dual-source variable pitch spiral CT reconstruction algorithm].
AB  - Computed tomography angiography (CTA) is a useful approach for diagnosing
      vascular diseases. In this paper, we proposed a reconstruction algorithm for dual
      source spiral CT with variable pitch. The projection data are collected by the
      double-source double-multislice spiral CT (DSDMS-CT). However, the pitch of the
      DSDMS-CT is variable other than being constant. We have developed a new formula
      performing interpolation along Z-axis for dual-source spiral CT with variable
      pitch. The dual-source spiral CT with variable pitch can chase contrast bolus
      more flexibly and more effectively. The simulation results show the correctness
      and efficiency of the proposed algorithm.

PMID- 19166187
TI  - [Study of hybrid time-frequency method and characterization of atrial
      fibrillation from surface ECG].
AB  - With the non-invasive analysis of time-frequency features and instantaneous
      frequency (IFs) of atrial fibrillation (AF) from surface ECG signals, some
      important information reflecting the dynamic behavior of atria with AF can be
      extracted. In this paper is proposed a hybrid time-frequency analysis method,
      which uses the respective advantages of Gabor expansion and quadratic Wigner
      distribution. Our study showed that the time-frequency representation of atrial
      fibrillation signals was formulated into the combinations of time-frequency atoms
      series. By controlling the trade-off of resolution and interference terms via
      Manhattan distance threshold, this method in combination with moment-based
      computation obtained more robust estimation of IFs. The comparative analysis of
      10 pairs of non-terminating and terminating types of AF signals suggested that
      hybrid estimation of IFs can detect the reduction of a majority of the
      fibrillatory rate when AF will end. Meanwhile, this method decreases compute
      burden and is a more robust way relative to peak-based or spectrogram method. So,
      the proposed method would have prospective applications in clinical management of
      atrial fibrillation.

PMID- 19166188
TI  - [Rapid-prototyping manufacture of human scoliosis based on laminated object
      technology].
AB  - At present, doctors discuss the situation of scoliosis patients mainly through
      their x-ray photograph. Because of the complexity of human spine structure, it is
      very difficult for doctors to plan & simulate operation or instruct design of
      scoliosis bracket only through the x-ray photograph of patient. In this paper,
      the technology of forming an STL file from CT data was introduced. The solid
      model of a scoliosis patient was reconstructed and transferred to RPM system. A
      human scoliosis model with all spine anatomical structure was manufactured using
      laminated object manufacturing (LOM). It has important clinical value for doctors
      to plan & simulate operation, and it is significant for the development of
      integration of medicine and engineering.

PMID- 19166189
TI  - [MR brain image segmentation based on modified fuzzy C-means clustering using
      fuzzy GIbbs random field].
AB  - A modified algorithm using fuzzy Gibbs random field model and fuzzy c-means (FCM)
      clustering is proposed for segmentation of Magnetic resonance(MR) brain images.
      Spatial constraints using the definitions of homogeneity of cliques and fuzzy
      Gibbs clique potential are introduced in this algorithm. A new modified objective
      function , which is established by introducing the spatial constraints into the
      traditional intensity based FCM algorithm, leads to the establishment of new
      iterative formulas for membership matrix and centroids. This algorithm can
      improve the performance of corresponding traditional one by modifying the
      original intensity based segmentation model. Experiments on synthetic images and
      MR phantoms show the validation of the proposed algorithm, which is usually a
      better alternative for segmenting medical MR images corrupted by noise.

PMID- 19166190
TI  - [Prony analysis method about P-peak detection in ECG].
AB  - The technology of ECG (Electrocardiograph) auto-analysis has developed rapidly in
      recent years. There are lots of related techniques appearing. The majority is
      about R-peak detection. Although P-peak is important too, there are a few kinds
      of method about P-peak detection. In this paper is presented a new method for P
      peak detection. According to Prony analysis, ECG is separated first, and then
      detected. The method gets good result. Data in experiment are from MIT Arrhythmia
      Database. The reliability of this algorithm in accurately detecting the P
      location is 97.8%.

PMID- 19166191
TI  - [Segmentation of medical images based on dyadic wavelet transform and active
      contour model].
AB  - The interference of noise and the weak edge characteristic of symptom information
      on medical images prevent the traditional methods of segmentation from having
      good effects. In this paper is proposed a boundary detection method of focus
      which is based on dyadic wavelet transform and active contour model. In this
      method, the true edge points are detected by dyadic wavelet transform and linked
      by improved fast active contour model algorithm. The result of experiment on MRI
      of brain shows that the method can remove the influence of noise effective and
      detect the contour of brain tumor actually.

PMID- 19166192
TI  - [Study of mass segmentation algorithm for digital mammograms].
AB  - The shape characteristics of breast mass in digital mammograms are important
      clues in discriminating malignant and benign tumors. To provide more valuable
      information from the breast mass for radiologist, an enhanced mass segment method
      is presented. A new region growing with some parameters can be used to segment
      the mass region effectively. Moreover, the feature of the mass edge is well kept.

PMID- 19166193
TI  - [Breathing motion analysis based on cone beam CT images].
AB  - Breathing motion is a rule-based motion. The traditional breathing motion is
      described by mathematical model which can not reflect the different properties of
      different patients or the different breathing periods of the same patient. So, it
      can not satisfy the needs of the real-time and accurate analysis. Accordingly, in
      this paper is proposed a method to establish the breathing model through tracking
      the cone beam CT images which are gained when the patient is breathing freely.
      The model obtained by the proposed method is similar to the traditional model,
      which verifies the feasibility and effectiveness of the proposed method.
      Simultaneously, the proposed method has "real-time" and "accurate" properties,
      which make it valuable in clinical application.

PMID- 19166194
TI  - [Influence of excessive internet use on auditory event-related potential].
AB  - At present, young people's internet addiction has become a serious social problem
      and on important concern in China. Comparison studies of auditory event-related
      potential (ERP) between 9 excessive internet users and 9 common internet users
      were carried out. The obvious influences of excessive internet use on the users
      were observed. The result suggests that excessive internet use may have some
      influences on cerebral cognitive function.

PMID- 19166195
TI  - [A study on the LIS and HIS integration].
AB  - The development of hospital business demands the integration of information
      systems. After studying the relative technologies for system connection,system
      integration and different modes of connecting system, we put forward a protocol
      to integrate the existing laboratory information system( LIS) and hospital
      information system(HIS). It introduces the multi-tier distributed technical
      methods for improving the client/server applications; it ascertains the units and
      transactions participating in workflow integration by referencing the IHE(
      Integrating the Healthcare Enterprises) Laboratory Technology Framework; it
      implements information exchange by Health Level 7(HL7) standards; and it can
      conserve previous investment and avoid some problems of security, maintenance and
      realtime process without the risk of massively updating system.

PMID- 19166196
TI  - [Research on linked list algorithm for fast generation of medical record report].
AB  - A new algorithm to generate the medical record report based on XML and linked
      list is proposed in this paper. It decomposes and abstracts the content of
      report. Reporter can search and reuse the resources quickly, when writing or
      modifying the report. The experiment results prove that the algorithm reduces the
      reporting time and standardizes the content of report.

PMID- 19166197
TI  - [Human cerebral image registration using generalized mutual information].
AB  - Medical image registration is a highlight of actual research on medical image
      processing. Based onsimilarity measure of Shannon entropy, a new generalized
      distance measurement based on Renyi entropy applied to image rigid registration
      is introduced and is called here generalized mutual information (GMI). It is used
      in three dimensional cerebral image registration experiments. The simulation
      results show that generalized distance measurement and Shannon entropy
      measurement apply to different areas; that the registration measure based o n
      generalized distance is a natural extension of mutual information of Shannon
      entropy. The results prove that generalized mutual information uses less time
      than simple mutual information does, and the new similarity measure manifests
      higher degree of consistency between the two cerebral registration images. Also,
      the registration results provide the clinical diagnoses with more important
      references. In conclusion, generalized mutual information has satisfied the
      demands of clinical application to a wide extent.

PMID- 19166198
TI  - [Synchronous playing and acquiring of heart sounds and electrocardiogram based on
      labVIEW].
AB  - In this paper is described a comprehensive system, which can acquire heart sounds
      and electrocardiogram (ECG) in parallel, synchronize the display; and play of
      heart sound and make auscultation and check phonocardiogram to tie in. The
      hardware system with C8051F340 as the core acquires the heart sound and ECG
      synchronously, and then sends them to indicators, respectively. Heart sounds are
      displayed and played simultaneously by controlling the moment of writing to
      indicator and sound output device. In clinical testing, heart sounds can be
      successfully located with ECG and real-time played.

PMID- 19166199
TI  - [Clinical application of 64-slice CT angiography in the evaluation of lumen
      before and after coronary artery stent implantation].
AB  - This is a retrospective study aimed at the clinical application of 64-slice
      computed tomography angiography (CTA) in evaluation the lumen before and after
      coronary artery stent implantation. We collected the coronary artery imaging data
      of 46 patients undergoing 64-slice CT before coronary artery stent implantation
      from July 2006 through May 2007; we also collected the data of 21 patients with
      34 coronary artery stents in the same period to determine the diagnostic accuracy
      of CTA before and after coronary artery stent implantation. The results showed
      that, in 46 patients, 64-slice CT enabled the visualization of the entire
      coronary tree with diagnostic image quality. Sensitivity, specificity, and
      accuracy for the detection of stenosis > or = 50% were 92.11%, 95.64% and 94.97%,
      respectively. In 21 patients with 34 stents implanted, 23 (67.65%) stents showed
      no stenosis, 8 (23.53%) stents showed low degree of restenosis, and 3 (8.83%)
      stents showed high degree of restenosis. In conclusion, we can accurately
      evaluate the degree of stenosis of lumen before and after coronary artery stent
      implantation with the application of 64-slice CTA.

PMID- 19166200
TI  - [Effect of removing turbinate on the airflow distribution in nasal cavity].
AB  - The effect of variation of nasal structure on airflow distribution was
      investigated. Based on the CT images of the nose of a healthy female, a three
      dimensional nasal model was developed. Two new nasal models were produced by
      removing part of inferior turbinate and part of middle turbinate in the left side
      of the original model. The numerical simulation and analysis for airflow field in
      the three nasal models was conducted by the finite element method. The simulation
      results from new models were compared with those from the original model. The
      airflow rate changed in the two sides of new nasal models. The airflow
      distribution and the pressure grades varied in the side of nasal model where part
      of inferior turbinate or part of middle turbinate was removed. The variation of
      nasal cavity structure will result in airflow redistribution in nasal cavity. The
      effect of removing turbinate on the airflow distribution in nasal cavity was
      described quantitatively.

PMID- 19166201
TI  - [Effects of shear stress on expression of plasminogen activator (tPA and uPA) in
      cultured kidney proximal tubular epithelial cells and its significance].
AB  - In this study, we assessed the effects of shear stress on the expression of
      plasminogen activator(tPA and uPA) mRNA in cultured NRK-52E cells (a kidney
      proximal tubular epithelial cell line of normal rat origin) and investigated the
      mechanism of tubulointerstitial extracellular matrix (ECM) remodeling in the
      early stage of diabetic nephropathy (DN). The cultured NRK-52E cells were exposed
      to shear stress of 5 and 10 dyn/cm2 for 1, 3 and 6 hours respectively. Semi
      quantity RT-PCR was used to detect the expression of tPA and uPA mRNA. Shear
      stress down-regulated the expression of tPA and uPA mRNA in cultured NRK-52E
      cells in a magnitude and time-dependent way. The results suggested that the
      increased tubular shear stress in the early-stage of DN could decrease the
      expression of tPA and uPA in renal proximal tubular cells, lead to the reduction
      of tubulointerstitial fibrinolytic activity and involve in the remodeling of ECM.

PMID- 19166202
TI  - [Stresses in portal venous system of pre-hepatic portal hypertension (PHT)
      rabbits].
AB  - Portal hypertension is a common physiopathological change in liver cirrhosis. In
      this study, rabbits were used and the model of pre-hepatic portal hypertension
      (PHT) was induced by partial ligation of portal vein in two steps. We measured
      the diameters of portal vein and small mesenteric vein at different time-points.
      Then we detected the stress forces induced by blood flow in varicose veins and in
      portal vein; such forces included hydrostatic pressure, shear stress and
      circumferential stress. With the increase of the diameter of varicose small
      mesenteric vein, the hydrostatic pressure and circumferential stress gradually
      elevated and shear stress descended markedly in both the portal vein and the
      small mesenteric vein of PHT rabbits, between which there was a positive linear
      correlation. The findings in our study indicate that the complications of PHT are
      partially attributable to the environment of lower shear stress and higher
      circumferential stress in which the blood vessels of portal venous system live.

PMID- 19166203
TI  - [Effects on microstructure and mechanical property of pure titanium (TA1) treated
      by anodic oxidation].
AB  - Effects on surface microstructure and mechanical property of pure titanium (TA1)
      for implant treated by anodic oxidation were investigated. We found that the
      oxide film with a certain uniform and compact color could be achieved by anodic
      oxidation method. However, with the increasing of oxidizing voltage and time, the
      oxide film will be dissolved at local area. The oxygen content of oxide film and
      the hydrogen content of matrix titanium will be raised, and will also be
      increased. In fact, hydrogen could be diffused into matrix titanium. With the
      increase of hydrogen content of matrix titanium and sigmas/sigmab, there appear
      the possible results of plastic deformation and the fracture of implant.

PMID- 19166204
TI  - [Preparation of bovine hemoglobin-loaded nanoparticles used as blood substitutes
      and establishment of reduction system].
AB  - Bovine Hb-loaded nanoparticles with modulated size of pores, for use as blood
      substitutes, were prepared and a nonenzymatic reduction system including two-step
      reduction and process optimization was established to control the metHb level in
      the present study. After the first-step-reduction procedure was performed, the
      raw BHb, being oxidized severely, was encapsulated to form nanoparticles by the
      modified double emulsion method. The binary solvent of dichloromethane (DCM) and
      acetonitrile (Aci) showed properties such as minimizing Hb oxidation and
      enlarging the pores of nanopartilces. Based on the size of pores o f
      nanoparticles evaluated by the diffusion of various substances wi thdifferent
      molecular weights, reducing agents such as ascorbic acid and glutathione present
      in the plasma were selected to perform the second-step-reduction, i. e. to
      further reduce the metHb in nanoparticles. The metHb level was reduced from over
      90% in the raw materials to 1.25% by the two-step-reduction and controlled
      preparation; this is near the level of native blood, possessing the ability of
      carrying/releasing oxygen.

PMID- 19166205
TI  - [Investigations on preparation and release behavior in vitro of 9-nitro
      camptothecin encapsulated micelles].
AB  - 9-nitro camptothecin (9-NC) loaded amphiphilic copolymer micelles were prepared
      with solvent evaporation method. The effects of temperature, distilled water
      volume, stirring rate, and drug input amount on the size and drug content of
      micelles were further discussed. As a result, well dispersed spherical micelles
      with drug content of 4.9 percent and 50 -70 nanometers in diameter were achieved
      with the following preparation conditions: water bath temperature 60 degrees C ,
      distilled water amount 16 ml, stirring rate 6 500 r/min, and drug input amount
      1.2 mg. 9-NC release profiles in vitro illustrated that drug release from
      micelles included initial burst release and following controlled release. The
      release rate was decreased with the increase of drug content.

PMID- 19166206
TI  - [The hydrophilicity and cell affinity of polylactic acid containg bionic function
      group of phosphorylcholine].
AB  - A series of novel biodegradable and bionic functional polymers, PLLA-PC-PLLA,
      were synthesized using L-lactide ring-opening polymerization by L-a
      Glycerophosphorylcholine (PC) from nature source. The hydrophilicity of the
      polymers was investigated. The results made known that, as PC group was brought
      into the backbone of PLLA, PLLA-PC-PLLA gained much better hydrophilicity than
      did PLLA, and polar phosphatidylcholines probably transferred to the sample
      surface in aqueous environment. The relative growth ratios of ECV304 cells to the
      lixivium of all PLLA-PC-PLLA were higher than 84% in 5 d culture. The cells
      adhesion of ECV304 on the films of PLLA-PC-PLLA lagged as compared to that on
      PLLA, but they could proliferate and cover the films in total. The difference
      between PLLA-PC-PLLA and PLLA was due to the existence of PC group. Thus, PLLA-PC
      PLLA, the same as PLLA, are not cytotoxic, and ECV304 can attach and proliferate
      on them. PLLA-PC-PLLA have potential applications in the fields of tissue
      engineering and drug delivery system.

PMID- 19166207
TI  - [Preliminary studies on repairing osteochondral defects in the rabbit knee joint
      by using porous PA66/n-HA combination mesenchymal stem cells].
AB  - We have investigated the effects of repairing knee osteochondral defects in
      rabbit by using porous polyamide 66/nano-Hydroxyapatite (PA66/n-HA) combination
      bone marrow mesenchymal stem cells (MSCs). Eighteen 6-month-old New Zealand
      rabbits were used to produce the models of 4 mm x 4 mm osteochondral defect in
      the middle trochlea groove of femur. These models were randomly divided into 3
      groups: PA66/n-HA + MSCs Group (Group A), PA66/n-HA group (Group B) and Operation
      control-group (Group C) in which operation for osteochondral defects was
      performed but neither material nor cells were implanted. The materials in Group A
      were seeded with MSCs (5 x 10(5)) in vitro before being implanted in to defects.
      The materials in groups A and B were 0.5 - 0.8 mm lower than normal cartilage.
      The animals were killed 1 and 4 months after operation. We assessed the effects
      by means of macroscopic observation, HE staining, toluidine blue staining,
      immunohistochemistry assay for type I and type II collagen. Group A displayed a
      little effect at the 1 month, but at the 4th month, Group A showed better
      results,compared to Groups B and C. At this time point, the repair tissue of
      Group A was regular; it presented more metachromatic substance visualized by
      toluidine blue staining, and it expressed type II collagen(+ +) and type I
      collagen(+). These results demonstrate that the repair tissue in Group A is
      nearly hyaline cartilage. So we presume that porous PA66/n-HA provides
      biomechanical support, and at the same time, MSCs enhance the repair effects.

PMID- 19166208
TI  - [Deposition of hydroxyapatite on the titanium oxide nanotube in simulated body
      fluid].
AB  - High density, well ordered and uniform titanium oxide nanotube arrays were
      fabricated on the surface of titanium substrate by anodic oxidation in 0.5 mol/L
      H3P04 + 0. 138 mol/L NaF solution. Then hydroxyapatite coatings were deposited in
      a simulated body fluid (SBF). The morphology of titanium oxide nanotubes and the
      coatings was observed by means of scanning electron microscope (SEM). The phase
      composition of the coatings was determined by X-ray diffractometer (XRD). The
      phenomenon of polarization was studied by the CHI660A Electrochemical
      Workstation. The titanium oxide nanotube was found to be about 100 nm in
      diameter. The result of the samples soaked in SBF showed that the hydroxyapatite
      coatings were precipitated on the nanotube of titanium oxide.

PMID- 19166209
TI  - [Study on safety and pharmacodynamic action of transdermal liposomal brucine].
AB  - Liposomal Brucine (LB) with high encapsulation efficiency (72%) and small
      particle diameter (mean particle diameter, 54 nm) was prepared by ethanol
      dripping method. The safety and pharmacodynamic action of LB, a new transdermal
      preparation, were investigated in details with the use of white rabbits, guinea
      pigs and mice, respectively. The tests revealed that LB had no acute toxicity to
      integral and broken skin, and had no allergic effects on skin. In writhing test,
      the analgesic effect of LB was higher than that of free brucine. The anti
      inflammatory activity of LB was significantly higher than that of free brucine
      (P<0.01). Meanwhile, LB exhibited a better dose-response manner and a longer
      duration of analgesic effects. In conclusion, LB could reduce the toxicity of
      brucine, enhance the analgesic and antiinflammatory effects of brucine, and
      achieve its sustained-release.

PMID- 19166210
TI  - [Advanced development of blood-gas exchanger].
AB  - In order to simplify the technique of extracorporeal membrane oxygenation (ECMO)
      and apply extracorporeal life support ( ECLS) broadly for assisting the treatment
      of severe respiratory failure patients, we have developed a blood-gas exchanger
      (BGE) with the characteristics of small volume and simple structure. The exchange
      between blood and gas of BGE adopts cross-flowing model; blood flows along the
      outer hollow fiber and gas flows in the inner hollow fiber with the reverse
      direction of blood flowing. The interface of blood flow in and out was designed
      as the internal spiral, and the caliber of BGE is matched with the blood
      interface of dialysis. Thus it may successfully make single-use spiral connectors
      link up mutually in the extracorporeal blood circulation of dialysis, may help
      clinical operations become safe, convenient and easily-controlled, and may
      simplify the technique of EGMO.

PMID- 19166211
TI  - [Factor analysis model for studying the influence of psychological stress on the
      endocrine network of reproduction axis].
AB  - In order to explore the influence of psychological stress on the reproductive
      axis, we started with the original data of biology from animal experiments, then
      we conducted the factor analysis of 6 important bio-regulatory factors and
      established the Factor Analysis Model for the endocrine network of reproduction
      axis under psychological stress. Based on the biological data obtained from
      animal experiments, it is found that, compared with the relationship seen in the
      factor analysis model in normal condition, the relationship among the biological
      factors is more complicated. The key factor, GnRH, has lost its strong regulating
      action on the subordinate factors, especially on E2; on the other hand, beta-EP
      has very strong regulating action on E2, and E2 is controlled mainly by beta-EP.

PMID- 19166212
TI  - [Pressure shift mediated changes of vascular endothelial cell morphology and
      adhesive function in the flow field in vitro].
AB  - In mankind, the circulation system is a closed pressure-loaded system; the
      pressure in circulation flow field would change with the variation of natural or
      pathological geometry of the local bloodvessel, and the pressure shift induced by
      the variation of vascular geometry would lead to a series of physiological and
      pathological changes in the endothelial cells (ECs). This experiment is designed
      to elucidate the effects of different pressure shift on F-actin alignment and
      expression in cultured endothelial cells in vitro, and to investigate the
      relationship between the altered pressure shift and the expression intensity of
      Vascular adhesion molecule (VCAM) and Integrin alphaVbeta3. Non-activated
      cultured ECs and single shear stress loaded ECs as control group were set, the
      double-immuno-fluoro-cytochemistry, laser confocal scanning microscopy and image
      analysis system were used to observe the expression of VCAM, Integrin alphaVbeta3
      and F-actin in endothelial cells which were exposed to levels of pressure shift
      in an improved parallel plate flow chamber. When exposed to different decreased
      pressure shift, the expression intensity of VCAM, Integrin alphaVbeta3 and F
      actin showed regular changes. The decreased pressure shift resulted in changes in
      cell alignment and cytoskeleton F-actin, and also affected ECs adhesion function
      and transmembrane mechanotransduction function which were represented by VCAM and
      Integrin alphaVbeta3 respectively.

PMID- 19166213
TI  - [The neuroprotective role of brain-derived neurotrophic factor for embryonic rat
      cortical neurons against hypoxia via CREB phosphorylation].
AB  - Transcription factor cyclic AMP response element-binding protein (CREB) in
      embryonic cortical neurons is an important modulator of Brain-derived
      neurotrophic factor (BDNF) induced gene expression. Meanwhile, our early
      researches have indicated that BDNF possesses neuroprotective role for hypoxic
      neurons against hypoxia. In order todisclose whether the neuroprotective role of
      BDNF for embryonic rat cortical neurons against hypoxia is fulfilled via
      nucleoprotein CREB phosphorylation, we used western blotting method to detect the
      expression of CREB and phosphorylated CREB in experimental groups (with BDNF) and
      hypoxic control group (without BDNF) with the time changes of exposure to
      hypoxia. Results indicated that hypoxia and BDNF both could induce
      phosphorylation of CREB in embryonic cortical neurons. Phosphorylation of CREB in
      experimental group (with BDNF) was much higher than that in hypoxic control group
      at the same time points (P<0.01). The expression of phosphorylated CREB reached
      the highest level at the first hour after being exposed to hypoxia in
      experimental groups, then phosphorylated CREB decreased slowly and remained at
      the level for much longer time in experimental groups than in control group. The
      total amount of CREB in embryonic cortical neurons at the first 0-3 hours after
      being exposed to hypoxia in experimental groups were the same as that in hypoxic
      control group. CREB decreased more quickly in hypoxic control group at 5-6 hours
      after hypoxia. This in vitro research demonstrates that BDNF plays its
      neuroprotective role for embryonic rat cortical neurons against hypoxia via CREB
      phosphorylation.

PMID- 19166214
TI  - [Construction and identification of recombinant firefly luciferase report vector
      containing human acyl coenzyme a: cholesterol acyltransferase 1 gene P7
      promoter].
AB  - The DNA segment of the human acyl coenzyme A: cholesterol acyltransferasel
      (ACAT1) gene P7 promoter was amplified by PCR from human monocytic leukemia cell
      line (THP-1) and cloned to TA vector, then the positive clone was confirmed by
      restriction enzymes and sequencing. The targeted segment was subcloned to Firefly
      luciferase report vector pGL3-Enhancer. The recombinant plasmid pGL3E-P7 was
      transfected transiently into THP-1, then the expression of luciferase could be
      detected in THP-1 by pGL3E-P7 transfection. We successfully constructed
      luciferase reporter vector containing P7 promoter of the human ACAT1 gene, and
      established a new means to study the transcriptional regulation mechanisms of
      ACAT1 during atherosclerosis.

PMID- 19166215
TI  - [Differentiation of human umbilical cord blood-derived mesenchymal stem cells
      into chondroblast and osteoblasts].
AB  - Samples of healthy and full-term human umbilical cord blood samples were obtained
      asceptically. Mesenchymal stem cells (MSCs) were isolated by lymphocyte
      separation medium, and were characterized morphologically by fluorescence
      activated cell sorting analysis. Differentiation of chondroblast and osteoblast
      was induced by 10 ng/ml TGF-beta, 100 ng/ml insulin and 10(-7) mol/L decaesadril,
      6.25 microg/ml siderophilin, 10 mmol/L beta-sodium glycerophosphate, 50 microg/ml
      antiscorbic acid, respectirely; the aim was to investigate the potentiality of
      differentiation. Umbilical cord blood-derived MSCs were stained positive for MSCs
      marker CD13, CD90, CD166, CD73, CD44 and HLA-AB, but were negative for
      hematopoietic stem cell marker CD45, CD34 and HLA-DR. After 21 days induction,
      Toluidine Blue staining and von-Kossa staining were positive. Immunocytochemistry
      showed that Collagen II expressed in the induced cells. The results demonstrated
      that mesenchymal stem cells can be isolated from human umbilical cord blood and
      differentiated into chondroblasts and osteoblasts in vitro.

PMID- 19166216
TI  - [HeLa apoptosis induced by co-immobilized cytokines].
AB  - IFN-gamma and TNF-alpha were co-coupled to the polystyrene cell culture plate by
      the photo-immobilization method. To investigate the synergistic effect of IFN
      gamma and TNF-alpha on the HeLa cells, HeLa cells were treated with co-coupled
      cytokine or non-coupled cytokine in a time course in this study. The morphology
      detection, cell cycle analysis by flow cytometry, phosphatidyl serine analysis
      and capase-3 activity detection demonstrated that the two kinds of treatments
      both induce HeLa cells apoptosis. Non-coupled cytokine worked more quickly while
      co-coupled cytokine kept more permanent effect. The caspase-3 activity assay
      indicated that the caspase-3 activity of HeLa cells treated with non-coupled
      cytokine is higher than that of HeLa cells treated with co-coupled cytokine. This
      may imply that co-coupled cytokine not only induces the caspase-dependent
      pathway, but also induces the caspase-independent pathway.

PMID- 19166217
TI  - [Prediction of the B cell epitopes for the major outer membrane protein of
      Chlamydia trachomatis].
AB  - To predict the B cell epitopes for major outer membrane protein (MOMP) of
      Chlamydia trachomatis (CT), the secondary structure of CT MOMP was predicted by
      the methods of GOR based on the sequence of amino acids of E serotype CT MOMP. By
      combining the comprehensive analysis of transmembrane domain, hydrophilicity
      profile, surface probability, antigenic index and average flexibility, the B cell
      predominant epitopes of CT MOMP were further predicted. The N-terminal No. 73-81,
      217-225, 377-386, 261-270 and 161-175 were the predominant B cell epitopes.
      Prediction of the B cell epitopes for the CT MOMP by the multi-parameters is
      helpful for the identification of B cell epitopes.

PMID- 19166218
TI  - [Prokaryotic expression and purification of different truncated protein of
      Mayven].
AB  - To understand the function of Mayven and investigate the pathogenesis of multiple
      sclerosis, the gene sequences of different truncated Mayven were amplified from
      the gene library of human brain. These truncated fragments, including fragment P1
      (1-902 bp), fragment P2 (1-523 bp), fragment P3 (507-182 bp) and fragment P4 (887
      1782 bp), were cloned into pGEX-4T-2 vector to construct recombinant plasmids.
      The recombinant plasmids were transformed into E. coli BL21(DE3) and induced to
      express by IPTG. The expressed proteins were detected by SDS-PAGE and Western
      blot, and were purified by GST purifying system. The results showed that
      recombinant express vectors of different truncated GST-Mayven were successfully
      constructed and were expressed in soluble form protein induced by IPTG. The
      fusion proteins have good reactivity to GST antibody. The construction of
      recombinant express vectors of different truncated GST-Mayven lays a basis for
      further function study on Mayven.

PMID- 19166219
TI  - [Establishing an organic model of SMC proliferation with cultured aorta of rats
      and exploring the underlying mechanism].
AB  - To study the mechanism of proliferous vascular disease as well as its prevention
      and treatment, an organic model was established with cultured aortas of rats, and
      the mechanism there-in invloved was probed. Immunostaining histology showed that
      smooth muscle cell (SMC) proliferation was observed in the aorta segments of
      rats, after their endothelia being injured and cultured in vitro with 20% fetal
      bovine serum. After being cultured for 5 days, various degrees of proliferation
      of SMC on cultured artery segments were observed by HE staining, and conspicuous
      plaques were developed after being cultured for 13 days. The proliferous SMC was
      also observed by Brdu labeling. RT-PCR examination showed that the mRNA
      expression of hypertension-related gene-1 (Hrg-1) and smooth muscle 22 alpha
      (SM22a) in the aortas decreased with the prolongation of culture time, and
      completely disappeared after being cultured for 13 days . But when cultured in
      vitro for ten days, the ET-1 content of supernatant and the proliferous SMC
      labeled by Brdu increased obviously and the expressions of Hrg-1 and SM22a
      decreased after the endothelium was destroyed. Compared with the injured
      endothelium groups, the proliferous SMC of injured endothelium plus BQ123 groups
      decreased visibly. The same significant differences between serum groups and
      serum-free groups were also observed. These results suggest that the culturing of
      rat aorta segments in vitro can induce the proliferation of SMC and the transform
      of phenotype from contractile type to synthetic type. The ET-1 and serum are the
      main factors in the proliferation of SMC and in the transform of phenotype. This
      organic model could serve as a good experimental platform for the researches into
      the mechanism of proliferous vascular disease as well as its prevention and
      treatment.

PMID- 19166220
TI  - [COX-2 or nNOS mediates cardioprotection during the final stage of the late phase
      of ischemic preconditioning].
AB  - The aim of the present studies was to investigate the cardioprotection of late IP
      at 72 h and determine the involvement of iNOS, nNOS and COX-2 in this protection.
      Conscious rabbits were preconditioned with three cycles of 5-minute coronary
      occlusion/5-minute reperfusion. The myocardial infarct area in the rabbits
      preconditioned 72 h earlier was significantly smaller than that in control
      rabbits. The activity of lactate dehydrogenase (LDH) and the level of 6-Keto
      PGF1alpha in the rabbits preconditioned 72 h earlier were lower than those in
      control rabbits. The left ventricular systolic pressure (LVSP) and maximal
      velocity of contraction and relaxation (+/- dP/dtmax) were improved in rabbits
      preconditioned 72 h earlier. The nNOS-selective inhibitors N-propyl-L-arginine
      and selective cyclooxygenase-2 (COX-2) inhibitor celecoxib completely blocked the
      protection of late IP at 72 h, whereas the iNOS selective inhibitor S
      methybisothiourea had no effect. In conclusion, the cardioprotection observed in
      the final stage of late IP (72 hours) is mediated by nNOS or COX-2, but not by
      iNOS.

PMID- 19166221
TI  - [A study on surface plasmon resonance-based gene chip].
AB  - The surface plasmon resonance (SPR)-based gene chip was prepared according to the
      following processes: First, a film of nanogold, which was synthesized by using
      Frens' method, was plated on chip by Chlorauric acid/hydroxylamine method. Then
      probes were fixed on nanogold film by Self-assembled monolayer (SAM) technology.
      Subsequently, the fixing time and concentration of probes, the sensitivity and
      the specificity of the chip were optimized. Our results suggested that the chip
      plated with 2.5 nm nanogold film has a better SPR reflection, and when fixed by
      probes for 4.5 h at the concentration of 1 500 nmol/L, the gene chip also shows a
      fine performance of detection and can identify accurately the mismatch between
      bases in SPR detection system. The gene chip constructed in the research can be
      used for SPR sensor detection.

PMID- 19166222
TI  - [Microstrip antenna design and system research of radio frequency identification
      temperature sensor].
AB  - Radio frequency identification sensor network, which is a product of integrating
      radio frequency identification (RFID) with wireless sensor network (WSN), is
      introduced in this paper. The principle of radio frequency identification sensor
      is analyzed, and the importance of the antenna is emphasized. Then three kinds of
      common antennae, namely coil antenna, dipole antenna and microstrip antenna, are
      discussed. Subsequently, according to requirement, we have designed a microstrip
      antenna in a wireless temperature-monitoring and controlling system. The
      measurement of factual effect showed the requirement was fulfilled.

PMID- 19166223
TI  - [The improved FOCUSS combined with the fMRI priors for EEG source localization
      and its preliminary application].
AB  - The sources generating the scalp recordings can be more precisely estimated with
      the use of fMRI priors. In this paper, an improved source localization algorithm
      which combines the fMRI priors into the iteration procedure of FOCUSS is
      presented. The modified algorithm consists of three steps: Firstly, the
      statistical parameters of fMRI are estimated with the ruler of SPM; Secondly, a
      diagonal weight matrix is constructed with the estimated parameters; Finally, the
      weight matrix is integrated into the iteration procedure of FOCUSS. The method
      was used to localize the EEG sources in the form discrimination experiments,
      where the fMRI and EEG were recorded, and the results preliminarily confirmed the
      validity of method.

PMID- 19166224
TI  - [Suppression of geomagnetic field interference in the magnet locating system of
      the micro-magnetic capsule inside the alimentary tract].
AB  - A method for the suppression of geomagnetic field interference is here-in
      introduced. It is designed for use in the magnet locating system of the
      engineering-based microcapsule inside the alimentary tract. This method marks the
      geomagnetic field interference levels by getting the static value. Then
      subtracting the static value from the dynamic value. The results of the
      experiment show that the method can assess the geomagnetic fi eld interference
      levels around thelocating waistcoat accurately. And the three-dimensional
      tracking trajectory shows that the method has greatly improved the accuracy of
      the capsule location inside the alimentary tract.

PMID- 19166225
TI  - [Experimental research for position accuracy of caput femoris center in total
      knee replacement navigation surgery].
AB  - Finding the position of caput femoris center by exact and fast method is a key
      technique in total knee replacement navigation surgery. A method for finding the
      position of caput femoris center is described in this paper. The main idea is
      abstracting this problem to a geometrical model in which the center of a sphere
      can be easily worked out with a few known spherical points. Experiments show that
      the method is feasible and the precision satisfies the requirements of navigation
      surgery.

PMID- 19166226
TI  - [Fractal research of neurite growth in immunofluorescent images].
AB  - Fractal dimension has been widely used in medical images processing and analysis.
      The neurite growth of cultured dorsal root ganglion (DRG) was detected by
      fluorescent immunocytochemistry treated with nerve regeneration factor (0.1, 0.5,
      2.0 mg/L). A novel method based on triangular prism surface area (TPSA) was
      introduced and adopted to calculate the fractal dimension of the two-dimensional
      immunofluorescent images. Experimental results demonstrate that this method is
      easy to understand and convenient to operate, and the quantititve results are
      concordant with the observational findings under microscope. This method can be
      guidelines for analyzing and deciding experimental results.

PMID- 19166227
TI  - [Artificial muscle and its prospect in application for direct cardiac compression
      assist].
AB  - Artificial heart is an effective device in solving insufficient native heart
      supply for heart transplant, and the research and application of novel actuators
      play an important role in the development of artificial heart. In this paper,
      artificial muscle is introduced as the actuators of direct cardiac compression
      assist, and some of its parameters are compared with those of native heart
      muscle. The open problems are also discussed.

PMID- 19166228
TI  - [Progess on research of herpes simplex virus type 1 mutants for cancer therapy].
AB  - For a long time past viruses have been recognized as being tumoricidal. At
      present, researchers are still pursuing studies and constructing more suitable
      oncolytic viruses for treating different malignant tumors. Herpes simplex virus
      type 1 (HSV-1) has been known as the most potential oncolytic virus among all the
      viruses. In this overview, we summarize the current situation of oncolytic
      viruses, the biology of HSV-1, its construction and application of its
      recombinant, and we debate on the feasibility and prospect of HSV-1 mutants
      labeled with radionuclides for cancer therapy.

PMID- 19166229
TI  - [Current studies and prospective strategies in tissue-engineered trachea].
AB  - Over the past 10 years, much progress in the development of tracheal substitute
      by using tissue engineering techniques has been made. Nevertheless, some issues
      such as optimal extracellular matrix, cell culturing and seeding, epithelial
      regeneration, and revascularization remain the most stimulating challenges in
      tissue engineering science. It is stated that new study strategies and approaches
      should be explored to tackle these key problems in the near future. Here we
      present a review in the attempts to summarize the current advances in tissue
      engineered trachea, and to look forward the prospects.

PMID- 19166230
TI  - [Application of elastin in biomedical materials].
AB  - Elastin is a natural biomedical material of great potential. Being endowed with
      the special crosslinking and hydrophobic structure, elastin retains many good
      properties such as good elasticity, ductibility, biocompatibility,
      biodegradability and so on. Nowadays, elastin as a material, which is gradually
      attracting people' s attention in the biomedical materials field, has been used
      as tissue engineering scaffolds, derma substitutes and other biomedical
      materials. In this context, a systematic review on the characteristics of elastin
      as a biomedical material and on the actuality of its application is presented.
      Future developments of elastin in the field of biomedical applications are also
      discussed.

PMID- 19166231
TI  - [Research progress of joint kinematics and kinetics].
AB  - The development process of joint kinematics and kinetics is expatiated from the
      aspects of technology and method. Firstly, the classical mechanics-based methods
      are introduced. Secondly, the computer assisted methods are analyzed from the
      technical aspects of video tracking, fluoroscopy and MR imaging separately. Then
      the assistance of robotic technique in this field is discussed. Finally the
      potential trend in the joint kinematics and kinetics is concluded.

PMID- 19166232
TI  - [Effects of Rho proteins on the cytoskeleton activity and the growth regulation
      in tumor cells].
AB  - The researches on Rho family proteins have been progressing very fast recently.
      Rho proteins mainly regulate the reorganization of actin cytoskeleton, thus
      controlling the cell morphologic changes and the motility. There is a close
      relationship between Rho proteins and tumors; under the function of regulators
      and effectors, the activation of Rho proteins can enhance cell motility, induce
      gene expression in cell cycle progression, and promote the degradation and re
      establishment of extracellular matrix. Accordingly, Rho proteins play a crucial
      role in regulating tumor cells' proliferation, apoptosis, invasion, metastasis
      and other biological behaviors. Further researches on Rho proteins can help to
      clarify the mechanism involved in these effects, thus providing a potential
      evidence in anti-tumor therapy.

PMID- 19166233
TI  - [The role of electronic techniques for advanced neuroelectrophysiology].
AB  - The rapid development in the fields of electroscience, computer science, and
      biomedical engineering are propelling the electrophysiologyical techniques.
      Recent technological advances have made it possible to simultaneously record the
      activity of large numbers of neurons in awake and behaving animals using
      implanted extracellular electrodes. Several laboratories use chronically
      implanted electrode arrays in freely moving animals because they allow stable
      recordings of discriminated single neurons and/or field potentials from up to
      hundreds of electrodes over long time periods. In this review, we focus on the
      new technologies for neuroelectrophysiology.

PMID- 19166234
TI  - [Advances and trends in the researches on meridians].
AB  - This review summarizes the newest advances in recent researches on meridian.
      Firstly, fascia, connective tissue, mast cells, fibroglia fibrils and
      interstitial fluid are found accumulated under the deeper layer tissue of the
      acupoints and channels, thus giving indications of their important role in the
      propagated sensation along meridian. Secondly, the supplementary data involve the
      characteristics and the neurobiological basis of propagated sensation along
      meridian, which suggest that the function of the meridian is of integrity, i.e.
      the points on different segments of the same channel produce a uniform clinical
      effect. The effect of Luomai (collateral, branch of the large channel) and the
      mechanism of long distance of transmission across spinal segments are introduced.
      Thirdly, the objective evidence of channel-viscera bi-directional correlativity.
      Lastly, the application of the gene chip technique to meridian research. As for
      the main trends in the researches of meridian, the emphases are laid on the
      function of acupoints and channels, on the correlation between the channel and
      internal organs, on the rational distribution of proportion as well as on the
      coordination of meridian research between laboratory experiments and clinical
      practices. Recently, faced to international competition, Chinese physicians and
      researchers feel an unshrinkable duty and are making a greater effort to carry
      out researches on the meridian.

PMID- 19166235
TI  - [The progress of research on low-frequency sonophoresis and its applications].
AB  - Low-frequency ultrasound can increase the transdermal delivery of many drugs,
      including macromolecular drugs. The main mechanism is ultrasonic cavitation. Most
      researchers pointed out that it could change the form-structure of stratum
      corneum keratinocytes and, in this way, it can improve the permeability of skin.
      Low-frequency sonophoresis has been in use for in-vitro experiments and in-vivo
      animal experiments, and so far, both small-molecules transdermal delivery and
      macromolecules transdermal delivery have been successfully performed in many
      experiments. However, there are few reports about the real low-frequency
      sonophoresis for clinical treatment. A large number of clinical trials are
      necessary to confirm its safety and practicality. Once its safety is confirmed
      and the suitable low-frequency sonophoresis devices are developed successfully,
      Low-frequency Sonophoresis will come to be a safe, effective, controllable, and
      economic new delivery method.

PMID- 19166236
TI  - Clinical, technical, and basic science progress in helical tomotherapy--the pace
      continues to accelerate.

PMID- 19166237
TI  - Comparison of the helical tomotherapy and MLC-based IMRT radiation modalities in
      treating brain and cranio-spinal tumors.
AB  - The investigation of the clinical efficacy and effectiveness of Intensity
      Modulated Radiotherapy (IMRT) using Multileaf Collimators (MLC) and Helical
      Tomotherapy (HT) has been an issue of increasing interest over the past few
      years. In order to assess the suitability of a treatment plan, dosimetric
      criteria such as dose-volume histograms (DVH), maximum, minimum, mean, and
      standard deviation of the dose distribution are typically used. Nevertheless, the
      radiobiological parameters of the different tumors and normal tissues are often
      not taken into account. The use of the biologically effective uniform dose (D=)
      together with the complication-free tumor control probability (P(+)) were applied
      to evaluate the two radiation modalities. Two different clinical cases of brain
      and cranio-spinal axis cancers have been investigated by developing a linac MLC
      based step-and-shoot IMRT plan and a Helical Tomotherapy plan. The treatment
      plans of the MLC-based IMRT were developed on the Philips treatment planning
      station using the Pinnacle 7.6 software release while the dedicated Tomotherapy
      treatment planning station was used for the HT plan. With the use of the P(+)
      index and the D(=) concept as the common prescription point, the different
      treatment plans were compared based on radiobiological measures. The tissue
      response probabilities were plotted against D(=) for a range of prescription
      doses. The applied plan evaluation method shows that in the brain cancer, the HT
      treatment gives slightly better results than the MLC-based IMRT in terms of
      optimum expected clinical outcome (P(+) of 66.1% and 63.5% for a D(=) to the PTV
      of 63.0 Gy and 62.0 Gy, respectively). In the cranio-spinal axis cancer, the HT
      plan is significantly better compared to the MLC-based IMRT plan over the
      clinically useful dose prescription range (P(+) of 84.1% and 28.3% for a D(=) to
      the PTV of 50.6 Gy and 44.0 Gy, respectively). If a higher than 5% risk for
      complications could be allowed, the complication-free tumor control could be
      increased by almost 30% compared to the initial dose prescription. In comparison
      to MLC based-IMRT, HT can better encompass the often large PTV while minimizing
      the volume of the OARs receiving high dose. A radiobiological treatment plan
      evaluation can provide a closer association of the delivered treatment with the
      clinical outcome by taking into account the dose-response relations of the
      irradiated tumors and normal tissues. The use of P - (D=) diagrams can complement
      the traditional tools of evaluation such as DVHs, in order to compare and
      effectively evaluate different treatment plans.

PMID- 19166238
TI  - Planning and delivery of whole brain radiation therapy with simultaneous
      integrated boost to brain metastases and synchronous limited-field thoracic
      radiotherapy using helical tomotherapy: a preliminary experience.
AB  - Lung cancer is the commonest source of brain metastases, which has been
      traditionally treated with Whole Brain Radiation Therapy (WBRT) with or without
      focal boost. We herein report our preliminary experience of the planning and
      delivery of WBRT with Simultaneous Integrated Boost (SIB) to brain metastases
      along with synchronous limited-field thoracic radiotherapy using Helical
      TomoTherapy in four patients with lung cancer. All plans were iteratively
      optimized for maximal target volume coverage and organ-at-risk (OAR) sparing.
      Standardized dose metrics were used for plan evaluation. All treated regions were
      imaged with a megavoltage computed tomography (CT) prior to treatment and co
      registered with planning CT for image-guidance. Helical TomoTherapy was able to
      achieve highly conformal and homogeneous dose distributions with excellent OAR
      sparing both in the brain and the chest. The mean (standard deviation) Dose
      Homogeneity Index (DHI) and Conformity Index (CI) was 0.06 (0.01) & 0.79 (0.07);
      0.04 (0.02) & 0.57 (0.22); and 0.03 (0.02) & 0.77 (0.06) for whole brain, brain
      metastases, and chest, respectively. The mean monitor units (MU) per fraction and
      time taken for delivery were 8595 and 9898 MU and 9.8 and 11.3 minutes for the
      brain and chest plans, respectively. Although the dosimetric equivalence of SIB
      to a single fraction radiosurgery might still be questionable, our preliminary
      experience of WBRT with SIB to individual brain metastases using Helical
      TomoTherapy has been encouraging. In addition, it allows synchronous irradiation
      of other involved primary or metastatic sites for palliative effect.

PMID- 19166239
TI  - Multimodality image guided total marrow irradiation and verification of the dose
      delivered to the lung, PTV, and thoracic bone in a patient: a case study.
AB  - This work reports our initial experience using multimodality image guidance to
      improve total marrow irradiation (TMI) using helical tomotherapy. We also
      monitored the details of the treatment delivery to glean information necessary
      for the implementation of future adaptive processes. A patient with metastatic
      Ewing's sarcoma underwent MRI, and bone scan imaging prior to TMI. A whole body
      kilovoltage CT (kVCT) scan was obtained for intensity modulated TMI treatment
      planning, including a boost treatment to areas of bony involvement. The delivered
      dose was estimated by using MVCT images from the helical tomotherapy treatment
      unit, compared to the expected dose distributions mapped onto the kVCT images.
      Clinical concerns regarding patient treatment and dosimetric uncertainties were
      also evaluated. A small fraction of thoracic bone volume received lower radiation
      dose than the prescribed dose. Reconstructed planned treatment volume (PTV) and
      the dose delivered to the lung were identical to planned dose. Bone scan imaging
      had a higher sensitivity for detecting skeletal metastasis compared to MR
      imaging. However the bone scan lacked sufficient specificity in three dimensions
      to be useful for planning conformal radiation boost treatments. Inclusion of
      appropriate imaging modalities improves detection of metastases, which allows the
      possibility of a radiation dose boost to metastases during TMI. Conformal
      intensity modulated radiation therapy via helical tomotherapy permitted radiation
      delivery to metastases in the skull with reduced dose to brain in conjunction
      with TMI. While TMI reduces irradiation to the lungs, onboard megavoltage
      computed tomography (MVCT) to verify accurate volumetric dose coverage to marrow
      containing thoracic bones may be essential for successful conformal TMI
      treatment.

PMID- 19166240
TI  - Total marrow irradiation with helical tomotherapy for bone marrow transplantation
      of multiple myeloma: first experience in Asia.
AB  - Three Asian patients with plasma cell myeloma stage IIIa with IgG predominant
      were selected for autologous hematopoietic cell transplantation (HSCT). Total
      marrow irradiation (TMI) tomotherapy planned with melphalan 140 mg/m2 as a
      preconditioning regimen of HSCT. Two image sets of computed tomography (CT) were
      scanned with 2.5 mm and 5 mm for the upper and lower part of the plan,
      respectively. The junction was determined and marked at 15 cm above knee on both
      thighs for upper and lower part of the plan. The clinical target volume (CTV)
      included the entire skeletal system. The planning target volume (PTV) was
      generated with with 0.8 cm for CTV(extremities) and with 0.5 cm margin for all
      other bones of CTV. A total dose of 800 cGy (200 cGy/fraction) was delivered to
      the PTV. Update to presentation, all of three patients post transplant without
      evidence of active disease were noted. During TMI treatment, one with grade 1
      vomiting, two with grade 1 nausea, one with grade 1 mucositis, and three with
      grade 1 anorexia were noted. Toxicity of treatment was scored according to the
      Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). The average for
      upper part versus lower part of PTV (Bone marrow) of CI and H-index were 1.5 and
      1.4 versus 1.2 and 1.2, respectively. The dose reduction of TMI tomotherapy to
      various OARs of head, chest, and abdomen relative to TBI varied from 31% to 74%,
      21% to 51%, and 46% to 63%, respectively. The maximum average value of
      registration for upper torso versus lower extremities in different translation
      directions were 5.1 mm versus 4.1 mm for pretreatment and 1.5 mm versus 0.7 mm
      for post-treatment, respectively. The average treatment time for the upper versus
      lower part in beam-on time, setup time, and MVCT registration time took roughly
      49.9, 23.3, and 11.7 min versus 11.5, 10.0, and 7.3 min, respectively. The margin
      of PTV could be less than 1 cm under good fixation and close position
      confirmation with MVCT. Antiemetics should be prescribed in the whole course of
      TMI for emesis prevention. TMI technique replaced TBI technique with 8 Gy as
      conditioning regiment for multiple myeloma could be acceptable for the Asian and
      the outcomes were feasible for the Asian.

PMID- 19166241
TI  - Quality assurance of an image guided intracranial stereotactic positioning
      system.
AB  - This work reports on the development and testing of an intracranial stereotactic
      patient positioning system (ISPPS) for Tomotherapy. The ISPPS consists of the
      combination of a head frame, head frame couch interface (HCI), megavoltage CT
      (MVCT), and optical tracking camera system. Three quality assurance tests were
      designed to quantify the positioning system's ability to localize an intracranial
      target. The first two of these tests were designed to determine (a) the ability
      of the MVCT to detect a known shift applied to an anthropomorphic phantom and (b)
      the precision of fixing the phantom to the treatment couch via a head frame and
      specially designed head frame couch interface. A system verification test, using
      a phantom and EDR2 film, was used to determine the overall delivery precision
      through comparison of a measured dose distribution on film to calculated dose.
      The average net translational difference between a known shift applied to a
      phantom and that detected by MVCT image fusion was 0.62 mm. Setup reproducibility
      of the head frame was measured with both MVCT and optical tracking. The frame
      setup precision was found to be well within 1 mm for translations as well as
      rotations. A system delivery verification test in phantom using film showed
      spatial agreement between planned and delivered dose distributions to within 1
      mm.

PMID- 19166242
TI  - Modeling combined radiopharmaceutical therapy: a linear optimization framework.
AB  - In this paper, we investigate a previously proposed mathematical model describing
      the effects that an innovative combined radiopharmaceutical therapy might have on
      the delivery of radiation to the tumor and limiting critical organs. While
      focused on a specific dual agent therapy, this investigation will prove
      mathematically that for any two therapeutic radiopharmaceuticals with different
      limiting critical organs the model provides patient specific conditions under
      which combination therapy is superior to single agent therapy. In addition, this
      paper outlines general methods for calculating the amounts of administered
      radioactivity for each drug required to optimize tumor radiation dose. We also
      consider extensions of this model to include an arbitrary number of independent
      radiopharmaceuticals and/or other treatment factors.

PMID- 19166243
TI  - Growth inhibition against intracranial C6 glioma cells by stereotactic delivery
      of BCNU by controlled release from poly(D,L-lactic acid) nanoparticles.
AB  - Transferrin (Tf), an iron-transporting serum glycoprotein, which binds to
      receptors expressed at the surface of most proliferating cells with particularly
      high expression on erythroblasts and cancer cells, was chosen as the ligand to
      develop BCNU-loaded biodegradable poly(D,L-lactic acid) nanoparticles (NPs)
      containing a ligand, which specifically binds to glioma cells, and their anti
      tumor ability was evaluated using a C6 glioma model. In vitro drug release
      behavior demonstrated that BCNU-loaded PLA NPs show certain sustained release
      characteristics. NPs with low molecular weight PLA showed a higher burst effect
      and a significantly faster drug release from PLA samples. The biodistribution of
      Tf-coated nanoparticles investigated by 99Tc-labeled SPECT showed that the
      surface-containing transferrin PLA nanoparticles were concentrated in the brain
      and no radioactive foci could be found outside the brain. Inhibition of tumor
      growth in the C6 tumor-bearing animal model showed that BCNU-loaded PLA NPs had
      stronger cytotoxicity and prolonged the average survival time of rats. Especially
      when treated at an early stage with a higher dosage of NPs, the average survival
      time of rats was prolonged 88.37%. Furthermore, one rat maintained normal
      behavior continuously for an observation period of up to 60 days.

PMID- 19166244
TI  - Treatment of primary liver tumors with Yttrium-90 microspheres (TheraSphere) in
      high risk patients: analysis of survival and toxicities.
AB  - This retrospective study was undertaken to obtain information regarding the
      survival and toxicities after Yttrium-90 microspheres treatment in patients with
      primary liver malignancies. Baseline, treatment, and follow-up data were
      collected and analyzed for 21 patients treated with Yttrium-90 microspheres.
      Survival analysis was then performed. The results of this study showed that
      median survival for all the patients was 120 days. Twenty of 21 patients were
      categorized as high-risk with a median survival of 114 days. It was also found
      that one high-risk patient has survived 858 days with no recurrence of disease.
      Acute grade 3-5 toxicities were recorded for nine patients and consisted of
      elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites,
      nausea, fatigue, and death. This study concluded that Yttrium-90 is a low
      toxicity, outpatient alternative for individuals with liver cancer and without
      many options. The maximal value, however, may lie in the treatment of low-risk
      patients.

PMID- 19166245
TI  - Autofluorescence videobronchoscopy (AFI) for the assessment of tumor extension in
      lung cancer.
AB  - The major objective of our study was to determine the specificity and sensitivity
      of AFI videobronchoscopy vs. white light videobronchoscopy, in the assessment of
      lung cancer extent. Secondary objective was to investigate whether or not AFI can
      reveal greater extension of the tumor, and can it influence therapy making
      decision. Autofluorescence videobronchoscopy systems are new technology for
      visualization of bronchial mucosa, and the proper indications for such systems
      will be determined in the near future. In this prospective trial we have enrolled
      27 patients with suspected lung cancer in whom we performed 108 diagnostic
      biopsies and 54 control biopsies. All patients underwent WL videobronchoscopy
      followed by Auto Fluorescence Imaging (AFI) examination of tracheobronchial tree.
      We were using videobronchoscope BF-F260 and EVIS LUCERA SPECTRUM processor unit.
      Overall specificity for AFI in the diagnostics of lung cancer was found to be
      85%, sensitivity was 90%, positive predictive value (PPV) 78%, and negative
      predictive value (NPV) 94%. Specificity, sensitivity, PPV, and NPV for WL
      videobronchoscopy in lung cancer diagnostics were 54%, 64%, 51%, and 69%,
      respectively. Relative sensitivity ratio of AFI over WL videobronchoscopy, which
      is calculated to be 1.41, confirmed superiority of AFI in lung cancer
      diagnostics. We confirmed significant correlation between the greater extension
      of the tumor (assessed with AFI) and the therapeutical decision in lung cancer
      treatment (p = 0.01). Influence of AFI on therapeutical decision was significant
      (p = 0.034). AFI videobronchoscopy system yields significantly higher sensitivity
      and specificity for the assessment of lung cancer extent than WLB
      videobronchoscopy alone. It had shown to be able to influence therapeutic option
      for lung cancer treatment. Further studies are needed to evaluate and validate
      these results.

PMID- 19166246
TI  - [The first ten years of the European convention on biomedicine and human rights:
      reflections and evaluation].
AB  - April 2007 marked the tenth anniversary of the invitation to sign the European
      Convention on Human Rights and Biomedicine. The author reflects on the importance
      of this document at international level and, particularly, for Spain.

PMID- 19166247
TI  - [The hospital as an ethical organism].
AB  - In hospital medicine, medical ethics and the ethics of health care management are
      interwoven. In other words, between the hospital as an institution and as a
      collection of individual persons. Some authors maintain that the hospital cannot
      exist as an ethical organism with its own being in a pluralist society. In this
      contribution, the author defends the view that a hospital is and behaves as a
      moral agent, and that it must do so to survive. For this, a hospital must
      publicly define its mission and philosophy, its values and principles as norms
      that make up its ethical code or ideological framework, since, to great extent,
      it is a moral, juridical and social entity. This ideology is the human project
      that the hospital owes to itself and which must inspire all those who work there.
      At the same time, it must opt for the ethical education of students and resident
      doctors who train there.

PMID- 19166248
TI  - [Person versus human being: an analysis of the main argumentative scheme? Of the
      discussion].
AB  - The value of the concept of person in bioethics has been questioned in recent
      years by authors like Singer, Engelhardt, Harris and others, who water down its
      ontological consistency by reducing it to mere qualities "in acto" like
      rationality and self-conscience. Consequently, they limit enormously the subjects
      to which it can be applied. Embryos, foetuses, children, people in coma, the
      elderly in terminal phases, among others, could not be considered persons since
      they are not completely self-conscious beings. In this article, the author
      analyses the main argumentative scheme used by these authors to support their
      assertions, discuss its validity, points out the ethical problems that arise,
      reaffirms the centrality of the concept of person and suggests ways of research
      which can provide suitable answers to this kind of reasoning.

PMID- 19166249
TI  - [The limits of consequentialist bioethics. An analysis of Peter Singer's
      proposal].
AB  - This paper shows some of the contradictions and counterintuitive consequences
      that follow from the ontological and ethical commitments on which Peter Singer's
      consequentialism and his conception of person rely.

PMID- 19166250
TI  - [Ethical relativism and the modern concept of tolerance].
AB  - History presents many examples of men and women who find themselves in a position
      of having to disobey civil law. The motives for such disobedience can only be
      founded on moral conscience, as influenced by other laws - immutable and
      recognized as true. The author studies the historical context of the appearance,
      during the Age of the Enlightenment, of a new concept: tolerance. Ceasing to
      represent the expression of the classical practical virtue of prudence,
      ideological tolerance achieves the rank of theoretical virtue. Such a pretension
      has a political in essence but also innumerable ethical consequences. An
      ideologically tolerant society is created. The author develops this paradoxical
      thesis according to which an ideologically tolerant society is not prepared to
      tolerate the idea that there might exist a truth for which to search. Today, we
      see a secularization of conscientious objection concerning two particular themes:
      military service and matters connected with the protection of human life.
      Examining the paradigmatic example of abortion, the author demonstrates how
      society is no longer capable of reflecting peacefully upon the question of the
      status of the embryo, for fear of questioning the legislative choice concerning
      its legalization. Thus, society no longer has the capability of confronting
      challenges connected to practices that are detrimental to the dignity of human
      life, the essential criteria that would allow it to face these matters having
      been declared outside the confines of future reflection.

PMID- 19166251
TI  - [Religion: obstacle or impulse for science?].
AB  - Monotheism has historically encouraged science, in so far as it considers the
      world as a God's creation at the service of human beings. Nowadays, monotheism
      finds itself opposing the developments of techno-science, which all too readily
      transforms humans into mere instruments.

PMID- 19166252
TI  - [Religious beliefs and the bioethical job].
AB  - In modern-day Spain, it is often said that possessing religious beliefs must be a
      hindrance in studying, investigating and teaching bioethics. Critics point to a
      lack of impartiality, a temptation to impose one's own beliefs and the difficulty
      in reaching consensus (so necessary in this field) as consequences of such a
      state. We analyse these so-called difficulties in this article. As regards the
      first criticism, we consider it a fallacy that merely intends to disqualify
      certain persons from participating in bioethical debate, as if no-one was not
      conditioned by their beliefs, disbeliefs or agnosticism. To accept this argument
      would be to accept the imposition of one point of view to the detriment of
      bioethical pluralism. Indeed, the mere acceptance would condemn bioethical
      dialogue, which should be based on the freedom to rationally express one's point
      of view so that it may be analysed by others, not rejected a priori because of
      where or whom it comes from. As regards the second criticism, it must be said
      that as long as the beliefs of an individual, whether religious, atheistic or
      agnostic, are put forward in a way that can be easily understood by an
      interlocutor, they should not be rejected out of hand but listened to as a
      contribution to intellectual debate. Lastly, ethical reasoning elaborated and
      deduced from strictly religious sources, may point to basic, universal, moral
      intuitions that may help in the rational discussion of bioethics without
      producing confusion and discord amongst thinking persons. The study also analyses
      the relations between minimal and maximal bioethics with the religion,
      emphasising that the last, especially in its Christian form and rational efforts
      to make the human condition more intelligible, may well be an antidote against
      shallow thinking that so limits the bioethical debate.

PMID- 19166253
TI  - [Trust as a fundamental key for management in the service of people: Robert
      Spaemann's work].
AB  - In the present paper, we analyse the role of trust in the search for truthful
      health management in the service of people, bearing in mind the considerations of
      Robert Spaemann, Emeritus Professor of Ethics and Politics at the University of
      Munich. According to this author, trust is an intangible asset which helps the
      transmission of knowledge and the voluntary assumption of responsibility. In the
      first place, the transfer of knowledge, because the credibility of any
      professional involved in health management is threatened when such activity is
      carried out in a scenario in which managers may provide incentives for just the
      opposite of cooperative knowledge, so that transparency in the transmission of
      truth and "getting on" in one's career may appear in conflict. Secondly, the
      voluntary assumption of responsibilities, because the credibility of a health
      manager is lent weight when, in any contingency, he/she regularly puts the
      interests of patients before personal interests.

PMID- 19166254
TI  - [Construction vs. development: the source of our misunderstandings concerning the
      beginning of life].
AB  - This essay argues that the failure of our public debates over abortion and embryo
      destructive research is due, to a large extent, not to different valuation of
      individual human life but to different conceptions and intuitions concerning the
      process of gestation, one group treating the process as construction and another
      treating it as development. These two incompatible models of reproduction are
      shown to explain the various positions commonly encountered in these life-related
      debates. Finally, the historical, theoretical, and intuitive strengths of each
      model are examined.

PMID- 19166255
TI  - [The woman-mother, a recovered value].
AB  - In a society based on efficiency and productivity, rediscovering the role of the
      woman-mother as a human being with special traits that allow her to understand
      people as they really are, and what needs and aspirations they have is essential.
      Women manifest an affective, cultural and spiritual kind of maternity of
      incalculable value due to its influence on the development of each individual. At
      the same time, women must be allowed to play a full part in political and social
      ambits, working as equals along side men.

PMID- 19166256
TI  - [Experimentation with women: science fiction or reality?].
AB  - Many people will not have heard about the experimentation that has been, and
      continues to be, carried out on women, because much of the media makes no mention
      of the matter. Just a few examples that could be mentioned are experimentation
      with the contraceptive pill, forced sterilization, egg donation, surrogate
      motherhood, kidney and other organ donation, and unnecessary therapy and surgery.
      In a few cases such experimentation could well be termed exploitation of women,
      with all kinds of excuses or humanitarian reasons, and sometimes communitarian
      purposes and even reasons concerning possible benefits for the whole of society,
      being mentioned. The present work aims to stimulate reflection about some types
      of research which can only be regarded as exploitation of women.

PMID- 19166257
TI  - [Equitable AIDS prevention].
AB  - According to the December 2006 UNAIDS report, by the end of 2006 approximately
      39.5 million people in the world were living with HIV/AIDS. In 2006, about 4.3
      million people worldwide became infected and 8,000 people a day died of HIV/AIDS.
      About half of the new infections occurred in young people aged between 15 and 24.
      In December 2004, The Lancet published an international consensus on the "ABC
      strategy" for AIDS prevention, which can be considered a turning point in
      HIV/AIDS prevention. The Lancet Consensus recommends segmenting information,
      depending on the audience to be targeted. The Consensus insisted that the first
      priority for young people should be to encourage "abstinence" or postponing the
      start of sexual relations. Once sexual relations are initiated, a return to
      "abstinence" or maintaining mutually monogamous sexual relations with an
      uninfected person should be encouraged. If the campaigns targets people at high
      risk of exposure to HIV exposure the first priority should be to encourage the
      correct and consistent use of condoms, but warning them that condom use can
      reduce, but not eliminate, the risk of infection. Little attention and almost no
      resources have been devoted to "risk avoidance " interventions, such as delaying
      the start of sexual relations or maintaining mutually monogamous sexual relations
      (components A and B). Nevertheless, scientific evidence indicates that risk
      avoidance; which has been largely neglected in the international response to the
      disease, is probably what is desperately needed to stop the HIV/AIDS epidemic and
      alleviate its consequences at all levels.

PMID- 19166258
TI  - [AIDS: a cause and consequence of poverty].
AB  - The widespread consequences of the HIV/AIDS pandemic are well known; besides the
      obvious reduction in life expectancy, the epidemic has caused a decrease in
      economic productivity that has in turn affected entire sectors of society,
      including agricultural and educational fields. There is a tendency to associate
      HIV/AIDS with poverty. In other words, an increase in the poverty rate correlates
      with an increase in the probability of HIV/AIDS. This would seem to suggest that
      if the conditions of society could be improved, the spread of new infections
      could be checked. Although this may sound attractive, and may even be thought
      necessary and just, it would be a mistake to consider that a reduction in poverty
      is sufficient to prevent HIV/AIDS. HIV/AIDS is not necessarily, nor exclusively,
      " an infection and a disease of the poor. " Indeed, people with high economic and
      educational status have also been linked with a higher risk of developing
      HIV/AIDS. Prevention should be emphasized, taking into consideration that if this
      approach is to work there should be a change in current sexual behaviour. In
      order of priority, teenagers should be recommended to delay having sex. Partners
      should form a relationship based on trust and faithfulness. Lastly, those who do
      not accept these preventive measures should be advised that the use of condoms
      may "reduce risks" but not eliminate completely the spread of the disease. All of
      these preventive measures have been demonstrated as key aspects in the fight
      against HIV/AIDS in several countries. No country has been able to reduce the
      prevalence of HIV/AIDS relying solely on the promotion of condoms.

PMID- 19166259
TI  - [AIDS and social justice: pharmaceutical industry and economics].
AB  - This article takes a broad look at the complicated framework of relationships
      between the third world and pharmaceutical companies. In the first part of the
      work reference is made to the poverty of these countries, their lack of education
      in terms of health, the scarcity of basic hygiene, and their greatly limited
      access to medicines, especially those for treating AIDS. The article then
      proceeds to the issue of the pharmaceutical companies' degree of responsibility
      for the reduced availability of medicines in certain areas of the world. One of
      the factors that most limits access to medicines is their price, and many sectors
      of society propose taking action on the patents of drugs (rescinding or limiting
      them) in order to lower their price. However, the problem of patent exemption is
      more complicated than it seems at first glance, and comes with its own risks. If,
      for lack of funds or the uncertainty concerning a return on the capital invested,
      pharmaceutical companies discontinue research and development of new drugs, AIDS
      therapy would worsen. It is imperative and urgent to develop new drugs against
      the AIDS because of its resistance to the drugs currently available. The article
      concludes with the pharmaceutical industry's effort to look for possible forms of
      collaboration with developing countries.

PMID- 19166260
TI  - Embryotoxicity of retene in cotreatment with 2-aminoanthracene, a cytochrome
      P4501A inhibitor, in rainbow trout (Oncorhynchus mykiss).
AB  - Environmentally relevant mixtures of polycyclic aromatic hydrocarbons (PAHs;
      e.g., crude oils) are often rich in alkyl-PAHs, such as retene (7-isopropyl-1
      methylphenanthrene), which produce dioxin-like toxicity in fish embryos. The
      mechanism of alkyl-PAH toxicity is not well understood but was previously thought
      to be mediated by cytochrome P4501A (CYPIA) enzymes. To understand the role of
      CYP1A in retene toxicity, we coexposed free-swimming rainbow trout (Oncorhynchus
      mykiss) embryos to 100 microg/L of retene and to a range of concentrations of 2
      aminoanthracene (2AA; a known CYP1A inhibitor). Ethoxyresorufin-O-deethylase
      (EROD) assays of juvenile trout coexposed to 2AA and retene confirmed that 2AA
      inhibited CYP1A (median inhibitory concentration [IC50] for 2AA, 62 microg/L). In
      two independent trials, 2AA, both alone and in cotreatment with retene, produced
      a concentration-dependent increase in toxicity to embryonic trout. The toxicity
      resulting from 2AA alone is, to our knowledge, the first reported for embryonic
      stages of fish, with median lethal concentrations (LC50s) of 19 and 125 microg/L
      and overall sublethal median effective concentrations (EC50s) of 17 and 38
      microg/L. Toxicity increased in embryos coexposed to retene and 2AA, resulting in
      LC50s of 14 and 17 microg/L of 2AA and overall EC50s of 7 and 3 microg/L of 2AA.
      The exposure-response curves for 2AA alone and for 2AA with retene were parallel,
      suggesting a common mode of action between the two treatment regimes and between
      retene and 2AA. Taken together with the juvenile EROD data, the toxicity of 2AA
      alone and in cotreatment with retene may be EROD (CYP1A) independent. The mixture
      toxicity was not consistent with previous coexposures to CYP1A inducers and
      inhibitors, suggesting that the current risk assessment model may not be a good
      predictor of PAH mixture toxicity.

PMID- 19166262
TI  - Development and application of a rapid amphipod reproduction test for sediment
      quality assessment.
AB  - Melita plumulosa is an epibenthic, detritivorous amphipod native to eastern
      Australia that has been adopted as a test organism for toxicity evaluations of
      contaminated estuarine sediments. In the present study, a 13-d amphipod
      reproduction test was developed that encompasses gametogenesis, fertilization,
      and embryo development before hatching. The primary endpoints for the test are
      fecundity (measured as the number of embryos per individual surviving female) and
      a fecundity index (fecundity multiplied by the stage of embryo development). This
      new test has been employed to scrutinize the sediments from a metal-contaminated
      coastal lagoon. Lake Macquarie (NSW, Australia) is a large, saltwater lagoon that
      has received metal pollution over many decades, leading to a concentration
      gradient of trace metals, including Pb, Zn, Cd, and Cu, in the sediments. Within
      one of the northern bays (Warners Bay), the concentrations of these metals either
      border on or exceed sediment quality guideline values prescribed by Australian
      and New Zealand Guidelines for Fresh and Marine Water Quality. In trials with the
      13-d amphipod reproduction test, Warners Bay sediments significantly reduced
      fecundity in the test species. Subsequent tests with clean sediments spiked
      singly with Pb, Zn, or Cu indicated that no single metal was responsible for the
      observed toxicity in the field sediments. However, sediments spiked with various
      combinations of Pb, Zn, Cd, and Cu indicated that Zn in combination with one or
      more of the other metals was responsible for the reproductive toxicity observed
      in Warners Bay sediments. In all these tests, measured metal concentrations in
      overlying water and pore water were low, thus confirming that the observed
      effects on reproduction could be attributed to dietary exposure to metals.

PMID- 19166263
TI  - Data sources for improving estimates of the global burden of injuries: call for
      contributors.

PMID- 19166264
TI  - Conducting unlinked anonymous HIV surveillance in developing countries: ethical,
      epidemiological, and public health concerns.

PMID- 19166265
TI  - Condom access in South African schools: law, policy, and practice.

PMID- 19166266
TI  - Reduced glomerular filtration rate and its association with clinical outcome in
      older patients at risk of vascular events: secondary analysis.
AB  - BACKGROUND: Reduced glomerular filtration rate (GFR) is associated with increased
      cardiovascular risk in young and middle aged individuals. Associations with
      cardiovascular disease and mortality in older people are less clearly
      established. We aimed to determine the predictive value of the GFR for mortality
      and morbidity using data from the 5,804 participants randomized in the
      Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). METHODS AND
      FINDINGS: Glomerular filtration rate was estimated (eGFR) using the Modification
      of Diet in Renal Disease equation and was categorized in the ranges ([20-40], [40
      50], [50-60]) >or= 60 ml/min/1.73 m(2). Baseline risk factors were analysed by
      category of eGFR, with and without adjustment for other risk factors. The
      associations between baseline eGFR and morbidity and mortality outcomes, accrued
      after an average of 3.2 y, were investigated using Cox proportional hazard models
      adjusting for traditional risk factors. We tested for evidence of an interaction
      between the benefit of statin treatment and baseline eGFR status. Age, low
      density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, C
      reactive protein (CRP), body mass index, fasting glucose, female sex, histories
      of hypertension and vascular disease were associated with eGFR (p = 0.001 or
      less) after adjustment for other risk factors. Low eGFR was independently
      associated with risk of all cause mortality, vascular mortality, and other
      noncancer mortality and with fatal and nonfatal coronary and heart failure events
      (hazard ratios adjusted for CRP and other risk factors (95% confidence intervals
      [CIs]) for eGFR < 40 ml/min/1.73m(2) relative to eGFR >or= 60 ml/min/1.73m(2)
      respectively 2.04 (1.48-2.80), 2.37 (1.53-3.67), 3.52 (1.78-6.96), 1.64 (1.18
      2.27), 3.31 (2.03-5.41). There were no nominally statistically significant
      interactions (p < 0.05) between randomized treatment allocation and eGFR for
      clinical outcomes, with the exception of the outcome of coronary heart disease
      death or nonfatal myocardial infarction (p = 0.021), with the interaction
      suggesting increased benefit of statin treatment in subjects with impaired GFRs.
      CONCLUSIONS: We have established that, in an elderly population over the age of
      70 y, impaired GFR is associated with female sex, with presence of vascular
      disease, and with levels of other risk factors that would be associated with
      increased risk of vascular disease. Further, impaired GFR is independently
      associated with significant levels of increased risk of all cause mortality and
      fatal vascular events and with composite fatal and nonfatal coronary and heart
      failure outcomes. Our analyses of the benefits of statin treatment in relation to
      baseline GFR suggest that there is no reason to exclude elderly patients with
      impaired renal function from treatment with a statin.

PMID- 19166267
TI  - Integrated ecosystem assessments: developing the scientific basis for ecosystem
      based management of the ocean.

PMID- 19166268
TI  - Cell lineages and the logic of proliferative control.
AB  - It is widely accepted that the growth and regeneration of tissues and organs is
      tightly controlled. Although experimental studies are beginning to reveal
      molecular mechanisms underlying such control, there is still very little known
      about the control strategies themselves. Here, we consider how secreted negative
      feedback factors ("chalones") may be used to control the output of multistage
      cell lineages, as exemplified by the actions of GDF11 and activin in a self
      renewing neural tissue, the mammalian olfactory epithelium (OE). We begin by
      specifying performance objectives-what, precisely, is being controlled, and to
      what degree-and go on to calculate how well different types of feedback
      configurations, feedback sensitivities, and tissue architectures achieve control.
      Ultimately, we show that many features of the OE-the number of feedback loops,
      the cellular processes targeted by feedback, even the location of progenitor
      cells within the tissue-fit with expectations for the best possible control. In
      so doing, we also show that certain distinctions that are commonly drawn among
      cells and molecules-such as whether a cell is a stem cell or transit-amplifying
      cell, or whether a molecule is a growth inhibitor or stimulator-may be the
      consequences of control, and not a reflection of intrinsic differences in
      cellular or molecular character.

PMID- 19166269
TI  - A novel function for fragile X mental retardation protein in translational
      activation.
AB  - Fragile X syndrome, the most frequent form of inherited mental retardation, is
      due to the absence of Fragile X Mental Retardation Protein (FMRP), an RNA-binding
      protein involved in several steps of RNA metabolism. To date, two RNA motifs have
      been found to mediate FMRP/RNA interaction, the G-quartet and the "kissing
      complex," which both induce translational repression in the presence of FMRP. We
      show here a new role for FMRP as a positive modulator of translation. FMRP
      specifically binds Superoxide Dismutase 1 (Sod1) mRNA with high affinity through
      a novel RNA motif, SoSLIP (Sod1 mRNA Stem Loops Interacting with FMRP), which is
      folded as three independent stem-loop structures. FMRP induces a structural
      modification of the SoSLIP motif upon its interaction with it. SoSLIP also
      behaves as a translational activator whose action is potentiated by the
      interaction with FMRP. The absence of FMRP results in decreased expression of
      Sod1. Because it has been observed that brain metabolism of FMR1 null mice is
      more sensitive to oxidative stress, we propose that the deregulation of Sod1
      expression may be at the basis of several traits of the physiopathology of the
      Fragile X syndrome, such as anxiety, sleep troubles, and autism.

PMID- 19166270
TI  - Role of a novel PH-kinase domain interface in PKB/Akt regulation: structural
      mechanism for allosteric inhibition.
AB  - Protein kinase B (PKB/Akt) belongs to the AGC superfamily of related
      serine/threonine protein kinases. It is a key regulator downstream of various
      growth factors and hormones and is involved in malignant transformation and chemo
      resistance. Full-length PKB protein has not been crystallised, thus studying the
      molecular mechanisms that are involved in its regulation in relation to its
      structure have not been simple. Recently, the dynamics between the inactive and
      active conformer at the molecular level have been described. The maintenance of
      PKB's inactive state via the interaction of the PH and kinase domains prevents
      its activation loop to be phosphorylated by its upstream activator,
      phosphoinositide-dependent protein kinase-1 (PDK1). By using a multidisciplinary
      approach including molecular modelling, classical biochemical assays, and Forster
      resonance energy transfer (FRET)/two-photon fluorescence lifetime imaging
      microscopy (FLIM), a detailed model depicting the interaction between the
      different domains of PKB in its inactive conformation was demonstrated. These
      findings in turn clarified the molecular mechanism of PKB inhibition by AKT
      inhibitor VIII (a specific allosteric inhibitor) and illustrated at the molecular
      level its selectivity towards different PKB isoforms. Furthermore, these findings
      allude to the possible function of the C-terminus in sustaining the inactive
      conformer of PKB. This study presents essential insights into the quaternary
      structure of PKB in its inactive conformation. An understanding of PKB structure
      in relation to its function is critical for elucidating its mode of activation
      and discovering how to modulate its activity. The molecular mechanism of
      inhibition of PKB activation by the specific drug AKT inhibitor VIII has critical
      implications for determining the mechanism of inhibition of other allosteric
      inhibitors and for opening up opportunities for the design of new generations of
      modulator drugs.

PMID- 19166272
TI  - Biological systems from an engineer's point of view.

PMID- 19166271
TI  - A point mutation in the hair cell nicotinic cholinergic receptor prolongs
      cochlear inhibition and enhances noise protection.
AB  - The transduction of sound in the auditory periphery, the cochlea, is inhibited by
      efferent cholinergic neurons projecting from the brainstem and synapsing directly
      on mechanosensory hair cells. One fundamental question in auditory neuroscience
      is what role(s) this feedback plays in our ability to hear. In the present study,
      we have engineered a genetically modified mouse model in which the magnitude and
      duration of efferent cholinergic effects are increased, and we assess the
      consequences of this manipulation on cochlear function. We generated the
      Chrna9L9'T line of knockin mice with a threonine for leucine change (L9'T) at
      position 9' of the second transmembrane domain of the alpha9 nicotinic
      cholinergic subunit, rendering alpha9-containing receptors that were
      hypersensitive to acetylcholine and had slower desensitization kinetics. The
      Chrna9L9'T allele produced a 3-fold prolongation of efferent synaptic currents in
      vitro. In vivo, Chrna9L9'T mice had baseline elevation of cochlear thresholds and
      efferent-mediated inhibition of cochlear responses was dramatically enhanced and
      lengthened: both effects were reversed by strychnine blockade of the
      alpha9alpha10 hair cell nicotinic receptor. Importantly, relative to their wild
      type littermates, Chrna9(L9'T/L9'T) mice showed less permanent hearing loss
      following exposure to intense noise. Thus, a point mutation designed to alter
      alpha9alpha10 receptor gating has provided an animal model in which not only is
      efferent inhibition more powerful, but also one in which sound-induced hearing
      loss can be restrained, indicating the ability of efferent feedback to ameliorate
      sound trauma.

PMID- 19166273
TI  - Managed care interventions for improving outcomes in acute heart failure
      syndromes.
AB  - Acute heart failure syndromes (AHFS) are characterized by a gradual or rapid
      progression of the signs and symptoms of heart failure (HF), resulting in a need
      for urgent therapy. Patients with AHFS comprise approximately 20% of all HF
      patients and represent the most severely ill and undermanaged subpopulation of
      patients with HF. Despite the rising prevalence and costs associated with AHFS,
      the disease remains largely undermanaged, partially as a result of a failure to
      initiate treatment with proven therapies, such as beta-blockers, angiotensin
      converting enzyme inhibitors, and angiotensin receptor blockers, during
      hospitalization or soon after discharge. Although professional organizations have
      been striving to improve the state of care for AHFS by providing at least some
      level of consensus and evidence-based treatment recommendations, the gap between
      the clinical evidence and actual practice is growing. Appropriate disease
      assessment, followed by the implementation of life-saving therapies, is the key
      to improving outcomes. Managed care initiatives, such as improved quality
      measures, disease management programs, patient education efforts, hospital
      discharge checklists, and pharmacy-led interventions to enhance medication
      compliance, provide potential solutions for combating the alarming rise of
      morbidity, mortality, and costs associated with this disease.

PMID- 19166274
TI  - Coalescence of silver nanoparticles at room temperature: unusual crystal
      structure transformation and dendrite formation induced by self-assembly.
AB  - It was found that during the evaporation of water from a droplet of a silver
      nanoparticles dispersion a self-assembly process leads to the coalescence of the
      nanoparticles at room temperature and eventually results in a 3D, micrometer
      sized dendrite. Direct in situ HR-TEM observation of coalescence events of
      individual nanoparticles revealed that during this process a transformation of
      the nanoparticles' crystal structure takes place, from the common fcc silver
      structure to the unusual hcp structure. It was found that even-though a majority
      of the nanoparticles in the dispersion have the fcc structure the obtained
      dendrites are characterized by the hcp structure, reflecting the crystal
      structure transformation due to the coalescence process.

PMID- 19166275
TI  - Formation of a three-dimensional multicellular assembly using magnetic
      patterning.
AB  - We demonstrate a facile approach to design three-dimensional cellular assembly of
      tunable size and controlled geometry with applications for tissue engineering.
      Three-dimensional cell patterning was performed using external magnetic forces,
      without the need for substrate chemical or physical modifications. Human
      endothelial progenitor cells and mouse macrophages were magnetically labeled
      using anionic citrate-coated iron oxide nanoparticles. Two magnetic tips were
      designed, and their magnetic field cartographies were calibrated. The focalized
      magnetic force generated ensured an efficient entrapment of the cells at the tips
      vicinity. By tuning the magnetic field gradient geometry and intensity, the
      magnetic cellular load, and the number of cells, we fully described the formation
      of the three-dimensional multicellular assemblies, and estimated the
      corresponding packing factor for a large range of experimental conditions.

PMID- 19166276
TI  - Superparamagnetic iron oxide nanoparticles encapsulated in biodegradable
      thermosensitive polymeric micelles: toward a targeted nanomedicine suitable for
      image-guided drug delivery.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) have been receiving great
      attention lately due to their various biomedical applications, such as in MR
      imaging and image guided drug delivery. However, their systemic administration
      still remains a challenge. In this study, the ability of biodegradable
      thermosensitive polymeric micelles to stably encapsulate hydrophobic oleic-acid
      coated SPIONs (diameter 5-10 nm) was investigated, to result in a system
      fulfilling the requirements for systemic administration. The micelles were
      composed of amphiphilic, thermosensitive, and biodegradable block copolymers of
      poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide dilactate] (mPEG
      b-p(HPMAm-Lac2)). The encapsulation was performed by addition of one volume of
      SPIONs in THF to nine volumes of a cold aqueous mPEG-b-p(HPMAm-Lac2) solution (0
      degrees C; below the cloud point of the polymer), followed by rapid heating of
      the resulting mixture to 50 degrees C, to induce micelle formation ("rapid
      heating" procedure). Dynamic light scattering (DLS) measurements revealed that
      approximately 200 nm particles (PDI=0.2) were formed, while transmission electron
      microscopy (TEM) analysis demonstrated that clusters of SPIONs were present in
      the core of the micelles. A maximum loading of 40% was obtained, while magnetic
      resonance imaging (MRI) scanning of the samples demonstrated that the SPION
      loaded micelles had high r2 and r2* relaxivities. Furthermore, the r2* values
      were found to be at least 2-fold higher than the r2 values, confirming the
      clustering of the SPIONs in the micellar core. The particles showed excellent
      stability under physiological conditions for 7 days, even in the presence of
      fetal bovine serum. This, together with their ease of preparation and their size
      of approximately 200 nm, makes these systems highly suitable for image-guided
      drug delivery.

PMID- 19166277
TI  - Reversible gelation of rod-like viruses grafted with thermoresponsive polymers.
AB  - The synthesis and selected macroscopic properties of a new model system
      consisting of poly(N-isopropylacrylamide) (PNIPAM)-coated rod-like fd virus
      particles are presented. The sticky rod-like colloids can be used to study effect
      of particle shape on gelation transition, the structure and viscoelasticity of
      isotropic and nematic gels, and to make both open isotropic as well as ordered
      nematic particle networks. This model system of rod-like colloids, for which the
      strength of attraction between the particles is tunable, is obtained by
      chemically grafting highly monodisperse rod-like fd virus particles with
      thermoresponsive polymers, e.g. PNIPAM. At room temperature, suspensions of the
      resulting hybrid PNIPAM-fd are fluid sols which are in isotropic or liquid
      crystalline phases, depending on the particle concentration and ionic strength.
      During heating/cooling, the suspensions change reversibly between sol and gel
      state near a critical temperature of approximately 32 degrees C, close to the
      lower critical solution temperature of free PNIPAM. The so-called nematic gel,
      which exhibits a cholesteric feature, can therefore be easily obtained. The
      gelation behavior of PNIPAM-fd system and the structure of the nematic gel have
      been characterized by rheology, optical microscopy and small-angle X-ray
      scattering.

PMID- 19166278
TI  - Structural evolution of the dihydrate to anhydrate crystalline transition of
      trehalose as measured by wide-angle X-ray scattering.
AB  - Wide-angle X-ray scattering measurements were performed to record structural
      changes during the transition from trehalose dihydrate to crystalline anhydrous
      alpha-trehalose. The results show that large dihydrate crystals rearrange into
      smaller sized alpha crystals; from the peak widths we calculate a crystallite
      size of typically approximately 40 trehalose molecules. We find that the
      dehydration probably takes place in a two-step process with different time scales
      for both the water removal step and the molecule rearrangement step. This
      suggests that there is crystal rearrangement in the dry state some 60 degrees C
      below the dry glass transition temperature of trehalose, which is unusual for a
      relatively large and strongly interacting molecule.

PMID- 19166279
TI  - Properties of the thiobase pairs hydrogen bridges: a theoretical study.
AB  - The characteristics of the hydrogen bridges in the base pairs with S --> O
      substitution have been studied and the comparisons with the unmodified systems
      considered. The modifications induced by the sulfur atom in the structures,
      energies, and atomic charges have been evidenced and the energetic effects
      revaluated for the first time. Their effects on the hydrogen transfer from a base
      to the other and the relevance of these static and dynamical features for
      biological properties have been suggested.

PMID- 19166280
TI  - The role of GLUT1 in the sugar-induced dielectric response of human erythrocytes.
AB  - We propose a key role for the glucose transporter 1 (GLUT1) in mediating the
      observed changes in the dielectric properties of human erythrocyte membranes as
      determined by dielectric spectroscopy. Cytochalasin B, a GLUT1 transport
      inhibitor, abolished the membrane capacitance changes in glucose-exposed red
      cells. Surprisingly, D-fructose, known to be transported primarily by GLUT5,
      exerted similar membrane capacitance changes at increasing D-fructose
      concentrations. In order to evaluate whether the glucose-mediated membrane
      capacitance changes originated directly from intracellularly bound adenosine
      triphosphate (ATP) or other components of the glycolysis process, we studied the
      dielectric responses of swollen erythrocytes with a decreased ATP content and of
      nucleotide-filled ghosts. Resealed ghosts containing physiological concentrations
      of ATP yielded the same glucose-dependent capacitance changes as biconcave intact
      red blood cells, further supporting the finding that ATP is the effector of the
      glucose-mediated dielectric response where the ATP concentration is also the
      mediating factor in swollen red blood cells. The results suggest that ATP binding
      to GLUT1 elicits a membrane capacitance change that increases with the applied
      concentration gradient of D-glucose. A simplified model of the membrane
      capacitance alteration with glucose uptake is proposed.

PMID- 19166281
TI  - Density functional theory study of the reaction mechanism for competitive carbon
      hydrogen and carbon-halogen bond activations catalyzed by transition metal
      complexes.
AB  - Carbon-hydrogen and carbon-halogen bond activations between halobenzenes and
      metal centers were studied by density functional theory with the nonempirical
      meta-GGA Tao-Perdew-Staroverov-Scuseria functional and an all-electron
      correlation-consistent polarized valence double-zeta basis set. Our calculations
      demonstrate that the hydrogen on the metal center and halogen in halobenzene
      could exchange directly through a kite-shaped transition state. Transition states
      with this structure were previously predicted to have high energy barriers (J.
      Am. Chem. Soc. 2005, 127, 279), and this prediction misled others in proposing a
      mechanism for their recent experimental study (J. Am. Chem. Soc. 2006, 128,
      3303). Furthermore, other halo-carbon activation pathways were found in the
      detailed mechanism for the competitive reactions between cationic titanium
      hydride complex [Cp*((t)Bu(3)P=N)TiH](+) and chlorobenzene under different
      pressure of H(2). These pathways include the ortho-C-H and Ti-H bond activations
      for the formation and release of H(2) and the indirect C-Cl bond activation via
      beta-halogen elimination for the movement of the C(6)H(4) ring and the formation
      of a C-N bond in the observed final product. A new stable isomer of the observed
      product with a similar total energy and an unexpected bridging between the Cp*
      ring and the metal center by a phenyl ring is also predicted.

PMID- 19166282
TI  - Liquid crystalline phases self-organized from a surfactant-like ionic liquid
      C(16)mimCl in Ethylammonium nitrate.
AB  - The aggregation behavior of a surfactant-like ionic liquid, 1-hexadecyl-3
      methylimidazolium chloride (C(16)mimCl), in a room temperature ionic liquid
      ethylammonium nitrate (EAN) has been investigated. With increasing C(16)mimCl
      concentration, a series of ordered aggregates including micelles, normal
      hexagonal (H(1)), lamellar (L(alpha)), and reverse bicontinuous cubic (V(2))
      liquid crystalline (LC) phases can be detected over a large temperature range by
      using polarized optical microscopy (POM) and small-angle X-ray scattering (SAXS)
      techniques. When comparing such a phase behavior with that of the
      C(16)mimCl/H(2)O binary system, an additional V(2) phase is identified and could
      be attributed to the different affinities of C(16)mimCl to EAN and water. Higher
      temperatures induce smaller lattice spacing for the LC phases, which may be due
      to the softening of the solvophobic chains of C(16)mimCl molecules. Both the
      imidazolium ring structure and alkyl chain of C(16)mimCl molecule are proved to
      play important roles for the LC phase formation. Dissipative particle dynamic
      simulations are also carried out at room temperature, and the obtained intuitive
      three-dimensional (3D) models can help us better understand the self-assembled
      structures, which are considered to be supplements for the experimental results.

PMID- 19166283
TI  - Molecular dynamics simulation of the low-temperature partial oxidation of CH4.
AB  - Low-temperature partial oxidation of methane was investigated using reactive
      molecular dynamics (MD) and quantum mechanical (QM) methods. In particular, the
      ReaxFF hydrocarbon force field [Chenoweth, K.; et al. J. Phys. Chem. A 2008, 112,
      1040] was employed to simulate a [20 CH(4) + 10 O(2)] model system at 500 degrees
      C. The chemical mechanism of the partial oxidation of methane was proposed on the
      basis of analysis of the computed trajectory of this model system. The partial
      oxidation of methane was observed to be initiated by the abstraction of hydrogen
      from CH(4) by O(2) and the atomization of CH(4) itself. Subsequent radical
      recombination between hydrogen atoms and the dehydrogenation of CH(4) were the
      primary pathways by which H(2) was formed. In agreement with current models of
      low-temperature combustion, radicals including H(3)C-OO and H(2)C-OO were also
      observed during the MD simulation. The observed reaction mechanism was
      subsequently analyzed using QM methods. For instance, structural features of
      prominent radical species observed during the MD simulation were analyzed using
      density functional theory (DFT) and coupled-cluster (CCSD(T)) methods. Enthalpies
      of reaction of all observed chemical processes were calculated using DFT and the
      W1 composite method. Where possible, comparisons with experimental data were
      made.

PMID- 19166284
TI  - Technique for microfabrication of polymeric-based microchips from an SU-8 master
      with temperature-assisted vaporized organic solvent bonding.
AB  - Novel means of fabricating polymeric microfluidic devices are presented. An SU-8
      master is applied in two-stage embossing, followed by vaporized organic solvent
      bonding. The primary master is created by standard photolithography; the
      inexpensive SU-8 primary master is used in a two-stage process to generate
      microfeatures in hard polymers. A vaporized solvent bonding technique that
      readily produces complete microfluidic chips, without the need of a sacrificial
      layer to prevent channel deformation, was used to form complete multilayer
      microfluidic devices. This technique provides a more direct method to generate
      hard polymer microfluidic chips than classical techniques and therefore is highly
      amenable to rapid prototyping. The technique lends itself readily to many
      polymers, facilitating device production for a variety of applications, even
      permitting hybrid polymer chips, and provides a rapid, cost-effective, simple,
      and versatile approach to the production of polymer-based microdevices. The
      fabrication technique was tested to build microchips to perform several analyses,
      including chromatographic separations and a quantitative indicator assay. High
      separation efficiencies of 10,000-45,000 plates/m were obtained using the
      fabricated liquid chromatography (LC) microchip. The fabrication method was also
      tested in building a passive micromixer that contained high-density microfeatures
      and required three polymer layers. A glycine assay using o-phthaldialdehyde (OPA)
      was performed in the micromixer. With glycine concentrations ranging from 0.0 to
      2.6 microM, a linear calibration plot was obtained with a detection limit of
      0.032 microM.

PMID- 19166285
TI  - Novel polythreaded coordination polymer: from an armed-polyrotaxane sheet to a 3D
      polypseudorotaxane array, photo- and thermochromic behaviors.
AB  - A novel coordination compound, {[Cd(BDC)(Bpybc)(1.5)].10H(2)O}(n), obtained by
      the reaction of CdCl(2) with 1,1'-bis(4-carboxybenzyl)-4,4'-bipyridinium
      dichloride (H(2)BpybcCl(2)) and 1,4-benzenedicarboxylic acid (H(2)BDC), contains
      1D polymeric chains that are comprised of alternating rings and rods and dangling
      lateral arms. These 1D polymeric motifs are interlaced via rotaxane-like
      mechanical linkages to give 2D armed-polyrotaxane sheets, which are further
      mutually polythreaded via pseudorotaxane-like mechanical linkages to form a 3D
      polypseudorotaxane array. Notably, a sandwich-type donor-acceptor-donor stacking
      is formed within each ring as a consequence of both types of polythreading in
      this species, and photoinduced and thermal-induced reduction of bipyridinium
      occurs with a color change from light yellow to blue.

PMID- 19166286
TI  - Magnetic bistability and thermochromism in a molecular Cu(II) chain.
AB  - An original magnetic bistability and a thermochromic transition are observed in a
      new Cu(II) molecular chain. Thermal structural studies reveal changes in the
      Cu(II) coordination sphere, driven by a more pronounced Jahn-Teller effect at low
      temperature. These distortions provoke a gradual color change. The structural
      study at 10 K shows a dimerization of the molecular chain, in agreement with the
      abrupt magnetic transition observed at 30 K.

PMID- 19166287
TI  - Thermopower enhancement in nanowires via junction effects.
AB  - We present thermopower measurements on free-standing, straight and "junctioned"
      gold nanowires using a micromachined thermoelectric workbench. Measurements on
      straight 70 nm diameter gold nanowires show a thermopower similar to that of bulk
      gold; however for "junctioned" gold nanowires we observed a hitherto unreported
      peak in the thermopower near room temperature. The observed enhancement can be
      explained by approximating the "junctioned" nanowires as tunnel junctions in
      combination with Coulombic effect of the electrons crossing the junction. The
      electron transfer across the barrier can be expected to be stochastic in nature.
      Under thermal equilibrium conditions and in the absence of temperature gradient
      across the tunnel junction, the time averaged random fluctuation of the electrons
      across the tunnel junction results in a net zero voltage. However, in the
      presence of a temperature gradient across the junction, the time averaged
      fluctuation of the electrons across the junction is now offset by the tunnel
      junction thermoelectric effect and is measured by the lock-in amplifier. A
      hundredfold enhancement in the ZT of "junctioned" nanowires has been observed for
      the gold nanowires measured over several samples.

PMID- 19166288
TI  - A rhodamine-hydroxamic acid-based fluorescent probe for hypochlorous acid and its
      applications to biological imagings.
AB  - A new rhodamine-hydroxamic acid-based fluorescent chemosensor for the rapid
      detection of HOCl in aqueous media was developed. The system, which utilizes an
      irreversible HOCl-promoted oxidation reaction, responds instantaneously at room
      temperature with linear proportionality to the amount of HOCl. This system is
      highly selective for HOCl over other reactive oxygen species (ROS) and highly
      sensitive in aqueous solutions. Biological imaging studies using living cells and
      organisms (A549 cells and zebrafish) to detect HOCl are successfully
      demonstrated.

PMID- 19166289
TI  - Fabrication of highly-ordered TiO(2) nanotube arrays and their use in dye
      sensitized solar cells.
AB  - Highly ordered TiO(2) nanotubes were successfully fabricated using a nanoporous
      alumina templating method. A modified sol-gel route was used to infiltrate the
      alumina pores with Ti(OC(3)H(7))(4) which was subsequently converted into TiO(2)
      nanotubes. The average external diameter, tube lengths, and wall thickness
      achieved were 295 nm, 6-15 microm, and 21-42 nm, respectively. Diffraction data
      reveals that the nanotubes consist solely of the anatase phase. Dye-sensitized
      solar cells using TiO(2) nanotube arrays as the working electrode yielded power
      conversion efficiencies as high as 3.5% with a maximum incident photon-to-current
      conversion efficiency of 20% at 520 nm.

PMID- 19166290
TI  - Multiple multicomponent macrocyclizations (MiBs): a strategic development toward
      macrocycle diversity.

PMID- 19166291
TI  - Adsorption-driven surface segregation of the less reactive alloy component.
AB  - Counterintuitive to expectations and all prior observations of adsorbate-induced
      surface segregation of the more reactive alloy component (the one forming the
      stronger bond with the adsorbate), we show that CO adsorption at elevated
      pressures and temperatures pulls the less reactive Cu to the surface of a CuPt
      near-surface alloy. The Cu surface segregation is driven by the formation of a
      stable self-organized CO/CuPt surface alloy structure and is rationalized in
      terms of the radically stronger Pt-CO bond when Cu is present in the first
      surface layer of Pt. The results, which are expected to apply to a range of
      coinage (Cu, Ag)/Pt-group bimetallic surface alloys, open up new possibilities in
      selective and dynamical engineering of alloy surfaces for catalysis.

PMID- 19166292
TI  - Using marine natural products to discover a protease that catalyzes peptide
      macrocyclization of diverse substrates.
AB  - Small N-C terminally cyclic ribosomal peptides are common in nature, yet the
      mechanisms underlying their biosyntheses remain largely unknown. We recently
      identified candidate peptide cyclase genes in the metagenomes of marine animals.
      Here we report that PatG, a protease discovered in this analysis, cleaves
      variables, short peptides out of a precursor protein, and cyclizes these peptides
      in vivo and in vitro.

PMID- 19166293
TI  - Influence of germination with different selenium solutions on nutritional value
      and cytotoxicity of lupin seeds.
AB  - The effect of different selenium solutions during germination of lupin seeds
      (Lupinus angustifolius L. cv. Zapaton) on the content of total selenium, protein,
      amino acids, soluble carbohydrates, total antioxidant activity, and cytotoxicity
      on HL-60 human leukemic cell line has been studied. Seeds were germinated in the
      presence of selenite (Na2SeO3) or selenate (Na2SeO4) solutions at different
      concentrations (0, 2, 4, 6, and 8 mg/L) for 5 days at either 20 or 25 degrees C.
      The addition of inorganic Se forms significantly increased Se content in lupin
      sprouts in a dose-dependent manner. The highest Se content in lupin sprouts was
      observed when germination was carried out with selenate solutions at 20 degrees C
      (11 microg/g of dw) or 25 degrees C (14 microg/g of dw). The Se-enriched sprouts
      presented an improvement in antioxidant activity (up to 117.8 and 103.5 micromol
      of Trolox/g of dw) as well as in essential amino acid content, and no
      cytotoxicity was observed on HL-60 human leukemic cells. Lupin seeds germinated
      with 8 mg/L selenate solutions for 5 days at 20 degrees C exhibited a higher
      germination rate (>90%) and a higher concentration of some essential amino acids
      than those obtained in selenite solutions in the same germination conditions.
      Therefore, the employment of selenate solutions at a concentration of 8 mg/L and
      germination for 5 days at 20 degrees C may be suggested for the production of Se
      enriched lupin sprouts.

PMID- 19166294
TI  - Nickel-mediated three-component cycloaddition reaction of carboryne, alkenes, and
      alkynes.
AB  - Transition metal mediated multicomponent cross-coupling reactions are a powerful
      strategy to assemble complex molecules from very simple precursors in a single
      operation. This Communication reports a nickel-mediated three-component
      cycloaddition reaction of carboryne with alkenes and alkynes giving
      dihydrobenzocarborane derivatives with excellent chemo- and regioselectivity. A
      reaction mechanism involving sequential alkene and alkyne insertion, followed by
      reductive elimination, is proposed. The key intermediate of nickelacyclopentane
      was isolated and confirmed by single-crystal X-ray analyses. This work furnishes
      a new method for the preparation of substituted dihydrobenzocarboranes that are
      difficult to obtain by other methods.

PMID- 19166295
TI  - Influence of specific fatty acids on the asymmetric distribution of saturated
      fatty acids in sunflower (Helianthus annuus L.) triacylglycerols.
AB  - The 1,3-random-2-random theory was proposed several years ago to explain the
      fatty acid distribution in vegetable oil triacylglycerols. However, by
      demonstrating an asymmetry between positions sn-1 and sn-3 in olive oil, cocoa
      butter, sunflower oil, etc., a number of studies have shown that this theory does
      not hold true for some oils and fatty acids. Accordingly, the distribution of
      fatty acids in sunflower triacylglycerols has been studied, calculating the alpha
      coefficient of asymmetry in several combinations of standard linoleic, high
      oleic, and high-stearic sunflower oils. The results obtained from the oils of
      these lines and from single seed oil samples indicate that the asymmetry for
      saturated fatty acids is greater in high-oleic than in standard linoleic
      backgrounds. Hence, the distribution of the fatty acids within the
      triacylglycerol molecule appears to depend not only on the fatty acid under study
      but also on the other fatty acids in the oil. Thus, it is demonstrated for the
      first time that certain fatty acids can influence the distribution of other fatty
      acids within triacylglycerols.

PMID- 19166296
TI  - Redox actuation of a microcantilever driven by a self-assembled
      ferrocenylundecanethiolate monolayer: an investigation of the origin of the
      micromechanical motion and surface stress.
AB  - The electrochemically induced motion of free-standing microcantilevers is
      attracting interest as micro/nanoactuators and robotic devices. The development
      and implementation of these cantilever-based actuating technologies requires a
      molecular-level understanding of the origin of the surface stress that causes the
      cantilever to bend. Here, we report a detailed study of the electroactuation
      dynamics of gold-coated microcantilevers modified with a model, redox-active
      ferrocenylundecanethiolate self-assembled monolayer (FcC(11)SAu SAM). The
      microcantilever transducer enabled the observation of the redox transformation of
      the surface-confined ferrocene. Oxidation of the FcC(11)SAu SAM in perchlorate
      electrolyte generated a compressive surface stress change of -0.20 +/- 0.04 N m(
      1), and cantilever deflections ranging from approximately 0.8 microm to
      approximately 60 nm for spring constants between approximately 0.01 and
      approximately 0.8 N m(-1). A comparison of the charge-normalized surface stress
      of the FcC(11)SAu cantilever with values published for the electrochemical
      oxidation of polyaniline- and polypyrrole-coated cantilevers reveals a striking
      10- to 100-fold greater stress for the monomolecular FcC(11)SAu system compared
      to the conducting polymer multilayers used for electroactuation. The larger
      stress change observed for the FcC(11)SAu microcantilever is attributable to
      steric constraints in the close-packed FcC(11)SAu SAM and an efficient coupling
      between the chemisorbed FcC(11)S- monolayer and the Au-coated microcantilever
      transducer (vs physisorbed conducting polymers). The microcantilever deflection
      vs quantity of electrogenerated ferrocenium obtained in cyclic voltammetry and
      potential step/hold experiments, as well as the surface stress changes obtained
      for mixed FcC(11)S-/C(11)SAu SAMs containing different populations of clustered
      vs isolated ferrocenes, have permitted us to establish the molecular basis of
      stress generation. Our results strongly suggest that the redox-induced deflection
      of a FcC(11)SAu microcantilever is caused by a monolayer volume expansion
      resulting from collective reorientational motions induced by the complexation of
      perchlorate ions to the surface-immobilized ferroceniums. The cantilever responds
      to the lateral pressure exerted by an ensemble of reorienting ferrocenium-bearing
      alkylthiolates upon each other rather than individual anion pairing events. This
      finding has general implications for using SAM-modified microcantilevers as
      (bio)sensors because it indicates that the cantilever responds to collective in
      plane molecular interactions rather than reporting individual (bio)chemical
      events.

PMID- 19166297
TI  - Influence of heat on biological activity and concentration of oleocanthal--a
      natural anti-inflammatory agent in virgin olive oil.
AB  - The olive oil phenolic oleocanthal is a natural nonsteroidal anti-inflammatory
      compound that irritates the oral pharynx in a dose-dependent manner. It has been
      proposed that the biological activity of oleocanthal is partially responsible for
      the beneficial health effects of the Mediterranean diet. Virgin olive oil
      containing oleocanthal is often added as an ingredient in a number of cooked
      dishes, and therefore it is of great importance to understand how best to
      preserve the putative health-promoting benefits of this compound, as olive oil
      phenolics are subject to degradation upon heating in general. One extra virgin
      olive oil containing 53.9 mg/kg oleocanthal was heated at various temperatures
      (100, 170, and 240 degrees C) for set time periods (0, 1, 5, 20, 60, and 90 min).
      Oleocanthal concentrations were quantified using HPLC, and its biological
      activity was determined with a taste bioassay measuring the intensity of throat
      irritation. Results demonstrated that oleocanthal was heat stable compared with
      other olive oil phenolics, with a maximum loss of 16% as determined by HPLC
      analysis. However, there was a significant decrease of up to 31% (p < 0.05) in
      the biological activity of oleocanthal as determined by the taste bioassay.
      Although there was minimal degradation of oleocanthal concentration, there was a
      significant decrease in the biological activity of oleocanthal upon extended
      heating time, indicating a possible loss of the putative health -benefiting
      properties of oleocanthal. Alternatively, the difference in the concentration and
      biological activity of oleocanthal after heat treatment could be a result of an
      oleocanthal antagonist forming, decreasing or masking the biological activity of
      oleocanthal.

PMID- 19166298
TI  - Bioavailability of anthocyanins from purple carrot juice: effects of acylation
      and plant matrix.
AB  - Absorption of cyanidin-based anthocyanins is not fully understood with respect to
      dose or anthocyanin structure. In feeding studies using whole foods, nonacylated
      anthocyanins are more bioavailable than their acylated counterparts, but the
      extent to which plant matrix determines relative bioavailability of anthocyanins
      is unknown. Using juice of purple carrots to circumvent matrix effects, a feeding
      trial was conducted to determine relative bioavailability of acylated and
      nonacylated anthocyanins and to assess dose-response effects. Appearance of
      anthocyanins in plasma was measured in 10 healthy adults for 8 h following
      consumption of purple carrot juice. Each subject consumed 50, 150, and 250 mL of
      juice containing 76 micromol (65 mg), 228 micromol (194 mg), and 380 micromol
      (323 mg) of total anthocyanins, respectively. Acylated anthocyanins comprised 76%
      of total anthocyanins in the juice, yet their bioavailability was found to be
      significantly less than that of nonacylated anthocyanins. Peak plasma
      concentrations of nonacylated anthocyanins were 4-fold higher than that for
      acylated anthocyanins. Absorption efficiency declined across the doses
      administered. Because the treatments were consumed as juice, it could be
      discerned that the difference in bioavailability of acylated versus nonacylated
      anthocyanins was not primarily caused by interactions with the plant matrix.

PMID- 19166299
TI  - Lateral proton transfer between the membrane and a membrane protein.
AB  - Proton transport across biological membranes is a key step of the energy
      conservation machinery in living organisms, and it has been proposed that the
      membrane itself plays an important role in this process. In the present study we
      have investigated the effect of incorporation of a proton transporter, cytochrome
      c oxidase, into a membrane on the protonation kinetics of a fluorescent pH
      sensitive probe attached at the surface of the protein. The results show that
      proton transfer to the probe was slightly accelerated upon attachment at the
      protein surface (approximately 7 x 1010 s(-1) M(-1), compared to the expected
      value of (1-2) x 10(10) s(-1) M(-1)), which is presumably due to the presence of
      acidic/His groups in the vicinity. Upon incorporation of the protein into small
      unilamellar phospholipid vesicles the rate increased by more than a factor of 400
      to approximately 3 x 10(13) s(-1) M(-1), which indicates that the protein
      attached probe is in rapid protonic contact with the membrane surface. The
      results indicate that the membrane acts to accelerate proton uptake by the
      membrane-bound proton transporter.

PMID- 19166300
TI  - Enterococcus faecalis strains differentially regulate Alix/AIP1 protein
      expression and ERK 1/2 activation in intestinal epithelial cells in the context
      of chronic experimental colitis.
AB  - Monoassociation of germfree Interleukin 10 gene deficient (IL-10-/-) 129SvEv but
      not wild-type mice with Enterococcus faecalis induces severe chronic colitis.
      Bacterial strain-specific effects on the development of chronic intestinal
      inflammation are not understood. We investigated the molecular mechanisms of E.
      faecalis OG1RF (human clinical isolate, colitogenic) and E. faecalis ms2
      (endogenous isolate from an IL-10-/- mouse) in initiating chronic experimental
      colitis using IL-10-/- mice. Monoassociation of IL-10-/- mice for 14 weeks
      revealed significant differences in colonic inflammation (3.6 +/- 0.2 and 2.4 +/-
      0.6 for OG1RF and ms2, respectively) (n = 5 mice in each group) (histological
      scoring (0-4)). Consistent with the tissue pathology, gene expression of the pro
      inflammatory chemokine interferon-gamma inducible protein-10 (IP-10) was
      significantly higher in intestinal epithelial cells (IEC) derived from E.
      faecalis OG1RF monoassociated IL-10-/- mice. We further compared the
      differentially E. faecalis induced colitis on the epithelial level by 2D-SDS PAGE
      coupled with MALDI-TOF MS. Proteome analysis identified 13 proteins which were
      differentially regulated during disease progression in the epithelium of E.
      faecalis-monoassociated IL-10-/- mice. Regulation of Alix/AIP1 protein expression
      and ERK1/2 phosphorylation was validated in primary IEC and epithelial cell
      lines, suggesting a protective role for Alix/AIP1 in the process of disease
      progression. Alix/AIP1 protein expression was further characterized in epithelial
      cell lines using siRNA-mediated knock-down. Our study demonstrates E. faecalis
      strain-specific induction of colitis in IL-10-/- mice after 14 weeks of
      monoassociation. Our study suggests that Alix/AIP1 protein expression and ERK1/2
      activation are decreased in severe colitis.

PMID- 19166302
TI  - Dendrimer diffusion in kappa-carrageenan gel structures.
AB  - The effect of the kappa-carrageenan concentration on gel microstructure and self
      diffusion of polyamideamine dendrimers has been determined by transmission
      electron microscopy (TEM), image analysis, and nuclear magnetic resonance (NMR)
      diffusometry. Different salt conditions of KCl, NaCl, and mixtures thereof
      allowed for formation of significantly different microstructures. The kappa
      carrageenan concentrations were varied between 0.25 and 3.0 w/w% for a salt
      mixture containing 20 mM KCl and 200 mM NaCl gels and between 0.5 and 4.0 w/w%
      for 250 mM NaCl gels. Furthermore, the effect of potassium ion concentration on
      the gel structure and the dendrimer diffusion rate was determined. The potassium
      ion concentration was varied between 20 mM KCl and 200 mM KCl. Two different
      dendrimer generations with significant difference in size were used: G2 and G6.
      Dendrimers were found to be sensitive probes for determination of the effect of
      the gel microstructure on molecular diffusion rate. A qualitative comparison
      between TEM micrographs, NMR diffusometry data and image analysis showed that the
      gel structure has a large impact on the dendrimers diffusion in kappa-carrageenan
      gels. It was found that diffusion was strongly influenced by the kappa
      carrageenan concentration and the dendrimer generation. Small voids in the gel
      network gave strongly reduced diffusion. Image analysis revealed that the
      interfacial area between the gel network and the surrounding water phase
      correlated well with the dendrimer diffusion.

PMID- 19166301
TI  - Insight into the sialome of the Black Fly, Simulium vittatum.
AB  - Adaptation to vertebrate blood feeding includes development of a salivary "magic
      potion" that can disarm host hemostasis and inflammatory reactions. Within the
      lower Diptera, a vertebrate blood-sucking mode evolved in the Psychodidae (sand
      flies), Culicidae (mosquitoes), Ceratopogonidae (biting midges), Simuliidae
      (black flies), and the frog-feeding Corethrellidae. Sialotranscriptome analyses
      from several species of mosquitoes and sand flies and from one biting midge
      indicate divergence in the evolution of the blood-sucking salivary potion,
      manifested in the finding of many unique proteins within each insect family, and
      even genus. Gene duplication and divergence events are highly prevalent, possibly
      driven by vertebrate host immune pressure. Within this framework, we describe the
      sialome (from Greek sialo, saliva) of the black fly Simulium vittatum and discuss
      the findings within the context of the protein families found in other blood
      sucking Diptera. Sequences and results of Blast searches against several protein
      family databases are given in Supplemental Tables S1 and S2, which can be
      obtained from http://exon.niaid.nih.gov/transcriptome/S_vittatum/T1/SV-tb1.zip
      and http://exon.niaid.nih.gov/transcriptome/S_vittatum/T2/SV-tb2.zip .

PMID- 19166303
TI  - Tyrosinase inhibitory polyphenols from roots of Morus lhou.
AB  - Twelve polyphenols (1-12) possessing tyrosinase inhibitory properties were
      isolated from the methanol (95%) extract of Morus lhou. The isolated compounds
      consisted of four flavanones (1-4), four flavones (5-8), and four
      phenylbenzofuranes (9-12). Moracin derivative 12 proved to be new a compound
      which was fully characterized. Compounds 1-12 were evaluated for both
      monophenolase and diphenolase (the two steps catalyzed by tyrosinase) inhibition
      to identify the structural characteristics required for mushroom tyrosinase
      inhibition. We observed that all parent compounds (1, 5, and 9) possessing an
      unsubstituted resorcinol group were highly effective inhibitors of monophenolase
      activity (IC(50) values of 1.3, 1.2, and 7.4 microM). The potency of the
      inhibitors diminished with alkyl substitution on either the aromatic ring or the
      hydroxyl functions. Interestingly, flavone 5 was shown to possess only
      monophenolase inhibitory activity, but flavanone 1 and phenylbenzofuran 9
      inhibited diphenolase as well as monophenolase significantly. The inhibitory mode
      of these species was also dependent upon the skeleton: phenylbenzofuran 9
      manifested a simple competitive inhibition mode for monophenolase and
      diphenolase; on the other hand flavanone 1 (monophenolase, k(3) = 0.1966 min(-1)
      microM(-1), k(4) = 0.0082 min(-1), and K(i)(app) = 0.0468 microM; diphenolase,
      k(3) = 0.0014 min(-1) microM(-1), k(4) = 0.0013 min(-1), and K(i)(app) = 0.8996
      microM) and flavone 5 both showed time-dependent inhibition against
      monophenolase. Compound 1 operated according to the simple reversible slow
      binding model whereas compound 5 operated under the enzyme isomerization model.

PMID- 19166304
TI  - Swelling of a microgel with immobilized carbon nanotubes in an ionic liquid.
AB  - We use a Flory-Huggins type approach to describe the swelling of a polymer
      microgel (a finite size network of polymer chains covalently bound with each
      other) with immobilized carbon nanotubes in an ionic liquid. The ionic liquid is
      modeled as a "two-component" solvent consisting of anions and cations. The anions
      and cations are assumed to have different affinities to the microgel. It is
      supposed that the carbon nanotubes form a conducting cluster interpenetrating the
      microgel. We show that if the difference of the Flory-Huggins parameters
      describing affinities of the anions and the cations to the microgel is high
      enough, the swelling ratio of the gel can depend on its size. The physical reason
      for the phenomenon is the violation of the cations and anions concentrations
      equality inside the gel that causes a shift of the free energy and can lead to a
      swelling-collapse transition. The segregation of cations and anions is different
      for microgels having different sizes because it is opposed by electrostatic
      field.

PMID- 19166305
TI  - What a difference a 5f element makes: trivalent and tetravalent uranium halide
      complexes supported by one and two bis[2-(diisopropylphosphino)-4
      methylphenyl]amido (PNP) ligands.
AB  - The coordination behavior of the bis[2-(diisopropylphosphino)-4
      methylphenyl]amido ligand (PNP) toward UI3(THF)4 and UCl4 has been investigated
      to access new uranium(III) and uranium(IV) halide complexes supported by one and
      two PNP ligands. The reaction between (PNP)K (6) and 1 equiv of UI3(THF)4
      afforded the trivalent halide complex (PNP)UI2(4-tBu-pyridine)2 (7) in the
      presence of 4-tert-butylpyridine. The same reaction carried out with UCl4 and no
      donor ligand gave [(PNP)UCl3]2 (8), in which the uranium coordination sphere in
      the (PNP)UCl3 unit is completed by a bridging chloride ligand. When UCl4 is
      reacted with 1 equiv (PNP)K (6) in the presence of THF, trimethylphosphine oxide
      (TMPO), or triphenylphosphineoxide (TPPO), the tetravalent halide complexes
      (PNP)UCl3(THF) (9), (PNP)UCl3(TMPO)2 (10), and (PNP)UCl3(TPPO) (11),
      respectively, are formed in excellent yields. The bis(PNP) complexes of
      uranium(III), (PNP)2UI (12), and uranium(IV), (PNP)2UCl2 (13), were easily
      isolated from the analogous reactions between 2 equiv of 6 and UI3(THF)4 or UCl4,
      respectively. Complexes 12 and 13 represent the first examples of complexes
      featuring two PNP ligands coordinated to a single metal center. Complexes 7-13
      have been characterized by single-crystal X-ray diffraction and 1H and 31P NMR
      spectroscopy. The X-ray structures demonstrate the ability of the PNP ligand to
      adopt new coordination modes upon coordination to uranium. The PNP ligand can
      adopt both pseudo-meridional and pseudo-facial geometries when it is kappa3
      (P,N,P) coordinated, depending on the steric demand at the uranium metal center.
      Additionally, its hemilabile character was demonstrated with an unusual kappa2
      (P,N) coordination mode that is maintained in both the solid-state and in
      solution. Comparison of the structures of the mono(PNP) and bis(PNP) complexes 7,
      9, 11-13 with their respective C5Me5 analogues 1-4 undoubtedly show that a more
      sterically congested environment is provided by the PNP ligand. The electronic
      influence of replacing the C5Me5 ligands with PNP was investigated using
      electronic absorption spectroscopy and electrochemistry. For 12 and 13, a
      chemically reversible wave corresponding to the UIV/UIII redox transformation
      comparable to that for 3 and 4 was observed. However, a 350 mV shift of this
      couple to more negative potentials was observed on substitution of the bis(C5Me5)
      by the bis(PNP) framework, therefore pointing to a greater electronic density at
      the metal center in the PNP complexes. The UV-visible region of the electronic
      spectra for the mono(PNP) and bis(PNP) complexes appear to be dominated by PNP
      ligand-based transitions that are shifted to higher energy in the uranium
      complexes than in the simple ligand anion (6) spectrum, for both the UVI and UIII
      oxidation states. The near IR region in complexes 1-4 and 7, 9, 11-13 is
      dominated by f-f transitions derived from the 5f3 and 5f2 valence electronic
      configuration of the metal center. Though complexes of both ligand sets exhibit
      similar intensities in their f-f bands, a somewhat larger ligand-field splitting
      was observed for the PNP system, consistent with its higher electron donating
      ability.

PMID- 19166307
TI  - Crystal and molecular structure of (2,9-dimethyl-1,10
      phenanthroline)(glycylglycinato)copper(II) pentahydrate.

PMID- 19166306
TI  - Substrate binding preferences and pka determinations of a nitrile hydratase model
      complex: variable solvent coordination to [(bmmp-TASN)Fe]OTf.
AB  - The five-coordinate iron-dithiolate complex (N,N'-4,7-bis-(2'-methyl-2'
      mercatopropyl)-1-thia-4,7-diazacyclononane)iron(III), [LFe]+, has been isolated
      as the triflate salt from reaction of the previously reported LFeCl with thallium
      triflate. Spectroscopic characterization confirms an S = 1/2 ground state in non
      coordinating solvents with room temperature microeff = 1.78 microB and electron
      paramagnetic resonance (EPR) derived g-values of g1 = 2.04, g2 = 2.02 and g3 =
      2.01. [LFe]+ binds a variety of coordinating solvents resulting in six-coordinate
      complexes [LFe-solvent]+. In acetonitrile the low-spin [LFe-NCMe]+ (g1 = 2.27, g2
      = 2.18, and g3 = 1.98) is in equilibrium with [LFe]+ with a binding constant of
      Keq = 4.7 at room temperature. Binding of H2O, DMF, methanol, DMSO, and pyridine
      to [LFe]+ yields high-spin six-coordinate complexes with EPR spectra that display
      significant strain in the rhombic zero-field splitting term E/D. Addition of 1
      equiv of triflic acid to the previously reported diiron species (LFe)2O results
      in the formation of [(LFe)2OH]OTf, which has been characterized by X-ray
      crystallography. The aqueous chemistry of [LFe]+ reveals three distinct species
      as a function of pH: [LFe-OH2]+, [(LFe)2OH]OTf, and (LFe)2O. The pKa values for
      [LFe-OH2]+ and [(LFe)2OH]OTf are 5.4 +/- 0.1 and 6.52 +/- 0.05, respectively.

PMID- 19166308
TI  - A 13C and 15N solid-state NMR study of structural disorder and aurophilic bonding
      in AuI and AuIII cyanide complexes.
AB  - Solid-state nuclear magnetic resonance has been used to study several
      cyanoaurates. Carbon-13 and nitrogen-15 NMR spectra of samples enriched with
      isotopically labeled 13C,15N cyanide ligands were recorded for stationary samples
      and samples spinning at the magic angle. Several salts of the dicyanoaurate(I)
      anion, M[Au(CN)2], where M = n-butylammonium, potassium, and thallium, were
      studied via solid-state NMR. A gold(III) cyanide, K[Au(CN)4], was also
      investigated. Carbon-13 and nitrogen-15 chemical shift tensors are reported for
      each salt, as are the measured 13C,15N direct dipolar coupling constants together
      with the related derived cyanide bond lengths, r(C,N). The value for r(C,N) in
      [(n-C4H9)4N][Au(CN)2], 1.17(5) A, was determined to be more realistic than a
      previously reported X-ray diffraction value of 1.03(4) A. Large 13C NMR line
      widths from Tl[Au(CN)2], 250-315 Hz, are attributed to coupling with 197Au (I =
      3/2) and/or 203/205Tl (I = 1/2), as confirmed by measurements of the transverse
      relaxation constant, T2. Investigation of the carbon-13 chemical shifts for
      cyanide ligands bound to gold involved in a variety of metallophilic bonding
      environments demonstrates that the chemical shift is sensitive to metallophilic
      bonding. Differences in Au-Tl metallophilic bonding are shown to cause a
      difference in the isotropic carbon-13 chemical shift of up to 15.7 ppm, while
      differences in Au-Au aurophilic bonding are found to be responsible for a change
      of up to 5.9 ppm. The disordered polymeric material gold(I) monocyanide, AuCN,
      was also investigated using 13C and 15N SSNMR. Two-dimensional 13C,13C double
      quantum dipolar-recoupling spectroscopy was used to probe connectivity in this
      material. The 13C NMR site multiplicity in AuCN is explained on the basis of
      sensitivity of the carbon-13 chemical shift to aurophilic bonding of the directly
      bonded gold atom. This assignment allows estimation of the position of the linear
      [-M-CN-]infinity chain's position with respect to the neighboring polymer chain.
      For the samples studied, a range of 7 +/- 2% to 25 +/- 5% of the AuCN chains are
      found to be "slipped" instead of aligned with the neighboring chains at the metal
      position.

PMID- 19166309
TI  - Electron diffraction study of bis(pentafluorosulfur), bis(pentafluoroselenium),
      and bis(pentafluorotellurium) oxides.

PMID- 19166311
TI  - Redox regulation of SH2-domain-containing protein tyrosine phosphatases by two
      backdoor cysteines.
AB  - Protein tyrosine phosphatases (PTPs) are known to be regulated by
      phosphorylation, localization, and protein-protein interactions. More recently,
      redox-dependent inactivation has emerged as a critical factor in attenuating PTP
      activity in response to cellular stimuli. The tandem Src homology 2 domain
      containing PTPs (SHPs) belong to the family of nonreceptor PTPs whose activity
      can be modulated by reversible oxidation in vivo. Herein we have investigated in
      vitro the kinetic and mechanistic details of reversible oxidation of SHP-1 and
      SHP-2. We have confirmed the susceptibility of the active site cysteines of SHPs
      to oxidative inactivation, with rate constants for oxidation similar to other
      PTPs (2-10 M(-1) s(-1)). Both SHP-1 and SHP-2 can be reduced and reactivated with
      the reductants DTT and gluthathione, whereas only the catalytic domain of SHP-2
      is subject to reactivation by thioredoxin. Stabilization of the reversible
      oxidation state of the SHPs proceeds via a novel mechanism unlike for other PTPs
      wherein oxidation yields either a disulfide between the catalytic cysteine and a
      nearby "backdoor" cysteine or a sulfenylamide bond with the amide backbone
      nitrogen of the adjacent amino acid. Instead, in the reversibly oxidized and
      inactivated SHPs, the catalytic cysteine is rereduced while two conserved
      backdoor cysteines form an intramolecular disulfide. Formation of this backdoor
      backdoor disulfide is dependent on the presence of the active site cysteine and
      can proceed via either active site cysteine-backdoor cysteine intermediate.
      Removal of both backdoor cysteines leads to irreversible oxidative inactivation,
      demonstrating that these two cysteines are necessary and sufficient for ensuring
      reversible oxidation of the SHPs. Our results extend the mechanisms by which
      redox regulation of PTPs is used to modulate intracellular signaling pathways.

PMID- 19166312
TI  - Biochemical characterization of dithiol glutaredoxin 8 from Saccharomyces
      cerevisiae: the catalytic redox mechanism redux.
AB  - Two dithiol glutaredoxins (Grxs), Grx1 and Grx2, from yeast have been
      characterized to date. A third putative dithiol glutaredoxin-encoding gene (GRX8)
      has been identified in silico. Here we show that deletion of GRX8 does not result
      in a reduced growth rate under oxidative stress conditions, nor does it enhance
      the defects of Deltagrx1 and Deltagrx2 single or double mutants. We furthermore
      compare the enzymatic properties of recombinant ScGrx8 with the monothiol
      glutaredoxin ScGrx7. Molecular models of ScGrx8 suggest that the protein has a
      canonical Grx fold, a significantly altered substrate binding site, and a Trp14
      type cysteine motif at the catalytic center. ScGrx8 did not bind heavy metal ions
      and was exclusively monomeric. Apparent k(cat) values for ScGrx8 in the standard
      enzymatic assay were about 3 orders of magnitude less than for ScGrx7, whereas
      apparent K(m) values were comparable. Mass spectrometric analyses support a ping
      pong mechanism for ScGrx7 and ScGrx8 with a glutathionylated protein as an
      intermediate. Reduction kinetics of ScGrx8 disulfide, glutathionylated
      ScGrx8(C28S), and glutathionylated ScGrx7 revealed significant differences
      between the proteins. Surprisingly, mutation of the more C-terminal cysteine
      residue in the CPDC motif of ScGrx8 also abolished the slight enzymatic activity,
      and thus the standard catalytic mechanism for glutathionylated substrates does
      not apply to the enzyme. In summary, ScGrx8 has several novel structural and
      mechanistic features expanding the subclasses of glutaredoxins. A refined
      catalytic model for monothiol and dithiol glutaredoxins is presented explaining
      the diversity of enzymatic activities in vitro and pointing to different
      functions in vivo.

PMID- 19166314
TI  - Structural tungsten-imido chemistry: the gas-phase structure of W(NBut)2(NHBut)2
      and the solid-state structures of novel heterobimetallic W/N/M (M = Rh, Pd, Zn)
      species.
AB  - The gas-phase (electron diffraction) and solid-state (X-ray) structures of
      W(NBut)2(NHBut)2 (1) have been determined. In the gas phase, 1 adopts both C1 and
      C2 conformations in a 69:31 ratio. The solid-state structure is disordered over
      two equal sites, both showing approximate C2 conformation as in the gas phase;
      the imido and amido centers are, however, clearly distinguished. Compound 1 has
      been used to synthesize novel heterobimetallic derivatives W(NBut)4[Rh(COD)]2 (3)
      and W(NBut)4[Pd(eta3-C3H5)]2 (4) via the dilithiated intermediate Li2[W(NBut)4]
      (2). In both cases, the [W(NBut)4] moiety bridges the two organometallic
      fragments. Reaction of 1 with Me2Zn has produced [Me(tBuN)W(mu
      NBut)2ZnMe(NH2But)] (5). The structures of 3, 4, and 5 have been determined.
      Thermal decomposition of 4 under an autogenerated pressure at 700 degrees C has
      formed the hitherto uncharacterized bimetallic alloy WPd2.

PMID- 19166313
TI  - Two distinct motifs within the p53 transactivation domain bind to the Taz2 domain
      of p300 and are differentially affected by phosphorylation.
AB  - The tumor suppressor p53 functions as a transcriptional activator for many genes,
      including several key genes involved in cell cycle arrest and apoptosis.
      Following DNA damage-induced stress, p53 undergoes extensive posttranslational
      modification, resulting in increased stability and activity. Two critical
      cofactors for p53-mediated transactivation are the histone acetyltransferase
      paralogues CREB-binding protein (CBP) and p300. The N-terminal transactivation
      domain of p53 interacts with several domains of CBP/p300, including the Taz2
      domain. Here, we report the effects of specific p53 phosphorylations on its
      interaction with the Taz2 domain of p300. Using a competitive fluorescence
      anisotropy assay, we determined that monophosphorylation of p53 at Ser(15) or
      Thr(18) increased the affinity of p53(1-39) for Taz2, and diphosphorylations at
      Ser(15) and Ser(37) or Thr(18) and Ser(20) further increased the affinity. In
      addition, we identified a second binding site for Taz2 within p53 residues 35-59.
      This second site bound Taz2 with a similar affinity as the first site, but the
      binding was unaffected by phosphorylation. Thus, p53 posttranslational
      modification modulates only one of the two binding sites for p300 Taz2. Further
      investigation of Taz2 binding to p53(1-39) or p53(35-59) by isothermal titration
      calorimetry indicated that upon complex formation, the change in heat capacity at
      constant pressure, DeltaC(p), was negative for both sites, suggesting the
      importance of hydrophobic interactions. However, the more negative value of
      DeltaC(p) for Taz2 binding to the first (-330 cal/(mol.K)) compared to the second
      site (-234 cal/(mol.K)) suggests that the importance of nonpolar and polar
      interactions differs between the two sites.

PMID- 19166315
TI  - Cyclopentadienylidene. A matrix isolation study exploiting photolysis with
      unpolarized and plane-polarized light.
AB  - Diazocyclopentadiene (1) was photolyzed in N(2), CO, and other low-temperature
      matrices. The resulting carbene, cyclopentadienylidene (2), was characterized by
      its UV and IR spectra, and its thermal dimerization and reaction with CO were
      observed. Photolysis of 1 with plane-polarized light gave matrices exhibiting
      linear dichroism. Comparison of dichroic IR and UV spectra revealed that the
      photolysis proceeds via an excited A(l) state of the diazo compound. Plane
      polarized irradiation of the corresponding ketene (4) in CO matrices resulted in
      photoreorientation of the molecules of 4 without significant loss.

PMID- 19166316
TI  - Free radical addition of butanethiol to vegetable oil double bonds.
AB  - Butanethiol was used in ultraviolet-initiated thiol-ene reaction with canola and
      corn oils to produce sulfide-modified vegetable oils (SMVO). The crude SMVO
      product was successfully purified by solvent extraction, vacuum evaporation, and
      silica gel chromatography. The SMVO products were characterized by nuclear
      magnetic resonance and Fourier transform infrared spectroscopy. Further product
      characterization and analysis was conducted using GC and GC-MS on the fatty acid
      methyl esters obtained by the transesterification of the SMVO products.
      Investigation of the effect of reaction conditions showed that high yield and
      high conversion of double bonds into thiol were favored at low reaction
      temperatures and high butanethiol/vegetable oil ratios. Canola and corn oils gave
      similar double-bond conversions and yields of the desired SMVO product even
      though they have big differences in the relative numbers of single and multiple
      double bonds in their structures. Under best reaction conditions, up to 97% of
      double-bond conversion and 61% isolated yields of the purified SMVO products were
      attained.

PMID- 19166317
TI  - Changes in some carotenoids and apocarotenoids during flower development in
      Boronia megastigma (Nees).
AB  - The carotenoid profile of an acetone extract from the flowers and leaves of
      Boronia megastigma (Nees) was examined. A comparison was made of the major
      carotenoids found in boronia flowers and leaves. The C-40 carotenoids beta
      carotene, zeaxanthin, lutein, and neoxanthin were positively identified in
      boronia flowers using known standards, UV-vis spectra, and mass spectrometry. Two
      other carotenoids were tentatively assigned as the palmitic acid ester of 3
      hydroxy-10'-apocaroten-10'-oic acid and 9,15,9'-tri-cis-zeta-carotene.
      Additionally, changes in the levels of C-40 carotenoids, C-27 apocarotenoids, and
      beta-ionone during flower development were measured. Significant increases in
      beta-carotene and apocarotenoids that could be derived from cleavage in the 9,10
      position, including beta-ionone and various C-27 apocarotenoids, were observed at
      the time of flower opening. An increase in lutein, which is derived through an
      alternative biosynthetic pathway, was not observed during flower opening, thus
      indicating the possibility that the beta-carotene pathway was activated during
      flower opening in boronia. The understanding of these processes may assist in
      optimizing harvest and postharvest processes useful to the boronia extraction
      industry.

PMID- 19166319
TI  - Two aspartic proteinases secreted by the pathogenic yeast Candida parapsilosis
      differ in expression pattern and catalytic properties.
AB  - Secreted aspartic proteinases (Sap) play a role in the virulence of pathogenic
      Candida spp. Candida parapsilosis possesses three genes encoding these enzymes:
      SAPP1, SAPP2, and SAPP3. We analyzed the expression of the SAPP1 and SAPP2 genes
      and the production of Sapp1p and Sapp2p proteinases in the presence of different
      nitrogen sources. While the SAPP2 transcript was present under all of the
      conditions tested, expression of SAPP1 was induced only by the presence of
      exogenous protein as the sole nitrogen source. The concentration of Sapp1 p in
      the medium upon induction was at least one order of magnitude higher than the
      concentration of Sapp2p in all media tested in this study. Enzymological
      characterization of purified Sapp1 p and Sapp2p demonstrated that Sapp2p has a
      more restricted substrate specificity and significantly lower catalytic activity
      than Sapp1p. Homology models of Sapp1p and Sapp2p revealed structural motifs that
      may be responsible for the differences between these two enzymes. Our results
      indicate that C. parapsilosis secretes a low level of Sapp2p proteinase with
      narrow substrate specificity and low proteolytic activity under most conditions,
      while expression and secretion of a higher amount of catalytically efficient
      Sapp1p enzymes is triggered in the presence of exogenous protein serving as a
      nitrogen source.

PMID- 19166321
TI  - Co-expression of 9-O-acetylated sialoglycoproteins and their binding proteins on
      lymphoblasts of childhood acute lymphoblastic leukemia: an anti-apoptotic role.
AB  - Enhanced levels of 9-O-acetylated sialoglycoproteins (Neu5,9Ac(2)GPs) as disease
      associated molecules was reported to act as signaling molecules for promoting
      survival of lymphoblasts in childhood acute lymphoblastic leukemia (ALL). Here,
      we searched for potential physiological ligands for Neu5,9Ac(2)GPs that could be
      involved in modulating the survival of lymphoblasts. Accordingly, we examined the
      presence of binding proteins for Neu5,9Ac(2)GPs on cell lines and primary cells
      of patients with B- and T-ALL, at presentation of the disease. Peripheral blood
      mononuclear cells from normal healthy donors and cells from myeloid leukemia
      patients were used for comparison. Neu5,9Ac(2)GPs-binding proteins (BPs) were
      specifically detected on the surface of both T- and B-ALL-lymphoblasts and ALL
      cell lines along with the consistent presence of Neu5,9Ac(2)GPs. The
      Neu5,9Ac(2)GPs and BPs also co-localized on the cell surface and interacted
      specifically in vitro. Apoptosis of lymphoblasts, induced by serum starvation,
      was reversed in the presence of purified Neu5,9Ac(2)GPs due to possible
      engagement of BPs, and the anti-apoptotic role of this interaction was
      established. This is the first report of the presence of potential physiological
      ligands for disease-associated molecules like Neu5,9Ac(2)GPs, the interaction of
      which is able to trigger an anti-apoptotic signal conferring a survival advantage
      to leukemic cells in childhood ALL.

PMID- 19166320
TI  - Central nervous system: cholesterol turnover, brain development and
      neurodegeneration.
AB  - The average amount of cholesterol in the whole animal equals approximately 2100
      mg/kg body weight, and 15% and 23% of this sterol in the mouse and human,
      respectively, is found in the central nervous system. There is no detectable
      uptake across the blood-brain barrier of cholesterol carried in lipoproteins in
      the plasma, even in the newborn. However, high rates of de novo cholesterol
      synthesis in the glia and neurons provide the sterol necessary for early brain
      development. Once a stable brain size is achieved in the adult, cholesterol
      synthesis continues, albeit at a much lower rate, and this synthesis is just
      balanced by the excretion of an equal amount of sterol, either as 24(S)
      hydroxycholesterol or, presumably, as cholesterol itself.

PMID- 19166322
TI  - Structure-function relationship of the human antimicrobial peptide LL-37 and LL
      37 fragments in the modulation of TLR responses.
AB  - Cathelicidins are effector molecules of the innate host defense system that
      establish an antimicrobial barrier at epithelial interfaces. The human
      cathelicidin LL-37, in addition to its antimicrobial activity, also exhibits
      immunomodulatory effects, such as inhibition of pro-inflammatory responses to
      bacterial LPS in human monocytic cells. In this report, we demonstrate that LL-37
      almost completely prevents the pro-inflammatory cytokine release by human
      peripheral blood mononuclear cells (PBMCs) following stimulation with Toll-like
      receptor (TLR)4 and TLR2/1 agonists while leaving TLR2/6, TLR5, TLR7 and TLR8
      responses unchanged. Modulation of the TLR response by LL-37 occurred at least
      partly through the MAP kinase pathway via inhibition of p38 phosphorylation. By
      using an LL-37 library with overlapping sequences, we identified the mid-region
      of LL-37, comprising amino acids 13-31, as the active domain for the modulation
      of TLR responses. The mechanism of immunomodulation of LL-37 and LL-37 fragments
      is lipopoly-saccharide binding. Correlations between the capacity of LL-37
      fragments to modulate TLR responses and their physico-chemical properties
      revealed that cationicity and hydrophobicity are essential for the modulation of
      LL-37-mediated TLR responses.

PMID- 19166318
TI  - Glutathione dysregulation and the etiology and progression of human diseases.
AB  - Glutathione (GSH) plays an important role in a multitude of cellular processes,
      including cell differentiation, proliferation, and apoptosis, and as a result,
      disturbances in GSH homeostasis are implicated in the etiology and/or progression
      of a number of human diseases, including cancer, diseases of aging, cystic
      fibrosis, and cardiovascular, inflammatory, immune, metabolic, and
      neurodegenerative diseases. Owing to the pleiotropic effects of GSH on cell
      functions, it has been quite difficult to define the role of GSH in the onset
      and/or the expression of human diseases, although significant progress is being
      made. GSH levels, turnover rates, and/or oxidation state can be compromised by
      inherited or acquired defects in the enzymes, transporters, signaling molecules,
      or transcription factors that are involved in its homeostasis, or from exposure
      to reactive chemicals or metabolic intermediates. GSH deficiency or a decrease in
      the GSH/glutathione disulfide ratio manifests itself largely through an increased
      susceptibility to oxidative stress, and the resulting damage is thought to be
      involved in diseases, such as cancer, Parkinson's disease, and Alzheimer's
      disease. In addition, imbalances in GSH levels affect immune system function, and
      are thought to play a role in the aging process. Just as low intracellular GSH
      levels decrease cellular antioxidant capacity, elevated GSH levels generally
      increase antioxidant capacity and resistance to oxidative stress, and this is
      observed in many cancer cells. The higher GSH levels in some tumor cells are also
      typically associated with higher levels of GSH-related enzymes and transporters.
      Although neither the mechanism nor the implications of these changes are well
      defined, the high GSH content makes cancer cells chemoresistant, which is a major
      factor that limits drug treatment. The present report highlights and integrates
      the growing connections between imbalances in GSH homeostasis and a multitude of
      human diseases.

PMID- 19166323
TI  - Photosynthetic oxygen evolution is not reversed at high oxygen pressures:
      mechanistic consequences for the water-oxidizing complex.
AB  - We investigated the effects of elevated O(2) pressure on the production of O(2)
      by photosynthetic organisms in several species of plants, algae, and a
      cyanobacterium. Using a noninvasive fluorometry technique to monitor sequential
      turnover of the photosystem II (PSII) reaction center as a function of O(2)
      pressures, we showed that none of the reactions of water oxidation are affected
      by elevated O(2) pressures up to 50-fold greater than atmospheric conditions.
      Thus, the terminal step of O(2) release from the water oxidation complex (S(4) -
      > S(0) + O(2) + nH(+)) is not reversible in whole cells, leaves, or isolated
      thylakoid membranes containing PSII, in contrast to reports using detergent
      extracted PSII complexes. This implies that there is no thermodynamically
      accessible intermediate that can be populated by preventing or reversing the O(2)
      release step with O(2) at atmospheric pressure. To assess the sensitivity of PSII
      charge recombination to O(2) pressure, we quantitatively modeled the consequences
      of two putative perturbations to the catalytic cycle of water oxidation within
      the framework of the Kok model. On the basis of the breadth of oxygenic
      phototrophs examined in this study, we conclude that O(2) accumulation in cells
      or the atmosphere does not suppress photosynthetic productivity through the
      reversal of water oxidation in contemporary phototrophs and would have been
      unlikely to influence the evolution of oxygenic photosynthesis.

PMID- 19166324
TI  - High-resolution crystal structure of an artificial (betaalpha)(8)-barrel protein
      designed from identical half-barrels.
AB  - Ample evidence suggests that the ubiquitous (betaalpha)(8)-barrel enzyme fold has
      evolved by the duplication and fusion of an ancestral (betaalpha)(4)-half-barrel.
      To reconstruct this process in the laboratory with a model protein, we earlier
      fused two copies of the C-terminal half-barrel HisF-C of imidazole glycerol
      phosphate synthase (HisF) and stepwise stabilized the resulting HisF-CC
      construct. We now further increased its stability and solubility by introducing
      two additional amino acid exchanges, which allowed us to crystallize the
      resulting artificial (betaalpha)(8)-barrel protein HisF-C***C. The analysis of
      its X-ray structure at 2.1 A resolution reveals a striking similarity to wild
      type HisF, helps us to understand its improved stability, and provides further
      insights into the evolution of (betaalpha)(8)-barrel proteins.

PMID- 19166325
TI  - Functional impact of polar and acidic substitutions in the lactose repressor
      hydrophobic monomer.monomer interface with a buried lysine.
AB  - Despite predicted energetic penalties, the charged K84 side chains of tetrameric
      lactose repressor protein (LacI) are found buried within the highly hydrophobic
      monomer.monomer interface that includes side chains of V94 and V96. Once inducer
      binding has occurred, these K84 side chains move to interact with the more
      solvent-exposed side chains of D88 and E100'. Previous studies demonstrated that
      hydrophobic substitutions for K84 increased protein stability and significantly
      impaired the allosteric response. These results indicated that enhanced
      hydrophobic interactions at the monomer.monomer interface remove the energetic
      driving force of the buried charges, decreasing the likelihood of a robust
      conformational change and stabilizing the structure. We hypothesized that
      creating a salt bridge network with the lysine side chains by including nearby
      negatively charged residues might result in a similar outcome. To that end,
      acidic residues, D and E, and their neutral amides, N and Q, were substituted for
      the valines at positions 94 and 96. These variants exhibited one or more of the
      following functional changes: weakened inducer binding, impaired allosteric
      response, and diminished protein stability. For V96D and V96E, ion pair formation
      with K84 appears optimal, and the loss of inducer response exceeds that of the
      hydrophobic K84A and -L variants. However, impacts on functional properties
      indicate that stabilizing the buried positive charge with polar or ion pair
      interactions is not functionally equivalent to structural stabilization via
      hydrophobic enhancement.

PMID- 19166326
TI  - Biosynthesis of undecaprenyl phosphate-galactosamine and undecaprenyl phosphate
      glucose in Francisella novicida.
AB  - Lipid A of Francisella tularensis subsp. novicida contains a galactosamine (GalN)
      residue linked to its 1-phosphate group. As shown in the preceding paper, this
      GalN unit is transferred to lipid A from the precursor undecaprenyl phosphate
      beta-D-GalN. A small portion of the free lipid A of Francisella novicida is
      further modified with a glucose residue at position-6'. We now demonstrate that
      the two F. novicida homologues of Escherichia coli ArnC, designated FlmF1 and
      FlmF2, are essential for lipid A modification with glucose and GalN,
      respectively. Recombinant FlmF1 expressed in E. coli selectively condenses
      undecaprenyl phosphate and UDP-glucose in vitro to form undecaprenyl phosphate
      glucose. Recombinant FlmF2 selectively catalyzes the condensation of undecaprenyl
      phosphate and UDP-N-acetylgalactosamine to generate undecaprenyl phosphate-N
      acetylgalactosamine. On the basis of an analysis of the lipid A composition of
      flmF1 and flmF2 mutants of F. novicida, we conclude that FlmF1 generates the
      donor substrate for the modification of F. novicida free lipid A with glucose,
      whereas FlmF2 generates the immediate precursor of the GalN donor substrate,
      undecaprenyl phosphate-beta-D-GalN. A novel deacetylase, present in membranes of
      F. novicida, removes the acetyl group from undecaprenyl phosphate-N
      acetylgalactosamine to yield undecaprenyl phosphate-beta-D-GalN. This deacetylase
      may have an analogous function to the deformylase that generates undecaprenyl
      phosphate-4-amino-4-deoxy-alpha-l-arabinose from undecaprenyl phosphate-4-deoxy-4
      formylamino-alpha-l-arabinose in polymyxin-resistant strains of E. coli and
      Salmonella typhimurium.

PMID- 19166327
TI  - Identification of undecaprenyl phosphate-beta-D-galactosamine in Francisella
      novicida and its function in lipid A modification.
AB  - Francisella tularensis is a highly infectious pathogen that causes tularemia.
      Francisella lipid A contains an unusual galactosamine (GalN) unit, attached to
      its 1-phosphate moiety. Two genes, flmF2 and flmK, are required for the addition
      of GalN to Francisella lipid A, but the relevant enzymes and the GalN donor
      substrate have not been characterized. We now report the purification and
      identification of a novel minor lipid from Francisella novicida that functions as
      the GalN donor. On the basis of electrospray ionization mass spectrometry
      (ESI/MS) and NMR spectroscopy, we propose that this compound is undecaprenyl
      phosphate-beta-d-GalN. Approximately 0.5 mg of pure lipid was obtained from 10 g
      of F. novicida by chloroform/methanol extraction, followed by DEAE-cellulose
      chromatography, mild alkaline hydrolysis, and thin-layer chromatography. ESI/MS
      in the negative mode revealed a molecular ion [M - H](-) at m/z 1006.699,
      consistent with undecaprenyl phosphate-GalN. (31)P NMR spectroscopy showed a
      single phosphorus atom in the phosphodiester linkage. Selective inverse
      decoupling difference spectroscopy demonstrated that the undecaprenyl phosphate
      group is attached to the anomeric carbon of the sugar. (1)H NMR studies showed
      the presence of a polyisoprene chain and a sugar consistent with a beta-d-GalN
      unit. Heteronuclear multiple-quantum coherence (HMQC) analysis confirmed that
      nitrogen is attached to C-2 of the sugar. Purified undecaprenyl phosphate-beta-d
      GalN supports the in vitro modification of lipid IV(A) by membranes of
      Escherichia coli cells expressing FlmK, an orthologue of E. coli ArnT, the enzyme
      that transfers 4-amino-4-deoxy-l-arabinose to lipid A in polymyxin-resistant
      strains. The discovery of undecaprenyl phosphate-beta-d-GalN suggests Francisella
      modifies lipid A with GalN on the periplasmic surface of the inner membrane.

PMID- 19166328
TI  - Association energetics of cross-reactive and specific antibodies.
AB  - HyHEL-8, HyHEL-10, and HyHEL-26 (HH8, HH10, and HH26, respectively) are murine
      monoclonal IgG(1) antibodies which share over 90% variable-region amino acid
      sequence identity and recognize identical structurally characterized epitopes on
      hen egg white lysozyme (HEL). Previous immunochemical and surface plasmon
      resonance-based studies have shown that these antibodies differ widely in their
      tolerance of mutations in the epitope. While HH8 is the most cross-reactive, HH26
      is rigidified by a more extensive network of intramolecular salt links and is
      highly specific, with both association and dissociation rates strongly affected
      by epitope mutations. HH10 is of intermediate specificity, and epitope mutations
      produce changes primarily in the dissociation rate. Calorimetric characterization
      of the association energetics of these three antibodies with the native antigen
      HEL and with Japanese quail egg white lysozyme (JQL), a naturally occurring avian
      variant, shows that the energetics of interaction correlate with cross-reactivity
      and specificity. These results suggest that the greater cross-reactivity of HH8
      may be mediated by a combination of conformational flexibility and less specific
      intermolecular interactions. Thermodynamic calculations suggest that upon
      association HH8 incurs the largest configurational entropic penalty and also the
      smallest loss of enthalpic driving force with variant antigen. Much smaller
      structural perturbations are expected in the formation of the less flexible HH26
      complex, and the large loss of enthalpic driving force observed with variant
      antigen reflects its specificity. The observed thermodynamic parameters correlate
      well with the observed functional behavior of the antibodies and illustrate
      fundamental differences in thermodynamic characteristics between cross-reactive
      and specific molecular recognition.

PMID- 19166329
TI  - Kinetic evidence for interdomain communication in the allosteric regulation of
      alpha-isopropylmalate synthase from Mycobacterium tuberculosis.
AB  - The enzyme alpha-isopropylmalate synthase from Mycobacterium tuberculosis
      (MtIPMS) has been identified as a possible target for the design of new
      antitubercular therapeutics. Recently, it was shown that MtIPMS is subject to
      slow-onset, feedback inhibition by l-leucine, the first instance of an allosteric
      regulator utilizing this mechanism. Structural studies are inconsistent with
      canonical allosteric mechanisms, including changes to the quaternary structure or
      large, rigid-body conformational changes to the enzyme upon l-leucine binding.
      Thus, the allosteric regulation may result from a discrete inhibitory signal
      transmitted to the active site upon l-leucine binding in the regulatory domain, a
      distance of more than 50 A. To test this mechanism, site-directed mutagenesis was
      employed to construct enzymes with substitutions at phylogenetically conserved
      active site residues near the interface of the catalytic and linker domains. The
      substitutions had wide-ranging effects on the kinetics of l-leucine inhibition,
      with some modest effects on the kinetic parameters of catalysis. The most
      dramatic result was the finding that the Y410F mutant form of MtIPMS is
      insensitive to l-leucine inhibition, suggesting that this residue has completely
      uncoupled the inhibitory signal to the active site. Overall, the data are
      consistent with a mechanism of allosteric regulation described by the interdomain
      communication of the inhibitory signal from the regulatory to catalytic domain
      and implicate the interactions between the linker and catalytic domains as
      critical determinants of inhibitory signal transmission.

PMID- 19166330
TI  - An FTIR investigation of flanking sequence effects on the structure and
      flexibility of DNA binding sites.
AB  - Fourier transform infrared (FTIR) spectroscopy and a library of FTIR marker bands
      have been used to examine the structure and relative flexibilities conferred by
      different flanking sequences on the EcoRI binding site. This approach allowed us
      to examine unique peaks and subtle changes in the spectra of d(AAAGAATTCTTT)(2),
      d(TTCGAATTCGAA)(2), and d(CGCGAATTCGCG)(2) and thereby identify local changes in
      base pairing, base stacking, backbone conformation, glycosidic bond rotation, and
      sugar puckering in the studied sequences. The changes in flanking sequences
      induce differences in the sugar puckers, glycosidic bond rotation, and backbone
      conformations. Varying levels of local flexibility are observed within the
      sequences in agreement with previous biological activity assays. The results also
      provide supporting evidence for the presence of a splay in the G(4)-C(9) base
      pair of the EcoRI binding site and a potential pocket of flexibility at the G(4)
      cleavage site that have been proposed in the literature. In sum, we have
      demonstrated that FTIR is a powerful methodology for studying the effect of
      flanking sequences on DNA structure and flexibility, for it can provide
      information about the local structure of the nucleic acid and the overall
      relative flexibilities conferred by different flanking sequences.

PMID- 19166331
TI  - Grafting of lysozyme and/or poly(ethylene glycol) to prevent biofilm growth on
      stainless steel surfaces.
AB  - In the aim of protecting stainless steel surfaces against protein and/or
      bacterial adhesion, thin films including the glycosidase hen egg white lysozyme
      (HEWL) and/or the synthetic polymer poly(ethylene glycol) (PEG) were covalently
      coated onto flat substrates by wet chemical processes. Chemical grafting of both
      species was carried out by covalent binding to surfaces pretreated by the
      polyamine poly(ethylene imine) (PEI). Surfaces were characterized at each step of
      functionalization by means of reflection-absorption infrared spectroscopy by
      modulation of polarization (PM-RAIRS) and X-ray photoelectron spectroscopy (XPS)
      to determine the atomic and molecular composition of the interfaces,
      respectively. Then, the ability of the so-modified surfaces to prevent protein
      adsorption and bacterial adhesion together with their biocide properties were
      demonstrated by three local tests employing bovine serum albumin (BSA), and the
      bacteria Listeria ivanovii and Micrococcus luteus. A new test was implemented to
      assess the local enzymatic properties of HEWL. Cografting of PEG and HEWL
      resulted in a surface with both antiadhesion and antibacterial properties.

PMID- 19166333
TI  - Metabolites in safety testing (MIST): considerations of mechanisms of toxicity
      with dose, abundance, and duration of treatment.
AB  - In previous papers, we have offered a strategic framework regarding metabolites
      of drugs in humans and the need to assess these in laboratory animal species
      (also termed Metabolites in Safety Testing or MIST; Smith and Obach, Chem. Res.
      Toxicol. (2006) 19, 1570-1579). Three main tenets of this framework were founded
      in (i) comparisons of absolute exposures (as circulating concentrations or total
      body burden), (ii) the nature of the toxicity mechanism (i.e., reversible
      interaction at specific targets versus covalent binding to multiple
      macromolecules), and (iii) the biological matrix in which the metabolite was
      observed (circulatory vs excretory). In the present review, this framework is
      expanded to include a fourth tenet: considerations for the duration of exposure.
      Basic concepts of pharmacology are utilized to rationalize the relationship
      between exposure (to parent drug or metabolite) and various effects ranging from
      desired therapeutic effects through to severe toxicities. Practical
      considerations of human ADME (absorption-distribution-metabolism-excretion) data,
      to determine which metabolites should be further evaluated for safety, are
      discussed. An analysis of recently published human ADME studies shows that the
      number of drug metabolites considered to be important for MIST can be excessively
      high if a simple percentage-of-parent-drug criterion is used without
      consideration of the aforementioned four tenets. Concern over unique human
      metabolites has diminished over the years as experience has shown that
      metabolites of drugs in humans will almost always be observed in laboratory
      animals, although the proportions may vary. Even if a metabolite represents a
      high proportion of the dose in humans and a low proportion in animals, absolute
      abundances in animals frequently exceed that in humans because the doses used in
      animal toxicology studies are much greater than therapeutic doses in humans. The
      review also updates the enzymatic basis for the differences between species and
      how these relate to MIST considerations.

PMID- 19166332
TI  - Mitochondrial DNA adducts in the lung and liver of F344 rats chronically treated
      with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and (S)-4-(methylnitrosamino)
      1-(3-pyridyl)-1-butanol.
AB  - Two recent studies conducted in our laboratory have demonstrated formation and
      accumulation of pyridyloxobutyl (POB) and pyridylhydroxybutyl (PHB) adducts in
      lung and liver total DNA of F344 rats chronically treated with the tobacco
      specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and (R)-
      and (S)-enantiomers of its metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanol (NNAL). In this study, we measured POB and PHB adducts in lung and liver
      mitochondrial DNA (mtDNA), as previous studies suggest a potentially important
      role of mtDNA in carcinogenesis. Rats were sacrificed after 1, 2, 5, 10, 16, and
      20 weeks of treatment with 10 ppm of NNK or (S)-NNAL in drinking water, and mtDNA
      and nuclear DNA (nDNA) adduct levels in the lung and liver were determined by LC
      ESI-MS/MS-SRM. The mean levels of individual POB adducts in mtDNA at all time
      points were slightly higher than those in nDNA for both NNK and (S)-NNAL-treated
      rats in the lung (P < 0.001 for both treatments) but not in the liver (P > 0.05).
      Lung mtDNA of both NNK- and (S)-NNAL-treated rats contained higher concentrations
      of the sum of three POB adducts (P < 0.001 for both treatments) than nDNA, while
      the levels of mtDNA and nDNA total POB adducts in the liver were not
      significantly different in either NNK- or (S)-NNAL-treated rats. Analysis of PHB
      adducts in mtDNA and nDNA produced results similar to those obtained for POB
      adducts. The steady accumulation of the lung and liver mtDNA adducts over the
      course of the study indicates inefficient repair of these adducts in mtDNA. This
      is the first study to examine the formation of NNK- and (S)-NNAL-derived adducts
      in rat mtDNA. The results support the hypothesis that preferential binding of
      tobacco carcinogens to mtDNA of the lung might be functionally important in the
      development of smoking-induced lung cancer.

PMID- 19166334
TI  - Exocyclic DNA adducts as biomarkers of lipid oxidation and predictors of disease.
      Challenges in developing sensitive and specific methods for clinical studies.
AB  - Exocyclic DNA adducts are emerging as potential new tools for the study of
      oxidative stress-related diseases as well as the determination of cancer etiology
      and cancer risk. It is important to determine whether levels of exocyclic DNA
      adducts reflect redox stress in vivo and what role these adducts play in human
      diseases. To answer these important questions, interindividual differences,
      tissue distribution, background levels, and repair have to be assessed. This
      review focuses on recent developments in the use of these adducts as possible
      biomarkers for disease risk related to oxidative stress and on the challenges in
      developing sensitive and specific methods for clinical studies.

PMID- 19166335
TI  - Physicochemical properties of hydrothermally treated hemicellulose from oil palm
      frond.
AB  - Hemicelluloses from oil palm frond (OPF) were extracted using 3 M potassium
      hydroxide (KOH) for 4 h at 40 degrees C with stirring at 400 rpm to obtain
      hemicelluloses A and B. The total yield of the hemicellulose isolated from OPF
      was 33% (dry weight). Both hemicelluloses A and B were then subjected to
      hydrothermal treatment at 121 degrees C and 1.03 x 10(5) Pa for 10, 30, and 50
      min. Physicochemical characterizations of hydrothermally treated hemicelluloses,
      such as Klason lignin content and reducing sugar content, were performed to study
      the effect of autohydrolysis processing on OPF-derived hemicelluloses. It was
      shown that Klason lignin content in hemicellulose A was higher than that in
      hemicellulose B and decreased after hydrothermal treatment. Hydrothermal
      treatment enhanced the solubility of hemicelluloses, which reflects their higher
      reducing sugar content. Monosaccharide analysis using HPLC showed that xylose was
      the predominant monosaccharide for both hemicelluloses A and B.

PMID- 19166336
TI  - Antiatherosclerotic effects of Artemisia princeps Pampanini cv. Sajabal in LDL
      receptor deficient mice.
AB  - Antiatherosclerotic effects of ethanolic extracts of Artemisia princeps Pampanini
      cv. Sajabal (ESJ) were investigated in low-density lipoprotein receptor deficient
      (LDLR(-/-)) mice. The Western diet-induced high levels of total cholesterol and
      triglyceride were similar in the ESJ and control groups. However, circulating
      oxidized LDL was significantly decreased in the ESJ group (p < 0.05). ESJ also
      markedly decreased aortic expression levels of intercellular adhesion molecule-1
      (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-alpha
      (TNF-alpha), and interleukin-1 beta (IL-1 beta), and reduced the aortic lesion
      formation and macrophage accumulation by 36.7% (p < 0.05) and 43% (p < 0.01) in
      the control group, respectively. Additionally, ESJ inhibited atherogenic
      properties with cytokine-induced surface expression of cell adhesion molecules,
      chemokines, and monocyte adhesion to the human umbilical vein endothelial cells
      (HUVECs), and simultaneously suppressed nuclear factor-kappaB (NF-kappaB)
      activation. These results suggest that ethanolic extracts of Artemisia princeps
      Pampanini cv. Sajabal contributes to the antiatherosclerotic and anti
      inflammatory activities in LDLR(-/-) mice.

PMID- 19166337
TI  - Free radical mechanisms for the treatment of methyl tert-butyl ether (MTBE) via
      advanced oxidation/reductive processes in aqueous solutions.

PMID- 19166338
TI  - Induction of macrophage apoptosis by an organochlorine insecticide acetofenate.
AB  - Acetofenate (AF) is a widely used insecticide in China and other regions of
      southeastern Asia. A previous study showed that AF caused adverse developmental
      effects in zebrafish. Macrophages, which play a key role in inflammation, host
      defense, and reactions against a spectrum of autologous and foreign invaders, are
      crucial for innate immunity. However, cytotoxicity and apoptosis of macrophages
      caused by organochlorine pesticides (OCPs) have so far received little attention.
      In this study, we used AF as a model chemical to investigate the cytotoxic
      effects of OCPs on mouse macrophage cell line RAW264.7. Results from cell
      viability and apoptosis assays showed that AF induced apparent apoptosis in RAW
      264.7 cells. Furthermore, AF induced intracellular reactive oxygen species (ROS)
      generation and DNA damage and resulted in the alteration of a series of signaling
      molecules including up-regulation of p53 and cytochrome c protein levels, decline
      of the Bcl-2/Bax protein ratio, and activation of the caspases cascade through
      caspase-9 and caspase-3. These results, for the first time, revealed that the
      increase of endogenous ROS and DNA damage comediating OCP-induced apoptosis in
      macrophages may be by the mitochondria and p53 signal pathway. Our results
      suggested that macrophages are involved in AF-induced adverse immune effects.
      Considering the ubiquitous environmental presence of OCPs, this study provided
      new information on the potential long-term physiological and immunological
      effects due to chronic exposures to OCPs.

PMID- 19166340
TI  - Evidence of natural isotopic distribution from single-molecule SERS.
AB  - We report on the observation of the natural isotopic spread of carbon from single
      molecule surface-enhanced Raman spectroscopy (SM-SERS). By choosing a dye
      molecule with a very localized Raman-active vibration in a cyano bond (C[triple
      bond]N triple bond), we observe (in a SERS colloidal liquid) a small fraction of
      SM-SERS events where the frequency of the cyano mode is softened and in agreement
      with the effect of substituting (12)C by the next most abundant isotope, (13)C.
      This example adds another demonstration of single-molecule sensitivity in SERS
      through isotopic editing, which in this case is done not by artificial isotopic
      editing but rather by nature itself. It also highlights SERS as a unique
      spectroscopic tool that is capable of detecting an isotopic change in one atom of
      a single molecule.

PMID- 19166339
TI  - Differences in metabolite-mediated toxicity of tamoxifen in rodents versus humans
      elucidated with DNA/microsome electro-optical arrays and nanoreactors.
AB  - Tamoxifen, a therapeutic and chemopreventive breast cancer drug, was chosen as a
      model compound because of acknowledged species specific toxicity differences.
      Emerging approaches utilizing electro-optical arrays and nanoreactors based on
      DNA/microsome films were used to compare metabolite-mediated toxicity differences
      of tamoxifen in rodents versus humans. Hits triggered by liver enzyme metabolism
      were first provided by arrays utilizing a DNA damage end point. The arrays
      feature thin-film spots containing an electrochemiluminescent (ECL) ruthenium
      polymer ([Ru(bpy)(2)PVP(10)](2+); PVP, polyvinylpyridine), DNA, and liver
      microsomes. When DNA damage resulted from reactions with tamoxifen metabolites,
      it was detected by an increase in light from the oxidation of the damaged DNA by
      the ECL metallopolymer. The slope of ECL generation versus enzyme reaction time
      correlated with the rate of DNA damage. An approximate 2-fold greater ECL
      turnover rate was observed for spots with rat liver microsomes compared to that
      with human liver microsomes. These results were supported by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) analysis of reaction products
      using nanoreactors featuring analogous films on silica nanoparticles, allowing
      the direct measurement of the relative formation rate for alpha-(N(2)
      deoxyguanosinyl)tamoxifen. We observed 2-5-fold more rapid formation rates for
      three major metabolites, i.e., alpha-hydroxytamoxifen, 4-hydroxytamoxifen, and
      tamoxifen N-oxide, catalyzed by rat liver microsomes compared to human liver
      microsomes. Comparable formation rates were observed for N-desmethyl tamoxifen
      with rat and human liver microsomes. A better detoxifying capacity for human
      liver microsomes than rat liver microsomes was confirmed utilizing
      glucuronyltransferase in microsomes together with UDP-glucuronic acid. Taken
      together, lower genotoxicity and higher detoxication rates presented by human
      liver microsomes correlate with the lower risk of tamoxifen in causing liver
      carcinoma in humans, provided the glucuronidation pathway is active.

PMID- 19166343
TI  - Cell cycle-dependent phosphorylation of MAN1.
AB  - The LEM (LAP2beta, Emerin, and MAN1) proteins are essential for nuclear membrane
      targeting to chromatin via an association with barrier-to-autointegration factor
      (BAF). Herein, we focused on the mitotic phosphorylation of MAN1 and its
      biological role. MAN1 was phosphorylated in a cell cycle-dependent manner in the
      Xenopus egg cell-free system, and the mitotic phosphorylation at the N-terminal
      region of MAN1 suppressed the binding of MAN1 to BAF. Titansphere column
      chromatography followed by MS/MS sequencing identified at least three M-phase
      specific phosphorylation sites, Thr-209, Ser-351, and Ser-402, and one cell cycle
      independent phosphorylation site, Ser-463. An in vitro BAF binding assay
      involving mutants S402A and S402E suggested that the phosphorylation of Ser-402
      was important for regulation of the binding of MAN1 to BAF.

PMID- 19166341
TI  - Nanoparticles of adaptive supramolecular networks self-assembled from nucleotides
      and lanthanide ions.
AB  - Amorphous nanoparticles of supramolecular coordination polymer networks are
      spontaneously self-assembled from nucleotides and lanthanide ions in water. They
      show intrinsic functions such as energy transfer from nucleobase to lanthanide
      ions and excellent performance as contrast enhancing agents for magnetic
      resonance imaging (MRI). Furthermore, adaptive inclusion properties are observed
      in the self-assembly process: functional materials such as fluorescent dyes,
      metal nanoparticles, and proteins are facilely encapsulated. Dyes in these
      nanoparticles fluoresce in high quantum yields with a single exponential decay,
      indicating that guest molecules are monomerically wrapped in the network. Gold
      nanoparticles and ferritin were also wrapped by the supramolecular shells. In
      addition, these nucleotide/lanthanide nanoparticles also serve as scaffolds for
      immobilizing enzymes. The adaptive nature of present supramolecular nanoparticles
      provides a versatile platform that can be utilized in a variety of applications
      ranging from material to biomedical sciences. As examples, biocompatibility and
      liver-directing characteristics in in vivo tissue localization experiments are
      demonstrated.

PMID- 19166344
TI  - Intensely luminescent alkynyl-phosphine gold(I)-copper(I) complexes: synthesis,
      characterization, photophysical, and computational studies.
AB  - The reactions between the diphosphino-alkynyl gold complexes (XC6H4C2Au)PR2-C6H4
      PR2(AuC2C6H4X) with Cu+ lead to the formation of a family of heterometallic
      clusters of the general formula [{Au3Cu2(C2C6H4X)6}Au3(PR2C6H4PR2)3][PF6]2 (X =
      NO2, H, OMe, NMe2; R = C6H5, NC4H4). These complexes adopt the same structural
      pattern and consist of a heterometallic alkynyl cluster [Au3Cu2(C2C6H4X)6]-
      "wrapped" by the cationic [Au3(PR2C6H4PR2)3]3+ "belt". The novel compounds were
      characterized by NMR spectroscopy and ESI-MS measurements. A systematic study of
      their luminescence properties revealed efficient room-temperature phosphorescence
      in solution with remarkably weak quenching by molecular oxygen. The photophysical
      experiments demonstrate that the increase in the electron donor ability of the
      alkynyl ligands and the electron-withdrawing character of the diphosphines
      results in the bathochromic shift of emission maxima (in the 576-686 nm range)
      and a decrease in the luminescence quantum yield. The electronic structure
      calculations showed that variations of X or R substituents have very little
      effect on the structural parameters but display a significant influence on the
      electronic properties of the clusters and characteristics of luminescence. The
      metal-centered triplet emission within the heterometallic alkynyl cluster is
      suggested to play a key role in the observed phosphorescence.

PMID- 19166345
TI  - High constitutive activity and a G-protein-independent high-affinity state of the
      human histamine H(4)-receptor.
AB  - The human histamine H(4)-receptor (hH(4)R) is expressed in mast cells and
      eosinophils and mediates histamine (HA)-induced chemotaxis via G(i)-proteins. For
      a detailed investigation of hH(4)R/G(i)-protein interaction, we coexpressed the
      hH(4)R with Galpha(i2) and Gbeta(1)gamma(2) as well as an hH(4)R-Galpha(i2)
      fusion protein with Gbeta(1)gamma(2) in Sf9 insect cells. The agonist radioligand
      [(3)H]HA showed a K(D) value of approximately 10 nM at hH(4)R and hH(4)R
      Galpha(i2). The high-affinity states of hH(4)R and hH(4)R-Galpha(i2) were
      insensitive to guanosine 5'-[gamma-thio]triphosphate (GTPgammaS). The affinity of
      [(3)H]HA for hH(4)R was retained in the absence of mammalian G(i)-proteins. In
      steady-state GTPase- and [(35)S]GTPgammaS-binding assays, hH(4)R exhibited high
      constitutive activity and uncommon insensitivity to Na(+). Thioperamide (THIO)
      was only a partial inverse agonist. Addition of HA or THIO to baculovirus
      infected (hH(4)R + Galpha(i2) + Gbeta(1)gamma(2)) Sf9 cells increased the B(max)
      in [(3)H]HA binding, but not in immunoblots, suggesting conformational
      instability and ligand-induced stabilization of membrane-integrated hH(4)R. No
      effect was observed on hH(4)R-Galpha(i2) expression, neither in [(3)H]HA binding
      nor in immunoblot. However, the expression level of hH(4)R-Galpha(i2) was
      consistently higher compared to hH(4)R, suggesting chaperone-like or stabilizing
      effects of Galpha(i2) on hH(4)R. In 37 degrees C stability assays, HA stabilized
      hH(4)R, and THIO even restored misfolded [(3)H]HA binding sites. Inhibition of
      hH(4)R glycosylation by tunicamycin reduced the [(3)H]HA binding B(max) value. In
      conclusion, (i) hH(4)R shows high constitutive activity and structural
      instability; (ii) hH(4)R shows a G-protein-independent high-affinity state; (iii)
      hH(4)R conformation is stabilized by agonists, inverse agonists and G-proteins;
      (iv) hH(4)R glycosylation is essential for cell-surface expression of intact
      hH(4)R.

PMID- 19166346
TI  - Synthesis of (+)- and (-)-monanchorin.
AB  - The optically pure epoxy acetal was converted to the protected guanidino alcohol
      by reaction with NaN(3) in DMF, hydrogenation of the azide, and reaction of the
      amine with MeSC(NBoc)NHBoc, AgNO(3), and Et(3)N. Treatment of the protected
      guanidino alcohol with 9:1 CDCl(3)/TFA afforded monanchorin, whose absolute
      stereochemistry was assigned as shown.

PMID- 19166347
TI  - Ran GTPase regulates hemocytic phagocytosis of shrimp by interaction with myosin.
AB  - Ran GTPases, one family of small G protein superfamily, have been widely
      demonstrated to be involved in the transport system between cytoplasm and the
      nucleus. However, the function of Ran GTPase in immunity remains unclear. In our
      study, it was found that the Ran GTPase (designated as PjRan) was up-regulated in
      virus-resistant shrimp, indicating that the PjRan might be implicated in the
      innate immune system against virus infection. On the basis of protein
      interactions, it was found that the PjRan interacted with myosin, a crucial
      protein in the process of phagocytosis to form a protein complex. The RNAi and
      mRNA assays showed that the PjRan could regulate shrimp hemocytic phagocytosis.
      Further data evidenced that the depletion of PjRan by RNAi caused a significant
      increase of virus copies, and the overexpression of PjRan resulted in a
      significant decrease of virus copies, suggesting that the PjRan participated in
      the antiviral immunity by regulating phagocytosis. Therefore, our study revealed
      a completely novel aspect of Ran GTPase in phagocytosis by the direct interaction
      with the cytoskeleton protein and presented a novel pathway concerning to
      antiviral immunity, which will help to better understand the molecular events in
      immune response against virus infection in invertebrates.

PMID- 19166348
TI  - Shrimp study exposes mechanisms of innate immunity.

PMID- 19166349
TI  - Solution structure and dynamics of the small GTPase RalB in its active
      conformation: significance for effector protein binding.
AB  - The small G proteins RalA/B have a crucial function in the regulatory network
      that couples extracellular signals with appropriate cellular responses. RalA/B
      are an important component of the Ras signaling pathway and, in addition to their
      role in membrane trafficking, are implicated in the initiation and maintenance of
      tumorigenic transformation of human cells. RalA and RalB share 85% sequence
      identity and collaborate in supporting cancer cell proliferation but have
      markedly different effects. RalA is important in mediating proliferation, while
      depletion of RalB results in transformed cells undergoing apoptosis. Crystal
      structures of RalA in the free form and in complex with its effectors, Sec5 and
      Exo84, have been solved. Here we have determined the solution structure of free
      RalB bound to the GTP analogue GMPPNP to an RMSD of 0.6 A. We show that, while
      the overall architecture of RalB is very similar to the crystal structure of
      RalA, differences exist in the switch regions, which are sensitive to the bound
      nucleotide. Backbone 15N dynamics suggest that there are four regions of disorder
      in RalB: the P-loop, switch I, switch II, and the loop comprising residues 116
      121, which has a single residue insertion compared to RalA. 31P NMR data and the
      structure of RalB.GMPPNP show that the switch regions predominantly adopt state 1
      (Ras nomenclature) in the unbound form, which in Ras is not competent to bind
      effectors. In contrast, 31P NMR analysis of RalB.GTP reveals that conformations
      corresponding to states 1 and 2 are both sampled in solution and that addition of
      an effector protein only partially stabilizes state 2.

PMID- 19166350
TI  - N2'-->p3' phosphoramidate glycerol nucleic acid as a potential alternative
      genetic system.
AB  - Glycerol nucleic acid (GNA) is an interesting base-pairing system with an
      acyclic, three-carbon backbone. In the present study, GNA analogues with N2'-
      >P3' phosphoramidate linkages (npGNA) have been synthesized and their base
      pairing properties examined. Thermal denaturation and circular dichroism studies
      show that npGNA can form stable duplexes with itself and with GNA. Furthermore,
      we show that npGNA can be assembled by template-directed ligation of 3'-imidazole
      activated-2'-amino GNA dinucleotides. These results suggest that npGNA is a
      potential candidate for a self-replicating system based upon phosphoramidate
      linkages.

PMID- 19166351
TI  - A tandem approach to photoactivated olefin metathesis: combining a photoacid
      generator with an acid activated catalyst.
AB  - Combining an acid activated precatalyst with a photoacid generator (PAG) in the
      presence of ultraviolet light resulted in a highly efficient catalyst for olefin
      metathesis. The tandem system of precatalyst and PAG was capable of both ring
      closing metathesis (RCM) and ring opening metathesis polymerization (ROMP) in
      good to excellent conversion. Mechanistic investigations revealed that the
      catalytically active species is very similar to that of other well-known Ru-based
      catalysts.

PMID- 19166352
TI  - Eugenia jambolana Lam. berry extract inhibits growth and induces apoptosis of
      human breast cancer but not non-tumorigenic breast cells.
AB  - The ripe purple berries of the native Indian plant Eugenia jambolana Lam., known
      as Jamun, are popularly consumed and available in the United States in Florida
      and Hawaii. Despite the growing body of data on the chemopreventive potential of
      edible berry extracts, there is paucity of such data for Jamun fruit. Therefore
      our laboratory initiated the current study with the following objectives: (1) to
      prepare a standardized Jamun fruit extract (JFE) for biological studies and (2)
      to investigate the antiproliferative and pro-apoptotic effects of JFE in estrogen
      dependent/aromatase positive (MCF-7aro), and estrogen independent (MDA-MB-231)
      breast cancer cells, and in a normal/nontumorigenic (MCF-10A) breast cell line.
      JFE was standardized to anthocyanin content using the pH differential method, and
      individual anthocyanins were identified by high performance liquid chromatography
      with ultraviolet (HPLC-UV) and tandem mass spectrometry (LC-MS/MS) methods. JFE
      contained 3.5% anthocyanins (as cyanidin-3-glucoside equivalents) which occur as
      diglucosides of five anthocyanidins/aglycons: delphinidin, cyanidin, petunidin,
      peonidin and malvidin. In the proliferation assay, JFE was most effective against
      MCF-7aro (IC(50) = 27 microg/mL), followed by MDA-MB-231 (IC(50) = 40 microg/mL)
      breast cancer cells. Importantly, JFE exhibited only mild antiproliferative
      effects against the normal MCF-10A (IC(50) > 100 microg/mL) breast cells.
      Similarly, JFE (at 200 microg/mL) exhibited pro-apoptotic effects against the MCF
      7aro (p <or= 0.05) and the MDA-MB-231 (p <or= 0.01) breast cancer cells, but not
      toward the normal MCF-10A breast cells. These studies suggest that JFE may have
      potential beneficial effects against breast cancer.

PMID- 19166353
TI  - Reactivity of (C5Me5)3LaL(x) complexes: synthesis of a
      tris(pentamethylcyclopentadienyl) complex with two additional ligands,
      (C5Me5)3La(NCCMe3)2.
AB  - The limits of steric crowding in tris(pentamethylcyclopentadienyl) complexes have
      been expanded by isolation of the first compound with this ligand set and two
      additional ligands, (C(5)Me(5))(3)ML(2). This result was obtained in a study of
      the effect of added ligands on the reactivity of sterically crowded
      (C(5)Me(5))(3)La, 1. Although neither THF nor Ph(3)PO formed crystallographically
      characterizable (C(5)Me(5))(3)LaL(x) complexes with 1, these
      (C(5)Me(5))(3)La/L(x) mixtures displayed enhanced reactivity compared to 1 with
      substrates such as C(8)H(8) and CO(2). Attempts to use adamantyl azide, AdN(3),
      to make (C(5)Me(5))(3)LaL(x) complexes led to the first example of azide
      insertion into a metal cyclopentadienyl linkage to generate
      (C(5)Me(5))(2)La[eta(2)-(N,N')-(C(5)Me(5))NN'N''Ad](N(3)Ad). Addition of Me(3)CCN
      to 1 produced the first crystallographically characterized (C(5)Me(5))(3)ML(2)
      complex, (C(5)Me(5))(3)La(NCCMe(3))(2).

PMID- 19166354
TI  - Identifying the features of purine dNTPs that allow accurate and efficient DNA
      replication by herpes simplex virus I DNA polymerase.
AB  - To accurately replicate its viral genome, the Herpes Simplex Virus 1 (HSV-1) DNA
      polymerase usually polymerizes the correct natural 2'-deoxy-5'-triphosphate
      (dNTP) opposite the template base being replicated. We employed a series of
      purine-dNTP analogues to determine the chemical features of the base necessary
      for the herpes polymerase to avoid polymerizing incorrect dNTPs. The enzyme uses
      N-3 to prevent misincorporation of purine dNTPs but does not require N-3 for
      correct polymerization. A free pair of electrons on N-1 also helps prevent
      misincorporation opposite A, C, and G and strongly drives polymerization opposite
      T. N6 contributes a small amount both for preventing misincorporation and for
      correct polymerization. Within the context of guanine in either the incoming dNTP
      or the template base being replicated, N2 prevents misincorporation opposite
      adenine but plays at most a minor role for incorporation opposite C. In contrast,
      adding N2 to the dNTPs of either adenine, purine, 6-chloropurine, or 1
      deazapurine greatly enhances incorporation opposite C, likely via the formation
      of a hydrogen bond between N2 of the purine and O2 of the pyrimidine. Herpes
      polymerase is very sensitive to the structure of the base pair at the primer 3'
      terminus since eliminating N-1, N-3, or N6 from a purine nucleotide at the primer
      3'-terminus interfered with polymerization of the next two dNTPs. The biological
      and evolutionary implications of these data are discussed.

PMID- 19166355
TI  - Coordinating the two protomer active sites of human topoisomerase IIalpha: nicks
      as topoisomerase II poisons.
AB  - Topoisomerase II modulates DNA topology by generating double-stranded breaks in
      DNA. Results of the current study indicate that the presence of a nick at one
      scissile bond dramatically increases the rate of cleavage by human topoisomerase
      IIalpha at the scissile bond on the opposite strand. We propose that this
      enhanced activity at the second strand coordinates the two protomer subunits of
      topoisomerase II and allows the enzyme to create double-stranded breaks. Finally,
      the presence of a nick on one strand induces cleavage on the opposite strand.
      Thus, nicks are topoisomerase II poisons that generate novel sites of DNA
      cleavage.

PMID- 19166356
TI  - Characterization of the ligand and DNA binding properties of a putative archaeal
      regulator ST1710.
AB  - While a rich collection of bacterium-like regulating proteins has been identified
      in the archaeal genome, few of them have been studied at the molecular level. In
      this study, we characterized the ligand and DNA binding properties of a putative
      regulator ST1710 from the archaeon Sulfolobus tokodaii. ST1710 is homologous to
      the multiple-antibiotic resistance repressor (MarR) family bacterial regulators.
      The protein consists of a ligand binding site, partially overlapping with a
      winged helix-turn-helix DNA binding site. We characterized the interactions
      between ST1710 and three ligands, salicylate, carbonyl cyanide m
      chlorophenylhydrazone (CCCP), and ethidium, which bind to bacterial MarRs. The
      binding affinities of the ligands for ST1710 were comparable to their affinities
      for the bacterial MarRs. The ligand binding was temperature sensitive and caused
      conformational changes in ST1710. To investigate the effect of ligand binding on
      the interaction between ST1710 and DNA, we fluorescently labeled a 47mer dsDNA
      (ST1) containing a putative ST1710 recognition site and determined the
      dissociation constant between ST1 and ST1710 using the fluorescence polarization
      method. The binding affinity almost doubled from 10 degrees C (Kd = 618 +/- 34
      nM) to 30 degreesC (Kd = 334 +/- 15 nM), and again from 30 to 50 degrees C (Kd =
      189 +/- 9 nM). This result suggests that under the natural living condition (80
      degrees C) of S. tokodaii, the binding affinity might increase even further. The
      presence of CCCP and salicylate suppressed ST1710-ST1 interaction, indicating
      that ST1710 functioned as a repressor.

PMID- 19166362
TI  - {Mn6}n single-chain magnet bearing azides and di-2-pyridylketone-derived ligands.
AB  - The synthesis, structure, and magnetochemical characterization of a new manganese
      single-chain magnet are reported. The compound is a chain of repeating Mn(6)
      units bridged by end-on azide groups and exhibits magnetization hysteresis loops.

PMID- 19166363
TI  - A nontwisted, ferromagnetically coupled Mn(III)3O triangular complex from the use
      of 2,6-bis(hydroxymethyl)-p-cresol.
AB  - The reaction between Mn(O(2)CMe)(2) x 4 H(2)O and hmcH(3) [hmcH(3) = 2,6
      bis(hydroxymethyl)-p-cresol] in CH(2)Cl(2) in the presence of NEt(3) affords the
      Mn(III)(3) complex [NEt(3)(CH(2)Cl)](2)[Mn(3)O(hmcH)(3)(hmcH(2))(3)] (1). The
      anion of 1 contains a [Mn(III)(3)(mu(3)-O)](7+) triangular core, with the central
      O(2-) ion lying above the Mn(3) plane. The complex is ferromagnetically coupled
      with a resulting S = 6 ground state.

PMID- 19166364
TI  - Theoretical studies of N2 reduction to ammonia in Fe(dmpe)2N2.
AB  - Electronic structure calculations using density functional theory were performed
      on potential intermediates in the reaction of Fe(dmpe)(2)N(2) (dmpe = 1,2
      bis(dimethylphosphino)ethane) with protons. Three mechanisms were investigated
      and compared, and the possibility of a two-electron reduction by a sacrificial
      Fe(dmpe)(2)N(2) complex was considered in each mechanism. A Chatt-like mechanism,
      involving the stepwise addition of protons to the terminal nitrogen, was found to
      be the least favorable. A second pathway involving dimerization of the
      Fe(dmpe)(2)N(2) complex, followed by the stepwise addition of protons leading to
      hydrazine, was found to be energetically favorable; however many of the dimeric
      intermediates prefer to dissociate into monomers. A third mechanism proceeding
      through diazene and hydrazine intermediates, formed by alternating protonation of
      each nitrogen atom, was found to be the most energetically favorable.

PMID- 19166361
TI  - Comparative docking study of anibamine as the first natural product CCR5
      antagonist in CCR5 homology models.
AB  - Anibamine, a novel pyridine quaternary alkaloid recently isolated from Aniba sp.,
      has been found to effectively bind to the chemokine receptor CCR5 with an IC(50)
      at 1 microM in competition with (125)I-gp120, an HIV viral envelope protein
      binding to CCR5 with high affinity. Since CCR5, a G-protein-coupled receptor, is
      an essential coreceptor for the human immunodeficiency virus type I (HIV-1) entry
      to host cells, a CCR5 antagonist that inhibits the cellular entry of HIV-1
      provides a new therapy choice for the treatment of HIV. Anibamine provides a
      novel structural skeleton that is remarkably different from all lead compounds
      previously identified as CCR5 antagonists. Here, we report comparative docking
      studies of anibamine with several other known CCR5 antagonists in two CCR5
      homology models built based on the crystal structures of bovine rhodopsin and
      human beta(2)-adrenergic receptor. The binding pocket of anibamine has some
      common features shared with other high affinity CCR5 antagonists, suggesting that
      they may bind in similar binding sites and/or modes. At the same time, several
      unique binding features of anibamine were identified, and it will likely prove
      beneficial in future molecular design of novel CCR5 antagonists based on the
      anibamine scaffold.

PMID- 19166365
TI  - Geometric isomerism in pentacoordinate Cu2+ complexes: equilibrium, kinetic, and
      density functional theory studies reveal the existence of equilibrium between
      square pyramidal and trigonal bipyramidal forms for a tren-derived ligand.
AB  - A ligand (L1) (bis(aminoethyl)[2-(4-quinolylmethyl)aminoethyl]amine) containing a
      4-quinolylmethyl group attached to one of the terminal amino groups of tris(2
      aminoethyl)amine (tren) has been prepared, and its protonation constants and
      stability constants for the formation of Cu(2+) complexes have been determined.
      Kinetic studies on the formation of Cu(2+) complexes in slightly acidic solutions
      and on the acid-promoted complex decomposition strongly suggest that the Cu(2+)
      L1 complex exists in solution as a mixture of two species, one of them showing a
      trigonal bipyramidal (tbp) coordination environment with an absorption maximum at
      890 nm in the electronic spectrum, and the other one being square pyramidal (sp)
      with a maximum at 660 nm. In acidic solution only a species with tbp geometry is
      formed, whereas in neutral and basic solutions a mixture of species with tbp and
      sp geometries is formed. The results of density functional theory (DFT)
      calculations indicate that these results can be rationalized by invoking the
      existence of an equilibrium of hydrolysis of the Cu-N bond with the amino group
      supporting the quinoline ring so that CuL1(2+) would be actually a mixture of tbp
      [CuL1(H(2)O)](2+) and sp [CuL1(H(2)O)(2)](2+). As there are many Cu(2+)-polyamine
      complexes with electronic spectra that show two overlapping bands at wavelengths
      close to those observed for the Cu(2+)-L1 complex, the existence of this kind of
      equilibrium between species with two different geometries can be quite common in
      the chemistry of these compounds. A correlation found between the position of the
      absorption maximum and the tau parameter measuring the distortion from the
      idealized tbp and sp geometries can be used to estimate the actual geometry in
      solution of this kind of complex.

PMID- 19166366
TI  - From simple diols to carbohydrate derivatives of phenylarsonic acid.
AB  - A series of spiro-arsoranes bearing a phenyl moiety as the fifth substituent were
      synthesized applying open-chain, as well as cyclic vicinal diols, as chelating
      molecules by condensation reactions in aprotic solvents. The products synthesized
      are the spiro compounds of the general formula PhAs(DiolH(-2))(2) derived from
      the vicinal diols meso-2,3-butanediol, PhAs(meso-2,3-ButdH(-2))(2) (1), exo-cis
      2,3-norbornanediol, PhAs{exo-cis-NobdH(-2)}(2) (2), cis-1,2-cyclopentanediol,
      PhAs(cis-1,2-CptdH(-2))(2) (3), anhydroerythritol, PhAs(AnErytH(-2))(2) (4), cis
      1,2-cyclohexanediol, PhAs(cis-1,2-ChxdH(-2))(2) (5), and rac-trans-1,2
      cyclohexanediol, rac-{PhAs(trans-1,2-ChxdH(-2))(2)} (6) which were identified as
      mononuclear compounds. A novel dimeric double-spiro environment for oxyarsoranes
      was found in the reaction products derived from the sterically demanding diols
      1,1'-bicyclohexyl-1,1'-diol {PhAs(BhxdH(-2))O}(2) (7) and perfluorpinacol,
      {PhAs(FpinH(-2))O}(2) (8). The stability of the compounds in acidic and neutral
      aqueous media in the presence of organic co-solvents was investigated. A
      convenient synthetic procedure for spiro-oxyarsoranes, applying water as the
      solvent, was developed and proven to be advantageous. All of the compounds
      synthesized in this study were characterized by means of melting-point
      measurement, single-crystal X-ray analysis, NMR, IR, Raman, UV/vis, and mass
      spectrometry. The principles found for these reactions were valid for the methyl
      glycosides of beta-D-ribofuranose and alpha-D-mannopyranose. The spiro-arsorane
      derived from methyl alpha-D-mannopyranoside, PhAs(Me-alpha-D-Manp2,3H(-2))(2)
      (9), is the first example of a structurally characterized carbohydrate-arsenic(V)
      compound.

PMID- 19166367
TI  - Dithienylcyclopentenes-containing transition metal bisterpyridine complexes
      directed toward molecular electronic applications.
AB  - There is continuing interest in the design and synthesis of functional materials
      for applications in molecular electronics and information storage. Of particular
      interest are systems that can provide multiple means for controlling transport
      through well-defined and stable electronic and/or redox states. We report herein
      the synthesis and characterization of a system containing transition-metal
      complexes along with dithienylethene (DTE) units so as to achieve photo and redox
      control of transport. A facile synthetic methodology was developed to assemble
      and couple metal terpyridine (M-tpy) complexes with the photochromic DTE unit in
      a linear structure with M-DTE-M or DTE-M-DTE arrangements, with emphasis on the
      latter series. The photochromic properties of these assemblies were examined by
      monitoring the changes in their UV/vis spectra upon irradiation at specific
      wavelengths capable of triggering the open/closed isomerization in the DTE units.
      Their electrochromic properties were studied via cyclic voltammetry and
      controlled potential electrolysis experiments. Complexes 10 (PhDTE-Fe-DTEPh) and
      11 (PhDTE-Co-DTEPh) with phenyl-ending groups were found to be both photochromic
      and electrochromic, so they represent excellent candidates for further
      elaborations. The Fe(II)-containing complex 8 (ClDTE-Fe-DTECl) with chloride
      ending groups was photochromically inactive but could undergo the
      electrochemically induced open-to-closed isomerization. On the contrary, the
      electrochromically inactive complex 9 (ClDTE-Co-DTECl) underwent cyclization
      under ultraviolet irradiation.

PMID- 19166368
TI  - Blue phosphorescent Ir(III) complex with high color purity: fac-tris(2',6'
      difluoro-2,3'-bipyridinato-N,C(4'))iridium(III).
AB  - A blue phosphorescent iridium(III) complex (1) bearing fluorine-substituted
      bipyridine (dfpypy) has been synthesized and characterized to investigate the
      effect of the substitution and replacement of the phenyl ring in ppy
      (phenylpyridine) with pyridine on the solid state structure and its
      photoluminescence. The optical properties and electrochemical behaviors of 1 have
      also been systematically evaluated. The structure of 1 has also been determined
      by a single-crystal X-ray diffraction analysis. There are varied intermolecular
      interactions caused by the pyridine and fluorine substituents, such as C-H...N, C
      H...F, and pi...pi interactions of either face-to-face type or edge-to-face C
      H...pi and halogen...pi in crystal packing. In electrochemistry, the remarkably
      higher oxidation potential than that of FIrpic was observed. The emission
      lambda(max) of 1 at room temperature is at 438 nm with a higher PL quantum
      efficiency. Complex 1 exhibits intense blue emission with high color purity (CIE
      x = 0.14, y = 0.12), which has been attributed to metal-to-ligand charge-transfer
      triplet emission based on DFT calculations.

PMID- 19166369
TI  - Getting a clue to the hydrolytic activation of white phosphorus: the generation
      and stabilization of P(OH)2PHPHPH(OH) at ruthenium centers.
AB  - The bimetallic compound [{CpRu(PPh(3))(2)}(2)(mu,eta(1:1)-P(4))][CF(3)SO(3)](2),
      in which the tetrahedral P(4) is bound to two CpRu(PPh(3))(2) fragments, slowly
      reacts under mild conditions with a moderate excess of water (1:20) to yield a
      mixture of compounds. Among the hydrolysis products, the new, remarkably stable
      complexes [{CpRu(PPh(3))}{CpRu(PPh(3))(2)}{mu(1,4:3),eta(2:1)
      P(OH)(2)PHPHPH(OH)}](CF(3)SO(3))(2) (2) and
      [{CpRu(PPh(3))(2)}{CpRu(PPh(3)){P(OH)(3))}(mu,eta(1:1)-P(2)H(4))](CF(3)SO(3))(2)
      (3) have been isolated. In the former, the previously unknown 1,1,4
      tris(hydroxy)tetraphosphane molecule, P(OH)(2)PHPHPH(OH), is 1,4- and,
      respectively, 3-coordinated to the CpRu(PPh(3)) and the CpRu(PPh(3))(2) moieties;
      in the latter, the diphosphane P(2)H(4) is stabilized through coordination to two
      different metal fragments. All of the compounds were characterized by elemental
      analyses and IR and NMR spectroscopy. The crystal structure of 2 was determined
      by X-ray analysis. The formation of the hydroxytetraphosphane, containing the
      tetraphosphorus entity, provides a clue to the hydrolytic activation of the P(4)
      molecule.

PMID- 19166370
TI  - One-dimensional Co(II) and Cu(II) coordination polymers and a discrete Cu(II)4
      complex of carboxylate-appended (2-pyridyl)alkylamine ligands: spin-canting and
      anti-/ferromagnetic coupling.
AB  - Structural characterization of the newly synthesized complexes
      [M(I)I(L(1)OO)(xH2O)][ClO4] x 2 H2O [M = Co, x = 1 (1); M = Cu, x = 0 (2); L(1)OO
      = 3-[(2-(pyridin-2-yl)ethyl){2-(pyridin-2-yl)methyl}amino]propionate] reveals
      that 1 and 2 are 1D chainlike coordination polymers. A tridentate variety of this
      ligand afforded a discrete tetranuclear complex {[Cu(I)I(L(2)OO)(OClO3)]}4 x MeCN
      (3) [L(2)OO- = 3-[N-methyl-{2-(pyridine-2-yl)ethyl}amino]propionate]. Analysis of
      the crystal packing diagrams reveals extensive pi-pi stacking in 1 and C-H...O
      hydrogen bonding interactions in 3, leading to the formation of network
      structures. For these complexes, absorption spectral properties have been
      investigated. All three complexes exhibit exchange interaction between the M(II)
      ions through a syn-anti bridging carboxylate pathway. Magnetic studies on 1 show
      spontaneous magnetization below 5 K, which corresponds to the presence of spin
      canted antiferromagnetism. At T = 2 K, the values of coercive field (H(c)) and
      remnant magnetization (M(r)) are 200 G and 0.019 muB, respectively. Analysis of
      the magnetic data through spin Hamiltonians in the form HH = sigma(i<j)(n) 
      J(ij)S(i)S(j) (J is positive for a ferromagnetic interaction and negative for an
      antiferromagnetic interaction) leads to the following set of best-fit parameters:
      J = -2.65(2), -0.66(1), and +12.2(2) cm(-1) for 1, 2, and 3, respectively. An
      attempt has been made to rationalize the observed magnetic behavior.

PMID- 19166371
TI  - Interaction of transuranium elements with biologically important molecules:
      structural and spectroscopic study of NP(V) complexes with imidazole.
AB  - New Np(V) complexes with imidazole, [NpO(2)(CH(3)COO)(Im)(2)(H(2)O)],
      [(NpO(2))(2)(C(2)O(4))(Im)(6)] x 5 Im x H(2)O, and [NpO(2)(NO(2))(Im)(4)], were
      synthesized. Their crystal structures were determined using X-ray single-crystal
      diffractometry. The crystal structures are confirmed by IR and UV-vis
      spectroscopic data. In all three complexes, neptunium coordinates the imidazole
      molecule through the nitrogen atom. These complexes are the first example of
      direct bonding of the imidazole molecule to the actinide atom. These results
      suggest that coordination of histidine residue in proteins or other imidazole
      containing biologically important molecules could occur under usual biological
      conditions.

PMID- 19166375
TI  - Umbilical cord blood used to build human heart valves in laboratory.

PMID- 19166379
TI  - Introduction to facilitated synthesis.

PMID- 19166380
TI  - Regulation of airway innate and adaptive immune responses: the IL-17 paradigm.
AB  - IL-17 is a proinflammatory cytokine produced by immune cells. Its significance in
      host defense and disease development has been demonstrated in various infection
      and autoimmune models. Recently, additional studies have shown that IL-17 is also
      important in modulating airway immune response in several aspects. Along with the
      well-established Th1/Th2 model, new discoveries regarding the Th17 lineage and IL
      17 functions have added an extra twist to the already complicated cytokine
      network that regulates airway immunity. The IL-17 receptor is expressed on blood
      cells, as well as on structural cells such as the epithelial cells in the airway.
      Therefore, the effect of IL-17 on airway immunity is very broad, covering both
      the innate and the adaptive aspects. In this review, we summarize the findings of
      recent studies on IL-17 signaling and function in pulmonary immune response, and
      the implications of IL-17 in disease pathogenesis.

PMID- 19166382
TI  - Gene therapy in type 1 diabetes.
AB  - Type 1 diabetes (T1D) is caused by the autoimmune-mediated destruction of insulin
      producing beta cells in the pancreas. T1D affects as many as 3 million patients
      in the United States alone, with 15,000 new cases developing every year (Juvenile
      Diabetes Research Foundation), and presently there is no cure for T1D. In recent
      years, there has been a great deal of interest in developing gene therapy
      approaches to treat T1D. Gene therapy approaches tend to fall into three broad
      categoriesthose aimed at preventing or curing autoimmunity, those aimed at
      restoring insulin production through islet transplant or genetically engineered
      insulin production, and approaches that aim to prevent the morbidity and
      mortality associated with this complex disease. We review these studies here.

PMID- 19166383
TI  - IL-7 and IL-15: biology and roles in T-Cell immunity in health and disease.
AB  - Cytokines IL-7 and IL-15 are essentially involved in T-cell homeostasis. IL-7 is
      required for developing mature T cells in the thymus, whereas in the periphery,
      it promotes the survival of naive and memory T cells by upregulating the
      antiapoptotic molecule Bcl-2. IL-15 potently induces the proliferation of memory
      CD8+ T cells independently of antigen and augments their effector function.
      Although IL-7 and IL-15 may help to defend the host against microorganisms and
      tumors by promoting T-cell immunity, dysregulated production of IL-7 and IL-15
      can be harmful. In fact, increased levels of IL-15 in the circulation and
      inflamed tissues have been reported in various autoimmune diseases, including
      rheumatoid arthritis (RA), possibly contributing to the pathogenesis. In
      addition, IL-7, which may induce the production of inflammatory cytokines from T
      cells and monocytes, are found to be elevated in the joints of patients with RA.
      Here, we review what is currently known about the roles of these cytokines in T
      cell immunity, in general, as well as in RA, in particular, focusing on recent
      discoveries.

PMID- 19166381
TI  - Understanding how lipopolysaccharide impacts CD4 T-cell immunity.
AB  - Lipopolysaccharide (LPS) is a natural adjuvant synthesized by gram-negative
      bacteria that has profound effects on CD4 T-cell responses. LPS stimulates cells
      through the Toll-like receptor 4 (TLR4), causing the release of inflammatory
      cytokines and upregulation of costimulatory molecules on antigen-presenting cells
      (APCs). The combination of signals from antigens, costimulation, and cytokines
      allows CD4 T cells to overcome suppressive barriers and accumulate in large
      numbers. T cells that are primed in an LPS-stimulated environment are programmed
      for long-term survival following clonal expansion. LPS is well-known for
      generating Th1 responses. However, under appropriate conditions it can also
      support differentiation into other T-helper lineages, demonstrating its
      pleiotropic nature. Although molecular analyses have provided insights into how
      immune responses are controlled by LPS in vivo, its powerful adjuvant activity is
      also associated with toxicity. Research on partial TLR4 agonists such as
      monophosphoryl lipid A have demonstrated that toxicity and immunogenicity are not
      always linked, making them useful candidates for human vaccines. In this sense,
      many years of LPS research have ultimately contributed to vaccine design, and the
      next generation may involve studying how the balance between different CD4 T-cell
      subsets is controlled.

PMID- 19166384
TI  - Peritoneal B-cell subsets in the genus Mus: their role in innate immunity.
AB  - In this review, we demonstrate that wild-derived mouse strains (wild-DMS)
      represent a useful tool for dissecting the immune system. We confirm and extend
      the notion that we and others have previously advanced, which is that common
      laboratory mice are not fully representative of the whole genus Mus. We
      illustrate how wild-DMS helped us to unveil a novel B-cell population that, in
      contrast to the B-1 cell population, is present in the entire genus Mus,
      including common laboratory mice. Moreover, we suggest that Bw cells belong to
      the "natural memory" B-cell population that comprises B-1 and MZ B cells.

PMID- 19166385
TI  - New concepts on the pathogenesis of autoimmune diseases: a role for immune
      homeostasis, immunoregulation, and immunosenescence.
AB  - Complex autoimmune diseases are chronic conditions initiated by a loss of
      immunological tolerance to self-antigens. Despite many years of intense
      investigation, the etiopathogenic mechanisms initiating these chronic
      inflammatory conditions remain undefined. The relatively high prevalence and the
      clustering of multiple autoimmune diseases within individuals or within families
      suggest that rather common immune mechanisms may facilitate the development of
      autoimmune diseases. However, specific genetic or environmental factors seem to
      be necessary for triggering disease. Clearly, immune mechanisms, which are
      intended to protect from disease, fail or become dysregulatcd. In this review, we
      discuss the mechanisms of immune homeostasis, immune regulation, and
      immunosenescence. We focus on the merit, consequences, and/or shortcomings of
      these mechanisms and speculate on their possible involvement in autoimmune
      disease development.

PMID- 19166387
TI  - Role of innate immunity in transplantation tolerance.
AB  - Allogeneic organ transplantation has proven to be an effective therapeutic
      strategy for patients with end-stage organ disease. However, the chronic
      immunosuppression that is required for the survival of the allograft increases
      the risk for infection and malignancy. The establishment of transplantation
      tolerance, defined functionally as the survival of a donor allograft in the
      absence of immunosuppression, is the ultimate goal in the field of
      transplantation. Transplantation tolerance can be achieved using approaches that
      induce peripheral and/or central tolerance to the allograft. Protocols based on
      costimulation blockade (CB) have emerged as some of the most promising protocols
      for inducing long-term allograft survival in the absence of chronic
      immunosuppression. Despite its potential, recent evidence suggests that the
      efficacy of costimulation blockade can be reduced by environmental perturbations
      such as infection or inflammation, which activate Toll-like receptors (TLR). In
      this review, we discuss how the activation of TLRs can affect the induction and
      maintenance of transplantation tolerance.

PMID- 19166388
TI  - Development and functional properties of thymic and extrathymic T lymphocytes.
AB  - Although vertebrate hematopoiesis is known to occur in a variety of locations,
      the differentiation of T lymphocytes takes place only in the thymus. Conversely,
      the only known function of the thymus is to produce T lymphocytes. As thymic
      function progressively diminishes with age in all individuals, and decreased
      thymic capacity has been linked to an impaired resistance to infections and
      cancer, increasing thymic function and/or extrathymic T-cell development could
      thus play an important role in health management in elderly subjects. However, it
      is currently unclear why the thymus is essential for T-cell development and
      precisely what is necessary to make a functional T lymphopoietic organ. In this
      review, we shall discuss the current literature on the similarities and
      differences between thymic and extrathymic T cells. A major conclusion is that
      innate T cells can be generated extrathymically, but only the thymus can support
      the development of classic adaptive T cells. Functional differences between
      thymic and extrathymic T cells provide a rationale for conservation of the thymus
      as the sole primary T lymphoid organ. These differences also have implications
      for the management of thymus involution.

PMID- 19166386
TI  - Response of gammadelta T Cells to plant-derived tannins.
AB  - Many pharmaceutical drugs arc isolated from plants used in traditional medicines,
      and new plant-derived pharmaceutical drugs continue to be identified. Relevant to
      this review, different plant-derived agonists for gammadelta T cells are
      described that impart effector functions upon distinct subsets of these cells.
      Recently, plant tannins have been defined as one class of gammadelta T cell
      agonist and appear to preferentially activate the mucosal population. Mucosal
      gammadelta T cells function to modulate tissue immune responses and induce
      epithelium repair. Select tannins, isolated from apple peel, rapidly induce
      immune gene transcription in gammadelta T cells, leading to cytokinc production
      and increased responsiveness to secondary signals. Activity of these tannin
      preparations tracks to the procyanidin fraction, with the procyanidin trimer (C1)
      having the most robust activity defined to date. The response to the procyanidins
      is evolutionarily conserved in that responses are seen with human, bovine, and
      murine gammadelta T cells, although human cells show less selectivity.
      Procyanidin-induced responses described in this review likely account for the
      expansion of mucosal gammadelta T cells seen in mice and rats fed soluble
      extracts of tannins. Use of procyanidins to activate gammadelta T cells may
      represent a novel approach for the treatment of tissue damage and autoimmune
      diseases.

PMID- 19166389
TI  - The role of intermediate filament proteins in the development of neurological
      disease.
AB  - Intermediate filaments (IFs), along with microfilaments and microtubules,
      comprise the three intracellular filaments identified in eukaryotic cells to
      date. Together, these three distinct filamentous networks act in a dynamic and
      tightly interconnected fashion to comprise the eukaryotic cytoskeleton. As such,
      they are involved in a number of essential and diverse cellular processes,
      including division, molecular transport, and the maintenance of structural
      integrity in the face of mechanical stress. Underscoring the ubiquitous
      importance of IF proteins to the normal function of cellular systems, mutations
      in IF-encoding genes that affect the structure, function, or regulation of these
      proteins are commonly found in association with a range of heritable genetic
      diseases. The diversity of IF-related disease is indeed as wide as the
      distribution of IF proteins themselves, effecting the development of a broad
      range of disease phenotypes. Here we review, with specific reference to recent
      developments in the correlation of genotype with phenotype, how the perturbation
      of IF networks can elicit the development of human neurological disease.

PMID- 19166390
TI  - Cerebellar-dependent learning as a neurobehavioral index of the cannabinoid
      system.
AB  - Delta-9-tetrahydrocannabinol (THC) is the primary psycho-active ingredient in
      Cannabis spp., the most widely used illicit drug in the United States. THC is an
      exogenous agonist of the central cannabinoid receptor (CB1), one of the most
      abundant G-coupled receptors in the mammalian brain. Although CB1 receptors are
      distributed throughout the brain, they are found at very high levels in the
      cerebellum. Despite the variety of disturbances associated with acute cannabis
      intoxication, including altered short-term memory, dissociation of thoughts,
      motor impairments, and paranoia, among others, a reliable index of cannabinoid
      system function has in large part eluded scientists. Thus, there is a demand in
      contemporary clinical neuroscience for methods sensitive to cannabinoid system
      function, not only for assessing how cannabis use influences human information
      processing, but also to assess the involvement of the endocannabinoid system
      (ECS) in clinical disease and evaluate the effects of CB1-based drug therapies.
      The purpose of the present article, therefore, is to address this current need by
      integrating two separate literatures. The first literature demonstrates that the
      ECS mediates synaptic plasticity, specifically, long-term depression (LTD) of
      parallel fibers at the parallel fiber-Purkinje junction in the cerebellar cortex.
      The second literature suggests that LTD at this junction is necessary for the
      acquisition of the primary dependent variable in delay eyeblink conditioning
      (EBC)--the exhibition of temporally measured conditioned responses. These two
      literatures are integrated by proposing an updated EBC circuit that incorporates
      the CB1 receptor and the endogenous cannabinoids. Finally, the implications of
      the model is discussed in consideration of recent evidence from CB1 knockout
      mice, human cannabis users, and schizophrenia patients, with the expectation that
      translational research on the cannabinoid system will be advanced.

PMID- 19166391
TI  - Methylphenidate treated at the test cage--dose-dependent sensitization or
      tolerance depend on the behavioral assay used.
AB  - Methylphenidate is the drug most often used to treat attention
      deficit/hyperactivity disorder (ADHD), a common behavioral disorder of children
      and young adults. The objectives of this study are (1) to use two different
      experimental assays of measuring animal activity--the wheel-running activity and
      the computerized open field--to establish which is more sensitive to acute and
      repetitive methylphenidate (MPD) administration and (2) to determine whether
      repetitive MPD treatment elicits adverse effects such as tolerance and behavioral
      sensitization. The dose-response protocol of MPD (0.6, 2.5, and 10.0 mg/kg)
      administration was performed in three groups of animals, with an additional
      saline control group as follows: single saline injection as the control/baseline
      followed by 6 consecutive days of MPD injections (0.6, 2.5, or 10.0 mg/kg MPD), 3
      days of washout, and a day of MPD rechallenge. In general, the two different
      activity assays showed similar observations for the acute effect of MPD by
      eliciting increases in activity in a dose-dependent manner. The groups receiving
      repetitive 0.6 and 2.5 mg/kg MPD tested in the open-field assay exhibited further
      increase in activity that can be interpreted as behavioral sensitization, whereas
      the groups receiving 10 mg/kg MPD exhibited a reduction in activity, suggesting
      that tolerance was developed to the drug. All the groups (0.6, 2.5, and 10.0
      mg/kg MPD) tested following repetitive MPD in the wheel-running assay exhibited a
      further increase in their activity, for example, all the groups exhibited
      behavioral sensitization. These different observations were interpreted as
      potentially measuring different kinds of locomotor activity.

PMID- 19166392
TI  - Nanoparticle-cell interactions: drug delivery implications.
AB  - Design strategies to enhance drug delivery at specific cellular organelle by
      taking advantage of the endocytotic pathways are still in the early stages of
      development. This review provides a summary of the endocytosis machineries and
      pathways, as well as their involvement in nanoparticle internalization processes
      into either polarized epithelial cells or nonpolarized cells, in view of the
      marked differences in endocytic processes occurring within those cell types. The
      relevance of the physicochemical properties of nanoparticles upon their entry
      into the cells, as well as the experimental tools used to investigate the entry
      of nanoparticles into cells, is also addressed. The objective of this review is
      to present current information and achievements for a more in-depth comprehension
      of the internalization process and intracellular trafficking of nanoparticulate
      drug delivery systems within various cells types.

PMID- 19166393
TI  - A review of the application of lipid-based systems in systemic, dermal/
      transdermal, and ocular drug delivery.
AB  - The introduction of combinatorial chemistry and the development of high
      throughput techniques has significantly increased the amount of new active
      lipophilic molecular entities. As a result, the need for successful delivery of
      these lipophilic active compounds has also increased. One such method of delivery
      is through the use of advanced lipid-based drug delivery systems. Traditionally,
      the majority of reviews of lipid-based drug delivery systems were based on the
      oral administration field only. This review article focuses on the use of lipids
      in parenteral, dermal/ transdermal, and ocular drug delivery systems. Specific
      needs, considerations, approaches, and limitations in lipid-based drug delivery
      are discussed herein on the basis of the anatomical and physiological diversity
      of the target organs and systems.

PMID- 19166394
TI  - [The role of inflammatory factors in pathogenesis of ischemic heart disease].
AB  - PURPOSE: To study mechanisms of immune derangements in coronary heart disease
      (CHD). MATERIAL AND METHODS: We measured basic markers of immune activation in 43
      patients with CHD and NYHA I-IV class heart failure (HF). There were 41 men and 2
      women aged 33 - 64 years (mean 48 +/- 8 years). Concentrations of hsCRP, IgA,
      IgM, IgG were measured using commercially available kits. IL-8, sIL-2R, IL-6, IL
      18, IL-10, IFN-gamma endothelin levels were measured using enzyme-linked
      immunosorbent assay method. RESULTS: We found evidence of participation of
      proinflammatory factors in pathogenesis of HF and established associations of
      mediators of inflammation (CRP, IL-8) with severity of HF, endothelial
      dysfunction, and impairment of cardiac function.

PMID- 19166396
TI  - [Prognostic value of atrial fibrillation in patients--survivors of acute coronary
      syndrome].
AB  - For the study of contribution of atrial fibrillation (AF) during acute coronary
      syndrome (ACS) in long-term prognosis after clinical stabilization we examined
      453 patients admitted to Moscow hospitals and followed them for 2.07 +/- 0.48
      years. The following events were registered: fatal and nonfatal myocardial
      infarction (MI), unstable angina (UA), fatal and nonfatal stroke, death of other
      causes. At ACS onset sinus rhythm was noted in 419 (92.5%), permanent or
      persistent AF-in 16 (3.5%), attack (paroxysm) of AF - in 18 (4.0%) patients. Mean
      length of life before end point was 884.9 +/- 23.4, 827.3 +/- 123.3 and 514.0 +/-
      111.3 days in patients with sinus rhythm, permanent/persistent AF, and attack of
      AF during first 10 days of ACS, respectively (p<0.001). Compared with patients in
      sinus rhythm in patients with attack of AF relative risk (RR) of occurrence of
      any end point was 1.75 (95% confidence interval [CI] 1.284 to 2.873, p< 0.001),
      of fatal MI - 1.72 (95% CI 1.026 to 2.873, p=0.040), of UA - 2.116 (95% CI 1.249
      to 3.585, p=0.005), of stroke - 2.863 (95% CI 1.300 to 6.301, p=0.009).
      Multifactorial analysis selected history of MI and attack of AF during first 10
      days of ACS as independent predictors of unfavorable outcome. Thus paroxysmal
      form of AF during hospital stay because of ACS is associated with higher
      probability of development of unfavorable events in the next 1-2 years.

PMID- 19166395
TI  - [Assessment of the course of ischemic heart disease after placement of stents
      with drug covering and uncovered metal stents: data of 3 years follow-up].
AB  - The placement of sirolimus-eluting stents decreases the frequency of repeat
      revascularization procedures in patients undergoing percutaneous coronary
      intervention (PCI) in randomized clinical trials. However, there is uncertainty
      about the effectiveness of sirolimus-eluting stents, and increasing concern about
      their safety in routine clinical practice. From the prof. Samko PCI laboratory in
      Moscow, Russia, we identified 426 patients, who received either bare-metal stents
      alone or sirolimus-eluting stents alone during an index PCI procedure between
      March 1, 2002, and September 31, 2004.The primary outcomes of the study were the
      rates of target-lesion revascularization, myocardial infarction, death, late
      stent thrombosis. The 3-year rate of target-lesion revascularization was
      significantly lower among patients who received sirolimus-eluting stents than
      among those who received bare-metal stents (3.1% vs. 19 %, p=0.001). The 3-year
      mortality rate was not different between the bare-metal stent group and the
      sirolimus eluting stent group (5.9% vs. 7.2%, p=0.68), the 3-year rate of all ARC
      late stent thrombosis was similar in the two groups (5.9% and 7.2%, respectively;
      p=0.95). Sirolimus-eluting stents are effective in reducing the need for target
      vessel revascularization without significantly increased rates of death, late
      stent thrombosis, myocardial infarction.

PMID- 19166397
TI  - [Myocardial infarction and depression: clinical-functional relationships and
      possibilities of correction of left ventricular remodeling with antidepressant
      tianeptine].

PMID- 19166398
TI  - [The use of felodipine in ambulatory practice: assessment of clinical efficacy
      and compliance in patients with arterial hypertension].

PMID- 19166399
TI  - [Admission and predischarge levels of NT pre brain natriuretic peptide in
      patients hospitalized because of worsening heart failure. relation to risk of
      death in the next 6-12 months].
AB  - Inhospital treatment of patients with heart failure (HF) can cause changes of N
      terminal pro-brain natriuretic peptide (NT proBNP) levels. It has not been
      established yet which NT proBNP value (before or at height of treatment
      activation) is closer related to prognosis of unfavorable outcome after
      discharge. AIM: To compare relation to risk of post discharge unfavorable outcome
      of patients with HF of NT proBNP levels measured close to hospital admission and
      discharge. MATERIAL AND METHODS: We studied 69 patients (64% men) aged 66.6 +/-
      11.0 years with coronary heart disease or hypertension hospitalized because of
      worsening HF. Median left ventricular ejection fraction was 28%. NT-proBNP was
      measured during first 3 days of hospitalization (admission level) and in 2 weeks
      after first measurement (predischarge level). Duration of follow-up was 6-12
      (mean 11.6 +/- 1.3) months. RESULTS: Admission NT-proBNP level (median 13.23,
      interquartile range 5.95-25.89 ng/ml) exceeded upper limit of normal (ULN) in 67
      patients (97.1%). Predischarge NT-proBNP became significantly lower (median 6.02
      ng/ml, interquartile range 2.52-12.23 ng/ml; p=0.012), but remained above ULN in
      62 patients (89.8%). During follow-up 27 patients (39.1%) died. Median NT-proBNP
      in the group of patients who later died compared with those who survived was
      insignificantly higher at admission (15.03 vs. 9.9 ng/ml, respectively, p=0.09)
      and significantly higher at predischarge (8.65 vs. 3.60 ng/ml, respectively,
      p=0.012). Analysis of receiver operating characteristic curves identified
      predischarge NT-proBNP level 3.5 ng/ml as cut - off value for increased risk of
      death. Multivariate regression analysis selected predischarge NT-proBNP more or
      equal 3.5 ng/ml as independent predictor of death during follow-up. CONCLUSION:
      In this group of patients hospitalized because of worsening HF predischarge but
      not admission NT-proBNP level was independently related to risk of death during
      next 6-12 months.

PMID- 19166400
TI  - [Radiofrequency ablation of chronic atrial fibrillation by combined isolation of
      pulmonary veins and anatomical modification of arrhythmia substrate].
AB  - Primary procedure of radiofrequency ablation (RFA) of chronic atrial fibrillation
      (AF) using nonfluoroscopic mapping system was carried out in 49 patients (mean
      age 52.2 +/- 11.3 years, 6 women). Etiology of AF was coronary artery disease,
      cardiosclerosis after myocarditis, dilated cardiomyopathy in 32, 11 and 2
      patients, respectively. AF was idiopathic in 4 patients. History of chronic AF
      varied from 6 months to 17 years (mean 1.8 years). During follow-up for 14 +/- 5
      months total efficacy of RFA was 86%. Redo procedures of endocardial
      electrophysiological study EPS and RFA were performed in 3 cases because of
      atypical atrial flutter in 2, 3, and 6 months after initial intervention, and in
      1 case because of focal left atrial tachycardia (2 months after initial procedure
      of EPS and RFA for AF). After repetitive sessions because of atypical atrial
      flutter and focal left atrial tachycardia efficacy was 98%. There were no
      complications related to the operations.

PMID- 19166401
TI  - [The study of effects of a novel acetylcholinesterase inhibitor on electrical
      activity of the heart].
AB  - We have investigated effect of a representative of the novel class of selective
      acetylcholinesterase inhibitors A 1,3-bis[5(diethyl-o-nitrobenzyl ammonio)
      penthyl]-6-methyluracildibromide (compound 547) on duration and rhythm of
      sequence of right atrial action potential (AP) as well as on kinetics of
      acetylcholinesterase catalyzed reaction in homogenates of skeletal muscle (m.
      extensor digitorum longus) and cardiac muscle in the rat. We have shown that
      contrary to classical acetylcholinesterase inhibitors armin and proserin none of
      studied concentrations (1, 10 and 100 nM) of compound 547 exerted significant
      effect on AP configuration and rate of sinus rhythm. Compound 547 belongs to
      noncompetitive type with K1(heart)=3.6 x 10(-4) M and K1(EDL)=1.3 x 10(-8) M.
      Proserin exerts comparable inhibitory action on reaction in the heart and
      skeletal muscle, its K1(heart)=0.73 x 10(-5) M and K1(EDL) = 0.4 x 10(-5) M. Thus
      low sensitivity of myocardium to compound 547 in electrophysiological experiments
      is not related to lesser availability of synaptic acetylcholinesterase in the
      heart compared with acetylcholinesterase in skeletal muscles but reaction
      catalyzed by cardiac acetylcholinesterase is actually to a substantial degree
      less prone to inhibition by compound 547.

PMID- 19166402
TI  - [The role of adiponectin in development and progression of cardiovascular
      diseases].
AB  - Arterial hypertension, insulin resistance, diabetes mellitus are associated with
      obesity. However exact mechanisms of this association have not been determined
      yet. Biologically active substances produced by adipose tissue participate in
      pathogenesis of cardiovascular diseases and complications. In this review we
      present data on the role of adiponectin -- adipocytokine with unique
      antiatherogenic, antiinflammatory, and insulin sensitizing properties.
      Hypoadiponectinemia is considered to be potentially modifiable cardiovascular
      risk factor and novel therapeutic target. Therapy with PPAR gamma agonists,
      blockers of renin-angiotensin and sympathetic nervous systems is associated with
      elevation of concentration of adiponectin.

PMID- 19166403
TI  - [Clinical value of the study of stiffness of arterial wall. Part I].
AB  - In this review we present concise historical background of formation of the
      interest to investigation of properties of arterial wall in this review. We
      consider in detail interrelation of arterial functions with their structure, main
      mechanisms of action of elastic properties of arteries on systemic hemodynamics.
      Definitions of terms describing structural-functional properties of arteries are
      also given. Attention is accentuated on velocity of pulse wave propagation -- an
      independent predictor of cardiovascular morbidity and mortality and generally
      accepted parameter characterizing stiffness of arterial segment. Analysis of most
      valuable factors affecting pulse wave propagation velocity and modern methods and
      devices for the study of arterial wall stiffness is presented as well.

PMID- 19166404
TI  - [The problem of classification of cardiomyopathies].

PMID- 19166405
TI  - [On the relationship between elevated salt consumption and changes of 24-hour
      arterial pressure rhythm in patients with arterial hypertension].

PMID- 19166406
TI  - [What is the optimal approach for atrial fibrillation in chronic heart failure?
      Is it rhythm control or rate control? Results of AF-CHF study].

PMID- 19166407
TI  - [Ultra low levels of low density lipoprotein cholesterol in primary prevention in
      subjects with elevated C-reactive protein. Results of JUPITER].

PMID- 19166408
TI  - [Familial hypercholesterolemia. Contemporary aspects of diagnosis, prevention,
      and therapy].

PMID- 19166409
TI  - [Diagnosis of malignant pericardial mesothelioma].
AB  - Continuing growth of rate of detection of primary tumors of the heart has been
      noted recently. Prevalence of cardiac tumors in European population according to
      data of different authors varies from 25 to 5500 cases per 1 million of
      autopsies. Malignant mesothelioma belongs to most rarely met tumors. In most
      cases pericardial malignant mesothelioma possesses high secretory capacity what
      allows to suspect tumorous process in hemorrhagic pericarditis with recurrences
      after repetitive punctures. The paper contains description of a patient with
      malignant pericardial mesothelioma. Special feature of this case has been
      atypical clinical course of the disease complicated by development of acute
      myocardial infarction of posterior left ventricular wall.

PMID- 19166411
TI  - The underuse of overuse research.

PMID- 19166413
TI  - Muc1 limits Helicobacter felis binding to gastric epithelial cells but does not
      limit colonization and gastric pathology following infection.
AB  - BACKGROUND: The mucin Muc1 is constitutively expressed by the gastric mucosa and
      is likely the first point of direct contact between the host stomach and the
      adherent pathogens. The expression of Muc1 has been shown to limit colonization
      of mice by Helicobacter pylori, known to adhere to the gastric epithelium, as
      well as associated pathology. However, the potential role of this mucin against
      nonadherent Helicobacter has not been previously studied. We therefore examined
      the importance of Muc1 on the pathogenesis of Helicobacter felis, believed not to
      adhere to the murine mucosa. METHODS AND RESULTS: Using primary cell cultures, we
      found that H. felis can bind gastric epithelial cells in vitro, and adherence to
      epithelial cells deficient in Muc1 was increased compared to controls that
      expressed the mucin. However, following infection of deficient mice, we found
      that Muc1 did not impact on H. felis colonization or pathogenesis in vivo, in
      contrast to previous observations with H. pylori. CONCLUSIONS: This demonstrates
      a variable effect of Muc1 on protection against closely related adherent and
      nonadherent Helicobacter species, and supports a key role for Muc1 in limiting
      attachment of adherent bacteria to the gastric mucosal surface.

PMID- 19166414
TI  - Systemic immunization with unadjuvanted whole Helicobacter pylori protects mice
      against heterologous challenge.
AB  - BACKGROUND: Adjuvant-free vaccines have many benefits, including decreased cost
      and toxicity. We examined the protective effect of systemic vaccination with
      adjuvant-free formalin-fixed Helicobacter pylori or bacterial lysate and the
      ability of this vaccine to induce protection against heterologous challenge.
      MATERIALS AND METHODS: Mice were vaccinated subcutaneously with H. pylori 11637
      lysate or formalin-fixed bacteria, with or without ISCOMATRIX adjuvant, then
      orally challenged with H. pylori SS1. Serum was taken prior to challenge to
      examine specific antibody levels induced by the vaccinations, and protection was
      assessed by colony-forming assay. RESULTS: Vaccination with H. pylori 11637
      lysate or formalin-fixed bacteria delivered systemically induced significantly
      higher levels of Helicobacter-specific serum IgG than the control, unvaccinated
      group and orally vaccinated group. After heterologous challenge with H. pylori
      SS1, all vaccinated groups had significantly lower levels of colonization
      compared with unvaccinated, control mice, regardless of the addition of adjuvant
      or route of delivery. Protection induced by systemic vaccination with whole
      bacterial preparations, without the addition of adjuvants, was only associated
      with a mild cellular infiltration into the gastric mucosa, with no evidence of
      atrophy. CONCLUSIONS: Subcutaneous vaccination using unadjuvanted formalin-fixed
      H. pylori has the potential to be a simple, cost-effective approach to the
      development of a Helicobacter vaccine. Importantly, this vaccine was able to
      induce protection against heterologous challenge, a factor that would be crucial
      in any human Helicobacter vaccine. Further studies are required to determine
      mechanisms of protection and to improve protective ability.

PMID- 19166415
TI  - Natural killer cell receptor T-lymphocytes in normal and Helicobacter pylori
      infected human gastric mucosa.
AB  - BACKGROUND: Helicobacter pylori infection is associated with development of
      chronic inflammation and infiltration of immune cells into the gastric mucosa. As
      unconventional T-lymphocytes expressing natural killer cell receptors are
      considered to play central roles in the immune response against infection, a
      study investigating their frequencies in normal and H. pylori-infected gastric
      mucosa was undertaken. MATERIALS AND METHODS: Flow cytometry was used to quantify
      T-cells expressing the natural killer cell markers CD161, CD56, and CD94 in
      freshly isolated lymphocytes from the epithelial and lamina propria layers of
      gastric mucosa. Thirteen H. pylori-positive and 24 H. pylori-negative individuals
      were studied. RESULTS: CD94(+) T-cells were the most abundant (up to 40%) natural
      killer receptor-positive T-cell population in epithelial and lamina propria
      layers of H. pylori-negative gastric mucosa. CD161(+) T-cells accounted for about
      one-third of all T-cells in both compartments, but the lowest proportion were of
      CD56(+) T-cells. Compared with H. pylori-negative mucosa, in H. pylori-infected
      mucosa the numbers of CD161(+) T-cells were significantly greater (p = .04) in
      the epithelium, whereas the numbers of CD56(+) T-cells were lower (p = .01) in
      the lamina propria. A minor population (< 2%) of T-cells in both mucosal layers
      of H. pylori-negative subjects were natural killer T-cells, and whose proportions
      were not significantly different (p > .05) to those in H. pylori-infected
      individuals. CONCLUSIONS: The predominance, heterogeneity, and distribution of
      natural killer cell receptor-positive T-cells at different locations within the
      gastric mucosa reflects a potential functional role during H. pylori infection
      and warrants further investigation.

PMID- 19166416
TI  - H. pylori-induced apoptosis in human gastric cancer cells mediated via the
      release of apoptosis-inducing factor from mitochondria.
AB  - BACKGROUND AND AIM: Our previous study of Helicobacter pylori-induced apoptosis
      showed the involvement of Bcl-2 family proteins and cytochrome c release from
      mitochondria. Here, we examine the release of other factors from mitochondria,
      such as apoptosis-inducing factor (AIF), and upstream events involving caspase-8
      and Bid. METHODS: Human gastric adenocarcinoma (AGS) cells were incubated with a
      cagA-positive H. pylori strain for 0, 3, 6, and 24 hours and either total protein
      or cytoplasmic, nuclear, and mitochondrial membrane fractions were collected.
      RESULTS: Proteins were immunoblotted for AIF, Bid, polyadenosine ribose
      polymerase (PARP), caspase-8, and beta-catenin. H. pylori activated caspase-8,
      caused PARP cleavage, and attenuated mitochondrial membrane potential. A time
      dependent decrease in beta-catenin protein expression was detected in cytoplasmic
      and nuclear extracts, coupled with a decrease in beta-actin. An increase in the
      cytoplasmic pool of AIF was seen as early as 3 hours after H. pylori exposure,
      and a concomitant increase was seen in nuclear AIF levels up to 6 hours. A band
      corresponding to full-length Bid was seen in both the cytoplasmic and the nuclear
      fractions of controls, but not after H. pylori exposure. Active AIF staining was
      markedly increased in gastric mucosa from infected persons, compared to
      uninfected controls. CONCLUSION: H. pylori might trigger apoptosis in AGS cells
      via interaction with death receptors in the plasma membrane, leading to the
      cleavage of procaspase-8, release of cytochrome c and AIF from mitochondria, and
      activation of subsequent downstream apoptotic events, as reported previously for
      chlorophyllin. This is consistent with AIF activation that was found in the
      gastric mucosa of humans infected with H. pylori. Hence, the balance between
      apoptosis and proliferation in these cells may be altered in response to injury
      caused by H. pylori infection, leading to an increased risk of cancer.

PMID- 19166417
TI  - IL-17 is involved in Helicobacter pylori-induced gastric inflammatory responses
      in a mouse model.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is the major cause of chronic active
      gastritis and peptic ulcer disease. Recent studies have shown that H. pylori
      produces various cytokines that are related to neutrophil or mononuclear cell
      accumulation. Interleukin-17 (IL-17) is the founding member of an emerging family
      of inflammatory cytokines whose biological activities remain incompletely
      defined. In this study, the contributions of IL-17 to the induction of gastric
      inflammation and to the protection from H. pylori infection were investigated
      using IL-17 gene-knockout (IL-17(-/-)) mice. MATERIALS AND METHODS: IL-17(-/-)and
      wild-type C57BL/6 mice were challenged with H. pylori CPY2052 (2 x 10(8) CFU/mL)
      and the histological and microbiological evaluation were carried out at specified
      times. IL-17 and myeloperoxidase (MPO) protein levels in tissues were assayed in
      duplicate using ELISA kits. RESULTS: In wild-type mice, IL-17 was undetected at
      baseline; however, the protein expression of IL-17 was induced after infection
      with H. pylori. A severe infiltration of neutrophils appeared in the submucosa
      and the lamina propria in wild-type mice. In contrast, the degree of neutrophil
      infiltration in IL-17(-/-) mice was significantly lower than that in wild-type
      mice. Although wild-type mice infected with H. pylori showed drastically higher
      MPO activity compared with uninfected wild-type mice, any significant increase in
      the enzyme activity was not revealed in infected IL-17(-/-) mice. The number of
      H. pylori colonized in the stomach of IL-17(-/-) mice was significantly lower
      than that of wild-type mice from 1 to 6 months after infection. CONCLUSIONS:
      These results suggest that IL-17 may play an important role in the inflammatory
      response to the H. pylori infection and ultimately influence the outcome of the
      H. pylori-associated disease.

PMID- 19166418
TI  - Cytotoxin-associated Gene-A-positive Helicobacter pylori strains infection
      increases the risk of recurrent atherosclerotic stroke.
AB  - BACKGROUND: CagA-positive Helicobacter pylori infection has been found to be
      associated with a first-ever atherosclerotic stroke. The aim of this study was to
      investigate whether these strains represent an independent risk factor for
      recurrent atherosclerotic stroke. MATERIALS AND METHODS: We performed a
      longitudinal study of patients with a first-ever large vessels stroke and
      resulted positive at H. pylori serology. Patients had clinical examination 1
      month after the acute event, and were subsequently visited or contacted by
      telephone up to 3 years at 6-month intervals. Sera obtained at the time of
      enrollment were frozen and analyzed for the presence of anti-CagA antibodies at
      the end of the study. The primary outcome event was any fatal or nonfatal stroke
      after the index stroke. RESULTS: One hundred seventy H. pylori-positive patients
      were included (n = 68 CagA positive and n = 102 CagA negative). No significant
      difference regarding age and other stroke risk factors was detected. According to
      Kaplan-Meier survival analysis, CagA-positive patients showed a significantly
      higher risk for stroke recurrence than CagA-negative ones (45.6% vs 17.6%; p <
      .001). Difference in the rate of recurrent stroke between the two groups
      persisted after Cox regression analysis taking into account possible confounding
      factors (hazard ratio = 3.5; 95% CI = 1.9-6.4; p < .001). CONCLUSIONS: Infection
      with H. pylori CagA-positive strains increases the risk of recurrent
      atherosclerotic stroke. Seropositivity determination should be performed in order
      to identify high-risk patients requiring a strict clinical surveillance, and the
      possible beneficial effect of eradication therapy should be evaluated.

PMID- 19166419
TI  - Effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor
      based triple therapy for Helicobacter pylori eradication: a meta-analysis.
AB  - OBJECTIVE: CYP2C19 polymorphisms have been inconsistently reported to associate
      with the efficacy of proton pump inhibitor (PPI)-based triple therapies for
      eradicating Helicobacter pylori infection. The aim of this meta-analysis was to
      determine whether CYP2C19 polymorphism affect H. pylori eradication rates
      obtained with first-line PPI-based triple therapies. METHODS: A systematic
      literature search was conducted up to July 2007 using Medline, PubMed, EMBase,
      Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science,
      CNKI (Chinese), and Wanfang (Chinese) digital database. MeSH terms and keywords
      included proton pump inhibitor, omeprazole, lansoprazole, rabeprazole,
      pantoprazole, or esomeprazole, cytochrome P4502C19 or CYP2C19, and Helicobacter
      pylori or H. pylori. Twenty articles met the inclusion criteria, and were
      included in the meta-analysis by using Review Manager 4.2.8. RESULTS: Eradication
      rates were significantly different between poor metabolizers (PM) and
      heterozygous extensive metabolizers (HetEM) (odds ratio (OR) = 1.73, p = .002)
      and between PM and homozygous extensive metabolizers (HomEM) (OR = 2.79, p <
      .0001). Moreover, eradication rates were also significant difference between
      HetEM and HomEM (OR = 2.00, p < .0001). Triple omeprazole and lansoprazole
      therapies achieved higher H. pylori eradication rates in PM than in HomEM (OR =
      4.28, p = .0005 for omeprazole and OR = 3.06, p = .001 for lansoprazole), and
      higher in HetEM than those in HomEM (OR = 3.22, p < .0001 for omeprazole and OR =
      1.95, p = .040 for lansoprazole). Rabeprazole therapies had no significant effect
      on H. pylori eradication rates (between PM and HomEM, OR = 1.35, p = .610 and
      between HetEM and HomEM, OR = 1.57, p = .190). No significant difference in H.
      pylori eradication rates between PM and HetEM was observed in the three
      individual PPI therapies. CONCLUSION: The efficacy of omeprazole- and
      lansoprazole-based first-line triple therapies at the standard doses is dependent
      on CYP2C19 genotype status, which appears not to affect the efficacy of the
      regimens including rabeprazole.

PMID- 19166420
TI  - Lafutidine versus lansoprazole in combination with clarithromycin and amoxicillin
      for one versus two weeks for Helicobacter pylori eradication in Korea.
AB  - BACKGROUND AND AIMS: Lafutidine is a novel H(2)-receptor antagonist with
      gastroprotective activity that includes enhancement of gastric mucosal blood
      flow. The aim of the present study was to test the efficacy of 7- or 14-day
      lafutidine-clarithromycin-amoxicillin therapy versus a lansoprazole-based regimen
      for Helicobacter pylori eradication. METHODS: Four hundred and sixty-three
      patients with H. pylori-infected peptic ulcer disease were randomized to one of
      four regimens: (1) lafutidine (20 mg b.i.d.), clarithromycin (500 mg b.i.d.) and
      amoxicillin (1000 mg b.i.d.) for 7 days (the 7LFT group) or (2) for 14 days (the
      14LFT group); (3) lansoprazole (30 mg b.i.d.), clarithromycin (500 mg b.i.d.),
      and amoxicillin (1000 mg b.i.d.) for 7 days (the 7LPZ group); or (4) for 14 days
      (the 14LPZ group). The eradication rates, drug compliance, and adverse effects
      among the four regimens were compared. RESULTS: The eradication rates by the
      intention-to-treat and per-protocol analyses in the 7LFT and 7LPZ groups were
      76.5% and 81.6%, and 76.9% and 82.0% (p = .94 and .95), respectively. The
      eradication rates by intention-to-treat and per-protocol analyses in the 14LFT
      and 14LPZ groups were 78.2% and 82.2%, and 80.4% and 85.9% (p = .70 and .49),
      respectively. The treatment duration for 7 days or 14 days did not affect the
      eradication rates. In addition, the adverse effect rates and discontinuation
      rates were similar among the four groups. Furthermore, the ulcer cure rate and
      symptom response rate were similar in the lafutidine and lansoprazole groups.
      CONCLUSION: The results of this study showed that lafutidine-clarithromycin
      amoxicillin therapy was a safe and effective as lansoprazole-based triple therapy
      for the eradication rate of H. pylori, and could be considered as an additional
      treatment option.

PMID- 19166421
TI  - Evaluation of two triple-therapy regimens with metronidazole or clarithromycin
      for the eradication of H. pylori infection in Vietnamese children: a randomized,
      double-blind clinical trial.
AB  - BACKGROUND: Eradication of Helicobacter pylori infection in children in
      developing countries needs further investigations upon which to base treatment
      recommendations. The aim of the study was to compare two 2-week triple therapies
      in a randomized double-blind trial. MATERIALS AND METHODS: In order not to exceed
      recommended dosages, the 238 H. pylori-infected children, aged 3 to 15 years
      (mean 8.6), were divided in two weight categories receiving at weights 13-22 kg:
      lansoprazole 15 mg once-daily and amoxicillin 500 mg twice-daily with
      metronidazole 250 mg twice-daily or clarithromycin 250 mg once-daily; at weights
      23-45 kg: lansoprazole 15 mg and amoxicillin 750 mg with metronidazole 500 mg or
      clarithromycin 250 mg, all administered twice daily. H. pylori status was
      assessed by culture and a monoclonal-based antigen-in-stool test (Premier
      Platinum HpSA PLUS) and side effects by structured questionnaires. RESULTS: The
      overall per-protocol eradication (n = 233) was similar in the two treatment
      regimens, 62.1% for the metronidazole and 54.7% for the clarithromycin-containing
      therapy. Eradication rate was higher in children >or= 23 kg (70.9%) than in
      children < 23 kg (45.7%). In children >or= 23 kg (n = 117) that received twice
      daily administration of all drugs, efficacy of the metronidazole and
      clarithromycin-containing treatments were 69.5% and 72.4%, respectively.
      CONCLUSIONS: The two treatments gave similar eradication rates. Significant
      differences for both treatments were found by weight, which could be the result
      of the once-daily proton pump inhibitor and clarithromycin and/or more antibiotic
      resistant strains in younger children.

PMID- 19166422
TI  - Clarithromycin resistance of Helicobacter pylori strains isolated from children'
      gastric antrum and fundus as assessed by fluorescent in-situ hybridization and
      culture on four-sector agar plates.
AB  - AIM: To assess validity of culture on four-sector agar plates and fluorescent in
      situ hybridization (FISH) test, and clarithromycin resistance rate in
      Helicobacter pylori strains isolated from children in the last 10 years. METHODS:
      In the last 5 years, gastric biopsy specimens from antrum and fundus were taken
      from 89 consecutive children (median age 9 years) with H. pylori gastritis and
      from 21 controls. Culture was performed on 176 gastric biopsies (89 from antrum,
      87 from fundus) on four-sector agar plates, and FISH test with DNA ProbeMix.
      After its validity was evaluated, FISH test was applied on additional 119
      biopsies from 68 children (68 from the antrum, 51 from the fundus) stored in the
      Pathology archive in the previous 5 years. RESULTS: Culture was positive in 157
      of 176 biopsies (sensitivity: 89.2%, 95% confidence interval (CI) 85-94). In 33
      of 89 children (37%) resistant strains were found in one or both gastric sites.
      FISH test was positive in 148 of 176 biopsies from infected children (sensitivity
      84.1%, 95%CI 79-89) and in none of 42 biopsies from controls (specificity 100%).
      When applied on archive biopsies, FISH test was positive in 96 of 119 (80.7%,
      95%CI 74-88). Total children harboring resistant strains in the last 10 years, as
      assessed by FISH test, were 66 of 157 (42%). Mixed infection with both sensitive
      and resistant strains were found in 40 children (25%) and in 12 of them resistant
      strains were in the fundus only. CONCLUSIONS: Culture on four-sector agar plates
      and FISH test had a high sensitivity and specificity and showed co-presence of
      sensitive and resistant strains. In one-third of children with mixed infection,
      the resistant strains were in the fundus only. Clarithromycin resistance should
      be assessed in biopsies both from the antrum and the fundus, utilizing antral
      biopsies only can underestimate its prevalence.

PMID- 19166423
TI  - Helicobacter pylori eradication therapy may facilitate gastric ulcer healing
      after endoscopic mucosal resection: a prospective randomized study.
AB  - BACKGROUND AND AIM: It remains unclear whether Helicobacter pylori eradication
      therapy affects the healing rate of iatrogenic ulcers following endoscopic
      mucosal resection (EMR) for gastric tumors. The aim of our study was to
      prospectively evaluate the effect of H. pylori eradication therapy on gastric
      ulcer healing after EMR. METHODS: After EMR, patients were randomly assigned to
      either the H. pylori eradication group (Hp group) (lansoprazole 30 mg,
      amoxicillin 1000 mg, and clarithromycin 500 mg, twice a day for 7 days) or the
      noneradication group (proton pump inhibitor, PPI group) (lansoprazole 30 mg,
      twice a day for 7 days). Four weeks after EMR, the ulcer stages and size were
      compared between the two groups. Moreover, ulcer-related symptoms, bleeding
      rates, adverse effects, and drug compliance were compared. RESULTS: A total of 64
      patients were enrolled. Of these, 17 patients were excluded from the study. The
      two groups were comparable in terms of baseline clinicopathologic
      characteristics. Four weeks after EMR, the two groups did not differ with respect
      to ulcer stage (p = .475) or ulcer-related symptoms (p = .399). However, the
      ulcer reduction ratio was significantly higher in the Hp group (0.028 +/- 0.024
      vs. 0.065 +/- 0.055, p < .05). No differences were observed between the two
      groups with regard to drug compliance, adverse drug event rates, or bleeding
      rates. CONCLUSIONS: Our results suggest that H. pylori eradication therapy might
      improve the ulcer healing rate after EMR.

PMID- 19166424
TI  - Failure of Helicobacter pylori treatment after regimes containing clarithromycin:
      new practical therapeutic options.
AB  - Failure of Helicobacter pylori treatment is a growing problem in daily practice.
      AIM: To evaluate the efficacy of two new regimes as second-line options in a
      randomized and prospective study. METHODS: Patients in whom a first eradication
      regime containing clarithromycin had failed were included. After performing
      gastroscopy and a 13C-urea breath test (UBT), the patients were randomized to
      receive a combination of 20 mg of rabeprazole, 500 mg of levofloxacin, and 200 mg
      (two tablets) of furazolidone administered once daily for 10 days (RLF) or the
      combination of 20 mg of rabeprazole, 120 mg (two tablets) of bismuth subcitrate,
      100 mg of doxycycline, and 200 mg of furazolidone, administered twice daily for
      10 days (RBDF). Clinical examinations and new UBT were performed 60 days after
      therapy. RESULTS: Sixty patients were included (mean age, 46 years, 57% females).
      Two patients were excluded: one because of adverse effects and another as a
      result of protocol violation. Compliance was similar in both groups (90% took all
      medications correctly). Side-effects (96% mild) were observed in 87% of the
      patients and were comparable between groups, except diarrhea, which was more
      frequent in group RLF (p= .025). Intention-to-treat cure rates were 77% (95%
      confidence interval (CI): 62-93%) in the RLF group and 83% (95% CI: 68-97%) in
      the RBDF group (p= .750). Per-protocol cure rates were 80% (95% CI: 65-95%) in
      the RLF group and 82% (95% CI: 67-96%) in the RBDF group (p= 1.0). CONCLUSIONS:
      Both once-daily triple (rabeprazole, levofloxacin, and furazolidone) and twice
      daily quadruple therapy (rabeprazole, bismuth subcitrate, doxycycline, and
      furazolidone) for 10 days achieved encouraging results. Subsequent studies should
      be performed to evaluate antibiotic resistance, doses, dosing intervals, duration
      of treatment, and safety of these two regimes.

PMID- 19166425
TI  - Chelation therapy is TACT-less.

PMID- 19166426
TI  - Migraine: improved outcomes in patients previously poorly responsive to therapy.

PMID- 19166427
TI  - ITAREPS relapse prevention in schizophrenia.

PMID- 19166428
TI  - A medical student perspective on interstitial cystitis: a view from the womb.

PMID- 19166429
TI  - Is healthcare in the United States too big to fail?

PMID- 19166430
TI  - Statin safety and chronic liver disease.

PMID- 19166431
TI  - A new antibiotic: lessons and perspectives.

PMID- 19166432
TI  - Understanding gastro-oesophageal reflux disease: a patient-cluster analysis.
AB  - OBJECTIVE: To determine whether patients with gastro-oesophageal reflux disease
      (GERD) can be grouped according to the physical and psychological impact of their
      disease. METHODS: In this multinational study, 7713 primary care physicians
      (PCPs) and gastrointestinal (GI) specialists took part in a structured online
      survey to determine how they perceive the clinical and psychological needs of
      their GERD patients, based on their three most recent consultations. Patients
      were grouped according to one of the five clusters that were subjectively
      developed based on preceding qualitative research. RESULTS: Findings are reported
      for 1157 respondents (875 PCPs, 282 GI specialists), who reviewed 3471 patient
      records. Two of the five original clusters were collapsed because of overlapping
      characteristics, giving rise to three patient clusters. Patients with 'long-term,
      disrupting GERD' (39%) had symptoms considered to have not only high physical but
      also psychological impact. Patients with 'recurrent, distressing GERD' (14%)
      experienced both physical and psychological impact and were worried about the
      recurrent, restrictive nature of their disease or the possibility of having a
      more serious underlying condition. Patients with 'inconveniencing GERD' (48%) had
      less frequent symptoms with overall lower impact. Overall, there was a trend for
      GI specialists to more likely see patients at higher clinical need than PCPs.
      CONCLUSIONS: Patients with GERD can generally be classified according to the
      physical and psychological impact of their disease. Recognition that such
      patients have different needs may facilitate improved management of GERD by
      allowing treatment to be tailored according to the patient's need.

PMID- 19166433
TI  - The effectiveness of esomeprazole 40 mg in patients with persistent symptoms of
      gastro-oesophageal reflux disease following treatment with a full dose proton
      pump inhibitor.
AB  - BACKGROUND: Some patients with gastro-oesophageal reflux disease (GORD) remain
      symptomatic despite proton pump inhibitor (PPI) treatment. There is a need to
      determine the most appropriate management of these patients. AIMS: To assess the
      effectiveness of esomeprazole 40 mg in GORD symptoms persisting in patients
      receiving a full daily dose PPI. METHODS: In this multi-centre open label study
      patients who had received full daily dose PPI for 8 weeks, but were still
      experiencing persistent GORD symptoms, were treated with esomeprazole 40 mg for 8
      weeks (n = 99). The primary outcome variable was the change in the frequency of
      heartburn. Patient-reported outcomes were also assessed using the Reflux Disease
      Questionnaire (RDQ) and the GORD Impact Scale (GIS). RESULTS: The mean frequency
      of heartburn was reduced by 78% from 4.4 days a week to 1 day a week at the end
      of the 8-week treatment period (p < 0.0001). Other GORD symptoms were also
      significantly reduced following of treatment with esomeprazole (all p < 0.0001).
      All RDQ dimensions and the level of symptom control as measured by the GIS also
      showed significant improvement at 8 weeks. CONCLUSIONS: In patients with
      persistent GORD symptoms despite full dose daily PPI therapy, esomeprazole 40 mg
      significantly improved the frequency and severity of all GORD symptoms.

PMID- 19166434
TI  - A comparison of glycaemic variability in CSII vs. MDI treated type 1 diabetic
      patients using CGMS.
AB  - OBJECTIVE: To evaluate and compare glucose variability, hypoglycaemic events and
      daily glycaemic control in well-controlled (HbA1c <or= 7%), type 1 diabetic
      patients treated with either continuous subcutaneous insulin infusion (CSII)
      using lispro or multiple daily insulin injection (MDI) using glargine once daily
      and lispro with meals. RESEARCH DESIGN AND METHODS: A total of 16 patients with
      type 1 diabetes receiving treatment with either CSII (eight patients) or MDI
      (eight patients), all with HbA1c levels < 7%, wore a continuous glucose
      monitoring system sensor for 3 days to compare the number, duration, timing and
      severity of hyperglycaemic and hypoglycaemic episodes. RESULTS: There were
      several more episodes of hyperglycaemic [blood glucose (BG) >or= 180 mg/dl] and
      hypoglycaemic (BG <or= 60 mg/dl) excursions observed in patients treated with
      CSII than MDI. Glycaemic exposure over 150 mg/dl was similar between the two
      groups. Maintenance of near-euglycaemia as determined by the average amount of
      time spent within the glucose range of 80-140 mg/dl was marginally significantly
      better for the MDI than for the CSII group. Although the CSII group had
      significantly more hypoglycaemic episodes below 60 mg/dl, the average duration of
      hypoglycaemia was not significantly different for the two groups. Similar
      percentages of nocturnal hypoglycaemia were seen. There were no reported major
      adverse events throughout the duration of the study. CONCLUSION: Well-controlled
      type 1 diabetic patients treated with MDI had fewer hyperglycaemic and
      hypoglycaemic excursions than patients treated with CSII.

PMID- 19166435
TI  - Non-smokers are more prone to pulmonary oedema than smokers during acute coronary
      syndrome.
AB  - OBJECTIVES: Acute coronary syndrome (ACS) patients are prone to develop pulmonary
      oedema with varied degree of hypoxaemia. The aim was to compare the risk for
      pulmonary oedema and related complications during ACS amongst non-smokers vs.
      smokers. METHODS: Prospective, observational study was performed in consecutive
      68 patients presenting with ACS. They were divided into two groups; group 1 (n =
      33) non-smokers and group 2 (n = 35) chronic smokers. Standard conservative
      treatment was given to maintain mean arterial pressure >or= 60 mmHg, oxygen
      saturation > 95%. The bedside chest x-ray was graded for Battler grading (0-4)
      for pulmonary oedema. All patients were evaluated for troponin, serial creatinine
      kinase, echocardiography, arterial blood gas, renal function and correlated with
      inotropes requirement, active respiratory support, coronary care unit (CCU) stay
      and hospital outcome. RESULTS: Patients in both the groups had similar cardiac
      involvement for cardiothoracic ratio, troponin, ejection fraction and creatinine
      kinase muscle and brain (CK-MB). The bedside chest x-ray revealed significant (p
      < 0.05) lung oedema grades (3 and 4) in 60% non-smokers (group 1) vs. smokers
      (11%). These patients (group 1) also presented with significant (p < 0.001)
      hypoxaemia (lower PaO(2)/FiO(2)-201 +/- 44), metabolic acidosis (higher lactate;
      2.1 +/- 0.72 mmol/l, base deficit; -5.1 +/- 4.8) and hypocarbia (28 +/- 2.9 mmHg)
      than smokers (group 2). The risk estimates for active respiratory support (OR
      =1.716) and inotrope use (OR = 1.836) was three times higher in non-smokers than
      smokers. CONCLUSIONS: The higher degree of pulmonary oedema and hypoxemia
      probably contributed to poor short-term outcome in non-smokers than smokers. It
      would be important to recognise and treat hypoxaemia in non-smokers during ACS.

PMID- 19166437
TI  - Screening tools to identify hospitalised elderly patients at risk of functional
      decline: a systematic review.
AB  - BACKGROUND: The elderly patient admitted to the emergency department (ED) of an
      acute care hospital is at risk of declining functionally, both during the stay at
      the hospital as an inpatient and postdischarge. Accurate and early identification
      of this population may lead to improved outcomes through targeted early
      interventions. OBJECTIVES: To identify, critically appraise and characterise
      available screening tools to screen for elderly patients at risk of functional
      decline presenting to the ED of acute care hospitals. SELECTION CRITERIA:
      Screening tools administered in the ED to identify elderly patients at risk of
      functional decline during hospital stay and/or postdischarge. All primary
      quantitative and qualitative study types were included. Population included age >
      65 years presenting to the ED of an acute care hospital. RESULTS: Six studies
      reporting on five screening tools were identified. Two instruments reported
      acceptable discriminative ability; however, one of these has not been
      prospectively validated. No studies that validated any of the instruments in a
      setting other than the development setting were identified. A single study
      reported good test-retest reliability data for one instrument, the Identification
      of Seniors at Risk. CONCLUSION: This review was unable to identify a 'gold
      standard' tool to screen for risk of functional decline for the elderly patient
      admitted to the ED. Further research should be carried out to determine
      adjunctive processes to increase the accuracy of the identification of elderly
      patients at risk of functional decline. Further research should also be carried
      out to determine the appropriateness, or generalisability of these tools in
      different healthcare settings.

PMID- 19166436
TI  - Treatment satisfaction and efficacy of the rapid release formulation of
      sumatriptan 100 mg tablets utilising an early intervention paradigm in patients
      previously unsatisfied with sumatriptan.
AB  - AIMS: To evaluate treatment satisfaction, efficacy and functional ability of the
      rapid release formulation of sumatriptan 100 mg tablets (sumatriptan RT 100 mg)
      in an early intervention paradigm in patients who were dissatisfied with low-dose
      sumatriptan and not completely satisfied with their current migraine regimen.
      METHODS: Experienced migraineurs who reported a mild migraine pain phase,
      dissatisfaction with the previous sumatriptan treatment and some dissatisfaction
      with their current treatment regimen had no experience with sumatriptan at the
      100 mg dose were enrolled in an open-label, single group study. Subjects were
      instructed to treat four migraine attacks within 30 min of the onset of mild
      pain. Treatment satisfaction was measured with the Patient Perception of Migraine
      Questionnaire Revised version (PPMQ-R) questionnaire. RESULTS: More than half of
      the subjects were either very satisfied or satisfied with the efficacy of early
      intervention sumatriptan RT 100 mg after each attack and at the follow-up study
      visit. The mean total PPMQ-R score was 75.2 out of 100. Between 63% and 73% of
      subjects were pain-free within 4 h of dosing. Between 79% and 90% of subjects
      reported an ability to function normally within 4 h of taking the study
      medication. CONCLUSION: Subjects who were previously unsatisfied with lower doses
      of sumatriptan and less than very satisfied with their current treatment regimen
      were more likely to be satisfied or very satisfied with sumatriptan RT 100 mg in
      an early intervention paradigm. Results were consistent across four migraine
      attacks and at a follow-up visit. The treatment satisfaction results corresponded
      with positive results on efficacy measures and a functional status measure.

PMID- 19166438
TI  - Inequalities in socio-economic status and invasive procedures for coronary heart
      disease: a comparison between the USA and the UK.
AB  - BACKGROUND: Coronary heart disease (CHD) is a serious health problem in the USA
      and UK. Low socio-economic status (SES) has been associated with an increased
      prevalence of CHD and also with inequalities in related health outcomes. Rates of
      utilisation of invasive coronary procedures (ICPs), which improve CHD outcomes
      and quality of life, can be employed as indicators of quality of medical care.
      OBJECTIVES: To investigate and compare inequalities in care experienced by low
      SES CHD patients in the US Medicaid programme and the UK National Health Service
      (NHS) in relation to waiting times for, and access to, ICPs. Possible ways of
      addressing SES inequalities are proposed. SETTING/SUBJECT: Coronary heart disease
      patients eligible for ICPs in the US Medicaid programme and the UK NHS. METHODS:
      A systematic literature search was performed for relevant SES inequalities. Data
      from 43 sources were analysed. RESULTS: Both countries exhibited differences in
      waiting times for coronary angiography (CA) and percutaneous transluminal
      coronary angioplasty/coronary artery bypass graft (PTCA)/(CABG). Low SES patients
      waited longer than high SES patients within each country. The disparity in CHD
      care between low and high SES patients within each country appeared to be
      similar. Low SES patients in both countries experienced reduced rates of CA and
      CABG/PTCA. IMPLICATIONS/CONCLUSION: Despite differences between the US third
      party payer system and the UK socialised, primary care-oriented system, each
      country faces the same SES inequalities regarding waiting time for and access to
      the ICPs. Understanding the reasons behind these inequalities is vital to address
      them.

PMID- 19166439
TI  - Diagnostic options for early identification and management of interstitial
      cystitis/painful bladder syndrome.
AB  - AIMS: The aims of this article were to discuss options for diagnosing
      interstitial cystitis (IC), to compare approaches and to encourage early
      diagnosis of this disorder in the primary care setting. METHODS: Experts
      discussed the tools available to diagnose IC and the advantages and disadvantages
      of each approach. Treatment options, both pharmacological and non
      pharmacological, were also discussed. The importance of patient follow-up was
      emphasised. RESULTS: Diagnostic options for IC include a thorough history and
      physical examination, laboratory evaluations, symptom screening tools, cystoscopy
      with hydrodistention, bladder biopsy, potassium sensitivity testing, intravesical
      anaesthetic challenges, urodynamics and urinary markers. Treatment options
      include oral and intravesical medications, dietary modification and physical
      therapy. Patient follow-up can be an opportunity to educate and empower patients
      to participate in their treatment. DISCUSSION: A thorough patient history,
      physical examination and laboratory evaluations are keys to the diagnosis of IC.
      Optional diagnostic approaches may help increase physician confidence in
      prescribing therapy for this disorder. Multimodal therapy with an emphasis on
      patient education can help ensure success in treating IC. CONCLUSION:
      Understanding the options available to diagnose IC may result in earlier
      identification and treatment for some patients.

PMID- 19166440
TI  - Targets and tactics: the relative importance of HbA, fasting and postprandial
      plasma glucose levels to glycaemic control in type 2 diabetes.
AB  - BACKGROUND: The incidence of type 2 diabetes is reaching pandemic proportions,
      impacting patients and healthcare systems across the globe. Evidence suggests
      that a majority of patients are not achieving recommended blood glucose targets
      resulting in an increased risk of micro- and macro-vascular complications. AIM:
      To review literature on the significance of glycosylated haemoglobin (HbA(1c)),
      fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), their inter
      relationships and relative importance in the treatment of diabetes, and to
      provide practical guidance on effective monitoring of patients. METHODS: Clinical
      guidelines on diabetes management and clinical and preclinical studies of
      glycaemic control identified through a publications database search were
      reviewed. RESULTS: Glycaemic control remains fundamental to the successful
      management of diabetes. HbA(1c) is the gold standard measure of glycaemic control
      but recent evidence suggests that postmeal hyperglycaemia also plays an important
      role in the aetiology of diabetes-associated complications and control of PPG
      levels is vital to the achievement of recommended HbA(1c) targets. CONCLUSIONS:
      The call for action on type 2 diabetes has never been more compelling; with a
      clear focus on strategies for glycaemic control, the impact of the diabetes
      pandemic can be limited.

PMID- 19166441
TI  - Guidelines on the diagnosis and treatment of pulmonary non-tuberculous
      mycobacteria infection.
AB  - While the prevalence of Mycobacterium tuberculosis continues to decline in the
      developed world, the same cannot be said for non-tuberculous mycobacteria (NTM).
      These organisms are increasing in incidence and prevalence throughout the world.
      This is probably because of a combination of increased exposure, improved
      diagnostic methods and an increase in the prevalence of risk factors that
      predispose individuals to infection. Considerable confusion can arise in
      determining in the wide range of species whether an isolated NTM is in fact a
      contaminant or a pathogenic organism when isolated in sputum or bronchoalveolar
      lavage. This confusion combined with increasing requests for advice on the
      treatment of disease has led to the development of guidelines to assist the
      clinician in diagnosing and treating infection accurately.

PMID- 19166442
TI  - Uveitis triggered by acute onset gastroenteritis.

PMID- 19166443
TI  - Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant
      in patients with primary hypercholesterolaemia or mixed dyslipidaemia.
AB  - BACKGROUND: Improving lipids beyond low-density lipoprotein cholesterol (LDL-C)
      lowering with statin monotherapy may further reduce cardiovascular risk. Niacin
      has complementary lipid-modifying efficacy to statins and cardiovascular benefit,
      but is underutilised because of flushing, mediated primarily by prostaglandin
      D(2) (PGD(2)). Laropiprant (LRPT), a PGD(2) receptor (DP1) antagonist that
      reduces niacin-induced flushing has been combined with extended-release niacin
      (ERN) into a fixed-dose tablet. METHODS AND RESULTS: Dyslipidaemic patients were
      randomised to ERN/LRPT 1 g (n = 800), ERN 1 g (n = 543) or placebo (n = 270) for
      4 weeks. Doses were doubled (2 tablets/day; i.e. 2 g for active treatments) for
      20 weeks. ERN/LRPT 2 g produced significant changes vs. placebo in LDL-C (
      18.4%), high-density lipoprotein cholesterol (HDL-C; 20.0%), LDL-C:HDL-C (
      31.2%), non-HDL-C (-19.8%), triglycerides (TG; -25.8%), apolipoprotein (Apo) B (
      18.8%), Apo A-I (6.9%), total cholesterol (TC; -8.5%), TC:HDL-C (-23.1%) and
      lipoprotein(a) (-20.8%) across weeks 12-24. ERN/LRPT produced significantly less
      flushing than ERN during initiation (week 1) and maintenance (weeks 2-24) for all
      prespecified flushing end-points (incidence, intensity and discontinuation
      because of flushing). Except for flushing, ERN/LRPT had a safety/tolerability
      profile comparable with ERN. CONCLUSION: Extended-release niacin/LRPT 2 g
      produced significant, durable improvements in multiple lipid/lipoprotein
      parameters. The improved tolerability of ERN/LRPT supports a simplified 1 g-->2 g
      dosing regimen of niacin, a therapy proven to reduce cardiovascular risk.

PMID- 19166444
TI  - Switching from NPH insulin to once-daily insulin detemir in basal-bolus-treated
      patients with diabetes mellitus: data from the European cohort of the PREDICTIVE
      study.
AB  - BACKGROUND: The PREDICTIVE study is a multinational observational study designed
      to follow up patients with diabetes who started insulin detemir (IDet) in routine
      care. Recruitment started in June 2004 and is ongoing in some countries. METHODS:
      We report 12-week follow-up data for patients with type 1 (T1D) or type 2
      diabetes (T2D) in the European cohort who, as part of basal-bolus therapy,
      switched from once- (qd) or twice-daily (bid) neutral protamine Hagedorn insulin
      (NPH) to qd IDet. End-points - evaluated from patients' records and diaries -
      were incidence of serious adverse drug reactions, glycaemic parameters,
      hypoglycaemia and weight change. RESULTS: A total of 3637 patients were included,
      n = 1500 T1D [mean age 40.9 years, body mass index (BMI) 25.0 kg/m(2),
      glycosylated haemoglobin (HbA(1c)) 7.9%] and n = 2137 T2D (mean age 60.5 years,
      BMI 31.9 kg/m(2), HbA(1c) 8.0%). IDet was well tolerated. Lower overall, major
      and nocturnal rates of hypoglycaemia were observed in T1D and T2D patients
      switching from NPH to IDet (overall, T1D: 38.2-18.56 episodes/patient year, p <
      0.001; T2D: 13.8-3.3 [corrected] episodes/patient year, p < 0.001). Switching
      from bid NPH to qd IDet resulted in significant 12-week reductions in HbA(1c)
      (T1D: -0.40%; T2D: -0.56%; both p < 0.001). Switching from qd NPH to qd IDet,
      resulted in HbA(1c) reductions of: T1D -0.52%; T2D -0.56%; both p < 0.001.
      Fasting blood glucose levels were also significantly reduced in patients with T1D
      or T2D. Overall mean weight changes were: T1D: 0.0 kg, T2D: -0.2 kg after 12
      weeks. CONCLUSION: In routine care, patients with T1D or T2D may be switched from
      NPH to IDet qd as part of a basal-bolus regimen.

PMID- 19166447
TI  - Bacteremic outcomes in older adults: what is age telling us?

PMID- 19166446
TI  - Physiological complexity underlying heart rate dynamics and frailty status in
      community-dwelling older women.
AB  - OBJECTIVES: To assess whether less physiological complexity underlying regulation
      of heart rate dynamics, as indicated by lower approximate entropy for heart rate
      (ApEn(HR)), is associated with frailty. For supporting validity, relationships
      between frailty and traditional linear indices of heart rate variability (HRV)
      were also assessed. DESIGN: Cross-sectional. SETTING: Women's Health and Aging
      Study I, a community-based observational study, 1992 to 1995. PARTICIPANTS:
      Subset of 389 community-dwelling women aged years and older with moderate to
      severe disability with ApEn(HR) data (convenience sampling). MEASUREMENTS:
      Electrocardiographic Holter recordings obtained over 2- to 3-hour periods were
      processed for ApEn(HR) and HRV measures. ApEn(HR) is a nonlinear statistic that
      quantifies the regularity of heart rate fluctuations over time. Lower ApEn(HR) is
      characteristic of heart rate time series containing a high proportion of
      repetitive patterns. Frailty was defined according to validated phenotype
      criteria. RESULTS: Median ApEn(HR) was lower in frail than in nonfrail subjects
      (P=.02). Lower ApEn(HR) (top quartile) was associated with lower likelihood of
      frailty than higher ApEn(HR) (bottom three quartiles) (odds ratio=0.47, 95%
      confidence interval=0.26-0.86), even after adjustment for major confounders.
      Frailty was consistently associated with lower HRV as assessed using time- and
      frequency-domain indices. CONCLUSION: This study supports the notion that less
      physiological complexity marks frailty and provides an empirical basis to the
      concept of frailty as a syndrome of homeostatic impairment. Future research will
      determine whether noninvasive measures of physiological complexity underlying
      heart rate dynamics might be useful for screening and monitoring of clinical
      vulnerability in older adults.

PMID- 19166448
TI  - Kounis syndrome secondary to cefuroxime-axetil use in an octogenarian.

PMID- 19166450
TI  - Despite guidelines, some elderly people receive more than one dose of
      pneumococcal vaccine.

PMID- 19166449
TI  - Association between seroprevalence of human metapneumovirus and C-reactive
      protein level and apolipoprotein E-epsilon4 allele in elderly inpatients in
      Japan.

PMID- 19166451
TI  - Studying inflammatory markers and their relationship with coronary risk factors
      in elderly egyptian people with diabetes mellitus.

PMID- 19166452
TI  - Is Charles Bonnet syndrome an early stage of dementia with Lewy bodies?

PMID- 19166453
TI  - Contemporary outcome of cardiac catheterization in nonogenarians.

PMID- 19166454
TI  - Effects of antioxidant supplements combined with resistance exercise on gains in
      fat-free mass in healthy elderly subjects: a pilot study.

PMID- 19166455
TI  - Interrelationships between leptin resistance, body composition, and aging in
      elderly women.

PMID- 19166456
TI  - Unhealthy alcohol consumption among older adults.

PMID- 19166457
TI  - Extension of the life span in patients with Werner syndrome.

PMID- 19166458
TI  - Oral health problems and quality of life: a comment.

PMID- 19166459
TI  - Seniors' perceptions of using hip protectors to reduce fracture risk.

PMID- 19166460
TI  - Evidence for fall prevention in hospitals.

PMID- 19166462
TI  - Interventions for preventing falls in acute and chronic care hospitals: a
      systematic review and meta-analysis.

PMID- 19166464
TI  - Live longer or die happier and inexpensively?

PMID- 19166465
TI  - Geriatric medical consultation is associated with less prescription of
      potentially inappropriate medications.

PMID- 19166466
TI  - Greater emotional and social effect of urinary incontinence in men than women.

PMID- 19166469
TI  - The fascia of the limbs and back--a review.
AB  - Although fasciae have long interested clinicians in a multitude of different
      clinical and paramedical disciplines, there have been few attempts to unite the
      ensuing diverse literature into a single review. The current article gives an
      anatomical perspective that extends from the gross to the molecular level. For
      expediency, it deals only with fascia in the limbs and back. Particular focus is
      directed towards deep fascia and thus consideration is given to structures such
      as the fascia lata, thoracolumbar fascia, plantar and palmar fascia, along with
      regional specializations of deep fascia such as retinacula and fibrous pulleys.
      However, equal emphasis is placed on general aspects of fascial structure and
      function, including its innervation and cellular composition. Among the many
      functions of fascia considered in detail are its ectoskeletal role (as a soft
      tissue skeleton for muscle attachments), its importance for creating osteofascial
      compartments for muscles, encouraging venous return in the lower limb,
      dissipating stress concentration at entheses and acting as a protective sheet for
      underlying structures. Emphasis is placed on recognizing the continuity of fascia
      between regions and appreciating its key role in coordinating muscular activity
      and acting as a body-wide proprioceptive organ. Such considerations far outweigh
      the significance of viewing fascia in a regional context alone.

PMID- 19166470
TI  - Heritability of human cranial dimensions: comparing the evolvability of different
      cranial regions.
AB  - Quantitative craniometrical traits have been successfully incorporated into
      population genetic methods to provide insight into human population structure.
      However, little is known about the degree of genetic and non-genetic influences
      on the phenotypic expression of functionally based traits. Many studies have
      assessed the heritability of craniofacial traits, but complex patterns of
      correlation among traits have been disregarded. This is a pitfall as the human
      skull is strongly integrated. Here we reconsider the evolutionary potential of
      craniometric traits by assessing their heritability values as well as their
      patterns of genetic and phenotypic correlation using a large pedigree-structured
      skull series from Hallstatt (Austria). The sample includes 355 complete adult
      skulls that have been analysed using 3D geometric morphometric techniques.
      Heritability estimates for 58 cranial linear distances were computed using
      maximum likelihood methods. These distances were assigned to the main functional
      and developmental regions of the skull. Results showed that the human skull has
      substantial amounts of genetic variation, and a t-test showed that there are no
      statistically significant differences among the heritabilities of facial,
      neurocranial and basal dimensions. However, skull evolvability is limited by
      complex patterns of genetic correlation. Phenotypic and genetic patterns of
      correlation are consistent but do not support traditional hypotheses of
      integration of the human shape, showing that the classification between brachy-
      and dolicephalic skulls is not grounded on the genetic level. Here we support
      previous findings in the mouse cranium and provide empirical evidence that
      covariation between the maximum widths of the main developmental regions of the
      skull is the dominant factor of integration in the human skull.

PMID- 19166471
TI  - Comparative microanatomy of the orbicularis oris muscle between chimpanzees and
      humans: evolutionary divergence of lip function.
AB  - The orbicularis oris muscle plays a role in the production of primate facial
      expressions and vocalizations, nutrient intake, and in some non-human primates it
      is used as a prehensile, manipulative tool. As the chimpanzee (Pan troglodytes)
      is the closest living relative of humans, a comparison of the orbicularis oris
      muscle between these species may increase our understanding of the morphological
      specializations related to the differing functional demands of their lips and the
      factors responsible for their divergent evolution. To this end, this study
      compares the microanatomy of the mid-line upper fibers of the orbicularis oris
      muscle between chimpanzees and humans. A mid-line portion of the orbicularis oris
      muscle was harvested from the upper lips of three chimpanzee and five human
      cadavers. The sampled blocks included the area between the lateral borders of the
      nasal alar cartilages in both species. Each sample was processed for paraffin
      histology, sectioned and stained with a variety of protocols. Sections were
      examined for fiber direction and relative thickness of muscle layers. Ratios of
      cross-sectional connective tissue area vs. cross-sectional muscle tissue area,
      muscle fiber diameter and relative dermal thickness were calculated for each
      species. In both species, a clear pars marginalis layer was recognized, contrary
      to previous reports that only humans possess this layer. In chimpanzees, the
      relative fiber diameter and relative amount of muscle tissue (i.e. based on ratio
      of connective tissue area : muscle tissue area) were significantly (P < 0.05)
      greater than in humans. In contrast, measurements of relative dermal thickness
      showed that humans have a greater average dermal thickness of the upper lip than
      chimpanzees. Taken together, these results suggest that both human and chimpanzee
      orbicularis oris muscle upper fibers meet the specific functional demands
      associated with their divergent vocal and facial display repertoires, the
      development of human speech, and the use of the upper lip as a prehensile tool in
      chimpanzees.

PMID- 19166472
TI  - The developmental clock of dental enamel: a test for the periodicity of prism
      cross-striations in modern humans and an evaluation of the most likely sources of
      error in histological studies of this kind.
AB  - Dental tissues contain regular microscopic structures believed to result from
      periodic variations in the secretion of matrix by enamel- and dentine-forming
      cells. Counts of these structures are an important tool for reconstructing the
      chronology of dental development in both modern and fossil hominids. Most studies
      rely on the periodicity of the regular cross-banding that occurs along the long
      axis of enamel prisms. These prism cross-striations are widely thought to reflect
      a circadian rhythm of enamel matrix secretion and are generally regarded as
      representing daily increments of tissue. Previously, some researchers have argued
      against the circadian periodicity of these structures and questioned their use in
      reconstructing dental development. Here we tested the periodicity of enamel cross
      striations--and the accuracy to which they can be used--in the developing
      permanent dentition of five children, excavated from a 19th century crypt in
      London, whose age-at-death was independently known. The interruption of crown
      formation by death was used to calibrate cross-striation counts. All five
      individuals produced counts that were strongly consistent with those expected
      from the independently known ages, taking into account the position of the
      neonatal line and factors of preservation. These results confirm that cross
      striations do indeed reflect a circadian rhythm in enamel matrix secretion. They
      further validate their use in reconstructing dental development and in
      determining the age-at-death of the remains of children whose dentitions are
      still forming at the time of death. Significantly they identify the most likely
      source of error and the common difficulties encountered in histological studies
      of this kind.

PMID- 19166473
TI  - Development of the mandibular condylar cartilage in human specimens of 10-15
      weeks' gestation.
AB  - This study analyses some morphological and histological aspects that could have a
      role in the development of the condylar cartilage (CC). The specimens used were
      serial sections from 49 human fetuses aged 10-15 weeks. In addition, 3D
      reconstructions of the mandibular ramus and the CC were made from four specimens.
      During weeks 10-11 of development, the vascular canals (VC) appear in the CC and
      the intramembranous ossification process begins. At the same time, in the medial
      region of the CC, chondroclasts appear adjacent to the vascular invasion and to
      the cartilage destruction. During weeks 12-13 of development, the deepest portion
      of the posterolateral vascular canal is completely surrounded by the hypertrophic
      chondrocytes. The latter emerge with an irregular layout. During week 15 of
      development, the endochondral ossification of the CC begins. Our results suggest
      that the situation of the chondroclasts, the posterolateral vascular canal and
      the irregular arrangement of the hypertrophic chondrocytes may play a notable
      role in the development of the CC.

PMID- 19166474
TI  - Mandibular corpus bone strain in goats and alpacas: implications for
      understanding the biomechanics of mandibular form in selenodont artiodactyls.
AB  - The goal of this study is to clarify the functional and biomechanical
      relationship between jaw morphology and in vivo masticatory loading in selenodont
      artiodactyls. We compare in vivo strains from the mandibular corpus of goats and
      alpacas to predicted strain patterns derived from biomechanical models for
      mandibular corpus loading during mastication. Peak shear strains in both species
      average 600-700 microepsilon on the working side and approximately 450
      microepsilon on the balancing side. Maximum principal tension in goats and
      alpacas is directed at approximately 30 degrees dorsocaudally relative to the
      long axis of the corpus on the working side and approximately perpendicular to
      the long axis on the balancing side. Strain patterns in both species indicate
      primarily torsion of the working-side corpus about the long axis and parasagittal
      bending and/or lateral transverse bending of the balancing-side corpus.
      Interpretation of the strain patterns is consistent with comparative
      biomechanical analyses of jaw morphology suggesting that in goats, the balancing
      side mandibular corpus is parasagittally bent whereas in alpacas it experiences
      lateral transverse bending. However, in light of higher working-side corpus
      strains, biomechanical explanations of mandibular form also need to consider that
      torsion influences relative corpus size and shape. Furthermore, the complex
      combination of loads that occur along the selenodont artiodactyl mandibular
      corpus during the power stroke has two implications. First, added clarification
      of these loading patterns requires in vivo approaches for elucidating
      biomechanical links between mandibular corpus morphology and masticatory loading.
      Second, morphometric approaches may be limited in their ability to accurately
      infer masticatory loading regimes of selenodont artiodactyl jaws.

PMID- 19166475
TI  - Growth of segment parameters and a morphological classification for children
      between 15 and 36 months.
AB  - This study is part of a research program that aims at a better understanding of
      the influence of individual morphological differences and physical growth on
      development of independent walking in toddlers. As morphometric and segment
      inertial parameters for toddlers aged between 15 and 36 months are indispensable
      for the mechanical analyses inherent to this purpose, parameter data were
      collected. The provided dataset of morphological and segment inertial parameters
      is a valuable tool for locomotor biomechanical modelling. Analysis of the
      parameter data showed that there are substantial changes of most segment inertial
      parameters across body length and body mass. In addition, a classification system
      was developed to categorize toddlers on the basis of morphometry, reflecting the
      segment inertial constitution of the child. A principal components analysis (PCA)
      was applied to define the variance in physique between the children. PCA resulted
      in three newly composed variables: the 'Axis of chubbiness', the 'Axis of
      allometric growth' and the 'Axis of relative limb length'. The three axes are
      plotted against each other, resulting in eight morphological classes. With this
      classification the morphotype of toddlers between 15 and 36 months can be
      specified and used for further research on their walking patterns.

PMID- 19166476
TI  - Pelvic and thigh musculature in frogs (Anura) and origin of anuran jumping
      locomotion.
AB  - Comparative analysis of the anuran pelvic and thigh musculoskeletal system
      revealed that the thigh extensors, responsible for the initial phase of jump, the
      propulsive stroke in swimming and, if used asynchronously, also for walking, are
      least affected by the transformations observed between anurans and their
      temnospondyl ancestors (as reflected in contemporary caudates). The iliac shaft
      and urostyle, two of the most important anuran apomorphies, represent skeletal
      support for muscles that are mostly protractors of the femur or are important in
      attaining a crouching position, a necessary prerequisite for rapid escape. All of
      these muscles originate or insert on the iliac shaft. As the orientation of the
      pubis, ischium and ilium is the same in anurans, caudates and by inference also
      in their temnospondyl ancestors, it is probable that the pelvis was shifted from
      the sacral vertebra posteriorly along the reduced and stiffened tail (urostyle)
      by the elongation of the illiac shaft. Thus, the original vertical orientation of
      the ilium was maintained (which is also demonstrated by stable origins of the
      glutaeus maximus, iliofemoralis and iliofibularis on the tuber superius) and the
      shaft itself is a new structure. A review of functional analysis of anuran
      locomotion suggests some clear differences from that in caudates, suggesting that
      terrestrial jumping may have been a primary locomotor activity, from which other
      types of anuran locomotion are derived.

PMID- 19166477
TI  - Cytoskeletal proteins in thymic epithelial cells of the Australian lungfish
      Neoceratodus forsteri.
AB  - The vertebrate thymus consists of distinctive subpopulations of epithelial cells
      that contain a diverse repertoire of cytoskeletal proteins. In this study of the
      thymus in the Australian lungfish, Neoceratodus forsteri, immunohistochemistry
      was used to distinguish the cytoskeletal proteins present in each class of thymic
      epithelial cell. A panel of antibodies (Abs), each specific for a different
      cytoskeletal polypeptide (keratins, vimentin, desmin, actin and tubulins), was
      used on paraffin and ultrathin resin sections of thymus. Ab AE I (reactive
      against human type I cytokeratins (CK) 14, 16 and 19) selectively stained the
      cytoplasm of capsular, trabecular and the outermost epithelial cells of Hassall's
      corpuscles. Anti-CK 10 Abs strongly labelled the capsular epithelial cells and
      less than 20% of cortical and medullary epithelial cells. The anti-50-kDa desmin
      Ab did not react with any thymic cells, whereas the anti-53-kDa desmin Ab
      labelled some capsular, cortical and medullary thymic epithelial cells. The anti
      vimentin Ab stained most of the capsular and ~60% of the cortical epithelium.
      Thymic nurse cells and Hassall's corpuscles were found to be devoid of actin,
      which was strongly detected in medullary and perivascular epithelium. Both alpha
      and beta tubulins were detected in all thymic cells. This study extends the
      concept of thymic epithelial heterogeneity. The complexity of thymic epithelium
      in N. forsteri may indicate a relationship between thymic epithelial
      subpopulations and the thymic microenvironment. These data identify anti-keratin
      Abs as a valuable tool for studying differentiation and ontogeny of the thymic
      epithelium in N. forsteri.

PMID- 19166478
TI  - Morphological and biochemical analyses of otoliths of the ice-fish Chionodraco
      hamatus confirm a common origin with red-blooded species.
AB  - The morphology and composition of the three otoliths of the Antarctic ice-fish
      Chionodraco hamatus were studied by scanning electron microscopy and X-ray
      diffraction. The composition of the sagitta, lapillus and asteriscus protein
      matrices was also analysed by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis, western blots and confocal laser scanning microscopy to reveal
      the presence of and to localize the calcium-binding proteins calmodulin,
      calbindin and S-100. Morphological results indicated that the otoliths in this
      ice-fish were similar to those of Trematomus bernacchii, a red-blooded Antarctic
      species [B. Avallone et al. (2003) J. Submicrosc. Cytol. Pathol. 35, 69-76], but
      rather different from those of other teleosts. These two Antarctic species
      possessed a completely vateritic asteriscus, whereas their sagitta and lapillus
      were made mostly of aragonite. Parallel analysis of protein patterns in C.
      hamatus and T. bernacchii revealed that the sagitta significantly differed from
      the lapillus and asteriscus in both species. The sagitta did not contain the S
      100 protein and showed calmodulin and calbindin located in discontinuous or
      incremental zones, respectively. These results demonstrate that the otoliths of
      C. hamatus and T. bernacchii share more resemblances than differences and support
      the idea of a common origin of these species.

PMID- 19166479
TI  - Ultrastructural changes of posterior lingual glands after hypoglossal denervation
      in hamsters.
AB  - Posterior lingual glands consist of two sets of minor salivary glands that serve
      important functions in oral physiology. To investigate the hypothesis that the
      hypoglossal nerve provides sympathetic innervation to the posterior lingual
      glands, we examined ultrastructural changes in the glands following hypoglossal
      denervation. In the posterior deep lingual glands (of von Ebner), the serous
      acinar cells showed a decrease in the number of secretory granules and an
      increase in lipofuscin accumulation. The ratios of cells containing lipofuscin
      granules were 11.39, 36.49 and 50.46%, respectively, of the control, 3- and 7-day
      post-axotomy glands (P < 0.001). Intraepithelial phagocytotic activity was
      increased. The mucous acinar cells in the posterior superficial lingual glands
      (of Weber) also showed degenerative changes after hypoglossal denervation. One
      week after nerve transection, marked cytoplasmic vacuolation and fragmentation of
      organelles were frequently observed. Degenerative changes were also found in
      unmyelinated axons associated with the glands. We provide the first evidence of
      the structural and functional connections between the sympathetic component of
      the hypoglossal nerve and posterior lingual glands.

PMID- 19166480
TI  - Immunocytochemical localization of MG1 mucin in human bulbourethral glands.
AB  - Salivary mucins MG1 and MG2 have been found in the oral cavity where they perform
      several functions such as the formation of the mucous layer covering the oral
      mucosa and teeth. Recent studies have demonstrated their presence in other organs
      and tissues. The aim of this study was to determine their expression in human
      bulbourethral (Cowper's) glands. Normal bulbourethral glands were obtained at
      surgery and fixed in a mixture of 1% paraformaldehyde-1.25% glutaraldehyde in 0.1
      M cacodylate buffer and embedded in Epon resin. Thin sections were labeled with
      rabbit antibodies to MG1 or to an N-terminal synthetic peptide of MG2, followed
      by gold-labeled goat anti-rabbit IgG. The granules of all mucous cells were
      intensely reactive with anti-MG1, whereas no labeling was detected for MG2. These
      results indicate that MG1 is not exclusively a salivary component and furthermore
      show that bulbourethral glands represent a significant source of the MG1 detected
      in human seminal plasma.

PMID- 19166481
TI  - Endothelial CD200 is heterogeneously distributed, regulated and involved in
      immune cell-endothelium interactions.
AB  - CD200 is a highly glycosylated cell surface protein containing two immunoglobulin
      superfamily domains in the extracellular region and performs immunosuppressive
      activities. It is widely distributed in various tissues including the vascular
      endothelium. We report here the distribution of CD200 in rat endothelia from
      different vascular beds. Endothelial CD200 immunoreactivity was weakly expressed
      in most arteries but was intensely expressed in the arterioles, most veins and
      venules, as well as continuous and fenestrated capillaries. The distribution of
      CD200 in the sinusoidal and lymphatic endothelia was variable. Immunoelectron
      microscopic studies revealed that endothelial CD200 varied considerably not only
      in different microvasculatures but also in the membrane domains at the
      subcellular level. Endothelial CD200 expression was differentially regulated by
      lipopolysaccharide in cell types both in vivo and in vitro. Functional
      assessments of endothelial CD200 suggested that the physical binding between
      CD200 and CD200 receptor (CD200R) was involved in T-cell adhesion to the
      endothelium but not in macrophage-endothelium interaction. In the latter,
      however, CD200 agonist, a synthetic peptide from complementarity-determining
      region 3 of mouse CD200, may trigger CD200R signaling in macrophages to suppress
      their adhesion to the endothelium. Our findings demonstrate that the
      distribution, subcellular localization, and lipopolysaccharide-regulation of
      endothelial CD200 are heterogeneous, and provide evidence elucidating the
      functional roles of endothelial CD200 during tissue inflammation.

PMID- 19166483
TI  - The role of caveolae and caveolin 1 in calcium handling in pacing and contraction
      of mouse intestine.
AB  - In mouse intestine, caveolae and caveolin-1 (Cav-1) are present in smooth muscle
      (responsible for executing contractions) and in interstitial cells of Cajal (ICC;
      responsible for pacing contractions). We found that a number of calcium
      handling/dependent molecules are associated with caveolae, including L-type
      Ca(2+) channels, Na(+)-Ca(2+) exchanger type 1 (NCX1), plasma membrane Ca(2+)
      pumps and neural nitric oxide synthase (nNOS), and that caveolae are close to the
      peripheral endo-sarcoplasmic reticulum (ER-SR). Also we found that this
      assemblage may account for recycling of calcium from caveolar domains to SR
      through L-type Ca (+) channels to sustain pacing and contractions. Here we test
      this hypothesis further comparing pacing and contractions under various
      conditions in longitudinal muscle of Cav-1 knockout mice (lacking caveolae) and
      in their genetic controls. We used a procedure in which pacing frequencies
      (indicative of functioning of ICC) and contraction amplitudes (indicative of
      functioning of smooth muscle) were studied in calcium-free media with 100 mM
      ethylene glycol tetra-acetic acid (EGTA). The absence of caveolae in ICC
      inhibited the ability of ICC to maintain frequencies of contraction in the
      calcium-free medium by reducing recycling of calcium from caveolar plasma
      membrane to SR when the calcium stores were initially full. This recycling to ICC
      involved primarily L-type Ca(2+) channels; i.e. pacing frequencies were enhanced
      by opening and inhibited by closing these channels. However, when these stores
      were depleted by block of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA)
      pump or calcium release was activated by carbachol, the absence of Cav-1 or
      caveolae had little or no effect. The absence of caveolae had little impact on
      contraction amplitudes, indicative of recycling of calcium to SR in smooth
      muscle. However, the absence of caveolae slowed the rate of loss of calcium from
      SR under some conditions in both ICC and smooth muscle, which may reflect the
      loss of proximity to store operated Ca channels. We found evidence that these
      channels were associated with Cav-1. These changes were all consistent with the
      hypothesis that a reduction of the extracellular calcium associated with caveolae
      in ICC of the myenteric plexus, the state of L-type Ca(2+) channels or an
      increase in the distance between caveolae and SR affected calcium handling.

PMID- 19166484
TI  - Connexin43 modulates neutrophil recruitment to the lung.
AB  - Transmigration of neutrophils through the microvascular endothelium is a cardinal
      event of acute inflammation. It has been suggested that gap junctions made of
      connexin43 (Cx43) may serve as a conducting pathway to spread inflammatory
      signals within the lung capillary network. To determine whether Cx43 contributes
      to neutrophil transmigration in vivo, the number of transmigrated neutrophils was
      monitored in lungs of Cx43 mouse models subjected to inflammation by
      intratracheal instillations of Pseudomonas aeruginosa lipopolysaccharide (LPS).
      Cx43 was detected in inflamed lungs independently of neutrophil recruitment,
      whereas Cx43 up-regulation was not detected in mice genetically protected from
      inflammation. Mice heterozygous for the Cx43 gene (gja1) showed a 56% (P < 0.01)
      reduction in airway neutrophil count. In contrast, increased (P < 0.05)
      neutrophil recruitment in response to LPS was observed in a mouse model
      expressing a mutant Cx43 with enhanced channel conductivity. In vitro adhesion
      assays showed that reduced conductivity of Cx43 channels with (43)Gap26, a Cx43
      blocking peptide, decreased adhesion of neutrophils to endothelial cells.
      Finally, we found that instillation of (43)Gap26 in inflamed lungs reduced
      neutrophil transmigration by 65% (P < 0.05). These results indicate that
      inflammatory mediators up-regulate alveolar Cx43 to promote neutrophil
      recruitment to the airspace. Cx43 may therefore represent a pharmacological
      target in lung diseases characterized by excessive neutrophil recruitment to the
      airways.

PMID- 19166488
TI  - Abnormalities occurring during female gametophyte development result in the
      diversity of abnormal embryo sacs and leads to abnormal fertilization in
      indica/japonica hybrids in rice.
AB  - Embryo sac abortion is one of the major reasons for sterility in indica/japonica
      hybrids in rice. To clarify the causal mechanism of embryo sac abortion, we
      studied the female gametophyte development in two indica/japonica hybrids via an
      eosin B staining procedure for embryo sac scanning using confocal laser scanning
      microscope. Different types of abnormalities occurred during megasporogenesis and
      megagametogenesis were demonstrated. The earliest abnormality was observed in the
      megasporocyte. A lot of the chalazal-most megaspores were degenerated before the
      mono-nucleate embryo sac stage. Disordered positioning of nucleus and abnormal
      nucellus tissue were characteristics of the abnormal female gametes from the mono
      nucleate to four-nucleate embryo sac stages. The abnormalities that occurred from
      the early stage of the eight-nucleate embryo sac development to the mature embryo
      sac stage were characterized by smaller sizes and wrinkled antipodals.
      Asynchronous nuclear migration, abnormal positioning of nucleus, and degeneration
      of egg apparatus were also found at the eight-nucleate embryo sac stage. The
      abnormalities that occurred during female gametophyte development resulted in
      five major types of abnormal embryo sacs. These abnormal embryo sacs led to
      abnormal fertilization. Hand pollination using normal pollens on the spikelets
      during anthesis showed that normal pollens could not exclude the effect of
      abnormal embryo sac on seed setting.

PMID- 19166485
TI  - Triage of women with equivocal or low-grade cervical cytology results: a meta
      analysis of the HPV test positivity rate.
AB  - Consistent evidence underlines the utility of human papillomavirus (HPV) DNA
      testing in the management of women with equivocal cervical cytological
      abnormalities, but not in case of low-grade lesions. We performed a meta-analysis
      including studies where the high-risk probe of the Hybrid Capture-II is used to
      triage these two cytological categories. The triage test-positivity rate reflects
      the colposcopy referral workload.Data were pooled on the HPV test positivity rate
      in women with atypical squamous cells of undetermined significance (ASCUS/ASC-US)
      or low-grade squamous intraepithelial lesions (LSIL), derived from different
      cytological classification systems. The meta-analysis was restricted to studies,
      published between 1991 and 2007. A random-effect model was applied for meta
      analytical pooling and the influence of covariates on the HPV positivity rate was
      analyzed by meta-regression. The variation by age was assessed within individual
      studies since age strata were not defined uniformly. On an average, 43% (95% CI:
      40-46%) of women with ASCUS/ASC-US were high-risk HPV positive (range 23-74%). In
      women with LSIL, the pooled positivity rate was 76% (95% CI: 71-81%; range 55
      89%). In spite of considerable inter-study heterogeneity, the difference in HPV
      positivity between the two triage groups was large and highly significant: 32%
      (95% CI: 27-38%). HPV rates dropped tremendously as age and cutoffs of test
      positivity increased. Other factors (cytological classification system, country,
      continent, collection method and year of publication) had no statistically
      significant impact, except in LSIL triage where HPV positivity was significantly
      lower in European compared to American studies. Women with LSIL, especially
      younger women, have high HPV positivity rates suggesting limited utility of
      reflex HPV triaging these cases. Research is needed to identify more specific
      methods to triage women with low-grade squamous cervical lesions.

PMID- 19166489
TI  - Occurrence of the transition of apical architecture and expression patterns of
      related genes during conversion of apical meristem identity in G2 pea.
AB  - G2 pea exhibits an apical senescence delaying phenotype under short-day (SD)
      conditions; however, the structural basis for its apical development is still
      largely unknown. In the present study, the apical meristem of SD-grown G2 pea
      plants underwent a transition from vegetative to indeterminate inflorescence
      meristem, but the apical meristem of long-day (LD)-grown G2 pea plants would be
      further converted to determinate floral meristem. Both SD signal and GA(3)
      treatment enhanced expression of the putative calcium transporter PPF1, and pea
      homologs of TFL1 (LF and DET), whereas LD signal suppressed their expression at
      60 d post-flowering compared with those at 40 d post-flowering. Both PPF1 and LF
      expressed at the vegetative and reproductive phases in SD-grown apical buds, but
      floral initiation obviously increased the expression level of PPF1 compared with
      the unchanged expression level of LF from 40 to 60 d post-flowering. In addition,
      although the floral initiation significantly enhanced the expression levels of
      PPF1 and DET, DET was mainly expressed after floral initiation in SD-grown apical
      buds. Therefore, the main structural difference between LD- and SD-grown apical
      meristem in G2 pea lies in whether their apical indeterminate inflorescence
      meristem could be converted to the determinate structure.

PMID- 19166490
TI  - Crossability barriers in the interspecific hybridization between Oryza sativa and
      O. meyeriana.
AB  - Oryza meyeriana Baill (GG genome) is a precious germplasm in the tertiary gene
      pool of cultivated rice (AA genome), and possesses important traits such as
      resistance and tolerance to biotic and abiotic stress. However, interspecific
      crossability barrier, a critical bottleneck restricting genes transfer from O.
      meyeriana to cultivars has led to no hybrids through conventional reproduction.
      Therefore, the reasons underlying incrossability were investigated in the present
      report. The results showed that: (i) at 3-7 d after pollination (DAP), many
      hybrid embryos degenerated at the earlier globular-shaped stage, and could not
      develop into the later pear-shaped stage. Meanwhile, free endosperm nuclei
      started to degenerate at 1 DAP, and cellular endosperm could not form at 3 DAP,
      leading to nutrition starvation for young embryo development; (ii) at 11-13 DAP,
      almost all hybrid ovaries aborted. Even though 72.22% of hybrid young embryos
      were produced in the interspecific hybridization between O. sativa and O.
      meyeriana, young embryos were not able to further develop into hybrid plantlets
      via culturing in vitro. The main reason for the incrossability was hybrid embryo
      inviability, presenting as embryo development stagnation and degeneration since 3
      DAP. Some possible approaches to overcome the crossability barriers in the
      interspecific hybridization between O. sativa and O. meyeriana are discussed.

PMID- 19166491
TI  - Determination of n+1 gamete transmission rate of trisomics and location of gene
      controlling 2n gamete formation in Chinese cabbage (Brassica rapa).
AB  - A set of trisomics of Chinese cabbage was used for determining the n+1 gamete
      transmission rate and locating the gene controlling 2n gamete formation on the
      corresponding chromosome. The results showed that the transmission rates of extra
      chromosomes in different trisomics varied from 0% to 15.38% by male gametes and
      from 0% to 17.39% by female gametes. Of the nine F(2) populations derived from
      the hybridizations between each trisomic and Bp058 (2n gamete material), only Tri
      4xBp058 showed that the segregation ratio of plants without 2n gamete formation
      to plants with 2n gamete formation was 10.38:1, which fitted the expected
      segregation ratio of the trisomics (AAa) based on the 7.37% of n+1 gamete
      transmission through female and 5.88% through male. In other populations the
      segregation ratios varied from 2.48:1 to 3.72:1, which fitted the expected 3:1
      segregation ratio of the bisomics (Aa). These results suggested that the gene
      controlling 2n gamete formation in Chinese cabbage Bp058 was located on
      chromosome 4. Further trisomic analysis based on the chromosome segregation and
      the incomplete stochastic chromatid segregation indicated that the gene locus was
      tightly linked to the centromere.

PMID- 19166492
TI  - Ectopic overexpression of wheat adenosine diphosphate-ribosylation factor, TaARF,
      increases growth rate in Arabidopsis.
AB  - Differential gene expression between hybrids and their parents is considered to
      be associated with heterosis. However, the physiological functions and possible
      contribution to heterosis of these differentially expressed genes are unknown. We
      have isolated one hybrid upregulated gene encoding putative wheat ADP
      ribosylation factor, designated TaARF. In this study, real-time quantitative
      reverse transcription-polymerase chain reaction analysis indicated that the TaARF
      transcript was preferentially expressed in root, node and crown, and the
      accumulation of TaARF mRNA in hybrid was more than 1.5-fold higher than that in
      two parents. In order to understand possible roles of the putative wheat ARF
      gene, TaARF was overexpressed in Arabidopsis, and the transgenic plants were
      characterized. We show that ectopic overexpression of TaARF in Arabidopsis leads
      to increased leaf area, increased growth rate and earlier transition to
      flowering, suggesting that TaARF plays significant roles in growth and
      development. This study provides evidence demonstrating that TaARF plays
      important roles in growth and development and we speculate that the upregulated
      expression of this gene might contribute to the heterosis observed in wheat root
      and leaf growth.

PMID- 19166493
TI  - Genetic analysis and fine mapping of two genes for grain shape and weight in
      rice.
AB  - To identify genetic loci controlling grain weight, an elite indica rice variety,
      Baodali, with large grains was identified and used in this study. Its derived
      F(2), F(3) and BC(2)F(2) with another japonica rice variety Zhonghua 11 were used
      as mapping populations. Linkage analyses demonstrated that two genes controlling
      grain weight, designated as GW3 and GW6, were mapped to chromosome 3 and
      chromosome 6, respectively. Fine mapping delimited GW3 to a 122 kb physical
      distance between two sequence tagged site markers (WGW16 and WGW19) containing 16
      open reading frames annotated by The Institute for Genomic Research
      (http://www.tigr.org). GW6 was further mapped between two simple sequence repeat
      markers (RM7179 and RM3187). These results are useful for both marker assisted
      selection of grain weight, and for further cloning of GW genes, which will
      contribute to the dissection of the molecular mechanism underlying grain weight
      in rice.

PMID- 19166494
TI  - Characters of cysteine endopeptidases in wheat endosperm during seed germination
      and subsequent seedling growth.
AB  - The endopeptidases (EPs) in wheat endosperm during seed germination and
      subsequent seedling growth were characterized by gradient-polyacrylamide gel
      electrophoresis with gelatin copolymerized into the gel. Four cysteine EPs (EP1,
      EP2, EP3 and EP4) were detected in wheat endosperm during the 7 d growth after
      seed imbibition. The results also showed that the activities of all of these EPs
      increased continuously, and EP2 first appeared and had the highest proteolytic
      activity among the four EPs in this experimental process. The optimum pH and
      temperature of all four EPs were 4.0 and 40.0 degrees C. All EPs were completely
      inhibited by 25 micromol/L E-64 and had no good thermal stabilities, especially
      EP1. In addition, these EPs had different substrate specificities to albumins,
      globulins, gliadins and glutenins; the main storage proteins of mature wheat
      endosperm. Among them, EP2 had the highest proteolytic activities on globulins,
      gliadins and glutenins, and might be the most important and specific EP with
      potential to be tightly correlated with seedling development.

PMID- 19166495
TI  - W55a encodes a novel protein kinase that is involved in multiple stress
      responses.
AB  - Protein kinases play crucial roles in response to external environment stress
      signals. A putative protein kinase, W55a, belonging to SNF1-related protein
      kinase 2 (SnRK2) subfamily, was isolated from a cDNA library of drought-treated
      wheat seedlings. The entire length of W55a was obtained using rapid amplification
      of 5' cDNA ends (5'-RACE) and reverse transcription-polymerase chain reaction(RT
      PCR). It contains a 1,029 -bp open reading frame (ORF) encoding 342 amino acids.
      The deduced amino acid sequence of W55a had eleven conserved catalytic subdomains
      and one Ser/Thr protein kinase active-site that characterize Ser/Thr protein
      kinases. Phylogenetic analysis showed that W55a was 90.38% homologous with rice
      SAPK1, a member of the SnRK2 family. Using nullisomic-tetrasomic and
      ditelocentric lines of Chinese Spring, W55a was located on chromosome 2BS.
      Expression pattern analysis revealed that W55a was upregulated by drought and
      salt, exogenous abscisic acid, salicylic acid, ethylene and methyl jasmonate, but
      was not responsive to cold stress. In addition, W55a transcripts were abundant in
      leaves, but not in roots or stems, under environmental stresses. Transgenic
      Arabidopsis plants overexpressing W55a exhibited higher tolerance to drought.
      Based on these findings, W55a encodes a novel dehydration-responsive protein
      kinase that is involved in multiple stress signal transductions.

PMID- 19166496
TI  - Response of Chinese wampee axes and maize embryos to dehydration at different
      rates.
AB  - Survival of wampee (Clausena lansiumSkeels) axes and maize (Zea mays L.) embryos
      decreased with rapid and slow dehydration. Damage of wampee axes by rapid
      dehydration was much less than by slow dehydration, and that was contrary to
      maize embryos. The malondialdehyde contents of wampee axes and maize embryos
      rapidly increased with dehydration, those of wampee axes were lower during rapid
      dehydration than during slow dehydration, and those of maize embryos were higher
      during rapid dehydration than during slow dehydration. Activities of superoxide
      dismutase (SOD), ascorbate peroxidase (APX) and catalase (CAT) of wampee axes
      markedly increased during the early phase of dehydration, and then rapidly
      decreased, and those of rapidly dehydrated axes were higher than those of slow
      dehydrated axes when they were dehydrated to low water contents. Activities of
      SOD and APX of maize embryos notable decreased with dehydration. There were
      higher SOD activities and lower APX activities of slowly dehydrated maize embryos
      compared with rapidly dehydrated maize embryos. CAT activities of maize embryos
      markedly increased during the early phase of dehydration, and then decreased, and
      those of slowly dehydrated embryos were higher than those of rapidly dehydrated
      embryos during the late phase of dehydration.

PMID- 19166497
TI  - Influence of nitrogen fertilizer and endophyte infection on ecophysiological
      parameters and mineral element content of perennial ryegrass.
AB  - An experiment was designed to determine the effect of the fungal endophyte
      Neotyphodium lolii on the growth, physiological parameters and mineral element
      content of perennial ryegrass (Lolium perennel L.), when growing at two N supply
      levels. Endophyte infection had a significant positive effect on both shoot and
      root growth of ryegrass, but this difference was only significant in the high N
      supply treatment. At high N supply, endophyte-infected (EI) plants accumulated
      more soluble sugar in the sheath and the root than endophyte-free (EF) plants.
      Endophyte infection affected mineral element concentrations in the root more than
      in the shoot. We found a significant effect of endophyte infection on B, Mn and
      Mg in the root, but significant effect was only found on B in the shoot. EI
      plants tended to accumulate less B in the shoot at both N levels, but accumulated
      more B, Mn and Mg in the root at low N levels. The difference of growth
      parameters in different periods was significant. The content of soluble sugar and
      crude protein in the sheath were also dependent on the growth stages of both EI
      and EF plants.

PMID- 19166498
TI  - Genetic identification of quantitative trait loci for contents of mineral
      nutrients in rice grain.
AB  - In present study, Fe, Zn, Mn, Cu, Ca, Mg, P and K contents of 85 introgression
      lines (ILs) derived from a cross between an elite indica cultivar Teqing and the
      wild rice (Oryza rufipogon) were measured by inductively coupled argon plasma
      (ICAP) spectrometry. Substantial variation was observed for all traits and most
      of the mineral elements were significantly positive correlated or independent
      except for Fe with Cu. A total of 31 putative quantitative trait loci (QTLs) were
      detected for these eight mineral elements by single point analysis. Wild rice (O.
      rufipogon) contributed favorable alleles for most of the QTLs (26 QTLs), and
      chromosomes 1, 9 and 12 exhibited 14 QTLs (45%) for these traits. One major
      effect of QTL for zinc content accounted for the largest proportion of phenotypic
      variation (11%-19%) was detected near the simple sequence repeats marker RM152 on
      chromosome 8. The co-locations of QTLs for some mineral elements observed in this
      mapping population suggested the relationship was at a molecular level among
      these traits and could be helpful for simultaneous improvement of these traits in
      rice grain by marker assisted selection.

PMID- 19166499
TI  - Molecular characterization of two silenced y-type genes for Glu-B1 in Triticum
      aestivum ssp. yunnanese and ssp. tibetanum.
AB  - The high molecular weight glutenin subunits (HMW-GSs) are a major class of common
      wheat storage proteins. The bread-making quality of common wheat flour is
      influenced by the composition of HMW-GSs. In the present study, two unexpressed
      1By genes from Triticum aesitvum L.ssp.yunnanese AS332 and T. aesitvum
      ssp.tibetanum AS908 were respectively cloned and characterized. The results
      indicated that both of the silenced 1By genes in AS332 and AS908 were 1By9. In
      contrast to previously reported mechanisms for silenced genes 1Ax and 1Ay, which
      was due to the insertion of transposon elements or the presence of premature stop
      codon via base substitution of C-->T transition in trinucleotides CAA or CAG, the
      silence of 1By9 genes was caused by premature stop codons via the deletion of
      base A in trinucleotide CAA, which lead to frameshift mutation and indirectly
      produced several premature stop codons (TAG) downstream of the coding sequence.

PMID- 19166500
TI  - Strategic conservation of orchard germplasm based on indigenous knowledge and
      genetic diversity: a case study of sour orange populations in China.
AB  - To effectively conserve sour orange (Citrus aurantium L.) germplasm on two
      islands at the estuary of the Yangtze River in China, we estimated genetic
      variation and relationships of the known parental trees and their proposed
      descendents (young trees) using the fingerprints of random amplified polymorphic
      DNA (RAPD). Results based on RAPD analyses showed considerable genetic diversity
      in the parental populations (H(e)=0.202). The overall populations including the
      parental and young trees showed slightly higher genetic diversity (H(e)=0.298)
      than the parents, with about 10% variation between populations. An unweighted
      pair group method with arithmetic mean analysis dendrogram based on cluster
      analysis of the Jaccard similarity among individuals demonstrated a more
      complicated relationship of the parental and young trees from the two islands,
      although the young trees showed a clear association with parental trees. This
      indicates a significant contribution of parental trees in establishing the sour
      orange populations on the two islands. According to farmers' knowledge,
      conservation of only one or two parental trees would be sufficient because they
      believed that the whole populations were generated from a single mother tree.
      However, this study suggests that preserving most parental trees and some
      selected young trees with distant genetic relationships should be an effective
      conservation strategy for sour orange germplasm on the two islands.

PMID- 19166501
TI  - Construction of a bacterial artificial chromosome library of TM-1, a standard
      line for genetics and genomics in Upland cotton.
AB  - A bacterial artificial chromosome (BAC) library was constructed for Gossypium
      hirsutum acc. TM-1, a genetic and genomic standard line for Upland cotton. The
      library consists of 147 456 clones with an average insert size of 122.8 kb
      ranging from 97 to 240 kb. About 96.0% of the clones have inserts over 100 kb.
      Therefore, this library represents theoretically 7.4 haploid genome equivalents
      based on an AD genome size of 2 425 Mb. Clones were stored in 384 384(-) well
      plates and arrayed into multiplex pools for rapid and reliable library screening.
      BAC screening was carried out by four-round polymerase chain reactions using 23
      simple sequence repeats (SSR) markers, three sequence-related amplified
      polymorphism markers and one pair of primers for a gene associated with fiber
      development to test the quality of the library. Correspondingly, in total 92
      positive BAC clones were identified with an average four positive clones per SSR
      marker, ranging from one to eight hits. Additionally, since these SSR markers
      have been localized to chromosome 12 (A12) and 26 (D12) according to the genetic
      map, these BAC clones are expected to serve as seeds for the physical mapping of
      these two homologous chromosomes, sequentially map-based cloning of quantitative
      trait loci or genes associated with important agronomic traits.

PMID- 19166502
TI  - Antagonism of 5-HT(1A) receptors uncovers an excitatory effect of SSRIs on 5-HT
      neuronal activity, an action probably mediated by 5-HT(7) receptors.
AB  - Both microdialysis and electrophysiology were used to investigate whether another
      serotonin (5-HT) receptor subtype next to the 5-HT(1A) autoreceptor is involved
      in the acute effects of a selective serotonin reuptake inhibitor on 5-HT neuronal
      activity. On the basis of a previous study, we decided to investigate the
      involvement of the 5-HT(7) receptors. Experiments were performed with the
      specific 5-HT(7) antagonist SB 258741 and the putative 5-HT(7) agonist AS19. In
      this study WAY 100.635 was used to block 5-HT(1A) receptors. Systemic
      administration of SB 258741 significantly reduced the effect of combined
      selective serotonin reuptake inhibitor and WAY 100.635 administration on
      extracellular 5-HT in the ventral hippocampus as well as 5-HT neuronal firing in
      the dorsal raphe nucleus. In the microdialysis study, co-administration of AS19
      and WAY 100.635 showed a biphasic effect on extracellular 5-HT in ventral
      hippocampus, hinting at opposed 5-HT(7) receptor mediated effects. In the
      electrophysiological experiments, systemic administration of AS19 alone displayed
      a bell-shaped dose-effect curve: moderately increasing 5-HT neuronal firing at
      lower doses while decreasing it at higher doses. SB 258741 was capable of
      blocking the effect of AS19 at a low dose. This is consistent with the
      pharmacological profile of AS19, displaying high affinity for 5-HT(7) receptors
      and moderate affinity for 5-HT(1A) receptors. The data are in support of an
      excitatory effect of selective serotonin reuptake inhibitors on 5-HT neuronal
      activity mediated by 5-HT(7) receptors. It can be speculated, that the
      restoration of 5-HT neuronal firing upon chronic antidepressant treatment, which
      is generally attributed to desensitization of 5-HT(1A) receptors alone, in fact
      results from a shift in balance between 5-HT(1A) and 5-HT(7) receptor function.

PMID- 19166503
TI  - Molecular receptive range variation among mouse odorant receptors for aliphatic
      carboxylic acids.
AB  - The ability of mammals to identify and distinguish among many thousands of
      different odorants suggests a combinatorial use of odorant receptors, with each
      receptor detecting multiple odorants and each odorant interacting with multiple
      receptors. Numerous receptors may be devoted to the sampling of particularly
      important regions of odor space. In this study, we explore the similarities and
      differences in the molecular receptive ranges of four mouse odorant receptors
      (MOR23-1, MOR31-4, MOR32-11 and MOR40-4), which have previously been identified
      as receptors for aliphatic carboxylic acids. Each receptor was expressed in
      Xenopus oocytes, along with Galpha(olf) and the cystic fibrosis transmembrane
      regulator to allow electrophysiological assay of receptor responses. We find that
      even though these receptors are relatively unrelated, there is extensive overlap
      among their receptive ranges. That is, these receptors sample a similar region of
      odor space. However, the receptive range of each receptor is unique. Thus, these
      receptors contribute to the depth of coverage of this small region of odor space.
      Such a group of receptors with overlapping, but distinct receptive ranges, may
      participate in making fine distinctions among complex mixtures of closely related
      odorant compounds.

PMID- 19166504
TI  - Role of the N-terminal alpha-helix in biogenesis of alpha7 nicotinic receptors.
AB  - We studied the role of the alpha-helix present at the N-terminus of nicotinic
      acetylcholine receptor (nAChR) subunits in the expression of functional channels.
      Deletion of this motif in alpha7 subunits abolished expression of nAChRs at the
      membrane of Xenopus oocytes. The same effect was observed upon substitution by
      homologous motifs of other ligand-gated receptors. When residues from Gln4 to
      Tyr15 were individually mutated to proline, receptor expression strongly
      decreased or was totally abolished. Equivalent substitutions to alanine were less
      harmful, suggesting that proline-induced break of the alpha-helix is responsible
      for the low expression. Steady-state levels of wild-type and mutant subunits were
      similar but the formation of pentameric receptors was impaired in the latter. In
      addition, those mutants that reached the membrane showed a slightly increased
      internalization rate. Expression of alpha7 nAChRs in neuroblastoma cells
      confirmed that mutant subunits, although stable, were unable to reach the cell
      membrane. Analogous mutations in heteromeric nAChRs (alpha3beta4 and alpha4beta2)
      and 5-HT(3A) receptors also abolished their expression at the membrane. We
      conclude that the N-terminal alpha-helix of nAChRs is an important requirement
      for receptor assembly and, therefore, for membrane expression.

PMID- 19166505
TI  - Species-dependent neuroprotection by activated protein C mutants with reduced
      anticoagulant activity.
AB  - Activated protein C (APC) is a protease with anticoagulant and cytoprotective
      activities. APC is neuroprotective in rodent models of stroke. But, an APC
      variant with reduced anticoagulant activity, 3K3A-APC, compared to wild-type APC
      shows greater neuroprotection with no risk for bleeding in stroke models. To
      determine whether 3K3A-APC exhibits species-dependent neuroprotection similar to
      that as seen with wild-type APC, we studied murine and human recombinant 3K3A-APC
      mutants which show approximately 80% reduced anticoagulant activity. Murine 3K3A
      APC (0.2 mg/kg i.v.) administered at 4 h after embolic stroke improved
      substantially functional outcome and reduced by 80% the infract volume 7 days
      after stroke. Human 3K3A-APC was neuroprotective after embolic stroke in mice,
      but at significantly higher concentrations (i.e. 2 mg/kg i.v.). Species-dependent
      neuroprotection, i.e. murine > human 3K3A-APC, was confirmed in a mouse model of
      permanent middle cerebral artery occlusion. Human 3K3A-APC had by fivefold
      greater cytoprotective activity than murine 3K3A-APC in oxygen-glucose
      deprivation model in human brain endothelial cells, whereas murine 3K3A-APC was
      by 2.5-fold more potent than human 3K3A-APC in a mouse model of NMDA-induced
      neuronal apoptosis. Thus, 3K3A-APC exhibits species-dependent neuroprotection
      which should be taken into account when designing human trials for ischemic
      stroke with APC mutants.

PMID- 19166507
TI  - Neural precursor cell cultures from GM2 gangliosidosis animal models recapitulate
      the biochemical and molecular hallmarks of the brain pathology.
AB  - In this work we showed that genotype-related patterns of hexosaminidase activity,
      isoenzyme composition, gene expression and ganglioside metabolism observed during
      embryonic and postnatal brain development are recapitulated during the
      progressive stages of neural precursor cell (NPC) differentiation to mature glia
      and neurons in vitro. Further, by comparing NPCs and their differentiated progeny
      established from Tay-Sachs (TS) and Sandhoff (SD) animal models with the wild
      type counterparts, we studied the events linking the accumulation of undegraded
      substrates to hexosaminidase activity. We showed that similarly to what observed
      in brain tissues in TS NPCs and progeny, the stored GM2 was partially converted
      by sialidase to GA2, which can be then degraded in the lysosomes to its
      components. The latter can be used in a salvage pathway for the formation of GM3.
      Interestingly, results obtained from ganglioside feeding assays and from
      measurement of lysosomal sialidase activity suggest that a similar pathway might
      work also in the SD model.

PMID- 19166508
TI  - Selectivity and functional consequences of interactions of family A G protein
      coupled receptors with neurochondrin and periplakin.
AB  - A wide range of intracellular proteins have been demonstrated to interact with
      individual G protein-coupled receptors (GPCRs) and, in certain cases, to modulate
      their function or trafficking. However, in only a few cases have the GPCR
      selectivity of such interactions been investigated. Interactions between the
      intracellular C-terminal tails of 44 GPCRs and both neurochondrin and periplakin
      were assessed in pull-down studies. 23 of these interacted with neurochondrin and
      periplakin, 10 interacted with neither whilst nine interacted with only
      neurochondrin and two with only periplakin. When appropriate GIP-interacting
      G(q)/G(11)-coupled GPCRs were expressed in cells inducibly expressing
      neurochondrin or periplakin this resulted in a reduction in the increase in
      intracellular [Ca(2+)] in response to agonist. However, induction of
      neurochondrin or periplakin was without functional consequences for GPCRs with
      which they did not interact. Unlike intracellular [Ca(2+)] signals, induction of
      expression of either interacting protein did not inhibit agonist-mediated ERK1/2
      MAPK phosphorylation. These data indicate that both periplakin and neurochondrin
      can interact with a wide range of GPCRs and modulate function selectively.
      Details of the structure of the intracellular C-terminal tail of individual
      receptors will be required to fully understand the basis of such selectivity.

PMID- 19166506
TI  - Essential roles of dopamine D4 receptors and the type 1 adenylyl cyclase in
      photic control of cyclic AMP in photoreceptor cells.
AB  - Light and dopamine regulate many physiological functions in the vertebrate
      retina. Light exposure decreases cyclic AMP formation in photoreceptor cells.
      Dopamine D(4) receptor (D(4)R) activation promotes light adaptation and
      suppresses the light-sensitive pool of cyclic AMP in photoreceptor cells. The key
      signaling pathways involved in regulating cyclic AMP in photoreceptor cells have
      not been identified. In the present study, we show that the light- and D(4)R
      signaling pathways converge on the type 1 Ca(2+)/calmodulin-stimulated adenylyl
      cyclase (AC1) to regulate cyclic AMP synthesis in photoreceptor cells. In
      addition, we present evidence that D(4)R activation tonically regulates the
      expression of AC1 in photoreceptors. In retinas of mice with targeted deletion of
      the gene (Adcy1) encoding AC1, cyclic AMP levels and Ca(2+)/calmodulin-stimulated
      adenylyl cyclase activity are markedly reduced, and cyclic AMP accumulation is
      unaffected by either light or D(4)R activation. Similarly, in mice with
      disruption of the gene (Drd4) encoding D(4)R, cyclic AMP levels in the dark
      adapted retina are significantly lower compared to wild-type retina and are
      unresponsive to light. These changes in Drd4-/- mice were accompanied by
      significantly lower Adcy1 mRNA levels in photoreceptor cells and lower
      Ca(2+)/calmodulin-stimulated adenylyl cyclase activity in retinal membranes
      compared with wild-type controls. Reduced levels of Adcy1 mRNA were also observed
      in retinas of wild-type mice treated chronically with a D(4)R antagonist, L
      745870. Thus, activation of D(4)R is required for normal expression of AC1 and
      for the regulation of its catalytic activity by light. These observations
      illustrate a novel mechanism for cross-talk between dopamine and photic signaling
      pathways regulating cyclic AMP in photoreceptor cells.

PMID- 19166509
TI  - Marked differences in cholesterol synthesis between neurons and glial cells from
      postnatal rats.
AB  - Neurons have a high demand for cholesterol to develop and maintain membrane-rich
      structures like axons, dendrites and synapses, but it remains unclear, whether
      they can satisfy their need by costly de novo synthesis. To address this, we
      compared cholesterol synthesis in serum-free cultures of highly purified CNS
      neurons and glial cells from postnatal rats. We observed marked cell-specific
      differences: Compared with glial cells, neurons showed different profiles of
      biosynthetic enzymes, post-squalene precursors and cholesterol metabolites, and
      they produced cholesterol less efficiently, possibly because of very low levels
      of lanosterol-converting enzymes. Astrocytes responded to inhibition of
      cholesterol synthesis with a much stronger up-regulation of biosynthetic enzymes
      than neurons. Our results support the idea that neurons cannot produce
      cholesterol efficiently and that they depend on an external source of this lipid.

PMID- 19166510
TI  - Pre-synaptic nicotinic and D receptors functionally interact on dopaminergic
      nerve endings of rat and mouse nucleus accumbens.
AB  - The existence of pre-synaptic auto- and hetero receptors which modulate
      neurotransmitter release is well documented. Emerging evidence show that in some
      cases these pre-synaptic receptors may also cross-talk with each other. The aim
      of the present work was to investigate whether acetylcholine receptors (nAChRs)
      and dopamine (DA) autoreceptors, which are both able to modulate DA release,
      functionally interact on the same nerve endings. We used rat and mouse nucleus
      accumbens synaptosomes pre-labeled with [(3)H]DA and exposed to nicotinic and
      dopaminergic receptor ligands. Both nicotinic agonists and 4-aminopyridine (4-AP)
      provoked [(3)H]DA release which was inhibited by quinpirole and blocked by
      sulpiride and raclopride. Both the inhibitory effect of quinpirole and the
      stimulatory effect of (-)nicotine did not change when the nAChRs or the DA
      receptors were desensitized. (-)Nicotine and 4-AP were able to stimulate [(3)H]DA
      overflow also in mouse synaptosomes and this overflow was partially inhibited by
      quinpirole. In the beta(2) knockout mice quinpirole was still able to inhibit the
      [(3)H]DA overflow elicited by 4-AP. To conclude: in rat and mouse the (-)nicotine
      evoked-release can be modulated by D(2)/D(3) autoreceptors present on the DA
      terminals and nAChRs function is independent from D(2)/D(3) autoreceptors which
      themselves may function independently from the activation of nAChRs.

PMID- 19166512
TI  - Phosphatidylinositol 3 kinase-Akt signaling serves as a circadian output in the
      retina.
AB  - The daily rhythm of L-type voltage-gated calcium channels (L-VGCCs) is part of
      the cellular mechanism underlying the circadian regulation of retina physiology
      and function. However, it is not completely understood how the circadian clock
      regulates L-VGCC current amplitudes without affecting channel gating properties.
      The phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) signaling pathway
      has been implicated in many vital cellular functions especially in trophic factor
      induced ion channel trafficking and membrane insertion. Here, we report that PI3K
      Akt signaling participates in the circadian phase-dependent modulation of L
      VGCCs. We found that there was a circadian regulation of Akt phosphorylation on
      Thr308 that peaked at night. Inhibition of PI3K or Akt significantly decreased L
      VGCC current amplitudes and the expression of membrane-bound L-VGCCalpha1D
      subunit only at night but not during the subjective day. Photoreceptors
      transfected with a dominant negative Ras had significantly less expression of
      phosphorylated Akt and L-VGCCalpha1D subunit compared with non-transfected
      photoreceptors. Interestingly, both PI3K-Akt and extracellular signal-related
      kinase were downstream of Ras, and they appeared to be parallel and equally
      important pathways to regulate L-VGCC rhythms. Inhibition of either pathway
      abolished the L-VGCC rhythm indicating that there were multiple mechanisms
      involved in the circadian regulation of L-VGCC rhythms in retina photoreceptors.

PMID- 19166513
TI  - Distinct conformational changes in activated agonist-bound and agonist-free
      glycine receptor subunits.
AB  - Ligand binding to Cys-loop receptors produces either global conformational
      changes that lead to activation or local conformational changes that do not. We
      found that the fluorescence of a fluorophore tethered to R271C in the
      extracellular M2 region of the alpha1 glycine receptor increases during glycine
      activation but not during ivermectin activation. This prompted the hypothesis
      that this signal reports a glycine-mediated conformational change not essential
      for activation. We tested this by investigating whether the fluorescence signal
      depended on whether the fluorophore was attached to a glycine-free or a glycine
      bound subunit. Agonist-free subunits were created by incorporating T204A and R65K
      mutations, which disrupted glycine binding to both (+) and (-) subunit
      interfaces. In heteromeric receptors comprising wild-type and R65K,T204A,R271C
      triple-mutant subunits, the fluorescence response exhibited a drastically reduced
      glycine sensitivity relative to the current response. Two conclusions can be
      drawn from this. First, because the labeled glycine-free subunits were activated
      by glycine binding to neighboring wild-type subunits, our results provide
      evidence for a cooperative activation mechanism. However, because the fluorescent
      label on glycine-free subunits does not reflect movements at the channel gate, we
      conclude that glycine binding also produces a local non-concerted conformational
      change that is not essential for receptor activation.

PMID- 19166511
TI  - Mutant Pink1 induces mitochondrial dysfunction in a neuronal cell model of
      Parkinson's disease by disturbing calcium flux.
AB  - Parkinson's disease (PD) is characterized by accumulation of alpha-synuclein
      (alpha-syn) and degeneration of neuronal populations in cortical and subcortical
      regions. Mitochondrial dysfunction has been considered a potential unifying
      factor in the pathogenesis of the disease. Mutations in genes linked to familial
      forms of PD, including SNCA encoding alpha-syn and Pten-induced putative kinase 1
      (PINK1), have been shown to disrupt mitochondrial activity. We investigated the
      mechanisms through which mutant Pink1 might disrupt mitochondrial function in
      neuronal cells with alpha-syn accumulation. For this purpose, a neuronal cell
      model of PD was infected with virally-delivered Pink1, and was analyzed for cell
      survival, mitochondrial activity and calcium flux. Mitochondrial morphology was
      analyzed by confocal and electron microscopy. These studies showed that mutant
      (W437X) but not wildtype Pink1 exacerbated the alterations in mitochondrial
      function promoted by mutant (A53T) alpha-syn. This effect was associated with
      increased intracellular calcium levels. Co-expression of both mutant Pink1 and
      alpha-syn led to alterations in mitochondrial structure and neurite outgrowth
      that were partially ameliorated by treatment with cyclosporine A, and completely
      restored by treatment with the mitochondrial calcium influx blocker Ruthenium
      Red, but not with other cellular calcium flux blockers. Our data suggest a role
      for mitochondrial calcium influx in the mechanisms of mitochondrial and neuronal
      dysfunction in PD. Moreover, these studies support an important function for
      Pink1 in regulating mitochondrial activity under stress conditions.

PMID- 19166515
TI  - Contactin-associated protein (Caspr) 2 interacts with carboxypeptidase E in the
      CNS.
AB  - To identify proteins interacting with the intracellular domain of the neural cell
      adhesion molecule contactin-associated protein 2 (Caspr2), yeast two-hybrid
      screening was performed. We identified carboxypeptidase E (CPE) as a Caspr2
      interacting candidate protein. Glutathione S-transferase pull-down and
      immunoprecipitation analyses indicated that Caspr2 was associated with CPE in
      vitro and in vivo. Both Caspr2 and CPE were expressed predominantly in the CNS.
      Immunohistochemical analyses revealed that both Caspr2- and CPE-like
      immunoreactivities were found to co-localize in the apical dendrites and cell
      bodies of rat cortical neurons. In subcellular localization analysis, Caspr2- and
      CPE-like immunoreactivities were co-migrated in the fractions of Golgi/ER.
      Additionally, in COS-7 cells co-transfected with CPE and Caspr2 cDNAs, Caspr2-
      and CPE-immunoreactivities were co-localized in both Golgi and membrane, whereas
      it was only observed in Golgi of either COS-7 cell transfected with CPE or Caspr2
      cDNA alone. It is known that the membrane-bound form of CPE functions as a
      sorting receptor of prohormones in the trans-Golgi network. Taken together, our
      data suggest that CPE may be a key molecule to regulate Caspr2 trafficking to the
      cell membrane.

PMID- 19166514
TI  - Nuclear respiratory factor 1 co-regulates AMPA glutamate receptor subunit 2 and
      cytochrome c oxidase: tight coupling of glutamatergic transmission and energy
      metabolism in neurons.
AB  - Neuronal activity, especially of the excitatory glutamatergic type, is highly
      dependent on energy from the oxidative pathway. We hypothesized that the coupling
      existed at the transcriptional level by having the same transcription factor to
      regulate a marker of energy metabolism, cytochrome c oxidase (COX) and an
      important subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      glutamate receptors, GluR2 (Gria2). Nuclear respiratory factor 1 (NRF-1) was a
      viable candidate because it regulates all COX subunits and potentially activates
      Gria2. By means of in silico analysis, electrophoretic mobility shift and
      supershift, chromatin immunoprecipitation, and promoter mutational assays, we
      found that NRF-1 functionally bound to Gria2 promoter. Silencing of NRF-1 with
      small interference RNA prevented the depolarization-stimulated up-regulation of
      Gria2 and COX, and over-expression of NRF-1 rescued neurons from tetrodotoxin
      induced down-regulation of Gria2 and COX transcripts. Thus, neuronal activity and
      energy metabolism are tightly coupled at the molecular level, and NRF-1 is a
      critical agent in this process.

PMID- 19166516
TI  - Editorial. Workplace environment.

PMID- 19166517
TI  - Shared governance as vertical alignment of nursing group power and nurse practice
      council effectiveness.
AB  - AIM(S): This study validates an instrument for measuring the effectiveness of
      nursing practice councils and offers a framework for measuring and understanding
      shared governance. BACKGROUND: Empowerment results from the vertical alignment of
      nursing group power with nursing unit power practices. The field lacks an
      instrument for measuring nurses' practice of power. METHOD(S): Two studies (n1 =
      119; n2 = 248) are used to validate the Nursing Practice Council effectiveness
      scale (NPCes). RESULTS: NPCes is a valid and reliable index of nursing practice
      council effectiveness. This study suggests specific diagnostic tools to
      understand two levels for actualized power, one at the group or departmental
      level and one at the unit level. CONCLUSION(S): NPCes and the Sieloff-King
      Assessment of Group Power within Organizations (SKAGPO) can be used together to
      improve examination of shared governance. Examining group power as well as unit
      level practices may give a more complete view of barriers to nurse empowerment.
      IMPLICATIONS FOR NURSING MANAGEMENT: Changing nursing power and practices in an
      organization may be made more effective by engaging and monitoring vertical
      alignment of strategies fostering power competencies among nurse leaders and
      simultaneously supporting nursing practice councils as a means of exercising
      nurse authority at the unit level.

PMID- 19166518
TI  - Nursing leadership and management effects work environments.
AB  - AIM: The aim of this literature search was to identify recent research related to
      nursing leadership and management effects on work environment using the 14 forces
      of magnetism. BACKGROUND: This article gives some historical perspective from the
      original 1983 American Academy of Nursing study through to the 2002 McClure and
      Hinshaw update to 2009 publications. EVALUATION: Research publications were given
      a priority for references. KEY ISSUES: The 14 forces of magnetism as identified
      by Unden and Monarch were: '1. Quality of leadership..., 2. Organizational
      structure..., 3. Management style..., 4. Personnel policies and programs..., 5.
      Professional models of care..., 6. Quality of care..., 7 Quality improvement...,
      8. Consultation and resources..., 9. Autonomy..., 10. Community and the
      hospital..., 11. Nurse as teacher..., 12. Image of nursing..., 13.
      Interdisciplinary relationships... and 14. Professional development....'.
      CONCLUSIONS: Correlations have been found among positive workplace management
      initiatives, style of transformational leadership and participative management;
      patient-to-nurse ratios; education levels of nurses; quality of patient care,
      patient satisfaction, employee health and well-being programmes; nurse
      satisfaction and retention of nurses; healthy workplace environments and healthy
      patients and personnel. IMPLICATIONS FOR NURSING MANAGEMENT: This article
      identifies some of the research that provides evidence for evidence-based nursing
      management and leadership practice.

PMID- 19166519
TI  - Nurses' perception of their manager's leadership style and unit climate: are
      there generational differences?
AB  - AIM: To describe and compare how nurses representing four age cohorts perceive
      their manager's leadership style and unit climate. BACKGROUND: The current
      workforce consists of nurses representing four generational cohorts. Nursing
      literature suggests that nurses from each age cohort think, behave and approach
      work differently. Limited empirical evidence, however, exists about how nurses
      from each age cohort perceive two aspects of their work environment: their
      managers' leadership style and unit climate. METHOD: This cross-sectional,
      descriptive survey was conducted using a convenience sample of 475 registered
      nurses working in different inpatient units in three community non-magnet
      hospitals. RESULTS AND CONCLUSION: Only nurses from Boomer and Gen-Xers had
      sufficient representation to be included in the data analysis. Nurses from the
      two main age cohorts did not differ in their perceptions of their manager's
      leadership style. Significant differences were found in two unit climate
      dimensions. The Gen-Xers had a less favourable perception of their unit climate
      related to warmth and belonging and administrative support. IMPLICATIONS FOR
      NURSING MANAGEMENT: Nurse manager's might reflect on how they interact with
      different age cohorts; and to involve nurses from various age cohorts in the
      development of policies to create a flexible work environment.

PMID- 19166520
TI  - The gate still swings both ways in rural Texas.
AB  - AIMS: To give nurse managers a perspective of what it is like to practice in a
      frontier or rural setting without the resources of the metropolitan centres.
      BACKGROUND: I grew up in rural Texas and more recently had the opportunity to
      work with rural hospitals seeking to be designated as Nurse Friendly by the Texas
      Nurses Association. This renewed my interest in and great respect for nurses on
      the frontier and other rural areas. KEY ISSUES: This article summarizes some
      characteristics of rural nursing in relation to their practices that address
      patient safety and quality of care, nurse satisfaction and balanced life style,
      community service, and teamwork/relationships. CONCLUSIONS: I conclude that there
      are many advantages and satisfactions in rural nursing that are different from
      but equally as meaningful and challenging as metro nursing practice. IMPLICATIONS
      FOR NURSING MANAGEMENT: This article is important because there is a shortage of
      nurses everywhere; however, direct care nurses and nurse managers in rural areas
      may have greater challenges in meeting their patient's needs while balancing
      their personal lives.

PMID- 19166521
TI  - A new practice environment measure based on the reality and experiences of nurses
      working lives.
AB  - AIMS: To explore the underlying organizational issues affecting a nurses'
      decision to leave and to develop a contemporary practice environment measure
      based on the experiences of nurses working lives. BACKGROUND: Turnover had
      reached an unacceptable level in our organization but underlying reasons for
      leaving were unknown. METHOD: In-depth interviews were conducted with 13 nurses
      who had resigned. Transcripts were analysed using the constant comparative
      method. Information from the interviews informed the development a new practice
      environment tool, which has undergone initial testing using the Content Validity
      Index and Chronbach's alpha. RESULTS: Two domains ('work life' and 'personal
      life/professional development') and five themes ('feeling safe', 'feeling
      valued', 'getting things done', 'professional development' and 'being flexible')
      emerged from the interviews. A content validity score for the new instrument was
      0.79 and Chronbach's alpha 0.93. CONCLUSION: The new practice environment tool
      has shown useful initial reliability and validity but requires wider testing in
      other settings. IMPLICATIONS FOR NURSING MANAGEMENT: The reality and experiences
      of nurses working lives can be identified through exit interviews conducted by an
      independent person. Information from such interviews is useful in identifying an
      organization's strength and weaknesses and to develop initiatives to support
      retention.

PMID- 19166522
TI  - Issues influencing psychiatric nurse retention during the first year of
      employment: a case analysis.
AB  - AIM: To explore the work experiences of psychiatric-registered nurses (RNs) that
      influence retention within the first year of employment. BACKGROUND: One
      corporation with four psychiatric inpatient facilities experienced an average RN
      turnover rate of 54% annually, with approximately 75% of new hires leaving within
      6 months of employment. METHODS: This case analysis used a grounded theory
      approach involving structured telephone interviews with 14 former and currently
      employed nurses. RESULTS: The nursing role in this organization was limited and
      task oriented, with issues involving education and training, team dynamics and
      organizational support converging to influence nurses' decisions to terminate
      employment within the first year. CONCLUSIONS: Retention of psychiatric nurses
      requires the implementation of a variety of strategies to clarify the role.
      IMPLICATIONS FOR NURSING: Nurse administrators need to review organizational
      policies and procedures to determine if current practices support the retention
      of psychiatric nurses.

PMID- 19166523
TI  - Predictors of job strain in residential dementia care nursing staff.
AB  - AIM: To identify predictors of job strain in residential nursing care staff
      working with people with dementia. BACKGROUND: It is well known that nursing
      staff experience high levels of stress, but less is known about how to predict
      job strain. METHODS: The job strain of nursing care staff (n = 344) within
      residential dementia care settings was assessed. Standard linear regression
      analysis was used to explore predictors of job strain. RESULT: Data from the
      study shows that nursing staff in residential dementia care have a demanding job
      and experience high levels of strain. The linear regression model with four
      predictor variables explained 19% of the variability in job strain scores.
      Perceived caring climate of the unit, staff education level, possibilities to
      have discussions of difficulties and ethics at work and staff age, had a
      statistically significant association with job strain. CONCLUSIONS: The caring
      climate, staff education, reflective practice and staff age can be used as
      screening variables when predicting job strain. IMPLICATIONS FOR NURSING
      MANAGEMENT: These predictors can assist managers and directors to identify
      targeted strategies for supervision and support of nursing staff to secure their
      well-being, and by that securing the quality of care provided to residents.

PMID- 19166524
TI  - Exploring the antecedents of organizational identification: the role of job
      dimensions, individual characteristics and job involvement.
AB  - AIM: This study aims to identify the antecedents of organizational identification
      such as job involvement and job dimensions in a health care setting. BACKGROUND:
      Organizational identification is an important work attitude that affects nurses'
      performance and job satisfaction. Hence, exploring antecedents of organizational
      identification in a health care setting is vital in understanding the role of
      organizational identification in nurse- and patient-related outcomes. METHOD: A
      research model, which incorporates job design, individual characteristics, job
      involvement and organizational identification, was developed and tested. The
      research was conducted via a survey in a hospital setting in Turkey (n = 148).
      RESULTS: The results revealed that job involvement, which is the degree of
      importance of one's job to one's self-image, is related to organizational
      identification. Among job dimensions, task identity and autonomy explained a
      significant proportion of variance in job involvement. CONCLUSION: Although job
      dimensions are not directly related to organizational identification, they have
      effects on job involvement, which is also an important construct. IMPLICATIONS
      FOR NURSING MANAGEMENT: The results suggest that nurses' jobs should be designed
      with higher levels of task autonomy and task identity to increase their job
      involvement and in turn their organizational identification.

PMID- 19166525
TI  - Barriers and facilitators to the achievement of community-focused public health
      nursing practice: a UK perspective.
AB  - AIM: To explore the extent to which Community Health Nurses (CHN) engage in
      community-focused public health practice and the facilitators and barriers to
      such practice. BACKGROUND: The government promotes the role of nurses in public
      health. However, there is confusion as to what constitutes public health; a lack
      of support to move from individual and family-focused practice to community
      focused practice; and, inconsistency of the use of titles. METHOD: A 15% quota
      sample (n = 409), drawn from a population of 2668 CHNs, participated in a
      quantitative survey. RESULTS: Response rate was 67% (n = 275). Over half of CHN
      time was spent with individuals and families, community level activity accounting
      for only 18%. Only 9% of respondents had completed a community needs assessment.
      Education was key to the promotion of community-focused practice with collection
      of individual activity data a major barrier. CONCLUSIONS: There is a gap between
      the rhetoric and reality of community public health nursing. IMPLICATIONS FOR
      NURSING MANAGEMENT: Development of a shared vision of public health nursing and
      commissioning of education to meet public health priorities is essential.
      Furthermore, strengthening public health nurse leadership to foster innovative
      practice and methods of measuring public health nursing outcomes is required.

PMID- 19166526
TI  - Validation of a tool to measure neonatal nursing workload.
AB  - AIMS: To test the validity and reliability of the Winnipeg Assessment of Neonatal
      Nursing Needs Tool (WANNNT). BACKGROUND: Workforce planning is increasingly
      challenging. Existing tools can be inadequate. METHODS: Nurses provided estimates
      of patient care time. Charge nurses assessed overall safety of care. Patient
      levels were compared between two independent assessors. Total nursing needs was
      compared between the WANNNT and an independent charge nurse. RESULTS: Mean time
      estimates for levels 1-5 were not significantly different from the WANNNT. Nurses
      estimated 50% less time than the tool assigned level 6. The tool was 95% reliable
      in assigning patient levels between two assessors. The mean difference between
      the total WANNNT assessment and the charge nurse was one nurse. CONCLUSIONS: The
      tool provided a reasonable and reliable estimation of the number of nurses
      required for a given collection of patients in order to provide the highest
      quality of care. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers
      incorporating this tool need to determine the additional drivers for nursing time
      that must be considered which may be unique to their unit or hospital. The WANNNT
      will be a valuable asset for making staffing decisions on a shift to shift and
      long-term basis.

PMID- 19166527
TI  - Nurses' intention to leave: critically analyse the theory of reasoned action and
      organizational commitment model.
AB  - AIM: To systematically analyse the Organizational Commitment model and Theory of
      Reasoned Action and determine concepts that can better explain nurses' intention
      to leave their job. BACKGROUND: The Organizational Commitment model and Theory of
      Reasoned Action have been proposed and applied to understand intention to leave
      and turnover behaviour, which are major contributors to nursing shortage.
      However, the appropriateness of applying these two models in nursing was not
      analysed. EVALUATION: Three main criteria of a useful model were used for the
      analysis: consistency in the use of concepts, testability and predictability. KEY
      ISSUES: Both theories use concepts consistently. Concepts in the Theory of
      Reasoned Action are defined broadly whereas they are operationally defined in the
      Organizational Commitment model. Predictability of the Theory of Reasoned Action
      is questionable whereas the Organizational Commitment model can be applied to
      predict intention to leave. A model was proposed based on this analysis.
      CONCLUSIONS: Organizational commitment, intention to leave, work experiences, job
      characteristics and personal characteristics can be concepts for predicting
      nurses' intention to leave. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers
      may consider nurses' personal characteristics and experiences to increase their
      organizational commitment and enhance their intention to stay. Empirical studies
      are needed to test and cross-validate the re-synthesized model for nurses'
      intention to leave their job.

PMID- 19166528
TI  - Contrasting burnout, turnover intention, control, value congruence and knowledge
      sharing between Baby Boomers and Generation X.
AB  - AIM(S): This paper examines the contrasting role of work values for nurses from
      two generations: Baby Boomers and Generation X. BACKGROUND: Differences among
      nurses regarding core values pertaining to their work has a potential to
      influence the quality of their work life. These differences may have implications
      for their vulnerability to job burnout. EVALUATION: The analysis is based upon
      questionnaire surveys of nurses representing Generation X (n = 255) and Baby
      Boomers (n = 193) that contrasted their responses on job burnout, areas of work
      life, knowledge transfer and intention to quit. KEY ISSUE(S): The analysis
      identified a greater person/organization value mismatch for Generation X nurses
      than for Baby Boomer nurses. Their greater value mismatch was associated with a
      greater susceptibility to burnout and a stronger intention to quit for Generation
      X nurses. CONCLUSION(S): The article notes the influence of Baby Boomer nurses in
      the structure of work and the application of new knowledge in health care work
      settings. Implications for recruitment and retention are discussed with a focus
      on knowledge transfer activities associated with distinct learning styles.
      IMPLICATIONS FOR NURSING MANAGEMENT: Understanding value differences between
      generations will help nursing managers to develop more responsive work settings
      for nurses of all ages.

PMID- 19166529
TI  - Juggling multiple temporalities: the shift work story of mid-life nurses.
AB  - AIM: To explore the theme of multiple temporalities revealed through a
      phenomenological study of the experience of mid-life shift-working nurses.
      BACKGROUND: There are few data on the experience of mid-life women working
      rotating shift systems that change frequently. Concomitantly, the age profile of
      the current nursing workforce demands exploration of such issues. METHOD: This
      phenomenological study sought the perspectives of 13 shift-working mid-life
      women. RESULTS: Sociological discussion of the temporal nature of work describes
      temporality as the clock time associated with an individual as determined by the
      constraints of their life. Transcript analysis identified the numerous
      temporalities surrounding a shift-working mid-life woman and a sense of
      disjunction between the temporalities of individuals important to them which
      resulted in feelings of regret and guilt. The concept of juggling is introduced
      to illustrate the participants' need to 'keep everything going' for important
      individuals in their lives. CONCLUSION: The personal cost of effective juggling
      may be high for the jugglers themselves but also for health systems that provide
      the mid-life shift-working nurse with no alternative than a reduction in working
      hours. IMPLICATIONS FOR NURSING MANAGEMENT: The development of a personal 'time
      map' framed within the concept of multiple temporalities is suggested for use as
      a staff development tool to assist with staff retention by facilitating both
      group and individual discussions of rostering and the complexities of managing an
      intergenerational work force undertaking shift work.

PMID- 19166530
TI  - Nurses' job satisfaction in their early career: is it the same for all branches
      of nursing?
AB  - AIM: To develop an early career job satisfaction instrument that is valid and
      reliable across the four UK nursing branches. BACKGROUND: Contemporary
      instruments are required to measure nurse job satisfaction and to explore
      potential links with quality of care and retention. METHOD(S): Factor analysis
      was used to explore and test the stability of job satisfaction components across
      branches and over time. RESULTS: Seven components (client care, staffing,
      development, relationships, education, work-life interface, resources) of job
      satisfaction were identified common to the adult, child and mental health
      branches that explained over 70% of the variance. The factor structure remained
      reasonably stable across time within each branch. Some differences between
      branches emerged at 6 and 18 months. The instrument has similarities and
      differences with existing generic and nursing facet job satisfaction scales.
      CONCLUSION: Findings support a generic instrument that can be used to measure the
      job satisfaction of adult, child and mental health nurses in their early career.
      IMPLICATIONS FOR NURSING MANAGEMENT: The instrument could be used for appraisal,
      annual staff surveys, for understanding retention locally and nationally, as an
      early warning system to identify organizational problems and to measure the
      impact of policies over time.

PMID- 19166531
TI  - The connection between personnel resources with work loading and patient
      satisfaction on in-patient wards.
AB  - AIM: The aim of the study is to describe the connection between the burden of
      nurses' work experience and patient dissatisfaction using electronic indicators
      available in databases. BACKGROUND: The hospitals in this study have a lot of
      information stored in electronic databases, but the data is stored in different
      databases and there are no straight connections between them. METHODS: This study
      was retrospective. Inpatient rates, workload statistics, patient classification,
      patient satisfaction and financial statistics were collected on 39 hospital wards
      from electronic databases. The data were analysed statistically. RESULTS: The
      results showed that the higher care intensity index and number of gross treatment
      days are, the greater was the burden on nurses. The burden was smaller on those
      wards using a named nurse system. CONCLUSIONS: Nurses' workload varies according
      to the condition of patients and patient flow. There is a connection between high
      workload and patient dissatisfaction. Nurse Managers should easily be able to use
      significant indicators. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing management
      must have tools that are easy to use in every day workload measurement, burden
      adjustment and personnel planning in the long run. This article presents patient
      classification and the number of beds used including daily change percentage of
      wards as instruments for nursing management.

PMID- 19166533
TI  - Medical experts and the law: Safeguarding children, the public and the
      profession.
AB  - Paediatricians working in child protection are sometimes required to act as
      expert witnesses in legal proceedings. Given the significant influence of opinion
      evidence on the jury, it is imperative that they understand their
      responsibilities to the court in this medico-legal interface and recognise their
      boundaries of expertise. Recent cases in the United Kingdom and in Australia have
      thrown the spotlight on paediatricians working as forensic experts in legal
      proceedings which has led to much public scrutiny and intervention by medical
      disciplinary bodies placing practice sanctions on child protection
      paediatricians. These decisions have had a significant impact on the workforce,
      with fewer paediatricians and those in training now willing to work in the field
      because of fears of disciplinary sanctions being instigated by those adversely
      affected by unfavourable forensic opinions. This article includes a detailed
      summary of these cases including excerpts from legal judgments, which highlight
      critical issues for the expert witness, which have had a significant impact on
      individuals, the profession and impacted on public confidence in the profession.
      In Australia, it is timely that we reflect on these lessons learnt and look to
      development of educational standards and forensic credentialing to enable
      continuity of a skilled paediatric workforce in child protection.

PMID- 19166534
TI  - Pulmonary haemorrhage in a 13-year-old girl: an unusual presentation of systemic
      lupus erythematosus.

PMID- 19166535
TI  - Anaphylaxis to paracetamol.

PMID- 19166536
TI  - An unusual cause of bilious vomiting in a neonate.

PMID- 19166537
TI  - Successful treatment of two cases of localised involutional lipoatrophy with
      intralesional normal saline.

PMID- 19166538
TI  - An unusual presentation of anaemia: a report of three cases.

PMID- 19166539
TI  - Re: AP-ROP in an infant with minimal oxygen exposure.

PMID- 19166540
TI  - Thoughts on the economy, academic dentistry, and the specialty of prosthodontics.

PMID- 19166541
TI  - Re: To boldly go where no man (prosthodontist) has gone before.

PMID- 19166542
TI  - Oral cancer: a prosthodontic diagnosis.
AB  - The prosthodontic literature is replete with articles addressing the
      reconstruction, psychological adaptation, prosthesis success, quality of life,
      need for careful follow-up, and many other issues related to the patient who has
      undergone surgery, radiation, and/or chemotherapy for oral malignant neoplasms.
      However, in the prosthodontic professional literature, there is a paucity of
      information related to the early diagnosis and referral of lesions that may
      represent premalignant or malignant neoplasia. This article will describe the
      rationale, epidemiology, and appearance of oral premalignant and malignant
      mucosal lesions as well as the state-of-the-art diagnostic tools currently
      available to prosthodontists to ensure that their patients are diagnosed at the
      earliest possible time.

PMID- 19166543
TI  - Human calmodulin-like protein (CLP) expression in oral squamous mucosa and in
      malignant transformation.
AB  - PURPOSE: The purpose of this study was to test whether calmodulin-like protein
      (CLP) is expressed in normal human oral mucosal cells and if downregulation of
      CLP occurs in malignant transformation. MATERIALS AND METHODS: Oral mucosal
      tissue was taken from three individuals in a double-blind manner. The samples
      were cut, measured, and homogenized. Total RNA was extracted and reverse
      transcribed. Each cDNA sample was subjected to polymerase chain reaction (PCR).
      PCR fragments were purified, cloned, and sequenced to verify the presence of CLP.
      Three oral mucosal tissue samples with biopsy-confirmed squamous cell carcinoma
      were obtained. These samples demonstrated regions of normal epithelial cells as
      well as invasive squamous cell carcinoma. One normal breast epithelial sample was
      also obtained for positive control. Sections were stained with an affinity
      purified CLP antibody and counterstained with a diluted hematoxylin. Two
      observers evaluated the specimens for expression of CLP. Staining patterns and
      intensity were noted in normal oral mucosa, comparing them to the normal breast
      epithelium sample. Staining patterns and intensity were then observed in squamous
      tumor cells, comparing them to the patterns of benign squamous mucosa. RESULTS:
      CLP coding sequences were positively identified from the normal oral mucosal
      tissue samples by reverse transcription and polymerase chain reaction (RT-PCR)
      with 100% identity to the published CLP sequence (accession #M58026). In the
      three oral mucosa tissue samples with known squamous cell carcinoma, expression
      of CLP was readily detected in areas of normal oral mucosa, while a notable
      downregulation of CLP expression occurred in areas of malignant transformation.
      The staining intensity was equivalent to the staining seen in the benign breast
      epithelium used as a control. In the areas of squamous cell carcinoma, a decrease
      in CLP immunoreactivity occurred. There was a sharp contrast in staining quality
      and clarity between benign and malignant tissue. In the majority of the carcinoma
      regions, a complete lack of immunoreactivity was noted. CONCLUSIONS: The RNA for
      human CLP is found in normal oral mucosa. CLP expression is seen in normal oral
      mucosa with a downregulation of CLP expression in malignant transformation.

PMID- 19166544
TI  - Fracture resistance of yttria-stabilized zirconia dental implant abutments.
AB  - PURPOSE: An in vitro study was performed to assess the effect of different
      degrees of clinical reduction of zirconia abutments on the failure load of
      clinical assemblies. MATERIALS AND METHODS: Zirconia abutments (Y-TZP Ceramic
      Abutment, Astra Tech) were prepared with 0, 0.5, or 1 mm of external axial
      reduction starting 1 mm above the height-of-contour. Abutments (n = 10) were
      attached to implant analogs (25 Ncm torque) embedded in a stainless steel
      cylinder using Field's metal. Fracture loads (N) were determined when assemblies
      were loaded at 60 degrees off-axis until failure (Instron, CHS = 0.1 mm/min).
      Groups were statistically compared using ANOVA (p < 0.05). RESULTS: Fracture
      loads for all assemblies displayed large variations within groups. There were no
      statistically significant differences (p > 0.05) among different abutment groups
      with a mean fracture load of 429 N (+/-140) for the control group, 576 N (+/-120)
      for 0.5-mm margins, and 547 (+/-139) for 1.0-mm margins. All fractures occurred
      at the interface where the abutment was connected to the analog. CONCLUSION: In
      this in vitro study of simulated ultimate assembly strength, the preparation of
      zirconia abutments did not significantly impair the fracture resistance of
      simulated implant assemblies. All implant abutments fractured at rates higher
      than the maximum incisal forces (90-370 N) estimated to occur in the anterior
      region of the mouth.

PMID- 19166545
TI  - The effects of primers and surface bonding characteristics on the adhesion of
      polyurethane to two commonly used silicone elastomers.
AB  - PURPOSE: When restoring facial defects, maxillofacial prosthodontists and
      anaplastologists are often limited by material deficiencies. Silicone elastomers
      bonded to a polyurethane liner best satisfy the functional and esthetic
      requirements necessary for facial prostheses; however, patients using silicone
      prostheses with polyurethane liners often experience varying degrees of debonding
      at the polyurethane-silicone interfaces. This may result in failure of such
      prostheses. The purpose of this investigation was to evaluate the effects of five
      primers on bonding between polyurethane and two commonly used silicone
      elastomers. MATERIAL AND METHODS: Six bonding regimens were used to join
      polyurethane and silicone materials. Each treatment group consisted of 12
      specimens. Bonding regimens included (1) a 40:60 mixture of MDX4-4210 and
      Silastic Medical Adhesive Type A, in conjunction with Dow Corning 1205 primer
      (Udagama's technique); (2) silicone A-2000 with Dow Corning 1205 primer; (3)
      silicone A-2000 with A-330-G primer; (4) silicone A-2000 with Mucopren primer;
      (5) silicone A-2000 with Sofreliner T primer; and (6) silicone A-2000 with
      Sofreliner MS primer. Following fabrication, specimens were attached to a
      universal testing machine and separated in tension at a crosshead speed of 25.4
      mm/min. One examiner performed the assessment of T-peel strength (N/mm), peak
      load (N), and peel distance (mm) for all specimens. Mean data were analyzed using
      one-way ANOVA followed by Fisher's protected significant difference multiple
      comparison of the means (alpha= 0.05). RESULTS: A statistically significant
      difference (p < 0.05) in T-peel strength was found among specimen groups. Post
      hoc analysis indicated that Sofreliner MS primer (1.32 +/- 0.13 N/mm) and
      Sofreliner T primer (1.25 +/- 0.11 N/mm) increased the bond strengths
      significantly compared to A-330-G primer (0.91 +/- 0.10 N/mm) and Udagama's
      technique (0.13 +/- 0.02 N/mm). Cohesive failure between silicone A-2000 and
      polyurethane liner was observed when Sofreliner MS primer and Sofreliner T were
      used. CONCLUSION: Within the limitations of this study, the use of Sofreliner MS
      primer and Sofreliner T primer produced significant increases in the bond
      strength of silicone elastomer to polyurethane liner material. Based on T-peel
      strength, peel distance, and peak load data, the combination of silicone A-2000
      and Sofreliner MS primer resulted in the greatest mean bond strength for silicone
      to-polyurethane applications.

PMID- 19166546
TI  - Influence of investment, disinfection, and storage on the microhardness of ocular
      resins.
AB  - PURPOSE: The longevity of an ocular prosthesis is directly related to the
      resistance to erosion of its material. The purpose of this study was to evaluate
      the effects of chemical disinfection and the method of investment on the
      microhardness of ocular prosthesis acrylic resin. MATERIALS AND METHODS: Thirty
      two test specimen investments were obtained in two silicones. A segment was cut
      in each test specimen, and each specimen was fixed in an acrylic disk. The
      specimens were then polished and submitted to the first microhardness test before
      immersion in distilled water and incubation for 2 months. During this 2-month
      period, the specimens were immersed in a water bath at 37 degrees C and were
      disinfected daily; half were disinfected with neutral soap and the other half
      were disinfected with 4% chlorhexidine gluconate. After the storage phase and
      disinfection, a second microhardness test was performed. The surface
      microhardness values for the acrylic resins were submitted to ANOVA, followed by
      the Tukey test. RESULTS: The disinfection and the period of storage did not
      statistically influence the surface microhardness of the acrylic resin,
      independent of the method of investment of the specimens (Zetalabor or Vipi Sil).
      The investment of specimens with Zetalabor silicone presented a greater surface
      hardness, independent of the type of disinfection and the period of storage.
      CONCLUSIONS: Based on these results, we suggest that the microhardness of the
      resin evaluated was not influenced by the method of disinfection or the time of
      storage used and was affected only by the investment material.

PMID- 19166547
TI  - Impact of interproximal groove placement and remaining coronal tooth structure on
      the fracture resistance of endodontically treated maxillary anterior teeth.
AB  - PURPOSE: This in vitro study investigated the effect of grooves, remaining tooth
      structure, and their combination on tooth fracture resistance of endodontically
      treated anterior teeth with cast dowel and cores. MATERIALS AND METHODS: Sixty
      extracted maxillary anterior teeth of similar dimensions were endodontically
      treated and then randomly divided into three groups of 20 teeth each. The teeth
      in the first group were cut horizontally at the widest part of their anatomical
      crowns. Three hundred and sixty degree 1 and 2 mm axial walls for ferrule effect
      were provided for the teeth in the second and the third groups, respectively.
      Cast dowel and cores were fabricated for all teeth. Each group was then
      subdivided in two groups: one with no grooves and another with mesial and distal
      grooves. Hence, six groups were created as follows: (1) teeth with no remaining
      coronal tooth structure and no grooves (group A-control); (2) teeth with no
      remaining coronal tooth structure, with mesial and distal grooves (group B); (3)
      teeth with 1 mm remaining coronal tooth structure, with no grooves (group C); (4)
      teeth with 1 mm remaining coronal tooth structure, with mesial and distal grooves
      (group D); (5) teeth with 2 mm remaining coronal tooth structure and no grooves
      (group E); and (6) teeth with 2 mm remaining coronal tooth structure, with mesial
      and distal grooves (group F). Complete cast crowns were then fabricated for all
      teeth. A universal testing machine applied controlled loads to the teeth at a
      crosshead speed of 2.54 mm/min at an angle of 130 degrees to the long axes of the
      teeth until failure occurred. The loads were applied 2 mm lower than the incisal
      edges of the specimens. Descriptive statistics, one-way ANOVA (alpha= 0.05) and
      Tukey's honestly significant difference (HSD) tests were used to determine the
      effect of failure loads among the tested groups (alpha= 0.05). RESULTS: The mean
      failure loads were (N): group A (control), 151.21 +/- 38.18; group B, 221.53 +/-
      107.03; group C, 295.35 +/- 81.92; group D, 270.20 +/- 76.01; group E, 491.70 +/-
      180.36; group F, 432.67 +/- 193.83. Group E presented the highest failure load
      and group A (control) the lowest. CONCLUSION: The inclusion of interproximal
      grooves on the cast dowel and cores of endodontically treated anterior teeth with
      1-2 mm of remaining coronal tooth structure does not significantly lower the
      failure threshold.

PMID- 19166548
TI  - Fracture resistance of endodontically treated teeth: three walls versus four
      walls of remaining coronal tooth structure.
AB  - PURPOSE: The purpose of this study was to evaluate the fracture resistance of
      endodontically treated teeth between those with four walls and those with three
      walls of remaining coronal tooth structure and the effect of the site of the
      missing coronal wall. MATERIALS AND METHODS: Thirty-two endodontically treated
      second mandibular premolars were decoronated, leaving 3 mm above the
      cementoenamel junction (CEJ). A 0.5-mm-wide chamfer was prepared 1 mm above the
      CEJ. The teeth were randomly divided into four groups. Group 1 had four walls of
      coronal tooth structure, whereas groups 2, 3, and 4 had only three walls, missing
      the buccal, lingual, and mesial wall, respectively. The cast dowel and cores and
      crowns (Ni-Cr alloy) were cemented with zinc phosphate cement. A compressive load
      was applied 45 degrees to the long axis, 2 mm below the buccal cusp, with an
      Instron machine until failure at a crosshead speed of 5 mm/min. Failure load (kg)
      and mode of failure were recorded. Data were analyzed with one-way ANOVA and
      Scheffe tests (p < 0.05). RESULTS: Group 1 had the highest fracture resistance
      (1190.3 +/- 110.5 kg), significantly different from the other groups (p < 0.05)
      (group 2: 578.5 +/- 197.4 kg; group 3: 786.6 +/- 132.8 kg; group 4: 785.4 +/-
      289.9 kg). There were no significant differences among the test groups. The mode
      of failure in group 1 was a horizontal root fracture, whereas that of the other
      groups was either vertical or oblique fracture. CONCLUSIONS: Teeth with four
      walls of remaining coronal dentine had significantly higher fracture resistance
      than teeth with only three walls. The site of the missing coronal wall did not
      affect the fracture resistance of endodontically treated teeth.

PMID- 19166549
TI  - An analysis of the effect of a vent hole on excess cement expressed at the crown
      abutment margin for cement-retained implant crowns.
AB  - PURPOSE: The labial margins of anterior implant-retained crowns are often
      positioned subgingivally for a superior esthetic appearance. One of the
      consequences of subgingival margins is the increased risk of leaving excess
      cement behind following cementation. This can lead to potential problems,
      including peri-implant inflammation, soft tissue swelling, soreness, bleeding or
      suppuration on probing, and bone loss. The purpose of this laboratory study was
      to investigate the effect of placement, location, and diameter of a vent hole on
      the amount of cement being expressed at the margin of an anterior implant
      abutment-retained crown. MATERIALS AND METHODS: Three implant crown copings were
      fabricated to fit on the same custom abutment. Three vent diameters (0.75, 1.25,
      and 1.65 mm) and three locations on the palatal surface of the coping (cervico
      palatally, mid-palatally, inciso-palatally) were chosen for vent hole placement.
      For each test, the coping was cemented onto the abutment under standardized
      conditions. A preweighed thin coating of cement was applied to the fit surface of
      the coping. The amount of cement expressed at the margin and vent hole was
      measured by weight and calculated as a proportion of the amount of cement placed
      in the coping before seating. The procedure was completed 15 times for each
      variable. The results were statistically analyzed using univariate ANOVA with
      post hoc Bonferroni-adjusted independent samples t-tests. RESULTS: The presence
      of a vent hole influenced the proportion of cement expressed at the coping margin
      (p < 0.05). The location of a vent hole influenced the proportion of cement
      expressed at the coping margin (p < 0.05), with the exception of the mid-palatal
      and inciso-palatal positioning where there was no significant difference (p=
      0.61) between groups. The diameter of the vent hole did not significantly
      influence the proportion of cement expressed at the coping margin (p= 0.096).
      CONCLUSIONS: When using anterior cement-retained implant crowns, the use of a
      0.75-mm mid-palatal or inciso-palatal vent hole to minimize the amount of cement
      expressed at the margin during cementation should be considered.

PMID- 19166550
TI  - Shade-matching abilities of dental laboratory technicians using a commercial
      light source.
AB  - PURPOSE: The purpose of this study was to evaluate dental laboratory technicians'
      abilities to match shades using a light-corrective device under conventional
      laboratory conditions. The variables measured were years experience, gender, and
      light source. MATERIALS AND METHODS: A 14-item shade-matching quiz (SMQ) was
      field-tested and deemed adequate. Information included age, gender, number of
      years experience, and Ishihara's Colour-Blindness Assessment. Forty-two dental
      technicians from five northeast Ohio laboratories were invited to participate.
      The SMQ was administered twice: under the lighting conditions in the individual
      laboratories (SMQ-Lab) and with a light-corrective source (SMQ-LC). For each
      item, the technicians were to select the matching Vita shade tab from five
      preselected shade tabs. SMQ scores equaled the number of correct matches.
      Statistical analysis included calculation of means, standard deviations,
      correlation coefficients, and independent and paired t-tests. Significance was
      set at p<or= 0.05. RESULTS: Twenty male and 20 female technicians participated.
      None were color-deficient. The SMQ scores were significantly higher with the
      light-corrective device than under laboratory lighting: 12.0 +/- 1.9 and 10.0 +/-
      2.0, respectively (p < 0.001). There were no significant correlations between
      years experience and SMQ scores, nor were there differences between scores by
      gender. In general, the Vita C shades were least likely to be matched.
      CONCLUSIONS: Within the limitations of this study, dental technicians' shade
      matching abilities were better with a light-corrective device than under the
      conventional laboratory lighting conditions. Gender and experience were not
      factors in matching shades. The Vita C shades were least likely to be matched.

PMID- 19166551
TI  - A transitional overlay partial denture for a young patient: a clinical report.
AB  - This clinical report describes a noninvasive approach for the treatment of a
      patient diagnosed with amelogenesis imperfecta (AI) and severe anterior open
      bite. The patient's functional and esthetic expectations were successfully met
      with a transitional overlay removable partial denture.

PMID- 19166555
TI  - Do children in rural areas still have different access to health care? Results
      from a statewide survey of Oregon's food stamp population.
AB  - PURPOSE: To determine if rural residence is independently associated with
      different access to health care services for children eligible for public health
      insurance. METHODS: We conducted a mail-return survey of 10,175 families randomly
      selected from Oregon's food stamp population (46% rural and 54% urban). With a
      response rate of 31%, we used a raking ratio estimation process to weight results
      back to the overall food stamp population. We examined associations between rural
      residence and access to health care (adjusting for child's age, child's
      race/ethnicity, household income, parental employment, and parental and child's
      insurance type). A second logistic regression model controlled for child's
      special health care needs. FINDINGS: Compared with urban children (reference =
      1.00), rural children were more likely to have unmet medical care needs (odds
      ratio [OR] 1.48, 95% confidence interval [CI] 1.07-2.04), problems getting dental
      care (OR 1.36, 95% CI 1.03-1.79), and at least one emergency department visit in
      the past year (OR 1.42, 95% CI 1.10-1.81). After adjusting for special health
      care needs (more prevalent among rural children), there was no rural-urban
      difference in unmet medical needs, but physician visits were more likely among
      rural children. There were no statistically significant differences in unmet
      prescription needs, delayed urgent care, or having a usual source of care.
      CONCLUSIONS: These findings suggest that access disparities between rural and
      urban low-income children persist, even after adjusting for health insurance.
      Coupled with continued expansions in children's health insurance coverage,
      targeted policy interventions are needed to ensure the availability of health
      care services for children in rural areas, especially those with special needs.

PMID- 19166556
TI  - Presence of a community health center and uninsured emergency department visit
      rates in rural counties.
AB  - CONTEXT: Community health centers (CHCs) provide essential access to a primary
      care medical home for the uninsured, especially in rural communities with no
      other primary care safety net. CHCs could potentially reduce uninsured emergency
      department (ED) visits in rural communities. PURPOSE: We compared uninsured ED
      visit rates between rural counties in Georgia that have a CHC clinic site and
      counties without a CHC presence. METHODS: We analyzed data from 100% of ED visits
      occurring in 117 rural (non-metropolitan statistical area [MSA]) counties in
      Georgia from 2003 to 2005. The counties were classified as having a CHC presence
      if a federally funded (Section 330) CHC had a primary care delivery site in that
      county throughout the study period. The main outcome measure was uninsured ED
      visit rates among the uninsured (all-cause ED visits and visits for ambulatory
      care sensitive conditions). Poisson regression models were used to examine the
      relationship between ED rates and the presence of a CHC. To ensure that the
      effects were unique to the uninsured population, we ran similar analyses on
      insured ED visits. FINDINGS: Counties without a CHC primary care clinic site had
      33% higher rates of uninsured all-cause ED visits per 10,000 uninsured population
      compared with non-CHC counties (rate ratio [RR] 1.33, 95% confidence interval
      [CI] 1.11-1.59). Higher ED visit rates remained significant (RR 1.21, 95% CI 1.02
      1.42) after adjustment for percentage of population below poverty level,
      percentage of black population, and number of hospitals. Uninsured ED visit rates
      were also higher for various categories of diagnoses, but remained statistically
      significant on multivariate analysis only for ambulatory care sensitive
      conditions (adjusted RR = 1.22, 95% CI 1.01-1.47). No such relationship was found
      for ED visit rates of insured patients (RR 1.06, 95% CI 0.92-1.22). CONCLUSIONS:
      The absence of a CHC is associated with a substantial excess in uninsured ED
      visits in rural counties, an excess not seen for ED visit rates among the
      insured.

PMID- 19166557
TI  - Sustaining the rural workforce: nursing perspectives on worklife challenges.
AB  - CONTEXT: Concerns have been raised about the sustainability of health care
      workforces in rural settings. According to the literature, rural nurses' work
      satisfaction varies with the resources and supports available to respond to
      specific challenges. Given the probable effects of stressors on retention, it is
      essential to understand the unique requirements of nurses in rural practice
      environments. PURPOSE: To investigate whether nurses receive the resources and
      supports necessary to meet the challenges of rural practice. METHODS: Semi
      structured interviews were conducted with 21 managers and 44 staff nurses in 19
      selected rural hospitals in Ontario, Canada. The interviews were taped and
      transcripts interpreted through a thematic analysis. Major worklife themes were
      identified and analyzed within a healthy work environment model based on the work
      of Kristensen. FINDINGS: Three interrelated dimensions of the model were relevant
      to workforce sustainability: the balance between demands and the resources of the
      person, the level of social support, and the degree of influence. The
      availability of resources and supports affected whether the nurses perceived
      challenges as stimulating or overwhelming. Deficits interfered with practice and
      the well-being of the nurses and patients. CONCLUSIONS: The nurses felt
      frustrated and powerless when they lacked resources, support, and influence to
      manage negative situations. Strategies to achieve workforce sustainability
      include resources to reduce stress in the workplace, education to meet the needs
      of new and experienced nurses, and offering of employment preferences to the
      workforce. Addressing resources, support, and influence of rural nurses is
      essential to alleviate workplace challenges and sustain the rural nursing
      workforce.

PMID- 19166558
TI  - Trends in the rehabilitation therapist workforce in underserved areas: 1980-2000.
AB  - CONTEXT: There is little information about how increases in the rehabilitation
      therapist workforce have been distributed over the nation. There is evidence that
      rural areas continue to face a shortage of trained rehabilitation providers.
      There has also been little attention to therapist distribution in non-rural
      settings where health professionals are in short supply. PURPOSE: To assess the
      change in the distribution of rehabilitation therapists in 1980, 1990, and 2000
      across counties with different levels of health professional shortages and the
      difference between metropolitan and non-metropolitan counties. METHODS: A trend
      analysis of cross-sectional data of employment of physical therapists,
      occupational therapists, and speech-language pathologists from 1980 to 2000 by
      county, relative to population, was done. The groups were stratified by shortage
      area, partial shortage area, and non-shortage counties and metropolitan and non
      metropolitan counties. FINDINGS: There is a maldistribution of rehabilitation
      therapists in the United States. Although the absolute differences have remained
      the same or, in most instances, have increased, the relative change was greatest
      in the shortage areas and non-metropolitan areas. If the trends in the relative
      changes continue, the absolute differences may begin to narrow. CONCLUSIONS: This
      study provides evidence that there are maldistributions of rehabilitation
      therapists in traditionally underserved areas. It is unclear if these
      maldistributions represent a shortage of rehabilitation therapists. Continued
      monitoring of the rehabilitation therapist workforce and the determination of the
      optimal supply should be undertaken in the future.

PMID- 19166559
TI  - Malpractice burden, rural location, and discontinuation of obstetric care: a
      study of obstetric providers in Michigan.
AB  - CONTEXT: It has long been a concern that professional liability problems
      disproportionately affect the delivery of obstetrical services to women living in
      rural areas. Michigan, a state with a large number of rural communities, is
      considered to be at risk for a medical liability crisis. PURPOSE: This study
      examined whether higher malpractice burden on obstetric providers was associated
      with an increased likelihood of discontinuing obstetric care and whether there
      were rural-urban differences in the relationship. METHODS: Data on 500
      obstetrician-gynecologists and family physicians who had provided obstetric care
      at some point in their career (either currently or previously) were obtained from
      a statewide survey in Michigan. Statistical tests and multivariate regression
      analyses were performed to examine the interrelationship among malpractice
      burden, rural location, and discontinuation of obstetric care. FINDINGS: After
      adjusting for other factors that might influence a physician's decision about
      whether to stop obstetric care, our results showed no significant impact of
      malpractice burden on physicians' likelihood to discontinue obstetric care. Rural
      urban location of the practice did not modify the nature of this relationship.
      However, family physicians in rural Michigan had a nearly 4-fold higher
      likelihood of withdrawing obstetric care when compared with urban family
      physicians. CONCLUSIONS: The higher likelihood of rural family physicians to
      discontinue obstetric care should be carefully weighed in future interventions to
      preserve obstetric care supply. More research is needed to better understand the
      practice environment of rural family physicians and the reasons for their
      withdrawal from obstetric care.

PMID- 19166560
TI  - Exploring the temperament and character traits of rural and urban doctors.
AB  - CONTEXT: Australia shares many dilemmas with North America regarding shortages of
      doctors in rural and remote locations. This preliminary study contributes to the
      establishment of a psychobiological profile for rural doctors by comparing
      temperament and character traits with an urban cohort. PURPOSE: The aim was to
      compare the individual levels and combinations of temperament (mildly heritable
      and stable) and character (developmental and modifiable) traits of rural and
      urban general practitioners (GPs). METHODS: Rural (n = 120) and urban (n = 94)
      GPs completed a demographic questionnaire and the TCI-R 140 to identify levels of
      the 7 basic dimensions of temperament and character. These are Novelty Seeking
      (NS), Harm Avoidance (HA), Reward Dependence (RD), Persistence (PS), Self
      Directedness (SD), Cooperativeness (CO), and Self-Transcendence (ST). FINDINGS:
      Preliminary results show rural GPs were higher in the temperament traits of NS
      and lower in HA compared with the urban sample. All female GPs were higher in RD
      and CO compared with all males, and all older GPs (over 55 years) were lower in
      RD compared with all younger GPs. CONCLUSIONS: This preliminary work may be the
      precursor to a new approach for the recruitment and retention of rural doctors
      through a greater awareness of personality traits conducive to the rural
      workforce. Further work may help inform appropriate policies to attract and
      retain this workforce and be a useful adjunct to the counseling of students
      interested in rural medicine by providing a better understanding of "what it
      takes" to be a rural doctor.

PMID- 19166561
TI  - Childhood conduct problems and other early risk factors in rural adult stimulant
      users.
AB  - CONTEXT: Understanding childhood risk factors associated with adult substance use
      and legal problems is important for treatment and prevention. PURPOSE: To examine
      the relationship of early substance use, conduct problems before age 15, and
      family history of substance abuse on adult outcomes in rural, stimulant users.
      METHODS: Adult cocaine and methamphetamine users (N = 544) in rural Arkansas and
      Kentucky were interviewed. Data were analyzed using both bivariate analyses and
      multiple logistic and log-linear regression models, with dependent variables
      being any substance abuse/dependence, stimulant abuse/dependence, total number of
      arrests since age 18 and days incarcerated since age 18. FINDINGS: One third
      reported 3 or more conduct disorder problems prior to age 15; half reported
      initiation of substances (excluding alcohol) before age 15; and 60% reported
      family history of substance problems. All 3 variables were associated with adult
      substance abuse/dependence but only the latter two were associated with stimulant
      abuse/dependence. CONCLUSIONS: This study highlights early risk factors for adult
      substance abuse/dependence among rural stimulant users.

PMID- 19166562
TI  - Rates of physical activity among Appalachian adolescents in Ohio.
AB  - PURPOSE: The purpose of this study was to describe the physical activity behavior
      of high school students living in the Appalachian region of Ohio. METHODS: A
      cross-sectional sample of 1,024 subjects from 11 schools in Appalachian Ohio was
      drawn. Previously validated instruments were used to measure physical activity
      behavior over 7 days. FINDINGS: Appalachian adolescents fell short of recommended
      levels of activity. They reported high rates of sedentary behavior by 9th grade.
      Appalachian adolescents may be acquiring sedentary behaviors earlier than
      adolescents living in other regions. Low rates of activity make this population
      particularly at risk for the health consequences associated with inactivity.

PMID- 19166563
TI  - Do older rural and urban veterans experience different rates of unplanned
      readmission to VA and non-VA hospitals?
AB  - CONTEXT: Unplanned readmission within 30 days of discharge is an indicator of
      hospital quality. PURPOSE: We wanted to determine whether older rural veterans
      who were enrolled in the VA had different rates of unplanned readmission to VA or
      non-VA hospitals than their urban counterparts. METHODS: We used the combined
      VA/Medicare dataset to examine 3,513,912 hospital admissions for older veterans
      that occurred in VA or non-VA hospitals between 1997 and 2004. We calculated 30
      day readmission rates and odds ratios for rural and urban veterans, and we
      performed a logistic regression analysis to determine whether living in a rural
      setting or initially using the VA for hospitalization were independent risk
      factors for unplanned 30-day readmission, after adjusting for age, sex, length of
      stay of the index admission, and morbidity. FINDINGS: Overall, rural veterans had
      slightly higher 30-day readmission rates than their urban counterparts (17.96% vs
      17.86%; OR 1.006, 95% CI: 1.0004, 1.013). For both rural- and urban-dwelling
      veterans, readmission after using a VA hospital was more common than after using
      a non-VA hospital (20.7% vs 16.8% for rural veterans, 21.2% vs 16.1% for urban
      veterans). After adjusting for other variables, readmission was more likely for
      rural veterans and following admission to a VA hospital. CONCLUSIONS: Our
      findings suggest that VA should consider using the unplanned readmission rate as
      a performance metric, using the non-VA experience of veterans as a performance
      benchmark, and helping rural veterans select higher performing non-VA hospitals.

PMID- 19166564
TI  - Factors associated with Iowa rural hospitals' decision to convert to critical
      access hospital status.
AB  - CONTEXT: The Balanced Budget Act (BBA) of 1997 allowed some rural hospitals
      meeting certain requirements to convert to Critical Access Hospitals (CAHs) and
      changed their Medicare reimbursement from prospective to cost-based. Some
      subsequent CAH-related laws reduced restrictions and increased payments, and the
      number of CAHs grew rapidly. PURPOSE: To examine factors related to hospitals'
      decisions to convert and time to CAH conversion. METHODS: Eighty-nine rural
      hospitals in Iowa were characterized and observed from 1998 to 2005. Cox
      proportional hazards models were used to identify the determinants of time to CAH
      conversion. FINDINGS: T-test and one-covariate Cox regression indicated that, in
      1998, Iowa rural hospitals with more staffed beds, discharges, and acute
      inpatient days, higher operating margin, lower skilled swing bed days relative to
      acute days, and located in relatively high density counties were more likely to
      convert later or not convert before 2006. Multiple Cox regression with baseline
      covariates indicated that lower number of discharges and average length of stay
      (ALOS) were significant after controlling all other covariates. CONCLUSION: Iowa
      rural hospitals' decisions regarding CAH conversion were influenced by hospital
      size, financial condition, skilled swing bed days relative to acute days, length
      of stay, proportion of Medicare acute days, and geographic factors. Although
      financial concerns are often cited in surveys as the main reason for conversion,
      lower number of discharges and ALOS are the most prominent factors affecting
      rural hospitals' decision on when to convert.

PMID- 19166565
TI  - Electronic patient registries improve diabetes care and clinical outcomes in
      rural community health centers.
AB  - CONTEXT: Diabetes care is challenging in rural areas. Research has shown that the
      utilization of electronic patient registries improves care; however, improvements
      generally have been described in combination with other ongoing interventions.
      The level of basic registry utilization sufficient for positive change is
      unknown. PURPOSE: The goal of the current study was to examine differential
      effects of basic registry utilization on diabetes care processes and clinical
      outcomes according to level of registry use in a rural setting. METHODS: Patients
      with diabetes (N = 661) from 6 Federally Qualified Health Centers in rural West
      Virginia were entered into an electronic patient registry. Data from pre- and
      post-registry were compared among 3 treatment and control groups that had
      different levels of registry utilization: low, medium, or high (for example,
      variations in the use of registry-generated progress notes examined at the point
      of-care and in the accuracy of registry-generated summary reports to track
      patients' care). Data included care processes (annual exams, screens to promote
      wellness, education, and self-management goal-setting) and clinical outcomes
      (HbA1c, LDL, HDL, cholesterol, triglycerides, blood pressure). FINDINGS: The
      registry assisted in significantly improving 12 of 13 care processes and 3 of 6
      clinical outcomes (HbA1c, LDL, cholesterol) for patients exposed to at least
      medium levels of registry utilization, but not for the controls. For example, the
      percent of patients who had received an annual eye exam at follow-up was 11%,
      34%, and 38% for the low, medium, and high utilization groups, respectively; only
      the latter groups improved. CONCLUSIONS: As an initial step to achieving control
      of diabetes, basic registry utilization may be sufficient to drive improvements
      in provider-patient care processes and in patient outcomes in rural clinics with
      few resources.

PMID- 19166566
TI  - Predisposing and enabling factors associated with mammography use among Hispanic
      and non-Hispanic white women living in a rural area.
AB  - CONTEXT: Women who do not receive regular mammograms are more likely than others
      to have breast cancer diagnosed at an advanced stage. PURPOSE: To examine
      predisposing and enabling factors associated with mammography use among Hispanic
      and non-Hispanic White women. METHODS: Baseline data were used from a larger
      study on cancer prevention in rural Washington state. In a sample of 20
      communities, 537 women formed the sample for this study. The main outcomes were
      ever having had a mammogram and having had a mammogram within the past 2 years.
      FINDINGS: Reporting ever having had a mammogram was inversely associated with
      lack of health insurance (OR = 0.37, 95% CI: 0.16-0.84), ages under 50 years (OR
      = 0.23, 95% CI: 0.12-0.45), high cost of exams (OR = 0.48, 95% CI: 0.27-0.87),
      and lack of mammography knowledge (OR = 0.16, 95% CI: 0.07-0.37), while
      increasing education levels were positively associated (OR = 1.72, 95% CI: 1.09
      2.70). Reporting mammography use within the past 2 years was inversely associated
      with ages under 50 years (OR = 0.49, 95% CI: 0.27-0.88) and over 70 years (OR =
      0.47, 95% CI: 0.24-0.94), lack of health insurance (OR = 0.23, 95% CI: 0.10
      0.50), and high cost of exams (OR = 0.55, 95% CI: 0.35-0.87). CONCLUSIONS:
      Continued resources and programs for cancer screening are needed to improve
      mammography participation among women without health insurance or low levels of
      education.

PMID- 19166567
TI  - Racial differences in HPV knowledge, HPV vaccine acceptability, and related
      beliefs among rural, southern women.
AB  - CONTEXT: Because cervical cancer mortality in the United States is twice as high
      among black women as white women and higher in rural areas, providing human
      papillomavirus (HPV) vaccine to rural black adolescents is a high priority.
      PURPOSE: To identify racial differences in knowledge and attitudes about HPV,
      cervical cancer, and the HPV vaccine that may influence uptake of the vaccine.
      METHODS: We interviewed women (91 black and 47 white) living in a rural area of
      the Southern United States in 2006. Analyses controlled for socioeconomic status,
      age, and recruitment location. FINDINGS: More white respondents had heard of HPV
      than had black respondents (57% vs 24%, P < .001), and whites had higher HPV
      knowledge (42% vs 29% correct responses, P < .05). Blacks were less likely than
      whites to think that cervical cancer would be a serious threat to their
      daughters' health (75% vs 96%, P < .001). More blacks than whites thought the
      ideal age to receive the vaccine was 17 years or older (63% vs 40%, P < .05).
      Blacks reported lower intentions to vaccinate their daughters than whites (M =
      4.14 vs 4.55, P < .05 in unadjusted analyses, but not statistically significant
      in adjusted analyses). CONCLUSIONS: Black and white respondents had different
      awareness, knowledge, and beliefs related to the HPV vaccine. Communication-based
      interventions to maximize uptake of the HPV vaccine in the rural, Southern United
      States may need different messages for black parents of adolescent girls.

PMID- 19166568
TI  - Health care utilization among migrant Latino farmworkers: the case of skin
      disease.
AB  - CONTEXT: Skin diseases are common occupational illnesses for migrant farmworkers.
      Farmworkers face many barriers in accessing health care resources. PURPOSE:
      Framed by the Health Behavior Model, the purpose of this study was to assess
      health care utilization for skin disease by migrant Latino farmworkers. METHODS:
      Three hundred and four migrant and seasonal Latino farmworkers in North Carolina
      were enrolled in a longitudinal study of skin disease and health care utilization
      over a single agricultural season. Self-reported and dermatologist-diagnosed skin
      condition data were collected at baseline and at up to 4 follow-up assessments.
      Medical visit rates were compared to national norms. FINDINGS: Self-reported skin
      problems and diagnosed skin disease were common among farmworkers. However, only
      34 health care visits were reported across the entire agricultural season, and
      none of the visits were for skin diseases. Nevertheless, self-treatment for skin
      conditions was common, including use of non-prescription preparations (63%),
      prescription products (9%), and home remedies (6%). General medical office visits
      were reported in 3.2% of the assessments, corresponding to 1.6 office visits per
      person year. CONCLUSIONS: The migrant farmworker population consists largely of
      young men who make little use of clinic services. Skin conditions are very common
      among these workers, but use of medical services for these conditions is not
      common. Instead, farmworkers rely primarily on self-treatment. Clinic-based
      studies of farmworker skin conditions will not account for most injury or disease
      in this population and have the potential for biased estimates.

PMID- 19166569
TI  - Body mass index and cancer screening in older American Indian and Alaska Native
      men.
AB  - CONTEXT: Regular screenings are important for reducing cancer morbidity and
      mortality. There are several barriers to receiving timely cancer screening,
      including overweight/obesity. No study has examined the relationship between
      overweight/obesity and cancer screening among American Indian/Alaska Natives
      (AI/ANs). PURPOSE: To describe the prevalence of fecal occult blood testing
      (FOBT) and prostate-specific antigen (PSA) testing among AI/AN men within the
      past year by age and rurality, and determine if body mass index (BMI) is
      associated with screening. METHODS: A national cross-sectional survey was
      administered face-to-face to 2,447 AI/AN men at least 55 years of age in 2004
      2005. Participants were asked when they last had FOBT and PSA testing. BMI was
      derived from self-reported height and weight, and rurality of residence was
      defined by rural-urban commuting area codes. We assessed the association of
      cancer screening and BMI with logistic regression models, adjusting for
      demographic and health factors. FINDINGS: Prevalence of up-to-date FOBT and PSA
      testing were 23% and 40%, respectively. Older men were more likely than younger
      men to have FOBT and PSA testing. BMI was not associated with receipt of FOBT or
      PSA testing. CONCLUSIONS: This is the first study to examine obesity and health
      care in AI/ANs. As in other populations, FOBT and PSA testing were suboptimal.
      Screening was not associated with BMI. Studies of AI/AN men are needed to
      understand the barriers to receiving timely screenings for prostate and
      colorectal cancer.

PMID- 19166570
TI  - An exploration of the relationship between depressive symptoms and cortisol
      rhythms in Colorado ranchers.
AB  - CONTEXT: Although the effects of stress on health have been studied in numerous
      urban-dwelling populations, fewer studies have addressed these effects in rural
      populations, such as farmers and ranchers. PURPOSE: The present study focuses on
      seasonal levels of depressed affect and perceived stress in Western Colorado
      ranchers, and how those phenomena related to their levels of cortisol. METHODS:
      Twenty-one (21) ranchers, who were permittees on the Colorado Grand Mesa,
      completed the study. Participants identified 2-week time periods during the year
      representing relative high, medium, and low stress. During each period,
      participants took saliva samples, rated stress levels, and completed a daily
      health diary. In addition, the Beck Depression Inventory (BDI-II), the perceived
      stress scale (PSS), and a life events scale (LES) were administered. RESULTS:
      Results showed a strong relationship between BDI-II and PSS scores (r = 0.748, P
      < .01). The decreased daytime cortisol decline supports the notion that the
      hypothalamic-pituitary-adrenal (HPA) axis negative feedback loop is disrupted in
      chronic stress and depression, thus resulting in chronically elevated cortisol
      levels. CONCLUSION: This study supports the relationship between stress,
      depression, and HPA dysregulation in ranchers.

PMID- 19166573
TI  - Three dimensions of oppositionality in youth.
AB  - BACKGROUND: Oppositional defiant disorder (ODD) in youth is a strong predictor of
      mental illness yet the wide range of associations with psychiatric disorders
      remains largely unexplained. The aim of this study was to investigate whether the
      identification of irritable, headstrong and hurtful dimensions within youth
      oppositionality would clarify the pattern of associations between oppositionality
      and a wide range of psychopathology in early and adult life. METHODS: Cross
      sectional data from national mental health surveys including 18,415 subjects aged
      5-16 in the United Kingdom. The main outcome measures were the associations
      between a priori hypothesised dimensions of oppositionality with psychiatric
      disorders and symptoms; parent and teacher-derived information were used in
      multivariate regression analysis. RESULTS: Our three a priori dimensions had very
      different associations with disorders and symptom scales. Irritability was the
      only predictor of emotional disorders (parent report: OR = 3.26 [CI 95% 2.79,
      3.80]; teacher report: OR = 2.78 [2.39, 3.22]); the hurtful dimension was
      particularly strongly associated with seeming cold-blooded or callous (parent
      report: beta = .32 [.27, .37]; teacher report: .33 [.30, .36]); and the
      headstrong dimension was most strongly associated with attention deficit
      hyperactivity disorder (ADHD; parent report: OR = 3.21 [2.43, 4.23]; teacher
      report : OR = 7.18 [5.25, 9.82]). All three dimensions were associated with
      conduct disorder, with the headstrong dimension being the main predictor of non
      aggressive symptoms (parent report: beta = .31 [.27, .34]; teacher report: .43
      [.40, .45]), and with the hurtful dimension being the main predictor of
      aggressive symptoms (parent report: beta = .35 [.32, .39]; teacher report: .40
      [.39, .42]). CONCLUSIONS: The three dimensions of oppositionality have
      distinctive external correlates, suggesting they may also be differential
      predictors of aetiology, prognosis and treatment responsiveness.

PMID- 19166574
TI  - Development of real time PCR for detection and quantitation of Dengue Viruses.
AB  - BACKGROUND: Dengue virus (DENV), a mosquito borne flavivirus is an important
      pathogen causing more than 50 million infections every year around the world.
      Dengue diagnosis depends on serology, which is not useful in the early phase of
      the disease and virus isolation, which is laborious and time consuming. There is
      need for a rapid, sensitive and high throughput method for detection of DENV in
      the early stages of the disease. Several real-time PCR assays have been described
      for dengue viruses, but there is scope for improvement. The new generation TaqMan
      Minor Groove Binding (MGB) probe approach was used to develop an improved real
      time RT-PCR (qRT-PCR) for DENV in this study. RESULTS: The 3'UTR of thirteen
      Indian strains of DENV was sequenced and aligned with 41 representative sequences
      from GenBank. A region conserved in all four serotypes was used to target primers
      and probes for the qRT-PCR. A single MGB probe and a single primer pair for all
      the four serotypes of DENV were designed. The sensitivity of the two step qRT-PCR
      assay was10 copies of RNA molecules per reaction. The specificity and sensitivity
      of the assay was 100% when tested with a panel of 39 known positive and negative
      samples. Viral RNA could be detected and quantitated in infected mouse brain,
      cell cultures, mosquitoes and clinical samples. Viral RNA could be detected in
      patients even after seroconversion till 10 days post onset of infection. There
      was no signal with Japanese Encephalitis (JE), West Nile (WN), Chikungunya (CHK)
      viruses or with Leptospira, Plasmodium vivax, Plasmodium falciparum and
      Rickettsia positive clinical samples. CONCLUSION: We have developed a highly
      sensitive and specific qRT-PCR for detection and quantitation of dengue viruses.
      The assay will be a useful tool for differential diagnosis of dengue fever in a
      situation where a number of other clinically indistinguishable infectious
      diseases like malaria, Chikungunya, rickettsia and leptospira occur. The ability
      of the assay to detect DENV-2 in inoculated mosquitoes makes it a potential tool
      for detecting DENV in field-caught mosquitoes.

PMID- 19166575
TI  - Abdominal angina in occlusive mesenteric vascular disease: a case report.
AB  - INTRODUCTION: Abdominal angina is a descriptive term for abdominal pain that can
      occur postprandially in patients with occlusive mesenteric vascular disease due
      to insufficient increase in blood flow. CASE PRESENTATION: In this case a 60-year
      old Caucasian woman with a 2 year history of abdominal angina presented to
      hospital for elective mesenteric revascularization surgery. Postoperative
      recovery was complicated by graft occlusion resulting in hepatic ischemia as well
      as splenic and small bowel infarction. CONCLUSION: This case highlights the
      importance of keeping this differential diagnosis in mind when dealing with
      patients who have a long history of abdominal pain and discusses some of the
      complications that may occur after surgical treatment.

PMID- 19166576
TI  - Linking social cognition with social interaction: Non-verbal expressivity, social
      competence and "mentalising" in patients with schizophrenia spectrum disorders.
AB  - BACKGROUND: Research has shown that patients with schizophrenia spectrum
      disorders (SSD) can be distinguished from controls on the basis of their non
      verbal expression. For example, patients with SSD use facial expressions less
      than normals to invite and sustain social interaction. Here, we sought to examine
      whether non-verbal expressivity in patients corresponds with their impoverished
      social competence and neurocognition. METHOD: Fifty patients with SSD were
      videotaped during interviews. Non-verbal expressivity was evaluated using the
      Ethological Coding System for Interviews (ECSI). Social competence was measured
      using the Social Behaviour Scale and psychopathology was rated using the Positive
      and Negative Symptom Scale. Neurocognitive variables included measures of IQ,
      executive functioning, and two mentalising tasks, which tapped into the ability
      to appreciate mental states of story characters. RESULTS: Non-verbal expressivity
      was reduced in patients relative to controls. Lack of "prosocial" nonverbal
      signals was associated with poor social competence and, partially, with impaired
      understanding of others' minds, but not with non-social cognition or medication.
      CONCLUSION: This is the first study to link deficits in non-verbal expressivity
      to levels of social skills and awareness of others' thoughts and intentions in
      patients with SSD.

PMID- 19166577
TI  - Transcriptomic comparison of Aspergillus niger growing on two different sugars
      reveals coordinated regulation of the secretory pathway.
AB  - BACKGROUND: The filamentous fungus, Aspergillus niger, responds to nutrient
      availability by modulating secretion of various substrate degrading hydrolases.
      This ability has made it an important organism in industrial production of
      secreted glycoproteins. The recent publication of the A. niger genome sequence
      and availability of microarrays allow high resolution studies of transcriptional
      regulation of basal cellular processes, like those of glycoprotein synthesis and
      secretion. It is known that the activities of certain secretory pathway enzymes
      involved N-glycosylation are elevated in response to carbon source induced
      secretion of the glycoprotein glucoamylase. We have investigated whether carbon
      source dependent enhancement of protein secretion can lead to upregulation of
      secretory pathway elements extending beyond those involved in N-glycosylation.
      RESULTS: This study compares the physiology and transcriptome of A. niger growing
      at the same specific growth rate (0.16 h(-1)) on xylose or maltose in carbon
      limited chemostat cultures. Transcription profiles were obtained using Affymetrix
      GeneChip analysis of six replicate cultures for each of the two growth-limiting
      carbon sources. The production rate of extracellular proteins per gram dry
      mycelium was about three times higher on maltose compared to xylose. The defined
      culture conditions resulted in high reproducibility, discriminating even low-fold
      differences in transcription, which is characteristic of genes encoding basal
      cellular functions. This included elements in the secretory pathway and central
      metabolic pathways. Increased protein secretion on maltose was accompanied by
      induced transcription of > 90 genes related to protein secretion. The upregulated
      genes encode key elements in protein translocation to the endoplasmic reticulum
      (ER), folding, N-glycosylation, quality control, and vesicle packaging and
      transport between ER and Golgi. The induction effect of maltose resembles the
      unfolded protein response (UPR), which results from ER-stress and has previously
      been defined by treatment with chemicals interfering with folding of
      glycoproteins or by expression of heterologous proteins. CONCLUSION: We show that
      upregulation of secretory pathway genes also occurs in conditions inducing
      secretion of endogenous glycoproteins - representing a more normal physiological
      state. Transcriptional regulation of protein synthesis and secretory pathway
      genes may thus reflect a general mechanism for modulation of secretion capacity
      in response to the conditional need for extracellular enzymes.

PMID- 19166579
TI  - Wegener's Granulomatosis presenting with an abscess in the parotid gland: a case
      report.
AB  - INTRODUCTION: Wegener's Granulomatosis is a vasculitis of uncertain aetiology.
      Affected patients usually present with disease of the respiratory and renal
      tracts. Classic symptoms and clinical findings, together with serology titres
      positive for anti-neutrophil cytolplasmic antibody against proteinase 3 confirm
      the diagnosis. Wegener's Granulomatosis can occasionally involve other organs,
      but solitary parotid gland disease is uncommon; patients generally also have
      systemic disease. CASE PRESENTATION: We report a case of Wegener's Granulomatosis
      in a 69-year-old Caucasian female presenting initially with an isolated parotid
      abscess and only subsequently developing nasal, paranasal sinus and respiratory
      symptoms. We describe the clinical course, diagnostic difficulties, imaging and
      histopathology of this case. CONCLUSION: Major salivary gland infection is not an
      uncommon ENT disorder, but the clinician should be wary of the patient who fails
      to respond appropriately to adequate therapy. In such cases a differential
      diagnosis of Wegener's Granulomatosis should be considered, as early recognition
      and treatment of this potentially fatal disease is paramount.

PMID- 19166578
TI  - Assembling proteomics data as a prerequisite for the analysis of large scale
      experiments.
AB  - BACKGROUND: Despite the complete determination of the genome sequence of a huge
      number of bacteria, their proteomes remain relatively poorly defined. Beside new
      methods to increase the number of identified proteins new database applications
      are necessary to store and present results of large- scale proteomics
      experiments. RESULTS: In the present study, a database concept has been developed
      to address these issues and to offer complete information via a web interface. In
      our concept, the Oracle based data repository system SQL-LIMS plays the central
      role in the proteomics workflow and was applied to the proteomes of Mycobacterium
      tuberculosis, Helicobacter pylori, Salmonella typhimurium and protein complexes
      such as 20S proteasome. Technical operations of our proteomics labs were used as
      the standard for SQL-LIMS template creation. By means of a Java based data
      parser, post-processed data of different approaches, such as LC/ESI-MS, MALDI-MS
      and 2-D gel electrophoresis (2-DE), were stored in SQL-LIMS. A minimum set of the
      proteomics data were transferred in our public 2D-PAGE database using a Java
      based interface (Data Transfer Tool) with the requirements of the PEDRo
      standardization. Furthermore, the stored proteomics data were extractable out of
      SQL-LIMS via XML. CONCLUSION: The Oracle based data repository system SQL-LIMS
      played the central role in the proteomics workflow concept. Technical operations
      of our proteomics labs were used as standards for SQL-LIMS templates. Using a
      Java based parser, post-processed data of different approaches such as LC/ESI-MS,
      MALDI-MS and 1-DE and 2-DE were stored in SQL-LIMS. Thus, unique data formats of
      different instruments were unified and stored in SQL-LIMS tables. Moreover, a
      unique submission identifier allowed fast access to all experimental data. This
      was the main advantage compared to multi software solutions, especially if
      personnel fluctuations are high. Moreover, large scale and high-throughput
      experiments must be managed in a comprehensive repository system such as SQL
      LIMS, to query results in a systematic manner. On the other hand, these database
      systems are expensive and require at least one full time administrator and
      specialized lab manager. Moreover, the high technical dynamics in proteomics may
      cause problems to adjust new data formats. To summarize, SQL-LIMS met the
      requirements of proteomics data handling especially in skilled processes such as
      gel-electrophoresis or mass spectrometry and fulfilled the PSI standardization
      criteria. The data transfer into a public domain via DTT facilitated validation
      of proteomics data. Additionally, evaluation of mass spectra by post-processing
      using MS-Screener improved the reliability of mass analysis and prevented storage
      of data junk.

PMID- 19166580
TI  - Meiotic and mitotic behaviour of a ring/deleted chromosome 22 in human embryos
      determined by preimplantation genetic diagnosis for a maternal carrier.
AB  - BACKGROUND: Ring chromosomes are normally associated with developmental anomalies
      and are rarely inherited. An exception to this rule is provided by deletion/ring
      cases. We were provided with a unique opportunity to investigate the meiotic
      segregation at oogenesis in a woman who is a carrier of a deleted/ring 22
      chromosome. The couple requested preimplantation genetic diagnosis (PGD)
      following the birth of a son with a mosaic karyotype.The couple underwent two
      cycles of PGD. Studies were performed on lymphocytes, single embryonic cells
      removed from 3 day-old embryos and un-transferred embryos. Analysis was carried
      out using fluorescence in situ hybridisation (FISH) with specific probe sets in
      two rounds of hybridization. RESULTS: In total, 12 embryos were biopsied, and
      follow up information was obtained for 10 embryos. No embryos were completely
      normal or balanced for chromosome 22 by day 5. There was only one embryo
      diagnosed as balanced of 12 biopsied but that accumulated postzygotic errors by
      day 5. Three oocytes apparently had a balanced chromosome 22 complement but all
      had the deleted and the ring 22 and not the intact chromosome 22. After
      fertilisation all the embryos accumulated postzygotic errors for chromosome 22.
      CONCLUSION: The study of the preimplantation embryos in this case provided a rare
      and significant chance to study and understand the phenomena associated with this
      unusual type of anomaly during meiosis and in the earliest stages of development.
      It is the first reported PGD attempt for a ring chromosome abnormality.

PMID- 19166581
TI  - An investigation of ribosomal protein L10 gene in autism spectrum disorders.
AB  - BACKGROUND: Autism spectrum disorders (ASD) are severe neurodevelopmental
      disorders with the male:female ratio of 4:1, implying the contribution of X
      chromosome genetic factors to the susceptibility of ASD. The ribosomal protein
      L10 (RPL10) gene, located on chromosome Xq28, codes for a key protein in
      assembling large ribosomal subunit and protein synthesis. Two non-synonymous
      mutations of RPL10, L206M and H213Q, were identified in four boys with ASD.
      Moreover, functional studies of mutant RPL10 in yeast exhibited aberrant
      ribosomal profiles. These results provided a novel aspect of disease mechanisms
      for autism--aberrant processes of ribosome biosynthesis and translation. To
      confirm these initial findings, we re-sequenced RPL10 exons and quantified mRNA
      transcript level of RPL10 in our samples. METHODS: 141 individuals with ASD were
      recruited in this study. All RPL10 exons and flanking junctions were sequenced.
      Furthermore, mRNA transcript level of RPL10 was quantified in B lymphoblastoid
      cell lines (BLCL) of 48 patients and 27 controls using the method of SYBR Green
      quantitative PCR. Two sets of primer pairs were used to quantify the mRNA
      expression level of RPL10: RPL10-A and RPL10-B. RESULTS: No non-synonymous
      mutations were detected in our cohort. Male controls showed similar transcript
      level of RPL10 compared with female controls (RPL10-A, U = 81, P = 0.7; RPL10-B,
      U = 61.5, P = 0.2). We did not observe any significant difference in RPL10
      transcript levels between cases and controls (RPL10-A, U = 531, P = 0.2; RPL10-B,
      U = 607.5, P = 0.7). CONCLUSION: Our results suggest that RPL10 has no major
      effect on the susceptibility to ASD.

PMID- 19166582
TI  - Trends in socioeconomic inequalities in cancer mortality in Barcelona: 1992-2003.
AB  - BACKGROUND: The objective of this study was to assess trends in cancer mortality
      by educational level in Barcelona from 1992 to 2003. METHODS: The study
      population comprised Barcelona inhabitants aged 20 years or older. Data on cancer
      deaths were supplied by the system of information on mortality. Educational level
      was obtained from the municipal census. Age-standardized rates by educational
      level were calculated. We also fitted Poisson regression models to estimate the
      relative index of inequality (RII) and the Slope Index of Inequalities (SII). All
      were calculated for each sex and period (1992-1994, 1995-1997, 1998-2000, and
      2001-2003). RESULTS: Cancer mortality was higher in men and women with lower
      educational level throughout the study period. Less-schooled men had higher
      mortality by stomach, mouth and pharynx, oesophagus, larynx and lung cancer. In
      women, there were educational inequalities for cervix uteri, liver and colon
      cancer. Inequalities of overall and specific types of cancer mortality remained
      stable in Barcelona; although a slight reduction was observed for some cancers.
      CONCLUSION: This study has identified those cancer types presenting the greatest
      inequalities between men and women in recent years and shown that in Barcelona
      there is a stable trend in inequalities in the burden of cancer.

PMID- 19166583
TI  - Inhibitory effects of rat bone marrow-derived dendritic cells on naive and
      alloantigen-specific CD4+ T cells: a comparison between dendritic cells generated
      with GM-CSF plus IL-4 and dendritic cells generated with GM-CSF plus IL-10.
AB  - BACKGROUND: Unlike mouse immature bone marrow (BM)-derived dendritic cells (DC),
      rat immature BMDC have not been thoroughly characterised in vitro for the
      mechanisms underlying their suppressive effect. To better characterise these
      mechanisms we therefore analysed the phenotypes and immune inhibitory properties
      of rat BMDC generated with GM-CSF plus IL-4 (= IL-4 DC) and with GM-CSF plus IL
      10 (= IL-10 DC). RESULTS: Both IL-4 DC and IL-10 DC exhibited lower surface
      expression of MHC class II and costimulatory molecules than mature splenic DC.
      They had a strong inhibitory effect on responsive T cells in vitro and despite
      their weak function as antigen-presenting cells they induced anergic T cells.
      However, only anergic T cells induced by IL-4 DC had a suppressive effect on
      responsive T cells. Induction of suppressive/tolerogenic T cells by IL-4 DC
      required direct contact between antigen-specific T cells and IL-4 DC. In
      addition, IL-4 DC and IL-10 DC prolonged allograft survival in an antigen
      specific manner. CONCLUSION: A unique phenotype of immature BMDC was isolated
      from the cultures. The mechanisms underlying the suppressive effect may be caused
      by their inability to deliver adequate costimulatory signals for T-cell
      activation. In addition, IL-4 DC but not IL-10 DC induce anergic T cells with
      suppressive function. This indicates that IL-4 DC and IL-10 DC may differ in the
      quality of their costimulation although no differences in the surface expression
      of costimulatory molecules were found.

PMID- 19166584
TI  - The first description of severe anemia associated with acute kidney injury and
      adult minimal change disease: a case report.
AB  - INTRODUCTION: Acute kidney injury in the setting of adult minimal change disease
      is associated with proteinuria, hypertension and hyperlipidemia but anemia is
      usually absent. Renal biopsies exhibit foot process effacement as well as tubular
      interstitial inflammation, acute tubular necrosis or intratubular obstruction. We
      recently managed a patient with unique clinical and pathological features of
      minimal change disease, who presented with severe anemia and acute kidney injury,
      an association not previously reported in the literature. CASE PRESENTATION: A 60
      year-old Indian-American woman with a history of hypertension and diabetes
      mellitus for 10 years presented with progressive oliguria over 2 days. Laboratory
      data revealed severe hyperkalemia, azotemia, heavy proteinuria and progressively
      worsening anemia. Urine eosinophils were not seen. Emergent hemodialysis,
      erythropoietin and blood transfusion were initiated. Serologic tests for
      hepatitis B, hepatitis C, anti-nuclear antibodies, anti-glomerular basement
      membrane antibodies and anti-neutrophil cytoplasmic antibodies were negative.
      Complement levels (C3, C4 and CH50) were normal. Renal biopsy unexpectedly
      displayed 100% foot process effacement. A 24-hour urine collection detected 6.38
      g of protein. Proteinuria and anemia resolved during six weeks of steroid
      therapy. Renal function recovered completely. No signs of relapse were observed
      at 8-month follow-up. CONCLUSION: Adult minimal change disease should be
      considered when a patient presents with proteinuria and severe acute kidney
      injury even when accompanied by severe anemia. This report adds to a growing body
      of literature suggesting that in addition to steroid therapy, prompt initiation
      of erythropoietin therapy may facilitate full recovery of renal function in acute
      kidney injury.

PMID- 19166585
TI  - Biopsychosocial approaches to a patient with vomiting of 10 years' duration--a
      case of temporal lobe epilepsy.
AB  - BACKGROUND: Vomiting is commonly encountered in clinical medicine. When organic
      gastrointestinal, metabolic, and brain diseases are ruled out, many cases are
      considered to be functional. We experienced an adult patient with epilepsy whose
      main symptom was vomiting. Biopsychosocial approaches were needed to control the
      symptoms. CASE PRESENTATION: A 26-year-old female with a 10-year history of
      persistent vomiting was found to have temporal lobe epilepsy (TLE). Throughout
      this time, during which the vomiting had become part of a vicious cycle, her
      epilepsy was poorly controlled by medication. Biopsychosocial approaches were
      employed successfully and the patient subsequently undertook training to become a
      home-helper, started a job, and was able to leave her parents' house and live
      independently. All of her symptoms resolved after she became self-sufficient.
      DISCUSSION: Vomiting without impaired consciousness is seldom considered to be a
      manifestation of epilepsy. Difficulty in recording an electroencephalogram (EEG)
      because of the presence of persistent vomiting delayed the diagnosis. The
      improvement of symptoms was thought to have been due to the patient's emotional
      stabilization and physical improvement, which may have stabilized the limbic
      system. CONCLUSION: When an illness persists for many years and conditioning and
      a vicious cycle occur secondarily, systematic biopsychosocial approaches are
      needed in addition to general treatment. Also, secondary symptoms make the
      diagnosis more difficult when efforts at treatment are ineffective.

PMID- 19166587
TI  - SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic
      leukemia-derived cell lines.
AB  - BACKGROUND: SET-NUP214 fusion resulting from a recurrent cryptic deletion,
      del(9)(q34.11q34.13) has recently been described in T-cell acute lymphoblastic
      leukemia (T-ALL) and in one case of acute myeloid leukemia (AML). The fusion
      protein appears to promote elevated expression of HOXA cluster genes in T-ALL and
      may contribute to the pathogenesis of the disease. We screened a panel of ALL and
      AML cell lines for SET-NUP214 expression to find model systems that might help to
      elucidate the cellular function of this fusion gene. RESULTS: Of 141 human
      leukemia/lymphoma cell lines tested, only the T-ALL cell line LOUCY and the AML
      cell line MEGAL expressed the SET(TAF-Ibeta)-NUP214 fusion gene transcript. RT
      PCR analysis specifically recognizing the alternative first exons of the two TAF
      I isoforms revealed that the cell lines also expressed TAF-Ialpha-NUP214 mRNA.
      Results of fluorescence in situ hybridization (FISH) and array-based copy number
      analysis were both consistent with del(9)(q34.11q34.13) as described.
      Quantitative genomic PCR also confirmed loss of genomic material between SET and
      NUP214 in both cell lines. Genomic sequencing localized the breakpoints of the
      SET gene to regions downstream of the stop codon and to NUP214 intron 17/18 in
      both LOUCY and MEGAL cells. Both cell lines expressed the 140 kDa SET-NUP214
      fusion protein. CONCLUSION: Cell lines LOUCY and MEGAL express the recently
      described SET-NUP214 fusion gene. Of special note is that the formation of the
      SET exon 7/NUP214 exon 18 gene transcript requires alternative splicing as the
      SET breakpoint is located downstream of the stop codon in exon 8. The cell lines
      are promising model systems for SET-NUP214 studies and should facilitate
      investigating cellular functions of the the SET-NUP214 protein.

PMID- 19166586
TI  - An analysis of synteny of Arachis with Lotus and Medicago sheds new light on the
      structure, stability and evolution of legume genomes.
AB  - BACKGROUND: Most agriculturally important legumes fall within two sub-clades of
      the Papilionoid legumes: the Phaseoloids and Galegoids, which diverged about 50
      Mya. The Phaseoloids are mostly tropical and include crops such as common bean
      and soybean. The Galegoids are mostly temperate and include clover, fava bean and
      the model legumes Lotus and Medicago (both with substantially sequenced genomes).
      In contrast, peanut (Arachis hypogaea) falls in the Dalbergioid clade which is
      more basal in its divergence within the Papilionoids. The aim of this work was to
      integrate the genetic map of Arachis with Lotus and Medicago and improve our
      understanding of the Arachis genome and legume genomes in general. To do this we
      placed on the Arachis map, comparative anchor markers defined using a previously
      described bioinformatics pipeline. Also we investigated the possible role of
      transposons in the patterns of synteny that were observed. RESULTS: The Arachis
      genetic map was substantially aligned with Lotus and Medicago with most synteny
      blocks presenting a single main affinity to each genome. This indicates that the
      last common whole genome duplication within the Papilionoid legumes predated the
      divergence of Arachis from the Galegoids and Phaseoloids sufficiently that the
      common ancestral genome was substantially diploidized. The Arachis and model
      legume genomes comparison made here, together with a previously published
      comparison of Lotus and Medicago allowed all possible Arachis-Lotus-Medicago
      species by species comparisons to be made and genome syntenies observed. Distinct
      conserved synteny blocks and non-conserved regions were present in all genome
      comparisons, implying that certain legume genomic regions are consistently more
      stable during evolution than others. We found that in Medicago and possibly also
      in Lotus, retrotransposons tend to be more frequent in the variable regions.
      Furthermore, while these variable regions generally have lower densities of
      single copy genes than the more conserved regions, some harbor high densities of
      the fast evolving disease resistance genes. CONCLUSION: We suggest that gene
      space in Papilionoids may be divided into two broadly defined components: more
      conserved regions which tend to have low retrotransposon densities and are
      relatively stable during evolution; and variable regions that tend to have high
      retrotransposon densities, and whose frequent restructuring may fuel the
      evolution of some gene families.

PMID- 19166588
TI  - An analysis of correlations among four outcome scales employed in clinical trials
      of patients with major depressive disorder.
AB  - BACKGROUND: The 17-item Hamilton Depression Rating Scale (HAM-D 17) remains the
      'gold standard' for measuring treatment outcomes in clinical trials of depressed
      patients. The Montgomery Asberg Depression Rating Scale (MADRS), Clinical Global
      Impressions-Severity (CGI-S) and -Improvement (CGI-I) scales are also widely
      used. OBJECTIVE: This analysis of data from 22 double-blind, placebo-controlled
      clinical studies of venlafaxine in adult patients with major depressive disorder
      was aimed at assessing correlations among these 4 scales. METHODS: Changes from
      baseline for MADRS, HAM-D 17 and CGI-S, and end point CGI-I scores and response
      (>or=50% decrease from baseline HAM-D 17 or MADRS, or CGI-S or CGI-I score <or=2)
      were analysed. Pearson correlation coefficients were calculated for all pairs of
      the four scales (HAM-D 17/MADRS, HAM-D 17/CGI-S, HAM-D 17/CGI-I, MADRS/CGI-S,
      MADRS/CGI-I, CGI-S/CGI-I) at different time points. Effect sizes were calculated
      using the Cohen d. RESULTS: Correlations were significant at all time points (p <
      0.0001), increased over the course of treatment, and were similar across
      treatment groups. Effect sizes ranged from 0.31 to 0.42; MADRS and CGI-I effect
      sizes were slightly greater compared with HAM-D 17 or CGI-S for continuous
      measures and response. CONCLUSION: Although MADRS and CGI-I were more sensitive
      to treatment effects, HAM-D 17, MADRS, CGI-S and CGI-I scores present a
      consistent picture of response to venlafaxine treatment.

PMID- 19166589
TI  - The multiplicity of malaria transmission: a review of entomological inoculation
      rate measurements and methods across sub-Saharan Africa.
AB  - Plasmodium falciparum malaria is a serious tropical disease that causes more than
      one million deaths each year, most of them in Africa. It is transmitted by a
      range of Anopheles mosquitoes and the risk of disease varies greatly across the
      continent. The "entomological inoculation rate" is the commonly-used measure of
      the intensity of malaria transmission, yet the methods used are currently not
      standardized, nor do they take the ecological, demographic, and socioeconomic
      differences across populations into account. To better understand the
      multiplicity of malaria transmission, this study examines the distribution of
      transmission intensity across sub-Saharan Africa, reviews the range of methods
      used, and explores ecological parameters in selected locations. It builds on an
      extensive geo-referenced database and uses geographical information systems to
      highlight transmission patterns, knowledge gaps, trends and changes in
      methodologies over time, and key differences between land use, population
      density, climate, and the main mosquito species. The aim is to improve the
      methods of measuring malaria transmission, to help develop the way forward so
      that we can better assess the impact of the large-scale intervention programmes,
      and rapid demographic and environmental change taking place across Africa.

PMID- 19166590
TI  - ArrayIDer: automated structural re-annotation pipeline for DNA microarrays.
AB  - BACKGROUND: Systems biology modeling from microarray data requires the most
      contemporary structural and functional array annotation. However, microarray
      annotations, especially for non-commercial, non-traditional biomedical model
      organisms, are often dated. In addition, most microarray analysis tools do not
      readily accept EST clone names, which are abundantly represented on arrays.
      Manual re-annotation of microarrays is impracticable and so we developed a
      computational re-annotation tool (ArrayIDer) to retrieve the most recent
      accession mapping files from public databases based on EST clone names or
      accessions and rapidly generate database accessions for entire microarrays.
      RESULTS: We utilized the Fred Hutchinson Cancer Research Centre 13K chicken cDNA
      array - a widely-used non-commercial chicken microarray - to demonstrate the
      principle that ArrayIDer could markedly improve annotation. We structurally re
      annotated 55% of the entire array. Moreover, we decreased non-chicken functional
      annotations by 2 fold. One beneficial consequence of our re-annotation was to
      identify 290 pseudogenes, of which 66 were previously incorrectly annotated.
      CONCLUSION: ArrayIDer allows rapid automated structural re-annotation of entire
      arrays and provides multiple accession types for use in subsequent functional
      analysis. This information is especially valuable for systems biology modeling in
      the non-traditional biomedical model organisms.

PMID- 19166591
TI  - Perfused human organs versus Mary Shelley's Frankenstein.
AB  - Novel drugs have to go through mandatory pre-clinical testing before they can be
      approved for use in clinical trials. In essence, it is a form of bench-to-bedside
      (N2B) translational medicine, but the wastage rate of target candidates is
      immensely high. Effects seen in vitro often do not translate to in vivo human
      settings. The search is on for better models closer to human physiology to be
      used in pre-clinical drug screening. The Ex Vivo Metrics system has been
      introduced where a human organ is harvested and revitalized in a controlled
      environment suitable for testing of both drug efficacy and potential toxicity.
      This commentary expresses the author's views regarding this technology of
      perfused human organs.

PMID- 19166593
TI  - An illustration of and programs estimating attributable fractions in large scale
      surveys considering multiple risk factors.
AB  - BACKGROUND: Attributable fractions (AF) assess the proportion of cases in a
      population attributable to certain risk factors but are infrequently reported and
      mostly calculated without considering potential confounders. While logistic
      regression for adjusted individual estimates of odds ratios (OR) is widely used,
      similar approaches for AFs are rarely applied. METHODS: Different methods for
      calculating adjusted AFs to risk factors of cardiovascular disease (CVD) were
      applied using data from the National Health and Nutrition Examination Survey
      (NHANES). We compared AFs from the unadjusted approach using Levin's formula,
      from Levin's formula using adjusted OR estimates, from logistic regression
      according to Bruzzi's approach, from logistic regression with sequential removal
      of risk factors ('sequential AF') and from logistic regression with all possible
      removal sequences and subsequent averaging ('average AF'). RESULTS: AFs following
      the unadjusted and adjusted (using adjusted ORs) Levin's approach yielded clearly
      higher estimates with a total sum of more than 100% compared to adjusted
      approaches with sums < 100%. Since AFs from logistic regression were related to
      the removal sequence of risk factors, all possible sequences were considered and
      estimates were averaged. These average AFs yielded plausible estimates of the
      population impact of considered risk factors on CVD with a total sum of 90%. The
      average AFs for total and HDL cholesterol levels were 17%, for hypertension 16%,
      for smoking 11%, and for diabetes 5%. CONCLUSION: Average AFs provide plausible
      estimates of population attributable risks and should therefore be reported at
      least to supplement unadjusted estimates. We provide functions/macros for
      commonly used statistical programs to encourage other researchers to calculate
      and report average AFs.

PMID- 19166592
TI  - Identification in milk of a serum amyloid A peptide chemoattractant for B
      lymphoblasts.
AB  - BACKGROUND: Normal mammary gland contains an extravascular population of B
      lymphoblasts, precursors of the immunoglobulin plasma cells that play a key role
      in the passive protection of neonates by secreting immunoglobulins to colostrum
      and milk. We investigated the presence of chemoattractants in the milk by
      analysing the chemoattractant activity of various fractions of this secretion.
      Milk chemoattractants are potentially involved in the recruitment of lymphocytes
      from the maternal bloodstream in lactating mammary glands. RESULTS: The dilution
      related lymphoid cell chemoattraction of whey was associated with a < 10 kDa
      ultrafiltrate. Active fractions were purified by reverse-phase high performance
      liquid chromatography. Two peptides of 2.7 kDa (DMREANYKNSDKYFHARGNYDAA) and 1
      kDa (RPPGLPDKY) were identified as fragments of the SAA protein family,
      tentatively identified as SAA2. Only the 2.7 kDa synthetic peptide displayed
      chemotactic activity, at two different optimal concentrations. At the lower
      concentration (3.7 nM), it attracted B-cell lymphoblasts, whereas at the higher
      (3.7 microM), it attracted B lymphocytes. Then, the SAA mRNA expression was
      analysed and we observed more SAA transcripts during lactation than gestation.
      CONCLUSION: These data are consistent with the SAA23-45 fragment being involved
      in preplasma B-cell recruitment to the mammary gland and resultant benefit to the
      neonate.

PMID- 19166594
TI  - Certified causes of death in patients with mesothelioma in South East England.
AB  - BACKGROUND: Mesothelioma is a highly fatal cancer that is caused by exposure to
      asbestos fibres. In many populations, the occurrence of mesothelioma is monitored
      with the use of mortality data from death certification. We examine certified
      causes of death of patients who have been diagnosed with mesothelioma, and assess
      the validity of death certification data as a proxy for mesothelioma incidence.
      METHODS: We extracted mesothelioma registrations in the South East of England
      area between 2000 and 2004 from the Thames Cancer Registry database. We retained
      for analysis 2200 patients who had died at the time of analysis, after having
      excluded seven dead cases where the causes of death were not known to the cancer
      registry. The 2200 deaths were classified hierarchically to identify (1)
      mesothelioma deaths, (2) deaths certified as lung cancer deaths or (3) deaths
      from unspecified cancer, and (4) deaths from other causes. RESULTS: 87% of the
      patients had mesothelioma mentioned on the death certificate. 6% had no mention
      of mesothelioma but included lung cancer as a cause of death. Another 6% had no
      mention of mesothelioma or lung cancer, but included an unspecified cancer as a
      cause of death. Lastly, 2% had other causes of death specified on the death
      certificate. CONCLUSION: This analysis suggests that official mortality data may
      underestimate the true occurrence of mesothelioma by around 10%.

PMID- 19166595
TI  - Aggregation of montmorillonite and organic matter in aqueous media containing
      artificial seawater.
AB  - BACKGROUND: The dispersion-aggregation behaviors of suspended colloids in rivers
      and estuaries are affected by the compositions of suspended materials (i.e., clay
      minerals vs. organic macromolecules) and salinity. Laboratory experiments were
      conducted to investigate the dispersion and aggregation mechanisms of suspended
      particles under simulated river and estuarine conditions. The average
      hydrodynamic diameters of suspended particles (representing degree of
      aggregation) and zeta potential (representing the electrokinetic properties of
      suspended colloids and aggregates) were determined for systems containing
      suspended montmorillonite, humic acid, and/or chitin at the circumneutral pH over
      a range of salinity (0 - 7.2 psu). RESULTS: The montmorillonite-only system
      increased the degree of aggregation with salinity increase, as would be expected
      for suspended colloids whose dispersion-aggregation behavior is largely
      controlled by the surface electrostatic properties and van der Waals forces. When
      montmorillonite is combined with humic acid or chitin, the aggregation of
      montmorillonite was effectively inhibited. The surface interaction energy model
      calculations reveal that the steric repulsion, rather than the increase in
      electronegativity, is the primary cause for the inhibition of aggregation by the
      addition of humic acid or chitin. CONCLUSION: These results help explain the
      range of dispersion-aggregation behaviors observed in natural river and estuarine
      systems. It is postulated that the composition of suspended particles,
      specifically the availability of steric polymers such as those contained in humic
      acid, determine whether the river suspension is rapidly aggregated and settled or
      remains dispersed in suspension when it encounters increasingly saline
      environments of estuaries and oceans.

PMID- 19166596
TI  - Circadian polymorphisms associated with affective disorders.
AB  - BACKGROUND: Clinical symptoms of affective disorders, their response to light
      treatment, and sensitivity to other circadian interventions indicate that the
      circadian system has a role in mood disorders. Possibly the mechanisms involve
      circadian seasonal and photoperiodic mechanisms. Since genetic susceptibilities
      contribute a strong component to affective disorders, we explored whether
      circadian gene polymorphisms were associated with affective disorders in four
      complementary studies. METHODS: Four groups of subjects were recruited from
      several sources: 1) bipolar proband-parent trios or sib-pair-parent nuclear
      families, 2) unrelated bipolar participants who had completed the BALM
      morningness-eveningness questionnaire, 3) sib pairs from the GenRed Project
      having at least one sib with early-onset recurrent unipolar depression, and 4) a
      sleep clinic patient group who frequently suffered from depression. Working
      mainly with the SNPlex assay system, from 2 to 198 polymorphisms in genes related
      to circadian function were genotyped in the participant groups. Associations with
      affective disorders were examined with TDT statistics for within-family
      comparisons. Quantitative trait associations were examined within the unrelated
      samples. RESULTS: In NR1D1, rs2314339 was associated with bipolar disorder (P =
      0.0005). Among the unrelated bipolar participants, 3 SNPs in PER3 and CSNK1E were
      associated with the BALM score. A PPARGC1B coding SNP, rs7732671, was associated
      with affective disorder with nominal significance in bipolar family groups and
      independently in unipolar sib pairs. In TEF, rs738499 was associated with
      unipolar depression; in a replication study, rs738499 was also associated with
      the QIDS-SR depression scale in the sleep clinic patient sample. CONCLUSION:
      Along with anti-manic effects of lithium and the antidepressant effects of bright
      light, these findings suggest that perturbations of the circadian gene network at
      several levels may influence mood disorders, perhaps ultimately through
      regulation of MAOA and its modulation of dopamine transmission. Twenty-three
      associations of circadian polymorphisms with affective symptoms met nominal
      significance criteria (P < 0.05), whereas 15 would be expected by chance,
      indicating that many represented false discoveries (Type II errors). Some
      evidence of replication has been gathered, but more studies are needed to
      ascertain if circadian gene polymorphisms contribute to susceptibility to
      affective disorders.

PMID- 19166597
TI  - Acute kidney injury in a patient with nontuberculous mycobacterial infections: a
      case report.
AB  - Nontuberculous mycobacterial infections are an increasingly recognized cause of
      chronic lung disease in both immunocompromised and immunocompetent patients. Pre
      existing lung disease, alcohol abuse, diabetes mellitus, malignancy, and smoking
      have been identified as important risk factors in nontuberculous mycobacterial
      infections, with only few cases of Nontuberculous mycobacterial infection in
      renal failure patients, mostly on peritoneal dialysis. However, acute kidney
      injury associated with atypical mycobacterial infection is a very rare clinical
      event. To our knowledge, the present patient is the first case of acute kidney
      injury in a patient with documented nontuberculous mycobacterial infection. Our
      case is also a first report of Mycobacteria avium complex and Mycobacteria
      gordonae isolated simultaneously from individual patient with nontuberculous
      mycobacterial disease.

PMID- 19166598
TI  - Hydatid cyst disease of the lung as an unusual cause of massive hemoptysis: a
      case report.
AB  - INTRODUCTION: Echinococcosis and/or hydatidosis is one of the most important
      zoonotic diseases in the world. In Turkey, echinococcosis is an endemic disease,
      however, hydatid disease of the lung is uncommon and usually caused by
      Echinococcus granulosus. CASE PRESENTATION: In this report we describe a 17-year
      old male patient who presented with massive hemoptysis due to hydatid disease of
      the lung. CONCLUSION: Although it is one of the less common causes of massive
      hemoptysis, hydatid disease of the lung requires greater attention in countries,
      such as Turkey, in which hydatid cyst disease is common.

PMID- 19166599
TI  - A patient with superior semicircular canal dehiscence presenting with Tullio's
      phenomenon: a case report.
AB  - INTRODUCTION: Superior semicircular canal dehiscence represents a manageable
      cause of sound and pressure induced vertigo. This case highlights its
      presentation and investigation, including a review of the literature, and the
      authors' surgical technique used in its successful treatment. CASE PRESENTATION:
      A 45-year-old Caucasian man presented with vertigo induced by sound or pressure.
      Subsequent investigation revealed dehiscence of the superior semicircular canal
      and the patient underwent a surgical repair. CONCLUSION: Surgery to repair or
      resurface the dehiscence represents an effective treatment modality, offering a
      resolution of symptoms with no detrimental effect on hearing or long-term
      sequelae. A five-layer composite repair consisting of temporalis fascia - bone
      pate - conchal cartilage - bone pate - temporalis fascia has been found to be
      safe and effective.

PMID- 19166600
TI  - Minimally invasive treatment of patients with bronchobiliary fistula: a case
      series.
AB  - INTRODUCTION: Bronchobiliary fistula is an uncommon complication secondary to
      hepatobiliary surgery. Bilioptysis is a pathognomic finding for bronchobiliary
      fistulas. Diagnosis may be easily established in the light of clinical history,
      which can be aided by imaging studies to pinpoint the exact location. Some
      diagnostic procedures such as endoscopic retrograde cholangiopancreatectomy are
      also useful for treatment. CASE PRESENTATION: We present three Turkish patients
      with bronchobiliary fistula secondary to previous hepatic surgery due to hydatid
      cyst in two, a 19-year-old and a 47-year-old man, and iatrogenic trauma of the
      common bile duct by endoscopy in a 35-year-old man. All of the patients were
      successfully treated by minimally invasive methods including percutaneous
      drainage and endoscopic retrograde cholangiopancreatography. CONCLUSION: We
      suggest that bronchobiliary fistula could be managed through conservative
      treatment methods which do not require in-hospital follow-up, particularly in
      uncomplicated cases. Otherwise, surgical management can be unavoidable.

PMID- 19166601
TI  - Cognitive interviewing methodology in the development of a pediatric item bank: a
      patient reported outcomes measurement information system (PROMIS) study.
AB  - BACKGROUND: The evaluation of patient-reported outcomes (PROs) in health care has
      seen greater use in recent years, and methods to improve the reliability and
      validity of PRO instruments are advancing. This paper discusses the cognitive
      interviewing procedures employed by the Patient Reported Outcomes Measurement
      Information System (PROMIS) pediatrics group for the purpose of developing a
      dynamic, electronic item bank for field testing with children and adolescents
      using novel computer technology. The primary objective of this study was to
      conduct cognitive interviews with children and adolescents to gain feedback on
      items measuring physical functioning, emotional health, social health, fatigue,
      pain, and asthma-specific symptoms. METHODS: A total of 88 cognitive interviews
      were conducted with 77 children and adolescents across two sites on 318 items.
      From this initial item bank, 25 items were deleted and 35 were revised and
      underwent a second round of cognitive interviews. A total of 293 items were
      retained for field testing. RESULTS: Children as young as 8 years of age were
      able to comprehend the majority of items, response options, directions, recall
      period, and identify problems with language that was difficult for them to
      understand. Cognitive interviews indicated issues with item comprehension on
      several items which led to alternative wording for these items. CONCLUSION:
      Children ages 8-17 years were able to comprehend most item stems and response
      options in the present study. Field testing with the resulting items and response
      options is presently being conducted as part of the PROMIS Pediatric Item Bank
      development process.

PMID- 19166602
TI  - Myocardial infarction with normal coronary arteries: a case report and review of
      the literature.
AB  - INTRODUCTION: Although acute myocardial infarction is generally associated with
      obstructive coronary artery disease, myocardial infarction associated with normal
      coronary arteries is a well-known condition. The overall prevalence rate of
      myocardial infarction with normal coronary arteries is considered to be low,
      varying from 1% to12% depending on the definition of "normal" coronary arteries.
      CASE PRESENTATION: We describe here a case of a 49-year-old woman with a history
      of prior myocardial infarction who continued to be asymptomatic after a 10-year
      follow-up, in the absence of a high-risk profile for adverse outcomes. She was
      studied with multi-slice coronary computed tomography and whole-body angiography,
      which showed normal coronary and extra-coronary arteries. CONCLUSION: This case
      report raises two important issues. First, the possible role of multi-slice
      computed tomography/coronary angiography in the risk- and prognosis assessment of
      patients with known or suspected coronary artery disease. Second, the important
      role played by long-term pharmacological therapy in patients with prior
      myocardial infarction and normal coronary arteries.

PMID- 19166603
TI  - A multiway analysis for identifying high integrity bovine BACs.
AB  - BACKGROUND: In large genomics projects involving many different types of analyses
      of bacterial artificial chromosomes (BACs), such as fingerprinting, end
      sequencing (BES) and full BAC sequencing there are many opportunities for the
      identities of BACs to become confused. However, by comparing the results from the
      different analyses, inconsistencies can be identified and a set of high integrity
      BACs preferred for future research can be defined. RESULTS: The location of each
      bovine BAC in the BAC fingerprint-based genome map and in the genome assembly
      were compared based on the reported BESs, and for a smaller number of BACs the
      full sequence. BACs with consistent positions in all three datasets, or if the
      full sequence was not available, for both the fingerprint map and BES-based
      alignments, were deemed to be correctly positioned. BACs with consistent BES
      based and fingerprint-based locations, but with conflicting locations based on
      the fully sequenced BAC, appeared to have been misidentified during sequencing,
      and included a number of apparently swapped BACs. Inconsistencies between BES
      based and fingerprint map positions identified thirty one plates from the CHORI
      240 library that appear to have suffered substantial systematic problems during
      the end-sequencing of the BACs. No systematic problems were identified in the
      fingerprinting of the BACs. Analysis of BACs overlapping in the assembly
      identified a small overrepresentation of clones with substantial overlap in the
      library and a substantial enrichment of highly overlapping BACs on the same plate
      in the CHORI-240 library. More than half of these BACs appear to have been
      present as duplicates on the original BAC-library plates and thus should be
      avoided in subsequent projects. CONCLUSION: Our analysis shows that approximately
      95% of the bovine CHORI-240 library clones with both a BAC fingerprint and two
      BESs mapping to the genome in the expected orientations (approximately 27% of all
      BACs) have consistent locations in the BAC fingerprint map and the genome
      assembly. We have developed a broadly applicable methodology for checking the
      integrity of BAC-based datasets even where only incomplete and partially
      assembled genomic sequence is available.

PMID- 19166604
TI  - Phylogeny of the SNARE vesicle fusion machinery yields insights into the
      conservation of the secretory pathway in fungi.
AB  - BACKGROUND: In eukaryotic cells, directional transport between different
      compartments of the endomembrane system is mediated by vesicles that bud from a
      donor organelle and then fuse with an acceptor organelle. A family of integral
      membrane proteins, termed soluble N-ethylmaleimide-sensitive factor attachment
      receptor (SNARE) proteins, constitute the key machineries of these different
      membrane fusion events. Over the past 30 years, the yeast Saccharomyces
      cerevisiae has served as a powerful model organism for studying the organization
      of the secretory and endocytic pathways, and a few years ago, its entire set of
      SNAREs was compiled. RESULTS: Here, we make use of the increasing amount of
      genomic data to investigate the history of the SNARE family during fungi
      evolution. Moreover, since different SNARE family members are thought to
      demarcate different organelles and vesicles, this approach allowed us to compare
      the organization of the endomembrane systems of yeast and animal cells. Our data
      corroborate the notion that fungi generally encompass a relatively simple set of
      SNARE proteins, mostly comprising the SNAREs of the proto-eukaryotic cell.
      However, all fungi contain a novel soluble SNARE protein, Vam7, which carries an
      N-terminal PX-domain that acts as a phosphoinositide binding module. In addition,
      the points in fungal evolution, at which lineage-specific duplications and
      diversifications occurred, could be determined. For instance, the endosomal
      syntaxins Pep12 and Vam3 arose from a gene duplication that occurred within the
      Saccharomycotina clade. CONCLUSION: Although the SNARE repertoire of baker's
      yeast is highly conserved, our analysis reveals that it is more deviated than the
      ones of basal fungi. This highlights that the trafficking pathways of baker's
      yeast are not only different to those in animal cells but also are somewhat
      different to those of many other fungi.

PMID- 19166605
TI  - Movement variability in stroke patients and controls performing two upper limb
      functional tasks: a new assessment methodology.
AB  - BACKGROUND: In the evaluation of upper limb impairment post stroke there remains
      a gap between detailed kinematic analyses with expensive motion capturing systems
      and common clinical assessment tests. In particular, although many clinical tests
      evaluate the performance of functional tasks, metrics to characterise upper limb
      kinematics are generally not applicable to such tasks and very limited in scope.
      This paper reports on a novel, user-friendly methodology that allows for the
      assessment of both signal magnitude and timing variability in upper limb movement
      trajectories during functional task performance. In order to demonstrate the
      technique, we report on a study in which the variability in timing and signal
      magnitude of data collected during the performance of two functional tasks is
      compared between a group of subjects with stroke and a group of individually
      matched control subjects. METHODS: We employ dynamic time warping for curve
      registration to quantify two aspects of movement variability: 1) variability of
      the timing of the accelerometer signals' characteristics and 2) variability of
      the signals' magnitude. Six stroke patients and six matched controls performed
      several trials of a unilateral ('drinking') and a bilateral ('moving a plate')
      functional task on two different days, approximately 1 month apart. Group
      differences for the two variability metrics were investigated on both days.
      RESULTS: For 'drinking from a glass' significant group differences were obtained
      on both days for the timing variability of the acceleration signals'
      characteristics (p = 0.002 and p = 0.008 for test and retest, respectively); all
      stroke patients showed increased signal timing variability as compared to their
      corresponding control subject. 'Moving a plate' provided less distinct group
      differences. CONCLUSION: This initial application establishes that movement
      variability metrics, as determined by our methodology, appear different in stroke
      patients as compared to matched controls during unilateral task performance
      ('drinking'). Use of a user-friendly, inexpensive accelerometer makes this
      methodology feasible for routine clinical evaluations. We are encouraged to
      perform larger studies to further investigate the metrics' usefulness when
      quantifying levels of impairment.

PMID- 19166606
TI  - Dietary patterns and quality in West-African immigrants in Madrid.
AB  - BACKGROUND: Eating patterns of immigrants deserve to be better documented because
      they may reflect the extent of acculturation and associated health risks. The
      study assessed dietary patterns and quality in Bubi immigrants (from Equatorial
      Guinea) using cluster analysis and comparing different diet quality indexes.
      METHODS: A random sample of 83 Bubi men and 130 women living in Madrid were
      studied. A 99-item food frequency questionnaire was administered, body weights
      and heights were self-reported and socio-demographic and health information was
      collected during interviews. Usual intakes were collapsed into 19 food groups.
      Cluster analysis of standardized food intakes per 1000 kcalories was performed.
      Dietary quality was appraised using the Alternative Mediterranean Diet Score, the
      Alternative Healthy Eating Index and scores of micronutrient adequacy and
      prevention based on WHO/FAO recommendations. RESULTS: Two dietary patterns were
      identified. The 'Healthier' pattern, so confirmed by two dietary quality indexes,
      featured a higher consumption of fish, fruits, vegetables, legumes, dairy
      products and bread while the 'Western' pattern included more processed meat,
      animal fat, and sweetened foods and drinks. One third of the subjects were in the
      'Healthier' food cluster, with the same proportion of men and women. Age >or= 30
      and residence in Madrid >or= 11 years were independently associated with the
      healthier diet. Consumption of traditional foods was unrelated to dietary
      pattern, however. Overall, Bubi diets were somewhat protective because of high
      intakes of fruits and vegetables and monounsaturated fat (olive oil), but not
      with respect to sugar, cholesterol, omega-3 fatty acids and fibre. Less than two
      thirds of subjects had adequate intakes of iron, calcium and folate in both
      dietary phenotypes. Body mass index, physical exercise, and self-reported health
      and cardiovascular disease condition showed no significant association with the
      dietary pattern. CONCLUSION: Cluster analysis combined with dietary quality
      assessment facilitates the interpretation of dietary patterns, but choosing the
      appropriate quality indexes is a problem. A small number of such indexes should
      be standardized and validated for international use. In the group studied,
      younger subjects and more recent immigrants were more likely to have a 'Western'
      pattern and should be a priority target for nutrition communication.

PMID- 19166607
TI  - Expiratory automatic endotracheal tube compensation reduces dynamic
      hyperinflation in a physical lung model.
AB  - INTRODUCTION: The effect of expiratory endotracheal tube (ETT) resistance on
      dynamic lung inflation is unknown. We hypothesized that ETT resistance causes
      dynamic lung hyperinflation by impeding lung emptying. We further hypothesized
      that compensation for expiratory ETT resistance by automatic tube compensation
      (ATC) attenuates dynamic lung hyperinflation. METHODS: A ventilator equipped with
      the original ATC mode and operating in a pressure-targeted mode was connected to
      a physical lung model that consists of four equally sized glass bottles filled
      with copper wool. Inspiratory pressure, peak expiratory flow, trapped lung volume
      and intrinsic positive end-expiratory pressure (PEEP) were assessed at
      combinations of four inner ETT diameters (7.0, 7.5, 8.0 and 8.5 mm), four
      respiratory rates (15, 20, 25 and 30/minute), three inspiratory pressures (3.0,
      4.5 and 6.0 cmH2O) and four lung compliances (113, 86, 58 and 28 ml/cmH2O).
      Intrinsic PEEP was measured at the end of an expiratory hold manoeuvre. RESULTS:
      At a given test lung compliance, inspiratory pressure and ETT size, increasing
      respiratory rates from 15 to 30/minutes had the following effects: inspiratory
      tidal volume and peak expiratory flow were decreased by means of 25% (range 0% to
      51%) and 11% (8% to 12%), respectively; and trapped lung volume and intrinsic
      PEEP were increased by means of 25% (0% to 51%) and 26% (5% to 45%), respectively
      (all P < 0.025). At otherwise identical baseline conditions, introduction of
      expiratory ATC significantly attenuated (P < 0.025), by approximately 50%, the
      respiratory rate-dependent decreases in inspiratory tidal volume and the
      increases in trapped lung volume and intrinsic PEEP. CONCLUSIONS: In a lung model
      of pressure-targeted ventilation, expiratory ETT resistance caused dynamic lung
      hyperinflation during increases in respiratory rates, thereby reducing
      inspiratory tidal volume. Expiratory ATC attenuated these adverse effects.

PMID- 19166608
TI  - A systematic review of the evidence of the burden of bipolar disorder in Europe.
AB  - BACKGROUND: Bipolar disorder is recognized as a major mental health issue, and
      its economic impact has been examined in the United States. However, there exists
      a general scarcity of published studies and lack of standardized data on the
      burden of the illness across European countries. In this systematic literature
      review, we highlight the epidemiological, clinical, and economic outcomes of
      bipolar disorder in Europe. METHODS: A systematic review of publications from the
      last 10 years relating to the burden of bipolar disorder was conducted, including
      studies on epidemiology, patient-related issues, and costs. RESULTS: Data from
      the UK, Germany, and Italy indicated a prevalence of bipolar disorder of ~1%, and
      a misdiagnosis rate of 70% from Spain. In one study, up to 75% of patients had at
      least one DSM-IV comorbidity, commonly anxiety disorders and substance/alcohol
      abuse. Attempted suicide rates varied between 21%-54%. In the UK, the estimated
      rate of premature mortality of patients with bipolar I disorder was 18%. The
      chronicity of bipolar disorder exerted a profound and debilitating effect on the
      patient. In Germany, 70% of patients were underemployed, and 72% received
      disability payments. In Italy, 63%-67% of patients were unemployed. In the UK,
      the annual costs of unemployment and suicide were pound1510 million and pound179
      million, respectively, at 1999/2000 prices. The estimated UK national cost of
      bipolar disorder was pound4.59 billion, with hospitalization during acute
      episodes representing the largest component. CONCLUSION: Bipolar disorder is a
      major and underestimated health problem in Europe. A number of issues impact on
      the economic burden of the disease, such as comorbidities, suicide, early death,
      unemployment or underemployment. Direct costs of bipolar disorder are mainly
      associated with hospitalization during acute episodes. Indirect costs are a major
      contributor to the overall economic burden but are not always recognized in
      research studies.

PMID- 19166609
TI  - Chest pain and ST-segment elevation in a patient with polymyositis: a case
      report.
AB  - BACKGROUND: Cardiac involvement in patients with polymyositis is well-documented
      and includes myocarditis, coronary arteritis, pericarditis, valvular dysfunction
      and arrhythmias. CASE REPORT: There are only few reports of acute myocarditis in
      patients with polymyositis and, although it usually follows a chronic, mild
      course, it may occasionally become life-threatening. We describe the case of a 36
      year-old young woman suffering from polymyositis who presented with clinical
      signs and symptoms mimicking an ST Elevation Acute Coronary Syndrome. The
      atypical features of the pain, the young age of the woman, the lack of
      significant cardiovascular risk factors and the medical history of an autoimmune
      disease, led us to reconsider our initial diagnosis towards the presence of focal
      myocarditis. CONCLUSION: We describe our diagnostic approach and comment on our
      speculations and decisions about the treatment of such a life threatening event.

PMID- 19166610
TI  - Genome Projector: zoomable genome map with multiple views.
AB  - BACKGROUND: Molecular biology data exist on diverse scales, from the level of
      molecules to -omics. At the same time, the data at each scale can be categorised
      into multiple layers, such as the genome, transcriptome, proteome, metabolome,
      and biochemical pathways. Due to the highly multi-layer and multi-dimensional
      nature of biological information, software interfaces for database browsing
      should provide an intuitive interface that allows for rapid migration across
      different views and scales. The Zoomable User Interface (ZUI) and tabbed browsing
      have proven successful for this purpose in other areas, especially to navigate
      the vast information in the World Wide Web. RESULTS: This paper presents Genome
      Projector, a Web-based gateway for genomics information with a zoomable user
      interface using Google Maps API, equipped with four seamlessly accessible and
      searchable views: a circular genome map, a traditional genome map, a biochemical
      pathways map, and a DNA walk map. The Web application for 320 bacterial genomes
      is available at http://www.g-language.org/GenomeProjector/. All data and software
      including the source code, documentations, and development API are freely
      available under the GNU General Public License. Zoomable maps can be easily
      created from any image file using the development API, and an online data mapping
      service for Genome Projector is also available at our Web site. CONCLUSION:
      Genome Projector is an intuitive Web application for browsing genomics
      information, implemented with a zoomable user interface and tabbed browsing
      utilising Google Maps API and Asynchronous JavaScript and XML (AJAX) technology.

PMID- 19166611
TI  - Prevalence, evaluation and management of overactive bladder in primary care.
AB  - BACKGROUND: Patients with overactive bladder (OAB) are under-diagnosed in the
      primary care setting. Primary care physicians (PCP) approach to the patient and
      appropriate patient disclosure may contribute to under-diagnosis. METHODS: An
      outpatient primary care setting was used to determine the prevalence and
      characteristics of OAB. Patients who visited the family medicine outpatient
      clinic were invited to answer a self-administered questionnaire. It included
      questions on evidence of lower urinary tract symptoms (modified Overactive
      Bladder-Validated 8-question Screener [OAB-V8]), relevant medical and surgical
      history, and demographic data. Relationship between OAB and other independent
      variables were analyzed using chi-square and risk ratio (RR) analysis. RESULTS:
      Of 325 questionnaires distributed, 311 were returned completed. Patients ranged
      from 18 to 97 years, the majority women (74.0%) and African American (74.3%). OAB
      was present in 60.5% of men and 48.3% of women (p = 0.058). OAB was significantly
      associated with obesity (BMI > or = 30) in women (p = 0.018, RR = 1.72),
      specifically obese premenopausal women (age < 55 years) (p = 0.011, RR = 1.98).
      CONCLUSION: OAB prevalence is more than double and higher in men than previously
      reported. The relative risk for OAB is significantly greater in obese
      premenopausal women.

PMID- 19166612
TI  - Alteration of renal respiratory Complex-III during experimental type-1 diabetes.
AB  - BACKGROUND: Diabetes has become the single most common cause for end-stage renal
      disease in the United States. It has been established that mitochondrial damage
      occurs during diabetes; however, little is known about what initiates
      mitochondrial injury and oxidant production during the early stages of diabetes.
      Inactivation of mitochondrial respiratory complexes or alteration of their
      critical subunits can lead to generation of mitochondrial oxidants, mitochondrial
      damage, and organ injury. Thus, one goal of this study was to determine the
      status of mitochondrial respiratory complexes in the rat kidney during the early
      stages of diabetes (5-weeks post streptozotocin injection). METHODS:
      Mitochondrial complex activity assays, blue native gel electrophoresis (BN-PAGE),
      Complex III immunoprecipitation, and an ATP assay were performed to examine the
      effects of diabetes on the status of respiratory complexes and energy levels in
      renal mitochondria. Creatinine clearance and urine albumin excretion were
      measured to assess the status of renal function in our model. RESULTS:
      Interestingly, of all four respiratory complexes only cytochrome c reductase
      (Complex-III) activity was significantly decreased, whereas two Complex III
      subunits, Core 2 protein and Rieske protein, were up regulated in the diabetic
      renal mitochondria. The BN-PAGE data suggested that Complex III failed to
      assemble correctly, which could also explain the compensatory upregulation of
      specific Complex III subunits. In addition, the renal F0F1-ATPase activity and
      ATP levels were increased during diabetes. CONCLUSION: In summary, these findings
      show for the first time that early (and selective) inactivation of Complex-III
      may contribute to the mitochondrial oxidant production which occurs in the early
      stages of diabetes.

PMID- 19166613
TI  - Fatty acid composition of subcutaneous adipose tissue and gastric mucosa: is
      there a relation with gastric ulceration?
AB  - BACKGROUND: Both in vitro and epidemiological studies indicate that dietary
      polyunsaturated fatty acids may play a protective role against peptic ulcer in
      humans. Adipose tissue fatty acid composition is thought to reflect dietary fatty
      acid intake. The aim of the present study is to investigate adipose and gastric
      mucosa fatty acid levels in relation to gastric ulceration status. METHODS: Fifty
      two adult outpatients undergoing upper gastrointestinal tract endoscopy
      participated in the study. Adipose tissue samples were taken from the abdomen and
      buttock during the endoscopy procedure and samples from gastric tissue were taken
      from a subsample of 30 subjects. The presence of Helicobacter pylori was
      determined using the CLO test. Capillary gas chromatography was used for the
      extraction of 36 and 42 adipose tissue and gastric mucosa lipids respectively.
      RESULTS: The monounsaturated fatty acids (MUFAs) C18:1n-12c, C16:1n-5, C16:4n-1
      and the polyunsaturated fatty acids (PUFAs) C16:3n-4, C20:3n-3, C20:4n-6, C21:5n
      3 and C18:2n-9c,12t of the gastric mucosa were present in higher proportions in
      ulcer negative patients. These unsaturated fatty acids, however, each contributed
      less than 1% on average to total fatty acid content. In addition, higher average
      levels of eicosapentaenoic acid (EPA) C20:5n-3 and docosahexaenoic acid (DHA)
      C22:6n-3 were detected in abdominal and buttock samples in CLO negative controls,
      compared to CLO positive controls. Adipose tissue and gastric mucosa n-6 and
      trans fatty acid levels were positively linearly correlated (r = 0.37 and 0.41
      for n-6 and trans fatty acids respectively). CONCLUSION: Certain minor MUFAs and
      PUFAs of the gastric mucosa appear to be present in higher proportions in ulcer
      negative patients. Overall, the findings provide only weak evidence of an
      association between the gastric mucosal fatty acids and the presence of gastric
      ulceration. The higher average levels of EPA and DHA in abdominal and buttock
      adipose tissue in CLO negative controls could be an indicator that dietary FAs
      inhibit Helicobacter pylori growth. Larger studies are necessary to provide
      evidence of a biologically relevant effect.

PMID- 19166615
TI  - Adverse clinical sequelae after skin branding: a case series.
AB  - INTRODUCTION: Branding refers to a process whereby third degree burns are
      inflicted on the skin with a hot iron rod or metallic object. Branding employs
      the phenomenon of "counter irritation," and is widely used by faith healers in
      developing countries for therapeutic purposes. Some methods, which are very crude
      and inhuman, carry a large risk of complications. The purpose of this study is to
      present a series of complications and to familiarize clinicians with this
      dangerous method of treatment. CASE PRESENTATION: Four Pakistani patients, three
      male and one female, ranging from 25 to 60 years of age "branded" with a red hot
      iron rod for various medical reasons presented with severe medical complications
      to our tertiary care hospital. The mean duration between the procedure and
      presentation to the hospital was 6 days. At the time of admission, two patients
      had septic shock, one patient had cavernous sinus thrombosis and one patient had
      multiple splenic abscesses. All patients received standard care for wound
      management and systemic infections. Two patients eventually died during the
      course of treatment. CONCLUSION: Severe complications from branding are
      troublesome and the potential risks of this treatment outweigh its benefits.
      Globally, there is a great need for heightened awareness about the dangers of
      branding among patients and physicians, as this will have an important effect on
      patients who seek branding for various medical conditions.

PMID- 19166614
TI  - Brain-derived neurotrophic factor modulation of Kv1.3 channel is disregulated by
      adaptor proteins Grb10 and nShc.
AB  - BACKGROUND: Neurotrophins are important regulators of growth and regeneration,
      and acutely, they can modulate the activity of voltage-gated ion channels.
      Previously we have shown that acute brain-derived neurotrophic factor (BDNF)
      activation of neurotrophin receptor tyrosine kinase B (TrkB) suppresses the
      Shaker voltage-gated potassium channel (Kv1.3) via phosphorylation of multiple
      tyrosine residues in the N and C terminal aspects of the channel protein. It is
      not known how adaptor proteins, which lack catalytic activity, but interact with
      members of the neurotrophic signaling pathway, might scaffold with ion channels
      or modulate channel activity. RESULTS: We report the co-localization of two
      adaptor proteins, neuronal Src homology and collagen (nShc) and growth factor
      receptor-binding protein 10 (Grb10), with Kv1.3 channel as demonstrated through
      immunocytochemical approaches in the olfactory bulb (OB) neural lamina. To
      further explore the specificity and functional ramification of adaptor/channel co
      localization, we performed immunoprecipitation and Western analysis of channel,
      kinase, and adaptor transfected human embryonic kidney 293 cells (HEK 293). nShc
      formed a direct protein-protein interaction with Kv1.3 that was independent of
      BDNF-induced phosphorylation of Kv1.3, whereas Grb10 did not complex with Kv1.3
      in HEK 293 cells. Both adaptors, however, co-immunoprecipitated with Kv1.3 in
      native OB. Grb10 was interestingly able to decrease the total expression of
      Kv1.3, particularly at the membrane surface, and subsequently eliminated the BDNF
      induced phosphorylation of Kv1.3. To examine the possibility that the Src
      homology 2 (SH2) domains of Grb10 were directly binding to basally phosphorylated
      tyrosines in Kv1.3, we utilized point mutations to substitute multiple tyrosine
      residues with phenylalanine. Removal of the tyrosines 111-113 and 449 prevented
      Grb10 from decreasing Kv1.3 expression. In the absence of either adaptor protein,
      channel co-expression reciprocally down-regulated expression and tyrosine
      phosphorylation of TrkB kinase and related insulin receptor kinase. Finally,
      through patch-clamp electrophysiology, we found that the BDNF-induced current
      suppression of the channel was prevented by both nShc and Grb10. CONCLUSION: We
      report that adaptor protein alteration of kinase-induced Kv1.3 channel modulation
      is related to the degree of direct protein-protein association and that the
      channel itself can reciprocally modulate receptor-linked tyrosine kinase
      expression and activity.

PMID- 19166617
TI  - Competitive assembly of South Pacific invasive ant communities.
AB  - BACKGROUND: The relative importance of chance and determinism in structuring
      ecological communities has been debated for nearly a century. Evidence for
      determinism or assembly rules is often evaluated with null models that randomize
      the occurrence of species in particular locales. However, analyses of the
      presence or absence of species ignores the potential influence of species
      abundances, which have long been considered of major importance on community
      structure. Here, we test for community assembly rules in ant communities on small
      islands of the Tokelau archipelago using both presence-absence and abundance
      data. We conducted three sets of analyses on two spatial scales using three years
      of sampling data from 39 plots on 11 islands. RESULTS: First, traditional null
      model tests showed support for negative species co-occurrence patterns among
      plots within islands, but not among islands. A plausible explanation for this
      result is that analyses at larger spatial scales merge heterogeneous habitats
      that have considerable effects on species occurrences. Second, analyses of ant
      abundances showed that samples with high ant abundances had fewer species than
      expected by chance, both within and among islands. One ant species, the invasive
      yellow crazy ant Anoplolepis gracilipes, appeared to have a particularly strong
      effect on community structure correlated with its abundance. Third, abundances of
      most ant species were inversely correlated with the abundances of all other ants
      at both spatial scales. This result is consistent with competition theory, which
      predicts species distributions are affected by diffuse competition with suites of
      co-occurring species. CONCLUSION: Our results support a pluralistic explanation
      for ant species abundances and assembly. Both stochastic and deterministic
      processes interact to determine ant community assembly, though abundance patterns
      clearly drive the deterministic patterns in this community. These deterministic
      patterns were observed at two spatial scales. Results indicate that abundance
      based null models may be more sensitive in detecting non-random patterns in
      community assembly than species co-occurrences analyses.

PMID- 19166616
TI  - Characteristics of acute congestive heart failure with normal ejection fraction
      and less elevated B-type natriuretic peptide.
AB  - BACKGROUND: Heterogeneity in B-type natriuretic peptide (BNP) levels, especially
      among individuals with acute heart failure with normal left ventricular ejection
      fraction (HFNEF), can cause confusion in interpreting results. We investigated
      the characteristics of cases of acute HFNEF with only modestly elevated BNP.
      METHODS: One hundred forty-two patients with acute or acute exacerbation of
      chronic HFNEF were divided into two groups by BNP level: BNP < 100 pg/ml (NB
      group, n = 45) and BNP > or = 100 pg/ml (B group, n = 97). We compared clinical
      findings, echocardiography results, and neurohormonal factors between these two
      groups. RESULTS: In the NB group, a history of open-heart surgery (OHS) was more
      frequent (71% vs. 22%, p < 0.0001) and hypertension was less frequent (p =
      0.0005). Left atrial diameter (LAd) was higher (p = 0.0026), while
      interventricular septal thickness, posterior wall thickness, relative wall
      thickness, left ventricular mass index were lower (p = 0.0005, p = 0.0225, p =
      0.0114, p = 0.0051, respectively) in the NB group. In patients with HFNEF, a
      history of OHS remained an independent predictor of BNP level (< 100 pg/ml) after
      adjustment for hypertension, age, LAd, and interventricular septal thickness
      (odds ratio 3.6, p = 0.0252). CONCLUSION: We found associations between acute
      HFNEF with less elevated BNP and a history of OHS. In a patient suspected of
      HFNEF, a history of OHS is considered diagnostic evidence of presence of
      diastolic heart failure when plasma levels of BNP are less elevated.

PMID- 19166618
TI  - Do Asian breast cancer patients have poorer survival than their western
      counterparts? A comparison between Singapore and Stockholm.
AB  - INTRODUCTION: The difference in breast cancer incidence and prognosis between
      ethnic groups seeks an explanation. We have recently shown that Swedish women are
      two to three times more likely to be diagnosed with breast cancer compared with
      Singaporean women. In the present paper, we compare breast cancer survival in the
      two countries. METHODS: We compared the survival of 10,287 Singaporean women and
      17,090 Swedish women with breast cancer. Relative survival ratios were used to
      describe the prognosis in the two populations. A Poisson regression model was
      used to calculate relative risks for different follow-up periods, age groups,
      time of diagnosis and disease stages. RESULTS: The majority of the Swedish women
      had local cancer (80%) compared with Singaporean women (51%). The overall 5-year
      relative survival of the Swedish women appeared better (80%) than that of the
      Singaporean women (70%). A similar survival pattern was observed, however,
      between the two countries in a stage-by-stage comparison. Survival improved for
      all women in Singapore over the two decades, but only in the premenopausal women
      in Stockholm. In 1980 to 1989, premenopausal Singaporean women had 27% increased
      risk of death compared with Swedish women, adjusted for stage and year of follow
      up, while the postmenopausal women had 48% increased risk. In 1990 to 1999, this
      risk decreased by 19% and 22% for the premenopausal and postmenopausal
      Singaporean women compared with the Swedish women. CONCLUSIONS: The stage
      dependent prognosis was similar for Singaporean women and for Swedish women.
      Singaporean women, both premenopausal and postmenopausal, had pronounced
      improvement in prognosis over the calendar periods, probably contributed by
      marked economic improvement, leading to better medical facilities and management
      with increased awareness of patients to diagnosis and treatment, as well as
      improved treatment options. Improvement seen only in the premenopausal women in
      Stockholm was probably due to improved treatment options.

PMID- 19166619
TI  - Extramedullary leukemia in children presenting with proptosis.
AB  - BACKGROUND: We highlight the orbital manifestations of acute myeloid leukemia and
      the role of peripheral blood smear in the diagnosis of these cases. A total of 12
      patients who presented with proptosis and were subsequently diagnosed to have
      acute myeloid leukemia based on incision biopsy or peripheral blood smear were
      included in the study. RESULTS: A retrospective review of all cases of acute
      myeloid leukemia presenting to the Orbital clinic was performed. The age at
      presentation, gender, presenting features, duration of symptoms and fundus
      features were noted. In addition the temporal relationship of the orbital disease
      to the diagnosis of leukemia, laterality, location of the orbital mass, imaging
      features and the diagnostic tools used to diagnose leukemia were noted. The
      median age at presentation was 6 years. The male: female ratio was 0.7:1. None of
      these patients had been diagnosed earlier as having acute myeloid leukemia. The
      presenting features included proptosis in all patients, orbital mass in 5
      (41.7%), visual symptoms in 2 (16.7%) and subconjunctival hemorrhage in one
      patient (8.3%). A diagnosis of acute myeloid leukemia was established by incision
      biopsy in 4 patients, subsequently confirmed by peripheral blood smear testing
      and bone marrow biopsy in 2 patients which revealed the presence of systemic
      involvement. Imprint smears of the biopsy identified blasts in 2 of 4 cases. In 8
      patients presenting with ocular manifestations, diagnosis was established by
      peripheral blood smear examination alone which revealed a diagnosis of acute
      myeloid leukemia. CONCLUSION: A peripheral blood smear should be performed in all
      cases of sudden onset proptosis or an orbital mass in children and young adults
      along with an orbital biopsy. It can always be complemented with a bone marrow
      biopsy especially in cases of aleukemic leukemia or when the blood smear is
      inconclusive.

PMID- 19166620
TI  - Patterns of exon-intron architecture variation of genes in eukaryotic genomes.
AB  - BACKGROUND: The origin and importance of exon-intron architecture comprises one
      of the remaining mysteries of gene evolution. Several studies have investigated
      the variations of intron length, GC content, ordinal position in a gene and
      divergence. However, there is little study about the structural variation of
      exons and introns. RESULTS: We investigated the length, GC content, ordinal
      position and divergence in both exons and introns of 13 eukaryotic genomes,
      representing plant and animal. Our analyses revealed that three basic patterns of
      exon-intron variation were present in nearly all analyzed genomes (P < 0.001 in
      most cases): an ordinal reduction of length and divergence in both exon and
      intron, a co-variation between exon and its flanking introns in their length, GC
      content and divergence, and a decrease of average exon (or intron) length, GC
      content and divergence as the total exon numbers of a gene increased. In
      addition, we observed that the shorter introns had either low or high GC content,
      and the GC content of long introns was intermediate. CONCLUSION: Although the
      factors contributing to these patterns have not been identified, our results
      provide three important clues: common factor(s) exist and may shape both exons
      and introns; the ordinal reduction patterns may reflect a time-orderly evolution;
      and the larger first and last exons may be splicing-required. These clues provide
      a framework for elucidating mechanisms involved in the organization of eukaryotic
      genomes and particularly in building exon-intron structures.

PMID- 19166621
TI  - The intraportal injection model: a practical animal model for hepatic metastases
      and tumor cell dissemination in human colon cancer.
AB  - BACKGROUND: The development of new therapeutic strategies for treatment of
      metastasized colorectal carcinoma requires biologically relevant and adequate
      animal models that generate both reproducible metastasis and the dissemination of
      tumor cells in the form of so-called minimal residual disease (MRD), an
      expression of the systemic character of neoplastic disease. METHODS: We injected
      immunoincompetent nude mice intraportally with different numbers (1 x 10(5), 1 x
      10(6) and 5 x 10(6) cells) of the human colon carcinoma cell lines HT-29 and SW
      620 and investigated by histological studies and CK-20 RT-PCR the occurrence of
      hematogenous metastases and the dissemination of human tumor cells in bone
      marrow. RESULTS: Only the injection of 1 x 10(6) cells of each colon carcinoma
      cell line produced acceptable perioperative mortality with reproducible induction
      of hepatic metastases in up to 89% of all animals. The injection of 1 x 10(6)
      cells also generated tumor cell dissemination in the bone marrow in up to 63% of
      animals with hepatic metastases. CONCLUSION: The present intraportal injection
      model in immunoincompetent nude mice represents a biologically relevant and
      adequate animal model for the induction of both reproducible hepatic metastasis
      and tumor cell dissemination in the bone marrow as a sign of MRD.

PMID- 19166622
TI  - Epidemiology of frequent attenders: a 3-year historic cohort study comparing
      attendance, morbidity and prescriptions of one-year and persistent frequent
      attenders.
AB  - BACKGROUND: General Practitioners spend a disproportionate amount of time on
      frequent attenders. So far, trials on the effect of interventions on frequent
      attenders have shown negative results. However, these trials were conducted in
      short-term frequent attenders. It would be more reasonable to target intervention
      at persistent frequent attenders. Typical characteristics of persistent frequent
      attenders, as opposed to 1-year frequent attenders and non-frequent attenders,
      may generate hypotheses regarding modifiable factors on which new randomized
      trials may be designed. METHODS: We used the data of all 28,860 adult patients
      from 5 primary healthcare centers. Frequent attenders were patients whose
      attendance rate ranked in the (age and sex adjusted) top 10 percent during 1 year
      (1-year frequent attenders) or 3 years (persistent frequent attenders). All other
      patients on the register over the 3-year period were referred to as non-frequent
      attenders. The lists of medical problems coded by the GP using the International
      Classification of Primary Care (ICPC) were used to assess morbidity.First, we
      determined which proportion of 1-year frequent attenders was still a frequent
      attender during the next two consecutive years and calculated the GPs' workload
      for these patients. Second, we compared morbidity and number of prescriptions for
      non-frequent attenders, 1-year frequent attenders and persistent frequent
      attenders. RESULTS: Of all 1-year frequent attenders, 15.4% became a persistent
      frequent attender equal to 1.6% of all patients. The 1-year frequent attenders
      (3,045; 10.6%) were responsible for 39% of the face-to-face consultations; the
      470 patients who would become persistent frequent attenders (1.6%) were
      responsible for 8% of all consultations in 2003. Persistent frequent attenders
      presented more social problems, more psychiatric problems and medically
      unexplained physical symptoms, but also more chronic somatic diseases (especially
      diabetes). They received more prescriptions for psychotropic medication.
      CONCLUSION: One out of every seven 1-year-frequent attenders (15.4%) becomes a
      persistent frequent attender. Compared with non-frequent attenders, and 1-year
      frequent attenders, persistent frequent attenders consume more health care and
      are diagnosed not only with more somatic diseases but especially more social
      problems, psychiatric problems and medically unexplained physical symptoms.

PMID- 19166623
TI  - Benefits of intensive insulin therapy on neuromuscular complications in routine
      daily critical care practice: a retrospective study.
AB  - INTRODUCTION: Intensive insulin therapy (IIT) reduced the incidence of critical
      illness polyneuropathy and/or myopathy (CIP/CIM) and the need for prolonged
      mechanical ventilation (MV >or= 14 days) in two randomised controlled trials
      (RCTs) on the effect of IIT in a surgical intensive care unit (SICU) and medical
      intensive care unit (MICU). In the present study, we investigated whether these
      effects are also present in daily clinical practice when IIT is implemented
      outside of a study protocol. METHODS: We retrospectively studied
      electrophysiological data from patients in the SICU and MICU, performed because
      of clinical weakness and/or weaning failure, before and after routine
      implementation of IIT. CIP/CIM was diagnosed by abundant spontaneous electrical
      activity on electromyography. Baseline and outcome variables were compared using
      Student's t-test, Chi-squared or Mann-Whitney U-test when appropriate. The effect
      of implementing IIT on CIP/CIM and prolonged MV was assessed using univariate
      analysis and multivariate logistic regression analysis (MVLR), correcting for
      baseline and ICU risk factors. RESULTS: IIT significantly lowered mean (+/-
      standard deviation) blood glucose levels (from 144 +/- 20 to 107 +/- 10 mg/dl, p
      < 0.0001) and significantly reduced the diagnosis of CIP/CIM in the screened long
      stay patients (125/168 (74.4%) to 220/452 (48.7%), p < 0.0001). MVLR identified
      implementing IIT as an independent protective factor (p < 0.0001, odds ratio
      (OR): 0.25 (95% confidence interval (CI): 0.14 to 0.43)). MVLR confirmed the
      independent protective effect of IIT on prolonged MV (p = 0.002, OR:0.40 (95% CI:
      0.22-0.72)). This effect was statistically only partially explained by the
      reduction in CIP/CIM. CONCLUSIONS: Implementing IIT in routine daily practice in
      critically ill patients evoked a similar beneficial effect on neuromuscular
      function as that observed in two RCTs. IIT significantly improved glycaemic
      control and significantly and independently reduced the electrophysiological
      incidence of CIP/CIM. This reduction partially explained the beneficial effect of
      IIT on prolonged MV.

PMID- 19166624
TI  - VASCo: computation and visualization of annotated protein surface contacts.
AB  - BACKGROUND: Structural data from crystallographic analyses contain a vast amount
      of information on protein-protein contacts. Knowledge on protein-protein
      interactions is essential for understanding many processes in living cells. The
      methods to investigate these interactions range from genetics to biophysics,
      crystallography, bioinformatics and computer modeling. Also crystal contact
      information can be useful to understand biologically relevant protein
      oligomerisation as they rely in principle on the same physico-chemical
      interaction forces. Visualization of crystal and biological contact data
      including different surface properties can help to analyse protein-protein
      interactions. RESULTS: VASCo is a program package for the calculation of protein
      surface properties and the visualization of annotated surfaces. Special emphasis
      is laid on protein-protein interactions, which are calculated based on surface
      point distances. The same approach is used to compare surfaces of two aligned
      molecules. Molecular properties such as electrostatic potential or hydrophobicity
      are mapped onto these surface points. Molecular surfaces and the corresponding
      properties are calculated using well established programs integrated into the
      package, as well as using custom developed programs. The modular package can
      easily be extended to include new properties for annotation. The output of the
      program is most conveniently displayed in PyMOL using a custom-made plug-in.
      CONCLUSION: VASCo supplements other available protein contact visualisation tools
      and provides additional information on biological interactions as well as on
      crystal contacts. The tool provides a unique feature to compare surfaces of two
      aligned molecules based on point distances and thereby facilitates the
      visualization and analysis of surface differences.

PMID- 19166625
TI  - Mechanisms employed by retroviruses to exploit host factors for translational
      control of a complicated proteome.
AB  - Retroviruses have evolved multiple strategies to direct the synthesis of a
      complex proteome from a single primary transcript. Their mechanisms are modulated
      by a breadth of virus-host interactions, which are of significant fundamental
      interest because they ultimately affect the efficiency of virus replication and
      disease pathogenesis. Motifs located within the untranslated region (UTR) of the
      retroviral RNA have established roles in transcriptional trans-activation, RNA
      packaging, and genome reverse transcription; and a growing literature has
      revealed a necessary role of the UTR in modulating the efficiency of viral
      protein synthesis. Examples include a 5' UTR post-transcriptional control element
      (PCE), present in at least eight retroviruses, that interacts with cellular RNA
      helicase A to facilitate cap-dependent polyribosome association; and 3' UTR
      constitutive transport element (CTE) of Mason-Pfizer monkey virus that interacts
      with Tap/NXF1 and SR protein 9G8 to facilitate RNA export and translational
      utilization. By contrast, nuclear protein hnRNP E1 negatively modulates HIV-1
      Gag, Env, and Rev protein synthesis. Alternative initiation strategies by
      ribosomal frameshifting and leaky scanning enable polycistronic translation of
      the cap-dependent viral transcript. Other studies posit cap-independent
      translation initiation by internal ribosome entry at structural features of the
      5' UTR of selected retroviruses. The retroviral armamentarium also commands
      mechanisms to counter cellular post-transcriptional innate defenses, including
      protein kinase R, 2',5'-oligoadenylate synthetase and the small RNA pathway. This
      review will discuss recent and historically-recognized insights into retrovirus
      translational control. The expanding knowledge of retroviral post-transcriptional
      control is vital to understanding the biology of the retroviral proteome. In a
      broad perspective, each new insight offers a prospective target for antiviral
      therapy and strategic improvement of gene transfer vectors.

PMID- 19166626
TI  - Seven new dolphin mitochondrial genomes and a time-calibrated phylogeny of
      whales.
AB  - BACKGROUND: The phylogeny of Cetacea (whales) is not fully resolved with
      substantial support. The ambiguous and conflicting results of multiple
      phylogenetic studies may be the result of the use of too little data,
      phylogenetic methods that do not adequately capture the complex nature of DNA
      evolution, or both. In addition, there is also evidence that the generic taxonomy
      of Delphinidae (dolphins) underestimates its diversity. To remedy these problems,
      we sequenced the complete mitochondrial genomes of seven dolphins and analyzed
      these data with partitioned Bayesian analyses. Moreover, we incorporate a newly
      developed "relaxed" molecular clock to model heterogenous rates of evolution
      among cetacean lineages. RESULTS: The "deep" phylogenetic relationships are well
      supported including the monophyly of Cetacea and Odontoceti. However, there is
      ambiguity in the phylogenetic affinities of two of the river dolphin clades
      Platanistidae (Indian River dolphins) and Lipotidae (Yangtze River dolphins). The
      phylogenetic analyses support a sister relationship between Delphinidae and
      Monodontidae + Phocoenidae. Additionally, there is statistically significant
      support for the paraphyly of Tursiops (bottlenose dolphins) and Stenella (spotted
      dolphins). CONCLUSION: Our phylogenetic analysis of complete mitochondrial
      genomes using recently developed models of rate autocorrelation resolved the
      phylogenetic relationships of the major Cetacean lineages with a high degree of
      confidence. Our results indicate that a rapid radiation of lineages explains the
      lack of support the placement of Platanistidae and Lipotidae. Moreover, our
      estimation of molecular divergence dates indicates that these radiations occurred
      in the Middle to Late Oligocene and Middle Miocene, respectively. Furthermore, by
      collecting and analyzing seven new mitochondrial genomes, we provide strong
      evidence that the delphinid genera Tursiops and Stenella are not monophyletic,
      and the current taxonomy masks potentially interesting patterns of morphological,
      physiological, behavioral, and ecological evolution.

PMID- 19166628
TI  - Short rotator tendons do not increase intracapsular pressure in severe
      osteoarthritic hips.
AB  - BACKGROUND: While a relation between pain and intracapsular pressure in the hip
      joint has previously been reported by some of the present authors, a newly
      published study including patients with severe osteoarthritis was not able to
      confirm this finding. This stimulated us to investigate the role of short
      rotators in relation to intracapsular pressure and pain in osteoarthritic hips.
      METHODS: We measured the intracapsular hydrostatic pressure peroperatively in 25
      total hip arthroplasty patients with severe osteoarthritis in various positions
      of the hip joint before and after short rotator release, and correlated these
      pressures to pain. RESULTS: Release of the short rotators did not change the
      intracapsular pressure in any position except in 45 degrees flexion, in which the
      pressure increased (p = 0.002). We found no correlation between intracapsular
      pressure and pain before or after short rotator release. CONCLUSION: We could not
      show that the rotators directly affected the pressure nor could we find a
      relation between pressure and pain.

PMID- 19166629
TI  - Solitary necrotic nodule of the liver mimicking hepatocellular carcinoma: a case
      report.
AB  - INTRODUCTION: Solitary necrotic nodule of the liver is a rare lesion, with
      similar radiologic findings to those of hepatic metastases or other liver masses.
      CASE PRESENTATION: We here report a case of a 30-year-old male with hepatic
      solitary necrotic nodule discovered after an episode of acute abdominal pain and
      high grade fever. Routine laboratory data revealed leukocytosis and abnormal
      liver function. The imaging features of the lesion suggested malignancy or liver
      adenoma. The patient underwent surgical resection of segments V and VI. Histology
      was compatible with solitary necrotic nodule and localized vein thrombosis at the
      periphery. CONCLUSION: Solitary necrotic nodule of the liver is a benign lesion
      which can mimic liver malignancies. Abdominal imaging and liver biopsy are often
      equivocal. In such circumstances liver resection is mandatory to exclude HCC or
      other malignant liver lesions.

PMID- 19166627
TI  - Prevention of non-communicable disease in a population in nutrition transition:
      Tehran Lipid and Glucose Study phase II.
AB  - BACKGROUND: The Tehran Lipid and Glucose Study (TLGS) is a long term integrated
      community-based program for prevention of non-communicable disorders (NCD) by
      development of a healthy lifestyle and reduction of NCD risk factors. The study
      begun in 1999, is ongoing, to be continued for at least 20 years. A primary
      survey was done to collect baseline data in 15005 individuals, over 3 years of
      age, selected from cohorts of three medical heath centers. A questionnaire for
      past medical history and data was completed during interviews; blood pressure,
      pulse rate, and anthropometrical measurements and a limited physical examination
      were performed and lipid profiles, fasting blood sugar and 2-hours-postload
      glucose challenge were measured. A DNA bank was also collected. For those
      subjects aged over 30 years, Rose questionnaire was completed and an
      electrocardiogram was taken. Data collected were directly stored in computers as
      database software- computer assisted system. The aim of this study is to evaluate
      the feasibility and effectiveness of lifestyle modification in preventing or
      postponing the development of NCD risk factors and outcomes in the TLGS
      population. DESIGN AND METHODS: In phase II of the TLGS, lifestyle interventions
      were implemented in 5630 people and 9375 individuals served as controls. Primary,
      secondary and tertiary interventions were designed based on specific target
      groups including schoolchildren, housewives, and high-risk persons. Officials of
      various sectors such as health, education, municipality, police, media, traders
      and community leaders were actively engaged as decision makers and collaborators.
      Interventional strategies were based on lifestyle modifications in diet, smoking
      and physical activity through face-to-face education, leaflets & brochures,
      school program alterations, training volunteers as health team and treating
      patients with NCD risk factors. Collection of demographic, clinical and
      laboratory data will be repeated every 3 years to assess the effects of different
      interventions in the intervention group as compared to control group. CONCLUSION:
      This controlled community intervention will test the possibility of preventing or
      delaying the onset of non-communicable risk factors and disorders in a population
      in nutrition transition. TRIAL REGISTRATION: ISRCTN52588395.

PMID- 19166631
TI  - Early life programming of immune and lung function: can we now exclude a role of
      arachidonic acid exposure?

PMID- 19166630
TI  - Impact of maternal dietary fatty acid composition on glucose and lipid metabolism
      in male rat offspring aged 105 d.
AB  - In recent years the intake of n-6 PUFA and trans-fatty acids (TFA) has increased,
      whereas n-3 PUFA intake has decreased. The present study investigated the effects
      of maternal diet high in n-6 PUFA, n-3 PUFA or TFA on glucose metabolism, insulin
      sensitivity and fatty acid profile in male offspring. Female weanling Wistar/NIN
      rats were randomly assigned to receive either a diet high in linoleic acid (LA),
      or alpha-linolenic acid (ALA), or long-chain n-3 PUFA (fish oil; FO), or TFA, for
      90 d, and mated. Upon weaning, pups were randomly divided into seven groups
      (mother's diet-pup's diet): LA-LA, LA-ALA, LA-FO, ALA-ALA, FO-FO, TFA-TFA and TFA
      LA. At the age of 105 d, an oral glucose tolerance test, adipocyte glucose
      transport and muscle phospholipid fatty acid composition were measured in the
      pups. All animals displayed normal insulin sensitivity as evidenced by similar
      plasma insulin and area under the curve of insulin after an oral glucose load.
      Maternal intake of n-3 PUFA (ALA or FO) resulted in higher n-3 PUFA in the
      offspring. Plasma cholesterol and NEFA were significantly higher in the TFA-TFA
      group compared with the other groups. Adipocyte insulin-stimulated glucose
      transport and adiponectin mRNA expression were lower in TFA-TFA and TFA-LA
      offspring compared with the other groups. While most mother-pup fatty acid
      combinations did not influence the measured variables in the pups, these results
      indicate that maternal intake of TFA led to an unfavourable profile in the pups
      through to the age of 105 d, whether the pups consumed TFA, or not.

PMID- 19166632
TI  - When good nutrients go bad: can we predict nutrient-drug interactions?

PMID- 19166633
TI  - Functional vocal results after CO2 laser endoscopic surgery for glottic tumours.

PMID- 19166634
TI  - Reaction in Ontario to Bill 110: Canada's first mandatory gunshot wound reporting
      law.
AB  - OBJECTIVE: With the proclamation of Bill 110 in September 2005, Ontario became
      the first jurisdiction in Canada to mandate that gunshot wounds (GSWs) be
      reported to authorities. We sought to evaluate the impact of Bill 110, including
      the awareness of, experience with and opinions about the new law among Ontario
      emergency physicians (EPs), the public and the police. METHODS: An online survey
      was distributed to all members of the Section on Emergency Medicine at the
      Ontario Medical Association. The public survey consisted of 3 closed questions
      and was performed by the polling firm Ipsos-Reid by telephone. Police opinion was
      requested through the Ministry of Community Safety and Correctional Services of
      the Ontario government. RESULTS: The physician response rate was 25%. The great
      majority of respondents were aware of the law (93%) and willing to comply (88%),
      but only half were sure of their obligations and the penalties. Since the law had
      been proclaimed, the majority (51%) had seen at least 1 GSW victim. Seventy-nine
      percent reported no problems with either the police or the bill, and 86%
      perceived no change in relations with patients. Six incidents of patients
      delaying care were reported. Of the public surveyed, two-thirds were aware of the
      law. After being informed of the law, almost all (95%) expressed support, and the
      majority (80%) felt it would not change their relationship with their treating
      physician. All 47 members of the Ontario Provincial Police who were surveyed
      agreed that Bill 110 is helpful for shooting investigations, 8 reported that they
      had personally been involved in cases initiated by a report and 6 had been
      involved in cases where charges were laid or weapons confiscated. Data on actual
      reports and results of investigations were not available. CONCLUSION: Bill 110
      seems to have been broadly accepted by the emergency community and endorsed by
      the public.

PMID- 19166636
TI  - Validity of the Canadian Paediatric Triage and Acuity Scale in a tertiary care
      hospital.
AB  - OBJECTIVE: We evaluated the validity of the Canadian Paediatric Triage and Acuity
      Scale (PaedCTAS) for children visiting a pediatric emergency department (ED).
      METHODS: This was a retrospective study evaluating all children who presented to
      a pediatric university-affiliated ED during a 1-year period. Data were retrieved
      from the ED database. Information regarding triage and disposition was registered
      in an ED database by a clerk following patient management. In the absence of a
      gold standard for triage, admission to hospital, admission to pediatric intensive
      care unit (PICU) and length of stay (LOS) in the ED were used as surrogate
      markers of severity. The primary outcome measure was the correlation between
      triage level (from 1 to 5) and admission to hospital. The correlation between
      triage level and dichotomous outcomes was evaluated by a chi2 test and an
      analysis of variance (ANOVA) was used to evaluate the association between triage
      level and ED LOS. RESULTS: Over the 1-year period, 58,529 patients were triaged
      in the ED. The proportion admitted to hospital was 63% for resuscitation (level
      1), 37% for emergent (level 2), 14% for urgent (level 3), 2% for semiurgent
      (level 4) and 1% for nonurgent (level 5) (p < 0.001). There was also a good
      correlation between triage levels and LOS and admission to PICU (both p < 0.001).
      CONCLUSION: This computerized version of PaedCTAS demonstrates a string
      association with admission to hospital, admission to PICU and LOS in the ED.
      These results suggest that PaedCTAS is a valid tool for triage of children in a
      pediatric ED.

PMID- 19166635
TI  - Association of injury mechanism with the risk of cervical spine fractures.
AB  - OBJECTIVE: A full understanding of an injury event and the mechanical forces
      involved should be important for predicting specific anatomical patterns of
      injury. Yet, information on the mechanism of injury is often overlooked as a
      predictor for specific anatomical injury in clinical decision-making. We measured
      the relationship between mechanism of injury and risk for cervical spine
      fracture. METHODS: Our case-control study is a secondary analysis of data
      collected from the Canadian C-Spine Rule (CCR) study. Data were collected from
      1996 to 2002 and included patients presenting to the emergency departments of 9
      tertiary care centres after sustaining acute blunt trauma to the head or neck.
      Cases are defined as patients who were categorized in the CCR study with a
      clinically important cervical spine fracture. Controls had no radiologic evidence
      of cervical spine injury. Bivariate and multivariate unconditional logistic
      regression models were used. Results are presented as odds ratios (ORs) with 95%
      confidence intervals (CIs). RESULTS: Among the 17,208 patients in the CCR study,
      320 (2%)received a diagnosis of a cervical spine fracture. Axial loads, falls,
      diving incidents and nontraffic motorized vehicle collisions (e.g., collisions
      involving snowmobiles or all-terrain vehicles) were injury mechanisms that were
      significantly related to a higher risk of fracture. For motor vehicle collisions,
      the risk of cervical spine injury increased with the posted speed, being involved
      in a head-on collision or a rollover, or not wearing a seat belt (p < 0.05). The
      occurrence of cervical spine fracture was negligible in simple rear-end
      collisions (1 in 3694 cases; OR 0.015, 95% CI 0.002-0.104]). CONCLUSION: Our
      study quantitatively demonstrates the relationship between specific mechanisms of
      injury and the risk of a cervical spine fracture. A full understanding of the
      injury mechanism would assist providers of emergency health care in assessing
      risk for injury in trauma patients.

PMID- 19166637
TI  - Impact of a rapid access protocol on decreasing door-to-balloon time in acute ST
      elevation myocardial infarction.
AB  - OBJECTIVE: Ischemic cardiovascular disease is the leading cause of death in
      Canada. In ST elevation myocardial infarction (STEMI), time to reperfusion is a
      key determinant in reducing morbidity and mortality with percutaneous coronary
      intervention (PCI) being the preferred reperfusion strategy. Where PCI is
      available, delays to definitive care include times to electrocardiogram (ECG)
      diagnosis and cardiovascular laboratory access. In 2004, the Cardiac Care Network
      of Ontario recommended implementation of an emergency department (ED) protocol to
      reduce reperfusion time by transporting patients with STEMI directly to the
      nearest catheterization laboratory. The model was implemented in Frontenac County
      in April 2005. The objective of this study was to assess the effectiveness of a
      protocol for rapid access to PCI in reducing door-to-balloon times in STEMI.
      METHODS: Two 1-year periods before and after implementation of a rapid access to
      PCI protocol (ending March 2005 and June 2006, respectively) were studied.
      Administrative databases were used to identify all subjects with STEMI who were
      transported by regional emergency medical services (EMS) and received emergent
      PCI. The primary outcome measure was time from ED arrival to first balloon
      inflation (door-to-balloon time). Times are presented as medians and
      interquartile ranges (IQRs). Statistical comparisons were made using the Mann
      Whitney U test and presented graphically with Kaplan-Meier curves. RESULTS:
      Patients transported under the rapid access protocol (n = 39) were compared with
      historical controls (n = 42). Median door-to-balloon time was reduced from 87
      minutes (IQR 67-108) preprotocol to 62 minutes (IQR 40-80) postprotocol (p <
      0.001). CONCLUSION: In our region, implementation of an EMS protocol for rapid
      access to PCI significantly reduced time to reperfusion for patients with STEMI.

PMID- 19166638
TI  - Refinement of the Quebec decision rule for radiography in shoulder dislocation.
AB  - OBJECTIVE: We prospectively derived a clinical decision rule to guide pre- and
      postreduction radiography for emergency department (ED) patients with anterior
      glenohumeral dislocation. METHODS: This prospective cohort derivation study took
      place at 4 university-affiliated EDs over a 3-year period and enrolled consenting
      patients with anterior glenohumeral dislocation who were 18 years of age or
      older. We compared patients with a clinically important fracture-dislocation with
      those who had an uncomplicated dislocation to provide the clinical decision rule
      components using recursive partitioning. The final rule involved age, mechanism,
      prior dislocation and humeral ecchymosis. RESULTS: A total of 222 patients were
      included in the study. Forty (18.0%) had clinically important fracture
      dislocation. A clinical decision rule using 4 factors reached a sensitivity of
      100% (95% confidence interval [CI] 89.4%-100%), a specificity of 34.2% (95% CI
      27.7%-41.2%), a negative predictive value of 99.2% (95% CI 92.8%-99.9%) and a
      negative likelihood ratio of 0.04 (95% CI 0.002-0.27). Patients younger than 40
      years are at high risk for clinically important fracture- dislocation only if the
      mechanism of injury involves substantial force (i.e., a fall greater than their
      own height, a sport injury, an assault or a motor vehicle collision). Patients 40
      years of age or older are at high risk only in the presence of humeral ecchymosis
      or after their first dislocation. Projected use of the rule would reduce the
      absolute number of prereduction radiographs by 27.9% and of postreduction by
      81.9%. CONCLUSION: The Quebec shoulder dislocation rule for patients with acute
      anterior glenohumeral dislocation holds promise to reduce unnecessary imaging,
      pending validation.

PMID- 19166639
TI  - Use of personal protective equipment during infectious disease outbreak and
      nonoutbreak conditions: a survey of emergency medical technicians.
AB  - OBJECTIVE: We sought to assess the knowledge of, use of and barriers to the use
      of personal protective equipment for airway management among emergency medical
      technicians (EMTs) during and since the 2003 Canadian outbreak of Severe Acute
      Respiratory Syndrome (SARS). METHODS: Using a cross-sectional survey, EMTs in
      Toronto, Ont., were surveyed 1 year after the SARS outbreak during mandatory
      training on the use of personal protective equipment in airway management during
      the outbreak and just before taking the survey. Practices that were addressed
      reflected government directives on the use of this equipment. Main outcome
      measures included the frequency of personal protective equipment use and, as
      applicable, why particular items were not always used. RESULTS: The response rate
      was 67.3% (n = 230). During the SARS outbreak, an N95-type particulate respirator
      was reported to be always used by 91.5% of respondents. Conversely, 72.9% of the
      respondents reported that they never used the open face hood. Equipment
      availability and vision impairment were often cited as impediments to personal
      protective equipment use. In nonoutbreak conditions, only the antimicrobial
      airway filter was most often reported to be always used (52.0%), while other
      items were used at an intermediate frequency. The most common reason for not
      always donning equipment was that paramedics deemed it unnecessary for the
      situation. CONCLUSION: Personal protective equipment is not consistently employed
      as per medical directives. Reasons given for nonuse included nonavailability,
      judgment of nonnecessity or technical difficulties. There are important public
      health implications of noncompliance.

PMID- 19166640
TI  - A prospective study of students' and instructors' opinions on Advanced Cardiac
      Life Support course teaching methods.
AB  - INTRODUCTION: The American Heart Association (AHA) revises the Advanced Cardiac
      Life Support (ACLS) course approximately every 5 years, citing the scientific
      literature for any changes to content and management recommendations. With ACLS
      2005, the AHA also revised the methods used to teach course content. The AHA
      cited no evidence in making these changes. The ACLS 2005 course, distributed in
      early 2007, makes greater use of videos to teach students. This prospective study
      surveyed opinions of both students and instructors in an effort to determine the
      level of satisfaction with this method of teaching. METHODS: During 16
      consecutive ACLS courses, all students and instructors were asked to complete a
      questionnaire. The students provided demographic information, but completed the
      survey anonymously. Four questions probed the participants' opinions about the
      effectiveness of videos in learning ACLS skills. Experienced participants were
      asked to compare the new teaching methods with previous courses. Opinions were
      compared among several subgroups based on sex, occupation and previous
      experience. RESULTS: Of the 180 students who participated, 71% felt the videos
      were unequivocally useful for teaching ACLS skills. Fewer first-time students
      were unequivocally positive (59%) compared with those who had taken 2 or more
      previous courses (84%). A small proportion of students (13%) desired more hands
      on practice time. Of the 16 instructors who participated, 31% felt that the
      videos were useful for teaching ACLS skills. No differences were found between
      doctors and nurses, or between men and women. CONCLUSION: The use of standardized
      videos in ACLS courses was felt by the majority of students and a minority of
      instructors to be unequivocally useful. First-time students had more doubts about
      the effectiveness of videos.

PMID- 19166641
TI  - CAEP position statement on gun control.

PMID- 19166643
TI  - Public risk from tasers: unacceptably high or low enough to accept?

PMID- 19166645
TI  - Ophthalmic injuries from a TASER.
AB  - The TASER (TASER International) is an energy-conducting weapon, that is becoming
      more frequently used by law enforcement officials to subdue combative
      individuals. Though generally regarded as a safe alternative, the use of such
      weapons has been reported to cause serious injuries. We describe a case in which
      ocular injuries were sustained by impalement with a TASER dart. Emergency
      physicians should be aware of the potential for serious ophthalmic injuries from
      TASERs and how such injuries should be managed.

PMID- 19166646
TI  - Glycyrrhizic acid toxicity caused by consumption of licorice candy cigars.
AB  - A 49-year-old female physician presented with peripheral edema, weight gain and
      relative hypertension caused by the consumption of licorice candy cigars
      containing glycyrrhizic acid (GZA) found in natural licorice extract. Although
      the patient's response to GZA resolved spontaneously, emergency physician
      awareness of the toxic effects of natural licorice extract may avert symptom
      progression in early-identified cases. The benefits of natural licorice extract
      as a flavour enhancer and herbal medicine are recognized worldwide. The Canadian
      public is likely not generally aware of the toxic potential of GZA, or that it
      may be present in the following commonly consumed products: black licorice,
      chewing gum, herbal teas, soft drinks, tobaccos and herbal remedies for cough,
      stomach ailments and constipation. Emergency physicians should inquire about the
      consumption of products that may contain natural licorice extract when patients
      present with unexplained hypertension, hypokalemia, edema, rhabdomyolysis or
      myoglobinuria.

PMID- 19166647
TI  - The room.

PMID- 19166648
TI  - Health advocacy in emergency medicine: a resident's perspective.

PMID- 19166649
TI  - Triage: going full circle? Hopefully.

PMID- 19166652
TI  - Lack of efficacy of maintenance interferon: results of the HALT-C Trial.

PMID- 19166653
TI  - Role of growth factors and thrombopoietic agents in the treatment of chronic
      hepatitis C.
AB  - Advanced liver disease and interferon-based treatment are both associated with
      varying degrees of cytopenia in patients with chronic hepatitis C. Growth factors
      to increase hemoglobin and neutrophils are commonly used in clinical practice,
      despite the absence of data to indicate benefits in terms of sustained viral
      response. Thrombocytopenia is observed frequently, is multi-factorial in
      etiology, and may result in significant limitations on interventional and
      therapeutic options. A small-molecule thrombopoietin mimetic, eltrombo-pag, has
      demonstrated a dose-response associated increase in platelet count in a phase 2
      study, allowing initiation and completion of a 12-week course of peginterferon
      plus ribavirin in 36%, 53%, and 65% of patients receiving 30 mg, 50 mg, or 75 mg
      of eltrombopag daily, respectively, compared with 6% in the placebo arm. Phase 3
      studies are currently evaluating whether initiating and maintaining antiviral
      therapy with eltrombopag will lead to an increase in sustained virologic response
      in chronic hepatitis C infection.

PMID- 19166654
TI  - Treatment of chronic hepatitis C: anticipated impact of resistance in patients
      treated with protease inhibitors.
AB  - A main target of specifically targeted antiviral therapy for hepatitis C (STAT-C)
      is the NS3-protease, which has key functions in the hepatitis C virus (HCV)
      replication cycle. HCV/NS3-protease inhibitors have shown high antiviral activity
      in vitro and in patients with chronic hepatitis C. Protease-resistant HCV
      variants occurred rapidly in patients receiving protease-inhibitor monotherapy.
      The development of resistance can be best explained by selection of preexisting
      resistant variants, which grow out under selective pressure. Numerous mutations
      associated with resistance were identified. Clinical trials showed that protease
      resistant strains are sensitive to interferon and that a triple combination of
      protease inhibitors, peginterferon, and ribavirin may improve the sustained
      virologic response rate compared with standard peginterferon/ribavirin
      combination therapy. Overall, it can be anticipated that successful treatment
      with protease inhibitors will require either combination therapy with
      peginterferon/ribavirin or a combination of STAT-C compounds with distinct modes
      of action and resistance patterns.

PMID- 19166655
TI  - Treatment of chronic hepatitis B: are we ready for combination therapy?
AB  - Treatment of chronic hepatitis B virus (HBV) infection currently involves the use
      of immunomodulators such as interferon and nucleoside or nucleotide analogues.
      Treatment aims to suppress levels of HBV DNA and induce clearance of the
      hepatitis B e antigen (HBeAg) or surface antigen (HBsAg) and seroconversion. At
      present, no single treatment has been shown to reliably suppress HBV DNA and
      induce durable HBsAg loss. Nucleoside or nucleotide analogues induce the
      production of HBV-resistant mutations that may lead to virologic and clinical
      breakthrough. Combination therapy, using either immunomodulators in combination
      or with nucleoside or nucleotide analogues, represents an emerging strategy for
      treating chronic HBV infection. The theoretical benefits of combining agents with
      varying mechanisms of action include more efficacious viral suppression and
      potentially durable HBsAg loss. Although combination therapy has proven
      successful in chronic hepatotropic viral infections and in chronic, noninfectious
      medical conditions, its benefits must be weighed against risks such as increased
      toxicity, resistance, and cost.

PMID- 19166656
TI  - Role of combination therapy in chronic hepatitis B.
AB  - Combination therapy includes the use of two or more antivirals for the treatment
      of chronic hepatitis B. No study has shown that combination therapy is superior
      to monotherapy in naive patients for achieving treatment end points, but
      combination appears to result in a lower incidence of resistance. Moreover, the
      higher-potency compounds have not yet been studied. Consideration should be given
      to treating lamivudine-resistant patients with combination therapy, preferably
      with a nucleotide analogue in conjunction with a nucleoside analogue. Combination
      therapy should be considered in patients with decompensated cirrhosis who are
      unable to achieve an undetectable viral level on monotherapy and in naive
      patients who still have a detectable viral level 6 to 12 months after starting
      therapy.

PMID- 19166657
TI  - Small-duct primary sclerosing cholangitis.
AB  - Patients with cholestatic liver tests and typical histologic features of primary
      sclerosing cholangitis (PSC) but a normal cholangiogram have been identified as
      having small-duct PSC. This subgroup of PSC has been less well characterized than
      the classic large-duct form. Some patients characterized as having small-duct PSC
      develop cholangiographic features of PSC during follow-up. Three papers published
      in 2002 on small-duct PSC patients suggested a better prognosis in patients with
      small-duct PSC than in those with large-duct PSC. However, these studies included
      a limited number of patients and had a short follow-up. A combined cohort of
      these patients with a prolonged follow-up recently confirmed these previous
      observations. However, some patients will suffer from liver-related mortality or
      will need to undergo liver transplantation. Recurrence of small-duct PSC after
      liver transplantation has been reported. Cholangiocarcinoma, the most feared
      complication of PSC, has not been described in a patient with small-duct PSC
      without progression first to large-duct PSC.

PMID- 19166658
TI  - Granulomatous liver disease.
AB  - Hepatic granulomas are often encountered on liver biopsy and may represent a
      primary hepatic process, a manifestation of a systemic illness, or an innocent
      finding of no clinical relevance. Hepatic granulomas are a unique inflammatory
      response that may be idiopathic or may be a response to a bacterial, fungal,
      viral, or parasitic infection; a manifestation of drug-induced liver injury; or a
      manifestation of underlying malignancy. When granulomas are found on liver
      biopsy, clinicians must correlate the histologic findings with historical and
      clinical data to help provide an accurate diagnosis and guide management. Therapy
      may be warranted, either directly for the granulomatous inflammation of the liver
      or for a systemic process. For some patients, observation may be the most
      appropriate form of management.

PMID- 19166659
TI  - Nonalcoholic fatty liver disease and cardiovascular risk.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a very common cause of chronic liver
      disease in the United States. A large proportion of patients with NAFLD have
      coexisting metabolic syndrome, a major risk factor for cardiovascular disease. A
      strong association between NAFLD and cardiovascular disease has been long
      suspected, and recent studies have confirmed that cardiovascular disease is the
      single most important cause of mortality in this patient population. NAFLD may
      pose cardiovascular risk beyond the risk conferred by traditional factors such as
      dyslipidemia, diabetes, and smoking. Health care providers managing patients with
      NAFLD should recognize this increased cardiovascular risk and should undertake
      early, aggressive risk factor modification.

PMID- 19166660
TI  - Portopulmonary hypertension.
AB  - It has been widely accepted that development of porto-pulmonary hypertension
      (POPH) is independent of the cause of portal hypertension. The degree of hepatic
      damage and liver function do not correlate with predisposition to POPH or its
      severity. However, portal hypertension has been confirmed as a prerequisite for
      developing pulmonary hypertension. Transthoracic echocardiography is the best
      screening test for the presence of POPH, but a diagnosis of POPH can be
      established only by right heart catheterization. Randomized controlled trials
      comparing the efficacy and safety of different pharmacologic strategies are
      lacking in patients with POPH. The general management includes diuretics and
      oxygen supplementation. Notably, moderate to severe POPH predisposes candidates
      for orthotopic liver transplantation to a higher risk of perioperative mortality.
      Vasomodulating pharmacologic agents are used in patients with moderate to severe
      POPH to decrease pulmonary arterial hypertension, thereby permitting liver
      transplantation to be performed safely. Epo-prostenol is the best-studied
      medication, and bosentan appears promising.

PMID- 19166661
TI  - Hepatic assist devices: will they ever be successful?
AB  - Hepatic assist remains elusive. Bioartificial livers (BALs), consisting of liver
      cells or tissue in a synthetic housing, have been promising but have not proven
      successful in clinical trials. Artificial livers that consist of sophisticated
      sorbents and membranes cannot support a failing liver but may shorten episodes of
      acute decompensation in patients with stable cirrhosis. These artificial livers
      are most likely to find a place as temporary support prior to transplantation.
      True liver support will require a BAL. This article proposes goals for making a
      clinically useful BAL, with attention to systems biology and potential sources of
      hepatocytes.

PMID- 19166662
TI  - Treating hepatocellular carcinoma without liver transplantation.
AB  - Hepatocellular carcinoma, a significant health problem throughout the world,
      generally occurs in the setting of cirrhosis. Choice of treatment depends on the
      size and location of the tumor and hepatic reserve. Liver transplantation
      provides the best chance for long-term survival and can be performed regardless
      of hepatic reserve, but it requires small tumor sizes and is available to only a
      few patients. All other treatments require adequate hepatic reserve. Surgical
      resection, percutaneous ethanol injection, and radiofrequency ablation are
      effective treatments for patients with good hepatic reserve and small tumors
      isolated to the liver. For larger and multinodular tumors, chemoembolization is
      the best choice. With metastasis, portal vein invasion, or large bilobar disease
      and intact hepatic function, modest improvements in survival have occurred with
      the use of sorafenib, a recently approved targeted chemotherapy agent. Patients
      with poor hepatic function or low performance status should receive only
      supportive care.

PMID- 19166663
TI  - The impact of MELD allocation on simultaneous liver-kidney transplantation.
AB  - Model for End-Stage Liver Disease (MELD) allocation has improved the process for
      ranking patients on the liver transplant list. One unintended consequence has
      been an increase in the number of simultaneous liver-kidney (SLK) transplants.
      Some have argued that the system unfairly advantages patients with kidney disease
      and that some kidneys are being prematurely placed in SLK transplantation. This
      review summarizes the MELD score, assessment of kidney function in cirrhosis, the
      impact of kidney function in liver disease, and changes in kidney function status
      in liver transplant recipients in the MELD era. Finally, recommendations
      regarding who should receive SLK transplants are reviewed.

PMID- 19166664
TI  - Caring for adults with pediatric liver disease.
AB  - The etiology of liver disease in childhood varies significantly from its etiology
      in the adult population. More children with complex diseases are surviving into
      adulthood, providing challenges to the primary care provider. Adults with
      pediatric liver disease differ in management, treatment, complications, and
      extrahepatic considerations. To provide these patients with an optimal transition
      into the adult health care system, the provider needs a comprehensive knowledge
      of the common causes of childhood liver disease and their implications and must
      understand the differences in caring for these patients. This review addresses
      some of the most common childhood liver diseases, their causes, presentation,
      evaluation, management, complications, and additional concerns.

PMID- 19166665
TI  - Association between school food environment and practices and body mass index of
      US public school children.
AB  - BACKGROUND: With the ongoing interest in implementing school policies to address
      the problem of childhood obesity, there is a need for information about the
      relationships between school food environments and practices and children's
      weight status. OBJECTIVE: To examine the association between school food
      environments and practices and children's body mass index (BMI; calculated as
      kg/m(2)). DESIGN: The study used data from the third School Nutrition Dietary
      Assessment Study, a cross-sectional study that included a national sample of
      public school districts, schools, and children in the 2004-2005 school year. Data
      on school food environments and practices were collected through on-site
      observations and interviews with school principals, and children were weighed and
      measured by trained data collectors. SUBJECTS/SETTING: The study included 287
      schools and 2,228 children in grades 1 through 12. STATISTICAL ANALYSES
      PERFORMED: Ordinary least squares regression was used to estimate the
      associations between school food environments and practices and BMI z scores and
      logistic regression was used to estimate associations between school food
      environments and practices and the likelihood of obesity (defined as BMI-for-age
      >or=95th percentile). Models included controls for sociodemographic
      characteristics of schools and children, to control for potential endogeneity of
      school environments and practices, as well as controls for children's dietary and
      physical activity behaviors outside of school. RESULTS: Among elementary school
      children, offering french fries and similar potato products in subsidized school
      meals more than once per week and offering dessert more than once per week were
      each associated with a significantly higher likelihood of obesity. Among middle
      school children, the availability of low-nutrient, energy-dense foods in vending
      machines in or near the foodservice area was associated with a higher BMI z
      score, and the availability of such foods for a la carte purchase in the
      cafeteria was associated with a lower BMI z score. CONCLUSIONS: Findings from
      this analysis suggest that limiting children's access to low-nutrient, energy
      dense foods at school may hold promise as a tactic for reducing children's total
      calorie intake and controlling children's BMI.

PMID- 19166666
TI  - School breakfast program but not school lunch program participation is associated
      with lower body mass index.
AB  - BACKGROUND: Rates of overweight and obesity have increased dramatically during
      the past 2 decades. Children obtain a large fraction of their food energy while
      at school. OBJECTIVE: To estimate the relationship between participation in
      school meal programs and children's body mass index (BMI) and their likelihood of
      being overweight or obese, testing the hypothesis that school meal participation
      influences students' weight status, as measured by their BMI and indicators of
      overweight and obesity. DESIGN: A cross-sectional design in which a regression
      model was used to estimate the association between participation in the School
      Breakfast Program and National School Lunch Program and children's BMI and risk
      of overweight or obesity, controlling for a wide range of student and school
      characteristics. SUBJECTS/SETTING: Participants included a nationally
      representative sample from the third School Nutrition Dietary Assessment Study of
      2,228 students in grades 1 through 12 for whom height and weight measurements
      were obtained. These students, along with their parents, each completed a survey.
      STATISTICAL ANALYSES PERFORMED: Multivariate regression models were used to
      examine the relationship between usual school meal participation and BMI and
      indicators of whether students were overweight or obese. These models controlled
      for students' demographic and socioeconomic characteristics, levels of physical
      activity, usual eating habits, screen time, and school characteristics. RESULTS:
      No evidence was found of any relationship between usual school lunch
      participation and any of four different measures of weight status based on
      students' BMI. School breakfast participation was associated with significantly
      lower BMI, particularly among non-Hispanic, white students. CONCLUSIONS: There
      was no evidence that either the school breakfast or lunch program is contributing
      to rising rates of childhood obesity. In fact, School Breakfast Program
      participation may be a protective factor, by encouraging students to consume
      breakfast more regularly.

PMID- 19166667
TI  - The third School Nutrition Dietary Assessment Study: summary and implications.

PMID- 19166668
TI  - A practice perspective on the third School Nutrition Dietary Assessment Study.

PMID- 19166669
TI  - Evaluation's vital role in healthier school meals.

PMID- 19166670
TI  - The third School Nutrition Dietary Assessment Study: background and study design.
AB  - OBJECTIVE: This article describes the background and design of the third School
      Nutrition Dietary Assessment Study (SNDA-III). DESIGN: SNDA-III is a nationally
      representative cross-sectional study of the National School Lunch Program and the
      School Breakfast Program in 2005. The three-stage sample design allowed
      description of district and school food environments and policies, analysis of
      foods and nutrients in school lunches and breakfasts, and assessment of the role
      of school meals and competitive foods in students' diets. Surveys of district and
      school staff were by telephone or in person; school menu data were collected in a
      mail survey with telephone assistance; and student and parent interviews were
      conducted in person and in school, except that parents of secondary-school
      students were interviewed by telephone. Student interviews included a 24-hour
      dietary recall, as well as measurement of height and weight. Response rates were
      83% for districts, 95% for schools, and 63% for students, whose participation was
      constrained by consent issues and school schedules. SUBJECTS/SETTING: Data were
      collected from 130 public school food authorities (districts that offer federally
      subsidized school meals), 398 schools within those districts, and 2,314 public
      school students in grades 1 through 12 in these schools. Of the 2,314 students, a
      random subset of 666 (29%) completed a second recall to permit estimation of
      usual nutrient intake distributions. STATISTICAL ANALYSES PERFORMED: Descriptive
      tabulations were used to summarize the background characteristics of schools and
      students and most study outcomes. Multivariate regression models and propensity
      score matching were used to compare the nutrient intakes of school meal
      participants and nonparticipants. CONCLUSIONS: SNDA-III data provide a rich
      resource for examining interactions among the school meal programs, the school
      food environment, students' diets, and child obesity. Subsequent articles in this
      Supplement present analyses in all these areas.

PMID- 19166671
TI  - Meals offered and served in US public schools: do they meet nutrient standards?
AB  - BACKGROUND: Concerns about the diets of school-aged children and new nutrition
      recommendations for the US population have increased interest in the nutritional
      quality of meals available through the National School Lunch Program and School
      Breakfast Program. OBJECTIVE: This article updates national estimates of the food
      energy and nutrient content of school meals and compares these estimates to
      federal nutrient standards established under the 1995 School Meals Initiative for
      Healthy Children. DESIGN: Data were collected as part of the third School
      Nutrition Dietary Assessment Study, a nationally representative cross-sectional
      study fielded during school year 2004-2005. Menu and recipe data for a typical
      school week were collected in a mail survey with telephone assistance. Nutrient
      information for common commercially prepared food items was obtained from
      manufacturers, to supplement the Food and Nutrient Database for Dietary Studies
      used to analyze the data. Analyses were conducted for meals offered and meals
      served to (selected by) children. SUBJECTS/SETTING: Samples of 130 public school
      districts that offered federally subsidized school meals, and 398 schools within
      those districts, participated in the study. Foodservice managers in each school
      completed a menu survey. STATISTICAL ANALYSES PERFORMED: Descriptive tabulations
      present weighted means, proportions, and standard errors for elementary, middle,
      and high schools, and for all schools combined. RESULTS: Most schools offered and
      served meals that met the standards for protein, vitamins, and minerals. Fewer
      than one third of schools met the standards for energy from fat or saturated fat
      in the average lunch, whereas three fourths or more met the fat standards in
      school breakfasts. For both meals, average levels of sodium were high and fiber
      was low relative to Dietary Guidelines for Americans 2005 recommendations.
      CONCLUSIONS: For school meals to meet nutrient standards and promote eating
      behaviors consistent with the Dietary Guidelines, future policy, practice, and
      research should focus on reducing levels of fat and sodium and increasing fiber.

PMID- 19166672
TI  - Nutritional quality of the diets of US public school children and the role of the
      school meal programs.
AB  - BACKGROUND: Good nutrition is essential to healthy childhood. Because the school
      meal programs--the National School Lunch Program and the School Breakfast Program
      -are so widely available, they are in a unique position to influence the
      nutritional quality of children's diets. OBJECTIVE: This article assesses the
      nutritional quality of the diets of US public school children and explores the
      relationship between children's participation in the school meal programs and the
      nutritional quality of their diets. DESIGN: Data were collected as part of the
      third School Nutrition Dietary Assessment Study (SNDA-III), a nationally
      representative study fielded during school year 2004-2005. Data on children's
      dietary intakes were collected through in-person 24-hour dietary recalls.
      Nutritional quality of children's diets was assessed by estimating the prevalence
      of inadequate and excessive intakes of energy and nutrients. SUBJECTS/SETTING:
      The analysis is based on a nationally representative sample of 2,314 children in
      grades 1 through 12 from 287 public schools. STATISTICAL ANALYSES PERFORMED:
      Nutrient adequacy and excess were assessed by comparing usual nutrient intake
      distributions to Dietary Reference Intakes and the Dietary Guidelines for
      Americans 2005. Propensity score matching was used to examine the relationship
      between school meal program participation and the prevalence of inadequate and
      excessive intakes. RESULTS: The majority of public school children in the United
      States had nutritionally adequate diets, but 80% had excessive intakes of
      saturated fat and 92% had excessive intakes of sodium. School meal program
      participation was associated with reduced prevalence of nutrient inadequacy but
      with increased prevalence of excessive sodium intakes. CONCLUSIONS: School meal
      programs play an important role in the nutritional adequacy of children's diets.
      However, the association between program participation and excessive sodium
      intakes, along with the high prevalence of excessive saturated fat intakes among
      all students, suggest areas for improvement in the meals these programs provide.

PMID- 19166673
TI  - Availability and consumption of competitive foods in US public schools.
AB  - BACKGROUND: With ongoing efforts to develop and implement school wellness
      policies, there is a need for information about the availability and consumption
      of competitive foods in schools. OBJECTIVE: To describe the availability of
      competitive foods in US public schools, consumption of competitive foods by
      children, and contributions of competitive foods to energy intakes. DESIGN: The
      study used data from the third School Nutrition Dietary Assessment Study, a cross
      sectional study that included a national sample of public school districts,
      schools, and children in the 2004-2005 school year. On-site observations were
      used to document the availability of competitive foods and a 24-hour recall was
      used to assess children's consumption of competitive foods. SUBJECTS/SETTING: The
      study included 287 schools and 2,314 children in grades 1 through 12. STATISTICAL
      ANALYSES PERFORMED: Most analyses were limited to estimation of means and
      proportions. Two-tailed t tests were used to test the significance of differences
      between children who did and did not eat a school lunch. RESULTS: In school year
      2004-2005, competitive foods were widely available in public schools. Overall,
      40% of children consumed one or more competitive foods on a typical school day.
      The most commonly consumed competitive foods were foods and beverages that were
      low in nutrients and energy-dense. Children who ate a school lunch were
      significantly less likely than children who did not eat a school lunch to consume
      competitive foods (36% vs 45%; P<0.01); however, the leading competitive food
      choices for both groups of children were foods that were low in nutrients and
      energy-dense. On average, competitive food consumers who ate school lunches
      obtained 159 calories from competitive foods that were low in nutrients and
      energy-dense, compared with 201 calories for competitive food consumers who did
      not eat school lunches (P<0.05). CONCLUSIONS: In school year 2004-2005,
      competitive foods were widely available and consumed in US public schools and the
      most commonly consumed competitive foods were low in nutrients and energy-dense.
      These data support the need for improvements in school food environments and
      policies and provide a useful baseline for monitoring change as schools work to
      make these improvements.

PMID- 19166674
TI  - School meals: types of foods offered to and consumed by children at lunch and
      breakfast.
AB  - BACKGROUND: Children's food intakes do not meet dietary recommendations. Meals
      offered through the National School Lunch Program and School Breakfast Program
      make substantial contributions to school-aged children's diets. OBJECTIVES: This
      article describes foods offered in school meals and consumed by children at lunch
      and breakfast, and differences in foods consumed by children who did and did not
      participate in the school meal programs. DESIGN: Data were collected as part of
      the third School Nutrition Dietary Assessment Study, a cross-sectional,
      nationally representative study conducted in 2005. School menu surveys were used
      to identify the foods offered in school meals, and 24-hour dietary recalls were
      used to assess the foods children consumed. SUBJECTS/SETTING: Foodservice
      managers in 398 public schools and 2,314 children (grades 1 to 12) from 287 of
      these schools participated in the study. STATISTICAL ANALYSES PERFORMED:
      Descriptive tabulations report percentages of daily menus that offered and
      percentages of children that consumed specific food groups and foods at lunch and
      breakfast. Two-tailed t tests were used to assess differences between school meal
      program participants and nonparticipants. RESULTS: Most school menus offered
      nonfat or 1% milk, fruit or 100% juice, and vegetables daily. Starchy vegetables
      were more common than dark green/orange vegetables or legumes. School lunch
      participants were significantly more likely than nonparticipants to consume milk,
      fruit, and vegetables, and significantly less likely to consume desserts, snack
      items, and beverages other than milk or 100% juice. At breakfast, participants
      were significantly more likely than nonparticipants to consume milk and fruit
      (mainly 100% juice), and significantly less likely to consume beverages other
      than milk or 100% juice. CONCLUSIONS: Consumption of school meals is positively
      related to children's intakes of key food groups at lunch and breakfast. Offering
      more fresh fruit, whole grains, and a greater variety of vegetables could lead to
      additional health benefits.

PMID- 19166675
TI  - The third School Nutrition Dietary Assessment Study: findings and policy
      implications for improving the health of US children.

PMID- 19166676
TI  - Consumption of low-nutrient, energy-dense foods and beverages at school, home,
      and other locations among school lunch participants and nonparticipants.
AB  - BACKGROUND: Access to foods and beverages on school campuses, at home, and other
      locations affects children's diet quality, energy intake, and risk of obesity.
      OBJECTIVES: To describe patterns of consumption of "empty calories"--low
      nutrient, energy-dense foods, including sugar-sweetened beverages--by eating
      location among National School Lunch Program (NSLP) participants and
      nonparticipants. DESIGN: Cross-sectional study using 24-hour dietary recall data
      from the 2004-2005 third School Nutrition Dietary Assessment Study.
      SUBJECTS/SETTING: A nationally representative sample of 2,314 children in grades
      one through 12, including 1,386 NSLP participants. STATISTICAL ANALYSES
      PERFORMED: Comparisons, using t tests, of the proportion of children consuming
      low-nutrient, energy-dense foods and beverages, mean daily energy and energy from
      low-nutrient, energy-dense foods, and energy density by NSLP participation
      status. RESULTS: On a typical school day, children consumed 527 "empty calories"
      during a 24-hour period. Eating at home provided the highest mean amount of
      energy from low-nutrient, energy-dense foods (276 kcal vs 174 kcal at school and
      78 kcal at other locations). NSLP participants consumed less energy from sugar
      sweetened beverages at school than nonparticipants (11 kcal vs 39 kcal in
      elementary schools and 45 kcal vs 61 kcal in secondary schools, P<0.01), but more
      energy from low-nutrient, energy-dense solid foods such as french fries and
      higher-fat baked goods in secondary schools (157 kcal vs 127 kcal, P<0.01).
      Participants were not more likely to consume sugar-sweetened beverages or low
      nutrient, energy-dense foods at home or other locations. School lunch
      participants' consumption at school was less energy-dense than nonparticipants'
      consumption at school (P<0.01). Energy density was highest for consumption at
      locations away from home and school. CONCLUSIONS: Improving home eating
      behaviors, where the largest proportion of total daily and energy from low
      nutrient, energy-dense foods are consumed (especially from sugar-sweetened
      beverages, chips, and baked goods) is warranted. At schools, consumption of
      energy from low-nutrient, energy-dense foods may be reduced by limiting access to
      competitive foods and beverages, enforcing strong school wellness policies, and
      minimizing the frequency of offering french fries and similar potato products and
      higher-fat baked goods in school meals or a la carte.

PMID- 19166677
TI  - School food environments and practices affect dietary behaviors of US public
      school children.
AB  - BACKGROUND: Changes to school food environments and practices that lead to
      improved dietary behavior are a powerful strategy to reverse the childhood
      obesity epidemic. OBJECTIVES: To estimate the effects of school food environments
      and practices, characterized by access to competitive foods and beverages, school
      lunches, and nutrition promotion, on children's consumption of sugar-sweetened
      beverages, low-nutrient energy-dense foods, and fruits/vegetables at school.
      DESIGN: Cross-sectional study using data from the third School Nutrition Dietary
      Assessment Study, a nationally representative sample of public school districts,
      schools, and children in school year 2004-2005. Data from school principals and
      foodservice directors, school menu analysis, and on-site observations were used
      to characterize school food environments and practices. Dietary intake was
      assessed using 24-hour recalls. SUBJECTS/SETTING: The sample consists of 287
      schools and 2,314 children in grades one through 12. STATISTICAL ANALYSES
      PERFORMED: Ordinary least squares regression was used to identify the association
      between school food environments and practices (within elementary, middle, and
      high schools) and dietary outcomes, controlling for other school and child/family
      characteristics. RESULTS: Sugar-sweetened beverages obtained at school
      contributed a daily mean of 29 kcal in middle school children and 46 kcal in high
      school children across all school children. Attending a school without stores or
      snack bars was estimated to reduce sugar-sweetened beverage consumption by 22
      kcal per school day in middle school children (P<0.01) and by 28 kcal in high
      school children (P<0.01). The lack of a pouring rights contract in a school
      reduced sugar-sweetened beverage consumption by 16 kcal (P<0.05), and no a la
      carte offerings in a school reduced consumption by 52 kcal (P<0.001) in middle
      school children. The most effective practices for reducing energy from low
      energy, energy-dense foods were characteristics of the school meal program; not
      offering french fries reduced low-nutrient, energy-dense foods consumption by 43
      kcal in elementary school children (P<0.01) and sugar-sweetened beverage
      consumption by 41 kcal in high school children (P<0.001). CONCLUSIONS: To improve
      children's diet and reduce obesity continued changes to school food environments
      and practices are essential. Removing sugar-sweetened beverages from school food
      stores and snack bars, improving a la carte choices, and reducing the frequency
      of offering french fries merit testing as strategies to reduce energy from low
      nutrient, energy-dense foods at school.

PMID- 19166678
TI  - Current use of beta blockers in patients with reactive airway disease who are
      hospitalized with acute coronary syndromes.
AB  - Beta blockers have a proven benefit in the management of patients with acute
      coronary syndromes (ACS) and for secondary prevention of coronary events. Current
      guidelines list such reactive airway diseases (RADs) such as asthma and chronic
      obstructive pulmonary disease as relative contraindications to beta-blocker use.
      However, the co-morbid burden of RAD and coronary heart disease is substantial,
      and data suggest that the treatment benefit of beta blockers is shared by
      patients with RAD. The Get with the Guidelines (GWTG) database was used to
      evaluate use of beta blockers within 24 hours of admission and at discharge in
      patients with ACS with (n = 12,967) and without (n = 81,140) a history of RAD.
      Data were collected in 435 hospitals between January 2000 and September 2006. A
      multivariable logistic regression model was used to determine predictors of beta
      blocker treatment. In patients with no RAD history, beta-blocker prescription
      rates were 78.3% at admission and 88.7% at discharge; in patients with a RAD
      history, rates were 65.6% at admission and 77.2% at discharge. Compared with
      patients with no history of RAD, patients with a history of RAD were 42% less
      likely (odds ratio 0.58, confidence interval 0.54 to 0.62, p <0.0001) to receive
      a beta blocker upon admission and 55% less likely (odds ratio 0.45, confidence
      interval 0.41 to 0.48, p <0.0001) to receive a beta blocker at discharge in
      multivariable analysis. Among all other clinical factors, RAD history was the
      most significant predictor of likelihood of not receiving a beta blocker at
      admission or discharge. Receipt of beta blockers within 24 hours after admission
      was associated with a lower in-hospital mortality rate for patients with RAD
      (odds ratio = 0.52, p <0.001) and for patients without RAD (odds ratio = 0.38, p
      <0.001). Careful assessment of beta-blocker safety and RAD severity by physicians
      is needed to improve beta-blocker prescription rates in this large group of
      patients with ACS.

PMID- 19166679
TI  - Differentiating ST elevation myocardial infarction and nonischemic causes of ST
      elevation by analyzing the presenting electrocardiogram.
AB  - Guidelines recommend that patients with suggestive symptoms of myocardial
      ischemia and ST-segment elevation (STE) in > or =2 adjacent electrocardiographic
      leads should receive immediate reperfusion therapy. Novel strategies aimed to
      reduce door-to-balloon time, such as prehospital wireless electrocardiographic
      transmission, may be dependent on the interpretation accuracy of the
      electrocardiogram (ECG) readers. We assessed the ability of experienced
      electrocardiographers to differentiate among STE, acute STE myocardial infarction
      (STEMI), and nonischemic STE (NISTE). A total of 116 consecutive ECGs showing STE
      were studied. Fifteen experienced cardiologists were asked to decide, based on
      the ECG and assuming that the patient had compatible symptoms, whether they would
      send each patient for primary percutaneous coronary intervention (PPCI). If NISTE
      was chosen, the reader selected 1 or more 12 possible options to explain the
      choice. Of 116 patients, only 8 had STEMI. The percentage of ECGs for which PPCI
      was recommended for the patient by the individual readers varied widely (7.8% to
      33%). There was no significant difference between the North American and Other
      Countries readers (p = 0.13). The sensitivity and specificity of the individual
      readers ranged from 50% to 100% (average 75%) and 73% to 97% (average 85%),
      respectively. There were broad inconsistencies among the readers in the chosen
      reasons used to classify NISTE. In conclusion, we found wide variations among
      experienced electrocardiographers in reading ECGs with STE and differentiating
      STEMI with need for PPCI from NISTE. There is a need to revise our current
      electrocardiographic criteria for differentiating STEMI from NISTE.

PMID- 19166680
TI  - Relation of death within 90 days of non-ST-elevation acute coronary syndromes to
      variability in electrocardiographic morphology.
AB  - Electrocardiographic measures can facilitate the identification of patients at
      risk of death after acute coronary syndromes. This study evaluates a new risk
      metric, morphologic variability (MV), which measures beat-to-beat variability in
      the shape of the entire heart beat signal. This metric is analogous to heart rate
      variability (HRV) approaches, which focus on beat-to-beat changes in the heart
      rate. MV was calculated using a dynamic time-warping technique in 764 patients
      from the DISPERSE2 (TIMI 33) trial for whom 24-hour continuous electrocardiograph
      was recorded within 48 hours of non-ST-elevation acute coronary syndrome. The
      patients were evaluated during a 90-day follow-up for the end point of death.
      Patients with high MV showed an increased risk of death during follow-up (hazard
      ratio 8.46; p <0.001). The relationship between high MV and death could be
      observed even after adjusting for baseline clinical characteristics and HRV
      measures (adjusted hazard ratio 6.91; p = 0.001). Moreover, the correlation
      between MV and HRV was low (R < or =0.25). These findings were consistent among
      several subgroups, including patients under the age of 65 and those with no
      history of diabetes or hyperlipidemia. In conclusion, our results suggest that
      increased variation in the entire heart beat morphology is associated with a
      considerably elevated risk of death and may provide information complementary to
      the analysis of heart rate.

PMID- 19166681
TI  - Frequency of electrocardiographic recordings in patients presenting with angina
      pectoris (from the Investigation of National Coronary Disease Identification).
AB  - The appropriate progression of diagnostic testing for acute angina has been the
      topic of several recommendations by the American College of Cardiology and
      American Heart Association (ACC/AHA). We measured how frequently
      electrocardiography (ECG) is provided as the initial cardiac diagnostic test, as
      recommended for patients with new angina. Using an insurance database
      representing 2% of the U.S. adult population, we identified patients undergoing a
      new cardiac diagnostic process for angina. Rates of initial ECG were stratified
      by age, gender, co-morbid disease, and care setting. Of 4.4 million patients,
      18,139 met the entry criteria by presenting with anginal symptoms for testing. A
      substantial portion (35%, 95% confidence interval [CI] 34% to 35%) did not
      receive the initial ECG recommended by expert guidelines. Patients treated in
      emergency departments received an initial ECG more frequently (91%, CI 90% to
      92%) than patients tested in outpatient settings (61%, CI 60% to 62%; risk ratio
      [RR] 0.67, CI for RR 0.65 to 0.68) or in inpatient hospital settings (34%, CI 32%
      to 37%; RR 0.38, CI for RR 0.36 to 0.40). Slightly lower rates of initial ECG
      were observed in men (RR 0.93 vs women, CI for RR 0.91 to 0.95) and patients over
      64 years (RR 0.93 vs younger patients, CI for RR 0.91 to 0.95). Total diagnostic
      costs averaged $954 when testing began with the recommended ECG versus $1,233
      when testing did not. In conclusion, ECG is not universally obtained as the
      initial test for patients presenting with anginal symptoms despite evidence-based
      recommendations for such use. Clinicians should be aware that suboptimal use of
      ECG in certain settings may hinder investigations of heart disease.

PMID- 19166682
TI  - Comparison of outcomes and safety of "facilitated" versus primary percutaneous
      coronary intervention in patients with ST-segment elevation myocardial
      infarction.
AB  - Recent studies have documented that use of "facilitated" percutaneous coronary
      intervention (PCI) in patients with ST-segment elevation myocardial infarction
      (STEMI) may be harmful. In-hospital outcomes in 1,553 consecutive patients with
      STEMI without cardiogenic shock who underwent PCI at a single tertiary center
      within 6 hours of presentation were analyzed. The study group included 767
      patients who underwent primary PCI who initially presented to the tertiary center
      and were triaged for emergent PCI and 786 patients who underwent facilitated PCI
      who were pretreated at a community hospital with a glycoprotein IIb/IIIa platelet
      inhibitor and/or intravenous thrombolytic therapy before transfer for catheter
      based therapy. Compared with patients who underwent primary PCI, the facilitated
      PCI group had longer door-to-balloon times (162 +/- 57 vs 113 +/- 61 minutes),
      higher baseline infarct-vessel TIMI 3 flow rates (52.8% vs 25.4%; p <0.001), and
      no increase in major adverse in-hospital outcomes. In patients treated with door
      to-balloon times >90 and < or =150 minutes, patients who underwent facilitated
      PCI had fewer composite major adverse clinical events (combined mortality,
      recurrent myocardial infarction, emergent repeated PCI, hemorrhagic and
      nonhemorrhagic stroke, and nonintracranial TIMI major bleeding) compared with
      patients who underwent primary PCI (relative risk 0.50, 95% confidence interval
      0.26 to 0.96, p = 0.034). In conclusion, facilitated PCI can be safely used to
      increase pharmacologic reperfusion before catheter-based therapy in patients with
      STEMI without an increase in clinical hazard and with fewer major adverse
      clinical events in patients treated with door-to-balloon times >90 and < or =150
      minutes.

PMID- 19166683
TI  - Combined prognostic utility of white blood cell count, plasma glucose, and
      glomerular filtration rate in patients undergoing primary stent placement for
      acute myocardial infarction.
AB  - Although high white blood cell (WBC) count and plasma glucose (PG) and low
      glomerular filtration rate (GFR) on admission have been associated with poor
      outcomes after acute myocardial infarction (AMI), the combined prognostic utility
      of these 3 variables was unclear. The association of WBC count, PG, and GFR on
      admission to in-hospital outcomes was examined in 2,633 patients who underwent
      primary stent placement for ST-segment elevation AMI within 48 hours after
      symptom onset. In-hospital mortality progressively increased as the number of the
      variables of high WBC count (> or =11,120/microl; upper tertile), high PG (> or
      =10.4 mmol/L; upper tertile), and low GFR (< or =60 ml/min/1.73 m(2); lower
      tertile) increased. Patients with all 3 variables had a strikingly higher in
      hospital mortality rate (25.9%). After adjusting for baseline characteristics,
      multivariate analysis showed that compared with patients who had none of these
      variables, odds ratios for in-hospital mortality were 1.63 (95% confidence
      interval [CI] 0.88 to 3.03, p = 0.12) in patients with only 1 variable, 2.33 (95%
      CI 1.28 to 3.96, p = 0.047) in those with 2 variables, and 6.16 (95% CI 2.98 to
      12.6, p <0.001) in those with all 3 variables. In conclusion, combined evaluation
      of WBC count, PG, and GFR on admission was a simple and useful method for the
      early prediction of risk of in-hospital death in patients undergoing primary
      stent placement for ST-segment elevation AMI.

PMID- 19166684
TI  - Hematologic parameters, atherosclerotic progression, and prognosis in patients
      with previous coronary artery bypass grafting (from the Post CABG Trial).
AB  - Although inflammatory markers and anemia have both been associated with prognosis
      in patients with cardiovascular disease, their relation with atherosclerotic
      progression in patients with previous coronary artery bypass grafting (CABG) is
      unknown. A total of 1,273 patients enrolled in the Post CABG Trial who had
      undergone CABG 1 to 11 years before entry were studied. Subjects were randomly
      assigned to lovastatin in low or high doses and low-dose warfarin or placebo in a
      factorial design. Subjects underwent coronary angiography at baseline and after a
      mean follow-up of 4.3 years. White blood cells (WBCs), hemoglobin, and platelets
      were measured at baseline in all subjects. Graft progression was defined as a
      decrease > or =0.6 mm in lumen diameter at the site of greatest change at follow
      up. During follow-up, 195 subjects sustained a clinical event and 857 grafts
      developed significant worsening. Risk of clinical events tended to be greater
      with higher WBC counts, with hazard ratios for ascending quartiles of 1.4 (95%
      confidence interval [CI] 0.9 to 2.2), 1.6 (95% CI 1.0 to 2.6), and 1.6 (95% CI
      1.0 to 2.7). WBC count also tended to be associated with significant
      atherosclerotic progression, particularly in subjects assigned to placebo rather
      than warfarin (p interaction = 0.04). There was no association of hemoglobin or
      platelet count with risk of clinical events or graft progression, but few trial
      subjects were anemic. In conclusion, WBC count is associated with a graded
      increase in cardiovascular events in patients with coronary artery bypass grafts.

PMID- 19166685
TI  - Association of leukocyte and neutrophil counts with infarct size, left
      ventricular function and outcomes after percutaneous coronary intervention for ST
      elevation myocardial infarction.
AB  - Elevated leukocyte count during ST-segment elevation myocardial infarction is
      associated with adverse clinical outcomes. Whether increased leukocyte count
      after primary percutaneous coronary intervention (PCI) directly reflects larger
      infarct size and left ventricular impairment is not known. The aim of this study
      was to assess the relation between leukocyte and neutrophil counts with infarct
      size and the left ventricular ejection fraction (LVEF) after primary PCI. Three
      hundred sixty-three patients from the Evaluation of MCC-135 for Left Ventricular
      Salvage in Acute Myocardial Infarction (EVOLVE) study, a randomized, double
      blind, placebo-controlled trial assessing the efficacy of intracellular calcium
      modulator as an adjunct to primary PCI in patients with first ST-segment
      elevation myocardial infarctions, were evaluated. Total and differential
      leukocyte counts were measured before and serially after PCI. Infarct size and
      the LVEF were assessed using single-photon emission computed tomography after 5
      and 30 days, and patients were followed up to 180 days. Total leukocyte and
      neutrophil counts obtained 24 hours after PCI were significantly correlated with
      infarct size (r = 0.34 and 0.37, respectively, p <0.001) and inversely correlated
      with the LVEF (r = -0.20 and -0.22, respectively, p <0.001). Patients with
      elevated leukocyte and neutrophil counts had larger infarct sizes (12.5% vs 5%
      and 13.5% vs 5%, respectively, p <0.001). The highest neutrophil quartile was
      associated with increased 180-day composite cardiac events (19% vs 20% vs 23% vs
      45%, log-rank p <0.001). Elevated leukocyte and neutrophil counts independently
      predicted adverse cardiac events (hazard ratios 2.5 and 2.2, respectively, p =
      0.001). In conclusion, elevated leukocyte and neutrophil counts after primary PCI
      in patients with ST-segment elevation myocardial infarctions are directly related
      to myocardial infarct size and the LVEF and are independent predictors of
      cardiovascular outcomes.

PMID- 19166686
TI  - Cost-effectiveness of drug-eluting stents including the economic impact of late
      stent thrombosis.
AB  - Recent studies examining the effectiveness of drug-eluting stents (DES) have
      found that the use of DES is associated with a significant increase in the
      incidence of late stent thrombosis (LST). Previous cost-effectiveness analyses of
      DES have not accounted for the costs associated with LST. In this study,
      published research was reviewed to identify studies that compared the cost
      effectiveness of DES with that of bare-metal stents and to identify the incidence
      of LST. Probable costs were assigned to LST-related myocardial infarction and
      death on the basis of the treatment costs for these outcomes. These costs as well
      as those of extended clopidogrel therapy were then incorporated into the
      Sirolimus-Eluting Balloon Expandable Stent in the Treatment of Patients With De
      Novo Native Coronary Artery Lesions (SIRIUS) and TAXUS-IV cost-effectiveness
      data. This review found that the incidence of LST ranged from 0.2% to 0.7%.
      Assuming a base case LST incidence of 0.5%, a cost per death of $20,000, a cost
      per myocardial infarction of $20,000, and a cost of an additional 2 years of
      clopidogrel therapy of $2,428 per patient, the costs per revascularization
      avoided were $15,056 for the SIRIUS trial and $25,210 for the TAXUS-IV trial. The
      costs per quality-adjusted life-year gained were $250,935 and $257,591,
      respectively. Sensitivity analyses revealed that the costs per revascularization
      avoided varied from $14,618 to $15,830 for the SIRIUS trial and from $24,540 to
      $26,396 for the TAXUS-IV trial. Similarly, the cost per quality-adjusted life
      year gained varied from $243,638 to $263,840 for the SIRIUS trial and from
      $250,739 to $269,708 for the TAXUS-IV trial. In conclusion, LST-related adverse
      events and the need for extended clopidogrel therapy substantially increase the
      costs associated with the implementation of DES. The inclusion of these costs
      renders the widespread use of DES not cost effective in the United States in
      terms of cost per quality-adjusted life-year gained and cost per
      revascularization avoided.

PMID- 19166687
TI  - Comparison of the sirolimus-eluting versus paclitaxel-eluting coronary stent in
      patients with diabetes mellitus: the diabetes and drug-eluting stent (DiabeDES)
      randomized angiography trial.
AB  - The aim of the present study was to evaluate angiographic late luminal loss after
      the implantation of sirolimus-eluting Cypher stents and paclitaxel-eluting Taxus
      stents in patients with diabetes. The study was a Danish multicenter, open-label,
      randomized trial. One hundred fifty-three patients with diabetes with coronary
      artery disease were randomized to Cypher (n = 76) or Taxus (n = 77) stent
      implantation. All patients were followed for 8 months. The primary end point was
      8-month angiographic in-stent late luminal loss. This primary end point was
      reduced in the Cypher group compared with the Taxus group (0.23 +/- 0.54 vs 0.44
      +/- 0.52 mm, p = 0.025). Angiographic in-segment restenosis at 8-month follow-up,
      a secondary end point, was present in 16 patients (Cypher, n = 6; Taxus, n = 10;
      p = 0.24). Target lesion revascularization was performed in 5 patients (6.5%) and
      9 patients (11.8%) in the Cypher and Taxus groups, respectively (p = 0.25).
      Definite stent thrombosis was observed in 2 patients (in the Taxus group), no
      patients had probable stent thrombosis, and 1 patient in each group had possible
      stent thrombosis. Major adverse cardiac events (cardiac death, myocardial
      infarction, definite stent thrombosis, or target lesion revascularization) were
      observed in 17 patients (Cypher, n = 6; Taxus, n = 11; p = 0.19). In conclusion,
      angiographic in-stent late luminal loss is significantly reduced in patients with
      diabetes by use of the sirolimus-eluting Cypher stent compared with the
      paclitaxel-eluting Taxus stent.

PMID- 19166688
TI  - Relation of high-density lipoprotein cholesterol to mortality after percutaneous
      coronary interventions in patients with low-density lipoprotein <70 mg/dl.
AB  - High-density lipoprotein (HDL) cholesterol level is a strong predictor of
      morbidity and mortality in the general population. Conflicting data exist on the
      protective effects of high HDL cholesterol in patients with optimal low-density
      lipoprotein (LDL) cholesterol levels. To determine the association of high HDL
      cholesterol with mortality in patients with LDL cholesterol levels <70 mg/dl who
      undergo percutaneous coronary intervention, 3,616 consecutive patients with LDL
      cholesterol levels <70 mg/dl who underwent percutaneous coronary intervention
      from July 1, 1999, to June 1, 2007, were retrospectively analyzed and followed
      through July 1, 2007. All-cause mortality was identified using the National Death
      Index. The mortality rates was 34.7, 25.2, 23.7, and 18.8 per 1,000 person-years
      in patients with HDL cholesterol levels of <40, 40 to 49, 50 to 59, and > or =60
      mg/dl, respectively (p for trend <0.001). After multivariate adjustment for
      demographic characteristics, cigarette smoking, biochemical variables, and co
      morbid conditions, the hazard ratios for mortality in patients with HDL
      cholesterol levels of 40 to 49, 50 to 59, and > or =60 mg/dl, compared with their
      counterparts with HDL cholesterol levels <40 mg/dl, were 0.68 (95% confidence
      interval [CI] 0.50 to 0.93), 0.55 (95% CI 0.35 to 0.85), and 0.45 (95% CI 0.27 to
      0.74), respectively. For each 1-SD increase in HDL cholesterol level (14 mg/dl),
      the multivariate-adjusted hazard ratio for all-cause mortality was 0.68 (95% CI
      0.58 to 0.79). In conclusion, in patients with LDL cholesterol levels <70 mg/dl
      who underwent percutaneous coronary intervention, a strong inverse association
      was present between HDL cholesterol level and all-cause mortality.

PMID- 19166689
TI  - Impact of left ventricular dysfunction on hospital mortality among patients
      undergoing elective percutaneous coronary intervention.
AB  - Many patients with systolic dysfunction undergo elective percutaneous coronary
      intervention (PCI) despite the unknown risk and limited data supporting its use.
      Therefore, the aim of this study was to evaluate the association between the
      severity of left ventricular (LV) systolic dysfunction and hospital mortality in
      patients who undergo elective PCI. A retrospective cohort study was conducted of
      all patients who underwent elective PCI in New York State in 1998 and 1999.
      Patients were stratified into 5 groups on the basis of their LV ejection
      fractions (EFs) before PCI (>55%, 46% to 55%, 36% to 45%, 26% to 35%, and < or
      =25%). Comparisons of demographic, procedural, and outcome variables were
      performed, and adjusted odds ratios (ORs) were calculated to evaluate the
      relation between the EF and hospital mortality. Among 55,709 patients who
      underwent elective PCI, EFs < or =25%, 26% to 35% and 36% to 45% were present in
      3.4%, 7.6%, and 17.4%, respectively. Hospital mortality was 0.3%, 0.2%, 0.6%,
      1.2%, and 2.7% in the groups with EFs >55%, 46% to 55%, 36% to 45%, 26% to 35%,
      and < or =25%, respectively (p <0.001). After multivariate adjustment, an
      increased risk for hospital mortality was significant for EF groups of 36% to 45%
      (OR 1.56, 95% confidence interval 1.06 to 2.30), 26% to 35% (OR 2.17, 95%
      confidence interval 1.42 to 3.31), and < or =25% (OR 3.85, 95% confidence
      interval 2.46 to 6.01) compared with EF >55%, respectively. In conclusion, this
      analysis demonstrates that elective PCI is commonly performed in patients with
      reduced EFs, and the risk for hospital mortality increases as the EF decreases.
      For patients who undergo elective PCI, an EF < or =45% is associated with higher
      adjusted hospital mortality. Whether elective PCI in patients with low EFs
      reduces morbidity and/or mortality over medical therapy alone is unknown.

PMID- 19166690
TI  - Alcohol drinking and cardiovascular risk in a population with high mean alcohol
      consumption.
AB  - Moderate alcohol consumption has been associated with lower coronary artery
      disease (CAD) risk. However, data on the CAD risk associated with high alcohol
      consumption are conflicting. The aim of this study was to examine the impact of
      heavier drinking on 10-year CAD risk in a population with high mean alcohol
      consumption. In a population-based study of 5,769 adults (aged 35 to 75 years)
      without cardiovascular disease in Switzerland, 1-week alcohol consumption was
      categorized as 0, 1 to 6, 7 to 13, 14 to 20, 21 to 27, 28 to 34, and > or =35
      drinks/week or as nondrinkers (0 drinks/week), moderate (1 to 13 drinks/week),
      high (14 to 34 drinks/week), and very high (> or =35 drinks/week). Blood pressure
      and lipids were measured, and 10-year CAD risk was calculated according to the
      Framingham risk score. Seventy-three percent (n = 4,214) of the participants
      consumed alcohol; 16% (n = 909) were high drinkers and 2% (n = 119) very high
      drinkers. In multivariate analysis, increasing alcohol consumption was associated
      with higher high-density lipoprotein cholesterol (from a mean +/- SE of 1.57 +/-
      0.01 mmol/L in nondrinkers to 1.88 +/- 0.03 mmol/L in very high drinkers);
      triglycerides (1.17 +/- 1.01 to 1.32 +/- 1.05 mmol/L), and systolic and diastolic
      blood pressure (127.4 +/- 0.4 to 132.2 +/- 1.4 mm Hg and 78.7 +/- 0.3 to 81.7 +/-
      0.9 mm Hg, respectively) (all p values for trend <0.001). Ten-year CAD risk
      increased from 4.31 +/- 0.10% to 4.90 +/- 0.37% (p = 0.03) with alcohol use, with
      a J-shaped relation. Increasing wine consumption was more related to high-density
      lipoprotein cholesterol levels, whereas beer and spirits were related to
      increased triglyceride levels. In conclusion, as measured by 10-year CAD risk,
      the protective effect of alcohol consumption disappears in very high drinkers,
      because the beneficial increase in high-density lipoprotein cholesterol is offset
      by the increases in blood pressure levels.

PMID- 19166691
TI  - Pooled analyses of effects on C-reactive protein and low density lipoprotein
      cholesterol in placebo-controlled trials of ezetimibe monotherapy or ezetimibe
      added to baseline statin therapy.
AB  - Inflammation is associated with coronary artery disease (CAD), and statins reduce
      the inflammatory marker C-reactive protein (CRP). The effects of ezetimibe, alone
      or in combination with statins, on CRP and low-density lipoprotein (LDL)
      cholesterol were examined in 2 pooled analyses of randomized, placebo-controlled
      trials of ezetimibe 10 mg/day in patients with hypercholesterolemia: 6 12-week
      trials as monotherapy (n = 1,372) and 7 6- to 8-week trials as add-on to baseline
      statin therapy (n = 3,899). Mean percentage changes from baseline in CRP and LDL
      cholesterol were examined using analysis of variance in patients with CRP < or
      =10 mg/L. Effects within subgroups (age, gender, race, body mass index, diabetes
      mellitus, metabolic syndrome, CAD, baseline CRP or lipids, and statin potency)
      and correlations between CRP and LDL cholesterol were also examined. Reduction in
      CRP by ezetimibe monotherapy was numerically greater than with placebo (treatment
      difference 6%, p = 0.09). Added to statin therapy, ezetimibe was associated with
      a significant additional reduction in CRP (treatment difference 10%, p <0.001).
      Treatment effects were generally consistent across subgroups for the 2 analyses.
      With monotherapy and add-on to statin therapy, LDL cholesterol reduction with
      ezetimibe was significantly greater than with placebo (treatment differences -19%
      and -23%, respectively, p <0.001). Spearman's correlation coefficients among
      baseline values and percentage changes from baseline in CRP and LDL cholesterol
      ranged from -0.007% to 0.13%. In conclusion, the addition of ezetimibe to statin
      treatment provides significantly enhanced CRP reductions over and above those
      achieved with statin monotherapy. Correlations between changes in CRP and changes
      in LDL cholesterol were weakly positive and significant only when ezetimibe was
      added to statin treatment. The effects of ezetimibe monotherapy are not well
      defined. The effects of ezetimibe on CRP were consistent across patient
      subgroups.

PMID- 19166692
TI  - Usefulness of genetic polymorphisms and conventional risk factors to predict
      coronary heart disease in patients with familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant disorder with an
      associated high risk of coronary heart disease (CHD). The considerable variation
      in age of onset of CHD in patients with FH is believed to arise from conventional
      risk factors, as well as genetic variation other than in the low-density
      lipoprotein receptor gene. The degree to which currently known genetic variants
      can improve the prediction of CHD risk beyond conventional risk factors in this
      disorder was investigated. Fourteen genetic variants recently identified for
      association with CHD in a Dutch FH population were considered. Prediction models
      were constructed using Cox proportional hazards models, and predictive value was
      assessed using a concordance statistic (c statistic). A total of 1,337 patients
      with FH were completely genotyped for all genetic variants. Hazard ratios of the
      genetic variants ranged from 0.61 to 0.74 and 1.24 to 2.33. The c statistic of
      the CHD prediction model based on genetic variants was 0.59, denoting little
      discrimination. The model based on conventional risk factors had a c statistic of
      0.75, denoting moderate discrimination. Adding genetic test results to this model
      increased the c statistic to 0.76. In conclusion, the contribution of 14 genetic
      variants to the prediction of CHD risk in patients with FH was limited. To
      improve genome-based prediction of CHD, larger numbers of genetic variants need
      to be identified that either on their own or in gene-gene interaction have
      substantial effects on CHD risk.

PMID- 19166693
TI  - Ten-year all-cause mortality in presumably healthy subjects on lipid-lowering
      drugs (from the Prospective Epidemiological Study of Myocardial Infarction
      [PRIME] prospective cohort).
AB  - Lipid-lowering drugs are one of the most prescribed drugs worldwide. The aim was
      to compare 10-year all-cause mortality according to initial dyslipidemia status
      and lipid-lowering drug exposure. The PRIME study was a multicenter population
      based prospective cohort study of men recruited in 1991 to 1993, aged 50 to 59
      years at baseline, and followed up for 10 years. The 4 groups compared were
      normolipidemic, untreated dyslipidemic, and dyslipidemic subjects on fibrate or
      statin therapy. Data were analyzed using multivariate Cox models. The cohort
      included 7,722 French men (statin group 4.0%, fibrate group 7.9%, untreated
      dyslipidemic subjects 19.0%, and normolipidemic subjects 69.1%). After 10 years,
      4.8% of the sample was lost to follow-up and 416 deaths occurred (cancers 53.1%,
      cardiovascular diseases 17.1%, and other 29.8%). After adjustment for center,
      age, educational level, cardiovascular risk factors, lipids, alcohol intake, and
      history of cardiovascular and severe chronic diseases, hazard ratios (HRs) for
      all-cause mortality were 0.49 (95% confidence interval [CI] 0.26 to 0.94, p =
      0.031) for subjects treated with a statin, 0.65 (95% CI 0.42 to 0.99, p = 0.046)
      for those on fibrate therapy, and 0.76 (95% CI 0.56 to 1.03, p = 0.080) for
      normolipidemic men compared with untreated dyslipidemic subjects. In the statin
      group, HRs for death from cardiovascular disease, cancer, and other causes were
      0.55 (p = 0.348), 0.41 (p = 0.067), and 0.68 (p = 0.546) compared with
      dyslipidemic subjects, respectively. In the fibrate group, HRs were 0.76 (p =
      0.499), 0.52 (p = 0.041), and 0.87 (p = 0.746). In conclusion, in this cohort
      study carried out in a real-life setting, all-cause mortality was significantly
      lower in dyslipidemic subjects on fibrate or statin therapy than in untreated
      dyslipidemic patients. No excess risk of noncardiovascular death was observed.

PMID- 19166694
TI  - Effect of combination nicotinic acid and gemfibrozil treatment on intermediate
      density lipoprotein, and subclasses of low density lipoprotein and high density
      lipoprotein in patients with combined hyperlipidemia.
AB  - The goal of this study was to determine, using analytic ultracentrifugation, the
      effect of nicotinic acid alone or nicotinic acid added to gemfibrozil on
      lipoprotein subclass distribution, including intermediate-density lipoprotein
      (IDL; low-density to very low density flotation rate [S(f)] 12 to 20); low
      density lipoprotein (LDL) subfractions LDL-I (S(f) 7 to 12), LDL-II (S(f) 5 to
      7), LDL-III (S(f) 3 to 5), and LDL-IV (S(f) 0 to 3); and high-density lipoprotein
      (HDL) subfractions HDL(2) (high-density flotation rate 3.5 to 9.0) and HDL(3)
      (high-density flotation rate 0 to 3.5). Patients with combined hyperlipidemia
      were randomized to nicotinic acid (1,500 mg/day) plus placebo or nicotinic acid
      plus gemfibrozil (1,200 mg/d) for 12 weeks. Baseline characteristics were similar
      between the 2 groups, and mean LDL cholesterol (180 +/- 33 mg/dl) and
      triglycerides (310 +/- 126 mg/dl) were typical for patients with combined
      hyperlipidemia. Treatment with nicotinic acid resulted in a reduction in dense
      LDL (S(f) 5 to 7; p = 0.02), which was counterbalanced by an increase in buoyant
      LDL (S(f) 7 to 12; p = 0.03) that resulted in no significant LDL mass or LDL
      cholesterol change. IDL was reduced (p = 0.005) and HDL(2) increased by 143% (p =
      0.004). The combination of nicotinic acid and gemfibrozil resulted in a further
      17.8% reduction in apolipoprotein B (p = 0.06), a further 33.8% reduction in IDL
      (p = 0.06), and a greater reduction in the apolipoprotein B/apolipoprotein A-I
      ratio (p = 0.02). The combination of nicotinic acid and gemfibrozil reduced
      atherogenic by IDL 71%, dense LDL-III by 52%, and apolipoprotein B by 37% and
      increased protective HDL(2) by 90%. In conclusion, this investigation revealed
      that a combination of a fibric acid derivative and nicotinic acid offers greater
      improvement in detailed lipoprotein subclass distribution and apolipoprotein
      ratios than monotherapy.

PMID- 19166695
TI  - Once-a-week rosuvastatin (2.5 to 20 mg) in patients with a previous statin
      intolerance.
AB  - The purpose of this study was to determine the efficacy of rosuvastatin dosed
      once a week in patients with a previous statin adverse event. Rosuvastatin once a
      week was tolerated by 37 (74%) of the 50 study participants, with doses ranging
      from 2.5 mg to 20 mg a week (mean 10 +/- 4 mg). Patients tolerating the once-a
      week regimen experienced a 17% reduction in total cholesterol, 23% reduction in
      low-density lipoprotein cholesterol, 12% reduction in triglycerides, and a 5%
      increase in high-density lipoprotein cholesterol (all p <0.001), during a mean
      follow-up of 4 months +/- 2. Although this alternative dosing regimen has not
      been proven to reduce cardiovascular events, it may provide a therapeutic option
      for patients who may otherwise go without the proven benefits of statin therapy.
      In conclusion, this dosing strategy was well tolerated in patients with a history
      of an adverse event to 1 or more statins and led to significant lipoprotein
      changes.

PMID- 19166696
TI  - Left atrial function after ablation for paroxysmal atrial fibrillation.
AB  - Radiofrequency ablation of the pulmonary veins has been used to treat patients
      with paroxysmal atrial fibrillation (AF), and atrial damage after ablation is an
      issue of concern. To evaluate left atrial function shortly and midterm after
      ablation, 33 consecutive patients with paroxysmal AF were studied at baseline, 24
      hours, and > or =6 months after ablation. Patients in sinus rhythm with normal
      ventricular function were included in the study. Echocardiographic measurements
      of left atrial volumes (Simpson's rule) and transmitral and tissue Doppler
      myocardial (A') velocities at the septal and lateral mitral annulus were
      undertaken at each time. Left atrial emptying fraction (EF; maximal - minimal
      left atrial volume/maximal left atrial volume) was used to express left atrial
      function. After 8 +/- 2 months, 30 of 33 patients returned (23 men, age 53 +/- 13
      years), and all except 2 were in sinus rhythm. Shortly after ablation, left
      atrial minimal volumes increased (from 30 +/- 15 to 35 +/- 15 ml; p = 0.02), with
      maximal volumes unchanged, resulting in decreased left atrial EF (from 47 +/- 8
      to 40 +/- 7 ml; p <0.05). Tissue Doppler septal A' velocities also decreased
      (from 8.2 +/- 1.8 to 6.9 +/- 2.0 cm/s; p <0.05). However, after midterm follow
      up, both left atrial EF and septal A' velocities had slightly increased compared
      with shortly after ablation, although left atrial volumes remained similar to
      baseline. Septal A' velocity changes paralleled left atrial EF both shortly (r =
      0.46, p = 0.02) and at midterm after ablation (r = 0.47, p = 0.01). In
      conclusion, after radiofrequency ablation, patients with paroxysmal AF
      experienced an initial impairment in atrial function, with improvement at longer
      term follow-up.

PMID- 19166697
TI  - Usefulness of Type D personality and kidney dysfunction as predictors of
      interpatient variability in inflammatory activation in chronic heart failure.
AB  - Tumor necrosis factor-alpha (TNF-alpha), soluble TNF-alpha receptors 1 and 2
      (sTNFR1/2), and interleukin (IL)-6 are powerful predictors of mortality in
      chronic heart failure (CHF). Little is known, however, about the origins of
      proinflammatory cytokine production or the determinants of substantial
      interpatient variability in inflammatory activation. We prospectively examined
      kidney dysfunction and Type D personality (tendency to experience and inhibit
      emotional distress) as predictors of interpatient variability in these markers of
      inflammatory activation. At baseline, 125 patients with CHF were assessed for
      kidney dysfunction and Type D. Serum levels of proinflammatory cytokines (TNF
      alpha, sTNFR1, sTNFR2, IL-6), the anti-inflammatory cytokines IL-10, and IL-1
      receptor antagonist were measured at 1-year follow-up. Type D patients had higher
      levels of sTNFR1 (p = 0.009) and sTNFR2 (p = 0.001) and lower levels of IL-10 (p
      = 0.006) than patients without Type D and kidney dysfunction. Patients with
      kidney dysfunction also had elevated levels of sTNFR1 and sTNFR2 (p <0.0001), but
      their IL-10 level was not decreased. Type D personality and kidney dysfunction
      predicted increased sTNFR1/IL-10 and sTNFR2/IL-10 ratios (p < or =0.007); Type D
      also predicted an increased IL-6/IL-10 ratio (p = 0.013). Other predictors were
      spironolactone and older age. After adjusting for these variables, the odds for
      elevated ratios (highest 20%) were still increased in Type D patients (all odd
      ratios >3.00). In conclusion, Type D personality and kidney dysfunction
      independently predicted unfavorable cytokine profiles in patients with CHF and
      may enhance our understanding of interpatient variability in inflammatory
      activation in these patients.

PMID- 19166698
TI  - Relation of serum sodium level to long-term outcome after a first hospitalization
      for heart failure with preserved ejection fraction.
AB  - Hyponatremia is a predictor of adverse short-term outcomes in patients with acute
      heart failure (HF). The impact of hyponatremia on long-term survival in patients
      with HF with preserved ejection fraction (HFPEF) has not been evaluated. Our aim
      was to prospectively assess the impact of baseline natremia and changes in sodium
      level during hospitalization on 7-year outcome in 358 patients surviving a first
      hospitalization for HFPEF. On admission, hyponatremia (sodium <136 mEq/L) was
      diagnosed in 91 patients (25.4%). Baseline hyponatremia was associated with an
      increased risk of overall (hazard ratio [HR] 1.98, 95% confidence interval [CI]
      1.50 to 2.61) and cardiovascular mortality (HR 1.92, 95% CI 1.36 to 2.73). After
      adjustment for covariates, the relations remained significant. Seven-year
      relative survival (observed/expected survival) of hyponatremic patients was lower
      than that of patients with normal baseline natremia (31% vs 63%). The association
      of sodium and risk of death appeared linear across quartiles of baseline natremia
      and slightly stronger at the lowest of sodium values. At discharge, 45 patients
      with low baseline sodium had normal natremia (49%) and 46 had persistent
      hyponatremia (51%). Patients with normalized natremia at discharge had excess 7
      year overall mortality compared with the normonatremic group (HR 1.50, 95% CI
      1.03 to 2.19). Patients with persistent hyponatremia had the lowest 7-year
      survival (HR 2.67, 95% CI 1.89 to 3.78). After adjustment for covariates,
      patients with persistent hyponatremia had an impressive increase in relative risk
      of overall mortality compared with patients with normal baseline natremia. In
      conclusion, hyponatremia is a powerful predictor of long-term mortality in
      patients with HFPEF. Patients with HFPEF and persistent hyponatremia are at high
      risk of adverse outcomes.

PMID- 19166699
TI  - Differentiation of hypertrophic cardiomyopathy and cardiac amyloidosis from other
      causes of ventricular wall thickening by two-dimensional strain imaging
      echocardiography.
AB  - Hypertension is the most common cause of left ventricular (LV) hypertrophy.
      However, multiple causes can lead to LV hypertrophy, each of which has different
      histological and mechanical properties. To assess the value of a novel speckle
      tracking echocardiographic measurement of myocardial strain and strain rate in
      defining the mechanical properties of LV hypertrophy, 20 patients with asymmetric
      hypertrophic cardiomyopathy, 24 patients with secondary LV hypertrophy, 12
      patients with biopsy-proved confirmed cardiac amyloidosis, and 22 age-matched
      healthy asymptomatic volunteers were studied. Patients with amyloidosis had
      severe diastolic dysfunction, and myocardial deformation was significantly
      decreased. The new technique allowed cardiac amyloid to be easily differentiated
      from the other categories. In patients with hypertrophic cardiomyopathy, there
      was segmental myocardium dysfunction as assessed by strain imaging. LV global
      systolic velocity and radial displacement were higher, and abnormal relaxation
      was more frequent, in the group with secondary LV hypertrophy than in normal
      controls. In conclusion, the observations from strain parameters derived from
      speckle tracking were consistent with the known underlying pathology of each
      condition, which speaks to the value of strain imaging. Cardiac amyloid
      profoundly alters all strain parameters, and analysis of these parameters could
      aid in the diagnosis.

PMID- 19166700
TI  - Prenatal diagnosis and outcome of isolated vascular rings.
AB  - The purpose of this study was to describe our experience in the ultrasound
      visualization and management of prenatally diagnosed isolated vascular rings.
      From January 2002 to December 2007, a total of 19 fetuses had a sonographic
      diagnosis of isolated vascular rings in 2 reference centers at a mean gestational
      age of 23 weeks. There were 8 cases of left aortic arch with aberrant right
      subclavian artery, 5 cases of double aortic arch, and 6 cases of right aortic
      arch with aberrant left subclavian artery. Two fetuses had associated trisomy 21
      and 1 had a 22q11 microdeletion. Parents chose to terminate the pregnancy in all
      cases. Four patients successfully underwent surgical correction, and in 1
      patient, tracheoplasty was also performed. In conclusion, isolated vascular rings
      can be accurately diagnosed prenatally by using the "3-vessel and trachea view"
      and "supra-aortic-branch view" that allow detection of vascular structures
      running around the trachea. Karyotyping and prenatal testing for 22q11
      microdeletions should be offered to all parents. Affected children should undergo
      surgical correction as soon as symptoms of tracheal compression appear, avoiding
      tracheomalacia. Associated congenital tracheal stenosis should be excluded before
      surgery.

PMID- 19166701
TI  - Adverse left ventricular mechanics in adults with repaired tetralogy of Fallot.
AB  - Left ventricular (LV) dysfunction is a predictor of adverse outcomes in patients
      with repaired tetralogy of Fallot (TOF). However, the mechanisms for LV
      dysfunction are not well understood. The aim of the study was to determine
      whether the prolonged QRS duration of right branch bundle block was associated
      with adverse LV mechanics. Seventy-five patients (mean age 31 +/- 2 years) with
      repaired TOF were studied. LV and right ventricular (RV) volumes and ejection
      fractions (EFs) were assessed using cardiac magnetic resonance imaging. Vector
      velocity imaging was used to assess longitudinal strain and intraventricular
      dyssynchrony. Prolonged QRS duration was associated with increased RV and LV
      dimensions (p = 0.01) and decreased function (RVEF r = -0.60, p <0.001 and LVEF r
      = -0.77, p <0.001). In addition, prolonged QRS duration was associated with
      heterogeneous ventricular mechanical activation and reduced strain in the lateral
      and septal left ventricle walls. Degree of intraventricular dyssynchrony
      correlated with LVEF (r = -0.59, p <0.001), QRS duration (r = 0.74, p <0.001),
      and septal strain (r = 0.70, p <0.001). In conclusion, LV dysfunction and
      dyssynchrony were observed in patients with TOF and were associated with QRS
      duration. It was possible that abnormal LV mechanics in combination with RV
      dysfunction may explain the relation between QRS duration and adverse cardiac
      outcomes.

PMID- 19166702
TI  - Adverse consequences of the 50% misconception.
AB  - It is often claimed that only 50% of the incidence of coronary artery disease in
      the population can be attributed to the standard major risk factors. A careful
      review of published research demonstrates that 75% to 90% of coronary artery
      disease incidence in a variety of populations is explained by the standard
      modifiable risk factors. In conclusion, these data suggest that a more rigorous
      focus on these conventional risk factors and the lifestyle behaviors that promote
      them has great potential to reduce the burden of coronary artery disease
      worldwide.

PMID- 19166703
TI  - Memorable cardiology quotes.

PMID- 19166704
TI  - Fifty years of hypertrophic cardiomyopathy.

PMID- 19166705
TI  - Relation of body mass index to five-year survival in patients with ST-elevation
      myocardial infarction.

PMID- 19166706
TI  - Emerging insights on antiplatelet therapy. Introduction.

PMID- 19166707
TI  - Role of platelets in atherothrombosis.
AB  - Platelets play a pivotal role in atherothrombosis and therefore are primary
      targets of antithrombotic therapy. They release an array of agonists, such as
      adenosine diphosphate (ADP); adhesive molecules, such as P-selectin,
      thrombospondin, fibrinogen, and von Willebrand factor; coagulation factors; and
      growth factors. In turn, they present transmembrane receptors for a plethora of
      agonists and ligands. Heterodimeric glycoproteins of the integrin family bind
      extracellular matrix and plasma proteins; mediate adhesion, activation,
      spreading, and aggregation; and facilitate intercellular bidirectional signal
      transduction. Glycoprotein IIb/IIIa is the most abundant platelet integrin and
      membrane surface glycoprotein. Glycolipids, heparins, proteoglycans,
      tetraspanins, and a multitude of other molecules, such as tumor necrosis factor
      alpha, CD40L, growth arrest-specific 6, Eph receptor tyrosine kinases, and
      signaling lymphocytic activation molecule receptors, have been implicated in
      atherothrombosis. ADP promotes platelet aggregation by binding to platelet
      surface receptors P2Y(1) and P2Y(12); the thienopyridines inhibit aggregation by
      binding covalently to P2Y(12). Thrombin, a potent initiator of platelet
      aggregation, activates platelets by cleaving protease-activated receptors (PARs)
      PAR-1 and PAR-4 and further propagates its effect by activating nearby platelets.
      A number of pharmacologic agents with antiplatelet actions have been developed,
      but the search continues for agents that strike an optimal balance between
      control of thrombosis and serious bleeding.

PMID- 19166708
TI  - Role of antiplatelet therapy across the spectrum of patients with coronary artery
      disease.
AB  - Antiplatelet therapy is an important treatment modality across the spectrum of
      coronary artery disease manifestations. The role of aspirin in primary prevention
      continues to be refined. Although monotherapy with either aspirin or clopidogrel
      has been validated in secondary prevention, for high-risk patients such as those
      with acute coronary syndromes or requiring percutaneous coronary intervention,
      dual antiplatelet therapy appears to be most beneficial. Questions remain about
      the appropriate duration of dual antiplatelet therapy, especially in patients
      with prior ischemic events or in those receiving first-generation drug-eluting
      stents, with indirect evidence suggesting longer durations are better.

PMID- 19166709
TI  - Methods for the measurement of platelet function.
AB  - This article discusses the advantages and disadvantages of methods for the
      measurement of platelet function. The focus is on tests that can be used to
      monitor antiplatelet activity in the setting of cardiovascular disease and
      potentially predict thrombosis and bleeding. The tests described are platelet
      aggregometry; impedance aggregometry; VerifyNow (Accumetrics, San Diego, CA);
      Plateletworks (Helena Laboratories, Beaumont, TX); platelet surface P-selectin,
      platelet surface-activated glycoprotein IIb/IIIa, and leukocyte-platelet
      aggregates; TEG Platelet Mapping system (Haemoscope, Niles, IL); Impact cone and
      plate(let) analyzer (DiaMed, Cressier, Switzerland); Platelet Function Analyzer
      100 (Siemens Healthcare Diagnostics, Inc., Deerfield, IL); phosphorylation of
      vasodilator-stimulated phosphoprotein; serum thromboxane B(2); and urinary 11
      dehydro thromboxane B(2). Some of the factors that differentiate these tests are
      sample volume requirements, the use of whole blood, the presence of shear, point
      of-care status, need for a technician, and expense.

PMID- 19166710
TI  - Variability in responsiveness to oral antiplatelet therapy.
AB  - Patients who have acute coronary syndromes or are undergoing percutaneous
      coronary intervention receive antiplatelet therapy to reduce the risk of
      atherothrombotic complications. Current guidelines favor the use of aspirin in
      combination with clopidogrel based on the results of a number of large-scale
      clinical trials. Aspirin alone is a relatively weak antiplatelet agent because it
      inhibits only one of many paths to platelet activation. By blockade of an
      adjunctive signaling pathway, the addition of clopidogrel to aspirin leads to
      synergistic platelet inhibitory effects. Dual antiplatelet therapy reduces the
      number of patients who experience adverse cardiovascular outcomes by 20% over
      aspirin alone. Nevertheless, approximately 10% of patients experience further
      atherothrombotic events, even while receiving dual antiplatelet therapy.
      Variability in individual responsiveness, including "resistance," has been
      attributed to the occurrence of these events. This article discusses variability
      in individual responses to oral antiplatelet therapy and its implications for
      clinical outcomes.

PMID- 19166711
TI  - Monitoring platelet function to reduce the risk of ischemic and bleeding
      complications.
AB  - Patients with acute coronary syndromes and patients who undergo coronary stent
      implantation frequently receive dual antiplatelet therapy with aspirin and a
      thienopyridine. A wide variability exists in the inhibitory response to the
      thienopyridine clopidogrel among individuals, but this variability can be
      detected by a variety of platelet function assays. Several studies have
      demonstrated an association between high platelet reactivity post clopidogrel and
      subsequent cardiac events. To be adopted into routine clinical practice, platelet
      function assays must not only be able to identify at-risk patients, but they must
      also determine the appropriate thresholds for nonresponsiveness that provide
      appropriate sensitivity and specificity for subsequent adverse events.
      Prospective, randomized trials should determine whether therapeutic interventions
      guided by platelet function tests can safely and effectively reduce thrombotic
      events in at-risk patients. The use of platelet function monitoring to guide the
      timing of surgery after the discontinuation of antiplatelet therapy also merits
      further study.

PMID- 19166712
TI  - Advances in antiplatelet therapy: agents in clinical development.
AB  - Antiplatelet agents are the cornerstone of treatment for patients with acute
      coronary syndromes and patients undergoing percutaneous coronary intervention.
      The current "gold standard" consists of a combination of aspirin and clopidogrel
      administered orally shortly before invasive procedures and then continued in the
      form of maintenance doses. Not all patients respond optimally to standard
      therapy. Resistance to the antiplatelet activity of both drugs when used either
      singly or in combination has been observed and may lead to treatment failure,
      including further atherothrombotic events. Potential limitations associated with
      the combined use of aspirin and clopidogrel have inspired clinical investigation
      into several promising new antiplatelet agents as potential additions or
      alternatives to standard therapy. The candidates include prasugrel, which has a
      mechanism similar to that of clopidogrel but with superior pharmacokinetics;
      ticagrelor, a nonthienopyridine that binds reversibly to the platelet P2Y(12)
      receptor; cangrelor, an intravenously administered analogue of ticagrelor; and
      various thrombin receptor antagonists.

PMID- 19166713
TI  - Uveitis in patients with autoimmune hepatitis.
AB  - PURPOSE: To report seven cases of uveitis occurring in patients with autoimmune
      hepatitis (AIH), raising the possibility that uveitis may be an extrahepatic
      feature of AIH. DESIGN: Multicenter, retrospective, observational case series of
      patients with AIH and uveitis. METHODS: One index case was identified at Oregon
      Health & Science University. Further cases were identified by a web-based survey
      of members of the American Uveitis Society, the International Uveitis Study
      Group, the Proctor Foundation mailing list server, and the First SUN
      International Workshop. Respondents were asked to provide clinical information
      about uveitis phenotype, AIH features, and treatment. RESULTS: Clinical
      information was obtained for seven individuals (four females and three males; age
      range, seven to 67 years) who suffered from AIH and uveitis. Average duration of
      follow-up was 5.5 years. All patients had chronic, persistent bilateral uveitis
      that was anterior (n = 3), intermediate (n = 1), or pan (n = 3) in location.
      Every patient had complications arising from his or her uveitis, including
      cataract (n = 5), glaucoma (n = 3), cystoid macular edema (n = 3), and posterior
      synechiae (n = 3). Final visual acuities ranged from 20/16 to hand movements. To
      treat the uveitis and/or AIH, the majority of patients required oral prednisone
      and all seven patients were treated with systemic immunosuppression. CONCLUSION:
      Despite the small size of this study, our findings suggest an association between
      AIH and uveitis. The uveitis is chronic, bilateral, and associated with sight
      threatening complications, necessitating systemic immunosuppression in some
      individuals.

PMID- 19166715
TI  - The need for standardization of antiretinal antibody detection and measurement.

PMID- 19166716
TI  - Anti-Vascular Endothelial Growth Factor Injection for Exudative Age-related
      Macular Degeneration in Patients with Vitreo-Macular Traction.

PMID- 19166718
TI  - Improvements of reliability for methylmercury determination in environmental
      samples.
AB  - The determination of methylmercury (MeHg) in environmental samples by ethylation
      derivation-gas chromatography-atomic fluorescence spectrometry (ED-GC-AFS) is
      associated with an intimate problem of water moisture accumulation introduced in
      the ethylation step, which enters the detection system and cause a spectroscopic
      interference. With a simple modification on the GC-AFS system, this problem was
      eliminated and the analytical quality of the measurements was significantly
      improved. The presence of dissolved sulfide in samples can also cause serious
      chemical interference in the ethylation step resulting in lower or total loss of
      the MeHg signal. It was found that a masking system of CuSO(4)-Na(2)C(2)O(4) was
      able to eliminate this interference. With this system, the accurate determination
      of trace amount of MeHg in high dissolved sulfide containing samples was
      achieved. Satisfactory analytical results were obtained with the certified
      reference sediment IAEA405, sulfate reducing bacteria culture and sulfide
      containing water samples. The limit of detection and quantitation of this masking
      system is 0.01 and 0.04ngL(-1) respectively. Other factors affecting ethylation
      are also discussed.

PMID- 19166719
TI  - Study of essential element accumulation in the leaves of a Cu-tolerant plant
      Elsholtzia splendens after Cu treatment by imaging laser ablation inductively
      coupled plasma mass spectrometry (LA-ICP-MS).
AB  - Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used
      for the quantitative imaging of Cu and other essential elements (such as K, Mg,
      Mn, P, S and B) in the leaves of a Cu-tolerant plant Elsholtzia splendens treated
      with the enriched (65)Cu isotope tracer (isotope abundance of 89.2%). The leaves
      (newly formed, fully grown and oldest) were scanned directly with a focused
      Nd:YAG laser in the laser ablation chamber. The ablated material was transported
      with argon as carrier gas to a quadrupole-based ICP-MS (ICP-QMS), and the ion
      intensities of (65)Cu(+), (39)K(+), (24)Mg(+), (55)Mn(+), (31)P(+), (34)S(+) and
      (11)B(+) were measured by ICP-QMS to study the accumulation of Cu and other
      elements of interest. Standard reference material NIST SRM 1515 Apple Leaves
      doped with known concentrations of analytes (from 0.1 to 2000mgL(-1)) was
      measured together with the samples by LA-ICP-MS and was used for the
      quantification of the analytical data. Notable accumulation of Cu in the newly
      formed leaves was clearly identified by imaging LA-ICP-MS. The increased isotope
      ratios of (65)Cu/(63)Cu measured by LA-ICP-MS demonstrated the path of Cu uptake
      and accumulation via the petiole and main veins in the leaves. Cu stress-induced
      accumulation of K, Mg, Mn, P and S in the newly formed leaves was observed, while
      B was not significantly affected. In the present study, the concentrations of K,
      Mg, Mn, P and S were not obviously changed in the fully grown leaves after short
      term treatment. Along with the treatment, a visible decrease of K and P was found
      in the oldest leaves, while other elements were not influenced by Cu stress.

PMID- 19166720
TI  - Multivariate calibration analysis of colorimetric mercury sensing using a
      molecular probe.
AB  - Selectivity is one of the main challenges of sensors, particularly those based on
      chemical interactions. Multivariate analytical models can determine the
      concentration of analytes even in the presence of other potential interferences.
      In this work, we have determined the presence of mercury ions in aqueous
      solutions in the ppm range (0-2mgL(-1)) using a ruthenium bis-thiocyanate complex
      as a chemical probe. Moreover, we have analyzed the mercury-containing solutions
      with the co-existence of higher concentrations (19.5mgL(-1)) of other potential
      competitors such as Cd(2+), Pb(2+), Cu(2+) and Zn(2+) ions. Our experimental
      model is based on partial least squares (PLS) method and other techniques as
      genetic algorithm and statistical feature selection (SFS) that have been used to
      refine, beforehand, the analytical data. In summary, we have demonstrated that
      the root mean square error of prediction without pre-treatment and with
      statistical feature selection can be reduced from 10.22% to 6.27%.

PMID- 19166721
TI  - Complexes of tetra-tert-butyl-tetraazaporphine with Al(III) and Zr(IV) cations as
      fluoride selective ionophores.
AB  - In this work, complexes of Zr(IV) and Al(III) cations with 2,7,12,17-tetra-tert
      butyl-5,10,15,20-tetraazaporphine (TAP) were tested as ionophores in plasticized
      PVC membranes of ion-selective electrodes. It was found that both tested
      ionophores show enhanced affinity towards fluoride anion. High fluoride
      selectivity was observed in the presence of anionic or cationic additives in the
      membrane, which indicates that proposed compounds work according to charged or
      neutral carrier mechanism, depending on membrane composition and pretreatment.
      tert-Butyl substituents, present in the structure of tested compounds, were
      supposed to prevent formation of ionophore dimers within the membrane phase. This
      process was found to be responsible for some unfavorable potentiometric
      properties of electrodes based on complexes of Zr(IV) and Al(III) cations with
      porphyrins (compounds closely related to tetra-tert-butyl-5,10,15,20
      tetraazaporphine). As it was shown using spectrophotometrical measurements,
      Al(III)-TAP was not susceptible to dimerization, while dimer formation was
      observed for Zr(IV)-TAP. In full agreement with these observations, electrodes
      with membranes containing Al(III)-TAP responded in near-Nernstian and fast manner
      towards fluoride anion, while the employment of Zr(IV)-TAP as ionophore resulted
      in super-Nernstian and sluggish response. Plasticized PVC membranes doped with
      Al(III)-TAP and 20mol% of lipophilic anionic additives shown remarkable F(-)
      selectivity, with selectivity coefficients, logK(F-pot.).(Y-), as follows: -4.4
      (Y(-)Br(-)), -4.3 (Cl(-)), -4.2 (NO(3)(-)), -3.6 (SCN(-)), -2.9 (ClO(4)(-)).

PMID- 19166722
TI  - Pressurized liquid extraction and anticholinesterase activity-based thin-layer
      chromatography with bioautography of Amaryllidaceae alkaloids.
AB  - Modern extraction technique-pressurized liquid extraction (PLE) was optimised for
      extraction of lycorine and galanthamine (Amaryllidaceae alkaloids) from Narcissus
      jonquilla 'Pipit'. Crude extracts were purified on Oasis MCX cartridges, and the
      alkaloids eluted with 80-100% recoveries using methanol-10% ammonia solution
      (3:1, v/v). Quantitative results were obtained by both HPTLC-densitometry on
      silica gel plates and RP-HPLC with diode array (DAD) on XTerra C(18) stationary
      phase. Both methods were fully validated in terms of specificity, precision
      (including intra- and inter-day measurements), LOD and LOQ values, correlation of
      UV spectra and linearity of calibration curves. The methods were also well
      correlated each other with correlation coefficients (r) 0.98823 and 0.99081,
      respectively, for the mean values of galanthamine and lycorine. Among the
      investigated solvents methanol and 1% tartaric acid methanolic solution at
      default conditions (120 degrees C, p=60bar, time: 10min, one static cycle) permit
      the highest yields of the total sum of the alkaloids, whereas for toluene the
      lowest amounts were measured. Lycorine to galanthamine mean ratios were dependant
      on the type of solvent used, and in toluene galanthamine and related alkaloids
      were preferably extracted. In temperature experiments for galanthamine, the
      levels of this compound increased from the temperature of 20 till 150 degrees C
      in the investigated solvent systems, then decreased with slight increase from the
      temperature of 175 to 200 degrees C in 1% tartaric acid methanolic solution. When
      lycorine was analysed, similar trends were observed, however the maximum of the
      concentration was measured at a temperature about 125 degrees C. The ratios of
      the mean values of these two compounds differed in temperature-dependant
      experiments in both solvent systems. Further more, two TLC with bioautography
      approaches were used in screening for anticholinesterese properties of the
      extracts. No qualitative differences were found among the different solvent
      extracts, and AChE inhibition was correlated with galanthamine and related
      compounds. In conclusion, optimised PLE was much more effective than previously
      applied hot-solvent extraction, microwave-assisted extraction (MAE) or ultrasound
      assisted extraction (USAE).

PMID- 19166723
TI  - An organically modified silicate molecularly imprinted solid-phase
      microextraction device for the determination of polybrominated diphenyl ethers.
AB  - An organically modified silicate (ORMOSIL) SPME stationary phase molecularly
      imprinted with BDE-209 has been successfully fabricated by conventional sol-gel
      technique from phenyltrimethoxysilane and tetraethoxysilane. The thickness of the
      ORMOSIL-SPME stationary phase, on fused-silica optical fibres, was measured to be
      ca. 9.5 microm with a volume of ca. 0.12 microL. Rebinding assays and Scatchard
      analysis revealed that the imprinted ORMOSIL-SPME stationary phase possessed a
      binding affinity, K(B), of 7.3+/-1.7 x 10(10)M(-1) for BDE-209, with a receptor
      site density, B(max), of 1.2 x 10(-3)pmol per SPME device. Besides its molecular
      template, the ORMOSIL-SPME stationary phase also showed good affinity
      (logK(B)>/=9.5) for smaller BDE congeners commonly found in the natural
      environment. The density of receptor sites within the imprinted matrix for those
      smaller BDE congeners was even higher than that for BDE-209. This may be
      attributable to the binding site heterogeneity of the imprinting process that
      creates deformed binding sites that are suitable for the accommodation of the
      smaller BDE congeners. Compared to the commercially available polyacrylate and
      polydimethylsiloxane SPME stationary phases, the imprinted ORMOSIL-SPME devices
      showed much higher pre-concentration ability towards polybrominated diphenyl
      ethers (PBDEs), even in direct immersion sampling at room temperature. Coupled
      with GC-NCI-MS and GC-muECD, the imprinted ORMOSIL-SPME device was able to
      achieve detection sensitivity of 0.2-3.6 pgmL(-1) and 1-8.8 pgmL(-1),
      respectively, for commonly occurring BDE congeners, including medium to high
      molecular weight PBDEs. The imprinted ORMOSIL-SPME device has been successfully
      applied to monitor PBDE contents in municipal wastewaters.

PMID- 19166724
TI  - Comparison of sample preparation methods for analysis of isoflavones in
      foodstuffs.
AB  - Due to the lack of one universally applicable and commonly used reference method,
      sample preparation in isoflavone (IF) analysis has been performed by many
      different methods which renders comparison and quality assessment of published IF
      contents in foodstuffs difficult. In the present work, the impact of different
      experimental parameters on the IF concentrations determined in soybeans, tofu,
      soy drink and textured vegetable protein by different extraction and hydrolysis
      methods was assessed and IF contents obtained by optimized orthogonal methods
      were compared. Chromatographic analysis was performed by HPLC-UV-ESI-MS. If
      possible sources of error - which are also pointed out in this work - are
      avoided, IF contents obtained by extraction, acid-, base- and enzymatic
      hydrolysis are similar. However, these sample preparation methods differ in the
      amount of time, standard compounds and instruments required, ruggedness, and in
      their applicability to analysis of complex composite samples containing soy as
      minor ingredient. Enzymatic hydrolysis with Helix pomatia juice after extraction
      by sonication with first 50, then 80% aqueous acetonitrile in the presence of
      zinc sulfate heptahydrate and after adjustment to </=10% organic solvent turned
      out to be the method of choice if only aglucone equivalent contents are required.
      The advantages of this method are short chromatographic run times, smallest
      danger of coelution, lowest achievable limits of quantitation and therefore best
      suitability for work-up of complex composite samples and that only aglucone
      standards are needed for quantitation.

PMID- 19166725
TI  - Development of a derivatisation method for the analysis of aldehyde modified
      amino acid residues in proteins by Fourier transform mass spectrometry.
AB  - A method was developed for the analysis of amino acids within bovine serum
      albumin (BSA) which had been modified by reaction with different enals. BSA was
      reacted with the aldehydes and the reaction products were stabilised by reaction
      with NaBH(4). The protein was then hydrolysed with 6N HCl and the hydrolysis
      products were analysed by liquid chromatography-mass spectrometry (LC-MS). The
      modified amino acids were derivatised with propylchloroformate. High resolution
      mass spectrometry carried out using an LTQ-Orbitrap instrument which was able to
      characterise a wide range of adducts. In addition double adducts were observed to
      be formed with 4-hydroxynonenal (HNE) and lysine or lysine+histidine.
      Qualitatively it was possible to consistently observe a pyridinium adduct formed
      between lysine and pentenal in human plasma from normal subjects.

PMID- 19166726
TI  - Comparison of different amino acid derivatives and analysis of rat brain
      microdialysates by liquid chromatography tandem mass spectrometry.
AB  - The efficiencies of three derivatisation reagents that react with either the
      amine (9-fluorenylmethyl chloroformate (FMOC)) or the carboxylic acid group
      (butanol) of amino acid or with both types of functional groups (propyl
      chloroformate) were compared in the analysis of amino acids by liquid
      chromatography-electrospray-tandem mass spectrometry (LC-ESI-MS/MS). Separation
      of 20 amino acids derivatised with these three reagents was studied on reversed
      phase chromatography. Linearity, repeatability and limits of detection of the LC
      ESI-MS/MS method were determined by analysing FMOC-, butanol- and propyl
      chloroformate-derivatised lysine, beta-aminobutyric acid, threonine and glutamic
      acid. The limits of detection for the derivatised amino acids (7.5-75fmol) were
      as much as 2-60 times lower than those of the corresponding underivatised
      molecules. The best linearity was observed for amino acids derivatised with
      propyl chloroformate or butanol (r(2)=0.996-0.999, range=100-8500nmolL(-1)).
      Propyl chloroformate was the best suited of the reagents tested for the analysis
      of amino acids with LC-MS/MS and was used for the analysis of amino acids in rat
      brain microdialysis samples.

PMID- 19166727
TI  - Positive mode electrospray ionization mass spectrometry of bisphosphonates using
      dicationic and tricationic ion-pairing agents.
AB  - A general method for detecting bisphosphonate drugs by ESI-MS and LC-ESI-MS as
      positive ions has been developed. Bisphosphonates can have multiple negative
      charges in solution. Tricationic ion-pairing reagents were paired with
      bisphosphonates to form a positively charged complex. It was clear that this
      facile pairing method worked. However, an appreciable presence of -1
      bisphosphonate species were observed in positive mode ESI-MS (i.e. as the +2
      complex with tricationic reagents). This led to an extended investigation on the
      use of dicationic pairing agents. The use of dicationic reagents improved the
      detection sensitivity for all of the bisphosphonates. Tandem mass spectrometry
      also improved the limits of detection for most of the bisphosphonates using both
      the tricationic and dicationic pairing reagents. A tricationic reagent also was
      used as an ion-pairing reagent in chromatography experiments. Thus the addition
      of a single reagent produced benefits in that it increased chromatographic
      retention and enhanced the ESI-MS detection of bisphosphonates.

PMID- 19166728
TI  - Mode-filtered light methane gas sensor based on cryptophane A.
AB  - A mode-filtered light sensor has been developed for methane (CH(4)) gas
      determination at ambient conditions. The proposed chemosensor consisted of an
      annular column which was constructed by inserting an optical fiber coated with a
      thin silicone cladding of cryptophane A into a fused-silica capillary. When CH(4)
      was introduced to the sensor, selective inclusion of CH(4) into the silicone
      layer would cause a change in the local refractive index of the cladding,
      resulting in the change of mode-filtered light that emanated from the fiber.
      Three detection windows were set alongside the capillary to propagate the light
      to a charge-coupled device (CCD). The changes of mode-filtered light on exposure
      to various concentrations of CH(4) were thus simultaneously monitored. The mode
      filtered light intensity decreased with the increase in concentration of CH(4).
      The dynamic concentration range of the sensor for CH(4) was 0.0-16.0% v/v with a
      detection limit of 0.15% v/v. The highest sensitivity was found at the channel
      furthest away from the excitation light source. The response time (t(95%)) was
      about 5min. The reproducibility was good with a relative standard deviation (RSD)
      of less than 7% from evaluating six cryptophane A-coated fibers. Oxygen, hydrogen
      and carbon dioxide showed very little interference on detection but interferences
      from dichloromethane and carbon tetrachloride were observed. The proposed mode
      filtered light sensor has been successfully applied to determine CH(4) samples
      and the accuracy was good. Our work offers a promising approach for CH(4)
      detection.

PMID- 19166729
TI  - Ferrocenyl-doped silica nanoparticles as an immobilized affinity support for
      electrochemical immunoassay of cancer antigen 15-3.
AB  - The aim of this study is to elaborate a simple and sensitive electrochemical
      immunoassay using ferrocenecarboxylic (Fc-COOH)-doped silica nanoparticles (SNPs)
      as an immobilized affinity support for cancer antigen 15-3 (CA 15-3) detection.
      The Fc-COOH-doped SNPs with redox-active were prepared by using a water-in-oil
      microemulsion method. The use of colloidal silica could prevent the leakage of Fc
      COOH and were easily modified with trialkoxysilane reagents for covalent
      conjugation of CA 15-3 antibodies (anti-CA 15-3). The Fc-COOH-doped SNPs were
      characterized by X-ray photoelectron spectroscopy (XPS) and transmission electron
      microscopy (TEM). The fabrication process of the electrochemical immunosensor was
      demonstrated by using cyclic voltammetry (CV) and electrochemical impedance
      spectroscopy (EIS) techniques. Under optimal conditions, the developed
      immunosensor showed good linearity at the studied concentration range of 2.0-240
      UmL(-1) with a coefficient 0.9986 and a detection limit of 0.64 UmL(-1) at S/N=3.

PMID- 19166730
TI  - Analysis of omeprazole and its main metabolites by liquid chromatography using
      hybrid micellar mobile phases.
AB  - Omeprazole is a selective inhibitor of gastric acid secretion and is one of the
      most widely prescribed drugs internationally. A chromatographic procedure that
      uses micellar mobile phases of sodium dodecyl sulphate and propanol buffered at
      pH 7 and a C18 column is reported for the determination of omeprazole and its
      principal metabolites (omeprazole sulphone and hydroxyomeprazole) in urine and
      serum samples. In this work, direct injection and UV detection set at 305 nm was
      used. Omeprazole and its metabolites were eluted in less than 11min with no
      interference by the protein band or endogenous compounds. Adequate resolution was
      obtained with a chemometric approach, in which the retention factor and shape of
      the chromatographic peaks were taken into account. The analytical parameters
      including linearity (r>0.9998), intra- and inter-day precision (RSD, %: 0.6-7.9
      and 0.14-4.7, respectively) and robustness were studied in the validation of the
      method for the three compounds. The limits of detection and quantification were
      less than 6 and 25ngmL(-1), respectively. Recoveries in micellar medium, plasma
      and urine matrices were in the 98-102% range. Finally, the method was
      successfully applied to the determination of omeprazole and its metabolites in
      physiological samples. Omeprazole was also analysed in pharmaceutical
      formulations.

PMID- 19166732
TI  - Comprehensive two-dimensional gas chromatography for fingerprint pattern
      recognition in olive oils produced by two different techniques in Portuguese
      olive varieties Galega Vulgar, Cobrancosa e Carrasquenha.
AB  - For olive oil production a metal hammer-decanter olive processing line was
      compared to a traditional metal hammer-press line, a discontinuous method which,
      if properly used, yields high-quality virgin olive oils. Galega, Carrasquenha and
      Cobrancosa olives (traditional Portuguese varieties) were studied. The analysis
      of the aroma compounds was performed after headspace-solid phase micro
      extraction. The analytical results obtained after comprehensive gas
      chromatography in tandem with time of flight mass spectrometry (GCxGC/ToFMS) for
      these three different olive oil varieties, from a single year harvest and
      processed with two different extraction technologies, were compared using
      statistical image treatment, by means of ImageJ software, for fingerprint
      recognitions and compared with principal component analysis when the area data of
      each chromatographic spot of the contour plots were considered. The differences
      used to classify the olive oils studied under different groups after principal
      component analysis were observed independently of the treatment used (peak areas
      or the sum of the pixels counts). When the individual peak areas were considered,
      more then 75.7% of the total variance is explained by the first two principal
      components while in the case where the data were subjected to image treatment
      84.0% of the total variance is explained by the first two principal components.
      In both cases the first and second principal components present eigenvalues
      higher then 1.0. Fingerprint image monitoring of the aroma compounds of the olive
      oil allowed a rapid differentiation of the three varieties studied as well as the
      extraction methods used. The volatile compounds responsible for their
      characterization were tentatively identified in a bi-dimensional polar/non-polar
      column set in the GCxGC/Tof-MS apparatus. This methodology allowed the reduction
      of the number of compounds needed for matrices characterization, preserving the
      efficiency of the discrimination, when compared with the traditional methods
      where the identification of all peaks is needed.

PMID- 19166731
TI  - Comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry
      for metabonomics: Biomarker discovery for diabetes mellitus.
AB  - Comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry
      (GCxGC-TOFMS) coupled with pattern recognition methods was applied to analyze
      plasma from diabetic patients and healthy controls. After sample preparation and
      GCxGC-TOFMS analysis, collected data were transformed, the peak alignment between
      different chromatograms was performed to generate the metabolites' peak table,
      then orthogonal signal correction filtered partial least-squares discriminant
      analysis (OSC-PLSDA) was carried out to model the data and discover metabolites
      with a significant concentration change in diabetic patients. With the method
      above, diabetic patients and healthy controls could be correctly distinguished
      based on the metabolic abnormity in plasma. Five potential biomarkers including
      glucose, 2-hydroxyisobutyric acid, linoleic acid, palmitic acid and phosphate
      were identified. It was found that elevated free fatty acids were essential
      pathophysiological factors in diabetes mellitus which reflected either the
      hyperglycemia or the deregulation of fatty acids metabolism. These potential
      biomarkers in plasma, e.g. palmitic acid, linoleic acid and 2-hydroxybutyric acid
      might be helpful in the diagnosis or further study of diabetes mellitus. This
      study shows the practicability and advantage of GCxGC-TOFMS coupled with data
      analysis and mining for metabonomics in biomarker discovery.

PMID- 19166733
TI  - Development of a validated liquid chromatographic method for the quality control
      of Prunellae Spica: determination of triterpenic acids.
AB  - A simple and rapid reversed-phase HPLC-UV method was developed for the
      determination of triterpenic acids in the crude extract of Prunellae Spica. Five
      triterpenic acids were extracted and isolated from P. Spica as marker compounds
      for use in the quality control of herbal medicines. Various solvent extraction
      techniques were evaluated, and the greatest efficiency was observed with
      sonication in 100% ethanol. Elemental compositions of the five marker compounds
      were determined by high-resolution mass spectroscopy. The dynamic range of the
      HPLC-UV method depended on the specific analyte, and acceptable quantitation was
      obtained between 10 and 250 microgmL(-1) for oleanolic acid, between 10 and 300
      microgmL(-1) for ursolic acid, between 3 and 75 microgmL(-1) for 2alpha,3alpha,24
      trihydroxyolean-12en-28oic acid, between 5 and 100 microgmL(-1) for euscaphic
      acid, and between 5 and 100 microgmL(-1) for 2alpha,3alpha-dihydroxyurs-12en
      28oic acid. The method was deemed satisfactory by inter- and intra-day validation
      and exhibited both high accuracy and precision (relative standard deviation
      <9.4%). Overall limits of quantitation and detection were approximately 0.5-2.5
      microgmL(-1) at a signal-to-noise ratio (S/N) of 3 and were about 3.0-10.0
      microgmL(-1) at a S/N of 10. In addition, principal component analysis (PCA) was
      performed on the analytical data of 15 different P. Spica samples in order to
      classify samples collected from different regions.

PMID- 19166734
TI  - Determination of anthracene by real-time immuno-polymerase chain reaction assay.
AB  - A reliable and sensitive competitive real-time immuno-PCR (RT-IPCR) assay for the
      determination of anthracene (AN) was developed. 9-Anthracenebutanoic acid, gamma
      oxo-(ANA) was synthesized as the hapten of AN. Mixed anhydride reaction (MAR) was
      used to couple the ANA to ovalbumin (OVA) to form artificial coating antigen.
      Active ester method (AEM) was used to couple the ANA to bovine serum albumin
      (BSA) to form artificial immune antigen. Male New Zealand white rabbits were
      immunized with immune antigen to obtain polyclonal antibodies (pAbs), with which,
      a novel RT-IPCR assay for determination of AN was described. Under optimized
      assay conditions, AN can be determined in the concentration range from 1 fgmL(-1)
      to 100 pgmL(-1) with a detection limit of 0.5 fgmL(-1). The cross-reactivities of
      the anti-AN antibody to seven structurally related compounds were below 15%.
      Environmental water samples were successfully analyzed, showing a good accuracy
      and suitability to analyze AN in field samples. Recovery was between 93.3% and
      120.0% and would be acceptable for use in an on-site field test to provide rapid,
      semiquantitative, and reliable test results for making environmental decisions.

PMID- 19166735
TI  - Detection and quantification of phenolic compounds in olive oil by high
      resolution 1H nuclear magnetic resonance spectroscopy.
AB  - High resolution (1)H NMR spectroscopy has been employed as a versatile and rapid
      method to analyze the polar fraction of extra virgin olive oils containing
      various classes of phenolic compounds. The strategy for identification of
      phenolic compounds is based on the NMR chemical shifts of a large number of model
      compounds assigned by using two-dimensional (2D) NMR spectroscopy. Furthermore,
      2D NMR was applied to phenolic extracts in an attempt to discover additional
      phenolic compounds. The (1)H NMR methodology was successful in detecting simple
      phenols, such as p-coumaric acid, vanillic acid, homovanillyl alcohol, vanillin,
      free tyrosol, and free hydroxytyrosol, the flavonols apigenin and luteolin, the
      lignans (+) pinoresinol, (+) 1-acetoxypinoresinol and syringaresinol, two isomers
      of the aldehydic form of oleuropein and ligstroside, the dialdehydic form of
      oleuropein and ligstroside lacking a carboxymethyl group, and finally total
      hydroxytyrosol and total tyrosol reflecting the total amounts of free and
      esterified hydroxytyrol and tyrosol, respectively. The absolute amount of each
      phenolic constituent was determined in the polar fraction by using anhydrous
      1,3,5-triazine as an internal standard.

PMID- 19166736
TI  - Analysis of EU priority polycyclic aromatic hydrocarbons in food supplements
      using high performance liquid chromatography coupled to an ultraviolet, diode
      array or fluorescence detector.
AB  - High performance liquid chromatography coupled to an ultraviolet, diode array or
      fluorescence detector (HPLC/UV-FLD) has been used to set up a method to detect
      the 15(+1) EU priority polycyclic aromatic hydrocarbons (PAHs) in food
      supplements covering the categories of dried plants and plant extracts excluding
      oily products. A mini validation was performed and the following parameters have
      been determined: limit of detection, limit of quantification, precision, recovery
      and linearity. They were in close agreement with quality criteria described in
      the Commission Regulation (EC) No 333/2007 concerning the PAH benzo[a]pyrene in
      foodstuffs, except the not fluorescent cyclopenta[c,d]pyrene for which the UV
      detection leads to a higher limit of detection. Analysis of twenty commercial
      food supplements covering mainly the class of dried plants was performed to
      evaluate their PAHs contamination levels and to test the applicability of the
      method to various plant matrices. Fifty percent of analyzed samples showed
      concentration exceeding 2 microgkg(-1) for one or more PAHs.

PMID- 19166737
TI  - [Abstracts of the SNF (French Neurology Society) 9th annual meeting].

PMID- 19166763
TI  - Healing kinetics of periapical lesions enhanced by the apexum procedure: a
      clinical trial.
AB  - The new Apexum procedure (Apexum Ltd, Or-Yehuda, Israel) is based on a minimally
      invasive removal of periapical chronically inflamed tissues through a root canal
      access. Its goal is to enhance healing kinetics of periapical lesions. This
      clinical study was conducted to explore the safety and efficacy of this
      procedure. The Apexum procedure was applied, as a supplementary step, during
      conventional root canal treatment in 48 teeth with periapical lesions. Safety and
      efficacy were clinically and radiographically assessed and teeth of the Apexum
      treated group were compared with 39 similar teeth treated by the same endodontic
      procedure with no additional intervention. No adverse events occurred in either
      the Apexum-treated or conventional treatment groups. Furthermore, healing
      kinetics was significantly enhanced in the Apexum-treated group (p < 0.005). At 3
      and 6 months, 87% and 95% of the lesions in the Apexum-treated group,
      respectively, presented advanced or complete healing, whereas only 22% and 39% of
      the lesions in the conventional treatment group presented this degree of healing
      at 3 and 6 months, respectively.

PMID- 19166764
TI  - Regenerative endodontic treatment for necrotic immature permanent teeth.
AB  - This retrospective study included 23 necrotic immature permanent teeth treated
      for either short-term (treatment period <3 months) or long-term (treatment period
      >3 months) using conservative endodontic procedures with 2.5% NaOCl irrigations
      without instrumentation but with Ca(OH)(2) paste medication. For seven teeth
      treated short-term, the gutta-percha points were filled onto an artificial
      barrier of mineral trioxide aggregate (MTA). For 16 teeth treated long-term, the
      gutta-percha points, amalgam, or MTA were filled onto the Ca(OH)(2)-induced hard
      tissue barrier in the root canal. We found that all apical lesions showed
      complete regression in 3 to 21 (mean, 8) months after initial treatment. All
      necrotic immature permanent teeth achieved a nearly normal root development 10 to
      29 (mean, 16) months after initial treatment. We conclude that immature permanent
      teeth with pulp necrosis and apical pathosis can still achieve continued root
      development after proper short-term or long-term regenerative endodontic
      treatment procedures.

PMID- 19166765
TI  - A comparison of the anesthetic efficacy of articaine and lidocaine in patients
      with irreversible pulpitis.
AB  - The purpose of the present study was to compare the anesthetic efficacy of 4%
      articaine with 1:100,000 epinephrine with that of 2% lidocaine with 1:100,000
      epinephrine during pulpectomy in patients with irreversible pulpitis in
      mandibular posterior teeth. Forty volunteers, patients with irreversible pulpitis
      admitted to the Emergency Center of the School of Dentistry at the University of
      Sao Paulo, randomly received a conventional inferior alveolar nerve block
      containing 3.6 mL of either 4% articaine with 1:100,000 epinephrine or 2%
      lidocaine with 1:100,000 epinephrine. During the subsequent pulpectomy, we
      recorded the patients' subjective assessments of lip anesthesia, the
      absence/presence of pulpal anesthesia through electric pulp stimulation, and the
      absence/presence of pain through a verbal analogue scale. All tested patients
      reported lip anesthesia after the application of either inferior alveolar nerve
      block. Regarding pulpal anesthesia success as measured with the pulp tester, the
      lidocaine solution had a higher success rate (70%) than the articaine solution
      (65%). For patients reporting none or mild pain during pulpectomy, the success
      rate of the articaine solution (65%) was higher than that of the lidocaine
      solution (45%). Yet, none of the observed differences between articaine and
      lidocaine were statistically significant. Apparently, therefore, both local
      anesthetic solutions had similar effects on the patients with irreversible
      pulpitis in mandibular posterior teeth. Neither of the solutions, however,
      resulted in an effective pain control during irreversible pulpitis treatments.

PMID- 19166766
TI  - New bacterial compositions in root-filled teeth with periradicular lesions.
AB  - The aim of this study was to isolate and detect microorganisms of root-filled
      teeth associated with periradicular lesions. Specimens were sampled from patients
      undergoing root canal retreatment. The bacteria were characterized by morphologic
      and biochemical analysis and by 16S rRNA gene sequencing. Microorganisms were
      detected in 10 of 18 teeth. The majority of positive samples revealed a mixed
      culture of 2-8 species. In 2 teeth Enterococcus faecalis was the only detected
      species. For the first time Vagococcus fluvialis was detected in root canals.
      Solobacterium moorei and Fusobacterium nucleatum were the most prevalent species.
      Presence of F. nucleatum was associated with the presence of S. moorei in 5 of 7
      cases. In all teeth with Parvimonas micra and Dialister invisus, F. nucleatum and
      S. moorei were found. Moreover, members of additional different genera were
      detected delivering bacterial compositions that have been not described yet.

PMID- 19166767
TI  - Radiographic investigation of frequency and degree of canal curvatures in Chinese
      mandibular permanent incisors.
AB  - Accurate knowledge of root canal curvature is a critical factor in successful
      root canal procedures. The objective of this study was to determine the degree of
      root canal curvature and the frequency of curvature identified in different
      radiographic views in permanent incisors from a Chinese population. The curvature
      of canals from 299 permanent mandibular incisors was investigated by measuring
      the angle, the radius of curvature, and the length of the curved part of the
      canals. These measurements were taken by inserting size 10 K-files into the
      canals and taking radiographs of the tooth-file assembly from both facial and
      proximal views by using a standardized parallel technique. All radiographs were
      analyzed with a computerized digital image processing system. Statistical
      analysis was performed with analysis of variance test at alpha = .05. Of the 299
      teeth examined, 252 (84.3%) were curved, and 125 (41.8%) of the teeth had
      secondary curvature. Curvature was most frequently detected in the proximal views
      rather than in the facial lingual views (P < .05). The highest curvature among
      all samples tested was 44 degrees primary curvature and 36 degrees secondary
      curvature. The maximum and minimum radii of curvature for the sample set were
      54.61 and 1.55 mm, respectively. The mean value of the radius of secondary
      curvature seen in proximal views was significantly less than that of the primary
      ones (P < .05). The length of the curved parts of canals measured maximum and
      minimum values of 14 and 0.33 mm, respectively. It is suggested that the canal
      curvature can start at either the middle third or apical third of the tooth.

PMID- 19166768
TI  - Consistency of apex locator function: a clinical study.
AB  - The consistency of apex locators was determined by calculating the dysfunction
      frequency. Electronic working length (EWL) was determined in 507 patients
      requiring endodontic treatment. Different clinical parameters were recorded
      including tooth vitality, presence of obliteration, and metallic restoration. Two
      apex locators were used (Root ZX [Morita, Tokyo, Japan] and Raypex5 [VDW, Munich,
      Germany]). Apex locator performance was considered "consistent" when the scale
      bars were stable and moved only in correspondence to the movement of file in the
      root canal. A working length radiograph with files set to the EWL was performed.
      EWL were considered "acceptable" when the file tip was located 0 to 2 mm short of
      the radiographic apex. The function of apex locators was consistent in 85% of the
      patients (429/507 [99% confidence interval, 80-88]). The inconsistent
      measurements were strongly associated with partially or totally obliterated root
      canals (p < 0.0001). Radiographically, 97% of consistent measurements were
      "acceptable."

PMID- 19166769
TI  - Herpesviruses in abscesses and cellulitis of endodontic origin.
AB  - Acute apical abscesses and cellulitis are severe endodontic diseases caused by
      opportunistic bacteria with possible coinfection with latent herpesviruses. The
      objectives of this study are to identify herpesviruses, including human
      cytomegalovirus (HCMV), Epstein-Barr virus (EBV), herpes simplex virus-1 (HSV-1),
      and Varicella zoster virus (VZV) in patients (n = 31) presenting with acute
      apical abscesses and cellulitis of endodontic origin. Primary and nested
      polymerase chain reaction (PCR) was conducted using virus-specific primers and
      DNA isolated from cell-free abscess fluid. From patients exhibiting concurrent
      spontaneous pain (n = 28), nine abscesses contained HCMV, two abscesses contained
      EBV, one abscess contained HSV-1, and no abscesses contained VZV. Control PCR
      using genomic or recombinant templates showed detection limits to a single
      genomic copy of HCMV, 100 genomic copies for EBV, and 1 to 10 copies for HSV-1
      with no cross-amplification between herpesviral DNA targets. Nested PCR was
      required for detection of herpesviral DNA in the abscess specimens, indicating
      that these viruses were present in low copy number. Filtration of abscess
      specimens and virus transfer experiments using human fibroblastic MRC-5 cells
      confirmed the presence of HCMV particles in several abscess specimens. We
      conclude that herpesviruses are present but not required for the development of
      acute apical abscesses and cellulitis of endodontic origin.

PMID- 19166770
TI  - Relationship between postendodontic pain, tooth diagnostic factors, and apical
      patency.
AB  - This study compares the incidence, degree, and length of postoperative pain in
      300 endodontically treated teeth, with and without apical patency, in relation to
      some diagnostic factors (vitality, presence of preoperative pain, group, and
      mandible of treated tooth). Of the questionnaires received back, apical patency
      was maintained during shaping procedures with a #10 K-file in one group (n = 115)
      and not in the other (n = 121). There was significantly less postendodontic pain
      when apical patency was maintained in nonvital teeth. If pain appeared, its
      duration was longer when apical patency was maintained in teeth with previous
      pain or located in the mandible. Maintenance of apical patency does not increase
      the incidence, degree, or duration of postoperative pain when considering all
      variables together.

PMID- 19166771
TI  - Defects in nickel-titanium instruments after clinical use. Part 3: a 4-year
      retrospective study from an undergraduate clinic.
AB  - The purpose of this study was to analyze the incidence and mode of ProFile
      (Dentsply Tulsa Dental, Johnson City, TN) instrument separation during a
      predefined schedule of clinical use by the undergraduate students in a dental
      school over 4 years. A total of 3,706 ProFile instruments discarded from the same
      undergraduate students program between 2003 and 2007 were analyzed. The lateral
      and fracture surfaces of 12 separated instruments were examined by scanning
      electron microscopy, and the location of the fractures was recorded. The overall
      proportion of instrument defects was 1.3%; deformation without fracture occurred
      in 1% and separation in 0.3%. The majority of instrument defects occurred in size
      20 (34/48). The ProFile instruments (10/12) failed mostly because of shear
      stress, whereas only two failed because of fatigue fracture. The results of this
      study indicated that NiTi rotary instrument system was successfully introduced
      into an undergraduate endodontic program. Small size files should be considered
      as single-use, disposable instruments because of the higher possibility of
      torsional deformation.

PMID- 19166772
TI  - Defects in nickel-titanium instruments after clinical use. Part 4: an
      electropolished instrument.
AB  - This study aimed to examine the type and location of defects observed in one
      brand of electropolished nickel-titanium instruments after routine clinical use.
      A total of 414 RaCe instruments with structural deformations, discarded from one
      endodontic clinic during a period of 24 months, were analyzed. The lateral and
      fracture surfaces of those separated instruments were examined by scanning; the
      locations of the fractures were recorded. Of all defective instruments, 388 had
      an area of structural change, and 26 were fractured. The distance from the tip of
      the instrument to the end of the deformed area was significantly longer in .02
      taper instruments than in other tapers (P < 0.01), whereas in .04 instruments the
      distorted area ended closer to the tip (P < 0.05). In 31% of all fractured
      instruments, the fragment was 7-8 mm long, more frequently in .04 taper than in
      others. Most of the fractures were found adjacent to the spiraled sector. Shear
      fracture was diagnosed for 22 (85%) of all those fractured, whereas fatigue
      occurred in only 4 instruments (15%) (P < 0.05). There was a marked increase in
      the amount of defects after the seventh (45.4%) and eighth (100%) use. The
      results of this study indicated that RaCe instruments commonly exhibited
      unwinding defects after repeated use, and the most common cause of failure was
      shear failure.

PMID- 19166773
TI  - The prevalence of three-rooted mandibular permanent first molars in a German
      population.
AB  - The purpose of this retrospective study was to assess the prevalence of three
      rooted mandibular first molars among a German dental school patient population. A
      total of 800 patients' full-mouth periapical radiographs were screened, and, out
      of these, 524 patients possessing at least one mandibular first molar were
      selected. The radiographs of these cases were evaluated under optimal conditions
      using double magnifying glasses. The incidence of three-rooted mandibular first
      molars and the correlation between left- and right-side occurrences and between
      males and females were recorded and analyzed using the chi-square test. A total
      of 1,024 mandibular first molars were evaluated. Left molars comprised 500 teeth
      and right molars 524 teeth. Seven patients were found to have a three-rooted
      mandibular first molar, three females and four males (p = 0.981). The overall
      incidence of patients with three-rooted mandibular first molars was 1.35%. All
      three-rooted molars occurred unilaterally. The prevalence of teeth showing an
      extra root from all teeth examined was 0.68%. The right first molar had an
      incidence of 0.57% and the left molar of 0.80%, respectively (p = 0.953). In
      conclusion, the occurrence of three-rooted mandibular first molars among this
      German population was rare.

PMID- 19166774
TI  - An extract of green tea, epigallocatechin-3-gallate, reduces periapical lesions
      by inhibiting cysteine-rich 61 expression in osteoblasts.
AB  - Recent investigations indicate that epigallocatechin-3-gallate (EGCG), the major
      polyphenol of green tea, has anti-inflammatory properties. This study assessed
      the effect of EGCG on oncostatin M (OSM)-induced synthesis of cysteine-rich 61
      (Cyr61), a potential osteolytic mediator, in MG-63 human osteoblastic cells. The
      therapeutic effect of EGCG in apical periodontitis in rats was also examined.
      Western blot analysis showed that OSM stimulated Cyr61 synthesis in MG-63 in a
      time-dependent manner, whereas EGCG readily attenuated this effect. On the other
      hand, Cyr61 treatment of MG-63 cells induced the release of CCL2, a chemokine
      responsible for macrophage chemotaxis. In a rat model of induced apical
      periodontitis, radiography and histopathology revealed that administration of
      EGCG markedly diminished the severity of periapical lesions. The numbers of Cyr61
      synthesizing osteoblasts and infiltrating macrophages were also decreased. Thus,
      EGCG suppresses the progression of apical periodontitis, possibly by diminishing
      Cyr61 expression in osteoblasts and, subsequently, macrophage chemotaxis into the
      lesions.

PMID- 19166775
TI  - Chlorhexidine gluconate attenuates the ability of lipoteichoic acid from
      Enterococcus faecalis to stimulate toll-like receptor 2.
AB  - Chlorhexidine gluconate (CHX) has been widely used as a canal irrigant or an
      intracanal medicament on account of its antibacterial substantivity. This in
      vitro study aimed to determine if CHX attenuates the inflammatory activity of
      Enterococcus faecalis and its major virulence factor, lipoteichoic acid (LTA). An
      enzyme-linked immunosorbent assay showed that CHX-killed E. faecalis was less
      potent than heat-killed E. faecalis in the production of tumor necrosis factor
      alpha (TNF-alpha) by a murine macrophage cell line, RAW 264.7 (p < 0.05).
      Interestingly, pretreatment of LTA with 2% CHX for 6 hours or with 0.2% CHX for
      24 hours almost eliminated the TNF-alpha inducibility (p < 0.05). Furthermore,
      CHX abrogated the ability of LTA to stimulate Toll-like receptor 2, resulting in
      the attenuated induction of TNF-alpha expression. Collectively, our results
      suggest that CHX can inactivate LTA of E. faecalis leading to the alleviation of
      inflammatory responses induced by E. faecalis and its LTA.

PMID- 19166776
TI  - Immunohistochemical localization of IL-17 in induced rat periapical lesions.
AB  - Interleukin (IL)-17 is a member of a novel family of proinflammatory cytokines
      produced almost exclusively by a newly recognized subclass of activated T cells
      called "Th17" cells. From an endodontic perspective, IL-17 potently regulates
      cells of the innate immune system, serving as an important bridging molecule
      between the adaptive and innate immune systems. The purpose of this study was to
      investigate the immunohistochemical localization of IL-17 during the development
      of periapical lesions in rats. Periapical lesions developed within 28 days after
      mandibular first molar pulp exposure in Sprague-Dawley rats. The animals were
      randomly sacrificed at 0, 7, 14, 21, and 28 days after pulpal exposure. The jaws
      that contained the first molar were obtained and routinely prepared for
      histologic analysis, immunohistochemistry, and enzyme histochemistry. From day 0
      to day 28, the number of IL-17-positive cells and neutrophils ascended and peaked
      on day 28. Osteoclast numbers substantially multiplied from day 0 to day 14 and
      then gradually decreased from day 14 to day 28. In addition, the osteoclast
      decrease contrasted with the increased number of IL-17-positive cells and
      neutrophils. These findings showed that IL-17 could be observed and might
      possibly be involved in the inflammatory response and bone resorption of
      periapical tissues as well as associated with periapical lesion pathogenesis.

PMID- 19166777
TI  - Dentin enhances the antibacterial effect of mineral trioxide aggregate and
      bioaggregate.
AB  - The antimicrobial effectiveness of bioaggregate (BA) and mineral trioxide
      aggregate (MTA) against Enterococcus faecalis was evaluated in vitro. Fresh BA
      and MTA powders, powder from crushed set materials, and pieces of uncrushed set
      cements were suspended in autoclaved water at concentrations of 10-100 mg/mL for
      direct exposure testing. The antimicrobial effect of the cements mixed with equal
      amounts of human dentin powder was also tested. BA and MTA powder were equally
      effective in bacterial elimination and caused a significant decrease in bacterial
      viability within 6 minutes. Powder from crushed set cements was either equally or
      more effective than fresh powders in killing the bacteria. The addition of equal
      amounts of dentin powder to the suspension of either BA or MTA powder (both fresh
      and set) resulted in faster elimination of the bacteria (P < 0.05).

PMID- 19166778
TI  - Contemporary methacrylate resin-based root canal sealers exhibit different
      degrees of ex vivo cytotoxicity when cured in their self-cured mode.
AB  - The cytotoxicity of four methacrylate resin-based sealers was investigated by the
      3-(4,5-dimethyl-thiazoyl)-2,5-diphenyl-tetrazolium bromide assay, which measures
      cell viability by assessing its succinate dehydrogenase activity. The sealers
      were polymerized in the self-cured mode to simulate the setting condition upon
      their extrusion into periradicular tissues. Disks were prepared from EndoREZ
      (Ultradent, South Jordan, UT), RealSeal (SybronEndo, Orange, CA), MetaSEAL
      (Parkell, Farmington, NY), and RealSeal SE (SybronEndo) together with positive
      and negative controls. After setting, they were placed in direct contact with rat
      osteosarcoma (ROS 17/2.8) cells and for 5 succeeding weeks after immersing in
      simulated body fluid (SBF). All sealers exhibited severe toxicity initially (week
      0). EndoREZ and RealSeal remained severely toxic after five cycles of SBF
      immersion. Toxicity of the two self-etching resin-based sealers MetaSEAL and
      RealSeal SE decreased gradually over time. Transmission electron microscopy of
      cells exposed to RealSeal SE showed variable degrees of cell injury that reflect
      its toxicity status. Cells with intact mitochondria were identifiable after the
      sealer became noncytotoxic at week 5.

PMID- 19166779
TI  - Analysis of tissue reactions to methacrylate resin-based, epoxy resin-based, and
      zinc oxide-eugenol endodontic sealers.
AB  - The purpose of this study was to investigate the reaction of the subcutaneous
      connective tissue of rats to methacrylate resin-based sealer (EndoREZ), epoxy
      resin-based sealer (AH Plus), and zinc oxide-eugenol sealer (EndoFill).
      Polyethylene tubes containing the test materials were implanted in 18 rats. After
      7, 30, and 60 days, tissues were collected for biopsy and fixed and processed for
      histologic evaluation. Observations were made of the cellular inflammatory
      component, the fibrous condensation, and the abscess formation. Comparisons
      between groups and times were made with the Friedman and Kruskall-Wallis tests.
      EndoREZ and EndoFill sealers showed a more intense and longer-lasting
      inflammation. With AH Plus, the inflammatory reaction showed a tendency to
      diminish over time. The only group to show a statistically significant reduction
      in inflammation during the 60-day period was the control group. None of the
      materials tested proved to have ideal characteristics for biocompatibility.

PMID- 19166780
TI  - Influence of voxel size in the diagnostic ability of cone beam tomography to
      evaluate simulated external root resorption.
AB  - This study assessed in vitro the diagnostic ability of cone beam computed
      tomography (CBCT) scans with different voxel resolutions in the detection of
      simulated external root resorption (ERR). For that purpose, 59 teeth were viewed
      through iCAT tomography (Imaging Sciences International, Inc, Hatfield, PA)
      following three protocols in which the variation was the voxel resolution (0.4,
      0.3, and 0.2mm). A calibrated examiner blinded to the protocol assessed the
      images through the i-CAT View software (Imaging Sciences International, Inc). The
      chi-square statistical analysis did not show associations between voxel
      resolution, section plane, size of cavity, and radicular third. Sensitivity and
      specificity values were similar. However, likelihood ratio values of 6.4 for a
      0.4-mm voxel, 16 for a 0.3-mm voxel, and 12 for a 0.2-mm voxel were found. It was
      concluded that CBCT is a reliable method for the investigation of simulated ERR,
      and a 0.3-mm voxel appeared to be the best protocol, associating good diagnostic
      performance with lower X-ray exposure.

PMID- 19166781
TI  - The ability of different nickel-titanium rotary instruments to induce dentinal
      damage during canal preparation.
AB  - The purpose of this study was to compare the incidence of dentinal defects
      (fractures and craze lines) after canal preparation with different nickel
      titanium rotary files. Two hundred sixty mandibular premolars were selected.
      Forty teeth were left unprepared (n = 40). The other teeth were prepared either
      with manual Flexofiles (n = 20) or with different rotary files systems: ProTaper
      (Dentsply-Maillefer, Ballaigues, Switzerland), ProFile (Dentsply-Maillefer),
      SystemGT (Dentsply-Maillefer), or S-ApeX (FKG Dentaire, La Chaux-de-Fonds,
      Switzerland) (n = 50 each). Roots were then sectioned 3, 6, and 9 mm from the
      apex and observed under a microscope. The presence of dentinal defects was noted.
      There was a significant difference in the appearance of defects between the
      groups (p < 0.05). No defects were found in the unprepared roots and those
      prepared with hand files and S-ApeX. ProTaper, ProFile, and GT preparations
      resulted in dentinal defects in 16%, 8%, and 4% of teeth, respectively. Some
      endodontic preparation methods might damage the root and induce dentinal defects.

PMID- 19166782
TI  - Properties of an accelerated mineral trioxide aggregate-like root-end filling
      material.
AB  - The purpose of the study was to examine the physicochemical properties of mineral
      trioxide aggregate (MTA)-like cements prepared from SiO(2), CaO, and Al(2)O(3) as
      matrices, and ZnO, MgO, and Fe(2)O(3) as additives. The MTA-like cements showed a
      significantly (p < 0.05) faster setting time (<14 minutes) than MTA when mixed
      with water, although there was a significant decrease (p < 0.05) in diametral
      tensile strength, ranging from 0.9 to 3.1 MPa in comparison to MTA (4.4 MPa). The
      addition of ZnO, MgO, and Fe(2)O(3) to the MTA-like cement led to a significantly
      (p < 0.05) higher strength than MTA-like cement without additives. The pH values
      of the MTA-like cements were changed from an initial 11 to a high of 13, similar
      to the results of MTA. Future characterization of the examined MTA-like cement
      with shortened setting time is needed before it is considered a viable candidate
      for dental root-end-filling applications.

PMID- 19166783
TI  - Comparison of mineral trioxide aggregate's composition with Portland cements and
      a new endodontic cement.
AB  - The aim of this study was to compare the compositions of mineral trioxide
      aggregates (MTAs), Portland cements (PCs), and a new endodontic cement (NEC). Our
      study also investigated the surface characteristics of MTA and NEC root-end
      fillings when immersed in normal saline. For part I, we prepared samples of 9
      brands of MTAs, PCs, and NEC. The materials were imaged and analyzed by scanning
      electron microscopy (SEM) and energy dispersive x-ray analysis (EDXA). In part
      II, 3-mm-deep root-end preparations were filled with MTA or NEC and stored in
      normal saline for 1 week. Samples were imaged and analyzed by SEM and electron
      probe microanalysis (EPMA). EDXA investigations revealed differences in the
      dominant compounds of NEC, PCs, and MTAs. The major components of MTA and PC are
      the same except for bismuth. The most significant difference was the presence of
      higher concentrations of Fe (minor element) in gray MTA and PC when compared with
      white ones. EPMA results revealed remarkably different elements in MTA compared
      with surrounding dentin, whereas in the NEC group the distribution patterns of
      calcium, phosphorous, and oxygen were comparable. NEC differs chemically from
      MTAs and PCs and demonstrates comparable surface composition with adjacent dentin
      as a root-end filling material.

PMID- 19166784
TI  - Bond strength of Epiphany sealer prepared with resinous solvent.
AB  - This study evaluated in vitro the bond strength of Epiphany sealer prepared with
      resinous solvent of Epiphany system (Thinning resin) by using a push-out test.
      Forty maxillary canines were sectioned transversally below the cementoenamel
      junction to provide 4-mm-thick dentin disks that were centered in aluminum rings
      and embedded in acrylic resin. Root canals were prepared with tapered diamond
      bur. Intraradicular dentin was treated with 1% NaOCl for 30 minutes, 17%
      ethylenediaminetetraacetic acid for 5 minutes, and flushed with distilled water
      for 1 minute. The specimens were randomly distributed into 4 groups (n = 10)
      according to the filling material: GI, Epiphany without photoactivation; GII,
      Epiphany prepared with solvent without photoactivation; GIII, Epiphany followed
      by photoactivation; and GIV, Epiphany prepared with solvent followed by
      photoactivation. After the setting time, the specimens were submitted to the push
      out test. The highest mean value (14.91 +/- 2.82 MPa) was obtained with Epiphany
      prepared with solvent followed by photoactivation (GIV), which was statistically
      different (P < .01) from the other groups. Groups I (8.15 +/- 2.47 MPa), II (9.46
      +/- 2.38 MPa), and III (9.80 +/- 2.51 MPa) had inferior bond strength values and
      were statistically similar among themselves (P > .01). The resinous solvent of
      Epiphany system increased the bond strength of Epiphany sealer to dentin walls
      when followed by photoactivation.

PMID- 19166785
TI  - A mineral trioxide aggregate sealer stimulated mineralization.
AB  - The aim of this study was to evaluate the rat subcutaneous tissue response to
      implanted polyethylene tubes filled with Endo-CPM-Sealer (Portland Cement
      Modified Sealer) (EGEO S.R.L., Buenos Aires, Argentina) compared with Sealapex
      (SybronEndo, Glendora, CA) and Angelus MTA (Angelus, Londrina, Brazil). These
      materials were placed in polyethylene and dentin tubes and implanted into dorsal
      connective tissue of Wistar rats for 7, 15, 30, 60, and 90 days. The specimens
      were prepared to be stained with hematoxylin and eosin or Von Kossa or not
      stained for polarized light. Qualitative and quantitative evaluations of the
      reaction were performed. Both materials caused mild to moderate reactions at 7
      days that decreased with time. The response was similar to the control on the
      30th day with Endo-CPM-Sealer and Angelus MTA and on the 60th day with Sealapex.
      Mineralization and granulations birefringent to the polarized light were observed
      with all materials. It was possible to conclude that Endo-CPM-Sealer was
      biocompatible and stimulated mineralization.

PMID- 19166786
TI  - Apical quality and adaptation of Resilon, EndoREZ, and Guttaflow root canal
      fillings in combination with a noncompaction technique.
AB  - The objective of this study was to compare the quality of Guttaflow
      (Coltene/Whaledent, Langenau, Germany), Resilon/Epiphany (Jeneric/Pentron,
      Kusterdingen, Germany), and EndoREZ (Ultradent Products, Inc, South Jordan, UT)
      root canal fillings. Thirty single-rooted teeth were randomly assigned to three
      groups: Resilon/Epiphany, EndoREZ, and Guttaflow. After radiography of the root
      canal fillings, the roots were sectioned horizontally at the level of 2 mm and 4
      mm from the apex. The area of voids and adaptation to canal walls and points were
      evaluated using light microscopy and calculated through a computer program. The
      radiographs showed no significant differences between the materials (p > 0.05,
      Mann-Whitney U test). Evaluation of cross-sections revealed sealer adaptation
      >99% to the root canals and >98% to the points. Resilon/Epiphany had
      significantly higher values at 98.8% (standard deviation [SD] = 3.9%) than
      EndoREZ at 98.7% (SD = 1.1%), and Guttaflow at 98.5 (SD = 2.1%) (p < 0.05, Mann
      Whitney U test). The absolute difference compared with Resilon/Epiphany was at
      0.84% (0.44%-1.76%) for EndoREZ and at 1.08% for Guttaflow (0.00%-2.08%) (95%
      confidence interval, Hodges-Lehman). This outcome indicated an effective apical
      obturation using any of the three materials in combination with a noncompaction
      technique.

PMID- 19166787
TI  - Ultrasonic chemical vapor deposition-coated tip versus high- and low-speed
      carbide burs for apicoectomy: time required for resection and scanning electron
      microscopy analysis of the root-end surfaces.
AB  - This study compared ultrasonic chemical vapor deposition (CVD)-coated tip
      (CVDentus #8.1117-1; Clorovale Diamantes Ind. e Com. Ltda Epp, Sao Jose dos
      Campos, SP, Brazil) versus high-speed (#FG700L) and low-speed (#699) carbide burs
      for apicoectomy, evaluating the time required for resection and analyzing the
      root-end surfaces by scanning electron microscopy. Thirty extracted human
      premolars had the canals instrumented and obturated and were randomly assigned to
      3 groups (n = 10), according to the instrument used for root-end resection. The
      time required for resection of the apical 2 mm of each root was recorded. The
      resected apical segments were dried, sputter coated with gold, and examined with
      a scanning electron microscope at x350 magnification. A four-point (0-3) scoring
      system was used to evaluate the apical surface smoothness. The results were
      analyzed statistically by the Kruskal-Wallis test, and two-by-two comparisons
      analyses were performed using the Miller test. The significance level was set at
      5%. Root-end resection with the high-speed bur was significantly faster (p <
      0.05) compared with the low-speed bur and CVD tip. The carbide burs produced
      significantly smoother root-end surfaces than the CVD tip (p < 0.05). The low
      speed bur produced the smoothest root-end surfaces, whereas the roughest and most
      irregular root ends (p < 0.05) were obtained with the CVD tip. However, no
      statistically significant difference (p > 0.05) was found between the high- and
      low-speed burs regarding the surface roughness of the resected root ends (p >
      0.05). In conclusion, under the tested conditions, ultrasonic root-end resection
      took a longer time and resulted in rougher surfaces compared with the use of
      carbide burs at both high and low speed.

PMID- 19166788
TI  - An application framework of three-dimensional reconstruction and measurement for
      endodontic research.
AB  - The purpose of this study was to customize an application framework by using the
      MeVisLab image processing and visualization platform for three-dimensional
      reconstruction and assessment of tooth and root canal morphology. One maxillary
      first molar was scanned before and after preparation with ProTaper by using micro
      computed tomography. With a customized application framework based on MeVisLab,
      internal and external anatomy was reconstructed. Furthermore, the dimensions of
      root canal and radicular dentin were quantified, and effects of canal preparation
      were assessed. Finally, a virtual preparation with risk analysis was performed to
      simulate the removal of a broken instrument. This application framework provided
      an economical platform and met current requirements of endodontic research. The
      broad-based use of high-quality free software and the resulting exchange of
      experience might help to improve the quality of endodontic research with micro
      computed tomography.

PMID- 19166789
TI  - Effects of dentin bonding agents on the cell cycle of fibroblasts.
AB  - The aim of this study was to evaluate the effects of 3 dentin bonding agents on
      cell survival and proliferation and on cell cycle progression of cultured cells.
      The experiments were performed on RPC-C2A and L929 cells. Specimens of the 3
      dentin bonding agents (Clearfil Tri-S, AdheSE, and XP BOND) were placed in
      culture medium, and the extraction media were applied to cells as experimental
      material. The effect of the bonding materials on cell survival and proliferation
      was assessed by a modified sulforhodamine B staining assay, and the effect on DNA
      synthesis was assessed by bromodeoxyuridine uptake. Flow cytometry was used for
      cell cycle analysis. Cell viability and proliferation decreased in a dose
      dependent manner after exposure of cells to the tested materials. XP BOND
      expressed the highest activity of all tested bonding agents (P < .05). The self
      etch bonding agents tested did not produce any significant effects on cell cycle
      distribution. However, exposure of cells to the total-etch agent XP BOND induced
      a G(2)-phase arrest in both cell lines, and this effect was more evident in L929
      cells than in RPC-C2A cells.

PMID- 19166790
TI  - Time-dependent decalcifying effects of endodontic irrigants with antibacterial
      properties.
AB  - The aim of this study was to investigate the extent of calcium ion (Ca(2+))
      removal on root dentin after treatment with 1.25% NaOCl, 2.5% NaOCl, 5.25% NaOCl,
      2% chlorhexidine (CHX), 2% iodine potassium iodide (IKI), and MTAD in 3 immersion
      time periods. Extracted human mandibular premolars were bisected longitudinally,
      and the root halves (n = 70) were isolated with nail varnish, leaving the root
      canal exposed. The specimens were immersed in the test solutions, during which
      the amount of Ca(2+) release into the solutions was determined at 5, 10, and 15
      minutes by flame photometry. The decalcifying effect of 5%, 2.5%, and 1.25% NaOCl
      and 2% IKI significantly increased within time (P < .05), with 5% NaOCl
      extracting the greatest amount of Ca(2+) at all treatment times. For 2% CHX and
      distilled water, a significant increase in the amount of Ca(2+) extraction from
      root dentin was only evident at 10 minutes (P < .05) and did not change at 15
      minute readings. Between the 5- to 10-minute and 10- to 15-minute intervals, the
      greatest amount of increase in the rate of Ca(2+) extraction from root dentin was
      observed in the 2.5% NaOCl group. At 15 minutes, 2% CHX and distilled water
      showed the least amount of change. Among the test solutions, MTAD extracted the
      least amount of Ca(2+) at 5 minutes.

PMID- 19166792
TI  - Osteonecrosis related to intraosseous anesthesia: report of a case.
AB  - Intraosseous anesthesia is an effective and increasingly used technique with few
      reported complications. The technique uses a specialized drill to perforate the
      osseous cortex where local anesthetic can then be deposited to anesthetize teeth.
      It has been reported that separation of the perforation drills from their plastic
      bases can occur because of the friction generated during osseous perforation.
      Prolonged rotation of the perforator drills in the bone can also cause excessive
      heat, which can lead to bone necrosis. This report describes a case of focal
      osteonecrosis subsequent to intraosseous anesthesia and discusses possible
      etiologies of this sequela.

PMID- 19166791
TI  - Particle size and shape of calcium hydroxide.
AB  - The aim of this study was to examine the particle length, width, perimeter, and
      aspect ratio of calcium hydroxide powder using a flow particle image analyzer
      (FPIA). Five sample groups each with 10 mg of calcium hydroxide were mixed with
      15 mL of alcohol and sonicated. Digital images of the particle samples were taken
      using the FPIA and analyzed with a one-way analysis of variance. The overall
      averages +/- standard deviation among the five groups for particle length
      (microm), width (microm), perimeter (microm), and aspect ratio were 2.255 +/-
      1.994, 1.620 +/- 1.464, 6.699 +/- 5.598, and 0.737 +/- 0.149, respectively. No
      statistical significance was observed among the groups for all parameters. When
      the total of 46,818 particles from all five groups were classified into the five
      length categories of 0.5-microm increments, there were significant differences in
      width, perimeter, and aspect ratio (all p values <0.0001). In conclusion, calcium
      hydroxide particles have a size and shape that may allow direct penetration into
      open dentin tubules.

PMID- 19166793
TI  - Use of mineral trioxide aggregate in the treatment of horizontal root fractures
      with a 5-year follow-up: report of a case.
AB  - Root fractures are those that involve dentin, cementum, and the pulp. They occur
      more frequently in children than adults. This case report describes the treatment
      and 5-year follow-up of two maxillary central incisors with horizontal root
      fractures using mineral trioxide aggregate and the application of intracoronal
      bleaching of the discolored tooth.

PMID- 19166794
TI  - Identifying latent autoimmune diabetes in adults in Korea: the role of C-peptide
      and metabolic syndrome.
AB  - We aimed to establish the prevalence and characteristics of latent autoimmune
      diabetes in adults (LADA) and compare it with type 2 diabetes in 1370 Korean
      patients. The prevalence of LADA was 5.1%. Low C-peptide level and absence of
      metabolic syndrome were variables independently associated with the diagnosis of
      LADA.

PMID- 19166795
TI  - Quiz page. Final diagnosis unilateral urinary obstruction in a man with
      peripheral vascular disease.

PMID- 19166796
TI  - Is it worth correcting hyperparathyroidism if hyperphosphatemia and hypocalcemia
      worsen? A cinacalcet story.

PMID- 19166797
TI  - Dietary protein restriction in CKD: the debate continues.

PMID- 19166798
TI  - Is angiotensin-converting enzyme inhibitor and angiotensin receptor blocker
      combination therapy better than monotherapy and safe in patients with CKD?

PMID- 19166800
TI  - Dual blockade of the renin-angiotensin system for cardiorenal protection: an
      update.
AB  - The renin-angiotensin system (RAS) has an important role in hypertension and the
      continuum of cardiovascular and kidney disease. The inhibition of this system,
      either with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin
      receptor blocker (ARB), has been shown to be beneficial for cardiorenal
      protection. Dual blockade with an ACE inhibitor and ARB may have additional
      benefits due to the more complete inhibition of the system. Most published
      trials, including recent large studies and meta-analyses, have reported either
      limited or no additional benefit. Dual-blockade therapy seems to have some
      benefit on proteinuria and blood pressure reduction, and on morbidity and
      mortality in patients with heart failure, compared with monotherapy. The major
      issue arising from these published trials and meta-analyses is the increased
      frequency of dual therapy discontinuation and adverse effects on kidney function.
      There is a lack of hard end-point data for renal outcomes and long-term safety
      data in most published trials. Until the results of ongoing trials become
      available and as further safety data emerge, a wise approach would be to withhold
      use of ACE inhibitor and ARB combination therapy in general practice. When used
      in selected conditions, patients need to be closely monitored.

PMID- 19166799
TI  - Prevalence and awareness of CKD among African Americans: the Jackson Heart Study.
AB  - BACKGROUND: Chronic kidney disease (CKD) leads to end-stage renal disease and is
      a growing epidemic throughout the world. In the United States, African Americans
      have an incidence of end-stage renal disease 4 times that of whites. STUDY
      DESIGN: Cross-sectional to examine the prevalence and awareness of CKD in African
      Americans. SETTING & PARTICIPANTS: Observational cohort in the Jackson Heart
      Study (JHS). PREDICTOR: CKD was defined as an estimated glomerular filtration
      rate less than 60 mL/min/1.73 m(2), the presence of albuminuria, or dialysis
      therapy. OUTCOMES & MEASUREMENTS: Data from the JHS were analyzed. Medical
      history, including disease awareness and drug therapy, anthropometric
      measurements, and serum and urine samples, were obtained from JHS participants at
      the baseline visit. Associations between CKD prevalence and awareness and
      selected demographic, socioeconomic, health care access, and disease status
      parameters were assessed by using logistic regression models. RESULTS: The
      prevalence of CKD in the JHS was 20%; CKD awareness was only 15.8%. Older
      participants had a greater prevalence, but also were more aware of CKD.
      Hypertension, diabetes, cardiovascular disease, hypercholesterolemia,
      hypertriglyceridemia, increasing age and waist circumference, and being single or
      less physically active were associated with CKD. Only advancing CKD stage was
      associated with awareness. LIMITATIONS: Cross-sectional assessment, single urine
      measurement. CONCLUSIONS: The JHS has a high prevalence and low awareness of CKD,
      especially in those with less severe disease status. This emphasizes the need for
      earlier diagnosis and increased education of health care providers and the
      general population.

PMID- 19166801
TI  - The promise of pentoxifylline and interference with the renin-angiotensin system
      in diabetic nephropathy.

PMID- 19166803
TI  - Effect of fish oil on vitamin D absorption.

PMID- 19166804
TI  - Percutaneous transesophageal gastrotubing for a feeding disorder in a patient
      receiving peritoneal dialysis.

PMID- 19166805
TI  - The understanding of infectious diseases mechanisms has been and continues to be
      a priority at the Institut Pasteur, which in 2008 celebrated its 120th
      anniversary.

PMID- 19166806
TI  - Hierarchical band-target entropy minimization curve resolution and Pearson VII
      curve-fitting analysis of cellular protein infrared imaging spectra.
AB  - A soft-modeling multivariate numerical approach that combines self-modeling curve
      resolution (SMCR) and mixed Lorentzian-Gaussian curve fitting was successfully
      implemented for the first time to elucidate spatially and spectroscopically
      resolved spectral information from infrared imaging data of oral mucosa cells. A
      novel variant form of the robust band-target entropy minimization (BTEM) SMCR
      technique, coined as hierarchical BTEM (hBTEM), was introduced to first cluster
      similar cellular infrared spectra using the unsupervised hierarchical leader
      follower cluster analysis (LFCA) and subsequently apply BTEM to clustered subsets
      of data to reconstruct three protein secondary structure (PSS) pure component
      spectra-alpha-helix, beta-sheet, and ambiguous structures-that associate with
      spatially differentiated regions of the cell infrared image. The Pearson VII
      curve-fitting procedure, which approximates a mixed Lorentzian-Gaussian model for
      spectral band shape, was used to optimally curve fit the resolved amide I and II
      bands of various hBTEM reconstructed PSS pure component spectra. The optimized
      Pearson VII band-shape parameters and peak center positions serve as means to
      characterize amide bands of PSS spectra found in various cell locations and for
      approximating their actual amide I/II intensity ratios. The new hBTEM methodology
      can also be potentially applied to vibrational spectroscopic datasets with
      dynamic or spatial variations arising from chemical reactions, physical
      perturbations, pathological states, and the like.

PMID- 19166807
TI  - A signal-amplified electrochemical immunosensor for aflatoxin B(1) determination
      in rice.
AB  - A sensitive and simple electrochemical immunosensor based on enzymatic silver
      deposition amplification was constructed for the detection of aflatoxin B(1)
      (AFB(1)) in rice. The immunosensor was based on an indirect competitive format
      between free AFB(1) and aflatoxin B(1)-bovine serum albumin (AFB(1)-BSA)
      conjugate immobilized on the electrode surface for binding to a fixed amount of
      anti-AFB(1) antibody. Then the alkaline phosphatase (ALP)-labeled anti-mouse
      immunoglobulin G (IgG) secondary antibody was bound to the electrode surface
      through reaction with primary antibody. Finally, ALP catalyzed the substrate,
      ascorbic acid 2-phosphate, into ascorbic acid that reduced silver ions in
      solution to metal silver deposited onto the electrode surface. Linear sweep
      voltammetry was carried out to quantify the metal silver, which indirectly
      reflected the amount of the analyte. The experimental parameters, such as the
      dilution ratio of antibody and the concentration of AFB(1)-BSA conjugate, have
      been evaluated and optimized. At the optimal conditions, the working range of the
      electrochemical immunosensor was from 0.1 to 10 ng/ml with a detection limit of
      0.06 ng/ml. Good recoveries were obtained for the detection of spiked rice
      samples. So, the proposed method in this article could find a good use for
      screening AFB(1) in real samples.

PMID- 19166808
TI  - Biosensor based on the biocatalysis of microperoxidase-11 in nanocomposite
      material of multiwalled carbon nanotubes/room temperature ionic liquid for
      amperometric determination of hydrogen peroxide.
AB  - A novel nanocomposite material of multiwalled carbon nanotubes (MWCNTs) and room
      temperature ionic liquid (RTIL) N-butylpyridinium hexafluorophosphate (BPPF6) was
      explored and used to construct a novel microperoxidase-11 (MP-11) biosensor for
      the determination of hydrogen peroxide (H2O2). Cyclic voltammetry (CV) and
      differential pulse voltammetry (DPV) were used to characterize the performance of
      the biosensor. Under the optimized experimental conditions, H2O2 could be
      detected in a linear calibration range of 0.5 to 7.0 x 10(-7)mol L(-1) with a
      correlation coefficient of 0.9949 (n=9) and a detection limit of 3.8 x 10(-9) mol
      L(-1) at 3 sigma. The modified electrodes displayed excellent electrochemical
      response, high sensitivity, long-term stability, and good bioactivity and
      selectivity.

PMID- 19166809
TI  - CacyBP/SIP binds ERK1/2 and affects transcriptional activity of Elk-1.
AB  - In this work we showed for the first time that mouse CacyBP/SIP interacts with
      extracellular signal regulated kinases 1 and 2 (ERK1/2). We also established that
      a calcium binding protein, S100A6, competes for this interaction. Moreover, the
      E217K mutant of CacyBP/SIP does not bind significantly to ERK1/2 although it
      retains the ability to interact with S100A6. Molecular modeling shows that the
      E217K mutation in the 189-219 CacyBP/SIP fragment markedly changes its
      electrostatic potential, suggesting that the binding with ERK1/2 might have an
      electrostatic character. We also demonstrate that CacyBP/SIP-ERK1/2 interaction
      inhibits phosphorylation of the Elk-1 transcription factor in vitro and in the
      nuclear fraction of NB2a cells. Altogether, our data suggest that the binding of
      CacyBP/SIP with ERK1/2 might regulate Elk-1 phosphorylation/transcriptional
      activity and that S100A6 might further modulate this effect via Ca(2+)-dependent
      interaction with CacyBP/SIP and competition with ERK1/2.

PMID- 19166810
TI  - Mechanism and significance of specific proteolytic cleavage of Reelin.
AB  - Reelin is a secreted glycoprotein essential for normal brain development and
      function. In the extracellular milieu, Reelin is subject to specific cleavage at
      two (N-t and C-t) sites. The N-t cleavage of Reelin is implicated in psychiatric
      and Alzheimer's diseases, but the molecular mechanism and physiological
      significance of this cleavage are not completely understood. Particularly,
      whether the N-t cleavage affects the signaling activity of Reelin remains
      controversial. Here, we show that the protease in charge of the N-t cleavage of
      Reelin requires the activity of certain proprotein convertase family for
      maturation and has strong affinity for heparin. By taking advantage of these
      observations, we for the first time succeeded in obtaining "Uncleaved" and
      "Completely Cleaved" Reelin proteins. The N-t cleavage splits Reelin into two
      distinct fragments and virtually abolishes its signaling activity. These findings
      provide an important biochemical basis for the function of Reelin proteolysis in
      brain development and function.

PMID- 19166811
TI  - Generation and immunogenicity of Japanese encephalitis virus envelope protein
      expressed in transgenic rice.
AB  - Transgenic plants have become attractive as bioreactors to produce heterologous
      proteins that can be developed as edible vaccines. In the present study,
      transgenic rice expressing the envelope protein (E) of Japanese encephalitis
      virus (JEV), under the control of a dual cauliflower mosaic virus (CaMV 35S)
      promoter, was generated by Agrobacterium-mediated transformation. Southern blot,
      Northern blot, Western blot and ELISA analyses confirmed that the E gene was
      integrated into transgenic rice and was expressed in the leaves at levels of 1.1
      1.9 microg/mg of total soluble protein. After intraperitoneal immunization of
      mice with crude protein extracts from transgenic rice plants, JEV-specific
      neutralizing antibody could be detected. Moreover, E-specific mucosal immune
      responses could be detected in mice after oral immunization with protein extracts
      from transgenic rice plants. These results show the potential of using a
      transgenic rice-based expression system as an alternative bioreactor for JEV
      subunit vaccine.

PMID- 19166812
TI  - The actin-capping protein CapG localizes to microtubule-dependent organelles
      during the cell cycle.
AB  - Extensive cross-talk between the actin and the microtubule cytoskeletons has been
      reported. Especially in mitosis, processes dependent on actin- and microtubule
      based structures alternate and regulate each other in a complex cascade leading
      to division into two daughter cells. Here, we have studied the subcellular
      localization of the filamentous actin-capping protein CapG. Fluorescence
      microscopy of endogenous CapG and EGFP-tagged CapG revealed CapG localization at
      the mother centriole in interphase, the mitotic spindle in mitosis and the
      midbody ring in abscission. Surprisingly, nucleoporin Nup62, an interaction
      partner of CapG, also localized to the midbody ring at the end of abscission and
      colocalized with CapG. We propose a role for the actin-binding protein CapG as a
      mediator of cross-talk between the actin cytoskeleton and microtubule-based
      organelles that regulate cell division.

PMID- 19166813
TI  - Hydrogen sulfide from adipose tissue is a novel insulin resistance regulator.
AB  - Recent data suggested that endogenous hydrogen sulfide (H(2)S) contributes to the
      pathogenesis of diabetes. Here, we identified that cystathionine gamma lyase
      (CSE) was expressed in adipose tissue in rats and endogenously generated H(2)S.
      The CSE/H(2)S system exists in both rat adipocytes and pre-adipocytes. This
      system was up-regulated with aging, although a high level of glucose down
      regulated the system in a concentration- and time-dependent manner. H(2)S
      inhibited the basal and insulin-stimulated glucose uptake of mature adipocytes,
      whereas administration of CSE inhibitors enhanced the glucose uptake of
      adipocytes. The PI3K but not K(ATP) channel pathway is involved in the inhibitory
      effect of H(2)S on glucose uptake. Finally, in fructose-induced diabetes in rats,
      we confirmed the up-regulated CSE/H(2)S system in adipose tissue, which was
      negatively correlated with glucose uptake in this tissue. Our findings suggest
      that H(2)S might be a novel insulin resistance regulator.

PMID- 19166814
TI  - A Maurer's cleft-associated Plasmodium falciparum membrane-associated histidine
      rich protein peptide specifically interacts with the erythrocyte membrane.
AB  - The membrane-associated histidine-rich protein-1 (MAHRP-1) is a Maurer's cleft
      resident molecule that has been recently described as an important protein for
      the trafficking of PfEMP-1 to infected erythrocyte membrane, a major virulence
      factor. We have studied the specific interactions between 20-mer-long synthetic
      peptides spanning the complete MAHRP-1 sequence and erythrocytes. A high-activity
      binding peptide (HABP) with saturable binding to a 46-kDa erythrocyte membrane
      protein was identified and its binding was affected by chymotrypsin treatment.
      Random coil and alpha-helical features were found in the HABP's structure. Our
      results suggest that MAHRP-1 specifically interacts with erythrocyte membrane
      through a 20-mer-long amino acid region, raising questions about this region's
      potential as a therapeutic target against malaria.

PMID- 19166815
TI  - Interplay between in vitro acetylation and phosphorylation of tailless HMGB1
      protein.
AB  - The postsynthetic acetylation of HMGB1 protein and its truncated form affects
      significantly its properties as "architectural" factor - recognition of bent DNA
      and bending of short DNA fragments. We created mutants at the target sites
      (lysines 2 and 81) in the tailless HMGB1 modified by the histone
      acetyltransferase CBP. The results show that there is no preferential site for
      the enzymatic activity of CBP and both lysine moieties are modified
      independently. Our findings for the first time demonstrate the link between the
      acetylation and phosphorylation of HMGB1DeltaC in vitro. The PKC phosphorylation
      prior to acetylation inhibits the CBP activity 40-60% for the truncated form and
      its mutants. The effect of the CBP acetylation on the phosphorylation level turns
      out to be much more prominent. In the case of HMGB1DeltaC modified at Lys 2 and
      Lys 81 prior to PKC treatment background phosphorylation is detected. If only one
      of the lysines is modified the inhibitory effect decreases.

PMID- 19166816
TI  - Analyzing indirect secondary electron contrast of unstained bacteriophage T4
      based on SEM images and Monte Carlo simulations.
AB  - The indirect secondary electron contrast (ISEC) condition of the scanning
      electron microscopy (SEM) produces high contrast detection with minimal damage of
      unstained biological samples mounted under a thin carbon film. The high contrast
      image is created by a secondary electron signal produced under the carbon film by
      a low acceleration voltage. Here, we show that ISEC condition is clearly able to
      detect unstained bacteriophage T4 under a thin carbon film (10-15 nm) by using
      high-resolution field emission (FE) SEM. The results show that FE-SEM provides
      higher resolution than thermionic emission SEM. Furthermore, we investigated the
      scattered electron area within the carbon film under ISEC conditions using Monte
      Carlo simulation. The simulations indicated that the image resolution difference
      is related to the scattering width in the carbon film and the electron beam spot
      size. Using ISEC conditions on unstained virus samples would produce low
      electronic damage, because the electron beam does not directly irradiate the
      sample. In addition to the routine analysis, this method can be utilized for
      structural analysis of various biological samples like viruses, bacteria, and
      protein complexes.

PMID- 19166817
TI  - Inhibitors of insulin-like growth factor-1 receptor tyrosine kinase are
      preferentially cytotoxic to nutrient-deprived pancreatic cancer cells.
AB  - Chronic deprivation of nutrients is rare in normal tissues, however large areas
      of tumor are nutrient-starved and hypoxic due to a disorganized vascular system.
      Some cancers show an inherent ability to tolerate severe growth conditions.
      Therefore, we screened chemical compounds to identify cytotoxic agents that
      function preferentially in nutrient-deprived conditions. We found that AG1024, a
      specific inhibitor of insulin-like growth factor-1 receptor tyrosine kinase (IGF
      1R), showed preferential cytotoxicity to human pancreatic cancer cells in
      nutrient-deprived conditions relative to cells in nutrient-sufficient conditions.
      The cytotoxicity of I-OMe-AG538 (another specific inhibitor of IGF-1R kinase) was
      also enhanced in nutrient-deprived cells. In addition, AG1024 and I-OMe-AG538
      potently inhibited IGF-1R activation to nutrient-deprived cells. In contrast,
      conventional chemotherapeutic drugs, as well as inhibitors of PDGFR and EGFR
      kinases, elicited weak cytotoxicity. These data indicate that nutrient-deprived
      human pancreatic cancer cells have increased sensitivity to inhibition of IGF-1R
      activation. IGF-1R inhibitors offer a promising strategy for anticancer
      therapeutic approaches that are oriented toward tumor microenvironment.

PMID- 19166818
TI  - Crystal structure of SCCA1 and insight about the interaction with JNK1.
AB  - Squamous cell carcinoma antigen 1 (SCCA1), which belongs to serine proteinase
      inhibitor (serpin) superfamily, inhibits papain-like cysteine proteinase.
      Recently, it has been reported that SCCA1 acts not only as a proteinase inhibitor
      but also as an inhibitor of UV-induced apoptosis via suppression of the activity
      of c-Jun NH(2)-terminal kinase (JNK1). The present study determined the crystal
      structure of SCCA1, suggesting that the reactive center loop (RCL) of SCCA1, a
      recognition site of proteinase, is very flexible and located away form the main
      body of SCCA1. We show that the inhibitory effect of SCCA1 on the kinase activity
      of JNK1 is lost when the RCL was truncated. Furthermore, we found that a mutant
      protein created by replacing one amino acid in RCL maintain the suppressive
      activity to JNK1, whereas the inhibitory effect to proteinase is obviously
      decreased.

PMID- 19166819
TI  - NMR structure of the Wnt modulator protein Sclerostin.
AB  - Sclerostin has been identified as a negative regulator of bone growth. Initially
      it was considered that Sclerostin performs its regulatory function via acting as
      a modulator of bone morphogenetic proteins (BMPs) similar to known examples such
      as Noggin, Chordin, and members of the DAN family. Recent findings, however, show
      that Sclerostin interferes with the Wnt signaling pathway due to binding to the
      Wnt co-receptor LRP5 thereby modulating bone growth. As Sclerostin is exclusively
      produced by osteocytes located in bones, neutralization of its bone-inhibiting
      functions makes it a highly interesting target for an osteoanabolic therapeutic
      approach in diseases characterized by bone loss, such as osteoporosis. Despite
      the huge interest in Sclerostin inhibitors the molecular basis of its function
      and its interaction with components of the Wnt signaling cascade has remained
      unclear. Here, we present the NMR structure of murine Sclerostin providing the
      first insights how Sclerostin might bind to LRP5.

PMID- 19166820
TI  - Enhanced radiosensitivity and radiation-induced apoptosis in glioma CD133
      positive cells by knockdown of SirT1 expression.
AB  - CD133-expressing glioma cells play a critical role in tumor recovery after
      treatment and are resistant to radiotherapy. Herein, we demonstrated that
      glioblastoma-derived CD133-positive cells (GBM-CD133(+)) are capable of self
      renewal and express high levels of embryonic stem cell genes and SirT1 compared
      to GBM-CD133(-) cells. To evaluate the role of SirT1 in GBM-CD133(+), we used a
      lentiviral vector expressing shRNA to knock-down SirT1 expression (sh-SirT1) in
      GBM-CD133(+). Silencing of SirT1 significantly enhanced the sensitivity of GBM
      CD133(+) to radiation and increased the level of radiation-mediated apoptosis.
      Importantly, knock-down of SirT1 increased the effectiveness of radiotherapy in
      the inhibition of tumor growth in nude mice transplanted with GBM-CD133(+).
      Kaplan-Meier survival analysis indicated that the mean survival rate of GBM
      CD133(+) mice treated with radiotherapy was significantly improved by Sh-SirT1 as
      well. In sum, these results suggest that SirT1 is a potential target for
      increasing the sensitivity of GBM and glioblastoma-associated cancer stem cells
      to radiotherapy.

PMID- 19166823
TI  - Amyloid beta induces cellular relocalization and production of agrin and glypican
      1.
AB  - The major component of senile plaques and vascular amyloid in Alzheimer's disease
      (AD) brains is the amyloid beta protein (Abeta). Besides Abeta, several other
      proteins have been identified in these lesions, in particular heparan sulfate
      proteoglycans (HSPG). However, it is still unclear, what causes the excessive
      accumulation of HSPG in AD brains. Therefore, we investigated if Abeta may
      influence production and expression of two major Abeta-associated HSPG species,
      agrin and glypican-1. When human brain pericytes (HBP) were cultured in the
      presence of Abeta, protein and mRNA expression of both agrin and glypican-1 were
      increased and more radioactive sulfate was incorporated in the glycosaminoglycan
      fraction of Abeta-treated HBP. Furthermore, after Abeta treatment, these HSPG
      were found in association with the amyloid fibrils attached to the cell membrane,
      in contrast to the intracellular agrin and glypican-1 staining observed in
      untreated cells. We conclude that Abeta can modulate the cellular expression of
      agrin and glypican-1, which may contribute to the accumulation of these HSPG in
      AD lesions.

PMID- 19166821
TI  - Leptin regulates tau phosphorylation and amyloid through AMPK in neuronal cells.
AB  - Leptin, which serves as a lipid-modulating hormone to control metabolic energy
      availability, is decreased in Alzheimer's disease (AD) patients, and serum levels
      are inversely correlated to severity of dementia. We have previously described
      the effects of leptin in reducing amyloid beta protein both in vitro and in vivo,
      and tau phosphorylation in vitro. Herein, we systematically investigated the
      signaling pathways activated by leptin, leading to these molecular endpoints, to
      better understand its mechanism of action. Inhibition of amyloid beta production
      and tau phosphorylation in leptin-treated human and/or rat neuronal cultures were
      both dependent on activation of AMP-activated protein kinase (AMPK). Direct
      stimulation of AMPK with the cell-permeable activator, 5-aminoimidazole-4
      carboxyamide ribonucleoside (AICAR), replicated leptin's effects and conversely,
      Compound C, an inhibitor of AMPK, blocked leptin's action. The data implicate
      that AMPK is a key regulator of both AD-related pathways.

PMID- 19166822
TI  - The selective aryl hydrocarbon receptor modulator 6-methyl-1,3,8
      trichlorodibenzofuran inhibits prostate tumor metastasis in TRAMP mice.
AB  - The aryl hydrocarbon receptor (AhR) is a basic-helix-loop-helix transcription
      factor that binds halogenated aromatic hydrocarbons, polycyclic aromatic
      hydrocarbons, and endogenous compounds. We previously reported that AhR null
      (Ahr(-/-)) transgenic adenocarcinoma of the mouse prostate (TRAMP) mice on a
      C57BL/6J background develop prostate tumors with much greater frequency than AhR
      wild-type (Ahr(+/+)) TRAMP mice, suggesting that the AhR has tumor suppressor
      properties. Because AhR signaling pathway inactivation increased susceptibility
      to prostate tumorigenesis, we tested the hypothesis that a selective AhR
      modulator (SAhRM), 6-methyl-1,3,8-trichlorodibenzofuran (6-MCDF), can protect
      against prostate tumorigenesis. TRAMP mice on the standard C57BL/6JxFVB genetic
      background were fed 0, 10, or 40mg 6-MCDF/kg diet beginning at 8 weeks of age.
      Tumor incidence, pelvic lymph node metastasis, and serum vascular endothelial
      growth factor (VEGF) concentrations were determined at 140 days of age. Prostate
      tumor incidence and size were not significantly reduced in mice fed 6-MCDF.
      However, the frequency of pelvic lymph node metastasis was reduced fivefold in
      mice fed the 40mg 6-MCDF/kg diet. Serum VEGF concentrations were also reduced by
      6-MCDF treatment, particularly in mice without prostate tumors, and 6-MCDF was
      shown to act directly on cultured prostates to inhibit VEGF secretion. Together,
      these results suggest that 6-MCDF inhibits metastasis, in part, by inhibiting
      prostatic VEGF production prior to tumor formation. This is the first report that
      6-MCDF can confer protection against prostate cancer in vivo.

PMID- 19166824
TI  - Identification of N-acetyl Proline-Glycine-Proline (acPGP) in human serum of
      adults and newborns by liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: N-acetyl Proline-Glycine-Proline (acPGP) is a novel neutrophil
      chemoattractant. However, no studies have been reported to identify the presence
      of acPGP in human serum. The purpose of our study was to establish a method for
      measuring acPGP, and to determine whether acPGP is present in human serum.
      METHODS: Serum samples were obtained from 22 healthy adults and 26 term and
      preterm newborns. For the sensitive analysis of acPGP, we utilized liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) with a multiple reaction
      monitoring (MRM) positive ion mode. RESULTS: The major product ions of acPGP
      ([M+H](+) ion, m/z 312) appeared at 112 and 140. The MRM (transition: m/z
      312/112) chromatogram in human serum showed a single peak with the same retention
      time as that of authentic acPGP. The calibration curve of authentic acPGP was
      linear, and our quantitative results indicated high precision. The mean serum
      acPGP levels in adults and newborns were 6.3 and 18.7 pg/ml, respectively. In
      newborns, lower birth weight infants had significantly higher serum acPGP levels.
      CONCLUSIONS: We established a method for the quantification of serum acPGP using
      LC-MS/MS, and this paper provides the first evidence for the presence of acPGP in
      human serum of adults and newborns.

PMID- 19166825
TI  - Assessing the quality of Bionime self-monitoring blood glucose system Rightest
      GM110: a critical evaluation of interference and ambient circumstances.
AB  - BACKGROUND: The key issue in preventing chronic diabetic complications is to
      maintain near-normoglycemia. Analytical evaluation of Bionime self-monitoring
      blood glucose (SMBG) Rightest GM110 was carried out in this study. METHODS: The
      evaluation was executed according to the Standards for Reporting Diagnostic
      Accuracy (STARD) and the Clinical and Laboratory Standards Institute (CLSI). The
      evaluation procedure mainly focused on analytical performance. The accuracy tests
      included hematocrit, interferants, temperature, humidity, altitude and clinical
      evaluations. RESULTS: Good linearity response (R(2)>0.99) and satisfactory
      precision (CVs: 1.1-2.8%) were observed in glucose concentrations of 0.6-30.5
      mmol/l. In hematocrit test, the Rightest GM110 was suitable for use in sample
      containing hematocrit in the range of 30-55%. Interfering test indicated that
      almost all substances tested were insignificant, with bias <10% in medium- and
      hyper-glycemia samples. Satisfactory stability was also found under various
      ambient circumstances, with bias within +/-10%. In clinical trials, values within
      the acceptable zone (A+B) were 100% and values within zone A exceed 95% in error
      grid analysis. CONCLUSIONS: The Bionime Rightest GM110 is reliable to display
      accurate glucose concentrations in specimens with irresistible interfering
      factors.

PMID- 19166826
TI  - Homocysteine level and metabolism in ischemic stroke in the population of
      Northern Poland.
AB  - OBJECTIVES: In this study we analyzed the occurrence of ischemic brain stroke in
      Northern Poland in regard to risk factors. DESIGN AND METHODS: 131 ischemic
      stroke patients and 64 controls were studied. Analyzed risk factors included
      conventional risk factors, total plasma homocysteine level and polymorphisms of
      the main enzymes of homocysteine metabolism-methylenetetrahydrofolate reductase
      (polymorphisms C677T and A1298C) and cystathionine beta synthase (polymorphism
      T833C). RESULTS: We confirmed the occurrence of a number of conventional risk
      factors in ischemic stroke. We found that hyperhomocysteinemia is an independent
      risk factor (p=0.0001). Plasma homocysteine correlated inversely with plasma
      vitamin B(6). We also found a relationship between C677T polymorphism type and
      hyperhomocysteinemia (p=0.0266). CONCLUSIONS: The occurrence of studied
      polymorphisms in the population of northern Poland was higher than reported
      previously for similar populations. However, none of the studied genetic factors
      were found to be significant risk factors in ischemic brain stroke.

PMID- 19166827
TI  - Predictors for cardiovascular morbidity and overall mortality in Tunisian ESRD
      patients: a six year prospective study.
AB  - OBJECTIVES: The study was aimed to test the predictive value of several potential
      cardiovascular factors and markers for non fatal cardiovascular events (CVE) and
      overall mortality in Tunisian patients with renal failure. SUBJECTS AND METHODS:
      One hundred and fifteen renal failure patients were followed-up from 2000 to
      2006. At enrollment, each patient underwent clinical examination and blood
      collection for analysis of lipid parameters, albumin, C reactive protein (CRP),
      parathyroid hormone (PTH), homocysteine and hemoglobin. Multivariate Cox
      regression models were applied to identify the predictors for non fatal CVE and
      overall mortality. RESULTS: During the follow up, seventeen patients were lost.
      Among the 98 remaining patients, 29 presented a non fatal CVE (21.5%) and 15 were
      deceased (11.1%). In univariate analyses, non fatal CVE were more frequent in
      smokers and in patients with high PTH concentrations and low HDL levels.
      Moreover, low albumin concentrations were univariately associated with overall
      mortality. In the multivariate analysis, non fatal CVE was significantly and
      independently associated with age [hazard ratio (95% confidence interval), 1.04
      (1.01-1.08); p=0.028] and the upper quartile of PTH concentrations [2.68 (1.24
      5.81); p=0.013]. Overall mortality was independently predicted by the bottom
      quartile of albumin concentrations [5.62 (2.02-15.6); p=0.001] and the upper
      quartile of CRP concentrations [3.20 (1.14-8.79); p=0.027]. CONCLUSION: Advanced
      age and high PTH levels are the main predictors of CVE, whereas low albumin and
      high CRP concentrations are the independent predictors of death in Tunisian renal
      patients. A better control of these factors would greatly increase the patient's
      survival rates.

PMID- 19166828
TI  - Elevated transrenal DNA (cell-free urine DNA) in patients with urinary tract
      infection compared to healthy controls.
AB  - OBJECTIVE: To study whether levels of transrenal DNA (Tr-DNA) are influenced by
      the presence of urinary tract infections (UTI). METHODS: Tr-DNA concentrations
      were measured in 124 donors and 55 patients with UTI. Two methods for DNA
      extraction were compared. RESULTS: UTI patients showed higher concentrations than
      the donors (normal range: 0-147 GE/mL). QIAamp MiniElute Virus Spin Kit was more
      efficient than QIAamp DNA Blood Mini Kit. CONCLUSION: Increased concentrations of
      Tr-DNA urine DNA are shown in presence of UTI.

PMID- 19166831
TI  - Sarcomeric-alpha-actinin defective in vinculin-binding causes Z-line expansion
      and nemaline-like body formation in cultured chick myotubes.
AB  - The Z-line in each striated muscle has a precisely defined width that corresponds
      to muscle fiber type, and it can enlarge several fold in nemaline myopathy. To
      explore the mechanism(s) underlying Z-line width and structure maintenance, a
      series of sarcomeric-alpha-actinin mutants tagged with myc-epitope was
      transfected into cultured chick myotubes. By double-staining transfected myotubes
      with myc and myofibrillar protein antibodies, we found that alpha-actinin mutants
      with deletion of the region from the beginning of the fourth spectrin repeat to
      the start of the EF-hands resulted in expansion of Z-line width, often displayed
      a doublet staining pattern, and resulted in formation of nemaline-like bodies in
      older myotubes under fluorescence microscope. Yeast-two hybridization analysis
      demonstrated that this region was involved in vinculin binding, and for vinculin
      to bind alpha-actinin, residues 1-116 and 258-323 were required. Hence, we have
      defined a critical region of s-alpha-actinin that affects the width and integrity
      of the Z-line. This region is at least involved in the interaction with vinculin.

PMID- 19166830
TI  - Par-1 and Tau regulate the anterior-posterior gradient of microtubules in
      Drosophila oocytes.
AB  - The formation of an anterior-posterior (AP) gradient of microtubules in
      Drosophila oocytes is essential for specification of the AP axis. Proper
      microtubule organization in the oocyte requires the function of serine/threonine
      kinase Par-1. The N1S isoform of Par-1 is enriched at the posterior cortex of the
      oocyte from stage 7 of oogenesis. Here we report that posterior restriction of
      Par-1 (N1S) kinase activity is critical for microtubule AP gradient formation.
      Egg chambers with excessive and ectopic Par-1 (N1S) kinase activity in the
      germline cells display phenotypes similar to those of egg chambers treated with
      the microtubule-depolymerizing drug colcemid: depolymerization of microtubules in
      the oocyte and disruption of oocyte nucleus localization. A phosphorylation
      target of Par-1, the microtubule-associated protein Tau, is also involved in
      oocyte polarity formation, and overexpression of Tau alleviates the phenotypes
      caused by ectopic Par-1 (N1S) kinase activity, suggesting that Par-1 regulates
      oocyte polarity at least partly through Tau. Our findings reveal that maintaining
      proper levels of Par-1 at correct position in the oocyte is key to oocyte
      polarity formation and that the conserved role of Par-1 and Tau is crucial for
      the establishment of an AP gradient of microtubules and for AP axis
      specification.

PMID- 19166829
TI  - Shox2 is essential for the differentiation of cardiac pacemaker cells by
      repressing Nkx2-5.
AB  - The pacemaker is composed of specialized cardiomyocytes located within the
      sinoatrial node (SAN), and is responsible for originating and regulating the
      heart beat. Recent advances towards understanding the SAN development have been
      made on the genetic control and gene interaction within this structure. Here we
      report that the Shox2 homeodomain transcription factor is restrictedly expressed
      in the sinus venosus region including the SAN and the sinus valves during
      embryonic heart development. Shox2 null mutation results in embryonic lethality
      due to cardiovascular defects, including an abnormal low heart beat rate
      (bradycardia) and severely hypoplastic SAN and sinus valves attributed to a
      significantly decreased level of cell proliferation. Genetically, the lack of
      Tbx3 and Hcn4 expression, along with ectopic activation of Nppa, Cx40, and Nkx2-5
      in the Shox2(-/-) SAN region, indicates a failure in SAN differentiation.
      Furthermore, Shox2 overexpression in Xenopus embryos results in extensive
      repression of Nkx2-5 in the developing heart, leading to a reduced cardiac field
      and aberrant heart formation. Reporter gene expression assays provide additional
      evidence for the repression of Nkx2-5 promoter activity by Shox2. Taken together
      our results demonstrate that Shox2 plays an essential role in the SAN and
      pacemaker development by controlling a genetic cascade through the repression of
      Nkx2-5.

PMID- 19166832
TI  - Histological protection by cilnidipine, a dual L/N-type Ca(2+) channel blocker,
      against neurotoxicity induced by ischemia-reperfusion in rat retina.
AB  - Although a blockade or lack of N-type Ca(2+) channels has been reported to
      suppress neuronal injury induced by ischemia-reperfusion in several animal
      models, information is still limited regarding the neuroprotective effects of a
      dual L/N-type Ca(2+) channel blocker, cilnidipine. We histologically examined the
      effects of cilnidipine on neuronal injury induced by ischemia-reperfusion,
      intravitreous N-methyl-D-aspartate (NMDA) (200nmol/eye) and intravitreous NOC12
      (400nmol/eye), an nitric oxide donor, in the rat retina, and compared its effects
      with those of omega-conotoxin MV IIA, an N-type Ca(2+) channel blocker and
      amlodipine, an L-type Ca(2+) channel blocker. Morphometric evaluation at 7 days
      after ischemia-reperfusion showed that treatment with cilnidipine (100microg/kg,
      i.v. or 0.5pmol/eye, intravitreous injection) prior to ischemia dramatically
      reduced the retinal damage. Treatment with omega-conotoxin MV IIA before ischemia
      (0.1pmol/eye, intravitreous injection) significantly reduced the retinal damage.
      However, amlodipine (30-100microg/kg, i.v. or 0.1-1pmol/eye, intravitreous
      injection) did not show any protective effects. Treatment with cilnidipine
      (100microg/kg, i.v.) reduced the retinal damage induced by intravitreous NMDA,
      but not NOC12. These results suggest that cilnidipine reduces Ca(2+) influx via N
      type Ca(2+) channels after NMDA receptors activation and then protects neurons
      against ischemia-reperfusion injury in the rat retina in vivo. Cilnidipine may be
      useful as a therapeutic drug against retinal diseases which cause neuronal cell
      death, such as glaucoma and central retinal vessel occlusion.

PMID- 19166834
TI  - Cinnamon polyphenols attenuate cell swelling and mitochondrial dysfunction
      following oxygen-glucose deprivation in glial cells.
AB  - Astrocyte swelling is an integral component of cytotoxic brain edema in ischemic
      injury. While mechanisms underlying astrocyte swelling are likely multifactorial,
      oxidative stress and mitochondrial dysfunction are hypothesized to contribute to
      such swelling. We investigated the protective effects of cinnamon polyphenol
      extract (CPE) that has anti-oxidant and insulin-potentiating effects on cell
      swelling and depolarization of the inner mitochondrial membrane potential
      (DeltaPsi(m)) in ischemic injury. C6 glial cells were subjected to oxygen-glucose
      deprivation (OGD) and cell volume determined using the 3-O-methyl-[3H]-glucose
      method at 90 min after the end of OGD. When compared with controls, OGD increased
      cell volume by 34%. This increase was blocked by CPE or insulin but not by
      blockers of oxidative/nitrosative stress including vitamin E, resveratrol, N
      nitro-L-arginine methyl ester (L-NAME) or uric acid. Mitochondrial dysfunction, a
      key component of ischemic injury, contributes to cell swelling. Changes in
      DeltaPsi(m) were assessed at the end of OGD with tetramethylrhodamine ethyl ester
      (TMRE), a potentiometric dye. OGD induced a 39% decline in DeltaPsi(m) and this
      decline was blocked by CPE as well as insulin. To test the involvement of the
      mitochondrial permeability transition (mPT), we used Cyclosporin A (CsA), an
      immunosuppressant and a blocker of the mPT pore. CsA blocked cell swelling and
      the decline in DeltaPsi(m) but FK506, an immunosuppressant that does not block
      the mPT, did not. Our results show that CPE reduces OGD-induced cell swelling as
      well as the decline in DeltaPsi(m) in cultures and some of its protective effects
      may be through inhibiting the mPT.

PMID- 19166835
TI  - Biomarkers for Parkinson's disease.
AB  - With the advent of systems biological concepts there has been a surge of interest
      in biological factors, or biomarkers that can be measured and which allow the
      identification of individuals at risk. Biomarkers for Parkinson's disease have
      been identified which provide evidence of systemic metabolic dysregulation in
      this disorder. Such biomarkers can be studied in blood, serum and plasma but also
      in CSF and urine, and the study by Hoepken et al. in this issue has even made use
      of skin fibroblasts. The authors report on the induction of alpha-synuclein
      expression and suggest that the expression changes described might potentially
      allow objective PD patient diagnosis in an accessible, peripheral tissue. This
      mini-review aims to provide a broader perspective on PD functional genomics and
      seeks to illustrate in a systems biological context why the findings by Hoepken
      and colleagues are of clinical significance.

PMID- 19166833
TI  - Doublecortin expression in adult cat and primate cerebral cortex relates to
      immature neurons that develop into GABAergic subgroups.
AB  - DCX-immunoreactive (DCX+) cells occur in the piriform cortex in adult mice and
      rats, but also in the neocortex in adult guinea pigs and rabbits. Here we
      describe these cells in adult domestic cats and primates. In cats and rhesus
      monkeys, DCX+ cells existed across the allo- and neocortex, with an overall
      ventrodorsal high to low gradient at a given frontal plane. Labeled cells formed
      a cellular band in layers II and upper III, exhibiting dramatic differences in
      somal size (5-20 microm), shape (unipolar, bipolar, multipolar and irregular),
      neuritic complexity and labeling intensity. Cell clusters were also seen in this
      band, and those in the entorhinal cortex extended into deeper layers as chain
      like structures. Densitometry revealed a parallel decline of the cells across
      regions with age in cats. Besides the cellular band, medium-sized cells with weak
      DCX reactivity resided sparsely in other layers. Throughout the cortex, virtually
      all DCX+ cells co-expressed polysialylated neural cell adhesion molecule. Medium
      to large mature-looking DCX+ cells frequently colocalized with neuron-specific
      nuclear protein and gamma-aminobutyric acid (GABA), and those with a reduced DCX
      expression also partially co-labeled for glutamic acid decarboxylase,
      parvalbumin, calbindin, beta-nicotinamide adenine dinucleotide phosphate
      diaphorase and neuronal nitric oxide synthase. Similar to cats and monkeys, small
      and larger DCX+ cells were detected in surgically removed human frontal and
      temporal cortices. These data suggest that immature neurons persist into
      adulthood in many cortical areas in cats and primates, and that these cells
      appear to undergo development and differentiation to become functional subgroups
      of GABAergic interneurons.

PMID- 19166836
TI  - In vitro priming to direct neuronal fate in adult neural progenitor cells.
AB  - We have previously reported methods that allow for the routine isolation, culture
      and transplantation of multipotent neural progenitor cells (NPCs) derived from
      the adult rat sub-ventricular zone (SVZ). In order to expand these techniques,
      the aim of the current study was to develop an in vitro strategy which can
      "prime" proliferating adult NPCs towards a neuronal fate during their subsequent
      differentiation under standard conditions. Our results show that transient
      exposure to lithium chloride during in vitro proliferation of adult SVZ-derived
      NPCs has the ability to alter differential fate in vitro and increase the
      proportion of cells expressing neuronal markers while at the same time causing a
      reduction in glial progeny. Treatment of adult NPCs with lithium chloride may
      therefore provide a novel mechanism by which adult NPCs can be primed towards a
      specific neuronal fate for cell replacement therapy.

PMID- 19166837
TI  - Simvastatin reduces secondary brain injury caused by cortical contusion in rats:
      possible involvement of TLR4/NF-kappaB pathway.
AB  - Simvastatin, a cholesterol-lowering agent, has demonstrated neuroprotective
      effects against brain injury, but the underlying mechanisms remain unclear. This
      study was undertaken to evaluate the effect of simvastatin on the Toll-like
      receptor 4 (TLR4) and nuclear factor-kappa B (NF-kappaB) related signaling
      pathway and secondary brain injury in rats after traumatic brain injury (TBI).
      Adult male Wistar rats were divided into four groups: (1) Sham group (n=25); (2)
      Sham+vehicle group (n=25); (3) TBI+vehicle group (n=30); and (4) TBI+simvastatin
      group (n=30). Right parietal cortical contusion was made by using a weight
      dropping method. In TBI+simvastatin group, simvastatin was administered orally at
      a dose of 37.5 mg/kg at 1 and 6 h after TBI. Brain samples were extracted at 24 h
      after trauma. As a result, we found that treatment with simvastatin markedly
      inhibited the mRNA and protein expressions of TLR4, NF-kappaB and the downstream
      inflammatory agents, such as interleukin-1beta (IL-1beta), tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6), and intercellular adhesion molecule-1
      (ICAM-1). Administration of simvastatin following TBI significantly ameliorated
      the secondary brain damage, such as cortical apoptosis, brain edema, blood-brain
      barrier (BBB) impairment, and motor deficits. In conclusion, post-TBI simvastatin
      administration may attenuate TLR4/NF-kappaB-mediated inflammatory response in the
      injured rat brain, and this may be one mechanism by which simvastatin improves
      outcome following TBI.

PMID- 19166838
TI  - Altered splicing of Tau in DM1 is different from the foetal splicing process.
AB  - Among the different mechanisms underlying the etiopathogenesis of myotonic
      dystrophy type 1 (DM1), a backward reprogramming to a foetal splicing machinery
      is an interesting hypothesis. To address this possibility, Tau splicing, which is
      regulated during development and modified in DM1, was analyzed. Indeed, a
      preferential expression of the foetal Tau isoform, instead of the six normally
      found, is observed in adult DM1 brains. By using two cell lines, we show here
      that the cis-regulating elements necessary to generate the unique foetal Tau
      isoform are dispensable to reproduce the trans-dominant effect induced by DM1
      mutation on Tau exon 2 inclusion. Our results suggest that the mis-splicing of
      Tau in DM1 is resulting from a disease-associated mechanism.

PMID- 19166839
TI  - Immobility of phycobilins in the thylakoid lumen of a cryptophyte suggests that
      protein diffusion in the lumen is very restricted.
AB  - The thylakoid lumen is an important photosynthetic compartment which is the site
      of key steps in photosynthetic electron transport. The fluidity of the lumen
      could be a major constraint on photosynthetic electron transport rates. We used
      Fluorescence Recovery After Photobleaching in cells of the cryptophyte alga
      Rhodomonas salina to probe the diffusion of phycoerythrin in the lumen and
      chlorophyll complexes in the thylakoid membrane. In neither case was there any
      detectable diffusion over a timescale of several minutes. This indicates very
      restricted phycoerythrin mobility. This may be a general feature of protein
      diffusion in the thylakoid lumen.

PMID- 19166840
TI  - FKBP25, a novel regulator of the p53 pathway, induces the degradation of MDM2 and
      activation of p53.
AB  - The p53 tumour suppressor protein is tightly controlled by the E3 ubiquitin
      ligase, mouse double minute 2 (MDM2), but maintains MDM2 expression as part of a
      negative feedback loop. We have identified the immunophilin, 25kDa FK506-binding
      protein (FKBP25), previously shown to be regulated by p53-mediated repression, as
      an MDM2-interacting partner. We show that FKBP25 stimulates auto-ubiquitylation
      and proteasomal degradation of MDM2, leading to the induction of p53. Depletion
      of FKBP25 by siRNA leads to increased levels of MDM2 and a corresponding
      reduction in p53 and p21 levels. These data are consistent with the idea that
      FKBP25 contributes to regulation of the p53-MDM2 negative feedback loop.

PMID- 19166841
TI  - Cereblon is expressed in the retina and binds to voltage-gated chloride channels.
AB  - The function of the central nervous system depends on the correct regulation of
      ion channels by interacting proteins. Here, we identified cereblon as a new
      interactor of the voltage-gated chloride channel ClC-2. A distal region of the
      ClC-2 C-terminus interacts with the Lon domain of cereblon. Cereblon is expressed
      in several brain regions including the retina. There, we detected cereblon in
      nuclear and synaptic layers and localized the protein in the same subcellular
      region of bipolar cell bodies previously reported to express ClC-2. Our data
      suggest that cereblon might be associated with voltage-gated chloride channels in
      the central nervous system.

PMID- 19166843
TI  - Individual and common inhibitors of coronavirus and picornavirus main proteases.
AB  - Picornaviruses (PV) and coronaviruses (CoV) are positive-stranded RNA viruses
      which infect millions of people worldwide each year, resulting in a wide range of
      clinical outcomes. As reported in this study, using high throughput screening
      against approximately 6800 small molecules, we have identified several novel
      inhibitors of SARS-CoV 3CL(pro) with IC(50) of low microM. Interestingly, one of
      them equally inhibited both 3C(pro) and 3CL(pro) from PV and CoV, respectively.
      Using computer modeling, the structural features of these compounds as individual
      and common protease inhibitors were elucidated to enhance our knowledge for
      developing anti-viral agents against PV and CoV.

PMID- 19166842
TI  - Cell surface sialylation and fucosylation are regulated by the cell recognition
      molecule L1 via PLCgamma and cooperate to modulate embryonic stem cell survival
      and proliferation.
AB  - Cell surface glycosylation patterns are markers of cell type and status. However,
      the mechanisms regulating surface glycosylation patterns remain unknown. Using a
      panel of carbohydrate markers, we have shown that cell surface sialylation and
      fucosylation are upregulated in L1-transfected embryonic stem cells (L1-ESCs).
      Consistently, the mRNA levels of sialyltransferase ST6Gal1 and ST3Gal4, and
      fucosyltransferase FUT9 were significantly increased in L1-transfected ESCs.
      Activation of L1 signaling promoted cell survival and inhibited cell
      proliferation. ShRNAs knocking down FUT9, ST6Gal1 and ST3Gal4 blocked these
      effects. A phospholipase Cgamma (PLCgamma) inhibitor and shRNA reduced ST6Gal1,
      ST3Gal4 and FUT9 mRNA levels in the L1-ESCs. Thus, embryonic stem cell surface
      sialylation and fucosylation are regulated via PLCgamma by L1, with which they
      cooperate to modulate cell survival and proliferation.

PMID- 19166844
TI  - KITENIN increases invasion and migration of mouse squamous cancer cells and
      promotes pulmonary metastasis in a mouse squamous tumor model.
AB  - KAI1 C-terminal interacting tetraspanin (KITENIN) is reported to promote
      metastasis in mouse colon cancer models. We investigated the role of KITENIN on
      the progression of squamous cell carcinoma (SCC). In a preliminary clinical study
      using resected tissues from head and neck SCC patients, KITENIN was highly
      expressed in tumors and metastatic lymph nodes, while KAI1 was more increased in
      adjacent mucosa than in tumor. KITENIN-transfected mouse squamous cancer (SCC
      VII/KITENIN) cells showed significantly higher invasion, migration, and
      proliferation than empty vector-transfected cells. In syngeneic mouse squamous
      tumor models, more increased tumor volume and enhanced lung metastasis were found
      in SCC VII/KITENIN cells-injected mice. Thus, KITENIN increases invasion and
      migration of squamous cancer cells and thereby promotes distant metastasis in
      mouse squamous tumor models.

PMID- 19166845
TI  - Introduction and characterization of a polymerase-dead point mutation into the
      POLK gene in vertebrates.
AB  - The chicken DT40 cell line is widely used for gene knock-outs. We attempted to
      introduce a polymerase-dead point mutation into Polkappa, a polymerase for
      translesion DNA synthesis, taking advantage of the highly efficient targeted
      integration in DT40 cells. The resulting cells (REV3(-/-)POLK(/)(pol-dead))
      proliferated with the same kinetics as the parental REV3(-/-) cells. Though the
      mock-treated REV3(-/-)POLK(/)(mock) cells showed the same sensitivity as the
      parental REV3(-/-) cells to methyl methanesulfonate, the REV3(-/-)POLK(/)(pol
      dead) cells demonstrated the same sensitivity as the REV3(-/-)POLK(/-) double
      knock-out cells. This implies that the presence of the polymerase-dead Polkappa
      does not interfere with other polymerases repairing monoalkylation damage.

PMID- 19166846
TI  - Regulation of the activity and expression of ERK8 by DNA damage.
AB  - We have investigated the agonists that activate transfected extracellular signal
      regulated kinase 8 (ERK8) in cells, and have found that the most potent
      activators are hydrogen peroxide, DNA alkylating and cross-linking agents and the
      poly (ADP-ribose) polymerase inhibitor KU-0058948. The feature shared by all
      these agents is that they lead to the accumulation of single strand breaks in
      DNA, suggesting a role for ERK8 in the response to, or repair of, DNA single
      strand breaks. The DNA alkylating agent MMS also induced the disappearance of
      endogenous ERK8 by a proteasome-dependent mechanism.

PMID- 19166847
TI  - Analysis of the nucleoside triphosphatase, RNA triphosphatase, and unwinding
      activities of the helicase domain of dengue virus NS3 protein.
AB  - The helicase domain of dengue virus NS3 protein (DENV NS3H) contains RNA
      stimulated nucleoside triphosphatase (NTPase), ATPase/helicase, and RNA 5'
      triphosphatase (RTPase) activities that are essential for viral RNA replication
      and capping. Here, we show that DENV NS3H unwinds 3'-tailed duplex with an RNA
      but not a DNA loading strand, and the helicase activity is poorly processive. The
      substrate of the divalent cation-dependent RTPase activity is not restricted to
      viral RNA 5'-terminus, a protruding 5'-terminus made the RNA 5'-triphosphate
      readily accessible to DENV NS3H. DENV NS3H preferentially binds RNA to DNA, and
      the functional interaction with RNA is sensitive to ionic strength.

PMID- 19166848
TI  - Degradation of FAT10 by the 26S proteasome is independent of ubiquitylation but
      relies on NUB1L.
AB  - The ubiquitin-like modifier FAT10 targets proteins for degradation by the
      proteasome, a process accelerated by the UBL-UBA domain protein NEDD8 ultimate
      buster 1-long. Here, we show that FAT10-mediated degradation occurs independently
      of poly-ubiquitylation as purified 26S proteasome readily degraded FAT10
      dihydrofolate reductase (DHFR) but not ubiquitin-DHFR in vitro. Interestingly,
      the 26S proteasome could only degrade FAT10-DHFR when NUB1L was present. Knock
      down of NUB1L attenuated the degradation of FAT10-DHFR in intact cells suggesting
      that NUB1L determines the degradation rate of FAT10-linked proteins. In
      conclusion, our data establish FAT10 as a ubiquitin-independent but NUB1L
      dependent targeting signal for proteasomal degradation.

PMID- 19166849
TI  - Differential regulation of Akt/protein kinase B isoforms during cell cycle
      progression.
AB  - Phosphatidylinositol 3-kinase pathways play key regulatory roles in cell cycle
      progression into S phase. In this study, we demonstrated that Akt1/PKBalpha
      isoform plays an essential role in G(1)/S transition and proliferation. Cells
      lacking Akt1/PKBalpha showed an attenuated proliferation as well as G(1)/S
      transition, whereas cells lacking Akt2/PKBbeta showed normal proliferation and
      G(1)/S transition. The effect of Akt1/PKBalpha on cell proliferation and G(1)/S
      transition was completely abolished by swapping pleckstrin homology (PH) domain
      with that of Akt2/PKBbeta. Finally, full activation of Akt/PKB and cyclin D
      expression was achieved by the Akt1/PKBalpha or chimeric proteins containing the
      PH domain of Akt1/PKBalpha indicating that the PH domain of Akt1/PKBalpha
      provides full kinase activity and is necessary for the G(1)/S transition.

PMID- 19166850
TI  - Oligomeric structure of LOV domains in Arabidopsis phototropin.
AB  - Oligomeric structures of the four LOV domains in Arabidopsis phototropin1 (phot1)
      and 2 (phot2) were studied using crosslinking. Both LOV1 domains of phot1 and
      phot2 form a dimer independently on the light conditions, suggesting that the
      LOV1 domain can be a stable dimerization site of phot in vivo. In contrast, phot1
      LOV2 is in a monomer-dimer equilibrium and phot2-LOV2 exists as a monomer in the
      dark. Blue light-induced a slight increase in the monomer population in phot1
      LOV2, suggesting a possible blue light-inducible dissociation of dimers.
      Furthermore, blue light caused a band shift of the phot2-LOV2 monomer. CD spectra
      revealed the unfolding of helices and the formation of strand structures. Both
      light-induced changes were reversible in the dark.

PMID- 19166851
TI  - Kaiso is a bimodal modulator for Wnt/beta-catenin signaling.
AB  - The Wnt family of secreted ligands plays critical roles during embryonic
      development and tumorigenesis. Here we show that Kaiso, a dual specific DNA
      binding protein, functions as a bimodal regulator of canonical Wnt signaling.
      Loss-of-function analysis of Kaiso abrogated Wnt-mediated reporter activity and
      axis duplication, whereas gain-of-function analysis of Kaiso dose-dependently
      resulted in synergistic and suppressive effects. Our analyses further suggest
      Kaiso can regulate TCF/LEF1-activity for these effects via modulating HDAC1 and
      beta-catenin-complex formation. Our studies together provide insights into why
      Kaiso null mice display resistance to intestinal tumors when crossed onto an
      Apc(Min/+) background.

PMID- 19166852
TI  - Increased -1 ribosomal frameshifting efficiency by yeast prion-like phenotype
      [PSI+].
AB  - Programmed -1 ribosomal frameshifting (-1RF) is usually regulated by a slippery
      sequence and an RNA secondary structure but can be affected by the slippery
      sequence combined with translational perturbation. Dramatic increases of -1RF
      efficiencies arise from the slippery sequences in [PSI+], an epigenetic modifier
      of translation termination fidelity. Curing of [PSI+] abolished such increases of
      -1RF efficiency. Enhanced -1RF frequency at the slippery sequences could be
      another physiological effect induced directly or indirectly by the perturbation
      of the translation process in [PSI+] cells.

PMID- 19166853
TI  - The role of the maturase HydG in [FeFe]-hydrogenase active site synthesis and
      assembly.
AB  - [FeFe]-hydrogenases catalyze the protons/hydrogen interconversion through a
      unique di-iron active site consisting of three CO and two CN ligands, and a non
      protein SCH(2)XCH(2)S (X=N or O) dithiolate bridge. Site assembly requires two
      "Radical-S-adenosylmethionine (SAM or AdoMet)" iron-sulfur enzymes, HydE and
      HydG, and one GTPase, HydF. The sequence homology between HydG and ThiH, a
      Radical-SAM enzyme which cleaves tyrosine into p-cresol and dehydroglycine, and
      the finding of a similar cleavage reaction catalyzed by HydG suggests a mechanism
      for hydrogenase maturation. Here we propose that HydG is specifically involved in
      the synthesis of the dithiolate ligand, with two tyrosine-derived dehydroglycines
      as precursors along with an [FeS] cluster of HydG functioning both as electron
      shuttle and source of the sulfur atoms.

PMID- 19166854
TI  - 14-3-3 Binding to Pim-phosphorylated Ser166 and Ser186 of human Mdm2--Potential
      interplay with the PKB/Akt pathway and p14(ARF).
AB  - Here we show that 14-3-3 proteins bind to Pim kinase-phosphorylated Ser166 and
      Ser186 on the human E3 ubiquitin ligase mouse double minute 2 (Mdm2), but not
      protein kinase B (PKB)/Akt-phosphorylated Ser166 and Ser188. Pim-mediated
      phosphorylation of Ser186 blocks phosphorylation of Ser188 by PKB, indicating
      potential interplay between the Pim and PKB signaling pathways in regulating
      Mdm2. In cells, expression of Pim kinases promoted phosphorylation of Ser166 and
      Ser186, interaction of Mdm2 with endogenous 14-3-3s and p14(ARF), and also
      increased the amount of Mdm2 protein by a mechanism that does not require Pim
      kinase activities. The implications of these findings for regulation of the p53
      pathway, oncogenesis and drug discovery are discussed.

PMID- 19166855
TI  - Burden of digestive diseases in the United States part II: lower gastrointestinal
      diseases.

PMID- 19166856
TI  - Targeting cardiac sympatho-vagal imbalance using gene transfer of nitric oxide
      synthase.
AB  - Heightened sympathetic excitation and diminished parasympathetic suppression of
      heart rate, cardiac contractility and vascular tone are all associated with
      cardiovascular diseases such as hypertension and ischemic heart disease. This
      phenotype often exists before these disease states have been established and is a
      strong correlate of mortality in the population. However, the causal role of the
      autonomic phenotype in the development and maintenance of hypertension and
      myocardial ischemia remains a subject of debate, as are the mechanisms
      responsible for regulating sympathovagal balance. Emerging evidence suggests
      oxidative stress and reactive oxygen species (such as nitric oxide (NO) and
      superoxide) play important roles in the modulation of autonomic balance, but so
      far the most important sites of action of these ubiquitous signaling molecules
      are unclear. In many cases, these mediators have opposing effects in separate
      tissues rendering conventional pharmacological approaches non-efficacious. Novel
      techniques have recently been used to augment these signaling pathways
      experimentally in a targeted fashion to central autonomic nuclei, cardiac
      neurons, and myocytes using gene transfer of NO synthase. This review article
      discusses these recent advances in the understanding of the roles of NO and its
      oxidative metabolites on autonomic imbalance in models of cardiovascular disease.

PMID- 19166857
TI  - Evidence for regulation of mitochondrial function by the L-type Ca2+ channel in
      ventricular myocytes.
AB  - The L-type Ca(2+) channel is responsible for initiating contraction in the heart.
      Mitochondria are responsible for meeting the cellular energy demands and calcium
      is required for the activity of metabolic intermediates. We examined whether
      activation of the L-type Ca(2+) channel alone is sufficient to alter
      mitochondrial function. The channel was activated directly with the
      dihydropyridine agonist BayK(-) or voltage-clamp of the plasma membrane and
      indirectly by depolarization of the membrane with high KCl. Activation of the
      channel increased superoxide production (assessed as changes in dihydroethidium
      fluorescence), NADH production and metabolic activity (assessed as formation of
      formazan from tetrazolium) in a calcium-dependent manner. Activation of the
      channel also increased mitochondrial membrane potential assessed as changes in JC
      1 fluorescence. The response was reversible upon inactivation of the channel
      during voltage-clamp of the plasma membrane and did not appear to require
      calcium. We examined whether the response may be mediated through movement of
      cytoskeletal proteins. Depolymerization of actin or exposing cells to a peptide
      directed against the alpha-interacting domain of the alpha(1C)-subunit of the
      channel (thereby preventing movement of the beta-subunit) attenuated the increase
      in mitochondrial membrane potential. We conclude that activation of the L-type
      Ca(2+) channel can regulate mitochondrial function and the response appears to be
      modulated by movement through the cytoskeleton.

PMID- 19166858
TI  - Molecular and functional characterization of a new potassium conductance in mouse
      ventricular fibroblasts.
AB  - The present work is aimed at identifying and characterizing, at a molecular and
      functional level, new ionic conductances potentially involved in the excitation
      secretion coupling and proliferation of cardiac ventricular fibroblasts. Among
      potassium channel transcripts which were screened by high-throughput real-time
      PCR, SUR2 and Kir6.1 mRNAs were found to be the most abundant in ventricular
      fibroblasts. The corresponding proteins were not detected by western blot
      following 5 days of cell culture, but had appeared at 7 days, increasing with
      extended cell culture duration as the fibroblasts differentiated into
      myofibroblasts. Using the inside-out configuration of the patch-clamp technique,
      single potassium channels could be recorded. These had properties similar to
      those reported for SUR2/Kir6.1 channels, i.e. activation by pinacidil, inhibition
      by glibenclamide and activation by intracellular UDP. As already reported for
      this molecular signature, they were insensitive to intracellular ATP. In the
      whole-cell configuration, these channels have been shown to be responsible for a
      glibenclamide-sensitive macroscopic potassium current which can be activated not
      only by pinacidil, but also by nanomolar concentrations of the sphingolipid
      sphingosine-1-phosphate (S1P). The activation of this current resulted in an
      increase in cell proliferation and a decrease in IL-6 secretion, suggesting it
      has a functional role in situations where S1P increases. Overall, this work
      demonstrates for the first time that SUR2/Kir6.1 channels represent a significant
      potassium conductance in ventricular fibroblasts which may be activated in physio
      pathological conditions and which may impact on fibroblast proliferation and
      function.

PMID- 19166859
TI  - Functional differences between human Cx37 polymorphic hemichannels.
AB  - A polymorphism in the human Cx37 gene (C1019T), resulting in a non-conservative
      amino acid change in the regulatory C-terminus of the Cx37 protein (P319S), has
      been proposed as a prognostic marker for atherosclerosis. We have recently
      demonstrated that Cx37 hemichannels control the initiation of atherosclerotic
      plaque development by regulating ATP-dependent monocyte adhesion in
      atherosclerosis-susceptible apolipoprotein E-deficient mice. In this study, we
      have measured the electrical properties of Cx37 hemichannels (HCs) and gap
      junction channels (GJCs) with voltage-clamp methods. To this end, we have
      transfected hCx37-P319, hCx37-S319 or empty pIRES-eGFP vector cDNA into
      communication-deficient HeLa cells. In clones expressing similar levels of Cx37,
      exposure of single cells to low-Ca(2+) solution induced a voltage-sensitive HC
      current. The analysis yielded a bell-shaped function g(hc)=f(V(m)) (g(hc):
      normalized conductance at steady state; V(m): membrane potential) with a maximum
      around V(m)=-30 mV. The peak g(hc) of Cx37-P319 was 3-fold larger than that of
      Cx37-S319 HCs. Experiments on cell pairs revealed that Cx37-P319 GJCs exhibited a
      1.5-fold larger unitary conductance than Cx37-S319 GJCs. Hence, the larger peak
      g(hc) of the former may reflect a larger conductance of their HCs. Using the same
      clones, we found that Cx37-P319 cells released more ATP and were less adhesive
      than Cx37-S319 cells. The reduction in adhesiveness of Cx37-expressing cells was
      prevented by extracellular apyrase. We conclude that the differences in
      biophysical properties between polymorphic HCs may be responsible for inequality
      in ATP release between Cx37-P319 and Cx37-S319 cells, which results in
      differential cell adhesion.

PMID- 19166860
TI  - Structural studies on the Pseudomonas aeruginosa sialidase-like enzyme PA2794
      suggest substrate and mechanistic variations.
AB  - Pseudomonas aeruginosa encodes an enzyme (PA2794) that is annotated as a
      sialidase (or neuraminidase), as it possesses three bacterial neuraminidase
      repeats that are a signature of nonviral sialidases. A recent report showed that
      when the gene encoding this sialidase is knocked out, this led to a reduction in
      biofilm production in the lungs of mice, and it was suggested that the enzyme
      recognizes pseudaminic acid, a sialic acid analogue that decorates the flagella
      of Pseudomonas, Helicobacter, and Campylobacter species. Here, we present the
      crystal structure of the P. aeruginosa enzyme and show that it adopts a trimeric
      structure, partly held together by an immunoglobulin-like trimerization domain
      that is C-terminal to a classical beta-propeller sialidase domain. The
      recombinant enzyme does not show any sialidase activity with the standard
      fluorogenic sialic-acid-based substrate. The proposed active site contains
      certain conserved features of a sialidase: a nucleophilic tyrosine with its
      associated glutamic acid, and two of the usual three arginines that interact with
      the carboxylic acid group of the substrate, but is missing the first arginine and
      the aspartic acid that acts as an acid/base in all sialidases studied to date. We
      show, by in silico docking, that the active site may accommodate pseudaminic acid
      but not sialic acid and that this is due, in part, to a phenylalanine in the
      hydrophobic pocket that selects for the alternative stereochemistry of
      pseudaminic acid at C5 compared to sialic acid. Mutation of this phenylalanine to
      an alanine converts the enzyme into a sialidase, albeit a poor one, which we
      confirm by kinetics and NMR, and this allowed us to probe the function of other
      amino acids. We propose that a histidine plays the role of the acid/base, whose
      state is altered through a charge-relay system involving a novel His-Tyr-Glu
      triad. The location of this relay system precludes the presence of one of the
      three arginines usually found in a sialidase active site.

PMID- 19166862
TI  - Effects of resveratrol on nucleotide degrading enzymes in streptozotocin-induced
      diabetic rats.
AB  - AIMS: Diabetes mellitus is associated with platelet alterations that may
      contribute to the development of cardiovascular complications. The present study
      investigates the effects of resveratrol (RSV), an important compound with
      cardioprotective activities, on NTPDase, ecto-nucleotide
      pyrophosphatase/phosphodiesterase (E-NPP), 5'-nucleotidase and adenosine
      deaminase (ADA) activities in platelets from streptozotocin (STZ)-induced
      diabetic rats. MAIN METHODS: The animals were divided into six groups (n=8):
      control/saline; control/RSV 10 mg/kg; control/RSV 20 mg/kg; diabetic/saline;
      diabetic/RSV 10 mg/kg; diabetic/RSV 20 mg/kg. RSV was administered during 30 days
      and after this period the blood was collected for enzymatic assay. KEY FINDINGS:
      The results demonstrated that NTPDase, E-NPP and 5'-nucleotidase activities were
      significantly higher in the diabetic/saline group (P<0.05) compared to
      control/saline group. Treatment with RSV significantly increased NTPDase, 5'
      nucleotidase and E-NPP activities in the diabetic/RSV10 and diabetic/RSV20 groups
      (P<0.05) compared to diabetic/saline group. When RSV was administered per se
      there was also an increase in the activities of these enzymes in the
      control/RSV10 and control/RSV20 groups (P<0.05) compared to control/saline group.
      ADA activity was significantly increased in the diabetic/saline group (P<0.05)
      compared to control/saline group. The treatment with RSV prevented this increase
      in the diabetic/RSV10 and diabetic/RSV20 groups. No significant differences in
      ADA activity were observed in the control/RSV10 and control/RSV20 compared to
      control/saline group. SIGNIFICANCE: The present findings demonstrate alterations
      in nucleotide hydrolysis in platelets of STZ-induced diabetic rats and treatment
      with RSV was able to modulate adenine nucleotide hydrolysis, which may be
      important in the control of the platelet coagulant status in diabetes.

PMID- 19166863
TI  - Age differences in perseveration: cognitive and neuroanatomical mediators of
      performance on the Wisconsin Card Sorting Test.
AB  - Aging effects on the Wisconsin Card Sorting Test (WCST) are fairly well
      established but the mechanisms of the decline are not clearly understood. In this
      study, we examined the cognitive and neural mechanisms mediating age-related
      increases in perseveration on the WCST. MRI-based volumetry and measures of
      selected executive functions in conjunction with the WCST were obtained in a
      sample of 117 healthy young and older adults. Path analysis indicated that age
      related increase in perseveration is completely accounted for by declines in
      processing speed and temporal processing, deficits in working memory mediated by
      decreased prefrontal cortical volume, and the indirect influence of prefrontally
      mediated declines in inhibition via working memory. We conclude that age-related
      increase in perseveration is indeed differentially dependent on the integrity of
      prefrontal cortex and on declines in selected cognitive processes dependent on
      this region.

PMID- 19166864
TI  - Switching between abstract rules reflects disease severity but not dopaminergic
      status in Parkinson's disease.
AB  - This study sought to disambiguate the impact of Parkinson's disease (PD) on
      cognitive control as indexed by task set switching, by addressing discrepancies
      in the literature pertaining to disease severity and paradigm heterogeneity. A
      task set is governed by a rule that determines how relevant stimuli (stimulus
      set) map onto specific responses (response set). Task set switching may entail
      reconfiguration in either or both of these components. Although previous studies
      have shown that PD patients are impaired at switching between stimuli, in the
      present study not all patients were impaired at switching entire task sets, that
      is, both stimulus and response sets: compared with controls, patients with
      unilateral signs (Hoehn & Yahr Stage I) demonstrated intact switching, even
      following withdrawal from dopaminergic medication, while bilaterally affected
      Stage II patients were impaired. The parametric measure of Unified Parkinson's
      Disease Rating Scale (UPDRS) score predicted increasing switch costs within the
      patient group. These findings suggest that switching entire task sets may be a
      function of extrastriatal, possibly non-dopaminergic pathology which increases as
      the disease progresses.

PMID- 19166866
TI  - Relationships between global motion and global form processing, practice,
      cognitive and visual processing in adults with dyslexia or visual discomfort.
AB  - The aim of the first of two experiments was to investigate the effect of practice
      on sensitivity to global motion and global form in a group of adults with
      dyslexia, a group of normal readers with visual discomfort, a group with dyslexia
      and visual discomfort, and a control group. In comparison to the control group,
      and regardless of the effect of practice, the group with dyslexia was
      significantly less sensitive to global motion. No differences in global motion
      sensitivity were found when individuals with dyslexia, with or without visual
      discomfort, were compared. The normal reading group with visual discomfort was
      less sensitive to global motion than the control group at baseline, but not when
      a second estimate of motion sensitivity was obtained. About 30% of the group with
      dyslexia had a global motion deficit on each threshold estimate. In contrast,
      there were no significant effects of practice or group on sensitivity to global
      form. In Experiment 2, performance on a number of cognitive and visual processing
      tasks was measured in four groups: two with dyslexia; one with and one without a
      global motion deficit, a normal reading group with visual discomfort, and a
      control group. The group with visual discomfort had reduced visual processing
      speed only. Regardless of whether a global motion processing deficit was present
      or absent in individuals with dyslexia, reduced accuracy was found on the
      language and visual processing measures, and on a rapid temporal sequencing task.
      Individuals with dyslexia and a global motion deficit had poorer accuracy than
      individuals with dyslexia and no motion deficit on the phonological processing
      and verbal short term memory tasks. We concluded that some adults with dyslexia
      have a persistent deficit when processing global motion but not global form. This
      is consistent with reports of a magnocellular pathway deficit in this group.
      Individuals with visual discomfort do not have a magnocellular processing
      deficit, but have perceptual difficulties when performing complex visual
      processing tasks.

PMID- 19166865
TI  - Aging white matter and cognition: differential effects of regional variations in
      diffusion properties on memory, executive functions, and speed.
AB  - Disruption of cerebral white matter has been proposed as an explanation for age
      related cognitive declines. However, the role of specific regions in specific
      cognitive declines remains unclear. We used diffusion tensor imaging to examine
      the associations between regional microstructural integrity of the white matter
      and performance on age-sensitive cognitive tasks in a sample of healthy adults
      (N=52, age 19-81 years). White matter integrity was assessed by fractional
      anisotropy (FA) and apparent diffusion coefficient (ADC) in multiple regions of
      interest (genu and splenium of corpus callosum, internal capsule limbs,
      prefrontal, temporal, superior/posterior parietal, occipital white matter) and
      related to processing speed, working memory, inhibition, task switching, and
      episodic memory. We found that age and regional white matter integrity
      differentially influenced cognitive performance. Age-related degradation in
      anterior brain areas was associated with decreased processing speed and poorer
      working memory, whereas reduced inhibition and greater task switching costs were
      linked to decline in posterior areas. Poorer episodic memory was associated with
      age-related differences in central white matter regions. The observed multiple
      dissociations among specific age-sensitive cognitive skills and their putative
      neuroanatomical substrates support the view that age-related cognitive declines
      are unlikely to stem from a single cause.

PMID- 19166867
TI  - Cortical bases of elementary deductive reasoning: inference, memory, and
      metadeduction.
AB  - Elementary deduction is the ability of unreflectively drawing conclusions from
      explicit or implicit premises, on the basis of their logical forms. This ability
      is involved in many aspects of human cognition and interactions. To date, limited
      evidence exists on its cortical bases. We propose a model of elementary deduction
      in which logical inferences, memory, and meta-logical control are separable
      subcomponents. We explore deficits in patients with left, medial and right
      frontal lesions, by both studying patients' deductive abilities and providing
      measures of their meta-logical sensitivity for proof difficulty. We show that
      lesions to left lateral and medial frontal cortex impair abilities at solving
      elementary deductive problems, but not so lesions to right frontal cortex.
      Furthermore, we show that memory deficits differentially affect patients
      according to the locus of the lesion. Left lateral patients with working memory
      deficits had defective deductive abilities, but not so left lateral patients with
      spared working memory. In contrast, in medial patients both deductive and meta
      deductive abilities were affected regardless of the presence of memory deficits.
      Overall, the results are compatible with a componential view of elementary
      deduction, and call for the elaboration of more fine-grained models of deductive
      abilities.

PMID- 19166868
TI  - Endocrine and ingestive behavioral responses to fluid deprivation in sheep
      chronically exposed to ethanol.
AB  - Endocrine responses to fluid deprivation/restoration and preference for ethanol
      solution vs. water were assessed in sheep maintained for 5 months on a 10%
      ethanol solution as their sole source of fluid. Blood pressure, body weight,
      plasma composition and hormone levels of the alcohol maintained sheep were all
      within a normal range, except for high plasma concentrations of ANG II and ALDO.
      During fluid deprivation, AVP concentration increased and fluid-deprived sheep
      displayed a natriuresis and then a rehydration anti-natriuresis. Sheep did not
      drink the 10% ethanol solution avidly upon fluid restoration, preferring to drink
      steadily over the following 24 h; there was an associated increase in blood
      alcohol concentration (BAC). PRC, ANG II and ALDO all increased throughout the
      fluid restoration period, whereas plasma AVP and ANP gradually fell. In a
      separate experiment when water was also supplied to the sheep, they preferred
      water to 10% ethanol; however, alcohol intake was not eliminated. Overall, this
      degree of chronic consumption of 10% ethanol solution did not appear to adversely
      affect physiological mechanisms concerned with body fluid homeostasis after fluid
      deprivation conditions.

PMID- 19166869
TI  - EGF-receptor phosphorylation and downstream signaling are activated by
      benzo[a]pyrene 3,6-quinone and benzo[a]pyrene 1,6-quinone in human mammary
      epithelial cells.
AB  - Benzo[a]pyrene (BaP) is activated by xenobiotic-metabolizing enzymes to highly
      mutagenic and carcinogenic metabolites. Previous studies in this laboratory have
      shown that benzo[a]pyrene quinones (BPQs), 1,6-BPQ and 3,6-BPQ, are able to
      induce epidermal growth factor receptor (EGFR) cell signaling through the
      production of reactive oxygen species. Recently, we have reported that BPQs have
      the potential to induce the expression of genes involved in numerous pathways
      associated with cell proliferation and survival in human mammary epithelial
      cells. In the present study we demonstrated that BPQs not only induced EGFR
      tyrosine autophosphorylation, but also induced EGFR-dependent tyrosine
      phosphorylation of phospholipase C-gamma1 and several signal transducers and
      activators of transcription (STATs). The effects of BPQs were evaluated in a
      model of EGF withdrawal in MCF10-A cells. We found that BPQs (1 muM), induced
      EGFR tyrosine phosphorylation at positions Y845, Y992, Y1068, and Y1086. PLC
      gamma1 phosphorylation correlated with the phosphorylation of tyrosine-Y992, a
      proposed docking site for PLC-gamma1 on the EGFR. Additionally, we found that
      BPQs induced the activation of STAT-1, STAT-3, STAT-5a and STAT-5b. STAT5 was
      shown to translocate to the nucleus following 3,6-BPQ and 1,6-BPQ exposures.
      Although the patterns of phosphorylation at EGFR, PLC-gamma1 and STATs were quite
      similar to those induced by EGF, an important difference between BPQ-mediated
      signaling of the EGFR was observed. Signaling produced by EGF ligand produced a
      rapid disappearance of EGFR from the cell surface, whereas BPQ signaling
      maintained EGFR receptors on the cell membrane. Thus, the results of these
      studies show that 1,6-BPQ and 3,6-BPQ can produce early events as evidenced by
      EGFR expression, and a prolonged transactivation of EGFR leading to downstream
      cell signaling pathways.

PMID- 19166870
TI  - On-line contextual influences during reading normal text: The role of nouns,
      verbs and adjectives.
AB  - In a series of multiple-regression analyses conducted on the French part of the
      Dundee corpus, the time spent inspecting a target word in a given sentence was
      found to depend on its degree of semantic relatedness (as assessed in the LSA
      framework) to two content words belonging to a prior part of the sentence, and
      located at varying distances to the left of the target. However, only verb primes
      were found to elicit a significant influence when located in the more remote
      position. In addition, the influence elicited by remote primes was modulated as a
      function of their position in the constituent structure, relative to the position
      of the target. This pattern of results suggests that relatively abstract semantic
      relations, probably involved in processing operations developed at the sentence
      level, can directly influence eye-movement control mechanisms.

PMID- 19166871
TI  - Differential effects of ethanol in the nucleus accumbens shell of alcohol
      preferring (P), alcohol-non-preferring (NP) and Wistar rats: a proteomics study.
AB  - The objective of this study was to determine the effects of ethanol injections on
      protein expression in the nucleus accumbens shell (ACB-sh) of alcohol-preferring
      (P), alcohol-non-preferring (NP) and Wistar (W) rats. Rats were injected for 5
      consecutive days with either saline or 1 g/kg ethanol; 24 h after the last
      injection, rats were killed and brains obtained. Micro-punch samples of the ACB
      sh were homogenized; extracted proteins were subjected to trypsin digestion and
      analyzed with a liquid chromatography-mass spectrometer procedure. Ethanol
      changed expression levels (1.15-fold or higher) of 128 proteins in NP rats, 22
      proteins in P, and 28 proteins in W rats. Few of the changes observed with
      ethanol treatment for NP rats were observed for P and W rats. Many of the changes
      occurred in calcium-calmodulin signaling systems, G-protein signaling systems,
      synaptic structure and histones. Approximately half the changes observed in the
      ACB-sh of P rats were also observed for W rats. Overall, the results indicate a
      unique response to ethanol of the ACB-sh of NP rats compared to P and W rats;
      this unique response may reflect changes in neuronal function in the ACB-sh that
      could contribute to the low alcohol drinking behavior of the NP line.

PMID- 19166872
TI  - Fast food intake among adolescents: secular and longitudinal trends from 1999 to
      2004.
AB  - OBJECTIVES: To examine secular and longitudinal changes (1999-2004) in fast food
      intake among adolescents. METHODS: Adolescents from Minnesota participating in
      Project EAT (n=2516) were surveyed in 1999 and 2004. Mixed-model regressions were
      used to assess secular and longitudinal changes in percentage reporting frequent
      fast food intake (> or =3 times/week) and weekly fast food intake. RESULTS:
      Between 1999 and 2004, a secular increase in the percent of adolescents of middle
      (high school-aged) adolescents reporting frequent fast food consumption was
      observed (females: 18.9% to 27.3%, p<.01, males: 23.6% to 30.2%, p=.06).
      Longitudinal increases in frequent fast food consumption were seen from early to
      middle adolescence (females: 15.8% to 27.3%, p<.01, males: 16.8% to 30.2%,
      p<.01), and among males, from middle to late adolescence (23.6% to 32.0%, p<.01).
      CONCLUSIONS: The secular increase in fast food consumption among middle
      adolescents suggests that socio-environmental changes between 1999 and 2004 may
      have contributed to adolescents' fast food intake, while the longitudinal trends
      indicate the importance of developmental influences on fast food intake. The
      transition from early to middle adolescence, and for males, from middle into late
      adolescence, are key periods during which efforts to reduce fast food consumption
      are needed.

PMID- 19166873
TI  - Assessment of exposure to secondhand smoke by questionnaire and salivary cotinine
      in the general population of Barcelona, Spain (2004-2005).
AB  - OBJECTIVES: To estimate the prevalence of self-reported exposure to secondhand
      smoke (SHS) in different settings and to describe salivary cotinine concentration
      and its determinants among non-smokers. METHODS: Cross-sectional study of a
      representative sample (N=775) of adult non-smokers in Barcelona, Spain (years
      2004-2005). We assessed exposure to SHS using a questionnaire and measurement of
      salivary cotinine concentration. We calculated prevalence rates of self-reported
      exposure and medians and geometric means of salivary cotinine concentration. We
      adjusted for potential confounding factors with multinomial logistic regression
      models. RESULTS: The prevalence rate of self-reported exposure to SHS among non
      smokers in any setting was 75.7% (95% CI: 72.7%-78.8%). The prevalence of
      exposure to SHS tended to decrease with age. The geometric mean of cotinine
      concentrations among non-smokers was 1.49 ng/ml (95% CI: 1.39-1.60 ng/ml) among
      all subjects, and 1.80 ng/ml (95% CI: 1.37-2.35 ng/ml) in subjects who reported
      exposure to SHS in all settings. In bivariate and multivariate analyses, the
      cotinine concentration increased with the number of smokers and the number of
      cigarettes smoked per day in the presence of non-smokers in the household.
      CONCLUSIONS: In this population, self-reported exposure to SHS is very high.
      Salivary cotinine concentrations in non-smokers are associated with exposure at
      home.

PMID- 19166874
TI  - An fMLP receptor is involved in activation of phagocytosis by hemocytes from
      specific insect species.
AB  - In mammalian phagocytes, the bacterial formylated peptide fMLP functions both as
      a potent enhancer of phagocytosis and chemoattractant. fMLP has been reported to
      be chemotactic for hemocytes of two marine invertebrates, and of the insect
      Manduca sexta (Lepidoptera). Whether fMLP is also able to activate phagocytosis
      has not been explored in hemocytes of any invertebrate. To determine the effect
      of fMLP on insect hemocyte phagocytosis, in vitro phagocytosis assays were
      performed with hemocytes from the insects: Gromphadorhina portentosa (Blattodea),
      Acheta domesticus (Orthoptera), Zophobas morio (Coleoptera), and Galleria
      mellonella (Lepidoptera). Phagocytosis of latex, zymosan (yeast), Gram-positive
      and Gram-negative bacteria was measured by flow cytometry, in the presence of
      increasing fMLP concentrations. G. portentosa hemocytes showed no enhancement of
      phagocytosis by fMLP. A. domesticus hemocytes had increased phagocytosis of latex
      and Gram-negative bacteria in the presence of fMLP. Z. morio hemocytes increased
      phagocytosis of latex, yeast, and Gram-negative bacteria after fMLP stimulation.
      Galleria mellonella hemocytes increased phagocytosis of latex after fMLP
      stimulation. Treating hemocytes with Pertussis toxin, a known inhibitor of the
      signaling pathway initiated by the mammalian fMLP receptor, returned phagocytosis
      to basal levels. Also, hemocytes from all insect species tested presented a
      similar chemotactic response to fMLP. These data suggest that, whereas the
      ability of hemocytes to chemotactically-respond to fMLP is conserved in insects
      ranging from Blattodea to Lepidoptera, the ability to respond to fMLP by
      activating phagocytosis is restricted to specific insect species.

PMID- 19166875
TI  - Identification of a porcine DC-SIGN-related C-type lectin, porcine CLEC4G
      (LSECtin), and its order of intron removal during splicing: comparative genomic
      analyses of the cluster of genes CD23/CLEC4G/DC-SIGN among mammalian species.
AB  - Human CLEC4G (previously named LSECtin), DC-SIGN, and L-SIGN are three important
      C-type lectins capable of mediating viral and bacterial pathogen recognitions.
      These three genes, together with CD23, form a lectin gene cluster at chromosome
      19p13.3. In this study, we have experimentally identified the cDNA and the gene
      encoding porcine CLEC4G (pCLEC4G). Full-length pCLEC4G cDNA encodes a type II
      transmembrane protein of 290 amino acids. pCLEC4G gene has the same gene
      structure as the human and the predicted bovine, canis, mouse and rat CLEC4G
      genes with nine exons. A multi-species-conserved site at the extreme 3'
      untranslated region of CLEC4G mRNAs was predicted to be targeted by microRNA miR
      350 in domesticated animals and by miR-145 in primates, respectively. We detected
      pCLEC4G mRNA expression in liver, lymph node and spleen tissues. We also
      identified a series of sequential intermediate products of pCLEC4G pre-mRNA
      during splicing from pig liver. The previously unidentified porcine CD23 cDNA
      containing the complete coding region was subsequently cloned and found to
      express in spleen, thymus and lymph node. Furthermore, we compared the
      chromosomal regions syntenic to the human cluster of genes CD23/CLEC4G/DC-SIGN/L
      SIGN in representative mammalian species including primates, domesticated animal,
      rodents and opossum. The L-SIGN homologues do not exist in non-primates mammals.
      The evolutionary processes of the gene cluster, from marsupials to primates, were
      proposed based upon their genomic structures and phylogenetic relationships.

PMID- 19166878
TI  - Prior sexual experience increases hippocampal cell proliferation and decreases
      risk assessment behavior in response to acute predator odor stress in the male
      rat.
AB  - Acute exposure to the predator odor trimethylthiazoline (TMT) induces defensive
      behavior in the male rat, and this response is associated with a decrease in cell
      proliferation within the dentate gyrus of the hippocampus. Sexual experience
      appears to be protective, as it exerts anxiolytic-like effects and sustains
      gonadal function in the face of stress. To examine the influence of sexual
      experience on subsequent stress-induced defensive behavior and cell proliferation
      in the hippocampus we exposed adult male rats to TMT odor with or without prior
      exposure to sexually receptive female rats. A subset of rats was injected with
      the DNA-synthesis marker bromodeoxyuridine (BrdU; 200 mg/kg) during TMT exposure
      and perfused 24 h later to provide an index of cell proliferation within the
      dentate gyrus. In response to TMT, sexual experience reduced the duration of
      stretched attend postures, but had no significant effect on defensive burying.
      Furthermore, TMT induced a significant increase in cell proliferation in the
      dentate gyrus, but only in males with sexual experience. The results demonstrate
      an influence of socio-sexual experience on the magnitude of the behavioral and
      neural responses to predator odor stress.

PMID- 19166877
TI  - Role of interleukin-1beta during pain and inflammation.
AB  - The cytokine cascade in pain and inflammatory processes is a tremendously complex
      system, involving glial, immune, and neuronal cell interactions. IL-1beta is a
      pro-inflammatory cytokine that has been implicated in pain, inflammation and
      autoimmune conditions. This review will focus on studies that shed light on the
      critical role of IL-1beta in various pain states, including the role of the
      intracellular complex, the inflammasome, which regulates IL-1beta production.
      Evidence will be presented demonstrating the importance of IL-1beta in both the
      induction of pain and in the maintenance of pain in chronic states, such as after
      nerve injury. Additionally, the involvement of IL-1beta as a key mediator in the
      interaction between glia and neurons in pain states will be discussed. Taken
      together, the evidence presented in the current review showing the importance of
      IL-1beta in animal and human pain states, suggests that blockade of IL-1beta be
      considered as a therapeutic opportunity.

PMID- 19166876
TI  - New advances in musculoskeletal pain.
AB  - Non-malignant musculoskeletal pain is the most common clinical symptom that
      causes patients to seek medical attention and is a major cause of disability in
      the world. Musculoskeletal pain can arise from a variety of common conditions
      including osteoarthritis, rheumatoid arthritis, osteoporosis, surgery, low back
      pain and bone fracture. A major problem in designing new therapies to treat
      musculoskeletal pain is that the underlying mechanisms driving musculoskeletal
      pain are not well understood. This lack of knowledge is largely due to the
      scarcity of animal models that closely mirror the human condition which would
      allow the development of a mechanistic understanding and novel therapies to treat
      this pain. To begin to develop a mechanism-based understanding of the factors
      involved in generating musculoskeletal pain, in this review we present recent
      advances in preclinical models of osteoarthritis, post-surgical pain and bone
      fracture pain. The models discussed appear to offer an attractive platform for
      understanding the factors that drive this pain and the preclinical screening of
      novel therapies to treat musculoskeletal pain. Developing both an understanding
      of the mechanisms that drive persistent musculoskeletal pain and novel mechanism
      based therapies to treat these unique pain states would address a major unmet
      clinical need and have significant clinical, economic and societal benefits.

PMID- 19166879
TI  - The importance of nitric oxide in social dysfunction.
AB  - Schizophrenia is a chronic disorder generally considered to encompass positive
      symptoms, negative symptoms and cognitive deficits. Increasing attention has been
      paid to the social cognitive deficits of the disorder as these dysfunctions are
      particularly handicapping, predictive of functional outcome and show poor
      treatment response. Phencyclidine (PCP) is a psychotomimetic drug used to model
      the different aspects of schizophrenia in experimental animal models. PCP-induced
      cognitive deficits and hyperlocomotion may be blocked by pretreatment with nitric
      oxide (NO) synthase inhibitors in rodents. The present study was carried out to
      evaluate the acute effects of PCP and NO synthase inhibition on social
      interaction in male Sprague-Dawley rats. The NO synthase inhibitor, L-NAME
      (10mg/kg) and PCP (2mg/kg) was injected subcutaneously to rats, which were then
      tested in pairs for social interactive behaviour. Twenty-four hours after the
      initial test a drug-free social interaction test was carried out to assess the
      rats' memory of the previous social interaction. The results showed that PCP
      reduced the time of social interaction on Day 1 compared to controls, and that
      pretreatment with the NO synthase inhibitor, L-NAME, attenuated this reduction
      towards control levels. Neither locomotor activity, nor frequency of social
      interactions were affected by the PCP treatment, suggesting that the PCP-induced
      effects observed were not due to drug-induced stereotypies. In combination with
      increasing clinical evidence for the involvement of NO in the pathophysiology of
      schizophrenia, the present results indicate that NO synthase inhibition may be a
      potentially new treatment strategy for alleviating social dysfunction in
      schizophrenia.

PMID- 19166880
TI  - A role for nitrergic system in the antidepressant-like effects of chronic lithium
      treatment in the mouse forced swimming test.
AB  - In the present study we evaluated the involvement of nitric oxide (NO) system in
      the antidepressant-like effects of chronic lithium administration in the mouse
      forced swimming test (FST). Administration of lithium chloride (300 mg/L in
      drinking water for 21 days) had no effect on the immobility of mice in the FST,
      whereas 600 mg/L lithium caused a significant (P<0.001) decrease in the
      immobility time compared with control animals. Administration of the NO synthase
      inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 10mg/kg, daily for a week,
      i.p.) had no significant effect on the immobility time of either control or
      lithium (300 mg/L)-treated mice, whereas acute administration of non-effective
      dose of L-NAME (30 mg/kg, i.p.) caused a robust decrease (P<0.01) in the
      immobility time of lithium (300 mg/L)-treated animals in the FST. Moreover,
      chronic administration of low dose of the NO precursor L-arginine (200 mg/kg,
      daily for a week, i.p.) prevented (P<0.001) the antidepressant-like effects of
      lithium treatment (600 mg/L) in the FST. Acute treatment with L-arginine (200
      mg/kg, i.p.) increased (P<0.05) the immobility time of lithium (600 mg/L)-treated
      mice in the FST. Chronic lithium treatment (600 mg/L but not 300 mg/L) caused a
      significant (P<0.05) decrease in the serum NO(X) levels in mice compared with
      controls. Our data suggested that the NO system could be involved in the
      antidepressant-like effect of chronic lithium treatment in the FST.

PMID- 19166881
TI  - Human initiator caspases trigger apoptotic and autophagic phenotypes in
      Saccharomyces cerevisiae.
AB  - Caspases are a family of proteases that participate in the progression and
      execution of the apoptotic program. However, regulation of the caspase activation
      and their substrates has not yet been fully elucidated. Here we explore the
      effect of the ectopic expression of the human initiator caspases-8 and -10 in
      Saccharomyces cerevisiae. Our results showed that the expression of human CASP10
      and CASP8 triggers certain apoptotic markers such as a massive production of
      reactive oxygen species (ROS), chromatin condensation and phosphatidylserine
      externalization, finally leading to cell death. In response to hydroxyurea (HU),
      yeast cells expressing caspase-10 did not reduce the replication of DNA and
      escaped to the intra-S checkpoint of the cell cycle. In addition, caspase-10
      expression induced yeast vacuolization and a vacuole-associated phenotype
      resembling autophagy. Other intracellular alterations such as disorganization of
      the actin cytoskeleton, cell wall damage, and aberrations within the endoplasmic
      reticulum lumen were also associated with caspase-10 expression. Furthermore,
      caspase-induced cell death was completely dependent on the proteolytic activation
      of the enzyme but, in contrast, was not dependent on either of the endogenous
      yeast apoptotic proteins Aif1 and Mca1 or the mitochondria.

PMID- 19166882
TI  - Discovery of marine Bacillus species by 16S rRNA and rpoB comparisons and their
      usefulness for species identification.
AB  - Systematic studies of the Bacillus group have been biased towards terrestrial and
      pathogenic isolates, and relatively few studies have examined Bacillus species
      from marine environments. Here we took twenty Bacillus strains from diverse
      marine environments and sequenced their 16S rRNA. Using molecular comparisons, we
      separated the strains into thirteen Bacillus genotypes and identified 9 species:
      B. aquaemaris. B. badius, B. cereus group, B. firmus, B. halmapalus, B.
      hwajinpoensis, B. litoralis, B. sporothermodurans, B. vietnamensis, and three
      indistinguishable Bacilli. In addition, we sequenced the DNA-directed RNA
      polymerase beta subunit (rpoB) gene and assessed its discriminative power in
      identifying Bacilli. Phylogenetic trees of Bacillus rpoB genes separated each
      Bacillus according to their taxonomic positions and were supported statistically.
      The resolution of Bacillus on the rpoB phylogenetic tree was approximately 4.5
      times greater than on the 16S rRNA phylogenetic tree. These results demonstrate
      that the polymorphism of the Bacillus rpoB gene can be used to identify Bacillus
      species, providing an improved identification scheme for Bacillus species.

PMID- 19166883
TI  - Development of a culture independent method to characterize the chemotactic
      response of Flavobacterium columnare to fish mucus.
AB  - Flavobacterium columnare, the causative agent of columnaris disease, is a
      significant pathogen of many freshwater fish species worldwide and is considered
      one of the most important pathogens impacting the channel catfish (Ictalurus
      punctatus Rafinesque) industry in the United States. Recent research has
      demonstrated that F. columnare exhibits a chemotactic response to mucus from the
      skin of catfish and this response may be important for pathogenesis. In this
      study, a culture independent method was developed to quantify the chemotactic
      response of F. columnare to skin mucus. The method employs the use of blind-well
      chemotaxis chambers which overcomes difficulties using the traditional capillary
      tube assay and uses a cell proliferation assay to quantify viable cells which
      reduces the time and labor associated with culturing the bacterium. Application
      of the method to two sets of catfish skin mucus samples demonstrated that there
      is variation in the chemotactic response of F. columnare to individual catfish
      mucus samples, and similar results were obtained to previously published research
      using the traditional capillary tube method. The use of this method will enhance
      the ability to further characterize the chemotactic response of F. columnare to
      catfish skin mucus in order to increase the understanding of this important host
      pathogen interaction.

PMID- 19166884
TI  - Chaos in schizophrenia associations, reality or metaphor?
AB  - There is evidence that schizophrenic associations display "chaotic", random-like
      behavior and decreased predictability. The evidence suggests a hypothesis that
      the "chaotic" mental disorganization could be explained within the concept of
      nonlinear dynamics and complexity in the brain that may cause chaotic neural
      organization. Testing of the hypothesis in the present study was performed using
      nonlinear analysis of bilateral electrodermal activity (EDA) during resting state
      and an association test in 56 schizophrenic patients and 44 healthy participants.
      EDA is a suitable measure of brain and autonomic activity reflecting
      neurobiological changes in schizophrenia that may indicate changes in nonlinear
      neural dynamics related to associative process. The results show that
      quantitative indices of chaotic dynamics (the largest Lyapunov exponents)
      calculated from EDA signals recorded during rest and the association test are
      significantly higher in schizophrenia patients than in the control group and
      increase during the test in comparison to the resting state. The difference was
      confirmed by statistical methods and using surrogate data testing that rejected
      an explanation within the linear statistical framework. The results provide
      supportive evidence that pseudo-randomness of schizophrenic associations and less
      predictability could be linked to increased complexity of nonlinear neural
      dynamics, although certain limitations in data interpretation must be taken into
      account.

PMID- 19166885
TI  - Coating of adenovirus type 5 with polymers containing quaternary amines prevents
      binding to blood components.
AB  - Adenovirus type 5 (Ad5) gene therapy vectors require protection against
      antibodies, complement proteins and blood cells if they are to be delivered
      intravenously to treat metastatic disease. Such protection can be achieved by
      chemically modifying Ad5 with polymers based on hydrophilic HPMA. Here, such
      polymers were designed to include side chains bearing reactive carbonyl
      thiazolidine-2-thione groups (TTs) to covalently modify available amino groups of
      the lysine residues in the Ad5 capsid. Furthermore, the inclusion of side chains
      bearing positively charged quaternary ammonium groups (QAs) was designed to
      improve electrostatic interaction of the polymers with negatively charged Ad5
      hexon protein. Finally, to enable triggered uncoating and reactivation of the
      Ad5, either the TTs or both the TTs and the QAs were linked to polymer backbone
      via reductively degradable disulfide bonds. SDS-PAGE demonstrated that these
      polymers covalently modified Ad5 capsid proteins in a reduction reversible
      manner. In infection studies, polymers containing QAs prevented binding of
      coagulation factor X to Ad5. Furthermore, the antibody and complement mediated
      binding of Ad5 to erythrocytes was reduced by such polymers (>95% without
      polymer, 25% following coating). These data indicate that coating Ad5
      therapeutics with such polymers will improve blood circulation half-life and
      deposition at disease sites.

PMID- 19166886
TI  - Genomics: applications in mechanism elucidation.
AB  - The inability to predict the pharmacology and toxicology of drug candidates in
      preclinical studies has led to the decline in the number of new drugs which make
      it to market and the rise in cost associated with drug development. Identifying
      molecular interactions associated with therapeutic and toxic drug effects early
      in development is a top priority. Traditional mechanism elucidation strategies
      are narrow, often focusing on the identification of solely the molecular target.
      Methods which can offer additional insight into wide-ranging molecular
      interactions required for drug effect and the biochemical consequences of these
      interactions are in demand. Genomic strategies have made impressive advances in
      defining a more global view of drug action and are expected to increasingly be
      used as a complimentary tool in drug discovery and development.

PMID- 19166887
TI  - CpG oligonucleotide as an adjuvant for the treatment of prostate cancer.
AB  - The use of an adenovirus transduced to express a prostate cancer antigen (PSA) as
      a vaccine for the treatment of prostate cancer has been shown to be active in the
      destruction of antigen-expressing prostate tumor cells in a pre-clinical model,
      using Balb/C or PSA transgenic mice. The destruction of PSA-secreting mouse
      prostate tumors was observed in Ad/PSA immunized mice in a prophylaxis study with
      70% of the mice surviving long term tumor free. This successful immunotherapy was
      not observed in therapeutic studies in which tumors were established before
      vaccination and the development of anti-PSA immune response was not as easily
      generated in PSA transgenic mice. Immunization of conventional and transgenic
      animals was enhanced by incorporating a collagen matrix into the immunizing
      injection. Therefore the need to strengthen anti-PSA and anti-prostate cancer
      immunity was an obvious next step in developing a successful prostate cancer
      immunotherapy. Because the use of immunostimulatory CpG motifs was shown to
      enhance immune responses to a wide variety of antigens, our studies incorporated
      CpG into the Ad/PSA vaccine experimental plans. The results of the subsequent
      studies demonstrated a dichotomy where Ad/PSA plus CpG enhanced the in vivo
      destruction of PSA-secreting tumors and the survival of experimental animals, but
      revealed that the number and in vitro activities of antigen specific CD8+ T cells
      was decreased as compared to the values observed when the vaccine alone was used
      for immunization. The dichotomous observations were confirmed using another
      antigen system, OVA also incorporated into a replication defective adenovirus.
      Despite the reduction in antigen-specific CD8+ cells after vaccine plus CpG
      immunization the enhanced destruction of sc and systemic tumors was shown to be
      mediated entirely by CD8+ T cells. Finally, the reduction of the CD8+ T cells was
      the result of an observed decrease in the proliferation of the antigen specific
      cell population.

PMID- 19166888
TI  - CpG oligonucleotides as immunotherapeutic adjuvants: innovative applications and
      delivery strategies.

PMID- 19166891
TI  - Melatonin enhances the immune response to vaccination against A1 and C strains of
      Dichelobacter nodosus.
AB  - Melatonin has been shown to exert immunomodulatory properties with broad
      application in veterinary medicine. Here we have investigated the effect of
      exogenous melatonin in the improvement of the immune response to administration
      of an immune-preparation of two stumps of A1 and C strains of Dichelobacter
      nodosus in sheep. Subcutaneous administration of melatonin enhanced plasma levels
      of melatonin from days 42 to 120. Administration of melatonin to vaccinated
      animals enhanced both the titer of antibodies and serum IgG levels to A1 and C
      strains of D. nodosus compared to vaccinated animals not treated with melatonin.
      Our results suggest that melatonin increased the immune response to vaccination
      and open new perspectives in the design of prophylactic strategies.

PMID- 19166892
TI  - Mice orally vaccinated with Edwardsiella tarda ghosts are significantly protected
      against infection.
AB  - Bacterial ghosts may be generated by the controlled expression of the phiX174
      lysis gene E in Gram-negative bacteria and they are intriguing vaccine candidates
      since ghosts retain functional antigenic cellular determinants often lost during
      traditional inactivation procedures. The Edwardsiella tarda ghost (ETG) vaccine
      was prepared using this technology and tested in vaccination trials. Control
      groups included mice immunized with formalin-killed E. tarda (FKC) or mice
      treated with phosphate-buffered saline (PBS), respectively. The results showed
      that serum IgA and IgG antibody titers were significantly higher in the ETG
      vaccinated group compared to the other groups. In addition, CD8+ T cell counts in
      peripheral blood were elevated in the ETG groups. Most important, ETG-immunized
      mice were significantly protected against E. tarda challenge (86.7% survival)
      compared to 73.3 and 33.3% survival in the FKC-immunized and PBS-treated control,
      respectively, suggesting that an ETG oral vaccine could confer protection against
      infection in a mouse model of disease.

PMID- 19166889
TI  - Micro- and macrorheology of mucus.
AB  - Mucus is a complex biological material that lubricates and protects the human
      lungs, gastrointestinal (GI) tract, vagina, eyes, and other moist mucosal
      surfaces. Mucus serves as a physical barrier against foreign particles, including
      toxins, pathogens, and environmental ultrafine particles, while allowing rapid
      passage of selected gases, ions, nutrients, and many proteins. Its selective
      barrier properties are precisely regulated at the biochemical level across vastly
      different length scales. At the macroscale, mucus behaves as a non-Newtonian gel,
      distinguished from classical solids and liquids by its response to shear rate and
      shear stress, while, at the nanoscale, it behaves as a low viscosity fluid.
      Advances in the rheological characterization of mucus from the macroscopic to
      nanoscopic levels have contributed critical understanding to mucus physiology,
      disease pathology, and the development of drug delivery systems designed for use
      at mucosal surfaces. This article reviews the biochemistry that governs mucus
      rheology, the macro- and microrheology of human and laboratory animal mucus,
      rheological techniques applied to mucus, and the importance of an improved
      understanding of the physical properties of mucus to advancing the field of drug
      and gene delivery.

PMID- 19166893
TI  - Evaluation of human relevance and mode of action for tunica vaginalis
      mesotheliomas resulting from oral exposure to acrylamide.
AB  - The human relevance and mode of action of acrylamide-related tunica vaginalis
      mesotheliomas (TVMs), a tumor of the scrotum, was evaluated based on the
      available data on acrylamide and general biology considerations. TVMs are found
      almost exclusively in F344 rats, suggesting an association with the hormonal
      milieu unique to F344s, and suggesting an association with Leydig cell tumors
      (LCTs), which occur in F344 rats at a very high incidence. These hypotheses are
      biologically plausible, but direct data on acrylamide were lacking for several
      key events; some of the gaps could be addressed based on other biology
      information. The data were not sufficient to identify a single definitive MOA.
      Multiple MOAs may apply, and some contribution from mutagenicity is plausible,
      along with a likely influence from LCTs or from the same hormonal changes that
      result in higher LCT incidence in F344 rats. Other MOAs, such as oxidative
      stress, may also apply. The data reviewed are not sufficient to distinguish
      between a causal relationship between LCTs and TVMs, and the hypothesis that
      these tumor types reflect a response to some shared influence (e.g., hormonal
      milieu of the F344 rat). Some of the plausible MOAs are not relevant to humans,
      while others are. In light of the very low incidence of TVMs in humans and the
      MOA data reviewed, the most appropriate upper bound estimate of the risk of
      acrylamide-related TVMs in humans is below de minimis levels.

PMID- 19166894
TI  - Does hypofrontality expand to global brain area in progression of schizophrenia?:
      a cross-sectional study between first-episode and chronic schizophrenia.
AB  - Although to date there have been no conclusive pathophysiological findings in
      support of the degenerative theory of the etiology of schizophrenia, the results
      of neuroimaging studies have suggested that progressive changes in the brain do
      occur during the clinical course of schizophrenia. However, there has been no
      report on alterations in regional cerebral blood flow (rCBF) under resting
      condition, which was compared between the first-episode and the chronic patients
      of schizophrenia and healthy controls. Therefore, in this study, we applied three
      dimensional stereotactic surface projection analysis of resting SPECT (3D-SSP
      SPECT) in patients with first-episode (n=18) and chronic schizophrenia (n=23) and
      age-/sex-matched healthy controls (n=40). The rCBFs in the middle/inferior/medial
      frontal gyrus and the anterior cingulate gyrus were significantly decreased in
      both patient groups, relative to the respective controls (Z>3.0, P<0.001,
      uncorrected). The chronic group showed significant hypoperfused region in the
      left inferior parietal lobule and middle/inferior temporal gyrus. Furthermore,
      within-cases comparison between the first-episode and chronic schizophrenia,
      revealed that the significant hypoperfused regions in the chronic group, compared
      to the first-episode group, were not only the lateral and medial prefrontal
      cortex, but also the inferior parietal cortex, posterior part of the temporal
      lobe, and the cuneus. The present study suggested that the reduction in rCBF
      occurs in the posterior brain area in addition to the frontal lobe across all
      clinical stages of schizophrenia.

PMID- 19166895
TI  - Supersensitivity psychosis after tapering aripiprazole: a case report.

PMID- 19166896
TI  - Augmentation of antidepressants with perospirone for treatment-resistant major
      depressive disorder.
AB  - We examined the efficacy and tolerability of perospirone, a dopamine D2 and 5
      HT2A receptor antagonist and a partial 5-HT1A receptor agonist, in the
      augmentation of antidepressant treatment of partially responding and
      nonresponding patients with major depressive disorder. Twelve patients with major
      depressive disorder and an incomplete or no response to different kinds of
      antidepressants (selective serotonin reuptake inhibitor, milnacipran, or
      sulpride) monotherapy or polytherapy for 8 weeks or more were treated with
      perospirone augmentation in an eight-week, open-label study. Data were gathered
      from July 2006 to March 2008. The mean duration of antidepressant pharmacotherapy
      at baseline was 28 weeks. At baseline, the mean (+/-SD) of the MADRS scores was
      35.8+/-10.1. The mean (+/-SD) initial dose of perospirone was 7.0+/-2.9 mg/day
      and the final dose was 11.7+/-6.6 mg/day. Significant reductions in MADRS scores
      were observed at weeks 2, 4, 6 and 8. Although two of the twelve subjects who
      completed the protocol achieved remission by the study endpoint, five of the
      twelve patients were responders (i.e., >50% improvement in the MADRS score).
      Sleepiness and tremor were observed in six patients and one patient,
      respectively, resulting in a reduction of perospirone dose due to these side
      effects. The discontinuation rate after 8 weeks of treatment was zero. These
      findings suggest that perospirone may be an effective augmentation strategy for
      improving therapeutic response in patients with treatment-resistant major
      depressive disorder when administered in combination with standard antidepressant
      therapy. Based on this clinical evidence, a double-blind, placebo-controlled
      trial is warranted.

PMID- 19166898
TI  - Safety and antipsychotic efficacy of "forced" intramuscular olanzapine over five
      days: a case report.

PMID- 19166897
TI  - Evaluation of the effects of vitamin A supplementation on adult rat substantia
      nigra and striatum redox and bioenergetic states: mitochondrial impairment,
      increased 3-nitrotyrosine and alpha-synuclein, but decreased D2 receptor
      contents.
AB  - Vitamin A at moderate to high doses is applied in the treatment of some life
      threatening pathological conditions, for instance cancers. Additionally, vitamin
      A at low concentrations is a known antioxidant molecule. However, by increasing
      vitamin A (or its derivatives) concentrations, there is an increase in the levels
      of oxidative stress markers in several experimental models. Furthermore, it was
      reported that vitamin A therapy at high doses might induce cognitive decline
      among the patients, which may become anxious or depressive, for example,
      depending on vitamin A levels intake. We have previously reported increased
      levels of oxidative stress markers in rat substantia nigra and striatum. However,
      the mechanism by which this vitamin altered the redox environment in such rat
      brain regions remains to be elucidated. In the herein presented work, we have
      investigated the effects of vitamin A supplementation at clinical doses (1000
      9000 IU/kg day(-1)) for 28 days on rat substantia nigra and striatum
      mitochondrial electron transfer chain (METC) activity, which may produce
      superoxide anion radical (O(2)(-*)) when impaired. Additionally, the levels of
      non-enzymatic antioxidant defenses were evaluated, as well as 3-nitrotyrosine,
      alpha- and beta-synucleins and TNF-alpha levels through ELISA assay. We observed
      impaired METC in both rat brain regions. Moreover, we found increased O(2)(-*)
      production and nitrotyrosine content in the nigrostriatal axis of vitamin A
      treated rats, suggesting that the use of vitamin A at therapeutic doses may be
      rethought due to this toxic effects found here.

PMID- 19166899
TI  - Therapeutic effects of the selective serotonin noradrenaline reuptake inhibitor
      milnacipran on depressive symptoms in patients with Alzheimer's disease.
AB  - To clarify the profile of depressive symptoms in major depressive episodes in
      patients with Alzheimer's disease (AD-MD), we compared AD-MD with major
      depressive disorder in non-demented elderly patients (MDD) matched for age, using
      the 17-item Hamilton Rating Scale for Depression (HAM-D(17)). In addition, to
      clarify which depressive symptoms of AD patients respond to treatment with the
      selective serotonin and noradrenaline reuptake inhibitor (SNRI) milnacipran, we
      compared the HAM-D(17) average score and the score of each HAM-D item, the mini
      mental state examination (MMSE) score, and GAF score according to the DSM-IV
      evaluation of AD-MD patients at baseline and at the endpoint (12 weeks).
      Depressive mood, loss of interest in hobbies and social activities and anxiety
      (psychic) scored the highest in both AD-MD and MDD groups, while psychomotor
      retardation scored significantly higher in AD-MD, and insomnia and anxiety
      (somatic) significantly did so in MDD. We also found that depressive mood,
      suicidal tendency, loss of interest, psychomotor retardation, anxiety (psychic),
      gastrointestinal symptoms, general somatic symptoms, and hypochondriasis
      remarkably improved in patients of AD-MD treated with milnacipran. Our results
      suggest that in general the profiles of depression in AD-MD and MDD are similar,
      despite some different clinical features between both conditions. Our study also
      suggests that milnacipran is promising to treat a broad range of depressive
      symptoms in AD-MD patients.

PMID- 19166900
TI  - Chronic toxicity and carcinogenicity studies of chromium picolinate monohydrate
      administered in feed to F344/N rats and B6C3F1 mice for 2 years.
AB  - Trivalent chromium (Cr(III)) has been proposed to be an essential element, which
      may increase sensitivity to insulin and thus participate in carbohydrate and
      lipid metabolism. Humans ingest Cr(III) both as a natural dietary constituent and
      in dietary supplements taken for weight loss and antidiabetic effects. Chromium
      picolinate (CP), a widely used supplement, contains Cr(III) chelated with three
      molecules of picolinic acid and was formulated in an attempt to improve the
      absorption of Cr(III). In order to examine the potential for CP to induce chronic
      toxicity and carcinogenicity, the NTP conducted studies of the monohydrate form
      (CPM) in groups of 50 male and female F344/N rats and B6C3F1 mice exposed in feed
      to concentrations of 0, 2000, 10,000 or 50,000 ppm for 2 years; exposure
      concentrations were selected following review of the data from NTP 3-month
      toxicity studies. Exposure to CPM did not induce biologically significant changes
      in survival, body weight, feed consumption, or non-neoplastic lesions in rats or
      mice. In male rats, a statistically significant increase in the incidence of
      preputial gland adenoma at 10,000 ppm was considered an equivocal finding. CPM
      was not carcinogenic to female rats or to male or female mice.

PMID- 19166902
TI  - Effect of 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on oxidative stress in
      cerebral cortex of rats.
AB  - The objective of this study was to verify the effect of the organochalcogen 3
      butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on some parameters of oxidative
      stress in the brain of 10-day-old rats. Cerebral cortex was incubated for 1h in
      the presence or absence of 1, 10 or 30 microM of 3-butyl-1-phenyl-2
      (phenyltelluro)oct-en-1-one and thiobarbituric acid reactive substances (TBARS),
      carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD), glutathione
      peroxidase (GPx), glutathione S-transferase (GST), nitric oxide (NO) production
      and the release of the cytosolic enzyme lactate dehydrogenase (LDH) were
      measured. The organotellurium was not capable to alter TBARS and carbonyl assays.
      In contrast, the compound at 10 and 30 microM provoked a reduced of protein thiol
      groups measured by the sulfhydryl assay. Furthermore, the activity of the
      antioxidant enzyme CAT (10 and 30 microM) and GPx (1, 10 and 30 microM) was
      reduced by the organochalcogen. On the other hand, the activity of SOD and GST
      were enhanced respectively by 1, 10 and 30 microM of the compound. Furthermore,
      NO production was also increased by 30muM of this organochalcogen. Finally, we
      verified that the organotellurium was capable of enhance the LDH release at 30
      microM concentration. Our findings indicate that this organotellurium compound
      induces in vitro oxidative stress in the cerebral cortex of rats being
      potentially toxic for the brain of rats.

PMID- 19166901
TI  - Acrylamide: Consideration of species differences and nonlinear processes in
      estimating risk and safety for human ingestion.
AB  - Acrylamide in cooked foods results in wide-spread, low-level human exposure.
      Potential risks from dietary intake remain unclear due to apparent conflicting
      results from cancer bioassays conducted in rats that reported tumors and
      epidemiology studies that are suggestive but provide little or no evidence of
      increased cancer. Risk estimation often includes two common assumptions: (1)
      tumor response rates in test species can be extrapolated systematically to
      estimate human response rates and (2) tumor rates observed following high-dose
      exposures can be linearly extrapolated to predict response rates following low
      dose exposures. The validity of these assumptions was evaluated for acrylamide
      based upon the examination of relevant toxicokinetic and toxicodynamic
      differences between humans and rats, including sources of nonlinearity that
      modify high to low dose extrapolation of cancer incidence. Important species
      differences and sources of nonlinearity are identified, and recommendations for
      addressing them within the quantitative framework of a PBTK/TD model are
      discussed. These differences are likely to estimate risk levels up to several
      orders of magnitude lower in humans than in rats. Quantitative inclusion of these
      TK/TD factors will more closely estimate actual human cancer risk derived from
      high-dose rodent studies, since detoxification processes for acrylamide and
      glycidamide appear adequately protective against toxicity from human dietary
      doses.

PMID- 19166903
TI  - The VEP1 gene (At4g24220) encodes a short-chain dehydrogenase/reductase with 3
      oxo-Delta4,5-steroid 5beta-reductase activity in Arabidopsis thaliana L.
AB  - The Arabidopsis thaliana VEP1 gene product shows about 70% sequence identity to
      Digitalis lanata progesterone 5beta-reductase, an enzyme considered to catalyze a
      key step in the biosynthesis of cardiac glycosides. A. thaliana does not
      accumulate cardenolides but protein extracts prepared from its leaves were
      capable of reducing progesterone to 5beta-pregnane-3,20-dione. A full-length cDNA
      clone encoding a Delta(4,5)-steroid 5beta-reductase (At5beta-StR, EC
      1.1.1.145/1.3.1.23), a member of the short-chain dehydrogenase/reductase (SDR)
      family, was isolated from A. thaliana leaves. A SphI/SalI At5beta-StR gene
      fragment was cloned into the pQE vector system and transformed into Escherichia
      coli. The gene was functionally expressed and the recombinant His-tagged fusion
      protein was characterized. K(m) values and specific activities for putative 3-oxo
      Delta(4,5)-steroid substrates such as progesterone, cortisol, cortexone and 4
      androstene-3,17-dione, and for the co-substrate NADPH were determined.
      Progesterone was stereo-specifically reduced to 5beta-pregnane-3,20-dione and
      none of the 3-oxo-Delta(5,6)-steroids tested were accepted as a substrate. The
      gene encoding At5beta-StR was strongly transcribed in stems and leaves. A three
      dimensional model of At5beta-StR highlights a close structural similarity to the
      related, previously described D. lanata progesterone 5beta-reductase. This
      homology extends to the active site where single amino acid substitutions might
      be responsible for the increased catalytic efficiency of At5beta-StR when
      compared to the activity of the recombinant form of the D. lanata enzyme.

PMID- 19166905
TI  - The dynamic and static modification of the epigenome by hormones: a role in the
      developmental origin of hormone related cancers.
AB  - There are numerous diseases associated with abnormal hormonal regulation and
      these include cancers of the breast and prostate. There is substantial evidence
      that early hormonal perturbations (in utero or during early development) are
      associated with increased disease susceptibility later in life. These
      perturbations may arise from exposure to environmental agents or endocrine
      disruptors which mimic hormones and disrupt normal hormonal signaling. Epigenetic
      alterations have often been proposed as the underlying mechanism by which early
      hormonal perturbations may give rise to disease in adulthood. Currently, there is
      minimal evidence to support a direct link between early hormonal perturbations
      and epigenetic modifications; or between epigenetic alterations and subsequent
      onset of cancer. Given that epigenetic modifications may play an important role
      in hormone-dependent cancers, it is essential to better understand the
      relationship between the hormonal environment and epigenetic modifications in
      both normal and disease states. In this review, we highlight several important
      studies which support the hypothesis that: hormonal perturbations early in life
      may result in epigenetic changes that may modify hormone receptor function,
      thereby contributing to an increased risk of developing hormone-related cancers.

PMID- 19166906
TI  - The XLMR gene ACSL4 plays a role in dendritic spine architecture.
AB  - ACSL4 is a gene involved in non-syndromic X-linked mental retardation. It encodes
      for a ubiquitous protein that adds coenzyme A to long-chain fatty acids, with a
      high substrate preference for arachidonic acid. It presents also a brain-specific
      isoform deriving from an alternative splicing and containing 41 additional N
      terminal amino acids. To start to unravelling the link between ACSL4 and mental
      retardation, we have performed molecular and cell biological studies. By retro
      transcription polymerase chain reaction analyses we identified a new transcript
      with a shorter 5'-UTR region. By immunofluorescence microscopy in embryonic rat
      hippocampal neurons we report that ACSL4 is associated preferentially to
      endoplasmic reticulum tubules. ACSL4 knockdown by siRNAs in hippocampal neurons
      indicated that this protein is largely dispensable for these cells' gross
      architectural features (i.e. axonal and dendritic formation and final length) yet
      it is required for the presence of normal spines. In fact, reduced levels of
      ACSL4 led to a significant reduction in dendritic spine density and an alteration
      in spine/filopodia distribution. The possible mechanisms behind this phenotype
      are discussed.

PMID- 19166907
TI  - Deafferentation-induced caspase-3 activation and DNA fragmentation in chick
      cochlear nucleus neurons.
AB  - Cochlea removal severs peripheral processes of cochlear ganglion cells and
      permanently abolishes afferent input to nucleus magnocellularis (NM) neurons.
      Deafferented chick NM neurons undergo a series of morphologic and metabolic
      changes, which ultimately trigger the death of 20%-40% of neurons. Previous
      studies suggested that this cell specific death involves activation of the
      intrinsic apoptotic pathway, including increased presence of cytochrome c and
      active caspase-9 in the cytoplasm of deafferented NM neurons. Interestingly,
      however, both markers were detected pan-neuronally, in both degenerating and
      surviving NM neurons [Wilkinson BL, Elam JS, Fadool DA, Hyson RL (2003) Afferent
      regulation of cytochrome-c and active caspase-9 in the avian cochlear nucleus.
      Neuroscience 120:1071-1079]. Here, we provide evidence for the increased
      appearance of late apoptotic indicators and describe novel characteristics of
      cell death in deafferented auditory neurons. Young broiler chickens were
      subjected to unilateral cochlea removal, and brainstem sections through NM were
      reacted for active caspase-3 and terminal deoxynucleotidyl transferase-mediated
      dUTP nick-end labeling (TUNEL). Caspase-3 activation is observed in the cytoplasm
      of both dying and surviving deafferented NM neurons 24 h to 7 days following
      cochlea removal, suggesting that caspase-3, usually considered an "executioner"
      of apoptotic death, may also function as a "modulator" of death. In addition, we
      find that TUNEL labeling of degraded DNA is observed in deafferented NM. In
      contrast to upstream apoptotic markers, however, TUNEL labeling is restricted to
      a subpopulation of deafferented neurons. Twelve hours following cochlea removal,
      TUNEL labeling is observed as punctate accumulations within nuclei. Twenty-four
      hours following cochlea removal, TUNEL accumulates diffusely throughout neuronal
      cytoplasm in those neurons likely to die. This cytoplasmic TUNEL labeling may
      implicate mitochondrial nucleic acid degradation in the selective death of some
      deafferented NM neurons. Our study examines the subcellular distributions of two
      prominent apoptotic mediators, active caspase-3 and TUNEL, relative to known
      histochemical markers, in deafferented NM; provides new insight into the
      apoptotic mechanism of cell death; and proposes a role for mitochondrial DNA in
      deafferentation-induced cell death.

PMID- 19166904
TI  - Amyloid precursor protein and alpha synuclein translation, implications for iron
      and inflammation in neurodegenerative diseases.
AB  - Recent studies that alleles in the hemochromatosis gene may accelerate the onset
      of Alzheimer's disease by five years have validated interest in the model in
      which metals (particularly iron) accelerate disease course. Biochemical and
      biophysical measurements demonstrated the presence of elevated levels of
      neurotoxic copper zinc and iron in the brains of AD patients. Intracellular
      levels of APP holoprotein were shown to be modulated by iron by a mechanism that
      is similar to the translation control of the ferritin L- and H mRNAs by iron
      responsive element (IRE) RNA stem loops in their 5' untranslated regions
      (5'UTRs). More recently a putative IRE-like sequence was hypothesized present in
      the Parkinsons's alpha synuclein (ASYN) transcript (see [A.L. Friedlich, R.E.
      Tanzi, J.T. Rogers, The 5'-untranslated region of Parkinson's disease alpha
      synuclein messenger RNA contains a predicted iron responsive element, Mol.
      Psychiatry 12 (2007) 222-223. [6]]). Together with the demonstration of metal
      dependent translation of APP mRNA, the involvement of metals in the plaque of AD
      patients and of increased iron in striatal neurons in the substantia nigra (SN)
      of Parkinson's disease patients have stimulated the development of metal
      attenuating agents and iron chelators as a major new therapeutic strategy for the
      treatment of these neurodegenerative diseases. In the case of AD, metal based
      therapeutics may ultimately prove more cost effective than the use of an amyloid
      vaccine as the preferred anti-amyloid therapeutic strategy to ameliorate the
      cognitive decline of AD patients.

PMID- 19166908
TI  - Error processing in normal aging and in basal ganglia disorders.
AB  - Recently it has been shown that effects of aging and pathologically induced
      changes of basal ganglia structures may have quite similar effects on cognitive
      functions mediated by the medial prefrontal cortex. The question appears, if this
      pattern may be assignable to other cognitive functions that are mediated via the
      basal ganglia and medial prefrontal brain areas. Error processing is a component
      of executive functions that also depends on these areas and especially on the
      anterior cingulate cortex (ACC). Hence we ask, if error processing functions are
      differentially modulated by normal aging and basal ganglia diseases. Error
      processing mechanisms in these groups were investigated using a cognitive event
      related potential (ERP), the error negativity. Enrolling an extended sample of
      young and elderly controls, as well as patients with Parkinson's and Huntington's
      disease, we show that modulations of error processing differ between aging,
      different basal ganglia diseases. Despite that the examined basal ganglia
      disorder groups (Parkinson's and Huntington's disease) differ in their age they
      show similar modulations in error processing, suggesting that aging effects are
      overridden by pathogenic effects. The study shows that it may be valuable to
      compare aging not only to different forms of basal ganglia disorders in order to
      gain knowledge about age- and disease-related mechanisms and the effects of these
      on cognitive functions. Diseases of the basal ganglia may impact error processing
      above and beyond the effects of normal aging. Although many aging, Parkinson's
      disease and Huntington's disease studies on error processing functions have
      already been published, this study ties together several related observations
      across all of these groups in one experiment.

PMID- 19166909
TI  - Influence of parallel fiber-Purkinje cell synapse formation on postnatal
      development of climbing fiber-Purkinje cell synapses in the cerebellum.
AB  - The climbing fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides
      an ideal model for the study of developmental rearrangements of neural circuits.
      At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated
      during postnatal development, and mono innervation is attained by postnatal day
      20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with
      "hypogranular" cerebella indicate that regression of surplus CFs requires normal
      generation of granule cells and their axons, parallel fibers (PFs), and normal
      formation of PF-PC synapses. Our understanding of how PF-PC synapse formation
      affects development of CF-PC synapse has been greatly advanced by analyses of
      mutant mice deficient in glutamate receptor delta2 subunit (GluRdelta2), an
      orphan receptor expressed selectively in PCs. Deletion of GluRdelta2 results in
      impairment of PF-PC synapse formation, which leads to defects in development of
      CF-PC synapses. In this article, we review how impaired PF-PC synapse formation
      affects wiring of CFs to PCs based mostly on our data on GluRdelta2 knockout
      mice. We propose a new scheme that CF-PC synapses are shaped by the three
      consecutive events, namely functional differentiation of multiple CFs into one
      strong and a few weak inputs from P3 to P7, "early phase" of CF synapse
      elimination from P7 to around P11, and "late phase" of CF synapse elimination
      from around P12. Normal PF-PC synapse formation is required for the "late phase"
      of CF synapse elimination.

PMID- 19166910
TI  - Intrinsic versus extrinsic determinants during the development of Purkinje cell
      dendrites.
AB  - The peculiar shape and disposition of Purkinje cell (PC) dendrites, planar and
      highly branched, offers an optimal model to analyze cellular and molecular
      regulators for the acquisition of neuronal dendritic trees. During the first 2
      weeks after the end of the proliferation period, PCs undergo a 2-phase remodeling
      process of their dendrites. The first phase consists in the complete retraction
      of the primitive but extensive dendritic tree, together with the formation of
      multiple filopodia-like processes arising from the cell body. In the second
      phase, there is a progressive disappearance of the somatic processes along with
      rapid growth and branching of the mature dendrite. Mature Purkinje cell dendrites
      bear two types of spiny protrusions, named spine and thorn. The spines are
      numerous, elongated, located at the distal dendritic compartment and form
      synapses with parallel fibers, whereas the thorns are shorter, rounded, emerge
      from the proximal compartment and synapse with climbing fibers. Different culture
      models and mutant mice analyses suggest the identification of intrinsic versus
      extrinsic determinants of the Purkinje cell dendritic development. The early
      phase of dendritic remodeling might be cell autonomous and regulated by specific
      transcription factors such as retinoid-related orphan receptor alpha (RORalpha).
      Afferent fibers, trophic factors and hormones regulate the orientation and growth
      of the mature dendritic tree contributing, with still unknown intrinsic factors,
      to sculpt its general architecture. The formation of spines appears as an
      intrinsic phenomenon independent of their presynaptic partner, the parallel
      fibers, and confined to the distal compartment by inhibitory influences of the
      climbing fibers along the proximal compartment.

PMID- 19166912
TI  - The medial amygdaloid nucleus modulates cardiovascular responses to acute
      restraint in rats.
AB  - The medial amygdaloid nucleus (MeA) modulates several physiological and
      behavioral processes and among them, the cardiovascular correlates of behavioral
      responses to stressful stimuli. Acute restraint evokes cardiovascular responses,
      which are characterized by both elevated blood pressure (BP) and intense heart
      rate (HR) increase. We presently report effects of MeA pharmacological
      manipulations on BP and HR responses evoked by acute restraint in rats. Bilateral
      microinjection of 100 nL of the unspecific synaptic blocker CoCl(2) (1 mM) into
      the MeA increased HR response to acute restraint, without significant effect on
      the BP response. This result indicates an inhibitory influence of MeA on
      restraint-evoked HR changes. Injections of the non-selective muscarinic receptor
      antagonist atropine (3 nmol); the inhibitor of choline uptake hemicholinium (2
      nmol) or the selective M(1)-receptor antagonist pirenzepine (6 nmol) caused
      effects that were similar to those caused by cobalt. These results suggest that
      local cholinergic neurotransmission and M(1)-receptors mediate the MeA inhibitory
      influence on restraint-related HR responses. Pretreatment with the M3 receptor
      antagonist 4-DAMP (4-Diphenylacetoxy-N-methylpiperidine methiodide-2 nmol) did
      not affect restraint-related cardiovascular responses, reinforcing the idea that
      M(1)-receptors mediate MeA-related inhibitory influence on restraint-evoked HR
      increase.

PMID- 19166911
TI  - Activation of toll-like receptor-3 induces interferon-lambda expression in human
      neuronal cells.
AB  - We examined the gene expression and regulation of type III human interferon
      (IFN), IFN-lambda, in human neuronal cells. Human neuronal cells expressed
      endogenous IFN-lambda1 but not IFN-lambda2/3. Upon the activation of Toll-like
      receptor (TLR)-3 expressed in the neuronal cells by polyriboinosinic
      polyribocytidylic acid (PolyI:C), both IFN-lambda1 and IFN-lambda2/3 expression
      was significantly induced. The activation of TLR-3 also exhibited antiviral
      activity against pseudotyped human immunodeficiency virus (HIV)-1 infection of
      the neuronal cells. Human neuronal cells also expressed functional IFN-lambda
      receptor complex, interleukin-28 receptor alpha subunit (IL-28Ralpha) and IL
      10Rbeta, as evidenced by the observations that exogenous IFN-lambda treatment
      inhibited pseudotyped HIV-1 infection of the neuronal cells and induced the
      expression of apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like
      (APOBEC)3G/3F, the newly identified anti-HIV-1 cellular factors. These data
      provide direct and compelling evidence that there is intracellular expression and
      regulation of IFN-lambda in human neuronal cells, which may have an important
      role in the innate neuronal protection against viral infections in the CNS.

PMID- 19166914
TI  - Epileptogenesis alters gene expression pattern in rats subjected to amygdala
      dependent emotional learning.
AB  - Here we tested a hypothesis that epileptogenesis influences expression pattern of
      genes in the basolateral amygdala that are critical for fear conditioning. Whole
      genome molecular profiling of basolateral rat amygdala was performed to compare
      the transcriptome changes underlying fear learning in epileptogenic and control
      animals. Our analysis revealed that after fear conditioning procedure 26 genes
      were regulated differently in the basolateral amygdala of both groups. Thus, our
      study provides the first evidence that not only the damage to the neuronal
      pathways but also altered composition or activity level of molecular machinery
      responsible for formation of emotional memories within surviving pathways can
      contribute to impairment in emotional learning in epileptogenic animals.
      Understanding the function of those genes in emotional learning provides an
      attractive avenue for identification of novel drug targets for treatment of
      emotional disorders after epileptogenesis-inducing insult.

PMID- 19166913
TI  - Mu-opioid and corticotropin-releasing-factor receptors show largely postsynaptic
      co-expression, and separate presynaptic distributions, in the mouse central
      amygdala and bed nucleus of the stria terminalis.
AB  - The anxiolytic effects of opiates active at the mu-opioid receptor (mu-OR) may be
      ascribed, in part, to suppression of neurons that are responsive to the stress
      associated peptide, corticotropin releasing factor (CRF), in the central amygdala
      (CeA) and bed nucleus of the stria terminalis (BNST). The corticotropin releasing
      factor receptor (CRFr) and mu-OR are expressed in both the CeA and BNST, but
      their subcellular relationship to each other is not known in either region. To
      address this question, we used dual electron microscopic immunolabeling of mu-OR
      and CRFr in the mouse lateral CeA and anterolateral BNST. Immunolabeling for each
      receptor was detected in the same as well as in separate somatic, dendritic and
      axonal profiles of neurons in each region. CRFr had a plasmalemmal or cytoplasmic
      distribution in many dendrites, including those co-expressing mu-OR. The co
      expression of CRFr and mu-OR also was seen near excitatory-type synapses on
      dendritic spines. In both the CeA and BNST, over 50% of the CRFr-labeled
      dendritic profiles (dendrites and spines) contained immunoreactivity for the mu
      OR. However, less than 25% of the dendritic profiles containing the mu-OR were
      labeled for CRFr in either region, suggesting that opiate activation of the mu-OR
      affects many neurons in addition to those responsive to CRF. The dendritic
      profiles containing CRFr and/or mu-OR received asymmetric, excitatory-type
      synapses from unlabeled or CRFr-labeled axon terminals. In contrast, the mu-OR
      was identified in terminals forming symmetric, inhibitory-type synapses. Thus, in
      both the CeA and BNST, mu-OR and CRFr have strategic locations for mediation of
      CRF and opioid effects on the postsynaptic excitability of single neurons, and on
      the respective presynaptic release of excitatory and inhibitory
      neurotransmitters. The commonalities in the synaptic location of both receptors
      in the CeA and BNST suggest that this is a fundamental cellular association of
      relevance to both drug addiction and stress-induced disorders.

PMID- 19166915
TI  - Estrogen impairs glucocorticoid dependent negative feedback on the hypothalamic
      pituitary-adrenal axis via estrogen receptor alpha within the hypothalamus.
AB  - Numerous studies have established a link between individuals with affective
      disorders and a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis,
      most notably characterized by a reduced sensitivity to glucocorticoid negative (
      ) feedback. Furthermore there is a sex difference in the etiology of mood
      disorders with incidence in females being two to three times that of males, an
      association that may be a result of the influence of estradiol (E2) on HPA axis
      function. In these studies, we have examined the effect of E2 on glucocorticoid
      mediated HPA axis (-) feedback during both the diurnal peak and the stress
      induced rise in corticosterone (CORT). Young adult female Sprague-Dawley (SD)
      rats were ovariectomized (OVX) and 1 week later treated subcutaneous (s.c.) with
      oil or estradiol benzoate (EB) for 4 days. On the 4th day of treatment, animals
      were injected with a single dose of dexamethasone (DEX), or vehicle. EB treatment
      significantly increased the evening elevation in CORT and the stress-induced rise
      in CORT. In contrast, DEX treatment reduced the diurnal and stress induced rise
      in CORT and adrenocorticotropic hormone (ACTH), and this reduction was not
      apparent following co-treatment with EB. To determine a potential site of E2's
      action, female SD rats were OVX and 1 week later, wax pellets containing E2, the
      estrogen receptor beta (ERbeta) agonist diarylpropionitrile (DPN), or the
      estrogen receptor alpha (ERalpha) agonist propylpyrazoletriol (PPT), was
      implanted bilaterally and dorsal to the paraventricular nucleus of the
      hypothalamus (PVN). Seven days later, animals were injected s.c. with a single
      dose of DEX, or vehicle to test for glucocorticoid-dependent (-) feedback.
      Results show that E2 and PPT increased, while DPN decreased the diurnal peak and
      stress-induced CORT and ACTH levels as compared to controls. Furthermore, E2 and
      PPT impaired the ability of DEX to inhibit both the diurnal and the stress
      induced rise in CORT and ACTH, whereas DPN had no effect. Neuronal activation was
      measured by c-fos mRNA expression within the PVN following restraint. E2 and PPT
      increased c-fos mRNA, and impaired the normal DEX suppression of neuronal
      activation in the PVN. Taken together, these data indicate that estradiol causes
      a dysregulation of HPA axis (-) feedback as evidenced by the inability of DEX to
      suppress diurnal and stress-induced CORT and ACTH secretion. Additionally, the
      ability of E2 to inhibit glucocorticoid (-) feedback occurs specifically via
      ERalpha acting at the level of the PVN.

PMID- 19166916
TI  - Thalidomide protects against ischemic neuronal damage induced by focal cerebral
      ischemia in mice.
AB  - We aimed to examine whether thalidomide might inhibit the neuronal damage
      resulting from focal cerebral ischemia, and if so to explore the neuroprotective
      mechanism. Focal cerebral ischemia was induced by permanent middle cerebral
      artery occlusion (MCAO) in mice, and thalidomide was intraperitoneally
      administered a total of three times (at 10 min before, just before, and 1 h after
      MCAO). Thalidomide significantly reduced (a) the infarct area and volume at 24
      and 72 h after MCAO and (b) the neurological score at 72 h after MCAO. Brains
      were also histochemically assessed for apoptosis and lipid peroxidation using
      terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)
      staining and an antibody recognizing 8-hydroxy-2'-deoxyguanosine (8-OHdG),
      respectively. Thalidomide reduced both the number of TUNEL-positive cells and the
      oxidative damage. However, post-treatment of thalidomide [20 mg/kg, three times
      (at just after, 1 h after, 3 h after MCAO)] did not reduce the infarct volume. In
      an in vitro study, we examined the effects of thalidomide on lipid peroxidation
      in mouse brain homogenates and on the production of various radical species.
      Thalidomide inhibited both the lipid peroxidation and the production of H(2)O(2)
      and O(2).(-) (but not HO(-)) radicals. We also measured the brain concentration
      of TNF-alpha by ELISA. The TNF-alpha level in the brain was significantly
      increased at 9-24 h after MCAO. However, thalidomide did not reduce the elevated
      TNF-alpha level at either 12 or 24 h after MCAO. These findings indicate that
      thalidomide has neuroprotective effects against ischemic neuronal damage in mice,
      and that an inhibitory action of thalidomide against oxidative stress may be
      partly responsible for these neuroprotective effects.

PMID- 19166917
TI  - Cocaine challenge enhances release of neuroprotective amino acid taurine in the
      striatum of chronic cocaine treated rats: a microdialysis study.
AB  - Drug addiction is a serious public health problem. There is increasing evidence
      on the involvement of augmented glutamatergic transmission in cocaine-induced
      addiction and neurotoxicity. We investigated effects of acute or chronic cocaine
      administration and cocaine challenge following chronic cocaine exposure on the
      release of excitotoxic glutamate and neuroprotective taurine in the rat striatum
      by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine
      exposure markedly increased the release of glutamate, which may cause
      neurotoxicity. Simultaneously, cocaine challenge after withdrawal also
      significantly increased the release of taurine, which counteracts glutamate
      mediated excitotoxicity and possibly cell death. Thus, the mammalian brain has an
      endogenous self-protective mechanism against cocaine-mediated neurotoxicity and
      potentially addiction.

PMID- 19166918
TI  - Effects of a hexane extract from Laurus novocanariensis leaves on the ethanol
      metabolism of Wistar rats.
AB  - A hexane extract from the leaves of Laurus novocanariensis was investigated for
      its activity on ethanol metabolism in Wistar rats. The extract could interfere
      with blood ethanol elevation, the induction of gastric alcohol dehydrogenase
      (ADH) and the reduction of erythrocyte catalase (CAT). The sesquiterpene lactones
      dehydrocostus lactone and costunolide were identified in the active extract, and
      might represent its active constituents. These results support the use of L.
      novocanariensis in the traditional Madeira Island medicine to protect against
      ethanol injury.

PMID- 19166919
TI  - Characterization and evolutionary landscape of AmnSINE1 in Amniota genomes.
AB  - Discovery of a large number of conserved non-coding elements (CNEs) in vertebrate
      genomes provides a cornerstone to elucidate molecular mechanisms of
      macroevolution. Extensive comparative genomics has proven that transposons such
      as short interspersed elements (SINEs) were an important source of CNEs. We
      recently characterized AmnSINE1, a SINE family in Amniota genomes, some of which
      are present in CNEs, and demonstrated that two AmnSINE1 loci play an important
      role in mammalian-specific brain development by functioning as an enhancer
      (Sasaki et al. Proc. Natl. Acad. Sci. USA 2008). To get more information about
      AmnSINE1s, we here performed a multi-species search for AmnSINE1, and revealed
      the distribution and evolutionary history of these SINEs in amniote genomes. The
      number of AmnSINE1 regions in amniotes ranged from 160 to 1200; the number in the
      eutherians were under 500 and the largest was that in chicken. Phylogenetic
      analysis established that each AmnSINE1 locus has evolved uniquely, primarily
      since the divergence of mammals from reptiles. These results support the notion
      that AmnSINE1s were amplified as an ancient retroposon in a common ancestor of
      Amniota and subsequently have survived for 300 Myr because of functions acquired
      by mutation-coupled exaptation prior mammalian radiation. On the basis of
      sequence homology and conserved synteny, we detected the orthologs of AmnSINE1
      for candidates of further enhancer analysis, which are more conserved than two
      loci that were shown to have been involved in mammalian brain development. The
      present work provides a comprehensive data set to test the role of AmnSINE1s,
      many of which were exapted and contributed to mammalian macroevolution.

PMID- 19166920
TI  - A novel administration route for edaravone: I. Effects of metabolic inhibitors on
      skin permeability of edaravone.
AB  - We examined the effects of metabolic inhibitors on skin permeation of edaravone.
      SKF-525A, diclofenac sodium (DIC) and indomethacin (IND) were added to
      supernatant fluid (SF) of hairless rat (HR) skin homogenate. L-Cysteine (L-Cys)
      and benzotriazole (BTA), as pharmaceutical additives, were added to HR skin
      homogenate SF, and incubated at 37 degrees C for 30 min. K(m) and V(max) values
      were calculated. For determination of edaravone skin permeation from
      edaravone/hydroxypropyl-beta-cyclodextrin (HPbetaCD) complex solution, HR skin
      was placed in a Franz diffusion cell, and kept at 37 degrees C.
      Edaravone/HPbetaCD solution that contained L-Cys was put into the donor side. The
      relative activity in skin homogenate SF after co-treatment with IND and SKF-525A
      decreased to 40.8% of the control. However, DIC and IND had a weak inhibitory
      effect. For inhibition of edaravone metabolism, L-Cys and BTA had no effect on
      K(m) value, but V(max) was significantly decreased compared with controls
      (*P<0.05, Tukey-Kramer test). The edaravone skin permeation rate and permeability
      coefficient from edaravone/HPbetaCD complex solution with inhibitor were
      significantly increased compared with those without inhibitor. We suggest that
      the metabolism inhibitor was useful for the transdermal delivery of edaravone.

PMID- 19166921
TI  - Effects of alternating current frequency and permeation enhancers upon human
      epidermal membrane.
AB  - Previous studies have demonstrated the ability of AC iontophoresis to control
      skin resistance in different transdermal iontophoresis applications. The
      objectives of the present study were to (a) identify the alternating current (AC)
      frequency for the optimization of AC pore induction of human epidermal membrane
      (HEM) and (b) determine the effects of chemical permeation enhancers upon the
      extent of pore induction under AC conditions. Experiments with a synthetic
      membrane system were first conducted as the control. In these synthetic membrane
      experiments, the electrical resistance of the membrane remained essentially
      constant, suggesting constant electromobility of the background electrolyte ions
      under the AC conditions studied. In the HEM experiments, the electrical
      resistance data showed that higher applied voltages were required to induce the
      same extent of pore induction in HEM at AC frequency of 1kHz compared with those
      at 30Hz. Even higher voltages were needed at AC frequencies of 10kHz and higher.
      AC frequency also influenced the recovery of HEM electrical resistance after AC
      iontophoresis application. An optimal AC frequency region for effective pore
      induction and least sensation was proposed. Permeation enhancers were shown to
      enhance pore induction in HEM during AC iontophoresis. The enhancers reversibly
      reduced the AC voltage required to sustain a constant state of pore induction in
      HEM during AC iontophoresis, consistent with the mechanism of lipid lamellae
      electroporation in the stratum corneum.

PMID- 19166922
TI  - Stimuli-responsive antioxidant nanoprodrugs of NSAIDs.
AB  - A novel group of alpha-lipoic acid-containing hydrophobic prodrugs of non
      steroidal anti-inflammatory drugs (NSAIDs) was synthesized and transformed into
      nanometer-sized prodrugs (nanoprodrugs). Three NSAIDs, indomethacin, ibuprofen
      and naproxen were linked to alpha-lipoic acid via tetraethylene glycol through
      hydrolytically degradable ester bonds. The three bifunctional derivatives were
      dissolved in organic solvents and capable of forming stable nanoprodrugs upon
      addition of the organic solutions into aqueous phase through the spontaneous
      emulsification mechanism. Antioxidant property and stimuli-responsiveness of the
      nanoprodrugs were demonstrated by hypochlorous acid (HOCl) scavenging followed by
      oxidative destabilization of the nanoprodrugs. The effect of varying NSAIDs on
      the in vitro hydrolytic prodrug activation catalyzed by porcine liver esterase
      was investigated by monitoring the rates of NSAIDs hydrolysis from the
      nanoprodrugs. The remarkable feature of these nanoprodrugs is that despite the
      highly hydrophobic nature of the derivatives NSAIDs were readily hydrolyzed
      enzymatically from the nanoprodrugs. Furthermore, the rate of hydrolysis was
      higher when the nanoprodrugs were oxidized and destabilized upon HOCl scavenging
      suggesting an enhanced activation of the nanoprodrugs in the oxidative
      environment.

PMID- 19166923
TI  - 9-NC-loaded folate-conjugated polymer micelles as tumor targeted drug delivery
      system: preparation and evaluation in vitro.
AB  - In this study, folate-conjugated polymer micelles were synthesized by mixing
      folate-poly(ethylene glycol)-distearoylphosphatidylethanolamine (FA-PEG-DSPE) and
      methoxy-poly(ethylene glycol)-distearoylphosphatidylethanolamine (MPEG-DSPE) to
      encapsulate anticancer agent 9-nitro-camptothecin (9-NC). Formulations were
      characterized by critical micellization concentration (CMC) values of copolymers,
      micelle particle size, zeta-potential, encapsulation efficiency and drug loading
      efficiency. The molar ratio of FA-PEG-DSPE and MPEG-DSPE was chosen to avoid the
      macrophages and at the same time express highly active targeting ability. The
      targeting ability of folate-conjugated polymer micelles was investigated against
      three kinds of tumor cell lines (HeLa, SGC7901 and BXPC3). The drug efficacy in
      vitro of folate-conjugated polymer micelles was evaluated by using the
      methylthiazoletetrazolium (MTT) method. The results showed that the CMC values of
      MPEG-DSPE and FA-PEG-DSPE were 0.97 x 10(-5)M and 1.0 x 10(-5)M, respectively.
      The average size of folate-conjugated micelle was about 21-24 nm and the micelle
      size distribution of both empty and drug-loaded micelles were rather narrow. The
      encapsulation efficiency and drug loading efficiency were 97.6% and 4.64%,
      respectively. The drug-loaded micelles were stable during storage at 4 degrees C
      for 4 weeks. Micelles maintain the similar size and did not show 9-NC leakage.
      The best molar ratio of FA-PEG-DSPE and MPEG-DSPE in folate-conjugated micelles
      was 1:100 which can effectively solubilize 9-NC, avoid the macrophages in vitro
      and has a higher anti-tumor activity than both drug-loaded MPEG-DSPE micelles and
      free anticancer agents. The folate-conjugated polymer micelle which can avoid the
      macrophages is a kind of promising carrier for poorly soluble anticancer agents
      via folate receptor (FR) that mediated endocytosis to target tumor cells.

PMID- 19166924
TI  - Medium- and high-throughput screening of neurotoxicants using C. elegans.
AB  - The U.S. National Toxicology Program, the U.S. Environmental Protection Agency,
      and other national and international agencies are committing significant
      resources towards the development of alternative species to be used as
      replacements for mammalian models in toxicological studies. Caenorhabditis
      elegans is a well-characterized soil nematode that is becoming a useful model in
      the assessment of neurotoxicants. To determine the effects of potential
      neurotoxicants on C. elegans, four medium-throughput (feeding, growth,
      reproduction and locomotion) and two high-throughput (growth and reproduction)
      assays have been developed. Three of these assays use the COPAS Biosort, a flow
      cytometer capable of rapidly measuring thousands of nematodes in minutes. Medium
      throughput feeding, growth, and reproduction assays were used to assess the
      toxicity of eight suspected neurotoxicants. For several of the neurotoxicants
      examined, significant effects were observed at similar concentrations between
      assays. High-throughput reproduction and growth assays were used to estimate the
      toxicity of thousands of chemicals in two libraries. These assays will prove
      useful in evaluating the role of alternative toxicological models in tiered
      toxicity testing of thousands of chemicals.

PMID- 19166925
TI  - PKA-induced F-actin rearrangement requires phosphorylation of Hsp27 by the MAPKAP
      kinase MK5.
AB  - Mitogen-activated protein kinase (MAPK) pathways can play a role in F-actin
      dynamics. In particular, the p38 MAPK/MAPK-activated protein kinase 2 (MK2)/heat
      shock protein 27 (Hsp27) pathway is involved in F-actin alternations. Previously,
      we showed that MK5 is implicated in F-actin rearrangement induced by the
      cAMP/cAMP-dependent protein kinase pathway in PC12 cells, while others found
      Hsp27 to be a good in vitro MK5 substrate. Here we demonstrate that MK5 can
      specifically interact with Hsp27 in vivo and can induce phosphorylation at serine
      residues 78 and 82 in cells. siRNA-mediated depletion of Hsp27 protein levels, as
      well as overexpression of the non-phosphorylatable Hsp27-3A mutant prevented
      forskolin-induced F-actin reorganization. While ectopic expression of a
      constitutive active MK5 mutant was sufficient to induce F-actin rearrangement in
      PC12 cells, co-expression of Hsp27-3A could ablate this process. Our results
      imply that MK5 is involved in Hsp27-controlled F-actin dynamics in response to
      activation of the cAMP-dependent protein kinase pathway. These findings render
      the MK5/Hsp27 connection into a putative therapeutic target for conditions with
      aberrant Hsp27 phosphorylation such as metastasis, cardiovascular diseases,
      muscle atrophy, autoimmune skin disease and neuropathology.

PMID- 19166926
TI  - Regulation of IRAK-1 activation by its C-terminal domain.
AB  - Macrophages are important mediators of the immune response to infection by virtue
      of their ability to secrete cytokines that trigger inflammation. Toll-like
      receptors (TLRs) are largely responsible for meditating the activation of
      macrophages by pathogens. IRAK-1 is a proximal protein kinase in TLR signalling
      pathways and hence its activation must be tightly regulated. However, the
      mechanisms which control the activation of IRAK-1 are poorly understood. IRAK-1
      contains a death domain at its N-terminus that mediates its interaction with
      other death domain containing proteins, a central Ser/Thr kinase domain, and a C
      terminal domain that contains binding motifs for TRAF6. We show here that
      deletion of the death domain or the majority of the C-terminal domain markedly
      enhanced the capacity of IRAK-1 to activate NF-kappaB in a TLR-independent manner
      in RAW 264.7 macrophages. Furthermore, the C-terminal truncation mutant
      spontaneously oligomerised and formed complexes with the negative regulator IRAK
      M in the absence of TLR activation. In contrast to the binding of IRAK-M to IRAK
      1, the death domain of IRAK-1 was not required for the interaction of IRAK-4 with
      IRAK-1. On the basis of these results we propose a model in which IRAK-1 is held
      in a closed, inactive conformation via an intramolecular mechanism involving its
      C-terminal domain and possibly the death domain. Phosphorylation of IRAK-1 by
      IRAK-4 in response to TLR activation may then release IRAK-1 from the inhibitory
      constraint exerted by its C-terminal domain.

PMID- 19166927
TI  - Intersectin 1 forms a complex with adaptor protein Ruk/CIN85 in vivo
      independently of epidermal growth factor stimulation.
AB  - Intersectin 1 (ITSN1) is an adaptor protein involved in clathrin-mediated
      endocytosis, apoptosis, signal transduction and cytoskeleton organization. Here,
      we show that ITSN1 forms a complex with adaptor protein Ruk/CIN85, implicated in
      downregulation of receptor tyrosine kinases. The interaction is mediated by the
      SH3A domain of ITSN1 and the third or fourth proline-rich blocks of Ruk/CIN85,
      and does not depend on epidermal growth factor stimulation, suggesting a
      constitutive association of ITSN1 with Ruk/CIN85. Moreover, both proteins
      colocalize in MCF-7 cells with their common binding partner, the ubiquitin ligase
      c-Cbl. The possible biological role of the interaction between ITSN1 and
      Ruk/CIN85 is discussed.

PMID- 19166929
TI  - Mammalian target of rapamycin complex 1: signalling inputs, substrates and
      feedback mechanisms.
AB  - The mammalian target of rapamycin (mTOR) signalling pathway is implicated in the
      pathogenesis of a number of cancers and inherited hamartoma syndromes which have
      led to mTOR inhibitors, such as rapamycin, being tested in clinical trials.
      Knowledge of the mTOR pathway is rapidly expanding. This review provides an
      update on the most recent additions to the mTOR pathway with particular emphasis
      on mTORC1 signalling. mTORC1 signalling is classically known for its role in
      regulating cell growth and proliferation through modulation of protein synthesis.
      Recent research has identified novel mTORC1 cell signalling mechanisms that
      modulate mitochondrial biogenesis, hypoxia signalling and cell cycle progression
      and uncovered novel mTORC1 targets; YY1, HIF and SGK1. It is unsurprising that
      regulation of mTORC1 is multifaceted with many positive and negative signalling
      inputs. We discuss the recent advances that have been made to determine the
      upstream mechanisms that control mTORC1 through hypoxia, energy sensing and
      nutrient signalling. Also discussed are current findings that have unravelled a
      series of novel mTORC1-associated proteins that directly control the activity of
      mTORC1 and include PRAS40, FKBP38, Rag GTPases and RalA.

PMID- 19166930
TI  - Adrenomedullin promotes cell cycle transit and up-regulates cyclin D1 protein
      level in human glioblastoma cells through the activation of c-Jun/JNK/AP-1 signal
      transduction pathway.
AB  - Adrenomedullin is a secreted peptide hormone with multiple functions. Although a
      number of reports have indicated that adrenomedullin may be involved in tumor
      progression, its mechanism of action remains obscure. In this study, we have
      analysed the signal transduction pathway activated by adrenomedullin in human
      glioma cells. Our results revealed that adrenomedullin induced the
      phosphorylation of both c-Jun and JNK in glioblastoma cells. Silencing JNK
      expression with siRNA reversed the phosphorylation of c-Jun induced by
      adrenomedullin, indicating that JNK is responsible of c-Jun activation. In
      addition, electrophoretic mobility-shift assays showed that the increase in
      phosphorylation of c-Jun was associated with increased AP-1 DNA binding activity.
      Supershift assays and co-immunoprecipitation demonstrated that c-Jun and JunD are
      part of the AP-1 complex, indicating that activated c-Jun is dimerized with JunD
      in response to adrenomedullin. Furthermore, adrenomedullin was shown to promote
      cell transit beyond cell cycle phases with a concomittant increase in cyclin D1
      protein level, suggesting that adrenomedullin effects cell proliferation through
      up-regulation of cyclin D1. The inhibition of JNK activation or the suppression
      of c-Jun or JunD expression with siRNA impaired the effects of adrenomedullin on
      cell proliferation and on cyclin D1. Taken together, these data demonstrate that
      activation of cJun/JNK pathway is involved in the growth regulatory activity of
      adrenomedullin in glioblastoma cells.

PMID- 19166928
TI  - Gastrointestinal growth factors and hormones have divergent effects on Akt
      activation.
AB  - Akt is a central regulator of apoptosis, cell growth and survival. Growth factors
      and some G-protein-coupled receptors (GPCR) regulate Akt. Whereas growth-factor
      activation of Akt has been extensively studied, the regulation of Akt by GPCR's,
      especially gastrointestinal hormones/neurotransmitters, remains unclear. To
      address this area, in this study the effects of GI growth factors and
      hormones/neurotransmitters were investigated in rat pancreatic acinar cells which
      are high responsive to these agents. Pancreatic acini expressed Akt and 5 of 7
      known pancreatic growth-factors stimulate Akt phosphorylation (T308, S473) and
      translocation. These effects are mediated by p85 phosphorylation and activation
      of PI3K. GI hormones increasing intracellular cAMP had similar effects. However,
      GI-hormones/neurotransmitters [CCK, bombesin, carbachol] activating phospholipase
      C (PLC) inhibited basal and growth-factor-stimulated Akt activation. Detailed
      studies with CCK, which has both physiological and pathophysiological effects on
      pancreatic acinar cells at different concentrations, demonstrated CCK has a
      biphasic effect: at low concentrations (pM) stimulating Akt by a Src-dependent
      mechanism and at higher concentrations (nM) inhibited basal and stimulated Akt
      translocation, phosphorylation and activation, by de-phosphorylating p85
      resulting in decreasing PI3K activity. This effect required activation of both
      limbs of the PLC-pathway and a protein tyrosine phosphatase, but was not mediated
      by p44/42 MAPK, Src or activation of a serine phosphatase. Akt inhibition by CCK
      was also found in vivo and in Panc-1 cancer cells where it inhibited serum
      mediated rescue from apoptosis. These results demonstrate that GI growth factors
      as well as gastrointestinal hormones/neurotransmitters with different cellular
      basis of action can all regulate Akt phosphorylation in pancreatic acinar cells.
      This regulation is complex with phospholipase C agents such as CCK, because both
      stimulatory and inhibitory effects can be seen, which are mediated by different
      mechanisms.

PMID- 19166932
TI  - Clusterin silencing in human lung adenocarcinoma cells induces a mesenchymal-to
      epithelial transition through modulating the ERK/Slug pathway.
AB  - The ubiquitously expressed glycoprotein Clusterin (CLU) is implicated in diverse
      cellular processes, yet its genuine molecular function remains undefined. CLU
      expression has been associated with various human malignancies, yet the
      mechanisms by which CLU promotes cancer progression and metastasis are not
      elucidated. In this study, using human lung adenocarcinoma cell lines as a model,
      we explored the involvement of CLU in modulating invasiveness of cancer cells. We
      discovered that CLU levels positively correlated with the degree of invasiveness
      in human lung adenocarcinoma cell lines. The observation that CLU-rich cells
      displayed a spindle-shape morphology while those with low CLU levels were
      cuboidal in shape prompted us to investigate if CLU modulates epithelial-to
      mesenchymal transitions (EMT). CLU silencing by siRNA in a highly invasive, CLU
      rich lung adenocarcinoma cell line induced a mesenchymal-to-epithelial transition
      (MET) evidenced by the spindle-to-cuboidal morphological change, increased E
      cadherin expression, and decreased fibronectin expression. Compared with the
      vector-transfected cells, CLU-knocked-down (CLUi) cells showed reduced migration
      and invasion in vitro, as well as decreased metastatic potential in experimental
      metastasis. Re-expression of CLU in CLUi cells reversed the MET and restored the
      mesenchymal and invasive phenotypes. We found that Slug, a zinc-finger-containing
      transcriptional repressor of E-cadherin, was downregulated in CLUi cells. We also
      discovered that levels of activated ERK correlated with those of CLU and Slug.
      Taken together, our data suggest that CLU may regulate EMT and aggressive
      behaviour of human lung adenocarcinoma cells through modulating ERK signalling
      and Slug expression.

PMID- 19166931
TI  - Akt-dependent and -independent mechanisms of mTOR regulation in cancer.
AB  - The protein kinase mTOR (mammalian target of rapamycin) is a critical regulator
      of cellular metabolism, growth, and proliferation. These processes contribute to
      tumor formation, and many cancers are characterized by aberrant activation of
      mTOR. Although activating mutations in mTOR itself have not been identified,
      deregulation of upstream components that regulate mTOR are prevalent in cancer.
      The prototypic mechanism of mTOR regulation in cells is through activation of the
      PI3K/Akt pathway, but mTOR receives input from multiple signaling pathways. This
      review will discuss Akt-dependent and -independent mechanisms of mTOR regulation
      in response to mitogenic signals, as well as its regulation in response to energy
      and nutrient-sensing pathways. Preclinical and clinical studies have demonstrated
      that tumors bearing genetic alterations that activate mTOR are sensitive to
      pharmacologic inhibition of mTOR. Elucidation of novel pathways that regulate
      mTOR may help identify predictive factors for sensitivity to mTOR inhibitors, and
      could provide new therapeutic targets for inhibiting the mTOR pathway in cancer.
      This review will also highlight pharmacologic approaches that inhibit mTOR via
      activation of the AMP-activated protein kinase (AMPK), an important inhibitor of
      the mTOR pathway and an emerging target in cancer.

PMID- 19166933
TI  - Interleukin-1 regulates keratinocyte expression of T cell targeting chemokines
      through interleukin-1 receptor associated kinase-1 (IRAK1) dependent and
      independent pathways.
AB  - IL-1 is a potent pro-inflammatory cytokine that activates intracellular signaling
      cascades some of which may involve IL-1 receptor associated kinase-1 (IRAK1).
      Psoriasis is a T cell dependent chronic inflammatory condition of the skin of
      unknown cause. IL-1 has been implicated in psoriasis pathology, but the mechanism
      has not been elucidated. Interestingly, expression of IRAK1 is elevated in
      psoriatic skin. To identify a potential link between IL-1, keratinocytes and T
      cells in skin inflammation we employed pathway-focused microarrays to evaluate IL
      1 dependent gene expression in keratinocytes. Several candidate mRNAs encoding
      known T cell chemoattractants were identified in primary keratinocytes and the
      stable keratinocyte cell line HaCaT. CCL5 and CCL20 mRNA and protein levels were
      confirmed up-regulated by IL-1 in concentration and time-dependent manners.
      Furthermore IL-1 synergized with IFN-gamma and TNF-alpha. Expression of CXCL9,
      CXCL10 and CXCL11 mRNAs was also increased in response to IL-1, but protein could
      only be detected in medium from cells treated with IFN-gamma alone or in
      combination with IL-1. Over-expression of IRAK1 led to increased constitutive and
      cytokine induced production of CCL5 and CCL20. Inhibition of IRAK1 activity
      through RNAi or expression of a dominant negative mutant blocked production of
      CCL5 and CCL20 but had no effect upon the IL-1 enhancement of IFN-gamma induced
      CXCL9, CXCL10 and CXCL11 production. In conclusion IL-1 regulates T cell
      targeting chemokine production in keratinocytes through IRAK1 dependent and
      independent pathways. These pathways may contribute to acute and chronic skin
      inflammation.

PMID- 19166934
TI  - Differential regulation of transferrin 1 and 2 in Aedes aegypti.
AB  - Available evidence has shown that transferrins are involved in iron metabolism,
      immunity and development in eukaryotic organisms including insects. Here we
      characterize the gene and message expression profile of Aedes aegypti transferrin
      2 (AaTf2) in response to iron, bacterial challenge and life stage. We show that
      AaTf2 shares a low similarity with A. aegypti transferrin 1 (AaTf1), but higher
      similarity with mammalian transferrins and avian ovotransferrin. Iron-binding
      pocket analysis indicates that AaTf2 has residue substitutions of Y188F, T120S,
      and R124S in the N lobe, and Y517N, H585N, T452S, and R456T in the C lobe, which
      could alter or reduce iron-binding activity. In vivo studies of message
      expression reveal that AaTf2 message is expressed at higher levels in larva and
      pupa, as well as adult female ovaries 72h post blood meal (PBM) and support that
      AaTf2 could play a role in larval and pupal development and in late physiological
      events of the gonotrophic cycle. Bacterial challenge significantly increases
      AaTf1 expression in ovaries at 0 and 24h PBM, but decreases AaTf2 expression in
      ovaries at 72h PBM, suggesting that AaTf1 and AaTf2 play different roles in
      immunity of female adults during a gonotrophic cycle.

PMID- 19166935
TI  - Analysis of indirect pathway CD4+ T cells in a patient with metastable tolerance
      to a kidney allograft: possible relevance to superior graft survival of HLA class
      II closely matched renal allografts.
AB  - MHC class I mismatched, but class II matched kidney transplants are tolerogenic
      in large animal models. CD4(+) T regulatory cells specific for HLA-B1501-derived
      peptide p37-MA (DSDAASPRMAPRAPWIEQ) developed in a long term (>12 years) tolerant
      patient who received an HLA-B1501 mismatched, HLA class II closely matched renal
      allograft. We hypothesized that class II matching favored T regulatory cell
      development by allowing allopeptide presentation on either recipient (DR4/DQ7(+))
      or donor (DR4/DQ8(+)) antigen presenting cells (APC). Indirect pathway CD4(+) T
      cell clones were generated from recipient PBMC by sorting antigen-stimulated,
      proliferating cells. Most clones responded to p37-MA-pulsed B1501(-) autologous,
      but not to DQ8(+)B1501(+) donor B-lymphoblastoid cell lines (B-LCL). However,
      some clones responded to both; in fact, one responded even more strongly to donor
      B-LCL than to p37-MA-pulsed autologous B-LCL. P37-MA contained a DQ8-binding
      motif and induced strong TH1 responses from DQ8 but not DQ6 transgenic mice.
      Microchimerism was found to be enriched in the dendritic cells (DC) cultured from
      adherent PBMC. This indicates donor APC could possibly present p37-MA peptide
      directly to p37-MA specific T cells. These data support the concept that, when
      the donor is MHC class II closely matched, a "hybrid" form of allorecognition
      (direct/indirect) occurs. This may favor the generation of a beneficial form of
      indirect pathway alloreactivity, i.e. allopeptide-specific CD4(+) T regulatory
      cells, in the context of long term DC microchimerism.

PMID- 19166936
TI  - Chronic humoral rejection mediated by anti-HLA-DP alloantibodies: insights into
      the role of epitope sharing in donor-specific and non-donor specific
      alloantibodies generation.
AB  - We report the case of a renal transplanted patient, in whom the detection of a
      unique anti HLA-DP antibody response preceded the development of chronic humoral
      rejection. In addition to donor-specific anti-DP alloantibodies, the patient
      displayed reactions against several non-donor-specific DP antigens (NDSA).
      Interestingly, we found that all the DP molecules recognized by the
      alloantibodies displayed the same amino-acid sequence suggesting that epitope
      sharing between unrelated HLA molecules was the mechanism underlying NDSA
      generation. This case highlights the pathogenicity of anti-DP alloantibodies and
      suggests that it could be more meaningful to match the epitopes than the HLA
      antigens for the prevention of rejection.

PMID- 19166937
TI  - Early inhibition of HIF-1alpha with small interfering RNA reduces ischemic
      reperfused brain injury in rats.
AB  - Hypoxia-inducible factor-1 (HIF-1) plays an essential role in cerebral ischemia
      as a proapoptotic factor. We hypothesized that HIF-1alpha siRNA can protect the
      brain from ischemic damage by inhibiting HIF-1alpha induced apoptotic pathway at
      the RNA level in a rat focal ischemic model. Results showed that treatment with
      HIF-1alpha siRNA reduced the infarct volume, decreased mortality, improved
      neurological deficits and reduced Evans blue extravasation. The expression of HIF
      1alpha mRNA (Real-Time PCR) and protein were significantly silenced and the
      immunohistochemistry and Western blot revealed the suppression of HIF-1alpha,
      VEGF, p53 and Caspase-3. Double fluorescence labeling showed HIF-1alpha positive
      immunoreactive materials were partly colocalized with NeuN, p53 and Caspase-3 in
      the injured cerebral cortex. This study showed that HIF-1alpha siRNA may protect
      the ischemic-reperfused neurons in vivo via inhibition of HIF-1alpha, its
      downstream VEGF and other apoptotic-related proteins such as p53 and Caspase-3
      and may have potentials for the early treatment of ischemic cerebral stroke.

PMID- 19166938
TI  - JNK regulates APP cleavage and degradation in a model of Alzheimer's disease.
AB  - Secretion of Amyloid-beta peptide (Abeta) circulating oligomers and their
      aggregate forms derived by processing of beta-amyloid precursor protein (APP) are
      a key event in Alzheimer's disease (AD). We show that phosphorylation of APP on
      threonine 668 may play a role in APP metabolism in H4-APP(sw) cell line, a
      degenerative AD model. We proved that JNK plays a fundamental role in this
      phosphorylation since its specific inhibition, with the JNK inhibitor peptide (D
      JNKI1), induced APP degradation and prevented APP phosphorylation at T668. This
      results in a significant drop of betaAPPs, Abeta fragments and Abeta circulating
      oligomers. Moreover the D-JNKI1 treatment produced a switch in the APP
      metabolism, since the peptide reduced the rate of the amyloidogenic processing in
      favour of the non-amyloidogenic one. All together our results suggest an
      important link between APP metabolism and the JNK pathway and contribute to shed
      light on the molecular signalling pathway of this disease indicating JNK as an
      innovative target for AD therapy.

PMID- 19166940
TI  - Development of stable isotope and selenomethionine labeling methods for proteins
      expressed in Pseudomonas fluorescens.
AB  - Pseudomonas fluorescens is a robust protein expression system that is very well
      suited for high throughput protein expression for structural genomics studies.
      Since NMR spectroscopy and X-ray crystallography are both used by various
      investigators in structure elucidation studies, the availability of target
      proteins labeled with stable isotopes or selenomethionine is essential for the
      determination of protein structures. A completely defined medium for the
      expression and stable isotope labeling of proteins in P. fluorescens has been
      developed. The expression level of Bacillus thuringiensis Cry34 in the modified
      medium is comparable to that obtained in the original medium. In addition, more
      than 95% incorporation of 15N was obtained in Cry34 using 15N ammonium sulfate
      and the quality of the protein, as assessed by NMR analysis, is comparable to
      that made using commercial medium. High levels of selenomethionine (SeMet)
      incorporation in the Xenorhabdus nematophilus insecticidal protein XptA2 were
      also obtained in P. fluorescens using the defined medium, allowing development of
      a method for obtaining highly purified XptA2. The following observations were
      made when inhibitors of endogenous methionine biosynthesis were used in P.
      fluorescens culture when SeMet was substituted in XptA2: (I) there is little
      inhibition of cell growth or recombinant XptA2 expression in the presence of
      SeMet concentrations up to 300 mg/L in cell culture, (II) there was greater than
      95% SeMet incorporation ratio in recombinant SeMet-labeled XptA2 (SeMet-XptA2)
      and the incorporation ratio is consistent and reproducible and (III) finally,
      purified SeMet-XptA2 possesses similar protein structure and insecticidal
      activity relative to the unlabeled counterpart XptA2 as shown by bioassay and
      differential scanning calorimetric analysis. The high SeMet incorporation should
      provide high accuracy and resolution in XptA2 phase determination by
      multiwavelength anomalous diffraction (MAD), indicating that P. fluorescens is an
      excellent expression host to produce SeMet-labeled proteins for structural study.

PMID- 19166939
TI  - Endogenous angiotensin-(1-7) reduces cardiac ischemia-induced dysfunction in
      diabetic hypertensive rats.
AB  - Angiotensin-(1-7) [Ang-(1-7)] is a vasodilator peptide with cardiac and vascular
      protective properties. We examined the influence of Ang-(1-7), both endogenous
      and after chronic treatment with the peptide (576microg/(kgday)), on
      ischemia/reperfusion (I/R)-induced cardiac dysfunction in streptozotocin-treated
      spontaneously hypertensive rats (diabetic SHR). In isolated perfused hearts,
      recovery of left ventricular function from 40min of global ischemia was improved
      significantly in Ang-(1-7)- or captopril-treated diabetic SHR and worsened in
      animals treated with A779, an Ang-(1-7) receptor (AT((1-7))) antagonist. The
      beneficial effect of captopril on cardiac recovery was reduced when co
      administered with A779. Cardiac NF-kappaB activity appears to be higher in
      diabetic SHR and treatment with Ang-(1-7) or captopril decreased NF-kappaB
      activity in diabetic SHR, an effect partially reversed by co-administration of
      A779. Real-time PCR-based gene array analysis of cardiac tissue revealed that Ang
      (1-7) or captopril treatment may reduce expression of several genes of
      inflammation involved in the NF-kappaB signalling pathway. The data provide for
      the first time a role for endogenous Ang-(1-7) as well as confirmation that
      exogenous treatment with the peptide produces cardioprotection. Whether potential
      anti-inflammatory and transcriptional factor changes are directly linked to the
      cardioprotection produced by Ang-(1-7) in diabetic SHR remains to be determined.

PMID- 19166942
TI  - Measuring fMRI reliability with the intra-class correlation coefficient.
AB  - The intra-class class correlation coefficient (ICC) is a prominent statistic to
      measure test-retest reliability of fMRI data. It can be used to address the
      question of whether regions of high group activation in a first scan session will
      show preserved subject differentiability in a second session. With this purpose,
      we present a method that extends voxel-wise ICC analysis. We show that voxels
      with high group activation have more probability of being reliable, if a
      subsequent session is performed, than typical voxels across the brain or across
      white matter. We also find that the existence of some voxels with high ICC but
      low group activation can be explained by stable signals across sessions that
      poorly fit the HRF model. At a region of interest level, we show that our voxel
      wise ICC calculation is more robust than previous implementations under
      variations of smoothing and cluster size. The method also allows formal
      comparisons between the reliabilities of given brain regions; aimed at
      establishing which ROIs discriminate best between individuals. The method is
      applied to an auditory and a verbal working memory task. A reliability toolbox
      for SPM5 is provided at http://brainmap.co.uk.

PMID- 19166941
TI  - A method for the alignment of heterogeneous macromolecules from electron
      microscopy.
AB  - We propose a feature-based image alignment method for single-particle electron
      microscopy that is able to accommodate various similarity scoring functions while
      efficiently sampling the two-dimensional transformational space. We use this
      image alignment method to evaluate the performance of a scoring function that is
      based on the Mutual Information (MI) of two images rather than one that is based
      on the cross-correlation function. We show that alignment using MI for the
      scoring function has far less model-dependent bias than is found with cross
      correlation based alignment. We also demonstrate that MI improves the alignment
      of some types of heterogeneous data, provided that the signal-to-noise ratio is
      relatively high. These results indicate, therefore, that use of MI as the scoring
      function is well suited for the alignment of class-averages computed from single
      particle images. Our method is tested on data from three model structures and one
      real dataset.

PMID- 19166943
TI  - Imaging the impossible: an fMRI study of impossible causal relationships in magic
      tricks.
AB  - Understanding causal relationships and violations of those relationships is
      fundamental to learning about the world around us. Over time some of these
      relationships become so firmly established that they form part of an implicit
      belief system about what is possible and impossible in the world. Previous
      studies investigating the neural correlates of violations of learned
      relationships have focused on relationships that were task-specific and
      probabilistic. In contrast, the present study uses magic-trick perception as a
      means of investigating violations of relationships that are long-established,
      deterministic, and that form part of the aforementioned belief system. Compared
      to situations in which expected causal relationships are observed, magic trick
      perception recruited dorso-lateral prefrontal cortex (DLPFC) and anterior
      cingulate cortex (ACC), brain regions associated with the detection of conflict
      and the implementation of cognitive control. These activations were greater in
      the left hemisphere, supporting a role for this hemisphere in the interpretation
      of complex events. DLPFC is more greatly activated by magic tricks than by
      surprising events, but not more greatly activated by surprising than non
      surprising events, suggesting that this region plays a special role in causality
      processing. The results suggest a role for cognitive control regions in the left
      hemisphere in a neurobiology of disbelief.

PMID- 19166944
TI  - Meta-analysis of neuroimaging data: a comparison of image-based and coordinate
      based pooling of studies.
AB  - With the rapid growth of neuroimaging research and accumulation of
      neuroinformatic databases the synthesis of consensus findings using meta-analysis
      is becoming increasingly important. Meta-analyses pool data across many studies
      to identify reliable experimental effects and characterize the degree of
      agreement across studies. Coordinate-based meta-analysis (CBMA) methods are the
      standard approach, where each study entered into the meta-analysis has been
      summarized using only the (x, y, z) locations of peak activations (with or
      without activation magnitude) reported in published reports. Image-based meta
      analysis (IBMA) methods use the full statistic images, and allow the use of
      hierarchical mixed effects models that account for differing intra-study variance
      and modeling of random inter-study variation. The purpose of this work is to
      compare image-based and coordinate-based meta-analysis methods applied to the
      same dataset, a group of 15 fMRI studies of pain, and to quantify the information
      lost by working only with the coordinates of peak activations instead of the full
      statistic images. We apply a 3-level IBMA mixed model for a "mega-analysis", and
      highlight important considerations in the specification of each model and
      contrast. We compare the IBMA result to three CBMA methods: ALE (activation
      likelihood estimation), KDA (kernel density analysis) and MKDA (multi-level
      kernel density analysis), for various CBMA smoothing parameters. For the datasets
      considered, we find that ALE at sigma=15 mm, KDA at rho=25-30 mm and MKDA at
      rho=15 mm give the greatest similarity to the IBMA result, and that ALE was the
      most similar for this particular dataset, though only with a Dice similarity
      coefficient of 0.45 (Dice measure ranges from 0 to 1). Based on this poor
      similarity, and the greater modeling flexibility afforded by hierarchical mixed
      models, we suggest that IBMA is preferred over CBMA. To make IBMA analyses
      practical, however, the neuroimaging field needs to develop an effective
      mechanism for sharing image data, including whole-brain images of both effect
      estimates and their standard errors.

PMID- 19166945
TI  - Adaptive filtering to reduce global interference in non-invasive NIRS measures of
      brain activation: how well and when does it work?
AB  - In previous work we introduced a novel method for reducing global interference,
      based on adaptive filtering, to improve the contrast to noise ratio (CNR) of
      evoked hemodynamic responses measured non-invasively with near infrared
      spectroscopy (NIRS). Here, we address the issue of how to generally apply the
      proposed adaptive filtering method. A total of 156 evoked visual response
      measurements, collected from 15 individuals, were analyzed. The similarity
      (correlation) between measurements with far and near source-detector separations
      collected during the rest period before visual stimulation was used as indicator
      of global interference dominance. A detailed analysis of CNR improvement in oxy
      hemoglobin (O(2)Hb) and deoxy-hemoglobin (HHb), as a function of the rest period
      correlation coefficient, is presented. Results show that for O(2)Hb measurements,
      66% exhibited substantial global interference. For this dataset, dominated by
      global interference, 71% of the measurements revealed CNR improvements after
      adaptive filtering, with a mean CNR improvement of 60%. No CNR improvement was
      observed for HHb. This study corroborates our previous finding that adaptive
      filtering provides an effective method to increase CNR when there is strong
      global interference, and also provides a practical way for determining when and
      where to apply this technique.

PMID- 19166946
TI  - Multiple neural networks supporting a semantic task: an fMRI study using
      independent component analysis.
AB  - A visual task for semantic access involves a number of brain regions. However,
      previous studies either examined the role of each region separately using
      univariate approach, or analyzed a single brain network using covariance
      connectivity analysis. We hypothesize that these brain regions construct several
      functional networks underpinning a word semantic access task, these networks
      being engaged in different cognitive components with distinct temporal
      characters. In this paper, multivariate independent component analysis (ICA) was
      used to reveal these networks based on functional magnetic resonance imaging
      (fMRI) data acquired during a visual and an auditory word semantic judgment task.
      Our results demonstrated that there were three task-related independent
      components (ICs), corresponding to various cognitive components involved in the
      visual task. Furthermore, ICA separation on the auditory task showed consistency
      of the results with our hypothesis, regardless of the input modalities.

PMID- 19166947
TI  - Neural basis of interaction between target presence and display homogeneity in
      visual search: an fMRI study.
AB  - The functional magnetic resonance imaging (fMRI) technique was used to
      investigate the functional neuroanatomy of the attention mechanisms employed in
      visual search with homogeneous or heterogeneous displays. Participants were asked
      to search for a vertically oriented bar among distractor bars with the same or
      different orientations, with half of the trials being target-present and the
      other half being target-absent. Behaviorally, RTs were slower for target-absent
      than for -present trials when the distractors were heterogeneous, but were faster
      for target-absent than for -present trials when the distractors were homogeneous.
      At the neural level, a widely distributed brain network was involved in this
      interaction. The bilateral frontal eye field, intraparietal sulcus, precentral
      gyrus and supplementary eye field may play a role in representing the target
      against distractors and further in detecting and responding to the presence of
      the target. The right superior frontal gyrus and the bilateral temporal-parietal
      junction may play a role in filtering distracting information in the search
      process.

PMID- 19166948
TI  - Laser-evoked potential P2 single-trial amplitudes covary with the fMRI BOLD
      response in the medial pain system and interconnected subcortical structures.
AB  - Pain is a complex experience with sensory, emotional and cognitive aspects. The
      cortical representation of pain - the pain matrix - consists of a network of
      regions including the primary (S1) and secondary (S2) sensory cortex, insula, and
      anterior cingulate cortex (ACC). These structures interact with brain regions
      such as the prefrontal cortex and the amygdalae. Simultaneous EEG/fMRI
      (electroencephalography/functional magnetic resonance imaging) has recently been
      introduced as a method to study the spatiotemporal characteristics of cognitive
      processes with high spatial and high temporal resolution at the same time. The
      present study was conducted to clarify if single trial EEG-informed BOLD modeling
      supports the definition of functional compartments within the pain matrix and
      interconnected regions. Twenty healthy subjects received painful laser
      stimulation while EEG and the fMRI blood oxygen level dependent (BOLD) signal
      were recorded simultaneously. While the laser-evoked N2 potential provided no
      additional information for BOLD modeling, the regressor obtained from the single
      trial laser-evoked P2 potential explained additional variance in a network of
      cortical and subcortical structures that largely overlapped with the pain matrix.
      This modeling strategy yielded pronounced activation in the ACC, right amygdala
      and thalamus. Our results suggest that laser-evoked potential (LEP) informed fMRI
      can be used to visualize BOLD activation in the pain matrix with an emphasis on
      functional compartments (as defined by the temporal dynamics of the LEP) such as
      the medial pain system. Furthermore, our findings suggest a concerted effort of
      the ACC and the amygdala in the cognitive-emotional evaluation of pain.

PMID- 19166949
TI  - Genetic diversification and demographic history of the cactophilic pseudoscorpion
      Dinocheirus arizonensis from the Sonoran Desert.
AB  - Sequence data from a segment of the mitochondrial cytochrome c oxidase subunit I
      (COI) gene were used to examine phylogenetic relationships, estimate gene flow
      and infer demographic history of the cactophilic chernetid pseudoscorpion,
      Dinocheirus arizonensis (Banks), from the Sonoran Desert. Phylogenetic trees
      resolved two clades of D. arizonensis, one from mainland Sonora, Mexico and
      southern Arizona (clade I) and the other from the Baja California peninsula and
      southern Arizona (clade II). The two clades were separated by a mean genetic
      distance (d) of approximately 2.6%. Hierarchical analysis of molecular variance
      indicated highly significant population structuring in D. arizonensis (overall
      Phi(ST)=0.860; P<0.0001), with 80% of the genetic variation distributed among the
      two clades. Most pairwise comparisons of Phi(ST) among populations within each
      clade, however, were not significant. The results suggest that phoretic dispersal
      on vagile cactophilic insects such as the neriid cactus fly Odontoloxozus
      longicornis (Coquillett) provides sufficient gene flow to offset the accumulation
      of unique haplotypes within each clade of the non-vagile pseudoscorpion.
      Preliminary results on dispersal capability of O. longicornis were consistent
      with this conclusion. Tests designed to reconstruct demographic history from
      sequence data indicated that both clades of D. arizonensis, as well as O.
      longicornis, have experienced historical population expansions. Potential
      barriers to gene flow that may have led to genetic isolation and diversification
      in clades I and II of D. arizonensis are discussed.

PMID- 19166950
TI  - Evolution of reduced and compact chloroplast genomes (cpDNAs) in gnetophytes:
      selection toward a lower-cost strategy.
AB  - The cpDNA of Welwitschia mirabilis (the only species of Welwitschiales) was
      recently reported to be the most reduced and compact among photosynthetic land
      plants. However, cpDNAs of the other two gnetophyte lineages (viz. Ephedrales and
      Gnetales) have not yet been studied. It remains unclear what underlining
      mechanisms have downsized the cpDNA. To pin down major factors for cpDNA
      reduction and compaction in gnetophytes, we have determined 4 complete cpDNAs,
      including one from each of the 3 gnetophyte orders, Ephedra equisetina, Gnetum
      parvifolium, and W. mirabilis, and one from the non-Pinus Pinaceae, Keteleeria
      davidiana. We report that the cpDNAs of E. equisetina (109,518bp) and
      G.parvifolium (114,914bp) are not only smaller but more compact than that of W.
      mirabilis (118,919bp). The gnetophyte cpDNAs have commonly lost at least 18 genes
      that are retained in other seed plants. Furthermore, they have significantly
      biased usages of AT-rich codons and shorter introns and intergenic spaces, which
      are largely due to more deletions at inter-operon than intra-operon spaces and
      removal of segment sequences rather than single-nucleotides. We show that the
      reduced gnetophyte cpDNAs clearly resulted from selection for economy by
      deletions of genes and non-coding sequences, which then led to the compactness
      and the accelerated substitution rates. The smallest C-values in gnetophyte
      nuclear DNAs and the competitive or resource-poor situations encountered by
      gnetophytes further suggest a critical need for an economic strategy.

PMID- 19166951
TI  - Multiple evolution of sexual dichromatism in African reed frogs.

PMID- 19166952
TI  - Molecular insights into the phylogeny and subgeneric classification of Frullania
      Raddi (Frullaniaceae, Porellales).
AB  - With an estimated 300-375 species, Frullania is the largest genus of Porellales
      and forms a major clade of leafy liverworts. The cosmopolitan genus includes
      mostly epiphytes and represents an important component of the cryptogamic
      vegetation in various, especially tropical, habitats. There have been abundant
      changes and modifications to the infrageneric classification of Frullania, with
      up to fifteen subgenera and numerous sections solely based on morphology. Here we
      present the first molecular phylogeny of Frullania using four markers (rbcL,
      psbA, trnL-trnF region of cp DNA, nr5.8S-ITS-2 region) and 171 accessions from
      throughout the range. The molecular data provide evidence for the monophyly of
      several subgenera and support intercontinental ranges of these clades. Previous
      subgeneric assignment for a suite of taxa based on morphological evidence is not
      supported by the molecular data. Representatives of the genera Amphijubula,
      Neohattoria and Schusterella are nested in robust subclades of Frullania. Basal
      relationships within Frullania are largely unsupported. Based on the outcome of
      the phylogenetic analyses we present a revised supraspecific classification and
      provide evidence for the monophyly of some morphological species. Disjunct
      distributional patterns within Frullania cannot be explained by Gondwanan
      vicariance.

PMID- 19166953
TI  - Tracking the evolutionary history of polyploidy in Fragaria L. (strawberry): new
      insights from phylogenetic analyses of low-copy nuclear genes.
AB  - Phylogenetic utility of two nuclear genes (GBSSI-2 and DHAR) was explored in
      genus Fragaria in order to clarify phylogenetic relationships among taxa and to
      elucidate the origin of the polyploid species. Orthology of the amplified
      products was assessed by several methods. Our results strongly suggest the loss
      of one GBSSI duplicated copy (GBSSI-1) in the Fragariinae subtribe. Phylogenetic
      analyses provided new insights into the evolutionary history of Fragaria, such as
      evidence supporting the presence of three main diploid genomic pools in the genus
      and demonstrating the occurrence of independent events of polyploidisation. In
      addition, the data provide evidence supporting an allopolyploid origin of the
      hexaploid F. moschata, and the octoploids F. chiloensis, F. iturupensis and F.
      virginiana. Accordingly, a new pattern summarizing our present knowledge on the
      Fragaria evolutionary history is proposed. Additionally, sequence analyses also
      revealed relaxed constraints on homoeologous copies at high ploidy level, as
      demonstrated by deletion events within DHAR coding sequences of some allo
      octoploid haplotypes.

PMID- 19166954
TI  - Epiblast isolation by a new four stage method (peeling) from whole bovine cloned
      blastocysts.
AB  - We have established a new 4 stage epiblast isolation method from whole bovine
      cloned blastocysts without using immunosurgery. The new "peeling" method consists
      of dissolution of the zona pellucida (first stage), elimination of mural
      trophoblast (second stage), isolation of primitive endoderm and epiblast from
      polar trophoblast (third stage), and isolation of epiblast from primitive
      endoderm (fourth stage). The bovine cloned blastocyst consists of 4 different
      types of cells showing abundant alkaline phosphatase activity. The epiblast
      origin of isolated cells was confirmed by in vitro differentiation of isolated
      cells to tubulin beta3-positive neurons and by embryoid body formation. The
      bovine cloned blastocyst origin of isolated epiblasts was confirmed by
      microsatellite analysis and mitochondrial DNA sequencing analysis. This new
      method might accelerate establishment of somatic cell nuclear transfer derived
      embryonic stem cell lines from bovine and other mammals.

PMID- 19166955
TI  - Identification and characterization of a novel gene, TrCCD1, and its possible
      function in hyphal growth and conidiospore development of Trichoderma reesei.
AB  - To investigate genes with essential functions during hyphal growth or sporulation
      in the asexual filamentous fungus Trichoderma reesei, we screened a collection of
      T-DNA insertion mutants and identified the genomic integration events. Two
      mutants with abnormal phenotypes, named as ccdO and ccdP, were found to have
      independent T-DNA insertions into a putative TrCCD1 gene locus, the product of
      which has significant homology to carotenoid cleavage dioxygenases (CCDs).
      Compared to the parental strain, both mutants tended to produce slow-growing
      hyphae and had a more than 50% reduction in colony growth rate. Simultaneously,
      the hyphae of the growing mutants formed wilting tip while the parental strain
      elongated straightly. To the effect of the TrCCD1 mutation on the conidiospore
      development, less spores were formed in the mutants than in the parental strain.
      In addition, disruption of TrCCD1 resulted in another phenotype characterized by
      a remarkable enhancement in the total carotenoid content. When the wild-type
      TrCCD1 gene was reintroduced into the ccd mutants, the abnormal phenotypes were
      rescued. These results suggest that TrCCD1 is involved in carotenoid metabolism
      and likely required for hyphal growth and conidiospore development in filamentous
      fungi T. reesei.

PMID- 19166956
TI  - Platinum nanoparticle antioxidants inhibit pulmonary inflammation in mice exposed
      to cigarette smoke.
AB  - Recent evidence implicates increased oxidative stress as an important mechanism
      of the pulmonary inflammation that occurs in cigarette smokers. Since cigarette
      smoke (CS) contains and generates a large amount of reactive oxygen species (ROS)
      that elicit pulmonary inflammation, antioxidants may become effective therapeutic
      agents for CS-related inflammatory lung diseases, such as chronic obstructive
      pulmonary disease. Platinum nanoparticles stabilized with polyacrylate to form a
      stable colloid solution (PAA-Pt) are a new class of antioxidants that has been
      shown to efficiently quench ROS. In the present study we investigated the
      therapeutic effects of PAA-Pt on pulmonary inflammation in smoking mice. PAA-Pt
      or saline was administered intranasally to DBA/2 mice, which were then exposed to
      CS or control air daily for 3 days. Mice were sacrificed 4h after their final
      exposure to CS or control air. CS exposure caused depletion of antioxidant
      capacity, NFkappaB activation, and neutrophilic inflammation in the lungs of
      mice, and intranasal administration of PAA-Pt prior to CS exposure was found to
      inhibit these changes. Intranasal administration of PAA-Pt alone did not elicit
      pulmonary inflammation or toxicity. In in vitro experiments, treatment of
      alveolar-type-II-like A549 cells with PAA-Pt inhibited cell death after exposure
      to a CS extract. These results suggest that platinum nanoparticles act as
      antioxidants that inhibit pulmonary inflammation induced by acute cigarette
      smoking.

PMID- 19166957
TI  - Effect of mode of administration on guaifenesin pharmacokinetics and expectorant
      action in the rat model.
AB  - AIM: Guaifenesin is a very commonly used and prescribed oral expectorant drug.
      However, its mechanism of action is not completely elucidated and the available
      information is limited. The purpose was to evaluate whether guaifenesin action on
      respiratory tract secretion is mediated through a reflex stimulation of the
      gastric mucosa or by the systemic exposure due to the absorption of the drug to
      the blood circulation. METHODS: Guaifenesin was administered to rats by various
      routes: intravenous bolus, oral gavage, and gastric, jejunal or cecal infusions
      (through surgically implanted catheters). Phenol red respiratory tract secretion
      (after intraperitoneal or intravenous injection) was used as a marker for degree
      of expectorant action. Administration of saline by gavage was used as control.
      RESULTS: Respiratory secretion following oral bolus was approximately 2-fold
      higher (p<0.05) than that of control. Following IV administration the increase of
      respiratory secretion did not occur despite the fact that systemic exposure to
      guaifenesin was 1.5-fold higher than following oral administration. The abdominal
      surgery was found to eliminate the effect of guaifenesin although it did not
      change systemic absorption. Guaifenesin was equally absorbed from all parts of
      the gastrointestinal tract. CONCLUSIONS: It was demonstrated that expectorant
      action of guaifenesin is mediated by stimulation of the gastrointestinal tract
      and not by the systemic exposure to the drug.

PMID- 19166958
TI  - A vegetable oil feeding history affects digestibility and intestinal fatty acid
      uptake in juvenile rainbow trout Oncorhynchus mykiss.
AB  - Future expansion of aquaculture relies on the use of alternatives to fish oil in
      fish feed. This study examined to what extent the nature of the feed oil affects
      intestinal lipid uptake properties in rainbow trout. The fish were fed a diet
      containing fish (FO), rapeseed (RO) or linseed (LO) oil for 8 weeks after which
      absorptive properties were assessed. Differences in digestibility due to feed oil
      history were measured using diet FO with an indigestible marker. Intestinal
      integrity, paracellular permeability, in vitro transepithelial fatty acid
      transport (3H-18:3n-3 and 14C-16:0) and their incorporation into intestinal
      epithelia were compared using Ussing chambers. Feed oil history did not affect
      the triacylglycerol/phosphatidylcholine ratio (TAG/PC) of the newly synthesized
      lipids in the segments. The lower TAG/PC ratio with 16:0 (2:1) than with 18:3
      (10:1) showed the preferential incorporation of 16:0 into polar lipids. The FO
      feeding history decreased permeability and increased transepithelial resistance
      of the intestinal segments. Transepithelial passage rates of 18:3n-3 were higher
      when pre-fed LO compared to RO or FO. Similarly, pre-feeding LO increased
      apparent lipid and fatty acid digestibilities compared to RO or FO. These results
      demonstrate that the absorptive intestinal functions in fish can be altered by
      the feed oil history and that the effect remains after a return to a standard
      fish oil diet.

PMID- 19166959
TI  - Sex differences in digestive traits in sexually size-dimorphic birds: Insights
      from an assimilation efficiency experiment on black-tailed godwit.
AB  - Digestive assimilation efficiency is considered a trait with important
      implications for animal ecology. However, practically all studies have ignored
      the importance of sex differences in food assimilation efficiency (AE). Here, we
      investigated sex differences in dietary and physiological parameters in the Black
      tailed Godwit Limosa limosa limosa feeding on rice seeds, a species with sexual
      dimorphism in body size and body mass. Gross daily food intake, gross energy
      intake, gross energy output and metabolizable energy intake did not vary
      significantly between sexes, but godwit females showed lower faeces energy
      density and higher AE than males. Mass-specific AE was similar in males and
      females, and the difference in AE could be attributed to the females' greater
      body mass. We suggest that a differential AE could play a role in explaining sex
      differences in habitat or micro-habitat selection during the non-breeding season
      in bird species with sexual dimorphism in size. Finally, we addressed the
      question about assimilation efficiency accuracy in models that estimate prey
      acquisitions by declining shorebirds as the Black-tailed Godwit.

PMID- 19166960
TI  - The effects of 2-bromopalmitate on the fatty acid composition in differentiating
      adipocytes of red sea bream (Pagrus major).
AB  - To determine whether external factors affect the adipogenic function of fish
      adipocytes, the effects of 2-bromopalmitate (a PPAR agonist) on the fatty acid
      composition in differentiating adipocytes of red sea bream were investigated in
      vitro. In the presence of 2-bromopalmitate, the red sea bream adipocytes were
      differentiated and the effects on the fatty acid composition and the adipogenic
      gene expression were analyzed. With the level of 2-bromopalmitate, the content of
      16:1n-7, a delta-9 desaturation product, increased in association with the
      increase in a stearoyl CoA desaturase (SCD) gene expression level while the
      triglyceride accumulation was not affected. Subsequently, the effects on the
      bioconversion of the n-3 and n-6 fatty acids, which are main series of dietary
      essential fatty acids, were examined. In the presence of 300 microM of 18:3n-3 or
      18:2n-6, red sea bream stromal-vascular cells accumulated the lipid in the
      cytoplasm within 3 days by the fatty acid uptake with the increase of
      corresponding fatty acid contents. Furthermore, in both the 18:3n-3 and 18:2n-6
      stored cells, the products of delta-6 desaturation (18:4n-3 and 18:3n-6,
      respectively) and C(18-20) elongation (20:3n-3 and 20:2n-6, respectively) were
      detected. However, neither the delta-6 desatutration nor C(18-20) elongation of
      18:3n-3 and 18:2n-6 were enhanced by 2-bromopalmitate treatment. In conclusion,
      the results indicate that the adipocyte function in fish, e.g. adipogenic gene
      expression and fatty acid composition, can be modified by external factors and a
      main effect of 2-bromopalmitate is the increase in the content of delta-9
      desaturation product by stimulating the SCD gene expression.

PMID- 19166961
TI  - Molecular cloning, mRNA expression, and characterization of HSP90 gene from
      Chinese mitten crab Eriocheir japonica sinensis.
AB  - HSP90 is a highly conserved molecular chaperone important in the maturation of a
      broad spectrum of proteins. Using expressed sequence tag (EST) and rapid
      amplification of cDNA ends (RACE) techniques, an HSP90 gene designated as
      EjsHSP90 was cloned and characterized from the Chinese mitten crab Eriocheir
      japonica sinensis. The full-length cDNA of EjsHSP90 is 2,517 bp and contains an
      open reading frame of 2157 bp which encodes a 718 amino acid polypeptide (82.8
      kDa) bearing characteristics of the HSP90 family and an ATP binding domain.
      Sequence alignment shows that EjsHSP90 shared 79%-96% identity with HSP90
      sequences reported in other animals, and it shares identical structural features.
      Fluorescent real-time quantitative RT-PCR approach was performed to examine the
      expression profiles of EjsHSP90 mRNA by testing its relative level in three types
      of tissues at three different developmental stages, respectively. We found that
      EjsHSP90 is expressed throughout the three developmental stages but expression
      levels varied among different body parts of crabs. EjsHSP90 mRNA expression in
      the abdomen of the first crab stage is consistently higher than that of the other
      two stages, suggesting that EjsHSP90 gene is involved in the crabs' early
      developmental process, especially in the crab brachyurization process. Results
      from quantitative RT-PCR excluded the possibility that the expression of EjsHSP90
      mRNA is induced primarily by osmotic stress. Phylogenetic analyses reveal that
      HSP90 gene is informative and complementary for reconstruction of arthropod
      phylogenetic relationships.

PMID- 19166962
TI  - Protein kinase C-Fyn kinase cascade mediates the oleic acid-induced disassembly
      of neonatal rat cardiomyocyte adherens junctions.
AB  - Oleic acid (OA) affects assembly of gap junctions in neonatal cardiomyocytes.
      Adherens junction (AJ) regulates the stability of gap junction integrity;
      however, the effect of OA on AJ remains largely unexplored. The distribution of N
      cadherin and catenins at cell-cell junction was decreased by OA. OA induced
      activation of protein kinase C(PKC)-alpha and -epsilon and Src family kinase, and
      all three kinases were involved in the oleic acid-induced disassembly of the
      adherens junction, since it was blocked by pretreatment with Go6976 (a PKCalpha
      inhibitor), epsilonV1-2 (a PKCepsilon inhibitor), or PP2 (a Src family kinase
      inhibitor). Src family kinase appeared to be the downstream of PKC-alpha and 
      epsilon, as blockade of either PKC-alpha or -epsilon activity prevented the OA
      induced activation of Src family kinase. Immunoprecipitation analyses showed that
      OA activated Fyn and Fer. OA promoted the association of p120 catenin/beta
      catenin with Fyn and Fer and caused increased tyrosine phosphorylation of p120
      catenin and beta-catenin, resulting in decreased binding of the former to N
      cadherin and of the latter to alpha-catenin. Pretreatment with PP2 abrogated this
      OA-induced tyrosine phosphorylation of p120 catenin and beta-catenin and restored
      the association of N-cadherin with p120 catenin and that of beta-catenin with
      alpha-catenin. In conclusion, these results show that OA activates the PKC-Fyn
      signaling pathway, leading to the disassembly of the AJ. Therefore, inhibitors of
      PKC-alpha/-epsilon and Src family kinase are potential candidates as
      cardioprotection agents against OA-induced heart injury during ischemia
      reperfusion.

PMID- 19166964
TI  - Phycocyanin protects INS-1E pancreatic beta cells against human islet amyloid
      polypeptide-induced apoptosis through attenuating oxidative stress and modulating
      JNK and p38 mitogen-activated protein kinase pathways.
AB  - It is widely accepted that human islet amyloid polypeptide (hIAPP) aggregation
      plays an important role in the loss of insulin-producing pancreatic beta cells.
      hIAPP-induced cytotoxicity is mediated by generation of reactive oxygen species
      (ROS). Phycocyanin (PC) is a natural compound from blue-green algae that is
      widely used as food supplement. Currently, little is known about the effects of
      PC on beta cells with the presence of hIAPP. The aim of this study was to
      investigate the in vitro protective effects of PC on INS-1E rat insulinoma beta
      cells against hIAPP-induced cell death, as well as the underlying mechanisms. Our
      results showed that hIAPP-induced cell death with apoptotic characteristics
      including growth inhibition, chromatin condensation and DNA fragmentation.
      However, cytotoxicity of hIAPP was significantly attenuated by co-incubation of
      the cells with PC. The results of Western blotting showed that activation of
      caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP) in hIAPP-treated
      cells was blocked by PC. Moreover, PC significantly prevented the hIAPP-induced
      overproduction of intracellular ROS and malondialdehyde (MDA), as well as changes
      in activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)
      enzymes. Furthermore, hIAPP triggered the activation of mitogen-activated protein
      kinases (MAPKs), and these effects were effectively suppressed by PC. Taken
      together, our results suggest that PC protects INS-1E pancreatic beta cells
      against hIAPP-induced apoptotic cell death through attenuating oxidative stress
      and modulating c-Jun N-terminal kinase (JNK) and p38 pathways.

PMID- 19166963
TI  - LPS-induced suppression of macrophage cholesterol efflux is mediated by adipocyte
      enhancer-binding protein 1.
AB  - Macrophages facilitate clearance of cholesterol from the body via reverse
      cholesterol transport (RCT). The first event in RCT is internalization of
      modified low density lipoprotein by macrophages, upon which PPARgamma1 and
      LXRalpha signaling pathways are turned on, leading to the transactivation of a
      cascade of genes (e.g. ABCA1 and ABCG1), whose products promote macrophage
      cholesterol efflux. Down-regulation of macrophage cholesterol efflux mediators
      leads to an imbalance in cholesterol homeostasis, promoting foam cell formation.
      Lipopolysaccharide (LPS) has been shown to suppress PPARgamma1 and its downstream
      target genes in macrophages, inducing foam cell formation; a key mechanism
      proposed to underlie bacterial infection-induced atherosclerosis. Herein, we show
      that adipocyte enhancer-binding protein 1 (AEBP1) is up-regulated during monocyte
      differentiation. Moreover, we provide experimental evidence suggesting that AEBP1
      expression is induced by LPS, and that LPS-induced down-regulation of pivotal
      macrophage cholesterol efflux mediators, leading to foam cell formation, is
      largely mediated by AEBP1. Although AEBP1-independent pathways seem to contribute
      to these LPS effects, such pathways can only mediate lesser and delayed effects
      of LPS on macrophage cholesterol efflux and development of foam cells. We
      speculate that AEBP1 may serve as a potential therapeutic target for the
      prevention/treatment of bacterial infection-induced atherosclerosis.

PMID- 19166965
TI  - Integrin cleavage facilitates cell surface-associated proteolysis required for
      vascular smooth muscle cell invasion.
AB  - Vascular smooth muscle cell (VSMC) invasion is a key element in atherogenesis and
      restenosis, requiring integrins for adhesion/de-adhesion as well as matrix
      metalloproteinases (MMPs) for focalized proteolysis. Among the MMP family, pro
      MMP-2 is unique in its activation, depending on the formation of a multiprotein
      complex with MT1-MMP/TIMP-2 at the cell surface, in which integrin alphavbeta3
      participates. Integrin alphav and MT1-MMP are synthesized from precursors via
      furin-dependent cleavage of their pro-peptide. Furin is the prototypical
      proprotein convertase highly expressed in VSMCs and human atherosclerotic
      lesions. Its precise role in the tight network involving MMPs/integrins and their
      coordination and cooperation required for VSMC invasion is unknown. We
      demonstrate that furin-inhibition with decanoyl-RVKR-chloromethylketone inhibits
      VSMC invasion in a comparable degree to MMP inhibitors, which reduce the MT1-MMP
      MMP-2 proteolytic cascade. Furin-inhibition did not prevent MT1-MMP/MMP-2
      maturation. In contrast, it strongly reduced pro-alphav cleavage, but did not
      lessen its cell membrane expression. However, inhibition of pro-alphav processing
      via furin-inhibition strongly reduced pro-MMP-2 binding to the cell surface,
      thereby lessening its full maturation and diminishing the cell surface in situ
      proteolysis required for invasion. Thus, our data demonstrate a novel mechanism
      of furin-dependent alphav cleavage that enhances pro-MMP-2 binding and activation
      at the cell membrane in cooperation with MT1-MMP in primary VSMCs. Processing of
      alphav by furin contributes to the recruitment of enzymatic energy to the cell
      surface, thereby providing focalized proteolysis associated with VSMC invasion.

PMID- 19166966
TI  - IL1B promoter polymorphism regulates the expression of gastric acid stimulating
      hormone gastrin.
AB  - It is important to dissect the effect of the alternative alleles of a functional
      SNP on the entire biochemical pathway for the complete understanding of the
      mechanism of the manifestation of complex diseases. IL1B-511C>T and -31C>T
      promoter polymorphisms have been suggested as potential susceptibility loci for
      Helicobacter pylori associated gastroduodenal diseases. We report that altered
      expression of IL1B due to a specific polymorphism in its promoter modulates the
      expression of gastrin, an acid regulating hormone. Treatment of gastric carcinoma
      cells, AGS, with IL1B resulted in a 20-fold reduction in gastrin expression.
      Gastrin promoter assay showed that IL1B inhibits gastrin expression at the
      transcriptional level and part of this inhibitory process is mediated via
      activation of NFkappaB and involvement of HDACs. An almost 3-fold increase in
      IL1B expression was observed when AGS cells were transfected with -31TIL1B
      expression plasmid in comparison to -31CIL1B. The -31TIL1B induced a 2-fold
      greater repression of the gastrin luciferase activity compared to -31CIL1B. This
      signaling of the -31TIL1B variant allele driven IL1B revealed an almost 1.5-fold
      greater expression of NFkappaB. Thus, this study showed that a single base
      substitution at the -31 position of the IL1B promoter brought about differential
      expression of IL1B which differentially altered both NFkappaB activation and
      gastrin expression.

PMID- 19166967
TI  - Stearoyl-CoA desaturase and its relation to high-carbohydrate diets and obesity.
AB  - Obesity is currently a worldwide epidemic and public health burden that increases
      the risk for developing insulin resistance and several chronic diseases such as
      diabetes, cardiovascular diseases and non-alcoholic fatty liver disease. The
      multifactorial causes of obesity include several genetic, dietary and lifestyle
      variables that together result in an imbalance between energy intake and energy
      expenditure. Dietary approaches to limit fat intake are commonly prescribed to
      achieve the hypocaloric conditions necessary for weight loss. But dietary fat
      restriction is often accompanied by increased carbohydrate intake, which can
      dramatically increase endogenous fatty acid synthesis depending upon carbohydrate
      composition. Since both dietary and endogenously synthesized fatty acids
      contribute to the whole-body fatty acid pool, obesity can therefore result from
      excessive fat or carbohydrate consumption. Stearoyl-Coenzyme A desaturase-1
      (SCD1) is a delta-9 fatty acid desaturase that converts saturated fatty acids
      into monounsaturated fatty acids (MUFA) and this activity is elevated by dietary
      carbohydrate. Mice lacking Scd1 are protected from obesity and insulin resistance
      and are characterized by decreased fatty acid synthesis and increased fatty acid
      oxidation. In this review, we address the association of high-carbohydrate diets
      with increased SCD activity and summarize the current literature on the subject
      of SCD1 and body weight regulation.

PMID- 19166968
TI  - Muscular anatomy of the legs of the forward walking crab, Libinia emarginata
      (Decapoda, Brachyura, Majoidea).
AB  - Decapod crustaceans have been the focus of neuroethological studies for decades.
      With few exceptions, however, their musculature remains scarcely described. We
      study the neuroethology of legged locomotion in the portly spider crab, Libinia
      emarginata (Brachyura, Majoidea), which preferentially walks forward. Majoid
      crabs are thought to be among the first to have adopted the crab form
      (carcinification) from lobster-like ancestors, making them interesting subjects
      for comparative and phylogenetic studies. The radial arrangement of the legs
      around the thorax, coupled with its unidirectional walking modality makes L.
      emarginata a good candidate for the presence of anterior and posterior limb
      specializations. Here we describe the complete muscular anatomy of all the
      pereopods of L. emarginata and compare our findings with other decapods described
      in the literature. The number of proximal muscle bundles differs between the
      anterior and posterior pereopods of L. emarginata. We describe an intersegmental
      bundle of the flexor muscle similar to the one present in distantly related,
      forward walking macruran species. The behavioral repertoire, amenability to
      experimental investigations, and phylogenetic position make spider crabs useful
      species for the study of the neural control of legged locomotion. To our
      knowledge, this is the first instance of a complete description and comparison of
      the musculature in all the locomotor appendages of one species.

PMID- 19166969
TI  - Distinctive features of the alimentary canal of a fungus-feeding hemipteran,
      Mezira granulata (Heteroptera: Aradidae).
AB  - Hemiptera (Insecta) have specialized mouthparts for fluid feeding as well as
      distinctive midgut epithelia. The gut epithelia of Mezira granulata, a member of
      an unusual family of Hemiptera - the Aradidae - are described in this manuscript.
      Species of this family are thought to feed on fungi instead of plant or animal
      materials, as is more typical of the Hemiptera. The midgut lumen is lined by
      perimicrovillar membranes rather than by the peritrophic membranes formed by
      specialized midgut cells of stomodeal valves found at foregut-midgut interfaces
      in many insects. However, a stomodeal valve also occurs at the foregut-midgut
      boundary in these aradid bugs, and certain midgut epithelial cells located at the
      interface are specialized for secretion of an electron-dense extracellular matrix
      that fills the midgut lumen in the vicinity of the stomodeal valve. In addition
      to the distinctive cellular architecture of the apical (luminal) surfaces of
      midgut epithelial cells, luminal surfaces of the aradid hindgut epithelia are
      regionally differentiated into three regions with very different cuticles.

PMID- 19166970
TI  - Neuropsychological profiles of patients with juvenile myoclonic epilepsy and
      their siblings: a preliminary controlled experimental video-EEG case series.
AB  - OBJECTIVE: The aim of this study was to examine expressive language, memory, and
      higher executive tasks in patients with juvenile myoclonic epilepsy (JME) as
      compared with their siblings and a normal control group under video-EEG
      conditions. METHODS: Eight sibling pairs, one in each pair with JME, were
      compared with 16 controls matched for age, sex, ethnicity, and educational level.
      The participants were administered a standard comprehensive set of
      neuropsychological measures to assess emotional well-being, intelligence, memory,
      language, visuospatial skills, reaction time, attention, and higher executive
      function, during and without video-EEG recording. RESULTS: The JME group differed
      significantly from controls on measures of phonemic and semantic verbal fluency.
      They also scored significantly higher on the Dysexecutive Questionnaire, being
      much more likely to report traits associated with executive dysfunction.
      Qualitative inspection of the data suggested a trend for patients with JME and
      their siblings to perform worse than controls on some measures, notably those of
      expressive language and higher executive function, but on other measures the
      differences were not statistically significant. In contrast, the JME and sibling
      group performed as well as controls on the Rey Complex Figure and other tests of
      visuospatial skills. CONCLUSION: The present controlled experimental case series
      provides support for a neuropsychological profile of patients with JME and their
      siblings. Significant impairments in verbal and executive functioning may have
      important ramifications for the social, occupational, and academic performance of
      people with JME. The apparent corresponding likeness in cognitive performance,
      exhibited independent of EEG activity, between patients with JME and their
      siblings warrants further exploration as similar cortical and subcortical
      structures may be implicated in these two groups.

PMID- 19166971
TI  - Race, ethnicity, and epilepsy research.

PMID- 19166972
TI  - From sardines to salmon: Influence of climate fluctuations on sudden unexpected
      death in epilepsy.

PMID- 19166973
TI  - A recent advance in the automatic indexing of the biomedical literature.
AB  - The volume of biomedical literature has experienced explosive growth in recent
      years. This is reflected in the corresponding increase in the size of MEDLINE,
      the largest bibliographic database of biomedical citations. Indexers at the US
      National Library of Medicine (NLM) need efficient tools to help them accommodate
      the ensuing workload. After reviewing issues in the automatic assignment of
      Medical Subject Headings (MeSH terms) to biomedical text, we focus more
      specifically on the new subheading attachment feature for NLM's Medical Text
      Indexer (MTI). Natural Language Processing, statistical, and machine learning
      methods of producing automatic MeSH main heading/subheading pair recommendations
      were assessed independently and combined. The best combination achieves 48%
      precision and 30% recall. After validation by NLM indexers, a suitable
      combination of the methods presented in this paper was integrated into MTI as a
      subheading attachment feature producing MeSH indexing recommendations compliant
      with current state-of-the-art indexing practice.

PMID- 19166974
TI  - A semi-automatic method for quantification and classification of erythrocytes
      infected with malaria parasites in microscopic images.
AB  - Visual quantification of parasitemia in thin blood films is a very tedious,
      subjective and time-consuming task. This study presents an original method for
      quantification and classification of erythrocytes in stained thin blood films
      infected with Plasmodium falciparum. The proposed approach is composed of three
      main phases: a preprocessing step, which corrects luminance differences. A
      segmentation step that uses the normalized RGB color space for classifying pixels
      either as erythrocyte or background followed by an Inclusion-Tree representation
      that structures the pixel information into objects, from which erythrocytes are
      found. Finally, a two step classification process identifies infected
      erythrocytes and differentiates the infection stage, using a trained bank of
      classifiers. Additionally, user intervention is allowed when the approach cannot
      make a proper decision. Four hundred fifty malaria images were used for training
      and evaluating the method. Automatic identification of infected erythrocytes
      showed a specificity of 99.7% and a sensitivity of 94%. The infection stage was
      determined with an average sensitivity of 78.8% and average specificity of 91.2%.

PMID- 19166975
TI  - Towards identifying intervention arms in randomized controlled trials: extracting
      coordinating constructions.
AB  - BACKGROUND: Large numbers of reports of randomized controlled trials (RCTs) are
      published each year, and it is becoming increasingly difficult for clinicians
      practicing evidence-based medicine to find answers to clinical questions. The
      automatic machine extraction of RCT experimental details, including design
      methodology and outcomes, could help clinicians and reviewers locate relevant
      studies more rapidly and easily. AIM: This paper investigates how the comparison
      of interventions is documented in the abstracts of published RCTs. The ultimate
      goal is to use automated text mining to locate each intervention arm of a trial.
      This preliminary work aims to identify coordinating constructions, which are
      prevalent in the expression of intervention comparisons. METHODS AND RESULTS: An
      analysis of the types of constructs that describe the allocation of intervention
      arms is conducted, revealing that the compared interventions are predominantly
      embedded in coordinating constructions. A method is developed for identifying the
      descriptions of the assignment of treatment arms in clinical trials, using a full
      sentence parser to locate coordinating constructions and a statistical classifier
      for labeling positive examples. Predicate-argument structures are used along with
      other linguistic features with a maximum entropy classifier. An F-score of 0.78
      is obtained for labeling relevant coordinating constructions in an independent
      test set. CONCLUSIONS: The intervention arms of a randomized controlled trials
      can be identified by machine extraction incorporating syntactic features derived
      from full sentence parsing.

PMID- 19166976
TI  - Free peritoneal gas accumulation caused by pneumatosis coli after diagnostic
      gastrointestinal endoscopy.

PMID- 19166977
TI  - Linear immunoglobulin a bullous dermatitis, sclerosing cholangitis, and
      sacroilitis in a young man with ulcerative colitis.

PMID- 19166978
TI  - Skin lesions in a patient on therapy for chronic hepatitis C.

PMID- 19166979
TI  - Do predictors of mortality in upper gastrointestinal bleeding include a weekend
      time of admission?

PMID- 19166980
TI  - Safety of infliximab in inflammatory bowel disease needs to be debated.

PMID- 19166981
TI  - Differential expression of zebrafish gpia and gpib during development.
AB  - Glucose 6-phosphate isomerase (GPI), alternatively named phosphoglucose isomerase
      (PGI), autocrine motility factor (AMF) or neuroleukin (NLK), is a sugar metabolic
      enzyme catalyzing the interconversion between glucose-6-phosphate and fructose-6
      phosphate. When secreted out of the cell, it can induce cellular activities of
      neighboring cells. As a prerequisite to study the function of gpi during
      development, we analyzed the sequences and expression patterns of zebrafish gpia
      and gpib. Phylogenetic analyses indicate that gpia and gpib are two paralogs
      resulting from the teleost fish-specific whole genome duplication. In adult
      zebrafish, gpia is widely expressed in many tissues, whereas gpib is only
      expressed in heart, muscle, and at lower abundance in eye. During embryonic
      development, gpia mRNA is maternally deposited in cleavage and blastula embryos,
      but gpib mRNA is not. Zygotic expression of gpia mRNA initiates in the primitive
      gut of segmentation embryos, and its expression increases in eye, cerebellum,
      hindbrain, heart, pharyngeal arches, pectoral fin buds and gut of hatching
      embryos at 60hpf (hours post fertilization). At 72hpf, gpia mRNA is strongly
      expressed in the retina of eye, tectum, hindbrain, and gut derivatives such as
      liver, intestine and circular smooth muscle layer of the swim bladder. By
      contrast, gpib is expressed in the yolk syncytial nuclei of late blastula,
      gastrula and segmentation embryos. Somitic gpib expression initiates in late
      pharyngula embryos, and it is most prominent in the muscle of hatching embryos
      around 48-60hpf. Transcript of gpib is also expressed in the pectoral fins and
      portions of the pharyngeal arches in the hatching period. The differential
      expression of gpia and gpib in zebrafish suggests partition or divergence of gpi
      functions between the two duplicates.

PMID- 19166982
TI  - Identification of differentially expressed genes in the zebrafish hypothalamic
      pituitary axis.
AB  - The vertebrate hypothalamic-pituitary axis (HP) is the main link between the
      central nervous system and endocrine system. Although several signal pathways and
      regulatory genes have been implicated in adenohypophysis ontogenesis, little is
      known about hypothalamic-neurohypophysial development or when the HP matures and
      becomes functional. To identify markers of the HP, we constructed subtractive
      cDNA libraries between adult zebrafish hypothalamus and pituitary. We identified
      previously published genes, ESTs and novel zebrafish genes, some of which were
      predicted by genomic database analysis. We also analyzed expression patterns of
      these genes and found that several are expressed in the embryonic and larval
      hypothalamus, neurohypophysis, and/or adenohypophysis. Expression at these stages
      makes these genes useful markers to study HP maturation and function.

PMID- 19166983
TI  - Hydroxyethyl starch 130/0.4 prevents the early pulmonary inflammatory response
      and oxidative stress after hemorrhagic shock and resuscitation in rats.
AB  - BACKGROUND: This study was designed to determine the effects of various
      resuscitation fluids on pulmonary capillary leakage and pulmonary edema after HS
      and fluid resuscitation (HS/R) and to determine whether an antiinflammatory or
      antioxidative mechanism was involved. METHODS: We induced HS by bleeding male
      Sprague-Dawley rats to a blood pressure of 30 to 40 mm Hg for 60 min. 60 min
      later, the rats were killed (HS group) or immediately resuscitated with L-isomer
      lactated Ringer's solution (HS+LR group), shed blood (HS+BL group), or
      hydroxyethyl starch (HS+HES group) to maintain the blood pressure to the original
      value during the 60-min resuscitation period. 3 h after resuscitation, pulmonary
      capillary leakage and wet/dry weight ratio, levels of tumor necrosis factor (TNF)
      alpha, interleukin (IL)-6, malondialdehyde (MDA), oxidized and reduced
      glutathione (GSH and GSSG), myeloperoxidase (MPO) activity, nuclear factor (NF)
      kappaB, activator protein (AP)-1 activation, and lung microscopic and
      ultrastructural histological changes were measured. RESULTS: HES and BL treatment
      significantly improved pulmonary capillary leakage, wet/dry weight ratio and lung
      injuries after HS/R. In addition, both HES and BL could attenuate the increase in
      TNF-alpha, IL-6, MPO levels and NF-kappaB activation. However, HES but not BL
      could attenuate the increase in MDA level and GSSH/GSH ratio and AP-1 activation.
      CONCLUSIONS: HES might attenuate pulmonary injuries by modulating pulmonary
      inflammatory response and oxidative stress, whereas BL attenuates pulmonary
      injuries by modulating pulmonary inflammatory response but not oxidative stress.

PMID- 19166984
TI  - Drug transport mechanism of the AcrB efflux pump.
AB  - In Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa,
      tripartite multidrug efflux systems extrude cytotoxic substances from the cell
      directly into the medium bypassing periplasm and the outer membrane. In E. coli,
      the tripartite efflux system AcrA/AcrB/TolC is the pump that extrudes multiple
      antibiotics, dyes, bile salts and detergents. The inner membrane component AcrB,
      a member of the Resistance Nodulation cell Division (RND) family, is the major
      site for substrate recognition and energy transduction of the entire tripartite
      system. The drug/proton antiport processes in this secondary transporter are
      suggested to be spatially separated, a feature frequently observed for primary
      transporters like membrane-bound ATPases. The recently elucidated asymmetric
      structure of the AcrB trimer reveals three different monomer conformations
      proposed to represent consecutive states in a directional transport cycle. Each
      monomer shows a distinct tunnel system with entrances located at the boundary of
      the outer leaflet of the inner membrane and the periplasm through the periplasmic
      porter (pore) domain towards the funnel of the trimer and TolC. In one monomer a
      hydrophobic pocket is present which has been shown to bind the AcrB substrates
      minocyclin and doxorubicin. The energy conversion from the proton motive force
      into drug efflux includes proton binding in (and release from) the transmembrane
      part. The conformational changes observed within a triad of essential, titratable
      residues (D407/D408/K940) residing in the hydrophobic transmembrane domain appear
      to be transduced by transmembrane helix 8 and associated with the conformational
      changes seen in the periplasmic domain. From the asymmetric structure a possible
      peristaltic pump transport mechanism based on a functional rotation of the AcrB
      trimer has been postulated. The novel drug transport model combines the alternate
      access pump mechanism with the rotating site catalysis of F(1)F(o) ATPase as
      originally postulated by Jardetzky and Boyer, respectively, and suggests a
      working hypothesis for the transport mechanism of RND transporters in general.

PMID- 19166986
TI  - Blue native DIGE as a tool for comparative analyses of protein complexes.
AB  - Differential gel electrophoresis (DIGE) is based on pre-labeling of different
      protein fractions and their subsequent co-electrophoresis in a single gel.
      Cyanine based "CyDye DIGE Fluor minimal dyes" are used for the labeling reaction
      and 2D IEF/SDS PAGE is the preferential electrophoresis system for protein
      separation. The DIGE technology allows elimination of inconsistencies based on
      gel to gel variations and furthermore allows exact quantification of proteins
      separated by gel electrophoresis. Here we report applications of the DIGE
      technology in combination with another 2D gel system, Blue native/SDS PAGE. "Blue
      native DIGE" offers (i) systematic and quantitative comparison of protein
      complexes of related protein fractions, (ii) structural investigation of protein
      complexes, (iii) assignment of protein complexes to subcellular fractions like
      organelles and (iv) electrophoretic mapping of isoforms of subunits of protein
      complexes with respect to a larger proteome. The potential of "Blue native DIGE"
      is illustrated by analysis of organellar fractions from the plant Arabidopsis
      thaliana and the alga Polytomella. Use of the DIGE technology for topological
      investigations is discussed.

PMID- 19166985
TI  - Structural and mechanistic analyses of yeast mitochondrial thioredoxin Trx3
      reveal putative function of its additional cysteine residues.
AB  - The yeast Saccharomyces cerevisiae Trx3 is a key member of the thioredoxin system
      to control the cellular redox homeostasis in mitochondria. We solved the crystal
      structures of yeast Trx3 in oxidized and reduced forms at 1.80 and 2.10 A,
      respectively. Besides the active site, the additional cysteine residue Cys69 also
      undergoes a significant redox-correlated conformational change. Comparative
      structural analyses in combination with activity assays revealed that residue
      Cys69 could be S-nitrosylated in vitro. S-nitrosylation of Cys69 will decrease
      the activity of Trx3 by 20%, which is comparable to the effect of the Cys69Ser
      mutation. Taken together, these findings provided us some new insights into the
      putative function of the additional cysteine residues of Trx3.

PMID- 19166987
TI  - A local bone anabolic effect of rhFGF2-impregnated gelatin hydrogel by promoting
      cell proliferation and coordinating osteoblastic differentiation.
AB  - The bone anabolic effect of rhFGF2 is attributed to activation of proliferation
      and differentiation of osteoblasts. Concomitant up-regulation of Runx2 and Bmp2
      implies a coordinative function of FGF/FGFR signaling on osteoblast
      differentiation. INTRODUCTION: Duration and tissue concentration of growth factor
      exposure are important in tissue regeneration. This study analyzed the
      availability of rhFGF2 using a sustained release gelatin hydrogel system. To
      examine biological aspects of the bone anabolic effect, we carried out
      morphological and cell proliferation assays together with gene expression
      analyses of osteoblast related genes induced by rhFGF2 using localizing and
      quantifying procedures in vivo. MATERIALS AND METHODS: Bone formation induced by
      implantation of gelatin hydrogel impregnated with 20 microg rhFGF2 (rhFGF2(+))
      onto mice maxillae was analyzed by micro computed tomography, proliferating cell
      nuclear antigen (PCNA) immunohistochemistry, in situ hybridization and
      quantitative real time polymerase chain reaction combined with laser
      microdissection (LMD-QPCR). RESULTS: The bony maxilla was augmented to 1.58 times
      its original volume (p=0.002) by the implantation of rhFGF2(+) gelatin hydrogel.
      An increased number of PCNA-positive nuclei were observed among differentiated
      osteoblasts as well as undifferentiated mesenchymal cells. Fgfr1, Fgfr2 and Runx2
      were shown to be co-expressed mainly in differentiated osteoblasts but also in
      osteoblast marker-negative spindle-shaped cells that were scattered within the
      outer layer of hyperplastic periosteum. LMD-QPCR revealed up-regulation of Bmp2
      expression accompanied by increased transcription of Fgfr1, Fgfr2 and Runx2 by
      rhFGF2 controlled release. CONCLUSIONS: rhFGF2 sustained release results in bone
      formation on the maxilla by positively regulating the expansion and
      differentiation of osteoblastic cells. It is suggested that FGF/FGFR signaling
      coordinates a bone anabolic effect by simultaneously activating RUNX2 and BMP2
      pathways. The gelatin hydrogel system, which enables a sustained slow rate of
      release of rhFGF2 in tissue has advantages of optimizing bone regeneration.

PMID- 19166988
TI  - Coordination of complex bimanual multijoint movements under increasing cycling
      frequencies: the prevalence of mirror-image and translational symmetry.
AB  - The present study examined the principles underlying inter and intralimb
      coordination constraints during performance of bimanual elbow-wrist movements at
      different cycling frequencies (from 0.75 Hz to 2.50 Hz). Participants performed
      eight coordination tasks that consisted of a combination of in-phase (IN) and/or
      anti-phase (AN) coordination modes between both elbows and wrists (interlimb),
      with isodirectional (Iso) or non-isodirectional (NonI) coordination modes within
      each limb (intralimb). As expected, the principle of muscle homology (in-phase
      coordination), giving rise to mirror symmetrical movements with respect to the
      mid-sagittal plane, had a powerful influence on the quality of global
      coordinative behavior both between and within limbs. When this principle was
      violated (i.e., when the anti-phase mode was introduced in one or both joint
      pairs), the non-isodirectional intralimb mode exhibited a (de)stabilizing role in
      coordination, which became more pronounced at higher cycling frequencies.
      However, pattern loss with increasing cycling frequency resulted not only in
      convergence toward the more stable in-phase patterns with the elbows and wrists
      but also to the anti-phase patterns (which were associated with directional
      compatibility of within-limb motions). Moreover, participants generally preserved
      their initial mode of coordination (either in-phase or anti-phase) in the
      proximal joints (i.e., elbows) while shifting from anti-phase to in-phase (or
      vice versa) with their distal joint pair (i.e., wrists). Taken together, these
      findings reflect the impact of two immanent types of symmetry in bimanual
      coordination: mirror-image and translational symmetry.

PMID- 19166989
TI  - Non-differential return of fear in humans after a reinstatement procedure.
AB  - The present experiment investigated reinstatement of fear in humans using a
      differential fear conditioning preparation. In this experiment, one neutral
      stimulus (conditioned stimulus; CS+) was paired with an aversive stimulus
      (unconditioned stimulus; US) during the acquisition phase, while another neutral
      stimulus was not (CS-). This procedure led to a difference in responding between
      the CS+ and the CS- (i.e., differential conditioning). After this acquisition
      phase, an extinction phase followed, during which both CSs were presented without
      the US, resulting in a decrease in differential conditioned responding.
      Reinstatement refers to the return of extinguished conditioned responses due to
      the experience of US-only trials after the extinction phase. This phenomenon was
      investigated by presenting half of the participants (reinstatement group) with
      unpredictable USs after the extinction phase. The control group did not receive
      these USs after the extinction procedure. The results show that return of fear
      was clearly apparent after the reinstating USs. This return of fear was, however,
      not limited to the CS+. An increase in 'conditioned' responding was also observed
      for the control stimulus. This interesting observation will be discussed against
      the background of a number of recent theoretical conceptualizations of
      reinstatement.

PMID- 19166991
TI  - [A case of intrahepatic gastrinoma].
AB  - The Zollinger-Ellison syndrome is due to an endocrine gastrin-secreting tumor,
      the gastrinoma. This tumor is often malignant and patients develop metastases in
      25% of cases. The usual localizations of gastrinomas are at the head of the
      pancreas, the duodenal wall and the peripancreatic lymph nodes. Ectopic
      localizations, such as stomach, small bowel, gallbladder, liver or ovaries, are
      rare. We report the case of an intrahepatic gastrinoma, surgically treated by
      left hepatectomy. Upon review of scientific literature, we found 19 cases of
      intrahepatic gastrinoma. This diagnosis is always difficult to establish, even
      after a complete preoperative imaging and an extensive operative search for a
      possible primary tumor. The best evidence for diagnosis is the gastrinemia
      decreasing to a normal range after liver resection, and the absence of recurrence
      in long-term follow-up.

PMID- 19166990
TI  - Population analysis of large copy number variants and hotspots of human genetic
      disease.
AB  - Copy number variants (CNVs) contribute to human genetic and phenotypic diversity.
      However, the distribution of larger CNVs in the general population remains
      largely unexplored. We identify large variants in approximately 2500 individuals
      by using Illumina SNP data, with an emphasis on "hotspots" prone to recurrent
      mutations. We find variants larger than 500 kb in 5%-10% of individuals and
      variants greater than 1 Mb in 1%-2%. In contrast to previous studies, we find
      limited evidence for stratification of CNVs in geographically distinct human
      populations. Importantly, our sample size permits a robust distinction between
      truly rare and polymorphic but low-frequency copy number variation. We find that
      a significant fraction of individual CNVs larger than 100 kb are rare and that
      both gene density and size are strongly anticorrelated with allele frequency.
      Thus, although large CNVs commonly exist in normal individuals, which suggests
      that size alone can not be used as a predictor of pathogenicity, such variation
      is generally deleterious. Considering these observations, we combine our data
      with published CNVs from more than 12,000 individuals contrasting control and
      neurological disease collections. This analysis identifies known disease loci and
      highlights additional CNVs (e.g., 3q29, 16p12, and 15q25.2) for further
      investigation. This study provides one of the first analyses of large, rare (0.1%
      1%) CNVs in the general population, with insights relevant to future analyses of
      genetic disease.

PMID- 19166992
TI  - Evidence for the selective attention mechanism and dual-task interference.
AB  - In order to explore the selective attention mechanism and the dual-task
      information-processing model, two experiments were carried out involving a visual
      search task and a visual detection task. The results showed that the early period
      of attention selection is controlled in a bottom-up manner. With respect to the
      dual-task information-processing model, the results showed that the central
      information-processing model would include a sequence model for tasks that use
      the same perception resource, causing a bottleneck in information processing. Our
      study suggests that a simple and prominent signal could be used to attract
      drivers' attention prior to the emergent events. Moreover, any human-machine
      interface design in driving-associated systems should consider this information
      processing bottleneck. With respect to signal type, targeted and easy to
      categorize were two useful elements to consider.

PMID- 19166993
TI  - Rumination, distraction, and mindful self-focus in depressed patients.
AB  - Rumination has been proposed as a cognitive risk factor for the onset and
      maintenance of depression. In parallel, mindfulness interventions have shown to
      reduce the risk for recurrence of depressive episodes. This study aimed to
      investigate effects of short periods of induced rumination, distraction, and
      mindful self-focus on sad mood in depressed patients and to assess possible
      moderator effects of habitual variables on respective mood changes. Seventy-six
      depressed patients 3.5 years after discharge from inpatient treatment were
      subjected to negative mood induction and subsequently randomly assigned to a
      rumination, distraction, or mindful self-focus induction. Habitual aspects of
      rumination, distraction, and mindfulness were assessed by questionnaires.
      Compared to rumination, the induction of a mindful self-focus and of distraction
      showed clear beneficial effects on the course of negative mood. While habitual
      distraction predicted better mood outcomes across all conditions, patients high
      in habitual mindfulness tended to show stronger negative mood reduction
      specifically after the induction of a mindful self-focus. This study indicates
      that - similar to distraction - an experimentally induced mindful self-focus is
      able to reduce negative mood in depressed patients. Implications regarding
      possible subgroups of patients who might particularly benefit from mindfulness
      based interventions are discussed.

PMID- 19166994
TI  - Over and over again: rumination, reflection, and promotion goal failure and their
      interactive effects on depressive symptoms.
AB  - Research indicates that examining failure experiences using an immersed
      processing style versus a non-immersed, self-distanced open style influences
      cognitions about the self, motivation, and subsequent depressive symptoms.
      However, the effect of processing goal failure experiences using these different
      processing styles have not been adequately incorporated into existing self
      regulation theories of depression. In a cross-sectional study, we examined the
      interactive effects of rumination (versus reflection) and failure to attain
      promotion goals on depressive symptoms. As predicted, greater levels of promotion
      goal failure were associated with having more depressive symptoms for individuals
      who engage in moderate to high levels of rumination. In contrast, among
      individuals who engage in high levels of self-reflection, promotion goal failure
      was not associated with an appreciable increase in depressive symptoms. We
      discuss the implications of these results for self-regulatory theories of
      depression and treatments for depression.

PMID- 19166995
TI  - Carbasugar-thioether pseudodisaccharides related to N-glycan biosynthesis.
AB  - Analogues of the alpha-Glcp-(1-->3)-alpha-Glcp and alpha-Glcp-(1-->3)-alpha-Manp
      disaccharides (representing the two alpha-gluco linkages cleaved by alpha
      Glucosidase II in N-glycan biosynthesis) in which the non-reducing-end sugar is
      replaced by a carbasugar and the inter-glycosidic oxygen by a sulfur were
      synthesised. The key coupling step was an S(N)2 displacement of an equatorial
      triflate at C-1 of the carbasugar by C-3 gluco or manno thiolates with inversion
      of configuration to give thioether pseudodisaccharides with axial substitution at
      C-1 of the carbasugar. The deprotected pseudodisaccharides failed to inhibit the
      action of alpha-Glucosidase II as measured both by an in vitro assay and by free
      oligosaccharide (FOS) analysis from cell studies.

PMID- 19166997
TI  - The impact of health facilities on healthcare workers' well-being and
      performance.
AB  - The impact of health facilities on patients has been extensively researched. Yet,
      while there is a growing recognition of the need for healthy working
      environments, little is known about how health facilities affect the staff
      working in them. This paper explores how the design of health facilities impacts
      on the well-being and performance of healthcare workers. The article is based on
      a review of published literature, identified through PubMed and Google, as well
      as through searches of websites of relevant organizations. Many traditionally
      designed health facilities seem to impact negatively on the well-being of
      healthcare workers, as well as on staff recruitment, retention and performance.
      Better-designed health facilities can improve working conditions and staff
      safety, and enable staff to do their job more efficiently. The needs of
      healthcare workers should be taken into account at the initial design stage of
      health facilities, ideally though direct involvement or meaningful consultation.

PMID- 19166996
TI  - Combining TMS and fMRI: from 'virtual lesions' to functional-network accounts of
      cognition.
AB  - Transcranial magnetic stimulation (TMS) is increasingly used in Cognitive
      Neuroscience to study functional contributions of a stimulated brain region to
      cognitive and perceptual processing. TMS-related behavioural effects are often
      interpreted as reflecting selective disruption of processing primarily within the
      stimulated region itself. This approach is now being extended by studies that
      combine TMS with concurrent neuroimaging measures, such as functional magnetic
      resonance imaging (fMRI). We discuss some recent combined TMS-fMRI studies and
      their implications for TMS investigations of cognition and perception. An
      emerging theme is that TMS does not affect only the stimulated region, but can
      also influence remote brain areas interconnected with the stimulation site. Such
      'network' effects of TMS can be anatomically specific, but also context
      dependent, changing with the current functional state of the targeted network
      rather than simply reflecting just fixed, context-invariant anatomical
      connectivity. Perceptual and behavioural effects of TMS may correspondingly
      involve TMS influences on remote interconnected brain regions, not solely on the
      stimulated region itself. Thus, TMS can now be used to study the consequences of
      functional interactions between the stimulated region and other parts of the
      network. This may lead beyond strictly modular views of brain function, that
      emphasize functional properties of single brain areas, towards new perspectives
      on how functional interactions between remote but interconnected brain regions
      may support perception and cognition.

PMID- 19166998
TI  - A philosophical account of interventions and causal representation in nursing
      research.
AB  - BACKGROUND: Representing is about theories and theory formation. Philosophy of
      science has a long-standing interest in representing. At least since Ian
      Hacking's modern classic Representing and Intervening (1983) analytical
      philosophers have struggled to combine that interest with a study of the roles of
      intervention studies. With few exceptions this focus of philosophy of science has
      been on physics and other natural sciences. In particular, there have been few
      attempts to analyse the use of the notion of intervention in other disciplines
      where intervention studies are important, such as in nursing research. One
      unintended consequence of this is that the relations between representing and
      intervening tend to be less understood outside the natural sciences. OBJECTIVES
      AND DESIGN: This article highlights a number of possible topics on which nursing
      science and analytic philosophy of science can fruitfully interact. The basic
      idea is simple. Building on a characterisation of interventions in terms of (i)
      what is intervened on and (ii) with respect to what, we suggest that
      interventions in nursing research typically are a blend of varieties belonging to
      the three dimensions of agency, epistemology, and ontology. The details of the
      blend determine the relation of the particular intervention study to traditional
      representational categories such as inductivism and hypothetico-deductive method,
      and have a bearing on its explanatory power and other more theory independent
      features of research as well. The framework we suggest should be relevant for
      nurse researchers who want to adopt a more general and analytically entrenched
      perspective on representing and intervening than the methodological boundaries in
      nursing research typically allow.

PMID- 19166999
TI  - Pre-B cell colony enhancing factor (PBEF)/visfatin induces secretion of MCP-1 in
      human endothelial cells: role in visfatin-induced angiogenesis.
AB  - OBJECTIVES: Visfatin and Monocyte-Chemoattractant-Protein-1 (MCP-1) are elevated
      in cardiovascular pathologies, insulin-resistant and diabetic states. Visfatin
      has been reported to exhibit pro-angiogenic actions in human endothelial cells.
      Given MCP-1's well described pro-angiogenic properties we sought to study the
      potential interaction between visfatin and MCP-1 in human endothelial cells. We
      also explored the possible autocrine/paracrine mechanisms governing this
      potential interaction; specifically we looked at the effect of visfatin on MCP
      1's putative receptor (CCR2 receptor) in human endothelial cells. METHODS AND
      RESULTS: Using in vitro angiogenic assays (capillary tube formation and
      migration), Western blotting and RT-PCR, we found that visfatin, dose
      dependently, induced MCP-1 as well as CCR2 levels. We also studied the
      involvement of PI3Kinase, MAPKinase and NF-kappaB pathways in visfatin induced
      MCP-1/CCR2 levels by employing LY294002, U0126 and BAY11-7085, respectively. We
      found the increase in MCP-1 and CCR2 levels by visfatin were negated by LY294002
      and BAY11-7085, but not with U0126, suggesting the crucial role of PI3Kinase and
      NF-kappaB pathways in visfatin induced MCP-1 and its autocrine regulation via the
      CCR2 receptor. Finally, we consolidate the role of MCP-1 in visfatin-induced
      angiogenesis by employing CCR2 antagonist (RS-102895) and MCP-1 neutralising
      antibody, respectively. CONCLUSIONS: Our novel data reveal that MCP-1 is pivotal
      in modulating visfatin-induced angiogenesis via NF-kappaB and PI3Kinase pathways.
      Furthermore, our findings elucidate the potential influence of
      autocrine/paracrine mechanisms (via the CCR2 receptor) underlying visfatin's
      angiogenic effects through MCP-1.

PMID- 19167000
TI  - Numerical and analytical solutions for the column length-dependent band
      broadening originating from axisymmetrical trans-column velocity gradients.
AB  - Trans-column velocity gradients arising from radial variations in packing density
      or mobile phase temperature lead to a plate height contribution that, in the case
      of for example a 4.6mm column, may increase over several tens of centimeters
      before it reaches a constant value. Considering a wide variety of different trans
      column velocity profiles, including Giddings' general polynomial expression and
      several simplified partially flat profiles, and performing a set of analytical
      calculations (to establish an expression for the long time-limit constant value
      H(infinity)) and numerical simulations (to calculate the band broadening in the
      transient regime), it was found that the column length-dependent variation of
      this plate height contribution can be very closely approximated by a simple
      exponential-law expression. The availability of the latter will greatly simplify
      the experimental analysis of radial column heterogeneity effects, especially
      considering that this expression is independent of the radial dispersion, the
      column diameter, and the average velocity and maximum velocity difference.
      Surprisingly, the exponential-law expression is to a first approximation also
      independent of the shape of the velocity profile, provided the velocity profile
      does not become flat over a substantially large part of the cross-section. In the
      latter case, the transient curve obeys a more complex law, but can nevertheless
      still be approximated by an exponential-law expression, though with a different
      (larger) decay constant.

PMID- 19167001
TI  - Determining organic impurities in mother liquors from oxidative terephthalic acid
      synthesis by microemulsion electrokinetic chromatography.
AB  - In this study, a microemulsion electrokinetic chromatography (MEEKC) method was
      developed to analyze and detect several aromatic acids (benzoic acid (BA),
      isophthalic acid (IPA), terephthalic acid (TPA), p-toluic acid (p-TA), 4
      carboxylbenzaldehyde (4-CBA), trimesic acid (TSA), trimellitic acid (TMA), o
      phthalic acid (OPA), and hemimellitic acid (HMA)), which are common organic
      impurities produced by liquid-phase catalytic oxidation of p-xylene to TPA. The
      effects of microemulsion composition, column temperature, column length and
      applied voltage were examined in order to optimize the aromatic acid separations.
      This work demonstrated that variation in the concentration of surfactant (sodium
      dodecyl sulfate (SDS)) and oil phase (octane) had a pronounced effect on
      separation of the nine aromatic acids. It was also found that a decrease in
      column length had the greatest effect on shortening separation time and improving
      separation resolution for these aromatic acids when compared to that of an
      increase in column temperature or applied voltage. However, the nature and
      concentration of cosurfactants and organic modifiers were found to play only
      minor roles in the separation mechanism. Thus, a separation with baseline
      resolution was achieved within 14 min by using a microemulsion solution of pH 2.0
      containing 3.7% SDS, 0.975% octane, and 5.0% cyclohexanol; and a 50-cm capillary
      column (effective length of 40-cm) at 26 degrees C. As a result, the developed
      MEEKC method successfully determined eight impurities of aromatic acids in the
      mother liquors produced from the oxidation synthesis of TPA.

PMID- 19167002
TI  - Use of multiple-reaction monitoring ratios for identifying incompletely resolved
      fentanyl homologs and analogs via ultra-high-pressure liquid chromatography
      tandem mass spectrometry.
AB  - Fentanyl and 16 of its corresponding homologs and analogs were distinguished
      using ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC
      MS/MS). A 1.7 microm Acquity BEH C18 column (150 mm x 2.1 mm) was used with a 1%
      formic acid (pH 2.2), methanol gradient. Multiple-reaction monitoring (MRM) was
      employed for MS/MS detection. All selected fentanyl-related compounds, including
      incompletely resolved compounds, were uniquely identified using retention times
      and dual MRMs.

PMID- 19167003
TI  - Dispersive liquid-liquid microextraction combined with high-performance liquid
      chromatography-UV detection as a very simple, rapid and sensitive method for the
      determination of bisphenol A in water samples.
AB  - Dispersive liquid-liquid microextraction (DLLME) coupled with high-performance
      liquid chromatography (HPLC)-UV detection was applied for the extraction and
      determination of bisphenol A (BPA) in water samples. An appropriate mixture of
      acetone (disperser solvent) and chloroform (extraction solvent) was injected
      rapidly into a water sample containing BPA. After extraction, sedimented phase
      was analyzed by HPLC-UV. Under the optimum conditions (extractant solvent: 142
      microL of chloroform, disperser solvent: 2.0 mL of acetone, and without salt
      addition), the calibration graph was linear in the range of 0.5-100 microgL(-1)
      with the detection limit of 0.07 microgL(-1) for BPA. The relative standard
      deviation (RSD, n=5) for the extraction and determination of 100 microgL(-1) of
      BPA in the aqueous samples was 6.0%. The results showed that DLLME is a very
      simple, rapid, sensitive and efficient analytical method for the determination of
      trace amount of BPA in water samples and suitable results were obtained.

PMID- 19167004
TI  - Application of ultra-high-pressure liquid chromatography-tandem mass spectrometry
      to the determination of multi-class pesticides in environmental and wastewater
      samples. Study of matrix effects.
AB  - An ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC
      MS/MS) method for the determination of 37 pesticides (herbicides, insecticides
      and fungicides) in environmental and wastewater has been developed. To
      efficiently combine UHPLC with MS/MS, a fast-acquisition triple quadrupole mass
      analyzer was used. This analyzer (minimum dwell time, 5 ms) allows acquiring up
      to three simultaneous transitions in the selected reaction monitoring mode for
      each compound assuring a reliable identification without resolution or
      sensitivity losses. A pre-concentration step based on solid-phase extraction
      using Waters Oasis HLB cartridges (0.2 g) was applied with a 100-fold pre
      concentration factor along the whole analytical procedure. The method was
      validated based on European SANCO guidelines using surface, ground, drinking and
      treated water (from an urban solid residues treatment plant) spiked at two
      concentration levels (0.025 and 0.1 microg/L), the lowest having been established
      as the limit of quantification objective. The method showed excellent
      sensitivity, with instrumental limits of detection ranging from 0.1 to 7 pg. It
      was applied to environmental water samples (ground and surface water) as well as
      to samples of urban solid waste leachates (raw leachate and treated leachate
      after applying reversed osmosis) collected from a municipal treatment plant.
      Matrix effects have been studied in the different types of water samples
      analyzed, and several isotope-labelled internal standards have been evaluated as
      a way to compensate the signal suppression observed for most of the compounds
      studied, especially in wastewater samples. As a general remark, only those
      pesticides which response was corrected using their own isotope-labelled
      molecule, could be satisfactorily corrected in all type of samples, assuring in
      this way the accurate quantification in all matrix samples.

PMID- 19167005
TI  - Using micellar electrokinetic chromatography for the highly efficient
      preconcentration and separation of gold nanoparticles.
AB  - In this paper, we report the use of micellar electrokinetic chromatography (MEKC)
      for the highly efficient preconcentration and separation of gold nanoparticles
      (Au NPs). We used the reversed electrode polarity stacking mode (REPSM) of the
      MEKC system for the on-line enhancement and separation of the Au NPs. Several
      parameters had dramatic effects on the systems' performance, including the
      concentration of sodium dodecylsulfate (SDS) surfactant, the presence of salts in
      the NP solution, the pH of the running electrolyte, and the temperature of the
      capillary. Under the optimized conditions [buffer: SDS (70 mM) and 3
      cyclohexylamino-1-propanesulfonic acid (CAPS; 10 mM) at pH 10.0; applied voltage:
      20 kV; operating temperature: 25 degrees C; additive: sodium dihydrogenphosphate
      (NaH(2)PO(4), 10 mM); REPSM strategy for sample preconcentration], the number of
      theoretical plates for the 5.3- and 40.1-nm-diameter Au NPs were 3000 and (an
      ultrahigh) 2.1 x 10(6), respectively; in addition, the detection sensitivities
      toward the Au NPs were enhanced ca. 20- and 380-fold, respectively, relative to
      those obtained using standard MEKC analysis conditions. Furthermore, monitoring
      the electropherograms using diode-array detection allowed us to identify and
      characterize the sizes of the separated NPs from their UV-vis spectra. Our
      findings suggest that MEKC is a highly efficient tool for both the
      preconcentration and separation of NPs.

PMID- 19167006
TI  - Development of a screening method to determine the pattern of fermentation
      metabolites in faecal samples using on-line purge-and-trap gas chromatographic
      mass spectrometric analysis.
AB  - An on-line screening method to analyse volatile organic compounds (VOCs) in
      faecal samples was developed. VOCs were isolated from a standard solution or
      faecal samples using a purge-and-trap system and identified and quantified by GC
      MS. The experimental conditions were optimised and the performance of the system
      was evaluated. Linear calibration curves were obtained with correlation
      coefficients of at least 0.992. RSDs within and between days were less than 10%.
      The method was successfully applied to the analysis of faecal samples, yielding
      135 different volatile organic compounds identified in 11 faecal samples. Of
      those, 22 VOCs were found in all volunteers, whereas 34 VOCs were person
      specific.

PMID- 19167007
TI  - Lysozyme mediated calcium carbonate mineralization.
AB  - Lysozyme, a major component of egg white proteins, has been speculated to
      participate in the calcification of avian eggshells. However, its detailed role
      during the eggshell formation is not well understood. In this work, the influence
      of lysozyme on the precipitation of CaCO(3) has been investigated using a
      combined study of FTIR, XRD, and SEM. The precipitation was produced from
      (NH(4))(2)CO(3) vapor diffusion into CaCl(2) aqueous solution using a specially
      built chamber. In the absence of lysozyme, hexagonal platelets of vaterite and
      their spherical aggregates dominated the precipitates during the first 3-12 h
      crystallization period studied, with the (001) crystal face well expressed in the
      hexagonal direction. In contrast, calcite was favored to precipitate in the
      presence of lysozyme during the same period and the effect was found to be
      proportional to lysozyme concentration. Furthermore, the (110) face of calcite
      was expressed in addition to the common (104) face, and the morphological
      modification was also lysozyme concentration dependent. We attributed these
      phenomena to the selective adsorption of ammonium ions and lysozyme onto
      different crystal faces. Our findings have clearly revealed the concentration and
      face dependent role of lysozyme in CaCO(3) precipitation. This, together with the
      abundance of lysozyme in the uterine fluid, implies its direct contribution to
      the hierarchical structures of calcite during the initial stage of eggshell
      formation.

PMID- 19167009
TI  - Thermodynamic cycle analysis for capacitive deionization.
AB  - Capacitive deionization (CDI) is an ion removal technology based on temporarily
      storing ions in the polarization layers of two oppositely positioned electrodes.
      Here we present a thermodynamic model for the minimum work required for ion
      separation in the fully reversible case by describing the ionic solution as an
      ideal gas of pointlike particles. The work input is fully utilized to decrease
      the entropy of the outflowing streams compared to that of the inflow. Based on
      the Gouy-Chapman-Stern (GCS) model for planar diffuse polarization layers-with
      and without including additional ion volume constraints in the diffuse part of
      the double layer-we analyze the electric work input during charging and the work
      output during discharging, for a reversible charging-discharging cycle. We
      present a graphical thermodynamic cycle analysis for the reversible net work
      input during one full cycle of batchwise operation of CDI based on the charge
      voltage relations for different ionic strengths. For the GCS model, an analytical
      solution is derived for the charge efficiency Lambda, which is the number of salt
      molecules removed per electron transferred from one electrode to the other. Only
      in the high voltage limit and for an infinite Stern layer capacity does Lambda
      approach unity.

PMID- 19167008
TI  - Surface-enhanced Raman scattering of hydroxybenzoic acids adsorbed on silver
      nanoparticles.
AB  - Surface-enhanced Raman scattering (SERS) of hydroxybenzoic acids has been studied
      on silver sols in H(2)O and D(2)O solutions. The adsorption behavior of 4
      hydroxybenzoic acid (4HBA) is different from that of salicylic (2HBA) and 3
      hydroxybenzoic (3HBA) acids. It was concluded that 4HBA is adsorbed on silver
      nanoparticles (Ag(n)) as either oxidobenzoate (A(2-)) or hydroxybenzoate (A(-)),
      depending on the pH of the solution, given rise to a flat orientation. Both 2HBA
      and 3HBA acids are always adsorbed as hydroxybenzoates anions (A(-)) at pH >or=5
      and link to the metal through the carboxylate group (Ag(n)--A(-)), standing more
      or less perpendicular to the metal surface. In the case of these monoanions, the
      selective enhancement of the bands is due mainly to a resonant electron or charge
      transfer process (ET or CT) from the metallic nanoparticles to the adsorbates,
      yielding the transient formation of the respective radical dianions (Ag(+)(n)-
      A(2-)). It is found that the enhanced bands, and especially the mode 8a;nu(ring),
      are related to the difference between the equilibrium structures of the adsorbate
      in its ground (A(-)) and CT-excited (A(2-)) states. In the SERS spectrum of 4HBA
      dianion, the contribution of CT mechanism is not observed.

PMID- 19167010
TI  - Simulation of the QRS complex using papillary muscle positions as the site of
      early activation in human subjects.
AB  - BACKGROUND: Simulation of the electrical activation of the heart and its
      comparison with real in vivo activation is a promising method in testing
      potential determinants of excitation. Simulation of the electrical activity of
      the human heart is now emerging as a step forward for understanding and
      predicting electrophysiologic patterns in humans. Initial points of excitation
      and the manner in which the activation spreads from these points are important
      variables determining QRS complex characteristics. It has been suggested that in
      humans, the initial excitation of the left ventricle is a primary determinant of
      QRS complex characteristics, and that excitation begins at the papillary muscles
      and septum, where the fascicles of the left bundle branch insert. The aim of this
      study is to test the hypothesis that QRS duration and direction of QRS axis in
      the frontal plane have excellent agreement between real QRS and simulated QRS
      using papillary muscle position to indicate the border of the origin of early
      ventricular activation. METHODS: Fourteen healthy adult volunteers were included
      in the study. Magnetic resonance imaging data were obtained to assess the
      papillary muscle positions. Twelve-lead electrocardiographic (ECG) recordings
      were used to obtain real ECG data for assessment of QRS duration and QRS axis in
      each subject. Simulation software developed by ECG-TECH Corp (Huntington, NY) was
      used to simulate the ECG of each subject to determine simulated QRS duration and
      QRS frontal plane axis. QRS duration and QRS axis data were compared between
      simulated and real ECG and agreement between these variables was calculated.
      RESULTS: Seventy-nine percent of subjects had a difference of the QRS duration
      between real and simulated ECG of less than 10 milliseconds. The calculated
      strength of agreement between simulated and real QRS duration was 71% and
      considered as "good" (kappa statistics). In 70% of subjects, the difference in
      the QRS axis was less than 10 degrees . The calculated strength of agreement
      between simulated and real QRS axis was 80% and considered as "excellent" (kappa
      statistics). CONCLUSIONS: The results of this study suggest that the sites of the
      initiation of electrical activity in the left ventricle, as assessed by the
      positions of papillary muscles, may be considered as primary determinants of the
      QRS duration and QRS axis in humans. This knowledge may help in predicting normal
      QRS characteristic on a patient-specific basis. In this study, simulation of the
      QRS complex was based on papillary muscles from human hearts.

PMID- 19167011
TI  - Predicting the culprit artery in acute ST-elevation myocardial infarction and
      introducing a new algorithm to predict infarct-related artery in inferior ST
      elevation myocardial infarction: correlation with coronary anatomy in the HAAMU
      Trial.
AB  - AIMS: The objective of this study is to predict the culprit artery from the
      electrocardiogram (ECG) by predefined criteria and to compare a new algorithm
      with a previous one for predicting the culprit artery in inferior ST-elevation
      myocardial infarction (STEMI). METHODS AND RESULTS: In "all-comers" (n = 187)
      with acute STEMI, with ECG and angiography from the acute phase, the positive and
      negative predictive values for the prediction of the left anterior descending
      coronary artery, left circumflex coronary artery, or right coronary artery as the
      infarct-related artery were 96% and 96%, 65% and 95%, 92% and 97%, respectively.
      In inferior STEMI (n = 98), positive and negative predictive values to predict
      the right coronary artery or the left circumflex coronary artery as the culprit
      artery were 92% and 75% and 75% and 94%, respectively. CONCLUSIONS: In "all
      comers" with STEMI, the culprit artery could be predicted by ECG criteria with
      high predictive values. In inferior STEMI, a new algorithm for culprit artery
      prediction was successfully tested.

PMID- 19167012
TI  - ST-segment resolution assessed immediately after primary percutaneous coronary
      intervention correlates with infarct size and left ventricular function in
      cardiac magnetic resonance at 1-year follow-up.
AB  - BACKGROUND: Little is known about the predictive value of electrocardiographic ST
      segment resolution (STR) assessed immediately after primary percutaneous coronary
      intervention (PCI). The aim of the study was to analyze the value of STR and
      maximum single-lead ST-segment elevation assessed immediately after primary PCI
      in prediction of infarct size and left ventricular function in cardiac magnetic
      resonance (CMR) at 1-year follow-up. METHODS AND RESULTS: A total of 28 patients
      with anterior wall ST-segment elevation myocardial infarction treated with
      primary PCI entered the study. There was a significant correlation of STR and
      maximum single-lead ST-segment elevation assessed immediately after primary PCI
      and CMR infarct size and left ventricular function after 1 year. When analyzed
      according to standard optimal reperfusion cutoff (70% for STR and 1 mm for single
      lead elevation), both electrocardiographic parameters were also good predictors
      of CMR infarct size and left ventricular function after 1 year. CONCLUSIONS: ST
      segment resolution and the single-lead maximum ST-segment elevation assessed
      immediately after primary PCI for ST-segment elevation myocardial infarction are
      good predictors of infarct size and left ventricular function in 1-year follow
      up.

PMID- 19167013
TI  - Mechanisms of very-low-voltage waveforms in either lead I, II, or III.

PMID- 19167014
TI  - Aligning body and world: stable reference frames improve young children's search
      for hidden objects.
AB  - This study investigated how young children's increasingly flexible use of spatial
      reference frames enables accurate search for hidden objects by using a task that
      3-year-olds have been shown to perform with great accuracy and 2-year-olds have
      been shown to perform inaccurately. Children watched as an object was rolled down
      a ramp, behind a panel of doors, and stopped at a barrier visible above the
      doors. In two experiments, we gave 2- and 2.5-year-olds a strong reference frame
      by increasing the relative salience and stability of the barrier. In Experiment
      1, 2.5-year-olds performed at above-chance levels with the more salient barrier.
      In Experiment 2, we highlighted the stability of the barrier (or ramp) by
      maximizing the spatial extent of each reference frame across the first four
      training trials. Children who were given a stable barrier (and moving ramp)
      during these initial trials performed at above-chance levels and significantly
      better than children who were given a stable ramp (and moving barrier). This work
      highlights that factors central to spatial cognition and motor planning-aligning
      egocentric and object-centered reference frames-play a role in the ramp task
      during this transitional phase in development.

PMID- 19167015
TI  - Children's understanding of addition and subtraction concepts.
AB  - After the onset of formal schooling, little is known about the development of
      children's understanding of the arithmetic concepts of inversion and
      associativity. On problems of the form a+b-b (e.g., 3+26-26), if children
      understand the inversion concept (i.e., that addition and subtraction are inverse
      operations), then no calculations are needed to solve the problem. On problems of
      the form a+b-c (e.g., 3+27-23), if children understand the associativity concept
      (i.e., that the addition and subtraction can be solved in any order), then the
      second part of the problem can be solved first. Children in Grades 2, 3, and 4
      solved both types of problems and then were given a demonstration of how to apply
      both concepts. Approval of each concept and preference of a conceptual approach
      versus an algorithmic approach were measured. Few grade differences were found on
      either task. Conceptual understanding was greater for inversion than for
      associativity on both tasks. Clusters of participants in all grades showed that
      some had strong understanding of both concepts, some had strong understanding of
      the inversion concept only, and others had weak understanding of both concepts.
      The findings highlight the lack of developmental increases and the large
      individual differences in conceptual understanding on two arithmetic concepts
      during the early school years.

PMID- 19167016
TI  - Does the endogenous opiate system play a role in the Restless Legs Syndrome? A
      pilot post-mortem study.
AB  - Opioids are an effective treatment for the signs and symptoms of Restless Legs
      Syndrome (RLS) and the signs and symptoms of RLS return when the opiate receptor
      blocker naloxone is given to opioid treated RLS patients in a blinded fashion.
      These data suggest that the opioid effect is specific to the opiate receptor in
      RLS and implicate the endogenous opioid system with its enkephalins and
      endorphins in the pathogenesis of RLS. We therefore measured Beta endorphin, Met
      enkephalin and Leu-enkephalin levels in thalamus and substantia nigra of RLS
      patients (5 F - avg age 80.2 years) compared to controls (5 F, 1 M - avg age 76.3
      years). One half of each brain was fixed in paraformaldehyde (PFA) in phosphate
      buffered saline (PBS) for pathologic evaluation and paraffin sections were
      stained with antibodies. Cell numbers were counted in a blinded fashion. In the
      thalamus, there were reductions of Beta-endorphin and Met-enkephalin positive
      cells by 37.5% (p=.006, effect size 2.16) and 26.4% (p=.028, effect size 1.58),
      respectively, in RLS patients compared to controls. There was no difference in
      Leu-enkephalin in the thalamus or changes in Beta endorphin, Met-enkephalin, Leu
      enkephalin or Tyrosine Hydroxylase, the rate limiting step for dopamine
      synthesis, in the substantia nigra. Although one of the main hypotheses for
      pathogenesis has been that there is a dopaminergic hypofunction in RLS, this lack
      of decrease in Tyrosine Hydroxylase in substantia nigra is consistent with
      previously published post-mortem data in RLS. With Bonferroni correction, the
      decrease in thalamic Beta endorphin remained significant (p= .006 x 7= .042).
      These results suggest that there may be altered central processing of pain in RLS
      and these data further implicate the endogenous opioid system in the pathogenesis
      of RLS. The mu opiate receptor subtype may be involved in the pathogenesis of RLS
      as it is the target of Beta-endorphin and Met-enkephalin but not Leu-enkephalin.
      However, these results should be viewed as only preliminary and more advanced
      techniques such as stereology should be employed in future post-mortem studies.
      In addition, other opioid rich areas need to be explored as well as areas
      implicated in the pathogenesis of RLS such as the red nucleus and raphe nucleus.

PMID- 19167017
TI  - Ketamine inhibits the phagocytic responses of canine peripheral blood
      polymorphonuclear cells through the upregulation of prostaglandin E2 in
      peripheral blood mononuclear cells in vitro.
AB  - Ketamine has been reported to decrease the immune functions of phagocytes.
      Previously, we observed that the phagocytic capacity and oxidative burst activity
      (OBA) of canine peripheral blood polymorphonuclear cells (PMNs) were inhibited by
      the supernatant from canine peripheral blood mononuclear cells (PBMCs) cultures
      treated with ketamine. In the present study, we examined whether in vitro
      treatment with ketamine modulates prostaglandin E(2) (PGE(2)) production in
      PBMCs. Treatment with ketamine or with ketamine-treated PBMCs culture supernatant
      simultaneously decreased the phagocytic capacity and OBA of PMNs. Ketamine
      increased PGE(2) production by PBMCs. Recombinant PGE(2) decreased the phagocytic
      capacity and OBA of PMNs. AH-6809, an E-prostanoid 2 (EP2) antagonist, restored
      the phagocytic capacity and OBA of PMNs, decreased by either the ketamine-treated
      PBMCs culture supernatant or recombinant PGE(2). These results suggest that
      ketamine inhibits the phagocytic responses of canine PMNs, and that this results
      from the increase in PGE(2) produced by canine PBMCs.

PMID- 19167018
TI  - Nitrous oxide emissions for early warning of biological nitrification failure in
      activated sludge.
AB  - Experiments were carried out to establish whether nitrous oxide (N2O) could be
      used as a non-invasive early warning indicator for nitrification failure. Eight
      experiments were undertaken; duplicate shocks DO depletion, influent ammonia
      increases, allylthiourea (ATU) shocks and sodium azide (NaN3) shocks were
      conducted on a pilot-scale activated sludge plant which consisted of a 315 L
      completely mixed aeration tank and 100 L clarifier. The process performed well
      during pre-shock stable operation; ammonia removals were up to 97.8% and N2O
      emissions were of low variability (<0.5 ppm). However, toxic shock loads produced
      an N2O response of a rise in off-gas concentrations ranging from 16.5 to 186.3
      ppm, followed by a lag-time ranging from 3 to 5 h ((0.43-0.71) x HRT) of
      increased NH3-N and/or NO2(-) in the effluent ranging from 3.4 to 41.2 mg L(-1).
      It is this lag-time that provides the early warning for process failure, thus
      mitigating action can be taken to avoid nitrogen contamination of receiving
      waters.

PMID- 19167019
TI  - Adsorption effect on the degradation of 4,6-o-dinitrocresol and p-nitrophenol in
      a montmorillonite clay slurry by AFT.
AB  - The adsorption and degradation of 4,6-o-dinitrocresol (DNOC) and p-nitrophenol
      (PNP) in SWy-2 montmorillonite clay slurry were investigated. The pH and type of
      cation of the slurry were varied. Results showed that adsorption of DNOC and PNP
      increased at lower pH values, and when pH < pKa(4.4) of DNOC, DNOC was almost
      completely adsorbed on the clay under given experimental conditions. The specific
      cation also had a significant effect on adsorption, which was dramatically
      enhanced in the presence of K+ and NH4+, compared with the presence of Na+ or
      Ca2+. Anodic Fenton treatment (AFT) degradation of DNOC and PNP in the clay
      slurry was studied, and it was found that DNOC degradation rates were greatly
      affected by the initial pH and the types of electrolytes. Due to the higher
      adsorption, the degradation rate substantially decreased in the clay slurry
      system in the presence of K+ and low pH, with a large amount of DNOC residue
      remaining after 60 min treatment. AFT degradation of PNP was completed within 30
      min treatment. Based on LC-MS data, a DNOC degradation pathway was proposed.
      Overall, the results showed the inhibition effect of adsorption on the
      degradation of nitroaromatic compounds in montmorillonite clay slurry by AFT,
      providing important implications for water and soil remediation.

PMID- 19167020
TI  - Fate of 4-nonylphenol in a biosolids amended soil.
AB  - The fate of the endocrine disrupting compound 4-nonylphenol (NP) in an
      agricultural soil amended with biosolids was assessed in a greenhouse study. A
      biosolids with a total NP concentration of 900 mg kg(-1) was incorporated into
      the 4 cm surface layer of soil columns at an agronomic rate equivalent to 1.7 kg
      m(2). Half of the columns were planted with Triticum aestivum L., red hardy
      winter wheat seeds, whereas the remaining columns were unplanted to evaluate the
      influence of plant growth on the fate of NP. The degradation of total NP and
      eight NP isomers was monitored over 45 d. The half-life of NP in this soil system
      ranged from 16 to 23 d depending on treatment. After 45 d from the start of the
      trail, 15% of the initial biosolids-NP remained in the planted columns, whereas
      approximately 30% remained in the unplanted columns, indicating enhanced
      degradation in the presence of plants. The eight NP isomers exhibited different
      degradation rates, but minimal amounts of all isomers persisted after 45 d.
      Movement of NP below the zone of incorporation was slight (<2% of total NP
      present at any sampling interval) and no NP was detected in column leachates or
      in wheat leaves.

PMID- 19167021
TI  - Transcriptional effects of nonylphenol, bisphenol A and PBDE-47 in liver of
      juvenile Atlantic cod (Gadus morhua).
AB  - The transcriptional levels of 10 genes were quantified in liver of Atlantic cod
      exposed to environmental relevant concentrations of three model toxicants; two
      alkylphenols (30 microg/L nonylphenol (NP) and 50 microg/L bisphenol A (BPA)) and
      one brominated flame-retardant congener (5 microg/L PBDE-47). The fish were
      exposed to the toxicants for 3 weeks, with n=6 in each group (a total of 24 fish
      were used). NP exposure produced a significant reduction of five CYPs genes
      (CYP1A (P<0.01), CYP2C33-like (P<0.001), CYP2Y3 (P<0.001), CYP2P1-like (P<0.01)
      and CYP3C1-like (P<0.01)). A significant reduction was also seen for three CYPs
      after BPA exposure (CYP2C33-like, CYP2Y3 and CYP3C1-like (P<0.01 for all)). PBDE
      47 exposure produced a significant reduction of CYP1A, CYP2C33-like and CYP3C1
      like (P<0.05 for all). The genes encoding Phase II enzymes responded in a
      different manner; NP exposure resulted in a 4.6-fold increase of GST pi
      (P<0.001), whereas BPA exposure gave no effects on these enzyme genes. PBDE-47
      exposure resulted in a 3.3-fold reduction of UGT (P<0.05). No effects were seen
      on the antioxidant genes GSH-Px and GR for any of the three toxicants. Thus, all
      three toxicants seem to down regulate several CYPs, giving rise to distinct mRNA
      expression patterns suggesting that these toxicants act on the same receptors or
      via the same pathways.

PMID- 19167022
TI  - Development of a feeding behavioural bioassay using the freshwater amphipod
      Gammarus pulex and the Multispecies Freshwater Biomonitor.
AB  - The present study reports the development of a feeding behavioural bioassay using
      the Multispecies Freshwater Biomonitor (MFB). This device is based on the
      quadruple impedance conversion technique to record online different behaviours of
      animals. Animal movements in the water generate specific frequencies, and the MFB
      can estimate the percentage of time producing each frequency (from 0.5 to 8.5 Hz)
      by means of a stepwise discrete Fourier transformation. Two feeding behavioural
      bioassays were conducted in order to know the frequencies related to feeding
      behaviour of the freshwater amphipod Gammarus pulex. The first bioassay assessed
      the effects of food presence in the amphipod behaviour. The second bioassay
      assessed the effects of cadmium on the feeding activity (measured as leaf weight
      loss) and behaviour (swimming, ventilation, and feeding recorded through the MFB)
      of G. pulex in order to check the suitability of the developed method. The
      results of the first bioassay showed that the frequencies ranging from 3.0 to 4.5
      Hz were highly correlated with feeding activity, especially 3.5 and 4.0 Hz. In
      the second bioassay, we found that cadmium reduced feeding and ventilation
      behaviours. Our study showed that the MFB can be used to record the feeding
      behaviour of G. pulex exposed to toxicants. The developed feeding behavioural
      bioassay allows an accurate and automatic assessment of several endpoints,
      including feeding, swimming and ventilation. However, the study of the complex
      behaviour of G. pulex using the MFB needs further research, since some behaviours
      seem to generate similar frequencies.

PMID- 19167023
TI  - Seasonal variation of total and biochemically available concentrations of PAHs in
      a floodplain lake sediment has no effect on the benthic invertebrate community.
AB  - Floodplain areas in the Netherlands are moderately to heavily contaminated with
      trace metals and organic contaminants. The impact of this sediment pollution on
      benthic invertebrates is best described with so-called 'bioavailable'
      concentrations instead of total concentrations. Studies into the effect of
      contaminants on biota are usually a snapshot in time, with one or two samples in
      a year. In such studies, effect of seasonal variation cannot be detected.
      Objective of this study was to investigate the temporal variation of sediment PAH
      contamination in one floodplain lake, and possible consequences for the benthic
      invertebrate community. This was done by sampling biota, abiotic variables and
      sediment contaminants every four weeks during one year. We observed a limited
      seasonal variation in total and bioavailable concentrations of PAHs. Multivariate
      analysis revealed that the PAH contamination is not a significant factor for the
      benthic invertebrate community in this floodplain lake. Bioavailable
      concentrations of PAHs were low and no effects could be expected based on the
      measured values. No increase of available PAHs was observed in periods where
      conditions for degradation were absent (low temperature, anaerobic). These
      results also indicate that in such floodplain lake systems, with historical
      pollution, the timing of sampling to assess sediment contamination with organic
      pollutants is of limited importance. This can be useful for planning sampling in
      risk assessment studies.

PMID- 19167024
TI  - Monitoring lichen recolonization on a restored calcareous statue.
AB  - Monitoring lichens on monuments can have different purposes, one of which is
      monitoring the effectiveness of restoration. In the present work, lichen
      recolonization on a calcareous statue was monitored for evaluating the long-term
      effectiveness of restoration in preventing new biological growth. Species
      richness and composition of lichen communities from three surveys (one pre
      restoration and two post-restoration) covering a twelve years period, are
      compared. The long-term effectiveness of the restoration of the statue was low,
      and even the use of water repellents failed in avoiding lichen recolonization.
      The short durability of the treatment applied to the statue was also confirmed by
      the recolonization pattern which seemed more related to the geometry of the
      statue than to the hydrorepellence of its surface. Recolonization involved lichen
      communities which differed from those covering the statue before restoration.
      Some species were significantly associated with each step of the succession, as
      well as to pre-restoration conditions. The pre-restoration lichen community was
      more differentiated across the statue, indicating a complex "Statue Ecosystem"
      that is perhaps more typical of a later successional stage. On the contrary, only
      a few communities dominated by a few species were involved in the recolonization.
      The management of stoneworks exposed in the parks of villas could be more
      effective focusing on maintenance than on repeated cleaning or restoration, whose
      effects are hindered by practical difficulties in preventing the causes of
      biological growth. If restorations are not going to be maintained, it would be
      better to retain a more historic, diverse, and complex lichen community than a
      simplified community of "weedy" lichens that quickly cover almost the same area
      as the pre-restoration community did. With this perspective, in the environmental
      and artistic context of these parks, biodiversity should be included in the
      concept of the historic and artistic value of the artworks.

PMID- 19167025
TI  - Heavy metal mobility in intertidal sediments of the Scheldt estuary: Field
      monitoring.
AB  - The current paper aims to check whether the factors affecting metal mobility in
      intertidal sediments and floodplain soils of the river Scheldt, as identified
      under controlled greenhouse conditions in previous studies, also play a similar
      role under variable field conditions. Moreover, we aimed to assess the importance
      of these factors as a function of sampling time and depth, with respect to the
      natural variations in water table levels. This field monitoring revealed that the
      mobility of metals in intertidal sediments of the Scheldt estuary indeed are
      affected by factors which were identified to affect the metal fate in the upper
      sediment layer in previous greenhouse experiments. However, the effects were
      often less pronounced under field conditions. This can be attributed to the lower
      sampling resolution, the occurrence of interactions between factors, the
      disturbance of microbial communities during setup of greenhouse experiments and
      the more moderate environmental conditions in the field, affecting microbial and
      enzymatic activities. At most of the sampled wetlands, the level of the water
      table fluctuated only slightly during fall, winter and spring, whereas it
      decreased substantially during summer, especially at the sites with more sandy
      sediments. The highest sulphide concentrations were found at the sites where the
      water table level never decreased considerably. These sulphides primarily
      suppress the availability of Cd, Cu, Ni and Zn. Organic complexation resulted in
      the mobilisation of Cu, Ni and Cr. The concentrations of Cd, Ni and Zn in the
      pore water were affected by Fe/Mn oxide reduction, whereas Cd and Zn
      concentrations appeared to be also affected by the salinity.

PMID- 19167026
TI  - Risk assessment of exposure to volatile organic compounds in groundwater in
      Taiwan.
AB  - The purpose of this study is to assess the risks from exposure to 14 volatile
      organic compounds (VOCs) in selected groundwater sites in Taiwan. The study
      employs the multimedia environment pollutant assessment system (MEPAS) model to
      calculate the specific non-cancer and cancer risks at an exposure level of 1
      microg/L of each VOC for a variety of exposure pathways. The results show that
      the highest specific non-cancer risk is associated with water ingestion of vinyl
      chloride (VC) and that the highest specific cancer risk is associated with indoor
      breathing of VC. The three most important exposure pathways for risk assessment
      for both non-cancer and cancer risks are identified as water ingestion, dermal
      absorption when showering, and indoor breathing. Excess tetrachloroethylene
      (PCE), trichloroethylene (TCE), dichloroethylene (DCE), and VC are detected in
      the groundwater aquifers of one dump site and one factory. However, the study
      suggests that the pollutants in the contaminated groundwater aquifers do not
      travel extensively with groundwater flow and that the resulting VOC
      concentrations are below detectable levels for most of the sampled drinking-water
      treatment plants. Nevertheless, the non-cancer and cancer risks resulting from
      use of the contaminated groundwater are found to be hundred times higher than the
      general risk guidance values. To ensure safe groundwater utilisation, remediation
      initiatives for soil and groundwater are required. Finally, the study suggests
      that the current criteria for VOCs in drinking water might not be capable of
      ensuring public safety when groundwater is used as the primary water supply; more
      stringent quality criteria for drinking water are proposed for selected VOCs.

PMID- 19167027
TI  - Mercury speciation in the Valdeazogues River-La Serena Reservoir system:
      influence of Almaden (Spain) historic mining activities.
AB  - Mercury (Hg) speciation and partitioning have been investigated in a river
      reservoir system impacted by the Almaden mining activities, the world's largest
      Hg district. This study is the first to simultaneously investigate Hg dynamics
      from above the mining district and into the La Serena Reservoir (3219 Hm(3)),
      being the third largest reservoir in Europe and the largest in Spain. Water,
      sediment and biota were sampled at different seasons during a 2-year study from
      the Valdeazogues River, which flows east-west from the mining District, to La
      Serena Reservoir. Simultaneously, a comprehensive study was undertaken to
      determine the influence of some major physico-chemical parameters that
      potentially influence the fate of Hg within the watershed. Concentrations of
      dissolved Hg in water were below 0.14 microg/L, whereas particulate Hg ranged
      from 0.1 to 87 microg/g, with significant seasonal variation. Total Hg
      concentrations varied from 7 to 74 microg/g in sediment from the Valdeazogues
      River, while in sediments from La Serena Reservoir were below 2 microg/g. On the
      other hand, methyl-Hg reached concentrations up to 0.3 ng/L in water and 6 ng/g
      in sediment from La Serena Reservoir, whereas maximum concentrations in
      Valdeazogues River were 5 ng/L and 880 ng/g in water and sediment, respectively.
      The distribution of Hg species in the Valdeazogues River-La Serena Reservoir
      system indicated a source of Hg from the mine waste distributed along the river.
      Total Hg in water was strongly correlated with total dissolved solids and
      chlorophyll a concentrations, whereas organic carbon and Fe concentrations seem
      to play a role in methylation of inorganic Hg in sediment. Total Hg
      concentrations were low in fish from Valdeazogues River (0.8-8.6 ng/g, wet
      weight) and bivalves from La Serena Reservoir (10-110 ng/g, wet weight), but most
      was present as methyl-Hg.

PMID- 19167028
TI  - Management and investigation of neonatal thromboembolic events: genetic and
      acquired risk factors.
AB  - Newborns comprise the largest group of children developing thromoboembolic events
      (TE(S)), due to the peculiarities of their developmental hemostatic system.
      Moreover, in the sick newborn, especially preterm, numerous acquired perinatal
      and iatrogenic conditions might result in a disturbance between coagulation and
      fibrinolysis, leading to thrombus formation. Nevertheless, the contribution of
      acquired prothrombotic disorders in the pathogenesis of thromboembolic disease in
      newborns remains poorly defined. Few data are currently available regarding the
      influence of maternal or fetal genes on thrombotic risk in the fetus and neonate.
      Ongoing National and International registries are partially answering these
      questions. The purpose of this review is to evaluate the current knowledge about
      the role of inherited, acquired perinatal and maternal prothrombotic risk factors
      in neonatal cerebral nervous system (CNS) thrombotic events and non-CNS
      thrombotic events.

PMID- 19167030
TI  - Nomogram underestimates 10-year survival in healthy men selected for radical
      prostatectomy at age 70 years or older.
AB  - OBJECTIVES: To externally review a nomogram developed to predict the 10-year
      survival probability of men selected for radical prostatectomy. METHODS: A total
      of 1910 consecutive patients who underwent radical prostatectomy from 1992 to
      2004 were studied. The mean age was 64.2 years; the mean follow-up for the
      surviving patients was 6.3 years. The patients were classified according to age
      and the Charlson comorbidity score. The 10-year survival probability was
      estimated for each individual patient, applying a recently published nomogram
      incorporating these 2 variables. The survival rates estimated by the Kaplan-Meier
      method and the mean values of the nomogram-predicted survival probabilities were
      compared using 1-sample Wald tests. Subgroup analyses were done after
      stratification by age and Charlson score. RESULTS: Even including the prostate
      cancer-related mortality (accounting for 5.1% at 10 years), the 10-year overall
      survival rate in our sample was somewhat greater than predicted by the nomogram
      (84.9% vs 81.9%, P = .0222). Subgroup analyses revealed that this difference was
      attributable to a greater than predicted survival in patients with a Charlson
      score of 0 and aged > or = 70 years (87.9% vs 74.7%, P < .0001). In contrast, in
      the other subgroups, the predicted and Kaplan-Meier estimated survival rates did
      not differ meaningfully. CONCLUSIONS: Clinicians using this nomogram should be
      aware of a possible underestimation of survival in healthy men aged > or = 70
      years selected for radical prostatectomy.

PMID- 19167031
TI  - Association of sexual dysfunction with lower urinary tract symptoms of BPH and
      BPH medical therapies: results from the BPH Registry.
AB  - OBJECTIVES: The severity of lower urinary tract symptoms (LUTS) has correlated
      with erectile dysfunction (ED) and ejaculatory dysfunction (EjD) in large-scale
      epidemiologic studies. ED and EjD are also side effects of some medical therapies
      for LUTS suggestive of benign prostatic hyperplasia (LUTS/BPH). These
      relationships were examined in a physician office-based population of men
      enrolled in the BPH Registry. METHODS: Enrolled men with LUTS/BPH who completed
      the International Prostate Symptom Score (IPSS), IPSS bother question, 5-item
      International Index of Erectile Function, and the 3 ejaculatory function items of
      the Male Sexual Health Questionnaire-EjD short form at baseline were eligible.
      The relationship between sexual dysfunction and LUTS/BPH and BPH medical
      therapies were examined using multivariate analyses. RESULTS: Of 6924 men
      enrolled, 5042 (mean age 65 years) completed all 4 baseline assessments. Of 3084
      sexually active men, age, total IPSS, IPSS bother score, hypertension, diabetes,
      and black race/ethnicity were independent predictors of both ED and EjD (all P <
      .05). For the subset of 1362 men receiving BPH medical therapy, a significant
      association (P < .0001) was demonstrated for ED and EjD with specific BPH medical
      therapies. The alpha(1A)-subtype nonsuperselective quinazoline alpha(1)-blockers
      alfuzosin, doxazosin, and terazosin appeared to be associated with better
      ejaculatory function than were the alpha(1A)-subtype superselective sulfonamide
      alpha(1)-blocker tamsulosin, 5alpha-reductase inhibitors, and alpha(1)-blocker
      plus 5alpha-reductase inhibitor combination therapy. CONCLUSIONS: These results
      have provided additional evidence of the link between LUTS/BPH and sexual
      dysfunction in aging men and support clinical trial results indicating different
      rates of sexual side effects for BPH medical therapies.

PMID- 19167032
TI  - Angiotensin II type 1 receptor antagonist enhances cis-dichlorodiammineplatinum
      induced cytotoxicity in mouse xenograft model of bladder cancer.
AB  - OBJECTIVES: To examine whether candesartan enhances the cytotoxicity of cis
      dichlorodiammineplatinum (CDDP) in mice with bladder cancer as a method to
      enhance the therapeutic effects of CDDP. CDDP is an antitumor agent
      conventionally used against bladder cancer; however, its therapeutic efficacy
      appears to not be fully satisfactory. Recent studies have shown the antitumor
      activity of the angiotensin II type 1 receptor antagonist candesartan. METHODS: A
      xenograft model was prepared in nude mice using human bladder cancer cells (KU-19
      19). Candesartan (1 mg/kg/d) was administered daily by oral gavage from the day
      of implantation plus 28 days, and CDDP (1 mg/kg/d) was administered
      intraperitoneally from days 5 to 9. The microvessel density, vascular endothelial
      growth factor expression, and apoptosis were investigated immunohistochemically.
      RESULTS: Candesartan, CDDP, and candesartan-CDDP suppressed tumor growth to
      41.9%, 33.8%, and 13.2%, respectively, of the tumor volume in the control group,
      showing that combined treatment significantly inhibited tumor growth compared
      with each single agent alone. The microvessel density was significantly decreased
      in the candesartan and candesartan-CDDP groups compared with the control group.
      Vascular endothelial growth factor expression was significantly decreased in the
      candesartan, CDDP, and candesartan-CDDP groups compared with the control group.
      The apoptotic index was significantly increased in the CDDP and candesartan-CDDP
      groups compared with the control and candesartan groups. CONCLUSIONS: It is quite
      likely that candesartan and CDDP suppressed tumor growth by inhibiting
      angiogenesis and inducing apoptosis, respectively. Furthermore, combined
      treatment with candesartan enhanced CDDP-induced cytotoxicity by further
      suppressing angiogenesis. These results suggest that candesartan could be a
      candidate for innovational therapy of bladder cancer.

PMID- 19167033
TI  - Effect of antiepileptic agent, levetiracetam, on urodynamic parameters and
      neurogenic bladder overactivity in chronically paraplegic rats.
AB  - OBJECTIVES: To investigate the effects of different levetiracetam (LEV) doses on
      urodynamic parameters in an animal model of neurogenic detrusor overactivity
      (NDO). METHODS: A total of 54 female rats were studied. Of the 54 rats, 6 served
      as normal controls, and 48 underwent T10 spinal cord transection (SCT). Of the
      latter 48 rats, 12 were paraplegic controls, and the remaining 36 rats were
      divided into 3 equal subgroups that received LEV by way of a subcutaneous osmotic
      minipump at a dose of 17, 54, and 108 mg/kg daily, respectively. The paraplegic
      control and treatment groups were further subdivided (n = 6), and cystometry was
      performed at 3 and 4 weeks after SCT, respectively. RESULTS: All paraplegic
      controls developed NDO, with spontaneous contractions. At 3 and 4 weeks after
      SCT, the mean frequency of the contractions was 1.6 +/- 0.3/min and 1.7 +/-
      0.2/min. The contraction amplitude and bladder capacity were not significantly
      different. After 1 week of LEV treatment, these urodynamic parameters improved
      significantly in a dose-dependent manner, and the changes were more striking at 2
      weeks. At a LEV dosage of 17, 54, and 108 mg/kg, respectively, the NDO frequency
      increased from 1.7 +/- 0.3 to 0.7 +/- 0.2 contractions/min (P = .01), 0.48 +/-
      0.16 contractions/min (P = .009), and 0.5 +/- 0.17 contractions/min (P = .01).
      The bladder capacity increased from 0.51 +/- 0.1 mL to 1.5 +/- 0.2 mL (P =
      .0001), 2.5 +/- 1.7 mL (P = .006), and 2.6 +/- 0.3 mL (P = .0003), and the
      micturition pressure improved from 105.8 +/- 6.9 to 73.8 +/- 6.8 cm H(2)O (P =
      .01), 58.6 +/- 8.9 cm H(2)O (P = .006), and 49.7 +/- 8.9 cm H(2)O (P = .002).
      CONCLUSIONS: The results of our study have shown that LEV is an effective
      treatment of NDO after SCT in rats. It might prove to be a novel, alternative
      therapeutic approach to NDO. The follow-up of these experimental results with a
      clinical trial is warranted.

PMID- 19167034
TI  - Effect of socioeconomic factors on long-term mortality in men with clinically
      localized prostate cancer.
AB  - OBJECTIVES: To examine the effect of socioeconomic factors on survival in black
      and white patients with local or regional prostate cancer. METHODS: All cases (n
      = 2046) of clinically localized prostate cancer diagnosed from 1990 to 2000 at
      the Henry Ford Health System and the Henry Ford Medical Group, equal access
      health centers, were included. Data on the stage, grade, age at diagnosis,
      socioeconomic status, treatment given, comorbidities, and vital statistics were
      gathered from the Henry Ford Medical Group tumor registry and computerized
      databases, pathologic reports, patient charts, Surveillance, Epidemiology, and
      End Results database, and the national death registry. The endpoints were the
      overall and cancer-specific survival. Survival was calculated using Cox
      proportional hazards regression models. RESULTS: Of the 2046 cases, 1243 were
      white and 803 were black. Black patients were more likely to have lower incomes,
      a greater baseline prostate-specific antigen level, and greater comorbidities.
      They were also more likely to undergo radiotherapy and less likely to undergo
      radical prostatectomy. Univariate analysis, with white race as the baseline
      hazard, showed that black patients had significantly increased cancer-specific
      (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.01-2.13) and overall (HR
      1.29, 95% CI 1.09-1.53) mortality. However, adjusting for insurance status and
      income on multivariate analysis revealed no significant differences in cancer
      specific (HR 1.04, 95% CI 0.66-1.64) and overall (HR 0.96, 95% CI 0.78-1.18)
      survival. CONCLUSIONS: In this cohort, socioeconomic factors were sufficient to
      explain the disparity in survival between white and black patients. Survival
      differences disappeared after adjusting for income status on multivariate
      analysis.

PMID- 19167035
TI  - Effect of postcystectomy infectious complications on cost, length of stay, and
      mortality.
AB  - OBJECTIVES: To analyze the effect of infectious complications after cystectomy
      using the Nationwide Inpatient Samples of the Healthcare Cost and Utilization
      Project. The economic and clinical effects of infectious complications after
      radical cystectomy have not been analyzed. METHODS: All 6686 patients undergoing
      radical cystectomy for bladder cancer were identified from the nationwide
      inpatient samples from 2000 to 2004. Septicemia, bacterial infections, and
      mycosis were categorized using the Clinical Classification Software. We then
      analyzed the effect of septicemia on in-hospital mortality, length of stay, and
      total hospital charges. RESULTS: Of the 6686 patients, 241 (3.6%) were diagnosed
      with septicemia after cystectomy. The overall, in-hospital mortality rate was
      16.67% (n = 33). Septicemia was a significant predictor of in-hospital mortality
      (P < .001). The mean hospital charge for patients with septicemia was nearly 3
      times the amount for the control patients ($161,277 vs $58,560, P < .001). The
      length of stay was 3 times longer for patients with septicemia than for controls
      (29 vs 10 days, P < .001). The hospital charges for bacterial infections (n =
      161) and mycotic infections (n = 154) were significantly greater than their
      matched control population ($107,734 and vs $60,716 and $102,541 vs $67,016,
      respectively, P < .001 for both). CONCLUSIONS: The development of septicemia
      after cystectomy predicts for patient mortality. Septicemia, bacterial
      infections, and mycotic infections contribute to large increases in the length of
      stay and total hospital charges.

PMID- 19167036
TI  - Comparative analysis of surgical margins between radical retropubic prostatectomy
      and RALP: are patients sacrificed during initiation of robotics program?
AB  - OBJECTIVES: To compare the incidence of positive surgical margins obtained with
      robotic-assisted laparoscopic prostatectomy (RALP), during the initiation of a
      robotics program, with that from a similarly matched cohort of open radical
      retropubic prostatectomy (RRP) cases as performed by a single surgeon. METHODS:
      From December 2005 to March 2008, 63 patients underwent RRP and another 50
      underwent RALP by a single urologist. The records were retrospectively reviewed,
      and 50 RRP patients were selected from the RRP group whose records were similar
      to the records of the 50 patients who had undergone RALP. We compared the
      incidence of positive surgical margins and the location of positive margins among
      the 2 groups. Additional variables evaluated included the preoperative prostate
      specific antigen level, preoperative Gleason score, clinical stage, postoperative
      Gleason score, tumor volume, and pathologic stage. RESULTS: The positive margin
      rate for the RRP group was 36% compared with 22% for the RALP group (P = .007).
      The incidence of positive margins for pathologic Stage pT2c disease in the RALP
      group was 22.8% compared with 42.8% in the RRP group, a statistically significant
      difference (P = .006). Fewer positive margins were found in the RALP Gleason
      score 7 group than in the RRP group, 29% vs 60%, again a statistically
      significant difference (P = .003). CONCLUSIONS: We present our series comparing a
      single urologist's positive margin rates during the learning curve of a robotics
      program with his experience of a similarly matched cohort of RRP patients. A
      statistically significant lower positive margin rate can be achieved in RALP
      patients even during the learning period.

PMID- 19167037
TI  - Coronal computed tomography of penile implant.
AB  - Computed tomography with multiplanar reconstruction is fast becoming routine in
      clinical practice. This method is not only able to solve complex imaging issues,
      but at times brings back fond childhood memories.

PMID- 19167038
TI  - Ventral plication for repair of pediatric dorsal penile curvature.
AB  - OBJECTIVES: To present the results of ventral plication for the repair of dorsal
      curvature. METHODS: A total of 33 patients (mean age 38 months, range 7 months to
      15 years) with a dorsal curvature of >30 degrees degrees underwent ventral
      plication. A subcoronal incision was performed, followed by degloving of the skin
      to the penile base. The point of maximal curvature was noted and marked during an
      erection test. Two polypropylene 5-0 plication sutures were placed in the tunica
      albuginea of both corporeal bodies, just lateral and adjacent to the corpus
      spongiosum. Proper alignment and a straight penis were confirmed with a repeat
      erection test. The skin incision was closed with absorbable sutures. Surgical
      success was determined by parental and physician satisfaction with the final
      outcome during follow-up. RESULTS: No immediate or late complications (mean
      follow-up 25 months, range 3-65) developed. A straight penis was achieved in 28
      of 33 patients (85%). Four patients with residual curvature did not require a
      second procedure, and the fifth patient successfully underwent reoperation using
      the same technique. CONCLUSIONS: The results of our study have shown that ventral
      plication is a simple and efficient technique for the repair of dorsal penile
      curvature.

PMID- 19167039
TI  - Role of oxidative stress in pathogenesis of varicocele and infertility.
AB  - This review summarizes the published literature about the role of oxidative
      stress in the pathophysiology of varicocele and the beneficial effects of
      varicocele repair on oxidative stress. Literature survey was performed using the
      Medline, EMBASE, BIOSIS, and Cochrane databases between 1993 and 2008 that were
      relevant to oxidative stress and varicocele. Varicocele treatment can reduce
      reactive oxygen species levels and improve sperm parameters and pregnancy rates,
      although it is still controversial with Assisted Reproductive Techniques
      outcomes. We conclude that spermatozoal dysfunction in varicocele patients could
      be multifactorial, and oxidative stress-induced injury appears to be one of the
      main causes.

PMID- 19167040
TI  - Role of cellular oxalate in oxalate clearance of patients with calcium oxalate
      monohydrate stone formation and normal controls.
AB  - OBJECTIVES: To examine the cellular, plasma, and urinary oxalate and erythrocyte
      oxalate flux in patients with calcium oxalate monohydrate (COM) stone formation
      vs normal controls. Pathologic oxalate clearance in humans is mostly integrated
      in calcium oxalate stone formation. An underlying cause of deficient oxalate
      clearance could be defective transmembrane oxalate transport, which, in many
      tissues, is regulated by an anion exchanger (SLC26). METHODS: We studied 2
      groups: 40 normal controls and 41 patients with COM stone formation. Red blood
      cells were divided for cellular oxalate measurement and for resuspension in a
      buffered solution (pH 7.40); 0.1 mmol/L oxalate was added. The supernatant was
      measured for oxalate immediately and 1 hour after incubation. The plasma and
      urinary oxalate were analyzed in parallel. RESULTS: The mean cellular oxalate
      concentrations were significantly greater in the normal controls (5.25 +/- 0.47
      micromol/L) than in those with COM stone formation (2.36 +/- 0.28 micromol/L; P <
      .01). The mean urinary oxalate concentrations were significantly greater in those
      with COM stone formation (0.31 +/- 0.02 mmol/L) than in the controls (0.24 +/-
      0.02 mmol/L; P < .01). The cellular oxalate concentrations correlated
      significantly with the plasma (r = 0.49-0.63; P < .01) and urinary oxalate (r = 
      0.29-0.41; P < .03) concentrations in both groups. The plasma oxalate
      concentrations correlated significantly with the urinary oxalate concentrations
      (r = -0.30; P < .03) in the controls and with the erythrocyte oxalate flux (r =
      0.25; P < .05) in those with COM stone formation. CONCLUSIONS: Our data implicate
      the presence of a cellular oxalate buffer to stabilize plasma and urinary oxalate
      concentrations in normal controls.

PMID- 19167041
TI  - Downregulation of lectin-like oxidized low-density lipoprotein receptor-1 after
      ischemic preconditioning in ischemia-reperfused rat kidneys.
AB  - OBJECTIVES: To investigate the effects of ischemic preconditioning on renal
      injury in ischemia-reperfused kidneys. METHODS: A total of 60 rats undergoing
      right nephrectomy were randomized to the following groups: group 1, sham-operated
      control; group 2, 45 minutes ischemia alone; group 3, 5 minutes of ischemia
      followed by 5 minutes of reperfusion before 45 minutes of ischemia. The left
      kidneys of 5 rats were removed immediately and 6, 12, and 24 hours after the
      surgical procedure. The concentrations of nitric oxide (NO) metabolites were
      measured using the Griess method, and the expression levels of lectin-like
      oxidized low-density lipoprotein receptor-1 (LOX-1) and clusterin were determined
      by real-time reverse transcriptase-polymerase chain reaction. The degree of renal
      injury was evaluated using the terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end assay. RESULTS: No significant changes were
      found in the serum or renal concentrations of the NO metabolites or the
      expression levels of renal LOX-1 and clusterin in group 1. The serum and renal
      concentrations of the NO metabolites in group 3 were significantly greater than
      those in group 2 at 24 and 12 hours after reperfusion, respectively. The LOX-1
      expression in group 3 was significantly downregulated compared with that in group
      2 at 6 and 12 hours after reperfusion, and the clusterin expression level in
      group 3 was significantly greater than that in group 2 at 6 and 12 hours after
      reperfusion. The degree of renal injury in group 2 was significantly more severe
      than in groups 1 and 3. CONCLUSIONS: Pretreatment of ischemic preconditioning
      resulted in the induction of protective effects on ischemia/reperfusion-induced
      injury through the inhibition of apoptosis, in which enhanced production of NO
      and downregulation of LOX-1 induced by ischemic preconditioning might be
      involved.

PMID- 19167042
TI  - Temporary balloon occlusion of inferior vena cava in resection of renal tumor
      with vena cava thrombus extension.
AB  - OBJECTIVES: To investigate a novel and effective method to occlude the inferior
      vena cava (IVC) during surgical management of a renal tumor with a tumor thrombus
      extension into the IVC. METHODS: We retrospectively reviewed the records of 10
      patients with renal cell carcinoma or renal angiomyolipoma with tumor thrombus
      extending into the IVC who had undergone surgical intervention at our institute
      from May 2005 to May 2006. The balloon occlusion of the IVC was performed during
      surgery to decrease the risk of pulmonary embolism. RESULTS: One patient could
      not tolerate the test occlusion of the IVC and the procedure was converted to IVC
      right atrium bypass. The remaining 9 patients successfully underwent nephrectomy
      and thrombectomy with the help of temporary balloon obstruction of the IVC
      without perioperative mortality or morbidity. The blood pressure and circulatory
      status were stably maintained during occlusion of the IVC. CONCLUSIONS: Temporary
      balloon occlusion of the IVC is a simple and reliable technique that decreases
      the risk of pulmonary embolism and facilitates the resection of renal tumor with
      levels II and III IVC thrombus.

PMID- 19167043
TI  - Gastric diverticulum mimicking cystic lesion in left adrenal gland.
AB  - Adrenal pseudotumors can have many origins. We report the case of a gastric
      subcardial diverticulum misdiagnosed as a left adrenal cystic lesion on magnetic
      resonance imaging. A retrospective study of a previous computed tomography scan
      detected a previously unnoticed gastric diverticulum. The embryology, clinical
      aspects, and explanation of the misdiagnosis are exposed.

PMID- 19167044
TI  - Treatment of metastatic renal cell cancer with sunitinib during chronic
      hemodialysis.
AB  - OBJECTIVES: To report on 2 cases of metastatic renal cell cancer treated with
      sunitinib during chronic hemodialysis. METHODS: Two patients who were receiving
      chronic hemodialysis were treated with escalating doses of sunitinib with close
      clinical and laboratory surveillance. RESULTS: The treatment toxicities were
      tolerable even after dose escalation. The first patient had a complete response
      after 5 treatment cycles and the second patient had stable disease after 13
      treatment cycles. CONCLUSIONS: Sunitinib treatment is feasible and effective
      against metastatic renal cell cancer with the patient receiving chronic
      hemodialysis. Patients with terminal renal failure can be offered sunitinib
      treatment with close clinical and laboratory monitoring.

PMID- 19167045
TI  - Relationship between cysteinyl-leukotriene-1 receptor and human transitional cell
      carcinoma in bladder.
AB  - OBJECTIVES: To investigate the leukotriene (LT) D(4) (LTD(4)) receptor (cysteinyl
      LT(1) receptor [CysLT(1)R]) expression in transitional cell carcinoma (TCC) of
      the bladder, as well as the effects of the CysLT(1)R antagonist on cell
      proliferation in TCC cell lines. The metabolism of arachidonic acid by either
      cyclooxygenase or lipoxygenase is thought to play an important role in
      carcinogenesis. LTD(4) is a pro-inflammatory mediator derived from arachidonic
      acid through various enzymatic steps, and 5-lipoxygenase is an important factor
      in generating LTD(4). METHODS: CysLT(1)R expression in TCC tissue and normal
      bladder tissue was examined. CysLT(1)R expression was detected using
      immunohistochemistry. The effects of the CysLT(1)R antagonist on TCC cell growth
      were examined by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyltetrazolium
      bromide assay and reverse transcriptase-polymerase chain reaction. Flow cytometry
      was used to determine whether the CysLT(1)R antagonist induced apoptosis.
      RESULTS: Initially, only slight CysLT(1)R expression was detected in normal
      bladder tissues and marked CysLT(1)R expression was detected in the TCC tissues.
      CysLT(1)R expression was greater in high-grade cancer than in low-grade cancer.
      Furthermore, CysLT(1)R expression was also greater in advanced-stage cancer than
      in early-stage cancer. Finally, the CysLT(1)R antagonist caused marked inhibition
      of TCC cells by inducing early apoptosis. CONCLUSIONS: CysLT(1)R was induced in
      TCC. The results suggest that the CysLT(1)R antagonist might mediate potent
      antiproliferative effects on TCC cells. Thus, the target of the CysLT(1)R is
      potentially a new therapy in the treatment of TCC.

PMID- 19167046
TI  - Suprapubic mass in patient with neurogenic bladder due to spinal cord injury
      managed with indwelling suprapubic tube.

PMID- 19167047
TI  - Primary bilateral adrenal non-Hodgkin's lymphoma associated with normal adrenal
      function.
AB  - Primary bilateral adrenal non-Hodgkin's lymphoma is rare. Adrenal insufficiency
      or adrenal failure as a result of tumor destruction is the main
      pathophysiological change of most cases. Normal adrenal function despite bulky
      bilateral adrenal masses is extremely rare. We present a case of primary
      bilateral adrenal non-Hodgkin's lymphoma associated with normal adrenal function.
      Positron emission tomography-computed tomography is helpful to the diagnosis.

PMID- 19167048
TI  - Sacral neuromodulation in children with dysfunctional elimination syndrome:
      description of incisionless first stage and second stage without fluoroscopy.
AB  - OBJECTIVES: To detail a percutaneous technique of sacral nerve neuromodulation
      (SN) that eliminates the first-stage incisions and the need for second-stage
      fluoroscopy. Our group has previously described the results of SN in children
      with medically refractory dysfunctional elimination syndrome. The drawbacks to SN
      include the use of fluoroscopy and the need to reopen recent skin incisions
      during the second stage. This results in increased radiation exposure, poor
      cosmesis, and possible wound infection. METHODS: The incisionless first stage
      consisted of percutaneously tunneling the temporary external appliance to the
      contralateral axillary line at the buttock after localization of the S3 nerve
      root and placement of a quadripolar tined lead under fluoroscopic guidance. A
      subcutaneous bolus of methylene blue marked the lead connector site, obviating
      the need for later fluoroscopic localization to place the implantable pulse
      generator at the second stage. RESULTS: A total of 27 children with refractory
      dysfunctional elimination syndrome underwent SN using the InterStim device. Of
      the 27 patients, 19 underwent our modified technique. The operative time for our
      modified tunneling and placement technique was < or = 2 minutes. The mean
      hospital stay was 0.6 day, with no patient requiring postoperative intravenous
      narcotics. At a mean follow-up of 35.9 months, no wound infections had occurred
      in the incisionless cohort compared with 1 postoperative wound infection
      requiring device explantation in the conventional lead placement group.
      CONCLUSIONS: The incisionless technique of SN device implantation is technically
      simple, quick to perform, and results in decreased radiation exposure, excellent
      pain control, and improved cosmesis without compromising the outcomes.

PMID- 19167049
TI  - Comparison of D&C and office endometrial biopsy accuracy in patients with FIGO
      grade 1 endometrial adenocarcinoma.
AB  - OBJECTIVE: To compare the accuracy of D&C vs office endometrial biopsy in
      predicting final post-hysterectomy FIGO grade in patients diagnosed with a
      preoperative FIGO grade 1 endometrial adenocarcinoma. METHODS: We reviewed 1423
      consecutive cases of endometrial cancer treated at our institution between 1/1/93
      and 5/31/06 and identified cases with an unequivocal preoperative endometrial
      biopsy demonstrating FIGO grade 1 endometrial adenocarcinoma. All cases were
      pathologically confirmed and underwent surgical therapy at our institution. FIGO
      grade and histology diagnosed in the hysterectomy specimen were noted. The
      findings in the hysterectomy specimen were then compared between those patients
      who had a preoperative D&C vs an office endometrial sampling. Chi-square and
      Fisher-exact test were used as appropriate. RESULTS: We identified 490 cases with
      a preoperative FIGO grade 1 endometrial adenocarcinoma. In 482 cases, FIGO grade
      was determined to be greater in 71 (14.7%) cases; in the final hysterectomy
      specimen, 66 (13.7%) were found to be grade 2 and 5 (1%) were found to be grades
      2-3/3. Serous or clear cell histology was diagnosed in 6 (1.2%) additional cases.
      D&C was performed in 187 (38.6%) cases and office endometrial sampling in 298
      (61.4%); in 5 cases the method used was not discernible. The final post
      hysterectomy FIGO grade was higher in 16/187 (8.7%) cases diagnosed by D&C
      compared to 52/298 (17.4%) diagnosed by office endometrial sampling (P=0.007).
      CONCLUSIONS: Preoperative FIGO grade 1 diagnosis correlates with final grade
      diagnosis in 85% of cases. While D&C more accurately reflects final FIGO grade, a
      higher grade will be found in 8.7% of the cases at the time of hysterectomy.

PMID- 19167050
TI  - Sentinel node of endometrial cancer after hysteroscopic injection.

PMID- 19167051
TI  - Importin 8 is a gene silencing factor that targets argonaute proteins to distinct
      mRNAs.
AB  - Small regulatory RNAs including small interfering RNAs (siRNAs) and microRNAs
      (miRNAs) guide Argonaute (Ago) proteins to specific target RNAs leading to mRNA
      destabilization or translational repression. Here, we report the identification
      of Importin 8 (Imp8) as a component of miRNA-guided regulatory pathways. We show
      that Imp8 interacts with Ago proteins and localizes to cytoplasmic processing
      bodies (P bodies), structures involved in RNA metabolism. Furthermore, we detect
      Ago2 in the nucleus of HeLa cells, and knockdown of Imp8 reduces the nuclear Ago2
      pool. Using immunoprecipitations of Ago2-associated mRNAs followed by microarray
      analysis, we further demonstrate that Imp8 is required for the recruitment of Ago
      protein complexes to a large set of Ago2-associated target mRNAs, allowing for
      efficient and specific gene silencing. Therefore, we provide evidence that Imp8
      is required for cytoplasmic miRNA-guided gene silencing and affects nuclear
      localization of Ago proteins.

PMID- 19167052
TI  - Polarization-sensitive optical coherence tomographic imaging of artificial
      demineralization on exposed surfaces of tooth roots.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the potential
      of polarization-sensitive optical coherence tomography (PS-OCT) to non
      destructively measure the depth and severity of artificial demineralization on
      exposed root surfaces and measure the degree of inhibition by topical fluoride.
      Although PS-OCT imaging studies have demonstrated the utility of PS-OCT for
      imaging carious lesions on enamel and dentin surfaces the influence of the
      cementum layer that is present on intact root surfaces has not been investigated.
      MATERIALS AND METHODS: In this study, extracted human tooth roots were
      partitioned into three sections with one partition treated with topical fluoride,
      one partition protected from demineralization with acid resistant varnish, and
      one partition exposed to a demineralization solution, producing artificial
      lesions approximately 200-mum deep in root dentin. The lesion depth, remaining
      cementum thickness and the integrated reflectivity for lesion areas were measured
      with PS-OCT. These measurements were also compared with more established methods
      of measuring demineralization, namely transverse microradiography (TMR) and
      polarized light microscopy (PLM). RESULTS: PS-OCT was able to measure a
      significant increase in the reflectivity between lesion areas and sound root
      surfaces. In contrast to dentin, the cementum layer manifests minimal
      reflectivity in the PS-OCT images allowing non-destructive measurement of the
      remaining cementum thickness. The reflectivity of the cementum layer did not
      increase significantly after substantial demineralization, however it did
      manifest considerable shrinkage in a fashion similar to dentin and that shrinkage
      could be measured with OCT. SIGNIFICANCE: This study demonstrates that PS-OCT can
      be used to measure demineralization non-destructively on root surfaces and assess
      inhibition of demineralization by anti-caries agents.

PMID- 19167053
TI  - Trade in health-related services.
AB  - The supervision of a domestic health system in the context of the trade
      environment in the 21st century needs a sophisticated understanding of how trade
      in health services affects, and will affect, a country's health system and
      policy. This notion places a premium on people engaged in the health sector
      understanding the importance of a comprehensive outlook on trade in health
      services. However, establishment of systematic comparative data for amounts of
      trade in health services is difficult to achieve, and most trade negotiations
      occur in isolation from health professionals. These difficulties compromise the
      ability of a health system to not just minimise the risks presented by trade in
      health services, but also to maximise the opportunities. We consider these issues
      by presenting the latest trends and developments in the worldwide delivery of
      health-care services, using the classification provided by the World Trade
      Organization for the General Agreement on Trade in Services. This classification
      covers four modes of service delivery: cross-border supply of services;
      consumption of services abroad; foreign direct investment, typically to establish
      a new hospital, clinic, or diagnostic facility; and the movement of health
      professionals. For every delivery mode we discuss the present magnitude and
      pattern of trade, main contributors to this trade, and key issues arising.

PMID- 19167054
TI  - Trade, TRIPS, and pharmaceuticals.
AB  - The World Trade Organization's Agreement on Trade-Related Aspects of Intellectual
      Property Rights (TRIPS) set global minimum standards for the protection of
      intellectual property, substantially increasing and expanding intellectual
      property rights, and generated clear gains for the pharmaceutical industry and
      the developed world. The question of whether TRIPS generates gains for developing
      countries, in the form of increased exports, is addressed in this paper through
      consideration of the importance of pharmaceuticals in health-care trade,
      outlining the essential requirements, implications, and issues related to TRIPS,
      and TRIPS-plus, in which increased restrictions are imposed as part of bilateral
      free-trade agreements. TRIPS has not generated substantial gains for developing
      countries, but has further increased pharmaceutical trade in developed countries.
      The unequal trade between developed and developing countries (ie, exporting and
      importing high-value patented drugs, respectively) raises the issue of access to
      medicines, which is exacerbated by TRIPS-plus provisions, although many countries
      have not even enacted provision for TRIPS flexibilities. Therefore this paper
      focuses on options that are available to the health community for negotiation to
      their advantage under TRIPS, and within the presence of TRIPS-plus.

PMID- 19167055
TI  - Trade agreements and health in developing countries.

PMID- 19167056
TI  - Trade and health: an agenda for action.
AB  - The processes of contemporary globalisation are creating ever-closer ties between
      individuals and populations across different countries. The health of a
      population, and the systems in place to deliver health care, are affected
      increasingly by factors beyond the population and health system. The Lancet's
      Series on trade and health has provided an overview of these links between
      international trade, trade liberalisation, and health, and raised the key issues
      that face the health community. In this final paper in the Series, we call for a
      substantial and sustained effort by those within the health profession to engage
      with issues of trade, to strengthen institutional capacity in this area, and to
      place health higher on the agenda of trade negotiations. The rapid rise of trade
      agreements and treaties, as well as trade that occurs beyond these institutional
      boundaries, means that further action is required by a range of actors, including
      WHO, the World Bank, the World Trade Organization (WTO), regional agencies,
      foundations, national governments, civil society, non-governmental organisations,
      and academics. The stewardship of a domestic health system in the 21st century
      requires a sophisticated understanding of how trade affects, and will affect, a
      country's health system and policy, to optimise opportunities to benefit health
      and health care while minimising the risks posed though the assertion of health
      goals in trade policy. To acheive this will place a premium on all those engaged
      in health to understand the importance of trade and to engage with their
      counterparts involved in trade and trade policy. We hope that this Series has
      prompted the reader to become involved in these efforts.

PMID- 19167057
TI  - Trade and health: the need for a political economic analysis.

PMID- 19167058
TI  - Trade and social determinants of health.
AB  - The effects of trade and trade liberalisation on the social determinants of
      health are not well known. Here, we outline a conceptual framework of links
      between trade liberalisation and health outcomes, and review existing evidence
      for these by focusing on four key factors: income, inequality, economic
      insecurity, and unhealthy diets. Even though trade liberalisation seems to have
      positive effects on economic growth, it is not sufficient to boost growth. In
      several countries, trade reforms have not translated into enhanced economic
      expansion because complementary policies are needed. Trade liberalisation and
      openness are associated with greater wage inequality and raised economic
      insecurity. Trade liberalisation has facilitated availability of highly
      processed, calorie-rich, nutrient-poor food in developing countries, but further
      research is needed to better understand the effects of trade on unhealthy diets.
      Policymakers and health professionals need to be aware that the global economy
      affects the health of populations and understand how risks associated with trade
      liberalisation can be mitigated.

PMID- 19167059
TI  - Health before profits? Learning from Thailand's experience.

PMID- 19167060
TI  - Bridging the divide: global governance of trade and health.
AB  - The main institutions responsible for governing international trade and health
      the World Trade Organization (WTO), which replaced the General Agreement on
      Tariffs and Trade (GATT) in 1995, and WHO-were established after World War 2. For
      many decades the two institutions operated in isolation, with little cooperation
      between them. The growth and expansion of world trade over the past half century
      amid economic globalisation, and the increased importance of health issues to the
      functioning of a more interconnected world, brings the two domains closer
      together on a broad range of issues. Foremost is the capacity of each to govern
      their respective domains, and their ability to cooperate in tackling issues that
      lie at the intersection of trade and health. This paper discusses how the
      governance of these two areas relate to one another, and how well existing
      institutions work together.

PMID- 19167061
TI  - Managing the pursuit of health and wealth: the key challenges.
AB  - This article forms part of a six-part Series on trade and health, and sets the
      stage for this Series by analysing key aspects of the relationship between trade
      and health. The Series takes stock of this relation and provides timely analysis
      of the key challenges facing efforts to achieve an appropriate balance between
      trade and health across a diverse range of issues. This introductory article
      reviews how trade and health have risen and expanded on global policy agendas in
      the past decade in unprecedented ways, describes how trade and health issues are
      respectively governed in international relations, examines the ongoing search for
      policy coherence between the two policy spheres, and highlights the topics of the
      remaining articles in the Series.

PMID- 19167062
TI  - Trade and health: time for the health sector to get involved.

PMID- 19167063
TI  - 17beta-Estradiol overcomes human myeloma RPMI8226 cell suppression of growth, ALP
      activity, and mineralization in rat osteoblasts and improves RANKL/OPG balance in
      vitro.
AB  - Multiple myeloma (MM) is a plasma cell malignancy characterized by a high
      capacity to induce osteolytic bone lesions. MM patients with osteolytic bone
      lesions have lower numbers of osteoblasts and decreased bone formation, which
      plays a critical role in the bone-destructive process. Although the mechanism of
      estrogen action on bone cells and myeloma cells has been widely investigated,
      estrogen action on bone cells in MM is unknown. In this study, the effects of the
      gonadal hormone 17beta-estradiol on cell growth, alkaline phosphatase (ALP)
      activity, mineralization capacity, and RANKL/OPG ratios in primary rat
      osteoblasts cultured with MM cell conditioned medium (CM) or co-cultured with
      RPMI8226 cells were investigated. Treatments of 10(-2) to 10 nM 17beta-estradiol
      reversed inhibition of proliferation and ALP activity of osteoblasts by myeloma
      cells in a dose-dependent manner, and 10(-2) to 1 nM 17beta-estradiol reversed
      inhibition of the mineralization capacity of osteoblasts by myeloma cells. In co
      culture experiments with primary rat osteoblasts and myeloma cells, treatments of
      10(-2) to 10 nM 17beta-estradiol down-regulated transcription and secretion of
      RANKL and up-regulated transcription and secretion of OPG in the osteoblasts,
      reversing the effects of co-cultured myeloma cells. These findings suggest that
      17beta-estradiol may temper the inhibitory effects of myeloma cells on
      osteoblasts and improve RANKL/OPG balance, providing a new agent for treatment of
      bone disease in myeloma.

PMID- 19167064
TI  - Is it possible to discontinue imatinib mesylate therapy in Chronic Myeloid
      Leukemia patients with undetectable BCR/ABL? A case report and a review of the
      literature.
AB  - Imatinib mesylate (IM) therapy leads to a complete cytogenetic response (CCyR) in
      75-90% of Chronic Myeloid Leukemia (CML) patients in chronic phase, but only a
      small percentage of patients achieve complete molecular response (CMR). Very
      little is known about IM discontinuation. We report the case of a 20-years-old
      male patient in chronic phase CML who maintained undetectable BCR/ABL mRNA
      levels, despite IM discontinuation over a period of 15 months after achieving
      CMR. Our patient reached CCyR and CMR after 3 and 6 months of IM treatment,
      respectively. We also reviewed the published literature concerning cases of IM
      discontinuation.

PMID- 19167065
TI  - Information needs of adult patients 50 or older with newly diagnosed acute
      myeloid leukemia.
AB  - When faced with a life-threatening illness such as acute myeloid leukemia (AML),
      patients may feel overwhelmed with making treatment decisions. We recruited 31
      consecutive English-speaking patients aged > or = 50 with newly diagnosed AML. We
      explored patient information needs, decision-making roles, and perceptions about
      prognosis. Most patients felt that they had enough information about the
      diagnosis and treatment options and that the doctor spent the right amount of
      time with them. The majority of patients preferred a passive or collaborative
      decision-making role. Almost half the patients did not know their estimated 6
      month prognosis, and 17% felt it was 90% or better.

PMID- 19167066
TI  - The contribution of childhood emotional abuse to teen dating violence among child
      protective services-involved youth.
AB  - OBJECTIVE: For child protective services (CPS) youth who may have experienced
      more than one form of maltreatment, the unique contribution of emotional abuse
      may be over-looked when other forms are more salient and more clearly outside of
      accepted social norms for parenting. This study considers the unique predictive
      value of childhood emotional abuse for understanding adolescent post-traumatic
      stress disorder (PTSD) symptomatology and dating violence. Further, PTSD
      symptomatology is assessed as an explanatory bridge in the emotional abuse-teen
      dating violence link. METHODS: A random sample of 402 youth from the active
      caseload of a large urban CPS catchment area participated as part of a larger
      longitudinal study on adolescent health behaviors. Mid-adolescent youth across
      types of CPS status were targeted. CPS youth reported on lifetime maltreatment
      experiences, PTSD symptomatology, and past year dating experiences, using
      published scales. RESULTS: Over 85% of CPS youth had begun dating. For dating
      youth, some level of dating violence was common: over half of females (63-67%)
      and nearly half of males (44-49%). Taking into account other forms of
      maltreatment, emotional abuse emerged as a significant predictor of both PTSD
      symptomatology and dating violence among males and females. PTSD symptomatology
      was a significant mediator of the male emotional abuse-perpetration and the
      female emotional/physical abuse-victimization links, indicating a gendered
      patterning to findings. CONCLUSIONS: These results indicate that: (1) CPS youth
      are a high priority group for dating violence and PTSD-linked intervention; and
      (2) CPS youth continue to experience the unique negative impact of childhood
      emotional abuse in their adolescent adjustment. All CPS children should be
      evaluated for emotional abuse incurred, and appropriate intervention attention be
      given as to how it specifically impacts on the child's approach to relating to
      themselves and to others. PRACTICE IMPLICATIONS: The present study directs
      practice implications in regards to: (1) the problem of teen dating violence, (2)
      the salience of childhood emotional abuse; and (3) the importance of targeting
      PTSD symptomatolgy among CPS youth. A substantial number of CPS youth report
      early engagement in violent romantic relationships and require support towards
      attaining the non-coercive relationship experiences of their non-CPS-involved age
      mates. The topic of dating, healthy dating relationships, and dating violence may
      need to be part of the regular casework, with a view towards supporting youths'
      conceptualization of and skill set for healthy, close relationships. Further,
      this knowledge needs to be translated to foster parents and group home staff.
      With regard to the impact of childhood emotional abuse, CPS workers need to be
      sensitive to its potential for long-term, unique impact impairing relationship
      development. Emotional abuse is (a) unique among genders (i.e., for females, it
      clusters with physical abuse) and (b) uniquely predictive of PTSD symptoms and
      dating violence. Finally, as is consistent with theory and biopsychosocial
      evidence, PTSD symptomatology is a key causal candidate for understanding
      maltreatment-related impairment. Attention to targeting PTSD symptoms may be
      preventative for dating violence; attention to targeting emotional abuse
      experiences may be preventative for PTSD symptoms. CPS youth are an important
      population to involve in research, as their inclusion adds to the evidence-base
      to achieve evidence-informed practice and policy within child welfare.

PMID- 19167067
TI  - Childhood emotional maltreatment and later psychological distress among college
      students: the mediating role of maladaptive schemas.
AB  - OBJECTIVE: Theoretically, exposure to experiences of emotional abuse (EA) and
      emotional neglect (EN) in childhood may threaten the security of attachment
      relationships and result in maladaptive models of self and self-in-relation to
      others. The purpose of this study was to explore the extent to which EA and EN
      treatment by parents contributed uniquely to young adult maladaptive long-term
      outcome with respect to symptoms of anxiety, depression, and dissociation. The
      extent to which the relationships between EA and EN and later symptoms were
      mediated by specific internalized maladaptive interpersonal schemas was also
      explored. METHODS: Questionnaires completed by 301 college men and women (52%
      female) assessed perceptions of experiences of childhood abuse and neglect,
      exposure to parental alcoholism, current symptoms of psychological distress, and
      endorsement of maladaptive interpersonal schemas. RESULTS: Hierarchical
      regression analyses revealed that perceptions of childhood EA and EN each
      continued to exert an influence on later symptoms after controlling for gender,
      income, parental alcoholism, and other child abuse experiences. Both EA and EN
      were associated with later symptoms of anxiety and depression and were mediated
      by schemas of vulnerability to harm, shame, and self-sacrifice. Only EN was
      related to later symptoms of dissociation; this relationship was mediated by the
      schemas of shame and vulnerability to harm. CONCLUSION: The findings are
      discussed from an attachment perspective, focusing on how early interactions with
      parents contribute to the development of internal working models of self and self
      in-relation to others that influence later cognitive schemas and psychological
      adjustment. PRACTICE IMPLICATIONS: Although emotional abuse and emotional neglect
      are the least studied of all forms of child maltreatment, they may be the most
      prevalent. The current findings suggest that how college students have evaluated
      and internalized these experiences may be even more important than the events
      themselves in determining the extent to which these experiences exert a long-term
      impact. For this reason, early intervention might be particularly important in
      helping to modify internal working models of the self as worthless, others as
      abusive, or the world as threatening and dangerous as a result of past abuse
      experiences. This study underscores the need for counselors to actively elicit
      and explore experiences of emotional abuse and neglect in clients, in addition to
      inquiring about other abuse experiences and types of family dysfunction. The
      results of this study also support existing data suggesting that internalized
      representational models of self and others are a key mechanism underlying the
      relationship between emotional maltreatment and later psychopathology. Young's
      schema questionnaire proved to be quite sensitive in detecting specific
      maladaptive schemas that mediated later difficulties with depression, anxiety,
      and dissociation. Targeting these negative schemas in therapy may help to
      ameliorate such symptoms. The therapeutic relationship provides a particularly
      effective context for developing more positive models of self and others, as well
      as providing a context to explore core relationship themes across different
      relationship contexts (e.g., intimate partner, parent, friend, and work
      relationships). In particular, if the assessment of the client reveals that
      dissociative symptoms are present, counselors can acknowledge the adaptive
      function that this strategy once served, while also addressing potential
      limitations to over-reliance on this coping strategy.

PMID- 19167068
TI  - Taking stock: childhood emotional maltreatment and developmental psychopathology.

PMID- 19167069
TI  - The relation of emotional maltreatment to early adolescent competence:
      developmental processes in a prospective study.
AB  - OBJECTIVES: This investigation examined developmental pathways between childhood
      emotional maltreatment and adaptational outcomes in early adolescence. This study
      utilized a developmental psychopathology perspective in adopting a
      multidimensional approach to the assessment of different forms of emotional
      maltreatment and later adjustment outcomes. Specifically, emotional abuse (i.e.,
      verbal criticism, hostility) and emotional neglect (i.e., psychological
      unavailability) were compared using a process-level analytic approach to examine
      if and how different forms of emotional maltreatment would contribute to
      adolescent adjustment via aggression and social withdrawal in middle childhood.
      METHODS: The current study sample is drawn from a longitudinal, prospective study
      of a high-risk community sample (N=196), incorporating a multi-method and multi
      informant design. Multiple mediator models were tested via bootstrapping
      regression techniques. RESULTS: Bivariate correlations revealed that both
      emotional neglect and emotional abuse were associated with increased aggression
      and social withdrawal in middle childhood, and lower ratings of socioemotional
      competence in early adolescence. However, the mediational model, which controlled
      for child gender and concurrent physical and sexual maltreatment, was only
      significant for the contribution of emotional abuse to lower adolescent
      competence via social withdrawal in middle childhood. Post hoc analyses revealed
      that this association was only significant for boys. CONCLUSIONS: While social
      withdrawal in middle childhood significantly explained the observed relation
      between emotional abuse and decreased competence in adolescence, this process did
      not emerge as salient in understanding the relation between emotional neglect and
      adolescent adaptation. Furthermore, these developmental processes appeared to
      vary by gender. The results are in need of replication and extension to other
      outcome domains, but represent an important contribution to the empirical study
      of specific forms of emotional maltreatment. PRACTICE IMPLICATIONS: Emotional
      maltreatment is generally overlooked and unrecognized as compared to physical or
      sexual forms of maltreatment. This study adds to the accumulating empirical
      evidence that the effects of emotional maltreatment are disabling, enduring, and
      should be carefully assessed by clinicians. Furthermore, this assessment should
      specify the particular form of emotional maltreatment that has occurred, as the
      results of the study indicate that developmental processes and adjustment
      outcomes may vary according the type of emotional maltreatment (i.e., emotional
      abuse, emotional neglect) that is experienced. Finally, clinicians must recognize
      that a single maltreatment type may vary in its impact on subsequent adjustment,
      as significant gender differences emerged in the current study that point to the
      role of individual differences that warrant further investigation.

PMID- 19167070
TI  - Parental physical and psychological aggression: psychological symptoms in young
      adults.
AB  - OBJECTIVE: The purpose of the present study was to evaluate the relationship
      between various levels of parent-child physical violence and psychological
      symptoms reported by college students, while controlling for demographic
      variables, severity and frequency of violence, and co-occurrence of parental
      psychological aggression. METHOD: Participants included 298 college students
      ranging in age from 18 to 27 years. Participants completed a demographic
      information form, the Brief Symptom Inventory (BSI), and the Parent-Child
      Conflict Tactics Scale (CTSPC). RESULTS: Results of analysis of variance and
      multivariate analysis of variance indicated that individuals in the child
      physical abuse group obtained higher BSI scores compared to individuals in the
      corporal punishment and no violence groups. Few differences were observed between
      mild and severe corporal punishment groups. Multiple regression analyses
      indicated that when frequency of corporal punishment, child physical abuse, and
      psychological aggression, along with demographic variables, were considered
      simultaneously, psychological aggression was the most unique predictor of BSI
      scores. CONCLUSIONS: The findings suggest that severe forms of physical violence
      were associated with long-term psychological symptoms. When demographic variables
      and the frequency of several parent aggression variables were considered
      simultaneously, however, psychological aggression was most predictive of
      psychological outcome. These findings suggest that messages communicated to a
      child via psychological aggression may be more important in contributing to
      psychological outcome than the actual occurrence of physical violence toward the
      child. PRACTICE IMPLICATIONS: The current study supports the premise that severe
      physical aggression experienced in childhood is associated with serious
      psychological consequences in adulthood. In contrast, individuals who experienced
      less severe forms of parent-child violence, such as corporal aggression,
      exhibited similar symptom levels to those reporting no parent-child violence.
      When severe physical aggression, corporal aggression, and psychological
      aggression were considered simultaneously, however, psychological aggression
      emerged as the most unique predictor of psychological outcome. Researchers and
      clinicians who work with adults reporting childhood histories of severe parent
      child violence should be aware of the importance of parent-child psychological
      aggression in contributing to psychological outcome.

PMID- 19167071
TI  - Factors influencing enrollment: a case study from Birth to Twenty, the 1990 birth
      cohort in Soweto-Johannesburg.
AB  - Longitudinal studies offer significant advantages in rendering data commensurate
      with the complexity of human development. However, incomplete enrollment and
      attrition over time can introduce bias. Furthermore, there is a scarcity of
      evaluative information on cohorts in developing countries. This paper documents
      various strategies adopted to minimize loss to follow up and describes a
      retrospective analysis of a small group of families who were missed during
      initial enrollment and through several subsequent rounds of data collection of
      the Birth to Twenty (BT20) birth cohort in Soweto-Johannesburg, South Africa that
      began in 1990. A purposive case study approach was used, and 10 of the 119
      families missed at enrollment were interviewed to investigate why these families
      were not enrolled into the study. The findings demonstrate that high mobility,
      both within urban areas and between urban and rural areas, are a major challenge
      for longitudinal studies in densely populated urban areas. In addition,
      enrollment was also affected by individuals changing their names, largely
      motivated to facilitate access to employment under Apartheid, as well as varying
      motivations for participating in research. Longitudinal studies in the developing
      country context must be mindful of the political, social and economic climate
      that influences enrollment and ongoing cohort maintenance.

PMID- 19167072
TI  - Evaluation of the Integrated Services Pilot Program from Western Australia.
AB  - Independent evaluation of refugee-focused programs in developed nations is
      increasingly a mandatory requirement of funding bodies and government agencies.
      This paper presents an evaluation of the Integrated Services Centre (ISC) Pilot
      Project that was conducted in Australia in 2007 and early 2008. The purpose of
      the ISC program was to provide integrated support to humanitarian refugees in
      settlement, physical health, mental health and employment. The Pilot Project was
      based in two primary schools in Perth, Western Australia. The evaluation utilized
      a flexible qualitative 'engaged' methodology and included interviews, focus
      groups and telephone interviews with the key stakeholders, project staff and a
      small number of refugee families. The strength of the qualitative methodology
      (including data that is narrative rich) is that it highlights issues as perceived
      by each stakeholder and provides insights into the daily work by ISC staff that
      helped to uncover unintended outcomes. Despite the fact that the ISC evaluation
      was supposed to be a 'before and after' design, the researchers acknowledge a
      common weakness in many evaluations (including the ISC) that when baseline data
      is required, evaluators are recruited after the project has begun. This issue is
      discussed in the paper. It is critical that independent evaluators are able to
      begin collecting baseline data as soon as programs are launched, if not before.

PMID- 19167073
TI  - Assessing noxious effects of dietary exposure to methylmercury, PCBs and Se
      coexisting in environmentally contaminated rice in male mice.
AB  - Polychlorinated biphenyls and methylmercury are two of the most ubiquitous
      environmental contaminants in Guizhou province. Rice is eaten with almost every
      meal and provides more calories than any single food in Guizhou province. The
      estimated tolerable daily intake of total mercury, MeHg, Se and PCBs from Guizhou
      contaminated rice by Chinese people showed that MeHg and/or PCBs exceeded the
      corresponding limits. The aim of this study was to characterize the effects of
      exposure to environmental contaminated rice on neurobehavioral development and
      neurobiological disruptions in mice. Animals were treated from postnatal day
      (PND) 22 to 91. At PND 26-91 days of age, mice were tested for neurobehavioural
      development and neurochemical level changes. We showed that dietary exposure to
      environmentally contaminated rice gave rise to different changes in antioxidants.
      Reduced superoxide dismutase (SOD) activity and excess increased nitric oxide
      (NO) indicated aggravation of oxidative status after long-term dietary intake of
      Hg and PCBs. Neurobehavioral derangement in the central nervous system and
      significant delay in the Morris water maze test response on PND 91 are correlated
      with the increased of c-fos/c-jun expression levels in the cerebral cortex. These
      results suggest that MeHg neurotoxicity might be a greater hazard than that
      associated with PCB, but PCB may augment the neurobehavioral deficits caused by
      increased levels of mercury exposure. The simultaneous intake of selenium might
      have a protective effect on Hg accumulation in the body, and vitamin C might
      protect mice against the toxic effects of PCBs. However, the protective role of
      Se and vitamin C is very limited for multiple-agent pollution. Immediately early
      genes in the brain response to contaminated rice might be dependent on
      interaction among NO, NO synthase (NOS), SOD and reduced glutathione (GSH). We
      should be alert to mental health problems in human beings when any kind of Hg-
      and PCB-polluted food is consumed.

PMID- 19167074
TI  - Common buzzards (Buteo buteo) bio-indicators of heavy metals pollution in Sicily
      (Italy).
AB  - The aim of this study was to evaluate the accumulation of toxic (As, Cd and Pb)
      and essential (Cu, Mn and Zn) metals in samples (feathers, liver, kidney, lung,
      intestine and muscle) of common buzzards (Buteo buteo) from Sicily, used as bio
      indicators for monitoring environmental metals pollution. All samples of buzzards
      were collected at the "Recovery Center of Wild Fauna" of Palermo, through the
      Zooprophilactic Institute. The quantitative determinations of metals were carried
      out using an atomic absorbtion spectrophotometer (AAS). The results obtained
      showed the presence of metals in all samples analyzed. For toxic metals the
      highest levels of Pb and As were found in liver and those of Cd in kidney; for
      essential metals Zn levels were higher than Cu and Mn in all tissues analyzed.
      Significant differences are observed in metal levels between female and male and
      juvenile and adult bird samples. Highest metal levels found in liver, kidney and
      muscle can be considered indicative of chronic exposure to metals while the
      presence of metals in feathers can be consequential to storing and elimination
      processes. The results obtained suggest that common buzzards (Buteo buteo) may be
      very useful as bio-indicators for monitoring environmental pollution.

PMID- 19167075
TI  - Study of environmental burden of lead in children using teeth as bioindicator.
AB  - The south region of Sao Paulo city hosts the Guarapiranga dam, responsible for
      water supply to 25% of the city population. Their surroundings have been subject
      to intense and irregular occupation by people from very low socioeconomics
      classes. Measurements undertaken on sediment and particulate materials in the dam
      revealed concentrations of lead, copper, zinc and cadmium above internationally
      accepted limits. Epidemiological and toxicological studies undertaken by the
      World Health Organization in individuals exhibiting lead concentrations in blood,
      near or below the maximum recommended (10 microg dl(-1)), surprisingly revealed
      that toxic effects are more intense in individuals belonging to low
      socioeconomics classes. Motivated by these facts, we aimed at the investigation
      of chronic incorporation of lead, as well as the use of our BIOKINETICS code,
      which is based on an accepted ICRP biokinetics model for lead, in order to
      extrapolate the results from teeth to other organs. The focus of our data taking
      was children from poor families, living in a small, restrict and allegedly
      contaminated area in Sao Paulo city. Thus, a total of 74 human teeth were
      collected. The average concentration of lead in teeth of children 5 to 10 years
      old was determined by means of a high-resolution inductively coupled plasma mass
      spectrometer (ICP-MS). For standardization of the measurements, an animal bone
      certified material (H-Animal Bone), from the International Atomic Energy Agency,
      was analyzed. The amount of lead in children living in the surroundings of the
      dam, was approximately 40% higher than those from the control region, and the
      average lead concentration was equal to 1.3 microg g(-1) approximately. Grouping
      the results in terms of gender, tooth type and condition, it was concluded that a
      carious molar of boys is a much more efficient contamination pathway for lead,
      resulting in concentrations 70% higher than in the control region. We also
      inferred the average concentrations of lead in other organs of these children, by
      making use of our BIOKINETIC code.

PMID- 19167076
TI  - Beta2-adrenergic receptor regulate Toll-like receptor 4-induced late-phase NF
      kappaB activation.
AB  - Stimulation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) triggers
      myeloid differentiation factor 88 (MyD88)-dependent early-phase NF-kappaB
      activation and Toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta
      (TRIF)-dependent late-phase NF-kappaB activation. In a previous study, we have
      shown that beta(2)-adrenergic receptor (beta(2)AR) functions as a negative
      regulator of NF-kappaB activation through beta-arrestin 2 in the macrophage cell
      line RAW264 and that down-regulation of beta(2)AR expression in response to LPS
      is essential for NF-kappaB activation and expression of its target gene,
      inducible nitric oxide synthase (NOS II). Here, we demonstrate that beta(2)AR
      plays an important role in TRIF-dependent late-phase NF-kappaB activation. LPS
      stimulated down-regulation was induced in MyD88-knockdown cells, but not in TRIF
      knockdown cells, suggesting that beta(2)AR expression was down-regulated by the
      TRIF-dependent pathway. On the other hand, depletion of beta(2)AR or beta
      arrestin 2 expression by siRNA decreased cytoplasmic IkappaB alpha and abrogated
      late-phase IkappaB alpha degradation and NF-kappaB activation in response to LPS.
      Inducible nitric oxide synthase (NOS II) expression was increased continuously
      during 24 h of LPS stimulation in control cells, but decreased in beta(2)AR or
      beta-arrestin 2-knockdown cells after 6 h of LPS stimulation. These findings
      suggest that beta(2)AR functions not only as a negative regulator of NF-kappaB
      activation, but also as a stabilizing factor of the NF-kappaB/IkappaB alpha
      complex through cytoplasmic beta-arrestin 2, and that TRIF-dependent down
      regulation of beta(2)AR expression increases the level of cytoplasmic NF
      kappaB/IkappaB alpha complex free from beta-arrestin 2, leading to continuous
      late-phase NF-kappaB activation.

PMID- 19167077
TI  - Contact lens wear is associated with decrease of meibomian glands.
AB  - PURPOSE: Approximately 30% to 50% of contact lens (CL) wearers report dry eye
      symptoms. Meibomian gland dysfunction has been recognized as a possible cause of
      CL-related dry eye. This study investigated the influence of CL wear on the
      meibomian glands using a newly developed meibographic technique. DESIGN: Cross
      sectional observational case series. PARTICIPANTS: Contact lens wearers (n=121;
      47 men, 74 women; mean age+/-standard deviation, 31.8+/-8.0 years) and healthy
      volunteers (n=137; 71 men, 66 women; mean age+/-standard deviation, 31.4+/-15.1
      years). METHODS: The following tests were performed: slit-lamp examinations of
      the eyelids, corneal and conjunctival staining using fluorescein, measurement of
      the tear film breakup time, evaluation of the meibomian glands using noncontact
      meibography, and measurement of tear production using the Schirmer I test.
      Partial or complete loss of the meibomian glands was scored for each eyelid using
      4 grades (meiboscores): grade 0 (no loss of meibomian glands) through grade 3
      (the area characterized by gland dropout was more than 66% of the total area
      containing the meibomian glands). The meiboscores for the upper and lower eyelids
      were summed for each subject. MAIN OUTCOME MEASURES: Score of meibomian gland
      changes (meiboscore), tear film breakup time, and Schirmer test value. RESULTS:
      The meiboscore was significantly higher (P<0.0001) in CL wearers (mean, 1.72; 95%
      confidence interval, 1.47-1.96) than in the control group (mean, 0.96; 95%
      confidence interval, 0.73-1.19). The average meiboscore of CL wearers was similar
      to that of a 60- to 69-year-old age group from the normal population. A
      significant positive correlation was observed between the duration of CL wear and
      the meiboscore. CONCLUSIONS: Contact lens wear is associated with a decrease in
      the number of functional meibomian glands. This decrease is proportional to the
      duration of CL wear.

PMID- 19167078
TI  - SCORE Study report 1: baseline associations between central retinal thickness and
      visual acuity in patients with retinal vein occlusion.
AB  - OBJECTIVE: To investigate the relationship between baseline center point retinal
      thickness measured by optical coherence tomography (OCT) and best-corrected
      visual acuity in eyes with macular edema associated with retinal vein occlusion
      and to investigate other factors associated with baseline visual acuity letter
      score. DESIGN: The Standard Care versus COrticosteroid for REtinal Vein Occlusion
      (SCORE) Study includes 2 multicenter, randomized clinical trials: one evaluating
      participants with central retinal vein occlusion (CRVO) and the other evaluating
      participants with branch retinal vein occlusion (BRVO). PARTICIPANTS: After
      omitting 17 participants with missing or unreliable OCT measurements, analyses
      proceeded with 665 enrolled SCORE Study participants (665 eyes), including 262
      with CRVO and 403 with BRVO. METHODS: At baseline, center point thickness was
      measured by OCT (Stratus OCT 3 [n=663] and OCT2 [n=2]; Carl Zeiss Meditech,
      Dublin, CA), and visual acuity was measured by the electronic Early Treatment
      Diabetic Retinopathy Study (E-ETDRS) methodology. MAIN OUTCOME MEASURES: Center
      point thickness and best-corrected E-ETDRS visual acuity letter score. RESULTS:
      The correlation coefficient for the association between baseline OCT-measured
      center point thickness and best-corrected E-ETDRS visual acuity letter score is 
      0.27 (95% confidence limit: -0.38 to -0.16) for participants in the CRVO trial
      and -0.28 (95% confidence limit: -0.37 to -0.19) in the BRVO trial. Regression
      modeling estimated the following decrease in baseline visual acuity letter score
      for every 100-microm increase in OCT-measured center point thickness: 1.7 letters
      (P=0.0007) for CRVO and 1.9 letters (P<0.0001) for BRVO. On the basis of
      multivariate regression models, baseline factors significantly associated
      (P<0.05, after adjusting for multiple testing) with baseline visual acuity letter
      score include age and duration of macular edema for CRVO participants and center
      point thickness and presence of cystoid spaces for BRVO participants.
      CONCLUSIONS: The correlation between OCT-measured center point thickness and
      visual acuity letter score is modest. OCT-measured center point thickness
      represents a useful tool for the detection and monitoring of macular edema in
      retinal vein occlusion, but it cannot reliably substitute for visual acuity
      measurements.

PMID- 19167079
TI  - The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: the twenty-five
      year incidence of macular edema in persons with type 1 diabetes.
AB  - OBJECTIVE: To examine the 25-year cumulative incidence of macular edema (ME) and
      its relation to various risk factors. DESIGN: Population-based study.
      PARTICIPANTS: A total of 955 insulin-taking persons living in an 11-county area
      in southern Wisconsin with type 1 diabetes diagnosed before age 30 years who
      participated in baseline examinations (1980-1982) and at least 1 of 4 follow-up
      (4-, 10-, 14-, and 25-year) examinations (n=891) or died before the first follow
      up examination (n=64). METHODS: Stereoscopic color fundus photographs were graded
      using the modified Airlie House classification and the Early Treatment Diabetic
      Retinopathy Study retinopathy severity scheme. Competing risk of death was
      included in statistical models. MAIN OUTCOME MEASURES: Incidence of ME and
      clinically significant ME (CSME). RESULTS: The 25-year cumulative incidence was
      29% for ME and 17% for CSME. Annualized incidences of ME were 2.3%, 2.1%, 2.3%,
      and 0.9% in the first, second, third, and fourth follow-up periods of the study,
      respectively. In univariate analyses, the incidence of ME was associated with
      male sex, more severe diabetic retinopathy, higher glycosylated hemoglobin,
      proteinuria, higher systolic and diastolic blood pressure, and more pack-years of
      smoking. Multivariate analyses showed that the incidence of ME was related to
      higher baseline glycosylated hemoglobin (hazard ratio [HR] per 1% 1.17; 95%
      confidence interval [CI], 1.10-1.25; P<0.001) and higher systolic blood pressure
      (HR per 10 mmHg 1.15; 95% CI, 1.04-1.26; P=0.004) and marginally to proteinuria
      (HR 1.43; 95% CI, 0.99-2.08; P=0.06). CONCLUSIONS: These data show that
      relatively high 25-year cumulative rates of incidence of ME were related to
      glycemia and blood pressure. The lower risk of incident ME in the last period of
      the study may reflect recent improvement in care.

PMID- 19167080
TI  - Diagnostic accuracy of pattern electroretinogram optimized for glaucoma
      detection.
AB  - PURPOSE: To assess the ability of the new pattern electroretinogram optimized for
      glaucoma detection (PERGLA) paradigm to discriminate between healthy individuals
      and individuals with glaucomatous optic neuropathy (GON). DESIGN: Cross-sectional
      study. PARTICIPANTS: One hundred forty-two eyes of 71 participants (42 healthy
      and 29 with GON in at least 1 eye) enrolled in the University of California, San
      Diego, Diagnostic Innovations in Glaucoma Study were studied. Healthy individuals
      were those recruited as healthy with healthy-appearing optic disc by examination
      and masked stereoscopic optic disc photograph evaluation. Glaucomatous optic
      neuropathy was defined based on stereophotograph evaluation. METHODS: The PERGLA
      (Glaid Elettronica, Pisa, Italy) recordings were obtained within 6 months of
      standard automated perimetry (SAP) testing. Dependent variables were PERGLA
      amplitude, phase, amplitude asymmetry, phase asymmetry, and SAP pattern standard
      deviation (PSD) and mean deviation (MD). MAIN OUTCOME MEASURES: Diagnostic
      accuracy (sensitivity and specificity) of the PERGLA normative database for
      classifying healthy and glaucomatous individuals was determined. In addition,
      performance (areas under receiver operating characteristic curves [AUCs]) of
      PERGLA amplitude and phase for classifying healthy (n=84) and GON (n=50) eyes was
      determined. Results from both analyses were compared with those from SAP.
      RESULTS: Sensitivity and specificity of the PERGLA normative database were 0.76
      and 0.59, respectively, compared with 0.83 and 0.77 for SAP. The AUCs for PERGLA
      amplitude and phase were 0.75 and 0.50 (chance performance), respectively. The
      AUCs for SAP PSD and MD were 0.83 and 0.78, respectively. CONCLUSIONS: Pattern
      electroretinograms recorded using the PERGLA paradigm can discriminate between
      healthy and glaucoma eyes, although this technique performed no better than SAP
      at this task. Low specificity of the PERGLA normative database suggests that the
      distribution of recordings included in the database is not ideal.

PMID- 19167081
TI  - Atropine for the treatment of childhood myopia: effect on myopia progression
      after cessation of atropine.
AB  - PURPOSE: The aim of this study was to assess the effect on myopia progression
      after cessation of topical atropine treatment. DESIGN: Parallel-group, placebo
      controlled, randomized, double-masked study. PARTICIPANTS: Four hundred children
      aged 6 to 12 years with refractive error of spherical equivalent -1.00 to -6.00
      diopters (D) and astigmatism of -1.50 D or less. INTERVENTION: No intervention
      was administered. Subjects were followed up for 12 months after stopping
      treatment, which consisted of either 1% atropine or vehicle eyedrops once nightly
      for 2 years. Only 1 eye of each subject was chosen through randomization for
      treatment. MAIN OUTCOME MEASURES: The main efficacy outcome measures were change
      in spherical equivalent refraction as measured by cycloplegic autorefraction and
      change in ocular axial length as measured by ultrasonography. RESULTS: After
      cessation of atropine drops, the mean progression in the atropine-treated group
      was -1.14+/-0.80 D over 1 year, whereas the progression in placebo-treated eyes
      was -0.38+/-0.39 D (P<0.0001). However, after 3 years of participation in the
      trial (with 2 years on atropine treatment), eyes randomized to atropine have less
      severe myopia than other eyes. Spherical equivalent was -4.29+/-1.67 D in the
      atropine-treated eyes compared with -5.22+/-1.38 D in the placebo-treated eyes
      (P<0.0001). Spherical equivalents in atropine-untreated and placebo-untreated
      eyes were -5.00+/-1.62 D and -5.28+/-1.43 D, respectively. Over the 3 years, the
      increase in axial length of the atropine-treated eyes was 0.29+/-0.37 mm compared
      with 0.52+/-0.45 mm in the placebo-treated eyes (P<0.0001). After cessation of
      atropine, the amplitude of accommodation and near visual acuity returned to
      pretreatment levels. CONCLUSIONS: After stopping treatment, eyes treated with
      atropine demonstrated higher rates of myopia progression compared with eyes
      treated with placebo. However, the absolute myopia progression after 3 years was
      significantly lower in the atropine group compared with placebo.

PMID- 19167083
TI  - Congenital monocular elevation deficiency.
AB  - OBJECTIVE: The pathophysiology of monocular elevation deficiency is poorly
      understood. The goal of this study was to determine the appearance of the
      extraocular muscles and the oculomotor nerve. DESIGN: Observational case series.
      PARTICIPANTS: Six patients with monocular elevation deficiency. METHODS:
      Ophthalmologic examination and thin-sectioned magnetic resonance imaging (MRI) at
      the brainstem level as well as across the orbit in 6 patients were performed.
      MAIN OUTCOME MEASURES: Ocular alignment and movement, extraocular muscles, and
      the oculomotor nerve on MRI. RESULTS: One out of 6 patients with monocular
      elevation deficiency showed focal thickening of the inferior rectus muscle near
      the orbital apex. The 5 remaining patients showed normal extraocular muscles and
      the oculomotor nerves on MRI. CONCLUSIONS: Focal thickening of the inferior
      rectus muscle may partially explain the cause of restricted gaze. In addition,
      the finding of normal oculomotor nerves might support an underlying deficit in
      the unilateral center for upgaze as the etiology of monocular elevation
      deficiency.

PMID- 19167082
TI  - Photoreceptor layer thinning over drusen in eyes with age-related macular
      degeneration imaged in vivo with spectral-domain optical coherence tomography.
AB  - PURPOSE: Detect changes in the neurosensory retina using spectral-domain optical
      coherence tomography (SD OCT) imaging over drusen in age-related macular
      degeneration (AMD). Quantitative imaging biomarkers may aid in defining risk of
      disease progression. DESIGN: Cross-sectional, case-control study evaluating SD
      OCT testing in AMD. PARTICIPANTS AND CONTROLS: Seventeen eyes of 12 subjects with
      nonneovascular AMD and drusen and 17 eyes of 10 age-matched control subjects.
      METHODS: Spectral-domain OCT imaging across the fovea in the study eye with
      multiple 10- to 12-mm scans of 1000 A scans each. MAIN OUTCOME MEASURES: In
      summed SD OCT scans, the height of individual retinal layers either over drusen
      or at corresponding locations in the control eye and qualitative changes in
      retinal layers over drusen. Secondary measures included photoreceptor layer (PRL)
      area, inner retinal area, and retinal pigment epithelium (RPE)/drusen area.
      RESULTS: The PRL was thinned over 97% of drusen, average PRL thickness was
      reduced by 27.5% over drusen compared with over a similar location in controls,
      and the finding of a difference was valid and significant (P=0.004).
      Photoreceptor outer segments were absent over at least 1 druse in 47% of eyes.
      Despite thinning of the PRL, inner retinal thickness remained unchanged. We
      observed 2 types of hyperreflective abnormalities in the neurosensory retina over
      drusen. Distinct hyperreflective speckled patterns occurred over drusen in 41% of
      AMD eyes and never in control eyes. A prominent hyperreflective haze was present
      in the photoreceptor nuclear layer over drusen in 67% of AMD eyes and more subtly
      in the photoreceptor nuclear layer in 18% of control eyes (no drusen).
      CONCLUSIONS: With SD OCT as used in this study, we can easily detect and measure
      changes in PRL over drusen. Decreased PRL thickness over drusen suggests a
      degenerative process, with cell loss leading to decreased visual function. The
      hyperreflective foci overlying drusen are likely to represent progression of
      disease RPE cell migration into the retina and possible photoreceptor
      degeneration or glial scar formation. A longitudinal study using SD OCT to
      examine and measure the neurosensory retina over drusen will resolve the timeline
      of degenerative changes relative to druse formation.

PMID- 19167084
TI  - Risk factors for intraoperative complications in resident-performed
      phacoemulsification surgery.
AB  - PURPOSE: To determine the risk factors for intraoperative complications in
      resident-performed phacoemulsification surgery and the effect of complications on
      postoperative visual acuity. DESIGN: Retrospective case series. PARTICIPANTS: A
      total of 320 consecutive eyes of predominantly male (96.6%) and elderly patients
      (mean age +/-1 standard deviation = 73.1+/-10.0 years) undergoing
      phacoemulsification surgery by ophthalmology residents at a Veterans
      Administration Hospital between January 2006 and 2007. There were no exclusion
      criteria for type of cataract undergoing phacoemulsification surgery. METHODS:
      Data were collected by review of patients' electronic medical records. Collected
      data included the patient demographics, ocular comorbidities, cataract features,
      resident, resident experience, attending, right or left eye, anesthesia type,
      wound type, phacoemulsification technique, preoperative and postoperative visual
      acuities, and presence of any intraoperative complication. Multivariate models
      were constructed to determine potential risk factors for intraoperative
      complications. MAIN OUTCOME MEASURES: Major intraoperative complication rate,
      risk factors for major intraoperative complications, and best-corrected
      postoperative visual acuity. RESULTS: The major intraoperative complication rate
      was 4.7%, which included 3.1% of cases with vitreous loss. The strongest
      association with a major complication was the presence of a case identified as
      challenging preoperatively, which had an odds ratio of 6.0 (95% confidence
      interval [CI], 1.5-24.1, P=0.01). The challenging features most strongly
      associated with major complications were mature 4+ nuclear sclerotic cataracts
      and zonular pathology (antecedent trauma and pseudoexfoliation), which had odds
      ratios of 18.9 (95% CI, 3.1-117, P=0.002) and 26.2 (95% CI, 4.3-159, P=0.003),
      respectively. A major complication decreased the likelihood of achieving 20/40 or
      better visual acuity within 90 days of surgery (95% of uncomplicated eyes vs. 71%
      of complicated eyes; P=0.009). CONCLUSIONS: Residents performing
      phacoemulsification surgery achieved a low overall rate of major complications.
      However, specific features of cataracts, such as mature nuclei and zonular
      pathology, carried increased intraoperative risk. Anticipating risk may help to
      decrease surgical complications further and to counsel patients appropriately.

PMID- 19167085
TI  - Extremely low penetrance of Leber's hereditary optic neuropathy in 8 Han Chinese
      families carrying the ND4 G11778A mutation.
AB  - PURPOSE: To investigate the role of mitochondrial haplotypes in the development
      of Leber's hereditary optic neuropathy (LHON) associated with the ND4 G11778A
      mutation in Chinese families. DESIGN: Eight Han Chinese families with maternally
      transmitted LHON were studied using clinical, genetic, and molecular evaluations.
      PARTICIPANTS: One hundred sixty-seven subjects from 8 Chinese families with a
      wide age range and severity of visual impairment. METHODS: All subjects underwent
      the clinical and genetic evaluation, as well as molecular analysis of
      mitochondrial DNA (mtDNA). MAIN OUTCOME MEASURES: The ophthalmologic examinations
      included visual acuity, visual field examination, visual evoked potentials, and
      fundus photography. Mitochondrial DNA analysis included the polymerase chain
      reaction amplification of the entire mtDNA and subsequent sequence determination.
      RESULTS: Eight families exhibited extremely low penetrance of visual impairment,
      with the average of 13%. In particular, 14 (12 males and 2 females) of 119
      matrilineal relatives in these families exhibited the variable severity and age
      at onset in visual dysfunction. The average age of onset of vision loss was 17
      years. Molecular analysis of mtDNA identified the homoplasimic ND4 G11778A
      mutation and distinct sets of variants belonging to the Asian haplogroups M8a2,
      D4g2, B4a1c, B5b, N9a1, D4b2b, C, and M7b1. However, there was an absence of
      secondary LHON-associated mtDNA mutations in these 8 Chinese families.
      CONCLUSIONS: The extremely low penetrance of vision loss in these 8 Chinese
      pedigrees strongly indicates that the G11778A mutation was itself insufficient to
      produce a clinical phenotype. The absence of secondary LHON mtDNA mutations
      suggest that these mtDNA haplogroup-specific variants may not play an important
      role in the phenotypic expression of the G11778A mutation in those Chinese
      families with very low penentrace of vision loss. However, nuclear backgrounds
      and environmental factors seem to be modifying factors for the phenotypic
      manifestation of the G11778A mutation in these Chinese families.

PMID- 19167086
TI  - The association of cutaneous and iris nevi with uveal melanoma: a meta-analysis.
AB  - PURPOSE: To study the relationship between cutaneous and iris nevi with uveal
      melanoma. DESIGN: Meta-analysis. METHODS: Three researchers independently
      searched the literature using Medline from 1966 to August 2007 (with both Ovid
      and PubMed), EMBASE, MD Consult, and the Web of Science. All bibliographies were
      searched, and an attempt to contact all primary authors was made to find further
      unpublished studies. MAIN OUTCOME MEASURES: Risk factor data were extracted into
      4 a priori groups: (1) atypical cutaneous nevi, (2) common cutaneous nevi, (3)
      cutaneous freckles, and (4) iris nevi. RESULTS: Meta-analysis of 4 studies (850
      cases) examining atypical cutaneous nevi yielded a summary odds ratio (OR) of
      2.82 (95% confidence interval [CI], 1.10-7.26; P=0.032). Common cutaneous nevi
      were reported in 4 studies (825 cases), yielding a summary OR of 1.74 (CI, 1.27
      2.39; P=0.001). Cutaneous freckles using 7 studies (2122 cases) found an OR of
      1.22 (CI, 1.03-1.45; P=0.022). Iris nevi using 4 studies (825 cases) found an OR
      of 1.53 (CI, 1.03-2.27; P=0.036). There was no evidence of publication bias for
      the aforementioned risk factors, with the exception of atypical cutaneous nevi
      (P=0.03). CONCLUSIONS: This meta-analysis supports an association between uveal
      melanoma and atypical cutaneous nevi, common cutaneous nevi, cutaneous freckles,
      and iris nevi.

PMID- 19167087
TI  - Refractive, topographic, tomographic, and aberrometric analysis of keratoconic
      eyes undergoing corneal cross-linking.
AB  - PURPOSE: To report refractive, topographic, tomographic, and aberrometric
      outcomes 12 months after corneal cross-linking (CXL) in eyes with progressive
      advanced keratoconus. DESIGN: Prospective, nonrandomized, single-center clinical
      study. PARTICIPANTS: Twenty-eight eyes undergoing CXL between April and June
      2006. INTERVENTION: Riboflavin-ultraviolet A (UVA)-induced CXL included
      instillation of 0.1% riboflavin-20% dextrane solution 30 minutes before UVA
      irradiation and every 5 minutes for an additional 30 minutes during irradiation.
      MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA), best spectacle-corrected
      visual acuity (BSCVA), sphere and cylinder refraction, topography, tomography,
      aberrometry, and endothelial cell count were evaluated at baseline and at 1, 3,
      6, and 12 months follow-up. RESULTS: Mean baseline UCVA and BSCVA were 0.17+/
      0.09 and 0.52+/-0.17, respectively; 12-month mean UCVA and BSCVA were 0.27+/-0.08
      and 0.72+/-0.16, a statistically significant difference (P<0.05). Mean spherical
      equivalent refraction showed a significant decrease of 0.41 diopters (D). Mean
      baseline simulated keratometry (SIM K) flattest and steepest meridians and SIM K
      average were 46.10, 50.37, and 48.08 D, respectively; at 12 months, 40.22, 44.21,
      and 42.01 D, respectively, were recorded, a difference that was significant for
      all 3 indices (P<0.05). Mean average pupillary power (APP) changed significantly
      from 47.50 to 41.04 D at 12 months (P<0.05) and apical keratometry (AK) from
      58.94 to 55.18 D (P<0.05). The treated eyes showed no deterioration of the Klyce
      indices at 6 months postoperatively, whereas the untreated (contralateral) eyes
      did show deterioration. For a 3-mm pupil, there was a significant reduction
      (P<0.05) in whole eye (total), corneal, higher order, and astigmatic wavefront
      aberrations. A significant difference (P<0.05) in total coma and total spherical
      aberration after CXL was also observed. Mean baseline pupil center pachymetry and
      total corneal volume decreased significantly (P<0.05) to 470.09+/-29.01 microm
      and 57.17+/-3.21 mm(3) from baseline values of 490.68+/-30.69 microm and 59.37+/
      4.36 mm(3), respectively. Endothelial cell counts did not changed significantly
      (P=0.13). CONCLUSIONS: Corneal cross-linking seems to be effective in improving
      UCVA and BSCVA in eyes with progressive keratoconus by significantly reducing
      corneal APP, AK, and corneal and total wavefront aberrations at 1 year
      postoperatively.

PMID- 19167088
TI  - Risk factors for nonulcerative contact lens complications in an ophthalmic
      accident and emergency department: a case-control study.
AB  - PURPOSE: To assess the relative risks of acute, nonulcerative complications with
      recently introduced contact lens (CL) wear modalities (compared with the
      previously most common soft lens wear schedule), and to identify any other
      associated factors. DESIGN: A 2-year prospective case-control study commencing in
      December 2003. PARTICIPANTS: Cases were 877 CL wearers attending Moorfields Eye
      Hospital with CL-related disorders other than microbial keratitis. Controls were
      1069 hospital controls who were CL wearers presenting with a disorder unrelated
      to CL wear, and 639 population-based controls who were CL wearers randomly
      selected from the Moorfields catchment area. Hospital patients completed a self
      administered questionnaire; population controls were interviewed by telephone.
      TESTING: The relative risks of developing the CL-related disorders with different
      CL types were evaluated. For the more common disorders, multivariable analysis
      was undertaken. MAIN OUTCOME MEASURES: The relative risk of developing an acute,
      nonulcerative, CL-related disorder. RESULTS: Compared with planned replacement
      soft CL, daily disposable lenses significantly reduced the risk of
      toxic/hypersensitivity (odds ratios for CL solution disorders and papillary
      conjunctivitis 0.1 and 0.5; P<0.001 and P = 0.05, respectively) and metabolic
      disorders (0.4; P=0.04), but the most commonly used brand was associated with
      increased risks of sterile keratitis (2.7x; 95% confidence interval [CI], 1.7
      4.1; P<0.001), mechanical disorders (2.2x; 95% CI, 1.5-3.2; P<0.001), and a
      tendency for patients to have lens removal difficulties (P<0.001). Silicone
      hydrogel CL wear was free from hypoxic complications but associated with an
      increased risk of sterile keratitis (2.0x; 95% CI, 1.2-3.3; P=0.005), mechanical
      disorders (1.8x; 95% CI, 1.1-2.8; P=0.015), and attendance with any nonulcerative
      complication (1.9x; 95% CI, 1.5-2.6; P<0.001) when compared with other reusable
      soft lenses. Significant additional risk factors were identified for sterile
      keratitis (overnight wear [ON], more days per week of lens wear, poor hand
      hygiene, smoking, and less CL experience) and mechanical disorders (ON and less
      CL experience). CONCLUSIONS: Neither of the 2 recently introduced CL modalities
      daily disposable and silicone hydrogel lenses-reduced the overall risk of acute
      nonulcerative disorders.

PMID- 19167089
TI  - Mechanisms of inhibition of zinc-finger transcription factors by selenium
      compounds ebselen and selenite.
AB  - The anti-inflammatory selenium compounds, ebselen (2-phenyl-1,2-benzisoselenazol
      3[2H]-one) and selenite, were found to alter the DNA binding mechanisms and
      structures of cysteine-rich zinc-finger transcription factors. As assayed by
      DNase I protection, DNA binding by TFIIIA (transcription factor IIIA,
      prototypical Cys(2)His(2) zinc finger protein), was inhibited by micromolar
      amounts of ebselen. In a gel shift assay, ebselen inhibited the Cys(2)His(2) zinc
      finger-containing DNA binding domain (DBD) of the NF-kappaB mediated
      transcription factor Sp1. Ebselen also inhibited DNA binding by the p50 subunit
      of the pro-inflammatory Cys-containing NF-kappaB transcription factor.
      Electrospray ionization mass spectrometry (ESI-MS) was utilized to elucidate
      mechanisms of chemical interaction between ebselen and a zinc-bound Cys(2)His(2)
      zinc finger polypeptide modeled after the third finger of Sp1 (Sp1-3). Exposing
      Sp1-3 to micromolar amounts of ebselen resulted in Zn(2+) release from this
      peptide and the formation of a disulfide bond by oxidation of zinc finger SH
      groups, the likely mechanism for DNA binding inhibition. Selenite was shown by
      ESI-MS to also eject zinc from Sp1-3 as well as induce disulfide bond formation
      through SH oxidation. The selenite-dependent inhibition/oxidation mechanism
      differed from that of ebselen by inducing the formation of a stable
      selenotrisulfide bond. Selenite-induced selenotrisulfide formation was dependent
      upon the structure of the Cys(2)His(2) zinc finger as alteration in the finger
      structure enhanced this reaction as well as selenite-dependent zinc release.
      Ebselen and selenite-dependent inhibition/oxidation of Cys-rich zinc finger
      proteins, with concomitant release of zinc and finger structural changes, points
      to mechanisms at the atomic and protein level for selenium-induced alterations in
      Cys-rich proteins, and possible amelioration of certain inflammatory,
      neurodegenerative, and oncogenic responses.

PMID- 19167091
TI  - Migraine: a missing link between somatic symptoms and major depressive disorder.
AB  - BACKGROUND: Research into the role of migraine in somatic symptoms of major
      depressive disorder (MDD) has long been neglected; hence, the aim of this study
      was to compare the impact of migraine and anxiety comorbidities on the somatic
      symptoms of patients with MDD. METHODS: Consecutive psychiatric outpatients with
      MDD in a medical center were enrolled. MDD and anxiety disorders were diagnosed
      using the Structured Clinical Interview for DSM-IV-TR; migraine was diagnosed
      according to the International Classification of Headache Disorders, 2nd edition.
      Four scales were administered and evaluated: the Hamilton Depression Rating
      Scale, the Depression and Somatic Symptoms Scale, the somatization subscale of
      the Symptom Checklist-90-Revised, and the Hospital Anxiety and Depression Scale.
      Multiple linear regressions were used to find the most powerful comorbidities in
      predicting somatic symptoms. RESULTS: One hundred and fifty five patients (106F,
      49M) completed the study. Subjects with migraine had higher somatic, depression
      and anxiety severities. Panic disorder was the most important factor when
      predicting somatic severity among anxiety comorbidities. Migraine (R(2)
      change=0.28 to 0.04, p<.01) was the strongest independent factor in predicting
      somatic severity, even after controlling for anxiety comorbidities and
      demographic variables. LIMITATIONS: This study used certain exclusion criteria
      when enrolling MDD outpatients, possibly introducing bias. CONCLUSIONS:
      Comorbidity with migraine was found to be associated with more somatic symptoms
      in patients with MDD, and migraine was a strong and independent predictor for the
      somatic symptoms of MDD. Future studies on the somatic symptoms of MDD should
      therefore take migraine into consideration.

PMID- 19167092
TI  - DSM-IV Major Depressive Episode in the elderly: the relationship between the
      number and the type of depressive symptoms and impairment.
AB  - BACKGROUND: There is a lack of studies that assess whether the DSM-IV criteria
      for Major Depressive Episode (MDE) that use a diagnostic threshold are valid for
      the elderly and whether each symptom of depression contributes equally to
      impairment in this group. METHOD: The Australian National Survey of Mental Health
      and Wellbeing is a population-based epidemiological survey which utilized the
      Composite International Diagnostic Instrument to diagnose MDE. Analyses were
      based on the survey respondents who endorsed either (or both) the "depressed
      mood" or "loss of interest" core MDE symptoms (60+ years, n=278; 40+ years,
      n=1020). A series of multivariate linear regression analyses were run to assess
      the relationship between the number and the type of depressive symptoms and five
      measures of impairment. RESULTS: For those aged 60+ years, a linear relationship
      alone was observed for the relationship between the number of depressive symptoms
      and each of the five measures but not all symptoms of depression were equal
      predictors of impairment; loss of energy was the most consistent predictor. When
      the regression analyses were repeated using respondents aged 40+ years,
      consistent significant interactions between age and individual symptoms of
      depression were not observed. LIMITATIONS: The dimensionality of MDE is assessed
      focusing solely on symptoms. CONCLUSIONS: Our data illustrate the apparent
      dimensional structure of MDE and the differential impact of depressive symptoms
      on impairment in an elderly sub-sample. There was little support for systematic
      age-dependent changes. Adjustments to the diagnostic criteria of MDE may not
      require age-dependent distinctions.

PMID- 19167093
TI  - Unipolar depressive disorders have a common genotype.
AB  - BACKGROUND: The purpose of this study was to estimate the contribution of
      genetic, common- and unique environmental factors in the aetiology of unipolar
      major depression (MD), and to investigate whether the unipolar depressive
      disorders; MD, atypical depression/depression NOS, dysthymia and depressive
      adjustment disorder can be viewed as various expressions of an underlying genetic
      commonality. METHODS: A sample consisting of same-sexed mono- and dizygotic twins
      was drawn from in- and outpatient hospital registers (N=303). DSM-III-R criteria
      were assessed by personal interviews. One hundred and forty-three of the probands
      fulfilled the criteria for one or another unipolar depressive disorder. Cross
      tabulations were used to compare concordance rates for MD and different
      combinations of MD and other unipolar depressive disorders. Correlations in
      liability and estimations of the heritability (h(2)) with biometrical model
      fitting were performed. RESULTS: Concordance rates were higher among MZ- than
      among DZ pairs for both MD and all the different combinations of MD and other
      unipolar depressive disorders. Cross-concordance between MD and other unipolar
      disorders was observed. In all instances, except for the situation when MD was
      considered alone, the correlations in liability among MZ pairs were more than
      twice the correlations in liability among DZ pairs. The heritability of MD was
      0.42, of MD+atypical depression 0.51, of MD+atypical depression+dysthymia 0.45
      and of MD+atypical depression+dysthymia+depressive adjustment disorder 0.46.
      LIMITATION: Probands were not sampled from the general population. Most often the
      same person interviewed both twins in a pair. CONCLUSION: Unipolar MD is
      moderately heritable without significant shared family environmental effects.
      Unipolar depressive disorders taken together are moderately heritable without any
      detectable shared family environmental effects. The tendency is towards higher
      heritability estimates for the combined groups compared to MD alone. The study
      suggests that the disorders in the unipolar depressive spectrum may be different
      manifestations of the same genetic liability.

PMID- 19167094
TI  - Use and acceptability of unsupported online computerized cognitive behavioral
      therapy for depression and associations with clinical outcome.
AB  - BACKGROUND: In a recent randomized trial, we were unable to confirm the
      previously reported high effectiveness of CCBT. Therefore, the aim of the current
      study was to have a closer look at usage and acceptability (i.e. expectancy,
      credibility, and satisfaction) of the intervention. METHODS: Depressed
      participants (N=200) were given login codes for unsupported online CCBT. A track
      and-trace system tracked which components were used. We used a 9-month follow-up
      period. RESULTS: Uptake was sufficient, but dropout was high. Many usage indices
      were positively associated with short-term depressive improvement, whereas only
      homework was related to long-term improvement. Acceptability was good and
      expectancy could predict long-term, but not short-term outcome. LIMITATIONS:
      Associations between use of CCBT and improvement are merely correlational. Our
      sample was too depressed in relation to the scope of the intervention. We relied
      on online self-report measures. Analyses were exploratory in nature. CONCLUSIONS:
      Although CCBT might be a feasible and acceptable treatment for depression, means
      to improve treatment adherence are needed for moderately to severely depressed
      individuals.

PMID- 19167095
TI  - Empathy and recognition of facial expressions of emotion in sex offenders, non
      sex offenders and normal controls.
AB  - Research conducted on empathy and emotional recognition in sex offenders is
      contradictory. The present study was aimed to clarify this issue by controlling
      for some affective and social variables (depression, anxiety, and social
      desirability) that are presumed to influence emotional and empathic measures,
      using a staged multicomponent model of empathy. Incarcerated sex offenders (child
      molesters), incarcerated non-sex offenders, and non-offender controls (matched
      for age, gender, and education level) performed a recognition task of facial
      expressions of basic emotions that varied in intensity, and completed various
      self-rating scales designed to assess distinct components of empathy (perspective
      taking, affective empathy, empathy concern, and personal distress), as well as
      depression, anxiety, and social desirability. Sex offenders were less accurate
      than the other participants in recognizing facial expressions of anger, disgust,
      surprise and fear, with problems in confusing fear with surprise, and disgust
      with anger. Affective empathy was the only component that discriminated sex
      offenders from non-sex offenders and was correlated with accuracy recognition of
      emotional expressions. Although our findings must be replicated with a larger
      number of participants, they support the view that sex offenders might have
      impairments in the decoding of some emotional cues conveyed by the conspecifics'
      face, which could have an impact on affective empathy.

PMID- 19167096
TI  - Development of cell-mediated immunity to porcine circovirus type 2 (PCV2) in
      caesarean-derived, colostrum-deprived piglets.
AB  - The interaction between porcine circovirus type 2 (PCV2) and the pig immune
      system has been suggested to be a determinant event for the pathogenesis of
      postweaning multisystemic wasting syndrome (PMWS). To gain insight into the host
      immune mechanisms developed upon PCV2 infection, early innate and adaptive immune
      responses were examined in 1-week-old, caesarean-derived, colostrum-deprived
      piglets using a subclinical infection model of PCV2 in combination with
      lipopolysaccharide (LPS) as a potential immunostimulation factor. The use of LPS
      did not show any significant effect on the course of PCV2 infection, nor did in
      the evolution of the immunological parameters evaluated. Ex vivo responses were
      detected as early as 1 day post-infection (PI) and consisted of an elevation of
      the plasmatic levels of interleukin (IL)-8 in PCV2-inoculated pigs followed by an
      increase on plasmatic IFN-alpha at day 5 PI. Regarding IL-10, only one PCV2
      inoculated pig was positive (day 7 PI); this pig was the only one in which
      viremia persisted until the end of the study. In vitro cytokine determination
      showed that, regardless of the treatment administrated to the pigs, an IL-10
      release was observed when peripheral blood mononuclear cells (PBMC) cultures were
      stimulated with PCV2. Seroconvertion to PCV2 measured by an immunoperoxidase
      monolayer assay (IPMA) occurred between 7 and 14 days PI, whereas neutralizing
      antibodies (NA) did not appear until day 29 PI. PCV2 DNA was first detected in
      serum at day 7 PI, reaching the peak of viremia between days 14 and 21 PI,
      followed by a drop in viral load that was found coincident with the appearance of
      PCV2-specific IFN-gamma-secreting cells (PCV2-IFN-gamma-SC) and NA. Results from
      the present work suggest that viral clearance might be mediated by the
      development of PCV2-IFN-gamma-SC in contribution to the PCV2-specific NA.

PMID- 19167098
TI  - Delta9-tetrahydrocannabinol and cannabidiol modulate mitogen-induced tryptophan
      degradation and neopterin formation in peripheral blood mononuclear cells in
      vitro.
AB  - Nanomolar concentrations of Delta9-tetrahydrocannabinol or cannabidiol are
      demonstrated to enhance mitogen-induced degradation of tryptophan in human
      peripheral blood mononuclear cells in dependence of CB1- or CB2-receptor
      activation. In contrast, suppression of this pathway by cannabinoids in the
      micromolar concentration range was achieved independent of cannabinoid receptor
      activation. Both cannabinoids also suppressed tryptophan degradation in
      myelomonocytic THP-1 cells stimulated with lipopolysaccharide. We conclude, that
      suppression of tryptophan degradation by cannabinoids via indoleamine-2,3
      dioxygenase, which is independent of cannabinoid receptor activation, might
      enhance the availability of tryptophan for serotonin biosynthesis and
      consequently can be important in the action of cannabinoids to improve mood
      disturbances.

PMID- 19167097
TI  - Chronic CXCL10 alters neuronal properties in rat hippocampal culture.
AB  - The chemokine CXCL10 is expressed in the central nervous system (CNS) during
      neuroinflammatory conditions. Neurons express CXCR3, the receptor for CXCL10, and
      neuronal function has been shown to be altered by acute exposure to CXCL10.
      Little is known about the effects of chronic exposure to CXCL10 on neuronal
      function. Results from our studies show that chronic exposure of cultured rat
      hippocampal neurons to CXCL10 results in altered levels of protein for GABA and
      glutamate receptors and altered synaptic network activity. These effects of
      CXCL10 may contribute to altered CNS function that occurs in some chronic
      neuroinflammatory conditions.

PMID- 19167099
TI  - Tonsillectomy vs. partial tonsillectomy for OSAS in children--10 years post
      surgery follow-up.
AB  - BACKGROUND: Today, obstructive hypertrophic tonsils are completely resected to
      remove the obstruction. Since tonsillar tissue has important protective
      characteristics, it is more logical to resect only the obstructive tonsillar
      tissue and leave remnants in the tonsillar beds, thereby presuming to preserve
      the immunological function of the tonsillar tissue. However, it is as yet unclear
      whether or not rehypertrophy of this remnant of the tonsils and/or tonsillitis
      reoccur in the long-term. OBJECTIVES: To evaluate the remnants of the tonsils 10
      14 years post-tonsillotomy in children who suffered from obstructive sleep apnea
      syndrome (OSAS) due to obstructive tonsils. METHODS: We conducted a retrospective
      study, telephone survey and selective physical examination of 33 children who had
      obstructive hypertrophic tonsils (suffered from OSAS due to hypertrophic
      tonsils), and underwent tonsillotomy (TT) at Assaf Harofeh Medical Center between
      July 1990 and April 1993, and compared them with a group of 16 children treated
      by tonsillectomy (TE) for the same diagnosis. RESULTS: No statistically
      significant difference was found between the TT and TE groups in all parameters
      compared: non-obstructing tonsils recurred (97% vs. 87%); snoring (3% vs. 12.5%);
      recurrent tonsillitis (6% vs. 6.25%); and recurrent obstruction and unilateral
      enlargement (3% vs. 12.5%). CONCLUSIONS: TT is as effective as TE for the long
      term treatment of children suffering from OSAS due to hypertrophic tonsils.

PMID- 19167100
TI  - Toll-like receptors in tonsillar epithelial cells.
AB  - OBJECTIVE: The Waldeyer's ring, comprised of the nasopharyngeal tonsil, the
      paired tubal tonsils, the paired palatine tonsils, and the lingual tonsil, is
      arranged in a circular orientation around the wall of the throat. The location of
      the palatine tonsils, specifically, enables these structures to come in direct
      contact with potentially harmful inhaled and ingested material that exist in
      their native form since digestive enzymes are not present in the oral cavity.
      Thus, the tonsillar epithelium must not only serve a protective role but it must
      also function in an antigen-sampling role. Previous studies involving the tissues
      of the Waldeyer's ring have been focused on the adaptive immune system, with
      little consideration toward the innate immune system. Studies have demonstrated
      that the tonsils are capable of producing proinflammatory and antiviral cytokines
      and chemokines. In addition, other studies have highlighted the importance of
      epithelial cells in this response. Therefore, we postulate that toll-like
      receptors (TLRs), which recognize components of pathogenic organisms, may play a
      key role in the innate immune response in tonsillar epithelial cells. TLRs are
      innate pattern recognition receptors, which produce proinflammatory cytokines and
      chemokines upon ligation. In this study, we examine the expression and function
      of TLRs in the tonsillar epithelial cell lines, UT-SCC-60A and UT-SCC-60B.
      Additionally, we demonstrate successful isolation of primary tonsillar epithelial
      cells and examine TLR expression in these cells. METHODS: We utilized endpoint RT
      PCR, real time RT-PCR, and flow cytometric analysis to determine TLR expression.
      To assess TLR function, cells were stimulated with TLR ligands and supernatants
      were assayed for secretion of cytokines. RESULTS: UT-SCC-60A and UTSCC-60B
      express TLR mRNA and TLR protein, and the observed responses to the TLR ligands,
      Pam3Cys and Poly I:C suggest that TLR2 and TLR3 are functional in these cells.
      Additionally, primary tonsillar epithelial cells express TLRs. CONCLUSIONS: TLRs
      are expressed in human tonsillar epithelial cells and may play a vital role in
      the immunological outcomes in this tissue.

PMID- 19167101
TI  - Aspirin resistance: what the cardiologist needs to know?
AB  - "Aspirin resistance" can be defined as the inability of aspirin to inhibit
      cyclooxygenase (COX)-1 dependent thromboxane (TX) A2 production, and consequently
      TX A2-dependent platelet functions. Several laboratory methods have been
      proposed, to evaluate platelets' resistance to antiplatelet treatment (bleeding
      time, light transmission aggregation, impedance aggregation, platelet function
      analyser, rapid platelet function assay, TXB2, flow cytometry). However, all
      these methods have their advantages intrinsic limitations. Although aspirin
      resistance appears to be linked to worse long-term outcomes in cardiovascular
      disease patients, clinical treatment of aspirin resistance, including an
      increased aspirin dose or the addition of other antiplatelet drugs, is not often
      effective. Further studies needed to elucidate the appropriate management of
      aspirin resistance.

PMID- 19167102
TI  - Oral triple antiplatelet therapy after percutaneous coronary intervention:
      subject with ongoing arguments?

PMID- 19167103
TI  - Echocardiographic sequence of a cardiac arrest.
AB  - Echocardiographic images have been reported after a cardiac arrest and in
      patients with critical risk for a cardiac arrest. We present the sequence of a
      cardiac arrest in an 82-year-old Italian man with acute myocardial infarction,
      during an echocardiographic evaluation. This case is illustrative of an
      echocardiographic sequence of a cardiac arrest.

PMID- 19167104
TI  - Right ventricular outflow tract obstruction in hypertrophic cardiomyopathy.
AB  - Recently, new cardiac imaging techniques as cardiac magnetic resonance have shown
      to play a primary role for a recognition of unusual mechanisms of right and left
      ventricular obstruction. However, echocardiography remains the most widely used
      technique and the first step to recognize myocardial hypertrophy, blood flow
      velocity, and pressure gradients in real time (2). We describe a rare case of
      hypertrophic cardiomyopathy with isolated obstruction of right ventricular out
      flow where transthoracic echocardiography was able to detect right ventricular
      hypertrophy and obstruction.

PMID- 19167105
TI  - Dilated cardiomyopathy with profound segmental wall motion abnormalities and
      ventricular arrhythmia caused by the R541C mutation in the LMNA gene.
AB  - In laminopathies cardiac involvement is common with dilated cardiomyopathy
      associated with atrio-ventricular block and malignant ventricular arrhythmia
      found in vast majority of patients. However, the specific disease course can be
      very different even among members of the same family which makes genotype
      phenotype correlations difficult. Here we describe a 19-year-old patient with the
      LMNA R541C mutation and compare the course of his disease with two previously
      reported cases of the same molecular defect. We found that our patient shared
      important features with the previously described other subjects: significant LV
      segmental contractility defects (dyskinesis of the inferior wall and akinesis of
      LV apex), the presence of LBBB without atrio-ventricular block on 12-lead
      standard ECG and ICD requirement. The important differences between our subject
      and previously reported cases were early presentation (first symptoms at the age
      of 11 years) and early, progressive LV dilatation. We conclude that the LMNA
      R541C mutation should be considered not only in patients with malignant
      ventricular arrhythmia and LV local wall motion abnormalities, but also in
      classic dilated cardiomyopathy with profound segmental LV contractility defects.

PMID- 19167106
TI  - Association of three lipoprotein lipase polymorphisms with coronary artery
      disease in Chinese and Asian Indians.

PMID- 19167107
TI  - Peripartum cardiomyopathy in a patient with Graves' disease.
AB  - Peripartum cardiomyopathy (PPCM) is a rare life-threatening cardiomyopathy of
      unknown etiology that occurs during the peripartum period in previously healthy
      women. Autoimmune and viral factors have been suggested to be involved in PPCM.
      Here we describe a patient with Graves' disease, which is one of the organ
      specific autoimmune diseases, who developed acute heart failure due to PPCM at 2
      weeks after her first delivery. The patient recovered completely with
      conservative treatment for heart failure. An association between PPCM and Graves'
      disease has not been reported before. PPCM may be an organ-specific autoimmune
      disease, so the coexistence of other autoimmune diseases should be considered in
      PPCM patients.

PMID- 19167108
TI  - Exercise-test-related heart rate variability and mortality: the Finnish
      Cardiovascular Study.

PMID- 19167109
TI  - Why first degree relatives of coronary artery disease patient's have Chlamydia
      pneumoniae infection.
AB  - Chlamydia pneumoniae (C. pneumoniae) infection in coronary artery disease (CAD)
      is confirmed by many workers. However our knowledge on relationship between
      infection and atherosclerosis is still in infancy. In this report we discuss why
      should relatives of patients with CAD have contracted C. pneumoniae infection?

PMID- 19167110
TI  - Atorvastatin attenuates post-implant tissue degeneration of cardiac prosthetic
      valve bovine pericardial tissue in a subcutaneous animal model.
AB  - AIMS: The aim of our study was to examine the effects of statin therapy
      (atorvastatin) on post-implant structural changes of bovine pericardial tissue in
      a subcutaneous animal model. METHODS AND RESULTS: Sixty male C57BL/6 mice
      underwent subcutaneous dorsal implantation of bovine pericardial fragments.
      Animals were randomized to treatment with atorvastatin (50 mg/kg) (statin group -
      SG) or to vehicle (control group - CG). After 1.5 months, all fragments were
      explanted and submitted to histopathological assessment (semi-quantitative
      analysis) to elucidate extent of inflammatory infiltrate, signs of tissue injury,
      or presence of microcalcification. Calcium determination of the implanted
      pericardial tissue was also performed by inductively coupled plasma mass
      spectrometry (ICP-MS) assessment. ICP-MS analysis showed that pericardial
      fragments in SG had significantly (p<0.01) less calcium content than CG (625+/
      142 vs. 962+/-590 microg/g, respectively). Light microscopy showed marked
      inflammatory infiltrates and tissue injury of pericardial specimens in CG
      animals, whereas SG animals maintained a better preserved original pericardial
      structure. CONCLUSIONS: Our findings indicate that atorvastatin significantly
      attenuates the post-implant structural degeneration of artificial valve bovine
      pericardial tissue in a subcutaneous animal model. Further observations are
      mandatory to assess the effects of statins on the implanted bioprosthetic valve
      tissue in the blood circulation.

PMID- 19167111
TI  - Magnetic resonance imaging of a hypereosinophilic endocarditis with apical
      thrombotic obliteration in Churg-Strauss syndrome complicated with acute
      abdominal aortic embolic occlusion.
AB  - Churg-Strauss syndrome can be associated with Loeffler-like eosinophilic
      endocarditis. We report a case of a young woman in which the diagnosis of Churg
      Strauss syndrome was made subsequently to the magnetic resonance demonstration of
      eosinophilic endocarditis associated to left ventricle apical thrombosis. In our
      report, this rare condition evolved in an unusual complication: the embolic
      migration of the left ventricle apical thrombus in the abdominal aorta as showed
      by multi-detector-computed-tomography angiography.

PMID- 19167112
TI  - Similarities between ischemic preconditioning and postconditioning in myocardial
      ischemia/reperfusion injury.

PMID- 19167113
TI  - Coronary allograft vasculopathy and coronary vasospasm in heart transplant
      recipients: a manifestation of Kounis syndrome?
AB  - The pathophysiology of vasculopathy of cardiac allografts is still unknown.
      Coronary vasospasm and thrombosis are some rare manifestations accompanying this
      entity. Hypersensitivity processes and the hypersensitivity coronary syndrome
      (Kounis syndrome) may be associated with this potentially fatal complication.
      Research efforts towards this direction may shed light for prevention and
      treatment of this disease.

PMID- 19167114
TI  - A-V nodal artery anatomy and relations to the posterior septal space and its
      contents.
AB  - BACKGROUND AND AIM: Radiofrequency catheter ablation treats resistant nodal re
      entrant tachycardia but carries a risk to AV conduction system and its vessels.
      We aimed to study the origin of the A-V nodal artery (AVNA) and its course within
      the posterior septal space (PSS). METHODS: Twenty embalmed human hearts of both
      sexes (16 males) age, 25-60 years, were dissected to study the PPS and its
      arteries down to their destination. RESULTS: The PSS is a four sided pyramidal
      space, at the crux of the heart, with its base made of the pericardium. It is
      made of four; right upper and lower and left upper and lower walls corresponding
      to the right atrium and ventricle and left atrium and ventricle, respectively.
      The right coronary artery (RCA) crossed the base from the right to the left
      angle, to lie inferior and adherent to the terminal part of the coronary sinus
      (CS). The posterior interventricular artery, the ventricular branches of the RCA,
      the middle cardiac vein and the ventricular veins, all crossed the base of the
      space to their final destination. AVNA originated from either the RCA itself or
      one of its branches. Double AVNA was encountered in 14 specimens with the upper
      artery larger and passed between the right and left atria and the lower artery
      smaller and crossed the space adjacent to the right ventricle. CONCLUSIONS: These
      findings highlight the importance of the PSS and its structural relations, in
      particular to the AVNA, that should be considered during various interventional
      procedures.

PMID- 19167115
TI  - Intermittent changing axis deviation during acute myocarditis.
AB  - It has been rarely reported intermittent changing axis deviation also during
      atrial fibrillation and also during atrial flutter. Intermittent changing axis
      deviation during acute myocardial infarction and changing axis deviation
      associated with atrial fibrillation and acute myocardial infarction too have been
      also rarely reported. Conduction system disturbances have been described during
      acute myocarditis and it has been suggested that myocardial interstitial edema is
      implicated in the conduction disturbances that occur in acute myocarditis.
      Usually, edema is located in the epicardial layer of ventricular wall during
      acute phase of focal myocarditis and it can't be associated with clear evidence
      of wall motion abnormalities. It has also been described in a work the report of
      sequences of alternatively normal and Wenckebach beats with alternate and
      progressive right bundle branch block interpreted as functional longitudinal
      dissociation in atrioventricular conduction axis during chronic chagasic
      myocarditis. We present a case of changing axis deviation during acute
      myocarditis in a 15-year-old Italian man. This case focuses attention on changing
      axis deviation during acute phase of focal myocarditis in absence of wall motion
      abnormalities.

PMID- 19167116
TI  - Assessment of the effects of supplementation with vitamin E on health and
      production of feedlot cattle using meta-analysis.
AB  - Delivery of supplemental antioxidant vitamins to cattle placed in feedlots might
      be expected to improve health and performance outcomes by reducing the effects of
      oxidative stress to which these cattle are presumably exposed. Meta-analytic
      procedures were used in this study to assess published experiments on the effects
      of vitamin E supplementation in feedlot cattle. The health outcome of morbidity,
      and the production outcomes of average daily gain (ADG) and gain to feed ratio
      (G:F), were analysed. The currently available data do not support the use of
      supplemental vitamin E administered as an injection (morbidity risk ratio=1.17;
      P=0.17). The authors conclude that supplemental dietary vitamin E should be fed
      within the [NRC, 1996. National Research Council. Nutrient Requirements of Beef
      Cattle, 7th ed. Natl. Acad. Press, Washington, DC] recommended range.

PMID- 19167117
TI  - Correcting the concentration index: a comment.
AB  - In a recent article in this journal, Erreygers [Erreygers, G., 2008. Correcting
      the concentration index. Journal of Health Economics] has proposed a new measure
      of income-related health inequality to overcome three shortcomings of the
      concentration index (CI). I think Erreygers is absolutely right to probe on these
      issues, and I welcome his generalization of my normalization which was specific
      to the case of a binary health indicator. However, I have misgivings about his
      paper. His goal of correcting the CI so as to make it usable with interval-scale
      variables seems misguided. The CI reflects a commitment on the part of the
      analyst to measuring relative inequality. Armed only with an interval-scale
      variable, one simply has to accept that one can meaningfully measure only
      differences and therefore settle for measuring absolute inequality. Erreygers,
      index inevitably ends up as a measure of absolute inequality. His objection to my
      approach to getting round the bounds problem is that my normalization of the CI
      does not produce a measure of absolute inequality. But that was never my
      intention! In this comment I also show that - somewhat paradoxically at first
      glance - my index is also not a pure index of relative inequality. This seems to
      be an inevitable consequence of tackling the bounds issue.

PMID- 19167118
TI  - Relation between elective nodal failure and irradiated volume in non-small-cell
      lung cancer (NSCLC) treated with radiotherapy using conventional fields and
      doses.
AB  - INTRODUCTION: The role of elective nodal irradiation of non-small-cell lung
      cancer (NSCLC) patients treated with radiotherapy remains unclear. We
      investigated the significance of treating clinically uninvolved lymph nodes by
      retrospectively analyzing the relationship between loco-regional failure and the
      irradiated volume. METHODS: Between 1998 and 2003, patients with IA-IIIB NSCLC
      were treated with radiotherapy. The eligibility criteria for this study were an
      irradiation dose of 60Gy or more and a clinical response better than stable
      disease. Typical radiotherapy consisted of 40 Gy/20 fr to the tumor volumes
      (clinical target volume of the primary tumor [CTVp], of the metastatic lymph
      nodes [CTVn], and of the subclinical nodal region [CTVs]), followed by off-cord
      boost to CTVp+n to a total dose 60-68 Gy/30-34 fr. The relationship between the
      sites of recurrence and irradiated volumes was analyzed. RESULTS: A total of 127
      patients fulfilled the eligibility criteria. Their median overall and progression
      free survival times were 23.5 (range, 4.2-109.7) and 9.0 months (2.2-109.7),
      respectively. At a median follow-up time of 50.5 months (range, 14.2-83.0) for
      the surviving patients, the first treatment failure was observed in 95 patients
      (loco-regional; 41, distant; 42, both; 12). Among the patients with loco-regional
      failure, in-field recurrence occurred in 38 patients, and four CTVs recurrences
      associated with CTVp+n failure were observed. No isolated recurrence in CTVs was
      observed. CONCLUSIONS: In-field loco-regional failure, as well as distant
      metastasis, was a major type of failure, and there was no isolated elective nodal
      failure. Radiation volume adequacy did not seem to affect elective nodal failure.

PMID- 19167119
TI  - Eight years experience of local prostate cancer treatment with permanent I125
      seed brachytherapy--morbidity and outcome results.
AB  - BACKGROUND AND PURPOSE: There are only a limited number of reports of treatment
      of prostate cancer with permanent prostate seed I(125) brachytherapy (PPB) in
      Europe. We describe results from one Finnish institution having treated 444
      patients with a follow-up of eight years. MATERIAL AND METHODS: Morbidity was
      evaluated by International Prostate Symptom Score and International Index of
      Erectile Function questionnaires. Urine flow, residual urine volume and the PSA
      values were measured pre-treatment and during follow-up. Any additional
      treatments were recorded. RESULTS: PPB was well tolerated. Median IPSS increased
      from 8 at baseline to 18 at three months post-therapy and returned to baseline
      score within 12 months. Median urine flow decreased from 15.2 ml/s at baseline to
      10.2 ml/s at three months and returned to baseline value within two years. Acute
      urinary retention, potency preservation and severe proctitis were observed in
      11%, 86% and 2% of patients, respectively. The PSA bounce was observed in 13% and
      PSA nadir < or =0.5 microg/l was reached by 81% of patients. Disease-free
      survival (DFS) was 90.2%. In the Cox regression analysis, the independent
      predictors of DFS were risk group and PSA nadir < or =0.5 microg/l (p<0.0001 for
      both). PC-specific survival was 98.5% and overall survival was 94.6%.
      CONCLUSIONS: Our results are in concordance and comparable with other reports on
      PPB.

PMID- 19167120
TI  - A predictive model for swallowing dysfunction after curative radiotherapy in head
      and neck cancer.
AB  - INTRODUCTION: Recently, we found that swallowing dysfunction after curative
      (chemo) radiation (CH) RT has a strong negative impact on health-related quality
      of life (HRQoL), even more than xerostomia. The purpose of this study was to
      design a predictive model for swallowing dysfunction after curative radiotherapy
      or chemoradiation. MATERIALS AND METHODS: A prospective study was performed
      including 529 patients with head and neck squamous cell carcinoma (HNSCC) treated
      with curative (CH) RT. In all patients, acute and late radiation-induced
      morbidity (RTOG Acute and Late Morbidity Scoring System) was scored
      prospectively. To design the model univariate and multivariate logistic
      regression analyses were carried out with grade 2 or higher RTOG swallowing
      dysfunction at 6 months as the primary (SWALL(6months)) endpoint. The model was
      validated by comparing the predicted and observed complication rates and by
      testing if the model also predicted acute dysphagia and late dysphagia at later
      time points (12, 18 and 24 months). RESULTS: After univariate and multivariate
      logistic regression analyses, the following factors turned out to be independent
      prognostic factors for SWALL(6months): T3-T4, bilateral neck irradiation, weight
      loss prior to radiation, oropharyngeal and nasopharyngeal tumours, accelerated
      radiotherapy and concomitant chemoradiation. By summation of the regression
      coefficients derived from the multivariate model, the Total Dysphagia Risk Score
      (TDRS) could be calculated. In the logistic regression model, the TDRS was
      significantly associated with SWALL(6months) ((p<0.001). Subsequently, we defined
      three risk groups based on the TDRS. The rate of SWALL(6months) was 5%, 24% and
      46% in case of low-, intermediate- and high-risk patients, respectively. These
      observed percentages were within the 95% confidence intervals of the predicted
      values. The TDRS risk group classification was also significantly associated with
      acute dysphagia (P<0.001 at all time points) and with late swallowing dysfunction
      at 12, 18 and 24 months (p<0.001 at all time points). CONCLUSION: The TDRS is a
      simple and validated measure to predict swallowing dysfunction after curative
      (CH) RT for HNC. This classification system enables identification of patients
      who may benefit from strategies aiming at prevention of swallowing dysfunction
      after curative (CH) RT such as preventive swallowing exercises during treatment
      and/or emerging IMRT techniques aiming at sparing anatomical structures that are
      involved in swallowing.

PMID- 19167121
TI  - Association of urethral toxicity with dose exposure in combined high-dose-rate
      brachytherapy and intensity-modulated radiation therapy in intermediate- and high
      risk prostate cancer.
AB  - INTRODUCTION: To report acute and late toxicities in patients with intermediate-
      and high-risk prostate cancer treated with combined high-dose-rate brachytherapy
      (HDR-B) and intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS:
      From March 2003 to September 2005, 64 men were treated with a single implant HDR
      B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ
      tracking. Median age was 66.1 years, and risk of recurrence was intermediate in
      47% of the patients or high in 53% of the patients. Androgen deprivation therapy
      was received by 69% of the patients. Toxicity was scored according to the CTCAE
      version 3.0. Median follow-up was 3.1 years. RESULTS: Acute grade 3 genitourinary
      (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU
      toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3
      gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late
      grade 3 GI toxicity was absent. The urethral V(120) (urethral volume receiving >
      or =120% of the prescribed HDR-B dose) was associated with acute (P=.047) and
      late > or = grade 2 GU toxicities (P=.049). CONCLUSIONS: Late grades 3 and 4GU
      toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT
      in association with the irradiated urethral volume. The impact of V(120) on GU
      toxicity should be validated in further studies.

PMID- 19167122
TI  - A randomized phase II study of cisplatin/5-FU concurrent chemoradiotherapy for
      esophageal cancer: Short-term infusion versus protracted infusion chemotherapy
      (KROSG0101/JROSG021).
AB  - PURPOSE: A randomized phase II study was conducted to compare the toxicity and
      efficacy of combining short-term chemotherapy (CT) or protracted CT with
      radiotherapy (RT) for esophageal cancer. MATERIALS AND METHODS: Eligible patients
      were <75 years and with performance status (PS) of 0-2, and had stages II-IVA
      esophageal cancer. Two cycles of cisplatin 70 mg/m(2) for 1 day and 5FU 700
      mg/m(2) for 5 days (arm A) or cisplatin 7 mg/m(2) for 10 days and 5FU 250 mg/m(2)
      for 14 days (arm B) were given with RT of 60Gy/30 fractions/7 weeks (1-week
      split). RESULTS: Of 91 patients enrolled, 46 were randomized to arm A and 45 to
      arm B. Two cycles of CT were given concurrently with RT for 89% in arm A and for
      71% in arm B with significant difference (P=.031). The 2- and 5-year overall
      survival rates for arm A were 46% and 35%, while those for arm B were 44% and
      24%, respectively, without significant difference. The 2- and 5-year progression
      free survival rates for arm A were 30% and 30%, while those for arm B were 29%
      and 12%, respectively. CONCLUSIONS: Protracted infusion CT with RT provides no
      advantage over standard short-term infusion CT with RT for esophageal cancer.

PMID- 19167123
TI  - Accelerated partial breast irradiation utilizing balloon brachytherapy
      techniques.
AB  - To overcome the barriers to BCT, methods of PBI in the setting of breast
      conservation have been explored. The method of PBI with the longest published
      follow-up is multi-catheter interstitial brachytherapy. Balloon-based
      brachytherapy with the MammoSite brachytherapy applicator was designed to
      simplify the brachytherapy procedure for PBI, enhance the reproducibility of the
      dosimetry, and improve patient comfort. The rates of local recurrence following
      PBI with the MammoSite applicator have been low, but there are few published
      reports and follow-up has been relatively short. The cosmetic outcomes and
      toxicity of MammoSite PBI are comparable to those seen after multicatheter-based
      PBI. Additional methods of balloon brachytherapy, including Xoft and SenoRx
      Contura have been developed. Finally, long-term follow-up after PBI is important
      for the welfare of individual patients and in order to establish the efficacy,
      late toxicity and cosmetic outcomes of this technique.

PMID- 19167124
TI  - Inactivation of Enterobacter sakazakii by water-soluble muscadine seed extracts.
AB  - Hot and cold water-soluble muscadine (Vitis rotundifolia) seed extracts and their
      polar and polyphenol fractions from two Muscadine cultivars ('Ison', purple and
      'Carlos', bronze) were investigated for their inhibition of Enterobacter
      sakazakii. The heat treatment on each seed extract not only increased total
      phenolics and tannic acid but also enhanced antimicrobial activity against two
      strains of E. sakazakii. Within 1 h, all seed extracts reduced an initial
      population (approximately 6 log CFU/mL) of E. sakazakii to a non-detectable level
      (minimum detection limit, 10 CFU/mL). Regardless of extraction method and
      cultivar, only the polar fractions which contained malic, tartaric and tannic
      acids showed antimicrobial activity against two strains of E. sakazakii. The
      polyphenol fractions which contained gallic acid, catechin, epicatechin, ellagic
      acid and pigments showed slight inhibition against E. sakazakii. Results showed
      that water-soluble muscadine seed extracts (pH 3.3-3.78) contained strong
      antimicrobial inhibitors against E. sakazakii while acidified peptone water (pH
      3.3) did not show any antimicrobial activity.

PMID- 19167125
TI  - Two outbreaks of campylobacteriosis associated with the consumption of raw cows'
      milk.
AB  - The present paper summarises the investigation of two different outbreaks of milk
      associated Campylobacter enteritis in the Netherlands. In 2005, after a school
      trip to a dairy farm, 22 out of a group of 34 children developed diarrhoeal
      illness and Campylobacterjejuni was cultured from the stool samples of 11 of the
      cases. The illness was found to be epidemiologically associated with drinking raw
      milk during the farm visit; 86% of the cases could be explained by drinking raw
      milk. C.jejuni was also isolated from three of 10 faecal samples from dairy
      cattle collected at the farm. The human isolates and C.jejuni isolates from one
      of these three samples of cattle faeces revealed identical restriction patterns
      by both pulsed-field gel electrophoresis (PFGE) and flagellin (fla) typing by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
      Both epidemiological and bacteriological evidence implicated contaminated raw
      milk as the vehicle of transmission, though C.jejuni was not isolated from the
      bulk tank milk or the milk filter collected during the farm investigation. In
      2007, an outbreak of enteritis was notified among people who had attended a lunch
      at a dairy farm where bulk tank milk was served. Of the 19 persons who had
      consumed raw milk, 16 (84%) had become ill. Of the persons who did not drink the
      raw milk, none became ill. A significant association was found between tasting
      the raw milk and being ill (risk difference=0.84, p=0.0011). C.jejuni was
      cultured from four of seven cases who had submitted a stool specimen. C. jejuni
      was also isolated from a sample of bulk tank milk and the isolate had an
      identical flaA PCR-RFLP genotype to isolates obtained from patients. Also in this
      outbreak both the epidemiological and bacteriological findings support raw milk
      as the vehicle for the enteritis. These two outbreaks highlight the health risks
      associated with the consumption of raw milk. As long as legislation allows the
      sale and distribution of untreated milk these risks will continue. Therefore,
      consumers need to be continuously informed about the dangers inherent in
      consuming unpasteurised milk or products made from raw milk. Farmers need to be
      strongly discouraged from serving raw milk to their visitors.

PMID- 19167126
TI  - Production of gamma-aminobutyric acid in black raspberry juice during
      fermentation by Lactobacillus brevis GABA100.
AB  - Black raspberry juice was fermented to produce gamma-aminobutyric acid (GABA)
      using lactic acid bacteria (Lactobacillus brevis GABA 100) at different
      temperatures (25, 30, or 37 degrees C) and pHs (3.5, 4, 4.5, 5, 5.5, or 6) for 15
      days. Concentrations of GABA in the juices were determined during fermentation
      using HPLC. GABA was produced continuously even if the viable bacterial counts
      markedly decreased. The fermentation at 30 degrees C generally showed higher
      production of GABA in the juices than those at 25 and 37 degrees C. The GABA in
      the juices fermented at 30 degrees C reached the maximum levels on the 12th day.
      The juices fermented at lower pH and lower temperature showed a lower degradation
      of monomeric anthocyanins. The results suggest that black raspberry juice can be
      GABA enriched using lactic acid bacteria.

PMID- 19167127
TI  - Persistence with statin therapy in diabetic and non-diabetic persons: a nation
      wide register study in 1995-2005 in Finland.
AB  - Persistence with statin therapy was studied among 562 598 new statin users in
      1995-2005 in Finland. Discontinuation was most likely during the first year.
      Persons with diabetes (15.0% of initiators) were significantly more likely to
      continue statin therapy compared with person not having diabetes.

PMID- 19167128
TI  - Willingness to pay for weight-control treatment.
AB  - OBJECTIVES: To estimate willingness to pay (WTP) for alternative forms of weight
      control treatment and evaluate how it varies with individual characteristics.
      METHODS: Contingent valuation (CV) survey of employed females in Taiwan using
      double-bounded dichotomous-choice question format and telephone interview.
      Statistical models include an estimated correction for sample-selection bias
      associated with respondents' interest in weight loss. RESULTS: Estimated WTP is
      strongly and positively associated with younger age, greater personal income,
      higher body weight, adverse personal weight perceptions, and greater peer
      pressure for weight control. There is a little evidence of sample-selection bias
      associated with the decision to lose weight. Estimated WTP for a weight-loss
      medicine is about US$ 12 per month, larger than estimated WTP for a low-calorie
      diet of about US$ 10 per month. CONCLUSIONS: WTP for weight-control treatment
      among women in Taiwan is significant and related to individual characteristics
      such as age, income, and perceptions about current and optimal weight.

PMID- 19167129
TI  - Fast calculation of pairwise mutual information for gene regulatory network
      reconstruction.
AB  - We present a new software implementation to more efficiently compute the mutual
      information for all pairs of genes from gene expression microarrays. Computation
      of the mutual information is a necessary first step in various information
      theoretic approaches for reconstructing gene regulatory networks from microarray
      data. When the mutual information is estimated by kernel methods, computing the
      pairwise mutual information is quite time-consuming. Our implementation
      significantly reduces the computation time. For an example data set of 336
      samples consisting of normal and malignant B-cells, with 9563 genes measured per
      sample, the current available software for ARACNE requires 142 hours to compute
      the mutual information for all gene pairs, whereas our algorithm requires 1.6
      hours. The increased efficiency of our algorithm improves the feasibility of
      applying mutual information based approaches for reconstructing large regulatory
      networks.

PMID- 19167131
TI  - Integral quantification of contaminant mass flow rates in a contaminated aquifer:
      conditioning of the numerical inversion of concentration-time series.
AB  - A series of integral pumping tests (IPTs) has been conducted at a former gasworks
      site to quantify the contaminant mass flow rates and average concentration in
      groundwater along three control planes across the groundwater flow direction. The
      measured concentration-time series were analysed numerically with the help of the
      inversion code CSTREAM and a flow and transport model representing the highly
      heterogeneous aquifer. Since the control planes cover the entire downstream width
      of the potentially contaminated area, they allow conclusions to be drawn about
      the current location and spread of the contaminant plume. Previous evaluations of
      integral pumping tests could calculate three scenarios concerning the spread of
      the plume around the IPT well: (i) the plume is located to the right of the
      pumping well, (ii) to the left, or (iii) is distributed symmetrically around it.
      To create a more realistic picture of the plume position, a series of direct-push
      monitoring wells were installed along one control plane. The concentrations found
      in these wells were included in the numerical analysis to condition the numerical
      inversion results, and allowed the identification of a more pronounced plume
      centre and fringe, which supports the development of optimised remediation
      strategies.

PMID- 19167130
TI  - A phase II trial of pemetrexed and gemcitabine as first line therapy for poor
      performance status and/or elderly patients with stage IIIB/IV non-small cell lung
      cancer.
AB  - Pemetrexed and gemcitabine are both active agents for the treatment of locally
      advanced or metastatic NSCLC. We tested a novel biweekly combination of
      pemetrexed and gemcitabine for tolerability and efficacy in 45 elderly and/or
      poor performance status patients (44% female, mean age of 72.4 years) with
      measurable stage IIIB/IV NSCLC. Patients received biweekly cycles of pemetrexed
      500 mg/m(2) IV over 10 min followed by gemcitabine 1500 mg/m(2) IV with vitamin
      B12 1000 microg IM, and folic acid 1mg po daily beginning 7 days before and
      continuing throughout treatment (median of 4 cycles). Ten patients experienced
      grade 3/4 neutropenia, two had grade 3 febrile neutropenia, and two had grade 3
      anemia. Patients with ECOG PS 2 appeared poorly suited for the regimen, with
      61.5% completing < or = 2 cycles. The overall response rate was 17.8%, the
      clinical benefit rate (CR+PR+SD >24 weeks) was 26.7%, and the median progression
      free survival was 3.5 months. However, ECOG 0-1 patients had longer PFS and
      tended to have a better response rate than ECOG 2 patients.

PMID- 19167132
TI  - Performance of a zerovalent iron reactive barrier for the treatment of arsenic in
      groundwater: Part 2. Geochemical modeling and solid phase studies.
AB  - Arsenic uptake processes were evaluated in a zerovalent iron reactive barrier
      installed at a lead smelting facility using geochemical modeling, solid-phase
      analysis, and X-ray absorption spectroscopy techniques. Aqueous speciation of
      arsenic is expected to play a key role in directing arsenic uptake processes.
      Geochemical modeling reveals contrasting pH-dependencies for As(III) and As(V)
      precipitation. At the moderately alkaline pH conditions typically encountered in
      zerovalent iron reactive barriers, As(III) is unlikely to precipitate as an oxide
      or a sulfide phase. Conversely, increasing pH is expected to drive precipitation
      of metal arsenates including ferrous arsenate. Bacterially mediated sulfate
      reduction plays an important role in field installations of granular iron.
      Neoformed iron sulfides provide surfaces for adsorption of oxyanion and
      thioarsenic species of As(III) and As(V) and are expected to provide enhanced
      arsenic removal capacity. X-ray absorption near edge structure (XANES) spectra
      indicate that arsenic is sequestered in the solid phase as both As(III) and As(V)
      in coordination environments with O and S. Arsenic removal in the PRB probably
      results from several pathways, including adsorption to iron oxide and iron
      sulfide surfaces, and possible precipitation of ferrous arsenate. Corrosion of
      granular iron appears to result in some As(III) oxidation to As(V) as the
      proportion of As(V) to As(III) in the solid phase is greater compared to influent
      groundwater. As(0) was not detected in the PRB materials. These results are
      broadly comparable to laboratory based studies of arsenic removal by zerovalent
      iron, but additional complexity is revealed in the field environment, which is
      largely due to the influence of subsurface microbiota.

PMID- 19167133
TI  - Performance of a zerovalent iron reactive barrier for the treatment of arsenic in
      groundwater: Part 1. Hydrogeochemical studies.
AB  - Developments and improvements of remedial technologies are needed to effectively
      manage arsenic contamination in groundwater at hazardous waste sites. In June
      2005, a 9.1 m long, 14 m deep, and 1.8 to 2.4 m wide (in the direction of
      groundwater flow) pilot-scale permeable reactive barrier (PRB) was installed at a
      former lead smelting facility, located near Helena, Montana (USA). The reactive
      barrier was designed to treat groundwater contaminated with moderately high
      concentrations of both As(III) and As(V). The reactive barrier was installed over
      a 3-day period using bio-polymer slurry methods and modified excavating equipment
      for deep trenching. The reactive medium was composed entirely of granular iron
      which was selected based on long-term laboratory column experiments. A monitoring
      network of approximately 40 groundwater sampling points was installed in July
      2005. Monitoring results indicate arsenic concentrations >25 mg L(-1) in wells
      located hydraulically upgradient of the PRB. Of 80 groundwater samples collected
      from the pilot-PRB, 11 samples exceeded 0.50 mg As L(-1); 62 samples had
      concentrations of arsenic at or below 0.50 mg L(-1); and, 24 samples were at or
      below the maximum contaminant level (MCL) for arsenic of 0.01 mg L(-1). After 2
      years of operation, monitoring points located within 1 m of the downgradient edge
      of the PRB showed significant decreases in arsenic concentrations at depth
      intervals impacted by the emplaced zerovalent iron. This study indicates that
      zerovalent iron can be effectively used to treat groundwater contaminated with
      arsenic given appropriate groundwater geochemistry and hydrology. The study also
      further demonstrates the shortcomings of hanging-wall designs. Detailed
      subsurface characterization data that capture geochemical and hydrogeologic
      variability, including a flux-based analysis, are needed for successful
      applications of PRB technology for arsenic remediation.

PMID- 19167134
TI  - Morphophysiology of the Zuckerkandl's paraganglion: effects of dexamethasone and
      aging.
AB  - The extra-adrenal Zuckerkandl's paraganglion is used as a source of chromaffin
      cells for transplantation in parkinsonian animals. Aging can affect its
      viability, and this tissue needs further characterization for improving grafting
      procedures. The objectives were: (i) to compare the main morpho-functional
      characteristics of prepubertal and old Zuckerkandl's paraganglion (ZP), and (ii)
      to discern phenotypic changes after sub-chronic dexamethasone treatment in extra
      adrenal tissue of prepubertal rats. For these purposes, immunostaining methods,
      stereology, voltammetry, cell culture, Western blotting, and ELISA were employed.
      The findings revealed that all paraganglia were composed of mesenchymal tissue
      and chromaffin cells. In prepubertal rats, chromaffin cells are arranged as large
      or small clusters. Large clusters (also known as "cell nests") contain densely
      packed chromaffin cells, and they are seen as fascicles in longitudinal sections.
      In old paraganglia, cell nests disappear, and chromaffin cells are found to be
      arranged as small cell clusters or dispersed throughout the mesenchyma.
      Paraganglionic chromaffin cells possess a rounded morphology with diameter
      ranging from 12 to 15 MUm, with intracytoplasmic granules (100-500 nm in
      diameter) containing catecholamines. Prepubertal and old ZP chromaffin cells are
      mostly noradrenergics, and a few of them are dopaminergics. Aging reduces the
      amount of chromaffin tissue (28% in adult rats vs. 11% in old animals, both in
      relation to total volume of the paraganglion), and induces the presence of
      adrenergic cells and adrenaline. Both prepubertal and old cells express the
      neurotrophic factors GDNF and TGF-beta1, aging leading to reduced levels of both
      growth factors. Dexamethasone (50 MUg/kg daily, 5 days) leads to the expression
      of phenylethanolamine-N-methyl-transferase in prepubertal paraganglia, and to a
      higher content and release of adrenaline.

PMID- 19167135
TI  - CoMFA and docking studies of 2-phenylindole derivatives with anticancer activity.
AB  - Three-dimensional (3D) quantitative structure-activity relationship (QSAR) and
      docking studies of 43 tubulin inhibitors, 2-phenylindole derivatives with
      anticancer activity against human breast cancer cell line MDA-MB 231, have been
      carried out. The established 3D-QSAR model from the comparative molecular field
      analysis (CoMFA) in training set shows not only significant statistical quality,
      but also satisfying predictive ability, with high correlation coefficient value
      (R(2)=0.910) and cross-validation coefficient value (q(2)=0.705). Moreover, the
      predictive ability of the CoMFA model was further confirmed by a test set, giving
      the predictive correlation coefficient (R(2)(pred)) of 0.688. Based on the CoMFA
      contour maps and docking analyses, some key structural factors responsible for
      anticancer activity of this series of compounds were revealed as follows: the
      substituent R(1) should have higher electronegativity; the substituent R(2)
      should be linear alkyl with four or five carbon atoms in length; and the
      substituent R(3) should be selected to OCH(3)-kind group whereas should not be
      selected to CF(3)-kind group. Meanwhile, the interaction information between
      target and ligand was presented in detail. Such results can offer some useful
      theoretical references for understanding the action mechanism, designing more
      potent inhibitors and predicting their activities prior to synthesis.

PMID- 19167136
TI  - Synthesis of some new 1,3,4-thiadiazol-2-ylmethyl-1,2,4-triazole derivatives and
      investigation of their antimicrobial activities.
AB  - 4-Amino-2-[(5-arylamino-4,5-dihydro-1,3,4-thiadiazol-2-yl)methyl]-5-(4
      methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones (3a-c) were obtained in acidic
      media via the formation of 2-[(4-amino-3-aryl-5-oxo-4,5-dihydro-1H-1,2,4-triazol
      1-yl)acetyl]-N-arylhydrazinecarbothioamides (2a-c), and then, compound 3b was
      converted to methylated derivative, 4. The basic treatment of carbothioamide
      derivatives, 2a-c, afforded 4-amino-2-[(4-aryl-5-sulphanyl-4H-1,2,4-triazol-3
      yl)methyl]-5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones (5a-c). The
      alkylation reactions of compounds 4H-1,2,4-triazol-3-ylmethyl-5-(4-methylphenyl)
      2,4-dihydro-3H-1,2,4-triazol-3-one derivatives (5a-c) were performed by using
      methyl iodide or ethyl bromide in the presence of sodium ethoxide, while the
      treatment of the same intermediates, 5a-c, with aromatic aldehydes produced 2-{[4
      (4-aryl)-5-sulphanyl-4H-1,2,4-triazol-3-yl]methyl}-4-(arylmethylene)amino-5-(4
      methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones (8a-d). The synthesis of 4
      amino-(or arylideneamino)-5-(4-methylphenyl)-2-{[(4-methylpiperazin-1-yl or
      morpholin-4-ylethyl)methyl]-4-aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3
      yl}methyl-2,4-dihydro-3H-1,2,4-triazol-3-ones (7a, b and 9) was performed by a
      one pot three-component Mannich reaction involving the corresponding compounds, 4
      (substituted)amino-4H-1,2,4-triazol-3-ylmethyl-5-(4-methylphenyl)-2,4-dihydro-3H
      1,2,4-triazol-3-one derivatives 5a, b and 8a, methylpiperazine or 2-(4
      morpholino)ethylamine and formaldehyde. The newly synthesized compounds were well
      characterized by elemental analyses, IR, (1)H NMR, (13)C NMR and mass spectral
      studies. They were also screened for their microbial activities. The
      antimicrobial activity study revealed that some of which 2a, c, 3c, 5a-c, 8a-d
      showed good activity against a variety of microorganisms.

PMID- 19167137
TI  - Metastasis of amelanotic melanoma of unknown origin in the parotid gland.
AB  - We report a rare case of metastasis of an amelanotic melanoma of the parotid
      gland. To our knowledge this is the first report of a metastasis of an amelanotic
      melanoma in a parotid lymph node. Superficial parotidectomy with no other
      complementary treatment controlled the tumour. Progress has been excellent and
      the patient was well at six years' follow-up.

PMID- 19167138
TI  - Integrating a developmental perspective in dimensional models of personality
      disorders.
AB  - There is growing evidence that manifestations of personality pathology are
      traceable in early years of life. Nevertheless, the existing diagnostic
      nomenclature contains little recognition of childhood antecedents of adult
      personality disorders (PD). The current paper suggests that these childhood
      antecedents are more readily recognized to the extent that the personality
      disorders are themselves understood as configurations of extreme Five-Factor
      Model personality traits. From this dimensional perspective, we propose the
      Dimensional Personality Symptom Itempool (DIPSI), an age-specific model for
      describing child and adolescent trait pathology. We suggest that the DIPSI
      represents a comprehensive conceptualization of childhood PD antecedents and may
      contribute to the understanding of the developmental course of personality
      disorders. Issues and concerns to further elaborate this life-span perspective on
      personality disorders are discussed.

PMID- 19167139
TI  - The role of stress on close relationships and marital satisfaction.
AB  - Stress is a concept that has received increased attention in marital research
      during the last decade, showing that it plays an important role in understanding
      the quality and stability of close relationships. Evidence suggests that stress
      is a threat to marital satisfaction and its longevity. Research has been based
      upon theoretical models of stress in close relationships, specifically family
      stress models [e.g., Hill, R. (1958). Generic features of families under stress.
      Social Casework, 39, 139-150.; McCubbin, H. I., & Patterson, J. M. (1983). Family
      transitions: Adaptation to stress. In H. I. McCubbin & C. R. Figley (Eds.),
      Stress and the family: Coping with normative transitions (Vol. 2, pp. 5-25). New
      York: Brunner/Mazel] and couple's stress model's proposed by Karney, Story, and
      Bradbury [Karney, B. R., Story, L. B., & Bradbury, T. N. (2005). Marriages in
      context: Interactions between chronic an acute stress among newlyweds. In T. A.
      Revenson, K. Kayser, & G. Bodenmann (Eds.), Couples coping with stress: Emerging
      perspectives on dyadic coping (pp.13-32). American Psychological Association:
      Washington, D.C.] and Bodenmann [Bodenmann, G. (1995). A systemic-transactional
      conceptualization of stress and coping in couples. Swiss Journal of Psychology,
      54, 34-49.; Bodenmann, G. (2005). Dyadic coping and its significant for marital
      functioning. In T. Revenson, K. Kayser, & G. Bodenmann (Eds.), Couples coping
      with stress: Emerging perspectives on dyadic coping (pp.33-50). American
      Psychological Association: Washington, D.C.]. In this review we: (1) examine the
      various theoretical models of stress, (2) analyze and summarize the typologies
      relating to stress models (internal versus external, major versus minor, acute
      versus chronic), and (3) summarize findings from stress research in couples that
      has practical significance and may inspire clinical work. Future directions in
      research and clincial significance are suggested.

PMID- 19167140
TI  - The influence of institutional characteristics on length of stay for psychiatric
      patients: a national database study in South Korea.
AB  - The institutionalization of psychiatric patients has put a tremendous burden on
      many societies, but few studies have examined the effects of institutional
      characteristics on patient length of stay (LOS). This paper investigated the
      association between institutional characteristics and LOS for 160,517 psychiatric
      patients in South Korea by applying a two-level modeling technique to
      administrative claims databases covering the entire patient population. Patient
      LOS, expressed in terms of days, was analyzed by taking account of institutional
      type, ownership, location, inpatient capacity, staffing, and patient
      demographics. The characteristics of inpatients were used as control variables
      and consisted of gender, age, sub-diagnosis, and the type of national health
      security program. The main findings of this study are: (1) patient LOS was 69%
      longer at psychiatric hospitals than at tertiary-care hospitals; (2) neither
      location nor inpatient capacity was associated with LOS; (3) larger staffs
      reduced LOS; and (4), LOS increased with a higher proportion of male inpatients,
      inpatients > or =65 years old, or inpatients diagnosed with organic or
      schizophrenic disorders, possibly through contextual effects. The results of this
      study suggest that researchers and policy makers could improve their assessment
      of psychiatric patient LOS and its association with health outcome by taking into
      account institutional characteristics and using multi-level analyses.

PMID- 19167141
TI  - 'Workers', 'clients' and the struggle over needs: understanding encounters
      between service providers and injecting drug users in an Australian city.
AB  - A feature of contemporary Western, neo-liberal democracies is the frequent
      interaction between representatives of health and social services and the members
      of stigmatised and 'unruly' populations, such as injecting drug users. Previous
      research on drugs has tended to ignore the power relations and cultural dynamics
      at work in these encounters, and the ways in which they are framed by the wider
      neo-liberal context. Drawing on an ethnography of street-based heroin use in
      Melbourne, Australia's second largest city, I show how the discourses of both
      service providers and injecting drug users draw on wider neo-liberal values of
      independence, autonomy, rationality and responsibility. Service providers
      negotiate a framework of needs interpretation that creates and reproduces
      professional identities, and maintains boundaries between 'workers' and
      'clients'. It also includes tensions around the definition of injecting drug
      users as 'chaotic' (i.e., failed neo-liberal) subjects, and slippage between
      service philosophies that emphasise a social model of health and forms of service
      delivery that emphasise the production of responsibilised subjects. For their
      part, street-based injectors construct an alternative framework of needs
      interpretation that emphasises their self-reliance, autonomy and independence,
      attributes and capacities largely denied them in service-provider discourse. In
      encounters with service providers, street-based injectors respond in various ways
      that include elements of resistance, strategic accommodation and the
      incorporation of therapeutic discourse. I conclude by considering the
      implications of my analysis for the future development of drug policy and
      practice.

PMID- 19167142
TI  - Gender equity and health sector reform in Colombia: mixed state-market model
      yields mixed results.
AB  - In 1993, Colombia carried out a sweeping health reform that sought to
      dramatically increase health insurance coverage and reduce state involvement in
      health provision by creating a unitary state-supervised health system in which
      private entities are the main insurers and health service providers. Using a
      quantitative comparison of household survey data and an analysis of the content
      of the reforms, we evaluate the effects of Colombia's health reforms on gender
      equity. We find that several aspects of these reforms hold promise for greater
      gender equity, such as the resulting increase in women's health insurance
      coverage. However, the reforms have not achieved gender equity due to the
      persistence of fees which discriminate against women and the introduction of a
      two-tier health system in which women heads of household and the poor are
      concentrated in a lower quality health system.

PMID- 19167143
TI  - Barriers to clinical research participation in a diabetes randomized clinical
      trial.
AB  - Little is known about how barriers to research participation are perceived,
      affected by or interact with patient characteristics, or how they vary over the
      course of a clinical trial. Participants (285) in the Renin-Angiotensin System
      Study (RASS), a randomized clinical primary prevention study of diabetic
      nephropathy and retinopathy at 2 Canadian and 1 US university, rated potential
      barriers to research participation yearly for 5 years. Baseline barriers rated as
      most adversely affecting participation were: missing work; frequency of
      appointments and procedures; study length; number of appointments and procedures;
      access to study location; and physical discomfort associated with procedures.
      Inadequate social support, unstable job, and the use of alcohol and drugs were
      cited relatively infrequently, suggesting that although they may be important,
      candidates for whom these might be issues likely self-selected out of the study.
      Gender and gender by age interactions were found for specific perceived barriers,
      such as work and child care, and baseline barriers correlated with adherence.
      Elucidating the natural history of barriers to research participation is a step
      toward identifying strategies for helping participants overcome them, and
      ultimately may enhance the conduct of research.

PMID- 19167144
TI  - Peer-group support intervention improves the psychosocial well-being of AIDS
      orphans: cluster randomized trial.
AB  - Accumulating evidence suggests that AIDS orphanhood status is accompanied by
      increased levels of psychological distress such as anxiety, depression, intense
      guilt, shame, and anger. However, few studies have examined the possible
      reduction of psychological distress in AIDS orphans through the help of
      interventions that promote well-being. The objective of the study was to evaluate
      the effects of a school-based peer-group support intervention combined with
      periodic somatic health assessments and treatment on the psychosocial well-being
      of AIDS orphans in the Mbarara District of southwestern Uganda. In a cluster
      randomized controlled design, 326 AIDS orphans aged 10-15 years were assigned to
      either peer-group support intervention combined with monthly somatic healthcare
      (n=159) or control group (n=167) for follow-up assessment. Baseline and 10 week
      follow-up psychological assessments were conducted in both groups using self
      administered Beck Youth Inventories. Complete data were available for 298
      orphans. After adjusting for baseline scores, follow-up scores for the
      intervention group in comparison with controls showed significant improvement in
      depression, anger, and anxiety but not for self-concept. This study demonstrated
      that peer-group support intervention decreased psychological distress,
      particularly symptoms of depression, anxiety and anger. Thus, the use of peer
      group support interventions should be incorporated into existing school health
      programs.

PMID- 19167145
TI  - Approximate quantification in young, healthy older adults', and Alzheimer
      patients.
AB  - Forty young adults, 40 healthy older adults, and 39 probable AD patients were
      asked to estimate small (e.g., 25) and large (e.g., 60) collections of dots in a
      choice condition and in two no-choice conditions. Participants could choose
      between benchmark and anchoring strategies on each collection of dots in the
      choice condition and were required to use either benchmark or anchoring on all
      configurations in the no-choice conditions (one per strategy). The benchmark
      strategy involves visual estimation processes whereas the anchoring strategy
      involves both enumeration and estimation processes. Results showed that strategy
      use was influenced by collection, participant, and strategy characteristics. Age
      related and dementia-related differences were found in both strategy use and
      strategy execution. The findings have implications for our understanding of aging
      effects in approximate quantification, strategic variations in Alzheimer's
      patients, and sources of cognitive decline during early stages of Alzheimer's
      disease.

PMID- 19167146
TI  - Effect acidic and alkaline/heat treatments on the bond strength of different
      luting cements to commercially pure titanium.
AB  - OBJECTIVE: The purpose of this study was to characterize the effects of either
      acidic or combined alkaline/heat treatments on the surface of grit-blasted
      commercially pure (cp) titanium. The effects of the previous treatments on the
      shear bond strength (SBS) of cp titanium to conventional glass ionomer, resin
      reinforced glass ionomer and self-adhesive resin luting cements were evaluated.
      METHODS: Titanium discs were machined and received one of the following
      treatments; grit-blasting (GB), grit-blasting followed either by etching in
      HNO(3)/HF solution (GB/Ac) or by combined 5M NaOH treatment/heat treatment at 600
      degrees C for 1h, then immersed for 24h in SBF solution before cementation
      (GB/Ak). The treated surfaces were characterized by atomic force microscope
      (AFM), scanning electron microscope (SEM) and laser-induced brake-down
      spectroscopy (LIBS). Discs were cemented either by Fuji I, Fuji Plus or Rely X
      Unicem luting cements. The SBS was evaluated and the debonded discs were
      investigated by SEM. RESULTS: Two prominent results were revealed; first, GB/Ak
      treatment showed the highest SBS than the other treatments (P<0.0001). Second,
      Rely X Unicem showed the highest SBS than the other cements (P<0.0001). Fuji I
      and Fuji Plus showed predominant cohesive type of failure, whereas Rely X showed
      predominant adhesive type of failure. SIGNIFICANCE: Combined alkaline/heat
      treatments of commercially pure titanium surface shows to be of beneficial effect
      in enhancing SBS to glass ionomer, resin-modified glass ionomer and adhesive
      resin luting cements.

PMID- 19167147
TI  - Reperfusion rate and inhospital mortality of patients with ST segment elevation
      myocardial infarction diagnosed already in the prehospital phase: results of the
      German Prehospital Myocardial Infarction Registry (PREMIR).
AB  - AIMS: We sought to evaluate the in-hospital fate of patients with ST segment
      elevation myocardial infarction (STEMI) diagnosed already in the prehospital
      phase by physican equipped ambulances. METHODS: A total of 2326 consecutive STEMI
      patients were included in PREMIR. For this analysis 218 patients with prehospital
      cardiopulmonary resuscitation were excluded. RESULTS: The median time between
      symptom onset and 12-lead ECG was 85 min. The median time intervals between the
      diagnostic 12-lead ECG and prehospital fibrinolysis were 10 min, until inhospital
      fibrinolysis 52 min and until primar PCI 86min, respectively. Reperfusion therapy
      with prehospital fibrinolysis (24%), inhospital fibrinolysis (13%) or primary PCI
      (45%) was performed in 82% of the patients. Inhospital mortality was 6.0% in
      patients with prehospital fibrinolysis (n = 504), 5.8% in patients with
      inhospital fibrinolysis (n = 278), 4.5% in patients with primary percutaneous
      coronary intervention (n = 962) and 16.2% in patients without early reperfusion
      therapy (n = 377), respectively. In the multivariate propensity score analysis
      comparing prehospital fibrinolysis and primary PCI we observed no significant
      difference in the odds for in-hospital mortality (odds ratio: 1.57, 95% CI: 0.94
      2.63). The final discharge diagnosis was STEMI in 90% of the patients, in
      patients with prehospital fibrinolysis 95%. CONCLUSIONS: In patients with STEMI
      already diagnosed in the prehospital phase the ischemic time is short, accuracy
      of the diagnosis is high and reperfusion therapy is performed in over 82%.
      Inhospital mortality was not different between prehospital fibrinolysis and
      primary PCI.

PMID- 19167148
TI  - Effect of implementation of new resuscitation guidelines on quality of
      cardiopulmonary resuscitation and survival.
AB  - BACKGROUND: During cardiopulmonary resuscitation (CPR), advanced life support
      (ALS) providers have been shown to deliver inadequate CPR with long intervals
      without chest compressions. Several changes made to the 2005 CPR Guidelines were
      intended to reduce unnecessary interruptions. We have evaluated if quality of CPR
      performed by the Oslo Emergency Medical System (EMS) improved after
      implementation of the modified 2005 CPR Guidelines, and if any such improvement
      would result in increased survival. MATERIALS AND METHODS: Retrospective,
      observational study of all consecutive adult cardiac arrest patients treated
      during a 2-year period before (May 2003-April 2005), and after (January 2006
      December 2007) implementation of the modified 2005 CPR Guidelines. CPR quality
      was assessed from continuous electronic recordings from LIFEPACK 12
      defibrillators where ventilations and chest compressions were identified from
      transthoracic impedance changes. Ambulance run sheets, Utstein forms and hospital
      records were collected and outcome evaluated. RESULTS: Resuscitation was
      attempted in 435 patients before and 481 patients after implementation of the
      modified 2005 CPR Guidelines. ECGs usable for CPR quality evaluation were
      obtained in 64% and 76% of the cases, respectively. Pre-shock pauses decreased
      from median (interquartile range) 17s (11, 22) to 5s (2, 17) (p=0.000), overall
      hands-off ratios from 0.23+/-0.13 to 0.14+/-0.09 (p=0.000), compression rates
      from 120+/-9 to 115+/-10 (p=0.000) and ventilation rates from 12+/-4 to 10+/-4
      (p=0.000). Overall survival to hospital discharge was 11% and 13% (p=0.287),
      respectively. CONCLUSION: Quality of CPR improved after implementation of the
      modified 2005 Guidelines with only a weak trend towards improved survival to
      hospital discharge.

PMID- 19167149
TI  - Equilibrium unfolding of the retinoid X receptor ligand binding domain and
      characterization of an unfolding intermediate.
AB  - The retinoid X receptor (RXR) is a ligand-activated transcription factor that
      plays an important role in growth and development and the maintenance of cellular
      homeostasis. A thermodynamic ultraviolet circular dichroism, tryptophan
      fluorescence and ligand binding activity with guanidine as a chemical denaturant
      are consistent with a two step mechanism. The dimeric LBD equilibrates with a
      monomeric intermediate (DeltaG(0)(H(2)O) equal to 8.3 kcal/mol) that is in
      equilibrium with the unfolded state (DeltaG(0)(H(2)O) equal to 2.8 kcal/mol). The
      intermediate was characterized by analytical ultracentrifugation, spectroscopy,
      and collisional fluorescence quenching, which imply that the monomeric
      intermediate maintains a high degree, but not all, of native secondary structure.
      Although intrinsic fluorescence from native and intermediate suggests little
      change in tryptophan environments, fluorescence intensities from fluorescein
      reporter groups differ significantly between the two structures. Analysis of the
      collisional quenching results imply that the intermediate is characterized by
      tryptophans with increased accessibility to small solutes and less overall
      compactness than the native protein.

PMID- 19167150
TI  - Uncertainty characterization approaches for risk assessment of DBPs in drinking
      water: a review.
AB  - The management of risk from disinfection by-products (DBPs) in drinking water has
      become a critical issue over the last three decades. The areas of concern for
      risk management studies include (i) human health risk from DBPs, (ii)
      disinfection performance, (iii) technical feasibility (maintenance, management
      and operation) of treatment and disinfection approaches, and (iv) cost. Human
      health risk assessment is typically considered to be the most important phase of
      the risk-based decision-making or risk management studies. The factors associated
      with health risk assessment and other attributes are generally prone to
      considerable uncertainty. Probabilistic and non-probabilistic approaches have
      both been employed to characterize uncertainties associated with risk assessment.
      The probabilistic approaches include sampling-based methods (typically Monte
      Carlo simulation and stratified sampling) and asymptotic (approximate)
      reliability analysis (first- and second-order reliability methods). Non
      probabilistic approaches include interval analysis, fuzzy set theory and
      possibility theory. However, it is generally accepted that no single method is
      suitable for the entire spectrum of problems encountered in uncertainty analyses
      for risk assessment. Each method has its own set of advantages and limitations.
      In this paper, the feasibility and limitations of different uncertainty analysis
      approaches are outlined for risk management studies of drinking water supply
      systems. The findings assist in the selection of suitable approaches for
      uncertainty analysis in risk management studies associated with DBPs and human
      health risk.

PMID- 19167151
TI  - Editorial comment on: Smooth-muscle-specific gene transfer with the human maxi-K
      channel improves erectile function and enhances sexual behavior in
      atherosclerotic cynomolgus monkeys.

PMID- 19167152
TI  - Smooth-muscle-specific gene transfer with the human maxi-k channel improves
      erectile function and enhances sexual behavior in atherosclerotic cynomolgus
      monkeys.
AB  - BACKGROUND: Despite the advent of effective oral therapies for erectile
      dysfunction (ED), many patients are not successfully treated, and side effects
      have been documented. OBJECTIVE: To further evaluate the potential utility of
      naked DNA-based gene transfer as an attractive treatment option for ED. DESIGN,
      SETTING AND PARTICIPANTS: The effects of gene transfer on erectile function and
      sexual behavior were evaluated in eight male cynomolgus monkeys with ED secondary
      to moderately severe, diet-induced atherosclerosis. INTERVENTION: Following
      establishment of baseline characteristics, animals were subjected to
      intracavernous injection of a smooth-muscle-specific gene transfer vector (pSMAA
      hSlo) encoding the pore-forming subunit of the human large-conductance, calcium
      sensitive potassium channel (Maxi-K). MEASUREMENTS: For the sexual behavior
      studies, 2 wk of baseline data were obtained, and then animals were placed in the
      presence of estrogen-implanted females (n=2) three times per week for 30 min, and
      sexual behavior was recorded. The intracavernous pressure response to papaverine
      injection was also monitored. RESULTS AND LIMITATIONS: Dramatic changes in
      erectile function and sexual behavior were observed after intracorporal gene
      transfer. The frequency of partial (6+/-2 to 10+/-2) and full (2+/-1.5 to 5+/
      1.4) erections were significantly increased, with a parallel 2-3-fold increase in
      the duration of the observed erections. The frequency and latency of ejaculation
      were increased and decreased, respectively. Frequency and duration of grooming by
      the female were increased, and the latency decreased. Increased latency and
      decreased frequency of body contact was also observed, and this is characteristic
      of the typical drop in consort intimacy that occurs after mating in most macaque
      species. In addition, an increased responsiveness to intracavernous papaverine
      injection was observed. CONCLUSIONS: The data indicate that intracorporal Maxi-K
      channel gene transfer enhances erectile capacity and sexual behavior; the data
      imply that increased erectile function per se may lead to increased sexual
      function.

PMID- 19167153
TI  - How to improve the ability to detect pelvic lymph node metastases of urologic
      malignancies.

PMID- 19167154
TI  - Naphthalene degradation by Pseudomonas sp. HOB1: in vitro studies and assessment
      of naphthalene degradation efficiency in simulated microcosms.
AB  - Naphthalene, being a ubiquitous pollutant of the environment and a perilous
      material, its biodegradation has been receiving constant scientific
      consideration. Highly potential, naphthalene degrading bacteria were isolated
      from sediments of polluted Amlakadi canal, Gujarat, India. Among the isolates,
      Pseudomonas sp. HOB1, showed ability to degrade 2000 ppm naphthalene within 24h.
      The culture exhibited potential to tolerate as high as 60,000 ppm of naphthalene.
      Statistical approach was used to analyze the effect of physiological parameters
      and initial biomass concentration on naphthalene degradation. Naphthalene
      degradation was found to be augmented in the pH range of 7.5-8.5. Naphthalene
      degradation was maximum in the temperature range of 35-37 degrees C and initial
      inoculum size of more than 1.8 ml of 1.0 A(660). Simulated microcosm studies in
      the presence and absence of indigenous microflora confirmed its ability for
      naphthalene degradation and to colonize the soil. Pseudomonas sp. HOB1 was found
      to be highly potent in degrading higher concentrations of naphthalene under
      laboratory conditions as well as in simulated microcosms.

PMID- 19167155
TI  - Sensitive adsorptive stripping voltammetric method for determination of lead in
      water using multivariate analysis for optimization.
AB  - A sensitive adsorptive cathodic stripping voltammetric (AdCSV) method is
      presented for direct determination of Pb(II) at nanomolar levels in water based
      on metal complexation with 2-acetylpyridine salicyloylhydrazone (2-APSH) and
      subsequent adsorptive deposition onto hanging mercury drop electrode (HMDE). The
      instrumental and chemical factors were optimized using exploratory (Plackett
      Burman) and sequential (Simplex) designs. Under optimal conditions (pH 5.6, 
      0.552 V for deposition voltage, 0.0083 V for voltage step and 0.87 s for time
      interval for voltage step) a limit of detection of 0.17 nM was obtained and the
      relative standard deviation of five measurements of 17.3 nM was 1.20%. The
      voltammetric responses increased linearly with metal ion concentrations ranging
      from 2.4 to 145 nM. The method was free from interferences of inorganic salts and
      trace metals usually present in seawater. The proposed method was successfully
      validated using certified reference estuarine water (LGC 6016) with relative
      error of -2.15% and applied to real seawater samples (relative errors of -4.40%
      and +1.84%).

PMID- 19167156
TI  - Physicochemical characterization of raw materials and co-products from the
      titanium dioxide industry.
AB  - The present study was conducted to characterize several raw materials and co
      products from the titanium dioxide industry in relation to their elemental
      composition (major, minor and trace elements), granulometry, mineralogy,
      microscopic morphology and physical composition. The main objective was to gain
      basic information for the future potential application of these co-products in
      fields such as agriculture, construction, civil engineering, etc. Microscopic
      studies were performed by applying scanning electron microscopy with X-ray
      microanalysis (SEM-XRMA) while the mineralogical compositions were analysed by
      means of the X-ray diffraction (XRD) technique. The concentrations of major
      elements such as Na, Al, Si, Ca, Ti, Fe, S and K were determined by X-ray
      fluorescence (XRF), while heavy metals and other trace elements were determined
      by ICP-MS. The physicochemical characterization of the raw materials used in the
      titanium dioxide industry, in addition to the characterization of the co-products
      generated, has enabled the evaluation of the degree of fractionation of different
      elements and compounds between the different co-products, as well as the control
      of the possible variations in the physicochemical composition of the raw
      materials throughout the time and the study of the influence of these variations
      in the characteristics of the obtained co-products. As a main conclusion of our
      study, it is possible to indicate that the levels of the pollutant elements
      associated to the co-products analysed were, in general, within safe limits and,
      therefore, they could potentially be used in composites as fertilizers or for
      building materials in road construction, etc. Nevertheless, for the specific
      application of each of these co-products in agriculture, construction and civil
      engineering, additional studies need to be performed to evaluate their
      appropriateness for the proposed application, together with specific studies on
      their health and environmental impact.

PMID- 19167157
TI  - Acetylene soot reaction with NO in the presence of CO.
AB  - The heterogeneous reaction of soot with NO can be considered as a means of
      reduction of the emissions of both pollutants from combustion systems. In this
      paper, the influence of the presence of CO in the soot-NO reaction is studied.
      Soot was obtained by pyrolysis at 1373 K of 5000 ppmv acetylene in nitrogen. The
      study of the influence of CO on the soot-NO reaction was performed in experiments
      fixing NO concentration at 900 ppmv and introducing different CO concentrations
      among 0 and 9900 ppmv. An increase in both the carbon consumption rate and NO
      reduction by acetylene soot was observed as the concentration of CO increases.
      These results can be explained by the oxide-stripping reaction, CO+C(f)(O)-
      >CO(2)+C(f). The direct reaction of CO with NO catalyzed by the carbon surface,
      CO+NO-->CO(2)+1/2N(2) may not be considered in this case the dominant process due
      to the absence of mineral impurities in the acetylene soot. The influence of CO
      in the acetylene soot-NO reaction was also tested in the presence of oxygen (250
      5000 ppmv). In these conditions and for relatively high CO/O(2) ratios, CO seems
      to also contribute to NO reduction by the previous oxide-stripping reaction.

PMID- 19167158
TI  - Photocatalytic degradation of indole in a circulating upflow reactor by UV/TiO2
      process--influence of some operating parameters.
AB  - The present work involves the photocatalytic degradation of indole on a
      recirculating reactor. The effects of various factors as initial concentration of
      indole, catalyst-loading, pH, agitation and flow rate of the solution on the
      photodegradation were examined. The experimental results indicate that the
      optimal pH for indole elimination is about 6-7; the effect of catalyst loading
      shows an optimal value (1g/L) which is necessary to degrade indole; the increase
      of recirculating rate leads to a decrease of degradation rate due to the
      reduction of the residence time; the agitation speed has a slight influence on
      the indole degradation by improving the mass transfer step. Finally, L-H model
      was used to fit experimental results concerning the influence of experimental
      data. L-H model constants' were determined also.

PMID- 19167159
TI  - Experimental study on melting and flowing behavior of thermoplastics combustion
      based on a new setup with a T-shape trough.
AB  - The objective of this work is to quantitatively study the burning characteristics
      of thermoplastics. A new experimental setup with a T-shape trough is designed.
      Based on this setup, the loop mechanism between the wall fire and pool fires
      induced by the melting and dripping of thermoplastic can be well simulated and
      studied. Additionally, the flowing characteristics of pool fires can also be
      quantitatively analyzed. Experiments are conducted for PP and PE sheets with
      different thicknesses. The maximum distances of the induced flowing pool flame in
      the T-shape trough are recorded and analyzed. The typical fire parameters, such
      as heat release rates (HRRs), CO concentrations are also monitored. The results
      show that the softening and clinging of the thermoplastic sheets plays a
      considerable role for their vertical wall burning. It is illustrated that the
      clinging of burning thermoplastic sheet may be mainly related with the softening
      temperatures and the ignition temperatures of the thermoplastics, as well as
      their viscosity coefficients. Through comparing the maximum distances of flowing
      flame of induced pool fires in the T-shape trough for thermoplastic sheets with
      different thicknesses, it is indicated that the pool fires induced by PE
      materials are easier to flow away than that of PP materials. Therefore, PE
      materials may be more dangerous for their faster pool fire spread on the floor.
      These experimental results preliminarily illustrate that this new experimental
      setup is helpful for quantitatively studying the special burning feature of
      thermoplastics although further modifications is needed for this setup in the
      future.

PMID- 19167160
TI  - As(V) adsorption on maghemite nanoparticles.
AB  - In this study a novel adsorbent, maghemite nanoparticles (gamma-Fe(2)O(3)), is
      used for As(V) removal. Maghemite nanoparticles are an exceptional adsorbent
      material due to its magnetic properties and a good adsorption capacity. The aims
      of the study were to investigate the suitability of maghemite nanoparticles for
      As(V) adsorption and to compare properties of different maghemites and their
      As(V) adsorption efficiency. Maghemite nanoparticles were characterized by XRD,
      XPS, TEM, VSM, BET and Zeta potential analyzers. Size of the particles varied
      from 3.8 to 18.4 nm. Adsorption experiments were carried out with three different
      kinds of maghemite nanoparticles: (i) commercially available, (ii) homemade with
      mechanochemical method and (iii) homemade with sol-gel process. All three
      different kinds of maghemite nanoparticles were successful in removing As(V) from
      water, one of them reached as high adsorption capacity as 50mg/g.

PMID- 19167161
TI  - Behaviour of antimony during thermal treatment of Sb-rich halogenated waste.
AB  - Antimony compounds have a wide range of industrial applications, particularly as
      additives in flame retardants. To ensure environmentally friendly waste
      incineration of Sb-rich wastes, it is essential to strengthen the knowledge about
      the fate of antimony and the potential formation of harmful species.
      Investigations should be conducted particularly in relation with the main
      operational parameters controlling the process, chiefly temperature, residence
      time and air supply in the oven and in the post-combustion zone, prior final
      adapted cleaning of the flue-gas stream. Experimental studies focusing on
      antimony behaviour were undertaken through laboratory-scale thermal treatment at
      850 degrees C and 1100 degrees C of a Sb-rich halogenated waste, originating from
      the sector of flame retardants formulation. The configuration of our laboratory
      experimental device allowed to achieve only low oxidative conditions in the waste
      bed, but high oxidative strength coupled with high temperature and sufficient gas
      residence time in the post-combustion zone, as prescribed during the incineration
      of hazardous wastes. Atomic absorption spectroscopy was used to assess the
      partition of antimony in the different compartments of the process. The oxidation
      degree of antimony in the gas-phase was determined by the use of electrochemical
      techniques, namely polarography coupled with anodic stripping voltamperometry.
      The partition of antimony between the residual ash and the gas-phase under
      moderate oxidative conditions in the waste bed was constant, whatever the
      temperature: the volatilization rate for antimony was approximately 64%, while a
      approximately 36% fraction remained in the residual bottom ashes. But
      interestingly, while at 850 degrees C, antimony was mainly present in the gas
      phase at a +III oxidation degree, an increase in temperature of 250 degrees C
      favoured the presence of antimony to its highest oxidation degree +V in the flue
      gas stream, a valence known to be involved in less toxic species.

PMID- 19167162
TI  - Removal of Pb(II) ions from aqueous solution by a waste mud from copper mine
      industry: equilibrium, kinetic and thermodynamic study.
AB  - The objective of this study was to assess the adsorption potential of a waste mud
      (WM) for the removal of lead (Pb(II)) ions from aqueous solutions. The WM was
      activated with NaOH in order to increase its adsorption capacity. Adsorption
      studies were conducted in a batch system as a function of solution pH, contact
      time, initial Pb(II) concentration, activated-waste mud (a-WM) concentration,
      temperature, etc. Optimum pH was specified as 4.0. The adsorption kinetic studies
      indicated that the overall adsorption process was best described by pseudo-second
      order kinetics. The equilibrium adsorption capacity of a-WM was obtained by using
      Langmuir and Freundlich isotherm models and both models fitted well. Adsorption
      capacity for Pb(II) was found to be 24.4 mg g(-1) for 10 g L(-1) of a-WM
      concentration. Thermodynamic parameters including the Gibbs free energy (Delta G
      degrees), enthalpy (Delta H degrees), and entropy (DeltaS degrees) indicated that
      the adsorption of Pb(II) ions on the a-WM was feasible, spontaneous and
      endothermic, at temperature range of 0-40 degrees C. Desorption studies were
      carried out successfully with diluted HCl solutions. The results indicate that a
      WM can be used as an effective and no-cost adsorbent for the treatment of
      industrial wastewaters contaminated with Pb(II) ions.

PMID- 19167163
TI  - Influence of minerals on lead-induced alterations in liver function in rats
      exposed to long-term lead exposure.
AB  - The objective of this study was to evaluate the role of minerals on lead-induced
      effect on the liver. Differentiation of minerals and heavy metals pose an
      inherent problem due to certain common properties shared by them. With this
      approach to the problem of heavy metal toxicity, in the present study two groups
      of male Wistar albino rats, one group (well-nourished) fed on mineral rich diet
      and other group (undernourished) fed on diet without mineral supplements were
      used. Both the groups of rats were subjected to long-term lead exposure. The diet
      of well-nourished group was supplemented with calcium (Ca); 1.2%, phosphorous
      (P); 0.6%, iron (Fe); 90 mg/kg, zinc (Zn); 50mg/kg, magnesium (Mg); 0.08%,
      manganese (Mn); 70 mg/kg, selenium (Se); 0.2mg/kg, copper (Cu); 5mg/kg,
      molybdenum (Mo); 0.8 mg/kg, iodine (I); 0.6 mg/kg, cobalt (Co); 3.0mg/kg. Their
      blood lead and parameters of liver function were monitored periodically. Results
      of the study showed a very high statistically significant increase (p<0.001) in
      the blood lead (PbB) levels and liver function test parameters in the
      undernourished subjects compared to the well-nourished subjects. Nutritional
      management of lead poisoning is of importance since essential elements and toxic
      heavy metals may interact to minimize the absorption of lead.

PMID- 19167164
TI  - Toxicity of free and various aminocarboxylic ligands sequestered copper(II) ions
      to Escherichia coli.
AB  - Cytotoxicity of free Cu(II) ions and its complexes of EDTA, NTA or IDA in
      Escherichia coli (AB 4401) wild type cells were assessed by cell inactivation
      assay. In order to understand the toxic effects of these additives, membrane
      status by AFM vis-a-vis K(+) ion efflux were followed in the absence and in the
      presence of Cu(II) ions or its complexes. This was coupled with the
      determinations of cellular copper concentrations by atomic absorption
      spectrometry. The observed results show that free copper ions are more cytotoxic
      and cause considerable plasma membrane damage compared to that of Cu-EDTA, Cu-NTA
      and Cu-IDA. Determination of cellular copper reveals that Cu(2+) and Cu-NTA are
      able to enter inside the cells while Cu-EDTA and Cu-IDA fail to do that. This may
      be attributed to the electron affinity of free Cu(2+) ions and Cu-NTA, which help
      in binding with histidine present in copper transport proteins. In addition to
      cytotoxicity, genotoxicity of free copper and its complexes were also assessed on
      E. coli isogenic DNA repair proficient and repair-deficient strains. In contrast
      to free Cu(2+) ions, Cu-NTA does not cause any significant cytotoxicity but
      render greater genotoxicity.

PMID- 19167165
TI  - Trichinella zimbabwensis in wild Nile crocodiles (Crocodylus niloticus) of South
      Africa.
AB  - Recent discovery of Trichinella zimbabwensis in crocodiles from Zimbabwe, Lake
      Cahora Basa, Mozambique, and from lake Abaja, Ethiopia, prompted strict control
      measures to curb the possible spread of the infection to humans and also to
      prevent its introduction to other countries, which were considered free of this
      pathogen. In 2006, the Chief Directorate Veterinary Services of Mpumalanga
      Province of South Africa launched a survey to investigate the status of wild and
      commercial breeding crocodiles in the province. To evaluate if T. zimbabwensis
      was circulating in the environments where crocodiles are living in South Africa,
      9 fish, 36 reptiles (including 27 Nile crocodiles) and 4 mammals have been
      investigated to detect Trichinella sp. larvae in their muscles. In January 2008,
      a Nile crocodile from Komatipoort, sampled by means of a tail biopsy, tested
      positive for Trichinella larvae. In June-July 2008, Trichinella sp. larvae were
      also detected in four other Nile crocodiles from the Olifants River Gorge. The
      prevalence of Trichinella infection in the investigated wild Nile crocodiles from
      South Africa is 38.5%. The larvae were identified as belonging to T. zimbabwensis
      by multiplex-PCR. These are the first reports of T. zimbabwensis in South Africa
      and suggest that the distribution area of this parasite species is wider than
      that believed in the past.

PMID- 19167166
TI  - Antibody and inflammatory responses in laying hens with experimental primary
      infections of Ascaridia galli.
AB  - Ascaridia galli, an intestinal nematode that affects hens and other domestic and
      wild birds, causes economic losses in avian exploitations. The present work shows
      that A. galli stimulates a strong antibody response as well as an intense
      inflammatory reaction, in the intestinal mucous of experimentally infected
      Lohmann Brown laying hens. IgG antibodies against soluble extracts of A. galli
      embrionated eggs and adult worms, were detected in both blood and yolks eggs from
      infected hens during a period of 105 days after the infection. This indicates
      that hens transfer to their offspring a part of the IgG antibodies produced when
      they become infected. The antigens responsible for the stimulation of specific
      IgG were molecules of 30-34, 44-54 and 58-90 kDa, while in the yolk eggs of
      infected hens a reactivity directed against antigens of molecular weight (M(w))
      lower than 50 kDa was detected. Histology revealed traumatic lesions with
      leukocyte infiltration, and inflammation of the intestinal wall of the infected
      hens after 105 days of initial infection. The possible influence of the immune
      and inflammatory response on the population dynamics of the parasite is
      discussed.

PMID- 19167167
TI  - Cortisol response to inoculation in 4-year-old children.
AB  - This study examined whether there was a cortisol response to inoculation or if
      pre-inoculation levels were already elevated due to an anticipatory response to
      going to the doctors' office. For 4-year-old children, a base saliva sample was
      obtained in the home on a non-stress day, and a pre-inoculation saliva sample was
      obtained in the doctors' office prior to the stress. Doctors' office pre
      inoculation cortisol was higher than home-based cortisol, suggesting the
      occurrence of an anticipatory cortisol response to the impending stress. Post
      inoculation cortisol levels (+20 min) were comparable to home-based cortisol,
      indicating that there was no cortisol response to the inoculation itself. While
      there was no mean increase in cortisol, individual differences in cortisol
      response existed. Cortisol increases were related to important aspects of child
      behavioral functioning, including internalizing and externalizing behavior
      ratings.

PMID- 19167168
TI  - Maternal deprivation by early weaning increases corticosterone and decreases
      hippocampal BDNF and neurogenesis in mice.
AB  - We previously demonstrated that early weaning increases anxiety and
      neuroendocrine stress responses in rats and mice. In addition, early-weaned mice
      show precocious myelin formation, especially in the amygdala, suggesting that
      these mice are vulnerable to psychological stress. In the present experiments, we
      examined corticosterone response after early weaning and how early weaning
      affects hippocampal neurotrophic factor and neurogenesis, which have been linked
      to depressive behavior in human and animals models. When the mice were weaned at
      PD14, both male and female mice showed higher corticosterone levels up to 48h
      after weaning. In contrast, after standard weaning, corticosterone levels
      returned to the baseline within 2h. Early-weaned males, but not females, had less
      brain-derived neurotrophic factor (BDNF) protein in the hippocampus at 3 weeks of
      age than standard-weaned mice. Neural stem cells were labeled with
      bromodeoxyuridine (BrdU) injections at 2, 3, or 5 weeks of age, and assayed at 3,
      5, and 8 weeks of age, respectively. Early-weaned males had fewer BrdU
      immunoreactive cells in the dentate gyrus at 3, 5, and 8 weeks. In early-weaned
      females, fewer BrdU-positive cells were observed only at 5 weeks. Double-staining
      with BrdU and the neuron markers NeuN and Tuj1 demonstrated that neurogenesis was
      lower in early-weaned mice at 5 weeks of age. These results suggest that lack of
      mother-infant interaction during the late lactation period leads to an increase
      in corticosterone synthesis for 2 days and a decrease in BDNF synthesis in males;
      moreover, this lack of interaction transiently inhibits hippocampal cell
      proliferation and survival in both males and females, although the effects were
      more pronounced in males.

PMID- 19167169
TI  - Depressive symptoms, gender, and growth in cigarette smoking among indigenous
      adolescents.
AB  - This study reports findings from two-level growth curve modeling of cigarette
      smoking and depressive symptoms based on the first three waves of data from a
      longitudinal study of Indigenous adolescents and their parents/caretakers in the
      northern Midwest and Canada. The 743 adolescents were aged 10-13 years at Wave 1
      and 12-15 years at Wave 3. Over the three years of the study the overall
      retention rate was 93%. By Wave 3, 39% of the adolescent girls and 25% of the
      boys had smoked cigarettes in the past 12 months. The growth curve results
      indicated that smoking increased for both adolescent boys and girls across time.
      Depressive symptoms were associated with an increase in cigarette smoking for
      girls but not boys.

PMID- 19167170
TI  - Alcohol criteria endorsement and psychiatric and drug use disorders among DUI
      offenders: greater severity among women and multiple offenders.
AB  - PURPOSE: Data from the Collaborative Study on the Genetics of Alcoholism (COGA),
      a high-risk family study of alcohol dependence, were used to examine differences
      in alcohol diagnostic criteria endorsement and psychiatric and drug use disorders
      by gender and by number of DUI offenses. RESULTS: Individuals with two or more
      DUIs exhibited greater severity of alcohol dependence than those with none or one
      DUI. This severity was characterized in three ways: (1) higher endorsement of
      alcohol diagnostic criterion items, with evidence of greater severity among
      women, (2) higher prevalence of co-occurring lifetime psychiatric disorders, and
      (3) higher rates of drug use and of dependence on cocaine, stimulants, and, for
      women only, marijuana and opiates. CONCLUSIONS: By examining gradations of
      disorder within a combination of two high-risk indicators, DUI and family
      vulnerability, this study provides useful information for clinical research about
      individuals with chronic and severe alcohol problems. In addition, the observed
      gender differences in this high-risk sample will contribute to the literature on
      alcohol dependence among women at the more severe end of the dependence spectrum.

PMID- 19167171
TI  - Injecting-related injury and disease among clients of a supervised injecting
      facility.
AB  - BACKGROUND: The process of drug injection may give rise to vascular and soft
      tissue injuries and infections. The social and physical environments in which
      drugs are injected play a significant role in these and other morbidities.
      Supervised injecting facilities (SIFs) seek to address such issues associated
      with public injecting drug use. AIMS: Estimate lifetime prevalence of injecting
      related problems, injury and disease and explore the socio-demographic and
      behavioral characteristics associated with the more serious complications.
      DESIGN, SETTING, PARTICIPANTS: Self-report data from 9552 injecting drug users
      (IDUs) registering to use the Sydney Medically Supervised Injecting Centre
      (MSIC). FINDINGS: Lifetime history of either injecting-related problems (IRP) or
      injecting-related injury and disease (IRID) was reported by 29% of the 9552 IDUs;
      26% (n=2469) reported ever experiencing IRP and 10% (n=972) reported IRID.
      Prevalence of IRP included difficulties finding a vein (18%), prominent scarring
      or bruising (14%) and swelling of hands or feet (7%). Prevalence of IRID included
      abscesses or skin infection (6%), thrombosis (4%), septicaemia (2%) and
      endocarditis (1%). Females, those who mainly injected drugs other than heroin,
      and those who reported a history of drug treatment, drug overdose, and/or sex
      work, were more likely to report lifetime IRID. Frequency and duration of
      injecting, recent public injecting, and sharing of needles and/or syringes were
      also independently associated with IRID. CONCLUSIONS: IRPs and IRIDs were common.
      Findings support the imperative for education and prevention activities to reduce
      the severity and burden of these preventable injecting outcomes. Through
      provision of hygienic environments and advice on venous access, safer injecting
      techniques and wound care, SIFs have the potential to address a number of risk
      factors for IRID.

PMID- 19167172
TI  - The behavioral pain response to heelstick in preterm neonates studied
      longitudinally: description, development, determinants, and components.
AB  - OBJECTIVES: Preterm infants often experience multiple painful procedures during
      their stay in neonatal intensive care units (NICUs). The objectives of this study
      were to evaluate behavioral responses to heelstick in preterm newborns,
      characterize developmental changes and the effects of other demographic and
      clinical variables on the pain response, and estimate the contributions of
      individual Neonatal Infant Pain Scale (NIPS) behaviors to the summary pain score.
      METHODS: A longitudinal study was conducted to evaluate the behavioral responses
      of 35 preterm newborns to multiple heelstick procedures during their stay in the
      NICU. Sixty-one video recordings of blood collection by heel lance were evaluated
      for behavioral pain response using the NIPS. Generalized linear mixed models were
      calculated to address the study objectives. RESULTS: The increases in NIPS scores
      from the baseline to the blood draw were highly significant (mean baseline
      score=3.34, mean blood draw score=5.45, p<0.001). The newborns' pain responses
      increased an average of 0.23 points on the NIPS scale each week (p=0.002). Lower
      NIPS scores during the heelstick procedure were associated with four clinical
      variables: younger post-menstrual age at birth, lower birthweight, mechanical
      ventilation, and longer length of stay in the NICU. Crying, arousal state, and
      facial grimace contributed more than 85% of the increase in NIPS scores during
      the heelstick procedure. DISCUSSION: While behavioral responses to pain are
      attenuated in young, severely ill preterm newborns, they can be reliably
      detected. The most robust pain behaviors are crying, changes in arousal state,
      and facial grimacing.

PMID- 19167173
TI  - Effect of maternal fatness on fetal steroids and semi-quantitative real-time PCR
      expression of receptor genes in sheep.
AB  - Sexual differentiation of the brain occurs between d 30 and 70 in the fetal lamb.
      The objective of this experiment was to determine if maternal fatness affects
      fetal steroid production and expression of their receptors which may ultimately
      alter endocrine systems postnatally. Fetuses were collected from ewes fed at
      either 100% (Control; n=5) or 150% (Fat; n=6) of NRC recommendations from 60 d
      prior to breeding until collection at 75 d of gestation. Hypothalamic and
      amygdala neural tissues were collected from twin male/female fetuses. Serum
      concentrations of testosterone were greater (P<0.001) in male fetuses compared to
      female fetuses. Further, male fetuses from Fat ewes had greater (P<0.05) serum
      concentrations of testosterone than male fetuses from Control ewes, but
      differences in testicular steroidogenic enzyme mRNA were not detected (P=0.18).
      Quantity of hypothalamic mRNA for estrogen receptor (ER) beta tended (P=0.1) to
      be influenced by a sex by treatment interaction. Messenger RNA for ER-beta was
      greater in female fetuses than male fetuses from Control ewes (P=0.05). Although
      amount of ER-beta mRNA did not differ among male fetuses (P=0.7), amounts tended
      to be less (P=0.07) in female fetuses from Fat ewes compared to those from
      Control ewes, and did not differ (P> or =0.8) from male fetuses. Hypothalamic ER
      alpha mRNA tended (P=0.1) to be less in fetuses from Fat ewes compared to Control
      fetuses but was not influenced (P=0.3) by fetal sex or their interaction. Amount
      of mRNA for hypothalamic progesterone receptor tended (P=0.06) to be greater in
      male fetuses than female fetuses and tended to be less (P=0.06) in fetuses from
      Fat ewes than in Control fetuses, but did not differ by any sex by treatment
      interaction (P=0.6). Hypothalamic RNA for the androgen receptor did not differ by
      sex, dam nutritional treatment, or the interaction. Likewise, amygdala RNA for
      the estrogen or androgen receptor did not differ (P> or =0.3) by sex, treatment,
      or their interaction. Dam fatness appears to decrease the expression of
      progesterone receptor, ER-alpha, and decrease amount of ER-beta in the female
      fetuses while increasing circulating concentrations of testosterone in male
      fetuses. Altered expression of hypothalamic receptor genes by the uterine
      environment may affect adult responses to stress, sexual behavior and/or the
      pattern of gonadotropin release in response to gonadal steroids.

PMID- 19167174
TI  - Progestogens and brain: an update.
AB  - Each synthetic progestins has its own specific activities on different tissues,
      which can vary significantly between progestins of different classes and even
      within the same class. Indeed, different progestins may support or oppose the
      effects of estrogen depending on the tissue, thereby supporting the concept that
      the clinical selection of progestins for HRT is critical in determining potential
      positive or detrimental effects. These actions might be particularly relevant in
      the central nervous system (CNS) where progesterone (P) has pivotal roles besides
      reproduction and sexual behavior, going from neuropsychological effects to
      neuroprotective functions. Growing evidence supports the idea that synthetic
      progestins differ significantly in their brain effects, and clinical studies
      indicate that these differences also occur in women. Molecular and cellular
      characterization of the signaling properties of synthetic progestins in brain
      cells is therefore required and is hoped will lead to a better clinical
      utilization of the available compounds, as well as to new concepts in the
      engineering of new molecules. The aim of the present paper is to briefly review
      and compare neuroendocrine effects of progestogens with special reference to P
      metabolism into neuroactive steroids and the opioids system.

PMID- 19167175
TI  - Breast cancer seeding associated with core needle biopsies: a systematic review.
AB  - BACKGROUND: Preoperative diagnosis has become the standard in breast cancer (BC)
      management. Recently, ultrasound guided core needle biopsy (CNB) and stereotactic
      needle core biopsy have replaced fine needle aspiration cytology. Epithelial cell
      displacement (DE) occurs frequently after core needle biopsy (CNB) for breast
      cancer diagnosis. AIM: Systematically review (between 1900 and 2008) the clinical
      significance of DE after CNB in BC patients, and associated risk factors (delay
      between biopsy and surgery, needle passes, duration of the procedure, tumor size,
      histological type, tumor grade, margins, type of surgery, and of adjuvant
      treatment). MATERIALS AND METHODS: We selected 15 studies: 9 assessed the rate of
      DE after CNB and 6 the impact of CNB on outcome endpoints. RESULTS: We found 3
      prospective and 12 retrospective studies. However these had numerous biases such
      as insufficient power, confounding factors, selection of cases and controls,
      surrogate endpoints, heterogeneity of measured displacement. Malignant DE on
      surgical specimens occurred in 22% of the patients. A short interval between CNB
      and surgical excision increased the risk of detecting displaced cells. No
      increase in local recurrence was reported after CNB. Contradictory results were
      found in terms of sentinel node metastases. Only one study evaluated overall
      survival data and reported no worse survival in patients with preoperative CNB.
      CONCLUSION: Although data are limited, no increased morbidity has been associated
      with iatrogenic seeding after CNB.

PMID- 19167176
TI  - Stress, psychological distress, psychosocial factors, menopause symptoms and
      physical health in women.
AB  - OBJECTIVES: Relatively few studies have evaluated relationships between stress,
      psychological distress, psychosocial factors and menopause symptoms, and none
      have evaluated emotional intelligence (EI) in relation to menopause. In this
      study, direct and indirect relationships were evaluated between stress,
      psychological distress, psychosocial factors (e.g. social support, coping, EI),
      menopause symptom severity and physical health in middle-aged women. METHODS: One
      hundred and sixteen women aged 45-55 years were recruited through women's health
      centres and community organizations. They completed a short questionnaire asking
      about stress, psychological distress (i.e. anxiety, depression), EI, attitude to
      menopause, menopause symptoms and physical health. RESULTS: Low emotional
      intelligence was found to be related to worse menopause symptoms and physical
      health, and these associations were partly mediated by high stress, anxiety and
      depression, a negative attitude to menopause and low proactive coping.
      CONCLUSIONS: Women with high EI appear to hold more positive attitudes to
      menopause and experience less severe stress, psychological distress and menopause
      symptoms and better physical health. These results suggest that women who expect
      menopause to be a negative experience or are highly stressed or distressed may be
      more likely to experience a more negative menopause.

PMID- 19167177
TI  - Management of acute malignant colorectal obstruction with a novel self-expanding
      metallic stent as a bridge to surgery.
AB  - PURPOSE: To prospectively evaluate the safety and clinical efficacy of a newly
      designed self-expandable metallic stent (SEMS) in the treatment of patients with
      acute malignant colorectal obstruction. METHODS: Between April 2001 and October
      2007, 52 patients with acute malignant colorectal obstruction were treated with a
      new designed SEMS as an investigational bridge to surgery. Patients were
      prospectively followed and relevant data collection was collected, including
      details regarding technique, clinical symptoms, complications, need for elective
      surgery, and overall survival. RESULTS: Stent placement was technically
      successful in all but two patients (due to complete obstruction) with no
      procedure-related complications. Complications included stent migration (n=4),
      anal pain (n=2) and stool impaction (n=1). Clinical success was achieved in 49
      (98%) of 50 patients with resolution of bowel obstruction within 2 days of stent
      placement. In one patient with stool impaction 2 days after stent placement,
      endoscopic disimpaction was successfully performed. An elective one-stage
      surgical procedure was performed in all 50 patients who successfully received a
      SEMS as a bridge to surgery within a mean of 8+/-2 days (range: 4-11 days) after
      stent placement. Mean follow-up time was 36+/-12 months (range 3-70 months), and
      all patients remained alive at the time of this report. CONCLUSION: The newly
      designed SEMS placement as a bridge to surgery was a safe and effective
      intervention for colonic decompression in patients with acute malignant
      colorectal obstruction and allowed a high proportion of patients to be
      successfully proceeded to elective surgery.

PMID- 19167178
TI  - Impact of right ventricular contrast attenuation on the accuracy of right
      ventricular function analysis at cardiac multi-detector-row CT.
AB  - PURPOSE: To investigate the impact of right ventricle (RV) contrast attenuation
      on the accuracy of RV function analysis at cardiac CT performed for coronary
      imaging. MATERIALS AND METHODS: We analyzed multi-phase cardiac dual-source CT
      studies of 40 consecutive patients (mean age 60.9+/-12.3 years; 13 women) with
      normal valve function. Function analyses of both the right and left ventricle (RV
      and LV) were performed using dedicated post processing software and stroke
      volumes (SV) were computed for each ventricle. The accuracy of the RV-SV
      measurements was determined based upon comparison to LV-SV measurement. The level
      of contrast attenuation of the RV was recorded at three separate regions of
      interest-below the pulmonary valve, mid-ventricular, and inferior RV. The
      accuracy of RV function assessment was correlated with the level of attenuation
      using regression analyses. RESULTS: There was a statistically significant
      correlation between the accuracy of RV function assessment and the level of RV
      attenuation in the inferior RV (adjusted R(2)=73.1%, p<0.0001). When compared to
      LV-SV measurements, in studies with low RV attenuation (<175 HUs, n=19) the mean
      deviation of RV-SV from LV-SV was 29.0+/-10.8 ml (42.1+/-13.9%). In studies with
      high RV attenuation (> or =175 HUs, n=21) the mean deviation of RV-SV from LV-SV
      was significantly lower 6.9+/-10.5 ml (9.9+/-16.0%). CONCLUSION: The accuracy of
      RV function analysis is dependent on the level of contrast medium attenuation
      achieved in the inferior RV. There should be at least intermediate attenuation
      (>175 HUs) to enable accurate functional analysis. At low attenuation levels RV
      function parameters are prone to underestimation.

PMID- 19167179
TI  - Differentiation of adrenal adenomas from nonadenomas using CT histogram analysis
      method: a prospective study.
AB  - OBJECTIVE: The objective of our study was to prospectively evaluate the
      effectiveness of computed tomography (CT) histogram analysis method in the
      differentiation of benign and malignant adrenal masses. MATERIALS AND METHODS:
      Between March 2007 and June 2008, 94 patients (46 males, 48 females, age range:
      30-79 years, mean age: 57.7 years) with 113 adrenal masses (mean diameter: 3.03
      cm, range: 1.07-8.02 cm) were prospectively evaluated. These included 66
      adenomas, 45 metastases and 2 pheochromocytomas. Histogram analysis method was
      performed using a circular region of interest (ROI) and mean attenuation, total
      number of pixels, number of negative pixels and subsequent percentage of negative
      pixels were detected on both unenhanced and delayed contrast-enhanced CT images
      for each adrenal mass. A mean attenuation threshold of 10Hounsfield unit (HU) for
      unenhanced CT and 5% and 10% negative pixel thresholds for both unenhanced and
      delayed contrast-enhanced CT were calculated by a consensus of at least two
      reviewers and the correlation between mean attenuation and percentage of negative
      pixels was determined. Final diagnoses were based on imaging follow-up of minimum
      6 months, biopsy, surgery and adrenal washout study. RESULTS: 51 of 66 adenomas
      (77.3%) showed attenuation values of < or =10HU and 15 (22.7%) adenomas showed
      more than 10HU on unenhanced CT. All of these adenomas contained negative pixels
      on unenhanced CT. Eight of 66 (12.1%) adenomas showed a mean attenuation value of
      < or =10HU on delayed contrast-enhanced scans and 45 adenomas (68.2%) persisted
      on containing negative pixels. All metastases had an attenuation value of greater
      than 10HU on unenhanced CT images. 21 of 45 (46.6%) metastases contained negative
      pixels on unenhanced images but only seven metastases (15.5%) had negative pixels
      on delayed contrast-enhanced images. Two pheochromocytomas had negative pixels on
      both unenhanced and delayed contrast-enhanced CT images. Increase in the
      percentage of negative pixels yielded high correlation with mean attenuation
      decreases, both on unenhanced and delayed contrast-enhanced CT. Our sensitivity
      was 90.9% for the 10% negative pixel percentage threshold compared to 77.2%
      sensitivity for < or =10HU mean attenuation threshold for unenhanced CT. Both
      methods gave a 100% specificity for the diagnosis of adenoma. We also obtained a
      37.9% sensitivity for 5% negative pixel threshold and a slightly lower
      sensitivity of 28.8% for 10% negative pixel threshold compared to the 12.1%
      sensitivity of < or =10HU mean attenuation threshold while maintaining 100%
      specificity for contrast-enhanced CT. CONCLUSION: The CT histogram analysis is a
      simple and easily applicable method which provides higher sensitivity than the
      commonly used 10HU threshold mean attenuation method of unenhanced CT and can
      replace it for the diagnosis of an adenoma. But with contrast-enhanced CT,
      although 100% specificity is being maintained, the sensitivities obtained are
      very poor for each method and is therefore likely to limit CT histogram analysis
      to be used as a clinically useful adjunct in the diagnosis of adenoma.

PMID- 19167180
TI  - Role of CT colonography in inflammatory bowel disease.
AB  - CT colonography (CTC), or virtual colonoscopy, is a non-invasive imaging method
      that uses CT data sets combined with specialized imaging software to examine the
      colon. CTC is not used routinely in patients with inflammatory bowel disease
      (IBD). However, investigating contemporarily the colon, other abdominal organs
      and the peritoneum with CTC is at times useful in patients with IBD, especially
      when other diagnostic tools fail. Furthermore, since symptoms of colorectal
      cancer sometimes superimpose to those of inflammatory disease, it may happen to
      image patients with IBD incidentally. If clinical signs are suggestive for
      inflammatory disease, exam technique should be modified accordingly and
      distinguishing radiological findings searched for.

PMID- 19167182
TI  - A sensitive and rapid liquid chromatography-tandem mass spectrometry method for
      the quantification of the novel neurokinin-1 receptor antagonist aprepitant in
      rhesus macaque plasma, and cerebral spinal fluid, and human plasma with
      application in translational NeuroAIDs research.
AB  - A sensitive and rapid liquid chromatography-tandem mass spectrometry method has
      been developed for to assess therapeutic exposures of aprepitant in HIV-infected
      patients and rhesus macaques. The method utilized a simple sample-preparation
      procedure of protein precipitation with methanol. Chromatographic separation was
      performed on a reversed phase C(8) column (Hypersil Gold, 50 mm x 2.1 mm, 3
      microm) using a mobile phase composed of acetonitrile and water in 0.5% formic
      acid through gradient elution. Electro-spray ionization in positive mode was
      incorporated in the tandem mass spectrometric detection. The lower limit of
      quantitation of aprepitant in plasma of rhesus macaques and human and cerebral
      spinal fluid of rhesus macaques were 1, 1, and 0.1 ng/mL, respectively. The
      method has been successfully employed to measure aprepitant in preclinical and
      clinical samples collected from three SIV-infected rhesus macaques and ten
      patients with HIV infection. In conclusion, this liquid chromatography-tandem
      mass spectrometry method is suitable for preclinical-clinical translational
      research exploring exposure-response relationships with aprepitant as well as
      therapeutic drug monitoring of aprepitant.

PMID- 19167181
TI  - In vivo lipid diffusion coefficient measurements in rat bone marrow.
AB  - The diffusion coefficient of lipids, D(l), within bone marrow, fat deposits and
      metabolically active intracellular lipids in vivo will depend on several factors
      including the precise chemical composition of the lipid distribution (chain
      lengths, degree of unsaturation, etc.) as well as the temperature. As such, D(l)
      may ultimately prove of value in assessing abnormal fatty acid distributions
      linked to diseases such as cystic fibrosis, diabetes and coronary heart disease.
      A sensitive temperature dependence of D(l) may also prove of value for MR-guided
      thermal therapies for bone tumors or disease within other fatty tissues like the
      breast. Measuring diffusion coefficients of high molecular weight lipids in vivo
      is, however, technically difficult for a number of reasons. For instance, due to
      the much lower diffusion coefficients compared to water, much higher b factors
      than those used for central nervous system applications are needed. In addition,
      the pulse sequence design must incorporate, as much as possible, immunity to
      motion, susceptibility and chemical shift effects present whenever body imaging
      is performed. In this work, high b-factor line scan diffusion imaging sequences
      were designed, implemented and tested for D(l) measurement using a 4.7-T
      horizontal bore animal scanner. The gradient set available allowed for b factors
      as high as 0.03 micros/nm(2) (30,000 s/mm(2)) at echo times as short as 42 ms.
      The methods were used to measure lipid diffusion coefficients within the marrow
      of rat paws in vivo, yielding lipid diffusion coefficients approximately two
      orders of magnitude smaller than typical tissue water diffusion coefficients.
      Phantom experiments that demonstrate the sensitivity of lipid diffusion
      coefficients to chain length and temperature were also performed.

PMID- 19167183
TI  - HPLC analysis, semi-preparative HPLC preparation and identification of three
      impurities in salidroside bulk drug.
AB  - Salidroside is a bioactive compound mainly distributed in Rhodiola L.
      (Crassulaceae). It has been widely used in Chinese traditional medicine. In this
      paper, three impurities were found during the analysis of salidroside bulk drug.
      The enrichment of impurities was carried out by ODS column chromatography, using
      methanol-water (13:87, v/v) as eluent and the purification of impurities was
      achieved by semi-preparative HPLC, using methanol-water (11:89, v/v) as mobile
      phase, respectively. Three impurities were characterized as 4-(2-hydroxylethyl)
      phenol-1-O-beta-D-glucopyranoside, 4-hydroxyphenacyl-D-glucopyranoside and p
      acetylphenyl-O-beta-D-glucopyranoside by a variety of spectral data (IR, UV, MS,
      1H NMR, 13C NMR, DEPT and 2D NMR). The simultaneous quantitative determination of
      salidroside and its impurities (Imp. 1, 2 and 3) was performed by reverse-phase
      HPLC method with UV detection. Specificity, linearity, sensitivity, precision and
      accuracy were evaluated.

PMID- 19167184
TI  - [About a neuropathy...].

PMID- 19167185
TI  - [Klinefelter syndrome and acute myeloblastic leukaemia].

PMID- 19167186
TI  - [Hydatid cyst of the lumbar rachis].

PMID- 19167187
TI  - The psychometric properties of the Attention-Distraction, Inhibition-Excitation
      Classroom Assessment Scale (ADIECAS) in a sample of children with moderate and
      severe intellectual disabilities.
AB  - The Attention-Distraction, Inhibition-Excitation Classroom Assessment Scale
      (ADIECAS) [Evans, P. L. C. (1975). Inhibition and stimulus generalization in the
      discrimination learning of ESN(S) and ESN(M) children. Unpublished Ph.D. thesis.
      Manchester, UK: University of Manchester] assesses attention-related difficulties
      in children with intellectual disabilities (ID). The present study explored the
      psychometric properties of the ADIECAS with a sample of 84 children with moderate
      and severe ID whose teachers completed the ADIECAS and the Conners' Teachers
      Rating Scale [Goyette, C. H, Conners, C. K., & Ulrich, R. F. (1978). Normative
      data on revised Conners' parent and teachers rating scales. Journal of Abnormal
      Child Psychology, 6, 221-236]. Following factor analysis the Evans and Hogg
      [Evans, P. L. C., & Hogg, J. (1984). A classroom rating scale for use with
      mentally retarded children. British Journal of Clinical Psychology, 23, 187-194]
      structure was the most appropriate for use with this sample. Moderate to strong
      positive relationships were found between the ADIECAS and the Conners', and the
      ADIECAS factors were significant predictors of the Conners' subscales. This study
      provides further support for the ADIECAS as a reliable and valid measure of ADHD
      related symptoms among children with moderate and severe ID.

PMID- 19167188
TI  - Preoperative antiseptics in clean/contaminated maxillofacial and oral surgery:
      prospective randomized study.
AB  - In order to show the effectiveness of preoperative antiseptic mouthwash the
      authors undertook a prospective study in 120 patients who underwent elective
      surgery under general or local anesthesia. Patients were allocated toone of 4
      groups, depending on whether the oral cavity was washed preoperatively with 1%
      cetrimide, chlorhexidine, povidon-iodine or sterilized normal saline solution
      (control group). Aerobic and anaerobic bacterial samples were taken from the
      inferior vestibulum mucosa before surgery, 5 min after the start of the operation
      and at the end of the procedure. The results show a statistically significant
      reduction in bacterial counts during procedures in which antiseptics are used to
      wash the oral cavity preoperatively. 1% cetrimide solution was the most
      successful in reducing intra-oral bacterial counts and produced the longest
      lasting antiseptic effect. Chlorhexidine is a good option for procedures longer
      than 1 hour, while povidon-iodine is recommended for procedures lasting up to 1
      hour. Normal saline reduced bacterial counts in the specimen taken 5 min after
      washing but this short-lasting effect is due to mechanical cleansing rather than
      the antiseptic effect.

PMID- 19167189
TI  - A randomised controlled trial comparing fixation of mandibular angle fractures
      with a single miniplate placed either transbuccally and intra-orally, or intra
      orally alone.
AB  - This study compared fixation of simple mandibular angle fractures with a single
      miniplate either placed from a combined transbuccal and intra-oral approach, or
      intra-orally alone. 140 consecutive patients were randomly allocated to the two
      treatment groups. Complications were noted and compared. An email questionnaire
      to all the participating surgeons examined their personal preferences between the
      two methods. 20% of plates needed to be removed during the 3 month study period
      in the combined transbuccal/intra-oral group compared with 36% in the intra-oral
      alone group (p<or=0.05). For the small number of cases (5) that required
      additional fixation, there was no significant difference between the groups. The
      combined transbuccal/intra-oral procedure was safer and more effective than the
      standard intra-oral technique in terms of complications requiring further
      surgery. The surgeons expressed a strong preference (11/12) for fixation using
      the combined transbuccal/oral approach. The principal reasons given were ease of
      use, minimal requirement to bend the plate and facilitation of placement of the
      plate in the neutral mid-point area of the mandible.

PMID- 19167190
TI  - Large cell neuroendocrine carcinoma of the tongue base: case report of an unusual
      location with immunohistochemical analysis.
AB  - A case of large cell neuroendocrine carcinoma (LCNEC) of the tongue base is
      described. It was characterized by solid tumor nests with central necrosis and
      rosette formation resembling basaloid squamous cell carcinoma.
      Immunohistochemical examination revealed that this tumor had neuroendocrine
      differentiation. It was diagnosed as LCNEC of the tongue base. Pulmonary LCNEC is
      a well-established entity, but LCNEC also occurs in other organs. This is the
      first report of mucosal LCNEC in the oral cavity. Basal cells in the normal
      squamous epithelium around the tumor indicated positivity for neural cell
      adhesion molecule and N-cadherin. These cells were considered neuroendocrine
      related cells in the lingual squamous epithelium, which are related to the
      tumorigenesis of mucosal LCNEC in the tongue base.

PMID- 19167191
TI  - Evaluation of reproducibility and reliability of 3D soft tissue analysis using 3D
      stereophotogrammetry.
AB  - In 3D photographs the bony structures are neither available nor palpable,
      therefore, the bone-related landmarks, such as the soft tissue gonion, need to be
      redefined. The purpose of this study was to determine the reproducibility and
      reliability of 49 soft tissue landmarks, including newly defined 3D bone-related
      soft tissue landmarks with the use of 3D stereophotogrammetric images. Two
      observers carried out soft-tissue analysis on 3D photographs twice for 20
      patients. A reference frame and 49 landmarks were identified on each 3D
      photograph. Paired Student's t-test was used to test the reproducibility and
      Pearson's correlation coefficient to determine the reliability of the landmark
      identification. Intra- and interobserver reproducibility of the landmarks were
      high. The study showed a high reliability coefficient for intraobserver (0.97
      (0.90 - 0.99)) and interobserver reliability (0.94 (0.69 - 0.99)). Identification
      of the landmarks in the midline was more precise than identification of the
      paired landmarks. In conclusion, the redefinition of bone-related soft tissue 3D
      landmarks in combination with the 3D photograph reference system resulted in an
      accurate and reliable 3D photograph based soft tissue analysis. This shows that
      hard tissue data are not needed to perform accurate soft tissue analysis.

PMID- 19167192
TI  - DLG3/SAP102 protein expression in malformations of cortical development: a study
      of human epileptic cortex by tissue microarray.
AB  - The human DLG3 gene encodes the synapse-associated protein 102 (SAP102), which is
      concentrated in the postsynaptic densities of excitatory synapses and involved in
      receptor-mediated synaptic transmission via binding to the NR2B subunit of the
      NMDA receptor. In this study, we investigated the expression and cellular
      distribution of the DLG3/SAP102 protein in human epileptic cortex. Tissue
      microarrays of a large number of specimens from patients operated for medically
      intractable epilepsy were used for immunohistochemical screening with anti-DLG3
      antibody. The cellular distribution of the protein was further investigated in
      samples of malformations of cortical development, and the amount of DLG3 protein
      in the total homogenate and in the postsynaptic membrane fraction of these
      samples was quantified by Western blot. We found a strictly neuronal expression
      of DLG3/SAP102 in epileptogenic cortex as well as in non-epileptic human cortex
      used for control. In focal cortical dysplasia and tuberous sclerosis complex, the
      protein was expressed in most neurons including dysplastic neurons, but not in
      giant cells. Increased expression of DLG3 protein was observed in the
      postsynaptic membrane fraction of patients with focal cortical dysplasia. Double
      labeling experiments confirmed the exclusive neuronal character of the DLG3
      expressing cells and the co-localization of the DLG3 protein with the NR2B
      subunit. Our results suggest a putative role for DLG3/SAP102 in cortical
      hyperexcitability and epileptogenicity of malformations of cortical development.

PMID- 19167193
TI  - Lack of association between ABCB1, ABCG2, and ABCC2 genetic polymorphisms and
      multidrug resistance in partial epilepsy.
AB  - ATP-binding cassette (ABC) transporters participate in drug disposition and
      response in various conditions, and many polymorphisms in ABC transporter genes
      have been recognized in association with altered transporter functions of various
      drugs. Studies on epilepsy have focused on the C3435T polymorphism of the ABCB1
      gene, but other ABC transporters are also thought to be involved in the transport
      of antiepileptic drugs. We have evaluated the functional polymorphisms of ABCB1,
      ABCG2, and ABCC2 genes with regard to epilepsy drug response in partial epilepsy,
      and have investigated the potential of combined effects of polymorphisms in more
      than one transporter gene. We studied 6 genetic polymorphisms in 3 transporter
      genes in 193 drug responders and 198 nonresponders. There was no significant
      difference between the two groups, and we did not observe any combined effects of
      ABCB1 and ABCG2 genetic polymorphisms. Our study suggests that genetic
      polymorphisms in ABC transporters may not be significant predictors of drug
      response in epilepsy patients.

PMID- 19167194
TI  - Subclinical hallucinations in adolescent outpatients: an outcome study.
AB  - OBJECTIVE: We assessed the continued prevalence at one year and association with
      clinical variables of subclinical hallucinations ascertained at baseline in a
      cohort of adolescent outpatients referred to a specialized early psychosis
      service. We further assessed the prevalence of psychiatric disorders in
      adolescents presenting subclinical hallucinations. METHOD: 84 adolescent patients
      were sampled from a longitudinal, prospective study that assesses the course of
      clinical and neuropsychological measures in patients identified as at high
      clinical risk for psychosis. Subclinical hallucinations were measured using the
      Scale of Prodromal Symptoms (SOPS) with its companion interview manual
      (Structured Interview for Prodromal Symptoms, SIPS) [Miller, T.J., McGlashan,
      T.H., Woods, S.W., Stein, K., Driesen, N., Corcoran, C.M., Hoffman, R., Davidson,
      L., 1999. Symptom assessment in schizophrenic prodromal states. Psychiatr. Q. 70,
      273-287; McGlashan, T.H., Miller, T.J., Woods, S.W., Rosen, J.L., Hoffman, R.E.,
      Davidson, L., 2001. Structured Interview for Prodromal Syndromes (Version 3.0,
      unpublished manuscript). PRIME Research Clinic, Yale School of Medicine New
      Haven, Connecticut. ], and the Schizophrenia Proneness Instrument -Adult Version
      (SPI-A) [Schultze-Lutter, F., Addington, J., Ruhrmann, S., Klosterkotter, J.,
      2007. Schizophrenia Proneness Instrument (SPI-A). Giovanni Fioriti, Rome, Italy].
      At one-year follow-up, only patients reporting subclinical hallucinations at
      initial assessment were studied. RESULTS: Full remission of subclinical
      hallucinations occurred in over half and at least partial remission in two thirds
      of these patients at one-year follow-up. Mood disorders were present in 62.5% of
      adolescents with subclinical hallucinations at initial assessment. SOPS measures
      for depression, deficient attention and for unusual/delusional thought were
      significantly associated with subclinical hallucinations at baseline. However,
      sustained experience of subclinical hallucinations at one-year follow-up was only
      predicted by the global level of functioning at baseline, while cannabis abuse,
      psychiatric and psychopharmacological treatment were not predictors. CONCLUSIONS:
      Subclinical hallucinations occur across a wide range of mental states in
      adolescents and show high rates of remission. Our results warrant that the
      clinical meaning of such phenomena needs to be carefully weighed against the
      specific developmental phenomena in this particular age range.

PMID- 19167195
TI  - Novel missense mutations in lipase H (LIPH) gene causing autosomal recessive
      hypotrichosis (LAH2).
AB  - BACKGROUND: Autosomal recessive hypotrishosis (LAH2) is a rare form of alopecia
      characterized by sparse hair on scalp, sparse to absent eyebrows and eyelashes,
      and sparse auxiliary and body hair. However, affected male individuals have
      normal beard hair. Mutations in lipase H (LIPH) gene, located on chromosome
      3q26.33, have been shown to be responsible for LAH2 type of hypotrichosis.
      OBJECTIVES: To search for pathogenic mutations in LIPH gene at LAH2 locus in
      Pakistani families demonstrating autosomal recessive hypotrichosis. METHODS: In
      the present study we have ascertained two large unrelated consanguineous
      Pakistani families (A and B) inherited autosomal recessive form of hypotrichosis.
      Linkage in these families was searched by genotyping microsatellite markers
      linked to autosomal recessive hypotrichosis loci LAH1, LAH2 and LAH3. Affected
      individuals showed homozygosity to the microsatellite markers tightly linked to
      LIPH gene at LAH2 locus on chromosome 3q26.33. These families were then subjected
      to direct sequencing of the LIPH gene. RESULTS: Sequence analysis of the LIPH
      gene revealed two novel missense mutations (c.2T>C; p.M1T and c.322T>C; p.W108R)
      in the two families. CONCLUSION: The mutations reported here are the first
      missense mutations identified in the LIPH gene, which extend the body of
      evidences implicating the LIPH gene in the pathogenesis of human hereditary hair
      loss.

PMID- 19167196
TI  - Temporal trends, risk factors and outcomes in albicans and non-albicans
      candidaemia: an international epidemiological study in four multidisciplinary
      intensive care units.
AB  - This multicentre study (i) evaluated geographic and temporal changes in
      candidaemia ecology in the critically ill, (ii) identified risk factors
      associated with non-albicans candidaemia and (iii) examined the association of
      Candida ecology with mortality. A retrospective cohort study of patients who
      developed candidaemia in four general Intensive Care Units located in Australia,
      Greece, Belgium and Brazil was performed. Two hundred Candida organisms were
      identified by positive blood culture in 189 patients, including 112 Candida
      albicans (56.0%), 38 Candidaglabrata (19.0%), 21 Candidaparapsilosis (10.5%), 18
      Candidatropicalis (9.0%), 6 Candidakrusei (3.0%), 1 Candidafamata (0.5%), 1
      Candidazeylanoides (0.5%) and 3 non-differentiated Candida spp. (1.5%). No trend
      towards increased non-albicans species over the study period (P=0.68) or by
      geographic area (P=0.35) was demonstrated. Independent risk factors for non
      albicans candidaemia included: female gender [odds ratio (OR) 2.09, 95%
      confidence interval (CI) 1.13-3.86] and increased central venous catheter days
      (OR 1.16 per 5-day interval, 95% CI 1.05-1.28). Mortality in the non-albicans
      group was non-significantly higher than in the albicans group (65% vs. 53%;
      P=0.10). This study is unique in that a large number of intensive care
      candidaemias in four geographically diverse units have been studied.

PMID- 19167197
TI  - Alprazolam treatment immediately after stress exposure interferes with the normal
      HPA-stress response and increases vulnerability to subsequent stress in an animal
      model of PTSD.
AB  - BACKGROUND: In light of clinical reports suggesting that early benzodiazepine
      administration interferes with long-term recovery from traumatic stress, a
      prospective animal model for PTSD was employed to assess the short- and long-term
      effects of a brief course of alprazolam following stress exposure. METHOD:
      Animals exposed to stress were treated either 1 h or 7 days later with alprazolam
      or vehicle for 3-days. Outcome measures included behavior in the elevated plus
      maze (EPM) and acoustic startle response (ASR) tests 30 days after initial
      exposure and freezing behavior upon exposure to a trauma-cue on day 31. One group
      was repeatedly exposed to the triggering trauma shortly before and after
      treatment and assessed as above. Circulating corticosterone levels were assessed
      4 h after initiation of alprazolam and post-treatment. Pre-set cut-off behavioral
      criteria classified exposed animals according to their EPM and ASR response
      patterns into 'extreme', 'minimal,' or 'partial' behavioral response for analysis
      of prevalence rates. RESULTS: Immediate alprazolam treatment was effective in
      alleviating anxiety at day 4. No observable anxiolytic effects remained at day
      30. Immediate alprazolam also resulted in significantly greater freezing response
      to trauma-cue exposure and in extreme responses to double-exposure.
      Corticosterone levels were significantly suppressed by alprazolam during
      treatment and rebounded after cessation. CONCLUSION: A brief course of alprazolam
      in the immediate aftermath of stress-exposure is associated with less favorable
      responses to additional stress-exposure later on. Alprazolam was associated with
      a significant attenuation of the HPA-response, suggesting a possible link between
      initial HPA-axis response disruption and the subsequent unfavorable outcomes.

PMID- 19167198
TI  - Biosynthesis of cadmium sulfide nanoparticles by photosynthetic bacteria
      Rhodopseudomonas palustris.
AB  - A simple route for the synthesis of cadmium sulfide nanoparticles by
      photosynthetic bacteria Rhodopseudomonas palustris has been demonstrated in this
      work. The cadmium sulfate solution incubated with R. palustris biomass changed to
      a yellow color from 48 h onward, indicating the formation of cadmium sulfide
      nanoparticles. The purified solution yielded the maximum absorbance peak at 425
      nm due to CdS particles in the quantum size regime. Also, X-ray analysis of the
      purified nanoparticles confirmed the formation of cadmium sulfide. Transmission
      electron microscopic analysis of the samples showed a uniform distribution of
      nanoparticles, having an average size of 8.01+/-0.25 nm, and its corresponding
      electron diffraction pattern confirmed the face-centered cubic (fcc) crystalline
      structure of cadmium sulfide. Furthermore, it was observed that the cysteine
      desulfhydrase producing S(2-) in the R. palustris was located in cytoplasm, and
      the content of cysteine desulfhydrase depending on the growth phase of cells was
      responsible for the formation of CdS nanocrystal, while protein secreted by the
      R. palustris stabilized the cadmium sulfide nanoparticles. In addition, R.
      palustris was able to efficiently transport CdS nanoparticles out of the cell.

PMID- 19167199
TI  - Interaction of bovine serum albumin (BSA) with ionic surfactants evaluated by
      electron paramagnetic resonance (EPR) spectroscopy.
AB  - EPR spectra of 5- and 16-doxyl stearic acid nitroxide probes (5-DSA and 16-DSA,
      respectively) bound to bovine serum albumin (BSA) revealed that in the presence
      of ionic surfactants, at least, two label populations coexist in equilibrium. The
      rotational correlation times (tau) indicated that component 1 displays a more
      restricted mobility state, associated to the spin labels bound to the protein;
      the less immobilized component 2 is due to label localization in the surfactant
      aggregates. For both probes, the increase of surfactant concentration leads to
      higher motional levels of component 1 followed by a simultaneous decrease of this
      fraction of nitroxides and its conversion into component 2. For 10mM
      cethyltrimethylammonium chloride (CTAC), the nitroxides are 100% bound to the
      protein, whereas at 10mM N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate
      (HPS) and sodium dodecyl sulfate (SDS) the fractions of bound nitroxides are
      reduced to 18% and 86%, respectively. No significant polarity changes were
      observed in the whole surfactant concentration range for component 1. Moreover,
      at higher surfactant concentration, component 2 exhibited a similar polarity as
      in the pure surfactant micelles. For 16-DSA the surfactant effect is different:
      at 10mM of HPS and CTAC the fractions of bound nitroxides are 76% and 49%,
      respectively, while at 10mM SDS they are present exclusively in a micellar
      environment, consistent with 100% of component 2. Overall, both SDS and HPS are
      able to effectively displace the nitroxide probes from the protein binding sites,
      while CTAC seems to affect the nitroxide binding to a significantly smaller
      extent.

PMID- 19167200
TI  - Oncological emergency admissions to the Norfolk and Norwich University Hospital:
      an audit of current arrangements and patient satisfaction.
AB  - AIMS: To assess current emergency admission pathways for patients with cancer,
      reasons for admission, subsequent management and patient perceptions of and
      satisfaction with the care they received. MATERIALS AND METHODS: A prospective
      audit was carried out of emergency admissions of patients with cancer over a 3
      month period from the beginning of October to the end of December 2007,
      collecting data at two time points a week, giving a total of 60 patients. The
      date, time and place of admission, patient demographics (age, gender) and reasons
      for admission, diagnosis and care pathway were analysed. Questionnaires were
      completed by a subgroup of 12 patients to assess satisfaction with care. RESULTS:
      The mean age was 63.62 years with a range of 29-85 years. Thirty patients were 65
      years or older. Lung, bowel, breast, prostate and oesophageal cancers were the
      most prevalent in terms of emergency admissions. Admissions were grouped into
      admission due to cancer progression (30/60), treatment-related reasons (20) or
      for other medical conditions (10). Specialist investigation or management was
      required by all. Twenty-nine patients were admitted to the Emergency Assessment
      Unit, 27 were admitted directly to the oncology ward and four patients were
      admitted through the Accident and Emergency Department. Three patients might have
      been more appropriately admitted to palliative care services. There was
      correlation with patient satisfaction and admission to the oncology ward rather
      than through the Emergency Assessment Unit first. CONCLUSION: The cancer burden
      is increasing, with more patients with cancer being admitted as emergencies.
      Patients seem to favour continuity of care and admission to an oncology ward
      directly. Further research needs to be carried out in this area as to how best
      care may be achieved, taking into account local resources and the changes in
      practice that have come from continuing treatment much longer into the course of
      the disease. The organisation of healthcare services has to take account of
      patient preference to balance efficiency and patient satisfaction. Training in
      palliative oncology may need to be extended to other groups than oncologists.

PMID- 19167201
TI  - Early and locally advanced breast cancer: diagnosis and treatment National
      Institute for Health and Clinical Excellence guideline 2009.

PMID- 19167203
TI  - Composition analysis of dental solid waste in Brazil.
AB  - When developing proper waste management strategies, it is essential to
      characterize the volume and composition of solid waste. The aim of this work was
      to evaluate the composition of dental waste produced by three dental health
      services in Belo Horizonte, Minas Gerais State, Brazil. Two universities, one
      public and one private, and one public dental health service were selected. Waste
      collection took place from March to November 2007. During this period, three
      samples were collected from each dental health service. The total amount of
      dental waste produced in one day of dental work was manually separated into three
      categories: infectious and potentially infectious waste, accounting for 24.3% of
      the total waste; non-infectious waste, accounting for 48.1%; and domestic-type
      waste, accounting for 27.6% (percentages are for mean weights of solid waste).
      Our results showed that most of the waste considered as biomedical may be
      misclassified, consequently making the infectious waste amount appear much
      larger. In addition, our results suggest that the best waste minimization method
      is recycling, and they help to define an appropriate waste management system in
      all three of the dental health services involved in this study.

PMID- 19167204
TI  - Use of steel fibres recovered from waste tyres as reinforcement in concrete: pull
      out behaviour, compressive and flexural strength.
AB  - The increasing amount of waste tyres worldwide makes the disposition of tyres a
      relevant problem to be solved. In the last years over three million tons of waste
      tyres were generated in the EU states [ETRA, 2006. Tyre Technology International 
      Trends in Tyre Recycling. http://www.etra-eu.org]; most of them were disposed
      into landfills. Since the European Union Landfill Directive (EU Landfill, 1999)
      aims to significantly reduce the landfill disposal of waste tyres, the
      development of new markets for the tyres becomes fundamental. Recently some
      research has been devoted to the use of granulated rubber and steel fibres
      recovered from waste tyres in concrete. In particular, the concrete obtained by
      adding recycled steel fibres evidenced a satisfactory improvement of the fragile
      matrix, mostly in terms of toughness and post-cracking behaviour. As a
      consequence RSFRC (recycled steel fibres reinforced concrete) appears a promising
      candidate for both structural and non-structural applications. Within this
      context a research project was undertaken at the University of Salento (Italy)
      aiming to investigate the mechanical behaviour of concrete reinforced with RSF
      (recycled steel fibres) recovered from waste tyres by a mechanical process. In
      the present paper results obtained by the experimental work performed up to now
      are reported. In order to evaluate the concrete-fibres bond characteristics and
      to determine the critical fibre length, pull-out tests were initially carried
      out. Furthermore compressive strength of concrete was evaluated for different
      volume ratios of added RSF and flexural tests were performed to analyze the post
      cracking behaviour of RSFRC. For comparison purposes, samples reinforced with
      industrial steel fibres (ISF) were also considered. Satisfactory results were
      obtained regarding the bond between recycled steel fibres and concrete; on the
      other hand compressive strength of concrete seems unaffected by the presence of
      fibres despite their irregular geometric properties. Finally, flexural tests
      furnished in some cases results comparable to those obtained when using ISF as
      concerns the post-cracking behaviour.

PMID- 19167202
TI  - Assembly of ribosomes and spliceosomes: complex ribonucleoprotein machines.
AB  - Ribosomes and spliceosomes are ribonucleoprotein nanomachines that catalyze
      translation of mRNA to synthesize proteins and splicing of introns from pre
      mRNAs, respectively. Assembly of ribosomes involves more than 300 proteins and
      RNAs, and that of spliceosomes over 100 proteins and RNAs. Construction of these
      enormous ribonucleoprotein particles (RNPs) is a dynamic process, in which the
      nascent RNPs undergo numerous ordered rearrangements of RNA-RNA, RNA-protein, and
      protein-protein interactions. Here we outline similar principles that have
      emerged from studies of ribosome and spliceosome assembly. Constituents of both
      RNPs form subassembly complexes, which can simplify the task of assembly and
      segregate functions of assembly factors. Reorganization of RNP topology, and
      proofreading of proper assembly, are catalyzed by protein- or RNA-dependent
      ATPases or GTPases. Dynamics of intermolecular interactions may be facilitated or
      regulated by cycles of post-translational modifications. Despite this repertoire
      of tools, mistakes occur in RNP assembly or in processing of RNA substrates.
      Quality control mechanisms recognize and turnover misassembled RNPs and reject
      improper substrates.

PMID- 19167205
TI  - Electropolymerization of preoxidized catecholamines on Prussian blue matrix to
      immobilize glucose oxidase for sensitive amperometric biosensing.
AB  - We examine here the electropolymerization of electrochemically or chemically
      preoxidized catecholamines in glucose oxidase (GOx)-containing neutral solutions
      to efficiently immobilize the enzyme at Prussian blue-modified Au electrodes for
      sensitive amperometric biosensing of glucose. The electrochemical quartz crystal
      microbalance (EQCM) was used to track various electrode-modification processes.
      The optimized poly(dopamine)-based glucose biosensor displayed a sensitivity of
      35 microA mM(-1) cm(-2) and a limit of detection of 0.3 microM at 0.7 V vs. SCE,
      and similar results were obtained at -0.05 V vs. SCE, which are obviously better
      than those from preoxidation-free conventional electropolymerization. The
      immobilized GOx retained high enzymatic specific activity, as quantified by UV
      vis spectrophotometry and EQCM. L-noradrenaline could similarly electropolymerize
      and the resultant enzyme film gave equivalent biosensing characteristics, but the
      electropolymerization of EP was less efficient and the resultant enzyme film
      showed notably poorer performance.

PMID- 19167206
TI  - SU-8 microprobe with microelectrodes for monitoring electrical impedance in
      living tissues.
AB  - This paper presents a minimally invasive needle-shaped probe capable of
      monitoring the electrical impedance of living tissues. This microprobe consists
      of a 160 microm thick SU-8 substrate containing four planar platinum (Pt)
      microelectrodes. We design the probe to minimize damage to the surrounding tissue
      and to be stiff enough to be inserted in living tissues. The proposed batch
      fabrication process is low cost and low time consuming. The microelectrodes
      obtained with this process are strongly adhered to the SU-8 substrate and their
      impedance does not depend on frequency variation. In vitro experiments are
      compared with previously developed Si and SiC based microprobes and results
      suggest that it is preferable to use the SU-8 based microprobes due to their
      flexibility and low cost. The microprobe is assembled on a flexible printed
      circuit FPC with a conductive glue, packaged with epoxy and wired to the external
      instrumentation. This flexible probe is inserted into a rat kidney without
      fracturing and succeeds in demonstrating the ischemia monitoring.

PMID- 19167207
TI  - Development of an electrochemical immunosensor for aflatoxin M1 in milk with
      focus on matrix interference.
AB  - A simple sensor method was developed for aflatoxin M(1) analysis to be applied
      directly with milk by using antibody modified screen-printed carbon working
      electrode with carbon counter and silver-silver chloride pseudo-reference
      electrode. A competitive ELISA assay format was constructed on the surface of the
      working electrode using 3,3,5',5'-tetramethylbenzidine dihyrochloride
      (TMB)/H(2)O(2) electrochemical detection scheme with horseradish peroxidase (HRP)
      as the enzyme label. The performance of the assay and the sensor was optimised
      and characterised in pure buffer conditions before applying to milk samples.
      Extensive interference to the electroanalytical signal was observed upon the
      analysis of milk. Through a series of chemical fractionations of the milk, and
      testing the electrochemical properties of the fractions, the interference was
      attributed to whey proteins with focus towards alpha-lactalbumin. A simple pre
      treatment technique of incorporating 18 mM calcium chloride, in the form of
      Dulbucco's PBS, in a 1:1 ratio to the milk sample or standards and also to the
      washing buffer stabilised the whey proteins in solution and eliminate the
      interfering signal. The resulting immunosensor was interference free and achieved
      a limit of detection of 39 ng l(-1) with a linear dynamic detection range up to
      1000 ng l(-1). The developed immunosensor method was compared to a commercial
      ELISA kit and an in-house HPLC method. The immunsensor was comparable, in term of
      sensitivity, but vastly superior in term of portability and cost therefore a key
      instrument for the detection of aflatoxin M(1) at the source of the
      contamination.

PMID- 19167208
TI  - An ionic liquid supported CeO2 nanoshuttles-carbon nanotubes composite as a
      platform for impedance DNA hybridization sensing.
AB  - A novel nanocomposite membrane, comprising of nanosized shuttle-shaped cerium
      oxide (CeO(2)), single-walled carbon nanotubes (SWNTs) and hydrophobic room
      temperature ionic liquid (RTIL) 1-butyl-3-methylimidazolium hexafluorophosphate
      (BMIMPF(6)), was developed on the glassy carbon electrode (GCE) for
      electrochemical sensing of the immobilization and hybridization of DNA. The
      properties of the CeO(2)-SWNTs-BMIMPF(6)/GCE, the characteristics of the
      immobilization and hybridization of DNA were studied by cyclic voltammetry and
      electrochemical impedance spectroscopy (EIS) using [Fe(CN)(6)](3-/4-) as the
      redox indicator. The synergistic effect of nano-CeO(2), SWNTs and RTIL could
      dramatically enhance the sensitivity of DNA hybridization recognition. The
      electron transfer resistance (R(et)) of the electrode surface increased after the
      immobilization of probe ssDNA on the CeO(2)-SWNTs-BMIMPF(6) membrane and rose
      further after the hybridization of the probe ssDNA with its complementary
      sequence. The remarkable difference between the R(et) value at the probe DNA
      immobilized electrode and that at the hybridized electrode could be used for
      label-free EIS detection of the target DNA. The sequence-specific DNA of
      phosphoenolpyruvate carboxylase (PEPCase) gene from transgenically modified rape
      was detected by this DNA electrochemical biosensor. Under optimal conditions, the
      dynamic range for detecting the sequence-specific DNA of the PEPCase gene was
      from 1.0x10(-12) mol/L to 1.0x10(-7) mol/L, and the detection limit was 2.3x10(
      13) mol/L, suggesting that the CeO(2)-SWNTs-BMIMPF(6) nanocomposite hold great
      promises for the applications in sensitive electrochemical biosensor.

PMID- 19167209
TI  - An electrochemical immunoassay for protein based on bio bar code method.
AB  - An electrochemical bio bar code assay based on DNA modified gold nanoparticles
      (Au NPs) provides a nonenzymatic method for quantitative detection of protein. By
      sandwiching an antigen (Ag) between a magnetic bead (MB) modified with antibody
      (Ab) and an amplifier Au NP bifunctioned with second Ab and bio bar code DNA, the
      detection method was established. Subsequent electrochemical stripping analysis
      of the cadmium dissolved from CdS NPs on the congregates provided a means to
      quantify the concentration of Ag in the analyte. Using AFP detection as a model,
      we demonstrate a linear dose response in the range from 0.02 to 3.5 ng/mL. The
      detection limit of this assay for AFP determined is 9.6 pg/mL, 100-fold
      improvement compared to the best enzyme-linked immunosorbent assay (ELISA)
      system. In addition, the amount of anti-AFP loaded on one MB, and the numbers of
      the secondary anti-AFP and bio bar code DNA modified on one Au NP were all
      determined for the first time. The ratio of MB and anti-AFP was approximately
      1/16,700, and the ratios of Au NPs, anti-AFP, bar code DNA probes, and CdS NPs
      were about 1/16/101/77. It would be valuable for clinical immunoassay due to the
      high sensitivity and selectivity.

PMID- 19167210
TI  - Cancer stem cells: a model in the making.
AB  - Cancer stem cells and their potential roles in tumor heterogeneity are currently
      subjects of intense investigation. Studies suggest that these cells may develop
      from any normal cell and have begun to elucidate their molecular profiles. The
      percentage of a tumor composed of cancer stem cells varies greatly, and
      researchers believe that multiple types of these cells may exist in a single
      neoplasm. Cancer stem cells may be formed by epithelial-mesenchymal transition
      and seem to be less prevalent in metastases than in corresponding primary tumors.
      These cells appear to have therapeutic sensitivities different from those of
      cancer cells with more differentiated features. Looking into the many questions
      that remain about the cancer stem cells model might lead to more effective cancer
      prevention, diagnosis, and treatment.

PMID- 19167211
TI  - Hypoxia inducible factor-2alpha: a critical mediator of aggressive tumor
      phenotypes.
AB  - Intra-tumoral hypoxia (low oxygen [O(2)] level) is an independent indicator of
      unfavorable patient diagnosis, and increasing evidence demonstrates that hypoxia
      contributes to a more aggressive tumor phenotype. Adaptation to hypoxia is
      predominantly regulated by two structurally related hypoxia inducible factors,
      HIF-1alpha and HIF-2alpha, which activate the expression of genes involved in
      proliferation, metabolism, angiogenesis, and metastasis. While highly homologous,
      HIF-1alpha and HIF-2alpha have been shown to have different roles in
      tumorigenesis dependent on specific tumor microenvironments. Here we summarize
      recent studies on HIF-2alpha and discuss the potential mechanisms whereby it
      contributes to tumor aggressiveness.

PMID- 19167212
TI  - Towards more patient centred healthcare: A new Consumer Quality Index instrument
      to assess patients' experiences with breast care.
AB  - OBJECTIVE: To develop a Consumer Quality Index (CQ-index) Breast Care instrument
      that measures quality of care from the perspective of patients with (suspicion
      of) breast cancer. METHODS: To develop a pilot questionnaire, three focus group
      discussions with breast cancer patients were performed. The questionnaire was
      sent to 1197 patients. We performed psychometric and descriptive analyses to
      optimise the new instrument. RESULTS: Focus group discussions revealed nine main
      themes related to breast care quality. Psychometric analyses resulted in 15
      reliable scales. The final instrument consisted of 152 items, of which 118 items
      regarded patients' experiences. The aspect with the highest need for quality
      improvement was informing patients about a second opinion. CONCLUSION: The CQ
      index Breast Care (CQI-BC) instrument provides a good starting point for further
      research on the quality of breast care seen from the perspective of patients. The
      newly developed instrument can be used by different stakeholders for future
      quality monitoring.

PMID- 19167213
TI  - Different antiproliferative effects of matuzumab and cetuximab in A431 cells are
      associated with persistent activity of the MAPK pathway.
AB  - Preclinical studies have shown the potential antitumour efficacy of monoclonal
      antibodies (MAbs) directed to the epidermal growth factor receptor (EGFR). In
      this report, we investigated the cytotoxic effects of the MAb matuzumab (EMD
      72000) towards A431 cells and compared it to cetuximab. While cetuximab induced
      cell cycle arrest and inhibited A431 cell proliferation, matuzumab did not. Both
      MAbs inhibited growth factor induced EGFR, HER2 and AKT phosphorylation; however,
      only cetuximab inhibited ERK 1/2 phosphorylation. Taken together, the data
      indicate that each antibody may elicit different responses on EGFR downstream
      signalling pathways with a distinct impact on A431 cell line survival. When
      combined, MAbs synergistically inhibited cell proliferation and induced EGFR down
      regulation with a strong inhibition of ERK1/2 and AKT phosphorylation. In
      addition, both MAbs efficiently inhibited VEGF expression and induced ADCC,
      highlighting their therapeutic potential in vivo when used either as a single
      agent or in combination.

PMID- 19167214
TI  - Improving the efficacy of cancer immunotherapy.
AB  - A series of cancer vaccines have been evaluated in clinical trials with
      encouraging results, but the demonstration of clinical benefit in confirmatory
      studies has so far proven to be difficult. The development of cancer vaccines is
      hampered by a range of issues particular to this field of research. On 12th March
      2008, the Biotherapy Development Association convened a workshop to discuss
      issues faced by scientists and clinicians involved in the development of cancer
      vaccines. This paper is a review of the field, based on discussions held at the
      BDA workshop, and describes biological barriers encountered in generating
      effective immune responses to tumours, methodological obstacles encountered in
      the improvement of immunological monitoring which aims to improve inter
      laboratory and inter-trial comparisons, challenges in clinical trial design and
      problems posed by the lack of specific regulation for cancer vaccines and the
      impact on their development. Ultimately, a number of general solutions are posed:
      (1) better patient selection, (2) use of multi-modal treatments that affect
      several aspects of the immune system at once, (3) a requirement for the
      development of good biomarkers to stratify patients for selection prior to trial
      and as surrogates for clinical response and (4) harmonisation of SOPs for
      immunological monitoring of clinical trials.

PMID- 19167215
TI  - Thermogravimetric kinetics of crude glycerol.
AB  - The pyrolysis of the crude glycerol from a biodiesel production plant was
      investigated by thermogravimetry coupled with Fourier transform infrared
      spectroscopy. The main gaseous products are discussed, and the thermogravimetric
      kinetics derived. There were four distinct phases in the pyrolysis process of the
      crude glycerol. The presence of water and methanol in the crude glycerol and
      responsible for the first decomposition phase, were shown to catalyse glycerol
      decomposition (second phase). Unlike the pure compound, crude glycerol
      decomposition below 500 K leaves behind a large mass fraction of pyrolysis
      residues (ca. 15%), which eventually partially eliminate in two phases upon
      reaching significantly higher temperatures (700 and 970 K, respectively). An
      improved iterative Coats-Redfern method was used to evaluate non-isothermal
      kinetic parameters in each phase. The latter were then utilised to model the
      decomposition behaviour in non-isothermal conditions. The power law model (first
      order) predicted accurately the main (second) and third phases in the pyrolysis
      of the crude glycerol. Differences of 10-30 kJ/mol in activation energies between
      crude and pure glycerol in their main decomposition phase corroborated the
      catalytic effect of water and methanol in the crude pyrolysis. The 3-D diffusion
      model more accurately reproduced the fourth (last) phase, whereas the short
      initial decomposition phase was poorly simulated despite correlation coefficients
      ca. 0.95-0.96. The kinetics of the 3rd and 4th decomposition phases, attributed
      to fatty acid methyl esters cracking and pyrolysis tarry residues, were sensitive
      to the heating rate.

PMID- 19167216
TI  - Design and synthesis of a beta-lactamase activated 5-fluorouracil prodrug.
AB  - An efficient synthesis of a 5-fluorouracil-cephalosporin prodrug is described for
      use against colorectal and other cancers in antibody and gene-directed therapies.
      The compound shows stability in aqueous media until specifically activated by
      beta-lactamase (betaL). The kinetic parameters of the 5-fluorouracil
      cephalosporin conjugate were determined in the presence of Enterobacter cloacae
      P99 betaL (ECl betaL) revealing a K(m)=95.4 microM and V(max)=3.21 microMol min(
      1) mg(-1). The data compare favorably to related systems that have been reported
      and enable testing of this prodrug against cancer cell lines in vitro and in
      vivo.

PMID- 19167217
TI  - Nonactin biosynthesis: setting limits on what can be achieved with precursor
      directed biosynthesis.
AB  - Nonactin, produced by Streptomyces griseus ETH A7796, is a macrotetrolide
      assembled from nonactic acid. It is an effective inhibitor of drug efflux in
      multidrug resistant erythroleukemia K562 cells at sub-toxic concentrations and
      has been shown to possess both antibacterial and antitumor activity. As total
      synthesis is impractical for the generation of nonactin analogs we have studied
      precursor-directed biosynthesis as an alternative as it is known that nonactic
      acid can serve as a nonactin precursor in vivo. To determine the scope of the
      approach we prepared and evaluated a furan-based nonactic acid derivative, 11.
      Although no new nonactin analogs were detected when 11 was administered to S.
      griseus fermentative cultures, a significant inhibition of nonactin biosynthesis
      was noted (IC(50) approximately 100 microM). Cell mass, nonactic acid production
      and the generation of other secondary metabolites in the culture were unaffected
      by 11 demonstrating that 11 selectively inhibited the assembly of nonactin from
      nonactic acid. While we were unable to generate new nonactin analogs we have
      discovered, however, a useful inhibitor that we can use to probe the mechanism of
      nonactin assembly with the ultimate goal of developing more successful precursor
      directed biosynthesis transformations.

PMID- 19167218
TI  - Synthesis and structure-function analysis of Fe(II)-form-selective antibacterial
      inhibitors of Escherichia coli methionine aminopeptidase.
AB  - Methionine aminopeptidase (MetAP) is a promising target for the development of
      novel antibacterial, antifungal and anticancer therapy. Based on our previous
      results, catechol derivatives coupled with a thiazole or thiophene moiety showed
      high potency and selectivity toward the Fe(II)-form of Escherichia coli MetAP,
      and some of them clearly showed antibacterial activity, indicating that Fe(II) is
      likely the physiologically relevant metal for MetAP in E. coli and other
      bacterial cells. To further understand the structure-function relationship of
      these Fe(II)-form selective MetAP inhibitors, a series of catechol derivatives
      was designed and synthesized by replacement of the thiazole or thiophene moiety
      with different five-membered and six-membered heterocycles. Inhibitory activities
      of these newly synthesized MetAP inhibitors indicate that many five- and six
      membered rings can be accommodated by MetAP and potency on the Fe(II)-form can be
      improved by introducing substitutions on the heterocyles to explore additional
      interactions with the enzyme. The furan-containing catechols 11-13 showed the
      highest potency at 1muM on the Fe(II)-form MetAP, and they were also among the
      best inhibitors for growth inhibition against E. coli AS19 strain. These findings
      provide useful information for the design and discovery of more effective MetAP
      inhibitors for therapeutic applications.

PMID- 19167219
TI  - Synthesis and promotion angiogenesis effect of chrysin derivatives coupled to NO
      donors.
AB  - Two types of new chrysin derivatives were prepared by coupling NO donors of alkyl
      nitrate and furazan derivatives and were fully characterized by (1)H NMR and
      other techniques. These compounds were tested in human umbilical vein endothelial
      cells (HUVECs-12) and all the compounds exhibited cell proliferation. Notable
      effects of promoting angiogenesis were observed for all the modified compounds
      using chick chorioallantoic membrane (CAM) assay.

PMID- 19167220
TI  - Synthesis and antimicrobial activity of some new pyrazole derivatives containing
      a ferrocene unit.
AB  - A series of new imines and amines have been synthesized by condensation of 1H-3
      ferrocenyl-1-phenylpyrazole-4-carboxaldehyde with the corresponding amines,
      followed by reduction with sodium borohydride. The synthesized compounds have
      been screened for their in vitro antimicrobial activity against 11 bacteria and
      three fungal/yeast strains, using disc diffusion and broth microdilution
      susceptibility assays. They have shown a wide range of activities, from
      completely inactive to the highly active compounds.

PMID- 19167221
TI  - Stieglitz rearrangement of N,N-dichloro-beta,beta-disubstituted taurines under
      mild aqueous conditions.
AB  - New topical anti-infectives comprised of N,N-dichloro-beta,beta-disubstituted
      taurines [Tetrahedron Lett.2008, 49, 2193; Biorg. Med. Chem. Lett. 2009, 19, 196]
      have been examined for structure-stability relationships (SSR) based upon various
      alkyl, heteroalkyl and cycloalkyl beta-substitutions. These substitutions affect
      order-of-magnitude changes in the aqueous stability of these N,N-dichloroamines
      which can undergo Stieglitz rearrangement of alkyl groups under extremely mild
      conditions (H(2)O, pH 4-7, 0-20 mM acetate or phosphate buffer, 20-40 degrees C).
      This process produces beta-ketosulfonic acids which function as substrates for
      chlorination by the N-chlorotaurines which leads to their further degradation.

PMID- 19167222
TI  - Bis(hetero)aryl derivatives as unique kinesin spindle protein inhibitors.
AB  - Synthesis of 4-(4-tert-butylphenyl)pyridine analogues as kinesin spindle protein
      (KSP) inhibitors, SAR, cytotoxicity and mitotic arrest in HeLa cells are
      described. Interestingly, PVZB1194 showed potent KSP inhibition only in the
      presence of microtubules and distinct KSP localization from a known KSP inhibitor
      S-trytylcysteine analogue in mitosis. The observations would have resulted from a
      different molecular mechanism of KSP inhibition and suggest a novel biological
      regulation for KSP in mitosis.

PMID- 19167223
TI  - Peripheral neuropathy and 46XY gonadal dysgenesis: a heterogeneous entity.
AB  - Gonadal dysgenesis with normal male karyotype (46XY) is a sexual differentiation
      disorder. So far three patients have been reported presenting the association of
      46XY gonadal dysgenesis with peripheral neuropathy. Examination of sural nerves
      revealed minifascicle formation in two of them. In one patient, a mutation was
      found in desert hedgehog homolog (Drosophila), a gene important in gonadal
      differentiation and peripheral nerve development. We studied neuropathological
      and molecular genetic aspects of a patient with 46XY gonadal dysgenesis and
      peripheral neuropathy. Examination of a sural nerve biopsy specimen revealed an
      axonal neuropathy with pronounced axonal loss, limited signs of axonal
      regeneration and no minifascicle formation. A normal male karyotype was found
      (46XY) without micro-deletions in the Y chromosome. No mutations were found in
      the sex determining region Y gene, peripheral myelin protein 22, Myelin Protein
      Zero, Gap-Junction protein Beta 1, Mitofusin 2 or desert hedgehog homolog. The
      absence of minifascicle formation and the absence of a mutation in desert
      hedgehog homolog in this patient with gonadal dysgenesis and peripheral
      neuropathy expand the clinical and genetic heterogeneity of this rare entity.

PMID- 19167224
TI  - Dysphagia is present but mild in myotonic dystrophy type 2.
AB  - The phenotype of myotonic dystrophy type 2 (DM2) shows similarities as well as
      differences to that of myotonic dystrophy type 1 (DM1). Dysphagia, a predominant
      feature in DM1, has not yet been examined in DM2. In a recent nationwide
      questionnaire survey of gastrointestinal symptoms in DM2, 12 out of 29 DM2
      patients reported to have difficulty in swallowing for solid food. The aim of the
      study was to investigate the presence of dysphagia in patients with genetically
      proven DM2 who reported difficulty in swallowing for solid food at the
      questionnaire survey. Swallowing function and fiberoptic endoscopic evaluation of
      swallowing (FEES) were examined by a speech therapist and otorhinolaryngologist,
      respectively. In DM2 patients who reported difficulty in swallowing the presence
      of dysphagia could be confirmed (clinically in 100%, by FEES in 88%). A
      correlation exists between Dysphagia Outcome and Severity Score (DOSS) and age
      (p=0.05). None of the patients was underweight, and none of the patients had
      suffered aspiration pneumonia in the past. Dysphagia is present among DM2
      patients and is more severe in older patients. However, dysphagia is generally
      mild, and do not lead to weight loss, or aspiration pneumonia.

PMID- 19167225
TI  - Discovery of lignin in seaweed reveals convergent evolution of cell-wall
      architecture.
AB  - Lignified cell walls are widely considered to be key innovations in the evolution
      of terrestrial plants from aquatic ancestors some 475 million years ago. Lignins,
      complex aromatic heteropolymers, stiffen and fortify secondary cell walls within
      xylem tissues, creating a dense matrix that binds cellulose microfibrils and
      crosslinks other wall components, thereby preventing the collapse of conductive
      vessels, lending biomechanical support to stems, and allowing plants to adopt an
      erect-growth habit in air. Although "lignin-like" compounds have been identified
      in primitive green algae, the presence of true lignins in nonvascular organisms,
      such as aquatic algae, has not been confirmed. Here, we report the discovery of
      secondary walls and lignin within cells of the intertidal red alga Calliarthron
      cheilosporioides. Until now, such developmentally specialized cell walls have
      been described only in vascular plants. The finding of secondary walls and lignin
      in red algae raises many questions about the convergent or deeply conserved
      evolutionary history of these traits, given that red algae and vascular plants
      probably diverged more than 1 billion years ago.

PMID- 19167226
TI  - Mature Drosophila meiosis I spindles comprise microtubules of mixed polarity.
AB  - New information has been obtained recently regarding microtubule organization in
      Xenopus extract spindles. These spindles assemble in vitro by chromatin-mediated
      microtubule nucleation and consist of randomly interspersed long and short
      microtubules with minus ends distributed throughout the spindle. Fluorescence
      speckle microscopy has led to the proposal that the Xenopus steady-state spindles
      contain two overlapping arrays of parallel or antiparallel microtubules with
      differing poleward-flux velocities. Although some of these features have also
      been reported for C. elegans female meiotic spindles, it is not clear whether
      they are representative of microtubule organization and dynamics in oocyte
      meiotic spindles. Here we examine anastral meiosis I spindles of live Drosophila
      oocytes expressing the microtubule plus end-tracking protein, EB1, fused to GFP,
      and find fluorescent particles throughout the spindle and movement toward both
      the poles and the equator. EB1 particle velocities, corresponding to microtubule
      growth rates, are similar in both directions, but slower than growth from the
      poles in mitotic spindles of early embryos. Meiosis I spindles yielded data from
      photobleaching analysis showing similar microtubule growth rates and dynamics at
      the poles and the equator, consistent with spindle microtubules of mixed
      polarity, differing from early-embryo mitotic spindles.

PMID- 19167227
TI  - Septin-mediated uniform bracing of phospholipid membranes.
AB  - Cell shape is determined by the interplay between the lipid bilayer and the
      underlying network of protein polymers. We explored unknown determinants involved
      in cell morphogenesis as factors that transform phospholipid-based liposomes
      (diameter 5-20 microm). Unlabeled giant liposomes, observed through dark-field
      optics, were metastable in an aqueous suspension. In contrast, liposomes robustly
      protruded uniform tubules immediately after the addition of a brain extract to
      the suspension. The tubulation reaction was greatly facilitated when the
      liposomes contained PIP or PIP2. Biochemical analysis of the brain extract
      revealed that heteromeric complexes of septins, a family of polymerizing GTP/GDP
      binding proteins, are responsible for the membrane transformation.
      Ultrastructural analysis established that each membrane tubule (diameter 0.43 +/-
      0.079 microm) is braced by a circumferential array of septin filaments. Although
      submembranous septin assemblies are associated with diverse cortical
      morphogenesis from yeast to mammals, the biophysical basis for the septin
      membrane interplay remains largely unknown. Further, there is a biochemical
      discrepancy between the fast septin remodeling in cells and their slow self
      assembly in vitro. This membrane-facilitated fast septin assembly demonstrated
      for the first time by our unique experimental system should provide important
      clues to characterize these processes.

PMID- 19167228
TI  - Chlamydomonas CAV2 encodes a voltage- dependent calcium channel required for the
      flagellar waveform conversion.
AB  - Cilia and flagella can alter their beating patterns through changes in membrane
      excitation mediated by Ca(2+) influx. The ion channel that generates this Ca(2+)
      influx and its cellular distribution have not been identified. In this study, we
      analyzed the Chlamydomonas ppr2 mutant, which is deficient in the production of a
      flagellar Ca(2+) current and consequently has a defective photophobic response
      and mechanoshock response. ppr2 had a mutation in CAV2, which encodes a homolog
      of the alpha(1) subunit of voltage-dependent calcium channels (VDCCs). CAV2 has
      four domains, each with six transmembrane segments and EEEE loci in the ion
      selective filter, which are typical of VDCCs in vertebrates. Interestingly, we
      found that CAV2 primarily localized toward the distal part of flagella. We
      provide evidence that CAV2 is transported toward the flagellar tip via
      intraflagellar transport (IFT) because CAV2 accumulated near the flagellar base
      when IFT was blocked. The results of this study suggest that the Ca(2+) influx of
      Chlamydomonas flagella is mediated by the VDCC, CAV2, whose distribution is
      biased to the distal region of the flagellum.

PMID- 19167229
TI  - Cortical and subcortical connections within the pedunculopontine nucleus of the
      primate Macaca mulatta determined using probabilistic diffusion tractography.
AB  - The anatomical connections of the pedunculopontine nucleus (PPN), a brainstem
      structure associated with locomotion, have been determined recently in healthy
      humans using probabilistic diffusion tractography (PDT). In order to compare
      these with histologically demonstrated connections of the PPN in monkeys, and
      thus to support the use of PDT in humans, we have carried out PDT in a fixed
      rhesus monkey (Macaca mulatta) brain. Probabilistic diffusion tractography was
      carried out in a fixed post-mortem rhesus monkey brain using diffusion data
      acquired at 3T MRI (60 directions x 5 averages, b=3000 s/mm(2), matrix size=104 x
      132 x 96, 720 x 720 x 720 microm voxels). We identified the major connections of
      the PPN from single seed voxels that could be confidently located within the
      nucleus on the diffusion images. The organisation of these connections within a 3
      x 3 x 3 voxel ( approximately 10 mm(3)) region surrounding the initial seed voxel
      was then examined. PDT confirmed that the rhesus monkey PPN connections with the
      basal ganglia and motor cortical areas matched those previously demonstrated
      using conventional anatomical tracing techniques. Furthermore, although the
      organisation of subcortical connections within the PPN has not been extensively
      demonstrated in animals, we show here in a rhesus monkey that there are clearly
      separated connections of the PPN with the thalamus, substantia nigra, and
      subthalamic nucleus. Thus, in addition to increasing confidence in the accuracy
      of PDT for tracing PPN connections and determining the organisation of these
      connections within the PPN in vivo, our observations suggest that diffusion
      tractography will be a useful new technique to rapidly identify connections in
      animal brains pre-mortem and post-mortem.

PMID- 19167230
TI  - Stress radiography and posterior pathological laxity of knee: comparison between
      two different techniques.
AB  - Stress radiographs have been recommended in order to obtain a better objective
      quantification of abnormal compartment knee motion. This tool has showed to be
      superior in quantifying a posterior cruciate ligament (PCL) lesion compared to
      clinical or arthrometer evaluation. Different radiographic techniques have been
      described in literature to quantify posterior pathological laxity. In this study
      we evaluated the total amount of posterior displacement (PTD) and side to side
      difference (SSD), before and after surgical reconstruction of PCL or PCL and
      posterolateral complex (PLC), using two different stress radiography techniques
      (Telos stress and kneeling view). Twenty patients were included in this study. We
      found a statistical significant difference about both total PTD and SSD among the
      two techniques preoperatively and at follow-up, with greatest values occurring
      using the kneeling view. Although stress radiographies has been introduced to
      allow an objective quantification of laxity in ligamentous injured knee, we
      believe that further studies on a large numbers of subjects are required to
      define the relationship between PTD values, measured with stress knee
      radiography, particularly using kneeling view, and ligamentous knee injury, in
      order to obtain a real useful tool in the decision making process, as well as to
      evaluate the outcome after ligamentous surgery.

PMID- 19167231
TI  - Different role of isoproterenol and NOS inhibitors on salivary ducts of rats.
AB  - OBJECTIVES: Nitric oxide (NO) is a diffusible intracellular messenger that is
      present in saliva. Chronic treatment with isoproterenol, a beta receptor agonist,
      stimulates the release of NO from acinar cells and induces salivary gland
      hypertrophy. The aim of this study was to investigate the effect of NO synthesis
      inhibitors and isoproterenol on rat salivary glands. We analyzed salivary gland
      weight and the number of ducts per unit area (0.5mm(2)) by NADPH-diaphorase
      histochemistry (to identify the presence of the enzyme NO synthase-NOS) and
      haematoxylin-and-eosin (HE). METHODS: For 8 days male Wistar rats received daily
      single intraperitoneal injections of saline or a NOS inhibitor (40mg/kg N(omega)
      nitro-L-arginine L-NOARG or N(omega)-nitro-l-arginine methyl ester L-NAME). This
      was followed, 30min later, by subcutaneous injection of isoproterenol (2 or
      5mg/kg) or saline. RESULTS: Isoproterenol increased parotid and submandibular
      gland weights. Isoproterenol (2mg/kg) induced a decrease of ducts per unit area
      inversely correlated to the weight of the parotid gland. This effect was
      augmented by L-NAME. In the submandibular gland L-NAME attenuated isoproterenol
      (2mg/kg) weight increase. In the submandibular gland isoproterenol and NOS
      inhibitors induced an increase in ducts per unit area (HE and NADPH-diaphorase).
      No effect was observed in the sublingual gland. CONCLUSION: To our knowledge this
      is the first description of isoproterenol and NOS inhibitors increasing duct
      density in the submandibular gland. Our results corroborate the hypothesis that
      NO plays different roles in parotid and submandibular glands.

PMID- 19167232
TI  - A new 18F-labelled derivative of the MMP inhibitor CGS 27023A for PET:
      radiosynthesis and initial small-animal PET studies.
AB  - The CGS 27023A derivative (R)-2-(N-((6-fluoropyridin-3-yl)methyl)-4-methoxyphenyl
      sulphonamido)-N-hydroxy-3-methylbutanamide 1a was identified as a very potent
      matrix metalloproteinase inhibitor. Here, we describe a one-step radiosynthesis
      of the target compound [(18)F]1a. The syntheses of [(18)F]1a resulted in a
      radiochemical yield of 12.1+/-5.9% (decay-corrected), a radiochemical purity of
      98.8+/-0.6%, and a specific activity of 39+/-27 GBq/micromol at the end of
      synthesis within 160+/-18 min from the end of radionuclide production (n=5).
      Initial small-animal PET studies in wild-type mice (C57/BL6) showed no
      unfavourable tissue accumulation of [(18)F]1a.

PMID- 19167233
TI  - Oxylipins: structurally diverse metabolites from fatty acid oxidation.
AB  - Oxylipins are lipophilic signaling molecules derived from the oxidation of
      polyunsaturated fatty acids. Initial fatty acid oxidation occurs mainly by the
      enzymatic or chemical formation of fatty acid hydroperoxides. An array of
      alternative reactions further converting fatty acid hydroperoxides gives rise to
      a multitude of oxylipin classes, many with reported signaling functions in
      plants. Oxylipins include the phytohormone, jasmonic acid, and a number of other
      molecules including hydroxy-, oxo- or keto-fatty acids or volatile aldehydes that
      may perform various biological roles as second messengers, messengers in inter
      organismic signaling, or even as bactericidal agents. The structural diversity of
      oxylipins is further increased by esterification of the compounds in plastidial
      glycolipids, for instance the Arabidopsides, or by conjugation of oxylipins to
      amino acids or other metabolites. The enzymes involved in oxylipin metabolism are
      diverse and comprise a multitude of examples with interesting and unusual
      catalytic properties. In addition, the interplay of different subcellular
      compartments during oxylipin biosynthesis suggests complex mechanisms of
      regulation that are not well understood. This review aims at giving an overview
      of plant oxylipins and the multitude of enzymes responsible for their
      biosynthesis.

PMID- 19167234
TI  - Primary right atrial cardiac osteosarcoma with congestive heart failure.
AB  - Right atrial cardiac osteosarcoma is a rare intracardiac tumor that can be
      difficult to diagnose. This report describes a 20-year-old man who was referred
      to our hospital with symptoms of heart failure. Echocardiography revealed a mass
      adhering to the right arterial septum that extended into the right ventricle and
      inferior vena cava. Right ventricular failure and worsening symptoms indicated
      the need for emergency life-saving surgery. Thereafter, the associated symptoms
      dramatically and rapidly diminished, and two days later the patient had recovered
      sufficiently to walk unaided. The short-term results of surgical tumor excision
      were excellent.

PMID- 19167235
TI  - Penetrating ulcer of the ascending aorta without rupture.
AB  - Penetrating ulcer of the ascending aorta is a very rare pathological entity with
      known potential for progression towards intramural hematoma or dissection.
      Intraoperative diagnosis of an asymptomatic ulcer of the ascending aorta was
      carried in a 60-year-old male with rheumatic valve disease. The tubular portion
      of the aorta was slightly dilated (45 mm) and the aortic valve was tricuspid. A
      supracoronary replacement of the ascending aorta was performed with a Dacron
      tube. Pathological analysis of the operative sample showed a considerable
      thinning of the aortic wall with a complete lack of elastic fibers at the level
      of the penetrating ulcer surrounded by a slightly dystrophic ascending aorta free
      from calcification and atheroma.

PMID- 19167236
TI  - Twenty seven-year experience with sternal cleft repair.
AB  - Congenital sternal cleft is a rare disease, and primary repair in the neonatal
      period is its best management. In 1998 we presented three surgical techniques for
      sternal cleft correction, but since 1999 we have elected one of them as our
      procedure of choice. Our latest results are now presented. It is a review of 15
      patients operated from October 1979 to December 2007. Surgical repair consisted
      of 3 sliding chondrotomies, 10 reconstructions based on a 'posterior sternal
      wall', 1 reconstruction combined to Ravitch operation for pectus excavatum and 1
      associated with total repair of Cantrell's pentalogy. Data concerning
      epidemiological features, surgical reconstruction, aesthetic results,
      postoperative major complications, mortality and hospital stay, were collected
      from hospital charts. Follow-up ranged from 4 months to 27 years. All patients
      submitted to surgical correction had a good aesthetic and functional result.
      Neither postoperative mortality nor major complication was observed. Two patients
      had subcutaneous fluid collection that prolonged the drainage duration. The mean
      hospital stay was 6 days. In conclusion, reconstructing sternal cleft with a
      'posterior periosteal flap from sternal bars and chondral graft' is an effective
      option with good aesthetic and long-term functional results.

PMID- 19167238
TI  - Erythropoietin augments the cytokine response to acute endotoxin-induced
      inflammation in humans.
AB  - Recent studies have shown that erythropoietin (EPO) offers protection against
      ischemia, hemorrhagic shock and systemic inflammation in many tissues and it has
      been suggested that EPO has anti-inflammatory effects. With the aim of
      investigating the potential acute anti-inflammatory effects of EPO in a human in
      vivo model of acute systemic low-grade inflammation, we measured circulating
      inflammatory mediators after intravenous administration of Escherichia coli
      endotoxin (LPS) bolus injection (0.1 ng/kg of body weight) in young healthy male
      subjects. The subjects were divided into three groups receiving either (1) LPS
      alone, (2) EPO alone (15,000 IE of rHuEPO) or (3) EPO and LPS. Endotoxin
      administration alone induced a 3-, 12- and 5-fold increase in plasma
      concentrations of TNF-alpha, IL-6 and IL-10, respectively, 3h after LPS
      challenge. When EPO was given prior to a bolus injection with endotoxin, the
      levels of TNF-alpha and IL-6 were enhanced by 5- and 40-fold, respectively,
      whereas the endotoxin-induced increase in IL-10 response was not influenced by
      EPO. In contrast to our hypothesis, we find that EPO augments the acute
      inflammatory effect.

PMID- 19167239
TI  - Management of subclavian arterial injuries following inadvertent arterial
      puncture during central venous catheter placement.
AB  - Subclavian artery injuries after central venous catheter placement constitute a
      rare but potentially fatal complication. In this case series, the authors
      describe several endovascular treatment options in the management of iatrogenic
      subclavian arterial injuries resulting from inadvertent arterial placement of
      central catheters.

PMID- 19167240
TI  - Embolization efficacy and treatment effectiveness of transarterial therapy for
      unresectable hepatocellular carcinoma: a case-controlled comparison of
      transarterial ethanol ablation with lipiodol-ethanol mixture versus transcatheter
      arterial chemoembolization.
AB  - PURPOSE: To compare the embolization efficacy and treatment effectiveness of
      transarterial ethanol ablation (TEA) versus those of chemoembolization and
      evaluate the correlation between embolization efficacy and treatment
      effectiveness of these treatments for hepatocellular carcinoma (HCC). MATERIALS
      AND METHODS: A case-controlled study was undertaken with 30 patients in each
      group matched based on Child-Pugh grade, tumor characteristics, and performance
      status. Primary endpoints were embolization efficacy (ie, Lipiodol retention
      within tumor at 2 months) and treatment effectiveness as evaluated by tumor
      response, disease progression, progression-free survival, and overall survival.
      The secondary endpoint was correlation between embolization efficacy and
      treatment effectiveness. RESULTS: Lipiodol retention was greater in the TEA group
      (89.5% +/- 10.7% vs 47.5% +/- 21.2%; P < .0001). The tumor progression rate at 1
      year was higher in the chemoembolization group (five of 30 vs zero of 30; P =
      .0261). One- and 2-year overall survival rates were higher in the TEA group
      (93.3% and 80.0%, respectively, vs 73.3% and 43.3%, respectively; P = .0053). One
      and 2-year extrahepatic disease progression rates were lower in the TEA group (P
      = .0002). There were no differences in progression-free survival and intrahepatic
      disease progression rates at 1 and 2 years. Patients with greater Lipiodol
      retention (ie, >60%) had better treatment outcomes at 1 year than those with
      lesser retention, with higher overall survival rates (88.9% vs 66.7%; P = .0192),
      lower intrahepatic disease progression rates (25.6% vs 59.4%; P = .0169), lower
      extrahepatic disease progression rates (0.31% vs 35.5%; P = .0047), and higher
      progression-free survival rates (72.1% vs 36.3%; P = .005). CONCLUSIONS: The
      embolization efficacy and treatment effectiveness of TEA are probably superior to
      those of chemoembolization for HCC.

PMID- 19167241
TI  - Migration of an ingested foreign body into the right external iliac vein.

PMID- 19167242
TI  - Stent implantation of multichanneled pseudoocclusion of the internal carotid
      artery.
AB  - Multichanneled pseudoocclusion (MCPO) is a severe stenosis with more than 95% of
      the carotid bulb with multichannels in the stenotic segment. This report
      describes successful carotid stent implantation in five patients with MCPO of the
      internal carotid artery. Probing of the micro-guide wire through the channel with
      support of the microcatheter made subsequent angioplasty and stent placement
      possible without procedure-related complications. There was neither additional
      stroke nor restenosis during a follow-up period of 6-54 months.

PMID- 19167243
TI  - Technical aspects of imaging and transfemoral arterial treatment of N1-S1 tumors
      in rats: an appropriate model to test the biology and therapeutic response to
      transarterial treatments of liver cancers.
AB  - The present study was undertaken to assess the technical feasibility of
      transfemoral hepatic artery catheterization in rats and to describe the imaging
      techniques that can be used on tumors in rats. A total of 106 N1-S1 cells were
      inoculated into the left lobes of 74 rats. In 17, transfemoral angiography was
      attempted. Tumor volumes for 2 weeks before angiography were measured with
      magnetic resonance imaging in 40 animals. Tumors grew in 63 animals. Angiography
      was successful in 16 rats. Mean tumor volumes were 0.13 mL and 0.9 mL after 1 and
      2 weeks, respectively. In conclusion, transfemoral hepatic artery catheterization
      is feasible in this animal model.

PMID- 19167244
TI  - Establishment of the radiation effect of yttrium-90 microspheres: role of C-arm
      CT.

PMID- 19167245
TI  - Salvage therapy for liver-dominant colorectal metastatic adenocarcinoma:
      comparison between transcatheter arterial chemoembolization versus yttrium-90
      radioembolization.
AB  - PURPOSE: To compare transarterial chemoembolization (CE) versus yttrium-90
      ((90)Y) radioembolization (RE) for liver-dominant metastatic colorectal
      adenocarcinoma as salvage therapy. MATERIALS AND METHODS: Of 36 patients, 21
      underwent CE (37 procedures; 11 men; mean age, 67 years; 16 with Child-Pugh class
      A disease) and 15 underwent (90)Y RE (19 procedures; 11 men; mean age, 64 years;
      13 with Child-Pugh class A disease) for liver-dominant colorectal adenocarcinoma.
      Mean index dominant lesion sizes were 9.3 cm and 8.2 cm in the CE and RE groups,
      respectively. Multilobar disease was seen in 67% and 87% of the respective
      groups, and extrahepatic metastases were seen in 43% and 33%, respectively. Mean
      times from diagnosis of liver metastasis to CE or RE were 17.6 months and 22.6
      months, respectively. RESULTS: A total of 37 CE procedures with cisplatin,
      doxorubicin, and mitomycin were performed, and 19 RE procedures with (90)Y were
      performed; 43% of patients in the CE group and 20% in the RE group received
      multiple treatment sessions, and 100% of procedures were technically successful.
      Median survival times were 7.7 months for the CE group and 6.9 months for the RE
      group (P = .27). The 1-, 2-, and 5-year survival rates were 43%, 10%, and 0%,
      respectively, in the CE group; and 34%, 18%, and 0%, respectively, in the RE
      group. There was one major complication (2.7%) in the CE group (pulmonary
      embolism), with a 30-day mortality rate of 5.4% (n = 2). There were no major
      complications in the RE group, with a 30-day mortality rate of 5.2% (n = 1).
      CONCLUSIONS: Patients with unresectable liver colorectal metastases that progress
      despite systemic chemotherapy can undergo palliative treatment with CE or RE with
      similar survival benefit.

PMID- 19167246
TI  - Fatal nontarget embolization via an intrafibroid arterial venous fistula during
      uterine fibroid embolization.

PMID- 19167247
TI  - Two cases of needle-tract seeding after percutaneous radiofrequency ablation for
      lung cancer.
AB  - The authors describe two cases of needle-tract seeding after percutaneous
      radiofrequency (RF) ablation for lung cancer. Needle biopsy was performed
      immediately before RF ablation in one case. In both cases, RF ablation was
      performed with a single internally cooled electrode, which was removed without
      cauterizing the electrode tract. The seeding nodule appeared 4 or 7 months after
      RF ablation and was then completely treated with a repeat RF ablation.

PMID- 19167248
TI  - Behavior of parasite-specific effector CD8+ T cells in the brain and
      visualization of a kinesis-associated system of reticular fibers.
AB  - To understand lymphocyte behavior in the brain, we used two-photon microscopy to
      visualize effector CD8(+) T cells during toxoplasmic encephalitis. These cells
      displayed multiple behaviors with two distinct populations of cells apparent: one
      with a constrained pattern of migration and one with a highly migratory subset.
      The proportion of these populations varied over time associated with changes in
      antigen availability as well as T cell expression of the inhibitory receptor PD1.
      Unexpectedly, the movement of infiltrating cells was closely associated with an
      infection-induced reticular system of fibers. This observation suggests that,
      whereas in other tissues pre-existing scaffolds exist that guide lymphocyte
      migration, in the brain specialized structures are induced by inflammation that
      guide migration of T cells in this immune-privileged environment.

PMID- 19167249
TI  - The shaping of T cell receptor recognition by self-tolerance.
AB  - During selection of the T cell repertoire, the immune system navigates the subtle
      distinction between self-restriction and self-tolerance, yet how this is achieved
      is unclear. Here we describe how self-tolerance toward a trans-HLA (human
      leukocyte antigen) allotype shapes T cell receptor (TCR) recognition of an
      Epstein-Barr virus (EBV) determinant (FLRGRAYGL). The recognition of HLA-B8
      FLRGRAYGL by two archetypal TCRs was compared. One was a publicly selected TCR,
      LC13, that is alloreactive with HLA-B44; the other, CF34, lacks HLA-B44
      reactivity because it arises when HLA-B44 is coinherited in trans with HLA-B8.
      Whereas the alloreactive LC13 TCR docked at the C terminus of HLA-B8-FLRGRAYGL,
      the CF34 TCR docked at the N terminus of HLA-B8-FLRGRAYGL, which coincided with a
      polymorphic region between HLA-B8 and HLA-B44. The markedly contrasting
      footprints of the LC13 and CF34 TCRs provided a portrait of how self-tolerance
      shapes the specificity of TCRs selected into the immune repertoire.

PMID- 19167250
TI  - Promising results of the chaperone effect caused by imino sugars and
      aminocyclitol derivatives on mutant glucocerebrosidases causing Gaucher disease.
AB  - Gaucher disease is an autosomal recessive disorder. It is characterized by the
      accumulation of glucosylceramide in lysosomes of mononuclear phagocyte system,
      attributable to acid beta-glucosidase deficiency. The main consequences of this
      disease are hepatosplenomegaly, skeletal lesions and, sometimes, neurological
      manifestations. At sub-inhibitory concentrations, several competitive inhibitors
      act as chemical chaperones by inducing protein stabilization and increasing
      enzymatic activity. Here we tested two iminosugars (NB-DNJ and NN-DNJ) and four
      aminocyclitols with distinct degrees of lipophilicity as pharmacological
      chaperones for glucocerebrosidase (GBA). We report an increase in the activity of
      GBA using NN-DNJ, NB-DNJ and aminocyclitol 1 in stably transfected cell lines,
      and an increment with NN-DNJ and aminocyclitol 4 in patient fibroblasts. These
      results on specific mutations validate the use of chemical chaperones as a
      therapeutic approach for Gaucher disease. However, the development and analysis
      of new compounds is required in order to find more effective therapeutic agents
      that are active on a broader range of mutations.

PMID- 19167251
TI  - Brain injury in glutaric aciduria type I: the value of functional techniques in
      magnetic resonance imaging.
AB  - BACKGROUND: Acute striatal necrosis is a devastating consequence of
      encephalopathic crisis in patients with glutaric aciduria type I (GA-I), but the
      mechanisms underlying brain injury are not completely understood. OBJECTIVE: To
      approach pathophysiological aspects of brain injury in GA-I by means of
      functional techniques in magnetic resonance imaging (MRI). PATIENTS AND METHODS:
      Four patients during an acute encephalopathic crisis and three asymptomatic
      siblings with GA-I underwent single-voxel hydrogen magnetic resonance
      spectroscopy (MRS) and brain MRI including gradient echo T1-weighted, FLAIR, T2
      weighted and diffusion-weighted imaging. RESULTS: The study was performed between
      three and eight days after the onset of acute encephalopathic crisis. Isotropic
      diffusion images showed high signal changes with corresponding low apparent
      diffusion coefficient values within the putamen, caudate nuclei and globus
      pallidus (four patients), and the cerebral peduncles including the substantia
      nigra (one patient). The study disclosed normal findings in asymptomatic
      siblings. MRS showed decreased N-acetyl-aspartate/creatine ratio at the basal
      ganglia in encephalopathic patients when compared to a group of sex- and age
      matched controls. CONCLUSIONS: Brain injury in GA-I is characterized by the
      presence of cytotoxic edema and reduced neuronal integrity by functional imaging
      techniques. Involvement of the basal ganglia may be asymmetrical in patients with
      unilateral motor disorder and may extent to the cerebral peduncles and substantia
      nigra, which may be responsible for the acute onset dystonia in some patients.
      Functional techniques failed to demonstrate any abnormalities in asymptomatic
      patients, which is in agreement with the integrity of basal ganglia structures
      observed by conventional MRI sequences.

PMID- 19167252
TI  - High post surgical opioid requirements in Crohn's disease are not due to a
      general change in pain sensitivity.
AB  - Crohn's disease (CD) is a painful inflammatory bowel disease with complex
      multigenic inheritance. Suggested on the basis of a few isolated reports CD
      patients require significantly higher post operative opioid doses than patients
      undergoing comparable severe abdominal surgery. Crohn's disease therefore may be
      a suitable model for the identification of novel pain susceptibility genes. In
      order to confirm this observation and to elucidate the underlying molecular
      mechanisms, we investigated if higher opioid needs of CD patients are due to a
      general change in pain sensitivity. Quantitative sensory testing (QST) was
      applied to a subgroup of patients and polymorphisms in the mu-opioid receptor
      (OPRM1) and catechol-O-methyltransferase (COMT) were investigated. Significantly
      increased post operative opioid requirements in CD patients were confirmed and
      QST assessment demonstrates that CD patients do not display increased pain
      sensitivity in terms of lowered thresholds to thermal and mechanical stimuli. The
      data also suggest that common variants in OPRM1 and specific 'high pain
      sensitivity'COMT haplotypes may not be the cause of high opioid needs. The
      results indicate that a more complex pathway is involved in the greater post
      operative opioid demand in CD. Therefore the presence of other, as yet unknown,
      genes could modulate opioid requirements in CD patients.

PMID- 19167253
TI  - Coulomb energies of protein-protein complexes with monopole-free charge
      distributions.
AB  - From an analysis of Coulomb energy distributions of a large set of protein
      protein complexes we show that the positive tail in the energy distribution
      disappears when the monopole-monopole term, the only energy term independent of
      inter-subunit orientations, is removed. This indicates that unfavorable Coulomb
      energies associated with subunit orientations are excluded in protein-protein
      complexes. The overall result remained unchanged when solvent effects were
      included. Our results have important bearing on the restriction of subunit
      orientations in protein-protein complexes and complement a recent work [K. Brock,
      K. Talley, K. Coley, P. Kundrotas, E. Alexov, Optimization of electrostatic
      interactions in protein-protein complexes, Biophys. J. 93 (2007) 3340-3352.]
      which showed that Coulomb energy of interaction in protein-protein complexes is
      sequence-optimized.

PMID- 19167254
TI  - Molecular modeling of the heterodimer of human CFTR's nucleotide-binding domains
      using a protein-protein docking approach.
AB  - We have presented a new protein-protein docking approach to model heterodimeric
      structures based on the conformations of the monomeric units. The conventional
      modeling method relies on superimposing two monomeric structures onto the crystal
      structure of a homologous protein dimer. The resulting structure may exhibit
      severe backbone clashes at the dimeric interface depending on the backbone
      dissimilarity between the target and template proteins. Our method overcomes the
      backbone clashing problem and requires no a priori knowledge of the dimeric
      structure of a homologous protein. Here we used human Cystic Fibrosis
      Transmembrane conductance Regulator (CFTR), a chloride channel whose dysfunction
      causes cystic fibrosis, for illustration. The two intracellular nucleotide
      binding domains (NBDs) of CFTR control the opening and closing of the channel.
      Yet, the structure of the CFTR's NBD1-NBD2 complex has not been experimentally
      determined. Thus, correct modeling of this heterodimeric structure is valuable
      for understanding CFTR functions and would have potential applications for drug
      design for cystic fibrosis treatment. Based on the crystal structure of human
      CFTR's NBD1, we constructed a model of the NBD1-NBD2 complex. The constructed
      model is consistent with the dimeric mode observed in the crystal structures of
      other ABC transporters. To verify our structural model, an ATP substrate was
      docked into the nucleotide-binding site. The predicted binding mode shows
      consistency with related crystallographic findings and CFTR functional studies.
      Finally, genistein, an agent that enhances CFTR activity, though the mechanism
      for such enhancement is unclear, was docked to the model. Our predictions agreed
      with genistein's bell-shaped dose-response relationship. Potential mutagenesis
      experiments were proposed for understanding the potentiation mechanism of
      genistein and for providing insightful information for drug design targeting at
      CFTR. The method used in this study can be applied to modeling studies of other
      dimeric protein structures.

PMID- 19167255
TI  - Rapid screening for nuclear genes mutations in isolated respiratory chain complex
      I defects.
AB  - Complex I or reduced nicotinamide adenine dinucleotide (NADH): ubiquinone
      oxydoreductase deficiency is the most common cause of respiratory chain defects.
      Molecular bases of complex I deficiencies are rarely identified because of the
      dual genetic origin of this multi-enzymatic complex (nuclear DNA and
      mitochondrial DNA) and the lack of phenotype-genotype correlation. We used a
      rapid method to screen patients with isolated complex I deficiencies for nuclear
      genes mutations by Surveyor nuclease digestion of cDNAs. Eight complex I nuclear
      genes, among the most frequently mutated (NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS7,
      NDUFS8, NDUFV1 and NDUFV2), were studied in 22 cDNA fragments spanning their
      coding sequences in 8 patients with a biochemically proved complex I deficiency.
      Single nucleotide polymorphisms and missense mutations were detected in 18.7% of
      the cDNA fragments by Surveyor nuclease treatment. Molecular defects were
      detected in 3 patients. Surveyor nuclease screening is a reliable method for
      genotyping nuclear complex I deficiencies, easy to interpret, and limits the
      number of sequence reactions. Its use will enhance the possibility of prenatal
      diagnosis and help us for a better understanding of complex I molecular defects.

PMID- 19167256
TI  - Murine muscle cell models for Pompe disease and their use in studying therapeutic
      approaches.
AB  - Lysosomes filled with glycogen are a major pathologic feature of Pompe disease, a
      fatal myopathy and cardiomyopathy caused by a deficiency of the glycogen
      degrading lysosomal enzyme, acid alpha-glucosidase (GAA). To facilitate studies
      germane to this genetic disorder, we developed two in vitro Pompe models:
      myotubes derived from cultured primary myoblasts isolated from Pompe (GAA KO)
      mice, and myotubes derived from primary myoblasts of the same genotype that had
      been transduced with cyclin-dependent kinase 4 (CDK4). This latter model is
      endowed with extended proliferative capacity. Both models showed extremely large
      alkalinized, glycogen-filled lysosomes as well as impaired trafficking to
      lysosomes. Although both Pompe tissue culture models were derived from fast
      muscles and were fast myosin positive, they strongly resemble slow fibers in
      terms of their pathologic phenotype and their response to therapy with
      recombinant human GAA (rhGAA). Autophagic buildup, a hallmark of Pompe disease in
      fast muscle fibers, was absent, but basal autophagy was functional. To evaluate
      substrate deprivation as a strategy to prevent the accumulation of lysosomal
      glycogen, we knocked down Atg7, a gene essential for autophagosome formation, via
      siRNA, but we observed no effect on the extent of glycogen accumulation, thus
      confirming our recent observation in autophagy-deficient Pompe mice [N. Raben, V.
      Hill, L. Shea, S. Takikita, R. Baum, N. Mizushima, E. Ralston, P. Plotz,
      Suppression of autophagy in skeletal muscle uncovers the accumulation of
      ubiquitinated proteins and their potential role in muscle damage in Pompe
      disease, Hum. Mol. Genet. 17 (2008) 3897-3908] that macroautophagy is not the
      major route of glycogen transport to lysosomes. The in vitro Pompe models should
      be useful in addressing fundamental questions regarding the pathway of glycogen
      to the lysosomes and testing panels of small molecules that could affect glycogen
      biosynthesis or speed delivery of the replacement enzyme to affected lysosomes.

PMID- 19167257
TI  - Diltiazem, a L-type Ca(2+) channel blocker, also acts as a pharmacological
      chaperone in Gaucher patient cells.
AB  - Recently, inhibition of L-type Ca(2+) channels, using either Diltiazem or
      Verapamil, has been reported to partially restore mutant glucocerebrosidase
      activity in cells from patients with Gaucher disease homozygous for the N370S or
      L444P alleles, as well as cells from patients with two other lysosomal storage
      diseases. It was hypothesized that these drugs act on the endoplasmic reticulum,
      increasing its folding efficiency, inhibited due to altered calcium homeostasis.
      Several other laboratories have reported that cells carrying either the N370S or
      the F213I alleles are amenable to enzyme enhancement therapy with pharmacological
      chaperones, whereas cells homozygous for L444P respond poorly. We found that
      Verapamil treatment does not enhance mutant enzyme activity in any of the cell
      lines tested, while Diltiazem moderately increases activity in normal cells, and
      in N370S/N370S and F213I/L444P, but not in L444P/L444P Gaucher cells, or in
      either of two adult Tay-Sachs disease cell lines. Since the mode of action of
      pharmacological chaperones and Diltiazem are believed to be different, we
      examined the possibility that they could act in concert. Diltiazem co
      administered with known chaperones failed to increase enzyme activities above
      that reached by chaperone-treatment alone in any of the patient cell lines. Thus,
      we re-examined the possibility that Diltiazem acts as a pharmacological
      chaperone. We found that, at the acidic pH of lysosomes, Diltiazem was not an
      inhibitor, nor did its presence increase the heat stability of
      glucocerebrosidase. However, at neutral pH, found in the endoplasmic reticulum,
      Diltiazem exhibited both of these properties. Thus Diltiazem exhibits the
      biochemical characteristics of a glucocerebrosidase pharmacological chaperone.

PMID- 19167258
TI  - [Radiotherapy of maxillary sinus carcinoma: state of art].
AB  - Maxillary sinus carcinomas are rare malignancies of the face, characterized by
      high local relapsing rate. Modalities of treatment are without consensus and
      respective roles of radiation therapy and surgery remain controversial. As those
      malignancies are often diagnosed at locally advanced stage, radiation therapy may
      frequently be used for patients having unresectable advanced disease.
      Nevertheless, surgery remains treatment of choice for more localized
      malignancies, in association with systematic postoperative radiotherapy. For
      those patients whose prognosis remains pejorative, it is necessary to precise the
      role of radiotherapy in first intention for inoperable tumors, to define
      necessity for nodal treatment performing and evaluate the place of neoadjuvant or
      concomitant chemotherapy in a multimodal strategy.

PMID- 19167259
TI  - Pharmacologic treatment of advanced Parkinson's disease: a meta-analysis of COMT
      inhibitors and MAO-B inhibitors.
AB  - OBJECTIVE: To perform a meta-analysis of randomized placebo-controlled trials
      evaluating catechol-O-methyltransferase (COMT) inhibitors or monoamine oxidase
      type B (MAO-B) inhibitors in addition to levodopa versus levodopa alone for the
      treatment of advanced Parkinson's disease (PD). METHODS: A systematic literature
      search was performed between 1990 and October 2007. The primary outcome measures
      assessed were the reduction in scores of Unified Parkinson's Disease Rating Scale
      (UPDRS) total, activities of daily living (ADL) and motor scores from baseline.
      Other efficacy and safety endpoints were also evaluated. RESULTS: A total of 13
      trials (n=3775 subjects) were included in the meta-analysis. As compared to
      placebo, COMT and MAO-B inhibitor use resulted in greater improvement in UPDRS
      total score (weighted mean difference [WMD] -2.13, 95%CI -0.46 to -0.20; and WMD 
      5.03, 95%CI -7.38 to -2.68) ADL scores (WMD -0.99, 95%CI -1.56 to -0.43; and WMD 
      1.48, 95%CI -2.13 to -0.83) and motor scores (WMD -1.50, 95%CI -2.70 to -0.30;
      and WMD -3.19, 95%CI -4.57 to -1.80) as well as increase in "on" time, reduction
      in "off" time and decreased need in levodopa dose compared to placebo. Incidences
      of dyskinesia were significantly higher with the COMT and MAO-B inhibitors
      compared to placebo. CONCLUSION: The use of COMT or MAO-B inhibitors plus
      levodopa is superior to levodopa alone at reducing PD symptoms in patients with
      advanced PD. While combination therapies with COMT or MAO-B inhibitor plus
      levodopa seem especially useful amongst PD patients with wearing-off phenomenon,
      they are associated with more adverse events.

PMID- 19167260
TI  - Evolution of root endosymbiosis with bacteria: How novel are nodules?
AB  - Plants form diverse symbioses with nitrogen-fixing bacteria to gain access to
      ammonium, a product of the prokaryote-exclusive enzyme nitrogenase. Improving the
      symbiotic effectiveness of crop plants like maize, wheat or rice is a highly
      topical challenge and could help reduce the need for energy-intense nitrogen
      fertilizer in staple food production. Root nodule symbiosis (RNS) constitutes one
      of the most productive nitrogen-fixing systems, but it is restricted to a small
      group of related angiosperms. Here, we review the genetic regulation of RNS and
      its interconnections with other plant symbiosis or plant developmental programs.
      Since RNS uses genetic programs that are widely conserved in land plants, we
      evaluate the prospects for a transfer to plants that are currently non
      nodulating.

PMID- 19167261
TI  - Simplified recording of soft contact lens fit.
AB  - PURPOSE: To determine the critical fitting characteristics of modern soft contact
      lens fits and from this to devise a simplified recording scheme. METHODS: Ten
      subjects (aged 28.1+/-7.4 years) wore eight different modern soft contact lenses.
      Video was captured and analysed of blink (central and up-gaze), excursion lag
      (up, down, right and left gaze) and push-up movement, centration and coverage.
      RESULTS: Lens centration was on average close to the corneal centre. Movement on
      blink was significantly smaller in up-gaze than in primary-gaze (p<0.001). Lag
      was greatest in down-gaze and least in up-gaze (p<0.001). Push-up test recovery
      speed was 1.32+/-0.73 mm/s. Overall lens movement was determined best by
      assessing horizontal lag, movement on blink in up-gaze and push-up recovery
      speed. Steeper lens base-curves did not have a significant effect on lens fit
      characteristics. Contact lens material did influence lens fit characteristics,
      particularly silicone-hydrogels which generally had lower centration and a faster
      push-up speed of recovery than HEMA lenses (p<0.05). CONCLUSION: Lag on vertical
      gaze, and movement on blink in primary gaze generally provide little extra
      information on overall lens movement compared to horizontal lag, movement on
      blink in up-gaze and push-up recovery speed. They can therefore be excluded from
      a simplified recording scheme. A simplified and comprehensive soft contact lens
      fit recording system could consist of a cross-hairs indicating the centre of the
      cornea; a circle to indicate the lens centration; a mark on the relevant position
      of the circle to indicate any limbal incursion; a grade (B) below for movement
      with blink in up-gaze, a grade (L) to the side for horizontal lag and a grade
      above (P) for the assessed push-up recovery speed.

PMID- 19167262
TI  - How often are contact lenses worn?
AB  - There are important clinical, academic and commercial reasons for seeking to
      develop a comprehensive understanding of the frequency of wear of different forms
      of contact lenses. Data that we have gathered from annual contact lens fitting
      surveys over the past 12 years demonstrate that contact lenses are worn, on
      average, 5.4+/-1.9 days per week. Rigid lenses tended to be worn on a full-time
      basis, typically seven days per week. The distribution of daily disposable lens
      wear is bimodal, with peaks at two days and seven days per week of wear. Over the
      survey period there appears to have been a small trend toward the use of contact
      lenses on a part-time basis.

PMID- 19167263
TI  - Infrared optical constants, dielectric constants, molar polarizabilities,
      transition moments, dipole moment derivatives and Raman spectrum of liquid
      cyclohexane.
AB  - Previous studies have been done in this laboratory focusing on the optical
      properties of several liquid aromatic and aliphatic hydrocarbons in the infrared.
      The current study reports the infrared and absorption Raman spectra of liquid
      cyclohexane. Infrared spectra were recorded at 25 degrees C over a wavenumber
      range of 7400-490 cm(-1). Infrared measurements were taken using transmission
      cells with pathlengths ranging from 3 to 5000 microm. Raman spectra were recorded
      between 3700 and 100 cm(-1) at 25 degrees C using a 180 degrees reflection
      geometry. Ab initio calculations of the vibrational wavenumbers at the
      B3LYP/6311G level of theory were performed and used to help assign the observed
      IR and Raman spectra. Extensive assignments of the fundamentals and binary
      combinations observed in the infrared imaginary molar polarizability spectrum are
      reported. The imaginary molar polarizability spectrum was curve fitted to
      separate the intensity from the various transitions and used to determine the
      transition moments and magnitudes of the derivatives of the dipole moment with
      respect to the normal coordinates for the fundamentals.

PMID- 19167264
TI  - Tlapallite H(6)(Ca,Pb)(2)(Cu,Zn)(3)SO(4)(TeO(3))(4)TeO(6), a multi-anion mineral:
      A Raman spectroscopic study.
AB  - Tellurates may be subdivided according to formula and structure. There are three
      types of tellurate minerals: type (a) (AB)(m)(TeO(4))(p)Z(q), type (b)
      (AB)(m)(TeO(6)).xH(2)O and type (c), compound tellurates in which a second anion
      is involved. Tlapallite, a multi-anion mineral containing both tellurate and
      tellurite units, as well as sulphate, is an example of type (a). Tellurates are
      rare minerals as the tellurate ion is easily reduced to the tellurite ion. Raman
      bands at 691, 708, 764 and 796cm(-1) are attributed to (TeO(6))(2-) and
      (TeO(3))(2-) stretching bands. The intense sharp Raman band at 973cm(-1) is
      assigned to the nu(1) (SO(4))(2-) symmetric stretching mode, whilst the two bands
      at 1062 and 1104cm(-1) are assigned to the nu(3) (SO(4))(2-) antisymmetric
      stretching mode. The spectral region 100 to 600cm(-1) displays the bands which
      are attributable to the (SO(4))(2), (TeO(3))(2-) and (TeO(6))(4-) bending modes.
      Some evidence from very low intensity Raman bands in the 2800-3600cm(-1) region
      provides evidence of proton-tellurate/tellurite anion interactions.

PMID- 19167265
TI  - Infrared and near-infrared spectroscopic study of synthetic hydrotalcites with
      variable divalent/trivalent cationic ratios.
AB  - Near-infrared (NIR), X-ray diffraction (XRD) and infrared (IR) spectroscopy have
      been applied to hydrotalcites of the formula Mg(6)
      (Fe,Al)(2)(OH)(16)(CO(3)).4H(2)O formed by intercalation with the carbonate anion
      as a function of divalent/trivalent cationic ratio. Such hydrotalcites were found
      to show variation in the d-spacing attributed to the size of the cation. In the
      IR (1750-4000cm(-1)), the position of all bands except those at approximately
      3060cm(-1) shift to higher wavenumbers as the cation ratio increases. Conversely,
      at wavenumbers below 1000cm(-1), the bands shift to lower wavenumbers as the
      cation ratio increases. A water bending mode at higher wavenumbers was also
      observed which indicates that the water is strongly hydrogen bonded. In the NIR
      spectrum between 8000 and 12,000cm(-1), there is a broad feature which is
      attributed to electronic bands of the ferrous ion and low intensity sharp bands
      due to overtones of the OH stretching vibrations. It is also apparent from this
      region that Fe(2+) substitutes for Mg(2+). The intensity of bands at 7750 and
      5200cm(-1) increases as the cation ratio increases in the NIR spectrum.
      Hydrotalcites with a magnesium amount 3 and 4 times greater than that of
      aluminium and iron combined, in the lower wavenumber region of the NIR spectrum,
      have very similar spectral profiles. This work has shown that hydrotalcites with
      different divalent/trivalent ratios can be synthesised and characterised by
      infrared spectroscopy.

PMID- 19167266
TI  - Selective determination of ertapenem in the presence of its degradation product.
AB  - Stability-indicative determination of ertapenem (ERTM) in the presence of its
      beta-lactam open-ring degradation product, which is also the metabolite, is
      investigated. The degradation product has been isolated, via acid-degradation,
      characterized and elucidated. Selective quantification of ERTM, singly in bulk
      form, pharmaceutical formulations and/or in the presence of its major degradant
      is demonstrated. The indication of stability has been undertaken under conditions
      likely to be expected at normal storage conditions. Among the spectrophotometric
      methods adopted for quantification are first derivative ((1)D), first derivative
      of ratio spectra ((1)DD) and bivariate analysis.

PMID- 19167267
TI  - Novel homo-bimetallic complexes of [N(10)] macrocyclic ligand modified with
      tetrapeptide function: biological activities, spectral and cyclic voltammetric
      studies.
AB  - The bimetallic complexes [M(2)LCl(4)] (M=Cr, Co, Ni, Cu) prepared via metal
      template cyclization reactions were characterized by physico-chemical and
      spectroscopic methods. L is a 30-membered [N(10)] macrocycle with tetraamide
      functions bind metal ions through aza donors forming hexa-coordinate geometry.
      The perspective view and important structural parameters have been computed from
      the molecular model (MOPAC) method. The electrochemical studies indicate
      existence of quasi-reversible redox couples in solution. The metal complexes were
      screened (in vitro) against a few pathogenic fungi and bacteria to assess their
      growth inhibiting potential.

PMID- 19167268
TI  - Synthesis and structure of dimeric anthracene-9-carboxylato bridged dinuclear
      erbium(III) complex, [Er(2)(9-AC)(6)(DMF)(2)(H(2)O)(2)].
AB  - We study the influence of the bulky aromatic rings, e.g. anthracence-9-carboxylic
      acid (9-ACA) with a large conjugated pi-system on the structure and spectroscopic
      properties of [Er(2)(9-AC)(6)(DMF)(2)(H(2)O)(2)] complex where 9-AC=anthracence-9
      carboxylato and DMF=N,N'-dimethylformamide. The complex has been prepared from
      the erbium chloride and 9-ACA in the mixture of H(2)O:DMF solution (4:1, v/v)
      followed by pH adjustment to 6. The complex is crystallized in a monoclinic
      system with space group P2(1)/n. The two Er(III) ions are double bridged by the
      deprotonated carboxyl groups of two 9-AC anions (O1 and O1A), forming an eight
      coordination number. The chelating bidentate (O,O), chelating-bridging tridentate
      (O,O,O') and monodentate of 9-AC anions are observed in the dinuclear [Er(2)(9
      AC)(6)(DMF)(2)(H(2)O)(2)] complex. The Er-Er distance is 4.015A in the dimeric
      unit. Intramolecular O-Hcdots, three dots, centeredO and C-Hcdots, three dots,
      centeredO hydrogen bonds as well as numerous of intermolecular C-Hcdots, three
      dots, centeredpi interactions between the anthracene rings by edge-to-face
      interactions linked the dinuclear dimeric units into two-dimensional
      supramolecular network in a propeller-arrangement. Electronic absorption spectra
      of the Er(III) complex and its salt were measured. The emission spectrum of the
      complex is composed of a broad band due to the emission of intraligand pi*-->pi
      transition from the 9-AC anions and a shoulder peak originating from the 4f-4f
      emission transition of the Er(III) ions. The complex has a high thermal stability
      which can be attributed to the effectively increase the rigidity of the 9-AC
      anions.

PMID- 19167269
TI  - A vibrational study of the nature of hydroxyl groups chemical bonding in two
      aluminium hydroxides.
AB  - Lengths, strengths and valences of OH bonds in the two aluminium hydroxides
      gibbsite and bayerite were determined on the basis of vibrational spectral data.
      The uncoupled OD stretching modes in the range 2400-2800cm(-1) were recorded by
      means of infrared diffuse reflectance, thereby avoiding effects of surface,
      vibrational coupling or particle shape. The assignment of the corresponding Raman
      spectra resulted in the determination of harmonic wavenumbers, force constants
      and anharmonicity coefficients of bulk OH groups in the two minerals. OH bond
      lengths deduced from these data varied from 0.964A to 0.975A in gibbsite and
      0.962A to 0.973A in bayerite. These lengths appear to correspond to weak H-bonds
      contrary to previously recognized data from X-ray diffraction and neutron
      diffraction studies. Finally, bond valences were calculated on the basis of these
      new bond lengths and discussed as a function of crystallographic structures and
      the nature of hydrogen bonding in these two structures.

PMID- 19167270
TI  - Spectroscopic investigation of S-Ag interaction in omega-mercaptoundecanoic acid
      capped silver nanoparticles.
AB  - This paper deals with the synthesis of omega-mercaptoundecanoic acid (MUA) capped
      silver nanoparticles (NPs) with an average size of 15nm by citrate reduction
      technique and spectroscopic investigation of S-Ag interaction. We have studied
      the interaction of thiol with silver NPs in aqueous medium by employing UV-vis,
      Raman, FT-IR, and photoluminescence spectroscopy. The shifting of silver surface
      plasmon band in the UV-vis spectra shows the stabilization of the silver
      nanoparticles by MUA. The disappearance of S-H stretching in both the FT-IR and
      Raman spectra and the shifting of the NMR signals of the protons in close
      proximity to the metal center supported the existence of the S-Ag interaction in
      MUA capped silver NPs. The morphology of the thiol protected silver NPs was
      investigated by transmission electron microscopy (TEM) and was found to be
      distinct and spherical entities.

PMID- 19167271
TI  - Mobile healthcare services in school-based health center.
AB  - OBJECTIVES: In Taiwan, campus health problems are placing more and more pressure
      on school-based health centers (SBHCs). Moreover, SBHCs have insufficient
      resources to actively provide follow-up healthcare for students and faculty found
      to be overweight, chronically ill, or at high risk. In order to improve the
      quality of SBHC healthcare, a project was begun to enhance the efficiency of
      campus healthcare services by employing web-based and cell phone-based services.
      This project employed the Mobile Automated Medical Alert (MAMA) system, which was
      designed especially for campus health center use. Before implementing the MAMA
      system, a focus group of healthcare related staff identified areas in which SBHC
      healthcare services might be improved by the system and created a questionnaire
      to measure student and faculty response to the proposed services. Modifications
      to the MAMA design and service offerings were made based upon these questionnaire
      results. METHOD: After the initial brainstorming session, the MAMA team created a
      survey instrument that was administered to students and faculty in order to
      understand their attitudes toward the proposed mobile healthcare services. Two
      hundred questionnaires were distributed to students and faculty at a private
      technical college in central Taiwan. RESULTS: Among the respondents, 100% had
      cellular phones and used short-text messages. Ninety-five percent of the student
      respondents and 85% of the faculty respondents agreed that mobile healthcare
      system would improve the quality of the health care their SBHC was currently
      providing. Based on these positive survey responses, the MAMA system was
      implemented. DISCUSSION/CONCLUSION: The current paper describes the process by
      which the MAMA team brainstormed proposed services and administered their survey.
      Survey results and the consequent changes to the MAMA system are discussed.
      Finally, recommendations are made for MAMA system use and a description is
      offered of the impact such systems might have on the future of college campus
      healthcare services.

PMID- 19167272
TI  - Druggable targets for sudden cardiac death prevention: lessons from the past and
      strategies for the future.
AB  - Sudden cardiac death (SCD) is most commonly caused by ventricular fibrillation
      (VF). The single largest cohort of victims is the population with little or no
      prior overt heart disease. Effective prevention will require long-term
      prophylaxis by drugs in large numbers of people identified by risk factors. This
      means that safe as well as effective drugs are required. Drugs with overt effects
      on cardiac electrophysiology have failed in the clinic owing to poor
      effectiveness and/or adverse effects. This article examines possible new drug
      targets. We have focused on acute myocardial ischaemia as it is the most
      strikingly proarrhythmic pathology, and the most common cause of coronary artery
      disease-related VF and SCD according to inferences from epidemiology, drug trials
      and decades of animal research. To set the scene we have briefly explored drugs
      that have failed in the clinic in order to identify possible targets that have
      been overlooked or underexploited. We conclude that the best strategy is
      identification of pathology-specific targets that render drugs active only where
      and when their action is required.

PMID- 19167273
TI  - The use of botulinum toxin in the pelvic floor for women with chronic pelvic pain
      a new answer to old problems?
AB  - Chronic pelvic pain occurs in about 15% of women and has a variety of causes
      requiring accurate diagnosis and appropriate treatment if pain reduction is to be
      effected. Superficial conditions such as provoked vestibulodynia and deeper
      pelvic issues such as pelvic floor myalgia were traditionally difficult to
      diagnose and adequately treat. For provoked vestibulodynia, there are limited
      data, in the form of case reports and small series, to indicate that botulinum
      toxin (BoNT) injections may provide short-term (3-6 months) benefit. Retreatment
      is reported to be successful and side effects are few. Class-I studies are
      essential to adequately assess this form of treatment. For pelvic floor myalgia,
      1 class-I study and 3 class-II to -III studies indicate efficacy of BoNT. In the
      only double-blind, randomized, controlled study, significant reduction in pelvic
      floor pressures with significant pain reduction for some types of pelvic pain are
      reported compared with baseline. No differences in pain occurred compared with
      the control group who had physical therapy as an intervention. Physical therapy
      should be used as a noninvasive first-line treatment, with BoNT injections
      reserved for those who are refractory to treatment. Pelvic floor disorders should
      be considered as a cause for chronic pelvic pain in women and an attempt made to
      diagnose and treat such problems as a routine practice. The use of BoNT as a
      therapeutic option for pelvic floor muscle spasm and pain is still in its
      infancy. Initial reports suggest that there may be a significant role for women
      with chronic pain that is refractory to currently available medical and surgical
      treatments, however, there are very few high-quality studies and research is
      essential before this novel treatment can be accepted into widespread use for
      pelvic pain attributable to the pelvic floor.

PMID- 19167274
TI  - Determination of asiatic acid in beagle dog plasma after oral administration of
      Centella asiatica extract by precolumn derivatization RP-HPLC.
AB  - A novel precolumn derivatization reversed-phase high-performance liquid
      chromatography (RP-HPLC) method with UV-vis detection for the quantitative
      determination of total concentration of asiatic acid (AA) in beagle dog plasma is
      described. AA was extracted with n-hexane-dichloromethane-2-propanol (20:10:1,
      v/v/v) from plasma, which had been hydrolyzed by acid and derivatized with p
      Toluidine. Chromatographic separation was achieved on a C(18) column using
      gradient elution in a water-methanol system. Detection was set at UV wavelength
      of 248nm. A calibration curve ranging from 0.01 to 1.5microg/mL was shown to be
      linear, and the lower limit of quantification (LLOQ) was 0.01microg/mL. The intra
      and inter-day precisions which were determined by three different concentrations
      (0.05, 0.2 and 0.8microg/mL) ranged from 4.4% to 13.1% and 4.6% to 14.2%,
      respectively. Mean extraction recoveries were no less than 65% for AA and ursolic
      acid (IS). Plasma samples containing asiatic acid were stable for 30 days at -20
      degrees C. The method was successfully applied to a pharmacokinetic study in
      beagle dogs after oral administration of Centella asiatica extract, and the main
      pharmacokinetic parameters obtained were: T(1/2), 4.29h; T(max), 2.70h; C(max),
      0.74microg/mL; AUC(0-t) and AUC(0-infinity), 3.74 and 3.82microgh/mL,
      respectively.

PMID- 19167275
TI  - Liquid chromatography-tandem mass spectrometry method for the simultaneous
      quantitative determination of the organophosphorus pesticides dimethoate,
      fenthion, diazinon and chlorpyrifos in human blood.
AB  - Simultaneous determination of the organophosphorus pesticides dimethoate,
      fenthion, diazinon and chlorpyrifos in human blood by HPLC-tandem mass
      spectrometry was developed and validated. The pesticides were extracted by a
      simple one-step protein precipitation procedure. Chromatography was performed on
      a Luna C(18) (30mmx2.0mm, 3microm) column, using a step-gradient at a flow rate
      of 0.4ml/min. The assay was linear from 0.5 to 100ng/ml (r(2)>0.992, n=24) for
      all pesticides. The inter- and intra-day accuracy and precision for the method
      was 96.6-106.1% and <10%, respectively. The lower limit of quantification was
      0.5ng/ml. In conclusion, the method described displays analytical performance
      characteristics that are suitable for the quantification of these pesticides in
      cases of acute poisoning.

PMID- 19167276
TI  - Chromatographic separation of (E)- and (Z)-isomers of entacapone and their
      simultaneous quantitation in human plasma by LC-ESI-MS/MS.
AB  - A selective, sensitive and high throughput liquid chromatography-tandem mass
      spectrometry (LC-ESI-MS/MS) method has been developed and validated for the
      chromatographic separation and quantitation of (E)-entacapone and (Z)-entacapone
      in human plasma. Sample clean-up involved liquid-liquid extraction (LLE) of both
      the isomers and carbamazepine used as internal standard from 500microL of human
      plasma. Both the analytes were chromatographically separated with a resolution
      factor of 3.0 on a Gemini C18 (50mmx4.6mm, 5microm particle size) analytical
      column using 1% formic acid and methanol (50:50, v/v) as the mobile phase. The
      selectivity factor (alpha) of the column for the separation was 2.0, based on the
      capacity factors of 2.6 and 1.3 for (E)- and (Z)-isomers respectively. The parent
      ->product ion transitions for both the isomers (m/z 306.1-->233.0) and IS (m/z
      237.3-->194.2) were monitored on a triple quadrupole mass spectrometer, operating
      in the multiple reaction monitoring (MRM) and positive ion mode. The method was
      validated over the concentration range of 24.3-6076ng/mL and 23.8-5960ng/mL for
      (E)-entacapone and (Z)-entacapone respectively. Matrix effect was assessed by
      post-column analyte infusion experiment and the process/extraction efficiency
      found was 94.3% and 89.3% for (E)- and (Z)-isomers respectively. The method was
      successfully applied to a pivotal bioequivalence study in 36 healthy human
      subjects after oral administration of 200mg (E)-entacapone tablet formulation
      under fasting conditions.

PMID- 19167278
TI  - WITHDRAWN: The weakest link?
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published, doi: 10.1016/j.ijsu.2007.11.001. The
      duplicate article has therefore been withdrawn.

PMID- 19167277
TI  - Production of heparin-containing hydrogels for modulating cell responses.
AB  - Successful tissue regeneration requires that biomaterials have optimal
      bioactivity and mechanical properties. Heparin-containing hydrogels that can be
      crosslinked in situ were designed to contain tunable amounts of biological
      components (e.g. heparin, arginine-glycine-aspartate (RGD)) as well as to exhibit
      controlled mechanical properties (e.g. shear modulus). These gel parameters can
      also be tuned to provide controlled delivery of proteins, such as growth factors,
      for regulating cellular behavior. Maleimide-functionalized low-molecular-weight
      heparin (LWMH) was conjugated to a poly(ethylene glycol) (PEG) hydrogel. The
      elastic shear modulus, as assessed via oscillatory rheology experiments, could be
      tuned by the concentration of polymer in the hydrogel, and by the end group
      functionality of PEG. Hydrogels of two different moduli (2.8 and 0.4kPa) were
      used to study differences in the response of human aortic adventitial fibroblasts
      (AoAF) in two-dimensional cell culture experiments. These experiments indicated
      that the AoAFs show improved adhesion to materials with the higher modulus.
      Evaluation of cell responses to hydrogels with RGD linked to the hydrogels via
      conjugation to PEG or to LMWH indicated improved cellular responses to these
      materials when the bioactive ligands were chemically attached through linkage to
      the PEG rather than to the LMWH. These results highlight important design
      considerations in the tailoring of these materials for cardiovascular tissue
      engineering applications.

PMID- 19167279
TI  - Silicone moulding for pressure sore debridement.
AB  - The radicality of wound debridement is an important feature of the surgical
      treatment of pressure sores. Several methods such as injection of methylene blue
      or hydrogen peroxide have been proposed to facilitate and optimise the surgical
      debridement technique, but none of them proved to be sufficient. We present an
      innovative modification of the pseudo-tumour technique consisting in the
      injection of fluid silicone. Vulcanization of the silicone leads to pressure-sore
      moulding, permitting a more radical and sterile excision. In a series of 10
      paraplegic patients presenting with ischial pressure sores, silicone moulding was
      used to facilitate debridement. Radical en bloc debridement was achieved in all
      patients. After a minimal follow-up of 2 years, no complications and recurrences
      occurred. A three-dimensional (3D) analysis of the silicone prints objectified
      the pyramidal shape of ischial pressure sores. Our study showed that complete
      resection without capsular lesion can be easily achieved. Further, it allows the
      surgeon to analyse the shape and size of the resected defect, which might be
      helpful to select the appropriate defect coverage technique.

PMID- 19167280
TI  - Determination of pore-lining residues in the hepatitis C virus p7 protein.
AB  - The p7 protein from hepatitis C virus is critical for the assembly and secretion
      of infectious virus, making it an attractive drug target. It is thought to be a
      viroporin with a demonstrated ion channel activity when reconstituted into planar
      lipid bilayers. Electron microscopy experiments suggest that p7 oligomers coexist
      as hexamers and heptamers. Proposed models of p7 oligomers assume the N-terminal
      helix to be the pore lining helix. Here, we demonstrate, via electrophysiology,
      that Cu(2+) has an inhibitory effect on the p7 ion channel and that the amino
      acid responsible for this inhibition is one histidine in each monomer. This
      information coupled with the p7 sequence data suggests that the N-terminal helix
      of p7 does indeed form the transmembrane pore and that this histidine is pore
      lining. The information will aid in the construction of oligomeric pore-models
      and the interpretation of electron microscopy data.

PMID- 19167281
TI  - Live cell linear dichroism imaging reveals extensive membrane ruffling within the
      docking structure of natural killer cell immune synapses.
AB  - We have applied fluorescence imaging of two-photon linear dichroism to measure
      the subresolution organization of the cell membrane during formation of the
      activating (cytolytic) natural killer (NK) cell immune synapse (IS). This
      approach revealed that the NK cell plasma membrane is convoluted into ruffles at
      the periphery, but not in the center of a mature cytolytic NK cell IS. Time-lapse
      imaging showed that the membrane ruffles formed at the initial point of contact
      between NK cells and target cells and then spread radialy across the
      intercellular contact as the size of the IS increased, becoming absent from the
      center of the mature synapse. Understanding the role of such extensive membrane
      ruffling in the assembly of cytolytic synapses is an intriguing new goal.

PMID- 19167282
TI  - Theoretical limits on errors and acquisition rates in localizing switchable
      fluorophores.
AB  - A variety of recent imaging techniques are able to beat the diffraction limit in
      fluorescence microcopy by activating and localizing subsets of the fluorescent
      molecules in the specimen, and repeating this process until all of the molecules
      have been imaged. In these techniques there is a tradeoff between speed
      (activating more molecules per imaging cycle) and error rates (activating more
      molecules risks producing overlapping images that hide information on molecular
      positions), and so intelligent image processing approaches are needed to identify
      and reject overlapping images. We introduce here a formalism for defining error
      rates, derive a general relationship between error rates, image acquisition
      rates, and the performance characteristics of the image processing algorithms,
      and show that there is a minimum acquisition time irrespective of algorithm
      performance. We also consider algorithms that can infer molecular positions from
      images of overlapping blurs, and derive the dependence of the minimum acquisition
      time on algorithm performance.

PMID- 19167283
TI  - Charge movement of a voltage-sensitive fluorescent protein.
AB  - The N-terminus of Ciona intestinalis (Ci-VSP) is a voltage-sensing domain (VSD)
      controlling the activity of a phosphatase domain on the C terminus. By replacing
      the phosphatase domain with a tandem of fluorescent proteins, CFP and YFP, a
      family of fluorescence resonance energy transfer-based, genetically encoded
      voltage-sensing fluorescent protein (VSFP) was created. VSFP2.3, one of the
      latest versions of this family, showed large changes in YFP emission upon changes
      in membrane potential with CFP excitation when expressed in Xenopus laevis
      oocytes. The time course of the fluorescence has two components: the fast
      component correlates with the time course of sensing current produced by the
      charge movement, while the slow component is at least one order-of-magnitude
      slower than the sensing current. This suggests that the tandem of fluorescent
      proteins reports a secondary conformational transition of the VSD which resembles
      the relaxation of the VSD of Ci-VSP described in detail for the Ci-VSP. This
      observation indicates that the relaxation of the VSD of VSFP2.3 is a global
      conformational change that encompasses the entire S4 segment.

PMID- 19167284
TI  - Light-induced dark states of organic fluochromes enable 30 nm resolution imaging
      in standard media.
AB  - We show that high quantum efficiency fluorophores can exhibit reversible
      photobleaching. This observation provides the basis for an imaging technique we
      call reversible photobleaching microscopy. We demonstrate applicability of this
      technique using antibody labeled biological samples in standard aqueous (or
      glycerol based) media to produce far-field images at approximately 30 nm
      resolution. Our novel method relies on intense illumination to reversibly induce
      a very long-lived (>10 s) dark state from which single fluorochromes slowly
      return stochastically. As in other localization microscopy methods, reversible
      photobleaching microscopy localizes single fluorochromes, but has the advantage
      that specialized photoactivatible and photoswitchable molecules or special
      immersion/embedding media are not required.

PMID- 19167285
TI  - Nonlocal helix formation is key to understanding S-adenosylmethionine-1
      riboswitch function.
AB  - Riboswitches are noncoding RNAs that regulate gene expression in response to
      changing concentrations of specific metabolites. Switching activity is affected
      by the interplay between the aptamer domain and expression platform of the
      riboswitch. The aptamer domain binds the metabolite, locking the riboswitch in a
      ligand-bound conformation. In absence of the metabolite, the expression platform
      forms an alternative secondary structure by sequestering the 3' end of a nonlocal
      helix called P1. We use all-atom structure-based simulations to characterize the
      folding, unfolding, and metabolite binding of the aptamer domain of the S
      adenosylmethionine-1 (SAM-1) riboswitch. Our results suggest that folding of the
      nonlocal helix (P1) is rate-limiting in aptamer domain formation. Interestingly,
      SAM assists folding of the P1 helix by reducing the associated free energy
      barrier. Because the 3' end of the P1 helix is sequestered by an alternative
      helix in the absence of metabolites, this observed ligand-control of P1 formation
      provides a mechanistic explanation of expression platform regulation.

PMID- 19167286
TI  - Atomic force microscopy of biological membranes.
AB  - Atomic force microscopy (AFM) is an ideal method to study the surface topography
      of biological membranes. It allows membranes that are adsorbed to flat solid
      supports to be raster-scanned in physiological solutions with an atomically sharp
      tip. Therefore, AFM is capable of observing biological molecular machines at
      work. In addition, the tip can be tethered to the end of a single membrane
      protein, and forces acting on the tip upon its retraction indicate barriers that
      occur during the process of protein unfolding. Here we discuss the fundamental
      limitations of AFM determined by the properties of cantilevers, present aspects
      of sample preparation, and review results achieved on reconstituted and native
      biological membranes.

PMID- 19167287
TI  - The scaling of blood flow resistance: from a single vessel to the entire distal
      tree.
AB  - Although the flow resistance of a single vessel segment is easy to compute, the
      equivalent resistance of a network of vessel segments or the entire vasculature
      of an organ is difficult to determine in an analytic form. Here, we propose what
      we believe is a novel resistance scaling law for a vascular tree (i.e., the
      resistance of a vessel segment scales with the equivalent resistance of the
      corresponding distal tree). The formulation can be written as (R(s)/R(c))
      proportional, variant(L(s)/L(c)) (where R(s) and L(s) are the resistance and
      length of a vessel segment, respectively, and R(c) and L(c) are the equivalent
      resistance and total length of the corresponding distal tree, respectively),
      which was validated for the coronary vascular systems of the heart. The scaling
      law was also shown to apply to the vascular systems of the lung, mesentery,
      muscle, eye, and so on. The novel resistance scaling law, coupled with the 3/4
      power scaling law for metabolic rates, can predict several structure-function
      relations of vascular trees, albeit with a different exponent. In particular, the
      self-similar nature of the scaling law may serve as a diagnostic tool with the
      help of noninvasive imaging modalities.

PMID- 19167288
TI  - A scaling law of vascular volume.
AB  - Vascular volume is of fundamental significance to the function of the
      cardiovascular system. An accurate prediction of blood volume in patients is
      physiologically and clinically significant. This study proposes what we believe
      is a novel volume scaling relation of the form: V(c)=K(v)D(s)(2/3)L(c), where
      V(c) and L(c) are cumulative vessel volume and length, respectively, in the tree,
      and D(s) is the diameter of the vessel segment. The scaling relation is validated
      in vascular trees of various organs including the heart, lung, mesentery, muscle,
      and eye of different species. Based on the minimum energy hypothesis and volume
      scaling relation, four structure-function scaling relations are predicted,
      including the diameter-length, volume-length, flow-diameter, and volume-diameter
      relations, with exponent values of 3/7, 1(2/7), 2(1/3), and 3, respectively.
      These four relations are validated in the various vascular trees, which further
      confirm the volume scaling relation. This scaling relation may serve as a control
      reference to estimate the blood volume in various organs and species. The
      deviation from the scaling relation may indicate hypovolemia or hypervolemia and
      aid diagnosis.

PMID- 19167289
TI  - Thermal stability of apolipoprotein A-I in high-density lipoproteins by molecular
      dynamics.
AB  - Apolipoprotein (apo) A-I is an unusually flexible protein whose lipid-associated
      structure is poorly understood. Thermal denaturation, which is used to measure
      the global helix stability of high-density lipoprotein (HDL)-associated apoA-I,
      provides no information about local helix stability. Here we report the use of
      temperature jump molecular dynamics (MD) simulations to scan the per-residue
      helix stability of apoA-I in phospholipid-rich HDL. When three 20 ns MD
      simulations were performed at 500 K on each of two particles created by MD
      simulations at 310 K, bilayers remained intact but expanded by 40%, and total
      apoA-I helicity decreased from 95% to 72%. Of significance, the conformations of
      the overlapping N- and C-terminal domains of apoA-I in the particles were
      unusually mobile, exposing hydrocarbon regions of the phospholipid to solvent; a
      lack of buried interhelical salt bridges in the terminal domains correlated with
      increased mobility. Nondenaturing gradient gels show that 40% expansion of the
      phospholipid surface of 100:2 particles by addition of
      palmitoyloleoylphosphatidylcholine exceeds the threshold of particle stability.
      As a unifying hypothesis, we propose that the terminal domains of apoA-I are
      phospholipid concentration-sensitive molecular triggers for fusion/remodeling of
      HDL particles. Since HDL remodeling is necessary for cholesterol transport, our
      model for remodeling has substantial biomedical implications.

PMID- 19167290
TI  - Translational repression contributes greater noise to gene expression than
      transcriptional repression.
AB  - Stochastic effects in gene expression may result in different physiological
      states of individual cells, with consequences for pathogen survival and
      artificial gene network design. We studied the contributions of a regulatory
      factor to gene expression noise in four basic mechanisms of negative gene
      expression control: 1), transcriptional regulation by a protein repressor, 2),
      translational repression by a protein; 3), transcriptional repression by RNA; and
      4), RNA interference with the translation. We investigated a general model of a
      two-gene network, using the chemical master equation and a moment generating
      function approach. We compared the expression noise of genes with the same
      effective transcription and translation initiation rates resulting from the
      action of different repressors, whereas previous studies compared the noise of
      genes with the same mean expression level but different initiation rates. Our
      results show that translational repression results in a higher noise than
      repression on the promoter level, and that this relationship does not depend on
      quantitative parameter values. We also show that regulation of protein
      degradation contributes more noise than regulated degradation of mRNA. These are
      unexpected results, because previous investigations suggested that translational
      regulation is more accurate. The relative magnitude of the noise introduced by
      protein and RNA repressors depends on the protein and mRNA degradation rates, and
      we derived expressions for the threshold below which the noise introduced by a
      protein repressor is higher than the noise introduced by an RNA repressor.

PMID- 19167291
TI  - Molecular dynamics simulations of a DMPC bilayer using nonadditive interaction
      models.
AB  - We present a polarizable force field based on the charge-equilibration formalism
      for molecular dynamics simulations of phospholipid bilayers. We discuss
      refinement of headgroup dihedral potential parameters to reproduce ab initio
      conformational energies of dimethylphosphate calculated at the MP2/cc-pVTZ level
      of theory. We also address the refinement of electrostatic and Lennard-Jones (van
      der Waals) parameters to reproduce ab initio polarizabilities and water
      interaction energies of dimethylphosphate and tetramethylammonium. We present
      results of molecular dynamics simulations of a solvated
      dimyristoylphosphatidylcholine bilayer using this polarizable force field as well
      as the nonpolarizable, fixed-charge CHARMM27 and CHARMM27r force fields for
      comparison. Calculated atomic and electron-density profiles, deuterium order
      parameters, and headgroup orientations are found to be consistent with previous
      simulations and with experiment. Polarizable interaction models for solvent and
      lipid exhibit greater water penetration into the lipid interior; this is due to
      the variation of water molecular dipole moment from a bulk value of 2.6 Debye to
      a value of 1.9 Debye in the membrane interior. The reduction in the electrostatic
      component of the desolvation free-energy penalty allows for greater water
      density. The surface dipole potential predicted by the polarizable model is 0.95
      V compared to the value of 0.8 V based on nonpolarizable force-field
      calculations. Effects of inclusion of explicit polarization are discussed in
      relation to water dipole moment and varying charge distributions. Dielectric
      permittivity profiles for polarizable and nonpolarizable interactions exhibit
      subtle differences arising from the nature of the individual component
      parameterizations; for the polarizable force field, we obtain a bulk dielectric
      permittivity of 79, whereas the nonpolarizable force field plateaus at 97 (the
      value for pure TIP3P water). In the membrane interior, both models predict unit
      permittivities, with the polarizable models contributing from one to two more
      units due to the optical dielectric (high-frequency dipole fluctuations). This
      contribution is a step toward the continuing development of a CHARMM (Chemistry
      at Harvard Molecular Mechanics) polarizable force field for simulations of
      biomacromolecular systems.

PMID- 19167292
TI  - Photochemical reaction dynamics of the primary event of vision studied by means
      of a hybrid molecular simulation.
AB  - The photoisomerization reaction dynamics of a retinal chromophore in the visual
      receptor rhodopsin was investigated by means of hybrid quantum
      mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations. The
      photoisomerization reaction of retinal constitutes the primary step of vision and
      is known as one of the fastest reactions in nature. To elucidate the molecular
      mechanism of the high efficiency of the reaction, we carried out hybrid ab initio
      QM/MM MD simulations of the complete reaction process from the vertically excited
      state to the photoproduct via electronic transition in the entire chromophore
      protein complex. An ensemble of reaction trajectories reveal that the excited
      state dynamics is dynamically homogeneous and synchronous even in the presence of
      thermal fluctuation of the protein, giving rise to the very fast formation of the
      photoproduct. The synchronous nature of the reaction dynamics in rhodopsin is
      found to originate from weak perturbation of the protein surroundings and from
      dynamic regulation of volume-conserving motions of the chromophore. The
      simulations also provide a detailed view of time-dependent modulations of
      hydrogen-out-of-plane vibrations during the reaction process, and identify
      molecular motions underlying the experimentally observed dynamic spectral
      modulations.

PMID- 19167293
TI  - Oscillatory NAD(P)H waves and calcium oscillations in neutrophils? A modeling
      study of feasibility.
AB  - The group of Howard Petty has claimed exotic metabolic wave phenomena together
      with mutually phase-coupled NAD(P)H- and calcium-oscillations in human
      neutrophils. At least parts of these phenomena are highly doubtful due to
      extensive failure of reproducibility by several other groups and hints that
      unreliable data from the Petty lab are involved in publications concerning
      circular calcium waves. The aim of our theoretical spatiotemporal modeling
      approach is to propose a possible and plausible biochemical mechanism which
      would, in principle, be able to explain metabolic oscillations and wave phenomena
      in neutrophils. Our modeling suggests the possibility of a calcium-controlled
      glucose influx as a driving force of metabolic oscillations and a potential role
      of polarized cell geometry and differential enzyme distribution for various
      NAD(P)H wave phenomena. The modeling results are supposed to stimulate further
      controversial discussions of such phenomena and potential mechanisms and
      experimental efforts to finally clarify the existence and biochemical basis of
      any kind of temporal and spatiotemporal patterns of calcium signals and metabolic
      dynamics in human neutrophils. Independent of Petty's observations, they present
      a general feasibility study of such phenomena in cells.

PMID- 19167294
TI  - Changing the mechanical unfolding pathway of FnIII10 by tuning the pulling
      strength.
AB  - We investigate the mechanical unfolding of the tenth type III domain from
      fibronectin (FnIII(10)) both at constant force and at constant pulling velocity,
      by all-atom Monte Carlo simulations. We observe both apparent two-state unfolding
      and several unfolding pathways involving one of three major, mutually exclusive
      intermediate states. All three major intermediates lack two of seven native beta
      strands, and share a quite similar extension. The unfolding behavior is found to
      depend strongly on the pulling conditions. In particular, we observe large
      variations in the relative frequencies of occurrence for the intermediates. At
      low constant force or low constant velocity, all three major intermediates occur
      with a significant frequency. At high constant force or high constant velocity,
      one of them, with the N- and C-terminal beta-strands detached, dominates over the
      other two. Using the extended Jarzynski equality, we also estimate the
      equilibrium free-energy landscape, calculated as a function of chain extension.
      The application of a constant pulling force leads to a free-energy profile with
      three major local minima. Two of these correspond to the native and fully
      unfolded states, respectively, whereas the third one can be associated with the
      major unfolding intermediates.

PMID- 19167295
TI  - Replica exchange simulations of the thermodynamics of Abeta fibril growth.
AB  - Replica exchange molecular dynamics and an all-atom implicit solvent model are
      used to probe the thermodynamics of deposition of Alzheimer's Abeta monomers on
      preformed amyloid fibrils. Consistent with the experiments, two deposition stages
      have been identified. The docking stage occurs over a wide temperature range,
      starting with the formation of the first peptide-fibril interactions at 500 K.
      Docking is completed when a peptide fully adsorbs on the fibril edge at the
      temperature of 380 K. The docking transition appears to be continuous, and occurs
      without free energy barriers or intermediates. During docking, incoming Abeta
      monomer adopts a disordered structure on the fibril edge. The locking stage
      occurs at the temperature of approximately 360 K and is characterized by the
      rugged free energy landscape. Locking takes place when incoming Abeta peptide
      forms a parallel beta-sheet structure on the fibril edge. Because the beta-sheets
      formed by locked Abeta peptides are typically off-registry, the structure of the
      locked phase differs from the structure of the fibril interior. The study also
      reports that binding affinities of two distinct fibril edges with respect to
      incoming Abeta peptides are different. The peptides bound to the concave edge
      have significantly lower free energy compared to those bound on the convex edge.
      Comparison with the available experimental data is discussed.

PMID- 19167296
TI  - Polar chemoreceptor clustering by coupled trimers of dimers.
AB  - Receptors of bacterial chemotaxis form clusters at the cell poles, where clusters
      act as "antennas" to amplify small changes in ligand concentration. It is worthy
      of note that chemoreceptors cluster at multiple length scales. At the smallest
      scale, receptors form dimers, which assemble into stable timers of dimers. At a
      large scale, trimers form large polar clusters composed of thousands of
      receptors. Although much is known about the signaling properties emerging from
      receptor clusters, it is unknown how receptors localize at the cell poles and
      what the determining factors are for cluster size. Here, we present a model of
      polar receptor clustering based on coupled trimers of dimers, where cluster size
      is determined as a minimum of the cluster-membrane free energy. This energy has
      contributions from the cluster-membrane elastic energy, penalizing large clusters
      due to their high intrinsic curvature, and receptor-receptor coupling that favors
      large clusters. We find that the reduced cluster-membrane curvature mismatch at
      the curved cell poles leads to large and robust polar clusters, in line with
      experimental observation, whereas lateral clusters are efficiently suppressed.

PMID- 19167297
TI  - Application of elastic network models to proteins in the crystalline state.
AB  - Normal mode analysis using elastic network models has grown popular for probing
      the low-frequency collective dynamics of proteins and other biomolecular
      assemblies. In most previous studies, these models were validated by comparing
      calculated atomic fluctuations for isolated proteins with experimental
      temperature factors determined in the crystalline state, although there were also
      hints that including crystal contacts in the calculations has an impact on the
      comparison. In this study, a set of 83 ultra-high resolution crystal structures
      with experimentally determined anisotropic displacement parameters is used to
      evaluate several C(alpha)-based elastic network models that either ignore or
      treat the crystal environment in different ways; the latter include using
      periodic boundary conditions defined with respect to the asymmetric unit or the
      primitive unit cell as well as using the Born-von Karman boundary condition that
      accounts for lattice vibrations. For all elastic network models, treating the
      crystal environment leads to better agreement with experimental anisotropic
      displacement parameters with the Born-von Karman boundary condition giving the
      best agreement. Atomic correlations over the entire protein are clearly affected
      by the presence of the crystal contacts and fairly sensitive to the way that the
      crystal environment is treated. These observations highlight the importance of
      properly treating the protein system in an environment consistent with experiment
      when either evaluating approximate protein models or using approximate dynamic
      models in structural refinement application types. Finally, investigation of the
      scaling behaviors of the cumulative density of states and the heat capacity
      indicates that there are still gaps between simplified elastic models and all
      atom models for proteins.

PMID- 19167298
TI  - Instantaneous normal modes and the protein glass transition.
AB  - In the instantaneous normal mode method, normal mode analysis is performed at
      instantaneous configurations of a condensed-phase system, leading to modes with
      negative eigenvalues. These negative modes provide a means of characterizing
      local anharmonicities of the potential energy surface. Here, we apply
      instantaneous normal mode to analyze temperature-dependent diffusive dynamics in
      molecular dynamics simulations of a small protein (a scorpion toxin). Those
      characteristics of the negative modes are determined that correlate with the
      dynamical (or glass) transition behavior of the protein, as manifested as an
      increase in the gradient with T of the average atomic mean-square displacement at
      approximately 220 K. The number of negative eigenvalues shows no transition with
      temperature. Further, although filtering the negative modes to retain only those
      with eigenvectors corresponding to double-well potentials does reveal a
      transition in the hydration water, again, no transition in the protein is seen.
      However, additional filtering of the protein double-well modes, so as to retain
      only those that, on energy minimization, escape to different regions of
      configurational space, finally leads to clear protein dynamical transition
      behavior. Partial minimization of instantaneous configurations is also found to
      remove nondiffusive imaginary modes. In summary, examination of the form of
      negative instantaneous normal modes is shown to furnish a physical picture of
      local diffusive dynamics accompanying the protein glass transition.

PMID- 19167299
TI  - Model development for the viral Kcv potassium channel.
AB  - A computational model for the open state of the short viral Kcv potassium channel
      was created and tested based on homology modeling and extensive molecular
      dynamics simulation in a membrane environment. Particular attention was paid to
      the structure of the highly flexible N-terminal region and to the protonation
      state of membrane-exposed lysine residues. Data from various experimental
      sources, NMR spectroscopy, and electrophysiology, as well as results from three
      dimensional reference interaction site model integral equation theory were taken
      into account to select the most reasonable model among possible variants. The
      final model exhibits spontaneous ion transitions across the complete pore, with
      and without application of an external field. The nonequilibrium transport events
      could be induced reproducibly without abnormally large driving potential and
      without the need to place ions artificially at certain key positions along the
      transition path. The transport mechanism through the filter region corresponds to
      the classic view of single-file motion, which in our case is coupled to frequent
      exchange of ions between the innermost filter position and the cavity.

PMID- 19167300
TI  - Distinct structural changes in the GABAA receptor elicited by pentobarbital and
      GABA.
AB  - The barbiturate pentobarbital binds to gamma-aminobutyric acid type A (GABA(A))
      receptors, and this interaction plays an important role in the anesthetic action
      of this drug. Depending on its concentration, pentobarbital can potentiate
      (approximately 10-100 microM), activate (approximately 100-800 microM), or block
      (approximately 1-10 mM) the channel, but the mechanisms underlying these three
      distinct actions are poorly understood. To investigate the drug-induced
      structural rearrangements in the GABA(A) receptor, we labeled cysteine mutant
      receptors expressed in Xenopus oocytes with the sulfhydryl-reactive,
      environmentally sensitive fluorescent probe tetramethylrhodamine-6-maleimide
      (TMRM). We then used combined voltage clamp and fluorometry to monitor
      pentobarbital-induced channel activity and local protein movements simultaneously
      in real time. High concentrations of pentobarbital induced a decrease in TMRM
      fluorescence (F(TMRM)) of labels tethered to two residues in the extracellular
      domain (alpha(1)L127C and beta(2)L125C) that have been shown previously to
      produce an increase in F(TMRM) in response to GABA. Label at beta(2)K274C in the
      extracellular end of the M2 transmembrane helix reported a small but significant
      F(TMRM) increase during application of low modulating pentobarbital
      concentrations, and it showed a much greater F(TMRM) increase at higher
      concentrations. In contrast, GABA decreased F(TMRM) at this site. These results
      indicate that GABA and pentobarbital induce different structural rearrangements
      in the receptor, and thus activate the receptor by different mechanisms. Labels
      at alpha(1)L127C and beta(2)K274C change their fluorescence by substantial
      amounts during channel blockade by pentobarbital. In contrast, picrotoxin
      blockade produces no change in F(TMRM) at these sites, and the pattern of F(TMRM)
      signals elicited by the antagonist SR95531 differs from that produced by other
      antagonists. Thus, with either channel block by antagonists or activation by
      agonists, the structural changes in the GABA(A) receptor protein differ during
      transitions that are functionally equivalent.

PMID- 19167301
TI  - Amphipath-induced nanoscale changes in outer hair cell plasma membrane curvature.
AB  - Outer hair cell (OHC) electromotility enables frequency selectivity and
      sensitivity in mammalian audition. Electromotility is generated by the
      transmembrane protein prestin and is sensitive to amphipathic compounds including
      salicylate, chlorpromazine (CPZ), and trinitrophenol (TNP). Although these
      compounds induce observable membrane curvature changes in erythrocytes, their
      effects on OHC membrane curvature are unknown. In this work, fluorescence
      polarization microscopy was applied to investigate the effects of salicylate,
      CPZ, and TNP on di-8-ANEPPS orientation in the OHC plasma membrane. Our results
      demonstrate the ability of fluorescence polarization microscopy to measure
      amphipath-induced changes in di-8-ANEPPS orientation, consistent with nanoscale
      changes in membrane curvature between regularly spaced proteins connecting the
      OHC plasma membrane and cytoskeleton. Simultaneous application of oppositely
      charged amphipaths generally results in no net membrane bending, consistent with
      predictions of the bilayer couple hypothesis; however, the application of
      salicylate (10 mM), which inhibits electromotility, is not reversed by the
      addition of CPZ. This result supports other findings that suggest salicylate
      primarily influences electromotiliy and OHC nonlinear capacitance via a direct
      interaction with prestin. In contrast, we find that CPZ and TNP influence the
      voltage sensitivity of prestin via membrane bending, demonstrating the
      mechanosensitivity of this unique membrane motor protein.

PMID- 19167302
TI  - Phase equilibria in DOPC/DPPC-d62/cholesterol mixtures.
AB  - There is broad interest in the question of fluid-fluid phase coexistence in
      membranes, in particular, whether evidence for liquid-disordered (l(d))-liquid
      ordered (l(o)) two-phase regions or membrane "rafts" can be found in natural
      membranes. In model membrane systems, such phase behavior is observed, and we
      have used deuterium nuclear magnetic resonance spectroscopy to map the phase
      boundaries of ternary mixtures containing 1,2-dioleoyl-sn-glycero-3
      phosphocholine (DOPC), chain-perdeuterated 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC-d(62)), and cholesterol. For both this ternary model system
      and the binary DPPC-d(62)/cholesterol system, we present clear evidence for l(d)
      l(o) two-phase coexistence. We have selected sample compositions to focus on this
      region of fluid-fluid phase coexistence and to determine its temperature and
      composition ranges. The deuterium nuclear magnetic resonance spectra for
      compositions near the l(d)-l(o) phase boundary at high cholesterol concentrations
      show evidence of exchange broadening or critical fluctuations in composition,
      similar to that reported by Vist and Davis. There appears to be a line of
      critical compositions ranging from 48 degrees C for a DOPC/DPPC-d(62)/cholesterol
      composition of 0:75:25, to approximately -8 degrees C for the composition
      57:14:29. At temperatures below this two-phase region, there is a region of three
      phase coexistence (l(d)-l(o)-gel). These results are collected and presented in
      terms of a partial ternary phase diagram that is consistent with previously
      reported results of Vist and Davis.

PMID- 19167303
TI  - Clustering of alpha-synuclein on supported lipid bilayers: role of anionic lipid,
      protein, and divalent ion concentration.
AB  - Alpha-synuclein is the major component of Lewy body inclusions found in the
      brains of patients with Parkinson's disease. Several studies indicate that alpha
      synuclein binds to negatively charged phospholipid bilayers. We examined the
      binding of alpha-synuclein to membranes containing different amounts of
      negatively charged lipids using supported lipid bilayers, epifluorescence
      microscopy, fluorescence recovery after photobleaching, and bulk fluorescence
      techniques. The membranes contained phosphatidylcholine and phosphatidylglycerol.
      In the absence of protein, these lipids mix uniformly. Our results show that the
      propensity of alpha-synuclein to cluster on the membrane increases as the
      concentration of anionic lipid and/or protein increases. Regions on the lipid
      bilayer where alpha-synuclein is clustered are enriched in phosphatidylglycerol.
      We also observe divalent metal ions stimulate protein cluster formation,
      primarily by promoting lipid demixing. The importance of protein structure, lipid
      demixing, and divalent ions, as well as the physiological implications, will be
      discussed. Because membrane-bound alpha-synuclein assemblies may play a role in
      neurotoxicity, it is of interest to determine how membranes can be used to tune
      the propensity of alpha-synuclein to aggregate.

PMID- 19167304
TI  - Effect of membrane composition on antimicrobial peptides aurein 2.2 and 2.3 from
      Australian southern bell frogs.
AB  - The effects of hydrophobic thickness and the molar phosphatidylglycerol (PG)
      content of lipid bilayers on the structure and membrane interaction of three
      cationic antimicrobial peptides were examined: aurein 2.2, aurein 2.3 (almost
      identical to aurein 2.2, except for a point mutation at residue 13), and a
      carboxy C-terminal analog of aurein 2.3. Circular dichroism results indicated
      that all three peptides adopt an alpha-helical structure in the presence of a 3:1
      molar mixture of 1,2-dimyristoyl-sn-glycero-3-phosphocholine/1,2-dimyristoyl-sn
      glycero-3-[phospho-rac-(1-glycerol)] (DMPC/DMPG), and 1:1 and 3:1 molar mixtures
      of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn
      glycero-3-[phospho-rac-(1-glycerol)] (POPC/POPG). Oriented circular dichroism
      data for three different lipid compositions showed that all three peptides were
      surface-adsorbed at low peptide concentrations, but were inserted into the
      membrane at higher peptide concentrations. The (31)P solid-state NMR data of the
      three peptides in the DMPC/DMPG and POPC/POPG bilayers showed that all three
      peptides significantly perturbed lipid headgroups, in a peptide or lipid
      composition-dependent manner. Differential scanning calorimetry results
      demonstrated that both amidated aurein peptides perturbed the overall phase
      structure of DMPC/DMPG bilayers, but perturbed the POPC/POPG chains less. The
      nature of the perturbation of DMPC/DMPG bilayers was most likely micellization,
      and for the POPC/POPG bilayers, distorted toroidal pores or localized membrane
      aggregate formation. Calcein release assay results showed that aurein peptide
      induced membrane leakage was more severe in DMPC/DMPG liposomes than in POPC/POPG
      liposomes, and that aurein 2.2 induced higher calcein release than aurein 2.3 and
      aurein 2.3-COOH from 1:1 and 3:1 POPC/POPG liposomes. Finally, DiSC(3)5 assay
      data further delineated aurein 2.2 from the others by showing that it perturbed
      the lipid membranes of intact S. aureus C622 most efficiently, whereas aurein 2.3
      had the same efficiency as gramicidin S, and aurein 2.3-COOH was the least
      efficient. Taken together, these data show that the membrane interactions of
      aurein peptides are affected by the hydrophobic thickness of the lipid bilayers
      and the PG content.

PMID- 19167305
TI  - Single-molecule fluorescence studies of a PH domain: new insights into the
      membrane docking reaction.
AB  - Proteins containing membrane targeting domains play essential roles in many
      cellular signaling pathways. However, important features of the membrane-bound
      state are invisible to bulk methods, thereby hindering mechanistic analysis of
      membrane targeting reactions. Here we use total internal reflection fluorescence
      microscopy (TIRFM), combined with single particle tracking, to probe the membrane
      docking mechanism of a representative pleckstrin homology (PH) domain isolated
      from the general receptor for phosphoinositides, isoform 1 (GRP1). The findings
      show three previously undescribed features of GRP1 PH domain docking to membranes
      containing its rare target lipid, phosphatidylinositol (3,4,5)-trisphosphate
      [PI(3,4,5)P(3)]. First, analysis of surface diffusion kinetics on supported lipid
      bilayers shows that in the absence of other anionic lipids, the PI(3,4,5)P(3)
      bound protein exhibits the same diffusion constant as a single lipid molecule.
      Second, the binding of the anionic lipid phosphatidylserine to a previously
      unidentified secondary binding site slows both diffusion and dissociation
      kinetics. Third, TIRFM enables direct observation of rare events in which
      dissociation from the membrane surface is followed by transient diffusion through
      solution and rapid rebinding to a nearby, membrane-associated target lipid.
      Overall, this study shows that in vitro single-molecule TIRFM provides a new
      window into the molecular mechanisms of membrane docking reactions.

PMID- 19167306
TI  - The effect of myofilament compliance on kinetics of force generation by myosin
      motors in muscle.
AB  - We use the inhibitor of isometric force of skeletal muscle N-benzyl-p-toluene
      sulfonamide (BTS) to decrease, in a dose dependent way, the number of myosin
      motors attached to actin during the steady isometric contraction of single fibers
      from frog skeletal muscle (4 degrees C, 2.1 microm sarcomere length). In this way
      we can reduce the strain in the myofilament compliance during the isometric
      tetanus (T(0)) from 3.54 nm in the control solution (T(0,NR)) to approximately
      0.5 nm in 1 microM BTS, where T(0) is reduced to approximately 0.15 T(0,NR). The
      quick force recovery after a step release (1-3 nm per half-sarcomere) becomes
      faster with the increase of BTS concentration and the decrease of T(0). The
      simulation of quick force recovery with a multistate model of force generation,
      that adapts Huxley and Simmons model to account for both the high stiffness of
      the myosin motor (approximately 3 pN/nm) and the myofilament compliance, shows
      that the increase in the rate of quick force recovery by BTS is explained by the
      reduced strain in the myofilaments, consequent to the decrease in half-sarcomere
      force. The model estimates that i), for the same half-sarcomere release the state
      transition kinetics in the myosin motor are five times faster in the absence of
      filament compliance than in the control; and ii), the rate of force recovery from
      zero to T(0) is approximately 6000/s in the absence of filament compliance.

PMID- 19167307
TI  - Microscopic mechanics of hairpin DNA translocation through synthetic nanopores.
AB  - Nanoscale pores have proved useful as a means to assay DNA and are actively being
      developed as the basis of genome sequencing methods. Hairpin DNA (hpDNA), having
      both double-helical and overhanging coil portions, can be trapped in a nanopore,
      giving ample time to execute a sequence measurement. In this article, we provide
      a detailed account of hpDNA interaction with a synthetic nanopore obtained
      through extensive all-atom molecular dynamics simulations. For synthetic pores
      with minimum diameters from 1.3 to 2.2 nm, we find that hpDNA can translocate by
      three modes: unzipping of the double helix and--in two distinct orientations-
      stretching/distortion of the double helix. Furthermore, each of these modes can
      be selected by an appropriate choice of the pore size and voltage applied
      transverse to the membrane. We demonstrate that the presence of hpDNA can
      dramatically alter the distribution of ions within the pore, substantially
      affecting the ionic current through it. In experiments and simulations, the ionic
      current relative to that in the absence of DNA can drop below 10% and rise beyond
      200%. Simulations associate the former with the double helix occupying the
      constriction and the latter with accumulation of DNA that has passed through the
      constriction.

PMID- 19167308
TI  - Quantitative transcription factor binding kinetics at the single-molecule level.
AB  - We investigated the binding interaction between the bacteriophage lambda
      repressor CI and its target DNA using total internal reflection fluorescence
      microscopy. Large stepwise changes in the intensity of the red fluorescent
      protein fused to CI were observed as it associated with and dissociated from
      individually labeled single-molecule DNA targets. The stochastic association and
      dissociation were characterized by Poisson statistics. Dark and bright intervals
      were measured for thousands of individual events. The exponential distribution of
      the intervals allowed direct determination of the association and dissociation
      rate constants (k(a) and k(d), respectively). We resolved in detail how k(a) and
      k(d) varied as a function of three control parameters: the DNA length L, the CI
      dimer concentration, and the binding affinity. Our results show that although
      interactions with nonoperator DNA sequences are observable, CI binding to the
      operator site is not dependent on the length of flanking nonoperator DNA.

PMID- 19167309
TI  - Charge separation, stabilization, and protein relaxation in photosystem II core
      particles with closed reaction center.
AB  - The fluorescence kinetics of cyanobacterial photosystem II (PSII) core particles
      with closed reaction centers (RCs) were studied with picosecond resolution. The
      data are modeled in terms of electron transfer (ET) and associated protein
      conformational relaxation processes, resolving four different radical pair (RP)
      states. The target analyses reveal the importance of protein relaxation steps in
      the ET chain for the functioning of PSII. We also tested previously published
      data on cyanobacterial PSII with open RCs using models that involved protein
      relaxation steps as suggested by our data on closed RCs. The rationale for this
      reanalysis is that at least one short-lived component could not be described in
      the previous simpler models. This new analysis supports the involvement of a
      protein relaxation step for open RCs as well. In this model the rate of ET from
      reduced pheophytin to the primary quinone Q(A) is determined to be 4.1 ns(-1).
      The rate of initial charge separation is slowed down substantially from
      approximately 170 ns(-1) in PSII with open RCs to 56 ns(-1) upon reduction of
      Q(A). However, the free-energy drop of the first RP is not changed substantially
      between the two RC redox states. The currently assumed mechanistic model,
      assuming the same early RP intermediates in both states of RC, is inconsistent
      with the presented energetics of the RPs. Additionally, a comparison between PSII
      with closed RCs in isolated cores and in intact cells reveals slightly different
      relaxation kinetics, with a approximately 3.7 ns component present only in
      isolated cores.

PMID- 19167310
TI  - Inhibition of lactoperoxidase by its own catalytic product: crystal structure of
      the hypothiocyanate-inhibited bovine lactoperoxidase at 2.3-A resolution.
AB  - To the best of our knowledge, this is the first report on the structure of
      product-inhibited mammalian peroxidase. Lactoperoxidase is a heme containing an
      enzyme that catalyzes the inactivation of a wide range of microorganisms. In the
      presence of hydrogen peroxide, it preferentially converts thiocyanate ion into a
      toxic hypothiocyanate ion. Samples of bovine lactoperoxidase containing
      thiocyanate (SCN(-)) and hypothiocyanate (OSCN(-)) ions were purified and
      crystallized. The structure was determined at 2.3-A resolution and refined to
      R(cryst) and R(free) factors of 0.184 and 0.221, respectively. The determination
      of structure revealed the presence of an OSCN(-) ion at the distal heme cavity.
      The presence of OSCN(-) ions in crystal samples was also confirmed by chemical
      and spectroscopic analysis. The OSCN(-) ion interacts with the heme iron, Gln-105
      N(epsilon1), His-109 N(epsilon2), and a water molecule W96. The sulfur atom of
      the OSCN(-) ion forms a hypervalent bond with a nitrogen atom of the pyrrole ring
      D of the heme moiety at an S-N distance of 2.8 A. The heme group is covalently
      bound to the protein through two ester linkages involving carboxylic groups of
      Glu-258 and Asp-108 and the modified methyl groups of pyrrole rings A and C,
      respectively. The heme moiety is significantly distorted from planarity, whereas
      pyrrole rings A, B, C, and D are essentially planar. The iron atom is displaced
      by approximately 0.2 A from the plane of the heme group toward the proximal site.
      The substrate channel resembles a long tunnel whose inner walls contain
      predominantly aromatic residues such as Phe-113, Phe-239, Phe-254, Phe-380, Phe
      381, Phe-422, and Pro-424. A phosphorylated Ser-198 was evident at the surface,
      in the proximity of the calcium-binding channel.

PMID- 19167311
TI  - Fiber depolymerization: fracture, fragments, vanishing times, and stochastics in
      sickle hemoglobin.
AB  - The well-characterized rates, mechanisms, and stochastics of nucleation-dependent
      polymerization of deoxyhemoglobin S (HbS) are important in governing whether or
      not vaso-occlusive sickle cell crises will occur. The less well studied kinetics
      of depolymerization may also be important, for example in achieving full
      dissolution of polymers in the lungs, in resolution of crises and/or in
      minimizing gelation-induced cellular damage. We examine depolymerization by
      microscopic observations on depolymerizing HbS fibers, by Monte Carlo simulations
      and by analytical characterization of the mechanisms. We show that fibers
      fracture. Experimental scatter of rates is consistent with stochastic features of
      the analytical model and Monte Carlo results. We derive a model for the
      distribution of vanishing times and also show the distribution of fracture
      dependent fiber fragment lengths and its time dependence. We describe differences
      between depolymerization of single fibers and bundles and propose models for
      bundle dissolution. Our basic model can be extended to dissolution of gels
      containing many fibers and is also applicable to other reversible linear polymers
      that dissolve by random fracture and end-depolymerization. Under the model,
      conditions in which residual HbS polymers exist and facilitate repolymerization
      and thus pathology can be defined; whereas for normal polymers requiring cyclic
      polymerization and depolymerization for function, conditions for rapid cycling
      due to residual aggregates can be identified.

PMID- 19167312
TI  - Macromolecular crowding modulates folding mechanism of alpha/beta protein
      apoflavodoxin.
AB  - Protein dynamics in cells may be different from those in dilute solutions in
      vitro, because the environment in cells is highly concentrated with other
      macromolecules. This volume exclusion because of macromolecular crowding is
      predicted to affect both equilibrium and kinetic processes involving protein
      conformational changes. To quantify macromolecular crowding effects on protein
      folding mechanisms, we investigated the folding energy landscape of an alpha/beta
      protein, apoflavodoxin, in the presence of inert macromolecular crowding agents,
      using in silico and in vitro approaches. By means of coarse-grained molecular
      simulations and topology-based potential interactions, we probed the effects of
      increased volume fractions of crowding agents (phi(c)) as well as of crowding
      agent geometry (sphere or spherocylinder) at high phi(c). Parallel kinetic
      folding experiments with purified Desulfovibro desulfuricans apoflavodoxin in
      vitro were performed in the presence of Ficoll (sphere) and Dextran
      (spherocylinder) synthetic crowding agents. In conclusion, we identified the in
      silico crowding conditions that best enhance protein stability, and discovered
      that upon manipulation of the crowding conditions, folding routes experiencing
      topological frustrations can be either enhanced or relieved. Our test-tube
      experiments confirmed that apoflavodoxin's time-resolved folding path is
      modulated by crowding agent geometry. Macromolecular crowding effects may be a
      tool for the manipulation of protein-folding and function in living cells.

PMID- 19167313
TI  - Loop dynamics of the extracellular domain of human tissue factor and activation
      of factor VIIa.
AB  - In the crystal structure of the complex between the soluble extracellular domain
      of tissue factor (sTF) and active-site-inhibited VIIa, residues 91 and 92 in the
      Pro(79)-Pro(92) loop of sTF interact with the catalytic domain of VIIa. It is not
      known, however, whether this loop has a role in allosteric activation of VIIa.
      Time-resolved fluorescence anisotropy measurements of probes covalently bound to
      sTF mutants E84C and T121C show that binding uninhibited Factor VIIa affects
      segmental motions in sTF. Glu(84) resides in the Pro(79)-Pro(92) loop, and
      Thr(121) resides in the turn between the first and second antiparallel beta
      strands of the sTF subdomain that interacts with the Gla and EGF1 domains of
      VIIa; neither Glu(84) nor Thr(121) makes direct contact with VIIa. Probes bound
      to T121C report limited segmental flexibility in free sTF, which is lost after
      VIIa binding. Probes bound to E84C report substantial segmental flexibility in
      the Pro(79)-Pro(92) loop in free sTF, which is greatly reduced after VIIa
      binding. Thus, VIIa binding reduces dynamic motions in sTF. In particular, the
      decrease in the Pro(79)-Pro(92) loop motions indicates that loop entropy has a
      role in the thermodynamics of the protein-protein interactions involved in
      allosteric control of VIIa activation.

PMID- 19167314
TI  - Casein micelle dispersions under osmotic stress.
AB  - Casein micelles dispersions have been concentrated and equilibrated at different
      osmotic pressures using equilibrium dialysis. This technique measured an equation
      of state of the dispersions over a wide range of pressures and concentrations and
      at different ionic strengths. Three regimes were found. i), A dilute regime in
      which the osmotic pressure is proportional to the casein concentration. In this
      regime, the casein micelles are well separated and rarely interact, whereas the
      osmotic pressure is dominated by the contribution from small residual peptides
      that are dissolved in the aqueous phase. ii), A transition range that starts when
      the casein micelles begin to interact through their kappa-casein brushes and ends
      when the micelles are forced to get into contact with each other. At the end of
      this regime, the dispersions behave as coherent solids that do not fully
      redisperse when osmotic stress is released. iii), A concentrated regime in which
      compression removes water from within the micelles, and increases the fraction of
      micelles that are irreversibly linked to each other. In this regime the osmotic
      pressure profile is a power law of the residual free volume. It is well described
      by a simple model that considers the micelle to be made of dense regions
      separated by a continuous phase. The amount of water in the dense regions matches
      the usual hydration of proteins.

PMID- 19167315
TI  - Detecting protein complexes in living cells from laser scanning confocal image
      sequences by the cross correlation raster image spectroscopy method.
AB  - We describe a general method for detecting molecular complexes based on the
      analysis of single molecule fluorescence fluctuations from laser scanning
      confocal images. The method detects and quantifies complexes of two different
      fluorescent proteins noninvasively in living cells. Because in a raster scanned
      image successive pixels are measured at different times, the spatial correlation
      of the image contains information about dynamic processes occurring over a large
      time range, from the microseconds to seconds. The correlation of intensity
      fluctuations measured simultaneously in two channels detects protein complexes
      that carry two molecules of different colors. This information is obtained from
      the entire image. A map of the spatial distribution of protein complexes in the
      cell and their diffusion and/or binding properties can be constructed. Using this
      cross correlation raster image spectroscopy method, specific locations in the
      cell can be visualized where dynamics of binding and unbinding of fluorescent
      protein complexes occur. This fluctuation imaging method can be applied to
      commercial laser scanning microscopes thereby making it accessible to a large
      community of scientists.

PMID- 19167316
TI  - Regulation of cell cytoskeleton and membrane mechanics by electric field: role of
      linker proteins.
AB  - Cellular mechanics is known to play an important role in the cell homeostasis
      including proliferation, motility, and differentiation. Significant variation in
      the mechanical properties between different cell types suggests that control of
      the cell metabolism is feasible through manipulation of the cell mechanical
      parameters using external physical stimuli. We investigated the electrocoupling
      mechanisms of cellular biomechanics modulation by an electrical stimulation in
      two mechanically distinct cell types--human mesenchymal stem cells and
      osteoblasts. Application of a 2 V/cm direct current electric field resulted in
      approximately a twofold decrease in the cell elasticity and depleted
      intracellular ATP. Reduction in the ATP level led to inhibition of the linker
      proteins that are known to physically couple the cell membrane and cytoskeleton.
      The membrane separation from the cytoskeleton was confirmed by up to a twofold
      increase in the membrane tether length that was extracted from the cell membrane
      after an electrical stimulation. In comparison to human mesenchymal stem cells,
      the membrane-cytoskeleton attachment in osteoblasts was much stronger but, in
      response to the same electrical stimulation, the membrane detachment from the
      cytoskeleton was found to be more pronounced. The observed effects mediated by an
      electric field are cell type- and serum-dependent and can potentially be used for
      electrically assisted cell manipulation. An in-depth understanding and control of
      the mechanisms to regulate cell mechanics by external physical stimulus (e.g.,
      electric field) may have great implications for stem cell-based tissue
      engineering and regenerative medicine.

PMID- 19167317
TI  - Cell traction forces direct fibronectin matrix assembly.
AB  - Interactions between cells and the surrounding matrix are critical to the
      development and engineering of tissues. We have investigated the role of cell
      derived traction forces in the assembly of extracellular matrix using what we
      believe is a novel assay that allows for simultaneous measurement of traction
      forces and fibronectin fibril growth at discrete cell-matrix attachment sites.
      NIH3T3 cells were plated onto arrays of deformable cantilever posts for 2-24 h.
      Data indicate that developing fibril orientation is guided by the direction of
      the traction force applied to that fibril. In addition, cells initially establish
      a spatial distribution of traction forces that is largest at the cell edge and
      decreases toward the cell center. This distribution progressively shifts from a
      predominantly peripheral pattern to a more uniform pattern as compressive strain
      at the cell perimeter decreases with time. The impact of these changes on
      fibrillogenesis was tested by treating cells with blebbistatin or calyculin A to
      tonically block or augment, respectively, myosin II activity. Both treatments
      blocked the inward translation of traction forces, the dissipation of compressive
      strain, and fibronectin fibrillogenesis over time. These data indicate that
      dynamic spatial and temporal changes in traction force and local strain may
      contribute to successful matrix assembly.

PMID- 19167318
TI  - Fast electromechanical amplification in the lateral membrane of the outer hair
      cell.
AB  - Outer hair cells provide amplification within the mammalian cochlea to enhance
      audition. The mechanism is believed to reside within the lateral membrane of the
      cell that houses an expansive array of molecular motors, identified as prestin,
      which drives somatic electromotility. By measuring nonlinear capacitance, the
      electrical signature of electromotility, at kilohertz rates we have uncovered new
      details of the early molecular events that arise from voltage perturbations of
      prestin. We show that dynamic changes in motor state probability occur within the
      kilohertz range, and signify an amplificatory event. Additionally, we show a lack
      of effect of Cl driving force, an absence of cell length effect (indicating that
      the kinetics does not vary across auditory frequency), and the first
      demonstration of the time dependence of tension induced amplificatory shifts. The
      process we have identified, where the stimulus-response function shifts in time
      along the stimulus axis in a multi-exponential manner, bears similarities to
      those components of adaptation found in the OHC stereociliar transducer
      identified recently. As with the forward transducer, the speed of the reverse
      transducer amplificatory event consequently impacts on high frequency peripheral
      auditory processing.

PMID- 19167319
TI  - Effects on conformational states of the rabbit sodium/glucose cotransporter
      through modulation of polarity and charge at glutamine 457.
AB  - The high affinity sodium/glucose cotransporter (SGLT1) couples transport of Na(+)
      and glucose. Previous studies established that mutant Q457C human SGLT1 retains
      full activity, and sugar translocation is abolished in mutant Q457R or in mutant
      Q457C after reaction with methanethiosulfonate derivatives, but Na(+) and sugar
      binding remain intact. To explore the mechanism by which modulation of Q457
      abolishes transport, Q457C and Q457R of rabbit SGLT1 were studied using chemical
      modification and the two-electrode voltage-clamp technique. Compared to wild-type
      SGLT1, Q457C exhibits approximately 20-fold reduction in phloridzin affinity and
      preferential occupancy of an inward-facing state. Alkylation of Q457C by [(2
      trimethylammonium) ethyl] methanethiosulphonate bromide, (MTSET), reverses these
      changes while blocking transport. Analysis of pre-steady-state currents in the
      absence of sugar yields three decay constants for each of Q457C, Q457C-MTSET and
      Q457R. Comparison of Q457C-MTSET and Q457R with Q457C and wild-type, reveals that
      inhibition of transport is accompanied by a decrease in magnitude and voltage
      independence of the slow decay constant at negative potentials. But fast and
      medium decays remain unchanged. Computer simulation of transient currents
      suggests that introduction of positive charge at position 457 leads to a
      predominant outward rather than inward-facing conformational state. Taken
      together, the results suggest that glutamine 457, in addition to being involved
      in sugar binding, is a residue that is sensitive to conformational changes of the
      carrier.

PMID- 19167321
TI  - Understanding the words of chromatin regulation.
AB  - Recent studies indicate that chromatin regulatory complexes produce biological
      specificity in the way that letters produce meanings by combinations into words.
      Combinatorial assembly of chromatin regulatory complexes may be critical for
      maximizing the information content provided by arrays of histone modifications.

PMID- 19167322
TI  - Autophagy SEPArates germline and somatic cells.
AB  - Cellular determinants of the germline selectively accumulate in germ cell
      precursors and influence cell fate during early development in many organisms.
      Zhang et al. (2009) now report that targeted autophagy mediated by the SEPA-1
      protein depletes germplasm proteins from somatic cells during early development
      of the nematode.

PMID- 19167323
TI  - p38delta and PKD1: kinase switches for insulin secretion.
AB  - Insufficient production of the hormone insulin by pancreatic beta cells results
      in diabetes. In this issue, Sumara et al. (2009) report key roles for the protein
      kinases p38delta and PKD1 in the regulation of insulin secretion as well as in
      the survival of pancreatic beta cells.

PMID- 19167324
TI  - Old nuclei spring new leaks.
AB  - The nuclear pore complex (NPC) regulates the bidirectional movement of cell
      components across the nuclear envelope. In this issue, D'Angelo et al. (2009)
      demonstrate that the NPC loses essential protein subunits as cells age, resulting
      in increased nuclear permeability and potentially contributing to organismal
      aging.

PMID- 19167325
TI  - The PTP family photo album.
AB  - Protein tyrosine phosphatases (PTPs) are central players in many biological
      processes. In this issue, Barr et al. (2009) analyze 22 different PTP structures
      to define their common and unique features. This effort provides key insights
      into the regulation of PTP activity that could lead to the development of new
      therapeutics.

PMID- 19167326
TI  - MicroRNAs: target recognition and regulatory functions.
AB  - MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important
      gene-regulatory roles in animals and plants by pairing to the mRNAs of protein
      coding genes to direct their posttranscriptional repression. This review outlines
      the current understanding of miRNA target recognition in animals and discusses
      the widespread impact of miRNAs on both the expression and evolution of protein
      coding genes.

PMID- 19167328
TI  - The native 3D organization of bacterial polysomes.
AB  - Recent advances have led to insights into the structure of the bacterial
      ribosome, but little is known about the 3D organization of ribosomes in the
      context of translating polysomes. We employed cryoelectron tomography and a
      template-matching approach to map 70S ribosomes in vitrified bacterial
      translation extracts and in lysates of active E. coli spheroplasts. In these
      preparations, polysomal arrangements were observed in which neighboring ribosomes
      are densely packed and exhibit preferred orientations. Analysis of characteristic
      examples of polysomes reveals a staggered or pseudohelical organization of
      ribosomes along the mRNA trace, with the transcript being sequestered on the
      inside, the tRNA entrance sites being accessible, and the polypeptide exit sites
      facing the cytosol. Modeling of elongating nascent polypeptide chains suggests
      that this arrangement maximizes the distance between nascent chains on adjacent
      ribosomes, thereby reducing the probability of intermolecular interactions that
      would give rise to aggregation and limit productive folding.

PMID- 19167327
TI  - Induction of hepatitis by JNK-mediated expression of TNF-alpha.
AB  - The c-Jun NH(2)-terminal kinase (JNK) signaling pathway has been implicated in
      the development of tumor necrosis factor (TNF)-dependent hepatitis. JNK may play
      a critical role in hepatocytes during TNF-stimulated cell death in vivo. To test
      this hypothesis, we examined the phenotype of mice with compound disruption of
      the Jnk1 and Jnk2 genes. Mice with loss of JNK1/2 expression in hepatocytes
      exhibited no defects in the development of hepatitis compared with control mice,
      whereas mice with loss of JNK1/2 in the hematopoietic compartment exhibited a
      profound defect in hepatitis that was associated with markedly reduced expression
      of TNF-alpha. These data indicate that JNK is required for TNF-alpha expression
      but not for TNF-alpha-stimulated death of hepatocytes. Indeed, TNF-alpha induced
      similar hepatic damage in both mice with hepatocyte-specific JNK1/2 deficiency
      and control mice. These observations confirm a role for JNK in the development of
      hepatitis but identify hematopoietic cells as the site of the essential function
      of JNK.

PMID- 19167330
TI  - Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear
      integrity in postmitotic cells.
AB  - In dividing cells, nuclear pore complexes (NPCs) disassemble during mitosis and
      reassemble into the newly forming nuclei. However, the fate of nuclear pores in
      postmitotic cells is unknown. Here, we show that NPCs, unlike other nuclear
      structures, do not turn over in differentiated cells. While a subset of NPC
      components, like Nup153 and Nup50, are continuously exchanged, scaffold
      nucleoporins, like the Nup107/160 complex, are extremely long-lived and remain
      incorporated in the nuclear membrane during the entire cellular life span.
      Besides the lack of nucleoporin expression and NPC turnover, we discovered an age
      related deterioration of NPCs, leading to an increase in nuclear permeability and
      the leaking of cytoplasmic proteins into the nucleus. Our finding that nuclear
      "leakiness" is dramatically accelerated during aging and that a subset of
      nucleoporins is oxidatively damaged in old cells suggests that the accumulation
      of damage at the NPC might be a crucial aging event.

PMID- 19167329
TI  - Cotranslational and posttranslational N-glycosylation of polypeptides by distinct
      mammalian OST isoforms.
AB  - Asparagine-linked glycosylation of polypeptides in the lumen of the endoplasmic
      reticulum is catalyzed by the hetero-oligomeric oligosaccharyltransferase (OST).
      OST isoforms with different catalytic subunits (STT3A versus STT3B) and distinct
      enzymatic properties are coexpressed in mammalian cells. Using siRNA to achieve
      isoform-specific knockdowns, we show that the OST isoforms cooperate and act
      sequentially to mediate protein N-glycosylation. The STT3A OST isoform is
      primarily responsible for cotranslational glycosylation of the nascent
      polypeptide as it enters the lumen of the endoplasmic reticulum. The STT3B
      isoform is required for efficient cotranslational glycosylation of an acceptor
      site adjacent to the N-terminal signal sequence of a secreted protein. Unlike
      STT3A, STT3B efficiently mediates posttranslational glycosylation of a carboxyl
      terminal glycosylation site in an unfolded protein. These distinct and
      complementary roles for the OST isoforms allow sequential scanning of
      polypeptides for acceptor sites to insure the maximal efficiency of N
      glycosylation.

PMID- 19167331
TI  - Interpretation of the wingless gradient requires signaling-induced self
      inhibition.
AB  - In a classical view of development, a cell can acquire positional information by
      reading the local concentration of a morphogen independently of its neighbors.
      Accordingly, in Drosophila, the morphogen Wingless produced in the wing's
      prospective distal region activates target genes in a dose-dependent fashion to
      organize the proximodistal pattern. Here, we show that, in parallel, Wingless
      triggers two nonautonomous inhibitory programs that play an important role in the
      establishment of positional information. Cells flanking the source of Wingless
      produce a negative signal (encoded by notum) that inhibits Wingless signaling in
      nearby cells. Additionally, in response to Wingless, all prospective wing cells
      produce an unidentified signal that dampens target gene expression in surrounding
      cells. Thus, cells influence each other's response to Wingless through at least
      two modes of lateral inhibition. Without lateral inhibition, some cells acquire
      ectopic fates. Lateral inhibition may be a general mechanism behind the
      interpretation of morphogen gradients.

PMID- 19167332
TI  - SEPA-1 mediates the specific recognition and degradation of P granule components
      by autophagy in C. elegans.
AB  - How autophagy, an evolutionarily conserved intracellular catabolic system for
      bulk degradation, selectively degrades protein aggregates is poorly understood.
      Here, we show that several maternally derived germ P granule components are
      selectively eliminated by autophagy in somatic cells during C. elegans
      embryogenesis. The activity of sepa-1 is required for the degradation of these P
      granule components and for their accumulation into aggregates, termed PGL
      granules, in autophagy mutants. SEPA-1 forms protein aggregates and is also a
      preferential target of autophagy. SEPA-1 directly binds to the P granule
      component PGL-3 and also to the autophagy protein LGG-1/Atg8. SEPA-1 aggregates
      consistently colocalize with PGL granules and with LGG-1 puncta. Thus, SEPA-1
      functions as a bridging molecule in mediating the specific recognition and
      degradation of P granule components by autophagy. Our study reveals a mechanism
      for preferential degradation of protein aggregates by autophagy and emphasizes
      the physiological significance of selective autophagy during animal development.

PMID- 19167333
TI  - A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic
      neurons.
AB  - The ubiquitin ligase anaphase-promoting complex (APC) recruits the coactivator
      Cdc20 to drive mitosis in cycling cells. However, the nonmitotic functions of
      Cdc20-APC have remained unexplored. We report that Cdc20-APC plays an essential
      role in dendrite morphogenesis in postmitotic neurons. Knockdown of Cdc20 in
      cerebellar slices and in postnatal rats in vivo profoundly impairs the formation
      of granule neuron dendrite arbors in the cerebellar cortex. Remarkably, Cdc20 is
      enriched at the centrosome in neurons, and the centrosomal localization is
      critical for Cdc20-dependent dendrite development. We also find that the
      centrosome-associated protein histone deacetylase 6 (HDAC6) promotes the
      polyubiquitination of Cdc20, stimulates the activity of centrosomal Cdc20-APC,
      and drives the differentiation of dendrites. These findings define a postmitotic
      function for Cdc20-APC in the morphogenesis of dendrites in the mammalian brain.
      The identification of a centrosomal Cdc20-APC ubiquitin signaling pathway holds
      important implications for diverse biological processes, including neuronal
      connectivity and plasticity.

PMID- 19167334
TI  - Digital signaling and hysteresis characterize ras activation in lymphoid cells.
AB  - Activation of Ras proteins underlies functional decisions in diverse cell types.
      Two molecules, RasGRP and SOS, catalyze Ras activation in lymphocytes. Binding of
      active Ras to SOS' allosteric pocket markedly increases SOS' activity
      establishing a positive feedback loop for SOS-mediated Ras activation.
      Integrating in silico and in vitro studies, we demonstrate that digital signaling
      in lymphocytes (cells are "on" or "off") is predicated upon feedback regulation
      of SOS. SOS' feedback loop leads to hysteresis in the dose-response curve, which
      can enable a capacity to sustain Ras activation as stimuli are withdrawn and
      exhibit "memory" of past encounters with antigen. Ras activation via RasGRP alone
      is analog (graded increase in amplitude with stimulus). We describe how
      complementary analog (RasGRP) and digital (SOS) pathways act on Ras to
      efficiently convert analog input to digital output. Numerous predictions
      regarding the impact of our findings on lymphocyte function and development are
      noted.

PMID- 19167335
TI  - Large-scale structural analysis of the classical human protein tyrosine
      phosphatome.
AB  - Protein tyrosine phosphatases (PTPs) play a critical role in regulating cellular
      functions by selectively dephosphorylating their substrates. Here we present 22
      human PTP crystal structures that, together with prior structural knowledge,
      enable a comprehensive analysis of the classical PTP family. Despite their
      largely conserved fold, surface properties of PTPs are strikingly diverse. A
      potential secondary substrate-binding pocket is frequently found in phosphatases,
      and this has implications for both substrate recognition and development of
      selective inhibitors. Structural comparison identified four diverse catalytic
      loop (WPD) conformations and suggested a mechanism for loop closure. Enzymatic
      assays revealed vast differences in PTP catalytic activity and identified PTPD1,
      PTPD2, and HDPTP as catalytically inert protein phosphatases. We propose a "head
      to-toe" dimerization model for RPTPgamma/zeta that is distinct from the
      "inhibitory wedge" model and that provides a molecular basis for inhibitory
      regulation. This phosphatome resource gives an expanded insight into intrafamily
      PTP diversity, catalytic activity, substrate recognition, and autoregulatory self
      association.

PMID- 19167337
TI  - SnapShot: Microtubule Regulators I.

PMID- 19167336
TI  - Role of the murine reprogramming factors in the induction of pluripotency.
AB  - Induced pluripotent stem (iPS) cells can be obtained from fibroblasts upon
      expression of Oct4, Sox2, Klf4, and c-Myc. To understand how these factors induce
      pluripotency, we carried out genome-wide analyses of their promoter binding and
      expression in iPS and partially reprogrammed cells. We find that target genes of
      the four factors strongly overlap in iPS and embryonic stem (ES) cells. In
      partially reprogrammed cells, many genes co-occupied by c-Myc and any of the
      other three factors already show an ES cell-like binding and expression pattern.
      In contrast, genes that are specifically co-bound by Oct4, Sox2, and Klf4 in ES
      cells and encode pluripotency regulators severely lack binding and
      transcriptional activation. Among the four factors, c-Myc promotes the most ES
      cell-like transcription pattern when expressed individually in fibroblasts. These
      data uncover temporal and separable contributions of the four factors during the
      reprogramming process and indicate that ectopic c-Myc predominantly acts before
      pluripotency regulators are activated.

PMID- 19167338
TI  - Application of gelatin-coated magnetic particles for isolation of genomic DNA
      from bacterial cells.
AB  - Gelatin-coated magnetic particles were implemented for bacterial genomic DNA
      isolation in this study. Based on structural differences in the cell wall, the
      standard strains Staphylococcus aureus and Escherichia coli were selected. The
      quantity, quality, and timing process for DNA extraction using gelatin-coated
      magnetite were compared to reference phenol-chloroform extraction and a
      commercially available kit. Approximately twice as much DNA was recovered with
      the use of coated magnetite, providing greater yields than other DNA extraction
      methods. In addition, the DNA quality was determined using 16S ribosomal DNA
      (rDNA) gene amplification by polymerase chain reaction (PCR). The described
      technique is rapid, simple, and a well-suited method to use with PCR for
      diagnosis of bacterial infections.

PMID- 19167339
TI  - Efficient cleavage of problematic tobacco etch virus (TEV)-protein arginine
      methyltransferase constructs.
AB  - Protein arginine methyltransferases (PRMTs) are enzymes that are involved in many
      biological processes. Several studies have shown that the identity of the N
      terminal fusion tag affects the substrate selectivity of PRMTs. Therefore, to
      accurately study substrate recognition, it is imperative that a tagless PRMT be
      used. However, cleavage of tagged PRMTs has been problematic. We have developed a
      successful method by which untagged PRMTs can be made using a tobacco etch virus
      (TEV) cleavage site at the N-terminal domain. This method may be useful for
      cleaving other challenging target proteins that have the TEV protease recognition
      site.

PMID- 19167340
TI  - High-performance capillary electrophoretic method for the quantification of
      global DNA methylation: application to methotrexate-resistant cells.
AB  - Global DNA hypomethylation in tumor tissue is a common characteristic in a
      variety of malignancies such as breast, colon, oral, lung, and blood cancers. A
      rapid and sensitive method has been developed for the determination of global DNA
      methylation in cells. Five substances--2'-deoxycytidine (dC), 5-methyl 2'
      deoxycytidine (mdC), 2'-deoxyadenosine (dA), 2'-deoxythymidine (dT), and 2'
      deoxyguanosine (dG)--were completely separated by high-performance capillary
      electrophoresis in 10 min. Intraday coefficient of variation was less than 1%,
      and interday coefficient of variation was less than 2%. The minimal detection
      limit was 1 microM. Acquired drug resistance to methotrexate (MTX) is one of the
      most serious problems in cancer chemotherapy. Under optimal conditions, we
      analyzed global DNA methylation levels in A549 and A549/MTX cells, and only 10(5)
      cells are needed to obtain reliable results. The percentage of 5-methyl-2'
      deoxycytidine (5-mC) was 4.80+/-0.52% in A549 cells, and this decreased to 4.20+/
      0.44% in A549/MTX cells. It was considered as statistically significant. This
      demonstrated that the mechanisms of acquired drug resistance to MTX might be
      concerned with DNA methylation.

PMID- 19167341
TI  - The ins and outs of Na(+) bioenergetics in Acetobacterium woodii.
AB  - The acetogenic bacterium Acetobacterium woodii uses a transmembrane
      electrochemical sodium ion potential for bioenergetic reactions. A primary sodium
      ion potential is established during carbonate (acetogenesis) as well as caffeate
      respiration. The electrogenic Na(+) pump connected to the Wood-Ljungdahl pathway
      (acetogenesis) still remains to be identified. The pathway of caffeate reduction
      with hydrogen as electron donor was investigated and the only membrane-bound
      activity was found to be a ferredoxin-dependent NAD(+) reduction. This exergonic
      electron transfer reaction may be catalyzed by the membrane-bound Rnf complex
      that was discovered recently and is suggested to couple exergonic electron
      transfer from ferredoxin to NAD(+) to the vectorial transport of Na(+) across the
      cytoplasmic membrane. Rnf may also be involved in acetogenesis. The
      electrochemical sodium ion potential thus generated is used to drive endergonic
      reactions such as flagellar rotation and ATP synthesis. The ATP synthase is a
      member of the F(1)F(O) class of enzymes but has an unusual and exceptional
      feature. Its membrane-embedded rotor is a hybrid made of F(O) and V(O)-like
      subunits in a stoichiometry of 9:1. This stoichiometry is apparently not variable
      with the growth conditions. The structure and function of the Rnf complex and the
      Na(+) F(1)F(O) ATP synthase as key elements of the Na(+) cycle in A. woodii are
      discussed.

PMID- 19167342
TI  - The YheI/YheH heterodimer from Bacillus subtilis is a multidrug ABC transporter.
AB  - ABC (ATP-binding cassette) transporters form the largest family of membrane
      proteins in micro-organisms where they are able to transport a wide variety of
      substrates against a concentration gradient, in an ATP-dependent process. Two
      genes from the same putative Bacillus subtilis operon, yheI and yheH, encoding
      possibly two different ABC transporters, were overexpressed in Escherichia coli
      in high yield, either separately or jointly. Using membrane vesicles, it is shown
      here that both subunits were required to detect, (i) the transport of four
      structurally unrelated drugs, and (ii) a vanadate-sensitive ATPase activity.
      Mutation of the invariant Walker-A lysine to an alanine residue in both subunits
      led to an inactive transporter. Moreover, after membrane solubilization by
      detergent, both wild-type subunits co-purified on a Ni-Agarose affinity column
      while only the YheH subunit contained a hexa-histidine tag. This shows that YheI
      and YheH are indeed able to interact together to form a heterodimer. Importantly,
      expression of both yheI and yheH genes in B. subtilis could be strongly
      stimulated by addition of sub-inhibitory concentrations of various unrelated
      antibiotics. Therefore, B. subtilis YheI/YheH forms a new heterodimeric multidrug
      ABC transporter possibly involved in multiple antibiotic resistance in vivo.

PMID- 19167343
TI  - Quantum calculations on water in the KcsA channel cavity with permeant and non
      permeant ions.
AB  - Different ions in the pore of the KcsA channel behave differently, and we relate
      this to their solvation. We show that the selectivity is dependent, in part, on
      the solvation in the cavity (sometimes referred to as the vestibule, it is the
      region containing water molecules between the intracellular gate and the
      selectivity filter at the extracellular end of the pore). We have shown earlier
      that potassium is more dependent at the upper end of the cavity region on
      solvation by the threonines there, while sodium ion has more water molecules as
      ligands. In addition, sodium ion is placed asymmetrically, while potassium is
      nearly exactly symmetric with respect to the four-fold symmetry of the channel.
      We have now extended these calculations to rubidium and cesium ions, and find
      that rubidium solvation resembles that of potassium (and both are permeant ions),
      while cesium resembles sodium (and both are non-permeant), in terms of the
      geometry of up to eight hydrating, and four non-hydrating, water molecules. In
      each case, a maximum of 12 water molecules are relevant to the calculation. The
      placement of the water molecules in the two cases is essentially the same as
      found from the electron density in the X-ray structure of Zhou and MacKinnon. For
      Na(+) and K(+), we show that energy decreases from bulk to the cavity to the
      lowest position in the selectivity filter (accurate energy could not be
      calculated for the heavier ions). A separate calculation shows that fixing the
      Na(+) ion at the position of the K(+) minimum, followed by re-optimization
      produced a significantly modified system, not something that could be produced by
      thermal fluctuations. Moving the K(+) into the Na(+) position in the upper cavity
      led to a small increase in energy, approximately 3 k(B)T, but was accompanied by
      large shifts in the positions of hydrating waters, which would create a major
      kinetic barrier. Therefore, thermal fluctuations could not invalidate the
      conclusions of the main calculations.

PMID- 19167344
TI  - Comparison of functional non-glycosylated GPCRs expression in Pichia pastoris.
AB  - N-linked glycosylation is the most common post-translational modification of G
      protein-coupled receptors (GPCRs) and is correlated to the localization and
      function of the receptors depending on each receptor. However, heterogeneity of
      glycosylation can interfere with protein crystallization. The removal of N-linked
      glycosylation from membrane proteins improves the ability to crystallize these
      proteins. We screened 25 non-glycosylated GPCRs for functional receptor
      production in the methylotrophic yeast Pichia pastoris using specific ligand
      receptor binding assays. We found that five clones were expressed at greater than
      10 pmol/mg, 9 clones at 1-10 pmol/mg and 11 clones at less than 1 pmol/mg of
      membrane protein. Further optimization of culture parameters including culture
      scale, induction time, pH and temperature enabled us to achieve expression of a
      functional human muscarinic acetylcholine receptor subtype 2 (CHRM2) with a
      B(max) value of 51.2 pmol/mg of membrane protein. Approximately 1.9 mg of the
      human CHRM2 was produced from a 1-L culture.

PMID- 19167345
TI  - Gain-of-function mutation of Nav1.5 in atrial fibrillation enhances cellular
      excitability and lowers the threshold for action potential firing.
AB  - Genetic mutations of the cardiac sodium channel (SCN5A) specific only to the
      phenotype of atrial fibrillation have recently been described. However, data on
      the biophysical properties of SCN5A variants associated with atrial fibrillation
      are scarce. In a mother and son with lone atrial fibrillation, we identified a
      novel SCN5A coding variant, K1493R, which altered a highly conserved residue in
      the DIII-IV linker and was located six amino acids downstream from the fast
      inactivation motif of sodium channels. Biophysical studies of K1493R in tsA201
      cells demonstrated a significant positive shift in voltage-dependence of
      inactivation and a large ramp current near resting membrane potential, indicating
      a gain-of-function. Enhanced cellular excitability was observed in transfected HL
      1 atrial cardiomyocytes, including spontaneous action potential depolarizations
      and a lower threshold for action potential firing. These novel biophysical
      observations provide molecular evidence linking cellular "hyperexcitability" as a
      mechanism inducing vulnerability to this common arrhythmia.

PMID- 19167346
TI  - A novel function for dendritic cell: clearance of VEGF via VEGF receptor-1.
AB  - It has been reported that the plasma levels of VEGF in tumor patients decreased
      during dendritic cell (DC)-based immunotherapy, but the underlying mechanism
      remains unclear. Our current report demonstrates that VEGF levels were
      significantly decreased in the supernatants of DCs incubated with rhVEGF or tumor
      conditioned medium (TCM) while the intracellular VEGF in DCs was increased. The
      increased intracellular VEGF was not due to the de novo VEGF synthesis by DCs
      because exogenous VEGF inhibited the mRNA expression of VEGF in DCs. More direct
      evidence was provided to demonstrate that Cy3-labeled VEGF could be internalized
      by DCs specifically and efficiently. In addition, the activity of DCs to
      internalize VEGF was abolished by neutralizing antibody against VEGF receptor-1
      (Flt-1) and inhibitors of endocytosis such as carbonyl cyanide m-chlorophenyl
      hydrazone (CCCP) and genistein. This study highlights a novel function of DCs and
      allows a better understanding of the DC-VEGF interaction.

PMID- 19167347
TI  - Fluorophore-quencher pair for monitoring protein motion.
AB  - A fluorophore/quencher pair capable of detecting conformational changes of DNA
      protein complexes is described. The system employs a fluorescent nucleoside
      analog 1,3-diaza-2-oxophenothiazine (tC) within duplex DNA and a non-fluorescent
      quencher (TEMPO) attached to an engineered cysteine residue of the protein. The
      straightforward labeling methodology allows for the placement of the fluorophore
      and quencher moieties at specific positions suited to studying the conformational
      change of interest. To illustrate the utility of the tC-TEMPO pair, we have
      monitored nucleotide-induced conformational changes of the Klenow fragment (KF)
      polymerase bound to duplex DNA. In this system, tC was incorporated in the primer
      strand of the duplex, adjacent to the 3' end, while TEMPO was positioned at the
      end of the O-helix within the fingers domain of KF. Using steady-state
      fluorescence spectroscopy, we measured the quenching efficiency in a binary
      complex of tC-modified DNA and TEMPO-labeled KF and in ternary complexes
      containing cognate or non-cognate dNTP substrates. The quenching efficiency is
      significantly enhanced in the presence of a cognate dNTP, indicating that the O
      helix has moved closer towards the DNA. In contrast, no significant tC quenching
      is observed in the presence of a non-cognate dNTP, indicating that the O-helix
      remains in a position that is beyond the distance reporting range of the tC-TEMPO
      pair. These results demonstrate that a cognate dNTP substrate induces a large
      conformational change of the O-helix, which can be sensitively detected using the
      tC-TEMPO pair. This fluorophore/quencher pair may be useful to study
      conformational changes associated with other DNA-enzyme complexes.

PMID- 19167348
TI  - MicroRNA-146a modulates human bronchial epithelial cell survival in response to
      the cytokine-induced apoptosis.
AB  - MicroRNA plays an important role in cell differentiation, proliferation and cell
      death. The current study found that miRNA-146a was up-regulated in human
      bronchial epithelial cells (HBECs) in response to stimulation by TGF-beta1 plus
      cytomix (a mixture of IL-1beta, IFN-gamma and TNF-alpha). TGF-beta1 plus cytomix
      (TCM) induced apoptosis in HBECs (3.4+/-0.6% of control vs 83.1+/-4.0% of TCM
      treated cells, p<0.01), and this was significantly blocked by the miRNA-146a
      mimic (8.8+/-1.5%, p<0.01). In contrast, a miRNA-146a inhibitor had only a modest
      effect on cell survival but appeared to augment the induction of epithelial
      mesenchymal transition (EMT) in response to the cytokines. The MicroRNA-146a
      mimic appears to modulate HBEC survival through a mechanism of up-regulating Bcl
      XL and STAT3 phosphorylation, and by this mechanism it could contribute to tissue
      repair and remodeling.

PMID- 19167349
TI  - Centromeric interval of chromosome 4 derived from C57BL/6 mice accelerates type 1
      diabetes in NOD.CD72b congenic mice.
AB  - The nonobese diabetic (NOD) mouse is a useful model of autoimmune type 1 diabetes
      exhibiting many similarities to human type 1 diabetes patients including the
      presence of auto-reactive T cells and pancreas-specific autoantiboies. Multiple
      Idd loci control the development of diabetes in NOD mice. CD72, a B cell membrane
      bound glycoprotein carrying a C-type lectin-like domain, is an inhibitory co
      receptor of the B cell antigen receptor (BCR) that negatively regulates BCR
      signaling. Among four known haplotypes of mouse CD72, NOD mice carry the CD72(c)
      haplotype, whereas most of the other inbred strains of mice carry either CD72(a)
      or CD72(b). In this study, we generated congenic NOD.CD72(b) mice that carry
      C57BL/6 (B6) mouse-derived centromeric chromosome 4 interval (24-45cM)
      surrounding the CD72(b) locus. Unexpectedly, NOD.CD72(b) mice were not protected
      from diabetes, but rather exhibited accelerated development of both insulitis and
      diabetes. Our result defines novel locus or loci in the vicinity of CD72 gene
      that negatively control diabetes, indicating that NOD disease is under complex
      genetic controls of not only Idd genes but also disease-resistant genes.

PMID- 19167350
TI  - Homology-modeled ligand-binding domains of medaka estrogen receptors and androgen
      receptors: a model system for the study of reproduction.
AB  - Estrogen and androgen and their receptors play critical roles in physiological
      processes such as sexual differentiation and development. Using the available
      structural models for the human estrogen receptors alpha and beta and androgen
      receptor as templates, we designed in silico agonist and antagonist models of
      medaka estrogen receptor (meER) alpha, beta-1, and beta-2, and androgen receptor
      (meAR) alpha and beta. Using these models, we studied (1) the structural
      relationship between the ligand-binding domains (LBDs) of ERs and ARs of human
      and medaka, and (2) whether medaka ER and AR can be potential models for studying
      the ligand-binding activities of various agonists and antagonists of these
      receptors by docking analysis. A high level of conservation was observed between
      the sequences of the ligand-binding domains of meERalpha and huERalpha, meERbeta1
      and huERbeta, meERbeta2, and huERbeta with 62.8%, 66.4%, and 65.1% identity,
      respectively. The sequence conservation between meARalpha and huAR, meARbeta, and
      huAR was found with 70.1% and 61.0% of identity, respectively. Thirty-three
      selected endocrine disrupting chemicals (EDCs), including both agonists and
      antagonists, were docked into the LBD of ER and AR, and the corresponding docking
      score for medaka models and human templates were calculated. In order to confirm
      the conservation of the overall geometry and the binding pocket, the backbone
      root mean square deviation (RMSD) for Calpha atoms was derived from the structure
      superposition of all 10 medaka homology models to the six human templates. Our
      results suggested conformational conservation between the ERs and ARs of medaka
      and human, Thus, medaka could be highly useful as a model system for studies
      involving estrogen and androgen interaction with their receptors.

PMID- 19167351
TI  - Fibrinogen facilitates the anti-tumor effect of nonnative endostatin.
AB  - Endostatin is a potent inhibitor of tumor angiogenesis. Interestingly, nonnative
      endostatin also exhibits an anti-tumor effect, which remains a mystery so far.
      Here, we show that intravenous injection of nonnative endostatin results in tumor
      inhibition effect. Soluble and active endostatin is isolated from human blood
      after the addition of nonnative endostatin in vitro. By fractionation of the
      whole blood, we surprisingly identify fibrinogen specifically binding to and
      inhibiting the aggregation of nonnative endostatin. Moreover, the anti-tumor
      activity of nonnative endostatin is substantially impaired in fibrinogen
      deficient mice. Our studies demonstrate that fibrinogen facilitates the anti
      tumor effect of nonnative endostatin, which also provides new insights into the
      novel physiological function of fibrinogen.

PMID- 19167352
TI  - High-throughput quantitative analysis of plant N-glycan using a DNA sequencer.
AB  - High-throughput quantitative analytical method for plant N-glycan has been
      developed. All steps, including peptide N-glycosidase (PNGase) A treatment,
      glycan preparation, and exoglycosidase digestion, were optimized for high
      throughput applications using 96-well format procedures and automatic analysis on
      a DNA sequencer. The glycans of horseradish peroxidase with plant-specific core
      alpha(1,3)-fucose can be distinguished by the comparison of the glycan profiles
      obtained via PNGase A and F treatments. The peaks of the glycans with (91%) and
      without (1.2%) alpha(1,3)-fucose could be readily quantified and shown to harbor
      bisecting beta(1,2)-xylose via simultaneous treatment with alpha(1,3)-mannosidase
      and beta(1,2)-xylosidase. This optimized method was successfully applied to
      analyze N-glycans of plant-expressed recombinant antibody, which was engineered
      to contain a minor amount of glycan harboring beta(1,2)-xylose. These results
      indicate that our DNA sequencer-based method provides quantitative information
      for plant-specific N-glycan analysis in a high-throughput manner, which has not
      previously been achieved by glycan profiling based on mass spectrometry.

PMID- 19167353
TI  - Activation of formyl peptide receptor like-1 by serum amyloid A induces CCL2
      production in human umbilical vein endothelial cells.
AB  - We investigated the effects of serum amyloid A (SAA) on the production of C-C
      chemokine motif ligand 2 (CCL2) and the mechanism underlying SAA action in human
      umbilical vein endothelial cells (HUVECs). Stimulation of HUVECs by SAA elicited
      CCL2 production in a concentration-dependent manner. SAA induced the activations
      of NF-kappaB and AP-1, which were essential for CCL2 production after SAA
      stimulation. HUVECs expressed formyl peptide receptor-like 1 (FPRL1), and short
      interfering RNA knockdown of FPRL1 nearly completely blocked SAA-induced CCL2
      production in HUVECs. We suggest that SAA stimulates CCL2 production via FPRL1
      and, thus, contributes to atherosclerosis.

PMID- 19167354
TI  - Transcriptomic profiling identifies a PU.1 regulatory network in macrophages.
AB  - PU.1 is a key transcription factor for hematopoiesis and macrophage
      differentiation. Using chromatin immunoprecipitation we have previously
      identified several PU.1 target genes in macrophages and microglia. With the aim
      to complement these studies, we performed a transcriptomic analysis of PU.1(-/-)
      progenitors after restoration of PU.1 activity. PUER cells committed to
      macrophage differentiation were analyzed with novel Affymetrix exon 1.0 ST arrays
      and Affymetrix 430 2.0 genome arrays for crosswise validation. We combined these
      genome-wide expression data with a publicly-available microarray dataset of PU.1
      knockdown hematopoietic stem cells for an integrated analysis. Bibliographic gene
      connections, binding site prediction and ChIP-Chip data were used to define a
      multi-level PU.1 regulatory network in macrophages. Moreover, an alternative
      transcript of the novel PU.1 target gene Ptpro was identified by exon arrays and
      PU.1 binding to an intronic promoter was demonstrated. In conclusion, we present
      a PU.1 transcriptional network with novel validated PU.1 target genes.

PMID- 19167355
TI  - Immobilized metal affinity chromatography in the presence of arginine.
AB  - Arginine hydrochloride (ArgHCl) is a versatile solvent additive, as it suppresses
      protein aggregation. ArgHCl has been used for protein refolding and to solubilize
      proteins from loose inclusion bodies. Immobilized metal affinity chromatography
      (IMAC) is one of the most commonly used technologies for purification of
      recombinant proteins. Here we have evaluated compatibility of ArgHCl with IMAC
      purification for his-tag proteins. ArgHCl clearly interfered with protein binding
      to Ni-columns. Nevertheless, such interference was greatly reduced at ArgHCl
      concentration below 200 mM, demonstrating that IMAC purification can be done even
      in the presence of ArgHCl.

PMID- 19167357
TI  - IGF-1 promotes beta-amyloid production by a secretase-independent mechanism.
AB  - Beta-amyloid peptide (Abeta) is generated via the sequential proteolysis of beta
      amyloid precursor protein (APP) by beta- and gamma-secretases, and plays a
      crucial role in the pathogenesis of Alzheimer's disease (AD). Here, we sought to
      clarify the role of insulin-like growth factor-1 (IGF-1), implicated in the AD
      pathomechanism, in the generation of Abeta. Treatment of neuroblastoma SH-SY5Y
      cells expressing AD-associated Swedish mutant APP with IGF-1 did not alter
      cellular levels of APP, but significantly increased those of beta-C-terminal
      fragment (beta-CTF) and secreted Abeta. IGF-1 also enhanced APP phosphorylation
      at Thr668. Treatment of beta-CTF-expressing cells with IGF-1 increased the levels
      of beta-CTF and secreted Abeta. The IGF-1-induced augmentation of beta-CTF was
      observed in the presence of gamma-secretase inhibitors, but not in cells
      expressing beta-CTF with a Thr668 to alanine substitution. These results suggest
      that IGF-1 promotes Abeta production through a secretase-independent mechanism
      involving APP phosphorylation.

PMID- 19167356
TI  - Congenital long QT syndrome caused by the F275S KCNQ1 mutation: mechanism of
      impaired channel function.
AB  - Congenital long QT syndrome is characterized by a prolongation of ventricular
      repolarization and recurrent episodes of life-threatening ventricular
      tachyarrhythmias, often leading to sudden death. We previously identified a
      missense mutation F275S located within the S5 transmembrane domain of the KCNQ1
      ion channel in a Chinese family with long QT syndrome. We used oocyte expression
      of the KCNQ1 polypeptide to study the effects of the F275S mutation on channel
      properties. Expression of the F275 mutant, or co-expression with the wild-type
      S275 polypeptide, significantly decreased channel current amplitudes. Moreover,
      the F275S substitution decreased the rates of channel activation and
      deactivation. In transfected HEK293 cells fluorescence microscopy revealed that
      the F275S mutation perturbed the subcelluar localization of the ion channel.
      These results indicate that the F275S KCNQ1 mutation leads to impaired
      polypeptide trafficking that in turn leads to reduction of channel ion currents
      and altered gating kinetics.

PMID- 19167358
TI  - Ensemble cortical responses to rival visual stimuli: effect of monocular
      transient.
AB  - Binocular rivalry is a fascinating perceptual phenomenon that has been
      characterized extensively at the psychophysical level. However, the underlying
      neural mechanism remains poorly understood. In particular, the role of the early
      visual pathway remains controversial. In this study, we used voltage-sensitive
      dye imaging to measure the spatiotemporal activity patterns in cat area 18 evoked
      by dichoptic orthogonal grating stimuli. We found that after several seconds of
      monocular stimulation with an oriented grating, an orthogonal stimulus to the
      other eye evoked a reversal of the cortical response pattern, which may
      contribute to flash suppression in perception. Furthermore, after several seconds
      of rival binocular stimulation with unequal contrasts, transient increase in the
      contrast of the weak stimulus evoked a long-lasting cortical response. This
      transient-triggered response could contribute to the perceptual switch during
      binocular rivalry. Together, these results point to a significant contribution of
      early visual cortex to transient-triggered switch in perceptual dominance.

PMID- 19167359
TI  - Flavanone exhibits PPARgamma ligand activity and enhances differentiation of 3T3
      L1 adipocytes.
AB  - Flavanones are class of polyphenolic compounds, some of which are found in foods
      and provide health benefits. In this study, we show that flavanone significantly
      enhances differentiation of 3T3-L1 preadipocytes. During adipogenesis, flavanone
      enhanced expression of genes and accumulation of proteins that are involved in
      adipocyte function. Some reports have indicated that flavanone inhibits
      proliferation of mammalian cells, and down-regulates expression of growth-related
      proteins. Such proteins include phosphorylated ERK1/2, cyclins, and Cdks that are
      important for an early event in adipogenesis, mitotic clonal expansion (MCE). We
      demonstrated that flavanone did not inhibit MCE or expression of MCE-related
      proteins, except for a modest inhibition of cyclin D1 expression. Using
      luciferase reporter assays, we found that flavanone acted as a peroxisome
      proliferator-activated receptor gamma (PPARgamma) ligand in a dose-dependent
      manner. Together, our results suggest that flavanone enhances adipogenesis, at
      least in part, through its PPARgamma ligand activity.

PMID- 19167360
TI  - Keap1/Nrf2 system regulates neuronal survival as revealed through study of keap1
      gene-knockout mice.
AB  - Keap1 is proposed to be a sensor protein of electrophilic compounds and a
      transducer of the signal from electrophilic compounds for transcriptional
      activation. Thus, the use of keap1 gene-knockout (KO) mice is a straightforward
      approach in order to clarify the molecular background for the use of
      electrophilies as neuroprotective compounds. In the present report, we
      investigated the question as to how the deletion of the keap1 gene affects the
      activities of Nrf2 and survival of immature cortical neurons. In cortical
      cultures prepared from wild-type (WT) mice, Keap1 was expressed in the neurons,
      and Nrf2 protein was retained in their cytoplasm; whereas Nrf2 was translocated
      into the nuclei of neurons and phase 2 enzymes were constitutively activated in
      the cortical cultures from KO mice. Consistent with these results, cortical
      neurons from KO mice showed increased resistance to oxidative stress induced by
      high concentrations of glutamate and rotenone. These results suggest that the
      absence of Keap1 constitutively activates Nrf2, which then induces the phase 2
      enzymes in neurons and induces increased resistance of cortical neurons to
      oxidative stress. This report is the first report to show that Keap1 is a key
      regulator of cell defense mechanisms of CNS neurons against oxidative stress.

PMID- 19167361
TI  - Flagella-generated forces reveal gear-type motor in single cells of the green
      alga, Chlamydomonas reinhardtii.
AB  - Optically trapped single cells of the biflagellated, green alga, Chlamydomonas
      reinhardtii, rotate. The rotational dynamics of trapped wild-type and mutant
      cells show that functional flagella play a decisive role: the entire flagellar
      apparatus (central microtubules, radial spokes, and dynein arms) is involved. Any
      aberration in this apparatus leads to non-functionality, indicating a gear-type
      mechanism. The translational and rotational motions of the wild-type and mutant
      cells do not differ significantly. Optical forces alone do not play a vital role
      in the rotational dynamics of this cellular motor, making them useful as probes
      of the internal dynamics without external influence.

PMID- 19167362
TI  - Contribution of globular death domains and unstructured linkers to MyD88.IRAK-4
      heterodimer formation: an explanation for the antagonistic activity of MyD88s.
AB  - Homotypic interactions of death domains (DD) mediate complex formation between
      MyD88 and IL-1 receptor-associated kinases (IRAKs). A truncated splice variant of
      MyD88, MyD88s, cannot recruit IRAK-4 and fails to elicit inflammatory responses.
      We have generated recombinant DD of MyD88 and IRAK-4, both alone and extended by
      the linkers to TIR or kinase domains. We show that both MyD88 DD variants bind to
      the linker-extended IRAK-4 DD and pull-down full-length IRAK-4 from monocyte
      extracts. By contrast, residues up to Glu(116) from the DD-kinase connector of
      IRAK-4 are needed for strong interactions with the adaptor. Our findings indicate
      that residues 110-120, which form a C-terminal extra helix in MyD88, but not the
      irregular linker between DD and TIR domains, are required for IRAK-4 recruitment,
      and provide a straightforward explanation for the negative regulation of innate
      immune responses mediated by MyD88s.

PMID- 19167363
TI  - Biosynthesis of an antifungal oligopeptide in Burkholderia contaminans strain
      MS14.
AB  - Strain MS14, exhibiting antifungal activity, was classified to belong to
      Burkholderia contaminans. When compared with the wild type strain, antifungal
      activities of mutants MS14MT13 and MS14MT18 against Geotrichum candidum were
      eliminated, and the activity of mutant MS14MT15 was reduced by approximately 80%.
      Sequence analysis of a 22.7-kb DNA segment revealed the presence of six open
      reading frames (ORFs), including the genes disrupted in the mutants. The wild
      type level of antifungal activity was observed for mutant MS14MT15 (ambR2::Tn5)
      complemented in trans with the intact ambR2 gene, which encodes a LuxR type
      regulator. AmbR2 positively regulates the transcription of the other five ORFs
      identified, which including two nonribosomal peptide synthetase genes required
      for biosynthesis of antifungal compound. The compound consists of amino acid
      residues having a molecular weight of 1200.6 Da. These results show that strain
      MS14 possesses a novel set of genes dedicated to the biosynthesis of an
      antifungal oligopeptide.

PMID- 19167364
TI  - In vitro differentiation of retinal ganglion-like cells from embryonic stem cell
      derived neural progenitors.
AB  - ES cells have been reported to serve as an excellent source for obtaining various
      specialized cell types and could be used in cell replacement therapy. Here, we
      demonstrate the potential of ES cells to differentiate along retinal ganglion
      cell (RGC) lineage. FGF2-induced ES cell derived neural progenitors (ES-NPs) were
      able to generate RGC-like cells in vitro upon differentiation. These cells
      expressed RGC regulators and markers such as, Ath5, Brn3b, RPF-1, Thy-1 and Islet
      1, confirming their potential to differentiate into RGCs. The generation of RGCs
      from ES-NPs was enhanced with the exposure of FGF2 and Sonic hedgehog (Shh),
      although Shh treatment alone did not affect RGC differentiation significantly. ES
      NPs, after exposure to FGF2, were capable of integrating and differentiating into
      RGCs in vivo upon transplantation. Thus, our study suggests that ES cells can
      serve an excellent renewable source for generating RGCs that can be used to treat
      neurodegenerative diseases like glaucoma.

PMID- 19167365
TI  - Related lectins from snowdrop and maize differ in their carbohydrate-binding
      specificity.
AB  - Searches in an EST database from maize revealed the expression of a protein
      related to the Galanthus nivalis (GNA) agglutinin, referred to as GNA(maize).
      Heterologous expression of GNA(maize) in Pichia pastoris allowed characterization
      of the first nucleocytoplasmic GNA homolog from plants. GNA(maize) is a
      tetrameric protein which shares 64% sequence similarity with GNA. Glycan
      microarray analyses revealed important differences in the specificity. Unlike
      GNA, which binds strongly to high-mannose N-glycans, the lectin from maize reacts
      almost exclusively with more complex glycans. Interestingly, GNA(maize) prefers
      complex glycans containing beta1-2 GlcNAc residues. The obvious difference in
      carbohydrate-binding properties is accompanied by a 100-fold reduced anti-HIV
      activity. Although the sequences of GNA and GNA(maize) are clearly related they
      show only 28% sequence identity. Our results indicate that gene divergence within
      the family of GNA-related lectins leads to changes in carbohydrate-binding
      specificity, as shown on N-glycan arrays.

PMID- 19167366
TI  - Non-ATP competitive protein kinase inhibitors as anti-tumor therapeutics.
AB  - Alternative approaches for inhibitor development in targeting sites other than
      the ATP cleft are increasingly being pursued in the search for new therapeutics
      based on inhibition of protein kinases. While recently approved kinase inhibitor
      drugs offer benefit in cancer treatment, further advances are required to affect
      tumor selective cell killing, avoid off-target related toxicities and improve
      survival rates. Protein-protein interactions involved in kinase regulation and
      substrate recognition as well as exploiting allosteric pockets, offer the
      potential for selectivity and avoid decreased efficacy as a result of competition
      with high intracellular ATP concentrations. We discuss several preliminary
      examples where regulatory and substrate binding sites present potential druggable
      interfaces. These include the cell cycle targets which are the cyclin-dependent
      and polo-like kinases among several others.

PMID- 19167367
TI  - Subthalamic nucleus discharge patterns during movement in the normal monkey and
      Parkinsonian patient.
AB  - The pathophysiology of Parkinson disease (PD) is characterized by derangements in
      the discharge rates, bursting patterns, and oscillatory activity of basal ganglia
      (BG) neurons. In this study, subthalamic nucleus (STN) neuronal activity patterns
      in humans with PD were compared with that in the normal monkey during performance
      of similar volitional movements. Single-unit STN recordings were collected while
      PD patients and animals moved a joystick in the direction of targets presented on
      a monitor. When discharge rates in all PD human and normal monkey neurons were
      compared, no significant differences were observed. However, when neurons were
      classified by peri-movement response type (i.e., excited, inhibited, or
      unresponsive to movement) statistical differences were demonstrated - most
      significantly among PD excited neurons. Analysis of burst activity demonstrated
      inter- and intra-burst activities were greater in the PD human compared to the
      monkey irrespective of neuronal response type. Moreover, simultaneously recorded
      neurons in the human demonstrated consistent oscillatory synchronization at
      restricted frequency bands, whereas synchronized oscillatory neurons in the
      monkey were not restricted to distinct frequencies. During movement, discharge
      and burst rates were positively correlated, independent of subject or neuronal
      response type; however, rates and oscillatory activity were more strongly
      correlated in the PD human than the normal monkey. Interestingly, across all
      domains of analysis, STN neurons in PD demonstrated reduced response variability
      when compared to STN neurons in the normal monkey brain. Thus, the net effect of
      PD may be a reduction in the physiological degrees of freedom of BG neurons with
      diminished information carrying capacity.

PMID- 19167368
TI  - Preconditioning with prolonged normobaric hyperoxia induces ischemic tolerance
      partly by upregulation of antioxidant enzymes in rat brain tissue.
AB  - Recent studies suggest that normobaric hyperoxia (HO) results in brain ischemic
      tolerance (BIT), reducing ischemic brain injury. We have attempted to determine
      the time course of HO-induced upregulation of antioxidant enzymes. Rodents
      comprised five groups, breathing room air (RA; O(2)=21%), or 95% oxygen
      (hyperoxia, HO) for 4, 8, 16, and 24 h (RA, 4HO, 8HO, 16HO, 24HO respectively) in
      the same chamber. Each main group was subdivided to MCAO-operated (middle
      cerebral artery occlusion), and intact (without any surgery) subgroups. After 24
      h, MCAO-operated subgroups were subjected to 60 min of right MCAO. After 24 h
      reperfusion, neurologic deficit score (NDS), mortality rate, and infarct volume
      were measured in MCAO-operated subgroups. 48 h after pretreatment, antioxidant
      enzymes activities were assessed in MCAO-operated, sham-operated, and intact
      subgroups. Preconditioning with 16HO and 24HO decreased NDS, mortality rate,
      infarct volume, and increased antioxidant enzymes activities (superoxide
      dismutase, catalase, glutathione peroxidase, and glutathione reductase)
      significantly. Although further studies are needed to clarify the mechanisms of
      ischemic tolerance, the prolonged HO seems to partly exert their effects via
      increase in antioxidant enzymes activities.

PMID- 19167369
TI  - Inhibition of U-87 human glioblastoma cell proliferation and formyl peptide
      receptor function by oligomer procyanidins (F2) isolated from grape seeds.
AB  - Gliomas are the most common and lethal tumor type in the brain. The present study
      investigated the effect of oligomer procyanidins (F2) (F2, degree of
      polymerization 2-15), a natural fraction isolated from grape seeds on the
      biological behavior of glioblastoma cells. We found that F2 significantly
      inhibited the glioblastoma growth, with little cytotoxicity on normal cells,
      induced G2/M arrest and decreased mitochondrial membrane potential in U-87 cells.
      It also induced a non-apoptotic cell death phenotype resembling paraptosis in U
      87 cells. In addition, it was found for the first time that F2 in non-cytotoxic
      concentrations selectively inhibited U-87 cell chemotaxis mediated by a G-protein
      coupled receptor formyl peptide receptor FPR, which is implicated in tumor cell
      invasion and metastasis. Further experiments indicated that F2 inhibited fMLF
      induced U-87 cell calcium mobilization and MAP kinases ERK1/2 phosphorylation.
      Moreover, F2 attenuated the glioblastoma FPR expression, a new molecular target
      for glioma therapeutics, which has been shown to play important roles in glioma
      cells chemotaxis, proliferation and angiogenesis in addition to its promotion to
      tumor progression, but did not affect FPR mRNA expression in U-87 cells. Taken
      together, our results suggest that F2 may be a promising candidate for the
      development of novel anti-tumor therapeutics.

PMID- 19167370
TI  - Structure-function roles of four cysteine residues in the human arsenic (+3
      oxidation state) methyltransferase (hAS3MT) by site-directed mutagenesis.
AB  - Cysteine (Cys) residues are often crucial to the function and structure of
      proteins. Cys157 and Cys207 in recombinant mouse arsenic (+3 oxidation state)
      methyltransferase (AS3MT) are shown to be related to enzyme activity and
      considered to be the catalytic sites. The roles of some conserved Cys residues in
      the N-terminal region of the rat AS3MT also have been examined. However, little
      is known about the roles of the Cys residues in the middle region. The metabolism
      of inorganic arsenic in human is different from rat and mouse in some aspects
      though the AS3MT has a high degree of similarity in these species. In order to
      determine whether the Cys156 and Cys206 (corresponding to the catalytic sites,
      Cys157 and Cys207 in the mouse AS3MT) in the hAS3MT act as the catalytic sites
      and to study the roles of the Cys residues (Cys226 and Cys250) near the catalytic
      center in the middle region, we designed and prepared four mutants (C156S, C206S,
      C226S, and C250S) in which one Cys residue replaced by serine by PCR-based site
      directed mutagenesis. The native form and cysteine/serine mutants were assayed
      for enzyme activity, free thiols, and the secondary structures by circular
      dichroism and Fourier transform infrared. Our data show that, besides C156S and
      C206S, C250S is another potential important site. C226S seems to have the same
      action as the wild-type hAS3MT with the consistent K(M) and V(max) values.
      Meanwhile, selenium can also inhibit the methylation of inorganic arsenic by
      C226S. All the mutants except C226S are calculated to have dramatic changes in
      the secondary structures. Cys250 might form an intramolecular disulfide bond with
      another Cys residue. These findings demonstrate that Cys residues at positions
      156, 206, and 250 play important roles in the enzymatic function and structure of
      the hAS3MT.

PMID- 19167371
TI  - Association between EGF and lipid concentrations: a benefit role in the
      atherosclerotic process?
AB  - CONTEXT AND OBJECTIVE: Previous in vitro studies have shown a relationship
      between epidermal growth factor (EGF) and lipid metabolism. Indeed, EGF is able
      to modulate lipoprotein fractions in human fetal intestine and hepatic-derived
      cell lines. The aim of this study was to search for potential associations
      between EGF concentrations and lipid parameters in both plasma and peripheral
      blood mononuclear cells (PBMCs) among healthy individuals. DESIGN: EGF
      concentrations were quantified in plasma of 273 men and 279 women and in PBMCs of
      57 men and 62 women from the STANISLAS cohort. In addition, basic blood
      constituents including lipid parameters (apolipoproteins A1, and B, total and
      high-density lipid (HDL)-cholesterols and triglycerides) were measured. RESULTS:
      Plasma EGF concentrations were significantly and positively correlated with
      apolipoprotein A1 and HDL-cholesterol concentrations after adjustment for age,
      sex, and body mass index (r=0.155, P=0.0003; and r=0.112, P=0.0086,
      respectively). They were also negatively correlated with the apolipoprotein B/A1
      ratio (r=-0.107, P=0.012). In addition, EGF concentrations in PBMCs were
      negatively correlated with apolipoprotein B, total and low-density lipid
      cholesterols, and triglyceride concentrations, and apolipoprotein B/A1 ratio
      (P=0.0018, P=0.0137, P=0.0142, P=0.0162, and P=0.0077, respectively, with r
      ranging between -0.287 and -0.222). No interactions were found with gender.
      CONCLUSION: New associations between EGF and lipid concentrations have been
      reported, providing new perspectives with regard to the role of EGF in
      atherosclerosis.

PMID- 19167372
TI  - Clinical and molecular aspects of Berardinelli-Seip Congenital Lipodystrophy
      (BSCL).
AB  - Congenital Generalized Lipodystrophy (CGL) or Berardinelli-Seip Syndrome (BSCL)
      is a rare autosomal recessive disease characterized by complete absence of
      adipose tissue and by several metabolic alterations in carbohydrate (diabetes
      mellitus) and lipid metabolism and involvement of heart, bone and ovaries. Mental
      retardation and psychiatric disturbances are present in a variable proportion of
      affected patients. In the present review, the major advances in clinical,
      molecular and genetic characterization of BSCL affected subjects are recorded and
      discussed.

PMID- 19167373
TI  - The macrophage migration inhibitory factor (MIF) gene polymorphism in Czech and
      Russian patients with myocardial infarction.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine implicated
      in early and advanced atherosclerosis. The aim of this study was to investigate
      whether polymorphism of MIF gene is associated with myocardial infarction (MI).
      METHODS: Single nucleotide polymorphism (SNP) in MIF gene (-173G/C, rs755622) was
      investigated in Czech (n=219) and Russian (n=240) MI patients and population
      control from the same geographical areas (Czech, n=137; Russian, n=174). Further,
      another SNP (rs1007888) located within the 3' flanking region of the MIF gene was
      investigated in Czech MI patients and control subjects. RESULTS: There were no
      significant differences in the distribution of MIF -173G/C genotypes, alleles or
      carriage rates between case and control groups in either populations. However,
      the GG genotype of the MIF SNP rs1007888 was associated with MI in Czech female
      patients (p=0.027). CONCLUSIONS: Taken together with previous reports, our study
      suggests that particular MIF gene polymorphisms may contribute to MI
      susceptibility in females.

PMID- 19167374
TI  - Overview on self-monitoring of blood glucose.
AB  - The self-monitoring of blood glucose (SMBG), traditionally performed by "point-of
      care" (POC) devices called portable glucose monitors (PGM) is now considered an
      integral part of managed care of diabetic patients, especially type 1 diabetics
      and those on insulin therapy. In patients with type 2 diabetes, SMBG can help to
      achieve a better glycaemic control, although there is not sufficient evidence to
      attest that strict monitoring in these patients is associated with an improved
      outcome. The outcome of several clinical studies, especially in diabetics on
      insulin therapy, has shown that SMBG plays a key role in preventing complications
      in the short, medium and long term. According to the current recommendations,
      SMBG is aimed to achieve and maintain glycaemic control, prevent and identify
      hypoglycaemia, prevent severe hyperglycaemia, adjust lifestyle changes and
      establish the need to begin treatment with insulin in gestational diabetes
      mellitus. However, as clearly highlighted by the American Diabetes Association
      (ADA) and the National Academy of Clinical Biochemistry (NACB), patients and
      healthcare personnel should be trained on the appropriate use of the device, as
      well as on the correct interpretation of data. Moreover, definite analytical
      targets and appropriate acceptance criteria for performance should be fulfilled
      before a new device is introduced in the hospital environment, or recommended to
      the patients. Performance limitations such as hematocrit extremes and analytical
      interferences should be clearly acknowledged by the operators, before taking test
      results for granted. The current article aims to review the current indications
      for SMGB and highlight the most important criteria for the appropriate use of
      PGMs.

PMID- 19167375
TI  - DANCE/fibulin-5 promotes elastic fiber formation in a tropoelastin isoform
      dependent manner.
AB  - OBJECTIVE: To investigate a function of fibulin-5 in the elastic fiber formation,
      we studied the molecular interactions among elastin, fibrillin-1, and fibulin-5
      in the extracellular space and the maturation of tropoelastin using retinal
      pigment epithelial cells (ARPE-19). DESIGN AND METHODS: Bacterial recombinant
      tropoelastin (rTE) was added to ARPE-19 cells overexpressing V5-tagged fibulin-5
      (ARPE-Fibulin-5). These elastic fibers were evaluated by immunofluorescence
      staining, the quantitative analysis of cross-linked amino acids, and semi
      quantitative analysis of matrix-associated tropoelastin. RESULTS:
      Immunoprecipitation assays revealed that fibulin-5 is able to separately interact
      with tropoelastin or fibrillin-1 in the culture medium. Moreover,
      immunofluorescent staining showed that elastin, fibrillin-1, and fibulin-5 co
      localize in the extracellular matrix. Desmosine levels were significantly
      increased in ARPE-Fibulin-5 relative to untransfected cells in spite of equal
      deposition of tropoelastin by enzyme-linked immunosorbent assay. The addition of
      a tropoelastin isoform, which lacked the peptide encoded by exon 26A (Delta26A)
      and could bind to fibulin-5 strongly, led to a larger increase in cross-linking
      amino acids compared to tropoelastin containing the exon 26A peptide sequence.
      CONCLUSION: These data provide new insights into the initial steps of elastic
      fiber assembly and identify fibulin-5 and tropoelastin isoforms as potential
      targets for the regeneration of elastic fibers in vivo.

PMID- 19167376
TI  - Proteomic analysis of normal human nasal mucosa: establishment of a two
      dimensional electrophoresis reference map.
AB  - OBJECTIVE: To construct a partial two-dimensional electrophoresis (2-DE)
      reference map of the proteins that compose normal human nasal mucosa. DESIGN AND
      METHODS: Normal inferior turbinate mucosa samples were subjected to 2-DE, the
      protein spots were visualized by silver staining, and 78 spots were selected for
      analysis by mass spectrometry and bioinformatics. Reverse transcriptase
      polymerase chain reaction (RT-PCR) and immunohistochemical techniques were
      performed for validation and localization analysis. RESULTS: Among the identified
      proteins, the largest functional groups included proteins associated with the
      human immune response and enzymes, particularly those of protein metabolism.
      Proteins participating in the cell cycle, cell division, calcium metabolism, and
      ion transport were also detected. The mRNA transcripts for 10 selected proteins
      were amplified by RT-PCR. Immunohistochemistry revealed that secretagogin was
      localized in the submucosal gland and calsenilin was localized in the epithelium
      and submucosal gland. CONCLUSION: This database will serve as the basis for
      further comparative proteomic studies of nasal mucosal disorders.

PMID- 19167377
TI  - Involvement of an inner nuclear membrane protein, Nemp1, in Xenopus neural
      development through an interaction with the chromatin protein BAF.
AB  - To clarify the molecular mechanisms of neural development in vertebrates, we
      analyzed a novel gene, termed nemp1 (nuclear envelope integral membrane protein
      1), which is expressed in the Xenopus anterior neuroectoderm at the neurula
      stage. Nemp1 has a putative signal peptide and five transmembrane domains, but
      does not have any other known domains. We show that Nemp1 is localized to the
      inner nuclear membrane (INM) with its evolutionarily conserved C-terminal region
      facing the nucleoplasm. Both overexpression and knockdown of Nemp1 in Xenopus
      embryos reduced the expression of early eye marker genes, rax, tbx3, and pax6,
      and later resulted mainly in severe eye defects at the tailbud stage. In
      contrast, the expression of a forebrain/midbrain marker, otx2, and a pan-neural
      marker, sox2, was largely unaffected. Deletion analysis of Nemp1 showed that
      nuclear envelope-localization of the C-terminal region is necessary for its eye
      reducing activity. Furthermore, nemp1 is coexpressed with baf (barrier-to
      autointegration factor) in the eye anlagen, and that Nemp1 interacts with BAF
      through the BAF-binding site in the C-terminal region and this site is required
      for Nemp1 activity. These data suggest that Nemp1 is involved in the expression
      of eye marker genes by functioning at the INM at least partly through BAF.

PMID- 19167378
TI  - Role of CD44s and CD44v6 on human breast cancer cell adhesion, migration, and
      invasion.
AB  - The interaction between the transmembrane receptor CD44 on epithelial tumor cells
      and its ligand hyaluronan in the surrounding extracellular matrix is important in
      tumor progression and metastasis. CD44 is encoded by a single 20-exon gene and
      expressed in standard form (CD44s), as well as a myriad of CD44 variants (CD44v)
      generated by alternative splicing of the CD44 mRNA. Previously, we demonstrated
      that hyaluronan (HA) production is increased at tumor-stroma interface in
      invasive and metastatic human breast cancers when compared with benign or
      premalignant lesions. We hypothesize that CD44 expression on breast cancer cells
      is a major contributing factor to cell adhesion, migration and invasion. To
      evaluate this hypothesis we examined the effects of 3 distinct anti-CD44s and 2
      anti-CD44v6 monoclonal antibodies on breast cancer cell lines that expressed high
      and low CD44s and CD44v6. Using these antibodies we assessed the role of CD44 in
      cell adhesion, cell motility, and cell invasion using immobilized HA-coated
      wells, wound healing assays, and modified Boyden chamber respectively. Our
      results showed that anti-CD44s could inhibit breast cancer cell adhesion,
      motility and invasion, while anti-CD44v6 inhibits cell motility. In conclusion,
      our data suggests that CD44s is involved in breast cancer cell adhesion, motility
      and invasion through interaction with HA but CD44v6 is involved only in cell
      motility. Furthermore we concluded that antibodies against different epitopes on
      CD44 mediate distinct functional effects on breast cancer cells.

PMID- 19167379
TI  - Vascular wall resident progenitor cells: a review.
AB  - The vessel wall has usually been thought to be relatively quiescent. But the
      discovery of progenitor cells in many tissues and in the vasculature itself has
      led to a reconsideration of the vascular biology. The presence of circulating
      endothelial and smooth muscle progenitors able to home to the injured vascular
      wall is a firm acquisition; less known is the notion, coming from embryonic and
      adult tissue studies, that stem cells able to differentiate into endothelial
      cells and smooth muscle cells also reside in the arterial wall. Moreover, the
      existence of a vasculogenic zone has recently been identified in adult human
      arteries; this niche-like zone is believed to act as a source of progenitors for
      postnatal vasculogenesis. From the literature it is already apparent that a
      complex interplay between circulating and resident vascular wall progenitors
      takes place during embryonal and postnatal life; a structural/functional disarray
      of these intimate stem cell compartments could hamper appropriate vascular
      repair, the development of vascular wall disease being the direct clinical
      consequence in adult life. This review gives an overview of adult large vessel
      progenitors established in the vascular wall during embryogenesis and their role
      in the maintenance of wall homeostasis.

PMID- 19167380
TI  - The activation of human endogenous retrovirus K (HERV-K) is implicated in
      melanoma cell malignant transformation.
AB  - Melanoma development is a multi-step process arising from a series of genetic and
      epigenetic events. Although the sequential stages involved in progression from
      melanocytes to malignant melanoma are clearly defined, our current understanding
      of the mechanisms leading to melanoma onset is still incomplete. Growing evidence
      show that the activation of endogenous retroviral sequences might be involved in
      transformation of melanocytes as well as in the increased ability of melanoma
      cells to escape immune surveillance. Here we show that human melanoma cells in
      vitro undergo a transition from adherent to a more malignant, non-adherent
      phenotype when exposed to stress conditions. Melanoma-derived non-adherent cells
      are characterized by an increased proliferative potential and a decreased
      expression of both HLA class I molecules and Melan-A/MART-1 antigen, similarly to
      highly malignant cells. These phenotypic and functional modifications are
      accompanied by the activation of human endogenous retrovirus K expression (HERV
      K) and massive production of viral-like particles. Down-regulation of HERV-K
      expression by RNA interference prevents the transition from the adherent to the
      non-adherent growth phenotype in low serum. These results implicate HERV-K in at
      least some critical steps of melanoma progression.

PMID- 19167381
TI  - Lack of digalactosyldiacylglycerol increases the sensitivity of Synechocystis sp.
      PCC 6803 to high light stress.
AB  - The physiological role of digalactosyldiacylglycerol (DGDG) in photosynthesis was
      examined using a dgdA mutant of Synechocystis sp. PCC 6803 that is defective in
      the biosynthesis of DGDG. The dgdA mutant cells showed normal growth under low
      light (LL) conditions. However, their growth was retarded under high light (HL)
      conditions and under Ca(2+)- and/or Cl(-)-limited conditions compared to wild
      type cells. The retardation in growth of the mutant cells was recovered by
      exogenous supply of DGDG in the growth medium. The dgdA mutant showed increased
      sensitivity to photoinhibition. Although both photodamage and repair processes of
      photosynthesis were affected, the repair process was more severely affected than
      the photodamage process, suggesting that DGDG plays an important role in the
      photosynthetic repair cycle.

PMID- 19167382
TI  - Expression analysis of phytohormone-regulated microRNAs in rice, implying their
      regulation roles in plant hormone signaling.
AB  - Twenty-two conserved miRNAs were chosen to investigate the expression pattern in
      response to phytohormone treatments, in which the effects of five classic plant
      hormone stresses were surveyed in Oryza sativa. The results showed that 11 miRNAs
      were found to be dysregulated by one or more phytohormone treatments. The target
      genes of these miRNAs were validated in vivo and their expression profiling were
      revealed. We also analyzed the promoter regions of the 22 conserved miRNAs for
      phytohormone-responsive elements and the existence of the elements provided
      further evidences supporting our results. These findings enable us to further
      investigate the role of miRNAs in phytohormone signaling.

PMID- 19167383
TI  - Sphingolipids and membrane environments for caveolin.
AB  - Caveolin-1, and probably also -2 and -3, can organize multimolecular membrane
      complexes involved in transmembrane traffic, cell adhesion and signal
      transduction. In this review, we discuss on the importance of caveolin membrane
      environment in regulating the architecture and function of such complexes, with a
      special emphasis on the role of sphingolipids.

PMID- 19167384
TI  - Electronic clinical challenges and images in GI. Giant gastric polyp prolapsing
      into the duodenum.

PMID- 19167388
TI  - Clinical challenges and images in GI. Peutz-Jeghers syndrome with gastroduodenal
      intussusception secondary to gastric cancer.

PMID- 19167389
TI  - Advanced neoplasia detection rates at colonoscopy screening: implications for CT
      colonography.

PMID- 19167391
TI  - Bak to basics of colonocyte renewal.

PMID- 19167393
TI  - Clinical challenges and images in GI. Endoscopic ultrasound trucut needle biopsy
      of a rare pancreatic lesion.

PMID- 19167395
TI  - Nitazoxanide: beyond parasites toward a novel agent for hepatitis C.

PMID- 19167396
TI  - Does MicroRNA microarray for the microsatellite status have a big translational
      impact?

PMID- 19167397
TI  - Adenosine triphosphate energizes intestinal T(H)17 cells.

PMID- 19167398
TI  - Role of RHO kinase in gastrointestinal motility.

PMID- 19167399
TI  - Cell transplantation to replace whole liver transplantation.

PMID- 19167400
TI  - Glucose-dependent and -independent electrical activity in islets of Langerhans of
      Psammomys obesus, an animal model of nutritionally induced obesity and diabetes.
AB  - Glucose-induced insulin secretion from pancreatic beta-cells involves metabolism
      induced membrane depolarization and voltage-dependent Ca(2+) influx. The
      electrical events in beta-cell glucose sensing have been studied intensely using
      mouse islets of Langerhans, but data from other species, including models of type
      2 diabetes mellitus (T2DM), are lacking. In this work, we made intracellular
      recordings of electrical activity from cells within islets of the gerbil
      Psammomys obesus (fat sand rat), a model of dietary-induced T2DM. Most islet
      cells from lean, non-diabetic sand rats displayed glucose-induced, K(ATP) channel
      dependent, oscillatory electrical activity that was similar to the classic
      "bursting" pattern of mouse beta-cells. However, the oscillations were slower in
      sand rat islets, and the dose-response curve of electrical activity versus
      glucose concentration was left-shifted. Of the non-bursting cells, some produced
      action potentials continuously, while others displayed electrical activity that
      was largely independent of glucose. The latter activity consisted of continuous
      or intermittent action potential firing, and persisted for long periods in the
      absence of glucose. The glucose-insensitive activity was suppressed by diazoxide,
      indicating that the cells expressed K(ATP) channels. Sand rat islets produced
      intracellular Ca(2+) oscillations reminiscent of the oscillatory electrical
      pattern observed in most cells, albeit with a longer period. Finally, we found
      that the glucose dependence of insulin secretion from sand rat islets closely
      paralleled that of the bursting electrical activity. We conclude that while
      subpopulations of K(ATP)-expressing cells in sand rat islets display
      heterogeneous electrical responses to glucose, insulin secretion most closely
      follows the oscillatory activity. The ease of recording membrane potential from
      sand rat islets makes this a useful model for studies of beta-cell electrical
      signaling during the development of T2DM.

PMID- 19167401
TI  - UV protectants for the biopesticide based on Bacillus sphaericus Neide and their
      role in protecting the binary toxins from UV radiation.
AB  - The UV protectant properties of 26 natural and synthetic compounds were
      investigated for a biopesticide based on an indigenously isolated strain (ISPC-8)
      of Bacillus sphaericus Neide. In initial screening, spores of ISPC-8 with 0.1%
      (w/w for solid and v/w for liquid materials) concentration of different compounds
      were exposed to UV-B radiation (4.9 x 10(5) J/m(2)) for 6h and their spore
      viability and larvicidal activity were studied. The larvicidal activity was
      evaluated against third-instar larvae of Culex quinquefasciatus Say. There was a
      complete loss of spore viability (1.4% viable spores) and partial reduction in
      larvicidal activity (57.7% of original activity) after exposure of spores to UV-B
      for 6h. However, spore viability as well as larvicidal activity protected
      significantly when spores were mixed with different compounds before exposing
      them to UV-B. Among the different compounds tested benzaldehyde, congo red, para
      aminobenzoic acid (PABA) and cinnamaldehyde were found to be promising in
      protecting the spores from UV-B radiation. The presence of binary toxins (41.9
      kDa and 51.4 kDa) in protected and unprotected samples were examined by SDS-PAGE.
      The binary toxin bands disappeared in unprotected spores after 24h of exposure to
      UV-B, whereas toxin bands were distinctly visible when spores with benzaldehyde
      and cinnamaldehyde were exposed to UV-B for 96 h and 120 h, respectively. Congo
      red and PABA were found to be most effective in protecting binary toxins even
      after 168 h of exposure to UV-B. Incorporation of these promising UV protectant
      compounds in biopesticides would help in protecting the spores from the adverse
      effects of UV radiation and prolong the persistence of biopesticides under field
      conditions.

PMID- 19167402
TI  - Platelet derived serotonin drives the activation of rat cardiac fibroblasts by 5
      HT2A receptors.
AB  - Platelet activation occurs in different acute and chronic heart diseases
      including myocardial infarction, obstructive hypertrophic cardiomyopathy and
      valve stenosis. Recent studies suggested that some factors secreted by activated
      platelets may participate in cardiac remodeling. In the present study, we
      investigated whether platelets and platelet-released serotonin (5-HT) are
      directly involved in the functional regulation of cardiac fibroblasts. Treatment
      of neonatal rat cardiac fibroblasts with platelet lysate, 5-HT and the 5-HT2A
      receptor agonist DOI increased the expression of alpha-SMA protein, a marker of
      fibroblast differentiation into myofibroblasts. Platelet lysate, 5-HT and DOI
      also induced a time-dependent stimulation of cardiac fibroblast migration that
      was inhibited by the 5-HT2A receptor antagonist ketanserin. Finally, incubation
      of cardiac fibroblasts with platelet lysate or 5-HT enhanced secretion of TGF
      beta1 and expression of MMP-3 and MMP-13. As observed for fibroblast migration,
      these effects were prevented by ketanserin. These results demonstrated for the
      first time that factors released from platelet directly regulate cardiac
      fibroblasts by enhancing secretion of TGF-beta1 and MMPs and promoting their
      migration and differentiation. 5-HT released by platelets appears to be a major
      contributor of platelet effects which are mediated through 5-HT2A receptors.

PMID- 19167404
TI  - Solution structure of human zeta-COP: direct evidences for structural similarity
      between COP I and clathrin-adaptor coats.
AB  - COP-I-coated vesicles are protein and lipid carriers that mediate intra-Golgi
      transport and transport from the cis-Golgi complex to the endoplasmic reticulum
      in cells. The coatomer of the vesicles coat is comprised of seven subunits: alpha
      COP, epsilon-COP, beta'-COP, beta-COP, gamma-COP, delta-COP, and zeta-COP. Here
      we report the solution structure of a truncated form (residues 1-149; zeta
      COP149) of human zeta-COP (total 177 residues). It is the first three-dimensional
      structure of a "core" subunit of the COP I F-subcomplex. The structure of zeta
      COP149 mainly consists of a disordered N-terminal tail, a five-stranded
      antiparallel beta-sheet, a two-stranded antiparallel beta-sheet, and five alpha
      helices. The global folding of zeta-COP149 is very similar to the crystal
      structures of AP1-sigma1 and AP2-sigma2, directly demonstrating the structural
      similarity between the "core" subunits of the COP I F-subcomplex and adaptor
      protein complexes. Through structural comparison and mutagenesis study, we have
      also demonstrated that the heterodimers of zeta-COP149 and gamma-COP have packing
      interfaces and relative subunit orientations similar to those of AP2-sigma2 and
      AP2-alpha heterodimers. These results provide direct evidence supporting the
      previous proposal that the COP I F-subcomplex and adaptor protein complexes have
      similar tertiary and quaternary structures.

PMID- 19167403
TI  - Structural basis for catalysis of a tetrameric class IIa fructose 1,6
      bisphosphate aldolase from Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), currently
      infects one-third of the world's population in its latent form. The emergence of
      multidrug-resistant and extensive drug-resistant strains has highlighted the need
      for new pharmacological targets within M. tuberculosis. The class IIa fructose
      1,6-bisphosphate aldolase (FBA) enzyme from M. tuberculosis (MtFBA) has been
      proposed as one such target since it is upregulated in latent TB. Since the
      structure of MtFBA has not been determined and there is little information
      available on its reaction mechanism, we sought to determine the X-ray structure
      of MtFBA in complex with its substrates. By lowering the pH of the enzyme in the
      crystalline state, we were able to determine a series of high-resolution X-ray
      structures of MtFBA bound to dihydroxyacetone phosphate, glyceraldehyde 3
      phosphate, and fructose 1,6-bisphosphate at 1.5, 2.1, and 1.3 A, respectively.
      Through these structures, it was discovered that MtFBA belongs to a novel
      tetrameric class of type IIa FBAs. The molecular details at the interface of the
      tetramer revealed important information for better predictability of the
      quaternary structures among the FBAs based on their primary sequences. These X
      ray structures also provide interesting and new details on the reaction mechanism
      of class II FBAs. Substrates and products were observed in geometries poised for
      catalysis; in addition, unexpectedly, the hydroxyl-enolate intermediate of
      dihydroxyacetone phosphate was also captured and resolved structurally. These
      concise new details offer a better understanding of the reaction mechanisms for
      FBAs in general and provide a structural basis for inhibitor design efforts aimed
      at this class of enzymes.

PMID- 19167405
TI  - Spatial spreading of West Nile Virus described by traveling waves.
AB  - In this work, we propose a spatial model to analyze the West Nile Virus
      propagation across the USA, from east to west. West Nile Virus is an arthropod
      borne flavivirus that appeared for the first time in New York City in the summer
      of 1999 and then spread prolifically among birds. Mammals, such as humans and
      horses, do not develop sufficiently high bloodstream titers to play a significant
      role in the transmission, which is the reason to consider the mosquito-bird
      cycle. The model aims to study this propagation based on a system of partial
      differential reaction-diffusion equations taking the mosquito and the avian
      populations into account. Diffusion and advection movements are allowed for both
      populations, being greater in the avian than in the mosquito population. The
      traveling wave solutions of the model are studied to determine the speed of
      disease dissemination. This wave speed is obtained as a function of the model's
      parameters, in order to assess the control strategies. The propagation of West
      Nile Virus from New York City to California state is established as a consequence
      of the diffusion and advection movements of birds. Mosquito movements do not play
      an important role in the disease dissemination, while bird advection becomes an
      important factor for lower mosquito biting rates.

PMID- 19167406
TI  - Renal dopaminergic system activity in rat remnant kidney up to twenty-six weeks
      after surgery.
AB  - AIMS: In 3/4 nephrectomized (3/4nx) rats the renal dopaminergic system was
      suggested to be involved in the adaptive increase of sodium excretion two weeks
      after renal mass ablation. The aim of the present study was to evaluate the renal
      adaptations in sodium handling and renal dopaminergic system activity in 3/4nx
      rats up to twenty-six weeks after surgery. MAIN METHODS: The rats were placed in
      metabolic cages for the collection of 24 h urine for evaluation of sodium,
      dopamine, dopamine precursor and metabolites. Blood pressure, aromatic L-amino
      acid decarboxylase (AADC) activity in proximal tubules and the effect of dopamine
      D(1) receptor selective antagonist (Sch-23390) on natriuresis was evaluated. KEY
      FINDINGS: A time-dependent increase in both systolic and diastolic blood pressure
      was observed in 3/4nx rats, and this was accompanied by a decrease in urinary
      levels of dopamine and in renal AADC activity at twenty-six weeks after renal
      mass ablation. In contrast to what has been found two weeks after renal mass
      ablation, the natriuretic response to volume expansion was progressively reduced
      in 3/4nx rats at ten and twenty-six weeks after surgery and this was accompanied
      by insensitivity of natriuresis to Sch-23390. SIGNIFICANCE: In conclusion the
      renal dopaminergic system activity is compromised in 3/4nx rats in a time
      dependent manner after renal mass ablation. It is suggested that this may
      contribute to compromise sodium excretion and increase blood pressure, in chronic
      renal insufficiency.

PMID- 19167407
TI  - Antioxidant effect of a novel class of telluroacetilene compounds: studies in
      vitro and in vivo.
AB  - AIMS: The effect of telluroacetylenes a-d on pharmacological assays was
      investigated in vitro. A second objective of this study was to investigate the
      antioxidant action of compound b against the oxidative damage induced by sodium
      nitroprusside (SNP) in mouse brain. MAIN METHODS: In in vitro experiments, lipid
      peroxidation (LP) and protein carbonyl (PC) levels and delta-aminolevulinate
      dehydratase (delta-ALA-D) activity were carried out in rat brain homogenate. The
      thiol peroxidase-like activity and DPPH radical scavenging of telluroacetylenes a
      d were investigated. In in vivo experiments, mice received SNP (0.335 micromol
      per site) intra cerebroventricular (i.c.v.) thirty minutes after oral
      administration of telluroacetylene b (10 mg/kg). After 1 h, animals were
      euthanized. The levels of LP and delta-ALA-D, catalase (CAT), glutathione
      peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST)
      activities were carried out in mouse brain homogenate. KEY FINDINGS:
      Telluroacetylenes a-d, at low muM range, reduced LP and PC levels in rat brain
      homogenate. Telluroacetylenes a-d showed effect of scavenging DPPH radicals.
      delta-ALA-D activity was inhibited by telloruacetylenes a-d, at high muM range,
      in rat brain homogenate. Brains of mice treated with SNP showed an increase in LP
      and the reduction in delta-ALA-D, GR and GST activities. Telluroacetylene b
      protected against the oxidative stress caused by SNP in brain of rats.
      SIGNIFICANCE: The results support an antioxidant effect of telluroacetylenes a-d
      in vitro. Telluroacetylene b protected against oxidative damage caused by SNP in
      mouse brain, suggesting an antioxidant effect of this compound.

PMID- 19167408
TI  - Enhanced activity of very low density lipoprotein receptor II promotes SGC7901
      cell proliferation and migration.
AB  - AIMS: Clear differences of biological function between very low density
      lipoprotein receptor (VLDLR) types I and II have not been defined. The purpose of
      this study is to characterize VLDLR activities during cell proliferation and
      migration using adenocarcinoma SGC7901 cells. MAIN METHODS: Western blotting was
      used to test protein expression. Cell proliferation or migration was analyzed by
      MTT or Transwell chambers respectively. The mRNA expression was tested by RT-PCR.
      Reporter assay was to test the transcription activity. KEY FINDINGS: The cells
      treated with all-trans retinoic acid (ATRA) became well differentiated and had a
      gradually attenuated cell proliferation and migration, accompanied by a
      significant decrease in type II VLDLR expression. These cells also had decreased
      amount of beta-catenin, indicating a decreased stability of beta-catenin. In
      addition, the mRNA expression of both matrix metalloproteinase (MMP)-2 and MMP-9
      was also decreased. On the contrary, cells treated with phorbol-12-myristate-13
      acetate (PMA) had an increase in type II VLDLR expression, whereas the beta
      catenin was increased. This was accompanied by increased cell proliferation and
      migration and by increased MMP-2 and MMP-9 mRNA expression. Finally, the
      transfection of SGC7901 cells with type II VLDLR recombinant DNA induced the cell
      proliferation and migration as well as the activation of beta-catenin/T cell
      factor (TCF) signaling. However, type I VLDLR transfection reduced beta-catenin
      stability and decreased cell proliferation and migration. SIGNIFICANCE: These
      data strongly suggest that type II VLDLR activity is positively associated with
      significant change of tumor cell proliferation and migration, via the beta
      catenin/TCF signaling.

PMID- 19167409
TI  - Differential modulation of late sodium current by protein kinase A in R1623Q
      mutant of LQT3.
AB  - AIMS: In the type 3 long QT syndrome (LQT3), shortening of the QT interval by
      overdrive pacing is used to prevent life-threatening arrhythmias. However, it is
      unclear whether accelerated heart rate induced by beta-adrenergic agents produces
      similar effects on the late sodium current (I(Na)) to those by overdrive pacing
      therapy. We analyzed the beta-adrenergic-like effects of protein kinase A and
      fluoride on I(Na) in R1623Q mutant channels. MAIN METHODS: cDNA encoding either
      wild-type (WT) or R1623Q mutant of hNa(v)1.5 was stably transfected into HEK293
      cells. I(Na) was recorded using a whole-cell patch-clamp technique at 23 degrees
      C. KEY FINDINGS: In R1623Q channels, 2 mM pCPT-AMP and 120 mM fluoride
      significantly delayed macroscopic current decay and increased relative amplitude
      of the late I(Na) in a time-dependent manner. Modulations of peak I(Na) gating
      kinetics (activation, inactivation, recovery from inactivation) by fluoride were
      similar in WT and R1623Q channels. The effects of fluoride were almost completely
      abolished by concomitant dialysis with a protein kinase inhibitor. We also
      compared the effect of pacing with that of beta-adrenergic stimulation by
      analyzing the frequency-dependence of the late I(Na). Fluoride augmented
      frequency-dependent reduction of the late I(Na), which was due to preferential
      delay of recovery of late I(Na). However, the increase in late I(Na) by fluoride
      at steady-state was more potent than the frequency-dependent reduction of late
      I(Na). SIGNIFICANCE: Different basic mechanisms participate in the QT interval
      shortening by pacing and beta-adrenergic stimulation in the LQT3.

PMID- 19167410
TI  - Studying health histories of cancer: a new model connecting cancer incidence and
      survival.
AB  - The results of recent experimental and epidemiological studies provide evidence
      on the connection between carcinogenesis, cancer progression, and aging. Existing
      models, however, are traditionally focused only on one of these aspects of health
      deterioration. In this paper, we derive a new model of cancer, which describes
      the connection between the ages at disease onset, the duration of disease, and
      life span of respective individuals. The model combines ideas used in the two
      hits model of carcinogenesis with those used in the Le Bras multistate model of
      aging with constant transition intensities. The model is used in the joint
      analyses of the US demographic mortality data and SEER data for selected cancers.
      The results show that the developed approach is capable of explaining links among
      health history data and provides useful insights on mechanisms of cancer
      occurrence, disease progression, other aging-related changes, and mortality.
      Further developments of this model are discussed.

PMID- 19167411
TI  - Effects of prey refuges on a predator-prey model with a class of functional
      responses: the role of refuges.
AB  - In this paper, the effects of refuges used by prey on a predator-prey interaction
      with a class of functional responses are studied by using the analytical
      approach. The refuges are considered as two types: a constant proportion of prey
      and a fixed number of prey using refuges. We will evaluate the effects with
      regard to the local stability of the interior equilibrium point, the values of
      the equilibrium density and the long-term dynamics of the interacting
      populations. The results show that the effects of refuges used by prey increase
      the equilibrium density of prey population while decrease that of predators. It
      is also proved that the effects of refuges can stabilize the interior equilibrium
      point of the considered model, and destabilize it under a very restricted set of
      conditions which is disagreement with previous results in this field.

PMID- 19167412
TI  - Role of sphingolipids in the cytoplasmic signaling of estrogens.
AB  - Recent studies have clearly demonstrated that estrogen signaling is not limited
      by the canonical 'genomic' pathway. Estrogens have been shown to interact with
      multiple cytoplasmic signaling networks including that of growth factors,
      cytokines, and the most recently recognised participants, sphingolipids.
      Sphingosine kinase (SphK), a key enzyme in metabolic pathways of sphingolipids,
      plays an important role in cell signaling and regulates a wide range of
      biological functions, including the actions of estrogens. Herein we briefly
      review current experimental evidence showing a critical involvement of
      sphingolipids in estrogen signaling, especially in breast cancer and vascular
      endothelial cells. In the current review we mainly focus on the SphK pathway and
      discuss the potential role of SphK and sphingolipids in the cellular biology of
      estrogens.

PMID- 19167413
TI  - Effects of epistasis and the evolution of genetic architecture: exact results for
      a 2-locus model.
AB  - We study a two-locus model of a quantitative trait with a continuum-of alleles
      and multilinear epistasis that evolves under mutation, selection, and genetic
      drift. We derive analytical results based on the so-called House of Gauss
      approximation for the genetic variance, the mean phenotype, and the mutational
      variance in the balance of the evolutionary forces. The analytical work is
      complemented by extensive individual-based computer simulations. We find that (1)
      analytical results are accurate in a large parameter space; (2) epistasis always
      reduces the equilibrium genetic variance, as predicted in earlier studies that
      exclude drift; (3) large-scale stochastic fluctuations and non-equilibrium
      phenomena like adaptive inertia can strongly influence the evolution of the
      genetic architecture of the trait.

PMID- 19167414
TI  - Trivalent methylated arsenical-induced phosphatidylserine exposure and apoptosis
      in platelets may lead to increased thrombus formation.
AB  - Trivalent methylated metabolites of arsenic, monomethylarsonous acid (MMA(III))
      and dimethylarsinous acid (DMA(III)), have been found highly reactive and toxic
      in various cells and in vivo animal models, suggesting their roles in the arsenic
      associated toxicity. However, their effects on cardiovascular system including
      blood cells, one of the most important targets for arsenic toxicity, remain
      poorly understood. Here we found that MMA(III) and DMA(III) could induce
      procoagulant activity and apoptosis in platelets, which play key roles in the
      development of various cardiovascular diseases (CVDs) through excessive thrombus
      formation. In freshly isolated human platelets, treatment of MMA(III) resulted in
      phosphatidylserine (PS) exposure, a hallmark of procoagulant activation,
      accompanied by distinctive apoptotic features including mitochondrial membrane
      potential disruption, cytochrome c release, and caspase-3 activation. These
      procoagulant activation and apoptotic features were found to be mediated by the
      depletion of protein thiol and intracellular ATP, and flippase inhibition by
      MMA(III), while the intracellular calcium increase or reactive oxygen species
      generation was not involved. Importantly, increased platelet procoagulant
      activity by MMA(III) resulted in enhanced blood coagulation and excessive
      thrombus formation in a rat in vivo venous thrombosis model. DMA(III) also
      induced PS-exposure with apoptotic features mediated by protein thiol depletion,
      which resulted in enhanced thrombin generation. In summary, we believe that this
      study provides an important evidence for the role of trivalent methylated arsenic
      metabolites in arsenic-associated CVDs, giving a novel insight into the role of
      platelet apoptosis in toxicant-induced cardiovascular toxicity.

PMID- 19167415
TI  - Impaired arsenic metabolism in children during weaning.
AB  - BACKGROUND: Methylation of inorganic arsenic (iAs) via one-carbon metabolism is a
      susceptibility factor for a range of arsenic-related health effects, but there is
      no data on the importance of arsenic metabolism for effects on child development.
      AIM: To elucidate the development of arsenic metabolism in early childhood.
      METHODS: We measured iAs, methylarsonic acid (MA) and dimethylarsinic acid (DMA),
      the metabolites of iAs, in spot urine samples of 2400 children at 18 months of
      age. The children were born to women participating in a population-based
      longitudinal study of arsenic effects on pregnancy outcomes and child
      development, carried out in Matlab, a rural area in Bangladesh with a wide range
      of arsenic concentrations in drinking water. Arsenic metabolism was evaluated in
      relation to age, sex, anthropometry, socio-economic status and arsenic exposure.
      RESULTS: Arsenic concentrations in child urine (median 34 microg/L, range 2.4-940
      microg/L), adjusted to average specific gravity of 1.009 g/mL, were considerably
      higher than that measured at 3 months of age, but lower than that in maternal
      urine. Child urine contained on average 12% iAs, 9.4% MA and 78% DMA, which
      implies a marked change in metabolite pattern since infancy. In particular, there
      was a marked increase in urinary %MA, which has been associated with increased
      risk of health effects. CONCLUSION: The arsenic metabolite pattern in urine of
      children at 18 months of age in rural Bangladesh indicates a marked decrease in
      arsenic methylation efficiency during weaning.

PMID- 19167416
TI  - The tumor-promoting activity of 2-acetylaminofluorene is associated with
      disruption of the p53 signaling pathway and the balance between apoptosis and
      cell proliferation.
AB  - The aromatic amine 2-acetylaminofluore (2-AAF) is a powerful complete genotoxic
      rat liver carcinogen that induces tumors without any additional interventions.
      While the tumor-initiating genotoxic activity of 2-AAF is well established, its
      tumor-promotion activity is far less understood. It is believed that the tumor
      promoting property of 2-AAF is associated with selective enhancement of cell
      replication and sustained suppression of apoptosis in initiated cells. In the
      present study, we investigated the underlying mechanisms of tumor-promoting
      events induced by 2-AAF-exposure. Male Sprague-Dawley rats were fed NIH-31 diet
      containing 0.02% of 2-AAF for 12 and 24 weeks, and the expression pattern of
      genes associated with the p53-signaling pathway and microRNA genes was determined
      in the livers of control and 2-AAF-fed rats. The results indicate that the tumor
      promoting property of 2-AAF during hepatocarcinogenesis is associated
      predominantly with the up-regulation of anti-apoptotic growth-related genes and
      down-regulation of expression of pro-apoptotic genes. This disrupts the balance
      between cell proliferation and apoptosis, which leads to consequential
      unrestricted cell proliferation, especially of initiated cells. Also, the long
      term-administration of 2-AAF resulted in disruption of regulatory miR-34a-p53
      feed-back loop that mediates apoptosis. This was evidenced by an increased
      expression of miR-34a in response to genotoxic effects of 2-AAF in the absence of
      p53 up-regulation, and loss of regulatory control of mir-34a on SIRT1 function.
      Additionally, the livers of 2-AAF-exposed rats were characterized by the
      substantial deregulation of expression of miR-18, miR-21, miR-182, and miR-200
      family, microRNAs involved in control of apoptosis/cell proliferation and cell
      cell contact pathways, two major pathways disrupted during the promotion stage of
      hepatocarcinogenesis.

PMID- 19167417
TI  - Analysis of hepatic gene expression during fatty liver change due to chronic
      ethanol administration in mice.
AB  - Chronic consumption of ethanol can cause cumulative liver damage that can
      ultimately lead to cirrhosis. To explore the mechanisms of alcoholic steatosis,
      we investigated the global intrahepatic gene expression profiles of livers from
      mice administered alcohol. Ethanol was administered by feeding the standard
      Lieber-DeCarli diet, of which 36% (high dose) and 3.6% (low dose) of the total
      calories were supplied from ethanol for 1, 2, or 4 weeks. Histopathological
      evaluation of the liver samples revealed fatty changes and punctate necrosis in
      the high-dose group and ballooning degeneration in the low-dose group. In total,
      292 genes were identified as ethanol responsive, and several of these differed
      significantly in expression compared to those of control mice (two-way ANOVA;
      p<0.05). Specifically, the expression levels of genes involved in hepatic lipid
      transport and metabolism were examined. An overall net increase in gene
      expression was observed for genes involved in (i) glucose transport and
      glycolysis, (ii) fatty acid influx and de novo synthesis, (iii) fatty acid
      esterification to triglycerides, and (iv) cholesterol transport, de novo
      cholesterol synthesis, and bile acid synthesis. Collectively, these data provide
      useful information concerning the global gene expression changes that occur due
      to alcohol intake and provide important insights into the comprehensive
      mechanisms of chronic alcoholic steatosis.

PMID- 19167418
TI  - Colour-space distortion in women who are heterozygous for colour deficiency.
AB  - We examined colour perception among a group of women heterozygous for colour
      vision deficiency. Judgements of colour dissimilarity were collected by
      presenting colour stimuli in groups of three for odd-one-out decisions. The
      judgements were summarised as one consensus colour space for the heterozygotes
      and another for age-matched controls. Individual differences MDS was also
      applied, resulting in a single colour space which can be adjusted to fit each
      subject's responses individually by compressing it along its axes. Heterozygous
      women showed a trend towards colour-space compression in a red-green dimension,
      or reduced salience of that dimension compared to controls, though less extreme
      than found in overt colour deficiency.

PMID- 19167419
TI  - Orientation-specific contextual modulation of the fMRI BOLD response to luminance
      and chromatic gratings in human visual cortex.
AB  - The responses of orientation-selective neurons in primate visual cortex can be
      profoundly affected by the presence and orientation of stimuli falling outside
      the classical receptive field. Our perception of the orientation of a line or
      grating also depends upon the context in which it is presented. For example, the
      perceived orientation of a grating embedded in a surround tends to be repelled
      from the predominant orientation of the surround. Here, we used fMRI to
      investigate the basis of orientation-specific surround effects in five
      functionally-defined regions of visual cortex: V1, V2, V3, V3A/LO1 and hV4. Test
      stimuli were luminance-modulated and isoluminant gratings that produced responses
      similar in magnitude. Less BOLD activation was evident in response to gratings
      with parallel versus orthogonal surrounds across all the regions of visual cortex
      investigated. When an isoluminant test grating was surrounded by a luminance
      modulated inducer, the degree of orientation-specific contextual modulation was
      no larger for extrastriate areas than for V1, suggesting that the observed
      effects might originate entirely in V1. However, more orientation-specific
      modulation was evident in extrastriate cortex when both test and inducer were
      luminance-modulated gratings than when the test was isoluminant; this difference
      was significant in area V3. We suggest that the pattern of results in
      extrastriate cortex may reflect a refinement of the orientation-selectivity of
      surround suppression specific to the colour of the surround or, alternatively,
      processes underlying the segmentation of test and inducer by spatial phase or
      orientation when no colour cue is available.

PMID- 19167420
TI  - Anxiolytic-like profile of mirtazapine in rat conditioned fear stress model:
      Functional significance of 5-hydroxytryptamine 1A receptor and alpha1-adrenergic
      receptor.
AB  - Mirtazapine is an antidepressant with a unique mechanism of action and has been
      categorized as a Noradrenergic and Specific Serotonergic Antidepressant (NaSSA).
      Although numerous clinical trials suggested the usefulness of mirtazapine for not
      only major depressive disorders but also a variety of anxiety disorders, efficacy
      studies in animal anxiety models have been rarely reported. The present study
      investigated a potential anxiolytic-like profile of mirtazapine in rat
      conditioned fear stress model. A 5-hydroxytryptamine (5-HT) 1A receptor partial
      agonist, buspirone (1-5 mg/kg) exhibited a significant reduction in freezing
      time, and its maximal effect was reversed by a selective 5-HT(1A) antagonist, WAY
      100635 (1 mg/kg). Mirtazapine (1-10 mg/kg) also reduced the freezing time in a
      dose-related fashion, a substantial proportion (approx. 50%) of which was
      likewise antagonized by WAY-100635 (1 mg/kg). Mianserin (1-30 mg/kg), a
      structural analogue for mirtazapine, was ineffective. Furthermore, co
      administration of alpha1 adrenoceptor antagonist, prazosin (0.03 mg/kg)
      completely reversed mirtazapine (10 mg/kg)-induced reduction of freezing time.
      These findings represent the first demonstration that the anxiolytic-like action
      of mirtazapine involves activation of 5-HT(1A) receptor and alpha1 adrenoceptor
      to different extents, and are compatible with one aspect of mirtazapine's
      pharmacological profile as NaSSA.

PMID- 19167421
TI  - Synergism between NSAIDs in the orofacial formalin test in mice.
AB  - Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are used to relieve
      acute and chronic pain. The purpose of this study was to determine the degree of
      interaction between dexketoprofen and NSAID examples of COXs inhibitors using the
      isobolographic analysis in the formalin orofacial test in mice. The drugs, i.p.,
      induced a dose-dependent antinociception with different potencies in both test
      phases. Combinations of dexketoprofen with naproxen, nimesulide, ibuprofen or
      paracetamol on the basis of the fixed ratio (1:1) of their ED(50)'s values alone
      demonstrated synergism in both phases. This is important since the orofacial pain
      is a test not currently used in mice; the drugs are all analgesic for humans and
      phase II is representative of inflammatory pain. The synergism was: COX-3>COX
      2>COX-1 inhibitors, this is particularly interesting since the inhibitor of COX
      3, paracetamol, displayed a robust anti-inflammatory activity in an assay of
      acute and inflammatory pain that mimics inflammatory pain in humans. In
      conclusion, the synergism of the dexketoprofen/NSAID combinations may improve
      this type of therapeutic profile, since with low doses of the components, side
      effects are not likely to occur, and they may be used in long-term treatments.

PMID- 19167422
TI  - Defining a strategy to evaluate cervical cancer prevention and early detection in
      the era of HPV vaccination.
AB  - OBJECTIVE: The purpose of this paper is to outline the short-, medium- and long
      term requirements of a strategy to evaluate the impact of HPV immunization and to
      define a framework to facilitate planning and evaluation. METHOD: This strategy
      was developed in Ontario from January to August 2008. Literature review was
      completed to assess existing material relevant to vaccine evaluation, and HPV
      vaccine specifically. Scientists and epidemiologists within our organization
      attended meetings to brainstorm and identify key requirements for vaccine
      evaluation. Other selected internal and external experts were consulted to review
      preliminary lists of potential indicators and questions for inclusion in an
      evaluation strategy. RESULTS: Results are reported in three sections--literature
      review, proposed evaluation framework and data requirements. CONCLUSION: The
      first vaccine evaluation strategy that integrates primary and secondary
      prevention of cervical cancer is presented. Among women who are neither screened
      nor immunized, customized interventions will be required to ensure that they are
      aware of potential risks and benefits. This evaluation strategy may serve as a
      useful outline for jurisdictions in Canada and elsewhere. This new paradigm of
      combined primary and secondary intervention will encourage cooperation for
      effective evaluation of an integrated approach for control of cervical cancer and
      other HPV-related disease.

PMID- 19167423
TI  - Identification and characterization of Streptomyces ghanaensis ATCC14672
      integration sites for three actinophage-based plasmids.
AB  - Streptomyces ghanaensis produces the antibiotic moenomycin A, which is the only
      known direct inhibitor of bacterial peptidoglycan glycosyltransferases
      (transglycosylases). Recent progress in understanding moenomycin biosynthesis
      opens the door to the generation of novel moenomycins via biocombinatorial
      approaches. To realize the promise of such an approach, one needs better
      knowledge of the S. ghanaensis genome and diverse genetic tools for stable
      expression of recombinant constructs in this strain. In this respect, we report
      the intergeneric Escherichia coli-S. ghanaensis conjugal transfer of plasmids
      pRT801 and pSOK804 based on the actinophage BT1 and VWB integrase systems,
      respectively. The attB sites for these two plasmids and for pSET152 were
      characterized. In particular, sequencing revealed that a putative Arg-tRNA gene
      serves as an integration site for both phage VWB and pSAM2-like actinomycete
      integrative and conjugative element recently suggested to be widespread and
      functional in actinomycetes. The stability of the studied plasmids and their
      neutrality with respect to antibiotic production warrant their use for
      manipulations of S. ghanaensis genome.

PMID- 19167424
TI  - Contribution of the activation of satellite glia in sensory ganglia to
      pathological pain.
AB  - Peripheral tissue injury/inflammation can alter the properties of somatic sensory
      pathways, resulting in behavioral hypersensitivity and pathological and/or
      chronic pain, including increased responses to pain caused by both noxious
      stimuli (hyperalgesia) and normally innocuous stimuli (allodynia). Although there
      are increasing reports that glia in the spinal cord contribute to the maintenance
      of pathological pain, recent evidence suggests that activation of satellite glia
      in sensory ganglia may also play an important role in the development of
      hyperalgesia and allodynia. There is evidence that non-synaptically released
      chemical mediators derived from both neurons and satellite glia may trigger
      chronic pain via autocrine and/or paracrine mechanisms and that augmented
      excitability of primary afferent neurons results in changes in central pain
      signaling neurons (central sensitization). The focus of the present review is on
      the contribution of the activation of satellite glia in sensory ganglia to
      pathological pain. In addition, we discuss potential therapeutic targets in
      satellite glia-neuronal interactions for the prevention of pathological pain.

PMID- 19167426
TI  - Cognitive motor processes: the role of motor imagery in the study of motor
      representations.
AB  - Motor imagery is viewed as a window to cognitive motor processes and particularly
      to motor control. Mental simulation theory [Jeannerod, M., 2001. Neural
      simulation of action: a unifying mechanism for motor cognition. NeuroImage 14,
      103-109] stresses that cognitive motor processes such as motor imagery and action
      observation share the same representations as motor execution. This article
      presents an overview of motor imagery studies in cognitive psychology and
      neuroscience that support and extend predictions from mental simulation theory.
      In general, behavioral data as well as fMRI and TMS data demonstrate that motor
      areas in the brain play an important role in motor imagery. After discussing
      results on a close overlap between mental and actual performance durations, the
      review focuses specifically on studies reporting an activation of primary motor
      cortex during motor imagery. This focus is extended to studies on motor imagery
      in patients. Motor imagery is also analyzed in more applied fields such as mental
      training procedures in patients and athletes. These findings support the notion
      that mental training procedures can be applied as a therapeutic tool in
      rehabilitation and in applications for power training.

PMID- 19167427
TI  - TTC, fluoro-Jade B and NeuN staining confirm evolving phases of infarction
      induced by middle cerebral artery occlusion.
AB  - Considerable debate exists in the literature on how best to measure infarct
      damage and at what point after middle cerebral artery occlusion (MCAO) infarct is
      histologically complete. As many researchers are focusing on more chronic
      endpoints in neuroprotection studies it is important to evaluate histological
      damage at later time points to ensure that standard methods of tissue injury
      measurement are accurate. To compare tissue viability at both acute and sub-acute
      time points, we used 2,3,5-triphenyltetrazolium chloride (TTC), Fluoro-Jade B,
      and NeuN staining to examine the evolving phases of infarction induced by a 90
      min MCAO in mice. Stroke outcomes were examined at 1.5h, 6h, 12h, 24h, 3d, and 7d
      after MCAO. There was a time-dependent increase in infarct volume from 1.5h to
      24h in the cortex, followed by a plateau from 24h to 7d after stroke. Striatal
      infarcts were complete by 12h. Fluoro-Jade B staining peaked at 24h and was
      minimal by 7d. Our results indicated that histological damage as measured by TTC
      and Fluoro-Jade B reaches its peak by 24h after stroke in a reperfusion model of
      MCAO in mice. TTC staining can be accurately performed as late as 7d after
      stroke. Neurological deficits do not correlate with the structural lesion but
      rather transient impairment of function. As the infarct is complete by 24h and
      even earlier in the striatum, even the most efficacious neuroprotective therapies
      are unlikely to show any efficacy if given after this point.

PMID- 19167428
TI  - Unbiased estimation of precise temporal correlations between spike trains.
AB  - A key issue in systems neuroscience is the contribution of precise temporal inter
      neuronal interactions to information processing in the brain, and the main
      analytical tool used for studying pair-wise interactions is the cross-correlation
      histogram (CCH). Although simple to generate, a CCH is influenced by multiple
      factors in addition to precise temporal correlations between two spike trains,
      thus complicating its interpretation. A Monte-Carlo-based technique, the
      jittering method, has been suggested to isolate the contribution of precise
      temporal interactions to neural information processing. Here, we show that
      jittering spike trains is equivalent to convolving the CCH derived from the
      original trains with a finite window and using a Poisson distribution to estimate
      probabilities. Both procedures over-fit the original spike trains and therefore
      the resulting statistical tests are biased and have low power. We devise an
      alternative method, based on convolving the CCH with a partially hollowed window,
      and illustrate its utility using artificial and real spike trains. The modified
      convolution method is unbiased, has high power, and is computationally fast. We
      recommend caution in the use of the jittering method and in the interpretation of
      results based on it, and suggest using the modified convolution method for
      detecting precise temporal correlations between spike trains.

PMID- 19167425
TI  - Chloride regulation in the pain pathway.
AB  - Melzack and Wall's Gate Control Theory of Pain laid the theoretical groundwork
      for a role of spinal inhibition in endogenous pain control. While the Gate
      Control Theory was based on the notion that spinal inhibition is dynamically
      regulated, mechanisms underlying the regulation of inhibition have turned out to
      be far more complex than Melzack and Wall could have ever imagined. Recent
      evidence indicates that an exquisitely sensitive form of regulation involves
      changes in anion equilibrium potential (E(anion)), which subsequently impacts
      fast synaptic inhibition mediated by GABA(A), and to a lesser extent, glycine
      receptor activation, the prototypic ligand gated anion channels. The cation
      chloride co-transporters (in particular NKCC1 and KCC2) have emerged as proteins
      that play a critical role in the dynamic regulation of E(anion) which in turn
      appears to play a critical role in hyperalgesia and allodynia following
      peripheral inflammation or nerve injury. This review summarizes the current state
      of knowledge in this area with particular attention to how such findings relate
      to endogenous mechanisms of hyperalgesia and allodynia and potential applications
      for therapeutics based on modulation of intracellular Cl(-) gradients or
      pharmacological interventions targeting GABA(A) receptors.

PMID- 19167429
TI  - Theoretical evaluations of therapeutic systemic and local cerebral hypothermia.
AB  - PURPOSE: To simulate cerebral temperature behaviour with hypothermia treatment
      applying different cooling devices and to find the optimal brain temperature
      monitoring. METHODS: Models based on hourly temperature values recorded in
      patients with severe aneurysmal subarachnoid hemorrhage, taking MRI data, thermal
      conductive properties, metabolism and blood flow into account were applied to
      different scenarios of hypothermia. RESULTS: Systemic hypothermia by endovascular
      cooling leads to an uniform temperature decrease within the brain tissue. Cooling
      with head caps lead to 33 degrees C only in the superficial brain while the deep
      brain remains higher than 36 degrees C. Cooling with neckbands lead to 35.8
      degrees C for dry and 32.8 degrees C for wet skin in the deep brain. CONCLUSIONS:
      With head caps temperatures below 36 degrees C cannot be reached in the deep
      brain tissue, whereas neckbands, covering the carotid triangles, may lead to
      hypothermic temperatures in the deep brain tissue. Temperature sensors have to be
      applied at least 2 cm below the cortical surface to give values representative
      for deep brain tissue.

PMID- 19167430
TI  - A comparison of human brain dissection by drill versus saw on nucleic acid
      quality.
AB  - This study examined the effect of two dissection techniques on the quality of
      human brain specimens. Frozen cerebellar samples were obtained from postmortem
      brains of 10 subjects free from neurological and psychiatric disease. These
      tissues were tested for RNA and DNA concentration and quality after being
      dissected with either an electric dental drill or a small handsaw. RNA and DNA
      were extracted separately from each sample, and the concentrations and quality of
      each were measured. We found that dissection technique does not significantly
      affect RNA or DNA quality/yield. RNA and DNA yields, as well as RNA integrity
      showed no significant differences between the two dissection techniques.
      Therefore, these results support the use of a high-speed hand-held electric
      dental drill as an efficient and anatomically precise means of human brain
      dissection without compromising tissue quality.

PMID- 19167431
TI  - Infection and regulation of the immune response.
AB  - Several established populations with low allergy susceptibility have been
      identified and may be exploited for further evaluation. A variety of factors
      seems to offer some protection from allergy, including exposure to viral and/or
      bacterial compounds and restrictive use of antibiotics and antipyretics. There
      are probably more factors and mechanisms to discover, and the ultimate goal
      remains to identify a single/a group of protective factor(s) that might be
      employed for effective and safe prevention strategies in high allergy
      susceptibility populations. It should be noted, however, that the association of
      allergy prevalence and a loss of allergy protective factors described above seems
      to be more pronounced regarding respiratory allergy than other phenotypes of the
      atopic syndrome.

PMID- 19167432
TI  - Delivery of endocytosed membrane proteins to the lysosome.
AB  - The delivery of proteins from the plasma membrane to the lysosome for degradation
      is essential for normal cellular function. There is now a good understanding of
      the protein complexes involved in sorting proteins at the plasma membrane and
      into the intralumenal vesicles of the multi-vesicular body. A combination of cell
      free content mixing assays and live-cell imaging has dissected out the final step
      in delivery of macromolecules to the lysosome from the multi-vesicular body and
      provided insights into the molecular mechanisms by which late endosomes and
      lysosomes exchange lumenal contents. The endocytic pathway has provided a
      platform with which to understand the autophagic and phagocytic pathways, but the
      fine details of how traffic through these pathways is regulated remain to be
      determined.

PMID- 19167433
TI  - Geometric control of tissue morphogenesis.
AB  - Morphogenesis is the dynamic and regulated change in tissue form that leads to
      creation of the body plan and development of mature organs. Research over the
      past several decades has uncovered a multitude of genetic factors required for
      morphogenesis in animals. The behaviors of individual cells within a developing
      tissue are determined by combining these genetic signals with information from
      the surrounding microenvironment. At any point in time, the local
      microenvironment is influenced by macroscale tissue geometry, which sculpts long
      range signals by affecting gradients of morphogens and mechanical stresses. The
      geometry of a tissue thus acts as both a template and instructive cue for further
      morphogenesis.

PMID- 19167435
TI  - New selective and differential chromogenic agar medium, chromID VRE, for
      screening vancomycin-resistant Enterococcus species.
AB  - This study aimed to evaluate the usefulness of a novel differential culture
      medium, chromID VRE agar, for the isolation of VRE in a clinical laboratory. It
      was shown that ChromID VRE agar may be useful for rapid and selective isolation
      of VRE especially after inclusion of broth enrichment step.

PMID- 19167434
TI  - Role and regulation of autophagy in cancer.
AB  - Autophagy is an evolutionarily conserved process whereby cytoplasm and cellular
      organelles are degraded in lysosomes for amino acid and energy recycling.
      Autophagy is a survival pathway activated in response to nutrient deprivation and
      other stressful stimuli, such as metabolic stress and exposure to anticancer
      drugs. However, autophagy may also result in cell death, if it proceeds to
      completion. Defective autophagy is implicated in tumorigenesis, as the essential
      autophagy regulator beclin 1 is monoallelically deleted in human breast, ovarian
      and prostate cancers, and beclin 1(+/-) mice are tumor-prone. How autophagy
      suppresses tumorigenesis is under intense investigation. Cell-autonomous
      mechanisms, involving protection of genome integrity and stability, and a non
      cell-autonomous mechanism, involving suppression of necrosis and inflammation,
      have been discovered so far. The role of autophagy in treatment responsiveness is
      also complex. Autophagy inhibition concurrently with chemotherapy or radiotherapy
      has emerged as a novel approach in cancer treatment, as autophagy-competent tumor
      cells depend on autophagy for survival under drug- and radiation-induced stress.
      Alternatively, autophagy stimulation and preservation of cellular fitness by
      maintenance of protein and organelle quality control, suppression of DNA damage
      and genomic instability, and limitation of necrosis-associated inflammation may
      play a critical role in cancer prevention.

PMID- 19167436
TI  - Parvalbumin neurons in the forebrain as revealed by parvalbumin-Cre transgenic
      mice.
AB  - Neurons expressing the calcium-binding protein parvalbumin (PV) constitute an
      abundant subpopulation of GABAergic neurons in the cerebral cortex. However, PV
      is not unique to the GABAergic neurons of the forebrain, but is also expressed in
      a small number of pyramidal neurons and in a large number of thalamic neurons. In
      order to summarize the PV neurons in the forebrain, we employed the PV-Cre
      transgenic mice in the present study. In the progeny of crossbreed between PV-Cre
      mice and GFP-Cre reporter mice, we found that the GFP-positive neurons include
      many excitatory neurons in the neocortex and the thalamus as well as GABAergic
      neurons in the cerebral cortex and basal ganglia. All the reported PV-positive
      GABAergic neurons in the cerebral cortex and the basal ganglia seemed to be
      included in the GFP-positive cells. We found GFP-positive layer V pyramidal
      neurons inhabit a broader neocortical area than was previously reported. They
      were located in the primary somatosensory, motor, and visual areas. The
      somatosensory area of the neocortex contained the greatest number of PV-positive
      pyramidal neurons. A large number of thalamic relay neurons and virtually all the
      reticular thalamic neurons appeared as GFP-positive. Thalamic relay nucleus and a
      neocortical area for the same modality corresponded and seemed to contain a
      characteristic amount of PV-positive excitatory neurons.

PMID- 19167438
TI  - Kainic acid intraocular injections during the postnatal critical period induce
      plastic changes in the visual system.
AB  - Changes in the retino-collicular projection and in the number of optic nerve (ON)
      axons in adult rats were analyzed after partial loss of retinal ganglion cells
      (RGCs), induced by intravitreal injections of kainic acid (KA) on postnatal days
      2-3 (P2-P3) or 10-12 (P10-P12). KA injected at P2-P3 decreased the volume of the
      adult contralateral superior colliculus (SC) and the density of the retino
      collicular contralateral projection, but maintained the neonatal pattern in the
      ipsilateral projection from the un-injected eye. ON axon number was significantly
      increased in the un-injected eye but decreased in the KA-injected eye. Thus,
      restriction of the ipsilateral retino-collicular projection and RGC death in the
      un-injected eye are modified by KA at P2-P3, during the postnatal critical
      period, but not at P10-P12, after it is over. We suggest that, in the SC
      contralateral to the KA-injected eye, the disappearance of axon terminals
      belonging to RGC killed by KA would decrease competition between ipsilateral and
      contralateral terminals, thus contributing to maintaining the neonatal pattern in
      the ipsilateral retino-collicular projection. The reduction in RGC death in the
      un-injected eye could also be related to the disappearance of RGC terminals in
      the contralateral SC, which would have increased neurotrophic factor
      availability.

PMID- 19167437
TI  - Splicing variations in the ligand-binding domain of ApoER2 results in functional
      differences in the binding properties to Reelin.
AB  - Reelin plays critical roles in brain formation by binding to apolipoprotein E
      receptor 2 (ApoER2) and very low-density lipoprotein receptor. Several isoforms
      and fragments of Reelin are generated by alternative splicing and proteolytic
      cleavage. In addition, two splice variants of ApoER2 have been recognized,
      namely, LA1237 and LA12378, that differ in the number of ligand-binding type A
      (LA) repeats. Here, we quantitatively investigated the affinity between various
      isoforms/fragments of Reelin and the ApoER2 splice variants. ApoER2-LA1237 bound
      rather strongly to the Reelin central fragment than to the fragment bearing
      Reelin repeat 8 (RR8). ApoER2-LA12378 bound comparably to all Reelin fragments
      without the C-terminal region. These findings suggest that LA8 of ApoER2 and RR8
      interfere with the interaction between the Reelin central fragment and ApoER2.
      Using a monoclonal antibody that only recognizes ApoER2-LA12378, we found that
      this variant of ApoER2 was expressed in the cerebral cortical wall and in the
      internal granule cells of the cerebellum during development. Primary-cultured
      cortical neurons did not express ApoER2-LA12378, and the extent of signal
      activation by Reelin fragments was well correlated with their affinity for ApoER2
      LA1237. Therefore, proteolytic cleavage of Reelin and alternative splicing of
      ApoER2 may be involved in the fine regulation of Reelin signaling.

PMID- 19167439
TI  - Electrical coupling between hippocampal astrocytes in rat brain slices.
AB  - Gap junctions in astrocytes play a crucial role in intercellular communication by
      supporting both biochemical and electrical coupling between adjacent cells.
      Despite the critical role of electrical coupling in the network organization of
      these glial cells, the electrophysiological properties of gap junctions have been
      characterized in cultures while no direct evidence has been sought in situ. In
      the present study, gap-junctional currents were investigated using simultaneous
      dual whole-cell patch-clamp recordings between astrocytes from rat hippocampal
      slices. Bidirectional electrotonic coupling was observed in 82% of the cell pairs
      with an average coupling coefficient of 5.1%. Double patch-clamp analysis
      indicated that junctional currents were independent of the transjunctional
      voltage over a range from -100 to +110 mV. Interestingly, astrocytic electrical
      coupling displayed weak low-pass filtering properties compared to neuronal
      electrical synapses. Finally, during uncoupling processes triggered by either the
      gap-junction inhibitor carbenoxolone or endothelin-1, an increase in the input
      resistance in the injected cell paralleled the decrease in the coupling
      coefficient. Altogether, these results demonstrate that hippocampal astrocytes
      are electrically coupled through gap-junction channels characterized by
      properties that are distinct from those of electrical synapses between neurons.
      In addition, gap-junctional communication is efficiently regulated by endogenous
      compounds. This is taken to represent a mode of communication that may have
      important implications for the functional role of astrocyte networks in situ.

PMID- 19167440
TI  - Disruption of the NADPH-dependent glutamate dehydrogenase affects the morphology
      of two industrial strains of Penicillium chrysogenum.
AB  - New morphological aspects of Penicillium chrysogenum were found during
      physiological characterisation of two NADPH-dependent glutamate dehydrogenase
      mutant strains. A morphological characterisation of the previously constructed
      strains, together with the two beta-lactam producing industrial recipient
      strains, was conducted. The reference strains showed a compact structure with
      highly branched hyphal elements whereas the morphology of the DeltagdhA strains
      consisting of long elongated hyphal elements with few branches. On solid medium,
      the hyphal growth unit (length) increased from an average of 47 microm tip(-1) in
      the reference strains to 117 microm tip(-1) in the DeltagdhA strains and in
      submerged cultures a decrease of 18% in branching frequency was measured due to
      the gdhA deletion. P. chrysogenum Wis 54-1255, the ancestor of most production
      strains was also characterised and this strain showed morphology similar to the
      industrial strains. Interestingly, the constructed strains showed morphology
      similar to wild type Aspergillus nidulans another species carrying the penicillin
      biosynthetic cluster. Thus, the results showed that elimination of glutamate
      dehydrogenase activity in high producing strains of P. chrysogenum has a radical
      impact on morphology.

PMID- 19167441
TI  - Analysis of the leader proteinase (L(pro)) region of type A foot-and-mouth
      disease virus with due emphasis on phylogeny and evolution of the emerging
      VP3(59)-deletion lineage from India.
AB  - Genotype inclusive grouping of Indian type A isolates as observed in 1D region
      based phylogeny was distorted at complete L(pro) region, where the VP3(59)
      deletion group lineages of genotype VII clustered away from both genotypes VII
      and VI, confirming its uniqueness and independent evolution of L(pro) and 1D
      region. Akin to the 1D region, this deletion group is gradually diverging
      genetically even at L region forming more number of lineages and inter-lineage
      distance at L region is considerably more than that for 1D region. The deletion
      group is restricted to India only as none of the exotic sequences clustered
      within this group. Notably, L protein exhibited variability comparable to
      external capsid proteins as evident from its high d(N)/d(S) ratio (0.105), number
      of variable amino acid positions (41%), low Ts/Tv ratio (3.47) and alignment
      revealed N-terminal region, beta2 sheet and C-terminal extension to be extremely
      variable. Basic residues at P1, P3 and only leucine at P2 were predicted to
      provide an optimum autocatalytic cleavage site at L/P1 junction. All of the eight
      sites identified to be under positive selection revealed aa substitutions of
      varied physicochemical properties and at two positions lineage specific
      signatures were observed, which supports the contention that lineages are
      evolving under differential selection pressure to adapt to the varied ecological
      environment.

PMID- 19167442
TI  - Use of CpG oligonucleotides in treatment of asthma and allergic disease.
AB  - In the last several decades, there has been a marked increase in the prevalence
      of atopic disorders including asthma in "Western" societies; a relationship has
      been identified between lack of early-life exposure to microbes or microbial
      products and increased susceptibility to atopic disorders. The innate immune
      system is activated by early microbial exposures, many of which utilize one of
      the Toll-like receptors, and there has been significant interest in studying how
      ligation of TLRs may be therapeutically useful. CpG oligonucleotides (CpG-ODN,
      resembling bacterial DNA) engage TLR-9 on B-cells, dendritic cells and other cell
      types, resulting in a cascade that includes induction of Th1-type and T
      regulatory-type immune responses. Preclinical models of asthma have demonstrated
      that CpG-ODN are potent inhibitors of atopic responses, suppressing Th2 cytokine
      and, reducing airway eosinophilia, systemic levels of IgE, and bronchial
      hyperreactivity-in short the critical attributes of the asthmatic phenotype. In
      models of chronic allergen exposure, CpG-ODN are also effective at preventing the
      development of airway remodeling. In established asthma, CpG-ODN can reverse
      manifestations of disease, both when used alone or in combination with allergen
      immunotherapy. Early clinical trials have had mixed results, including a
      significant benefit when CpG-ODN were conjugated to ragweed allergen in an
      allergic rhinitis immunotherapy study, but only limited efficacy seen when
      administered prior to allergen challenge in asthmatics. Further study of CpG-ODNs
      for the treatment of asthma and other atopic disorders is warranted by existing
      data.

PMID- 19167443
TI  - Family-based analysis of tumor necrosis factor and lymphotoxin-alpha tag
      polymorphisms with type 1 diabetes in the population of South Croatia.
AB  - Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) are cytokines with a wide
      range of inflammatory and immunomodulatory activities. Type 1 diabetes is an
      autoimmune disease characterized by destruction of insulin-producing pancreatic
      beta cells. The aim of the present study was to evaluate the association of
      polymorphisms in the TNF/LTA gene region with susceptibility to type 1 diabetes.
      We investigated 11 TNF/LTA tag polymorphisms, designed to capture the majority of
      common variation in the region, in 160 trio families from South Croatia. We
      observed overtransmission of alleles from parents to affected child at five
      variants: (rs909253, allele C, p = 1.2x10(-4); rs1041981, allele A, p = 1.1x10(
      4); rs1800629 (G-308A), allele A, p = 1.2x10(-4); rs361525 (G-238A), allele G, p
      = 8.2x10(-3) and rs3093668, allele G, p = 0.014). We also identified
      overtransmission of the rs1800629(G-308A)-rs361525(G-238A) A-G haplotype, p =
      2.384x10(-5). The present study found an association of the TNF/LTA gene region
      with type 1 diabetes. A careful assessment of TNF/LTA variants adjusted for
      linkage disequilibrium with HLA loci is needed to further clarify the role of
      these genes in type 1 diabetes susceptibility in the population of South Croatia.

PMID- 19167444
TI  - Family-based transmission analysis of HLA genetic markers in Sardinian children
      with autistic spectrum disorders.
AB  - Analyses of a 6-Mb region spanning the human leukocyte antigen (HLA) region from
      the HLA-DR to the HFE gene were performed in 37 families of Sardinian ancestry,
      all of whom had at least one autistic child, to identify genetic markers
      associated with autism spectrum disorders (ASD) development. In particular, four
      microsatellites (MIB, D6S265, MOGc, and D6S2239) and three single-nucleotide
      polymorphisms (SNPs; two in positions -308 and -238 in the promoter of the TNF
      alpha and SNP rs2857766 [V142L] in exon 3 of the MOG gene) were analyzed. An
      intrafamilial case-control method (affected family-based controls) and
      transmission disequilibrium test analysis were used to evaluate the association
      of microsatellite and SNP markers with ASD-affected children. Results indicated
      positive associations with ASD for D6S265*220 (p < 0.01) and MOGc*131 (p < 0.05)
      and negative associations for MOGc*117 and MIB*346 alleles (p < 0.01) in ASD
      children. Polymorphism haplotype analysis indicated that D6S265 allele *220 and
      MOGc allele *131 were significantly more likely to be transmitted together, as a
      whole haplotype, to ASD children (p < 0.05). Conversely, the D6S265*224-MOGc*117
      rs2857766(G) haplotype was significantly less frequently transmitted to ASD
      children (p < 0.01). The results present novel gene markers, reinforcing the
      hypothesis that genetic factors play a pivotal role in the pathogenesis of ASD.

PMID- 19167445
TI  - Identification and characterization of 2 HIV-1 Gag immunodominant epitopes
      restricted by Asian HLA allele HLA-B*4801.
AB  - HLA-B*4801 is frequently found in Asian populations but rarely in Caucasian or
      African populations. Although HLA-B*4801-restricted human immunodeficiency virus
      1 (HIV-1) epitopes would be useful for acquired immune deficiency syndrome (AIDS)
      vaccine development in Asia, they have not been reported so far. In the present
      study, we sought to identify HLA-B*4801-restricted HIV-1 epitopes by using 17-mer
      overlapping peptides derived from HIV-1 Gag, Pol, and Nef as well as 8- to 11-mer
      truncated peptides, and thereby identified two HLA-B*4801-restricted Gag
      epitopes. These epitope-specific CD8(+) T cells strongly responded to HIV-1
      infected cells expressing HLA-B*4801, confirming that these Gag epitopes were
      endogenously presented by HLA-B*4801. These epitope-specific CD8(+) T cells were
      elicited in five of the seven tested chronically HIV-1-infected individuals with
      HLA-B*4801, suggesting them to be immunodominant epitopes. These epitopes will be
      useful for the studies of AIDS immunopathogenesis and the development of an HIV-1
      vaccine in Asia.

PMID- 19167446
TI  - Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to
      mixtures of dietary phytoestrogens.
AB  - Combinations of estrogen receptor agonists have been shown to exert more potent
      effects than single compounds in many single-endpoint bioassays. However, to our
      knowledge, it has never been tested how genome-wide expression programs are
      shaped by the interplay of multiple estrogenic stimuli. In view of the abundance
      of dietary phytoestrogens, we selected binary mixtures of these phytochemicals to
      determine their global impact using high-density DNA microarrays. MCF7 cells, a
      frequent in vitro model for molecular processes associated with breast cancer,
      were exposed to a sub-saturating concentration of coumestrol either alone or in
      combination with analogs that exhibit 1000-fold lower estrogen receptor activity.
      As expected, in the presence of coumestrol, the induction of many estrogen
      sensitive genes was not further increased by the addition of resveratrol or
      enterolactone. However, it was surprising to find that these weak phytoestrogens,
      when combined with coumestrol in equal concentrations, were able to more than
      double the number of significantly regulated transcripts. Thus, phytoestrogens
      with low receptor affinity interact with other estrogenic agonists to generate
      more widespread expression fingerprints. This effect involving the number of
      susceptible transcripts instead of their amplitude of induction remains
      undetected if mixtures are evaluated with conventional bioassays.

PMID- 19167447
TI  - Possible contribution of rubiadin, a metabolite of madder color, to renal
      carcinogenesis in rats.
AB  - Madder color (MC) has been shown to exert carcinogenic potential in the rat
      kidney in association with degeneration, karyomegaly, increased cell
      proliferation of renal tubule cells and increased renal 8-OHdG levels. To clarify
      the causal relationship of components and metabolites of MC to renal
      carcinogenesis, male F344 rats were fed lucidin-3-O-primeveroside (LuP) or
      alizarin (Alz), and the genotoxic LuP metabolites lucidin (Luc) or rubiadin (Rub)
      for up to 26 weeks. After one week and four weeks, Luc did not induce any renal
      changes. In contrast, after one week, cortical tubule degeneration was apparent
      in the Alz and LuP groups, and cytoplasmic swelling with basophilic change and
      karyomegaly in the outer medulla was observed only in the Rub group. LuP and Rub
      increased the proliferative activity of tubule cells in the outer medulla, and
      Alz and LuP increased renal 8-OHdG levels. After 26 weeks, Rub but not Alz
      induced atypical tubules, a putative preneoplastic lesion, and karyomegaly in the
      outer medulla. These results indicate that Rub may be a potent carcinogenic
      metabolite of MC, targeting proximal tubule cells in the outer medulla, although
      oxidative stress increased by Alz or LuP might also be involved in renal
      carcinogenesis by MC.

PMID- 19167448
TI  - Effects of sulfur dioxide derivatives on expression of oncogenes and tumor
      suppressor genes in human bronchial epithelial cells.
AB  - Sulfur dioxide (SO(2)) is a major air pollutant suspected to act as a promoter or
      co-carcinogen. The present study was designed to investigate whether SO(2)
      derivatives (bisulfite and sulfite) had effects on the expression of several
      proto-oncogenes and tumor suppressor genes in cultured human bronchial epithelial
      (BEP2D) cells. The mRNA and protein levels were measured by real-time RT-PCR and
      western blotting, respectively, following exposure to differing SO(2)-derivative
      concentrations and exposure times. SO(2) derivatives caused mRNA and protein over
      expression of c-fos, c-jun, and c-myc at all tested doses (0.001-2mM). Over
      expression of H-ras and p53 were observed in cells receiving the highest
      concentration (0.1-2mM), as well as the under-expression of p16 and Rb. The over
      expression of c-fos and c-jun was observed after 24h recovery. The expression of
      c-myc and H-ras decreased to base line levels while the p53 expression decreased
      compared with control after 24h recovery. The mRNA and protein expression of p16
      and Rb remained at initial levels after 24h recovery. The data support the
      hypothesis that SO(2) derivatives could cause the activation of proto-oncogenes
      and inactivation of tumor suppressor genes and SO(2) derivatives may play a role
      in the pathogenesis of SO(2)-associated lung cancer.

PMID- 19167449
TI  - Evaluation of anti-oxidative, genotoxic and antigenotoxic potency of Codium
      tomentosum Stackhouse ethanolic extract in human lymphocytes in vitro.
AB  - The genome is constantly exposed to agents, both exogenous and endogenous, that
      damage DNA. Consequently, it is very important that determination of this agents
      and the protective agents. In this work, we evaluated the
      antigenotoxic/antimutagenic activity of the crude ethanolic extracts of Codium
      tomentosum Stackhouse (Chlorophyceae) (CTE), collected from The Coast of South
      East Marmara Sea, in human lymphocytes culture in vitro against
      genotoxic/mutagenic agents MMC, EMS and H(2)O(2) by using chromosome aberration
      (CA), sister chromatid exchange (SCE) and micronuclei (MN) assays as experimental
      endpoints. Also, in the present study, we determined total phenolic content and
      total antioxidant capacity (in soluble lipid and water). In addition, total
      protein, total carbohydrate, vitamins (A, C and E) and pigments (chlorophyll a,
      chlorophyll b and carotene) contents were also determined. Results of CA, SCE and
      MN tests show that CTEs have not shown genotoxic effect. In CTE plus MMC-, EMS-
      or H(2)O(2)- treated cultures, CA, SCE and MN frequency which induced by MMC, EMS
      or H(2)O(2) has been decreased significantly (p<0.05-0.001). This is the first
      report on genotoxicity/antigenotoxicity and anti-oxidative capacity of Codium
      tomentosum. Our results have clearly shown that CTE has strong anti-oxidative and
      antigenotoxic effect.

PMID- 19167450
TI  - Occurrence of aflatoxins in mahua (Madhuca indica Gmel.) seeds: synergistic
      effect of plant extracts on inhibition of Aspergillus flavus growth and aflatoxin
      production.
AB  - Occurrence of aflatoxin in Madhuca indica Gmel. seeds was determined by
      competitive ELISA. Eighty percent of mahua seed samples were found to be
      contaminated with aflatoxin. Total aflatoxin content ranged from 115.35 to
      400.54ppb whereas the concentration of AFB(1) was in the range of 86.43 to
      382.45ppb. Mahua oil was extracted by cold press expeller and analysed for
      contamination of aflatoxin in both the oil and cake samples. Total aflatoxin and
      aflatoxin B(1) were 220.66 and 201.57ppb in oil as compared to that in cake
      samples where it was 87.55 and 74.35ppb, respectively. Various individual and
      combined plant extracts were evaluated for their efficacy against growth of
      Aspergillus flavus and aflatoxin production in vitro. Combination of botanicals
      were found to be more effective in controlling fungal growth and aflatoxin
      production than individual extracts. Results of the present study suggests that
      synergistic effect of plant extracts can be used for control of fungal growth and
      aflatoxin production. These natural plant products may successfully replace
      synthetic chemicals and provide an alternative method to protect mahua as well as
      other agricultural commodities of nutritional significance from toxigenic fungi
      such as A. flavus and aflatoxin production.

PMID- 19167451
TI  - Hydroxyl radical generation dependent on extracellular ascorbate in rat striatum,
      as determined by microdialysis.
AB  - Ascorbate (AA), an antioxidant substance known as vitamin C, exists in the brain
      at a high concentration, although transfer into the brain after systemic
      administration of AA itself is limited. Intraperitoneal administration of
      dehydroascorbate (DHA) resulted in a rapid and progressive increase in
      extracellular AA in rat striatum in a dose-dependent manner. DHA administration
      increased 2,3- and 2,5-dihydroxybenzoate (2,3- and 2,5-DHBA) formation from
      salicylate in parallel with the increase in extracellular AA. Intrastriatal
      administration of active AA oxidase (AAO), but not the inactivated enzyme,
      completely suppressed the increase in 2,3- and 2,5-DHBA formation after the DHA
      administration. These findings suggest that extracellular AA might stimulate
      hydroxyl radical (OH) generation in the striatum. This is supported by the
      observation of dose-dependent OH generation upon intrastriatal administration of
      AA itself. In addition, deferoxamine, an iron chelator, decreased basal 2,3- and
      2,5-DHBA formation and strongly, though not completely, suppressed the DHA
      induced increase of 2,3- and 2,5-DHBA formation. Therefore, increased
      extracellular AA might function as a prooxidant and stimulate OH generation in
      cooperation with iron in rat striatum.

PMID- 19167452
TI  - Discrimination of a transformation phenotype in Syrian golden hamster embryo
      (SHE) cells using ATR-FTIR spectroscopy.
AB  - Primary Syrian hamster embryo (SHE) cells might be used to assess morphological
      transformation following treatment with chemical carcinogens. We employed
      attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy to
      interrogate SHE colonies, as complex biomolecules absorb in the mid-infrared (IR;
      lambda=2-20microm) giving vibrational spectra associated with structure and
      function. Early-passage SHE cells were cultured (pH 6.7) in the presence or
      absence of benzo[a]pyrene (B[a]P; 5.0microg/ml). Unstained colonies were applied
      to an ATR crystal, and vibrational spectra were obtained in the ATR mode using a
      Bruker Vector 22 FTIR spectrometer with Helios ATR attachment. These were
      individually baseline-corrected and normalised. Spectra were then analysed using
      principal component analysis (PCA) plus linear discriminant analysis (LDA). PCA
      was used to reduce the dataset dimensions before LDA was employed to reveal
      clustering. This determined whether wavenumber-absorbance relationships expressed
      as single points (scores) in 'hyperspace' might on the basis of multivariate
      distance reveal biophysical differences associated with morphologies in vehicle
      control (non-transformed or transformed) or carcinogen-treated (non-transformed
      or transformed) cells. Retrospectively designated SHE colonies (following
      staining and microscopic analysis) clustered according to whether they were
      vehicle control (non-transformed), B[a]P-treated (non-transformed) or transformed
      (control and B[a]P-treated). Scores plots pointed to a B[a]P-treated phenotype
      and derived loadings plots highlighted distinguishing markers in control
      transformed vs. B[a]P-treated transformed; these were mostly associated with
      Amide I, Amide II and phosphate stretching (asymmetric and symmetric) vibrations.
      Combined application of ATR-FTIR spectroscopy and unsupervised (PCA)/supervised
      (LDA) may be a novel approach to scoring SHE colonies for morphological
      transformation.

PMID- 19167453
TI  - Calcium/calmodulin signaling elicits release of cytochrome c during 2,3,7,8
      tetrachlorodibenzo-p-dioxin-induced apoptosis in the human lymphoblastic T-cell
      line, L-MAT.
AB  - We have reported previously that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      induces apoptosis in the human lymphoblastic T-cell line L-MAT, although these
      cells do not express the aromatic hydrocarbon receptor (AhR). The AhR-dependent
      pathway for the induction of immunotoxicity by TCDD has been studied extensively,
      but the AhR-independent pathway is not understood. Several studies have reported
      that TCDD elevates the concentration of free intracellular calcium ([Ca(2+)](i))
      in various types of cells. However, the precise mechanism of the increase in
      [Ca(2+)](i) that occurs during apoptosis induced by TCDD has not been elucidated.
      Upon treatment of L-MAT cells with 20nM TCDD, we observed an early increase in
      [Ca(2+)](i), within 30min of the addition of TCDD, which was followed by an
      additional increase at 90min, after which the increase in [Ca(2+)](i) was
      sustained until 3h after the addition of TCDD. A chelator of intracellular
      calcium, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
      tetra(acetoxymethyl ester) (BAPTA-AM), blocked the induction of apoptosis by TCDD
      in L-MAT cells, but EGTA, a chelator of extracellular calcium, did not. An
      antagonist of calcium-dependent calmodulin (CaM), W-7, inhibited the induction of
      apoptosis by TCDD in L-MAT cells. Moreover, W-7 suppressed the mitochondrial
      release of cytochrome c to the cytosol. These results demonstrate that activated
      Ca(2+)/CaM could transmit apoptotic signal(s) to mitochondria. The results
      suggest that Ca(2+)/CaM signals may play an important role in the induction of
      apoptosis in L-MAT cells by TCDD.

PMID- 19167454
TI  - Chlorpyrifos induces oxidative stress in oligodendrocyte progenitor cells.
AB  - There are increasing concerns regarding the relative safety of chlorpyrifos (CPF)
      to various facets of the environment. Although published works suggest that CPF
      is relatively safe in adult animals, recent evidence indicates that juveniles,
      both animals and humans, may be more sensitive to CPF toxicity than adults. In
      young animals, CPF is neurotoxic and mechanistically interferes with cellular
      replication and cellular differentiation, which culminates in the alteration of
      synaptic neurotransmission in neurons. However, the effects of CPF on glial cells
      are not fully elucidated. Here we report that chlorpyrifos is toxic to
      oligodendrocyte progenitors. In addition, CPF produced dose-dependent increases
      in 2',7'-dichlorodihydrofluorescein diacetate (H(2)DCF-DA) and dihydroethidium
      (DHE) fluorescence intensities relative to the vehicle control. Moreover, CPF
      toxicity is associated with nuclear condensation and elevation of caspase 3/7
      activity and Heme oxygenase-1 mRNA expression. Pan-caspase inhibitor QVDOPh and
      cholinergic receptor antagonists' atropine and mecamylamine failed to protect
      oligodendrocyte progenitors from CPF-induced injury. Finally, glutathione (GSH)
      depletion enhanced CPF-induced toxicity whereas nitric oxide synthetase inhibitor
      L-NAME partially protected progenitors and the non-specific antioxidant vitamin E
      (alpha-tocopherol) completely spared cells from injury. Collectively, this data
      suggests that CPF induced toxicity is independent of cholinergic stimulation and
      is most likely caused by the induction of oxidative stress.

PMID- 19167455
TI  - Involvement of caspases and transmembrane metalloproteases in sulphur mustard
      induced microvesication in adult human skin in organ culture: directions for
      therapy.
AB  - While skin is a major target for sulphur mustard (HD), a therapy to limit HD
      induced vesication is currently not available. Since it is supposed that
      apoptotic cell death and proteolytic digestion of extracellular matrix proteins
      by metalloproteases are initiating factors for blister formation, we have
      explored whether inhibition of these processes could prevent HD-induced epidermal
      dermal separation using adult human skin in organ culture. Involvement of the
      caspase and the metalloprotease families was confirmed by the observation that
      their respective broad spectrum inhibitors, Z-VAD-fmk and GM6001, each suppressed
      HD-induced microvesication. The lowest effective concentrations were 10 and
      100microM, respectively. Using specific inhibitors for caspase-8 (> or =10microM)
      and caspase-9 (> or =10microM) we learned that HD-induced apoptosis is initiated
      by the death receptor pathway as well as by the mitochondrial pathway.
      Remarkably, blocking caspase-8 activity resulted in morphologically better
      conserved cells than blocking caspase-9 activity. We zoomed in on the role of
      metalloproteases in HD-induced microvesication by testing the effects of two
      inhibitors: dec-RVKR-cmk and TAPI-2. Dec-RVKR-cmk is an inhibitor of furin, which
      activates transmembrane enzymes of the 'a disintegrin and metalloproteinase'
      (ADAM)-family as well as the membrane-type metalloproteases (MTx-MMP). TAPI-2
      specifically inhibits TNFalpha-converting enzyme (TACE/ADAM17), which is involved
      in pericellular proteolysis. Both inhibitors prevented microvesication at
      concentrations of > or =500 and > or =20microM, respectively. This confirms that
      ADAMs and MT-MMPs play a role in HD-induced epidermal-dermal separation, with a
      particular role for TACE/ADAM17. Since TACE is involved not only in degradation
      of cell-matrix adhesion structures, but also in ectodomain shedding of ligands
      for epidermal growth factor receptor (EGFR) and in release of TNFalpha, these
      results imply TACE-mediated pathways as a new concept in HD toxicity. In
      conclusion, transmembrane metalloproteases probably form a main target for
      treatment of blisters in HD casualties. The observation that microvesication in
      the ex vivo human skin model still could be prevented when the metalloprotease
      inhibitor GM6001 was applied up to 8h after exposure to HD opens perspectives for
      non-urgent cure of HD casualties.

PMID- 19167456
TI  - 15-Deoxy-Delta(12,14)-prostaglandin J(2) induces mitochondrial-dependent
      apoptosis through inhibition of PKA/NF-kappaB in renal proximal epithelial cells.
AB  - We have previously reported the cyclopentenone prostaglandin 15-deoxy
      Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) induces renal proximal epithelial
      cell death through NF-kappaB inhibition. However, the upstream and down-stream
      signaling pathways that NF-kappaB inhibition mediates 15d-PGJ(2)-induced
      apoptosis remain to be defined. In the present study, we determined whether NF
      kappaB inhibition induces cell death through the mitochondrial apoptotic pathway
      and whether protein kinase A (PKA) functions upstream of NF-kappaB inhibition by
      15d-PGJ(2). The role of NF-kappaB inhibition in this apoptotic pathway was
      evaluated using NF-kappaB p65 transfected cells. 15d-PGJ(2) induced cell death by
      a PPARgamma-independent mechanism and the cell death was prevented by NF-kappaB
      p65 transfection. 15d-PGJ(2) treatment caused disruption of mitochondrial
      membrane potential, cytochrome c release, and caspase-3 activation, suggesting
      that 15d-PGJ(2) induces cell death through a mitochondria-dependent apoptotic
      mechanism. These changes by 15d-PGJ(2) were attenuated by NF-kappaB p65
      transfection. 15d-PGJ(2) treatment resulted in an increase in Bax expression,
      which were blocked by NF-kappaB p65 transfection. 15d-PGJ(2) treatment caused PKA
      inhibition and 15d-PGJ(2)-induced cell death was enhanced by the PKA specific
      inhibitor H89. Inhibition of NF-kappaB by 15d-PGJ(2) was prevented by addition of
      forskolin, a PKA activator. Taken together, these results suggest that PKA
      dependent NF-kappaB inhibition stimulates 15d-PGJ(2)-mediated mitochondrial
      apoptotic pathway through alterations in expression of the NF-kappaB target genes
      Bax.

PMID- 19167457
TI  - Gene expression profiles in rat lung after inhalation exposure to C60 fullerene
      particles.
AB  - Concern over the influence of nanoparticles on human health has risen due to
      advances in the development of nanotechnology. We are interested in the influence
      of nanoparticles on the pulmonary system at a molecular level. In this study,
      gene expression profiling of the rat lung after whole-body inhalation exposure to
      C(60) fullerene (0.12mg/m(3); 4.1x10(4) particles/cm(3), 96nm diameter) and
      ultrafine nickel oxide (Uf-NiO) particles (0.2mg/m(3); 9.2x10(4) particles/cm(3),
      59nm diameter) as a positive control were employed to gain insights into these
      molecular events. In response to C(60) fullerene exposure for 6h a day, for 4
      weeks (5 days a week), C(60) fullerene particles were located in alveolar
      epithelial cells at 3 days post-exposure and engulfed by macrophages at both 3
      days and 1 month post-exposures. Gene expression profiles revealed that few genes
      involved in the inflammatory response, oxidative stress, apoptosis, and
      metalloendopeptidase activity were up-regulated at both 3 days and 1 month post
      exposure. Only some genes associated with the immune system process, including
      major histocompatibility complex (MHC)-mediated immunity were up-regulated. These
      results were significantly different from those of Uf-NiO particles which induced
      high expression of genes associated with chemokines, oxidative stress, and matrix
      metalloproteinase 12 (Mmp12), suggesting that Uf-NiO particles lead to acute
      inflammation for the inhalation exposure period, and the damaged tissues were
      repaired in the post-exposure period. We suggest that C(60) fullerene might not
      have a severe pulmonary toxicity under the inhalation exposure condition.

PMID- 19167458
TI  - Involvement of glycans in the immunological cross-reaction between alpha
      macroglobulin and hemocyanin of the gastropod Helix pomatia.
AB  - By tandem-crossed immunoelectrophoresis and ELISA experiments an immunological
      relationship was observed between alpha-macroglobulin (alphaM) and hemocyanin
      (Hc) of the terrestrial snail Helix pomatia. Both glycoproteins occur in the
      hemolymph: alphaM (minor component) as a specific proteinase inhibitor, Hc
      (consisting of three components: alpha(D)-HpH, alpha(N)-HpH and beta-HpH) as
      oxygen transport protein. The cross-reaction was found to be correlated with
      glycosylation. (i) With beta-HpH, which is richer in carbohydrates than alpha(D)
      HpH and alpha(N)-HpH, mainly due to a higher 3-O-methyl-d-galactose content, the
      cross-reaction with HpalphaM was highest. (ii) From the 8 functional units,
      designated a-h, isolated from beta-HpH, two that lack carbohydrates (c and f)
      were not recognized by antibodies against HpalphaM, while the six glycosylated
      ones were strongly cross-reacting. The nearly complete loss of the cross
      reactivity upon deglycosylation of functional units d and g and the inhibition in
      competitive ELISA experiments by glycopeptides isolated from both beta-HpH and
      HpalphaM are further evidence that glycans are involved in the immunological
      relationship between HpH and HpalphaM. Carbohydrate analyses indicated that the
      glycan structures present on HpalphaM are very similar (or identical) to those
      found on HpH, suggesting that glycans are common epitopes on both proteins.
      Especially d-xylose and 3-O-methyl-d-galactose seem to be responsible for the
      cross-reactivity since the alpha-macroglobulin and hemocyanin of the cephalopod
      Sepia officinalis, which lack these two monosaccharides in their glycan
      structures, do not immunologically cross-react.

PMID- 19167459
TI  - Apoptosis signaling proteins as prognostic biomarkers in colorectal cancer: a
      review.
AB  - Colorectal cancer is a leading cause of cancer related mortality in the Western
      world. In recent years, combination 5-fluorouracil based adjuvant chemotherapy as
      first line treatment of this disease has led to improved disease free and overall
      survival. However drug resistance, both innate and acquired, remains an obstacle
      in the effective treatment of this disease. Apoptotic pathways are frequently
      altered in both tumor progression and drug resistance; therefore proteins
      associated with this pathway may have potential as prognostic biomarkers for this
      disease. Identification of clinical biomarkers that are able to identify patients
      who are more likely to respond to specific chemotherapy will lead to more
      personalized, effective, and less toxic therapy. This review focuses on the
      current status of apoptosis related proteins as biomarkers for colorectal cancer
      and discusses the possible application of systems approaches in this context.

PMID- 19167460
TI  - Human cancer cell lines: Experimental models for cancer cells in situ? For cancer
      stem cells?
AB  - Established human cancer cell lines are routinely used as experimental models for
      human cancers. Their validity for such use is analyzed and discussed, with
      particular focus on thyroid tumors. Although cell lines retain some properties of
      the cells of origin, from the points of view of their genetics, epigenetics and
      gene expression, they show clear differences in these properties compared to in
      vivo tumors. This can be explained by a prior selection of initiating cells and a
      Darwinian evolution in vitro. The properties of the cell lines are compared to
      those of the postulated cancer stem cells and their use as models in this regard
      are discussed. Furthermore, other proper and possible uses of the cell lines are
      discussed.

PMID- 19167461
TI  - Site-specific regulation of CA(V)2.2 channels by protein kinase C isozymes betaII
      and epsilon.
AB  - Ca(v)2.2 high voltage-gated calcium channels are regulated by phorbol-12
      myristae, 13-acetate (PMA) via Ser/Thr protein kinase C (PKC) phosphorylation
      sites in the I-II linker and C-terminus of the alpha(1) 2.2 subunit. Here we show
      that PMA enhancement of Ca(v)2.2 currents expressed in Xenopus oocytes can be
      blocked by inhibitors of PKC betaII or PKC epsilon isozymes, as shown previously
      for Ca(v)2.3 currents, and that microinjection of PKC betaII or PKC epsilon
      isozymes in the oocytes expressing the WT Ca(v)2.2 channels increases the basal
      barium current (I(Ba)). The I-V plot shows a large increase in current amplitude
      with PKC betaII and PKC epsilon isozymes with only a small shift in the peak
      I(Ba) in the hyperpolarizing direction. The potentiation of Ca(v)2.2 currents by
      microinjection of PKC betaII and PKC epsilon isozymes was not altered by the
      inhibition of G proteins with GDPbetaS. The combination of isozyme specific
      inhibitors with previously generated Ser/Thr to Ala mutants of alpha(1) 2.2
      subunit revealed that PKC betaII or PKC epsilon isozymes (but not PKC alpha or
      delta) can provide full enhancement through the stimulatory site (Thr-422) in the
      I-II linker but that PKC epsilon is better at decreasing channel activity through
      the inhibitory site Ser-425. The enhancing effect of PKC betaII or epsilon at Thr
      422 is dominant over the inhibitory effect at Ser-425. Injected PKC betaII also
      enhances Ca(v)2.2 current when any of the potential stimulatory sites (Ser-1757,
      Ser-2108 and Ser-2132) are available in the C-terminus. PKC epsilon provides
      lesser enhancement with C-terminal sites and only with Ser-2108 and Ser-2132.
      Sites Ser-1757 and Ser-2132, but not Ser-2108, are dominant over the inhibitory
      site Ser-425. Collectively, these results reveal a hierarchy of regulatory sites
      in Ca(v)2.2 channels. Site-specific regulation by different PKC isozymes may
      allow graded levels of channel activation and susceptibility or resistance to
      subsequent stimulatory events.

PMID- 19167462
TI  - Persistent working memory dysfunction following traumatic brain injury: evidence
      for a time-dependent mechanism.
AB  - The prefrontal cortex is highly vulnerable to traumatic brain injury (TBI)
      resulting in the dysfunction of many high-level cognitive and executive functions
      such as planning, information processing speed, language, memory, attention, and
      perception. All of these processes require some degree of working memory.
      Interestingly, in many cases, post-injury working memory deficits can arise in
      the absence of overt damage to the prefrontal cortex. Recently, excess GABA
      mediated inhibition of prefrontal neuronal activity has been identified as a
      contributor to working memory dysfunction within the first month following
      cortical impact injury of rats. However, it has not been examined if these
      working memory deficits persist, and if so, whether they remain amenable to
      treatment by GABA antagonism. Our findings show that working memory dysfunction,
      assessed using both the delay match-to-place and delayed alternation T-maze
      tasks, following lateral cortical impact injury persists for at least 16 weeks
      post-injury. These deficits were found to be no longer the direct result of
      excess GABA-mediated inhibition of medial prefrontal cortex neuronal activity.
      Golgi staining of prelimbic pyramidal neurons revealed that TBI causes a
      significant shortening of layers V/VI basal dendrite arbors by 4 months post
      injury, as well as an increase in the density of both basal and apical spines in
      these neurons. These changes were not observed in animals 14 days post-injury, a
      time point at which administration of GABA receptor antagonists improves working
      memory function. Taken together, the present findings, along with previously
      published reports, suggest that temporal considerations must be taken into
      account when designing mechanism-based therapies to improve working memory
      function in TBI patients.

PMID- 19167463
TI  - Neuronal nitric oxide synthase activation is involved in insulin-mediated
      cardiovascular effects in the nucleus tractus solitarii of rats.
AB  - Neuronal nitric oxide synthases (nNOS) is distributed throughout the central
      nervous system (CNS) and has been proposed to modulate neuronal activity in the
      nucleus tractus solitarii (NTS). Here, we investigated whether the activation of
      nNOS is involved in insulin-induced cardiovascular responses in the NTS. Insulin
      (100 IU/ml) was unilaterally microinjected into the NTS, and the cardiovascular
      effects were evaluated before and after microinjection of the nNOS inhibitors 7
      nitroindazole (7-NI) (5 pmol) and N(5)-(1-imino-3-butenyl)-l-ornithine (vinyl-L
      NIO) (600 pmol). Western blot and immunohistochemical analyses were performed to
      determine nNOS phosphorylation levels after insulin or phosphoinositide 3-kinase
      (PI3K) inhibitor LY294002 microinjection into the NTS. Unilateral microinjection
      of insulin into the NTS produced prominent depressor and bradycardic effects in
      WKY rats. Pretreatment with the nNOS inhibitors 7-NI and Vinyl-L-NIO attenuated
      the cardiovascular response evoked by insulin in Wistar-Kyoto (WKY) rats.
      Moreover, Western blot analysis showed a significant increase in nNOS (16.5+/-0.4
      fold; P<0.05; n=4) phosphorylation after insulin injection, whereas the PI3K
      inhibitor LY294002 abolished the insulin-induced effects. In situ nNOS
      phosphorylation was found to be increased in the NTS after insulin injection.
      Furthermore, co-immunoprecipitation assay showed Akt and nNOS can bind to each
      other as detected by phospho-Akt(S473) and phospho-nNOS(S1416) antibodies. In
      vitro kinase assay showed insulin activated Akt can directly phosphorylate
      nNOS(S1416). These results demonstrated that nNOS may couple with the activation
      of the insulin receptor, via the liberation of NO, in order to participate in
      central cardiovascular regulation of WKY rats.

PMID- 19167464
TI  - Enhancement of inhibitory synaptic transmission in large aspiny neurons after
      transient cerebral ischemia.
AB  - Large aspiny neurons and most of the GABAergic interneurons survive transient
      cerebral ischemia while medium spiny neurons degenerate in 24 h. Expression of a
      long-term enhancement of excitatory transmission in medium spiny neurons but not
      in large aspiny neurons has been indicated to contribute to this selective
      vulnerability. Because neuronal excitability is determined by the counterbalance
      of excitation and inhibition, the present study examined inhibitory synaptic
      transmission in large aspiny neurons after ischemia in rats. Transient cerebral
      ischemia was induced for 22 min using the four-vessel occlusion method and whole
      cell voltage-clamp recording was performed on striatal slices. The amplitudes of
      evoked inhibitory postsynaptic currents in large aspiny neurons were
      significantly increased at 3 and 24 h after ischemia, which was mediated by the
      increase of presynaptic release. Postsynaptic responses were depressed at 24 h
      after ischemia. Inhibitory postsynaptic currents could be evoked in large aspiny
      neurons at 24 h after ischemia, suggesting that they receive GABAergic inputs
      from the survived GABAergic interneurons. Muscimol, a GABA(A) receptor agonist,
      presynaptically facilitated inhibitory synaptic transmission at 24 h after
      ischemia. Such facilitation was dependent on the extracellular calcium and
      voltage-gated sodium channels. The present study demonstrates an enhancement of
      inhibitory synaptic transmission in large aspiny neurons after ischemia, which
      might reduce excitotoxicity and contribute, at least in part, to the survival of
      large aspiny neurons. Our data also suggest that large aspiny neurons might
      receive inhibitory inputs from GABAergic interneurons.

PMID- 19167465
TI  - NaCl responsive taste cells in the mouse fungiform taste buds.
AB  - Previous studies have demonstrated that rodents' chorda tympani (CT) nerve fibers
      responding to NaCl can be classified according to their sensitivities to the
      epithelial sodium channel (ENaC) blocker amiloride into two groups: amiloride
      sensitive (AS) and -insensitive (AI). The AS fibers were shown to respond
      specifically to NaCl, whereas AI fibers broadly respond to various electrolytes,
      including NaCl. These data suggest that salt taste transduction in taste cells
      may be composed of at least two different systems; AS and AI ones. To further
      address this issue, we investigated the responses to NaCl, KCl and HCl and the
      amiloride sensitivity of mouse fungiform papilla taste bud cells which are
      innervated by the CT nerve. Comparable with the CT data, the results indicated
      that 56 NaCl-responsive cells tested were classified into two groups; 25 cells (
      approximately 44%) narrowly responded to NaCl and their NaCl response were
      inhibited by amiloride (AS cells), whereas the remaining 31 cells ( approximately
      56%) responded not only to NaCl, but to KCl and/or HCl and showed no amiloride
      inhibition of NaCl responses (AI cells). Amiloride applied to the basolateral
      side of taste cells had no effect on NaCl responses in the AS and AI cells.
      Single cell reverse transcription-polymerase chain reaction (RT-PCR) experiments
      indicated that ENaC subunit mRNA was expressed in a subset of AS cells. These
      findings suggest that the mouse fungiform taste bud is composed of AS and AI
      cells that can transmit taste information differently to their corresponding
      types of CT fibers, and apical ENaCs may be involved in the NaCl responses of AS
      cells.

PMID- 19167466
TI  - Dependence of monocyte chemoattractant protein 1 induced hyperalgesia on the
      isolectin B4-binding protein versican.
AB  - The type 1 chemokine monocyte chemoattractant protein (MCP-1) has been implicated
      in the generation of inflammatory and neuropathic pain, but the underlying
      mechanism remains poorly understood. Here we show that mechanical hyperalgesia
      induced by intradermal injection of MCP-1 in the rat is blocked by the
      intrathecal administration of isolectin B4 (IB4)-saporin, a selective neurotoxin
      for IB4(+)/Ret(+)-nociceptors. MCP-1-induced hyperalgesia is also attenuated by
      intrathecal antisense oligodeoxynucleotides targeting mRNA for versican, a
      molecule that binds MCP-1 and that also renders the Ret-expressing nociceptors
      IB4-positive (+). Finally, peripheral administration of ADAMTS-4 or
      chondroitinase ABC, two enzymes that disrupt versican integrity by the
      degradation of the versican core-protein or its chondroitin sulfate
      glycosaminoglycan side chains, respectively, also attenuated MCP-1 hyperalgesia
      at the site of nociceptive testing. We suggest that versican's glycosaminoglycan
      side chains present MCP-1 to a CCR2 expressing cell type in the skin that, in
      turn, selectively activates IB4(+)/Ret(+) nociceptors, thereby contributing to
      enhanced mechanical sensitivity under inflammatory conditions.

PMID- 19167467
TI  - Asymmetric expression patterns of brain transthyretin in normal mice and a
      transgenic mouse model of Alzheimer's disease.
AB  - Brain asymmetry is linked with several neurological diseases, and transthyretin
      (TTR) is a protein sequestering beta-amyloid (Abeta) and helping to prevent the
      Alzheimer's disease (AD). We show, by real time reverse transcription-polymerase
      chain reaction (RT-PCR), in situ hybridization and Western blotting, that TTR
      exhibits a pattern of adult male-specific, leftward distribution in the mouse
      brain. This asymmetry appeared to be mainly due to the asymmetric distribution of
      the choroid plexus cells in the ventricles. Unlike the normal mice, however, the
      hemispheric levels of TTR transcripts of 2- and 6-month-old Tg2576 mice, a
      transgenic AD mouse model overexpressing Abeta, were symmetric in both sexes.
      Furthermore, at the age of 10 months when the pathological AD-like features had
      developed, the level of TTR transcripts in the left hemisphere of the male Tg2576
      became significantly lower than the right one. This lowering of TTR transcript is
      accompanied with a higher Abeta level in the left hemisphere of the 10-month
      Tg2576 males. Finally, for both genders, the TTR transcript levels in the two
      hemispheres of aged Tg2576 mice were lower than either the adult Tg2576 or the
      aged nontransgenic controls. Based on the above, we suggest scenarios to
      correlate the changes in the levels and hemispheric patterns of TTR expression to
      the pathogenesis of AD.

PMID- 19167468
TI  - A putatively novel form of spontaneous coordination in neural activity.
AB  - We simultaneously recorded local field potentials from three sites along the
      olfactory-entorhinal axis in rats lightly anesthetized with isoflurane, as part
      of another experiment. While analyzing the initial data from that experiment with
      spectrograms, we discovered a potentially novel form of correlated neural
      activity, with near-simultaneous occurrence across the three widely separated
      brain sites. After validating their existence further, we named these events
      Synchronous Frequency Bursts (SFBs). Here we report our initial investigations
      into their properties and their potential functional significance. In Experiment
      1, we found that SFBs have highly regular properties, consisting of brief
      (approximately 250 ms), high amplitude bursts of LFP energy spanning frequency
      ranges from the delta band (1-4 Hz) to at least the low gamma band (30-50 Hz).
      SFBs occurred almost simultaneously across recording sites, usually with onsets
      <25 ms apart, and there was no clear pattern of temporal leading or lagging among
      the sites. While the SFBs had fairly typical, exponentially decaying power
      spectral density plots, their coherence structure was unusual, with high peaks in
      several narrow frequency ranges and little coherence in other bands. In
      Experiment 2, we found that SFBs occurred far more often under light anesthesia
      than deeper anesthetic states, and were especially prevalent as the animals
      regained consciousness. Finally, in Experiment 3 we showed that SFBs occur
      simultaneously at a significant rate across brain sites from putatively different
      functional subsystems--olfactory versus motor pathways. We suggest that SFBs do
      not carry information per se, but rather, play a role in coordinating activity in
      different frequency bands, potentially brain-wide, as animals progress from sleep
      or anesthesia toward full consciousness.

PMID- 19167469
TI  - Three drimane sesquiterpene glucoside from the aerial parts of Dryopteris
      fragrans (L.) schot.
AB  - Sesquiterpene glucoside was isolated from the aqueous extract of the aerial parts
      of Dryopteris fragrans (L.) schot. Three new sesquiterpene glucoside
      xianglinmaojuesides A-C (1-3), 3beta,11-dihydroxy-drim-8 (12)-en-11-O-beta-D
      glucopyranoside (1), 3beta,11-dihydroxy-drim-8(12)-en-3-O-beta-D-glucopyranoside
      (2), and 11,14-dihydroxy-drim-8(12)-en-11-O-beta-D-glucopyranoside (3) were
      finally obtained by reversed-phase HPLC and their structures were elucidated by
      HRESIMS and 1D, 2D NMR analyses.

PMID- 19167470
TI  - Effects of in utero arsenic exposure on child immunity and morbidity in rural
      Bangladesh.
AB  - Chronic exposure to arsenic, a potent carcinogen and toxicant, via drinking water
      is a worldwide public health problem. Because little is known about early-life
      effects of arsenic on immunity, we evaluated the impact of in utero exposure on
      infant immune parameters and morbidity in a pilot study. Pregnant women were
      enrolled at 6-10 weeks of gestation in Matlab, a rural area of Bangladesh,
      extensively affected by arsenic contamination of tubewell water. Women (n=140)
      delivering at local clinics were included in the study. Anthropometry and
      morbidity data of the pregnant women and their children, as well as infant thymic
      size by sonography were collected. Maternal urine and breast milk were collected
      for immune marker and arsenic assessment. Maternal urinary arsenic during
      pregnancy showed significant negative correlation with interleukin-7 (IL-7) and
      lactoferrin (Ltf) in breast milk and child thymic index (TI). Urinary arsenic was
      also positively associated with fever and diarrhea during pregnancy and acute
      respiratory infections (ARI) in the infants. The effect of arsenic exposure on
      ARI was only evident in male children. The findings suggest that in utero arsenic
      exposure impaired child thymic development and enhanced morbidity, probably via
      immunosuppression. The effect seemed to be partially gender dependent. Arsenic
      exposure also affected breast milk content of trophic factors and maternal
      morbidity.

PMID- 19167471
TI  - Differential induction of cytochrome P450 1A1 and 1B1 mRNA in primary cultured
      bovine hepatocytes treated with TCDD, PBDD/Fs and feed ingredients.
AB  - This study investigates the dose-dependent expression of CYP1A1 and CYP1B1 in
      primary cultured bovine hepatocytes exposed to TCDD, several polybrominated
      dibenzo-p-dioxins and furans (PBDD/Fs) congeners and fish oil used as animal feed
      ingredients to identify their dioxin-like potentials. Hepatocytes were isolated
      from calf liver, cultured and treated for 24h with the target compounds or
      extracts. Quantitative real time polymerase chain reaction analysis (qRT-PCR)
      showed that relative mRNA levels for CYP1A1 and CYP1B1 exhibited a dose-dependent
      induction by TCDD. The EC(50) of the TCDD concentration for CYP1A1 expression was
      approximately 4-fold less than that of CYP1B1. The estimated dioxin-like toxic
      potential of PBDD/Fs could be ranked in the following order: 2,3,7,8
      TBDD>1,2,3,7,8-PBDF>2,3,4,7,8-PBDF>1,2,3,6,7,8-HBDD. A good correlation was also
      observed in HRGC/HRMS-derived TEQs in fish oil samples and relative CYP1A1 mRNA
      induction in bovine hepatocytes treated with purified fish oil extracts. The data
      suggested that quantification of biomarker regulations in primary cultured
      hepatocytes could represent an effective tool for both the screening and study of
      various chemical entities in larger animals.

PMID- 19167472
TI  - Chromium VI administration induces oxidative stress in hypothalamus and anterior
      pituitary gland from male rats.
AB  - Hexavalent chromium (Cr VI)-containing compounds are known carcinogens which are
      present in industrial settings and in the environment. The major route of
      chromium exposure for the general population is oral intake. Previously we have
      observed that Cr VI affects anterior pituitary secretion and causes oxidative
      stress in vitro. The aim of the present work was to investigate if in vivo Cr VI
      treatment (100 ppm of Cr VI in drinking water for up 30 days) causes oxidative
      stress in hypothalamus and anterior pituitary gland from male rats. This
      treatment produced a 4-fold increase of chromium content in hypothalamus and 10
      fold increase in anterior pituitary gland. Lipid peroxidation showed a
      significant increase in hypothalamus and anterior pituitary. Cr VI augmented
      superoxide dismutase activity in anterior pituitary gland and glutathione
      reductase activity in hypothalamus, but glutathione peroxidase and catalase
      activities remained unchanged in both tissues. Heme oxygenase-1 mRNA expression
      significantly rose in both tissues. Metallothionein 1 mRNA content increased in
      anterior pituitary and metallothionein 3 mRNA increased in hypothalamus. These
      results show, for the first time, that oral chronic administration of Cr VI
      produces oxidative stress on the hypothalamus and anterior pituitary gland which
      may affect normal endocrine function.

PMID- 19167473
TI  - Decreased aortic contractile reaction to 5-hydroxytryptamine in rats with long
      term hypertension induced by lead (Pb(2+)) exposure.
AB  - Male Wistar rats were exposed to 100ppm Pb(2+) in drinking water for 10 months.
      Tail blood pressure, serum 5-hydroxytryptamine (5-HT), the expression of 5-HT(2B)
      receptor in the aorta, the aortic response to 5-HT, and the pathologic changes of
      aorta were examined. The systolic blood pressure of Pb(2+) exposed group was
      significantly increased after 2 months of Pb(2+) exposure. After 10 months of
      Pb(2+) exposure, aortic contractile response to 5-HT was significantly decreased.
      There was no significant difference in the levels of serum 5-HT and the
      expression of 5-HT(2B) receptor between these two groups. The aortic media and
      the media-lumen ratio of Pb(2+) exposed group were significantly increased. These
      data suggest that long-term Pb(2+) exposure can increase blood pressure, and can
      alter the function and structure of aortic of rats. The decreased aortic response
      to 5-HT has little relation to the expression of 5-HT(2B) receptor and the serum
      level of 5-HT, maybe is a result of the aortic structural alteration.

PMID- 19167474
TI  - The herbicide linuron reduces testosterone production from the fetal rat testis
      during both in utero and in vitro exposures.
AB  - In utero exposure to linuron, an urea-based herbicide, results in a pattern of
      malformations of androgen-dependent tissues in adult male rat offspring
      resembling that produced by some phthalate esters which are known to decrease
      fetal testosterone production. This study investigated the impact of in utero
      linuron treatment on fetal testis gene expression and testosterone production.
      Timed-pregnant Sprague Dawley rats were administered corn oil vehicle, 12.5, 25,
      50 or 75mg linuron/day/kg orally from GD13 to 18. Ex vivo testosterone (T)
      production was significantly decreased at 50 and 75mg/kg when analyzed on a per
      litter basis. Unlike the phthalate esters, linuron treatment did not affect
      insl3, cyp17a, cyp11a or StAR mRNA expression. Control GD18 fetal testes were
      then incubated with increasing concentrations of linuron (1-300microM) to
      evaluate if linuron inhibited T production in vitro. T production was
      significantly reduced at 30microM and above. Progesterone production was not
      affected in any of the studies indicating that linuron directly inhibited
      testosterone production in the absence of cytotoxicity. These results indicate
      the malformations induced by linuron and phthalate esters in male offspring are
      similar because both reduce fetal T levels during the critical period of sex
      differentiation but suggest that the mechanisms differ.

PMID- 19167475
TI  - A novel powder sample holder for the determination of glass transition
      temperatures by DMA.
AB  - The use of a new sample holder for dynamic mechanical analysis (DMA) as a means
      to characterise the Tg of powdered hydroxypropyl methyl cellulose (HPMC) has been
      investigated. A sample holder was constructed consisting of a rectangular
      stainless steel container and a lid engineered to fit exactly within the walls of
      the container when clamped within a TA instruments Q800 DMA in dual cantilever
      configuration. Physical mixtures of HPMC (E4M) and aluminium oxide powders were
      placed in the holder and subjected to oscillating strains (1 Hz, 10 Hz and 100
      Hz) whilst heated at 3 degrees C/min. The storage and loss modulus signals showed
      a large reduction in the mechanical strength above 150 degrees C which was
      attributed to a glass transition. Optimal experimental parameters were determined
      using a design of experiment procedure and by analysing the frequency dependence
      of Tg in Arrhenius plots. The parameters were a clamping pressure of 62 kPa, a
      mass ratio of 0.2 HPMC in aluminium oxide, and a loading mass of either 120 mg or
      180 mg. At 1 Hz, a Tg of 177+/-1.2 degrees C (n=6) for powdered HPMC was
      obtained. In conclusion, the new powder holder was capable of measuring the Tg of
      pharmaceutical powders and a simple optimization protocol was established, useful
      in further applications of the DMA powder holder.

PMID- 19167476
TI  - Enhancement of radiotherapeutic effectiveness by temperature-sensitive liposomal
      1-methylxanthine.
AB  - Most of methylxanthine derivatives including caffeine have been known to
      radiosensitize cancer cells, but the obstacles such as toxicity, request of high
      dose and poor solubility hinder their preclinical evaluations and clinical
      applications. In this study, we evaluated the efficacy of 1-methylxanthine (1
      MTX), a caffeine metabolite as a radiosensitizer and the in vivo effectiveness of
      the temperature-sensitive liposomal 1-methylxanthine (tsl-MTX) in combination
      with ionizing radiation and regional hyperthermia. In human colorectal and lung
      cancer cells, treatment of 1-MTX sensitized cells to ionizing radiation. To
      evaluate the in vivo capability of 1-MTX to radiosensitize tumors, we developed
      temperature-sensitive liposomal 1-MTX using DPPC:DMPC:DSPC (4:1:1 molar ratio)
      with intention of overcoming lethal toxicity of 1-MTX and controlling drug
      release. The particle size of the liposomes was approximately 200 nm in diameter.
      The release of 1-MTX from the liposomes was responding to increase of
      temperature. In xenograft tumor-bearing mice, the tsl-MTX administered using the
      i.p. route showed delay of tumor growth. Importantly, tsl-MTX in combination with
      radiation and regional hyperthermia exhibited marked delay of tumor growth,
      suggesting that 1-MTX effectively enhanced radiation-induced suppression of tumor
      growth. In conclusion, tsl-MTX has highly efficacious anticancer competence in
      vivo, enhancing radiotherapeutic effectiveness, and feasibility for further
      clinical applications.

PMID- 19167477
TI  - Age related and hypothyroidism related changes on the stoichiometry of
      neurofilament subunits in the developing rat brain.
AB  - Hypothyroidism in the developing brain results in progressive intraneuronal
      accumulation of neurofilament (NF) proteins in the proximal hillock regions of
      axons, analogous to the pathological intraneuronal accumulation of NF in common
      neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and
      Amyotrophic lateral sclerosis. A preferential decline in the expression of the
      light chain of NF occurs in all the three diseases leading to an absolute change
      in stoichiometry of the NF subunits. Using the developing hypothyroid rat cerebra
      as a model, we have tried to elucidate if age or hypothyroidism causes a change
      in the stoichiometry or molar ratio of the NF subunits which could be responsible
      for their aberrant intraneuronal accumulation. Western blotting and
      chemiluminescence assay of cytoskeletal preparations from normal and hypothyroid
      developing rats at postnatal days 5 (PND5), PND15 and PND25 shows that in the
      normal cerebra, the expression of NFL and NFM were abundant during the first 2
      weeks, corresponding to the onset of axonal outgrowth and synaptogenesis, whereas
      that of NFH was predominant during the second and third weeks corresponding to
      the period of maturation of synapses, axonal caliber and transport processes.
      These results show that consistent with the requirement for neuronal
      differentiation during synaptogenesis, the molar ratios NFH:NFM:NFL changed
      significantly from 1:3:9 at PND5 to 1:2:6 at PND25. Hypothyroidism caused a 40
      60% decline in the expression of all three subunits. However, at all three ages
      examined, differences in the molar ratios of the NF subunits between normal and
      hypothyroid cerebra were insignificant suggesting that factors other than
      alteration in the stoichiometry of NF subunits are associated with their aberrant
      intraneuronal aggregation.

PMID- 19167479
TI  - Vibrio vulnificus cytolysin induces apoptosis in HUVEC, SGC-7901 and SMMC-7721
      cells via caspase-9/3-dependent pathway.
AB  - Vibrio vulnificus cytolysin (VVC) is known to be a pore-forming toxin which shows
      cytotoxicity for mammalian cells in culture and induces apoptosis in endothelial
      cells. In order to determine whether VVC induces apoptosis in vascular
      endothelial cells and tumor cells, the cytotoxicity induced by recombinant VVC
      (rVVC) and its potential mechanism in HUVEC, SGC-7901 and SMMC-7721 cells were
      investigated. Our study demonstrated that rVVC induced the release of
      intracellular K(+) from all the target cells, yet lactate dehydrogenase was not
      released by rVVC. It indicates that osmotic lysis might not contribute to the
      cytolysin-induced cytotoxicity. The study also demonstrated that rVVC induced
      apoptosis in HUVEC, SGC-7901 and SMMC-7721 cells in time- and dosage-dependent
      manners, which was associated with the activation of caspase-9 and -3, but not
      caspase-8. During the apoptotic process of the target cells, rVVC labeled with
      FITC was monitored to attach initially to the surface of the cells and entered
      the cytoplasma subsequently. These findings suggest that VVC may be not only a
      pore-forming toxin, but also a transmembrane toxin with powerful ability to
      induce apoptosis in human vascular endothelial cells and tumor cells.

PMID- 19167478
TI  - Chronic nicotine alters cannabinoid-mediated locomotor activity and receptor
      density in periadolescent but not adult male rats.
AB  - A significant number of youths use cigarettes, and more than half of the youths
      who smoke daily also use illicit drugs. The focus of these studies is on how
      exposure to nicotine affects subsequent responses to both nicotine and
      cannabinoids in adolescents compared with adults. We have shown previously that
      chronic treatment with nicotine produces sensitization to its locomotor
      activating effects in female and adult rats but not male adolescent rats. To
      better understand the effects of nicotine on adolescent and adult rats, rats were
      injected with nicotine or saline for 7 days and, on day 8, either challenged with
      delta-9-tetrahydrocannabinol (Delta 9-THC) or the cannabinoid agonist CP 55,940
      and tested for locomotor activity, or the brains were removed for quantitative
      autoradiography studies of the cannabinoid(1) receptor. A separate group of rats
      was treated with nicotine plus the cannabinoid antagonist AM 251 and then
      challenged with CP 55,940. In adolescent male rats, nicotine administration led
      to sensitization to the locomotor-decreasing effects of both Delta 9-THC and CP
      55,940, but in adult male rats, the response to either drug was unchanged
      compared to controls. The effect of nicotine on CP 55,940-mediated locomotor
      activity was blocked by co-administration of AM 251 with the nicotine. Further,
      cannabinoid receptor density was increased in the prelimbic prefrontal cortex,
      ventral tegmental area, and select regions of the hippocampus in adolescent male
      rats pretreated with nicotine compared to vehicle-treated controls. There were no
      significant changes in cannabinoid receptor binding, however, in any of the brain
      regions examined in adult males pretreated with nicotine. The prelimbic
      prefrontal cortex and the hippocampus have been shown previously to be involved
      in stimulant reinforcement; thus it is possible that these changes contribute to
      the unique behavioral effects of chronic nicotine and subsequent drug
      administration in adolescents compared with adults.

PMID- 19167481
TI  - Resveratrol metabolites in urine as a biomarker of wine intake in free-living
      subjects: The PREDIMED Study.
AB  - Several clinical and epidemiological studies have shown that moderate wine
      consumption may exert a protective effect against oxidative stress involved in
      several diseases, such as cardiovascular and neurodegenerative disorders.
      However, the epidemiological assessment of wine consumption has usually been
      obtained using self-reported questionnaires containing less reliable information
      for assessing total intake than nutritional biomarkers. A reliable biomarker for
      wine consumption is, therefore, needed. To validate urinary resveratrol
      metabolites (RMs) as a biomarker of wine consumption in a large cohort of free
      living subjects, 1000 consecutive subjects entering a substudy of the PREDIMED
      trial (Prevencion con Dieta Mediterranea) were evaluated. Data were collected in
      a validated semiquantitative food frequency questionnaire. RMs were measured in
      morning urine by LC-MS/MS. Urinary RM values correlated directly with reported
      daily amounts of wine consumed (r=0.895; p<0.001). One drink of wine per week can
      be detected. Using a cut-off of 411.4 nmol/g creatinine, the measurement of
      urinary RMs could discriminate wine consumers from non-wine consumers with a
      sensitivity of 93.3% (95% confidence interval (CI) 91.5-94.7%) and a specificity
      of 92.1% (CI 90.2-93.7%). Urinary RMs fulfill the criteria to be considered as a
      nutritional biomarker of wine consumption in a large sample of free-living
      subjects. This biomarker would provide an additional tool for investigating more
      precisely the relationship between wine consumption and health benefits.

PMID- 19167480
TI  - Interferon-alpha inhibits glucocorticoid receptor-mediated gene transcription via
      STAT5 activation in mouse HT22 cells.
AB  - Interferon (IFN)-alpha is an innate immune cytokine that induces significant
      depressive symptoms in clinical populations. A number of mechanisms have been
      considered regarding the relationship between IFN-alpha and depression, including
      the effects of IFN-alpha on the hypothalamic-pituitary-adrenal (HPA) axis. Here,
      we examined the impact of mouse interferon (mIFN)-alpha and its signaling
      pathways on the functioning of the glucocorticoid receptor (GR), which plays a
      key role in HPA axis regulation. mIFN-alpha treatment (100-1000 IU/ml) of HT22
      mouse hippocampal cells for 24h was found to significantly inhibit dexamethasone
      (DEX)-induced GR-mediated MMTV-luciferase activity and significantly decrease DEX
      induced GR-binding to its DNA response element. Of note, mIFN-alpha treatment for
      24h had no effect on DEX-induced GR translocation or GR protein expression.
      Inhibition of DEX-induced GR function by mIFN-alpha was significantly reversed by
      pharmacological inhibition of janus kinase/signal transducer and activator of
      transcription (Jak-STAT) signaling pathways, but not by inhibition of p38 mitogen
      activated protein kinase. Moreover, pretreatment of cells with siRNA targeted to
      STAT5, but not STAT1 or STAT2, significantly attenuated IFN-alpha inhibition of
      DEX-induced MMTV-luciferase activity. Immunoprecipitation experiments revealed
      nuclear co-immunoprecipitation of activated STAT5 and GR following IFN-alpha plus
      DEX treatment. Taken together, these results indicate that negative regulation of
      GR function by IFN-alpha in hippocampal HT22 cells is mediated by activation of
      Jak/STAT signaling pathways leading to nuclear STAT5-GR protein-protein
      interactions. Given the role of GR in depressive disorders, IFN-alpha effects on
      GR function in cells of hippocampal origin may contribute to HPA axis alterations
      and depressive symptoms in IFN-alpha-treated patients.

PMID- 19167482
TI  - Characterization of oxidized guanosine 5'-triphosphate as a viable inhibitor of
      soluble guanylyl cyclase.
AB  - The guanine base is prone to oxidation by free radicals regardless of the
      cellular moiety it is bound to. However, under conditions of oxidative stress, 8
      oxoguanosine triphosphate (oxo(8)GTP) formation has been shown to occur without
      oxidation of the guanine base in DNA. In vitro studies have suggested that
      oxo(8)GTP could impact G-protein signaling and RNA synthesis. Whether increased
      levels of oxo(8)GTP translate into cellular malfunction is unknown. Data
      presented herein show that oxo(8)GTP is formed in cell-free preparations as well
      as in PC12 cells after exposure to physiologically relevant oxidative conditions
      generated with 10 microM copper sulfate and 1 mM L-ascorbic acid (Cu/Asc). We
      also determined that oxo(8)GTP has biological activity as a potent inhibitor of
      nitric oxide-stimulated soluble guanylyl cyclase (sGC). The increase in oxo(8)GTP
      formation in purified GTP and PC12 cells exposed to Cu/Asc caused a significant
      reduction in the product of sGC activity, cGMP. This oxidation of GTP was
      attenuated by the addition of reduced glutathione under these same Cu/Asc
      conditions, thus preventing the decrease in sGC activity. This suggests that
      oxo(8)GTP is produced by free radicals in vivo and could have significant impact
      on cell functions regulated by sGC activity such as synaptic plasticity in the
      central nervous system.

PMID- 19167483
TI  - SIRT1 genetic variation and mortality in type 2 diabetes: interaction with
      smoking and dietary niacin.
AB  - SIRT1 protects cells against oxidative stress and aging. Its activity may be
      modulated by dietary niacin (vitamin B3) intake. We studied the association of
      SIRT1 genetic variation with mortality in subjects with increased oxidative
      stress (type 2 diabetes and smokers) in relation to dietary niacin. In 4573
      participants from the Rotterdam Study, including 413 subjects with prevalent and
      378 with incident type 2 diabetes, three SIRT1 tagging SNPs were genotyped and
      all-cause mortality was studied (average follow-up 12 years). We found no
      association between SIRT1 variation and mortality in the total population or in
      smokers. In subjects with prevalent type 2 diabetes, homozygous carriers of the
      most common SIRT1 haplotype, 1, had 1.5 times (95%CI 1.1-2.1) increased mortality
      risk compared to noncarriers. This risk further increased among smokers and those
      with low niacin intake. In the lowest tertile of niacin intake, mortality risk
      was increased 2.3 (95%CI 1.1-4.9) and 5.7 (95%CI 2.5-13.1) times for heterozygous
      and homozygous carriers of haplotype 1. Subjects with incident diabetes showed
      similar findings but only when they smoked. We conclude that in subjects with
      type 2 diabetes, SIRT1 genetic variation influences survival in interaction with
      dietary niacin and smoking. Correction of niacin deficiency and SIRT1 modulators
      may prolong the life span of patients with diabetes.

PMID- 19167484
TI  - Enhanced clonogenic survival induced by protein tyrosine phosphatase (PTP)
      inhibition after Cr(VI) exposure is mediated by c-Raf and Ras activity.
AB  - Our recent studies showed that maintenance of protein tyrosine phosphorylation by
      PTP inhibition enhanced cell growth, clonogenic survival, and mutagenesis after a
      single low-level Cr(VI) exposure, thereby suggesting that tyrosine
      phosphorylation-dependent signaling may govern inappropriate survival in human
      lung fibroblasts (HLFs). Our goal is to identify specific phospho-tyrosine
      regulator(s)/ downstream effectors involved in enhanced survival after Cr(VI)
      exposure and PTP inhibition. Phosphotyrosine profiling array showed that PTP
      inhibition following Cr(VI) exposure increased tyrosine phosphorylation of
      specific proteins, such as FGR and ABL, which are upstream regulators of both Erk
      and Akt pathways. To explore the roles of these pathways in the PTP-induced
      increase in clonogenic survival after Cr(VI) exposure, we examined the effect of
      combined Akt1 and Erk1/2 knockdown via siRNA technology. Akt1 and/or Erk1/2
      silencing had no effect on the PTP inhibitor-induced increase in survival
      following Cr(VI) exposure, suggesting the presence of non-Akt/non-Erk-mediated
      survival signaling. Interestingly, geldanamycin, an HSP90 inhibitor and non
      specific Raf inhibitor, abrogated the PTP inhibitor-mediated increase in survival
      following Cr(VI) exposure and abolished the expression/activity of c-Raf and
      activity of Mek. These findings prompted us to explore upstream regulators of
      Erk, i.e., Ras, c-Raf and Mek for their potential roles in clonogenic survival.
      GW5074, a specific c-Raf kinase inhibitor did not alter the effect of the PTP
      inhibitor but decreased Cr(VI)-mediated clonogenic lethality, potentially though
      Mek hyperactivation. A genetic approach with a c/a Mek1 mutant also showed that
      Mek activity was not directly associated with the PTP inhibitor effect. Finally,
      a genetic approach with d/n or c/a Ras and c-Raf mutants, showed that Ras and c
      Raf activities play a substantive role in enhancing clonogenic survival by PTP
      inhibition following Cr(VI) insult. In conclusion, these studies highlight a
      novel pro-survival mechanism for clonogenic survival in the face of genotoxic
      stress in the presence of PTP inhibition via an Erk/Mek-independent and Ras/c-Raf
      dependent regulation in normal human lung fibroblasts.

PMID- 19167485
TI  - The role of cell adhesion molecules in the progression of colorectal cancer and
      the development of liver metastasis.
AB  - Cell adhesion molecules (CAMs) play a significant role in the metastatic
      potential of colorectal cancer and thus mediate the prognosis of this common
      malignancy. The downregulation of cadherins and catenins facilitates tumour cell
      detachment from the primary site, while the expression of selectins, integrins
      and members of the immunoglobulin superfamily may support neoplastic progression,
      intravasation and malignant cell attachment to foreign tissue, leading to the
      development of metastases. The liver is the main host organ of colorectal
      metastatic lesions. The process of hepatic invasion originates in the sinusoids,
      where non-parenchymal cells interact with metastasising ones, through the
      expression of numerous CAMs, following complex molecular pathways. Concurrently,
      the selective expression of cell adhesion molecules on different organs and
      endothelia, in conjunction with the presence of dissimilar adhesion ligands on
      various colorectal cancer cell lines, suggest that CAMs may also mediate the
      selection of the host organ, for the development of distant colorectal
      metastases.

PMID- 19167486
TI  - B cell receptor-induced growth arrest and apoptosis in WEHI-231 immature B
      lymphoma cells involve cyclic AMP and Epac proteins.
AB  - Signaling by the B cell antigen receptor (BCR) is essential for B lymphocyte
      homeostasis and immune function. In immature B cells, ligation of the BCR
      promotes growth arrest and apoptosis, and BCR-driven balancing between pro
      apoptotic extracellular signal-regulated kinase 1 and 2 (ERK1/2) and anti
      apoptotic phosphoinositide 3-kinase-dependent Akt seems to define the final
      cellular apoptotic response. Dysfunction of these late BCR signaling events can
      lead to the development of immunological diseases. Here we report on novel cyclic
      AMP-dependent mechanisms of BCR-induced growth arrest and apoptosis in the
      immature B lymphoma cell line WEHI-231. BCR signaling to ERK1/2 and Akt requires
      cyclic AMP-regulated Epac, the latter acting as a guanine nucleotide exchange
      factor for Rap1 and H-Ras independent of protein kinase A. Importantly,
      activation of endogenously expressed Epac by a specific cyclic AMP analog
      enhanced the induction of growth arrest (reduced DNA synthesis) and apoptosis
      (nuclear condensation, annexin V binding, caspase-3 cleavage and poly-ADP-ribose
      polymerase processing) by the BCR. Our data indicate that cyclic AMP-dependent
      Epac signals to ERK1/2 and Akt upon activation of Rap1 and H-Ras, and is involved
      in BCR-induced growth arrest and apoptosis in WEHI-231 cells.

PMID- 19167488
TI  - Oral insulin delivery using nanoparticles based on microemulsions with different
      structure-types: optimisation and in vivo evaluation.
AB  - The purpose of this study was to optimise entrapment of insulin in
      poly(alkylcyanoacrylate) nanoparticles prepared from microemulsions with
      different microstructure containing isopropyl myristate, caprylocaproyl
      macrogolglycerides, polyglyceryl oleate and insulin solution and to investigate
      the in vitro release and bioactivity of insulin in nanoparticles dispersed in the
      microemulsion templates. Entrapment efficiency and release of insulin were
      studied using a reverse-phase HPLC assay. Morphology of the nanoparticles was
      examined with scanning electron microscopy. Bioactivity of insulin was studied
      using a streptozotocin-diabetic rat model. Nanoparticles were spherical with 200
      400 nm in size without significant difference between different microemulsion
      templates, types and amounts of monomer. Entrapment efficiency increased
      significantly with increasing monomer concentration but decreased with increasing
      aqueous fraction in the microemulsion template. Insulin loading however, showed
      an opposite trend. In vitro release profiles of insulin from the nanoparticles
      dispersed in the microemulsion templates were controlled by the monomer
      concentration only. In vivo, a consistent and significant hypoglycemic effect
      over controls was found for up to 36 h depending on the type of monomer. No
      significant serum insulin levels were detectable. This study showed that the
      strategy of delivering insulin orally, entrapped in nanoparticles and dispersed
      in a biocompatible microemulsion is promising and highlights the importance of
      optimisation studies in combination with in vivo experiments.

PMID- 19167487
TI  - Regulation of AMP-activated protein kinase by cAMP in adipocytes: roles for
      phosphodiesterases, protein kinase B, protein kinase A, Epac and lipolysis.
AB  - AMP-activated protein kinase (AMPK) is an important regulator of cellular energy
      status. In adipocytes, stimuli that increase intracellular cyclic AMP (cAMP) have
      also been shown to increase the activity of AMPK. The precise molecular
      mechanisms responsible for cAMP-induced AMPK activation are not clear.
      Phosphodiesterase 3B (PDE3B) is a critical regulator of cAMP signaling in
      adipocytes. Here we investigated the roles of PDE3B, PDE4, protein kinase B (PKB)
      and the exchange protein activated by cAMP 1 (Epac1), as well as lipolysis, in
      the regulation of AMPK in primary rat adipocytes. We demonstrate that the
      increase in phosphorylation of AMPK at T172 induced by the adrenergic agonist
      isoproterenol can be diminished by co-incubation with insulin. The diminishing
      effect of insulin on AMPK activation was reversed upon treatment with the PDE3B
      specific inhibitor OPC3911 but not with the PDE4 inhibitor Rolipram. Adenovirus
      mediated overexpression of PDE3B and constitutively active PKB both resulted in
      greatly reduced isoproterenol-induced phosphorylation of AMPK at T172. Co
      incubation of adipocytes with isoproterenol and the PKA inhibitor H89 resulted in
      a total ablation of lipolysis and a reduction in AMPK phosphorylation/activation.
      Stimulation of adipocytes with the Epac1 agonist 8-pCPT-2'O-Me-cAMP led to
      increased phosphorylation of AMPK at T172. The general lipase inhibitor Orlistat
      decreased isoproterenol-induced phosphorylation of AMPK at T172. This decrease
      corresponded to a reduction of lipolysis from adipocytes. Taken together, these
      data suggest that PDE3B and PDE4 regulate cAMP pools that affect the
      activation/phosphorylation state of AMPK and that the effects of cyclic AMP on
      AMPK involve Epac1, PKA and lipolysis.

PMID- 19167489
TI  - Use of global gene expression patterns in mechanistic studies of oestrogen action
      in MCF7 human breast cancer cells.
AB  - Over the years, the MCF7 human breast cancer cell line has provided a model
      system for the study of cellular and molecular mechanisms in oestrogen regulation
      of cell proliferation and in progression to oestrogen and antioestrogen
      independent growth. Global gene expression profiling has shown that oestrogen
      action in MCF7 cells involves the coordinated regulation of hundreds of genes
      across a wide range of functional groupings and that more genes are downregulated
      than upregulated. Adaptation to long-term oestrogen deprivation, which results in
      loss of oestrogen-responsive growth, involves alterations to gene patterns not
      only at early time points (0-4 weeks) but continuing through to later times (20
      55 weeks), and even involves alterations to patterns of oestrogen-regulated gene
      expression. Only 48% of the genes which were regulated > or =2-fold by oestradiol
      in oestrogen-responsive cells retained this responsiveness after long-term
      oestrogen deprivation but other genes developed de novo oestrogen regulation.
      Long-term exposure to fulvestrant, which resulted in loss of growth inhibition by
      the antioestrogen, resulted in some very large fold changes in gene expression up
      to 10,000-fold. Comparison of gene profiles produced by environmental chemicals
      with oestrogenic properties showed that each ligand gave its own unique
      expression profile which suggests that environmental oestrogens entering the
      human breast may give rise to a more complex web of interference in cell function
      than simply mimicking oestrogen action at inappropriate times.

PMID- 19167490
TI  - Epimerase activity of the human 11beta-hydroxysteroid dehydrogenase type 1 on 7
      hydroxylated C19-steroids.
AB  - Cytochrome P4507B1 7alpha-hydroxylates dehydroepiandrosterone (DHEA),
      epiandrosterone (EpiA) and 5alpha-androstane-3beta,17beta-diol (Adiol). 11beta
      Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) interconverts 7alpha- and 7beta
      forms. Whether the interconversion proceeds through oxido-reductive steps or
      epimerase activity was investigated. Experiments using [(3)H]-labelled 7beta
      hydroxy-DHEA, 7beta-hydroxy-EpiA and 7beta-hydroxy-Adiol showed the (3)H-label to
      accumulate in the 7-oxo-DHEA trap but not in 7-oxo-EpiA or 7-oxo-Adiol traps.
      Computed models of 7-oxygenated steroids docked in the active site of 11beta-HSD1
      either in a flipped or turned form relative to cortisone and cortisol. 7-Oxo
      steroid reduction in 7alpha- or 7beta-hydroxylated derivatives resulted from
      either turned or flipped forms. 11beta-HSD1 incubation in H(2)(18)O medium with
      each 7-hydroxysteroid did not incorporate (18)O in 7-hydroxylated derivatives of
      EpiA and Adiol independently of the cofactor used. Thus oxido-reductive steps
      apply for the interconversion of 7alpha- and 7beta-hydroxy-DHEA through 7-oxo
      DHEA. Epimerization may proceed on the 7-hydroxylated derivatives of EpiA and
      Adiol through a mechanism involving the cofactor and Ser(170). The
      physiopathological importance of this epimerization process is related to 7beta
      hydroxy-EpiA production and its effects in triggering the resolution of
      inflammation.

PMID- 19167491
TI  - Lessons from the gonadotropin-regulated long chain acyl-CoA synthetase (GR-LACS)
      null mouse model: a role in steroidogenesis, but not result in X-ALD phenotype.
AB  - Gonadotropin-regulated long chain fatty acid Acyl-CoA synthetase (GR-LACS), is a
      member of the LACS family that is regulated by gonadotropin in the rat Leydig
      cell (LC). Its mouse/human homologs, lipidosin/bubblegum, have been suggested to
      participate in X-linked adrenoleukodystrophy (X-ALD), an adreno/neurodegenerative
      disorder with accumulation of very long chain fatty acids (VLCFA) in tissues and
      plasma. To further gain insights into its regulatory function, a GR
      LACS/lipidosin null mouse was generated. No apparent phenotypic abnormalities
      were observed in the X-ALD target tissues (brain, testis, adrenal). Nuclear
      inclusions seen in mice >15 month-old, were present in LC of 9 month-old GR-LACS(
      /-) mice. LC of the null mice showed refractoriness to the gonadotropin-induced
      desensitization of testosterone production that is observed in adult animals.
      LCFAs were moderately increased in the testis, ovary and brain, but not in the
      adrenal gland of GR-LACS(-/-) mice, with no major changes in VLCFA. No change in
      LACS activity was observed in these tissues, suggesting a compensatory mechanism
      exhibited by other LACS members. The GR-LACS(-/-) model did not support its
      association with X-ALD. These studies revealed a role of GR-LACS in reducing the
      aging process of the LC, and its participation in gonadotropin-induced testicular
      desensitization of testosterone production.

PMID- 19167492
TI  - Potential of l-buthionine sulfoximine to enhance the apoptotic action of
      estradiol to reverse acquired antihormonal resistance in metastatic breast
      cancer.
AB  - L-Buthionine sulfoximine (BSO) is a potent inhibitor of glutathione biosynthesis
      and studies have shown that it is capable of enhancing the apoptotic effects of
      several chemotherapeutic agents. Previous studies have shown that long-term
      antihormonal therapy leads to acquired drug resistance and that estrogen, which
      is normally a survival signal, is a potent apoptotic agent in these resistant
      cells. Interestingly, we have developed an antihormone-resistant breast cancer
      cell line, MCF-7:2A, which is resistant to estrogen-induced apoptosis but has
      elevated levels of glutathione. In the present study, we examined whether BSO is
      capable of sensitizing antihormone-resistant MCF-7:2A cells to estrogen-induced
      apoptosis. Our results showed that treatment of MCF-7:2A cells with 1nM E2 plus
      100muM BSO combination for 1 week reduced the growth of these cells by almost 80
      90% whereas the individual treatments had no significant effect on growth. TUNEL
      and 4',6-diamidino-2-phenylindole (DAPI) staining showed that the inhibitory
      effect of the combination treatment was due to apoptosis. Our data indicates that
      glutathione participates in retarding apoptosis in antihormone-resistant human
      breast cancer cells and that depletion of this molecule by BSO may be critical in
      predisposing resistant cells to estrogen-induced apoptosis.

PMID- 19167493
TI  - Role of estrogen receptor alpha in membrane-initiated signaling in neural cells:
      interaction with IGF-1 receptor.
AB  - The mechanisms of action of estradiol in the nervous system involve nuclear
      initiated steroid signaling and membrane-initiated steroid signaling. Estrogen
      receptors (ERs) are involved in both mechanisms. ERalpha interacts with the
      signaling of IGF-1 receptor in neural cells: ERalpha transcriptional activity is
      regulated by IGF-1 receptor signaling and estradiol regulates IGF-1 receptor
      signaling. The interaction between ERalpha and the IGF-1 receptor in the brain
      may occur at the plasma membrane of neurons and glial cells. Caveolin-1 may
      provide the scaffolding for the interaction of different membrane-associated
      molecules, including voltage-dependent anion channel, ERalpha and IGF-I receptor.

PMID- 19167494
TI  - New lead compounds in the search for pure antiglucocorticoids and the
      dissociation of antiglucocorticoid effects.
AB  - Antiglucocorticoids that act as antagonists at the glucocorticoid receptor (GR)
      level may be used to block or modulate the undesirable effects of glucocorticoid
      excess (from endogenous or exogenous origin). RU486 developed in the early 80s,
      is an antiglucocorticoid but also a potent antiprogestin and abortifacient,
      nevertheless it still remains as the only GR antagonist drug in the market.
      Further on, in view of the variety of physiological processes in which
      glucocorticoids are involved, selective antiglucocorticoids that can block only
      some of these processes (eventually with tissue specificity) would be highly
      desirable. The bridged pregnane 21-hydroxy-6,19-epoxyprogesterone, was developed
      as an alternative lead being an antagonist of the GR with no affinity for
      mineralocorticoid and progesterone receptors. Antagonistic activity was evidenced
      by partial blocking of dexamethasone induction of tyrosine aminotransferase (TAT)
      and thymocyte apoptosis. Replacement of the oxygen bridge by a sulfur bridge gave
      a less bent, more flexible molecule. 21-Hydroxy-6,19-epithioprogesterone
      exhibited improved antiapoptotic activity on thymocytes but was not effective
      blocking TAT induction. This selectivity was improved further by oxidation to the
      sulfone. The sulfone but not the reduced compound also reverted the dexamethasone
      mediated inhibition of NFkappaB activity in HeLa cells. Blocking of the apoptotic
      effect of TNFalpha by dexamethasone in the L929 cell line (mouse fibroblasts),
      was only reverted partially by the sulfone which exhibited a mild
      agonistic/antagonistic activity in this assay. None of these compounds showed
      antiprogestin activity. Similar overall molecular shapes but more lipophylic and
      with higher metabolic stability were obtained by introduction of a methylene
      bridge (6,19-methanoprogesterone) or by a direct bond between C-6 and C-19 (6,19
      cycloprogesterone and its 21-hydroxy derivative). The latter highly bent steroids
      showed affinity for the GR. Recently we performed molecular dynamics simulations
      of GR-ligand complexes to investigate the molecular basis of the passive
      antagonism exhibited by 21-hydroxy-6,19-epoxyprogesterone. On the basis of our
      findings, we proposed that the passive antagonist mode of action of this
      antiglucocorticoid analog resides, at least in part, in the incapacity of GR-21
      hydroxy-6,19-epoxyprogesterone complex to dimerize, making the complex unable to
      activate gene transcription.

PMID- 19167495
TI  - Clinical applications for estetrol.
AB  - In this paper the potential clinical applications for the human fetal estrogen
      estetrol (E(4)) are presented based on recently obtained data in preclinical and
      clinical studies. In the past E(4) has been classified as a weak estrogen due to
      its rather low estrogen receptor affinity. However, recent research has
      demonstrated that due to its favorable pharmacokinetic properties, especially the
      slow elimination and long half-life, E(4) is an effective orally bioavailable
      estrogen agonist with estrogen antagonistic effects on the breast in the presence
      of estradiol. Based on the pharmacokinetic properties, the pharmacological
      profile and the safety and efficacy results in human studies, E(4) seems
      potentially suitable as a drug for human use in applications such as hormone
      replacement therapy (vaginal atrophy and vasomotor symptoms), contraception,
      osteoporosis and breast cancer.

PMID- 19167496
TI  - 17Beta-hydroxysteroid dehydrogenase enzymes and breast cancer.
AB  - Sex steroids play an important role in the development and differentiation in
      several tissues. Biologically active hormones that are locally converted in
      endocrine organs in the tissue where they exert their effects without release
      into extracellular space is a field of endocrinology that has been called
      intracrinology. In pre-menopausal women the ovary is the main source of
      estrogens, but in post-menopausal women the estrogen production as main site of
      synthesis moves to peripheral tissues and almost all of the sex steroids are
      synthesised from precursors of adrenal origin. In breast cancer 60-80% of the
      tumors express high levels of oestrogen receptor (ER) alpha which gives estrogen
      a proliferative effect. Breast tumors tend to have a higher intratumoral estrogen
      concentration than normal breast tissue and plasma, and in situ synthesis and the
      metabolism of estrogens is believed to be of great importance for the development
      and progression of the disease. The activity of estrogen metabolizing enzymes in
      breast are mainly aromatase, estrone sulfatases and 17HSD enzymes. 17HSD1 and
      17HSD2 are the family members known to be of main importance in breast cancer.
      High expression of 17HSD1 has been associated to poor prognosis in breast cancer
      and late relapse among patients with ER-positive tumors. One of the mechanisms
      behind high 17HSD1 expression is gene amplification. Low or absent expression of
      17HSD2 is associated to decreased survival in ER-positive breast cancer. 17HSD14
      is one of the latest discovered 17HSD enzymes, transfection of 17HSD14 in human
      breast cancer cells significantly decreased the levels of estradiol in the
      culture medium. Low expression of 17HSD14 mRNA expression in breast cancer was
      correlated to decreased survival. The understanding of intratumoral synthesis of
      sex steroids in breast cancer is crucial to understand the disease both in pre-
      and post-menopausal women. Further studies are desirable to state the direct role
      of these enzymes in breast cancer and which patients that may benefit from new
      therapeutic strategies targeting 17HSD enzymes. The new inhibitors targeting
      17HSD1 have shown promising results in pre-clinical studies to have clinical
      potential in the future.

PMID- 19167497
TI  - Estrogenic activities of extracts of Chinese licorice (Glycyrrhiza uralensis)
      root in MCF-7 breast cancer cells.
AB  - Despite the wide use of Chinese licorice root (Glycyrrhiza uralensis) for the
      treatment of menopausal complaints, little is known on its potential estrogenic
      properties, and available information relative to its effects on cell
      proliferation is contradictory. In this study, the estrogenic properties of
      licorice root were evaluated in vitro by use of several assays. The effects of
      increasing concentrations of a DMSO extract of licorice root on the growth of MCF
      7 breast cancer cells were biphasic. The extract showed an ER-dependent growth
      promoting effect at low concentrations and an ER-independent anti-proliferative
      activity at high concentrations. In further experiments, licorice root was
      sequentially extracted to yield four fractions: hexane, EtOAc, methanol and
      H(2)O. Only the EtOAc extract had effects on cell proliferation similar to the
      DMSO extract. The hexane extract had no effect on cell growth. In contrast, the
      methanol and water extracts showed an ER-independent, growth-promoting effect.
      Similar to its effects on cell proliferation, the EtOAc extract had a biphasic
      effect on S phase cell cycle distribution and the level of PCNA protein. This
      extract-induced transactivation of endogenous ERalpha in MCF-7 cells, supported
      by inducing down-regulation of ERalpha protein and mRNA levels, and up-regulation
      of ERalpha target genes pS2 and GREB1. These results suggest that the activity of
      licorice root and the balance between increased risk for cancer and prevention of
      estrogen-dependent breast cancer may depend on the amount of dietary intake.

PMID- 19167498
TI  - Evidence for both neuronal cell autonomous and nonautonomous effects of methyl
      CpG-binding protein 2 in the cerebral cortex of female mice with Mecp2 mutation.
AB  - Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by
      mutations in the gene MECP2, encoding methyl-CpG-binding protein 2 (MeCP2). Few
      studies have explored dendritic morphology phenotypes in mouse models of RTT and
      none have determined whether these phenotypes in affected females are cell
      autonomous or nonautonomous. Using confocal microscopy analysis we have examined
      the structure of dendrites and spines in the motor cortex of wild-type (WT) and
      Mecp2-mutant mice expressing green fluorescent protein (GFP). In Mecp2 GFP female
      mice age 6-7 months we found significant decreases in the density of spines,
      width of dendrites, size of spine heads, while increases were found in the length
      of spine necks, dendritic irregularities, spineless spots, and long spines. We
      show for the first time that a lower density of spines and smaller spine head
      area are phenotypes that distinguish MeCP2+ from MeCP2- dendrites in female Mecp2
      GFP mice. In Mecp2 GFP male mice at three weeks of age, we found reduced spine
      density, thinner apical oblique dendrites and increased dendritic irregularities
      and long spines. Significantly, the changes affected both MeCP2- and MeCP2+
      neurons, pointing to the ability of MeCP2- to impact the structure of MeCP2+
      neurons. Our findings are evidence that MeCP2 deficiency results in both cell
      autonomous and nonautonomous changes.

PMID- 19167499
TI  - Abeta-specific Th2 cells provide cognitive and pathological benefits to
      Alzheimer's mice without infiltrating the CNS.
AB  - We have found that a small number of purified Th2-biased Abeta-specific T cells
      are sufficient to provide profound cognitive and pathological benefits in an
      APP+PS1 mouse model for Alzheimer's disease. Six weeks after receiving T cell
      infusions, cognitively-impaired mice performed significantly better in working
      memory tasks, which correlated with higher plasma levels of soluble Abeta.
      Pathological analysis of the hippocampus revealed a 30% decrease of plaque
      associated microglia and less vascular amyloidosis in T cell treated mice. The
      infusion of Abeta-specific Th2 cells also reduced plasma levels of IFN-gamma, TNF
      alpha, GM-CSF, IL-2 and IL-4, which are elevated in untreated APP+PS1 mice. No
      significant immune cell infiltration and no anti-Abeta antibody titers occurred
      in the T cell treated mice. These results demonstrate that Abeta-specific Th2
      cells are sufficient to reverse cognitive impairment and provide multiple
      pathological benefits in an Alzheimer's mouse model.

PMID- 19167500
TI  - TAT-Bcl-x(L) improves survival of neuronal precursor cells in the lesioned
      striatum after focal cerebral ischemia.
AB  - Cerebral ischemia activates endogenous neurogenesis in the subventricular zone
      (SVZ) and the dentate gyrus. Consecutively, SVZ-derived neural precursors migrate
      towards ischemic lesions. However, functional relevance of activated neurogenesis
      is limited by poor survival of new-born precursors. We therefore employed the HI
      virus-derived fusion protein TAT-Bcl-x(L) to study the effects of acute anti
      apoptotic treatment on endogenous neurogenesis and functional outcome after
      transient cerebral ischemia in mice. TAT-Bcl-x(L) treatment led to significantly
      reduced acute ischemic cell death (128+/-23 vs. 305+/-65 TUNEL+ cells/mm(2) in
      controls) and infarct volumes resulting in less motor deficits and improved
      spatial learning. It significantly increased survival of doublecortin (Dcx)
      positive neuronal precursors (389+/-96 vs. 213+/-97 Dcx+ cells in controls) but
      did not enhance overall post-ischemic cell proliferation or lesion-specific
      neuronal differentiation 28 days after ischemia. Our data demonstrate that post
      stroke TAT-Bcl-x(L)-treatment results in acute neuroprotection, improved
      functional outcome, and enhanced survival of lesion-specific neuronal precursor
      cells after cerebral ischemia in mice.

PMID- 19167501
TI  - Molecular interaction between parkin and PINK1 in mammalian neuronal cells.
AB  - Parkinson's disease (PD) is characterized by the deterioration of dopaminergic
      neurons in the pars compacta of substantia nigra and the formation of
      intraneuronal protein inclusions. The etiology of PD is not known, but the recent
      identification of several mutation genes in familial PD has provided a rich
      understanding of the molecular mechanisms of PD pathology. Mutations in PTEN
      induced putative kinase 1 (PINK1) and parkin are linked to early-onset autosomal
      recessive forms of familial PD. Here we show molecular and functional
      interactions between parkin and PINK1. Parkin selectively binds to PINK1 and
      upregulates PINK1 levels. In addition, PINK1 reduces the solubility of parkin,
      which induces the formation of microtubule-dependent cytoplasmic aggresomes. Our
      findings reveal that parkin and PINK1 affect each other's stability, solubility
      and tendency to form aggresomes, and have important implications regarding the
      formation of Lewy bodies.

PMID- 19167502
TI  - Production of the p24 capsid protein from HIV-1 subtype C in Arabidopsis thaliana
      and Daucus carota using an endoplasmic reticulum-directing SEKDEL sequence in
      protein expression constructs.
AB  - An optimized gene expression construct was designed in order to increase the
      accumulation of the HIV-1 subtype C p24 protein in Arabidopsis thaliana and
      carrot (Daucus carota) plants. An ER retention signal was introduced into the
      genetic construct generating a p24 protein containing a SEKDEL amino acid
      sequence at its C-terminus. Mature A. thaliana plants and carrot cells were
      transformed using Agrobacterium tumefaciens carrying the improved
      pGreen0229/p24_SEKDEL vector. Several transgenic plant lines were obtained from
      both plant species by growth on selective medium and confirmed by PCR.
      Transformed lines were analyzed for p24 protein content by western blotting using
      anti-p24-specific antibodies and by Southern blotting to establish the number of
      copies of the insert in the plant nuclear genome. To estimate the accumulation
      levels of p24 protein in the plants, ELISA was run using soluble plant extracts.
      By comparing these results with our previous findings, the ER retention signal
      increased the level of p24 protein fivefold in the A. thaliana plants. In carrot
      taproot, the content of p24_SEKDEL protein was approximately half of that in
      Arabidopsis on a fresh weight basis and was stable in planta for several months.
      However, on a total soluble protein basis, carrots produced considerable higher
      levels of the p24_SEKDEL protein than Arabidopsis.

PMID- 19167503
TI  - Morphometric abnormalities and hyperanxiety in genetically epileptic rats: a
      model of psychiatric comorbidity?
AB  - BACKGROUND: Imaging studies of epilepsy patients with comorbid affective
      disturbance demonstrate morphometric changes in limbic brain regions implicated
      in psychiatric disease. Genetic Absence Epilepsy Rats from Strasbourg (GAERS),
      specifically bred for their epilepsy phenotype, also exhibit elevated anxiety
      like behaviors suggesting a common causality. Here we examined whether relevant
      cerebral morphological alterations exist in this rat strain using volumetric
      measurements and large deformation high dimensional mapping (HDM-LD), a tool
      recently validated to produce accurate three-dimensional surface representations
      of the hippocampus. METHODS: Volumetric MRI and the Open Field test of anxiety
      were performed in adult female GAERS (n=12) and Non-Epileptic Controls (NEC;
      n=11). The volumes of selected brain regions, including cortex, hippocampus,
      amygdala, thalamus, hypothalamus and lateral ventricles, were measured using
      Region-Of-Interest analysis from the MRI data and total volumes compared between
      the two strains. RESULTS: GAERS had increased amygdala (right: p=0.003; left
      p<0.001), cortices (right: p=0.006; left p=0.012) and ventricular volumes
      (p=0.002) when compared with NEC rats. Further, HDM-LD showed GAERS to have
      hippocampal volume loss in two regions: the medial hippocampal surface
      immediately caudal to the hippocampal commissure, and the lateral hippocampal
      surface over the mid-portion of the septotemporal axis. GAERS exhibited increased
      anxiety in the Open Field compared with NEC rats: reduced distance traveled
      (p<0.001) and reduced time in the centre area (p=0.042). CONCLUSIONS:
      Morphometric brain changes in GAERS could be relevant to their hyperanxious and
      epileptic phenotypes. This model may be useful in illuminating the pathogenesis
      of affective disorders generally, as well as modeling psychiatric comorbidities
      of epilepsy.

PMID- 19167504
TI  - Automatic cropping of MRI rat brain volumes using pulse coupled neural networks.
AB  - The Pulse Coupled Neural Network (PCNN) was developed by Eckhorn to model the
      observed synchronization of neural assemblies in the visual cortex of small
      mammals such as a cat. In this paper we show the use of the PCNN as an image
      segmentation strategy to crop MR images of rat brain volumes. We then show the
      use of the associated PCNN image 'signature' to automate the brain cropping
      process with a trained artificial neural network. We tested this novel algorithm
      on three T2 weighted acquisition configurations comprising a total of 42 rat
      brain volumes. The datasets included 40 ms, 48 ms and 53 ms effective TEs,
      acquisition field strengths of 4.7 T and 9.4 T, image resolutions from 64x64 to
      256x256, slice locations ranging from +6 mm to -11 mm AP, two different surface
      coil manufacturers and imaging protocols. The results were compared against
      manually segmented gold standards and Brain Extraction Tool (BET) V2.1 results.
      The Jaccard similarity index was used for numerical evaluation of the proposed
      algorithm. Our novel PCNN cropping system averaged 0.93 compared to BET scores
      circa 0.84.

PMID- 19167505
TI  - Neural correlates of semantic ambiguity processing during context verification.
AB  - Understanding the relevant meaning of a word with different meanings (homonym) in
      a given context requires activation of the neural representations of the relevant
      meaning and inhibition of the irrelevant meaning. The cognitive demand of such
      disambiguation is highest when the dominant, yet contextually irrelevant meaning
      of a polar homonym must be suppressed. This central process (semantic inhibition)
      for lexico-semantic ambiguity resolution was monitored with fMRI during semantic
      context verifications. Twenty-two healthy volunteers decided whether congruent or
      incongruent target words fitted into the contexts established by preceding
      sentences. Half of the sentences ended with a homonym, thereby allowing to cross
      the factors ambiguity and semantic congruency. BOLD increases related to the
      inhibitory attentional control over non-selected meanings during ambiguity
      processing occurred in a brain network including left dorsolateral prefrontal
      cortex (DLPFC), bilateral angular gyrus (AG), bilateral anterior superior
      temporal gyrus (aSTG) as well as right ventromedial temporal lobe. In left DLPFC
      (BA 46/9) and left AG (BA 39) BOLD activity to target words of the incongruent
      ambiguous condition correlated with the individual amount of semantic
      interference experienced by the subjects. BOLD increases of incongruent versus
      congruent semantic verifications occurred in bilateral inferior frontal gyrus.
      The results of the present study suggest a specific role of left DLPFC and AG in
      the resolution of semantic interference from contextually inappropriate homonym
      meanings. These fronto-parietal areas might exert inhibitory control over
      temporal regions in service of attentional selection between relevant and
      irrelevant homonym meanings, by creating a sufficient activation difference
      between their respective representations.

PMID- 19167506
TI  - Commonalities in the neural mechanisms underlying automatic attentional shifts by
      gaze, gestures, and symbols.
AB  - Eye gaze, hand-pointing gestures, and arrows automatically trigger attentional
      shifts. Although it has been suggested that common neural mechanisms underlie
      these three types of attentional shifts, this issue remains unsettled. We
      measured brain activity using fMRI while participants observed directional and
      non-directional stimuli, including eyes, hands, and arrows, to investigate this
      issue. Conjunction analyses revealed that the posterior superior temporal sulcus
      (STS), the inferior parietal lobule, the inferior frontal gyrus, and the
      occipital cortices in the right hemisphere were more active in common in response
      to directional versus non-directional stimuli. These results suggest
      commonalities in the neurocognitive mechanisms underlying the automatic
      attentional shifts triggered by gaze, gestures, and symbols.

PMID- 19167507
TI  - Sustained and transient language control in the bilingual brain.
AB  - Bilingual speakers must have effective neural mechanisms to control and manage
      their two languages, but it is unknown whether bilingual language control
      includes different control components. Using mixed blocked and event-related
      designs, the present study explored the sustained and transient neural control of
      two languages during language processing. 15 Chinese-English bilingual speakers
      were scanned when they performed language switching tasks. The results showed
      that, compared to the single language condition, sustained bilingual control
      (mixed language condition) induced activation in the bilateral inferior frontal,
      middle prefrontal and frontal gyri (BA 45/46). In contrast, relative to the no
      switch condition, transient bilingual control (language switching condition)
      activated the left inferior parietal lobule (BA 2/40), superior parietal lobule
      (BA 7), and middle frontal gyrus (BA 11/46). Importantly, the right superior
      parietal activity correlated with the magnitude of the mixing cost, and the left
      inferior and superior parietal activity covaried with the magnitude of the
      asymmetric switching costs. These results suggest that sustained and transient
      language control induced differential lateral activation patterns, and that
      sustained and transient activities in the human brain modulate the behavioral
      costs during switching-related language control.

PMID- 19167508
TI  - A putative high risk diplotype of the G72 gene is in healthy individuals
      associated with better performance in working memory functions and altered brain
      activity in the medial temporal lobe.
AB  - G72 is a vulnerability gene for schizophrenia and affective psychosis, disorders
      that are characterized by deficits in working memory. In the present study we
      investigated whether the G72 genotype influences verbal and spatial working
      memory functions in healthy individuals. Working memory was assessed at the
      behavioural level in 423 subjects using the spatial span of the Wechsler Memory
      Scale (spatial working memory) and the letter-number-span test (verbal working
      memory). In a sub-sample of 83 subjects, we assessed working memory functions
      also at the neural level using functional magnetic resonance imaging during a
      classical letter variant of the n-back task. Unexpectedly the high risk allele
      carriers performed better in the verbal working memory task than the other
      subjects. These behavioural differences were accompanied by brain activation
      differences in the right parahippocampus, a brain region that plays a major role
      in schizophrenia and affective disorders. The high risk variant of a
      vulnerability gene therefore does not necessarily have to negatively affect
      cognitive abilities per se, but may even have beneficial effects on cognitive
      functions in the non-affected population.

PMID- 19167510
TI  - Individual, temporal, and population-level variations in circulating 11
      ketotestosterone and 17beta-estradiol concentrations in the oyster toadfish
      Opsanus tau.
AB  - Sex steroid hormones are important for reproduction in all vertebrates, but few
      studies examine inter-individual, temporal, and population-level variations, as
      well as environmental influences on circulating steroid levels within the same
      species. In this study we analyzed plasma 11-ketotoestosterone (11-KT) and 17beta
      estradiol (E(2)) levels in the oyster toadfish to test for 1) individual and
      temporal variations by serially sampling the same individuals during the
      reproductive and post-reproductive period, 2) variations in steroid levels among
      toadfish obtained from different sources or maintained under different holding
      conditions, and 3) correlations with environmental parameters. Results from
      serial sampling showed marked inter-individual variations in male 11-KT levels in
      two separate groups of toadfish, but no temporal differences from June to
      September. Females also showed inter-individual variations in E(2)
      concentrations, but most had elevated levels late in the reproductive season
      coincident with oocyte growth prior to winter quiescence. E(2) concentration, but
      not 11-KT, was positively correlated with water temperature, and negatively
      correlated with daylength and lunar phase. Maricultured toadfish held under
      constant conditions had elevated levels of E(2) and 11-KT that should be
      considered when using these fish for experimentation. This study provides
      important comparative information on the relationship between individual
      variations in steroid levels, and how they relate to physiological and
      environmental correlates in a model marine teleost.

PMID- 19167511
TI  - Growth and protein synthesis of barramundi, Lates calcarifer, fed lupin as a
      partial protein replacement.
AB  - Protein synthesis is an essential growth process in all animals. Little
      information is available on post-prandial protein synthesis and even less where
      different protein sources are compared. Protein synthesis was measured at 4 and
      24 h after feeding juvenile barramundi in order to determine the effect of using
      lupin as a partial protein replacement for fish meal on the post-prandial protein
      metabolism. Juvenile barramundi (4.3+/-0.6 g) were held in a recirculation system
      (27 degrees C, salinity 10 per thousand and 24 h light) for 15 days. Fish were
      fed one of two isonitrogenous isoenergetic diets (40% crude protein, 16% lipid
      and 18.5 GE MJ kg(-1)). One diet was formulated with 100% fish meal as the
      protein source while the other had 45% of the protein replaced with lupin
      ingredients (lupin kernel meal (Lupinus angustifolius) and lupin protein
      concentrate). All fish were fed a ration of 6%.d(-1) and feed intake was not
      significantly different between the two diets. Specific growth rate (SGR) and
      growth efficiency (in relation to protein (PPV) and energy (PEV)) were 6.5+/
      0.14%.d(-1), 43.8+/-2.72% and 38.31+/-1.56%, respectively, and were not
      significantly different between the two diets. There was no significant
      difference in protein synthesis between the two diets at 4 and 24 h after
      feeding, however protein synthesis was significantly higher 4 h after feeding
      than at 24 h (p=0.02). Neither growth performance nor protein metabolism was
      altered by replacing 45% of the protein with lupin protein and indicated this to
      be a suitable protein source for barramundi feeds.

PMID- 19167509
TI  - The effect of template choice on morphometric analysis of pediatric brain data.
AB  - The present study investigated the "template effect" on the morphometric analysis
      of a pediatric brain MRI database obtained from 8-year-old children through
      various measures of surface and volumetric morphologies. We first constructed an
      age-appropriate template from an independent set of pediatric brain images and
      then compared it with a well-known adult brain template, the ICBM152, in terms of
      the morphometric features that resulted from our pediatric database. The
      individual cortical surface acquired based on the pediatric template exhibited,
      on average, a significantly thinner cortex (-1.66+/-1.60%, t=-15.18), larger
      cortical surface areas (0.31+/-0.70%, t=6.52), and a higher degree of cortical
      folding (0.08+/-0.13%, t=8.72) while compared with those based on the adult
      template. We also found a significant increase in the cerebrospinal fluid volume
      (-2.63+/-4.84) for the adult template based brains and the cortical gray matter
      (GM) volume (6.10+/-7.81) for the pediatric template based brains. The cross
      correlation of pediatric template based individual brain data (0.95 without brain
      mask) was significantly higher than those of adult template based (0.88) and the
      amount of deformation during non-linear spatial normalization was significantly
      reduced when using the pediatric template (average magnitude of deformation in
      the cortical GM class: 1.71 mm vs. 2.23 mm, t=12.39). In addition, an "internal"
      pediatric template, taken from the study subjects themselves, was generated and
      compared with the "external" pediatric template for reference. There was no
      significant difference between these two pediatric brain templates and associated
      tissue probability maps. The results show that it is necessary to be cautious
      when interpreting results from pediatric imaging studies based on adult reference
      data.

PMID- 19167512
TI  - Genotoxicity of agricultural soils in the vicinity of industrial area.
AB  - Soil samples from agricultural fields (cultivated) in the vicinity of industrial
      area of Ghaziabad City (India) were collected. In this city, wastewater coming
      from both industrial and domestic sources and without any treatment is used to
      irrigate the food crops. This practice has been polluting the soil and pollutants
      might reach the food chain. Gas chromatographic analysis show the presence of
      certain organochlorine (DDE, DDT, dieldrin, aldrin and endosulfan) and
      organophosphorus (dimethoate, malathion, methylparathion and chlorpyrifos)
      pesticides in soil samples. Samples were extracted using different solvents, i.e.
      methanol, chloroform, acetonitrile, hexane and acetone (all were HPLC-grade, SRL,
      India), and the extracts were assayed for genotoxic potential using Ames
      Salmonella/microsome test, DNA repair defective mutants and bacteriophage lambda
      systems. TA98 and TA100 were found to be the most sensitive strains to all the
      soil extracts tested. Methanol extracts exhibited a maximum mutagenicity with
      TA98 strain {540 (-S9) and 638 (+S9) revertants/g of soil} and 938 (-S9) and 1008
      (+S9) revertants/g of soil with TA100 strain. The damage in the DNA repair
      defective mutants was found maximum with methanolic extract followed by
      acetonitrile, chloroform, hexane and acetone at the dose level of 40 microl/ml
      culture after 6h of treatment. The survival was 25, 30, 32, 33 and 35% in polA
      strain after 6h of treatment when tested with wastewater irrigated soil extracts
      of methanol, acetonitrile, chloroform, hexane and acetone, respectively. A
      significant decrease in the plaque forming units of bacteriophage lambda was also
      observed when treated with 40 microl of test samples. Present results showed that
      methanolic extracts of soil were more toxic than other soil extracts. The soil is
      accumulating a large number of pollutants due to wastewater irrigation and this
      practice of accumulation has an impact on soil health.

PMID- 19167513
TI  - Intralaboratory and interlaboratory evaluation of the EpiDerm 3D human
      reconstructed skin micronucleus (RSMN) assay.
AB  - A novel in vitro human reconstructed skin micronucleus (RSMN) assay has been
      developed using the EpiDerm 3D human skin model [R. D. Curren, G. C. Mun, D. P.
      Gibson, and M. J. Aardema, Development of a method for assessing micronucleus
      induction in a 3D human skin model EpiDerm, Mutat. Res. 607 (2006) 192-204]. The
      RSMN assay has potential use in genotoxicity assessments as a replacement for in
      vivo genotoxicity assays that will be banned starting in 2009 according to the EU
      7th Amendment to the Cosmetics Directive. Utilizing EpiDerm tissues reconstructed
      with cells from four different donors, intralaboratory and interlaboratory
      reproducibility of the RSMN assay were examined. Seven chemicals were evaluated
      in three laboratories using a standard protocol. Each chemical was evaluated in
      at least two laboratories and in EpiDerm tissues from at least two different
      donors. Three model genotoxins, mitomycin C (MMC), vinblastine sulfate (VB) and
      methyl methanesulfonate (MMS) induced significant, dose-related increases in
      cytotoxicity and MN induction in EpiDerm tissues. Conversely, four dermal non
      carcinogens, 4-nitrophenol (4-NP), trichloroethylene (TCE), 2-ethyl-1,3
      hexanediol (EHD), and 1,2-epoxydodecane (EDD) were negative in the RSMN assay.
      Results between tissues reconstructed from different donors were comparable.
      These results indicate the RSMN assay using the EpiDerm 3D human skin model is a
      promising new in vitro genotoxicity assay that allows evaluation of chromosome
      damage following "in vivo-like" dermal exposures.

PMID- 19167514
TI  - Using the Salmonella assay to delineate the dispersion routes of mutagenic
      compounds from coal wastes in contaminated soil.
AB  - The mutagenicity of acidic and organic extracts of surface soil under the
      influence of a coal-fired power plant was evaluated by Salmonella/microsome assay
      using strains TA97a, TA98 and TA100 in the absence and presence of exogenous
      metabolic systems (S9 mix). Additionally, strains YG1041 and YG1042 (sensitive to
      nitroderivatives) were used for the organic extracts. In general, the responses
      were higher in the organic extracts in the presence of S9 mix. The comparison
      between strains TA98 and TA100 and their derived strains YG1041 and YG1042,
      respectively, allowed the detection of the presence of nitro-aromatic compounds
      in some sampling areas, which was confirmed by chemical analysis. The
      interpretation of the set of mutagenesis data suggests that there are two
      important mutagenic compound dispersion routes in the area of study: frameshift
      mutagens were dispersed predominantly by runoff and leaching, while base-pair
      substitution mutagens were dispersed mainly by the atmosphere. This mutagenic
      damage might be attributed to the effects of several substances detected in the
      area, such as aliphatic hydrocarbons and the metals aluminum, cadmium, lead and
      iron.

PMID- 19167515
TI  - Further development of the EpiDerm 3D reconstructed human skin micronucleus
      (RSMN) assay.
AB  - The upcoming ban on testing of cosmetics in animals by the European Union's 7th
      Amendment to the Cosmetics Directive will require genotoxicity safety assessments
      of cosmetics ingredients and final formulations to be based primarily on in vitro
      genotoxicity tests. The current in vitro test battery produces an unacceptably
      high rate of false positives, and used by itself would effectively prevent the
      use and development of many ingredients that are actually safe for human use. To
      address the need for an in vitro test that is more predictive of genotoxicity in
      vivo, we have developed an in vitro micronucleus assay using a three-dimensional
      human reconstructed skin model (EpiDerm) that more closely mimics the normal
      dermal exposure route of chemicals. We have refined this model and assessed its
      ability to predict genotoxicity of a battery of chemicals that have been
      previously classified as genotoxins or non-genotoxins based on in vivo rodent
      skin tests. Our reconstructed skin micronucleus assay correctly identified 7
      genotoxins and 5 non-genotoxins, demonstrating its potential to have a higher
      predictive value than currently available in vitro genotoxicity tests, and its
      utility as part of a comprehensive in vitro genotoxicity testing strategy.

PMID- 19167516
TI  - Translational regulation mechanisms of AP-1 proteins.
AB  - The activator protein 1 (AP-1) transcription factor is assembled from jun-jun,
      jun-fos, or jun-atf family protein homo- or heterodimers. AP-1 belongs to the
      class of basic leucine zipper (bZIP) transcription factors. It binds to promoters
      of its target genes in a sequence-specific manner, and transactivates or
      represses them. AP-1 proteins are implicated in the regulation of a variety of
      cellular processes including proliferation and survival, differentiation, growth,
      apoptosis, cell migration, and transformation. The decision if a given AP-1
      factor is positively or negatively regulating a specific target gene is made upon
      abundance of dimerization partners, dimer-composition, post-translational
      regulation, and interaction with accessory proteins. In this review we describe
      translational control mechanisms that can regulate the abundance of AP-1
      proteins. The Atf4/5, and JunD (mRNAs) are regulated by upORF dependent
      mechanisms. JUNB (mRNA) translation is controlled via mTOR. Translation
      efficiency of the unstable c-Fos (mRNA) can be decreased by the miRNA mir7B,
      while its perinuclear translation might facilitate efficient nuclear c-fos
      protein import. c-Jun (mRNA) appears to be regulated by both, m7G cap (CAP)
      dependent and CAP-independent translational control mechanisms, via putative
      internal ribosome entry segments (IRES). IRES elements were also proposed to play
      a role in the regulation of JunD (mRNA). We conclude that in addition to
      transcriptional and post-translational control mechanisms translational
      regulation contributes to the balanced production of AP-1 proteins, in order to
      maintain physiological cellular conditions.

PMID- 19167517
TI  - Altering the chromatin landscape for nucleotide excision repair.
AB  - DNA acts as a 'workbench' for various nuclear processes that occur inside living
      cells. In eukaryotic cells, DNA is highly compacted in a structural hierarchy
      with histones and other proteins into chromatin. This compaction affects DNA
      structure and coordinates the accessibility to site-specific nuclear factors
      during DNA processing events. DNA repair is no exception to this general rule and
      several reviews have appeared recently that discuss this topic in detail [1-3].
      Here, we focus on recent findings correlating changes in DNA repair with subtle
      variations in the chromatin landscape.

PMID- 19167518
TI  - Lipid droplets and hepatitis C virus infection.
AB  - Lipid droplets play an important part in the life cycle of hepatitis C virus and
      also are markers for steatosis, which is a common condition that arises during
      infection. These storage organelles are targeted by the viral core protein, which
      forms the capsid shell. Attachment of core to lipid droplets requires a C
      terminal domain within the protein that is highly conserved between different
      virus isolates. In infected cells, the presence of core on lipid droplets creates
      loci that contain viral RNA and non-structural proteins involved in genome
      replication. Such locations may represent sites for initiating assembly and
      production of nascent virions. In addition to utilising lipid droplets as part
      the virus life cycle, hepatitis C virus induces their accumulation in infected
      hepatocytes. The mechanisms involved in this process are not understood but
      evidence from patient-based studies and model systems suggests the involvement of
      both viral and host factors.

PMID- 19167520
TI  - Image of the month. Video imaging of inlet segment: circumferential gastric
      mucosa heterotopia in the cervical esophagus.

PMID- 19167519
TI  - Effects of co-exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and perfluorooctane
      sulfonate or perfluorooctanoic acid on expression of cytochrome P450 isoforms in
      chicken (Gallus gallus) embryo hepatocyte cultures.
AB  - In this study we investigated the effect of a single-compound exposure or two
      compound co-exposure to tetrachlorodibenzo-p-dioxin (TCDD) plus perfluorooctane
      sulfonate (PFOS) or perfluorooctanoic acid (PFOA) on the mRNA expression of
      cytochromes P450 (CYP) 1A4, 4V2 and 3A37, ethoxyresorufin-O-deethylase (EROD)
      activity and cell viability in chicken (Gallus gallus domesticus) embryo primary
      hepatocyte cultures. Cell viability after 24 h of incubation was significantly
      decreased in cells exposed to PFOS at concentrations between 30 microM and 60
      microM with or without co-exposure to TCDD (0.3 nM at maximum). PFOA did not
      decrease cell viability even at maximum concentrations of 60 microM. TCDD induced
      CYP1A4 mRNA and EROD activity substantially as reported previously. PFOS also
      increased CYP1A4 mRNA in a concentration-dependent manner. Co-exposure of cells
      to PFOS plus TCDD did not change CYP1A4 mRNA levels compared to cells treated
      with TCDD alone. PFOS alone did not induce CYP4V2 mRNA, however 40-50 microM PFOS
      plus TCDD (0.3 nM) induced CYP4V2 mRNA compared to TCDD alone (P<0.05). This
      trend was similar to that observed with co-exposure to TCDD plus PFOA, suggesting
      that PFOA alone did not induce CYP4V2 mRNA, whereas co-exposure to TCDD plus PFOA
      induced the expression levels. PFOS alone decreased CYP3A37 mRNA by a maximum of
      45%, however after co-exposure to TCDD, recovery of mRNA expression to levels
      measured in DMSO-treated cells was observed. Our data suggest a complex gene
      response to mixtures of dioxin-like and perfluorinated compounds.

PMID- 19167521
TI  - Enterolith: a diagnostic clue for intestinal stricture.

PMID- 19167522
TI  - Not all side effects associated with tricyclic antidepressant therapy are true
      side effects.
AB  - BACKGROUND & AIMS: Patients with functional gastrointestinal disorders treated
      with tricyclic antidepressants sometimes report nongastrointestinal symptoms; it
      is unclear whether these are drug side effects or reflect a behavioral tendency
      to report symptoms. We evaluated whether symptoms reported before treatment with
      a tricyclic antidepressant (desipramine) increased in number or worsened in
      severity after 2 weeks of treatment and assessed the baseline factors that
      predispose patients to report symptoms. METHODS: Female patients in a multicenter
      National Institutes of Health trial for functional bowel disorders completed a 15
      item symptom questionnaire at baseline (before randomization), 2 weeks after they
      were given desipramine (n = 81) or placebo (n = 40), and at study completion (12
      weeks). Patients were asked about the severity and frequency of 15 symptoms.
      Results were analyzed from 57 patients given desipramine who completed the
      questionnaires. RESULTS: Symptoms reported as side effects to have occurred more
      frequently and also worsened at week 2 in the group given desipramine included
      dizziness, dry mouth/thirstiness, lightheadedness, jittery feelings/tremors, and
      flushing. Symptoms that did not change in severity or showed improvement at week
      2 in the group given desipramine included morning tiredness, nausea, blurred
      vision, headaches, appetite reduction, and trouble sleeping. Psychologic distress
      but not desipramine blood level correlated with symptom reporting. CONCLUSIONS:
      Most symptoms often attributed to side effects of desipramine were present before
      treatment; only a few, related to anticholinergic effects, worsened 2 weeks after
      treatment, suggesting that most so-called side effects were not associated
      specifically with desipramine use. Such symptoms might instead be associated with
      psychologic distress.

PMID- 19167524
TI  - Clinic and pathophysiology of photosensitivity in lupus erythematosus.
AB  - Lupus erythematosus (LE) represents an autoimmune disease with great clinical
      variability in which photosensitivity is a common feature for all forms and
      subsets. The nature and characteristics of clinical photosensitivity in LE have
      been elucidated through standardized phototesting procedures. The development of
      skin lesions after UV-injury is typically delayed starting from a few days up to
      three weeks after the irradiation, and may persist for months. Therefore,
      patients may not be aware of the detrimental effects of sunlight for their
      disease. The most photosensitive subset of LE is LE tumidus, followed by subacute
      cutaneous LE. Phototesting has also been crucial for studying the pathophysiology
      of LE-photosensitivity. Abnormalities of generation and clearance of UV-triggered
      apoptotic cells in LE are an important source of autoantigens. Recent data
      demonstrate the linkage of innate with adoptive immune pathways in UV-induced
      autoimmune response. Plasmocytoid dendritic cells (PDC) and their secreted IFN
      alpha play a central role in the LE-pathogenesis. The recruitment of relevant
      leukocyte subsets is dependant on certain chemokines, which have been
      characterized in recent studies. An amplification cycle has been postulated, in
      which UV induces apoptosis and necrosis resulting in the production and release
      of chemokines. Subsequently, effector memory T cells as well as PDCs are
      recruited and activated perpetuating an amplification process that leads to UV
      induced cutaneous LE lesion.

PMID- 19167523
TI  - Aberrant Epstein-Barr viral infection in systemic lupus erythematosus.
AB  - Serologic association, cross-reactivity of select EBV-specific antibodies with
      SLE autoantigens, SLE-like autoimmunity after immunization with EBV peptides,
      increased EB viral load in SLE patients, and SLE-specific alterations in EBV
      humoral and cellular immunity implicate Epstein-Barr virus (EBV) in the
      development of systemic lupus erythematosus (SLE). To investigate SLE-specific
      differences in EBV gene expression, levels of eight EBV genes were compared
      between SLE patients and controls by using both ex vivo-infected and un
      manipulated peripheral blood mononuclear cells (PBMCs). Expression levels of mRNA
      were significantly greater by Wilcoxen signed rank test in the ex vivo-infected
      SLE patient-derived cells for 4 of 8 EBV genes, including BLLF1, 3.2-fold
      (p<0.004); LMP-2, 1.7-fold (p<0.008); EBNA-1, 1.7-fold (p<0.01); and BcRF1, a
      proposed DNA binding protein, 1.7-fold (p<0.02). The frequency of LMP-1 gene
      expression was significantly greater by Chi square analysis in the peripheral
      blood from SLE patients than controls (44% of patients, 10% of controls p<0.05).
      PBMCs from SLE patients had greater expression of latent genes as well as
      increased expression of both latent and lytic genes after infection, suggesting
      that EBV may participate in SLE etiology through several mechanisms. Such altered
      infection patterns may contribute to the increased levels of EBV and the
      molecular mimicry seen in sera from SLE patients.

PMID- 19167525
TI  - Conformational and biochemical characterization of a biologically active rat
      recombinant Protease Nexin-1 expressed in E. coli.
AB  - Protease Nexin-1, a 43-kDa glycoprotein, is a major physiological thrombin
      inhibitor involved in the modulation of nerve cell plasticity. Recombinant rat
      Protease Nexin-1 (rPN-1) was efficiently produced in Escherichia coli using a T7
      RNA polymerase based expression system and purified by heparin-sepharose affinity
      chromatography yielding 3 mg of protein per liter of cell culture. The purity and
      chemical identity of rPN-1 were assessed by SDS-PAGE, Reverse Phase- High
      Performance Liquid Chromatography, mass spectrometry and two-dimensional-gel
      electrophoresis. Conformational analysis by circular dichroism and fluorescence
      spectroscopy revealed the presence of mixed alpha/beta secondary structure and
      the prevailing localization of Trp-residues in rather polar environments.
      Fluorescence titration of rPN-1 with heparin indicated that rPN-1 binds heparin
      with high affinity. Furthermore, the formation of a SDS-stable 1:1 thrombin-rPN-1
      complex, monitored by SDS-PAGE, confirmed the native-like structure of rPN-1.
      Finally, the cellular effects of rPN-1, such as its ability to promote neurite
      outgrowth in neuroblastoma cells, were found to be very similar to those elicited
      by natural PN-1. Altogether, our results demonstrate that glycosylation does not
      alter neither structure nor function of PN-1 and that E. coli is a suitable
      expression system for obtaining milligram quantities of pure and fully active rPN
      1 for structural and functional studies.

PMID- 19167526
TI  - EmrE, a model for studying evolution and mechanism of ion-coupled transporters.
AB  - EmrE is a small (110 residues) SMR transporter from Escherichia coli that
      extrudes positively charged aromatic drugs in exchange for two protons, thus
      rendering bacteria resistant to a variety of toxic compounds. Due to its size,
      stability and retention of its function upon solubilization in detergent, EmrE
      provides a unique experimental paradigm for the biochemical and biophysical
      studies of membrane based ion-coupled transporters. In addition, EmrE has been in
      center stage in the past two years because it provides also a paradigm for the
      study of the evolution of membrane proteins. Controversy around this topic is
      still going on and some novel concepts are surfacing that may contribute to our
      understanding of evolution of topology of membrane proteins. Furthermore, based
      on the findings that the cell multidrug transporters interact functionally we
      introduce the concept of a cell Resistosome.

PMID- 19167527
TI  - Molecular interaction between apo or holo alpha-lactalbumin and lysozyme:
      formation of heterodimers as assessed by fluorescence measurements.
AB  - In a previous work, we reported that contrary to native calcium-loaded alpha
      lactalbumin (holo alpha-LA), calcium-depleted form (apo alpha-LA) has the ability
      to self-assemble with lysozyme (LYS) to form different supramolecular structures
      in temperature-dependent manner. In this study, we examine what happens at
      molecular scale using fluorescence techniques. Fluorescence anisotropy coupled
      with fluorescence lifetime measurements provides a means to measure
      intermolecular interactions. We showed that LYS interacts with both apo alpha-LA
      and holo alpha-LA to form oligomers, assumed to be heterodimers, at 10 degrees C
      and 45 degrees C. The dissociation constants for dimerization were found to be in
      the muM range and increased significantly with increasing ionic strength from 39
      to 124 mM. Although the binding constants of holo alpha-LA-LYS and apo alpha-LA
      LYS complexes were of the same order of magnitude, the shape or conformation of
      formed heterodimers differed as assessed by fluorescence parameters in particular
      correlation time calculations. Such conformation differences could explain why
      holo alpha-LA-LYS complexes are trapped as heterodimers while the apo alpha-LA
      LYS complexes have the ability to further self-assemble into various
      supramolecular structures.

PMID- 19167529
TI  - Improving mass measurement accuracy in mass spectrometry based proteomics by
      combining open source tools for chromatographic alignment and internal
      calibration.
AB  - Accurate mass determination enhances peptide identification in mass spectrometry
      based proteomics. We here describe the combination of two previously published
      open source software tools to improve mass measurement accuracy in Fourier
      transform ion cyclotron resonance mass spectrometry (FTICRMS). The first program,
      msalign, aligns one MS/MS dataset with one FTICRMS dataset. The second software,
      recal2, uses peptides identified from the MS/MS data for automated internal
      calibration of the FTICR spectra, resulting in sub-ppm mass measurement errors.

PMID- 19167528
TI  - Tools for exploring the proteomosphere.
AB  - Homology-driven proteomics aims at exploring the proteomes of organisms with
      unsequenced genomes that, despite rapid genomic sequencing progress, still
      represent the overwhelming majority of species in the biosphere. Methodologies
      have been developed to enable automated LC-MS/MS identifications of unknown
      proteins, which rely on the sequence similarity between the fragmented peptides
      and reference database sequences from phylogenetically related species. However,
      because full sequences of matched proteins are not available and matching
      specificity is reduced, estimating protein abundances should become the
      obligatory element of homology-driven proteomics pipelines to circumvent the
      interpretation bias towards proteins from evolutionary conserved families.

PMID- 19167530
TI  - Differential CpG island methylation of murine adenine nucleotide translocase
      genes.
AB  - Adenine nucleotide translocase (Ant) mediates the exchange of ADP and ATP across
      the inner mitochondrial membrane in eukaryotes. Mice possess three distinct but
      highly homologous Ant isoforms, encoded by independent genes, whose transcription
      depends upon tissue type. Ant1 is expressed selectively in heart and skeletal
      muscles, Ant2 is ubiquitously expressed in most tissues but lower in skeletal
      muscle and testis, while Ant4 is exclusively expressed in the testis. Of
      interest, each of these Ant genes contains CpG islands in their proximal promoter
      regions. We investigated the methylation status of the three Ant genes in various
      tissues with active and inactive transcription. In contrast to the Ant4 gene in
      which CpG island methylation is essential for gene repression, the CpG islands of
      Ant1 and Ant2 are hypomethylated regardless of the gene expression status
      throughout the tissues of male mice. Despite the tissue specific expression
      profile of Ant1, CpG methylation is unlikely involved in the regulation of the
      gene. Consistent with these findings, addition of a CpG-demethylating agent, 5
      aza-2'-deoxycitidine, to fibroblasts increased the expression of Ant4 but not
      Ant1 or Ant2 genes. This study provides insight regarding the differential
      regulation of Ant isoforms in mammals, whereby both the Ant1 and Ant2 genes are
      capable of expression, but the Ant4 gene is completely repressed throughout
      somatic tissues. To the best of our knowledge, this is a first example to clearly
      demonstrate a differential usage of CpG island methylation within a family of
      genes.

PMID- 19167531
TI  - Identification and association analysis of single nucleotide polymorphisms in the
      human noggin (NOG) gene and osteoporosis phenotypes.
AB  - Noggin, an extracellular bone morphogenic protein (BMP) antagonist, blocks BMP
      signaling and decreases osteoblastogenesis. The purpose of this study was to
      identify novel sequence variations in the human noggin gene and to perform
      association analyses of these variations with phenotypes related to osteoporosis.
      Novel single nucleotide polymorphisms (SNPs) were identified by resequencing 7 kb
      of the noggin gene region in 24 randomly selected Afro-Caribbean men without
      regard to their bone mineral density (BMD) level. We identified 22 SNPs in the 7
      kb noggin gene region, only 2 of which were previously described in dbSNP (build
      126). There were also 11 unvalidated SNPs from dbSNP that could not be verified
      in our sequence analysis. Ten of the 22 identified SNPs showed a minor allele
      frequency greater than 0.05. Seven of these common SNPs were genotyped in 2060
      Afro-Caribbean men age 40 and older. None of the 7 SNPs were associated with BMD
      at the proximal femur or lumbar spine. Our analysis suggests that a common
      variation in the noggin gene is unlikely to have a major impact on BMD among
      older men of African ancestry.

PMID- 19167532
TI  - Prosthodontic treatment considerations for patients with oral sinonasal mucosal
      malignant melanoma: a clinical report.
AB  - Patients with a diagnosis of mucosal malignant melanoma involving the maxilla or
      paranasal sinuses requiring surgery are referred to the maxillofacial
      prosthodontist for treatment. The standard protocol of surgical, interim, and
      definitive obturator treatment is usually anticipated. Depending upon the stage
      and presence or absence of metastasis, it is generally accepted that the
      prognosis for cure of this disease is poor. This clinical report reviews the
      current literature regarding treatment and the overall guarded prognosis for this
      disease, and reports the prosthodontic treatment intervention for 8 patients.
      Prosthodontic treatment strategies are recommended that are consistent with the
      reality of the diagnosis to achieve optimal function and quality of life for
      these patients.

PMID- 19167533
TI  - In vitro comparison of visual and computer-aided pre- and post-tooth shade
      determination using various home bleaching procedures.
AB  - STATEMENT OF PROBLEM: Due to inter- and intraexaminer differences, subjective
      evaluation of tooth color is deemed problematic. PURPOSE: The purpose of this
      study was to evaluate the efficacy of home bleaching products, and to compare
      visual and computer-aided tooth shade determinations when various agents were
      applied. MATERIAL AND METHODS: Human incisors (n=288) were stained (red wine,
      black tea) and allocated to 8 groups (n=36). Paint-on varnish (VivaStyle Paint
      On; 6% carbamide peroxide, CP) was used either for 1 x 20 min/d (VSP1), 2 x 20
      min/d (VSP2), or 2 x 5 min/d (VSP25). Paint-on lacquer (Colgate Simply White,
      CSW; 5.9% hydrogen peroxide, HP) was applied for 2 x 30 min/d. Moreover,
      bleaching was performed using trays (VivaStyle, VS; 10% CP; 1 x 60 min/d, and
      Odol-med3 Beauty Kur, OBK; sodium chlorite; 2 x 10 min/d) or whitening strips
      (blend-a-med Whitestrips, BWS; 5.9% HP; 2 x 30 min/d). Water was used as control
      (1 x 60 min/d). Tooth shades were determined blindly (Chromascop Complete) after
      staining and 24 hours after final bleaching (visual and computer-aided
      assessment). Change in shade was analyzed using nonparametric methods (Kruskal
      Wallis) and post hoc tests (Tukey and Kramer) (alpha=.05). RESULTS: Color changed
      significantly to lighter shades for all active agents. Analysis revealed
      significant differences among the control and all other groups, and among CSW/BWS
      versus VSP25/OBK, and VS versus OBK, for both evaluation methods. Additionally,
      significant differences were spectrophotometrically observed for VSP1/VSP2 versus
      BWS, and VSP2 versus OBK, with comparable reliabilities (0.995 at baseline; 0.994
      after bleaching). CONCLUSIONS: Increased bleaching efficacy was observed with
      high peroxide concentrations; application time did not alter efficacy.
      Spectrophotometry was reproducible and objective. The 2 assessment methods
      matched 45.8% of the time.

PMID- 19167534
TI  - The effects of laser etching on shear bond strength at the titanium ceramic
      interface.
AB  - STATEMENT OF PROBLEM: The use of titanium has increased for metal ceramic
      restorations, as well as for use in titanium implants, with developments in
      CAD/CAM technology. Some surface treatments of titanium have been introduced to
      enhance the titanium bond strength to low-fusing porcelains; however, a more
      reliable, easily used dental laboratory method has not been established. PURPOSE:
      The purpose of this study was to compare the effect of laser etching as a
      titanium surface treatment with 3 other surface treatments (machining, airborne
      particle abrasion, and acid etching), evaluating their ability to enhance the
      bond strength between a titanium substrate and porcelain. MATERIAL AND METHODS: A
      total of 64 specimen rods of commercially pure titanium (ASTM grade 2, 20 mm in
      length and 5.7 mm in diameter) were divided into 4 experimental groups (n=16) to
      receive different surface treatments: machined with no treatment (MS), airborne
      particle abraded with alumina particles (250 microm) (APAS), acid etched with 10%
      HCl (AES), and laser etched (LES) using a neodymium-doped yttrium aluminum garnet
      laser (Nd:Y(3)AL(5)O(12), or Nd/YAG). Low-fusing porcelain (Triceram) was applied
      (4-mm thickness) to the treated titanium surfaces and fired. Shear bond strength
      testing was performed in a universal testing machine. All of the data were
      compared using 1-way ANOVA and the post hoc multiple range Tukey test
      (alpha=.05). Measurement of roughness (Ra value) and SEM analysis were also
      performed for 1 specimen of each group before and after the shear bond strength
      test to evaluate the nature of the fracture surface. RESULTS: Shear bond strength
      values for the APAS group (22.22 (4.04) MPa) and the LES group (21.22 (3.41) MPa)
      were significantly greater (P<.05) than for the MS group (13.76 (3.16) MPa) and
      the AES group (14.98 (3.26) MPa). The SEM image after debonding of MS and AES
      showed porcelain retained on the surface. However, there was no difference in
      appearance between the APAS and LES before and after debonding. CONCLUSIONS:
      Laser etching of titanium surfaces using an Nd/YAG laser was effective in
      improving bond strength with low-fusing porcelain, as compared to the acid
      etching method. However, there was no significant difference between laser
      etching and airborne-particle-abrasion surface treatment.

PMID- 19167535
TI  - Tensile bond strength of an adhesive resin cement to different alloys having
      various surface treatments.
AB  - STATEMENT OF PROBLEM: The ability of a resin cement to bond to a restorative
      alloy is critical for maximal crown retention to nonideal preparations. Surface
      treatment and metal type may have an important role in optimizing resin-to-metal
      strength. PURPOSE: The purpose of this study was to examine the effect of surface
      pretreatment on the tensile strength of base and noble metals bonded using a
      conventional resin cement. MATERIAL AND METHODS: Cylindrical plastic rods (9.5 mm
      in diameter), cast in base (Rexillium NBF) or noble metal (IPS d.SIGN 53), were
      divided into rods 10 mm in length (n=10-12). Specimens were heated in a porcelain
      furnace to create an oxide layer. Test specimens were further subjected to
      airborne-particle abrasion (50-microm Al(2)O(3) particles) alone or with the
      application of a metal primer (Alloy Primer). Similarly treated rod ends were
      joined using resin cement (RelyX ARC), thermocycled (x500, 5 degrees -55 degrees
      C) and stored (24 hours, 37 degrees C) before debonding using a universal testing
      machine. Debond strength and failure site were recorded. Rank-based ANOVA for
      unbalanced designs was used to test for significant interaction (alpha=.050).
      Each pair of treatments was compared separately for each metal (Bonferroni
      adjusted significance level of .0083, overall error rate for comparisons, .05).
      The 2 metals were compared separately for each of the 3 treatments using an
      adjusted significance level of .017, maintaining an overall error rate of .05. A
      multinomial logit model was used to describe the effect of metal type and surface
      pretreatment on failure site location (alpha=.05). RESULTS: Interaction between
      metal type and surface pretreatment was significant for stress values (P=.019).
      Metal type did not significantly affect tensile bond strength for any of the
      compared surface pretreatments. Metal primer significantly improved tensile bond
      strength for each metal type. Most failures tended to occur as either adhesive or
      mixed in nature. CONCLUSIONS: Metal primer application significantly enhanced
      tensile bond strength to base and noble metal. No significant differences in
      tensile strength were found between alloys. Differences in failure site incidence
      were found to be related to metal type and surface pretreatment.

PMID- 19167536
TI  - The influence of veneering porcelain thickness of all-ceramic and metal ceramic
      crowns on failure resistance after cyclic loading.
AB  - STATEMENT OF PROBLEM: In some clinical situations, the length of either a
      prepared tooth or an implant abutment is shorter than ideal, and the thickness of
      a porcelain crown must be increased. Thickness of the coping and the veneering
      porcelain should be considered to prevent mechanical failure of the crown.
      PURPOSE: The purpose of this study was to investigate the influence of veneering
      porcelain thickness for all-ceramic and metal ceramic crowns on failure
      resistance after cyclic loading. MATERIAL AND METHODS: All-ceramic and metal
      ceramic crowns (n=20) were fabricated on an implant abutment (RN Solid Abutment)
      for the study. Two different framework designs with 2 different incisal
      thicknesses of veneering porcelain (2 mm and 4 mm) were used for each all-ceramic
      and metal ceramic crown system, resulting in 4 experimental groups (n=10) with
      identically shaped crowns. The all-ceramic crown consisted of alumina (Procera
      AllCeram) frameworks and veneering porcelain (Cerabien), while metal ceramic
      crowns were made of high noble metal (Leo) frameworks and veneering porcelain
      (IPS Classic). All crowns were cemented on the corresponding abutments using a
      resin cement (Panavia 21). They were subjected to 1000 cycles of thermal cycling
      (5 degrees C and 55 degrees C; 5-second dwell time). The crowns were tested with
      a custom-designed cyclic loading apparatus which delivered simultaneous
      unidirectional cyclic loading at 135 degrees, vertically, at an rpm of 250, with
      a load of 49 N. Each specimen was loaded for 1.2 x 106 cycles or until it failed.
      The specimens were thoroughly evaluated for cracks and/or bulk fracture with an
      optical stereomicroscope (x10) and assigned a score of success, survival, or
      failure. The specimens without bulk fracture after cyclic loading were loaded
      along the long axis of the tooth, on the incisal edge, in a universal testing
      machine at a crosshead speed of 1.5 mm/min, until fracture. Fisher's exact test
      was used to compare the success and survival rate between the 2 different
      materials (alpha=.05). Two-way ANOVA was used to analyze data in terms of
      material, porcelain thickness, and interaction effect. Also, a 2-sample t test
      was performed to compare between 2 thicknesses within the same material
      (alpha=.05). RESULTS: According to the Fisher's exact test, the all-ceramic group
      showed significantly higher success (P=.003) and survival rates (P=.001) than the
      metal ceramic group. For the failure load, the 2-way ANOVA showed significant
      effects for material (P<.001) and porcelain thickness (P=.004), but not a
      significant interaction effect (P=.198). For the metal ceramic groups, crowns
      with a 2-mm porcelain thickness showed a significantly greater failure load than
      crowns with a 4-mm porcelain thickness (P=.004). However, all-ceramic groups did
      not show a significant difference between the 2 different thicknesses of
      veneering porcelain (P=.198). CONCLUSIONS: The all-ceramic crowns showed
      significantly higher success and survival rates after cyclic loading, but lower
      failure loads than metal ceramic crowns. The thickness of the veneering porcelain
      affected the failure load of the metal ceramic crowns, but not that of the all
      ceramic crowns.

PMID- 19167537
TI  - Kinetic analysis of monomer conversion in auto- and dual-polymerizing modes of
      commercial resin luting cements.
AB  - STATEMENT OF PROBLEM: Lack of knowledge regarding the kinetics of the setting
      reaction of dual- and autopolymerizing resin luting agents (RLA) leads the
      clinician to underestimate the care required during occlusal adjustments of
      indirect restorations. PURPOSE: The purpose of this study was to evaluate the
      degree of conversion (DC), maximum rate of polymerization (R(p)(max)), and
      potential of cure (ratio of conversions in autopolymerized relative to dual
      polymerized modes; PC(A/D)) of 5 dual-polymerizable RLAs at 5 and 10 minutes,
      after mixing RLA components using infrared (IR) spectroscopy. MATERIAL AND
      METHODS: The RLAs evaluated included Calibra, Duo-Link, Lute-It, Nexus 2, and
      RelyX ARC. The RLAs were manipulated and applied to the horizontal diamond
      element in the optical bench of an IR spectrometer. The materials were either
      light activated for 40 seconds (dual-polymerizing mode) or were allowed to
      autopolymerize (autopolymerizing mode). The DC, R(p)(max), and PC(A/D) were
      calculated using standard techniques of observing changes in aliphatic-to
      aromatic peak ratios before and after polymerization. Data (n=5) were analyzed by
      2-way repeated measures ANOVA and Tukey's post hoc test (alpha=.05). RESULTS: All
      autopolymerizing groups exhibited lower DC and R(p)(max) values than the dual
      polymerizing groups (P<.001), and higher DC values at 10 minutes than at 5
      minutes, only in the autopolymerizing mode. Duo-Link exhibited the highest
      R(p)(max) values among dual-polymerizing groups, while Lute-It and Calibra showed
      the lowest R(p)(max) values and the highest PC(A/D) values. Within
      autopolymerizing groups, Nexus 2 and Lute-It exhibited the highest R(p)(max)
      values, while RelyX ARC demonstrated the lowest R(p)(max) as well as the lowest
      PC(A/D) values. CONCLUSIONS: The DC values of all autopolymerized groups of RLAs
      were lower than those of the dual-polymerized RLAs, but the differences in
      R(p)(max) and PC(A/D) were product dependent. The DC of all products was higher
      at the 10-minute interval than at the 5-minute interval, only in the
      autopolymerizing mode.

PMID- 19167538
TI  - Diagnosing denture problems using pressure-indicating media.
AB  - Pressure-indicating media have more diverse applications than merely the
      identification of areas on the denture base that cause mucosal pressure and pain.
      The purpose of this article is to provide guidelines for optimal use of the media
      and to identify alternative uses that could be considered in daily practice.

PMID- 19167539
TI  - Repair procedure for partially separated polyurethane-lined facial prosthesis.

PMID- 19167540
TI  - The use of vacuum-formed plastic sheets to create reservoir space for fluoride
      trays.

PMID- 19167541
TI  - Stabilizing existing removable partial prostheses during impression procedures.

PMID- 19167542
TI  - Stabilizing uncemented fixed prostheses during transfer impressions.

PMID- 19167543
TI  - Evidence-based practice. Preface.

PMID- 19167544
TI  - Evidence Equals Excellence: The application of an evidence-based practice model
      in an academic medical center.
AB  - An evidence-based practice (EBP) program that is designed to develop mentors in
      both clinical and academic settings has the potential for transforming a health
      care organization. This article describes an innovative program, Evidence Equals
      Excellence, which consists of two components: a clinical practice component for
      health care clinicians and an academic program for baccalaureate and graduate
      nursing students. The development of EBP mentors creates a core group of
      clinicians who can assist fellow staff members apply evidence at the bedside. An
      academic program prepares new graduates to partner easily with clinical mentors
      to support and initiate successful practice changes.

PMID- 19167545
TI  - A collaborative approach to building the capacity for research and evidence-based
      practice in community hospitals.
AB  - The use of best evidence to support nursing practice and the generation of new
      knowledge to use in practice are hallmarks of excellence. Nurses at the bedside,
      however, often lack the resources and knowledge necessary to change the
      traditional nursing culture to one in which the use of evidence is incorporated
      into daily care. This article describes the experience in two hospitals using a
      program designed to give nurses the skills needed to engage in evidence-based
      care.

PMID- 19167546
TI  - Development of an evidence-based practice and research collaborative among urban
      hospitals.
AB  - This article describes the development of an evidence-based practice and research
      collaborative among urban hospitals. The collaborative began as a mechanism to
      support the incorporation of evidence-based practice and research in the acute
      care practice setting. This article discusses the development of the
      collaborative, as well as the challenges, success, and future goals from both the
      academic and practice perspectives.

PMID- 19167547
TI  - Renewing the spirit of nursing: Embracing evidence-based practice in a rural
      state.
AB  - A group of nursing leaders from several organizations in the central and northern
      regions of the state established the Maine Nursing Practice Consortium (MNPC).
      The MNPC has created educational opportunities through workshops that assist
      nurses with the development and implementation of evidence-based practice (EBP)
      in rural Maine. Through collaboration and consultation with EBP leaders, members
      have ignited a spirit of inquiry and gained the support of nurses from varied
      backgrounds to engage actively in EBP initiatives. This article briefly
      summarizes the process of establishing these collaborative partnerships,
      describes some of the outcomes from the workshops, and describes the
      organizational and individual commitment that was essential to the work.

PMID- 19167548
TI  - Implementing a health system-wide evidence-based practice educational program to
      reach nurses with various levels of experience and educational preparation.
AB  - This article describes a system-wide evidence-based practice (EBP) educational
      initiative implemented with a geographically, educationally, and clinically
      diverse group of nurses with the intent of increasing their EBP skill set and
      efficacy as local change agents and leaders. The overall scope of the larger
      National Quality Forum Scholar Program is described, and then the focus is
      narrowed to describe the EBP components of the initiative with case examples and
      lessons learned.

PMID- 19167549
TI  - Promotion of safe outcomes: Incorporating evidence into policies and procedures.
AB  - This article describes the process of incorporating evidence into policies and
      procedures, resulting in the establishment of evidence as a basis for safe
      practice. The process described includes use of the Rosswurm and Larrabee model
      for change to evidence-based practice. The model guided the work of evidence
      based practice mentors in developing a template, system, and educational plan for
      dissemination of evidence-based policies and procedures into patient care.

PMID- 19167550
TI  - Staff nurses creating safe passage with evidence-based practice.
AB  - Patient safety is one of the most critical issues for health care today. The
      escalating need to decrease preventable complications serves as a significant
      catalyst to identify and use evidence-based practice (EBP) at the bedside.
      Decreasing preventable complications requires a synergistic relationship between
      the nurses at the bedside and nursing leadership. This article presents an
      overview of the concepts and the specific structures and processes used at Baylor
      Health Care System to increase the use of EBP and improve patient safety.

PMID- 19167551
TI  - A nursing quality program driven by evidence-based practice.
AB  - St. Luke's Episcopal Hospital in Houston established a best-practice council as a
      strategy to link nursing quality to evidence-based practice. Replacing a system
      based on reporting quality control and compliance, this Best Practice Council
      formed interdisciplinary teams, charged them each with a quality issue, and
      directed them to change practice as needed under the guidance of the St. Luke's
      Episcopal Hospital Evidence Based Practice Model. This article reviews the
      activities of the Best Practice Council and the projects of teams assigned to
      study best practice in (1) preventing bloodstream infection (related to central
      lines), (2) preventing patient falls, (3) assessing and preventing pressure
      ulcers, and (4) ensuring good hand-off communication.

PMID- 19167552
TI  - Development and implementation of an inductive model for evidence-based practice:
      A grassroots approach for building evidence-based practice capacity in staff
      nurses.
AB  - Evidence-based practice (EBP) is an essential component of the development of
      nursing science and has importance for today's clinical nurses. It benefits
      patients, organizations, and the nursing discipline, as well as having personal
      and professional benefits for individual clinicians. As interest in EBP has
      grown, so has the need for educational programs designed to develop the scholarly
      skills of the nursing workforce. The Clinical Scholar Model is one grassroots
      approach to developing a cadre of clinical nurses who have the EBP and research
      skills necessary in today's demanding health care delivery environments.

PMID- 19167553
TI  - Effect of a preoperative instructional digital video disc on patient knowledge
      and preparedness for engaging in postoperative care activities.
AB  - This project determined the effects of developing and implementing a preoperative
      instructional digital video disc (DVD) on patients' level of knowledge,
      preparedness, and perceived ability to participate in postoperative care
      activities. Content areas that were incorporated into the preoperative
      instructional DVD included: pain management, surgical drainage, vital signs,
      incentive spirometry, cough and deep breathe, chest physiotherapy, anti-embolism
      stockings/sequential compression device, ambulation, diet/bowel activity/urine
      output, and discharge. A system was created to ensure that patients consistently
      received the preoperative instructional DVD prior to surgery. The instructional
      media product was found to be effective in increasing pre-operative knowledge and
      preparedness of patients and their families. Nurses reported higher levels of
      knowledge and engagement among patients and their families related to
      postoperative activities.

PMID- 19167554
TI  - The Clinical Scholar Model: Evidence-based practice at the bedside.
AB  - The Clinical Scholar Model serves as an effective framework for investigating and
      implementing evidence-based practice (EBP) changes by direct care providers. The
      model guides one in identifying problems and issues, key stakeholders, and the
      need for practice changes. It provides a framework to critique and synthesize the
      external and internal evidence. Three EBP projects conducted at a large tertiary
      care facility in northern New England illustrate the process of using the
      Clinical Scholar Model.

PMID- 19167555
TI  - Using evidence to improve care for the vulnerable neonatal population.
AB  - The facilitation of evidence-based practice (EBP) in the clinical setting is
      important to ensure patients receive the best care possible. This article
      highlights changes in open visitation and feeding readiness practices that
      occurred in a Magnet-designated facility neonatal ICU. The examples demonstrate
      ways to bring evidence to the bedside within an environment that supports EBP at
      all levels of nursing leadership.

PMID- 19167556
TI  - From the bedside to the boardroom: Resuscitating the use of nursing research.
AB  - This article describes the process used by a multi-institutional organization to
      engage nurses in using and conducting nursing research using the Clinical Scholar
      Model. The challenges faced on the journey to engage nurses in questioning their
      practice and searching for answers are highlighted. Key resources necessary for a
      successful outcome are identified.

PMID- 19167557
TI  - A dismal year for human rights abuses.

PMID- 19167558
TI  - Investment in health systems--a priority for health and wealth.

PMID- 19167559
TI  - A NICE adaptation.

PMID- 19167560
TI  - Intimate-partner violence and fetal loss.

PMID- 19167561
TI  - Reforming China's health care: for the people, by the people?

PMID- 19167563
TI  - Barbara Hogan: South Africa's Minister of Health.

PMID- 19167564
TI  - Neglected tropical diseases and the Global Fund.

PMID- 19167565
TI  - Alma-Ata addresses cultural, economic, and political issues too.

PMID- 19167566
TI  - Governments, civil society, and social determinants of health.

PMID- 19167567
TI  - Bias in WHO report on the social determinants of health.

PMID- 19167568
TI  - Green space, psychological restoration, and telomere length.

PMID- 19167569
TI  - Health-care equity--for all generations?

PMID- 19167570
TI  - 2009: a crucial year for progress on the health workforce crisis.

PMID- 19167571
TI  - Spousal violence and potentially preventable single and recurrent spontaneous
      fetal loss in an African setting: cross-sectional study.
AB  - BACKGROUND: Spousal violence is a global issue, with ramifications for the
      reproductive health of women. We aimed to investigate the effect of physical,
      sexual, and emotional violence on potentially preventable single and recurrent
      spontaneous fetal loss. METHODS: We analysed data from the Cameroon Demographic
      Health Survey. In the violence module of this survey, women were questioned about
      their experience of physical, emotional, and sexual violence inflicted by their
      spouses. Respondents were also asked about any stillbirths and spontaneous
      abortions. We measured risk for single and recurrent fetal loss with odds ratios,
      with adjustment for intracluster correlations as appropriate. We also estimated
      the proportion of preventable excess fetal loss at various levels of violence
      reduction. FINDINGS: 2562 women responded to the violence module. Those exposed
      to spousal violence (n=1307) were 50% more likely to experience at least one
      episode of fetal loss compared with women not exposed to abuse (odds ratio 1.5;
      95% CI 1.3-1.8). Recurrent fetal mortality was associated with all forms of
      spousal violence, but emotional violence had the strongest association (1.7; 1.2
      2.3). If the prevalence of spousal abuse could be reduced to 50%, 25%, or
      entirely eliminated, preventable excess recurrent fetal demise would be 17%, 25%,
      and 33%, respectively. INTERPRETATION: Spousal violence increases the likelihood
      of single and repeated fetal loss. A large proportion of risk for recurrent fetal
      mortality is attributable to spousal violence and, therefore, is potentially
      preventable. Our findings support the idea of routine prenatal screening for
      spousal violence in the African setting, a region with the highest rate of fetal
      death in the world.

PMID- 19167572
TI  - Medical ethics and torture: revising the Declaration of Tokyo.

PMID- 19167573
TI  - Health systems, health, and wealth: a European perspective.

PMID- 19167574
TI  - Amnesia, political ambition, and canned tuna.

PMID- 19167575
TI  - Hematologic Issues. Introduction.

PMID- 19167576
TI  - The CBC: reference ranges for neonates.
AB  - "Normal values" for blood parameters of neonates are generally unavailable,
      because blood is not usually drawn on healthy, normal neonates to establish
      normal ranges. Instead, "reference ranges" are used, consisting of the 5th to the
      95th percentile values compiled from tests performed on neonatal patients with
      minimal pathology, under the premise that such ranges approximate normal values.
      In recent years, we have been seeking to establish reference ranges for various
      elements of the complete blood count (CBC) of neonates, using the large databases
      of Intermountain Healthcare, a health care system in the western United States.
      Establishing these reference ranges has been facilitated by using modern
      hematology analyzers and electronic data repositories of clinical and laboratory
      information. The present review brings together several of our recent reports,
      displaying reference ranges for elements of the CBC among neonates at various
      gestational and postnatal ages.

PMID- 19167578
TI  - Congenital cytopenias and bone marrow failure syndromes.
AB  - Congenital bone marrow failure syndromes (CBMFS) are extremely uncommon diseases
      that can present in the neonate. The objective of this article is to review the
      presentation, diagnosis, pathophysiology, and management of CBMFS in relation to
      neonatology. CBMFS should be considered when a single or multiple blood cell
      lineages are low secondary to failure of production. Diagnosis in the neonatal
      period requires a high index of suspicion. In this particular age group, CBMFS
      should be considered when the neonate has a family history of CBMFS, is small for
      gestational age, or has other physical abnormalities. History and physical
      examination can lead to the diagnosis. CBMFS are often associated with a
      predisposition to cancer later in life.

PMID- 19167577
TI  - Disorders of the fetomaternal unit: hematologic manifestations in the fetus and
      neonate.
AB  - Histoarchitectural characteristics of the human placenta place the fetus at a
      high risk of growth restriction, abnormal fetomaternal cell traffic, and vertical
      transmission of pathogens. These abnormalities of the fetomaternal unit are
      frequently associated with hematological abnormalities in the fetus/neonate and
      may be the first, most common, or the only clinical manifestations of these
      conditions. This article reviews the pathophysiology and characteristic
      hematological manifestations of these conditions in the fetus and the neonate.

PMID- 19167579
TI  - Current controversies in the management of the anemia of prematurity.
AB  - Preterm infants, especially those with extremely low birth weight (ELBW) are
      exposed to frequent blood draws as part of their care in the neonatal intensive
      care unit. ELBW infants develop the anemia of prematurity (AOP), a hypo
      proliferative anemia marked by inadequate production of erythropoietin (Epo).
      Treatment of AOP includes red blood cell transfusions, which are given to preterm
      infants based on indications and guidelines (hematocrit/hemoglobin levels,
      ventilation and oxygen need, apneas and bradycardias, poor weight gain) that are
      relatively non-specific. In this article we review recent studies evaluating
      transfusion guidelines, discuss ways to decrease phlebotomy losses and examine
      the use of red cell growth factors such as Epo in preventing and treating anemia
      in preterm infants.

PMID- 19167580
TI  - Current approaches to the evaluation and management of the fetus and neonate with
      immune thrombocytopenia.
AB  - Fetal and neonatal alloimmune thrombocytopenia is not a well-known disease,
      except among specialists in maternal-fetal medicine, neonatologists, and certain
      pediatricians (ie, hematologists). However, this is by far the most common cause
      of early severe thrombocytopenia in neonates and of intracranial hemorrhage in
      term neonates. In addition, if a newborn is affected with alloimmune
      thrombocytopenia, the next child in the family will likely be more severely
      affected. Thus, the accurate diagnosis and appropriate management of this
      disorder are of extreme importance in perinatal medicine and will constitute the
      focus of this review.

PMID- 19167582
TI  - The evaluation and management of neonatal coagulation disorders.
AB  - Neonatal hemostatic abnormalities can present diagnostic and therapeutic
      challenges to the physician. Developmental deficiencies and/or increases of
      certain coagulation proteins, coupled with acquired or genetic risk factors, can
      result in a hemorrhagic or thromboembolic emergency. The timely diagnosis of a
      congenital hemorrhagic or thrombotic disorder can avoid significant long-term
      sequelae. However, due to the lack of randomized clinical trials addressing the
      management of neonatal coagulation disorders, treatment strategies are usually
      empiric and not evidence-based. In this chapter, we will review the neonatal
      hemostatic system and will discuss the most common types of hemorrhagic and
      thrombotic disorders. Congenital and acquired risk factors for hemorrhagic and
      thromboembolic disorders will be presented, as well as current treatment options.
      Finally, suggested evaluations for neonates with either hemorrhagic or
      thromboembolic problems will be reviewed.

PMID- 19167581
TI  - New insights into the mechanisms of nonimmune thrombocytopenia in neonates.
AB  - Thrombocytopenia affects up to 35% of all patients admitted to the neonatal
      intensive care unit. The causes of thrombocytopenia in neonates are very diverse
      and include immune and nonimmune disorders. Most cases of thrombocytopenia
      encountered in the neonatal intensive care unit are nonimmune, and these will
      constitute the focus of this review. Specifically, we first discuss the
      biological differences between neonatal and adult megakaryocytopoiesis, which
      contribute to explain the vulnerability of neonates to develop thrombocytopenia.
      Next, we review new diagnostic tools that have allowed for a better evaluation of
      platelet production in neonates, without having to obtain a bone marrow sample.
      Finally, we summarize our current understanding of the mechanisms underlying the
      thrombocytopenia in several common neonatal conditions, such as chronic
      intrauterine hypoxia, sepsis and necrotizing enterocolitis, and viral infections.
      A better understanding of the mechanisms underlying these varieties of
      thrombocytopenia is critical to develop disease-specific treatment protocols and
      to begin to entertain the possibility of using novel thrombopoietic growth
      factors to treat selected neonates with severe thrombocytopenia.

PMID- 19167583
TI  - Platelets, frozen plasma, and cryoprecipitate: what is the clinical evidence for
      their use in the neonatal intensive care unit?
AB  - Transfusion of blood components such as platelets, frozen plasma, and
      cryoprecipitate is a common practice in the neonatal intensive care unit.
      Although it is intuitive that these components would be transfused in the context
      of bleeding, their use in neonatology has often been on a prophylactic basis. Due
      to a lack of consensus guidelines regarding indications for transfusion, however,
      the neonatologist is left to his/her opinion as to when to transfuse. This
      article seeks to review the available evidence regarding the use of platelets,
      frozen plasma, and cryoprecipitate in neonates, as well as the risks associated
      with the administration of these products.

PMID- 19167585
TI  - Intuitiveness, instruction time, and patient acceptance of a prefilled insulin
      delivery device and a reusable insulin delivery device in a randomized, open
      label, crossover handling study in patients with type 2 diabetes.
AB  - BACKGROUND: Because the use of insulin therapy can place a substantial burden on
      patients with diabetes, insulin administration should be as simple as possible.
      OBJECTIVES: The primary aim of this trial was to compare the use of 2 insulin
      delivery devices-one prefilled (NovoMix 30 FlexPen [FP]; Novo Nordisk,
      Copenhagen, Denmark) and the other reusable (HumaPen Luxura [HL]; Eli Lilly and
      Company, Indianapolis, Indiana)-in patients with type 2 diabetes in terms of
      intuitiveness and training time. A secondary aim was to evaluate the ease of use
      and overall acceptance of the 2 devices. METHODS: This was a randomized, open
      label, comparative, crossover handling study in adult patients with type 2
      diabetes who had been treated with oral antidiabetic drugs for >or=2 years and
      had no previous experience with insulin injection devices. Patients were randomly
      allocated to the intuitiveness group (no instruction in the use of the devices
      provided) or the instruction group (instruction provided). The time taken to
      deliver an injection into a cushion was measured for each device in both groups.
      Patients answered questionnaires concerning the intuitiveness and ease of use of
      the 2 devices, their trust and confidence in the devices to deliver the insulin
      dose, and their overall pen preference. RESULTS: Sixty-one patients were enrolled
      in the study (70.5% male; mean [SD] age, 61.80 [7.60] years), 30 in the
      intuitiveness group and 31 in the instruction group. When all handling steps for
      the HL device were included, the mean (SD) injection time was significantly
      shorter for the FP device compared with the HL device in the intuitiveness group
      (1.21 [1.04] vs 1.74 [0.79] minutes, respectively; P = 0.035). The outcome was
      similar in the instruction group (0.71 [0.29] vs 1.09 [0.49] minutes; P < 0.001).
      When the time for cartridge insertion in the HL device was excluded, there was no
      significant difference in injection time for the respective devices in either
      group (intuitiveness group: 1.21 [1.04] and 1.07 [0.91] minutes; instruction
      group: 0.63 [0.35] and 0.71 [0.29] minutes). Twenty-two patients preferred the FP
      device in terms of ease of learning, compared with 8 patients preferring the HL
      device (P = 0.007). CONCLUSIONS: In this study, when all handling steps were
      included, the FP device was associated with significantly greater intuitiveness
      and a shorter injection time compared with the HL device. Further research is
      needed to determine whether these differences between devices are clinically
      meaningful.

PMID- 19167586
TI  - Relative bioavailability of tizanidine hydrochloride capsule formulation compared
      with capsule contents administered in applesauce: a single-dose, open-label,
      randomized, two-way, crossover study in fasted healthy adult subjects.
AB  - BACKGROUND: The alpha2-adrenergic agonist tizanidine has been reported to have a
      narrow therapeutic index. A multiparticulate capsule formulation of tizanidine
      has been developed in an attempt to improve patient tolerability. OBJECTIVE: This
      study assessed bioequivalence between a single, intact, 6-mg capsule of
      tizanidine and the capsule contents sprinkled in applesauce in fasted healthy
      subjects. METHODS: Healthy male and female subjects aged 18 to 45 years completed
      2 treatment periods: one with a tizanidine 6-mg capsule administered intact and
      the other with capsule contents sprinkled in applesauce. The 2 treatment periods
      had a 6-day washout period between administrations. Plasma tizanidine
      concentrations were determined for blood samples collected over 24 hours after
      administration. All treatment-emergent adverse events were recorded and graded by
      intensity and relationship to the study drug (not, improbable, possible,
      probable, definite) by the attending physician based on his or her clinical
      impression. RESULTS: A total of 19 men and 9 women (mean age, 26 years) completed
      the trial. Geometric mean natural logarithm-transformed AUC values (AUC(0
      infinity) [AUC to infinity] and AUC(0-t) [AUC to the last measurable time point])
      and C(max) ratios were significantly (P <or= 0.035) increased to 1.14 (90% CI,
      105.47%-127.01%), 1.16 (90% CI, 106.80%-130.53%), and 1.17 (90% CI, 103.95%
      133.66%), respectively, when the contents were sprinkled, with 90% CIs laying
      outside the 0.80 to 1.25 ratio established by regulatory authorities for
      bioequivalence. A total of 31 adverse events were reported by 17 of the 28
      subjects (61%), including 15 subjects (54%) with the intact capsule reporting 18
      events and 11 subjects (39%) with the sprinkled contents reporting 13 events. No
      serious adverse events or deaths were reported, and no subjects were discontinued
      due to adverse events. CONCLUSIONS: The contents of the tizanidine capsule
      sprinkled in applesauce were not bioequivalent to the intact 6-mg capsule in
      these fasted healthy volunteers. Therefore, if switching from the intact capsule
      to the capsule contents mixed in applesauce, monitoring for adverse events is
      recommended; in this situation, dose adjustment could be necessary.

PMID- 19167587
TI  - Bioequivalence and comparison of pharmacokinetic properties of 4-mg tablet
      formulations of rosiglitazone hydrochloride and rosiglitazone maleate: a single
      dose, randomized, open-label, two-period crossover study in healthy adult male
      Chinese volunteers.
AB  - BACKGROUND: Rosiglitazone is an insulin-sensitizing oral thiazolidinedione used
      for treating patients with type 2 diabetes mellitus. There are 9 oral generic and
      branded formulations of rosiglitazone available in the People's Republic of China
      (PRC); however, a literature search did not identify any published data
      concerning the bioavailability of these formulations in the Chinese population.
      OBJECTIVES: The aims of this study were to compare the pharmacokinetic properties
      and determine the bioequivalence of 2 formulations of rosiglitazone 4-mg tablets
      rosiglitazone hydrochloride (test) and rosiglitazone maleate (reference)-in
      healthy adult male Chinese volunteers. METHODS: This single-dose, randomized,
      open-label, 2-period crossover study was conducted at Zhejiang Provincial
      People's Hospital, Hangzhou, PRC. Healthy adult male Chinese volunteers were
      randomly assigned to receive a single 4-mg dose of the test or reference
      formulation, followed by a 7-day washout period and administration of the
      alternate formulation. The study drugs were administered after a >or=12-hour
      (overnight) fast. Plasma was analyzed for rosiglitazone concentration using a
      validated high-performance liquid chromatography method. For analysis of
      pharmacokinetic properties, including C(max), AUC(0-t), and AUC(0-infinity),
      blood samples were drawn before (0 hour; baseline) and at 10, 20, 30, 45, 60, 75,
      and 90 minutes and 2, 4, 6, 8, 12, and 24 hours after administration. The
      formulations were to be considered bioequivalent if the logarithm-normal (ln)
      transformed ratios of C(max) and AUC were within the predetermined range of 80%
      to 125%, as established by the US Food and Drug Administration. Tolerability was
      assessed using physical examination, including monitoring of vital signs,
      laboratory testing (hematology, blood biochemistry, hepatic function, renal
      function, and urinalysis), and questioning subjects about adverse events (AEs).
      RESULTS: Twenty subjects were enrolled and completed the study (mean [SD] age,
      21.1 [1.4] years; weight, 62.6 [4.6] kg; height, 171 [5] cm; and body mass index,
      21.4 [1.3] kg/m(2)). No period or sequence effects were detected. The 90% CIs for
      the ln-transformed ratios of C(max), AUC(0-24), and AUC(0-infinity) were 96.79 to
      109.73, 92.14 to 102.93, and 91.64 to 102.60, respectively (all, P < 0.001),
      meeting the predetermined criterion for bioequivalence. No AEs were reported in
      this study. CONCLUSIONS: In this small study in these healthy adult male Chinese
      volunteers, a single 4-mg dose of rosiglitazone hydrochloride appeared to be
      bioequivalent to rosiglitazone maleate, according to the regulatory definition,
      based on the rate and extent of absorption. Both formulations were well
      tolerated.

PMID- 19167588
TI  - Tolerability and effects on lipids of ezetimibe coadministered with pravastatin
      or simvastatin for twelve months: results from two open-label extension studies
      in hypercholesterolemic patients.
AB  - OBJECTIVE: The aim of these studies was to assess the long-term tolerability and
      effects on lipids of ezetimibe coadministered with pravastatin or simvastatin
      during treatment of hypercholesterolemic patients. METHODS: Two separate 12
      month, open-label extension studies enrolled patients who had successfully
      completed one of three 12-week, double-blind, placebo-controlled trials of
      ezetimibe coadministered with pravastatin, lovastatin, or simvastatin. In the
      extensions, the initial dose of each drug administered was 10 mg/d, with the
      option to up-titrate the statins if low-density lipoprotein cholesterol (LDL-C)
      goals were not met. Tolerability was assessed using monitoring of clinical and
      laboratory adverse events (AEs). Changes from baseline in LDL-C, total
      cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were
      calculated. RESULTS: Overall, 436 patients received ezetimibe + pravastatin 10 to
      40 mg/d, including patients from the parent studies who received coadministration
      treatment but did not continue in the extension studies; 359 patients received
      ezetimibe + simvastatin 10 to 80 mg/d in the extension study. The majority of
      patients in both studies were white (ezetimibe + pravastatin, 374 [86%];
      ezetimibe + simvastatin, 314 [87%]) and female (ezetimibe + pravastatin, 246
      [56%]; ezetimibe + simvastatin, 210 [58%]). The mean ages were 55.7 and 57.7
      years and the mean body mass indexes were 29.4 and 28.8 kg/m2 in the ezetimibe +
      pravastatin and ezetimibe + simvastatin studies, respectively. The most commonly
      reported AEs with ezetimibe + pravastatin were upper respiratory tract infection
      (78 [18%]), headache (47 [11%]), musculoskeletal pain (45 [10%]), arthralgia (43
      [10%]), and sinusitis (42 [10%]); with ezetimibe + simvastatin, they were upper
      respiratory tract infection (67 [19%]), arthralgia (39 [11%]), and
      musculoskeletal pain (37 [10%]). AEs considered treatment related were reported
      in 98 (22%) and 80 (22%) patients in the ezetimibe + pravastatin and ezetimibe +
      simvastatin studies, respectively. Serious AEs were reported in 29 patients (7%)
      who received ezetimibe + pravastatin and 36 patients (10%) who received ezetimibe
      + simvastatin; <1% were considered treatment related in either study. Forty-one
      (9%) and 29 patients (8%), respectively, were withdrawn due to AEs. One death
      occurred due to cardiopulmonary arrest in the ezetimibe + simvastatin study and
      was not considered treatment related. Percentage changes from baseline in LDL-C
      were -36.5% and -40.4% in patients who received ezetimibe + pravastatin and
      ezetimibe + simvastatin. CONCLUSION: In these 12-month, open-label extension
      studies in these patients with hypercholesterolemia, ezetimibe + pravastatin or
      simvastatin was generally well tolerated. Both treatments were associated with
      maintaining improvements in lipid parameters throughout the studies in these
      patients.

PMID- 19167590
TI  - Effects of short-term and long-term danazol treatment on lipoproteins,
      coagulation, and progression of atherosclerosis: two clinical trials in healthy
      volunteers and patients with hereditary angioedema.
AB  - BACKGROUND: Danazol is a synthetic androgen derivative frequently used as
      prophylaxis in patients with hereditary angioedema (HAE) due to complement-1
      esterase inhibitor deficiency. However, danazol has been reported to decrease
      high-density lipoprotein cholesterol (HDL-C) levels and to adversely affect
      coagulation parameters, which are considered to be proatherothrombotic.
      OBJECTIVE: The short- and long-term effects of danazol were evaluated on
      proatherogenic intermediate end points in healthy volunteers and patients with
      HAE. METHODS: Short-term effects were evaluated in healthy men randomly assigned
      to 200 mg/d of danazol or placebo for 4 weeks in a crossover trial with no
      washout period. Long-term effects of danazol on lipoproteins, coagulation, and
      carotid intima-media thickness (CIMT) were evaluated in a cross-sectional study
      in which patients with HAE treated with danazol, a mean dose of 170 mg/d for
      >or=2 years, were compared with healthy controls matched for age, sex, and body
      mass index (BMI). Drug tolerability was assessed by questionnaires and adherence
      was measured by pill count when drug bottles were returned after every study
      visit. RESULTS: Patients in the short-term study were 15 men with a mean (SD) age
      of 32.6 (6.9) years and BMI of 24.3 (4.1) kg/m(2). In the long-term study,
      patients with HAE were 10 women and 7 men with a mean (SD) age of 41.1 (12.9)
      years and BMI of 25.4 (2.6) kg/m(2); the 17 matched controls had a mean (SD) age
      of 39.8 (11.8) years and BMI of 25.4 (2.6) kg/m(2). Short-term danazol treatment
      was associated with a decrease from baseline in apolipoprotein A-I of 21% and in
      HDL-C of 23%. Flow-mediated dilation and coagulation parameters were unaffected
      after 4 weeks. Longterm danazol treatment did not adversely affect HDL-C
      concentration (1.1 [0.5] vs baseline, 1.2 [0.5] pmol/L), HDL-related transfer
      proteins such as paraoxonase-1 activity (92 [62] vs 80 [40] U/mM), cholesteryl
      ester transfer protein mass (1.5 [0.4] vs 2.2 [0.6] microg/mL), lecithin
      cholesterol acyltransferase activity (21.2 [4.5] vs 32.1 [7.2] nmol CE . mL(-1) .
      h(-1)), plasma phospholipid transfer protein activity (15.4 [1.5] vs 14.9 [1.2]
      AU), and apolipoproteins between patients with HAE and controls. The mean (SD)
      CIMT was similar between patients with HAE and controls (0.62 [0.09] vs 0.59
      [0.08] mm; P = NS). However, HAE patients using danazol had increased coagulation
      activation when compared with controls (prothrombin fragments, 286 [119] vs 164
      [57] pmol/L, P = 0.002; thrombinantithrombin complex, 3.9 [1.4] vs 2.6 [1.1]
      microg/L, P = 0.01). CONCLUSIONS: Short-term danazol treatment in healthy
      volunteers was associated with a reduction in HDL-C levels without a significant
      effect on endothelial function or coagulation parameters. In contrast, patients
      with HAE treated for >2 years with danazol had increased activation of
      coagulation, but there were no significant differences in HDL-C or CIMT compared
      with matched healthy controls.

PMID- 19167589
TI  - Comparative effects of 10-mg versus 80-mg Atorvastatin on high-sensitivity C
      reactive protein in patients with stable coronary artery disease: results of the
      CAP (Comparative Atorvastatin Pleiotropic effects) study.
AB  - BACKGROUND: The major beneficial effect of statins- reducing the risk for
      coronary events-has primarily been ascribed to reductions in low-density
      lipoprotein cholesterol (LDL-C) but may in part be related to a direct
      antiinflammatory action (ie, decreased high-sensitivity C-reactive protein [hs
      CRP] concentration). OBJECTIVES: The objectives of this CAP (Comparative
      Atorvastatin Pleiotropic Effects) study were to compare the effects of low-
      versus high-dose atorvastatin on hs-CRP concentrations and to determine the
      relationship between changes in LDL-C and hs-CRP concentrations in patients with
      coronary artery disease (CAD), low-grade inflammation, and normal lipoprotein
      concentrations. METHODS: This multicenter, prospective, randomized, double-blind,
      double-dummy study was conducted at 65 centers across Canada and Europe. Patients
      with documented CAD, low-grade inflammation (hs-CRP concentration, 1.5-15.0
      mg/L), and a normal-range lipid profile (LDL-C concentration, 1.29-3.87 mmol/L
      [50-150 mg/dL]; triglyceride [TG] concentration, <4.56 mmol/L [<400 mg/dL]) were
      randomly assigned to receive 26-week double-blind treatment with atorvastatin 10
      or 80 mg QD. Investigators were to aim for the National Cholesterol Education
      Program Adult Treatment Panel III (NCEP ATP III) LDL-C target of <2.59 mmol/L
      (<100 mg/dL). The primary end point was the percentage change from baseline in hs
      CRP, as measured at baseline and weeks 5, 13, and 26 using high-sensitivity,
      latex microparticle-enhanced immunoturbidimetric assay. Changes from baseline in
      LDL-C, as measured directly in serum at the same time points, were also
      calculated. The secondary efficacy variables included the percentage changes from
      baseline in lipid parameters (LDL-C, high-density lipoprotein cholesterol [HDL
      C], total cholesterol [TC], TG, apolipoprotein B, non-HDL-C, and TC:HDL-C ratio)
      at 5, 13, and 26 weeks of treatment. Tolerability was assessed using physical
      examination, including vital sign measurement, and laboratory analyses. RESULTS:
      A total of 339 patients were enrolled (283 men, 56 women; mean age, 62.5 years;
      weight, 81.3 kg; 10-mg/d group, 170 patients; 80-mg/d group, 169). No significant
      differences in baseline demographic or clinical data were found between the 2
      treatment arms. In the 10-mg group, hs-CRP was decreased by 25.0% at 5 weeks and
      remained stable thereafter (%Delta at week 26, -24.3%; P < 0.01). In the 80-mg
      group, hs-CRP was decreased by 36.4% at 5 weeks and continued to be decreased
      over the study period (%Delta, -57.1% at week 26; P < 0.001 vs baseline). At 5
      weeks, LDL-C was decreased by 35.9% in the 10-mg group and by 52.7% in the 80-mg
      group (P < 0.001 between groups) and remained stable thereafter (%Delta at week
      26, -34.8% and -51.3%, respectively; P < 0.001 between groups). The NCEP ATP III
      LDL-C target of <2.59 mmol/L (<100 mg/dL) was reached in 77.1% of patients
      treated with atorvastatin 10 mg and 92.3% of those treated with 80 mg (P <
      0.001). Dual targets of hs-CRP <2 mg/L and LDL-C <1.81 mmol/L (<70 mg/dL) were
      reached in a significantly greater proportion of patients in the 80-mg group
      compared with the 10-mg group (55.6% vs 13.5%; P < 0.001). The decrease in hs-CRP
      was largely independent of baseline LDL-C and change in LDL-C. Two serious
      adverse events were reported by the investigator as treatment related: acute
      hepatitis in the 10-mg group and intrahepatic cholestasis in the 80-mg group, in
      2 patients with multiple comorbidities. Two deaths occurred during the study,
      both in the atorvastatin 80-mg group (1, myocardial infarction; 1, sudden death),
      neither of which was deemed treatment related by the investigator. CONCLUSIONS:
      In these patients with documented CAD, evidence of low-grade inflammation, and
      normal range lipid profiles, the effects of atorvastatin on changes in hs-CRP
      were dose dependent, with the high dose (80 mg) being associated with
      significantly greater reductions in hs-CRP concentrations. Both doses were
      associated with a significant and progressive decline in hs-CRP largely
      independent of changes in LDL-C, HDL-C, and TG. Clinical Trials Identification
      Number: NCT00163202.

PMID- 19167591
TI  - A US multicenter, retrospective, observational study of erythropoiesis
      stimulating agent utilization in anemic, critically ill patients admitted to the
      intensive care unit.
AB  - BACKGROUND: Anemia is a common comorbid condition among patients admitted to the
      intensive care unit (ICU). Darbepoietin alfa and epoetin alfa are erythropoiesis
      stimulating agents (ESAs) used to manage anemia in the ICU, although neither drug
      has an indication in critically ill patients. OBJECTIVE: This study describes ESA
      practice patterns in anemic, critically ill patients admitted to the ICU.
      METHODS: A total of 19 hospitals participated in this US multicenter,
      retrospective, observational study of adult patients not receiving chronic
      hemodialysis who were admitted to the ICU for >or=24 hours between February 2005
      and September 2005 and who received >or=1 dose of darbepoietin alfa or epoetin
      alfa. Data on ESA doses, dosing frequencies, hemoglobin levels, and red blood
      cell (RBC) transfusions were abstracted from electronic medical records. RESULTS:
      A total of 438 patients were included in the analysis, of whom 201 (46%) were
      treated with darbepoietin alfa and 237 (54%) were treated with epoetin alfa. In
      the respective groups, similar proportions were male (121/201 [60%] and 126/237
      [53%]) and white (146/195 [75%] and 140/184 [76%]); age was also similar (mean
      [SD], 62 [19] and 60 [18] years). The mean (SD) dose during the first week of ICU
      stay was 96.5 (40.5) microg with darbepoietin alfa and 33,439 (23,508) U with
      epoetin alfa. The most commonly prescribed dosing frequency with darbepoietin
      alfa was once weekly (88.1% of all prescribed doses), with a mean (SD) number of
      injections of 1.8 (1.75). With epoetin alfa, the most common dosing frequencies
      were 3 times weekly (35.9%), 1-time dosing (28.5%), and once weekly (24.0%), with
      a mean (SD) number of injections of 2.9 (4.2). In both groups, the duration of
      therapy was <or=1 week in ~50% of patients, and the mean change in hemoglobin
      concentration was 0.8 g/dL. Overall, 47% (darbepoietin alfa) and 44% (epoetin
      alfa) of patients were RBC transfusion independent (ie, did not require a
      transfusion during their ICU or hospital stay) after receiving the first ESA
      dose. CONCLUSION: Based on these results, it is apparent that the practice
      patterns associated with ESA treatment of critically ill patients admitted to the
      ICU between February 2005 and September 2005 were highly variable.

PMID- 19167592
TI  - Pharmacokinetic/pharmacodynamic modeling to predict in vivo effectiveness of
      various dosing regimens of piperacillin/tazobactam and piperacillin monotherapy
      against gram-negative pulmonary isolates from patients managed in intensive care
      units in 2002.
AB  - OBJECTIVE: This study compared the pharmacokinetic/pharmacodynamic (PK/PD)
      properties of piperacillin/tazobactam (PTZ) combination treatment with those of
      piperacillin (PIP) monotherapy against clinical gram-negative pulmonary isolates
      from US patients treated in intensive care units. METHODS: Computer modeling was
      used to integrate national in vitro microbiologic data from 2002 with
      pharmacokinetic data from published studies in healthy volunteers. PTZ (3.375 g
      q4h, 3.375 g q6h, 4.5 g q6h, and 4.5 g q8h) and PIP (3 g q4h, 3 g q6h, 4 g q6h,
      and 4 g q8h) were modeled using Monte Carlo simulations. The cumulative fraction
      of response (CFR) was determined for percentage of time that the free serum
      concentration remained above the MIC of >or=30% (bacteriostatic) and >or=50%
      (bactericidal). Because simulated comparisons with an artificially derived sample
      size were used, statistical methods were not applied. RESULTS: Overall, 2584 gram
      negative pulmonary isolates were evaluated, including Enterobacteriaceae (n =
      1430), Pseudomonas aeruginosa (n = 799), Acinetobacter baumannii (n = 179), and
      "other" (n = 176). The percents susceptible with PTZ and PIP were as follows:
      Enterobacteriaceae, 86% and 66%, respectively; P aeruginosa, 89% and 84%; and A
      baumannii, 47% and 34%. CFR rates with PTZ were numerically higher than those
      with PIP against Enterobacteriaceae (ranges, 86%-89% and 66%-73%, respectively)
      and A baumannii (47%-53% and 33%-42%), but not against P aeruginosa (79%-84% and
      75%-81%). CONCLUSION: Results from PK/PD models with Monte Carlo simulation
      suggested that susceptibility differences among these selected gram-negative
      isolates collected in 2002 may be of sufficient magnitude to result in notable
      PK/PD differences between PTZ and PIP.

PMID- 19167593
TI  - Pharmacokinetics of 8-hour intravenous infusion of NXY-059: a phase I,
      randomized, double-blind (within dose panels), placebo-controlled study in
      healthy Chinese volunteers.
AB  - BACKGROUND: NXY-059 is a free radical-trapping neuroprotectant that has been
      reported to reduce infarct size and preserve brain function in experimental
      models of acute ischemic stroke. NXY-059 administered as an 8- or 72-hour IV
      infusion has been reported to be well tolerated in healthy young (age, 20-45
      years) and older (55-75 years) white volunteers. NXY-059 is no longer in
      development following a lack of efficacy found in a Phase III trial in patients
      with acute ischemic stroke. OBJECTIVES: The primary objectives of this study were
      to determine the pharmacokinetic (PK) properties of an 8-hour IV infusion of NXY
      059 in healthy Chinese volunteers and to compare those data with those previously
      reported in the white population, therefore exploring any differences in PK
      properties between the 2 ethnic groups. Secondary objectives were to evaluate PK
      linearity and tolerability. METHODS: This Phase I, randomized, double-blind
      (within dose panels), placebo-controlled study was conducted at Peking Union
      Medical College Hospital, Beijing, China. Healthy male and female Chinese
      volunteers aged 20 to 45 years were recruited. NXY-059 was administered as a
      continuous 8-hour IV infusion, starting with a 1-hour loading dose (dosing rate,
      3 x maintenance infusion rate) followed by a 7-hour maintenance dose infusion.
      Subjects were randomly assigned, in a 3:1 ratio, to receive doses calculated
      (based on creatinine clearance in individual subjects) to achieve 1 of 3
      concentration targets, or inactive vehicle (sodium chloride; placebo). The target
      unbound plasma NXY-059 concentrations during constant rate infusion (steady
      state) (Cu(ss)) in the 3 dose panels were 100,200, and 300 micromol/L. An
      explorative bridging analysis was used to compare PK data from this study with
      those previously reported in the white population. Linearity of NXY-059 PK
      properties was assessed. Tolerability was assessed using adverse events
      (spontaneous reporting, study staff observation, and open questioning), physical
      examination, including vital sign measurement; and electrocardiography and
      laboratory analysis. RESULTS: Thirty-six subjects were randomized (mean age, 32
      years [range, 20-41 years]; mean body mass index, 22.6 kg/m(2) [range, 20-26
      kg/m(2)]). The target exposures of NXY-059 were achieved (mean [SD] Cu(ss)
      values, 98.3 [8.9], 202.1 [18.3], and 287.9 [25.4] micromol/L, respectively).
      Steady-state concentrations appeared to have been reached after 4 hours. From the
      bridging analysis, comparison of PK properties in the 27 Chinese volunteers
      versus those in 28 white volunteers found similar total plasma clearance of NXY
      059 (estimated Chinese:white clearance ratio, 1.077 [95% CI, 1.009-1.150]). There
      were no apparent differences in other PK parameters between the 2 ethnic groups.
      The PK properties of NXY-059 in Chinese volunteers were suggestive of linearity.
      A total of 7 adverse events were reported, all of mild intensity, in the NXY-059
      and placebo groups (thirst and polyuria [each in 2 subjects who received NXY-059
      and 1 subject who received placebo]; urinary tract infection [1 subject who
      received NXY-059]). CONCLUSIONS: The results from the present study suggest that
      the PK properties of NXY-059 were similar in the Chinese and historical white
      healthy volunteer populations.

PMID- 19167594
TI  - Antihypertensive efficacy and tolerability of irbesartan/hydrochlorothiazide in
      hypertensive patients stratified by body mass index and type 2 diabetes mellitus
      status: a post hoc subgroup analysis of the Irbesartan/HCTZ Blood Pressure
      Reductions in Diverse Patient Populations trial.
AB  - OBJECTIVE: This was a post hoc subgroup analysis of efficacy and tolerability
      data from the Irbesartan/HCTZ Blood Pressure Reductions in Diverse Patient
      Populations (INCLUSIVE) trial stratified by baseline body mass index (BMI). The
      BMI subgroup data were also analyzed according to the presence or absence of type
      2 diabetes mellitus (T2DM) at baseline. METHODS: The 18-week, prospective,
      multicenter, open-label, single-arm INCLUSIVE trial evaluated the efficacy and
      tolerability of a fixed-dose combination of irbesartan/hydrochlorothiazide (HCTZ)
      in adult hypertensive patients with systolic blood pressure (SBP) that was
      uncontrolled after >or=4 weeks of monotherapy. Patients received placebo for 4 to
      5 weeks, HCTZ 12.5 mg for 2 weeks, irbesartan/HCTZ 150/12.5 mg for 8 weeks, and
      irbesartan/HCTZ 300/25 mg for 8 weeks. Patients were stratified into BMI
      subgroups based on values at screening. Normal weight was defined as a BMI
      <or=24.9 kg/m(2), overweight as a BMI of 25 to 29.9 kg/m(2), and obesity as a BMI
      >or=30 kg/m(2). The primary efficacy end point was the mean change in SBP from
      baseline (end of the placebo phase) to week 18 in the overall intent-to-treat
      (ITT) population. Secondary efficacy end points were the mean changes in SBP and
      diastolic blood pressure (DBP) from baseline to week 18 in each BMI subgroup, the
      proportions of patients in each BMI subgroup achieving their SBP target (<140 mm
      Hg [<130 mm Hg for patients with T2DM]) and DBP target (<90 mm Hg [<80 mm Hg for
      patients with T2DM]), and the mean SBP and DBP responses at the end of each
      treatment period. RESULTS: The ITT population included 736 patients, of whom 99
      (13.5%) were normal weight, 243 (33.0%) were overweight, and 394 (53.5%) were
      obese. Mean baseline SBP and DBP values were similar across BMI subgroups. Obese
      patients were generally younger than normal-weight and overweight patients, and
      numerically more obese patients had T2DM and metabolic syndrome. The mean
      reductions in SBP and DBP at week 18 were statistically significant in all
      subgroups (all, P < 0.001); SBP and DBP goals were achieved by a respective 83.8%
      and 93.9% of normal-weight patients, 75.3% and 87.7% of overweight patients, and
      76.9% and 77.2% of obese patients. Rates of SBP/DBP control to <140/90 mm Hg in
      normal weight, overweight, and obese patients without T2DM were 88.2%, 79.8%, and
      80.9%, respectively; the corresponding rates of control to <130/80 mm Hg in
      patients with T2DM were 50.0%, 41.5%, and 38.5%. CONCLUSION: In this post hoc
      subgroup analysis of the INCLUSIVE trial, irbesartan/HCTZ combination therapy had
      comparable antihypertensive efficacy and tolerability regardless of BMI or
      diabetes status.

PMID- 19167595
TI  - Comparison of the effectiveness and tolerability of lidocaine patch 5% versus
      celecoxib for osteoarthritis-related knee pain: post hoc analysis of a 12 week,
      prospective, randomized, active-controlled, open-label, parallel-group trial in
      adults.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) selective inhibitors and nonselective NSAIDs
      are commonly used to treat osteoarthritis (OA) of the knee. OBJECTIVE: The aim of
      this study was to compare the effectiveness of the lidocaine patch 5% with that
      of celecoxib 200 mg/d in the treatment of OA-related knee pain; however, the
      study was terminated prematurely by the sponsor because of tolerability concerns
      regarding the class of COX-2 selective inhibitors. A post hoc analysis of the
      available data is presented here. METHODS: This multicenter, randomized, open
      label, active-controlled, parallel-group study included patients >or=18 years of
      age with unilateral or bilateral moderate to severe OA of the knee. Patients were
      randomized to receive treatment with either the lidocaine patch 5% or celecoxib
      200 mg/d. The primary efficacy end point was change from baseline to 12 weeks in
      the Western Ontario and McMaster Universities (WOMAC) OA Index pain subscale.
      Secondary end points included additional WOMAC subscales and Brief Pain Inventory
      (BPI) measures. Because this trial was prematurely terminated, a post hoc
      analysis was performed using a random pattern-mixture model of all observed cases
      of the intent-to-treat population. RESULTS: A total of 143 patients were
      randomized to treatment (lidocaine patch 5%, 69 patients; mean [SD] age, 60.2
      [11.4] years; 65.2% female; 66.7% white; weight, 94.1 [23.3] kg) or celecoxib 200
      mg/d (74 patients; age, 58.2 [12.1] years; 63.5% female; 68.9% white; weight,
      94.3 [22.5] kg). Baseline pain WOMAC OA subscale scores (lidocaine patch 5%,
      12.087; celecoxib 200 mg/d, 12.514) and mean rates of change over time (baseline
      to week 2, -1.5916 vs -1.6513 per week; weeks 2-6, -0.0168 vs -0.119 per week;
      weeks 6-12, -0.1818 vs -0.1579 per week) were not significantly different between
      the 2 groups. Improvement in additional WOMAC subscales and in several BPI
      measures were not significantly different between the 2 groups. Treatment-related
      adverse events were reported in 8 patients in each treatment group (11.6% in the
      lidocaine patch 5% group and 10.8% in the celecoxib 200-mg/d group) and were
      considered mild or moderate in severity. CONCLUSION: Statistically significant
      differences in effectiveness and tolerability were not found between these 2
      treatments in these patients with OA knee pain.

PMID- 19167596
TI  - Oral versus injectable antipsychotic treatment in early psychosis: post hoc
      comparison of two studies.
AB  - BACKGROUND: Few studies have compared long-acting injectable second-generation
      antipsychotics with oral antipsychotics. Long-acting injectable antipsychotics
      developed specifically to address the problem of adherence-might have an
      important role to play in treating early psychosis. OBJECTIVE: The effects of
      oral antipsychotics versus risperidone long-acting injection (RLAI) were compared
      between 2 similar studies lasting 2 years each that were conducted at our site in
      South Africa. METHODS: Results of an open-label study in which patients were
      treated with flexible doses of RLAI were compared with the results of a
      randomized controlled trial of flexible doses of oral risperidone or haloperidol.
      Inclusion criteria for both studies were age 16 to 45 years; confirmed diagnosis
      of schizophrenia, schizophreniform disorder, or schizoaffective disorder; <or=2
      hospitalizations for psychosis; and lifetime exposure to <or=12 weeks of
      antipsychotic medication. The dose of RLAI was 25 mg every 2 weeks, which could
      be increased to 50 mg. Doses of oral risperidone or haloperidol began at 1 mg/d
      and were increased if necessary up to a maximum dose of 4 mg/d (8 mg/d in
      exceptional cases). Study assessments included the Positive and Negative Syndrome
      Scale (PANSS), the Extrapyramidal Symptom Rating Scale (ESRS), and body mass
      index (BMI). RESULTS: The RLAI group included 50 patients (32 men and 18 women;
      mean [SD] age, 25.4 [7.4] years; BMI, 20.6 [4.6] kg/m(2)). The oral risperidone
      or haloperidol group included 47 patients (27 men and 20 women; mean [SD] age,
      25.9 [5.8] years; BMI, 20.1 [3.4] kg/m(2)). Compared with patients treated with
      oral risperidone or haloperidol, RLAI-treated patients had significantly fewer
      all-cause discontinuations (26.0% [13/50] vs 70.2% [33/47] at 24 months; P <
      0.005), greater reduction on the PANSS total score (-39.7 vs -25.7; P = 0.009),
      higher remission rate (64.0% [32/50] vs 40.4% [19/47]; P = 0.028), and lower
      relapse rate (9.3% [4/43] vs 42.1% [16/38]; P = 0.001) among the responders.
      Extrapyramidal symptoms were significantly lower in the RLAI group than in
      patients treated with oral risperidone or haloperidol, as measured by the maximum
      change in the mean [SD] ESRS total score (1.40 [2.60] vs 5.61 [5.21] vs 9.04
      [6.21], respectively; P <or= 0.001). The increase in BMI after 6 months was
      significantly greater in the RLAI group than in oral haloperidol-treated patients
      (mean [SD], 3.9 [1.9] vs 2.2 [1.3] kg/m(2); P = 0.001) but not significantly
      different from oral risperidone (3.4 [2.0] kg/m(2); P = NS). Four patients in the
      RLAI group had adverse events that were possibly related to prolactin, compared
      with 1 each in the oral risperidone and haloperidol groups. CONCLUSIONS: The
      findings of this post hoc analysis suggest that there were advantages in terms of
      efficacy, fewer extrapyramidal symptoms, and more weight gain with long-acting
      injectable second-generation antipsychotics as compared with oral antipsychotic
      treatment in early-episode psychosis.

PMID- 19167597
TI  - Models for the prediction of mycophenolic acid area under the curve using a
      limited-sampling strategy and an enzyme multiplied immunoassay technique in
      Chinese patients undergoing liver transplantation.
AB  - BACKGROUND: An enzyme multiplied immunoassay technique (EMIT) provides convenient
      and accurate measurements of mycophenolic acid (MPA) concentrations for
      determination of immunosuppression during treatment with mycophenolate mofetil
      (MMF). No abbreviated model for estimating the full 12-hour MPA AUC using an EMIT
      assay in liver transplant recipients has been described previously. OBJECTIVE:
      This study was conducted to determine the best model for predicting the MPA AUC
      using the EMIT method and a limited-sampling strategy in Chinese patients
      undergoing liver transplantation. METHODS: The study enrolled consecutive liver
      transplant patients who were receiving MMF 1 g BID along with tacrolimus. A
      complete MPA pharmacokinetic profile was obtained for each patient on a single
      day, 7 to 14 days after transplantation. The EMIT method was used to determine
      MPA concentrations before dosing and at 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours
      after dosing on the sampling day. Multiple linear regression analysis was used to
      evaluate potential models for estimating the full 12-hour MPA AUC. The accuracy
      and robustness of the models were evaluated using bootstrap analysis. Prediction
      error and prediction bias were calculated. Agreement between the estimated MPA
      AUC(0-12) and the full 12-hour MPA AUC was investigated using Bland-Altman
      analysis. RESULTS: The study enrolled 48 Chinese liver transplant recipients (45
      male, 3 female) with a mean (SD) age of 50 (12) years, mean weight of 64 (12) kg,
      and mean height of 169 (6) cm. Twenty-four models that included blood sampling at
      1 through 4 time points were developed (r(2) = 0.015-0.950). Four models with the
      highest r(2) values were selected; the lack of significant differences from the
      original dataset on bootstrap analysis indicated acceptable accuracy and
      robustness. The best model for predicting the MPA AUC(0-12) employed
      concentrations at 1, 2, 4, and 8 hours; 40 of 48 (83.3%) MPA AUC(0-12) values
      estimated using this model were within 15% of the full 12-hour MPA AUC. This
      model had a minimal mean prediction error (mean [SD], 0.27% [1.79%]) and mean
      absolute prediction error (8.83% [1.24%]). On Bland-Altman analysis, this model
      also had the best agreement between the estimated MAP AUC(0-12) and the full 12
      hour MPA AUC, with a mean error of 9.02 mg . h/L. CONCLUSIONS: In this small
      group of Chinese liver transplant patients receiving MMF and concomitant
      tacrolimus, models for estimating the MPA AUC(0-12) were developed using the EMIT
      method and a limited-sampling strategy. The best model for prediction of the full
      12-hour MPA AUC was 4.46 + 0.81 . C1 + 1.78 . C(2)+2.51.C(4)+4.94.C8.

PMID- 19167598
TI  - Prolonged intrahepatic cholestasis after exposure to loxoprofen.
AB  - OBJECTIVE: The objective of this report was to describe a case of prolonged
      intrahepatic cholestasis likely associated with the use of loxoprofen, a
      phenylpropionate NSAID. METHODS: A 36-year-old female patient was transferred to
      Gunma University Hospital, Maebashi, Japan, with progressive pruritus and
      jaundice that developed after 5-day treatment with 120 mg/d of loxoprofen
      (maximum recommended dose, 180 mg/d) for menstrual pain. Liver function tests
      found the following concentrations: total bilirubin, 27.5 mg/dL (normal [nl]
      range, 0.3-1.2 mg/dL); aspartate aminotransferase, 151 IU/L (nl, 13-33 IU/L);
      alkaine aminotransferase, 470 IU/L (nl, 8-42 IU/L); alkaline phosphatase, 1082
      IU/L (n1, 115-359 IUAL); and gamma-glutamyl transpeptidase, 795 IU/L (nl, 10-47
      IU/L) indicative of intrahepatic cholestasis. No use of alcohol or other drugs or
      herbal products was reported. The patient had a history of elevated hepatic
      enzymes of unknown origin following the use of mefenamic acid. The patient was
      prescribed ursodeoxycholic acid 3 weeks after the onset of symptoms of
      intrahepatic cholestasis. Thereafter, due to progressive cholestasis, an IV pulse
      of methylprednisolone (1000 mg/d) and the herbal product Inchin-ko-to (TJ-135)
      were administered. Plasma bilirubin adsorption (PA) and plasma exchange (PE) were
      performed. RESULTS: Following treatment with PA and PE for 3 weeks with
      administration of methylprednisolone and Inchin-ko-to, signs and symptoms of
      intrahepatic cholestasis began to resolve (3.5 months after the onset); they were
      completely resolved 8 months after the initial episode. A Naranjo scale score of
      6 suggested that loxoprofen was likely the cause of the prolonged cholestasis in
      this patient. CONCLUSION: Based on the Naranjo score, this case of prolonged
      intrahepatic cholestasis in a young woman was likely associated with loxoprofen
      use.

PMID- 19167599
TI  - Describing response scales in patient-reported outcome measures: terms matter.

PMID- 19167600
TI  - Relationship between compliance and persistence with osteoporosis medications and
      fracture risk in primary health care in France: a retrospective case-control
      analysis.
AB  - BACKGROUND: Nonadherence to treatment is an important determinant of long-term
      outcomes in women with osteoporosis. OBJECTIVES: This study was conducted to
      investigate the association between adherence and osteoporotic fracture risk and
      to identify optimal thresholds for good compliance and persistence. A secondary
      objective was to perform a preliminary evaluation of the cost consequences of
      adherence. METHOD: This was a retrospective case-control analysis. Data were
      derived from the Thales prescription database, which contains information on >1.6
      million patients in the primary health care setting in France. Cases were women
      aged >or=50 years who had an osteoporosis-related fracture in 2006. For each
      case, 5 matched controls were randomly selected. Both compliance and persistence
      aspects of treatment adherence were examined. Compliance was estimated based on
      the medication possession ratio (MPR). Persistence was calculated as the time
      from the initial filling of a prescription for osteoporosis medication until its
      discontinuation. RESULTS: The mean (SD) MPR was lower in cases compared with
      controls (58.8% [34.7%] vs 72.1% [28.8%], respectively; P < 0.001). Cases were
      more likely than controls to discontinue osteoporosis treatment (50.0% vs 25.3%;
      P < 0.001), yielding a significantly lower proportion of patients who were still
      persistent at 1 year (34.1% vs 40.9%; P < 0.001). MPR was the best predictor of
      fracture risk, with an area under the receiver-operating-characteristic curve
      that was higher than that for persistence (0.59 vs 0.55). The optimal MPR
      threshold for predicting fracture risk was >or=68.0%. Compared with less
      compliant women, women who achieved this threshold had a 51% reduction in
      fracture risk. The difference in annual drug expenditure between women achieving
      this threshold and those who did not was approximately euro300. The optimal
      threshold for persistence with therapy was at least 6 months. Attaining this
      threshold was associated with a 28% reduction in fracture risk compared with less
      persistent women. CONCLUSIONS: In this study, better treatment adherence was
      associated with a greater reduction in fracture risk. Compliance appeared to
      predict fracture risk better than did persistence.

PMID- 19167601
TI  - Adherence to guidelines for use of erythropoiesis-stimulating agents in patients
      with chemotherapy-induced anemia: results of a retrospective study of an
      electronic medical-records database in the United States, 2002-2006.
AB  - BACKGROUND: Chemotherapy-induced anemia (CIA) commonly occurs in cancer patients
      receiving conventional myelosuppressive chemotherapy. Two national guidelines
      regarding the use of erythropoiesis-stimulating agents (ESAs) in CIA were
      released in 2002. Because of poorer disease outcomes and increased risk of
      adverse events associated with ESAs in recent studies, the use of ESAs has been
      increasingly restricted in practice guidelines in the years 2007 and 2008.
      OBJECTIVE: The aim of this study was to provide a baseline for adherence to
      national guidelines in the use of ESAs for CIA between 2002 and 2006. METHODS:
      This retrospective study used the Varian Medical Oncology database (Varian
      Medical Systems, Inc., Palo Alto, California) of electronic medical records,
      representing 17 outpatient oncology organizations at 71 clinic locations in the
      United States. Adults diagnosed with any malignant neoplasm who started
      conventional cytotoxic chemotherapy between January 1, 2002, and September 30,
      2006, were included. The proportion of patients receiving an ESA was calculated
      by hemoglobin (Hb) level during each chemotherapy cycle, stratified by line of
      chemotherapy and year. Logistic regression modeling identified predictors of ESA
      use in anemic patients during the first chemotherapy cycle. RESULTS: The records
      of 17,731 cancer patients were evaluated. Median (SD) age was 61 (13) years, and
      58.9% were female. Most patients (84.1%) had a solid tumor. Many patients (41.3%)
      received platinum containing chemotherapy and 74.4% received combination
      chemotherapy. During the first 5 cycles of first-line chemotherapy among patients
      with CIA (Hb <11 g/dL), ESAs were used by 55.8% of patients at cycle 1 and 68.9%
      at cycle 5. ESA use in CIA patients increased across lines of chemotherapy and
      time. Few patients (2.8%) received an ESA at Hb >13 g/dL. The statistically
      significant predictors of ESA use included age >65 years, eastern US residence,
      private health insurance, community-based care, and solid tumors, especially lung
      cancer. CONCLUSION: The patterns we observed were generally consistent with
      prevailing ESA labels and national guidelines during 2002 through 2006. Although
      ESA use in patients with CIA increased over chemotherapy cycles, lines of
      chemotherapy, and time, <70% of CIA episodes were treated with ESAs during the
      initial 5 chemotherapy cycles.

PMID- 19167602
TI  - Cost-effectiveness of ranibizumab compared with photodynamic treatment of
      neovascular age-related macular degeneration.
AB  - OBJECTIVE: This study compared the cost-effectiveness of ranibizumab with that of
      photodynamic therapy (PDT) in the treatment of predominantly classic choroidal
      neovascularization secondary to age-related macular degeneration (AMD) from the
      perspective of a third-party payer in a Spanish setting. METHODS: We constructed
      a Markov model with 5 states defined by visual acuity (VA) in the better-seeing
      eye (Snellen scale), as follows: VA >20/40, <or=20/40 to >20/80, </or20/80 to
      >20/200, <or=20/200 to >20/400, and <or=20/400. A death state was also included.
      We took transition probabilities, number of ranibizumab injections, and number of
      PDT treatments from the ANCHOR (Anti-Vascular Endothelial Growth Factor Antibody
      for the Treatment of Predominantly Classic Choroidal Neovascularization in Age
      Related Macular Degeneration) trial. Utilities were taken from a published study
      of patients' preferences. We used unit costs from our hospital and drug costs
      from a national database. Resource utilization was determined by an
      ophthalmologist according to current clinical practice. We performed univariate,
      threshold, and probabilistic sensitivity analyses. Incremental costs (2007 euro)
      and quality-adjusted life-years (QALYs), both discounted at a 3% annual rate, and
      incremental cost-effectiveness ratios (ICERs; euro/QALY) were determined for the
      2-year and life-expectancy time horizons. RESULTS: Treating patients with varying
      degrees of visual impairment with ranibizumab instead of PDT, with a 2-year time
      horizon, was found to be euro18,328 more costly and to confer 0.140 additional
      QALY (euro131,275/QALY). This ICER was reduced to euro39,398/ QALY for the longer
      life-expectancy time horizon. According to the probabilistic sensitivity
      analysis, PDT is the therapy of choice in all cases below the threshold of
      euro30,000/QALY for the 2-year time horizon. Ranibizumab was the optimal
      intervention in 26% of cases in the longer lifetime horizon. When the initial VA
      was <or=20/400, the ICER increased to euro255,477 over 2 years. When ranibizumab
      was administered on an as-needed basis, as in the PrONTO (Prospective Optical
      coherence tomography imaging of patients with Neovascular AMD Treated with intra
      Ocular ranibizumab) trial, the ICERs were reduced to euro29,566/QALY and
      euro11,469/QALY in the 2-year and life-expectancy horizons, respectively.
      CONCLUSIONS: Based on these results, ranibizumab was not cost-effective when
      administered on a monthly basis. When administered as needed, ranibizumab was
      cost-effective compared with PDT for the treatment of AMD.

PMID- 19167603
TI  - Persistence with migraine prophylactic treatment and acute migraine medication
      utilization in the managed care setting.
AB  - OBJECTIVE: The aim of this study was to describe persistence with migraine
      prophylactic treatment and acute migraine medication utilization in patients
      prescribed migraine prophylaxis. METHODS: For this retrospective cohort study,
      the Health Core Integrated Research Database provided pharmacy/medical claims
      data from 5 commercial health insurance plans (ie, excluding Medicare and
      Medicaid) on adult patients with migraine. Eligible patients had >or=1 pharmacy
      claim for a migraine prophylactic medication between July 1, 2000, and May 31,
      2005, and >or=12 U of any combination of acute treatment (serotonin receptor
      agonist [triptan], ergotamine, or ergotamine combination) dispensed during the
      180-day period preceding a first pharmacy claim for a prophylactic medication
      (index date). The prophylactic medication identified at index date was used for
      categorizing patients into 1 of 4 cohorts: amitriptyline, propranolol/timolol,
      divalproex sodium, or topiramate (reference). Kaplan-Meier curves were used for
      evaluating unadjusted risk for discontinuation over time, and a multivariate Cox
      proportional hazards model was developed to analyze factors associated with
      discontinuation of prophylactic medication. RESULTS: A total of 12,783 patients
      met the inclusion criteria and were included in the analysis (amitriptyline,
      3749; propranolol/timolol, 2718; divalproex sodium, 1644; and topiramate, 4672).
      The mean (SD) ages were not significantly different across cohorts (43.9 [11.3],
      42.0 [11.1], 43.1 [11.3], and 43.9 [10.6] years, respectively). The mean duration
      of treatment was significantly longer (131 [184] days) with topiramate compared
      with amitriptyline (94 [152] days), propranolol/ timolol (119 [180] days), and
      divalproex sodium (109 [158] days) (P < 0.001, P = 0.005, and
      P<0.001,respectively). The risks for discontinuing prophylactic treatment were
      23%, 6%, and 11% higher with amitriptyline, propranolol/timolol, and divalproex
      sodium, respectively, compared with topiramate (P<0.001, P = 0.024, and P
      <0.001). Patients prescribed topiramate had a higher mean consumption rate of
      triptans preindex; postindex, decreases in triptan use were observed in all
      cohorts, although the magnitude of the decrease was greatest in patients
      prescribed topiramate compared with the other cohorts. CONCLUSIONS: In this
      study, prescription of topiramate was associated with greater persistence with
      prophylactic treatment than the other prophylactic drugs. Furthermore, greater
      reductions in acute treatment utilization, particularly triptans, were observed
      among patients prescribed topiramate compared with the other prophylactic
      cohorts.

PMID- 19167604
TI  - Perception of prescription medicine sample packs among Australian professional,
      government, industry, and consumer organizations, based on automated textual
      analysis of one-on-one interviews.
AB  - BACKGROUND: Prescription medicine samples provided by pharmaceutical companies
      are predominantly newer and more expensive products. The range of samples
      provided to practices may not represent the drugs that the doctors desire to have
      available. Few studies have used a qualitative design to explore the reasons
      behind sample use. OBJECTIVE: The aim of this study was to explore the opinions
      of a variety of Australian key informants about prescription medicine samples,
      using a qualitative methodology. METHODS: Twenty-three organizations involved in
      quality use of medicines in Australia were identified, based on the authors'
      previous knowledge. Each organization was invited to nominate 1 or 2
      representatives to participate in semistructured interviews utilizing seeding
      questions. Each interview was recorded and transcribed verbatim. Leximancer v2.25
      text analysis software (Leximancer Pty Ltd., Jindalee, Queensland, Australia) was
      used for textual analysis. The top 10 concepts from each analysis group were
      interrogated back to the original transcript text to determine the main emergent
      opinions. RESULTS: A total of 18 key interviewees representing 16 organizations
      participated. Samples, patient, doctor, and medicines were the major concepts
      among general opinions about samples. The concept drug became more frequent and
      the concept companies appeared when marketing issues were discussed. The
      Australian Pharmaceutical Benefits Scheme and cost were more prevalent in
      discussions about alternative sample distribution models, indicating interviewees
      were cognizant of budgetary implications. Key interviewee opinions added richness
      to the single-word concepts extracted by Leximancer. CONCLUSIONS: Participants
      recognized that prescription medicine samples have an influence on quality use of
      medicines and play a role in the marketing of medicines. They also believed that
      alternative distribution systems for samples could provide benefits. The cost of
      a noncommercial system for distributing samples or starter packs was a concern.
      These data will be used to design further research investigating alternative
      models for distribution of samples.

PMID- 19167605
TI  - Association between manganese superoxide dismutase polymorphism and risk of lung
      cancer.
AB  - Manganese superoxide dismutase (MnSOD) is one of the major enzymes responsible
      for the defense against oxidative damage due to reactive oxygen species (ROS) in
      the mitochondria. C-->T substitution in the MnSOD gene (SOD2) produces an Ala-
      >Val change at amino acid 16, in the mitochondrial targeting sequence of the
      MnSOD precursor. This seems to reduce transport of the enzyme into mitochondria,
      decreasing its defense capacity against oxidative stress. The present case
      control study was conducted to investigate the association of SOD2 genetic
      polymorphism with individual susceptibility to lung cancer. Ala16Val
      polymorphisms were determined using polymerase chain reaction, restriction
      fragment length polymorphism mapping, and agarose gel electrophoresis techniques
      in 100 lung cancer patients and 50 healthy control subjects. The frequency of the
      Val allele (OR=1.297, 95% CI=1.095-1.536) and the Val/Val genotype (OR=7.00, 95%
      CI=2.282-21.476) was significantly higher in lung cancer patients than in control
      subjects. There was a combined effect of Val/Val genotype as a genetic factor
      with smoking as an environment factor (OR=2.24). The increase in risk of lung
      cancer was lesser with this combined effect than with the Val/Val genotype alone.
      Thus, the Val/Val genotype of SOD2 may be associated with lung cancer in a
      Turkish population.

PMID- 19167606
TI  - Simulation-based analyses reveal stable microsatellite sequences in human
      pancreatic cancer.
AB  - Genomic analysis using tissue samples is an essential approach in cancer
      genetics. However, technical and biological limits exist in this approach.
      Microsatellite instability (MSI) is frequently observed in human tumors. MSI
      assays are now prevalent and regarded as commonplace. However, several technical
      problems have been left unsolved in the conventional assay technique. Indeed, the
      reported frequencies of MSI differ widely in each malignancy. An example is
      pancreatic cancer. Using a unique fluorescent technique, we found that MSI is
      extremely infrequent in this malignancy, despite the relatively high frequencies
      in some reports. In a series of simulations, we have demonstrated that the
      extremely low frequency was derived neither from less sensitive assays nor from a
      scarcity of cancer cells in tissue samples. Furthermore, analyzing laser-capture
      microdissection (LCM)-processed cell populations of a microsatellite-unstable
      colorectal cancer cell line, HCT116, we have shown that MSI can be detected only
      when comparing two cell populations that have grown independently to a
      sufficiently large size. When MSI is not detected in analyses using tissue
      samples, LCM is not advisable. We therefore did not extend our study to LCM of
      tissue specimens. We conclude that microsatellite sequence alterations are not
      detectable in human pancreatic cancer.

PMID- 19167607
TI  - An investigation of microRNAs mapping to breast cancer related genomic gain and
      loss regions.
AB  - Various regions of amplification or loss are observed in breast tumors as a
      manifestation of genomic instability. To date, numerous oncogenes or tumor
      suppressors on some of these regions have been characterized. An increasing body
      of evidence suggests that such regions also harbor microRNA genes with crucial
      regulatory roles in cellular processes and disease mechanisms, including cancer.
      Here, we investigated 35 microRNAs localized to common genomic gain and/or loss
      regions in breast cancers. To examine amplification or loss of these microRNAs as
      a result of genomic instability, we performed semiquantitative duplex polymerase
      chain reaction in 20 breast cancer cell lines, 2 immortalized mammary cell lines,
      and 2 normal DNA controls. A comprehensive DNA fold number change data for 35
      microRNA genes on chromosomal gain/loss regions are presented in breast cancer
      cells. A 23% (8/35) of the investigated microRNAs showed significant fold number
      increases (greater than fourfold) compared to GAPDH in one or more of the breast
      cell lines. Although no homozygous deletions were detected, fold number decreases
      indicating potential loss regions were observed for 26% (9/35) of the
      investigated microRNAs. Such fold number changes may point out some of these
      microRNAs as potential targets of the genomic instability regions as oncogene and
      tumor suppressor candidates.

PMID- 19167608
TI  - Marker chromosomes are a significant mechanism of high-level RUNX1 gene
      amplification in hematologic malignancies.
AB  - To understand the cytogenetic mechanisms responsible for multiple RUNX1 gene copy
      numbers in hematologic malignancies, we analyzed the chromosomal and molecular
      cytogenetic findings in bone marrow or peripheral blood samples of individuals
      who were diagnosed with acute myeloid leukemia (AML), myelodysplastic syndrome
      (MDS), or acute lymphoblastic leukemia (ALL). Included in the analysis were 113
      consecutive samples received in our laboratory between January 2005 and June
      2007. Bone marrow and/or peripheral blood samples were characterized using
      conventional G-banding techniques and fluorescent in situ hybridization (FISH)
      techniques with commercially available RUNX1/RUNX1T1 or ETV6/RUNX1 dual-color
      fusion probes. Eighty-one (72%) of the 113 samples showed an abnormal karyotype
      and/or abnormal FISH results. Eight of these had, by interphase FISH,
      RUNX1/RUNX1T1 or RUNX1/ETV6 fusion, and 19 had three or more RUNX1 signals not
      related to fusion with RUNX1T1 or ETV6 gene. Of the 19 cases with multiple RUNX1
      gene signals, 5 had high-level RUNX1 amplification--defined as 5 or more RUNX1
      signals in interphase cells--whereas the remaining 14 had 3-4 RUNX1 signals. Four
      of the five tumors with high-level RUNX1 amplification were myeloid disorders-
      three cases of AML and one case of MDS. The karyotypes of tumors with high-level
      amplification of RUNX1 were significantly characterized by the presence of marker
      chromosomes that harbored extra copies of the RUNX1 gene compared with tumors
      that had three to four RUNX1 gene signals (P=0.026, Fisher's exact test). Our
      findings show that high-level RUNX1 amplification, especially in myeloid
      disorders, often results from marker chromosomes harboring extra copies of the
      RUNX1 gene . This suggests that amplification of RUNX1 in these tumors may be
      secondary to a previous rearrangement of 21q22, which later evolved into a
      complex marker chromosome as part of tumor progression.

PMID- 19167609
TI  - Non-classical karyotypic features in relapsed childhood B-cell precursor acute
      lymphoblastic leukemia.
AB  - Karyotype analysis of acute lymphoblastic leukemia (ALL) at diagnosis has
      provided valuable prognostic markers for treatment stratification. However,
      reports of cytogenetic studies of relapsed ALL samples are limited. We compared
      the karyotypes from 436 nonselected B-cell precursor ALL patients at initial
      diagnosis and of 76 patients at first relapse. We noticed a relative increase of
      karyotypes that did not fall into the classic ALL cytogenetic subgroups (high
      hyperdiploidy, t(12;21), t(9;22), 11q23, t(1;19), <45 chromosomes) in a group of
      29 patients at relapse (38%) compared to 130 patients at presentation (30%). Non
      classical cytogenetic aberrations in these 29 patients were mostly found on
      chromosomes 1, 2, 7, 9, 13, 14, and 17. We also describe six rare reciprocal
      translocations, three of which involved 14q32. The most frequent abnormalities
      were found in 9p (12/29 cases) and were associated with a marked decrease in the
      duration of the second remission, but not of the probability of 10-year event
      free survival after relapse treatment. From 29 patients with non-classical
      cytogenetic aberrations, only 8 (28%) had been stratified to a high risk-arm on
      the first treatment protocol, suggesting that this subgroup might benefit from
      the identification of new prognostic markers in future studies.

PMID- 19167610
TI  - Array comparative genomic hybridization, expression array, and protein analysis
      of critical regions on chromosome arms 1q, 7q, and 8p in adenocarcinomas of the
      gastroesophageal junction.
AB  - Survival rates of adenocarcinomas of the gastroesophageal junction (GEJ) are low,
      because these tumors are generally in an advanced stage by the time they are
      detected. Chromosomal regions 1q32, 7q21, and 8p22 display critical alterations
      in GEJ cancers; however, the genes underlying alterations in these genomic areas
      are largely unknown. To delineate overexpressed genes, we performed array
      comparative genomic hybridization (aCGH) and mRNA expression analysis of 15 GEJ
      adenocarcinoma samples using a fine-tiling cDNA array covering chromosome
      segments 1q31.3~q41 (193.9-215.8 Mb: 21.9 Mb), 7q11.23~q22.1 (72.3-103.0 Mb: 30.7
      Mb), and 8p23.1~p21.3 (11.1-20.7 Mb: 9.6 Mb). Based on a mRNA overexpression
      criterion, 11 genes were selected: ELF3 and SLC45A3 on 1q; CLDN12, CDK6, SMURF1,
      ARPC1B, ZKSCAN1, MCM7, and COPS6 on 7q; and FDFT1 and CTSB on 8p. The protein
      expression levels were subsequently determined by immunohistochemical analysis of
      the cancer samples. There was a significant correlation between genomic
      amplification, mRNA, and protein expression or overexpression for CDK6, a cell
      cycle regulator on 7q21.2 (92.1 Mb; P<0.01); other genes showed less stringent
      associations. In conclusion, using a straightforward approach we constructed a
      targeted gene profile for GEJ adenocarcinomas.

PMID- 19167611
TI  - JAK2 V617F/C618R mutation in a patient with polycythemia vera: a case study and
      review of the literature.
AB  - The acquired Janus kinase 2 (JAK2) V617F mutation shows a high frequency in
      diverse BCR/ABL-negative chronic myeloproliferative disorders (CMPD), and it is
      typically associated with polycythemia vera (PV). The frequency of JAK2 V617F
      mutation is about 90% in patients with PV, 50-60% in patients with essential
      thrombocythemia (ET), primary myelofibrosis (PMF), and less in patients with
      other myeloid neoplasms, while extremely rare in lymphoid malignancies. About 20
      kinds of novel mutations of JAK2 other than V617F have been reported recently in
      the literature. Among these mutations, only one case of JAK2 V617F/C618R has been
      reported in a 67-year-old patient with PV. Here, we report a rare case of JAK2
      V617F/C618R in a 41-year-old Korean male patient with review of the relevant
      literature on JAK2 mutations other than V617F. Although the frequency of JAK2
      mutations other than the V617F is very low, this study emphasizes the need for
      assiduous analysis of the JAK2 gene to characterize new mutations, to determine
      their frequency, and to improve understanding of the clinical phenotypes as well
      as prognostic and biologic features associated with these mutations.

PMID- 19167612
TI  - Poor outcome in a pediatric patient with acute myeloid leukemia associated with a
      variant t(8;21) and trisomy 6.
AB  - RUNX1T1/RUNX1 (formerly ETO/AML1) is a molecular marker that is usually
      associated with a favorable outcome in both pediatric and adult patients with
      acute myeloid leukemia (AML). We describe a 10-year-old girl with AML associated
      with an RUNX1T1/RUNX1 fusion. The patient's karyotype at the time of diagnosis
      was 46,X,-X,t(4;21;8)(q25;q22;q22),+6. She had an early relapse while being
      treated on a standard protocol and had significant difficulty in attaining a
      second remission. She subsequently underwent a matched related donor bone marrow
      transplant, but a second bone marrow relapse with extensive extramedullary
      disease followed on day +199. Cytogenetic analysis at second relapse showed
      evidence of clonal evolution in the form of a highly complex karyotype with
      numeric and structural abnormalities in addition to the t(4;21;8) and trisomy 6
      detected in the diagnostic sample. Trisomy 6 is an uncommon cytogenetic
      abnormality in myeloid diseases. As a sole abnormality, it has been associated
      mainly with myelodysplastic syndrome and AML. The presence of this novel variant
      of t(8;21)(q22;q22) associated with trisomy 6 may have abrogated the usual
      favorable prognosis associated with RUNX1T1/RUNX1 in AML.

PMID- 19167613
TI  - Inactivation of p53 and amplification of MYCN gene in a terminal lymphoblastic
      relapse in a chronic lymphocytic leukemia patient.
AB  - B-cell chronic lymphocytic leukemia (CLL) is an incurable disease with a highly
      variable clinical course. A proportion of patients eventually progress to a
      higher stage of malignancy. A recent association has been observed between the
      presence of aberrant somatic hypermutations in leukemic cells (hypermutations
      occurring outside of the immunoglobulin locus) and the transformation to a
      diffuse large B-cell lymphoma or prolymphocytic leukemia. In this study, we
      report on the rarely observed blastic transformation in a CLL patient who had
      previously been shown to harbor aberrant somatic hypermutations in the TP53 tumor
      suppressor gene (Mol Immunol 2008;45:1525-29). The enzyme responsible, the
      activation-induced cytidine deaminase, was still active within the
      transformation, as evidenced by the ongoing class-switch recombination of
      cytoplasmic immunoglobulins. The transformation was accompanied by a complete p53
      inactivation, as well as complex karyotype changes including prominent
      amplification of MYCN oncogene. Our case-study supports the view that the
      aberrant somatic hypermutation is associated with transformation of CLL to a more
      aggressive malignancy.

PMID- 19167614
TI  - A new chromosomal three-way rearrangement involving MLL masked by a
      t(9;19)(p11;p13) in an infant with acute myeloid leukemia.
AB  - Infants diagnosed with acute myelogenous leukemia (AML) are likely to have
      subtypes M4 or M5 characterized by 11q23 abnormalities like a t(9;11)(p22;q23).
      Detection of all possible types of chromosomal abnormalities, including mixed
      lineage leukemia (MLL) gene rearrangements at 11q23, is of importance for the
      identification of biological subgroups, which might differ in drug resistance
      and/or clinical outcome. Here, we report the clinical, conventional banding and
      molecular cytogenetics data of a 6-month-old boy with an AML-M5 presenting with a
      unique cryptic rearrangement involving the MLL gene: a three-way
      t(9;19;11)(p11.2;p13.1;q23).

PMID- 19167615
TI  - Development of AML with t(8;21)(q22;q22) and RUNX1-RUNX1T1 fusion following
      Philadelphia-negative clonal evolution during treatment of CML with Imatinib.

PMID- 19167616
TI  - Clonal chromosome aberrations in a sialoblastoma.

PMID- 19167617
TI  - Forward medical care and the military emergency medicine workforce: too much
      demand and not enough supply?

PMID- 19167618
TI  - Images in emergency medicine. Facial necrotizing fasciitis.

PMID- 19167619
TI  - Images in emergency medicine. Bilateral rupture of quadriceps tendons.

PMID- 19167621
TI  - 911.

PMID- 19167622
TI  - Annals of Emergency Medicine Journal Club. Out-of-hospital continuous positive
      airway pressure ventilation versus usual care in acute respiratory failure: a
      randomized controlled trial answers to the September 2008 Journal Club questions.

PMID- 19167623
TI  - Images in emergency medicine. Pyogenic vertebral osteomyelitis with bilateral
      paravertebral abscesses.

PMID- 19167624
TI  - Images in emergency medicine. Osteochondroma..

PMID- 19167625
TI  - Fortuitous effect of TASER shock misleading.

PMID- 19167626
TI  - Role of likelihood ratios in interpreting scoring systems used as predictive
      tools.

PMID- 19167628
TI  - Halo sign is neither sensitive nor specific for cerebrospinal fluid leak.

PMID- 19167629
TI  - The patient-centered medical home model.

PMID- 19167630
TI  - Definition of democracy in emergency medicine practice.

PMID- 19167631
TI  - Role of ryanodine receptor as a Ca2(+) regulatory center in normal and failing
      hearts.
AB  - Abnormal Ca2(+) cycling is important in various cardiac diseases. Evidence has
      accumulated that dysregulation of Ca2(+) release from the ryanodine receptor
      (RyR2) plays a significant role in cardiac dysfunction. Spontaneous Ca2(+)
      release through RyR2 during diastole decreases sarcoplasmic reticulum (SR) Ca2(+)
      content, and also induces delayed after depolarization (DAD) as a substrate for
      lethal arrhythmia. Several disease-linked mutations in the RyR have been reported
      in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) or
      arrythmogenic right ventricular cardiomyopathy type 2 (ARVC2). The unique
      distribution of these mutation sites has produced the concept that the
      interaction among the putative regulatory domains within the RyR may play a key
      role in regulating the channel opening, and that there seems to be a common
      abnormality in the channel disorder between heart failure and CPVT/ARVC2. We
      review here the considerable body of evidence regarding defective channel gating
      of RyR2 in the pathogenesis of heart failure and lethal arrhythmia.

PMID- 19167632
TI  - Effect of a single bout of moderate exercise on glucose uptake in type 2 diabetes
      mellitus.
AB  - BACKGROUND AND PURPOSE: Hypoglycemia during exercise is a serious problem in
      diabetic patients during cardiac rehabilitation, whereas normal subjects rarely
      experience hypoglycemia. Inappropriate glucose uptake by working muscles may be
      responsible. However, the precise characteristics of glucose uptake during
      exercise have not been fully studied. We have investigated the effect of acute
      exercise on glucose uptake in diabetic patients. METHODS: Nine type 2 diabetic
      patients (age, 57 +/- 6 years; HbA1c, 7.7 +/- 1.3%) performed exercise at an
      intensity of anaerobic threshold for 15 min. Glucose utility was determined using
      euglycemic hyperinsulinemic clamp technique. Glucose infusion rate (GIR) was
      calculated throughout the exercise and recovery session. RESULTS: Average GIR at
      rest was 3.4 +/- 1.6 mg/(kg(BW)min). Fifteen minutes after starting exercise, it
      increased significantly (6.6 +/- 2.4, p < 0.001). Thirty minutes after cessation
      of exercise, GIR decreased significantly (4.8 +/- 1.9, p < 0.05) compared with
      peak value. Increase in GIR was greater as BMI or body fat ratio became greater
      (r=0.608 and 0.475). There was a weak correlation (r=0.344) between HbA1c and GIR
      improving ratio (GIR during exercise x 100/GIR at rest). CONCLUSIONS: Glucose
      uptake was revealed to augment significantly within 15 min after the commencement
      of exercise. This improvement was more obvious in patients with greater body
      weight, fat accumulation, and poorer diabetic control.

PMID- 19167633
TI  - The strategy of immune globulin resistant Kawasaki disease: a comparative study
      of additional immune globulin and steroid pulse therapy.
AB  - BACKGROUND: We compared the clinical utility of additional intravenous immune
      globulin (IVIG) therapy with the clinical utility of steroid pulse therapy in
      patients with IVIG-resistant Kawasaki disease. METHODS: We enrolled 164 patients
      with Kawasaki disease who were treated with a single dose of IVIG (2 g/kg) and
      aspirin (30 mg/kg per day). Twenty-seven of these patients (16%) were resistant
      to the initial IVIG treatment. We compared the effectiveness of treatment
      strategies for the initial IVIG-resistant 27 patients, 14 of these patients were
      treated with additional IVIG therapy, and the other 13 patients were treated with
      steroid pulse therapy (methylprednisolone 30 mg/kg per day for 3 days). RESULTS:
      Three patients in the group receiving additional IVIG treatment had coronary
      artery aneurysms (21.4%), no patients had coronary artery aneurysm in the steroid
      pulse therapy group; the difference in the incidence of coronary artery aneurysm
      was not statistically significant. The duration of high fever after additional
      treatment in the steroid pulse therapy group (1 +/- 1.3 days) was significantly
      shorter than that in the additional IVIG treatment group (3 +/- 2.4 days; P <
      0.05). The medical costs were significantly lower in the steroid pulse therapy
      group than in the additional IVIG treatment group. CONCLUSION: Steroid pulse
      therapy was useful to reduce the fever duration and medical costs for patients
      with Kawasaki disease. Steroid pulse therapy and additional IVIG treatment were
      not significantly different in terms of preventing the development of coronary
      artery aneurysm.

PMID- 19167634
TI  - The clinical and hemodynamic factors that influence the concentrations of
      biomarkers of myocyte injury measured by high sensitive assay PATHFAST.
AB  - BACKGROUND: Subclinical myocyte injury plays an important role in the progression
      of congestive heart failure. However, the clinical and hemodynamic factors that
      influence the concentrations of biomarkers of myocyte injury have not been
      clarified. METHODS: Blood was sampled during diagnostic cardiac catheterization
      from 108 consecutive patients without acute coronary syndrome and acute cardiac
      decompensation. The serum concentrations of B-type natriuretic peptide (BNP),
      cardiac troponin I (cTnI), creatine kinase (CK)-MB, and myoglobin were measured
      simultaneously by high sensitive PATHFAST assay. Single and multiple variable
      regression analyses were carried out in search of correlations between clinical
      and hemodynamic variables and concentrations of biomarkers. RESULTS: By multiple
      variable analysis, hemoglobin concentration, pulmonary capillary wedge pressure
      (PCWP), left ventricular (LV) ejection fraction, and estimated glomerular
      filtration rate (GFR) were independently correlated with a BNP concentration >=
      median 72.1 pg/ml. The only factors independently correlated with a concentration
      of cTnI >= median 0.01 ng/ml were PCWP and estimated GFR. Cardiac index emerged
      as a single, powerful, independent correlate of CK-MB concentration >= median
      0.66 ng/ml, and estimated GFR emerged as a single independent correlate of
      myoglobin concentration >= median 40.1 ng/ml. CONCLUSIONS: Clinical and
      hemodynamic factors influence the concentrations of BNP, cTnI, CK-MB, and
      myoglobin. These factors should be considered when interpreting the
      concentrations of these biochemical markers.

PMID- 19167635
TI  - Percutaneous mitral valvotomy versus closed surgical commissurotomy. Up to 15
      years of follow-up of a prospective randomized study.
AB  - BACKGROUND: Immediate and intermediate term results of percutaneous mitral
      valvotomy (PMV) are comparable to closed surgical commissurotomy (CSC). We aimed
      at exploring this relation in the long term. METHODS: Previously, we randomized
      40 consecutive patients with moderate to severe mitral stenosis [defined as
      mitral valve area (MVA) less than 1.5 cm2] to undergo either PMV (PMV group = 20
      patients) or CSC (CSC group = 20 patients). For all patients, full
      echocardiographic assessment was performed before the procedure/operation.
      Patients assigned to PMV underwent the double balloon technique.
      Echocardiographic assessment was done following both procedures before discharge
      and repeated 1 and 6 months later. Echocardiographic follow-up was performed,
      thereafter, on a yearly basis for up to 15 years, with a mean follow-up period of
      99 +/- 12 months. RESULTS: Immediate echocardiographic results showed no
      statistically significant difference between the 2 groups regarding the final MVA
      or mean diastolic gradient across the mitral valve. Two patients dropped out from
      the CSC group and one from the PMV group. MVA was 1.8 +/- 0.3 cm2 versus 1.8 +/-
      0.4 cm2 (p > 0.05) and mean diastolic pressure gradient across the mitral valve
      was 7 +/- 4 mmHg versus 6.6 +/- 4 mmHg (p > 0.05) in the PMV and CSC groups,
      respectively. Mitral restenosis occurred in 5 (26.3%) patients in the PMV group
      versus 5 (27.8%) patients in the CSC group (p > 0.05). Kaplan-Meier curves for
      restenosis-free survival showed no difference between the 2 groups. CONCLUSION:
      PMV achieves comparable results to CSC both in the short and long term.

PMID- 19167636
TI  - A randomized study on the efficacy of intravenous cibenzoline and pilsicainide
      administered prior to electrical cardioversion in patients with lone paroxysmal
      and persistent atrial fibrillation.
AB  - METHODS AND RESULTS: This study included 68 patients (47 men, 21 women, mean age
      69 years) in whom atrial fibrillation (AF) recurred immediately after electrical
      cardioversion (EC) was performed with no antiarrhythmic drugs. After
      administration of cibenzoline (Cib, 70 mg) or pilsicainide (Pil, 50 mg) on a
      randomized basis, all patients again underwent EC at the same energy as that
      prior to administration of antiarrhythmic drugs. We compared the efficacy of Cib
      (n = 35) and Pil (n = 33), and examined factors affecting successful
      cardioversion in patients treated with Cib. These patients were divided into a
      successful group (Group A) and an unsuccessful group (Group B). The success rate
      of EC at the same energy after intravenous Cib administration (77%) was
      significantly greater than that after intravenous Pil administration (42%) (p <
      0.01). In patients treated with Cib, AF duration was significantly greater in
      Group B (55.8 +/- 48.2 h) than in Group A (29.1 +/- 17.0 h) (p < 0.05). Plasma
      concentrations of atrial natriuretic peptide (ANP) during AF and the ratio of ANP
      level during AF to that during sinus rhythm were also significantly greater in
      Group A (110.9 +/- 69.7 pg/ml and 3.9 +/- 2.8, respectively) than in Group B
      (58.2 +/- 36.1 pg/ml and 1.8 +/- 0.9, respectively) (both, p < 0.05). In patients
      treated with Pil, AF duration was also significantly greater in Group B (59.7 +/-
      44.6h) than in Group A (19.6 +/- 21.7 h) (p < 0.05), and the ratio of ANP level
      during AF to that during sinus rhythm was significantly greater in Group A (3.5
      +/- 2.6) than in Group B (1.7 +/- 0.9) (p < 0.05). CONCLUSIONS: In patients with
      AF previously refractory to conventional EC, intravenous Cib administration was
      more effective in restoring sinus rhythm with EC than intravenous Pil
      administration. The capacity of ANP secretion during AF tachycardia may be a
      predictive indicator for the prevention of AF recurrence in electrically
      remodeled atria.

PMID- 19167637
TI  - Important parameters in the detection of left main trunk disease using stress
      myocardial perfusion imaging.
AB  - OBJECTIVES: We sought noninvasively to diagnose left main trunk (LMT) disease
      using myocardial perfusion imaging (MPI). METHODS: Five hundred and eight
      patients with suspected coronary artery disease (CAD) underwent both stress MPI
      and coronary angiography. The extent and severity of perfusion abnormalities were
      assessed using a 20-segment model. In addition, perfusion defects in both left
      anterior descending and left circumflex arterial territories were defined as a
      left main (LM) pattern defect, and those in 3-coronary arterial territories as a
      3-vessel pattern defect. RESULTS: In 42 patients with LMT disease, a summed
      stress score (19.4 +/- 10.0 vs. 13.5 +/- 10.0; p < 0.0001) and a summed rest
      score (12.1 +/- 9.7 vs. 7.0 +/- 7.8; p = 0.002) were greater than in 466 patients
      without LMT disease, while a summed difference score was similar (7.3 +/- 7.7 vs.
      6.5 +/- 6.1; p = NS). The prevalence of an LM-pattern defect was low in both
      groups (12% vs. 8%; p = NS). However, a 3-vessel pattern defect (33% vs. 7%; p <
      0.0001), lung uptake of radiotracers (38% vs. 11%; p < 0.0001), and transient
      ischemic dilation (31% vs. 13%; p = 0.003) were more frequently observed in
      patients with LMT disease than in those without. Logistic regression analysis
      showed that a 3-vessel pattern defect (OR=3.5, 95% CI = 1.4-8.8; p = 0.007), lung
      uptake of radiotracers (OR = 2.5, 95% CI = 1.1-5.7; p = 0.03), and previous
      myocardial infarction (MI) (OR = 2.4, 95% CI = 1.0-5.7; p = 0.05) were the most
      important parameters to detect LMT disease. After excluding 163 patients with
      previous MI, a repeat analysis revealed that lung uptake of radiotracers (OR =
      8.2, 95% CI = 2.3-29.2; p = 0.001) and an LM-pattern defect (OR = 6.3, 95% CI =
      1.4-27.2; p < 0.02) were independent predictors for LMT disease. CONCLUSION: In
      the identification of LMT disease, lung uptake of radiotracers was a single best
      parameter, which was independent of the presence or absence of previous MI.

PMID- 19167638
TI  - Adrenergic receptor polymorphisms in patients with stress (tako-tsubo)
      cardiomyopathy.
AB  - BACKGROUND: Stress (tako-tsubo) cardiomyopathy (SC) is a newly reported condition
      afflicting older women, characterized by acute left ventricular (LV) systolic
      dysfunction, triggered by emotionally and physically stressful events, and
      occurring without significant coronary obstruction. Sympathetic nervous system
      hyperactivity has been implicated in the pathophysiology of SC. Single nucleotide
      polymorphisms involving the adrenergic receptors (AR) might result in
      susceptibility to SC. METHODS: Forty-one female SC patients were identified aged
      34-89 years (mean 65) and were compared with 43 control females of similar age
      with respect to AR genotype frequencies for B1 receptor (amino acid positions 389
      and 49) and alpha 2c receptor (deletion 322-325). RESULTS: For SC patients,
      initial LV ejection fraction was 32 +/- 10% vs. 62 +/- 11% in control patients, p
      < 0.05. Genotype frequencies for SC patients vs. controls were B1 389 Arg/Arg
      (0.49 vs. 0.51), B1 389 Arg/Gly (0.49 vs. 0.49), B1 389 Gly/Gly (0.02 vs. 0), B1
      49 Ser/Ser (0.88 vs. 0.81), B1 49 Ser/Gly (0.12 vs. 0.16), B1 49 Gly/Gly (0 vs.
      0.02), alpha 2c Wt/Wt (0.93 vs. 0.86), and alpha 2c Wt/Del 322-325 (0.07 vs.
      0.14); p = ns for all comparisons. CONCLUSIONS: Genotype polymorphism frequencies
      for B1 receptor (amino acid positions 389 and 49) and alpha 2c receptor (deletion
      322-325) are not significantly different in SC patients compared to female
      controls. These data suggest that these AR polymorphisms do not mediate the
      sympathetic nervous system hyperactivity in SC patients.

PMID- 19167639
TI  - Early atorvastatin therapy improves cardiac function in patients with acute
      myocardial infarction.
AB  - BACKGROUND: A number of experimental and clinical studies have demonstrated a
      cardioprotective effect of statins; however, the effect of atorvastatin on
      cardiac function in patients with an acute myocardial infarction (AMI) has not
      been established. METHODS AND RESULTS: Thirty consecutive patients with an AMI
      (16 males and 14 females) were enrolled. All the patients underwent successful
      percutaneous coronary intervention in the early phase after the onset of an AMI.
      Patients with a total cholesterol level > 200mg/dL on admission (n = 14) were
      assigned to the atorvastatin group. They began taking 10 mg of atorvastatin daily
      within 48 h after the onset of the AMI, while the other patients (n = 16) did not
      receive atorvastatin and served as the control group. Echocardiography and blood
      sampling to measure brain natriuretic peptide (BNP) and atrial natriuretic
      peptide (ANP) levels were repeated on the 2nd day (2D), 3 weeks (3W), 12 weeks
      (12W), and 24 weeks (24W) after the onset of the AMI. The percentage of patients
      with a high BNP level (BNP > 20 pg/mL) was significantly decreased from 2D to 24W
      in the atorvastatin group, but not in the control group (100 to 57% in the
      atorvastatin group, p < 0.05; 100 to 80% in the control group, n.s.). Similar
      results also occurred with respect to the ANP level (ANP > 40 pg/mL) (62 to 21%
      in the atorvastatin group, p < 0.05; 57 to 40% in the control group, n.s.). The
      left ventricular ejection fraction was significantly higher in the atorvastatin
      group than the control group at 3W (66.0 +/- 7.8% vs. 56.5 +/- 11.8%, p < 0.05)
      and 24W (67.5 +/- 9.2% vs. 59.7 +/- 9.8%, p < 0.05). In the atorvastatin group,
      the left ventricular systolic diameter was significantly decreased at 24W
      compared with that at 2D (37.1 +/- 8.0 mm to 31.4 +/- 6.5 mm, p < 0.05).
      CONCLUSIONS: Initiation of atorvastatin in the early phase of an AMI has
      beneficial effects on cardiac function, probably by improving left ventricular
      remodeling.

PMID- 19167640
TI  - Association between cardiac function and metabolic factors including adiponectin
      in patients with acute myocardial infarction.
AB  - BACKGROUND: Although several clinical studies have evaluated plasma adiponectin
      levels in response to chronic heart failure, little is known about the relation
      between cardiac function and metabolic factors including adiponectin in patients
      with acute myocardial infarction (AMI). METHODS AND RESULTS: We analyzed 50
      consecutive patients with AMI who had undergone successful coronary stent
      implantation. Echocardiography and blood sampling were performed at 1 week and 6
      months after AMI. Blood was analyzed with regard to brain natriuretic peptide
      (BNP) and metabolic factors including plasma levels of adiponectin, lipid
      profile, and hemoglobin A1c (HbA1c). Plasma adiponectin levels were significantly
      increased at 6 months (7.3 +/- 4.9 MUg/ml) compared to those at 1 week (6.1 +/-
      3.7). BNP (from 156 +/- 151 to 96 +/- 124 pg/ml) significantly decreased. In
      addition, BNP at 6 months was positively correlated with plasma adiponectin
      levels at 1 week (y = 0.019 x -23.1, r = 0.537, P = 0.002), while BNP at 6 months
      was not associated with maximal creatinine kinase after AMI. A multiple
      regression analysis was performed to analyze the relationship between BNP at 6
      months and metabolic factors (plasma levels of adiponectin, lipid profile, HbA1c,
      blood pressure, age, sex, and body mass index) at 1 week after AMI. BNP at 6
      months was most closely correlated with plasma levels of adiponectin at 1 week (P
      = 0.045). CONCLUSIONS: Among the metabolic factors examined, a higher adiponectin
      level at 1 week is the predictor of a higher BNP as one marker of cardiac
      dysfunction at 6 months after AMI.

PMID- 19167642
TI  - Screening method for severe sleep-disordered breathing in hypertensive patients
      without daytime sleepiness.
AB  - The high prevalence of sleep-disordered breathing (SDB) in hypertensive patients
      has been well studied. However, regular screening of SDB in these patients is not
      performed routinely as the diagnostic procedures are both time-consuming and
      labour-intensive. Overnight portable device screening is useful, but is sometimes
      not acceptable for asymptomatic SDB patients. We evaluated the usefulness of
      daytime 30-min recording with a portable recording device during pulse wave
      velocity (PWV) measurement sessions as a screening method for detection of
      asymptomatic SDB in hypertensive patients. Eighty-one hypertensive patients
      underwent 30-min daytime screening session using a Type III portable recording
      device during PWV measurement. Each screening session was followed by full
      overnight Level I polysomnography (PSG). The screening session included
      recordings of airflow (mouth-nose), chest movement, oximetry, and
      electrocardiography. The correlation coefficient between respiratory disturbance
      index (RDI) by screening session and apnea-hypopnea index (AHI) by PSG was 0.64.
      Using AHI >= 30 as diagnostic of severe SDB, 47 of 80 patients had the disorder
      based on PSG results. Using an RDI cut-off value of 22, the sensitivity and
      specificity for detection of severe SDB were 86.1% and 64.5%, respectively.
      Daytime 30-min recording with a portable device for apnea detection during PWV
      recording is useful for screening of asymptomatic severe SDB in hypertensive
      patients.

PMID- 19167641
TI  - Beneficial effects of beta-blockers and angiotensin-converting enzyme inhibitors
      in Duchenne muscular dystrophy.
AB  - BACKGROUND: Patients with Duchenne muscular dystrophy (DMD) often have severe
      heart failure with a high mortality rate. Most DMD patients with cardiomyopathy
      became symptomatic in their early to middle teens and usually die of congestive
      heart failure within 2-3 years from the onset of symptoms. It has been reported
      that the combination of an angiotensin-converting enzyme (ACE) inhibitor and a
      beta-blocker has additive benefits in patients with heart failure. The aim of
      this study was to assess whether the combination of an ACE inhibitor and a beta
      blocker is associated with long-term survival of DMD patients with left
      ventricular (LV) dysfunction. METHODS: We retrospectively analyzed the outcomes
      of 52 DMD patients who had begun treatment for heart failure with an ACE
      inhibitor and a beta-blocker at National Yakumo Hospital during the period from
      1992 to 2005. All patients used wheelchairs in their daily lives. Patients were
      classified as symptomatic or asymptomatic at the initiation of treatment with
      these two drugs. Twelve patients who had already had apparent symptoms due to
      heart failure were enrolled in a treatment group. Forty patients who had no
      symptoms with reduced LV ejection fraction (<= 45% in echocardiography) were
      enrolled in a prevention group. RESULTS: Five-year and 7-year survival rates of
      all patients were 93 and 84%, respectively. In the treatment group, 5-year and 7
      year survival rate were 81 and 71%, respectively. Survival rate became zero at
      10.9 years. In the prevention group, 5-year and 7-year survival rates were 97 and
      84%, respectively, and 10-year survival rate was 72%. Nine patients in the
      prevention group remained event-free over 10 years. CONCLUSIONS: In this study,
      the combination of an ACE inhibitor and a beta-blocker had a beneficial effect on
      long-term survival of DMD patients with heart failure. The treatment was
      particularly effective for asymptomatic patients with LV dysfunction.

PMID- 19167643
TI  - In early-stage diabetic retinopathy, risk of cardiac events after implantation of
      sirolimus-eluting stent is higher than after coronary artery bypass surgery.
AB  - BACKGROUND: Patients with diabetic retinopathy (DR) have an increased risk of
      death from coronary heart disease and myocardial infarction. The purpose of this
      study was to compare the outcomes of revascularization strategies (sirolimus
      eluting stent [SES] and coronary artery bypass surgery [CABG]) in patients with
      DR according to the stage of retinopathy: non-proliferative retinopathy (NPDR)
      and proliferative retinopathy (PDR). METHODS: From April 2004 until February
      2007, 627 patients including 51 NPDR and 62 PDR patients underwent SES
      implantation. For each retinopathy group, a historical comparison group at the
      same stages of retinopathy undergoing CABG was selected. Cardiac events were
      defined as a composite of cardiac death, myocardial infarction, and repeat
      revascularization. RESULTS: The average follow-up from the time of the initial
      revascularization was 27.7 +/- 8.5 months for NPDR-SES patients, 69.6 +/- 36.6
      months for NPDR-CABG patients, 26.4 +/- 9.7 months for PDR-SES patients, and 68.3
      +/- 44.2 months for PDR-CABG patients; and Kaplan-Meier estimates of the
      percentages of events at 24 months were 47.0%, 22.8%, 28.5%, and 26.0%. Kaplan
      Meier curves for cardiac events differed significantly between the SES group and
      the CABG group in NPDR patients (p = 0.04), whereas the curves did not differ
      significantly between the two groups of PDR patients. The adjusted hazard ratio
      of SES implantation for cardiac events in the entire group of DR patients was
      1.75 (95% confidence interval [CI] 1.02-3.00, p = 0.04). CONCLUSIONS: SES
      implantation is not a suitable method of revascularization in DR patients,
      especially in NPDR patients. CABG may become the first-choice revascularization
      technique for these patients.

PMID- 19167644
TI  - Quantitative measurement of mitral valve coaptation in functional mitral
      regurgitation: In vivo experimental study by real-time three-dimensional
      echocardiography.
AB  - BACKGROUND: The degree of mitral valve (MV) coaptation should be an important
      parameter in the assessment of functional mitral regurgitation (MR). This study
      aimed to quantify the degree of MV coaptation in experimental models of
      functional MR caused by acute left ventricular (LV) pressure overload, using real
      time three-dimensional (3D) echocardiography. METHODS AND RESULTS: Using canine
      models, LV pressure overload was induced by staged ascending aortic banding.
      Echocardiographic examinations were performed before and during the aortic
      banding. By using a novel software system for 3D quantification (REALVIEW(r)),
      the annulus and leaflet were traced manually both at the onset of MV closure and
      at the maximum MV closure. The coaptation index was calculated by the following
      formula: [(3D tenting surface area at the onset of MV closure-3D tenting surface
      area at the maximum MV closure)/3D tenting surface area at the onset of MV
      closure] x 100. MR area gradually increased with the decrease in coaptation index
      during progressively exacerbated aortic banding. MR area was significantly
      correlated with the coaptation index. A coaptation index < 12 had a high
      sensitivity and specificity in the presence of significant MR. CONCLUSIONS: The
      degree of MV coaptation can be quantified using 3D echocardiography. The
      coaptation index should be a useful parameter in the assessment of functional MR.

PMID- 19167645
TI  - Simvastatin reduces myocardial infarct size via increased nitric oxide production
      in normocholesterolemic rabbits.
AB  - OBJECTIVE: Statins have been reported to be protective against myocardial
      infarction (MI). Moreover, statin drugs upregulate nitric oxide (NO) in coronary
      artery independent of lipid-lowering effects. However their precise mechanism for
      MI-protection is unclear. We investigated the effect of lipophilic statin
      administration in a normocholesterolemic rabbit MI model. METHODS: Nomega-nitro-L
      arginine methylester (L-NAME, 10 mg/kg) or vehicle alone was intravenously
      administered 20 min before inducing ischemia, followed by intravenous
      administration of simvastatin (5 mg/kg) or saline 10 min before ischemia. Rabbits
      then underwent 30 min of coronary occlusion followed by 48 h of reperfusion. The
      at-risk and infarct areas were calculated as a percentage of the total left
      ventricular slice area. RESULTS: Determination of infarct size revealed that pre
      ischemic treatment with simvastatin reduced infarct size (30.5 +/- 4%) in
      comparison to controls (45.0 +/- 3%) (P < 0.05). This infarct size-reducing
      effect of simvastatin could be completely abrogated by pretreatment with L-NAME
      (42.0 +/- 4%). CONCLUSIONS: Pre-ischemic treatment with simvastatin reduces MI
      size via NO production. Simvastatin could be a useful drug for coronary artery
      disease patients without dyslipidemia as it has direct protective effects.

PMID- 19167646
TI  - Serum levels of remnant lipoprotein cholesterol and oxidized low-density
      lipoprotein in patients with coronary artery disease.
AB  - BACKGROUND: Oxidized low-density lipoprotein (OxLDL) and remnant lipoprotein play
      a crucial role in the development of atherosclerosis. Recently, a novel method
      for measuring remnant cholesterol levels (remnant lipoproteins cholesterol
      homogenous assay: RemL-C) has been established. However, the correlation between
      OxLDL and remnant lipoprotein, including RemL-C, has not been fully investigated.
      METHODS: We enrolled 25 consecutive patients with documented coronary artery
      disease (CAD) and 20 controls. Remnant-like particle cholesterol (RLP-C) and RemL
      C were used to determine the levels of remnant lipoprotein cholesterol. Serum
      levels of malondialdehyde-modified LDL (MDA-LDL) and OxLDL using a monoclonal
      antibody DLH3 (OxPC) were used to measure the concentration of circulating OxLDL.
      RESULTS: The CAD group had high levels of fasting glucose and glycosylated
      hemoglobin (HbA1c), and low levels of high-density lipoprotein cholesterol
      compared with the control group. Serum levels of total cholesterol or LDL
      cholesterol were not significantly different between the two groups. The levels
      of RemL-C (p = 0.035), MDA-LDL (p = 0.018), and MDA-LDL/LDL-C (p = 0.036) in the
      CAD group were significantly higher than those in the control group. The levels
      of RLP-C tended to be higher in the CAD group than those in the control group (p
      = 0.096). Positive correlations were demonstrated between remnant lipoprotein
      cholesterol and OxLDL (RLP-C and MDA-LDL/LDL-C, r = 0.45, p = 0.0024, RLP-C and
      OxPC, r = 0.51, p = 0.0005, RemL-C and MDA-LDL/LDL-C, r = 0.42, p = 0.0044, RemL
      C and OxPC, r = 0.43, p = 0.0043). Similar trends were observed in non-diabetic
      subjects and in subjects without metabolic syndrome. Positive correlations were
      also observed between RLP-C and RemL-C (r = 0.94, p < 0.0001) and between MDA
      LDL/LDL-C and OxPC (r = 0.40, p = 0.0074). CONCLUSIONS: These results suggest
      that the association between high levels of remnant lipoprotein cholesterol and
      high OxLDL levels might be linked to atherogenesis in patients with CAD.

PMID- 19167647
TI  - A health-related quality of life questionnaire in symptomatic patients with heart
      failure: validity and reliability of a Japanese version of the MRF28.
AB  - BACKGROUND: Major characteristics of symptomatic patients with heart failure are
      exercise intolerance, poor prognosis, and poor quality of life (QOL). However,
      most QOL questionnaires are applicable for patients with mild to moderate heart
      failure, and are not sufficiently sensitive to discriminate between patients with
      NYHA classes III and IV. Therefore, it is necessary to prepare a questionnaire
      focused on patients with severe heart failure. OBJECTIVES: We developed a
      Japanese version of the Maugeri Foundation Respiratory Failure (MRF28)
      questionnaire and assessed validity and reliability of MRF28 in heart failure
      patients. METHODS: The MRF28 questionnaire was evaluated in 124 patients with
      heart failure (NYHA classes: I, 24; II, 31; III, 52; IV, 17). Reliability was
      evaluated by internal consistency and test-retest reliability. Validity was
      determined by correlation with World Health Organization Quality of Life (WHOQOL)
      questionnaire and physiological parameters. RESULTS: The MRF28 showed high
      internal consistency and reproducibility. The total score and subscores were all
      increased with the progress of heart failure. The total score could differentiate
      patients among NYHA II, III, and IV, but could not between NYHA I and II.
      However, all subscores and total score changed consistently with changes in
      symptoms of heart failure. CONCLUSION: MRF28 is a valid and reliable disease
      specific questionnaire for assessing QOL in symptomatic patients with heart
      failure. Thus, this questionnaire may be useful for a QOL evaluation of patients
      with moderate to severe heart failure.

PMID- 19167648
TI  - The role of infection in the development of non-valvular atrial fibrillation: up
      regulation of Toll-like receptor 2 expression levels on monocytes.
AB  - Many studies have suggested that inflammation may participate in the pathogenesis
      of non-valvular atrial fibrillation (AF). However, it has been unknown by
      exposure to what the inflammation is caused. Recently, we reported that Toll-like
      receptor 2 (TLR2) level on monocytes was significantly up-regulated in viral and
      bacterial infections, but not in non-infectious inflammatory states. Our purpose
      was to test the hypothesis that expression of TLR2 levels may be up-regulated in
      patients with non-valvular AF. A total of 48 consecutive patients with non
      valvular AF who were hospitalized for catheter ablation were enrolled in this
      study. TLR2 levels were assayed by using flow-cytometric analysis and compared
      with volunteers in sinus rhythm (control group, n = 24). Additionally, C-reactive
      protein (CRP) and interleukin-6 (IL-6) levels were assayed, and the left atrial
      volume indexes (LAVI) in the non-valvular AF group were measured. The results
      demonstrated that TLR2 levels in the non-valvular AF group were significantly
      higher than in the control group (median, 4682 vs. 3866 sites/cell; P < 0.01).
      Moreover, non-valvular AF patients had significantly higher IL-6 levels than
      controls. However, there was no significant difference in CRP levels between the
      two groups. It was observed in 44 AF patients, in whom pulmonary vein isolation
      was confirmed to be successful, that the LAVI significantly diminished 1 month
      after ablation (median, 33.6 vs. 29.5 ml/m2; P < 0.001), but not the TLR2 and IL
      6 levels. Our results implied that an infectious inflammation may participate in
      the pathogenesis of non-valvular AF.

PMID- 19167649
TI  - Pilsicainide intoxication presenting as left ventricular dyssynchrony in a
      patient on hemodialysis.
AB  - We report here a case of pilsicainide intoxication presenting as left ventricular
      dyssynchrony in a patient who had been treated on hemodialysis. This is the first
      report that assessed cardiac function during pilsicainide intoxication by left
      ventriculography and right heart catheterization.

PMID- 19167650
TI  - A case of transient mid-ventricular akinesia (a variant form of Takotsubo
      cardiomyopathy) followed with I-123-beta-metyl-iodophenyl pentadecanoic acid and
      I-123-meta-iodobenzyl-guanidine myocardial scintigraphy.
AB  - A 67-year-old woman without history of heart disease was admitted with chest
      oppression. Her electrocardiogram (ECG) at the time of admission showed ST
      segment elevation in leads V2-V6. Cardiac ultrasound revealed severe hypokinesis
      in mid to apical portion of anterior wall. Emergent coronary angiography showed
      normal coronary arteries. Left ventriculography (LVG) revealed akinesis of mid
      portion of anterior and inferior wall with hyperkinesis of apex and basal portion
      of anterior and inferior wall. Cardiac ultrasound examination 3 months later
      revealed improvement in LV contraction without mid-ventricular akisesia. The LVG
      performed 6 months later showed no focal asynergy. In I-123-beta-metyl-iodophenyl
      pentadecanoic acid myocardial scintigraphy the discrepancy of uptake between
      apical and anterior and inferior wall of mid region (more uptake in apex) was
      reduced. Using I-123-meta-iodobenzyl-guanidine myocardial scintigraphy in acute
      phase, decreased uptake in the mid portion of anterior and inferior to lateral
      wall was seen in early and delayed images and that persisted through 6 months. As
      these findings resembled those of Takotsubo cardiomyopathy other than affected
      region, it is possible to say that basically they belong to same entity of
      disease but they are different in their phenotype.

PMID- 19167651
TI  - MRSA tricuspid valve infective endocarditis with multiple embolic lung abscesses
      treated by combination therapy of vancomycin, rifampicin, and
      sulfamethoxazole/trimethoprim.
AB  - A 26-year-old pregnant woman who was an intravenous drug user (IDU) was admitted
      to our hospital for the treatment of tricuspid valve infective endocarditis (IE)
      and lung abscesses due to methicillin-resistant Staphylococcus aureus (MRSA). We
      started to treat her with vancomycin (VCM) alone and then in combination with
      rifampicin (RFP), but her condition did not improve. Then we added
      sulfamethoxazole/trimethoprim (SMZ/TMP) to VCM and RFP. After that, she improved
      rapidly. In Japan, there are very few reports about tricuspid valve IE caused by
      MRSA in IDUs. This case suggests that the combination of VCM, RFP, and SMZ/TMP
      may be effective for the treatment of severe MRSA infections.

PMID- 19167652
TI  - Progressive atrial lead perforation developed 5 years after pacemaker
      replacement.
AB  - This report describes an asymptomatic case of atrial lead perforation which
      developed 5 years after pacemaker implantation. Although retrospective findings
      of computed tomography showed a screw-in atiral lead had already perforated 9
      months after the implantation, the lead protrusion on chest X-rays and pacing
      failure had not been noticed until another 3 years later. At first, this
      complication was managed conservatively, however, a lead perforation
      progressively developed and, as a result, open surgery was performed to remove
      the lead. We therefore should be aware of the potential occurrence of a
      progressive protrusion of a perforated lead.

PMID- 19167653
TI  - Society of Interventional Radiology 2007 annual meeting: presidential address.

PMID- 19167654
TI  - Behavioral correlates of biologic maturity of the cervix in adolescents.

PMID- 19167655
TI  - Trying to fit square pegs in round holes: eating disorders in males.

PMID- 19167656
TI  - Preventing HIV among adolescents in Sub-Saharan Africa.

PMID- 19167657
TI  - Factors that influence the rate of epithelial maturation in the cervix in healthy
      young women.
AB  - PURPOSE: To examine the longitudinal changes in the epithelial topography of the
      cervix in healthy young women; and to determine the sociodemographic, behavioral,
      and biological factors associated with the rate of cervical epithelial
      maturation. METHODS: Healthy young women were enrolled from October 2000 to
      September 2002 as part of a larger study of human papillomavirus (HPV). At
      interval visits, interviews, infection testing, and colpophotography (3% acetic
      acid; 10x, 16x magnifications) were performed. Areas of total cervical face and
      cervical immaturity, defined as columnar and early squamous metaplasia, were
      quantitatively measured using computerized planimetry. Cervical immaturity was
      expressed as percentage of total cervical face. This analysis includes the first
      consecutive 145 women with greater than 10% immaturity at baseline. The rate of
      cervical maturation was defined as change in percent-immaturity. Predictors
      included sociodemographics, sexual behaviors, and infections. Data analyses
      included multivariate generalized linear models with repeated measures. RESULTS:
      The baseline mean age was 17.8 years. Colpophotographs were available from 815
      total visits, representing 2.7 years mean follow-up per woman and 5.9-month mean
      intervals. Women began the study with a median of 39% immaturity and ended with
      8% immaturity. After adjusting for time and baseline percent-immaturity, an
      increased rate of cervical maturation was associated with oral contraceptive pill
      use (parameter estimate -.023, p =.04) and smoking (-.039, p =.01). CONCLUSIONS:
      Cervical maturation was documented during relatively short time periods for the
      vast majority of these women. Oral contraceptive pills and smoking may accelerate
      the maturational process, representing increased cell proliferation and thus a
      possible greater vulnerability to HPV.

PMID- 19167658
TI  - Disordered eating behaviors: what about boys?
AB  - PURPOSE: To determine the characteristics specific to boys with disordered eating
      behaviors (DEB) and the general context in which these DEB occur. METHOD: Data
      were drawn from the SMASH02 database, a survey carried out among post-mandatory
      school students in Switzerland aged 16-20 years in 2002. Only males (N=3890) were
      included, and were classified into into one of four groups based on their level
      of concern about weight/food and on their eating behaviors, as follows: group 1:
      one concern without behavior (N=862); group 2: more than one concern without
      behavior (N=361); group 3: at least one behavior (N=798); and a control group
      (N=1869), according to previously validated items. Groups were compared for
      personal, family, school, experience of violence, and health-compromising
      behaviors variables on the bivariate level. All significant variables were
      included in a multinomial logistic regression using Stata 9 software. RESULTS:
      About one-half of the boys reported either a concern or unhealthy eating
      behavior. Compared with the control group, boys from the three groups were more
      likely to be students and to report a history of sexual abuse, delinquency,
      depression, and feeling fat. In addition, boys from group 3 were more likely to
      report a history of dieting, early puberty, peer teasing, having experienced
      violence, frequent inebriation, and being overweight. CONCLUSION: DEB concern
      adolescent males more frequently than thought and seem to be integrated in a
      general dysfunctional context, in which violence is predominant. Adolescent males
      also need to be screened for DEB. Moreover, prevention programs should target the
      increasing social and media pressure regarding boys ideal body shape and raise
      public consciousness about this phenomenon.

PMID- 19167659
TI  - Effects of school health nursing education interventions on HIV/AIDS-related
      attitudes of students in Akwa Ibom State, Nigeria.
AB  - PURPOSE: One of the greatest challenges facing school nurses is that of
      identifying and using appropriate strategies to meet the health education needs
      of adolescents in regard to prevention of human immunodeficiency virus (HIV) and
      acquired immune deficiency syndrome (AIDS). This study examined the effects of
      HIV/AIDS preventive health education with parental involvement on students'
      attitude toward HIV/AIDS prevention in Akwa Ibom State, Nigeria. METHODS: The
      study population comprised students from three of nine secondary schools in the
      study area. The three schools were randomly assigned as Intervention Group 1
      (IG1), involving nurses only; Intervention Group 2 (IG2), involving both nurses
      and parents (IG2); and a control group. A pretest/post-test intervention design
      was used. A 29-item, validated questionnaire was the instrument for data
      collection. Sampling involved multistage and stratified random technique to
      select 120 subjects from each of the three selected schools, with a total of 360
      subjects representing 8.3% of the study population. From this number, 339 (94.2%)
      provided sufficient data for analysis. Data analysis involved analysis of
      covariance and the Scheffe post hoc test determined at the .05 significance
      level. RESULTS: Results show significant effect of intervention on students
      attitudes toward preventive measures (F = 234.27, p < .001 *). The intervention
      that involved nurses only was found to be a more potent strategy in providing
      favorable attitudes toward HIV/AIDS prevention (IG1 mean, 20.59; IG2 mean, 19.20;
      control mean, 12.34). Attitudes were influenced by older age but not by gender.
      CONCLUSION: Health education efforts aimed at improving HIV/AIDS-related
      attitudes should not only focus on children but also on parents so that they in
      turn could assist to improve on health workers' efforts in educating the
      children.

PMID- 19167661
TI  - Detecting HIV associated neurocognitive disorders in adolescents: what is the
      best screening tool?
AB  - PURPOSE: To examine the ability of the HIV-Dementia Scale (HDS) and Mini Mental
      State Exam (MMSE) to detect encephalopathy in adolescents living with human
      immunodeficiency virus (HIV) and/or acquired immunodeficiency syndrome (AIDS).
      METHOD: The study was based on chart review (N = 71) from 1999 to 2006,
      extracting data from psychological testing, disease classification, and
      demographic variables. HDS and MMSE scores were independent. Diagnosis of
      encephalopathy used American Academy of Neurology Criteria. Receiver Operating
      Characteristic Curves were plotted. RESULTS: Six patients had encephalopathy. The
      HDS identified five of these cases (83% sensitivity, 76% specificity). The MMSE
      identified three cases (50% sensitivity, 92% specificity). CONCLUSION: Based on
      the study results, the HDS appears to be clinically useful.

PMID- 19167660
TI  - Development of a directly observed therapy adherence intervention for adolescents
      with human immunodeficiency virus-1: application of focus group methodology to
      inform design, feasibility, and acceptability.
AB  - PURPOSE: To obtain input from adolescents with human immunodeficiency virus-1
      (HIV-1) infection to inform the design of a community-based modified directly
      observed therapy (MDOT) antiretroviral adherence intervention. METHODS: Pediatric
      AIDS Clinical Trials Group (PACTG) protocol 1036A conducted three focus groups
      with 17 adolescents aged 17-22 years (10 female, 65% African-American) from three
      geographically distinct US PACTG sites. Focus group sessions were scripted, audio
      taped, and transcribed verbatim. A coding dictionary was developed and validated;
      Ethnograph version 5.08 was used to summarize coded data across and within the
      three sites. Prevalent themes were identified via frequencies and are reported as
      percentages. RESULTS: Adolescents provided the following specific input: the MDOT
      provider should be familiar with the participant and empathic; the MDOT location
      should be mutually agreed on, flexible, and private; and participant and provider
      communication should be bidirectional, preferably by phone. Ideally the MDOT
      program should be continued until adolescents independently demonstrate adherence
      and should include a weaning phase as a test of skill acquisition. The most
      commonly endorsed barrier to the proposed program was that MDOT would be an
      invasion of privacy. Initially, after introduction to the purpose of the focus
      group, all but one adolescent expressed the belief that MDOT could benefit
      persons other than themselves; however, at the conclusion of the focus group
      discussion, a significant shift in openness to the intervention occurred, in that
      11 participants indicated they would consider participation in an MDOT program if
      such a program were offered. CONCLUSIONS: Focus group feedback clarified the
      feasibility, logistics, and patient concerns about the design and implementation
      of a proposed MDOT intervention for adolescents with HIV-1 infection who struggle
      with medication adherence.

PMID- 19167662
TI  - A human immunodeficiency virus risk reduction intervention for incarcerated
      youth: a randomized controlled trial.
AB  - PURPOSE: To evaluate, by gender, the impact of a structured, comprehensive risk
      reduction intervention with and without boosters on human immunodeficiency virus
      (HIV) knowledge, attitudes and behaviors in incarcerated youth; and to determine
      predictors of increasing HIV knowledge and reducing high-risk attitudes and
      behaviors. METHODS: This randomized controlled trial involved participants
      completing structured interviews at 1, 3, and 6 months. Repeated measures
      analysis of variance was used to analyze changes over time. The study was
      conducted in secure custody facilities and in the community. The study sample
      comprising 391 incarcerated youth, 102 female and 289 male aged 12-18, formed the
      voluntary sample. Participants were randomly assigned to one of three conditions:
      education intervention; education intervention with booster; or no systematic
      intervention. The outcome and predictor measures included the Rosenberg Self
      Esteem Scale, Youth Self Report, Drug Use Inventory, and HIV Knowledge, Attitudes
      and Behavior Scale. RESULTS: The 6-month retention rate was 59.6%. At 6 months,
      males in the education and booster groups sustained increases in knowledge scores
      (p < 0.001). Females in these groups sustained increased condom attitude scores
      (p = 0.004). Males in the booster group sustained increased prevention attitude
      scores (p = 0.017). Females in the booster group reported more consistent condom
      use (odds ratio [OR] = 4.20; 95% confidence interval [CI] = 1.81, 9.77). Age,
      gender, drug use, and psychological profiles were predictive of outcome.
      CONCLUSIONS: The intervention and boosters led to gender-specific improvements in
      knowledge, attitudes, and condom use. Result variations by gender underline the
      importance of gender issues in prevention interventions. Predictors of success
      were identified to inform future HIV education interventions.

PMID- 19167663
TI  - Effects of growth in family conflict in adolescence on adult depressive symptoms:
      mediating and moderating effects of stress and school bonding.
AB  - PURPOSE: To (1) examine growth in family conflict during adolescence as a
      predictor of depressive symptoms in early adulthood, (2) examine adult stressful
      life events as a possible mechanism linking prior family conflict with depressive
      symptoms, and (3) examine adolescent school bonding as a possible moderator of
      family conflict and stressful life events in relation to later depression.
      METHODS: Analyses used a latent variable growth curve modeling approach to
      examine longitudinal patterns in data from the Seattle Social Development
      Project. Assessments of a gender-balanced and ethnically diverse sample of 754
      participants were conducted from age 10 to age 27. RESULTS: Results show an
      increase in conflict each year between ages 14 and 18 for participating youth.
      High initial levels and growth in family conflict predicted adult stressful life
      events, which, in turn, predicted adult depressive symptoms, controlling for
      earlier risks of poverty and internalizing problems. Bonding to school in mid
      adolescence did not significantly change the associations among the variables in
      the model. CONCLUSIONS: Inhibiting the growth in family conflict over the course
      of adolescence may reduce the risk for some life stresses linked to depression in
      early adulthood. Although a test of the protective influence of school bonding
      during mid-adolescence was not significant, the study offers an example of how
      longitudinal patterns and protective factors can be analyzed.

PMID- 19167664
TI  - Mechanisms linking stressful life events and mental health problems in a
      prospective, community-based sample of adolescents.
AB  - PURPOSE: Stressful life events represent potent risk factors for the development
      of internalizing symptoms among adolescents. However the mechanisms linking
      stress to adolescent psychopathology remain inadequately understood. This study
      examined the role of emotion dysregulation as a mechanism linking stress to
      changes in internalizing symptoms among adolescents. METHODS: This study used a
      short-term longitudinal design. Stressful life events were assessed in a large
      diverse sample of adolescents (N = 1065), and emotion dysregulation and
      symptomatology outcomes were assessed at two subsequent time points. Structural
      equation modeling was used to examine the role of emotion dysregulation as a
      mediator of the association between stress and subsequent changes in
      internalizing symptoms. RESULTS: Emotion dysregulation mediated the relationship
      between stressful life events and changes in internalizing symptoms over time.
      Sobel's test indicated a significant indirect effect of stressful life events on
      subsequent symptoms of depression (z = 5.05, p < .001) and anxiety (z = 4.95, p <
      .001) through emotion dysregulation. CONCLUSIONS: Stressful life events appear to
      disrupt the adaptive processing of emotion among adolescents. Emotion
      dysregulation represents an intrapersonal mechanism linking stress to poor mental
      health outcomes. The implications for preventive interventions are discussed.

PMID- 19167665
TI  - From adolescent connections to social capital: predictors of civic engagement in
      young adulthood.
AB  - PURPOSE: This study examined the ability of adolescent connection in family and
      community contexts to promote an aspect of healthy youth development and
      transition into adulthood, civic engagement. METHODS: Data are from Wave 1 (1995)
      and Wave 3 (2001-2002) of the in-home interviews from the National Longitudinal
      Study of Adolescent Health. The sample for this study included 9130 young adults
      aged 18-26 years. Linear and logistic regression models were used to measure the
      influence of connection in family and community contexts (Wave 1) on outcomes of
      civic engagement in young adulthood (Wave 3). RESULTS: Stronger connection in all
      family and community contexts during adolescence predicted greater likelihood of
      voting, community volunteer service, involvement in social action/solidarity
      groups, education groups, and/or conservation groups, and endorsement of civic
      trust in young adulthood. Select connections in family and community contexts
      were also significant predictors of political voice/involvement and blood product
      donation. In a final multivariate model, frequency of shared activities with
      parent(s) and school connection during adolescence emerged as unique predictors
      of young adult civic engagement. CONCLUSIONS: Connections in family and community
      contexts during adolescence promote healthy youth development through
      facilitation of multiple aspects of civic engagement in young adulthood. The
      importance of these connections in fostering youth capacity to bond to a broader
      community construct is discussed.

PMID- 19167666
TI  - Patterns of risky behaviors associated with methamphetamine use among young Thai
      adults: a latent class analysis.
AB  - PURPOSE: Methamphetamine (MA) is the leading illicit drug in Thailand among youth
      and young adults. Sexual risk behaviors are associated with methamphetamine use,
      but few data are available on the daily context of methamphetamine use. We
      developed an inductive behavioral typology that young Thais engage in while using
      methamphetamine. METHODS: We conducted a cross-sectional study in Chiang Mai,
      Thailand, in 2005-2006 among 1,162 street-recruited methamphetamine smokers 18-25
      years of age. Data collected included sociodemographic characteristics, sexual
      behaviors, and drug use patterns. Latent class analysis was used to describe
      patterns of activities in which participants reported engaging directly after
      using MA. Logistic regression was used to examine univariate correlates of class
      membership, separately by gender. RESULTS: Participants were 75% male with a
      median age of 19 years. More than half of participants reported frequent alcohol
      use (>or=4 days/week) and half of the sample reported smoking MA >or=2 days/
      week. Three classes of activities emerged for male participants (n = 863): "work"
      (job related); "high-risk behaviors" (motorcycle riding, fighting, sex); and
      "combined" (all activities). Two classes emerged for the women (n = 299): "work"
      (housework) and "high-risk behaviors." "High-risk behaviors" and "combined" (men
      only) classes were associated with more frequent alcohol and methamphetamine use
      compared with the "work" class. CONCLUSIONS: Our study found a distinct typology
      of behaviors associated with substance abuse among young adults in Thailand.
      Behavioral typologies allow a better understanding of the nuances of "risky"
      behaviors and might prove useful in targeting interventions.

PMID- 19167667
TI  - Effects of integrating pedometers, parental materials, and E-mail support within
      an extracurricular school sport intervention.
AB  - PURPOSE: The objective of this study was to evaluate the impact of a school-based
      intervention (Program X) incorporating pedometers and e-mail support on physical
      activity, sedentary behavior, and healthy eating in adolescents. METHODS: A
      randomized control trial was used to evaluate the impact of the Program X
      intervention. Six schools (N = 124 participants; mean age 14.1 +/- .8 years) were
      randomized to intervention or control conditions for the 6-month study period.
      Objectively recorded physical activity (mean steps/day), self-reported sedentary
      behavior, and dietary habits were measured at baseline and at 6-month follow-up
      and intervention effects were assessed using repeated-measures analysis of
      variance and chi(2) tests. RESULTS: Participants in the intervention group
      increased their step counts by 956 +/- 4107 steps/day (boys) and 999 +/- 1999
      (girls). Repeated-measures analysis of variance revealed significant group-by
      time interactions for boys (F = 7.4, p = .01, d = .80) and girls (F = 29.6, p
      <.001, d = 1.27) for mean steps/day. The intervention significantly decreased the
      number of energy-dense/low-nutrient snacks consumed by boys (chi(2) = 4.0, p =
      .043) and increased the number of fruit serves among girls (chi(2) = 4.8, p =
      .028). The intervention did not have a statistically significant effect on
      sedentary behavior. CONCLUSION: A school-based intervention incorporating
      physical activity monitoring using pedometers and e-mail support was successful
      in promoting physical activity and selected healthy eating behaviors in
      adolescent boys and girls.

PMID- 19167668
TI  - Sexual behavior and desires among adolescents perinatally infected with human
      immunodeficiency virus in Uganda: implications for programming.
AB  - Counseling programs for adolescents living with human immunodeficiency virus
      (HIV) encourage abstinence from sex and relationships. This Uganda study,
      however, found that many of these adolescents are sexually active or desire to be
      in relationships but engage in poor preventive practices. Programs for HIV and
      acquired immunodeficiency syndrome (AIDS) programs therefore need to strengthen
      preventive services to this group.

PMID- 19167669
TI  - The quality of HIV testing services for adolescents in Cape Town, South Africa:
      do adolescent-friendly services make a difference?
AB  - We used adolescent simulated clients to evaluate whether HIV testing services in
      clinics participating in an adolescent-friendly initiative in Cape Town were
      superior to regular clinic services. We found improved accessibility to HIV
      testing, but no impact on adolescent's experience of negative attitudes from
      health workers and confidentiality breaches.

PMID- 19167670
TI  - Parents and health care professionals working together to improve adolescent
      health: the perspectives of parents.
AB  - One proposed strategy to improve adolescent health and health care is to create
      working partnerships among adolescent health care professionals (HCPs) and
      families. In this pilot qualitative study we interviewed 17 mothers to explore
      their perceptions of the role of parents, HCPs, and parent-HCP partnerships in
      addressing adolescent health issues.

PMID- 19167671
TI  - Population-based trends in male adolescent obesity in Israel 1967-2003.
AB  - Obesity increased monotonically from 1.2% to 3.8% of males age 17 (1967-2003).
      Low socioeconomic status had an independent positive effect on obesity. The
      likelihood of obesity had risen more steeply over time among the low
      socioeconomic status group than among other adolescents. Rise in obesity,
      standard of living, and income inequality (as measured by the Gini index)
      increased concomitantly.

PMID- 19167672
TI  - Abstracts of the SAM (Society of Adolescent Medicine) Annual Meeting. March 25
      26, 2009. Los Angeles, California, USA.

PMID- 19167674
TI  - Defining Medicare coverage for MDS treatment and research: a time for action?

PMID- 19167675
TI  - The role of cytotoxic therapy with hematopoietic stem cell transplantation in the
      therapy of myelodysplastic syndromes.

PMID- 19167676
TI  - The role of cytotoxic therapy with hematopoietic stem cell transplantation in the
      therapy of myelodysplastic syndromes: an evidence-based review.
AB  - Clinical research examining the role of hematopoietic stem cell transplantation
      (SCT) in the therapy of myelodysplastic syndromes (MDS) in adults is presented
      and critically evaluated in this systematic evidence-based review. Specific
      criteria were used for searching the published literature and for grading the
      quality and strength of the evidence and the strength of the treatment
      recommendations. Treatment recommendations based on the evidence are presented in
      Table 3, and were reached unanimously by a panel of MDS experts. The identified
      priority areas of needed future research in MDS include: (1) the benefit of using
      alternative donor sources (eg, cord blood; haploidentical family donors) for
      patients without matched sibling or unrelated donors; (2) the role and
      appropriate timing of allogeneic SCT in combination with hypomethylating and
      immunomodulatory treatment regimens; (3) randomized trials comparing the safety
      and efficacy of various novel agents for treating MDS; and (4) the influence of
      the various MDS treatment modalities on patient-reported quality-of-life
      outcomes.

PMID- 19167677
TI  - Rabbit anti T-lymphocyte globulin induces apoptosis in peripheral blood
      mononuclear cell compartments and leukemia cells, while hematopoetic stem cells
      are apoptosis resistant.
AB  - Polyclonal anti-T-lymphocyte globulins (ATG) are used in allogeneic stem cell
      transplantation (SCT) for the prophylaxis of graft versus host disease (GVHD) by
      in vivo T cell depletion. In this study we investigated the complement
      independent induction of apoptosis by rabbit ATG in peripheral blood mononuclear
      cell (PBMNC) compartments and hematopoetic stem cells (HSC). We also detected
      antileukemic activity of ATG by measuring apoptosis in myeloid and lymphatic
      leukemia cell lines and primary leukemia cells. We found ATG to induce apoptosis
      in T-lymphocytes (CD4(+), CD8+), B-lymphocytes (CD20+), natural killer (NK)-cells
      (CD56(+)), and monocytes (CD14(+)). HSC, in contrast, were apoptosis resistant
      and could be growth stimulated by low-dose ATG in the presence of bystander
      cells. The human leukemia cell lines Jurkat, Daudi, DG-75 (lymphoblastic), and
      K562, HL-60, KG1, and U937 (myeloblastic) underwent ATG-induced apoptosis,
      whereas the NK-cell line YT was resistant. Primary leukemia cells from 6
      investigated patients with acute lymphoblastic leukemia, 9 of 10 patients with
      chronic lymphocytic leukemia, and 4 of 8 patients with acute myeloblastic
      leukemia underwent ATG-induced apoptosis. We conclude apoptosis induction in all
      PBMNC compartments contributes to GVHD prophylaxis. ATG might support
      engraftment. Finally, antileukemic activity of ATG could positively influence the
      transplantation outcome.

PMID- 19167678
TI  - Activated notch supports development of cytokine producing NK cells which are
      hyporesponsive and fail to acquire NK cell effector functions.
AB  - Natural Killer (NK) cells are powerful effectors of cytotoxicity against
      "stressed" cells. They also produce cytokines and chemokines to activate the
      adaptive immune response. Understanding NK cell development and maturation may
      have implications for cancer therapy and for immunity against infections. We
      hypothesized that Notch signaling, critical for hematopoesis, would be involved
      in NK cell development. The role of constitutively activated Notch1 (ICN) on NK
      cell maturation was studied using human umbilical cord blood (UCB) progenitors
      cultured on a murine embryonic liver stroma cell line (EL08-1D2) and human
      cytokines. UCB CD34(+)/ICN(+) sorted cells resulted in a population of CD7(+)
      early lymphoid precursors and subsequent NK lineage commitment independent of
      stroma or IL-15. Early expression of L-selectin on ICN(+) precursors suggested
      their homing competence. These precursors further committed to the NK lineage,
      and were capable of producing cytokines and chemokines such as interleukin (IL)
      13, granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis
      factor-alpha (TNF-alpha), yet poorly acquired NK inhibitory receptors and
      cytotoxic effector function. In the presence of stroma, ICN(+) precursors also
      gave rise to a population of early T lineage committed cells characterized by
      expression of cytoplasmic CD3 gamma, epsilon, and delta chains, RAG1/2, and
      production of IL-2, suggesting bona fide Th1 commitment. Importantly, signals
      from EL08-1D2 stroma were required for this development process. In conclusion,
      sustained Notch signaling can replace stroma in differentiation of a common
      CD7(+) lymphoid precursor from UCB CD34(+) progenitors and induce NK cell
      commitment. However, these NK cells are immature in their cytokine production
      profile, are hyporesponsive, and poorly acquire NK cell receptors involved in
      self-tolerance and effector function.

PMID- 19167679
TI  - Influence of pretransplantation serum ferritin on nonrelapse mortality after
      myeloablative and nonmyeloablative allogeneic hematopoietic stem cell
      transplantation.
AB  - Iron overload might be an important contributor to nonrelapse mortality (NRM) in
      hematopoietic stem cell transplantation (HSCT). We studied 264 patients
      undergoing allogeneic HSCT for hematologic malignancies between 1996 and 2006,
      using pretransplantation serum ferritin as a surrogate marker of iron overload.
      At 5 years, patients in the high ferritin group (>or= 599 ng/mL) had a lower
      overall survival (OS; 33.0% versus 63.5%; P< .001) and a higher NRM (34.9% versus
      13.7%; P< .001) than those in the low ferritin group (<599 ng/mL). Multivariate
      analyses showed that high pretransplantation serum ferritin was a significant
      risk factor for worse survival (relative risk [RR]=1.68; P= .05) and increased
      NRM (RR=2.47; P= .01). There was no significant difference in the cumulative
      incidence of relapse, and acute and chronic graft-versus-host disease (aGVHD,
      cGVHD) between the 2 groups. Patients in the high ferritin group were more likely
      to die of infection (P< .010) and organ failure (P< .019). Similar results were
      observed after dividing the patients according to the intensity of conditioning
      regimens. These findings emphasize the prognostic impact of pretransplantation
      serum ferritin in HSCT recipients.

PMID- 19167680
TI  - IPSS poor-risk karyotype as a predictor of outcome for patients with
      myelodysplastic syndrome following myeloablative stem cell transplantation.
AB  - The optimal therapy for myelodysplastic syndrome (MDS) is allogeneic bone marrow
      (BM) or blood (BSC) stem cell transplantation (SCT), although outcomes are
      limited by nonrelapse mortality (NRM) and relapse. A retrospective review was
      performed of 156 patients who underwent SCT (114 BM, 42 BSC) for MDS or secondary
      acute myelogenous leukemia (sAML) at our institution. Fifty-five patients remain
      in continuous complete remission: 35 BM recipients and 20 BSC recipients (median
      follow-up 139 and 89 months, respectively). Estimated 7-year event-free survival
      (EFS), NRM, and risk of relapse (ROR) are 33% (95% confidence intervals [CI] 25%
      43%), 42% (CI 33%-51%), and 25% (CI 17%-33%) for the BM cohort and 45% (CI 32%
      64%, P= .07), 32% (CI 18%-47%, P= .15), and 23% (CI 11%-37%, P= .79) for the BSC
      cohort. Multivariate analysis showed IPSS poor-risk cytogenetics (P< .001), time
      from diagnosis to SCT (P< .001), FAB subgroup (P= .001), recipients not in
      complete remission (CR1) at SCT (P= .005), and the development of acute graft
      versus-host disease (aGVHD) (P= .04) were all predictive of an inferior EFS. The
      FAB subgroup (P= .002), poor-risk karyotype (P= .004), and non-CR1 status also
      correlated with ROR in multivariate analysis. EFS for poor-risk karyotype
      patients was superior after receiving BSC compared to BM (39% versus 6%, P<
      .001). SCT outcomes in MDS/sAML are strongly associated with the IPSS cytogenetic
      risk group, although the use of BSC in poor-risk karyotype patients may lead to a
      more favorable long-term EFS.

PMID- 19167681
TI  - Promising progression-free survival for patients low and intermediate grade
      lymphoid malignancies after nonmyeloablative umbilical cord blood
      transplantation.
AB  - Nonmyeloablative hematopoietic cell transplantation (HCT) has been used to treat
      patients with advanced or high-risk lymphoid malignancies. We studied 65 patients
      (median age 46 years) receiving an umbilical cord blood (UCB) graft after a
      single conditioning regimen consisting of cyclophosphamide (50 mg/kg) on day -6,
      fludarabine (40 mg/m(2)) daily on days -6 to -2, as well as a single fraction of
      total-body irradiation (TBI) (200 cGy) along with cyclosporine mycophenolate
      mofetil immunosuppression. Median time to neutrophil and platelet recovery was
      7.5 days (range: 0-32) and 46 days (range: 8-111), respectively. Cumulative
      incidences of grade II-IV, grade III-IV acute, and chronic graft-versus-host
      disease (aGVHD, cGVHD) were 57% (95% confidence interval [CI]: 43%-70%), 25% (95%
      CI: 14%-35%), and 19% (95% CI: 9%-29%), respectively. Transplant-related
      mortality at 3 years was 15% (95% CI: 5%-26%). Median follow-up was 23 months.
      The progression free-survival (PFS), current PFS and overall survival (OS) were
      34% (95% CI: 21%-47%), 49% (95% CI: 36%-62%), and 55% (95% CI: 42%-70%) at 3
      years. Based on our data, we conclude that a nonmyeloablative conditioning
      regimen followed by UCB transplantation is an effective treatment for patients
      with advanced lymphoid malignancies who lack a suitable sibling donor.

PMID- 19167682
TI  - Assessment of the hematopoietic cell transplantation comorbidity index in non
      Hodgkin lymphoma patients receiving reduced-intensity allogeneic hematopoietic
      stem cell transplantation.
AB  - The hematopoietic cell transplantation comorbidity index (HCT-CI), a weighted
      index of 17 pretransplantation comorbidities, has been validated in
      nonmyeloablative and myeloablative allogeneic hematopoietic stem cell
      transplantation (HSCT) studies, but it has not been specifically tested in
      patients with non-Hodgkin lymphoma (NHL) receiving reduced-intensity conditioning
      (RIC). We performed a retrospective analysis to assess the impact of the HCT-CI
      on outcomes of NHL patients treated with HSCT relative to treatment-related
      mortality (TRM), disease-related mortality (DRM), with a specific emphasis on
      overall survival (OS). Individual pretransplantation and disease-related factors
      also were analyzed with HCT-CI relative to their impact on OS. All patients were
      uniformly treated with an identical pretransplantation induction regimen and an
      identical RIC regimen (cyclophosphamide [Cy]/fludarabine [Flu]), and received T
      cell-replete allografts from HLA-matched siblings. The analysis included 63 NHL
      patients with a median HCT-CI score of 2 (range, 0 to 11). The HCT-CI (0 to 2
      comorbidities vs 3+ comorbidities) demonstrated a potential association with TRM,
      but not with DRM, at 100 days (4.5% vs 26.3%) and at 1 year (13.6% vs 36.8%)
      posttransplantation. The factor most strongly associated with OS was response to
      pretransplantation chemotherapy (P= .0001), based on a composite measure. In a
      Cox model, pretransplantation chemotherapy response remained the most important
      factor (P< .0001) relative to OS, and there was a trend (P= .056) toward HCT-CI
      adding predictive value for OS. Although HCT-CI may be useful for predicting TRM,
      our data further underscore the importance of response to chemotherapy before
      transplantation as a predictor of overall transplantation outcome in NHL patients
      being considered for RIC allogeneic HSCT.

PMID- 19167683
TI  - Association between busulfan exposure and outcome in children receiving
      intravenous busulfan before hematologic stem cell transplantation.
AB  - Busulfan, combined with therapeutic drug monitoring-guided dosing, is associated
      with higher event-free survival (EFS) rates due to fewer graft failures/relapses
      and lower toxicity. The optimal target area under the curve (AUC) and dosing
      schedule of intravenous busulfan in children undergoing hematopoietic stem cell
      transplantation (HSCT) remain unclear, however. We conducted a retrospective
      analysis of the association between busulfan exposure and clinical outcome in 102
      children age 0.2 to 21 years who received busulfan 1 or 4 times daily before
      undergoing HSCT (46 malignant and 56 nonmalignant indications). EFS and overall
      survival after a median of 2 years of follow-up were 68% and 72%, respectively.
      EFS was optimal when the exposure of busulfan (AUC) was 78 mg x h/L (95%
      confidence interval=74 to 82 mg x h/L). Acute graft-versus-host disease (aGVHD)
      grade II-IV occurred more frequently with greater busulfan exposure. The addition
      of melphalan was an independent risk factor; melphalan use combined with high
      busulfan exposure (AUC >74 mg x h/L) was associated with high incidences of aGVHD
      (58%), veno-occlusive disease (66%), and mucositis grade III-IV (26%). Dosing
      frequency (1 or 4 times daily) was not related to any outcome. In conclusion,
      dose targeting of busulfan to a narrow therapeutic range was found to increase
      EFS in children. Adding melphalan to optimal busulfan exposure is associated with
      a high incidence of toxicity.

PMID- 19167684
TI  - Phase II study of risk-adapted therapy of newly diagnosed, aggressive non-Hodgkin
      lymphoma based on midtreatment FDG-PET scanning.
AB  - In newly diagnosed aggressive non-Hodgkin lymphoma (NHL), a positive midtreatment
      fluorine-18 fluorodeoxyglucose positron emission tomography (PET) scan often
      carries a poor prognosis, with reported 2-year event-free survival (EFS) rates of
      0% to 30% after standard therapy. To determine the outcome of early treatment
      intensification for midtreatment PET-positive disease, a phase II trial of risk
      adapted therapy was conducted. Fifty-nine newly diagnosed patients, 98% with B
      cell lymphoma, had PET/CT performed after 2 or 3 cycles of first-line
      chemotherapy. Those with negative PET on semiquantitative visual interpretation
      completed standard therapy. Those with positive PET received platinum-based
      salvage chemotherapy, high-dose therapy, and autologous stem cell transplantation
      (ASCT). Midtreatment PET was positive in 33 (56%); 28 received ASCT with an
      actuarial 2-year EFS of 75% (95% confidence interval, 60%-93%). On intention-to
      treat analysis, 2-year EFS was 67% (53%-86%) in all PET-positive patients and 89%
      (77%-100%) in PET-negative patients. No association was found between the
      International Prognostic Index category and the midtreatment PET result. The
      favorable outcome achieved here in historically poor-risk patients warrants
      further, more definitive investigation of treatment modification based on early
      PET scanning.

PMID- 19167685
TI  - Treatment with plerixafor in non-Hodgkin's lymphoma and multiple myeloma patients
      to increase the number of peripheral blood stem cells when given a mobilizing
      regimen of G-CSF: implications for the heavily pretreated patient.
AB  - We investigated the efficacy and toxicity of combining granulocyte-colony
      stimulating factor (G-CSF) at standard doses with plerixafor, a CXCR4 inhibitor,
      to mobilize stem cells in patients with non-Hodgkin's lymphoma (NHL) and multiple
      myeloma (MM). Patients with NHL and MM underwent mobilization with G-CSF (10
      microg/kg/day) for up to 9 days and plerixafor (240 microg/kg/day), which started
      on the evening of day 4. Apheresis began on day 5 and continued daily until
      either >or= 5 x 10(6) CD34/kg were collected or to a maximum of 5 aphereses.
      Toxicities, increase in circulating CD34 cells/microL before and after the first
      dose of plerixafor, percentage of patients collecting >or= 5 x 10(6) CD34/kg,
      total CD34 cells/kg collected, engraftment, and exploratory efficacy analyses in
      heavily pretreated patients were examined. Six sites enrolled 49 patients (NHL,
      23; MM, 26). All completed mobilization and 47 of 49 (96%) underwent transplant.
      Circulating CD34 cells/microL increased by 2.5-fold (1.3-6.0-fold) after the
      first plerixafor dose. The median CD34 cells/kg collected was 5.9 x 10(6) (1.5
      22.5) in 2 (1-5) days of aphereses. Median days to neutrophil and platelet
      engraftment were 11 (8-16) and 14.5 (7-39) days, respectively. Adverse events
      primarily were mild nausea and diarrhea (n=24). Twenty-eight (57%) were
      identified as heavily pretreated patients. Their median fold increase in
      circulating CD34 cells/microL was 2.5 (1.4-5.0) after plerixafor, similar to
      minimally pretreated patients. Plerixafor and G-CSF increased circulating CD34
      cells/microL and led to the adequate collection of stem cells for autotransplant
      in 96% of the patients. This combination may have particular value in heavily
      pretreated patients.

PMID- 19167686
TI  - Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical
      blood and bone marrow transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the
      best therapeutic options to cure acute leukemia (AL). However, many patients have
      no human leukocyte antigen (HLA)-matched donor. Recently, we developed a new
      method for HLA-mismatched/haploidentical transplantation without in vitro T cell
      depletion (TCD). This method combined granulocyte-colony stimulating factor (G
      CSF)-primed bone marrow and peripheral blood with intensive immunosuppression. We
      analyzed the outcome of 250 consecutive patients with AL who underwent HLA
      mismatched/haploidentical transplantation with 1-3 mismatched loci of HLA-A, B,
      and DR from family donors via our new transplant protocol. Two hundred forty-nine
      patients achieved sustained, full donor chimerism. The incidence of grade 2-4
      acute graft-versus-host disease (aGVHD) was 45.8%, and that of grades 3 and 4 was
      13.4%, which was not associated with the extent of HLA disparity. The cumulative
      incidence of total chronic GVHD (cGVHD) was 53.9% and that of extensive cGVHD was
      22.6% in 217 evaluable patients. One hundred forty-one of the 250 patients
      survived free of disease recurrence at a median of 1092 days (range: 442-2437
      days) of follow-up. Seventeen patients received DLI as a treatment for relapse
      after transplantation and 7 patients achieved leukemia-free survival (LFS). The 3
      year probability of LFS for acute myelogenous leukemia (AML) was 70.7% and 55.9%,
      and for acute lymphoblastic leukemia (ALL) it was 59.7% and 24.8% in standard
      risk and high-risk groups, respectively. Lower LFS were associated with diagnosis
      of acute leukemia in the high-risk group (P= .001, relative risk [RR], 95%
      confidence interval [CI]: 2.94[1.535-5.631]) and the occurrence of aGVHD of
      grades 3 and 4 (P= .004). HLA-mismatched/haploidentical HSCT was feasible with
      unmanipulated blood and bone marrow harvest.

PMID- 19167687
TI  - Role of antithymocyte globulin and granulocyte-colony stimulating factor
      mobilized bone marrow in allogeneic transplantation for patients with hematologic
      malignancies.
AB  - The main obstacle for allogeneic transplantation is delayed hematologic
      reconstitution and serious graft-versus-host disease (GVHD). The results of 128
      patients with hematologic malignancies undergoing HLA-identical (n=52) or HLA
      haploidentical/mismatched (n=76) hematopoietic stem cell transplantation (HSCT)
      performed during the same time period were compared. Patients with HLA-identical
      HSCT received unmanipulated granulocyte-colony stimulating factor-mobilized
      peripheral blood stem cells (G-PBSCs). Forty-six patients with HLA-haploidentical
      related HSCT received antithymocyte globulin (ATG) in conditioning regimens
      followed by the transplantation of the combination of unmanipulated G-PBSCs and
      granulocyte-colony stimulating factor-mobilized bone marrow (G-BM) and 30
      patients with HLA-mismatched unrelated HSCT received ATG in conditioning regimens
      followed by the transplantation of unmanipulated G-PBSCs. All patients got
      successful hematopoietic engraftment. The cumulative incidences of grades I to II
      acute GVHD (aGVHD) on day 100 in the identical, haploidentical related and
      mismatched unrelated cohorts were 21.2%, 43.5%, and 53.3%, respectively. The
      cumulative incidences of chronic GVHD (cGVHD) in the identical, mismatched
      unrelated, and haploidentical related cohorts were 34.6%, 33.3%, and 10.9%,
      respectively. The 2-year relapse and treatment-related mortality (TRM) rates were
      19.2%, 23.9%, 23.3%, and 9.6%, 8.7%, 10% for patients who underwent identical,
      HLA-haploidentical related, and mismatched unrelated transplantation,
      respectively. The 2-year probabilities of leukemia-free survival and overall
      survival were 72.2%, 70.6%, 68.1%, and 76.5%, 77.8%, 70.0% after identical,
      haploidentical related and mismatched unrelated transplantations, respectively.
      Multivariate analyses showed that only advanced disease stage and a diagnosis of
      disease had increased risk of relapse, treatment failure, and overall mortality.
      In conclusion, it is a feasible approach with acceptable outcomes for patients
      undergoing HLA-haploidentical related HSCT by the combination of G-PBSCs and G-BM
      with conditioning regimens including ATG.

PMID- 19167688
TI  - Total and active rabbit antithymocyte globulin (rATG;Thymoglobulin)
      pharmacokinetics in pediatric patients undergoing unrelated donor bone marrow
      transplantation.
AB  - Rabbit antithymocyte globulin (rATG; Thymoglobulin) is currently used to prevent
      or treat graft-versus-host disease (GVHD) during hematopoietic stem cell
      transplantation (HSCT). The dose and schedule of rATG as part of the preparative
      regimen for unrelated donor (URD) bone marrow transplantation (BMT) have not been
      optimized in pediatric patients. We conducted a prospective study of 13 pediatric
      patients with hematologic malignancies undergoing URD BMT at St. Jude Children's
      Research Hospital from October 2003 to March 2005, to determine the
      pharmacokinetics and toxicities of active and total rATG. The conditioning
      regimen comprised total body irradiation (TBI), thiotepa, and cyclophosphamide
      (Cy); cyclosporine (CsA) and methotrexate (MTX) were administered as GVHD
      prophylaxis. Patients received a total dose of 10 mg/kg rATG, and serial blood
      samples were assayed for total rATG by enzyme linked immunosorbent assay (ELISA)
      and active rATG by florescein activated cell sorting (FACS). We found that our
      weight-based dosing regimen for rATG was effective and well tolerated by
      patients. The half-lives of total and active rATG were comparable to those from
      previous studies, and despite high doses our patients had low maximum
      concentrations of active and total rATG. There were no occurrences of grade iii
      iv GVHD even in patients having low peak rATG levels, and the overall incidence
      of grade II GVHD was only 15%. None of the patients had serious infections
      following transplantation. These data support the use of a 10 mg/kg dose of rATG
      in children with hematologic malignancies because it can be administered without
      increasing the risk of graft rejection, or serious infection in pediatric
      patients with a low rate of GVHD. These conclusions may not apply to patients
      with nonmalignant disorders.

PMID- 19167689
TI  - Ian Fraser Kerr Muir: a gentle giant of plastic surgery.

PMID- 19167690
TI  - Stress state mediation between environmental variables and performance: the case
      of noise and vigilance.
AB  - Effects of environmental variables on performance may be mediated by individual
      stress states. In this study the effects of jet-aircraft engine noise and signal
      salience on vigilance performance and self-reported stress state were examined.
      One hundred and ninety-two (96 female and 96 male) participants were randomly
      assigned to four experimental conditions consisting of 48 participants each
      resulting from the factorial combination of signal salience (high and low
      salience signals) and noise (95 dBA intermittent aircraft noise or quiet).
      Performance metrics and self-reported stress state (Task Engagement, Distress,
      and Worry) were collected. Performance in the noise conditions was significantly
      better than in the quiet conditions. Performance in the high salience conditions
      was significantly better than the low salience conditions. Noise elevated Task
      Engagement and low signal salience elevated Distress. Moreover, structural
      equation model analyses were used to examine stress state mediation between the
      experimental variables and performance. These analyses indicated Engagement
      mediates between noise and vigilance performance.

PMID- 19167691
TI  - Elevated body mass index and use of coronary revascularization after cardiac
      catheterization.
AB  - BACKGROUND: Obese persons suffer discrimination in society that may extend to
      health care use. We investigated whether overweight and obese patients are as
      likely to undergo coronary reperfusion or revascularization as patients of normal
      body weight. METHODS: Detailed clinical data were collected for an inception
      cohort of patients from Alberta, Canada, who underwent cardiac catheterization
      between April 2001 and March 2004. The patients' likelihood of receiving any
      revascularization, percutaneous coronary intervention, or coronary artery bypass
      graft surgery in the year after cardiac catheterization was examined on the basis
      of body mass index (BMI) grouping. Use of revascularization was examined
      separately for patients with high- and low-risk coronary disease. RESULTS: Of
      27,460 patients who had BMI data recorded, 24% were of normal weight, 42% were
      overweight, and 35% were obese. Although overweight and obese patients were more
      likely to have percutaneous coronary intervention (adjusted hazard ratio
      [HR]=1.07, 95% confidence interval [CI], 1.01-1.12 and HR 1.08, 95% CI, 1.01
      1.13, respectively), obese patients (BMI>30) were less likely to receive coronary
      artery bypass graft surgery (adjusted HR=0.93, 95% CI, 0.87-1.00). This was
      primarily because of less use of coronary artery bypass graft surgery for the
      most obese patients (obesity class III) with low-risk coronary anatomy (adjusted
      HR=0.61, 95% CI, 0.36-1.02). CONCLUSION: The pattern of use of revascularization
      procedures after cardiac catheterization differs somewhat across BMI subgroups.
      These differences might be clinically appropriate, but they warrant further
      exploration.

PMID- 19167692
TI  - Biochemical tissue-specific injury markers of the heart and brain in postpartum
      cord blood.
AB  - OBJECTIVE: We sought to establish references ranges and to test the hypothesis
      that biochemical tissue-specific markers for the heart in umbilical cord blood of
      newborns with cardiac defects and intrauterine growth restriction (IUGR) are
      abnormal. STUDY DESIGN: A prospective study was conducted. Serum samples of the
      umbilical vein (n = 280) and artery (n = 156) from 599 healthy newborns at 37(+0)
      42(+0) weeks of gestation were collected. Total creatine kinase (CK), CK-MB heart
      type (CK-MB), cardiac troponin T (cTnT), myoglobin, N-terminal pro-B-type
      natriuretic peptide (NT-proBNP), and S100 were measured. Reference ranges for
      each marker were constructed. Concentrations of tissue-specific markers from
      umbilical cord blood of neonates with cardiac defects (n = 10) and IUGR (n = 41)
      were plotted against the established reference ranges. RESULTS: Reference ranges
      for each studied marker were established for both umbilical artery and vein. In
      fetuses with cardiac defects, both NT-proBNP (4/6 [66%] in the artery, 7/10 [70%]
      in the vein) and cTnT (2/10 [20%] in the vein) were increased. In fetuses with
      IUGR in the vein, NT-proBNP (10/41 [24%]) and cTnT (5/41 [12%]) were increased,
      whereas S100 (9/41 [21%]) was decreased. CONCLUSION: In a subset of neonates with
      cardiac defects or growth restriction, irrespective of the pH at birth, tissue
      specific injury markers for the heart in umbilical cord blood are abnormal.

PMID- 19167693
TI  - Desvenlafaxine for the treatment of vasomotor symptoms associated with menopause:
      a double-blind, randomized, placebo-controlled trial of efficacy and safety.
AB  - OBJECTIVE: The objective of the study was to assess the efficacy and safety of
      desvenlafaxine (administered as desvenlafaxine succinate) for the treatment of
      vasomotor symptoms. STUDY DESIGN: This was a 26 week, double-blind, placebo
      controlled trial of 567 postmenopausal women (mean age, 53.7 years; time since
      natural menopause, 4.8 years) experiencing 50 or more hot flushes (HFs) per week,
      randomly assigned to desvenlafaxine (100 or 150 mg) or placebo. Change from
      baseline in average daily number of moderate to severe HFs and average daily HF
      severity were compared with placebo at weeks 4, 12, and 26. RESULTS: A
      significantly greater decrease from baseline in number of HFs occurred at weeks 4
      and 12 with 100 and 150 mg desvenlafaxine compared with placebo (week 12
      reductions: 60%, 66%, and 47%, respectively; all P < or = .002). Only the 150 mg
      dose showed significant improvement from baseline at 26 weeks compared with
      placebo (week 26 reductions: 61%, 69%, and 51%, respectively), although the study
      was not powered to demonstrate efficacy beyond the initial 12 weeks of therapy.
      The average daily severity decreased significantly more at weeks 4 and 12 with
      desvenlafaxine compared with placebo (all P < or = .002). Significantly more
      desvenlafaxine-treated subjects than placebo-treated subjects discontinued
      because of adverse events during week 1 only. CONCLUSION: Desvenlafaxine is an
      effective treatment for menopausal HFs.

PMID- 19167694
TI  - Effect of gestational age at the prior cesarean delivery on maternal morbidity in
      subsequent VBAC attempt.
AB  - OBJECTIVE: The purpose of this study was to estimate the effect of gestational
      age at the time of prior cesarean on maternal morbidity in women attempting
      vaginal birth after cesarean delivery (VBAC). STUDY DESIGN: A retrospective
      cohort study of women attempting VBAC, comparing women with a prior cesarean
      delivery < or = 34 completed weeks to women with a prior cesarean delivery > 34
      weeks. The primary outcome was maternal morbidity, including uterine rupture.
      Univariable, stratified, and multivariable analyses were used to estimate the
      effect of a prior cesarean performed at < or = 34 weeks on maternal morbidities.
      RESULTS: Of 19,474 women with 1 prior cesarean, 12,535 attempted VBAC and 508 of
      those had a previous cesarean < or = 34 weeks. Study groups had similar risks of
      uterine rupture (adjusted OR [AOR], 1.5; 95% CI, 0.7-3.5; P = .32) and composite
      morbidity (AOR, 0.9; 95% CI, 0.5-1.8; P = .81). CONCLUSION: Prior cesarean
      delivery at < or = 34 weeks' gestation does not appear to increase the risk of
      maternal morbidity in a subsequent VBAC attempt.

PMID- 19167695
TI  - Medium-term comparison of continence rates after rectus fascia or midurethral
      sling placement.
AB  - OBJECTIVE: The purpose of this study was to compare continence rates after
      placement of rectus fascia or midurethral slings. STUDY DESIGN: We performed a
      retrospective cohort study of 242 women who underwent rectus fascia (n = 79) or
      midurethral (n = 163) sling procedures to treat urinary incontinence. Outcome was
      based on responses to validated questionnaires and need for interim treatment for
      incontinence. Survival free of incontinence was estimated using the Kaplan-Meier
      method. Associations between patient factors and survival free of incontinence
      were evaluated by fitting Cox proportional hazards models. RESULTS: Women with
      rectus fascia slings were more likely to report any leakage of urine (P = .04)
      and were 13 times more likely to require urethrolysis (P < .001) than patients
      with midurethral slings. Patient satisfaction was lower in the rectus fascia
      sling group compared with the midurethral sling group (P = .01). CONCLUSION:
      Midurethral slings appear to be more effective than rectus fascia slings and are
      less likely to cause postoperative voiding complications.

PMID- 19167696
TI  - Placement of a transvaginal bone-anchored sling A new minimally invasive
      technique is useful in stress urinary incontinence.

PMID- 19167697
TI  - Posttreatment human papillomavirus testing for recurrent cervical intraepithelial
      neoplasia: a systematic review.
AB  - OBJECTIVE: We conducted a systematic review to evaluate the characteristics of
      human papillomavirus testing, particularly Hybrid Capture 2, in follow-up
      evaluations after treatment for cervical intraepithelial neoplasia for the
      detection of residual or recurrent cervical intraepithelial neoplasia grade >/=
      2. STUDY DESIGN: Medline was searched for relevant studies that were published
      between 1992 and September 2007. Of the 1107 citations that were identified, 20
      articles met the inclusion criteria. RESULTS: Studies that used polymerase chain
      reaction testing were too heterogeneous to combine. We identified 5 studies that
      performed both Hybrid Capture 2 and colposcopy. Pooled sensitivity for Hybrid
      Capture 2 was 90.7% (95% CI, 75.4-96.9%), and pooled specificity was 74.6% (95%
      CI, 60.4-85.0%). Pooled sensitivity for cervical cytologic testing was 76.6% (95%
      CI, 62.0-86.8%), and pooled specificity was 89.7% (95% CI, 22.7-99.6%).
      CONCLUSION: Hybrid Capture 2 testing can identify approximately 91% of women with
      residual or recurrent cervical intraepithelial neoplasia grade >/= 2; however,
      approximately 30% of women would undergo colposcopy in follow-up evaluation.

PMID- 19167698
TI  - Laparoscopic surgery vs laparotomy for early stage endometrial cancer: long-term
      data of a randomized controlled trial.
AB  - OBJECTIVE: The purpose of the study was to compare the long-term safety and
      efficacy of laparoscopic surgery and laparotomy approaches to early stage
      endometrial cancer. STUDY DESIGN: This was a prospective long-term extension
      study of a randomized controlled study that included 84 patients with clinical
      stage I endometrial cancer (laparoscopic surgery group, 40 women; laparotomy
      group, 38 women). Safety and efficacy data were evaluated and analyzed by the
      intention-to-treat principle. RESULTS: After a follow-up period of 78 months
      (interquartile range, 7; range, 19-84 months) and 79 months (interquartile range,
      6; range, 22-84 months) for laparoscopic surgery and laparotomy groups,
      respectively, no difference in the cumulative recurrence rates (8/40 [20.0%] and
      7/38 [18.4%]; P = .860) and deaths (7/40 [17.5%] and 6/38 [15.8%] patients; P =
      .839) was detected between groups. No significant differences in overall (P =
      .535) and disease-free (P = .512) survival were observed. CONCLUSION: The
      laparoscopic surgery approach to early stage endometrial cancer is as safe and
      effective a procedure as the laparotomy approach.

PMID- 19167699
TI  - Clinical follow-up of women infected with human papillomavirus-16, either alone
      or with other human papillomavirus types: identification of different risk
      groups.
AB  - OBJECTIVES: Evaluation of the clinical impact of multiple infections of the
      cervix by human papillomavirus, including human papillomavirus-16, compared with
      single human papillomavirus-16 infection. STUDY DESIGN: One hundred sixty-nine
      women were classified in 3 categories depending on their human papillomavirus
      profile: human papillomavirus-16 only, human papillomavirus-16 and low-risk
      type(s), and human papillomavirus-16 and other high-risk type(s). Cervical brush
      samples were analyzed for human papillomavirus DNA by polymerase chain reaction
      and reverse line blot hybridization. All women were evaluated with colposcopy
      during 24 months or more. Management was according to the Bethesda
      recommendations. RESULTS: Women infected with human papillomavirus-16 and other
      high-risk human papillomavirus type(s) presented more progression or no change in
      the grade of dysplasia, compared with women of the other groups (relative risk
      [RR], 1.39; 95% confidence interval [CI], 1.07-1.82; P = .02 at 6 months; RR,
      2.10; 95% CI, 1.46-3.02; P < .001 at 12 months; RR, 1.82; 95% CI, 1.21-2.72; P =
      .004 at 24 months). CONCLUSION: Coinfection of women with human papillomavirus-16
      and other high-risk human papillomavirus type(s) increases the risk of
      unfavorable evolution.

PMID- 19167700
TI  - Changes in gyrification over 4 years in bipolar disorder and their association
      with the brain-derived neurotrophic factor valine(66) methionine variant.
AB  - BACKGROUND: Evidence suggests that structural brain changes occur over time in
      bipolar disorder but few studies have examined this longitudinally. Additional
      work implicates brain-derived neurotrophic factor (BDNF) valine
      (val)(66)methionine (met) variant in these changes. The present study examined
      longitudinal trends in prefrontal gyrification index (GI) in bipolar disorder and
      the effect of BDNF genotype. METHODS: Eighteen patients with bipolar I disorder
      and 18 control subjects underwent magnetic resonance imaging at study entry and
      after 4 years. Prefrontal GI was computed as the ratio of folded inner contour to
      exposed outer contour. RESULTS: Ventral and dorsal GI decreased significantly
      with time in both cohorts; the rate did not differ for bipolar patients. Within
      the bipolar cohort, individuals with one or more BDNF met alleles showed greater
      losses in GI, an effect that correlated with gray matter loss in the left
      hemisphere. CONCLUSIONS: Gyrification index may be sensitive to atrophy, as well
      as being a neurodevelopmental measure. While the loss of prefrontal gyrification
      over time is not accelerated in bipolar disorder, a greater rate of loss is
      associated with the possession of one or more BDNF met alleles.

PMID- 19167701
TI  - Baseline and amphetamine-stimulated dopamine activity are related in drug-naive
      schizophrenic subjects.
AB  - BACKGROUND: Previous studies demonstrated increased striatal dopamine (DA)
      release after amphetamine challenge and increased striatal baseline occupancy of
      D2 receptors in patients with schizophrenia compared with control subjects. We
      report here on the relationship between these two aspects of DA release in drug
      naive patients with schizophrenia (SCZ) and matched healthy control subjects
      (HC). METHODS: Six drug-naive SCZ and eight HC underwent single-photon emission
      computed tomography (SPECT) scans after bolus followed by constant infusion of
      (S)-(-)-3-[123I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2
      pyrrolidinyl)methyl]benzamide ([123I]IBZM) under three conditions to determine
      the equilibrium specific to non-displaceable binding potential (BP(ND)) for
      striatal D2 at baseline, after amphetamine administration and after DA depletion.
      RESULTS: Amphetamine induced decrease in BP(ND) was positively correlated with
      BP(ND) increase after DA depletion in SCZ (p = .02) but not in HC (p = .44).
      Additionally, both were significantly increased. CONCLUSIONS: In drug-naive
      patients with schizophrenia but not in control subjects, stimulated and baseline
      DA release are both increased and positively correlated. At the neuronal level
      this association suggests that capacity for storage in presynaptic terminals,
      measured with the amphetamine paradigm, and baseline intrasynaptic DA release,
      measured with the alpha-methyl-para-tyrosine (alpha MPT) paradigm, are associated
      in schizophrenia, both consistent with increased midbrain DA cells activity.

PMID- 19167703
TI  - Involvement of thyroid hormones in the alterations of T-cell immunity and tumor
      progression induced by chronic stress.
AB  - BACKGROUND: Stress alters the neuroendocrine system, immunity, and cancer.
      Although the classic stress hormones are glucocorticoids and catecholamines,
      thyroid hormones have also been related to stress. We recently reported that
      chronic restraint stress impairs T-cell mediated immunity and enhances tumor
      growth in mice. METHODS: To study the participation of these hormones on the
      stress-induced alterations of the immune function and lymphoma growth, mice were
      subjected to acute or chronic stress, with or without thyroxin supplementation.
      Hormone levels, immune status, and cancer progression were evaluated. RESULTS:
      Differential endocrine alterations were observed in response to acute and chronic
      stress. Although corticosterone and noradrenaline levels were increased by acute
      stress, they were restored after prolonged exposure to the stressor. Instead,
      thyroid hormone levels were only reduced in chronically stressed animals in
      comparison with control subjects. Correlating, chronic but not acute stress
      impaired T-cell reactivity. Thyroxin replacement treatment of chronic restraint
      stress-exposed mice, which restored the euthyroid status, reversed the observed
      reduction of T-cell lymphoproliferative responses. Moreover, therapeutic thyroid
      replacement also reversed the alterations of lymphoma growth induced by chronic
      stress in syngeneic mice bearing tumors as well as Interleukin-2 production and
      specific cytotoxic response against tumor cells. Finally, we found that the
      isoforms theta and alpha of the protein kinase C are involved in these events.
      CONCLUSIONS: These results show for the first time that thyroid hormones are
      important neuroendocrine regulators of tumor evolution, most probably acting
      through the modulation of T-cell mediated immunity affected by chronic stress.

PMID- 19167702
TI  - Long-lasting incubation of conditioned fear in rats.
AB  - BACKGROUND: In 1937, Diven reported that human fear responses to cues previously
      paired with shock progressively increase or incubate over 24 hours. Since then,
      fear incubation has been demonstrated in both humans and nonhumans. However, the
      difficulty of demonstrating long-lasting fear incubation in rodents has hampered
      the study of the underlying mechanisms of this incubation. Here, we describe a
      rat procedure where fear reliably incubates over time. METHODS: We trained food
      restricted rats to lever-press for food pellets in daily 90-min sessions. We then
      gave each rat 100 30-sec tones co-terminating with a .5-sec .5-mA footshock over
      10 days (10 pairings/day). Groups of rats (n = 10-15) were then given four
      presentations of the tone (the fear cue) 2, 15, 31, or 61 days after fear
      conditioning training and were assessed for conditioned suppression of lever
      pressing. RESULTS: We found that conditioned fear responses were significantly
      higher 31 and 61 days after fear training than after 2 or 15 days. In control
      experiments, we showed that extensive tone-shock pairing is necessary for the
      emergence of fear incubation and that it is unlikely that non-associative factors
      contribute to this incubation. CONCLUSIONS: We describe a procedure for
      generating reliable and long-lasting conditioned fear incubation. Our procedure
      can be used to study mechanisms of fear incubation and might provide a model for
      studying the mechanisms of delayed-onset posttraumatic stress disorder that occur
      in a sub-population of people previously exposed to chronic stressors.

PMID- 19167704
TI  - STON: A novel method for protein three-dimensional structure comparison.
AB  - Protein structure comparison is an important problem in bioinformatics and has
      many applications in the study of structural and functional genomics. During the
      last decades, various heuristic methods have been developed to solve the protein
      structure comparison problem. Most of the protein structure comparison methods
      give the alignment based on the minimum RMSD (root mean square deviation) and
      ignore many significant local alignments that may be important for evolutional or
      functional studies. We have developed a new algorithm to find aligned residues in
      two proteins with desired RMSD value. The parameterized distance and rotation in
      this program enable us to search for strongly or weakly similar aligned fragments
      in two proteins.

PMID- 19167705
TI  - WITHDRAWN: Protection of cryopreserved human dermis by glycerol, sucrose and
      trehalose against gamma irradiation damage.
AB  - This article has been withdrawn at the request of the author. 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- 19167707
TI  - Trends in preschool lead exposure, mental retardation, and scholastic
      achievement: association or causation?
AB  - This study shows that 1936-1990 preschool blood lead trends explain 65% of the
      1948-2001 variation in USA mental retardation (MR) prevalence, 45% of the 1953
      2003 variation in the average scholastic achievement test (SAT) verbal score, and
      65% of the 1953-2003 variation in the average SAT math score. These temporal
      relationships are characterized by best-fit time lags (highest R(2) and t-value
      for blood lead) consistent with lead-induced cognitive damage in the first year
      of life: a 12-year lag for school-age MR, and a 17-year lag for SAT scores.
      Recent shifts in age-specific MR prevalence are consistent with recent trends in
      preschool blood lead. SAT and MR trends by race are consistent with racial
      differences in how 1960s slum clearance affected childhood exposure to severe
      lead paint hazards. SAT trends by Hispanic origin are consistent with an
      especially sharp fall in preschool blood lead in New York City since 1970.

PMID- 19167708
TI  - Dermatoglyphic changes during the population admixture between Kam and Han
      Chinese.
AB  - Genetic studies and gene localization for human dermatoglyphs are currently
      ongoing. However, the inheritance modes of various genetic traits are not well
      understood because of the complexity of dermatoglyph genetics. The study of
      admixed populations can contribute to the understanding of population genetic
      traits of dermatoglyphs. Here, we present the dermatoglyphic characteristics of
      Kam and Liujia Han, and the admixed population consisting of these two parent
      populations. The characteristics of the admixed population do not always fall in
      the same ranges as the parent population characters but do seem to be biased to
      Kam or Liujia parent populations, depending on sex and ethnicity of parents. The
      total frequencies of different fingerprint types do not differ among these
      populations, but several of the quantitative traits and the palm true pattern
      frequencies do significantly differ between admixed and parent populations. The
      simple arch fingerprint frequency decreases significantly in the admixed
      population in comparison with parent populations while both simple whorl
      fingerprint frequency and finger ridge counts increase significantly. True
      pattern frequency of the span area of interdigital III and IV areas on right
      hands and the radial-loop frequency of the right index fingers in the admixed
      populations are consistent with their matrilineal population. These
      dermatoglyphic changes may result from increased heterozygosity in the admixed
      population. The genetic modes of these changes may be relatively simple and will
      be useful for future dermatoglyph genetic studies.

PMID- 19167709
TI  - Physical examination of the foot and ankle by orthopaedic and accident and
      emergency clinicians.
AB  - Our aim was to test the knowledge of clinicians in the Orthopaedic clinic and in
      the Emergency department of the surface anatomical landmarks that should be
      examined routinely in the assessment of foot and ankle injuries. A survey of 109
      clinicians was conducted. Each participant was asked to palpate six important
      surface landmarks. Two participants failed to identify even a single landmark. Of
      109 assessed only 27% correctly identified all six landmarks. The mean number of
      landmarks correctly identified by each clinician was 4.1 with a standard
      deviation of 1.5 and range of 0-6. The knowledge of surface anatomy overall by
      junior Orthopaedic and Emergency clinicians was found to be very poor. Clinicians
      are becoming more reliant on potentially unnecessary and expensive imaging
      investigations. They have neglected the basic art of physical examination based
      on a sound knowledge of human anatomy. At present, the authors believe that the
      anatomical teaching that should begin in undergraduate medicine is inadequate.

PMID- 19167710
TI  - Insulin therapy induces changes in the inflammatory response in a murine 2-hit
      model.
AB  - Post-traumatic complications commonly seen on intensive care units include sepsis
      and associated disorders, which are accompanied by alterations in inflammatory
      cytokine expression patterns and in activation of neutrophils. Hyperglycaemia,
      often occurring after trauma and sepsis, is a further risk factor for morbidity
      and mortality among critically ill people. Clinical investigations have suggested
      that strict glycaemic control by insulin titration reduces overall mortality.
      This study aimed to further elucidate the pathophysiological and immunomodulative
      actions of insulin. Femoral fracture was induced in a murine model, followed by
      1h of haemorrhage. Two days after the first hit, sepsis was induced by caecal
      ligation and puncture (CLP). In control animals, laparotomy only was performed.
      Insulin in two different concentrations (10IU or 20IU) or vehicle was
      administered daily. Insulin therapy was associated with improvement of clinical
      parameters, slightly improved survival rates and, in lungs and liver, fewer
      infiltrating neutrophils and reduced IL-6 and IL-10 mRNA expression. These
      results suggested that, in this animal model, insulin had a direct anti
      inflammatory effect that was independent of modulation of blood glucose levels.

PMID- 19167711
TI  - Creating a therapeutic environment: a non-randomised controlled trial of a quiet
      time intervention for patients in acute care.
AB  - BACKGROUND: Noise is a significant barrier to sleep for acute care hospital
      patients, and sleep has been shown to be therapeutic for health, healing and
      recovery. Scheduled quiet time interventions to promote inpatient rest and sleep
      have been successfully trialled in critical care but not in acute care settings.
      OBJECTIVES: The study aim was to evaluate a scheduled quiet time intervention in
      an acute care setting. The study measured the effect of a scheduled quiet time on
      noise levels, inpatients' rest and sleep behaviour, and wellbeing. The study also
      examined the impact of the intervention on patients', visitors' and health
      professionals' satisfaction, and organisational functioning. DESIGN: The study
      was a multi-centred non-randomised parallel group trial. SETTINGS: The research
      was conducted in the acute orthopaedic wards of two major urban public hospitals
      in Brisbane, Australia. PARTICIPANTS: All patients admitted to the two wards in
      the 5-month period of the study were invited to participate, with a final sample
      of 299 participants recruited. This sample produced an effect size of 0.89 for an
      increase in the number of patients asleep during the quiet time. METHODS:
      Demographic data were collected to enable comparison between groups. Data for
      noise level, sleep status, sleepiness and wellbeing were collected using
      previously validated instruments: a Castle Model((c)) 824 digital sound level
      indicator; a three point sleep status scale; the Epworth Sleepiness Scale; and
      the SF12 V2 questionnaire. The staff, patient and visitor surveys on the
      experimental ward were adapted from published instruments. RESULTS: Significant
      differences were found between the two groups in mean decibel level and numbers
      of patients awake and asleep. The difference in mean measured noise levels
      between the two environments corresponded to a 'perceived' difference of 2 to 1.
      There were significant correlations between average decibel level and number of
      patients awake and asleep in the experimental group, and between average decibel
      level and number of patients awake in the control group. Overall, patients,
      visitors and health professionals were satisfied with the quiet time
      intervention. CONCLUSIONS: The findings show that a quiet time intervention on an
      acute care hospital ward can affect noise level and patient sleep/wake patterns
      during the intervention period. The overall strongly positive response from
      surveys suggests that scheduled quiet time would be a positively perceived
      intervention with therapeutic benefit.

PMID- 19167712
TI  - Statins inhibit Rho kinase activity in patients with atherosclerosis.
AB  - BACKGROUND: In addition to inhibiting cholesterol synthesis, statins (HMG-CoA
      reductase inhibitors) decrease the formation of isoprenoid intermediates required
      for the activation of key signaling pathways, including Rho/Rho kinase (ROCK). In
      experimental settings, statins inhibit ROCK and reverse vascular dysfunctions in
      atherosclerosis, independent of cholesterol reduction. It is not known whether
      statins inhibit ROCK activity in humans with atherosclerosis. METHODS: We
      investigated 35 patients with stable atherosclerosis in a randomized, double
      blind study comparing treatment with high-dose (80mg/d) or low-dose (10mg/d)
      atorvastatin to placebo for 28 days. Blood samples for leukocyte ROCK activity,
      fasting lipids, and high-sensitivity C-reactive protein (hs-CRP) were obtained on
      days 0, 7, 14, and 28 after randomization and change over time with the two
      statin treatments relative to placebo was examined. RESULTS: Atorvastatin 80mg/d
      reduced ROCK activity (p=0.002 vs. placebo). This decline was rapid and
      significant within 2 weeks of treatment. The inhibition of ROCK by atorvastatin
      (80mg/d) remained significant even after controlling for changes in low-density
      lipoprotein cholesterol (LDL-C) and triglycerides (p=0.01). Furthermore, there
      was no correlation between changes in ROCK activity and changes in LDL-C (r=0.2,
      p=0.25) or triglycerides (r=0.1, p=0.55). There was a modest correlation between
      ROCK inhibition and change in hs-CRP among patients randomized to atorvastatin
      80mg/d (r=0.6, p=0.07). CONCLUSIONS: These first-in-man findings demonstrate that
      high-dose atorvastatin rapidly inhibits the pro-atherogenic Rho/ROCK pathway,
      independent of cholesterol reduction. This inhibition may contribute to the
      clinical benefits of statins. Rho/ROCK may provide a useful therapeutic target in
      patients with atherosclerosis.

PMID- 19167713
TI  - Asymmetric dimethylarginine induces tissue factor expression in monocytes via NF
      kappaB-dependent pathway: Role in acute coronary syndromes.
AB  - Asymmetric dimethylarginine (ADMA), a major endogenous inhibitor of nitric oxide
      synthase, is recently defined as an independent cardiovascular risk factor.
      Tissue factor (TF) expression and procoagulant activity (PCA) of peripheral
      monocytes are increased in patients with acute coronary syndromes (ACS), which
      resulted in blood procoagulant state tending to thrombus formation. In the
      present study, we tested the hypothesis that ADMA contribute to TF expression of
      peripheral monocytes in ACS. Twenty patients with unstable angina (UA), 20
      patients with stable angina (SA) and 20 control subjects were recruited.
      Monocytic cell line THP-1 was incubated with different concentrations of ADMA (1
      10microM) for various periods (6-24h). Our results showed that plasma level of
      ADMA in patients with UA was significantly higher than those in patients with SA
      or in the control group, and positively correlated with TF antigen level and PCA
      of circulating monocytes. Adjusting for all patient characteristics, we confirmed
      these findings in multivariate regression analyses. In cultured THP-1 cells, ADMA
      transcriptionally upregulated both TF antigen expression and PCA in a
      concentration-dependent manner. The experiments using nuclear factor-kappaB (NF
      kappaB) inhibitor and transient transfection with wild-type and mutated TF
      promotor constructs showed that the NF-kappaB is an important transcriptional
      regulator of ADMA-induced TF expression. Our results suggest that elevated plasma
      level of ADMA induces TF expression in monocytes via NF-kappaB-dependent pathway,
      which contributes to procoagulant phenotype of circulating monocytes in ACS.

PMID- 19167714
TI  - Retention models for ionizable compounds in reversed-phase liquid chromatography:
      effect of variation of mobile phase composition and temperature.
AB  - General models in reversed-phase liquid chromatography that have been extended to
      relate retention of ionizable compounds to mobile phase composition, pH and/or
      temperature are reviewed. In particular, the fundamentals and applications of the
      solvation parameter model, the polarity parameter model and several classical
      models based on empirical equations are presented and compared. A main parameter
      in all these models is the degree of ionization of the acid-base compound, which
      depends on both the pH of the mobile phase and the acid-base constant of the
      compound. Thus, on one hand, the different procedures for pH measurement in the
      mobile phase and their influence on the performance of the models are outlined.
      On the other hand, equations that relate the variation of the pH of the buffer
      and the pK(a) of the compound with the mobile phase composition and/or
      temperature are reviewed and their applicability to the retention models
      critically discussed.

PMID- 19167715
TI  - Combined column-mobile phase mixture statistical design optimization of high
      performance liquid chromatographic analysis of multicomponent systems.
AB  - A statistical approach for the simultaneous optimization of the mobile and
      stationary phases used in reversed-phase liquid chromatography is presented.
      Mixture designs using aqueous mixtures of acetonitrile (ACN), methanol (MeOH) and
      tetrahydrofuran (THF) organic modifiers were performed simultaneously with column
      type optimization, according to a split-plot design, to achieve the best
      separation of compounds in two sample sets: one containing 10 neutral compounds
      with similar retention factors and another containing 11 pesticides. Combined
      models were obtained by multiplying a linear model for column type, C8 or C18, by
      quadratic or special cubic mixture models. Instead of using an objective response
      function, combined models were built for elementary chromatographic criteria
      (retention factors, resolution and relative retention) of each solute or pair of
      solutes and, after their validation, the global separation was accomplished by
      means of Derringer's desirability functions. For neutral compounds a 37:12:8:43
      (v/v/v/v) percentage mixture of ACN:MeOH:THF:H2O with the C18 column and for
      pesticides a 15:15:70 (v/v/v) ACN:THF:H2O mixture with the C8 column provide
      excellent resolution of all peaks.

PMID- 19167716
TI  - Efficient isolation of the subunits of recombinant and pituitary glycoprotein
      hormones.
AB  - Complete dissociation into subunits was attained by incubating Chinese hamster
      ovary (CHO)-derived or native human thyrotropin, follitropin and lutropin
      overnight at 37 degrees C in acetic acid. The alpha-and beta-subunits of the
      pituitary glycoprotein hormones were rapidly and quantitatively isolated by
      reversed-phase high-performance liquid chromatography (RP-HPLC). A dissociation
      efficiency of > 98% was obtained on the basis of mass determinations of the
      heterodimers and subunits carried out via mass spectrometry. CHO-derived or
      native subunits were isolated on a C4 column (80-90% total recovery) and
      characterized comparatively for purity, hydrophobicity, molecular mass and charge
      distribution by HPLC, mass spectrometry, sodium dodecylsulfate-polyacrylamide gel
      electrophoresis and isoelectric focusing. Thyrotropin was used as a model for
      showing that, after subunit reassociation, the in vivo bioactivity of the hormone
      was completely restored. The method described is mild, practical, flexible, and
      can be adapted to dissociate microgram amounts of native or recombinant
      glycoprotein hormones, allowing characterization of each subunit.

PMID- 19167717
TI  - Formation mechanism and morphology modulation of honeycomb hybrid films made of
      polyoxometalates/surfactants at the air/water interface.
AB  - Highly ordered honeycomb hybrid films of nanometer-scale polyoxometalates and
      surfactants were fabricated by a simple solvent-evaporation method at the
      air/water interface. A good template by micrometer water droplets which are
      condensed from water vapor because of the quick evaporation of organic solvents
      plays an important role in the self-patterning of honeycomb films. The
      morphologies of the thin films can be modulated by the solvent volatility which
      can not only influence the pore size of the film but also determine whether or
      not a regular porous structure can be achieved at all. The faster the volatility
      of organic solvents, the smaller the pores of films. Higher hydrophobicity and
      larger surface coverage which are induced by the surface encapsulation of a
      polyoxometalate by cationic surfactants with longer double carbon chains are
      beneficial to the organization of porous structures. It is also found that the
      morphologies of the thin films can be changed when the thin films are dropped at
      different supporting solution interfaces. It is well demonstrated that the
      morphologies of the fabricated hybrid films are modulated by appropriate
      controls.

PMID- 19167718
TI  - Simulation of the heteroagglomeration between highly size-asymmetric ceramic
      particles.
AB  - Aggregation phenomena of dilute suspensions composed of two kinds of oxide
      particles (alumina d(1)=400 nm and silica d(2)=25 nm) have been studied by
      computer simulations. These particles are oppositely charged and so are prone to
      heteroagglomerate. The interaction between particles has been modeled by the DLVO
      potential. Two kinds of simulations have been performed: Brownian dynamics
      simulations to study the aggregation kinetics and global minimization searches
      that permit the examination of the most stable configurations of agglomerates. We
      demonstrate that aggregation should occur also for quite large fractions of added
      silica (even when 200 silica particles are adsorbed on each alumina particle) and
      that aggregates are likely to present chainlike shapes. Both findings are in
      agreement with experiments.

PMID- 19167719
TI  - Influence of stuttering variation on talker group classification in preschool
      children: preliminary findings.
AB  - The purpose of this study was to investigate whether variations in disfluencies
      of young children who do (CWS) and do not stutter (CWNS) significantly change
      their talker group classification or diagnosis from stutterer to nonstutterer,
      and vice versa. Participants consisted of seventeen 3- to 5-year-old CWS and nine
      3- to 5-year-old CWNS, with no statistically significant between-group difference
      in chronological age (CWS: M=45.53 months, S.D.=8.32; CWNS: M=47.67 months,
      S.D.=6.69). All participants had speech, language, and hearing development within
      normal limits, with the exception of stuttering for CWS. Both talker groups
      participated in a series of speaking samples that varied by: (a) conversational
      partner [parent and clinician], (b) location [home and clinic], and (c) context
      [conversation and narrative]. The primary dependent measures for this study were
      the number of stuttering-like disfluencies (SLD) per total number of spoken words
      [%SLD] and the ratio of SLD to total disfluencies (TD) [SLD/TD]. The results
      indicated that significant variability of stuttering did not exist as a result of
      conversational partner or location. Changes in context, however, did impact the
      CWS, who demonstrated higher SLD/TD in the conversation sample versus a narrative
      sample. Consistent with hypotheses, CWS and CWNS were accurately identified as
      stutterers and nonstutterers, respectively, regardless of changes to
      conversational partner, location or context for the overall participant sample.
      Present findings were taken to suggest that during assessment, variations in
      stuttering frequency resulting from changes in conversational partner, location
      or context do not significantly influence the diagnosis of stuttering, especially
      for children not on the talker group classification borderline between CWS and
      CWNS. LEARNING OUTCOMES: Readers will be able to: (1) Describe the role of
      variability in stuttering frequency for young children who stutter; (2) Identify
      three fundamental measurements of the frequency of stuttering-like and
      nonstuttering-like disfluencies; (3) Describe the effects of stuttering variation
      on talker group classification of stuttering or nonstuttering.

PMID- 19167720
TI  - The status of the standards.

PMID- 19167721
TI  - Automated external defibrillators and simulated in-hospital cardiac arrests.
AB  - OBJECTIVE: To test the hypothesis that pediatric residents would have shorter
      time to attempted defibrillation using automated external defibrillators (AEDs)
      compared with manual defibrillators (MDs). STUDY DESIGN: A prospective,
      randomized, controlled trial of AEDs versus MDs was performed. Pediatric
      residents responded to a simulated in-hospital ventricular fibrillation cardiac
      arrest and were randomized to using either an AED or MD. The primary end point
      was time to attempted defibrillation. RESULTS: Sixty residents, 21 (35%) interns,
      were randomized to 2 groups (AED = 30, MD = 30). Residents randomized to the AED
      group had a significantly shorter time to attempted defibrillation [median, 60
      seconds (interquartile range, 53 to 71 seconds)] compared with those randomized
      to the MD group [median, 103 seconds (interquartile range, 68 to 288 seconds)] (P
      < .001). All residents in the AED group attempted defibrillation at <5 minutes
      compared with 23 (77%) in the MD group (P = .01). CONCLUSIONS: AEDs improve the
      time to attempted defibrillation by pediatric residents in simulated cardiac
      arrests. Further studies are needed to help determine the role of AEDs in
      pediatric in-hospital cardiac arrests.

PMID- 19167722
TI  - Differentiated thyroid carcinoma in pediatric patients: comparison of
      presentation and course between pre-pubertal children and adolescents.
AB  - OBJECTIVE: To evaluate the clinical characteristics, course, and outcome of
      differentiated thyroid carcinoma (DTC) in pre-pubertal children compared with
      adolescents. STUDY DESIGN: The records of 10 pre-pubertal and 17 pubertal
      patients in whom DTC was diagnosed and who were observed in our tertiary
      pediatric endocrine clinic were reviewed. Extension of tumor at presentation,
      treatment modality, course, and outcome were analyzed. RESULTS: A positive family
      history of DTC was more prevalent in the pre-pubertal group (P = .037). At
      diagnosis, they had a greater degree of extrathyroid extension (P = .012), lymph
      node involvement (P = .009), and lung metastases (P = .009). The extent of
      surgery was similar in both groups, whereas the weight-adjusted radioiodine
      (I(131)) ablative dose was higher in the pre-pubertal group (P = .004). During
      the median follow-up of 5 years, the overall survival rate was 100% for both
      groups, with no significant difference in evidence of residual tumor after
      initial therapy or the recurrence rate. CONCLUSION: DTC has a more aggressive
      presentation in pre-pubertal children. Rigorous initial surgical and I(131)
      treatment, followed by thyrotropin suppression, was found to result in an outcome
      similar to that achieved in the pubertal group.

PMID- 19167723
TI  - Bone marrow transplantation in children with Hunter syndrome: outcome after 7 to
      17 years.
AB  - OBJECTIVE: To evaluate the effect of bone marrow transplantation in children with
      Hunter syndrome. STUDY DESIGN: Eight boys received a bone marrow graft between
      the ages of 3 and 16 years from 1990 to 2000. In 6 cases, the donor was a sibling
      with identical HLA status, in 1 case an unrelated donor with HLA-compatible, and
      in 1 case a mismatched unrelated donor. A complete multidisciplinary evaluation
      was performed yearly. RESULTS: Successful engraftment was achieved in all
      patients, with the proportion of donor cells reaching > or =95% 1 month after
      transplantation in all patients. Patients have been followed from between 7 and
      17 years and all are still alive, except for 1 boy who died at the age of 10 from
      unrelated causes. Cardiovascular abnormalities stabilized in all patients,
      hepatosplenomegaly resolved, and joint stiffness improved, Perceptual hearing
      defects remained stable, and transmission hearing defects improved. Only 1 child
      required subsequent surgery to correct kyphosis. Neuropsychological outcome was
      variable and appeared to be related to the severity of the syndrome. CONCLUSIONS:
      Bone marrow transplantation is effective on the no neuropsychological symptoms of
      Hunter disease.

PMID- 19167724
TI  - Submaximal treadmill test predicts VO2max in overweight children.
AB  - OBJECTIVE: To demonstrate the ability of a submaximal test to predict VO(2max) in
      overweight children. STUDY DESIGN: A total of 130 children, 11 to 14 years old,
      with body mass index >85 percentile for age and sex performed a submaximal
      walking test. VO(2max) was measured by using open circuit spirometry during a
      graded exercise test to volitional fatigue. An equation to predict VO(2max) was
      modeled by using the variables of sex, weight (kg), height (cm), heart rate (HR)
      after 4 minutes during the submaximal test (4minHR), HR difference (4minHR -
      resting HR), and submaximal treadmill speed (miles per hour [mph]) in 75% of the
      subjects. Validation was performed by using the remaining 25% of subjects.
      RESULTS: A total of 113 subjects achieved a maximal effort and was used in the
      statistical analysis. Development and validation groups were similar in all
      aspects. On validation, the mean square error was 241.06 with the predicted
      VO(2max) within 10% of the observed value in 67% of subjects. CONCLUSION:
      VO(2max) was accurately predicted in this cohort of overweight children by using
      a submaximal, treadmill-based testing protocol.

PMID- 19167725
TI  - The short- and long-term effects of simple behavioral interventions for nocturnal
      enuresis in young children: a randomized controlled trial.
AB  - OBJECTIVE: To assess the short- and long-term effects of 3 simple behavioral
      interventions to overcome nocturnal enuresis in young children. STUDY DESIGN: We
      performed a randomized controlled trial in children aged four to five years with
      mono-symptomatic nocturnal enuresis (n = 570). The children were placed in one of
      four groups: (1) lifting to urinate and ask for a password; (2) the same as group
      1, without a password; (3) using a reward system; or (4) a control group. Each
      participant was asked to carry out the appointed intervention for 6 months or
      until 14 consecutive dry nights occurred, which was the continence criterion. A
      follow-up was performed approximately 3 years after the study. RESULTS: After 6
      months, lifting the child to the toilet without the use of a password was the
      only intervention that resulted in significantly more dry children (37%) than the
      control group (21%). Three years later, both lifting groups had the highest (78%)
      and the control group the lowest (69%) percentage of dry children. CONCLUSIONS:
      The intervention lifting to urinate without the use of a password leads to more
      dry children compared with no active treatment in children aged 4 to 5 years with
      nocturnal enuresis.

PMID- 19167727
TI  - Report of two Chinese families and a review of Mainland Chinese CADASIL patients.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease caused by a
      mutation of the NOTCH3 gene. The clinical information of two CADASIL families was
      studied and mutation analysis of the NOTCH3 gene was performed by DNA direct
      sequencing. Published studies of Mainland Chinese CADASIL patients were reviewed
      and reanalyzed. The patients in the two families showed migraine with aura,
      stroke and cognitive decline. Cranial MRI revealed subcortical white matter
      infarcts and leukoencephalopathy. Two previously reported mutations of the NOTCH3
      gene, c.397C>T and c.268C>T, were identified and cosegregated with the disease.
      The main clinical features, cranial MRI and pathological changes in Mainland
      Chinese CADASIL patients were similar to those in other regions. The frequency of
      migraine may be lower than that in Europe, but similar to that in Asia. Eight
      different NOTCH3 gene mutations were reported among Mainland Chinese CADASIL
      patients; of these, the c.322C>T mutation has not been reported in other regions.
      This study supports that the clinical features of Mainland Chinese CADASIL
      patients are similar to those seen in other regions and that exon 3 and exon 4 of
      the NOTCH3 gene are the mutation hotspots in Mainland Chinese CADASIL patients.

PMID- 19167728
TI  - Fractal dimension analysis of grey matter in multiple sclerosis.
AB  - The fractal dimension (FD) is a quantitative parameter that characterizes the
      morphometric variability of a complex object. Among other applications, FD has
      been used to identify abnormalities of the human brain in conventional magnetic
      resonance imaging (MRI), including white matter abnormalities in patients with
      Multiple Sclerosis (MS). Extensive grey matter (GM) pathology has been recently
      identified in MS and it appears to be a key factor in long-term disability. The
      aim of the present work was to assess whether FD measurement of GM in T1 MRI
      sequences can identify GM abnormalities in patients with MS in the early phase of
      the disease. A voxel-based morphometry approach optimized for MS was used to
      obtain the segmented brain, where we later calculated the three-dimensional FD of
      the GM in MS patients and healthy controls. We found that patients with MS had a
      significant increase in the FD of the GM compared to controls. Such differences
      were present even in patients with short disease durations, including patients
      with first attacks of MS. In addition, the FD of the GM correlated with T1 and T2
      lesion load, but not with GM atrophy or disability. The FD abnormalities of the
      GM here detected differed from the previously published FD of the white matter in
      MS, suggesting that different pathological processes were taking place in each
      structure. These results indicate that GM morphology is abnormal in patients with
      MS and that this alteration appears early in the course of the disease.

PMID- 19167729
TI  - Attention to somatosensory events is directly linked to the preparation for
      action.
AB  - The present study investigated the neural basis of attention in the somato
      sensory system. Subjects directed their attention towards their left or right
      hand while functional MRI data was collected during tactile stimulation of the
      fingers. Activations evoked by tactile stimuli when a stimulated hand was
      attended vs. unattended were contrasted. The tactile stimuli elicited hemodynamic
      responses in the contralateral primary and secondary somatosensory cortex. No
      attentional modulations of the BOLD-response could be observed in these regions.
      However, attention-related modulations were observed at more anterior locations
      in the ipsi- and contralateral primary motor cortex and in the supplementary
      motor area. This pattern of results suggests, that attention to somato-sensory
      events is directly linked to the motor system and the preparation for action.
      This mechanism appears to be in stark contrast to visual or auditory attention,
      which primarily serve to separate relevant from irrelevant information.

PMID- 19167732
TI  - Nomograms for predicting graft function and survival in living donor kidney
      transplantation based on the UNOS Registry.
AB  - PURPOSE: We developed nomograms that predict transplant renal function at 1 year
      (Modification of Diet in Renal Disease equation [estimated glomerular filtration
      rate]) and 5-year graft survival after living donor kidney transplantation.
      MATERIALS AND METHODS: Data for living donor renal transplants were obtained from
      the United Network for Organ Sharing registry for 2000 to 2003. Nomograms were
      designed using linear or Cox regression models to predict 1-year estimated
      glomerular filtration rate and 5-year graft survival based on pretransplant
      information including demographic factors, immunosuppressive therapy,
      immunological factors and organ procurement technique. A third nomogram was
      constructed to predict 5-year graft survival using additional information
      available by 6 months after transplantation. These data included delayed graft
      function, any treated rejection episodes and the 6-month estimated glomerular
      filtration rate. The nomograms were internally validated using 10-fold cross
      validation. RESULTS: The renal function nomogram had an r-square value of 0.13.
      It worked best when predicting estimated glomerular filtration rate values
      between 50 and 70 ml per minute per 1.73 m(2). The 5-year graft survival
      nomograms had a concordance index of 0.71 for the pretransplant nomogram and 0.78
      for the 6-month posttransplant nomogram. Calibration was adequate for all
      nomograms. CONCLUSIONS: Nomograms based on data from the United Network for Organ
      Sharing registry have been validated to predict the 1-year estimated glomerular
      filtration rate and 5-year graft survival. These nomograms may facilitate
      individualized patient care in living donor kidney transplantation.

PMID- 19167731
TI  - Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly
      reduces risk of metastases and improves survival: long-term followup of a
      randomized clinical trial.
AB  - PURPOSE: Extraprostatic disease will be manifest in a third of men after radical
      prostatectomy. We present the long-term followup of a randomized clinical trial
      of radiotherapy to reduce the risk of subsequent metastatic disease and death.
      MATERIALS AND METHODS: A total of 431 men with pT3N0M0 prostate cancer were
      randomized to 60 to 64 Gy adjuvant radiotherapy or observation. The primary study
      end point was metastasis-free survival. RESULTS: Of 425 eligible men 211 were
      randomized to observation and 214 to adjuvant radiation. Of those men under
      observation 70 ultimately received radiotherapy. Metastasis-free survival was
      significantly greater with radiotherapy (93 of 214 events on the radiotherapy arm
      vs 114 of 211 events on observation; HR 0.71; 95% CI 0.54, 0.94; p = 0.016).
      Survival improved significantly with adjuvant radiation (88 deaths of 214 on the
      radiotherapy arm vs 110 deaths of 211 on observation; HR 0.72; 95% CI 0.55, 0.96;
      p = 0.023). CONCLUSIONS: Adjuvant radiotherapy after radical prostatectomy for a
      man with pT3N0M0 prostate cancer significantly reduces the risk of metastasis and
      increases survival.

PMID- 19167726
TI  - Long-term budesonide or nedocromil treatment, once discontinued, does not alter
      the course of mild to moderate asthma in children and adolescents.
AB  - OBJECTIVES: To determine whether long-term, continuous use of inhaled anti
      inflammatory medications affects asthma outcomes in children with mild to
      moderate asthma after use is discontinued. STUDY DESIGN: Of the 1041 participants
      in the Childhood Asthma Management Program randomized clinical trial, 941 (90%)
      were followed to determine whether 4.3 years of twice-daily budesonide or
      nedocromil administration (each compared with placebo) affected subsequent asthma
      outcomes during a 4.8-year posttrial period in which treatment was managed by the
      participants' physicians. RESULTS: The groups treated continuously during the
      trial with either budesonide or nedocromil did not differ from the group given
      placebo in terms of lung function, control of asthma, or psychological status at
      the end of 4.8 years of posttrial follow-up. However, the decreased mean height
      in the budesonide group relative to the placebo group at the end of the trial
      (1.1 cm; P = .005) remained statistically significant (0.9 cm; P = .01) after an
      additional 4.8 years and was more pronounced in girls (1.7 cm; P = .001) than in
      boys (0.3 cm; P = .49). Participants in all groups used inhaled corticosteroids
      during 30% of the posttrial period. CONCLUSIONS: Clinically meaningful
      improvements in the control of asthma and in airway responsiveness achieved
      during continuous treatment with inhaled corticosteroids do not persist after
      continuous treatment is discontinued.

PMID- 19167735
TI  - [Tibial cortical bone graft and pre-implant surgery].
AB  - In pre-implant surgery, the autologous bone graft can be harvested from various
      sites. The tibial diaphysis cortical bone gives a very dense graft which does not
      resorb. It can be crushed for sinus filling, or used in a monoblock as apposition
      graft or to repair alveolar cleft sequels. Its availability, its simple and
      speedy harvesting, and its very low morbidity make it a good choice for most pre
      implant reconstructive procedures.

PMID- 19167733
TI  - A double-blind randomized crossover study of oral thalidomide versus placebo for
      androgen dependent prostate cancer treated with intermittent androgen ablation.
AB  - PURPOSE: We determined whether thalidomide can prolong progression-free survival
      in men with biochemically recurrent prostate cancer treated with limited androgen
      deprivation therapy. MATERIALS AND METHODS: A total of 159 patients were enrolled
      in a double-blind randomized trial to determine if thalidomide can improve the
      efficacy of a gonadotropin-releasing hormone agonist in hormone responsive
      patients with an increasing prostate specific antigen after primary definitive
      therapy for prostate cancer. Patients were randomized to 6 months of gonadotropin
      releasing hormone agonist followed by 200 mg per day oral thalidomide or placebo
      (oral phase A). At the time of prostate specific antigen progression gonadotropin
      releasing hormone agonist was restarted for 6 additional months. Patients were
      then crossed over to the opposite drug and were treated until prostate specific
      antigen progression (oral phase B). Testosterone and dihydroxytestosterone were
      likewise monitored throughout the study. RESULTS: During oral phase A the median
      time to prostate specific antigen progression was 15 months for the thalidomide
      group compared to 9.6 months on placebo (p = 0.21). The median time to prostate
      specific antigen progression during oral phase B for the thalidomide group was
      17.1 vs 6.6 months on placebo (p = 0.0002). No differences in time to serum
      testosterone normalization between the thalidomide and placebo arms were
      documented during oral phase A and oral phase B. Thalidomide was tolerable
      although dose reductions occurred in 47% (58 of 124) of patients. CONCLUSIONS:
      Despite thalidomide having no effect on testosterone normalization, there was a
      clear effect on prostate specific antigen progression during oral phase B. This
      is the first study to our knowledge to demonstrate the effects of thalidomide
      using intermittent hormonal therapy.

PMID- 19167734
TI  - An evaluation of the health status of the Lavaca Bay, Texas ecosystem using
      Crassostrea virginica as the sentinel species.
AB  - Locational risks for compromised ecosystem health for the eastern oysters
      (Crassostrea virginica) harvested from Lavaca Bay, Texas were estimated. Flow
      cytometric evaluation of variations in DNA content and the lysosomal
      destabilization assay were used for evaluation of genotoxicity and stress,
      respectively. Bayesian geo-statistical methods were utilized to estimate and
      evaluate spatial effects. For models with spatial risks, continuous surface maps
      of predicted parameter values were created to evaluate risk location. Lysosomal
      destabilization assay results were spatially oriented whereas flow cytometry
      results were fit best with the random effects model. While not spatially
      oriented, the highest levels of variations in DNA content were also present near
      industrial facilities. Locational risks of increased biomarkers of genotoxicity
      and stress in the eastern oyster (Crassostrea virginica) were increased with
      proximity to industrial facilities.

PMID- 19167736
TI  - [Sinus pericranii: a rare transcranial venous anomaly].
AB  - INTRODUCTION: Sinus pericranii is a rare midline cranial venous anomaly. It
      should be diagnosed radiologically. We report an asymptomatic case in a six-year
      old female patient. CASE REPORT: The patient consulted for a congenital
      asymptomatic bluish mediofrontal swelling. The complaint was strictly esthetic. A
      color US and MR angiography allowed diagnosing a sinus pericranii. Simple
      surveillance was decided because of a limited esthetic prejudice and the absence
      of any functional disorder. DISCUSSION: Sinus pericranii is a communication
      between extra- and intracranial venous systems. Its diagnosis is suspected when a
      subcutaneous mass is located on the scalp close to the midline, the volume of
      which changes with the head's position. It is confirmed by MRI, which usually
      shows a drainage in the superior sagittal sinus. Surgical treatment is a complex
      procedure and rarely indicated. A simple follow-up is often proposed because of
      the usual absence of complications.

PMID- 19167737
TI  - Effect of different ascorbate supplementations on in vitro cartilage formation in
      porcine high-density pellet cultures.
AB  - Articular cartilage has only very limited potential for self-repair and
      regeneration. For this reason, various tissue engineering approaches have been
      developed to generate cartilage tissue in vitro. Usually, most strategies require
      ascorbate supplementation to promote matrix formation by isolated chondrocytes.
      In this study, we evaluate and compare the effect of different ascorbate forms
      and concentrations on in vitro cartilage formation in porcine chondrocyte high
      density pellet cultures. l-ascorbate, sodium l-ascorbate, and l-ascorbate-2
      phosphate were administered in 100 microM, 200 microM, and 400 microM in the
      culture medium over 16 days. Pellet thickness increased independently from the
      supplemented ascorbate form and concentration. Hydroxyproline content increased
      as well, but here, medium concentration of AsAP and low concentration of AsA
      showed a more pronounced effect. Proteoglycan and collagen formation were
      evaluated histologically and could be proven in all supplemented cultures. Non
      supplemented cultures, however, showed no stable matrix formation at all. Effects
      on the gene expression pattern of cartilage marker genes (type I and type II
      collagen, aggrecan, and cartilage oligomeric matrix protein (COMP)) were studied
      by real-time RT-PCR and compared to non-supplemented control cultures. Expression
      level of cartilage marker genes was elevated in all cultures showing that
      dedifferentiation of chondrocytes could be prevented. Again, all supplementations
      caused a similar effect except for low concentration of AsA, which resulted in an
      even higher expression level of all marker genes. Besides that, we could not
      detect a pronounced difference between ascorbate and its derivates as well as
      between the different concentrations.

PMID- 19167738
TI  - Glycoprofile of the different cell types present in the mucosa of the horse
      guttural pouches.
AB  - Histochemical characterization of the equine guttural pouches was performed using
      lectins combined with sialidase digestion and deglycosylation pre-treatments. The
      goblet cells contained O- and N-linked oligosaccharides with alpha-Fuc, GlcNAc
      moieties whereas beta-GalNAc, beta-Gal-(1-3)-GalNAc, beta-Gal-(1-4)-GlcNAc and
      alpha-Gal residues belonged only to O-linked glycoproteins. The acinar and ductal
      cells expressed alpha-Man/alpha-Glc in N-linked oligosaccharides, GlcNAc in both
      O- and N-glycoproteins and beta-GalNAc, beta-Gal-(1-3)-GalNAc, beta-Gal-(1-4)
      GlcNAc and alpha-Gal residues included in O-linked glycoproteins. The Golgi area
      of the epithelial lining expressed alpha-Fuc in O-linked glycoproteins, internal
      GlcNAc in N-linked glycoproteins and large amounts of sialic acid residues linked
      to subterminal beta-GalNAc, Galbeta1,4GlcNAc and Galbeta1,3GalNAc. High amounts
      of sulpho-carbohydrates and of sialic acids (alpha2,3-6), linked to-alpha/beta
      Gal and sialic acids (alpha2-6) linked to beta-GalNAc, were also demonstrated.
      Such diversity of the mucin saccharide residues may be implicated in the binding
      of macromolecules such as those of bacterial or viral etiology, thus playing a
      role in the organism's host-defense mechanism in the guttural pouches.

PMID- 19167739
TI  - Phylogeny, classification and evolutionary insights into pestiviruses.
AB  - The genus Pestivirus comprises four established species: Bovine viral diarrhoea
      viruses 1 (BVDV-1) and 2 (BVDV-2), Border disease virus (BDV), and Classical
      swine fever virus (CSFV); and a tentative species, Pestivirus of giraffe.
      Additional pestiviruses have been identified and suggested for recognition as
      novel subgroups/species. To achieve a reliable phylogeny as the basis for
      classification of pestiviruses, a molecular dataset of 56 pestiviruses and 2089
      characters, comprising the 5'UTR, complete N(pro) and E2 gene regions was
      analysed by Maximum likelihood and Bayesian approach. An identical, robust tree
      topology was inferred, where seven well-supported monophyletic clades and two
      highly divergent lineages were identified. Dating most recent common ancestor was
      estimated for major pestivirus lineages and their evolutionary histories were
      revealed. Accordingly, a new proposal is presented for the classification of
      pestiviruses into nine species: BVDV-1, BVDV-2, BVDV-3 (atypical bovine
      pestiviruses), Pestivirus of giraffe, CSFV, BDV, Tunisian sheep virus (TSV;
      previously termed "Tunisian isolates"), Antelope and Bungowannah.

PMID- 19167741
TI  - Improving the spatial orientation of human teeth using a virtual 3D approach.
AB  - Since teeth are resistant to decomposition processes, they provide important and
      at times unique sources of information about fossil humans. Fortunately, dental
      remains reflect significant evolutionary changes. These changes make a very
      important and often exclusive contribution to the definition of new taxa or the
      attribution of fossil specimens to existing taxa. The traditional approach to
      dental morphometric analyses usually focuses on the recording of several measures
      of the tooth with calipers, especially the two basic crown diameters
      (buccolingual and mesiodistal). However, since these measures do not adequately
      represent the complex morphology of the tooth, 2D images and 3D digital models of
      dental morphology have been used. For both types of analysis, the possibility of
      correctly comparing homologous teeth depends on the adoption of a common
      orientation system. The lack of such a system makes it difficult to compare the
      results of different studies. Here we describe a new method for orienting teeth
      specifically devised for the upper and lower first molar (M1). Samples of unworn
      maxillary (n=15) and mandibular (n=15) first molars of modern humans were scanned
      with a Roland Picza 3D digitizer. The 3D virtual models were used to compare our
      new orientation method with those proposed in the literature. The new orientation
      system, which meets a geometric criterion, is based on three points identified on
      the cervical line and ensures acceptable repeatability of the spatial positioning
      and orientation independent of the shape and wear of the first molar under
      investigation. This orientation system is a first step toward the creation of a
      virtual set of hominid and fossil human first molars, which will allow us to make
      comparisons via a sophisticated and noninvasive approach. This pilot study also
      provides guidelines to extend the new methodology to the other types of teeth.

PMID- 19167742
TI  - Monitoring of the evolution of an industrial compost and prediction of some
      compost properties by NIR spectroscopy.
AB  - Sewage treatment plants produce wastes resulting from the organic matter
      concentration in the form of sludge. A way of jointly treating and exploiting
      these increasing wastes jointly is the composting. Composting makes it possible
      to reduce volumes and the masses of wastes all while developing them in a product
      usable like organic soil enrichment. In this work, the composting process of an
      industrial sewage sludge composting plant was monitored to study the evolution of
      different physico-chemical parameters (temperature, moisture, pH, organic carbon,
      organic and inorganic nitrogen, organic carbon/organic nitrogen ratio, humic
      substances) and biochemical parameters (soluble fraction, hemicellulose,
      cellulose, lignin). Because these analyses are expensive and time consuming, we
      wanted to develop an alternative method to determine the maturity of compost
      related to compost properties with raw samples. Acceptable predictions were found
      for moisture, temperature, pH, organic carbon, organic carbon/organic nitrogen
      ratio, total-, organic- and ammoniacal nitrogen, fulvic- and humic acids and
      fulvic acids/humic acids ratio, but the error values were too high for the
      compost age to consider a quantification model. With regard to the biochemical
      parameters, this study is rather a preliminary test which shows the interest of
      the approach, but requires to be continued. Finally, the age of compost can be
      evaluated with Principal Component Analysis applied to NIR spectra.

PMID- 19167740
TI  - Highly complex neutralization determinants on a monophyletic lineage of newly
      transmitted subtype C HIV-1 Env clones from India.
AB  - Little is known about the neutralization properties of HIV-1 in India to
      optimally design and test vaccines. For this reason, a functional Env clone was
      obtained from each of ten newly acquired, heterosexually transmitted HIV-1
      infections in Pune, Maharashtra. These clones formed a phylogenetically distinct
      genetic lineage within subtype C. As Env-pseudotyped viruses the clones were
      mostly resistant to IgG1b12, 2G12 and 2F5 but all were sensitive to 4E10. When
      compared to a large multi-subtype panel of Env-pseudotyped viruses (subtypes B, C
      and CRF02_AG) in neutralization assays with a multi-subtype panel of HIV-1
      positive plasma samples, the Indian Envs were remarkably complex. With the
      exception of the Indian Envs, results of a hierarchical clustering analysis
      showed a strong subtype association with the patterns of neutralization
      susceptibility. From these patterns we were able to identify 19 neutralization
      cluster-associated amino acid signatures in gp120 and 14 signatures in the
      ectodomain and cytoplasmic tail of gp41. We conclude that newly transmitted
      Indian Envs are antigenically complex in spite of close genetic similarity.
      Delineation of neutralization-associated amino acid signatures provides a deeper
      understanding of the antigenic structure of HIV-1 Env.

PMID- 19167743
TI  - Model testing of radioactive contamination by 90Sr, 137Cs and 239,240Pu of water
      and bottom sediments in the Techa River (Southern Urals, Russia).
AB  - This paper presents results of testing models for the radioactive contamination
      of river water and bottom sediments by (90)Sr, (137)Cs and (239,240)Pu. The
      scenario for the model testing was based on data from the Techa River (Southern
      Urals, Russia), which was contaminated as a result of discharges of liquid
      radioactive waste into the river. The endpoints of the scenario were model
      predictions of the activity concentrations of (90)Sr, (137)Cs and (239,240)Pu in
      water and bottom sediments along the Techa River in 1996. Calculations for the
      Techa scenario were performed by six participant teams from France (model
      CASTEAUR), Italy (model MARTE), Russia (models TRANSFER-2, CASSANDRA, GIDRO-W)
      and Ukraine (model RIVTOX), all using different models. As a whole, the
      radionuclide predictions for (90)Sr in water for all considered models, (137)Cs
      for MARTE and TRANSFER-2, and (239,240)Pu for TRANSFER-2 and CASSANDRA can be
      considered sufficiently reliable, whereas the prediction for sediments should be
      considered cautiously. At the same time the CASTEAUR and RIVTOX models estimate
      the activity concentrations of (137)Cs and (239,240)Pu in water more reliably
      than in bottom sediments. The models MARTE ((239,240)Pu) and CASSANDRA ((137)Cs)
      evaluated the activity concentrations of radionuclides in sediments with about
      the same agreement with observations as for water. For (90)Sr and (137)Cs the
      agreement between empirical data and model predictions was good, but not for all
      the observations of (239,240)Pu in the river water-bottom sediment system. The
      modelling of (239,240)Pu distribution proved difficult because, in contrast to
      (137)Cs and (90)Sr, most of models have not been previously tested or validated
      for plutonium.

PMID- 19167744
TI  - First birth of an animal from an extinct subspecies (Capra pyrenaica pyrenaica)
      by cloning.
AB  - Two experiments have been performed to clone the bucardo, an extinct wild goat.
      The karyoplasts were thawed fibroblasts derived from skin biopsies, obtained and
      cryopreserved in 1999 from the last living specimen, a female, which died in
      2000. Cytoplasts were mature oocytes collected from the oviducts of superovulated
      domestic goats. Oocytes were enucleated and coupled to bucardo's fibroblasts by
      electrofusion. Reconstructed embryos were cultured for 36h or 7d and transferred
      to either Spanish ibex or hybrid (Spanish ibex malex domestic goat) synchronized
      recipients. Embryos were placed, according to their developmental stage, into the
      oviduct or into the uterine horn ipsilateral to an ovulated ovary. Pregnancy was
      monitored through their plasmatic PAG levels. In Experiment 1, 285 embryos were
      reconstructed and 30 of them were transferred at the 3- to 6-cells stage to 5
      recipients. The remaining embryos were further cultured to day 7, and 24 of them
      transferred at compact morula/blastocyst stage to 8 recipients. In Experiment 2,
      154 reconstructed embryos were transferred to 44 recipients at the 3- to 6-cells
      stage. Pregnancies were attained in 0/8 and 7/49 of the uterine and oviduct
      transferred recipients, respectively. One recipient maintained pregnancy to term,
      displaying very high PAG levels. One morphologically normal bucardo female was
      obtained by caesarean section. The newborn died some minutes after birth due to
      physical defects in lungs. Nuclear DNA confirmed that the clone was genetically
      identical to the bucardo's donor cells. To our knowledge, this is the first
      animal born from an extinct subspecies.

PMID- 19167745
TI  - Cytoplasmic lipid droplets and mitochondrial distribution in equine oocytes:
      Implications on oocyte maturation, fertilization and developmental competence
      after ICSI.
AB  - Lipid droplets (LDs) and mitochondria in the ooplasm are essential for energy
      production required for maturation, fertilization and embryo development. This
      study investigates the correlations between cytoplasmic LDs polar aggregation
      and: (1) nuclear maturation (Experiment 1); (2) mitochondrial (mt) distribution
      pattern and localization (Experiment 2); (3) fertilization and embryonic
      development after intracytoplasmic sperm injection (ICSI; Experiment 3) in equine
      oocytes recovered from slaughtered mares and matured in vitro. Morphologically
      normal oocytes were selected after culture and categorized as having polar (P)
      aggregation or uniform (U) distribution of LDs. In Experiment 1, the maturation
      rate was significantly higher in P compared with U oocytes (69%, 40/58 vs. 32%,
      13/41; P<0.001). In Experiment 2, it was observed that P and U oocytes showed
      heterogeneous mt distribution at comparable rates (68%, 25/37 vs. 50%, 2/4 for P
      and U respectively; NS). Moreover, only in 8/25 (32%) of P oocytes, LDs
      overlapped with mt aggregates in the area containing meiotic spindle. In
      Experiment 3, normal fertilization (51%, 19/37 vs. 60%, 6/10, for P and U) and
      cleavage rates (83%, 20/24 vs. 67%, 4/6, for P and U) did not differ between
      groups, also in oocytes with LDs located nearby the polar body. Overall, P
      aggregation of LDs was related to cumulus expansion at collection. In conclusion,
      in equine matured oocytes, P aggregation of LDs is related with cumulus expansion
      and nuclear maturation. However, it is not related with heterogeneous mt
      distribution and cannot be considered a predictive indicator for normal
      fertilization and embryo development.

PMID- 19167746
TI  - The reproductive performance of female Formosan sambar deer (Cervus unicolor
      swinhoei) in semi-domesticated herds.
AB  - This study documented the reproductive performance of 210 adult female Formosan
      sambar deer (FSD, Cervus unicolor swinhoei) from four semi-domesticated deer
      herds in Taiwan. An extensive analysis of 525 reproductive records from 2000 to
      2008, including the conditions of estrus, gestation, and parturition was
      conducted. The mean+/-S.E.M. lengths of the estrous cycle, gestation, and fawning
      interval were 18.2+/-0.5d (n=56), 258.6+/-0.3d (n=160), and 369.9+/-2.3d (n=122),
      respectively. Hand breeding was performed between June and December (n=494), with
      the majority (93.1%) occurring between July and October (P<0.05). Fawning
      occurred from February to September (n=318), and most frequently (83.0%) between
      April and June (P<0.05). Pregnancy rate per mating in FSD hinds was 64.4%. There
      was a 1.3:1 male-to-female ratio at birth (P<0.05) among 320 fawns, and only two
      cases of twinning (0.63%). The postnatal mortality rate was 6.6% (21/320), and
      the mortality rate in fawns before weaning did not exceed 8% on any farm.
      Fecundity was enhanced by high pregnancy rates and high offspring survival rates.
      This study provides baseline information on reproductive performance of FSD,
      which should be valuable to veterinarians and deer industry personnel for
      management of FSD on farms in subtropical countries.

PMID- 19167747
TI  - Effects of sociosexual environment on serum testosterone in captive male African
      rhinoceros.
AB  - The relationships between testosterone concentrations in male African rhinoceros
      and the presence of conspecific males and females were investigated. Serum
      testosterone concentrations were measured using enzyme-linked immunoassay (EIA)
      in 37 male black rhinoceros (Diceros bicornis) and 21 male white rhinoceros
      (Ceratotherium simum) housed at 37 institutions in the USA. Testosterone
      concentrations in both black (n=37) and white (n=21) rhinoceros males rose with
      increasing numbers of females present (P<0.05). Average testosterone
      concentrations also rose with an increased number of conspecific males (n=34) in
      black rhinoceros (P<0.05). However, no specific pattern was found among male
      white rhinoceros housed with other males. We inferred that introduction of
      females to a male may play an important role in stimulating libido and
      spermatogenesis. The similar response of black rhinoceros and white rhinoceros to
      increased numbers of females suggested that, at least historically, herd
      structure for blacks may have been more similar to whites than previously
      realized, and should be investigated further.

PMID- 19167748
TI  - Response to medical students' letter of solidarity with Gaza.

PMID- 19167749
TI  - Immunocompatibility properties of lipid-polymer hybrid nanoparticles with
      heterogeneous surface functional groups.
AB  - Here we report the immunological characterization of lipid-polymer hybrid
      nanoparticles (NPs) and propose a method to control the levels of complement
      activation induced by these NPs. This method consists of the highly specific
      modification of the NP surface with methoxyl, carboxyl, and amine groups. Hybrid
      NPs with methoxyl surface groups induced the lowest complement activation,
      whereas the NPs with amine surface groups induced the highest activation. All
      possible combinations among carboxyl, amine, and methoxyl groups also activated
      the complement system to a certain extent. All types of NPs activated the
      complement system primarily via the alternative pathway rather than the lectin
      pathway. The classical pathway was activated to a very small extent by the NPs
      with carboxyl and amine surface groups. Human serum and plasma protein binding
      studies showed that these NPs had different protein binding patterns. Studies of
      both complement activation and coagulation activation suggested that NPs with
      methoxyl surface groups might be an ideal candidate for drug delivery
      applications, since they are not likely to cause any immunological adverse
      reaction in the human body.

PMID- 19167750
TI  - Injectable in situ forming biodegradable chitosan-hyaluronic acid based hydrogels
      for cartilage tissue engineering.
AB  - Injectable, biodegradable scaffolds are important biomaterials for tissue
      engineering and drug delivery. Hydrogels derived from natural polysaccharides are
      ideal scaffolds as they resemble the extracellular matrices of tissues comprised
      of various glycosaminoglycans (GAGs). Here, we report a new class of
      biocompatible and biodegradable composite hydrogels derived from water-soluble
      chitosan and oxidized hyaluronic acid upon mixing, without the addition of a
      chemical crosslinking agent. The gelation is attributed to the Schiff base
      reaction between amino and aldehyde groups of polysaccharide derivatives. In the
      current work, N-succinyl-chitosan (S-CS) and aldehyde hyaluronic acid (A-HA) were
      synthesized for preparation of the composite hydrogels. The polysaccharide
      derivatives and composite hydrogels were characterized by FTIR spectroscopy. The
      effect of the ratio of S-CS and A-HA on the gelation time, microstructure,
      surface morphology, equilibrium swelling, compressive modulus, and in vitro
      degradation of composite hydrogels was examined. The potential of the composite
      hydrogel as an injectable scaffold was demonstrated by the encapsulation of
      bovine articular chondrocytes within the composite hydrogel matrix in vitro. The
      results demonstrated that the composite hydrogel supported cell survival and the
      cells retained chondrocytic morphology. These characteristics provide a potential
      opportunity to use the injectable, composite hydrogels in tissue engineering
      applications.

PMID- 19167751
TI  - Block poly(ester-urethane)s based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate)
      and poly(3-hydroxyhexanoate-co-3-hydroxyoctanoate).
AB  - A series of block poly(ester-urethane) poly(3/4HB-HHxHO) urethanes (abbreviated
      as PUHO) based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3/4HB-diol) and
      poly(3-hydroxyhexanoate-co-3-hydroxyoctanoate) (PHHxHO-diol) segments were
      synthesized by a facile way of melting polymerization using 1,6-hexamethylene
      diisocyanate (HDI) as the coupling agent, with different 3HB, 4HB, HHxHO
      compositions and segment lengths. The chemical structure, molecular weight and
      distribution were systematically characterized by (1)H, (13)C nuclear magnetic
      resonance spectrum (NMR), two-dimensional correlation spectroscopy (COSY ((1)H,
      (13)C) NMR), Fourier transform infrared spectroscopy (FTIR) and gel permeation
      chromatography (GPC). The thermal property was studied by differential scanning
      calorimetry (DSC) and thermogravimetric analysis (TGA). The hydrophilicity was
      investigated by static contact angle of water and CH(2)I(2). DSC revealed that
      the poly(3/4HB-HHxHO) urethanes are almost amorphous with a little crystallinity
      (less than 6%) and T(g) from -23 degrees C to -3 degrees C. The polyurethanes are
      more hydrophobic (water contact angle 88 degrees -117 degrees ) than the P3/4HB
      and PHHxHO raw materials. The lactate dehydrogenase (LDH) assay and platelet
      adhesion determination showed that the obtained polyurethanes have much higher
      platelet adhesion property than raw materials and common biodegradable polymers
      polylactic acid (PLA) and poly(3-hydroxybutyrate) (PHB). Hydrophobicity and
      crystallinity degree are important factors to affect the platelet adhesion. All
      the properties can be tailored by changing the composition and segment length of
      prepolymers P3/4HB-diol and PHHxHO-diol.

PMID- 19167752
TI  - Nanostructured biocomposite substrates by electrospinning and electrospraying for
      the mineralization of osteoblasts.
AB  - Nanotechnology has enabled the engineering of nanostructured materials to meet
      current challenges in bone replacement therapies. Biocomposite nanofibrous
      scaffolds of poly(l-lactic acid)-co-poly(epsilon-caprolactone), gelatin and
      hydroxyapatite (HA) were fabricated by combining the electrospinning and
      electrospraying techniques in order to create a better osteophilic environment
      for the growth and mineralization of osteoblasts. Electrospraying of HA
      nanoparticles on electrospun nanofibers helped to attain rough surface morphology
      ideal for cell attachment and proliferation and also achieve improved mechanical
      properties than HA blended nanofibers. Nanofibrous scaffolds showed high pore
      size and porosity up to 90% with fiber diameter in the range of 200-700 nm.
      Nanofibrous scaffolds were characterized for their functional groups and chemical
      structure by FTIR and XRD analysis. Studies on cell-scaffold interaction were
      carried out by culturing human fetal osteoblast cells (hFOB) on both HA blended
      and sprayed PLACL/Gel scaffolds and assessing their growth, proliferation,
      mineralization and enzyme activity. The results of MTS, ALP, SEM and ARS studies
      confirmed, not only did HA sprayed biocomposite scaffolds showed better cell
      proliferation but also enhanced mineralization and alkaline phosphatase activity
      (ALP) proving that electrospraying in combination with electrospinning produced
      superior and more suitable biocomposite nanofibrous scaffolds for bone tissue
      regeneration.

PMID- 19167753
TI  - Measuring mitochondrial and cytoplasmic Ca2+ in EGFP expressing cells with a low
      affinity calcium Ruby and its dextran conjugate.
AB  - The limited choice and poor performance of red-emitting calcium (Ca(2+))
      indicators have hampered microfluorometric measurements of the intracellular free
      Ca(2+) concentration in cells expressing yellow- or green-fluorescent protein
      constructs. A long-wavelength Ca(2+) indicator would also permit a better
      discrimination against cellular autofluorescence than the commonly used
      fluorescein-based probes. Here, we report an improved synthesis and
      characterization of Calcium Ruby, a red-emitting probe consisting of an extended
      rhodamine chromophore (578/602 nm peak excitation/emission) conjugated to BAPTA
      and having an additional NH(2) linker arm. The low-affinity variant (K(D,Ca)
      approximately 30 microM) with a chloride in meta position that was specifically
      designed for the detection of large and rapid Ca(2+) transients. While Calcium
      Ruby is a mitochondrial Ca(2+)probe, its conjugation, via the NH(2) tail, to a
      10,000 MW dextran abolishes the sub-cellular compartmentalization and generates a
      cytosolic Ca(2+) probe with an affinity matched to microdomain Ca(2+) signals. As
      an example, we show depolarization-evoked Ca(2+) signals triggering the
      exocytosis of individual chromaffin granules. Calcium Ruby should be of use in a
      wide range of applications involving dual- or triple labeling schemes or targeted
      sub-cellular Ca(2+) measurements.

PMID- 19167754
TI  - When can real-time quantitative RT-PCR effectively define molecular relapse in
      acute promyelocytic leukemia patients? (Results of the French Belgian Swiss APL
      Group).
AB  - 10-20% of APL patients relapse and the challenge remains to early identify these
      patients to improve survival rate. We report PML-RARalpha transcript detection by
      RQ-PCR in 260 consecutive APL patients (n = 970 samples). 223 patients with
      samples of sufficient RNA quality to demonstrate they reached molecular remission
      were monitored for MRD. During follow-up, 38 of these patients were tested
      positive for PML-RARalpha mRNA. 13 out of the 38 patients (34%) effectively
      developed hematological relapse. In the first positive sample, specific PML
      RARalpha NCN thresholds over which, or under which, patients could effectively be
      predicted to relapse or not, were identified and subsequently validated in a
      second cohort.

PMID- 19167755
TI  - The contribution of children's advocacy centers to felony prosecutions of child
      sexual abuse.
AB  - OBJECTIVE: To describe trends of felony sexual abuse prosecutions between 1992
      and 2002 for two districts of a large urban city that differed primarily in their
      use of children's advocacy centers (CACs) for sexual abuse evaluations in
      children. METHODS: Aggregate data for two districts of a large urban city were
      provided from 1992 to 2002 from the district attorney's office, child protective
      services (CPS) agency, and all CACs serving both districts. Summary statistics
      were calculated over time and compared between both districts for ecologic trends
      using negative binomial regression. RESULTS: Over the time period of the study,
      substantiated reports of child sexual abuse declined: District 1 experienced a
      59% decrease in the incidence of reports, while District 2 experienced a 49%
      decrease in the incidence of reports. Despite this decrease, felony prosecutions
      of child sexual abuse increased in District 1 (from 56.6 to 93.0
      prosecutions/100,000 children, rate ratio 1.64, 95% CI 1.38-1.95), but did not
      significantly increase in District 2 (from 58.0 to 54.9 prosecutions/100,000
      children, rate ratio 0.94, 95% CI 0.73-1.23); by 2002, the rate of felony
      prosecutions in District 1 was 69% greater (95% CI 37-109%) than the rate in
      District 2. In 1992, CACs in District 1 evaluated approximately 400 children,
      increasing to 1,187 children by 2002. The number of children evaluated by CACs in
      District 2 increased modestly from nearly 800 in 1992 to 1,000 in 2002.
      CONCLUSION: Felony prosecutions of child sexual abuse doubled in a district where
      the use of CACs nearly tripled, while no increase in felony prosecutions of child
      sexual abuse was found in a neighboring district, where the use of CACs remained
      fairly constant over time. PRACTICE IMPLICATIONS: Though many limitations exist
      when bringing together ecological data from different agencies, the strength of
      the association we observed between increased CAC use and increased felony
      prosecutions, and the stepwise fashion in which it occurred should support future
      research to confirm our findings and to delineate which attributes of CAC
      performance might impact the likelihood of prosecution of child sexual abuse.

PMID- 19167756
TI  - Physico-chemical, microbiological and ecotoxicological evaluation of a septic
      tank/Fenton reaction combination for the treatment of hospital wastewaters.
AB  - Hospital wastewater is considered a complex mixture populated with pathogenic
      microorganisms. The genetic constitution of these microorganisms can be changed
      through the direct and indirect effects of hospital wastewater constituents,
      leading to the appearance of antibiotic multi-resistant bacteria. To avoid
      environmental contamination hospital wastewaters must be treated. The objective
      of this study was to evaluate the efficiency of hospital wastewater treated by a
      combined process of biological degradation (septic tank) and the Fenton reaction.
      Thus, after septic tank biodegradation, batch Fenton reaction experiments were
      performed in a laboratory-scale reactor and the effectiveness of this sequential
      treatment was evaluated by a physico-chemical/microbiological time-course
      analysis of COD, BOD(5), and thermotolerant and total coliforms. The results
      showed that after 120min of Fenton treatment BOD(5) and COD values decreased by
      90.6% and 91.0%, respectively. The BOD(5)/COD ratio changed from 0.46 to 0.48
      after 120min of treatment. Bacterial removal efficiency reached 100%, while
      biotests carried out with Scenedesmus subspicatus and Daphnia magna showed a
      significant decrease in the ecotoxicity of hospital wastewater after the
      sequential treatment. The use of this combined system would ensure that neither
      multi-resistant bacteria nor ecotoxic substances are released to the environment
      through hospital wastewater discharge.

PMID- 19167757
TI  - Biochemical response in gilthead seabream (Sparus aurata) to in vivo exposure to
      a mix of selected PAHs.
AB  - In our previous studies we assessed the biochemical response of juvenile seabream
      to the exposure to three selected polycyclic aromatic hydrocarbons (PAHs)
      (phenanthrene, pyrene and fluorene) in short-term laboratory experiments. Since
      in the analyses conducted in the field it is much more natural to expect the
      presence of multiple contaminants at the same time, the objective of this study
      was to analyse the reaction of seabream to the exposure to a mix of the three
      PAHs tested previously. The proportions of the individual components in the PAH
      mix used in our experiments were constant and determined on the basis of the
      concentration addition concept. We measured a set of hepatic biomarkers: 7
      ethoxyresorufin-O-deethylase (EROD), glutathione-S-transferase (GST), catalase
      (CAT), superoxide dismutase (SOD) and lipid peroxidation; as well as biliary
      fluorescent aromatic compounds (FACs) metabolites. Moreover, we calculated the
      biotransformation index, the condition factor and the hepatosomatic index. Only a
      few of these indicators provided statistically significant response to the tested
      exposures, while FACs showed very strong increase with increasing concentration
      of the tested mix of PAHs. The results of this research are expected to
      contribute to the establishment of a good biochemical index of exposure to
      mixtures of PAHs in laboratory experiments, which can be further useful in field
      studies dealing with the impact of organic pollutants on marine organisms.

PMID- 19167758
TI  - Down-regulatory effect of alpha 1-acid glycoprotein on bovine neutrophil
      degranulation.
AB  - In this paper, the possible involvement of the acute phase protein alpha(1)-acid
      glycoprotein (AGP) in the local immunomodulation of inflammation was
      investigated. The dose response of bovine neutrophils to AGP as to mobilization
      of primary and secondary granules was studied. It was found that AGP fulfils a
      protective role against spontaneous exocytosis of secondary, but not primary,
      granules. This downregulatory effect is much more evident when degranulation is
      challenged with Zymosan activated serum (ZAS). AGP activity is dose-dependent,
      the acute phase concentration being more active than the physiological one.
      Carbohydrate moiety of AGP was found to be critical, since experimentally
      desialylated protein does not maintain its exocytosis-modulatory activity. The
      fact that AGP may modulate the degranulation of neutrophils confirms the
      hypothesis that AGP is heavily involved in the fine tuning of neutrophil activity
      in the inflammatory environment.

PMID- 19167759
TI  - HLA-association of serum levels of natural antibodies.
AB  - Natural antibodies of IgM or IgG types are present in sera of most healthy
      individuals and are important participants of the immune response. Little is
      known, however, about the genetic regulation of their plasma levels in humans. We
      determined the concentrations of three IgM type natural autoantibodies (NAAbs)
      reactive to certain conserved self-antigens (citrate synthase (A-CIT),
      chondroitin sulphate C (A-COS) and 60 kDa heat shock proteins (A-HSP) in the sera
      of 78 healthy individuals and in their 86 children. In case of all the 164
      individuals alleles of several polymorphisms were determined in class II (HLA-DQ,
      -DR), class III (AGER-429T>C, HSP70-2 1267A>G, TNF-308G>A, CFB S/F, copy number
      of the C4A and C4B genes), and class I (HLA-A, -B) regions of the major
      histocompatibility complex (MHC). Since the samples originated from a family
      study, extended MHC haplotypes were also determined for each study participant.
      Our results show that children of parents with low NAAb concentration have
      significantly lower serum concentrations of all the three NAAbs, as compared to
      offsprings of parents without reduced serum concentration. This indicates that
      the serum levels of these NAAbs were partly regulated by factors which are
      inherited from the parents to offsprings. In further studies performed only in
      genetically independent parents, we found significant differences in the serum
      levels of the IgM type A-CIT and A-COS antibodies (Abs) between carriers and non
      carriers of the HLA-DR2 (15 and 16) antigens. In both cases the Ab concentrations
      were higher in the HLA-DR15 carriers (p=0.002 and p=0.008, respectively) and
      lower in DR16 carriers (p=0.029 and p=0.049, respectively) than in the non
      carriers. Even more significant differences were found when the levels of two Abs
      were evaluated together. Frequency of the DR15 carriers was significantly lower
      among subjects with one or two low (in the lowest quartile) titers of A-CIT/A-COS
      Abs (p=0.014), A-CIT/A-HSP Abs (p=0.016) and A-COS/A-HSP Abs (p=0.013) as
      compared to those with normal Ab titers for both antigens. By contrast, frequency
      of the DR16 carriers was significantly higher among subjects with one or two low
      A-CIT/A-COS Abs (p=0.001), A-CIT/A-HSP Abs (p=0.002) and A-COS/A-HSP Abs
      (p=0.021) as compared to those with normal Ab titers for both antigens. Similar
      differences were found for both IgM type antibodies when carriers and non
      carriers of the HLA-DR15-DQ6 and HLA-DR16-DQ5 haplotypes were considered. These
      novel observations indicate that not only adaptive immune response but also
      natural autoantibody pattern, as a part of innate immune response, is influenced
      by the MHC allele composition.

PMID- 19167761
TI  - HLA-B27 polymorphism at position 116 critically influences the association with
      TAP/tapasin, intracellular trafficking and conformational homodimers formation.
AB  - HLA-B27 confers susceptibility to ankylosing spondylitis but AS disease
      mechanisms remain unknown. We determined here the effect of polymorphism and
      tapasin dependence on the expression, intracellular maturation and homodimer
      formation among HLA-B27 subtypes. We found that B*2709 with a histidine at
      position 116 was strongly associated with the transporter associated with antigen
      processing complex, correlated with lower, non-conformational expression on the
      cell surface, delayed maturation rate and minimal conformational and non
      conformational homodimer formation. In contrast, B*2705 showed a low dependence
      for transporter associated with antigen processing, faster intracellular
      maturation and increased levels of homodimeric forms. The absence of tapasin
      significantly influenced the rate of intracellular maturation of B*2709, showing
      faster transport out of the endoplasmic reticulum, but similar to that of B*2705.
      All B27 subtypes examined were unable to express conformational homodimeric forms
      in the absence of tapasin. This study suggests that HLA-B27 polymorphism drives
      the tapasin dependency, rates of intracellular maturation and expressions of
      homodimers.

PMID- 19167762
TI  - Sampling methods to detect carriage of Neisseria meningitidis; literature review.
AB  - OBJECTIVES: Studies of meningococcal carriage are important in understanding the
      epidemiology of meningococcal disease and the impact of vaccination programmes.
      However, microbiological sampling methods to determine pharyngeal carriage are
      not consistent between studies and the optimal method is uncertain. METHODS: A
      comprehensive literature search was undertaken using Medline, Embase and the
      Cochrane Library (Feb 2008) to identify studies comparing isolation rates using
      different sampling methods. RESULTS: Four studies compared isolation of
      meningococci from different pharyngeal sites. Nasopharyngeal swabs taken through
      the nose were less likely to yield meningococcal cultures than pharyngeal swabs
      taken through the mouth. One study investigated different sampling sites using
      swabs taken through the mouth and found higher yields from the posterior
      pharyngeal wall compared to the tonsils (32.2% cf 19.4%, p=0.001). Four studies
      compared the yield obtained using transport medium to direct plating. Loss of
      yield in transport medium ranged from 5.7% to 16.4% after storage for >5h.
      CONCLUSIONS: The evidence to date suggests that meningococcal carriage should be
      assessed by swabbing the posterior pharyngeal wall through the mouth, and that
      swabs should be plated directly on site or placed in transport medium for <5h.
      SUMMARY: The current literature suggests meningococcal carriage is best assessed
      by swabbing the posterior pharyngeal wall through the mouth with direct plating
      or keeping transport time to below 5h. Whether a swab taken from both the
      posterior pharynx and the tonsils improves yield further needs evaluation.

PMID- 19167760
TI  - C3a receptor deficiency accelerates the onset of renal injury in the MRL/lpr
      mouse.
AB  - The development and progression of systemic lupus erythematosus (SLE) is strongly
      associated with complement activation and deposition. The anaphylatoxin C3a is a
      product of complement activation with immunomodulatory properties, and the
      receptor for C3a (C3aR) is not only expressed by granulocytes and antigen
      presenting cell populations, but it is also strongly up-regulated in lupus prone
      mice with active nephritis. In order to characterize the role of the C3aR in
      inflammatory nephritis, we bred C3aR knock out mice onto the MRL/lpr genetic
      background (C3aR KO MRL). Compared to control MRL/lpr mice, C3aR KO MRL mice had
      elevated auto-antibody titers and an earlier onset of renal injury. At 8 weeks,
      renal expression of a wide range of chemokines and chemokine receptors was
      increased in C3aR KO MRL kidneys compared to controls. Only the expression of MCP
      1 was significantly decreased in the C3aR KO MRL mice. The increased chemokine
      and chemokine receptor expression seen in the C3aR KO MRL mice was associated
      with a more rapid rise in serum creatinine and the acceleration of renal
      fibrosis. However, loss of the C3aR had little impact on long-term kidney injury
      and did not alter survival. These findings suggest that activation of the C3aR
      plays a protective, not pathologic, role in the early phase of inflammatory
      nephritis in the MRL/lpr model of SLE.

PMID- 19167763
TI  - Surgery for otitis media and infectious susceptibility in 10-year old school
      children.
AB  - OBJECTIVES: Assess infectious susceptibility in children previously operated for
      otitis media and evaluate reliability of parental reported otitis media surgery
      in the same group of children. METHODS: Population based, cross-sectional survey
      of 10-year olds in the city of Oslo, Norway studying otitis media and surgical
      intervention in n=3406 with reliability assessments in a subset of n=2027.
      RESULTS: Ten percent of children had otitis media surgery. Peak age was 2.5 years
      for adenoidectomy and tympanostomy tubes and 3 years for myringotomy. The crude
      odds ratio (cOR) with 95% confidence interval (95% CI) for one or more episodes
      of otitis media at 10 years in children with previous otitis media surgery was
      3.4 (2.7-4.4). Intervention after the child was 4 years increased the risk
      further, crude odds ratio 4.2 (2.9-6.1). Kappa coefficients for agreement in
      answers to questions on otitis media surgery performed in children between 0 and
      4 years were 0.9 for adenoidectomy, 1.0 for tympanostomy tubes, and 0.6 for
      myringotomy. CONCLUSION: Otitis media in 10-year old children was associated with
      previous surgical intervention, particularly when performed after 4 years of age.
      Parental reports of tympanostomy tubes and adenoidectomy in early childhood were
      found reliable.

PMID- 19167764
TI  - Intractable supraventricular tachycardia as first presentation of thoracic aortic
      dissection: case report.
AB  - A patient presented with palpitations at the emergency department 3 days after a
      percutaneous coronary intervention complicated by dissection of the left anterior
      descending and circumflex coronary arteries. Physical examination revealed a high
      pulse rate and low blood pressure and the electrocardiogram demonstrated
      atrioventricular nodal re-entry tachycardia. This arrhythmia was eventually
      terminated by electrical cardioversion. Echocardiography demonstrated moderate
      aortic regurgitation and subsequent computed tomography showed a large Stanford
      type A aortic dissection. The patient was successfully operated and discharged 10
      days after surgery.

PMID- 19167765
TI  - Creation of a functional tricuspid valve: novel use of percutaneously implanted
      valve in right atrial to right ventricular conduit in a patient with tricuspid
      atresia.
AB  - We report the first use of a stented pulmonic valve within the right atrial to
      right ventricular conduit of a patient who underwent a Bjork modification Fontan
      for tricuspid atresia. In effect, a functional tricuspid valve was created. This
      case report demonstrates the feasibility of transcatheter valve replacement in
      positions other than the pulmonic or aortic valve and that future revision of
      conduits in the Bjork modification Fontan can be performed percutaneously.

PMID- 19167766
TI  - Effect of L-arginine on circulating endothelial progenitor cells in
      hypercholesterolemic rabbits.
AB  - The cardiovascular disease risk factors result in endothelial cells apoptosis and
      injury. Recently, endothelial progenitor cells (EPCs) have been shown to
      participate in ongoing endothelial repair. Nitric Oxide (NO) is essential for
      mobilization and functional activity of EPCs. We hypothesized that L-arginine (NO
      precursor) supplementation may increase EPCs number in hypercholesterolemic
      rabbits. EPCs, plasma levels of nitrite, von Willebrand Factor (vWF) and Intima
      Media thickness ratio were determined in rabbits feeding high-cholesterol diet or
      high-cholesterol diet with L-arginine(3% in drinking water). L-arginine
      supplementation had a significant effect on the nitrite levels, and EPC numbers,
      and inhibited vWF increment and atherosclerosis progression (p<0.05). Our results
      suggest that the beneficial effect of L-arginine in prevention of atherosclerosis
      may be due to the modulation of EPC levels.

PMID- 19167768
TI  - Inadequate consultation behavior modulates the relationship between type D
      personality and impaired health status in chronic heart failure.
AB  - BACKGROUND: Psychological risk factors for impaired health outcomes have been
      acknowledged in chronic heart failure (CHF), with Type D personality being such a
      risk factor. Inadequate consultation behavior, a specific aspect of self
      management, might be one mechanism in explaining the adverse effect of Type D on
      health outcomes. In this study we examined the relationship between Type D
      personality, impaired disease-specific health status, and inadequate consultation
      behavior. METHODS AND RESULTS: CHF outpatients (n=313) completed the Type D Scale
      (DS14) at baseline, and the European Heart Failure Self-care Behaviour Scale
      (EHFScBS) and the Minnesota Living with Heart Failure Questionnaire (MLWHFQ) at 6
      month follow-up. Type D personality independently predicted inadequate
      consultation behavior (OR=1.80, 95%CI [1.03-3.16], p=.04) and impaired health
      status (OR=3.61, 95%CI [1.93-6.74], p<.001) at 6-month follow-up, adjusting for
      demographic and clinical variables. Inadequate consultation behavior (OR=1.80,
      95%CI [1.11-2.94], p=.02) and NYHA-class (OR=2.83, 95%CI [1.17-4.71], p<.001)
      were associated with impaired health status, after controlling for demographics,
      clinical variables, and Type D personality. Post-hoc multivariable analysis
      pointed out that Type D patients who displayed inadequate consultation behavior
      were at a 6-fold increased risk of reporting impaired health status, compared to
      the reference group of non-Type D patients who displayed adequate consultation
      behavior (OR=6.06, 95%CI [2.53-14.52], p<.001). CONCLUSIONS: These findings
      provide evidence for inadequate behavior as a mechanism that may explain the link
      between Type D personality and impaired health status. Future studies are
      warranted to elaborate on these findings.

PMID- 19167767
TI  - Temporal and spatial distribution of ST-elevation myocardial infarction
      admissions in a countrywide registry.
AB  - BACKGROUND: Current guidelines propose different reperfusion strategies for ST
      elevation myocardial infarction (STEMI) depending on the time delay from pain
      onset, the availability of a catheterization laboratory and the patient's
      characteristics. In order to implement national strategies to improve reperfusion
      rates the existing situation must be first analysed. The aim of this report is to
      provide a description of where and when STEMI patients present in a countrywide
      registry. METHODS: The Hellenic Infarction Observation Study (HELIOS) was a
      countrywide registry that enrolled 1096 patients with STEMI from 31 hospitals
      with a proportional representation of all types of hospitals from all
      geographical areas. We recorded the proportion of patients that fits within each
      category of treatment algorithms. RESULTS: The following percentages of the total
      STEMI population were recorded: a) admitted in invasive hospitals within 12 h
      28.7% (with 26% of those not reperfused) and after 12 h 5.9% and b) admitted in
      non-invasive hospitals within 3 h 34.9% (with 30% of those not reperfused), 3-12
      h 19.3% and after 12 h 11%. CONCLUSIONS: A large proportion of STEMI patients are
      admitted either in an invasive hospital within 12 h or in a non-invasive one
      within 3 h from pain onset and therefore can be treated locally according to the
      guidelines. A relatively small percentage of patients are late presenters in non
      invasive centres and are candidates for immediate transfer for primary PCI. These
      data could be useful in planning reperfusion strategies at countrywide level
      since not all patients may require immediate transfer for primary PCI.

PMID- 19167769
TI  - Low invasive angiogenic therapy for myocardial infarction by retrograde
      transplantation of mononuclear cells expressing the VEGF gene.
AB  - BACKGROUND: Although transplantation of mononuclear cells (MNCs) induces
      angiogenesis in myocardial infarction, transplantation requires a large amount of
      bone marrow or peripheral blood cells. We examined the effects of transplantation
      of peripheral MNCs expressing an exogenous vascular endothelial growth factor
      (VEGF) gene in a pig model of acute myocardial infarction (AMI). METHODS: MNCs
      were isolated from 20 ml peripheral blood from pigs and transfected with 10
      microg of human VEGF165 plasmid (phVEGF). Myocardial infarction was induced by
      occlusion of the mid portion of the left anterior descending coronary artery
      (LAD) in anesthetized pigs. At 4 h after total occlusion, 5 x 10(6) VEGF
      transfected MNCs were retrogradely transplanted into the pig via the coronary
      vein. Cardiac function, neovascularization and histology of the ischemic tissue
      were evaluated 4 weeks after transplantation. RESULTS: MNCs expressing hVEGF and
      infused via the coronary vein were efficiently delivered the heart in pigs with
      myocardial infarction. Transplantation of MNCs expressing hVEGF significantly
      increased left ventricular (LV) function, collateral vessels, and capillary
      density in heart from AMI model pigs. Transplantation of MNCs expressing hVEGF
      increased the wall thickness of the scar in the heart after AMI. CONCLUSIONS:
      Retrograde transplantation of peripheral blood MNCs expressing hVEGF efficiently
      induced angiogenesis and improved the impaired LV function in hearts of pigs with
      AMI. These findings indicate that angiogenic cells and gene therapy may be useful
      to treat ischemic heart disease.

PMID- 19167770
TI  - The Glass Menagerie: diatoms for novel applications in nanotechnology.
AB  - Diatoms are unicellular, eukaryotic, photosynthetic algae that are found in
      aquatic environments. Diatoms have enormous ecological importance on this planet
      and display a diversity of patterns and structures at the nano- to millimetre
      scale. Diatom nanotechnology, a new interdisciplinary area, has spawned
      collaborations in biology, biochemistry, biotechnology, physics, chemistry,
      material science and engineering. We survey diatom nanotechnology since 2005,
      emphasizing recent advances in diatom biomineralization, biophotonics,
      photoluminescence, microfluidics, compustat domestication, multiscale porosity,
      silica sequestering of proteins, detection of trace gases, controlled drug
      delivery and computer design. Diatoms might become the first organisms for which
      the gap in our knowledge of the relationship between genotype and phenotype is
      closed.

PMID- 19167771
TI  - Two-tier analysis of histone H2AX phosphorylation allows the identification of
      Ataxia Telangiectasia heterozygotes.
AB  - BACKGROUND AND PURPOSE: Ataxia Telangiectasia (A-T) heterozygotes constitute 0.36
      1% of the general population. They have a higher risk of developing several types
      of cancer and may be more likely to suffer side-effects following radiotherapy
      than the general population. Their identification is both labor- and time
      consuming and the sensitivity and specificity of the methods employed has not
      been evaluated. This paper describes a new approach to the identification of A-T
      heterozygotes based on a two-tier analysis of histone H2AX phosphorylation.
      MATERIALS AND METHODS: We compared the T-cell phenotype after exposure to 2 Gy in
      nine obligate A-T heterozygotes and 17 normal donors. Examined end points were
      histone H2AX phosphorylation by flow cytometry 1 h after irradiation (kinase
      proficiency) and the residual gamma-H2AX foci by confocal microscopy 72 h after
      irradiation (DSB repair proficiency). RESULTS: The sequential use of these two
      methods results in 100% positive predictive value (PPV), 67% negative predictive
      value (NPV), 78% sensitivity, and 100% specificity. The overall hit rate, i.e.
      the ratio between the true positives plus the true negatives and the total number
      of observations was 85%. CONCLUSIONS: A-T heterozygotes can be identified by
      analysing irradiated T-cell H2AX phosphorylation level and residual gamma-H2AX
      foci.

PMID- 19167772
TI  - Inactivation of Escherichia coli and Listeria innocua in apple and carrot juices
      using high pressure homogenization and nisin.
AB  - High pressure homogenization has been of growing interest as a nonthermal
      technology for the inactivation of microorganisms in fruit and vegetable juices.
      Cells of Escherichia coli and Listeria innocua, used as surrogates for foodborne
      pathogens, were inoculated into apple or carrot juice (approximately 7 log(10)
      CFU/ml) containing 0 or 10 IU/ml nisin and subjected to 350 to 0 MPa high
      pressure homogenization. At 50 MPa homogenization pressure intervals, juice
      samples were collected, immediately cooled to <10 degrees C, and then serially
      diluted and plated on nonselective recovery media. Following incubation,
      survivors were enumerated. As processing pressure increased, inactivation of E.
      coli increased, and a >5 log reduction of cells was achieved following exposure
      to pressures in excess >250 MPa. In contrast, little inactivation was observed
      for L. innocua with pressure <250 MPa and up to 350 MPa processing pressure was
      required to achieve an equivalent 5 log inactivation. The addition of 10 IU
      nisin, together with high pressure homogenization, did not exhibit significant
      additional E. coli inactivation, but interactions were observed with L. innocua.
      Results indicate that high pressure homogenization processing is a promising
      technology to achieve pathogen decontamination in fruit and vegetable juices.

PMID- 19167773
TI  - Impaired left ventricular systolic and diastolic function in patients with
      metabolic syndrome as assessed by strain and strain rate imaging.
AB  - The present study aimed to investigate cardiac structural and functional
      alterations in patients with metabolic syndrome (MS) and to compare those with
      control subjects. Strain and strain rate (SR) imaging were preformed in 200
      patients with MS and 197 normal subjects. The patients were further divided into
      Group 1 (with three metabolic disorders) and Group 2 (with four metabolic
      disorders) to elucidate the influence of different metabolic components on left
      ventricular (LV) functions. LV diastolic and systolic functions were determined
      by the mean systolic strain, SR-LVs and SR-LVe. There were no differences in LVEF
      among the three groups. However, the mean systolic strain, SR-LVs and SR-LVe,
      were significantly decreased in Group 1 and Group2 when compared with control
      subjects (all P<0.001). The mean systolic strain and SR-LVe were lower in Group 2
      than Group 1 (all P<0.05). Stepwise multiple regression analyses revealed that
      the W-H ratio was an independent predictor of the LV systolic function, whereas W
      H ratio, HDL cholesterol and SBP were independent predictors of LV diastolic
      function. In summary, our results demonstrated that LV systolic and diastolic
      functions were impaired in patients with metabolic syndrome even if they have
      normal LVEF. Strain and SR imaging would be a sensitive and feasible method to
      detect subclinical abnormalities in those populations.

PMID- 19167774
TI  - Impact of glucose metabolism and birth size on cognitive performance in elderly
      subjects.
AB  - AIMS: We aimed to investigate the impact of diabetes and impaired glucose
      tolerance on cognitive performance and to explore the association between birth
      weight and cognitive performance among diabetic subjects. METHODS: We performed a
      standard oral glucose tolerance test and a computerised test for assessment of
      cognitive performance (CogState) in 1243 subjects; 173 of them had type 2
      diabetes. At the time of cognitive testing the mean age of the subjects was 64
      years. Subjects with type 1 diabetes or a history of stroke were excluded.
      RESULTS: Subjects with known diabetes performed significantly poorer in cognitive
      tasks measuring visual attention, working memory and episodic learning than
      subjects with normal glucose tolerance. Subjects with newly diagnosed diabetes or
      milder impairments in glucose regulation did not differ from the normoglycaemic
      group. A low birth weight enhanced the association between diabetes and poor
      performance in the working memory and episodic learning tasks. CONCLUSIONS:
      Poorer cognitive performance was associated with known type 2 diabetes but not
      with newly diagnosed diabetes or milder impairments in glucose regulation. Low
      birth weight was found to be an additional vulnerability factor enhancing
      cognitive decline in diabetic subjects.

PMID- 19167775
TI  - Toxoplasma PRP1 is an ortholog of parafusin (PFUS) in vesicle scaffold assembly
      in Ca(2+)-regulated exocytosis.
AB  - The Paramecium tetraurelia protein parafusin (PFUS) and the Toxoplasma gondii
      protein parafusin-related protein 1 (PRP1) both have two covalent modifications
      (phosphorylation and phosphoglucosylation) and both are members of the
      phosphoglucomutase superfamily, associating with secretory vesicle scaffolds in
      their respective cells. This study tests the hypothesis that PRP1 is a functional
      ortholog of PFUS, functioning identically in Ca(2+)-regulated exocytosis.
      Electroporation of fluorescently labeled recombinant His-PRP1 into live
      Paramecium cells resulted in its localization to docked, dense-core secretory
      vesicles (DCSVs) in a pattern identical to endogenous PFUS. In tam8 mutants,
      defective in transport of DCSVs, the fluorescently labeled protein was restricted
      to the un-transported DCSVs. Specificity of PRP1 localization was demonstrated by
      electroporating labeled actin or pyruvate kinase, which both failed to localize
      to either docked or undocked vesicles. In wild-type Paramecium, electroporated
      His-PRP1 dissociated from DCSVs upon exocytosis, and re-associated as new
      organelles formed. Mutagenized His-PRP1 species (S146A or S146E) cannot be
      phosphorylated by P2 calcium-dependent kinase in vitro. Upon electroporation,
      these molecules remained cytoplasmic and un-associated with DCSVs, while mutation
      of another PRP1 serine residue (S560A) did neither affect the localization to the
      DCSVs nor the phosphorylation pattern. Therefore, in this heterologous system,
      localization, transport and dissociation/re-association of PRP1 substituted for
      PFUS, supporting the conclusion that the proteins are functional orthologs. The
      assay also identified a strategic residue S146 within the PFUS ortholog (S138 in
      PFUS by extrapolation) required for post-translational modification, DCSV
      scaffold association and for exocytosis.

PMID- 19167776
TI  - Expression of a functional epidermal growth factor receptor on human adipose
      derived mesenchymal stem cells and its signaling mechanism.
AB  - Adult stem cells act as a pluripotent source of regenerative cells during tissue
      injury. Despite expanded research in stem cell biology, understanding how growth
      and migration of adipose-derived adult mesenchymal stem cells (ASC) are governed
      by interactions with growth factors is very limited. One important property of
      ASC is the presence of the epidermal growth factor (EGF) receptor and the
      cellular response to soluble EGF. Expression of the EGF receptor was proven by
      PCR and Western blotting. Signal transduction was analyzed by Western blotting
      and PhosFlow assay. EGF caused robust phosphorylation of SHC and ERK1/2, which
      could be inhibited by EGF receptor antagonist AG1478 and MEK inhibitor PD98059.
      ASC proliferation was determined by MTT assay. Stem cell migration was analyzed
      in a modified Boyden chamber. Incubation with EGF led to cell proliferation and
      induced cell migration, but did not change the undifferentiated state of the
      cells. In the kidney, injured renal tubular cells express high amounts of EGF.
      Therefore, our results may highlight a mechanism underlying renal regeneration.
      Thus, future in vivo studies that focus on the effects of EGF on recruitment of
      ASC to sites of injury are necessary.

PMID- 19167777
TI  - Yeast heat-shock protein gene HSP26 enhances freezing tolerance in Arabidopsis.
AB  - In the yeast Saccharomyces cerevisiae, the molecular chaperone Hsp26 is one
      component of the heat-shock response. Hsp26 has the remarkable ability to
      directly sense increases in temperature and switch from an inactive state to a
      chaperone-active state. In this study, we report a functional analysis of Hsp26
      in Arabidopsis thaliana and its response to freezing stress. After freezing
      stress, the HSP26 transgenic plants exhibited stronger growth than the wild-type
      plants. We found that over-expression of HSP26 in Arabidopsis increased the
      amounts of free proline and soluble sugars, elevated the expression of stress
      defense genes, and enhanced Arabidopsis tolerance to freezing stress. Taken
      together, our results indicate that Hsp26 may play an important role in the
      response of transgenic Arabidopsis plants to freezing stresses.

PMID- 19167778
TI  - Salt-inducible isoform of plasma membrane H+ATPase gene in rice remains
      constitutively expressed in natural halophyte, Suaeda maritima.
AB  - To look into a possible involvement of plasma membrane H+ATPase (PM-H+ATPase, EC
      3.6.3.6) in mitigation of physiological disturbances imposed by salt stress,
      response of the enzyme was studied in two Oryza sativa Indica cultivars, salt
      tolerant Lunishri and non-tolerant Badami, and a natural halophyte Suaeda
      maritima after challenge of the young plants with NaCl. Significant increase in
      activity of the enzyme was observed in response to NaCl in all the test plants
      with S. maritima showing maximum increase. Protein blot analysis, however, did
      not show any increase in the amount of the enzyme (protein). RNA blot analysis,
      on the other hand, revealed significant increase in transcript level of the
      enzyme upon NaCl treatment. In the rice cultivars, salt treatment also induced
      expression of a new isoform of PM-H+ATPase gene, not reported so far. The induced
      transcript showed maximum homology to OSA7 (O. sativa PM-H+ATPase isoform 7).
      Similar transcript message, however, remained constitutively present in S.
      maritima, along with the transcript of another isoform of PM-H+ATPase showing
      resemblance to OSA3 (O. sativa PM-H+ATPase isoform 3). The latter was the only PM
      H+ATPase isoform expressed in both the rice cultivars not exposed to NaCl. In the
      salt-treated test plants, both rice and S. maritima, the salt-inducible PM
      H+ATPase isoform resembling OSA7 was expressed in much greater amount than that
      resembling OSA3. Appearance of a new PM-H+ATPase transcript, besides increase in
      the enzyme activity, indicates the important role of the enzyme in maintaining
      ion-homeostasis in plants under salt stress, enabling them to survive under
      saline conditions.

PMID- 19167779
TI  - Nickel allergy in the United States: a public health issue in need of a "nickel
      directive".

PMID- 19167780
TI  - Psoriatic arthritis is a strong predictor of sleep interference in patients with
      psoriasis.
AB  - OBJECTIVE: We sought to determine what clinical features of psoriasis predict
      sleep interference. METHODS: Data were obtained from 420 respondents to the 2005
      National Psoriasis Foundation telephone and e-mail surveys. Logistic regression
      was used to determine whether disease severity, body mass index, age of onset,
      psoriatic arthritis, income, ethnicity, sex, current therapy, and quality-of-life
      measures predicted reported sleep interference within the last month. RESULTS:
      Psoriatic arthritis was the most significant predictor of sleep disturbance (odds
      ratio = 3.26). Itch, pain of lesions, and impact on emotional well-being were
      also significant predictors (odds ratio 1.26, 1.22, and 1.18, respectively). Body
      surface area covered with psoriasis, body mass index, and therapy were not
      significant predictors of sleep interference. LIMITATIONS: All data were self
      reported and not physician-assessed. CONCLUSIONS: History of psoriatic arthritis,
      presence of itch and pain of psoriatic lesions, and impact of psoriasis on
      overall emotional well-being predict sleep interference.

PMID- 19167781
TI  - Physiologic changes in vascular birthmarks during early infancy: Mechanisms and
      clinical implications.
AB  - Vascular birthmarks are the most common birthmarks encountered in newborns. Many
      dermatologists are unfamiliar with the normal physiologic changes that affect and
      alter their appearance during early infancy. In this article we discuss normal
      newborn hemodynamic/neurovascular physiology and the associated clinical findings
      in neonatal skin. The physiologic anemia of infancy and its resultant effects on
      skin color and the appearance of vascular birthmarks are detailed. Finally, the
      pitfalls and obstacles to early diagnosis of vascular birthmarks and the subtle
      differences between them are reviewed, as are the challenges in assessing
      response to early pulsed dye laser treatment in the context of the changing
      vascular physiology.

PMID- 19167782
TI  - Neurocognitive function of emergency department patients with mild traumatic
      brain injury.
AB  - STUDY OBJECTIVE: We characterize the neurocognitive function of patients
      presenting to the emergency department (ED) with mild traumatic brain injury.
      METHODS: This prospective study took place at an urban, academic ED and Level I
      trauma center. Case patients consisted of a convenience sample of ED patients
      aged 18 to 59 years, presenting to the ED with mild traumatic brain injury and
      having a head computed tomography scan without traumatic abnormalities. Controls
      consisted of patients aged 18 to 59 years, presenting to the ED with an isolated,
      nondominant hand extremity injury. We excluded patients with multiple injuries
      and recent alcohol consumption. Subjects completed a computerized neurocognitive
      test battery (Immediate Post-concussion Assessment and Cognitive Testing). The
      primary measures were verbal memory, visual memory, and visual motor and reaction
      speed. We compared raw and age-normalized neurocognitive performance between case
      patients and controls by using nonparametric statistics. RESULTS: We included a
      total of 23 head-injured case patients and 31 non-head-injured controls. Case
      patients and controls exhibited similar raw (median 80.1 versus 85.0 points;
      difference in medians -4.9; P=.26) and age-normalized (31.9 versus 57.4
      percentile; difference in medians -25.5; P=.12) verbal memory. Case patients and
      controls exhibited similar raw (64.6 versus 63.5; difference 1.1; P=.79) and age
      normalized (20.8 versus 25.8 percentile; difference -5.0; P=.44) visual memory.
      Compared with controls, mild traumatic brain injury case patients demonstrated
      slower raw (31.6 versus 37.0 points; difference -5.4; P=.002) and age-normalized
      (17.1 versus 57.6 percentile; difference -40.5; P=.001) visual motor speed. Mild
      traumatic brain injury case patients exhibited slower raw (median 0.66 versus
      0.60 seconds; difference 0.06; P=.01) and age-normalized (29.3 versus 42.8
      percentile; difference -13.5; P=.009) reaction times. CONCLUSION: In conclusion,
      compared with the non-head-injured patients, ED mild traumatic brain injury
      patients demonstrated subtle but discernible neurocognitive deficits.

PMID- 19167783
TI  - Effect of transport interval on out-of-hospital cardiac arrest survival in the
      OPALS study: implications for triaging patients to specialized cardiac arrest
      centers.
AB  - STUDY OBJECTIVE: To identify any association between out-of-hospital transport
      interval and survival to hospital discharge in victims of out-of-hospital cardiac
      arrest. METHODS: Data from the Ontario Prehospital Advanced Life Support Study
      (January 1, 1991, to December 31, 2002), an Utstein-compliant registry of out-of
      hospital cardiac arrest patients from 21 communities, were analyzed. Logistic
      regression identified factors that were independently associated with survival in
      consecutive adult, nontraumatic, out-of-hospital cardiac arrest patients and in
      the subgroup with return of spontaneous circulation. RESULTS: A total of 18,987
      patients met criteria and 15,559 (81.9%) had complete data for analysis (study
      group). Return of spontaneous circulation was achieved in 2,299 patients (14.8%),
      and 689 (4.4%) survived to hospital discharge. Median transport interval was 4.0
      minutes (25th quartile 3.0 minutes; 75th quartile 6.2 minutes) for survivors and
      4.2 minutes (25th quartile 3.0, 75th quartile 6.2) for nonsurvivors. Logistic
      regression revealed multiple factors that were independently associated with
      survival: witnessed arrest (odds ratio 2.61; 95% confidence interval [CI] 2.05 to
      3.34), bystander cardiopulmonary resuscitation (odds ratio 2.22; 95% CI 1.82 to
      2.70), initial rhythm of ventricular fibrillation/tachycardia (odds ratio 2.22;
      95% CI 1.97 to 2.50), and shorter emergency medical services (EMS) response
      interval (odds ratio 1.26; 95% CI 1.20 to 1.33). There was no association between
      transport interval and survival in either the study group (odds ratio 1.01; 95%
      CI 0.99 to 1.05) or the return of spontaneous circulation subgroup (odds ratio
      1.04; 95% CI 0.99, 1.08). CONCLUSION: In a large out-of-hospital cardiac arrest
      study from demographically diverse EMS systems, longer transport interval was not
      associated with decreased survival. Given the growing evidence showing major
      influence from specialized postarrest care, these findings support conducting
      clinical trials that assess the effectiveness and safety of bypassing local
      hospitals to take patients to regional cardiac arrest centers.

PMID- 19167785
TI  - Evidence-based Emergency Medicine/Systematic Review Abstract. Rhythm control with
      electrocardioversion for atrial fibrillation and flutter.

PMID- 19167786
TI  - Bedside sonographic measurement of optic nerve sheath diameter as a predictor of
      increased intracranial pressure in children.
AB  - STUDY OBJECTIVE: We investigate the test performance of emergency physician
      performed sonographic measurement of optic nerve sheath diameter for diagnosis of
      increased intracranial pressure. METHODS: Children between the ages of 0 and 18
      years with suspected increased intracranial pressure were prospectively recruited
      from the emergency department and ICU of an urban, tertiary-level, freestanding
      pediatric facility. Pediatric emergency physicians with goal-directed training in
      ophthalmic sonography measured optic nerve sheath diameter. Images were recorded
      and subsequently reviewed by a pediatric ophthalmologist and an ophthalmic
      sonographer, both of whom were blind to the patient's clinical condition.
      Measurements obtained by the ophthalmic sonographer were considered the criterion
      standard. An optic nerve sheath diameter greater than 4.0 mm in subjects younger
      than 1 year and greater than 4.5 mm in older children was considered abnormal.
      The diagnosis of increased intracranial pressure was based on results of cranial
      imaging or direct measurement of intracranial pressure. RESULTS: Sixty-four
      patients were recruited, of whom 24 (37%) had a confirmed diagnosis of increased
      intracranial pressure. The sensitivity of optic nerve sheath diameter as a
      screening test for increased intracranial pressure was 83% (95% confidence
      interval [CI] 0.60 to 0.94); specificity was 38% (95% CI 0.23 to 0.54); positive
      likelihood ratio was 1.32 (95% CI 0.97 to 1.79) and negative likelihood ratio was
      0.46 (95% CI 0.18 to 1.23). There was fair to good interobserver agreement
      between the pediatric emergency physician and ophthalmic sonographer (kappa 0.52)
      and pediatric ophthalmologist (kappa 0.64). CONCLUSION: The sensitivity and
      specificity of bedside sonographic measurement of optic nerve sheath diameter is
      inadequate to aid medical decisionmaking in children with suspected increased
      intracranial pressure. Pediatric emergency physicians with focused training by a
      pediatric ophthalmologist familiar with ophthalmic sonography can measure optic
      nerve sheath diameter accurately.

PMID- 19167787
TI  - Juglone derivatives as antitubercular agents: a rationale for the activity
      profile.
AB  - The antitubercular activity and cytotoxicity of juglone derivatives were analyzed
      with the topological and molecular surface features from a web-based server,
      MODEL (MOlecular DEscriptor Lab). Analysis of the structural features in
      conjunction with the biological endpoints in Combinatorial Protocol in Multiple
      Linear Regression led to the identification of seven descriptors for modeling the
      activity and six descriptors for that of the toxicity of the compounds. Analysis
      of these descriptors in PLS highlighted their relative significance in modulating
      the biological response. They suggested that structures with compact molecular
      arrangement, partial positive surface areas and increased autocorrelation with
      small lag values may lead to better antitubercular activity.

PMID- 19167788
TI  - The opinions of students of the first cycle of undergraduate pre-registration
      bridging nursing teaching programme at the Medical University of Lublin.
AB  - OBJECTIVES: Determination of the scope and character of the opinions of
      investigated students in the organizational and substantial dimension concerning
      bridging studies carried out in the first experimental cycle of this form of
      education in Poland. STUDY GROUP: The study covered 116 students of nursing
      supplementing their nursing vocational education to licentiate level. METHOD: The
      study was carried out by the method of diagnostic poll based on own version of
      questionnaire inquiry. Study results were assessed by a team of competent
      arbitrators in order to precisely determine their category, positive or negative
      opinions, and also subjected to statistical analysis using chi(2) test. RESULTS:
      Study results point to a greater number of positive than negative opinions
      pertaining to bridging education. The type of nursing or midwifery school
      completed and period of occupational experience, irrespective of its duration,
      positively correlated with the respondents' opinions on the sense of 'bridging
      education' and the choice of satisfying syllabus content.

PMID- 19167789
TI  - Video-based self-assessment: implementation and evaluation in an undergraduate
      nursing course.
AB  - This research was performed to investigate the effects of video-based self
      assessment on the ability of nursing students to accurately measure vital signs,
      their communication skills, and their satisfaction. This research was conducted
      between March 2007 and June 2007 as a quasi-experimental control-group, pretest
      posttest design. The study population was composed of 40 second-year student
      nurses who enrolled in a fundamentals of nursing course of a college of nursing,
      Ajou University in Korea. Results of the research indicate that there was a
      statistically significant difference in exam scores for assessing long-term
      memory video-review group demonstrating higher scores. Student satisfaction was
      also significantly higher in the video-review group than in the control group.
      These results may suggest video-based self-assessment is a beneficial and
      effective instructional method of training undergraduate nursing students to
      develop awareness of their strengths and weaknesses, and to improve their
      clinical and communication skills.

PMID- 19167790
TI  - Migration and bioavailability of (137)Cs in forest soil of southern Germany.
AB  - To give a quantitative description of the radiocaesium soil-plant transfer for
      fern (Dryopteris carthusiana) and blackberry (Rubus fruticosus), physical and
      chemical properties of soils in spruce and mixed forest stands were investigated.
      Of special interest was the selective sorption of radiocaesium, which was
      determined by measuring the Radiocaesium Interception Potential (RIP). Forest
      soil and plants were taken at 10 locations of the Altdorfer Wald (5 sites in
      spruce forest and 5 sites in mixed forest). It was found that the bioavailability
      of radiocaesium in spruce forest was on average seven times higher than in mixed
      forest. It was shown that important factors determining the bioavailability of
      radiocaesium in forest soil were its exchangeability and the radiocaesium
      interception potential (RIP) of the soil. Low potassium concentration in soil
      solution of forest soils favors radiocaesium soil-plant transfer. Ammonium in
      forest soils plays an even more important role than potassium as a mobilizer of
      radiocaesium. The availability factor - a function of RIP, exchangeability and
      cationic composition of soil solution - characterized reliably the soil-plant
      transfer in both spruce and mixed forest. For highly organic soils in coniferous
      forest, radiocaesium sorption at regular exchange sites should be taken into
      account when its bioavailability is considered.

PMID- 19167791
TI  - Merkel cell carcinoma of the alveolar mucosa in a young adult: a rare case
      report.
AB  - Merkel cell carcinoma (MCC) is an extremely rare and aggressive primary
      neuroendocrine neoplasm of the skin with a poor prognosis. It occurs mainly in
      the sixth and seventh decades of life and is usually associated with damage
      caused by over exposure to the sun. Its occurrence in intraoral mucosal sites is
      rare, and we know of only six reported cases. We report a rare case of MCC that
      arose in the alveolar mucosa of a young adult.

PMID- 19167792
TI  - Nitrous oxide emissions from an intensively managed greenhouse vegetable cropping
      system in Northern China.
AB  - Nitrous oxide (N(2)O) emissions from a typical greenhouse vegetable system in
      Northern China were measured from February 2004 to January 2006 using a close
      chamber method. Four nitrogen management levels (NN, MN, CN, and SN) were used.
      N(2)O emissions occurred intermittently in the growing season, strongly
      correlating with N fertilization and irrigation. No peak emissions were observed
      after fertilization in the late Autumn season due to low soil temperature. 57-94%
      of the seasonal N(2)O emissions came from the initial growth stage, corresponding
      to the rewetting process in the soil. The annual N(2)O emissions ranged from 2.6
      to 8.8 kg N ha(-1) yr(-1), accounting for 0.27-0.30% of the annual nitrogen
      input. Compared with conventional N management, site-specific N management
      reduced N fertilization rate by 69% in 2004 and by 76% in 2005, and consequently
      reduced N(2)O emissions by 51% in 2004 and 27% in 2005, respectively.

PMID- 19167793
TI  - Long-term pollution by chlordecone of tropical volcanic soils in the French West
      Indies: a simple leaching model accounts for current residue.
AB  - Chlordecone was applied between 1972 and 1993 in banana fields of the French West
      Indies. This resulted in long-term pollution of soils and contamination of
      waters, aquatic biota, and crops. To assess pollution level and duration
      according to soil type, WISORCH, a leaching model based on first-order desorption
      kinetics, was developed and run. Its input parameters are soil organic carbon
      content (SOC) and SOC/water partitioning coefficient (K(oc)). It accounts for
      current chlordecone soil contents and drainage water concentrations. The model
      was valid for andosol, which indicates that neither physico-chemical nor
      microbial degradation occurred. Dilution by previous deep tillages makes soil
      scrapping unrealistic. Lixiviation appeared the main way to reduce pollution.
      Besides the SOC and rainfall increases, K(oc) increased from nitisol to ferralsol
      and then andosol while lixiviation efficiency decreased. Consequently, pollution
      is bound to last for several decades for nitisol, centuries for ferralsol, and
      half a millennium for andosol.

PMID- 19167794
TI  - Occurrence and sources of polychlorinated dibenzo-p-dioxins, dibenzofurans and
      dioxin-like polychlorinated biphenyls in surficial sediments of Lakes Superior
      and Huron.
AB  - Concentrations and congener profile patterns of 2378-substituted PCDD/Fs and
      DLPCBs in offshore, nearshore and tributary sediments of Lakes Superior and Huron
      are reported, and spatial trends and source contributions assessed. PCDD/F
      concentrations ranged from 5 to 18,000 pg/g dw (Lake Superior) and 3 to 6100 pg/g
      dw (Lake Huron); DLPCBs ranged from 9 to 11,000 pg/g dw (Lake Superior) and 9 to
      27,000 pg/g dw (Lake Huron). Our analysis indicated atmospheric deposition is a
      primary source to depositional areas of both lakes; however, greater PCDD/F and
      DLPCB concentrations were observed at several nearshore and tributary sites, and
      were attributed to corresponding land use in the watershed. Statistical analysis
      and pattern comparison suggested that industrial inputs mainly associated with
      wood treatment plants, pulp and paper mills, mining operations, and chlorine
      based chemical manufacturing also contributed to contamination by PCDD/Fs and
      DLPCBs in certain nearshore and offshore areas of Lakes Superior and Huron.

PMID- 19167795
TI  - Environmental conditions enhance toxicant effects in larvae of the ground beetle
      Pterostichus oblongopunctatus (Coleoptera: Carabidae).
AB  - The wide geographical distribution of ground beetles Pterostichus
      oblongopunctatus makes them very likely to be exposed to several environmental
      stressors at the same time. These could include both climatic stress and exposure
      to chemicals. Our previous studies demonstrated that the combined effect of
      nickel (Ni) and chlorpyrifos (CHP) was temperature (T)-dependent in adult P.
      oblongopunctatus. Frequently the different developmental stages of an organism
      are differently sensitive to single stressors, and for a number of reasons, such
      as differences in exposure routes, their interactions may also take different
      forms. Because of this, we studied the effects of the same factors on the beetle
      larvae. The results showed that all factors, as well as their interactions,
      influenced larvae survival. The synergistic effect of Ni and CPF was temperature
      dependent and the effect of Ni x T interaction on the proportion of emerged
      imagines indicated stronger toxicity of Ni at 25 degrees C than at 10 degrees C.

PMID- 19167796
TI  - Caring for kidneys in the antipodes: how Australia and New Zealand have addressed
      the challenge of end-stage renal failure.
AB  - Clinicians in Australia and New Zealand have developed active programs for the
      treatment of patients with chronic renal disease, including end-stage renal
      failure. They became interested in treatment with dialysis and transplantation
      shortly after the initiation of these treatments elsewhere in the world and have
      distinguished themselves over the decades by striving to provide comprehensive
      treatment for all who appeared suitable on purely medical grounds, without
      patients' personal, financial, or social characteristics entering into
      consideration, and despite geographic and national economic impediments. They
      have undertaken all major forms of treatment promptly after the development of
      these internationally and have conducted significant research locally. Home
      hemodialysis and peritoneal dialysis have featured more prominently in their
      repertoire than has been the case in many other countries, whereas in
      transplantation, they have traditionally shown a strong interest in the sourcing
      of grafts from deceased donors. Their participation in the field of end-stage
      renal failure has benefited from long-standing institutional support not only at
      the level of the governments and legal systems of their 2 countries, but also
      through the collegiality generated by their active participation in many local
      and international scientific societies.

PMID- 19167797
TI  - The effects of dietary patterns on urinary albumin excretion: results of the
      Dietary Approaches to Stop Hypertension (DASH) Trial.
AB  - BACKGROUND: Dietary studies designed to decrease the urinary albumin excretion
      rate (AER) typically reduce protein by increasing lower protein plant foods and
      decreasing higher protein animal products. STUDY DESIGN: We evaluated AER while
      increasing protein intake in the Dietary Approaches to Stop Hypertension (DASH)
      Trial (randomized, parallel group, 8 week controlled feeding). SETTING &
      PARTICIPANTS: 378 individuals without diabetes with prehypertension or stage I
      hypertension. INTERVENTION: The DASH diet, 18% energy from protein, emphasizes,
      among other features, low-fat dairy products; and the fruit/vegetable (FV) and
      control diets, each with 15% energy from protein. OUTCOME: AER. MEASUREMENTS: We
      measured AER by using immunoassay and covariates at baseline and after 8 weeks.
      RESULTS: Baseline AER had a geometric mean value of 4.0 +/- 0.2 (SE) mg/24 h. In
      285 participants with baseline AER less than 7 mg/24 h, AER was unchanged by diet
      treatment (geometric mean, 2.5 +/- 0.2 mg/24 h in the control diet, 3.0 +/- 0.2
      mg/24 h in the FV diet, and 2.8 +/- 0.2 mg/24 h in the DASH diet). Conversely, in
      93 participants with baseline AER of 7 mg/24 h or greater, end-of-feeding AER was
      lower in the FV diet (6.6 +/- 1.0 mg/24 h) than in the control (11.4 +/- 1.8
      mg/24 h; P = 0.01) or DASH diets (11.7 +/- 1.6 mg/24 h; P = 0.005). The DASH and
      control diets were not different (P = 0.9). LIMITATIONS: Long-term AER change not
      studied. CONCLUSIONS: The decrease in AER after 8 weeks occurred in only those
      with high-normal baseline AER in the FV diet, in a pattern distinct from the
      blood pressure decrease. The DASH diet did not increase AER despite a 3% increase
      in energy from protein.

PMID- 19167798
TI  - Serum fetuin a in hemodialysis: a link between derangement of calcium-phosphorus
      homeostasis and progression of atherosclerosis?
AB  - BACKGROUND: Fetuin A, a circulating inhibitor of ectopic calcification, is
      downregulated in hemodialysis and has been shown to predict cardiovascular
      mortality in this setting. The association of altered calcium-phosphorus with
      serum fetuin A levels is still a matter of debate. Although carotid intima-media
      thickness (cIMT) is a strong predictor of major cardiovascular events, its
      association with serum fetuin A levels is poorly defined. STUDY DESIGN: Cohort
      study. PARTICIPANTS & SETTINGS: 174 uremic patients on long-term hemodialysis
      therapy enrolled in 4 university hospitals. PREDICTORS: Serum fetuin A levels at
      the beginning of the study (T0) and after 12 months (T12). OUTCOMES: Progression
      of atherosclerosis assessed by means of cIMT measurements at 24 months (T24);
      cardiovascular morbidity and mortality at 36 months. RESULTS: Serum fetuin A
      concentrations at T0 and T12 were 282.3 +/- 79.4 and 290.0 +/- 92.2 microg/mL,
      respectively. Mean T0 and T24 cIMT values were 1.02 +/- 0.2 and 1.06 +/- 0.2 mm,
      respectively (P < 0.001). Fatal and nonfatal cardiovascular disease occurred in
      36 and 86 patients by 36 months, respectively. In multivariate logistic
      regression, higher calcium-phosphorus product was associated with lower serum
      fetuin A level (odds ratio, 0.96; 95% confidence interval [CI], 0.93 to 1.00; P =
      0.02). Multiple regression analysis showed that T0 serum fetuin A level was
      associated with T24 cIMT (P = 0.01) after adjustments for age, cholesterol level,
      high-sensitivity C-reactive protein level, previous cardiovascular events, and T0
      cIMT. In a multivariate Cox regression analysis, cardiovascular mortality was
      independently associated with a 1-tertile lower T0 serum fetuin A level, and a 1
      tertile higher T0 cIMT value was independently associated with greater
      cardiovascular mortality (hazard ratio, 0.45; 95% CI, 0.15 to 0.65; P = 0.007 and
      hazard ratio, 10.00; 95% CI, 3.16 to 31.73; P < 0.001, respectively) after
      adjustment for age and previous cardiovascular events. LIMITATION: Length of
      follow-up. CONCLUSION: Calcium-phosphorus product in hemodialysis patients
      inversely correlated with serum fetuin A level, which, in turn, was associated
      inversely with progression of atherosclerotic lesions and cardiovascular
      mortality in this study population.

PMID- 19167799
TI  - Page kidney as a rare cause of hypertension: case report and review of the
      literature.
AB  - Page kidney occurs by extrinsic compression of the renal parenchyma from a
      hematoma or a mass, leading to activation of the renin-angiotensin-aldosterone
      system and resulting in systemic hypertension. There have been about 100 cases of
      Page phenomenon reported in the literature. A review of cases published prior to
      1991 revealed that football and nonsports-related trauma were the most common
      causes of Page kidney. Thereafter, 28 cases have been reported in the literature,
      including our case report presented here. These recent cases show that the
      etiology of Page kidney has shifted, perhaps because of the procedure-oriented
      current practice of medicine and the increased frequency of kidney transplant
      biopsies. In addition, management options have evolved, given the more frequent
      use of medications that block the renin-angiotensin-aldosterone system and the
      availability of less invasive procedures. Page kidney should be considered in the
      differential diagnosis of secondary hypertension.

PMID- 19167800
TI  - Association between peritoneal dialysate effluent leukocytosis and amlodipine
      besylate.
AB  - Dialysate effluent leukocytosis is consistent with a greater degree of infection
      or inflammation in patients receiving peritoneal dialysis. This study describes a
      girl aged 2 years 9 months with end-stage renal disease resulting from crescent
      glomerulonephritis and severe interstitial nephritis who developed leukocytosis
      with a predominance of lymphocytes in the dialysate effluent, and in whom the
      effluent cell count normalized 1 week after discontinuation of amlodipine
      besylate therapy. Rechallenge confirmed that amlodipine was the offending agent
      causing effluent leukocytosis.

PMID- 19167801
TI  - A review of psychological correlates of adjustment in patients with multiple
      sclerosis.
AB  - Multiple Sclerosis (MS) is a chronic neurological disease which poses significant
      psychological adjustment challenges. The purpose of this systematic review was to
      identify factors that are related to adjustment in people with MS and may be
      modifiable through psychological intervention. It aimed to gain an overview of
      the strength of evidence for relationships between psychological factors and
      adjustment and identify limitations to existing studies and directions for future
      research. Seventy two studies met inclusion criteria and were included in the
      review and a narrative synthesis was conducted. A wide range of psychological
      factors have been studied in relation to adjustment outcomes. The strongest and
      most consistent finding was that perceived stress and certain emotion-focussed
      coping strategies are related to worse adjustment in MS. Uncertainty was fairly
      robustly associated with worse adjustment. There was also more tentative evidence
      available for relationships between adjustment outcomes and a range of other
      factors including social support and interactions with others, cognitive errors
      and biases, illness and symptom cognitions, control perceptions, positive
      psychology factors, and health behaviours. Implications for therapeutic
      interventions are discussed and a preliminary model of adjustment to MS is
      outlined. In light of the shortcomings of extant studies, suggestions for future
      research are offered.

PMID- 19167802
TI  - The spatial dimensions of neighborhood effects.
AB  - In the decade or so of renewed interest in neighborhood contexts and health,
      significant progress has been made conceptualizing the relationships between the
      urban environment and public health. Applied research on the link between the
      environment and health remains limited by the way spatial concepts, such as "the
      neighborhood" or "the built environment" are operationalized. In this paper we
      argue that representations of these spatial concepts in statistical models should
      be based upon the individuals, the place, and the problem under study. Through a
      series of simulation experiments we describe the sensitivity of estimates of the
      association between neighborhoods and health to the operationalization of spatial
      concepts. We explore the practice of conducting the same analysis at multiple
      scales and find that using model fit to "discover" the spatial dimension is
      problematic. In sum, there is a gap between our understanding of how the
      environment influences health and spatial statistical modeling techniques. For
      quantitative spatial inquiry into the relationship between the neighborhood
      environment and health to be effective this gap must be closed.

PMID- 19167803
TI  - Medical promise and the recalibration of expectation: hope and HIV treatment
      engagement in a transitional setting.
AB  - Globalising discourses of HIV treatment scale-up emphasise a meta-narrative of
      hope and restitution for the HIV pandemic. Between 2005 and 2007, we undertook
      qualitative baseline and longitudinal research with people living with HIV/AIDS
      in the transitional setting of Serbia. We draw here upon the thematic analyses of
      baseline and prospective interview accounts of 20 individuals. These describe a
      condition of pervasive treatment insecurity, characterised by the inconsistent
      availability of medicines for combination HIV treatment and illness monitoring
      tests. Such treatment insecurity fostered treatment doubts, and sometimes
      resistance. Narratives position treatment hope and expectation in relation to the
      collision of three forms of time horizon: 'biographical', 'clinical' and
      'transition'. Clinical time extends beyond shrinking biographical time, which is
      running out while people are constrained to wait for the treatment system to
      deliver. The uncertainty produced by this is moderated via a meta-narrative of
      transition. Transition narratives offer a bridge between old and new Europe, and
      between hope and the recalibration of expectation. They accept an inevitability
      of uncertainty while leaving open the possibility of slow progress to a better
      treatment future. This protects against a giving-up at once of self and nation
      state, and enables the continuation of the waiting game that characterises
      transition, and in which patients and expert systems engage. This study
      illustrates the double-edge of medical promise in a transitional setting. It
      shows that disjuncture between discourses of global promise and local expectation
      creates uncertainty which affected individuals have to find some way of
      accounting for.

PMID- 19167804
TI  - The Black-White difference in age trajectories of functional health over the life
      course.
AB  - This study examines whether the racial disparity in functional health grows
      unabated over the adult life course--the cumulative disadvantage hypothesis--or
      shrinks among the oldest old---the age-as-leveler hypothesis. Special emphasis is
      placed on the role of socioeconomic status (SES), which is highly associated with
      race. The analysis uses latent growth-curve modeling to examine differences in
      age trajectories of functional health between Black and White Americans and is
      based on nationally representative panel data of 3497 adults. Results cautiously
      support the age-as-leveler hypothesis. Net of functional health at baseline,
      Black adults experience a growing disadvantage in functional health over time
      until the oldest ages, when the gap in functional health begins to shrink.
      Results indicate that the potential leveling mechanisms of age may be specific to
      women. SES including financial assets explains the divergence in functional
      health across young and middle-aged Black and White adults, but not the later
      life convergence. This study reveals the life-course pattern of racial disparity
      in functional health and suggests that more theoretical development is needed in
      this field to explain why the age-as-leveler and cumulative disadvantage
      processes are different for functional health than for other outcomes.

PMID- 19167805
TI  - Neonatal outcomes after elective delivery management of preterm premature rupture
      of the membranes before 34 weeks' gestation (DOMINOS study).
AB  - OBJECTIVE: The objective was to compare the impact of the reason for delivery
      (elective delivery versus spontaneous onset of labor) on neonatal outcome after
      preterm premature rupture of the membranes (PPROMs). STUDY DESIGN: A regional
      prospective cohort study of all women with PPROM at between 24 and 34 weeks'
      gestation was conducted. We compared the effects of elective delivery (n=133),
      spontaneous labor (n=170), and admission for medical complications (n=169) like
      fetal distress, maternal hyperthermia, or placental abruption, on neonatal
      outcomes. Primary outcome measures were a composite of neonatal mortality and
      morbidity, which included periventricular leukomalacia, grade III/IV
      intraventricular hemorrhage, neonatal sepsis, and oxygen requirement at 36 weeks'
      gestation. RESULTS: Among 472 cases, mean gestational age at PPROM was 31.2+/-2.6
      weeks. Neonatal outcomes improved as gestational age advanced, but a latency
      period of over 14 days did not improve outcomes. A logistic regression analysis
      showed that only elective delivery (OR 0.41, 95%CI: 0.19-0.87, P=0.02), maternal
      age >35 years (OR 2.13, 95%CI: 1.19-3.85, P=0.01), and gestational age at rupture
      remained associated with primary outcome. CONCLUSION: Elective delivery in women
      with PPROM can be associated with decreased neonatal morbidity compared to
      spontaneous labor.

PMID- 19167806
TI  - Re: Rodolfo Montironi, Roberta Mazzuccelli, Antonio Lopez-Beltran, et al. Cystic
      nephroma and mixed epithelial and stromal tumour of the kidney: opposite ends of
      the spectrum of the same entity? Eur Urol 2008;54:1237-46.

PMID- 19167807
TI  - Editorial comment on: En bloc mobilization of the pancreas and spleen to
      facilitate resection of large tumors, primarily renal and adrenal, in the left
      upper quadrant of the abdomen: techniques derived from multivisceral
      transplantation.

PMID- 19167808
TI  - En bloc mobilization of the pancreas and spleen to facilitate resection of large
      tumors, primarily renal and adrenal, in the left upper quadrant of the abdomen:
      techniques derived from multivisceral transplantation.
AB  - BACKGROUND: The left upper quadrant of the abdomen may be occupied by a wide
      range of urologic pathology. When these lesions are large, safely resecting them
      often presents a significant technical challenge, with the possibility of
      resultant morbidity and mortality. OBJECTIVE: We describe a technique derived
      from our experience with multivisceral transplant and organ procurement, which
      provides excellent exposure of this anatomic region. DESIGN, SETTING, AND
      PARTICIPANTS: From May 1999 to April 2006, 70 patients underwent en bloc
      mobilization of the spleen and the pancreas and, as necessary, the stomach for
      masses in the left upper retroperitoneum. Pathology included malignant and benign
      lesions, including renal cell carcinoma (RCC) with or without inferior vena cava
      (IVC) involvement, adrenal tumors, retrocrural lymphadenopathy from testicular
      cancer, and transitional cell carcinoma of the renal pelvis. SURGICAL PROCEDURE:
      An extended subcostal transabdominal approach was used to resect large tumors in
      the left upper abdomen. This approach offers significant advantages over
      conventional approaches, including a flank, thoracoabdominal, or midline
      transabdominal incision with reflection of the descending colon. MEASUREMENTS:
      Intraoperative variables, including operative time, blood loss, transfusion rate,
      and extent of mobilization were recorded. Postoperative complications, including
      prolonged intubation, ileus, and deep venous thrombosis were also noted. RESULTS
      AND LIMITATIONS: Mean estimated blood loss during surgery was 973 ml. There were
      no perioperative deaths. No patients had pancreatitis or acute renal failure.
      Deep venous thrombosis was not seen. Cardiopulmonary bypass was used in one
      patient with an atrial thrombus. At a median follow-up of 42 mo, two patients
      died due to metastasis. CONCLUSIONS: Techniques acquired from organ harvesting as
      well as our experience at multivisceral transplant, such as en bloc mobilization
      of the spleen, pancreas, and stomach, can be utilized safely and effectively to
      gain excellent exposure to the left upper retroperitoneum via an extended
      subcostal incision with no additional morbidity for the patient.

PMID- 19167809
TI  - Isoliquiritigenin induces G2 and M phase arrest by inducing DNA damage and by
      inhibiting the metaphase/anaphase transition.
AB  - Isoliquiritigenin, a natural flavonoid found in licorice, shallots, and bean
      sprouts, has been demonstrated to inhibit proliferation and to induce apoptosis
      in a variety of human cancer cells. We attempted to ascertain the underlying
      mechanism by which isoliquiritigenin induced cell cycle arrest and cytotoxicity
      in HeLa human cervical cancer cells. Isoliquiritigenin treatment arrested cells
      in both G2 and M phase. The cells arrested in interphase (G2) showed markers for
      DNA damage including the formation of gamma-H2AX foci and the phosphorylation of
      ATM and Chk2, whereas the cells arrested in M phase evidenced separate poles and
      mitotic metaphase-like spindles with partially unaligned chromosomes. The
      induction of DNA damage and blockade at the metaphase/anaphase transition implied
      that isoliquiritigenin might function as a topoisomerase II poison, which was
      further demonstrated via an in vitro topoisomerase II inhibition assay. These
      results show that isoliquiritigenin inhibits topoiosmerase II activity, and the
      resultant DNA damage and arrest in mitotic metaphase-like stage contributes to
      the antiproliferative effects of isoliquiritigenin.

PMID- 19167810
TI  - Fenton-like oxidation of Rhodamine B in the presence of two types of iron (II,
      III) oxide.
AB  - The catalytic efficiency of iron (II, III) oxide to promote Fenton-like reaction
      was examined by employing Rhodamine B (RhB) as a model compound at neutral pH.
      Two types of iron (II, III) oxides were used as heterogeneous catalysts and
      characterized by XRD, Mossbauer spectroscopy, BET surface area, particle size and
      chemical analyses. The adsorption to the catalyst changed significantly with the
      pH value and the sorption isotherm was fitted using the Langmuir model for both
      solids. Both sorption and FTIR results indicated that surface complexation
      reaction may take place in the system. The variation of oxidation efficiency
      against H(2)O(2) dosage and amount of exposed surface area per unit volume was
      evaluated and correlated with the adsorption behavior in the absence of oxidant.
      The occurrence of optimum amount of H(2)O(2) or of exposed surface area for the
      effective degradation of RhB could be explained by the scavenging effect of
      hydroxyl radical by H(2)O(2) or by iron oxide surface. Sorption and
      decolourization rate of RhB as well as H(2)O(2) decomposition rate were found to
      be dependent on the surface characteristics of iron oxide. The kinetic oxidation
      experiments showed that structural Fe(II) content strongly affects the reactivity
      towards H(2)O(2) decomposition and therefore RhB decolourization. The site
      density and sorption ability of RhB on surface may also influence the oxidation
      performance in iron oxide/H(2)O(2) system. The iron (II, III) oxide catalysts
      exhibited low iron leaching, good structural stability and no loss of performance
      in second reaction cycle. The sorption on the surface of iron oxide with
      catalytic oxidation using hydrogen peroxide would be an effective oxidation
      process for the contaminants.

PMID- 19167811
TI  - Painful tonic heat stimulation induces GABA accumulation in the prefrontal cortex
      in man.
AB  - Relatively little is known on pain-induced neurotransmitter release in the human
      cerebral cortex. We used proton magnetic resonance spectroscopy (1H-MRS) during
      tonic painful heat stimulation to test the hypothesis of increases in both
      glutamate and GABA, two neurotransmitters with a key role in pain processing.
      Using a 3T MR scanner, we acquired spectra from the rostral anterior cingulate
      cortex (rACC) in 13 healthy right-handed subjects at rest and during painful heat
      stimulation. The painful stimulus consisted of a suprathreshold painful tonic
      heat pulse, which was delivered to the right upper leg via a fMRI-compatible
      Peltier element. Compared to non-painful stimulation, painful tonic heat was
      associated with a significant increase in GABA concentrations in the rACC. No
      changes in glutamate concentrations were detected during noxious stimulation.
      This study provides the first evidence that GABA is released in the human
      cerebral cortex during painful stimulation. The results are in line with animal
      findings on the role of GABA in pain processing and with studies in humans
      showing analgesic efficacy of GABA-related drugs in clinical pain conditions.

PMID- 19167812
TI  - Corticofugal outputs facilitate acute, but inhibit chronic pain in rats.
AB  - It has been widely accepted that the primary somatosensory cortex (SI) plays an
      essential role in the sensory-discriminative aspect of pain perception. However,
      it remains unclear whether the SI has a role in the descending modulation of
      pain. Although there are abundant fibers projecting back from sensory cortex to
      thalamic nuclei, and the influence of cortical modulation from SI on the thalamic
      nociceptive relay neurons has been addressed, little is known about how the
      cortical outputs modulate the nociceptive behaviors resulting from tissue injury
      or evoked by painful stimulation. The present study was designed to test whether
      the cortical outputs influenced the nociceptive behaviors using rat models of
      noxious thermal-induced acute pain, formalin-induced acute and CFA-evoked chronic
      inflammatory pain. The results showed that intracortical microinjection of GABAA
      agonist muscimol significantly reduced the first and second phase behaviors in
      formalin tests and elevated the nociceptive thresholds in the thermal stimulus
      elicited acute pain, suggesting a facilitatory influence of SI on the acute pain
      sensation. By contrast, microinjection of GABAA antagonist bicuculline remarkably
      reduced the thermal hyperalgesia of the CFA-inflamed hindpaws, indicating an
      inhibitory effect of SI output in the chronic pain state. The opposite modulatory
      effects in acute and chronic pain states suggest that there exists a functional
      switch for the SI cortex at different stages of pain disease, which is of great
      significance for the biological adaptation.

PMID- 19167814
TI  - Opposite effects of opioid blockade on the blood pressure-pain relationship in
      depressed and non-depressed participants.
AB  - The effect of the opioid antagonist naltrexone on the relationship between blood
      pressure and pain was examined in 24 participants with major depressive disorder
      and 31 non-depressed controls, before and after 25 min of stressful mental
      arithmetic. Pain was induced by immersing the non-dominant foot in 2 degrees C
      ice-water for as long as possible or until 4 min had elapsed (the cold pressor
      test). Blood pressure was measured before each cold pressor test, and at 2-min
      intervals during mental arithmetic. In the group as a whole, neither depression
      nor naltrexone influenced blood pressure at any stage of the experiment. However,
      naltrexone disrupted an association between elevated resting blood pressure and
      low levels of pain in non-depressed controls, suggesting that endogenous opioid
      peptides are involved in blood pressure-mediated analgesia. Effects were similar
      when expressed in relation to blood pressure during psychological stress. In
      contrast to controls, blood pressure was unrelated to pain in depressed
      participants in the placebo condition. However, naltrexone unmasked an
      association between blood pressure and pain--those with highest blood pressure
      reported least cold-induced pain. Thus, endogenous opioids apparently masked an
      analgesic mechanism linking elevated blood pressure with reduced sensitivity to
      pain in participants with major depressive disorder. Noradrenergic mechanisms
      involved in active coping, stress-induced analgesia and baroreflexes might
      account for these findings.

PMID- 19167815
TI  - Analgesic effects of p38 kinase inhibitor treatment on bone fracture healing.
AB  - Traditional and COX-2 selective non-steroidal anti-inflammatory drug (NSAID)
      treatment inhibits fracture healing in animal models. This indicates that either
      the inflammatory phase following a bone fracture is necessary for efficient or
      sufficient bone regeneration to heal the fracture or COX-2 may have a specific
      function during bone regeneration unrelated to inflammation. These observations
      also indicate that NSAID use during fracture healing may be contra-indicated.
      Thus, identification of different analgesics for fracture pain or other
      orthopaedic surgical procedures would be of significant clinical benefit.
      Inhibitors of p38 kinase also have significant analgesic properties. However, p38
      kinase is a critical regulator of inflammation. To assess the potential use of
      p38 kinase inhibition as a therapeutic strategy to manage fracture pain, the
      analgesic properties of SCIO-469, a p38alpha kinase inhibitor, were assessed in a
      rat fracture model and compared to other common analgesics. In addition, the
      effects of SCIO-469 treatment on ultimate fracture healing outcomes were measured
      by radiography and torsional mechanical testing. The data indicate that SCIO-469
      was an effective analgesic. No adverse events related to fracture healing were
      observed in rats treated with SCIO-469. Immunohistochemistry showed that p38
      kinase is activated primarily in the first days following a fracture. These
      observations suggest that p38alpha kinase inhibition may be an effective
      therapeutic strategy to manage orthopaedic-related pain. These observations also
      indicate that COX-2 has a specific function during bone regeneration other than
      promoting inflammation.

PMID- 19167816
TI  - Once is not enough: improved efficacy following repeated dosing with a TRPV1
      antagonist.

PMID- 19167817
TI  - In response to: "A randomized trial of behavioral physical therapy interventions
      for acute and sub-acute low back pain, by George SZ et al. [Pain 2008;140:145
      57].

PMID- 19167818
TI  - Global gene expression analysis in the mouse brainstem after hyperalgesia induced
      by facial carrageenan injection--evidence for a form of neurovascular coupling?
AB  - The present study was carried out to examine global gene expression in the
      brainstem, in a mouse facial carrageenan injection model of orofacial pain. Mice
      that received facial carrageenan injection showed increased mechanical allodynia,
      demonstrated by increased responses to von Frey hair stimulation of the face. The
      brainstem was harvested at 3 days post-injection, corresponding to the time of
      peak responses, and analyzed by Affymetrix Mouse Genome 430 2.0 microarrays. We
      sought to identify common genes that are changed in the respective sides of the
      brainstem after either right- or left-sided facial carrageenan injection. The
      result is a relatively small list of genes (22 genes), which were then classified
      using DAVID software. Many of them fell into the categories of "response to
      stress", "defence response", "response to biotic stimulus", "cell adhesion" and
      "leukocyte adhesion". Of these, increased expression of P-selectin, ICAM-1 and
      CCL12 after carrageenan injection could be verified by real-time RT-PCR on both
      the right and left sides, and increased in P-selectin and ICAM-1 further verified
      by Western blot analysis. P-selectin and ICAM-1 were immunolocalized to
      endothelial cells, and were double labelled with von Willebrand factor.
      Intraperitoneal injection of the P-selectin inhibitor KF38789 significantly
      reduced mechanical allodynia in the facial carrageenan-injected mice. P-selectin
      mediates the capturing of leukocytes from the bloodstream and rolling of
      leukocytes along the endothelial surface. We hypothesize that increased
      nociceptive input to the brainstem could attract circulating macrophages into the
      brain, resulting in neuroinflammation and pain.

PMID- 19167819
TI  - Hyperalgesia induced by spinal and peripheral hydrogen sulfide: evidence for
      involvement of Cav3.2 T-type calcium channels.
AB  - Hydrogen sulfide (H2S), a gasotransmitter, facilitates membrane currents through
      T-type Ca2+ channels, and intraplantar (i.pl.) administration of NaHS, a donor of
      H2S, causes prompt hyperalgesia in rats. In this context, we asked whether
      intrathecal (i.t.) administration of NaHS could mimic the hyperalgesic effect of
      i.pl. NaHS in rats, and then examined if Cav3.2 isoform of T-type Ca2+ channels
      contributed to the pro-nociceptive effects of i.t. and i.pl. NaHS. Either i.t. or
      i.pl. administration of NaHS rapidly decreased nociceptive threshold in rats, as
      determined by the paw pressure method. The hyperalgesia caused by i.t. and i.pl.
      NaHS was abolished by co-administration of mibefradil, a pan-T-type Ca2+ channel
      inhibitor, and also suppressed by pretreatment with i.t. and i.pl. zinc chloride,
      known to preferentially inhibit Cav3.2 among T-type Ca2+ channel isoforms,
      respectively. Repeated i.t. administration of antisense oligodeoxynucleotides
      (ODNs) targeting rat Cav3.2, but not mismatch ODNs, caused silencing of Cav3.2
      protein in the dorsal root ganglia and spinal cord, and then attenuated the
      hyperalgesia induced by either i.t. or i.pl. NaHS. Our findings thus establish
      that spinal and peripheral NaHS/H2S activates or sensitizes Cav3.2 T-type Ca2+
      channels expressed in the primary afferents and/or spinal nociceptive neurons,
      leading to sensitization of nociceptive processing and hyperalgesia.

PMID- 19167820
TI  - Acute tolerance to opioids: methodological, theoretical and clinical
      implications.

PMID- 19167821
TI  - A bibliometric analysis of the Pain journal as a representation of progress and
      trends in the field.

PMID- 19167822
TI  - Colon mustard oil instillation induced cross-organ reflex sensitization on the
      pelvic-urethra reflex activity in rats.
AB  - We investigated the participation of cyclin-dependent kinase-5 (Cdk5)-mediated N
      methyl-D-aspartate receptor (NMDAR) NR2B subunit phosphorylation in cross-organ
      reflex sensitization caused by colon irritation. The external urethral sphincter
      electromyogram (EUSE) reflex activity evoked by the pelvic afferent nerve test
      stimulation (TS, 1 stimulation/30s) and protein expression in the spinal cord and
      dorsal root ganglion tissue (T13-L2 and L6-S2 ipsilateral to the stimulation) in
      response to colon mustard oil (MO) instillation were tested in anesthetized rats.
      When compared with a baseline reflex activity with a single action potential
      evoked by the TS before the administration of test agents, MO instillation into
      the descending colon sensitized the evoked activity characterized by elongated
      firing in the reflex activity in association with increased protein levels of
      Cdk5, PSD95, and phosphorylated NR2B (pNR2B) but not of total NR2B (tNR2B) in the
      spinal cord tissue. Both cross-organ reflex sensitization and increments in
      protein expression were reversed by intra-colonic pretreatments with ruthenium
      red (a non-selective transient receptor potential vanilloid, TRPV, antagonist),
      capsaizepine (a TRPV1-selective antagonist), lidocaine (a nerve conduction
      blocker) as well as by the intra-thecal pretreatment with APV (a NRMDR
      antagonist) Co-101244 (a NR2B-selective antagonist) and roscovitine (a Cdk5
      antagonist). Moreover, compared with the control group, both the increase in
      pNR2B and the cross-organ reflex sensitization were attenuated in the si-RNA of
      NR2B rats. All these results suggested that Cdk-dependent NMDAR NR2B subunit
      phosphorylation mediates the development of cross-organ pelvic-urethra reflex
      sensitization caused by acute colon irritation which could possibly underlie the
      high concurrence of pelvic pain syndrome with irritable bowel syndrome.

PMID- 19167823
TI  - Field ionization of helium in a supersonic beam: kinetic energy of neutral atoms
      and probability of their field ionization.
AB  - High detection efficiency combined with spatial resolution on a nm-scale makes
      the field ionization process a promising candidate for spatially resolved neutral
      particles detection. The effective cross-sectional area sigma(eff) can serve as a
      measure for the effectiveness of such a field ion detector. In the present
      contribution, we combine quantum-mechanical calculations of the field-modified
      electron density distribution near the tungsten tip surface and of the resulting
      local field distributions, performed using the functional integration method,
      with a classical treatment of the atom trajectories approaching the tip in order
      to calculate the sigma(eff) values for ionization of free He atoms over an apex
      of a tungsten field emitter tip. The calculated values are compared with
      experimental data for supersonic He atomic beams at two different temperatures 95
      and 298K.

PMID- 19167824
TI  - Atom probe, AFM, and STM studies on vacuum-fired stainless steels.
AB  - The surface morphology of grades 304L and 316LN stainless steels, after low
      temperature bake-out process and vacuum annealing, has been studied by atomic
      force microscopy (AFM) and scanning tunnelling microscopy (STM). The local
      elemental composition on the surface before and after thermal treatment has been
      investigated by atom probe (AP) depth profiling measurements. After vacuum
      annealing, AFM and STM show significant changes in the surface structure and
      topology. Recrystallization and surface reconstruction is less pronounced on the
      316LN stainless steel. AP depth profiling analyses result in noticeable nickel
      enrichment on the surface of grade 304L samples. Since hydrogen recombination is
      almost controlled by surface structure and composition, a strong influence on the
      outgassing behaviour by the particular surface microstructure can be deduced.

PMID- 19167826
TI  - Seasonal differences in the efficacy of pour-on formulations of triclabendazole
      and ivermectin or abamectin against late immature liver fluke (Fasciola hepatica)
      in cattle.
AB  - Three controlled studies were conducted to determine the efficacy against late
      immature (6 weeks) Fasciola hepatica of two currently available fasciolicides
      (Genesis Ultra and Coopers Sovereign) which are applied externally to cattle.
      Efficacy of the two products was assessed when application was made under winter,
      spring and summer conditions. Efficacies for winter, spring and summer
      respectively, based on arithmetic mean total fluke counts, were 78.9%, 91.7% and
      99.6% for Coopers Sovereign and 73.4%, 89.7% and 99.6% for Genesis Ultra.
      Seasonal differences with treatment efficacy were indicated. The studies also
      confirmed previous observations that liver fluke egg counts overestimate the
      efficacy of fasciolicides and that total fluke counts is the most reliable method
      for assessing efficacy of such products.

PMID- 19167827
TI  - Changes in bacterial isolates from burn wounds and their antibiograms: a 20-year
      study (1986-2005).
AB  - BACKGROUND: Our aim is to elucidate shifts in the bacterial spectrum colonising
      burn wounds and corresponding antibiotic susceptibilities during a 20-year study
      period. METHODS: Microbiological results from burn patients collected between
      1986 and 2005 were analysed retrospectively. RESULTS: Staphylococcus aureus was
      isolated most frequently (20.8%), followed by Escherichia coli (13.9%),
      Pseudomonas aeruginosa (11.8%), coagulase-negative staphylococci (CNS) (10.9%),
      Enterococcus sp. (9.7%), Enterobacter cloacae (5.6%), Klebsiella pneumoniae (5%),
      Acinetobacter sp. (3.2%), Proteus mirabilis (2%) and Stenotrophomonas maltophilia
      (1.4%). Susceptibility of S. aureus to broad-spectrum substances such as
      ciprofloxacin or penicillinase-stable penicillins has waned, others such as
      cotrimoxazole or netilmicin remained effective. Not a single resistance against
      vancomycin was recorded. Increases in methicillin-resistant S. aureus (MRSA) were
      pronounced (3% in 1986-1997 (the first of the three study periods) to 16% in 1998
      2001 and 13% in 2002-2005). Results for methicillin-resistant CNS (MRCNS) show an
      even greater increase. P. aeruginosa has shown increasing susceptibility against
      netilmicin (1986-1989: 84%, 2002-2005: 95%). Susceptibility of P. aeruginosa to
      ceftazidime has decreased markedly. S. maltophilia has shown clinically relevant
      susceptibility mainly against ciprofloxacin. Acinetobacter sp. have shown little
      susceptibility to most antibiotics. Imipenem or meropenem have been very reliable
      reserve antibiotics throughout the study period for the fermenting
      Enterobacteriaceae (E. coli, K. pneumoniae, E. cloacae and P. mirabilis), with
      susceptibilities of or near 100%. CONCLUSION: In-depth knowledge of the bacteria
      causing infectious complications and of their antibiotic susceptibilities is a
      prerequisite for treating burn patients. Our study shows shifts in the microbial
      spectrum and their antibiogram, which mandate frequent reassessments.

PMID- 19167828
TI  - Recombinant human decorin inhibits TGF-beta1-induced contraction of collagen
      lattice by hypertrophic scar fibroblasts.
AB  - Decorin was reported to bind transforming growth factor-beta (TGF-beta(1)) and
      neutralise some of its activity as a key regulator of wound contraction and
      hypertrophic scar formation. In this study, we investigated whether recombinant
      human decorin affected TGF-beta(1)-induced fibroblast contractile activity, by
      using fibroblast-populated collagen lattice with decorin added to the collagen
      gel. Hypertrophic scar fibroblasts showed greater basal contraction of collagen
      gels than normal fibroblasts, and the addition of TGF-beta(1) significantly
      enhanced this. Decorin inhibited both the basal and TGF-beta(1)-enhanced
      contraction of collagen gel by both normal and hypertrophic scar fibroblasts.
      Decorin also inhibited TGF-beta(1)-induced alpha-smooth muscle actin (alpha-SMA),
      plasminogen activator inhibitor-1 (PAI-1) protein and mRNA expressions in normal
      and hypertrophic scar fibroblasts. These results suggest that decorin may have
      therapeutic potential for excessive skin contraction as observed in hypertrophic
      scarring.

PMID- 19167829
TI  - Factors in the choice of oral transmucosal fentanyl citrate dose for adult burns
      dressings.
AB  - Factors that influenced the choice of dose of oral transmucosal fentanyl at the
      time of burns dressing change were investigated in a prospective study. After
      Ethics committee approval, data was analysed from 29 consecutive patients who had
      been recruited and consented for a study of pain associated with burns dressings.
      Patients had completed an 11-point verbal pain intensity score (VRS) prior to and
      after the dressing change. Analgesic use during for this period was documented.
      Doses of 600 to 1200 mcg of transmucosal fentanyl (Actiq) were given based on
      individual assessment. The pre-dressing VRS (median [range]) in the 15 patients
      who received 600 mcg was 8 [3-10] and was higher than the VRS of 6 [2-9] in the
      800-1200 mcg group. The time since the burn was longer in the low dose group at 7
      [1-22] days compared with 5 [0-50] days in the higher dose group. In addition 73%
      of the low dose group was prescribed opioids regularly prior to the dressing
      compared with 57% of the high dose group. The choice of a lower transmucosal
      fentanyl dose was based on prior use of opioids and the age of the burn rather
      than on the patient's pain intensity.

PMID- 19167830
TI  - Medicolegal evaluation of aesthetic impairment: particularities of post-burn
      scars.
AB  - Burns are serious injuries with incidence decreasing with the increasing efficacy
      of prevention campaigns. Their cause may be non-intentional or criminal. Thanks
      to advances in burn management, mortality has declined; however, the sequelae are
      more severe. The medical expert must be familiar with this field in order to
      carry out precise clinical evaluation so that individual compensation may be
      determined by the judge. Aesthetic damage, which is purely a non-economic loss,
      is difficult to assess, as it is dependent on the subjective opinion of the
      medical expert. The principle of financial compensation for aesthetic impairment
      is an imperfect one, but it gives victims a satisfactory compensation to which
      they attach importance. Without detailing the various national compensation
      systems, we review the burn patient's examination by the medical expert with
      particular attention to the specific characteristics of burn scars, their course
      and aesthetic impact.

PMID- 19167831
TI  - A blunted cortisol awakening response and hippocampal atrophy in type 2 diabetes
      mellitus.
AB  - There is emerging evidence from healthy individuals, as well as direct and
      indirect evidence from psychiatric and neurological patients with disease-related
      hippocampal atrophy, linking the cortisol awakening response (CAR) to hippocampal
      volume. Type 2 diabetes mellitus (T2DM) is a metabolic disease that is also
      accompanied by hippocampal atrophy, and therefore can serve as a model for
      ascertaining the relationship between CAR and hippocampal volume. We contrasted a
      group of 18 individuals with T2DM with 12 matched controls on MRI-based
      hippocampal volume and salivary diurnal cortisol profile including CAR.
      Individuals with T2DM had smaller hippocampal volumes and exhibited a blunting of
      the CAR relative to controls, while diurnal cortisol was not affected. Across all
      subjects, fasting insulin and hippocampal volume were associated with the CAR,
      independent of diagnosis. Our findings support the hypothesis that hippocampal
      integrity is an important predictor of the CAR.

PMID- 19167832
TI  - Possible association between the androgen receptor gene and autism spectrum
      disorder.
AB  - Autism is a highly heritable disorder but the specific genes involved remain
      largely unknown. The higher prevalence of autism in men than in women, in
      conjunction with a number of other observations, has led to the suggestion that
      prenatal brain exposure to androgens may be of importance for the development of
      this condition. Prompted by this hypothesis, we investigated the potential
      influence of variation in the androgen receptor (AR) gene on the susceptibility
      for autism. To this end, 267 subjects with autism spectrum disorder and 617
      controls were genotyped for three polymorphisms in exon 1 of the AR gene: the CAG
      repeat, the GGN repeat and the rs6152 SNP. In addition, parents and affected
      siblings were genotyped for 118 and 32 of the cases, respectively. Case-control
      comparisons revealed higher prevalence of short CAG alleles as well as of the A
      allele of the rs6152 SNP in female cases than in controls, but revealed no
      significant differences with respect to the GGN repeat. Analysis of the 118
      families using transmission disequilibrium test, on the other hand, suggested an
      association with the GGN polymorphism, the rare 20-repeat allele being
      undertransmitted to male cases and the 23-repeat allele being overtransmitted to
      female cases. Sequencing of the AR gene in 46 patients revealed no mutations or
      rare variants. The results lend some support for an influence of the studied
      polymorphisms on the susceptibility for autism, but argue against the possibility
      that mutations in the AR gene are common in subjects with this condition.

PMID- 19167833
TI  - Validation of the College Alcohol Problem Scale-revised (CAPS-r) for use with non
      adjudicated first-year students.
AB  - First-year students in transition to college are at increased risk for consuming
      greater amounts of alcohol and are subject to subsequent alcohol-related
      problems. The 8-item College Alcohol Problem Scale-revised (CAPS-r) has been used
      to measure alcohol-related problems in adjudicated undergraduates and psychology
      majors. However, structural validity of the CAPS-r has not been examined in a
      general first-year student population. Confirmatory factor analysis (CFA) was
      used to test the structural validity of this two-factor model using LISREL 8.5.
      The original two-factor measurement model for the 8-item CAPS-r represented
      acceptable fit to the data (chi(2)=37.52, df=19, p=.007, CFI=.968, SRMR=.0449),
      supporting its use with first-year college students. Future studies need to
      examine invariance across ethnic, gender, and geographical groups.

PMID- 19167834
TI  - Comment on Shi et al.'s hypothesis: survivin will go much further.

PMID- 19167835
TI  - Nuclear planimetry on the samples from cytologically overlapping proliferative
      breast lesions.
AB  - Differentiation of low-grade breast carcinomas from fibroadenomas with atypia on
      fine-needle aspiration cytology material may sometimes be problematic. In some
      cytological samples of these lesions, both the nuclei of cells and patterns of
      cell clusters display substantial overlapping morphological characteristics.
      Nuclear morphometry on cytological material is suggested as an ancillary method
      for the differential diagnosis in many lesions, including breast tumors. Twenty
      five cytological samples obtained from patients with breast lesions, which were
      histopathologically confirmed as grade I ductal carcinomas (n=10), tubular
      carcinomas (n=5), and fibroadenomas with atypia (n=10), were utilized in this
      study. Eight geometric features of about 2002 nuclei from these tumors were
      measured. Discriminant analysis was performed on this data set in order to test
      the correct classification based on the eight measured variables. Statistical
      analyses were carried out with two fundamentally different approaches: in the
      first one, the entire data from all measured nuclei were used for classification.
      In the second one, a subset of data representing the 10% most deviated values of
      variables was extracted from the entire dataset to simulate the "selective
      examination" performed during classical morphologic evaluation. When the entire
      data was used in discriminant analysis, the overall performance in the correct
      classification rate was found to be approximately 50%, which was considered an
      unacceptable value in routine diagnostic practice. In the subset of data
      constructed with our systematic and reproducible "selection bias", the overall
      performance of correct classification rate of the same discriminant model
      improved substantially to 97%. Morphologic examination is actually based on
      selection. The use of data obtained from all of the cells in morphometry, as
      previously used in nearly all of the statistical methods, may cause a masking
      effect in diagnostically important features. Morphometric studies may seem to be
      useless when this effect is not taken into account. However, with a systematic
      and reproducible selection of the values with a proper "bias", morphometry may
      provide some discriminatory information in overlapping lesions.

PMID- 19167836
TI  - Clinicopathological significance of cervical adenocarcinoma associated with
      lobular endocervical glandular hyperplasia.
AB  - Lobular endocervical glandular hyperplasia (LEGH) is usually assumed to be a
      benign tumor-like lesion of the glands of the uterine cervix. However, LEGH has
      been associated with obvious cervical adenocarcinoma. The clinicopathological
      significance of coexistence of LEGH with adenocarcinoma remains unclear. We
      microscopically examined the presence or absence of LEGH components in 95 stage
      Ib cervical adenocarcinomas. Gastric mucin was detected with the use of clone
      HIK1083. Associations of the coexistence of LEGH components with
      clinicopathological variables were analyzed. LEGH components were present in 16
      cases (16.8%). Gastric mucin was positive in all 16 LEGH components, as compared
      with only 6 of the 95 adenocarcinoma components. Of the 16 adenocarcinomas with
      LEGH components, 15 were well-differentiated mucinous adenocarcinomas, and one
      was poorly differentiated adenocarcinoma. The mortality rate of tumor recurrence
      was 25% (4 of 16) in patients whose tumors had LEGH components, and 21.5% (17 of
      79) in those whose tumors had no LEGH components. There was no significant
      difference in survival. Early cervical adenocarcinoma was relatively frequently
      associated with LEGH components. LEGH may be one of the factors related to the
      development of cervical adenocarcinoma, but adenocarcinoma with LEGH components
      does not necessarily develop into a highly aggressive "adenoma malignum."

PMID- 19167837
TI  - Demodex-associated dermatologic conditions--A coincidence or an etiological
      correlate. Review with a report of a rare case of sebaceous adenoma.
AB  - Demodex folliculorum is a saprophytic mite of the human pilosebaceous unit with a
      prelidiction for facial skin and eyelashes. Infestation occurs frequently without
      symptoms; however, suppurative or granulomatous inflammation may be seen with
      high mite density. Skin lesions, such as rosacea, pityriasis, and blepharitis,
      have been attributed to Demodex; however, its role in sebaceous adenoma (SA) has
      not been reported in extensively searched medical literature. We report this rare
      case and review the skin lesions associated with Demodex folliculorum.

PMID- 19167838
TI  - Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation
      for recurrent malignant gliomas.
AB  - PURPOSE: Preclinical studies suggest that inhibition of vascular endothelial
      growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a
      monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the
      safety and efficacy of concurrent bevacizumab with brain irradiation has not been
      extensively studied. The objectives of this study were to determine the safety
      and activity of this combination in malignant gliomas. METHODS AND MATERIALS:
      After prior treatment with standard radiation therapy patients with recurrent
      glioblastoma (GBM) and anaplastic gliomas (AG) received bevacizumab (10 mg/kg
      intravenous) every 2 weeks of 28-day cycles until tumor progression. Patients
      also received 30 Gy of hypofractionated stereotactic radiotherapy (HFSRT) in five
      fractions after the first cycle of bevacizumab. RESULTS: Twenty-five patients (20
      GBM, 5 AG; median age 56 years; median Karnofsky Performance Status 90) received
      a median of seven cycles of bevacizumab. One patient did not undergo HFSRT
      because overlap with prior radiotherapy would exceed the safe dose allowed to the
      optic chiasm. Three patients discontinued treatment because of Grade 3 central
      nervous system intratumoral hemorrhage, wound dehiscence, and bowel perforation.
      Other nonhematologic and hematologic toxicities were transient. No radiation
      necrosis was seen in these previously irradiated patients. For the GBM cohort,
      overall response rate was 50%, 6-month progression-free survival was 65%; median
      overall survival was 12.5 months, and 1-year survival was 54%. DISCUSSION:
      Bevacizumab with HFSRT is safe and well tolerated. Radiographic responses,
      duration of disease control, and survival suggest that this regimen is active in
      recurrent malignant glioma.

PMID- 19167839
TI  - Radiation-induced lymphocyte apoptosis to predict radiation therapy late toxicity
      in prostate cancer patients.
AB  - PURPOSE: To examine a potential correlation between the in vitro apoptotic
      response of lymphocytes to radiation and the risk of developing late
      gastrointestinal (GI)/genitourinary (GU) toxicity from radiotherapy for prostate
      cancer. METHODS AND MATERIALS: Prostate cancer patients formerly enrolled in a
      randomized study were tested for radiosensitivity by using a radiation-induced
      lymphocyte apoptosis assay. Apoptosis was measured using flow cytometry-based
      Annexin-FITC/7AAD and DiOC(6)/7AAD assays in subpopulations of lymphocytes (total
      lymphocytes, CD4+, CD8+ and CD4-/CD8-) after exposure to an in vitro dose of 0,
      2, 4, or 8 Gy. RESULTS: Patients with late toxicity after radiotherapy showed
      lower lymphocyte apoptotic responses to 8 Gy than patients who had not developed
      late toxicity (p = 0.01). All patients with late toxicity had apoptosis levels
      that were at or below the group mean. The negative predictive value in both
      apoptosis assays ranged from 95% to 100%, with sensitivity values of 83% to 100%.
      Apoptosis at lower dose points and in lymphocyte subpopulations had a weaker
      correlation with the occurrence of late toxicity. CONCLUSIONS: Lymphocyte
      apoptosis after 8 Gy of radiation has the potential to predict which patients
      will be spared late toxicity after radiation therapy. Further research should be
      performed to identify the specific subset of lymphocytes that correlates with
      late toxicity, followed by a corresponding prospective study.

PMID- 19167840
TI  - Determining the incidence of pain flare following palliative radiotherapy for
      symptomatic bone metastases: results from three canadian cancer centers.
AB  - PURPOSE: To determine the incidence of pain flare following radiotherapy (RT) for
      painful bone metastases. MATERIALS AND METHODS: Patients with bone metastases
      treated with RT were eligible. Worst pain scores and analgesic consumption were
      collected before, daily during, and for 10 days after treatment. Pain flare was
      defined as a 2-point increase in the worst pain score (0-10) compared to baseline
      with no decrease in analgesic intake, or a 25% increase in analgesic intake with
      no decrease in worst pain score. Pain flare was distinguished from progression of
      pain by requiring the worst pain score and analgesic intake return to baseline
      levels after the increase/flare (within the 10-day follow-up period). RESULTS: A
      total of 111 patients from three cancer centers were evaluable. There were 50
      male and 61 female patients with a median age of 62 years (range, 40-89 years).
      The primary cancers were mainly breast, lung, and prostate. Most patients
      received a single 8 Gy (64%) or 20 Gy in five fractions (25%). The overall pain
      flare incidence was 44/111 (40%) during RT and within 10 days following the
      completion of RT. Patients treated with a single 8 Gy reported a pain flare
      incidence of 39% (27/70) and, with multiple fractions, 41% (17/41). CONCLUSION:
      More than one third of the enrolled patients experienced a pain flare.
      Identifying at-risk individuals and managing potential pain flares is crucial to
      achieve an optimal level of care.

PMID- 19167841
TI  - Compensating for tumor motion by a 6-degree-of-freedom treatment couch: is
      patient tolerance an issue?
AB  - PURPOSE: To determine whether patients could tolerate the motion of a robotic
      couch that compensates for breathing-induced tumor motion. METHODS AND MATERIALS:
      A total of 10 healthy subjects and 23 radio-oncology patients underwent simulated
      extracranial stereotactic radiotherapy (two 30-min sessions) on a robotic couch
      programmed to follow a fictitious tumor trajectory of 20x5x5 mm (cranio-caudal,
      left-right, and anterior-posterior directions, respectively) while rotating 2
      degrees around a cranio-caudal axis at a frequency of 5 seconds per loop.
      RESULTS: No session had to be interrupted and no nausea was induced. However, one
      patient refused the second session due to general deterioration and not all
      patients could keep their arms elevated for the entire session. CONCLUSIONS: Our
      findings showed that most patients tolerated compensatory couch motion and that
      motion sickness should not pose a problem in the investigation of this tumor
      tracking method.

PMID- 19167842
TI  - Characterization and quantification of feline fecal microbiota using cpn60
      sequence-based methods and investigation of animal-to-animal variation in
      microbial population structure.
AB  - The complex microbial community of the intestine plays a major role in animal
      health and diseases. Despite its significance to feline health and the
      significance of intestinal and fecal populations to the public health, little is
      known about the actual composition of the normal microbiota of the cat. To create
      a sequence-based inventory of feline fecal microbiota, we applied established
      methods exploiting the gene encoding the universal 60kDa chaperonin (cpn60) to
      create libraries of cloned cpn60 sequences from pooled fecal samples from five
      exclusively indoor and four outdoor, known predatory cats. Sequencing of 1248
      clones from each library revealed diverse populations dominated by Actinobacteria
      (particularly bifidobacteria) and Firmicutes (particularly lactobacilli). To
      investigate the degree of animal-to-animal variation in species abundance, ten
      targets were selected from the libraries for analysis by quantitative real-time
      PCR. Quantitative PCR results showed substantial animal-to-animal variation in
      target abundance although most targets were detected in all cats. This study lays
      the foundation for future work aimed at understanding the dynamics of intestinal
      microbial communities and their role in feline health.

PMID- 19167843
TI  - Synthesis of empty capsid-like particles of Asia I foot-and-mouth disease virus
      in insect cells and their immunogenicity in guinea pigs.
AB  - The assembly of foot-and-mouth disease virus (FMDV) requires the cleavage of the
      P12A polyprotein into individual structural proteins by protease 3C. In this
      study, we constructed a recombinant baculovirus that simultaneously expressed the
      genes for the P12A and 3C proteins of Asia I FMDV from individual promoters. The
      capsid proteins expressed in High Five insect cells were processed by viral 3C
      protease, as shown by Western blotting, and were antigenic, as revealed by their
      reactivity in an indirect sandwich-ELISA, and by immunofluorescent assay. The
      empty capsid-like particles were similar to authentic 75S empty capsids from FMDV
      in terms of their shape, size and sedimentation velocity, as demonstrated by
      sucrose gradient centrifugation. Both empty capsid-like particles and some small
      sized particles (about 10nm in diameter) were also observed using immunoelectron
      microscopy. Furthermore, the empty capsid-like particles or intermediates induced
      high levels of FMDV-specific antibodies in guinea pigs following immunization,
      and neutralizing antibodies were induced in the second week after vaccination.
      These recombinant, non-infectious, FMDV empty capsids are potentially useful for
      the development of new diagnostic techniques and vaccines.

PMID- 19167844
TI  - Antimicrobial activity of bovine psoriasin.
AB  - Human psoriasin (S100A7) has originally been described as a member of the family
      of S100 calcium-binding proteins which is overexpressed in patients suffering
      from psoriasis. The bovine homolog was first identified as a cow-derived
      respiratory allergen. As Escherichia coli mastitis is a common problem in dairy
      cattle, and human psoriasin was found to exhibit antimicrobial activity
      preferentially against E. coli, we examined whether the bovine mRNA is expressed
      in the mammary gland. To demonstrate the antimicrobial activity of bovine
      psoriasin, we isolated cDNA from the udder, cloned the bovine psoriasin gene in a
      bacterial expression vector, and the recombinant protein was expressed in BL21
      cells. The in vitro antibacterial activity was tested by performing microdilution
      susceptibility tests and radial diffusion assays with eight different bacterial
      strains, thereof three different E. coli strains, and one yeast. The
      antimicrobial activity of the recombinant bovine psoriasin is comparable with
      human psoriasin and also limited to E. coli. Psoriasin appears to be a part of
      the local host defense mechanism in the udder, is a putative candidate for a cow
      specific factor influencing mastitis susceptibility, and a possible alternative
      to conventional antibiotics.

PMID- 19167845
TI  - Delayed parturition in cloned calves associated with persistently elevated
      placentomal TGF-beta1 expression.
AB  - The objective of this study was to investigate hormonal and TGF-beta(1)
      characterizations of delayed parturition in the SCNT recipients (Korean native
      beef cattle: Hanwoo). The SCNT blastocysts produced by Hanwoo fetal fibroblast
      cells were transferred into the synchronized Hanwoo recipients. The artificially
      inseminated Hanwoo recipients (AI-R) were used as control. All AI-R were labored
      by natural delivery. The SCNT recipients (SCNT-R) with no signs of delivery were
      operated by Caesarean section. The blood and placentomes were collected during
      parturition. The weight of placentomes in SCNT-R (n=12, 301+/-41.22 g) was
      significantly higher than that of AI-R (n=10, 204.8+/-24.89 g) (p<0.05). There
      were significantly lower E2 (p<0.05) or higher P4 (p<0.01) and TGF-beta(1)
      (p<0.01) levels in the SCNT-R compared to that of AI-R, respectively. The SCNT-R
      showed a higher placentomal TGF-beta(1) protein level compared to that of AI-R
      (p<0.01). Interestingly, the TGF-beta(1) protein level in SCNT-R with normal
      delivery was dramatically decreased as same as AI-R, but it was highly maintained
      in C-sec at days 250 of pregnancy in AI-R. These results suggest that delayed
      parturition in clone calving may be associated with persistence of elevated TGF
      beta-1 expression in late pregnancy.

PMID- 19167846
TI  - Effect of suckling restriction with nose plates and premature weaning on
      postpartum anestrous interval in primiparous cows under range conditions.
AB  - Suckling and nutrition are generally recognized as two major factors controlling
      the duration of the postpartum anovulatory period. In the present study, the
      effect of premature weaning and suckling restriction with nose plates (NPs) on
      cow and calf performance was evaluated. The study was conducted over 2 years;
      primiparous Hereford cows, weighing (mean+/-S.E.M.) 344+/-3.5kg and with 4.1+/
      0.05 units of body condition score (BCS) (scale 1-8 [Vizcarra, J.A., Ibanez, W.,
      Orcasberro, R., 1986. Repetibilidad y reproductibilidad de dos escalas para
      estimar la condicion corporal de vacas Hereford. Investigaciones Agronomicas 7
      (1), 45-47]) at calving, remained with their calves until 72.5+/-1.2 days
      postpartum (day 0). They were then assigned to one of three treatments: (i)
      calves with free access to their dams and ad libitum suckling (S, n=29); (ii)
      calves fitted with NPs for 14 days, but remained with their dams (NP, n=29), and
      (iii) calves that were weaned from their dams (W, n=28). All cows were anestrus
      at the time treatments commenced (day 0). All cows were blood sampled twice
      weekly from 1 week before the beginning of the experiment until the end of the
      mating period (day 74) for progesterone analysis. The mating period began on day
      14. Cows in W treatment had ovulations earlier (P<0.05) than those in NP and S
      groups. Cows in the NP group had longer (P<0.05) intervals between the first
      progesterone increase and normal luteal phase than cows in the other two
      treatments groups (23.3+/-3.2 vs. 6.5+/-3.2 and 5.2+/-3.3 days for NP, S and W
      cows, respectively). Fifty per cent of the cows with NP had a short cycle (7
      days) but there was a group of cows that had longer (P<0.05) intervals (66 days)
      between first progesterone increase and normal estrous activity. In the NP group,
      8 of 29 cows had a short luteal phase and then a normal one; for 9 of these 29
      cows progesterone concentrations remained low for 6 weeks from the beginning of
      the treatment; and for 12 of these 29 cows progesterone concentrations initially
      increased after treatment initiation, but these animals became anestrus
      thereafter. Short-term suckling restriction with NPs led to a variable response
      in primiparous cows of moderate body condition under range conditions.

PMID- 19167847
TI  - The effects of palm kernel cake based diet on spermatogenesis in Malin x Santa
      Ines rams.
AB  - Testes from nine male Malin x Santa-Ines rams with an average body weight of
      43.1+/-3.53 kg, were used to study the effects of palm kernel cake (PKC) based
      diet on spermatogenic cells and to assess copper (Cu) levels in liver, testis and
      plasma in sheep. Animals were divided into three groups and randomly assigned
      three dietary treatments using restricted randomization of body weight in
      completely randomized design. The dietary treatments were 60% palm kernel cake
      plus 40% oil palm frond (PKC), 60% palm kernel cake plus 40% oil palm frond
      supplemented with 23 mg/kg dry matter of molybdenum as ammonium molybdate
      [(NH(4))(6)Mo(7)O(24).4H(2)O] and 600 mg/kg dry matter of sulphate as sodium
      sulphate [Na(2)SO(4)] (PKC-MS) and 60% concentrate of corn-soybean mix+40% oil
      palm frond (Control), the concentrate was mixed in a ratio of 79% corn, 20%
      soybean meal and 1% standard mineral mix. The results obtained showed that the
      number of spermatogonia, spermatocytes, spermatids and Leydig cells were not
      significantly different among the three treatment groups. However, spermatozoa,
      Sertoli cells and degenerated cells showed significant changes, which, may be
      probably due to the Cu content in PKC. Liver and testis Cu levels in the rams
      under PKC diet was found to be significantly higher (P<0.05) than rams in Control
      and PKC-MS diets. Plasma Cu levels showed a significant increase (P<0.05) at the
      end of the experiment as compared to at the beginning of the experiment for PKC
      and Control. In conclusion, spermatogenesis is normal in rams fed the diet
      without PKC and PKC supplemented with Mo and S. However spermatogenesis was
      altered in the PKC based diet probably due to the toxic effects of Cu and the
      significant changes in organs and plasma. Thus, Mo and S play a major role in
      reducing the accumulation of Cu in organs.

PMID- 19167848
TI  - Postmortem identification of hyperglycemia.
AB  - The detection of diabetic coma postmortem requires accurate biochemical analysis.
      Due to continuous consumption of glucose by surviving cells postmortem, blood
      glucose levels decrease rapidly. Therefore, vitreous fluid has been used as a
      substitute in forensic practice, since it has a very low cell count. It has been
      repeatedly reported that the sum value of vitreous glucose and lactate should be
      used to estimate the original antemortem blood glucose level, based on the
      assumption that pre-existing glucose is gradually converted to lactate under
      anaerobic conditions during agonal phase and the early postmortem period. In this
      study, we applied a strategy including consistent sampling of vitreous fluid from
      the centre of both eyes of deceased subjects as soon as possible after arrival at
      the morgue, and immediate bedside analysis using a blood gas instrument. In
      total, 3076 cases were included during 2004-2006. We found that, after an initial
      drop of vitreous glucose during the very early postmortem period, the levels
      stayed stable for appreciable time postmortem. Analysis of a second sample
      collected at autopsy 1-3 days later gave similar results (R(2)=0.90). In
      contrast, the vitreous lactate levels showed a steady increase. This implies that
      the sum value of glucose and lactate increases with postmortem time, as reflected
      by vitreous potassium level. In fact, a statistically significant difference in
      the sum value was seen between subjects with potassium below 10 mmol/L (n=1086)
      and above 20 mmol/L (n=531), p<.001. In addition, in this large material, we did
      not identify a single case with circumstantial indication of hyperglycemia that
      only showed high vitreous lactate. We therefore suggest that vitreous glucose
      alone should be used to diagnose hyperglycemia postmortem and that the limit of
      10 mmol/L should have a good specificity for diabetic coma, which theoretically
      would equal an original blood glucose value of about 26 mmol/L. As to the
      methodology, we found that sonication, centrifugation and addition of fluoride to
      the samples are unnecessary procedures when using a blood gas instrument. The
      strategy resulted in a doubling of the number of diabetic coma identified at our
      department compared to preceding period when analysis only was performed on
      selected cases.

PMID- 19167849
TI  - Primary cholesteatoma of petrous bone presenting as cervical fistula.
AB  - A unique case of primary cholesteatoma of the petrous bone is described. The
      patient presented with a cutaneous fistula of the anterior cervical triangle and
      was initially diagnosed and treated as sebaceous cyst or imflammatory lympha node
      for 3 months. Later examination showed white mass in the right external auditory
      canal and a severe conductive hearing loss. Radiological findings revealed a
      massive soft tissue consistent with cholesteatoma in the right petrous bone. The
      lesion was successfully managed with an endoscopy-assisted technique leaving the
      neurovascular structures in situ without operative complications. A review of the
      literature shows that only a few cases of cervical abscess associated with
      mastoid cholesteatoma have been reported. We also discussed the diagnosis,
      clinical features and surgical strategy for petrous bone cholesteatoma.

PMID- 19167850
TI  - A case of carbamoyl phosphate synthetase 1 deficiency presenting symptoms at one
      month of age.
AB  - Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is an autosomal recessive
      disorder of the urea cycle which causes hyperammonemia. Two forms of CPS1D are
      recognized: a lethal neonatal type and a less severe, delayed onset type.
      Neonatal CPS1D cases often present their symptoms within the first days of life.
      Delayed onset type were adolescents or adults, and infantile cases were rare. We
      report a case of CPS1D in a boy who developed symptoms at one month of age. He
      showed excellent response to treatments including continuous hemodialysis, drugs
      and a low-protein diet. His development and weight gain were good at the last
      follow-up at 1 year and three months of age. Molecular assay of the CPS1 gene
      demonstrated that the patient was heterozygous for c.2407C>G (R803G: maternal) in
      exon 20 and c.3784C>T (R1262X: paternal) in exon 32. Our clinical experience
      suggests that CPS1D could be one of the causes of hyperammonemia in early
      infantile cases.

PMID- 19167851
TI  - Plesiomonas shigelloides pneumonia.
AB  - Plesiomonas shigelloides is known to cause mild to cholera-like diarrhea in most
      infected persons. In immunocompromised patients extra-intestinal manifestations
      have been described. We report the first case of pneumonia caused by P.
      shigelloides in a 76-year-old woman who had undergone a curative gastrectomy and
      esophageal-jejunostomy due to a low differentiated adenocarcinoma of the stomach
      (pT2, pN1 pMx, G3, R0, Lauren: intestinal type). The patient was admitted in
      hospital with clinical signs of pulmonary infection. CT-scan revealed a cavernous
      lesion in the right upper pulmonary lobe. Bronchial lavage showed a granulocytic
      inflammation 105CFU/ml P. shigelloides. Although antibiotic treatment led to a
      decrease of inflammation parameters and decrease of the pulmonary infiltrate the
      patient died due to development of torsades de pointes tachycardia leading to
      ventricular fibrillation and hypoxic brain damage.

PMID- 19167852
TI  - [Yellow fever vaccination: update on rare and severe adverse effects].
AB  - Over 500million people live in yellow fever (YF) endemic areas and more than
      3million travel to endemic countries every year. Prevention against YF, caused by
      the YF virus, an arbovirus, can only be efficiently obtained by active
      immunization. The vaccine is well tolerated and severe adverse events are very
      rare. Exceptionally, YF vaccination may result in serious adverse events, such as
      viscerotropic and neurotropic diseases, sometimes with a fatal outcome. These
      rare serious adverse advents are reviewed with their potential risk factors, such
      as advanced age or history of thymus disease. The benefit/risk ratio remains in
      favour of vaccination, although the decision to offer yellow fever vaccination,
      especially to persons 60years of age or older, should be evaluated according to
      the planned trip. Additional research investigations should be made on the host
      immune response since this response is considered to be at the origin of these
      severe adverse events.

PMID- 19167853
TI  - Utility of high-resolution computed tomography for predicting risk of sputum
      smear-negative pulmonary tuberculosis.
AB  - BACKGROUND: To diagnose sputum smear-negative pulmonary tuberculosis (PTB) is
      difficult and the ability of high-resolution computed tomography (HRCT) for
      diagnosing PTB has remained unclear in the sputum smear-negative setting. We
      retrospectively investigated whether or not this imaging modality can predict
      risk for sputum smear-negative PTB. METHODS: We used HRCT to examine the findings
      of 116 patients with suspected PTB despite negative sputum smears for acid-fast
      bacilli (AFB). We investigated their clinical features and HRCT-findings to
      predict the risk for PTB by multivariate analysis and a combination of HRCT
      findings by stepwise regression analysis. We then designed provisional HRCT
      diagnostic criteria based on these results to rank the risk of PTB and blinded
      observers assessed the validity and reliability of these criteria. RESULTS: A
      positive tuberculin skin test alone among clinical laboratory findings was
      significantly associated with an increase of risk of PTB. Multivariate regression
      analysis showed that large nodules, tree-in-bud appearance, lobular consolidation
      and the main lesion being located in S1, S2, and S6 were significantly associated
      with an increased risk of PTB. Stepwise regression analysis showed that
      coexistence of the above 4 factors was most significantly associated with an
      increase in the risk for PTB. Ranking of the results using our HRCT diagnostic
      criteria by blinded observers revealed good utility and agreement for predicting
      PTB risk. CONCLUSIONS: Even in the sputum smear-negative setting, HRCT can
      predict the risk of PTB with good reproducibility and can select patients having
      a high probability of PTB.

PMID- 19167854
TI  - Analysis of heparin sodium by SAX/HPLC for contaminants and impurities.
AB  - A chromatographic method was developed for the detection and quantification of
      the contaminant oversulfated chondroitin sulfate (OSCS) and the impurity dermatan
      sulfate in heparin active pharmaceutical ingredient (API). The HPLC analysis of
      heparin is carried out using a polymer-based strong anion exchange (SAX) column
      with gradient elution from 0.125 M sodium chloride to 2.5M sodium chloride
      buffered mobile phase. The limit of detection (LOD) and limit of quantitation
      (LOQ) for the contaminant OSCS in heparin were determined to be 0.03% and 0.1%,
      respectively. The LOD and LOQ for dermatan sulfate, an impurity in heparin
      sulfate, were determined to be 0.1% and 0.8%, respectively. This manuscript is
      not a policy document and is not intended to replace either of the methods
      (capillary electrophoresis and NMR) currently required by the FDA.

PMID- 19167855
TI  - Evaluation of chemometric algorithms in quantitative X-ray powder diffraction
      (XRPD) of intact multi-component consolidated samples.
AB  - Quantitative X-ray powder diffraction (XRPD) data obtained from intact,
      consolidated samples affords the opportunity to analyze mixtures that simulate
      pharmaceutical drug products without the need for reversion back to powders; an
      analytical preparation step that destroys the contextual solid-state information
      intrinsic to intact consolidated samples. Traditional, standardless quantitative
      methods generally involve sophisticated pattern refinement procedures (e.g.,
      Rietveld refinement) and are limited to crystalline materials. Methods that
      incorporate an internal standard are not optimal for compact analysis, and may
      often be susceptible to prediction errors associated with intensity attenuation.
      Chemometric-based XRPD utilizes full-pattern methods that combine analyses of
      both Bragg diffraction and diffuse scatter, thereby allowing for enhancement of
      signal-to-noise, sensitivity, and selectivity. Classical least-squares (CLS)
      regression, principal components regression (PCR) and partial least squares (PLS)
      regression are three chemometric algorithms commonly employed in spectroscopy. In
      the present work, quantification of a consolidated four-component system,
      composed of two crystalline materials and two disordered materials was analyzed
      intact, using two different XRPD optics geometries. Calibrations constructed for
      the prediction of individual constituent concentrations using the aforementioned
      three multi-variate algorithms were statistically compared with traditional
      diffraction-absorption univariate calibration. PLS regression modeling of data
      collected in transmission geometry provided the best statistical results for the
      quantification of constituent concentration. Further, this calibration was
      minimally affected by diffraction pattern anomalies traditionally corrected prior
      to phase quantification.

PMID- 19167856
TI  - Avoiding the term 'obesity': an experimental study of the impact of doctors'
      language on patients' beliefs.
AB  - OBJECTIVE: GPs sometimes use euphemisms rather than medical terms. The present
      study aimed to explore the relative impact of using the term 'obese' compared to
      GPs' preferred euphemism on patients' beliefs about the problem. METHODS: A cross
      sectional survey followed by an experimental study was used with two conditions:
      the term 'obese' versus the GPs' preferred euphemism. In the cross sectional
      survey, GPs' (n=19) described their preferred use of term. In the experimental
      study, patients (n=449) from one General Practice in West London then completed a
      set of ratings about their beliefs following a vignette using either the term
      'obese' or the GPs' preferred euphemism. RESULTS: The first stage of the study
      showed that GPs avoided using the term 'obese' and preferred to use a euphemism.
      The most commonly used euphemism was 'your weight may be damaging your health'.
      The second stage showed that the term 'obese' made patients believe that the
      problem had more serious consequences and made them feel more anxious and upset
      than when the same symptoms were labelled using the euphemism. When analysed
      according to the patient's own BMI, however, the results showed that the term
      'obese' had a greater emotional impact than the euphemism only on patients who
      were not obese; obese patients found the euphemism more upsetting. CONCLUSION:
      GPs avoid using the term 'obese' for fear of upsetting patients. This term,
      whilst making the problem appear more serious is only more upsetting for non
      obese patients. PRACTICE IMPLICATIONS: GPs choice of term therefore needs to
      reflect whether they want the patients to be upset or whether they want them to
      accept the seriousness of their problem.

PMID- 19167858
TI  - REG1A predicts recurrence in stage Ta/T1 bladder cancer.
AB  - AIMS: Stage Ta/T1 urothelial carcinoma of the bladder (Ta/T1 BC) has a marked
      tendency to recur. Regenerating protein 1 A (REG1A) has been reported to be
      expressed in human cancers, and it may be positively correlated with patient's
      prognosis. The aim of the present study was to evaluate the prognostic value of
      REG1A in Ta/T1 BC. METHODS: Immunohistochemistry was done on 110 paraffin
      embedded specimens of human Ta/T1 BC to detect the proteins REG1A, PCNA and MMP2.
      The relationships between REG1A expression and the clinical-pathological
      characteristics of Ta/T1 BC patients were evaluated. RESULTS: Sixty-five out of
      110 specimens were REG1A-positive. Grade and expression levels of MMP2 and REG1A
      were significantly correlated with the recurrence rate. REG1A expression (Hazard
      ratio: 3.1; 95% CI: 1.1-8.5; P=0.030) was an independent predictor of recurrence
      rate in multivariate Cox regression analysis. A significant association between
      REG1A expression and MMP2 expression (P=0.023) was also observed. CONCLUSION:
      Expression of REG1A is an independent predictor of recurrence in Ta/T1 BC.

PMID- 19167857
TI  - Literacy-appropriate educational materials and brief counseling improve diabetes
      self-management.
AB  - OBJECTIVE: In this pilot study, we evaluated the impact of providing patients
      with a literacy-appropriate diabetes education guide accompanied by brief
      counseling designed for use in primary care. METHODS: We provided the Living with
      Diabetes guide and brief behavior change counseling to 250 English and Spanish
      speaking patients with type 2 diabetes. Counseling sessions using collaborative
      goal setting occurred at baseline and by telephone at 2 and 4 weeks. We measured
      patients' activation, self-efficacy, diabetes distress, knowledge, and self-care
      at baseline and 3-month follow-up. RESULTS: Statistically significant
      (p<or=0.001) and clinically important (effect sizes=0.29-0.42) improvements were
      observed in participants' activation, self-efficacy, diabetes-related distress,
      self-reported behaviors, and knowledge. Improvements were similar across literacy
      levels. Spanish speakers experienced both greater improvement in diabetes-related
      distress and less improvement in self-efficacy levels than English speakers.
      CONCLUSION: A diabetes self-management support package combining literacy
      appropriate patient education materials with brief counseling suitable for use in
      primary care resulted in important short-term health-related psychological and
      behavioral changes across literacy levels. PRACTICE IMPLICATIONS: Coupling
      literacy-appropriate education materials with brief counseling in primary care
      settings may be an effective and efficient strategy for imparting skills
      necessary for diabetes self-management.

PMID- 19167859
TI  - Assessment of survival advantage in ampullary carcinoma in relation to tumour
      biology and morphology.
AB  - INTRODUCTION: Carcinoma of the ampulla of Vater is said to carry a significantly
      better prognosis than pancreatic ductal adenocarcinomas arising in the pancreatic
      head. However, it is uncertain as to whether this is due to the fact that they
      have differing oncological characteristics or simply an earlier presentation as a
      result of the exophytic morphology of ampullary lesions causing obstruction of
      the bile ducts. METHODS: All patients undergoing pancreaticoduodenectomy between
      January 1998 and December 2004 were identified from a prospectively maintained
      database. Patients with a pathologically confirmed ampullary (AMP) tumour were
      compared to those with a carcinoma of the head of the pancreas (HOP). Tumour
      characteristics including size, stage and degree of differentiation were analysed
      as were survival data. RESULTS: 71 AMP and 144 HOP tumours were resected during
      the period studied and had full histology reports available for assessment. The
      median diameter of the AMP tumours was significantly less than those of the HOP
      (2 cm vs. 3 cm; p = 0.04). The T stage distribution differed significantly
      between the AMP and HOP tumours in favour of the former (Stages I--10 vs. 0 (p =
      0.03); II--29 vs. 13 (p = 0.04); III--25 vs. 121 (p = 0.01); IV--7 vs. 10). The
      number of resection specimens with positive lymph nodes was lower in the AMP
      group (31 vs. 121; p = 0.03) as was the prevalence of vascular invasion (33 vs.
      114; p = 0.006) and neural invasion (23 vs. 134; p = 0.009). There was no
      difference in the degree of differentiation of the AMP and HOP tumours. The 5
      year survival rates were significantly better in the AMP group at 60% vs. 20% (p
      = 0.008). Subdivision of AMP carcinoma into polypoid (60%) and ulcerating (40%)
      lesions revealed a non-significant survival advantage in favour of polypoid
      tumours at (64% vs. 60%; p = 0.07) at 5 years. CONCLUSIONS: The outcome of
      resection for AMP is significantly better than for pancreatic ductal
      adenocarcinomas arising in the periampullary region. Although the anatomical
      position of AMP tumours may contribute to this survival advantage, the HOP
      tumours exhibit more adverse histological features suggesting that they are
      different diseases and hence the difference in survival.

PMID- 19167860
TI  - Relationship between period of survival and clinicopathological characteristics
      in patients with colorectal liver metastasis.
AB  - AIM: Cancer death in the early period after hepatectomy still occurs in patients
      with colorectal liver metastasis (CLM). We examined the relationship between
      clinicopathological parameters and survival periods in 130 CLM patients who
      underwent hepatectomy. PATIENTS/METHODS: Patients were divided into four groups:
      Group 1 (5-year survivors without tumor relapse), Group 2 (survivors at 2-5
      years), Group 3 (cancer death at 2-5 years), and Group 4 (cancer death within 2
      years). RESULTS: A short surgical margin was frequent in Group 4 compared to
      Group 1 (31 vs. 78%, P<0.05). Primary node-positive status, absence of fibrous
      pseudo-capsular formation, higher Clinical Risk Score, and tumor recurrence
      within 12 months were frequent in Group 4 (P<0.05). Multivariate analysis
      revealed a short surgical margin (HR; 3.5) and early tumor relapse (HR; 5.9) as
      independently significant related parameters (P<0.05). CONCLUSIONS: Sufficient
      surgical margins and careful follow-up for early tumor relapse may be important
      for improving postoperative outcomes for CLM patients.

PMID- 19167861
TI  - [Study on personality and psychiatric disorder in fibromyalgia].
AB  - WORK INTEREST: To assess vulnerability factors of outpatients with fibromyalgia,
      by the evaluating prevalence of DSM-IV axis I disorders (mental disorders) and
      axis II disorders (personality disorders). METHODS: 30 outpatients with
      fibromyalgia were examined consecutively, and were administered the Mini
      International Neuropsychiatric Interview and the Structured Clinical Interview
      for DSM-IV. RESULTS: The patients were found to have a high prevalence of DSM-IV
      axis I disorders (63,3% received a diagnosis of depressive and/or anxious
      disorder), and axis II disorders (46,7% received at least one diagnosis of
      personality disorder, including obsessive-compulsive personality disorder: 30%,
      borderline personality disorder: 16,7%, and depressive personality disorder:
      16,7%). PERSPECTIVES: Our results show the importance of psychiatric
      comorbidities, including personality disorders from outpatients with
      fibromyalgia. Personality disorders have to be taken into account in the
      treatment by their impact on doctor-patient relation. Our results suggest the
      importance of liaison psychiatry in the treatment of those patients.

PMID- 19167862
TI  - Pancreatic tuberculosis: a rare cause of pseudoneoplasic obstructive jaundice.

PMID- 19167863
TI  - [Occlusive complications related to Meckel diverticulum].

PMID- 19167864
TI  - [Atypical sore throats].

PMID- 19167865
TI  - A novel kernel-based maximum a posteriori classification method.
AB  - Kernel methods have been widely used in pattern recognition. Many kernel
      classifiers such as Support Vector Machines (SVM) assume that data can be
      separated by a hyperplane in the kernel-induced feature space. These methods do
      not consider the data distribution and are difficult to output the probabilities
      or confidences for classification. This paper proposes a novel Kernel-based
      Maximum A Posteriori (KMAP) classification method, which makes a Gaussian
      distribution assumption instead of a linear separable assumption in the feature
      space. Robust methods are further proposed to estimate the probability densities,
      and the kernel trick is utilized to calculate our model. The model is
      theoretically and empirically important in the sense that: (1) it presents a more
      generalized classification model than other kernel-based algorithms, e.g., Kernel
      Fisher Discriminant Analysis (KFDA); (2) it can output probability or confidence
      for classification, therefore providing potential for reasoning under
      uncertainty; and (3) multi-way classification is as straightforward as binary
      classification in this model, because only probability calculation is involved
      and no one-against-one or one-against-others voting is needed. Moreover, we
      conduct an extensive experimental comparison with state-of-the-art classification
      methods, such as SVM and KFDA, on both eight UCI benchmark data sets and three
      face data sets. The results demonstrate that KMAP achieves very promising
      performance against other models.

PMID- 19167866
TI  - Lack of potassium current in W309R mutant KCNQ3 channel causing benign familial
      neonatal convulsions (BFNC).
AB  - BFNC is an autosomal dominant epileptic disorder caused by mutations of KCNQ2 or
      KCNQ3 potassium channel gene. W309R missense mutation in KCNQ3 gene was
      previously reported in a family with BFNC. In this study, potassium currents were
      recorded from HEK293 cells expressing both W309R mutant KCNQ3 and wild type KCNQ2
      channels. We found a lack of potassium current in W309R mutant KCNQ3 and KCNQ2
      channels, which can explain the hyper-excitability of CNS in patients with BFNC.

PMID- 19167867
TI  - Polymorphisms of MTHFR gene associated with livedoid vasculopathy in Taiwanese
      population.

PMID- 19167868
TI  - Kollidon SR colloidal particles as vehicles for oral morphine delivery in pain
      treatment.
AB  - Due to the great importance of new therapeutic routes for morphine in pain
      treatment, several investigations are under development. In this way, the design
      of a liquid system for the oral administration of morphine would be of great
      help, especially in patients with difficulties in swallowing (children and
      elderly people). The systems studied in this work are kollidon SR microparticles,
      a biodegradable polymer classically used as excipient in the design of solid
      dosage forms, as vehicles for morphine. A detailed investigation of the
      capabilities of the polymer particles to load this drug at their surface is
      described. Electrophoretic mobility and optical absorbance determinations were
      used with this aim. The main factors determining the drug incorporation, after
      incubation of the microparticles in the morphine solutions, were the adsorption
      time, the type of electrolyte and its concentration, and the drug concentration.
      The optimum loading conditions were used to perform morphine release evaluations,
      finding that the release profiles were biphasic since the drug adsorbed was
      slowly released during 24h after an initial burst release phase.

PMID- 19167870
TI  - [Effect of hydroxyurea on adhesion proteins in sickle cell anemia].

PMID- 19167869
TI  - Gel formation in systems composed of drug containing catanionic vesicles and
      oppositely charged hydrophobically modified polymer.
AB  - The aim of this study was to explore if mixtures of drug containing catanionic
      vesicles and polymers give rise to gel formation, and if so, if drug release from
      these gels could be prolonged. Catanionic vesicles formed from the drug
      substances alprenolol or tetracaine, and the oppositely charged surfactant sodium
      dodecyl sulphate were mixed with polymers. Three polymers with different
      properties were employed: one bearing hydrophobic modifications, one positively
      charged and one positively charged polymer bearing hydrophobic modifications. The
      structure of the vesicles before and after addition of polymer was investigated
      by using cryo-TEM. Gel formation was confirmed by using rheological measurements.
      Drug release was studied using a modified USP paddle method. Gels were observed
      to form only in the case when catanionic vesicles, most likely with a net
      negative charge, were mixed with positively charged polymer bearing lipophilic
      modifications. The release of drug substance from these systems, where the
      vesicles are not trapped within the gel but constitute a founding part of it,
      could be significantly prolonged. The drug release rate was found to depend on
      vesicle concentration to a higher extent than on polymer concentration.

PMID- 19167871
TI  - Global assessment of the COPD patient: time to look beyond FEV1?
AB  - COPD is a diverse disease entity with multiple dimensions that uniquely define
      the patient's performance, morbidity and mortality. FEV(1) is both the
      traditional metric used to define the progression of COPD as well as the
      strongest spirometric predictor of mortality in COPD patients. However, besides
      pulmonary functional abnormalities, COPD is also associated with significant
      systemic effects. Therefore, the global assessment of an affected patient should
      include different aspects of the consequences of this disorder, beyond the "gold
      standard" assessment of airflow limitation. Quantification of the patient's
      dyspnea, body composition as expressed by BMI, simple measures of exercise
      capacity such as the 6MWD, assessment of comorbidities and identification of
      characteristics related to different phenotypes are features that may lead to
      more optimal management of such patients.

PMID- 19167872
TI  - Calling heads from tails: the role of mathematical modeling in understanding cell
      polarization.
AB  - Theorists have long speculated on the mechanisms driving directed and spontaneous
      cell polarization. Recently, experimentalists have uncovered many of the
      mechanisms underlying polarization, enabling these models to be directly tested.
      In the process, they have demonstrated the explanatory and predictive value of
      these models and, at the same time, uncovered additional complexities not
      currently explained by them. In this review, we discuss some of main theories
      regarding cell polarization and highlight how the intersection of mathematical
      and experimental biology has yielded new insights into these mechanisms in the
      case of budding yeast and eukaryotic chemotaxis.

PMID- 19167873
TI  - Safety problems among heavy-drinking youth at a Bulgarian nightlife resort.
AB  - BACKGROUND: Vacations at international nightlife resorts represent an important
      but also risky element in the lives of youth in many countries. There is an
      urgent need for evaluating the role played by bars and nightclubs in producing
      and reducing risks; this task is important, especially at upcoming nightlife
      resorts with limited experience in managing young partygoers from other
      countries. METHODS: Seven weeks of ethnographic fieldwork was conducted during
      the summer 2007 at the emerging Bulgarian nightlife resort, Sunny Beach. The
      research instrument "KAReN" was used as a guideline to evaluate the safety
      conditions in nine bars and three nightclubs. RESULTS: The evaluation highlights
      five key factors at the venues that put young tourists in danger: violent
      security staff, overcrowding, shattered glass on the floor, dancing on furniture,
      and irresponsible alcohol serving. Action is needed to improve the safety
      conditions at the venues of Sunny Beach and other nightlife resorts. The
      improvements call for integrated strategies involving travel agencies, local
      authorities, health services, tourists and venues.

PMID- 19167874
TI  - The effects of daily cover soils on shear strength of municipal solid waste in
      bioreactor landfills.
AB  - Bioreactor landfills are operated to enhance refuse decomposition, gas
      production, and waste stabilization. The major aspect of bioreactor landfill
      operation is the recirculation of collected leachate back through the refuse
      mass. Due to the accelerated decomposition and settlement of solid waste,
      bioreactor landfills are gaining popularity as an alternative to the conventional
      landfill. The addition or recirculation of leachate to accelerate the waste
      decomposition changes the geotechnical characteristics of waste mass. The daily
      cover soils, usually up to 20-30% of total MSW volumes in the landfill, may also
      influence the decomposition and shear strength behavior of MSW. The objective of
      this paper is to study the effects of daily covers soils on the shear strength
      properties of municipal solid waste (MSW) in bioreactor landfills with time and
      decomposition. Two sets of laboratory-scale bioreactor landfills were simulated
      in a laboratory, and samples were prepared to represent different phases of
      decomposition. The state of decomposition was quantified by methane yield, pH,
      and volatile organic content (VOC). Due to decomposition, the matrix structure of
      the degradable solid waste component was broken down and contributed to a
      significant decrease in the reinforcing effect of MSW. However, the daily cover
      soil, a non-degradable constituent of MSW, remains constant. Therefore, the
      interaction between daily cover soil particles and MSW particles will affect
      shear strength behavior. A number of triaxial tests were performed to evaluate
      the shear strength of MSW. The test results indicated that the shear strength of
      MSW was affected by the presence of cover soils. The friction angle of MSW with
      the presence of cover soil is higher than the friction angle of MSW without any
      cover soils. The friction angle of MSW increased from 27 degrees to 30 degrees
      due to the presence of cover soils for Phase 1 samples. The increased strength
      was attributed to the friction nature of sandy soil that was used as daily covers
      soils. Therefore, the effects of cover soils on the shear strength properties of
      MSW should be evaluated and taken into consideration during stability analyses
      and design.

PMID- 19167875
TI  - An assessment of bioreactor landfill costs and benefits.
AB  - Because effective operation of bioreactor landfills involves careful operation
      and construction of infrastructure beyond that necessary in traditional
      landfills, upfront capital and operating costs are greater than those associated
      with traditional landfills. Prior to investing in bioreactor landfills, landfill
      owners must be convinced that larger short-term expenses (e.g., liquid and/or air
      injection infrastructure) will be balanced by future economic benefits (e.g.,
      extension of landfill life, reduced leachate treatment costs, etc.). The purpose
      of this paper is to describe an economic model developed to evaluate the impact
      of various operational (anaerobic, aerobic, or hybrid) and construction (retrofit
      and as-built) bioreactor landfill strategies on project economics. Model results
      indicate retrofit bioreactor landfills are more expensive than traditional
      landfills, while both the as-built and aerobic bioreactor landfills are less
      costly. Simulation results indicate the parameters that influence bioreactor
      economics most significantly are airspace recovery, gas recovery and subsequent
      use to generate electricity, and savings resulting from reduced leachate
      treatment costs.

PMID- 19167876
TI  - Microbial characterization during composting of biowaste.
AB  - Windrow composting of source-separated biowaste was studied in a pilot plant in
      Crete, with regard to abiotic factors, gas concentration in the pile and
      succession of functional microbial groups. The pH, C/N ratio and VS content, as
      well as the O(2) and CO(2) concentration, correlated well with composting time,
      indicating typical composting behaviour. Most of the microbial groups examined
      exhibited their highest counts towards the end of the thermophilic phase, with
      declining trends thereafter. The population of total mesophilic and thermophilic
      bacteria increased during the mild thermophilic phase and followed the
      temperature decline thereafter. Results on these microbial groups and fungi
      indicate that the timing of the thermophilic stage in the composting process, in
      addition to the peak temperature and duration of the stage, affects the microbial
      succession. Escherichia coli were detected for over 2 months of processing, in
      spite of the high temperatures achieved; only after about 3 months of composting
      did its population decline below the detection limit.

PMID- 19167877
TI  - Inconsistent pathways of household waste.
AB  - The aim of this study was to provide policy-makers and waste management planners
      with information about how recycling programs affect the quantities of specific
      materials recycled and disposed of. Two questions were addressed: which factors
      influence household waste generation and pathways? and how reliable are official
      waste data? Household waste flows were studied in 35 Swedish municipalities, and
      a wide variation in the amount of waste per capita was observed. When evaluating
      the effect of different waste collection policies, it was found to be important
      to identify site-specific factors influencing waste generation. Eleven municipal
      variables were investigated in an attempt to explain the variation. The amount of
      household waste per resident was higher in populous municipalities and when net
      commuting was positive. Property-close collection of dry recyclables led to
      increased delivery of sorted metal, plastic and paper packaging. No difference
      was seen in the amount of separated recyclables per capita when weight-based
      billing for the collection of residual waste was applied, but the amount of
      residual waste was lower. Sixteen sources of error in official waste statistics
      were identified and the results of the study emphasize the importance of reliable
      waste generation and composition data to underpin waste management policies.

PMID- 19167878
TI  - PCR-coupled electrochemical sensing of Legionella pneumophila.
AB  - Human infections with Legionella pneumophila represent a public health problem.
      Current culture assays for surveillance and control of L. pneumophila in water
      are time-consuming and limited by the sensitivity, especially when samples also
      contain microorganisms that inhibit Legionella growth. In this work, an
      electrochemical method, different from real-time polymerase chain reaction (PCR)
      approaches, for semiquantitative evaluation of L. pneumophila is presented. A PCR
      assay targeting the 16S-rRNA gene of L. pneumophila giving rise to a 95-mer
      amplicon was established. Amplicons were hybridized to a biotin-labeled reporter
      sequence and then to a thiolated stem-loop structure immobilized onto gold
      electrodes as a reporter molecule with 1-naphthyl phosphate as a substrate. 1
      Naphthol enzymatically generated was determined by differential pulse voltammetry
      (DPV). For a constant number of amplification cycles, results show that the
      voltammetric signal is related to the number of copies in the sample thus
      achieving a useful semiquantitative estimation of L. pneumophila. After 40 cycles
      of PCR amplification this methodology has a limit of detection of 10 genomes,
      allowing the reliable detection of 10(2) genomes of L. pneumophila as well as
      distinguishing 10(3) and 10(4) genomes of the pathogen, values related to
      corrective actions in water systems in buildings, in accordance with the
      legislation currently in force.

PMID- 19167879
TI  - Electrochemical impedance spectroscopy to study physiological changes affecting
      the red blood cell after invasion by malaria parasites.
AB  - The malaria parasite, Plasmodium falciparum, invades human erythrocytes and
      induces dramatic changes in the host cell. The idea of this work was to use RBC
      modified electrode to perform electrochemical impedance spectroscopy (EIS) with
      the aim of monitoring physiological changes affecting the erythrocyte after
      invasion by the malaria parasite. Impedance cell-based devices are potentially
      useful to give insight into cellular behavior and to detect morphological
      changes. The modelling of impedance plots (Nyquist diagram) in equivalent circuit
      taking into account the presence of the cellular layer, allowed us pointing out
      specific events associated with the development of the parasite such as (i)
      strong changes in the host cell cytoplasm illustrated by changes in the film
      capacity, (ii) perturbation of the ionic composition of the host cell illustrated
      by changes in the film resistance, (iii) releasing of reducer (lactic acid or
      heme) and an enhanced oxygen consumption characterized by changes in the charge
      transfer resistance and in the Warburg coefficient characteristic of the redox
      species diffusion. These results show that the RBC-based device may help to
      analyze strategic events in the malaria parasite development constituting a new
      tool in antimalarial research.

PMID- 19167880
TI  - Development of a stable cholesterol biosensor based on multi-walled carbon
      nanotubes-gold nanoparticles composite covered with a layer of chitosan-room
      temperature ionic liquid network.
AB  - A novel amperometric biosensor was fabricated based on the immobilization of
      cholesterol oxidase (ChOx) into a cross-linked matrix of chitosan (Chi)-room
      temperature ionic liquid (IL) (1-butyl-3-methylimidazolium tetrafluoroborate).
      Initially, the surface of bare electrode (indium tin oxide coated glass) was
      modified with the electrodeposition of Au particles onto thiol (-SH)
      functionalized multi-walled carbon nanotubes (MWNTs). The biosensor electrode is
      designated as MWNT(SH)-Au/Chi-IL/ChOx. Scanning electron microscopy image of
      MWNT(SH)-Au/Chi-IL/ChOx reveals that Chi-IL exists as the interconnected wires
      covering the Au particles on the surface of MWNT(SH)-Au. Cyclic voltammetry and
      chronoamperometry were used for the electrochemical determination of cholesterol
      at the biosensor electrode, MWNT(SH)-Au/Chi-IL/ChOx. The presence of Au particles
      in the matrix of CNTs provides an environment for the enhanced electrocatalytic
      activities. The MWNT(SH)-Au/Chi-IL/ChOx biosensor exhibited a linear response to
      cholesterol in the concentration range of 0.5-5mM with a correlation coefficient
      of 0.998, good sensitivity (200 microAM(-1)), a low response time ( approximately
      7s), repeatability (R.S.D value of 1.9%) and long term stability (20 days with a
      decrease of 5% response). The synergistic influence of MWNT(SH), Au particles,
      Chi and IL contributes to the excellent performance for the biosensor.

PMID- 19167881
TI  - Molecular prediction of early recurrence after resection of hepatocellular
      carcinoma.
AB  - The prognosis of hepatocellular carcinoma (HCC) remains poor. Vascular invasion,
      tumour multiplicity and large tumour size are the conventional poor prognostic
      indicators related to early recurrence. However, it is difficult to predict
      prognosis of each HCC in the absence of these indicators. The purpose of this
      study is to predict early recurrence of HCC after radical resection based on
      whole human gene expression profiling. Microarray analyses were performed in 139
      HCC primary tumours. A total of 88 cases lacking the conventional poor prognostic
      indicators were analysed to establish a molecular prediction system
      characteristic for early recurrence in 42 training cases with two polarised
      prognoses, and to test its predictive performance in 46 independent cases (group
      C). Subsequently, this system was applied to another 51 independent cases with
      some poor prognostic indicators (group D). The molecular prediction system
      accurately differentiated HCC cases into poor and good prognoses in both the
      independent group C (disease-free survival [DFS]: p=0.029, overall survival [OS]:
      p=0.0043) and independent group D (DFS: p=0.0011, OS, p=0.035). Multivariate Cox
      regression analysis indicated that the clinical value of molecular prediction
      system was an independent prognostic factor (p<0.0001, hazard ratio=3.29). Gene
      expression pattern related to early intrahepatic recurrence inherited in the
      primary HCC tumour can be useful for the prediction of prognosis.

PMID- 19167882
TI  - Deconstructing estradiol: removal of B-ring generates compounds which are potent
      and subtype-selective estrogen receptor agonists.
AB  - Estradiol and related estrogens have been widely used as supplements to relieve
      menopausal symptoms, but they lead to an increased risk of breast and endometrial
      cancer. Here we report the synthesis of a new family of compounds where we have
      removed the B-ring from the steroid ABCD structure, and functionalized the A
      ring. These A-CD compounds show a preferential affinity for the estrogen receptor
      subtype ERbeta. Some show binding affinities which are greater than estradiol.
      The presence of electron-withdrawing substituents on the A-ring should reduce the
      tendency of these compounds to form carcinogenic metabolites, so they might lead
      to a safer approach to hormone replacement therapy.

PMID- 19167883
TI  - Tricyclic HIV integrase inhibitors: VI. SAR studies of 'benzyl flipped' C3
      substituted pyrroloquinolines.
AB  - A series of C3 halobenzyl-substituted tricyclic HIV integrase inhibitors was
      prepared. Improvement in cell-based inhibitor potency was observed in comparison
      to previously disclosed tricyclic pyrroloquinolines carrying the 'halobenzyl
      tail' at the lactam nitrogen. Animal PK for several of the C3-substituted
      inhibitors was examined, with a dihaloaryl analog achieving good balance in
      protein-shifted EC(50) and t(1/2) in animal PK studies.

PMID- 19167884
TI  - The design and discovery of novel amide CCR5 antagonists.
AB  - The synthesis of a range of novel amine-containing structures and their primary
      potency as inhibitors of HIV-1 fusion via blocking of the CCR5 receptor is
      described. The development of the medicinal chemistry strategy and SAR's which
      led to the identification of the piperidine amide compounds 33 and 36 as
      excellent leads for further evaluation is described, along with key
      physicochemical data which highlighted their lead potential.

PMID- 19167885
TI  - Synthesis and SAR of potent LXR agonists containing an indole pharmacophore.
AB  - A novel series of 1H-indol-1-yl tertiary amine LXR agonists has been designed.
      Compounds from this series were potent agonists with good rat pharmacokinetic
      parameters. In addition, the crystal structure of an LXR agonist bound to
      LXRalpha will be disclosed.

PMID- 19167886
TI  - 5-Hydroxyindole-type alkaloids, as Candida albicans isocitrate lyase inhibitors,
      from the tropical sponge Hyrtios sp.
AB  - Chemical investigations of the tropical marine sponge Hyrtios sp. have resulted
      in the isolation of a new alkaloid, 1-carboxy-6-hydroxy-3,4-dihydro-beta
      carboline (1) together with the known metabolites, 6-hydroxy-3,4-dihydro-1-oxo
      beta-carboline (2), 5-hydroxy-1H-indole-3-carboxylic acid methyl ester (3),
      serotonin (4), hyrtiosin A (5), 5-hydroxyindole-3-carbaldehyde (6), and hyrtiosin
      B (7). Their structures were elucidated on the basis of mass spectrometry and
      detailed 2D NMR spectroscopic data. Hyrtiosin B (7) displayed a potent inhibitory
      activity against isocitrate lyase (ICL) of Candida albicans with an IC(50) value
      of 89.0 microM.

PMID- 19167887
TI  - Elucidation of the mechanism producing menaquinone-4 in osteoblastic cells.
AB  - Vitamin K is an essential nutrient and a cofactor for the carboxylation of
      specific glutamyl residues of proteins to gamma-glutamyl residues, which
      activates osteocalcin related to bone formation. Among vitamin K homologues,
      menaquinone-4 (MK-4) is the most active biologically, up-regulating the gene
      expression of bone markers, and thus has been clinically used in the treatment of
      osteoporosis in Japan. Recently, we confirmed that MK-4 was converted from
      dietary phylloquinone (PK), and then accumulated in various tissues at high
      concentrations. This system should play an important role in biological functions
      including bone formation, however, the pathway by which MK-4 is converted remains
      unclear. In this study, we studied the mechanism of MK-4's conversion with
      chemical techniques using deuterated analogues.

PMID- 19167888
TI  - Novel 1,4-diarylpiperidine-4-methylureas as anti-hyperlipidemic agents: dual
      effectors on acyl-CoA:cholesterol O-acyltransferase and low-density lipoprotein
      receptor expression.
AB  - A family of 1,4-diarylpiperidine-4-methylureas were designed and synthesized as
      novel dual effectors on ACAT and LDL receptor expression. We examined SAR of the
      synthesized compounds focusing on substitution at the three aromatic parts of the
      starting compound 1 and succeeded in identifying essential substituents for
      inhibition of ACAT and up-regulation of hepatic LDL receptor expression.
      Especially, we found that compound 12f, which can easily be prepared, has
      biological properties comparable to those of SMP-797, a promising ACAT inhibitor.
      In addition, the in vitro effects of 12f on lipid metabolism were substantially
      superior to those of a known ACAT inhibitor, Avasimibe.

PMID- 19167889
TI  - Activity limitations in patients with neuromuscular disorders: a responsiveness
      study of the ACTIVLIM questionnaire.
AB  - Recently, a self-reported scale of activity limitations, the ACTIVLIM
      questionnaire, was developed and validated in patients with neuromuscular
      disorders (NMD). The purpose of this study was to investigate its sensitivity to
      change. One hundred thirty-two patients with NMD (mean age, range: 31, 6-80) were
      assessed twice, with 21+/-4 months in between, using the ACTIVLIM questionnaire.
      Mean score change, effect size, standardized response, mean paired t-test and an
      individual-level statistical approach were calculated for groups of patients
      according to their self-rated functional status evolution and for three main
      diagnostic groups (Ambulant and wheelchair-bound Duchenne muscular dystrophy
      patients, myotonic dystrophy patients, and patients with Charcot-Marie-Tooth
      neuropathy). The responsiveness indices showed that the change in activity
      measures was higher in patients who reported deteriorated functional status and
      in patients with Duchenne muscular dystrophy. The ACTIVLIM questionnaire showed a
      good sensitivity to change and could be useful in research settings to
      characterize the disease course of NMD.

PMID- 19167890
TI  - Eosinophilic myositis as presenting symptom in gamma-sarcoglycanopathy.
AB  - The patient reported here presented with first symptoms at the age of 10 showing
      an abnormal gait, calf hypertrophy and winged scapulae. She was diagnosed with
      eosinophilic myositis after muscle biopsy. A second muscle biopsy at the age of
      20 and subsequent genetic testing, however, revealed the underlying condition of
      a primary gamma-sarcoglycanopathy, or LGMD2C. To our knowledge, this is the first
      LGMD2C patient reported who initially presented with eosinophilic myositis.
      Eosinophilia has been reported previously in patients with Calpainopathy and
      Becker Muscular Dystrophy and might be an early, but transient feature of a wider
      range of muscular dystrophies.

PMID- 19167891
TI  - Test-retest reliability [corrected] of center of pressure measures of postural
      stability during quiet standing in a group with musculoskeletal disorders
      consisting of low back pain, anterior cruciate ligament injury and functional
      ankle instability.
AB  - Reliability is a population-specific property, but to the authors' knowledge
      there has been no study to determine the test-retest reliability of the postural
      stability measures such as center of pressure (COP) measures in the population of
      patients with musculoskeletal disorders (MSDs), while their clinical applications
      have been presented in literature. So, 33 patients with low back pain (LBP),
      anterior cruciate ligament (ACL) injury and functional ankle instability (FAI)
      randomly completed postural measurements with three levels of difficulty (rigid
      surface-eyes open, rigid surface-eyes closed, and foam surface-eyes closed) in
      two sessions. COP data were used to calculate standard deviation of amplitude,
      standard deviation of velocity, phase plane portrait, mean total velocity and
      area (95% confidence ellipse). Relative reliability of these measures was
      assessed using intraclass correlation coefficient (ICC) and absolute reliability
      using standard error of measurement (SEM) and coefficient of variation (CV).
      Also, minimal metrically detectable change (MMDC) was calculated to quantify
      intervention effects. Among different COP parameters, mean total velocity in all
      conditions of postural difficulty showed high to very high reliability, with ICC
      range of 0.74-0.91, SEM range of 0.09-0.40cm/s, CV range of 5.31-8.29% and MMDC
      range of 0.19-0.79cm/s. Phase plane portrait in anteroposterior-mediolateral (AP
      ML) and ML direction were other best parameters with respect to the level of
      reliability. Mean total velocity and phase plane portrait parameters are
      suggested as good candidates to use for quantification and assessment of balance
      performance and identifying those with MSDs.

PMID- 19167892
TI  - Design, synthesis and biological evaluation of a novel class of anticancer
      agents: anthracenylisoxazole lexitropsin conjugates.
AB  - The synthesis and in vitro anti-tumor 60 cell lines screen of a novel series of
      anthracenyl isoxazole amides (AIMs) (While not a strict acronym, the designation
      AIM is in honor of the memory of Professor Albert I. Meyers.) (22-33) are
      described. The molecules consist of an isoxazole that pre-organizes a planar
      aromatic moiety and a simple amide and/or lexitropsin-oligopeptide. The new
      conjugate molecules were prepared via doubly activated amidation modification of
      Weinreb's amide formation technique, using SmCl(3) as an activating agent which
      produces improved yields for sterically hindered 3-aryl-4-isoxazolecarboxylic
      esters. The results of the National Cancer Institute's (NCI) 60 cell line
      screening assay show a distinct structure activity relationship (SAR), wherein a
      trend of the highest activity for molecules with one N-methylpyrrole peptide.
      Evidence consistent with a mechanism of action via the interaction of these
      compounds with G-quadruplex (G4) DNA and a structural based rational for the
      observed selectivity of the AIMs for G4 over B-DNA is presented.

PMID- 19167893
TI  - 13-Methyl-substituted des-C,D analogs of (20S)-1alpha,25-dihydroxy-2-methylene-19
      norvitamin D3 (2MD): synthesis and biological evaluation.
AB  - Analogs of (20S)-1alpha,25-dihydroxy-2-methylene-19-norvitamin D(3) (2, 2MD),
      substituted at C-13 but lacking both C and D rings, were prepared in convergent
      syntheses, starting with the chiral ester 14 and the phosphine oxide 29. Two of
      the synthesized vitamins (11 and 32) were analogs in which the 13-methyl group
      constituted a substituent of an unsaturated fragment, that is, C(13)-C(17) double
      bond, whereas in the two other cases (12 and 13), the methyl group belonged to a
      ternary carbon stereogenic center. The aim of these studies was to further
      explore extensive modifications in the 'upper' part of the vitamin D skeleton in
      the hope of finding biologically active analogs of potential therapeutic value.
      The commercial (R)-(-)-methyl-3-hydroxy-2-methylpropionate (14) was converted in
      six steps to alcohol 18, the vitamin D side chain fragment. Its subsequent three
      step transformation led to aldehyde 20 which was subjected to the Still-Gennari
      HWE reaction with anion derived from ester 21. The obtained alpha,beta
      unsaturated esters 22 and 23 served as convenient starting compounds to the
      syntheses of the corresponding chiral acyclic aldehydes, beta,gamma-unsaturated
      (28) and saturated (39 and 40), required for the final Wittig-Horner coupling
      with the anion of the phosphine oxide 29. After hydroxyl deprotection, the
      synthesized vitamin D analogs 11-13 and 32 were purified and biologically tested.
      Only the (13R,20S)-analog 12 retained substantial, although 30 times lower than
      1alpha,25-(OH)(2)D(3), binding ability to the full-length rat recombinant vitamin
      D receptor (VDR). This analog was also very effective in differentiation of HL-60
      cells, and it exerted significant transcriptional activity (2 times and 15 times
      less potent, respectively, as compared to the native hormone). The in vivo tests
      showed that all synthesized vitamin D analogs were devoid of calcemic activity.

PMID- 19167894
TI  - Importance of surface properties of affinity resin for capturing a target
      protein, cyclooxygenase-1.
AB  - We have prepared affinity resins based on two kinds of solid phases, including a
      commercially available solid phase, to re-realize the importance of surface
      properties of affinity resins such as controlled ligand density as well as
      existential surroundings of the ligand. Affinity resins were prepared using non
      steroidal anti-inflammatory drugs, such as Ketoprofen, Ibuprofen, and Aspirin,
      having different activities as ligands. The ligand density was controlled through
      two different strategies: one strategy was that the solid phases having different
      amino group densities (20, 60, 100, 125 micromol/ml) were utilized then,
      Ketoprofen was fully immobilized through condensation reaction to amino groups;
      another strategy was that a solid phase having amino group density (125
      micromol/ml) was utilized then, each ligand was immobilized with controlled
      immobilization rate. In addition, a typical hydrophobic group, stearoyl group
      (C(18) group), was immobilized on the affinity resin with controlled ligand
      immobilization rate to change the existential surroundings of the ligand.
      Affinity tests were performed for Cyclooxgenase-1 (COX-1) as it was the target
      protein in this work. The amount of captured COX-1 was evaluated utilizing each
      affinity resin. It was suggested that the density of surface ligand tends to
      relate to the amount of captured COX-1 on our solid phase-based affinity resins;
      however, several exceptions occurred according to the surface properties of
      affinity resins in the case of commercial one.

PMID- 19167895
TI  - Aryldiones incorporating a [1,4,5]oxadiazepane ring. Part I: Discovery of the
      novel cereal herbicide pinoxaden.
AB  - Derivatives of the new class of 3-hydroxy-4-phenyl-5-oxo-pyrazolines were
      optimized towards both herbicidal activity on key annual grass weed species and
      selectivity in small grain cereal crops. The generic structure can be separated
      into three parts for the analysis of the structure-activity relationships, namely
      the aryl, the dione with its prodrug forms and the hydrazine moiety. Each area
      appears to play distinct and different roles in overall expression of biological
      performance which is further beneficially influenced by adjuvant response and
      safener action. Pinoxaden 6, a novel graminicide for use in wheat and barley
      incorporating a [1,4,5]oxadiazepane ring, eventually emerged as a development
      candidate from the discovery and optimization process.

PMID- 19167896
TI  - Stereoselective synthesis of bioactive isosteviol derivatives as alpha
      glucosidase inhibitors.
AB  - Considerable interest has been attracted in isosteviol and its derivatives
      because of their large variety of pharmacological activities. In this project, a
      series of novel compounds containing hydroxyl, hydroxymethyl group and heteroatom
      containing frameworks fused with isosteviol structure were synthesized and
      evaluated as alpha-glucosidase inhibitors, aimed at clarifying the structure
      activity correlation. The results indicated that these isosteviol derivatives
      were capable of inhibiting in vitro alpha-glucosidase with moderate to good
      activities. Among them, indole derivative 15b exhibited the highest activities
      and thus may be exploitable as a lead compound for the development of potent
      alpha-glucosidase inhibitors.

PMID- 19167897
TI  - Three-dimensional characterization of drug-encapsulating particles using STEM
      detector in FEG-SEM.
AB  - New drug-encapsulating particles were investigated using bright field (BF)
      scanning transmission electron microscopy (STEM) in a field emission gun (FEG)
      scanning electron microscope (SEM). Thickness characterization was done based on
      measuring the effective cross-section for interaction in our sample-detector
      configuration using calibration particles. A simplified analytical model, taking
      account of BF-STEM contrast and effective cross-section for interaction, was
      utilized for transforming projected two-dimensional BF-STEM images into three
      dimensional thickness images. The three-dimensional characterization is
      demonstrated on a new family of biological materials composed of submicron to
      micron drug-free and drug-encapsulating particles. The importance of using BF
      STEM in SEM, relative to other electron microscopy methods, is discussed as well
      as the lateral and depth resolution.

PMID- 19167898
TI  - Study of the excitation function for the deuteron induced reaction on 64Ni(d,2n)
      for the production of the medical radioisotope 64Cu.
AB  - The production of (64)Cu, a radioisotope of considerable interest for the
      application in nuclear medicine for PET imaging and radioimmunotherapy, was
      investigated by deuteron bombardment of enriched (64)Ni target up to E(d)=20.5
      MeV. The experimental excitation function for the reaction (64)Ni(d,2n)(64)Cu was
      measured using the stacked foil irradiation technique followed by HPGe gamma-ray
      analysis at 1346 keV and is compared with earlier literature values. Cross
      section data for the (64)Ni(d,p)(65)Ni reaction are determined for the first
      time. Thick target yields are derived and compared with results of other
      production routes.

PMID- 19167899
TI  - Distribution of radionuclides in soil samples from a petrified wood forest in El
      Qattamia, Cairo, Egypt.
AB  - The concentrations and distribution of radionuclides in a petrified wood forest
      in El-Qattamia have been determined using high-resolution gamma spectrometry to
      evaluate the environmental radioactivity. The mean activity concentrations of
      (238)U, (232)Th and (40)K were 65.26+/-12.99, 23.66+/-0.95 and 146.33+/-1.50 Bq
      kg(-1), respectively. Data of the soil samples show evidence of possible
      deposition and accumulation of (137)Cs. The mean activity concentration of
      (137)Cs in the soil samples was 4.37+/-0.16 Bq kg(-1) with a range of 0.00-35.70
      Bq kg(-1). The measured activity concentration range of (137)Cs was compared with
      reported ranges in the literature from some of the other locations in the world.
      The radium-equivalent, dose rate in air and annual effective dose rate were
      evaluated. The mean activity concentrations of the gamma-ray emissions from
      radionuclides in El-Qattamia petrified wood forest region were relatively low.

PMID- 19167900
TI  - Delayed leaf senescence by exogenous lyso-phosphatidylethanolamine: towards a
      mechanism of action.
AB  - Exogenous application of the lysophospholipid, lyso-phosphatidylethanolamine
      (LPE) is purported to delay leaf senescence in plants. However, lyso
      phospholipids are well known to possess detergent-like activity and application
      of LPE to plant tissues might be expected to rather elicit a wound-like response
      and enhance senescence progression. Since phosphatidic acid (PA) accumulation and
      leaf cell death are a consequence of wounding, PA- and hormone-induced senescence
      was studied in leaf discs from Philodendron cordatum (Vell.) Kunth plants in the
      presence or absence of egg-derived 18:0-LPE and senescence progression quantified
      by monitoring both lipid peroxidation (as the change in malondialdehyde
      concentration), and by measuring retention of total chlorophyll (Chl(a+b)) and
      carotenoids (C(c+x)). Only abscisic acid (ABA) stimulated lipid peroxidation
      whereas ABA, 1-aminocyclopropane-1-carboxylic acid (ACC), the immediate precursor
      to ethylene (ETH), and 16:0-18:2-PA stimulated loss of chloroplast pigments.
      Results using primary alcohols as attenuators of the endogenous PA signal
      confirmed a role for PA as an intermediate in both ABA- and ETH-mediated
      senescence progression. Exogenous 18:0-LPE did not appear to influence senescence
      progression and was unable to reverse hormone-induced senescence progression.
      However, when supplied together with 16:0-18:2-PA at 1:1 (mol:mol), activity of
      phosphatidylglycerol (PG) hydrolase, chlorophyllase (E.C. 3.1.1.14), and
      progression of leaf senescence were negated. This apparent anti-senescence
      activity of exogenous 18:0-LPE was associated with induction of the pathogenesis
      related protein, extracellular acid invertase (Ac INV, E.C. 3.2.1.26) suggesting
      that 18:0-LPE like 16:0-18:2-PA functions as an elicitor.

PMID- 19167901
TI  - Enhanced determination of abscisic acid (ABA) and abscisic acid glucose ester
      (ABA-GE) in Cistus albidus plants by liquid chromatography-mass spectrometry in
      tandem mode.
AB  - An improved, quick and simple method for the extraction and quantification of the
      phytohormones (+)-abscisic acid (ABA) and its major glucose conjugate, abscisic
      acid glucose ester (ABA-GE) in plant samples is described. The method includes
      the addition of deuterium-labeled internal standards to the leaves at the
      beginning of the extraction for quantification, a simple
      extraction/centrifugation process and the injection into the liquid
      chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS)
      system in multiple reaction monitoring mode (MRM). Quality parameters of the
      method (detection limits, repeatability, reproducibility and linearity) have been
      studied. The objective of this work is to show the applicability of this method
      for quantifying the endogenous content of both ABA and ABA-GE in Cistus albidus
      plants that have been grown during an annual cycle under Mediterranean field
      conditions. Leaf samples from winter plants have low levels of ABA which increase
      in spring and summer showing two peaks that corresponded to April and August.
      These increases are coincident with the high temperature and solar radiation and
      the low RWC and RH registered along the year. On the other hand, the endogenous
      levels of ABA-GE increase until maximum values in July just before the ABA
      content reaches its highest concentration, decreasing in August and during autumn
      and winter. Our results suggest that the method is useful for quantifying both
      compounds in this plant material and represents the advantage of a short-time
      sample preparation with a high accuracy and viability.

PMID- 19167902
TI  - Enzymes that control the thiamine diphosphate pool in plant tissues. Properties
      of thiamine pyrophosphokinase and thiamine-(di)phosphate phosphatase purified
      from Zea mays seedlings.
AB  - The pool of thiamine diphosphate (TDP), available for TDP-dependent enzymes
      involved in the major carbohydrate metabolic pathways, is controlled by two
      enzyme systems that act in the opposite directions. The thiamine
      pyrophosphokinase (TPK) activates thiamine into TDP and the numerous phosphatases
      perform the reverse two-step dephosphorylation of TDP to thiamine monophosphate
      (TMP) and then to free thiamine. Properties and a possible cooperation of those
      enzymes in higher plants have not been extensively studied. In this work, we
      characterize highly purified preparations of TPK and a TDP/TMP phosphatase
      isolated from 6-day Zea mays seedlings. TPK was the 29-kDa monomeric protein,
      with the optimal activity at pH 9.0, the K(m) values of 12.4microM and 4.7mM for
      thiamine and ATP, respectively, and the V(max) value of 360pmol TDPmin(-1)mg(-1)
      protein. The enzyme required magnesium ions, and the best phosphate donor was
      GTP. The purified phosphatase was the dimer of 24kDa subunits, showed the optimal
      activity at pH 5.0 and had a rather broad substrate specificity, although TDP,
      but not TMP, was one of the preferable substrates. The K(m) values for TDP and
      TMP were 36microM and 49microM, respectively, and the V(max) value for TDP was
      significantly higher than for TMP (164 versus 60nmolesmin(-1)mg(-1) protein). The
      total activities of TPK and TDP phosphatases were similarly decreased when the
      seedlings were grown under the illumination, suggesting a coordinated regulation
      of both enzymes to stabilize the pool of the essential coenzyme.

PMID- 19167903
TI  - Assessment of hepatosplanchnic pathophysiology during thoracoabdominal aortic
      aneurysm repair using visceral perfusion and shunt.
AB  - OBJECTIVE: Despite the recognition of importance to avoid visceral ischemia
      during thoracoabdominal aortic aneurysm (TAAA) repair, the methodology of
      visceral perfusion seems still controversial and its pathophysiology has not been
      clearly understood. We investigated hepatosplanchnic metabolism during visceral
      perfusion/shunt in TAAA repair. METHODS: Seventeen patients (10 male, 64+/-15
      years old) who underwent elective TAAA repair using visceral perfusion/shunt
      under mild hypothermic distal aortic perfusion were retrospectively enrolled.
      Their aneurysm extension was type I and II in eight patients. In seven patients,
      four visceral arteries were perfused through a side-arm of distal aortic
      perfusion, while they were perfused by an independent pump in another five
      patients. In four of these 12 (two in each technique), visceral perfusion was
      converted into selective shunt after completion of aortic anastomosis. In the
      remaining five patients, four branches were initially perfused through a side-arm
      of distal aortic perfusion, and aortic perfusion was subsequently stopped after
      completion of aortic anastomosis. Hepatic venous oxygen saturation (ShO(2)),
      oxygen and lactate extraction ratio (OER, LER), and arterial ketone body ratio
      (AKBR) were measured at six time points. RESULTS: There was no mortality,
      liver/renal dysfunction, or spinal cord injury. Two patients required re
      exploration for bleeding. Fourteen patients were extubated within 24h
      postoperatively. Mean intensive care unit stay was 2.3+/-1.7 days. During
      visceral perfusion, OER raised (31+/-13% to 68+/-21%, p=0.0012) and ShO(2)
      decreased (67+/-12% to 34+/-24%, p=0.0026) significantly. They recovered to
      baseline at skin closure. During the same period, LER (41+/-22% to -1+/-34%,
      p=0.0035) and AKBR (0.47+/-0.13 to 0.20+/-0.08, p=0.0012) significantly
      decreased. AKBR recovered to baseline at skin closure, but LER did not. ShO(2)
      (R(2)=0.483, p=0.0257) and LER (R(2)=0.774, p=0.0018) at skin closure and LER
      after initiation of partial cardiopulmonary bypass (R(2)=0.427, p=0.0211) had
      significant correlation with postoperative peak serum bilirubin level. AKBR after
      initiation of partial cardiopulmonary bypass had significant correlation with
      postoperative peak serum alanine aminotransferase level (R(2)=0.289, p=0.0476).
      CONCLUSIONS: Visceral perfusion/shunt in TAAA repair may avoid critical
      irreversible hepatosplanchnic ischemia but provide unphysiological blood flow to
      the liver and thus should be shortened.

PMID- 19167904
TI  - Everolimus attenuates neointimal hyperplasia in cultured human saphenous vein
      grafts.
AB  - OBJECTIVE: Neointimal hyperplasia is the first step in a cascade leading to a
      reduced patency rate of saphenous vein grafts in comparison to arterial grafts in
      coronary artery bypass grafting. Using cultured human saphenous vein grafts as a
      model for coronary artery bypass grafting, we investigated if the mammalian
      target of rapamycin inhibitor everolimus attenuates neointimal hyperplasia.
      METHODS: Saphenous vein grafts from 10 patients undergoing coronary artery bypass
      grafting were processed as follows: from each patient, one segment served as
      baseline control at day 0. Two segments were cultured in a neointimal hyperplasia
      model separately. One received no treatment and the other everolimus (1 microM).
      All vein grafts underwent histomorphometric analysis, assessment of proliferation
      by Ki-67 immunostaining and quantification of phospho-S6 ribosomal protein using
      western blot analysis. RESULTS: Everolimus treatment resulted in reduced
      neointimal hyperplasia (thickness 3.7+/-1.2 microm) compared to untreated
      controls (10.1+/-2.5 microm, p=0.008). The intima/intima+media-ratio was reduced
      in the everolimus group (0.10+/-0.02) compared to untreated controls (0.24+/
      0.07, p=0.008). The number of Ki-67 positive proliferating cells in everolimus
      treated vein grafts (15+/-7 cells/high power field) showed a tendency of
      reduction compared to untreated controls (36+/-20 cells/high power field,
      p=0.036). Finally, everolimus treatment resulted in downregulation of S6
      ribosomal protein phosphorylation in comparison to untreated controls.
      CONCLUSION: Everolimus is able to reduce neointimal proliferation in cultured
      human saphenous vein grafts by inhibition of the mammalian target of rapamycin,
      even though different transfection methods are to be evaluated for a clinical
      application in coronary artery bypass grafting.

PMID- 19167905
TI  - Editorial comment: Quality measurement in adult cardiac surgery: a challenge.

PMID- 19167906
TI  - Routine underwater seal drains are not required after transthoracic
      oesophagectomy: a pilot study.
AB  - OBJECTIVE: Underwater seal drainage of the pleural cavity has been standard
      practice after transthoracic oesophagectomy. However these chest tubes cause pain
      and hamper mobility, thereby causing significant morbidity and delaying recovery.
      We postulated that if complete lung expansion and optimum pulmonary function
      could be achieved and maintained following a transthoracic oesophagectomy using
      simple gravity aided transabdominal tube drainage of the pleural cavity, then
      these may be a simpler alternative to the conventional underwater seal chest
      drains. METHODS: A total of 50 patients had transthoracic oesophagectomy for
      oesophageal cancer. Of the cohort, 44 patients were fitted with the
      transabdominal drain described and hence had 'modified pleural drainage'
      following the oesophagectomy. All patients had a posterior mediastinal drain
      placed in either the right or the left pleural cavity during the oesophagectomy.
      The tube drain was inserted into the pleural cavity from the abdomen and placed
      into the desired position across the diaphragmatic hiatus. The drain was managed
      in the conventional manner and patients were monitored postoperatively for any
      developing pleural collections through serial chest X-rays. Respiratory function
      was closely monitored. RESULTS: The drains were removed without any significant
      respiratory complications by the 8th postoperative day in 86% of the patients.
      Only three patients (7%) developed clinically significant recurrent pleural
      effusions, causing respiratory compromise meriting further drainage. This was
      easily and safely managed using fine bore pigtail drains inserted under
      ultrasound guidance. CONCLUSION: Transabdominal gravity aided tube drainage of
      the mediastinum and the pleural cavity is an effective and safe means of draining
      the chest, following uncomplicated transthoracic oesophagectomy.

PMID- 19167907
TI  - Carbon bio-fixation by photosynthesis of Thermosynechococcus sp. CL-1 and
      Nannochloropsis oculta.
AB  - There is a great potential to assimilate CO(2) and produce bio-energy from
      cellular component by utilizing carbon fixation of photosynthetic microorganisms.
      Two different types of photosynthetic microorganisms were used in the present
      study. The strain Thermosynechococcus sp. CL-1 (TCL-1) was previously isolated
      from a hot spring while Nannochloropsis sp.Oculta (NAO) from sea water. Two types
      of inorganic carbon were used (gaseous CO(2) and dissolved inorganic carbon, DIC)
      with nitrate as N source under different temperature conditions. The Monod model
      was used to relate its growth rate and DIC concentration. Additionally, lipid and
      carbohydrate of cell component, which can be used as bio-energy precursors, as
      function of CO(2) and DIC concentrations is quantified. The growth rate of TCL-1
      decreased as CO(2) concentrations increased from 10% to 40% due to low pH
      inhibition with the maximum value 2.7 d(-1) at 10% CO(2). As for NAO, the maximum
      growth rate of about 1.6 d(-1) was obtained at 5% and 8% CO(2) (pH between 5.5
      and 7 at 30 degrees C). Regarding the cultivation of TCL-1 under various DIC
      concentrations, the maximum growth rate of TCL-1 was 3.5 d(-1) at the initial DIC
      94.3 mM, pH 9.5 and 50 degrees C. The carbohydrate content of TCL-1 increased
      from 2.1% to 33% as DIC concentration increased from 4.7 to 94.3 mM. However, the
      33% carbohydrate content at 94.3 mM DIC was much less than 61% at 10% CO(2). That
      may be due to the fact that the cultivation at 94.3 mM DIC can not supply
      adequate amounts of DIC to produce carbohydrate under N-limiting conditions.
      Conversely, enough amounts of DIC supplied from washing flue gas for cultivating
      TCL-1 would provide a higher performance of carbon bio-fixation and carbohydrate
      production.

PMID- 19167908
TI  - The role of natriuretic peptide administration in cardiovascular surgery
      associated renal dysfunction: a systematic review and meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVE: Randomized controlled trials involving natriuretic peptide
      administration in the perioperative cardiovascular setting have shown
      inconsistent effects for renal and other clinical endpoints. The authors aimed to
      systematically review these trials to ascertain the role of natriuretic peptide
      administration in the management of cardiovascular surgery-associated renal
      dysfunction. DESIGN: A systematic review and meta-analysis. SETTING: A hospital.
      PARTICIPANTS: A total of 934 adult patients from 13 randomized controlled trials.
      INTERVENTIONS: Natriuretic peptides. MEASUREMENTS AND MAIN RESULTS: MEDLINE,
      EMBASE, Cochrane Renal Health Library, and Google scholar were searched
      independently by 2 reviewers for randomized controlled studies comparing
      natriuretic peptides with placebo in patients undergoing cardiovascular
      surgeries. Studies reporting data on renal outcomes were included. Two reviewers
      independently assessed the studies for eligibility and extracted the relevant
      data. The pooled estimate showed that natriuretic peptide administration was
      associated with a reduction in acute renal failure requiring dialysis (odds ratio
      = 0.32 [0.15-0.66]) and a statistically nonsignificant trend toward a reduction
      in 30-day or in-hospital mortality (odds ratio = 0.59 [0.31-1.12]). Other
      benefits were a reduction in postsurgery peak serum creatinine levels, an
      increase in postsurgery urine output, a reduction in postsurgery serum
      aldosterone levels, and reductions in mechanical ventilation duration and
      intensive care unit stay length. Most of the included studies addressing this
      topic were small and lacked adequate power to reach statistical significance on
      their own. CONCLUSIONS: Current literature analyzing studies evaluating the
      administration of natriuretic peptides in cardiovascular surgery may be
      associated with significant improvements in clinical outcomes. Given the
      limitations of meta-analysis, these observations need to be confirmed in a
      larger, adequately powered, prospective multicenter study.

PMID- 19167909
TI  - Intraoperative graft patency verification in coronary artery surgery: modern
      diagnostic tools.

PMID- 19167910
TI  - A randomized trial of outcomes of anesthetic management directed to very early
      extubation after cardiac surgery in children.
AB  - OBJECTIVES: Intraoperative management directed to early extubation of children
      undergoing cardiac surgery has been suggested as a viable alternative to
      prolonged postoperative mechanical ventilation. The authors evaluated the safety
      and efficacy of this approach in a randomized prospective trial. DESIGN: A
      prospective randomized observational study. SETTING: A single university
      affiliated hospital. PARTICIPANTS: One hundred consecutive pediatric patients
      (age 1 month-15 years, weight 3.0-51 kg) requiring cardiac surgery. Patients
      younger than 1 month of age and those requiring mechanical ventilation before the
      operation were considered ineligible for the study. INTERVENTIONS: Patients were
      randomly allocated to a group with anesthetic management and extubation in the
      operating room (early group [EG]) and a group with elective prolonged mechanical
      ventilation (control group [CG]). MEASUREMENTS AND MAIN RESULTS: A difference in
      outcome as reflected by the pediatric intensive care unit (PICU) and hospital
      lengths of stay and postoperative morbidity and mortality was analyzed. A
      separate analysis was performed in children younger than 3 years old. The
      extubation time in the CG was 25.0 +/- 26.9 hours. No differences in mortality,
      the need for re-exploration for bleeding, the need for reintubation, the
      incidence of abnormal chest radiographic findings, or cardiac and septic
      complications between groups were found. PICU and postoperative hospital lengths
      of stay were significantly shorter in patients in the EG (3.3 +/- 1.9 days in the
      EG v 5.8 +/- 4.1 in the CG, p < 0.001, and 7.4 +/- 2.9 days in the EG v 11.2 +/-
      6.8 days in the CG, p = 0.009). CONCLUSIONS: In children undergoing cardiac
      surgery, anesthetic management with early cessation of mechanical ventilation
      appears to be safe and decreases hospital and PICU length of stay. However,
      because the size of the study did not allow for the detection of possible
      differences in perioperative mortality, only a large multicenter study may
      provide a definite answer to this question. The present study may be treated as a
      pilot for such a trial.

PMID- 19167911
TI  - A novel use of the air regulator used for spraying fibrin glue in the operating
      room.

PMID- 19167912
TI  - B-type natriuretic peptide as a predictor of postoperative heart failure after
      aortic valve replacement.
AB  - OBJECTIVE: B-type natriuretic peptide (BNP) has been established as a biomarker
      for heart failure. The objective was to evaluate BNP measured on arrival in the
      intensive care unit (ICU) as a predictor for heart failure defined as need for
      inotropic support or IABP beyond 24 hours postoperatively after aortic valve
      replacement. DESIGN: A prospective, observational study. SETTING: A
      cardiothoracic surgery unit at a tertiary level hospital. PARTICIPANTS: One
      hundred sixty-one patients undergoing aortic valve replacement. MEASUREMENTS AND
      MAIN RESULTS: Two levels of BNP were evaluated: the median (BNP >133 pg/mL) and a
      cutoff (BNP >82 pg/mL) based on receiver-operating characteristic (ROC) analysis.
      Uni- and multivariate analysis were performed to identify predictors of
      postoperative heart failure. Patients with postoperative heart failure (n = 37)
      showed a more than 10-fold increase in 30-day mortality (8.1%, 3/37) compared
      with patients without postoperative heart failure (0.8%, 1/124) (p = 0.038).
      Elevated postoperative BNP levels were identified as an independent predictor of
      postoperative heart failure: BNP >82 pg/mL (p = 0.004) and BNP >133 pg/mL (p =
      0.013). The area under the ROC curve for BNP as a predictor of postoperative
      heart failure was 0.69. CONCLUSION: Postoperative heart failure after aortic
      valve replacement is still a very serious condition with increased early
      mortality. The results of the present study suggest that an elevated BNP level on
      arrival in the ICU is an independent predictor of postoperative heart failure
      after aortic valve replacement. In the authors' opinion, an increased BNP level
      on arrival in the ICU may support early diagnosis and allow optimal management of
      heart failure after aortic valve replacement.

PMID- 19167915
TI  - Lipid metabolism and hyperlipidemia in dogs.
AB  - Lipid metabolism in dogs can be divided into exogenous and endogenous pathways
      and exhibits some unique characteristics compared to other species.
      Hyperlipidemia is common in dogs, and can be either primary or secondary to other
      diseases. Secondary hyperlipidemia is the most common form and can be a result of
      endocrine disorders, pancreatitis, cholestasis, protein-losing nephropathy,
      obesity, and high fat diets. Primary hyperlipidemia is less common and usually
      associated with certain breeds. Hypertriglyceridemia of Miniature Schnauzers is
      the most common type of primary hyperlipidemia in dogs in the United States, and
      appears to have a genetic basis although its etiology remains unknown. Possible
      complications of canine hyperlipidemia include pancreatitis, liver disease,
      atherosclerosis, ocular disease, and seizures. Management is achieved by
      administration of low fat diets with or without the administration of lipid
      lowering agents such as omega-3 fatty acids, gemfibrozil, and niacin.

PMID- 19167913
TI  - Desflurane-induced cardioprotection against ischemia-reperfusion injury depends
      on timing.
AB  - OBJECTIVES: The authors tested the hypothesis that desflurane-induced
      cardioprotection depends on the timing of application and whether desflurane
      induced postconditioning is mediated by nitric oxide. DESIGN: A prospective
      randomized vehicle-controlled study. SETTING: A university research laboratory.
      SUBJECTS: New Zealand White rabbits (N = 56). INTERVENTIONS: Rabbits were
      instrumented and subjected to a 30-minute coronary artery occlusion (CAO) and 3
      hours of reperfusion. Animals were randomized to 8 groups (n = 7) and received
      0.0 or 1.0 minimum alveolar concentration desflurane for 30 minutes before CAO
      (PRE), during CAO (ISCH), after CAO (POST), before and after CAO (PRE + POST), or
      continuously for 90 minutes starting 30 minutes before CAO (PRE + ISCH + POST).
      In 2 separate experimental groups, the nitric oxide synthase inhibitor N-omega
      nitro-L-arginine (L-NA) was administered before reperfusion in the presence or
      absence of desflurane. Data are mean +/- standard deviation. RESULTS: Infarct
      size was 68% +/- 14% in control experiments. Desflurane significantly (p < 0.05)
      reduced infarct size in the PRE (43% +/- 9%) and POST groups (49% +/- 12%) but
      not in the ISCH group (69% +/- 9%). The PRE + ISCH + POST and PRE + POST groups
      produced similar reductions in infarct size to 47% +/- 12% and 43% +/- 9%,
      respectively. L-NA alone had no effect on infarct size (61% +/- 9%) but blocked
      postconditioning completely (L-NA + POST, 68% +/- 10%). CONCLUSIONS: Desflurane
      induces pre- and postconditioning but does not confer cardioprotection during
      ischemia in rabbits. The combination of pre- and postconditioning or continuous
      application does not provide additional cardioprotection. Furthermore, desflurane
      induced postconditioning is mediated by nitric oxide.

PMID- 19167916
TI  - Is hyperlipidemia clinically important in dogs?

PMID- 19167917
TI  - Molecular modeling of ligand-receptor interactions in GABA C receptor.
AB  - A new homology model of the GABA binding site of the GABA(C) receptor was built.
      Natural agonist GABA and antagonist TPMPA were docked into the receptor and
      molecular dynamics simulation of the complexes was performed to clarify binding
      poses of the ligands. It was shown that orientation of the ligand is defined by
      salt bridges between the ligand and the arginine (Arg104) and glutamate residues
      (Glu194 and Glu196) of the binding site. Different behavior and binding poses for
      agonist and antagonist was demonstrated by molecular dynamics simulation along
      with differential movement of the loop C during agonist and antagonist binding.
      Binding orientations of the ligands revealed that main binding forces in the GABA
      binding site should be electrostatic ones.

PMID- 19167918
TI  - In vivo dosimetry during DSA of the carotid and renal arteries. Deriviation of
      local DRLs.
AB  - The Euratom directive 97/43 recommends the use of patient dose surveys in
      diagnostic radiology and the establishment of diagnostic reference dose levels
      (DRLs). The aims of this study are to perform measurements of the entrance
      surface dose (ESD) during diagnostic digital subtraction angiography (DSA) of the
      renal and carotid arteries using thermoluminescence dosemeters (TLDs), extraction
      of local DRLs, and calculation of the effective dose. Dose measurement for the
      staff was also performed. Dose measurements were performed on 48 participating
      patients. The mean effective dose was calculated to be 15.9 mSv and 8.9 mSv, for
      the renal and carotid DSA, respectively. The effective dose of the radiologist
      was calculated to be 0.022 mSv and 0.023 mSv per procedure for renal and carotid
      DSA respectively, when wearing a protective apron and using a movable ceiling
      mounted shield. Radiation dose variation depends on the physical characteristics
      of the patient, on the procedure preferences by radiologists and on the
      difficulties in conducting the procedures. The lack of DRLs for the specific
      examinations lead the research team to choose the DRL for DSA of the renal
      arteries to be 169 mGy for ESD at the pelvic region and for DSA of the carotid
      arteries to be 313 mGy for ESD at the region of the aortic arc.

PMID- 19167919
TI  - [Is pelvic irradiation still justified in the treatment of prostate cancer by
      exclusive radiotherapy?].
AB  - Prostate cancer is associated with a risk of lymph node involvement, which
      increases with clinical stage, Gleason score, and PSA level at diagnosis. When
      this risk is higher than 15%, it has been suggested to irradiate the pelvis in
      addition to the prostate despite an increased risk of gastrointestinal
      toxicities. However, several randomized trials seem to call into question this
      therapeutic approach. This review presents the potent role of pelvic irradiation
      in the treatment of locally advanced prostate cancer treated with exclusive
      radiotherapy.

PMID- 19167920
TI  - [Hypofractionated breast radiotherapy in 13 fractions, perfect tolerance or
      delayed early reaction? Prospective study of Curie Institute].
AB  - PURPOSE: To assess the skin toxicity of this scheme and the time to its
      appearance. PATIENTS AND METHODS: Eighty-one prospectively recorded patients
      (pts), treated in Radiotherapy Department for Breast Cancer (BC) with
      radiotherapy (RT) to the whole breast at the dose of 42.9Gy per 13 fractions (F)
      per 5 weeks have been studied. Skin reactions were monitored weekly using the
      National Cancer Institute-Common Toxicity Criteria scoring system, version 3. All
      risk factors as tobacco smoking, diabetes, obesity were also recorded. RESULTS:
      All 81 pts, aged from 40 to 83 years (median: 70 years) received whole breast RT
      42.9Gy per 13 F without lymph node irradiation after breast conserving surgery.
      There were no pts with concurrent chemo- and/or hormonal therapy. Seventeen
      patients (21%) have been treated using decubitus dorsal (DD) technique and 64
      (79%) using the previously described isocentric decubitus lateral (IDL)
      technique. During the RT, only 34 pts (42%) experienced grade I skin reactions
      and 47 pts (58%) were without. At the last day of the breast irradiation, there
      were 66 (81%) grade I (N=59) and II (N=7) skin reactions and 15 pts (19%)
      without. The early skin tolerance of this scheme was considered to be excellent.
      But in the 2 weeks after the RT, 20 pts (25%) asked for new clinics with their
      radiation oncologist as a matter of urgency due to worsening of their skin
      condition. All of them have been seen by their physician and/or the nurse. Of
      them, nine presented grade I and 11 presented grade II skin reactions, with
      necessity of special skin care. The analysis of these results was realized and
      delayed clinics were organized for all pts treated with this scheme 10-14 days
      after the end of the radiation treatment. CONCLUSIONS: The breast RT 42.9Gy/13 F
      have been previously described as an efficacious and well tolerated scheme. This
      prospective homogeneous group of patients showed that delayed early skin
      reactions could appear in some cases. Therefore complementary clinics are needed
      to detect and treat these reactions.

PMID- 19167921
TI  - The integration of chemoradiation in the care of patient with localized
      pancreatic cancer.
AB  - The use of chemoradiation for patients with localized pancreatic cancer is
      controversial. Although some randomized trials have indicated that chemoradiation
      improves the median survival of patients with locally advanced as well as
      resected pancreatic cancer, other more recent trials have called into question
      the role of chemoradiation and have supported the use of chemotherapy. In the
      adjuvant setting, the high local tumor recurrence/persistence rate in all trials
      probably reflects the inclusion of patients with incompletely resected tumors,
      whose prognosis is similar to the prognosis of patients with locally advanced who
      do not undergo resection, making these trials difficult to interpret. More
      precise clinical staging and selection of patients appropriate for surgical
      resection is an important goal. The keys to the successful integration of
      radiotherapy in the care of patients with localized pancreatic cancer are
      selection, sequencing and smaller treatment volumes. A strategy of initial
      chemotherapy followed by consolidation with a well-tolerated chemoradiation
      regimen both in the adjuvant and locally advanced settings maximizes benefits of
      both treatment options, which are in fact complementary. Herein, we discuss the
      rationale for this approach as well as the ongoing investigation of novel
      radiation approaches designed to enhance outcome through the molecular and
      physical targeting of disease as well as the investigation of neoadjuvant
      chemoradiation in radiographically resectable and borderline resectable
      pancreatic cancer.

PMID- 19167923
TI  - Clinical and molecular characteristics of hepatitis A virus infections during the
      years 1992-2003 in Ogaki, a centrally located city of Japan.
AB  - BACKGROUND: The emergence of imported hepatitis A virus (HAV) strains from other
      regions is a feature of acute hepatitis A in developed countries as well as the
      decrease in number of cases. OBJECTIVES: Between 1992 and 2003 we investigated
      the clinical and molecular characteristics of acute HAV infections experienced at
      a single institution located in a middle city of Japan. STUDY DESIGN: A total of
      172 patients were admitted to our institution between 1992 and 2003 with the
      diagnosis of acute hepatitis A. Clinical features of hepatitis and molecular
      epidemiology were analyzed. RESULTS: The number of patients with acute hepatitis
      A markedly decreased during the study period. Phylogenetic analysis showed that
      all analyzed HAV strains belonged to HAV genotype IA. HAV strains clustered into
      four groups and strains of patients belonging to a cluster presented with HAV
      infection with an interval of more than 4 years. CONCLUSIONS: Several identical
      or closely related HAV strains with high homology continue to circulate in Ogaki,
      Japan, during a 12-year period, causing sporadic cases of acute hepatitis A
      infection with strains of genotype IA HAV.

PMID- 19167922
TI  - Nickel(II) and copper(II) complexes with Schiff base ligand 2,6-diacetylpyridine
      bis(carbohydrazone): synthesis and IR, mass, (1)H NMR, electronic and EPR
      spectral studies.
AB  - Nickel(II) and copper(II) complexes with general formula [M(H(3)DAPC)X] and
      [M(H(2)DAPC)H(2)O], where M=Ni(II) and Cu(II), X=NO(3)(-), Cl(-) and CH(3)COO(-),
      and DAPC=2,6-diacetylpyridine-bis(carbohydrazone), have been synthesized and
      structurally characterized by elemental analyses, molar conductance measurements,
      magnetic susceptibility measurements and spectral techniques like IR, UV and EPR.
      The nickel(II) and copper(II) complexes are octahedral and tetragonal
      coordination geometries, respectively. The EPR spectra of copper complexes in
      powdered form show a broad signal with g values in order g(||)>g(
      perpendicular)>2.0023. The value of covalency factor beta and orbital reduction
      factor k accounts for the covalent nature of the complexes.

PMID- 19167924
TI  - Prognostic interactions between statins and in-hospital revascularisation on the
      outcome of acute coronary syndrome.
AB  - AIM: To examine if the prognostic benefit of in-hospital revascularisation on
      survival among patients with acute coronary syndrome (ACS) was influenced by the
      use of statins at the initial hospital discharge. METHODS: All ACS survivors
      discharged from Dunedin and Invercargill coronary care units between the years
      2000 and 2002 were included. RESULTS: Of the 1057 hospital survivors with ACS
      (age 64.9+/-12.6 years, 63% male), 481 (45.5%) had in-hospital revascularisation
      (CABG in 123 patients and PCI in 377, including 19 with both procedures). Statins
      were prescribed at discharge in 47% of patients without and 73% of patients with
      revascularisation. Revascularisation was associated with lower mortality up to 5
      years of follow-up (hazard ratio 0.29, 95% confidence interval 0.20-0.42). After
      adjusting for baseline differences and the use of statins, the hazard ratio was
      0.39 (95% confidence interval 0.27-0.58). While the use of statins was a
      predictor for long-term survival (p<0.001), no significant interaction was found
      between the use of statins and in-hospital revascularisation in predicting
      survival. CONCLUSION: Both in-hospital revascularisation and the use of statins
      at hospital discharge independently improved outcome over a follow-up period of 2
      5 years. There was no prognostic interaction detected between these two
      beneficial therapies.

PMID- 19167926
TI  - The therapeutic helminth?
AB  - By definition, parasites harm their hosts. Yet substantial evidence from animal
      models of human disease support the hypothesis that infection with helminths can
      suppress the development of other maladies. Here, the view is presented that
      assessment of the immunophysiological response to helminths could identify that
      infection with specific parasites would be therapeutically useful (although many
      helminths could not fulfil this role) and lead to precise knowledge of the immune
      events following infection, to identify ways to intervene in disease processes
      (in the absence of infection per se) that can be used to treat, and eventually
      cure, inflammatory and autoimmune disease.

PMID- 19167927
TI  - The merozoite has landed: reticulocyte-binding-like ligands and the specificity
      of erythrocyte recognition.
AB  - Plasmodium falciparum erythrocyte invasion depends on several imperfectly
      understood multiprotein families. Two recent papers have shifted our
      understanding of the P. falciparum reticulocyte-binding-like family to the level
      of individual amino acids by identifying an erythrocyte-binding domain in one
      ligand and showing that polymorphisms in another can change the species
      specificity of erythrocyte binding. Erythrocyte invasion might be even more
      complex and harder to target than previously thought.

PMID- 19167928
TI  - Importance of membrane materials for blood purification devices in critical care.
AB  - Choosing dialyzers is more important in blood purification in critical care
      because therapeutic conditions (especially the amount of dialysate) are usually
      limited. Then, adsorption is the third major mechanism of removing toxic
      substances from patients in these treatments. Several commercial dialyzers
      designed for acute blood purification therapy were investigated by performing
      aqueous ultrafiltration experiments to demonstrate the importance of the membrane
      materials. Polymethylmethacrylate (PMMA) showed strong adsorptive characteristics
      to alpha-chymotripsinogen A (MW 25,000) but showed much less adsorptive
      characteristics to cytochrome C (MW 12,400). On the contrary, polyacrylonitrile
      (PAN) showed relatively lower affinity and polysulfone (PS) showed essentially no
      affinity to these proteins. Time and concentration dependent characteristics of
      clearance for these solutes were also demonstrated in PMMA. These facts were also
      verified in other dialyzers with another PMMA and polyester polymer alloy (PEPA)
      designed for chronic hemodialysis, which concluded that adsorption found in PMMA
      may be due to the occlusion of protein molecules into pores of the membrane.
      Choosing membrane materials is, therefore, important not only in removing
      inflammatory cytokines but also considering the loss of albumin in acute and
      chronic treatments.

PMID- 19167929
TI  - Familial aggregation of IgAD and autoimmunity.
AB  - BACKGROUND: The prevalence of autoimmunity is thought to be increased among IgA
      deficient (IgAD) individuals. However, it is currently unclear if the two
      conditions coincide within families. OBJECTIVE: To evaluate the prevalence of
      autoimmunity among IgAD individuals and their 1 degrees relatives. MATERIAL AND
      METHODS: A total of 43 IgAD individuals (32 adults and 11 children) and all
      available 1 degrees relatives were evaluated by a physician. A family history of
      autoimmunity was obtained, together with physical examination and a structured
      questionnaire that focused on symptoms and signs suggestive of autoimmunity.
      RESULTS: Eight of the 32 (25%) adult IgAD, were found to have definite
      autoimmunity, with organ specific- and systemic autoimmune diseases equally
      distributed. None of the IgAD children had autoimmunity. Among the 1 degrees
      relatives, 27/269 (10%) had autoimmunity, compared to an estimate of 5% in the
      general population (p<0.05). CONCLUSION: Autoimmune diseases are highly prevalent
      in individuals with IgAD and more common in their 1 degrees relatives than
      expected, thus, suggesting a possible common genetic component.

PMID- 19167930
TI  - Gastric metastasis of Merkel cell carcinoma.

PMID- 19167931
TI  - Selective activation of the sympathetic ganglia by centrally administered
      corticotropin-releasing factor in rats.
AB  - The sympathetic efferent pathway projects to the sympathetic ganglia and the
      adrenal medulla. In this study, we examined centrally administered corticotropin
      releasing factor (CRF)-induced neuronal activation of noradrenergic
      postganglionic neurons in several kinds of the sympathetic ganglia (superior
      cervical, stellate and celiac ganglia) in anesthetized rats. CRF significantly
      increased c-Fos expression in the celiac and stellate ganglia, with more
      pronounced effect on the celiac ganglion. On the other hand, CRF had no effect on
      c-Fos expression in the superior cervical ganglion even at a higher dose. These
      results suggest that brain CRF selectively regulates neuronal activity of each
      sympathetic ganglion.

PMID- 19167933
TI  - Large villous adenoma of the appendix: a case treated with sequential endoscopic
      minimal surgical technique.

PMID- 19167925
TI  - Safety and efficacy of tibolone in breast-cancer patients with vasomotor
      symptoms: a double-blind, randomised, non-inferiority trial.
AB  - BACKGROUND: Vasomotor symptoms and bone loss are complications frequently induced
      by adjuvant treatment for breast cancer. Tibolone prevents both side-effects, but
      its effect on cancer recurrence is unknown. The aim of this study was to show non
      inferiority of tibolone to placebo regarding risk of recurrence in breast-cancer
      patients with climacteric complaints. METHODS: Between July 11, 2002, and Dec 20,
      2004, women surgically treated for a histologically confirmed breast cancer (T(1
      3)N(0-2)M(0)) with vasomotor symptoms were randomly assigned to either tibolone
      2.5 mg daily or placebo at 245 centres in 31 countries. Randomisation was done by
      use of a centralised interactive voice response system, stratified by centre,
      with a block size of four. The primary endpoint was breast-cancer recurrence,
      including contralateral breast cancer, and was analysed in the intention-to-treat
      (ITT) and per-protocol populations; the margin for non-inferiority was set as a
      hazard ratio of 1.278. This study is registered with ClinicalTrials.gov, number
      NCT00408863. FINDINGS: Of the 3148 women randomised, 3098 were included in the
      ITT analysis (1556 in the tibolone group and 1542 in the placebo group). Mean age
      at randomisation was 52.7 years (SD 7.3) and mean time since surgery was 2.1
      years (SD 1.3). 1792 of 3098 (58%) women were node positive and 2185 of 3098
      (71%) were oestrogen-receptor positive. At study entry, 2068 of 3098 (67%) women
      used tamoxifen and 202 of 3098 (6.5%) women used aromatase inhibitors. The mean
      daily number of hot flushes was 6.4 (SD 5.1). After a median follow-up of 3.1
      years (range 0.01-4.99), 237 of 1556 (15.2%) women on tibolone had a cancer
      recurrence, compared with 165 of 1542 (10.7%) on placebo (HR 1.40 [95% CI 1.14
      1.70]; p=0.001). Results in the per-protocol population were similar (209 of 1254
      [16.7%] women in the tibolone group had a recurrence vs 138 of 1213 [11.4%] women
      in the placebo group; HR 1.44 [95% CI 1.16-1.79]; p=0.0009). Tibolone was not
      different from placebo with regard to other safety outcomes, such as mortality
      (72 patients vs 63 patients, respectively), cardiovascular events (14 vs 10,
      respectively), or gynaecological cancers (10 vs 10, respectively). Vasomotor
      symptoms and bone-mineral density improved significantly with tibolone, compared
      with placebo. INTERPRETATION: Tibolone increases the risk of recurrence in breast
      cancer patients, while relieving vasomotor symptoms and preventing bone loss.
      FUNDING: Schering-Plough (formerly NV Organon, Oss, Netherlands).

PMID- 19167932
TI  - Population-specific variation in haplotype composition and heterozygosity at the
      POLB locus.
AB  - DNA polymerase beta plays a central role in base excision repair (BER), which
      removes large numbers of endogenous DNA lesions from each cell on a daily basis.
      Little is currently known about germline polymorphisms within the POLB locus,
      making it difficult to study the association of variants at this locus with human
      diseases such as cancer. Yet, approximately thirty percent of human tumor types
      show variants of DNA polymerase beta. We have assessed the global frequency
      distributions of coding and common non-coding SNPs in and flanking the POLB gene
      for a total of 14 sites typed in approximately 2400 individuals from
      anthropologically defined human populations worldwide. We have found a marked
      difference between haplotype frequencies in African populations and in non
      African populations.

PMID- 19167934
TI  - Endoscopic submucosal dissection: learning from the Japanese experience.

PMID- 19167935
TI  - Self-assembling biomaterials.

PMID- 19167936
TI  - Psychological aspects in day-case surgery.
AB  - Many reasons have helped to achieve the expansion of day surgery in health care
      system. First, surgical and pharmacological advances have dramatically reduced
      length of hospitalizazion needed for recovery from anaesthesia and operation.
      Second, day surgery has the potential to be more cost-effective than inpatient
      surgery. Third, patients generally are satisfied with day surgery because they
      have no or minimal side effects, are discharged the same day they have surgery
      and there is a minimal disruption in their everyday life. In this new era of
      safe, efficient, convenient, economical and speedy surgical interventions and
      minimal hospital stay, considerable attention must be given to some psychological
      issues, as anxiety and its management and information provision. Several studies
      have highlighted causes and degree of anxiety experienced by patients admitted in
      day surgery and a lack of an adequate and documented support. A combination of
      consistent strategies and interpersonal skills may have the potential to become
      the base of a formal psychoeducational plan implemented to manage anxiety. An
      essential component of anxiety management is information provision. Since lack or
      inadequacy of information is one of the main complaints with day surgery and the
      most common cause of patients' dissatisfaction, a formal and structured programme
      of information delivery is required. The timely and appropriate provision of
      different levels of information tailored to patient's coping styles and
      preferences has been strongly recommended. The information provided must cover
      the whole range of procedural, behavioural and sensory information and include
      pre-operative, operative and post-operative phases.

PMID- 19167937
TI  - Neuroendocrine carcinomas of the breast.
AB  - INTRODUCTION: Neuroendocrine (NE) breast cancers encompass a heterogeneous group
      of tumours showing morphological features similar to those of NE neoplasms of the
      gut and lung and expressing one or more neuroendocrine markers (neuron specific
      enolase, chromogranins synaptophysin) in at least 50% of tumour cells. They are
      rare lesions representing about 2-3% of all breast cancers and affecting more
      frequently elderly patients. AIM: Prospective observational study is to analyse
      the clinico-pathological aspects of NE carcinomas of the breast undergone
      surgical resection compared to breast carcinomas with a minor neuroendocrine
      component and to conventional invasive ductal or lobular cancers. MATERIAL AND
      METHOD: Thirty-five consecutive breast carcinomas showing morphological features
      suggestive of an endocrine differentiation were selected among breast cancers
      undergone surgical treatment during the period of January 1979-December 2004.
      RESULTS: The 35 patients were divided into two categories: 13 neuroendocrine
      carcinomas (NECs) and 22 ductal carcinomas with a minor neuroendocrine component
      (DC-NE). The average follow-up was 60 months. The patients with CNE developed
      breast cancer in an advanced age compared to the patients with infiltrating
      ductal carcinoma NAS or infiltrating lobular carcinoma. We did not find recurrent
      disease in the NEC group, while it was observed in 2 patients (9%) with DC-NE, in
      6 cases (17%) with infiltrating ductal carcinoma NAS and in 7 cases (20%) with
      infiltrating lobular carcinoma. DISCUSSION: The CNE compared with the
      infiltrating ductal and lobular carcinoma are statistically different in relation
      to the expression of the receptor of c-erb-B2, p53, progesterone, for the lymph
      node state at diagnosis and the risk of reappearance of breast tumour. Our study
      confirms the choice to consider the neuroendocrine carcinoma of the breast as a
      separate histological group and seems to suggest a less aggressiveness of this
      type of tumour.

PMID- 19167938
TI  - Laparoscopic cholecystectomy as day-surgery procedure: current indications and
      patients' selection.
AB  - AIM OF THE STUDY: To review the current indications, to establish predictive
      factors of success and the safety of LC as a day-surgery procedure. METHODS:
      Randomized clinical trials were searched on PubMed between January 2000 and June
      2008 using "laparoscopic cholecystectomy", "day-surgery" as keywords. RESULTS: A
      total of 20 trials was identified and analyzed. The indications for LC in day
      surgery unit were symptomatic and chronic cholelitiasis without evidence of
      common bile duct stones; acute cholecystitis and pancreatitis cases were
      excluded. The trials considered as inclusion criteria: ASA score, BMI, social
      aspect and the preoperative workout included: abdominal US, liver function tests
      and routine preoperative tests, while the results considered the reasons for
      hospital stays and for readmission and measured patient satisfaction; some trials
      included analyze of costs of LC as day-surgery procedure the role of the
      surgeon's experience. DISCUSSION: The present study confirms that day-surgery LC
      is safe and feasibility in selected patients; serious complications are rare and
      most frequently prolonged hospital stay and the readmission are connected with
      minor and more easily controlled complications or social reasons. Outpatient
      surgery requires careful planning and preparation in order to reach acceptable
      patients' satisfaction: preoperative workout is extremely imports allowing to
      reduce errors selection. Considering surgical training, it has been demonstrated
      that in the centres in which the trainees are involved in day-surgery LC there
      not significant difference in terms of number of complications, patient outcomes,
      prolonged stay and readmission. The adequate control of pain, nausea or vomiting
      is essential component in day-case LC service and it is possible at home after
      LC. CONCLUSION: Day-case laparoscopic cholecystectomy is feasible with an
      acceptable discharge rate and level of patient satisfaction. The success depends
      on appropriate patient selection and on well-trained staff and skilful operative
      technique together with safe anaesthesia.

PMID- 19167939
TI  - Video-assisted thyroidectomy performed in a one-day surgery setting.
AB  - BACKGROUND AND AIM: Evidence base data have demonstrated that video-assisted
      thyroidectomy (VAT) has good results regarding safety, morbidity, patient cure
      rate, pain and cosmesis. Aim of this study was to evaluate the performance of VAT
      in an ambulatory setting (i.e. one-day surgery, <24-h stay). MATERIALS AND
      METHODS: Between September 2007 and July 2008, 43 patients underwent VAT in a one
      day surgery division. Patient selection criteria for VAT were: thyroid nodules
      <30 mm, gland volume <20 ml, no history of thyroiditis or neck surgery or
      irradiation, "low risk" papillary carcinoma and absence of enlarged lymph nodes.
      One-day surgery patient selection criteria were medical and social logistic
      (Materazzi G, et al. Eur Surg Res 2007;39:182-8). Intraoperative neuromonitoring
      (IONM) was used for RLN identification. Intact parathyroid hormone (iPTH) levels
      were determined early postoperatively at +6-h. Postoperative complications,
      conversion rate were analyzed. RESULTS: No cases required conversion to open
      surgery or ordinary recovery (i.e. >24h). Incidence of temporary
      hypoparathyroidism was 11.6% (5/43) with no case of symptomatic hypocalcemia.
      Incidence of temporary RLN injury was 2.3% (1 patient) with no case of permanent
      or bilateral RLN injury. All patients were satisfied with the type of recovery.
      CONCLUSIONS: This preliminary report is an example of the safe incorporation
      between new technologies (IONM, early iPTH measurement) with improvement of the
      quality and safety of VAT performed in a one-day surgery setting.

PMID- 19167940
TI  - The fetus of a diabetic mother: sonographic evaluation.
AB  - Maternal hyperglycemia is responsible for many fetal adverse outcomes. Ultrasound
      examination of these pregnancies aims at an early detection of congenital
      malformations, assessment of fetal well-being, and fetal growth. This evaluation
      will influence clinical decision in determining the best time and mode of
      delivery. We reviewed data from the literature on accuracy, usefulness, and
      indications of ultrasound examinations in pregnancies complicated with diabetes
      mellitus, whether pregestational or gestational.

PMID- 19167941
TI  - Does the trichophytic technique have any role in facial wound closure? A
      hypothesis.

PMID- 19167942
TI  - A new trend for the treatment of blepharoptosis: frontalis-orbicularis oculi
      muscle flap shortening technique.
AB  - Operation techniques for blepharoptosis have been a great challenge for plastic
      surgeons. Complications and recurrence in conventional operations of eyelid
      ptosis cannot be neglected. The finding of the close linkage between the
      longitudinal-oriented frontalis muscle (FM) and the horizontal-orientated
      orbicularis oculi (OOM) muscle convinced us of the efficacy to develop the
      dynamic and powerful Frontalis-Orbicularis Oculi Muscle (FOOM) flap-shortening
      technique which corrects blepharoptosis with good biomechanics in place of the
      traditional frontalis muscle sling. From January 2003 to September 2007, the FOOM
      flap shortening technique was applied on 35 ptotic eyelids of 31 patients, age
      ranging from 18 year to 77 years. All FOOM flaps were harvested and adjusted
      depending on the severity of the blepharoptosis. The follow up period ranged from
      5 to 55 months. Thirty eyelids had good results, with the degree of ptosis less
      than 2mm. There were only five recurrent ptotic eyelids due to technical
      undercorrection. The estimation of resected length is measured when the FOOM flap
      is fully stretched and the length is approximately 22.0-23.0 mm for mild cases,
      23.0-24.0 mm for moderate cases, and 25.0-26.0 mm for severe blepharoptosis. The
      FOOM flap-shortening technique was developed and corrected blepharoptosis with
      good results compared to conventional operation techniques. It achieves
      antagonistic equilibrium with ideal biomechanics by debilitating eye-closing
      power and enhancing eye-opening power.

PMID- 19167943
TI  - Metabolic syndrome in children: prevention potential.

PMID- 19167944
TI  - Accountability for lifelong learning.

PMID- 19167945
TI  - Reducing foodservice waste: going green can save green.

PMID- 19167946
TI  - Networking moves online.

PMID- 19167947
TI  - Aiding the public policy process with member knowledge.

PMID- 19167948
TI  - The influence of maternal acculturation on child body mass index at age 24
      months.
AB  - OBJECTIVE: Obesity rates in preschool-aged children are greatest among Latinos.
      Studies of the relationship of acculturation to obesity among Latino immigrants
      have primarily focused on adults and adolescents. We examined the influence of
      maternal acculturation on child body mass index (BMI) at age 24 and 36 months
      among predominantly Latino, low-income mother-child pairs enrolled in the Special
      Supplemental Nutrition Program for Women, Infants, and Children. DESIGN AND
      METHODS: Maternal characteristics were obtained from interviewer-administered
      surveys conducted in English or Spanish at 6 to 20 weeks postpartum among 679
      participants in a randomized controlled trial of a health promotion intervention
      in two urban areas in the Northeast. Acculturation measures included: nativity
      (born in the United States vs foreign born), parents' nativity, years of US
      residence (<8 years vs > or =8 years), and exclusive use of native language vs
      nonexclusive use (mixed or English only). Following repeated mailings and
      telephone calls requesting permission to obtain their child's height and weight
      from Special Supplemental Nutrition Program for Women, Infants, and Children
      records, informed consent was obtained from 108 mothers. Multivariable linear
      regression models of maternal acculturation and child BMI z score at age 24
      months and age 36 months were estimated among all mother-child pairs and within
      immigrant-only mother-child pairs, adjusting for relevant maternal
      characteristics. RESULTS: At age 24 months, children of mothers with exclusive
      use of native language had higher BMI z scores compared to children of mothers
      with nonexclusive use among 91 mother-child pairs (beta=.74, P=0.02) and within
      63 immigrant-only mother-child pairs (beta=.92, P=0.009). CONCLUSIONS: Exclusive
      use of native language was associated with greater BMI in children as young as
      age 24 months. Future research should examine the mechanisms by which mothers'
      language acculturation may affect proximal determinants of energy balance in
      preschool children, including breastfeeding practices, dietary intake, and
      physical activity.

PMID- 19167949
TI  - US adolescents and MyPyramid: associations between fast-food consumption and
      lower likelihood of meeting recommendations.
AB  - OBJECTIVE: To determine whether fast-food consumption is associated with
      adolescents' food group intakes and likelihood of meeting recommendations
      outlined in the MyPyramid Food Guidance System. DESIGN: Data from two 24-hour
      recalls collected in What We Eat in America, National Health and Nutrition
      Examination Survey 2003-2004 were analyzed. Fast-food consumers were divided into
      tertiles based on the proportion of 2-day energy intake derived from fast food.
      SUBJECTS: Adolescent boys and nonpregnant girls aged 12 to 19 years (n=1,956).
      STATISTICAL ANALYSES PERFORMED: All statistical analyses included sample weights
      to account for the survey design. Regression analyses were used to detect
      associations between fast-food consumption and both food group intakes and
      percentages of individuals meeting MyPyramid recommendations, and to predict odds
      of meeting recommendations by fast-food consumption level. RESULTS: Fast-food
      consumption was associated negatively with MyPyramid fruit and milk group intakes
      (boys and girls) and positively with discretionary energy and solid fats (girls
      only). Negative associations were also found between fast-food consumption and
      percentages of adolescents meeting recommendations for milk (boys), fruits
      (girls), and vegetables and discretionary energy (boys and girls). Compared with
      those consuming no fast food, adolescents in the highest tertile of energy from
      fast food were less likely to meet recommendations for vegetables (odds ratio
      [OR]=0.16, 95% confidence interval [CI]: 0.05 to 0.52 for boys; OR=0.18, 95% CI:
      0.04 to 0.79 for girls) and discretionary energy (OR=0.41, 95% CI: 0.22 to 0.77
      for boys; OR=0.04, 95% CI: 0.01 to 0.24 for girls). No relationships were found
      between fast-food consumption and grains, meat/beans, and oils. CONCLUSIONS:
      Adolescents' intakes, whether containing fast food or not, need improvement. Fast
      food is one factor that impacts adolescents' intake of MyPyramid groups and their
      likelihood of meeting recommendations. Awareness of fast-food's role in
      discrepancies between adolescent intakes and MyPyramid recommendations can aid
      professionals in designing effective strategies to improve adolescents' diets.

PMID- 19167950
TI  - Differential influence of diet and physical activity on components of metabolic
      syndrome in a multiethnic sample of children.
AB  - BACKGROUND: Treatment of the metabolic syndrome in adults is generally approached
      with diet and physical activity. The influence of diet and physical activity on
      cardiometabolic outcomes in children has not been clearly established. OBJECTIVE:
      The main objective of this study was to test the hypothesis that the distribution
      of energy from fat and carbohydrate in addition to limited time spent engaging in
      physical activity would contribute to the prevalence of the metabolic syndrome
      and its components in a multiethnic pediatric population. DESIGN: Observational,
      cross-sectional study. Diet was assessed by two 24-hour recalls, physical
      activity by accelerometry, body composition by dual-energy absorptiometry, and
      glucose and lipid levels using fasting sera. MAIN OUTCOME MEASURES: Presence of
      metabolic syndrome and its components. SUBJECTS: 202 African-American (n=79),
      white (n=68), or Hispanic (n=55) healthy children aged 7 to 12 years. STATISTICAL
      ANALYSIS: The contribution of diet and physical activity to the metabolic
      syndrome and its components were assessed by logistic regression and multiple
      linear regression analyses. RESULTS: Prevalence of the metabolic syndrome in the
      total sample was 8.4%, with Hispanics more likely than whites and African
      Americans to meet the criteria. A greater intake of energy from carbohydrate was
      related to a greater waist circumference and higher concentrations of
      triglyceride and glucose particularly apparent within the African-American sample
      (P<0.05). Fat intake was associated with a lower waist circumference (P<0.05) and
      with lower concentrations of triglyceride (P<0.05) and glucose (P<0.001) in the
      total sample. Greater moderate/hard physical activity was associated with higher
      high-density lipoprotein cholesterol concentrations in whites (P<0.05). Increased
      sedentary behavior was related to greater glucose concentration in whites and
      Hispanics (P<0.05 for both). CONCLUSIONS: Diet composition was more closely
      related to the components of the metabolic syndrome than was physical activity,
      with carbohydrate intake being adversely related to waist circumference,
      triglyceride levels, and glucose levels. Furthermore, relationships among diet
      and metabolic syndrome outcomes were stronger among African-American children,
      suggesting that nutrition interventions in this group may be particularly
      beneficial.

PMID- 19167951
TI  - Urinary isoflavones and their metabolites validate the dietary isoflavone intakes
      in US adults.
AB  - BACKGROUND: Isoflavones are derived from dietary sources and considered to
      promote health by preventing the onset of such chronic diseases as cardiovascular
      disease, cancer, and osteoporosis. Valid and reliable estimation of isoflavone
      intake is a prerequisite to establishing biological functions of isoflavones on
      health risks. OBJECTIVE: This study aimed to validate the approach of estimating
      dietary isoflavone intake with respective urinary isoflavone concentrations in US
      adults. DESIGN: Data from the US Department of Agriculture isoflavone database
      and dietary recalls of 2,908 US adults with urinary isoflavone data in the 1999
      2002 National Health and Nutrition Examination Survey were used. RESULTS: Dietary
      isoflavone was consumed by only 35% of adults in a day with an average intake of
      3.1 mg/day, which resulted in a mean intake of 1.0 mg/day for all US adults. The
      isoflavone intakes were from genistein (55%), diadzein (35%), glycitein (7%),
      biochanin A (2%), and formononetin (2%). Both daily total and energy adjusted
      isoflavone intake differed by race/ethnicity subgroups (P<0.05) and was
      associated positively with income (P<0.01) and inversely with body mass index
      (P<0.05). Geometric mean urinary isoflavone concentration was 5.0 ng/mL among
      isoflavone consumers and the urinary genistein and daidzein excretion correlated
      with their isoflavone intake levels (P<0.01). CONCLUSIONS: In large population
      based studies, estimated dietary isoflavone intake can be validated by urinary
      isoflavones. Further studies are needed at an individual level to validate
      dietary isoflavone intake by urinary isoflavone concentration.

PMID- 19167952
TI  - Cluster analysis defines distinct dietary patterns for African-American men and
      women.
AB  - BACKGROUND: African Americans have a higher prevalence of diet-related chronic
      diseases than the general US population. Recent evidence suggests that examining
      dietary patterns rather than specific nutrients may better allow public health
      professionals to translate national dietary goals into practical dietary
      recommendations that are culturally relevant and sex-specific. OBJECTIVE: To
      examine and characterize the dietary patterns of African-American men and women
      using cluster analysis. DESIGN: Participants older than the age of 18 years were
      recruited from a variety of locations and completed a self-administered
      questionnaire. SUBJECTS/SETTING: Seven-hundred sixty-three African-American men
      and women in North Central Florida. STATISTICAL ANALYSES PERFORMED: Cluster
      analysis was done with the VARCLUS procedure and Ward's clustering approach in
      the Statistical Analysis System program. The pseudo-t(2) statistic was then used
      to identify the optimal numbers of clusters of men and women with distinctive
      food-consumption patterns. RESULTS: Cluster analyses identified six clusters of
      men with 13 distinctive dietary patterns and six clusters of women with 15
      distinctive dietary patterns. Pairwise comparisons of group means indicated
      notable differences in intakes between clusters of women in all but two food
      clusters. Pairwise comparisons of group means indicated notable differences in
      intakes between clusters of men in all but two food clusters. CONCLUSIONS: The
      study illustrated that cluster analysis can be used to identify groups of African
      Americans with unique patterns of food consumption. They also suggest that a
      single "typical" eating pattern does not exist for African Americans and that
      dietary pattern vary by sex.

PMID- 19167953
TI  - A low-fat vegan diet elicits greater macronutrient changes, but is comparable in
      adherence and acceptability, compared with a more conventional diabetes diet
      among individuals with type 2 diabetes.
AB  - BACKGROUND: Although therapeutic diets are critical to diabetes management, their
      acceptability to patients is largely unstudied. OBJECTIVE: To quantify adherence
      and acceptability for two types of diets for diabetes. DESIGN: Controlled trial
      conducted between 2004 and 2006. SUBJECTS/SETTING: Individuals with type 2
      diabetes (n=99) at a community-based research facility. Participants were
      randomly assigned to a diet following 2003 American Diabetes Association
      guidelines or a low-fat, vegan diet for 74 weeks. MAIN OUTCOME MEASURES:
      Attrition, adherence, dietary behavior, diet acceptability, and cravings.
      STATISTICAL ANALYSES: For nutrient intake and questionnaire scores, t tests
      determined between-group differences. For diet-acceptability measures, the
      related samples Wilcoxon sum rank test assessed within-group changes; the
      independent samples Mann-Whitney U test compared the diet groups. Changes in
      reported symptoms among the groups was compared using chi(2) for independent
      samples. RESULTS: All participants completed the initial 22 weeks; 90% (45/50) of
      American Diabetes Association guidelines diet group and 86% (42/49) of the vegan
      diet group participants completed 74 weeks. Fat and cholesterol intake fell more
      and carbohydrate and fiber intake increased more in the vegan group. At 22 weeks,
      group-specific diet adherence criteria were met by 44% (22/50) of members of the
      American Diabetes Association diet group and 67% (33/49) of vegan-group
      participants (P=0.019); the American Diabetes Association guidelines diet group
      reported a greater increase in dietary restraint; this difference was not
      significant at 74 weeks. Both groups reported reduced hunger and reduced
      disinhibition. Questionnaire responses rated both diets as satisfactory, with no
      significant differences between groups, except for ease of preparation, for which
      the 22-week ratings marginally favored the American Diabetes Association
      guideline group. Cravings for fatty foods diminished more in the vegan group at
      22 weeks, with no significant difference at 74 weeks. CONCLUSIONS: Despite its
      greater influence on macronutrient intake, a low-fat, vegan diet has an
      acceptability similar to that of a more conventional diabetes diet. Acceptability
      appears to be no barrier to its use in medical nutrition therapy.

PMID- 19167954
TI  - Impact of garden-based youth nutrition intervention programs: a review.
AB  - Garden-based nutrition-education programs for youth are gaining in popularity and
      are viewed by many as a promising strategy for increasing preferences and
      improving dietary intake of fruits and vegetables. This review examines the
      scientific literature on garden-based youth nutrition intervention programs and
      the impact on nutrition-related outcomes. Studies published between 1990 and 2007
      were identified through a library search of databases and an examination of
      reference lists of relevant publications. Studies were included if they involved
      children and adolescents in the United States and examined the impact of garden
      based nutrition education on fruit and/or vegetable intake, willingness to taste
      fruits and vegetables, preferences for fruits and vegetables, or other nutrition
      related outcomes. Only articles published in peer-reviewed journals in English
      were included in the review. Eleven studies were reviewed. Five studies took
      place on school grounds and were integrated into the school curriculum, three
      studies were conducted as part of an afterschool program, and three studies were
      conducted within the community. Studies included youth ranging in age from 5 to
      15 years. Findings from this review suggest that garden-based nutrition
      intervention programs may have the potential to promote increased fruit and
      vegetable intake among youth and increased willingness to taste fruits and
      vegetables among younger children; however, empirical evidence in this area is
      relatively scant. Therefore, there is a need for well-designed, evidenced-based,
      peer-reviewed studies to determine program effectiveness and impact. Suggestions
      for future research directions, including intervention planning, study design,
      evaluation, and sustainability are provided.

PMID- 19167955
TI  - Improving literacy about energy-related issues: the need for a better
      understanding of the concepts behind energy intake and expenditure among
      adolescents and their parents.
AB  - Despite the need for effective obesity prevention strategies, little research has
      assessed adolescents' knowledge about basic concepts of energy intake,
      expenditure, and balance. Using data from 349 adolescent-caregiver pairs
      (recruited from Minneapolis/St Paul, MN metro region, 2006-2007), cross-sectional
      linear regression was used to assess adolescent and parental knowledge related to
      energy intake and expenditure as a predictor of adolescent weight-related
      behaviors and outcomes. Findings indicated that knowledge related to energy
      intake and expenditure was highly variable, with a substantial proportion of
      participants (particularly adolescents) lacking knowledge on a range of concepts.
      Adolescent knowledge was positively associated with moderate physical activity
      and negatively associated with television viewing (P<0.05), but it was not
      associated with sweetened beverage consumption, fast food intake, weight status,
      and/or body composition. Although overall parental knowledge was a significant
      predictor of adolescent knowledge (P<0.01), parent-child agreement on individual
      items was poor. As adolescents age, low literacy in this area may set the stage
      for poor decision-making related to energy balance and healthy weight
      maintenance. However, in that knowledge was not a significant predictor of
      various weight-related outcomes, these and other findings suggest that purely
      education-based health promotion strategies are insufficient to initiate long
      term healthful behavior change. Educational strategies may be effective when
      combined with those also targeting familial, social, and environmental
      influences. The examination of interactive effects between individual-level and
      environmental influences on health behavior is an important area for future
      obesity-related research.

PMID- 19167956
TI  - Americans' awareness, knowledge, and behaviors regarding fats: 2006-2007.
AB  - In recent years, epidemiologic and clinical studies, public and regulatory policy
      activity, and media coverage have focused on issues related to trans fats. To
      help increase awareness and understanding of trans fats and other fats, the
      American Heart Association (AHA) launched the "Face the Fats" national consumer
      education campaign in April 2007. The AHA commissioned a quantitative tracking
      survey between 2006 and 2007 to measure changes in consumer awareness, knowledge,
      and behaviors related fats and oils and their perceived impact on heart disease.
      The survey was conducted by Cogent Research. Data were collected during March
      2006 and May 2007. At both time points, the survey included a representative
      sample of the American population age 18 to 65 years (n=1,000). The sampling plan
      for the survey was designed based on the 2000 and 2003 US Census. The margin of
      error was +/-3.10 percentage points. Awareness of trans fats increased during the
      1-year study period. In 2007, 92% of respondents were aware of trans fats, an
      increase from 84% in 2006 (P<0.05). The 2007 level was similar to the awareness
      of saturated fats (93%). Perceptions that certain fats and oils heighten the risk
      of heart disease increased for trans fats (73% in 2007 vs 63% in 2006; P<0.05),
      saturated fats (77% in 2007 vs 73% in 2006; P<0.05), and partially hydrogenated
      oils (56% in 2007 vs 49% in 2006; P<0.05). Knowledge about food sources of
      different fats remained low. On an unaided basis, 21% could name three food
      sources of trans fats in 2007, up from 17% in 2006 (P<0.05). Knowledge of food
      sources of saturated fat remained unchanged at 30% in 2007. Significantly more
      respondents in 2007 reported behavioral changes related to trans fat information,
      such as buying food products because they show "zero trans fat" on labels or
      packages (37% in 2007 vs. 32% in 2006; P<0.05). Between 2006 and 2007, consumer
      awareness about trans fats increased and attained awareness levels similar to
      saturated fats. The increased awareness is associated with improved self-reported
      behaviors in grocery shopping. Nonetheless, overall knowledge, especially
      regarding food sources of saturated and trans fats, remains relatively low,
      underscoring the need for heightened consumer education activities. The positive
      change in consumer awareness about trans fats is likely attributable to the wide
      range of messages available to them, including the AHA "Face the Fats" national
      consumer education campaign.

PMID- 19167957
TI  - Excess adiposity, inflammation, and iron-deficiency in female adolescents.
AB  - Iron deficiency is more prevalent in overweight children and adolescents but the
      mechanisms that underlie this condition remain unclear. The purpose of this cross
      sectional study was to assess the relationship between iron status and excess
      adiposity, inflammation, menarche, diet, physical activity, and poverty status in
      female adolescents included in the National Health and Nutrition Examination
      Survey 2003-2004 dataset. Descriptive and simple comparative statistics (t test,
      chi(2)) were used to assess differences between normal-weight (5th < or = body
      mass index [BMI] percentile <85th) and heavier-weight girls (< or = 85th
      percentile for BMI) for demographic, biochemical, dietary, and physical activity
      variables. In addition, logistic regression analyses predicting iron deficiency
      and linear regression predicting serum iron levels were performed. Heavier-weight
      girls had an increased prevalence of iron deficiency compared to those with
      normal weight. Dietary iron, age of and time since first menarche, poverty
      status, and physical activity were similar between the two groups and were not
      independent predictors of iron deficiency or log serum iron levels. Logistic
      modeling predicting iron deficiency revealed having a BMI > or = 85th percentile
      and for each 1 mg/dL increase in C-reactive protein the odds ratio for iron
      deficiency more than doubled. The best-fit linear model to predict serum iron
      levels included both serum transferrin receptor and C-reactive protein following
      log-transformation for normalization of these variables. Findings indicate that
      heavier-weight female adolescents are at greater risk for iron deficiency and
      that inflammation stemming from excess adipose tissue contributes to this
      phenomenon. Food and nutrition professionals should consider elevated BMI as an
      additional risk factor for iron deficiency in female adolescents.

PMID- 19167958
TI  - The effect of a low-glycemic diet vs a standard diet on blood glucose levels and
      macronutrient intake in children with type 1 diabetes.
AB  - A low-glycemic index (GI) diet may lower postprandial hyperglycemia and decrease
      the risk for postabsorptive hypoglycemia in people with type 1 diabetes. However,
      insufficient evidence exists on the efficacy of a low-GI diet to support practice
      recommendations. The goal of this study was to examine the blood glucose response
      to and the macronutrient composition of low-GI meals vs usual meals consumed ad
      libitum at home in children with type 1 diabetes. A within-subject, crossover
      design was employed. Twenty-three participants were recruited between June and
      August 2006. Participants wore a continuous blood glucose monitoring system and
      completed diet diaries on 2 days. On 1 day, participants consumed their usual
      meal; on another day, participants consumed low-GI meals ad libidum. Order of the
      2 days was counterbalanced. The mean GI was 34+/-6 for the low-GI day and 57+/-6
      for the usual meal day (P<0.0001). During the low-GI day, mean daytime blood
      glucose values (125+/-28 mg/dL [6.9+/-1.5 nmol/L] vs 185+/-58 mg/dL [10.3+/-3.2
      nmol/L], P<0.001), blood glucose area above 180 mg/dL (4,486+/-6,138 vs 26,707+/
      25,038, P<0.006), and high blood glucose index (5.1+/-5.1 vs 13.6+/-7.6, P<0.001)
      were lower compared to the usual mean day. During the low-GI day, subjects
      consumed more fiber (24.5+/-12.3 g vs 14.5+/-6.1 g, P<0.007) and less fat (45.7+/
      12.2 g vs 76.8+/-32.4 g, P<0.005); however, there were no differences in energy,
      carbohydrate, or protein intake. In this pilot study, a low-GI diet was
      associated with improved diet quality and a reduction in hyperglycemia.

PMID- 19167959
TI  - Five-year longitudinal and secular shifts in adolescent beverage intake: findings
      from project EAT (Eating Among Teens)-II.
AB  - Detailed research examining concurrent longitudinal and secular changes in
      adolescent beverage intake is not currently available, particularly since the
      year 2000. This study's objective was to evaluate these trends in beverage intake
      in a large, diverse adolescent cohort. Project EAT (Eating Among Teens)-II is a 5
      year longitudinal study (n=2,516) including two cohorts, which allows for the
      observation of longitudinal changes from early to mid-adolescence (junior high to
      high school) and from mid- to late adolescence (high school to post high school).
      Project EAT-II also examined secular trends in adolescent health behavior from
      1999-2004 in mid-adolescence. Daily beverage servings were assessed using the
      Youth and Adolescent Food Frequency Questionnaire. Longitudinal findings indicate
      that intake of soda and sugar-sweetened beverages (including soda, sweetened iced
      teas, and fruit drinks) increased significantly among younger males, and alcohol
      increased across all groups (P<0.01). Consumption of certain beverages decreased
      with age: fruit juice (among all males and older females, P< or =0.02), milk
      (older adolescents, P<0.01), other milk beverages (all females and older males,
      P<0.01), diet soda (younger adolescents, P<0.01), and coffee/tea (all males and
      younger females, P<0.01). Significant secular decreases were observed in fruit
      juice and coffee/tea for males and females (P< or =0.05). Overall, these findings
      reflect recent secular and longitudinal shifts in adolescent beverage consumption
      during the critical transition period from early to mid-adolescence and mid- to
      late adolescence. Although additional research is needed to better understand
      nuances in adolescent consumption patterns, registered dietitians and other
      health care practitioners working with adolescents should address the importance
      of limiting sugar-sweetened beverages with low nutrient density.

PMID- 19167960
TI  - Genetic variants in phosphatidylethanolamine N-methyltransferase and
      methylenetetrahydrofolate dehydrogenase influence biomarkers of choline
      metabolism when folate intake is restricted.
AB  - Choline is a required nutrient with roles in liver and brain function, lipid
      metabolism, and fetal development. Recent data suggest that choline requirements
      may be altered by polymorphisms in the phosphatidylethanolamine N
      methyltransferase (PEMT) gene (ie, 5465G-->A; rs7946 and -744G-->C; rs12325817)
      and in the methylenetetrahydrofolate dehydrogenase (MTHFD1) gene (ie, 1958G-->A;
      rs2236225). This controlled feeding study, conducted in 2000-2001, examined the
      effects of the PEMT and MTHFD1 genetic variants on biomarkers of choline
      metabolism in premenopausal Mexican-American women (N=43) after a 7-week period
      of folate restriction (135 microg as dietary folate equivalents) and after a 7
      week period of folate treatment (400 and 800 microg dietary folate
      equivalents/day combined). Throughout the 14-week study choline intake remained
      constant at 349 mg/day. The genotype frequencies of the women were 3GG, 19GA, and
      21AA for PEMT G5465A; 9GG, 17GC and 17CC for PEMT G-744C; and 9GG, 21GA and 13AA
      for MTHFD1 G1958A. During folate restriction, homocysteine was adversely
      influenced by PEMT 5465AA (P=0.001 relative to the G allele) and by MTHFD1 1958AA
      (P=0.085 relative to 1958GG); whereas the decline in phosphatidylcholine was
      attenuated by PEMT -744CC (P=0.017 relative to -744GG). During folate treatment,
      no effects of the genotypes on the response of the measured variables were
      detected. These data suggest that polymorphisms in genes relevant to choline
      metabolism modulate parameters of choline status when folate intake is
      restricted. Additional studies with larger samples sizes are needed to examine
      the relationship between these genetic variants and varied choline intake in
      populations with increased demands for choline (eg, pregnant women).

PMID- 19167961
TI  - Change in food choices following a glycemic load intervention in adults with type
      2 diabetes.
AB  - The glycemic index (GI) reflects the postprandial glucose response of
      carbohydrate-containing foods, and adoption of a lower-GI diet may be beneficial
      in diabetes management. The purpose of this study was to evaluate change in food
      group intake by participants after completing an intervention that included
      instruction about carbohydrate and the GI using a quasi-experimental design.
      Recruitment occurred from February to August 2005 and September to December 2006.
      Individuals 40 to 70 years old with type 2 diabetes for 1 year or longer were
      randomly assigned to an immediate (n=55) or delayed (n=48) treatment group. A 9
      week group-based intervention regarding the quantity and type of carbohydrate for
      diabetes management was provided. Three sets of 24-hour dietary recalls were used
      to assess food-group intake. Foods were divided into nine main food groups and
      166 subgroups based on the Dietary Guidelines for Americans 2005 and the United
      States Department of Agriculture's Food Guide Pyramid. Analysis of variance was
      used to examine between-group differences and paired t test compared maintenance
      of change for the immediate group. Change in dietary GI was significantly
      different between groups upon completion of the intervention by the immediate
      group (P<0.05). Participants consumed significantly more servings of whole fruit
      and nonfat dairy products following the intervention and fewer servings of
      vegetable fats (all P<0.05). Only whole-fruit consumption significantly declined
      in the immediate group during the maintenance period (P<0.05). Nutrition
      education can facilitate adoption of a lower-GI diet among free-living people
      with diabetes. Maintaining dietary change likely requires further intervention
      and support.

PMID- 19167962
TI  - College weight gain and behavior transitions: male and female differences.
AB  - College-student weight gain has been well-documented. However, little is known
      about the sex differences in weight gain and related behaviors during the
      transition to college. A repeated-measure study design was used to reveal
      measured weight changes from October to December 2005 among male and female
      college students. Three-hundred seventy-nine college students (60% males)
      participated in both weight assessments and revealed weight gains occurring early
      in college. Weight gains were found to be of greater incidence and magnitude
      among college males in the study. More than 25% of both college males and females
      gained >2.3 kg body weight in an 8-week period. Females starting the study with
      overweight and obese body mass index (calculated as kg/m(2)) scores were less
      likely to gain than either obese or overweight body mass index males or low to
      healthy body mass index students of both sexes. A life-course perspective was
      used to analyze focus group discussions conducted among students who participated
      in the weight assessments and explored their perceptions of the transition in
      eating and exercise behaviors when coming to college. Students described
      struggles in adapting healthful eating and exercise behaviors to college life.
      Comments indicated that while college student activity levels differed from the
      past, there was consistent agreement that eating healthful diets was perceived to
      be a greater challenge in the transition to college. Male students were less
      concerned about weight and used fewer strategies to control weight gain than
      females. More work is needed to understand the transition of behaviors and in
      developing healthful lifestyles during college.

PMID- 19167963
TI  - What does the term "HIV-associated lipodystrophy" mean?

PMID- 19167964
TI  - Deep brain stimulation in psychiatry: concentrating on the road ahead.

PMID- 19167965
TI  - Point-of-care testing, a critical component of laboratory medicine.

PMID- 19167966
TI  - Progress in tissue engineering of soft tissue and organs.

PMID- 19167967
TI  - Learning in a new cardiac surgical center: an analysis of precursor events.
AB  - BACKGROUND: Few studies of learning in the health care sector have analyzed
      measures of process, as opposed to outcomes. We assessed the learning curve for a
      new cardiac surgical center using precursor events (incidents or circumstances
      required for the occurrence of adverse outcomes). METHODS: Intraoperative
      precursor events were recorded prospectively during major adult cardiac
      operations, categorized by blinded adjudicators, and counted for each case
      (overall and according to these categories). Trends in the number of precursor
      events were analyzed by hospital and by defining 10 equal-sized groups across
      time, as were trends in outcomes obtained from institutional databases. Results
      from the first 101 cases performed at a new cardiac surgical site (hospital A)
      were compared with 2 established centers. RESULTS: A steep reduction in the total
      number of precursor events over time was observed in the early experience of
      hospital A (9.2 +/- 4.9 to 2.0 +/- 1.2 events per case, from first to last decile
      of time, P(trend) < .0001) compared with qualitatively stable levels in the other
      hospitals; this reduction was driven largely by decreases in the minor severity
      (P(trend) < .0001), compensated (P(trend) < .0001), and environment (P(trend) <
      .0001) categories of precursor events. No detectable changes over time were
      observed in postoperative mortality and complications. No significant improvement
      was observed in patient comorbid conditions or medical status over time to
      explain the trend in hospital A. CONCLUSION: Analyzing and targeting specific
      kinds of process-related failures (precursor events) may provide a novel and
      sensitive means of tracking, deconstructing, and optimizing organizational
      learning in medicine.

PMID- 19167968
TI  - High-fidelity, simulation-based, interdisciplinary operating room team training
      at the point of care.
AB  - BACKGROUND: The operating room (OR) is a dynamic, high risk setting requiring
      effective teamwork for the safe delivery of care. Teamwork in the modern OR,
      however, is less than ideal. High fidelity simulation is an attractive approach
      to training key teamwork competencies. We have developed a portable simulation
      platform, the mobile mock OR (MMOR) that permits bringing team training over long
      distances to the point of care. We examined the effectiveness of this innovative,
      simulation-based interdisciplinary operating room (OR) team training model on its
      participants. METHODS: All general surgical OR team members at an academic
      affiliated medical center underwent scenario-based training using a mobile mock
      OR. Pre- and post-session mean scores were calculated and analyzed for 15 Likert
      type items measuring self-efficacy in teamwork competencies using t test.
      RESULTS: The mean gain in pre-post item scores for 38 participants averaged 0.4
      units on a 6-point Likert scale. The significance was demonstrated in 4 of the
      items: role clarity (Delta = 0.6 units, P = .02), anticipatory response (Delta =
      0.6 units, P = .01), cross monitoring (Delta = 0.6 units, P < .01), and team
      cohesion and interaction (Delta = 0.7 units, P < .01). CONCLUSION: High-fidelity,
      simulation-based OR team training at the point of care positively impacts self
      efficacy for effective teamwork performance in everyday practice.

PMID- 19167969
TI  - Matrix metalloproteinase-9 derived from polymorphonuclear neutrophils increases
      gut barrier dysfunction and bacterial translocation in rat severe acute
      pancreatitis.
AB  - BACKGROUND: The role of polymorphonuclear neutrophil granulocytes (PMNs) and the
      PMN-derived protease, which is called matrix metalloproteinase-9 (MMP-9), for the
      gut barrier dysfunction in severe acute pancreatitis (SAP) has not yet been
      clarified. The aim of this study was to evaluate the effects of PMNs and MMP-9 on
      gut barrier dysfunction in rat SAP. METHODS: SAP was induced by the injection of
      5% sodium taurocholate, and anti-rat PMN serum or BB-94 were administered 48 h
      and 24 h, respectively, before the induction of acute pancreatitis. Twenty-four
      hours after the induction of acute pancreatitis, the gut barrier dysfunction and
      the incidence of bacterial translocation (BT) and PMN transmigration were
      investigated by bacterial, histologic, and biochemical (MPO) analysis. Inhibition
      of MMP-9 was achieved by depletion of PMNs or inhibition of MMP-activity by a
      broad-spectrum MMP inhibitor and confirmed by zymography. In addition, reactive
      oxygen species were evaluated by spin trap assay. RESULTS: The mucosal injury and
      the infiltration of PMNs into the gut tissue of rats with SAP were significantly
      increased in comparison with rats treated with anti-rat PMN serum or BB-94. The
      levels of MMP-9 and reactive oxygen species in the gut of rats with SAP were
      significantly higher than those of the rats treated with anti-rat PMN serum or BB
      94. Pretreatment with anti-rat PMN serum or BB-94 reduced the incidence of BT in
      SAP. CONCLUSION: The incidence of BT in SAP was prevented by the depletion of
      PMNs or less pronounced by the injection of the MMP inhibitor BB-94. PMNs play an
      important pathophysiologic role in the occurrence of BT, and MMP-9 is involved in
      both BT and PMN transmigration in rat SAP.

PMID- 19167970
TI  - Pretreatment but not treatment with probiotics abolishes mouse intestinal barrier
      dysfunction in acute pancreatitis.
AB  - BACKGROUND: Intestinal barrier failure during acute pancreatitis (AP) is
      associated with translocation of luminal bacteria, resulting in infectious
      complications. We examined the effects of multispecies probiotics on the
      intestinal barrier impairment in a murine model of AP. METHODS: Mice were
      injected with cerulein to induce AP and were sacrificed 11 (early AP) or 72 hours
      (late AP) after start of induction. AP and associated systemic effects were
      confirmed by histology of pancreas and lung. Animals received daily probiotics
      starting 2 days prior to AP induction (pretreatment) or at the moment of AP
      induction (treatment). Mucosal barrier function of the distal ileum was assessed
      in Ussing chambers by measurement of the epithelial electrical resistance and the
      permeability to Na-fluorescein. RESULTS: Histological analysis revealed
      pancreatic injury in both phases of AP, and lung damage in the early phase.
      Epithelial resistance of the ileum was reduced and permeability increased in both
      phases of AP, indicating impairment of the intestinal barrier. Pretreatment had
      no effect on resistance or permeability in the early phase of AP. In the late
      phase of AP, pretreatment but not treatment abolished the AP induced resistance
      decrease and permeability increase. Administration of probiotics as such (ie,
      without induction of AP) had no effect on intestinal barrier function.
      CONCLUSION: Pretreatment with multispecies probiotics for 2 days abolishes
      intestinal barrier dysfunction in the late phase of AP, while treatment does not.
      The effectiveness of probiotics in this model depends on the timing of
      administration. Clinical trials with probiotics should seek conditions where
      treatment can be started prior to onset of disease or elective surgical
      intervention.

PMID- 19167971
TI  - Usefulness of a 13C-labeled mixed triglyceride breath test for assessing
      pancreatic exocrine function after pancreatic surgery.
AB  - BACKGROUND: Although the fecal elastase-1 test is a satisfactory pancreatic
      exocrine function test, breath tests that use stable isotopes have been developed
      recently as alternatives. We evaluated the usefulness of a (13)C-labeled mixed
      triglyceride breath test for assessing pancreatic exocrine function after
      pancreatic surgery. METHODS: The breath test and the fecal elastase-1 test were
      performed on 7 healthy volunteers, 10 patients with chronic pancreatitis, and 95
      patients after pancreatic surgery. The breath test was analyzed with isotope
      ratio mass spectrometry and the cumulative recovery of (13)CO(2) at 7 hours (%
      dose (13)C cum 7h) was calculated. The fecal elastase-1 concentration was
      determined immunoenzymatically. RESULTS: Both the fecal elastase-1 concentration
      and the % dose (13)C cum 7h of chronic pancreatitis patients and pancreatic
      resection patients were less than those of healthy volunteers. In all subjects, %
      dose (13)C cum 7h correlated with the fecal elastase-1 concentration (n = 112,
      R(2) = 0.14, P < .01). Accuracy rates for clinical symptoms, including clinical
      steatorrhea, for the fecal test and the breath test were 62 and 88%,
      respectively. CONCLUSION: The (13)C-labeled mixed triglyceride breath test might
      be more useful than the fecal elastase-1 test for evaluating pancreatic exocrine
      function after pancreatic resection.

PMID- 19167972
TI  - Lymph node dissection in the lateral neck for completion in central node-positive
      papillary thyroid cancer.
AB  - BACKGROUND: In papillary thyroid cancer, quantitative relationships may exist
      between central and lateral neck lymph node metastases, which may be of clinical
      usefulness. METHODS: This comparative analysis of central and lateral neck lymph
      node metastases was undertaken in 88 patients with untreated papillary thyroid
      cancer who underwent compartment-oriented lymph node dissection in the central
      and ipsilateral lateral neck. In 32 of these patients, the contralateral lateral
      neck was dissected in addition. RESULTS: Central lymph node metastases were
      categorized in increments of 0 (22 patients), 1-5 (29 patients), 6-10 (12
      patients), and more than 10 positive nodes (25 patients). With more than 5
      positive nodes, the rates and numbers of lateral lymph node metastases increased
      from between 45% and 69% to 100% and from a mean of between 2 and 3 to between 6
      and 8 lymph node metastases (all P < .001) in the ipsilateral neck; and from
      between 0% and 33% to between 60% and 71% (P = .009) and from a mean of between 0
      and 1 to between 3 and 7 lymph node metastases (P = .003) in the contralateral
      neck. Lateral lymph node metastases in the contralateral neck always coexisted
      with metastases in both the central and the opposite lateral neck. When only
      patients with positive lateral nodes were considered, the successive increase in
      the number of lateral lymph node metastases was still present. Altogether, the
      ipsilateral neck harbored more often lateral lymph node metastasis with more
      positive lateral nodes than the contralateral neck. CONCLUSION: These
      histopathologic associations may provide a foundation for more evidence-based
      decisions regarding lymph node dissection of the lateral neck compartments in
      patients with node-positive papillary thyroid cancer.

PMID- 19167973
TI  - The effect of endoscopic treatment on healing of anastomotic leaks after anterior
      resection of rectal cancer.
AB  - BACKGROUND: Despite surgical advances, anastomotic leaks remain a major
      complication after rectal resection. Endoscopic techniques are increasingly used
      as an alternative or in addition to conventional operative therapy of anastomotic
      leakage. We have analyzed the impact of endoscopic treatment on the outcome of
      patients with leaks after resection of rectal cancer. METHODS: From January 2000
      to December 2005, rectal resection was performed in 274 patients with rectal
      cancer. Anastomotic leakage was observed in 29 patients (11%). Nine of these
      patients received a protective ileostomy. The remaining 20 patients underwent
      either conventional operative or endoscopic treatment. Both groups were analyzed
      regarding complications, necessity of operative reintervention, hospitalization,
      anastomotic healing time, and stoma reversal rate. RESULTS: The endoscopic group
      included 13 patients who underwent endoscopic debridement in combination with
      stenting, endoluminal vacuum therapy, or fibrin injection. The remaining 7
      patients underwent reoperation-secondary ileostomy creation (n = 4), Hartmann
      procedure (n = 2), or anastomotic repair (n = 1). Stoma creation was necessary in
      7 of 13 patients (54%) in the endoscopic group and in 6 of 7 patients (86%) in
      the operative group. There were no significant differences regarding
      postoperative septicemia (39 vs 43%), duration of intensive care (13 vs 11 days),
      or time of hospitalization (25 vs 26 days) for endoscopic and conventional
      therapies. Mean healing time of the anastomotic leak in the endoscopic and
      conventional group was 105 and 173 days, respectively. The stoma reversal rate
      was similar in both groups (50 vs 57%), but the overall rate of patients without
      colostomy was higher in the endoscopic group (77 vs 57%). CONCLUSION: Endoscopic
      therapy in combination with effective operative drainage may support healing of
      anastomotic leaks after rectal resection. However, the majority of patients
      require operative reintervention with bowel diversion despite endoscopic
      treatment.

PMID- 19167974
TI  - Pelvic exenteration for clinical T4 rectal cancer: oncologic outcome in 93
      patients at a single institution over a 30-year period.
AB  - BACKGROUND: Patients with stage T4 rectal cancer are known to have poor survival
      and often require pelvic exenteration (PE). We describe the oncologic outcome of
      PE for patients with clinical T4 rectal cancer over a 30-year period. METHODS:
      Data for 93 patients with primary rectal cancer who underwent PE between 1975 and
      2005 were reviewed retrospectively. RESULTS: Curative resection was performed in
      91 patients (97.9%). Estimated 5-year overall survival (OS) and 5-year recurrence
      free survival (RFS) rates were 52% and 46%, respectively. Irradiation was
      administered in 18 patients (19.4%). Local recurrence was observed in 7 patients,
      of whom 6 had lymph node (LN) involvement. Estimated local recurrence rate at 2
      years was 8.6% (2.0% in node-negative and 16.4% in node-positive patients).
      Multivariate analysis demonstrated that lateral pelvic LN involvement (P = .03),
      a carcinoembryonic antigen level of >10 ng/dL (P = .04), and lymphovascular
      invasion (P = .04) were significantly associated with decreased OS. Only lateral
      pelvic LN involvement was significantly associated with decreased RFS (P = .01).
      CONCLUSION: For patients with clinical T4 rectal cancer, PE can provide an
      opportunity for long-term survival and good local control. Patients with lateral
      pelvic LN involvement should be offered adjuvant treatment pre- or
      postoperatively to improve prognosis after PE.

PMID- 19167976
TI  - Improved hepatocyte function of future liver remnant of cirrhotic rats after
      portal vein ligation: a bonus other than volume shifting.
AB  - BACKGROUND: Preoperative portal vein embolization is increasingly employed for
      those with hepatocellular carcinoma and cirrhosis to gain a volume-shifting
      effect. However, the alterations of histologic architecture and hepatocyte
      function of future liver remnant (FLR) remain unexplored. METHODS: Portal vein
      ligation (PVL) was performed in cirrhotic and noncirrhotic rats. Regeneration
      indices that include the DNA synthesis index, restituted liver mass, and the
      redistributed volume ratio were measured. The indocyanine green 15' retention
      test (ICG-R15), histologic changes, total Knodell score, and activated hepatic
      stellate cells (HSCs) were measured before and after PVL. Tc-99m sulfur-colloid
      liver single photon emission computed tomography (SPECT) and diisopropyl
      iminoacetic acid (DISIDA) SPECT were conducted. RESULTS: The redistributed volume
      ratio of cirrhotic rats was less than noncirrhotic rats (63% vs 80%, P < .01).
      The ICG-R15 of cirrhotic rats at day 7 after PVL was improved compared with
      baseline (6.0 +/- 4.1% vs 15.8 +/- 4.6%, P < .01). The total Knodell score and
      activated HSCs of FLR in cirrhotic rats both were decreased compared with those
      of baseline. The redistributed volume ratio of noncirrhotic and cirrhotic rats
      based on 99mTc sulfur-colloid SPECT were 79% and 64%, respectively. The clearance
      T(1/2) of FLR in cirrhotic rats based on DISIDA SPECT was decreased compared with
      baseline (5.2 +/- 1.9 min vs 8.6 +/- 3.1 min). CONCLUSION: The regenerated
      functional liver mass of cirrhotic rats after PVL is less than noncirrhotic rats,
      whereas the hepatocyte function of FLR in cirrhotic rats is improved relevant to
      tissue remodeling.

PMID- 19167975
TI  - Adhesion prophylaxis using a copolymer with rationally designed material
      properties.
AB  - BACKGROUND: Physical barriers are the only licensed adjuncts for adhesion
      prophylaxis in the United States and Europe. Here, we investigate D,L-polylactide
      epsilon-caprolactonetrimethylenecarbonate (PCT copolymer), which is a rationally
      designed biomaterial, as an adhesion barrier. METHODS: PCT copolymer membranes
      were produced by polymerization of the monomers, dissolution in organic solvents,
      and subsequently processing them by means of modified phase inversion and freeze
      drying. In vitro cytotoxicity was assayed by fibroblast culture. In vivo adhesion
      prophylaxis was studied in a rat model that involved standardized traumatization
      by electrocautery and suturing. The quantity and quality of the resulting
      adhesions were scored 14 days postoperatively. Complete autopsy was performed in
      each animal, and the implantation sites were examined histologically. The
      suitability for human laparoscopic application was investigated in a patient
      admitted for routine myomectomy. RESULTS: The PCT copolymer had no effect on the
      proliferation of cultured cells in vitro. The in vivo model showed that the
      quantity of adhesions that cover the traumatized areas was significantly less in
      animals treated with PCT copolymer membrane (32%) than in untreated animals (78%)
      (P < .01). Adhesions of both dense and filmy quality were affected. In the
      animals, autopsy and histologic examination of the relevant tissues revealed no
      indication of adverse reactions to the PCT copolymer. Human laparoscopic
      application was successful. CONCLUSION: The PCT copolymer membrane is
      biocompatible with the abdominal cavity and decreased adhesions in the animal
      model. It is also suitable for human laparoscopic application. Therefore, the PCT
      copolymer represents a candidate for additional clinical evaluation.

PMID- 19167977
TI  - Dual grafts in adult-to-adult living donor liver transplantation: a single center
      experience in Taiwan.
AB  - Volume mismatch is encountered when a single live donor cannot provide adequate
      graft volume to the recipient with a remnant liver volume which is safe for
      donation. Our objective is to present our experience in living donor liver
      transplantation using dual grafts. Record review of 4 dual graft recipients was
      done. The results were compared with 122 consecutive patients who received a
      single right lobe. All dual graft recipients were surviving with satisfactory
      liver function at a median follow-up of 21 months. Two recipients received 1
      right and 1 left lobe graft, while the other 2 recipients received 2 left lobe
      grafts. One donor developed biloma and was managed by percutaneous drainage. The
      first recipient required re-laparotomy for postoperative bleeding. The second
      recipient underwent re-laparotomy for bile leak. The third recipient developed
      grade II decubitus ulcers due to a prolonged sedentary position. When compared
      with recipients who received a single right lobe, the operative time was
      prolonged in the dual graft group. There was no apparent increase in the rate of
      vascular and biliary complications or the incidence of acute cellular rejection.
      Actuarial patient survivals were comparable in both groups. Dual graft
      transplantation provides sufficient volume in the recipient without jeopardizing
      donor safety.

PMID- 19167978
TI  - Mitomycin C decreases the rate of stricture formation in caustic esophageal burns
      in rats.
AB  - BACKGROUND: Although the incidence of caustic ingestion is declining, the
      management of caustic esophageal strictures remains a challenge. Although many
      agents have been tried experimentally to treat strictures, few have gained
      clinical application. The aim of this study was to investigate the influence of
      mitomycin C (MMC), which inhibits fibroblastic proliferation in treating delayed
      caustic esophageal strictures. METHODS: Forty-two rats were allocated into 3
      groups. Caustic esophageal burns were created as described by Gehanno. Group A
      was instilled only with saline. Group B was injured with 10% NaOH and left
      untreated. Group C was injured and received topical MMC at 0.04% concentration in
      the fourth week. At 56 days, stenosis index (SI), collagen deposition, and
      hydroxyproline content (HP) were determined in distal esophageal segments.
      Statistical analyses were performed. RESULTS: The mean SI in group B was
      significantly higher than others (SI: 1.15 +/- 0.37 d/lum, P < .05). Collagen
      accumulation was highest in group B, followed by groups C and A, respectively.
      Collagen deposition in group C was statistically lower than group B (P < .018).
      The mean HP in group B was statistically higher than others (5.07 +/- 1.30
      microg/mg tissue, P < .05), and similar between groups A and C (1.20 +/- 0.20,
      1.91+/- 0.79, respectively, P = .73). CONCLUSION: In the current study, MMC
      treatment ameliorated caustic esophageal stricture as reflected in the
      significantly lower SI. We conclude that MMC application is effective in the
      treatment of caustic esophageal strictures.

PMID- 19167979
TI  - Role of extracellular signal-regulated protein kinase (ERK) in 17beta-estradiol
      mediated attenuation of lung injury after trauma-hemorrhage.
AB  - BACKGROUND: Extracellular signal-regulated protein kinase (ERK) is known to be
      involved in pro-inflammatory and chemotactic events in response to injury. The
      aim of this study is to elucidate whether ERK plays any role in 17beta-estradiol
      (E2)-mediated attenuation of lung injury and pro-inflammatory mediators after
      trauma-hemorrhage. METHODS: Male Sprague-Dawley rats underwent trauma-hemorrhage
      (mean blood pressure approximately 40 mm Hg for 90 min) followed by fluid
      resuscitation. At the onset of resuscitation, rats were treated with vehicle
      (cyclodextrin), E2 (1 mg/kg body weight [BW]), or the ERK inhibitor PD98059 (2
      mg/kg BW). At 2 h after sham operation or trauma-hemorrhage, various parameters
      were measured. RESULTS: Trauma-hemorrhage led to a significant increase in lung
      ERK phosphorylation, which was associated with increased lung myeloperoxidase
      activity, wet-to-dry weight ratio, interleukin (IL)-6, tumor necrosis factor
      (TNF)-alpha, intercellular adhesion molecule (ICAM)-1, cytokine-induced
      neutrophil chemoattractant (CINC)-1, and macrophage inflammatory protein-2
      levels. Circulatory IL-6, TNF-alpha, and lactate levels were also increased after
      trauma-hemorrhage compared with shams. Administration of E2 or ERK inhibitor
      PD98059 after trauma-hemorrhage attenuated the trauma-hemorrhage-induced increase
      in lung injury markers, ERK phosphorylation and cytokines/chemokines, ICAM-1
      production, as well as circulatory cytokines and lactate levels. CONCLUSION:
      These results collectively suggest that the salutary effects of E2 on the lung
      after trauma-hemorrhage are mediated via an ERK pathway and subsequent
      downregulation of pro-inflammatory mediator production.

PMID- 19167980
TI  - beta2 Adrenoreceptor blockade attenuates the hyperinflammatory response induced
      by traumatic injury.
AB  - BACKGROUND: Major operative injury initiates immunologic changes that may result
      in a systemic inflammatory response, leading to organ dysfunction/sepsis.
      Catecholamines seem to be key mediators. The effects of beta(2) receptor blockade
      in vitro and in vivo before and after operative injury were studied to clarify
      their role. METHODS: In vitro studies were done in RAW 264.7 cells using
      epinephrine (50 micromol/L) with or without alpha(2)- and beta(2)-receptor
      blockade. Comparative gene expression analysis on the Toll-like receptor (TLR)-4
      receptor signaling pathway was performed between RAW cells pretreated with
      epinephrine with subsequent lipopolysaccharide (LPS) stimulation versus LPS
      alone. Confirmatory studies were performed by real-time reverse transcription
      polymerase chain reaction (RT-PCR). Tumor necrosis factor (TNF)-alpha gene and
      protein expression were determined via real time RT-PCR and enzyme-linked
      immunosorbent assay, respectively. In vivo, Balb/C mice received no treatment nor
      injury (group I). Group II received operative injury and vehicle injection, group
      III received ICI 118,551 (beta(2)-receptor antagonist) 30 minutes before or in
      separate studies after operative injury. At 7 days, splenic macrophages were
      harvested and cytokine production was measured with or without LPS. In separate
      experiments, cecal ligation and puncture (CLP) was done 7 days after operation
      and survival determined. RESULTS: In vitro studies demonstrated that epinephrine
      pretreatment significantly increased TNF-alpha production with LPS stimulation (P
      < .05). beta(2)-Receptor blockade significantly attenuated (P < .05) LPS
      stimulated TNF-alpha production. MD-2, an essential coactivator of TLR-4
      signaling, gene expression was significantly elevated when cells were pretreated
      with epinephrine before LPS exposure (P < .001). In vivo studies demonstrated a
      significant decrease (P < .05) in TNF-alpha and interleukin-6 production in the
      ICI 118,551 group. Similar findings were demonstrated measuring monocyte
      chemoattractant protein-1 and interferon-gamma cytokine levels (P < .05) versus
      no treatment. ICI 118,551 treatment 30 minutes before operation demonstrated a
      31% reduction in mortality after CLP (P < .05). CONCLUSION: This study
      demonstrates that beta(2)-receptor blockade reduces macrophage cytokine
      production and improves survival showing the critical importance of
      catecholamines to the immunologic response in surgery.

PMID- 19167981
TI  - Malignant transformation of a pilonidal sinus.

PMID- 19167982
TI  - Giant cavernous hemangioma of the liver with coagulopathy: adult Kasabach-Merritt
      syndrome.

PMID- 19167983
TI  - Minimally invasive treatment for spontaneous mediastinal hematoma.

PMID- 19167985
TI  - The extent of parathyroidectomy for HRPT2-related hyperparathyroidism.

PMID- 19167986
TI  - Electromagnetic effects - From cell biology to medicine.
AB  - In this review we compile and discuss the published plethora of cell biological
      effects which are ascribed to electric fields (EF), magnetic fields (MF) and
      electromagnetic fields (EMF). In recent years, a change in paradigm took place
      concerning the endogenously produced static EF of cells and tissues. Here, modern
      molecular biology could link the action of ion transporters and ion channels to
      the "electric" action of cells and tissues. Also, sensing of these mainly EF
      could be demonstrated in studies of cell migration and wound healing. The
      triggers exerted by ion concentrations and concomitant electric field gradients
      have been traced along signaling cascades till gene expression changes in the
      nucleus. Far more enigmatic is the way of action of static MF which come in most
      cases from outside (e.g. earth magnetic field). All systems in an organism from
      the molecular to the organ level are more or less in motion. Thus, in living
      tissue we mostly find alternating fields as well as combination of EF and MF
      normally in the range of extremely low-frequency EMF. Because a bewildering array
      of model systems and clinical devices exits in the EMF field we concentrate on
      cell biological findings and look for basic principles in the EF, MF and EMF
      action. As an outlook for future research topics, this review tries to link areas
      of EF, MF and EMF research to thermodynamics and quantum physics, approaches that
      will produce novel insights into cell biology.

PMID- 19167987
TI  - The immunologic effect of TGF-beta1 chitosan nanoparticle plasmids on ovalbumin
      induced allergic BALB/c mice.
AB  - Studies suggested that an increased transforming growth factor-beta (TGF-beta)
      level in the intestinal tract helps to alleviate symptoms of food allergy. An
      efficient method for in vivo delivery of TGF-beta is yet to be developed. In this
      report, we investigated some DNA-based therapeutic strategies. Our results
      demonstrate that a sustainable increase of TGF-beta protein in mouse intestinal
      tissue can be induced after oral administration by gavage of a TGF-beta
      expressing DNA vector that was packed in chitosan nanoparticles. Concomitantly, a
      significant amelioration of ovalbumin-induced food allergy symptoms was observed.
      Thus, our study supports this therapy being perhaps a better alternative to the
      previously reported protein-based strategies.

PMID- 19167988
TI  - Identification of regulatory T cells during experimental Leishmania infantum
      infection.
AB  - Leishmania infantum is the causative agent of zoonotic visceral leishmaniasis
      (ZVL), a disease frequently characterized by specific impairment of cell-mediated
      immune responses and uncontrolled parasitization. Regulatory T cells (Treg) have
      been shown to be involved in the direct induction of immunosuppression of
      effector immune response during chronic Leishmania infections. The present study
      aims to investigate the possible involvement of Treg cells during L. infantum
      infection. Results indicate that CD4(+)CD25(+) regulatory T cells are present in
      L. infantum-infected BALB/c mice and exhibit phenotypic and functional
      characteristics of Treg. The presence of high levels of Foxp3 gene expression and
      surface expression of alpha(E)beta(7) integrin (CD103) suggest a predisposition
      for Treg retention within sites of L. infantum infection, as is the case of the
      spleen and draining lymph nodes, consequently influencing local immune response.
      Th1 and Th2 effector immune responses seem inadequate, due to Treg expansion.
      Foxp3 expressing CD4(+)CD25(+) T cells are capable of producing TGF-beta and may
      contribute to immunosuppression and better control of parasite-mediated
      immunopathology during infection. Surprisingly, IL-10 producing-CD4(+)CD25(
      )Foxp3(-) T cells were also identified as an additional source of IL-10 and may
      represent a type 1 regulatory T (Tr1) cell subset that is being induced by L.
      infantum parasites. These findings suggest that distinct regulatory T cells
      develop in response to L. infantum and may play a possible role in promoting
      parasite persistence and the establishment of chronic infection.

PMID- 19167989
TI  - Cloning, expression and immunogenicity of the translation initiation factor 3
      homologue of Brucella abortus.
AB  - The infC gene of Brucella abortus encoding the translation initiation factor 3
      (IF3) was cloned, sequenced and expressed in Escherichia coli. The amino acid
      sequence analysis predicted a product with 74-80% identity with the IF3 proteins
      from Mesorhizobium loti, Sinorhizobium meliloti, Aurantimona sp. and
      Mesorhizobium sp. This protein also show 54% amino acid sequence identity with
      the E. coli IF3, sharing most of the residues which were described as responsible
      for the biological activity of this protein. Since we have previously reported
      the immunoprotective capacity of this Brucella protein, we stimulated lymphoid
      cells from animals immunized with purified recombinant Brucella IF3 protein "in
      vitro" with this antigen. The lymphocytes were able to mount a strong
      proliferative response with concomitant production of gamma interferon, but
      without the secretion of either IL-4 or antibodies. Thus, immunization with the
      Brucella recombinant IF3 protein promotes a TH-1 polarized response, allowing us
      to propose it as a promising candidate antigen for the development of subunit
      vaccines against Brucella.

PMID- 19167990
TI  - Acute immunomodulatory effects of iron polyisomaltosate in rats.
AB  - Anti-anaemic drug ferric-sorbitol citrate showed immunomodulatory effects,
      activating NF-kappaB in peritoneal macrophages, which consequently secrete tumour
      necrosis factor-alpha (TNF-alpha). TNF-alpha activates NF-kappaB in spleen cells.
      The aim of this study was to investigate the effect of iron polyisomaltosate, an
      iron (Fe(3+)) compound, on serum iron, interleukin-6 (IL-6) and serotonin (5-HT)
      concentration, neutrophil activity, and NF-kappaB activation in peritoneal
      macrophages and spleen cells in rats. Female Wistar rats were injected i.p. with
      7.5mg iron/kg of iron polyisomaltosate 1.5, 3, 6, 24 and 48h before sacrifice.
      Serum iron, 5-HT and IL-6 concentration was determined by colorimetric,
      spectrofluorimetric and ELISA methods, neutrophil activity by a chemiluminescence
      assay, and NF-kappaB expression/activation by a Dot-Blot method. Iron
      polyisomaltosate significantly increased serum iron and 5-HT concentrations
      during the first 6h, IL-6 levels 3 and 6h, and diminished respiratory burst of
      granulocytes 1.5h after the injection. Iron polyisomaltosate stimulated
      activation of p65, p50 and RelB subunits of NF-kappaB in the peritoneal
      macrophages after 6h, and RelB subunit was additionally increased after 24 and
      48h. In the spleen cells iron polyisomaltosate stimulated p65 subunit after 48h
      and RelB subunit after 24h. The results showed time-dependent immunomodulatory
      effects of iron polyisomaltosate. These effects might be achieved via induction
      of the intracellular signalling for NF-kappaB activation in peritoneal
      macrophages and later in spleen cells, together with increase of serum 5-HT, and
      IL-6 but with diminished respiratory burst of granulocytes. Iron polyisomaltosate
      presumably activated reactive oxygen species resulting in the stimulation of the
      acute phase reactants in the liver.

PMID- 19167991
TI  - Immunomodulatory effects of Turkish propolis: changes in neopterin release and
      tryptophan degradation.
AB  - In most of the diseases which are considered to benefit from propolis, cellular
      immune reaction is activated, neopterin levels in body fluids are increased and
      enhanced tryptophan degradation is observed. In this study, the immunomodulatory
      effects of six Turkish propolis samples were evaluated by using the in vitro
      model of peripheral blood mononuclear cells (PBMC). Concentrations of neopterin,
      tryptophan, kynurenine and pro-inflammatory cytokines, tumor necrosis factor
      alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were determined and also the
      viability of the cells was checked with trypan blue and MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. In PBMC treated with
      mitogen phytohaemagglutinin, neopterin production and tryptophan degradation by
      enzyme indoleamine 2,3-dioxygenase (IDO) as well as release of cytokines was
      significantly enhanced and upon treatment with propolis extracts all these
      effects were dose-dependently suppressed. Results show an immunomodulatory effect
      of propolis extracts which includes down-regulation of IDO activity. IDO enzyme
      is considered to play an important role in the development of immunodeficiency
      and neuropsychiatric symptoms in patient with chronic inflammation. The
      suppression of tryptophan degradation by propolis extracts may therefore be
      related with some of its beneficial health properties in humans.

PMID- 19167992
TI  - Plasma cytokine concentration changes induced by the antitumor agents dipterinyl
      calcium pentahydrate (DCP) and related calcium pterins.
AB  - Analysis of plasma cytokine concentration changes determined that oral dosing
      with the antitumor agent (1:4 mol:mol) calcium pterin (CaPterin) increased plasma
      IL-10, decreased plasma IL-6, and decreased plasma IFN-gamma concentrations in
      nude mice with MDA-MB-231 xenograph tumors [Moheno, P., Pfleiderer, W.,
      Dipasquale, A.G., Rheingold, A.L., Fuchs, D., 2008. Cytokine and IDO metabolite
      changes effected by calcium pterin during inhibition of MDA-MB-231 xenograph
      tumors in nude mice. Int. J. Pharm. 355, 238-248]. A further analysis, reported
      here, of plasma cytokine concentration changes in nude mice with the same tumor
      xenographs treated with dipterinyl calcium pentahydrate (DCP), (1:2 mol:mol)
      calcium pterin, and CaCl(2).2H(2)O has been carried out. The measured cytokines
      included: IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-gamma, and TNF-alpha. The
      major preliminary findings from the analyses of these data are that (1) the
      overall relative tumor volumes for the treatments correlated significantly with a
      full study antitumor plasma cytokine pattern (fsAPCP), a composite measure
      consisting of decreased plasma IL-6 and increased IL-4 concentrations, and (2)
      DCP induces a significant threshold antitumor response strongly correlated to a
      derived DCP antitumor plasma cytokine pattern (DCP/APCP) consisting of plasma IL
      12, IL-6, and IL-4 concentration changes. This DCP/APCP composite measure
      identifies plasma IL-12 concentration increases, plasma IL-6 concentration
      decreases, and plasma IL-4 concentration increases correlated to relative tumor
      volume decreases caused by DCP dosing. The finding that the novel calcium pterins
      and CaCl(2).2H(2)O treatments decrease plasma IL-6 concentrations corroborates
      the previous finding that CaPterin dosing decreases plasma IL-6 concentrations in
      this mouse/tumor system [Moheno, P., Pfleiderer, W., Dipasquale, A.G., Rheingold,
      A.L., Fuchs, D., 2008. Cytokine and IDO metabolite changes effected by calcium
      pterin during inhibition of MDA-MB-231 xenograph tumors in nude mice. Int. J.
      Pharm. 355, 238-248].

PMID- 19167993
TI  - Free intracellular Ca2+ regulates bacterial lipopolysaccharide induction of iNOS
      in human macrophages.
AB  - Inducible nitric oxide synthase (iNOS) reaction is of enormous significance in
      innate immune protective response of host to microbial challenges. We speculate
      that microbial challenges, by virtue of their lipopolysaccharide (LPS) content,
      exert an effect on intracellular free Ca(2+) levels ([Ca(2+)]i), which evokes
      cellular signaling in a manner that depends on LPS type. In this study, we
      investigated the effect of LPS from heterogeneous sources (Chlamydia pneumoniae
      [cLPS], Pseudomonas aeruginosa [pLPS], and Salmonella typhimurium [sLPS]) on
      nitric oxide (NO) release and iNOS expression in THP-1- and U937-derived
      macrophages, and determined the role of free [Ca(2+)]i on LPS-mediated generation
      of NO and iNOS expression in these cell types. The role of free [Ca(2+)]i
      oscillation and the probable input of extracellular Ca(2+) influx on Ca(2+)
      signals was monitored in relation to iNOS expression in LPS-stimulated
      macrophages. There was a significant difference in the time course release of NO
      in both macrophage types when stimulated with cLPS, or pLPS, or sLPS. In all
      instances, LPS induced a significant release of NO compared with interferon
      gamma. There was a difference in the pattern of basal iNOS reaction leading to NO
      release compared to iNOS expression observed at 24h post-stimulation. While a
      biphasic pattern was observed in the manner in which free [Ca(2+)]i affected iNOS
      expression, inhibition of extracellular Ca(2+) influx resulted in a steady
      increase in iNOS expression. The implications of these findings are: moderate
      free [Ca(2+)]i affects macrophage release of NO and iNOS expression during LPS
      stimulation; also, LPS of heterogeneous sources differentially evokes macrophage
      iNOS reactions irrespective of macrophage types.

PMID- 19167994
TI  - CD137L- and RANKL-mediated reverse signals inhibit osteoclastogenesis and T
      lymphocyte proliferation.
AB  - Members of the tumor necrosis factor-related family of ligands and receptors
      appear to be critical regulators of osteoclastogenesis and various cellular
      responses in T cells. In the present study, we have investigated CD137L and RANKL
      (receptor activator of nuclear factor (NF)-kappaB ligand)-induced biological
      responses in osteoclasts and T cells, respectively. Osteoclast-like cells were
      generated from murine bone marrow in the presence of RANKL and monocyte
      macrophage colony-stimulating factor (M-CSF). RAW264.7 cells (murine monocytic
      cell line) constitutively express CD137L. Ligation of CD137L with anti-CD137L mAb
      (TKS-1) inhibits RANKL-induced osteoclast formation in a dose-dependent manner.
      Bone marrow cells expressed CD137L only when induced by treatment with M-CSF. In
      bone marrow cells, cross-linking of CD137L with anti-CD137L mAb (TKS-1) inhibits
      M-CSF/RANKL-evoked formation of multi-nucleated osteoclasts. Further we examined
      RANKL-mediated regulation of T cell proliferation. Both mouse CD4(+) and CD8(+) T
      cells expressed RANKL following their activation by anti-CD3 Ab and anti-CD137
      Ab. Ligation of RANKL with OPG-Fc, the decoy receptor for RANKL, inhibited both
      mouse CD4(+) and CD8(+) T cell proliferation. From the above results, we suggest
      that the cellular responses in cell-to-cell interactions between T cells and
      osteoclasts are regulated through reciprocal regulations of CD137/CD137L and
      RANK/RANKL interactions.

PMID- 19167995
TI  - Nutraceuticals: Part II.

PMID- 19167996
TI  - The internal and external use of medicinal plants.
AB  - The term "cosmeceutical" is not defined in terms of the law. A review of some of
      the more commonly used dietary supplements and their chemistry and topical use
      confirms that there is merit in using these plants both internally and
      externally. The role of flavonoids, isoflavones, phytosterol, and plant hormone
      related chemicals are examined for their physiological effect.

PMID- 19167997
TI  - Virgin olive oil as a fundamental nutritional component and skin protector.
AB  - Fats are indispensable to life not only as an energy source but also for their
      structural role in the skin, retina, nervous system, lipoproteins, and biologic
      membranes. They are also precursors of important hormones and constitute the
      vehicle for the absorption of liposoluble vitamins. Nutritionists recommend a
      balanced lipid intake corresponding to a total amount of fats equal to 25% to 30%
      of total calories with a ratio in monounsaturated and polyunsaturated fatty
      acids. Thus, olive oil, with its balanced fatty acid composition, is of high
      nutritional value. Moreover, extra virgin olive oil, extracted from a fruit, has
      an important value related to the antioxidant power of minor components. Extra
      virgin olive oil contains 98% to 99% triglycerides and 1% to 2% minor components.
      In the triglycerides, the main fatty acids are represented by monounsaturates
      (oleic), with a slight amount of saturates and an adequate amount of
      polyunsaturates. The minor components are alpha-tocopherol, phenol compounds,
      carotenoids, squalene, phytosterols, and chlorophyll. Factors that can influence
      olive oil's composition, especially in regard to its minor components, are the
      cultivar, area of production, time of harvesting, and degree of technology used
      in its production. Therefore, an evaluation of the biologic value of extra virgin
      olive oil and its use as a topical raw material in cosmetic dermatology is
      reported.

PMID- 19167998
TI  - The photoprotective activity of nutraceuticals.
AB  - Nutrition plays an important role in the treatment of many diseases, and the
      right choice of nutrients can help to prevent disorders and improve the quality
      of life. Epidemiologic studies suggest that there is a close relationship between
      ultraviolet exposure (high level of reactive oxygen species) and the intake of
      specific dietary factors (eg antioxidants), and the diminished risk of developing
      cancer, coronary heart disease, or cataracts. Free radicals and reactive oxygen
      species are synthesized endogenously (eg, in energy metabolism and the
      antimicrobial defense system of the body) or produced as reactions to exogenous
      exposure (eg, cigarette smoke, imbalanced diet, exhaustive exercise,
      environmental pollutants, and food contaminants). Human dietary intervention
      studies based on the use of antioxidant compounds show how they can protect from
      endogenous and exogenous environmental assaults, and neutralize sun-induced
      effects on the skin. The future challenge will be to combine the strategic use of
      cosmeceuticals and nutraceuticals in preventing the damaging effects of
      ultraviolet radiation and environmental pollutants on the many biologic processes
      involving skin aging and cancer.

PMID- 19167999
TI  - Antioxidant use in nutraceuticals.
AB  - The focus of this contribution is oxidation generated by oxygen and by all other
      reactive species, with an emphasis on reactive oxygen species. This study
      considers the different pathways that generate oxidative stress, which is a
      physiologic process that can become dangerous if becomes excessive and overcomes
      the reserve of antioxidants. Some of the most important methods to determine
      oxidative stress in plasma, both in humans and in experimental animals, are
      discussed; particular attention is given to the d-ROMs test, which detects the
      hydroperoxides in plasma and is a very simple and reliable method. The
      antioxidant hierarchy also is discussed to indicate the most powerful
      physiological antioxidant and those derived from food intake or supplementation.
      As every antioxidant also can be a pro-oxidant, indications are given about their
      use and how to avoid the administration of high dosages of a single antioxidant.

PMID- 19168000
TI  - Lutein and zeaxanthin in eye and skin health.
AB  - Less than 20 of the hundreds of carotenoids found in nature are found in the
      human body. These carotenoids are present in the body from the foods or dietary
      supplements that humans consume. The body does not synthesize them. Among the
      carotenoids present in the body, only lutein and its coexistent isomer,
      zeaxanthin, are found in that portion of the eye where light is focused by the
      lens, namely, the macula lutea. Numerous studies have shown that lutein and
      zeaxanthin may provide significant protection against the potential damage caused
      by light striking this portion of the retina. In the eye, lutein and zeaxanthin
      have been shown to filter high-energy wavelengths of visible light and act as
      antioxidants to protect against the formation of reactive oxygen species and
      subsequent free radicals. Human studies have demonstrated that lutein and
      zeaxanthin are present in the skin, and animal studies have provided evidence of
      significant efficacy against light-induced skin damage, especially the
      ultraviolet wavelengths. Little was known about the protective effects of these
      carotenoids in human skin until recently. This article reviews the scientific
      literature pertaining to the effects that lutein and zeaxanthin exhibit in the
      human eye and skin.

PMID- 19168001
TI  - Melatonin: circadian rhythm regulator, chronobiotic, antioxidant and beyond.
AB  - For many years, melatonin has been known to interact with circadian rhythms. New
      evidence indicates that melatonin acts as a free radical scavenger and
      antioxidant. Moreover, melatonin prevents apoptosis in different types of cells,
      because it induces mRNA levels of several antioxidant enzymes. It is evident that
      melatonin is involved in the cellular bioenergetic system as a mechanism that
      counteracts the progression of Alzheimer's disease.

PMID- 19168002
TI  - Novel botanical ingredients for beverages.
AB  - Natural substances are generally preferred over chemical ones and are generally
      seen as healthy. The increasing demand for natural ingredients, improving health
      and appearance, is also attracting beverages as the fastest growing segment on
      the functional food market. Functional beverages are launched as fortified water,
      tea, diary or juices claiming overall nutrition, energy, anti-aging or relaxing
      effects. The substitution of so called superfruits, such as berries, grapes, or
      pomegranate delivers an effective range of beneficial compounds, including
      vitamins, fatty acids, minerals, and anti-oxidants. In this context, new exotic
      and African fruits could be useful sources in the near future. Teas and green
      botanicals, such as algae or aloe vera are also rich in effective bioactives and
      have been used traditionally. The botanical kingdom offers endless possibilities.

PMID- 19168003
TI  - Ascorbigen: chemistry, occurrence, and biologic properties.
AB  - Ascorbigen (ABG) belongs to the glucosinolate family and occurs mainly in
      Brassica vegetables. It is formed by its precursor glucobrassicin. Glucobrassicin
      is enzymatically hydrolyzed to indole-3-carbinol, which in turn reacts with L
      ascorbic acid to ABG. The degradation of glucobrassicin is induced by plant
      tissue disruption. The ABG formation depends on pH and temperature. The
      degradation of ABG in acidic medium causes a release of l-ascorbic acid and a
      formation of methylideneindolenine; in more alkaline medium, the degradation of
      ABG causes the formation of 1-deoxy-1-(3-indolyl)-alpha-L-sorbopyranose and 1
      deoxy-1-(3-indolyl)-alpha-l-tagatopyranose. ABG may partly mediate the known
      anticarcinogenic effect of diets rich in Brassicacae. Furthermore, ABG is able to
      induce phase I and II enzymes that are centrally involved in the detoxification
      of xenobiotics. Cosmeceuticals containing ABG as an active principle are becoming
      increasingly popular, although the underlying cellular and molecular mechanisms
      regarding its potential antiaging and ultraviolet-protective properties have not
      been fully established.

PMID- 19168004
TI  - Redox ingredients for oxidative stress prevention: the unexplored potentiality of
      coffee.
AB  - Plant-based foods (such as fruit and vegetables, wine, nuts, natural vegetable
      oils, and whole grains) are an important component of traditional diets in
      Mediterranean regions. A large, consistent body of scientific evidence
      demonstrates that diets rich in plant foods provide protection against
      degenerative diseases; however, despite the consensus of the evidence about the
      health effect of plant foods, it is unclear which components of plant-based foods
      are protective and what their mechanism of action is. One of the hypotheses
      postulated to explain the protective effect of plant food, the antioxidant
      hypothesis, is based on their high content of bioactive molecules. Recent
      evidence suggests that it is the variegate composition of the plant food, an
      optimal mixture of different antioxidants endowed with complementary mechanism of
      action and different redox potential, which is at the basis of their effect on
      health. The global antioxidant efficiency of complex matrixes can be assessed by
      measuring their total antioxidant capacity (TAC) representing the result of
      variables such as redox potentials of the compounds present in the matrix and
      their cumulative and synergistic interaction. In the last years different
      databases for TAC of plant foods have been developed. Results suggest that coffee
      might represent a potential contributor to dietary antioxidant intake. In this
      contribution after describing the main contributors to dietary TAC for different
      plant food group, we will discuss the potentiality of coffee as a source of
      "ready to drink" reducing equivalents.

PMID- 19168005
TI  - Glycemic index, glycemic load, wellness and beauty: the state of the art.
AB  - The glycemic index (GI) is a ranking system for carbohydrates' effect on blood
      glucose levels. It compares available carbohydrates gram for gram in individual
      foods, providing a numerical, evidence-based index of postprandial glycemia. The
      glycemic load (GL) is a ranking system for carbohydrate content in food portions
      based on their GI and the portion size. These two markers increasingly are being
      used to prevent typical diseases of the Western world, including type 2 diabetes
      mellitus, cardiovascular disease, obesity, metabolic syndrome, and acne. Data on
      the efficacy of GI and GL in the treatment of Western population diseases are
      discussed and critically evaluated, with a particular focus on acne and other
      skin disorders.

PMID- 19168006
TI  - Rudi Harold Cormane (1925-1987): a fabulous researcher and clinician.

PMID- 19168007
TI  - Vignettes of a fair skinned Mexican: cultural influences and traditional
      therapies.

PMID- 19168008
TI  - [Results of nephron-sparing surgery for renal cell carcinoma of more than 4 cm in
      diameter].
AB  - To date, radical nephrectomy (RN) remains the gold standard treatment for renal
      cell carcinoma (RCC) larger than 4 cm. However, from the early 1990's,
      improvements in surgical techniques have lead to the development of nephron
      sparing surgery (NSS) for small renal tumours of less than 4 cm in diameter. This
      surgical procedure avoids nephronic waste with an acceptable morbidity and
      similar oncological outcomes compared to radical surgery. Recent large published
      series did not show any difference between NSS and RN in terms of oncological
      safety. Specific and disease-free five-year survival rates (82% to 97.3% and 81%
      to 97.3%, respectively) have confirmed the safety of NSS. Regarding laparoscopic
      NSS, the technique is still under evaluation and only mid-term outcomes are
      available so far. However, these studies are still limited and longer follow-up
      is needed before any definitive statement can be made. Current guidelines
      recommend NSS only in case of RCC of less than 4 cm in diameter in elective
      indications. In daily practice however, surgical teams are pushing back the limit
      above the threshold of 4 cm. More and more surgeons are either considering
      anatomical location or technical expected difficulties rather than just the
      tumour size. NSS leads to higher risk of bleeding, especially in case of tumours
      larger than 4 cm. Therefore, it is absolutely necessary to investigate thoroughly
      the vascularization of the tumour to avoid such complications with exhaustive and
      accurate preoperative imaging.

PMID- 19168009
TI  - [Fournier's gangrene: a review of the recent literature].
AB  - Fournier's gangrene is a rapidly progressive necrotizing fasciitis of the
      perineum and external-genital organs. It is secondary to polymicrobial infection
      by aerobic and anaerobic bacteria with a synergistic action. The aetiology is
      identified in 95% of cases. The source of infection is either cutaneous,
      urogenital or colorectal. Predisposing factors, such as age, diabetes and
      immunodepression, are often present in affected patients. Urgent and aggressive
      treatment is essential to ensure the patient's survival. Treatment consists of
      restoration of the fluid and electrolyte balance and broad-spectrum antibiotic
      therapy rapidly followed by surgical debridement. However, the mortality remains
      high, about 20 to 80%, frequently, due to delayed diagnosis and management.
      Patients who survive the infection require reconstructive surgery with sometimes
      marked sequelae related to the extent of fasciitis and debridement.

PMID- 19168010
TI  - [State of the art and advances in radiotherapy for bladder cancer].
AB  - Radical cystectomy is the treatment of choice for nonmetastatic, muscle
      infiltrating bladder cancer. However, bladder-sparing approaches can be discussed
      in carefully selected patients. Bladder-preservation protocols aim to guaranty
      local control and survival with a functional bladder and a good quality of life.
      Such strategies include combinations of transurethral resection and
      radiochemotherapy, partial cystectomy and brachytherapy, radiotherapy-cystotomy
      and electrontherapy. Strict selection criteria and close follow-up are mandatory.
      New irradiation techniques hold the promise to improve local control by
      selectively boosting the dose to the tumor while better sparing the organs at
      risk. Such advances include the use of multimodal imaging, image-guided
      radiotherapy, concomitant boost with conformal irradiation+/-intensity modulated
      radiation therapy. Brachytherapy, either high-dose or pulsed-rate, is a promising
      technique for selected cases. Highly-conformal irradiation with tumor tracking
      using the Cyberknifetrade mark technology may also provide opportunities to boost
      the tumor while reducing toxicities. Specific innovative irradiation techniques
      are discussed.

PMID- 19168012
TI  - [Extraparenchymental distribution and feasibility of selective clamping of
      segmental renal arteries during partial nephrectomy: a study of the dissection of
      30 kidneys from recent nonformolised corpses].
AB  - OBJECTIVE: To assess the feasibility of selective clamping of segmental renal
      arteries during partial nephrectomy, in order to limit renal infarction to the
      pathological area to be resected. MATERIALS AND METHODS: A dissection of renal
      artery and its extraparenchymal branches was realised. The study included 30
      kidneys from recent nonformolised corpses. The size, distribution, and
      accessibility of the arteries were considered. All the corpses underwent a
      lombotomy with or without rib resection. RESULTS: The majority of dissected
      kidneys had a unique artery (96.66% of cases). The number of segmental arteries
      was zero in five cases (16.66%), one in four cases (13.33%), two in four cases
      (13.33%), three in one case (3%), four in 15 cases (50%) and five in five cases
      (16.66%). The posterior and inferior segmental arteries were more accessible to
      isolate with a respective ratio of 94 and 100% at segmental level. Apical and
      middle segmental arteries were least accessible with a respective ratio of 73 and
      80%. The majority of accidents during dissection occurred with the middle
      segmental artery (62.5% of vascular lesions). CONCLUSION: This anatomic
      dissection on corpses showed that selective renal segmental arteries is possible
      in the majority of cases. This dissection is better indicated in partial
      nephrectomies for renal tumours located posteriorly or in the lower pole.

PMID- 19168011
TI  - [Nephron sparing surgery for renal tumors on a solitary kidney: oncological
      outcomes and long-term functional evolution].
AB  - OBJECTIVE: Nephron sparing surgery raises the challenge of avoiding chronic
      haemodialysis for patients having malignancies on a solitary kidney. The aim of
      this study was to estimate the long term renal function, survival and risk of
      recurrence of patients undergoing elective nephron sparing surgery for renal
      cancer on a solitary kidney. MATERIAL AND METHODS: Between January 1975 and
      December 2002, 37 elective nephron sparing surgery of kidney tumors were
      performed on 33 patients with a solitary kidney. Surgery was performed without
      interruption of blood flow. Pre- and postoperative renal function were compared
      by using a non parametric test of Kruskal and Wallis. Survival rates were
      estimated by the Kaplan Meier method and the prognostic factors were defined on a
      multivariate analysis using a Cox model. RESULTS: Mean tumoral diameter was 4.6
      cm [1.5-10]. The median follow-up was of 83 months. Three patients died in the
      postoperative period. The postoperative creatinine clairance was significantly
      lower than the preoperative value (p=0.01), but without significant variation of
      the renal dysfunction rate (p=0.18) and without significant decrease during the
      follow-up. No patient required chronic haemodialysis. Overall and disease-free
      survival rates at five and 10 years was 69 and 56.2%, and 55.8 and 27%,
      respectively. Multivariate analysis retained tumor size, Fuhrman grade and
      antecedent of controlateral cancer as independent prognostic factors in overall
      survival. CONCLUSION: In our experience, even in the presence of bad prognostic
      factors, nephron sparing surgery allows a relative savings of the long term renal
      function. Taking in account the poor life expectancy of people around 60 being
      put on haemodialysis, all attempt should be made to perform nephron sparing
      surgery in patients having a cancer on a solitary kidney.

PMID- 19168013
TI  - [Development of a pathological quality score of prostate biopsies].
AB  - OBJECTIVES: Develop a score allowing the pathologist to objectively report on the
      overall quality of extended standardized prostatic biopsy (EPB). METHODS: A
      prospective study was carried out on 339 consecutive protocols of 10 core EPB
      (PSA<10 ng/ml). Reports are standardized and computerized. The conclusion of the
      reports includes an estimate of the overall quality of the EPB based on three
      items to classify the protocols in three groups: protocol of "good" quality
      (group 1), "medium" quality (group 2) and "poor" quality (group 3). The score
      (IGap) is automatically computed from three objective criteria also shown on the
      conclusion of the report: the average length of the 10 biopsies (LM), the number
      of biopsies on which capsular elements can be identified (BCI) and the average
      number of fragment per biopsy (Fm). The IGap index rank from 0 to 1. The average
      IGap of the three groups is computed using the t-test. RESULTS: The average IGaps
      of the groups 1, 2 and 3 are respectively of 0,65 (0,37-0,89 ; n=250), 0,52 (0,36
      0,71 ; n=69) and 0,43 (0,22-0,6 ; n=20), (p<0,001). CONCLUSION: IGap is a
      pertinent score reporting objectively of the overall quality of EPB. An IGap
      close to one indicates a good quality of EPB. An IGap close to zero indicate a
      poor quality of EPB.

PMID- 19168014
TI  - [Epidemiology and histopronostic of prostatic cancer in Togo: about 202 cases
      diagnosed at the laboratory of pathology of the Tokoin teaching hospital of
      Lome].
AB  - OBJECTIVES: Describe the epidemiological and histological aspects of the prostate
      cancer in Togo. METHODS: It was a retrospective descriptive study relating to 202
      cases diagnosed between 1984 and 2003 at the Laboratory of Pathology of the
      Tokoin teaching hospital of Lome. The parameters studied were: frequency, age,
      circumstances of discovery, PSA value and histological type. RESULTS: The
      frequency of prostate cancer was 10 cases on average. The average age of patients
      was 70 years (45 to 95 years). The circumstances of discovery were dominated by
      voiding disorders and the average PSA was 88.5 ng/ml (7.8 to 560.4).
      Histologically, it was adenocarcinoma in 97.5% of cases and squamous cell
      carcinoma in 1.9% of cases. CONCLUSION: The prostate cancer although uncommon in
      Togo remains a public health problem because of the weak accessibility of the
      population to the diagnosis. So, a national program of screening is needed.

PMID- 19168015
TI  - [A technique of continent vesicostomy with ileocystoplasty: study of 32
      patients].
AB  - OBJECTIVES: To evaluate the functional outcomes and quality of life of adult's
      disabled motor with neurogenic bladders, who had undergone a continent
      catheterizable vesicostomy with ileocystoplasty permitting a systematic
      implantation of the stoma at the umbilicus without closure of the bladder neck.
      METHODS: Between 2004 and 2006, 32 adults with neurogenic bladder who underwent
      Mitrofanoff continent catheterizable vesicostomy with ileocystoplasty were
      evaluated with the "Qualiveen" and a local satisfaction questionnaire. The median
      age was 42.2 years. The neurological diagnoses were: spinal cord injury (26),
      spina bifida (two) and multiple sclerosis (four). The cystostomies were conducted
      with appendix (17) and the ileum according Monti's technique (15). The stomas
      were conducted in 29 cases at the umbilicus. RESULTS: The 31 patients were
      followed up for a mean of 21.6 months. The continence rate was 86%. The
      satisfaction with functional result and aesthetic of the stoma was of 88% and
      92%. Capacity to self catheterize increased from 64% to 88%. Thirty-three percent
      of stoma stenosis was noted and 36% of patients underwent a reintervention
      including 25% for stenosis. CONCLUSION: The results of this study have
      demonstrated that the ileocystoplasty with umbilical continent vesicostomy
      fullfill with treatment objective's of patients with neurogenic bladder:
      restoration of continence and improved quality of life by granting them social
      life.

PMID- 19168016
TI  - [Continent urinary derivation].

PMID- 19168017
TI  - [Assessment in a urological department of nurses' workload for neurological
      patients].
AB  - OBJECTIVES: To assess the nurses' workload in care of the neurological patients
      operated in a department of urology and compare it to the nurses' workload of
      oncological patients. METHOD: Between 2006 and 2007, a prospective study was
      realized in 15 consecutive patients with neurogenic voiding dysfunction managed
      by laparoscopic cystectomy and ileal conduit urinary diversion. The nurses'
      workload was assessed by the soins infirmiers individualises a la personne
      soignee (SIIPS) indicator. Three types of care were so estimated: basic care,
      technical care and relational care. Results were compared with the first 15
      patients in whom, during the same period, a laparoscopic cystectomy and ileal
      conduit urinary diversion was performed to treat a bladder cancer. RESULTS: The
      nurses' workload in basic care was higher for the neurological patient's compared
      to the oncological patients the day before the intervention and from the third
      postoperative day until the 8th postoperative day. The nurses' workload in
      relational care was higher in the neurological patient's the 2nd, 3rd, 6th and
      7th postoperative days. No difference was noted in terms of technical care
      between both groups. CONCLUSION: Except the operative day and the first
      postoperative day, the nurses' workload in relational and basic care is higher in
      the neurological patient's than in the oncological patients. No difference was
      noted in terms of technical care between both groups.

PMID- 19168018
TI  - [Use of double J ureteral stent as an alternative to prevent ureteroileal
      anastomosis stricture in orthotopic bladder substitution].
AB  - OBJECTIVE: The aim of the study was to compare ureteroileal anastomosis
      strictures rates in patients receiving either double J stent or open-ended
      ureteral stent, after bladder replacement for cancer. METHODS: Medical charts
      from 75 patients who underwent cystectomy and Z pouch bladder substitution for
      bladder cancer, between 2001 and 2005, were retrospectively reviewed.
      Ureteroileal anastomosis was direct, spatulated end-to-side fashioned in all
      patients. Double J stents were used in 39 patients (group A) and open-ended
      ureteral stent were used in 36 patients (group B). Mean hospital stay, early and
      late complications were also observed. RESULTS: Seventeen anastomotic strictures
      have been documented during the follow-up: 5.2% in group A versus 18.3% in group
      B (p=0.012). Mean catheterization period was six weeks in group A and 12 days in
      group B. No significant differences were found in mean hospital stay, early and
      late complications. CONCLUSION: The use of internal double J ureteral stent is
      now a feasible option and can decrease the rate of anastomotic stricture. The
      fact that the double J stent is removed after the anastomosis healing period may
      be a possible explanation.

PMID- 19168019
TI  - [Comparison of two sublingual types of desmopressin in 6-year-old and more
      children with primary nocturnal enuresis. About an international randomized cross
      over study].
AB  - OBJECTIVE: Desmopressin (a structural analogue of hormone arginine-vasopressine)
      is an effective treatment of primary nocturnal enuresis (PNE). A new oral
      formulation (oral lyophilisate; Minirinmelt has recently been developed. The
      principal objective of this study was to compare the preference of patients for
      the oral lyophilisate versus tablet. METHODS: This open-label, randomized, cross
      over study was undertaken at 26 centres across Europe and included patients with
      PNE. All were already receiving a stable dose of desmopressin tablets 0,2 or 0,4
      mg. Two hundred and fourteen patients aged 6 to 15 years were randomised (1:1) to
      receive the treatment in the order lyophilisate/tablet (n=108) or
      tablet/lyophilisate (n=106). Each formulation was taken during 3 weeks. RESULTS:
      Of the patients (intention to treat), 55,2% preferred the oral lyophilisate
      (p=0,16). Patients less than 12 years (n=153) had a preference for the
      lyophilisate compared to tablets (60,1%; p=0,015). Efficacy was the same for both
      formulations in terms of mean incidence of bedwetting episodes per week
      (treatment difference: -0,08; p=0,33). No serious adverse event was reported. The
      use was considered to be easy for the two forms (p=0,85). Of patients on the
      lyophilisate, 94,3% had compliance levels of greater or equal to 80%.
      CONCLUSIONS: The majority of patients preferred the sublingual lyophilisate. This
      preference was marked in patients less than 12 years on exploratory analysis. The
      new formulation of desmopressin requires no water intake and retains similar
      levels of efficacy and safety than the tablet.

PMID- 19168020
TI  - [Bladder metastasis of malignant melanoma: a case report and review of
      literature].
AB  - Metastatic malignant melanoma to the urinary bladder remains rare in clinical
      practice with less than 10 cases reported in the last 30 years in the literature.
      According to our knowledge, our case report is the first in french language.

PMID- 19168021
TI  - [Renal oncocytosis: case report].
AB  - Renal oncocytoma represent 5% of kidney tumors. Oncocytoma is a benign tumor,
      usually asymptomatic and fortuitous discovery. Standard treatment is tumorectomy
      when technically feasible. Surgery is indicated when oncocytoma becomes
      symptomatic, large or grows quickly. In a small proportion of cases, oncocytomas
      are bilateral and/or multifocal. These forms are most often sporadic or are
      integrated in the Birt-Hogg-Dube syndrome. We report here the case of a patient
      suffering from renal oncocytosis responsible for a diffuse renal involvement by
      numerous oncocytic nodules.

PMID- 19168022
TI  - [Bone-anchored suburethral sling complicated by pubic osteomyelitis: a case
      report].
AB  - The bulbo-urethral compression through a non-resorbable sling is a new
      therapeutic approach in the management of male stress urinary incontinence after
      prostatic surgery. Several slings are being evaluated and their way of fixing is
      variable according to the technique adopted. The InVancetrade mark process
      ensures bulbo-urethral compression by a synthetic sling anchored to the ischio
      pubic rami through several titanium screws. We report the case of two patients
      whose operating suites of the InVancetrade mark bone-anchored male sling surgery
      have been marked by the appearance of a perineal suppuration associated with a
      pubic osteomyelitis. The healing was achieved after explantation of the material
      implanted (screws and sling) with bone debridement and prolonged antibiotics.

PMID- 19168023
TI  - [Mycotic aneurysm and renal transplant. A case report].
AB  - The arterial aneurysm secondary to Candida is a rare but frightening complication
      of renal transplant. We report the case of a 58-year-old patient who developed an
      arterial aneurysm secondary to a Candida infection in 3 weeks of a third renal
      transplant. Candida albicans was isolated from the preservation solution. The
      treatment consisted of a transplant nephrectomy, aneurysm excision and an iliac
      bypass with cryopreserved iliac homograft. All of bacteriologic culture was
      positive for Candida. The positive bacteriologic culture for Candida in
      preservation solution requires antifongic treatment. In case of arterial
      aneurysm, a surgical treatment is necessary but majority of kidney transplant had
      to be removed.

PMID- 19168024
TI  - FitSpace explorer: an algorithm to evaluate multidimensional parameter space in
      fitting kinetic data.
AB  - Fitting several sets of kinetic data directly to a model based on numerical
      integration provides the best method to extract kinetic parameters without
      relying on the simplifying assumptions required to achieve analytical solutions
      of rate equations. However, modern computer programs make it too easy to enter an
      overly complex model, and standard error analysis grossly underestimates errors
      when a system is underconstrained and fails to reveal the full degree to which
      multiple parameters are linked through the complex relationships common in
      kinetic data. Here we describe the application of confidence contour analysis
      obtained by measuring the dependence of the sum square error on each pair of
      parameters while allowing all remaining parameters to be adjusted in seeking the
      best fit. The confidence contours reveal complex relationships between parameters
      and clearly outline the space over which parameters can vary (the "FitSpace").
      The utility of the method is illustrated by examples of well-constrained fits to
      published data on tryptophan synthase and the kinetics of oligonucleotide binding
      to a ribozyme. In contrast, analysis of alanine racemase clearly refutes claims
      that global analysis of progress curves can be used to extract the free energy
      profiles of enzyme-catalyzed reactions.

PMID- 19168025
TI  - Supramolecular organization of ATP synthase and respiratory chain in
      mitochondrial membranes.
AB  - Mitochondrial ATP synthase is mostly isolated in monomeric form, but in the inner
      mitochondrial membrane it seems to dimerize and to form higher oligomeric
      structures from dimeric building blocks. Following a period of electron
      microscopic single particle analyses that revealed an angular orientation of the
      membrane parts of monomeric ATP synthases in the dimeric structures, and after
      extensive studies of the monomer-monomer interface, the focus now shifts to the
      potentially dynamic state of the oligomeric structures, their potential
      involvement in metabolic regulation of mitochondria and cells, and to newly
      identified interactions like physical associations of complexes IV and V.
      Similarly, larger structures like respiratory strings that have been postulated
      to form from individual respiratory complexes and their supercomplexes, the
      respirasomes, come into the focus. Progress by structural investigations is
      paralleled by insights into the functional roles of respirasomes including
      substrate channelling and stabilization of individual complexes. Cardiolipin was
      found to be important for the structural stability of respirasomes which in turn
      is required to maintain cells and tissues in a healthy state. Defects in
      cardiolipin remodeling cause devastating diseases like Barth syndrome. Novel
      species-specific roles of respirasomes for the stability of respiratory complexes
      have been identified, and potential additional roles may be deduced from newly
      observed interactions of respirasomes with components of the protein import
      machinery and with the ADP/ATP translocator.

PMID- 19168026
TI  - The role of the mitochondrial permeability transition pore in heart disease.
AB  - Like Dr. Jeckyll and Mr. Hyde, mitochondria possess two distinct persona. Under
      normal physiological conditions they synthesise ATP to meet the energy needs of
      the beating heart. Here calcium acts as a signal to balance the rate of ATP
      production with ATP demand. However, when the heart is overloaded with calcium,
      especially when this is accompanied by oxidative stress, mitochondria embrace
      their darker side, and induce necrotic cell death of the myocytes. This happens
      acutely in reperfusion injury and chronically in congestive heart failure. Here
      calcium overload, adenine nucleotide depletion and oxidative stress combine
      forces to induce the opening of a non-specific pore in the mitochondrial
      membrane, known as the mitochondrial permeability transition pore (mPTP). The
      molecular nature of the mPTP remains controversial but current evidence
      implicates a matrix protein, cyclophilin-D (CyP-D) and two inner membrane
      proteins, the adenine nucleotide translocase (ANT) and the phosphate carrier
      (PiC). Inhibition of mPTP opening can be achieved with inhibitors of each
      component, but targeting CyP-D with cyclosporin A (CsA) and its non
      immunosuppressive analogues is the best described. In animal models, inhibition
      of mPTP opening by either CsA or genetic ablation of CyP-D provides strong
      protection from both reperfusion injury and congestive heart failure. This
      confirms the mPTP as a promising drug target in human cardiovascular disease.
      Indeed, the first clinical trials have shown CsA treatment improves recovery
      after treatment of a coronary thrombosis with angioplasty.

PMID- 19168027
TI  - Replacement of chlorophyll with di-vinyl chlorophyll in the antenna and reaction
      center complexes of the cyanobacterium Synechocystis sp. PCC 6803:
      characterization of spectral and photochemical properties.
AB  - Chlorophyll (Chl) a in a cyanobacterium Synechocystis sp. PCC 6803 was replaced
      with di-vinyl (DV)-Chl a by knock-out of the specific gene (slr1923), responsible
      for the reduction of a 8-vinyl group, and optical and photochemical properties of
      purified photosystem (PS) II complexes (DV-PS II) were investigated. We observed
      differences in the peak wavelengths of absorption and fluorescence spectra;
      however, replacement of Chl a with DV-Chl a had limited effects. On the contrary,
      photochemical reactions were highly sensitive to high-light treatments in the
      mutant. Specifically, DV-Chl a was rapidly bleached under high-light conditions,
      and we detected significant dissociation of complexes and degradation of D1
      proteins (PsbA). By comparing the SDS-PAGE patterns observed in this study to
      those observed in spinach chloroplasts, this degradation is assigned to the
      acceptor-side photoinhibition. The delayed fluorescence in the nanosecond time
      region at 77 K was suppressed in DV-PS II, possibly increasing triplet formation
      of Chl molecules. Our findings provide insight into the evolutionary processes of
      cyanobacteria. The effects of pigment replacement on the optimization of
      reactions are discussed.

PMID- 19168028
TI  - A novel lipid binding protein is a factor required for MgATP stimulation of the
      squid nerve Na+/Ca2+ exchanger.
AB  - Here we identify a cytosolic factor essential for MgATP up-regulation of the
      squid nerve Na(+)/Ca(2+) exchanger. Mass spectroscopy and Western blot analysis
      established that this factor is a member of the lipocalin super family of lipid
      binding proteins of 132 amino acids in length. We named it Regulatory protein of
      the squid nerve sodium calcium exchanger (ReP1-NCXSQ). ReP-1-NCXSQ was cloned,
      over expressed and purified. Far-UV circular dichroism and infrared spectra
      suggest a majority of beta-strand in the secondary structure. Moreover, the
      predicted tertiary structure indicates ten beta-sheets and two short alpha
      helices characteristic of most lipid binding proteins. Functional experiments
      showed that in order to be active ReP1-NCXSQ must become phosphorylated in the
      presence of MgATP by a kinase that is Staurosporin insensitive. Even more, the
      phosphorylated ReP1-NCXSQ is able to stimulate the exchanger in the absence of
      ATP. In addition to the identification of a new member of the lipid binding
      protein family, this work shows, for the first time, the requirement of a lipid
      binding protein for metabolic regulation of an ion transporting system.

PMID- 19168029
TI  - An insect farnesyl phosphatase homologous to the N-terminal domain of soluble
      epoxide hydrolase.
AB  - In insects, farnesyl pyrophosphate (FPP) is converted to juvenile hormone (JH)
      via a conserved pathway consisting of isoprenoid-derived metabolites. The first
      step of this pathway is presumed to be hydrolysis of FPP to farnesol in the ring
      gland. Based on alignment of putative phosphatases from Drosophila melanogaster
      with the phosphatase domain of soluble epoxide hydrolase, Phos2680 and Phos15739
      with conserved phosphatase motifs were identified, cloned and purified. Both D.
      melanogaster phosphatases hydrolyzed para-nitrophenyl phosphate, however,
      Phos15739 also hydrolyzed FPP with a K(cat)/K(m) of 2.1x10(5)M(-1)s(-1). RT-PCR
      analysis revealed that Phos15739 was expressed in the ring gland and its
      expression was correlated with JHIII titer during development of D. melanogaster.
      N-acetyl-S-geranylgeranyl-l-cysteine was found to be a potent inhibitor of
      Phos15739 with an IC(50) value of 4.4muM. Thus, our data identify Phos15739 as a
      FPP phosphatase that likely catalyzes the hydrolysis of FPP to farnesol in D.
      melanogaster.

PMID- 19168030
TI  - Expression of Aeromonas caviae ST pyruvate dehydrogenase complex components
      mediate tellurite resistance in Escherichia coli.
AB  - Potassium tellurite (K(2)TeO(3)) is harmful to most organisms and specific
      mechanisms explaining its toxicity are not well known to date. We previously
      reported that the lpdA gene product of the tellurite-resistant environmental
      isolate Aeromonas caviae ST is involved in the reduction of tellurite to
      elemental tellurium. In this work, we show that expression of A. caviae ST aceE,
      aceF, and lpdA genes, encoding pyruvate dehydrogenase, dihydrolipoamide
      transacetylase, and dihydrolipoamide dehydrogenase, respectively, results in
      tellurite resistance and decreased levels of tellurite-induced superoxide in
      Escherichia coli. In addition to oxidative damage resulting from tellurite
      exposure, a metabolic disorder would be simultaneously established in which the
      pyruvate dehydrogenase complex would represent an intracellular tellurite target.
      These results allow us to widen our vision regarding the molecular mechanisms
      involved in bacterial tellurite resistance by correlating tellurite toxicity and
      key enzymes of aerobic metabolism.

PMID- 19168031
TI  - A lipid binding domain in sphingosine kinase 2.
AB  - The lipid second messenger sphingosine 1-phosphate (S1P) is a critical mediator
      of cellular proliferation and survival signals, and is essential for
      vasculogenesis and neurogenesis. S1P formation is catalysed by sphingosine
      kinases 1 and 2 (Sphk1 and Sphk2). We have found that the endogenous glycolipid
      sulfatide (3-O-sulfogalactosylceramide) binds to and inhibits the activity of
      Sphk2 and the closely related ceramide kinase (Cerk), but not Sphk1. Using
      sulfatide as a probe, we mapped the lipid binding domain to the N-terminus of
      Sphk2 (residues 1-175), a region of sequence that is absent in Sphk1, but aligns
      with a pleckstrin homology domain in Cerk. Accordingly, Sphk2 bound to
      phosphatidylinositol monophosphates but not to abundant cellular phospholipids.
      Deleting the N-terminal domain reduced Sphk2 membrane localisation in cells. We
      have therefore identified a lipid binding domain in Sphk2 that is important for
      the enzyme's sub-cellular localisation.

PMID- 19168032
TI  - Potential role of chemerin in recruitment of plasmacytoid dendritic cells to
      diseased skin.
AB  - Interferon alpha-producing plasmacytoid dendritic cells (pDC) are crucial
      contributors to pro-inflammatory or tolerogenic immune responses and are
      important in autoimmune diseases such as psoriasis. pDC accumulate in the
      lesional skin of psoriasis patients, but are rarely found in the affected skin of
      patients with atopic dermatitis (AD). While homeostatic chemokine CXCL12 and
      inducible pro-inflammatory CXCR3 chemokine ligands may regulate pDC influx to
      psoriatic skin, the mechanism responsible for selective pDC recruitment in
      psoriasis vs. AD remains unknown. Circulating pDC from normal donors express a
      limited number of chemoattractant receptors, including CXCR3 and CMKLR1
      (chemokine-like receptor 1). In this work, we demonstrate that circulating pDC
      from normal donors as well as psoriasis and AD patients express similar levels of
      CXCR3 and responded similarly in functional migration assays to CXCL10. We next
      found that blood pDC from normal, AD, and psoriasis patients express functional
      CMKLR1. In contrast to normal skin, however, lesional skin from psoriasis
      patients contains the active form of the CMKLR1 ligand chemerin. Furthermore, in
      affected skin from psoriatic patients the level of active chemerin was generally
      higher than in AD skin. Taken together, these results indicate that local
      generation of active chemerin may contribute to pDC recruitment to psoriatic
      skin.

PMID- 19168033
TI  - Over-expression of C/EBP-alpha induces apoptosis in cultured rat hepatic stellate
      cells depending on p53 and peroxisome proliferator-activated receptor-gamma.
AB  - Hepatic stellate cells (HSCs) play a key role in the pathogenesis of hepatic
      fibrosis. In our previous studies, CCAAT enhancer binding protein-alpha (C/EBP
      alpha) has been shown to be involved in the activation of HSCs and to have a
      repression effect on hepatic fibrosis in vivo. However, the mechanisms are
      largely unknown. In this study, we show that the infection of adenovirus vector
      expressing C/EBP-alpha gene (Ad-C/EBP-alpha) could induce HSCs apoptosis in a
      dose- and time-dependent manner by Annexin V/PI staining, caspase-3 activation
      assay, and flow cytometry. Also, over-expression of C/EBP-alpha resulted in the
      up-regulation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      and P53, while P53 expression was regulated by PPAR-gamma. In addition, Fas,
      FasL, DR4, DR5, and TRAIL were studied. The results indicated that the death
      receptor pathway was mainly involved and regulated by PPAR-gamma and p53 in the
      process of apoptosis triggered by C/EBP-alpha in HSCs.

PMID- 19168034
TI  - Dissection of the inhibition of cardiac ryanodine receptors by human glutathione
      transferase GSTM2-2.
AB  - The muscle specific glutathione transferase GSTM2-2 inhibits the activity of
      cardiac ryanodine receptor (RyR2) calcium release channels with high affinity and
      activates skeletal RyR (RyR1) channels with lower affinity. To determine which
      overall region of the GSTM2-2 molecule supports binding to RyR2, we examined the
      effects of truncating GSTM2-2 on its ability to alter Ca(2+) release from
      sarcoplasmic reticulum (SR) vesicles and RyR channel activity. The C-terminal
      half of GSTM2-2 which lacks the critical GSH binding site supported the
      inhibition of RyR2, but did not support activation of RyR1. Smaller fragments of
      GSTM2-2 indicated that the C-terminal helix 6 was crucial for the action of GSTM2
      2 on RyR2. Only fragments containing the helix 6 sequence inhibited Ca(2+)
      release from cardiac SR. Single RyR2 channels were strongly inhibited by
      constructs containing the helix 6 sequence in combination with adjacent helices
      (helices 5-8 or 4-6). Fragments containing helices 5-6 or helix 6 sequences alone
      had less well-defined effects. Chemical cross-linking indicated that C-terminal
      helices 5-8 bound to RyR2, but not RyR1. Structural analysis with circular
      dichroism showed that the helical content was greater in the longer helix 6
      containing constructs, while the helix 6 sequence alone had minimal helical
      structure. Therefore the active centre of GSTM2-2 for inhibition of cardiac RyR2
      involves the helix 6 sequence and the helical nature of this region is essential
      for its efficacy. GSTM2-2 helices 5-8 may provide the basis for RyR2-specific
      compounds for experimental and therapeutic use.

PMID- 19168035
TI  - TRPC3 protein is expressed across the lifespan in human prefrontal cortex and
      cerebellum.
AB  - The canonical transient receptor potential type 3 (TRPC3) channel is a non
      selective, voltage-independent cation channel that is expressed in both excitable
      and non-excitable cells. As little is known regarding its presence in human brain
      and the influence of age on its expression, we examined TRPC3 protein expression
      by immunoblotting in postmortem prefrontal cortex and cerebellum obtained from
      subjects (8 days to 83 years) with no history of psychiatric or neurological
      disorder. The expression of TRPC3 protein in the prefrontal cortex (Brodmann area
      A9/A10) of the neonates/infants (<2 y) was significantly higher (25%) than that
      in the adolescent to adult (11y-83y) age group, whereas cerebellar TRPC3 levels
      showed no age-related changes. The results indicate that TRPC3 may be
      developmentally regulated in prefrontal cortex, and its expression in discrete
      human brain regions throughout the lifespan suggests a physiological role for
      TRPC3 during postnatal and adult life.

PMID- 19168036
TI  - Neutrophil elastase inhibitor attenuates hippocampal neuronal damage after
      transient forebrain ischemia in rats.
AB  - Inflammatory responses have been known to contribute to the development of
      neuronal damage after brain ischemia in experimental animals. Also, neutrophil
      elastase activity in the plasma has been elevated in the patients with acute
      cerebral infarction. In order to clarify whether neutrophil elastase distributes
      into the brain parenchyma and exacerbates neuronal damage following ischemia, we
      examined the effects of specific neutrophil elastase inhibitor, ONO-5046, on
      hippocampal CA1 neuronal death in relation to neutrophil elastase activity in the
      plasma and its distribution in the brain and to caspase-3/7 activity. ONO-5046 (5
      and 10 mg/kg) or saline (control group) was administrated after 8 min of
      forebrain ischemia in rats. Ratio of surviving neurons (median, [range]) in
      hippocampal CA1 seven days after ischemia was significantly higher in the ONO
      5046 5 mg/kg (31% [12-57%]), and 10 mg/kg groups (69% [39-76%]) than in the
      control group (3.2% [0-10%]). Plasma neutrophil elastase activity in the ONO-5046
      10 mg/kg group was significantly lower than in the control group (14 [11-25] vs.
      41 [35-68] nmol/ml). Neutrophil elastase distributed in the extracellular space
      in the hippocampal CA1 neuronal layer in the control group, while, in the ONO
      5046 10 mg/kg group, trace of neutrophil elastase was detected only in the
      endothelium. Caspase-3/7 activity was elevated after ischemia over 8 h in the
      control group, while, in the ONO-5046 10 mg/kg group, no elevation was observed.
      The results suggest that neutrophil elastase may contribute to neuronal death in
      hippocampal CA1 following forebrain ischemia and that neutrophil elastase
      inhibitor attenuates neuronal death.

PMID- 19168037
TI  - Estradiol increases Pet-1 and serotonin transporter mRNA in the midbrain raphe
      nuclei of ovariectomized rats.
AB  - Previous research has shown that estradiol increases the anorexia associated with
      serotonin (5-HT) neurotransmission. To examine further the putative relationship
      between estradiol and 5-HT, we investigated whether estradiol increases the
      expression of Pet-1 and the 5-HT transporter (5-HTT), two genes implicated in the
      development and regulation of the 5-HT system. Ovariectomized (OVX) rats (n=5
      6/group) were treated with 0, 2, or 10 microg estradiol benzoate (EB) in sesame
      oil on 2 consecutive days. Food intake and body weight were recorded 2 days later
      when EB-treated rats typically display signs of behavioral estrus (e.g., reduced
      feeding). Following the collection of behavioral data, rats were perfused, brains
      were removed, and coronal sections were cut through the midbrain raphe nuclei.
      Pet-1 and 5-HTT mRNA levels were quantified throughout the dorsal and median
      raphe nuclei (DRN and MRN) by conducting in situ hybridization on free-floating
      tissue sections using (35)S-labeled cDNA probes. As expected, EB treatment
      decreased food intake and body weight on the day that modeled estrus. At this
      same time, EB treatment increased Pet-1 and 5-HTT mRNA levels within the DRN and
      MRN. We conclude that a physiologically relevant regimen of estradiol treatment
      in OVX rats increases Pet-1 and 5-HTT mRNA levels in the midbrain raphe nuclei at
      a time when the anorexigenic effect of estradiol is apparent. Further studies are
      required to determine whether the increased expression of Pet-1 and 5-HTT mRNA
      plays a causal role in the anorexigenic effect of estradiol.

PMID- 19168038
TI  - Hydrogen gas is ineffective in moderate and severe neonatal hypoxia-ischemia rat
      models.
AB  - Hydrogen gas (H(2)) has been shown to ameliorate brain injury in experimental
      adult rat focal ischemia and in a mild neonatal hypoxia-ischemia (HI, 90 min
      hypoxia) rat model. In this study we tested H(2) in moderate (120 min hypoxia)
      and severe (150 min hypoxia) neonatal HI rat models. We hypothesized that H(2)
      would improve outcomes after neonatal HI by scavenging free radicals. Two hundred
      (200) unsexed Sprague-Dawley rats at day 10 of life (p10) underwent neonatal HI
      with the Rice-Vannucci model. Multiple treatment protocols were studied,
      including pre-ischemic treatment, intra-ischemic treatment, and post-ischemic
      treatment (Sham n=32, HI n=82, HI+H(2)n=86). We also tested H(2) in middle
      cerebral artery occlusion (MCAO) in adult rats (MCAO n=9, MCAO+H(2)n=7) for
      comparison. Analysis at 24 h included infarction volume, measurement of brain
      concentration of malondialdehyde (MDA) (an end-product of lipid peroxidation),
      daily weight, Nissl histology, and mortality. In moderate and severe neonatal HI
      models, hydrogen gas therapy (2.9% concentration H(2)) was not associated with
      decreased volume of infarction or decreased concentration of MDA. H(2) gas
      pretreatment (2.9%) was associated with increased infarction volume in neonatal
      HI. In MCAO in adult rats, H(2) gas therapy demonstrated a trend of beneficial
      effect. Exposure of H(2) gas to non-ischemic neonates resulted in a significant
      increase in brain concentration of MDA. We conclude that 2.9% H(2) gas therapy
      does not ameliorate moderate to severe ischemic damage in neonatal hypoxia
      ischemia.

PMID- 19168039
TI  - Cholesteryl ester transfer protein TaqIB, -629C>A and I405V polymorphisms and
      risk of coronary heart disease in an Indian population.
AB  - BACKGROUND: Polymorphisms in cholesteryl ester protein gene have been linked to
      risk of coronary heart disease (CHD) in many world populations through their
      effect on reverse cholesterol transport. METHODS: Five hundred four (504)
      unrelated electrocardiograph confirmed cases of CHD and 338 population based
      controls, matched by age and gender, belonging to the Tamilian population of
      south India were genotyped for polymorphisms in CETP gene using PCR RFLP methods.
      RESULTS: The multivariate logistic regression analyses demonstrated that CETP
      B1B1 and CA genotypes of TaqIB and -629C>A were significantly associated with
      increased risk for CHD (odds ratio (OR) 2.7; 95% confidence intervals (CI) (1.5
      3.3); OR 1.5 (1.1-2.4)) respectively. Combined wild genotypes of CETP gene showed
      an association with CHD (OR-1.7 (1.0-2.9) as well as the combined heterozygous
      mutants (OR 1.5 (1.0-2.3); p-0.03). Subgroup analysis based on gender revealed
      that men harboring CETP B1B1 and CA genotypes have a significant risk for CHD
      B1B1- 2.7 (1.7-4.3), CA-1.8 (1.3-2.6). There was no link between CETP I450V
      polymorphism and CHD. Analysis based on hypertensive status showed a significant
      association between these polymorphisms and non hypertensive CHD patients.
      CONCLUSIONS: The risk in non hypertensive and male CHD patients is higher in the
      presence of CETP B1B1 and CA genotypes.

PMID- 19168040
TI  - Comparison of performances of various HbA1c methods in Haemoglobin Camperdown
      variant detection: consequences in diabetes management.

PMID- 19168041
TI  - Assay-related issues in the measurement of cardiac troponins.
AB  - The recently released document by the Global Task Force on the universal
      definition of myocardial infarction (MI) has strengthened the role of cardiac
      troponin increase as the main criterion for MI diagnosis. Despite this pivotal
      role in clinical decisions, a number of assay-related issues can still markedly
      affect the test performance in the everyday practice. Regarding imprecision and
      analytical sensitivity, the performance of commercial assays is variable.
      Moreover, at least for troponin I, there is a lack of standardization among assay
      results. Appropriate cut points (99th percentile limit of the reference value
      distribution and/or 10% CV concentration value) can be established only if the
      assay performance is known and taken into account. Key characteristics to be
      defined include characterization by appropriate experimental and statistical
      protocols of the assay detection limit, total imprecision, and definition of the
      99th percentile limit of the reference population. The widespread introduction of
      cardiac troponin measurements is an undoubted improvement, but some performance
      differences still exist with commercial assays, which most clinicians are unaware
      of and may give rise to wrong marker interpretation.

PMID- 19168042
TI  - Sensitivity of thrombin-induced platelet aggregation to inhibition by ethanol.
AB  - BACKGROUND: The purpose of this study was to determine the concentration of
      ethanol required for inhibition of thrombin-induced aggregation of human
      platelets in vitro. METHODS: Three methods, light transmission method, particle
      counting method using light scattering and screen filtration pressure method
      using whole blood, were used for evaluation of platelet aggregation. RESULTS:
      Thrombin (0.2 U/ml)-induced platelet aggregation was significantly inhibited by
      ethanol, and the threshold ethanol concentrations for inhibition determined by
      measurements using the light transmission method, particle counting method and
      screen filtration pressure method were 0.5%, 0.125% and 2%, respectively.
      Platelet aggregation induced by a lower concentration (0.05 U/ml) of thrombin was
      detected by the screen filtration pressure method but not by the light
      transmission method or particle counting method. The threshold ethanol
      concentration for the inhibition of thrombin (0.05 U/ml)-induced platelet
      aggregation was 0.125% according to results obtained by using the screen
      filtration pressure method. CONCLUSIONS: Sensitivities for detection of thrombin
      induced platelet aggregation and for detection of inhibition of platelet
      aggregation by ethanol were high in the screen filtration pressure method and the
      particle counting method, respectively. The threshold concentration of ethanol to
      inhibit thrombin-induced platelet aggregation is about 0.125% (approximately 21
      mmol/l), which is easily attainable after drinking alcohol.

PMID- 19168043
TI  - Cuban neonatal screening of phenylketonuria using an ultramicro-fluorometric
      test.
AB  - BACKGROUND: Guthrie's bacterial inhibition assay was used in Cuba, since 1983. A
      decentralized program for the newborn screening of hyperphenylalaninemias started
      in the year 2000 using an ultramicro-fluorometric test (UMTEST PKU). METHODS: A
      simple and rapid ultramicro-fluorometric test based on McCaman and Robin's method
      has been designed, developed and applied for the measurement of Phe in dried
      blood spots on filter paper. RESULTS: The UMTEST PKU exhibited an acceptable
      precision and accuracy. Samples of 27528 newborns on filter paper Schleicher &
      Schuell 903 (S&S 903) from the National neonatal screening program were collected
      and analyzed, and the mean Phe concentration was 66.5 micromol/l. Our assay
      showed high Pearson and concordance correlations with 2 commercially available
      kits. A total of 521923 Cuban newborns were studied from the year 2000 to 2007
      using the UMTEST PKU. Elevated blood phenylalanine levels were found in 1764
      infants (0.34%) and no false negative were noted. Ten cases were diagnosed with
      phenylketonuria, all of them with an initial phenylalanine concentration over 360
      micromol/l. CONCLUSIONS: The analytical performance characteristics of our assay
      and its use in the National program have demonstrated its suitability for the
      neonatal screening of PKU.

PMID- 19168044
TI  - The clinical utility of parathyroid hormone-related peptide in the assessment of
      hypercalcemia.
AB  - BACKGROUND: Hypercalcemia is a common clinical finding with primary
      hyperparathyroidism and malignancy accounting for most cases. Measurement of
      parathyroid hormone-related peptide (PTHrP) is often requested for patients with
      hypercalcemia before confirmation of hypercalcemia and/or determination of
      parathyroid hormone (PTH) concentrations. We determined a PTH cutoff to guide
      PTHrP testing in hypercalcemic patients. METHODS: Test results for total calcium,
      intact PTH, and PTHrP tests performed within 2 days of each other were recorded.
      Chart review determined the etiology of hypercalcemia. The PTH cutoff below which
      a PTHrP result might be useful was determined. RESULTS: Test results from 123
      patients were included and 47 had hypercalcemia of malignancy, 15 of which had
      increased PTHrP. Diagnostic sensitivity and specificity were 32% (95% CI=19-47%)
      and 95% (95% CI=85-99%), respectively. PTH concentrations were lowest in patients
      with increased PTHrP compared to those with no increase (25.6+/-69.2 vs. 94.8+/
      332.8 ng/l, p<0.01). A cutoff PTH concentration of >26 ng/l predicted a non
      increased PTHrp result in 95% of the entire study population which increased to
      100% when only patients with hypercalcemia were considered. CONCLUSIONS: PTHrP
      testing is more appropriately performed after assessment of PTH. If the PTH is
      not low or low normal, testing for PTHrP is usually uninformative.

PMID- 19168045
TI  - Birth of mice from vitrified/warmed 2-cell embryos transported at a cold
      temperature.
AB  - Cryopreservation of 2-cell embryos is an effective technology for storage of
      genetically engineered mouse strains. Transport of genetically engineered mice
      between laboratories has frequently been performed using such cryopreserved 2
      cell embryos. However, the receiving laboratory requires proficient skills and
      special instruments to obtain live young from cryopreserved and transported
      embryos. Therefore, in this study, we tried to address the storage and transport
      of vitrified/warmed 2-cell embryos at a cold temperature. In cold storage
      experiments, the development rates of 2-cell embryos stored in M2 medium for 24,
      48 and 72 h into blastocysts were relatively high (83%, 63% and 43%,
      respectively). Although, 2-cell embryos stored in PB1 and mWM maintained the
      developmental potency for 24h, the rates were markedly decreased to low levels
      after 48 h (PB1: 0%; mWM: 5%). In transport experiments, many pups were obtained
      from vitrified/warmed 2-cell embryos transported at a cold temperature in all
      receiving laboratories (incidence of successful development: 49%; 249/511). In
      summary, short-term storage and transport of vitrified/warmed 2-cell embryos in
      M2 medium at a cold temperature can maintain their ability to develop into live
      young.

PMID- 19168046
TI  - G.B. Quan et al., Inhibition of high glucose-induced erythrocyte
      phosphatidylserine exposure by leupeptin and disaccharides, Cryobiology 56 (1)
      (2008) 53-61.

PMID- 19168047
TI  - Effects of analgesics on the plantar incision-induced drop of the noxious heat
      threshold measured with an increasing-temperature water bath in the rat.
AB  - The behavioural noxious heat threshold i.e. the lowest temperature evoking
      nocifensive behaviour was previously shown to decrease in short-lasting, but not
      in sustained, inflammatory thermal hyperalgesias. The aim of this study was to
      examine whether the surgical incision-induced lasting heat hyperalgesia involves
      a drop of the heat threshold and to assess the effects of conventional opioid and
      non-opioid analgesics in this model. One of the hind paws of rats was immersed
      into a water bath whose temperature was near-linearly increased from 30 degrees C
      until the animal withdrew its paw from the water. The corresponding bath
      temperature was considered as the behavioural noxious heat threshold.
      Hyperalgesia to heat was induced by a standardized plantar surgical incision
      performed under pentobarbital anaesthesia which led to a 5-7 degrees C decrease
      of the noxious heat threshold for seven days. Morphine, diclofenac, and
      paracetamol administered intraperitoneally 18 h after incision dose-dependently
      inhibited the drop of heat threshold with minimum effective doses of 0.3, 1, and
      100 mg/kg, respectively, as assessed 20, 30 and 40 min after treatment. Thermal
      hyperalgesia was also decreased by intraplantar treatment with morphine (10
      microg) or diclofenac (100 microg). In conclusion, the incision-induced sustained
      thermal hyperalgesia in rats involves a drop of the heat threshold suggesting
      that mechanisms of postsurgical pain are distinct from those of pure inflammatory
      pain. The thermal antihyperalgesic actions of systemically and/or locally applied
      morphine, diclofenac and paracetamol could be detected with high temporal
      resolution and sensitivity in this model.

PMID- 19168048
TI  - Dual action of AJG049, a novel gut selective Ca2+ channel antagonist, on Ba2+
      currents and contractions in guinea-pig antrum myocytes.
AB  - Ca(2+) channel antagonists are useful to reduce the abnormal motility in patients
      with irritable bowel syndrome. We have therefore examined the effects of a newly
      synthesized antagonist AJG049, on voltage-dependent L-type Ca(2+) channels in
      gastric antrum. Intracellular recordings were made from sheets of the circular
      muscle layer of guinea-pig gastric antrum, with simultaneous measurement of
      spontaneous contraction activity, and the effects of AJG049 were studied. The
      effects of AJG049 on voltage-dependent Ba(2+) currents (I(Ba)) and the basal
      membrane currents at -70 mV in dispersed smooth muscle cells were also
      investigated by the use of conventional whole-cell patch-clamp techniques.
      Although AJG049 (100 nM) enhanced the peak amplitude of spontaneous contractions,
      high concentrations (>or=10 microM) had inhibitory effects. In whole-cell
      configuration, AJG049 (10 nM) reversibly enhanced the peak amplitude of I(Ba) in
      a voltage-dependent manner whilst high concentrations (>or=100 nM) suppressed the
      peak amplitude in a concentration- and voltage-dependent manner. AJG049 (300 nM)
      caused little shift in the activation curve at a holding potential of -70 mV
      although the voltage dependence of the steady-state inactivation was shifted to
      more negative potentials by 5 mV in its presence. AJG049 caused a delay of the
      recovery from the inactivated state of I(Ba). Furthermore, AJG049 reduced the
      amplitude of the basal membrane currents at -70 mV in a concentration-dependent
      manner. These results suggest that AJG049 possesses a dual action on voltage
      dependent Ca(2+) channels in circular layer of guinea-pig antrum.

PMID- 19168049
TI  - Pharmacodynamic and pharmacokinetic interaction profiles of levetiracetam in
      combination with gabapentin, tiagabine and vigabatrin in the mouse
      pentylenetetrazole-induced seizure model: an isobolographic analysis.
AB  - To characterize the interactions between levetiracetam and the antiepileptic
      drugs gabapentin, tiagabine, and vigabatrin in suppressing pentylenetetrazole
      induced clonic seizures in mice, type II isobolographic analysis was used. Clonic
      seizures were evoked in Albino Swiss mice by subcutaneous injection of
      pentylenetetrazole at its CD(97)(98 mg/kg). Adverse-effect profiles with respect
      to motor performance, long-term memory and skeletal muscular strength were
      measured along with total brain antiepileptic drug concentrations. The
      combination of gabapentin with levetiracetam at the fixed-ratios of 2:1, 1:1,
      1:2, and 1:4 were supra-additive (synergistic) in terms of seizure suppression
      whilst the combination at the fixed-ratio of 4:1 was additive. Tiagabine with
      levetiracetam and vigabatrin with levetiracetam at the fixed-ratios of 1:25,
      1:50, 1:100, 1:200, and 1:400 and at 2:1, 3:1, 4:1, 6:1, 8:1, and 16:1 were
      additive, respectively. No acute adverse effects were observed. Measurement of
      total brain antiepileptic drug concentrations revealed that levetiracetam in
      combination with gabapentin at the fixed-ratio of 1:4 significantly elevated
      (21%) total brain gabapentin concentrations. In contrast, levetiracetam was
      without affect on tiagabine or vigabatrin concentrations and co-administration
      with gabapentin, tiagabine or vigabatrin had no effect on levetiracetam brain
      concentrations, indicating the pharmacodynamic nature of interaction between
      these antiepileptic drugs in the mouse pentylenetetrazole model. The combination
      of gabapentin with levetiracetam at the fixed-ratios of 2:1, 1:1, 1:2, and 1:4
      appears to be particularly favorable combination exerting supra-additive
      interaction in suppressing pentylenetetrazole-induced seizures, although there is
      a pharmacokinetic contribution to the interaction between levetiracetam and
      gabapentin at the fixed-ratio of 1:4. Levetiracetam in combination with tiagabine
      and vigabatrin appear to be neutral combinations producing only additivity in the
      mouse pentylenetetrazole model.

PMID- 19168050
TI  - Pharmacological properties of TD-6301, a novel bladder selective muscarinic
      receptor antagonist.
AB  - Existing antimuscarinic drugs for overactive bladder have high affinity for
      M(3)/M(1) muscarinic receptors and consequently produce M(3)/M(1)-mediated
      adverse effects including dry mouth, constipation, mydriasis and somnolence. TD
      6301 is a M(2/4) muscarinic receptor-selective antagonist developed for the
      treatment of overactive bladder. The present studies characterize the in vitro
      and in vivo pharmacological properties of this molecule in comparison to other
      marketed antimuscarinics agents. In radioligand binding studies, TD-6301 was
      found to possess high affinity for human M(2) muscarinic receptor (K(i)=0.36 nM)
      and was 31, 36, 2 and 128-fold selective for the human M(2) muscarinic receptor
      compared to the M(1), M(3), M(4) and M(5) muscarinic receptors, respectively. The
      in vivo bladder selectivity of TD-6301 in rats was determined to be 26, 28, >100,
      16 and 0.4-fold, respectively, assessed by comparing its potency for inhibition
      of volume-induced bladder contractions to that for inhibition of oxotremorine
      induced salivation, inhibition of small-intestinal transit, decreases in
      locomotor activity, increases in pupil diameter and increases in heart rate. TD
      6301 was more potent in inhibiting volume-induced bladder contractions
      (ID(50)=0.075 mg/kg) compared to oxotremorine-induced salivation (ID(50)=1.0
      mg/kg) resulting in a bladder/salivary gland selectivity ratio greater than that
      observed for tolterodine, oxybutynin, darifenacin and solifenacin. The
      preclinical properties of TD-6301 suggest that this molecule is likely to be
      efficacious in overactive bladder patients with a lower propensity to cause M(3)
      muscarinic receptor mediated adverse effects.

PMID- 19168051
TI  - Pharmacological assessment of the rat formalin test utilizing the clinically used
      analgesic drugs gabapentin, lamotrigine, morphine, duloxetine, tramadol and
      ibuprofen: influence of low and high formalin concentrations.
AB  - The formalin test is used as a primary behavioural screen for assaying the
      antinociceptive activity of compounds in laboratory rodents. After hindpaw
      formalin injection, nociceptive behaviours are expressed in a biphasic pattern
      and correlate closely with the concentration of formalin injected. Here, the
      antinociceptive efficacy of six compounds used in the clinical treatment of
      chronic pain was compared in rats injected with either 1% or 5% formalin.
      Predictably, the anti-inflammatory drug ibuprofen (30-300 mg/kg) attenuated
      second phase (16-40 min) nociceptive behaviours in 5% formalin-injected rats; 1%
      formalin-injected rats were unaffected. The anti-epileptic drugs gabapentin (50
      200 mg/kg) and lamotrigine (10-60 mg/kg) were antinociceptive only during second
      phase in both 1% and 5% tests. Notably, they were 2-4 times more potent in 1% vs
      5% formalin-injected rats. The dual monoamine reuptake inhibitor duloxetine (3-60
      mg/kg) consistently attenuated nociceptive behaviours during first phase and
      interphase in both tests. However second phase nociception was only attenuated in
      5% formalin-injected rats giving rise to a 6 fold increase in potency compared
      with 1% formalin-injected rats. The micro-opioid receptor agonist morphine (1-6
      mg/kg) and the combined micro-opioid receptor agonist/monoamine reuptake
      inhibitor tramadol (5-50 mg/kg) both attenuated nociceptive behaviours throughout
      the duration of both the 1% and 5% tests; no difference in antinociceptive
      potency occurred for either compound during second phase. Thus, for
      mechanistically-distinct compounds the predictive antinociceptive capacity of the
      formalin test can vary with the concentration of formalin injected, likely as a
      result of peripheral and central nociceptive signalling mechanisms being
      differentially engaged.

PMID- 19168052
TI  - Chronic 13-cis-retinoic acid administration disrupts network interactions between
      the raphe nuclei and the hippocampal system in young adult mice.
AB  - Previously, we showed that chronic administration of 13-cis-retinoic acid (13-cis
      RA) induces depression-related behaviors in mice and that 13-cis-RA alters
      components of the serotonergic system in vitro. Work by others has shown that 13
      cis-RA reduces hippocampal neurogenesis in mice and orbitofrontal cortex
      metabolism in humans. In the current study, we measured cytochrome oxidase
      activity, a metabolic marker that reflects steady state neuronal energy demand,
      in various regions of the brain to determine the effects of 13-cis-RA on neuronal
      metabolic activity and network interactions between the raphe nuclei and the
      hippocampal system. Brain cytochrome oxidase activity in young adult male mice
      was analyzed following 6 weeks of daily 13-cis-RA (1 mg/kg) or vehicle injection
      and behavioral testing. Chronic 13-cis-RA administration significantly decreased
      cytochrome oxidase activity only in the inferior rostral linear nucleus of the
      raphe. However, covariance analysis of interregional correlations in cytochrome
      oxidase activity revealed that 13-cis-RA treatment caused a functional uncoupling
      between the dorsal raphe nuclei and the hippocampus. Furthermore, a path analysis
      indicated that a network comprising lateral habenula to dorsal raphe to
      hippocampus was effectively uncoupled in 13-cis-RA treated animals. Finally,
      cytochrome oxidase activity in the dentate gyrus of 13-cis-RA treated mice was
      inversely correlated with depression-related behavior. Taken together, these data
      show that 13-cis-RA alters raphe metabolism and disrupts functional connectivity
      between the raphe nuclei and the hippocampal formation, which may contribute to
      the observed increase in depression-related behaviors.

PMID- 19168053
TI  - Antinociceptive activity of buprenorphine and lumiracoxib in the rat orofacial
      formalin test: a combination analysis study.
AB  - Combination of two or more analgesics is widely used for the treatment of
      moderate and severe pain syndromes, allowing usage of lower doses of each
      compound and thereby limiting side effects; there is currently a large interest
      in investigating the potential advantages of combinations between opioids and non
      steroidal inflammatory drugs (NSAIDs), coxibs in particular. The rat orofacial
      formalin test is a useful pre-clinical model of inflammatory trigeminal pain for
      evaluating antinociceptive activity of analgesics and their combinations.
      Injection of formalin in the rat wiskerpad induces a stereotyped response
      (rubbing), consisting of two distinct phases: a first 'phasic' phase and a second
      'tonic' phase. In this work we tested a partial agonist to mu-opioid receptors,
      buprenorphine, and a selective cyclo-oxygenase-2 inhibitor, lumiracoxib, each of
      which given i.p. either alone or in combination. Buprenorphine reduced
      nociception both in the first and in the second phase, whereas lumiracoxib
      induced antinociception in the second phase only. The interaction between the two
      drugs was assessed through isobolographic analysis after combined administration
      at a fixed dose ratio. Such combination produced a dose-dependent antinociceptive
      effect in both phases. We observed a statistical difference between the
      theoretical and the experimental ED(50), which indicated synergistic interaction
      in the second phase. Concerning the first phase, we assumed that the
      antinociceptive effects were almost completely to be attributed to buprenorphine,
      since lumiracoxib was ineffective when administered alone. However, we found an
      unexpected difference between the theoretical and experimental ED(50), suggesting
      synergism in the first phase as well.

PMID- 19168055
TI  - Azelnidipine inhibits aldosterone synthesis and secretion in human adrenocortical
      cell line NCI-H295R.
AB  - Blockade of a mineralocorticoid receptor is a clinically useful approach to the
      prevention of cardiovascular disease. The present study was designed to evaluate
      the effect of azelnidipine, a unique dihydropyridine Ca(2+) channel blocker, on
      aldosterone production in the human adrenocortical cell line NCI-H295R.
      Azelnidipine inhibited angiotensin II- and KCl-induced expression of steroid
      11beta-hydroxylase, steroid 18-hydroxylase, and the alpha1H subunit of the T-type
      Ca(2+) channel, and suppressed steroid biosynthesis in H295R cells by the same
      amount as efonidipine. On the basis of these findings, azelnidipine appears to
      suppress steroid biosynthesis in H295R cells beyond the blockade of L-type
      calcium channels.

PMID- 19168054
TI  - Varenicline has antidepressant-like activity in the forced swim test and augments
      sertraline's effect.
AB  - Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist
      developed as a smoking cessation aid, showed antidepressant-like activity in the
      forced swim test in two mouse strains. In addition, a low varenicline dose
      significantly enhanced the effects of moderately active doses of the selective
      serotonin reuptake inhibitor sertraline. These findings are consistent with the
      notion that reducing alpha4beta2 nicotinic acetylcholine receptor activity either
      by antagonists or by partial agonists that can partially activate or desensitize
      acetylcholine receptors is associated with antidepressant-like properties. These
      data suggest that varenicline may have antidepressant potential and can, when
      combined, augment antidepressant responses of selective serotonin reuptake
      inhibitors.

PMID- 19168056
TI  - Pharmacological comparison of muscarinic ligands: historical versus more recent
      muscarinic M1-preferring receptor agonists.
AB  - In functional assay assessments using the five muscarinic receptor subtypes, a
      second generation of muscarinic M(1)-preferring receptor agonists [AC-42 (1), AC
      260584 (2), 77-LH-28-1 (3) and LY-593039 (4)] was shown to have higher
      selectivity for muscarinic M(1) over M(3) receptor as compared to historical
      agonists [talsaclidine (8), sabcomeline (10), xanomeline (11), WAY-132983 (12),
      cevimeline (9) and NGX-267 (6)]. Another striking difference of these more recent
      compounds is their affinities for the dopamine D(2) and 5-HT(2B) receptors. Taken
      together, these results suggest that the newer compounds may have a greater
      clinical safety profile, especially with regard to muscarinic M(3) receptor
      mediated events, than the historical agonists, but their affinities for other
      receptors may still compromise their use to validate the therapeutic potential of
      muscarinic M(1) receptor agonists.

PMID- 19168057
TI  - In vivo antagonism of the behavioral responses to L-3-,4-dihydroxyphenylalanine
      by L-3-,4-dihydroxyphenylalanine cyclohexyl ester in conscious rats.
AB  - To establish the neurotransmitter role(s) of L-3,4-dihydroxyphenylalanine (DOPA)
      in its own right, we attempted to clarify whether i.p. injection of a DOPA
      antagonist, DOPA cyclohexyl ester (CHE), would antagonize the behavioral
      responses of conscious rats to DOPA in the presence of 3-hydroxybenzylhydrazine
      (NSD-1015) (100 mg/kg i.p.), a central aromatic L-amino acid decarboxylase (AADC)
      inhibitor. DOPA-CHE (40, 60 and 100 mg/kg) elicited a dose-dependent partial
      antagonism against the increase in locomotor activity induced by DOPA (100 mg/kg
      i.p.). A low dose of DOPA-CHE (10 mg/kg) elicited full antagonism against the
      potentiating effect of a non-effective dose of DOPA (20 mg/kg) on the increase in
      locomotor activity induced by a dopamine D(2) agonist quinpirole (0.3 mg/kg
      s.c.). DOPA-CHE (100 mg/kg) elicited full antagonism against licking behavior
      induced by DOPA (100 mg/kg). We confirmed that DOPA (100 mg/kg) increased the
      striatal dopamine content but elicited no effect on locomotor activity in the
      presence of benserazide (50 mg/kg i.p.), a peripheral AADC inhibitor. DOPA also
      increased the dopamine content in the presence of NSD-1015 to a maximal degree
      similar to that in the presence of benserazide. Thus, we conclude that DOPA-CHE
      is a suitable DOPA antagonist that would be available under in vivo experimental
      conditions. DOPA plays a role in the neuromodulation of behavior.

PMID- 19168058
TI  - Heme-oxygenase induction inhibits arteriolar thrombosis in vivo: effect of the
      non-substrate inducer cobalt protoporphyrin.
AB  - Heme oxygenase-1 (HO) metabolizes heme to form the vasodilator carbon monoxide
      and antioxidant biliverdin. Upregulation of HO-1 by hemin, which is also a
      substrate attenuates thrombosis in rodent models, however, whether protection is
      due to HO-1 upregulation or to increased substrate availability is unknown. This
      study tested the hypothesis that treatment of mice with cobalt protoporphyrin
      (CoPP), a non-substrate HO-1 inducer, would protect the endothelium from laser
      injury. C57Bl/J6 mice were treated with vehicle, CoPP (20 mg/kg), CoPP plus the
      HO-1 inhibitor tin protoporphyrin (SnPP; 20 mg/kg) or SnPP alone for 18 h.
      Intravital microscopy was used to quantitate thrombus formation in cremaster
      arterioles in response to laser ablation of the endothelium. CoPP treatment
      inhibited thrombosis by 43% compared to vehicle (P<0.05). SnPP co-treatment
      negated the inhibitory effect of CoPP while SnPP alone potentiated thrombosis
      compared to vehicle. In CoPP-treated animals, cremaster HO-1 mRNA expression was
      increased 59+/-17-fold over vehicle (P<0.001). Co-treatment with CoPP+SnPP
      attenuated this effect by 36%, however the increase in HO-1 protein induced by
      CoPP was unaffected by SnPP. Induction of HO-1 by the non-substrate inducer CoPP
      protects against laser induced endothelial injury without the need for increased
      substrate. Small molecule, substrate-independent upregulation of HO-1 expression
      represents a feasible approach to ameliorate endothelial dysfunction in
      cardiovascular disease.

PMID- 19168059
TI  - The effect of the neuroactive steroid 5beta-pregnane-3beta, 20(R)-diol on the
      time course of GABA evoked currents is different to that of pregnenolone
      sulphate.
AB  - The endogenous progesterone metabolite allopregnanolone has a number of
      properties including anesthetic, sedative, antiepileptic, anxiolytic, impaired
      memory function and negative mood symptoms. Allopregnanolone is a potent positive
      GABA(A) receptor function modulators. In contrast, 3beta-hydroxy-steroids (3beta
      steroids) usually modulate the GABA(A) receptor negatively. They have attracted
      some interest for their possible use as therapeutic agents that could counteract
      the negative symptoms induced by allopregnanolone. Two hypotheses for the action
      of 3beta-steroids have been proposed: 1) 3beta-steroids act in a similar way to
      pregnenolone sulphate, which non-competitively reduces GABA(A) receptor activity.
      2) 3beta-steroids specifically antagonize the effect of allopregnanolone. We have
      therefore tried to clarify this issue by comparing the effect of pregnenolone
      sulphate and 5beta-pregnane-3beta, 20(R)-diol on the GABA-evoked currents by the
      patch clamp technique on neurons from the medial preoptic nucleus. Both
      pregnenolone sulphate and 5beta-pregnane-3beta, 20(R)-diol increase the
      desensitization rate of the current response evoked by a 2 s GABA application.
      However, their effects on other parameters of the GABA evoked currents differed
      in degree and sometimes even in direction. The actions of pregnenolone sulphate
      and 5beta-pregnane-3beta, 20(R)-diol were not altered in the presence of
      allopregnanolone, which indicates that they do not directly interact with
      allopregnanolone. In addition, when 5beta-pregnane-3beta, 20(R)-diol was tested
      on spontaneous inhibitory postsynaptic currents (sIPSCs), it dramatically reduced
      the allopregnanolone-induced prolongation of the decay time constant but it had
      no effect on the decay under control conditions. In conclusion, the effect of
      5beta-pregnane-3beta, 20(R)-diol on GABA-evoked currents is different to that of
      pregnenolone sulphate in medial preoptic nucleus neurons.

PMID- 19168060
TI  - Migration potential and gene expression profile of human mesenchymal stem cells
      induced by CCL25.
AB  - Recruitment of mesenchymal stem cells (MSC) to tissue damages is a promising
      approach for in situ tissue regeneration. The physiological mechanisms and
      regulatory processes of MSC trafficking to injured tissue remain poorly
      understood. However, the pivotal role of chemokines in MSC recruitment has
      already been shown. The aim of this study was to determine the migratory
      potential and the gene expression profile of MSC stimulated with the CC chemokine
      CCL25 (TECK). Bone marrow derived human MSC were exposed to different doses of
      CCL25 in a standardized chemotaxis assay. Microarray gene expression profiling
      and pathway analysis were performed for CCL25 stimulated MSC. Maximum migration
      of MSC towards CCL25 was observed at 10(3) nM. Microarray analysis revealed an
      induction of molecules directly involved in chemotaxis and homing of bone marrow
      cells (CXCL1-3, CXCL8, PDE4B), cytoskeletal and membrane reorganisation (CXCL8,
      PLD1, IGFBP1), cellular polarity (PLD1), and cell movement (CXCL1-3, CXCL6,
      CXCL8, PTGS2, PDE4B, TGM2). Respective chemokine secretion was confirmed by
      protein membrane-array analysis. The activation of CXCR2 ligands (CXCL1-3, CXCL5
      6, CXCL8) and a LIF-receptor/gp130 ligand (LIF) indicated an involvement of the
      respective signaling pathways during initiation of chemotaxis and migration.
      These results suggest CCL25 as a new potential candidate for further in situ
      regeneration approaches.

PMID- 19168061
TI  - Environmental enrichment promotes fiber sprouting after deafferentation of the
      superior colliculus in the adult rat brain.
AB  - Exposure to an enriched environment has proven to be beneficial in the recovery
      of function after brain lesions, but the underlying mechanisms remain only partly
      understood. One possibility is that environmental enrichment stimulates the
      reorganization of areas and fiber tracts that have been spared by the injury.
      Here we evaluate the effects of enriched environment on the sprouting of
      undamaged retinal afferents into the deafferented superior colliculus (SC) after
      a partial retinal lesion in adult rats. Anterograde tracing of retinal axons
      demonstrated a significant increase in fiber sprouting in the denervated SC of
      animals reared in enriched environment compared to animals reared in standard
      conditions. Environmental enrichment also promoted a substantial recovery of
      synaptic sites within the deafferented SC as shown by both synapsin I and
      vesicular glutamate transporter 2 immunostaining. These data provide evidence
      that environmental enrichment stimulates axonal plasticity and synaptic
      reorganization following brain injury.

PMID- 19168062
TI  - Theta activity of septal neurons during different epileptic phases: the same
      frequency but different significance?
AB  - The multiunit activity in the medial septal-diagonal band complex (MSDB) and
      field potentials of the hippocampus were simultaneously recorded in waking
      healthy rabbits (control) and in the same animals that were then exposed to
      kindling stimulation of the perforant path. In the control, the bursts of spikes
      in one group of rhythmic MSDB neurons phase-locked to the top of theta waves in
      the hippocampus, and in the second group, to the trough of these waves. The
      stimulation evoked seizure afterdischarges in the hippocampus and seizure bursts
      of spikes separated by periods of inhibition in MSDB neurons. In the first group
      of septal cells, seizure bursts coincided with inhibitory periods between
      afterdischarges in the hippocampus; in the second group, these bursts were
      observed during seizure afterdischarges, suggesting that different MSDB cells
      play opposite roles in the development of seizures. Evoked afterdischarges were
      spontaneously followed by recurrent ictal events; neuronal oscillations at the
      theta (6-7 Hz) or "twice-theta" frequency (12-14 Hz) preceded these secondary
      epileptic discharges. As a result of kindling, interictal spikes were recorded in
      the hippocampus; at the same time, synchronous bursts of many cells appeared in
      the MSDB. In the epileptic brain, the frequency of both the hippocampal theta
      rhythm and MSDB neuronal theta bursts increased; in the septum, an augmentation
      of neuronal rhythmicity was also observed. Theta oscillations, either spontaneous
      or evoked by sensory stimulation, abolished the epileptiform events. Evidently,
      the activities within the theta range during preictal and interictal periods are
      of different significance in the generation of seizures.

PMID- 19168064
TI  - Pancreatic imaging: current state of the art.

PMID- 19168065
TI  - MicroRNAs make inroads into liver development.

PMID- 19168067
TI  - The promise and challenges of biobanking in digestive disease research.

PMID- 19168068
TI  - Searching for generality in the patterns of parasite abundance and distribution:
      ectoparasites of a South African rodent, Rhabdomys pumilio.
AB  - We studied abundance and distribution of seven ectoparasite species (fleas
      Chiastopsylla rossi and Dynopsyllus ellobius, a louse Polyplax arvicanthis, mites
      Androlaelaps fahrenholzi and Laelaps giganteus and two ticks Haemaphysalis
      elliptica and Hyalomma truncatum) exploiting the same populations of the rodent
      host Rhabdomys pumilio in South Africa. We considered three general patterns of
      abundance and distribution, namely (i) aggregated distribution of parasites
      amongst individual hosts; (ii) positive relationships between mean parasite
      abundance and their prevalence; and (iii) applicability of a simple
      epidemiological model based on mean parasite abundance and its variance to
      predict the observed patterns of prevalence. Our aims were to evaluate the
      relative role of host- versus parasite-associated factors by looking at
      similarity amongst different parasites in these patterns. In general, all
      parasites demonstrated strong similarity in each of the three patterns of
      abundance and distribution. However, the strength of these patterns differed
      amongst parasite species. We conclude that these patterns are driven mainly by
      hosts, but differences are caused by differences between various life-history
      traits of parasite species. Our results support the idea that general laws apply
      to parasite population ecology.

PMID- 19168069
TI  - Time profiles of the expression of metalloproteinases, tissue inhibitors of
      metalloproteases, cytokines and collagens in hamsters infected with Opisthorchis
      viverrini with special reference to peribiliary fibrosis and liver injury.
AB  - The liver fluke Opisthorchis viverrini is endemic in southeastern Asia, and
      causes cholangiocarcinoma and liver fibrosis. We investigated the time profile of
      the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs
      (TIMPs) in relation to peribiliary fibrosis in O. viverrini-infected hamsters.
      Hepatic mRNA expression of MMPs, TIMPs, cytokines and collagens I and III was
      assessed by quantitative reverse transcription-PCR. Zymography and
      immunohistochemistry were also used to examine MMPs-2 and -9 expression. After
      infection, an increase of peribiliary fibrosis was time-dependent. Opisthorhis
      viverrini-induced gene expression in hamster liver, with increased mRNA
      expression levels of IL-1beta, TNF-alpha, TGF-beta, and collagens I and III, was
      observed at 21 days p.i. Expression of MMPs-2, -13 and -14 and TIMPs-1 and -3
      genes, was significantly higher at 1 month, and maximal levels of most MMPs (MMPs
      2, -9, -13 and -14) were observed at 2 months p.i. The cytoplasmic levels of MMP
      2 and MMP-9 were similar to mRNA expression. Immunohistochemistry revealed that
      MMP-9 was expressed mainly in the cytoplasm of inflammatory cells at the invasive
      front of the fibrous area. In contrast, the highest levels of mRNA expression of
      TIMPs-2 and -3, and TGF-beta were observed 10 months p.i. Concentration of TIMP-2
      protein in the plasma correlated with its transcriptional level (r=0.320,
      P=0.040). Peribiliary fibrosis correlated positively with liver hydroxyproline
      content (r=0.846, P<0.001), plasma hydroxyproline concentration (r=0.770,
      P<0.001), plasma TIMP-2 level (r=0.335, P=0.046), and mRNA expression levels of
      MMP-7 (r=0.511, P=0.006), TIMP-1 (r=0.320, P=0.040), TIMP-2 (r=0.428, P=0.026),
      and TIMP-3 (r=0.553, P=0.003). This study suggests that expression of MMPs is
      associated with an inflammatory reaction in the early phase and TIMPs expression
      at the late phase may contribute to both fibrosis and liver injury. MMPs and
      TIMPs may serve as diagnostic markers for the severity of O. viverrini-induced
      liver injury.

PMID- 19168070
TI  - Human connexin31.9, unlike its orthologous protein connexin30.2 in the mouse, is
      not detectable in the human cardiac conduction system.
AB  - In the human heart connexin(Cx)40, Cx43 and Cx45-containing gap junctional
      channels electrically couple cardiomyocytes, forming a functional syncytium. In
      the mouse heart, additionally, Cx30.2-containing gap junctions have been detected
      in the atrioventricular node where they are implicated, together with Cx45, in
      impulse delay. However, whether the human ortholog of Cx30.2, Cx31.9, is
      expressed in the human heart has not previously been investigated. We therefore
      generated Cx31.9 specific antibodies to test for the expression of Cx31.9 in the
      human heart. These antibodies recognized the Cx31.9 protein in HeLaCx31.9
      transfectants by immunofluorescence and immunoblot analyses. However, we did not
      find punctate Cx31.9 specific immunofluorescence signals in the working
      myocardium or in the impulse generation and conduction system of adult or fetal
      human heart. Complementary immunoblot analyses did not reveal Cx31.9 protein in
      the adult atrial or ventricular myocardium. We conclude that the Cx31.9 protein,
      unlike its counterpart in the mouse, is not expressed in detectable quantities
      and is thus unlikely to contribute to the impulse generation and conduction
      system or the working myocardium of the human heart.

PMID- 19168071
TI  - PERIOD2 is a circadian negative regulator of PAI-1 gene expression in mice.
AB  - An increased level of obesity-induced plasma plasminogen activator inhibitor-1
      (PAI-1) is considered a risk factor for cardiovascular disease. To determine
      whether the circadian clock component PERIOD2 (PER2) is involved in the
      regulation of PAI-1 gene expression, we performed transient transfection assays
      in vitro, and generated transgenic (Tg) mice overexpressing PER2. We then
      compared PAI-1 expression in Tg and wild-type (WT) mice with or without obesity
      induced by a high-fat/high-sucrose diet. PER2 suppressed CLOCK:BMAL1- and
      CLOCK:BMAL2-dependent transactivation of the PAI-1 promoter in vitro.
      Furthermore, nuclear translocation is dispensable for PER2 to suppress
      CLOCK:BMAL1-dependent transactivation of the PAI-1 promoter, because functional
      loss of the nuclear localization domain did not affect either the interaction
      with BMAL1 or the suppressive role of PER2. The diurnal expression of clock and
      clock-controlled genes was disrupted in a gene-specific manner, whereas that of
      PAI-1 mRNA was significantly damped in the hearts of PER2 Tg mice fed with a
      normal diet. Obesity-induced plasma PAI-1 increase was significantly suppressed
      in Tg mice in accordance with cardiac PAI-1 mRNA levels, whereas body weight gain
      and changes in metabolic parameters were identical between WT and Tg mice.
      Endogenous PAI-1 gene expression induced by transforming growth factor-beta1 was
      significantly attenuated in embryonic fibroblasts derived from Tg mice compared
      with those from WT mice. Our results demonstrated that PER2 represses PAI-1 gene
      transcription in a BMAL1/2-dependent manner. The present findings also suggest
      that PER2 attenuates obesity-induced hypofibrinolysis by downregulating PAI-1
      expression independently of metabolic disorders.

PMID- 19168072
TI  - Fas apoptosis inhibitory molecule contains a novel beta-sandwich in contact with
      a partially ordered domain.
AB  - Fas apoptosis inhibitory molecule (FAIM) is a soluble cytosolic protein inhibitor
      of programmed cell death and is found in organisms throughout the animal kingdom.
      A short isoform of FAIM is expressed in all tissue types, while an alternatively
      spliced long isoform is specifically expressed in the brain. Here, the short
      isoform is shown to consist of two independently folding domains in contact with
      each other. The NMR solution structure of the C-terminal domain of murine FAIM is
      solved in isolation and revealed to be a novel protein fold, a noninterleaved
      seven-stranded beta-sandwich. The structure and sequence reveal several residues
      that are likely to be involved in functionally significant interactions with the
      N-terminal domain or other binding partners. Chemical shift perturbation is used
      to elucidate contacts made between the N-terminal domain and the C-terminal
      domain.

PMID- 19168073
TI  - Markov chain Monte Carlo fitting of single-channel data from inositol
      trisphosphate receptors.
AB  - In many cell types, the inositol trisphosphate receptor (IPR) is one of the
      important components that control intracellular calcium dynamics, and an
      understanding of this receptor (which is also a calcium channel) is necessary for
      an understanding of calcium oscillations and waves. Recent advances in
      experimental techniques now allow for the measurement of single-channel activity
      of the IPR in conditions similar to its native environment, and these data can be
      used to determine the rate constants in Markov models of the IPR. We illustrate a
      parameter estimation method based on Markov chain Monte Carlo, which can be used
      to fit directly to single-channel data, and determining, as an intrinsic part of
      the fit, the times at which the IPR is opening and closing. We show, using
      simulated data, the most complex Markov model that can be unambiguously
      determined from steady-state data and show that non-steady-state data is required
      to determine more complex models.

PMID- 19168074
TI  - Mean-field modeling of the basal ganglia-thalamocortical system. I Firing rates
      in healthy and parkinsonian states.
AB  - Parkinsonism leads to various electrophysiological changes in the basal ganglia
      thalamocortical system (BGTCS), often including elevated discharge rates of the
      subthalamic nucleus (STN) and the output nuclei, and reduced activity of the
      globus pallidus external (GPe) segment. These rate changes have been explained
      qualitatively in terms of the direct/indirect pathway model, involving
      projections of distinct striatal populations to the output nuclei and GPe.
      Although these populations partly overlap, evidence suggests dopamine depletion
      differentially affects cortico-striato-pallidal connection strengths to the two
      pallidal segments. Dopamine loss may also decrease the striatal signal-to-noise
      ratio, reducing both corticostriatal coupling and striatal firing thresholds.
      Additionally, nigrostriatal degeneration may cause secondary changes including
      weakened lateral inhibition in the GPe, and mesocortical dopamine loss may
      decrease intracortical excitation and especially inhibition. Here a mean-field
      model of the BGTCS is presented with structure and parameter estimates closely
      based on physiology and anatomy. Changes in model rates due to the possible
      effects of dopamine loss listed above are compared with experiment. Our results
      suggest that a stronger indirect pathway, possibly combined with a weakened
      direct pathway, is compatible with empirical evidence. However, altered
      corticostriatal connection strengths are probably not solely responsible for
      substantially increased STN activity often found. A lower STN firing threshold,
      weaker intracortical inhibition, and stronger striato-GPe inhibition help explain
      the relatively large increase in STN rate. Reduced GPe-GPe inhibition and a lower
      GPe firing threshold can account for the comparatively small decrease in GPe rate
      frequently observed. Changes in cortex, GPe, and STN help normalize the cortical
      rate, also in accord with experiments. The model integrates the basal ganglia
      into a unified framework along with an existing thalamocortical model that
      already accounts for a wide range of electrophysiological phenomena. A companion
      paper discusses the dynamics and oscillations of this combined system.

PMID- 19168075
TI  - Predicting the phenotypic response of resource-competing communities to
      environmental change.
AB  - We formulated responses in functional traits by competitive communities to
      continual environmental changes, and examined the association of the trait
      dynamics with species richness and interspecific competition. As an aggregate
      measure for community properties we employed the mean community trait value as
      the species traits averaged over an entire community with weighting by relative
      species abundances. For three particular types of community, in which there was
      competition for abiotic resources, competition for biotic resources, or species
      packing on an environmental gradient, we analytically proved that the responses
      of the mean community trait to environmental change were determined by the total
      trait range in the community but were weakly associated with the strength of
      competition and the number of species. These results were provided with
      simplifying assumptions that the species trait determining the resource utility
      equally spaced along an univariate resource axis and the competition between
      species was symmetrical between pairs of competing species and within the entire
      community. Some numerical simulations based on stochastically-generated
      communities and randomly-sampled natural communities indicated that relaxation of
      the simplifying assumptions did not considerably violate the above conclusion.
      The suggested determinacy of trait dynamics with variable species richness and
      competition regime implies that aggregated description of communities in terms of
      trait distributions among composite species is relevant in predicting community
      responses, in terms of functional traits and ecosystem function, to environmental
      changes.

PMID- 19168076
TI  - On the long-run sensitivity of probabilistic Boolean networks.
AB  - Boolean networks and, more generally, probabilistic Boolean networks, as one
      class of gene regulatory networks, model biological processes with the network
      dynamics determined by the logic-rule regulatory functions in conjunction with
      probabilistic parameters involved in network transitions. While there has been
      significant research on applying different control policies to alter network
      dynamics as future gene therapeutic intervention, we have seen less work on
      understanding the sensitivity of network dynamics with respect to perturbations
      to networks, including regulatory rules and the involved parameters, which is
      particularly critical for the design of intervention strategies. This paper
      studies this less investigated issue of network sensitivity in the long run. As
      the underlying model of probabilistic Boolean networks is a finite Markov chain,
      we define the network sensitivity based on the steady-state distributions of
      probabilistic Boolean networks and call it long-run sensitivity. The steady-state
      distribution reflects the long-run behavior of the network and it can give
      insight into the dynamics or momentum existing in a system. The change of steady
      state distribution caused by possible perturbations is the key measure for
      intervention. This newly defined long-run sensitivity can provide insight on both
      network inference and intervention. We show the results for probabilistic Boolean
      networks generated from random Boolean networks and the results from two real
      biological networks illustrate preliminary applications of sensitivity in
      intervention for practical problems.

PMID- 19168077
TI  - Stochastic sampling of interaction partners versus deterministic payoff
      assignment.
AB  - Evolutionary game dynamics describes how successful strategies spread in a
      population. In well-mixed populations, the usual assumption, e.g. underlying the
      replicator dynamics, is that individuals obtain a payoff from interactions with a
      representative sample of the population. This determines their fitness. Here, we
      analyze a situation in which payoffs are obtained through a single interaction,
      so that individuals of the same type can have different payoffs. We show
      analytically that for weak selection, this scenario is identical to the usual
      approach in which an individual interacts with the whole population. For strong
      selection, however, differences arise that are reflected in the fixation
      probabilities and lead to deviating evolutionary dynamics.

PMID- 19168078
TI  - Maximum likelihood estimation of neutral model parameters for multiple samples
      with different degrees of dispersal limitation.
AB  - In a recent paper, I presented a sampling formula for species abundances from
      multiple samples according to the prevailing neutral model of biodiversity, but
      practical implementation for parameter estimation was only possible when these
      samples were from local communities that were assumed to be equally dispersal
      limited. Here I show how the same sampling formula can also be used to estimate
      model parameters using maximum likelihood when the samples have different degrees
      of dispersal limitation. Moreover, it performs better than other, approximate,
      parameter estimation approaches. I also show how to calculate errors in the
      parameter estimates, which has so far been largely ignored in the development of
      and debate on neutral theory.

PMID- 19168079
TI  - A computable expression of closure to efficient causation.
AB  - In this paper, we propose a mathematical expression of closure to efficient
      causation in terms of lambda-calculus; we argue that this opens up the
      perspective of developing principled computer simulations of systems closed to
      efficient causation in an appropriate programming language. An important
      implication of our formulation is that, by exhibiting an expression in lambda
      calculus, which is a paradigmatic formalism for computability and programming, we
      show that there are no conceptual or principled problems in realizing a computer
      simulation or model of closure to efficient causation. We conclude with a brief
      discussion of the question whether closure to efficient causation captures all
      relevant properties of living systems. We suggest that it might not be the case,
      and that more complex definitions could indeed create crucial some obstacles to
      computability.

PMID- 19168080
TI  - Low red cell production may protect against severe anemia during a malaria
      infection--insights from modeling.
AB  - The malaria parasite causes lysis of red blood cells, resulting in anemia, a
      major cause of mortality and morbidity. Intuitively, one would expect the
      production of red blood cells to increase in order to compensate for this loss.
      However, it has been observed that this response is weaker than would be
      expected. Furthermore, iron supplementation for iron deficient children in
      malaria endemic regions can paradoxically adversely affect the clinical outcome
      of malaria infection. A possible explanation may lie in the preference that some
      malaria parasites show for infecting immature red blood cells (reticulocytes). In
      the presence of a parasite preference for immature red cells, a rise in red cell
      production can 'fuel the fire' of infection by increasing the availability of the
      parasite's preferred target cell. We present a mathematical model of red blood
      cell production and infection in order to explore this hypothesis. We assess the
      effect of varying the reticulocyte replacement rate and preference of the
      parasite for reticulocytes on four key outcome measures assessing anemia and
      parasitemia. For a given level of parasite preference for reticulocytes we
      uncover an optimal erythropoietic response which minimizes disease severity.
      Increasing red blood cell production much above this optimum confers no benefit
      to the patient, and in fact can increase the degree of anemia and parasitemia.
      These conclusions are consistent with epidemiological studies demonstrating that
      both iron deficiency and anemia are protective against severe malaria, whilst
      iron supplementation in malaria endemic regions is with an increased number of
      malaria related adverse effects. Thus, suppression of red blood cell production,
      rather than being an unfortunate side effect of inflammation, may be a host
      protective effect against severe malarial anemia.

PMID- 19168081
TI  - Demographic analysis of Hubbell's neutral theory of biodiversity.
AB  - Hubbell's neutral model is increasingly applied in both theoretical and empirical
      studies but so far little attention has been paid to the ecological mechanisms
      that determine species diversity in neutral communities. In this contribution we
      use a stochastic individual-based Markovian model to provide an explicit
      derivation of Hubbell's local community model from the fundamental processes of
      reproduction, mortality, and immigration, and show that such derivation provides
      important insights on the mechanisms regulating species diversity that cannot be
      obtained from the original model and its previous extensions. One important
      insight is that the basic parameters of Hubbell's model, community size (J) and
      the probability that a dying individual will be replaced by an immigrant (m),
      cannot be considered independent and that their interdependency leads to a
      counterintuitive trade-off between community size and species diversity. We
      further demonstrate that Hubbell's treatment of community size as a free
      parameter hides fundamental mechanisms that influence species diversity through
      their effect on the size of the community. For example, while in Hubbell's model
      immigration can only increase species diversity by promoting colonization rates,
      the demographic derivation shows that immigration can also promote species
      diversity by reducing extinction rates. Our demographic derivation also unifies
      previous contrasting predictions about the effect of reproduction on species
      diversity by showing that both positive and negative effects are possible, and
      that the balance between the two effects depends on the size of the community.
      The demographic derivation also reconciles an apparent contradiction between
      Hubbell's theory and patch occupancy theory, and integrates three previously
      proposed mechanisms of species diversity, the More Individuals Hypothesis, the
      rescue effect, and the dilution effect, within a single, unified framework.

PMID- 19168083
TI  - The parageneses thermodynamic analysis of chemoautotrophic CO2 fixation archaic
      cycle components, their stability and self-organization in hydrothermal systems.
AB  - The parageneses physico-chemical analysis based on a method of thermodynamic
      potentials has been used to study the system of C-H-O organic compounds, which
      are, in particular, components of biomimetically built primordial cycles of
      carbon dioxide chemoautotrophic fixation. Thermodynamic data for aqueous organic
      compounds allowed one to construct the chemical potential diagrams and establish
      the areas of thermodynamic stability (facies) of components of CO2 fixation
      pathways in hydrothermal systems, in particular, a reductive citric cycle (RCC),
      3-hydroxypropionate cycle (3-HPC) and acetyl-CoA pathway. An alternative deep
      source of carbon (hydrocarbons) proved by the data on endogenous emission of
      hydrocarbons in hydrothermal fields of oceanic ridges was suggested. The system
      was determined, which combines hydrocarbons, CO2 and components of RCC, 3-HPC and
      acetyl-CoA pathway with characteristic parageneses of methane and ethylene with
      acetate in two-component CH4-CO2 and C2H4-O2 subsystems, respectively. The
      thermodynamic analysis of a redox mode at various pressures and temperatures
      allowed one to uniquely determine hydrocarbon-organic system able to
      independently generate acetate and succinate at oxidation of deep hydrothermal
      hydrocarbon fluids emerging on sea surface. The limits for thermodynamic
      stability of CO2 archaic fixation (CAF) components responsible for generation and
      self-organization in hydrothermal environment was identified. The tentative
      integrated system of CAF was developed as a combined acetyl-CoA pathway, 3-HPC
      and RCC containing a succinate-fumarate core, capable of switching electron flow
      in forward or reverse direction depending on redox potential of geochemical
      environment that is governed by the (CH)2(COOH)2+H2=(CH2)2(COOH)2 reaction. This
      core is a "redox switch", which is sensitive to certain conditions of
      hydrothermal environment and defines electron flow direction. The redox
      geochemical mode caused by temperature, pressure, composition of a hydrothermal
      fluid and a mineralogical setting defines stability of CAF cycle components in
      paragenesis with hydrocarbons and possibility of cycle self-organization.

PMID- 19168084
TI  - Can splenocytes enhance pancreatic beta-cell function and mass in 90%
      pancreatectomized rats fed a high fat diet?
AB  - AIMS: Recent studies have shown that splenocytes may act as a possible neogenic
      source with regard to beta-cells in rodent diabetic models. Accordingly, we
      sought to determine whether splenocytes played an important role in promoting
      beta-cell function and mass among type 2 diabetic rats with and without spleen.
      MAIN METHODS: We randomly divided female 90% pancreatectomized (Px) Sprague
      Dawley rats into three groups: splenectomy (SPX), splenectomy plus the injection
      of male splenocytes (SPI), and no splenectomy (NSP). They were administered with
      40 energy percent fat diets over the course of five weeks. At the end of the
      experimental period, insulin secretion capacity was measured by hyperglycemic
      clamp. At 6 h after BrdU(+) injection, the pancreas was prepared with 4%
      paraformaldehyde in order to perform immunohistochemistry. KEY FINDINGS: SPX
      increased and sustained serum glucose levels more than NSP and SPI during oral
      glucose tolerance testing. During hyperglycemic clamp, first and second phase
      insulin secretion decreased in the SPX rats while splenocyte injections
      counteracted this. Beta-cell mass in the SPX group was reduced more than among
      NSP and SPI. This was the result of a decrease in the number of small beta-cell
      clusters in SPX, which is indicative of a decrease in beta-cell neogenesis.
      SIGNIFICANCE: Splenocytes play an important role with regard to the neogenesis of
      beta-cells in insulin deficient type 2 diabetic rats, although they are not
      critical for beta-cell regeneration.

PMID- 19168085
TI  - Normalization of horizontal pseudoneglect following right, but not left, upper
      limb amputation.
AB  - OBJECTIVES: Subjects who have suffered limb amputations are known to have
      physiological alterations of their body's representation, or schema. Such changes
      of brain function might alter the right-left spatial allocation of attention. The
      goal of this study was to learn if, compared to normal subjects, limb amputees
      had alterations of right-left spatial attention. METHODS: The subjects were
      veterans with amputation of one upper or lower limb. All subjects performed
      horizontal line bisections in their left, middle and right body-centered space.
      RESULTS: Following right upper limb amputation, there appears to be a reduction
      of the normal left-sided bias (pseudoneglect) primarily for lines presented in
      the right body hemispace. CONCLUSIONS: This amputation-induced alteration of
      attentional bias might be related to changes in the body schema, a compensatory
      strategy, or alterations of scanning patterns. Further studies are needed to
      reproduce these results and to learn the underlying brain mechanism.

PMID- 19168086
TI  - Ventral and dorsal stream contributions to the online control of immediate and
      delayed grasping: a TMS approach.
AB  - According to Milner and Goodale's theory of the two visual streams, the dorsal
      (action) stream controls actions in real-time, whereas the ventral (perceptual)
      stream stores longer-term information for object identification. By this account,
      the dorsal stream subserves actions carried out immediately. However, when a
      delay is required before the response, the ventral (perceptual) stream is
      recruited. Indeed, a neuroimaging study from our lab has found reactivation of an
      area within the ventral stream, the lateral occipital (LO) cortex, at the time of
      action even when no visual stimulus was present. To tease apart the contribution
      of specific areas within the dorsal and ventral streams to the online control of
      grasping under immediate and delayed conditions, we used transcranial magnetic
      stimulation (TMS) to the anterior intraparietal sulcus (aIPS) and to LO. We show
      that while TMS to aIPS affected grasp under both immediate and delayed
      conditions, TMS to LO influenced grasp only under delayed movement conditions.
      The effects of TMS were restricted to early movement kinematics (i.e. within 300
      ms) due to the transient nature of TMS, which was always delivered simultaneous
      with movement onset. We discuss the implications of our findings in relation to
      interactions between the dorsal and ventral streams.

PMID- 19168087
TI  - A review on environmental factors regulating arsenic methylation in humans.
AB  - Subjects exposed to arsenic show significant inter-individual variation in
      urinary patterns of arsenic metabolites but insignificant day-to-day intra
      individual variation. The inter-individual variation in arsenic methylation can
      be partly responsible for the variation in susceptibility to arsenic toxicity.
      Wide inter-ethnic variation and family correlation in urinary arsenic profile
      suggest a genetic effect on arsenic metabolism. In this paper the environmental
      factors affecting arsenic metabolism are reviewed. Methylation capacity might
      reduce with increasing dosage of arsenic exposure. Furthermore, women, especially
      at pregnancy, have better methylation capacity than their men counterparts,
      probably due to the effect of estrogen. Children might have better methylation
      capacity than adults and age shows inconsistent relevance in adults. Smoking and
      alcohol consumption might be associated with a poorer methylation capacity.
      Nutritional status is important in the methylation capacity and folate may
      facilitate the methylation and excretion of arsenic. Besides, general health
      conditions and medications might influence the arsenic methylation capacity; and
      technical problems can cause biased estimates. The consumption of seafood,
      seaweed, rice and other food with high arsenic contents and the extent of cooking
      and arsenic-containing water used in food preparation may also interfere with the
      presentation of the urinary arsenic profile. Future studies are necessary to
      clarify the effects of the various arsenic metabolites including the trivalent
      methylated forms on the development of arsenic-induced human diseases with the
      consideration of the effects of confounding factors and the interactions with
      other effect modifiers.

PMID- 19168088
TI  - Tandem fluorescent proteins as enhanced FRET-based substrates for botulinum
      neurotoxin activity.
AB  - The light chain of botulinum neurotoxin A (BoNT/A-LC) is a zinc-metalloprotease
      that requires two extended exosites for optimal substrate binding and recognition
      of its intracellular target SNAP25. CFP and YFP connected through SNAP25 peptide
      (141-206) containing both exosites (CsY) has been used in a FRET-based assay for
      BoNT/A. To further improve the FRET efficiency in this BoNT/A substrate for in
      vitro high-throughput assays, we explored the feasibility of enhancing the
      capture of CFP emission by doubling the number of YFP acceptors. In comparison to
      CsY, the tandem fluorescence substrates CsYY and YsCsY enhanced the ratiometric
      fluorescence signal between YFP and CFP. YsCsY, containing two substrate sites,
      offered the greatest fluorometric change upon toxin-catalyzed cleavage. In
      addition to known approaches for enhancing fluorescence yield through various
      mutations, this alternative tandem substrate approach can boost the FRET signal
      and is particularly useful for substrates requiring extensive exosite recognition
      for specificity.

PMID- 19168089
TI  - Influence of the A and B subunits of cholera toxin (CT) and Escherichia coli
      toxin (LT) on TNF-alpha release from macrophages.
AB  - In this study an in vitro model was developed with the aim of investigating the
      modulatory effect of cholera toxin (CT) and its counterpart the heat labile toxin
      of Escherichia coli (LT) on TNF-alpha release induced by murine macrophages and
      primary human monocytes. Previous studies have demonstrated that the enzymatic
      activity of CT and LT molecules can inhibit TNF-alpha release by macrophages. The
      results obtained in this study showed that CT and LT are both, in a dose
      dependent manner, able either to induce or inhibit TNF-alpha release by murine
      macrophages and primary human monocytes. The results also showed that recombinant
      B subunits of CT and LT in the absence of their A subunit induce high levels of
      TNF-alpha release by macrophages and, in addition, increase the level of TNF
      alpha release induced by LPS. The ability of both B subunits (CTB and LTB) in
      inducing TNF-alpha release by macrophages is not related to the level of LPS
      contamination, since direct measurements of LPS made in the samples employed in
      this study showed only traces of LPS (3.4 x 10(-8) EU/ml) which is in our system
      does not induce TNF-alpha release by macrophages. In contrast to the results
      obtained with the B subunits, incubation of cells with the A subunit of CT (CTA)
      inhibit TNF-alpha release induced by native CT, native LT, recombinant LTB and
      LPS. This inhibitory effect must be related to the activity of the A subunit
      since viability tests performed in terms of metabolic rate demonstrated that high
      concentrations of CTA are not toxic to the cells. The data presented herein
      demonstrate that the A subunits of CT and LT have an inhibitory effect on TNF
      alpha release in macrophages, whereas their B subunits have a stimulatory effect
      on TNF-alpha. The results also suggest that the dose dependent bi-modal effect of
      native CT and native LT on TNF-alpha release by macrophages is a result of the
      combined effect of their individual A and B subunits.

PMID- 19168090
TI  - The significance of PTEN's protein phosphatase activity.

PMID- 19168091
TI  - Hypothesis testing and the EU-Dap evaluation of the Unplugged curriculum.

PMID- 19168092
TI  - Analyzing the occurrence of falls and its risk factors: some considerations.
AB  - OBJECTIVE: Falls are a common problem facing elderly people and are associated
      with considerable mortality and morbidity. The objective of this paper is to
      study the application of the conditional model as an alternative for the
      statistical analysis of the occurrence of falls and their associated factors.
      METHODS: Cohort study. We select all ninety-eight residents admitted during the
      year 2007 in a long-term care centre, Seville, Spain. Five models were fitted:
      Negative binomial, standard Cox for the first fall, standard Cox for all falls,
      Andersen-Gill model, and Prentice-Williams-Peterson model. RESULTS: The crude
      incidence rate of falls was 26.3 per 100 person-months. The median time to fall
      decreases depending on the falls previously experienced, while the hazard rises.
      The AG's standard errors are between 1.4 and 2.7 times bigger than those
      estimated by Standard Cox. The major differences between marginal models were in
      the "Barthel 25-60" coefficient, where the conditional model attributed an
      HR=2.39 versus HR=3.77 estimated by the extension model. CONCLUSION: As the risk
      increases depending on the falls previously suffered by an individual, the PWP
      conditional model becomes an interesting alternative for obtaining unbiased and
      precise estimations of coefficients associated with possible risk factors of
      falls.

PMID- 19168093
TI  - An update on preventive and regenerative therapies in diabetes mellitus.
AB  - Type 1A (immune-mediated) and type 2 diabetes mellitus are two of the most common
      severe chronic illnesses, affecting over 230 million people worldwide with an
      estimated global prevalence of 5.1%. Although type 1 and type 2 diabetes differ
      greatly in modes of pathogenesis, these illnesses share a common pathology and
      consequences characterized by loss of functional beta-cell mass and subsequent
      dysregulation of carbohydrate and lipid metabolism. Since therapy for diabetes
      and the associated complications poses enormous public health and economic
      burdens, novel preventive and regenerative therapies have emerged in the past
      decade with the aim to preserve beta-cell mass and delay the onset of diabetes.
      The goal of this review is to provide a comprehensive overview of current efforts
      in the fight against diabetes, and attempts to document all strategies that have
      emerged in clinical studies within the past 25 years. First, strategies to
      identify individuals at risk, ranging from whole-genome scans to autoantibody
      screening, will be discussed. Second, novel approaches to prevent or delay the
      onset of disease will be covered. Particular focus is given on emerging
      strategies for individuals at risk for type 1 diabetes that target T-cell
      regulation and induction of tolerance, while new pharmaceutical concepts in
      combination with lifestyle interventions are discussed within the scope of type 2
      diabetes prevention. Lastly, important efforts to halt disease progression with
      emphasis on beta-cell regeneration are presented.

PMID- 19168094
TI  - Predicting therapeutic efficacy - experimental pain in human subjects.
AB  - The pharmaceutical industry faces tough times. Despite tremendous advances in the
      science and technology of new lead identification and optimization, attrition
      rates for novel drug candidates making it into the clinic remain unacceptably
      high. A seamless boundary between basic preclinical and clinical arms of the
      discovery process, embodying the concept of 'translational research' is viewed by
      many as the way forward. The rational application of human experimental pain
      models in early clinical development is reviewed. Capsaicin, UV-irradiation and
      electrical stimulation methods have each been used to establish experimental
      hyperalgesia in Phase-I human volunteers and the application of these approaches
      is discussed in the context of several pharmacological examples. However, data
      generated from such studies must be integrated into a well-conceived and executed
      series of Phase-II efficacy trials in patients in order to derive maximal
      benefit. The challenges involved in optimal Phase-II/III trial design are
      reviewed with specific attention to the issues of sample size and placebo
      response. Finally, the application and potential of cortical EEG studies are
      discussed as an objective alternative to more conventional pain assessment tools
      with specific examples of how this technique has been applied to the study of
      NSAID and opiate-based therapeutics.

PMID- 19168095
TI  - Acquisition of brains from the African elephant (Loxodonta africana): perfusion
      fixation and dissection.
AB  - The current correspondence describes the in situ perfusion-fixation of the brain
      of the African elephant. Due to both the large size of proboscidean brains and
      the complex behaviour of these species, the acquisition of good quality material
      for comparative neuroanatomical analysis from these species is important. Three
      male African elephants (20-30 years) that were to be culled as part of a larger
      population management strategy were used. The animals were humanely euthanized
      and the head removed from the body. Large tubes were inserted into to the carotid
      arteries and the cranial vasculature flushed with a rapid (20 min) rinse of 100 l
      of cold saline (4 degrees C). Following the rinse the head was perfusion-fixed
      with a slower rinse (40 min) of 100 l of cold (4 degrees C) 4% paraformaldehyde
      in 0.1M phosphate buffer. This procedure resulted in well-fixed neural and other
      tissue. After perfusion the brains were removed from the skull with the aid of
      power tools, a procedure taking between 2 and 6h. The brains were immediately
      post-fixed in the same solution for 72 h at 4 degrees C. The brains were
      subsequently placed in a sucrose solution and finally an antifreeze solution and
      are stored in a -20 degrees C freezer. The acquisition of high quality neural
      material from African elephants that can be used for immunohistochemistry and
      electron microscopy is of importance in understanding the "hardware" underlying
      the behaviour of this species. This technique can be used on a variety of large
      mammals to obtain high quality material for comparative neuroanatomical studies.

PMID- 19168096
TI  - Autophagy in cells of the blood.
AB  - Autophagy is a conserved proteolytic mechanism that degrades cytoplasmic material
      including cell organelles. The importance of autophagy for cell homeostasis and
      survival has long been appreciated. Recent data suggest that autophagy is also
      involved in non-metabolic functions that particularly concern blood cells. Here,
      we review these findings, which point to an important role of autophagy in
      several cellular functions related to host defense.

PMID- 19168097
TI  - Expression profiles of three novel sensory guanylate cyclases and guanylate
      cyclase-activating proteins in the zebrafish retina.
AB  - Three membrane bound sensory guanylate cyclases are expressed in photoreceptor
      cells of the developing and adult zebrafish retina. First appearance of mRNA
      transcripts was detected by in situ hybridization techniques for all guanylate
      cyclases between 3 and 4 days post fertilization (dpf), but only one isoform
      (guanylate cyclase 3) appeared to be specifically expressed in cones of the adult
      retina. Transcripts of three cone specific guanylate cyclase-activating proteins
      (zGCAP3, zGCAP4 and zGCAP7) were also detected at 3-4 dpf. The expression onset
      of the guanylate cyclases and these neuronal calcium sensor proteins mainly
      overlapped. High guanylate cyclase activities in larval eye preparations and the
      precisely controlled coexpression of guanylate cyclases and zGCAPs coincide with
      the onset of visual function at 3-4 dpf.

PMID- 19168098
TI  - Membrane localization of RasGRP1 is controlled by an EF-hand, and by the GEF
      domain.
AB  - RasGRP1 is an exchange factor for membrane-localized Ras GTPases. Activation of
      RasGRP1 requires its translocation to membranes, which can be directly mediated
      by either its PT or C1 domains. RasGRP1 also has a pair of EF-hands which have
      been proposed to regulate RasGRP1 by sensing receptor-induced calcium fluxes. We
      determined that one of these EF-hands, EF1, is required for receptor-induced
      translocation of RasGRP1 to the plasma membrane in B cell lines. EF1 enables
      plasma membrane targeting of RasGRP1 by counteracting the SuPT domain, a negative
      regulator of the PT domain. Contrary to expectations, EF1-mediated translocation
      of RasGRP1 does not involve antigen receptor-induced intracellular calcium flux.
      Instead, alternative splicing affecting EF1 serves to modulate RasGRP1
      localization. Excision of an exon encoding part of EF1 selectively disables PT
      domain-mediated plasma membrane targeting of RasGRP1, without affecting C1 domain
      mediated localization to endomembranes. While EF1 specifically controls PT
      mediated plasma membrane targeting, the Ras binding site in the catalytic GEF
      domain of RasGRP1 is required for both PT-mediated plasma membrane targeting and
      C1-mediated localization to endomembranes. Positive feedback between its GEF
      domain and membrane-binding domains could be important for full activation of
      RasGRP1, with occupation of the Ras binding sites in the GEF domain resulting in
      functional liberation of the PT and C1 domains, and membrane binding by these
      domains serving to maintain the Ras-GEF interaction.

PMID- 19168099
TI  - The relationship between skill level and patterns in cardiac and respiratory
      activity during golf putting.
AB  - Individual differences in skill level during sport-related motor tasks, such as
      golf putting, can be related to not only performance, but also patterns in
      psychophysiological activity. The present study examined the similarities and
      differences in cardiac and respiratory activity among elite, experienced, and
      novice golfers. Participants attempted flat putts 2.4 m from the hole.
      Performance was better in elite and experienced golfers than in novice golfers.
      Compared to novice golfers, the experienced and elite golfers showed a pronounced
      phasic deceleration in heart rate immediately prior to the putt, greater heart
      rate variability in the very low frequency band, and a greater tendency to show a
      respiratory pattern of exhaling immediately prior to the putt. The
      psychophysiological patterns may be related to differences in attentional
      processes or task familiarity between the groups. The implications of the results
      for the assessment and training of athletes in precision sports are discussed.

PMID- 19168100
TI  - Conjugation of salmon calcitonin to a combed-shaped end functionalized
      poly(poly(ethylene glycol) methyl ether methacrylate) yields a bioactive stable
      conjugate.
AB  - Salmon calcitonin (sCT) was conjugated via its N-terminal cysteine to a comb
      shaped end-functionalized poly(poly(ethylene glycol) methyl ether methacrylate)
      (PolyPEG, 6.5 kDa), and to linear PEG (5 kDa). Conjugate molecular weight and
      purity was assessed by SEC-HPLC and MALDI-TOF MS. Bioactivity of conjugates was
      measured by cyclic AMP assay in T47D cells. Calcium and calcitonin levels were
      measured in rats following intravenous injections. Stability of conjugates was
      tested against serine proteases, intestinal and liver homogenates and serum.
      Cytotoxicity of conjugates was assessed by lactate dehydrogenase (LDH) assay and
      by haemolytic assay of rat red blood cells. Results showed that the two
      conjugates were of high purity with molecular weights similar to predictions.
      Both conjugates retained more than 85% bioactivity in vitro and had nanomolar
      EC(50) values similar to sCT. While both sCT-PolyPEG(6.5 K) and sCT-PEG(5 K) were
      resistant to metabolism by serine proteases, homogenates and serum, PolyPEG (6.5
      K) was more so. Although both conjugates reduced serum calcium to levels similar
      to those achieved with sCT, PolyPEG(6.5 K) extended the T(1/2) and AUC of serum
      sCT over values achieved with sCT-PEG and sCT itself. None of PolyPEG, PEG or
      methacrylic acid displayed significant cytotoxicity. PolyPEG may therefore have
      potential to improve pharmacokinetic profiles of injected peptides.

PMID- 19168101
TI  - Sustained and efficient porphyrin generation in vivo using dendrimer conjugates
      of 5-ALA for photodynamic therapy.
AB  - The use of endogenous protoporphyrin IX (PpIX) after administration of 5
      aminolaevulinic acid (ALA) has led to many applications in photodynamic therapy
      (PDT). However the efficacy of ALA-PDT is sub-optimal for thicker tumours and
      improved ALA delivery and therapeutic response are required. We have investigated
      the conjugation of ALA to a second-generation dxcendrimer for enhancing porphyrin
      synthesis in vitro and in vivo in a murine tumour model using systemic i.p.
      administration. In vitro, the dendrimer was more efficient than ALA for porphyrin
      synthesis at low concentrations in good correlation with higher cellular ALA
      dendrimer accumulation. In vivo, the porphyrin kinetics from ALA exhibited an
      early peak between 3 and 4 h in most tissues, whereas the dendrimer induced
      sustained porphyrin production for over 24 h and basal values were not reached
      until 48 h after administration. Integrated porphyrin accumulation from the
      dendrimer and ALA, at equivalent molar ratios, was comparable showing that the
      majority of ALA residues were liberated from the dendrimer. The porphyrin
      kinetics appear to be governed by the rate of enzymatic cleavage of ALA from the
      dendrimer, which is consistent with in vitro results. ALA dendrimers may be
      useful for metronomic PDT, and multiple low-dose ALA-PDT treatments.

PMID- 19168102
TI  - CpG oligodeoxynucleotide-based therapy of lymphoid malignancies.
AB  - Preclinical and early clinical trials indicate synthetic oligodeoxynucleotides
      containing unmethylated CG dinucleotides (CpG ODN) have potent immunostimulatory
      effects. CpG ODN are being explored as immune adjuvants in vaccination strategies
      and as potential treatments for a wide variety of disorders including cancer and
      asthma. Therapeutic approaches designed to take advantage of this potent class of
      agents are based largely on the ability of CpG ODN to activate professional
      antigen presenting cells (APCs) that express the target receptor - Toll-Like
      Receptor 9 (TLR9). B-cell malignancies are unique in that the malignant cells
      themselves express TLR9. CpG ODN can have a direct effect on the malignant B
      cells and lead to activation induced cell death. CpG ODN also alter the phenotype
      of target malignant B cells as indicated by upregulation of MHC,
      immunostimulatory molecules, and antigens that serve as targets for other
      approaches to lymphoma immunotherapy such as CD20. B cell malignancies are also
      relatively sensitive to the cytokines that are produced by dendritic cells in
      response to CpG ODN. Thus, B cell malignancies appear to be uniquely sensitive to
      CpG ODN because of both the direct and indirect effects the CpG ODN on target
      cells and the sensitivity of B cell malignancies to an immune response.
      Preclinical studies support further exploration of the potential of CpG ODN as a
      component of therapy for lymphoid malignancies. Ongoing clinical trials are
      exploring the potential of CpG ODN, both alone and in combination with other
      agents.

PMID- 19168103
TI  - Enhancing the therapeutic efficacy of CpG oligonucleotides using biodegradable
      microparticles.
AB  - Oligonucleotides, with specific sequence surrounding CpG motifs, appear to be
      very effective for the induction of a potent Th1 responses. This molecule
      represents pathogen-associated molecular patterns (PAMPs) that allows the
      pathogen recognition receptors (PRRs) present on innate immune cells to recognize
      them and become activated. PAMPs and related compounds are often labelled as
      immunopotentiators, allowing a clear distinction between them and particulate
      delivery systems such as emulsions, liposomes, virus-like particles and
      microparticles. Microparticles prepared from biodegradable, biocompatible
      polyesters, and poly (lactide co-glycolide) (PLG). They have been proven to be a
      good particulate delivery system for the co-delivery of antigens and adjuvants.
      PLG has been used in humans for many years as a resorbable suture material and
      controlled-release drug delivery systems. It has been demonstrated that antigen
      presenting cells (APCs) efficiently uptake the PLG microparticles ( approximately
      1 microm) both in vivo and in vitro. After uptake, the PLG subsequently induces
      an antigen specific CTL response in rodents. Several groups, including our group,
      have evaluated CpG as an immunopotentiator in various formulations and delivery
      systems (i.e. emulsions and particulate systems). This review will discuss in
      detail the work conducted so far with CpG using PLG microparticles as a delivery
      system. We will also discuss the advantages and enhancement of immune properties
      of formulating CpG (soluble, adsorbed, and encapsulated forms) with PLG
      microparticles along with future directions for these microparticles with CpG.

PMID- 19168104
TI  - Vaccination in adults with auto-immune disease and/or drug related immune
      deficiency: results of the GEVACCIM Delphi survey.
AB  - INTRODUCTION: There are insufficient data regarding the efficacy and safety of
      vaccination in patients with auto-immune disease (AID) and/or drug-related immune
      deficiency (DRID). The objective of this study was to obtain professional
      agreement on vaccine practices in these patients. METHODS: A Delphi survey was
      carried out with physicians recognised for their expertise in vaccinology and/or
      the caring for adult patients with AID and/or DRID. For each proposed vaccination
      practice, the experts' opinion and level of agreement were evaluated. RESULTS:
      The proposals relating to patients with AID specified: the absence of risk of AID
      relapse following vaccination; the possibility of administering live virus
      vaccines (LVV) to patients not receiving immunosuppressants; the pertinence of
      determining protective antibody titre before vaccination; the absence of need for
      specific monitoring following the vaccination. The proposals relating to patients
      with DRID specified that a 3-6 month delay is needed between the end of these
      treatments and the vaccination with LVV. There is no contraindication to
      administering LVV in patients receiving systemic corticosteroids prescribed for
      less than two weeks, regardless of their dose, or at a daily dose not exceeding
      10mg of prednisone, if this involves prolonged treatment. Out of 14 proposals,
      the level of agreement between the experts was "very good" for eleven, and "good"
      for the remaining three. CONCLUSION: Proposals for vaccine practices in patients
      with AID and/or DRID should aid with decision-making in daily medical practice
      and provide better vaccine coverage for these patients.

PMID- 19168105
TI  - Immunogenicity of recombinant Modified Vaccinia Ankara following a single or
      multi-dose vaccine regimen in rhesus monkeys.
AB  - Modified Vaccinia Ankara (MVA) is a replication-defective strain of vaccinia
      virus (VV) that is being investigated in humans as an alternative vaccine against
      smallpox. Understanding the parameters of a MVA vaccine regimen that can
      effectively enhance protective immunity will be important for clinical
      development. The present studies utilize cohorts of rhesus monkeys immunized with
      recombinant MVA (rMVA) or recombinant VV (rVV) vaccine vectors to investigate the
      magnitude, breadth, and durability of anti-VV immunity elicited by a single or
      multi-dose vaccine regimen. These data demonstrate that a single immunization
      with rMVA elicits weaker cellular and humoral immunity compared to a single
      inoculation with rVV. However, vaccine-elicited antibody responses, but not T
      cell responses, are significantly enhanced with repeated immunizations of rMVA.
      Importantly, only monkeys receiving up to four inoculations with rMVA generated
      neutralizing antibody (NAb) responses that were comparable in magnitude and
      durability to those elicited in monkeys receiving two inoculations with rVV.
      These data also show that the breadth of antibody responses against protein
      antigens associated with two antigenically distinct forms of infectious VV are
      similar in rMVA- and rVV-immunized monkeys. Together, these studies suggest that
      a multi-dose vaccine regimen utilizing up to four inoculations of MVA generates
      robust and durable antibody-mediated immunity comparable to that elicited by
      replication-competent VV.

PMID- 19168106
TI  - The influence of carrier protein on the immunogenicity of simultaneously
      administered conjugate vaccines in infants.
AB  - Continuing additions of new vaccines to routine infant vaccination schedules have
      prompted concerns about potential interactions between vaccine components
      reducing desired protective effects. One hypothesis is that increasing loads of
      carrier protein may interfere with immune responses to polysaccharide components
      of co-administered glycoconjugate vaccines. Based upon a critical appraisal of
      existing evidence, however, neither carrier protein type nor dose adequately
      explains observed interference. Moreover, in five clinical trials, enhancement of
      anti-polyribosylribitol phosphate Haemophilus influenzae type b antibody has been
      demonstrated after co-administration of monovalent meningococcal C conjugate
      vaccine with tetanus toxoid carrier. Empirical observations do not fit well with
      carrier-induced epitope suppression as an underlying mechanism of interference.
      Thus, co-administration of conjugate vaccines can have positive as well as
      negative effects, and predictors of vaccine interactions are still lacking.

PMID- 19168107
TI  - A CMV DNA vaccine primes for memory immune responses to live-attenuated CMV
      (Towne strain).
AB  - CMV-seronegative subjects vaccinated intramuscularly or intradermally with a DNA
      vaccine encoding pp65, IE1, and gB were administered live-attenuated CMV (Towne)
      to characterize immune priming by the DNA vaccine. CMV-specific memory T-cells
      (detected by standard ELISPOT assay in only 20% of subjects) were detected by IFN
      gamma cultured ELISPOT assay in 60% of subjects primed intramuscularly and
      correlated with immune responses after Towne. The median time to first pp65 T
      cell and gB antibody response after Towne was 14 days for DNA-primed subjects vs.
      28 days for controls administered Towne only (p=0.02 and 0.03, respectively).
      Furthermore, there was a trend toward more DNA-vaccinated subjects than controls
      developing a gB-specific IFN-gamma T-cell response after Towne administration
      (47% vs. 0%, p=0.06).

PMID- 19168108
TI  - Attenuation of coxsackievirus B3 by VP2 mutation and its application as a vaccine
      against virus-induced myocarditis and pancreatitis.
AB  - Coxsackievirus B3 (CVB3) is a common agent of viral myocarditis, a major cause of
      sudden cardiac death, and ultimately dilated cardiomyopathy. However, there is no
      vaccine in clinical use. In this study, we identified the conserved amino acid
      sequences in the C-terminal region of the VP2 of the coxsackievirus B group and
      some echoviruses. The mutant virus, YYFF, with phenylalanines substituted for two
      tyrosines in these conserved sequences was highly attenuated in vivo and could
      induce a high neutralizing antibody titer and a cytotoxic T-lymphocyte response
      against CVB3. Thereby, mutant-virus-immunized mice showed a 100% survival rate
      and protection against inflammation of the heart and pancreas after lethal dose
      challenge. Thus, this mutant virus is a good candidate for an attenuated CVB3
      vaccine.

PMID- 19168109
TI  - Randomized-controlled phase II clinical trial of a bacterially expressed
      recombinant hepatitis E vaccine.
AB  - The candidate recombinant hepatitis E vaccine, HEV 239, protect monkeys against
      infection by hepatitis E virus (HEV). The safety and immunogenicity of the
      vaccine for humans was assessed in a randomized controlled phase II clinical
      trial. The study was conducted in an endemic area of southern China and consisted
      of a dose scheduling, involving 457 adults and a dose escalation component
      involving 155 high school students. The results showed that the vaccine is safe
      and immunogenic for humans and suggest that it could prevent new HEV infection.

PMID- 19168110
TI  - Delivery to the lower respiratory tract is required for effective immunization
      with Newcastle disease virus-vectored vaccines intended for humans.
AB  - Newcastle disease virus (NDV), an avian virus, is being evaluated for the
      development of vectored human vaccines against emerging pathogens. Previous
      studies of NDV-vectored vaccines in a mouse model suggested their potency after
      delivery by injection or by the intranasal route. We compared the efficacy of
      various routes of delivery of NDV-vectored vaccines in a non-human primate model.
      While delivery of an NDV-vectored vaccine by the combined
      intranasal/intratracheal route elicited protective immune responses, delivery by
      the subcutaneous route or the intranasal route alone elicited limited or no
      protective immune responses, suggesting the necessity for vaccine delivery to the
      lower respiratory tract. Furthermore, direct comparison of a vaccine based on an
      NDV mesogenic strain (NDV-BC) with a similarly designed NDV vector based on a
      modified lentogenic strain carrying a polybasic F cleavage site (NDV-VF)
      suggested that the two NDV strains were similar in immunogenicity and were
      equally protective.

PMID- 19168111
TI  - Efficacy of pneumococcal conjugate vaccine against PCR-positive acute otitis
      media.
AB  - We aimed to assess the efficacy of a pneumococcal conjugate vaccine against acute
      otitis media (AOM) positive by pneumolysin-PCR (Ply-PCR). 1662 infants vaccinated
      with PncCRM or control vaccine using random allocation were followed for AOM up
      to 24 months of age. When AOM was diagnosed a middle ear fluid sample was
      obtained for etiological assays. During the per protocol follow-up period the
      PncCRM vaccine efficacy was 19% against Ply-PCR-positive AOM but only 3% when
      culture-positive cases were excluded. The data do not support effect of PncCRM on
      AOM in which only Ply-PCR suggests pneumococcal etiology.

PMID- 19168112
TI  - Effects of the polysaccharide beta-glucan on clastogenicity and teratogenicity
      caused by acute exposure to cyclophosphamide in mice.
AB  - Alterations that could lead to the cancer development may also be related to an
      adverse development of offspring in experimental animals. Some functional foods,
      which contain the polysaccharide beta-glucan, have been described as being
      effective in the prevention of clastogenic damage. Based on that finding, the aim
      of the present study was to determine the efficacy of this sugar polymer in the
      mutagenic and teratogenic damage control. Two sets of females, pregnant and non
      pregnant, were evaluated. The results indicated that beta-glucan was effective in
      preventing clastogenic damage in pregnant as well as non-pregnant females. In
      addition, pregnant females were more susceptible to mutagenic damage. However,
      teratogenic effects were not prevented effectively, although there was a trend
      toward a reduction in level of malformations. Despite beta-glucan did not prevent
      malformations, it increased fetal viability and reduced number of post
      implantation losses and resorption, thereby enhancing reproductive performance in
      females.

PMID- 19168113
TI  - Anxiolytic-like effect of phytoestrogen genistein in rats with long-term absence
      of ovarian hormones in the black and white model.
AB  - Postmenopause is mainly characterized by a reduction of ovarian hormones, which
      is accompanied by a major incidence of physical disorders and mood swings.
      Clinical and experimental evidence suggest that phytoestrogens could be used to
      ameliorate these alterations associated with menopause. However, the
      phytoestrogen effects on anxiety in rats with long-term absence of ovarian
      hormones, is unknown. Consequently, in the present study the authors compared the
      anxiolytic-like effect of phytoestrogen genistein (0.25, 0.5 y 1.0 mg/kg, i.p.)
      in Wistar rats with 12-weeks postovariectomy in the black and white model and in
      the open field test, and it was compared with diazepam (1.0 mg/kg, i.p.). In the
      black and white model, genistein (0.5 y 1.0 mg/kg) and diazepam reduced the
      latency to enter and increased the time spent into the white compartment; also,
      significantly increased frequency and time spent in exploration toward white
      compartment was seen, as compared with the control group (p<0.05). In the open
      field test, genistein and diazepam increased grooming and rearing, without
      significant changes in locomotor activity, as compared with the control group. In
      conclusion, phytoestrogen genistein produces an anxiolytic-like effect in Wistar
      rats with long-term absence of ovarian hormones in the black and white model,
      supporting the hypotheses that phytoestrogens could be used to ameliorate anxiety
      associated with menopause.

PMID- 19168114
TI  - Antioxidant and anti-quorum sensing activities of green pod of Acacia nilotica L.
AB  - The antioxidant and anti-quorum sensing activities of eight extracts were studied
      in green pods of Acacia nilotica. The specific phenolic compositions and their
      quantifications were performed by HPLC and MS/MS, which showed that the HEF (pH
      4) was higher in gallic acid, ellagic acid, epicatechin, rutin, and GTs. In order
      to find antioxidant potential of various extracts, their activities were studied
      for TPC, AOA, FRSA, RP, inhibition of LPO, FIC activity, HO* and O(2)(-)
      scavenging activities. Among them HEF (pH 4) has shown potent antioxidant
      activity. HEF (pH 4) was also found effective in protecting plasmid DNA and HAS
      protein oxidation induced by HO*. Pre-treatment of HEF (pH 4) at 75 and 150 mg/kg
      body weight for 6 days caused a significant increase in the levels of CAT and SOD
      and decrease in the level of MDA content in liver, lungs, kidneys and blood when
      compared to CCl(4)-intoxicated rats. Eventually, the extracts were also screened
      for anti-QS activity. Of these extracts two showed QS inhibition: HEF (pH 4) and
      HCE. The results obtained strongly indicate that green pod of A. nilotica are
      important source of natural antioxidants.

PMID- 19168115
TI  - Role of Panax ginseng as an antioxidant after cadmium-induced hepatic injuries.
AB  - Liver, being primary site for biotransformation of foreign compounds is
      vulnerable to various chemical assaults. Ginseng has a wide range of
      pharmacological and therapeutical action. In the present study an attempt has
      been made to study the cadmium chloride (CdCl(2)) induced toxicity in liver and
      its possible protection by Panax ginseng. Swiss albino mice were divided into
      four groups: (i) Control group--only vehicle (double distilled water) (ii)
      Ginseng treated group - 10mg/kg b.wt. orally (iii) CdCl(2) treated group -
      1.0mg/kg b.wt. CdCl(2) i.p. (iv) Combination group--Ginseng root extract (10mg/kg
      b.wt.) and CdCl(2) (1.0mg/kg b.wt.). Activities of alkaline phosphatase, GOT, GPT
      were measured in serum and lipid peroxidation (LPO) and GSH content were measured
      in liver. The results indicated a significant increase in LPO, GOT, GPT
      activities and decrease in GSH and serum alkaline phosphatase activities after
      CdCl(2) treatment. Ginseng alone did not show any significant alterations except
      a significant decrease in LPO level. Combined treatment of Ginseng and CdCl(2)
      showed significant decrease in LPO, GOT, GPT and elevation in GSH and serum
      alkaline phosphatase as compared to CdCl(2) treated group. Thus, Ginseng is found
      to be protective against cadmium-induced hepatic injuries.

PMID- 19168116
TI  - Histone modification patterns and epigenetic codes.
AB  - The eukaryotic DNA is wrapped around histone octamers, which consist of four
      different histones, H2A, H2B, H3 and H4. The N-terminal tail of each histone is
      post-transcriptionally modified. The modification patterns constitute codes that
      regulate chromatin organisation and DNA utilization processes, including
      transcription. Recent progress in technology development has made it possible to
      perform systematic genome-wide studies of histone modifications. This helps
      immensely in deciphering the histone codes and their biological influence. In
      this review, we discuss the histone modification patterns found in genome-wide
      studies in different biological models and how they influence cell
      differentiation and carcinogenesis.

PMID- 19168117
TI  - The effects of a ketogenic diet on ATP concentrations and the number of
      hippocampal mitochondria in Aldh5a1(-/-) mice.
AB  - BACKGROUND: Succinic semialdehyde dehydrogenase (SSADH) deficiency is an inborn
      error of GABA metabolism characterized clinically by ataxia, psychomotor
      retardation and seizures. A mouse model of SSADH deficiency, the Aldh5a1(-/-)
      mouse, has been used to study the pathophysiology and treatment of this disorder.
      Recent work from our group has shown that the ketogenic diet (KD) is effective in
      normalizing the Aldh5a1(-/-) phenotype, although the mechanism of the effect
      remains unclear. METHODS: Here, we examine the effects of a KD on the number of
      hippocampal mitochondria as well as on ATP levels in hippocampus. Electron
      microscopy was performed to determine the number of mitochondria in the
      hippocampus of Aldh5a1(-/-) mice. Adenosine triphosphate (ATP) levels were
      measured in hippocampal extracts. RESULTS: Our results show that the KD increases
      the number of mitochondria in Aldh5a1(-/-) mice. We also show that Aldh5a1(-/-)
      mice have significant reductions in hippocampal ATP levels as compared to
      controls, and that the KD restores ATP in mutant mice to normal levels. GENERAL
      SIGNIFICANCE: Taken together, our data suggest that the KD's actions on brain
      mitochondria may play a role in the diet's ability to treat murine SSADH
      deficiency.

PMID- 19168118
TI  - Steroid-dependent auditory plasticity for the enhancement of acoustic
      communication: recent insights from a vocal teleost fish.
AB  - The vocal plainfin midshipman fish (Porichthys notatus) has become an excellent
      model for identifying neural mechanisms of auditory perception that may be shared
      by all vertebrates. Recent neuroethological studies of the midshipman fish have
      yielded strong evidence for the steroid-dependent modulation of hearing
      sensitivity that leads to enhanced coupling of sender and receiver in this vocal
      acoustic communication system. Previous work shows that non-reproductive females
      treated with either testosterone or 17beta-estradiol exhibit an increase in the
      degree of temporal encoding by the auditory saccular afferents to the dominant
      frequency content of male vocalizations produced during social-reproductive
      behaviors. The expanded frequency sensitivity of steroid treated females mimics
      the reproductive female's auditory phenotype and is proposed to improve the
      detection and localization of calling conspecific mates during the summer
      breeding season. This review focuses on the novel form of steroid-dependent
      auditory plasticity that is found in the adult midshipman fish and its
      association with the reproductive biology and behavior of this species. Evidence
      for midshipman reproductive-state and steroid-dependent auditory plasticity is
      reviewed and the potential mechanisms that lead to this novel form of adaptive
      plasticity are discussed.

PMID- 19168119
TI  - Chemopreventive action of Lygodium flexuosum extract in human hepatoma PLC/PRF/5
      and Hep 3B cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lygodium flexuosum (Lygodiaceae), a medicinal
      fern used in Indian traditional medicine against liver disorders. AIM OF THE
      STUDY: The rationale of the study was to examine whether the n-hexane extract
      from plant Lygodium flexuosum affects apoptosis on human hepatoma PLC/PRF/5 and
      Hep 3B cells. MATERIALS AND METHODS: Chemopreventive activity of the Lygodium
      flexuosum extract was determined by MTT assay, annexin-V FITC binding to
      phosphatidyl serine and cleavage of PARP. Subdiploid condition of cells treated
      with Lygodium flexuosum was analyzed by flow cytometry. Further, used transiently
      transfected NF-kappaB reporter in PLC/PRF/5 cells to evaluate the inhibitive
      effect of Lygodium flexuosum extract. RESULTS: Lygodium flexuosum extract
      inhibited the cell viability and induced apoptosis in hepatoma cells in a
      concentration dependent manner as evidenced by apoptotic changes such as flipping
      of phosphatidyl serine, cleavage of PARP. Cell cycle analysis showed the subG1
      apoptotic population in cells treated with higher concentrations of the extract.
      When activated with exogenous TNF-alpha in transfected hepatoma cells it was
      observed that NF-kappaB dependent gene expression was inhibited by treatment with
      Lygodium flexuosum extract in PLC/PRF/5 cells dose-dependently. CONCLUSIONS: This
      investigation suggests that the Lygodium flexuosum extract has antiproliferative
      and apoptotic activity in both cancer cells and has inhibitive role in TNF-alpha
      induced NF-kappaB activation in PLC/PRF/5 cells confirms the potential of the
      extract as a chemopreventive agent.

PMID- 19168120
TI  - Use of medicinal plants for the treatment of measles in Nigeria.
AB  - AIM OF THE STUDY: The present study was an ethnobotanical survey of three Local
      Government areas of the Ijebu area of Ogun State in southwest Nigeria for plants
      used in the treatment of measles. MATERIALS AND METHODS: Unstructured interviews
      were conducted among both urban and rural dwellers of three major groups of Ijebu
      people inhabiting the area (Ijebu North, Ijebu northeast and Ijebu Ode Local
      Governments). RESULTS: A total of 20 respondents constituted by herbalists,
      herbsellers and old people that have privileged information on the plants used in
      the treatment of measles among children were encountered during the survey.
      Twenty-three plant species belonging to 18 Angiosperm families were said to
      possess curative properties for the cure of measles among the local populace.
      Amongst the most frequently used plants are Elytraria marginata Vahl, Peperomia
      pellucida (L.) Humb., Bonpl. & Kunth, Vernonia amygdalina Del., Momordica
      charantia L., Newbouldia laevis (P. Beauv.) Seem. ex Bureau, and Ocimum
      gratissimum L. CONCLUSION: The most frequently mentioned family is Cucurbitaceae.
      The mode of preparation and recommended dosages are enumerated in this paper. The
      results of the study call for an urgent need of the introduction of a strategy
      for the conservation of indigenous medicinal plants in the area.

PMID- 19168121
TI  - Effect of Tectona grandis Linn. on dexamethasone-induced insulin resistance in
      mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The bark of Tectona grandis Linn. is
      traditionally used in the treatment of diabetes. AIM: The present study was
      undertaken to investigate the effect of ethanolic extract of bark of Tectona
      grandis Linn. (TG) in dexamethasone-induced insulin resistance in mice. MATERIALS
      AND METHODS: Mice were treated with prestandardised dose of dexamethasone for 22
      days and effect of TG at the doses of 50, 100 and 200 mg/kg, p.o. on plasma blood
      glucose level, serum triglyceride level, glucose uptake in skeletal muscle,
      levels of hepatic antioxidant enzymes (GSH, SOD, catalase and LPO), and body
      weight were observed. RESULTS: TG showed significant decrease in plasma glucose
      and serum triglyceride levels (p<0.01) at the dose of 100 and 200 mg/kg, p.o. and
      also stimulated glucose uptake in skeletal muscle. The levels of antioxidant
      enzymes GSH, SOD, and catalase were significantly increased (p<0.01) and there
      was significant decrease (p<0.01) in level of LPO. CONCLUSION: Hence it can be
      concluded that Tectona grandis may prove to be effective in the treatment of Type
      II Diabetes mellitus owing to its ability to decrease insulin resistance.

PMID- 19168122
TI  - Ethnobotanical review of the Mapuche medicinal flora: use patterns on a regional
      scale.
AB  - AIM OF THE STUDY: This paper aimed to present a quantitative review of
      information on Mapuche ethnobotany published for Argentina and Chile in the
      period 1955-2007. MATERIALS AND METHODS: Sixteen ethnobotanical articles were
      studied quantitatively by utilizing ethnobotanical indices, non-parametric and
      multivariate tests. RESULTS: A total of 505 medicinal species, 304 native (60%)
      and 196 exotic (39%) were registered. Ailments were treated with both native and
      exotic species, although native showed higher values of consensus (between
      studies) than exotic, and were more frequently used in all cases. The most common
      ailments were gastro-intestinal pains (26%). Most cures used herbs (56%). Native
      species were obtained mainly by gathering in forests and ecotones (40%), and
      exotics by gathering in anthropogenic environments (28%). Our results demonstrate
      the existence of a common, shared body of knowledge of the medicinal flora at a
      regional level, integrating ancestral knowledge with foreign knowledge
      accumulated over time. Finally, reflecting cultural erosion, modern articles
      cited significantly fewer native plants than older articles; a trend not found
      with exotic species. DISCUSSION AND CONCLUSION: The information offered can be
      used as a guide for future work on promising species for health care, and as
      background information for the development of bio-cultural conservation
      strategies.

PMID- 19168123
TI  - Monoamine oxidase inhibition by Rhodiola rosea L. roots.
AB  - AIM OF THE STUDY: Rhodiola rosea L. (Crassulaceae) is traditionally used in
      Eastern Europe and Asia to stimulate the nervous system, enhance physical and
      mental performance, treat fatigue, psychological stress and depression. In order
      to investigate the influence of Rhodiola rosea L. roots on mood disorders, three
      extracts were tested against monoamine oxidases (MAOs A and B) in a microtitre
      plate bioassay. MATERIALS AND METHODS: Methanol and water extracts gave the
      highest inhibitory activity against MAOs. Twelve compounds were then isolated by
      bioassay-guided fractionation using chromatographic methods. The structures were
      determined by 1H, 13C NMR and HR-MS. RESULTS: The methanol and water extracts
      exhibited respectively inhibitions of 92.5% and 84.3% on MAO A and 81.8% and
      88.9% on MAO B, at a concentration of 100 microg/ml. The most active compound
      (rosiridin) presented an inhibition over 80% on MAO B at a concentration of 10(
      5) M (pIC50=5.38+/-0.05). CONCLUSIONS: The present investigation demonstrates
      that Rhodiola rosea L. roots have potent anti-depressant activity by inhibiting
      MAO A and may also find application in the control of senile dementia by their
      inhibition of MAO B.

PMID- 19168124
TI  - The in vitro effects of selenomethionine on methylmercury-induced neurotoxicity.
AB  - Selenium (Se) has been reported to reduce the severity of MeHg-induced
      neurological deficits. Therefore, we investigated whether 24h. preincubation or
      50min. coincubation with selenomethionine (SeMet) was effective in reducing
      methylmercury (MeHg)-induced cytotoxicity in C6-glioma and B35-neuronal cell
      lines. As indicators of cytotoxicity, reduced glutathione (GSH), reactive oxygen
      species (ROS) and mitochondrial activity (MTT) was assessed. Measurement of GSH
      with the fluorescent indicator MCB-monochlorobimane indicated that in SeMet
      preincubated C6 cells, MeHg treatment resulted in a significant (p<0.001)
      decrease in GSH levels as compared to coincubation group. Treatment with SeMet
      did not induce any significant changes in MTT activity in either of the cell
      lines as compared to the MeHg group. However, the amount of MeHg-induced ROS was
      significantly reduced (p<0.001) after SeMet preincubation in both the cell lines.
      The intracellular Se content was measured with high resolution-inductively
      coupled plasma mass spectrometry (HR-ICPMS). In both the cell lines the
      intracellular Se levels increased after pre- and coincubation with 20 and
      50microM SeMet. However, the preincubation group exhibited increased Se content
      in both the cell lines and varied (p<0.001) from coincubation group. These
      differences in the Se content were maintained after 10microM MeHg treatment for
      50min. In C6-gliomas, the cell associated-MeHg measurements using (14)C-labeled
      MeHg indicated a significant increase (p<0.001) in MeHg content in preincubated
      cells as compared to coincubated cells. These findings provide experimental
      evidence that preincubation with SeMet increases Se content in cells and prevents
      against increased MeHg-induced ROS generation.

PMID- 19168126
TI  - Regulation of OPA1-mediated mitochondrial fusion by leucine zipper/EF-hand
      containing transmembrane protein-1 plays a role in apoptosis.
AB  - Carboxyl-terminal modulator protein (CTMP) is a tumor suppressor-like binding
      partner of Protein kinase B (PKB/Akt) that negative regulates this kinase. In the
      course of our recent work, we identified that CTMP is consistently associated
      with leucine zipper/EF-hand-containing transmembrane-1 (LETM1). Here, we report
      that adenovirus-LETM1 increased the sensitivity of HeLa cells to apoptosis,
      induced by either staurosporine or actinomycin D. As shown previously, LETM1
      localized to the inner mitochondrial membrane. Electron-microscopy analysis of
      adenovirus-LETM1 transduced cells revealed that mitochondrial cristae were
      swollen in these cells, a phenotype similar to that observed in optic atrophy
      type-1 (OPA1)-ablated cells. OPA1 cleavage was increased in LETM1-overexpressing
      cells, and this phenotype was reversed by overexpression of OPA1 variant-7, a
      cleavage resistant form of OPA1. Taken together, these data suggest that LETM1 is
      a novel binding partner for CTMP that may play an important role in mitochondrial
      fragmentation via OPA1-cleavage.

PMID- 19168125
TI  - Qualitative determination of superoxide release at both sides of the
      mitochondrial inner membrane by capillary electrophoretic analysis of the
      oxidation products of triphenylphosphonium hydroethidine.
AB  - Superoxide is released asymmetrically to both sides of the mitochondrial inner
      membrane. Because this membrane is impermeable to superoxide, two separate pools
      are formed at either side of the membrane, each with its own characteristics and
      potential biological effects. Here, we report an attomole-sensitive fast
      capillary electrophoretic method that can analyze superoxide in a single pool,
      either the matrix pool or that outside the mitochondria. The method uses
      triphenylphosphonium hydroethidine, which reacts with the superoxide in both
      pools. Centrifugation is used to separate the mitochondria (i.e., matrix
      contents) from the supernatant (i.e., products released outside the
      mitochondria). Each fraction is then analyzed by capillary electrophoresis with
      laser-induced fluorescence detection that separates and detects
      hydroxytriphenylphosphonium ethidium (OH-TPP-E+), the fluorescent superoxide
      specific product. The separation takes <3 min and the detection level is down to
      3 amol OH-TPP-E+. The method has proved to be effective at detecting superoxide
      release qualitatively in the mitochondria of 143B cells, mouse liver, and rat
      skeletal muscle, in both the presence and the absence of inhibitors. In addition,
      this study confirmed that complex I releases superoxide only toward the matrix,
      whereas complex III releases superoxide toward both sides of the mitochondrial
      inner membrane. Furthermore, treatment with menadione induces superoxide release
      toward both sides of the mitochondrial inner membrane.

PMID- 19168127
TI  - Gbeta3 forms distinct dimers with specific Ggamma subunits and preferentially
      activates the beta3 isoform of phospholipase C.
AB  - Heterotrimeric G proteins regulate multiple effectors of which some are mediated
      via the Gbetagamma dimers. There is evidence to suggest that the functions of
      Gbetagamma dimers are not shared by all possible permutations of Gbetagamma
      complexes. Here, we report our efforts in defining the formation of distinct
      Gbetagamma dimers and their functional differences in activating phospholipase
      Cbeta (PLCbeta) isoforms. Co-immunoprecipitation assays using Cos-7 cells
      transiently expressing 48 different combinations of Gbeta(1-4) and Ggamma(1-5, 7
      13) subunits showed that Gbeta(1) and Gbeta(4) could form dimers with all known
      Ggamma subunits, whereas several dimers could not be observed for Gbeta(2) and
      Gbeta(3). All Gbeta(1)gamma and Gbeta(2)gamma dimers significantly stimulated
      PLCbeta isoforms (PLCbeta(2)> or =PLCbeta(3)>PLCbeta(1)), but Gbeta(3)gamma and
      Gbeta(4)gamma dimers were poor activators of PLCbeta(1) and exhibited preference
      for PLCbeta(3) and PLCbeta(2), respectively. All Gbeta subunits revealed to date
      contain the previously identified PLCbeta(2)-interacting residues, but their
      neighboring residues in the proposed 3-D structures are different. To test if
      differences in these neighboring residues affect the interactions with PLCbeta
      isoforms, we generated several Gbeta(3) mutants by replacing one or more of these
      residues with their Gbeta(1) counterparts. One of these mutants (M120I, S140A and
      A141G triple mutant) acquired enhanced PLCbeta(2)-activating functions when co
      expressed with different Ggamma subunits, while the corresponding stimulation on
      PLCbeta(3) was not altered. Taken together, our results show that the exact
      composition of a Gbetagamma dimer can determine its selectivity for activating
      PLCbeta isoforms, and certain residues in Gbeta(3) may account for the
      preferential stimulation of PLCbeta(3) by Gbeta(3)gamma dimers.

PMID- 19168128
TI  - Licochalcone A significantly suppresses LPS signaling pathway through the
      inhibition of NF-kappaB p65 phosphorylation at serine 276.
AB  - Licorice root, Glycyrrhiza inflata, has been used as a traditional medicine for
      the treatment of bronchial asthma and inflammation; however, the mechanism of its
      anti-inflammatory activity has not been clarified. Here, we investigated the
      effect of Licochalcone A, a major component of G. inflata, on the LPS signaling
      pathway. We found that Licochalcone A remarkably inhibited LPS-induced NO
      production, and TNFalpha expression and MCP-1 expression in both RAW264.7 cells
      and primary macrophages. Furthermore, when injected with Licochalcone A prior to
      injection of LPS, the serum level of TNFalpha and MCP-1 in C57BL/6 mice was
      clearly decreased, indicating that Licochalcone A has a potent anti-inflammatory
      effect both in vitro and in vivo. Strikingly, Licochalcone A significantly
      inhibited LPS-induced NF-kappaB transcriptional activation; however, it had no
      effect on not only the phosphorylation and degradation of IkappaBalpha but also
      nuclear translocation and DNA binding activity of NF-kappaB p65. Interestingly,
      Licochalcone A markedly inhibited the phosphorylation of p65 at serine 276. As a
      result, it reduced NF-kappaB transactivation by preventing the interaction of p65
      with p300. Taken together, Licochalcone A might contribute to the potent anti
      inflammatory effect of G. inflata through the unique mechanism of NF-kappaB
      inhibition.

PMID- 19168129
TI  - Carboxy-Terminal Modulator Protein (CTMP) is a mitochondrial protein that
      sensitizes cells to apoptosis.
AB  - The Carboxy-Terminal Modulator Protein (CTMP) protein was identified as a PKB
      inhibitor that binds to its hydrophobic motif. Here, we report mitochondrial
      localization of endogenous and exogenous CTMP. CTMP exhibits a dual sub
      mitochondrial localization as a membrane-bound pool and a free pool of mature
      CTMP in the inter-membrane space. CTMP is released from the mitochondria into the
      cytosol early upon apoptosis. CTMP overexpression is associated with an increase
      in mitochondrial membrane depolarization and caspase-3 and polyADP-ribose
      polymerase (PARP) cleavage. In contrast, CTMP knock-down results in a marked
      reduction in the loss of mitochondrial membrane potential as well as a decrease
      in caspase-3 and PARP activation. Mutant CTMP retained in the mitochondria loses
      its capacity to sensitize cells to apoptosis. Thus, proper maturation of CTMP is
      essential for its pro-apoptotic function. Finally, we demonstrate that CTMP
      delays PKB phosphorylation following cell death induction, suggesting that CTMP
      regulates apoptosis via inhibition of PKB.

PMID- 19168130
TI  - Signal transduction of constitutively active protein kinase C epsilon.
AB  - The protein kinase C (PKC) family is the most prominent target of tumor-promoting
      phorbol esters. For the PKCepsilon isozyme, different intracellular localizations
      and oncogenic potential in several but not all experimental systems have been
      reported. To obtain information about PKCepsilon-signaling, we investigated the
      effects of constitutively active rat PKCepsilon (PKCepsilonA/E, alanine 159 is
      replaced by glutamic acid) in HeLa cells in a doxycycline-inducible vector. Upon
      induction of PKCepsilonA/E expression by doxycycline, the major part of
      PKCepsilonA/E was localized to the Golgi. This led (i) to phosphorylations of
      PKCepsilon(S729), Elk-1(S383), PDK1(S241) and Rb(S807/S811), (ii) to elevated
      expression of receptor of activated C kinase 2 (RACK2) after 12 h, and (iii)
      increased colony formation in soft agar, increased cell migration and invasion,
      but not to decreased doubling time. Following induction of PKCepsilonA/E
      expression by doxycycline for 24 h and additional short-term treatment with 12-O
      tetradecanoylphorbol-13-acetate (TPA), PKCepsilonA/E translocated to the plasma
      membrane and increased phosphorylation of MARCKS(S152/156). Treatment with
      doxycycline/TPA or TPA alone increased phosphorylations of Elk-1(S383),
      PDK1(S241), Rb(S807/S811), PKCdelta(T505), p38MAPK(T180/Y182), MEK1/2(S217/S221)
      and ERK2(T185/T187). MARCKS was not phosphorylated after treatment with TPA
      alone, demonstrating that in this system it is phosphorylated only by PKCepsilon
      localized to the plasma membrane but not by PKCalpha or delta, the other TPA
      responsive PKC isozymes in HeLa cells. These results demonstrate that PKCepsilon
      can induce distinctly different signaling from the Golgi and from the plasma
      membrane.

PMID- 19168131
TI  - Cyclic GMP specifically suppresses Type-Ialpha cGMP-dependent protein kinase
      expression by ubiquitination.
AB  - Type I cGMP-dependent protein kinase (PKG-I) mediates nitric oxide (NO) and
      hormone dependent smooth muscle relaxation and stimulates smooth muscle cell
      specific gene expression. Expression of PKG-I in cultured smooth muscle cells
      depends on culture conditions and is inhibited by inflammatory cytokines such as
      interleukin-I and tumor necrosis factor-alpha, which are known to stimulate Type
      II NO synthase (iNOS) expression. We report here that the suppression of PKG-I
      protein levels in smooth muscle cells is triggered by the ubiquitin/26S
      proteasome pathway. Incubation of vascular smooth muscle cells with
      phosphodiesterase-resistant cyclic GMP analogs (e.g., 8-bromo-cGMP) decreases PKG
      I protein level in a time- and concentration-dependent manner. To study this
      process, we tested the effects of 8-Br-cGMP on PKG-I protein level in Cos7 cells,
      which do not express endogenous type I PKG mRNA. 8-Br-cGMP induced the
      ubiquitination and down-regulation of PKG-Ialpha, but not PKG-Ibeta. Treatment of
      cells with the 26S proteasome inhibitor, MG-132, increased ubiquitination of PKG.
      Blocking PKG-I catalytic activity using the cell-permeant specific PKG-I
      inhibitor, DT-2, inhibited cGMP-induced PKG-I ubiquitination and down-regulation,
      suggesting that PKG catalytic activity and autophosphorylation were required for
      suppression of PKG-I level. Mutation of the known autophosphorylation sites of
      PKG-Ialpha to alanine uncovered a specific role for autophosphorylation of serine
      64 in cGMP-dependent ubiquitination and suppression of PKG-I level. The results
      suggest that chronic elevation of cGMP, as seen in inflammatory conditions,
      triggers ubiquitination and degradation of PKG-Ialpha in smooth muscle.

PMID- 19168132
TI  - Inherited glycosylphosphatidyl inositol deficiency: a treatable CDG.
AB  - Tethering to cell membrane through attachment to the complex glycolipid anchor
      glycosylphosphatidyl inositol (GPI) is a mode of protein expression highly
      conserved in eukaryotes. The evolutionary purpose of such an elaborate way of
      expressing proteins is not clear and neither is the functional role of GPI
      itself. GPI-anchored proteins (GPI-AP) serve a variety of functions that include
      adhesion, receptors, signal transduction and complement activation. GPI
      biosynthesis, a process that is accomplished in at least 9 steps and involves
      several proteins, some with enzymatic activity, would be expected to be a fertile
      ground for development of inherited, autosomal recessive disorders. However,
      until recently, paroxysmal nocturnal haemoglobinuria, a rare haematological
      disorder caused by somatic mutations in the X-linked PIGA gene, was the only
      genetic disorder affecting GPI biosynthesis. Here we review the clinical
      spectrum, biochemical defect and genetic pathogenesis of inherited GPI
      deficiency, the first described form of inherited, autosomal recessive disorder
      of GPI biosynthesis and outline the molecular basis of targeted therapy for this
      condition.

PMID- 19168133
TI  - Mendelian forms of Parkinson's disease.
AB  - Over the last few years, genetic findings have changed our views on Parkinson's
      disease (PD), as mutations in a growing number of genes are found to cause
      monogenic forms of the disorder. Point mutations in the gene for alpha-synuclein,
      as well as duplications and triplications of the wild-type gene cause a dominant
      form of PD in rare families, pointing towards mishandling of this protein as a
      crucial step in the molecular pathogenesis of the disorder. Mutations in the gene
      for leucine-rich repeat kinase 2 (LRRK2) have recently been identified as a much
      more common cause for dominant PD, while mutations in the parkin gene, in DJ-1,
      PINK1 and ATP13A2 all cause autosomal-recessive parkinsonism of early onset.
      Mutations in recessive genes probably are pathogenic through loss-of-function
      mechanisms, suggesting that their wild-type products protect dopaminergic cells
      against a variety of insults. Evidence is emerging that at least some of these
      genes may play a direct role in the etiology of the common sporadic form of PD.
      Further, it is likely that the cellular pathways identified in rare monogenic
      variants of the disease also shed light on the molecular pathogenesis in typical
      sporadic PD.

PMID- 19168134
TI  - Fenofibrate-loaded PLGA microparticles: effects on ischemic stroke.
AB  - Many drugs are not able to cross the Blood Brain Barrier (BBB) and, thus, cannot
      reach a target site within the Central Nervous System (CNS). Local controlled
      drug delivery can help to overcome this restriction. However, this is a highly
      challenging approach and only one product is yet available on the market:
      Gliadel, which is used to reduce the risk of local tumor recurrence upon
      resection of malignant glioma. The aim of this study was to evaluate the
      potential of local controlled drug delivery to the CNS to reduce the consequences
      of ischemic stroke. Fenofibrate as well as its active metabolite fenofibric acid
      were encapsulated within PLGA microparticles. Importantly, fenofibrate-loaded
      microparticles effectively reduced the consequences of ischemic stroke in Wistar
      rats: the total, cortical and striatal infarct volumes decreased from 257 to 197,
      193 to 139, and 64 to 58 mm(3), respectively. Interestingly, fenofibric acid
      loaded microparticles did not show significant in vivo efficacy, which might be
      attributable to a potentially limited distribution pattern within the brain
      and/or limited cell uptake. Thus, local controlled drug delivery to the CNS also
      has a significant potential for the treatment/prevention of other types of
      diseases than cancer. Furthermore, this approach can help to provide proof of
      concept in vivo in the early drug discovery phase, if the drug candidate cannot
      cross the BBB.

PMID- 19168135
TI  - Cuticle laccase of the silkworm, Bombyx mori: purification, gene identification
      and presence of its inactive precursor in the cuticle.
AB  - Laccase is a multi-copper enzyme found in variety of organisms including plants,
      fungi and bacteria. In insects, laccase is thought to play an important role in
      cuticle sclerotization with its ability to catalyze the oxidation of phenolic
      compounds to their corresponding quinones. From the newly ecdysed pupae of the
      silkworm, Bombyx mori, we purified a dimer form of cuticular laccase with 70-kDa
      polypeptides. Mass spectrometric analysis of the tryptic fragments and cDNA
      sequence analysis revealed that the gene for the purified laccase (BmLaccase2) is
      an ortholog of laccase2, one of the multiple laccase genes found in insect
      genomes. BmLaccase2 is highly expressed in the epidermis prior to ecdysis,
      suggesting that the BmLaccase2 protein accumulates before ecdysis. However, the
      cuticle of newly ecdysed pupa does not have laccase activity, and the activity
      only becomes detectable several hours after ecdysis. These data suggest that
      cuticle laccase is synthesized as an inactive precursor, which is later activated
      after ecdysis. We also found that urea-solubilized cuticle protein extract
      contains an inactive form of laccase that can be activated by trypsin treatment.

PMID- 19168136
TI  - Glutamate toxicity in the striatum of the R6/2 Huntington's disease transgenic
      mice is age-dependent and correlates with decreased levels of glutamate
      transporters.
AB  - Glutamate excitotoxicity has been implicated in the neuropathology of
      Huntington's disease (HD), due to the toxicity of glutamate receptor agonists on
      striatal medium spiny neurons (MSN), the most affected neuronal population in HD.
      Previous studies showed functional alterations of NMDA glutamate receptors and
      decreased expression of glutamate transporters in transgenic models and HD
      patients, suggesting the presence of excitotoxic damage. We have studied the
      vulnerability of the striatum to glutamate toxicity in R6/2 mice at 10 and 14
      weeks of age. At 10 weeks R6/2 and wild-type mice are equally vulnerable to
      glutamate toxicity, while at 14 weeks transgenic mice show increased damage, as
      assessed by Nissl and Fluoro Jade staining. In addition, increased electrical
      brain activity is observed after glutamate administration in transgenic mice, as
      monitored electroencephalographically. According to western blot analysis,
      increased vulnerability to glutamate toxicity correlates with decreased levels of
      GLT-1 and GLAST glutamate transporters in the striatum.

PMID- 19168137
TI  - Transcription factor RBP-J-mediated signaling represses the differentiation of
      neural stem cells into intermediate neural progenitors.
AB  - Notch signaling is critical for multiple aspects of neurogenesis, but how it
      regulates the proliferation and differentiation of neural stem cells (NSCs) and
      intermediate neural progenitors (INPs) has not been well elucidated, especially
      in vivo. In this study, we conditionally ablated the transcription factor RBP-J,
      which mediates signaling from all four mammalian Notch receptors, in the basal
      forebrain and ventral midbrain using the RBP-J-floxed mouse and a newly
      established Nestin-Cre mouse. We found that at early stage of neurogenesis
      (E11.5), the frequency of neurospheres increased significantly in the RBP-J
      inactivated regions. The majority of the RBP-J deficient neurospheres were
      composed of INPs, suggesting the precocious differentiation of NSCs into INPs.
      Meanwhile, neuronal differentiation was reduced in the same regions at E11.5,
      inconsistent with the precocious differentiation phenotype in most Notch-related
      mutants. At late neurogenic stages (E17.5 and neonatal), as expected from
      precociously exhausted NSC pool, neurosphere frequency and NSCs decreased in the
      RBP-J-ablated regions, accompanied by a significant increase of both neurons and
      glial cells. These results indicated that the RBP-J-mediated signaling might
      inhibit the differentiation of NSCs into INPs and support the generation of
      certain early born neurons at early neurogenic stages.

PMID- 19168138
TI  - Reduced volume of Heschl's gyrus in tinnitus.
AB  - The neural basis of tinnitus is unknown. Recent neuroimaging studies point
      towards involvement of several cortical and subcortical regions. Here we
      demonstrate that tinnitus may be associated with structural changes in the
      auditory cortex. Using individual morphological segmentation, the medial
      partition of Heschl's gyrus (mHG) was studied in individuals with and without
      chronic tinnitus using magnetic resonance imaging. Both the tinnitus and the non
      tinnitus group included musicians and non-musicians. Patients exhibited
      significantly smaller mHG gray matter volumes than controls. In unilateral
      tinnitus, this effect was almost exclusively seen in the hemisphere ipsilateral
      to the affected ear. In bilateral tinnitus, mHG volume was substantially reduced
      in both hemispheres. The tinnitus-related volume reduction was found across the
      full extent of mHG, not only in the high-frequency part usually most affected by
      hearing loss-induced deafferentation. However, there was also evidence for a
      relationship between volume reduction and hearing loss. Correlations between
      volume and hearing level depended on the subject group as well as the asymmetry
      of the hearing loss. The volume changes observed may represent antecedents or
      consequences of tinnitus and tinnitus-associated hearing loss and also raise the
      possibility that small cortical volume constitutes a vulnerability factor.

PMID- 19168139
TI  - Age and diffusion tensor anisotropy in adolescent and adult patients with
      schizophrenia.
AB  - Findings of white matter pathology as indicated by diffusion tensor anisotropy
      values in schizophrenia are well established, but the differences in this measure
      between the onset of the disease and the chronic state are not well known. To
      investigate the differences between these states in the progression of the
      disease of schizophrenia we acquired 1.5 T diffusion tensor anisotropy images on
      35 adult patients with schizophrenia and schizoaffective disorder, 23 adolescents
      having their first psychotic episode, and age and sex matched controls (33 adults
      and 15 adolescents). Regions of interest in major cortical white matter tracts
      chosen as salient to the prefrontal executive deficit in schizophrenia were
      assessed using stereotaxic coordinates from the Talairach and Tournoux atlas.
      Regions of each tract along anterior-posterior and/or inferior-superior
      directions in both hemispheres were evaluated in multiway ANOVA. Tracts between
      the frontal lobe and other brain regions, but not temporal, occipital and
      interhemispheric tracts, showed a differential aging pattern in normals and
      patients indicating that the white matter pathology in these regions is not
      stable between the onset and the chronic state in schizophrenia. This suggests
      that tracts involved in the connectivity of the temporal lobe white matter
      deficits were already well in place in adolescent patients, while frontal lobe
      pathology continues to develop from adolescence to adulthood.

PMID- 19168140
TI  - Phylogeny of the Neotropical genus Acestrorhynchus (Ostariophysi: Characiformes)
      based on nuclear and mitochondrial gene sequences and morphology: a total
      evidence approach.
AB  - Acestrorhynchus is the sole genus of the family Acestrorhynchidae which includes
      14 species currently recognized as valid. Species of Acestrorhynchus comprise
      small-to-medium sized piscivorous fishes and have been traditionally grouped on
      the basis of well-defined color patterns. A recent phylogeny, based on
      morphological characters, could not resolve the phylogenetic affinities of A.
      heterolepis and the relationships among the species of the clade formed by A.
      abbreviatus, A. altus, A. falcatus, A. lacustris, and A. pantaneiro. The
      simultaneous analysis of two mitochondrial genes (16S and ATP synthase subunits 6
      and 8) and one nuclear intron (S7) was able to resolve the latter clade, but the
      position of A. heterolepis remained unresolved. The combination of the molecular
      and morphological data sets in a total evidence analysis resulted in a well
      resolved hypothesis regarding the phylogenetic relationships of Acestrorhynchus
      species.

PMID- 19168142
TI  - Honoring a friend: Brutality ends career of a young Brazilian scientist.

PMID- 19168141
TI  - Behavioral memory induced by stimulation of the nucleus basalis: effects of
      contingency reversal.
AB  - Specific behavioral associative memory induced by stimulation of the cortically
      projecting cholinergic nucleus basalis (NB) is dependent on intrinsic
      acetylcholine and shares with natural memory such features as associativity,
      specificity, rapid formation, consolidation and long-term retention. Herein, we
      examined extinction and the effects of stimulus pre-exposure. Two groups of adult
      male rats (n=4 each) were first tested for behavioral responses (disruption of
      ongoing respiration) to tones (1-15 kHz), constituting a pre-training behavioral
      frequency generalization gradient (BFGG). They next received a first session of
      training, 200 trials of a tone (8.00 kHz, 70 dB, 2 s) either paired with
      electrical stimulation of the NB (100 Hz, 0.2 s, approximately 67 microA, NBstm)
      (group IP) or unpaired (group IU). Twenty-four hours later, they were tested for
      behavioral memory by obtaining post-training BFGGs. Then the contingencies were
      reversed yet another 24 h later; the IP group received tone and NBstm unpaired
      and the IU group received them paired. A final set of generalization gradients
      was obtained the next day. All stimuli were presented with subjects under state
      control indexed by regular respiration. Tested 24 h post-initial training, the IP
      group developed specific associative behavioral memory indicated by increased
      responses only to CS-band frequencies, while the IU group did not. After
      subsequent training with unpaired stimuli, the IP group exhibited experimental
      extinction. Furthermore, after initial exposure to the CS and NBstm unpaired, the
      IU group exhibited a tendency toward reduced conditioning to CS/NBstm pairing and
      a significant increase in latency of conditioned responses. The present findings
      provide additional support for the hypothesis that engagement of the NB is
      sufficient to induce natural associative memory and suggest that activation of
      the NB may be a normal component in the formation of natural associative memory.

PMID- 19168143
TI  - The zebrafish as a model system for glucocorticoid receptor research.
AB  - Glucocorticoids regulate a plethora of physiological processes, and are widely
      used clinically as anti-inflammatory drugs. Their effects are mediated by the
      glucocorticoid receptor (GR), a ligand-activated transcription factor. Currently,
      zebrafish embryos are being developed into a model system for GR research, since
      they are easy to manipulate genetically and their phenotype can easily be
      visualized because of their transparent bodies. In addition, the zebrafish GR
      gene shows a relatively high level of similarity with its human equivalent.
      First, both the zebrafish and the human genome contain only a single gene
      encoding the GR. In all other fish species studied thus far, two GR genes have
      been found. Second, the zebrafish contains a C-terminal GR splice variant with
      high similarity to the human GRbeta, which has been shown to be a dominant
      negative inhibitor of the canonical GRalpha and may be involved in glucocorticoid
      resistance. Thus, zebrafish embryos are potentially a useful model system for
      glucocorticoid receptor research, but currently only a limited number of tools is
      available. In this review, we discuss which tools are available and which need to
      be developed, in order to exploit the full potential of the zebrafish as a model
      system for GR research.

PMID- 19168144
TI  - Characterization of arylalkylamine N-acetyltransferase (AANAT) activities and
      action spectrum for suppression in the band-legged cricket, Dianemobius
      nigrofasciatus (Orthoptera: Gryllidae).
AB  - Arylalkylamine N-acetyltransferase (AANAT), constituting a large family of
      enzymes, catalyzes the transacetylation from acetyl-CoA to monoamine substrates,
      although homology among species is not very high. AANAT in vertebrates is
      photosensitive and mediates circadian regulation. Here, we analyzed AANAT of the
      cricket, Dianemobius nigrofasciatus. The central nervous system contained AANAT
      activity. The optimum pHs were 6.0 (a minor peak) and 10.5 (a major peak) with
      crude enzyme solution. We analyzed the kinetics at pH 10.5 using the sample
      containing collective AANAT activities, which we term AANAT. Lineweaver-Burk plot
      and secondary plot yielded a K(m) for tryptamine as substrate of 0.42 microM, and
      a V(max) of 9.39 nmol/mg protein/min. The apparent K(m) for acetyl-CoA was 59.9
      microM and the V(max) was 8.14 nmol/mg protein/min. AANAT of D. nigrofasciatus
      was light-sensitive. The activity was higher at night-time than at day-time as in
      vertebrates. To investigate most effective wavelengths on AANAT activity, a
      series of monochromatic lights was applied (350, 400, 450, 500, 550, 600 and 650
      nm). AANAT showed the highest sensitivity to around 450 nm and 550 nm. 450 nm
      light was more effective than 550 nm light. Therefore, the most effective light
      affecting AANAT activity is blue light, which corresponds to the absorption
      spectrum of blue wave (BW)-opsin.

PMID- 19168146
TI  - The salmonid cathelicidins: a gene family with highly varied C-terminal
      antimicrobial domains.
AB  - The cathelicidin family of host defence peptides is regarded as an important
      component of the host innate immune system. Its members have been found in
      mammals, birds, primitive vertebrate Atlantic hagfish and, most recently, also in
      ray-finned fish such as rainbow trout and Atlantic salmon. By using genomic PCR
      amplifications and RT-PCR tissue analyses we have here investigated and
      characterized the cathelicidin gene family in three salmonids: brown trout (Salmo
      trutta fario), brook trout (Salvelinus fontinalis) and grayling (Thymallus
      thymallus). One or two different genes were found in each species coding for
      almost identical cathelin-like domains and largely varied cationic C-terminal
      regions. Multiple alignment of the amino acid sequences let us recognize two
      distinctive hallmarks of these peptides: the presence of a high number of serine
      and glycine residues, which may collocate them in a new class of antimicrobial
      peptides, and of the six-amino-acid repeated sequence RPGGGS detected in a
      variable number of copies among different cathelicidins. The high variation in
      length and sequence of this region suggests the existence of a genetically
      unstable region similar to that found in some mammalian cathelicidins.

PMID- 19168145
TI  - Iron loaded ferritin secretion and inhibition by CI-976 in Aedes aegypti larval
      cells.
AB  - Ferritin is a multimer of 24 subunits of heavy and light chains. In mammals, iron
      taken into cells is stored in ferritin or incorporated into iron-containing
      proteins. Very little ferritin is found circulating in mammalian serum; most is
      retained in the cytoplasm. Female mosquitoes, such as Aedes aegypti (yellow fever
      mosquito, Diptera), require a blood meal for oogenesis. Mosquitoes receive a
      potentially toxic level of iron in the blood meal which must be processed and
      stored. We demonstrate by (59)Fe pulse-chase experiments that cultured A. aegypti
      larval CCL-125 cells take up iron from culture media and store it in ferritin
      found mainly in the membrane fraction and secrete iron-loaded ferritin. We
      observe that in these larval cells ferritin co-localizes with ceramide-containing
      membranes in the absence of iron. With iron treatment, ferritin is found
      associated with ceramide-containing membranes as well as in cytoplasmic non
      ceramide vesicles. Treatment of CCL-125 cells with iron and CI-976, an inhibitor
      of lysophospholipid acyl transferases, disrupts ferritin secretion with a
      concomitant decrease in cell viability. Interfering with ferritin secretion may
      limit the ability of mosquitoes to adjust to the high iron load of the blood meal
      and decrease iron delivery to the ovaries reducing egg numbers.

PMID- 19168147
TI  - Milk composition of captive vervet monkey (Chlorocebus pygerythrus) and rhesus
      macaque (Macaca mulatta) with observations on gorilla (Gorilla gorilla gorilla)
      and white handed gibbon (Hylobates lar).
AB  - The nutrient content and fatty acid composition of vervet monkey milk has been
      determined and is compared with rhesus macaque, and two hominoid apes, the white
      handed gibbon and gorilla. With 15.7+/-4.1 g protein, 33.1+/-9.4 g fat, and
      85.1+/-7.5 g lactose per kg milk, vervet monkey milk does not differ from that of
      rhesus macaque, and is within the range of other primates. Small amounts (>1 g
      kg(-1)) of oligosaccharides, glucose, galactose and fucose were noted. In
      comparison, gorilla milk has a low fat content of 13.8 g kg(-1), but contains
      high levels of oligosaccharides at 7.0 g kg(-1) milk. The hominoid partner, the
      white handed gibbon, contains no oligosaccharides and a milk fat content similar
      to other hominoid species. Differences between vervet monkey and rhesus macaque
      milks were observed in the electrophoretic pattern of the milk proteins, mainly
      amongst the kappa- and gamma-caseins, which also differ from that of the
      hominids. The fatty acid contents of these milks differ from studies where a
      natural diet of leafy material was available in that a low content of alpha
      linolenic acid (18:3n-3) was noted. A phylogenetic effect is observed for the
      content of 8:0, 10:0 fatty acids between the Cercopithecidae and Hominoidea, and
      a further phylogenetic effect suggested between the Hylobatidae and Hominidae.

PMID- 19168148
TI  - Identification of nuclear localization and nuclear export signals in Ets2, and
      the transcriptional regulation of Ets2 and CTP:phosphocholine
      cytidylyltransferase alpha in tetradecanoyl-13-acetate or macrophage-colony
      stimulating factor stimulated RAW264 cells.
AB  - PC is made via the CDP-choline pathway, in which CTP:phosphocholine
      cytidylyltransferase alpha (CTalpha), encoded by Pcyt1a, is the rate-limiting
      enzyme whose mRNA expression is strictly regulated. Previously, we reported that
      Ets1 enhanced and Net repressed CTalpha transcription by binding at the Ets
      binding site (-49/-47) in the Pcyt1a promoter. In this study, we asked if an Ets1
      analogue, Ets2, also regulates CTalpha transcription and investigated the
      importance of its nuclear localization signal (NLS) and nuclear export signal
      (NES). Ets2 is primarily detected in the nucleus. Various mutated Ets2 proteins
      fused with enhanced green fluorescent protein were constructed to identify the
      NLS and NES in Ets2. Mutation of Ets2 at amino acids 404-410 results in a protein
      that is evenly distributed in the cell. Interestingly, an Ets2 protein deleted at
      the C-terminus (amino acids 1-392 present) was localized to the cytoplasm and
      site-specific mutation in the region 364-372 of this construct resulted in
      cytoplasmic and nuclear distribution. These results suggest that the NLS in Ets2
      is between amino acids 404 and 410, and that the NES is between amino acids 364
      and 372. Ets2 enhanced, but the mutant forms of Ets2 had little effects on the
      transcription of a CTalpha-reporter construct. When RAW264 cells, murine
      macrophage cell-line, were stimulated with 12-O-tetradecanoylphorbol-13-acetate
      (TPA) or macrophage-colony stimulating factor, the transcription of CTalpha was
      enhanced accompanied by increased mRNA of Ets2. These results suggest that the
      induction of Ets2 is important for CTalpha transcription by TPA and macrophage
      colony stimulating factor.

PMID- 19168150
TI  - Effect of plasma triglyceride metabolism on lipid storage in adipose tissue:
      studies using genetically engineered mouse models.
AB  - The obesity epidemic is associated with an increased incidence of type 2
      diabetes, cardiovascular morbidity and various types of cancer. A better insight
      into the molecular mechanisms that underlie adipogenesis and obesity may result
      in novel therapeutic handles to fight obesity and these associated diseases.
      Adipogenesis is determined by the balance between uptake of fatty acids (FA) from
      plasma into adipocytes, intracellular FA oxidation versus esterification of FA
      into triglycerides (TG), lipolysis of TG by intracellular lipases, and secretion
      of FA from adipocytes. Here, we review the mechanisms that are specifically
      involved in the entry of FA into adipose tissue. In plasma, these originating FA
      are either present as TG within apoB-containing lipoproteins (i.e. chylomicrons
      and VLDL) or as free FA bound to albumin. Kinetic studies, however, have revealed
      that TG are the major source of FA entering adipose tissue, both in the fed and
      fasted condition. In fact, studies with genetically engineered mice have revealed
      that the activity of lipoprotein lipase (LPL) is a major determinant for the
      development of obesity. As a general rule, high fat diet-induced adipogenesis is
      aggravated by stimulated LPL activity (e.g. by adipose tissue-specific
      overexpression of LPL or deficiency for apoCIII), and attenuated by inhibited LPL
      activity (e.g. by adipose-specific deficiency for LPL, overexpression of apoCI or
      angptl4, or by deficiency for apoE or the VLDL receptor). In addition, we
      describe that the trans-membrane transport of FA and cytoplasmic binding of FA in
      adipocytes can also dramatically affect adipogenesis. The relevance of these
      findings for human pathophysiology is discussed.

PMID- 19168149
TI  - C. elegans fat storage and metabolic regulation.
AB  - C. elegans has long been used as an experimentally tractable organism for
      discovery of fundamental mechanisms that underlie metazoan cellular function,
      development, neurobiology, and behavior. C. elegans has more recently been
      exploited to study the interplay of environment and genetics on lipid storage
      pathways. As an experimental platform, C. elegans is amenable to an extensive
      array of forward and reverse genetic, a variety of "omics" and anatomical
      approaches that together allow dissection of complex physiological pathways. This
      is particularly relevant to the study of fat biology, as energy balance is
      ultimately an organismal process that involves behavior, nutrient digestion,
      uptake and transport, as well as a variety of cellular activities that determine
      the balance between lipid storage and utilization. C. elegans offers the
      opportunity to dissect these pathways and various cellular and organismal
      homeostatic mechanisms in the context of a genetically tractable, intact
      organism.

PMID- 19168151
TI  - Lipid analysis of mitochondrial membranes from the yeast Pichia pastoris.
AB  - Here we describe for the first time isolation and biochemical characterization of
      highly purified mitochondrial inner and outer membranes from Pichia pastoris and
      systematic lipid analysis of submitochondrial fractions. Mitochondria of this
      yeast are best developed during growth on glycerol or sorbitol, but also on
      methanol or fatty acids. To obtain organelle membranes at high quality, methods
      of isolation and subfractionation of mitochondria originally developed for
      Saccharomyces cerevisiae were adapted and employed. A characteristic feature of
      the outer mitochondrial membrane of P. pastoris is the higher phospholipid to
      protein ratio and the lower ergosterol to phospholipid ratio compared to the
      inner membrane. Another marked difference between the two mitochondrial membranes
      is the phospholipid composition. Phosphatidylcholine and phosphatidylethanolamine
      are major phospholipids of both membranes, but the inner membrane is enriched in
      cardiolipin, whereas the outer membrane contains a high amount of
      phosphatidylinositol. The fatty acid composition of both mitochondrial membranes
      is similar. Variation of the carbon source, however, leads to marked changes of
      the fatty acid pattern both in total and mitochondrial membranes. In summary, our
      data are the first step to understand the P. pastoris lipidome which will be
      prerequisite to manipulate membrane components of this yeast for biotechnological
      purposes.

PMID- 19168152
TI  - A pseudo-phytochelatin synthase in the ciliated protozoan Tetrahymena
      thermophila.
AB  - Phytochelatins (PCs) and metallothioneins (MTs) are the two major heavy metal
      chelating peptides in eukaryotes. We report here on the identification of a
      biosynthetically inactive pseudo-phytochelatin synthase enzyme (TtpsiPCS) in the
      ciliate Tetrahymena thermophila, the first of this kind (pseudo-PCS) to be
      described in eukaryotes. TtpsiPCS which resembles a true PCS at the N-terminal
      region, while it is most divergent in its Cys-poor C-terminal region, was found
      to be up-regulated under cadmium stress conditions. However, only glutathione
      (GSH) hydrolysis products, but not PCs, could be detected in extracts from Cd
      treated cells. The latter feature is reminiscent of pseudo-PCS enzymes recently
      identified in cyanobacteria, which are also biosynthetically inactive, but
      capable to hydrolyze GSH.

PMID- 19168153
TI  - Alcohol use and cigarette smoking as risk factors for post-endoscopic retrograde
      cholangiopancreatography pancreatitis.
AB  - BACKGROUND & AIMS: Alcohol use and cigarette smoking are associated with various
      pancreatic diseases, but it is not known whether they associate with post
      endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). We
      performed a retrospective case-control study to determine if these activities
      increase the risk of PEP. METHODS: We identified 7638 patients who had undergone
      ERCP in the University of Michigan Health System and applied exclusion criteria
      to identify 123 with PEP. We randomly selected 308 age- and sex-stratified
      controls (2.5-fold case sample); after applying exclusion criteria 248 remained.
      In a masked fashion, we collected data for alcohol use, cigarette smoking, and 5
      internal control variables: suspected sphincter of Oddi dysfunction (SOD),
      pancreatic sphincterotomy, moderate/difficult cannulation, 2 or more pancreatic
      injections, and pancreatic stent placement. RESULTS: The univariate model showed
      an increased frequency of PEP in current drinkers (P < .001), former drinkers (P
      < .001), and former smokers (P < .001), as well as patients who were suspected of
      having SOD (P < .001), had undergone pancreatic sphincterotomy (P < .001), had a
      moderate/difficult cannulation (P = .001), and/or had 2 or more pancreatic
      injections (P = .007). The frequency of PEP was reduced in current smokers (P <
      .001). The multivariate model showed that the only independent significant
      predictors of PEP were current drinking (odds ratio [OR], 4.70; 95% confidence
      interval [CI], 2.60-8.50; P < .0001), former cigarette smoking (OR, 3.29; 95% CI,
      1.28-8.44; P < .013), suspected SOD (OR, 3.69; 95% CI, 1.94-7.02; P < .001), and
      pancreatic sphincterotomy (OR, 5.91; 95% CI, 2.04-17.14; P = .001). CONCLUSIONS:
      Current alcohol use and potentially former cigarette smoking are new risk factors
      for PEP. It is important to consider these variables in designing PEP prevention
      trials.

PMID- 19168154
TI  - Clinical evaluation of endoscopic trimodal imaging for the detection and
      differentiation of colonic polyps.
AB  - BACKGROUND & AIMS: Endoscopic trimodal imaging (ETMI) incorporates high
      resolution endoscopy (HRE) and autofluorescence imaging (AFI) for adenoma
      detection, and narrow-band imaging (NBI) for differentiation of adenomas from
      nonneoplastic polyps. The aim of this study was to compare AFI with HRE for
      adenoma detection and to assess the diagnostic accuracy of NBI for
      differentiation of polyps. This was a randomized trial of tandem colonoscopies.
      The study was performed at the Academic Medical Center in Amsterdam. METHODS: One
      hundred patients underwent colonoscopy with ETMI. Each colonic segment was
      examined twice for polyps, once with HRE and once with AFI, in random order per
      patient. All detected polyps were assessed with NBI for pit pattern and with AFI
      for color, and subsequently removed. Histopathology served as the gold standard
      for diagnosis. The main outcome measures of this study were adenoma miss-rates of
      AFI and HRE, and diagnostic accuracy of NBI and AFI for differentiating adenomas
      from nonneoplastic polyps. RESULTS: Among 50 patients examined with AFI first, 32
      adenomas were detected initially. Subsequent inspection with HRE identified 8
      additional adenomas. Among 50 patients examined with HRE first, 35 adenomas were
      detected initially. Successive AFI yielded 14 additional adenomas. The adenoma
      miss-rates of AFI and HRE therefore were 20% and 29%, respectively (P = .351).
      The sensitivity, specificity, and overall accuracy of NBI for differentiation
      were 90%, 70%, and 79%, respectively; corresponding figures for AFI were 99%,
      35%, and 63%, respectively. CONCLUSIONS: The overall adenoma miss-rate was 25%;
      AFI did not significantly reduce the adenoma miss-rate compared with HRE. Both
      NBI and AFI had a disappointing diagnostic accuracy for polyp differentiation,
      although AFI had a high sensitivity.

PMID- 19168155
TI  - Depot-specific alterations to insulin signaling in mesenteric adipose tissue
      during intestinal inflammatory response.
AB  - Current knowledge suggests that adipose tissue is an active organ, participating
      in intestinal and mesenteric disease. Additionally, adipose tissue surrounds the
      lymph nodes and has special properties, acting as a paracrine regulator of
      adjacent lymphoid tissues. These adipose tissue depots can express and secrete
      numerous cytokines, known as adipocytokines, which then modify the action of
      insulin in adipose tissue itself. Using a well-accepted model of intestinal
      inflammation, we studied insulin signaling in mesenteric adipose tissue (MAT) and
      in perinodal mesenteric adipose tissue (PAT). Our results showed that the action
      of insulin is modified during the intestinal inflammatory response in these
      adipose tissue depots. MAT became resistant to insulin signaling, as evaluated by
      the IRS/AKT pathway, in the inflammation. This resistant status was associated
      with high JNK activity and the presence of infiltrating macrophages. Conversely,
      the adipose tissue that involves the mesenteric lymph nodes acquired greater
      sensitivity to insulin signaling via IRS/AKT, probably via up-regulation of IRS
      during experimental colitis. We demonstrated experimentally the existence of site
      specific adaptive alterations in two mesenteric adipose tissue depots to the
      intestinal inflammatory response, probably resulting in alterations in free fatty
      acids and other secretory products supplied by the adjacent tissues that could
      act as inflammatory modulator substances.

PMID- 19168156
TI  - Inhibitory effects of ivermectin on nitric oxide and prostaglandin E2 production
      in LPS-stimulated RAW 264.7 macrophages.
AB  - We have previously shown that ivermectin inhibits LPS-induced production of
      inflammatory cytokines. In the present study, we investigated the effect of
      ivermectin on lipopolysaccharide (LPS)-induced nitric oxide (NO) and
      prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages. Ivermectin
      inhibited LPS-induced NO and PGE(2) production. Consistent with these
      observations, the protein and mRNA expression levels of inducible nitric oxide
      synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes were inhibited by ivermectin
      in a concentration-dependent manner. Furthermore, the phosphorylation of p38,
      ERK1/2, and JNK in LPS-stimulated RAW 264.7 cells was suppressed by ivermectin in
      a dose-dependent manner. These results suggest that ivermectin suppresses NO and
      PGE(2) production, as well as iNOS and COX-2 expression, by inhibiting
      phosphorylation of mitogen-activated protein kinases (MAPK) (p38, ERK1/2, and
      JNK) in LPS-stimulated RAW 264.7 cells.

PMID- 19168157
TI  - Autoantibody targets and their cancer relationship in the pathogenicity of
      paraneoplastic retinopathy.
AB  - Paraneoplastic retinopathies (PR), including cancer-associated retinopathy (CAR)
      or the closely related melanoma-associated retinopathy (MAR) occur in a small
      subset of patients with retinal degeneration and systemic cancer. This autoimmune
      syndrome is characterized by sudden, progressive loss of vision in association
      with circulating anti-retinal autoantibodies. The PR syndromes are heterogeneous,
      may produce a number of ocular symptoms, and may be associated with several
      different neoplasms, including lung, breast, prostate, gynecological, and colon
      cancer, melanoma, and hematologic malignancies. We examined the onset of
      retinopathy in correlation to the diagnosis of cancer and the presence of
      specific anti-retinal autoantibodies in PR patients. In some patients without
      diagnosed malignant tumors, the onset of ocular symptoms and the presence of
      autoantibodies preceded the diagnosis of cancer by months to years, including
      anti-recoverin, anti-transducin-alpha, and anti-carbonic anhydrase II antibodies.
      Although anti-retinal autoantibodies may not be a good predictor of a specific
      neoplasm, they can be used as biomarkers for different subtypes of retinopathy.
      Identification of autoantibodies involved in autoimmune-mediated PR will help
      elucidate the mechanisms underlying the PR syndromes and develop targeted
      therapies for these sight-threatening disorders.

PMID- 19168158
TI  - Metabolic syndrome in rheumatological diseases.
AB  - Metabolic syndrome is characterized by a combination of various cardiovascular
      risk factors (age, gender, smoking, hypertension and dyslipidemia) that imply
      additional cardiovascular morbidity that is greater than the sum of the risks
      associated with each individual component. Herein, the authors review the
      rheumatological diseases in which metabolic syndrome has been studied: gout,
      osteoarthritis, systemic lupus erythematosus, rheumatoid arthritis, Sjogren's
      syndrome and ankylosing spondylitis. The prevalence of metabolic syndrome in
      these disorders varies from 14% to 62.8%. The great majority of these studies
      demonstrated that this frequency was higher in rheumatological diseases than in
      the control populations, suggesting that either the presence or the treatment of
      those diseases seems to influence the risk of developing metabolic syndrome.

PMID- 19168159
TI  - Differential proteomic analysis of HT29 Cl.16E and intestinal epithelial cells by
      LC ESI/QTOF mass spectrometry.
AB  - Intestinal epithelial cells (IECs) play a key role in Crohn's disease, a chronic
      inflammatory bowel disease which requires invasive examinations to be diagnosed.
      The comparison of the cellular protein expression profiles of Crohn's disease
      patients and healthy subjects is fundamental for the identification of proteins
      clinically relevant as new biomarkers or as drug targets. For this purpose a
      differential label-free nano-LC ESI/QTOF mass spectrometry (MS) approach combined
      with targeted MS/MS analysis has been developed and applied to isolated IECs. We
      report here a study of the protein variations in IECs from healthy subjects (H)
      and Crohn's disease patients (CD). The method was previously validated using HT29
      Cl.16E cell line, normal or treated with interferon-gamma as a model of
      inflammation. Subcellular fractions proteins were extracted from HT29 and IECs
      and for each fraction monodimensional gel-electrophoresis was performed and the
      proteins subjected to tryptic digestion. The resulting peptides were analysed by
      LC ESI/QTOF MS and the obtained chromatographic runs were aligned with msInspect
      software. The peptides differently expressed were statistically evaluated using
      the Proteios Software Environment (ProSE) and identified by LC ESI/QTOF MS/MS
      analysis and database search. The preliminary results obtained allowed the
      identification of many proteins involved in the inflammation processes.

PMID- 19168160
TI  - Risk of fracture in women treated with monthly oral ibandronate or weekly
      bisphosphonates: the eValuation of IBandronate Efficacy (VIBE) database fracture
      study.
AB  - The eValuation of IBandronate Efficacy (VIBE) head-to-head database fracture
      study compared fracture rates between patients treated with monthly ibandronate
      and weekly oral bisphosphonates (BPs). This large study included women >/=45
      years old, newly prescribed monthly oral ibandronate or weekly oral alendronate
      or risedronate, and without malignancy or Paget's disease of bone. The primary
      analysis included patients who were adherent to treatment during the first 90
      days after the index date. The risks of hip, nonvertebral, vertebral and any
      clinical fracture were compared using Cox proportional hazards models and
      adjusted for potential confounding factors. A secondary, "intent-to-treat"
      analysis included all patients who received at least one BP prescription.
      Sensitivity analyses based on the primary analysis compared patients receiving
      ibandronate with patients receiving weekly alendronate or risedronate separately,
      and explored the effect of excluding patients with potential confounding factors
      from the analysis. Further sensitivity analyses varied the requirement for
      adherence during the first 90 days after the index date. The primary analysis
      population included 7345 monthly ibandronate and 56,837 weekly BP patients.
      Fracture rates after the 12-month observational period were <2% and fracture risk
      was not significantly different between patients receiving monthly ibandronate or
      weekly BPs for hip, nonvertebral or any clinical fracture (adjusted relative
      risk: hip=1.06, p=0.84; nonvertebral=0.88, p=0.255; any clinical fracture=0.82,
      p=0.052). Ibandronate patients had a significantly lower risk of vertebral
      fracture than weekly BP patients (adjusted relative risk 0.36, 95% confidence
      interval 0.18-0.75, p=0.006). In the secondary, "intent-to-treat" analysis,
      relative risks of fracture were not significantly different between treatment
      groups for any fracture type. The results of the sensitivity analyses were
      generally consistent with the primary analysis. This retrospective cohort study
      found that patients treated with oral monthly ibandronate or weekly BPs
      (alendronate and risedronate) had similar, low risks of hip fracture,
      nonvertebral fracture and any clinical fracture. Ibandronate patients had a
      significantly lower relative risk of vertebral fracture than weekly BP patients;
      the clinical implications of these findings require further exploration and
      validation.

PMID- 19168161
TI  - Effect of long-term intervention of soy isoflavones on bone mineral density in
      women: a meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: A number of RCTs have examined the role of soy isoflavones on bone
      mineral density (BMD) and yielded inconsistent results. This meta-analyses aims
      to assess the overall effect of soy isoflavones on BMD. METHODS: We searched for
      all articles published in English from January 1990 to March, 2008. We included
      RCTs of soy isoflavone supplementation in women of at least one year duration.
      The main outcomes were BMD changes from baseline at the lumbar spine, total hip
      and femoral neck. RESULTS: We identified 10 eligible RCTs containing 896 women. A
      mean dose of 87 mg soy isoflavones for at least one year did not significantly
      affect BMD changes. The mean (95%CI) differences in BMD changes (in
      mg/cm(2)/year) were 4.1 (-1.6, 9.8) (0.4%) at the lumbar spine, -1.5 (-7.2, 4.3)
      (-0.3%) at the femoral neck under random-effects model, and 2.5 (-0.5, 5.4)
      (0.2%) at the total hip by fix-effects model, respectively. Similar results were
      obtained in subgroup analyses by isoflavone sources (soy protein vs. isoflavone
      extract), ethnic differences (Asian vs. Western). Larger dose (>or=80 mg/d), but
      not lower dose (<80 mg/d), of isoflavone intervention tended to have a weak
      beneficial effect on spine BMD (p=0.08 vs. p=0.94). CONCLUSIONS: Soy isoflavone
      supplementation is unlikely to have significant favorable on BMD at the lumbar
      spine and hip in women.

PMID- 19168162
TI  - Bone mineral density of the spine and femur in a group of healthy Moroccan men.
AB  - BACKGROUND: Bone mineral density (BMD) measurements using dual-energy X-rays
      absorptiometry (DXA) are widely used to diagnose osteoporosis and to assess its
      severity. Previous studies show the necessity to establish reference data for
      bone mass measurements for each particular population. Such data are lacking for
      the male Moroccan population. AIM: To establish reference values for the healthy
      Moroccan male population and to compare them with those for Caucasian and Arab
      males, and to study the impact of different curves implemented in the DXA system
      on the diagnosis of osteoporosis. METHODS: A cross-sectional study of 592
      Moroccan men, recruited from the area of Rabat, the capital of Morocco, aged
      between 20 and 79 years was carried to establish reference values of bone mineral
      density. Measurements were taken at the lumbar spine and proximal femurs using
      DXA (Lunar Prodigy Vision, GE). The data were compared with published normative
      taken by US, European, Iranian, Lebanese, and Saudi men over six decades of age.
      Impact on osteoporosis diagnosis according to the WHO criteria using the
      personalized curve and US (NHANES), European and Middle-East reference curves (as
      implemented in the Lunar densitometers) was studied. RESULTS: Our results showed
      that the Moroccan men showed the expected decline in BMD at both sites with age
      after peaking at 20-29 years age group. Every anatomical region has a different
      rate of bone loss: lumbar spine (0.3% per year) femoral neck (0.6%), trochanter
      (0.3%), and total hip (0.4%). The lumbar spine and femoral subregions BMD
      exhibited increases from 0.3 to 0.5% per kilogram of body weight. In the spine,
      the US/European Lunar reference values classified a larger proportion of men as
      osteoporotic (18.1% vs. 7.4%) while using the Arabic Lunar reference values, only
      7.8% were classified as osteoporotic. However, using Arabic curve for the femurs
      resulted in underdiagnosis of osteoporosis (1.8% vs. 6.0%), whereas the
      US/European Lunar reference values classified men as osteoporotic in 3.9% and
      5.3% respectively. DISCUSSION: In comparison with the other Countries, the spine
      BMD of Moroccan men were slightly lower than Iranian's, Europeans and Brazilians
      but higher than the Saudi and Lebanese males. We found BMD values taken at the
      lumbar spine to be around 4% lower than European values between ages 50 and 59
      years, and 10% lower for older subjects. These values were 4-6% higher than
      Saudis/Lebanese values between ages 20-39. For older subjects, Moroccan values
      were more than 10% higher than Saudis and almost similar to Lebanese. Femoral
      neck BMD values were 8% higher in young adults (age 20-39 years) to
      US/Saudis/Lebanese values, but about 10% lower in ages over 60 to US values
      whereas it was similar to Saudis and Lebanese values. CONCLUSION: Our study
      emphasises the importance of using population-specific reference values for BMD
      measurements to avoid over or underdiagnosis of osteoporosis.

PMID- 19168163
TI  - Associations of genetic lactase non-persistence and sex with bone loss in young
      adulthood.
AB  - Some studies have reported that after attainment of peak bone mass (PBM), slow
      bone loss may occur in both men and women; however, findings are inconsistent.
      Genetic factors play a significant role in bone loss, but the available evidence
      is conflicting. Genetic lactase non-persistence (lactase C/C(-13910) genotype) is
      suggested to increase risk for inadequate calcium intake predisposing to poorer
      bone health. We investigated whether this genotype is associated with PBM and
      bone loss in young Finnish adults. Subjects belong to the Cardiovascular Risk in
      Young Finns Study that is an ongoing multi-centre follow-up of atherosclerosis
      risk factors. From the original cohort, randomly selected subjects aged 20-29
      participated in baseline bone mineral density (BMD) measurements (n=358), and in
      follow-up measurements 12 years later (n=157). Bone mineral content (BMC) and BMD
      at lumbar spine (LS) and femoral neck (FN) were measured at baseline and follow
      up with dual energy X-ray absorptiometry (DXA). Lactase C/T(-13910) polymorphism
      was determined by PCR and allele-specific fluorogenic probes. Information on
      lifestyle was elicited with questionnaires. During the follow-up, bone loss at
      both bone sites was greater in males (LS BMD: -1.1%, FN BMD: -5.2%) than in
      females (LS BMD: +2.1%, FN BMD: -0.7%) (both bone sites p=0.001). Younger age
      predicted greater loss of FN BMC and BMD in females (p=0.013 and p=0.001,
      respectively). Increased calcium intake predicted FN BMD gain in both sexes (in
      females B=0.007 g/cm(2)/mg, p=0.002; in males B=0.006, p=0.045), and increased
      physical activity LS BMD gain in females (B=0.091 g/cm(2)/physical activity
      point, p=0.023). PBM did not differ between the lactase genotypes, but males with
      the CC(-13910) genotype seemed to be prone to greater bone loss during the follow
      up (LS BMD: C/C vs. T/T p=0.081). In conclusion, bone loss in young adulthood was
      more common in males than in females and seemed to occur mainly at the femoral
      neck. Young males with the lactase CC(-13910) genotype may be more susceptible to
      bone loss; however, calcium intake predicts changes in bone mass more than the
      lactase genotype.

PMID- 19168164
TI  - Bone matrix quality and plasma homocysteine levels.
AB  - It has recently been reported in the clinical literature that blood homocysteine
      levels correlate well with fracture risk, although a couple of reports exist to
      the opposite. Bone strength depends on both bone quantity and quality. The
      purpose of the present study was to investigate possible correlations between
      plasma homocysteine levels and bone material properties (Bone Mineral Density
      Distribution; BMDD, and collagen cross-link ratio). In the present study, femoral
      heads from subjects (N=19, females, age range 70-95 years old) with known
      homocysteine plasma levels were investigated. The bone material was collected
      during hemiarthroplasty surgery. We have determined collagen cross-link ratio and
      bone mineralization density distribution (BMDD) in bone tissue from patients with
      acute femoral neck fractures, by Fourier Transform Infrared Imaging (FTIRI) and
      quantitative Backscattered Electron Imaging (qBEI), respectively. The collagen
      cross-link ratio that was spectroscopically determined was pyridinoline/divalent
      cross-links (pyr/divalent). The BMDD variables quantified were: CaMean: the
      weighted mean calcium concentration; CaPeak: the most frequent Ca concentration;
      CaWidth: the width of the distribution, a measure of the mineralization
      homogeneity; CaLow: the percentage of bone area that is mineralized below the 5th
      percentile in the reference range; CaHigh: the percentage of bone area that is
      mineralized above the 95th percentile in the reference range. There was a
      significant correlation between plasma homocysteine levels and collagen cross
      link ratio in areas of primary mineralized bone (p<0.0001), unlike the case of
      trabecular bone surfaces undergoing resorption (p>0.05). On the other hand there
      was no correlation in any of the BMDD parameters and plasma homocysteine levels
      (p>0.05). The results are consistent with the known effect of homocysteine on
      collagen post-translational modifications. These changes were independent of bone
      mineral characteristics. The results of the present study offer a mechanism by
      which homocysteine affects bone quality, but caution should be exercised since
      all patients examined had sustained fracture.

PMID- 19168165
TI  - Bone loss in the lower leg during 35 days of bed rest is predominantly from the
      cortical compartment.
AB  - Immobilization-induced bone loss is usually greater in the epiphyses than in the
      diaphyses. The larger fraction of trabecular bone in the epiphyses than in the
      diaphyses offers an intuitive explanation to account for this phenomenon.
      However, recent evidence contradicts this notion and suggests that immobilization
      induced bone loss from the distal tibia epiphysis is mainly from the cortical
      compartment. The aim of this study was to establish whether this pattern of bone
      loss was a general rule during immobilization. We monitored various skeletal
      sites with different tissue composition during 5 weeks of immobilization. Ten
      healthy male volunteers with mean age of 24.3 years (SD 2.6 years) underwent
      strict horizontal bed rest. Bone scans were obtained during baseline data
      collection, at the end of bed rest and after 14 days of recovery by peripheral
      Quantitative Computed Tomography (pQCT). Sectional images were obtained from the
      distal tibia epiphysis (at 4% of the tibia's length), from the diaphysis (at
      38%), from the proximal metaphysis (at 93%) and from the proximal epiphysis (at
      98%), as well as from the distal femur epiphysis (at 4% of the femur's length)
      and from the patella. Relative bone losses were largest at the patella, where
      they amounted to -3.2% (SD 1.8%, p<0.001) of the baseline values, and smallest at
      the tibia diaphysis, where they amounted to -0.7% (SD 1.0%, p=0.019). The
      relative losses were generally larger from cortical than from trabecular
      compartments (p=0.004), and whilst all skeletal sites depicted such cortical
      losses, substantial trabecular losses were found only from the proximal tibia
      epiphysis. Results confirm that the differential losses from the various skeletal
      sites cannot be explained on the basis of trabecular vs. cortical tissue
      composition differences, but that endocortical circumference can account for the
      different amounts of bone loss in the tibia. The present study therefore supports
      the suggestion of the subendocortical layer as a transitional zone, which can
      readily be transformed into trabecular bone in response to immobilization. The
      latter will lead to cortical thinning, a factor that has been associated with the
      risk of fracture and with osteoarthritis.

PMID- 19168166
TI  - Cysteine, homocysteine and bone mineral density: a role for body composition?
AB  - BACKGROUND: Plasma total cysteine (tCys) and homocysteine (tHcy) are associated
      with body composition, which in turn affects bone mineral density (BMD).
      OBJECTIVES: To investigate whether associations of tCys and tHcy with BMD are
      mediated through body composition (fat mass and/or lean mass). DESIGN: Using data
      from 5238 Hordaland Homocysteine Study participants, we fit multiple linear
      regression models and concentration-response curves to explore the relationships
      between tCys, tHcy, and BMD, with and without adjustment for body mass index
      (BMI), lean mass and/or fat mass. RESULTS: All associations were stronger in
      women. tCys was positively associated with BMD (women, partial r=0.11; men,
      partial r=0.07, p<or=0.001 for both), but this association was markedly
      attenuated after adjustment for fat mass. tHcy showed an inverse association with
      BMD in women (partial r=-0.09, p<0.001), which remained significant after
      adjustment for lean mass and fat mass. In men and women, changes in tCys or tHcy
      during 6 years were not associated with BMD at follow-up. Weight gain during 6
      years predicted higher BMD at follow-up (p<or=0.009) independent of nutrient
      intakes, physical activity and baseline BMI. Baseline tHcy inversely predicted
      BMD measured 6 years later (partial r=-0.11, p<0.001 in women; partial r=-0.07,
      p=0.002 in men) independent of baseline BMI, while a positive association of
      baseline tCys with BMD at follow-up (partial r=0.10 in women, 0.09 in men,
      p<or=0.001) disappeared after adjustment for baseline BMI. CONCLUSION: tHcy is
      inversely associated with BMD independent of body composition, while the positive
      association of tCys with BMD appears to be mainly mediated through fat mass.

PMID- 19168167
TI  - Long term oncostatin M treatment induces an osteocyte-like differentiation on
      osteosarcoma and calvaria cells.
AB  - Previous in vitro studies on primary osteoblastic and osteosarcoma cells (normal
      and transformed osteoblasts) have shown that oncostatin M (OSM), a member of the
      interleukin-6 family, possesses cytostatic and pro-apoptotic effects in
      association with complex and poorly understood activities on osteoblast
      differentiation. In this study, we use rat osteosarcoma cells transduced with
      lentiviral particles encoding OSM (lvOSM) to stably produce this cytokine. We
      show that after several weeks of culture, transduced OSRGA and ROS 17/2.8 cells
      are growth inhibited and sensitized to apoptosis induced by the kinase inhibitor
      Staurosporine (Sts). Moreover, this long term OSM treatment induces (i) a
      decrease in osteoblastic markers, (ii) morphological changes leading to an
      elongated and/or stellate shape and (iii) an increase in osteocytic markers
      (sclerostin and/or E11), suggesting an osteocyte-like differentiation. We also
      show that non transformed rat calvaria cells transduced with lvOSM differentiate
      into stellate shaped cells expressing sclerostin, E11, Phex and functional
      hemichannels. Together, these results indicate that osteosarcoma cells stably
      producing OSM do not develop resistance to this cytokine and thus could be a
      valuable new tool to study the anti-cancer effect of OSM in vivo. Moreover, OSM
      over-expressing osteoblastic cells differentiate into osteocyte-like cells, the
      major cellular contingent in bone, providing new culture conditions for this cell
      type which is difficult to obtain in vitro.

PMID- 19168168
TI  - Active management of risk in nulliparous pregnancy at term: association between a
      higher preventive labor induction rate and improved birth outcomes.
AB  - OBJECTIVE: The objective of the study was to determine whether exposure of
      nulliparous women to a high rate of preventive labor induction was associated
      with improvement in birth health. STUDY DESIGN: A risk-scoring system was used to
      guide the frequent use of preventive labor induction in 100 nulliparous women.
      The birth outcomes of this group were compared with those of 352 nulliparous
      women who received usual care. Cesarean delivery was the primary study outcome.
      The Adverse Outcome Index and the rate of uncomplicated vaginal delivery were
      used to measure overall birth health. RESULTS: The exposed group experienced a
      higher labor induction rate (48% vs 23.6%; P < .001), a lower cesarean rate (9%
      vs 25.8%; adjusted odds ratio, 0.36; P = .02), and better composite birth
      outcomes. CONCLUSION: Exposure of nulliparous women to a high preventive
      induction rate was significantly associated with improvement in birth health.
      Prospective randomized trials are needed to further explore the utility of risk
      guided preventive labor induction.

PMID- 19168169
TI  - Circulating angiogenic factors in gestational proteinuria without hypertension.
AB  - OBJECTIVE: Our goal was to determine whether obstetric outcomes and serum
      angiogenic factors are altered in women with gestational proteinuria without
      hypertension. STUDY DESIGN: We performed a nested case-control study of 108 women
      with gestational proteinuria and compared them with 1564 randomly selected women
      with normotension without proteinuria during pregnancy (control subjects) and
      with 319 women who experienced preeclampsia. RESULTS: Women with gestational
      proteinuria had greater body-mass index and higher blood pressure at study
      enrollment. Adverse obstetric outcomes were infrequent. Levels of free placental
      growth factor were lower than control levels beginning early in gestation.
      Compared with gestational-age matched control subjects, free placental growth
      factor was reduced beginning 6-8 weeks before proteinuria. Although soluble fms
      like tyrosine kinase 1 and soluble endoglin concentrations were elevated 1-2
      weeks before proteinuria, these elevations were modest and transient. After the
      onset of proteinuria, angiogenic factor levels generally did not differ
      significantly from control levels. CONCLUSION: Gestational proteinuria in healthy
      nulliparous women appears to be a mild variant of preeclampsia.

PMID- 19168170
TI  - Neonatal hypoglycemia in term, nondiabetic pregnancies.
AB  - OBJECTIVE: To define the incidence of hypoglycemia and identify risk factors in
      neonates from term, singleton, nondiabetic pregnancies. STUDY DESIGN: We
      conducted a matched case-control study of term, singleton infants weighing more
      than 2500 g in nondiabetic pregnancies. Cases with hypoglycemia (glucose < 50
      mg/dL) were identified by International Classification of Diseases, ninth
      revision, codes. Two controls per case were matched on race, maternal age, and
      birthweight. Conditional logistic regression analyses were performed. RESULTS:
      There were 116 cases and 232 controls studied. The incidence density of neonatal
      hypoglycemia was 24.7 per 1000 infant-days at risk. Hypoglycemia was less
      commonly associated with later gestational age (odds ratio [OR], 0.66; 95%
      confidence interval [CI], 0.53-0.85 per week of gestation). Maternal fever during
      labor was more common with hypoglycemia (OR, 4.08; 95% CI, 1.39-11.79). Public
      insurance was more than twice as common with hypoglycemia compared with those
      privately insured (OR, 2.31; 95% CI, 1.17-4.58). CONCLUSION: Neonatal
      hypoglycemia was associated with earlier gestational age, intrapartum fever, and
      public insurance.

PMID- 19168171
TI  - The relationship between superior attachment points for anterior wall mesh
      operations and the upper vagina using a 3-dimensional magnetic resonance model in
      women with normal support.
AB  - OBJECTIVE: We examined structural relationships between anterior mesh kit
      suspension points and the upper vagina in women with normal support. STUDY
      DESIGN: Eleven women with normal support underwent supine, multiplanar magnetic
      resonance pelvic imaging at rest and maximal Valsalva. Using 3-dimensional models
      generated from these images, anterior wall mesh kit anchoring points were
      identified along the arcus tendineus fascia pelvis. We then measured the
      percentage of anterior vagina above and posterior to superior suspension points.
      RESULTS: The anterior vagina extended above superior attachment points in 100% of
      women at rest and in 73% during Valsalva. It extended posterior to them in 82%
      and 100% (rest and Valsalva, respectively). The mean percentage of anterior
      vaginal length above superior anchoring sites was 40 +/- 14% at rest and 29 +/-
      12% during Valsalva. CONCLUSION: The upper vagina lies above and posterior to
      superior suspension points in the majority of women with normal support.

PMID- 19168172
TI  - Change in quantitative human chorionic gonadotropin after manual vacuum
      aspiration in women with pregnancy of unknown location.
AB  - OBJECTIVE: To determine whether the change in human chorionic gonadotropin after
      manual vacuum aspiration is predictive of an early abnormal intrauterine
      pregnancy in women with pregnancy of unknown location. STUDY DESIGN: This is a
      prospective cohort study of 23 clinically stable patients with an early abnormal
      pregnancy who had abnormally rising human chorionic gonadotropins and absence of
      sonographic evidence of an intrauterine pregnancy or ectopic pregnancy. The
      change in human chorionic gonadotropin within 24 hours after manual vacuum
      aspiration was compared with the pathologic diagnosis and the ultimate clinical
      diagnosis. RESULTS: Ten patients had > or = 50% decrease (mean, 74%; range, 58
      80%) in human chorionic gonadotropin after manual vacuum aspiration with
      confirmed chorionic villi on pathology results. Two patients had a > 50% drop in
      human chorionic gonadotropin but absence of chorionic villi, clinically
      consistent with complete spontaneous abortion. The remaining 10 patients who had
      either rising or < 50% decrease in human chorionic gonadotropin post manual
      vacuum aspiration all had no chorionic villi on pathology results. The
      sensitivity, specificity, positive predictive value, and negative predictive
      value of a > or = 50% decrease in human chorionic gonadotropin after manual
      vacuum aspiration in predicting an abnormal intrauterine pregnancy were 92% (95%
      confidence interval [CI], 0.62-0.99), 100% (95% CI, 0.62-1.0), 100% (95% CI, 0.70
      1.0), and 90% (95% CI, 0.54-0.99), respectively. CONCLUSION: A > or = 50%
      decrease in human chorionic gonadotropin within 24 hours after manual vacuum
      aspiration is predictive of an abnormal intrauterine pregnancy, thereby excluding
      an ectopic pregnancy and expediting the management of women with pregnancy of
      unknown location.

PMID- 19168173
TI  - Regulating emotion during imaginal exposure to social anxiety: impact of the
      specificity of information processing.
AB  - The present study investigates the emotional impact of a specific vs. generic
      mode of information processing during imaginal exposure. Forty-nine socially
      anxious students mentally relived a personally experienced stressful social
      situation. Half of the participants were instructed to activate generic elements
      of the target event (i.e., elements repetitively experienced in similar social
      situations); the other half had to recall the specific features of the target
      event. Results showed that participants who focused on specific elements reported
      less distress than those who focused on generic features. Clinical implications
      are discussed.

PMID- 19168174
TI  - Self-perceived competence and prospective changes in symptoms of depression and
      social anxiety.
AB  - The primary aim of the current study was to replicate and extend previous
      findings by examining the relation of self-perceived competence with symptoms of
      depression and social anxiety in older adolescents. Focusing first on cross
      sectional relations, we found that older adolescents' depressive symptoms were
      similarly related to levels of perceived scholastic competence and social
      acceptance, whereas social anxiety was significantly more strongly related to
      perceived social acceptance. Next, examining symptom changes over a six-month
      follow-up, we found that perceived social acceptance and scholastic competence
      both independently predicted prospective changes in adolescents' depressive
      symptoms, whereas perceived social acceptance, but not scholastic competence,
      predicted prospective changes in social anxiety. Although we also examined
      vulnerability-stress models of symptom change with negative academic and social
      events, none of these analyses was significant.

PMID- 19168175
TI  - A comment on assessment of sex using the skull.

PMID- 19168176
TI  - Stabilisation of vertical unstable distal clavicular fractures (Neer 2b) using
      locking T-plates and suture anchors.
AB  - Distal clavicular fractures are associated with an increased risk of delayed
      union and non-union, and therefore operative treatment is favoured. Fragment
      dislocation and instability result from detachment of the coracoclavicular
      ligaments. Various methods for operative treatment can be found in the
      literature, but no gold standard has been established. In this retrospective
      study, we present a new surgical technique using a locking T-plate for osseous
      stabilisation in combination with vertical stabilisation by suture anchors.
      Between October 2006 and December 2007, eight people underwent surgery for
      unstable distal clavicular fracture (Neer type 2b). Subsequently one patient
      could only be contacted by phone and was excluded from further analysis. Mean
      follow-up for the remaining seven individuals was 8.3 months. The Constant and
      DASH scores were evaluated and stress radiographs were performed to check for
      vertical instability. In all cases bony union was achieved within 6 weeks
      postoperatively. No intraoperative or early postoperative complications were
      observed. All but one patient regained excellent shoulder function, the mean
      Constant and DASH scores were 93.3 and 15.3, respectively. Coracoclavicular
      distance was successfully restored with a mean 1mm (range 0-2mm) side-to-side
      difference. Early clinical and radiographic results of this new method are
      promising, with good to excellent outcome in all cases.

PMID- 19168177
TI  - Surface extenders and an optimal pore size promote high dynamic binding
      capacities of antibodies on cation exchange resins.
AB  - Increased recombinant protein expression yields and a large installed base of
      manufacturing facilities designed for smaller bulk sizes has led to the need for
      high capacity chromatographic resins. This work explores the impact of three pore
      sizes (with dextran distribution coefficients of 0.4, 0.53, and 0.64), dextran
      surface extender concentration (11-20mg/mL), and ligand density (77-138 micromol
      H+/mL resin) of cation exchange resins on the dynamic binding capacity of a
      therapeutic antibody. An intermediate optimal pore size was identified from three
      pore sizes examined. Increasing ligand density was shown to increase the critical
      ionic strength, while increasing dextran content increased dynamic binding
      capacity mainly at the optimal pore size and lower conductivities. Dynamic
      binding capacity as high as 200mg/mL was obtained at the optimum pore size and
      dextran content.

PMID- 19168178
TI  - Reversed-phase liquid chromatography using mandelic acid as an eluent for the
      determination of uranium in presence of large amounts of thorium.
AB  - Studies were carried out for the separation of uranium (U) and thorium (Th) on
      reversed-phase (RP) C18 columns using mandelic acid as an eluent. Retention of
      thorium-mandelate on the unmodified stationary phase was found to be greater than
      that of uranyl-mandelate under the pH conditions employed. Th retention capacity
      of the stationary phase was determined as a function of pH and MeOH content of
      the mobile phase. The optimised parameters allowing U elution prior to Th were
      utilized for the determination of small amounts of U in the presence of large
      amounts of Th. The method has been used for the determination of U in synthetic
      samples with Th/U amount ratios up to 100,000 (10 microg/g of U) without any pre
      separation, employing a particulate C18 column. Effect of concentration of ion
      interaction reagents (IIRs) on the retention was studied to understand the
      mechanism of adsorption of their mandelate complexes onto the stationary phase.
      The experiments conducted unequivocally prove that thorium-mandelate complex is
      neutral whereas uranyl-mandelate complex is anionic in nature.

PMID- 19168179
TI  - Fast high-throughput method for the determination of acidity constants by
      capillary electrophoresis: I. Monoprotic weak acids and bases.
AB  - A new and fast method to determine acidity constants of monoprotic weak acids and
      bases by capillary zone electrophoresis based on the use of an internal standard
      (compound of similar nature and acidity constant as the analyte) has been
      developed. This method requires only two electrophoretic runs for the
      determination of an acidity constant: a first one at a pH where both analyte and
      internal standard are totally ionized, and a second one at another pH where both
      are partially ionized. Furthermore, the method is not pH dependent, so an
      accurate measure of the pH of the buffer solutions is not needed. The acidity
      constants of several phenols and amines have been measured using internal
      standards of known pK(a), obtaining a mean deviation of 0.05 pH units compared to
      the literature values.

PMID- 19168180
TI  - Solid-phase extraction combined with dispersive liquid-liquid microextraction for
      the determination for polybrominated diphenyl ethers in different environmental
      matrices.
AB  - An analytical method, solid-phase extraction combined with dispersive liquid
      liquid microextration (SPE-DLLME), was established to determine polybrominated
      diphenyl ethers (PBDEs) in water and plant samples. After concentration and
      purification of the samples in LC-C18 column, 1.0-mL elution sample containing
      22.0 microL 1,1,2,2-tetrachloroethane was injected rapidly into the 5.0-mL pure
      water. After extraction and centrifuging, the sedimented phase was injected
      rapidly into gas chromatography with electron-capture detection (GC-ECD). For
      water samples, enrichment factors (EFs) are in the range of 6838-9405 under the
      optimum conditions. The calibration curves are linear in the range of 0.1-100 ng
      L(-1) (BDEs 28, 47) and 0.5-500 ng L(-1) (BDEs 100, 99, 85, 154, 153). The
      relative standard deviations (RSDs) and the limits of detection (LODs) are in the
      range of 4.2-7.9% (n=5) and 0.03-0.15 ng L(-1), respectively. For plant samples,
      RSDs and LODs are in the range of 5.9-11.3% and 0.04-0.16 microg kg(-1),
      respectively. The relative recoveries of well, river, sea, leachate, and clover
      samples, spiked with different levels of PBDEs, are 66.8-94.1%, 72.2-100.5%, 74.5
      110.4%, 62.1-105.1%, 66.1-91.7%, 62.4-88.9%, and 64.5-83.2%, respectively. The
      results show that SPE-DLLME is a suitable method for the determination of PBDEs
      in water and plant samples.

PMID- 19168181
TI  - Standard systems for measurement of pK values and ionic mobilities: 2. Univalent
      weak bases.
AB  - This paper contributes to the methodology of measuring pK values and ionic
      mobilities by capillary zone electrophoresis by introducing the principle of
      constant ionic strength and minimum interaction of analytes with counterionic
      components and presenting a standard system of cationic buffers for measurements
      of weak bases. The system is designed so that all buffers comprise the same
      concentration of Cl(-) present as the only counter anion. This minimizes problems
      caused by interactions between the counterion and the analytes which may
      otherwise bring biased values of obtained effective mobilities. Further, the
      buffer system provides constant and accurately known ionic strength for an entire
      set of measurements. When additionally all measurements are performed with
      constant Joule heating, one correction for ionic strength and temperature is then
      needed for the obtained set of experimental data. This considerably facilitates
      their evaluation and regression analysis as the corrections for ionic strength
      and Joule heating need not be implemented in the computation software and may be
      applied only once to the final regression results. An experimental example of the
      proposed methodology is presented and the reliability and the advantages of the
      proposed system are shown, where the known problematic groups of amines and
      pyridine were measured with high accuracy and without any notice of anomalous
      behavior.

PMID- 19168182
TI  - Separation of protein mixtures using pH-gradient cation-exchange chromatography.
AB  - Historically, separation of a protein mixture after adsorption to a cation
      exchange column is effected by alteration in ionic strength. An alternative
      separation method using pH induced gradient in the range of 4-7.5 was studied. A
      cation-exchange column with large particle beads containing excessive carboxyls
      was employed. A pH gradient across the column was generated by a step change at
      the column entrance using a non-retained buffer system. Consistency and accuracy
      of pH values in timed intervals were demonstrated in three different batches. In
      development of the application, we found a correlation coefficient of >0.9
      between the elution pH values of six acidic proteins and their isoelectric
      points. One case study showed the resolution between a monoclonal antibody and
      non-retained protein species from a protein A column. Another case study showed
      the feasibility of separating polyethylene glycol conjugated protein from native
      protein.

PMID- 19168183
TI  - Characterization of weld (Reseda luteola L.) and spurge flax (Daphne gnidium L.)
      by high-performance liquid chromatography-diode array detection-mass spectrometry
      in Arraiolos historical textiles.
AB  - The natural dyes, and dye sources, in two seventeenth century Arraiolos carpets
      from the National Museum of Machado de Castro were analysed by high-performance
      liquid chromatography with UV-vis diode array detection (HPLC-DAD) and HPLC-mass
      spectrometry (LC-MS). Weld (Reseda luteola L.), indigo and spurge flax (Daphne
      gnidium L.) were found to be the dye sources, in agreement with original dyeing
      recipes collected during the nineteenth century. In order to fully characterize
      the plant sources, LC-MS conditions were optimized with plant extracts and the
      chromatographic separation and mass detection were enhanced. Extraction of the
      dyes, in the Arraiolos carpet samples, was performed using mild conditions that
      avoid glycoside decomposition. For the blues a dimethylformamide solution proved
      to be efficient for indigotin recovery. For all the other colours, an improved
      mild extraction method (with oxalic acid, methanol, acetone and water) was used,
      enabling to obtain the full dye source fingerprint, namely the flavonoid
      glycosides in the yellow dyes.

PMID- 19168184
TI  - Angiotensin I retention behavior on Butyl-Sepharose under linear loading
      chromatographic conditions.
AB  - Adsorption behavior of angiotensin I on a commercial Butyl-Sepharose support has
      been studied in function of temperature and ammonium sulphate concentration.
      Under isocratic elution conditions and at the higher salt concentrations, a
      characteristic of the chromatographic performance of angiotensin I was the
      broadness of the corresponding peak and in most of the cases the appearance of
      two peaks. These results have been interpreted in terms of on-column cis-trans
      isomerization of angiotensin I (a proline containing polypeptide) followed by its
      "re-conformation" after the interaction with the support. It has been proposed
      that the peak splitting phenomenon, a combined effect between temperature, salt
      concentration in the mobile phase and the ligand, is caused by slow kinetics of
      isomerization that is on the same time scale as the chromatographic separation.
      Salt concentration and temperature promote the conversion of the trans form of
      angiotensin I into its cis form, which has a bigger hydrophobic surface area, in
      the presence of Butyl-Sepharose. The retention of the cis form of angiotensin I
      increases with the increase in salt concentration in the mobile phase and seems
      to be little affected by temperature.

PMID- 19168185
TI  - Determination of proanthocyanidin A2 content in phenolic polymer isolates by
      reversed-phase high-performance liquid chromatography.
AB  - This article summarizes the development of an analytical method for the
      determination of proanthocyanidin (PAC) A2 in phenolic polymer isolates following
      acid-catalyzed degradation in the presence of excess phloroglucinol. Isolates
      from concentrated cranberry juice (CCJ) were extensively characterized and molar
      extinction coefficients were determined for the terminal A2 and phloroglucinol
      adduct of the extension A2 unit. Peanuts were also found to contain both
      extension and terminal A-type PACs and therefore a total peanut system (TPS) was
      chosen to test the effectiveness of the HPLC method that was developed with the
      CCJ system. Kinetic studies were conducted and reaction conditions were optimized
      for the A2 units in both CCJ and TPS. The optimized method provides quantitative
      and reproducible information on the A2 content of proanthocyanidin isolates.

PMID- 19168186
TI  - Influence of atmospheric fluorine plasma treatment on thermal and dielectric
      properties of polyimide film.
AB  - Plasma treatment of polyimide surfaces not only causes structural modification
      during the plasma exposure, but also leaves active sites on the surfaces that are
      subject to post-reaction. In this work, the effects of atmospheric fluorine
      plasma treatment on the surface properties and dielectric properties of polyimide
      thin film were investigated by using X-ray photoelectron spectroscopy (XPS),
      Fourier transform-IR (FT-IR) spectroscopy, and contact angle measurement. The
      results indicated that plasma treatment successfully introduced fluorine
      functional groups on the polyimide surfaces. The polyimides also exhibited good
      thermal stability and a lower dielectric constant. It appears that the
      replacement of fluorine led to the decrease of the local electronic
      polarizability of polyimide. Consequently, it was found that the atmospheric
      fluorine plasma-treated polyimides possessed lower dielectric characteristics
      than the untreated polyimides.

PMID- 19168187
TI  - Surface-initiated ATRP of PMMA, PS and diblock PS-b-PMMA copolymers from
      stainless steel modified by 11-(2-bromoisobutyrate)-undecyl-1-phosphonic acid.
AB  - A new ATRP initiator, 11-(2-bromoisobutyrate)-undecyl-1-phosphonic acid, has been
      synthesized and grafted as a film on a mechanically polished stainless steel
      (ASI304) substrate. Molecular integrity of the grafted initiator in the film,
      alkyl chain ordering, wettability were determined by X-ray photoelectron
      spectroscopy, infrared, and water contact angles. Polystyrene, poly(methyl
      methacrylate) and diblock copolymer (polystyrene-b-poly(methyl methacrylate))
      brushes have been grafted from the flat stainless steel surfaces through surface
      initiated atom transfer radical polymerization (ATRP) and characterized to check
      the effectiveness of the new initiator for future uses in surface-initiated ATRP.

PMID- 19168188
TI  - Preparation and characterization of thermo-responsive PDMS surfaces grafted with
      poly(N-isopropylacrylamide) by benzophenone-initiated photopolymerization.
AB  - In the preparation of a thermo-responsive, poly(N-isopropylacrylamide) (PNIPAAm)
      grafted polydimethylsiloxane (PDMS) surface by means of benzophenone-initiated
      photopolymerization, we observed that thick (>1 mm) PDMS substrates were much
      more difficult to be grafted with PNIPAAm than thin ones. Investigations revealed
      that the shortage of diffused benzophenone molecules in the surface region of the
      thick substrate might be the reason. By prolonging the time spent for treating
      the substrate with a benzophenone solution, PNIPAAm could be successfully grafted
      onto thick PDMS substrates. The PNIPAAm-grafted PDMS surface was highly thermo
      responsive. The contact angle on a grafted surface increased from 38 to 91
      degrees in response to the temperature increase from 20 to 38 degrees C. An
      electroosmotic flow (EOF) mobility of 5x10(-4) cm(2)/Vs was supported by a
      PNIPAAm-grafted PDMS channel at 50 degrees C, whereas negligible EOF was observed
      at 20 degrees C. Doxorubicin (DX), an anticancer drug, was adsorbed by the
      grafted surface at 40 degrees C, and the majority of the adsorbed DX was quickly
      released from the surface to a stripping solution at 5 degrees C. Osteoblast
      cells adhered onto the PNIPAAm-grafted PDMS surface and proliferated therein at
      37 degrees C, while the cell sheet detached from the surface by lowering the
      temperature to 25 degrees C without using any enzymatic agent.

PMID- 19168189
TI  - Deep gray matter atrophy in multiple sclerosis: a tensor based morphometry.
AB  - Tensor based morphometry (TBM) was applied to determine the atrophy of deep gray
      matter (DGM) structures in 88 relapsing multiple sclerosis (MS) patients. For
      group analysis of atrophy, an unbiased atlas was constructed from 20 normal
      brains. The MS brain images were co-registered with the unbiased atlas using a
      symmetric inverse consistent nonlinear registration. These studies demonstrate
      significant atrophy of thalamus, caudate nucleus, and putamen even at a modest
      clinical disability, as assessed by the expanded disability status score (EDSS).
      A significant correlation between atrophy and EDSS was observed for different DGM
      structures: (thalamus: r=-0.51, p=3.85 x 10(-7); caudate nucleus: r=-0.43, p=2.35
      x 10(-5); putamen: r=-0.36, p=6.12 x 10(-6)). Atrophy of these structures also
      correlated with 1) T2 hyperintense lesion volumes (thalamus: r=-0.56, p=9.96 x
      10(-9); caudate nucleus: r=-0.31, p=3.10 x 10(-3); putamen: r=-0.50, p=6.06 x 10(
      7)), 2) T1 hypointense lesion volumes (thalamus: r=-0.61, p=2.29 x 10(-10);
      caudate nucleus: r=-0.35, p=9.51 x 10(-4); putamen: r=-0.43, p=3.51 x 10(-5)),
      and 3) normalized CSF volume (thalamus: r=-0.66, p=3.55 x 10(-12); caudate
      nucleus: r=-0.52, p=2.31 x 10(-7), and putamen: r=-0.66, r=2.13 x 10(-12)). More
      severe atrophy was observed mainly in thalamus at higher EDSS. These studies
      appear to suggest a link between the white matter damage and DGM atrophy in MS.

PMID- 19168190
TI  - Gray matter atrophy and disability progression in patients with early relapsing
      remitting multiple sclerosis: a 5-year longitudinal study.
AB  - We assessed the relationship between gray matter (GM) and white matter (WM)
      atrophy and clinical status in early relapsing-remitting multiple sclerosis (MS)
      patients over 5 years. A group of 181 patients who participated in the ASA
      (Avonex-Steroid-Azathioprine) study and had complete clinical and MRI assessments
      over 2 and 5 years was investigated. One hundred seventy (170) patients completed
      the 12-month follow-up, 147 the 24-month, 98 the 36-month, 65 the 48-month and 47
      the 60-month. Changes in GM (GMV), WM (WMV) and peripheral GM (PGV) volumes,
      whole brain volume (percentage brain volume change PBVC), lateral ventricle
      volume (LVV), third ventricle width (3VW) and T2-lesion volume (T2-LV) were
      measured. Patients were assigned according to their clinical status to one of two
      groups: the Stable group, and the Reached Confirmed Sustained Progression (RCSP)
      group (24-week interval). At 0-6 months PBVC and GMV, at 0-12 months PBVC, GMV
      and T2-LV, at 0-24 months PBVC and GMV, at 0-36 months PBVC, GMV and T2-LV, and
      at 0-48 PBVC predicted the differences between the RCSP and Stable groups. PBVC
      and LVV showed the strongest ability to differentiate patients who presented 0 or
      >or=3 relapses in the Stable group. Decline in PBVC and GMV were predictive
      markers of disability deterioration. Correlation of T2-LV with clinical status
      was weaker and decreased over time. Higher number of relapses was associated with
      faster decline in whole brain volume.

PMID- 19168191
TI  - Intravenous immunoglobulin treatment for painful sensory neuropathy associated
      with Sjogren's syndrome.
AB  - BACKGROUND: Patients with painful sensory neuropathy associated with Sjogren's
      syndrome-associated neuropathy often show severe neuropathic pain which is not
      relieved by conventional treatments. OBJECTIVE: To evaluate the effect of
      intravenous immunoglobulin (IVIg) therapy in the treatment of neuropathic pain
      associated with Sjogren's syndrome. PATIENTS AND METHODS: We examined 5 patients
      affected by painful sensory neuropathy associated with Sjogren's syndrome. All
      patients were treated with IVIg (0.4 g/kg/day for 5 days) and pain rating was
      assessed by the Visual Analogue Scale (VAS). RESULTS: All five patients showed a
      remarkable improvement in neuropathic pain following IVIg therapy. Pain, assessed
      by the determination of mean VAS score, was reduced by 73.4% from days 2-14
      following treatment. The observed clinical improvement persisted for 2 to 6
      months. One patient, examined by quantitative sensory testing (QST), showed an
      improvement of superficial sensory deficit accompanied by pain relief.
      CONCLUSION: IVIg might be an effective treatment for pain in Sjogren's syndrome
      associated neuropathy. Further studies should be done in a controlled, blind
      study.

PMID- 19168192
TI  - Effects of celecoxib on volumes of hematoma and edema in patients with primary
      intracerebral hemorrhage.
AB  - Celecoxib is a potent anti-inflammatory drug with a safety profile that has been
      well-demonstrated in several human diseases and is reported to have beneficial
      effects in a rat model of intracerebral hemorrhage (ICH). We investigated the
      efficacy and safety of celecoxib treatment in patients with primary ICH. We
      retrospectively collected clinical data of patients admitted within 48 h after
      the onset of primary ICH. We classified the patients administered celecoxib (400
      mg/day) for > or =7 days as the celecoxib-treated group (n=17) and classified the
      patients who were not administered celecoxib as the control group (n=17). The
      volumes of hematoma and edema were analyzed with initial and follow-up (at
      approximately 7 days) brain CT scans. Baseline characteristics, initial severity
      of neurologic sequelae, and initial volumes of the lesions were not different
      between the groups. Celecoxib treatment significantly reduced the volumes of
      edema noted on follow-up brain CT scans as compared with the volumes in the
      control group (30.2+/-17.7 vs. 55.5+/-40.6 mL, p=0.027) and also reduced the
      ratio of initial hematoma and edema volumes vs. the follow-up volumes as compared
      with those of the control group (hematoma, 0.90+/-0.29 vs. 1.54+/-1.12, p=0.035;
      edema, 0.95+/-0.32 vs. 2.08+/-0.88, p<0.001). The incidences of adverse events
      during the admission were not different between the groups. These results suggest
      that celecoxib may be safe and efficacious in patients with primary ICH. To
      confirm this notion, a large-sized prospective study should be performed.

PMID- 19168193
TI  - Balancing the costs and benefits of opioid analgesics in the United States.

PMID- 19168194
TI  - [Cheek paraganglioma: a rare location].
AB  - OBSERVATION: A 29 year-old-woman presented with a massive painless slow-growing
      tumor of the right cheek, with a benign aspect on clinical examination. The CT
      scan with injection, showed a solid-cystic mass, well defined, and partially
      enhanced. The mass was easily removed with a complete endobuccal excision. The
      histological examination and immunohistochemical study revealed a paraganglioma.
      There was no postoperative complication. No recurrence was noted after six months
      of follow-up. DISCUSSION: The paraganglioma is a rare neuroendocrine tumor and
      its location in the cheek has never been reported.

PMID- 19168195
TI  - [The Federation at work].

PMID- 19168197
TI  - A single FLOTAC is more sensitive than triplicate Kato-Katz for the diagnosis of
      low-intensity soil-transmitted helminth infections.
AB  - Accurate diagnostic tools are pivotal for patient management and surveillance of
      helminth control programmes, particularly in the current era of preventive
      chemotherapy. Three consecutive stool samples were obtained from 279
      schoolchildren from Zanzibar, an island where anthelminthic drugs have been
      administered on a large scale for more than a decade. All stool samples were
      examined with the Kato-Katz method. Additionally, one sample per child was
      preserved in sodium acetate-acetic acid-formalin solution, and examined with the
      FLOTAC technique. Considering the pooled results of both methods as diagnostic
      'gold' standard, the observed prevalences of Trichuris trichiura, hookworm and
      Ascaris lumbricoides were 63.4, 35.8 and 22.9%, respectively. The sensitivity of
      examining a single stool sample by FLOTAC for diagnosing T. trichiura, hookworm
      and A. lumbricoides was 88.7, 83.0 and 82.8%, respectively. Lower sensitivities
      were observed for Kato-Katz even after examining three stool samples: 71.8, 46.0
      and 70.3%, respectively. Kato-Katz revealed considerably higher infection
      intensities than FLOTAC. The kappa agreement between a single FLOTAC and
      triplicate Kato-Katz was 0.63 for diagnosing A. lumbricoides and 0.50 for T.
      trichiura, but only 0.30 for hookworm. The high sensitivity of FLOTAC holds
      promise for patient management, monitoring soil-transmitted helminth transmission
      and endpoint(s) of control at the population level.

PMID- 19168196
TI  - [An overview of neurometabolic diseases in Tunisia. a 3-year prospective study].
AB  - INTRODUCTION: Neurometabolic diseases are a large group of genetic diseases. In
      our country, the diagnostic and therapeutic approach to theses diseases is rather
      difficult. The aim of our study was to determine the frequency of neurometabolic
      diseases in the hospital population, to describe the problems in diagnosing these
      conditions and difficulties encountered during patient care. Our goal was to
      propose guidelines for a practical diagnostic and therapeutic approach to
      neurometabolic disorders in our country. METHODS: We have conducted a prospective
      study over a 3-year period including all patients diagnosed with "metabolic
      disease" and followed at the Child and Adolescent Neurology Department of the
      National Institute of Neurology of Tunis. RESULTS: One hundred and thirty-six
      patients were included (2.4% of our patients). Mean age was 7.3 +/- 5.1 years.
      Mean age at onset was 4.3 years. There was a high consanguinity rate. Respiratory
      chain defects were the most frequently suspected diseases (16.9%), followed by
      lysosomal diseases (8.8%). Chromatography, initially systematically prescribed,
      became targeted with a higher diagnostic efficacy. Metabolic diseases diagnosed
      as certain, represented 22% of the studied cases. This can be explained by the
      insufficiency of available laboratory tests of confirmation. The prescription of
      specific treatment was insufficient, even for confirmed pathologies (14.7%)
      because of the high cost of these therapies. CONCLUSION: The diagnostic approach
      has to be rational, targeted, multidisciplinar and conducted within a care
      network. Diagnostic priority should focus on treatable neurometabolic diseases.
      The establishment of a systematized registry and neonatal screening for the main
      treatable neurometabolic diseases constitute the final objective of our work to
      prepare for biochemical and genetic studies.

PMID- 19168198
TI  - Modulation of p53 by mitogen-activated protein kinase pathways and protein kinase
      C delta during avian reovirus S1133-induced apoptosis.
AB  - ARV S1133 infection caused apoptosis in vivo and in vitro; however, the
      intracellular signaling pathways have not been fully delineated. We have
      previously demonstrated that ARV S1133 activates proapoptotic signaling from Src
      to p53, and further investigated how ARV S1133 modulates p53. We found that ARV
      S1133 forms syncytia and induces apoptosis in CEF, DF1 and Vero cells with
      different kinetics. Enhancement of p53 phosphorylation and DNA-binding capacity
      to bax and bad promoters was found in this study to increase bax and bad
      expression in ARV S1133-infected cells. ARV S1133 activates PKC delta and p38 and
      JNK/SAPK pathways, and inhibition of Ras, p38, JNK/SAPK and PKC delta works
      efficiently against apoptosis. Suppression of p38, JNK/SAPK and PKC delta
      selectively abolished ARV S1133-mediated p53 phosphorylation; moreover,
      inhibition of Src did not affect ARV S1133-induced p38 and JNK/SAPK activation,
      whereas blocking of Ras resulted in a reduction in the activities of p38 and
      JNK/SAPK.

PMID- 19168199
TI  - Faecal pollution source identification in an urbanizing catchment using
      antibiotic resistance profiling, discriminant analysis and partial least squares
      regression.
AB  - Increasing urbanisation and changes in land use lead to adverse impacts on the
      quality of natural water resources. The specific sources of contamination are
      often difficult to identify using conventional water quality monitoring
      techniques. This acts as a significant constraint to the development of
      appropriate management techniques to protect natural water resources.
      Consequently, alternative means of identifying pollutant sources and their
      locality are necessary. In this study, Antibiotic Resistance Patterns (ARP) were
      established for a library of 1005 known Escherichia coli source isolates obtained
      from human and non-human (domesticated animals, livestock and wild) sources in an
      urbanizing catchment in Queensland State, Australia. Discriminant Analysis (DA)
      was used to differentiate between the ARP of source isolates and to identify the
      sources of faecal contamination. Partial Least Square (PLS) regression was then
      utilised on identified human source isolates to correlate their locality with
      specified sampling locations within the catchment. The resulting ARP DA indicated
      that a majority of the faecal contamination in the rural areas was non-human.
      However, the percentage of human isolates increased significantly in urbanized
      areas using on site systems for wastewater treatment. The PLS regression was able
      to develop predictive models which indicated a high correlation of human source
      isolates from the urban area. The study results confirm the feasibility of using
      ARP for source tracking faecal contamination in surface waters, as well as
      predicting their point of origin.

PMID- 19168200
TI  - Pulsed electric field treatment for bacteria reduction and its impact on hospital
      wastewater.
AB  - During the last years the pulsed electric field (PEF) method entered several
      fields of application. A promising application is the decontamination of hospital
      wastewater effluents, which are loaded with pathogenic and increasingly with
      antibiotic-resistant bacteria. For this study, Pseudomonas putida suspended in
      buffer solution or wastewater from university hospital was used as reference
      strain. To prove whether the descendent of the survival bacteria develop an
      adaptation to electric field, surviving PEF treated bacteria were recultivated
      and pulsed in serial experiments with 10 pulses (100kVcm(-1) and 600ns pulse
      duration). This procedure was repeated for 30 generations. The inactivation rate
      was calculated with 3.5+/-0.8 log of colony forming units and remained constant
      over 30 cycles. Investigations of the variable intergenic spacer region of the
      ribosomal operon demonstrated no visible changes in this highly variable part of
      the genome structure during the serial PEF treatment experiments. The
      mutagenicity of PEF treated hospital wastewater, buffer solutions and tap water
      was analyzed by the umu-test. Most hospital wastewater samples exhibit a
      considerable genotoxicity already before PEF treatment, but this was not
      increased by the PEF treatment, not even for higher treatments energies over
      250JmL(-1). No genotoxicity was induced in buffer solutions and tap water by PEF
      treatment. This study supports, that PEF treatment is a sustainable non-chemical
      method for bacterial decontamination without any adverse effects.

PMID- 19168201
TI  - Hereditary protein S deficiency from a novel large deletion mutation of the PROS1
      gene detected by multiplex ligation-dependent probe amplification (MLPA).

PMID- 19168202
TI  - Management of large retroperitoneal lipoma in a 12-year-old patient.
AB  - Retroperitoneal lipomas are rare tumors. The etiology of their proliferation is
      uncertain. Metabolic and genetic causes have been reported. We present the case
      of a 12-year-old patient with a large pelvic lipoma causing dysuria and pelvic
      pain. Magnetic resonance imaging revealed the existence of a large
      retroperitoneal fat tumor. Ultrasound-guided fine needle biopsy was performed to
      exclude malignancy. The biopsy specimen revealed tissue consistent with a benign
      lipoma tumor. Exploratory laparotomy revealed a solid lipoma of the
      retroperitoneal space 8 x 6 cm and weighing 300 g. The patient had a good
      postoperative performance status. Lipomas should be considered in the
      differential diagnosis of a solid tumor in the retroperitoneal space.

PMID- 19168203
TI  - Population-based study of biochemical and survival outcomes after permanent 125I
      brachytherapy for low- and intermediate-risk prostate cancer.
AB  - OBJECTIVES: To analyze the biochemical and survival outcomes after permanent low
      dose-rate prostate brachytherapy in a large, consecutive, population-based cohort
      of patients. METHODS: A total of 1006 consecutive implants were performed from
      July 20, 1998 to October 23, 2003 for men with low-risk and "low-tier"
      intermediate-risk prostate cancer. The prescribed minimal peripheral dose was 144
      Gy, using 0.33 mCi (125)I sources and a preplan technique with a strong posterior
      peripheral dose bias. Most patients (65%) had received 6 months of androgen
      deprivation therapy. Supplemental external beam radiotherapy was not used. The
      prognostic features, dose metrics, and follow-up data were prospectively
      collected. Kaplan-Meier and Cox regression analyses were used to assess the
      factors associated with freedom from biochemical recurrence and survival.
      RESULTS: The median patient age at treatment was 66 years. The median follow-up
      was 54 months for biochemical outcomes and 66 months for survival. The actuarial
      freedom from biochemical recurrence rate was 95.6% +/- 1.6% at 5 years and 94.0%
      +/- 2.2% at 7 years. On multivariate analysis, the pretreatment prostate-specific
      antigen level (P = .03) and androgen deprivation therapy use (P = .04) were
      predictive of the freedom from biochemical recurrence. The actuarial rates of
      distant metastasis and disease-specific death at 5 years were both <1%. The
      overall survival rate at 5 years was 95.2% +/- 1.4% and was 93.4% +/- 1.8% at 7
      years. On multivariate analysis, only age was predictive of overall survival (P =
      .011). CONCLUSIONS: When consistently planned and delivered, low-dose-rate
      brachytherapy, without supplemental external beam radiotherapy or intraoperative
      planning, can produce cancer-specific outcomes for men with low- and "low-tier"
      intermediate-risk prostate cancer at least equal to that produced by dose
      escalated external beam radiotherapy or surgical prostatectomy.

PMID- 19168205
TI  - Nuclear matrix protein 22 as adjunct to urine cytology and cystoscopy in follow
      up of superficial TCC of urinary bladder.
AB  - OBJECTIVES: To assess the efficacy of nuclear matrix protein 22 (NMP-22) in the
      diagnosis of recurrent, superficial bladder cancer and whether it can predict for
      future recurrence. METHODS: Patients with diagnosed and treated superficial
      transitional cell carcinoma urinary bladder (Stage Ta, T1, Tis, Nx, and M0)
      presenting for surveillance follow-up were prospectively enrolled in this study
      from February 2004 to August 2005. These patients underwent urine cytology, NMP
      22 testing, and cystopanendoscopy on enrollment in the study. For the next year,
      these patients underwent cystopanendoscopy and cytology at 3-month intervals. The
      ability of NMP-22 to predict for recurrence was determined using the cystoscopy
      findings as the reference standard. RESULTS: A total of 145 patients were
      included in the study. Of these, 56 had recurrence at enrollment. Of the 56
      patients, 48 had positive NMP-22 findings and 22 had positive urine cytology
      findings. The sensitivity, specificity, positive predictive value, and negative
      predictive value was 85.7%, 77.5%, 70.6%, and 89.6%, respectively, for NMP-22
      alone and 92.9%, 75.3%, 70.3%, and 94.4%, respectively, when the cytology and NMP
      22 findings were combined. During the subsequent follow-up of 1 year, 61
      recurrences developed in 47 patients. Cox regression analysis showed that those
      with positive NMP-22 had a 9.57 times greater risk of recurrence during 1 year
      compared with those with negative NMP-22. CONCLUSIONS: The results of our study
      have shown that the addition of NMP-22 testing to cytology increases the
      sensitivity for recurrence detection in patients with superficial transitional
      cell bladder cancer. Patients with positive NMP-22 findings developed
      significantly more recurrences compared with those with negative NMP-22 findings.

PMID- 19168204
TI  - Diabetes-induced alternations in biomechanical properties of urinary bladder wall
      in rats.
AB  - OBJECTIVES: To determine whether diabetes mellitus and the associated changes in
      bladder function will trigger bladder wall tissue remodeling and concomitant
      alterations in the mechanical properties. We investigated the time course of
      changes in function and mechanical properties of diabetic and diuretic rat
      bladders using both in vivo and in vitro techniques METHODS: Cystometry was
      performed at 2, 4, and 8 weeks on female Sprague-Dawley rats that had received
      either a single injection of streptozotocin (65 mg/kg intraperitoneally) or 5%
      sucrose in drinking water for the duration of the experiments. At each point, the
      biaxial mechanical properties of 10 x 10-mm tissue specimens obtained from the
      posterior part of bladder wall were quantified. The changes in overall tissue
      compliance and mechanical anisotropy as a function of time were examined RESULTS:
      Both diabetic and diuretic conditions led to increases in bladder weight, bladder
      capacity, and in vivo compliance compared with the controls at all points tested.
      Under biaxial loading, all bladder wall tissues exhibited a nonlinear stress
      strain relationship and mechanical anisotropy, with greater tissue compliance in
      the circumferential direction than in the longitudinal direction. Although the
      compliance of the bladder wall increased progressively and synchronously in both
      diabetic and diuretic bladders for < or = 4 weeks, only the diabetic bladders
      continued to increase the compliance for < or = 8 weeks (diabetic 0.64 +/- 0.04
      vs diuretic 0.48 +/- 0.05, P = .03) CONCLUSIONS: The results of our study have
      shown that diuresis mainly contributes to the "early" changes of mechanical
      properties of the bladder, with diabetes inducing additional "late" changes of
      mechanical properties of the rat bladders after 4 weeks.

PMID- 19168206
TI  - Minimally invasive comprehensive surgical staging for endometrial cancer:
      Robotics or laparoscopy?
AB  - OBJECTIVE: To compare outcomes between robotic versus laparoscopic hysterectomy
      and lymphadenectomy in patients with endometrial cancer. METHODS: A cohort study
      was performed by prospectively identifying all patients with clinical stage I or
      occult stage II endometrial cancer who underwent robotic hysterectomy and
      lymphadenectomy from 2006-2008 and retrospectively comparing data using the same
      surgeons' laparoscopic hysterectomy and lymphadenectomy cases from 1998-2005,
      prior to our robotic experience. Patient demographics, operative times,
      complications, conversion rates, pathologic results, and length of stay were
      analyzed. RESULTS: 181 patients (105 robotic and 76 laparoscopic) met inclusion
      criteria. There was no significant difference between the two groups in median
      age, uterine weight, bilateral pelvic or aortic lymph node counts, or
      complication rates in patients whose surgeries were completed minimally
      invasively. Despite a higher BMI (34 vs. 29, P<0.001), the estimated blood loss
      (100 vs. 250 mL, P<0.001), transfusion rate (3% vs. 18%, RR 0.18, 95%CI 0.05
      0.64, P=0.002), laparotomy conversion rate (12% vs. 26%, RR 0.47, 95%CI 0.25
      0.89, P=0.017), and length of stay (median: 1 vs. 2 nights, P<0.001) were lower
      in the robotic patients compared to the laparoscopic cohort. The odds ratio of
      conversion to laparotomy based on BMI for robotics compared to laparoscopy is
      0.20 (95% CI 0.08-0.56, P=0.002). The mean skin to skin time (242 vs. 287 min,
      P<0.001) and total room time (305 vs. 336 min, P<0.001) was shorter for the
      robotic cohort. CONCLUSION: Robotic hysterectomy and lymphadenectomy for
      endometrial carcinoma can be accomplished in heavier patients and results in
      shorter operating times and hospital length of stay, a lower transfusion rate,
      and less frequent conversion to laparotomy when compared to laparoscopic
      hysterectomy and lymphadenectomy.

PMID- 19168207
TI  - BRCA1 and implications for response to chemotherapy in ovarian cancer.
AB  - OBJECTIVES: Treatment of epithelial ovarian cancer (EOC) remains a challenge,
      despite advances in surgery and chemotherapy. Hereditary ovarian cancer is
      primarily due to germline mutations in the BRCA1 tumour suppressor gene. In
      addition, sporadic EOC tumours display significant of loss of BRCA1 function due
      to epigenetic inactivation of the BRCA1 gene. This article reviews the
      preclinical and clinical evidence to support a role for BRCA1 as a potential
      predictive biomarker of response to both platinum and taxane based chemotherapy
      in EOC. METHODS: We conducted a Medline and Pubmed search for reports between
      1990 and 2008 using the search terms: BRCA1 and hereditary ovarian cancer, BRCA1
      and sporadic ovarian cancer, ovarian cancer and chemotherapy, ovarian cancer and
      taxanes, ovarian cancer and platinums, ovarian cancer and clinical response,
      BRCA1 and DNA damage, BRCA1 and DNA repair, BRCA1 and mitotic checkpoint. If
      reports identified by these criteria referred to other papers not in the initial
      search, then these were also reviewed if relevant to BRCA1 and ovarian cancer.
      RESULTS: The BRCA1 pathway plays a significant role in the development of both
      hereditary and sporadic EOC. Evidence suggests that BRCA1 is a potential
      biomarker of response to platinum chemotherapy in EOC with BRCA1 deficiency
      predicting for enhanced response. In contrast, initial evidence suggests that
      loss of BRCA1 function results in reduced response to antimicrotubule-based
      chemotherapy. The ability of BRCA1 to differentially modulate response to these
      agents involves loss of BRCA1 mediated DNA repair and mitotic checkpoint control,
      respectively. CONCLUSIONS: Standard first line treatment of EOC consists of a
      combination of platinum and taxane chemotherapy, however clinically useful
      biomarkers for predicting response to these agents have yet to be established.
      BRCA1 may prove useful as a biomarker in EOC for assigning chemotherapy
      treatments based on the presence or absence of BRCA1 function.

PMID- 19168208
TI  - Experimentally induced depletion of germ cells in sub-adult Patagonian pejerrey
      (Odontesthes hatcheri).
AB  - Germ cell (GC) transplantation (GCT) is a novel reproductive technology with
      application in seed production and conservation of endangered species. This study
      examined the suitability of treatment with Busulfan, a cytotoxic agent, and warm
      water, known to cause GC degeneration, for depletion of endogenous GCs in sub
      adult Patagonia pejerrey Odontesthes hatcheri intended as hosts in GCT. In two
      experiments, fish were treated with six combinations of temperature (intermediate
      and high, 20 and 25 degrees C, respectively) and Busulfan (0, 20, and 40 mg/kg
      body weight), given intraperitoneally (ip) as a single (0 week) or repeated (0
      and 4 week) dose. The effectiveness of the treatments was assessed by gonado
      somatic index, histology, and (germ cell-specific) vasa gene expression after 8
      weeks. Fish were allowed to recover at 17 degrees C for 4-8 weeks after the
      treatments to ascertain the permanency of the effects. The high temperature (25
      degrees C) alone induced only incipient gonadal degeneration and germ cell loss,
      but was highly effective in combination with double administration of 40 mg/kg
      Busulfan. Males tolerated Busulfan better and were more easily depleted of germ
      cells than females. Animals treated for 8 weeks were severely devoid of germ
      cells, but were still capable of gametogenesis. Thus, the combination of Busulfan
      and high water temperature appeared to be efficient for depletion of GCs in adult
      fish; and the treated gonads retained the ability to support GC proliferation and
      differentiation. Furthermore, quantitative analysis of vasa transcript levels was
      found to be an useful to monitor the degree of gonad sterility during treatment.

PMID- 19168209
TI  - Pregnancies established from handmade cloned blastocysts reconstructed using skin
      fibroblasts in buffalo (Bubalus bubalis).
AB  - Handmade cloning (HMC), a simple, micromanipulation-free cloning technique, has
      been applied for the production of cloned embryos and offspring in many livestock
      species. The objective of the present study was to compare the effect of donor
      cell type on developmental competence of HMC embryos and to explore the
      possibility of establishing pregnancies using these embryos in buffalo. After
      technical optimization of the HMC procedure for in vitro development of cloned
      blastocysts, various donor cells were compared for their developmental
      efficiency. Using buffalo fetal-, newborn-, adult fibroblasts and cumulus cells,
      blastocyst production rates obtained from reconstructed embryos were 24.0+/-1.8%
      (35/145), 33.0+/-8.0% (56/163), 21.0+/-9.3% (29/133) and 49.6+/-1.9% (77/154),
      respectively. Blastocyst rates were higher (P<0.05) in cumulus cell reconstructed
      embryos in comparison to those derived from fetal or adult fibroblasts. Pregnancy
      diagnosis (transrectal ultrasonography) was carried out at Day 40 of gestation.
      Following transfer of HMC embryos reconstructed using newborn fibroblasts 25%
      (2/8) buffaloes were pregnant and are at Days 201 and 94 of gestation, whereas
      after transfer of HMC embryos reconstructed using fetal fibroblasts, 20% (1/5)
      buffaloes were pregnant and are at Day 73 of gestation. In conclusion, HMC could
      be a simple and efficient technique for the production of cloned embryos for
      establishing pregnancies in buffalo.

PMID- 19168210
TI  - Alcohol-use disorders.
AB  - Alcohol dependence and alcohol abuse or harmful use cause substantial morbidity
      and mortality. Alcohol-use disorders are associated with depressive episodes,
      severe anxiety, insomnia, suicide, and abuse of other drugs. Continued heavy
      alcohol use also shortens the onset of heart disease, stroke, cancers, and liver
      cirrhosis, by affecting the cardiovascular, gastrointestinal, and immune systems.
      Heavy drinking can also cause mild anterograde amnesias, temporary cognitive
      deficits, sleep problems, and peripheral neuropathy; cause gastrointestinal
      problems; decrease bone density and production of blood cells; and cause fetal
      alcohol syndrome. Alcohol-use disorders complicate assessment and treatment of
      other medical and psychiatric problems. Standard criteria for alcohol dependence
      the more severe disorder-can be used to reliably identify people for whom
      drinking causes major physiological consequences and persistent impairment of
      quality of life and ability to function. Clinicians should routinely screen for
      alcohol disorders, using clinical interviews, questionnaires, blood tests, or a
      combination of these methods. Causes include environmental factors and specific
      genes that affect the risk of alcohol-use disorders, including genes for enzymes
      that metabolise alcohol, such as alcohol dehydrogenase and aldehyde
      dehydrogenase; those associated with disinhibition; and those that confer a low
      sensitivity to alcohol. Treatment can include motivational interviewing to help
      people to evaluate their situations, brief interventions to facilitate more
      healthy behaviours, detoxification to address withdrawal symptoms, cognitive
      behavioural therapies to avoid relapses, and judicious use of drugs to diminish
      cravings or discourage relapses.

PMID- 19168211
TI  - Limited impact of Sargassum muticum on native algal assemblages from rocky
      intertidal shores.
AB  - Invasive species represent a serious threat to natural ecosystems through a range
      of negative effects on native species in the region invaded. The invasive species
      Sargassum muticum has invaded several temperate regions worldwide including the
      Galician rocky shoreline (northwestern Spain) in Western Europe. The main aim of
      this study was to assess if colonization by S. muticum has any effect on native
      algal assemblages by experimental removal of S. muticum. We predicted that in
      those plots where S. muticum plants were removed, the structure of native algal
      assemblages would differ from that in plots where S. muticum plants were
      untouched. In addition, we predicted that the effect of Sargassum removal would
      be more important than other causes of variability at the small scale
      investigated. Results indicated limited impact of S. muticum on native
      assemblages. The impact was only evident on the total number of native taxa and
      two understory morpho-functional groups, filamentous and foliose algae, rather
      than on the entire macroalgal assemblages.

PMID- 19168212
TI  - The influence of extracellular matrix derived from skeletal muscle tissue on the
      proliferation and differentiation of myogenic progenitor cells ex vivo.
AB  - Skeletal muscle relies upon regeneration to maintain homeostasis and repair
      injury. This process involves the recruitment of the tissue's resident stem cell,
      the muscle progenitor cell, and a subsequent proliferative response by newly
      generated myoblasts, which must then align and fuse to generate new muscle
      fibers. During regeneration, cells rely on environmental input for direction.
      Extracellular matrix (ECM) represents a crucial component of a cell's
      microenvironment that aids in guiding muscle regeneration. We hypothesized that
      ECM extracted from skeletal muscle would provide muscle progenitor cells and
      myoblasts with an ideal substrate for growth and differentiation ex vivo. To test
      this hypothesis, we developed a method to extract ECM from the large thigh
      muscles of adult rats and present it to cells as a surface coating. Myogenic
      cells cultured on ECM extract experienced enhanced proliferation and
      differentiation relative to standard growth surfaces. As the methodology can be
      applied to any size muscle, these results demonstrate that bioactive ECM can be
      readily obtained from skeletal muscle and used to develop biomaterials that
      enhance muscle regeneration. Furthermore, the model system demonstrated here can
      be applied to the study of interactions between the ECM of a particular tissue
      and a cell population of interest.

PMID- 19168213
TI  - Convection-enhanced delivery of nanocarriers for the treatment of brain tumors.
AB  - Primary brain tumors have a significant infiltrative capacity as their
      reappearance after resection usually occurs within 2cm of the tumor margin. Local
      delivery method such as Convection-Enhanced Delivery (CED) has been introduced to
      avoid this recurrence by delivering active molecules via positive-pressure
      methods. For an efficient infusion, the distribution volume of the drug has to be
      optimized while avoiding backflow, since this is responsible for side effects and
      a reduction of therapeutic efficacy. The encapsulation of the drug infused in
      nanosized structures can be considered, which would lead to a reduction of both
      toxicity of the treatment and infusion time during CED. In the present review, we
      will firstly discuss the technical approach of CED with regard to catheter design
      and brain characteristics; secondly, we will describe the 'ideal' nanocarrier in
      terms of size, surface properties, and interaction with the extracellular matrix
      for optimal diffusion in the brain parenchyma. We also discuss preclinical and
      clinical applications of this new method.

PMID- 19168214
TI  - The effect of a layer-by-layer chitosan-heparin coating on the endothelialization
      and coagulation properties of a coronary stent system.
AB  - A biomacromolecular layer-by-layer coating process of chitosan/heparin onto a
      coronary stent is designed for the acceleration of the re-endothelialization and
      healing process after coronary stent deployment. The results of in vitro
      culturing of porcine iliac artery endothelial cells as well as the measurements
      of the APTT, PT and TT supported the rationale that the combination of chitosan
      and heparin could bring both endothelial cell compatibility and
      haemocompatibility to the stent surface. A porcine coronary injury model and
      arteriovenous shunt model were used for the further evaluation of the application
      of this kind of surface-modified stainless steel stent in vivo. The final results
      proved that this facile coating approach could significantly promote re
      endothelialization and was safer compared with bare metal stents for its much
      improved anticoagulation property.

PMID- 19168215
TI  - Contact activation of blood-plasma coagulation.
AB  - This opinion identifies inconsistencies in the generally-accepted surface
      biophysics involved in contact activation of blood-plasma coagulation, reviews
      recent experimental work aimed at resolving inconsistencies, and concludes that
      this standard paradigm requires substantial revision to accommodate new
      experimental observations. Foremost among these new findings is that surface
      catalyzed conversion of the blood zymogen factor XII (FXII, Hageman factor) to
      the enzyme FXIIa (FXII [surface] --> FXIIa, a.k.a. autoactivation) is not
      specific for anionic surfaces, as proposed by the standard paradigm. Furthermore,
      it is found that surface activation is moderated by the protein composition of
      the fluid phase in which FXII autoactivation occurs by what appears to be a
      protein-adsorption-competition effect. Both of these findings argue against the
      standard view that contact activation of plasma coagulation is potentiated by the
      assembly of activation-complex proteins (FXII, FXI, prekallikrein, and high
      molecular weight kininogen) directly onto activating surfaces (procoagulants)
      through specific protein/surface interactions. These new findings supplement the
      observation that adsorption behavior of FXII and FXIIa is not remarkably
      different from a wide variety of other blood proteins surveyed. Similarity in
      adsorption properties further undermines the idea that FXII and/or FXIIa are
      distinguished from other blood proteins by unusual adsorption properties
      resulting in chemically-specific interactions with activating anionic surfaces.
      IMPACT STATEMENT: This review shows that the consensus biochemical mechanism of
      contact activation of blood-plasma coagulation that has long served as a
      rationale for poor hemocompatibility is an inadequate basis for surface
      engineering of advanced cardiovascular biomaterials.

PMID- 19168216
TI  - The effect of microstructured surfaces and laminin-derived peptide coatings on
      soft tissue interactions with titanium dental implants.
AB  - In the present study, we investigated the dental implant protection from peri
      implant inflammation by improving the soft tissue adhesion on the titanium
      surface. Porous titanium was used to create, at the level of the transmucosal
      part of the implants (the "neck"), a microstructured 3-dimensional surface that
      would tightly seal the interface between the implant and soft tissue. Cell
      specific adhesion properties were induced via an adhesion peptide derived from
      laminin-5 coupled to native or cross-linked PLL/PGA multilayered polyelectrolyte
      films (MPFs), which are used for biomedical device coatings. Porous titanium
      exhibited good cell-adhesion properties, but the colonisation of the material was
      further improved by a coating with laminin-5 functionalised MPFs and especially
      with (PLL/PGA)(6,5)-PGA-peptide film. Focal contact formation was observed on
      cross-linked architectures, reflecting cell anchorage on these surfaces. In
      contrast, when seeded on laminin-5-functionalised native films, epithelial cells
      formed only very diffuse focal contacts, but adhered via hemidesmosome formation.
      In vivo experiments confirmed that the porous titanium was colonised by cells of
      soft tissue. Altogether, the results indicate that the microstructure of the
      implant neck combined with a specific bioactive coating could constitute
      efficient routes to improve the integration of soft tissue on titanium dental
      implants, which could significantly protect implants from peri-implant
      inflammation and enhance long-term implant stabilisation.

PMID- 19168217
TI  - Differential placental hormone gene expression during pregnancy in a transgenic
      mouse containing the human growth hormone/chorionic somatomammotropin locus.
AB  - The human (h) growth hormone/chorionic somatomammotropin (GH/CS) gene locus
      presents a unique model to gain insight into the molecular mechanisms that have
      allowed a closely related family of genes to be expressed in two distinct cell
      lineages/tissues: pituitary somatotrophs and placental syncytiotrophoblasts.
      However, studies of external factors that regulate gene expression have been
      somewhat limited by (i) a lack of human cell lines expressing endogenous GH or CS
      appropriately; and (ii) the fact that the GH/CS locus is unique to primates and
      thus does not exist in rodents. In the current study, a transgenic (171 h GH/CS
      TG) mouse was generated containing the intact hGH/CS gene cluster and hGH locus
      control region (LCR) in a 171-kilobase DNA fragment. Pituitary and placental
      specific expression of hGH/CS RNA was detected at embryonic day (E) 18.5.
      Immunostaining of hGH was seen in somatotrophs of the anterior pituitary
      beginning in late gestation. The presence of hCS protein was detected in the
      placental labyrinth in trophoblasts functionally analogous to the
      syncytiotrophoblast of the chorionic villi. This pattern of gene expression is
      consistent with the presence of essential components of the hGH/CS LCR.
      Transcript levels for hCS-A, hCS-B and placental hGH-variant increased in 171
      hGH/CS-TG placenta during gestation (E11.5-E18.5), as previously observed in
      human placental development. Throughout gestation, hCS-A RNA levels were
      proportionately higher, accounting for 91% of total CS RNA by E18.5, comparable
      to term human placenta. Finally, the previous correlation between the
      transcription factor AP-2alpha and hCS RNA expression observed in developing
      primary human cytotrophoblast cultures, was extended to pregnancy in the 171
      hGH/CS-TG mouse. The 171 hGH/CS-TG mouse thus provides a model to investigate
      hGH/CS gene expression, including in pregnancy.

PMID- 19168218
TI  - Bone marrow stromal cells attenuate injury-induced changes in galanin, NPY and
      NPY Y1-receptor expression after a sciatic nerve constriction.
AB  - Single ligature nerve constriction (SLNC) of the rat sciatic nerve triggers
      neuropathic pain-related behaviors and induces changes in neuropeptide expression
      in primary afferent neurons. Bone marrow stromal cells (MSCs) injected into the
      lumbar 4 (L4) dorsal root ganglia (DRGs) of animals subjected to a sciatic nerve
      SLNC selectively migrate to the other ipsilateral lumbar DRGs (L3, L5 and L6) and
      prevent mechanical and thermal allodynia. In this study, we have evaluated the
      effect of MSC administration on the expression of the neuropeptides galanin and
      NPY, as well as the NPY Y(1)-receptor (Y(1)R) in DRG neurons. Animals were
      subjected to a sciatic nerve SLNC either alone or followed by the administration
      of MSCs, phosphate-buffered saline (PBS) or bone marrow non-adherent mononuclear
      cells (BNMCs), directly into the ipsilateral L4 DRG. Seven days after injury, the
      ipsilateral and contralateral L4-5 DRGs were dissected out and processed for
      standard immunohistochemistry, using specific antibodies. As previously reported,
      SLNC induced an ipsilateral increase in the number of galanin and NPY
      immunoreactive neurons and a decrease in Y(1)R-positive DRG neurons. The
      intraganglionic injection of PBS or BNMCs did not modify this pattern of
      expression. In contrast, MSC administration partially prevented the injury
      induced changes in galanin, NPY and Y(1)R expression. The large number of Y(1)R
      immunoreactive neurons together with high levels of NPY expression in animals
      injected with MSCs could explain, at least in part, the analgesic effects exerted
      by these cells. Our results support MSC participation in the modulation of
      neuropathic pain and give insight into one of the possible mechanisms involved.

PMID- 19168219
TI  - Hematologic and cytogenetic response to lenalidomide in de novo acute myeloid
      leukemia with chromosome 5q deletion.

PMID- 19168220
TI  - Responsiveness and clinically important differences for the VF-14 index, SF-36,
      and visual acuity in patients undergoing cataract surgery.
AB  - OBJECTIVE: To assess visual acuity (VA) and 2 questionnaires of health-related
      quality of life--the Visual Function 14 (VF-14) index and the Medical Outcomes
      Study Short Form 36 Health Survey (SF-36)--as instruments for capturing
      clinically important changes after cataract surgery. DESIGN: Prospective,
      observational study. PARTICIPANTS: Four thousand three hundred fifty-six
      consecutive patients attending ophthalmologic clinics in 17 hospitals in
      preparation for cataract surgery were recruited. METHODS: Clinical data were
      collected in the visit before the intervention and 6 weeks after surgery by
      ophthalmologists. Patients completed the questionnaires before surgery and 3
      months after surgery. MAIN OUTCOME MEASURES: The VF-14 and SF-36 questionnaire
      results obtained before surgery and 3 months after the procedure and VA before
      the procedure and 6 weeks afterward. RESULTS: Positive mean changes in VA (+0.47)
      and VF-14 results (+24.03) indicated significant improvements after cataract
      surgery that were not reflected in changes in SF-36 domains (from 1.86 to 5.62).
      Responsiveness parameters demonstrated large changes in VA and VF-14 scores but
      not in SF-36 domains. The minimal clinically important differences (MCID) after
      surgery were 0.41 for VA and 15.57 for VF-14 results; the minimal detectable
      change (MDC) for VF-14 was 10.81. CONCLUSIONS: Visual acuity and VF-14 scores,
      but not SF-36 scores, are appropriate instruments for capturing clinically
      important changes after cataract surgery. The MCID and MDC values obtained
      herein, although not absolute thresholds, may aid in the interpretation of
      changes in VA and VF-14 scores.

PMID- 19168221
TI  - Complement component C3 and risk of age-related macular degeneration.
AB  - OBJECTIVE: To explore the association between polymorphisms in the complement
      component 3 (C3) gene and age-related macular degeneration (AMD), and to
      investigate the modifying effect of complement factor H (CFH) Y402H, LOC387715
      A69S and smoking. DESIGN: Pooled data from the prospective, population-based
      Rotterdam Study (enrolment between 1990 and 1993, and 3 follow-up examinations
      between September 1, 1993, and December 31, 2004) and an independent case-control
      study from the Netherlands. PARTICIPANTS: The Rotterdam Study comprised a total
      of 6418 persons aged >or=55 years who had gradable fundus photographs. The case
      control study consisted of 357 unrelated AMD patients and 173 control individuals
      aged >or=55 years. METHODS: The variants R102G and P314L of the C3 gene, CFH
      Y402H and LOC387715 A69S, were genotyped in all study participants. Information
      on cigarette smoking was obtained by interview at baseline. MAIN OUTCOME
      MEASURES: Early and late stages of prevalent and incident AMD, graded according
      to the international classification and grading system for AMD. RESULTS: We found
      a population frequency of 0.217 for R102G and 0.211 for P314L in the Rotterdam
      Study. Both alleles significantly increased the risk of early AMD and all
      subtypes of late AMD, and this risk seemed to be independent of CFH Y402H,
      LOC387715 A69S, and smoking. Detailed analysis showed that the haplotype carrying
      both alleles had the highest frequency difference between cases and controls
      (P=0.006). We estimated a total population-attributable risk of 14.6%. A meta
      analysis of all currently available data yielded a pooled odds ratio (OR) of 1.61
      (95% confidence interval [CI], 1.46-1.78) for the R102G allele, and an OR of 1.50
      (95% CI, 1.31-1.71) for the P314L allele. CONCLUSIONS: Our study showed a
      significant association between variants in the C3 gene and AMD and further
      highlights the crucial role of the complement pathway in the etiology of AMD.

PMID- 19168222
TI  - Prevalence of diabetic retinopathy in rural China: the Handan Eye Study.
AB  - PURPOSE: To describe the age- and gender-specific prevalence, characteristics,
      and severity of diabetic retinopathy (DR) in a rural population in northern
      China. DESIGN: A population-based cross-sectional study. PARTICIPANTS: A total of
      6830 Han Chinese aged 30 years and older from 13 villages of Yongnian County,
      Handan City, Hebei Province, China. METHODS: All participants underwent a
      standardized interview, a comprehensive eye examination, and fasting blood
      glucose testing according to the American Diabetes Association diagnostic
      criteria (fasting plasma glucose >or=7.0 mmol/l). Retinal photographs obtained
      after pupil dilation were graded for the presence and severity of DR according to
      the modified Early Treatment Diabetic Retinopathy Study classification system.
      MAIN OUTCOME MEASURES: Any DR, retinopathy grades, macular edema, or vision
      threatening retinopathy. RESULTS: Of the 6830 eligible individuals participating
      in the study, 5597 (81.9%) had fasting blood glucose results available. Of these,
      387 participants (6.9%) were diagnosed with diabetes mellitus, including 247
      subjects with new diabetes mellitus (NDM) and 140 subjects with known diabetes
      mellitus (KDM). For these, gradable photographs were available for 368 subjects
      (95.1%). The overall prevalence of DR was 43.1% (95% confidence interval, 38.1
      48.4) and was higher in persons with KDM (65.2%) than NDM (33.5%). The prevalence
      of proliferative DR, macular edema, and vision-threatening retinopathy was 1.6%,
      5.2%, and 6.3%, respectively, with 12.1% with KDM having untreated vision
      threatening DR. No age- or gender-related differences were present. The
      prevalence of DR was strongly related to duration of disease. CONCLUSIONS: Our
      study reports a high prevalence of DR among adults 30 years and older with
      diabetes in rural China. On the basis of estimates obtained from our study, we
      projected that in rural China, 21.1 million persons aged 30+ years have diabetes
      and 9.2 million have DR, including 1.3 million with vision-threatening DR. There
      is a pressing need for appropriate screening and management of diabetes and its
      complications in rural China.

PMID- 19168223
TI  - Nasal retinal nerve fiber layer attenuation: a biomarker for vigabatrin toxicity.
AB  - PURPOSE: To investigate whether nasal peripapillary retinal nerve fiber layer
      (RNFL) attenuation is associated with visual field loss attributed to the anti
      epileptic drug vigabatrin. DESIGN: Prospective cross-sectional observational
      study. PARTICIPANTS: Twenty-seven individuals with focal-onset epilepsy exposed
      to vigabatrin and 13 individuals with focal-onset epilepsy exposed to non
      GABAergic anti-epileptic drug monotherapy. METHODS: At one visit, suprathreshold
      perimetry of the central and peripheral field (3-zone, age-corrected Full Field
      135 Screening Test) and threshold perimetry of the central field (Program 30-2
      and the FASTPAC strategy) were undertaken using the Humphrey Field Analyzer (Carl
      Zeiss Meditech, Dublin, CA). At a second visit, ocular coherence tomography was
      undertaken for the right eye using the 3.4 RNFL thickness protocol of the
      StratusOCT (Carl Zeiss Meditech). MAIN OUTCOME MEASURES: The magnitude, for each
      individual, of the RNFL thickness, averaged across the 4 oblique quadrants, and
      for each separate quadrant. RESULTS: Of the 27 individuals exposed to vigabatrin,
      11 (group I) exhibited vigabatrin-attributed visual field loss, 15 exhibited a
      normal field, and 1 exhibited a homonymous quadrantanopia (group II). All 13
      individuals exposed to non-GABAergic therapy had normal fields (group III). All
      individuals in group I exhibited abnormal average and nasal quadrant RNFL
      thicknesses in the presence of a normal temporal quadrant thickness. Most also
      exhibited additional RNFL attenuation in either the superior or inferior
      quadrant, or both. Four individuals in group II exhibited an identical pattern of
      RNFL attenuation suggesting that nasal RNFL thinning is a more sensitive marker
      for vigabatrin toxicity than visual field loss. None of the 13 individuals in
      group III exhibited nasal quadrant RNFL attenuation. CONCLUSIONS: Vigabatrin
      attributed visual field loss is associated with a characteristic pattern of RNFL
      attenuation: nasal quadrant thinning and normal temporal quadrant thickness with,
      or without, superior or inferior quadrant involvement. Nasal attenuation may
      precede visual field loss. Ocular coherence tomography of the peripapillary RNFL
      should be considered in patients previously exposed to vigabatrin. It should also
      be considered at baseline and follow-up in those commencing vigabatrin for
      treatment of epilepsy or in trials for anti-addiction therapy. The pattern of
      RNFL thinning seems to be a useful biomarker to identify vigabatrin toxicity.

PMID- 19168224
TI  - Life events, coping and depressive symptoms among young adolescents: a one-year
      prospective study.
AB  - BACKGROUND: To investigate prospectively over one year, the extent to which
      greater exposure to negative life events, greater use of more negative coping
      strategies, and less use of positive coping strategies and an optimistic thinking
      style, predicts the onset of depressive symptoms among adolescents. METHODS: A
      prospective longitudinal study of 5,634 adolescents (Mean Age=13.1, SD=0.5)
      enrolled in Year 8 at secondary school. Standard questionnaires were used to
      assess depressive symptoms and the predictor variables. RESULTS: Over a one-year
      period, there was an independent and statistically significant relationship
      between transition to a CES-D score above the recommended cut-off score and i)
      greater exposure to negative life events and use of negative coping strategies,
      and ii) less use of positive coping strategies and an optimistic thinking style.
      Among males who experienced a higher number of negative life events, the impact
      on depressive symptoms was greater among those who made more use of negative
      coping strategies. LIMITATIONS: Self-report questionnaires completed by
      adolescents were employed to evaluate all the variables in the study. Only two
      assessment points were available. Ten percent of adolescents did not complete the
      follow-up assessment. CONCLUSIONS: Particularly among females, early adolescence
      is marked by increased susceptibility to depressive symptoms. Helping young
      adolescents to adopt more positive coping strategies and optimistic thinking
      styles may reduce their risk for the onset of depressive symptoms. This may be
      particularly important for young males who experience high levels of adverse life
      events and utilise negative coping strategies.

PMID- 19168225
TI  - Criminal behaviour and violent crimes in former inpatients with affective
      disorder.
AB  - BACKGROUND: Several studies have reported criminal and violent behaviour in
      people with schizophrenia but few have investigated the association between
      affective disorders and violent behaviour. METHODS: We reviewed the national
      crime register for records of criminal offences committed by 1561 patients with
      affective disorders treated between 1990 and 1995 in the Psychiatric Hospital of
      the University of Munich. The sample was divided into patients with bipolar I
      disorder, manic disorder and major depressive disorder. Sociodemographic and
      other risk factors for non-violent and violent criminal behaviour were analysed.
      RESULTS: Sixty-five (4.16%) patients had been convicted in the 7 to 12 years
      after discharge (307 cases). The rate of criminal behaviour and violent crimes
      was highest in the manic disorder group: 15.7% (14 of 89) were listed in the
      national crime register and 5.6% (5 of 89) were convicted of physical injury
      offences. Violence and criminality were comparatively rare in patients with major
      depressive disorder: only 1.42% (10 of 702) committed violent crimes. Male gender
      was a substantial risk factor for non-violent and especially violent behaviour:
      the rate of violent crimes was six times higher than in females. Marital status
      appeared to influence the prevalence of later delinquency: separated, divorced
      and widowed patients committed offences more frequently. A history of substance
      use problems before clinical treatment was reported by 21.2% (329 of 1561) of the
      sample. A wide range of different crimes were committed, with defalcation, theft
      and fraud being the most frequent. Twenty-one cases of physical assault and one
      case of later homicide were recorded. In contrast to other forensic studies, we
      did not find a significant effect of substance abuse on the risk of later
      delinquent behaviour. CONCLUSION: The frequency of criminal behaviour and violent
      crimes in individuals with affective disorder depends on much more than just the
      diagnosis. This study may stimulate further research to identify
      psychopathological predictors for future violent and criminal behaviour.

PMID- 19168226
TI  - Depression symptoms and hypothyroidism in a population-based study of middle-aged
      Brazilian women.
AB  - BACKGROUND: Overt hypothyroidism is often recognized as an important cause of
      depression, but in sub-clinical cases, results are inconsistent and most prior
      studies have involved small samples. METHODS: We evaluated the association
      between hypothyroidism and depressive symptoms (PRIME-MD) in a population-based
      study of 1298 middle-aged women living in a large metropolitan city in Brazil.
      RESULTS: 45.7% presented depressive symptoms, and 12.3% presented hypothyroidism.
      Multiple logistic regression analysis adjusting for age, race, smoking and body
      mass index showed that women with TSH>10 mUI/ml had a threefold chance of
      presenting depressive symptoms compared to those with normal levels of TSH. Among
      those with clinical hypothyroidism the adjusted OR was 8.7. CONCLUSION: High
      levels of TSH were associated to an increased chance of developing depression in
      the general population. Therefore, depressive symptoms must be considered in
      patients with thyroid dysfunction and depressed patients should be tested for
      TSH.

PMID- 19168227
TI  - Selective attention biases of people with depression: positive and negative
      priming of depression-related information.
AB  - Selective attention biases are believed to be one of the cognitive
      vulnerabilities to depression. This study examined two types of attention biases,
      namely attention facilitation and attention disinhibition, towards mood-congruent
      words in 40 clinically depressed outpatients and 40 never-depressed healthy
      controls. Measures were differential reaction time towards neutral and depressive
      words in the positive and negative priming paradigms that were used to assess
      attention facilitation and attention disinhibition, respectively. Results showed
      that the depressed group exhibited enhanced attention facilitation to depressive
      words relative to neutral words, whereas the control group did not. The
      differential reduction of reaction time of the depressed group to the previously
      presented depressive words relative to the previously presented neutral words was
      greater than that in the control group. On the other hand, both groups showed
      similar attention disinhibition to depressive words relative to neutral words.
      The differential increase in reaction time to previously ignored depressive words
      relative to the previously ignored neutral words was similar in both groups. The
      above results suggest that major depressive disorder is characterized by
      attention facilitation by mood-congruent information, but inhibition difficulties
      in attention to depression-related information is not specific to depressive
      disorder.

PMID- 19168228
TI  - A structural equation model of depression and the defense system factors: a
      survey among Chinese college students.
AB  - Questionnaires were administered to a large sample of subjects (1363 Chinese
      college students), to evaluate the mediating risk factors in the defense system
      of depression, including personality, coping skills, interpersonal context and
      family environment. Structural equation modeling (SEM) was used to analyze a
      total of 12 variables in order to understand how they interact with each other.
      Eysenck's Neuroticism, Extraversion, and Psychoticism personality types act as
      the essential parts of the model, both directly and indirectly impacting
      depression. Coping styles are the mediators that regulate the effects of
      personality and family environment on depression. Family environment has only
      indirect effects through personality and positive coping style. Interpersonal
      context may not have had a significant correlation with depression, but was
      influenced by family environment and had a correlation with positive coping
      style. According to the results, therapies based on personality adjustment,
      family environment and coping styles of college students are greatly recommended
      among college students in order to lessen the chances of or to prevent
      depression. The present results may advance our understanding of depression
      etiology in young Chinese adults and provide suggestions of factors that should
      be taken into account in the evaluation, treatment and even the prevention of
      depression.

PMID- 19168229
TI  - Neuropsychiatric manifestations of systemic lupus erythematosus - A primary
      disease manifestation.

PMID- 19168230
TI  - Otomicroscope in the emergency department management of pediatric ear foreign
      bodies.
AB  - OBJECTIVE: To determine the effect of a dedicated otomicroscope in the emergency
      department (ED) management of complex ear foreign bodies (FB). METHODS:
      Prospective analysis of 85 patients with complex pediatric ear FB's. RESULTS: 65
      (76%) of 85 FB's were successfully removed in the ED. 54 (63%) had previous
      attempted removal, 27 (31%) were less than age 4, 37 (44%) had ear FB's present
      longer than 24h, 3 (4%) had multiple ear FB's, and 9 (11%) had an external
      auditory canal (EAC) comorbidity prior to attempted removal. 31 (36%) were
      touching the tympanic membrane (TM). 20 (23%) had complications with removal with
      EAC laceration most common and no TM perforations or hematomas. Mean and median
      number of attempts for removal was 1.65 and 1.0. Successful removal was
      associated with the location of the FB, presence of an EAC comorbidity, and
      number of attempts (p<0.05). Complication rate was associated with an EAC
      comorbidity and number of attempts (p<0.05). EAC comorbidity was more common in
      FB's touching the TM (p<0.05). Increased number of attempts was associated with
      use of sedation (p<0.05). CONCLUSIONS: The implementation of an otomicroscope
      into the ED resulted in successful removal of complex pediatric ear FB's with few
      attempts and a low rate of serious complications.

PMID- 19168231
TI  - Comparison of head rotation versus head elevation methods for vestibular evoked
      myogenic potentials by using logon stimulus.
AB  - OBJECTIVES: To compare vestibular evoked myogenic potentials (VEMP) between two
      different methods, head rotation (HR) with unilateral recording and head
      elevation (HE) with bilateral simultaneous recording. SUBJECTS AND METHODS:
      Twenty-eight healthy children (56 ears) were involved in the study. The subjects
      were tested in two different positions: head rotation (HR) method and head
      elevation (HE) method. Right- and left-side recordings were made separately in HR
      method and simultaneously in HE method. Logon type stimulus with 120dB Hl
      intensity was used to trigger VEMPs in both methods. RESULTS: The response rate
      was 80.4% for HR method and 89.3% for HE method (p>0.05). There was no
      significant difference between the two groups with respect to P1 latency, N1
      latency, and P1-N1 interval. The mean P1-N1 amplitude of HE method was higher
      than HR method (p<0.05). There were very strong positive correlations between two
      methods regarding N1 latency and P1-N1 interval (r: 0.849 and 0.841,
      respectively). CONCLUSION: Bilateral simultaneous VEMP recording in head
      elevation position by using logon stimulus is a practical way to evaluate
      vestibulocollic reflex in children and it gives superior results than unilateral
      recording with head rotation position.

PMID- 19168232
TI  - Comparison of three statistical methods for analysis of fall predictors in people
      with dementia: negative binomial regression (NBR), regression tree (RT), and
      partial least squares regression (PLSR).
AB  - Searching for background factors associated with falls in people with dementia is
      difficult because the population is heterogeneous. The aim of this study was to
      compare the efficacies of three statistical methods for analysis of fall
      predictors in people with dementia. NBR, RT and PLSR analyses were compared. Data
      used for the comparison were from a prospective cohort study of 192 patients at a
      psychogeriatric ward, specializing in patients with cognitive impairment and
      related behavioral and psychological symptoms. Seventy-eight of these patients
      fell a total of 238 times. PLSR and RT analyses are directed at finding patterns
      among predictor variables related to outcome, whereas an NBR model is directed at
      finding predictor variables that, independent of other variables, are related to
      the outcome. The NBR analysis explained an additional 10-15% variation compared
      with the PLSR and RT analyses. The results of PLSR and RT show a similar
      plausible pattern of predictor variables. However, none of these techniques
      appears to be sufficient in itself. In order to gain patterns of explanatory
      variables, RT would be a good complement to NBR for analysis of fall predictors.

PMID- 19168233
TI  - Are oxygen uptake kinetics in chronic heart failure limited by oxygen delivery or
      oxygen utilization?
AB  - BACKGROUND: The delay in O(2) uptake kinetics during and after submaximal
      physical activity (O(2) onset and recovery kinetics, respectively) correlates
      well with the functional capacity of patients with chronic heart failure (CHF).
      This study examined the physiological background of this delay in moderately
      impaired CHF patients by comparing kinetics of cardiac output (Q) and O(2) uptake
      (V(O(2))). METHODS: Fourteen stable CHF patients (New York Heart Association
      class II-III) and 8 healthy subjects, matched for age and body mass index, were
      included. All subjects performed a submaximal constant-load exercise test to
      assess O(2) uptake kinetics. Furthermore, in 10 CHF patients Q was measured by a
      radial artery pulse contour analysis method, which enabled the simultaneous
      modelling of exercise-related kinetics of Q and V(O(2)). RESULTS: Both O(2) onset
      and recovery kinetics were delayed in the patient group. There were no
      significant differences between the time constants of Q and V(O(2)) during
      exercise-onset (62+/-25 s versus 59+/-28 s, p=0.51) or recovery (61+/-25 s versus
      57+/-20 s, p=0.38) in the patient group, indicating that O(2) delivery was not in
      excess of the metabolic demands in these patients. CONCLUSION: The delay in O(2)
      onset and recovery kinetics in moderately impaired CHF patients is suggested to
      be due to limitations in O(2) delivery. Therefore, strategies aimed at improving
      exercise performance of these patients should focus more on improvements of O(2)
      delivery than on O(2) utilization.

PMID- 19168234
TI  - Aldosterone levels and stroke incidence in essential hypertensive patients.

PMID- 19168235
TI  - The effects of coffee intake on coronary heart disease: ongoing controversy.

PMID- 19168236
TI  - Sympathetic overactivity and sudden cardiac death among hemodialysis patients
      with left ventricular hypertrophy.
AB  - BACKGROUND: We prospectively investigated whether cardiac autonomic imbalance is
      associated with sudden cardiac death (SCD) among a group of hemodialysis patients
      with left ventricular hypertrophy (LVH). METHODS: In a prospective cohort study,
      we enrolled 196 asymptomatic patients on chronic hemodialysis who had LVH as
      determined by echocardiography and had undergone twenty-four-hour ambulatory
      Holter electrocardiography between dialysis sessions (males/females, 114/82; mean
      age, 65+/-12 years) to analyze heart rate variability. We calculated the
      percentage difference between adjacent NN intervals more than 50 ms (pNN50) and
      high-frequency component (HF, 0.15-0.40 Hz) as parameters of cardiac
      parasympathetic activity, and the low-frequency component (LF, 0.04-0.15 Hz)/HF
      component ratio as a parameter of sympathetic activity. RESULTS: During 4.5+/-1.9
      year follow-up, 21 patients who had undergone coronary revascularization within
      60 days of enrollment were excluded from the analysis. Among the remaining 175
      patients (male/female, 105/70; 66+/-12 years), SCD was recognized in 23 patients.
      On stepwise Cox hazard analysis, SCD was positively associated with age and LF/HF
      ratio, and tended to be inversely associated with pNN50. On Kaplan-Meier
      analysis, SCD-free survival rates at 5 years were 29.4% and 98.1% in patients
      with LF/HF ratios of 1.9 or more and below 1.9, respectively. CONCLUSIONS: The
      presence of cardiac sympathetic overactivity may predict the occurrence of SCD in
      the asymptomatic hemodialysis patients with LVH.

PMID- 19168237
TI  - Endothelial dysfunction, ADMA and insulin resistance in essential hypertension.
AB  - BACKGROUND: Endothelial dysfunction and insulin resistance (IR) are associated
      with essential hypertension and other cardiovascular risk factors. Asymmetric
      dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase,
      induces endothelial dysfunction in different setting of patients. However, at
      this moment no data are available about the role of ADMA and IR to induce
      endothelial dysfunction in an independent way or combined between them. In this
      study, we investigated, in 63 hypertensives and 21 normotensive healthy subjects,
      the relationship between ADMA and IR and their possible interaction on
      endothelial function. METHODS: ADMA plasma levels were measured by high
      performance liquid chromatography, and IR by homeostasis model assessment (HOMA).
      Endothelial function was estimated by intra-arterial infusion of acetylcholine
      (ACh) and sodium nitroprusside at increasing doses. RESULTS: Hypertensive
      patients had significantly higher ADMA, insulin, HOMA and C-reactive protein
      (CRP) values than normotensive controls (P<0.0001). There were no significant
      differences in mean l-arginine/ADMA ratio between groups. ACh-stimulated forearm
      blood flow (FBF) was significantly reduced in hypertensive patients (P<0.0001).
      In hypertensive group, HOMA was the strongest determinant of FBF, accounting for
      the 45.5% of its variation. ADMA and gender were the independent determinants of
      HOMA, accounting for 12.3% and 8.3% of its variation, respectively. CONCLUSIONS:
      The association between ADMA and IR contributes to identify a possible novel
      mechanism by which ADMA promotes vascular damage, increasing individual
      cardiovascular risk in hypertensive patients. However, this hypothesis should be
      tested in a larger study group.

PMID- 19168238
TI  - Campylobacter jejuni: enterocolitis and myopericarditis.
AB  - Campylobacter jejuni enteritis is the commonest enteric infection in the
      developed world. There are only few reported cases in the medical literature of
      cardiac complications associated with C. jejuni enterocolitis, most of the
      patients in the reported literature were males and most of the cases followed a
      benign course. Severe left ventricular dysfunction complicated only two cases of
      C. jejuni myocarditis. We report here a young male with Campylobacter
      myopericarditis. We believe that this is the first reported case of Campylobacter
      associated myopericarditis in The Netherlands. The mechanism by which
      Campylobacter causes myo(peri)carditis remains uncertain, it may be caused by
      direct bacterial invasion of cardiac tissue, bacterial toxins, circulating immune
      complexes, or cytotoxic T-cells. Since the number of C. jejuni infection is
      increasing worldwide, cardiac complications, although rare, are a remarkable
      manifestation of this pathogen and should be always kept in mind.

PMID- 19168239
TI  - Multivessel coronary-ventricular fistulae and ischaemia on cardiac MRI.
AB  - Multivessel coronary ventricular fistulae is a rare coronary anomaly whose origin
      is believed to be from an arterioluminal or arteriosinusoidal connection with the
      ventricle. The clinical and haemodynamic significance of these fistulae have been
      a source of controversy despite varying methods of evaluation. A 69 year old
      female with exertional dyspnoea, atypical chest pain and multivessel coronary to
      left ventricular fistulae underwent cardiac MRI with adenosine stress.
      Subendocardial ischaemia was present in multiple coronary territories therefore
      confirming a coronary steal phenomenon.

PMID- 19168240
TI  - Borrelia-like organism in heart capillaries of patient with Lyme-disease seen by
      electron microscopy.
AB  - A case of a patient who developed an acute myocarditis due to Lyme disease is
      reported. An increased serum antibody titer to Borrelia burgdorferi suggested a
      diagnosis and in addition of basic clinical methods, endomyocardial biopsy
      performed and analyzed by transmission electron microscopy. The lumen of
      myocardial capillaries was founded mostly filled with detritus and fibrin
      precipitate, between them several bacterial fragments were identified. The
      electron-microscopic characteristics of the microorganisms in this specimen,
      revealing irregularly coiled appearance and consistent thickness of 0.2 MUm,
      correspond to the spiral-like structure of Lyme disease borrelia. The presence of
      fibrin deposits on the capillary endothelium and necrosis of myocardiocytes,
      suggests that the cardiopathy in our patient was represent borrelia-mediated
      damage of the heart microcirculation.

PMID- 19168241
TI  - Statin therapy in women: concerns and caution.

PMID- 19168242
TI  - Galen on "syncope".
AB  - This paper studies the Galenic views on syncope. According to Galen, syncope is a
      sudden prostration of the vital powers, without suspension of the respiration and
      it is usually a sign or complication of fever. He believed that "cardiac syncope"
      was a primary illness of the mouth of the oesophagus or of the stomach that
      affected the heart "by sympathy", meaning secondarily. The aetiology, the
      clinical manifestations and the treatment are presented, along with a special
      section referring to the connection between "marasmus", which was supposed to be
      a wasting of the organism of the elders due to "dryness", and syncope. Numerous
      authors before and after Galen treated the subject of the famous "cardiac
      affection": Hippocrates (4th-5th century BC), Asclepiades (2nd-1st century BC),
      Celsus (1st century AD), Aretaeus (2nd century AD), Soranus of Ephesus (2nd
      century AD), and Caelius Aurelianus (5th century AD) all see cardiac syncope as a
      distinct disease. Based on the Galenic descriptions, several modern medical
      conditions may be identified, such as congestive heart failure, hypertrophic
      cardiomyopathy, arrhythmogenic right ventricular dysplasia, congenital long QT
      syndrome or anomalies of the coronary arteries.

PMID- 19168243
TI  - Acute infusion of recombinant human thyrotropin in Langendorff-rat hearts: role
      of a thyrotropin receptor.

PMID- 19168244
TI  - Congenitally corrected transposition of the great arteries in a 59-year-old man:
      ECG-gated 64-slice MDCT findings.

PMID- 19168245
TI  - Usefulness of cardiac resynchronisation therapy in patients with right bundle
      branch block: is viability an important piece of the puzzle?
AB  - BACKGROUND: Benefits of cardiac resynchronisation therapy (CRT) in patients with
      heart failure (HF) and left bundle branch block (LBBB) have been well
      established. The presence of asynchronism and viability predicts response to CRT
      with good accuracy. Viability in the region of the pacing lead as predictor of
      response to CRT in patients with HF, intraventricular asynchrony and right bundle
      branch block (RBBB) has never been evaluated. METHODS: We studied 4 consecutive
      patients with RBBB (QRS>120 ms) advanced ischemic HF, low ejection fraction
      (<=35%) and intraventricular asynchrony >=50 ms scheduled for CRT. Dobutamine
      stress echocardiography (DSE) was performed within the week before CRT. Viability
      was defined as increased wall thickening during DSE. Viability in the region of
      left ventricular (LV) pacing lead was defined as the presence of viability in 2
      contiguous segments. Response was defined by LV reverse remodeling (i.e. >=15%
      reduction in LV end-systolic volume) 3-6 months after CRT. RESULTS: Three
      patients demonstrated LV reverse remodeling at follow-up. Responders showed LV
      end-systolic volume decrease of -31 +/- 16% from baseline to follow-up whereas no
      change was observed in the non responder patient. Similar LV asynchronism was
      found in all patients. All responders had viability in >=2 segments in the region
      of LV pacing. CONCLUSION: This preliminary report suggests that similar reverse
      remodeling can be observed in RBBB patients as patients with LBBB after CRT.
      Intraventricular asynchrony and RBBB, viability in the region of pacing lead may
      help to predict response to CRT in patients with HF.

PMID- 19168246
TI  - Capsaicin and arterial hypertensive crisis.
AB  - Chili peppers are rich in capsaicin. The potent vasodilator calcitonin gene
      related peptide (CGRP) is stored in a population of C-fiber afferents that are
      sensitive to capsaicin. CGRP and peptides released from cardiac C fibers have a
      beneficial effect in myocardial ischemia and reperfusion. It has been reported
      that capsaicin pretreatment can deplete cardiac C-fiber peptide stores.
      Furthermore, it has also been reported that capsaicin-treated pigs have
      significantly increased mean arterial blood pressure compared with controls, and
      that the decrease in CGRP synthesis and release contributes to the elevated blood
      pressure. A case has also been reported of an arterial hypertensive crisis in a
      patient with a large ingestion of peppers and chili peppers the day before. We
      present a case of an arterial hypertensive crisis in a 19-year-old Italian man
      with an abundant ingestion of peppers and of chili peppers the preceding day.
      This case describes an unusual pattern of arterial hypertensive crisis due to
      capsaicin.

PMID- 19168247
TI  - Oxidative stress changes after stent implantation: a randomized comparative study
      of sirolimus-eluting and bare metal stents.
AB  - BACKGROUND: Although oxidative stress plays an important role in the
      pathophysiology of restenosis, its role following the implantation of sirolimus
      eluting stents (SES) is unknown. METHODS: We examined the relation between total
      peroxides (TP), a marker of oxidative stress, and in-stent late luminal loss over
      a 6-month follow-up in patients with stable coronary artery disease and compared
      the results from SES with those from bare metal stents (BMS). We enrolled 75
      consecutive patients, who underwent successful PCI and were randomly allocated to
      SES (n=37) or BMS (n=38). Blood samples were taken 24 h before, at 24 h, 48 h and
      1 month after angioplasty; levels of TP were determined on each occasion. Follow
      up coronary angiography was performed 6-8 months later. RESULTS: TP levels in the
      BMS group were significantly higher at 24 h and 48 h compared to baseline
      (p=0.006 for both). At one month there was a significant decline from the 48 h
      levels (p=0.029) to levels slightly, but not significantly higher than baseline.
      In contrast, in SES TP levels showed no significant changes during the first 48
      h, while they declined to levels somewhat lower than baseline at 30 days. A
      significant correlation was found between TP changes and in-stent late luminal
      loss at 6 months in both groups. CONCLUSION: Our study showed that patients with
      stable coronary artery disease who received SES have a different behavior of
      oxidative stress after stenting compared with BMS, and this could contribute to
      the difference in restenosis rate between these 2 types of stents.

PMID- 19168248
TI  - Is pre-therapeutical FDG-PET/CT capable to detect high risk tumor subvolumes
      responsible for local failure in non-small cell lung cancer?
AB  - BACKGROUND AND PURPOSE: Local failure is a significant issue following
      radiotherapy (RT) for patients with non-small cell lung cancer (NSCLC). The aim
      of this study was to find out whether FDG-PET/CT is capable to predict tumor
      relapse location in patients with NSCLC, in particular to determine high risk
      tumors' subvolumes responsible for local failure. MATERIAL AND METHODS: Ten
      patients with locoregional relapse of NSCLC underwent FDG-PET/CT before, during,
      and in the 4-12 months following curative chemoradiotherapy (ChRT, 66 Gy) using a
      combined PET/CT scanner. Morphologic and metabolic tumor volumetry and an
      evaluation of FDG-uptake dynamics were performed. RESULTS: CT showed partial
      reduction of tumor volume after RT in all patients. PET-revealed partial in eight
      patients and complete metabolic response in two patients during RT. Six to nine
      months after RT, local failure was diagnosed in all patients with both methods.
      Tumor recurrences were localized mostly in the most active ones of pre
      therapeutically metabolic regions of the primary tumor. CONCLUSIONS: Local
      failure in NSCLC appears most common at the primary site and within the
      irradiated target volume with the highest FDG uptake. This observation may be
      useful for further optimization of radiotherapy of NSCLC, for example, by the
      application of additional radiation dose to subvolumes of primary tumors with
      higher FDG uptake.

PMID- 19168249
TI  - Effect of alpha-linolenic, capric and lauric acid on the fatty acid biosynthesis
      in Staphylococcus aureus.
AB  - The antimicrobial activity of alpha-linolenic, capric and lauric acids on
      Staphylococcus aureus was studied in relation to their effect on the de novo
      fatty acid biosynthesis. Labelled acetate was used as integrated carbon source
      and traced in the de novo fatty acid by using a GC-Mass spectrometer and the
      single ion monitoring (SIM) technique. The detection of the incorporation of the
      labelled carbon into the individual cell fatty acids (FAs) provided an insight
      into the different effects of alpha-linolenic, capric and lauric acids on the FA
      biosynthesis. The results suggested that FAs pathway is the major target of alpha
      linolenic acid and that other enzymes in addition to FabI are involved in S.
      aureus response mechanism when medium chain fatty acids are present.

PMID- 19168250
TI  - Risk scoring for setting priorities in a monitoring of antimicrobial resistance
      in meat and meat products.
AB  - Meat and meat products can be contaminated with different species of bacteria
      resistant to various antimicrobials. The human health risk of a type of meat or
      meat product carry by emerging antimicrobial resistance depends on (i) the
      prevalence of contamination with resistant bacteria, (ii) the human health
      consequences of an infection with a specific bacterium resistant to a specific
      antimicrobial and (iii) the consumption volume of a specific product. The
      objective of this study was to compare the risk for consumers arising from their
      exposure to antibiotic resistant bacteria from meat of four different types
      (chicken, pork, beef and veal), distributed in four different product categories
      (fresh meat, frozen meat, dried raw meat products and heat-treated meat
      products). A semi-quantitative risk assessment model, evaluating each food chain
      step, was built in order to get an estimated score for the prevalence of
      Campylobacter spp., Enterococcus spp. and Escherichia coli in each product
      category. To assess human health impact, nine combinations of bacterial species
      and antimicrobial agents were considered based on a published risk profile. The
      combination of the prevalence at retail, the human health impact and the amount
      of meat or product consumed, provided the relative proportion of total risk
      attributed to each category of product, resulting in a high, medium or low human
      health risk. According to the results of the model, chicken (mostly fresh and
      frozen meat) contributed 6.7% of the overall risk in the highest category and
      pork (mostly fresh meat and dried raw meat products) contributed 4.0%. The
      contribution of beef and veal was of 0.4% and 0.1% respectively. The results were
      tested and discussed for single parameter changes of the model. This risk
      assessment was a useful tool for targeting antimicrobial resistance monitoring to
      those meat product categories where the expected risk for public health was
      greater.

PMID- 19168251
TI  - Prevalence of non-alcoholic fatty liver disease in urban south Indians in
      relation to different grades of glucose intolerance and metabolic syndrome.
AB  - AIM: To estimate prevalence of non-alcoholic fatty liver disease (NAFLD) and its
      association with glucose intolerance (type 2 diabetes (DM), prediabetes) and
      metabolic syndrome (MS) in urban south Indians. METHODS: This study was carried
      out in 541 subjects (response rate 92%) of the original sample of 26,001 subjects
      in the Chennai Urban Rural Epidemiology Study maintaining the representativeness.
      Anthropometry and lipid estimations were done in all and oral glucose tolerance
      test in all, except self-reported diabetic subjects. NAFLD was diagnosed by
      ultrasonography and MS by modified Adult Treatment Panel III (ATP III) criteria.
      DM, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were
      defined using WHO consulting group criteria. RESULTS: Overall prevalence of NAFLD
      was 32% (173/541 subjects) (men: 35.1%, women: 29.1%, p=0.140). Prevalence of
      most cardio-metabolic risk factors was significantly higher in NAFLD subjects.
      Prevalence of NAFLD (54.5%) was higher in subjects with DM compared to those with
      prediabetes (IGT or IFG) (33%), isolated IGT (32.4%), isolated IFG (27.3%) and
      normal glucose tolerance (NGT) (22.5%) (DM vs. prediabetes: p<0.05, DM vs. NGT:
      p<0.001, prediabetes vs. NGT: p<0.05). Even after adjusting for age, gender and
      waist circumference, NAFLD was associated with diabetes (OR: 2.9, 95% C.I.: 1.9
      4.6, p<0.001) and MS (OR: 2.0, 95% C.I.: 1.3-3.1, p<0.001). CONCLUSION: NAFLD is
      present in a third of urban Asian Indians and its prevalence increases with
      increasing severity of glucose intolerance and in MS. This is the first
      population-based prevalence of NAFLD from south Asia which faces the brunt of the
      diabetes epidemic.

PMID- 19168252
TI  - Microalbuminuria and metabolic risk factors in patients with type 2 diabetes in
      primary care setting in Thailand.
AB  - OBJECTIVE: To determine the prevalence of microalbuminuria and associated risk
      factors in patients with type 2 diabetes in primary care. METHODS: Clinical
      information of diabetic patients in 70 primary care units in Thailand was
      collected in a cross-sectional survey. Multinomial logistic regression model was
      used to examine several clinical risk factors with microalbuminuria and
      macroalbuminuria. RESULTS: A total of 4162 patients were included. The prevalence
      of microalbuminuria was 39.12% and macroalbumninuria was 7.83%. The proportion of
      patients with HbA1c<7% was 37.9%. Independent risk factors for microalbuminuria
      and macroalbuminuria included HbA1c (adjusted OR 1.54, 95%CI 1.30-1.83 and 2.06,
      95%CI 1.49-2.84 per unit increase in HbA1c, respectively), triglyceride
      >/=1.7mmol/L (1.31, 1.11-1.56 and 1.44, 1.06-1.98), hypertension (1.31, 1.10-1.54
      and 1.64, 1.23-2.20), and duration of diabetes >/=5 years (1.31, 1.11-1.55 and
      2.39, 1.74-3.28). Metabolic syndrome was associated with macroalbuminuria (OR
      1.36, 95%CI 1.01-1.84). CONCLUSION: The high prevalence of microabuminuria and
      suboptimal glycemic control for the diabetic patients were found to highlight the
      need to improve in control of glycemia and metabolic risk factors.

PMID- 19168253
TI  - Multi-center intervention study on glycohemoglobin (HbA1c) and serum, high
      sensitivity CRP (hs-CRP) after local anti-infectious periodontal treatment in
      type 2 diabetic patients with periodontal disease.
AB  - The purpose of this study was to examine whether periodontal treatment
      incorporating topical antibiotic therapy affects on levels of glycohemoglobin
      (HbA1c) and serum high-sensitivity C-reactive protein (hs-CRP) in type 2 diabetic
      patients with periodontal disease, and to explore the relationship between CRP
      and glycemic control. The whole intervention group (n=32), which underwent anti
      infectious periodontal treatment, showed only transient reduction in HbA1c levels
      without any change in hs-CRP, while the control group (n=17) did not show any
      changes in HbA1c or hs-CRP. Multiple regression analysis of all subjects revealed
      that BMI and change in hs-CRP correlated significantly with the reduction of
      HbA1c at 6 months after the periodontal treatment. Based on the results of
      multiple regression analysis, the intervention group was subdivided into two
      groups: those in which hs-CRP levels decreased (CRP-D group), and those in which
      hs-CRP levels unchanged or increased (CRP-N group) (n=16, respectively), and re
      analysis was conducted based upon these subgroups. In the CRP-D subgroup, HbA1c
      was significantly reduced at the end of the study, but it did not decrease in the
      CRP-N subgroup. The decrease of HbA1c in the CRP-D subgroup following periodontal
      treatment was significantly greater than that in the CRP-N subgroup. BMI of each
      group remained unchanged in this study at the end of the study. Thus, the results
      suggested that periodontal treatment with topical antibiotics improves HbA1c
      through reduction of CRP, which may relate to amelioration of insulin resistance,
      in type 2 diabetic patients with periodontal disease.

PMID- 19168254
TI  - Mouse mammary tumour virus-like virus (MMTV-LV) is present within the liver in a
      wide range of hepatic disorders and unrelated to nuclear p53 expression or
      hepatocarcinogenesis.
AB  - BACKGROUND/AIMS: The human equivalent of mouse mammary tumour virus (MMTV-LV) may
      have a role in the pathogenesis of primary biliary cirrhosis (PBC) and breast
      carcinogenesis. We investigated MMTV-LV prevalence in patients with liver disease
      of diverse aetiology and associations with hepatic expression of hormonal
      receptors, p53 protein and complicating hepatocarcinogenesis. METHODS: Nested PCR
      for MMTV-LV envelope was performed using tissue from 210 patients with liver
      disease and 20 patients with histologically normal liver. Hepatic expression of
      estrogen receptor-alpha (ER-alpha), progesterone receptor (PgR) and p53 protein
      was determined by immunohistochemistry. MMTV-LV expression was also determined in
      hepatocellular carcinoma (HCC) tissue from 21 patients, in 11 of whom paired non
      tumourous liver tissue was available for comparison. RESULTS: MMTV-LV envelope
      sequences were present in 25% (53/210) of liver disease biopsies but not in
      histologically normal liver (0/20) (P=0.02). There was no association between
      MMTV-LV presence and hepatic expression of ER-alpha or p53 protein. No liver
      sections were PgR positive. MMTV-LV prevalence was not significantly different in
      HCC tissue, paired non-tumourous chronic liver disease tissue from the same
      patients and liver disease tissue from patients without complicating HCC.
      CONCLUSIONS: Hepatic expression of MMTV-LV is evident in a wide range of non
      cirrhotic and cirrhotic liver diseases, irrespective of ER-alpha, PgR or p53
      status, and unrelated to complicating HCC.

PMID- 19168255
TI  - Searching for cost effectiveness thresholds in the NHS.
AB  - OBJECTIVES: The UK's National Institute of Health and Clinical Excellence (NICE)
      has an explicit cost-effectiveness threshold for deciding whether or not services
      are to be provided in the National Health Service (NHS), but there is currently
      little evidence to support the level at which it is set. This study examines
      whether it is possible to obtain such evidence by examining decision making
      elsewhere in the NHS. Its objectives are to set out a conceptual model linking
      NICE decision making based on explicit thresholds with the thresholds implicit in
      local decision making and to gauge the feasibility of (a) identifying those
      implicit local cost effectiveness thresholds and (b) using these to gauge the
      appropriateness of NICE's explicit threshold. METHODS: Structured interviews with
      senior staff, together with financial and public health information, from six NHS
      purchasers and 18 providers. A list of health care services introduced or
      discontinued in 2006/7 was constructed. Those that were in principle amenable to
      estimation of a cost-effectiveness ratio were examined. RESULTS: It was feasible
      to identify decisions and to estimate the cost-effectiveness of some. These were
      not necessarily 'marginal' services. Issues include: services that are dominated
      (or dominate); decisions about how, rather than what, services should be
      delivered; the lack of local cost effectiveness evidence; and considerations
      other than cost-effectiveness. CONCLUSIONS: A definitive finding about the
      consistency or otherwise of NICE and NHS cost effectiveness thresholds would
      require very many decisions to be observed, combined with a detailed
      understanding of the local decision making processes.

PMID- 19168256
TI  - Preferences of older patients and choice of treatment location in the UK: a
      binary choice experiment.
AB  - Current National Health Service (NHS) policy places importance on allowing
      patients to choose the time and location of their treatment. However, existing
      evidence suggests that older people have distinct needs and preferences from
      those of the general population. This study aimed to elicit preferences over
      cataract surgery from older people using a stated preference experiment. In order
      to reduce the cognitive load of the experiment, a binary choice format (accept
      treatment, reject treatment) was used. Analysis suggests that the strongest
      determinant of whether or not to accept treatment may be whether or not a
      consultant performs the operation. In monetary equivalents, a one mile increase
      in travel and a 1 week increase in waiting time are both valued at approximately
      2 pounds, whilst consultant-led care is valued at approximately 25 pounds. Whilst
      the majority of our sample ultimately selected the closest treatment location
      available the results here suggest that older people are able to make trade-offs
      between pertinent attributes of choice. Here, the closest treatment location may
      simply be the one that best reflects their preferences.

PMID- 19168257
TI  - Estimating the size of the bacterial pan-genome.
AB  - The 'pan-genome' denotes the set of all genes present in the genomes of a group
      of organisms. Here, we extend the pan-genome concept to higher taxonomic units.
      Using 573 sequenced genomes, we estimate the size of the bacterial pan-genome
      based on the frequency of occurrences of genes among sampled genomes. Using gene-
      and genome-centered approaches, we characterize three distinct pools of gene
      families that comprise the bacterial pan-genome, each evolving under different
      evolutionary constraints. Our findings indicate that the pan-genome of the
      bacterial domain is of infinite size (the Bacteria as a whole have an open pan
      genome) and that approximately 250 genes per genome belong to the extended
      bacterial core genome.

PMID- 19168258
TI  - The detection of peripheral lung cancer by MAGE A1-6 RT-nested PCR in bronchial
      washing specimens.
AB  - BACKGROUND: With expansion of lung cancer screening by computed tomography (CT)
      and increased incidence of adenocarcinoma, we encountered more peripheral nodules
      to be identified. We evaluated detection rates of the melanoma antigen genes
      (MAGE) RT-nested PCR using a common MAGE A1-6 primer in bronchoscopic washing
      samples from patients with bronchoscopically invisible peripheral nodules, and
      compared with those of conventional cytology and percutaneous needle aspiration
      biopsy (PCNB). MATERIALS AND METHODS: Forty-two patients with bronchoscopically
      invisible peripheral lung nodules were studied. Bronchoscopic washing specimens
      were collected by instilling 20ml of normal saline into a tumor bearing segment
      and retrieving samples. Samples were split and analyzed by MAGE RT-PCR and
      conventional cytology. A PCNB was performed in all but two patients. Twenty-eight
      lesions were diagnosed as lung cancers and 14 as benign lung diseases. We
      evaluated MAGE A1-6 RT-nested PCR, cytology, and PCNB results and analyzed them
      according to histologic cell types and tumor sizes. RESULTS: In bronchial washing
      samples, the detection rates of MAGE A1-6 RT-nested PCR (67.9%) were higher than
      that of conventional cytology (21.4%, p=.04) and similar to that of PCNB (73.1%,
      p=.45) in 28 cancer patients. In terms of histologic types, the detection rates
      of MAGE A1-6 RT-nested PCR, conventional cytology, and PCNB were 78.6%, 21.4% and
      64.3% in adenocarcinoma, 70%, 20% and 77.8% in squamous cell carcinoma,
      respectively. The sensitivity of conventional cytology was significantly lower
      than that of MAGE RT-nested PCR or PCNB regardless of tumor histology p=.04,
      p=.025, respectively, in adenocarcinoma; p=.035, p=.04, respectively, in squamous
      cell carcinoma). In terms of tumor size, the corresponding detection rates were
      73.3%, 6.7% and 73.3% for tumors smaller than 3cm (N=15), and 61.5%, 38.5% and
      72.7% for tumors larger than 3cm (N=13). CONCLUSIONS: MAGE A1-6 RT-nested PCR
      showed higher detection rates in the bronchial washes of peripheral lung cancer
      patients than conventional cytology testing. This method is simple and robust,
      and it could be effectively utilized as a peripheral lung cancer detection tool
      in clinical laboratories.

PMID- 19168259
TI  - Core classification of lung cancer: correlating nuclear size and mitoses with
      ploidy and clinicopathological parameters.
AB  - We attempted to establish a microscopy based tumour characterization providing
      insight into the genetics of cancer cells and in particular their DNA ploidy. The
      core classification defined semi-quantitative criteria for scoring the nuclear
      size ranging from small (core score 1) to giant nuclei (core score 4). By listing
      all nuclear sizes according to their relative frequencies it provided a measure
      for core size variability as a correlate of nuclear pleomorphism. Additionally,
      the mitosis size, their variability and the presence/abundance of tripolar and
      tetrapolar mitoses were determined. This classification was applied to 155 lung
      cancer samples from all major histologic types and the results were correlated
      with the analysis by DNA image cytometry and patient survival. The morphological
      assessments correlated highly significantly with the DNA ploidy parameters, e.g.
      small cell lung carcinomas showed the smallest values for nuclear size (mean core
      score of 1.18) and DNA content (DNA index mean of 2.08c) being highly
      significantly different from adenocarcinomas (1.95/3.10c), large cell lung
      carcinoma (2.00/3.26c) and squamous cell carcinoma (2.20/3.42c). In non-small
      cell lung carcinoma (NSCLC) in general and adenocarcinoma in particular, the core
      size variability correlated significantly with grading and survival. Furthermore,
      parameters indicative for chromosomal variability, i.e. 2c deviation index and 5c
      exceeding rate, were predictors of poor survival in NSCLC patients. As a
      complement to histologic tumour diagnosis the core classification should help to
      better stratify cancer subtypes.

PMID- 19168260
TI  - Fractionated stereotactic body radiation therapy for medically inoperable stage I
      lung cancer adjacent to central large bronchus.
AB  - PURPOSE: To assess the body-framed stereotactic body radiation therapy (SBRT)
      results and toxicity for medically inoperable stage I lung cancer adjacent to
      central large bronchus and then compare the results with those of SBRT in
      peripheral lung tumor in the aspects of survival and SBRT-related pulmonary
      toxicities. MATERIALS: From June 1999 to May 2006, 32 patients diagnosed as stage
      I, T1N0 or T2N0, resectable NSCLC were treated with body-frame based fractionated
      SBRT. Thirty-one patients had several medical problems conflicting surgical
      procedure. Stereotactic body frame was used for improving setup accuracy. Doses
      of 10-20 Gy per fraction were delivered to the planning target volume (PTV) up to
      a total dose of 40-60 Gy with three to four fractions on consecutive days.
      Centrally located tumor was defined as the tumor within 2 cm apart from large
      bronchial tree, and was subdivided into bronchial (main/lobar bronchus) and
      peribronchial (segmental or distal). RESULTS: Median follow-up was 26.5 months.
      The 6-month major response rate, including complete or partial response, was
      53.1%. One patient showed progressive disease 1 month after SBRT. The 1- and 2
      year actuarial local tumor control rates were both 85.3%. Overall survival was
      70.9% at 1 year and 38.5% at 2 years, and survival was not correlated with SBRT
      dose. Of 9 patients with centrally located tumors, three (33%) experienced Grades
      3-5 pulmonary toxicities. Eight patients showed partial or complete bronchial
      stricture and secondary loss of normal lung volume. Median time to bronchial
      stricture was 20.5 months. Overall survival did not differ by tumor location.
      CONCLUSIONS: SBRT in this fractionation should not be given to central lung
      tumors because it can cause the late major airway toxicities in some patients.
      More protracted hypofractionated treatment regimen may be more safe than that
      used usually in SBRT for central lung tumors.

PMID- 19168261
TI  - Review of mobile communication devices as potential reservoirs of nosocomial
      pathogens.
AB  - Innovation in mobile communication technology has provided novel approaches to
      the delivery of healthcare and improvements in the speed and quality of routine
      medical communication. Bacterial contamination of mobile communication devices
      (MCDs) could be an important issue affecting the implementation of effective
      infection control measures and might have an impact on efforts to reduce cross
      contamination. This review examines recent studies reporting bacterial
      contamination of MCDs, most demonstrating that 9-25% of MCDs are contaminated
      with pathogenic bacteria. We examine previously investigated risk factors for MCD
      contamination in addition to work on surface decontamination of the device.
      Recommendations to reduce contamination risks include staff education, strict
      hand hygiene measures, guidelines on device cleaning and consideration of the
      restrictions regarding use of mobile phone technology in certain high risk areas,
      for example, operating theatres, intensive care units and burns units. Further
      work is required to evaluate the benefit of such interventions on MCD
      contamination and to determine whether a link exists between contamination and
      subsequent patient infection.

PMID- 19168262
TI  - Synthesis and antimicrobial studies of novel methylene bridged benzisoxazolyl
      imidazo[2,1-b][1,3,4]thiadiazole derivatives.
AB  - Novel methylene bridged benzisoxazolyl imidazo[2,1-b][1,3,4]thiadiazoles (3a-f)
      were synthesized from benzisoxazolyl-3-acetic acid and thiosemicarbazide.
      Reaction of 3 with bromine in glacial acetic acid in the presence of anhydrous
      sodium acetate yielded the corresponding 5-bromo derivatives (4a-f). While
      compound 3 furnished the 5-nitroso derivatives (5a-f) on refluxing with sodium
      nitrite solution. Thiocyanato derivatives (6a-f) were obtained by treating the
      imidazothiadiazole 3 with bromine and potassium thiocyanate in glacial acetic
      acid at room temperature. The structures of the newly synthesized compounds were
      confirmed by IR, NMR, mass and elemental analysis. All the compounds were
      screened for their antibacterial and antifungal activities. Some of the compounds
      displayed very good antibacterial and antifungal activity.

PMID- 19168263
TI  - Synthesis, pharmacological and in silico evaluation of 1-(4-di-hydroxy-3,5-dioxa
      4-borabicyclo[4.4.0]deca-7,9,11-trien-9-yl)-2-(tert-butylamino)ethanol, a
      compound designed to act as a beta2 adrenoceptor agonist.
AB  - In this study, 1-(4-di-hydroxy-3,5-dioxa-4-borabicyclo[4.4.0]deca-7,9,11-trien-9
      yl)-2-(tert-butylamino)ethanol, (BR-AEA), was designed, synthesized,
      characterized and tested in docking studies and in vitro. Previous to its
      synthesis, a set of compounds, including well-known ligands and boron containing
      compounds, were studied under docking simulations. BR-AEA showed greater affinity
      than these well-known agonists and was found to be slightly closer than
      salbutamol to the residues in the TM5 and TM3 of the beta(2) adrenoceptor
      (beta(2)AR), making a greater number of interactions with them, including some
      that are apparently key to greater affinity and beta(2)AR activation. This study
      suggests that affinity is closely related to the interactions of the boron atom,
      as well as the capacity of boronic acid moieties to make a network of hydrogen
      bonds with the beta(2)AR. In vitro, the relaxing effects of BR-AEA on isolated
      guinea pig tracheal rings were compared with salbutamol. The EC(50) values for BR
      AEA were at least five-fold lower than for salbutamol, showing the greater
      potency of the former. Additionally, propranolol and ICI 118,551 showed
      competitive antagonism in relation to the relaxing effect of the test compound
      (pA(2) 6.204+/-0.367 and 9.089+/-0.470, respectively).

PMID- 19168264
TI  - Melatonin: Quantum-chemical and biochemical investigation of antioxidant
      activity.
AB  - Experimental and theoretical investigation of the antioxidant activity of
      melatonin is carried out. The theoretical approach comprises the evaluation of
      several appropriate descriptors of scavenging activity with the help of quantum
      chemistry methods. The values obtained are compared with available data for
      substances with established antioxidant properties. One of the most widely used
      markers for in vivo free radical oxidation processes is malondialdehyde (MDA) as
      an end product of membrane lipid peroxidation. Experimental support of the
      computed scavenging parameters is provided by estimation of the effect of
      supplementary melatonin therapy on the plasma levels of MDA in CRF patients on
      maintenance HD therapy. Different reaction paths have been considered and related
      to the obtained data, allowing speculations about the reaction mechanism and the
      antioxidant potential of melatonin for practical purposes.

PMID- 19168265
TI  - Improved performance of a biomaterial-based cation exchanger for the adsorption
      of uranium(VI) from water and nuclear industry wastewater.
AB  - The amine-modified polyhydroxyethylmethacrylate (poly(HEMA))-grafted biomaterial
      (tamarind fruit shell, TFS) carrying carboxyl functional groups at the chain end
      (PGTFS-COOH) was prepared and used as an adsorbent for the removal of uranium(VI)
      from water and nuclear industry wastewater. FTIR spectral analysis revealed that
      U(VI) ions and PGTFS-COOH formed a chelate complex. The adsorption process was
      relatively fast, requiring only 120 min to attain equilibrium. The adsorption
      kinetic data were best described by the pseudo-second-order equation. The
      equilibrium adsorption data were correlated with the Sips isotherm model. The
      maximum U(VI) ions uptake with PGTFS-COOH was estimated to be 100.79 mg/g. The
      complete removal of 10mg/L U(VI) from simulated nuclear industry wastewater was
      achieved by 3.5 g/L PGTFS-COOH. The reusability of the adsorbent was demonstrated
      over 4 cycles using NaCl (1.0M)+HCl (0.5M) solution mixture to de-extract the
      U(VI). The results show that the PGTFS-COOH tested is very promising for the
      recovery of U(VI) from water and wastewater.

PMID- 19168266
TI  - Speciation of radionuclides in the environment.

PMID- 19168267
TI  - Augmentation with silicone stabilizes proximal femur fractures: an in vitro
      biomechanical study.
AB  - BACKGROUND: Prevention of hip fracture surgery in the elderly imposes great
      benefit for patient care as well as for society. The incidence of contra-lateral,
      second hip fractures after hip fracture surgery is as high as 20%. Augmentation
      of the contra-lateral proximal femur with silicone femoroplasty during hip
      fracture surgery of the ipsilateral hip could be a new preventive strategy. This
      study compared the degree of dislocation after a controlled induced fracture
      between treated and control cadaver femora. METHODS: Ten paired cadaver femora
      were randomly assigned for silicone femoroplasty and biomechanically tested for
      fracture load and dislocation against their native contra-lateral control. A load
      testing machine was used for fracture induction. All femurs were first fractured
      in a simulated fall configuration followed by dislocation in a "single leg
      stance" configuration. Dislocation was accessed using the AO-classification and
      measuring the Caput-Collum-Diaphysis angle. FINDINGS: Fracture loads were
      approximately 10% lower in the treated group (P=0.304). Forces needed to
      dislocate the proximal femur fractures did not significantly differ in both
      groups nor did the fracture type and AO-classification. All treated femurs showed
      complete reposition according to Caput-Collum-Diaphysis angle after dislocation
      versus only two of the controls (P<0.001). INTERPRETATION: From the results of
      this study we conclude silicone femoroplasty stabilizes the proximal femur by
      restoring hip geometry according to the Caput-Collum-Diaphysis angle after
      fracture. Future improvements in minimal invasive excavation and injection could
      make silicone femoroplasty an attractive alternative strategy in the prevention
      of hip fracture surgery in the growing population of low-demand, elderly
      patients.

PMID- 19168268
TI  - Phenanthrene uptake by Medicago sativa L. under the influence of an arbuscular
      mycorrhizal fungus.
AB  - Phenanthrene uptake by Medicago sativa L. was investigated under the influence of
      an arbuscular mycorrhizal fungus. Inoculation of lucerne with the arbuscular
      mycorrhizal fungus Glomus etunicatum L. resulted in higher phenanthrene
      accumulation in the roots and lower accumulation in the shoots compared to non
      mycorrhizal controls. Studies on sorption and desorption of phenanthrene by roots
      and characterization of heterogeneity of mycorrhizal and non-mycorrhizal roots
      using solid-state (13)C nuclear magnetic resonance spectroscopy ((13)C NMR)
      demonstrated that increased aromatic components due to mycorrhizal inoculation
      resulted in enhanced phenanthrene uptake by the roots but lower translocation to
      the shoots. Direct visualization using two-photon excitation microscopy (TPEM)
      revealed higher phenanthrene accumulation in epidermal cells of roots and lower
      transport into the root interior and stem in mycorrhizal plants than in non
      mycorrhizal controls. These results provide some insight into the mechanisms by
      which arbuscular mycorrhizal inoculation may influence the uptake of organic
      contaminants by plants.

PMID- 19168269
TI  - Antibiotic removal from water: elimination of amoxicillin and ampicillin by
      microscale and nanoscale iron particles.
AB  - Zerovalent iron powder (ZVI or Fe(0)) and nanoparticulate ZVI (nZVI or nFe(0))
      are proposed as cost-effective materials for the removal of aqueous antibiotics.
      Results showed complete removal of Amoxicillin (AMX) and Ampicillin (AMP) upon
      contact with Fe(0) and nFe(0). Antibiotics removal was attributed to three
      different mechanisms: (i) a rapid rupture of the beta-lactam ring (reduction),
      (ii) an adsorption of AMX and AMP onto iron corrosion products and (iii)
      sequestration of AMX and AMP in the matrix of precipitating iron hydroxides (co
      precipitation with iron corrosion products). Kinetic studies demonstrated that
      AMP and AMX (20 mg L(-1)) undergo first-order decay with half-lives of about
      60.3+/-3.1 and 43.5+/-2.1 min respectively after contact with ZVI under oxic
      conditions. In contrast, reactions under anoxic conditions demonstrated better
      degradation with t(1/2) of about 11.5+/-0.6 and 11.2+/-0.6 min for AMP and AMX
      respectively. NaCl additions accelerated Fe(0) consumption, shortening the
      service life of Fe(0) treatment systems.

PMID- 19168270
TI  - Occurrence, source diagnosis, and biological effect assessment of DDT and its
      metabolites in various environmental compartments of the Pearl River Delta, South
      China: a review.
AB  - This review summarizes and analyzes available data in the literature (mostly
      after 2000) on the occurrence of dichlorodiphenyltrichloroethane (DDT) and its
      main metabolites, dichlorodiphenyldichloroethane (DDD) and
      chlorodiphenyldichloroethylene (DDE), in the environment of the Pearl River Delta
      (PRD), South China. Generally, the concentration levels of the sum of DDT, DDD,
      and DDE, designated as DDTs thereafter, have not significantly declined since
      1983. However, the composition of DDTs residues has changed with time. DDTs in
      soil, freshwater sediment and freshwater fish species were mainly residues from
      chronological use. There is evidence that new point sources, such as dicofol and
      anti-fouling paint, may have contributed DDTs to various environmental
      compartments. Risk assessment against existing criteria indicated that the levels
      of DDTs in water and some fish species may pose adverse effects to humans or
      wildlife, and those in sediment/soil may also cause negative impacts to the eco
      environment of the PRD.

PMID- 19168272
TI  - The role of low-spatial frequencies in lexical decision and masked priming.
AB  - Spatial frequency filtering was used to test the hypotheses that low-spatial
      frequency information in printed text can: (1) lead to a rapid lexical decision
      or (2) facilitate word recognition. Adult proficient readers made lexical
      decisions in unprimed and masked repetition priming experiments with unfiltered,
      low-pass, high-pass and notch filtered letter strings. In the unprimed
      experiments, a filtered target was presented for 105 or 400 ms followed by a
      pattern mask. Sensitivity (d') was lowest for the low-pass filtered targets at
      both durations with a bias towards a 'non-word' response. Sensitivity was higher
      in the high-pass and notch filter conditions. In the priming experiments, a
      forward mask was followed by a filtered prime then an unfiltered target. Primed
      words, but not non-words, were identified faster than unprimed words in both the
      low-pass and high-pass filtered conditions. These results do not support a unique
      role for low-spatial frequency information in either facilitating or making rapid
      lexical decisions.

PMID- 19168271
TI  - Occupation and plasma fibrinogen in Japanese male and female workers: the Jichi
      Medical School Cohort study.
AB  - This study explored the association between socioeconomic indices and plasma
      fibrinogen levels in Japanese male and female workers. Occupational category
      (white-collar vs. blue-collar) and position (manager vs. non-manager) were
      examined as relevant socioeconomic indices. The study population was a total of
      1677 male and 1747 female workers aged 65 and younger taken from the Jichi
      Medical School Cohort study, a multicenter study designed to explore
      cardiovascular risk factors in the Japanese population. The association between
      socioeconomic indices and plasma fibrinogen levels was examined after taking into
      account several variables such as age, educational attainment, job strain,
      alcohol consumption, and smoking status and (for women) menopause status. Male
      white-collar workers had significantly lower fibrinogen levels than blue-collar
      workers. However, no significant association was found between occupational
      position and plasma fibrinogen for men. Occupational category interacted with
      occupational position for women. Among white-collar women, those in non
      managerial positions showed higher levels of fibrinogen than those in managerial
      positions; among blue-collar women, there was no such difference. The association
      of occupational category and position on fibrinogen levels varied as a function
      of gender, implying that gender-specific socioeconomic differences could exist in
      cardiovascular risks in Japanese workers.

PMID- 19168273
TI  - Mineral distribution and CLSM analysis of secondary caries inhibition by
      fluoride/MDPB-containing adhesive system after cariogenic challenges.
AB  - OBJECTIVE: To evaluate the inhibition zone formation (IZ) and mineral
      distribution along the interface of adhesive systems either containing fluoride
      and antibacterial primer or not, after chemical and biological artificial caries
      challenges. METHODS: Forty-eight third molars were used. Artificial caries was
      developed with S. mutans in a 4mm x 4mm area of occlusal dentin surface. Carious
      dentin was removed and cavities were restored with Adper Scotchbond Multi-Purpose
      (SBM) and Clearfil Protect Bond (CPB) (n=24). Samples were submitted to secondary
      caries development by chemical (C) (acidic gel) or biological (B) (S. mutans
      culture) methods for 5 days. Four groups were tested (n=12): (1) SC (SBM+C); (2)
      SB (SBM+B); (3) CC (CPB+C); (4) CB (CPB+B). The IZ and outer lesion (OL)
      formations were analyzed by confocal laser scanning microscopy (CLSM). The
      distribution of calcium (Ca) and phosphorus (P) content along the interface was
      analyzed by micro X-ray fluorescence spectrometer by energy-dispersive
      (microEDX). RESULTS: The frequency of IZ formation and mean values of IZ
      thickness differed among the groups. The CC group presented the lowest OL depth.
      microEDX analysis showed that CPB had the highest mineral loss by the biological
      method, but the lowest mineral loss by the chemical method. SC and SB groups
      showed intermediate values of mineral loss. CONCLUSION: The mineral loss along
      the dentin/restoration interface was affected by the artificial caries method,
      and hybrid layer formation by adhesive systems used. The adhesive system
      containing fluoride and antibacterial primer did not prevent secondary caries
      formation.

PMID- 19168274
TI  - Antepartum uterine rupture in previous caesarean sections presenting as advanced
      extrauterine pregnancies: lessons learnt.
AB  - In present day obstetric practice, rupture of a previously scarred uterus should
      be uncommon. It occurs in <1% of previous caesarean sections and most cases occur
      during labour and have evidence of abnormal fetal heart rate patterns, vaginal
      bleeding and continuous abdominal pains. Clinicians are alert to these symptoms
      and signs, and therefore immediate action is taken to prevent further maternal
      morbidity and mortality. However, rupture of a previously scarred uterus may
      occur occasionally in the antepartum period. In such circumstances, the patients
      may be haemodynamically stable and present with loss of fetal movements and vague
      abdominal pains, and are treated expectantly for a period of time because an
      initial diagnosis of advanced extra-uterine pregnancy is made. We present a
      series of 7 cases, all of whom had one or more previous caesarean sections, were
      haemodynamically stable and were being managed expectantly, to illustrate the
      fact that ruptured uterus should be strongly considered in the differential
      diagnosis, even when the clinical signs and sonography are suggestive of an
      advanced extra-uterine pregnancy. The lessons in these cases fall into the
      following categories: 1. Ruptured uteri can occur in non-labouring women with
      previous lower segment caesarean sections. 2. Absence of signs of peritonism is
      possibly due to the fact that the pregnancy is extruded through the uterine
      rupture with the amniotic sac being intact and there is little or no bleeding
      into the abdominal cavity or vaginally. 3. Imaging techniques should focus on the
      size of the uterus, as an enlarged uterus in the background of an advanced extra
      uterine pregnancy in a previously scarred uterus is highly suggestive of uterine
      rupture. Clinicians must strongly consider ruptured uteri in non labouring women
      with previous caesarean sections even when imaging modalities suggest an advanced
      extrauterine pregnancy. This will lead to earlier surgical treatment and
      appropriate information being provided to patients.

PMID- 19168276
TI  - Complications of laparoscopic surgery for renal masses: prevention, management,
      and comparison with the open experience.
AB  - CONTEXT: The initial excitement about the laparoscopic treatment of renal masses
      has been tempered by concerns related to increased operative time, technical
      complexity, and the suitability of laparoscopic approaches to oncologic surgery.
      OBJECTIVE: To provide a comprehensive review of intraoperative and postoperative
      complications and their prevention and management during laparoscopic surgery of
      renal tumors. EVIDENCE ACQUISITION: A literature review of the Medline and Google
      Scholar databases was performed, searching for renal cell carcinoma, renal mass,
      laparoscopy, laparoscopic radical nephrectomy, open radical nephrectomy,
      laparoscopic partial nephrectomy, open partial nephrectomy, laparoscopic
      cryoablation, laparoscopic radiofrequency ablation, complications, intra
      operative, and post-operative. English-language articles published between 1990
      and 2008 were reviewed. EVIDENCE SYNTHESIS: Laparoscopic radical nephrectomy
      (LRN), whether transperitoneal or retroperitoneal, can be performed safely. The
      overall complication rate is low and does not significantly differ from that of
      the open experience. Laparoscopic partial nephrectomy (LPN), in contrast, is a
      technically challenging procedure. Although the intermediate oncologic outcomes
      are comparable to those of the open experience, there are concerns related to
      warm ischemia time, and there is a risk of major complications such as urinary
      leakage and hemorrhage requiring transfusion. Laparoscopic-assisted ablative
      therapies (cryotherapy and radiofrequency) are being performed more commonly for
      the treatment of small exophytic renal lesions with a low complication rate and
      intermediate oncologic outcomes similar to LRN and LPN. CONCLUSIONS:
      Complications associated with the laparoscopic management of renal masses vary
      among the different procedures and with surgeon experience. The rate of
      complication appears to be similar to that of open surgery.

PMID- 19168275
TI  - Investigation of intermolecular hydrogen bond interactions in crystalline L
      cysteine by DFT calculations of the oxygen-17, nitrogen-14, and hydrogen-2 EFG
      tensors and AIM analysis.
AB  - A systematic computational study is carried out to investigate hydrogen bond (HB)
      interactions in the real crystalline structures of L-cysteine at 30 and 298 K by
      density functional theory (DFT) calculations of electric field gradient (EFG)
      tensors at the sites of O-17, N-14, and H-2 nuclei. One-molecule (monomer) and
      nine-molecule (cluster) models of L-cysteine are created by available crystal
      coordinates at both temperatures and the EFG tensors are calculated for both
      models to indicate the effect of HB interactions on the tensors. The calculated
      EFG tensors at the level of B3LYP and B3PW91 DFT methods and 6-311++G** and cc
      pVTZ basis sets are converted to those experimentally measurable nuclear
      quadrupole resonance (NQR) parameters i.e. quadrupole coupling constants (qcc)
      and asymmetry parameters (eta(Q)). The evaluated NQR parameters reveal that the
      EFG tensors of (17)O, (14)N, and (2)H are influenced and show particular trends
      from monomer to the target molecule in the cluster due to the contribution of
      target molecule to classic N-H...O, and non-classic S-H...O and S-H...S types of
      HB interactions. On the other hand, atoms in molecules (AIM) analyses confirm the
      presence of HB interactions and rationalize the observed EFG trends. The results
      indicate different contribution of various nuclei to HB interactions in the
      cluster where O2 and N1 have major contributions. The EFG tensors as well as AIM
      analysis at the H6 site show that the N1-H6...O2 HB undergoes a significant
      change from 30 to 298 K where changes in other N-H...O interactions are almost
      negligible. There is a good agreement between the calculated (14)N NQR parameters
      and reported experimental data.

PMID- 19168277
TI  - Normal plasma antithrombin activity in patients with relapsing-remitting and
      secondary progressive multiple sclerosis.
AB  - OBJECTIVE: Multiple sclerosis (MS) is an inflammatory disease characterized by
      multifocal areas of central nervous system (CNS) demyelination. Activation of
      coagulation factors and fibrin deposition are observed around CNS blood vessels
      in experimental autoimmune encephalomyelitis, an animal model of MS. Antithrombin
      (AT) is a potent anticoagulant with remarkable anti-inflammatory properties, and
      its inhibitory effects on coagulation and inflammation may play a role in the
      pathogenesis and clinical course of MS. We studied the association between plasma
      AT activity and clinical forms of MS. PATIENTS AND METHODS: A total of 69
      patients, 37 with relapsing-remitting and 32 with secondary progressive MS, were
      included in the study. A control group (CG) of 34 normal subjects was also
      studied. Plasma AT activity (Stachrom ATIII) was quantified using a chromogenic
      activity assay with normal reference values ranging from 70% to 120% of AT
      activity. RESULTS: We found no difference between plasma AT levels in patients
      and those in CG. We also found no association of AT levels with activity of
      disease, duration of disease progression, level of neurological disability, and
      treatment. CONCLUSION: We found no association between plasma AT activity and
      RRMS or SPMS. It remains to be studied whether exists or not an association
      between abnormal plasma AT activity and other MS forms.

PMID- 19168278
TI  - 1,4-Naphthoquinone is a potent inhibitor of human cancer cell growth and
      angiogenesis.
AB  - Angiogenesis inhibitors are beneficial for the prevention and treatment of
      angiogenesis-dependent diseases including cancer. Vitamin K2 and K3, which are
      naphthoquinone derivatives, inhibit angiogenesis. We examined the anti-cancer and
      anti-angiogenic effects of naphthoquinones and its structurally related
      compounds. Among these 13 compounds, 1,4-naphthoquinone strongly inhibited both
      human colon cancer cell (HCT116) growth and angiogenesis. To clarify the anti
      angiogenic mechanism, the effects of 1,4-naphthoquinone on human umbilical vein
      endothelial cell (HUVEC) tube formation, proliferation and chemotaxis were
      examined. Consequently, 1,4-naphthoquinone inhibited HUVEC functions. These
      results suggest that 1,4-naphthoquinone may be useful to cancer therapy.

PMID- 19168279
TI  - Synergy of 5-aza-2'-deoxycytidine (DAC) and paclitaxel in both androgen-dependent
      and -independent prostate cancer cell lines.
AB  - To determine the synergy of 5-aza-2'-deoxycytidine (DAC) and paclitaxel (PTX)
      against prostate carcinoma (PC) cells by isobolographic analysis. We demonstrated
      that DAC could significantly increase the susceptibility of PC cells to PTX, and
      confirmed the synergy of DAC and PTX. DAC enhanced the PTX induced up-regulation
      of caspase activity and antiproliferative effect, resulting in an increase of
      cells in subG1 and G2/M phases. In addition, the synergy was observed in both
      androgen-dependent and -independent PC cell lines. It suggested that combination
      chemotherapy with DAC and PTX might be a new strategy to improve the clinical
      response rate of PC.

PMID- 19168280
TI  - Targeting calcium/calmodulin-dependence kinase I and II as a potential anti
      proliferation remedy for endometrial carcinomas.
AB  - Calcium/calmodulin-dependent kinase (CaMK) I and II expression in endometrial
      cancer cells correlates with the malignant potential of this tumor, and CaMKI and
      II are potential therapeutic targets in endometrial cancer. CaMKI and II
      expression was significantly associated with PCNA-labeling index, clinical stage,
      histological grade, the presence of invasion to greater than one-half the
      myometrium, and clinical outcome. All endometrial cancer cell lines examined were
      sensitive to the growth-inhibitory effect of KN-93, a membrane-permeant CaMKs
      selective inhibitor that is competitive with calmodulin. KN-93 induced the G0/G1
      arrest and apoptosis, rising hopes that KN-93 may become a useful treatment for
      endometrial cancers.

PMID- 19168281
TI  - Rosiglitazone reduces cell invasiveness by inducing MKP-1 in human U87MG glioma
      cells.
AB  - We sought to investigate the molecular mechanisms by which rosiglitazone (RGZ)
      inhibits cell invasion in human glioma cells. In this study, we found that RGZ
      attenuated MMP-2 protein levels, MMP-2 gelatinolytic activity, and cell
      invasiveness through a PPAR-gamma independent pathway. RGZ increased mitogen
      activated protein kinase phosphatase-1 (MKP-1) expression. The addition of
      triptolide (a diterpenoid triepoxide, which blocked MKP-1 induction) abolished
      the inhibitory effects by RGZ. Furthermore, we demonstrated that the knock down
      of MKP-1 by MKP-1 specific small interference RNA reversed the reduction of MMP-2
      secretion, and of cell invasiveness by RGZ. In contrast, the stable expression of
      MKP-1 in glioma cell lines decreased MMP-2 activity and cell invasiveness. These
      results suggest that RGZ may mediate the inhibitory effects through MKP-1
      induction. Thus, MKP-1 could be a potential target in glioma therapy.

PMID- 19168282
TI  - t(3;21)(q22;q22) leading to truncation of the RYK gene in atypical chronic
      myeloid leukemia.
AB  - The analysis of a small number of patients with atypical chronic myeloid leukemia
      showing balanced chromosomal translocations has revealed diverse tyrosine kinase
      fusion genes, most commonly involving FGFR1, PDGFRA, PDGFRB, JAK2, and ABL. We
      present a case of aCML with a 3q22;21q22-translocation that led to truncation of
      the receptor-like tyrosine kinase (RYK) gene and its juxtaposition with sequences
      from chromosome 21 including the ATP5O gene coding for a mitochondrial ATP
      synthase. The resulting fusion was not in frame, however, which is why we
      speculate that an abrogated RYK gene product rather than a chimeric protein might
      be the leukemogenic result.

PMID- 19168283
TI  - Novel modeling concept for evaluating the effects of cadmium and copper on
      heterotrophic growth and lysis rates in activated sludge process.
AB  - A new modeling concept to evaluate the effects of cadmium and copper on
      heterotrophic growth rate constant (mu(H)) and lysis rate constant (b(H)) in
      activated sludge was introduced. The oxygen uptake rate (OUR) was employed to
      measure the constants. The results indicated that the mu(H) value decreased from
      4.52 to 3.26 d(-1) or by 28% when 0.7 mg L(-1) of cadmium was added. Contrarily
      the b(H) value increased from 0.31 to 0.35 d(-1) or by 11%. When adding 0.7 mg L(
      1) of copper, the mu(H) value decreased to 2.80 d(-1) or by 38%. The b(H) value
      increased to 0.42 d(-1) or by 35%. After regression, the inhibitory effect was in
      a good agreement with non-competitive inhibition kinetic. The inhibition
      coefficient values for cadmium and copper were 1.82 and 1.21 mg L(-1),
      respectively. The relation between the b(H) values and heavy metal concentrations
      agreed with exponential type well. The heavy metal would enhance b(H) value.
      Using these data, a new kinetic model was established and used to simulate the
      degree of inhibition. It was evident that not only the inhibitory effect on mu(H)
      but also that the enhancement effect on b(H) should be considered when heavy
      metal presented.

PMID- 19168284
TI  - Simultaneous removal of chromium and leather dye from simulated tannery effluent
      by photoelectrochemistry.
AB  - The feasibility of the photobleaching of a leather acid dye, acid red 151,
      simultaneously to degradation of anionic surfactant, Tamol, and reduction of
      Cr(VI) to the less toxic Cr(III) was investigated by photoelectrocatalytic
      oxidation. The best experimental conditions were found to be pH 2.0 and 0.1 mol
      L(-1) sodium sulfate when the nanoporous Ti/TiO2 photo anode was biased at +1.0 V
      and submitted to UV-irradiation. The photoelectrocatalytic oxidation promotes
      100% discoloration, reducing around 98-100% of Cr(VI) and achieving an abatement
      of 95% of the original total organic carbon. The effect of pH, the applied
      potential, the Cr(VI) concentration and the complexation reaction between Cr(VI)
      and acid red dye were evaluated as to their effect on the kinetics of the
      reaction.

PMID- 19168285
TI  - Colour and COD removal of disperse dye solution by a novel coagulant: application
      of statistical design for the optimization and regression analysis.
AB  - The investigation presented here focussed on the steel industrial wastewater
      (SIWW) FeCl(3) rich as an original coagulant to remove the synthetic textile
      wastewater. Response surface methodology was used to study the cumulative effect
      of the various parameters namely, coagulant dosage, initial pH of dye solution,
      dye concentration and to optimize the process conditions for the decolourization
      and COD reduction of disperse blue 79 solution. For obtaining the mutual
      interaction between the variables and optimizing these variables, a 2(3) full
      factorial central composite rotatable design using response surface methodology
      was employed. The efficiencies of decolourization and COD reduction for disperse
      blue 79 solution were accomplished at optimum conditions as 99% and 94%,
      respectively.

PMID- 19168286
TI  - Effect of impregnation of activated carbon with chelating polymer on adsorption
      kinetics of Pb2+.
AB  - The effects of polyethyleneimine (PEI) impregnation on the Pb(2+) adsorption
      kinetics of palm shell-activated carbon and pH profile of bulk solution were
      investigated. Adsorption data were fitted to four established adsorption kinetics
      models, namely, pseudo-first-order, pseudo-second-order, Elovich equation and
      intraparticle diffusion. It was found that PEI impregnation at 16.68 and 29.82
      wt% PEI/AC increased the Pb(2+) uptake rate while the opposite was observed for
      PEI impregnation at 4.76 and 8.41 wt% PEI/AC. The increased uptake rates were due
      to higher concentration of PEI molecules on the surface of clogged pores as well
      as varying pore volumes. The adsorption kinetics data fitted the pseudo-second
      order model better than the pseudo-first-order model, implying chemisorption was
      the rate-controlling step. The bulk solution pH generally showed an increasing
      trend from the use of virgin to PEI-impregnated activated carbon.

PMID- 19168287
TI  - Influence of structural parameters on magnetoresistive properties of CuFeNi melt
      spun ribbons.
AB  - The microstructure of Cu(80)Fe(10)Ni(10) (at%) granular ribbon was investigated
      by means of atom probe tomography (APT). A granular system is composed of
      magnetic precipitates embedded in a non-magnetic matrix. In this ribbon, the
      magnetic precipitates have a diameter smaller than 5nm in the as-spun state, and
      their crystallographic structure is very similar to the one of the matrix, which
      makes it difficult to characterize them using conventional techniques. Those data
      are of great importance to understand the magnetic and the transport behaviour of
      these ribbons. Using atom probe tomography, a 3D reconstruction of the
      microstructure of the as-spun and annealed ribbons was achieved and a precise
      characterization of the compositions of the two phases and of the composition
      profile at interfaces was carried out. In the as-spun state the composition of
      the matrix is Cu(89)Fe(3)Ni(8), the one of the precipitates is
      Cu(30)Fe(40)Ni(30). Upon annealing, the precipitates get enriched in iron. After
      annealing at 600 degrees C for 24h, the measured compositions are close to the
      one predicted by Thermocalc, with Cu(94)Fe(1)Ni(5) for the matrix and
      Cu(5)Fe(64)Ni(31) for the precipitates.

PMID- 19168288
TI  - Transmission of Cytauxzoon felis to a domestic cat by Amblyomma americanum.
AB  - Cytauxzoon felis was transmitted to a domestic cat by Amblyomma americanum. The
      infection was produced by the bite of A. americanum adults that were acquisition
      fed as nymphs on a domestic cat that naturally survived infection of C. felis.
      Fever, inappetence, depression, and lethargy were first noted 11 days post
      infestation (dpi). Pale mucus membranes, splenomegaly, icterus, and dyspnea were
      also observed during the course of the disease. The body temperature of the
      experimentally infected C. felis cat was subnormal from 16 dpi until 24 dpi when
      it returned to within normal limits. All clinical signs of cytauxzoonsis began to
      resolve by 23 dpi when the cat became subclinically infected with C. felis. The
      cat developed a marked, regenerative anemia beginning by 13 dpi and reached a
      nadir at 20 dpi before recovering. A moderate neutrophilia and marked
      lymphocytosis also developed between 18 and 26 dpi. Schizonts of C. felis were
      observed in spleen aspirates of the infected cat at 15 dpi. DNA of C. felis was
      amplified by real-time PCR starting 17 dpi and piroplasms of C. felis were first
      noted by light microscopy 18 dpi. Dermacentor variabilis, Ixodes scapularis, and
      Rhipicephalus sanguineus were also tested in a similar manner at the same time
      but did not transmit C. felis. Prior to the present study, only D. variabilis had
      been shown experimentally to transmit infection of C. felis. This is the first
      report of C. felis being transmitted by A. americanum. The transmission of C.
      felis infection from one domestic cat to another indicates that domestic cats
      subclinically infected with C. felis may be a reservoir of infection for naive
      domestic cats.

PMID- 19168289
TI  - Mobile telephone induced burn.

PMID- 19168290
TI  - Vibration may be a potential non-pharmacological treatment of osteoarthritis.

PMID- 19168291
TI  - Plasma exchange therapy holds promise in the management of advanced cancer.
AB  - Cancer is now emerging as the second most common cause of death worldwide.
      Currently the most widely used treatments for solid cancer are surgery,
      chemotherapy, radiotherapy and hormone therapy, all of which are of limited
      effects in improvement of the survival. It is well-established that circulating
      factors are involved in the development of cancer. And plasma exchange is a well
      established therapeutic procedure commonly used in many autoimmune diseases
      through the elimination of pathologic mediators, including auto-antibodies,
      complement components, and cytokines. Thus, we hypothesize that plasma exchange
      therapy alone or in combination with the routine therapeutics should be
      considered as an alternative for the present treatments. Future clinical studies
      are needed to validate the hypothesis.

PMID- 19168292
TI  - N-methyl-D-aspartate receptor antagonists for migraine: a potential therapeutic
      approach.
AB  - Migraine is one of the most common neurological disorders and still remains
      incurable. New targets for potential pharmacological intervention should be
      explored and evaluated for effective long-term management of patients with
      migraine. N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion
      channels widely expressed in the central nervous system. NMDAR activation has
      been suggested to be implicated in trigeminovascular system and cortical
      spreading depression, which are involved in the mechanisms of migraine. Thus, it
      is reasonable to infer that NMDAR antagonists may provide a potentially novel
      therapeutic approach to the treatment of migraine. So far, no controlled clinical
      trial has been published that examines the efficacy of NMDAR antagonist for
      migraine prophylaxis. It is to be hoped that further studies of NMDAR
      antagonists, especially NR2B-selective and low-affinity antagonists, will enable
      the potential of these drugs to be fully tested.

PMID- 19168293
TI  - Successful human scar regeneration by topical iodine: a case report: an interim
      (3.5 year) summary.
AB  - Control of regeneration and wound healing are scientific and clinical objectives.
      In 1997, topical Lugol's iodine solution applied daily for 3 days to a 50 year
      old facial scar lead to hyperemic scar tissue. As a working hypothesis, the
      author proposed topical iodine could initiate, control and complete human scar
      regeneration. In 2005, after collecting three more surgical scars, topical iodine
      applications began. Within 3 days all four scars started regenerating. Stopping
      topical iodine halted the process. Within a week an appropriate adult scar
      formed. Digital cameras recorded events. Regeneration is complex and slow. Its
      appearance depends on whether scar is covered with plastic or open. Iodine's
      chemical properties are discussed along with their reaction with epithelial
      cells. As there are no visible signs detectable changes from oral iodine on
      regeneration, details of iodine staining are more thoroughly described. Not all,
      but most important results are presented. Topical iodine induces hair growth in
      and around scars. Hair is regeneration's workhorse, moving purposefully in all
      directions under arrector pili muscle power delivering regenate material
      accurately to scar tissues and coordinating centers. In addition, hair repeatedly
      self amputates possibly strengthening regenerating tissues. Two types of regenate
      material show under plastic wrap: white and globular. The white regenate appears
      and behaves somewhat like snow, but can be yellow, green or brown depending
      iodine content. The globular form of regenate material maybe derived from white
      regenate material with hair's help. Globular regenate material is larger,
      nondescript, variable in size and color (depends on iodine content) and seemed
      usually associated with hair. There are two centrally placed coordinating centers
      5 mm apart on major scars. Wrist centers have a palpable, but not visible ridge,
      between them whereas abdominal centers do not. Wrist centers lasted through all
      regeneration of the wrist scar, whereas abdominal centers were only present for
      about 18 months before falling off. This paper summarizes and adds to previous
      preliminary reports. The 50 year old scar regenerated completely 2 years ago.
      Small experiments on regeneration are possible because it is a slow process and
      more importantly can be stopped and started at will. These results support the
      proposed hypothesis topical iodine initiates, controls, and completes human scar
      regeneration.

PMID- 19168294
TI  - Paracortical axillary sentinel lymph node ectopic breast tissue.
AB  - Benign glandular inclusions in axillary lymph nodes are uncommon, and their
      presence in axillary sentinel lymph nodes is exceptionally rare. The possibility
      of over-staging due to misinterpretation of glandular inclusions as metastatic
      carcinoma is a concerning issue. We present a 54-year-old female with high grade
      ductal carcinoma in-situ undergoing simple mastectomy with sentinel lymph node
      biopsy. Permanent sections of the sentinel lymph node revealed scarce naked small
      glands without surrounding stroma scattered in the paracortex in the superficial
      level. Deeper levels showed glands spanning a much larger area (2mm), with bland
      ducts and tubules separated by abundant stroma. The myoepithelial layer was
      visible and was immunohistochemically confirmed. A final diagnosis of benign
      ectopic breast tissue within an axillary sentinel lymph node was rendered.
      Previous studies described axillary sentinel lymph nodes with glandular
      inclusions separated by stroma or subcapsular in location. It has been suggested
      that paracortical location and absence of stroma are characteristics of
      metastasis. As demonstrated in our report, benign inclusions may be paracortical
      and lack surrounding stroma. We recommend that glandular inclusions should be a
      diagnostic consideration for cases in which paracortically located naked glands
      do not histologically resemble the corresponding primary tumor.

PMID- 19168295
TI  - Freedom from local and regional failure of contralateral neck with ipsilateral
      neck radiotherapy for node-positive tonsil cancer: results of a prospective
      management approach.
AB  - PURPOSE: To review the outcomes of a prospective management approach using
      ipsilateral neck radiotherapy in the treatment of node-positive squamous cell
      carcinoma of the tonsil with a well-lateralized primary lesion. METHODS AND
      MATERIALS: Between August 2003 and June 2007, 20 patients who presented with
      squamous cell carcinoma of the tonsil, without involvement of the base of the
      tongue or midline soft palate, and with Stage N1-N2b disease were prospectively
      treated with radiotherapy to the primary site and ipsilateral neck. In addition,
      18 patients received concurrent chemotherapy. The actuarial freedom from
      contralateral nodal and in-field progression was determined. Acute and late
      toxicity were prospectively evaluated using the National Cancer Institute Common
      Terminology Criteria for Adverse Events, version 3, and Radiation Therapy
      Oncology Group criteria. RESULTS: The nodal disease was Stage N1 in 4 patients,
      N2a in 3 patients, and N2b in 13 patients. At a median follow-up 19 months
      (range, 12-40), no in-field or contralateral nodal recurrences had been observed.
      The 2-year freedom from distant metastasis rate was 87.4%. The actuarial 2-year
      disease-free and overall survival rates were both 79.5%. Late Radiation Therapy
      Oncology Group grade 2 xerostomia occurred in 1 patient (5%). No late Grade 3 or
      greater toxicity was observed. No patient was feeding tube dependent at their
      last follow-up visit. CONCLUSION: In carefully selected patients with node
      positive, lateralized tonsillar cancer, treatment of the ipsilateral neck and
      primary site does not appear to increase the risk of contralateral nodal failure
      and reduces late morbidity compared with historical controls. Although the
      outcomes with ipsilateral radiotherapy in the present series were promising,
      these findings require longer follow-up and validation in a larger patient
      cohort.

PMID- 19168296
TI  - The dynamic tumor bed: volumetric changes in the lumpectomy cavity during breast
      conserving therapy.
AB  - PURPOSE: To characterize the magnitude of volume change in the postoperative
      tumor bed before and during radiotherapy, and to identify any factors associated
      with large volumetric change. METHODS AND MATERIALS: Thirty-six consecutive
      patients with early-stage or preinvasive breast cancer underwent breast
      conserving therapy at our institution between June 2006 and October 2007.
      Computed tomography (CT) scans of the breast were obtained shortly after surgery,
      before the start of radiotherapy (RT) for treatment planning, and, if applicable,
      before the tumor bed boost. Postoperative changes, seroma, and surgical clips
      were used to define the tumor bed through consensus agreement of 3 observers
      (B.P., D.I., and J.L.). Multiple variables were examined for correlation with
      volumetric change. RESULTS: Between the first and last scan obtained (median
      time, 7.2 weeks), the tumor bed volume decreased at least 20% in 86% of patients
      (n = 31) and at least 50% in 64% of patients (n = 23). From the postoperative
      scan to the planning scan (median time, 3 weeks), the tumor bed volume decreased
      by an average of 49.9%, or approximately 2.1% per postoperative day. From
      planning scan to boost scan (median interval, 7 weeks), the median tumor bed
      volume decreased by 44.6%, at an average rate of 0.95% per postoperative day. No
      single factor was significantly associated with a change in tumor bed volume
      greater than 20%. CONCLUSIONS: The average postlumpectomy cavity undergoes
      dramatic volumetric change after surgery and continues this change during RT. The
      rate of change is inversely proportional to the duration from surgery. In this
      study no factors studied predicted large volumetric change.

PMID- 19168298
TI  - Predicting the visitation of carcasses by carrion-related insects under different
      rates of degree-day accumulation.
AB  - Common assumptions in forensic entomology are that insects visit and colonize
      carcasses following a predictable sequence, and that this succession varies among
      seasons. However, currently available evidence for insect succession on
      decomposing bodies is essentially descriptive and, to our knowledge, the fine
      scale predictability of insect succession with respect to seasons has never been
      confirmed statistically. In this study, we test these assumptions through the
      sampling of carrion-related insects attracted to pig carcasses. The study was
      carried out during the summer and fall of 2006 in rural fields of New Brunswick,
      Canada. Of the five species of carrion-related insects with high enough
      occurrence on carcasses to allow modelling, three showed predictable occurrence
      with respect to degree-day accumulation and seasonal effects. This demonstrates
      that the occurrence probability of some carrion-related insects on carcasses can
      be estimated from meteorological records even across seasons with different rates
      of degree-day accumulation. As opposed to the prevailing idea that adult insects
      are not reliable for post-mortem interval estimation, the adults of some species
      exhibited a specific pattern of visitation that could be determined and used in
      forensic investigations. It is stressed, however, that the statistical
      predictability of species occurrence must be assessed before any species is
      considered as a post-mortem interval indicator.

PMID- 19168297
TI  - Breast-conserving treatment in the elderly: long-term results of adjuvant
      hypofractionated and normofractionated radiotherapy.
AB  - PURPOSE: To evaluate the long-term cause-specific survival (CSS), locoregional
      recurrence-free survival (LRFS), and metastases-free survival (MFS) in elderly
      breast cancer patients receiving adjuvant normofractionated (NF) or
      hypofractionated (HF) radiotherapy (RT). METHODS AND MATERIALS: Between 1995 and
      1999, 367 women aged >or=70 years with nonmetastatic Stage T1 or T2 tumors were
      treated by breast-conserving surgery and adjuvant RT at the Institut Curie. They
      underwent wide tumor excision with or without lymph node dissection followed by
      RT. They received either a NF-RT schedule, which delivered a total dose of 50 Gy
      (25 fractions, 5 fractions weekly) to the whole breast, followed by a boost to
      the tumor bed when indicated, or a HF-RT schedule, which delivered a total dose
      of 32.5 Gy (five fractions of 6.5 Gy, once weekly) with no subsequent boost. The
      HF-RT schedule was indicated for the more elderly patients. RESULTS: A total of
      317 patients were in the NF-RT group, with 50 in the HF-RT group. The median
      follow-up was 93 months (range, 9-140). The 5- and 7-year CSS, LRFS, and MFS
      rates were similar in both groups. The 5-year NF-RT and HF-RT rate was 96% and
      95% for CSS, 95% and 94% for LRFS, and 94% and 95% for MFS, respectively. The 7
      year NF-RT and HF-RT rate was 93% and 87% for CSS, 93% and 91% for LRFS, and 92%
      and 93% for MFS, respectively. CONCLUSION: According to the findings from this
      retrospective study, the HF-RT schedule is an acceptable alternative to NF-RT for
      elderly patients. However, large-scale prospective randomized trials are needed
      to confirm these results.

PMID- 19168299
TI  - A fraud management system architecture for next-generation networks.
AB  - This paper proposes an original architecture for a fraud management system (FMS)
      for convergent. Next-generation networks (NGNs), which are based on the Internet
      protocol (IP). The architecture has the potential to satisfy the requirements of
      flexibility and application-independency for effective fraud detection in NGNs
      that cannot be met by traditional FMSs. The proposed architecture has a thorough
      four-stage detection process that analyses billing records in IP detail record
      (IPDR) format - an emerging IP-based billing standard - for signs of fraud. Its
      key feature is its usage of neural networks in the form of self-organising maps
      (SOMs) to help uncover unknown NGN fraud scenarios. A prototype was implemented
      to test the effectiveness of using a SOM for fraud detection and is also
      described in the paper.

PMID- 19168300
TI  - The color(s) of human hair--forensic hair analysis with SpectraCube.
AB  - Human hair is among the most common kind of evidence secured at crime scenes.
      Although DNA analysis through STR-typing is possible in principle, it is not very
      promising for telogenic hair or single hairs. For the mixed traces frequently
      found in practice, composed of different hair from an unknown number of
      individuals, mtDNA sequencing of each individual hair seems to be the only
      possible, even if technically elaborate, solution. If it were possible to pool
      all hair belonging to an individual prior to DNA analysis, then this effort could
      not only be reduced, but the number of hair for an STR-approach could also be
      increased. Although it is possible to examine hair microscopically, this method
      must be considered unsuitable for pooling, since the results depend strongly on
      examiner experience, and the hair cannot always be correctly attributed to an
      individual. The goal of this study was to develop an objective non-DNA
      contaminative pooling method for hair. To this end, the efficacy of spectral
      imaging as a method of obtaining information--beyond that obtained from a purely
      microscopic and morphological approach--for the identification of individuals was
      investigated. Three hairs each from 25 test persons (female: 18; male: 7) were
      examined with a SpectraCube-System and a light microscope. Six spectra were
      calculated for each hair, and the hairs from each individual were not only
      compared to each other, but also to those of the other individuals. From a
      forensic vantage, the examination showed, in particular, that individuals, whose
      hair could not be distinguished on the basis of morphology, could also not be
      accurately distinguished with the SpectraCube. The intra-individual differences
      were, in part, greater than the inter-individual differences. Altogether, the
      study shows that a person's hair color, as perceived, is composed of many
      naturally different, individual colors.

PMID- 19168301
TI  - Growth disturbance of frontal lobe in BCECTS presenting with frontal dysfunction.
AB  - A considerable proportion of children with benign childhood epilepsy with
      centrotemporal spikes (BCECTS) have increasingly been found to show
      neuropsychiatric deficits such as cognitive impairment and impulsivity, possibly
      associated with frontal lobe dysfunctions. We performed 3-dimensional magnetic
      resonance imaging (MRI)-based brain volumetry to characterize serial changes in
      frontal and prefrontal lobe volumes and compare volumetric changes with clinical
      symptoms. Serial changes in regional cerebral volumes were measured in a 5-year
      old boy with BCECTS. Seizures were not easily controlled, and he demonstrated
      oromotor deficits, cognitive impairments and behavioral problems. Cognitive and
      behavioral deficits persisted even after remission of seizure disorder and
      oromotor deficits. Two BCECTS patients (5-6 years old) without neuropsychological
      disorders served as typical BCECTS, and nine normal subjects (4-10 years old)
      served as controls. Volumes of the frontal and prefrontal lobes were determined
      using a workstation, and prefrontal to frontal lobe volume ratio was calculated.
      Frontal and prefrontal lobe volumes showed no growth even after remission of
      seizure disorders. Prefrontal to frontal lobe volume ratio reduced slightly even
      after remission of both seizure disorders and EEG abnormalities. The result
      suggests that BCECTS presenting with atypical course may be associated with
      frontal lobe dysfunction resulting in cognitive and behavioral deficits.

PMID- 19168302
TI  - Physical exercise during the adolescent period of life increases hippocampal
      parvalbumin expression.
AB  - In order to investigate whether physical exercise during development would
      promote changes the calcium-binding protein parvalbumin (PV) expression in the
      hippocampal formation, we performed an immunostaining study after an aerobic
      exercise program in rats during adolescent period of life. Wistar rats were
      submitted to daily exercise program in a treadmill between postnatal day 21 and
      60. Running time and speed were gradually increased during the subsequent days
      until 18m/min for 60min. After the aerobic exercise program, animals of all
      groups were killed and PV immunostaining procedures were performed. The results
      showed significant increase of protein level in the hippocampal formation and PV
      immunoreactive neurons in CA1 and CA2/CA3 regions of rats submitted to exercise
      when compared with control rats. This finding indicates that aerobic exercise
      program during adolescent period promotes neuroplastic changes in hippocampal
      formation.

PMID- 19168303
TI  - Diversity analysis of magnetotactic bacteria in Lake Miyun, northern China, by
      restriction fragment length polymorphism.
AB  - Magnetotactic bacteria (MTB) synthesize intracellular nano-scale crystals of
      magnetite or greigite within magnetosomes. MTB are ubiquitous in limnic and
      marine environments. In order to understand the diversity of MTB better, sediment
      samples were examined from Lake Miyun near Beijing by restriction fragment length
      polymorphism (RFLP). First, in silico analysis was used to evaluate the
      effectiveness of 12 sets of restriction endonucleases for distinguishing MTB
      sequences retrieved from the GenBank database. It was found that the tested
      restriction endonucleases had different power in the ability to differentiate the
      operational taxonomic units (OTUs) of MTB. Specifically, of the 12 sets of
      enzymes, MspI plus RsaI was found to be the most effective for correctly
      differentiating the OTUs of selected MTB sequences and it could detect 16 OTUs
      with appropriate OTUmin and OTUmax values (96.7% and 97.7%, respectively). The
      MspI plus RsaI RFLP analysis was then utilized to investigate the diversity of
      MTB in Lake Miyun sediment and it identified 8 OTUs (74.5% of the whole library)
      as MTB. Among these, 5 were affiliated to Alphaproteobacteria, while the rest
      belonged to the Nitrospira phylum. Interestingly, OTUs C, D and I displayed 91.8
      98.4% similarity to "Magnetobacterium bavaricum". Together, these results
      demonstrated that the MspI plus RsaI RFLP analysis was useful for studying the
      diversity and change in community composition of uncultivated MTB from
      environmental samples.

PMID- 19168304
TI  - Using magnetic resonance imaging to monitor CH4 hydrate formation and spontaneous
      conversion of CH4 hydrate to CO2 hydrate in porous media.
AB  - Magnetic resonance imaging was used to monitor and quantify methane hydrate
      formation and exchange in porous media. Conversion of methane hydrate to carbon
      dioxide hydrate, when exposed to liquid carbon dioxide at 8.27 MPa and
      approximately 4 degrees C, was experimentally demonstrated with MRI data and
      verified by mass balance calculations of consumed volumes of gases and liquids.
      No detectable dissociation of the hydrate was measured during the exchange
      process.

PMID- 19168305
TI  - Differences in time to detection and recovery of Mycobacterium spp. between the
      MGIT 960 and the BacT/ALERT MB automated culture systems.
AB  - Mycobacterium sp. recovery and time to detection were compared in the MGIT 960
      and BacT/ALERT MB automated broth culture systems. The MGIT 960 demonstrated
      shorter time to detection (13.5 versus 25.2 days) and greater sensitivity (100%
      versus 66.6%) for recovery of the Mycobacterium tuberculosis complex than the
      BacT/ALERT MB system.

PMID- 19168306
TI  - The effect of physician triage on emergency department length of stay.
AB  - BACKGROUND: Emergency Department (ED) overcrowding is a serious public health
      issue, but few solutions exist. OBJECTIVES: We sought to determine the impact of
      physician triage on ED length of stay for discharged and admitted patients, left
      without-being-seen (LWBS) rates, and ambulance diversion. METHODS: This was a pre
      post study performed using retrospective data at an urban, academic tertiary
      care, Level I trauma center. On July 11, 2005, physician triage was initiated
      from 1:00 p.m. to 9:00 p.m., 7 days a week. An additional physician was placed in
      triage so that the ED diagnostic evaluation and treatment could be started in
      waiting room patients. Using the hospital information system, we obtained
      individual patient data, ED and waiting room statistics, and diversion status
      data from a 9-week pre-physician triage (May 11, 2005 to July 10, 2005) and a 9
      week physician triage (July 11, 2005 to September 9, 2005) period. RESULTS: We
      observed that overall ED length of stay decreased by 11 min, but this decrease
      was entirely attributed to non-admitted patients. No difference in ED length of
      stay was observed in admitted patients. LWBS rates decreased from 4.5% to 2.5%.
      Total time spent on ambulance diversion decreased from 5.6 days per month to 3.2
      days per month. CONCLUSION: Physician triage was associated with a decrease in
      LWBS rates, and time spent on ambulance diversion. However, its effect on ED LOS
      was modest in non-admitted ED patients and negligible in admitted patients.

PMID- 19168307
TI  - Horner's syndrome, hoarseness, and unsteady gait.

PMID- 19168308
TI  - Effectiveness of management of diabetic ketoacidosis in the emergency department
      of a general hospital in Greece.

PMID- 19168309
TI  - Toxic methemoglobinemia due to Ibuprofen: report of a pediatric case.

PMID- 19168310
TI  - D-dimer measurement and laboratory feedback.

PMID- 19168312
TI  - Clopidogrel use in ST-elevation myocardial infarction (STEMI).

PMID- 19168313
TI  - Large-volume paracentesis: a fast, convenient, and safe technique.
AB  - BACKGROUND: Ascites is a common complication of liver cirrhosis, malignancy,
      cardiac failure, pancreatitis, and tuberculosis, with cirrhosis of the liver
      being the most common cause. Onset of ascites in cirrhosis of the liver is
      associated with worsened quality of life, increased risk of spontaneous bacterial
      peritonitis, and renal failure. Management of ascites caused by cirrhosis
      requires sodium restriction in diet, sodium excretion with diuretics and, in
      refractory cases, large volume paracentesis. TECHNIQUE: We describe a simple
      adjustment to the standard paracentesis technique that does not require
      additional equipment or manpower. CONCLUSION: Removing over 5 L of ascitic fluid
      can become a time-consuming and labor-intensive process. We describe a setup that
      makes this commonly performed procedure fast, convenient, and safe.

PMID- 19168314
TI  - Sonography streamlines the diagnosis in hand injuries with small foreign bodies.

PMID- 19168315
TI  - Emergency medicine resident performed bedside ultrasonography of the gallbladder
      in non-fasted healthy volunteers.
AB  - BACKGROUND: Gallbladder ultrasonography is a commonly performed test in the
      emergency department. It is unknown whether a non-fasting state alters the
      visualization of the gallbladder by emergency medicine (EM) residents.
      OBJECTIVES: We conducted this study to determine whether EM residents are able to
      visualize the gallbladder in volunteers who have recently consumed a fatty meal.
      METHODS: This study used a prospective, single-blinded, randomized controlled
      design. Initial scans were performed on fasting volunteers. A fatty meal was then
      consumed. Thirty minutes after eating, a different resident, who was unaware of
      whether the volunteer had eaten or fasted, performed a second scan. To control
      for operator bias, 10% of subjects remained fasting between scans. Student's
      paired-samples t-test, Pearson's chi-squared, and McNemar test were determined as
      appropriate. RESULTS: A total of 92 scans from 46 volunteers were analyzed. EM
      residents were able to visualize the gallbladder in all 40 pre-prandial scans
      (100%) and all 40 post-prandial scans (100%). Gallbladder area as measured in the
      longitudinal axis decreased 20% from a mean baseline of 11.58 +/- 4.86 cm(2) (95%
      confidence interval [CI] 11.17-12.98) to 9.2 +/- 5.04 cm(2) (95% CI 7.74-10.66, p
      = 0.0009) after food intake. Total time to scan for the fasting volunteers (110.2
      s, 95% CI 84.34-136) did not change significantly from non-fasting volunteers
      (129.7 s, 95% CI 110.29-149.01, p = 0.153). CONCLUSIONS: EM residents are able to
      visualize the gallbladder in non-fasted healthy volunteers.

PMID- 19168316
TI  - Bringing journal club to the bedside in the form of a critical appraisal blog.

PMID- 19168317
TI  - Provider-patient interaction in rural Cameroon--how it relates to the patient's
      understanding of diagnosis and prescribed drugs, the patient's concept of
      illness, and access to therapy.
AB  - OBJECTIVE: This cross-sectional survey examines the relation between provider
      patient interaction and several patient-outcomes in a rural health district in
      Cameroon. METHODS: We used structured patient interviews and the Roter
      Interaction Analysis System (RIAS) for analysis of audio-recorded consultations.
      RESULTS: Data from 130 primary care consultations with 13 health-care providers
      were analysed. 51% of patients correctly named their diagnoses after the
      consultation; in 47% of prescribed drugs patients explained correctly the
      purpose. Patients' ability to recall diagnoses was related to the extent of
      clarity a provider used in mentioning it during consultation (recall rates: 87.5%
      if mentioned explicitly, 56.7% if mentioned indirectly and 19.2% if not mentioned
      at all; p<0.001). Two thirds of patients were able to describe their concept of
      illness before the consultation, but only 47% of them mentioned it during
      consultations. On average patients who mentioned their disease concept were faced
      with more remarks of disapproval from providers (1.73 vs 0.63 per consultation;
      p<0.01). Although 41% of patients admitted problems with financial resources to
      buy prescribed drugs, discussion about financial issues was very rare during
      consultations. Providers issued financial questions in 32%, patients in 21% of
      consultations. CONCLUSION: This study shows that provider-patient interaction in
      primary health care in a rural Cameroon district deserves more attention. It
      might improve the patients' knowledge about their health condition and support
      them in beneficial health behaviour. PRACTICE IMPLICATIONS: Our findings should
      encourage providers to give more medical explanation, to discuss patients' health
      beliefs in a non-judgmental manner, and to consider financial issues more
      carefully.

PMID- 19168318
TI  - Peripheral leucocyte count variations in rectal cancer treatment.
AB  - AIM: Mortality after curative surgery for rectal cancer is increased if surgery
      is not performed within a week of completed short course radiotherapy. A link to
      the suppression of leucocytes after neoadjuvant radiotherapy has been suggested.
      This study investigates the effects of radiotherapy on peripheral leucocyte
      counts, complications and survival. METHOD: Patient data variables from a
      retrospective database (Local and National Swedish Registries) of a total of 926
      consecutive patients treated for rectal cancer disease at two surgical units
      (1993-2004) were analysed for leucocyte counts and mortality. In all 310 patients
      received radiotherapy. Mean follow-up time was 2.8 years. RESULTS: There was a
      marked suppression of leucocytes in the irradiated groups coupled with a
      reduction in leucocyte response to surgery (p<0.05) compared to non-irradiated
      patients. Long course radiotherapy resulted in a better postoperative leucocyte
      response. Irradiated patients with a low post/preoperative leucocyte ratio had
      higher complication rates. No association between leucocyte response and survival
      was seen in the irradiated group. CONCLUSIONS: Postoperative leucocytosis is
      impaired after neoadjuvant radiotherapy, independent of latency period to
      surgery. Irradiated patients with a suppression of leucocyte response had
      significantly higher complication rates. The true extent of survival could not be
      measured in radiotherapy groups due to the short median follow-up period.

PMID- 19168319
TI  - [Weak opioids. Pain and Locoregional Anesthesia Committee and the Standards
      Committee of the French Society of Anesthesia and Intensive Care].

PMID- 19168320
TI  - [Osborn J wave and cardiac rythm disorders].

PMID- 19168321
TI  - [Neglected children: birth, life and survival].
AB  - Child neglect leads to numerous and serious consequences. The physical and
      neurophysiological development can be altered by the lack of stimulation or via a
      chronic stress which increases the production of cortisol. Gradually, psychomotor
      and cognitive deficits can appear. The emotions can be deeply touched and cause
      dysfunctional social relationship, ranging from withdrawal to aggressiveness.
      Primary care health practitioners have a role to play in the screening of risk
      situations and long term follow-up of the families. The interventions should
      ideally begin early, be participatory and based on an enhancement of the parent
      child relationship.

PMID- 19168322
TI  - Direct measurement of proximal isovelocity surface area by real-time three
      dimensional color Doppler for quantitation of aortic regurgitant volume: an in
      vitro validation.
AB  - OBJECTIVE: The proximal isovelocity surface area (PISA) method is useful in the
      quantitation of aortic regurgitation (AR). We hypothesized that actual
      measurement of PISA provided with real-time 3-dimensional (3D) color Doppler
      yields more accurate regurgitant volumes than those estimated by 2-dimensional
      (2D) color Doppler PISA. METHODS: We developed a pulsatile flow model for AR with
      an imaging chamber in which interchangeable regurgitant orifices with defined
      shapes and areas were incorporated. An ultrasonic flow meter was used to
      calculate the reference regurgitant volumes. A total of 29 different flow
      conditions for 5 orifices with different shapes were tested at a rate of 72
      beats/min. 2D PISA was calculated as 2pi r(2), and 3D PISA was measured from 8
      equidistant radial planes of the 3D PISA. Regurgitant volume was derived as PISA
      x aliasing velocity x time velocity integral of AR/peak AR velocity. RESULTS:
      Regurgitant volumes by flow meter ranged between 12.6 and 30.6 mL/beat (mean 21.4
      +/- 5.5 mL/beat). Regurgitant volumes estimated by 2D PISA correlated well with
      volumes measured by flow meter (r = 0.69); however, a significant underestimation
      was observed (y = 0.5x + 0.6). Correlation with flow meter volumes was stronger
      for 3D PISA-derived regurgitant volumes (r = 0.83); significantly less
      underestimation of regurgitant volumes was seen, with a regression line close to
      identity (y = 0.9x + 3.9). CONCLUSION: Direct measurement of PISA is feasible,
      without geometric assumptions, using real-time 3D color Doppler. Calculation of
      aortic regurgitant volumes with 3D color Doppler using this methodology is more
      accurate than conventional 2D method with hemispheric PISA assumption.

PMID- 19168323
TI  - Assessment of temporal heterogeneity and regional motion to identify wall motion
      abnormalities using treadmill exercise stress three-dimensional echocardiography.
AB  - BACKGROUND: Exercise 3-dimensional echocardiography (3DE) may avoid the problem
      of poorly matched pre- and post-exercise 2-dimensional echocardiograms (2DE), and
      contraction front mapping (CFM) may be used to quantify the temporal homogeneity
      of contraction. We compared 3DE with 2DE for identification of angiographically
      significant disease. METHODS: Conventional 2DE and 3DE at rest and peak stress
      were performed in 110 patients (78 men, aged 60 +/- 11 years) who underwent
      angiography within 6 months. Offline assessment of CFM was performed
      qualitatively (delayed regional relaxation in a coronary territory) and
      quantitatively (difference in regional and global contraction delays from rest to
      peak in individual segments). The accuracy of each test was calculated for
      identification of 70% or more diameter angiographic stenoses. RESULTS: Patients
      were excluded for nondiagnostic stress (n = 12) or poor-quality 3DE (n = 8). Time
      until end of 2DE acquisition was 58 +/- 25 seconds, and time until end of 3DE
      (taken after 2DE) was 109 +/- 55 seconds. Receiver operating characteristic
      analyses were used to define normal cutoff ranges of contraction delays for the
      following coronary territories: left anterior descending (<or=10%), left coronary
      artery (<or=10%), right coronary artery (<or=11%), and overall (<or=10%). The
      concordance between angiography and qualitative CFM (63%) was similar to
      quantitative CFM (70%). The sensitivity of wall motion assessment at 3DE (40%)
      was lower than CFM (55%, P = .04) and 2DE (83%, P < .01) at comparable levels of
      specificity (65%, 84%, and 78%). CONCLUSION: Although the higher specificity of
      3DE may represent avoidance of false-positives from off-axis imaging, the
      sensitivity of 3DE is insufficient for clinical use. Analysis of the temporal
      distribution of contraction may be more sensitive than 3D wall motion assessment
      for identification of ischemia at exercise 3DE.

PMID- 19168324
TI  - Correlation of tissue Doppler and two-dimensional speckle myocardial velocities
      and comparison of derived ratios with invasively measured left ventricular
      filling pressures.
AB  - BACKGROUND: There are a paucity of data comparing spectral and color tissue
      Doppler (TD) with non-Doppler, speckle-based myocardial velocities, and it is
      unknown how early transmitral diastolic velocity/mitral annular velocity (E/Ea)
      calculated using speckle velocities compares with TD-derived E/Ea. METHODS: We
      measured systolic (Sa), Ea, and late diastolic (Aa) myocardial velocities using
      these 3 methods and compared calculated E/Ea with invasively measured left
      ventricular (LV) hemodynamics. Consecutive patients referred for cardiac
      catheterization were imaged, and LV pre-A contraction pressure was measured by
      retrograde aortic cardiac catheterization. RESULTS: Fifty patients (22 women,
      44%) were studied with a mean age of 54 +/- 10 years and a mean LV ejection
      fraction of 48% +/- 19%. Speckle and color TD Sa, Ea, and Aa were significantly
      lower than spectral TD velocities, resulting in higher E/Ea values compared with
      spectral TD E/Ea. Spectral TD E/Ea (R = 0.65, P < .001), color TD E/Ea (R = 0.69,
      P < .001), and speckle E/Ea (R = 0.76, P < .001) all correlated with LV pre-A
      pressure. Different cutoff values were needed for spectral TD, color TD, and
      speckle E/Ea to predict LV pre-A pressure >or= 15 mm Hg; spectral E/Ea > 14 (area
      under the curve [AUC] = 0.87, P < .001, sensitivity = 83%, specificity = 77%),
      color E/Ea > 16 (AUC = 0.89, P < .0001, sensitivity = 79%, specificity = 81%),
      and speckle E/Ea > 18 (AUC = 0.87, P < .0001, sensitivity = 88%, specificity =
      74%; P = not significant for comparisons between the groups). CONCLUSION:
      Spectral TD, color TD, and speckle imaging measure different velocities, and
      consequently different cutoff values are needed for E/Ea to predict invasively
      measured LV filling pressure.

PMID- 19168325
TI  - Left ventricular strain patterns in dilated cardiomyopathy predict response to
      cardiac resynchronization therapy: timing is not everything.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is not uniformly helpful in
      heart failure, and the determination of baseline dyssynchrony does not improve
      its success rate. The aim of this study was to develop prediction rules for
      successful CRT on the basis of mechanical strain patterns of left ventricular
      function rather than just the timing of activation. METHODS: Seventy-six patients
      had CRT devices implanted from 2003 to 2006 and underwent echocardiography before
      and after device implantation. RESULTS: Responders (n = 44), determined by
      >or=10% improvement in ejection fraction and/or >or=15% decrease in end-systolic
      volume, and nonresponders (n = 32) had similar baseline clinical and
      echocardiographic characteristics, which improved only in responders.
      Resynchronization was achieved in both groups. Two-dimensional speckle-tracking
      longitudinal strain patterns were correlated with response. The absence of
      passive compliant segments (>or=+5% holosystolic stretching) was 98% sensitive,
      88% specific, and had positive and negative predicting values of 91% and 97%,
      respectively, for response. Adding the presence of lateral delay to this model
      increased sensitivity to 100% and specificity to 94%. CONCLUSION: Left
      ventricular strain patterns are highly predictive of response to CRT.

PMID- 19168326
TI  - A randomized, double-blind, placebo-controlled study comparing the efficacy and
      safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the
      dental impaction pain model.
AB  - Assessment of postoperative sequelae following the removal of an impacted third
      molar has been used in clinical pharmacology to evaluate the relative efficacy of
      various analgesic, anti-inflammatory drugs. This study included 150 patients with
      impacted lower third molars. They were randomly sorted to receive ibuprofen,
      paracetamol, betamethasone, serratiopeptidase or placebo. Evaluation of efficacy
      was made using tape measurement (for swelling), visual analogue scale (for pain
      evaluation), mouth opening ability and oral temperature. The effect of treatment
      on hematological parameters, bleeding, wound healing and requirement for rescue
      medication was also studied. Peak pain scores were observed approximately 5-6
      hours after the operation. Betamethasone showed significant analgesic activity
      from day 1. Ibuprofen and betamethasone were significantly more effective than
      placebo in reducing swelling. Trismus was least with betamethasone. A significant
      rise in temperature on the operated side occurred only on day 1 in all the
      groups. Serratiopeptidase did not showed significant analgesic and anti
      inflammatory action. Mild-to-moderate adverse effects were reported.

PMID- 19168327
TI  - Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem
      cells.
AB  - Microvascular reconstruction is the state-of-the-art in many fields of defect
      surgery today. Currently, reconstruction of large bony defects involves
      harvesting of autologous bone causing donor site morbidity and risk of infection.
      Specifically, utilizing autologous adipose stem cells (autoASCs), large
      quantities of cells can be retrieved for cell therapy applications and the risk
      of tissue rejection is diminished. The authors describe the first case report of
      a microvascular custom-made ectopic bone flap employing good manufacturing
      practice (GMP) level ASCs. The patient underwent a hemimaxillectomy due to a
      large keratocyst. After 36 months of follow-up, the defect was reconstructed with
      a microvascular flap using autoASCs, beta-tricalcium phosphate and bone
      morphogenetic protein-2. ASCs were isolated and expanded in clean room facilities
      according to GMP standards and were characterized in vitro. After 8 months of
      follow-up, the flap had developed mature bone structures and vasculature and was
      transplanted into the defect area. Postoperative healing has been uneventful, and
      further rehabilitation with dental implants has been started. The in vitro
      characterization demonstrated multipotentiality and mesenchymal stem cell
      characteristics in ASCs. This is the first clinical case where ectopic bone was
      produced using autoASCs in microvascular reconstruction surgery and it will pave
      way for new clinical trials in the field.

PMID- 19168328
TI  - Physical and mental health-related quality of life among older people with
      schizophrenia.
AB  - OBJECTIVE: Since the time of Kraeplin, schizophrenia has been thought of as a
      disorder with progressive deterioration in functioning. An important aspect of
      functioning is both physical and mental health-related quality of life (HRQoL).
      The objective of this study was to examine the relationship of age to both mental
      and physical aspects of HRQoL in individuals with schizophrenia as compared to
      normal comparison subjects (NCs). METHODS: Middle-aged and older community
      dwelling patients with schizophrenia (N=486) were compared to NCs (N=101). Health
      related quality of life was measured using the SF-36 Physical Health and Mental
      Health Component scores. The relationship between age and HRQoL was examined
      using linear regressions. In addition, we performed exploratory analyses to
      examine the effects of confounding variables on this relationship, and to examine
      the effects of age on SF-36 subscales. RESULTS: Patients with schizophrenia had
      lower SF-36 Physical and Mental Health Component scores than NCs, and these
      differences persisted after adjusting for the age difference between the two
      groups. The relationship between age and mental, but not physical, HRQoL was
      significantly different between the patients with schizophrenia and the NCs.
      Specifically, older age was associated with higher mental HRQoL among patients
      with schizophrenia, but not among the NCs. This difference remained significant
      after examining multiple potential confounding demographic and clinical
      variables. CONCLUSIONS: This study found that older age was associated with
      greater mental health quality of life. Longitudinal studies are warranted to
      confirm our finding, and to examine potential mechanisms responsible for possible
      improvement in mental HRQoL with age.

PMID- 19168329
TI  - Remission in schizophrenia: results from a 1-year follow-up observational study.
AB  - OBJECTIVES: This study used the Remission in Schizophrenia Working Group
      operational-severity criteria to, a) provide descriptive data on prevalence and
      stability of symptomatic remission, b) attempt a criterion (concurrent)
      validation of this measure of remission, and c) explore correlates of remission
      stability. METHODS: From an unselected sample of 1010 stable outpatients with
      schizophrenia (DSM-IV-TR), a subgroup of 452 (44.8%) in symptomatic remission was
      followed for 1 year. Of these, 376 were re-evaluated in a research diagnostic
      assessment. In addition to relevant sociodemographic and clinical data, measures
      included symptoms, depression, functioning, social cognition, attitudes towards
      medication, and quality of life. Estimates of point prevalence are provided.
      Correlates of remission were identified by logistic regression. RESULTS:
      Symptomatic remission at baseline correlated with better premorbid adjustment,
      better social cognition, good treatment compliance, younger age, the absence of
      comorbid substance abuse, current or past participation in psychotherapy, and a
      lack of past participation in rehabilitation. After 1 year, 338 out of the 376
      (89.9%) patients re-evaluated were found again in remission. In this assessment,
      better premorbid adjustment, good treatment compliance, and improvement of
      depressive symptoms and social cognition during follow-up again correlated with
      remission. CONCLUSIONS: The results of this study suggest that symptomatic
      remission (as defined above) has considerable criterion validity and is a
      realistic goal in the treatment of schizophrenia. Attaining and sustaining
      remission may warrant better clinical and functional outcomes for patients.

PMID- 19168330
TI  - Epicutaneous sensitization with a protein antigen induces Th17 cells.
AB  - BACKGROUND: Th17 is a newly identified effector T cell lineage which plays a
      central role in many human inflammatory diseases and experimental animal models.
      Epicutaneous sensitization with a protein antigen has been proven to induce a Th2
      predominant immune response and lead to development of atopic diseases in a
      murine protein-patch model. OBJECTIVE: We sought to assess the generation of Th17
      cells in epicutaneous sensitization with a protein antigen and its regulation by
      environmental elements and genetic background. METHODS: BALB/c, C57BL/6, and
      DO11.10 mice were epicutaneously immunized by patch application of the following:
      ovalbumin alone, or co-administration of one of TLR ligands, irritant, hapten or
      superantigens. IL-17 and IL-22 contents in supernatants of in vitro reactivation
      culture of lymph nodes cells were determined by ELISA. Frequency of IL-17
      secreting CD4 T cells was measured by ELISPOT. RESULTS: Small but significant
      amounts of IL-17 and IL-22 could be detected in supernatants of in vitro
      reactivation culture of lymph nodes cells of mice receiving patch application of
      ovalbumin. ELISPOT assay for IL-17 also revealed low frequency of IL-17-secreting
      CD4 T cells in lymph nodes cells in ovalbumin group. All TLR ligands tested
      including agonists for TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9 as well as many
      environmental elements including irritant, hapten and superantigen could further
      promote the generation of Th17 cells. In addition, C57BL/6 mice generate less
      Th17 cells than BALB/c mice in epicutaneous sensitization. CONCLUSION: This study
      demonstrates Th17 generation and its regulation by environmental elements and
      genetic background to a protein antigen by epicutaneous route.

PMID- 19168331
TI  - Phenotypic and genotypic characterisation of antimicrobial resistance in faecal
      bacteria from 30 Giant pandas.
AB  - To study the prevalence of antimicrobial resistance in faecal bacteria from Giant
      pandas in China, 59 isolates were recovered from faecal pats of 30 Giant pandas.
      Antimicrobial susceptibility testing of the isolates was performed by the
      standardised disk diffusion method (Kirby-Bauer). Of the 59 study isolates,
      32.20% were resistant to at least one antimicrobial and 16.95% showed multidrug
      resistant phenotypes. Thirteen drug resistance genes [aph(3')-IIa, aac(6')-Ib,
      ant(3'')-Ia, aac(3)-IIa, sul1, sul2, sul3, tetA, tetC, tetM, cat1, floR and cmlA]
      were analysed using four primer sets by multiplex polymerase chain reaction
      (PCR). The detection frequency of the aph(3')-IIa gene was the highest (10.17%),
      followed by cmlA (8.47%). The genes aac(6')-Ib, sul2 and tetA were not detected.
      PCR products were confirmed by DNA sequence analysis. The results revealed that
      multidrug resistance was widely present in bacteria isolated from Giant pandas.

PMID- 19168332
TI  - WITHDRAWN: Synergistic interaction of aciclovir and a helicase-primase inhibitor,
      BAY 57-1293, against herpes simplex virus type 1.
AB  - This article has been withdrawn at the request of the author(s). 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- 19168333
TI  - Systemic colistin use in children without cystic fibrosis: a systematic review of
      the literature.
AB  - The increasing incidence of multidrug-resistant (MDR) Gram-negative infections
      necessitates the use of neglected antibiotics such as colistin, even in the
      paediatric field. The objective of this review was to evaluate the available
      clinical evidence regarding the effectiveness and safety of systemic colistin in
      children without cystic fibrosis (CF). Relevant articles were identified from
      PubMed, Cochrane and Scopus databases. Ten case series and fifteen case reports,
      including a total of 370 children, were eligible for inclusion in this systematic
      review. Only 17 of the children were included in studies published after 1977. A
      total of 326 children received colistin for the treatment of infections and 44
      for surgical prophylaxis or prophylaxis of infections in burns patients.
      Regarding the clinical outcome, 271 of 311 children included in the identified
      cases series were evaluable. From these 271 children, 235 (86.7%) were cured of
      the infection, 10/271 (3.7%) improved, 6/271 (2.2%) deteriorated and 20/271
      (7.4%) died. Fourteen (70%) of the 20 deaths were attributed to the infection. No
      infection occurred in the 44 reported children with burns or surgical morbidity
      who received colistin for prophylaxis. Of these 44 children, 9 (20.5%) died; all
      deaths were attributed to co-morbidity. Nephrotoxicity occurred in 10/355 (2.8%)
      of the evaluable children in cases series included in this review. Most of the
      identified relevant case reports focused on treatment complications. The
      available evidence, mainly from old case series, suggests that systemic colistin
      is an effective and acceptably safe option for the treatment of children without
      CF who have MDR Gram-negative infections.

PMID- 19168335
TI  - Changes in regional cerebral blood flow after body image exposure in eating
      disorders.
AB  - Relationships of 'perceptual distortion' and 'cognitive evaluation' components of
      body image disturbances to brain activity were investigated. Changes in regional
      cerebral blood (rCBF) of nine patients with anorexia nervosa restrictive type
      (AN), 13 patients with bulimia nervosa purging type (BN) and 12 controls
      following three experiments with single photon emission computed tomography
      (SPECT) were compared: at rest, following a landscape video presentation (neutral
      stimulus), and after their filmed body image (positive stimulus) exposure. Body
      distortion was measured with the Silhouette test and body dissatisfaction with
      the Body Shape Questionnaire (BSQ). Patients with AN showed a hyperactivation of
      the left parietal and right superior frontal from neutral to positive stimulus.
      Patients with BN showed a hyperactivation of the right temporal and right
      occipital areas. Changes in BSQ responses were associated with changes in the
      right inferior frontal and right temporal rCBF, whereas changes in body
      distortion were related to the left parietal. The activation of the right
      temporal after the own body image exposure might be in accordance with the
      aversive events' response. Functional abnormalities in AN might be related to the
      storage of a distorted prototypical image of the body in the left parietal lobe.

PMID- 19168334
TI  - Neuroanatomical differences between familial and sporadic schizophrenia and their
      parents: an optimized voxel-based morphometry study.
AB  - Symptomatic differences have been reported between patients with familial and
      sporadic schizophrenia. The present study examined neuroanatomical differences
      between the two subgroups and their parents using voxel-based morphometry. High
      resolution T1-weighted images were obtained using 3 Tesla magnetic resonance
      imaging from 20 patients with schizophrenia (familial subgroup, n=10; sporadic
      subgroup, n=10), 20 of their parents (familial subgroup, n=10; sporadic subgroup,
      n=10) and 20 healthy volunteers. Gray matter density (GMD) was compared between
      groups on a voxel-by-voxel basis. Compared with the sporadic patients, the
      familial patients had significantly reduced GMD in the thalamus bilaterally.
      Reduction of GMD in bilateral thalami was also found in familial parents in
      comparison with sporadic parents. Compared with controls, both familial and
      sporadic patients had lower GMD involving bilateral insula, right temporal lobe,
      right occipital lobe, left lenticular nucleus and right cerebellum. However, only
      familial patients showed lower GMD than controls in the right thalamus. Compared
      with controls, only familial parents showed lower GMD in the right insula
      extending to the right temporal lobe and the right parietal lobule. The present
      data suggest that familial schizophrenia is associated with more severe
      structural abnormalities than sporadic schizophrenia, especially in the thalamus.

PMID- 19168336
TI  - Mechanical property analysis of stored red blood cell using optical tweezers.
AB  - The deformation of human red blood cells subjected to direct stretching by
      optical tweezers was analyzed. The maximum force exerted by optical tweezers on
      the cell via a polystyrene microbead 5microm in diameter was 315pN. Digital image
      correlation (DIC) method was introduced to calculate the force and the
      deformation of the cell for the first time. Force-extension relation curves of
      the biconcave cell were quantitatively assessed when erythrocytes were stored in
      Alsever's Solution for 2 days, 5 days, 7 days and 14 days respectively.
      Experiment results demonstrated that the deformability of red blood cells was
      impaired with the stored time.

PMID- 19168337
TI  - l-Arginine supplementation enhances eNOS expression in experimental model of
      hypercholesterolemic rabbits aorta.
AB  - INTRODUCTION: Diminished bioavailability of nitric oxide is crucial in
      endothelial dysfunction and the development of atherosclerosis. Several studies
      have found that l-arginine as a nitric oxide (NO) donor has beneficial effect in
      prevention of atherosclerosis, but the mechanism is not completely known. We
      hypothesized that increased endothelial nitric oxide synthase (eNOS) and/or
      decreased inducible NOS (iNOS) expressions might be involved in the preventive
      effects of l-arginine in hypercholesterolemic rabbits. METHODS: Seventeen male
      rabbits were divided randomly in two groups. They received rabbits chow
      supplemented with 1% cholesterol (group 1, n=8) and the other group received also
      l-arginine (3% in drinking water) (group 2, n=9) for 1 month. Blood samples were
      obtained before and after the experiment. At the end of experiment, the aortas
      were harvested. The serum levels of cholesterol and low-density lipoproteins
      (LDL) were measured. The intima/media thickness (IMT) ratio was measured and the
      determination of fatty streak formation was done with the aid of light
      microscopy. eNOS and iNOS expression in aorta were studied with
      immuohistochemistery. RESULTS: The IMT ratio in first group having fatty streaks
      was 0.287+/-0.15. No fatty streak lesion was detected in l-arginine-treated
      group. The results also indicated that eNOS expression (intensity) in aortas was
      significantly higher in l-arginine-treated group (group 1: 13.62+/-2.7 and group
      2: 21.77+/-2.8; p<0.05), but no significant difference was observed for iNOS
      expression between the groups. CONCLUSION: The expression of eNOS plays an
      important role in the protection of the vessel wall from atherosclerosis. l
      Arginine in drinking water has a beneficial effect in the enhancement of eNOS
      protein expression.

PMID- 19168338
TI  - A new opportunity for radiotherapy research in the UK.

PMID- 19168339
TI  - Neutrophilic asthma has different radiographic features to COPD and smokers.
AB  - BACKGROUND: Neutrophilic asthma and COPD are obstructive airway diseases common
      in older age and have a characteristic airway inflammation with neutrophilic
      bronchitis. The structural differences between neutrophilic asthma and COPD have
      not been investigated. The aim of this study was to examine the airway and
      parenchymal abnormalities using high resolution computed tomographic (HRCT)
      scanning in participants with neutrophilic asthma, COPD and smoking controls.
      METHODS: Participants (neutrophilic asthma (n=10), COPD (n=17) and smoking
      controls (n=8)) underwent clinical assessment and sputum induction. HRCT of the
      chest was performed and independently scored by a radiologist blinded to the
      subject group using a modified Bhalla scoring system. RESULTS: Participants were
      of a similar age and those with COPD had a similar degree of airflow obstruction
      to those with neutrophilic asthma. The pattern of radiographic abnormalities
      differed between groups. Abnormal bronchial wall thickening was significantly
      more common in neutrophilic asthma, compared to COPD or smoking controls.
      Emphysema was greatest in the COPD group, and not recorded as a feature of
      neutrophilic asthma. FEV(1)% predicted was negatively associated with bronchial
      wall thickening and consolidation while KCO% predicted was negatively associated
      with the total emphysema score. Bronchiectasis was minimal in all groups.
      CONCLUSION: The pattern of radiographic lung abnormality in neutrophilic asthma
      differs significantly from COPD, and resembles asthma. Neutrophilic asthma is a
      distinct inflammatory subtype of asthma with a different pathogenesis to COPD.

PMID- 19168340
TI  - An economic analysis of pharmacological treatment of COPD in Spain.
AB  - BACKGROUND: COPD is a prevalent disease that generates high use of resources. The
      objective of this study was to quantify the economic consequences of non
      adherence to GOLD guidelines for the management of COPD patients. METHOD: An
      economic model was generated to compare different scenarios of observed vs.
      expected costs of COPD treatment. A pooled analysis of data derived from a
      systematic review of studies describing treatment of COPD in Spain was combined
      with drug costs (using different assumptions) to obtain the observed cost of COPD
      treatment. An expected cost was obtained with the minimum and maximum treatment
      intensity derived from the GOLD recommendations. RESULTS: A total of 8 studies
      were identified, comprising 6339 patients. Average medication cost of COPD
      patients was estimated as being between euro 1218 and euro 1314 per patient per
      year, higher than the ideal expected average cost (between euro 1007 and euro
      1021 per patient/year). Thus, implementation of guidelines would result in a mean
      reduction of euro 198-euro 293 per patient/year. Sensitivity analysis showed that
      about 13% of patients had higher treatment costs than the maximum expected cost.
      This proportion is much higher in moderately/severely affected patients than in
      mildly affected patients (28.0% and 11.1%, respectively). CONCLUSIONS: Treatment
      of COPD allows for the identification of areas of inefficiency. An improvement in
      the adherence to the GOLD guidelines would imply potential savings of medication
      costs of about 20% of the observed costs.

PMID- 19168341
TI  - Actin nucleation and elongation factors: mechanisms and interplay.
AB  - Cells require actin nucleators to catalyze the de novo assembly of filaments and
      actin elongation factors to control the rate and extent of polymerization.
      Nucleation and elongation factors identified to date include Arp2/3 complex,
      formins, Ena/VASP, and newcomers Spire, Cobl, and Lmod. Here, we discuss recent
      advances in understanding their activities and mechanisms and new evidence for
      their cooperation and interaction in vivo. Earlier models had suggested that
      different nucleators function independently to assemble distinct actin arrays.
      However, more recent observations indicate that the construction of most cellular
      actin networks depends on the activities of multiple actin assembly-promoting
      factors working in concert.

PMID- 19168342
TI  - 'Kiddie drugs' and controlled pleasure: recreational use of dexamphetamine in a
      social network of young Australians.
AB  - BACKGROUND: This article explores the recreational use of diverted
      dexamphetamine, a pharmaceutical stimulant, amongst a social network of young
      adults (aged 18-31 years) in Perth, Western Australia (WA). Prior epidemiological
      research indicates that there are high levels of dexamphetamine prescription, and
      use of diverted dexamphetamine, in this jurisdiction. Little research exists on
      the social contexts of diverted dexamphetamine use in Australia or overseas.
      METHODS: Ethnographic fieldwork was conducted over 18 months amongst a network of
      approximately 60 young adults who regularly used psychostimulants. Data
      collection involved participant observation conducted in natural settings
      including nightclubs and private parties. In-depth interviews were also conducted
      with 25 key contacts which explored drug use histories and themes emerging from
      fieldwork. RESULTS: The use of diverted dexamphetamine, or 'dexies', was
      prevalent amongst the social network and integrated into local drug practices.
      The paper explores the ways in which dexamphetamine use is rationalised,
      negotiated and represented in the context of the use of alcohol and other
      psychostimulants such as methamphetamine and ecstasy. Two key aspects are
      emphasised. First, dexamphetamine use is seen as insignificant by network members
      and is positioned as 'safer' in relation to the use of other drugs by virtue of
      its pharmaceutical status. Second, dexamphetamine plays an instrumental role in
      facilitating the pursuit of 'controlled pleasure' via the heavy consumption of
      alcohol and other drugs. CONCLUSION: The findings of the paper have implications
      for harm reduction policy. In particular, dexamphetamine use facilitates heavy
      drinking and polydrug use amongst young adults, which may increase the harms
      associated with such use. Further, current interventions targeting young
      psychostimulant users, which emphasise their adulterated and illegal nature, may
      inadvertently contribute to the cultural construction of dexamphetamine as a
      relatively 'safe' drug.

PMID- 19168343
TI  - Characteristics of wood-fiber plastic composites made of recycled materials.
AB  - This study investigates the feasibility of using recycled high density
      polyethylene (rHDPE), polypropylene (rPP) and old newspaper (rONP) fiber to
      manufacture experimental composite panels. The panels were made through air
      forming and hot press. The effects of the fiber and coupling agent concentration
      on tensile, flexural, internal bond properties and water absorption and thickness
      swelling of wood-fiber plastic composites were studied. The use of maleated
      polypropylene as coupling agent improved the compatibility between the fiber and
      both plastic matrices and mechanical properties of the resultant composites
      compared well with those of non-coupled ones. Based on the findings in this work,
      it appears that recycled materials can be used to manufacture value-added panels
      without having any significant adverse influence on board properties. It was also
      found that composites with rHDPE provided moderately superior properties,
      compared with rPP samples.

PMID- 19168344
TI  - The use of LCA in selecting the best MSW management system.
AB  - This paper focuses on the study of eleven environmental impact categories
      produced by several municipal solid waste management systems (scenarios)
      operating on a provincial scale in Southern Italy. In particular, the analysis
      takes into account 12 management scenarios with 16 management phases for each
      one. The only difference among ten of the scenarios (separated kerbside
      collection of all recyclables, glass excepted, composting of putrescibles, RDF
      pressed bales production and incineration, final landfilling) is the percentage
      of separated collection varying in the range of 35-80%, while the other two
      scenarios, for 80% of separate collection, consider different alternatives in the
      disposal of treatment residues (dry residue sorting and final landfilling or
      direct disposal in landfill). The potential impacts induced on the environmental
      components were analysed using the life cycle assessment (LCA) procedure called
      "WISARD" (Waste Integrated System Assessment for Recovery and Disposal). Paper
      recycling was the phase with the greatest influence on avoided impacts, while the
      collection logistics of dry residue was the phase with the greatest influence on
      produced impacts. For six impact categories (renewable and total energy use,
      water, suspended solids and oxydable matters index, eutrophication and hazardous
      waste production), for high percentages of separate collection a management
      system based on recovery and recycling but without incineration would be
      preferable.

PMID- 19168345
TI  - Single-crystal CeO2 nanocubes used for the direct electron transfer and
      electrocatalysis of horseradish peroxidase.
AB  - A new horseradish peroxidase (HRP) third-generation electrochemical biosensor
      based on ceria nanocubes (CeO(2)-NCs) and chitosan (Chit) was developed. The
      single-crystalline, uniform and size-controlled CeO(2)-NCs have been synthesized
      by hydrothermal method. HRP was immobilized in CeO(2)-NCs and Chit film on the
      glass carbon electrode (HRP/CeO(2)/Chit/GCE). Compared with HRP-chitosan modified
      electrode (HRP/Chit/GCE), HRP/CeO(2)/Chit/GCE exhibited a pair of more obvious
      redox peaks at -0.348 V (versus Ag/AgCl). Experimental results indicate CeO(2)
      NCs greatly promoted the electron transfer between HRP and GCE. The immobilized
      HRP exhibited direct electrochemical behavior toward the reduction of hydrogen
      peroxide (H(2)O(2)). The resulting biosensor showed a linear range of 1-150
      microM and a detection limit of 0.26 microM estimated at a signal-to-noise ratio
      of 3. Stability and reproducibility of the biosensor were also studied. The
      biological activity of HRP immobilizing in the composite film was characterized
      by UV-vis and FTIR spectra.

PMID- 19168346
TI  - PMMA biosensor for nucleic acids with integrated mixer and electrochemical
      detection.
AB  - This paper discusses the design, microfabrication and use of an electrochemical
      biosensor based on a polymer substrate for cost effectiveness and disposability.
      As model analyte, amplified hsp70 mRNA from Cryptosporidium parvum was chosen.
      Microfluidic channels were fabricated in poly(methyl methacrylate) (PMMA) using
      hot embossing with a copper master. The electrochemical transducer, an
      interdigitated ultramicroelectrode array (IDUA) was also realized directly on the
      PMMA surface. First, the unstructured PMMA surface was UV functionalized. An 8
      min UV treatment resulted in a carboxylic acid density of approximately 8
      nmol/cm(2) on the PMMA surface. The surface carboxylic acid groups were then
      conjugated to cystamine using water-soluble carbodiimide chemistry. Gold (200 nm)
      was then evaporated onto the thiol-functionalized surface. Using standard
      photolithography techniques, the IDUA containing 10 microm wide electrodes with 5
      microm gaps was then formed followed by a gold etch. The PMMA surface containing
      the microchannel was subsequently bonded to the PMMA surface containing the IDUA
      using UV-assisted thermal bonding. The additional UV treatment also served to
      decrease the water contact angle of the surface from 62.5 degrees +/-0.7 degrees
      to 48.4 degrees +/-0.2 degrees thus, aiding with the capillary flow in the
      device. The hsp70 mRNA was isolated from C. parvum oocysts and amplified using
      nucleic acid sequence-based amplification (NASBA). The amplicon was detected in a
      sandwich hybridization assay with capture probe-coated superparamagnetic beads
      and reporter probe-tagged liposomes. The liposomes entrapped potassium
      ferro/ferrihexacyanide to enable amperometric quantification of the amplicon on
      the IDUA. Amplified mRNA from only 1 oocyst was detectable with this PMMA
      biosensor. The final detection device measured approximately 10 mm x 40 mm x 3 mm
      and contained two detection channels for dual analyses.

PMID- 19168347
TI  - Amperometric S-nitrosothiol sensor with enhanced sensitivity based on
      organoselenium catalysts.
AB  - A new S-nitrosothiol (RSNO) detection strategy based on an electrochemical sensor
      is described for rapidly estimating levels of total RSNOs in blood and other
      biological samples. The sensor employs a cellulose dialysis membrane covalently
      modified with an organoselenium catalyst that converts RSNOs to NO at the distal
      tip of an amperometric NO sensor. The sensor is characterized by very low
      detection limits (<20 nM), good long-term stability, and can be employed for the
      rapid detection of total low-molecular-weight (LMW) RSNO levels in whole blood
      samples using a simple standard addition method. A strategy for detecting
      macromolecular RSNOs is also demonstrated via use of a transnitrosation reaction
      with added LMW thiols allowing the estimation of total RSNO levels in blood. The
      sensor is shown to exhibit high selectivity over nitrosamines and nitrite. Such
      RSNO detection is potentially useful to reveal correlation between blood RSNO
      levels and endothelial cell dysfunction, which often is associated with
      cardiovascular diseases.

PMID- 19168348
TI  - A Prime minister managed to attract elderly men in a Belgian Euromelanoma
      campaign.

PMID- 19168349
TI  - A randomised, double-blind, phase II study of two doses of pemetrexed in the
      treatment of platinum-resistant, epithelial ovarian or primary peritoneal cancer.
AB  - PURPOSE: We conducted a randomised phase II study to assess the safety and
      efficacy of standard versus high-dose pemetrexed in platinum-resistant epithelial
      ovarian cancer (PR-EOC). The expression of ten genes was also examined as
      potential biomarkers of pemetrexed/platinum activity. PATIENTS AND METHODS:
      Patients received pemetrexed 500mg/m(2) (Pem500) or 900mg/m(2) (Pem900) on day 1
      of each 21-d cycle. Responses were defined per RECIST for measurable disease or
      by Gynaecologic Cancer Intergroup (GCIG) CA-125 criteria for non-measurable
      disease. RESULTS: Of 102 patients randomised, 98 were evaluable for toxicity (47
      Pem500, 51 Pem900) and 91 were evaluable for efficacy (43 Pem500, 48 Pem900) of
      whom 68 had measurable disease and 23 had CA-125-defined disease. The overall RR
      was 9.3% (95% CI: 2.6-22.1%) on Pem500 and 10.4% (95% CI: 3.5-22.7%) on Pem900.
      The median progression-free survival (PFS) was 2.8 months on both arms, and the
      median survival was 11.9 and 10.3 months, respectively. Lower mRNA expression of
      excision repair cross-complementation group 1 (ERCC1) and reduced folate carrier
      1 (RFC1) were associated with longer PFS and time to treatment failure,
      respectively. Grade 3/4 toxicities, including fatigue, nausea and vomiting, were
      numerically greater on Pem900. Pemetrexed-related SAEs occurred in 17% and 28% of
      Pem500 and Pem900 patients, respectively. CONCLUSIONS: Pemetrexed has activity in
      PR-EOC equivalent to other agents in platinum-resistant disease; however, Pem500
      has the preferable toxicity profile. ERCC1 and RFC1 may merit examination as
      predictive biomarkers in PR-EOC.

PMID- 19168350
TI  - Discovery of mu-opioid selective ligands derived from 1-aminotetralin scaffolds
      made via metal-catalyzed ring-opening reactions.
AB  - A series of 1-aminotetralin scaffolds was synthesized via metal-catalyzed ring
      opening reactions of heterobicyclic alkenes. Small libraries of amides and amines
      were made using the amino group of each scaffold as a handle. Screening of these
      libraries against human opioid receptors led to the identification of (S)-(S)
      5.2a as a high-affinity selective mu ligand (IC(50)mu=5 nM, kappa=707 nM,
      delta=3,795 nM) displaying mu-agonist/antagonist properties due to its partial
      agonism (EC(50)=2.6 microM; E(max)=18%).

PMID- 19168351
TI  - Novel potent inhibitors of hepatitis C virus (HCV) NS3 protease with cyclic
      sulfonyl P3 cappings.
AB  - Extensive SAR studies of the P3 capping group led to the discovery of a series of
      potent inhibitors with sultam and cyclic sulfonyl urea moieties as the P3
      capping. The bicyclic thiophene-sultam or phenyl-sultam cappings were selected
      for further SAR development. Modification at the P3 side chain determined that
      the tert-butyl group was the best choice at that position. Optimization of P1
      residue significantly improved potency and selectivity. The combination of
      optimal moieties at all positions led to the discovery of compound 33. This
      compound had the best overall profile in potency and PK profile: excellent
      K(i)(*) of 5.3 nM and activity in replicon (EC(90)) of 80 nM, extremely high
      selectivity of 6100, and a good rat PO AUC of 1.43 microMh.

PMID- 19168352
TI  - Non-urea functionality as the primary pharmacophore in soluble epoxide hydrolase
      inhibitors.
AB  - Inhibition of soluble epoxide hydrolase has been proposed as a promising new
      pharmaceutical target for diseases involving hypertension and vascular
      inflammation. The most potent sEH inhibitors reported to date contain a urea or
      amide moiety as the central or 'primary' pharmacophore. We evaluated replacing
      the urea pharmacophore with other functional groups such as thiourea,
      sulfonamide, sulfonylurea, aminomethylene amide, hydroxyamide, and ketoamide to
      identify novel and potent inhibitors. The hydroxyamide moiety was identified as a
      novel pharmacophore affording potency comparable to urea.

PMID- 19168353
TI  - Discovery and SAR of para-alkylthiophenoxyacetic acids as potent and selective
      PPARdelta agonists.
AB  - Synthesis and SAR of para-alkylthiophenoxyacetic acids is described. Achiral
      compounds 30, 31 and 32 were identified as potent and selective PPARdelta
      agonists.

PMID- 19168354
TI  - A simple in vitro assay for assessing the reactivity of nitrile containing
      compounds.
AB  - A quantitative assay involving the reaction of nitriles with glutathione and
      cysteine has been used as a simple in vitro screen to assess potential toxicity
      risk of candidate compounds in drug discovery. Studies have indicated that, when
      benchmarked with selected compounds, the reaction of the nitriles with
      glutathione can provide a useful tool for deciding whether or not to progress
      compounds in the absence of radiolabelling studies.

PMID- 19168355
TI  - 5-Aryl-4-(5-substituted-2,4-dihydroxyphenyl)-1,2,3-thiadiazoles as inhibitors of
      Hsp90 chaperone.
AB  - A series of 5-aryl-4-(5-substituted-2,4-dihydroxyphenyl)-1,2,3-thiadiazoles were
      synthesized and their binding to several constructs of human Hsp90 chaperone
      measured by isothermal titration calorimetry (ITC). The most potent compound
      bound Hsp90 with the dissociation constant of about 5 nM.

PMID- 19168356
TI  - Cell-cycle control in the face of damage--a matter of life or death.
AB  - Cells respond to DNA damage or defects in the mitotic spindle by activating
      checkpoints that arrest the cell cycle. Alternatively, damaged cells can undergo
      cell death by the process of apoptosis. The correct balance between these
      pathways is important for the maintenance of genomic integrity while preventing
      unnecessary cell death. Although the molecular mechanisms of the cell cycle and
      apoptosis have been elucidated, the links between them have not been clear.
      Recent work, however, indicates that common components directly link the
      regulation of apoptosis with cell-cycle checkpoints operating during interphase,
      whereas in mitosis, the control of apoptosis is directly coupled to the cell
      cycle machinery. These findings shed new light on how the balance between cell
      cycle progression and cell death is controlled.

PMID- 19168357
TI  - The effect of additional hand contact on postural stability perturbed by a moving
      environment.
AB  - Additional hand contact of external objects has been shown to reduce postural
      instability caused by a deficiency of one or more senses. Little is known,
      however, if additional contact can help in an environment where the senses are
      available but conflicting. This question was investigated by analyzing the effect
      of different types of hand contact on postural stability perturbed by the moving
      visual scene. While standing for 1min on a rocker board in front of a screen,
      eight healthy young subjects observed a projection of a virtual ship rocking on
      water to simulate standing on the ship's deck. In randomly assigned trials
      subjects were asked (a) to stand with arms at sides (with no contact); (b) to
      hold a standard cane parallel to the ground; (c) to lightly touch a rocker cane
      handle with their index finger; or (d) touch a standard quad cane handle with
      their index finger. Based on the kinematic data collected, the displacement of
      the center of mass (COM) and angular displacements in the hip and ankle joints
      were computed. Results showed that the moving visual scene perturbed body
      stability. However, additional contact with support of varying stability reduced
      the destabilizing effect. The results can be potentially used for practical
      purposes; when in an environment with visual perturbations simply holding an
      object in hand may help stabilize the body when at risk for a fall.

PMID- 19168358
TI  - Precision of shoulder anatomical landmark calibration by two approaches: a CAST
      like protocol and a new anatomical palpator method.
AB  - The objective of the study was to compare the precision of shoulder anatomical
      landmark palpation using a CAST-like method and a newly developed anatomical
      palpator device (called A-Palp) using the forefinger pulp directly. The repeated
      measures experimental design included four examiners that twice repeated
      measurements on eleven scapula and humerus anatomical landmarks during two
      sessions. Inter-session and inter-examiner precision was determined on
      volunteers. A-Palp accuracy was obtained from in vitro measurements and using
      virtual palpation on 3D bone models. Error propagation on the motion
      representation was also analyzed for a continuous motion of abduction movement
      performed in the shoulder joint. Palpation results showed that CAST and A-Palp
      methods lead to similar precision with the Maximal A-Palp calibration error being
      1.5mm. In vivo precision of the CAST and A-Palp methods varied between 4mm (inter
      session) and 8mm (inter-examiner). Mean propagation of the palpation error on the
      motion graph representation was 2 degrees and 5 degrees for scapula and humerus,
      respectively. A-Palp accuracy was 3.6 and 8.1mm for scapula and humerus,
      respectively. The A-Palp seems promising and could probably become an additional
      method next to today's marker-based motion analysis systems (i.e., Helen-Hayes
      configuration, CAST method).

PMID- 19168359
TI  - Effects of localized muscle fatigue on recovery from a postural perturbation
      without stepping.
AB  - Several investigations have demonstrated that localized muscle fatigue (LMF)
      causes an increase in postural sway measures during quiet stance. Since many
      falls are likely the result of a postural perturbation, this study investigated
      the effects of LMF on balance recovery from sagittal plane postural
      perturbations. Thirty-two participants (16 young, 16 older) were tested. Postural
      perturbations were administered with ballistic pendulums before and after
      exercises to fatigue the lumbar extensors and plantar flexors. Measures of
      balance recovery were based on the center of pressure (COP) and center of mass
      (COM) trajectories and the maximum perturbation that could be withstood without
      stepping. A covariate analysis that included initial conditions at the time of
      the perturbation was also performed. The results demonstrated changes in the COM
      trajectory that were consistent with an LMF-induced decrement in the ability to
      recover from the perturbations without stepping. Interpretation of the COP
      trajectory was presented in light of the COM and indicated a modified postural
      control strategy following LMF.

PMID- 19168360
TI  - A caspase homolog keeps CED-3 in check.
AB  - Apoptosis is a highly conserved form of cell death that is essential for
      controlling cell numbers throughout the lifetime of an organism. In
      Caenorhabditis elegans, the final step in the apoptotic cascade is activation of
      the death-inducing protease CED-3. Until now, no direct negative regulators of
      CED-3 had been identified, so the mechanism for maintaining a proper life-death
      balance was unclear. Now, a new study identifies CSP-3 as an important negative
      regulator of CED-3 during C. elegans development.

PMID- 19168361
TI  - Remarkable enhancement in the DNA-binding ability of C2-fluoro substituted
      pyrrolo[2,1-c][1,4]benzodiazepines and their anticancer potential.
AB  - C2-Fluoro substituted DC-81, and its dimers that comprise of two C2-fluoro
      substituted DC-81 subunits tethered to their C8-position through simple alkane
      spacers as well as piperazine moiety side-armed with symmetrical alkyloxy spacers
      have been designed and synthesized. These fluoro substituted pyrrolo[2,1
      c][1,4]benzodiazepines have shown remarkable DNA-binding ability and most of them
      possess promising anticancer activity, having GI(50) values in micromolar to
      nanomolar concentration range. DNA thermal denaturation studies show that some of
      these compounds (14a-c and 15) increase the DeltaT(m) values in the range of 28.9
      38 degrees C, and this is further confirmed by the restriction endonuclease
      studies. This study illustrates the importance of introducing fluoro substitution
      at the C2-position apart from the incorporation of a piperazine ring in between
      the alkyloxy linker for enhancement of the DNA-binding ability in comparison to
      DSB-120 and SJG-136 (DeltaT(m)=10.2 and 25.7 degrees C). Moreover, the variations
      in the DNA-binding ability with respect to fluoro substitution in this class of
      dimers has been investigated by molecular modeling studies. Some representative
      C2-fluoro substituted dimers (8a and 14a) have also exhibited significant
      anticancer activity in the 60 cancer cell line assay of the National Cancer
      Institute (NCI).

PMID- 19168362
TI  - Synthesis of new analogs of benzotriazole, benzimidazole and phthalimide-
      potential inhibitors of human protein kinase CK2.
AB  - New derivatives of 4,5,6,7-tetrabromo-1H-1,2,3-benzotriazole (TBBt), 4,5,6,7
      tetrabromo-1H-benzimidazole (TBBi), and N-substituted tetrabromophthalimides were
      synthesized and their effect on the activity of human protein kinase CK2 was
      examined. The most active were derivatives with N-hydroxypropyl substituents
      (IC(50) in 0.32-0.54 microM range) whereas derivatives of phthalimide were almost
      ineffective.

PMID- 19168363
TI  - New potent imidazoisoquinolinone derivatives as anti-Trypanosoma cruzi agents:
      biological evaluation and structure-activity relationships.
AB  - A series of novel benzoimidazo and N-aryl-5-oxo-imidazo[1,2-b]isoquinoline-10
      carbothioamides was developed. All the compounds were evaluated for their in
      vitro action against the epimastigote form of Trypanosoma cruzi. Four of them
      showed higher activity than Nifurtimox. Their unspecific cytotoxicity was
      evaluated using HeLa and L6 cells, being non-toxic at concentrations at least 15
      and 200 times higher than that of T. cruzi IC(50.) To gain insight into the
      mechanism of action, their DNA binding properties and reactivity with glutathione
      were studied, and QSAR study was performed.

PMID- 19168364
TI  - New ventures in the chemistry of avermectins.
AB  - An overview is given on recent work towards new avermectin derivatives of
      extremely high insecticidal and acaricidal activity. These compounds were
      prepared from commercially available abamectin (avermectin B1) 1. For the
      synthesis, many novel entries have been opened up, making use of modern synthetic
      methods and applying them, for the first time, to the chemistry of avermectins.
      Several types of avermectin derivatives can be regarded as key innovations in the
      field. These are, in particular, 4''-deoxy-4''-(S)-amino avermectins 3, 4'-O
      alkoxyalkyl avermectin monosaccharides 5, 4''-deoxy-4''-C-substituted 4''-amino
      avermectins 6 and 2''-substituted avermectins 7. 4''-Deoxy-4''-(S)-amino
      avermectins 3 were obtained by the consecutive application of the Staudinger and
      Aza-Wittig reaction. 4'-O-Alkoxyalkyl avermectin monosaccharides 5 were prepared
      by alkoxyalkylation of 5-O-protected avermectin monosaccharide. For the synthesis
      of 4''-deoxy-4''-C-substituted 4''-amino avermectins 6, several methods were used
      to construct the fully substituted 4''-carbon centre, such as a modified Strecker
      synthesis, the addition of organometallics to a 4''-sulfinimine and a modified
      Ugi approach. In order to prepare 2''-substituted avermectins 7, 5-O-protected
      avermectin monosaccharide was coupled with carbohydrate building blocks. An
      alternative synthesis involved the hitherto unknown enol ether chemistry of 4''
      oxo-avermectin and the conjugate addition of a cuprate to an avermectin 2'',3''
      en-4''-one. In addition, a number of other highly potent derivatives were
      synthesised. Examples are 4''-O-amino avermectins 8, as well as products arising
      from intramolecular rhodium catalysed amidations and carbene insertions. A
      radical cyclisation led to an intriguing rearrangement of the avermectin
      skeleton. Many of the new avermectins surpassed the activity of abamectin 1
      against insects and mites.

PMID- 19168365
TI  - Protein structure based rational design of ecdysone agonists.
AB  - We review the impact of protein X-ray crystallography on the rational design of
      insecticides that act as agonists of the ligand-binding domain of the Ecdysone
      receptor (EcR). As the EcR is a target specific to insects, these compounds
      potentially constitute new chemical classes of safe insecticides. The increased
      insight relative to that from ligand-only based (Quantitative) Structure-Activity
      Relations (QSARs), classical 2D-Hansch type or 3D-CoMFA/CoMSIA (Comparative
      Molecular Field/Similarity Analysis), is discussed. The importance of protein X
      ray structure determination in support of the discovery process is stressed as
      the simplistic lock-and-key picture fails due to the remarkable flexibility of
      the EcR ligand binding site. Several new non-steroidal chemical classes of
      ecdysone agonists, designed by guidance from protein X-ray studies, are
      described.

PMID- 19168366
TI  - A simple, versatile, low-cost and remotely operated apparatus for [11C]acetate,
      [11C]choline, [11C]methionine and [11C]PIB synthesis.
AB  - A simple, efficient and remotely operated synthesis apparatus for carrying out
      routine [(11)C]carboxylation, on-column and bubbling [(11)C]methylation was
      essential for reliable, day-to-day production of [(11)C]-labelled PET
      radiopharmaceuticals. We developed an in-house apparatus specifically applied to
      the synthesis of [(11)C]acetate, [(11)C]choline, [(11)C]methionine and 2-(4'-N
      [(11)C]methylaminophenyl)-6-hydroxybenzothiazole ([(11)C]PIB), where high
      radiochemical purity (>or= 97%) and moderate radiochemical yields (18% for
      [(11)C]PIB, 41-55% for the others) could be achieved. These findings provided
      evidence that this was a fast, versatile and reliable apparatus suitable for a
      PET/CT centre with limited financial budget and hot cell space for synthesis of
      [(11)C]-labelled radiopharmaceuticals.

PMID- 19168367
TI  - Distribution of naturally occurring radionuclides activity concentration in East
      Malaysian marine sediment.
AB  - Studies of naturally occurring radioactive materials (NORM) distribution of
      (226)Ra, (228)Ra and (40)K in East Malaysia were carried out as part of a marine
      coastal environment project. The results of measurements will serve as baseline
      data and background reference level for Malaysia coastlines. Sediments from 21
      coastal locations and 10 near shore locations were collected for analyses. The
      samples were dried, finely ground, sealed in a container and stored for a minimum
      of 30 days to establish secular equilibrium between (226)Ra and (228)Ra and their
      respective radioactive progenies. They were counted using a high-purity germanium
      (HPGe) spectrometer covering the respective progeny energy peak. For (40)K, the
      presence of this was measured directly via its 1460 keV energy peak. The
      concentration of (226)Ra, (228)Ra and (40)K in samples obtained from coastal
      Sarawak ranged between 23 and 41 (mean 30+/-2) Bq/kg, 27 and 45 (mean 39+/-4)
      Bq/kg and 142 and 680 (mean 462+/-59) Bq/kg, respectively. Meanwhile, the
      concentration of (226)Ra, (228)Ra and (40)K for samples obtained from coastal
      Sabah ranged between 16 and 30 (mean 23+/-2) Bq/kg, 23 and 45 (mean 35+/-4) Bq/kg
      and 402 and 842 (mean 577+/-75) Bq/kg, respectively. For the Sarawak near shore
      stations, the concentration of (226)Ra, (228)Ra and (40)K ranged between 11 and
      36 (mean 22+/-2) Bq/kg, 21 and 65 (mean 39+/-5) Bq/kg and 149 and 517 (mean 309+/
      41) Bq/kg, respectively. Meanwhile, the concentration of (226)Ra, (228)Ra and
      (40)K for samples obtained from Sabah ranged between 9 and 31 (mean 14+/-2)
      Bq/kg, 10 and 48 (mean 21+/-3) Bq/kg and 140 and 580 (mean 269+/-36) Bq/kg,
      respectively. The calculated external hazard values of between 0.17 and 0.33
      (less than unity) showed that there is little risk of external hazard to the
      workers handling the sediments.

PMID- 19168368
TI  - Qualitative values of radioactivity, area and volumetric: application on phantoms
      (target and background).
AB  - The visualization of a lesion depends on the contrast between the lesion and
      surrounding background (T/B; (target/background) ratio). For imaging in vivo not
      only is the radioactivity in the target organ important, but so too is the ratio
      of radioactivity in the target versus that in the background. Nearly all studies
      reported in the literature have dealt with the surface index, as a standard
      factor to study the relationship between the target (tissue or organ) and the
      background. It is necessary to know the ratio between the volumetric activity of
      lesions (targets) and normal tissues (background) instead of knowing the ratio
      between the area activity, the volume index being a more realistic factor than
      the area index as the targets (tissues or organs) are real volumes that have
      surfaces. The intention is that this work should aid in approaching a
      quantitative relationship and differentiation between different tissues
      (target/background or abnormal/normal tissues). For the background, square
      regions of interest (Rios) (11 x 11 pixels in size) were manually drawn by the
      observer at locations far from the border of the plastic cylinder (simulated
      organ), while an isocontour region with 50% threshold was drawn automatically
      over the cylinder. The total number of counts and pixels in each of these regions
      was calculated. The relationship between different phantom parameters, cylinder
      (target) depth, area activity ratio (background/target, A(B/T)) and real
      volumetric activity ratio (background/target, V(B/T)), was demonstrated.
      Variations in the area and volumetric activity ratio values with respect to the
      depth were deduced. To find a realistic value of the ratio, calibration charts
      have been constructed that relate the area and real volumetric ratios as a
      function of depth of the tissues and organs. Our experiments show that the cross
      sectional area of the cylinder (applying a threshold 50% isocontour) has a weak
      dependence on the activity concentrations of the background.

PMID- 19168369
TI  - Spatial and spectral characteristics of a compact system neutron beam designed
      for BNCT facility.
AB  - The development of suitable neutron sources and neutron beam is critical to the
      success of Boron Neutron Capture Therapy (BNCT). In this work a compact system
      designed for BNCT is presented. The system consists of (252)Cf fission neutron
      source and a moderator/reflector/filter/shield assembly. The
      moderator/reflector/filter arrangement has been optimized to maximize the
      epithermal neutron component which is useful for BNCT treatment of deep seated
      tumors with the suitably low level of beam contamination. The MCMP5 code has been
      used to calculate the different components of neutrons, secondary gamma rays
      originating from (252)Cf source and the primary gamma rays emitted directly by
      this source at the exit face of the compact system. The fluence rate
      distributions of such particles were also computed along the central axis of a
      human head phantom.

PMID- 19168370
TI  - Surgeons produce innovative ideas which are frequently lost in the labyrinth of
      patents.
AB  - Thoracic and cardiovascular surgery are innovative specialties that regularly
      recruit the latest technological developments into their armoury of devices and
      equipment. The introduction of new technology is dependant on patents; an
      important but single component of intellectual property. Patents enable the
      attribution of rights to concepts, ideas and inventions and this facilitates
      ownership, subsequent licensing and overall management of innovation and its
      outcome. It is not just thoracic and cardiovascular surgery, but the healthcare
      world in general that experiences ongoing technological evolution; so to remain
      contemporary, it is important that those in positions of responsibility are
      familiar with the relevant processes. This requires basic medico-legal knowledge
      and may be entwined with significant financial responsibility. Penetrating
      clinical, academic and industrial environments, informed awareness of patents
      also contributes to important leadership skills, encouraging the incorporation of
      innovation into the professional milieu. We aim to present through this
      manuscript an overview of these issues in order to promote awareness of patents
      within thoracic and cardiovascular surgery using a descriptive and practical
      approach.

PMID- 19168371
TI  - The cytotoxicity of self-etching primer bonding agents in vitro.
AB  - OBJECTIVE: This study evaluated the cytotoxicity of 3 self-etching bonding
      systems: Optibond Solo Plus SE primer, Xeno III, and i Bond. STUDY DESIGN: The
      test materials were applied on the dentine discs of dentine barrier models in the
      same way as in the clinical procedures recommended by each manufacturer. 3-D cell
      culture of Bovine pulp-derived cells transfected with Simian virus 40 Large T
      antigen and perfusion condition were conducted in this experiment. Cell viability
      after exposure to the bonding agents was determined by
      dimethylthiazolediphenyltetrazolium bromide (MTT) assay. RESULTS: The results
      revealed that cell survival with the above-mentioned bonding agents was 99.66%,
      72.59%, and 10.65%, respectively. i Bond is the most toxic material (P < .05).
      Xeno III is less toxic than i Bond but more toxic than Optibond Solo Plus SE
      primer (P < .05). CONCLUSIONS: Among the 3 test self-etching bonding systems,
      Optibond Solo Plus SE primer should be selected in cases where the remaining
      dentin above pulp tissue is 0.5 mm or less.

PMID- 19168372
TI  - What is the adequate margin of surgical resection in oral cancer?
AB  - OBJECTIVE: The "adequate surgical margin" has always remained an enigma in the
      minds of head and neck surgeons. This study systematically analyses the impact of
      the width of the clear surgical margin on survival in oral cancer. STUDY DESIGN:
      A historical cohort of 277 surgically treated patients with oral cancer were
      followed for a median period of 36 months. Cox proportional hazard models were
      used to determine the independent effect of the clear surgical margin, in
      millimeters, on 5-year survival. RESULTS: Patients with margins of 5 mm or more
      had a 5-year survival rate of 73% when compared to those with margins of 3 to 4
      mm (69%) , 2 mm or less (62%), and involved margins (39%, P = .000). After
      controlling for confounding variables (age, gender, stage) each 1-mm increase in
      clear surgical margin decreased the risk of death at 5 years by 8% (HR 0.92; 95%
      CI 0.86, 0.99; P = .021). Based on this model, patients with positive surgical
      margins had a 2.5-fold increase in risk of death at 5 years and those with close
      (<or= 3 mm) margins had a 1.5-fold increase in risk of death (P = 0.076) when
      compared to patients with margins greater than 3 mm (P = .000). CONCLUSIONS:
      Survival improves with each additional millimeter of clear surgical margin. This
      systematic evaluation of surgical margins suggests that an adequate resection in
      oral cancer should provide a margin of greater than 3 mm on permanent pathology
      section.

PMID- 19168373
TI  - Accuracy of electronic apex locater-controlled handpieces.
AB  - An in vitro model was used to test a hypothesis that the manual (apex locator)
      and motor-driven (apex locator-controlled handpiece) operating modes of 3 newly
      developed apex-locator-controlled handpiece devices (Dentaport ZX, Endomaster,
      XSmart Dual) give the same working length. The depth of penetration of the file
      into the root canal was measured using a digital micrometer and the distance of
      the tip of the file relative to the major root foramen was determined by scanning
      electron microscopy (SEM). In the manual mode, the XSmart Dual device reported
      significantly shorter working lengths than the Dentaport ZX or the Endomaster
      devices. In the motor-driven mode, the XSmart Dual device reported significantly
      longer working lengths than the Dentaport ZX but not the Endomaster. Most
      instruments driven by the handpieces were confined within the root canal and
      differences in working lengths between manual and motor-driven modes were small
      for all devices (tenths of millimeters). We concluded that although the motor
      driven mode of these devices appeared to be clinically safe, measurements
      obtained in manual and motor-driven operating modes are not equivalent.

PMID- 19168374
TI  - Nonsurgical endodontic treatment of Type III dens invaginatus in maxillary
      canine: an 18-month follow-up.
AB  - Dens invaginatus (DI) is a developmental variation resulting from an infolding of
      the outer enamel surface of a tooth into the interior. The greatest difficulty in
      the endodontic treatment of DI is in locating the rudimentary root canal, because
      of the atypical internal morphologic complexity. Invagination may also restrict
      sufficient cleaning and shaping. This case report describes a nonsurgical root
      canal treatment of Type 3 DI in a maxillary canine. Despite the complex anatomy
      of dens invaginatus, nonsurgical endodontic treatment was performed successfully
      and at follow-up examination after 18 month, healing was achieved without any
      need for further surgical intervention.

PMID- 19168375
TI  - Successful treatment of a radicular groove by intentional replantation and
      Emdogain therapy: four years follow-up.
AB  - Radicular groove is an anatomical malformation that often causes severe
      periodontal defects. Treatments of such an anomaly present a clinical challenge
      to the operator. Presented is a case of successful treatment of radicular groove
      associated with a maxillary lateral incisor of a 15-year-old girl. A combination
      of endodontics, intentional replantation, and Emdogain therapy was used. At 4
      year follow-up, the patient was comfortable and complete resolution of the
      periapical pathology was evident.

PMID- 19168376
TI  - Overfilling of calcium hydroxide-based paste Calcipex II produced a foreign body
      granuloma without acute inflammatory reaction.
AB  - A patient, a 62-year-old man, received endodontic treatment of the lower left
      canine complicated by apical overfilling of Calcipex II. At the second day after
      the root canal filling, the 14th day after placement of Calcipex II intracanal
      medication, he complained of a gingival swelling in the treated area. The
      incisional biopsy of the gingival swelling revealed a foreign body granuloma
      infiltrated with macrophages engulfing the fine Calcipex II granules but with
      polymorphonuclear leukocytes (PMNs). However, the gingival swelling was healed
      uneventfully, and the tooth was free of symptoms at 4 months' follow-up. This
      study first reports the Calcipex II-induced reaction in human periodontium. In
      the immunohistochemistry using antisera of lysozyme, CD31, CD68, interleukin-8
      (IL-8), and poly(ADP-ribose) polymerase 1 (PARP-1), the granule-laden cells are
      positive for lysozyme, CD31, CD68, and PARP-1, but negative for IL-8. Thus, it is
      presumed that the granule-laden cells belong to the macrophages/monocytes rather
      than the PMNs, and that they gradually undergo the apoptotic processes. These
      data suggest that the canal dressing material, Calcipex II, is able to be widely
      dispersed into the periodontal tissues, primarily engulfed by macrophages, and
      resulted in the foreign body granuloma in the absence of acute inflammatory
      reaction.

PMID- 19168377
TI  - Mineralization density and apparent density in mandibular condyle bone.
AB  - OBJECTIVES: This study evaluated a method for determining the density and
      distribution of bone of mandibular condyles using proprietary computerized
      tomography (CT) software. STUDY DESIGN: Thirty-eight condylar specimens were
      investigated with a high-resolution multislice CT. The density was determined by
      using bone density analysis algorithms available within the proprietary software.
      Apparent density was estimated over the total cross-sectional area, the total
      trabecular bone area apart from the cortical fraction, and on individually
      selected points. Color-coded pictures were created to demonstrate density
      differences. RESULTS: The cortical bone presented significantly higher densities
      than the trabecular bone. The anterior cortical bone had significantly higher
      densities than the posterior. The central anterior cortical and the central
      trabecular areas showed significantly higher densities than the medial and
      lateral areas. CONCLUSION: This technique proved to be a valuable method for
      determination of the differences in density in the mandibular condyle. It shows
      potential in providing clinicians with an imaging modality for specific clinical
      use.

PMID- 19168378
TI  - Comparison of radiation dose for implant imaging using conventional spiral
      tomography, computed tomography, and cone-beam computed tomography.
AB  - OBJECTIVE: The objective of this study was to compare typical patient radiation
      dose delivered in implant imaging with spiral computed tomography (CT),
      conventional spiral tomography, and cone-beam CT (CBCT). STUDY DESIGN: The
      Scanora (Orion Corporation Soredex, Helsinki, Finland), Spiral HiSpeed/Fxi
      (General Electric, Milwaukee, WI), and Classic iCAT (Imaging Sciences
      International, Hatfield, PA) units were selected to represent conventional spiral
      tomography, spiral CT, and CBCT, respectively. Thermoluminescent dosimeters were
      used in a Rando phantom to measure radiation-absorbed doses to the lenses,
      parotid glands, submandibular glands, sublingual gland, and the thyroid for
      maxillary and mandibular implant imaging techniques. RESULTS: Spiral CT delivered
      the highest absorbed dose, whereas CBCT delivered the lowest in both maxillary
      and mandibular implant scans. The salivary glands received the highest absorbed
      doses. Scanora delivered lower radiation doses than CBCT when the anterior region
      of the maxilla or mandible was irradiated. CONCLUSION: In implant imaging, CT
      delivers the highest radiation dose to the salivary glands, whereas the CBCT
      system studied delivers the lowest dose. Irrespective of imaging modality, during
      implant imaging as conducted for this study, salivary glands receive most
      radiation.

PMID- 19168379
TI  - Recurrent double lip: literature review and report of a case.
AB  - Double lip is a rare oral anomaly caused by hyperplastic tissue of the labial
      mucosa that becomes more prominent with tension caused by smiling. This
      congenital or acquired abnormality can interfere with chewing, speaking, and
      esthetics. Recognition of double lip and appropriate surgical treatment can
      reduce these potential problems. The purpose of this article is to review the
      literature regarding double lip and present an unusual case of recurrence
      simultaneously involving the upper and lower lips.

PMID- 19168380
TI  - Sleep continuity and architecture: associations with pain-inhibitory processes in
      patients with temporomandibular joint disorder.
AB  - Recent research suggests bi-directional interactions between the experience of
      pain and the process of sleep; pain interferes with the ability to obtain sleep,
      and disrupted sleep contributes to enhanced pain perception. Our group recently
      reported, in a controlled experimental study, that sleep fragmentation among
      healthy adults resulted in subsequent decrements in endogenous pain inhibition.
      The present report follows up that observation by extending this line of research
      to a sample of patients experiencing persistent pain. Patients with chronic
      temporomandibular joint disorder (TMD) pain were studied using polysomnography
      and psychophysical evaluation of pain responses. We assessed whether individual
      differences in sleep continuity and/or architecture were related to diffuse
      noxious inhibitory controls (DNIC), a measure of central nervous system pain
      inhibition. Among 53 TMD patients, higher sleep efficiency and longer total sleep
      time were positively associated with better functioning of DNIC (r=0.42-0.44,
      p<0.01; ps<0.05 for the multivariate analyses). These results suggest the
      possibility that disrupted sleep may serve as a risk factor for inadequate pain
      inhibitory processing and hint that aggressive efforts to treat sleep disturbance
      early in the course of a pain condition might be beneficial in reducing the
      severity or impact of clinical pain.

PMID- 19168381
TI  - Comparison of computational approaches for predicting the effects of missense
      mutations on p53 function.
AB  - We applied our recently developed kinetic computational mutagenesis (KCM)
      approach [L.T. Chong, W.C. Swope, J.W. Pitera, V.S. Pande, Kinetic computational
      alanine scanning: application to p53 oligomerization, J. Mol. Biol. 357 (3)
      (2006) 1039-1049] along with the MM-GBSA approach [J. Srinivasan, T.E. Cheatham
      3rd, P. Cieplak, P.A. Kollman, D.A. Case, Continuum solvent studies of the
      stability of DNA, RNA, and phosphoramidate-DNA helices, J. Am. Chem. Soc. 120
      (37) (1998) 9401-9409; P.A. Kollman, I. Massova, C.M. Reyes, B. Kuhn, S. Huo,
      L.T. Chong, M. Lee, T. Lee, Y. Duan, W. Wang, O. Donini, P. Cieplak, J.
      Srinivasan, D.A. Case, T.E. Cheatham 3rd., Calculating structures and free
      energies of complex molecules: combining molecular mechanics and continuum
      models, Acc. Chem. Res. 33 (12) (2000) 889-897] to evaluate the effects of all
      possible missense mutations on dimerization of the oligomerization domain
      (residues 326-355) of tumor suppressor p53. The true positive and true negative
      rates for KCM are comparable (within 5%) to those of MM-GBSA, although MM-GBSA is
      much less computationally intensive when it is applied to a single energy
      minimized configuration per mutant dimer. The potential advantage of KCM is that
      it can be used to directly examine the kinetic effects of mutations.

PMID- 19168382
TI  - Perioperative administration of vedaprofen, tramadol or their combination does
      not interfere with platelet aggregation, bleeding time and biochemical variables
      in cats.
AB  - A randomized double blind and placebo controlled design was used to investigate
      the hemostatic, biochemical, gastrointestinal and behavioral effects of pre- and
      postoperative administration of vedaprofen 0.5mg/kg PO (V), tramadol 2mg/kg SC
      (T), their association (VT) or placebo (P) in 40 adult female cats (3.0+/-0.32kg;
      1.8+/-0.7 years) distributed in groups of 10. Platelet aggregation and bleeding
      time were measured before and 52h after ovariohysterectomy. Serum urea,
      creatinine, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl
      transferase concentrations were measured before and 7 days postoperatively. The
      occurrence of vomiting, frequency and consistency of feces, and behavior were
      observed for 7 days postoperatively. Morphine (0.5mg/kg, IM) was used as rescue
      analgesic. Laboratory variables did not change. Vomiting was observed only after
      morphine administration. Mild euphoria was observed in T and VT. The
      perioperative use of vedaprofen and/or tramadol did not modify the hemostatic,
      biochemical and gastrointestinal function in cats.

PMID- 19168383
TI  - Exploring the evolution of (1,3;1,4)-beta-D-glucans in plant cell walls:
      comparative genomics can help!
AB  - A key distinguishing feature of the grasses is that their cell walls contain
      (1,3;1,4)-beta-D-glucans, which are distributed almost exclusively within the
      Poaceae. The identification of genes that mediate in (1,3;1,4)-beta-D-glucan
      biosynthesis has been possible through relatively recent genome sequencing
      programmes and comparative genomics techniques. The evolution of a single new
      gene appears to have been sufficient for the first synthesis of (1,3;1,4)-beta-D
      glucans and there is compelling evidence that existing hydrolytic enzymes were
      adapted for the specific hydrolysis of the polysaccharide during wall turnover or
      degradation. Manipulation of the expression levels of genes involved in (1,3;1,4)
      beta-D-glucan synthesis is likely to provide opportunities to enhance the value
      of grasses and cereals in commercial applications such as human nutrition and
      biofuel production.

PMID- 19168384
TI  - Pseudomonas syringae type III secretion system effectors: repertoires in search
      of functions.
AB  - The ability of Pseudomonas syringae to grow and cause diseases in plants is
      dependent on the injection of multiple effector proteins into plant cells via the
      type III secretion system (T3SS). Genome-enabled bioinformatic/experimental
      methods have comprehensively identified the repertoires of effectors and related
      T3SS substrates for P. syringae pv. tomato DC3000 and three other sequenced
      strains. The effector repertoires are diverse and internally redundant. Insights
      into effector functions are being gained through the construction of mutants
      lacking one or more effector genes, which may be reduced in growth in planta, and
      through gain-of-function assays for the ability of single effectors to suppress
      plant innate immune defenses, manipulate hormone signaling, elicit cell death,
      and/or display biochemical activities on plant protein targets.

PMID- 19168385
TI  - Role of Pseudomonas aeruginosa type III effectors in disease.
AB  - Pseudomonas aeruginosa uses a type III secretion system (T3SS) to directly inject
      four known effectors into host cells. ExoU is a potent cytotoxin with
      phospholipase A2 activity that causes rapid necrotic death in many cell types.
      The biological function of ExoY, an adenylate cyclase, remains incompletely
      defined. ExoS and ExoT are closely related bifunctional proteins with N-terminal
      GTPase activating protein (GAP) activity toward Rho family proteins and C
      terminal ADP ribosylase (ADPRT) activity toward distinct and non-overlapping set
      of targets. While almost no strain encodes or secretes all four effectors, the
      commonly found combinations of ExoU/ExoT or ExoS/ExoT provides redundant and
      failsafe mechanisms to cause mucosal barrier injury, inhibit many arms of the
      innate immune response, and prevent wound repair.

PMID- 19168386
TI  - How Xanthomonas type III effectors manipulate the host plant.
AB  - Pathogenicity of Xanthomonas and most other Gram-negative phytopathogenic
      bacteria depends on a conserved type III secretion (T3S) system which injects
      more than 25 different effector proteins into the plant cell. Extensive studies
      in the last years on the molecular mechanisms of type III effector function
      revealed that effector proteins with enzymatic functions seem to play important
      roles in the interaction of Xanthomonas with its host plants, for example, the
      SUMO protease XopD. In addition, xanthomonads express a unique class of type III
      effectors to pursue another strategy. Effectors of the AvrBs3 family, so far only
      identified in Xanthomonas spp. and Ralstonia solanacearum, mimic plant
      transcriptional activators and manipulate the plant transcriptome.

PMID- 19168387
TI  - Enzymatic determination of vitamin A in pharmaceutical formulations with
      spectrophotometric detection.
AB  - An enzymatic method for the determination vitamin A (retinol) is reported using
      soluble and immobilized alcohol dehydrogenase, isolated from rabbit liver. The
      reaction is based on the oxidation of retinol and simultaneous reduction of
      NAD(+) to NADH followed by spectrophotometric detection at 340 nm. The
      calibration graph was linear over the range of 2.0-10 microM with correlation
      coefficients of 0.9967 and 0.9992 (n=5) for soluble and immobilized alcohol
      dehydrogenase respectively, with relative standard deviations (n=3) in the range
      of 0.5-1.2%. The limit of detection was lower than 1.0 microM. The proposed
      method was applied to determine vitamin A in pharmaceuticals, and the results
      obtained were in reasonable agreement with the amount labeled. The results were
      compared using spectrophotometric reference method, and no significant difference
      was found between the results of the both methods.

PMID- 19168388
TI  - Identification of two Hepatitis C Virus isolates that failed genotyping by
      Versant LiPA 2.0 assay.

PMID- 19168389
TI  - Nine-year trends in clinically relevant reduced susceptibility of HIV-1 to
      antiretrovirals.
AB  - BACKGROUND: Temporal changes in HIV-1 resistance both reflect and influence the
      clinical use of antiretrovirals (ARVs). OBJECTIVE: To determine temporal trends
      in reduced susceptibility to ARVs and resistance mutations in routine clinical
      samples (RCS) from HIV infected patients. STUDY DESIGN: Calculated fold-changes
      (FC) for ARVs were determined for viral genotypes from RCS received between July
      1998 and June 2007 using vircoTYPE HIV-1 (Version 4.2.01). The prevalence of
      isolates with clinically relevant reduced susceptibility and of resistance
      mutations were determined for consecutive 6-month periods. RESULTS: 242,003 RCS
      were identified. The prevalence of RCS exhibiting reduced susceptibility to > or
      =1 drug among any of three ARV classes decreased from 82% to 66.5% and of these,
      to > or =1 drug in each of the three ARV classes and from 30.5% to 15.7% from
      December 98 to June 07 (p< or =0.0001). The prevalence of mutations associated
      with NRTI, NNRTI and PI resistance generally reflected evolving use of these drug
      classes. Among fully susceptible RCS, isolates that exhibited resistance
      mutations were rare. CONCLUSIONS: Clinically relevant reduced susceptibility to
      ARVs declined over the 9-year period. There was a general higher prevalence of
      reduced susceptibility to RT inhibitors than to PIs.

PMID- 19168390
TI  - Sleep-disordered breathing: impact on functional outcome of ischemic stroke
      patients.
AB  - BACKGROUND AND PURPOSE: Sleep-disordered breathing (SDB) is more prevalent in
      stroke patients than age- and sex-matched controls, but the relationship between
      SDB and functional outcome of stroke patients is unclear. The aim of our study
      was to determine the prevalence of SDB in ischemic stroke and its influence on
      functional outcome at 3 and 6 months after stroke onset. METHODS: In a
      prospective study, 60 patients were selected by polysomnography (PSG). The apnea
      hypopnea index (AHI) was determined 6.5+/-3.2 days after stroke onset. Neurologic
      severity at admission was assessed by the Scandinavian Stroke Scale (SSS) and
      outcome by the Barthel Index (BI). Patients were evaluated on admission, 3 and 6
      months after stroke onset. RESULTS: Among the 60 patients, 39 (65%) patients had
      SDB (AHI5); of these, 30 patients (50%) had AHI15 and 18 (30%)>30. On Logistic
      regression analysis, the BI at 3 months was independently predicted by SSS
      (OR=0.74, 95% CI [0.62-0.88], P=0.001) and AHI (OR=1.09, 95% CI [1.02-1.17],
      P<0.05). At 6 months, the BI was predicted only by SSS (OR=0.83, 95% CI [0.74
      0.92], P=0.001). CONCLUSIONS: SDB is common in patients during acute phase after
      stroke onset. SDB appears to be associated with a worse functional outcome during
      the early recovery period following stroke, increasing the likelihood of
      dependency.

PMID- 19168391
TI  - Malaria treatment: no place like home.
AB  - If the United Nations Millennium Development Goals are to be met, there is a need
      to improve access to effective antimalarial treatment where the burden of malaria
      is highest. Health facilities are often bypassed by communities, and
      inappropriate and poor-quality self-medication is common. The home management of
      malaria (HMM) strategy has been shown to have an effect on malaria morbidity and
      mortality in the chloroquine era, but several evidence gaps remain to be filled
      to confirm its value in the era of artemisinin-based combination therapies.
      Nevertheless, if a substantial reduction of the malaria burden is to be achieved,
      access to effective medicines has to be vastly improved, and in most of sub
      Saharan Africa, this will have to be through HMM.

PMID- 19168392
TI  - Malaria vector control: current and future strategies.
AB  - The recently announced call for malaria eradication represents a new page in the
      history of this disease. This has been triggered by remarkable reductions in
      malaria resulting from combined application of effective drugs and vector
      control. However, this strategy is threatened by development of insecticide
      resistance. Efforts to develop alternative tools to complement or even replace
      insecticide-based vector-control strategies must continue. Here, an overview is
      presented of the novel vector-control tools expected to contribute to malaria
      eradication.

PMID- 19168393
TI  - Urinary schistosomiasis-associated morbidity in schoolchildren detected with
      urine albumin-to-creatinine ratio (UACR) reagent strips.
AB  - OBJECTIVE: To evaluate urine albumin-to-creatinine ratio (UACR) reagent strips
      for detection of urinary tract pathology (UTP) associated with urinary
      schistosomiasis in schoolchildren from Zanzibar. PATIENTS AND METHODS: Sixty-six
      schoolchildren were examined for urinary schistosomiasis and UTP using urine
      reagent strips (Hemastix, urine microscopy and portable ultrasonography. The UACR
      was estimated using Microalbustix; univariate and logistic regression methods
      were used to test for statistical associations. RESULTS: Prevalence of egg-patent
      schistosomiasis was 65.2% while 77.3% had micro-haematuria and 66.1% had a least
      one ultrasound-identified UTP. Abnormal UACR (> or =3.4 mg/mmol) was frequent
      (88.4%) but an unsatisfactory identifier of UTP, albeit highly sensitive:
      sensitivity (SS) = 100.0%, specificity (SP) = 23.8%, positive predictive value
      (PPV) = 71.9%, negative predictive value (NPV) = 100.0%. When only severely
      abnormal UACR was considered (> or =33.9 mg/mmol), SS decreased while SP
      improved: SS = 58.5%, SP = 61.9%, PPV = 75.0%, NPV = 43.3%. CONCLUSION: Abnormal
      and severely abnormal UACRs were strongly associated with egg-patent urinary
      schistosomiasis and UTP, although via different mechanisms: respectively, from
      venous blood released directly into the urine from bladder wall perforations, and
      from leaching sera released from chronic egg-induced lesions throughout the
      urinary tract. From a control perspective, Microalbustix reagent strips are
      therefore best applied in pre-screening protocols allowing selection, or rather
      confident exclusion, of schoolchildren with urinary schistosomiasis for more
      detailed investigations.

PMID- 19168394
TI  - Contraception in historical and global perspective.
AB  - This chapter describes the rise in contraceptive practice and fall in fertility
      from around 1880 to the present day. Two main phases are identified: the first
      confined to European populations and involving methods of low efficacy, and the
      second embracing the whole planet involving modern methods. Today, sub-Saharan
      Africa is the only region where low levels of contraceptive use and high
      fertility persist. Nevertheless, nearly half of pregnancies worldwide are still
      unintended, and much scope remains for improvement in contraceptive protection.
      The main international priority is Africa, where demographic factors jeopardize
      the goals of reducing poverty and hunger.

PMID- 19168395
TI  - Explaining the clinical manifestations of T wave alternans in patients at risk
      for sudden cardiac death.
AB  - The mechanisms underlying sudden cardiac death (SCD) are complex and diverse.
      Therefore, correct application of any marker to risk stratify patients for
      appropriate therapy requires knowledge regarding how the marker is reflective of
      a particular electroanatomical substrate for arrhythmias. Noninvasive measurement
      of beat-to-beat alternation of the electrocardiographic T-wave, referred to as T
      wave alternans (TWA), is an important marker of risk for SCD. Is this
      relationship a mere association, or is TWA mechanistically linked to SCD? Recent
      experimental evidence strongly supports a mechanistic relationship between TWA
      and SCD. This review considers the underlying mechanisms of TWA derived from
      experimental studies, as they relate to clinical observations of TWA in humans,
      addressing the following questions derived from common clinical observations: (1)
      Where does TWA on the surface electrocardiogram come from? (2) Why is controlled
      heart rate elevation required to elicit TWA? (3) Why is TWA associated with risk
      for SCD? (4) Why is TWA associated with a broad range of ventricular arrhythmias?
      (5) How do commonly used medications affect TWA?

PMID- 19168396
TI  - Evidence regarding clinical use of microvolt T-wave alternans.
AB  - BACKGROUND: Microvolt T-wave alternans (MTWA) testing in many studies has proven
      to be a highly accurate predictor of ventricular tachyarrhythmic events (VTEs) in
      patients with risk factors for sudden cardiac death (SCD) but without a prior
      history of sustained VTEs (primary prevention patients). In some recent studies
      involving primary prevention patients with prophylactically implanted
      cardioverter-defibrillators (ICDs), MTWA has not performed as well. OBJECTIVE:
      This study examined the hypothesis that MTWA is an accurate predictor of VTEs in
      primary prevention patients without implanted ICDs, but not of appropriate ICD
      therapy in such patients with implanted ICDs. METHODS: This study identified
      prospective clinical trials evaluating MTWA measured using the spectral analytic
      method in primary prevention populations and analyzed studies in which: (1) few
      patients had implanted ICDs and as a result none or a small fraction (< or =15%)
      of the reported end point VTEs were appropriate ICD therapies (low ICD group), or
      (2) many of the patients had implanted ICDs and the majority of the reported end
      point VTEs were appropriate ICD therapies (high ICD group). RESULTS: In the low
      ICD group comprising 3,682 patients, the hazard ratio associated with a
      nonnegative versus negative MTWA test was 13.6 (95% confidence interval [CI] 8.5
      to 30.4) and the annual event rate among the MTWA-negative patients was 0.3% (95%
      CI: 0.1% to 0.5%). In contrast, in the high ICD group comprising 2,234 patients,
      the hazard ratio was only 1.6 (95% CI: 1.2 to 2.1) and the annual event rate
      among the MTWA-negative patients was elevated to 5.4% (95% CI: 4.1% to 6.7%). In
      support of these findings, we analyzed published data from the Multicenter
      Automatic Defibrillator Trial II (MADIT II) and Sudden Cardiac Death in Heart
      Failure Trial (SCD-HeFT) trials and determined that in those trials only 32% of
      patients who received appropriate ICD therapy averted an SCD. CONCLUSION: This
      study found that MTWA testing using the spectral analytic method provides an
      accurate means of predicting VTEs in primary prevention patients without
      implanted ICDs; in particular, the event rate is very low among such patients
      with a negative MTWA test. In prospective trials of ICD therapy, the number of
      patients receiving appropriate ICD therapy greatly exceeds the number of patients
      who avert SCD as a result of ICD therapy. In trials involving patients with
      implanted ICDs, these excess appropriate ICD therapies seem to distribute
      randomly between MTWA-negative and MTWA-nonnegative patients, obscuring the
      predictive accuracy of MTWA for SCD. Appropriate ICD therapy is an unreliable
      surrogate end point for SCD.

PMID- 19168397
TI  - T-wave alternans in risk stratification of patients with nonischemic dilated
      cardiomyopathy: can it help to better select candidates for ICD implantation?
AB  - BACKGROUND: Prophylactic implantable cardioverter-defibrillator (ICD) therapy
      reduces mortality in patients with heart failure (HF) and reduced left
      ventricular ejection fraction (LVEF), but the absolute risk reduction is
      relatively small. Thus, there is a strong need to identify reliable risk
      stratifiers, particularly among patients with nonischemic cardiomyopathy (NIDCM),
      in whom the search for risk predictors has been particularly frustrating.
      OBJECTIVE: This study sought to review data regarding T-wave alternans (TWA) in
      patients with NIDCM and to discuss its potential role. METHODS: We included in a
      meta-analysis clinical trials that enrolled > or =50 NICDM patients, had a follow
      up of > or =1 year, and provided detailed data on NIDCM patients, in case of
      mixed population. Relative risks were derived from absolute numbers of events in
      abnormal (positive + indeterminate test whenever possible) TWA versus normal
      (negative) TWA group. RESULTS: Eight studies with 1,456 patients (mean age 56
      years, LVEF 30%, follow-up 25 months) were included. A negative TWA test occurred
      in 33%, and was indeterminate in 21% of the patients. The primary end point
      (VT+VF+sudden or all-cause death) occurred in 14.7% abnormal versus 3.8% normal
      TWA patients. The relative risk for the cumulative data was found to be 2.99 (95%
      confidence interval: 1.88 to 4.75). The negative predictive value was 96.2%.
      CONCLUSION: A normal TWA test identifies one-third of NIDCM patients who have a
      very good prognosis and are unlikely to significantly benefit from ICD therapy. A
      randomized clinical trial evaluating the utility of TWA in guiding therapy seems
      warranted, possibly a noninferiority trial of medical therapy only versus ICD in
      TWA-negative patients.

PMID- 19168398
TI  - Weak gender effects on transient pupillary light reflex.
AB  - We investigated the gender effects on transient pupillary light reflex (PLR) in
      healthy young adults between 18 and 22 years old. Both dark-adapted and light
      adapted PLRs were measured using green and red stimuli of different intensities.
      The results indicate that females had significantly larger relative constriction
      amplitudes than males in a dark-adapted condition. This gender effect depends on
      the stimulus intensities. The relative constriction amplitude in female subjects
      increased faster than it did in the males with the stimulus intensity. We did not
      observe any significant gender differences in the other PLR parameters, including
      latency, constriction speed, and recovery speed.

PMID- 19168399
TI  - Detection of DNA by using bio-conducting polymer-Nile blue composite electrode;
      Nile blue as an indicator.
AB  - The amplified electrochemical sensing of DNA was accomplished by electrodeposited
      PEDOT on the electrode surface and incorporation of Nile blue (NB) as redox
      active intercalator into DNA. Herein, above modified electrode called as
      PEDOT/DNA/NB composite electrode. PEDOT/DNA/NB composite electrode exhibited well
      defined redox peak at -0.35 V (Ag/AgCl) corresponding to NB. The composite
      electrode surface coverage (Gamma) and DeltaEp were compared with PEDOT/NB and
      DNA/NB modified electrode. Atomic Force microscopy (AFM), and cyclic voltammetry
      (CV) were used to characterize the PEDOT/DNA/NB composite electrode. The
      composite electrode was exhibited as surface confined redox process in neutral
      pH. The composite electrode was found to be pH dependent. The composite electrode
      exhibited catalytic property towards reduction of hydrogen peroxide (H(2)O(2)).
      The composite electrode was utilized to amperometric study and its response
      towards H(2)O(2) detection was less than 6 s and the detection limit was 0.1
      microM. Moreover, we tested PEDOT/DNA/NB composite electrode to electrocatalytic
      reduction of cytochrome c (Cyt c).

PMID- 19168400
TI  - Stimulation of direct-repeat recombination by RNA polymerase III transcription.
AB  - Eukaryotic cells have to regulate the progression and integrity of DNA
      replication forks through concomitantly transcribed genes. A transcription
      dependent increase of recombination within protein-coding and ribosomal genes of
      eukaryotic cells is well documented. Here we addressed whether tRNA transcription
      and tRNA-dependent transcription-associated replication pausing leads to genetic
      instability. Thus, we designed a plasmid based, LEU2 direct-repeat containing
      system for the analysis of factors that contribute to tRNA(SUP53)-dependent
      genetic instability. We show that tRNA(SUP53) transcription is recombinogenic and
      that recombination can be further stimulated by deletion of the 5' to 3' helicase
      Rrm3. Furthermore, tRNA(SUP53)-dependent recombination was markedly increased in
      the presence of 4-NQO in rrm3Delta cells only. The frequency of recombination
      events mediated by tRNA(SUP53) transcription does not correlate with the
      appearance and intensity of replication fork pausing sites. Our results provide
      evidence that the convergent encounter of replication and RNA polymerase III
      transcription machineries stimulates recombination, although to a lesser extent
      than RNA polymerase I or II transcription. However, there is no correlation
      between recombination and the specific replication fork pausing sites found at
      the tRNA (SUP53) gene. Our results indicate that tRNA-specific replication fork
      pausing sites are poorly recombinogenic.

PMID- 19168401
TI  - Rapid and sensitive LC-MS/MS assay for the quantitation of 20(S)-protopanaxadiol
      in human plasma.
AB  - This paper describes a rapid and sensitive method for the quantitation of 20(S)
      protopanaxadiol (PPD) in human plasma based on high-performance liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). The analyte and internal
      standard (I.S.), ginsenoside Rh(2), were extracted from plasma by liquid-liquid
      extraction and separated on a Zorbax extend C(18) analytical column using
      methanol-acetonitrile-10mM ammonium acetate (47.5:47.5:5, v/v/v) as mobile phase.
      Detection was by tandem mass spectrometry using electrospray ionization in the
      positive ion mode and multiple reaction monitoring (MRM). The assay was linear
      over the concentration range 0.1-100.0ng/ml with a limit of detection of
      0.05ng/ml. The method was successfully applied to a clinical pharmacokinetic
      study in healthy volunteers after a single oral administration of a PPD 25mg
      capsule.

PMID- 19168402
TI  - Quantification of HIV protease inhibitors and non-nucleoside reverse
      transcriptase inhibitors in peripheral blood mononuclear cell lysate using liquid
      chromatography coupled with tandem mass spectrometry.
AB  - For pharmacokinetic monitoring, measurement of antiretroviral agents in plasma is
      the gold standard. However, human immunodeficiency virus protease inhibitors
      (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) exert their
      action within the infected cell. Cell-associated concentrations may therefore
      more adequately reflect therapy outcome. Therefore, for the quantification of
      nine PIs (amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir,
      ritonavir, saquinavir and tipranavir), 1 active PI metabolite (nelfinavir M8) and
      2 NNRTIs (efavirenz and nevirapine) in lysate of peripheral blood mononuclear
      cells (PBMCs) an assay was developed and validated, using liquid chromatography
      coupled with tandem mass spectrometry. Analytes were extracted from a PBMC pellet
      by means of a one-step extraction with 50% methanol containing the internal
      standards D6-indinavir, D5-saquinavir, 13C6-efavirenz and dibenzepine.
      Chromatographic separation was performed on a reversed phase C18 column
      (150mmx2.0mm, particle size 5microm) with a quick stepwise gradient using an
      acetate buffer (pH 5) and methanol, at a flow rate of 0.25mL/min. The analytical
      run time was 10min. The triple quadrupole mass spectrometer was operated in the
      positive ion-mode and multiple reaction monitoring was used for drug
      quantification. The method was validated over a range of 1-500ng/mL in PBMC
      lysate for all analytes. The method was proven to be specific, accurate, precise
      and robust. The mean precision and accuracy was less than +/-12% at all
      concentration levels. Using the developed assay and a previously developed assay
      for these analytes in plasma, the relationship between plasma and intracellular
      pharmacokinetics and their relationship with therapy outcome can now be
      determined.

PMID- 19168403
TI  - Targeted lipidomics approach for endogenous N-acyl amino acids in rat brain
      tissue.
AB  - Great effort has been devoted to characterize signaling lipids in central nervous
      system. This has led to a search for novel strategies to characterize hitherto
      unknown lipid compositions. Here we developed two methods, one for identification
      and one for quantification, for N-acyl amino acids, a novel lipid family. The
      identification method contains a series of purification steps followed by nano
      LC/MS/MS and high-throughput screening of the datasets with a potent search
      algorithm based on fragment ion analysis. MS/MS spectra with good quality can be
      obtained with 150 fmol of targeted lipids on column with our nano-LC/MS/MS. More
      than one thousand mass spectra generated using the information dependent
      acquisition mode of Analyst QS software can be analyzed in 1 min using our home
      built software. The quantification method utilized the multiple reaction
      monitoring mode in Analyst software to measure the endogenous levels of N-acyl
      amino acids in rat brain. Using these two methods we were able to identify and
      quantify 11 previously reported N-acyl amino acids with endogenous levels ranging
      from 0.26 to 333 pmol g(-1) wet rat brain.

PMID- 19168404
TI  - De novo synthesis of trideuteromethyl esters of amino acids for use in GC-MS and
      GC-tandem MS exemplified for ADMA in human plasma and urine: standardization,
      validation, comparison and proof of evidence for their aptitude as internal
      standards.
AB  - Asymmetric dimethylarginine (ADMA, N(G),N(G)-dimethyl-L-arginine) is an
      endogenous inhibitor of nitric oxide (NO) synthesis, a potential risk factor for
      cardiovascular diseases and a powerful biochemical parameter in clinical studies.
      In our previous work we have reported on a GC-tandem MS method for the accurate
      and precise quantification of ADMA in biological fluids using de novo synthesized
      [(2)H(3)]-methyl ester ADMA (d(3)Me-ADMA) as internal standard (IS). This method
      provides basal ADMA concentrations in biological fluids that agree with those
      obtained by other groups using other validated methods for ADMA. Unanimously, de
      novo synthesized stable-isotope labeled analogues are considered not ideal IS,
      because they must be prepared in a matrix different from the biological sample.
      Recently, [2,3,3,4,4,5,5-(2)H(7)]-ADMA (d(7)-ADMA) has become commercially
      available and we took this opportunity to test the reliability of the de novo
      synthesized d(3)Me-ADMA as an IS for ADMA in GC-tandem MS. In this article, we
      report on the re-validation of the previously reported GC-tandem MS method for
      ADMA in human plasma and urine using d(7)-ADMA as IS, and on comparative
      quantitative analyses of ADMA by GC-tandem MS using d(7)-ADMA and d(3)Me-ADMA.
      After thorough standardization of d(7)-ADMA and methods validation, we obtained
      by GC-tandem MS very similar ADMA concentrations in plasma and urine using d(7)
      ADMA and d(3)Me-ADMA. The present study gives a proof of evidence for the
      aptitude of (2)H(3)-ADMA as IS in GC-tandem MS and suggests that de novo
      synthesis of stable-isotope labeled alkyl esters of amino acids and amino acid
      derivates may be a generally applicable method in mass spectrometry-based methods
      for amino acids. This approach is especially useful for amino acids for which no
      stable-isotope labeled analogues are commercially available.

PMID- 19168405
TI  - Clinical significance of serum tumour M2-PK and CA19-9 detection in the diagnosis
      of cholangiocarcinoma.
AB  - BACKGROUND/AIMS: To investigate the clinical significance of serum Tu M2-PK and
      CA19-9 detection in the diagnosis of cholangiocarcinoma. METHODS: The tumour
      markers (Tu M2-PK and CA19-9) in 115 patients with cholangiocarcinoma, 85
      patients with benign disease and 120 blood donors were detected by ELISA.
      RESULTS: The levels of serum Tu M2-PK and CA19-9 were markedly higher in the
      patients with cholangiocarcinoma than in controls (P<0.05). Tu M2-PK showed more
      sensitivity (84.2%) and specificity (90%) than CA19-9 (68.4%) and (75%).
      CONCLUSIONS: Tu M2-PK may be used as a valuable diagnosis marker in
      cholangiocarcinoma.

PMID- 19168406
TI  - Telescope sign of intussusception in Peutz-Jeghers syndrome.

PMID- 19168407
TI  - Ambulatory thyroid surgery: need for stricter patient selection criteria.
AB  - The number of outpatient surgical procedures performed in hospitals increases
      daily. In some countries, outpatient operations outnumber inpatient operations.
      The incidence of thyroid disorders and in particular, the cancer forms, has been
      increasing sharply for many years in several countries. Even if thyroid surgery
      is performed with low morbidity, no mortality, and short operation time, some
      potentially lethal complications are strong arguments against shortening of
      hospital stay. The purpose of this review is to examine the relevant updated
      published results on selection criteria measures that can be used to assess
      patients referred to short-stay surgery for thyroid disease.

PMID- 19168408
TI  - Amyloid goiter.
AB  - BACKGROUND AND AIM: Amyloidosis refers to a variety of conditions in which
      amyloid proteins are abnormally deposited in organs and/or tissues. Amyloidosis
      is a rare occurrence in thyroid gland. METHODS: A systematic review of the
      published data on amyloid goiter was carried out by searching Medline and other
      online databases (such as Scopus and Endnote) for the period from 1951 to March
      2008. A total of 127 publications (case series, single case reports and reviews)
      was found, of which 31 were case series published from February 1995 to March
      2008. Six articles have been considered for our review because they regard
      amyloid goiter as a manifestation of both primary and secondary amyloidosis (a
      total of 30 cases have been analyzed). Exclusion criterion was the presence of
      primary thyroid cancer. RESULTS: The preoperative diagnosis of amyloid goiter
      should be considered in patients with known systemic amyloidosis or with a long
      standing predisposing disease who present a rapidly growing thyroid volume in
      association with a euthyroid state. Fine-needle aspiration biopsy can be
      performed to exclude primary malignant lesions of thyroid gland and
      immunohistochemical studies can identify and characterize the amyloid deposits.
      CONCLUSION: Amyloid goiter has to be suspected in all patients with a
      progressive, rapidly growing, bilateral thyroid enlargement and a concomitant
      history of chronic inflammatory processes. Moreover, this should be suspected in
      patients who are known to have disease predisposing to amyloid deposition.

PMID- 19168409
TI  - Definitive or conservative surgery for perforated gastric ulcer?--An unresolved
      problem.
AB  - BACKGROUND: Gastric ulcer perforation has not been the focus of many studies. In
      addition there is a need to analyze the results of gastric perforation separately
      and not along with duodenal perforations, to identify the factors influencing the
      outcome and to develop strategies for its management. MATERIALS AND METHODS:
      Retrospective analysis of 54 patients presenting with gastric perforation.
      RESULTS: Mean age of the patients was 44.5 years with male preponderance.
      Morbidity following Closure of the perforation, acid reduction surgery and
      resection was not significantly different. Overall mortality was 16.6% with
      highest mortality 24.1% following simple closure. Mortality following simple
      closure and definitive surgery was not significantly different. Univariate
      analysis revealed preoperative shock, associated medical illness and surgical
      delay to be significant factors for mortality whereas on multivariate analysis,
      preoperative shock was the only independent predictor of mortality. Mortality
      increased with increasing Boey score but the association between the type of
      surgery and probability of survival was not statistically significant.
      CONCLUSION: Boey risk score is useful in predicting the outcome of surgical
      treatment for gastric perforation. Definitive surgery is not associated with
      greater morbidity or mortality compared to simple closure.

PMID- 19168410
TI  - Labial ring flap: a new flap for metaidoioplasty in female-to-male transsexuals.
AB  - OBJECTIVE: To describe the technical details of our experience in performing
      metaidoioplasty. PATIENTS AND METHODS: After the first officially approved sex
      reassignment surgery on a patient with transsexualism was performed in Japan, we
      performed metaidoioplasties on 69 female-to-male transsexuals between 1998 and
      2007. Oophorohysterectomy and metaidoioplasty were performed by a one-stage
      procedure. Hage's technique was used on the first 26 cases. The labial ring flap
      technique was performed on 43 patients (aged 18-33 years) after 2005. This new
      technique uses all the labia minora skin incorporated with the anterior vaginal
      flap for urethral lengthening. The clitoral chordee is also released by this
      procedure. RESULT: Using this method, we obtained a neo-urethra of a good
      diameter and a more male-like appearance for external genitalia along with a
      minipenis. The postoperative course was uneventful in 28 of 43 cases. Urethral
      fistula occurred in 12 cases, which was spontaneously closed in eight cases. Four
      other cases required secondary repair. Three cases with neo-urethral stenosis
      were treated by urethral dilation. Of the 43 cases, 28 can void in a standing
      position. For five patients who desired a larger phallus, various phalloplasty
      techniques were performed subsequently. CONCLUSION: Satisfactory urine stream and
      appearance were achieved. Metaidoioplasty with minimal scarring can be selected
      independently or as the first step followed by phalloplasty if the patient
      requires such an operation.

PMID- 19168411
TI  - [The Kidney Foundation: results of the last two years].

PMID- 19168412
TI  - Comparative bioequivalence and pharmacokinetics of ciprofloxacin in healthy male
      subjects.
AB  - Pharmacokinetics and bioequivalence studies of two ciprofloxacin tablet brands
      (trial batch of ciprofloxacin (Test) & Reference) were conducted in 14 healthy
      male volunteers after oral administration. Each brand (test and reference)
      consisted of 500 mg of ciprofloxacin. The drug was analyzed in plasma samples
      with a microbiological assay using Streptococcus faecalis as test organism. The
      elimination half-life of 3.00 +/- 0.21 and 3.28 +/- 0.11 h was calculated for
      both brands. The peak plasma concentrations of (3.59 +/-0.26 ug/mL) and (3.34 +/-
      1.20 ug/mL) was attained in about 1.48 +/- 0.11 hour and 1.47+/-0.05 for both
      Test and Reference ciprofloxacin respectively. The mean +/- SE values for total
      area under the curve (AUC O-alpha) were 26.15 +/- 1.35, and 24.95 +/- 0.93 hmg/1
      for both test and reference tablets respectively. The mean +/- SE values of
      clearance were 24.83+/-1.63 and 24.73+/-1.11 1/h for both formulations
      respectively. The ratio of elimination rate constant Kel [l/h] was 1.14 percent
      difference between the test and reference tablets and likewise, half-life
      (t1/2beta) expressed in hours showed the ratio of 0.91 percent. This study
      indicated that all the pharmacokinetic and bioequivalence parameters for both
      ciprofloxacin formulations are statistically non-significant, hence both
      formulations are bioequivalent.

PMID- 19168413
TI  - Simultaneous determination of the two non-steroidal anti-inflammatory drugs ;
      diflunisal and naproxen in their tablets by chemometric spectrophotometry and
      HPLC.
AB  - Chemometric spectrophotometry and HPLC were applied to the simultaneous
      determination of the two non-steroidal anti-inflammatory drugs; diflunisal (I)
      and naproxen (II). The applied chemometric techniques are multivariate methods
      including classical least squares (CLS), principal component regression (PCR) and
      partial least squares (PLS); and the second derivative of the ratio spectra
      ((2)D(r)) method. To develop the multivariate methods, the UV absorption spectra
      of the standard solutions of the training and validation sets in methanol were
      recorded in the range of 242-274 nm at 2 nm intervals. The specificity of the
      studied multivariate methods has been tested. In the (2)D(r) method, analytical
      signals at 235 and 259 nm were selected for the determination of (I) and (II),
      respectively. The HPLC method depends on reversed-phase separation using C18
      column. The mobile phase consists of a mixture of acetonitrile - acetate buffer
      (pH 4.2; 50 mM) (60:40, v/v). The UV detector was set at 255 nm. The developed
      methods were validated and successfully applied to the simultaneous determination
      of (I) and (II) in their tablets. The assay results obtained using the
      chemometric methods were statistically compared to those of the HPLC method and
      good agreement was observed.

PMID- 19168414
TI  - Determination of benzoic acid and salicylic acid in commercial benzoic and
      salicylic acids ointments by spectrophotometric method.
AB  - Commercial benzoic acid and salicylic acid ointments have been analyzed for
      benzoic acid and salicylic acid content by using a spectrophotometric method.
      Since benzoic acid and salicylic acid exhibit overlapping spectra, absorbance
      measurements are made at two wavelengths, i.e. 271 nm and 303 nm in ethanol
      (96%v/v) for simultaneous determination of the two compounds. The method is
      direct and involves only one step of absorbance measurement in the assay. The
      precision of the method, based on the analysis of synthetic mixtures of the two
      compounds, is within 2%. The recoveries of benzoic acid and salicylic acid in the
      ointments range from 99.9 to 100.6% and 99.5 to 101.3%, respectively and are
      comparable with those of the USP method (99.8 to 100.5% and 100.2 to 101.7%,
      respectively). The proposed method is simple, rapid, precise and convenient for
      the assay of benzoic acid and salicylic acid in commercial preparations.

PMID- 19168415
TI  - The effects of all-trans retinoic acid on blood cells in rat's embryo.
AB  - All-trans retinoic acid (ATRA) has beneficial and teratogenicity effects when
      used in a variety conditions. The objectives of this study were to determine the
      effects of ATRA on the Progenitors of red blood cell and platelets in rat's
      embryo. Single oral dose (100 mg/kg) of ATRA was administered to rat on gestation
      day (GD) 10 and fetuses were observed on GD 18 and compared with untreated group.
      In the experimental embryos of GD 18, the mean number of red blood cells (RBC,
      10.5%) and platelets number (15%) were decreased. There was a significant
      relationship in RBC and platelets count. The mean diameter of RBC and nucleated
      red blood (NRBC) were compared in two groups. There was no significant
      relationship between experimental and control groups, except in NRBC diameter.
      Thus, the present data shows that ATRA may have negative effects on
      proliferation, differentiation and maturation of erythroid cells and platelets,
      without having any deleterious effects on the dimenation of RBC.

PMID- 19168416
TI  - Application of UV-spectrophotometric methods for estimation of tenofovir
      disoproxil fumarate in tablets.
AB  - Two new, simple and cost effective UV-spectrophotometric and first order
      derivative methods were developed for estimation of tenofovir disoproxil fumarate
      in bulk and tablets. Tenofovir disoproxil fumarate was estimated at 260 nm in
      0.1N HCl. In first order derivative, it showed amplitude at 273 nm. In both the
      methods linearity was found to be in the range of 5-40 micro/ ml; for UV
      spectrophotometric method (Y=0.02586 x +0.0083; r(2)=0.9999) and for first order
      derivative spectrophotometric method (Y=0.00132 x +0.00035; r(2)=0.9995),
      respectively. These methods were tested and validated for various parameters
      according to USP guidelines. The quantitation limits were found to be 1.546 and
      1.986 micro/ ml, for both the methods. The proposed methods were successfully
      applied for the determination of tenofovir disoproxil fumarate in pharmaceutical
      formulations. The results demonstrated that the procedure is accurate, precise
      and reproducible (relative standard deviation <2%), while being simple, cheap and
      less time consuming and can be suitably applied for the estimation of tenofovir
      disoproxil fumarate in different dosage forms.

PMID- 19168417
TI  - Screening of antioxidant properties of seven Umbelliferae fruits from Iran.
AB  - Antioxidative activities (IC(50)) of ethanol extracts from seven Umbelliferae
      fruits (Bunium persicum, Coriandrum sativum, Cuminum cyminum, Foeniculum vulgare,
      Heracleum persicum, Pimpinella anisum and Trachyspermum copticum) have been
      studied by the DPPH (2,2'-diphenyl-1-picrylhydrazyl) radical scavenging test. All
      the studied extracts showed antioxidant capability and P. anisum extract
      exhibited the strongest activity. The scavenging activity of the extracts in
      decreasing order was: P. anisum> T. copticum> C. cyminum> F. vulgare > or = B.
      persicum > or = C. sativum> H. persicum. The extracts were also investigated
      regarding their total flavonoid contents by the AlCl3 technique. The decreasing
      order of the flavonoid content of the extracts was: C. cyminum > T. copticum> P.
      anisum > or = H. persicum > or = B. persicum > or = F. vulgare > or = C. sativum.
      However, a favorable correlation was not found between the antioxidant activity
      and the total flavonoid content of the extracts. As well, the most active extract
      (i.e. P. anisum) was partitioned with n-hexane, chloroform and ethyl acetate to
      yield three organic fractions together with the remaining aqueous fraction. The
      antioxidative activities (IP%) and flavonoid contents of the fractions were also
      determined. The ethyl acetate fraction exhibited the highest activity and
      content. A positive correlation was found between the antioxidant potency and
      flavonoid content of the fractions.

PMID- 19168418
TI  - Stability study of ambroxol hydrochloride sustained release pellets coated with
      acrylic polymer.
AB  - The aim of the present study is to perform stability study of ambroxol
      hydrochloride sustained release pellets stored in different storage conditions.
      The drug loaded beads were prepared by extrusion-spheronization technology then
      coated with ammonio methacrylate copolymer type A (Eudragit RL 30 D) and ammonio
      methacrylate copolymer type B (Eudragit RS 30 D) at a ratio of 2:3 (8% polymer by
      weight on dry basis) in fluid bed coater (Wurster column). Stability study of
      pellets was performed as capsule dosage form in aluminium-PVDC packaging mode at
      room temperature, 40 degrees C, 40 degrees C/75%RH & 30 degrees C/70%RH for three
      months. After one month the shape & size of the pellets was changed in all
      conditions. The color of the pellets remains unchanged up to the 2nd month in all
      conditions except at 40 degrees C/75%RH and in this case some pellets become
      brown. But after 3rd month, pellets become brownish in all conditions except at
      room temperature. At RT the color of pellets remains unchanged during the
      stability study. The mean drug content decreased gradually in all conditions. In
      acid media the initial drug release was 23% but after 1st month it was decreased
      to 13-15% in all conditions. In the buffer media (pH 6.8) the drug release was
      increased a little bit in all conditions except at 30 degrees C/70%RH with the
      passes of storage time. Stability studies at 30 degrees C/70%RH revealed
      consistent drug release (f(2)>50) throughout the stability period. The physical
      properties of pellets as well as the in vitro release profile of the drug was
      found to be a function of the different storage conditions as well as the physico
      chemical nature of the polymers.

PMID- 19168419
TI  - Multidrug resistant gram-negative bacteria in clinical isolates from Karachi.
AB  - A total of 54 gram-negative bacteria obtained from various pathological labs and
      hospitals of Karachi were screened for their resistance to ampicillin,
      chloramphenicol, gentamycin, kanamycin, neomycin, streptomycin and tetracycline
      antibiotics. Of the 54 bacteria, 50 were resistant to one or more antibiotics.
      Among the resistant bacteria, 13 out of 28 were found to transfer their
      resistances by conjugation. This indicates that at least 46% of clinical gram
      negative bacteria in Karachi possess various types of transferable R plasmids,
      such as pAK5, pAK9, pAK10, pAK11, pAK12, pAK13, pAK14, pAK15, pAK16, pAK17,
      pAK18, pAK19, pAK20 and pAK21. The non-conjugative R plasmids included pMT14 and
      pZ26. Only pAK15 showed 26% segregation even after 20 consecutive transfers in
      plain broth (spontaneous segregation) whereas only pAK15 and pAK16 showed any
      significant loss of their markers in curing by acridine orange. The stability of
      R plasmids is more dangerous from clinical point of view.

PMID- 19168420
TI  - Evaluation of beneficial effects of antioxidant properties of aqueous leaf
      extract of Andrographis paniculata in STZ-induced diabetes.
AB  - The beneficial effects of antioxidant properties Andrographis paniculata
      (Andrographis) were studied in the diabetic animals. Hyperglycemia,
      characteristic feature of diabetes mellitus leads to decreased antioxidant
      defense and hence development of oxidative stress, which in involved in the
      etiology of development of diabetic complications. The evidences suggest that
      good glycemic control and/or use of antioxidants may play an important role in
      the prevention of complications associated with diabetes. Diabetes was induced
      with single intraperitoneal injection of streptozotocin (45 mg/kg, i.p) dissolved
      in freshly prepared citrate buffer (pH 4.5), resulted in elevation of blood
      glucose levels, decrease in the superoxide dismutase and catalase activity. Oral
      administration of Andrographis (400 mg/kg, p.o) resulted in significant decrease
      in the blood glucose levels and increase in the activity of SOD and catalase. In
      conclusion Andrographis decreased the blood glucose levels in diabetic animals
      may be due to its antioxidant properties.

PMID- 19168421
TI  - New synthesis of aminorhodanin and condensed derivatives.
AB  - Aminorhodanins are heterocyclic compounds of dithiocarbazoyl which include
      sulphur and nitrogen in their structures. Different research studies have been
      performed on rhodanin and it's condensed derivatives and several reports have
      been issued indicating their antimicrobial properties. In the present work, first
      a new method has been developed for production of aminorhodanin, which include
      one more nitrogen atom in third position compare to rhodanins molecule, then
      condensed reactions with aldehydes have been investigated. The probable
      biological properties of produced compounds will be investigated in another
      research study.

PMID- 19168422
TI  - Potential of carnuba wax in ameliorating brittle fracture during tableting.
AB  - Carnuba wax (as binder) forms hard tablets even at low compression load
      attributable to its high plasticity. The aim of the present study is to
      investigate its potential in ameliorating brittle fracture (i.e., lamination and
      capping) a problem often encountered during tableting. Granules of paracetamol
      (test drug) were made by triturating the drug powder with the melted wax or
      starch mucilage (20%w/v). Resulting granules were separated into different size
      fractions which were separately compressed into tablets with and without a centre
      hole (as in- built defect) using different compression loads. The tablets were
      evaluated for tensile strength and the data used to calculate the brittle
      fracture index (BFI), using the expression: BFI = 0.5(T/T(0)-1) where T0 and T
      are the tensile strength of tablets with and without a centre hole respectively.
      The BFI values were significantly lower (p<0.05) in tablets made with carnuba wax
      compared with tablets made with maize starch as binders. Increase in particle
      size of the granules or lowering of the compression load further ameliorated the
      brittle fracture tendency of the tablets. Using granules with the larger particle
      size (850microm) and applying the lowest unit of load (6 arbitrary unit on the
      load scale of the tableting machine) the BFI values were 0.03 (carnuba wax
      tablets) and 0.11 (maize starch tablets). When the conditions were reversed
      (i.e., a highest load, 8 units and the smallest particle size, 212microm) the BFI
      values now became 0.17 (carnuba wax tablets) and 0.26 (maize starch tablets). The
      indication is that the use of large granules and low compression loads to form
      tablets can further enhance the potential of carnuba wax in ameliorating brittle
      fracture tendency of tablets during their manufacture.

PMID- 19168423
TI  - Ischemic stroke: prevalence of modifiable risk factors in male and female
      patients in Pakistan.
AB  - Stroke is the commonest neurological cause of morbidity and mortality all over
      the world being the third leading cause of death. Estimation of stroke risks in
      population is not only helpful for healthcare providers but also important to
      identify persons at elevated risk and to select proper treatments in clinical
      trials. The aim of the present study was to identify the prevalence of common
      modifiable risk factors for ischemic stroke in Pakistan. Patients of either sex
      above the age of 25 yrs who were admitted to Neurology Ward or came to OPD in
      Jinnah Post Graduate Medical Centre were included in the study. Type of stroke
      was identified by brain CT scans or MRI and risk factors for stroke and other
      details were noted on a proforma. Out of 55 patients studied for present study,
      78% were males and 22% were females. Most of them belonged to low socioeconomic
      status and almost 50% were having family history of stroke. Most of the patients
      had multiple risk factors which included: hypertension (65%), smoking (32%),
      diabetes mellitus (36.3%), dyslipidemia (32.7%), coronary artery disease (9%),
      obesity (18%), epilepsy (16.3%) and left ventricular hypertrophy (3.6%). On the
      basis of these findings, it can be concluded that hypertension, smoking,
      dyslipidemia and diabetes mellitus are major risk factors for stroke and might be
      considered as main targets for primary and secondary prevention of stroke.

PMID- 19168424
TI  - A novel RP-HPLC method for the determination of bharangin in Ghantu bharangi
      crude extracts.
AB  - An accurate, simple, reproducible and sensitive RP-HPLC method for the
      determination of bharangin has been developed and validated. The separation of
      bharangin and 2-nitroaniline (internal standard) was achieved on Supelcosil LC-18
      (3micro, 150 x 4.6 mm i.d.) column using UV detection at 388 nm. The mobile phase
      was consisting of methanol and 0.01 M KH(2)PO(4) buffer (pH 3.0, adjusted with
      ortho-phosphoric acid) (75:25, % v/v). The linear range of detection for
      bharangin was found to be 10-50 ng/ml. Intra-and inter-days assay relative
      standard deviations were less than 3.21. The method has been successfully applied
      to the determination of bharangin in various crude extracts. The method has been
      shown to be linear, reproducible, specific, and rugged.

PMID- 19168425
TI  - The analgesic and anti-inflammatory activities of the extract of Albizia lebbeck
      in animal model.
AB  - The extract of the bark of Albizia lebbeck Benth. obtained by cold extraction of
      mixture of equal proportions of petroleum ether, ethyl acetate and methanol was
      chosen for pharmacological screening. In rat paw edema model induced by
      carrageenan, the extract at the 400 mg/kg dose level showed 36.68% (p<0.001)
      inhibition of edema volume at the end of 4h. In the acetic acid-induced writhing
      test, the extract at the 200 and 400 mg/kg dose level showed 39.9% and 52.4 %
      inhibition of writhing, respectively. In radiant heat tail-flick method the crude
      extract produced 40.74% (p<0.001) and 61.48% (p<0.001) elongation of tail
      flicking time 30 minutes after oral administration at the 200 and 400 mg/kg dose
      level, respectively.

PMID- 19168426
TI  - Conformational analysis (geometry optimization) of nucleosidic antitumor
      antibiotic showdomycin by Arguslab 4 software.
AB  - Showdomycin is a naturally maleimide antitumor antibiotic of the C-nucleoside, it
      inhibits the nucleic acid synthesis in bacteria. Conformational analysis and
      geometry optimization of showdomycin was performed according to the Hartree-Fock
      (HF) calculation method by ArgusLab 4.0.1 software. The minimum potential energy
      is calculated by geometry convergence function by ArgusLab software. The most
      feasible position for the drug to interact with the receptor was found to be
      0.269696 K.cal/mole.

PMID- 19168427
TI  - Antinociceptive effects of hydroalcoholic extract of Thymus vulgaris.
AB  - Previous investigation has shown that Thymus Vulgaris (TV) modulates pain. The
      aim of this work was to examine the role of TV on acute and chronic pain and
      compares its effect with dexamethasone (DEX) and stress (ST) by using hot plate,
      tail flick and formalin tests in mice. In this study male albino mice (25-30 g.)
      in 21 groups (n=147) were used. TV (100, 500 and 1000 mg/kg), DEX (0.5, 1 and 2
      mg/kg) and vehicle (VEH) were injected 30 minutes before pain assessment tests.
      Stress was applied by 1 min swimming in cold water (18-22 degrees ). Acute and
      chronic pain was assessed by hot plate, tail flick and formalin tests. For
      assessment of the role of opioid receptors in antinoceception of TV extract,
      Naloxon (NAL, 2mg/kg, ip) as opioid receptor antagonist was injected before the
      injection of the more effective dose (500 mg/kg) of TV extract. Results indicated
      that TV, DEX and ST have analgesic effects in all tests (P<0.01 in comparison
      with control group). Above findings showed that TV extract, DEX and ST have
      modulatory effects on acute and chronic pain. Further research is required to
      determine the mechanisms by which TV extract has an inhibitory effect on pain
      sensation.

PMID- 19168428
TI  - Effect of Clausena dentata (Willd.) M. Roem. against paracetamol induced
      hepatotoxicity in rats.
AB  - Ethanol extract of Clausena dentata (Willd.) M. Roem (Rutaceae) was evaluated for
      hepatoprotective activity in rats. The plant extract (250 mg/kg, p.o.) showed a
      remarkable hepatoprotective activity against acetaminophen-induced hepatotoxicity
      as judged from the serum markers for liver damage. Acetaminophen induced a
      significant rise in aspartate amino transferase (AST), alanine amino transferase
      (ALT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate
      transpeptidase (GGTP) and decrease in total protein. Treatment of rats with
      ethanol extract (250 mg/kg) significantly (P<0.001) altered serum marker enzymes
      levels to near normal against acetaminophen treated rats. The activity of the
      extract was comparable to the standard drug, silymarin (50 mg/kg, p.o.).
      Histopathological changes of liver sample were compared with respective control.
      Results indicate that Clausena dentata possesses hepatoprotective effect on
      acetaminophen-induced hepatotoxicity in rats.

PMID- 19168429
TI  - St. John's Wort modulates brain regional serotonin metabolism in swim stressed
      rats.
AB  - Present study has investigated acute effects of Saint Johns Wort (SJW, 500mg/kg)
      administration on behavioral, neuroendocrine responses and serotonergic activity
      following forced swim test (FST) exposure in rats. The results show that SJW
      increased swimming and climbing behaviour of rats during FST exposure. Swim
      stress produced significant reduction in serum total tryptophan (P<0.01),
      increase in corticosterone (P<0.01) and 5-hydroxytryptamine (serotonin, 5-HT)
      turnover in hypothalamus by 100% (P<0.01), amygdala by 148 % (P<0.01), and
      hippocampus by 41% (P<0.05) when compared with unstressed saline injected group.
      SJW in swim stressed rats when compared with saline injected stressed rats
      altered neither lowered serum tryptophan nor enhanced HPA axis response, however
      5HT was found to be increased by 110% (P<0.01), 163% (P<0.01) and 172% (P<0.01),
      in hypothalamus, amygdala and hippocampus respectively. 5-hydroxyindoleacetic
      acid (5HIAA) was also found to be increased in hypothalamus by 74% (P<0.01),
      amygdala by 45% (P<0.01) and hippocampus by 143.5% (P<0.01). Further SJW
      administration in unstressed rats showed decrease in tryptophan (P<0.01),
      increase in corticosterone (P<0.01), 5HT was found to be decreased in
      hypothalamus (47%, P<0.01) and in amygdala (13 %, P<0.05) with no change in
      hippocampus, while 5HIAA was found increased in hypothalamus by 58 %(P<0.01),
      amygdale by 203 % (P<0.01) and hippocampus by 171% (P<0.01). The data shows that
      SJW affects circulating tryptophan and corticosterone in absence of conditioned
      stress but not in its presence. In conclusion, SJW increases intraneuronal 5HT
      metabolism but inhibits its release under adverse conditions proving its
      anxiolytic property. Thus, these effects produced by the SJW add to our
      understanding of the interactions between SJW and stress induced behavioral,
      neuroendocrine and serotonergic alterations.

PMID- 19168430
TI  - Total phenolic content, antioxidant and antimicrobial activities of some
      medicinal plants.
AB  - Crude extracts from Inula aucherana, Fumaria officinalis, Crocus sativus, Vicum
      album, Tribulus terestris, Polygonatum multiflorum, Alkanna tinctoria and
      Taraxacum officinale were screened for their in vitro antioxidant and
      antimicrobial properties. Total phenolic content of extracts from these plants
      were also determined. beta-carotene bleaching assay and Folin-Ciocalteu reagent
      were used to determine total antioxidant activity and total phenols of plant
      extracts. Antimicrobial activity was determined by using disk diffusion assay.
      Antioxidant activity and total phenolic content varied among plants used and
      Viscum album and Crocus sativus had the highest antioxidant (82.23%) and total
      phenolic content (42.29 mgGAE/g DW), respectively. The methanol extracts from
      Vicum album and Alkanna tinctoria showed antimicrobial activity against 9 out of
      32 microorganisms, however extract from Inula aucherana showed antimicrobial
      activity against 15 out of 32 microorganisms. The results provided evidence that
      the studied plant might indeed be potential sources of natural antioxidant and
      antimicrobial agents.

PMID- 19168431
TI  - Kohl (surma): retrospect and prospect.
AB  - Kohl, since antiquity has always been given a prime importance in ophthalmology
      for the protection and treatment of various eye ailments. However, for decades
      various conflicting reports in the literature have been published relating to
      Kohl application to eyes being responsible for causing higher blood lead
      concentration, which may cause lead poisoning. While at the same time, a number
      of research studies and reports have also been published negating any such links
      with increased blood lead level upon Kohl (surma) application. In view of the
      above mentioned facts, this review article is written with the objective to
      highlight various data from past and present research studies and reports about
      Kohl, so as to provide valuable information to both the users and the research
      workers about it's scientific background and effects when applied into eyes. A
      large number of items and topics (such as Kohl, surma, eye cosmetic, traditional
      eye preparations, environmental lead pollution, galena, lead sulphide etc.) have
      been taken into consideration while compiling this review article. In conclusion,
      the authors of this review article feel that the relation between Kohl and
      toxicity or increased blood lead concentration upon it's application to eyes as
      reported elsewhere is likely to be more of theoretical nature rather than a
      practical health hazard.

PMID- 19168432
TI  - Macrophage depletion in hypertensive rats accelerates development of
      cardiomyopathy.
AB  - Inflammation contributes to the process of ventricular remodeling after acute
      myocardial injury. To investigate the role of macrophages in the chronic process
      of cardiac remodeling, they were selectively depleted by intravenous
      administration of liposomal clodronate in heart failure-prone hypertensive Ren-2
      rats from the age of 7 until 13 weeks. Plain liposomes were used for comparison.
      Liposomal clodronate treatment reduced the number of blood monocytes and
      decreased the number of macrophages in the myocardium. Compared to plain
      liposomes, liposomal clodronate treatment rapidly worsened left ventricular
      ejection function in hypertensive rats. Liposomal clodronate- treated Ren-2 rat
      hearts showed areas of myocyte loss with abundant inflammatory cell infiltration,
      predominantly comprising CD4 positive T lymphocytes. The current study showed
      that lack of macrophages was associated with earlier development of myocardial
      dysfunction in hypertensive rats. Modulation of macrophage function may be of
      value in the evolution of cardiomyopathy.

PMID- 19168433
TI  - Challenges in the clinical development requirements for the marketing
      authorization of new medicines in southeast Asia.
AB  - A rapid growth of investment into clinical research and new drug development has
      manifested itself by an exponential increase of new products coming onto the
      worldwide market. The emerging pharmaceutical and biotech markets in Southeast
      Asia are believed to be extremely promising from a commercial point of view in
      the next decade. The unique position of the Asian market and the diversity in
      clinical research initiatives are linked with diverse regulatory requirements for
      clinical development and registration of new medicines. Some of these differences
      have an impact on timelines for marketing authorizations in South Korea, China,
      Thailand, Japan, Singapore, and other countries. One of the approaches to
      streamlining regulatory strategy in different countries is the initiation of
      multicountry international clinical trials trying to address requirements and
      allowing registration in several regional countries simultaneously. Increasing
      cooperation between South Asian countries in relation to regulatory requirements
      and clinical development will facilitate the registration of innovative medicines
      in this rapidly developing region of the world and enable improved cohesiveness
      between countries in a drug safety framework.

PMID- 19168434
TI  - Behavioral status of children with cryptogenic localization-related epilepsy.
AB  - Using the Child Behavior Checklist, behavior of 51 children with cryptogenic
      localization-related epilepsy was studied. According to parent report, children
      with cryptogenic localization-related epilepsy scored in the clinical range on
      the subscales "internalizing behavior," ''total behavior,'' and "attentional
      problems.'' No relation between the epilepsy factors seizure frequency, age at
      onset, duration of epilepsy or the number of antiepileptic drugs, and the
      subscales of the Child Behavior Checklist was found. Only for seizure type a
      relationship was found. Although in the normal range, the more severe the seizure
      type, the more delinquent, aggressive, and externalizing behavioral problems.
      Other studies have demonstrated that in children with epilepsy, internalizing
      problems are more common than externalizing problems, and that attentional,
      social, and thought problems are relatively specific. Therefore, we can conclude
      that the behavioral problems we found in our cohort are not very different from
      behavioral problems described in other epilepsy types.

PMID- 19168435
TI  - CXCL10 inhibits viral replication through recruitment of natural killer cells in
      coxsackievirus B3-induced myocarditis.
AB  - Coxsackievirus (CV)B3 is the primary cause of viral myocarditis. We previously
      observed CXC chemokine ligand 10 (CXCL10) upregulation in the myocardium early in
      infection. However, the impact of CXCL10 in CVB3-induced myocarditis is unknown.
      Using isolated primary mouse cardiomyocytes we demonstrated for the first time
      that cardiomyocytes can express CXCL10 on interferon-gamma stimulation. To
      explore the role of CXCL10 in CVB3-induced myocarditis, both CXCL10 transgenic
      and knockout mice were used. Following CVB3 challenges, the viral titer in the
      hearts inversely correlated with the levels of CXCL10 at early phase of infection
      before visible immune infiltration. Furthermore, as compared with the control
      mice, the decreased virus titers in the CXCL10 transgenic mouse hearts led to
      less cardiac damage and better cardiac function and vice verse in the knockout
      mice. This antiviral ability of CXCL10 might be through recruitment of natural
      killer (NK) cells to the heart and increased interferon-gamma expression early in
      infection. At day 7 postinfection, with massive influx of mononuclear cells the
      expression of CXCL10 enhanced the infiltration of CXCR3(+) cells, CD4(+), and
      CD8(+) T cells, as well as the expression of associated inflammatory cytokines.
      However, the augmented accumulation of these immune cells and associated
      cytokines failed to alter the viral clearance and mice survival. These results
      suggest the protective role of CXCL10 during the early course of CVB3 infection,
      which is attributed to the recruitment of NK cells. Nonetheless, CXCL10-directed
      chemoattractant effect is not sufficient for host to clear the virus in the
      heart.

PMID- 19168436
TI  - TRPC1 associates with BK(Ca) channel to form a signal complex in vascular smooth
      muscle cells.
AB  - TRPC1 (transient receptor potential canonical 1) is a Ca(2+)-permeable cation
      channel involved in diverse physiological function. TRPC1 may associate with
      other proteins to form a signaling complex, which is crucial for channel
      function. In the present study, we investigated the interaction between TRPC1 and
      large conductance Ca(2+)-sensitive K(+) channel (BK(Ca)). With the use of
      potentiometric fluorescence dye DiBAC(4)(3), we found that store-operated Ca(2+)
      influx resulted in membrane hyperpolarization of vascular smooth muscle cells
      (VSMCs). The hyperpolarization was inhibited by an anti-TRPC1 blocking antibody
      T1E3 and 2 BK(Ca) channel blockers, charybdotoxin and iberiotoxin. These data
      were confirmed by sharp microelectrode measurement of membrane potential in VSMCs
      of intact arteries. Furthermore, T1E3 treatment markedly enhanced the membrane
      depolarization and contraction of VSMCs in response to several contractile
      agonists including phenylephrine, endothelin-1, and U-46619. In
      coimmunoprecipitation experiments, an antibody against BK(Ca) alpha-subunit
      [BK(Ca)(alpha)] could pull down TRPC1, and moreover an anti-TRPC1 antibody could
      reciprocally pull down BK(Ca)(alpha). Double-labeling immunocytochemistry showed
      that TRPC1 and BK(Ca) were colocalized in the same subcellular regions, mainly on
      the plasma membrane, in VSMCs. These data suggest that, TRPC1 physically
      associates with BK(Ca) in VSMCs and that Ca(2+) influx through TRPC1 activates
      BK(Ca) to induce membrane hyperpolarization. The hyperpolarizing effect of TRPC1
      BK(Ca) coupling could serve to reduce agonist-induced membrane depolarization,
      thereby preventing excessive contraction of VSMCs to contractile agonists.

PMID- 19168437
TI  - ADAMTS-7 mediates vascular smooth muscle cell migration and neointima formation
      in balloon-injured rat arteries.
AB  - The migration of vascular smooth muscle cells (VSMCs) plays an essential role
      during the development of atherosclerosis and restenosis. Extensive studies have
      implicated the importance of extracellular matrix (ECM)-degrading proteinases in
      VSMC migration. A recently described family of proteinases, a disintegrin and
      metalloproteinase with thrombospondin motifs (ADAMTs), is capable of degrading
      vascular ECM proteins. Here, we sought to determine whether ADAMTS-7 is involved
      in VSMC migration and neointima formation in response to vascular injury. ADAMTS
      7 protein accumulated preferentially in neointima of the carotid artery wall
      after balloon injury. In primary VSMCs, ADAMTS-7 level was enhanced by the
      proinflammatory cytokine tumor necrosis factor alpha and growth factor platelet
      derived growth factor-BB. ADAMTS-7 overexpression greatly accelerated and small
      interfering RNA knockdown markedly retarded VSMC migration/invasion in vitro. In
      addition, luminal delivery of ADAMTS-7 adenovirus to carotid arteries exacerbated
      intimal thickening nearly sixfold 7 days after injury. Conversely, perivascular
      administration of ADAMTS-7 small interfering RNA but not scramble small
      interfering RNA to injured arteries attenuated intimal thickening by 50% at 14
      days after injury. Furthermore, ADAMTS-7 mediated degradation of the vascular ECM
      cartilage oligomeric matrix protein (COMP) in injured vessels. Replenishing COMP
      circumvented the promigratory effect of ADAMTS-7 on VSMCs. Enforced expression of
      COMP significantly suppressed VSMC migration and neointima formation postinjury,
      which indicates that ADAMTS-7 facilitated intimal hyperplasia through degradation
      of inhibitory matrix protein COMP. ADAMTS-7 may therefore serve as a novel
      therapeutic target for atherosclerosis and postangioplasty restenosis.

PMID- 19168438
TI  - A single serine in the carboxyl terminus of cardiac essential myosin light chain
      1 controls cardiomyocyte contractility in vivo.
AB  - Although it is well known that mutations in the cardiac essential myosin light
      chain-1 (cmlc-1) gene can cause hypertrophic cardiomyopathy, the precise in vivo
      structural and functional roles of cMLC-1 in the heart are only poorly
      understood. We have isolated the zebrafish mutant lazy susan (laz), which
      displays severely reduced contractility of both heart chambers. By positional
      cloning, we identified a nonsense mutation within the zebrafish cmlc-1 gene to be
      responsible for the laz phenotype, leading to expression of a carboxyl-terminally
      truncated cMLC-1. Whereas complete loss of cMLC-1 leads to cardiac acontractility
      attributable to impaired cardiac sarcomerogenesis, expression of a carboxyl
      terminally truncated cMLC-1 in laz mutant hearts is sufficient for normal cardiac
      sarcomerogenesis but severely impairs cardiac contractility in a cell-autonomous
      fashion. Whereas overexpression of wild-type cMLC-1 restores contractility of laz
      mutant cardiomyocytes, overexpression of phosphorylation site serine 195
      deficient cMLC-1 (cMLC-1(S195A)) does not reconstitute cardiac contractility in
      laz mutant cardiomyocytes. By contrast, introduction of a phosphomimetic amino
      acid on position 195 (cMLC-1(S195D)) rescues cardiomyocyte contractility,
      demonstrating for the first time an essential role of the carboxyl terminus and
      especially of serine 195 of cMLC-1 in the regulation of cardiac contractility.

PMID- 19168439
TI  - p66Shc links alpha1-adrenergic receptors to a reactive oxygen species-dependent
      AKT-FOXO3A phosphorylation pathway in cardiomyocytes.
AB  - p66Shc is an adapter protein that is induced by hypertrophic stimuli and has been
      implicated as a major regulator of reactive oxygen species (ROS) production and
      cardiovascular oxidative stress responses. This study implicates p66Shc in an
      alpha(1)-adrenergtic receptor (alpha(1)-AR) pathway that requires the cooperative
      effects of protein kinase (PK)Cepsilon and PKCdelta and leads to AKT-FOXO3a
      phosphorylation in cardiomyocytes. alpha(1)-ARs promote p66Shc-YY(239/240)
      phosphorylation via a ROS-dependent mechanism that is localized to caveolae and
      requires epidermal growth factor receptor (EGFR) and PKCepsilon activity.
      alpha(1)-ARs also increase p66Shc-S(36) phosphorylation via an EGFR
      transactivation pathway involving PKCdelta. p66Shc links alpha(1)-ARs to an AKT
      signaling pathway that selectively phosphorylates/inactivates FOXO transcription
      factors and downregulates the ROS-scavenging protein manganese superoxide
      dismutase (MnSOD); the alpha(1)-AR-p66Shc-dependent pathway involving AKT does
      not regulate GSK3. Additional studies show that RNA interference-mediated
      downregulation of endogenous p66Shc leads to the derepression of FOXO3a-regulated
      genes such as MnSOD, p27Kip1, and BIM-1. p66Shc downregulation also increases
      proliferating cell nuclear antigen expression and induces cardiomyocyte
      hypertrophy, suggesting that p66Shc exerts an antihypertrophic action in neonatal
      cardiomyocytes. The novel alpha(1)-AR- and ROS-dependent pathway involving p66Shc
      identified in this study is likely to contribute to cardiomyocyte remodeling and
      the evolution of heart failure.

PMID- 19168440
TI  - Oxidized phospholipids induce type VIII collagen expression and vascular smooth
      muscle cell migration.
AB  - Phenotypic switching of vascular smooth muscle cells (VSMCs) is known to play a
      critical role in the development of atherosclerosis. However, the factors present
      within lesions that mediate VSMC phenotypic switching are unclear. Oxidized
      phospholipids (OxPLs), including 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3
      phosphorylcholine (POVPC), are active components of minimally modified low
      density lipoprotein and have been previously shown to induce multiple
      proatherogenic events in endothelial cells and macrophages, but their effects on
      VSMCs have been largely unexplored until recently. We previously showed that
      OxPLs induced phenotypic switching of VSMCs, including suppression of SMC
      differentiation marker genes. The goal of the present studies was to test the
      hypothesis that OxPLs alter extracellular matrix production and VSMC migration.
      Results showed that POVPC activated expression of several extracellular matrix
      proteins in VSMC. POVPC increased expression of type VIII collagen alpha1 chain
      (Col8a1) mRNA in cultured VSMCs and in vivo in rat carotid arteries by 9-fold and
      4-fold, respectively. POVPC-induced activation of Col8a1 gene expression was
      reduced by small interfering RNA-mediated suppression of Kruppel-like factor 4
      (Klf4) and Sp1, and was abolished in Klf4-knockout VSMCs. POVPC increased Klf4
      binding to the Col8a1 gene promoter both in vivo in rat carotid arteries and in
      cultured VSMCs based on chromatin immunoprecipitation assays. Moreover, POVPC
      induced VSMC migration was markedly reduced in Klf4- or type VIII collagen
      knockout VSMCs. Given evidence that OxPLs are present within atherosclerotic
      lesions, it is interesting to suggest that OxPL-induced changes in VSMC phenotype
      may contribute to the pathogenesis of atherosclerosis at least in part through
      changes in extracellular matrix composition.

PMID- 19168441
TI  - Human endothelial cells of the placental barrier efficiently deliver cholesterol
      to the fetal circulation via ABCA1 and ABCG1.
AB  - Although maternal-fetal cholesterol transfer may serve to compensate for
      insufficient fetal cholesterol biosynthesis under pathological conditions, it may
      have detrimental consequences under conditions of maternal hypercholesterolemia
      leading to preatherosclerotic lesion development in fetal aortas. Maternal
      cholesterol may enter fetal circulation by traversing syncytiotrophoblast and
      endothelial layers of the placenta. We hypothesized that endothelial cells (ECs)
      of the fetoplacental vasculature display a high and tightly regulated capacity
      for cholesterol release. Using ECs isolated from human term placenta (HPECs), we
      investigated cholesterol release capacity and examined transporters involved in
      cholesterol efflux pathways controlled by liver-X-receptors (LXRs). HPECs
      demonstrated 2.5-fold higher cholesterol release to lipid-free apolipoprotein
      (apo)A-I than human umbilical vein ECs (HUVECs), whereas both cell types showed
      similar cholesterol efflux to high-density lipoproteins (HDLs). Interestingly,
      treatment of HPECs with LXR activators increased cholesterol efflux to both types
      of acceptors, whereas no such response could be observed for HUVECs. In line with
      enhanced cholesterol efflux, LXR activation in HPECs increased expression of ATP
      binding cassette transporters ABCA1 and ABCG1, while not altering expression of
      ABCG4 and scavenger receptor class B type I (SR-BI). Inhibition of ABCA1 or
      silencing of ABCG1 decreased cholesterol efflux to apoA-I (-70%) and HDL(3) (
      57%), respectively. Immunohistochemistry localized both transporters
      predominantly to the apical membranes of placental ECs in situ. Thus, ECs of
      human term placenta exhibit unique, efficient and LXR-regulated cholesterol
      efflux mechanisms. We propose a sequential pathway mediated by ABCA1 and ABCG1,
      respectively, by which HPECs participate in forming mature HDL in the fetal
      blood.

PMID- 19168442
TI  - Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue
      factor in human endothelial cells.
AB  - Tumor necrosis factor (TNF)-alpha-stimulated human umbilical vein endothelial
      cells express 2 naturally occurring forms of tissue factor (TF), the primary
      initiator of blood coagulation: the soluble alternatively spliced isoform and the
      full-length TF isoform. The regulatory pathways enabling this phenomenon are
      completely unknown. Cdc2-like kinases and DNA topoisomerase I regulate
      alternative splicing via phosphorylation of serine/arginine-rich proteins. In
      this study, we examined effects of serine/arginine-rich protein kinases on TF
      splicing following stimulation with TNF-alpha. Human endothelial cells were
      pretreated with specific inhibitors or small interfering RNAs against Cdc2-like
      kinases and DNA topoisomerase I before stimulation with TNF-alpha. TF levels were
      determined by semiquantitative RT-PCR, real-time PCR, and Western blotting.
      Cellular procoagulant activity was analyzed in a chromogenic TF activity assay.
      All 4 known Cdc2-like kinases forms were expressed in human endothelial cells.
      Selective inhibition of Cdc2-like kinases and DNA topoisomerase I elicited
      distinct changes in TF biosynthesis in TNF-alpha-stimulated endothelial cells,
      which impacted endothelial procoagulant activity. This study is the first to
      demonstrate that serine/arginine-rich protein kinases modulate splicing of TF pre
      mRNA in human endothelial cells and, consequently, endothelial procoagulant
      activity under inflammatory conditions.

PMID- 19168443
TI  - Ultrasound and microbubble-targeted delivery of macromolecules is regulated by
      induction of endocytosis and pore formation.
AB  - Contrast microbubbles in combination with ultrasound (US) are promising vehicles
      for local drug and gene delivery. However, the exact mechanisms behind
      intracellular delivery of therapeutic compounds remain to be resolved. We
      hypothesized that endocytosis and pore formation are involved during US and
      microbubble targeted delivery (UMTD) of therapeutic compounds. Therefore, primary
      endothelial cells were subjected to UMTD of fluorescent dextrans (4.4 to 500 kDa)
      using 1 MHz pulsed US with 0.22-MPa peak-negative pressure, during 30 seconds.
      Fluorescence microscopy showed homogeneous distribution of 4.4- and 70-kDa
      dextrans through the cytosol, and localization of 155- and 500-kDa dextrans in
      distinct vesicles after UMTD. After ATP depletion, reduced uptake of 4.4-kDa
      dextran and no uptake of 500-kDa dextran was observed after UMTD. Independently
      inhibiting clathrin- and caveolae-mediated endocytosis, as well as
      macropinocytosis significantly decreased intracellular delivery of 4.4- to 500
      kDa dextrans. Furthermore, 3D fluorescence microscopy demonstrated dextran
      vesicles (500 kDa) to colocalize with caveolin-1 and especially clathrin.
      Finally, after UMTD of dextran (500 kDa) into rat femoral artery endothelium in
      vivo, dextran molecules were again localized in vesicles that partially
      colocalized with caveolin-1 and clathrin. Together, these data indicated uptake
      of molecules via endocytosis after UMTD. In addition to triggering endocytosis,
      UMTD also evoked transient pore formation, as demonstrated by the influx of
      calcium ions and cellular release of preloaded dextrans after US and microbubble
      exposure. In conclusion, these data demonstrate that endocytosis is a key
      mechanism in UMTD besides transient pore formation, with the contribution of
      endocytosis being dependent on molecular size.

PMID- 19168444
TI  - Rosuvastatin 20 mg restores normal HDL-apoA-I kinetics in type 2 diabetes.
AB  - Catabolism of HDL particles is accelerated in type 2 diabetes, leading to a
      reduction in plasma residence time, which may be detrimental. Rosuvastatin is the
      most powerful statin to reduce LDL-cholesterol, but its effects on HDL metabolism
      in type 2 diabetes remain unknown. We performed a randomized double-blind cross
      over trial of 6-week treatment period with placebo or rosuvastatin 20 mg in eight
      patients with type 2 diabetes. An in vivo kinetic study of HDL-apolipoprotein A-I
      (apoA-I) with (13)C leucine was performed at the end of each treatment period.
      Moreover, a similar kinetic study was carried out in eight nondiabetic
      normolipidemic controls. Rosuvastatin significantly reduced plasma LDL
      cholesterol (-51%), triglycerides (TGs) (-38%), and HDL-TG (-23%). HDL-apoA-I
      fractional catabolic rate (FCR) was decreased by rosuvastatin (0.25 +/- 0.06 vs.
      0.32 +/- 0.07 pool/day, P = 0.011), leading to an increase in plasma HDL-apoA-I
      residence time (4.21 +/- 1.02 vs. 3.30 +/- 0.73 day, P = 0.011). Treatment with
      rosuvastatin was associated with a concomitant reduction of HDL-apoA-I production
      rate. The decrease in HDL-apoA-I FCR, induced by rosuvastatin, was correlated
      with the reduction of plasma TGs and HDL-TG. HDL apoA-I FCR and production rate
      values in diabetic patients on rosuvastatin were not different from those found
      in controls. Rosuvastatin is responsible for a 22% reduction of HDL-apoA-I FCR
      and restores to normal the increased HDL turnover observed in type 2 diabetes.
      These kinetic modifications may have beneficial effects by increasing HDL plasma
      residence time.

PMID- 19168445
TI  - Effect of androgen suppression compared with androgen receptor blockade on
      arterial stiffness in men with prostate cancer.
AB  - Endogenous testosterone and estradiol are thought to be cardio-protective in men.
      We wanted to determine the effects of 2 different anti-androgen therapies on
      arterial stiffness as one suppresses (goserelin--a gonadotrophin-releasing
      hormone analog) while the other increases (bicalutamide--an androgen receptor
      blocker) both testosterone and estradiol. We conducted a randomized trial on 43
      men (mean age, 71.2 +/- 6.2 years) with localized prostate cancer. They received
      either goserelin or bicalutamide for 24 weeks. Carotid-femoral (C-F) and carotid
      radial (C-R) pulse wave velocities (PWVs) were measured. Twenty age- and disease
      matched men with prostate cancer on no active treatment were studied in a similar
      manner. After 12 weeks of goserelin, radial artery PWV increased significantly
      from baseline and a nonsignificant increase was observed in femoral PWV (change
      from baseline radial: +1.4 m/s, P = .002, femoral: +0.9 m/s, P = .127) Both PWV
      measures increased significantly with bicalutamide (change from baseline radial:
      +0.8, femoral: +0.9 m/s, P <or= .049). PWV increased further after 24 weeks with
      goserelin (change from baseline radial: +1.7, femoral: +1.3 m/s, P <or= .049 for
      both) but not bicalutamide (change from baseline radial: +0.4, femoral: +0.4 m/s,
      P not significant [NS]); however, comparison of changes between the 2 drugs were
      not significantly different at either 12 or 24 weeks (P >or= .967 at 12 weeks and
      P >or= .07 at 24 weeks). The untreated men studied in parallel showed no changes
      at 12 or 24 weeks in either PWV measure. Anti-androgen treatment in men might
      increase large artery stiffness, an adverse cardiovascular risk factor; however,
      the effect was not maintained with testosterone receptor blockade, in the longer
      term, but tended to be sustained with suppression therapy. This could relate to
      the different sex hormone effects of the 2 therapies.

PMID- 19168446
TI  - Semen collection and ejaculate characteristics in the Indo-Pacific bottlenose
      dolphin (Tursiops aduncus).
AB  - The testes of sexually mature dolphins produce large quantities of sperm. Sperm
      are expelled in copious amounts of seminal fluid through repeated ejaculations
      that can occur within a short period of time. There is currently a lack of detail
      about the methodology of sequential ejaculate collection in dolphins and how the
      traits of individual ejaculates affect the assessment of reproductive capacity.
      The objectives of this study were to obtain series of ejaculates from 3 dolphins
      by following a well-defined collection protocol and then to characterize
      individual ejaculates. Semen was collected weekly for 1 year from 3 sexually
      mature Tursiops aduncus. The end of a collection session was marked by a lack of
      semen, in spite of effort, or micturition. Individual ejaculates were analyzed
      for volume, pH, and sperm concentration, count, motility, and viability following
      methods previously described for dolphin semen. The first ejaculate was typically
      higher in volume and sperm count but lower in sperm concentration, motility, and
      viability. The concentration of the second ejaculate was generally the highest.
      Sperm motility and viability of the second and subsequent ejaculates in a series
      were good (ie, >80%). Collection of the first ejaculate only can lead to
      underestimation of reproductive capacity. Sperm output fluctuated erratically
      from week to week, so it was difficult to assess any seasonal pattern. Results
      provide information for further investigation of male dolphin reproductive
      patterns and any effect of collection frequency on ejaculate characteristics.

PMID- 19168447
TI  - Thyroid diseases and erectile dysfunction.

PMID- 19168448
TI  - Effect of egg yolk on cryopreservation of rhesus monkey ejaculated and epididymal
      sperm.
AB  - Sperm cryopreservation in rhesus monkeys has not been successful when applied in
      standard, intravaginal artificial insemination; thus, there is a need for
      substantial improvement in current cryopreservation protocols. The present study
      was part of our systematic approach to optimize the cryopreservation procedure.
      Specifically, we tested whether modification of the concentration of egg yolk,
      the dilution method, and the time delay between ejaculation and adding egg yolk
      would result in significant improvement of postthaw motility for ejaculated
      sperm. We also tested the effects of presence and absence of egg yolk on
      cryopreservation of ejaculated and epididymal sperm. Our findings indicated that
      the concentration of egg yolk (2%-50%, vol/vol), the dilution method, and the
      delay (1-5 hours) in addition of egg yolk had no significant effect on postthaw
      motility of ejaculated rhesus monkey sperm. The presence of egg yolk yielded
      significantly higher motility after thawing than samples without egg yolk for
      ejaculated and epididymal sperm. The present study suggests that as long as egg
      yolk is present in the extender, details such as the amount of egg yolk, as well
      as when and how to add the egg yolk, have little impact on the ultimate freezing
      outcomes for ejaculated rhesus monkey sperm. We also discuss the possible
      mechanism of the protective role of egg yolk in sperm cryopreservation.

PMID- 19168449
TI  - Postmortem sperm retrieval: the Canadian perspective.
AB  - Postmortem sperm retrieval has been used worldwide. Following retrieval, sperm
      can then be used (usually by the surviving partner) to produce a child related to
      the now-deceased male. This paper describes a request for postmortem sperm
      retrieval made by the family of a man who had suffered trauma leading to his
      death. The man had not given written consent for the retrieval and use of his
      sperm before his accidental death. The case illustrates some of the complex
      ethical and legal issues occurring in Canada and describes the new Canadian
      regulations, which prohibit postmortem sperm retrieval unless explicit written
      consent has been provided by the deceased.

PMID- 19168450
TI  - Single-nucleotide polymorphisms of the PRDM9 (MEISETZ) gene in patients with
      nonobstructive azoospermia.
AB  - To investigate the possible association between variations in the PRDM9 (MEISETZ)
      gene and impaired spermatogenesis in humans, we screened for mutations in the
      human PRDM9 gene using DNA from 217 sterile male patients and 162 proven fertile
      male volunteers. Two single-nucleotide polymorphisms (SNPs), 17353G>T (Gly433Val)
      and 18109C>G (Thr685Arg), were identified, as well as an intronic SNP, 15549G>T.
      These SNPs were identified in the heterozygous state in separate patients who
      demonstrated azoospermia. Neither variant was identified in fertile subjects. Our
      results suggest that mutations in PRDM9 may cause idiopathic infertility in human
      males.

PMID- 19168451
TI  - Length of androgen receptor-CAG repeats in fertile and infertile Egyptian men.
AB  - Androgens play key roles in spermatogenesis, and they exert their effect via the
      androgen receptor (AR). The AR gene has a repetitive DNA sequence in exon 1 that
      encodes a polyglutamine tract. Instability in the glutamine (CAG) repeat unit
      length is polymorphic across ethnic groups. Previous studies of the relationship
      between the repeat unit length and male infertility have been contradictory. To
      establish the range of wild-type alleles in Egyptian men, we determined the range
      of repeat lengths in a population of normally fertile, ethnically selected
      Egyptian men. We also investigated the association between trinucleotide repeat
      length within the AR gene and male factor infertility in a population of
      ethnically selected Egyptian infertile men, who were compared with fertile,
      ethnic group-matched and age-matched controls. The study included 129 clinically
      selected infertile Egyptian men who were scheduled for intracytoplasmic sperm
      injection and 52 ethnically matched fertile controls. The experimental population
      was grouped according to sperm counts ranging from nonobstructive azoospermia to
      normozoospermia. The CAG repeat N-terminal domain region of the AR gene was
      amplified in peripheral blood DNA, and allele size was determined by fragment
      analysis. Allele size and single-nucleotide polymorphism and mutation rates were
      determined by sequencing individual amplified alleles. The mean CAG repeat length
      in the azoospermia group was 18.55 +/- 2.0; in the severe oligozoospermia group
      it was 18.21 +/- 3.42; in the oligozoospermia group it was 18.27 +/- 2.93; and in
      the infertile with normal sperm count group it was 17.72 +/- 2.0. In the control
      group, the mean CAG repeat length was 18.18 +/- 3.63. No significant correlation
      was found between CAG repeat length and the risk of male factor infertility in an
      ethnically defined population of Egyptian men. However, a significant and
      positive correlation between CAG repeat length and serum testosterone
      concentration was demonstrated. This suggests the involvement of epigenetic
      regulation linked to this region.

PMID- 19168452
TI  - Synaptic plasticity, dopamine and Parkinson's disease: one step ahead.

PMID- 19168453
TI  - Doctors who write literature may be considered to have crossed from science to
      the humanities obtaining release from the rigid constraints of logic, experiment
      and fact, and gaining the freedoms of imagination, metaphor and fiction.

PMID- 19168454
TI  - Childhood brain insult: can age at insult help us predict outcome?
AB  - Until recently, the impact of early brain insult (EBI) has been considered to be
      less significant than for later brain injuries, consistent with the notion that
      the young brain is more flexible and able to reorganize in the context of brain
      insult. This study aimed to evaluate this notion by comparing cognitive and
      behavioural outcomes for children sustaining EBI at different times from
      gestation to late childhood. Children with focal brain insults were categorized
      according to timing of brain insult, represented by six developmental periods:
      (i) Congenital (n = 38): EBI: first-second trimester; (ii) Perinatal (n = 33);
      EBI: third trimester to 1 month post-natal; (iii) Infancy (n = 23): EBI: 2 months
      2 years post-birth; (iv) Preschool (n = 19): EBI: 3-6 years; (v) Middle Childhood
      (n = 31): EBI: 7-9 years; and (vi) Late Childhood (n = 19): EBI: after age 10.
      Groups were similar with respect to injury and demographic factors. Children were
      assessed for intelligence, academic ability, everyday executive function and
      behaviour. Results showed that children with EBI were at increased risk for
      impairment in all domains assessed. Furthermore, children sustaining EBI before
      age 2 years recorded global and significant cognitive deficits, while children
      with later EBI performed closer to normal expectations, suggesting a linear
      association between age at insult and outcome. In contrast, for behaviour,
      children with EBI from 7 to 9 years performed worse than those with EBI from 3 to
      6 years, and more like those with younger insults, suggesting that not all
      functions share the same pattern of vulnerability with respect to age at insult.

PMID- 19168455
TI  - Four TFL1/CEN-like genes on distinct linkage groups show different expression
      patterns to regulate vegetative and reproductive development in apple (Malus x
      domestica Borkh.).
AB  - Recent molecular analyses in several plant species revealed that TERMINAL FLOWER1
      (TFL1) and CENTRORADIALIS (CEN) homologs are involved in regulating the flowering
      time and/or maintaining the inflorescence meristem. In apple (Malusxdomestica
      Borkh.), four TFL1/CEN-like genes, MdTFL1, MdTFL1a, MdCENa and MdCENb, were found
      and mapped by a similar position on putatively homoeologous linkage groups. Apple
      TFL1/CEN-like genes functioned equivalently to TFL1 when expressed constitutively
      in transgenic Arabidopsis plants, suggesting that they have a potential to
      complement the TFL1 function. Because MdTFL1 and MdTFL1a were expressed in the
      vegetative tissues in both the adult and juvenile phases, they could function
      redundantly as a flowering repressor and a regulator of vegetative meristem
      identity. On the other hand, MdCENa was mainly expressed in fruit receptacles,
      cultured tissues and roots, suggesting that it is involved in the development of
      proliferating tissues but not in the control of the transition from the juvenile
      to the adult phase. In contrast, MdCENb was silenced in most organs probably due
      to gene duplication by the polyploid origin of apple. The expression patterns of
      MdTFL1 and MdCENa in apple were also supported by the heterologous expression of
      beta-glucuronidase fused with their promoter regions in transgenic Arabidopsis.
      Our results suggest that functional divergence of the roles in the regulation of
      vegetative meristem identity may have occurred among four TFL1/CEN-like genes
      during evolution in apple.

PMID- 19168456
TI  - Chlorogenic acid facilitates root hair formation in lettuce seedlings.
AB  - Root hairs, which arise from root epidermal cells, are tubular structures that
      increase the efficiency of water absorption and nutrient uptake. A low pH (pH 4)
      medium induced root hair formation in lettuce (Lactuca sativa L.) seedlings, and
      the decapitation of shoots inhibited root hair formation. The addition of shoot
      extract to the medium restored root hair formation in the decapitated lettuce
      seedlings. These results suggest that factors essential to the formation of root
      hairs may be present in the shoot. We purified one factor from the shoot that
      facilitates root hair formation. This factor was identified as chlorogenic acid
      (CGA), a common polyphenol in higher plants. The presence of exogenous CGA in the
      medium induced root hair formation in decapitated lettuce seedlings at pH 4.0 and
      in intact lettuce seedlings at pH 6.0. The optimum concentration of CGA for root
      hair formation was identified as 10(-5) M. Decapitation of the shoots reduced the
      CGA content in the roots to approximately one-third that in intact plants.
      Application of the CGA biosynthesis inhibitor L-alpha-aminooxy-beta
      phenylpropionic acid (AOPP, 10(-6) M) to intact seedlings grown at pH 4.0 reduced
      both the CGA content of the roots and the total amount of root hairs. The
      addition of exogenous CGA restored root hair formation in intact seedlings
      treated with AOPP. These results suggest that CGA is essential for root hair
      formation in lettuce seedlings.

PMID- 19168457
TI  - VAJ/GFA1/CLO is involved in the directional control of floral organ growth.
AB  - Flowers assume variant forms of reproductive structures, a phenomenon which may
      be partially due to the diversity among species in the shape and size of floral
      organs. However, the organ size and shape of flowers usually remain constant
      within a species when grown under the same environmental conditions. The
      molecular and genetic mechanisms that control organ size and shape are largely
      unknown. We isolated an Arabidopsis mutant, vajra-1 (vaj-1), exhibiting defects
      in the regulation of floral organ size and shape. In vaj-1, alterations in the
      size and shape of floral organs were caused by changes in both cell size and cell
      number. The vaj-1 mutation also affected the number of floral organs. In vaj-1, a
      mutation was found in GAMETOPHYTIC FACTOR 1 (GFA1)/CLOTHO (CLO), recently shown
      to be required for female gametophyte development. The VAJ/GFA1/CLO gene encodes
      a translational elongation factor-2 (EF-2) family protein, of which the human U5
      116 kD and yeast Snu114p counterparts are U5 small nuclear ribonucleoprotein
      (snRNP)-specific proteins. A transient expression assay using Arabidopsis
      protoplasts revealed that VAJ protein co-localized with SC35, a serine/arginine
      rich (SR) protein involved in pre-mRNA splicing. Our results showed that
      VAJ/GFA1/CLO has a novel role in the directional control of floral organ growth
      in Arabidopsis, possibly acting through pre-mRNA splicing.

PMID- 19168458
TI  - Introduction to this issue: the seven ages of man . . . (or woman).

PMID- 19168459
TI  - Alcohol consumption behaviours and social mobility in men and women of the
      Midspan Family study.
AB  - AIMS: The aim of this study was to investigate relationships between alcohol
      consumption and social mobility in a cohort study in Scotland. METHODS: 1040 sons
      and 1298 daughters aged 30-59 from 1477 families reported their alcohol
      consumption from which was derived: weekly units (1 UK unit being 8 g ethanol),
      exceeding daily or weekly limits, binge drinking and consuming alcohol on 5+ days
      per week. Own and father's social class were available enabling social mobility
      to be investigated. RESULTS: More downwardly mobile men exceeded the weekly
      limit, the daily limit, were defined as binge drinkers and drank the most units
      per week of the four social mobility groups. Stable non-manual women were more
      likely to consume alcohol on 5+ days a week but very few were binge drinkers.
      Stable non-manual and upwardly mobile men and women were more likely to drink
      wine, and downwardly mobile men to drink beer. CONCLUSIONS: Downward mobility was
      associated with less favourable alcohol behaviours, especially in men. Wine
      consumption was more closely related to the social mobility groups than beer and
      spirits consumption. Drinking patterns could both influence and be influenced by
      social mobility.

PMID- 19168460
TI  - Alcohol poisoning in Belarus: a comparison of urban-rural trends, 1990-2005.
AB  - AIM: The aim of this study was to investigate the occurrence of alcohol poisoning
      in urban and rural regions of Belarus in the post-Soviet period. METHODS: All-age
      male and female alcohol-poisoning mortality and population data were obtained for
      the years 1990, 1995, 2000 and 2005 for urban and rural regions of Belarus. These
      data were subsequently recalculated into three age categories and directly
      standardized. Poisson regression models were used to assess relative changes in
      rural-urban alcohol-poisoning rates across time. RESULTS: Although extremely high
      in comparative terms in 1990, alcohol-poisoning rates had nevertheless risen
      considerably amongst men and women in all age groups in both urban and rural
      regions by 2005. In rural regions, the rise was continuous while amongst the
      urban population a small reduction was recorded in 2000 after a comparatively
      larger rise in 1995. By 2005, although alcohol-poisoning rates were significantly
      higher amongst rural men and women, the levels of acute alcohol mortality were
      nevertheless extremely high in nearly every age group in both urban and rural
      locations. CONCLUSIONS: It is probable that both the level and pattern of alcohol
      consumption in conjunction with the increasing use of illegal alcohol underlie
      the extremely high alcohol-poisoning rates in contemporary Belarus, and the
      growing rural-urban divergence in alcohol-poisoning mortality observed in recent
      years. Immediate action is now required to improve the poor social and economic
      conditions underpinning extreme levels of acute alcohol mortality, as well as to
      increase the provision of alcohol treatment services, especially in rural areas.

PMID- 19168461
TI  - Could atrial natriuretic peptide be a useful drug therapy for high-risk patients
      after cardiac surgery?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether atrial natriuretic peptide (ANP) or
      brain natriuretic peptide (BNP) could be a useful alternative diuretic for
      patients post cardiac surgery. Altogether more than 250 papers were found using
      the reported search, of which eight RCTs represented the best evidence to answer
      the clinical question. The authors, journal, date and country of publication,
      patient group studied, study type, relevant outcomes and results of these papers
      are tabulated. We conclude that the RCTs consistently showed a diuretic effect
      with increased creatinine clearance, and increased urine volume and reduced usage
      of conventional diuretics. Lower urea and creatinine levels were also found
      postoperatively and also reduced decreases in glomerular filtration rate compared
      to placebo, both in studies of patients with preoperatively normal renal function
      and those who had impaired function. In addition, two studies found a reduction
      in the incidence of AF, and renin/aldosterone levels were lower. The NAPA trial
      of 272 CABG patients with LV dysfunction was the only study to show a shorter ICU
      stay and reduced early mortality with nesiritide compared to placebo.

PMID- 19168462
TI  - Fatal complications of pacemaker and implantable cardioverter-defibrillator
      implantation: medical malpractice?
AB  - OBJECTIVES: Pacemaker implantation has become a routine procedure in modern
      cardiology, and implantable cardioverter-defibrillators are implanted with rising
      frequency. Although fatal complications are relatively rare, they may give rise
      to malpractice lawsuits against medical personnel. The objective was to identify
      fatal complications after pacemaker and implantable cardioverter-defibrillators
      implantation and to evaluate the legal consequences in alleged malpractice cases.
      METHODS: Retrospective analysis of all 27,730 autopsy cases performed at the
      Institute of Legal Medicine, Hamburg, Germany, between January 1983 and June
      2007. Study cases were identified using the keywords 'cardiac death',
      'malpractice', 'complications', 'pacemaker' and 'implantable cardioverter
      defibrillator'. RESULTS: Eleven pacemaker-related and four implantable
      cardioverter-defibrillator-related fatalities where lawsuits had been filed were
      identified. A causal connection between the procedure and fatal outcome was
      confirmed by autopsy in six cases. Malpractice or violation of the rules of good
      medical practice could be excluded in all cases. All inquiries were abandoned.
      CONCLUSION: Fatal complications after pacemaker and implantable cardioverter
      defibrillator implantation attributable to medical malpractice are extremely
      rare. The study illustrates the importance of a medico-legal autopsy in alleged
      fatal malpractice cases.

PMID- 19168463
TI  - Chronic kidney disease after heart transplantation.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a complication of heart
      transplantation related to calcineurin inhibitor nephrotoxicity. However, it is
      unclear whether early ciclosporin (CsA) exposure influences CKD in the long term.
      METHODS: We analysed risk factors for CKD in 352 patients who underwent
      orthotopic heart transplantation (1995-2005). In 2000, we reduced our target CsA
      levels in the first year after transplantation. RESULTS: Actuarial patient
      survival was 79% at 1 year and 62% at 10 years. Estimated median glomerular
      filtration rate (eGFR) by the four-variable Modification of Diet in Renal Disease
      formula was 64 ml/min/1.73 m2 before transplantation, inter-quartile range (IQR)
      54-78. After transplantation, the eGFR was 48 (IQR 37-61) at Year 1, and 41(35
      57) at Year 10. The cumulative probability of eGFR <45 ml/min/1.73 m2 was 45% at
      Year 1, 71% at Year 5 and 83% at Year 10. A multivariable logistic regression
      model was constructed for the development of eGFR <45 ml/min/1.73 m2 by 3 years.
      The risk factors were post-operative renal replacement therapy for acute renal
      failure (ARF), P < 0.001; pretransplant diabetes, P = 0.005; increasing recipient
      age, P < 0.001; female recipient, P = 0.029; female donor, P = 0.04, but not CsA
      regimen. The cumulative probability of developing stage 5 CKD (eGFR <15) was 3%
      at Year 5 and 12% at Year 10. Although lower ciclosporin initial levels were
      associated with less renal dysfunction at Year 1 (P = 0.008), there was no
      significant effect by Year 3 (P = 0.7). CONCLUSION: The incidence of CKD
      increased with time and was not influenced by the CsA regimen. Some risk factors
      are not modifiable but measures to reduce the incidence of post-operative ARF may
      help to reduce CKD.

PMID- 19168464
TI  - Aortic, celiac axis, and superior mesenteric artery thrombosis associated with
      sigmoid colon adenocarcinoma and hypercoagulable state.
AB  - A patient with sigmoid colon adenocarcinoma and hypercoagulable state developed
      acute visceral ischemia secondary to thrombus involving the suprarenal aorta,
      celiac axis and superior mesenteric artery. A large, laminated fibrin thrombus
      was removed via supraceliac aortotomy. Attempts to clear thrombus from branches
      of the celiac axis and superior mesenteric artery by open and catheter-based
      techniques were of limited success. Extensive visceral infarction ensued and the
      patient died.

PMID- 19168465
TI  - Self-assessment of the training of vascular fellows: survey results of 219
      vascular fellows from 2004 through 2007.
AB  - Introduction. In an attempt to identify the concerns of vascular fellows
      regarding their training in vascular surgery, we conducted a survey consisting of
      22 questions at an annual national meeting from 2004 to 2007. Methods. The
      fellows were asked to assess various aspects of their training as excellent,
      satisfactory, or mixed. Results. 76% were satisfied with their endovascular
      experience during their fellowship while 82% were satisfied with their experience
      with open cases. The distribution of non-learning cases was felt to be excellent,
      satisfactory, or required some or much improvement in: 45%, 44%, 8%, and 2%
      respectively. However, only 61% felt that their vascular laboratory experience
      was excellent or satisfactory. Only 36% actually performed the vascular duplex
      exam, and only 49% felt that they would feel comfortable in managing a vascular
      laboratory. Conclusions. The results of this Survey suggest that several
      significant issues are reflected in the minds of vascular trainees.

PMID- 19168466
TI  - Sustained postoperative face-down positioning is unnecessary for successful
      macular hole surgery.
AB  - AIM: To determine the rate of successful macular hole closure with 1-day
      postoperative prone positioning METHODS: Multicentre review of all consecutive
      cases of stage 3 and 4 macular hole surgery performed during a 15-month period
      employing 1-day postoperative face-down positioning regimen. Cataract surgery was
      not routinely combined with macular hole surgery. Internal limiting membrane
      peeling was employed in all but seven eyes. Either SF6 or C3F8 gas tamponade was
      used. The primary outcome assessed was the rate of hole closure. RESULTS: 56 eyes
      of 53 patients were identified. 79% of eyes had stage 3 macular holes, and 39 of
      56 (70%) eyes were phakic at the time of surgery. The mean preoperative logMAR
      vision was 0.74 (approximately 20/100 Snellen) and mean postoperative logMAR
      vision was 0.41 ( approximately 20/50 Snellen) with a mean follow-up period of
      5.2 months. Macular hole closure was achieved in 52 eyes (93%) with one
      operation. CONCLUSION: Sustained postoperative face-down positioning may not be
      necessary for successful macular hole closure, since 93% of eyes achieved hole
      closure with prone positioning for only 1 day.

PMID- 19168467
TI  - Improving refractive outcomes at extreme axial lengths with the IOLMaster: the
      optical axial length and keratometric transformation.
AB  - AIMS: To optimise the relationship between the actual and predicted refractive
      outcomes following phacoemulsification and axial length of the eye. Four
      intraocular lens (IOL) power calculation formulae were compared: SKR-T, Holladay
      I, Hoffer-Q and Haigis. Optical axial length transformation based on the original
      calibration of the IOLMaster was tested to improve the predictability of
      outcomes. METHODS: The refractive outcomes of 155 eyes of 120 patients using the
      IOLMaster were reviewed following phacoemulsification. After optimising the IOL
      constants, the prediction error (PE; achieved spherical equivalent - calculated
      spherical equivalent) of each of the formulae was calculated for each eye and
      then correlated to the axial length of the eye with and without the optical
      transformation. Keratometry measurements of the IOLMaster were tested by
      transforming to that of standard autokeratometry. This was validated in a second
      group of 90 eyes. RESULTS: The PE of all but the Haigis triple optimised formula
      were found to be positively correlated to the axial length. The optical and
      keratometric transformation statistically significantly reduced this correlation,
      leading to fewer PE at all axial lengths. PE per millimetre axial length was 0.06
      D/mm (SRK-T), 0.16 D/mm (Hoffer-Q), 0.14 D/mm (Holladay I), 0.11 D/mm (Haigis
      single) and -0.02 D/mm (Haigis triple). Following transformation, best case PE
      was reduced to -0.01 D/mm (SRK-T), 0.08 D/mm (Hoffer-Q), 0.01 D/mm (Holladay I),
      0.01 D/mm (Haigis single) and -0.01 D/mm (Haigis triple). CONCLUSION:
      Transforming the IOLMaster measurement into the optical axial length while
      compensating for its keratometry measurement was able to improve the
      predictability of outcomes at extreme axial lengths without further modification
      to the standard IOL formulae.

PMID- 19168468
TI  - Measurement of total blood flow in the normal human retina using Doppler Fourier
      domain optical coherence tomography.
AB  - AIM: To measure total retinal blood flow in normal human eyes using Doppler
      Fourier-domain optical coherence tomography (FD-OCT). METHODS: 10 normal people
      aged 35 to 69 years were measured for the right eye using Doppler FD-OCT. Double
      circular scans around the optic nerve heads were used. Four pairs of circular
      scans that transected all retinal branch vessels were completed in 2 s. Total
      retinal blood flow was obtained by summing the flows in the branch veins.
      Measurements from the eight scans were averaged. Veins with diameters >33 microm
      were taken into account. RESULTS: Total retinal blood flow could be measured in
      eight of 10 subjects: mean (SD) = 45.6 (3.8) microl/min (range 40.8 to 52.9
      microl/min). The coefficient of variation for repeated measurements was 10.5%.
      Measured vein diameters ranged from 33.3 to 155.4 mum. The averaged flow speed
      was 19.3 (2.9) mm/s, which did not correlate with vessel diameter. There was no
      significant difference between flows in the superior and inferior retinal
      hemispheres. CONCLUSIONS: Double circular scanning using Doppler FD-OCT is a
      rapid and reproducible method to measure total retinal blood flow. These flow
      values are within the range previously established by laser Doppler flowmetry.

PMID- 19168469
TI  - Epstein-Barr virus is associated with grey matter atrophy in multiple sclerosis.
AB  - OBJECTIVE: The aim of the study was to determine whether the presence of anti
      Epstein-Barr virus (EBV) antibodies is associated with MRI measures of brain
      injury and neurodegeneration in patients with multiple sclerosis (MS). METHODS:
      135 patients with MS (86 women, 49 men) underwent brain MRI and testing for
      antibodies against EBV. MRI measurements included gadolinium enhancing lesion
      volume, T1 and T2 lesion volumes and fractions of whole brain parenchyma (BPF),
      white matter and grey matter (GMF). The anti-EBV panel included anti-EBV early
      antigen IgG, anti-EBV nuclear antigen IgG and anti-EBV viral capsid antigen (VCA)
      IgG levels. The relationships between antibody levels and MRI measurements were
      assessed in regression analysis. Repeat measurements of anti-EBV VCA IgG and MRI
      measures were available for a subset of 50 patients after a mean follow-up of 3.1
      years. RESULTS: GMF (R(2) = 0.24 for overall model, p = 0.002) and BPF (R(2) =
      0.39 for overall model, p<0.001) showed negative associations with anti-EBV-VCA
      IgG levels. A greater decline in BPF over 3 years was significantly associated
      with increased 3 years prior time point anti-EBV VCA IgG levels (p<0.001).
      CONCLUSIONS: The results suggest that the presence of anti-EBV antibodies is
      associated with MRI markers of GM atrophy in MS and with increased loss of brain
      volume over 3 years.

PMID- 19168470
TI  - Controversies in familial hypercholesterolaemia: recommendations of the NICE
      Guideline Development Group for the identification and management of familial
      hypercholesterolaemia.

PMID- 19168472
TI  - Erythropoietin treatment in patients with chronic heart failure: a meta-analysis.
AB  - BACKGROUND: Anaemia is common in patients with chronic heart failure (HF), and
      erythropoiesis stimulating proteins (ESPs) are frequently used for its treatment.
      However, recent studies in patients with malignancies and renal failure have
      raised concerns about the safety of these agents. OBJECTIVE: To determine whether
      treatment of anaemic patients with chronic HF with ESPs is associated with an
      effect on morbidity and mortality. DATA SOURCES: A systematic literature search
      in Medline, the Cochrane Controlled Trials Register Database and
      ClinicalTrials.gov through July 2008 was performed. STUDY SELECTION: Randomised
      clinical trials comparing the effect of ESP treatment with placebo or usual care
      in anaemic patients with HF were included. RESULTS: Seven randomised controlled
      trials were identified that enrolled 650 patients, of whom 363 were treated with
      ESPs and 287 with placebo. ESP treatment had a significantly lower risk of HF
      hospitalisation (risk ratio (RR) = 0.59; 95% CI 0.41 to 0.86; p = 0.006).There
      was no significant difference in the mortality risk between the two groups (RR =
      0.69; 95% CI 0.39 to 1.23; p = 0.21). No significant differences were observed in
      the occurrence of hypertension or venous thrombosis. CONCLUSIONS: In chronic HF,
      treatment with ESPs is not associated with a higher mortality rate or more
      adverse events, whereas a beneficial effect on HF hospitalisation is seen. These
      outcomes are in contrast with studies in cancer and kidney disease, and support a
      large phase III morbidity and mortality trial of anaemia correction in patients
      with chronic HF.

PMID- 19168473
TI  - Do cardiologists and cardiac surgeons need ethics? Achieving happiness for a drug
      user with endocarditis.
AB  - Ethical dilemmas are commonplace in clinical cardiology. There has been a recent
      focus on ethical behaviour of cardiologists and debate about resource allocation
      and cost-effectiveness of new technologies. The case of an intravenous drug
      addict, with native aortic valve endocarditis complicated by a cerebral abscess
      and severe aortic regurgitation, is presented to illustrate some common ethical
      and moral dilemmas. The predominant theories in medical ethics, including the
      "Four-Principles Approach," is discussed, and a model to translate these ethical
      theories into a clinical decision-making tool is presented.

PMID- 19168474
TI  - Early increase of carotid intima-media thickness in children with parental
      history of premature myocardial infarction.
AB  - BACKGROUND/OBJECTIVE: Increased carotid intima-media thickness (IMT) is an early
      manifestation of atherosclerosis. Our group has previously demonstrated that a
      parental history of premature myocardial infarction (PHPMI) is associated with an
      increase in carotid IMT in children-adolescents (mean age 13 years) and young
      adults (mean age 24 years). The aim of the present study was to evaluate if
      carotid structural changes are detectable in young children with PHPMI. METHODS:
      26 healthy children (9 males and 17 females; 5-12 years, mean age 9.1 (2.5)
      years) with PHPMI and 26 age-matched (plus or minus 1 year), sex-matched and body
      mass index-matched (BMI; plus or minus 20%) control subjects were enrolled in the
      study. They underwent high resolution B-mode ultrasonographic evaluation of
      common carotid artery IMT. Lipid profile, resting blood pressure and BMI were
      also evaluated. RESULTS: Compared to controls, subjects with PHPMI had increased
      IMT of common carotid arteries (mean of combined sites: 0.444 (0.076) mm versus
      0.382 (0.062) mm in controls, p = 0.001). Offspring of coronary patients showed
      an unfavourable lipid profile compared to controls; however, the association
      between a PHPMI and carotid IMT was independent of lipids, apolipoproteins and
      other traditional risk factors. CONCLUSIONS: Vascular structural changes are
      detectable in subjects with PHPMI at a young age and occur independently of
      several traditional cardiovascular risk factors.

PMID- 19168475
TI  - Impact of parental home smoking policies on policy choices of independently
      living young adults.
AB  - OBJECTIVE: To determine whether adolescents living in parental homes where
      smoking is banned are more likely to move into smoke-free living quarters when
      they leave home. METHODS: We analysed data on 693 youths from a 4-year, three
      wave prospective study of a representative sample of Massachusetts adolescents
      (aged 12-17). All youths resided in independent living quarters at follow-up. The
      primary outcome was presence of a smoking ban in the living quarters at follow
      up. The primary predictor was presence of a household smoking ban in the parental
      home, assessed 2 years before the outcome. Generalised linear mixed effects
      models examined the effect of a parental household smoking ban on the odds of
      moving into smoke-free living quarters at follow-up overall and stratified by
      smoking status at follow-up. RESULTS: Youths leaving home had much higher odds of
      moving to smoke-free living quarters if their parental household had had a
      smoking ban (odds ratio (OR) = 12.70, 95% CI, 6.19 to 26.04). Other independent
      predictors included moving into a school or college residence (OR = 3.88, 95% CI
      1.87 to 8.05), and not living with smokers at follow-up (OR = 3.91, 95% CI 1.93
      to 7.92). CONCLUSIONS: A household smoking ban in the parental home appears to
      lead youths to prefer smoke-free living quarters once they leave home.

PMID- 19168476
TI  - Quitting cigarettes completely or switching to smokeless tobacco: do US data
      replicate the Swedish results?
AB  - BACKGROUND: Swedish male smokers are more likely than female smokers to switch to
      smokeless tobacco (snus) and males' smoking cessation rate is higher than that of
      females. These results have fuelled international debate over promoting smokeless
      tobacco for harm reduction. This study examines whether similar results emerge in
      the United States, one of few other western countries where smokeless tobacco has
      long been widely available. METHODS: US DATA SOURCE: national sample in Tobacco
      Use Supplement to Current Population Survey, 2002, with 1-year follow-up in 2003.
      Analyses included adult self-respondents in this longitudinal sample (n =
      15,056). Population-weighted rates of quitting smoking and switching to smokeless
      tobacco were computed for the 1-year period. RESULTS: Among US men, few current
      smokers switched to smokeless tobacco (0.3% in 12 months). Few former smokers
      turned to smokeless tobacco (1.7%). Switching between cigarettes and smokeless
      tobacco, infrequent among current tobacco users (<4%), was more often from
      smokeless to smoking. Men quit smokeless tobacco at three times the rate of
      quitting cigarettes (38.8% vs 11.6%, p<0.001). Overall, US men have no advantage
      over women in quitting smoking (11.7% vs 12.4%, p = 0.65), even though men are
      far likelier to use smokeless tobacco. CONCLUSION: The Swedish results are not
      replicated in the United States. Both male and female US smokers appear to have
      higher quit rates for smoking than have their Swedish counterparts, despite
      greater use of smokeless tobacco in Sweden. Promoting smokeless tobacco for harm
      reduction in countries with ongoing tobacco control programmes may not result in
      any positive population effect on smoking cessation.

PMID- 19168478
TI  - Doing the unthinkable (and saving millions of lives).

PMID- 19168479
TI  - The case against tobacco prohibition.

PMID- 19168482
TI  - 'Our' tobacco industry 'death-lihood' up in smoke? Don't dare dream it!

PMID- 19168483
TI  - Theoretically an option, but an enforcement nightmare.

PMID- 19168484
TI  - Marginalising tobacco control advocates.

PMID- 19168485
TI  - World: health triumphs at COP3.

PMID- 19168489
TI  - Tobacco advertising on the street in Kunming, China.

PMID- 19168490
TI  - Smoker-free workplace policies: developing a model of public health consequences
      of workplace policies barring employment to smokers.
AB  - A marked shift in tobacco-related workplace health promotion intervention
      involves the adoption of policies barring employment to smokers. We discuss the
      potential public health consequences of these policies on those affected-smokers,
      their families, the surrounding community and society at large. We find a lack of
      published evidence evaluating the effectiveness and consequences of these
      policies. By developing a model of policy effects, we outline possible unintended
      consequences. With such large gaps in the evidence base and the potential for
      deleterious consequences, we argue for increased discussion about the use of
      smoker-free employment policies as a public health intervention and for increased
      engagement of employers by the public health community in worksite health
      promotion.

PMID- 19168492
TI  - New Zealand: new graphic warnings encourage registrations with the quitline.

PMID- 19168493
TI  - Does inflammation influence atrial fibrillation recurrence following catheter
      ablation?

PMID- 19168494
TI  - Chagas cardiomyopathy and implantable cardioverter defibrillator implantation:
      similarities and differences with dilated cardiomyopathy.

PMID- 19168495
TI  - Different electrocardiographic manifestations of the cardioinhibitory vasovagal
      reflex.

PMID- 19168496
TI  - Improved cardiac performance through pacing-induced diaphragmatic stimulation: a
      novel electrophysiological approach in heart failure management?
AB  - AIMS: Pharmacological conditioning of the phrenic nerve can positively influence
      systolic performance, and diaphragm activation improves ventilatory function.
      Here we investigate whether pacing-induced diaphragmatic stimulation (PIDS) may
      improve left ventricular (LV) systolic function. METHODS AND RESULTS: We studied
      a total of 35 patients (4 females, mean age 67 +/- 9 years, ejection fraction 61
      +/- 14%) within 7 days following open heart surgery. The haemodynamic impact of
      different PIDS and ventricular pacing configurations and coupling intervals was
      tested in 132 episodes. Success of PIDS was assessed using fluoroscopy and
      palpation. Left ventricular systolic performance was recorded using the
      electromechanical activation time (EMAT) obtained through acoustic cardiography.
      Eighteen subjects were tested in the catheter laboratory and 17 in the intensive
      care unit. For both groups, EMAT significantly improved when the diaphragm was
      stimulated 20 ms after the onset of ventricular pacing. In all instances, PIDS
      could be induced with or without causing patient symptoms, and LV systolic
      performance improvement was comparable in symptomatic and asymptomatic modes. No
      desensitization of the diaphragm was observed following PIDS delivery 4-6 and 24
      h following open heart surgery. CONCLUSION: Pacing-induced diaphragmatic
      stimulation, if synchronized to the onset of ventricular contraction with a
      fixed, non-zero coupling delay, can improve LV systolic function reproducibly for
      at least 1 h without causing patient symptoms. The absence of diaphragm
      desensitization further underscores the potential of PIDS as a practical
      therapeutic approach in device-based heart failure management.

PMID- 19168497
TI  - Extraction of chronic pacemaker and defibrillator leads from the coronary sinus:
      laser infrequently used but required.
AB  - AIMS: Cardiac resynchronization therapy is an accepted treatment for heart
      failure but it may be necessary to explant these systems along with their leads.
      The evidence base for coronary sinus (CS) lead extractions is limited. We aimed
      to evaluate the percutaneous removal of these leads and the utility of laser
      extraction when necessary. METHODS AND RESULTS: Of 265 patients referred for lead
      extraction between January 2004 and June 2008, 32 (12.1%) involved CS leads (30
      males, mean age 67 years). Mean implantation time was 26.5 +/- 28.7 months (range
      1-116 months). Indications for extraction were pocket infection (34.4%), lead
      malfunction (43.8%), skin erosion (15.6%), and endocarditis (6.2%). Twenty-eight
      (87.5%) CS leads were removed with manual traction, with laser utilized in four
      cases (12.5%). No major complications of CS laceration, pericardial effusion,
      emergency surgery, or death occurred. CONCLUSION: Our experience supports the
      percutaneous extraction of CS leads as a safe and effective procedure including
      the utility of laser when necessary.

PMID- 19168498
TI  - Modified alternating current defibrillation: a new defibrillation technique.
AB  - AIMS: Defibrillation is the only clinically effective treatment for ventricular
      fibrillation (VF). Early defibrillation improves the outcome and increases the
      chance of survival with full recovery. Immediate availability of a home-based
      defibrillator using mains-derived alternating current (AC) current will
      drastically improve the outcome. The aim was to develop a defibrillator based on
      the modulated AC, resembling biphasic configuration, and compare its efficacy, in
      a pig model, with a standard direct current (DC) defibrillator. METHODS AND
      RESULTS: A computer controlled, modulated AC defibrillation system was developed
      using a high-voltage switch and a high-voltage transformer. The efficacy and
      safety was evaluated in five pigs (30-40 kg), under general anaesthesia with
      ketamine and isoflouran. A single quadripolar-pacing catheter was inserted
      percutaneously. Ventricular fibrillation was induced with rapid ventricular burst
      pacing, and stable VF was defibrillated after 15 s. Defibrillation threshold
      (DFT) was determined in each animal with AC and standard DC shock using the step
      down protocol. A biphasic-like shock was used with a short isoelectric stage
      between the phases. The DFT with AC was 70.83 +/- 24.81 J and with DC was 65.83
      +/- 12.41 J (P = 0.49). No macroscopic damage was observed after AC or DC
      defibrillation. CONCLUSION: Modulated AC defibrillation is safe and effective as
      the commercially available DC defibrillation. The defibrillator is built from an
      inexpensive high-voltage transformer, without the need for capacitor, batteries,
      or routine maintenance, delivers repeated shock without any delay, and provides
      pacing as well. It may be an ideal platform for automatic home defibrillator.

PMID- 19168499
TI  - Ventricular electrophysiology in congestive heart failure and its correlation
      with heart rate variability and baroreflex sensitivity: a canine model study.
AB  - AIMS: This study investigated ventricular electrophysiological characteristics
      and the correlation between these parameters and heart rate variability (HRV) and
      baroreflex sensitivity (BRS) in a canine congestive heart failure (CHF) model.
      METHODS AND RESULTS: Haemodynamics, HRV, BRS, and ventricular
      electrophysiological variables were measured 4-5 weeks after sham operation
      (control dogs) and pacemaker implantation, and rapid right ventricular pacing at
      240 bpm (CHF group). In the CHF group, significant differences from the control
      group in ventricular effective refractory period (VERP), monophasic action
      potential (MAP) duration (MAPD(90)), ventricular late repolarization duration
      (VLRD), the ratio of VERP to MAPD(90), dispersion of ventricular recovery time
      (VRT-D), and ventricular fibrillation threshold (VFT) were noted. Both BRS and
      the time and power domain parameters of HRV were significantly decreased in the
      CHF group compared with the control group, and a significant, positive
      correlation between HRV and BRS was identified in the CHF group. Heart rate
      variability and BRS were negatively and significantly correlated with VLRD and
      VRT-D, and were positively correlated with VERP/MAPD(90) and VFT in the CHF
      group. CONCLUSION: These results suggest that ventricular electrophysiological
      characteristics correlated with abnormal autonomic nerve function may have
      important effects on sudden cardiac death. Further research is warranted.

PMID- 19168500
TI  - Perforation of right ventricular free wall by pacemaker lead detected by
      multidetector computed tomography.
AB  - Pacemaker lead perforation is a recognized complication of lead implantation,
      particularly with active fixation leads. Multidetector computed tomography (MDCT)
      is emerging as the imaging modality of choice in diagnosing lead perforation,
      identifying associated sequelae such as pericardial effusion and planning
      extraction. We present a case illustrating the use of MDCT in a case of right
      ventricular (RV) lead perforation manifesting 5 days after cardiac
      resynchronization therapy pacing.

PMID- 19168501
TI  - Late perforation of a defibrillator lead managed by percutaneous, intravenous
      extraction.
AB  - We report the case of a patient with ischaemic cardiomyopathy who underwent
      cardiac resynchronization therapy with defibrillator back-up. He re-presented 3
      weeks later with chest pain, having received two shocks. We describe a case of
      late perforation with the Riata lead causing inappropriate shocks.

PMID- 19168502
TI  - Development and initial validation of a pictorial quality of life measure for
      young children with asthma.
AB  - OBJECTIVE: To develop and assess the psychometric properties of a pictorial
      version of the Pediatric Asthma Quality of Life Questionnaire (PAQLQ). METHODS: A
      pictorial PAQLQ was administered to 101 children with mild to severe asthma
      between 5 and 7 years of age. A subgroup of 48 children followed longitudinally
      completed the established version of the PAQLQ. RESULTS: A confirmatory factor
      analysis with modifications supported the factor structure of the established
      PAQLQ. The pictorial measure exhibited internal consistency reliability and
      convergent, discriminant, and predictive validity. CONCLUSIONS: Results suggest
      that the pictorial version of the PAQLQ has an underlying factor structure that
      is similar to that of the established PAQLQ. Future research with larger and
      diverse samples is needed to confirm the factor structure of the pictorial PAQLQ.

PMID- 19168503
TI  - Brief report: Hope, perceived maternal empathy, medical regimen adherence, and
      glycemic control in adolescents with type 1 diabetes.
AB  - OBJECTIVE: The relationships among hope, perceived maternal empathy, medical
      regimen adherence, and glycemic control in adolescents with type 1 diabetes were
      examined. METHOD: Twenty-nine girls and 21 boys with type 1 diabetes completed
      measures of hope, perceived maternal empathy, and medical regimen adherence. Each
      participant's most recent hemoglobin A1c, a measure of glycemic control, was
      obtained from the diabetes clinic database. RESULTS: Significant correlations
      were found among hope, perceived maternal empathy, and medical regimen adherence.
      Significant correlations were also found among hope, perceived maternal empathy,
      and glycemic control. Adolescents' perceptions of maternal empathy were
      positively correlated with level of hope. Hope appeared to mediate the
      relationship between perceived maternal empathy and adherence, as well as between
      perceived maternal empathy and glycemic control. CONCLUSIONS: The results of this
      study affirm the need for longitudinal research that examines the associations
      among hope, perceived maternal empathy, medical regimen adherence, and glycemic
      control.

PMID- 19168504
TI  - Health-related hindrance of personal goal pursuit and well-being of young adults
      with cystic fibrosis, pediatric cancer survivors, and peers without a history of
      chronic illness.
AB  - OBJECTIVE: Study examined content of personal goals, health-related hindrance
      (HRH; i.e., impact of health on goals), and relationship of HRH to health status
      and psychological well-being in young adults with cystic fibrosis (CF; n = 48),
      who survived childhood cancer (n = 57), and without history of chronic illness (n
      = 105). METHODS: Participants completed measures of life events, quality of life,
      psychological well-being, and goals. RESULTS: No group differences were found on
      goal content. HRH significantly related to subjective well-being and distress
      after controlling for demographics, negative life events, physical health-related
      quality of life, disease status, and self-efficacy. HRH related to health status
      variables. Cancer survivors without cancer late effects had significantly less
      HRH than the other groups. CONCLUSIONS: Health status may affect pursuit of
      personal goals and relate to well-being of young adults. The assessment of HRH
      has potential clinical utility for targeting interventions and warrants further
      research.

PMID- 19168505
TI  - Adult mouse intrahepatic biliary epithelial cells induced in vitro to become
      insulin-producing cells.
AB  - Transdifferentiation of cells from a patient's own liver into pancreatic beta
      cells could be useful for beta-cell replacement. We hypothesized that
      intrahepatic biliary epithelial cells (IHBECs) could become a new source of
      insulin-producing cells. IHBECs isolated from adult mice were expanded using our
      novel culture method termed, collagen-embedded floating culture method (CEFCM).
      With CEFCM, IHBECs formed three-dimensional ductal cysts and rapidly expanded
      their number by about 15-fold within 2 weeks. Over 90% of cells were positive for
      cytokeratin 7 and 19. At day 14, IHBECs were transfected with adenoviral (Ad)-
      pancreas duodenum homeobox 1 (Pdx-1), NeuroD or Pdx-1/VP16. After 7 additional
      days in serum- and insulin-free differentiation medium (DM), cell phenotypes were
      determined by RT-PCR, immunostaining and ELISA for insulin. In DM control IHBECs
      started to express some endocrine progenitor genes (Neurog3, NeuroD, Nkx6.1, and
      Pdx-1) but lacked insulin gene (Ins) mRNA. Transduced expression of PDX-1, NEUROD
      or PDX-1/VP16 led to expression of not only INS but also GLUT2 and prohormone
      convertase 1 and 2. About 3% of 4000 cells counted in PDX-1/VP16 transduced
      cultures stained strongly for C-peptide suggesting that a subpopulation may have
      the capacity for differentiation. Transduced cells released insulin (Ad-PDX-1
      0.08+/-0.05, Ad-NEUROD 0.33+/-0.09, Ad-PDX-1/VP16 0.37+/-0.14 ng/1x10(5) cells
      after 48 h in culture). IHBECs can be markedly expanded, and then with molecular
      manipulation a subpopulation of these cells can differentiate towards a beta-cell
      phenotype. This approach may lead to a new source of beta-cells that can be used
      for transplantation in diabetes.

PMID- 19168506
TI  - Minimal oxidative load: a prerequisite for thyroid cell function.
AB  - In addition to reactive oxygen species (ROS) produced by mitochondria during
      aerobic respiration, thyrocytes are continuously producing H(2)O(2), a key
      element for hormonogenesis. Because nothing is known about ROS implication in
      normal non-stimulated cells, we studied their possible involvement in thyrocytes
      incubated with a potent antioxidant, N-acetylcysteine (NAC). NAC, which blocked
      the production of intracellular ROS, also decreased dual oxidases,
      thyroperoxidase, pendrin, and thyroglobulin protein and/or gene expression. By
      contrast, Na(+)/I(-) symporter mRNA expression was unaffected. Among antioxidant
      systems, peroxiredoxin (PRDX) five expression was reduced by NAC, whereas
      peroxiredoxin three increased and catalase remained unchanged. In vivo, the
      expression of both dual oxidases and peroxiredoxin five proteins was also
      decreased by NAC. In conclusion, when intracellular ROS levels drop below a basal
      threshold, the expression of proteins involved in thyroid cell function is
      hampered. This suggests that keeping ROS at a minimal level is required for
      safeguarding thyrocyte function.

PMID- 19168507
TI  - Inflammation in chronic heart failure: what is familiar, what is unfamiliar?

PMID- 19168508
TI  - Immunological mechanisms of pentoxifylline in chronic heart failure.
AB  - The progressive syndrome of chronic heart failure (CHF) represents a common
      disease pathway that may be derived from a host of varying insults (including
      myocardial ischaemia and infarction, hypertension, viral infection, pregnancy,
      etc). Despite this multifarious aetiology, a common phenomena observed in CHF
      patients is elevated levels of tumour necrosis factor (TNF)-alpha. This has led
      to the widespread concept that TNF-alpha is directly involved in the
      pathophysiology of CHF and as such, attempts have been made to inhibit TNF-alpha
      production in this cohort. However, to date, there have been no clear beneficial
      effects from TNF-alpha inhibition and indeed trials of direct anti-TNF therapy
      have provoked worsening of clinical outcomes. Conversely, a possible exception is
      pentoxifylline (PTX), a putative TNF-alpha inhibitor with possible (but ill
      defined) vasodilatory properties. Several small clinical trials assessing the use
      of PTX in CHF have suggested beneficial effects on multiple surrogate clinical
      markers. Interestingly, these trials failed to show a concordant effect on
      circulating TNF despite the clinical improvement, suggesting other key beneficial
      properties of this novel agent. This review article provides an insight into the
      potential beneficial mode of the action of PTX in CHF and calls for more
      investigation of this interesting agent.

PMID- 19168511
TI  - Isoproterenol-induced heart failure in the rat is associated with nitric oxide
      dependent functional alterations of cardiac function.
AB  - AIMS: The role of nitric oxide (NO) in heart failure (HF) is complex and remains
      controversial. We tested the hypothesis that the role of NO in isolated atria and
      cardiomyocytes is altered in isoproterenol-induced HF. METHODS AND RESULTS: Rats
      received isoproterenol (ISO, 5 mg/kg/day, intraperitoneally) or vehicle for 1
      week. Haemodynamic parameters were obtained by left ventricular catheterization.
      Effects of NOS inhibition on isolated atria and on electrically paced left
      ventricular myocytes were determined. Additionally, expressions of nitric oxide
      synthases and their allosteric modulators hsp90, caveolin-1, and caveolin-3
      proteins in the left ventricles were measured. ISO increased left ventricular
      mass by 33% and decreased indices of left ventricular systolic and diastolic
      function dp/dtmin and dp/dtmax (both P<0.05). Isolated atria from HF rats had a
      lower spontaneous beating rate (P<0.05). NOS inhibition by L-NAME increased basal
      frequency and attenuated the positive chronotropic effect of beta-adrenergic
      stimulation in the HF group (P<0.05). Ventricular myocytes from failing hearts
      had impaired cell shortening. L-NAME decreased contractility of control, but not
      failing myocytes. Left ventricular expressions of eNOS, hsp90, iNOS, but not nNOS
      or caveolins, were increased. CONCLUSION: Despite the increased capacity for NO
      synthesis in isoproterenol-induced HF, NO does not sustain contractility of
      failing myocytes. NO may contribute to the decreased basal heart rate and it may
      accelerate beta-adrenergic stimulation of chronotropy.

PMID- 19168509
TI  - Inflammation as a therapeutic target in heart failure? A scientific statement
      from the Translational Research Committee of the Heart Failure Association of the
      European Society of Cardiology.
AB  - The increasing prevalence of heart failure poses enormous challenges for health
      care systems worldwide. Despite effective medical interventions that target
      neurohumoral activation, mortality and morbidity remain substantial. Evidence for
      inflammatory activation as an important pathway in disease progression in chronic
      heart failure has emerged in the last two decades. However, clinical trials of
      'anti-inflammatory' therapies (such as anti-tumor necrosis factor-alpha
      approaches) have to date failed to show benefit in heart failure patients. The
      Heart Failure Association of the European Society of Cardiology recently
      organized an expert workshop to address the issue of inflammation in heart
      failure from a basic science, translational and clinical perspective, and to
      assess whether specific inflammatory pathways may yet serve as novel therapeutic
      targets for this condition. This consensus document represents the outcome of the
      workshop and defines key research questions that still need to be addressed as
      well as considering the requirements for future clinical trials in this area.

PMID- 19168510
TI  - Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and
      epidemiology.
AB  - Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are global
      epidemics incurring significant morbidity and mortality. The combination presents
      many diagnostic challenges. Clinical symptoms and signs frequently overlap.
      Evaluation of cardiac and pulmonary function is often problematic and
      occasionally misleading. Echocardiography and pulmonary function tests should be
      performed in every patient. Careful interpretation is required to avoid
      misdiagnosis and inappropriate treatment. Airflow obstruction, in particular,
      must be demonstrated when clinically euvolaemic. Very high and very low
      concentrations of natriuretic peptides have high positive and negative predictive
      values for diagnosing HF in those with both conditions. Intermediate values are
      less informative. Both conditions are systemic disorders with overlapping
      pathophysiological processes. In patients with HF, COPD is consistently an
      independent predictor of death and hospitalization. However, the impact on
      ischaemic and arrhythmic events is unknown. Greater collaboration is required
      between cardiologists and pulmonologists to better identify and manage concurrent
      HF and COPD. The resulting symptomatic and prognostic benefits outweigh those
      attainable by treating either condition alone.

PMID- 19168512
TI  - Transplantation of mesenchymal stem cells within a poly(lactide-co-epsilon
      caprolactone) scaffold improves cardiac function in a rat myocardial infarction
      model.
AB  - AIMS: Cardiac tissue engineering has been proposed as an appropriate method to
      repair myocardial infarction (MI). Evidence suggests that a cell with scaffold
      combination was more effective than a cell-only implant. Nevertheless, to date,
      there has been no research into elastic biodegradable poly(lactide-co-epsilon
      caprolactone) (PLCL) scaffolds. The aim of this study was to investigate the
      effect of mesenchymal stem cells (MSCs) with elastic biodegradable PLCL scaffold
      transplants in a rat MI model. METHODS AND RESULTS: Ten days after inducing MI
      through the cryoinjury method, a saline control, MSC, PLCL scaffold, or MSC
      seeded PLCL scaffold was transplanted onto the hearts. Four weeks after
      transplantation, cardiac function and histology were evaluated. Transplanted MSCs
      survived and differentiated into cardiomyocytes in the injured region. Left
      ventricular ejection fraction in the MSC+PLCL group increased by 23% compared
      with that in the saline group; it was also higher in the MSC group. The infarct
      area in the MSC+PLCL group was decreased by 29% compared with that in the saline
      group; it was also reduced in the MSC group. CONCLUSION: Mesenchymal stem cells
      plus PLCL should be an excellent combination for cardiac tissue engineering.

PMID- 19168513
TI  - Cyclophosphamide-evoked heart failure involves pronounced co-suppression of
      cytoplasmic thioredoxin reductase activity and non-protein free thiol level.
AB  - AIMS: Heart failure is a life-threatening complication of high-dose
      cyclophosphamide (CTX) chemotherapy, and the present study aimed at identifying
      the mechanism involved in mice. METHODS AND RESULTS: CTX at 800 mg/kg resulted in
      heart failure, in which cytoplasmic thioredoxin reductase (TrxR1) activity and
      non-protein free thiol (NPFT) level were suppressed by 90 and 62%, respectively.
      The combination of 350 mg/kg CTX and the glutathione synthesis inhibitor
      buthionine sulfoximine (BSO) also evoked heart failure, in which TrxR1 activity
      and NPFT level were suppressed by 66 and 62%, respectively. NPFT depletion alone
      by BSO did not cause cardiac toxicity. CTX at 350 mg/kg alone also did not cause
      cardiac toxicity, even though it suppressed TrxR1 activity by 68%. Previous
      studies have shown that half inactivation of TrxR1 in tumour, bladder, and
      kidneys was associated with toxicological consequences. Cardiac TrxR1 is
      dispensable, but cardiac cytoplasmic thioredoxin (Trx1) is essential. The
      potential uncoupling between TrxR1 and Trx1 may explain why there is no cardiac
      toxicity following TrxR1 inhibition. However, TrxR1 inactivation may still play a
      role in CTX-evoked heart failure because inactivated TrxR1 gains cytotoxic
      function, which may engender noticeable toxicity when massive NPFT is deleted.
      CONCLUSION: CTX-evoked heart failure involves pronounced co-suppression of TrxR1
      activity and NPFT level.

PMID- 19168514
TI  - Self-assessment of health status is associated with inflammatory activation and
      predicts long-term outcomes in chronic heart failure.
AB  - AIMS: Clinicians lack a generally accepted means for health status assessment in
      chronic heart failure (CHF). We investigated the correlation between health
      status and inflammation burden as well as its long-term prognostic value in CHF
      outpatients. METHODS AND RESULTS: Kansas City Cardiomyopathy Questionnaires
      (KCCQ) were completed by 137 CHF outpatients (aged 64+/-12 years, mean ejection
      fraction 27+/-7%). Inflammatory markers [interleukin (IL)-6, IL-10, TNF-alpha,
      soluble Fas, Fas ligand, ICAM-1, VCAM-1], plasma B-type natriuretic peptide
      (BNP), 6 min walk test (6MWT), Zung self-rating depression scale, and Beck
      Depression Inventory were also assessed. Patients were followed for major
      cardiovascular events (death or hospitalization for disease progression) for up
      to 250 days. Patients with worse KCCQ-summary (KCCQ-s<50) score had lower 6MWT
      (P<0.05), and higher BNP (P<0.05) and pro-inflammatory markers (P<0.05) than
      those with KCCQ-s>or=50. Worse health status was also associated with shorter
      event-free survival (115+/-12 days for KCCQ-s<50 vs. 214+/-15 days for KCCQ
      s>or=50, P=0.0179). Separating patients according KCCQ-functional score (KCCQ-f,
      cut-off 50) showed similar results. In multivariate Cox regression analysis, only
      LVEF (HR=0.637, 95% CI 0.450-0.900, P=0.011) and KCCQ-f (HR=0.035, 95% CI 0.002
      0.824, P=0.037) were independent predictors of event-free survival at 250 days.
      CONCLUSION: KCCQ-s reflects neurohormonal and inflammatory burden in CHF. Among
      studied questionnaires, only KCCQ-f is an independent predictor of long-term
      event-free survival in CHF.

PMID- 19168515
TI  - Liver function abnormalities and outcome in patients with chronic heart failure:
      data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality
      and Morbidity (CHARM) program.
AB  - AIMS: The prevalence and importance of liver function test (LFT) abnormalities in
      a large contemporary cohort of heart failure patients have not been
      systematically evaluated. METHODS AND RESULTS: We characterized the LFTs of 2679
      patients with symptomatic chronic heart failure from the Candesartan in Heart
      failure: Assessment of Reduction in Mortality and morbidity program (CHARM). We
      used multivariable modelling to assess the relationships between baseline LFT
      values and long-term outcomes. Liver function test abnormalities were common in
      patients with chronic heart failure, ranging from alanine aminotransferase
      elevation in 3.1% of patients to low albumin in 18.3% of patients; total
      bilirubin was elevated in 13.0% of patients. In multivariable analysis, elevated
      total bilirubin was the strongest LFT predictor of adverse outcome for both the
      composite outcome of cardiovascular death or heart failure hospitalization (HR
      1.21 per 1 SD increase, P<0.0001) and all-cause mortality (HR 1.19 per 1 SD
      increase, P<0.0001). Even after adjustment for other variables, elevated total
      bilirubin was one of the strongest independent predictors of poor prognosis (by
      global chi-square). CONCLUSION: Bilirubin is independently associated with
      morbidity and mortality. Changes in total bilirubin may offer insight into the
      underlying pathophysiology of chronic heart failure.

PMID- 19168516
TI  - Prevalence and prognostic significance of adrenergic escape during chronic beta
      blocker therapy in chronic heart failure.
AB  - AIMS: Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to beta
      blockers appears conceivable in chronic heart failure (CHF), as generalized
      systemic neurohumoral activation has been described as the pathophysiological
      basis of this syndrome. The aim of this study was to examine the prevalence and
      prognostic value of AE with respect to different beta-blocker agents and doses.
      METHODS AND RESULTS: This was a prospective, observational study of 415 patients
      with systolic CHF receiving chronic stable beta-blocker therapy. AE was defined
      by norepinephrine levels above the upper limit of normal. Irrespective of the
      individual beta-blocker agents used and the dose equivalent taken, the prevalence
      of AE was 31-39%. Norepinephrine levels neither correlated with heart rate
      (r=0.02; 95% CI: -0.08-0.11; P=0.74) nor were they related to underlying rhythm
      (P=0.09) or the individual beta-blocker agent used (P=0.87). The presence of AE
      was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI:
      1.387-2.645; chi2: 15.60). CONCLUSION: We verified the presence of AE in CHF
      patients on chronic stable beta-blocker therapy, irrespective of the individual
      beta-blocker agent and the dose equivalent. As AE might indicate therapeutic
      failure, the determination of AE could help to identify those patients with CHF
      that might benefit from more aggressive treatment modalities. Heart rate,
      however, is not a surrogate for adrenergic escape.

PMID- 19168517
TI  - The cyclic guanosine monophosphate/B-type natriuretic peptide ratio and mortality
      in advanced heart failure.
AB  - AIMS: Attenuation of the effects of natriuretic peptides has been demonstrated in
      animal models but studies in humans are scarce, particularly concerning renal
      attenuation. We investigated the attenuation of B-type natriuretic peptide (BNP)
      in chronic advanced heart failure (HF). METHODS AND RESULTS: We included 62
      outpatients with HF and severe left ventricular systolic dysfunction. Cases had
      at least one hospital admission or emergency department visit for acute HF in the
      previous year and were in NYHA class III/IV despite optimized therapy. The
      individual age- and sex-matched controls were symptomatically controlled (NYHA I
      and II). We collected 24 h urine and a blood sample from all patients. Plasma BNP
      and plasma (pcGMP) and urine cyclic guanosine monophosphate (ucGMP) were
      measured. Patients were followed for 3 months for hospital admission or all-cause
      death. ucGMP to plasma BNP (ucGMP/BNP) ratio was attenuated in cases vs. controls
      [median (IQR): 8354 (4293-16,456) vs. 12,693 (6896-22,851)]. There were no
      differences in pcGMP to BNP (pcGMP/BNP) ratio or urine cGMP excretion. Patients
      with worse outcome had lower pcGMP/BNP [260 (86-344) vs. 381 (244-728) in
      patients without adverse outcome events] and lower ucGMP/BNP [4146 (2207-9363)
      vs. 10,922 (7495-19,971)]. CONCLUSION: Renal NP's second messenger production is
      attenuated in advanced HF. Patients with worse outcome have lower ucGMP/BNP and
      pcGMP/BNP ratios.

PMID- 19168518
TI  - Diagnosis of heart failure with preserved ejection fraction: improved accuracy
      with the use of markers of collagen turnover.
AB  - AIMS: Heart failure with preserved ejection fraction (HF-PEF) can be difficult to
      diagnose in clinical practice. Myocardial fibrosis is a major determinant of
      diastolic dysfunction (DD), potentially contributing to the progression of HF
      PEF. The aim of this study was to analyse whether serological markers of collagen
      turnover may predict HF-PEF and DD. METHODS AND RESULTS: We included 85 Caucasian
      treated hypertensive patients (DD n=65; both DD and HF-PEF n=32). Serum carboxy
      (PICP), amino (PINP), and carboxytelo (CITP) peptides of procollagen type I,
      amino (PIIINP) peptide of procollagen type III, matrix metalloproteinases (MMP-1,
      MMP-2, and MMP-9), and tissue inhibitor of MMP levels were assayed. Using
      receiver operating characteristic curve analysis, MMP-2 (AUC=0.91; 95% CI: 0.84,
      0.98), CITP (0.83; 0.72, 0.92), PICP (0.82; 0.72, 0.92), B-type natriuretic
      peptide (BNP) (0.82; 0.73, 0.91), MMP-9 (0.79; 0.68, 0.89), and PIIINP (0.78;
      0.66, 0.89) levels were significant predictors of HF-PEF (P<0.01 for all).
      Carboxytelo peptides of procollagen type I (AUC=0.74; 95% CI: 0.62, 0.86), MMP-2
      (0.73; 0.62, 0.84), PIIINP (0.73; 0.60, 0.85), BNP (0.69; 0.55, 0.83) and PICP
      (0.66; 0.54, 0.78) levels were significant predictors of DD (P<0.05 for all). A
      cutoff of 1585 ng/mL for MMP-2 provided 91% sensitivity and 76% specificity for
      predicting HF-PEF and combinations of biomarkers could be used to adjust either
      sensitivity or specificity. CONCLUSION: Markers of collagen turnover identify
      patients with HF-PEF and DD. Matrix metalloproteinase 2 may be more useful than
      BNP in the identification of HF-PEF. This suggests that these new biochemical
      tools may assist in identifying patients with these diagnostically challenging
      conditions.

PMID- 19168519
TI  - Rationale and design of the Karolinska-Rennes (KaRen) prospective study of
      dyssynchrony in heart failure with preserved ejection fraction.
AB  - AIMS: Heart failure with preserved ejection fraction (HFPEF) is common but not
      well understood. Electrical dyssynchrony in systolic heart failure is harmful.
      Little is known about the prevalence and the prognostic impact of dyssynchrony in
      HFPEF. METHODS AND RESULTS: We have designed a prospective, multicenter,
      international, observational study to characterize HFPEF and to determine whether
      electrical or mechanical dyssynchrony affects prognosis. Patients presenting with
      acute heart failure (HF) will be screened so as to identify 400 patients with
      HFPEF. Inclusion criteria will be: acute presentation with Framingham criteria
      for HF, left ventricular ejection fraction>or=45%, brain natriuretic peptide
      (BNP)>100 pg/mL or NT-proBNP>300 pg/mL. Once stabilized, 4-8 weeks after the
      index presentation, patients will return and undergo questionnaires, serology,
      ECG, and Doppler echocardiography. Thereafter, patients will be followed for
      mortality and HF hospitalization every 6 months for at least 18 months. Sub
      studies will focus on echocardiographic changes from the acute presentation to
      the stable condition and on exercise echocardiography, cardiopulmonary exercise
      testing, and serological markers. CONCLUSION: KaRen aims to characterize
      electrical and mechanical dyssynchrony and to assess its prognostic impact in
      HFPEF. The results might improve our understanding of HFPEF and generate answers
      to the question whether dyssynchrony could be a target for therapy in HFPEF.

PMID- 19168520
TI  - A randomized trial of the addition of home-based exercise to specialist heart
      failure nurse care: the Birmingham Rehabilitation Uptake Maximisation study for
      patients with Congestive Heart Failure (BRUM-CHF) study.
AB  - AIMS: Supervised exercise can benefit selected patients with heart failure,
      however the effectiveness of home-based exercise remains uncertain. We aimed to
      assess the effectiveness of a home-based exercise programme in addition to
      specialist heart failure nurse care. METHODS AND RESULTS: This was a randomized
      controlled trial of a home-based walking and resistance exercise programme plus
      specialist nurse care (n=84) compared with specialist nurse care alone (n=85) in
      a heart failure population in the West Midlands, UK. PRIMARY OUTCOME: Minnesota
      Living with Heart Failure Questionnaire (MLwHFQ) at 6 and 12 months. SECONDARY
      OUTCOMES: composite of death, hospital admission with heart failure or myocardial
      infarction; psychological well-being; generic quality of life (EQ-5D); exercise
      capacity. There was no statistically significant difference between groups in the
      MLwHFQ at 6 month (mean, 95% CI) (-2.53, -7.87 to 2.80) and 12 month (-0.55, 
      5.87 to 4.76) follow-up or secondary outcomes with the exception of a higher EQ
      5D score (0.11, 0.04 to 0.18) at 6 months and lower Hospital Anxiety and
      Depression Scale score (-1.07, -2.00 to -0.14) at 12 months, in favour of the
      exercise group. At 6 months, the control group showed deterioration in physical
      activity, exercise capacity, and generic quality of life. CONCLUSION: Home-based
      exercise training programmes may not be appropriate for community-based heart
      failure patients.

PMID- 19168521
TI  - Clinical trials update from the Heart Failure Society of America and the American
      Heart Association meetings in 2008: SADHART-CHF, COMPARE, MOMENTUM, thyroid
      hormone analogue study, HF-ACTION, I-PRESERVE, beta-interferon study, BACH, and
      ATHENA.
AB  - This article provides information and a commentary on trials relevant to the
      pathophysiology, prevention, and treatment of heart failure presented at the
      Heart Failure Society of America and the American Heart Association meetings in
      2008. Unpublished reports should be considered as preliminary, as analyses may
      change in the final publication. (i) SADHART-CHF showed no difference in outcome
      for heart failure patients with depression treated with sertraline compared with
      placebo. (ii) A controlled release carvedilol formulation showed similar LV
      haemodynamic effects to the standard carvedilol formulation in the COMPARE study.
      (iii) A post hoc analysis of the MOMENTUM study suggested that patients with less
      severe heart failure may be more likely to benefit from a continuous aortic flow
      augmentation device. (iv) A thyroid hormone analogue was poorly tolerated in
      patients with heart failure. (v) HF-ACTION showed that exercise training is safe
      and offers modest clinical benefits in patients with heart failure. (vi)
      Irbesartan failed to improve outcomes in patients with preserved ejection
      fraction in the I-PRESERVE study. (vii) A phase II study of beta-interferon
      administration in patients with dilated cardiomyopathy showed encouraging
      results. (viii) The BACH study showed that mid-regional pro-adrenomedullin was
      more accurate than BNP or NT-proBNP at predicting outcome at 90 days in patients
      with acute heart failure. (ix) A secondary analysis from ATHENA showed a
      reduction in cardiovascular hospitalizations and strokes for patients with atrial
      fibrillation receiving dronedarone compared with placebo.

PMID- 19168522
TI  - Rapid left ventricular recovery after cabergoline treatment in a patient with
      peripartum cardiomyopathy.
AB  - The aetiology of peripartum cardiomyopathy (PPCM) is still largely unknown.
      Recent evidence suggests that the breakdown products from prolactin can induce
      cardiomyopathy. Prolactin secretion can be reduced with bromocriptine which had
      beneficial effects in a small study. We present a case of a patient with PPCM who
      received cabergoline, a strong and long lasting antagonist of prolactin
      secretion. Following treatment, her prolactin levels dropped swiftly. N-terminal
      pro-BNP levels, which had remained high up to that point, dropped within 1 day
      (7006 to 4408 pg/mL). Echocardiographic left ventricular ejection fraction
      recovered from 26% on day 4 postpartum to 32% and later 47% on days 2 and 5 after
      cabergoline treatment. To our knowledge, this is the first description of a case
      of PPCM in which cabergoline was administered.

PMID- 19168524
TI  - Indication for bromocriptine in peripartum cardiomyopathy.

PMID- 19168525
TI  - Survival benefit after percutaneous treatment of chronic total coronary
      occlusions.

PMID- 19168526
TI  - Growth differentiation factor-15 as a prognostic marker in patients with acute
      myocardial infarction.
AB  - AIMS: Our aim was to assess the long-term prognostic value of growth
      differentiation factor-15 (GDF-15) in patients post-acute myocardial infarction
      (AMI). Growth differentiation factor-15 is a member of the transforming growth
      factor beta family. Growth differentiation factor-15 is expressed in the
      myocardium and upregulated due to 'stress' and has been shown to have
      antiapoptotic actions. Its role in the cardiovascular system however is not well
      defined. We were interested to see if GDF-15 could provide long-term prognostic
      value in post-AMI patients. We compared GDF-15 with N-terminal pro-B-type
      natriuretic peptide (NT-proBNP). METHODS AND RESULTS: We recruited 1142
      consecutive post-AMI patients [820 men, median (range) age 67 (24-97) years] in a
      prospective study with a follow-up period of 505 (range 1-2837) days. Growth
      differentiation factor-15 levels increased with increasing Killip class (P <
      0.001) and were correlated with NT-proBNP (r = 0.47, P < 0.001). Using a
      multivariable Cox proportional hazards model, log GDF-15 (HR 1.77), log NT-proBNP
      (HR 2.06), age (HR 1.03) Killip class above 1, (HR 1.62), use of beta-blockers
      (HR 0.54) and past history of MI (HR 1.44) were significant independent
      predictors of death or heart failure (HF). Predictors of death were log NT
      proBNP, log GDF-15, age, eGFR, past history of MI, use of beta-blockers, and use
      of ACE inhibitors or angiotensin receptor blockers. The C-statistic for GDF-15
      for predicting death or HF at 1 year was 0.73 (95% CI: 0.70-0.76, P < 0.001) and
      was 0.76 (95% CI: 0.70-0.80, P < 0.001) for NT-proBNP. Combining these markers
      yielded an AUC of 0.81 (95% CI: 0.77-0.85), which exceeded that of GDF-15 (P <
      0.001) and NT-proBNP (P = 0.004) alone. The Kaplan-Meier analysis revealed that
      those patients with above median GDF-15 and NT-proBNP had the highest event rate
      for death and HF (log rank 50.22, P < 0.001). CONCLUSION: Growth differentiation
      factor-15 is a new marker for predicting death and HF in post-AMI patients. GDF
      15 provides prognostic information over and above clinical factors and the
      established biomarker NT-proBNP. Combined levels of GDF-15 with NT-proBNP can
      identify a high-risk group of patients.

PMID- 19168527
TI  - Coronary artery fistula documented by invasive and non-invasive image techniques.

PMID- 19168528
TI  - Three-dimensional echocardiography for optimization of cardiac resynchronization
      therapy.

PMID- 19168529
TI  - A systematic review and meta-analysis of intra-aortic balloon pump therapy in ST
      elevation myocardial infarction: should we change the guidelines?
AB  - Aims Intra-aortic balloon counterpulsation (IABP) in ST-segment elevation
      myocardial infarction (STEMI) with cardiogenic shock is strongly recommended
      (class IB) in the current guidelines. We performed meta-analyses to evaluate the
      evidence for IABP in STEMI with and without cardiogenic shock. Methods and
      results Medical literature databases were scrutinized to identify randomized
      trials comparing IABP with no IABP in STEMI. In absence of randomized trials,
      cohort studies of IABP in STEMI with cardiogenic shock were identified. Two
      separate meta-analyses were performed respectively. The first meta-analysis
      included seven randomized trials (n = 1009) of STEMI. IABP showed neither a 30
      day survival benefit nor improved left ventricular ejection fraction, while being
      associated with significantly higher stroke and bleeding rates. The second meta
      analysis included nine cohorts of STEMI patients with cardiogenic shock (n =
      10529). In patients treated with thrombolysis, IABP was associated with an 18%
      [95% confidence interval (CI), 16-20%; P < 0.0001] decrease in 30 day mortality,
      albeit with significantly higher revascularization rates compared to patients
      without support. Contrariwise, in patients treated with primary percutaneous
      coronary intervention, IABP was associated with a 6% (95% CI, 3-10%; P < 0.0008)
      increase in 30 day mortality. Conclusion The pooled randomized data do not
      support IABP in patients with high-risk STEMI. The meta-analysis of cohort
      studies in the setting of STEMI complicated by cardiogenic shock supported IABP
      therapy adjunctive to thrombolysis. In contrast, the observational data did not
      support IABP therapy adjunctive to primary PCI. All available observational data
      concerning IABP therapy in the setting of cardiogenic shock is importantly
      hampered by bias and confounding. There is insufficient evidence endorsing the
      current guideline recommendation for the use of IABP therapy in the setting of
      STEMI complicated by cardiogenic shock. Our meta-analyses challenge the current
      guideline recommendations.

PMID- 19168530
TI  - Paracardiac mass with possible cardiac infiltration: the incremental clinical
      value of multimodality non-invasive imaging.

PMID- 19168531
TI  - Association between hormone replacement therapy and subsequent arterial and
      venous vascular events: a meta-analysis.

PMID- 19168532
TI  - Cardiovascular flashlight. Multi-vessel coronary artery spasm.

PMID- 19168534
TI  - Blood pressure reduction and renin-angiotensin system inhibition for prevention
      of congestive heart failure: a meta-analysis.
AB  - AIMS: It is unclear whether prevention of congestive heart failure (CHF) by drugs
      that inhibit the renin-angiotensin system (RAS) occurs over and beyond the
      reduction in blood pressure (BP) achieved by these drugs. METHODS AND RESULTS: We
      conducted a meta-analysis of trials comparing angiotensin-converting enzyme
      inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), or calcium-channel
      blockers (CCBs), with diuretics, beta-blockers, or placebo in hypertensive or
      high-risk subjects without CHF at entry. Both fixed- and random-effect models
      were used. In trials vs. placebo, the risk of CHF was reduced by 21% with ACEIs
      (P = 0.007), whereas the effect of ARBs and CCBs was not significant (random
      effect models). Thus, CCBs did not increase the risk of CHF. In trials vs.
      diuretics/beta-blockers, no differences were found between ACEIs and comparators
      [odds ratio (OR) 1.02; 95% confidence interval (CI) 0.84-1.24], whereas CCBs were
      associated with an 18% higher risk of CHF (OR 1.18; 95% CI 1.00-1.39; P = 0.048).
      Therefore, ACEIs were not superior to diuretics/beta-blockers for the prevention
      of CHF. Because heterogeneity between trials was significant, we investigated
      potential sources of heterogeneity by meta-regression. The risk of CHF decreased
      by 24% (P < 0.001) for each 5 mmHg reduction in systolic BP. The risk of CHF was
      19% less with ACEIs/ARBs than CCBs (P < 0.001) and 16% less in studies without
      multiple risk factors required for entry (P = 0.009). CONCLUSION: BP reduction is
      beneficial for the prevention of CHF. Over and beyond BP reduction, the
      protective effect of ACEIs and ARBs is greater than that of CCBs.

PMID- 19168535
TI  - NHS 10 years away from harnessing the benefits of genome medicine.

PMID- 19168533
TI  - Asymptomatic ST-segment depression during exercise testing and the risk of sudden
      cardiac death in middle-aged men: a population-based follow-up study.
AB  - AIMS: Silent electrocardiographic ST change predicts future coronary events in
      patients with coronary heart disease (CHD), but the prognostic significance of
      asymptomatic ST-segment depression with respect to sudden cardiac death in
      subjects without apparent CHD is not well known. METHODS AND RESULTS: We
      investigated the association between silent ST-segment depression during and
      after maximal symptom-limited exercise test and the risk of sudden cardiac death
      in a population-based sample of 1769 men without evident CHD. A total of 72
      sudden cardiac death occurred during the median follow-up of 18 years. The risk
      of sudden cardiac death was increased among men with asymptomatic ST-segment
      depression during exercise [hazard ratio (HR) 2.1, 95% confidence interval (CI)
      1.2-3.9] as well as among those with asymptomatic ST-segment depression during
      recovery period (HR 3.2, 95% CI 1.7-6.0). Asymptomatic ST-depression during
      exercise testing was a stronger predictor for the risk of sudden cardiac death
      especially among smokers as well as in hypercholesterolaemic and hypertensive men
      than in men without these risk factors. CONCLUSION: Asymptomatic ST-segment
      depression was a very strong predictor of sudden cardiac death in men with any
      conventional risk factor but no previously diagnosed CHD, emphasizing the value
      of exercise testing to identify asymptomatic high-risk men who could benefit from
      preventive measures.

PMID- 19168536
TI  - Corticosteroid injection for rotator cuff disease.

PMID- 19168538
TI  - Presumed consent to access medical records removed from NHS constitution after
      protests.

PMID- 19168537
TI  - Subacromial ultrasound guided or systemic steroid injection for rotator cuff
      disease: randomised double blind study.
AB  - OBJECTIVE: To compare the effectiveness of ultrasound guided corticosteroid
      injection in the subacromial bursa with systemic corticosteroid injection in
      patients with rotator cuff disease. DESIGN: Double blind randomised clinical
      trial. SETTING: Outpatient clinic of a physical medicine and rehabilitation
      department in Oslo, Norway. Patients 106 patients with rotator cuff disease
      lasting at least three months. INTERVENTIONS: Ultrasound guided corticosteroid
      and lidocaine injection in the subacromial bursa and lidocaine injection in the
      gluteal region (local group); corticosteroid and lidocaine injection in the
      gluteal region and ultrasound guided lidocaine injection in the subacromial bursa
      (systemic group). MAIN OUTCOME MEASURES: Difference in improvement in the overall
      shoulder pain and disability index score after six weeks. RESULTS: Six weeks
      after the intervention, the mean difference in improvement in overall shoulder
      pain and disability index score between the local group and the systemic group
      was -5.2 (95% confidence interval -13.9 to 3.5); it was -4.1 (-12.3 to 4.1,
      P=0.32) after adjustment for baseline score. A small but statistically
      significant difference in improvement between groups occurred in favour of the
      local group for two secondary outcome measures: the Western Ontario rotator cuff
      index (8.1, 0.7 to 15.6) and change in main complaint (2.0, 0 to 4). CONCLUSIONS:
      No important differences in short term outcomes were found between local
      ultrasound guided corticosteroid injection and systemic corticosteroid injection
      in rotator cuff disease. TRIAL REGISTRATION: Clinical trials NCT00640575.

PMID- 19168540
TI  - Dietary pectin up-regulates monocaboxylate transporter 1 in the rat
      gastrointestinal tract.
AB  - This work was undertaken to study the effect of pectin feeding on the expression
      level, cellular localization and functional activity of monocarboxylate
      transporter 1 (MCT1) in the gastrointestinal tract of rats. The results indicated
      that MCT1 protein level was significantly increased along the entire length of
      the gastrointestinal tract of pectin-fed rats in comparison with control animals.
      Immunohistochemical analysis revealed an increase in MCT1 in the stratified
      squamous epithelia of the forestomach as well as in the basolateral membranes of
      the cells lining the gastric pit of the glandular stomach of pectin-fed rats when
      compared with control animals. The parietal cells, which showed barely any or no
      detectable MCT1 in the control group, exhibited a strong intensity of MCT1 on the
      basolateral membranes in pectin-fed rats. In the small intestine of pectin-fed
      rats, strong immunopositivity for MCT1 was detected in the brush border and
      basolateral membranes of the absorptive enterocytes lining the entire villi,
      while in control rats, weak reactivity was detected on the brush border membrane
      in a few absorptive enterocytes in the villus tip. In the large intestine of
      control animals, MCT1 was detected on the basolateral membranes of the epithelia
      lining the caecum and colon. This staining intensity was markedly increased in
      pectin-fed rats, along with the appearance of strong reactivity for MCT1 on the
      apical membranes of the surface and crypt epithelia of caecum and colon. Our
      results also showed that MCT1 co-localizes with its chaperone, basigin (CD147),
      in the rat gastrointestinal tract, and that the pectin feeding increased the
      expression of CD147. In vivo functional studies revealed an enhanced acetate
      absorption in the colon of pectin-fed in comparison with control animals. We
      conclude that MCT1 is up-regulated along the gastrointestinal tract of pectin-fed
      rats, which might represent an adaptive response to the increased availability of
      its substrates.

PMID- 19168541
TI  - Organization of ventricular fibrillation in the human heart: experiments and
      models.
AB  - Sudden cardiac death is a major health problem in the industrialized world. The
      lethal event is typically ventricular fibrillation (VF), during which the co
      ordinated regular contraction of the heart is overthrown by a state of mechanical
      and electrical anarchy. Understanding the excitation patterns that sustain VF is
      important in order to identify potential therapeutic targets. In this paper, we
      studied the organization of human VF by combining clinical recordings of
      electrical excitation patterns on the epicardial surface during in vivo human VF
      with simulations of VF in an anatomically and electrophysiologically detailed
      computational model of the human ventricles. We find both in the computational
      studies and in the clinical recordings that epicardial surface excitation
      patterns during VF contain around six rotors. Based on results from the simulated
      three-dimensional excitation patterns during VF, which show that the total number
      of electrical sources is 1.4 +/- 0.12 times greater than the number of epicardial
      rotors, we estimate that the total number of sources present during clinically
      recorded VF is 9.0 +/- 2.6. This number is approximately fivefold fewer compared
      with that observed during VF in dog and pig hearts, which are of comparable size
      to human hearts. We explain this difference by considering differences in action
      potential duration dynamics across these species. The simpler spatial
      organization of human VF has important implications for treatment and prevention
      of this dangerous arrhythmia. Moreover, our findings underline the need for
      integrated research, in which human-based clinical and computational studies
      complement animal research.

PMID- 19168542
TI  - Plasma and peritoneal concentration following continuous infusion of cefotaxime
      in patients with secondary peritonitis.
AB  - OBJECTIVES: The aim of this study was to determine the steady-state plasma and
      peritoneal concentrations of cefotaxime and its metabolite desacetyl-cefotaxime
      administered by continuous infusion to critically ill patients with secondary
      peritonitis. PATIENTS AND METHODS: In 11 patients, a continuous infusion of 4
      g/24 h of cefotaxime following a bolus of 2 g was evaluated. Plasma and
      peritoneal levels of cefotaxime and desacetyl-cefotaxime were measured at steady
      state on days 2 and 3 (plasma) and on day 3 (peritoneal) by HPLC. Results are
      expressed as means +/- SD. RESULTS: Total and unbound plasma levels of cefotaxime
      were 24.0 +/- 21.5 and 20.3 +/- 19.8 mg/L on day 2 and 22.1 +/- 20.7 and 18.9 +/-
      19.2 mg/L on day 3, respectively. Total and unbound levels of cefotaxime in the
      peritoneal fluids were 16.2 +/- 11.5 and 14.3 +/- 10.4 mg/L, respectively. The
      unbound fraction of plasma cefotaxime was 81.8 +/- 5.9% on day 2 and 82.6 +/-
      7.7% on day 3, and the unbound fraction at the peritoneal site was 87.0 +/- 5.5%
      on day 3. Total and unbound plasma levels of desacetyl-cefotaxime were 9.0 +/-
      8.1 and 8.4 +/- 8.1 mg/L on day 2 and 7.6 +/- 7.6 and 7.2 +/- 7.6 mg/L on day 3,
      respectively. Total and unbound levels of desacetyl-cefotaxime in the peritoneal
      fluids were 11.9 +/- 11.5 and 10.9 +/- 10.8 mg/L, respectively. The MICs for the
      enterobacteria recovered ranged from 0.016 to 0.25 mg/L. CONCLUSIONS: Continuous
      infusion of 4 g/24 h of cefotaxime provided a peritoneal concentration >5x MIC
      for the recovered Enterobacteriaceae and the susceptibility breakpoint of
      cefotaxime for facultative Gram-negative bacilli.

PMID- 19168543
TI  - Influence of liver fibrosis stage on plasma levels of efavirenz in HIV-infected
      patients with chronic hepatitis B or C.
AB  - OBJECTIVES: Liver function is a key component of efavirenz metabolism and might
      be altered in severe liver fibrosis induced by HIV/chronic hepatitis co
      infection. However, data evaluating the impact of liver fibrosis stages on the
      plasma efavirenz level are lacking. PATIENTS AND METHODS: In this study,
      conducted in 134 HIV-infected patients [77, 35 and 22 HIV mono-infected,
      HIV/hepatitis C virus (HCV) co-infected and HIV/hepatitis B virus (HBV) co
      infected, respectively] treated with efavirenz 600 mg once a day in combination
      with other antiretroviral agents, plasma concentration was measured at least 8 h
      after the last drug intake using a validated HPLC method. The degree of liver
      fibrosis was determined by means of either liver biopsy or non-invasive
      biochemical markers (Fibrotest. The proportions of patients above a threshold of
      4000 ng/mL were compared by means of Pearson's chi(2) test or Fisher's exact
      test. RESULTS: In HIV mono-infected and HIV/HCV and HIV/HBV co-infected patients,
      mean +/- SD efavirenz plasma concentrations were 3060 +/- 1928, 4108 +/- 3324 and
      3163 +/- 2432 ng/mL, respectively. The proportion of patients with an efavirenz
      concentration above 4000 ng/mL differed significantly according to the presence
      of hepatitis and the fibrosis stage. A concentration above 4000 ng/mL was found
      in 14 patients (18.2%) mono-infected with HIV compared with 5 (22.7%, P = 0.01)
      and 9 (25.7%, P = 0.001) HIV/HBV or HIV/HCV co-infected patients, respectively.
      When the fibrosis stage was considered in all patients with hepatitis, 3
      cirrhotic patients (42.6%) had an efavirenz concentration above the 4000 ng/mL
      threshold [compared with 14 (18.2%) HIV mono-infected patients, P = 0.001].
      CONCLUSIONS: Therapeutic drug monitoring may be of interest in cirrhotic patients
      more at risk of side effects due to efavirenz overdosing.

PMID- 19168544
TI  - Deletion of eIF2beta suppresses testicular cancer incidence and causes recessive
      lethality in agouti-yellow mice.
AB  - The agouti-yellow (A(y)) deletion is the only genetic modifier known to suppress
      testicular germ cell tumor (TGCT) susceptibility in mice or humans. The A(y)
      mutation deletes Raly and Eif2s2, and induces the ectopic expression of agouti,
      all of which are potential TGCT-modifying mutations. Here we report that the
      reduced TGCT incidence of heterozygous A(y) males and the recessive embryonic
      lethality of A(y) are caused by the deletion of Eif2s2, the beta subunit of
      translation initiation factor eIF2. We found that the incidence of affected males
      was reduced 2-fold in mice that were partially deficient for Eif2s2 and that
      embryonic lethality occurred near the time of implantation in mice that were
      fully deficient for Eif2s2. In contrast, neither reduced expression of Raly in
      gene-trap mice nor ectopic expression of agouti in transgenic or viable-yellow
      (A(vy)) mutants affected TGCT incidence or embryonic viability. In addition, we
      provide evidence that partial deficiency of Eif2s2 attenuated germ cell
      proliferation and differentiation, both of which are important to TGCT formation.
      These results show that germ cell development and TGCT pathogenesis are sensitive
      to the availability of the eIF2 translation initiation complex and to changes in
      the rate of translation.

PMID- 19168545
TI  - The highly conserved NANOS2 protein: testis-specific expression and significance
      for the human male reproduction.
AB  - The highly conserved Nanos gene was found to encode a translational repressor
      necessary for germ-cell development in lower organisms. The mammalian homologue,
      Nanos2, was recently found to be expressed in the mouse germ cells. Since its
      disruption caused infertility exclusively in males, we sought to study the
      significance of this gene in human male reproduction. Here, we describe for the
      first time the expression pattern of the NANOS2 gene in human tissues and show
      that it is testis specific. We found that NANOS2 protein is present in prenatal
      germ cells and at later stages in spermatogenesis. To elucidate the role of
      NANOS2 in human germ-line development, we screened this gene for mutations in 214
      males with isolated sterility and spermatogenic abnormalities. We identified two
      heterozygous variants, each in a different oligospermic patient, the second
      allele being the wild-type. The influence of the first variant, a missense
      mutation H68Q on the sterility phenotype, was not obvious since it was
      accompanied by a microdeletion within the AZF region of the Y chromosome. The
      second variant contained a silent mutation, H109H. Although both mutations were
      situated within the most conserved RNA-binding domain and were absent in 400
      fertile males, it is not obvious that they cause male infertility.

PMID- 19168546
TI  - The SNARE-associated component SNAPIN binds PUMILIO2 and NANOS1 proteins in human
      male germ cells.
AB  - It has been reported that a highly conserved human protein PUMILIO2 forms a
      complex with NANOS1 in human male germ cells, as does the Drosophila ancestor
      Pumilio, which binds Nanos to regulate translation of specific mRNAs. Here, we
      found that PUMILIO2 interacts also with SNAPIN, a modulator of SNARE complex
      assembly, which is involved in vesicle trafficking. We demonstrated that SNAPIN
      interacts additionally with NANOS1 protein. This is the first report
      demonstrating that the N-terminal region of NANOS1 is necessary for protein
      binding. In human testis, SNAPIN co-localizes with PUMILIO2 and NANOS1 in
      prenatal and also in spermatogenic germ cells of the adult. We describe for the
      first time the expression of SNAPIN in germ cells which raises possibility that
      SNAPIN plays an extra role in mammals which is germ cell specific. The presence
      of a coiled-coil domain responsible for protein-protein interaction could enable
      SNAPIN to be an adaptor of PUMILIO2 and NANOS1, binding other factors to regulate
      translation in the development of the human germ cells.

PMID- 19168547
TI  - Glomerular filtration rate in children with chronic kidney disease.

PMID- 19168548
TI  - Assessing thrombin generation at the point of care.

PMID- 19168549
TI  - Estimating equations for glomerular filtration rate in children: laboratory
      considerations.

PMID- 19168550
TI  - Counterpoint: legitimate and illegitimate tests of free-analyte assay function:
      we need to identify the factors that influence free-analyte assay results.

PMID- 19168551
TI  - New antibody assays for cardiovascular disease: future tools for the clinical
      chemist?

PMID- 19168552
TI  - Apolipoprotein B and cardiovascular disease risk: position statement from the
      AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices.
AB  - BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) has been the cornerstone
      measurement for assessing cardiovascular risk for nearly 20 years. CONTENT:
      Recent data demonstrate that apolipoprotein B (apo B) is a better measure of
      circulating LDL particle number (LDL-P) concentration and is a more reliable
      indicator of risk than LDL-C, and there is growing support for the idea that
      addition of apo B measurement to the routine lipid panel for assessing and
      monitoring patients at risk for cardiovascular disease (CVD) would enhance
      patient management. In this report, we review the studies of apo B and LDL-P
      reported to date, discuss potential advantages of their measurement over that of
      LDL-C, and present information related to standardization. CONCLUSIONS: In line
      with recently adopted Canadian guidelines, the addition of apo B represents a
      logical next step to National Cholesterol Education Program Adult Treatment Panel
      III (NCEP ATPIII) and other guidelines in the US. Considering that it has taken
      years to educate physicians and patients regarding the use of LDL-C, changing
      perceptions and practices will not be easy. Thus, it appears prudent to consider
      using apo B along with LDL-C to assess LDL-related risk for an interim period
      until the superiority of apo B is generally recognized.

PMID- 19168553
TI  - Disposition of MDMA and metabolites in human sweat following controlled MDMA
      administration.
AB  - BACKGROUND: Understanding the excretion of 3,4-methylenedioxymethamphetamine
      (MDMA) and metabolites in sweat is vital for interpretation of sweat tests in
      drug treatment, criminal justice, and workplace programs. METHODS: Placebo, low
      (1.0 mg/kg), and high (1.6 mg/kg) doses of oral MDMA were given double-blind in
      random order to healthy volunteers (n = 15) with histories of MDMA use.
      Participants resided on the closed clinical research unit for up to 7 days after
      each dose. Volunteers wore PharmChek sweat patches (n = 640) before, during, and
      after controlled dosing. Patches were analyzed by solid phase extraction and GC
      MS for MDMA, methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxyamphetamine
      (HMA), and 4-hydroxy-3-methoxymethamphetamine (HMMA). Limits of quantification
      (LOQ) were 2.5 ng/patch for MDMA and 5 ng/patch for HMA, HMMA, and MDA. RESULTS:
      MDMA was the primary analyte detected in 382 patches (59.7%), with concentrations
      up to 3007 ng/patch. MDA was detected in 188 patches (29.4%) at <172 ng/patch,
      whereas no HMMA or HMA was detected; 224 patches (35.0%) and 60 patches (9.4%)
      were positive for MDMA and MDA, respectively, at the 25-ng/patch threshold
      proposed by the Substance Abuse and Mental Health Services Administration.
      CONCLUSIONS: Sweat testing was shown to be an effective and reliable method for
      monitoring MDMA use in this controlled MDMA administration study. However,
      variability in sweat excretion suggests that results should be interpreted
      qualitatively rather than quantitatively. These data provide a scientific
      database for interpretation of MDMA sweat test results.

PMID- 19168554
TI  - Automated determination of serum alpha1-antitrypsin by antitryptic activity
      measurement.
AB  - BACKGROUND: Alpha1-Antitrypsin (A1AT) deficiency is currently detectable by
      protein immunoassay, phenotyping, and genotyping of the S and Z mutations, but no
      fully automated method for standard biochemical analyzers is yet available. Here,
      we present a method that measures the antitryptic activity in serum. This method
      is rapid, automated, and allows the easy evaluation of a large cohort of
      patients. METHODS: Our automated assay involves determining serum antitryptic
      capacity on the Olympus AU 400 autoanalyzer by using trypsin and succinylated
      gelatin as substrate in the presence of trinitrobenzene sulfonic acid. The
      results are expressed as a percentage of inhibition of the reaction of trypsin
      with succinylated gelatin. After we performed analytical validation studies and
      reference-interval determination based on serum samples from 120 healthy persons,
      we tested the assay on deidentified samples from 120 patients with various
      pathologies (primarily pulmonary) of unexplained origin and normal A1AT
      concentrations and phenotypes. RESULTS: The analysis rate was up to 120 samples
      per hour. Intraassay CVs ranged from 3.1%-16.2%, and interassay CV was 7.5%. The
      reference population showed mean (SD) 58.4 (6.7)% inhibition. The detection limit
      was 9.5% inhibition. The 120 studied patients displayed significantly lower mean
      activity than 120 healthy individuals (P < 0.0001). CONCLUSION: This assay is
      stable, reliable, and easily automated by use of open-system analyzers, allowing
      for the rapid evaluation of patients. After further validation on a larger
      randomized cohort, this new approach should function as a useful method to
      explore A1AT deficiency, especially in large-scale studies.

PMID- 19168555
TI  - Prime time for enzymatic creatinine methods in pediatrics.
AB  - BACKGROUND: The literature regarding the nonspecificity of applications of the
      Jaffe (alkaline picrate) reaction for creatinine is generally outdated. We
      conducted a specificity study to update the nonspecificity information for
      current Jaffe and enzymatic creatinine assays. METHODS: Two serum pools with
      creatinine concentrations within the pediatric reference interval were spiked
      with albumin, IgG, unconjugated bilirubin, adult hemoglobin (Hb A), and fetal
      hemoglobin (Hb F) to produce 1 unspiked and 5 spiked samples per pool. The 35
      laboratories participating in the survey used a total of 14 method-analyzer
      combinations. Measurements were performed in triplicate in a single run in
      accordance with manufacturer instructions. Absolute differences in creatinine
      concentration between spiked and unspiked samples were calculated per laboratory.
      Mixed ANOVA was used to quantify the interferent-related CV component for the
      Jaffe and enzymatic methods. RESULTS: The interference by bilirubin and Hb A on
      serum creatinine measurements was <10% for most of the Jaffe and enzymatic
      methods. Obvious interference was observed among the Jaffe methods in samples
      spiked with Hb F, albumin, and IgG, but not among the enzymatic methods. The
      within-laboratory interferent-related CVs for the Jaffe method-analyzer
      combinations ranged from 8.0%-27% at a creatinine concentration of 40.4
      micromol/L (0.46 mg/dL) and from 5.4%-15% at 73.4 micromol/L (0.83 mg/dL).
      Enzymatic methods had within-laboratory interferent-related CVs of <4% at both
      concentrations. CONCLUSIONS: Albumin, IgG, and Hb F interfered with Jaffe
      creatinine assays, leading to inaccuracies in estimated glomerular filtration
      rates that are clinically important, especially in children and neonates. Because
      protein error and Hb F interference do not occur with any of the enzymatic
      methods tested, we conclude that enzymatic creatinine methods are preferred for
      evaluation of kidney function in pediatric cases.

PMID- 19168556
TI  - Reducing routine ionized calcium measurement.
AB  - BACKGROUND: Ionized calcium (iCa) is measured frequently in hospitalized
      patients, and hypocalcemia is frequently found, seemingly supporting the
      practice. METHODS: We retrieved the results of 58 040 iCa tests and records of
      intravenous (IV) and oral calcium supplementation from laboratory and hospital
      information systems and evaluated them for frequency of testing, frequency of
      hypocalcemia, and effects of calcium supplementation. RESULTS: Serial and daily
      iCa testing was common and responsible for a substantial fraction of all iCa
      tests ordered. Half of all patients tested had iCa values below the reference
      interval. IV, but not oral, calcium therapy increased mean iCa concentrations,
      but the effect of calcium administration was small compared with the spontaneous
      increase in iCa that occurred in similar patients who received no calcium
      treatment. A retrospective analysis suggested that a low total calcium (tCa)
      concentration (<2.00 mmol/L, <8 mg/dL) could identify most patients with low iCa
      (<1.0 mmol/L). Introduction of a reflexive strategy reduced iCa testing by 72%
      76% and reduced IV calcium gluconate therapy by 45%-81%. CONCLUSIONS: Testing for
      iCa and IV calcium supplementation were significantly reduced with a reflexive
      calcium testing strategy that provided iCa testing only to patients with low tCa.
      Adverse clinical outcomes possibly associated with hypocalcemia did not increase.

PMID- 19168557
TI  - Analytic and clinical utility of a next-generation, highly sensitive cardiac
      troponin I assay for early detection of myocardial injury.
AB  - BACKGROUND: Improvements in cardiac troponin (cTn) assays have increased the
      rapidity with which clinicians can identify patients with changing cTn
      concentrations (rise or fall) indicative of acute myocardial injury. The aim of
      the present study was to characterize a new, high-sensitivity cTnI (hs-cTnI)
      assay and examine whether increased sensitivity can result in still earlier
      detection of evolving injury. METHODS: We determined the limit of detection,
      precision profiles, and preliminary estimates of the 99th percentile for the
      Beckman Coulter hs-cTnI assay in 125 healthy individuals (age <55 years, 54%
      male). We compared AccuTnI and hs-cTnI to assess whether change criteria for
      early concentration changes (i.e., > or =3SD for low concentrations and 20%
      difference for concentrations >0.10 microg/L) were exceeded in the first 2
      specimens (median time between specimens, 1 h; 25th-75th percentile, 1-3 h) from
      subjects with symptoms suggestive of cardiac ischemia (n = 290). RESULTS: The
      limit of detection for the hs-cTnI assay was 2.06 ng/L, and the 20% CV and 10% CV
      concentrations were 2.95 and 8.66 ng/L, respectively. The preliminary 99th
      percentile estimates in lithium heparin, serum, and EDTA plasma were 9.20, 8.00,
      and 8.60 ng/L, respectively. In 108 patients with myocardial injury based on the
      peak AccuTnI concentration, applying the change criteria on the 2 earliest
      specimens identified 81% (95% CI 73%-88%) of patients using the hs-cTnI assay
      compared to 62% (53%-71%) using the AccuTnI assay (P < 0.001). CONCLUSIONS:
      Although more extensive validation studies are required, this Beckman Coulter hs
      cTnI assay appears to detect patients with evolving myocardial injury earlier.

PMID- 19168558
TI  - Processing of pro-brain natriuretic peptide is suppressed by O-glycosylation in
      the region close to the cleavage site.
AB  - BACKGROUND: Processing of the brain natriuretic peptide (BNP) precursor, proBNP,
      is a convertase-dependent reaction that produces 2 molecules--the active BNP
      hormone and the N-terminal part of proBNP (NT-proBNP). Although proBNP was first
      described more than 15 years ago, very little is known about the cellular
      mechanism of its processing. The study of proBNP processing mechanisms is
      important, because processing impairments could be associated with the
      development of heart failure (HF). METHODS: The biochemical properties of
      recombinant proBNP and NT-proBNP and the same molecules derived from the blood of
      HF patients were analyzed by gel-filtration chromatography, site-directed
      mutagenesis, and different immunochemical methods with a panel of monoclonal
      antibodies (MAbs). RESULTS: Part of the proBNP molecule (amino acid residues 61
      76) located near the cleavage site was inaccessible to specific MAbs because of
      the presence of O-glycans, whereas the same region in NT-proBNP was completely
      accessible. We demonstrated that a convertase (furin) could effectively cleave
      deglycosylated (but not intact) proBNP. Of several mutant proBNP forms produced
      in a HEK 293 cell line, only the T71A variant was effectively processed in the
      cell. CONCLUSIONS: Only proBNP that was not glycosylated in the region of the
      cleavage site could effectively be processed into BNP and NT-proBNP. Site
      directed mutagenesis enabled us to ascertain the unique suppressing role of T71
      bound O-glycan in proBNP processing.

PMID- 19168559
TI  - High-sensitivity chemiluminescence immunoassays for detection of growth hormone
      doping in sports.
AB  - BACKGROUND: Recombinant human growth hormone (rhGH) is abused in sports, but
      adequate routine doping tests are lacking. Analysis of serum hGH isoform
      composition has been shown to be effective in detecting rhGH doping. We developed
      and validated selective immunoassays for isoform analysis with potential utility
      for screening and confirmation in doping tests. METHODS: Monoclonal antibodies
      with preference for pituitary hGH (phGH) or rhGH were used to establish 2 pairs
      of sandwich-type chemiluminescence assays with differential recognition of rhGH
      (recA and recB) and phGH (pitA and pitB). We analyzed specimens from volunteers
      before and after administration of rhGH and calculated ratios between the
      respective rec- and pit-assay results. RESULTS: Functional sensitivities were
      <0.05 microg/L, with intra- and interassay imprecision < or =8.4% and < or
      =13.7%, respectively. In 2 independent cohorts of healthy subjects, rec/pit
      ratios (median range) were 0.84 (0.09-1.32)/0.81 (0.27-1.21) (recA/pitA) and 0.68
      (0.08-1.20)/0.80 (0.25-1.36) (recB/pitB), with no sex difference. In 20
      recreational athletes, ratios (median SD) increased after a single injection of
      rhGH, reaching 350% (73%) (recA/pitA) and 400% (93%) (recB/pitB) of baseline
      ratios. At a moderate dose (0.033 mg/kg), mean recA/pitA and recB/pitB ratios
      remained significantly increased for 18 h (men) and 26 h (women). After high-dose
      rhGH (0.083 mg/kg), mean rec/pit ratios remained increased for 32 h (recA/pitA)
      and 34 h (recB/pitB) in men and were still increased after 36 h in women.
      CONCLUSIONS: Using sensitive chemiluminescence assays with preferential
      recognition of phGH or rhGH, detection of a single injection of rhGH was possible
      for up to 36 h.

PMID- 19168560
TI  - Comparison of immunoassays for the selective measurement of human high-molecular
      weight adiponectin.
AB  - BACKGROUND: Adiponectin is an adipocyte-derived hormone circulating in different
      multimer complexes. The high-molecular-weight (HMW) complex is likely the active
      form of this protein and has been recognized as a risk marker for type 2 diabetes
      and coronary artery disease (CAD). Because quantification of HMW adiponectin by
      Western blot analysis is time-consuming, novel ELISAs have been developed to
      simplify measurements in clinical research. However, these enzyme immunoassays
      have not been cross-validated in larger patient groups. We evaluated 2 individual
      ELISA systems by comparison to Western blotting for measurement of the
      distribution of HMW adiponectin in healthy individuals and patients with CAD and
      type 2 diabetes. METHODS: We measured HMW adiponectin in 204 individuals (83 CAD
      patients, 81 type 2 diabetes patients, and 40 healthy controls). Correlations,
      range of agreement, and imprecision of HMW concentrations obtained using 2
      commercial ELISAs (#1, ALPCO Diagnostics; #2, Millipore) were evaluated by
      comparison with quantitative Western blotting. RESULT: Adiponectin results of the
      ELISAs were significantly correlated with those obtained by Western blotting
      (both r > 0.75, P < 0.001). Deming regression and Bland-Altman analyses indicated
      high agreement among the 3 immunoassays. The median difference between HMW
      adiponectin concentrations measured by ELISA and by Western blot was +0.4 mg/L
      for ELISA #1 and -0.4 mg/L for ELISA #2 with 95% of value differences <3 mg/L.
      CONCLUSIONS: Selective measurement of HMW adiponectin by ELISA is feasible;
      however, individual differences among immunoassays must be considered. The
      evaluated ELISAs exhibit analytical characteristics that allow their use as
      equivalent for Western blot analysis in larger clinical and epidemiological
      groups.

PMID- 19168561
TI  - Massive pericarditis constrictiva calcarea with compression of the right
      ventricle and consecutive pulmonary embolism.
AB  - A 40-year-old man was admitted with a massive pericarditis constrictiva calcarea.
      Transthoracic and transoesophageal echocardiography demonstrated a double-layered
      pericardial calcification with interspacial effusion, a massive compression of
      the right ventricle, and a thrombus formation in the ventricle. In addition,
      severe pulmonary embolism due to this right ventricular thrombus formation was
      diagnosed by CT. This case demonstrates the importance of a multimodal imaging
      approach (echocardiography, TDI, MRI, CT) in the diagnosis of constrictive
      pericarditis and pericardial masses. In respect to the severe pericardial
      calcification with the massive interspacial mass, and the compression of the
      right ventricle with thrombus formation and consecutive pulmonary embolism, this
      case appears to be a very rare and uncommon clinical finding.

PMID- 19168562
TI  - The missing leak: a case report of a baffle-leak closure using real-time 3D
      transoesophageal guidance.
AB  - Brady-arrhythmias in patients undergone atrial switch procedures (Mustard or
      Senning procedure) for complete transposition of the great arteries (TGA) are
      common and often require implantation of permanent pacemakers. It has been shown
      that in patients with palliated congenital cardiac defects with residual intra
      cardiac shunts, permanent pacemaker implantation is associated with an increased
      risk of thrombo-embolism. Patients with TGA and concomitant baffle leaks may have
      an even further increased thrombo-embolic risk, given that the leaks can provide
      the conduit for venous to systemic thrombo-embolism. In order to decrease this
      risk, all TGA patients who require pacemaker implantation typically undergo a
      thorough pre-procedural evaluation to assess for the presence of a baffle leak.
      Traditional imaging modalities, however, are often limited in their ability to
      detect and/or properly locate small baffle leaks. We report a case of a patient
      with TGA and a baffle leak that was both identified and percutaneously closed
      with the assistance of real-time 3D transoesophageal echocardiography.

PMID- 19168564
TI  - Selection on nuclear genes in a Pinus phylogeny.
AB  - In this study, we investigate natural selection in a pine phylogeny. DNA
      sequences from 18 nuclear genes were used to construct a very well-supported
      species tree including 10 pine species. This tree is in complete agreement with a
      previously reported supertree constructed from morphological and molecular data,
      but there are discrepancies with previous chloroplast phylogenies within the
      section Pinus. A significant difference in evolutionary rate between Picea and
      Pinus was found, which could potentially indicate a lower mutation rate in Picea,
      but other scenarios are also possible. Several approaches were used to study
      selection patterns in a set of 21 nuclear genes in pines and in some cases in
      Picea and Pseudotsuga. The overall pattern suggests efficient purifying selection
      resulting in low branch-specific d(n)/d(s) ratios with an average of 0.22, which
      is similar to other higher plants. Evidence for purifying selection was common
      and found on at least 55% of the branches. Evidence of positive selection at
      several sites was found in a phytocyanin homolog and significant differences in
      d(n)/d(s) among the branches in the gene tree in dehydrin 1. Several genes
      suitable for further phylogenetic analysis at various levels of divergence were
      identified.

PMID- 19168563
TI  - Aequorin variants with improved bioluminescence properties.
AB  - The photoprotein aequorin has been widely used as a bioluminescent label in
      immunoassays, for the determination of calcium concentrations in vivo, and as a
      reporter in cellular imaging. It is composed of apoaequorin (189 amino acid
      residues), the imidazopyrazine chromophore coelenterazine and molecular oxygen.
      The emission characteristics of aequorin can be changed by rational design of the
      protein to introduce mutations in its structure, as well as by substituting
      different coelenterazine analogues to yield semi-synthetic aequorins. Variants of
      aequorin were created by mutating residues His16, Met19, Tyr82, Trp86, Trp108,
      Phe113 and Tyr132. Forty-two aequorin mutants were prepared and combined with 10
      different coelenterazine analogues in a search for proteins with different
      emission wavelengths, altered decay kinetics and improved stability. This
      spectral tuning strategy resulted in semi-synthetic photoprotein mutants with
      significantly altered bioluminescent properties.

PMID- 19168565
TI  - Phylogeographic analyses and paleodistribution modeling indicate pleistocene in
      situ survival of Hordeum species (Poaceae) in southern Patagonia without genetic
      or spatial restriction.
AB  - Although many phylogeographic studies have been conducted to analyze the impact
      of the ice age on species history of Northern Hemisphere mountain plants, such
      studies are nearly absent for plants of the Southern Hemisphere, particularly for
      lowland vegetation units. These species should have been primarily influenced by
      climate cooling and changes in precipitation regime instead of glaciers covering
      their distribution areas. It is thought that New World lowland species generally
      evaded climate changes by equatorial migration during Pleistocene cold cycles and
      recolonized their habitats at higher latitudes when climate warmed up again. In
      contrast to Eurasia, latitudinal orientation of the major mountain ranges in the
      Americas made these migrations easily possible. In the huge steppe of the
      Patagonian plains and adjacent Andes of southern South America thrives a group of
      three sympatrically distributed diploid species of the barley genus Hordeum,
      which originated during the last 1.3 million years (My) from a common progenitor.
      To get insights into the speciation mode of the taxa and to test the hypothesis
      of longitudinal migration of steppe vegetation during the Pleistocene, we
      conducted population genetic and phylogeographic analyses based on sequences of
      the chloroplast trnL-F region from 922 individuals. We found a high number of
      chloroplast haplotypes shared among species, which indicate speciation through
      vicariance events. Analysis of the distribution of genetic diversity within and
      among species inferred an origin of Hordeum comosum in the Central Argentine
      Andes, whereas Hordeum patagonicum and Hordeum pubiflorum originated in southern
      Patagonia. The extant occurrence of H. comosum in southern Patagonia and H.
      pubiflorum northward along the Argentine Andes was caused by reciprocal migration
      after the origin of the species. Surprisingly, molecular data provided no
      evidence for range shifts toward the north during the last glacial maximum and
      recolonization of southerly habitats afterward, but indicated in situ survival of
      large populations of Hordeum species within their extant distribution ranges even
      in southernmost Patagonia and Tierra del Fuego. Ecoclimatic niche modeling used
      to reconstruct the potential paleodistribution areas of the species during the
      last glacial maximum shows that climate conditions were sufficient for the
      species to survive Pleistocene cold cycles in Patagonia without significant
      geographic restrictions. Molecular data together with ecological niche modeling
      indicate stable geographic distribution areas in two of the three species for at
      least the Holocene. As the Hordeum species are characteristic taxa of different
      steppe habitats, we speculate that the Patagonian steppe might be an old
      vegetation unit occurring for up to 4.5 My in southern South America.

PMID- 19168566
TI  - Comparative analysis of structural diversity and sequence evolution in plant
      mitochondrial genes transferred to the nucleus.
AB  - The transfer of functional mitochondrial genes to the nucleus is an ongoing
      process during plant evolution that has made a major impact on cytonuclear
      interactions and mitochondrial genome evolution. Analysis of evolutionarily
      recent transfers in plants provides insights into the evolutionary dynamics of
      the process and how transferred genes become functional in the nucleus. Here, we
      report 42 new transferred genes in various angiosperms, including 9 separate
      transfers of the succinate dehydrogenase gene sdh3. We performed comparative
      analyses of gene structures and sequence evolution of 77 genes transferred to the
      nucleus in various angiosperms, including multiple transfers of 10 genes in
      different lineages. Many genes contain mitochondrial targeting presequences, and
      potentially 5' cis-regulatory elements, that were acquired from pre-existing
      nuclear genes for mitochondrial proteins to create chimeric gene structures. In
      eight separate cases, the presequence was acquired from either the hsp70
      chaperonin gene or the hsp22 chaperonin gene. The most common location of introns
      is in the presequence, and the least common is in the region transferred from the
      mitochondrion. Several genes have an intron between the presequence and the core
      region, or an intron in the 5'UTR (untranslated region) or 3'UTR, suggesting
      presequence and/or regulatory element acquisition by exon shuffling. Both
      synonymous and nonsynonymous substitution rates have increased considerably in
      the transferred genes compared with their mitochondrial counterparts, and the
      degree of rate acceleration varies by gene, species, and evolutionary timing of
      transfer. Pairwise and branchwise K(a)/K(s) analysis identified four genes with
      evidence for positive selection, but positive selection is generally uncommon in
      transferred genes. This study provides a detailed portrayal of structural and
      sequence evolution in mitochondrial genes transferred to the nucleus, revealing
      the frequency of different mechanisms for how presequences and introns are
      acquired and showing how the sequences of transferred genes evolve after movement
      between cellular genomes.

PMID- 19168567
TI  - Congruent evolution of genetic and environmental robustness in micro-RNA.
AB  - Genetic robustness, the preservation of an optimal phenotype in the face of
      mutations, is critical to the understanding of evolution as phenotypically
      expressed genetic variation is the fuel of natural selection. The origin of
      genetic robustness, whether it evolves directly by natural selection or it is a
      correlated byproduct of other phenotypic traits, is, however, unresolved.
      Examining micro-RNA (miRNA) genes of several eukaryotic species, Borenstein and
      Ruppin (Borenstein E, Ruppin E. 2006. Direct evolution of genetic robustness in
      microRNA. Proc Natl Acad Sci USA. 103: 6593) showed that the structure of miRNA
      precursor stem loops exhibits significantly increased mutational robustness in
      comparison with a sample of random RNA sequences with the same stem-loop
      structure. The observed robustness was found to be uncorrelated with traditional
      measures of environmental robustness-implying that miRNA sequences show evidence
      of the direct evolution of genetic robustness. These findings are surprising as
      theoretical results indicate that the direct evolution of robustness requires
      high mutation rates and/or large effective population sizes only found among RNA
      viruses, not multicellular eukaryotes. We demonstrate that the sampling method
      used by Borenstein and Ruppin introduced significant bias that lead to an
      overestimation of robustness. Introducing a novel measure of environmental
      robustness based on the equilibrium thermodynamic ensemble of secondary
      structures of the miRNA precursor sequences, we demonstrate that the biophysics
      of RNA folding induces a high level of correlation between genetic (mutational)
      and environmental (thermodynamic) robustness, as expected from the theory of
      plastogenetic congruence introduced by Ancel and Fontana (Ancel LW, Fontana W.
      2000. Plasticity, evolvability, and modularity in RNA. J Exp Zool. 288: 242-283).
      In light of theoretical considerations, we believe that this correlation strongly
      suggests that genetic robustness observed in miRNA sequences is the byproduct of
      selection for environmental robustness.

PMID- 19168568
TI  - Transgenic expression of aflatoxin aldehyde reductase (AKR7A1) modulates
      aflatoxin B1 metabolism but not hepatic carcinogenesis in the rat.
AB  - In both experimental animals and humans, aflatoxin B(1) (AFB(1)) is a potent
      hepatic toxin and carcinogen against which a variety of antioxidants and
      experimental or therapeutic drugs (e.g., oltipraz, related dithiolethiones, and
      various triterpenoids) protect from both acute toxicity and carcinogenesis. These
      agents induce several hepatic glutathione S-transferases (GST) as well as aldo
      keto reductases (AKR) which are thought to contribute to protection. Studies were
      undertaken in transgenic rats to examine the role of one inducible enzyme,
      AKR7A1, for protection against acute and chronic actions of AFB(1) by enhancing
      detoxication of a reactive metabolite, AFB(1) dialdehyde, by reduction to
      alcohols. The AFB(1) dialdehyde forms adducts with protein amino groups by a
      Schiff base mechanism and these adducts have been theorized to be at least one
      cause of the acute toxicity of AFB(1) and to enhance carcinogenesis. A liver
      specific AKR7A1 transgenic rat was constructed in the Sprague-Dawley strain and
      two lines, AKR7A1(Tg2) and AKR7A1(Tg5), were found to overexpress AKR7A1 by 18-
      and 8-fold, respectively. Rates of formation of AFB(1) alcohols, both in hepatic
      cytosols and as urinary excretion products, increased in the transgenic lines
      with AKR7A1(Tg2) being the highest. Neither line offered protection against acute
      AFB(1)-induced bile duct proliferation, a functional assessment of acute
      hepatotoxicity by AFB(1), nor did they protect against the formation of GST-P
      positive putative preneoplastic foci as a result of chronic exposure to AFB(1).
      These results imply that the prevention of protein adducts mediated by AKR are
      not critical to protection against AFB(1) tumorigenicity.

PMID- 19168570
TI  - Pragmatic challenges for the vision of toxicity testing in the 21st century in a
      regulatory context: another Ames test? ...or a new edition of "the Red Book"?

PMID- 19168569
TI  - Arsenic activates EGFR pathway signaling in the lung.
AB  - Arsenic is an established lung carcinogen, however, the carcinogenic mechanisms
      are currently under investigation. Phosphorylation of the epidermal growth factor
      receptor (EGFR) has been reported with arsenic exposure in bladder cells. EGFR is
      a tyrosine kinase transmembrane receptor that regulates important processes in
      carcinogenesis, including cell survival, cell cycle progression, tumor invasion,
      and angiogenesis. We investigated the mechanisms of EGFR pathway activation by
      levels of arsenic relevant to human exposure scenarios both in vitro using
      cultured lung epithelial cells, and in lung tumors samples from New England Lung
      Cancer Study participants. Toenail arsenic levels were used as an internal
      biomarker of arsenic exposure. Our in vitro data suggest that arsenic increases
      levels of the EGFR ligand, heparin binding-EGF, and activate EGFR phosphorylation
      in the lung. Downstream of EGFR, arsenic exposure increased pERK and cyclin D1
      levels. These effects were inhibited by treatment of cultured cells with the EGFR
      tyrosine kinase inhibitor, Tarceva (erlotinib). In a consecutive series of human
      lung tumor specimens, pEGFR protein levels were higher in subjects with elevated
      toenail arsenic levels compared to those with low exposure (odds ratio adjusted
      for other factors, OR 4.1 (95% confidence interval 1.1-15.6) (p = 0.04). These
      data suggest that arsenic exposure may stimulate EGFR pathway activation in the
      lung. Moreover, the tumors that arise in arsenic-exposed individuals also exhibit
      signs of EGFR pathway dysregulation. Further work is needed to assess the
      clinical utility of targeting the EGFR pathway in subgroups of lung cancer
      patients who have been exposed to elevated levels of arsenic.

PMID- 19168571
TI  - The use of nasal dosimetry models in the risk assessment of inhaled gases.

PMID- 19168572
TI  - Embryonic stem cell test remastered: comparison between the validated EST and the
      new molecular FACS-EST for assessing developmental toxicity in vitro.
AB  - The embryonic stem cell test (EST) represents a reliable, scientifically
      validated in vitro system for the detection and classification of compounds
      according to their teratogenic potency. However, some serious issues were
      frequently raised against the widespread implementation and practicability of the
      EST in its original version. Most importantly, the evaluation of the
      morphological endpoint of beating cell agglomerates requires extensive
      experimental experience and is prone to misjudgment. Also, the testing period of
      10 days is too long and costly to be attractive for industries interested in high
      throughput screening of potential drug candidates. These drawbacks prompted us to
      work out a new molecular approach based on analysis of the expression of certain
      marker proteins specific for developing heart tissue. We have previously reported
      that quantitative flow cytometry of marker proteins (i.e., sarcomeric myosin
      heavy chain and alpha-actinin) can be performed at day 7 in embryonic stem cells
      from mice and combined with concurrent cell viability analysis. In the present
      study, extensive investigations were performed in order to explore the predictive
      power and validity of the newly established EST, subsequently referred to as
      molecular fluorescence activated cell sorting (FACS)-EST, by applying and
      comparing a set of 10 well-known embryotoxicants that encompasses the full range
      of chemical inherent embryotoxic potencies possible. While the molecular FACS-EST
      offered the same sensitivity compared to the validated EST protocol, the test
      duration could be significantly reduced. Due to significant improvements, this
      new molecular method holds promise as a sensitive, more rapid and reproducible
      screen highly suited to predict developmental toxicity in vivo from in vitro
      data.

PMID- 19168573
TI  - Do intervention fidelity and dose influence outcomes? Results from the move to
      improve worksite physical activity program.
AB  - The purpose of this paper is to evaluate the implementation of the Move to
      Improve worksite physical activity program using a four step framework that
      includes the following: (i) defining the active ingredients, (ii) using good
      methods to measure implementation, (iii) monitoring implementation and (iv)
      relating implementation to outcomes. The intervention active ingredients
      consisted of a goal setting behavior change program, a team competition and
      environmental supports. Intervention fidelity and dose were measured by surveys
      administered to site co-ordinators, team captains and employees. Implementation
      was monitored by the use of biweekly assessments that tracked individual physical
      activity levels and through weekly reports of the project director and site co
      ordinators. Latent growth modeling was conducted to determine whether
      intervention outcomes were affected by site implementation (i.e. fidelity) and/or
      participation by employees (i.e. dose). Results showed high levels of
      intervention fidelity, moderate to high levels of intervention dose delivered and
      moderate levels of the intervention dose received. Level of implementation
      affected the degree of change in vigorous physical activity (Mean = 5.4 versus
      2.2; chi(2) = 4.9, df = 1), otherwise outcome measures were unaffected by
      fidelity and dose. These findings suggest that practitioners should focus more
      energy assuring that the core components are fully implemented and be less
      concerned about the level of participation.

PMID- 19168574
TI  - Targeted inactivation of endothelial lipase attenuates lung allergic inflammation
      through raising plasma HDL level and inhibiting eosinophil infiltration.
AB  - Endothelial lipase (EL) is a novel phospholipase that determines plasma high
      density lipoprotein cholesterol (HDL-C) levels. We have investigated the role of
      HDL-C in lung allergic inflammation by using EL knockout (EL-KO) mice that are
      high in HDL-C. EL-KO and wild-type control mice were sensitized and challenged
      with ovalbumin to evoke eosinophilic inflammation in the lung. EL was expressed
      in epithelial cells, alveolar type II cells, and endothelial cells in the lung,
      and its expression was upregulated during inflammation. Concomitant with
      attenuated hyperresponsiveness of the airway smooth muscles, the number of
      eosinophils in bronchoalveolar lavage and the expression of VCAM-1 were lower in
      EL-KO mice than in control mice. HDL reduced cytokine-induced VCAM-1 expression
      in cultured endothelial cells. When plasma HDL levels were decreased to similar
      levels in both mouse groups by adenovirus-mediated overexpression of EL, however,
      eosinophil infiltration was still lower in EL-KO mice. In vitro adhesion assays
      revealed that EL expression on the cell surface promoted the interaction of
      eosinophils through the ligand-binding function of EL. In summary, targeted
      inactivation of EL attenuated allergic inflammation in the lung, and the
      protective effects in EL-KO mice were associated with high plasma HDL levels,
      downregulation of VCAM-1, and loss of the direct ligand-binding function of EL.
      Thus EL is a novel modulator of the progression of allergic asthma.

PMID- 19168576
TI  - Curcumin attenuates elastase- and cigarette smoke-induced pulmonary emphysema in
      mice.
AB  - Curcumin, a yellow pigment obtained from turmeric (Curcumina longa), is a dietary
      polyphenol that has been reported to possess anti-inflammatory and antioxidant
      properties. The effect of curcumin against the development of pulmonary emphysema
      in animal models is unknown. The aim of this study was to determine whether
      curcumin is able to attenuate the development of pulmonary emphysema in mice.
      Nine-week-old male C57BL/6J mice were treated with intratracheal porcine
      pancreatic elastase (PPE) or exposed to mainstream cigarette smoke (CS) (60
      min/day for 10 consecutive days or 5 days/wk for 12 wk) to induce pulmonary
      inflammation and emphysema. Curcumin (100 mg/kg) or vehicle was administrated
      daily by oral gavage 1 h and 24 h before intratracheal PPE treatment and daily
      thereafter throughout a 21-day period in PPE-exposed mice and 1 h before each CS
      exposure in CS-exposed mice. As a result, curcumin treatment significantly
      inhibited PPE-induced increase of neutrophils in bronchoalveolar lavage fluid at
      6 h and on day 1 after PPE administration, with an increase in antioxidant gene
      expression at 6 h and significantly attenuated PPE-induced air space enlargement
      on day 21. It was also found that curcumin treatment significantly inhibited CS
      induced increase of neutrophils and macrophages in bronchoalveolar lavage fluid
      after 10 consecutive days of CS exposure and significantly attenuated CS-induced
      air space enlargement after 12 wk of CS exposure. In conclusion, oral curcumin
      administration attenuated PPE- and CS-induced pulmonary inflammation and
      emphysema in mice.

PMID- 19168575
TI  - Participation of mitochondrial respiratory complex III in neutrophil activation
      and lung injury.
AB  - Reactive oxygen species (ROS) produced during mitochondrial activity participate
      in the regulation of intracellular signaling pathways. However, there is only
      limited information concerning the role that ROS derived from the mitochondrial
      respiratory chain play in modulating neutrophil activity and participation in
      acute inflammatory processes. Because mitochondrial complex III is a major site
      of ROS formation, we examined whether selective complex III inhibition, through
      exposure of neutrophils to myxothiazol or antimycin A, would affect LPS-induced
      activation. Culture of neutrophils with antimycin A or myxothiazol resulted in
      increased intracellular levels of ROS, including superoxide and hydrogen peroxide
      (H(2)O(2)). Inhibition of complex III activity reduced LPS-induced degradation of
      IkappaB-alpha, nuclear accumulation of NF-kappaB, and proinflammatory cytokine
      production. The effects of antimycin A or myxothiazol appeared to be dependent on
      generation of H(2)O(2) since addition of pegylated catalase to neutrophils
      restored LPS-mediated IkappaB-alpha degradation and production of proinflammatory
      cytokines. Administration of myxothiazol to mice resulted in diminished
      mitochondrial complex III activity in the lungs and decreased severity of LPS
      induced lung injury. These results indicate that inhibition of mitochondrial
      complex III diminishes Toll-like receptor 4-induced neutrophil activation through
      a mechanism dependent on H(2)O(2) generation and also reduces the severity of
      lung injury due to LPS exposure, a pathophysiologic process in which neutrophils
      play a major role.

PMID- 19168577
TI  - Differential regulation of sphingosine kinases 1 and 2 in lung injury.
AB  - Two mammalian sphingosine kinase (SphK) isoforms, SphK1 and SphK2, possess
      identical kinase domains but have distinct kinetic properties and subcellular
      localizations, suggesting each has one or more specific roles in sphingosine-1
      phosphate (S1P) generation. Although both kinases use sphingosine as a substrate
      to generate S1P, the mechanisms controlling SphK activation and subsequent S1P
      generation during lung injury are not fully understood. In this study, we
      established a murine lung injury model to investigate LPS-induced lung injury in
      SphK1 knockout (SphK1(-/-)) and wild-type (WT) mice. We found that SphK1(-/-)
      mice were much more susceptible to LPS-induced lung injury compared with their WT
      counterparts, quantified by multiple parameters including cytokine induction.
      Intriguingly, overexpression of WT SphK1 delivered by adenoviral vector to the
      lungs protected SphK1(-/-) mice from lung injury and attenuated the severity of
      the response to LPS. However, adenoviral overexpression of a SphK1 kinase-dead
      mutant (SphKKD) in SphK1(-/-) mouse lungs further exacerbated the response to LPS
      as well as the extent of lung injury. WT SphK2 adenoviral overexpression also
      failed to provide protection and, in fact, augmented the degree of LPS-induced
      lung injury. This suggested that, in vascular injury, S1P generated by SphK2
      activation plays a distinctly separate role compared with SphK1-dependent S1P
      generation and survival signaling. Microarray and real-time RT-PCR analysis of
      SphK1 and SphK2 expression levels during lung injury revealed that, in WT mice,
      LPS treatment caused significantly enhanced SphK1 expression ( approximately 5x)
      levels within 6 h, which declined back to baseline levels by 24 h posttreatment.
      In contrast, expression of SphK2 was gradually induced following LPS treatment
      and was elevated within 24 h. Collectively, our results for the first time
      demonstrate distinct functional roles of the two SphK isoforms in the regulation
      of LPS-induced lung injury.

PMID- 19168578
TI  - Microparticles harboring Sonic Hedgehog promote angiogenesis through the
      upregulation of adhesion proteins and proangiogenic factors.
AB  - Microparticles (MPs) are small fragments generated from the plasma membrane after
      cell stimulation or apoptosis. We have recently shown that MPs harboring the
      morphogen Sonic Hedgehog (MPs(Shh+)) correct endothelial injury by release of
      nitric oxide from endothelial cells [Agouni, Mostefai, Porro, Carusio, Favre,
      Richard, Henrion, Martinez and Andriantsitohaina (2007) FASEB J., 21, 2735-2741].
      Here, we show that MPs(Shh+) induce the formation of capillary-like structures in
      an in vitro model using human endothelial cells, although they inhibited cell
      migration. Besides, MPs(Shh+) regulate cell proliferation. Both cell adhesion and
      expression of proteins involved in this process such as Rho A and phosphorylation
      of focal-activated kinase were increased by MPs(Shh+), via a Rho-associated
      coiled-coil-containing protein kinase inhibitor-sensitive pathway. We demonstrate
      that MPs(Shh+) increase messenger RNA and protein levels of proangiogenic factors
      as measured by quantitative reverse transcription-polymerase chain reaction and
      western blot. In spite of vascular endothelial growth factor expression,
      conditioned media from endothelial cells treated avec MPs(Shh+) reduces
      angiogenesis. Interestingly, the effects induced by MPs(Shh+) on the formation of
      capillary-like structures, expression of adhesion molecules and proangiogenic
      factors were reversed after silencing of the Shh receptor, using small
      interfering RNA or when Sonic Hedgehog (Shh) signaling was pharmacologically
      inhibited with cyclopamine. Taken together, we show that Shh carried by MPs(Shh+)
      regulate angiogenesis probably through both a direct and an indirect mechanisms,
      and we propose that MPs harboring Shh may contribute to the generation of a
      vascular network in pathologies associated with tumor growth.

PMID- 19168579
TI  - Complex relationship between TCTP, microtubules and actin microfilaments
      regulates cell shape in normal and cancer cells.
AB  - Translationally controlled tumor-associated protein (TCTP) is a ubiquitous and
      highly conserved protein implicated in cancers. Here, we demonstrate that
      interactions of TCTP with microtubules (MTs) are functionally important but
      indirect, and we reveal novel interaction of TCTP with the actin cytoskeleton.
      Firstly, immunofluorescence in Xenopus XL2 cells revealed cytoplasmic fibers
      stained with TCTP but not with tubulin antibodies, as well as MTs free of TCTP.
      Furthermore, TCTP localized to a subset of actin-rich fibers in migrating cells.
      Secondly, Xenopus laevis TCTP did not affect in vitro assembly/disassembly of MTs
      and lacked MT-binding affinity both in pull-down assays and in cell-free
      extracts. Although TCTP also failed to bind to purified filamentous actin (F
      actin), it was associated with microfilaments in cell-free extracts. Thirdly,
      TCTP concentrated in mitotic spindle did not colocalize with MTs and was easily
      dissociated from these structures except at the poles. Finally, RNA interference
      knockdown of TCTP in XL2 and HeLa cells provoked drastic, MT-dependent shape
      change. These data show that although TCTP interacts with MTs, it does not behave
      as classic MT-associated protein. Our evidence for an association of TCTP with F
      actin structures, and for an involvement in cell shape regulation, implicates
      this protein in integrating cytoskeletal interactions both in interphase and
      mitosis providing a new avenue to fully understand the role of TCTP.

PMID- 19168581
TI  - FAS promoter polymorphisms and cancer risk: a meta-analysis based on 34 case
      control studies.
AB  - FAS is a cell surface receptor involved in apoptotic signal transmission and
      plays important roles in the etiology of cancer. The -1377G>A and -670A>G
      polymorphisms of the FAS gene influence the FAS transcription and have been
      implicated in cancer risk. However, the results from the published studies on the
      association between these two FAS polymorphisms and cancer risk are conflicting.
      To derive a more precise estimation of association between the FAS polymorphisms
      and risk of cancer, we performed a meta-analysis of 11 461 cancer cases and 12
      708 controls from 34 published case-control studies for these two polymorphisms.
      We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the
      strength of the association. Overall, individuals with the -1377AA genotype were
      associated with higher cancer risk than those with the -1377GG (OR = 1.21, 95%
      CI: 1.08-1.36, P(heterogeneity) = 0.062) or GA/GG (OR = 1.23, 95% CI: 1.10-1.36,
      P(heterogeneity) = 0.060) genotypes, whereas the -670GG genotype had no effects
      on overall cancer risk. In the stratified analyses for the -1377G>A polymorphism,
      there was a significantly increased risk of breast cancer but a significantly
      decreased risk of melanoma in a dominant model. Moreover, a significantly
      increased risk was observed among smokers in a recessive model (OR = 1.96, 95%
      CI: 1.55-2.49; P(heterogeneity) = 0.528). Although some modest bias could not be
      eliminated, this meta-analysis suggested that the FAS -1377A allele is a low
      penetrant risk factor for cancer development, particularly among smokers.

PMID- 19168580
TI  - The prolyl isomerase Pin1 interacts with a ribosomal protein S6 kinase to enhance
      insulin-induced AP-1 activity and cellular transformation.
AB  - Phosphorylation of proteins on serine or threonine residues that immediately
      precede proline (pSer/Thr-Pro) is specifically catalyzed by the peptidyl-prolyl
      cis-trans isomerase Pin1 and is a central signaling mechanism in cell
      proliferation and transformation. Although Pin1 is frequently overexpressed in
      hepatocellular carcinoma (HCC), the molecular mechanism of Pin1 in HCC has not
      been completely elucidated. Here, we show that Pin1 interacts with p70S6K in
      vitro and ex vivo. Overexpression of Pin1 resulted in enhanced p70S6K
      phosphorylation induced by insulin in SK-HEP-1 cells. In contrast, Pin1(-/-)
      mouse embryonic fibroblasts (MEFs) exhibited significantly decreased insulin
      induced p70S6K phosphorylation compared with Pin1(+/+) MEFs. Furthermore, Pin1
      enhanced the insulin-induced extracellular signal-regulated protein kinase
      (ERK)1/2 phosphorylation through its interaction with p70S6K, whereas the
      inhibition of p70S6K activity by rapamycin suppressed insulin-induced ERK1/2
      phosphorylation in SK-HEP-1 cells. Hence, Pin1 affected activator protein-1
      activity through p70S6K-ERK1/2 signaling in SK-HEP-1 cells. Most importantly,
      Pin1-overexpressing JB6 Cl41 cells enhanced neoplastic cell transformation
      promoted by insulin much more than green fluorescent protein-overexpressing JB6
      Cl41 control cells. These results imply that Pin1 amplifies insulin signaling in
      hepatocarcinoma cells through its interaction with p70S6K, suggesting that Pin1
      plays an important role in insulin-induced tumorigenesis and is a potential
      therapeutic target in hepatocarcinoma.

PMID- 19168582
TI  - Re: Modulation of basal and squamous cell carcinoma by endogenous estrogen in
      mouse models of skin cancer.

PMID- 19168583
TI  - Nitric oxide synthase gene polymorphisms and prostate cancer risk.
AB  - Nitric oxide (NO) induces cytotoxicity and angiogenesis, and may play a role in
      prostate carcinogenesis, potentially modulated by environmental exposures. We
      evaluated the association of prostate cancer with genetic polymorphisms in two
      genes related to intracellular NO: NOS2A [inducible nitric oxide synthase (NOS); 
      2892T>C, Ex16 + 14C>T (S608L), IVS16 + 88T>G and IVS20 + 524G>A] and NOS3
      [endothelial NOS; IVS1-762C>T, Ex7-43C>T (D258D), IVS7-26A>G, Ex8-63G>T (E298D)
      and IVS15-62G>T]. Prostate cancer cases (n = 1320) from the screening arm of the
      Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were frequency
      matched to controls (n = 1842), by age, race, time since initial screening and
      year of blood draw. An antioxidant score [range 3-12; low (3-7) versus high (8
      12)] was created by summing the quartile levels of vitamin E, beta-carotene and
      lycopene, which were coded from 1 to 4, respectively. The global tests for all
      eight single-nucleotide polymorphisms (SNPs) (excluding NOS2A-2892T>C, with low
      minor allele frequency) were statistically significant for prostate cancer (P =
      0.005), especially for aggressive cancer (stage III-IV or Gleason score > or = 7)
      (P = 0.01). The NOS2A IVS16 + 88 GT/TT was associated with increased prostate
      cancer risk (odds ratio = 1.24, 95% confidence interval = 1.00-1.54), whereas the
      IVS20 + 524 AG/GG was associated with decreased risk (0.77, 0.66-0.90). The NOS3
      IVS7-26GG was associated with increased prostate cancer risk (1.33, 1.07-1.64).
      All these SNPs showed significant associations with aggressive cancer and not for
      non-aggressive cancer. In the evaluation of effect modification, the effect of
      the NOS2A IVS16 + 88 GT/TT on aggressive cancer was stronger among subjects with
      higher antioxidant intake (1.61, 1.18-2.19; P(interaction) = 0.01). Our results
      suggest that NOS gene polymorphisms are genetic susceptibility factors for
      aggressive prostate cancer.

PMID- 19168584
TI  - Association between frequent CpG island methylation and HER2 amplification in
      human breast cancers.
AB  - The presence of frequent methylation of CpG islands (CGIs), designated as the CpG
      island methylator phenotype in some cancers, is associated with distinct
      clinicopathological characteristics, including gene amplification, in individual
      tumor types. Amplification of HER2 in human breast cancers is an important
      prognostic and therapeutic target, but an association between HER2 amplification
      and frequent CGI methylation is unknown. To clarify the association, we here
      quantified methylation levels of promoter CGIs of 11 genes, which are unlikely to
      confer growth advantage to cells, in 63 human breast cancers. The number of
      methylated genes in a cancer did not obey a bimodal distribution, and the 63
      cancers were classified into those with frequent methylation (n = 16), moderate
      methylation (n = 26) and no methylation (n = 21). The incidence of HER2
      amplification was significantly higher in the cancers with frequent methylation
      (11 of 16) than in those with no methylation (2 of 21, P = 0.001). Also, the
      number of methylated genes correlated with the degree of HER2 amplification (r =
      0.411, P = 0.002). Correlation analysis with clinicopathological characteristics
      and methylation of CDKN2A, BRCA1 and CDH1 revealed that frequent methylation had
      significant correlation with higher nuclear grades (P = 0.001). These showed that
      frequent methylation had a strong association with HER2 amplification in breast
      cancers and suggested that frequent methylation can be a determinant of various
      characteristics in a fraction of human breast cancers.

PMID- 19168585
TI  - Leptin enhances cell migration in human chondrosarcoma cells through OBRl leptin
      receptor.
AB  - Leptin, an adipocyte-derived cytokine that is closely associated with obesity,
      has recently been shown to be involved in carcinogenesis and cancer progression.
      Integrins are the major adhesive molecules in mammalian cells and have been
      associated with metastasis of cancer cells. In this study, we found that leptin
      increased the migration and the expression of alphavbeta3 integrin in human
      chondrosarcoma cells. We also found that human chondrosarcoma tissues and
      chondrosarcoma cell lines had significant expression of the long form (OBRl)
      leptin receptor, which was higher than that in normal cartilage and human primary
      chondrocyte. Leptin-mediated migration and integrin upregulation were attenuated
      by OBRl receptor antisense oligonucleotide. Activations of insulin receptor
      substrate (IRS)-1, phosphatidylinositol 3-kinase (PI3K), Akt and nuclear factor
      kappaB (NF-kappaB) pathways after leptin treatment were demonstrated, and leptin
      induced expression of integrin and migration activity was inhibited by the
      specific inhibitor, small-interfering RNA and mutant of IRS-1, PI3K, Akt and NF
      kappaB cascades. Taken together, our results indicated that leptin enhances the
      migration of chondrosarcoma cells by increasing alphavbeta3 integrin expression
      through the OBR1/IRS-1/PI3K/Akt/NF-kappaB signal transduction pathway.

PMID- 19168587
TI  - The role of estrogens in melanoma and skin cancer.

PMID- 19168586
TI  - The oxysterol receptor LXR inhibits proliferation of human breast cancer cells.
AB  - The oxysterol receptors [liver X receptors (LXRalpha and LXRbeta)] regulate
      cholesterol and lipid biosynthesis and several studies link dysregulation of
      these metabolic pathways to aberrant cell growth. Here, we show that activation
      of LXR significantly reduced proliferation in several human breast cancer cells
      lines. LXR suppressed messenger RNA and/or protein expression of Skp2, cyclin A2,
      cyclin D1 and estrogen receptor (ER) alpha, whereas it increased the expression
      of p53 at the protein level and maintained the retinoblastoma protein in a
      hypophosphorylated active form. These changes may constitute part of the
      molecular mechanisms behind the antiproliferative effect of LXR. Furthermore,
      activation of LXR induced expression of key lipogenic genes including sterol
      regulatory element-binding protein 1c (SREBP1c), fatty acid synthase and stearoyl
      coenzyme A desaturase 1, leading to increased triglyceride production in MCF7
      cells. Small interfering RNA knockdown of SREBP1c, a master regulator of the
      lipid biosynthesis, did not abolish the antiproliferative effect of LXR in these
      cells. Combined these studies identify LXRs as both antiproliferative and
      lipogenic factors in breast cancer cells and indicate that the antiproliferative
      effect of LXRs is independent of lipid biosynthesis.

PMID- 19168588
TI  - Dietary variables associated with DNA N7-methylguanine levels and O6-alkylguanine
      DNA-alkyltransferase activity in human colorectal mucosa.
AB  - Components of human diets may influence the incidence of colorectal adenomas, by
      modifying exposure or susceptibility to DNA-damaging alkylating agents. To
      examine this hypothesis, a food frequency questionnaire was used to assess the
      diet of patients recruited for a case-referent study where biopsies of normal
      colorectal mucosa were collected during colonoscopy and subsequently analysed for
      DNA N7-methylguanine (N7-MeG) levels, as an indicator of exposure, and activity
      of the DNA repair protein O6-alkylguanine DNA-alkyltransferase (MGMT), as an
      indicator of potential susceptibility. Cases with histologically proven
      colorectal adenomas (n = 38) were compared with referents (n = 35) free of
      gastrointestinal neoplasia. The case group consumed significantly more red meat
      (4.5 versus 3.4 servings/week, P < 0.05), processed meats, (4.7 versus 3.2
      servings/week, P < 0.05) and % food energy as fat (34.9 versus 30.7%, P < 0.001).
      N7-MeG [mean: 95% confidence interval (CI)] levels were significantly lower in
      the group that consumed the highest proportion of dietary fibre/1000 kcal in
      comparison with the group with the lowest intake (0.61; 0.35-0.86 versus 1.88;
      0.88-2.64 micromol/mol dG, P < 0.05). N7-MeG levels were also inversely
      associated with folate consumption (P < 0.05). MGMT activity (mean; 95% CI) was
      significantly higher in the group with the lowest consumption of vegetables than
      in the group with the greatest vegetable consumption (7.02; 5.70-8.33 versus
      4.93; 3.95-5.91 fmol/microg DNA, P < 0.05). Our results are consistent with the
      hypothesis that dietary factors may modify exposure or susceptibility,
      respectively, to DNA damage by alkylating agents.

PMID- 19168593
TI  - IL-21 ensures TGF-beta 1-induced IgA isotype expression in mouse Peyer's patches.
AB  - It is well established that TGF-beta1 induces IgA and IgG2b class-switching
      recombination in murine B cells. In the present study, we assessed the activity
      of IL-21 along with TGF-beta1 in Ig synthesis by murine spleen B cells. IL-21
      showed antiproliferative activity on LPS-activated splenic B cells, comparable
      with that of TGF-beta1. IL-21 alone had little effect on IgA secretion and
      decreased other isotypes. Likewise, IL-21 also did not alter the TGF-beta1
      induced IgA synthesis and concurrently diminished the syntheses of IgM and IgG2a,
      which were repressed by TGF-beta1. Unexpectedly, IL-21 inhibited the TGF-beta1
      induced IgG2b production. This IL-21 effect was examined using B cells from IL
      21R knockout mice, where the IgA production profile was paralleled by that seen
      in wild-type B cells. However, the inhibitory effect of IL-21 on TGF-beta1
      induced IgG2b synthesis was not seen in the IL-21R(-/-) mouse, suggesting that IL
      21 causes TGF-beta1-stimulated B cells to decrease IgG2b synthesis. Expression
      patterns of Ig germ-line alpha(GL alpha)/GL gamma 2b transcripts under the
      influence of TGF-beta1 and IL-21 were paralleled by IgA/IgG2b secretion. This was
      also observed in the activities of GL(alpha) and GL(gamma 2b) promoters. These
      results indicate that IL-21 decreases IgG2b secretion mainly through inhibition
      of GL(gamma 2b) transcription and is ultimately associated with selective IgA
      secretion induced by TGF-beta1. Our results showed that IL-21 was expressed in
      greater magnitude in Peyer's patches (PP) than in spleen. These results suggest
      that IL-21 has an important effect on selective IgA(+) B cell commitment in PP.

PMID- 19168589
TI  - Variants in hormone-related genes and the risk of biliary tract cancers and
      stones: a population-based study in China.
AB  - Biliary tract cancers, encompassing gallbladder, extrahepatic bile duct and
      ampulla of Vater cancers, are uncommon but often fatal malignancies. Hormone
      related factors, including parity, oral contraceptive use, obesity, and
      gallstones, have been implicated in the etiology of these cancers. To further
      clarify the role of hormones in biliary tract cancers and biliary stones, we
      genotyped 18 single-nucleotide polymorphisms (SNPs) in nine genes involved in
      steroid hormone biosynthesis, metabolism and transport in a population-based case
      control study in Shanghai, China. This study included subjects who completed an
      interview and provided blood, which totaled 411 biliary tract cancer and 893
      biliary stone patients and 786 healthy Shanghai residents. The CYP1A1 IVS1 + 606
      (rs2606345) T allele was associated with gallbladder [odds ratio (OR) = 2.0, 95%
      confidence interval (CI), 1.3-3.0] and bile duct cancers (OR = 1.8, 95% CI = 1.1
      3.1), whereas the CYP1A1 Ex7 + 131 (rs1048943) G allele was associated with
      ampulla of Vater cancer (OR = 2.9, 95% CI = 1.5-5.4). After taking into account
      multiple comparisons for SNPs within each gene, CYP1A1 was significantly
      associated with gallbladder (P = 0.004) and ampulla of Vater cancers (P = 0.01),
      but borderline with bile duct cancer (P = 0.06). The effect of CYP1A1 IVS1 + 606
      on gallbladder cancer was more pronounced among non-obese (body mass index < 23)
      (OR = 3.3, 95% CI = 1.8-6.1; P interaction = 0.001). Among women taking oral
      contraceptives, the effect of SHBG Ex8 + 6 (rs6259) on gallbladder cancer (OR =
      6.7, 95% CI = 2.2-20.5; P interaction = 0.001) and stones (OR = 2.3, 95% CI = 1.1
      4.9; P-interaction = 0.05) was statistically significant. Our findings suggest
      that common variants in hormone-related genes contribute to the risk of biliary
      tract cancers and stones, possibly by modulating hormone metabolism.

PMID- 19168594
TI  - Behavioral response of human spermatozoa to a concentration jump of
      chemoattractants or intracellular cyclic nucleotides.
AB  - BACKGROUND: A major question in mammalian sperm chemotaxis is whether the cells
      sense a chemoattractant gradient by comparing the chemoattractant concentration
      between time points or between spatial points. METHODS: To resolve this question,
      we exposed human spermatozoa to a temporal chemoattractant gradient under
      conditions of no spatial gradient by rapidly mixing the cells with progesterone
      or bourgeonal on a microscope slide and analyzing their swimming with motion
      analysis software. RESULTS: The cells responded within seconds with an increase
      in velocity and lateral head displacement, and with a decrease in the linearity
      of swimming, becoming hyperactivated at the peak of the response. All the
      responses were transient, lasting for a number of seconds. Essentially similar
      results were obtained upon intracellular photorelease of cyclic adenosine
      monophosphate or cyclic guanosine monophosphate, which are thought to be involved
      in mediating the chemotactic response. CONCLUSION: These results suggest that
      human spermatozoa sense and respond to a temporal chemoattractant gradient. On
      the basis of these observations, we propose a potential model for the chemotactic
      response of spermatozoa in a spatial chemoattractant gradient.

PMID- 19168595
TI  - Common variants of hepatocyte nuclear factor 1beta are associated with type 2
      diabetes in a Chinese population.
AB  - OBJECTIVE: Hepatocyte nuclear factor 1beta (HNF1beta) is a transcription factor
      that is critical for pancreatic cell formation and glucose homeostasis. Previous
      studies have reported that common variants of HNF1beta were associated with type
      2 diabetes in Caucasians and West Africans. However, analysis in the subjects
      from the Botnia study and Malmo Preventive Project produced conflicting results,
      and the role for HNF1beta in type 2 diabetes susceptibility remains unclear. We
      therefore investigated common variants across the HNF1beta gene in a Chinese
      population. RESEARCH DESIGN AND METHODS: Fifteen tagging single nucleotide
      polymorphisms (SNPs) were analyzed for association with type 2 diabetes in
      subjects with type 2 diabetes (n = 1,859) and normal glucose regulation (n =
      1,785). RESULTS: Consistent with the initial study, we observed evidence that the
      risk G allele of rs4430796 in intron 2 was significantly associated with type 2
      diabetes (odds ratio 1.16 [95% CI 1.05-1.29], P = 0.0035, empirical P = 0.0475).
      Furthermore, the at-risk G allele was associated with earlier age at diagnosis in
      the type 2 diabetic subjects (P = 0.0228). CONCLUSIONS: The result of this study
      provides evidence that variants in the HNF1beta region contribute to
      susceptibility to type 2 diabetes in the Chinese population.

PMID- 19168596
TI  - TCF7L2 regulates late events in insulin secretion from pancreatic islet beta
      cells.
AB  - OBJECTIVE: Polymorphisms in the human TCF7L2 gene are associated with reduced
      insulin secretion and an increased risk of type 2 diabetes. However, the
      mechanisms by which TCF7L2 affect insulin secretion are still unclear. We define
      the effects of TCF7L2 expression level on mature beta-cell function and suggest a
      potential mechanism for its actions. RESEARCH DESIGN AND METHODS: TCF7L2
      expression in rodent islets and beta-cell lines was altered using RNAi or
      adenoviral transduction. Beta-cell gene profiles were measured by quantitative
      real-time PCR and the effects on intracellular signaling and exocytosis by live
      cell imaging, electron microscopy, and patch clamp electrophysiology. RESULTS:
      Reducing TCF7L2 expression levels by RNAi decreased glucose- but not KCl-induced
      insulin secretion. The glucose-induced increments in both ATP/ADP ratio and
      cytosolic free Ca2+ concentration ([Ca2+]i) were increased compared with
      controls. Overexpression of TCF7L2 exerted minor inhibitory effects on glucose
      regulated changes in [Ca2+]i and insulin release. Gene expression profiling in
      TCF7L2-silenced cells revealed increased levels of mRNA encoding syntaxin 1A but
      decreased Munc18-1 and ZnT8 mRNA. Whereas the number of morphologically docked
      vesicles was unchanged by TCF7L2 suppression, secretory granule movement
      increased and capacitance changes decreased, indicative of defective vesicle
      fusion. CONCLUSION: TCF7L2 is involved in maintaining expression of beta-cell
      genes regulating secretory granule fusion. Defective insulin exocytosis may thus
      underlie increased diabetes incidence in carriers of the at-risk TCF7L2 alleles.

PMID- 19168597
TI  - BMI changes during childhood and adolescence as predictors of amount of adult
      subcutaneous and visceral adipose tissue in men: the GOOD Study.
AB  - OBJECTIVE: The amount of visceral adipose tissue is a risk factor for the
      metabolic syndrome. It is unclear how BMI changes during childhood and
      adolescence predict adult fat distribution. We hypothesized that there are
      critical periods during development for the prediction of adult subcutaneous and
      visceral fat mass by BMI changes during childhood and adolescence. RESEARCH
      DESIGN AND METHODS: Detailed growth charts were retrieved for the men
      participating in the population-based Gothenburg Osteoporosis and Obesity
      Determinants (GOOD) Study (n = 612). Body composition was analyzed using dual
      energy X-ray absorptiometry and adipose tissue areas using abdominal computed
      tomography at 18 to 20 years of age. RESULTS: The main finding in the present
      study was that subjects with increases in BMI Z score of more than 1 SD during
      adolescence had, independent of prepubertal BMI, both larger subcutaneous (+138%;
      P < 0.001) and visceral adipose tissue areas (+91%; P < 0.001) than subjects with
      unchanged BMI Z-score. In contrast, subjects with increases in BMI Z score of
      more than 1 SD during late childhood had a larger amount of adult subcutaneous
      adipose tissue (+83%; P < 0.001) than subjects with unchanged BMI Z score but an
      unaffected amount of visceral adipose tissue. BMI changes during adolescence
      predict both visceral and subcutaneous adipose tissue of the abdomen, whereas BMI
      changes during late childhood predict only the subcutaneous adipose tissue.
      CONCLUSIONS: The amount of visceral adipose tissue in young adult men was
      associated with BMI changes specifically during adolescence, whereas the amount
      of subcutaneous adipose tissue was associated with BMI changes during both late
      childhood and adolescence.

PMID- 19168598
TI  - FOXO1 plays an important role in enhanced microvascular cell apoptosis and
      microvascular cell loss in type 1 and type 2 diabetic rats.
AB  - OBJECTIVE: To investigate early events leading to microvascular cell loss in
      diabetic retinopathy. RESEARCH DESIGN AND METHODS: FOXO1 was tested in vivo by
      DNA binding activity and by nuclear translocation in microvascular cells in
      retinal trypsin digests. In vivo studies were undertaken in STZ-induced diabetic
      rats and Zucker diabetic fatty rats using the tumor necrosis factor (TNF)
      specific blocker, pegsunercept, or by inhibiting FOXO1 with RNAi. Microvascular
      cell apoptosis, formation of pericyte ghosts, and acellular capillaries were
      measured. Upstream and downstream effects of high-glucose-induced FOXO1 were
      tested on rat microvascular endothelial cells (RMECs) by small-interfering RNA
      (siRNA) in vitro. RESULTS: DNA binding or nuclear translocation of FOXO1, which
      was reduced by TNF inhibition, was elevated in type 1 and type 2 diabetic
      retinas. Diabetes stimulated microvascular cell apoptosis; pericyte ghost and
      acellular capillary development was inhibited by FOXO1 siRNA. High glucose in
      vitro decreased FOXO1 phosphorylation and DNA binding activity and decreased Akt
      phosphorylation in RMECs. High-glucose-stimulated FOXO1 DNA binding activity was
      mediated through TNF-alpha and formation of reactive oxygen species (ROS), while
      inhibitors of TNF and ROS and FOXO1 siRNA reduced high-glucose-enhanced RMEC
      apoptosis. The caspase-3/7 activity and capacity of high glucose to increase mRNA
      levels of several genes that regulate RMEC activation and apoptosis were knocked
      down by FOXO1 siRNA. CONCLUSIONS: FOXO1 plays an important role in rat retinal
      microvascular cell loss in type 1 and type 2 diabetic rats and can be linked to
      the effect of high glucose on FOXO1 activation.

PMID- 19168600
TI  - Inadequacies of glucocorticoid replacement and improvements by physiological
      circadian therapy.
AB  - Patients with adrenal insufficiency need lifelong glucocorticoid replacement, but
      many suffer from poor quality of life, and overall there is increased mortality.
      Moreover, it appears that use of glucocorticoids at the higher end of the
      replacement dose range is associated with increased risk for cardiovascular and
      metabolic bone disease. These data highlight some of the inadequacies of current
      regimes. The cortisol production rate is estimated to be equivalent to 5.7-7.4
      mg/m(2) per day, and a major difficulty for replacement regimes is the inability
      to match the distinct circadian rhythm of circulating cortisol levels, which are
      low at the time of sleep onset, rise between 0200 and 0400 h, peaking just after
      waking and then fall during the day. Another issue is that current dose
      equivalents of glucocorticoids used for replacement are based on anti
      inflammatory potency, and few data exist as to doses needed for equivalent
      cardiovascular and bone effects. Weight-adjusted, thrice-daily dosing using
      hydrocortisone (HC) reduces glucocorticoid overexposure and represents the most
      refined regime for current oral therapy, but does not replicate the normal
      cortisol rhythm. Recently, proof-of-concept studies have shown that more
      physiological circadian glucocorticoid therapy using HC infusions and newly
      developed oral formulations of HC have the potential for better biochemical
      control in patients with adrenal insufficiency. Whether such physiological
      replacement will have an impact on the complications seen in patients with
      adrenal insufficiency will need to be analysed in future clinical trials.

PMID- 19168599
TI  - Type 1 diabetes in the BB rat: a polygenic disease.
AB  - OBJECTIVE: Two type 1 diabetes susceptibility genes have been identified in the
      spontaneously diabetic biobreeding diabetes-prone (BBDP) rat, the major
      histocompatibility complex (MHC) (RT1) class II u haplotype (Iddm1) and Gimap5
      (Iddm2). The strong effects of these have impeded previous efforts to map
      additional loci. We tested the hypothesis that type 1 diabetes is a polygenic
      disease in the BBDP rat. RESEARCH DESIGN AND METHODS: We performed the most
      comprehensive genome-wide linkage analysis for type 1 diabetes, age of disease
      onset (AOO), and insulitis subphenotypes in 574 F2 animals from a cross
      intercross between BBDP and type 1 diabetes-resistant, double congenic ACI.BBDP
      RT1u,Gimap5 (ACI.BB(1u.lyp)) rats, where both Iddm1 and Iddm2 were fixed as BBDP.
      RESULTS: A total of 19% of these F2 animals developed type 1 diabetes, and eight
      type 1 diabetes susceptibility loci were mapped, six showing significant linkage
      (chromosomes 1, 3, 6 [two loci], 12, and 14) and two (chromosomes 2 and 17)
      suggestive linkage. The chromosomes 6, 12, and 14 intervals were also linked to
      the severity of islet infiltration by immunocytes, while those on chromosomes 1,
      6 (two loci), 14, 17, and a type 1 diabetes-unlinked chromosome 8 interval showed
      significant linkage to the degree of islet atrophy. Four loci exhibited
      suggestive linkage to AOO on chromosomes 2 (two loci), 7, and 18 but were
      unlinked to type 1 diabetes. INS, PTPN22, IL2/IL21, C1QTNF6, and C12orf30,
      associated with human type 1 diabetes, are contained within the chromosomes 1, 2,
      7, and 12 loci. CONCLUSIONS: This study demonstrates that the BBDP diabetic
      syndrome is a complex, polygenic disease that may share additional susceptibility
      genes besides MHC class II with human type 1 diabetes.

PMID- 19168601
TI  - Experiences of partners of people in the early stages of multiple sclerosis.
AB  - BACKGROUND: Partners of people with multiple sclerosis are known to experience a
      heavy physical and psychological burden. However, little research has explored,
      in detail, the partners' experience in the first years after diagnosis. The aim
      of this study was to explore and describe the experiences of partners of people
      who are in the relatively early stages of multiple sclerosis. METHODS: Fifteen
      semi-structured telephone interviews were conducted to assess partners' concerns
      and difficulties. Data were audio-taped, transcribed, and analysed using an
      inductive thematic analysis. RESULTS: Key themes were being unsure of what the
      future might hold and feeling helpless and out of control. Furthermore, partners
      reported that other people could not understand and support them, which led to a
      feeling of social isolation. CONCLUSION: The research illustrates the disruptive
      impact that MS has on partners' lives and highlights the need for support to
      focus on partners' needs even in early stages of the disease.

PMID- 19168602
TI  - The effect of levetiracetam on tremor severity and functionality in patients with
      multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) intention tremor is a disabling symptom,
      which is difficult to treat. OBJECTIVES: To investigate the effects of
      levetiracetam, an antiepileptic drug, on tremor severity and related
      functionality in MS. METHODS: A randomized, double-blind, placebo-controlled,
      cross-over study examined the effects of 6 weeks of oral levetiracetam
      administration (starting dose=250 mg/day, maximal dose=2000 mg/day) in 18 MS
      patients with disabling intention tremor. Primary outcome was Fahn's Tremor
      Rating Scale (FTRS) A&B. Secondary outcome measures were the nine-hole peg test,
      patient's opinion rated with the visual analog scale, FTRS C, and an activities
      of daily life questionnaire and validated tremor indexes derived during the
      performance of a digitized spiral drawing task and a wrist step-tracking task.
      Repeated measures analysis of variance and Friedman tests were applied. RESULTS:
      In all, 14 patients completed the trial. Maximal dose intake ranged from 1000 to
      most commonly 2000 mg, depending on patients' tolerance level. No significant
      effects of levetiracetam were found for any outcome measure. Further analyses on
      subgroups with different tremor severity showed no differential effects. Eight
      patients reported adverse events such as fatigue and stomach ache. CONCLUSIONS:
      Levetiracetam intake of 2000 mg/day did not affect tremor severity or
      functionality in patients with MS.

PMID- 19168604
TI  - Rebuttal: the modern concept of the procaryote.

PMID- 19168605
TI  - Problems with "procaryote".

PMID- 19168606
TI  - The modern concept of the procaryote.

PMID- 19168607
TI  - Mutational analysis and homology-based modeling of the IntDOT core-binding
      domain.
AB  - Tyrosine recombinases mediate a wide range of important genetic rearrangement
      reactions. Models for tyrosine recombinases have been based largely on work done
      on the integrase of phage lambda and recombinases like Cre, Flp, and XerC/D. All
      of these recombinases share a common amino acid signature that is important for
      catalysis. Several conjugative transposons (CTns) encode recombinases that are
      also members of the tyrosine recombinase family, but the reaction that they
      catalyze differs in that recombination does not require homology in the
      attachment sites. In this study, we examine the role of the core-binding (CB)
      domain of the CTnDOT integrase (IntDOT) that is located adjacent to the catalytic
      domain of the protein. Since there is no crystal structure for any of the CTn
      integrases, we began with a predicted three-dimensional structure produced by
      homology-based modeling. Amino acid substitutions were made at positions
      predicted by the model to be close to the DNA. Mutant proteins were tested for
      the ability to mediate integration in vivo and for in vitro DNA-binding,
      cleavage, and ligation activities. We identified for the first time nonconserved
      amino acid residues in the CB domain that are important for catalytic activity.
      Mutant proteins with substitutions at three positions in the CB domain are
      defective for DNA cleavage but still proficient in ligation. The positions of the
      residues in the complex suggest that the mutant residues affect the positioning
      of the cleaved phosphodiester bond in the active site without disruption of the
      ligation step.

PMID- 19168608
TI  - The molecular alarmone (p)ppGpp mediates stress responses, vancomycin tolerance,
      and virulence in Enterococcus faecalis.
AB  - The stringent response is a global bacterial response to stress that is mediated
      by accumulation of the alarmone (p)ppGpp. In this study, treatment with mupirocin
      was shown to induce high levels of (p)ppGpp production in Enterococcus faecalis,
      indicating that this nosocomial pathogen can mount a classic stringent response.
      In addition, (p)ppGpp was found to accumulate in cells subjected to heat shock,
      alkaline shock, and inhibitory concentrations of vancomycin. Sequence analysis of
      the E. faecalis genome indicated that (p)ppGpp synthesis is catalyzed by the
      bifunctional synthetase/hydrolase RelA and the RelQ small synthase. The (p)ppGpp
      profiles of DeltarelA, DeltarelQ, and DeltarelAQ strains revealed that RelA is
      the major enzyme responsible for the accumulation of (p)ppGpp during antibiotic
      or physical stresses, while RelQ appears to be responsible for maintaining basal
      levels of alarmone during homeostatic growth. Compared to its parent, the
      DeltarelA strain was more susceptible to several stress conditions, whereas
      complete elimination of (p)ppGpp in a DeltarelAQ double mutant restored many of
      the stress-sensitive phenotypes of DeltarelA. Interestingly, growth curves and
      time-kill studies indicated that tolerance to vancomycin is enhanced in the
      DeltarelA strain but diminished in the DeltarelQ and DeltarelAQ strains. Finally,
      virulence of the DeltarelAQ strain but not of the DeltarelA or DeltarelQ strain
      was significantly attenuated in the Caenorhabditis elegans model. Taken together,
      these results indicate that (p)ppGpp pools modulate environmental stress
      responses, vancomycin tolerance, and virulence in this important nosocomial
      pathogen.

PMID- 19168609
TI  - A novel integrative conjugative element mediates genetic transfer from group G
      Streptococcus to other {beta}-hemolytic Streptococci.
AB  - Lateral gene transfer is a significant contributor to the ongoing evolution of
      many bacterial pathogens, including beta-hemolytic streptococci. Here we provide
      the first characterization of a novel integrative conjugative element (ICE),
      ICESde3396, from Streptococcus dysgalactiae subsp. equisimilis (group G
      streptococcus [GGS]), a bacterium commonly found in the throat and skin of
      humans. ICESde3396 is 64 kb in size and encodes 66 putative open reading frames.
      ICESde3396 shares 38 open reading frames with a putative ICE from Streptococcus
      agalactiae (group B streptococcus [GBS]), ICESa2603. In addition to genes
      involves in conjugal processes, ICESde3396 also carries genes predicted to be
      involved in virulence and resistance to various metals. A major feature of
      ICESde3396 differentiating it from ICESa2603 is the presence of an 18-kb internal
      recombinogenic region containing four unique gene clusters, which appear to have
      been acquired from streptococcal and nonstreptococcal bacterial species. The four
      clusters include two cadmium resistance operons, an arsenic resistance operon,
      and genes with orthologues in a group A streptococcus (GAS) prophage.
      Streptococci that naturally harbor ICESde3396 have increased resistance to
      cadmium and arsenate, indicating the functionality of genes present in the 18-kb
      recombinogenic region. By marking ICESde3396 with a kanamycin resistance gene, we
      demonstrate that the ICE is transferable to other GGS isolates as well as GBS and
      GAS. To investigate the presence of the ICE in clinical streptococcal isolates,
      we screened 69 isolates (30 GGS, 19 GBS, and 20 GAS isolates) for the presence of
      three separate regions of ICESde3396. Eleven isolates possessed all three
      regions, suggesting they harbored ICESde3396-like elements. Another four isolates
      possessed ICESa2603-like elements. We propose that ICESde3396 is a mobile genetic
      element that is capable of acquiring DNA from multiple bacterial sources and is a
      vehicle for dissemination of this DNA through the wider beta-hemolytic
      streptococcal population.

PMID- 19168610
TI  - Complete genome sequence of Erythrobacter litoralis HTCC2594.
AB  - Erythrobacter litoralis has been known as a bacteriochlorophyll a-containing,
      aerobic, anoxygenic, phototrophic bacterium. Here we announce the complete genome
      sequence of E. litoralis HTCC2594, which is devoid of phototrophic potential. E.
      litoralis HTCC2594, isolated by dilution-to-extinction culturing from seawater,
      could not carry out aerobic anoxygenic phototrophy and lacked genes for
      bacteriochlorophyll a biosynthesis and photosynthetic reaction center proteins.

PMID- 19168611
TI  - Maturation of the translation inhibitor microcin C.
AB  - Microcin C (McC), an inhibitor of the growth of enteric bacteria, consists of a
      heptapeptide with a modified AMP residue attached to the backbone of the C
      terminal aspartate through an N-acyl phosphamidate bond. Here we identify
      maturation intermediates produced by cells lacking individual mcc McC
      biosynthesis genes. We show that the products of the mccD and mccE genes are
      required for attachment of a 3-aminopropyl group to the phosphate of McC and that
      this group increases the potency of inhibition of the McC target, aspartyl-tRNA
      synthetase.

PMID- 19168612
TI  - Roles of Agrobacterium tumefaciens RirA in iron regulation, oxidative stress
      response, and virulence.
AB  - The analysis of genetics and physiological functions of Agrobacterium tumefaciens
      RirA (rhizobial iron regulator) has shown that it is a transcription regulator
      and a repressor of iron uptake systems. The rirA mutant strain (NTLrirA)
      overproduced siderophores and exhibited a highly constitutive expression of genes
      involved in iron uptake (fhuA, irp6A, and fbpA) compared to that of the wild-type
      strain (NTL4). The deregulation in the iron control of iron uptake in NTLrirA led
      to iron overload in the cell, which was supported by the observation that the
      NTLrirA mutant was more sensitive than wild-type NTL4 to an iron-activated
      antibiotic, streptonigrin. The NTLrirA mutant was more sensitive than the
      parental strain to oxidants, including hydrogen peroxide, organic hydroperoxide,
      and a superoxide generator, menadione. However, the addition of an iron chelator,
      2,2'-dipyridyl, reversed the mutant hypersensitivity to H(2)O(2) and organic
      hydroperoxide, indicating the role of iron in peroxide toxicity. Meanwhile, the
      reduced level of superoxide dismutase (SodBIII) was partly responsible for the
      menadione-sensitive phenotype of the NTLrirA mutant. The NTLrirA mutant showed a
      defect in tumorigenesis on tobacco leaves, which likely resulted from the
      increased sensitivity of NTLrirA to oxidants and the decreased ability of NTLrirA
      to induce virulence genes (virB and virE). These data demonstrated that RirA is
      important for A. tumefaciens during plant-pathogen interactions.

PMID- 19168613
TI  - Transcriptional regulation of the cellobiose operon of Streptococcus mutans.
AB  - The ability of Streptococcus mutans to catabolize cellobiose, a beta-linked
      glucoside generated during the hydrolysis of cellulose, is shown to be regulated
      by a transcriptional regulator, CelR, which is encoded by an operon with a
      phospho-beta-glucosidase (CelA) and a cellobiose-specific sugar
      phosphotransferase system (PTS) permease (EII(Cel)). The roles of CelR, EII(Cel)
      components, and certain fructose/mannose-PTS permeases in the transcriptional
      regulation of the cel locus were analyzed. The results revealed that (i) the celA
      and celB (EIIB(Cel)) gene promoters require CelR for transcriptional activation
      in response to cellobiose, but read-through from the celA promoter contributes to
      expression of the EII(Cel) genes; (ii) the EII(Cel) subunits were required for
      growth on cellobiose and for transcriptional activation of the cel genes; (iii)
      CcpA plays little direct role in catabolite repression of the cel regulon, but
      loss of specific PTS permeases alleviated repression of cel genes in the presence
      of preferred carbohydrates; and (iv) glucose could induce transcription of the
      cel regulon when transported by EII(Cel). CelR derivatives containing amino acid
      substitutions for five conserved histidine residues in two PTS regulatory domains
      and an EIIA-like domain also provided important insights regarding the function
      of this regulator. Based on these data, a model for the involvement of PTS
      permeases and the general PTS proteins enzyme I and HPr was developed that
      reveals a critical role for the PTS in CcpA-independent catabolite repression and
      induction of cel gene expression in S. mutans.

PMID- 19168614
TI  - Three-dimensional macromolecular organization of cryofixed Myxococcus xanthus
      biofilms as revealed by electron microscopic tomography.
AB  - Despite the fact that most bacteria grow in biofilms in natural and pathogenic
      ecosystems, very little is known about the ultrastructure of their component
      cells or about the details of their community architecture. We used high-pressure
      freezing and freeze-substitution to minimize the artifacts of chemical fixation,
      sample aggregation, and sample extraction. As a further innovation we have, for
      the first time in biofilm research, used electron tomography and three
      dimensional (3D) visualization to better resolve the macromolecular 3D
      ultrastructure of a biofilm. This combination of superb specimen preparation and
      greatly improved resolution in the z axis has opened a window in studies of
      Myxococcus xanthus cell ultrastructure and biofilm community architecture. New
      structural information on the chromatin body, cytoplasmic organization, membrane
      apposition between adjacent cells, and structure and distribution of pili and
      vesicles in the biofilm matrix is presented.

PMID- 19168615
TI  - Genetic analysis of the invariant residue G791 in Escherichia coli 16S rRNA
      implicates RelA in ribosome function.
AB  - Previous studies identified G791 in Escherichia coli 16S rRNA as an invariant
      residue for ribosome function. In order to establish the functional role of this
      residue in protein synthesis, we searched for multicopy suppressors of the mutant
      ribosomes that bear a G-to-U substitution at position 791. We identified relA, a
      gene whose product has been known to interact with ribosomes and trigger a
      stringent response. Overexpression of RelA resulted in the synthesis of
      approximately 1.5 times more chloramphenicol acetyltransferase (CAT) protein than
      could be synthesized by the mutant ribosomes in the absence of RelA
      overexpression. The ratio of mutant rRNA to the total ribosome pool was not
      changed, and the steady-state level of CAT mRNA was decreased by RelA
      overexpression. These data confirmed that the phenotype of RelA as a multicopy
      suppressor of the mutant ribosome did not result from the enhanced synthesis of
      mutant rRNA or CAT mRNA from the plasmid. To test whether the phenotype of RelA
      was related to the stringent response induced by the increased cellular level of
      (p)ppGpp, we screened for mutant RelA proteins whose overexpression enhances CAT
      protein synthesis by the mutant ribosomes as effectively as wild-type RelA
      overexpression and then screened for those whose overexpression does not produce
      sufficiently high levels of (p)ppGpp to trigger the stringent response under the
      condition of amino acid starvation. Overexpression of the isolated mutant RelA
      proteins resulted in the accumulation of (p)ppGpp in cells, which was amounted to
      approximately 18.2 to 38.9% of the level of (p)ppGpp found in cells that
      overexpress the wild-type RelA. These findings suggest that the function of RelA
      as a multicopy suppressor of the mutant ribosome does not result from its
      (p)ppGpp synthetic activity. We conclude that RelA has a previously unrecognized
      role in ribosome function.

PMID- 19168616
TI  - Psychrobacter arcticus 273-4 uses resource efficiency and molecular motion
      adaptations for subzero temperature growth.
AB  - Permafrost soils are extreme environments that exert low-temperature,
      desiccation, and starvation stress on bacteria over thousands to millions of
      years. To understand how Psychrobacter arcticus 273-4 survived for >20,000 years
      in permafrost, transcriptome analysis was performed during growth at 22 degrees
      C, 17 degrees C, 0 degrees C, and -6 degrees C using a mixed-effects analysis of
      variance model. Genes for transcription, translation, energy production, and most
      biosynthetic pathways were downregulated at low temperatures. Evidence of isozyme
      exchange was detected over temperature for D-alanyl-D-alanine carboxypeptidases
      (dac1 and dac2), DEAD-box RNA helicases (csdA and Psyc_0943), and energy
      efficient substrate incorporation pathways for ammonium and acetate. Specific
      functions were compensated by upregulation of genes at low temperature, including
      genes for the biosynthesis of proline, tryptophan, and methionine. RNases and
      peptidases were generally upregulated at low temperatures. Changes in energy
      metabolism, amino acid metabolism, and RNase gene expression were consistent with
      induction of a resource efficiency response. In contrast to results observed for
      other psychrophiles and mesophiles, only clpB and hsp33 were upregulated at low
      temperature, and there was no upregulation of other chaperones and peptidyl
      prolyl isomerases. relA, csdA, and dac2 knockout mutants grew more slowly at low
      temperature, but a dac1 mutant grew more slowly at 17 degrees C. The combined
      data suggest that the basal biological machinery, including translation,
      transcription, and energy metabolism, is well adapted to function across the
      growth range of P. arcticus from -6 degrees C to 22 degrees C, and temperature
      compensation by gene expression was employed to address specific challenges to
      low-temperature growth.

PMID- 19168617
TI  - The Thermotoga maritima Trk potassium transporter--from frameshift to function.
AB  - The gene for the Thermotoga maritima Trk potassium transporter component TrkA was
      originally thought to be a frameshift mutation and not to encode a functional
      protein. However, expression from this gene yielded a complex consisting of two
      distinct proteins designated TM1088A and -B. Genetic complementation of
      Escherichia coli mutants unable to transport potassium suggests that TM1088A/B is
      part of a functional Trk potassium transporter complex with the membrane protein
      TM1089. The protein structure for TM1088A shows a characteristic Rossmann fold
      indicating an NAD+ binding site and has structural similarity to potassium
      channel-related proteins. Ligand binding studies indicated that ATP, ADP, and AMP
      stabilized TM1088A to a much greater degree than NADH and NAD, consistent with
      the crystal structure of TM1088A, which contains a bound AMP natural ligand at
      the characteristic GXGXXG nucleotide binding site. Mutation of single and all
      glycines at this nucleotide binding site eliminated in vitro protein
      stabilization by the ligand, yet these mutated proteins could still functionally
      complement the E. coli potassium uptake mutants. We predict that this new two
      subunit class of TrkA proteins is present in a number of organisms. A further
      subclass of the predicted two-subunit TrkA proteins lack an identifiable membrane
      spanning subunit of the Trk K+ transporter. This class, as exemplified by
      Mycobacterium tuberculosis, did not complement E. coli potassium transport with
      the native E. coli TrkH; thus, it may require a novel TrkH-like protein for
      activity or provide an alternate function in vivo.

PMID- 19168618
TI  - An intact urease assembly pathway is required to compete with NikR for nickel
      ions in Helicobacter pylori.
AB  - We examined the effects of urease and hydrogenase assembly gene deletions on NikR
      activation in H. pylori strains 26695 and G27. The loss of any component of
      urease assembly increased NikR activity under Ni2+-limiting conditions, as
      measured by reduced transcript levels and 63Ni accumulation. Additionally, SlyD
      functioned in urease assembly in strain 26695.

PMID- 19168619
TI  - Copper acquisition is mediated by YcnJ and regulated by YcnK and CsoR in Bacillus
      subtilis.
AB  - Copper is an essential cofactor for many enzymes, and at over a threshold level,
      it is toxic for all organisms. To understand the mechanisms underlying copper
      homeostasis of the gram-positive bacterium Bacillus subtilis, we have performed
      microarray studies under copper-limiting conditions. These studies revealed that
      the ycnJ gene encodes a protein that plays an important role in copper
      metabolism, as it shows a significant, eightfold upregulation under copper
      limiting conditions and its disruption causes a growth-defective phenotype under
      copper deprivation as well as a reduced intracellular content of copper. Native
      gel shift experiments with the periplasmic N-terminal domain of the YcnJ membrane
      protein (135 residues) disclosed its strong affinity to Cu(II) ions in vitro.
      Inspection of the upstream sequence of ycnJ revealed that the ycnK gene encodes a
      putative transcriptional regulator, whose deletion caused an elevated expression
      of ycnJ, especially under conditions of copper excess. Further studies
      demonstrated that the recently identified copper efflux regulator CsoR also is
      involved in the regulation of ycnJ expression, leading to a new model for copper
      homeostasis in B. subtilis.

PMID- 19168620
TI  - Pneumolysin localizes to the cell wall of Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is the causative agent of multiple diseases, including
      otitis media, pneumonia, bacteremia, and meningitis. Pneumolysin (Ply), a member
      of the cholesterol-dependent cytolytic pore-forming toxins, is produced by
      virtually all clinical isolates of S. pneumoniae, and strains in which the Ply
      gene has been deleted are severely attenuated in mouse models of infection. In
      contrast to all other members of the cholesterol-dependent cytolysin family, Ply
      lacks a signal peptide for export. Instead, Ply has been hypothesized to be
      released upon autolysis or, alternatively, via a nonautolytic mechanism that
      remains ill defined. We determined by use of cell fractionation and Western
      blotting that, during in vitro growth, exported Ply is localized primarily to the
      cell wall compartment in 18 different serotypes in the absence of detectable cell
      lysis. Hemolytic assays revealed that this cell wall-localized Ply is active.
      Additionally, cell wall-localized Ply is accessible to extracellular protease and
      is detergent releasable.

PMID- 19168621
TI  - The Pseudomonas aeruginosa sensor kinase KinB negatively controls alginate
      production through AlgW-dependent MucA proteolysis.
AB  - Mucoidy, or overproduction of the exopolysaccharide known as alginate, in
      Pseudomonas aeruginosa is a poor prognosticator for lung infections in cystic
      fibrosis. Mutation of the anti-sigma factor MucA is a well-accepted mechanism for
      mucoid conversion. However, certain clinical mucoid strains of P. aeruginosa have
      a wild-type (wt) mucA. Here, we describe a loss-of-function mutation in kinB that
      causes overproduction of alginate in the wt mucA strain PAO1. KinB is the cognate
      histidine kinase for the transcriptional activator AlgB. Increased alginate
      production due to inactivation of kinB was correlated with high expression at the
      alginate-related promoters P(algU) and P(algD). Deletion of alternative sigma
      factor RpoN (sigma(54)) or the response regulator AlgB in kinB mutants decreased
      alginate production to wt nonmucoid levels. Mucoidy was restored in the kinB algB
      double mutant by expression of wt AlgB or phosphorylation-defective AlgB.D59N,
      indicating that phosphorylation of AlgB was not required for alginate
      overproduction when kinB was inactivated. The inactivation of the DegS-like
      protease AlgW in the kinB mutant caused loss of alginate production and an
      accumulation of the hemagglutinin (HA)-tagged MucA. Furthermore, we observed that
      the kinB mutation increased the rate of HA-MucA degradation. Our results also
      indicate that AlgW-mediated MucA degradation required algB and rpoN in the kinB
      mutant. Collectively, these studies indicate that KinB is a negative regulator of
      alginate production in wt mucA strain PAO1.

PMID- 19168622
TI  - Overexpression of MazFsa in Staphylococcus aureus induces bacteriostasis by
      selectively targeting mRNAs for cleavage.
AB  - The role of chromosomally encoded toxin-antitoxin (TA) loci in bacterial
      physiology has been under debate, with the toxin proposed as either an inducer of
      bacteriostasis or a mediator of programmed cell death (PCD). We report here that
      ectopic expression of MazF(Sa), a toxin of the TA module from Staphylococcus
      aureus, led to a rapid decrease in CFU counts but most cells remained viable as
      determined by differential Syto 9 and propidium iodide staining after MazF(Sa)
      induction. This finding suggested that the toxin MazF(Sa) induced cell stasis
      rather than cell death. We also showed that MazF(Sa) selectively cleaves cellular
      mRNAs in vivo, avoiding "important" transcripts such as recA, gyrB, and sarA
      mRNAs in MazF(Sa)-induced cells, while these three mRNAs can be cleaved in vitro.
      The results of Northwestern blotting showed that both sarA and recA mRNAs bind
      strongly to a putative RNA-binding protein. These data suggest that S. aureus
      likely undergoes stasis by protecting selective mRNA with RNA-binding proteins
      upon the expression of MazF(Sa) in vivo.

PMID- 19168624
TI  - Conformational toggle switches implicated in basal constitutive and agonist
      induced activated states of 5-hydroxytryptamine-4 receptors.
AB  - The extended classic ternary complex model predicts that a G protein-coupled
      receptor (GPCR) exists in only two interconvertible states: an inactive R, and an
      active R(*). However, different structural active R(*) complexes may exist in
      addition to a silent inactive R ground state (Rg). Here we demonstrate, in a
      cellular context, that several R(*) states of 5-hydroxytryptamine-4 (5-HT(4))
      receptors involve different side-chain conformational toggle switches. Using site
      directed mutagenesis and molecular modeling approaches, we show that the basal
      constitutive receptor (R(*)basal) results from stabilization of an obligatory
      double toggle switch (Thr3.36 from inactive g- to active g+ and Trp6.48 from
      inactive g+ to active t). Mutation of either threonine or tryptophan to alanine
      resulted in a lowering of the activity of the R(*)basal similar to the Rg. The
      T3.36A mutation shows that the Thr3.36 toggle switch plays a minor role in the
      stabilization of R(*) induced by 5-HT (R(*)-5-HT) and BIMU8 (R(*)-BIMU8) and is
      fully required in the stabilization of R(*) induced by (S)-zacopride, cisapride,
      and 1-(4-amino-5-chloro-2-methoxyphenyl)-3-(1-butyl-4-piperidinyl)-1-propanone
      (RS 67333) (R(*)-benzamides). Thus, benzamides stabilize R(*)-benzamides by
      forming a specific hydrogen bond with Thr3.36 in the active g+ conformation.
      Conversely, R(*)-BIMU8 was probably the result of a direct conformational
      transition of Trp6.48 from inactive g+ to active t by hydrogen bonding of this
      residue to a carboxyl group of BIMU8. We were surprised that the Trp6.48 toggle
      switch was not necessary for receptor activation by the natural agonist 5-HT.
      R(*)-5-HT is probably attained through other routes of activation. Thus,
      different conformational arrangements occur during stabilization of R(*)basal,
      R(*)-5-HT, R(*)-benzamides, and R(*)-BIMU8.

PMID- 19168623
TI  - The Sac10b homolog in Methanococcus maripaludis binds DNA at specific sites.
AB  - The Sac10b protein family, also known as Alba, is widely distributed in Archaea.
      Sac10b homologs in thermophilic Sulfolobus species are very abundant. They bind
      both DNA and RNA with high affinity and without sequence specificity, and their
      physiological functions are still not fully understood. Mma10b from the
      euryarchaeote Methanococcus maripaludis is a mesophilic member of the Sac10b
      family. Mma10b is not abundant and constitutes only approximately 0.01% of the
      total cellular protein. Disruption of mma10b resulted in poor growth of the
      mutant in minimal medium at near the optimal growth temperature but had no
      detectable effect on growth in rich medium. Quantitative proteomics, real time
      reverse transcription-PCR, and enzyme assays revealed that the expression levels
      of some genes involved in CO(2) assimilation and other activities were changed in
      the Deltamma10b mutant. Chromatin immunoprecipitation suggested a direct
      association of Mma10b with an 18-bp DNA binding motif in vivo. Electrophoretic
      mobility shift assays and DNase I footprinting confirmed that Mma10b
      preferentially binds specific sequences of DNA with an apparent Kd in the 100 nM
      range. These results suggested that the physiological role of Mma10b in the
      mesophilic methanococci is greatly diverged from that of homologs in
      thermophiles.

PMID- 19168625
TI  - Monoamine oxidase A gene (MAOA) predicts behavioral aggression following
      provocation.
AB  - Monoamine oxidase A gene (MAOA) has earned the nickname "warrior gene" because it
      has been linked to aggression in observational and survey-based studies. However,
      no controlled experimental studies have tested whether the warrior gene actually
      drives behavioral manifestations of these tendencies. We report an experiment,
      synthesizing work in psychology and behavioral economics, which demonstrates that
      aggression occurs with greater intensity and frequency as provocation is
      experimentally manipulated upwards, especially among low activity MAOA (MAOA-L)
      subjects. In this study, subjects paid to punish those they believed had taken
      money from them by administering varying amounts of unpleasantly hot (spicy)
      sauce to their opponent. There is some evidence of a main effect for genotype and
      some evidence for a gene by environment interaction, such that MAOA is less
      associated with the occurrence of aggression in a low provocation condition, but
      significantly predicts such behavior in a high provocation situation. This new
      evidence for genetic influences on aggression and punishment behavior complicates
      characterizations of humans as "altruistic" punishers and supports theories of
      cooperation that propose mixed strategies in the population. It also suggests
      important implications for the role of individual variance in genetic factors
      contributing to everyday behaviors and decisions.

PMID- 19168626
TI  - An unrecognized extracellular function for an intracellular adapter protein
      released from the cytoplasm into the tumor microenvironment.
AB  - Mammalian cell membranes provide an interface between the intracellular and
      extracellular compartments. It is currently thought that cytoplasmic signaling
      adapter proteins play no functional role within the extracellular tumor
      environment. Here, by selecting combinatorial random peptide libraries in tumor
      bearing mice, we uncovered a direct, specific, and functional interaction between
      CRKL, an adapter protein [with Src homology 2 (SH2)- and SH3-containing domains],
      and the plexin-semaphorin-integrin domain of beta(1) integrin in the
      extracellular milieu. Through assays in vitro, in cellulo, and in vivo, we show
      that this unconventional and as yet unrecognized protein-protein interaction
      between a regulatory integrin domain (rather than a ligand-binding one) and an
      intracellular adapter (acting outside of the cells) triggers an alternative
      integrin-mediated cascade for cell growth and survival. Based on these data, here
      we propose that a secreted form of the SH3/SH2 adaptor protein CRKL may act as a
      growth-promoting factor driving tumorigenesis and may lead to the development of
      cancer therapeutics targeting secreted CRKL.

PMID- 19168627
TI  - MicroRNAs as modulators of smoking-induced gene expression changes in human
      airway epithelium.
AB  - We have shown that smoking impacts bronchial airway gene expression and that
      heterogeneity in this response associates with smoking-related disease risk. In
      this study, we sought to determine whether microRNAs (miRNAs) play a role in
      regulating the airway gene expression response to smoking. We examined whole
      genome miRNA and mRNA expression in bronchial airway epithelium from current and
      never smokers (n = 20) and found 28 miRNAs to be differentially expressed (P <
      0.05) with the majority being down-regulated in smokers. We further identified a
      number of mRNAs whose expression level is highly inversely correlated with miRNA
      expression in vivo. Many of these mRNAs contain potential binding sites for the
      differentially expressed miRNAs in their 3'-untranslated region (UTR) and are
      themselves affected by smoking. We found that either increasing or decreasing the
      levels of mir-218 (a miRNA that is strongly affected by smoking) in both primary
      bronchial epithelial cells and H1299 cells was sufficient to cause a
      corresponding decrease or increase in the expression of predicted mir-218 mRNA
      targets, respectively. Further, mir-218 expression is reduced in primary
      bronchial epithelium exposed to cigarette smoke condensate (CSC), and alteration
      of mir-218 levels in these cells diminishes the induction of the predicted mir
      218 target MAFG in response to CSC. These data indicate that mir-218 levels
      modulate the airway epithelial gene expression response to cigarette smoke and
      support a role for miRNAs in regulating host response to environmental toxins.

PMID- 19168628
TI  - Export of RNA silencing from C. elegans tissues does not require the RNA channel
      SID-1.
AB  - Double-stranded RNA (dsRNA) triggers RNA interference (RNAi) to silence genes of
      matching sequence. In some animals this experimentally induced silencing is
      transported between cells, and studies in the nematode Caenorhabditis elegans
      have shown that the dsRNA channel SID-1 is required for the import of such
      transported silencing signals. Gene silencing can also be triggered by
      endogenously expressed RNAi triggers, but it is unknown whether such silencing is
      transported between cells. Here, we show that, in C. elegans, SID-1 is required
      for efficient silencing of multicopy transgenes, indicating that mobile silencing
      signals contribute to transgene silencing. Further, most tissues can transport
      silencing initiated by the tissue-specific transgenic expression of RNAi triggers
      to other tissues, consistent with expressed RNAi triggers generating mobile
      silencing signals. Whereas the import of silencing signals requires SID-1, we
      found that mobile silencing signals generated by transgene-expressed RNAi
      triggers are exported to other tissues through a SID-1-independent mechanism.
      Furthermore, when RNAi triggers are expressed in ingested Escherichia coli,
      silencing signals can be transported to internal tissues from the gut lumen
      across gut cells that lack SID-1. Thus, C. elegans can transport endogenous and
      exogenous RNA silencing signals between many different tissues via at least 2 SID
      1 independent export pathways.

PMID- 19168629
TI  - Antibody to Langerin/CD207 localizes large numbers of CD8alpha+ dendritic cells
      to the marginal zone of mouse spleen.
AB  - Dendritic cells (DCs) are strategically positioned to take up antigens and
      initiate adaptive immunity. One DC subset expresses CD8alphaalpha in mice and is
      specialized to capture dying cells and process antigens for MHC class I "cross
      presentation." Because CD8(+) DCs also express DEC205/CD205, which is localized
      to splenic T cell regions, it is thought that CD8(+) DCs also are restricted to T
      zones. Here, we used a new antibody to Langerin/CD207, which colabels isolated
      CD8(+) CD205(+) DCs, to immunolabel spleen sections. The mAb labeled discrete
      cells with high levels of CD11c and CD8. Surprisingly most CD207(+) profiles were
      in marginal zones surrounding splenic white pulp nodules, and only smaller
      numbers were in T cell areas, where CD205 colabeling was noted. Despite a
      marginal zone location, CD207(+) DCs lacked identifying molecules for 3 different
      types of macrophages, localized in proximity and, in contrast to macrophages,
      marginal zone DCs were poor scavengers of soluble and particulate substrates.
      After stimulation with microbial agonists, Langerin expression disappeared from
      the marginal zone at 6-12 h, but was greatly expanded in the T cell areas, and by
      24-48 h, Langerin expression disappeared. Therefore, anti-Langerin antibodies
      localize a majority of CD8(+) DCs to non-T cell regions of mouse spleen, where
      they are distinct from adjacent macrophages.

PMID- 19168630
TI  - Behavioral experiments on biased voting in networks.
AB  - Many distributed collective decision-making processes must balance diverse
      individual preferences with a desire for collective unity. We report here on an
      extensive session of behavioral experiments on biased voting in networks of
      individuals. In each of 81 experiments, 36 human subjects arranged in a virtual
      network were financially motivated to reach global consensus to one of two
      opposing choices. No payments were made unless the entire population reached a
      unanimous decision within 1 min, but different subjects were paid more for
      consensus to one choice or the other, and subjects could view only the current
      choices of their network neighbors, thus creating tensions between private
      incentives and preferences, global unity, and network structure. Along with
      analyses of how collective and individual performance vary with network structure
      and incentives generally, we find that there are well-studied network topologies
      in which the minority preference consistently wins globally; that the presence of
      "extremist" individuals, or the awareness of opposing incentives, reliably
      improve collective performance; and that certain behavioral characteristics of
      individual subjects, such as "stubbornness," are strongly correlated with
      earnings.

PMID- 19168631
TI  - Duplicate genes increase expression diversity in closely related species and
      allopolyploids.
AB  - Polyploidy or whole genome duplication (WGD) provides raw genetic materials for
      sequence and expression evolution of duplicate genes. However, the mode and tempo
      of expression divergence between WGD duplicate genes in closely related species
      and recurrent allopolyploids are poorly understood. Arabidopsis is a suitable
      system for testing the hypothesis that duplicate genes increase expression
      diversity and regulatory networks. In Arabidopsis, WGD occurred more than once
      before the split between Arabidopsis thaliana and Arabidopsis arenosa, and both
      natural and human-made allotetraploids are available. Comparative genomic
      hybridization analysis indicated that single-copy and duplicate genes after WGD
      were well preserved in A. thaliana and A. arenosa. Analysis of gene expression
      microarrays showed that duplicate genes generally had higher levels of expression
      divergence between two closely related species than single-copy genes. The
      proportion of the progenitors' duplicate genes that were nonadditively expressed
      in the resynthesized and natural allotetraploids was significantly higher than
      that of single-copy genes. Duplicate genes related to environmental stresses
      tended to be differentially expressed, and multicopy duplicate genes were likely
      to diverge expression between progenitors and in the allotetraploids. Compared
      with single-copy genes, duplicate genes tended to contain TATA boxes and less DNA
      methylation in the promoter regions, facilitating transcriptional regulation by
      binding transcription factors and/or cis- and trans-acting proteins. The data
      suggest an important role of WGD duplicate genes in modulating diverse and novel
      gene expression changes in response to external environmental cues and internal
      genetic turmoil such as recurrent polyploidy events.

PMID- 19168632
TI  - Structure-based mechanism of lipoteichoic acid synthesis by Staphylococcus aureus
      LtaS.
AB  - Staphylococcus aureus synthesizes polyglycerol-phosphate lipoteichoic acid (LTA)
      from phosphatidylglycerol. LtaS, a predicted membrane protein with 5 N-terminal
      transmembrane helices followed by a large extracellular part (eLtaS), is required
      for staphylococcal growth and LTA synthesis. Here, we report the first crystal
      structure of the eLtaS domain at 1.2-A resolution and show that it assumes a
      sulfatase-like fold with an alpha/beta core and a C-terminal part composed of 4
      anti-parallel beta-strands and a long alpha-helix. Overlaying eLtaS with
      sulfatase structures identified active site residues, which were confirmed by
      alanine substitution mutagenesis and in vivo enzyme function assays. The
      cocrystal structure with glycerol-phosphate and the coordination of a Mn(2+)
      cation allowed us to propose a reaction mechanism, whereby the active site
      threonine of LtaS functions as nucleophile for phosphatidylglycerol hydrolysis
      and formation of a covalent threonine-glycerolphosphate intermediate. These
      results will aid in the development of LtaS-specific inhibitors for S. aureus and
      many other Gram-positive pathogens.

PMID- 19168633
TI  - Multiple transcription factor codes activate epidermal wound-response genes in
      Drosophila.
AB  - Wounds in Drosophila and mouse embryos induce similar genetic pathways to repair
      epidermal barriers. However, the transcription factors that transduce wound
      signals to repair epidermal barriers are largely unknown. We characterize the
      transcriptional regulatory enhancers of 4 genes-Ddc, ple, msn, and kkv-that are
      rapidly activated in epidermal cells surrounding wounds in late Drosophila
      embryos and early larvae. These epidermal wound enhancers all contain
      evolutionarily conserved sequences matching binding sites for JUN/FOS and GRH
      transcription factors, but vary widely in trans- and cis-requirements for these
      inputs and their binding sites. We propose that the combination of GRH and FOS is
      part of an ancient wound-response pathway still used in vertebrates and
      invertebrates, but that other mechanisms have evolved that result in similar
      transcriptional output. A common, but largely untested assumption of
      bioinformatic analyses of gene regulatory networks is that transcription units
      activated in the same spatial and temporal patterns will require the same cis
      regulatory codes. Our results indicate that this is an overly simplistic view.

PMID- 19168634
TI  - Stoichiometry of molecular complexes at adhesions in living cells.
AB  - We describe a method to detect molecular complexes and measure their
      stoichiometry in living cells from simultaneous fluctuations of the fluorescence
      intensity in two image channels, each detecting a different kind of protein. The
      number and brightness (N&B) analysis, namely, the use of the ratio between the
      variance and the average intensity to obtain the brightness of molecules, is
      extended to the cross-variance of the intensity fluctuations in two channels. We
      apply the cross-variance method to determine the stoichiometry of complexes
      containing paxillin and vinculin or focal adhesion kinase (FAK) in disassembling
      adhesions in mouse embryo fibroblasts expressing FAK, vinculin, and paxillin
      tagged with EGFP and mCherry. We found no complexes of these proteins in the
      cytoplasm away from the adhesions. However, at the adhesions, large aggregates
      leave, forming a hole, during their disassembly. This hole shows cross
      correlation between FAK and paxillin and vinculin and paxillin. From the
      amplitude of the correlated fluctuations we determine the composition of the
      aggregates leaving the adhesions. These aggregates disassemble rapidly in the
      cytoplasm because large complexes are found only in very close proximity to the
      adhesions or at their borders.

PMID- 19168635
TI  - Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor
      induced mobilization of circulating angiogenic cells.
AB  - Using a cell-based reporter gene assay, we screened a library of drugs in
      clinical use and identified the anthracycline chemotherapeutic agents doxorubicin
      and daunorubicin as potent inhibitors of hypoxia-inducible factor 1 (HIF-1)
      mediated gene transcription. These drugs inhibited HIF-1 by blocking its binding
      to DNA. Daily administration of doxorubicin or daunorubicin potently inhibited
      the transcription of a HIF-1-dependent reporter gene as well as endogenous HIF-1
      target genes encoding vascular endothelial growth factor, stromal-derived factor
      1, and stem cell factor in tumor xenografts. CXCR4(+)/sca1(+), VEGFR2(+)/CD34(+),
      and VEGFR2(+)/CD117(+) bone-marrow derived cells were increased in the peripheral
      blood of SCID mice bearing prostate cancer xenografts but not in tumor-bearing
      mice treated for 5 days with doxorubicin or daunorubicin, which dramatically
      reduced tumor vascularization. These results provide a molecular basis for the
      antiangiogenic effect of anthracycline therapy and have important implications
      for refining the use of these drugs to treat human cancer more effectively.

PMID- 19168636
TI  - Vacuolar transport of nicotine is mediated by a multidrug and toxic compound
      extrusion (MATE) transporter in Nicotiana tabacum.
AB  - Alkaloids play a key role in plant defense mechanisms against pathogens and
      herbivores, but the plants themselves need to cope with their toxicity as well.
      The major alkaloid of the Nicotiana species, nicotine, is translocated via xylem
      transport from the root tissues where it is biosynthesized to the accumulation
      sites, the vacuoles of leaves. To unravel the molecular mechanisms behind this
      membrane transport, we characterized one transporter, the tobacco (Nicotiana
      tabacum) jasmonate-inducible alkaloid transporter 1 (Nt-JAT1), whose expression
      was coregulated with that of nicotine biosynthetic genes in methyl jasmonate
      treated tobacco cells. Nt-JAT1, belonging to the family of multidrug and toxic
      compound extrusion transporters, was expressed in roots, stems, and leaves, and
      localized in the tonoplast of leaf cells. When produced in yeast cells, Nt-JAT1
      occurred mainly in the plasma membrane and showed nicotine efflux activity.
      Biochemical analysis with proteoliposomes reconstituted with purified Nt-JAT1 and
      bacterial F(0)F(1)-ATPase revealed that Nt-JAT1 functioned as a proton antiporter
      and recognized endogenous tobacco alkaloids, such as nicotine and anabasine, and
      other alkaloids, such as hyoscyamine and berberine, but not flavonoids. These
      findings strongly suggest that Nt-JAT1 plays an important role in the nicotine
      translocation by acting as a secondary transporter responsible for unloading of
      alkaloids in the aerial parts and deposition in the vacuoles.

PMID- 19168637
TI  - Substance use disorders in perpetrators of intimate partner violence in a
      forensic setting.
AB  - This study investigates the point prevalence of substance use disorders in 150
      perpetrators of intimate partner violence (IPV) in a forensic setting and
      compares participants with and without substance use disorders on demographic and
      offence-related variables. Furthermore, it investigates the frequency of IPV
      perpetrated under the influence of substances. Half the sample (50.0%) meets
      diagnostic criteria for at least one substance-related diagnosis. Significantly
      more IPV perpetrators without substance use disorders compared with IPV
      perpetrators with substance use disorders have children living at home and have
      abused their children. Relative to IPV perpetrators without substance use
      disorders, significantly more IPV perpetrators with substance-related disorders
      are found to be under the influence of substances at the time of the offence.
      Results highlight the importance of understanding the prevalence of substance use
      disorders in IPV perpetrators in forensic settings.

PMID- 19168638
TI  - Study characteristics and recidivism base rates in juvenile sex offender
      recidivism.
AB  - This study reports on the results of a review and meta-analysis of 63 data sets
      that examine sexual recidivism among juvenile sex offenders. The studies include
      a total of 11,219 juvenile sex offenders, followed for a weighted mean of 59.4
      months (SD = 36.1 months). Recidivism is identified through official records of
      arrest or conviction. The weighted mean sexual recidivism rate is 7.08% ( SD =
      3.9%). The weighted mean rate of general recidivism is 43.4% ( SD = 18.9%).
      Studies that examine sexual recidivism during adolescence find monthly sexual
      recidivism rates that are more than 4 times higher than those found in studies
      that rely only on adult recidivism records. Neither the level of secured
      placement (community, residential, or secured custody) nor the use of arrest
      versus conviction as an outcome significantly influences sexual recidivism rates.

PMID- 19168639
TI  - Prospective actuarial risk assessment: a comparison of five risk assessment
      instruments in different sexual offender subtypes.
AB  - This study examines the predictive validity of the most commonly used risk
      assessment instruments for sexual offenders: Static-99, Rapid Risk Assessment for
      Sexual Offense Recidivism, Sex Offender Risk Appraisal Guide, Sexual Violence
      Risk-20, and Psychopathy Checklist-Revised in a prospective research design.
      Although risk assessment is part of a regime leading to various efforts to reduce
      risk by treatment and aftercare, all instruments show good predictive validity.
      However, depending on the instrument, recidivism category, and subgroup, the
      predictive accuracy varies markedly. Furthermore, the authors fail to demonstrate
      predictive validity for sexual violent reoffences-for the whole sample and for
      all subgroups. The results, nevertheless, support the utility and predictive
      validity of actuarial risk assessment complementary to treatment efforts to
      reduce risk. On the other hand, forensic practitioners have to be aware of the
      limitations of actuarial risk assessment methods, in particular as regards to
      variable predictive accuracy for different sexual offender subgroups and
      reoffence categories.

PMID- 19168641
TI  - Diel growth cycle of isolated leaf discs analyzed with a novel, high-throughput
      three-dimensional imaging method is identical to that of intact leaves.
AB  - Dicot leaves grow with pronounced diel (24-h) cycles that are controlled by a
      complex network of factors. It is an open question to what extent leaf growth
      dynamics are controlled by long-range or by local signals. To address this
      question, we established a stereoscopic imaging system, GROWSCREEN 3D, which
      quantifies surface growth of isolated leaf discs floating on nutrient solution in
      wells of microtiter plates. A total of 458 leaf discs of tobacco (Nicotiana
      tabacum) were cut at different developmental stages, incubated, and analyzed for
      their relative growth rates. The camera system was automatically displaced across
      the array of leaf discs; visualization and camera displacement took about 12 s
      for each leaf disc, resulting in a time interval of 1.5 h for consecutive size
      analyses. Leaf discs showed a comparable diel leaf growth cycle as intact leaves
      but weaker peak growth activity. Hence, it can be concluded that the timing of
      leaf growth is regulated by local rather than by systemic control processes. This
      conclusion was supported by results from leaf discs of Arabidopsis (Arabidopsis
      thaliana) Landsberg erecta wild-type plants and starch-free1 mutants. At night,
      utilization of transitory starch leads to increased growth of Landsberg erecta
      wild-type discs compared with starch-free1 discs. Moreover, the decrease of leaf
      disc growth when exposed to different concentrations of glyphosate showed an
      immediate dose-dependent response. Our results demonstrate that a dynamic leaf
      disc growth analysis as we present it here is a promising approach to uncover the
      effects of internal and external cues on dicot leaf development.

PMID- 19168640
TI  - Proteins from multiple metabolic pathways associate with starch biosynthetic
      enzymes in high molecular weight complexes: a model for regulation of carbon
      allocation in maize amyloplasts.
AB  - Starch biosynthetic enzymes from maize (Zea mays) and wheat (Triticum aestivum)
      amyloplasts exist in cell extracts in high molecular weight complexes; however,
      the nature of those assemblies remains to be defined. This study tested the
      interdependence of the maize enzymes starch synthase IIa (SSIIa), SSIII, starch
      branching enzyme IIb (SBEIIb), and SBEIIa for assembly into multisubunit
      complexes. Mutations that eliminated any one of those proteins also prevented the
      others from assembling into a high molecular mass form of approximately 670 kD,
      so that SSIII, SSIIa, SBEIIa, and SBEIIb most likely all exist together in the
      same complex. SSIIa, SBEIIb, and SBEIIa, but not SSIII, were also interdependent
      for assembly into a complex of approximately 300 kD. SSIII, SSIIa, SBEIIa, and
      SBEIIb copurified through successive chromatography steps, and SBEIIa, SBEIIb,
      and SSIIa coimmunoprecipitated with SSIII in a phosphorylation-dependent manner.
      SBEIIa and SBEIIb also were retained on an affinity column bearing a specific
      conserved fragment of SSIII located outside of the SS catalytic domain.
      Additional proteins that copurified with SSIII in multiple biochemical methods
      included the two known isoforms of pyruvate orthophosphate dikinase (PPDK), large
      and small subunits of ADP-glucose pyrophosphorylase, and the sucrose synthase
      isoform SUS-SH1. PPDK and SUS-SH1 required SSIII, SSIIa, SBEIIa, and SBEIIb for
      assembly into the 670-kD complex. These complexes may function in global
      regulation of carbon partitioning between metabolic pathways in developing seeds.

PMID- 19168642
TI  - Positive fluorescent selection permits precise, rapid, and in-depth
      overexpression analysis in plant protoplasts.
AB  - Transient genetic modification of plant protoplasts is a straightforward and
      rapid technique for the study of numerous aspects of plant biology. Recent
      studies in metazoan systems have utilized cell-based assays to interrogate signal
      transduction pathways using high-throughput methods. Plant biologists could
      benefit from new tools that expand the use of cell culture for large-scale
      analysis of gene function. We have developed a system that employs fluorescent
      positive selection in combination with flow cytometric analysis and fluorescence
      activated cell sorting to isolate responses in the transformed protoplasts
      exclusively. The system overcomes the drawback that transfected protoplast
      suspensions are often a heterogeneous mix of cells that have and have not been
      successfully transformed. This Gateway-compatible system enables high-throughput
      screening of genetic circuitry using overexpression. The incorporation of a red
      fluorescent protein selection marker enables combined utilization with widely
      available green fluorescent protein (GFP) tools. For instance, such a dual
      labeling approach allows cytometric analysis of GFP reporter gene activation
      expressly in the transformed cells or fluorescence-activated cell sorting
      mediated isolation and downstream examination of overexpression effects in a
      specific GFP-marked cell population. Here, as an example, novel uses of this
      system are applied to the study of auxin signaling, exploiting the red
      fluorescent protein/GFP dual labeling capability. In response to manipulation of
      the auxin response network through overexpression of dominant negative auxin
      signaling components, we quantify effects on auxin-responsive DR5::GFP reporter
      gene activation as well as profile genome-wide transcriptional changes
      specifically in cells expressing a root epidermal marker.

PMID- 19168643
TI  - Nitric oxide contributes to cadmium toxicity in Arabidopsis by promoting cadmium
      accumulation in roots and by up-regulating genes related to iron uptake.
AB  - Nitric oxide (NO) functions as a cell-signaling molecule in plants. In
      particular, a role for NO in the regulation of iron homeostasis and in the plant
      response to toxic metals has been proposed. Here, we investigated the synthesis
      and the role of NO in plants exposed to cadmium (Cd(2+)), a nonessential and
      toxic metal. We demonstrate that Cd(2+) induces NO synthesis in roots and leaves
      of Arabidopsis (Arabidopsis thaliana) seedlings. This production, which is
      sensitive to NO synthase inhibitors, does not involve nitrate reductase and
      AtNOA1 but requires IRT1, encoding a major plasma membrane transporter for iron
      but also Cd(2+). By analyzing the incidence of NO scavenging or inhibition of its
      synthesis during Cd(2+) treatment, we demonstrated that NO contributes to Cd(2+)
      triggered inhibition of root growth. To understand the mechanisms underlying this
      process, a microarray analysis was performed in order to identify NO-modulated
      root genes up- and down-regulated during Cd(2+) treatment. Forty-three genes were
      identified encoding proteins related to iron homeostasis, proteolysis, nitrogen
      assimilation/metabolism, and root growth. These genes include IRT1. Investigation
      of the metal and ion contents in Cd(2+)-treated roots in which NO synthesis was
      impaired indicates that IRT1 up-regulation by NO was consistently correlated to
      NO's ability to promote Cd(2+) accumulation in roots. This analysis also
      highlights that NO is responsible for Cd(2+)-induced inhibition of root Ca(2+)
      accumulation. Taken together, our results suggest that NO contributes to Cd(2+)
      toxicity by favoring Cd(2+) versus Ca(2+) uptake and by initiating a cellular
      pathway resembling those activated upon iron deprivation.

PMID- 19168644
TI  - Molecular and functional characterization of PEBP genes in barley reveal the
      diversification of their roles in flowering.
AB  - Five barley (Hordeum vulgare) PEBP (for phosphatidylethanolamine-binding protein)
      genes were analyzed to clarify their functional roles in flowering using
      transgenic, expression, and quantitative trait locus analyses. Introduction of
      HvTFL1 and HvMFT1 into rice (Oryza sativa) plants did not result in any changes
      in flowering, suggesting that these two genes have functions distinct from
      flowering. Overexpression of HvFT1, HvFT2, and HvFT3 in rice resulted in early
      heading, indicating that these FT-like genes can act as promoters of the floral
      transition. HvFT1 transgenic plants showed the most robust flowering initiation.
      In barley, HvFT1 was expressed at the time of shoot meristem phase transition.
      These results suggest that HvFT1 is the key gene responsible for flowering in the
      barley FT-like gene family. HvFT2 transgenic plants also showed robust flowering
      initiation, but HvFT2 was expressed only under short-day (SD) conditions during
      the phase transition, suggesting that its role is limited to specific
      photoperiodic conditions in barley. Flowering activity in HvFT3 transgenic rice
      was not as strong and was modulated by the photoperiod. These results suggest
      that HvFT3 functions in flowering promotion but that its effect is indirect.
      HvFT3 expression was observed in Morex, a barley cultivar carrying a dominant
      allele of Ppd-H2, a major quantitative trait locus for flowering under SD
      conditions, although no expression was detected in Steptoe, a cultivar carrying
      ppd-H2. HvFT3 was expressed in Morex under both long-day and SD conditions,
      although its expression was increased under SD conditions. HvFT3 was mapped to
      chromosome 1HL, the same chromosome that carries Ppd-H2. Genomic sequence
      analyses revealed that Morex possesses an intact HvFT3 gene, whereas most of this
      gene has been lost in Steptoe. These data strongly suggest that HvFT3 may be
      identical to Ppd-H2.

PMID- 19168645
TI  - The signal peptide peptidase is required for pollen function in Arabidopsis.
AB  - The Signal Peptide Peptidases (SPP) are members of the Intramembrane Cleaving
      Proteases, which are involved in an array of protein-processing and intracellular
      signaling events in animals. Arabidopsis (Arabidopsis thaliana) has six genes
      encoding SPP-like proteins, the physiological functions of which are unknown. As
      a first step in defining the roles of the SPPs in plants, we examined the
      distribution and activities of Arabidopsis SPP (AtSPP; accession no. At2g03120),
      the SPP-like gene with the highest degree of similarity to human SPP. The
      protease is expressed at low levels throughout the plant, with the highest levels
      in emerging leaves, roots, and floral tissues. Homozygous plants carrying a T-DNA
      insertion mutation in AtSPP, spp-2, could not be recovered, and transmission of
      the mutant allele through pollen was reduced to less than 2% in reciprocal cross
      experiments. Although viable, pollen from spp-2 heterozygous plants exhibited a
      50% reduction in germination rate and a disruption in male germ unit
      organization. These data demonstrate that AtSPP is required for male gametophyte
      development and pollen maturation in Arabidopsis.

PMID- 19168646
TI  - Changes in barotolerance, thermotolerance, and cellular morphology throughout the
      life cycle of Listeria monocytogenes.
AB  - Changes in barotolerance, thermotolerance, and cellular morphology throughout the
      life cycle of Listeria monocytogenes were investigated. For part 1 of this
      analysis, L. monocytogenes ATCC 19115 was grown to log, stationary, death, and
      long-term-survival phases at 35 degrees C in tryptic soy broth with yeast extract
      (TSBYE). Cells were diluted in whole milk that had been subjected to ultrahigh
      temperatures (UHT whole milk) and then high-pressure processed (HPP) at 400 MPa
      for 180 s or thermally processed at 62.8 degrees C for 30 s. As cells
      transitioned from the log to the long-term-survival phase, the D(400 MPa) and
      D(62.8 degrees C) values increased 10- and 19-fold, respectively. Cells decreased
      in size as they transitioned from the log to the long-term-survival phase. Rod
      shaped cells transitioned to cocci as they entered the late-death and long-term
      survival phases. L. monocytogenes strains F5069 and Scott A showed similar
      results. For part 2 of the analysis, cells in long-term-survival phase were
      centrifuged, suspended in fresh TSBYE, and incubated at 35 degrees C. As cells
      transitioned from the long-term-survival phase to log and the stationary phase,
      they increased in size and log reductions increased following HPP or heat
      treatment. In part 3 of this analysis, cells in long-term-survival phase were
      centrifuged, suspended in UHT whole milk, and incubated at 4 degrees C. After HPP
      or heat treatment, similar results were observed as for part 2. We hypothesize
      that cells of L. monocytogenes enter a dormant, long-term-survival phase and
      become more barotolerant and thermotolerant due to cytoplasmic condensation when
      they transition from rods to cocci. Further research is needed to test this
      hypothesis and to determine the practical significance of these findings.

PMID- 19168647
TI  - Comparative analysis of attachment of Shiga-toxigenic Escherichia coli and
      Salmonella strains to cultured HT-29 and Caco-2 cell lines.
AB  - The ability of Escherichia coli and Salmonella isolates to attach to Caco-2 and
      HT-29 cell monolayers was measured. All isolates displayed a greater ability to
      attach to Caco-2 cells than HT-29 cells, and overall E. coli isolates attached
      better to both cell lines than Salmonella isolates. Bacteria that were considered
      to be pathogenic displayed no greater ability to attach to cell lines than those
      that were not considered to be pathogenic. Additionally, no correlation was found
      between cell line attachment and previously determined hydrophobicity results.

PMID- 19168649
TI  - Longitudinal study of Shiga toxin-producing Escherichia coli shedding in sheep
      feces: persistence of specific clones in sheep flocks.
AB  - To provide information on the persistence and maintenance of colonization with
      Shiga toxin-producing Escherichia coli (STEC) in sheep, pulsed-field gel
      electrophoresis analysis of STEC isolates (n = 145) belonging to serogroups O5,
      O91, and O146 from 39 healthy animals was performed in a 12-month longitudinal
      study carried out with four sheep flocks. At the flock level as well as the
      individual-animal level, the same clones were obtained on sampling occasions
      separated by as much as 11 months.

PMID- 19168650
TI  - Nickel promotes biofilm formation by Escherichia coli K-12 strains that produce
      curli.
AB  - The survival of bacteria exposed to toxic compounds is a multifactorial
      phenomenon, involving well-known molecular mechanisms of resistance but also less
      well-understood mechanisms of tolerance that need to be clarified. In particular,
      the contribution of biofilm formation to survival in the presence of toxic
      compounds, such as nickel, was investigated in this study. We found that a
      subinhibitory concentration of nickel leads Escherichia coli bacteria to change
      their lifestyle, developing biofilm structures rather than growing as free
      floating cells. Interestingly, whereas nickel and magnesium both alter the global
      cell surface charge, only nickel promotes biofilm formation in our system.
      Genetic evidence indicates that biofilm formation induced by nickel is mediated
      by the transcriptional induction of the adhesive curli-encoding genes. Biofilm
      formation induced by nickel does not rely on efflux mechanisms using the RcnA
      pump, as these require a higher concentration of nickel to be activated. Our
      results demonstrate that the nickel-induced biofilm formation in E. coli is an
      adaptational process, occurring through a transcriptional effect on genes coding
      for adherence structures. The biofilm lifestyle is obviously a selective
      advantage in the presence of nickel, but the means by which it improves bacterial
      survival needs to be investigated.

PMID- 19168651
TI  - Phage-mediated Shiga toxin 2 gene transfer in food and water.
AB  - Shiga toxin (stx) transduction in various food matrices has been evaluated with
      lysogens of Stx phages. stx transduction events were observed for many phages
      under appropriate conditions. Transduction did not occur at low pH and low
      temperatures. A total of 10(3) to 10(4) CFU ml(-1) was the minimal amount of
      donor and recipient strains necessary to generate transductants.

PMID- 19168652
TI  - Exploring the diversity of the bifidobacterial population in the human intestinal
      tract.
AB  - Although the health-promoting roles of bifidobacteria are widely accepted, the
      diversity of bifidobacteria among the human intestinal microbiota is still poorly
      understood. We performed a census of bifidobacterial populations from human
      intestinal mucosal and fecal samples by plating them on selective medium, coupled
      with molecular analysis of selected rRNA gene sequences (16S rRNA gene and
      internally transcribed spacer [ITS] 16S-23S spacer sequences) of isolated
      colonies. A total of 900 isolates were collected, of which 704 were shown to
      belong to bifidobacteria. Analyses showed that the culturable bifidobacterial
      population from intestinal and fecal samples include six main phylogenetic taxa,
      i.e., Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium
      adolescentis, Bifidobacterium pseudolongum, Bifidobacterium breve, and
      Bifidobacterium bifidum, and two species mostly detected in fecal samples, i.e.,
      Bifidobacterium dentium and Bifidobacterium animalis subp. lactis. Analysis of
      bifidobacterial distribution based on age of the subject revealed that certain
      identified bifidobacterial species were exclusively present in the adult human
      gut microbiota whereas others were found to be widely distributed. We encountered
      significant intersubject variability and composition differences between fecal
      and mucosa-adherent bifidobacterial communities. In contrast, a modest
      diversification of bifidobacterial populations was noticed between different
      intestinal regions within the same individual (intrasubject variability).
      Notably, a small number of bifidobacterial isolates were shown to display a wide
      ecological distribution, thus suggesting that they possess a broad colonization
      capacity.

PMID- 19168653
TI  - C29 olefinic hydrocarbons biosynthesized by Arthrobacter species.
AB  - Arthrobacter aurescens TC1, Arthrobacter chlorophenolicus A6, Arthrobacter
      crystallopoietes, and Arthrobacter oxydans produce long-chain monoalkenes,
      predominantly cis-3,25-dimethyl-13-heptacosene. Four other Arthrobacter strains
      did not form alkenes. The level of cis-3,25-dimethyl-13-heptacosene in
      Arthrobacter chlorophenolicus A6 remained proportional to cell mass during
      growth. cis-3,25-Dimethyl-13-heptacosene did not support growth of A.
      chlorophenolicus A6.

PMID- 19168654
TI  - Interaction between lactic acid bacteria and Mycobacterium bovis in Ethiopian
      fermented milk: insight into the fate of M. bovis.
AB  - Mycobacterium bovis causes tuberculosis in animals and humans. Infected cows can
      transmit the bacillus to humans via milk. Milk also contains lactic acid bacteria
      (LAB). LAB isolated from milk were put in milk cultures together with spiked M.
      bovis. Different LAB had different abilities to reduce M. bovis counts, as M.
      bovis was undetectable in some while it persisted in two of the cultures.

PMID- 19168655
TI  - The Salmonella pathogenicity island 2-encoded type III secretion system is
      essential for the survival of Salmonella enterica serovar Typhimurium in free
      living amoebae.
AB  - Free-living amoebae represent a potential reservoir and predator of Salmonella
      enterica. Through the use of type III secretion system (T3SS) mutants and
      analysis of transcription of selected T3SS genes, we demonstrated that the
      Salmonella pathogenicity island 2 is highly induced during S. enterica serovar
      Typhimurium infection of Acanthamoeba polyphaga and is essential for survival
      within amoebae.

PMID- 19168656
TI  - Tetracycline resistome of the organic pig gut.
AB  - The occurrence of genes conferring resistance to tetracyclines in the organic pig
      gut was assessed through the metagenomic approach. Of 9,000 bacterial artificial
      chromosome clones analyzed, 10 were identified as carrying the known tet(C),
      tet(W), and tet(40) genes, as well as novel genes encoding resistance to the
      tetracyclines minocycline and doxycycline. The latter are different from the
      known tet genes and are homologous to genes encoding UDP-glucose 4-epimerases,
      with the domain structure characteristic for these enzymes. The majority of the
      resistance genes were associated with putative mobile genetic elements. The
      sequence of a novel 9.7-kb plasmid carrying tet(W) and tet(40) was also
      identified. Conserved flanking regions identified around the tet(W) and tet(40)
      genes in our metagenomic library may play a role in genetic exchange of these
      genes. This is the first report describing the occurrence of tet(40) outside the
      human intestine. The maintenance of antibiotic resistance genes in apparently
      antibiotic-free animals is probably due to their presence on mobile genetic
      elements, the fitness cost of which for the cell is ameliorated during the
      previous antibiotic selection.

PMID- 19168657
TI  - Studies of the production of fungal polyketides in Aspergillus nidulans by using
      systems biology tools.
AB  - Many filamentous fungi produce polyketide molecules with great significance as
      human pharmaceuticals; these molecules include the cholesterol-lowering compound
      lovastatin, which was originally isolated from Aspergillus terreus. The chemical
      diversity and potential uses of these compounds are virtually unlimited, and it
      is thus of great interest to develop a well-described microbial production
      platform for polyketides. Using genetic engineering tools available for the model
      organism Aspergillus nidulans, we constructed two recombinant strains, one
      expressing the Penicillium griseofulvum 6-methylsalicylic acid (6-MSA) synthase
      gene and one expressing the 6-MSA synthase gene and overexpressing the native
      xylulose-5-phosphate phosphoketolase gene (xpkA) for increasing the pool of
      polyketide precursor levels. The physiology of the recombinant strains and that
      of a reference wild-type strain were characterized on glucose, xylose, glycerol,
      and ethanol media in controlled bioreactors. Glucose was found to be the
      preferred carbon source for 6-MSA production, and 6-MSA concentrations up to 455
      mg/liter were obtained for the recombinant strain harboring the 6-MSA gene. Our
      findings indicate that overexpression of xpkA does not directly improve 6-MSA
      production on glucose, but it is possible, if the metabolic flux through the
      lower part of glycolysis is reduced, to obtain quite high yields for conversion
      of sugar to 6-MSA. Systems biology tools were employed for in-depth analysis of
      the metabolic processes. Transcriptome analysis of 6-MSA-producing strains grown
      on glucose and xylose in the presence and absence of xpkA overexpression,
      combined with flux and physiology data, enabled us to propose an xpkA-msaS
      interaction model describing the competition between biomass formation and 6-MSA
      production for the available acetyl coenzyme A.

PMID- 19168658
TI  - Reconfiguring the quorum-sensing regulator SdiA of Escherichia coli to control
      biofilm formation via indole and N-acylhomoserine lactones.
AB  - SdiA is a homolog of quorum-sensing regulators that detects N-acylhomoserine
      lactone (AHL) signals from other bacteria. Escherichia coli uses SdiA to reduce
      its biofilm formation in the presence of both AHLs and its own signal indole.
      Here we reconfigured SdiA (240 amino acids) to control biofilm formation using
      protein engineering. Four SdiA variants were obtained with altered biofilm
      formation, including truncation variants SdiA1E11 (F7L, F59L, Y70C, M94K, and
      K153X) and SdiA14C3 (W9R, P49T, N87T, frameshift at N96, and L123X), which
      reduced biofilm formation by 5- to 20-fold compared to wild-type SdiA in the
      presence of endogenous indole. Whole-transcriptome profiling revealed that wild
      type SdiA reduced biofilm formation by repressing genes related to indole
      synthesis and curli synthesis compared to when no SdiA was expressed, while
      variant SdiA1E11 induced genes related to indole synthesis in comparison to wild
      type SdiA. These results suggested altered indole metabolism, and corroborating
      the DNA microarray results in regard to indole synthesis, variant SdiA1E11
      produced ninefold more indole, which led to reduced swimming motility and cell
      density. Also, wild-type SdiA decreased curli production and tnaA transcription,
      while SdiA1E11 increased tnaA transcription (tnaA encodes tryptophanase, which
      forms indole) compared to wild-type SdiA. Hence, wild-type SdiA decreased biofilm
      formation by reducing curli production and motility, and SdiA1E11 reduced biofilm
      formation via indole. Furthermore, an AHL-sensitive variant (SdiA2D10, having
      four mutations at E31G, Y42F, R116H, and L165Q) increased biofilm formation
      sevenfold in the presence of N-octanoyl-DL-homoserine lactone and N-(3
      oxododecatanoyl)-L-homoserine lactone. Therefore, SdiA can be evolved to increase
      or decrease biofilm formation, and biofilm formation may be controlled by
      altering sensors rather than signals.

PMID- 19168660
TI  - Diffusion of macromolecules in model oral biofilms.
AB  - The diffusive penetration of fluorescently tagged macromolecular solutes into
      model oral biofilms was visualized by time-lapse microscopy. All of the solutes
      tested, including dextrans, proteases, green fluorescent protein, and
      immunoglobulin G, accessed the interior of cell clusters 100 to 200 microm in
      diameter within 3 min or less.

PMID- 19168659
TI  - Real-time PCR assay for detection of a new simulant for poxvirus biothreat
      agents.
AB  - Research and financial efforts spent on biodefense technologies highlight the
      current concern for biothreat event preparedness. Nonhazardous but relevant
      "simulant" microorganisms are typically used to simplify technological
      developments, testing, and staff training. The bacteriophage MS2, a small RNA
      virus, is classically used as the reference simulant for biothreat viruses within
      the biodefense community. However, variola virus, considered a major threat,
      displays very different features (size, envelope, and double-stranded DNA
      genome). The size parameter is critical for aerosol sampling, detection, and
      protection/filtration technologies. Therefore, a panel of relevant simulants
      should be used to cover the diversity of biothreat agents. Thus, we investigated
      a new virus model, the Cydia pomonella granulovirus (baculovirus), which is
      currently used as a biopesticide. It displays a size similar to that of
      poxviruses, is enveloped, and contains double-stranded DNA. To provide a
      molecular tool to detect and quantify this model virus, we developed an assay
      based on real-time PCR, with a limit of detection ranging from roughly 10 to a
      few tens of target copies per microl according to the sample matrix. The
      specificity of the assay against a large panel of potential cross-reactive
      microorganisms was checked, and the suitability of the assay for environmental
      samples, especially aerosol studies, was determined. In conclusion, we suggest
      that our PCR assay allows Cydia pomonella granulovirus to be used as a simulant
      for poxviruses. This assay may also be useful for environmental or crop treatment
      studies.

PMID- 19168661
TI  - Development of a prophage typing system and analysis of prophage carriage in
      Streptococcus pneumoniae.
AB  - The frequency of prophage carriage was tested in a collection of 108 clinical
      isolates of Streptococcus pneumoniae. A PCR-based assay was developed to allow
      classification of the prophage into the three groups recently identified
      according to genome comparisons (P. Romero, N. Croucher, N. L. Hiller, F. Z. Hu,
      G. D. Ehrlich, S. D. Bentley, E. Garcia, and T. J. Mitchell, submitted for
      publication). Use of the assay showed that more than half of the isolates studied
      were lysogenic with prophage belonging to group 1 being the most abundant (56%),
      followed by those belonging to group 2 (26%) and those belonging to group 3
      (11%). Four polylysogenic strains harboring a group 1 and a group 2 prophage were
      identified. Interestingly, lysogenic strains were found in 8 out of the 12
      internationally distributed, relevant clones of S. pneumoniae contained in our
      strain collection. The high percentage of clinical pneumococcal isolates
      harboring prophage strongly suggests an important contribution to the
      diversification of the genome architecture in this species as well as a role for
      bacteriophage in the virulence/and or fitness of S. pneumoniae, although further
      studies using a significant number of isolates belonging to the most relevant
      pneumococcal clones are needed.

PMID- 19168662
TI  - Inverse mapping the neuronal substrates of face categorizations.
AB  - Face perception is a complex process involving a network of brain structures,
      dynamically processing information to enable judgments about a face to be made
      (e.g., familiarity, identity, and expression). Here we introduce an analysis
      methodology that makes it possible to directly study this information processing
      in the brain from spatially and temporally resolved magnetoencephalographic
      signals. We apply our methodology to the study of 2 face categorization tasks,
      gender and expressiveness, and track the processing of 3 key visual features that
      underlie behavioral performance, over time and throughout the cortex. We find
      information processing correlates beginning from 90 ms following stimulus onset,
      where features are processed in isolation in occipital extrastriate regions. Over
      time, processing of successively more features and feature combinations takes
      place in occipitotemporal regions, with maximal information processing of visual
      information coinciding with the well-established face-selective M170 component at
      170 ms. Later still, around 250-400 ms, cortical activity responds significantly
      more to task-specific features and their complex combinations. These results
      indicate a complex process of visual information processing during face
      perception with face parts processed in isolation at very early stages, and task
      specific processing of combinations of features taking place within 300 ms.
      Crucially, our approach specifically establishes which information in the visual
      stimulus the brain signal is responding to and how this varies with time,
      cortical location, and task demands to establish a more precise tracking of
      information processing mechanisms in the cortex during face perception.

PMID- 19168663
TI  - Overlap and segregation in predorsal premotor cortex activations related to free
      selection of self-referenced and target-based finger movements.
AB  - In reaching movements, parietal contributions can be distinguished that are based
      on representations of external space and body scheme. By functional magnetic
      resonance imaging, we examined 16 healthy subjects to see whether such
      segregation similarly exists in the frontal lobes when visuomotor actions are not
      specified but when free choices are allowed. Free selection was button based
      (target based) or finger based (self-referenced), with invariant instructions as
      control. To avoid a visual attention bias, instructions were auditory presented.
      Statistical parametric mapping revealed that free button selection with the same
      finger was associated with increased activations in the anterior cingulate cortex
      (ACC), right posterodorsal prefrontal cortex (PFC) including the rostral
      extension of the dorsal premotor cortex (pre-PMd), and the anterodorsal PFC.
      Prefrontal activation related to free finger selection (pressing the same button)
      was restricted to an anteromedial segment of the posterodorsal PFC/pre-PMd.
      Bilateral inferior parietal activations were present in both free-choice
      conditions. Pre-PMd and parietal contributions to free selection support concepts
      on early-stage action selection in dorsal visuomotor pathways. The rostral-caudal
      segregation in pre-PMd activations reflected that in anterior direction, frontal
      processing is gradually less involved in selection of environmental information
      but increasingly committed to self-referenced selection. ACC particularly
      contributes to free selection between external goals.

PMID- 19168664
TI  - Proteomic analysis illuminates a novel structural definition of the claustrum and
      insula.
AB  - The claustrum is a prominent but ill-defined forebrain structure that has been
      suggested to integrate multisensory information and perhaps transform percepts
      into consciousness. The claustrum's shape and vague borders have hampered
      experimental assessment of its functions. We used matrix-assisted laser
      desorption ionization-imaging mass spectrometry to reveal a novel protein marker,
      G-protein gamma2 subunit (Gng2), which is enriched in the claustrum but not
      adjacent structures of the rat forebrain. The spatial pattern of Gng2 expression
      suggests key differences from commonly held views of the claustrum's structure.
      Using anatomical methods, we found that the rat claustrum is present only at
      striatal levels of the telencephalon and does not extend to frontal cortical
      territories. Moreover, the claustrum is surrounded on all sides by layer VI
      insular cortex cells in both the rat and primate. Using these defining
      characteristics of the claustrum, we found that the claustrum projects to
      cortical but not to subcortical sites. The definition of the claustrum as a
      cortical site is considered. The identification of a claustrum-specific protein
      opens the door to selective molecular lesions and the subsequent evaluation of
      the role of the claustrum in cognition.

PMID- 19168665
TI  - Intermediate neuronal progenitors (basal progenitors) produce pyramidal
      projection neurons for all layers of cerebral cortex.
AB  - The developing cerebral cortex contains apical and basal types of neurogenic
      progenitor cells. Here, we investigated the cellular properties and neurogenic
      output of basal progenitors, also called intermediate neuronal progenitors
      (INPs). We found that basal mitoses expressing transcription factor Tbr2 (an INP
      marker) were present throughout corticogenesis, from embryonic day 10.5 through
      birth. Postnatally, Tbr2(+) progenitors were present in the dentate gyrus,
      subventricular zone (SVZ), and posterior periventricle (pPV). Two morphological
      subtypes of INPs were distinguished in the embryonic cortex, "short radial" in
      the ventricular zone (VZ) and multipolar in the SVZ, probably corresponding to
      molecularly defined INP subtypes. Unexpectedly, many short radial INPs appeared
      to contact the apical (ventricular) surface and some divided there. Time-lapse
      video microscopy suggested that apical INP divisions produced daughter INPs.
      Analysis of neurogenic divisions (Tis21-green fluorescent protein [GFP](+))
      indicated that INPs may produce the majority of projection neurons for preplate,
      deep, and superficial layers. Conversely, proliferative INP divisions (Tis21-GFP(
      )) increased from early to middle corticogenesis, concomitant with SVZ growth.
      Our findings support the hypothesis that regulated amplification of INPs may be
      an important factor controlling the balance of neurogenesis among different
      cortical layers.

PMID- 19168666
TI  - Double dissociation between motor and visual imagery in the posterior parietal
      cortex.
AB  - Because motor imagery (MI) and visual imagery (VI) are influenced differently by
      factors such as biomechanical constraints or stimulus size, it is conceivable
      that they rely on separate processes, possibly involving distinct cortical
      networks, a view corroborated by neuroimaging and neuropsychological studies. In
      the posterior parietal cortex, it has been suggested that the superior parietal
      lobule (SPL) underlies VI, whereas MI relies on the supramarginalis gyrus (SMG).
      However, because several brain imaging studies have also shown an overlap of
      activations in SPL and SMG during VI or MI, the question arises as to which
      extent these 2 subregions really contribute to distinct imagery processes. To
      address this issue, we used repetitive transcranial magnetic stimulation to
      induce virtual lesions of either SMG or SPL in subjects performing a MI (hand
      drawing rotation) or a VI (letter rotation) task. Whatever hemisphere was
      stimulated, SMG lesions selectively altered MI, whereas SPL lesions only affected
      VI, demonstrating a double dissociation between MI and VI. Because these deficits
      were not influenced by the angular distance of the stimuli, we suggest that SMG
      and SPL are involved in the reenactment of the motor and visual representations,
      respectively, and not in mental rotation processes per se.

PMID- 19168667
TI  - Damage to white matter fiber tracts in acute spatial neglect.
AB  - Previous statistical voxelwise lesion-behavior mapping (VLBM) studies have
      demonstrated that spatial neglect is associated with cortical and subcortical
      gray matter damage. However, it has also been suggested that the disorder may
      result from white matter injury. Our aim was to investigate the white matter
      connectivity in a large sample of 140 stroke patients. We combined a VLBM
      approach with the histological maps of the human white matter fiber tracts
      provided by the Julich probabilistic cytoarchitectonic atlas. We found that
      damage of right perisylvian white matter connections-the superior longitudinal
      fasciculus, the inferior occipitofrontal fasciculus, and the superior
      occipitofrontal fasciculus-is a typical finding in patients with spatial neglect.
      However, the analysis also revealed that the largest portion of the lesion area,
      namely between 89.1% and 96.6%, affected brain structures other than the
      perisylvian white matter fiber tracts. Predominantly, these included gray matter
      structures such as the superior temporal, inferior parietal, inferior frontal,
      and insular cortices, as well as subcortically the putamen and the caudate
      nucleus. Damage of gray matter structures thus appears to be a strong predictor
      of spatial neglect.

PMID- 19168668
TI  - Molecular regulators of phosphate homeostasis in plants.
AB  - An appropriate cellular phosphate (Pi) concentration is indispensable for
      essential physiological and biochemical processes. To maintain cellular Pi
      homeostasis, plants have developed a series of adaptive responses to facilitate
      external Pi acquisition and to limit Pi consumption and to adjust Pi recycling
      internally when the Pi supply is inadequate. Over the past decade, significant
      progress has been made toward understanding such regulation at the molecular
      level. In this review, the focus is on the molecular regulators that mediate
      cellular Pi concentrations. The regulators are introduced and organized according
      to their original identification procedures, by the forward genetic approach of
      mutant screening or by reverse genetic analysis. These genes are involved in Pi
      uptake, allocation or remobilization or are upstream regulators, such as
      transcriptional factors or signalling molecules. In the future, integration of
      current knowledge and exploration of new technology is expected to offer new
      insights into molecular mechanisms that maintain Pi homeostasis.

PMID- 19168669
TI  - Recognition of comorbid diabetes and obesity in hospital records of newly
      diagnosed cancer patients.

PMID- 19168670
TI  - A phase II trial of cisplatin (C), gemcitabine (G) and gefitinib for advanced
      urothelial tract carcinoma: results of Cancer and Leukemia Group B (CALGB) 90102.
AB  - BACKGROUND: This phase II trial (Cancer and Leukemia Group B 90102) sought to
      determine the efficacy of cisplatin, standard infusion of gemcitabine and
      gefitinib in patients with advanced urothelial carcinoma. PATIENTS AND METHODS:
      Eligible patients had previously untreated measurable disease, Eastern
      Cooperative Oncology Group (ECOG) performance status of zero to two and
      creatinine clearance >50 ml/min. Treatment consisted of cisplatin 70 mg/m(2) day
      1 and gemcitabine 1000 mg/m(2) on days 1 and 8 given every 3 weeks concurrent
      with gefitinib 500 mg/day orally for six cycles. Maintenance gefitinib 500 mg/day
      was continued for responding or stable disease. RESULTS: Fifty-four of 58
      patients were assessable. Twelve patients (22%) had node-only disease, and 25
      (46%) had an ECOG performance status of zero. There were 23 objective responses
      for an overall response rate of 42.6% [95% confidence interval (CI) 29.2% to
      56.8%]. The median survival time was 15.1 months (95% CI 11.1-21.7 months) and
      the median time to progression was 7.4 months (95% CI 5.6-9.2 months).
      CONCLUSIONS: The combination of cisplatin, gemcitabine and gefitinib is well
      tolerated and active in advanced transitional cell carcinoma. The addition of
      gefitinib does not appear to improve response rate or survival in comparison to
      historical controls of cisplatin and gemcitabine alone.

PMID- 19168671
TI  - CD5 expression in de novo diffuse large B-cell lymphomas.

PMID- 19168673
TI  - The cell migration molecule UNC-53/NAV2 is linked to the ARP2/3 complex by ABI-1.
AB  - The shape changes that are required to position a cell to migrate or grow out in
      a particular direction involve a coordinated reorganization of the actin
      cytoskeleton. Although it is known that the ARP2/3 complex nucleates actin
      filament assembly, exactly how the information from guidance cues is integrated
      to elicit ARP2/3-mediated remodeling during outgrowth remains vague. Previous
      studies have shown that C. elegans UNC-53 and its vertebrate homolog NAV
      (Neuronal Navigators) are required for the migration of cells and neuronal
      processes. We have identified ABI-1 as a novel molecular partner of UNC-53/NAV2
      and have found that a restricted calponin homology (CH) domain of UNC-53 is
      sufficient to bind ABI-1. ABI-1 and UNC-53 have an overlapping expression
      pattern, and display similar cell migration phenotypes in the excretory cell, and
      in mechanosensory and motoneurons. Migration defects were also observed after
      RNAi of proteins known to function with abi-1 in actin dynamics, including nck-1,
      wve-1 and arx-2. We propose that UNC-53/NAV2, through its CH domain, acts as a
      scaffold that links ABI-1 to the ARP2/3 complex to regulate actin cytoskeleton
      remodeling.

PMID- 19168672
TI  - Epigenetic reprogramming and induced pluripotency.
AB  - The cloning of animals from adult cells has demonstrated that the developmental
      state of adult cells can be reprogrammed into that of embryonic cells by
      uncharacterized factors within the oocyte. More recently, transcription factors
      have been identified that can induce pluripotency in somatic cells without the
      use of oocytes, generating induced pluripotent stem (iPS) cells. iPS cells
      provide a unique platform to dissect the molecular mechanisms that underlie
      epigenetic reprogramming. Moreover, iPS cells can teach us about principles of
      normal development and disease, and might ultimately facilitate the treatment of
      patients by custom-tailored cell therapy.

PMID- 19168675
TI  - Notch mediates Wnt and BMP signals in the early separation of smooth muscle
      progenitors and blood/endothelial common progenitors.
AB  - During embryonic development in amniotes, the extraembryonic mesoderm, where the
      earliest hematopoiesis and vasculogenesis take place, also generates smooth
      muscle cells (SMCs). It is not well understood how the differentiation of SMCs is
      linked to that of blood (BCs) and endothelial (ECs) cells. Here we show that, in
      the chick embryo, the SMC lineage is marked by the expression of a bHLH
      transcription factor, dHand. Notch activity in nascent ventral mesoderm cells
      promotes SMC progenitor formation and mediates the separation of SMC and BC/EC
      common progenitors marked by another bHLH factor, Scl. This is achieved by
      crosstalk with the BMP and Wnt pathways, which are involved in mesoderm
      ventralization and SMC lineage induction, respectively. Our findings reveal a
      novel role of the Notch pathway in early ventral mesoderm differentiation, and
      suggest a stepwise separation among its three main lineages, first between SMC
      progenitors and BC/EC common progenitors, and then between BCs and ECs.

PMID- 19168674
TI  - Sall genes regulate region-specific morphogenesis in the mouse limb by modulating
      Hox activities.
AB  - The genetic mechanisms that regulate the complex morphogenesis of generating
      cartilage elements in correct positions with precise shapes during organogenesis,
      fundamental issues in developmental biology, are still not well understood. By
      focusing on the developing mouse limb, we confirm the importance of transcription
      factors encoded by the Sall gene family in proper limb morphogenesis, and further
      show that they have overlapping activities in regulating regional morphogenesis
      in the autopod. Sall1/Sall3 double null mutants exhibit a loss of digit1 as well
      as a loss or fusion of digit2 and digit3, metacarpals and carpals in the autopod.
      We show that Sall activity affects different pathways, including the Shh
      signaling pathway, as well as the Hox network. Shh signaling in the mesenchyme is
      partially impaired in the Sall mutant limbs. Additionally, our data suggest an
      antagonism between Sall1-Sall3 and Hoxa13-Hoxd13. We demonstrate that expression
      of Epha3 and Epha4 is downregulated in the Sall1/Sall3 double null mutants, and,
      conversely, is upregulated in Hoxa13 and Hoxd13 mutants. Moreover, the expression
      of Sall1 and Sall3 is upregulated in Hoxa13 and Hoxd13 mutants. Furthermore, by
      using DNA-binding assays, we show that Sall and Hox compete for a target sequence
      in the Epha4 upstream region. In conjunction with the Shh pathway, the
      antagonistic interaction between Hoxa13-Hoxd13 and Sall1-Sall3 in the developing
      limb may contribute to the fine-tuning of local Hox activity that leads to proper
      morphogenesis of each cartilage element of the vertebrate autopod.

PMID- 19168676
TI  - Formation of the bicoid morphogen gradient: an mRNA gradient dictates the protein
      gradient.
AB  - The Bicoid (Bcd) protein gradient is generally believed to be established in pre
      blastoderm Drosophila embryos by the diffusion of Bcd protein after translation
      of maternal mRNA, which serves as a strictly localized source of Bcd at the
      anterior pole. However, we previously published evidence that the Bcd gradient is
      preceded by a bcd mRNA gradient. Here, we have revisited and extended this
      observation by showing that the bcd mRNA and Bcd protein gradient profiles are
      virtually identical at all times. This confirms our previous conclusion that the
      Bcd gradient is produced by a bcd mRNA gradient rather than by diffusion. Based
      on our observation that bcd mRNA colocalizes with Staufen (Stau), we propose that
      the bcd mRNA gradient forms by a novel mechanism involving quasi-random active
      transport of a Stau-bcd mRNA complex through a nonpolar microtubular network,
      which confines the bcd mRNA to the cortex of the embryo.

PMID- 19168677
TI  - The polarly localized D6 PROTEIN KINASE is required for efficient auxin transport
      in Arabidopsis thaliana.
AB  - The phytohormone auxin is a major determinant of plant growth and
      differentiation. Directional auxin transport and auxin responses are required for
      proper embryogenesis, organ formation, vascular development, and tropisms.
      Members of several protein families, including the PIN auxin efflux facilitators,
      have been implicated in auxin transport; however, the regulation of auxin
      transport by signaling proteins remains largely unexplored. We have studied a
      family of four highly homologous AGC protein kinases, which we designated the D6
      protein kinases (D6PKs). We found that d6pk mutants have defects in lateral root
      initiation, root gravitropism, and shoot differentiation in axillary shoots, and
      that these phenotypes correlate with a reduction in auxin transport.
      Interestingly, D6PK localizes to the basal (lower) membrane of Arabidopsis root
      cells, where it colocalizes with PIN1, PIN2 and PIN4. D6PK and PIN1 interact
      genetically, and D6PK phosphorylates PIN proteins in vitro and in vivo. Taken
      together, our data show that D6PK is required for efficient auxin transport and
      suggest that PIN proteins are D6PK phosphorylation targets.

PMID- 19168678
TI  - Rostral and caudal pharyngeal arches share a common neural crest ground pattern.
AB  - In vertebrates, face and throat structures, such as jaw, hyoid and thyroid
      cartilages develop from a rostrocaudal metameric series of pharyngeal arches,
      colonized by cranial neural crest cells (NCCs). Colinear Hox gene expression
      patterns underlie arch specific morphologies, with the exception of the first
      (mandibular) arch, which is devoid of any Hox gene activity. We have previously
      shown that the first and second (hyoid) arches share a common, Hox-free,
      patterning program. However, whether or not more posterior pharyngeal arch neural
      crest derivatives are also patterned on the top of the same ground-state remained
      an unanswered question. Here, we show that the simultaneous inactivation of all
      Hoxa cluster genes in NCCs leads to multiple jaw and first arch-like structures,
      partially replacing second, third and fourth arch derivatives, suggesting that
      rostral and caudal arches share the same mandibular arch-like ground patterning
      program. The additional inactivation of the Hoxd cluster did not significantly
      enhance such a homeotic phenotype, thus indicating a preponderant role of Hoxa
      genes in patterning skeletogenic NCCs. Moreover, we found that Hoxa2 and Hoxa3
      act synergistically to pattern third and fourth arch derivatives. These results
      provide insights into how facial and throat structures are assembled during
      development, and have implications for the evolution of the pharyngeal region of
      the vertebrate head.

PMID- 19168679
TI  - Definitive hematopoietic stem/progenitor cells manifest distinct differentiation
      output in the zebrafish VDA and PBI.
AB  - One unique feature of vertebrate definitive hematopoiesis is the ontogenic
      switching of hematopoietic stem cells from one anatomical compartment or niche to
      another. In mice, hematopoietic stem cells are believed to originate in the aorta
      gonad-mesonephros (AGM), subsequently migrate to the fetal liver (FL) and finally
      colonize the bone marrow (BM). Yet, the differentiation potential of
      hematopoietic stem cells within early niches such as the AGM and FL remains
      incompletely defined. Here, we present in vivo analysis to delineate the
      differentiation potential of definitive hematopoietic stem/progenitor cells
      (HSPCs) in the zebrafish AGM and FL analogies, namely the ventral wall of dorsal
      aorta (VDA) and the posterior blood island (PBI), respectively. Cell fate mapping
      and analysis of zebrafish runx1(w84x) and vlad tepes (vlt(m651)) mutants revealed
      that HSPCs in the PBI gave rise to both erythroid and myeloid lineages. However,
      we surprisingly found that HSPCs in the VDA were not quiescent but were uniquely
      adapted to generate myeloid but not erythroid lineage cells. We further showed
      that such distinct differentiation output of HSPCs was, at least in part,
      ascribed to the different micro-environments present in these two niches. Our
      results highlight the importance of niche in shaping the differentiation output
      of developing HSPCs.

PMID- 19168680
TI  - Early mouse caudal development relies on crosstalk between retinoic acid, Shh and
      Fgf signalling pathways.
AB  - The progressive generation of embryonic trunk structures relies on the proper
      patterning of the caudal epiblast, which involves the integration of several
      signalling pathways. We have investigated the function of retinoic acid (RA)
      signalling during this process. We show that, in addition to posterior
      mesendoderm, primitive streak and node cells transiently express the RA
      synthesizing enzyme Raldh2 prior to the headfold stage. RA-responsive cells
      (detected by the RA-activated RARE-lacZ transgene) are additionally found in the
      epiblast layer. Analysis of RA-deficient Raldh2(-/-) mutants reveals early caudal
      patterning defects, with an expansion of primitive streak and mesodermal markers
      at the expense of markers of the prospective neuroepithelium. As a result, many
      genes involved in neurogenesis and/or patterning of the embryonic spinal cord are
      affected in their expression. We demonstrate that RA signalling is required at
      late gastrulation stages for mesodermal and neural progenitors to respond to the
      Shh signal. Whole-embryo culture experiments indicate that the proper response of
      cells to Shh requires two RA-dependent mechanisms: (1) a balanced antagonism
      between Fgf and RA signals, and (2) a RA-mediated repression of Gli2 expression.
      Thus, an interplay between RA, Fgf and Shh signalling is likely to be an
      important mechanism underpinning the tight regulation of caudal embryonic
      development.

PMID- 19168681
TI  - Actomyosin stiffens the vertebrate embryo during crucial stages of elongation and
      neural tube closure.
AB  - Physical forces drive the movement of tissues within the early embryo. Classical
      and modern approaches have been used to infer and, in rare cases, measure
      mechanical properties and the location and magnitude of forces within embryos.
      Elongation of the dorsal axis is a crucial event in early vertebrate development,
      yet the mechanics of dorsal tissues in driving embryonic elongation that later
      support neural tube closure and formation of the central nervous system is not
      known. Among vertebrates, amphibian embryos allow complex physical manipulation
      of embryonic tissues that are required to measure the mechanical properties of
      tissues. In this paper, we measure the stiffness of dorsal isolate explants of
      frog (Xenopus laevis) from gastrulation to neurulation and find dorsal tissues
      stiffen from less than 20 Pascal (Pa) to over 80 Pa. By iteratively removing
      tissues from these explants, we find paraxial somitic mesoderm is nearly twice as
      stiff as either the notochord or neural plate, and at least 10-fold stiffer than
      the endoderm. Stiffness measurements from explants with reduced fibronectin
      fibril assembly or disrupted actomyosin contractility suggest that it is the
      state of the actomyosin cell cortex rather than accumulating fibronectin that
      controls tissue stiffness in early amphibian embryos.

PMID- 19168683
TI  - Single specialty hospitals and nurse staffing patterns.
AB  - Advocates of physician-owned single specialty hospitals (SSHs) maintain that,
      through healthy competition, SSHs pressure competitor hospitals in local markets
      to improve performance. This paper investigates data trends on the effects of SSH
      entry on a potential indicator of quality of care in general hospital
      competitors: nurse staffing levels. We examined registered nurse (RN) staffing
      from 1997 to 2004 in ten states in which there was considerable SSH entry during
      this period. Regression estimates used longitudinal panel data models with
      hospital fixed effects to compare changes in numbers of RNs in general hospitals
      located in markets with SSHs with general hospitals located in markets where
      there were no SSHs. Results indicate that hospitals located in markets with
      orthopedic/surgical SSH presence raised their RN nurse staffing levels. Whether
      or not these changes are associated with improved patient outcomes is unknown.

PMID- 19168682
TI  - Dual sex-specific functions of Drosophila Upstream of N-ras in the control of X
      chromosome dosage compensation.
AB  - Dosage compensation in Drosophila melanogaster involves the assembly of the MSL-2
      containing dosage compensation complex (DCC) on the single X chromosome of male
      flies. Translational repression of msl-2 mRNA blocks this process in females.
      Previous work indicated that the ubiquitous protein Upstream of N-ras (UNR) is a
      necessary co-factor for msl-2 repression in vitro. Here, we explore the function
      of UNR in vivo. Hypomorphic Unr mutant flies showed DCC assembly on high-affinity
      sites in the female X chromosomes, confirming that UNR inhibits dosage
      compensation in female flies. Unexpectedly, male mutant flies and UNR-depleted
      SL2 cells showed decreased DCC binding to the X chromosome, suggesting a role for
      UNR in DCC assembly or targeting. Consistent with this possibility, UNR
      overexpression resulted in moderate loss of DCC from the male X chromosome and
      predominant male lethality. Immunoprecipitation experiments revealed that UNR
      binds to roX1 and roX2, the non-coding RNA components of the DCC, providing
      possible targets for UNR function in males. These results uncover dual sex
      specific functions of UNR in dosage compensation: to repress DCC formation in
      female flies and to promote DCC assembly on the male X chromosome.

PMID- 19168684
TI  - Case report. Lipomatous haemangiopericytoma (fat-forming solitary fibrous tumour)
      involving the perineum: CT and MRI findings and pathological correlation.
AB  - Lipomatous haemangiopericytoma (a fat-forming solitary fibrous tumour) is a rare
      soft-tissue tumour histologically characterized by haemangiopericytomatous
      vasculature and the presence of mature adipocytes. We report the CT and MRI
      findings of a case of lipomatous haemangiopericytoma involving the perineum. CT
      showed a well-circumscribed soft-tissue density mass containing a small area of
      fat density and a punctuate calcification. On MR images, the mass was mostly
      isointense to the muscle on T(1) weighted images, with heterogeneous signal
      intensity on T(2) weighted images, and showed strong contrast enhancement except
      for the fatty and dense collagenous components. This is the first case report of
      imaging findings of a lipomatous haemangiopericytoma in the radiological
      literature. Although rare, lipomatous haemangiopericytoma should be considered as
      a differential diagnosis of fat-containing, hypervascular soft-tissue tumours
      with variable signal intensity on T(2) weighted images.

PMID- 19168685
TI  - Case report. An unusual thoracic mass.
AB  - Intrathoracic renal ectopia is a rare congenital abnormality that is often
      discovered incidentally. Plain radiography of the chest is often indeterminate,
      particularly in cases where there may be more than one pathology. CT is the
      mainstay of diagnosis in such cases where malignant or benign features may be
      identified and, as in this case report, it can confirm confidently the diagnosis
      of a rare benign mass and negate the need for further investigation. Here, the
      clinical and radiological findings of intrathoracic kidneys are discussed,
      together with a review of the literature.

PMID- 19168686
TI  - Case report. Non-secretory multiple myeloma presenting with diffuse sclerosis of
      affected bones interspersed with osteolytic lesions.
AB  - Non-secretory multiple myeloma (NSMM) is a rare variant of the classic form of
      multiple myeloma in which no monoclonal gammopathy can be demonstrated in the
      serum or urine. Most reported cases of NSMM show the presence of lytic lesions on
      skeletal radiography. We describe a rare case of non-secretory myeloma in a 32
      year-old Indian woman. No monoclonal gammopathy was found in the serum or urine,
      but a skeletal survey showed diffuse osteosclerosis interspersed with osteolytic
      lesions; bone marrow biopsy revealed marked plasmacytosis. As diffuse
      osteosclerosis has never been reported in NSMM, we felt that this was a case
      worthy of report.

PMID- 19168687
TI  - Case report. Duplication of the portal vein: a rare congenital anomaly.
AB  - Complex developmental changes occur during embryonic life as the vitelline veins
      evolve into the portal vein. Duplication of the portal vein is an uncommon
      anomaly. Complications of this anomaly include variceal bleeding, portal
      hypertension and duodenal obstruction. We report a case of this uncommon anomaly
      and present an embryological perspective as to the cause for this abnormal
      configuration of the portal veins.

PMID- 19168688
TI  - Case report. Appearance of nephrogenic fibrosing dermopathy on a bone scan.
AB  - We report a case of nephrogenic systemic fibrosis involving the thighs
      bilaterally in a patient who received multiple MRI scans with gadolinium. A
      recent bone scan demonstrated uptake of radiotracer in a region that correlates
      with CT and dermatopathological findings.

PMID- 19168689
TI  - Case report. Isolated left ventricular myocardium non-compaction: MR imaging
      findings from three cases.
AB  - The purpose of this study is to report three cases of left ventricular myocardium
      non-compaction (LVNC), with emphasis on the MRI findings. From May 2006 to
      February 2007, three patients -- 2 females (6 years and 42 years of age) and 1
      male (18 years of age) -- presented to our radiology department, two of them with
      fatigue, shortness of breath and episodes of syncope and arrhythmia, for further
      investigation by cardiac MRI because an apparent asymmetrical pattern of
      hypertrophy of the left ventricular myocardium was suspected by transthoracic
      echocardiography. The 18-year-old patient was only experiencing arrhythmia, and
      arrhythmogenic right ventricular dysplasia was suspected. The images (produced by
      a 1.5T MRI system) were interpreted by two experienced radiologists and post
      processed with Argus software (Siemens, Germany) for ejection fraction
      calculation. In all three patients, MRI aided in the correct identification of
      prominent ventricular myocardial trabeculations and deep intertrabecular recesses
      communicating with the ventricular cavity, as well as areas of hypokinesia with
      depressed systolic function, and showed the absence of myocardial delayed
      enhancement and other structural heart defects. In conclusion, cardiac MRI was
      useful for correctly identifying this rare congenital heart disorder and appears
      to increase diagnostic accuracy. Although considered a rare anomaly, radiologists
      should be capable of recognizing LVNC, as current non-invasive imaging methods
      have increased the frequency of this diagnosis and timely detection is vital in
      considering early-stage transplantation.

PMID- 19168690
TI  - The importance of radiation chemistry to radiation and free radical biology (The
      2008 Silvanus Thompson Memorial Lecture).
AB  - Biological effects of radiation are manifest over timescales extending to years.
      However, many chemical events are complete in milliseconds; after this time,
      adding oxygen to irradiated hypoxic cells no longer enhances radiosensitivity.
      This does not mean that damage pathways cannot be modified; the potential gain
      from chemical modulation of early events is as large as any associated with later
      pathways, and the prognostic importance of variations in levels of small
      molecules active in fast free radical pathways is as important as any associated
      with genetic make-up. Reactive oxygen species are much invoked in the wider
      context, but are frequently undefined and seldom measured unambiguously.
      Radiation chemistry has much to offer to both radiation and free radical biology.
      An appreciation of the interlinked parameters of time, spatial distribution and
      yield is well developed, as are methods to generate specific radicals in known
      concentrations and to monitor their reactions directly. Intense clinical interest
      in the 1980s in hypoxic cell radiosensitizers, developed from radiation chemical
      studies, has waned, but the goal of eliminating hypoxic radioresistance remains
      attractive. Nitric oxide may be more important than oxygen in determining hypoxic
      radiosensitivity, and radiation chemistry provides the tools to understand the
      mechanisms and the limitations of in vitro models. Imaging hypoxia in tumours
      relies heavily on free radical chemistry and radiolysis methods to understand the
      mechanistic basis for diagnostic agents. Quantitation of the chemical reactivity
      of free radicals is a cornerstone of radiation chemistry via the language,
      concepts and mathematics of chemical kinetics, which are equally applicable to
      understanding the molecular pathways in radiobiology.

PMID- 19168691
TI  - Whole-body adipose tissue analysis: comparison of MRI, CT and dual energy X-ray
      absorptiometry.
AB  - The aim of this study was to validate a recently proposed MRI-based T(1)-mapping
      method for analysis of whole-body adipose tissue (AT) using an established CT
      protocol as reference and to include results from dual energy X-ray
      absorptiometry (DEXA). 10 subjects, drawn from the Swedish Obese Subjects Sibling
      pairs study, were examined using CT, MRI and DEXA. The CT analysis was based on
      28 imaged slices. T(1) maps were calculated using contiguous MRI data from two
      different gradient echo sequences acquired using different flip angles. CT and
      MRI comparison was performed slice-wise and for the whole-body region. Fat
      weights were compared between all three modalities. Strong correlations (r > or =
      0.977, p<0.0001) were found between MRI and CT whole-body and AT volumes. MRI
      visceral AT volume was underestimated by 0.79 +/- 0.75 l (p = 0.005), but total
      AT was not significantly different from that estimated by CT (MRI - CT = -0.61+/
      1.17 l; p = 0.114). DEXA underestimated fat weights by 5.23 +/- 1.71 kg (p =
      0.005) compared with CT. MRI underestimated whole-body volume by 2.03 +/- 1.61 l
      (p = 0.005) compared with CT. Weights estimated either by CT or by DEXA were not
      significantly different from weights measured using scales. In conclusion, strong
      correlations were found between whole-body AT results from CT, MRI-based T(1)
      mapping and DEXA. If the differences between the results from T(1)-mapping and CT
      based analysis are accepted, the T(1)-mapping method allows fully automated post
      processing of whole-body MRI data, allowing longitudinal whole-body studies that
      are also applicable for children and adolescents.

PMID- 19168692
TI  - Dynamic contrast-enhanced MRI for prostate cancer localization.
AB  - Radiotherapy dose escalation improves tumour control in prostate cancer but with
      increased toxicity. Boosting focal tumour only may allow dose escalation with
      acceptable toxicity. Intensity-modulated radiotherapy can deliver this, but
      visualization of the tumour remains limiting. CT or conventional MRI techniques
      are poor at localizing tumour, but dynamic contrast-enhanced MRI (DCE-MRI) may be
      superior. 18 patients with prostate cancer had T(2) weighted (T2W) and DCE-MRI
      prior to prostatectomy. The prostate was sectioned meticulously so as to achieve
      accurate correlation between imaging and pathology. The accuracy of DCE-MRI for
      cancer detection was calculated by a pixel-by-pixel correlation of quantitative
      DCE-MRI parameter maps and pathology. In addition, a radiologist interpreted the
      DCE-MRI and T2W images. The location of tumour on imaging was compared with
      histology, and the accuracy of DCE-MRI and T2W images was then compared. Pixel-by
      pixel comparison of quantitative parameter maps showed a significant difference
      between the benign peripheral zone and tumour for the parameters K(trans), v(e)
      and k(ep). Calculation of areas under the receiver operating characteristic curve
      showed that the pharmacokinetic parameters were only "fair" discriminators
      between cancer and benign gland. Interpretation of DCE-MRI and T2W images by a
      radiologist showed DCE-MRI to be more sensitive than T2W images for tumour
      localization (50% vs 21%; p = 0.006) and similarly specific (85% vs 81%; p =
      0.593). The superior sensitivity of DCE-MRI compared with T2W images, together
      with its high specificity, is arguably sufficient for its use in guiding
      radiotherapy boosts in prostate cancer.

PMID- 19168693
TI  - Dementia spectroscopy and diagnostic yield.

PMID- 19168694
TI  - Case of the month. Double vision. Differentials please!

PMID- 19168695
TI  - MRI assessment of hemodynamic effects of angiopoietin-2 overexpression in a brain
      tumor model.
AB  - Despite treatment efforts, the median survival in patients with glioblastoma
      multiforme, the most aggressive form of glioma, does not extend beyond 12-15
      months. One of the major pathophysiological characteristics of these tumors is
      their ability to induce active angiogenesis. Thus, based on the lack of efficient
      therapies, agents that inhibit angiogenesis are particularly attractive as a
      therapeutic option. However, it has been recently proposed that although
      specifically targeting vascular endothelial growth factor, the main angiogenic
      factor, certainly leads to significant tumor regression, it could also be
      followed by tumor relapses. In this case, angiogenesis is driven by alternate
      pathways that include other angiogenic factors. One possible strategy to overcome
      this therapeutic obstacle is to overexpress antivascular factors such as
      angiopoietin-2 (Ang2). Here, by using MRI and histological analysis, we studied
      the vascular events involved in glioma growth impairment induced by Ang2
      overexpression. Our results show that an increase in Ang2 expression, during the
      tumor growth, leads to a significant decrease in tumor growth ( approximately
      86%) along with an increase in the survival median ( approximately 70%) but does
      not modify the tumor vascular area or cerebral blood volume. However, tumor Ang2
      derived blood vessels display an abnormal, enlarged morphology. We show that the
      presence of Ang2 leads to an enhancement of tumor perfusion and a decrease in
      tumor vessel permeability. Based on our MR image evaluations of hemodynamic tumor
      vessel changes, we propose that Ang2-derived tumor vessels lead to an inadequate
      oxygenation of the tumor tissue, leading to impairment in tumor growth.

PMID- 19168696
TI  - Transforming growth factor-beta enhances rhinovirus infection by diminishing
      early innate responses.
AB  - Individuals with asthma are prone to viral and bacterial infections, and most
      asthma exacerbations have been linked to viruses, particularly rhinovirus. Excess
      transforming growth factor (TGF)-beta present in asthmatic airways may cause
      immune suppression, as well as transdifferentiate fibroblasts to myofibroblasts,
      thereby augmenting proinflammatory responses after rhinovirus infection. After
      rhinovirus infection we examined virus replication and host cell immune responses
      in airway fibroblasts in the presence of TGF-beta1 and in myofibroblasts. Primary
      culture fibroblasts were pretreated with TGF-beta1 or transdifferentiated into
      myofibroblasts, and then infected with rhinovirus. Viral replication, virus
      release, chemokine production, and interferon (IFN) responses were measured over
      72 hours. Rhinovirus replication and virus release into supernatants were
      enhanced in fibroblasts incubated with TGF-beta1 and in fibroblasts obtained from
      patients with asthma. Myofibroblasts also showed more rhinovirus replication, and
      infected myofibroblasts produced excess neutrophil chemokines. Examination of
      innate responses revealed blunting of type I IFN reactions with dissociated viral
      RNA and IFN mRNA responses. Addition of type I IFN restituted antiviral
      responses, and the effect of TGF-beta1 appeared to be mediated via actions on IFN
      regulatory factor-3 pathways. These data demonstrate that TGF-beta1 mediates
      enhanced virus replication and proinflammatory responses in airway cells. TGF
      beta may act as an endogenous immunosuppressant promoting virus replication and
      inflammation during the evolution of acute severe asthma associated with
      rhinovirus infection.

PMID- 19168697
TI  - Adiponectin deficiency increases allergic airway inflammation and pulmonary
      vascular remodeling.
AB  - Obesity is associated with an increased incidence and severity of asthma, as well
      as other lung disorders, such as pulmonary hypertension. Adiponectin (APN), an
      antiinflammatory adipocytokine, circulates at lower levels in the obese, which is
      thought to contribute to obesity-related inflammatory diseases. We sought to
      determine the effects of APN deficiency in a murine model of chronic asthma.
      Allergic airway inflammation was induced in APN-deficient mice (APN(-/-)) using
      sensitization without adjuvant followed by airway challenge with ovalbumin. The
      mice were then analyzed for changes in inflammation and lung remodeling. APN(-/-)
      mice in this model develop increased allergic airway inflammation compared with
      wild-type mice, with greater accumulation of eosinophils and monocytes in the
      airways associated with elevated lung chemokine levels. Surprisingly, APN(-/-)
      mice developed severe pulmonary arterial muscularization and pulmonary arterial
      hypertension in this model, whereas wild-type mice had only mild vascular
      remodeling and comparatively less pulmonary arterial hypertension. Our findings
      demonstrate that APN modulates allergic inflammation and pulmonary vascular
      remodeling in a model of chronic asthma. These data provide a possible mechanism
      for the association between obesity and asthma, and suggest a potential novel
      link between obesity, inflammatory lung disease, and pulmonary hypertension.

PMID- 19168698
TI  - Mitochondrial dysfunction contributes to alveolar developmental arrest in
      hyperoxia-exposed mice.
AB  - This study investigated whether mitochondrial dysfunction contributes to alveolar
      developmental arrest in a mouse model of bronchopulmonary dysplasia (BPD). To
      induce BPD, 3-day-old mice were exposed to 75% O2. Mice were studied at two time
      points of hyperoxia (72 h or 2 wk) and after 3 weeks of recovery in room air
      (RA). A separate cohort of mice was exposed to pyridaben, a complex-I (C-I)
      inhibitor, for 72 hours or 2 weeks. Alveolarization was quantified by radial
      alveolar count and mean linear intercept methods. Pulmonary mitochondrial
      function was defined by respiration rates, ATP-production rate, and C-I activity.
      At 72 hours, hyperoxic mice demonstrated significant inhibition of C-I activity,
      reduced respiration and ATP production rates, and significantly decreased radial
      alveolar count compared with controls. Exposure to pyridaben for 72 hours, as
      expected, caused significant inhibition of C-I and ADP-phosphorylating
      respiration. Similar to hyperoxic littermates, these pyridaben-exposed mice
      exhibited significantly delayed alveolarization compared with controls. At 2
      weeks of exposure to hyperoxia or pyridaben, mitochondrial respiration was
      inhibited and associated with alveolar developmental arrest. However, after 3
      weeks of recovery from hyperoxia or 2 weeks after 72 hours of exposure to
      pyridaben alveolarization significantly improved. In addition, there was marked
      normalization of C-I and mitochondrial respiration. The degree of hyperoxia
      induced pulmonary simplification and recovery strongly (r(2) = 0.76) correlated
      with C-I activity in lung mitochondria. Thus, the arrest of alveolar development
      induced by either hyperoxia or direct inhibition of mitochondrial oxidative
      phosphorylation indicates that bioenergetic failure to maintain normal alveolar
      development is one of the fundamental mechanisms responsible for BPD.

PMID- 19168699
TI  - IL-6 protects against hyperoxia-induced mitochondrial damage via Bcl-2-induced
      Bak interactions with mitofusins.
AB  - Overexpression of IL-6 markedly diminishes hyperoxic lung injury, hyperoxia
      induced cell death, and DNA fragmentation, and enhances Bcl-2 expression. We
      hypothesized that changes in the interactions between Bcl-2 family members play
      an important role in the IL-6-mediated protective response to oxidative stress.
      Consistent with this hypothesis, we found that IL-6 induced Bcl-2 expression,
      both in vivo and in vitro, disrupted interactions between proapoptotic and
      antiapoptotic factors, and suppressed H(2)O(2)-induced loss of mitochondrial
      membrane potential in vitro. In addition, IL-6 overexpression in mice protects
      against hyperoxia-induced lung mitochondrial damage. The overexpression of Bcl-2
      in vivo prolonged the survival of mice exposed to hyperoxia and inhibited
      alveolar capillary protein leakage. In addition, apoptosis-associated DNA
      fragmentation was substantially reduced in these animals. This IL-6-mediated
      protection was lost when Bcl-2 was silenced, demonstrating that Bcl-2 is an
      essential mediator of IL-6 cytoprotection. Finally, Bcl-2 blocked the
      dissociation of Bak from mitofusin protein (Mfn) 2, and inhibited the interaction
      between Bak and Mfn1. Taken together, our results suggest that IL-6 induces Bcl-2
      expression to perform cytoprotective functions in response to oxygen toxicity,
      and that this effect is mediated by alterations in the interactions between Bak
      and Mfns.

PMID- 19168700
TI  - Tobramycin and FDA-approved iron chelators eliminate Pseudomonas aeruginosa
      biofilms on cystic fibrosis cells.
AB  - The ability of Pseudomonas aeruginosa to form antibiotic-resistant biofilms is
      thought to account for the inability of current therapies to resolve bacterial
      infections in the lungs of patients with cystic fibrosis (CF). We recently
      described a system in which highly antibiotic-resistant P. aeruginosa biofilms
      grow on human CF airway epithelial cells, and using this system we showed that
      enhanced iron release from CF cells facilitates the development of such highly
      antibiotic-resistant biofilms. Given the positive role for iron in biofilm
      development, we investigated whether the FDA-approved iron chelators deferoxamine
      and deferasirox would enhance the ability of tobramycin, the primary antibiotic
      used to treat CF lung infections, to eliminate P. aeruginosa biofilms. The
      combination of tobramycin with deferoxamine or deferasirox reduced established
      biofilm biomass by approximately 90% and reduced viable bacteria by 7-log units.
      Neither tobramycin nor deferoxamine nor deferasirox alone had such a marked
      effect. The combination of tobramycin and FDA-approved iron chelators also
      prevented the formation of biofilms on CF airway cells. These data suggest that
      the combined use of tobramycin and FDA-approved iron chelators may be an
      effective therapy to treat patients with CF and other lung disease characterized
      by antibiotic-resistant P. aeruginosa biofilms.

PMID- 19168701
TI  - Defective acid sphingomyelinase pathway with Pseudomonas aeruginosa infection in
      cystic fibrosis.
AB  - Acid sphingomyelinase (ASMase) is a key enzyme in sphingolipid metabolism, which
      can be activated by various cellular stress mechanisms including bacterial
      pathogens. Activation of ASMase generates ceramide, which is important for innate
      immune response to eliminate infected pathogens. The current study reveals a
      defective ASMase pathway after Pseudomonas aeruginosa infection in both a cystic
      fibrosis (CF) bronchial epithelial cell line (IB3-1 cell) and in the lungs of CF
      transmembrane conductance regulator (CFTR) knockout (KO) mice as compared with S9
      cells and wild-type C57BL/6 mice. ASMase activity and total ceramide levels
      significantly increased in S9 cells and C57BL/6 mice with P. aeruginosa
      infection, but not in IB3-1 cells and CFTR KO mice. The silencing of CFTR by CFTR
      RNAi in S9 cells significantly decreased ASMase activity after bacterial
      infection as compared with controls. This study also demonstrates that induction
      of ASMase is responsible for modulating the immune response to bacterial
      infection. Blocking ASMase activity with specific ASMase RNAi, an ASMase
      inhibitor, or an ASMase antibody in S9 cells significantly increased IL-8 levels
      with P. aeruginosa infection compared with controls. Reciprocally, adding
      exogenous bacterial sphingomyelinase to IB3-1 cells significantly decreased IL-8
      levels compared with untreated cells. In addition, silencing of ASMase in S9
      cells also significantly decreased bacterial internalization. Adding exogenous
      bacterial sphingomyelinase to IB3-1 cells reconstituted the cell death response
      to P. aeruginosa infection. This study demonstrates that the defective ASMase
      pathway in CF is a key contributor to the unabated IL-8 response with P.
      aeruginosa infection and to the compromised host response failing to eradicate
      bacteria.

PMID- 19168702
TI  - CFTR regulation of intracellular pH and ceramides is required for lung
      endothelial cell apoptosis.
AB  - The functional significance of the expression of cystic fibrosis transmembrane
      regulator (CFTR) on endothelial cells has not yet been elucidated. Since CFTR has
      been implicated in the regulation of intracellular sphingolipid levels, which are
      important regulators of endothelial cell apoptosis in response to various
      insults, we investigated the role of CFTR in the apoptotic responses of lung
      endothelial cells. CFTR was detected as a functional chloride channel in primary
      lung endothelial cells isolated from both pulmonary arteries (human or mouse) and
      bronchial arteries (sheep). Both specific CFTR inhibition with 2-(phenylamino)
      benzoic acid diphenylamine-2-carboxylic acid, 5-[(4-carboxyphenyl)methylene]-2
      thioxo-3-[(3-trifluoromethyl)phenyl-4-thiazolidinone (CFTR(inh)-172), or 5-nitro
      2-(3-phenylpropylamino)benzoic acid and CFTR knockdown significantly attenuated
      endothelial cell apoptosis induced by staurosporine or H(2)O(2). CFTR(inh)-172
      treatment prevented the increases in the ceramide:sphingosine-1 phosphate ratio
      induced by H(2)O(2) in lung endothelial cells. Replenishing endogenous ceramides
      via sphingomyelinase supplementation restored the susceptibility of CFTR
      inhibited lung endothelial cells to H(2)O(2)-induced apoptosis. Similarly, the
      anti-apoptotic phenotype of CFTR-inhibited cells was reversed by lowering the
      intracellular pH, and was reproduced by alkalinization before H(2)O(2) challenge.
      TUNEL staining and active caspase-3 immunohistochemistry indicated that cellular
      apoptosis was decreased in lung explants from patients with cystic fibrosis
      compared with those with smoking-induced chronic obstructive lung disease,
      especially in the alveolar tissue and vascular endothelium. In conclusion, CFTR
      function is required for stress-induced apoptosis in lung endothelial cells by
      maintaining adequate intracellular acidification and ceramide activation. These
      results may have implications in the pathogenesis of cystic fibrosis, where
      aberrant endothelial cell death may dysregulate lung vascular homeostasis,
      contributing to abnormal angiogenesis and chronic inflammation.

PMID- 19168703
TI  - Chronic intermittent mechanical stress increases MUC5AC protein expression.
AB  - Increased abundance of mucin secretory cells is a characteristic feature of the
      epithelium in asthma and other chronic airway diseases. We showed previously that
      the mechanical stresses of airway constriction, both in the intact mouse lung and
      a cell culture model, activate the epidermal growth factor receptor (EGFR), a
      known modulator of mucin expression in airway epithelial cells. Here we tested
      whether chronic, intermittent, short-duration compressive stress (30 cm H(2)O) is
      sufficient to increase the abundance of MUC5AC-positive cells and intracellular
      mucin levels in human bronchial epithelial cells cultured at an air-liquid
      interface. Compressive stress applied for 1 hour per day for 14 days
      significantly increased the percentage of cells staining positively for MUC5AC
      protein (22.0 +/- 3.8%, mean +/- SD) relative to unstimulated controls (8.6 +/-
      2.6%), and similarly changed intracellular MUC5AC protein levels measured by
      Western and slot blotting. The effect of compressive stress was gradual, with
      significant changes in MUC5AC-positive cell numbers evident by Day 7, but
      required as little as 10 minutes of compressive stress daily. Daily treatment of
      cells with an EGFR kinase inhibitor (AG1478, 1 muM) significantly but
      incompletely attenuated the response to compressive stress. Complete attenuation
      could be accomplished by simultaneous treatment with the combination of AG1478
      and a transforming growth factor (TGF)-beta(2) (1 microg/ml)-neutralizing
      antibody, or with anti-TGF-beta(2) alone. Our findings demonstrate that short
      duration episodes of mechanical stress, representative of those occurring during
      bronchoconstriction, are sufficient to increase goblet cell number and MUC5AC
      protein expression in bronchial epithelial cells in vitro. We propose that the
      mechanical environment present in asthma may fundamentally bias the composition
      of airway epithelial lining in favor of mucin secretory cells.

PMID- 19168704
TI  - Generation of transplantable, functional satellite-like cells from mouse
      embryonic stem cells.
AB  - Satellite cells are myogenic stem cells responsible for the postnatal
      regeneration of skeletal muscle. Here we report the successful in vitro induction
      of Pax7-positive satellite-like cells from mouse embryonic stem (mES) cells.
      Embryoid bodies were generated from mES cells and cultured on Matrigel-coated
      dishes with Dulbecco's modified Eagle medium containing fetal bovine serum and
      horse serum. Pax7-positive satellite-like cells were enriched by fluorescence
      activated cell sorting using a novel anti-satellite cell antibody, SM/C-2.6. SM/C
      2.6-positive cells efficiently differentiate into skeletal muscle fibers both in
      vitro and in vivo. Furthermore, the cells demonstrate satellite cell
      characteristics such as extensive self-renewal capacity in subsequent muscle
      injury model, long-term engraftment up to 24 wk, and the ability to be
      secondarily transplanted with remarkably high engraftment efficiency compared to
      myoblast transplantation. This is the first report of transplantable, functional
      satellite-like cells derived from mES cells and will provide a foundation for new
      therapies for degenerative muscle disorders.

PMID- 19168705
TI  - Epithelial phosphatase and tensin homolog regulates intestinal architecture and
      secretory cell commitment and acts as a modifier gene in neoplasia.
AB  - Phosphatase and tensin homolog (PTEN), a negative regulator of the
      phosphatidylinositol 3-kinase/Akt pathway, is one of the most frequently
      mutated/deleted tumor suppressor genes in human cancers. The aim of this study
      was to gain insight into the role played by PTEN in intestinal homeostasis and
      epithelial cell function. Using the Cre/loxP system, we have generated a mouse
      with a conditional intestinal epithelial Pten deficiency. Pten mutant mice and
      controls were sacrificed for histology, immunofluorescence, Western blot, and
      quantitative polymerase chain reaction analysis. Our results show that loss of
      epithelial Pten leads to an intestinalomegaly associated with an increase in
      epithelial cell proliferation. Histological analysis demonstrated significant
      perturbation of the crypt-villus architecture, a marked increase in goblet cells
      and a decrease in enteroendocrine cells, suggesting a role for Pten in the
      commitment of the multipotential-secretory precursor cell. Loss of epithelial
      Pten does not result in induction of nuclear beta-catenin protein levels, nor is
      it sufficient to promote tumorigenesis initiation. However, it severely enhances
      intestinal tumor load in Apc(Min/+) mice, in which c-Myc is already deregulated.
      These results reveal an unknown function for Pten signaling in the commitment of
      multipotential-secretory progenitor cells and suggest that epithelial Pten
      functions as a modifier gene in intestinal neoplasia.

PMID- 19168706
TI  - T-cell receptor signaling is mediated by transient Lck activity, which is
      inhibited by inorganic mercury.
AB  - Genetically susceptible rodents exposed to low nontoxic levels of inorganic
      mercury (Hg(2+)) develop idiosyncratic autoimmune disease associated with
      defective T-cell function. However, the molecular mechanisms underlying this
      phenomenon remain mostly unexplained. Brief exposure of T cells to micromolar
      concentrations of Hg(2+) leads to physiologically relevant nontoxic cellular
      mercury burdens, and as we have previously reported, attenuates T-cell receptor
      (TCR) signal strength by approximately 50%. We have found this to be the result
      of an inadequate activation of the tyrosine kinase ZAP-70, which is
      hypophosphorylated following TCR stimulation in Hg(2+) burdened cells when
      compared to untreated controls. In T cells, ZAP-70 phosphorylation is dependent
      on lymphocyte-specific protein tyrosine kinase (Lck) activity, which in turn is
      either positively or negatively regulated by the phosphorylation of specific Lck
      tyrosine residues. In particular, the general belief is that Lck is negatively
      regulated by phosphorylation of tyrosine 192 (Y192). We now demonstrate by
      Western blotting that, in Jurkat T cells, TCR signal transduction (and ZAP-70
      phosphorylation) was positively associated with a rapid transient phosphorylation
      of Y192, which was inhibited in cells that were briefly (5 min) exposed to 5
      microM Hg(2+). Thus, Hg(2+) inhibits a critical activating role played by Lck
      Y192 during the most proximal events of the TCR-induced cell signaling.

PMID- 19168707
TI  - Endocannabinoid modulation of scratching response in an acute allergenic model: a
      new prospective neural therapeutic target for pruritus.
AB  - Pruritus (itch) is a common cause of discomfort by dermatological disorders.
      Several peripherally and centrally mediated pathologies that induce pruritus do
      not generally respond to typical allergenic and anti-inflammatory treatments. In
      accordance, we employed an acute allergenic murine model to determine whether the
      endogenous cannabinoid system could be targeted to treat pruritus. Subcutaneous
      administration of the mast cell degranulator compound 48/80 evoked an intense,
      concentration-dependent scratching response. Systemic Delta(9)
      tetrahydrocannabinol reduced the scratching response, although this effect was
      accompanied with hypomotility. Complementary genetic and pharmacological
      approaches to target fatty acid amide hydrolase (FAAH), the primary enzyme
      responsible for the degradation of the endocannabinoid anandamide, were evaluated
      in the compound 48/80 model. FAAH(-/-) mice and mice treated with the respective
      irreversible and reversible FAAH inhibitors, URB597 (cyclohexylcarbamic acid 3'
      carbamoylbiphenyl-3-yl ester) and OL-135 [1-oxo-1-[5-(2-pyridyl)-2-yl]-7
      phenylheptane], displayed comparable reductions in scratching to mice treated
      with common nonsedative allergenic treatments (loratadine and dexamethasone) but
      without affecting locomotor behavior. The antiscratching phenotype of FAAH
      compromised mice was completely blocked by either genetic deletion or
      pharmacological antagonism of the CB(1) receptor. Neural-specific conditional
      FAAH knockout (FAAH-NS) mice, which have FAAH exclusively restricted to neural
      tissues, showed a similar magnitude of scratching as wild-type mice. It is
      important that URB597 reduced compound 48/80-induced scratching in FAAH-NS mice,
      but it did not produce any further reduction in FAAH(-/-) mice. These findings
      indicate that neuronal FAAH suppression reduces the scratching response through
      activation of CB(1) receptors. More generally, these are the first preclinical
      data suggesting that FAAH represents a novel target to treat pruritus without
      eliciting overt side effects.

PMID- 19168708
TI  - Rewarding morphine-induced synaptic function of delta-opioid receptors on central
      glutamate synapses.
AB  - The rewarding effect of opioids, the driving force for compulsive behaviors of
      opioid abuse and addiction, is primarily mediated by the mu-opioid receptor.
      However, the role of the delta-opioid receptor (DOR) in opioid reward and
      addiction is still poorly understood. The recently discovered adaptive DOR
      property of exocytotic translocation in sensory neurons after chronic opioid
      exposure provides a new avenue of conceptual thoughts to exploring the DOR
      function in this psychoneurological disease. In this study, we investigated
      potential adaptive function of DOR in neurons of the central nucleus of the
      amygdala (CeA), a forebrain structure increasingly recognized for mediating
      stimulus reward learning in drug addiction. Using whole-cell recordings in CeA
      slices, we found that in rats displaying morphine-induced behavior of conditioned
      place preference, a behavioral measure of drug reward, the overall synaptic
      strength of glutamate synapses in CeA neurons was significantly enhanced. The
      selective DOR agonist [D-Pen(2),D-Pen(5)]-enkephalin, having no apparent effect
      on glutamatergic excitatory postsynaptic current (EPSC) in neurons from control
      rats, produced a significant, dose-dependent inhibition of the synaptic current
      in neurons from those morphine-treated rats. Detailed analyses of EPSC properties
      revealed that DOR activation inhibited the EPSC by reducing presynaptic release
      of glutamate, indicating functional DOR emerging on presynaptic glutamate
      terminals. The morphine treatment also significantly increased DOR proteins in
      CeA preparations of synaptosomes. These findings provide functional evidence for
      an adaptive modulation by presynaptic DOR of a key synaptic activity altered by
      morphine, thus implying likely important involvement of DOR in opioid reward and
      addiction.

PMID- 19168709
TI  - Metabolic activation of mifepristone [RU486; 17beta-hydroxy-11beta-(4
      dimethylaminophenyl)-17alpha-(1-propynyl)-estra-4,9-dien-3-one] by mammalian
      cytochromes P450 and the mechanism-based inactivation of human CYP2B6.
AB  - Mifepristone [RU486; 17beta-hydroxy-11beta-(4-dimethylaminophenyl)-17alpha-(1
      propynyl)-estra-4,9-dien-3-one] inactivates CYP2B6 in the reconstituted system in
      a mechanism-based manner. The loss of 7-ethoxy-4-(trifluoromethyl)-coumarin
      deethylation activity of CYP2B6 is concentration- and time-dependent. The
      inactivation requires NADPH and is irreversible. The concentration of inactivator
      required to give the half-maximal rate of inactivation is 2.8 microM, and the
      maximal rate constant for inactivation at a saturating concentration of the
      inactivator is 0.07 min(-1). Incubation of CYP2B6 with 20 microM RU486 for 15 min
      resulted in 61% loss of catalytic activity, 60% loss of the reduced cytochrome
      P450 (P450)-CO complex, and a 40% loss of native heme. The partition ratio is
      approximately 5, and the stoichiometry of binding is approximately 0.6 mol
      RU486/mol P450 inactivated. SDS-polyacrylamide gel electrophoresis and high
      pressure liquid chromatography analysis showed that [(3)H]RU486 was irreversibly
      bound to CYP2B6 apoprotein. RU486 is metabolized to form three major metabolites
      and bioactivated to give reactive intermediates by purified P450s in the
      reconstituted system. After incubation of RU486 with the purified P450s and liver
      microsomes from rats and humans in the presence of glutathione (GSH) and NADPH,
      GSH conjugates with MH(+) ions at m/z 769, 753, and 751 were detected by liquid
      chromatography-tandem mass spectrometry. Two GSH conjugates with MH(+) ions at
      m/z 753 are formed from the reaction of GSH with RU486. The adducts are formed
      after addition of an activated oxygen to the carbon-carbon triple bond of the
      propynyl moiety. This suggests that oxirene intermediates may be involved in the
      mechanism of inactivation. It seems that the potential for drug-drug interactions
      of RU486 may not be limited only to CYP3A4 and should also be evaluated for drugs
      metabolized primarily by CYP2B6, such as bupropion and efavirenz.

PMID- 19168710
TI  - A novel, highly selective, tight binding IkappaB kinase-2 (IKK-2) inhibitor: a
      tool to correlate IKK-2 activity to the fate and functions of the components of
      the nuclear factor-kappaB pathway in arthritis-relevant cells and animal models.
AB  - Nuclear factor (NF)-kappaB activation has been clearly linked to the pathogenesis
      of multiple inflammatory diseases including arthritis. The central role that
      IkappaB kinase-2 (IKK-2) plays in regulating NF-kappaB signaling in response to
      inflammatory stimuli has made this enzyme an attractive target for therapeutic
      intervention. Although diverse chemical classes of IKK-2 inhibitors have been
      identified, the binding kinetics of these inhibitors has limited the scope of
      their applications. In addition, safety assessments of IKK-2 inhibitors based on
      a comprehensive understanding of the pharmacokinetic/pharmacodynamic
      relationships have yet to be reported. Here, we describe a novel, potent, and
      highly selective IKK-2 inhibitor, PHA-408 [8-(5-chloro-2-(4-methylpiperazin-1
      yl)isonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo[g]indazole-3
      carboxamide]. PHA-408 is an ATP-competitive inhibitor, which binds IKK-2 tightly
      with a relatively slow off rate. In arthritis-relevant cells and animal models,
      PHA-408 suppresses inflammation-induced cellular events, including IkappaBalpha
      phosphorylation and degradation, p65 phosphorylation and DNA binding activity,
      the expression of inflammatory mediators, and joint pathology. PHA-408 was
      efficacious in a chronic model of arthritis with no adverse effects at maximally
      efficacious doses. Stemming from its ability to bind tightly to IKK-2, as a
      novelty, we demonstrated that PHA-408-mediated inhibition of IKK-2 activity
      correlated very well with its ability to modulate the fate of IKK-2 substrates
      and downstream transcriptional events. We ultimately directly linked IKK-2
      activity ex vivo and in vivo to markers of inflammation with the inhibitor plasma
      concentrations. Thus, PHA-408 represents a powerful tool to further gain insight
      into the mechanisms by which IKK-2 regulates NF-kappaB signaling and validates
      IKK-2 as a therapeutic target.

PMID- 19168711
TI  - Movement variability and the use of nonlinear tools: principles to guide physical
      therapist practice.
AB  - Fields studying movement generation, including robotics, psychology, cognitive
      science, and neuroscience, utilize concepts and tools related to the
      pervasiveness of variability in biological systems. The concepts of variability
      and complexity and the nonlinear tools used to measure these concepts open new
      vistas for physical therapist practice and research in movement dysfunction of
      all types. Because mounting evidence supports the necessity of variability for
      health and functional movement, this perspective article argues for changes in
      the way therapists view variability, both in theory and in action. By providing
      clinical examples, as well as applying existing knowledge about complex systems,
      the aim of this article is to create a springboard for new directions in physical
      therapist research and practice.

PMID- 19168712
TI  - Patient screening by a physical therapist for nonmusculoskeletal hip pain.
AB  - BACKGROUND AND PURPOSE: Mechanical hip pain and disease-based hip pain can have
      similar signs and symptoms, thereby presenting a differential diagnostic
      challenge for clinicians. Hip pain is a common complaint addressed by physical
      therapists; therefore, it would be advantageous for them to be knowledgeable
      about differential diagnosis for hip pain, so that they can screen for possible
      serious conditions outside the realm of physical therapist practice and make the
      appropriate referral. CASE DESCRIPTION: A 77-year-old man was referred for
      physical therapy by his primary care physician (PCP) with diagnoses of lumbar
      spine and left hip osteoarthritis and possible trochanteric bursitis. After the
      examination, the physical therapist determined that the patient should return to
      his PCP for further testing. Findings leading to this conclusion were pain
      severity out of proportion to the reported injury, the presence of night pain, a
      positive "sign of the buttock," and empty end feels of all hip joint motions,
      which represented a noncapsular pattern of joint restriction. OUTCOMES: The
      patient was diagnosed later with primary lung adenocarcinoma with widespread
      metastases. A computerized tomography scan of the left hip revealed a metastatic
      lesion at the left proximal femur. DISCUSSION: Physical therapists' ability to
      adequately screen for conditions requiring examination by a physician can lead to
      a more timely diagnosis of serious medical conditions. Investigators have found
      published descriptions of end feels, capsular versus noncapsular patterns of
      restriction, and the sign of the buttock to be beneficial screening tools for use
      in people with hip, pelvis, or lumbar spine pain.

PMID- 19168713
TI  - A qualitative application of the diffusion of innovations theory to examine
      determinants of guideline adherence among physical therapists.
AB  - BACKGROUND: Evidence-based practice has become a major issue in physical therapy.
      Many evidence-based guidelines, however, are not used extensively after
      dissemination, and interventions aimed at increasing guideline adherence often
      have limited effects. OBJECTIVE: As a prerequisite for changing this situation,
      the aims of this study were to gain an in-depth understanding of the determinants
      of guideline adherence among physical therapists in the Netherlands and to
      evaluate the opportunities of a theoretical framework in this respect. DESIGN AND
      METHODS: This observational study consisted of 3 focus group interviews (n=12,
      10, and 8) between November 2002 and January 2003. Physical therapists were asked
      to discuss their opinions about and experiences with the Dutch guidelines for low
      back pain. Data were analyzed qualitatively using a directed approach to content
      analysis. Both the interview route and the analysis of the interviews were
      informed by Rogers' Diffusion of Innovations Theory. RESULTS: Our study yielded
      in-depth insights into the various determinants of guideline adherence. Overall,
      the participants had rather unfavorable opinions about issues related to the
      dissemination of the guidelines (first phase of the diffusion process) and
      provided relatively little information on the subsequent adoption process (second
      phase of the diffusion process). The theoretical framework appeared to be a
      useful tool to properly structure the focus group interviews, to systematically
      analyze the data collected, and to determine that supplementary interviews would
      be necessary to cover the entire diffusion process. CONCLUSIONS: Our findings
      indicated that the diffusion process of guidelines among physical therapists was
      not yet completed. The use of theory can provide added value to guideline
      implementation studies.

PMID- 19168714
TI  - Hunting for plant nitric oxide synthase provides new evidence of a central role
      for plastids in nitric oxide metabolism.
AB  - Nitric oxide (NO) has emerged as a central signaling molecule in plants and
      animals. However, the long search for a plant NO synthase (NOS) enzyme has only
      encountered false leads. The first works describing a pathogen-induced NOS-like
      plant protein were soon retracted. New hope came from the identification of NOS1,
      an Arabidopsis thaliana protein with an atypical NOS activity that was found to
      be targeted to mitochondria in roots. Although concerns about the NO-producing
      activity of this protein were raised (causing the renaming of the protein to NO
      associated 1), compelling data on its biological role were missing until
      recently. Strong evidence is now available that this protein functions as a
      GTPase that is actually targeted to plastids, where it might be required for
      ribosome function. These and other results support the argument that the
      defective NO production in loss-of-function mutants is an indirect effect of
      interfering with normal plastid functions and that plastids play an important
      role in regulating NO levels in plant cells.

PMID- 19168715
TI  - ARABIDOPSIS DEHISCENCE ZONE POLYGALACTURONASE1 (ADPG1), ADPG2, and QUARTET2 are
      Polygalacturonases required for cell separation during reproductive development
      in Arabidopsis.
AB  - Cell separation is thought to involve degradation of pectin by several hydrolytic
      enzymes, particularly polygalacturonase (PG). Here, we characterize an activation
      tagging line with reduced growth and male sterility caused by increased
      expression of a PG encoded by QUARTET2 (QRT2). QRT2 is essential for pollen grain
      separation and is part of a small family of three closely related endo-PGs in the
      Arabidopsis thaliana proteome, including ARABIDOPSIS DEHISCENCE ZONE
      POLYGALACTURONASE1 (ADPG1) and ADPG2. Functional assays and complementation
      experiments confirm that ADPG1, ADPG2, and QRT2 are PGs. Genetic analysis
      demonstrates that ADPG1 and ADPG2 are essential for silique dehiscence. In
      addition, ADPG2 and QRT2 contribute to floral organ abscission, while all three
      genes contribute to anther dehiscence. Expression analysis is consistent with the
      observed mutant phenotypes. INDEHISCENT (IND) encodes a putative basic helix-loop
      helix required for silique dehiscence, and we demonstrate that the closely
      related HECATE3 (HEC3) gene is required for normal seed abscission and show that
      IND and HEC3 are required for normal expression of ADPG1 in the silique
      dehiscence zone and seed abscission zone, respectively. We also show that
      jasmonic acid and ethylene act together with abscisic acid to regulate floral
      organ abscission, in part by promoting QRT2 expression. These results demonstrate
      that multiple cell separation events, including both abscission and dehiscence,
      require closely related PG genes.

PMID- 19168716
TI  - A novel polyamine acyltransferase responsible for the accumulation of spermidine
      conjugates in Arabidopsis seed.
AB  - Hydroxycinnamic acid amides are a class of secondary metabolites distributed
      widely in plants. We have identified two sinapoyl spermidine derivatives, N-((4'
      O-glycosyl)-sinapoyl),N'-sinapoylspermidine and N,N'-disinapoylspermidine, which
      comprise the two major polyamine conjugates that accumulate in Arabidopsis
      thaliana seed. Using metabolic profiling of knockout mutants to elucidate the
      functions of members of the BAHD acyltransferase family in Arabidopsis, we have
      also identified two genes encoding spermidine disinapoyl transferase (SDT) and
      spermidine dicoumaroyl transferase (SCT) activities. At2g23510, which is
      expressed mainly in seeds, encodes a spermidine sinapoyl CoA acyltransferase
      (SDT) that is required for the production of disinapoyl spermidine and its
      glucoside in Arabidopsis seed. The structurally related BAHD enzyme encoded by
      At2g25150 is expressed specifically in roots and has spermidine coumaroyl CoA
      acyltransferase (SCT) activity both in vitro and in vivo.

PMID- 19168717
TI  - discordia1 and alternative discordia1 function redundantly at the cortical
      division site to promote preprophase band formation and orient division planes in
      maize.
AB  - In plants, cell wall placement during cytokinesis is determined by the position
      of the preprophase band (PPB) and the subsequent expansion of the phragmoplast,
      which deposits the new cell wall, to the cortical division site delineated by the
      PPB. New cell walls are often incorrectly oriented during asymmetric cell
      divisions in the leaf epidermis of maize (Zea mays) discordia1 (dcd1) mutants,
      and this defect is associated with aberrant PPB formation in asymmetrically
      dividing cells. dcd1 was cloned and encodes a putative B'' regulatory subunit of
      the PP2A phosphatase complex highly similar to Arabidopsis thaliana
      FASS/TONNEAU2, which is required for PPB formation. We also identified
      alternative discordia1 (add1), a second gene in maize nearly identical to dcd1.
      While loss of add1 function does not produce a noticeable phenotype, knock down
      of both genes in add1(RNAi) dcd1(RNAi) plants prevents PPB formation and causes
      misorientation of symmetric and asymmetric cell divisions. Immunolocalization
      studies with an antibody that recognizes both DCD1 and ADD1 showed that these
      proteins colocalize with PPBs and remain at the cortical division site through
      metaphase. Our results indicate that DCD1 and ADD1 function in PPB formation,
      that this function is more critical in asymmetrically dividing cells than in
      symmetrically dividing cells, and that DCD1/ADD1 may have other roles in addition
      to promoting PPB formation at the cortical division site.

PMID- 19168718
TI  - Sympathetic neural responses to mental stress: responders, nonresponders and sex
      differences.
AB  - Mental stress consistently increases heart rate (HR) and blood pressure (BP) in
      humans, despite inconsistent sympathetic neural responses that include increases,
      decreases, or no change in muscle sympathetic nerve activity (MSNA). The purpose
      of the present study was to examine associations between MSNA, BP, and HR
      responses to mental stress. Leg MSNA, BP, HR, and perceived stress levels were
      recorded during 3-5 min of mental arithmetic in 82 subjects (53 men and 29
      women). Subjects were divided into positive responders (>or=Delta3 bursts/min; n
      = 40), negative responders (<or=Delta-3 bursts/min; n = 9), and nonresponders (n
      = 33). Mental stress increased MSNA in positive responders (Delta6 +/- 1
      bursts/min), decreased MSNA in negative responders (Delta-6 +/- 1 bursts/min),
      and did not change MSNA in nonresponders (Delta1 +/- 1 bursts/min). Mental stress
      increased mean BP and HR similarly in positive responders (Delta15 +/- 1 mmHg and
      Delta16 +/- 1 beats/min; P < 0.001), nonresponders (Delta15 +/- 1 mmHg and
      Delta19 +/- 2 beats/min; P < 0.001), and negative responders (Delta12 +/- 2 mmHg
      and Delta19 +/- 3 beats/min; P < 0.001). Perceived stress levels and sex
      distributions were similar across responders and nonresponders; thus, perceived
      stress and sex do not appear to influence MSNA during mental stress. However, men
      demonstrated higher increases of mean BP during mental stress when compared with
      women (Delta16 +/- 1 vs. Delta12 +/- 1 mmHg; P < 0.05), despite no differences in
      MSNA responses. In conclusion, our results demonstrate marked differences in MSNA
      responses to mental stress and a disassociation between MSNA and BP responses to
      mental stress, suggesting complex patterns of vascular responsiveness during
      mental stress.

PMID- 19168719
TI  - Sp1-dependent activation of KLF4 is required for PDGF-BB-induced phenotypic
      modulation of smooth muscle.
AB  - There is clear evidence that the phenotypic modulation of smooth muscle cells
      (SMCs) contributes to the pathophysiology of vascular disease. Phenotypic
      modulation refers to the unique ability of SMCs to alter their phenotype in
      response to extracellular stimuli and is hallmarked by the loss of SMC marker
      gene expression. The transcription factor Kruppel-like factor 4 (KLF4) is a known
      powerful negative regulator of SMC marker gene expression that works, in part, by
      decreasing the expression of the serum response factor (SRF) myocardin. KLF4 is
      not expressed in healthy adult SMCs but is increased in SMCs in response to
      vascular injury in vivo or PDGF-BB treatment in vitro. The aim of the present
      study was to determine the molecular mechanisms that regulate the expression of
      KLF4 in phenotypically modulated SMCs. The results demonstrated that the
      transcription factor stimulating protein-1 (Sp1) regulated the expression of KLF4
      in SMCs. The KLF4 promoter contains three consensus Sp1 binding sites. Using a
      series of truncated KLF4 promoters, we showed that only fragments containing
      these Sp1 sites could be activated by PDGF-BB. In addition, overexpression of Sp1
      alone was sufficient to increase the activity of the KLF4 promoter. Moreover,
      inhibiting Sp1 expression with small-interfering RNA attenuated the effects of
      PDGF-BB on KLF4 expression. Mutation of the three Sp1 sites within the KLF4
      promoter abolished both baseline and PDGF-BB-induced activity. Finally, the
      results demonstrated enhanced Sp1 binding to the KLF4 promoter in SMCs treated
      with PDGF-BB in vitro and following vascular injury in vivo. Taken together, the
      results suggest a novel role for Sp1 in increasing the expression of KLF4 in
      phenotypically modulated SMCs.

PMID- 19168720
TI  - Properties and ionic mechanisms of action potential adaptation, restitution, and
      accommodation in canine epicardium.
AB  - Computational models of cardiac myocytes are important tools for understanding
      ionic mechanisms of arrhythmia. This work presents a new model of the canine
      epicardial myocyte that reproduces a wide range of experimentally observed rate
      dependent behaviors in cardiac cell and tissue, including action potential (AP)
      duration (APD) adaptation, restitution, and accommodation. Model behavior depends
      on updated formulations for the 4-aminopyridine-sensitive transient outward
      current (I(to1)), the slow component of the delayed rectifier K(+) current
      (I(Ks)), the L-type Ca(2+) channel current (I(Ca,L)), and the Na(+)-K(+) pump
      current (I(NaK)) fit to data from canine ventricular myocytes. We found that
      I(to1) plays a limited role in potentiating peak I(Ca,L) and sarcoplasmic
      reticulum Ca(2+) release for propagated APs but modulates the time course of APD
      restitution. I(Ks) plays an important role in APD shortening at short diastolic
      intervals, despite a limited role in AP repolarization at longer cycle lengths.
      In addition, we found that I(Ca,L) plays a critical role in APD accommodation and
      rate dependence of APD restitution. Ca(2+) entry via I(Ca,L) at fast rate drives
      increased Na(+)-Ca(2+) exchanger Ca(2+) extrusion and Na(+) entry, which in turn
      increases Na(+) extrusion via outward I(NaK). APD accommodation results from this
      increased outward I(NaK). Our simulation results provide valuable insight into
      the mechanistic basis of rate-dependent phenomena important for determining the
      heart's response to rapid and irregular pacing rates (e.g., arrhythmia). Accurate
      simulation of rate-dependent phenomena and increased understanding of their
      mechanistic basis will lead to more realistic multicellular simulations of
      arrhythmia and identification of molecular therapeutic targets.

PMID- 19168721
TI  - Interaction of vascular smooth muscle cells and monocytes by soluble factors
      synergistically enhances IL-6 and MCP-1 production.
AB  - Inflammatory mechanisms contribute to atherogenesis. Monocyte chemoattractant
      protein (MCP)-1 and IL-6 are potent mediators of inflammation. Both contribute to
      early atherogenesis by luring monocytes and regulating cell functions in the
      vessel wall. MCP-1 and IL-6 production resulting from the interaction of invading
      monocytes with local vessel wall cells may accelerate atherosclerosis. We
      investigated the influence of the interaction of human vascular smooth muscle
      cells (SMCs) with human mononuclear cells (MNCs) or monocytes on IL-6 and MCP-1
      production in a coculture model. Interaction synergistically enhanced IL-6 and
      MCP-1 production (up to 30- and 10-fold, respectively) compared with separately
      cultured cells. This enhancement was mediated by CD14-positive monocytes. It was
      dependent on the SMC-to-MNC/monocyte ratio, and as few as 0.2 monocytes/SMC
      induced the synergism. Synergistic IL-6 production was observed at the protein,
      mRNA, and functional level. It was mediated by soluble factors, and simultaneous
      inhibition of IL-1, TNF-alpha, and IL-6 completely blocked the synergism. IL-1,
      TNF-alpha, and IL-6 were present in the cultures. Blockade of the synergism by
      soluble glycoprotein 130Fc/soluble IL-6 receptor, as well as the induction of
      synergistic IL-6 production by costimulation of SMCs with IL-1, TNF-alpha, and
      hyper-IL-6, suggested the involvement of IL-6 trans-signaling. The contribution
      of IL-6 was consistent with enhanced STAT3 phosphorylation. The present data
      suggest that SMC/monocyte interactions may augment the proinflammatory status in
      the tissue, contributing to the acceleration of early atherogenesis.

PMID- 19168722
TI  - Inhibition of integrin alphavbeta3 prevents urokinase plasminogen activator
      mediated impairment of cerebrovasodilation after cerebral hypoxia/ischemia.
AB  - Cerebral hypoxia (10 min) followed immediately by ischemia (20 min) (H/I) impairs
      cerebrovasodilation in response to hypercapnia and hypotension in the newborn
      pig; exogenous urokinase plasminogen activator (uPA) potentiates this effect,
      whereas the blockade of endogenous uPA-mediated vasoactivity prevents it
      completely. This study investigated the role of integrin alpha(V)beta(3) in the
      uPA-mediated impairment of cerebrovasodilation after H/I in piglets equipped with
      a closed cranial window. Pial artery dilation induced by hypercapnia (Pco(2), 75
      mmHg) and hypotension (mean arterial blood pressure, decreased by 45%) was
      blunted after H/I, reversed to vasconstriction in piglets treated with uPA (10(
      7) M), a concentration observed in cerebrospinal fluid after H/I, but reverted to
      a dilation no different than preinsult in piglets administered an anti
      alpha(V)beta(3) antibody (10 ng/ml) in addition to uPA (26 +/- 1, 9 +/- 1, -10 +/
      3, and 22 +/- 3% for hypercapnia before H/I, after H/I, after H/I with uPA, and
      after H/I with combined uPA and anti-alpha(V)beta(3) antibody, respectively).
      Responses to isoproterenol were unchanged after H/I and combined uPA and anti
      alpha(V)beta(3) antibody. Similar results were obtained for the combined
      administration of uPA with the alpha(V)beta(3) antagonist Arg-Gly-Asp-d-Phe-Val
      and Arg-Gly-Asp-Ser, but not for the inactive analog Arg-Gly-Asp-Glu-Ser acetate.
      These data show that the activation of the integrin alpha(V)beta(3) contributes
      to the uPA-mediated impairment of pial artery dilation after H/I. These data
      suggest that the inhibition of uPA and integrin signaling may preserve
      cerebrohemodynamic control after H/I.

PMID- 19168723
TI  - Hydrogen sulfide triggers late-phase preconditioning in postischemic small
      intestine by an NO- and p38 MAPK-dependent mechanism.
AB  - Hydrogen sulfide (H(2)S) is one of three endogenous gases, along with carbon
      monoxide (CO) and nitric oxide (NO), that exert a variety of important vascular
      actions in vivo. Although it has been demonstrated that CO or NO can trigger the
      development of a preconditioned phenotype in postischemic tissues, it is unclear
      whether H(2)S may also induce protection in organs subsequently exposed to
      ischemia-reperfusion (I/R). In light of these observations, we postulated that
      preconditioning with the exogenous H(2)S donor sodium hydrosulfide (NaHS-PC)
      would inhibit leukocyte rolling (LR) and adhesion (LA) induced by I/R. We used
      intravital microscopic techniques to demonstrate that NaHS-PC 24 h, but not 1 h,
      before I/R causes postcapillary venules to shift to an anti-inflammatory
      phenotype in wild-type (WT) mice such that these vessels fail to support LR and
      LA during reperfusion. The protective effect of NaHS-PC on LR was largely
      abolished by coincident pharmacological inhibition of NO synthase (NOS) in WT
      animals and was absent in endothelial NOS-deficient (eNOS(-/-)) mice. A similar
      pattern of response was noted in WT mice treated concomitantly with NaHS plus p38
      mitogen-activated protein kinase (MAPK) inhibitors (SB 203580 or SK-86002).
      Whereas the reduction in LA induced by antecedent NaHS was attenuated by
      pharmacological inhibition of NOS or p38 MAPK in WT mice, the antiadhesive effect
      of NaHS was still evident in eNOS(-/-) mice. Thus NaHS-PC prevents LR and LA by
      triggering the activation of an eNOS- and p38 MAPK-dependent mechanism. However,
      the role of eNOS in the antiadhesive effect of NaHS-PC was less prominent than
      its effect to reduce LR.

PMID- 19168724
TI  - Coronary blood flow responses to physiological stress in humans.
AB  - Animal reports suggest that reflex activation of cardiac sympathetic nerves can
      evoke coronary vasoconstriction. Conversely, physiological stress may induce
      coronary vasodilation to meet an increased metabolic demand. Whether the
      sympathetic nervous system can modulate coronary vasomotor tone in response to
      stress in humans is unclear. Coronary blood velocity (CBV), an index of coronary
      blood flow, can be measured in humans by noninvasive duplex ultrasound. We
      studied 11 healthy volunteers and measured beat-by-beat changes in CBV, blood
      pressure, and heart rate during 1) static handgrip for 20 s at 10% and 70% of
      maximal voluntary contraction; 2) lower body negative pressure at -10 and -30
      mmHg for 3 min each; 3) cold pressor test for 90 s; and 4) hypoxia (10% O(2)),
      hyperoxia (100% O(2)), and hypercapnia (5% CO(2)) for 5 min each. At the higher
      level of handgrip, mean blood pressure increased (P < 0.001), whereas CBV did not
      change [P = not significant (NS)]. In addition, during lower body negative
      pressure, CBV decreased (P < 0.02; and P < 0.01, for -10 and -30 mmHg,
      respectively), whereas blood pressure did not change (P = NS). The dissociation
      between the responses of CBV and blood pressure to handgrip and lower body
      negative pressure is consistent with coronary vasoconstriction. During hypoxia,
      CBV increased (P < 0.02) and decreased during hyperoxia (P < 0.01), although
      blood pressure did not change (P = NS), suggesting coronary vasodilation during
      hypoxia and vasoconstriction during hyperoxia. In contrast, concordant increases
      in CBV and blood pressure were noted during the cold pressor test, and
      hypercapnia had no effects on either parameter. Thus the physiological stress
      known to be associated with sympathetic activation can produce coronary
      vasoconstriction in humans. Contrasting responses were noted during systemic
      hypoxia and hyperoxia where mechanisms independent of autonomic influences appear
      to dominate the vascular end-organ effects.

PMID- 19168725
TI  - Impaired hemodynamics and endothelial vasomotor function via endoperoxide
      mediated vasoconstriction in the carotid artery of spontaneously hypertensive
      rats.
AB  - The fact that endothelium removal increases diameter and compliance in the common
      carotid artery (CCA) of spontaneously hypertensive rats (SHR) and that improving
      CCA endothelium-dependent vasorelaxation has been shown to normalize a reduced
      systolic blood flow through the SHR CCA compared with normotensive Wistar-Kyoto
      rats (WKY) suggests that endothelial vasomotor dysfunction may be linked to
      altered large artery hemodynamics in hypertension. The experiments herein were
      designed to further investigate WKY and SHR CCA hemodynamics and endothelium
      dependent vasomotor functions. It was hypothesized that CCA blood flow and
      conductance would be reduced throughout the cardiac cycle in SHR and that
      endothelium-dependent contractile activity would impair SHR CCA vasorelaxation.
      We report that mean, maximal systolic, and diastolic blood flow was reduced in
      SHR vs. WKY CCA, as was vascular conductance. Pressure was augmented in SHR CCA
      and accompanied by late systolic flow augmentation so that total flow during
      systole was indeed no different between strains, possibly explained by earlier
      lower body wave reflection. While ACh stimulation in isolated precontracted WKY
      CCA caused a robust nitric oxide (NO)-mediated vasorelaxation, endothelium
      dependent, cyclooxygenase (COX)-mediated contractile activity stimulated by high
      ACh concentration impaired NO- and non-NO/non-COX-mediated vasorelaxation in
      precontracted SHR CCA. In quiescent CCA, this endothelium-dependent contractile
      response was COX-1 and thromboxane-prostanoid receptor mediated and modulated by
      the availability of NO. These data collectively suggest that endothelium
      dependent, COX-mediated endoperoxide signaling in the CCA of SHR may elicit
      vasoconstriction, which could shift the mechanical properties of this conduit
      artery and contribute to reduced CCA blood flow in vivo.

PMID- 19168726
TI  - Muscle ring finger 1 mediates cardiac atrophy in vivo.
AB  - Pathological cardiac hypertrophy, induced by various etiologies such as high
      blood pressure and aortic stenosis, develops in response to increased afterload
      and represents a common intermediary in the development of heart failure.
      Understandably then, the reversal of pathological cardiac hypertrophy is
      associated with a significant reduction in cardiovascular event risk and
      represents an important, yet underdeveloped, target of therapeutic research.
      Recently, we determined that muscle ring finger-1 (MuRF1), a muscle-specific
      protein, inhibits the development of experimentally induced pathological; cardiac
      hypertrophy. We now demonstrate that therapeutic cardiac atrophy induced in
      patients after left ventricular assist device placement is associated with an
      increase in cardiac MuRF1 expression. This prompted us to investigate the role of
      MuRF1 in two independent mouse models of cardiac atrophy: 1) cardiac hypertrophy
      regression after reversal of transaortic constriction (TAC) reversal and 2)
      dexamethasone-induced atrophy. Using echocardiographic, histological, and gene
      expression analyses, we found that upon TAC release, cardiac mass and
      cardiomyocyte cross-sectional areas in MuRF1(-/-) mice decreased approximately
      70% less than in wild type mice in the 4 wk after release. This was in striking
      contrast to wild-type mice, who returned to baseline cardiac mass and
      cardiomyocyte size within 4 days of TAC release. Despite these differences in
      atrophic remodeling, the transcriptional activation of cardiac hypertrophy
      measured by beta-myosin heavy chain, smooth muscle actin, and brain natriuretic
      peptide was attenuated similarly in both MuRF1(-/-) and wild-type hearts after
      TAC release. In the second model, MuRF1(-/-) mice also displayed resistance to
      dexamethasone-induced cardiac atrophy, as determined by echocardiographic
      analysis. This study demonstrates, for the first time, that MuRF1 is essential
      for cardiac atrophy in vivo, both in the setting of therapeutic regression of
      cardiac hypertrophy and dexamethasone-induced atrophy.

PMID- 19168728
TI  - Suppression of nitrosative and oxidative stress to reduce cardiac allograft
      vasculopathy.
AB  - Oxidant injury occurs when an organ is severed from its native blood supply and
      then reperfused and continues during subsequent periods of immune attack.
      Experiments here test the hypothesis that an antioxidant given only in the peri
      reperfusion period protects against not only oxidative but also nitrosative
      stress, leading to reduced vasculopathy long after cardiac allotransplantation.
      Experiments were performed using a murine heterotopic cardiac transplantation
      model. An antioxidant, in the form of intraperitoneal high-dose riboflavin, was
      given to recipients during the initial 3 days after transplantation. Antioxidant
      treated mice showed significantly longer graft survival than control mice. At 4 h
      after transplantation, antioxidant treatment significantly reduced graft lipid
      peroxidation and oxidized DNA and preserved antioxidant enzyme activity. At day 6
      posttransplantation, the redox-sensitive transcription factor nuclear factor
      kappaB and inducible nitric oxide synthase were significantly reduced following
      antioxidant treatment, with concomitant reduction of nitrotyrosine. Despite the
      limited duration of antioxidant treatment, both acute and chronic rejection were
      significantly suppressed. In vitro experiments confirmed suppression of
      nitrosative and oxidative stress and cardiomyocyte damage in antioxidant-treated
      cardiac allografts. Collectively, antioxidant administration during the initial 3
      days after transplantation significantly reduces nitrosative and oxidative stress
      in cardiac allografts, modulates immune responses, and protects against
      vasculopathy.

PMID- 19168727
TI  - NADPH oxidase contributes to coronary endothelial dysfunction in the failing
      heart.
AB  - Increased reactive oxygen species (ROS) produced by the failing heart can react
      with nitric oxide (NO), thereby decreasing NO bioavailability. This study tested
      the hypothesis that increased ROS generation contributes to coronary endothelial
      dysfunction in the failing heart. Congestive heart failure (CHF) was produced in
      six dogs by ventricular pacing at 240 beats/min for 4 wk. Studies were performed
      at rest and during treadmill exercise under control conditions and after
      treatment with the NADPH oxidase inhibitor and antioxidant apocynin (4 mg/kg iv).
      Apocynin caused no significant changes in heart rate, aortic pressure, left
      ventricular (LV) systolic pressure, LV end-diastolic pressure, or maximum rate of
      LV pressure increase at rest or during exercise in normal or CHF dogs. Apocynin
      caused no change in coronary blood flow (CBF) in normal dogs but increased CBF at
      rest and during exercise in animals with CHF (P < 0.05). Intracoronary ACh caused
      dose-dependent increases of CBF that were blunted in CHF. Apocynin had no effect
      on the response to ACh in normal dogs but augmented the response to ACh in CHF
      dogs (P < 0.05). The oxidative stress markers nitrotyrosine and 4-hydroxy-2
      nonenal were significantly greater in failing than in normal myocardium.
      Furthermore, coelenterazine chemiluminescence for O(2)(-) was more than twice
      normal in failing myocardium, and this difference was abolished by apocynin.
      Western blot analysis of myocardial lysates demonstrated that the p47(phox) and
      p22(phox) subunits of NADPH were significantly increased in the failing hearts,
      while real-time PCR demonstrated that Nox2 mRNA was significantly increased. The
      data indicate that increased ROS generation in the failing heart is associated
      with coronary endothelial dysfunction and suggest that NADPH oxidase may
      contribute to this abnormality.

PMID- 19168729
TI  - Peroxide generation by p47phox-Src activation of Nox2 has a key role in protein
      kinase C-induced arterial smooth muscle contraction.
AB  - Protein kinase C (PKC) stimulation of NAD(P)H oxidases (Nox) is an important
      component of multiple vascular disease processes; however, the relationship
      between oxidase activation and the regulation of vascular smooth muscle
      contraction by PKC remains poorly understood. Therefore, we examined the
      signaling cascade of PKC-elicited Nox activation and the role of superoxide and
      hydrogen peroxide in mediating PKC-induced vascular contraction. Endothelium
      denuded bovine coronary arteries showed a PKC-dependent basal production of
      lucigenin (5 muM)-detected Nox oxidase-derived superoxide, which was stimulated
      fourfold by PKC activation with 10 muM phorbol 12,13-dibutyrate (PDBu). PDBu
      appeared to increase superoxide generation by Nox2 through both p47(phox) and
      peroxide-dependent Src activation mechanisms based on the actions of inhibitors,
      properties of Src phosphorylation, and the loss of responses in aorta from mice
      deficient in Nox2 and p47(phox). The actions of inhibitors of contractile
      regulating mechanisms, scavengers of superoxide and peroxide, and responses in
      knockout mouse aortas suggest that a major component of the contraction elicited
      by PDBu appeared to be mediated through peroxide derived from Nox2 activation
      stimulating force generation through Rho kinase and calmodulin kinase-II
      mechanisms. Superoxide generated by PDBu also attenuated relaxation to
      nitroglycerin. Peroxide-derived from Nox2 activation by PKC appeared to be a
      major contributor to the thromboxane A(2) receptor agonist U46619 (100 nM)
      elicited contraction of coronary arteries. Thus a p47(phox) and Src kinase
      activation of peroxide production by Nox2 appears to be an important contributor
      to vascular contractile mechanisms mediated through activation of PKC.

PMID- 19168730
TI  - Is erythropoietin behind maladaptive anemic heart failure?

PMID- 19168731
TI  - The RgpA-Kgp proteinase-adhesin complexes of Porphyromonas gingivalis Inactivate
      the Th2 cytokines interleukin-4 and interleukin-5.
AB  - The RgpA-Kgp proteinase-adhesin complexes are a primary virulence factor of
      Porphyromonas gingivalis, a major pathogen in the development of chronic
      periodontitis. The RgpA-Kgp complexes have been suggested to bias the immune
      response to a Th2 phenotype in disease by hydrolysis of Th1 cytokines. Here, we
      show that the RgpA-Kgp complexes hydrolyze and inactivate interleukin-4 (IL-4)
      and IL-5 under physiologically relevant conditions. Using the IL-4/IL-5-dependent
      TF1.8 T-cell line, it was found that at equimolar ratios of cytokine to RgpA-Kgp
      complexes, IL-4 and IL-5 were inactivated in the culture medium. The inactivation
      of IL-4 and IL-5 was RgpA-Kgp concentration dependent, as at an enzyme-to
      cytokine molar ratio of 1:8, the bioactivity of the cytokines was greater than at
      the higher concentration of RgpA-Kgp of 1:1. Furthermore, inactivation of the
      cytokines by the RgpA-Kgp complexes was time dependent, as longer preincubation
      times resulted in lower cytokine activity. IL-5 was found to be slightly more
      resistant to inactivation than IL-4. Mass spectrometric analyses of IL-4 and IL-5
      showed that hydrolysis by RgpA-Kgp complexes was C terminal to Arg and Lys
      residues of the cytokines. The peptides released indicated that the regions of IL
      4 and IL-5 important for bioactivity were being hydrolyzed in the first 15 min of
      incubation. The ability of the RgpA-Kgp complexes to degrade Th2 cytokines may
      contribute to immune dysregulation and may play a role in the pathology of
      chronic periodontitis.

PMID- 19168732
TI  - Salmonella enterica serovar Typhimurium mutants unable to convert malate to
      pyruvate and oxaloacetate are avirulent and immunogenic in BALB/c mice.
AB  - Previously, we showed that the Salmonella enterica serovar Typhimurium SR-11
      tricarboxylic acid (TCA) cycle must operate as a complete cycle for full
      virulence after oral infection of BALB/c mice (M. Tchawa Yimga, M. P. Leatham, J.
      H. Allen, D. C. Laux, T. Conway, and P. S. Cohen, Infect. Immun. 74:1130-1140,
      2006). In the same study, we showed that for full virulence, malate must be
      converted to both oxaloacetate and pyruvate. Moreover, it was recently
      demonstrated that blocking conversion of succinyl-coenzyme A to succinate
      attenuates serovar Typhimurium SR-11 but does not make it avirulent; however,
      blocking conversion of succinate to fumarate renders it completely avirulent and
      protective against subsequent oral infection with the virulent serovar
      Typhimurium SR-11 wild-type strain (R. Mercado-Lubo, E. J. Gauger, M. P. Leatham,
      T. Conway, and P. S. Cohen, Infect. Immun. 76:1128-1134, 2008). Furthermore, the
      ability to convert succinate to fumarate appeared to be required only after
      serovar Typhimurium SR-11 became systemic. In the present study, evidence is
      presented that serovar Typhimurium SR-11 mutants that cannot convert fumarate to
      malate or that cannot convert malate to both oxaloacetate and pyruvate are also
      avirulent and protective in BALB/c mice. These results suggest that in BALB/c
      mice, the malate that is removed from the TCA cycle in serovar Typhimurium SR-11
      for conversion to pyruvate must be replenished by succinate or one of its
      precursors, e.g., arginine or ornithine, which might be available in mouse
      phagocytes.

PMID- 19168733
TI  - Intralesional regulatory T-cell suppressive function during human acute and
      chronic cutaneous leishmaniasis due to Leishmania guyanensis.
AB  - The levels of regulatory T cells (Treg cells), analyzed by Foxp3 mRNA expression,
      were determined in lesions from patients with acute cutaneous leishmaniasis (ACL)
      and chronic cutaneous leishmaniasis (CCL). We demonstrated that Treg cells
      preferentially accumulate in lesions from ACL patients during the early phase of
      infection (lesion duration of less than 1 month). In addition, levels of Foxp3
      mRNA transcripts were significantly higher in specimens from patients with CCL
      than in those from patients with ACL, suggesting a critical role of intralesional
      Treg cells in CCL. Intralesional Treg cells from both ACL and CCL patients were
      shown to have suppressive functions in vitro, since they inhibited the gamma
      interferon (IFN-gamma) produced by CD4(+) CD25(-) T cells purified from
      peripheral blood mononuclear cells from the same patient in response to
      Leishmania guyanensis stimulation. Intralesional 2,3-indoleamine dioxygenase
      (IDO) mRNA expression was associated with that of Foxp3, suggesting a role for
      IDO in the suppressive activity of intralesional Treg cells. In addition, a role,
      albeit minor, of interleukin-10 (IL-10) was also demonstrated, since
      neutralization of IL-10 produced by intralesional T cells increased IFN-gamma
      production by effector cells in an in vitro suppressive assay. These results
      confirm the role of intralesional Treg cells in the immunopathogenesis of human
      Leishmania infection, particularly in CCL patients.

PMID- 19168734
TI  - Killed but metabolically active Bacillus anthracis vaccines induce broad and
      protective immunity against anthrax.
AB  - Bacillus anthracis is the causative agent of anthrax. We have developed a novel
      whole-bacterial-cell anthrax vaccine utilizing B. anthracis that is killed but
      metabolically active (KBMA). Vaccine strains that are asporogenic and nucleotide
      excision repair deficient were engineered by deleting the spoIIE and uvrAB genes,
      rendering B. anthracis extremely sensitive to photochemical inactivation with S
      59 psoralen and UV light. We also introduced point mutations into the lef and cya
      genes, which allowed inactive but immunogenic toxins to be produced.
      Photochemically inactivated vaccine strains maintained a high degree of metabolic
      activity and secreted protective antigen (PA), lethal factor, and edema factor.
      KBMA B. anthracis vaccines were avirulent in mice and induced less injection site
      inflammation than recombinant PA adsorbed to aluminum hydroxide gel. KBMA B.
      anthracis-vaccinated animals produced antibodies against numerous anthrax
      antigens, including high levels of anti-PA and toxin-neutralizing antibodies.
      Vaccination with KBMA B. anthracis fully protected mice against challenge with
      lethal doses of toxinogenic unencapsulated Sterne 7702 spores and rabbits against
      challenge with lethal pneumonic doses of fully virulent Ames strain spores.
      Guinea pigs vaccinated with KBMA B. anthracis were partially protected against
      lethal Ames spore challenge, which was comparable to vaccination with the
      licensed vaccine anthrax vaccine adsorbed. These data demonstrate that KBMA
      anthrax vaccines are well tolerated and elicit potent protective immune
      responses. The use of KBMA vaccines may be broadly applicable to bacterial
      pathogens, especially those for which the correlates of protective immunity are
      unknown.

PMID- 19168736
TI  - Vaccination route that induces transforming growth factor beta production fails
      to elicit protective immunity against Leishmania donovani infection.
AB  - BALB/c mice immunized intraperitoneally (i.p.) and intravenously (i.v.) with
      Leishmania donovani promastigote membrane antigens (LAg), either free or
      encapsulated in liposomes, were protected against challenge infection with L.
      donovani, whereas mice immunized by the subcutaneous (s.c.) and intramuscular
      routes were not protected. Protected mice showed strong parasite resistance in
      both the liver and spleen, along with enhanced immunoglobulin G2a and delayed
      type hypersensitivity responses. Again, mice vaccinated through the i.p. and i.v.
      routes showed high levels of NO production after challenge infection. s.c.
      vaccination resulted in an increased capacity of the spleen cells to produce
      prechallenge transforming growth factor beta (TGF-beta) levels during the in
      vitro antigen recall response, whereas i.p. immunization induced production of
      prechallenge gamma interferon, interleukin-12 (IL-12), and IL-4 levels, with a
      Th1 bias. Exposure to antigen-stimulated splenocyte supernatants of i.p. but not
      s.c. immunized mice activated macrophages for in vitro parasite killing. As an
      enhanced level of TGF-beta was detected in supernatants from unprotected s.c.
      immunized mice, neutralization by anti-TGF-beta antibody enhanced in vitro
      macrophage killing activity. The suppressive role of this cytokine was evaluated
      in vivo by vaccination with liposomal LAg and anti-TGF-beta antibody. Upon
      parasite challenge, these animals showed significant protection in both the liver
      and spleen. Moreover, the addition of recombinant TGF-beta in splenocyte
      supernatants of i.p. immunized mice in vitro as well as in vivo inhibited the
      protective ability of the macrophages by the i.p. route. Thus, the induction of
      high prechallenge TGF-beta limits the efficacy of vaccination by routes that are
      nonprotective.

PMID- 19168735
TI  - Host-parasite interactions in trypanosomiasis: on the way to an antidisease
      strategy.

PMID- 19168737
TI  - Direct regulation by the Vibrio cholerae regulator ToxT to modulate colonization
      and anticolonization pilus expression.
AB  - The pathogen Vibrio cholerae uses a large number of coordinated transcriptional
      regulatory events to transition from its environmental reservoir to the host and
      establish itself at its preferred colonization site at the host intestinal
      mucosa. The key regulator in this process is the AraC/XylS family transcription
      factor, ToxT, which plays critical roles in pathogenesis, including the
      regulation of two type IV pili, the anticolonization factor mannose-sensitive
      hemagglutinin and the toxin-coregulated pilus. Previously, it was thought ToxT
      required dimerization in order to effect transcriptional regulation at its
      cognate promoters. Here, we present evidence that ToxT directly represses
      transcription of the msh operon by binding to three promoters within this operon
      and that dimerization may not be required for transcriptional repression of
      target promoters by ToxT, suggesting that this regulator uses different
      mechanisms to modulate the transcriptional repertoire of V. cholerae.

PMID- 19168738
TI  - Identification of novel glycosyltransferases required for assembly of the
      Pasteurella multocida A:1 lipopolysaccharide and their involvement in virulence.
AB  - We previously determined the structure of the Pasteurella multocida Heddleston
      type 1 lipopolysaccharide (LPS) molecule and characterized some of the
      transferases essential for LPS biosynthesis. We also showed that P. multocida
      strains expressing truncated LPS display reduced virulence. Here, we have
      identified all of the remaining glycosyltransferases required for synthesis of
      the oligosaccharide extension of the P. multocida Heddleston type 1 LPS,
      including a novel alpha-1,6 glucosyltransferase, a beta-1,4 glucosyltransferase,
      a putative bifunctional galactosyltransferase, and two heptosyltransferases. In
      addition, we identified a novel oligosaccharide extension expressed only in a
      heptosyltransferase (hptE) mutant background. All of the analyzed mutants
      expressing LPS with a truncated main oligosaccharide extension displayed reduced
      virulence, but those expressing LPS with an intact heptose side chain were able
      to persist for long periods in muscle tissue. The hptC mutant, which expressed
      LPS with the shortest oligosaccharide extension and no heptose side chain, was
      unable to persist on the muscle or cause any disease. Furthermore, all of the
      mutants displayed increased sensitivity to the chicken antimicrobial peptide
      fowlicidin 1, with mutants expressing highly truncated LPS being the most
      sensitive.

PMID- 19168739
TI  - Efficacy of opsonic and nonopsonic serotype 3 pneumococcal capsular
      polysaccharide-specific monoclonal antibodies against intranasal challenge with
      Streptococcus pneumoniae in mice.
AB  - Serotype-specific antibodies to pneumococcal capsular polysaccharide (PPS) are a
      critical component of vaccine-mediated immunity to Streptococcus pneumoniae. In
      this study, we investigated the in vitro opsonophagocytic activities of three PPS
      specific mouse immunoglobulin G1 monoclonal antibodies (MAbs), 1E2, 5F6, and 7A9,
      and determined their in vivo efficacies against intranasal challenge with WU2, a
      serotype 3 pneumococcal strain, in normal and immunodeficient mice. The MAbs had
      different in vitro activities in a pneumococcal killing assay: 7A9 enhanced
      killing by mouse neutrophils and J774 cells in the presence of a complement
      source, whereas 5F6 promoted killing in the absence, but not the presence, of
      complement, and 1E2 did not promote killing under any conditions. Nonetheless,
      all three MAbs protected normal and complement component 3-deficient mice from a
      lethal intranasal challenge with WU2 in passive-immunization experiments in which
      10 mug of the MAbs were administered intraperitoneally before intranasal
      challenge. In contrast, only 1E2 protected Fcgamma receptor IIB knockout
      (FcgammaRIIB KO) mice and mice that were depleted of neutrophils with the MAb
      RB6, whereas 7A9 and 5F6 required neutrophils and FcgammaRIIB to mediate
      protection. Conversely, 7A9 and 5F6 protected FcgammaR KO mice, but 1E2 did not.
      Hence, the efficacy of 1E2 required an activating FcgammaR(s), whereas 5F6 and
      7A9 required the inhibitory FcgammaR (FcgammaRIIB). Taken together, our data
      demonstrate that both MAbs that do and do not promote pneumococcal killing in
      vitro can mediate protection in vivo, although their efficacies depend on
      different host receptors and/or components.

PMID- 19168740
TI  - Preferential brain homing following intranasal administration of Trypanosoma
      cruzi.
AB  - The Chagas' disease parasite Trypanosoma cruzi commonly infects humans through
      skin abrasions or mucosa from reduviid bug excreta. Yet most studies on animal
      models start with subcutaneous or intraperitoneal injections, a distant
      approximation of the skin abrasion route. We show here that atraumatic placement
      of T. cruzi in the mouse nasal cavity produced low parasitemia, high survival
      rates, and preferential brain invasion compared to the case with subcutaneously
      injected parasites. Brain invasion was particularly prominent in the basal
      ganglia, peaked at a time when parasitemia was no longer detectable, and elicited
      a relatively large number of inflammatory foci. Yet, based on motor behavioral
      parameters and staining with Fluoro-Jade C, a dye that specifically recognizes
      apoptotic and necrotic neurons, brain invasion did not cause neurodegenerative
      events, in contrast to the neurodegeneration in the enteric nervous system. The
      results indicate that placement of T. cruzi on the mucosa in the mouse nasal
      cavity establishes a systemic infection with a robust yet harmless infection of
      the brain, seemingly analogous to disease progression in humans. The model may
      facilitate studies designed to understand mechanisms underlying T. cruzi
      infection of the central nervous system.

PMID- 19168741
TI  - Impaired innate and adaptive immunity to Streptococcus pneumoniae and its effect
      on colonization in an infant mouse model.
AB  - Streptococcus pneumoniae colonization and invasive disease peak around the third
      and first birthdays, respectively, and decline thereafter. While these declines
      are attributable in part to immunity acquired via natural exposure, maturation of
      innate immune responses may also be involved. A mucosally administered candidate
      whole-cell pneumococcal vaccine (WCV) containing killed pneumococcal antigen
      (WCA) plus a cholera toxin adjuvant protects against intranasal carriage of
      pneumococci by a mechanism that is antibody independent and CD4(+) TH17 cell
      dependent. Because infants and children are a key target population for this
      vaccine, we sought to evaluate the immune responses of neonatal and infant mice
      to S. pneumoniae and to assess whether the WCV would be effective in these mice.
      Like human infants, infant mice showed impaired clearance of nasopharyngeal
      colonization with S. pneumoniae. Macrophages from neonatal and infant mice
      stimulated with killed pneumococci in vitro showed significantly reduced cytokine
      production, including that of KC, granulocyte colony-stimulating factor,
      granulocyte-macrophage colony-stimulating factor, macrophage chemoattractant
      protein 1, interleukin-6 (IL-6), IL-1alpha, tumor necrosis factor alpha, and
      gamma interferon, whereas IL-10 expression was significantly increased compared
      to that in macrophages from adult mice. IL-17A production from adult immune
      CD4(+) T cells was significantly delayed when neonatal macrophages instead of
      adult macrophages were used as antigen-presenting cells. Moreover, whole blood
      from mice immunized as neonates with WCV produced significantly less IL-17A after
      stimulation with WCA than did blood from mice immunized as adults. Nonetheless, a
      single immunization of neonatal mice with WCV significantly reduced colonization
      density. Overall, our data suggest an impairment of both innate and acquired
      cellular immune responses in neonatal and infant mice. However, WCV confers a
      significant reduction in colonization following pneumococcal challenge,
      suggesting that it may still be effective in the setting of immature immune
      responses.

PMID- 19168742
TI  - Pseudomonas aeruginosa infection of zebrafish involves both host and pathogen
      determinants.
AB  - Zebrafish (Danio rerio) have a number of strengths as a host model for infection,
      including genetic tractability, a vertebrate immune system similar to that of
      mammals, ease and scale of laboratory handling, which allows analysis with
      reasonable throughput, and transparency, which facilitates visualization of the
      infection. With these advantages in mind, we examined whether zebrafish could be
      used to study Pseudomonas aeruginosa pathogenesis and found that infection of
      zebrafish embryos with live P. aeruginosa (PA14 or PAO1) by microinjection
      results in embryonic death, unlike infection with Escherichia coli or heat-killed
      P. aeruginosa, which has no effect. Similar to studies with mice, P. aeruginosa
      mutants deficient in type three secretion (pscD) or quorum sensing (lasR and
      mvfR) are attenuated in zebrafish embryos infected at 50 h postfertilization
      (hpf), a developmental stage when both macrophages and neutrophils are present.
      In contrast, embryos infected at 28 hpf, when only macrophages are initially
      present, succumb to lethal challenge with far fewer P. aeruginosa cells than
      those required for embryos infected at 50 hpf, are susceptible to infection with
      lasR and pscD deletion mutants, and are moderately resistant to infection with an
      mvfR mutant. Finally, we show that we can control the outcome of infection
      through the use of morpholinos, which allow us to shift immune cell numbers, or
      small molecules (antibiotics), which rescue embryos from lethal challenge. Thus,
      zebrafish are a novel host model that is well suited for studying the
      interactions among individual pathogenic functions of P. aeruginosa, the role of
      individual components of host immune defense, and small-molecule modulators of
      infection.

PMID- 19168743
TI  - Host complement regulatory protein CD59 is transported to the chlamydial
      inclusion by a Golgi apparatus-independent pathway.
AB  - Chlamydia is an obligate intracellular bacterium that grows and replicates inside
      a cytoplasmic inclusion. We report that a host protein, CD59, which regulates
      complement function at the surfaces of uninfected cells, can be detected at the
      membrane of the chlamydial inclusion. This localization to the inclusion membrane
      was specific for CD59 and not a general feature of other
      glycosylphosphatidylinositol (GPI)-anchored proteins or representative cell
      surface proteins. Using differential permeabilization studies, we showed that
      CD59 is localized to the luminal but not the cytoplasmic face of the inclusion
      membrane, consistent with membrane association via its GPI anchor. Furthermore,
      CD59 was present at the inclusion even when we prevented it from associating with
      membrane microdomains via the GPI anchor or when we inhibited general protein
      transport to the cell surface, indicating that a conventional Golgi apparatus
      dependent trafficking mechanism was not involved. Based on these findings, we
      propose that selected host proteins are trafficked to the inclusion by a Golgi
      apparatus-independent pathway during a Chlamydia infection.

PMID- 19168744
TI  - Role of deoxyribose catabolism in colonization of the murine intestine by
      pathogenic Escherichia coli strains.
AB  - We previously suggested that the ability to metabolize deoxyribose, a phenotype
      encoded by the deoK operon, is associated with the pathogenic potential of
      Escherichia coli strains. Carbohydrate metabolism is thought to provide the
      nutritional support required for E. coli to colonize the intestine. We therefore
      investigated the role of deoxyribose catabolism in the colonization of the gut,
      which acts as a reservoir, by pathogenic E. coli strains. Molecular and
      biochemical characterization of 1,221 E. coli clones from various collections
      showed this biochemical trait to be common in the E. coli species (33.6%).
      However, multivariate analysis evidenced a higher prevalence of sugar
      metabolizing E. coli clones in the stools of patients from countries in which
      intestinal diseases are endemic. Diarrhea processes frequently involve the
      destruction of intestinal epithelia, so it is plausible that such clones may be
      positively selected for in intestines containing abundant DNA, and consequently
      deoxyribose. Statistical analysis also indicated that symptomatic clinical
      disorders and the presence of virulence factors specific to extraintestinal
      pathogenic E. coli were significantly associated with an increased risk of
      biological samples and clones testing positive for deoxyribose. Using the
      streptomycin-treated-mouse model of intestinal colonization, we demonstrated the
      involvement of the deoK operon in gut colonization by two pathogenic isolates
      (one enteroaggregative and one uropathogenic strain). These results, indicating
      that deoxyribose availability promotes pathogenic E. coli growth during host
      colonization, suggest that the acquisition of this trait may be an evolutionary
      step enabling these pathogens to colonize and persist in the mammalian intestine.

PMID- 19168745
TI  - NIH peer review reform--change we need, or lipstick on a pig?

PMID- 19168746
TI  - Gamma interferon and interleukin-1 receptor 1 regulate neutrophil recruitment to
      the corneal stroma in a murine model of Onchocerca volvulus keratitis.
AB  - Toll-like receptor 2 (TLR2) is an essential mediator of corneal inflammation
      induced by the filarial nematode Onchocerca volvulus, which harbors endosymbiotic
      Wolbachia bacteria. TLR2 is also required for dendritic cell activation, gamma
      interferon (IFN-gamma) production, and neutrophil recruitment to the cornea. To
      examine the role of IFN-gamma in O. volvulus keratitis, C57BL/6 and IFN-gamma(-/
      ) mice were immunized subcutaneously, and a soluble antigen extract from O.
      volvulus adult worms (OvAg) was injected into the corneal stroma of each animal.
      We found that, in the absence of IFN-gamma, neutrophil recruitment to the cornea
      was significantly impaired, whereas there was no effect on eosinophil
      infiltration. Since the cornea contains resident macrophages and fibroblasts and
      our previous studies showed that CXC chemokines mediate neutrophil recruitment,
      we examined the role of recombinant IFN-gamma (rIFN-gamma) on each cell type. We
      found no effect of rIFN-gamma on CXC chemokine production by macrophages or
      corneal fibroblasts, either alone or with filarial extracts; in contrast, rIFN
      gamma was found to enhance OvAg-induced tumor necrosis factor alpha (TNF-alpha),
      interleukin-6 (IL-6), IL-1alpha, and IL-1beta in macrophages. Furthermore, we
      found that rTNF-alpha, rIL-1alpha, or rIL-1beta induced CXC chemokine production
      by corneal fibroblasts but not by macrophages. To determine the relative
      contributions of endogenous cytokines, we injected OvAg into the corneal stroma
      of C57BL/6, IL-1 receptor 1(-/-) (IL-1R1(-/-)), and TNF-alphaR1/2(-/-) mice and
      examined neutrophil recruitment. We found that neutrophil infiltration was
      impaired in IL-1R1(-/-) mice but not in TNF-alphaR1/2(-/-) mice. IFN-gamma
      therefore appears to regulate neutrophil recruitment to the corneal stroma by
      enhancing TLR2 expression and OvAg-induced IL-1alpha and IL-1beta production by
      macrophages in the cornea, which then induce IL-1R1-dependent production of CXC
      chemokine by resident corneal fibroblasts.

PMID- 19168747
TI  - Burkholderia mallei tssM encodes a putative deubiquitinase that is secreted and
      expressed inside infected RAW 264.7 murine macrophages.
AB  - Burkholderia mallei, a category B biothreat agent, is a facultative intracellular
      pathogen that causes the zoonotic disease glanders. The B. mallei VirAG two
      component regulatory system activates the transcription of approximately 60
      genes, including a large virulence gene cluster encoding a type VI secretion
      system (T6SS). The B. mallei tssM gene encodes a putative ubiquitin-specific
      protease that is physically linked to, and transcriptionally coregulated with,
      the T6SS gene cluster. Mass spectrometry and immunoblot analysis demonstrated
      that TssM was secreted in a virAG-dependent manner in vitro. Surprisingly, the
      T6SS was found to be dispensable for the secretion of TssM. The C-terminal half
      of TssM, which contains Cys and His box motifs conserved in eukaryotic
      deubiquitinases, was purified and biochemically characterized. Recombinant TssM
      hydrolyzed multiple ubiquitinated substrates and the cysteine at position 102 was
      critical for enzymatic activity. The tssM gene was expressed within 1 h after
      uptake of B. mallei into RAW 264.7 murine macrophages, suggesting that the TssM
      deubiquitinase is produced in this intracellular niche. Although the
      physiological substrate(s) is currently unknown, the TssM deubiquitinase may
      provide B. mallei a selective advantage in the intracellular environment during
      infection.

PMID- 19168748
TI  - The linear form of a group II intron catalyzes efficient autocatalytic reverse
      splicing, establishing a potential for mobility.
AB  - Self-splicing group II introns catalyze their own excision from pre-RNAs, thereby
      joining the flanking exons. The introns can be released in a lariat or linear
      form. Lariat introns have been shown to reverse the splicing reaction; in
      contrast, linear introns are generally believed to perform no or only poor
      reverse splicing. Here, we show that a linear group II intron derived from
      ai5gamma can reverse the second step of splicing with unexpectedly high
      efficiency and precision. Moreover, the linear intron generates dramatically more
      reverse-splicing product than its lariat equivalent. The finding that linear
      group II introns can readily undergo the critical first step of mobility by
      catalyzing efficient reverse splicing into complementary target molecules
      demonstrates their innate potential for mobility and transposition and raises the
      possibility that reverse splicing by linear group II introns may have played a
      significant role in certain forms of intron mobility and lateral gene transfer
      during evolution.

PMID- 19168749
TI  - Investigating the specificity and stoichiometry of RNA binding by the
      nucleocapsid protein of Bunyamwera virus.
AB  - Bunyamwera virus (BUNV) is the prototypic member of both the Orthobunyavirus
      genus and the Bunyaviridae family of negative stranded RNA viruses. In common
      with all negative stranded RNA viruses, the BUNV genomic and anti-genomic strands
      are not naked RNAs, but instead are encapsidated along their entire lengths with
      the virus-encoded nucleocapsid (N) protein to form a ribonucleoprotein (RNP)
      complex. This association is critical for the negative strand RNA virus life
      cycle because only RNPs are active for productive RNA synthesis and RNA
      packaging. We are interested in understanding the molecular details of how N and
      RNA components associate within the bunyavirus RNP, and what governs the
      apparently selective encapsidation of viral replication products. Toward this
      goal, we recently devised a protocol that allowed generation of native BUNV N
      protein that maintained solubility under physiological conditions and allowed
      formation of crystals that yielded high-resolution x-ray diffraction data. Here
      we extend this work to show that this soluble N protein is able to oligomerize
      and bind RNA to form a highly uniform RNP complex, which exhibits characteristics
      in common with the viral RNP. By extracting and sequencing RNAs bound to these
      model RNPs, we determined the stoichiometry of N-RNA association to be
      approximately 12 nucleotides per N monomer. In addition, we defined the minimal
      sequence requirement for BUNV RNA replication. By comparing this minimal sequence
      to those bound to our model RNP, we conclude that N protein does not obligatorily
      require a sequence or structure for RNA encapsidation.

PMID- 19168750
TI  - Why the International Workshops on Opportunistic Protists?

PMID- 19168752
TI  - Overview of the presentations on microsporidia and free-living amebae at the 10th
      International Workshops on Opportunistic Protists.

PMID- 19168751
TI  - Pneumocystis workshop: 10th anniversary summary.

PMID- 19168753
TI  - Overview of Cryptosporidium presentations at the 10th International Workshops on
      Opportunistic Protists.

PMID- 19168754
TI  - Polymorphic mucin antigens CpMuc4 and CpMuc5 are integral to Cryptosporidium
      parvum infection in vitro.
AB  - Cryptosporidium, a waterborne enteric parasite, is a frequent cause of diarrheal
      disease outbreaks worldwide. Thus far, the few antigens shown to be important for
      attachment to and invasion of the host cell by Cryptosporidium are all mucin-like
      glycoproteins. In order to investigate other antigens that could be important for
      Cryptosporidium host-parasite interactions, the Cryptosporidium genome databases
      were mined for other mucin-like genes. A single locus of seven small mucin
      sequences was identified on chromosome 2 (CpMuc1 to -7). Reverse transcriptase
      PCR analysis demonstrated that all seven CpMucs were expressed throughout
      intracellular development. CpMuc4 and CpMuc5 were selected for further
      investigation because of the significant sequence divergence between
      Cryptosporidium parvum and C. hominis alleles. Rabbit anti-CpMuc5 and -CpMuc4
      antibodies identified several polypeptides in C. parvum lysates, suggestive of
      proteolytic processing of the mucins. All polypeptides were larger than the
      predicted molecular weight, which is suggestive of posttranslational processing,
      most likely O-glycosylation. In immunofluorescence assays, both anti-CpMuc4 and 
      CpMuc5 antibodies reacted with the apical region of sporozoites and revealed
      surface-exposed epitopes. The antigens were not shed during excystation but did
      partition into the aqueous phase of Triton X-114 extractions. Consistent with a
      role in attachment and invasion, CpMuc4 and CpMuc5 could be detected binding to
      fixed Caco-2A cells, and anti-CpMuc4 peptide antibodies inhibited Cryptosporidium
      infection in vitro. Sequencing of CpMuc4 and CpMuc5 from C. hominis clinical
      isolates identified several polymorphic alleles. The data suggest that these
      antigens are integral for Cryptosporidium infection in vitro and may be potential
      vaccine candidates.

PMID- 19168755
TI  - Dual sorting of the Saccharomyces cerevisiae vacuolar protein Sna4p.
AB  - Sna4p, a vacuolar membrane protein, belongs to a small family of proteins
      conserved in plants and fungi. It is transported to the vacuolar membrane via the
      alkaline phosphatase (ALP) pathway, which bypasses the multivesicular bodies
      (MVBs). Here, we show that transfer of Sna4p by the ALP route involves the AP-3
      adaptor protein complex, which binds to an acidic dileucine sorting signal in the
      cytoplasmic region of Sna4p. In addition, Sna4p can use the MVB pathway by using
      a PPPY motif, which is involved in the interaction with ubiquitin ligase Rsp5p.
      Deletion or mutation of the Sna4p PPPY motif or a low level of Rsp5p inhibits the
      entrance of Sna4p into MVBs. Sna4p is polyubiquitylated on its only lysine, and
      Sna4p lacking this lysine shows defective MVB sorting. These data indicate that
      Sna4p has two functional motifs, one for interaction with the AP-3 complex,
      followed by entry into the ALP pathway, and one for binding Rsp5p, which directs
      the protein to the MVB pathway. The presence of these two motifs allows Sna4p to
      localize to both the vacuolar membrane and the lumen.

PMID- 19168756
TI  - Toxoplasma gondii presentations at the 10th International Workshops on
      Opportunistic Protists: 100 years and counting.

PMID- 19168757
TI  - AgtA, the dicarboxylic amino acid transporter of Aspergillus nidulans, is
      concertedly down-regulated by exquisite sensitivity to nitrogen metabolite
      repression and ammonium-elicited endocytosis.
AB  - We identified agtA, a gene that encodes the specific dicarboxylic amino acid
      transporter of Aspergillus nidulans. The deletion of the gene resulted in loss of
      utilization of aspartate as a nitrogen source and of aspartate uptake, while not
      completely abolishing glutamate utilization. Kinetic constants showed that AgtA
      is a high-affinity dicarboxylic amino acid transporter and are in agreement with
      those determined for a cognate transporter activity identified previously. The
      gene is extremely sensitive to nitrogen metabolite repression, depends on AreA
      for its expression, and is seemingly independent from specific induction. We
      showed that the localization of AgtA in the plasma membrane necessitates the ShrA
      protein and that an active process elicited by ammonium results in
      internalization and targeting of AgtA to the vacuole, followed by degradation.
      Thus, nitrogen metabolite repression and ammonium-promoted vacuolar degradation
      act in concert to downregulate dicarboxylic amino acid transport activity.

PMID- 19168758
TI  - 90-kilodalton heat shock protein, Hsp90, as a target for genotyping
      Cryptosporidium spp. known to infect humans.
AB  - Small-subunit (SSU) rRNA-based methods have been commonly used in the
      differentiation of Cryptosporidium species or genotypes. In order to develop a
      new tool for confirming the genotypes of Cryptosporidium species, parts of the 90
      kDa heat shock protein (Hsp90) genes of seven Cryptosporidium species and
      genotypes known to infect humans (C. hominis, C. parvum, C. meleagridis, C.
      canis, C. muris, C. suis, and the cervine genotype), together with one from
      cattle (C. andersoni), were sequenced and analyzed. With the exception of C.
      felis from cats and C. baileyi from birds, the Hsp90 genes of all tested
      Cryptosporidium species were amplified. Phylogenetic analysis of the hsp90
      sequences from all these species is congruent with previous studies in which the
      SSU rRNA, 70-kDa heat shock protein, oocyst wall protein, and actin genes were
      analyzed and showed that gastric and intestinal parasites segregate into two
      distinct clades. In this study, the secondary products of hsp90 produced after
      PCR-restriction fragment length digestion with StyI and HphI or with BbsI showed
      that parasites within the intestinal or gastric clade could be differentiated
      from each other. These data confirm the utility of the Hsp90 gene as a sensitive,
      specific, and robust molecular tool for differentiating species and/or genotypes
      of Cryptosporidium in clinical specimens.

PMID- 19168759
TI  - Towards new antifolates targeting eukaryotic opportunistic infections.
AB  - Trimethoprim, an antifolate commonly prescribed in combination with
      sulfamethoxazole, potently inhibits several prokaryotic species of dihydrofolate
      reductase (DHFR). However, several eukaryotic pathogenic organisms are resistant
      to trimethoprim, preventing its effective use as a therapeutic for those
      infections. We have been building a program to reengineer trimethoprim to more
      potently and selectively inhibit eukaryotic species of DHFR as a viable strategy
      for new drug discovery targeting several opportunistic pathogens. We have
      developed a series of compounds that exhibit potent and selective inhibition of
      DHFR from the parasitic protozoa Cryptosporidium and Toxoplasma as well as the
      fungus Candida glabrata. A comparison of the structures of DHFR from the fungal
      species Candida glabrata and Pneumocystis suggests that the compounds may also
      potently inhibit Pneumocystis DHFR.

PMID- 19168761
TI  - Pancreas: peritoneal reflections, ligamentous connections, and pathways of
      disease spread.
AB  - The pancreas is a retroperitoneal organ with a close anatomic relationship to the
      peritoneal reflections in the abdomen, including the transverse mesocolon and the
      small bowel mesentery, and is directly contiguous to peritoneal ligaments such as
      the hepatoduodenal ligament, gastrohepatic ligament, splenorenal ligament,
      gastrocolic ligament, and the greater omentum. Understanding of these anatomic
      relationships of the pancreas is aided by knowledge of its embryologic
      development. These reflections and ligaments are potential pathways for spread of
      disease processes such as pancreatitis and pancreatic carcinoma. One can
      recognize these ligaments and reflections by identifying the blood vessels that
      traverse them.

PMID- 19168760
TI  - Role of CpSUB1, a subtilisin-like protease, in Cryptosporidium parvum infection
      in vitro.
AB  - The apicomplexan parasite Cryptosporidium is a significant cause of diarrheal
      disease worldwide. Previously, we reported that a Cryptosporidium parvum
      subtilisin-like serine protease activity with furin-type specificity cleaves
      gp40/15, a glycoprotein that is proteolytically processed into gp40 and gp15,
      which are implicated in mediating infection of host cells. Neither the enzyme(s)
      responsible for the protease activity in C. parvum lysates nor those that process
      gp40/15 are known. There are no furin or other proprotein convertase genes in the
      C. parvum genome. However, a gene encoding CpSUB1, a subtilisin-like serine
      protease, is present. In this study, we cloned the CpSUB1 genomic sequence and
      expressed and purified the recombinant prodomain. Reverse transcriptase PCR
      analysis of RNA from C. parvum-infected HCT-8 cells revealed that CpSUB1 is
      expressed throughout infection in vitro. In immunoblots, antiserum to the
      recombinant CpSUB1 prodomain revealed two major bands, of approximately 64 kDa
      and approximately 48 kDa, for C. parvum lysates and proteins "shed" during
      excystation. In immunofluorescence assays, the antiserum reacted with the apical
      region of sporozoites and merozoites. The recombinant prodomain inhibited
      protease activity and processing of recombinant gp40/15 by C. parvum lysates but
      not by furin. Since prodomains are often selective inhibitors of their cognate
      enzymes, these results suggest that CpSUB1 may be a likely candidate for the
      protease activity in C. parvum and for processing of gp40/15. Importantly, the
      recombinant prodomain inhibited C. parvum infection of HCT-8 cells. These studies
      indicate that CpSUB1 plays a significant role in infection of host cells by the
      parasite and suggest that this enzyme may serve as a target for intervention.

PMID- 19168762
TI  - Strategies for establishing a comprehensive quality and performance improvement
      program in a radiology department.
AB  - To improve the safety and quality of the care that radiologists provide, and to
      allow radiologists and radiology personnel to remain competitive in an
      increasingly complex environment, it is essential that all imaging departments
      establish and maintain managed, comprehensive, and effective performance
      improvement programs. Although the structure and focus of these programs can
      vary, a number of common components exist, many of which are now widely mandated
      by organizations that regulate the field of radiology. Basic components include
      patient safety, process improvement, customer service, professional staff
      assessment, and education, each of which requires strategies for implementing
      continuous programs to monitor performance, analyzing and depicting data,
      implementing change, and meeting regulatory requirements. All of these components
      are part of a comprehensive quality management system in a large academic
      radiology department. For smaller departments or practices, the gradual
      introduction of one or more of these components is useful in ensuring the safety
      and quality of their services.

PMID- 19168764
TI  - Ultrasound biosafety considerations for the practicing sonographer and
      sonologist.
AB  - The purpose of this article is to present the practicing sonographer and
      sonologist with an overview of the biohazards of ultrasound and guidelines for
      safe use.

PMID- 19168763
TI  - Problem-centric organization and visualization of patient imaging and clinical
      data.
AB  - A patient's electronic medical record contains a large amount of unstructured
      textual information. As patient records become increasingly dense owing to an
      aging population and increased occurrence of chronic diseases, a tool is needed
      to help organize and navigate patient data in a way that facilitates a
      clinician's ability to understand this information and that improves efficiency.
      A system has been developed for physicians that summarizes clinical information
      from a patient record. This system provides a gestalt view of the patient's
      record by organizing information about each disease along four dimensions (axes):
      time (eg, disease progression over time), space (eg, tumor in left frontal lobe),
      existence (eg, certainty of existence of a finding), and causality (eg, response
      to treatment). A display is generated from information provided by radiology
      reports and discharge summaries. Natural language processing is used to identify
      clinical abnormalities (problems, symptoms, findings) from these reports as well
      as associated properties and relationships. This information is presented in an
      integrated format that organizes extracted findings into a problem list, depicts
      the information on a timeline grid, and provides direct access to relevant
      reports and images. The goal of this system is to improve the structure of
      clinical information and its presentation to the physician, thereby simplifying
      the information retrieval and knowledge discovery necessary to bridge the gap
      between acquiring raw data and making an informed diagnosis.

PMID- 19168765
TI  - Evaluation of the accuracy of 3-dimensional ultrasonography of the kidney using
      an in vitro renal model.
AB  - OBJECTIVE: Three-dimensional ultrasonography (3DUS) has recently become a reality
      because of advances in ultrasound probes and machine processing ability. We have
      developed an anthropomorphic phantom of the human loin to assess both the
      accuracy of 3DUS of the kidney and its potential usefulness for training in
      ultrasonographically guided percutaneous renal intervention. METHODS: The model
      was built with easily available and inexpensive materials such as agar and latex
      with known ultrasonographic properties. The accuracy of 2-dimensional
      ultrasonography (2DUS) and 3DUS was assessed by measuring the dimensions of the
      pelvicalyceal system (PCS) ultrasonographically (pelvis width and calyx
      diameters) and then comparing these with measurements obtained at the time of
      construction. Radiology interventional trainees then punctured the PCS with 2DUS
      and 4-dimensional ultrasonographic (real-time/time-resolved 3DUS) guidance and
      reported the phantom's performance. RESULTS: The 3-dimensional nature of the
      model's PCS could be clearly visualized on 2DUS and 3DUS, and the scan
      characteristics were very similar to those in real life. Measurements using 3DUS
      proved to be closer to the true dimensions of the model's PCS than those using
      2DUS. The mean error percentage for 2DUS measurements was -10.2%, and that for
      3DUS was -2.2% (P < 0.0001). Interventional trainees were satisfied with the
      "tissue feel" and level of difficulty posed on puncturing the phantom.
      CONCLUSIONS: Three-dimensional ultrasonography proved to be more accurate than
      2DUS for intrarenal measurements using this in vitro renal model. Three
      dimensional ultrasonography has the potential to ease diagnostic renal scanning
      with the ability to further scrutinize and postprocess the scanned volumes. The
      model was realistic in its anthropomorphic properties and simulated human tissue
      during puncture.

PMID- 19168766
TI  - Sonographic interstitial syndrome: the sound of lung water.
AB  - OBJECTIVE: Ultrasound lung comets (ULCs) now have an acknowledged correlation
      with extravascular lung water, but they present in different orders and numbers
      in different pathologic pulmonary entities. How these artifacts are created is
      not yet known, and the literature gives discordant hypotheses. Understanding
      their formation is the first step in understanding lung disease. The purpose of
      this study was to show the morphologic and genetic variability of interstitial
      lung disease studied with echography and thus to propose a unitary mechanism for
      the formation of ULCs. METHODS: This study included 3 parts: (1) a retrospective
      analysis of echographic lung images of patients with interstitial syndrome; (2)
      an analysis of the literature for definitions of the size of the pulmonary
      lobule; and (3) an experimental model of different air-water interfaces scanned
      with varying ultrasonic frequencies. RESULTS: The retrospective analysis of
      echographic lung images included 176 patients with diffuse ULCs: 118 patients had
      acute pulmonary edema; 18 had acute lung injury/acute respiratory distress
      syndrome; and 40 were premature neonates with respiratory distress syndrome.
      Experimental models permitted us to discover that ring-down artifacts are
      produced only by single and double layers of bubbles in specific structural
      settings. CONCLUSIONS: Reverberation between bubbles with a critical radius seems
      to be at the origin of ring-down artifacts. Echographic manifestations of
      interstitial lung disease, whose genesis lies in the partial air loss of lobes
      and segments, are acoustic phenomena originating from variations in the tissue
      fluid relationship of the lung. A correlation between anatomopathologic
      characteristics and structures of sonographic artifacts could allow more rapid
      and noninvasive diagnoses.

PMID- 19168767
TI  - Increase in the late diastolic filling force is associated with impaired
      transmitral flow efficiency in acute moderate elevation of left ventricular
      afterload.
AB  - OBJECTIVE: Analysis of intraventricular flow force and efficiency is a novel
      concept of quantitatively assessing left ventricular (LV) hemodynamic
      performance. We have parametrically characterized diastolic filling flow by early
      inflow force, late inflow force, and total inflow force and by vortex formation
      time (VFT), a fundamental parameter of fluid transport efficiency. The purpose of
      this study was to determine what changes in inflow forces characterize a decrease
      in diastolic blood transport efficiency in acute moderate elevation of LV
      afterload. METHODS: In 8 open-chested pigs, the flow force and VFT parameters
      were calculated from conventional and flow Doppler echocardiographic measurements
      at baseline and during a brief (3-minute) moderate elevation of afterload induced
      by increasing the systolic blood pressure to 130% of the baseline value. RESULTS:
      Systolic LV function decreased significantly during elevated afterload. Early
      inflow force did not significantly change, whereas late inflow force increased
      from 5,822.09 +/- 1,656.5 (mean +/- SD) to 13,948.25 +/- 9,773.96 dyne (P =
      .049), and total inflow force increased from 13,783.35 +/- 4,816.58 to 21,836.67
      +/- 8,635.33 dyne (P = .031). Vortex formation time decreased from 4.09 +/- 0.29
      to 2.79 +/- 1.1 (P = .0068), confirming suboptimal flow transport efficiency.
      CONCLUSIONS: Even a brief moderate increase of LV afterload causes a significant
      increase in late diastolic filling force and impairs transmitral flow efficiency.

PMID- 19168768
TI  - Localization of parathyroid adenomas by sonography and technetium tc 99m
      sestamibi single-photon emission computed tomography before minimally invasive
      parathyroidectomy: are both studies really needed?
AB  - OBJECTIVE: The purpose of this study was to determine the utility of radiologist
      performed sonography as the principal modality for parathyroid localization
      before minimally invasive parathyroidectomy. METHODS: Both sonography and
      technetium Tc 99m sestamibi single-photon emission computed tomography (SPECT)
      are commonly performed during imaging evaluation of patients with primary
      hyperparathyroidism (HPTH). Sonographic examinations ordered during the study
      period were performed by 1 author (M.E.T.), and results were immediately
      reported. Findings of a subsequent Tc 99m sestamibi study were recorded blinded
      to the sonographic results. The sensitivity and specificity of sonography and Tc
      99m sestamibi SPECT were assessed with the use of surgery and pathology reports
      as a reference standard. The 2007 global Medicare reimbursement rates were used
      to assess the costs of preoperative localization. RESULTS: Parathyroidectomy was
      performed in 144 of 172 patients evaluated by both modalities. The sensitivity,
      specificity, and positive predictive value of sonography for identifying abnormal
      parathyroid glands were 74%, 96%, and 90%, respectively. Sonography correctly
      localized a single adenoma or suggested multiglandular disease in 112 of 144
      patients (78%). The sensitivity, specificity, and positive predictive value of
      SPECT were 58%, 96%, and 89%. Technetium 99m sestamibi SPECT correctly predicted
      an adenoma or multiglandular disease in 88 of 144 patients (61%). Five patients
      with negative sonographic findings were shown to have uniglandular disease on Tc
      99m sestamibi SPECT. Selective use of Tc 99m sestamibi SPECT (ie, when
      sonographic findings were negative or equivocal) would have decreased the cost of
      imaging by 53%. CONCLUSIONS: Radiologist-performed sonography may potentially be
      used as a principal imaging modality for patients with HPTH. Selective use of Tc
      99m sestamibi in cases with negative or equivocal sonographic findings can
      decrease the cost of imaging before parathyroid resection considerably.

PMID- 19168769
TI  - An intraoperative brain shift monitor using shear mode transcranial ultrasound:
      preliminary results.
AB  - OBJECTIVE: Various methods of intraoperative structural monitoring during
      neurosurgery are used to localize lesions after brain shift and to guide
      surgically introduced probes such as biopsy needles or stimulation electrodes.
      With its high temporal resolution, portability, and nonionizing mode of
      radiation, ultrasound has potential advantages over other existing imaging
      modalities for intraoperative monitoring, yet ultrasound is rarely used during
      neurosurgery largely because of the craniotomy requirement to achieve
      sufficiently useful signals. METHODS: Prompted by results from recent studies on
      transcranial ultrasound, a prototype device that aims to use the shear mode of
      transcranial ultrasound transmission for intraoperative monitoring was designed,
      constructed, and tested with 10 human participants. Magnetic resonance images
      were then obtained with the device spatially registered to the magnetic resonance
      imaging (MRI) reference coordinates. Peaks in both the ultrasound and MRI signals
      were identified and analyzed for both spatial localization and signal-to-noise
      ratio (SNR). RESULTS: The first results aimed toward validating the prototype
      device with MRI showed an excellent correlation (n = 38; R(2) = 0.9962) between
      the structural localization abilities of the two modalities. In addition, the
      overall SNR of the ultrasound backscatter signals (n = 38; SNR = 25.4 +/- 5.2 dB,
      mean +/- SD) was statistically equivalent to that of the MRI data (n = 38; SNR =
      22.5 +/- 4.8 dB). CONCLUSIONS: A statistically significant correlation of
      localized intracranial structures between intraoperative transcranial ultrasound
      monitoring and MRI data was achieved with 10 human participants. We have shown
      and validated a prototype device incorporating transcranial shear mode ultrasound
      for clinical monitoring applications.

PMID- 19168770
TI  - Experimental studies with a 9F forward-looking intracardiac imaging and ablation
      catheter.
AB  - OBJECTIVE: The purpose of this study was to develop a high-resolution, near-field
      optimized 14-MHz, 24-element broad-bandwidth forward-looking array for
      integration on a steerable 9F electrophysiology (EP) catheter. METHODS: Several
      generations of prototype imaging catheters with bidirectional steering, termed
      microlinear (ML), were built and tested as integrated catheter designs with EP
      sensing electrodes near the tip. The wide-bandwidth ultrasound array was mounted
      on the very tip, equipped with an aperture of only 1.2 by 1.58 mm. The array
      pulse echo performance was fully simulated, and its construction offered
      shielding from ablation noise. Both ex vivo and in vivo imaging with a porcine
      animal model were performed. RESULTS: The array pulse echo performance was
      concordant with Krimholtz-Leedom-Matthaei model simulation. Three generations of
      prototype devices were tested in the right atrium and ventricle in 4 acute pig
      studies for the following characteristics: (1) image quality, (2) anatomic
      identification, (3) visualization of other catheter devices, and (4) for a
      mechanism for stabilization when imaging ablation. The ML catheter is capable of
      both low-artifact ablation imaging on a standard clinical imaging system and high
      frame rate myocardial wall strain rate imaging for detecting changes in cardiac
      mechanics associated with ablation. CONCLUSIONS: The imaging resolution
      performance of this very small array device, together with its penetration beyond
      2 cm, is excellent considering its very small array aperture. The forward-looking
      intracardiac catheter has been adapted to work easily on an existing commercial
      imaging platform with very minor software modifications.

PMID- 19168771
TI  - New sonographic aspects of peyronie disease.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of sonography in the
      identification of several types of lesions seen in patients with Peyronie disease
      (PD). METHODS: A total of 78 patients were examined. Penile lesions were counted,
      classified, and categorized according to their anatomic location and sonographic
      presentation. RESULTS: The classic sonographic presentation, as well as less
      common and novel findings, are described and correlated with clinically relevant
      data and physical examination findings. CONCLUSIONS: Sonography can precisely
      assess the size and location of the plaques found in PD and can also aid in
      treatment.

PMID- 19168772
TI  - Thrombosed pseudoaneurysm of the breast after blunt trauma.

PMID- 19168773
TI  - Urgent carotid endarterectomy: the role of serial ultrasound studies in early
      detection of plaque rupture.

PMID- 19168774
TI  - Sonographic appearance of a retained tunneled catheter cuff causing a foreign
      body reaction.

PMID- 19168775
TI  - Pseudoaneurysm of the mitral-aortic intervalvular fibrosa in a patient after
      radio frequency catheter ablation of atrial fibrillation.

PMID- 19168776
TI  - Sonographic findings of physiologic left brachiocephalic vein compression in a
      case initially misdiagnosed as a left internal jugular vein thrombus.

PMID- 19168777
TI  - The vaginal ring: expelled or misplaced?

PMID- 19168778
TI  - Fibrous capsular contracture of a testicular implant.

PMID- 19168779
TI  - Riedel thyroiditis associated with massive neck fibrosis.

PMID- 19168780
TI  - Sonographic appearance of metallic ureteric stents.

PMID- 19168781
TI  - Body adiposity in late life and risk of dementia or cognitive impairment in a
      longitudinal community-based study.
AB  - BACKGROUND: The association between body adiposity at older ages and the
      development of cognitive impairment is unclear. METHODS: The association of body
      mass index (BMI) and waist circumference in late life with incidence of cognitive
      impairment was prospectively examined in a cohort study of 1,351 Latinos, aged 60
      101 and residents of the Sacramento, CA, area at study baseline. The status of
      dementia and "cognitive impairment but not demented" (CIND) was determined at
      baseline and at each of five follow-up examinations by a multistage assessment
      protocol. Incident cases of dementia and CIND were combined (dementia/CIND) for
      more than 8 years of follow-up. BMI was categorized as less than 25.0, 25.0-29.9
      (overweight), and 30 kg/m(2) or greater (obese). Waist circumference was
      categorized into sex-specific tertiles. RESULTS: Dementia/CIND was diagnosed in
      110 (8.2%) participants. Compared with the lowest BMI category, overweight
      participants had a 48% decreased rate of dementia/CIND (adjusted hazard ratio
      [HR] = 0.52, 95% confidence interval [CI]: 0.30-0.91) and obese participants had
      a 61% decreased rate of dementia/CIND (HR = 0.39, 95% CI: 0.20-0.78). Rates of
      dementia/CIND for the middle and high tertile of waist circumference, compared
      with the low tertile, were 80% and 90% higher, respectively (adjusted HR = 1.8,
      95% CI: 1.1-3.1, and adjusted HR = 1.9, 95% CI: 0.91-3.8). CONCLUSIONS: Abdominal
      fat in late life appears to confer an increased risk for dementia/CIND, whereas
      overall obesity appears to be protective. This may reflect age-related changes in
      body composition and the association of visceral fat with metabolic
      dysregulation.

PMID- 19168783
TI  - The structure of the ankyrin-binding site of beta-spectrin reveals how tandem
      spectrin-repeats generate unique ligand-binding properties.
AB  - Spectrin and ankyrin participate in membrane organization, stability, signal
      transduction, and protein targeting; their interaction is critical for
      erythrocyte stability. Repeats 14 and 15 of betaI-spectrin are crucial for
      ankyrin recognition, yet the way spectrin binds ankyrin while preserving its
      repeat structure is unknown. We have solved the crystal structure of the betaI
      spectrin 14,15 di-repeat unit to 2.1 A resolution and found 14 residues critical
      for ankyrin binding that map to the end of the helix C of repeat 14, the linker
      region, and the B-C loop of repeat 15. The tilt (64 degrees) across the 14,15
      linker is greater than in any published di-repeat structure, suggesting that the
      relative positioning of the two repeats is important for ankyrin binding. We
      propose that a lack of structural constraints on linker and inter-helix loops
      allows proteins containing spectrin-like di-repeats to evolve diverse but
      specific ligand-recognition sites without compromising the structure of the
      repeat unit. The linker regions between repeats are thus critical determinants of
      both spectrin's flexibility and polyfunctionality. The putative coupling of
      flexibility and ligand binding suggests a mechanism by which spectrin might
      participate in mechanosensory regulation.

PMID- 19168782
TI  - Genetic epidemiology in aging research.
AB  - Over the last two decades, aging research has expanded to include not only age
      related disease models, and conversely, longevity and disease-free models, but
      also focuses on biological mechanisms related to the aging process. By viewing
      aging on multiple research frontiers, we are rapidly expanding knowledge as a
      whole and mapping connections between biological processes and particular age
      related diseases that emerge. This is perhaps most true in the field of genetics,
      where variation across individuals has improved our understanding of aging
      mechanisms, etiology of age-related disease, and prediction of therapeutic
      responses. A close partnership between gerontologists, epidemiologists, and
      geneticists is needed to take full advantage of emerging genome information and
      technology and bring about a new age for biological aging research. Here we
      review current genetic findings for aging across both disease-specific and aging
      process domains. We then highlight the limitations of most work to date in terms
      of study design, genomic information, and trait modeling and focus on emerging
      technology and future directions that can partner genetic epidemiology and aging
      research fields to best take advantage of the rapid discoveries in each.

PMID- 19168784
TI  - Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation
      strategy in mantle cell lymphoma.
AB  - In this study, we analyzed the long-term outcome of a risk-adapted
      transplantation strategy for mantle cell lymphoma in 121 patients enrolled in
      sequential transplantation protocols. Notable developments over the 17-year study
      period were the addition of rituximab to chemotherapy and preparative regimens
      and the advent of nonmyeloablative allogeneic stem cell transplantation (NST). In
      the autologous transplantation group (n = 86), rituximab resulted in a marked
      improvement in progression-free survival for patients who received a transplant
      in their first remission (where a plateau emerged at 3-8 years) but did not
      change the outcomes for patients who received a transplant beyond their first
      remission. In the NST group, composed entirely of patients who received a
      transplant beyond their first remission, durable remissions also emerged in
      progression-free survival at 5 to 9 years. The major determinants of disease
      control after NST were the use of a peripheral blood stem cell graft and donor
      chimerism of at least 95%, whereas the major determinant of death was
      immunosuppression for chronic graft-versus-host disease. Our results show that
      long-term disease-free survival in mantle cell lymphoma is possible after
      rituximab-containing autologous transplantation for patients in first remission
      and after NST for patients with relapsed or refractory disease.

PMID- 19168785
TI  - Distinct roles of stress-activated protein kinases in Fanconi anemia-type C
      deficient hematopoiesis.
AB  - The underlying molecular mechanisms that promote bone marrow failure in Fanconi
      anemia are incompletely understood. Evidence suggests that enhanced apoptosis of
      hematopoietic precursors is a major contributing factor. Previously, enhanced
      apoptosis of Fanconi anemia type C-deficient (Fancc(-/-)) progenitors was shown
      to involve aberrant p38 MAPK activation. Given the importance of c-Jun N-terminal
      kinase (JNK) in the stress response, we tested whether enhanced apoptosis of
      Fancc(-/-) cells also involved altered JNK activation. In Fancc(-/-) murine
      embryonic fibroblasts, tumor necrosis factor alpha (TNF-alpha) induced elevated
      JNK activity. In addition, JNK inhibition protected Fancc(-/-) murine embryonic
      fibroblasts and c-kit(+) bone marrow cells from TNF-alpha-induced apoptosis.
      Importantly, hematopoietic progenitor assays demonstrated that JNK inhibition
      enhanced Fancc(-/-) colony formation in the presence of TNF-alpha. Competitive
      repopulation assays showed that Fancc(-/-) donor cells cultured with the JNK
      inhibitor had equivalent levels of donor chimerism compared with Fancc(-/-) donor
      cells cultured with vehicle control. In contrast, culturing Fancc(-/-) cells with
      a p38 MAPK inhibitor significantly increased repopulating ability, supporting an
      integral role of p38 MAPK in maintaining Fancc(-/-) hematopoietic stem cell
      function. Taken together, these data suggest that p38 MAPK, but not JNK, has a
      critical role in maintaining the engraftment of Fancc(-/-)-reconstituting cells
      under conditions of stress.

PMID- 19168786
TI  - Caspase-7 deficiency protects from endotoxin-induced lymphocyte apoptosis and
      improves survival.
AB  - Extensive apoptosis of leukocytes during sepsis and endotoxic shock constitutes
      an important mechanism linked to the excessive mortality associated with these
      disorders. Caspase inhibitors confer protection from endotoxin-induced lymphocyte
      apoptosis and improve survival, but it is not clear which caspases mediate
      lipopolysaccharide (LPS)-induced lymphocyte apoptosis and mortality. We report
      here that the apoptotic executioner caspase-7 was activated in the splenocytes of
      LPS-injected mice, suggesting a role for caspase-7 in lymphocyte apoptosis.
      Indeed, caspase-7-deficient mice were resistant to LPS-induced lymphocyte
      apoptosis and were markedly protected from LPS-induced lethality independently of
      the excessive production of serum cytokines. These results reveal for the first
      time a nonredundant role for caspase-7 in vivo and identify caspase-7 inhibition
      as a component of the mechanism by which caspase inhibitors protect from
      endotoxin-induced mortality.

PMID- 19168787
TI  - Long-term outcome after hematopoietic stem cell transplantation of a single
      center cohort of 90 patients with severe combined immunodeficiency.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment
      for severe combined immunodeficiency (SCID). Detailed assessment of the long-term
      outcome of HSCT, ie, the occurrence of clinical events and the quality and
      stability of immune reconstitution, is now required. We performed a single-center
      retrospective analysis of the long-term outcome of HSCT in 90-patient cohort
      followed for between 2 and 34 years (median, 14 years). Clinical events and
      immune reconstitution data were collected. Almost half the patients have
      experienced one or more significant clinical events, including persistent chronic
      graft-versus-host disease (GVHD), autoimmune and inflammatory manifestations,
      opportunistic and nonopportunistic infections, chronic human papilloma virus
      (HPV) infections, and a requirement for nutritional support. With the notable
      exception of severe HPV infection, these complications tend to become less common
      15 years later after HSCT. A multivariate analysis showed that the occurrence of
      these events correlated with non-genoidentical donors, diagnosis of Artemis SCID,
      and quality of immune reconstitution. In most cases, HSCT enables long-term
      survival with infrequent sequelae. However, the occurrence of relatively late
      onset complications is a concern that requires specific means of prevention and
      justifies careful patient follow-up.

PMID- 19168788
TI  - Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host
      disease.
AB  - Chronic graft-versus-host disease (cGVHD) causes significant morbidity and
      mortality in patients otherwise cured of malignancy after hematopoietic stem cell
      transplantation (HSCT). The presence of alloantibodies and high plasma B cell
      activating factor (BAFF) levels in patients with cGVHD suggest that B cells play
      a role in disease pathogenesis. We performed detailed phenotypic and functional
      analyses of peripheral B cells in 82 patients after HSCT. Patients with cGVHD had
      significantly higher BAFF/B-cell ratios compared with patients without cGVHD or
      healthy donors. In cGVHD, increasing BAFF concentrations correlated with
      increased numbers of circulating pre-germinal center (GC) B cells and post-GC
      "plasmablast-like" cells, suggesting in vivo BAFF dependence of these 2 CD27(+) B
      cell subsets. Circulating CD27(+) B cells in cGVHD comprised in vivo activated B
      cells capable of IgG production without requiring additional antigen stimulation.
      Serial studies revealed that patients who subsequently developed cGVHD had
      delayed reconstitution of naive B cells despite persistent BAFF elevation as well
      as proportional increase in CD27(+) B cells in the first year after HSCT. These
      studies delineate specific abnormalities of B-cell homeostasis in patients with
      cGVHD and suggest that BAFF targeting agents may be useful in this disease.

PMID- 19168789
TI  - Limited ability of humoral immune responses in control of viremia during
      infection with SIVsmmD215 strain.
AB  - We investigated the impact of rhesus macaque (RM) B-cell depletion before
      inoculation with the isolate SIVsmmD215. Seven RMs were treated every 3 weeks
      with 50 mg/kg of an anti-CD20 antibody (rituximab) starting 7 days before
      inoculation for 2 (n = 4) and 5 (n = 3) months. Four control animals received no
      antibody. Three animals were completely depleted of CD20(+) B cells, but 4 were
      only partially depleted of CD20 cells in the LNs and intestine. The decrease in
      antibody production was consistent with the efficacy of tissue CD20 depletion.
      Seroconversion and neutralizing antibody production was significantly delayed in
      animals showing complete tissue CD20 depletion and remained at low titers in all
      CD20-depleted RMs. Surprisingly, there was no significant difference in acute or
      chronic viral loads between CD20-depleted and control animal groups. There was a
      tendency for lower viral set points in CD20-depleted animals. At 6 weeks after
      inoculation, cellular immune responses were significantly stronger in CD20
      depleted animals than in controls. There was no significant difference in
      survival between CD20-depleted and control animals. Our data suggest that a
      deficiency of Ab responses did not markedly affect viral replication or disease
      progression and that they may be compensated by more robust cellular responses.

PMID- 19168790
TI  - ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to
      immortalize hematopoietic progenitor cells.
AB  - ETS2 and ERG are transcription factors, encoded on human chromosome 21 (Hsa21),
      that have been implicated in human cancer. People with Down syndrome (DS), who
      are trisomic for Hsa21, are predisposed to acute megakaryoblastic leukemia
      (AMKL). DS-AMKL blasts harbor a mutation in GATA1, which leads to loss of full
      length protein but expression of the GATA-1s isoform. To assess the consequences
      of ETS protein misexpression on megakaryopoiesis, we expressed ETS2, ERG, and the
      related protein FLI-1 in wild-type and Gata1 mutant murine fetal liver
      progenitors. These studies revealed that ETS2, ERG, and FLI-1 facilitated the
      expansion of megakaryocytes from wild-type, Gata1-knockdown, and Gata1s knockin
      progenitors, but none of the genes could overcome the differentiation block
      characteristic of the Gata1-knockdown megakaryocytes. Although overexpression of
      ETS proteins increased the proportion of CD41(+) cells generated from Gata1s
      knockin progenitors, their expression led to a significant reduction in the more
      mature CD42 fraction. Serial replating assays revealed that overexpression of ERG
      or FLI-1 immortalized Gata1-knockdown and Gata1s knockin, but not wild-type,
      fetal liver progenitors. Immortalization was accompanied by activation of the
      JAK/STAT pathway, commonly seen in megakaryocytic malignancies. These findings
      provide evidence for synergy between alterations in GATA-1 and overexpression of
      ETS proteins in aberrant megakaryopoiesis.

PMID- 19168791
TI  - Murine neonatal recent thymic emigrants are phenotypically and functionally
      distinct from adult recent thymic emigrants.
AB  - In contrast to adults, the murine neonatal CD4+ compartment contains a high
      frequency of recent thymic emigrants (RTEs). However, the functional capabilities
      of these cells in neonates are relatively unknown. Moreover, it has not been
      determined whether RTEs from neonates and adults are comparable. Here we have
      directly compared neonatal and adult CD4+ RTEs for the first time, using a
      transgenic mouse strain that allows for the identification and purification of
      RTEs. Our data demonstrate that RTEs from murine neonates and adults are
      phenotypically and functionally distinct. In particular, although the magnitude
      of RTEs cytokine responses from both age groups is dependent on the conditions of
      activation, neonatal RTEs always exhibited higher levels of effector Th1/Th2
      cytokine production than adult RTEs. In addition, neonatal, but not adult, RTEs
      showed early proliferation in response to stimulation with interleukin-7 alone.
      This was associated with faster kinetics of interleukin-7Ralpha down-regulation
      and higher levels of pSTAT5 in neonatal RTEs. These quantitative and qualitative
      differences in the neonatal and adult RTEs populations may at least partially
      explain the diverse responses that are elicited in vivo in neonates in response
      to different conditions of antigen exposure.

PMID- 19168792
TI  - Genome-wide epigenetic analysis delineates a biologically distinct immature acute
      leukemia with myeloid/T-lymphoid features.
AB  - Acute myeloid leukemia is a heterogeneous disease from the molecular and biologic
      standpoints, and even patients with a specific gene expression profile may
      present clinical and molecular heterogeneity. We studied the epigenetic profiles
      of a cohort of patients who shared a common gene expression profile but differed
      in that only half of them harbored mutations of the CEBPA locus, whereas the rest
      presented with silencing of this gene and coexpression of certain T-cell markers.
      DNA methylation studies revealed that these 2 groups of patients could be readily
      segregated in an unsupervised fashion based on their DNA methylation profiles
      alone. Furthermore, CEBPA silencing was associated with the presence of an
      aberrant DNA hypermethylation signature, which was not present in the CEBPA
      mutant group. This aberrant hypermethylation occurred more frequently at sites
      within CpG islands. CEBPA-silenced leukemias also displayed marked
      hypermethylation compared with normal CD34(+) hematopoietic cells, whereas CEBPA
      mutant cases showed only mild changes in DNA methylation compared with these
      normal progenitors. Biologically, CEBPA-silenced leukemias presented with a
      decreased response to myeloid growth factors in vitro.

PMID- 19168793
TI  - Increased T-bet+ cytotoxic effectors and type I interferon-mediated processes in
      chronic graft-versus-host disease of the oral mucosa.
AB  - Although chronic graft-versus-host disease (cGVHD) is a major long-term
      complication of allogeneic hematopoietic stem cell transplantation, little is
      known of its pathogenesis. We have systematically examined oral mucosa among
      cGVHD patients and determined that the clinical severity of oral cGVHD was
      correlated with apoptotic epithelial cells, often found adjacent to infiltrating
      effector-memory T cells expressing markers of cytotoxicity and type I cytokine
      polarization. Accumulation of T-bet(+) T-cell effectors was associated with both
      increased proliferation and the expression of the type I chemokine receptor
      CXCR3. Concurrently, in both infiltrating cells and keratinocytes, we observed
      increased expression of the CXCR3 ligand MIG (CXCL9) and interleukin-15 (IL-15),
      type I interferon (IFN)-inducible factors that support the migration, type I
      differentiation, and expansion of alloreactive effectors. In severely affected
      mucosa, we observed high levels of MxA, a protein specifically induced by type I
      IFN, and signal transducer and activator of transcription 1 (STAT1)
      phosphorylation, a critical step in the IFN-signaling pathway, along with
      increased numbers of plasmacytoid dendritic cells. These data challenge the
      current paradigm of cGVHD as a type II cytokine-driven disorder and support the
      model that oral cGVHD results from type I IFN-driven immigration, proliferation,
      and differentiation of T-bet(+) type I T effectors. The clinical trials are
      registered at http://www.clinicaltrials.gov as NCT00331968.

PMID- 19168794
TI  - High GATA-2 expression inhibits human hematopoietic stem and progenitor cell
      function by effects on cell cycle.
AB  - Evidence suggests the transcription factor GATA-2 is a critical regulator of
      murine hematopoietic stem cells. Here, we explore the relation between GATA-2 and
      cell proliferation and show that inducing GATA-2 increases quiescence (G(0)
      residency) of murine and human hematopoietic cells. In human cord blood,
      quiescent fractions (CD34(+)CD38(-)Hoechst(lo)Pyronin Y(lo)) express more GATA-2
      than cycling counterparts. Enforcing GATA-2 expression increased quiescence of
      cord blood cells, reducing proliferation and performance in long-term culture
      initiating cell and colony-forming cell (CFC) assays. Gene expression analysis
      places GATA-2 upstream of the quiescence regulator MEF, but enforcing MEF
      expression does not prevent GATA-2-conferred quiescence, suggesting additional
      regulators are involved. Although known quiescence regulators p21(CIP1) and
      p27(KIP1) do not appear to be responsible, enforcing GATA-2 reduced expression of
      regulators of cell cycle such as CCND3, CDK4, and CDK6. Enforcing GATA-2
      inhibited human hematopoiesis in vivo: cells with highest exogenous expression
      (GATA-2(hi)) failed to contribute to hematopoiesis in nonobese diabetic-severe
      combined immunodeficient (NOD-SCID) mice, whereas GATA-2(lo) cells contributed
      with delayed kinetics and low efficiency, with reduced expression of Ki-67. Thus,
      GATA-2 activity inhibits cell cycle in vitro and in vivo, highlighting GATA-2 as
      a molecular entry point into the transcriptional program regulating quiescence in
      human hematopoietic stem and progenitor cells.

PMID- 19168795
TI  - PKCbeta is essential for the development of chronic lymphocytic leukemia in the
      TCL1 transgenic mouse model: validation of PKCbeta as a therapeutic target in
      chronic lymphocytic leukemia.
AB  - The development and the propagation of chronic lymphocytic leukemia (CLL) has
      been linked to signaling via the B-cell receptor (BCR). Protein kinase C beta
      (PKCbeta) is an essential signaling element of the BCR and was recently shown to
      be overexpressed in human CLL. We used the TCL1 transgenic mouse model to
      directly target PKCbeta in the development of murine CLL. TCL1 overexpression did
      restore the CD5(+) B-cell population that is absent in PKCbeta-deficient mice.
      However, PKCbeta-deleted TCL1 transgenic mice did not develop a CLL disease,
      suggesting a role of PKCbeta in the establishment of the malignant clone.
      Moreover, targeting of PKCbeta with the specific inhibitor enzastaurin led to
      killing of human CLL samples in vitro. We thus propose that PKCbeta may be a
      relevant target for the treatment of CLL.

PMID- 19168796
TI  - Proteomics and pathway analysis identifies JNK signaling as critical for high
      linear energy transfer radiation-induced apoptosis in non-small lung cancer
      cells.
AB  - During the past decade, we have witnessed an explosive increase in generation of
      large proteomics data sets, not least in cancer research. There is a growing need
      to extract and correctly interpret information from such data sets to generate
      biologically relevant hypotheses. A pathway search engine (PSE) has recently been
      developed as a novel tool intended to meet these requirements. Ionizing radiation
      (IR) is an anticancer treatment modality that triggers multiple signal
      transduction networks. In this work, we show that high linear energy transfer
      (LET) IR induces apoptosis in a non-small cell lung cancer cell line, U-1810,
      whereas low LET IR does not. PSE was applied to study changes in pathway status
      between high and low LET IR to find pathway candidates of importance for high LET
      induced apoptosis. Such pathways are potential clinical targets, and they were
      further validated in vitro. We used an unsupervised shotgun proteomics approach
      where high resolution mass spectrometry coupled to nanoflow liquid chromatography
      determined the identity and relative abundance of expressed proteins. Based on
      the proteomics data, PSE suggested the JNK pathway (p = 6.10(-6)) as a key event
      in response to high LET IR. In addition, the Fas pathway was found to be
      activated (p = 3.10(-5)) and the p38 pathway was found to be deactivated (p =
      0.001) compared with untreated cells. Antibody-based analyses confirmed that high
      LET IR caused an increase in phosphorylation of JNK. Moreover pharmacological
      inhibition of JNK blocked high LET-induced apoptotic signaling. In contrast,
      neither an activation of p38 nor a role for p38 in high LET IR-induced apoptotic
      signaling was found. We conclude that, in contrast to conventional low LET IR,
      high LET IR can trigger activation of the JNK pathway, which in turn is critical
      for induction of apoptosis in these cells. Thus PSE predictions were largely
      confirmed, and PSE was proven to be a useful hypothesis-generating tool.

PMID- 19168797
TI  - Motivations of hospice volunteers.
AB  - To recruit and retain volunteers, coordinators need to understand volunteers'
      motivations. In this study, 351 volunteers from 32 hospices in the western United
      States answered questions on a mailed survey about their motivations. The
      motivations reported were, in order of overall importance: to help others and
      learn, foster social relationships, feel better, and pursue career goals. Younger
      volunteers reported stronger career motivations, and retired and unemployed
      volunteers reported stronger social motivations. Volunteer coordinators should
      consider these motivations in communicating with potential and current
      volunteers, with special emphasis on compassion for those in need and the
      importance of helping, on fostering hospice volunteering as a learning
      experience, and in accessing and building social networks around hospice
      volunteering.

PMID- 19168802
TI  - Influence of controlled rheumatoid arthritis on the action and disposition of
      verapamil: focus on infliximab.
AB  - Active rheumatoid arthritis (RA), obesity, and old age are associated with
      reduced responsiveness to the calcium channel antagonist verapamil despite
      increased drug concentrations. The diminishing effect appears to be associated
      with the severity of inflammation. We examined pharmacodynamics and
      pharmacokinetics of verapamil in patients with controlled RA. Volunteers included
      RA patients in remission: 12 on infliximab, 8 on other antirheumatic therapy, and
      12 healthy subjects. Verapamil plasma concentrations and selected inflammatory
      mediators as well as blood pressure and electrocardiographic parameters were
      recorded after a single 80-mg dose of verapamil. Inflammatory mediators were all
      below what is reported for active RA, confirming that RA was controlled. The
      tumor necrosis factor-alpha concentration, however, was significantly higher in
      the infliximab group compared with other groups and the literature value for
      active RA. No significant difference was observed between groups in terms of
      percentage prolongation of PR interval despite a trend toward a lower response in
      the RA groups, the mean plasma concentrations, and the total and unbound area
      under the curve of verapamil. However, the slope of the S-verapamil concentration
      effect curve was steeper for controls compared with the RA patients. Remission
      from active disease appears to restore plasma protein levels and hepatic drug
      metabolism activity in patients with RA, resulting in relatively normal verapamil
      pharmacokinetics.

PMID- 19168803
TI  - Repair of distal biceps tendon rupture using a suture anchor: description of a
      new endoscopic procedure.
AB  - BACKGROUND: Repair of a distal biceps tendon rupture is a challenging procedure
      and, to date, there is no consensus as to which technique should be used because
      of the specific complications reported for each. PURPOSE: A new endoscopic
      technique is described that uses a suture anchor to repair distal biceps tendon
      ruptures. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The results
      of a cohort of 23 patients (25 elbows) are reported with a median follow-up of 26
      months. All patients were male and their median age was 44 years (range, 30-58).
      Ten of the patients (12 ruptures) were professional athletes or had a high level
      of physical activity. All repairs were performed via a 3-cm incision made in the
      "safe area" of the anterior crease of the forearm. The whole procedure was
      performed within the tendon sheath. The tendon was reinserted using a single
      anchor. RESULTS: Of the 23 patients, 22 were satisfied and 20 patients returned
      to their preinjury sports and jobs. There was a mean loss of 8.6 degrees of
      pronation and 5 degrees of supination. A single severe neurologic complication,
      which required a second surgical procedure, was reported. There were also 2
      ectopic ossifications without clinical consequences and a transitory radial nerve
      paralysis. CONCLUSIONS: This study clearly demonstrated that endoscopic repair of
      the ruptured distal biceps tendon is safe, effective, and reproducible. It
      provides good functional outcome and early recovery with few complications.
      Postoperative median nerve palsy due to edema is a possible concern for patients
      involved in athletic activity and with a history of nerve entrapment; thus this
      technique should be used with caution in this group of patients.

PMID- 19168804
TI  - Hyaluronic acid viscosupplementation and osteoarthritis: current uses and future
      directions.
AB  - Intra-articular hyaluronic acid viscosupplementation is gaining popularity as a
      treatment option in the nonoperative management of patients with osteoarthritis.
      Recent clinical studies have demonstrated that the anti-inflammatory, anabolic,
      and chondroprotective actions of hyaluronic acid reduce pain and improve patient
      function. With evidence mounting in support of the efficacy of this treatment
      modality for patients with osteoarthritis, its potential use in additional
      patient populations and for other pathologies affecting the knee is being
      investigated. The current article reviews the use of intra-articular hyaluronic
      acid viscosupplementation in the management of knee osteoarthritis and presents
      the potential for expanding its indications for other joints and alternative
      patient subpopulations. Additionally, future directions for the use of hyaluronic
      acid and areas of active research are discussed.

PMID- 19168805
TI  - Primary repair combined with bone marrow stimulation in acute anterior cruciate
      ligament lesions: results in a group of athletes.
AB  - BACKGROUND: The anterior cruciate ligament has been shown to have poor healing
      ability, and reconstruction is the standard treatment. HYPOTHESIS: Primary
      anterior cruciate ligament repair combined with bone marrow stimulation could
      restore stability and function in athletes with acute anterior cruciate ligament
      incomplete tears. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Among
      a group of 99 patients with clinically diagnosed anterior cruciate ligament acute
      lesions, 26 athletes with arthroscopically confirmed incomplete anterior cruciate
      ligament proximal tears were treated with primary repair combined with bone
      marrow stimulation of the anterior cruciate ligament femoral attachment site.
      Postoperatively, all patients underwent a specific rehabilitation program. All
      patients were prospectively evaluated; outcome measures were assessed using Marx,
      Noyes, Tegner, Single Assessment Numeric Evaluation, Lysholm, and International
      Knee Documentation Committee scores. Anterior tibial translation was measured
      using Rolimeter instrument under anesthesia and at final follow-up. RESULTS: All
      athletes were followed up for a mean 25.3 months (range, 17-38 months). Mean age
      was 26.6 years. Mean preinjury Tegner was 7.1 (SD, 1.1) and final Tegner 6.7 (SD,
      1.4); mean preinjury Marx was 11.0 (SD, 3.4) and final Marx 9.6 (SD, 3.1); mean
      preinjury Noyes was 82.5 (SD, 5.8) and final Noyes 83.3 (SD, 7.2). These scores
      were not statistically different at P values of .020, .011, and .303,
      respectively. Final Single Assessment Numeric Evaluation rating was significantly
      lower than was preinjury Single Assessment Numeric Evaluation rating. This was
      mainly related to decreased self-confidence in high-risk sports and fear of new
      injury. Final Single Assessment Numeric Evaluation rating and Tegner scores were
      significantly higher than were their respective preoperative values. Mean
      Rolimeter side-to-side difference of anterior knee translation was significantly
      reduced from 3.5 mm (SD, 0.7) preoperatively to 1.3 mm (SD, 0.8) postoperatively.
      CONCLUSION: In this athletic population, anterior cruciate ligament primary
      repair in acute incomplete lesion combined with bone marrow stimulation
      effectively restored knee stability and function.

PMID- 19168806
TI  - Biomechanical evaluation of bioabsorbable versus metallic screws for posterior
      cruciate ligament inlay graft fixation: a comparative study.
AB  - BACKGROUND: Although a tibial inlay technique for posterior cruciate ligament
      reconstruction is advantageous, metallic screw fixation of the bone block is
      required. This may pose problems for future surgery (eg, osteotomies, total knee
      replacement). HYPOTHESIS: There is no significant difference in the biomechanical
      integrity of bone block fixation using stainless steel versus bioabsorbable screw
      fixation of the tibial inlay graft in posterior cruciate ligament reconstruction.
      STUDY DESIGN: Controlled laboratory study. METHODS: Fourteen human cadaveric
      knees were randomized to receive either stainless steel or bioabsorbable screw
      fixation of a bone-patellar tendon-bone graft. Cyclic tensile testing of each
      construct was performed, followed by a load-to-failure test. Digital video
      digitization was used to optically determine tendon graft deformation. RESULTS:
      Cyclic creep deformation showed no significant difference between the 2 groups (P
      = .8). The failure load (stainless steel, 461 +/- 231 N; bioabsorbable, 638 +/-
      492 N; P = .7) and linear stiffness (stainless steel, 116 +/- 22 N/mm,
      bioabsorbable, 106 +/- 44 N/mm; P = .6) also showed no significant difference
      between the 2 groups. Optically measured graft deformation was not significant
      for distal (P = .7) and midsubstance (P = .8) regions, while proximal deformation
      was significantly higher for bioabsorbable fixation (P = .02). All samples failed
      at the tibial insertion site with the tibial bone block fracturing at the screws.
      CONCLUSION: Bioabsorbable screw fixation using a tibial inlay technique does not
      compromise the strength and stiffness characteristics afforded by metallic
      fixation. From a biomechanical perspective, bioabsorbable screws are a viable
      alternative to metal in the context of tibial inlay reconstruction. CLINICAL
      RELEVANCE: Use of bioabsorbable fixation can potentially eliminate future
      hardware problems after posterior cruciate ligament reconstruction using a tibial
      inlay technique.

PMID- 19168807
TI  - Comparison of single- versus double-tunnel tendon-to-bone healing in an ovine
      model: a biomechanical and histological analysis.
AB  - BACKGROUND: The double-bundle technique has recently gained much interest in
      ligament reconstruction. In addition to potential kinematic advantages, perhaps
      double tunnels have the potential for faster and more secure tendon-to-bone
      healing. HYPOTHESIS: Placement of tendons in 2 osseous tunnels, as opposed to 1,
      will enhance tendon fixation as determined biomechanically and histologically.
      STUDY DESIGN: Controlled laboratory study. METHODS: Fourteen sheep were used, and
      an extra-articular tendon graft reconstruction was performed on both knees of
      each sheep. In 1 randomly selected knee, the long digital extensor tendon was
      released from the femur and placed into a single tunnel in the proximal tibia. In
      the contralateral knee, the tendon was split and placed into 2 tibial tunnels.
      Ten sheep were analyzed by mechanical testing, and the remaining 4 were subjected
      to histologic evaluation at 6 weeks after surgery. Paired t tests were used for
      statistical analysis. RESULTS: Mechanical testing demonstrated that the peak load
      (981.8 +/- 143.2 N, mean +/- SD) and stiffness (570.9 +/- 114.6 N/mm) at 6 weeks
      after surgery in the double-tunnel group were significantly greater than for the
      single-tunnel group (714.8 +/- 94.2 N and 432.2 +/- 56.7 N/mm, respectively;
      load, P = .007; stiffness, P = .03). Histologic analysis suggested similar tendon
      to-bone healing for both groups. CONCLUSION: This study demonstrated enhanced
      biomechanical fixation of the tendon to the surrounding bone in the double-tunnel
      compared with the single-tunnel technique in this ovine model. CLINICAL
      RELEVANCE: The double-tunnel technique may provide better fixation and healing in
      human ligament reconstruction.

PMID- 19168808
TI  - Football playing surface and shoe design affect rotational traction.
AB  - BACKGROUND: High rotational traction between football shoes and the playing
      surface may be a potential mechanism of injury for The abstract goes here and
      covers two columns. the lower extremity. HYPOTHESIS: Rotational traction at the
      shoe-surface interface depends on shoe design and surface type. STUDY DESIGN:
      Controlled laboratory study. METHODS: A mobile testing apparatus with a compliant
      ankle was used to apply rotations and measure the torque at the shoe-surface
      interface. The mechanical surrogate was used to compare 5 football cleat patterns
      (total of 10 shoe models) and 4 football surfaces (FieldTurf, AstroPlay, and 2
      natural grass systems) on site at actual surface installations. RESULTS: Both
      artificial surfaces yielded significantly higher peak torque and rotational
      stiffness than the natural grass surfaces. The only cleat pattern that produced a
      peak torque significantly different than all others was the turf-style cleat, and
      it yielded the lowest torque. The model of shoe had a significant effect on
      rotational stiffness. CONCLUSION: The infill artificial surfaces in this study
      exhibited greater rotational traction characteristics than natural grass. The
      cleat pattern did not predetermine a shoe's peak torque or rotational stiffness.
      A potential shoe design factor that may influence rotational stiffness is the
      material(s) used to construct the shoe's upper. CLINICAL RELEVANCE: The study
      provides data on the rotational traction of shoe-surface interfaces currently
      employed in football. As football shoe and surface designs continue to be
      updated, new evaluations of their performance must be assessed under simulated
      loading conditions to ensure that player performance needs are met while
      minimizing injury risk.

PMID- 19168809
TI  - Biomechanical comparison of the docking technique with and without humeral
      bioabsorbable interference screw fixation.
AB  - BACKGROUND: Surgical reconstruction of the ulnar collateral ligament has evolved
      since Frank Jobe's original description. The "docking technique" is a popular
      modification that allows for securing the graft within a single humeral tunnel.
      More recently, interference screw fixation has been introduced as a means of
      improving the ultimate strength, stiffness, and kinematics of these constructs.
      PURPOSE: This study was conducted to compare the biomechanical performance of the
      docking technique with and without interference screw fixation in the humerus.
      STUDY DESIGN: Controlled laboratory study. METHODS: Nine matched pairs of human
      cadaveric elbows (age 49.9 +/- 8.0 years) were reconstructed with a tendon graft
      using the docking technique (group 1) or the docking technique with the addition
      of a 4.75-mm bioabsorbable humeral interference screw (group 2). Before the
      reconstruction, joint laxity was measured on each specimen with the ulnar
      collateral ligament intact and then after transection of the ligament. Laxity
      measurements were repeated after the reconstruction. Failure testing was then
      performed at 70 degrees of elbow flexion. The specimens were preloaded with a 1
      N.m moment and then loaded to failure at a displacement rate of 14 mm/s to
      approximate 50% strain per second. RESULTS: Within group 1, the elbow laxity of
      the reconstructed state was significantly greater than the intact state at all
      tested flexion angles (P < .021). Within group 2, no statistically significant
      difference existed in elbow laxity between the intact state and the reconstructed
      state. When comparing laxities between groups, group 1 tended to be more lax at
      all tested flexion angles but was only significantly greater at 105 degrees of
      flexion. The most common mode of failure for both groups involved the sutures
      pulling out of the tendon. No significant difference was found for ultimate
      moment of failure between the 2 groups. However, the moment associated with 3 mm
      of gap formation for group 2 (12.8 +/- 4.2 N x m) was statistically greater than
      that of group 1 (7.5 +/- 1.2 N x m) (P = .001). The stiffness of group 2 (14.7 +/
      6.4 N/mm) was significantly greater than group 1 (9.9 +/- 3.1 N/mm) (P = .044).
      CONCLUSION: The biomechanical performance of the docking technique with and
      without a humeral interference screw is similar. CLINICAL RELEVANCE: The
      stiffness of the construct, along with the difference in moment that allows a 3
      mm gap formation, suggests that the addition of a humeral interference screw is
      potentially beneficial. Further research in a healing model will help clarify
      this benefit.

PMID- 19168810
TI  - Chronic posttraumatic bursitis of the medial collateral ligament: surgical
      treatment in 2 high-level professional athletes.

PMID- 19168812
TI  - Botulinum toxin A injections for the treatment of Schwartz-Jampel syndrome: a
      case series.
AB  - Schwartz-Jampel syndrome is a rare autosomal recessive disorder characterized by
      myotonia and skeletal dysplasia. Botulinum toxin A is emerging as a therapeutic
      option for patients with this syndrome. This study describes the use of botulinum
      toxin A in 4 children with Schwartz-Jampel syndrome. The response to this
      therapeutic modality was limited and variable.

PMID- 19168813
TI  - CDG type Ia and congenital cytomegalovirus infection: two coexisting conditions.
AB  - Congenital disorders of glycosylation are a heterogeneous group of disorders with
      multisystemic involvement. The most common form is phosphomannomutase deficiency
      or congenital disorders of glycosylation type Ia with an autosomal recessive
      inheritance and incidence estimated at 1/20000-1/50000 live born. Congenital
      disorders of glycosylation Ia can manifest as severe multisystemic disease of
      infancy or milder disorder with only neurological problems including ataxia,
      hypotonia, and psychomotor retardation. The brain pathological findings in
      congenital disorders of glycosylation type Ia patients corroborate with
      cerebellar dysfunction. Usually the most affected part is the anterior lobe of
      the vermis. Microscopic analysis demonstrates the prominent Purkinje cell loss
      and subtotal loss of the external and internal granule cell layers. The authors
      present clinical and pathological picture of a 4-month-old girl with congenital
      disorders of glycosylation type Ia, additionally complicated by congenital
      cytomegalovirus infection. The diagnosis was confirmed by low phosphomannomutase
      activity in patient's fibroblasts and mutations on both alleles of
      phosphomannomutase 2 gene.

PMID- 19168815
TI  - Role of TNF-alpha gene variation in idiopathic childhood ischemic stroke: a case
      control study.
AB  - Etiology of the idiopathic childhood stroke remains unknown. In previous studies,
      the immunologic process may be involved in the idiopathic stroke. Tumor necrosis
      factor- alpha (TNF-alpha), an important immune mediator, may contribute to the
      initiation and progression in the stroke. The main purpose of this study was to
      investigate correlation of TNF-alpha genetic variation and idiopathic childhood
      ischemic stroke. Using the direct DNA sequencing method, polymorphisms in the TNF
      alpha promoter region were genotyped in 67 Chinese patients with idiopathic
      childhood stroke and 70 controls. Among totally 7 single nucleotide polymorphisms
      identified in the TNF-alpha promoter region, the variant of the -863C/A is
      associated with increased risk of idiopathic childhood ischemic stroke in our
      study group. TNF-alpha molecule may have genetically as well as functionally an
      important role in the pathogenesis of idiopathic childhood ischemic stroke in the
      Chinese population.

PMID- 19168814
TI  - A sleep habits questionnaire for children with autism spectrum disorders.
AB  - Sleep difficulties in children with autism spectrum disorders are common, with
      poor sleep hygiene a contributing factor. We developed the Family Inventory of
      Sleep Habits to measure sleep hygiene in this population. Its validity and
      reliability in 2 groups of children aged 4 to 10 years, those with a clinical
      diagnosis of autism spectrum disorders, and those who are typically developing
      are described. In both groups, total and modified (reflecting insomnia subscales)
      scores on the Children's Sleep Habits Questionnaire showed significant negative
      correlations with the total score. The Peabody Picture Vocabulary Test-III was
      significantly correlated with total score in the autism spectrum group but not in
      the typically developing group. Age and socioeconomic status were not correlated
      with total score in either group. This preliminary work suggests that the Family
      Inventory of Sleep Habits is a valid and reliable measure of sleep hygiene in
      autism spectrum disorders.

PMID- 19168816
TI  - Blood flow velocities are reduced in the optic nerve of children with elevated
      intracranial pressure.
AB  - The authors previously used spectral Doppler imaging to determine optic nerve
      blood flow velocities in normal children. In the current study, we measured
      central retinal artery and central retinal vein blood flow velocities by spectral
      Doppler imaging in 38 healthy children and 18 children with elevated intracranial
      pressure between ages 4 and 17. We found central retinal artery systolic blood
      flow velocity was significantly reduced in children with elevated increased
      intracranial pressure; ANOVA P = .01 (normal children 8.9 cm/s [SD 1.1] versus
      children with elevated intracranial pressure 7.5 cm/s [SD 1.3]). Central retinal
      vein maximal blood flow velocity was also significantly reduced in children with
      elevated intracranial pressure; ANOVA P < .02 (normal children 4.2 cm/s [SD 0.9]
      versus children with elevated intracranial pressure 3.6 cm/s [SD 0.7]). Spectral
      Doppler imaging is a noninvasive test well tolerated in children that identifies
      blood flow velocity changes in elevated intracranial pressure.

PMID- 19168817
TI  - From fossil to fetus: nonhemorrhagic germinal matrix echodensity caused by
      mineralizing vasculitis--hypothesis of fossilizing germinolysis and gliosis.
AB  - Subventricular echodensities medioventral to the caudate nucleus near the
      caudothalamic groove are regular ultrasonographic findings in preterm infants
      with germinal matrix hemorrhages. The transformation into pseudocysts is termed
      germinolysis. Interestingly, identical ultrasonographic findings are rarely even
      reported for near-term infants. We examined 5 cases of near-term infants
      presenting with various localized subventricular echodensities after various
      noncerebral infections (intra-amniotic infection, gastroenteritis of unidentified
      pathogens, septic wound, and a twin pair with rotavirus gastroenteritis),
      suggesting an inflammatory or ischemic rather than a hemorrhagic etiology. With
      high-resolution ultrasonography, these lesions showed similar characteristics:
      all were space-occupying, homogeneous, echodense, and ultimately transformed into
      pseudocysts. Additionally, Doppler ultrasonography showed linear perivascular
      echodensities in the basal ganglia of one infant. All infants were also examined
      by cerebral magnetic resonance imaging (MRI) including T2*-weighted gradient-echo
      sequences so that subventricular hemorrhages could be excluded in 4 infants. One
      of these 4 infants died unexpectedly at home. Brain autopsy revealed
      nonhemorrhagic germinal matrix pseudocysts with gliotic walls. Based on our
      findings and the original literature, we favored an ischemic infarction of the
      strongly vascularized and highly metabolic germinal matrix as cause of this
      germinolysis and gliosis. We postulated that the infarction was the result of an
      obstructive and possibly mineralizing, or even fossilizing vasculopathy due to an
      inflammatory response. The precise pathogenesis of the suspected immune-mediated
      vasculitis remains unknown. We concluded that cerebral ultrasonography should be
      performed in infants with noncerebral infection and that it should be
      complemented by MRI in cases of subventricular echodensities to prove or to
      exclude a germinal matrix hemorrhage.

PMID- 19168818
TI  - Mutations in the MECP2 gene are not a major cause of Rett syndrome-like or
      related neurodevelopmental phenotype in male patients.
AB  - Rett syndrome is a genetic neurodevelopmental disorder that affects mainly girls,
      but mutations in the causative MECP2 gene have also been identified in boys with
      classic Rett syndrome and Rett syndrome-like phenotypes. We have studied a group
      of 28 boys with a neurodevelopmental disorder, 13 of which with a Rett syndrome
      like phenotype; the patients had diverse clinical presentations that included
      perturbations of the autistic spectrum, microcephaly, mental retardation, manual
      stereotypies, and epilepsy. We analyzed the complete coding region of the MECP2
      gene, including the detection of large rearrangements, and we did not detect any
      pathogenic mutations in the MECP2 gene in these patients, in whom the genetic
      basis of disease remained unidentified. Thus, additional genes should be screened
      in this group of patients.

PMID- 19168819
TI  - Cranial ultrasound lesions in the NICU predict cerebral palsy at age 2 years in
      children born at extremely low gestational age.
AB  - Our prospective cohort study of extremely low gestational age newborns evaluated
      the association of neonatal head ultrasound abnormalities with cerebral palsy at
      age 2 years. Cranial ultrasounds in 1053 infants were read with respect to
      intraventricular hemorrhage, ventriculomegaly, and echolucency, by multiple
      sonologists. Standardized neurological examinations classified cerebral palsy,
      and functional impairment was assessed. Forty-four percent with ventriculomegaly
      and 52% with echolucency developed cerebral palsy. Compared with no ultrasound
      abnormalities, children with echolucency were 24 times more likely to have
      quadriparesis and 29 times more likely to have hemiparesis. Children with
      ventriculomegaly were 17 times more likely to have quadriparesis or hemiparesis.
      Forty-three percent of children with cerebral palsy had normal head ultrasound.
      Focal white matter damage (echolucency) and diffuse damage (late
      ventriculomegaly) are associated with a high probability of cerebral palsy,
      especially quadriparesis. Nearly half the cerebral palsy identified at 2 years is
      not preceded by a neonatal brain ultrasound abnormality.

PMID- 19168820
TI  - Serum and muscle carnitine levels in epileptic children receiving sodium
      valproate.
AB  - The purpose of this study was to determine whether children with epilepsy
      undergoing valproate therapy and who are otherwise healthy have lower levels of
      serum and muscle carnitine. A total of 50 patients with epilepsy, 3 to 14 years
      of age, who were treated solely with valproate and free of abnormal neurologic
      findings or nutritional problems were selected. The control group consisted of 30
      healthy children. The total carnitine levels in serum were 28.1 +/- 10.3 and 55.6
      +/-7.3 microg/mL, and the free carnitine levels in serum were 16.5 +/-10.2 and
      44.6 +/-7.3 microg/mL, the total carnitine levels in muscle were 12.1 +/- 1.8 and
      45.3 +/- 5.9 micromol/g noncollagen protein and the free carnitine levels in
      muscle were 5.6 +/- 1.6 and 39.3 +/- 6.0 micromol/g noncollagen protein in the
      valproic acid-treated and control groups, respectively (P < .05). In conclusion,
      valproate monotherapy depletes both muscle and serum carnitine levels in
      otherwise healthy epileptic children.

PMID- 19168821
TI  - Megalencephalic leukoencephalopathy with subcortical cysts in a Tunisian boy.
AB  - Megalencephalic leukoencephalopathy with subcortical cysts is an autosomal
      recessive cerebral white-matter disorder in children. Megalencephalic
      leukoencephalopathy with subcortical cysts is caused by mutation in the
      megalencephalic leukoencephalopathy with subcortical cysts gene 1. The authors
      report a case of a 2-year-old Tunisian boy who had presented seizure following
      minor head trauma. He had megalencephaly, cerebellar ataxia, and mild pyramidal
      signs at physical examination. Magnetic resonance imaging showed extensive white
      matter signal changes involving the corpus callosum and temporal subcortical
      cysts consistent with megalencephalic leukoencephalopathy with subcortical cysts.
      The molecular genetic study of the megalencephalic leukoencephalopathy with
      subcortical cysts gene 1 identified a homozygous mutation C46fsX57 in the
      patient. The mutation was found to be heterozygous in the parents. To the best of
      the authors' knowledge, this mutation has never been reported.

PMID- 19168822
TI  - Magnetic resonance imaging, magnetic resonance spectroscopy, and facial
      dysmorphism in a case of Lowe syndrome with novel OCRL1 gene mutation.
AB  - Lowe syndrome is a multisystem disorder characterized by anomalies of the eye,
      the nervous system, and the kidney. It is an uncommon, X-linked disease.
      Bilateral cataract and severe hypotonia are present at birth. Psychomotor
      retardation is evident in childhood, while renal complications arise in
      adolescence. The mutation of the gene OCRL1 localized at Xq26.1 is responsible
      for the disease. The authors report on a 12-year-old male with mental
      retardation, facial dysmorphism as prominent forehead, long and slender-shaped
      face, prominent eyebrows, epicanthus, microphthalmia, low-posterior set ears with
      prominent helix and antihelix, long philtrum, and mild prognathia. He also had
      history of neonatal hypotonia and congenital cataracts. His cranial magnetic
      resonance imaging showed increased signal intensity in white matter on T2
      weighted images, and magnetic resonance spectroscopy revealed elevation of the
      myoinositol peak at 3.56 ppm. Molecular analysis of OCRL1 gene revealed novel
      N574K mutation on 17th exon.

PMID- 19168823
TI  - Prenatal microcephaly: can we be more accurate?
AB  - Consultation regarding isolated fetal microcephaly is especially difficult in a
      genetically heterogeneous population, as one of the factors associated with head
      circumference difference is ethnicity. The study presents four women referred to
      the neuro-fetal clinic for isolated fetal microcephaly. All fetuses had normal
      chromosomes, no structural abnormalities, or evidence of intrauterine infection
      or intoxication. Their head circumference measurements were 2 to 3 standard
      deviations below average for age on repeat ultrasound and fetal magnetic
      resonance imaging. Striking differences in chart placements were found between
      different professionals using different charts. In all children, measured head
      circumference after birth/termination was within normal limits. This study
      suggests that national charts should be built measuring fetal size adjusted for
      ethnicity and based on a genetically heterogeneous population. The charts should
      be customized between different professionals assessing prenatal and postnatal
      head circumference.

PMID- 19168824
TI  - Agenesis of internal carotid artery in a child with ipsilateral Horner's
      syndrome.
AB  - Horner's syndrome is characterized by a classic triad of ipsilateral pupillary
      miosis, partial eyelid ptosis, and facial anhydrosis. This case study reports a 7
      year-old boy with right miosis, mild blepharoptosis, and iris hypopigmentation
      detected in a routine pediatric follow-up without ipsilateral facial anhydrosis,
      flushing, or pain. There was no history of birth trauma and test with cocaine
      provoked no response of the right pupil, suggesting right Horner's syndrome.
      Mediastinal tumor was ruled out and brain magnetic resonance imaging incidentally
      showed absence of flow in the right internal carotid artery. Subsequent magnetic
      resonance angiography demonstrated agenesis of the right internal carotid artery
      without other vascular-associated malformations. The final diagnosis was right,
      congenital Horner's syndrome due to ipsilateral internal carotid agenesis. We
      describe in detail the radiological findings and pathophysiological mechanisms of
      this unusual association.

PMID- 19168825
TI  - Unilateral venous thalamic infarction in a child mimicking a thalamic tumor.
AB  - Unilateral thalamic infarction is a rare condition in adults. This is a case
      report of a young child presenting with left-sided hemiparesis of sudden onset
      due to an unilateral venous thalamic infarction. This was attributed to an
      asymmetric thrombosis of the cerebral internal veins, a partial thrombosis of the
      vein of Galen and straight sinus. Magnetic resonance imaging resulted primarily
      in the differential diagnosis of a cerebral tumor or an intracerebral abscess,
      leading to stereotactic puncture. Subsequent magnetic resonance venography
      facilitated the correct diagnosis. Heparin-induced thrombocytopenia necessitated
      anticoagulation treatment with hirudin and later, warfarin. The patient made a
      complete recovery. We conclude that unclear unilateral thalamic lesions might be
      symptomatic of a cerebral deep venous thrombosis and might mimic a thalamic
      tumor. In uncertain cases, we suggest rapid performance of magnetic resonance
      angiography.

PMID- 19168826
TI  - Cerebral sinus venous thrombosis complicated by cerebellar hemorrhage in a child
      with acute promyelocytic leukemia.
AB  - A 12-year-old boy who presented with headache and papilledema was diagnosed with
      cerebral sinus venous thrombosis and promyelocytic leukemia. Cerebral sinus
      venous thrombosis is an uncommon manifestation of acute promyelocytic leukemia,
      and acute promyelocytic leukemia is an unusual etiology for cerebral sinus venous
      thrombosis. This case highlights the importance of a complete evaluation for risk
      factors in a child presenting with cerebral sinus venous thrombosis.
      Anticoagulation was initiated for treatment of cerebral sinus venous thrombosis,
      and new asymptomatic hemorrhage was identified in the cerebellum 1 day later.
      Anticoagulation was discontinued for 5 days and then reinitiated in the intensive
      care unit without hemorrhage expansion or other complications. We review the
      literature regarding anticoagulation in children with cerebral sinus venous
      thrombosis and issues specific to acute promyelocytic leukemia. This case
      suggests that in a controlled setting, anticoagulation may be safe in selected
      patients with cerebellar hemorrhage.

PMID- 19168827
TI  - From eugenic euthanasia to habilitation of "disabled'' children: Andreas Rett's
      contribution.
AB  - Although the name of Andreas Rett is familiar to many from his eponymous
      neurogenetic syndrome, his other achievements involving the care of disabled
      children deserve special attention. His tireless advocacy helped to bring
      fundamental changes in the medical and societal attitude toward disabled
      individuals in a city that had recently seen more than 7500 disabled children and
      inmates of psychiatric hospitals actively euthanized by National Socialist (Nazi)
      decree. Most notably, this study demonstrates the remarkable changes that can be
      achieved single-handedly by a vocal and energetic physician. Yet at the same
      time, several instances are recorded in which Rett appeared to prioritize his own
      professional advancement at the expense of truthful disclosure of his own past,
      as well as that of some of his close associates. Dr Rett's professional life and
      contributions, now 10 years after his death, presents a compelling object lesson
      for neurologists and others involved in the care of the disabled.

PMID- 19168828
TI  - Schizencephaly in infants with thrombophilia.
AB  - Schizencephaly is an uncommon congenital malformation of neuronal migration
      characterized by a gray matter-lined cleft extending from the pial surface to the
      ependymal surface of the lateral ventricles. Its etiology is heterogeneous and
      consists of hereditary factors or destructive processes that occur during the
      second trimester of pregnancy. We report 2 cases with schizencephaly and
      thrombophilia caused by mutations of the methyltetrahydrofolate reductase and the
      factor V Leiden genes. Their clinical presentations included motor deficits and
      mild cognitive deficits.

PMID- 19168829
TI  - Evaluation of neurological complications in pediatric liver transplant
      recipients: MRI versus CT.
AB  - With the aim of guiding choice of the best imaging modality for specific clinical
      conditions, we retrospectively evaluated neuroradiological findings in pediatric
      liver transplant recipients with neurological complications. Computed tomography
      (CT) was used to examine 31 patients with acute neurological symptoms after liver
      transplantation, and magnetic resonance imaging (MRI) was used for 35 such
      patients. A total of 16 patients belonged to both groups. Headache was the most
      common symptom in patients with computed tomography; seizure was most common
      among patients with magnetic resonance imaging. Magnetic resonance imaging
      detected additional abnormalities in 5 patients presenting with seizures whose
      computed tomography results were normal or insufficient to explain the clinical
      picture. In conclusion, liver transplant recipients with seizure should undergo
      magnetic resonance imaging emergently when possible; omitting computed
      tomography. Choice of imaging modality should be directed by nature of symptoms
      and time interval between transplantation and symptom onset.

PMID- 19168830
TI  - Paramyotonia congenita in 22 members of an Arab (Omani) kindred.
AB  - Paramyotonia congenita in 22 members of Arab (Omani) family is reported. Four
      generations were affected. All had early onset around 1 year of age, with
      myotonia and cold intolerance. Age of onset in the index case was at 3 months of
      age. Six members with the disease were examined and investigated. To our
      knowledge, this is the first report of the condition from this region. Childhood
      presentation and differential diagnosis is discussed.

PMID- 19168831
TI  - Paroxysmal tonic upgaze presenting as a clinical isolated syndrome.
AB  - We report a 3.5-year-old boy with sudden onset of episodic upward deviation of
      the eyes that led to diagnosis of paroxysmal tonic upgaze. Cranial magnetic
      resonance imaging showed right-hand side dominant bilateral hyperintense lesions
      in the mesencephalon and the thalamus on T2-weighted images. These lesions
      suggested a demyelinating pathology. Corticosteroid treatment was started. The
      episodes of upward eye deviation and the lesions on magnetic resonance imaging
      completely resolved after 3 days and 3 months, respectively. After 2 years of
      follow-up, he was symptom-free. Our patient with an isolated brain stem syndrome
      and no mental status changes was diagnosed as having a clinical isolated
      syndrome.

PMID- 19168832
TI  - Clinical characteristics of benign convulsions with rotavirus gastroenteritis.
AB  - Convulsions sometimes occur in infants and toddlers with mild gastroenteritis. We
      retrospectively investigated the hospital records of 106 patients admitted to our
      hospital who had rotavirus gastroenteritis from February 2002 to April 2008.
      There were 23 patients with convulsions, including 13 with benign convulsions, 9
      with febrile seizures, and 1 with epilepsy. Gastroenteritis in patients with
      benign convulsions was mild from the viewpoint of body weights and serum
      creatinine concentrations on admission and the duration of admission. Serum Na(+)
      and Cl(-) concentrations of patients with benign convulsions were relatively
      lower than those without convulsions on admission (P = .006, and P = .008,
      respectively). Twelve of thirteen patients had no other seizures after oral
      administration of 5 mg/kg of carbamazepine, while 1 patient had 1 convulsion 15
      minutes after the therapy. In conclusion, carbamazepine therapy was effective for
      benign convulsions with rotavirus gastroenteritis.

PMID- 19168833
TI  - The soluble terminal complement complex (SC5b-9) up-regulates osteoprotegerin
      expression and release by endothelial cells: implications in rheumatoid
      arthritis.
AB  - OBJECTIVE: Complement activation products contribute to a large number of
      inflammatory diseases, including RA. We have investigated whether osteoprotegerin
      (OPG) may concur with the soluble terminal complement complex (SC5b-9) to the
      inflammatory cascade characterizing RA. METHODS: Levels of SC5b-9 and OPG in the
      plasma and SF of patients with active RA were determined by ELISA. The presence
      of SC5b-9 and OPG in RA synovial lesions was analysed by immunohistochemistry.
      Cultured endothelial cells were used for in vitro leucocyte/endothelial cell
      adhesion assays. In addition, endothelial cells were exposed to SC5b-9 in order
      to evaluate the effects on the production of OPG protein, as well as the
      activation of the OPG promoter. RESULTS: Patients affected by active RA are
      characterized by elevated levels of both SC5b-9 and OPG in plasma and/or SF. Of
      note, we have observed a co-localization of SC5b-9 and OPG in endothelial cells
      of post-capillary venules of RA synovial lesions. Data on endothelial cell
      cultures showed that exposure to SC5b-9 induced the up-regulation of OPG
      expression/release, stimulating the transcriptional activity of the OPG promoter,
      and synergized with TNF-alpha in up-regulating OPG production. CONCLUSIONS: Our
      findings demonstrate that SC5b-9 induces OPG production by endothelial cells and
      we propose that the SC5b-9-mediated up-regulation of OPG may be an important
      mechanism whereby complement contributes in promoting and/or enhancing the
      inflammation in RA.

PMID- 19168834
TI  - Congratulations to the 2008 RSNA Outstanding Educator: Richard B. Gunderman, MD,
      PhD.

PMID- 19168835
TI  - CT diagnosis of chronic pulmonary thromboembolism.
AB  - Chronic pulmonary thromboembolism is mainly a consequence of incomplete
      resolution of pulmonary thromboembolism. Increased vascular resistance due to
      obstruction of the vascular bed leads to pulmonary hypertension. Chronic
      thromboembolic pulmonary hypertension is clearly more common than previously was
      thought, and misdiagnosis is common because patients often present with
      nonspecific symptoms related to pulmonary hypertension. Computed tomography (CT)
      is a useful alternative to conventional angiography not only for diagnosing
      chronic pulmonary thromboembolism but also for determining which cases are
      treatable with surgery and confirming technical success postoperatively. The
      vascular CT signs include direct pulmonary artery signs (complete obstruction,
      partial obstruction, eccentric thrombus, calcified thrombus, bands, webs,
      poststenotic dilatation), signs related to pulmonary hypertension (enlargement of
      main pulmonary arteries, atherosclerotic calcification, tortuous vessels, right
      ventricular enlargement, hypertrophy), and signs of systemic collateral supply
      (enlargement of bronchial and nonbronchial systemic arteries). The parenchymal
      signs include scars, a mosaic perfusion pattern, focal ground-glass opacities,
      and bronchial anomalies. The presence of one or more of these radiologic signs
      arouses suspicion and allows diagnosis of this entity. Early recognition of
      chronic pulmonary thromboembolism may help improve the outcome, since the
      condition is potentially curable with pulmonary thromboendarterectomy.

PMID- 19168836
TI  - Tumors in the tracheobronchial tree: CT and FDG PET features.
AB  - A variety of tumors, including primary malignant tumors, secondary malignant
      tumors, and benign tumors, can occur in the tracheobronchial tree. Primary
      malignant tumors commonly originate from the surface epithelium or the salivary
      glands, whereas most benign tumors arise from the mesenchymal tissue. At computed
      tomography (CT), primary malignant tumors manifest as a polypoid lesion, a focal
      sessile lesion, eccentric narrowing of the airway lumen, or circumferential wall
      thickening. At fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography
      (PET), most squamous cell carcinomas show high uptake, whereas adenoid cystic
      carcinoma and mucoepidermoid carcinoma show variable uptake depending on the
      grade of differentiation. High-grade malignancies tend to show high and
      homogeneous uptake. Carcinoid tumors commonly show intense enhancement at
      contrast material-enhanced CT, which can be helpful in making the diagnosis, and
      usually have lower uptake at FDG PET than would be expected for a malignant
      tumor. Secondary malignant tumors occur as a result of either hematogenous
      metastasis or direct invasion by a malignancy from an adjacent structure. Their
      CT manifestations are similar to those of primary malignant tumors, with uptake
      at FDG PET depending primarily on the metabolic activity and degree of
      differentiation of the primary tumor. Among the benign tumors, hamartoma and
      lipoma can show characteristic CT findings such as "popcorn" calcification or
      internal fat. However, CT findings in most benign tumors are nonspecific. At FDG
      PET, benign tumors usually show little or no uptake and can be differentiated
      from malignant tumors. Knowledge of the characteristic CT and FDG PET findings of
      tracheobronchial tumors can aid in diagnosis and treatment planning.

PMID- 19168837
TI  - Nonspecific interstitial pneumonia: radiologic, clinical, and pathologic
      considerations.
AB  - Nonspecific interstitial pneumonia (NSIP) has variable clinical, pathologic, and
      radiologic manifestations. Cellular and fibrotic NSIP are the two main histologic
      subtypes and differ from one another in the degree of inflammation and fibrosis.
      It is important to differentiate NSIP from other diffuse lung diseases,
      especially usual interstitial pneumonia and hypersensitivity pneumonitis, owing
      to differences in prognosis and treatment. At high-resolution computed
      tomography, the most common findings suggestive of NSIP are lower lobe
      peripherally predominant ground-glass opacity with reticular abnormality,
      traction bronchiectasis, and lower lobe volume loss. Nodules, cysts, and areas of
      low attenuation are uncommon and should point one toward other diagnoses. Because
      many cases of NSIP are associated with collagen vascular diseases, it is
      important to look for associated findings that may suggest an underlying collagen
      vascular disease. Given the difficulty clinicians, pathologists, and radiologists
      experience in making the diagnosis of NSIP, a group approach in which these
      specialists work together to reach a consensus diagnosis has the highest
      likelihood of achieving the correct diagnosis.

PMID- 19168838
TI  - A pattern-based approach to assessment of delayed enhancement in nonischemic
      cardiomyopathy at MR imaging.
AB  - Although delayed contrast material-enhanced cardiac magnetic resonance (MR)
      imaging has traditionally been used to evaluate ischemic disease and myocardial
      viability, it is increasingly being used in the evaluation of nonischemic
      cardiomyopathies. Unlike myocardial infarction, which demonstrates subendocardial
      or transmural delayed contrast enhancement in a vascular distribution,
      nonischemic cardiomyopathies demonstrate enhancement that is not limited to a
      vascular territory. In combination with other cardiac MR imaging features, the
      location (subendocardial, transmural, subepicardial, or mesocardial) and pattern
      (patchy or diffuse) of abnormal delayed myocardial enhancement allow
      differentiation between ischemic (infarct-related) and nonischemic
      cardiomyopathies and, in cases of nonischemic cardiomyopathy, narrowing of the
      differential diagnosis. With use of a structured approach, delayed contrast
      enhanced cardiac MR imaging can be helpful in the early detection and appropriate
      treatment of nonischemic cardiomyopathies.

PMID- 19168839
TI  - Normal and abnormal imaging findings in lumbar total disk replacement: devices
      and complications.
AB  - Fusion, with or without laminectomy, is the standard treatment for symptomatic
      lumbar degenerative disk disease when conservative management has failed. Yet
      even radiographically verified solid fusion may be accompanied by considerable
      long-term problems, including recurrent low back pain, spinal stenosis,
      hypertrophic facet disease, pseudarthrosis, and spondylolysis and
      spondylolisthesis at adjacent levels. Several studies have shown a relationship
      between solid fusion and the development of adjacent-level disk disease, which is
      thought to result from increased stress on, or hypermobility of, adjacent
      segments. Total disk replacement (TDR) was developed as a way to restore normal
      mobility of the diseased segments and improve clinical outcomes by decreasing the
      risk of adjacent-level degenerative disease and related complications. However,
      like fusion, TDR is associated with various complications; some of these (eg,
      migration, subsidence) may occur regardless of the device used, whereas others
      (eg, extrusion of the polyethylene inlay, vertical fractures) are device
      specific. Facet arthrosis, device wear, particle disease, adjacent-level
      degeneration, and heterotopic ossification also have been observed after TDR, but
      the frequency and importance of these findings remain uncertain. Given the
      increasing use of lumbar TDR to treat degenerative disk disease, it is important
      that radiologists be familiar with the most commonly used devices and the
      potential complications of their use.

PMID- 19168840
TI  - Benign and malignant soft-tissue tumors: posttreatment MR imaging.
AB  - Soft-tissue sarcoma requires aggressive treatment, often with a combination of
      radiation therapy, chemotherapy, and surgical resection. Even after multimodality
      treatment, local recurrence is common, and regular follow-up imaging at short
      intervals is required. Interpretation of posttreatment magnetic resonance (MR)
      images may be complicated by changes in the surgical bed or treatment field. The
      challenge of distinguishing posttreatment change from recurrent tumor may be
      minimized by using an organized, systematic approach to imaging, with emphasis on
      the patient's clinical and surgical history and a review of pretreatment images.
      Common changes that result from radiation therapy include soft-tissue
      trabeculation, increased fatty marrow, and focal marrow abnormalities. Rarely,
      radiation-induced malignancies may develop within the treatment field.
      Chemotherapy also influences posttreatment imaging appearance. Occasionally, it
      causes a substantial increase in tumor size that is a result of chemotherapy
      induced hemorrhage. Although myocutaneous flaps used in reconstructive surgery
      may mimic a mass, they demonstrate time-dependent changes in size, signal
      intensity, and enhancement on MR images. Recurrent tumor is characterized by the
      presence of a discrete nodule or mass with signal characteristics that typically
      mirror those of the original tumor. MR imaging sequences such as unenhanced T1
      weighted fat-suppressed and gradient-echo sequences may help differentiate
      posttreatment hemorrhage from local tumor recurrence. A consistent imaging
      approach combined with a detailed knowledge of the patient's history, familiarity
      with pretreatment images, and an understanding of the various posttreatment
      changes enables optimal monitoring of the treatment bed and maximizes accuracy in
      the detection of recurrence.

PMID- 19168841
TI  - Pediatric skeletal trauma: use of multiplanar reformatted and three-dimensional
      64-row multidetector CT in the emergency department.
AB  - Orthopedic injuries account for one-half of all emergency department visits by
      pediatric patients in the United States. Although radiography is the first-line
      method of diagnosis in the emergency department, multidetector computed
      tomography (CT) is playing an increasingly important role in definition of
      skeletal and soft-tissue injuries in the pediatric trauma patient. With the
      advent of 64-detector row CT, images can be produced with subsecond gantry
      rotation times and with submillimeter acquisition, which yield true isotropic
      high-resolution volume data sets. This technique is particularly advantageous in
      the evaluation of pediatric patients because it may eliminate the need for
      sedation and minimize dependence on patient cooperation. The role of three
      dimensional volume imaging in the evaluation of fractures and soft-tissue
      injuries in pediatric patients continues to evolve as this technique increasingly
      enables detection and characterization of abnormalities and provides results that
      affect decisions about patient care.

PMID- 19168842
TI  - Detection of vascular injuries in patients with blunt pelvic trauma by using 64
      channel multidetector CT.
AB  - Vascular injuries are a major source of morbidity and mortality in patients with
      blunt pelvic trauma. Digital subtraction angiography (DSA) has traditionally been
      used to detect pelvic arterial injuries and to treat active arterial hemorrhage.
      Improvements in the technology of computed tomography (CT) have facilitated the
      implementation of CT angiography, which is beginning to replace DSA in the
      evaluation of patients with acute trauma. Pelvic CT angiography can reliably
      depict various pelvic arterial injuries and can help differentiate arterial
      hemorrhage from venous hemorrhage on the basis of multiphasic acquisitions, a
      method that may be used to tailor the subsequent clinical approach. With the use
      of a 64-channel multidetector CT scanner, multiphasic pelvic CT angiography can
      be integrated into the evaluation of trauma patients by using 1.25-mm
      reconstructed section thickness, pitch of 1:0.987, and gantry revolution time of
      0.5 second to achieve near-isotropic results. A standard dose of 100 mL
      intravenous contrast material is injected at a rate of 5 mL/sec, and 30 mL saline
      solution, also at 5 mL/sec, is injected as a "chasing" bolus to follow the
      contrast material.

PMID- 19168843
TI  - Invasive lobular carcinoma of the breast: spectrum of mammographic, US, and MR
      imaging findings.
AB  - The reported prevalence of invasive lobular carcinoma (ILC) is variable, with
      more recent studies indicating that ILC accounts for 10%-15% of all invasive
      breast carcinomas. However, the radiologic diagnosis and management of ILC can be
      uniquely challenging. Current imaging modalities are not very specific for
      differentiating ILC from other invasive breast cancers, and ILC has a tendency to
      have appearances at mammography that are atypical for invasive ductal carcinomas,
      resulting in higher false-negative rates. The clinical detection of ILC can also
      be difficult, since ILC frequently fails to form a palpable lesion. This tendency
      of ILC to have atypical imaging and clinical appearances is related to its
      histopathologic features and its failure to elicit a desmoplastic response.
      Despite these diagnostic challenges, however, imaging remains crucial in the
      detection and management of ILC. Mammography, ultrasonography (US), and magnetic
      resonance (MR) imaging all play important roles, with each modality having its
      own advantages and limitations. The use of US and MR imaging as adjuncts to
      mammography increases sensitivity in the detection of ILC and provides useful
      information for further management and presurgical planning. Familiarity with the
      spectrum of imaging appearances of ILC is essential.

PMID- 19168844
TI  - Failed endoscopic sinus surgery: spectrum of CT findings in the frontal recess.
AB  - Since its introduction over 2 decades ago, functional endoscopic sinus surgery
      (FESS) has revolutionized the surgical management of chronic sinusitis. Performed
      over 200,000 times annually in the United States to treat medically refractory
      sinusitis, FESS has success rates as high as 98%. When surgical failure occurs,
      it is typically due to postoperative scarring or unaddressed outflow tract
      obstruction in the region of the frontal recess. The most common causes of
      surgical failure in the frontal recess include remnant frontal recess cells, a
      retained uncinate process, middle turbinate lateralization, osteoneogenesis,
      scarring or inflammatory mucosal thickening, and recurrent polyposis. Computed
      tomography (CT) of the paranasal sinuses has become indispensable in evaluation
      of patients with FESS failure, particularly in the frontal recess, a location
      that can be difficult to visualize at endoscopy. Familiarity with the complex
      anatomy of the frontal recess and knowledge of the most common causes of surgical
      failure are essential for proper interpretation of sinus CT images obtained in
      patients being considered for revision FESS of the frontal sinus.

PMID- 19168845
TI  - Aortoenteric fistulas: CT features and potential mimics.
AB  - Prompt diagnosis of aortoenteric fistulas is imperative for patient survival. The
      clinical signs of aortoenteric fistula include hematemesis, melena, sepsis, and
      abdominal pain, but the condition also may be clinically occult. Because clinical
      signs may not be present or may not be sufficiently specific, imaging is most
      often necessary to achieve an accurate diagnosis. Although no single imaging
      modality demonstrates the condition with sufficient sensitivity and specificity,
      computed tomography (CT), owing to its widespread availability and high
      efficiency, has become the imaging modality of choice for evaluations in the
      emergency setting. CT has widely variable sensitivity (40%-90%) and specificity
      (33%-100%) for the diagnosis of aortoenteric fistulas. To use this modality
      effectively for the initial diagnostic examination, radiologists must be familiar
      with the spectrum of CT appearances. Mimics of aortoenteric fistulas include
      retroperitoneal fibrosis, infected aortic aneurysm, infectious aortitis, and
      perigraft infection without fistulization. Differentiation is aided by the
      observation of ectopic gas, loss of the normal fat plane, extravasation of aortic
      contrast material into the enteric lumen, or leakage of enteric contrast material
      into the paraprosthetic space; these features are highly suggestive of
      aortoenteric fistula in a patient with bleeding in the gastrointestinal tract.

PMID- 19168846
TI  - Benign hepatic tumors and iatrogenic pseudotumors.
AB  - Myriad benign tumors may be found in the liver; they can be classified according
      to their cell of origin into tumors of hepatocellular, cholangiocellular, or
      mesenchymal origin. Common benign hepatic tumors may pose a diagnostic dilemma
      when they manifest with atypical imaging features. Less frequently encountered
      benign hepatic tumors such as inflammatory pseudotumor or biliary cystadenoma
      demonstrate less specific imaging features; however, awareness of their findings
      is useful in narrowing differential diagnostic considerations. In addition,
      certain iatrogenically induced abnormalities of the liver may be confused with
      more ominous findings such as infection or neoplasia. However, knowledge of their
      common imaging appearances, in addition to the clinical history, is critical in
      correctly diagnosing and characterizing iatrogenic abnormalities of the liver.
      Familiarity with both expected and unexpected imaging appearances of common
      benign hepatic tumors, less commonly encountered benign hepatic tumors, and
      iatrogenic abnormalities potentially masquerading as hepatic tumors allows the
      radiologist to achieve an informed differential diagnosis.

PMID- 19168847
TI  - Fatty liver disease: MR imaging techniques for the detection and quantification
      of liver steatosis.
AB  - Fatty liver disease is the most common cause of chronic liver disease in the
      United States. Noninvasive detection and quantification of fat is becoming more
      and more important clinically, due in large part to the growing prevalence of
      nonalcoholic fatty liver disease. Steatosis, the accumulation of fat-containing
      vacuoles within hepatocytes, is a key histologic feature of fatty liver disease.
      Liver biopsy, the current standard of reference for the assessment of steatosis,
      is invasive, has sampling errors, and is not appropriate in some settings.
      Several magnetic resonance (MR) imaging-based techniques--including chemical
      shift imaging, frequency-selective imaging, and MR spectroscopy--are currently in
      clinical use for the detection and quantification of fat-water admixtures, with
      each technique having important advantages, disadvantages, and limitations. These
      techniques permit the breakdown of the net MR signal into fat and water signal
      components, allowing the quantification of fat in liver tissue, and are
      increasingly being used in the diagnosis, treatment, and follow-up of fatty liver
      disease.

PMID- 19168848
TI  - Fat-containing lesions of the retroperitoneum: radiologic-pathologic correlation.
AB  - Retroperitoneal lesions represent a broad, diverse collection of entities; when
      they contain fat, the differential diagnosis, which ranges from benign to fully
      malignant lesions, substantially narrows. Lipomas rarely occur in the
      retroperitoneum; thus, fat-containing lesions in this location should never be
      dismissed as lipoma. Pelvic lipomatosis is the overgrowth of histologically
      normal fat in the extraabdominal compartments of the pelvis along the perirectal
      and perivesicular spaces. Infants and young children develop lipoblastomas rather
      than liposarcomas, which occur in older patients. Liposarcomas typically occur in
      patients 50-70 years old and manifest in multiple subtypes, with the most common
      being well-differentiated liposarcoma. Liposarcomas are histologically and
      radiologically protean, with no one imaging feature specific across the spectrum
      of subtypes. Hibernoma is a rare benign soft-tissue tumor composed of brown fat.
      Because hibernomas contain varied portions of brown and white fat as well as
      lesser amounts of myxoid material and spindle cells, their imaging features vary
      considerably. Teratomas are neoplasms that originate in pluripotent cells--benign
      or malignant germ cells--that give rise to a wide spectrum of mature or immature
      tissues that are foreign to the location in which they arise and which
      demonstrate varying amounts of organ formation. Myelolipoma, a benign tumor
      composed of mature fat and interspersed hematopoietic elements that resemble bone
      marrow, typically originate in an otherwise normal adrenal gland. Angiomyolipoma
      is composed of varying admixtures of blood vessels, smooth muscle cells, and
      adipose tissue; any one or two of these elements may predominate. Although these
      fat-containing lesions have overlapping radiologic features, use of demographic
      and clinical data helps refine the diagnostic options and treatment.

PMID- 19168849
TI  - Melanoma of the gallbladder.

PMID- 19168850
TI  - Menetrier disease.

PMID- 19168852
TI  - Germline CDH1 deletions in hereditary diffuse gastric cancer families.
AB  - Germline CDH1 point or small frameshift mutations can be identified in 30-50% of
      hereditary diffuse gastric cancer (HDGC) families. We hypothesized that CDH1
      genomic rearrangements would be found in HDGC and identified 160 families with
      either two gastric cancers in first-degree relatives and with at least one
      diffuse gastric cancer (DGC) diagnosed before age 50, or three or more DGC in
      close relatives diagnosed at any age. Sixty-seven carried germline CDH1 point or
      small frameshift mutations. We screened germline DNA from the 93 mutation
      negative probands for large genomic rearrangements by Multiplex Ligation
      Dependent Probe Amplification. Potential deletions were validated by RT-PCR and
      breakpoints cloned using a combination of oligo-CGH-arrays and long-range-PCR. In
      silico analysis of the CDH1 locus was used to determine a potential mechanism for
      these rearrangements. Six of 93 (6.5%) previously described mutation negative
      HDGC probands, from low GC incidence populations (UK and North America), carried
      genomic deletions (UK and North America). Two families carried an identical
      deletion spanning 193 593 bp, encompassing the full CDH3 sequence and CDH1 exons
      1 and 2. Other deletions affecting exons 1, 2, 15 and/or 16 were identified. The
      statistically significant over-representation of Alus around breakpoints
      indicates it as a likely mechanism for these deletions. When all mutations and
      deletions are considered, the overall frequency of CDH1 alterations in HDGC is
      approximately 46% (73/160). CDH1 large deletions occur in 4% of HDGC families by
      mechanisms involving mainly non-allelic homologous recombination in Alu repeat
      sequences. As the finding of pathogenic CDH1 mutations is useful for management
      of HDGC families, screening for deletions should be offered to at-risk families.

PMID- 19168853
TI  - Gigaxonin controls vimentin organization through a tubulin chaperone-independent
      pathway.
AB  - Gigaxonin mutations cause the fatal human neurodegenerative disorder giant axonal
      neuropathy (GAN). Broad deterioration of the nervous system in GAN patients is
      accompanied by massive disorganization of intermediate filaments (IFs) both in
      neurons and many non-neuronal cells. With newly developed antibodies, gigaxonin
      is now shown to be expressed at extremely low levels throughout the nervous
      system. In lymphoblast cell lines derived from severe and mild forms of GAN,
      mutations in gigaxonin are shown to yield highly unstable proteins, thereby
      permitting a rapid diagnostic test for the spectrum of GAN mutations as an
      alternative to invasive nerve biopsy or systematic sequencing of the GAN gene.
      Gigaxonin has been proposed as a substrate adaptor for an E3 ubiquitin ligase,
      which affects proteasome-dependent degradation of microtubule-related proteins
      including MAP1B, MAP8 and the tubulin folding chaperone TBCB. We demonstrate
      that, unlike its counterpart TBCE, TBCB only moderately destabilizes
      microtubules. Neither TBCB abundance nor microtubule organization or densities
      are altered in GAN mutant fibroblasts, thus demonstrating that altered TBCB
      levels are not primary determinants of IF disorganization in GAN. Characteristic
      GAN mutant-induced ovoid aggregates of vimentin are not produced in normal
      fibroblasts after disrupting microtubule assembly, either by TBCE overexpression
      or depolymerizing drugs. Thus, IF disorganization in GAN fibroblasts is
      independent of TBCB and microtubule loss and must be regulated by a yet
      unidentified mechanism.

PMID- 19168854
TI  - Parathyroid hormone improves contractile performance of adult rat ventricular
      cardiomyocytes at low concentrations in a non-acute way.
AB  - AIMS: In patients with congestive heart failure, plasma parathyroid hormone (PTH)
      levels are positively associated with cardiac function. PTH, used to mobilize
      stem cells from the bone marrow after myocardial infarction, causes an increased
      left ventricular ejection fraction. The aim of this study was to investigate
      whether low but plasma-relevant concentrations of PTH directly influence the
      contractile properties of cardiomyocytes. METHODS AND RESULTS: Isolated adult rat
      ventricular cardiomyocytes were exposed to PTH(1-34) or full-length PTH at
      picomolar concentrations for 24 h. Cell shortening was measured at 2 Hz as a
      cellular correlate of inotropic responsiveness. Intracellular calcium was
      measured in Fura-AM-loaded cells. PTH(1-3) (20-200 pM) and full-length PTH (200
      pM) increased cell shortening within 24 h. PTH had no effect on cell size, but
      resting and peak systolic calcium concentrations were elevated. The beneficial
      effect of PTH was mediated via its cAMP/protein kinase A-activating domain and
      attenuated by addition of a protein kinase A inhibitor. In contrast, PTH peptides
      representing a protein kinase C-activating domain but not a cAMP/protein kinase A
      activating domain or peptides that represent none of these domains had no effect
      on cell shortening. The effect of PTH on cell shortening was strong at low
      concentrations of extracellular calcium but declined at higher calcium
      concentrations. PTH downregulated the expression of the calcium sensing receptor,
      a receptor known to antagonize the action of PTH on calcium transport.
      Furthermore, PTH antagonized the angiotensin II-induced loss of cell function.
      CONCLUSION: Low concentrations of PTH improve cell shortening by increasing
      calcium load at rest. By this mechanism cardiomyocytes compensate reduced
      extracellular calcium levels as they occur in patients with heart failure.

PMID- 19168855
TI  - Protein kinase C in heart failure: a therapeutic target?
AB  - Heart failure (HF) afflicts about 5 million people and causes 300,000 deaths a
      year in the United States alone. An integral part of the pathogenesis of HF is
      cardiac remodelling, and the signalling events that regulate it are a subject of
      intense research. Cardiac remodelling is the sum of responses of the heart to
      causes of HF, such as ischaemia, myocardial infarction, volume and pressure
      overload, infection, inflammation, and mechanical injury. These responses,
      including cardiomyocyte hypertrophy, myocardial fibrosis, and inflammation,
      involve numerous cellular and structural changes and ultimately result in a
      progressive decline in cardiac performance. Pharmacological and genetic
      manipulation of cultured heart cells and animal models of HF and the analysis of
      cardiac samples from patients with HF are all used to identify the molecular and
      cellular mechanisms leading to the disease. Protein kinase C (PKC) isozymes, a
      family of serine-threonine protein kinase enzymes, were found to regulate a
      number of cardiac responses, including those associated with HF. In this review,
      we describe the PKC isozymes that play critical roles in specific aspects of
      cardiac remodelling and dysfunction in HF.

PMID- 19168857
TI  - Advance of age decreases the minimum alveolar concentrations of isoflurane and
      sevoflurane for maintaining bispectral index below 50.
AB  - BACKGROUND: We investigated age-related differences in the minimum alveolar
      concentration (MAC) of isoflurane and sevoflurane for maintaining bispectral
      index (BIS) below 50 (MAC(BIS50)). METHODS: One hundred and twenty young (<or=40
      yr), middle-aged (41-69 yr), and elderly (>or=70 yr) patients were randomly
      allocated to one of the six groups. Anaesthesia was induced with isoflurane or
      sevoflurane in oxygen. After tracheal intubation, we arbitrarily started
      maintenance of anaesthesia in each group with end-tidal isoflurane and
      sevoflurane concentrations of 0.8 and 1.2 vol%, respectively. After 10 min at
      predetermined end-tidal isoflurane or sevoflurane concentrations, BIS was
      measured for 1 min. MAC(BIS50) of isoflurane or sevoflurane for each group was
      determined by up-down methodology. RESULTS: MAC(BIS50) of isoflurane in young,
      middle-aged, and elderly patients was 0.82% end-tidal (95% confidence intervals
      0.76-0.88), 0.67% (0.61-0.73), and 0.56% (0.51-0.61), respectively, and that of
      sevoflurane in young, middle-aged, and elderly patients was 1.28% (1.24-1.32),
      0.97% (0.89-1.05), and 0.87% (0.84-0.90), respectively. For both isoflurane and
      sevoflurane, the MAC(BIS50) was significantly higher (P=0.002 and 0.001,
      respectively) in young patients and significantly lower (P=0.02 for both) in
      elderly patients than those in middle-aged patients. CONCLUSIONS: Advance in age
      significantly decreased the concentrations of isoflurane and sevoflurane required
      to maintain BIS below 50. BIS correctly reflected age-associated decrease of end
      tidal concentrations of isoflurane and sevoflurane required for maintaining
      adequate depth of anaesthesia during resting state.

PMID- 19168856
TI  - Prothrombin complex concentrate vs fresh frozen plasma for reversal of dilutional
      coagulopathy in a porcine trauma model.
AB  - BACKGROUND: Fluid resuscitation following traumatic injury causes haemodilution
      and can contribute to coagulopathy. Coagulation factor replacement may be
      necessary to prevent bleeding complications of dilutional coagulopathy. Compared
      with fresh frozen plasma (FFP), prothrombin complex concentrate (PCC) may
      potentially offer a more rapid and effective means of normalizing coagulation
      factor levels. METHODS: In anaesthetized mildly hypothermic pigs, 65-70% of total
      blood volume was substituted in phases with hydroxyethyl starch and red cells.
      Animals were then treated with 15 ml kg(-1) isotonic saline placebo, 25 IU kg(-1)
      PCC, or 15 ml kg(-1) FFP. Immediately thereafter, either a standardized femur or
      spleen injury was inflicted, and coagulation function, including thrombin
      generation, and bleeding were assessed. An additional group received high-dose
      FFP (40 ml kg(-1)) before femur injury. RESULTS: Haemodilution markedly prolonged
      prothrombin time and reduced peak thrombin generation. PCC, but not FFP, fully
      reversed those effects. Compared with 15 ml kg(-1) FFP, PCC shortened the time to
      haemostasis after either bone (P=0.001) or spleen (P=0.028) trauma and reduced
      the volume of blood lost (P<0.001 and P=0.015, respectively). Subsequent to bone
      injury, PCC also accelerated haemostasis (P=0.003) and diminished blood loss
      (P=0.006) vs 40 ml kg(-1) FFP. CONCLUSIONS: PCC was effective in correcting
      dilutional coagulopathy and controlling bleeding in an in vivo large-animal
      trauma model. In light of its suitability for more rapid administration than FFP,
      PCC merits further investigation as a therapy for dilutional coagulopathy in
      trauma and surgery.

PMID- 19168858
TI  - Targeted endomyocardial biopsy using electroanatomical voltage mapping in the
      early stage of arrhythmogenic right ventricular cardiomyopathy.
AB  - Endomyocardial biopsy (EMB) is useful for making a diagnosis of cardiomyopathy.
      However, the sensitivity of conventional EMB specimens from the interventricular
      septum is low in arrhythmogenic right ventricular cardiomyopathy (ARVC),
      especially in the early stage, because of the limited location of the affected
      tissue. Therefore, it is important to be able to target only the affected tissue
      in order to improve the sensitivity of the EMB, especially in the early stage of
      ARVC. A significant correlation between the low voltage areas identified by the
      electroanatomical voltage mapping (EVM) and abnormal findings from the EMB in
      ARVC has been reported. We describe an innovative strategy for performing EMB,
      using EVM to identify the local affected area and to perform a selective EMB from
      that area.

PMID- 19168859
TI  - Lead malfunctions in implantable cardioverter defibrillators: where are we and
      where should we go?

PMID- 19168860
TI  - Genome size diversity in orchids: consequences and evolution.
AB  - BACKGROUND: The amount of DNA comprising the genome of an organism (its genome
      size) varies a remarkable 40 000-fold across eukaryotes, yet most groups are
      characterized by much narrower ranges (e.g. 14-fold in gymnosperms, 3- to 4-fold
      in mammals). Angiosperms stand out as one of the most variable groups with genome
      sizes varying nearly 2000-fold. Nevertheless within angiosperms the majority of
      families are characterized by genomes which are small and vary little. Species
      with large genomes are mostly restricted to a few monocots families including
      Orchidaceae. SCOPE: A survey of the literature revealed that genome size data for
      Orchidaceae are comparatively rare representing just 327 species. Nevertheless
      they reveal that Orchidaceae are currently the most variable angiosperm family
      with genome sizes ranging 168-fold (1C = 0.33-55.4 pg). Analysing the data
      provided insights into the distribution, evolution and possible consequences to
      the plant of this genome size diversity. CONCLUSIONS: Superimposing the data onto
      the increasingly robust phylogenetic tree of Orchidaceae revealed how different
      subfamilies were characterized by distinct genome size profiles. Epidendroideae
      possessed the greatest range of genome sizes, although the majority of species
      had small genomes. In contrast, the largest genomes were found in subfamilies
      Cypripedioideae and Vanilloideae. Genome size evolution within this subfamily was
      analysed as this is the only one with reasonable representation of data. This
      approach highlighted striking differences in genome size and karyotype evolution
      between the closely related Cypripedium, Paphiopedilum and Phragmipedium. As to
      the consequences of genome size diversity, various studies revealed that this has
      both practical (e.g. application of genetic fingerprinting techniques) and
      biological consequences (e.g. affecting where and when an orchid may grow) and
      emphasizes the importance of obtaining further genome size data given the
      considerable phylogenetic gaps which have been highlighted by the current study.

PMID- 19168861
TI  - Biodiversity effects on yield and unsown species invasion in a temperate forage
      ecosystem.
AB  - BACKGROUND AND AIMS: Current agricultural practices are based on growing
      monocultures or binary mixtures over large areas, with a resultant impoverishing
      effect on biodiversity at several trophic levels. The effects of increasing the
      biodiversity of a sward mixture on dry matter yield and unsown species invasion
      were studied. METHODS: A field experiment involving four grassland species [two
      grasses--perennial ryegrass (Lolium perenne) and cocksfoot (Dactylis glomerata)-
      and two legumes--red clover (Trifolium pratense) and white clover (Trifolium
      repens)], grown in monocultures and mixtures in accordance with a simplex design,
      was carried out. The legumes were included either as single varieties or as one
      of two broad genetic-base composites. The experiment was harvested three times a
      year over three years; dry matter yield and yield of unsown species were
      determined at each harvest. Yields of individual species and interactions between
      all species present were estimated through a statistical modelling approach. KEY
      RESULTS: Species diversity produced a strong positive yield effect that resulted
      in transgressive over-yielding in the second and third years. Using broad genetic
      base composites of the legumes had a small impact on yield and species
      interactions. Invasion by unsown species was strongly reduced by species
      diversity, but species identity was also important. Cocksfoot and white clover
      (with the exception of one broad genetic-base composite) reduced invasion, while
      red clover was the most invaded species. CONCLUSIONS: The results show that it is
      possible to increase, and stabilize, the yield of a grassland crop and reduce
      invasion by unsown species by increasing its species diversity.

PMID- 19168862
TI  - The effects of luteinizing hormone ablation/replacement versus steroid
      ablation/replacement on gene expression in the primate corpus luteum.
AB  - This study was designed to provide a genome-wide analysis of the effects of
      luteinizing hormone (LH) versus steroid ablation/replacement on gene expression
      in the developed corpus luteum (CL) in primates during the menstrual cycle. On
      Days 9-11 of the luteal phase, female rhesus monkeys were left untreated
      (control) or received a GnRH antagonist Antide (A), A + LH, A + LH + the 3beta
      hydroxysteroid dehydrogenase inhibitor Trilostane (TRL) or A + LH + TRL + a
      progestin R5020. On Day 12 of the luteal phase, CL were removed and samples of
      RNA from individual CL were hybridized to Affymetrix rhesus macaque total genome
      microarrays. The greatest number of altered transcripts was associated with the
      ablation/replacement of LH, while steroid ablation/progestin replacement affected
      fewer transcripts. Replacement of LH during Antide treatment restored the
      expression of most transcripts to control levels. Validation of a subset of
      transcripts revealed that the expression patterns were similar between microarray
      and real-time PCR. Analyses of protein levels were subsequently determined for
      two transcripts. This is the first genome-wide analysis of LH and steroid
      regulation of gene transcription in the developed primate CL. Further analysis of
      novel transcripts identified in this data set can clarify the relative role for
      LH and steroids in CL maintenance and luteolysis.

PMID- 19168863
TI  - Pharmacokinetic parameters of artesunate and dihydroartemisinin in rats infected
      with Fasciola hepatica.
AB  - OBJECTIVES: The pharmacokinetic (PK) parameters of artesunate, recently
      discovered to possess promising trematocidal activity, and its main metabolite
      dihydroartemisinin (DHA) were determined in rats infected with hepatic and
      biliary stages of Fasciola hepatica and compared with uninfected rats after
      single intragastric and intravenous (iv) doses. METHODS: Rats infected with F.
      hepatica for 25 and 83 days and uninfected rats were cannulated in the right
      jugular vein and blood samples were withdrawn at selected timepoints following 10
      mg/kg of iv and a single 100 mg/kg oral dose of artesunate. Plasma was analysed
      for artesunate and DHA by liquid chromatography coupled to tandem mass
      spectrometry. RESULTS: Rats harbouring juvenile and adult F. hepatica infections
      revealed considerable changes in PK parameters of artesunate and DHA. Following
      oral administration, maximum plasma concentrations (C(max)) of artesunate and DHA
      were 1.8-2.3-fold higher in infected rats [artesunate: 1334 +/- 1404 ng/mL (no
      infection) versus 2454 +/- 1494 ng/mL (acute infection) and 2768 +/- 538 ng/mL
      (chronic infection); DHA: 3802 +/- 2149 ng/mL (no infection) versus 6507 +/- 3283
      ng/mL (acute infection) and 9093 +/- 884 ng/mL (chronic infection)]. The AUCs of
      artesunate and DHA were 2.1-4.4-fold greater in infected rats. An opposite trend
      was observed after iv injection. C(max) and AUC of artesunate and DHA following
      iv dosing were 5784 +/- 3718 and 140 938 +/- 128 783 ng.min/mL and 3849 +/- 3060
      and 86 107 +/- 41 863 ng.min/mL, respectively, in uninfected rats versus 2623 +/-
      1554 and 21 617 +/- 12 230 ng.min/mL and 2835 +/- 980 and 64 290 +/- 29 057
      ng.min/mL, respectively, in rats harbouring a chronic infection. The elimination
      half-lives (t(1/2)) of artesunate and DHA were considerably altered in infected
      rats following oral and iv administration of artesunate. CONCLUSIONS: F. hepatica
      infections strongly influence the disposition kinetics of artesunate and its
      metabolite in rats. The clinical implications of this finding need to be
      carefully studied.

PMID- 19168864
TI  - Efficacy of oral and intraperitoneal administration of CBMIDA for removing
      uranium in rats after parenteral injections of depleted uranium.
AB  - The efficacy of oral administration of the chelating agent catechol-3,6
      bis(methyleiminodiacetic acid) (CBMIDA) for removing uranium from rats after
      intraperitoneal (i.p.) and intramuscular (i.m.) injections of depleted uranium
      (DU) was examined and the results with those by the i.p. injection of CBMIDA were
      compared. In Experiment 1, after a single i.p. injection of 8 mg kg(-1) of DU of
      rat's body weight, 35 8-week-old male rats were divided into seven groups
      consisting of five rats each. Three groups were administered with CBMIDA 240, 720
      or 1200 mg kg(-1) of rat's body weight orally once a day, and three other groups
      received an i.p. injection of 240, 480 or 720 mg kg(-1) CBMIDA for 3 d, starting
      30 min after DU injection on the first day. One DU group received no CBMIDA. The
      remaining five intact rats were used as a control group. Rats were killed 6 d
      after DU injection. In Experiment 2, the 35 male rats that received a single i.m.
      injection of 8 mg kg(-1) DU were divided into seven groups, and the rats of each
      group received the same doses of CBMIDA on the same schedules of treatment as
      those described in Experiment 1. The results obtained in Experiment 1 indicated
      that orally administered CBMIDA significantly increased the excretion of uranium
      at doses of 720 and 1200 mg kg(-1) and decreased uranium concentrations,
      particularly in the kidney, at all the doses tested, and the effects were almost
      equal to those of the i.p. injection. The lack of increases in creatinine and
      blood urea nitrogen in serum indicated that CBMIDA is efficacious in preventing
      the renal dysfunction caused by uranium. In Experiment 2, oral administration of
      CBMIDA significantly increased uranium excretion and significantly decreased
      uranium concentrations, particularly in the kidneys, at all the doses tested, and
      the effects were almost equal to those of the i.p. injection. However, these
      effects of CBMIDA on the i.m.-injected DU were lower than those of the i.p.
      injected DU in Experiment 1. These results indicated that oral administration of
      CBMIDA has almost the same efficacy as that administered by the parenteral route.
      Additional study is necessary to obtain satisfactory effects for the clinical use
      of CBMIDA, particularly for wounds contaminated accidentally with uranium.

PMID- 19168865
TI  - Targeted deletion of nuclear factor kappaB p50 enhances cardiac remodeling and
      dysfunction following myocardial infarction.
AB  - Myocardial infarction is commonly complicated by left ventricular remodeling, a
      process that leads to cardiac dilatation, congestive heart failure and death. The
      innate immune system plays a pivotal role in the remodeling process via nuclear
      factor (NF)-kappaB activation. The NF-kappaB transcription factor family includes
      several subunits (p50, p52, p65, c-Rel, and Rel B) that respond to myocardial
      ischemia. The function of NF-kappaB p50, however, is controversial in this
      process. To clarify the role of NF-kappaB p50 in postinfarct left ventricular
      remodeling, myocardial infarction was induced in wild-type 129Bl6 mice and NF
      kappaB p50-deficient mice. Without affecting infarct size, deletion of NF-kappaB
      p50 markedly increased the extent of expansive remodeling (end-diastolic volume:
      176+/-13 microL versus 107+/-11 microL; P=0.003) and aggravated systolic
      dysfunction (left ventricular ejection fraction: 16.1+/-1.5% versus 24.7+/-3.7%;
      P=0.029) in a 28-day time period. Interstitial fibrosis and hypertrophy in the
      noninfarcted myocardium was increased in NF-kappaB p50 knockout mice. In the
      infarct area, a lower collagen density was observed, which was accompanied by an
      increased number of macrophages, higher gelatinase activity and increased
      inflammatory cytokine expression. In conclusion, targeted deletion of NF-kappaB
      p50 results in enhanced cardiac remodeling and functional deterioration following
      myocardial infarction by increasing matrix remodeling and inflammation.

PMID- 19168866
TI  - Peak treadmill exercise echocardiography: not feasible?

PMID- 19168867
TI  - Real-time three-dimensional transoesophageal echocardiography for guidance of
      interventional closure of paravalvular leakage.

PMID- 19168868
TI  - Computer-assisted myocardial blush quantification after percutaneous coronary
      angioplasty for acute myocardial infarction: a substudy from the TAPAS trial.
AB  - AIMS: Myocardial reperfusion after acute myocardial infarction can be
      angiographically assessed by the myocardial blush grade (MBG) or TIMI Perfusion
      Grade. These scores are based on subjective human judgement and lead to a score
      of four categories. A more operator-independent way of scoring myocardial
      perfusion may facilitate research in this area. METHODS AND RESULTS: We designed
      the 'Quantitative Blush Evaluator' (QuBE), a computer program which calculates a
      score for myocardial perfusion. This program will be freely available as open
      source software. The inter-observer concordance was 97.7%. We calculated values
      on prospectively collected angiograms in patients with acute ST-elevation
      myocardial infarction from the TAPAS trial. Quantitative blush evaluator values
      could be assessed on 790 out of 980 collected angiograms (81%). The QuBE score
      correlated significantly with MBG as determined by a core lab. The QuBE score
      predicted complete ST-elevation resolution, low enzyme levels, and 1 year
      survival (all P < 0.001). Quantitative blush evaluator value was an independent
      predictor of mortality at 1 year [OR 0.40 (0.17-0.90), P = 0.02]. CONCLUSION: The
      QuBE program provides a practical, freely available computer-assisted assessment
      of myocardial perfusion. The QuBE score provides a useful surrogate endpoint in
      trials of therapies aimed at improving myocardial reperfusion.

PMID- 19168869
TI  - Myocarditis by mesalazine with cardiac magnetic resonance imaging.

PMID- 19168870
TI  - The effects of aetiology on outcome in patients treated with cardiac
      resynchronization therapy in the CARE-HF trial.
AB  - AIMS: Cardiac dyssynchrony is common in patients with heart failure, whether or
      not they have ischaemic heart disease (IHD). The effect of the underlying cause
      of cardiac dysfunction on the response to cardiac resynchronization therapy (CRT)
      is unknown. This issue was addressed using data from the CARE-HF trial. METHODS
      AND RESULTS: Patients (n = 813) were grouped by heart failure aetiology (IHD n =
      339 vs. non-IHD n = 473), and the primary composite (all-cause mortality or
      unplanned hospitalization for a major cardiovascular event) and principal
      secondary (all-cause mortality) endpoints analysed. Heart failure severity and
      the degree of dyssynchrony were compared between the groups by analysing baseline
      clinical and echocardiographic variables. Patients with IHD were more likely to
      be in NYHA class IV (7.5 vs. 4.0%; P = 0.03) and to have higher NT-proBNP levels
      (2182 vs. 1725 pg/L), indicating more advanced heart failure. The degree of
      dyssynchrony was more pronounced in patients without IHD (assessed using mean QRS
      duration, interventricular mechanical delay, and aorta-pulmonary pre-ejection
      time). Left ventricular ejection fraction and left ventricular end-systolic
      volume improved to a lesser extent in the IHD group (4.53 vs. 8.50% and -35.68
      vs. -58.52 cm(3)). Despite these differences, CRT improved all-cause mortality,
      NYHA class, and hospitalization rates to a similar extent in patients with or
      without IHD. CONCLUSION: The benefits of CRT in patients with or without IHD were
      similar in relative terms in the CARE-HF study but as patients with IHD had a
      worse prognosis, the benefit in absolute terms may be greater.

PMID- 19168871
TI  - Molecular mechanisms of ovarian hyperstimulation syndrome: paracrine reduction of
      endothelial claudin 5 by hCG in vitro is associated with increased endothelial
      permeability.
AB  - BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially life
      threatening complication of ovarian stimulation associated with severe vascular
      hyperpermeability. Primary co-cultures of human luteinized granulosa cells (LGCs)
      and human umbilical vein endothelial cells (HUVECs) were used as a model of
      steroidgenic/endothelial cell interaction in OHSS. METHODS: hCG and the vascular
      endothelial growth factor (VEGF) inhibitor, Flt-1Fc, were added to co-cultures of
      LGCs and HUVECs separated by a micropore membrane. Endothelial permeability to
      labeled bovine serum albumin was measured and the expression of the endothelial
      cell-specific adhesion protein claudin 5 was investigated using
      immunocytochemistry and western blotting. RESULTS: The addition of hCG increased
      HUVEC permeability in the presence of LGCs (P < 0.05). hCG increased VEGF
      concentrations in both chambers of the co-culture system (P < 0.05). The
      increased permeability in the presence of LGCs and hCG was inhibited when VEGF
      was blocked by Flt-1Fc (P < 0.05). Endothelial membrane claudin 5 protein was
      reduced in the presence of hCG and LGCs, as measured by immunocytochemistry (P <
      0.05) and western blotting (P < 0.05) and this reduction was inhibited by Flt
      1Fc. hCG had no direct effects on endothelial cell claudin 5. CONCLUSIONS: For
      OHSS, this novel paradigm suggests that hCG can increase endothelial permeability
      by up-regulating VEGF in LGCs which causes reduction in endothelial claudin 5
      expression.

PMID- 19168872
TI  - Down-regulation of p21-activated kinase 1 by progestin and its increased
      expression in the eutopic endometrium of women with endometriosis.
AB  - BACKGROUND: P21-activated kinase 1 (Pak1) integrates various signaling pathways
      that are vital to cell survival and function. This study was performed to
      evaluate whether sex steroids may regulate the expression of Pak1 in endometrial
      cells as well as whether its expression is increased in the eutopic endometrium
      of women with endometriosis. METHODS: Following in vitro estradiol (E(2)) and/or
      medroxyprogesterone acetate (MPA) treatment of Ishikawa cells and endometrial
      stromal cells (ESCs), Pak1 protein was analyzed utilizing western blot analysis
      and immunocytochemistry. Immunohistochemistry was performed to evaluate Pak1
      immunoreactivity semiquantitatively in women with endometriosis and in controls.
      To assess the role of Pak1 on endometrial cell viability, crystal violet assay
      was performed following transfection of Ishikawa cells with Pak1 small
      interfering RNA (siRNA). RESULTS: In vitro treatment with E(2) plus MPA or MPA
      alone led to a significant decrease of Pak1 protein in Ishikawa cells and ESCs
      (both P < 0.05 versus control). Immunohistochemistry also revealed that Pak1
      protein is significantly decreased during the secretory phase in both epithelial
      and stromal cells in the control subjects (P < 0.001 and P < 0.01, respectively).
      The immunoreactivity of Pak1 in glandular cells was significantly increased in
      the eutopic endometrium of women with endometriosis compared with the controls
      during the secretory phase (P < 0.01). Crystal violet assay has shown that
      transfection of Ishikawa cells with Pak1 siRNA led to a significant decrease of
      cellular viability (P < 0.05). CONCLUSIONS: These findings suggest that Pak1 is
      down-regulated by progesterone during the secretory phase in normal endometrium
      and increased Pak1 activity during the secretory phase might lead to
      establishment of endometriosis.

PMID- 19168873
TI  - 'Not taken in by media hype': how potential donors, recipients and members of the
      general public perceive stem cell research.
AB  - BACKGROUND: Views of embryo donors, scientists and members of the general public
      on embryonic stem cell research (eSCR) have been widely reported. Less is known
      about views of potential beneficiaries of stem cell therapy and the influence of
      media 'hype' on perceptions of eSCR among different groups of stakeholders. This
      study aimed to examine the perceptions of members of the general public as well
      as two patient groups likely to benefit from eSCR and to explore the role of the
      media in shaping these views. METHODS: A qualitative study carried out in
      Aberdeen, Scotland included 15 people living with Parkinson's disease (PD), 15
      people living with diabetes mellitus (DM), 15 couples with infertility and 21
      members of the general public who volunteered for the study. Interview
      transcripts were analysed thematically using grounded theory. RESULTS: The two
      patient groups likely to benefit from eSCR in the future differed in their
      knowledge (mainly gained from the media) and understanding of eSCR. Those living
      with PD were older, more debilitated and better informed than those with DM who
      showed limited interest in potential future benefits of eSCR. Infertile couples
      learnt about eSCR from health professionals who explained the process of embryo
      donation to them, and had sought no further information. Most of the general
      public had accessed information on eSCR and believed themselves to be more
      discerning than others because of their objectivity, intelligence and 'scientific
      awareness'. Although, the media and internet were primary sources of information
      for all except couples with infertility, members of all four groups claimed not
      to be taken in by the media 'hype' surrounding eSCR. CONCLUSIONS: Those who
      expected to benefit from eSCR in the future as well as members of the general
      public differ in their susceptibility to media 'hype', while believing that they
      are not taken in by exaggerated claims of benefits. As respondents were a
      selected group who were not drawn from a representative sample, the findings
      cannot be generalized to a wider population.

PMID- 19168874
TI  - Long-term follow-up of patients with polycystic ovary syndrome: reproductive
      outcome and ovarian reserve.
AB  - BACKGROUND: The purpose of the present study was to examine long-term
      reproductive outcome and ovarian reserve in an unselected population of women
      with polycystic ovary syndrome (PCOS). METHODS A total of 91 patients with
      confirmed PCOS and 87 healthy controls were included in the study. Patients had
      been diagnosed between 1987 and 1995 and at the time of the follow-up, subjects
      were 35 years of age or older. RESULTS: Among women who had attempted a
      pregnancy, 86.7% of PCOS patients and 91.6% of controls had given birth to at
      least one child. Among PCOS patients who had given birth, 73.6% had done so
      following a spontaneous conception. Mean ovarian volume and the number of antral
      follicles in PCOS patients were significantly greater than in control women (P <
      0.001, respectively). PCOS patients also had higher serum concentrations of anti
      Mullerian hormone and lower follicle-stimulating hormone levels. CONCLUSIONS:
      Most women with PCOS had given birth, and the rate of spontaneous pregnancies was
      relatively high. Together with the ultrasound findings and the hormonal analyses,
      this finding could imply that PCOS patients have a good fecundity, and an ovarian
      reserve possibly superior to women with normal ovaries.

PMID- 19168875
TI  - Metastatic adrenocortical carcinoma treated with sunitinib: a case report.
AB  - Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis.
      Palliative chemotherapy can be considered in patients with metastatic disease.
      Although mitotane- or cisplatin-based chemotherapy regimens are widely used, the
      effects of these agents have been limited. We have experienced a case that showed
      a partial response with sunitinib after failure of mitotane-based cytotoxic
      chemotherapy. The clinical benefit from sunitinib persisted 7.5 months in this
      case. To our knowledge, this is the first reported case showing the effects of
      sunitinib on metastatic ACC.

PMID- 19168877
TI  - Reduction of time-varying nanotesla magnetic fields from electric power lines by
      twisting.
AB  - Time-varying magnetic fields generated by electrical power lines in the
      laboratory can disturb electron microscope imaging. Modern microscopes require
      these fields to be below 10 nT [2]. We calculated and measured magnetic fields
      from straight and twisted current-carrying wires, and show that without twisting,
      this value cannot be reached.

PMID- 19168876
TI  - Predictors of fatal and non-fatal outcomes in the Controlled Rosuvastatin
      Multinational Trial in Heart Failure (CORONA): incremental value of
      apolipoprotein A-1, high-sensitivity C-reactive peptide and N-terminal pro B-type
      natriuretic peptide.
AB  - AIMS: Few prognostic models in heart failure have been developed in typically
      elderly patients treated with modern pharmacological therapy and even fewer
      included simple biochemical tests (such as creatinine), new biomarkers (such as
      natriuretic peptides), or, especially, both. In addition, most models have been
      developed for the single outcome of all-cause mortality. METHODS AND RESULTS: We
      built a series of models for nine different fatal and non-fatal outcomes. For
      each outcome, a model was first built using demographic and clinical variables
      (Step 1), then with the addition of biochemical measures (serum creatinine,
      alanine aminotransferase, creatine kinase, thyrotrophin, apolipoproteins A-1 and
      B, and triglycerides) (Step 2) and finally with the incorporation of high
      sensitivity C-reactive protein (hsCRP) and N-terminal pro B-type natriuretic
      peptide (NT-proBNP). Ranked according to the Wald chi(2) value, age (56),
      ejection fraction (44), and body mass index (42) were most predictive of all
      cause mortality in Step 1 (total model chi(2) 343). Creatinine was the most
      powerful predictor at Step 2 (48) and ApoA-1 ranked fifth (25), with the overall
      chi(2) increasing to 440. Log NT-proBNP (167) was the most powerful of the 14
      independently predictive variables identified at Step 3 and the overall chi(2)
      increased to 600. NT-proBNP was the most powerful predictor of each other
      outcome. hsCRP was not a predictor of all-cause mortality but did predict the
      composite atherothrombotic outcome. CONCLUSION: Of the two new biomarkers studied
      in prognostic models in heart failure, NT-proBNP, but not hsCRP, added
      substantial and independent predictive information, for a range of clinical
      outcomes, to that provided by simple demographic, clinical, and biochemical
      measures. ApoA-1 was more predictive than LDL or HDL.

PMID- 19168878
TI  - Equine disease surveillance. Quarterly report July to September 2008.

PMID- 19168880
TI  - Effects of previous control programmes on the proportion of horses shedding small
      numbers of strongyle-type eggs.
AB  - Between 30 and 70 per cent of horses at 18 stables had their anthelmintic
      treatments withdrawn for a year. Three of the stables (group 1) had used no
      anthelmintics for many years, 10 (group 2) had treated their horses with
      anthelmintics approximately twice a year, and five (group 3) had used
      anthelmintics five to seven times a year. A total of 1068 samples of faeces were
      collected from the 267 untreated horses and faecal egg counts were carried out
      four times during the year. Overall 50.2 per cent of the samples contained less
      than 200 epg. When the four counts from individual horses were collated, 35.6 per
      cent of the horses were low egg-shedders (LES). However, the previous control
      programme had a marked effect on both the mean log(10) epg and the proportion of
      horses in the stables that were LES. The proportions of LES among the horses in
      the stables in groups 1 and 2 were similar, although the log(10) epg was
      significantly lower in group 2. There was a markedly higher proportion of LES and
      a lower mean log(10) epg in the untreated horses at the stables in group 3 than
      in either of the other groups. The horses at the stables in groups 2 and 3 that
      remained on the anthelmintic programme previously used at the stables had lower
      egg counts than the untreated horses at the same stables, but the difference was
      usually not statistically significant. At the stables in group 2 the proportions
      of horses that were LES in the treated and untreated groups were not
      significantly different. At the stables in group 3 the proportion of LES was
      significantly lower in the treated horses than in the untreated horses.

PMID- 19168881
TI  - PCR survey of vectorborne pathogens in dogs living in and around Barcelona, an
      area endemic for leishmaniasis.
AB  - Blood samples from 153 dogs living in and around Barcelona were assayed for
      Leishmania infantum and Ehrlichia, Anaplasma, Rickettsia, Bartonella, Hepatozoon,
      Babesia and Theileria species by PCR amplification of DNA, and the amplicons
      obtained were sequenced. The prevalence of the infectious agents was L infantum
      (29.4 per cent), Ehrlichia and Anaplasma species (4.0 per cent), Hepatozoon canis
      (3.3 per cent), Babesia canis vogeli (2.0 per cent), Babesia gibsoni (2.0 per
      cent), Babesia canis canis (1.3 per cent) and Theileria annae (0.7 per cent).
      Coinfections were present in seven of the dogs and they were significantly
      associated with L infantum infection (P=0.024). There was a significant
      correlation between clinical signs of illness and the load of L infantum.

PMID- 19168882
TI  - IS1245 RFLP analysis of strains of Mycobacterium avium subspecies hominissuis
      isolated from pigs with tuberculosis lymphadenitis in Portugal.
AB  - From the end of 2004 increasing numbers of tuberculosis-like lesions were
      detected in regular meat inspections of pigs at regional abattoirs. Mycobacterium
      avium subspecies hominissuis was identified as the cause of this outbreak of
      tuberculosis lymphadenitis by IS901 and IS1245 duplex PCR and FR300 PCR. In order
      to detect the source and route of infection, IS1245 restriction fragment length
      polymorphism (RFLP) analysis was used to type 54 strains (50 from pigs, one from
      a cow, two from wild boar and one from peat) isolated in 12 different regions of
      Portugal. A total of 51 different patterns were obtained with most strains giving
      a high IS1245 copy number (between seven and 27) with a complex RFLP pattern.
      Twenty-three strains were gathered in 11 clusters, defined as having at least 80
      per cent similarity. Identical isolates were obtained from one herd in Lisbon
      (two isolates), one herd in Setubal (two isolates) and in two isolates from
      different herds in the same region. No distinctive geographical clustering was
      found among the 54 strains. These results indicate that strains of M hominissuis
      are very heterogeneous and widespread in pigs in Portugal. No major common source
      of the infection was identified.

PMID- 19168883
TI  - Salmonellosis in cats in the United Kingdom: 1955 to 2007.

PMID- 19168884
TI  - Induction of anaesthesia in wild rabbits using a new alfaxalone formulation.

PMID- 19168885
TI  - Deaths in rockhopper penguins.

PMID- 19168886
TI  - Possible diethylene glycol toxicity in a dog.

PMID- 19168887
TI  - Veterinary nurse training: review of standards.

PMID- 19168888
TI  - Avian influenza virus (H5N1) in chickens in India.

PMID- 19168889
TI  - Being in nature: an innovative framework for incorporating nature in therapy with
      older adults.
AB  - This article describes a creative framework in which nature is incorporated in
      therapy with older adults. Using an example from practice, it illustrates how the
      integration of concepts from the narrative approach and the innovative nature
      therapy framework can help older people expand their perspectives, connect with
      strength, and expand their coping strategies, while gaining a wider sense of
      acceptance and completion in life.

PMID- 19168890
TI  - Physical activity promotion among underserved adolescents: "make it fun, easy,
      and popular".
AB  - There is a paucity of studies regarding noncurricular physical activity promotion
      interventions among adolescents, and even less such research pertaining to
      underserved youth. This article describes the development and implementation of a
      noncurricular, school-based physical activity promotion program designed for a
      multiethnic, underserved population of adolescents. The program's impact on
      leisure-time physical activity (LTPA) and on physical activity enjoyment (PAE) is
      also presented. The 16-week program, named FunAction, utilizes social marketing
      principles. Control (n = 90) and intervention (n = 131) students are assessed pre
      and postintervention for levels of LTPA and PAE. Results indicate that although
      the program did not contribute to an increase in LTPA or PAE among intervention
      group students, participation in the program was elevated. This study offers
      preliminary evidence that noncurricular physical activity promotion programs that
      apply social marketing principles can be effective in engaging multiethnic,
      underserved adolescents in physical activity.

PMID- 19168891
TI  - Mapping a message for faith leaders: encouraging community health promotion with
      local health data.
AB  - This study reports the use of a community-based health survey to share local
      health information with faith leaders. Geographical information systems software
      identified survey respondents within 2 km (1.25 miles) of places of worship.
      Results were tabulated for the community surrounding each place of worship and
      were compared with city- and county-level data. Faith leaders were presented with
      community-specific reports describing the health attributes of residents who
      lived in the surrounding area, in order to assist with the identification issues
      of concern and opportunities to develop health ministries to address these
      issues. Faith leaders were encouraged to share this information with members of
      their faith community and develop means of obtaining additional information on
      the people of interest. We believe that engaging faith leaders with neighborhood
      specific health information will be critical in providing an understanding of the
      importance of their voice in improving health outcomes of their faith community,
      the surrounding neighborhood, and the community at large. Our goal is to empower
      faith leaders to understand personal and community health issues and to act as a
      conduit for health-related information and health promotion at a local level.
      Church health teams developed an HIV and sexually transmitted infection
      prevention program for African American adolescents and young adults.

PMID- 19168892
TI  - Multiple genes on chromosome 7 regulate dopaminergic amacrine cell number in the
      mouse retina.
AB  - PURPOSE: The size of neuronal populations is modulated by gene variants that
      influence cell production and survival, in turn influencing neuronal
      connectivity, function, and disease risk. The size of the dopaminergic amacrine
      (DA) cell population is a highly heritable trait exhibiting sixfold variation
      among inbred strains of mice and is used here to identify genes that modulate the
      number of DA cells. METHODS: The entire population was counted in retinal
      wholemounts from 37 genetically defined lines of mice, including six standard
      inbred strains, 25 recombinant inbred strains (AXB/BXA), reciprocal F1 hybrids, a
      chromosome (Chr) 7 consomic line, and three additional genetically modified
      lines. RESULTS: Much of this variation was mapped to a broad locus on Chr 7
      (Dopaminergic amacrine cell number control, Chr 7 [Dacnc7]). The Dacnc7 locus is
      flanked by two candidate genes known to modulate the number of other types of
      retinal neuron-the proapoptotic gene, Bax, and tyrosinase. The Tyr mutation was
      shown to modulate DA cell number modestly, though in the direction opposite that
      predicted. In contrast, Bax deficiency increased the population fourfold. Bax
      expression was significantly greater in the A/J than in the C57BL/6J strain, an
      effect that may be attributed to an SNP in a p53 consensus binding site known to
      modulate transcription. Finally, we note a strong candidate situated at the peak
      of the Dacnc7 locus, Lrrk1, a Parkinson's disease gene exhibiting missense
      mutations segregating within the AXB/BXA cross. CONCLUSIONS: Multiple polymorphic
      genes on Chr 7 modulate the size of the population of DA cells.

PMID- 19168893
TI  - Quantitative subanalysis of cystoid spaces and outer nuclear layer using optical
      coherence tomography in age-related macular degeneration.
AB  - PURPOSE: To use optical coherence tomography (OCT) to quantify intraretinal
      cystoid spaces (ICSs) and the outer nuclear layer (ONL) in patients with
      neovascular age-related macular degeneration (AMD) and to investigate the
      correlation of these parameters with visual acuity. METHODS: StratusOCT (Carl
      Zeiss Meditec, Inc., Dublin, CA) images were collected from 53 patients receiving
      their initial treatment with intravitreous ranibizumab. Images were analyzed with
      custom software (OCTOR) that allows accurate manual segmentation of OCT B-scans
      and provides thickness/volume measurements of ICS, ONL, neurosensory retina,
      pigment epithelial detachments (PEDs), subretinal fluid (SRF), and subretinal
      tissue (SRT). Univariate and multivariate analyses were used to correlate OCT
      parameters with best corrected Snellen visual acuity. Reproducibility was
      assessed with weighted kappa statistics and intraclass correlation coefficients.
      RESULTS: A multivariate linear regression model with adjusted R(2) showed that
      ONL volume and SRT thickness significantly correlated with Snellen visual acuity
      (R(2) = 0.15, P = 0.002 and R(2) = 0.19, P = 0.001, respectively) with an overall
      model R(2) of 0.34. Adjustment of ONL volume for ICS did not improve correlation
      with visual acuity, and ICS volume did not independently correlate with visual
      acuity. Weighted kappa statistics showed excellent intergrader agreement for both
      ICS and ONL measurements. CONCLUSIONS: The results suggest that an increased
      total volume of the ONL is associated with decreased visual acuity in neovascular
      AMD and that the total volume of ICS does not correlate with visual acuity.
      Although the correlations detected in this study are modest, quantitative
      subanalysis of OCT images may be of greater clinical relevance in the context of
      more advanced OCT technology.

PMID- 19168894
TI  - Elevation of human alpha-defensins and S100 calcium-binding proteins A8 and A9 in
      tear fluid of patients with pterygium.
AB  - PURPOSE: The pathogenesis of pterygia is still not well understood. Recent
      studies suggest that it may be associated with inflammation and progressive
      proliferation triggered by ultraviolet radiation. In this study the authors
      determined that the inflammatory nature of pterygium is reflected in the protein
      components of tears. METHODS: Consent for this study was obtained from 12
      patients (average age, 57 years; eight men, four women) with unilateral
      pterygium. Tears were collected from diseased eyes and contralateral healthy
      control eyes with the use of fire-polished 10-microL calibrated glass pipettes
      before pterygium surgery. Tear protein profiles obtained from diseased and
      control eyes (seven patient samples) were compared using surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology.
      Tears from another five patients with pterygium were used for subsequent protein
      identification experiments with nano-LC coupled with nano-electrospray tandem
      mass spectrometry (nano-ESI-MS/MS). RESULTS: SELDI mass spectra showed that one
      peptide cluster with a molecular weight of 3.4 kDa and two proteins with
      molecular weights of 10.8 kDa and 12.7 kDa were elevated in tears of eyes with
      pterygium. Proteins of interest were identified by nano-LC-ESI-MS/MS as human
      alpha-defensins (human neutrophil peptide [HNP]-1, HNP-2, HNP-3) and S100 calcium
      binding proteins A8 and A9. Mean concentrations (n = 7) of alpha-defensins were
      1.33 +/- 0.47 microg/mL (HNP-1, P < 0.015) and 0.61 +/- 0.23 microg/mL (HNP-2, P
      < 0.012) for pterygium eyes and 0.17 +/- 0.12 microg/mL (HNP-1) and 0.02 +/- 0.02
      microg/mL (HNP-2) for fellow control eyes. Compared with tears from eyes without
      pterygium or other abnormalities, the level of S100 A8 increased 1.4- to 13.4
      fold (average fold change, 4.5) and S100 A9 increased 1.5- to 4.0-fold (average
      fold change, 2.3) in 4 of 7 patients. CONCLUSIONS: The upregulated expression of
      human alpha-defensins and S100 A8 and A9 in tear fluids of patients with
      pterygium indicates that they may be part of the response of the ocular surface
      to the formation of this fibrovascular tissue or the accompanying inflammation.
      They may also serve as a useful indicator for predicting recurrent pterygium.

PMID- 19168895
TI  - Trichostatin a inhibits corneal haze in vitro and in vivo.
AB  - PURPOSE: Trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to
      suppress TGF-beta-induced fibrogenesis in many nonocular tissues. The authors
      evaluated TSA cytotoxicity and its antifibrogenic activity on TGF-beta-driven
      fibrosis in the cornea with the use of in vitro and in vivo models. METHODS:
      Human corneal fibroblasts (HSFs) were used for in vitro studies, and New Zealand
      White rabbits were used for in vivo studies. Haze in the rabbit cornea was
      produced with photorefractive keratectomy (PRK) using excimer laser. Trypan blue
      exclusion and MTT assays evaluated TSA cytotoxicity to the cornea. Density of
      haze in the rabbit eye was graded with slit lamp biomicroscopy. Real-time PCR,
      immunoblotting, or immunocytochemistry was used to measure alpha-smooth muscle
      actin (SMA), fibronectin, and collagen type IV mRNA or protein levels. TUNEL
      assay was used to detect cell death. RESULTS: TSA concentrations of 250 nM or
      less were noncytotoxic and did not alter normal HSF morphology or proliferation.
      TGF-beta1 treatment of HSF significantly increased mRNA and protein levels of SMA
      (9-fold), fibronectin (2.5-fold), and collagen type IV (2-fold). TSA treatment
      showed 60% to 75% decreases in TGF-beta1-induced SMA and fibronectin mRNA levels
      and 1.5- to 3.0-fold decreases in protein levels but had no effect on collagen
      type IV mRNA or protein levels in vitro. Two-minute topical treatment of TSA on
      rabbit corneas subjected to -9 D PRK significantly decreased corneal haze in
      vivo. CONCLUSIONS: TSA inhibits TGF-beta1-induced accumulation of extracellular
      matrix and myofibroblast formation in the human cornea in vitro and markedly
      decreases haze in rabbit cornea in vivo.

PMID- 19168896
TI  - Multiple endpoint analysis of the 3D-reconstituted corneal epithelium after
      treatment with benzalkonium chloride: early detection of toxic damage.
AB  - PURPOSE: To investigate the effects of benzalkonium chloride (BAK) on the human
      reconstituted corneal epithelial model (HCE) and to optimize the operating
      potential of this model in the field of ophthalmic toxicology. METHODS: The HCEs
      were treated with 0.001% to 0.5% BAK for 24 hours followed or not by a 24-hour
      postincubation period. To complete the histologic analysis, the authors designed
      a new MTT procedure to assess cellular viability. Frozen sections were analyzed
      by using fluorescence confocal microscopy for the presence of TUNEL, activated
      caspase-3, Ki67, ICAM-1, HLA-DR, E-cadherin, and occludin. Occludin gene
      expression was also investigated by using quantitative RT-PCR. RESULTS: The MTT
      test revealed a dose-dependent response of BAK with significant toxic effects for
      concentrations as low as 0.005%. Increasing BAK concentrations induced an
      increased number of apoptotic cells, found from the superficial to the deeper
      layers, with the activation of caspase-3 at 0.01% and 0.02% concentrations. The
      number of Ki67- and ICAM-1-positive cells increased with 0.01% BAK and with
      0.001% to 0.01% BAK, respectively. BAK induced the dose-dependent disappearance
      of occludin in the superficial layers while increasing its gene expression up to
      the 0.02% BAK concentration. CONCLUSIONS: Fluorescence techniques conjugated with
      confocal microscopy on 3D-reconstructed corneal epithelia were well suited for
      the investigation of toxicological markers such as cell junction alteration,
      apoptosis, cell activation, and proliferation and gave relevant results compared
      with the known human data. They complement the new sensitive MTT test and improve
      the operating potential of this new, valuable 3D model in ophthalmic toxicology.

PMID- 19168897
TI  - Intraocular pressure and calculated diastolic ocular perfusion pressure during
      three simulated steps of phacoemulsification in vivo.
AB  - PURPOSE: To investigate the fluctuations of directly measured intraocular
      pressure (IOP) and induced diastolic ocular perfusion pressure (DOPP) during
      three simulated steps of phacoemulsification in vivo. METHODS: Twenty-five eyes
      of 25 patients who underwent phacoemulsification were evaluated. A pressure
      transducer was inserted into the anterior chamber to measure IOP directly. The
      cortical cleanup and viscoelastic removal, nuclear disassembly, and anterior
      capsular polishing stages of phacoemulsification were simulated. Baseline,
      static, and dynamic IOP measurements at each stage were conducted before a
      routine phacoemulsification procedure was performed. DOPP was determined as the
      difference between diastolic blood pressure and IOP. RESULTS: The directly
      measured IOP fluctuated from 13 +/- 4.7 to 96 +/- 6.2 mm Hg during the simulated
      steps of phacoemulsification (repeated-measurement ANOVA, P < 0.001). It was
      elevated more than 39 mm Hg compared with the baseline in static and dynamic
      measurements (post hoc, P < 0.001). Static DOPPs were lower than 0 mm Hg in all
      cases during simulated cortical cleanup and viscoelastic removal and in 19 cases
      during simulated nuclear disassembly. Dynamic DOPPs were lower than 0 mm Hg in 14
      cases during simulated cortical cleanup and viscoelastic removal. CONCLUSIONS:
      IOP and DOPP fluctuate widely during simulated steps of phacoemulsification.
      Further studies may be needed to establish the effect of the transient
      fluctuations in DOPP on visual function.

PMID- 19168898
TI  - Liposome assay for evaluating ocular toxicity of surfactants.
AB  - PURPOSE: The ocular toxicity of various compounds is typically determined by the
      Draize eye test, which has been criticized in the past for its lack of
      reproducibility and the cruelty associated with harsh testing conditions for
      animals. In this study, a liposome-based assay was developed for estimating
      ocular toxicity of surfactants. METHODS: The release of calcein dye from
      liposomes induced by interactions with surfactants was studied and correlated to
      Draize eye scores. First, the liposome assay was conducted for various
      surfactants at identical concentrations and correlated to the Draize scores.
      Next, mechanistic and geometric considerations were used to determine the
      appropriate surfactant concentration that should be used in the liposome assay.
      RESULTS: Correlations between the percentage of dye released and the Draize
      scores were drastically improved after surfactant concentrations were chosen
      based on CMC/200, where CMC is the critical micelle concentration of the
      surfactants. With this choice of surfactant concentration, excellent correlations
      were obtained with Draize scores from three separate sources and two different
      ocular surfactant loadings (Pearson = 0.99, 0.82, 0.78, and 0.74; Spearman =
      0.94, 0.79, 0.79, and 0.85). Subsequently, the ocular toxicities of six nonionic
      surfactants, Brij 700, -58, -56, -78, -97, and -98 were shown to be minimal based
      on the proposed correlations. CONCLUSIONS: The modified liposome assay developed
      in this study could be used in conjunction with other in vitro assays to obtain
      initial estimates for ocular toxicities and thus minimize the need for the Draize
      test.

PMID- 19168899
TI  - Identification of optical density ratios in subretinal fluid as a clinically
      relevant biomarker in exudative macular disease.
AB  - PURPOSE: To investigate the potential role of optical density ratios (ODRs)
      obtained from subretinal fluid analysis in exudative macular disease and to
      identify the predictive role of ODRs under therapy in comparison to conventional
      morphometric measurements (CMMs). METHODS: Fifteen patients with neovascular age
      related macular degeneration (nAMD) and 15 with acute central serous
      chorioretinopathy (CSC) were included in this prospective comparative and
      interventional case series. High-definition optical coherence tomography (SD-OCT)
      was performed according to a standardized protocol. nAMD patients received a
      standard treatment consisting of three monthly doses of intravitreous
      ranibizumab. Best corrected visual acuity (BCVA) was assessed at baseline (BSL)
      and weeks 2, 4, and 12. SD-OCT parameters were compared between CSC and nAMD at
      baseline. Predictive factors for functional recovery under ranibizumab treatment
      were identified in patients with nAMD. RESULTS: ODR showed highly significant
      differences between CSC and nAMD, whereas it was not possible to differentiate
      between these diseases on the basis of CMM. During follow-up, CMM correlated with
      BCVA at BSL only, whereas ODR showed a significant correlation with BCVA at week
      4 and 12 during antiangiogenic therapy. CONCLUSIONS: Results suggest that CMM may
      correlate with BCVA at BSL, but has limited predictive value regarding recovery
      of visual function. Most interesting, ODR correlated with BCVA under therapy and
      was the only parameter that was pathognomic for nAMD in contrast to CSC in this
      study. ODR may reflect the status of the blood-retina barrier and may be used for
      pathophysiologic differentiation and prognostic purposes in exudative macular
      disease.

PMID- 19168900
TI  - Expression and modulation of RPE cell membrane complement regulatory proteins.
AB  - PURPOSE: Complement, inflammation, and oxidant injury contribute to age-related
      macular degeneration (AMD). Membrane complement regulatory proteins (mCRPs) such
      as CD46, CD55, and CD59, protect host cells from complement attack. The factors
      that regulate RPE mCRP expression are not well understood. In this study, the
      authors sought to determine whether cytokines and hydroquinone (HQ) affect mCRP
      expression in cultured human RPE (hRPE) and cultured mouse RPE (mRPE) cells.
      METHODS: Cultured hRPE and mRPE cells were stimulated with cytokines for various
      times or with HQ for multiple 6-hour periods. mRNA and protein expression of
      mCRPs in cultured hRPE cells from 10 donors, native hRPE, and mouse eyecups and
      native mRPE cells were evaluated by real-time RT-PCR, Western blot analysis, and
      flow cytometry, respectively. RESULTS: Three mCRPs were expressed in cultured
      hRPE cells (CD59>CD46>CD55). CD46 and CD59 protein were detected in native hRPE
      cells. CD59 protein levels in cultured hRPE cells were higher than in native hRPE
      cells. CD46 protein polymorphisms were observed in cultured hRPE cells. Cultured
      hRPE cell mCRP expression was upregulated by TNF-alpha, IL-1beta, and a
      repetitive nonlethal dose of HQ. CD59a levels were higher in mouse eyecups than
      in nonocular tissues. Mouse mCRP mRNA and protein were detected in native mRPE
      cells. Responsiveness to cytokines in cultured mRPE cells differed from that in
      cultured hRPE cells. CONCLUSIONS: Human and mouse RPE cell mCRPs are upregulated
      by inflammatory cytokines and repetitive nonlethal oxidant exposure in a species
      specific manner. Increased cell mCRPs may help to protect RPE cells from
      complement- and oxidant-mediated injury in diseases such as AMD.

PMID- 19168901
TI  - Functional and structural changes resulting from strain differences in the rat
      model of oxygen-induced retinopathy.
AB  - PURPOSE: Results of studies that compared the racial incidence of retinopathy of
      prematurity (ROP) suggested that ocular pigmentation might offer protection
      against the development of severe ROP. The structural and functional consequences
      of postnatal hyperoxia (oxygen-induced retinopathy; OIR) were compared in albino
      Sprague-Dawley (SD) and pigmented Long-Evans (LE) rats to verify this finding.
      METHODS: Newborn rats were exposed to 80% O(2) during selected postnatal day
      intervals. The severity of the OIR was determined by examining retinal flatmounts
      (retinal vasculature assessment), protein level quantification and cellular
      localization of fibroblast growth factor (FGF)-2 and ciliary neurotrophic factor
      (CNTF; Western blot analysis and immunohistochemistry, respectively), retinal
      histology, and photopic and scotopic electroretinograms (ERGs). RESULTS:
      Irrespective of the parameter considered, structural and functional deficits
      resulting from postnatal hyperoxia were significantly more pronounced in LE rats.
      Although FGF-2 levels in LE rats had a tendency to increase after hyperoxia
      compared with normoxic littermates, it did not reach statistical significance. A
      similar finding was observed in SD rats. Of interest, however, baseline levels of
      FGF-2 were approximately four to five times higher in SD rats than in LE rats.
      There was a similar, hyperoxia-induced increase in CNTF levels between SD and LE
      rats. CONCLUSIONS: The findings suggest an increased susceptibility of newborn LE
      rats to postnatal hyperoxia in comparison with SD rats. Whether a pro-oxidant
      rather than antioxidant role of melanin or other genetic factors can explain
      these differences in oxygen susceptibility of the animal model of this
      retinopathy, remains to be determined.

PMID- 19168902
TI  - The role of a glycoprotein K (gK) CD8+ T-cell epitope of herpes simplex virus on
      virus replication and pathogenicity.
AB  - PURPOSE: The authors recently reported that a recombinant HSV-1 expressing two
      extra copies of glycoprotein K (gK) exacerbated corneal scarring (CS) in mice.
      The authors also identified a peptide, STVVLITAYGLVLVW, within the signal
      sequence of gK as an immunodominant gK T-cell-stimulatory region both in vitro
      and in vivo and identified a highly conserved potential CD8(+) T-cell epitope
      (ITAYGLVL) within the peptide. In this study, the effect of giving this octamer
      (8mer) as an eye drop 1 hour before ocular infection with HSV-1 was investigated.
      METHODS: Naive mice and rabbits received the gK 8mer or control peptides as eye
      drops and were then ocularly infected with HSV-1. Virus replication in the eye
      and trigeminal ganglia (TG), survival, CS, and relative amounts of gB, gK, CD4,
      CD8, IFN-gamma, and granzyme A/B transcripts were determined in the cornea and TG
      of infected animals at various times after infection. The effect of the gK 8mer
      was also analyzed in immunized HLA transgenic mice. RESULTS: The gK 8mer resulted
      in a short-term significant increase in virus replication in the eyes of BALB/c
      mice, C57BL/6 mice, and NZW rabbits. gK 8mer treatment also increased viral
      neurovirulence and viral induced CS in ocularly infected mice. Moreover, in HSV
      infected humanized HLA-A*0201 transgenic mice, the gK 8mer epitope induced strong
      IFN-gamma-producing cytotoxic CD8(+) T-cell responses, as assessed by CD107a/b
      expression and IFN-gamma ELISAs. CONCLUSIONS: gK 8mer induced CD8(+) T-cell
      responses were unlikely to occur soon enough to account for increased virus
      replication on day 1 after infection. In contrast, the data are consistent with
      CD8(+) T cells being involved in the appearance of CS at late times after
      infection. In addition, the gK peptide may affect viral replication and innate
      immune responses through other undefined mechanisms.

PMID- 19168903
TI  - Depression of intraocular pressure following inactivation of connexin43 in the
      nonpigmented epithelium of the ciliary body.
AB  - PURPOSE: Conditional inactivation of connexin43 (Cx43) in the pigmented
      epithelium of the mouse eye results in a reduction in aqueous humor production
      and complete loss of the vitreous chamber. It was proposed that gap junctions
      between pigmented and nonpigmented epithelia of the ciliary body are critical for
      the production of the aqueous humor. To form such junctions, Cx43 in the
      pigmented epithelium must interact with connexin(s) present in the adjacent cells
      of the nonpigmented epithelium. The importance of Cx43 expression in the
      nonpigmented epithelium for the establishment of gap junctions and the regulation
      of intraocular pressure was tested. METHODS: To inactivate Cx43 in the
      nonpigmented epithelium of the mouse eye, a mouse line was crossed with a floxed
      Cx43 locus (Cx43(flox/flox)) and a transgenic mouse line expressing cre
      recombinase under the control of the Pax6alpha promoter. General eye structure
      was evaluated by light microscopy, gap junctions were analyzed by electron
      microscopy, and intraocular pressure was directly assessed with micropipettes.
      RESULTS: In Pax6alpha-cre/Cx43(flox/flox) mice, Cx43 was partially inactivated in
      the nonpigmented epithelium of the ciliary body and iris. Animals developed
      dilatations between the pigmented and nonpigmented epithelia and displayed a
      significant reduction in intraocular pressure. However, gap junctions between the
      ciliary epithelial layers were decreased but not eliminated. CONCLUSIONS: Cx43
      expression in the nonpigmented epithelium of the ciliary body contributes to the
      formation of gap junctions with the cells of the pigmented epithelium. These gap
      junctions play a critical role in maintaining the physical integrity of the
      ciliary body epithelium. Although the partial loss of Cx43 from the nonpigmented
      epithelium was correlated with a measurable drop in intraocular pressure,
      possible changes in Cx43 in the aqueous outflow pathway may provide an additional
      contribution to the observed phenotype.

PMID- 19168904
TI  - SPARC-null mice exhibit lower intraocular pressures.
AB  - PURPOSE: SPARC is a matricellular protein that is highly expressed in remodeling
      tissues, including the trabecular meshwork and ciliary body. The hypothesis for
      the study was that SPARC contributes to the regulation of intraocular pressure
      (IOP). The IOPs of SPARC-null mice, their corresponding wild-type (WT), and
      heterozygous animals were compared. METHODS: Diurnal and nocturnal IOPs of
      C57Bl/6x129SvJ WT, SPARC-null, and heterozygous mice were measured.
      Fluorophotometric measurements were made to assess aqueous turnover. Central
      corneal thickness (CCT) was measured using histology, ultrasound biomicroscopy,
      and optical coherence tomography. Iridocorneal angles were examined using light
      microscopy (LM). RESULTS: During the day, the mean IOP of SPARC-null mice (n =
      142, 16.9 +/- 2.4 mm Hg) was lower than that of both WT mice (n = 104, 19.9 +/-
      2.9 mm Hg; P < 10(-12)), and heterozygotes (n = 38, 19.3 +/- 2.5 mm Hg; P < 10(
      4)). At night, SPARC-null mice also exhibited a blunted increase in IOP in
      comparison to WT and heterozygous mice. CCTs were not significantly different
      between WT and SPARC-null mice. Heterozygous mice tended to have thicker corneas
      (3.4%). Fluorophotometric measurements suggest that aqueous turnover rates in
      SPARC-null mice are equal to if not greater than rates in WT mice. LM of the
      SPARC-null iridocorneal angle revealed morphology that is indistinguishable from
      WT. CONCLUSIONS: SPARC-null mice have lower IOPs than do their WT counterparts
      with equal CCTs. The rate of aqueous turnover suggests that the mechanism is
      enhanced outflow resistance.

PMID- 19168905
TI  - Heterogeneous distribution of axonal cytoskeleton proteins in the human optic
      nerve.
AB  - PURPOSE: Cytoskeleton proteins play a critical role in maintaining retinal
      ganglion cell structure, viability, and function. This study documents the
      distribution of cytoskeleton protein subunits in the various regions of the
      normal human optic nerve and identifies important relationships among
      mitochondria, myelin, and neurofilament proteins. METHODS: Twenty-three optic
      nerves from human cadavers were used. Confocal microscopy was used to examine the
      distribution of neurofilament light, neurofilament medium, neurofilament heavy
      (phosphorylated and unphosphorylated), neurofilament heavy (phosphorylated only),
      actin, and microtubule associated protein (MAP)-1 along the sagittal plane of the
      optic nerve. Comparisons were made among superior, middle, and inferior regions
      and also among temporal, central, and nasal portions of the optic nerve.
      Colocalization of neurofilament light, mitochondrial cytochrome c oxidase (COX),
      and myelin was also performed. RESULTS: There are significant differences in the
      pattern and distribution of neurofilament protein subunits, actin, and MAP-1
      along the sagittal plane of the optic nerve. Cytoskeleton proteins and COX
      mitochondria are found in highest concentrations in the prelaminar and lamina
      cribrosa regions. COX and neurofilament light occurs predominantly in
      unmyelinated nerve, with a significant decrease in concentration occurring on
      optic nerve myelination. CONCLUSIONS: The heterogeneous distribution of
      cytoskeleton proteins along the sagittal plane may be an important functional
      adaptation that reflects the nonuniform nature of the physiological and
      structural environment of the optic nerve. The heterogeneous distribution of
      cytoskeleton proteins may also partly account for the asymmetric pattern of optic
      nerve damage after intraocular pressure elevation.

PMID- 19168906
TI  - Interactions between geometry and mechanical properties on the optic nerve head.
AB  - PURPOSE: To determine the relative strength, independently and in interaction, of
      the influence of factors representing the geometry and mechanical properties on
      the IOP-induced stresses and strains within the optic nerve head (ONH). METHODS:
      A computational model of the eye was developed such that 21 factors could be
      varied independently or simultaneously. A fractional factorial screening analysis
      was used to identify the factors and interactions with the largest influences on
      the lamina cribrosa (LC) and prelaminar neural tissue (PLNT). RESULTS: Nine
      factors and their interactions accounted for the majority of the variance in the
      responses (between 95% and 99.8%). These factors were: the properties of the
      sclera (modulus, eye radius, and shell thickness), LC (modulus and radius), PLNT
      (modulus and compressibility), and optic nerve (modulus), and IOP. The
      interactions were stronger on the PLNT than on the LC (up to 16.4% and 9.0% of
      the response variances, respectively). No factor was the most influential on all
      the responses or sufficient to ensure high or low levels of strain or stress.
      Although the modulus of the sclera was among the most influential factors, its
      effects could be outweighed by other factors. CONCLUSIONS: There were strong
      interactions between and within the geometry and mechanical properties of the
      tissues of the ONH. This suggests that to ascertain individual susceptibility to
      IOP it may be necessary to determine several properties of the eye, as well as
      their interactions. The influential factors and their covariances should be
      better characterized.

PMID- 19168907
TI  - Comparing ultrasound biometry with partial coherence interferometry for
      intraocular lens power calculations: a randomized study.
AB  - PURPOSE: To determine whether intraocular lens (IOL) power calculations for
      cataract surgery as measured by postoperative refractive error using partial
      coherence interferometry (PCI) are more accurate in improving postoperative
      outcomes than applanation ultrasound biometry (AUS). METHODS: A double-blind
      randomized controlled trial consisting of 205 patients was undertaken by the
      Southern Health Ophthalmology Unit, Victoria, Australia. Mean absolute
      postoperative refractive error (MAE) represented the dependent variable; the
      biometric technique (PCI; AUS) used to determine the IOL power to be implanted in
      the surgical eye represented the independent variable. An intention-to-treat
      analysis was used to prevent loss of randomization caused by the effects of
      crossover and drop-out. RESULTS: The MAE in patients with implanted PCI
      calculated IOLs was 0.40 +/- 0.37 D (SD; 95% confidence interval [CI], 0.32-0.48
      D) compared with 0.45 +/- 0.41 D (SD; 95% CI, 0.36-0.54 D) for patients with
      implanted AUS-calculated IOLs. There was no statistically significant difference
      between MAE in patients with implanted PCI-calculated IOLs and that in patients
      with AUS-calculated IOLs in analysis of best possible outcomes (t(167) = 1.0, P =
      0.315). CONCLUSIONS: The results of this trial demonstrated that the calculation
      of IOL power based on ocular axial length measurement with PCI technology
      provided no clinical advantage over conventional applanation ultrasound, as
      measured by postoperative refractive outcome (anzctr.org.au number,
      ACTRN12608000077369).

PMID- 19168908
TI  - Thyroid involvement in disseminated zygomycosis by Cunninghamella bertholletiae:
      2 cases and literature review.
AB  - Thyroid involvement is very rare in disseminated zygomycosis. We describe two
      cases of thyroiditis due to Cunninghamella bertholletiae diagnosed though a
      necropsy study and the only five previous cases of thyroid zygomycosis reported
      in the literature are revised.

PMID- 19168909
TI  - RNAither, an automated pipeline for the statistical analysis of high-throughput
      RNAi screens.
AB  - SUMMARY: We present RNAither, a package for the free statistical environment R
      which performs an analysis of high-throughput RNA interference (RNAi) knock-down
      experiments, generating lists of relevant genes and pathways out of raw
      experimental data. The library provides a quality assessment of the signal
      intensities, as well as a broad range of options for data normalization,
      different statistical tests for the identification of significant siRNAs, and a
      significance analysis of the biological processes involving corresponding genes.
      The results of the analysis are presented as a set of HTML pages. Additionally,
      all values and plots are available as either text files or pdf and png files.
      AVAILABILITY: http://bioconductor.org/

PMID- 19168910
TI  - MOTIFATOR: detection and characterization of regulatory motifs using prokaryote
      transcriptome data.
AB  - SUMMARY: Unraveling regulatory mechanisms (e.g. identification of motifs in cis
      regulatory regions) remains a major challenge in the analysis of transcriptome
      experiments. Existing applications identify putative motifs from gene lists
      obtained at rather arbitrary cutoff and require additional manual processing
      steps. Our standalone application MOTIFATOR identifies the most optimal
      parameters for motif discovery and creates an interactive visualization of the
      results. Discovered putative motifs are functionally characterized, thereby
      providing valuable insight in the biological processes that could be controlled
      by the motif. AVAILABILITY: MOTIFATOR is freely available at
      http://www.motifator.nl.

PMID- 19168911
TI  - Sparse linear discriminant analysis for simultaneous testing for the significance
      of a gene set/pathway and gene selection.
AB  - MOTIVATION: Pathway and gene set-based approaches for the analysis of gene
      expression profiling experiments have become increasingly popular for addressing
      problems associated with individual gene analysis. Since most genes are not
      differently expressed, existing gene set tests, which consider all the genes
      within a gene set, are subject to considerable noise and power loss, a concern
      exacerbated in studies in which the degree of differential expression is moderate
      for truly differentially expressed genes. For a significantly differentially
      expressed pathway, it is also of substantial interest to select important genes
      that drive the differential expression of the pathway. METHODS: We develop a
      unified framework to jointly test the significance of a pathway and to select a
      subset of genes that drive the significant pathway effect. To achieve dimension
      reduction and gene selection, we decompose each gene pathway into a single score
      by using a regularized form of linear discriminant analysis, called sparse linear
      discriminant analysis (sLDA). Testing for the significance of the pathway effect
      proceeds via permutation of the sLDA score. The sLDA-based test is compared with
      competing approaches with simulations and two applications: a study on the effect
      of metal fume exposure on immune response and a study of gene expression profiles
      among Type II Diabetes patients. RESULTS: Our results show that sLDA-based
      testing provides a powerful approach to test for the significance of a
      differentially expressed pathway and gene selection. AVAILABILITY: An
      implementation of the proposed sLDA-based pathway test in the R statistical
      computing environment is available at http://www.hsph.harvard.edu/~mwu/software/.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 19168912
TI  - Variable locus length in the human genome leads to ascertainment bias in
      functional inference for non-coding elements.
AB  - MOTIVATION: Several functional gene annotation databases have been developed in
      the recent years, and are widely used to infer the biological function of gene
      sets, by scrutinizing the attributes that appear over- and underrepresented.
      However, this strategy is not directly applicable to the study of non-coding DNA,
      as the non-coding sequence span varies greatly among different gene loci in the
      human genome and longer loci have a higher likelihood of being selected purely by
      chance. Therefore, conclusions involving the function of non-coding elements that
      are drawn based on the annotation of neighboring genes are often biased. We
      assessed the systematic bias in several particular Gene Ontology (GO) categories
      using the standard hypergeometric test, by randomly sampling non-coding elements
      from the human genome and inferring their function based on the functional
      annotation of the closest genes. While no category is expected to occur
      significantly over- or underrepresented for a random selection of elements,
      categories such as 'cell adhesion', 'nervous system development' and
      'transcription factor activities' appeared to be systematically overrepresented,
      while others such as 'olfactory receptor activity'-underrepresented. RESULTS: Our
      results suggest that functional inference for non-coding elements using gene
      annotation databases requires a special correction. We introduce a set of
      correction coefficients for the probabilities of the GO categories that accounts
      for the variability in the length of the non-coding DNA across different loci and
      effectively eliminates the ascertainment bias from the functional
      characterization of non-coding elements. Our approach can be easily generalized
      to any other gene annotation database.

PMID- 19168913
TI  - AssociationViewer: a scalable and integrated software tool for visualization of
      large-scale variation data in genomic context.
AB  - SUMMARY: We present a tool designed for visualization of large-scale genetic and
      genomic data exemplified by results from genome-wide association studies. This
      software provides an integrated framework to facilitate the interpretation of SNP
      association studies in genomic context. Gene annotations can be retrieved from
      Ensembl, linkage disequilibrium data downloaded from HapMap and custom data
      imported in BED or WIG format. AssociationViewer integrates functionalities that
      enable the aggregation or intersection of data tracks. It implements an efficient
      cache system and allows the display of several, very large-scale genomic
      datasets. AVAILABILITY: The Java code for AssociationViewer is distributed under
      the GNU General Public Licence and has been tested on Microsoft Windows XP,
      MacOSX and GNU/Linux operating systems. It is available from the SourceForge
      repository. This also includes Java webstart, documentation and example
      datafiles.

PMID- 19168914
TI  - Exercise provocation test for growth hormone secretion: methodologic
      considerations.
AB  - The diagnosis of Growth Hormone (GH) deficiency in children with short stature is
      complex, and in certain cases, might be very difficult. Most of the provocative
      tests used to evaluate GH deficiency use pharmacological agents. The artificial
      nature of the pharmacological tests and the possibility that these tests might
      not always reflect GH secretion under normal physiological conditions provides
      the impetus for a more physiologic test. Exercise is one of the important GH
      releasing physiological stimuli. This review will summarize the current knowledge
      on the methods for performing laboratory exercise provocation test for GH
      secretion in children. In addition to recommendations of more standardized
      exercise protocols and environmental considerations, we will also focus on GH
      responses to exercise in unique populations such as obese children.

PMID- 19168915
TI  - The contribution of stretch-shortening cycle and arm-swing to vertical jumping
      performance in children, adolescents, and adult basketball players.
AB  - This study examined from childhood to adulthood: (1) the effects of
      countermovement (use of stretch-shortening cycle-SSC) and arm-swing (AS) on
      vertical jumping (VJ) performance and (2) the ability to use the SSC and AS
      during VJ. Male basketball players (n = 106) were divided according to their age
      into: children (12.0 +/- 0.23), young adolescents (14.5 +/- 0.41), old
      adolescents (16.9 +/- 0.27), and adults (21.9 +/- 0.32). Each participant
      executed three maximal squat jumps (SJ), countermovement jumps without arms (CMJ)
      and with arms (CMJA). The contribution of SSC and AS was calculated by the
      augmentation (difference and percent change) in performance between CMJ and SJ,
      and CMJA and CMJ, respectively. CMJA performance was significantly (p < .05)
      higher than CMJ and SJ, and CMJ was higher than SJ within all age-groups. There
      were no significant differences (p > .05) among children, young and old
      adolescents, and adults in the percent contribution of SSC and AS to VJ
      performance. The variability in the contribution of SSC and AS to VJ performance
      was about twofold higher in children vs. adults. It appears that the ability to
      use the SSC and AS is not affected by the maturation process in males, trained in
      basketball.

PMID- 19168916
TI  - Aerobic exercise program reduces anger expression among overweight children.
AB  - This study tested the effect of a structured aerobic exercise program on anger
      expression in healthy overweight children. Overweight sedentary children were
      randomly assigned to an aerobic exercise program or a no-exercise control
      condition. All children completed the Pediatric Anger Expression Scale at
      baseline and posttest. Anger Out and Anger Expression scores were lower for the
      exercise condition at posttest. Fitness improvements contributed significantly to
      final models, and points earned for adherence correlated negatively with posttest
      Anger Out. An aerobic exercise program might be an effective strategy to reduce
      anger expression, including reduction of aggressive behavior, in overweight
      children.

PMID- 19168917
TI  - Lung function increases with increasing level of physical activity in school
      children.
AB  - Little is known about the association between physical activity and lung function
      in childhood. We conducted a survey including parental reports of the child's
      participation in physical activity and measurements of lung function. The
      associations between physical activity and lung function were estimated by linear
      regression analysis adjusting for potential confounders in 2,537 children (9 to
      10 years). Using the linear model in exploring the effect of physical activity on
      lung function with those who were physical active less than once a week as the
      reference category, showed that forced expiratory volume in 1 s (FEV1) was
      highest among those who were physical active > or = 4 times a week also when
      adjusting for potential confounders (p = .02). FEV1 increased with 70 ml. A
      similar pattern was present for forced vital capacity (FVC; p = .002). The
      present study suggested that lung function was highest in highly physical active
      children age 9 to 10 years. The implications are that exercise may influence lung
      function, but these findings need to be confirmed using a longitudinal study
      design.

PMID- 19168918
TI  - Impact of curriculum-based bone loading and nutrition education program on bone
      accrual in children.
AB  - The purpose of this study was to investigate the influence of jumping activities
      and nutrition education on bone accretion in prepubescents. Fourth-grade children
      were divided into four groups: jumping (n = 61), nutrition (n = 9), jumping plus
      nutrition (n = 14), and control (n = 28). Interventions spanned the fourth and
      fifth grade academic years. Assessments were gathered at 0, 8 and 20 months.
      Baseline BMD values were (mean +/- SD): lumbar (0.752 +/- 0.095 g/cm2), neck
      (0.794 +/- 0.089 g/cm2) and total (0.907 +/- 0.060 g/cm2). There was a
      significant increase in BMD over time. However, the interventions produced no
      significant effects. Twice weekly jumping and/or biweekly nutrition education did
      not influence bone accrual.

PMID- 19168919
TI  - Skin microvascular reactivity in children and adolescents with type 1 diabetes in
      relation to levels of physical activity and aerobic fitness.
AB  - No studies to date have evaluated the relationship between exercise and
      microvascular function in youth with type 1 diabetes mellitus (T1DM). Twenty-nine
      complication free children and adolescents with T1DM were assessed for skin
      microvascular reactivity, aerobic fitness (VO2peak) and physical activity.
      VO2peak but not physical activity was significantly and independently associated
      with maximal hyperemia of the skin microcirculation (p < .01). No significant
      associations were found between venoarteriolar reflex (VAR) vasoconstriction and
      VO2peak or physical activity. Aerobic fitness may be an important indicator or
      mediator of effective microvascular endothelial function in youth with T1DM.

PMID- 19168920
TI  - The System for Observing Fitness Instruction Time (SOFIT) as a measure of energy
      expenditure during classroom-based physical activity.
AB  - The aim of this investigation was to develop an equation to estimate physical
      activity energy expenditure (PAEE) during a 10-min physically active academic
      lesson using The System for Observing Fitness Instruction Time (SOFIT) and
      demographic information. PAEE (portable indirect calorimeter) and physical
      activity (SOFIT) were simultaneously assessed in 38, 2nd through 5th grade
      children. PAEE and SOFIT were 3.04 +/- 1.1 (kcal/min) and 3.8 +/- 0.4 (score),
      respectively. PAEE was predicted from SOFIT score and body weight [PAEE
      (kcal/min) = (1.384*SOFIT + 0.084*weight (kg)--5.126), R = .81, SEE = 1.23
      kcal/min]. PAEE measured by indirect calorimeter and predicted from SOFIT and
      body weight were 3.04 +/- 1.1 (kcal/min) and 3.04 +/- 0.9 kcal/min) respectively.
      SOFIT and body weight may provide a useful measure of PAEE associated with
      classroom based physical activity.

PMID- 19168921
TI  - Critical hours: physical activity and sedentary behavior of adolescents after
      school.
AB  - The present study examined physical activity and sedentary behavior patterns of
      adolescents between 15.30h and 18.30h. The sample for this study is 1,484 (boys:
      n = 561; girls: n = 923). Boys and girls reported 21 and 19 min of physical
      activity and 24 and 26 min of homework respectively during this period.
      Technology-based sedentary behavior (TV viewing, computer and video game use) was
      significantly higher in boys than girls (boys = 50 mins; girls = 35 mins; p <
      .05). The most prevalent behaviors after school are technology-based sedentary
      behavior, homework and physical activity. During these hours, engagement in
      physical activity does not appear to displace time spent doing homework.

PMID- 19168922
TI  - Effect of rest interval length on bench press performance in boys, teens, and
      men.
AB  - The purpose of this study was to assess the lifting performance of boys (N = 12;
      age 11.3 +/- 0.8 yr), teens (N = 13; age 13.6 +/- 0.6 yr), and men (N = 17; age
      21.4 +/- 2.1 yr) to various rest interval (RI) lengths on the bench press
      exercise. Each subject performed 3 sets with a 10 repetition maximum load and a
      1, 2, and 3 min RI between sets. Significant differences in lifting performance
      between age groups were observed within each RI for selected sets with boys and
      teens performing significantly more total repetitions than adults following
      protocols with 1 min (27.9 +/- 3.1, 26.9 +/- 3.9, and 18.2 +/- 4.1,
      respectively), 2 min (29.6 +/- 1.0, 27.8 +/- 3.5, and 21.4 +/- .1, respectively)
      and 3 min (30.0 +/- 0.0, 28.8 +/- 2.4, and 23.9 +/- 5.3, respectively) RIs.
      Significant differences in average velocity and average power between age groups
      were also observed. These findings indicate that boys and teens are better able
      to maintain muscle performance during intermittent moderate-intensity resistance
      exercise as compared with men.

PMID- 19168923
TI  - Live high + train low: thinking in terms of an optimal hypoxic dose.
AB  - "Live high-train low" (LH+TL) altitude training allows athletes to "live high"
      for the purpose of facilitating altitude acclimatization, as characterized by a
      significant and sustained increase in endogenous erythropoietin and subsequent
      increase in erythrocyte volume, while simultaneously enabling them to "train low"
      for the purpose of replicating sea-level training intensity and oxygen flux,
      thereby inducing beneficial metabolic and neuromuscular adaptations. In addition
      to natural/terrestrial LH+TL, several simulated LH+TL devices have been developed
      including nitrogen apartments, hypoxic tents, and hypoxicator devices. One of the
      key issues regarding the practical application of LH+TL is what the optimal
      hypoxic dose is that is needed to facilitate altitude acclimatization and produce
      the expected beneficial physiological responses and sea-level performance
      effects. The purpose of this review is to examine this issue from a research
      based and applied perspective by addressing the following questions: What is the
      optimal altitude at which to live, how many days are required at altitude, and
      how many hours per day are required? It appears that for athletes to derive the
      hematological benefits of LH+TL while using natural/terrestrial altitude, they
      need to live at an elevation of 2000 to 2500 m for =4 wk for =22 h/d. For
      athletes using LH+TL in a simulated altitude environment, fewer hours (12-16 h)
      of hypoxic exposure might be necessary, but a higher elevation (2500 to 3000 m)
      is required to achieve similar physiological responses.

PMID- 19168924
TI  - Acute effects of soccer training on white blood cell count in elite female
      players.
AB  - PURPOSE: To investigate the acute changes in leukocyte number and cortisol after
      a single bout of soccer training. METHODS: Ten elite female national-team soccer
      players and 8 nonathletes participated in the study. The duration of the exercise
      was 2 h, and it was performed at an intensity of 75% of maximal heart rate
      (HRmax). Blood samples were taken before, immediately after, and 4 h after a
      soccer training session to determine total white blood cells; the subsets of
      neutrophils, lymphocytes, monocytes, eosinophils, and basophils; and cortisol. At
      the same time, blood samples were obtained from nonathletes who refrained from
      exercise. RESULTS: Data analysis indicated a significant increase in total white
      blood cells in the athletes postexercise (P < .001). The leukocytosis was still
      evident after 4 h of recovery (78% higher than the preexercise values), and there
      was a significant difference between athletes and nonathletes (P < .001). This
      leukocytosis was primarily caused by neutrophilia-there were no significant
      differences in lymphocytes after the end of exercise or between the 2 groups (P >
      0.05). In addition, there was a statistically significant difference in cortisol
      concentration between athletes and nonathletes after the exercise (P < .001).
      CONCLUSION: These findings revealed that the single bout of soccer training at an
      intensity of 75% of HRmax induced leukocytosis without affecting the lymphocyte
      count in elite female athletes and probably the effectiveness of cellular
      components of adaptive immunity. Coaches should provide adequate time (>4 h)
      until the next exercise session.

PMID- 19168925
TI  - Effects of caffeine on repetitions to failure and ratings of perceived exertion
      during resistance training.
AB  - CONTEXT: Ergogenic effects of caffeine on aerobic or endurance exercise are well
      documented. Conversely, the ergogenic value of caffeine on high-intensity,
      primarily anaerobic performance is not well understood even though the proposed
      mechanisms of action for caffeine permit a strong theoretical basis for
      application to this type of exercise. PURPOSE: This study examined effects of
      caffeine (Ca) on number repetitions (reps), ratings of perceived exertion (RPE),
      and peak heart rate (PHR) during resistance-training exercise with reps performed
      to volitional failure. METHODS: Subjects (N = 17) were tested for 10-rep maximum
      in bench press (BP) and leg press (LP). In sessions 2 and 3, Ca (approximately 6
      mg/kg) or placebo (Pl) was ingested 1 hr beforehand in a double-blind manner and
      counterbalanced order. Subjects performed 3 sets to failure (BP and LP) with
      reps, PHR, and RPE recorded each set. Repeated-measures ANOVAs, 2 (trial) x 3
      (set), were used to analyze dependent measures with the Tukey honestly
      significant difference used when necessary as the post hoc test. RESULTS: In BP,
      no significant differences (Ca vs Pl) were observed (reps, RPE, PHR). During set
      3 of LP training, Ca was associated with significantly higher reps (12.5 +/- 4.2
      vs 9.9 +/- 2.6) and PHR (158.5 +/- 11.9 vs 151.8 +/- 13.2). No significant RPE
      differences were found during LP. CONCLUSIONS: The findings of similar RPE
      concurrent with higher reps suggest that caffeine can blunt pain responses,
      possibly delaying fatigue in high-intensity resistance training. Ergogenic
      effects might be limited to the later sets in a resistance-training session.
      Further research is warranted regarding ergogenic effects of caffeine during
      resistance training and potential mechanisms of action.

PMID- 19168926
TI  - Optimal loading for peak power output during the hang power clean in professional
      rugby players.
AB  - PURPOSE: The ability to develop high levels of muscle power is considered an
      essential component of success in many sporting activities; however, the optimal
      load for the development of peak power during training remains controversial. The
      aim of the present study was to determine the optimal load required to observe
      peak power output (PPO) during the hang power clean in professional rugby
      players. METHODS: Twelve professional rugby players performed hang power cleans
      on a portable force platform at loads of 30%, 40%, 50%, 60%, 70%, 80%, and 90% of
      their predetermined 1-repetition maximum (1-RM) in a randomized and balanced
      order. RESULTS: Relative load had a significant effect on power output, with peak
      values being obtained at 80% of the subjects' 1-RM (4466 +/- 477 W; P < .001).
      There was no significant difference, however, between the power outputs at 50%,
      60%, 70%, or 90% 1-RM compared with 80% 1-RM. Peak force was produced at 90% 1-RM
      with relative load having a significant effect on this variable; however,
      relative load had no effect on peak rate of force development or velocity during
      the hang power clean. CONCLUSIONS: The authors conclude that relative load has a
      significant effect on PPO during the hang power clean: Although PPO was obtained
      at 80% 1-RM, there was no significant difference between the loads ranging from
      40% to 90% 1-RM. Individual determination of the optimal load for PPO is
      necessary in order to enhance individual training effects.

PMID- 19168927
TI  - Validity and reproducibility of the ErgomoPro power meter compared with the SRM
      and Powertap power meters.
AB  - PURPOSE: The ErgomoPro (EP) is a power meter that measures power output (PO)
      during outdoor and indoor cycling via 2 optoelectronic sensors located in the
      bottom bracket axis. The aim of this study was to determine the validity and the
      reproducibility of the EP compared with the SRM crank set and Powertap hub (PT).
      METHODS: The validity of the EP was tested in the laboratory during 8 submaximal
      incremental tests (PO: 100 to 400 W), eight 30-min submaximal constant-power
      tests (PO = 180 W), and 8 sprint tests (PO > 750 W) and in the field during 8
      training sessions (time: 181 +/- 73 min; PO: approximately 140 to 160 W). The
      reproducibility was assessed by calculating the coefficient of PO variation (CV)
      during the submaximal incremental and constant tests. RESULTS: The EP provided a
      significantly higher PO than the SRM and PT during the submaximal incremental
      test: The mean PO differences were +6.3% +/- 2.5% and +11.1% +/- 2.1%
      respectively. The difference was greater during field training sessions (+12.0%
      +/- 5.7% and +16.5% +/- 5.9%) but lower during sprint tests (+1.6% +/- 2.5% and
      +3.2% +/- 2.7%). The reproducibility of the EP is lower than those of the SRM and
      PT (CV = 4.1% +/- 1.8%, 1.9% +/- 0.4%, and 2.1% +/- 0.8%, respectively).
      CONCLUSIONS: The EP power meter appears less valid and reliable than the SRM and
      PT systems.

PMID- 19168928
TI  - Physical characteristics and incidence of injuries in adult figure skaters.
AB  - PURPOSE: To examine relationships between physical characteristics and injuries
      in adult figure skaters. METHODS: One hundred thirty adult figure skaters (113
      women and 17 men, 43 +/- 9 and 55 +/- 10 y old, respectively) completed study
      questionnaires concerning health, height and weight, exercise habits, and
      injuries in the preceding year. RESULTS: The men were older and taller and
      weighed more than the women (P < .05). Approximately 80% had normal body-mass
      index (BMI, weight [kg]/height [m]2), and the other 20% were overweight or obese
      based on BMI. Study participants had been skating for 12 +/- 10 y (range 1 to 68
      y). Most skate 4 to 5 h/wk (competitive > recreational skaters, P < .05).
      Although approximately 50% of competitive skaters always warm up or stretch
      before skating, less than 30% of the recreational skaters always do so (P < .05).
      Seventy-two skaters (56%) reported at least 1 injury in the preceding year. Most
      of the injuries were acute injuries to the lower extremity and were related to
      skating (76%). There were no differences in the incidence of stretching or warm
      up activities or the number of hours per week spent skating in those who had
      incurred a skating-related injury compared with those who had not been injured (P
      > .05). CONCLUSIONS: The results suggest that adult skaters have training and
      exercise habits that might increase their risk of injury and impair athletic
      performance. This suggests the importance of educational programming for adult
      skaters designed to address injury prevention and basic exercise-training
      principles.

PMID- 19168929
TI  - Development of a repeated-effort test for elite men's volleyball.
AB  - PURPOSE: The authors conducted a study to develop a repeated-effort test for
      international men's volleyball. The test involved jumping and movement activity
      that was specific to volleyball, using durations and rest periods that replicated
      the demands of a match. METHODS: A time-motion analysis was performed on a
      national team and development national team during international matches to
      determine the demands of competition and thereby form the basis of the rationale
      in designing the repeated-effort test. An evaluation of the test for reliability
      and validity in discriminating between elite and sub-elite players was performed.
      RESULTS: The test jump height and movement-speed test parameters were highly
      reliable, with findings of high intraclass correlations (ICCs) and low typical
      errors of measurement (TE; ICC .93 to .95 and %TE 0.54 to 2.44). The national
      team's ideal and actual jump height and ideal and actual speeds, mean +/- SD,
      were 336.88 +/- 8.31 cm, 329.91 +/- 6.70 cm, 6.83 +/- 0.34 s, and 7.14 +/- 0.34
      s, respectively. The development national team's ideal and actual jump heights
      and ideal and actual speeds were 330.88 +/- 9.09 cm, 323.80 +/- 7.74 cm, 7.41 +/-
      0.56 s, and 7.66 +/- 0.56 s, respectively. Probabilities of differences between
      groups for ideal jump, actual jump, ideal time, and actual time were 82%, 95%,
      92%, and 96%, respectively, with a Cohen effect-size statistic supporting large
      magnitudes (0.69, 0.84, 1.34, and 1.13, respectively). CONCLUSION: The results of
      this study demonstrate that the developed test offers a reliable and valid method
      of assessing repeated-effort ability in volleyball players.

PMID- 19168930
TI  - Using absolute and relative muscle endurance to estimate maximal strength in
      young athletes.
AB  - PURPOSE: The purpose of this study was to evaluate the effectiveness of
      repetitions to fatigue (RTF) using absolute and relative muscle-endurance
      performances to estimate 1-repetition-maximum (1-RM) bench-press performance in
      high school male athletes. METHODS: Members of high school athletic teams (n =
      118, age = 16.5 +/- 1.1 y, weight = 82.7 +/- 18.7 kg) were tested for 1-RM bench
      press and RTF with an absolute load of 61.4 kg and a relative load that produced
      7 to 10 RTF (7- to 10-RM). All participants had completed a minimum of 4 wk of
      resistance training before measurement. RESULTS: All 7- to 10-RM-prediction
      equations had higher correlations between predicted and actual 1-RM (r > .98)
      than the 61.4-kg absolute-load equation (r = .95). Despite the high correlations,
      only 3 of 11 equations produced predicted values that were nonsignificantly
      different from actual 1-RM. The best 7-to 10-RM equation predicted 65% of the
      athletes'performances within +/-4.5 kg of their actual 1-RM. The addition of
      simple anthropometric dimensions did not increase the validity correlations or
      decrease the prediction errors. CONCLUSION: The 7- to 10-RM method can provide an
      accurate method of estimating strength levels for adjusting loads in a training
      program and is more accurate for predicting 1-RM bench press in high school
      athletes than the 61.4-kg repetition method.

PMID- 19168931
TI  - The relationships between science and sport: application in triathlon.
AB  - The relationships between sport sciences and sports are complex and changeable,
      and it is not clear how they reciprocally influence each other. By looking at the
      relationship between sport sciences and the "new" (~30-year-old) sport of
      triathlon, together with changes in scientific fields or topics that have
      occurred between 1984 and 2006 (278 publications), one observes that the change
      in the sport itself (eg, distance of the events, wetsuit, and drafting) can
      influence the specific focus of investigation. The sport-scientific fraternity
      has successfully used triathlon as a model of prolonged strenuous competition to
      investigate acute physiological adaptations and trauma, as support for better
      understanding cross-training effects, and, more recently, as a competitive sport
      with specific demands and physiological features. This commentary discusses the
      evolution of the scientific study of triathlon and how the development of the
      sport has affected the nature of scientific investigation directly related to
      triathlon and endurance sport in general.

PMID- 19168932
TI  - The time course for changes in plasma [h+] after sodium bicarbonate ingestion.

PMID- 19168933
TI  - Variability of erythropoietin response to sleeping at simulated altitude: a
      cycling case study.

PMID- 19168934
TI  - Individualized aerobic-power training in an underperforming youth elite
      association football player.
AB  - A 7-week, 10-session individual training program was implemented with a youth
      elite football (soccer) player who had been underperforming because of poor
      aerobic fitness. The intervention focused on developing aerobic power and high
      lactate production and contributed to a 32.3% improvement in a football-specific
      performance test. The player was able to return to play and exceed expected
      performance levels during competitive match play.

PMID- 19168935
TI  - The burden of prenatal exposure to alcohol: revised measurement of cost.
AB  - BACKGROUND: In Canada the incidence of Fetal Alcohol Spectrum Disorder (FASD) is
      estimated to be 1 in 100 live births. FASD is the leading cause of developmental
      and cognitive disabilities in Canada. Only one study has examined the cost of
      FASD in Canada. In that study we did not include prospective data for infants
      under the age of one year, costs for adults beyond 21 years or costs for
      individuals living in institutions. OBJECTIVE: To calculate a revised estimate of
      direct and indirect costs associated with FASD at the patient level. METHODS:
      Cross-sectional study design was used. Two-hundred and fifty (250) participants
      completed the study tool. Participants included caregivers of children, youth and
      adults, with FASD, from day of birth to 53 years, living in urban and rural
      communities throughout Canada participated. Participants completed the Health
      Services Utilization Inventory (HSUI). Key cost components were elicited: direct
      costs: medical, education, social services, out-of-pocket costs; and indirect
      costs: productivity losses. Total average costs per individual with FASD were
      calculated by summing the costs for each in each cost component, and dividing by
      the sample size. Costs were extrapolated to one year. A stepwise multiple
      regression analysis was used to identify significant determinants of costs and to
      calculate the adjusted annual costs associated with FASD. RESULTS: Total adjusted
      annual costs associated with FASD at the individual level was $21,642 (95% CI,
      $19,842; $24,041), compared to $14,342 (95% CI, $12,986; $15,698) in the first
      study. Severity of the individual's condition, age, and relationship of the
      individual to the caregiver (biological, adoptive, foster) were significant
      determinants of costs (p < 0.001). Cost of FASD annually to Canada of those from
      day of birth to 53 years old, was $5.3 billion (95% CI, $4.12 billion; $6.4
      billion). CONCLUSIONS: Study results demonstrated the cost burden of FASD in
      Canada was profound. Inclusion of infants aged 0 to 1 years, adults beyond the
      age of 21 years and costs associated with residing in institutions provided a
      more accurate estimate of the costs of FASD. Implications for practice, policy,
      and research are discussed. Key words: Alcohol, pregnancy, cost, economic burden,
      fetal alcohol spectrum disorder.

PMID- 19168936
TI  - A faster ordered-subset convex algorithm for iterative reconstruction in a
      rotation-free micro-CT system.
AB  - We present a faster iterative reconstruction algorithm based on the ordered
      subset convex (OSC) algorithm for transmission CT. The OSC algorithm was modified
      such that it calculates the normalization term before the iterative process in
      order to save computational cost. The modified version requires only one
      backprojection per iteration as compared to two required for the original OSC. We
      applied the modified OSC (MOSC) algorithm to a rotation-free micro-CT system that
      we proposed previously, observed its performance, and compared with the OSC
      algorithm for 3D cone-beam reconstruction. Measurements on the reconstructed
      images as well as the point spread functions show that MOSC is quite similar to
      OSC; in noise-resolution trade-off, MOSC is comparable with OSC in a regular
      noise situation and it is slightly worse than OSC in an extremely high-noise
      situation. The timing record shows that MOSC saves 25-30% CPU time, depending on
      the number of iterations used. We conclude that the MOSC algorithm is more
      efficient than OSC and provides comparable images.

PMID- 19168937
TI  - Evaluation of an Epson flatbed scanner to read Gafchromic EBT films for radiation
      dosimetry.
AB  - Gafchromic EBT (EBT) films are becoming increasingly popular due to their
      advantageous properties. When flatbed colour scanners are used for film
      dosimetry, a good quality control of the scanning device is a crucial step for
      accurate results. The proposal of this work was to fully assess the performance
      of the scanner Epson Expression 10000XL in order to quantify all parameters and
      needed corrections to minimize dose uncertainties. A standard step tablet, with
      32 steps and optical densities from 0.06 to 3.8, was used to check the scanner
      linearity. The scanner warming-up effect and reproducibility were evaluated by
      performing 30 consecutive scans plus 20 scans in 15 min intervals. The scanning
      colour modes: 24 and 48 bits and scanning resolutions from 50 to 300 dpi were
      tested. A Wiener filter with different pixels regions was applied with the
      purpose of reducing the film noise. All scans were made in transmission mode with
      a constant film orientation. The red colour channel was posteriorly extracted
      from the images to maximize readout sensitivity. Two EBT films were irradiated,
      perpendicularly and parallel to beam incidence, with a 6 MV photon beam with
      doses that ranged from 0.2 to 3 Gy. A polynomial expression was used to convert
      optical density into dose. Dose uncertainty was quantified applying error
      propagation analysis. A correction for the non-uniform response of the scanner
      was determined using five films irradiated with a uniform dose. The scanner
      response was linear until an optical density of approximately 1 which corresponds
      to doses higher than those of clinical interest for EBT films. The scanner signal
      stabilized after seven readings. Scanner reproducibility around 0.2% was obtained
      either with the scanner warm or cold. However, reproducibility was significantly
      reduced when comparing images digitized with the scanner at different
      temperatures. Neither the colour depth mode, the scanning resolution, the
      multiscan option nor the Wiener filter had a significant effect on the shape of
      the calibration curve. However, a reduction in dose uncertainty was possible by
      selecting appropriate reading parameters. These are a 48 bit colour depth, a 75
      dpi resolution and repeating the scan four times. Finally, the two dimensional
      Wiener filter applied to a 3 x 3 pixel region to the red component of the image
      reduced the experimental scan uncertainty to about 0.5% for doses higher than 0.5
      Gy. Total scan uncertainty was less than 2% for a perpendicular calibration and
      reduced to less than 1% for a parallel calibration. A dose over-estimation of
      around 5% for clinical doses may be made if the image acquired is not corrected
      for the non-uniform response of the scanner. A protocol to read EBT films using
      the Epson Expression 10000XL scanner was established for IMRT verification. The
      contribution for the overall uncertainty in film dosimetry coming from the
      scanning process was estimated to be around 0.5% for doses higher than 0.5 Gy
      when reading parameters are optimized. Total scan uncertainty achieved is about
      2% when using a perpendicular calibration. It can further be reduced if a
      parallel calibration is used.

PMID- 19168938
TI  - In vivo high-resolution 3D photoacoustic imaging of superficial vascular anatomy.
AB  - The application of a photoacoustic imaging instrument based upon a Fabry-Perot
      polymer film ultrasound sensor to imaging the superficial vasculature is
      described. This approach provides a backward mode-sensing configuration that has
      the potential to overcome the limitations of current piezoelectric based
      detection systems used in superficial photoacoustic imaging. The system has been
      evaluated by obtaining non-invasive images of the vasculature in human and mouse
      skin as well as mouse models of human colorectal tumours. These studies showed
      that the system can provide high-resolution 3D images of vascular structures to
      depths of up to 5 mm. It is considered that this type of instrument may find a
      role in the clinical assessment of conditions characterized by changes in the
      vasculature such as skin tumours and superficial soft tissue damage due to burns,
      wounds or ulceration. It may also find application in the characterization of
      small animal cancer models where it is important to follow the tumour vasculature
      over time in order to study its development and/or response to therapy.

PMID- 19168939
TI  - The effect of a compression paddle on energy response, calibration and
      measurement with mammographic dosimeters using ionization chambers and solid
      state detectors.
AB  - A compression paddle is always used in mammography x-ray examinations, in order
      to improve image quality and reduce patient doses. Although clinical dose
      measurements should be performed with the paddle to interfere with the x-ray
      beam, calibration of mammography dosimeters is performed free in air without the
      presence of the paddle. The paddle hardens the x-ray beam, which has an impact on
      a dosimeter performance, particularly on high-energy-dependent detectors. Due to
      the paddle, clinical mammography x-ray systems may exhibit beams with HVL values
      exceeding those of the IEC 61267 RQR-M series qualities at which dosimeters are
      usually calibrated. In this study, the influence of the paddle in mammography
      dosimetry is examined, in Mo/Mo anode/filter x-ray qualities. PMMA slabs of 1, 2
      and 3 mm thickness and Al foils of 0.05, 0.10 and 0.15 mm thicknesses were used
      to simulate the paddles, producing beams with HVL values from 0.28 up to 0.43
      mmAl. In these qualities, four solid-state (ST) detectors and three ionizations
      chambers (IC) were calibrated in terms of Kair and N(K) and k(Q) were deduced.
      The results showed that all IC and two modern-type ST dosimeters have a flat
      energy response in the above HVL range (less than 3%), so their calibration
      factor at RQR-M2 quality could be safely used for clinical measurements. Two
      other ST dosimeters exhibit up to 20% energy response, so differences up to 15%
      in dose measurement may be observed if the effect of paddle on their performance
      is ignored. Finally, the need of additional mammographic calibration qualities to
      the existing IEC 61267 RQR-M series is examined and discussed.

PMID- 19168940
TI  - Darwinism and the cultural evolution of sports.
AB  - This article outlines a Darwinian approach to sports that takes into account its
      profoundly cultural character and thereby overcomes the traditional nature
      culture dichotomies in the sociology of sport. We argue that there are good
      reasons to view sports as culturally evolved signaling systems that serve a
      function similar to (biological) courtship rituals in other animals. Our approach
      combines the insights of evolutionary psychology, which states that biological
      adaptations determine the boundaries for the types of sport that are possible,
      and pure cultural theories, which describe the mechanism of cultural evolution
      without referring to sport's biological bases. Several biological and cultural
      factors may moderate the direct effect that signaling value has on a sport's
      viability or popularity. Social learning underlies many aspects of the cultural
      control of sports, and sports have evolved new cultural functions more-or-less
      unrelated to mate choice as cultural evolution itself became important in humans.

PMID- 19168941
TI  - Kawasaki disease in India: increasing awareness or increased incidence?
AB  - Reports of Kawasaki disease (KD) throughout India are increasing. This article
      addresses the question of whether the increased diagnosis of KD in India
      represents the emerging recognition of an illness that had been previously
      obscured by misdiagnosis, or whether KD is new to India and is increasing in
      incidence.Whichever answer turns out to be correct, the burden of KD is likely to
      pose a significant challenge to the health-care system in India in the coming
      years, due to the high cost of treatment and the potential for lifelong
      cardiovascular sequelae.Moreover, elucidating the factors that have contributed
      to the increased recognition of KD in India may provide useful insights for the
      continuing search for the etiology of KD worldwide.

PMID- 19168942
TI  - Personal morality and professional obligations: rights of conscience and informed
      consent.
AB  - This article examines the issue of expanding rights of conscience for health-care
      professionals to include rights grounded in claims of complicity. Our concerns
      relate to the nature of professional expertise, on the one hand, and an
      individual's right to live by his or her values, on the other. The fact that a
      patient is dependent on a physician's counseling about treatment options requires
      limiting conscience-based refusal to provide information, since allowing refusal
      would deprive patients of even knowing the options that exist for them.
      Sanctioning such claims of conscience not only would supplant one person's moral
      judgment with another's, it would also allow professional standing to be used as
      a justification for imposing one person's moral views on another.

PMID- 19168943
TI  - Creating reflective spaces: interactions between philosophers and biomedical
      scientists.
AB  - New science policy initiatives are encouraging multidisciplinary collaborations
      between social scientists, humanists, biomedical scientists, and engineers.
      Although these policy initiatives are not always clear about how such
      interactions should take place, the idea is that social scientists and humanists
      can bring a broader perspective to the table, as well as highlight a variety of
      matters that are often not addressed by natural scientists and engineers. This
      article focuses on collaborations between philosophers and biomedical scientists
      in order to discuss how interdisciplinary collaborations may address ethical,
      social, and environmental concerns in ways that lead to improvements in people's
      health and quality of life. The article concludes with a consideration of some of
      the challenges that such collaborations face.

PMID- 19168944
TI  - Who is Durer's "Syphilitic Man"?
AB  - Among Albrecht Durer's first known woodcuts is one showing a syphilitic man. The
      Nuremberg artist's image is the earliest known depiction of an individual
      suffering from this illness. Syphilis was probably brought by Conquistadores from
      the New World to Naples in the later 1490s and was then transmitted throughout
      Western Europe by Northern mercenaries (Landsknechten) returning from Italy to
      their native Germany and Switzerland. The attire worn by Durer's Syphilitic Man
      is exactly that of the Landsknecht. This makes the image important not only as a
      very early work by the artist and the earliest image of a syphilitic, but also as
      a depiction of the agent of the disease. The young Durer had ample opportunity to
      study such mercenaries during his journeyman years in present-day Switzerland and
      Strasbourg, since most of them came from precisely the same impoverished
      territories.

PMID- 19168945
TI  - Edward Bancroft's "Torporific Eels".
AB  - Edward Bancroft was a medical apprentice in Connecticut before running off to
      Guiana in 1763. While in South America, he practiced medicine and collected
      material for a lengthy book on the region, which he published after he settled in
      London. Bancroft's Essay (1769) contains a description of the "torporific eels"
      found in the warm rivers of Guiana, along with a series of experiments suggesting
      that the eel's powers are electrical. It also calls for studies to determine
      whether saltwater torpedo rays might demonstrate the same properties, which
      Bancroft expected would be the case. Today, Bancroft is best remembered for
      serving Benjamin Franklin and the American delegation in France during the War of
      Independence, and for being a double agent. But what this colorful man wrote
      about the South American eels helped to make an early case for animal electricity
      and stimulated Franklin to encourage John Walsh to conduct his landmark
      electrical experiments on torpedoes and electric eels in the 1770s. These efforts
      led to new way of thinking about the physiology of the nervous and muscular
      systems, even in nonspecialized fish.

PMID- 19168946
TI  - Poetry and the brain: Cajal's conjectures on the psychology of writers.
AB  - In 1902, Santiago Ramon y Cajal (1852-1934), the father of modern neuroscience
      and a 1906 Nobel laureate, contributed a preface to a book of poems by his fellow
      countryman, Spanish poet and dramatist Marcos Zapata (1844-1914). In that
      uncustomary-for his neuroscience followers-essay, Cajal unfolds his ideas on the
      literary genres of drama and comedy in relation to the workings of the human mind
      and sentiments. The same text was reissued almost half a century later in Spain
      and in Argentina under the title The Psychology of Artists. We present an English
      version of Cajal's essay, which may be of interest to both humanists and
      biologists, and which further denotes the celebrated neuroanatomist's attempt at
      understanding the mystery of the human mind.

PMID- 19168947
TI  - Medical education and the tyranny of competency.
AB  - Those who educate medical students and physicians work in a world suffused with
      the concept of competency. This article examines the intellectual origins and
      hidden assumptions of this concept and argues that it is an inadequate, and even
      harmful, concept to use as a guiding motif for professional education. The
      competency model-which tends to be top-down and prescriptive-does not provide the
      framework for objective educational assessment that it claims to provide. The
      alternative apprenticeship model is more appropriate for professional education
      and is more consistent with what psychological research has shown about the
      acquisition of expertise.

PMID- 19168948
TI  - Death, mourning, and medical progress.
AB  - A number of changes can be observed in the way people are coming to think about
      death, mourning, and medical progress. The palliative care movement was initiated
      some 30 years ago to respond to widespread ignorance or neglect of pain relief
      for the dying, which was then coming to public attention and becoming a key part
      of the nascent hospice movement. Yet if an important feature of the latter
      movement was acceptance of the reality of death, in recent years there has
      emerged a blending of clinical treatment and hospice care, a kind of compromise
      with the idea of death as an inevitability. Meanwhile, the combination of real
      progress in forestalling death and the matching medical and media hype about past
      and coming victories over mortality mean that death itself is coming to be seen
      as a biological accident, a contingent event, not a fixed given. People die now
      because of bad luck, indifference to good living habits, unfortunate genetics,
      and the like, or because they have the misfortune of dying before a cure for
      their fatal disease is at hand. Mourning likewise is changing. The old custom of
      the deceased being laid out in their living rooms, followed by a funeral, has
      long given way to a movement away from public funerals to private ones followed
      later by a memorial ceremony. No more dead bodies on display to grieve over, but
      soothing ceremonies of remembrance.

PMID- 19168949
TI  - The threat that dare not speak its name: human extinction.
AB  - The end of the human race is not imminent, but it is both inevitable and
      important. Judging by the scarcity of relevant publications, however, there seems
      little public or professional concern about this prospect. We submit that this
      striking disinterest reflects a combination of ignorance and denial that is
      putting the long-term interests of society in jeopardy. With the pace of change
      now outstripping that of adaptation, it is no longer alarmist for academics to
      raise awareness about the approach of human extinction and to design strategies
      by which time to extinction might be prolonged. By making complacent and
      anthropocentric thinking less politically correct than it is at present, such
      awareness could motivate the world community to reformulate social norms in a way
      that benefits our descendants as much as possible for as long as possible.

PMID- 19168950
TI  - Early detection of systemic candidiasis in the whole blood of patients with
      hematologic malignancies.
AB  - Systemic candidiasis is a significant cause of morbidity and mortality in
      patients with hematologic disorders. The aim of this study was to determine the
      prevalence of systemic candidiasis and the efficiency of the polymerase chain
      reaction-enzyme-linked immunosorbent assay (PCR-ELIZA) method for the early
      detection of Candida spp. in patients with hematologic malignancies. From 2004 to
      2006, 194 patients with hematologic malignancies were evaluated for systemic
      candidiasis. Collected blood samples were assayed using the PCR-ELISA method for
      the presence of the bands on ethidium bromide stained gel, and for hybridization
      with Candida spp. as well. The female-to-male ratio was 61:133, the mean age was
      33.7 years, and the mean hospitalization period was 21.2 days. Twenty-five
      patients (12.9%) had positive PCR-ELISA results for systemic candidiasis. The
      etiologic agents were Candida albicans (21 cases), C. tropicalis (3 cases), and
      C. krusei (1 case). The mean interval of PCR-ELISA positivity in blood samples
      before the manifestation of clinical signs was 12.6 days. Fungal PCR-ELISA assay
      became negative after 14 days when patients were treated successfully with
      amphotericin B, and the assay remained positive until death when the treatment
      failed. The PCR-ELISA method can potentially serve as a useful tool for the
      management of patients suffering from hematologic malignancies and at risk for
      systemic candidiasis.

PMID- 19168951
TI  - Expression and DNA microarray analysis of a platelet activating factor-related
      molecule in severe pneumonia in mice due to influenza virus and bacterial co
      infection.
AB  - Platelet-activating factor (PAF) is a critical mediator of severe inflammatory
      diseases such as pneumonia, and the PAF-receptor (PAFR) is known to be an anchor
      for Streptococcus pneumoniae attachment to lung epithelial cells. We conducted a
      DNA microarray analysis to detect critical factors that mediate fulminant
      pneumonia due to influenza virus and S. pneumoniae co-infection in mice. Among
      the factors detected, levels of PAF-acetyl hydrolase (PAF-AH), which functions as
      inactivated PAF, were significantly increased, and PAFR was expressed in co
      infected mouse lungs, as compared to the respective levels in mice infected with
      either S. pneumoniae or virus alone. Significantly elevated PAF-AH enzymatic
      activity was observed in the co-infected mouse lung, suggesting that co-infection
      activated PAF-related factors. These findings suggest that PAF and related
      molecules play important roles in fulminant pneumonia due to influenza virus
      infection, especially when severe bacterial pneumonia is complicated by co
      infection with influenza virus.

PMID- 19168952
TI  - Evaluation of the efficacy of ribavirin therapy on survival of Crimean-Congo
      hemorrhagic fever patients: a case-control study.
AB  - The mortality rate resulting from Crimean-Congo hemorrhagic fever (CCHF) has been
      reported in different epidemics to range from 5% to more than 70%. While
      ribavirin has been recommended as the drug of choice in the treatment of CCHF, no
      consistent study has unequivocally demonstrated its effectiveness. Using the case
      control method, we attempted to evaluate the efficacy of ribavirin in reducing
      mortality among CCHF cases admitted to Boo-Ali Educational Hospital in Zahedan,
      Iran, during the years 2000 to 2006. Sixteen deaths among CCHF cases were
      compared with 47 cases of survival. All patients had a definitive diagnosis based
      on the results of IgG and IgM capture ELISA tests recorded in their files.
      Ribavirin therapy for patients who survived had begun on average approximately 24
      h earlier than the initiation of ribavirin therapy in the cases of death
      (P=0.033), and about 2 days earlier in non-bleeding survivors than in bleeding
      survivors (P=0.013). Based on the results of a multivariable analysis, the most
      important variables found to enhance survival were the time interval between the
      disease onset and ribavirin prescription (P=0.004), the time interval between
      bleeding onset and ribavirin prescription (P=0.037), and the time interval
      between disease onset and bleeding onset (P=0.014). Based on our findings,
      ribavirin appears to exert a marked effect on disease outcome, especially when it
      is prescribed within the first 4 days of the disease.

PMID- 19168953
TI  - Characterization of virulence genes of non-O157 Shiga toxin-producing Escherichia
      coli isolates from two provinces of Iran.
AB  - Shiga toxin-producing Escherichia coli (STEC) include O157:H7 and non-O157
      serotypes. The public health impact of STEC infections is high because of their
      ability to cause severe infections. We characterized our STEC strains isolated
      from diarrheal and asymptomatic persons in northern and southwest Iran. The 29
      STEC strains were examined for the presence of virulence genes by polymerase
      chain reaction (PCR) and their H type was analyzed by PCR-restriction fragment
      length polymorphism (RFLP) of the fliC gene. Moreover, the adherence properties
      of these strains were checked by HeLa cell adherence assay. The presence of non
      O157 isolates under these conditions was again verified. The stx1 gene was
      present in 93% of the isolates, and the gene encoding intimin (eae) was not found
      to be present among the isolates. Almost all of the STEC isolates, with the
      exception of three, were non-adherent upon tissue culture assay. The serogrouping
      revealed the presence of seven different O types among non-O157 isolates. PCR
      RFLP results for the fliC gene and classical serology examination with H antisera
      indicated the presence of nine different H types. In this study, three new
      serotypes of non-O157:H7 (i.e., O25:H3, O85:H32, and O162:H21) were found to be
      Shiga toxin producers. These findings reconfirm the results of our previously
      reported studies showing that non-O157:H7 serotypes are more prevalent under the
      present conditions. More detailed characterization of these isolates will require
      additional genetic studies.

PMID- 19168954
TI  - Evaluation of a new rapid molecular diagnostic system for Plasmodium falciparum
      combined with DNA filter paper, loop-mediated isothermal amplification, and
      melting curve analysis.
AB  - Falciparum malaria is a fatal infection without immediate diagnosability or
      treatment. There are shortages of clinicians and examiners skilled in the
      treatment of malaria in non-endemic countries, including Japan. This study was
      performed to evaluate a novel rapid molecular diagnostic system consisting of
      loop-mediated isothermal amplification (LAMP) combined with DNA filter paper (FTA
      card) and melting curve analysis. Combining LAMP with melting curve analysis
      enabled diagnosis of Plasmodium falciparum more accurately with relative ease.
      FTA cards could be used to clarify problems regarding storage, infectivity, and
      transportation. The LAMP assay was carried out at a constant temperature of 63
      degrees C for 90 min. The diagnostic system (malaria-LAMP) accurately diagnosed
      malaria (47 samples from Thailand and 50 from Zimbabwe) with 97.8% sensitivity
      and 85.7% specificity as compared with microscopic methods, indicating the
      usefulness of this combined system.

PMID- 19168955
TI  - Rv0901 from Mycobacterium tuberculosis, a possible novel virulent gene proved
      through the recombinant Mycobacterium smegmatis.
AB  - The function of protein-coding gene Rv0901 of Mycobacterium tuberculosis, which
      belongs to the cell wall and cell processes category, is not yet clear. To
      explore its features, we amplified this gene from the H37Rv genome, and His
      tagged Rv0901 protein was expressed and purified. Also, a recombinant plasmid
      bearing Rv0901 was constructed and electroporated into a virulent Mycobacterium
      smegmatis, using shuttle expression vector pMV261. Transformants were induced to
      express a predicted protein of Rv0901, identified by SDS-PAGE. Rv0901 protein and
      recombinant M. smegmatis were used to expose mammalian cells. In addition we
      studied the effect of protein or recombinant M. smegmatis on cells and in animals
      with regard to survival ratio, apoptosis ratio, quantum of nitric oxide, and
      gamma interferon. Together, gene function, protein function, and animal test
      results suggest that Rv0901 has some relationship with the virulence and
      immunogenicity of M. tuberculosis.

PMID- 19168956
TI  - Substantially exposed but HIV-negative individuals are accumulated in HIV
      serology-discordant couples diagnosed in a referral hospital in Thailand.
AB  - The objectives of this study is to characterize HIV-serology-discordant couples
      diagnosed at a referral hospital in Thailand and to identify risk factors for HIV
      transmission among married couples. Firstly, cross-sectional analysis was
      conducted from July 2000 to October 2002. Out of 216 HIV-positive married men who
      knew the HIV status of their wives, the median number of sexual contacts in 63
      men with HIV-negative wives was 6 times per month before the disclosure of HIV
      status, which did not differ from 153 men with HIV-positive wives. The majority
      of men with HIV-negative wives never used condoms. The median duration of
      marriage was 7 years for both groups. Unlike in previous reports, men with HIV
      negative wives were significantly more symptomatic (P<0.01), and their CD4+
      counts and viral loads did not differ from men with HIV-positive wives.
      Secondarily, 71 initially discordant couples were longitudinally followed until
      March 2005. Four were seroconverted out of 132.24 person-years of observation. In
      multivariate analysis incorporating sex, age, CD4+ count and sexual contact
      without a condom, shorter duration of marriage (<2 years) was found to be the
      only risk factor significantly associated with HIV transmission (hazard ratio of
      15.2, P=0.04). Individuals substantially exposed to HIV but remaining HIV
      negative are accumulated in discordant couples identified in a hospital, except
      in recently married couples.

PMID- 19168957
TI  - Mucosal vaccination approach against mosquito-borne Japanese encephalitis virus.
AB  - To investigate the potential applicability of mucosal vaccines against mucosa
      unrelated pathogens, a non-parenteral vaccination approach was taken as a
      prophylactic strategy against mosquito-borne Japanese encephalitis virus (JEV).
      Intranasal (i.n.) immunization with a mouse brain-derived formalin-inactivated JE
      vaccine induced a robust virus-neutralizing antibody in mice, and this induction
      was augmented by co-administration with cholera toxin (CT) and pertussis toxin,
      but not with killed Bordetella pertussis. The antibody response induced by the
      i.n. administration of the JE vaccine with bacterial toxins was comparable in
      intensity to that induced by a parenteral immunization regime, and the former was
      considerably more effective in terms of delayed-type hypersensitivity and local
      antibody response. In addition, the adjuvant effects of bacterial toxins were
      much more prominent for the mucosal than the parenteral route. Two other non
      invasive routes, oral and transcutaneous administration, were examined, but the
      i.n. route was by far the most effective. Finally, the vaccine efficacy of a
      chimeric fusion protein between the B subunit of CT and the JEV envelope protein
      showed some promise for the development of non-invasive JE vaccine. Our results
      suggest that the mucosal vaccination approach is feasible for a non-mucosal
      pathogen such as JEV, but that the adjuvant, carrier molecule, and administration
      route must be optimized for construction of an effective vaccine platform.

PMID- 19168958
TI  - Blood culture confirmed bacterial sepsis in neonates in a North Indian tertiary
      care center: changes over the last decade.
AB  - The spectrum of organisms causing sepsis is different in developing countries.
      Data on the recent trends of organisms causing sepsis are limited. This study was
      conducted in a tertiary care neonatal unit in Northern India. All inborn babies
      with blood-culture-positive sepsis from 1995 to 2006 were divided into two
      epochs, viz. 1995 to 1998 (epoch I) and 2001 to 2006 (epoch II). Organisms were
      grouped into early (<72 h) and late onset (> or =72 h) sepsis groups. The overall
      incidence of sepsis, the incidence of sepsis stratified by weight groups, the
      organism profile on different days of life, sepsis-related mortality and pathogen
      specific case fatality rate were calculated and compared between the two epochs.
      Out of 34,362 live births during the study period, organisms were isolated in
      1,491 neonates. Out of these, 89% had bacterial sepsis. The incidence of neonatal
      bacterial sepsis increased from epoch I to epoch II (35.8/1,000 versus 40.1/1,000
      live births, P<0.05). The incidence of early onset sepsis (EOS) did not change
      between the epochs, but the incidence of late onset sepsis (LOS) increased from
      12 to 16.5 per 1,000 live births (P<0.001). The incidence of bacterial sepsis
      decreased significantly in the 1,000- to 1,999-g birth weight groups. Klebsiella
      pneumoniae and Enterobacter aerogenes decreased, whereas Staphylococcus aureus
      increased in incidence during epoch II. Non-fermenting Gram-negative bacilli
      emerged as a newly identified pathogen during epoch II. Sepsis-associated
      mortality decreased from 42 to 20%. The incidence of bacterial sepsis has
      decreased significantly in 1,000- to 1,999-g infants, with a significant
      reduction in sepsis-related mortality. New organisms have emerged in recent
      years. The organism profile in recent years has changed, with a significant
      overlap of organisms causing EOS and LOS.

PMID- 19168959
TI  - Diarrhea as a minor adverse effect due to oral polio vaccine.
AB  - Using the adverse events monitoring system of Japan, we observed diarrhea cases
      in approximately 10% of patients who received oral poliovirus vaccine (OPV). This
      study was conducted to investigate whether diarrhea among children aged 0 to 1 is
      caused by OPV or by other factors such contact at the doctor's office and/or with
      others outside the home. We conducted a survey of the health of children after
      regular health check-ups and after the administration of the OPV. The data from
      the health check-ups were used as a control for the OPV case group. We compared
      the first-OPV dose vaccination group as well as the second-OPV dose vaccination
      group to the health check-up group. For cases of diarrhea, the odds ratio of the
      OPV group to the health check-up group was 1.776. Our findings strongly suggest
      that post-OPV cases of mild diarrhea are closely related to the administration of
      the OPV.

PMID- 19168960
TI  - An improved protocol for the preparation and restriction enzyme digestion of
      pulsed-field gel electrophoresis agarose plugs for the analysis of Legionella
      isolates.
AB  - Pulsed-field gel electrophoresis (PFGE), which determines the genomic relatedness
      of isolates, is currently used for the epidemiological investigation of
      infectious agents such as bacteria. In particular, this method has been used for
      the epidemiological investigation of Legionella outbreaks. However, it takes 4
      days to complete a Legionella-PFGE analysis. Due to partial digestion and DNA
      damage, the reproducibility of the obtained fragment digestion patterns is poor
      for this pathogen. In this study, we report an improved protocol that takes only
      2 days to complete and that allows clear discrimination of the restriction
      profile with higher reproducibility than that previously achieved.

PMID- 19168961
TI  - Cyclospora infection in an immunocompetent patient in Japan.
AB  - Cyclospora cayetanensis is a coccidian protozoa that was newly recognized in 1979
      in Papua New Guinea. We report the case of a 42-year-old French man who had
      visited Vietnam and presented with fever and watery diarrhea that had lasted for
      more than 2 weeks. The patient was diagnosed with C. cayetanensis infection by
      examination of a stool smear using UV fluorescence microscopy. Based on this rare
      case, we recommend that Cyclospora infection might be considered in the
      differential diagnosis of traveler's diarrhea in immunocompetent patients.

PMID- 19168962
TI  - Cryptococcal liver abscess: a case report of successful treatment with
      amphotericin-B and literature review.
AB  - Cryptococcus neoformans usually involves the central nervous system and the
      respiratory tract. We report a case of disseminated cryptococcosis with a liver
      abscess and meningoencephalitis in a patient with myelodysplastic syndrome.
      Computed tomography of the abdomen showed a 3-cm low-attenuated lesion in the
      left lobe of liver. Cultures from specimens of blood, the liver abscess, and the
      cerebrospinal fluid all yielded C. neoformans. The cryptococcal antigen titers
      for the serum and cerebral fluid were both 1:32. The patient was successfully
      treated with 1,335 mg of amphotericin-B followed by fluconazole. Most
      cryptococcal liver infections present as hepatitis, cholangitis, or
      microabscesses.

PMID- 19168963
TI  - An unusual respiratory syncytial virus nosocomial outbreak in an adult psychiatry
      ward.
AB  - Herein we report our experience in containing an outbreak of nosocomial
      respiratory syncytial virus (RSV) infection in a psychiatric ward in central
      Taiwan during a non-widespread RSV seasonal occurrence. A total of 8 patients and
      4 healthcare workers in the psychiatric ward developed febrile illness or upper
      respiratory tract infection symptoms between August 23 and 29, 2005. RSV was
      identified by either viral culture or reverse transcriptase-polymerase chain
      reaction (RT-PCR) assay. RSV was isolated from a symptomatic staff member (8.3%),
      and was detected in 5 (42%) by RT-PCR among 12 cases. All 5 of these RSV cases
      detected belonged to genotype A. In our experience, single cubicle isolation of
      infectious patients and a cohort of nursing care are the most important factors
      in the successful control of an RSV outbreak.

PMID- 19168964
TI  - Detection of multiple sapovirus genotypes and genogroups in oyster-associated
      outbreaks.
AB  - This report describes multiple viruses in stool specimens from oyster-associated
      gastroenteritis. Eleven outbreaks of oyster-associated gastroenteritis were
      examined for enteric viruses between January 2002 and March 2006 in Japan.
      Multiple norovirus genotypes were detected in all outbreaks; moreover, kobuvirus,
      sapovirus, and astrovirus were also detected in 6, 3, and 1 of the 11 outbreaks,
      respectively. Notably, multiple sapovirus genogroups were detected in the stool
      specimens from subjects in two oyster-associated gastroenteritis outbreaks.

PMID- 19168965
TI  - Chikungunya virus isolated in Lakshadweep islands in the Indian Ocean: evidence
      of the Central/East African genotype.
AB  - Virological investigation was carried out to determine the etiology of suspected
      Chikungunya fever among humans reported in the Lakshadweep islands in the Indian
      Ocean. Three out of 23 acute sera samples showed cytopathological changes in Vero
      cell lines. Further, indirect immunofluorescence antibody test and reverse
      transcriptase-polymerase chain reaction studies demonstrated the Chikungunya
      virus etiology during the episode. E1 gene sequence analysis has confirmed the
      involvement of the Central/East African genotype of the Chikungunya virus.

PMID- 19168966
TI  - A case of Crimean-congo hemorrhagic fever with pleural effusion.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral zoonosis with the
      potential of human-to-human transmission that affects wide areas in Asia,
      Southeastern Europe, and Africa. Hemorrhagic manifestations constitute a
      prominent symptom of late stage disease with case fatality rates from 3 to 50%.
      We present a case of CCHF complicated by hemorrhagic pleural effusion and
      resulting in resolution without chest tube drainage in a 9-year-old boy. The
      diagnosis of CCHF was confirmed by enzyme-linked immunosorbent assay tests. Both
      serum and pleural fluid CCHF IgM were positive at titers of 1/1,600 and 1/6,400,
      respectively.

PMID- 19168967
TI  - Molecular survey for Anaplasma bovis and Anaplasma phagocytophilum infection in
      cattle in a pastureland where sika deer appear in Hokkaido, Japan.
AB  - Anaplasma bovis and Anaplasma phagocytophilum infection were examined by species
      specific nested polymerase chain reaction in cattle in a pastureland where sika
      deer appear in Hokkaido, Japan. Of the 78 cattle examined, 12 (15%) and 1 (1%)
      tested positive for infection by A. bovis and A. phagocytophilum, respectively.
      One cattle tested positive for both. A. phagocytophilum infection rates were
      significantly lower in cattle than in sika deer (46%), but the infection rate by
      A. bovis was not significantly different between cattle (15%) and sika deer
      (23%). The strain of A. phagocytophilum detected in this study may possess
      significantly lower virulence or infectivity in cattle hosts. No clinical
      symptoms were recorded in the positive cattle, and morulae were not detected in
      the blood smears.

PMID- 19168968
TI  - An outbreak of measles classified as genotype H1 in 2008 in Osaka Prefecture.

PMID- 19168969
TI  - Genetic analysis of HA1 gene of influenza A (H3N2) viruses isolated from
      returning travelers at Chubu International Airport in Aichi Prefecture.

PMID- 19168970
TI  - Prevalence of enterovirus in Osaka, Japan, between April and September 2008.

PMID- 19168971
TI  - Genetic characterization of sporadic noroviruses in Nara Prefecture: April 2007
      March 2008.

PMID- 19168972
TI  - Isolation of oseltamivir-resistant influenza A/H1N1 virus of different origins in
      Yokohama City, Japan, during the 2007-2008 influenza season.

PMID- 19168973
TI  - A multivalent approach to drug discovery for novel antibiotics.
AB  - The design, synthesis and antibacterial activity of novel glycopeptide/beta
      lactam heterodimers is reported. Employing a multivalent approach to drug
      discovery, vancomycin and cephalosporin synthons, A and B respectively, were
      chemically linked to yield heterodimer antibiotics. These novel compounds were
      designed to inhibit Gram-positive bacterial cell wall biosynthesis by
      simultaneously targeting the principal cellular targets of both glycopeptides and
      beta-lactams. The antibiotics 8a-f displayed remarkable potency against a wide
      range of Gram-positive organisms including methicillin-resistant Staphylococcus
      aureus (MRSA). Compound 8e demonstrated excellent bactericidal activity against
      MRSA (ATCC 33591) and initial evidence supports a multivalent mechanism of action
      for this important new class of antibiotic.

PMID- 19168974
TI  - Exploring the positional attachment of glycopeptide/beta-lactam heterodimers.
AB  - Further investigations towards novel glycopeptide/beta-lactam heterodimers are
      reported. Employing a multivalent approach to drug discovery, vancomycin and
      cephalosporin synthons, 4, 2, 5 and 10, 18, 25 respectively, were chemically
      linked to yield heterodimer antibiotics. These novel compounds were designed to
      inhibit Gram-positive bacterial cell wall biosynthesis by simultaneously
      targeting the principal cellular targets of both glycopeptides and beta-lactams.
      The positional attachment of both the vancomycin and the cephalosporin central
      cores has been explored and the SAR is reported. This novel class of bifunctional
      antibiotics 28-36 all displayed remarkable potency against a wide range of Gram
      positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA).
      A subset of compounds, 29, 31 and 35 demonstrated excellent bactericidal activity
      against MRSA (ATCC 33591) and 31 and 35 also exhibited superb in vivo efficacy in
      a mouse model of MRSA infection. As a result of this work compound 35 was
      selected as a clinical candidate, TD-1792.

PMID- 19168975
TI  - Chaetomugilins, new selectively cytotoxic metabolites, produced by a marine fish
      derived Chaetomium species.
AB  - Chaetomugilins A-F have been isolated from a strain of Chaetomium globosum
      originally isolated from the marine fish Mugil cephalus, and their absolute
      stereostructures have been elucidated on the basis of spectroscopic analyses,
      including 1D and 2D NMR techniques, some chemical transformations and an X-ray
      analysis. These compounds exhibited significant growth inhibition against
      cultured P388 cells and HL-60 cells. In addition, chaetomugilins A, C and F
      showed selective cytotoxic activities against 39 human cancer cell lines.

PMID- 19168976
TI  - HS071, a new furan-type cytotoxic metabolite from Streptomyces sp. HS-HY-071.
AB  - Investigation of the bioactive metabolites from the soil-derived actinomycete,
      Streptomyces sp. HS-HY-071, a new furan-type antibiotic, HS071 (1), was isolated.
      Its structure was established as methyl 4-hydroxymethyl-2-pentylfuran-3
      carboxylate on the basis of extensive 1D and 2D NMR and MS spectral analysis. It
      exhibited in vitro activity against HCT-116 cell with an IC50 of 18.2 microg/ml.

PMID- 19168977
TI  - In vitro and in vivo antitrypanosomal activitiy of two microbial metabolites, KS
      505a and alazopeptin.
AB  - Our on-going screening program to discover new antitrypanosomal antibiotics has
      been evaluating compounds isolated from soil microorganisms as well as
      investigating the antibiotic libraries of the Kitasato Institute for Life
      Sciences and BioFrontier Laboratories of Kyowa Hakko Kogyo Co., Ltd. We have now
      discovered two compounds, KS-505a and alazopeptin, which exhibit moderate
      antitrypanosomal characteristics. We report here the in vitro and in vivo
      antitrypanosomal activities and cytotoxicities of KS-505a and alazopeptin,
      compared with some commonly-used antitrypanosomal drugs. This is the first report
      of in vitro and in vivo antitrypanosomal activities of either KS-505a or
      alazopeptin.

PMID- 19168978
TI  - Viridicatumtoxin B, a new anti-MRSA agent from Penicillium sp. FR11.
AB  - A new tetracycline-type antibiotic named viridicatumtoxin B along with the known
      compound viridicatumtoxin has been isolated from the mycelium of liquid
      fermentation cultures of Penicillium sp. FR11. The structure of viridicatumtoxin
      B was determined on the basis of MS and NMR data. Viridicatumtoxin B inhibited
      the growth of Staphylococcus aureus including methicillin-resistant S. aureus and
      quinolone-resistant S. aureus with MIC (microg/ml) of 0.5, which is similar with
      that of vancomycin, but 8-64 times higher activity than that of tetracycline.

PMID- 19168979
TI  - A two-component regulatory system involved in clavulanic acid production.
AB  - A pair of genes encoding the bacterial two-component regulatory system, orf22 and
      orf23, was found next to the clavulanic acid gene cluster of Streptomyces
      clavuligerus NRRL3585. Orf23 was deleted for the construction of S.
      clavuligerus/Deltaorf23. Although growth and morphological analyses showed no
      differences between S. clavuligerus/Deltaorf23 and wild-type, the production of
      clavulanic acid in S. clavuligerus/Deltaorf23 was found to be decreased. In
      addition, the co-overexpression of orf22/orf23 in wild-type resulted in an
      enhanced 1.49-fold production of clavulanic acid, and the complementation of
      orf22/orf23 in S. clavuligerus/Deltaorf23 restored clavulanic acid production
      about 80% as normal levels. These results demonstrate that the orf22/orf23 two
      component regulatory system participates as a positive regulator of the
      biosynthesis of clavulanic acid and increased levels of orf22/orf23 can
      contribute to enhanced production of clavulanic acid in S. clavuligerus.

PMID- 19168980
TI  - Identification of streptothricin class antibiotics in the early-stage of
      antibiotics screening by electrospray ionization mass spectrometry.
AB  - Several streptothricin antibiotics have been studied by tandem mass spectrometry.
      The dominant product ions were derived from the C(7)-N bond cleavage which lead
      to lose streptolidine from the [M+H](+). The fragmentation pathways of key ions
      were described and certained by parent scan. According to the generalized
      principles, streptothricin isomers could be distinguished easily by the
      difference of CID spectra. A facile method based on ion-pair RP-HPLC coupled with
      electrospray ionization tandem mass spectrometry has been established for the
      analysis of streptothricins in the fermentation broth of Streptomyces
      qinlingensis. A total of 19 streptothricin-like compounds were identified or
      tentatively characterized based on their mass spectral data, and in which 11 were
      the first reported compounds. This could be used as an important de-replication
      method in the programs of screening novel antibiotics.

PMID- 19168981
TI  - A new 24-membered lactone and a new polyene delta-lactone from the marine
      bacterium Bacillus marinus.
AB  - A new 24-membered macrolide macrolactin T (1), and a new polyene delta-lactone
      macrolactin U (2), along with macrolactins A, B, D, O, and S, were isolated from
      the cultured broth of the bacterium Bacillus marinus, which was isolated from
      Suaeda salsa collected in the coastline of Bohai Sea of China. The structures of
      1 and 2 were elucidated on the basis of extensive spectroscopic data analyses.
      The inhibitory activity of macrolactins T, B and D against fungi Pyricularia
      oryzae and Alternaria solani, and bacteria Staphylococcus aureus is reported.

PMID- 19168982
TI  - Mutactimycin E, a new anthracycline antibiotic with gram-positive activity.
AB  - Resistance to currently available antibiotics has become a widely recognized
      crisis in the medical community. To address this, many companies and researchers
      are refocusing their attention towards natural products, which have an excellent
      track record of producing effective antibacterial drugs. The AMRI natural product
      library was screened for activity against multi-drug resistant Staphylococcus
      aureus (MDRSA). The active samples were counter screened for cytotoxicity against
      the human hepatocellular carcinoma HepG2 cell line to determine an in vitro
      therapeutic index (in vitro TI). Those samples with a high in vitro TI were
      selected for fractionation and dereplication. This led to the discovery of a new
      anthracycline structure. This metabolite, named mutactimycin E (1), exhibited
      moderate activity against several gram positive organisms. Here we report the
      isolation, structure elucidation and biological activities of this new compound.

PMID- 19168983
TI  - A quinoline antibiotic from Rhodococcus erythropolis JCM 6824.
AB  - A new quinoline antibiotic, aurachin RE, was isolated and identified from a
      culture broth of Rhodococcus erythropolis JCM 6824. The aurachin RE structure was
      determined based on NMR and mass spectrometric analysis. The structure is similar
      to that of aurachin C antibiotics that have been identified from Stigmatella
      aurantiaca. Compared to aurachin C, however, aurachin RE exhibits a wide and
      strong antimicrobial spectrum against both high- and low-GC Gram-positive
      bacteria.

PMID- 19168984
TI  - Nataxazole, a new benzoxazole derivative with antitumor activity produced by
      Streptomyces sp. Tu 6176.
AB  - The new benzoxazole derivative nataxazole was isolated from Streptomyces sp.
      (strain Tu 6176). Nataxazole is related in structure to the potent antitumor
      compounds UK-1 and AJI9561 and showed similar strong growth inhibitory activity
      against various human tumor cell lines.

PMID- 19168985
TI  - Macrolactin S, a new antibacterial agent with FabG-inhibitory activity from
      Bacillus sp. AT28.
AB  - In the course of screening for FabG inhibitors from microbial sources, a new 24
      membered ring lactone named macrolactin S, along with the known compound
      macrolactin B, has been isolated from the mycelium of liquid fermentation
      cultures of Bacillus sp. AT28. The structure of macrolactin S was determined on
      the basis of MS and NMR data. Macrolactin S showed a dose-dependent inhibition of
      Staphylococcus aureus FabG, not inhibiting S. aureus FabI. Also macrolactin S
      inhibited the growth of S. aureus, Bacillus subtilis, and Escherichia coli.

PMID- 19168986
TI  - Chemical modification of pseurotin A: one-pot synthesis of synerazol and
      pseurotin E and determination of absolute stereochemistry of pseurotin E.
AB  - Two natural products, synerazol and pseurotin E, were synthesized from the
      natural product pseurotin A in 58% and 57% yields, respectively in one-pot
      procedures. This work also establishes the absolute stereochemistry of pseurotin
      E.

PMID- 19168987
TI  - Essential roles of Snf21, a Swi2/Snf2 family chromatin remodeler, in fission
      yeast mitosis.
AB  - ATP-dependent chromatin remodelers (ADCRs) convert local chromatin structure into
      both transcriptional active and repressive state. Recent studies have revealed
      that ADCRs play diverse regulatory roles in chromosomal events such as DNA repair
      and recombination. Here we have newly identified a fission yeast gene encoding a
      Swi2/Snf2 family ADCR. The amino acid sequence of this gene, snf21(+), implies
      that Snf21 is a fission yeast orthologue of the budding yeast Sth1, the catalytic
      core of the RSC chromatin remodeling complex. The snf21(+) gene product is a
      nuclear protein essential to cell viability: the null mutant cells stop growing
      after several rounds of cell divisions. A temperature sensitive allele of
      snf21(+), snf21-36 exhibits at non-permissive temperature (34 degrees C) a cell
      cycle arrest at G2-M phase and defects in chromosome segregation, thereby causing
      cell elongation, lack of cell growth, and death of some cell population. snf21-36
      shows thiabendazole (TBZ) sensitivity even at permissive temperature (25 degrees
      C). The TBZ sensitivity becomes severer as snf21-36 is combined with the deletion
      of a centromere-localized Mad2 spindle checkpoint protein. The cell cycle arrest
      phenotype at 34 degrees C cannot be rescued by the mad2(+) deletion, although it
      is substantially alleviated at 30 degrees C in mad2Delta. These data suggest that
      Snf21 plays an essential role in mitosis possibly functioning in centromeric
      chromatin.

PMID- 19168988
TI  - Characterization of a fission yeast P(5)-type ATPase homologue that is essential
      for Ca(2+)/Mn(2+ )homeostasis in the absence of P(2)-type ATPases.
AB  - In the fission yeast Schizosaccharomyces pombe, three P-type ATPases, namely
      Cta4p, Pmr1p, and Pmc1p, have been shown to be essential for Ca(2+) homeostasis
      and are required for specific cellular functions as well. Here, we show that the
      simultaneous deletion of pmc1(+) and SPAC29A4.19c, which encodes a putative P(5)
      type ATPase, causes a hypersensitive growth to either high concentrations of
      Ca(2+) in a medium, or the antiarrhythmic drug amiodarone, which has been known
      to cause a disruption of Ca(2+) homeostasis. On the other hand, simultaneous
      deletion of pmr1(+) and SPAC29A4.19c causes a hypersensitive growth to Mn(2+)
      depletion in a medium. The green fluorescent protein-tagged SPAC29A4.19c protein
      reveals a typical localization pattern of the Golgi proteins, but the
      SPAC29A4.19c protein is not exchangeable in function with Pmr1p, which is
      required for Ca(2+)/Mn(2+) homeostasis in secretory pathways. These results
      suggest that the putative P(5)-type ATPase encoded by SPAC29A4.19c is essential
      for Ca(2+) and Mn(2+ )homeostasis in the absence of P(2)-type ATPases, Pmc1p or
      Pmr1p, respectively. According to the precedent nomenclature of calcium/cation
      transporting ATPase in fission yeast, SPAC29A4.19 was named cta5(+) in this
      study.

PMID- 19168989
TI  - Molecular cloning and characterization of the actin-depolymerizing factor gene in
      Gossypium barbadense.
AB  - The Sea Island cotton (Gossypium barbadense L.) has been highly valued in
      verticillium wilt resistance and many fiber qualities including fiber length,
      strength and fineness. To identify whether it had some special genes in fiber
      development in comparison with the Upland cotton (G. hirsutum L.), an actin
      depolymerizing factor (ADF) gene was cloned and characterized in this research. A
      420 bp open reading frame of the cloned gene, named GbADF1, encoded a protein of
      139 amino acids, including 39.57% nonpolar amino acids, 17.27% acidic amino
      acids, 15.83% basic amino acids and 31.92% hydrophobic amino acids. Its molecular
      weight was about 15 kDa, and pI 5.04. GbADF1 contained two conserved domains, 6
      Ser and the PIP2/actin binding site. Its amino acid sequence was similar to the
      ADF/cofilin family of other plants. Compared with cDNA sequence, the GbADF1 gene
      contained one intron near the 3' end in genomic sequence. Semi-quantitative RT
      PCR result showed that GbADF1 was a constitutive expression gene in cotton, and
      higher expression level was detected in fibers than in trophic tissues. The
      GbADF1 was successfully expressed as a fusion protein in Escherichia coli BL21
      (DE3). The molecular weight was firstly calculated by SDS-PAGE. Western blotting
      analysis confirmed the existence of a protein corresponding to GbADF1. The
      structure of GbADF1 was different from that of other ADF genes in higher plant,
      although the coding sequences of all cloned ADFs were highly conserved.

PMID- 19168990
TI  - Construction of a BAC library for buckwheat genome research - an application to
      positional cloning of agriculturally valuable traits.
AB  - We have constructed a BAC library for common buckwheat Fagopyrum esculentum
      Moench. The library includes 142,005 clones with an average insert size of
      approximately 76 kb, equivalent to approximately a 7 to approximately 8-fold
      coverage of the genome. Polymerase chain reaction based screening of the library
      with AGAMOUS and FLORICAULA/LEAFY primers, has identified 7 and 9 BACs,
      respectively, which are consistent with the genome coverage. This library
      represents the first large insert genomic library for F. esculentum and it can be
      served as a genetic resource facilitating agricultural, pharmacological,
      physiological, and evolutionary studies of the species. To demonstrate the
      utilization of the library for characterizing agriculturally valuable traits, we
      developed a sequence tagged site marker tightly linked to the dwarf E locus as
      well as to the self-incompatibility complex locus and screened the library to
      initiate positional cloning of the causative genes.

PMID- 19168991
TI  - DNA polymorphism in the SUPERWOMAN1 (SPW1) locus of the wild rice Oryza rufipogon
      and its related species.
AB  - The level and pattern of nucleotide variation in the SUPERWOMAN1(SPW1) locus of
      the wild rice Oriza rufipogon and its related species were analyzed. SPW1 is
      orthologous to APETELA3(AP3) in Arabidopsis thaliana. The estimated level of
      nucleotide variation for the entire region (pi = 0.0046) was intermediate among
      those for other genes of O. rufipogon, although the estimates varied considerably
      among the SPW1 domains. Complicated haplotype structure was detected, resulting
      in a high proportion of significant linkage disequilibrium. Deviation from the
      neutrality was not detected. However, purifying selection was suggested by lack
      of replacement variation in the MADS-box and I-domain regions, which function as
      DNA-binding domain. On the other hand, an excess of drastic amino acid changes
      was detected in the C-domain, as in the AP3 region of A. thaliana. Taken
      together, these results imply that different types of natural selection are
      acting among different domains of a single protein. In the phylogenetic tree, O.
      sativa strains were included in the same cluster of O. rufipogon, supporting the
      hypothesis that O. rufipogon is the wild ancestor of O. sativa.

PMID- 19168992
TI  - Classical and molecular cytogenetic characterization of allochthonous European
      bitterling Rhodeus amarus (Cyprinidae, Acheilognathinae) from Northern Italy.
AB  - A cytogenetical study was carried out on 34 specimens of the European bitterling
      Rhodeus amarus (Teleostei: Cyprinidae, Acheilognathinae) from four rivers of the
      Venice district (NE Italy). This allochthonous fish species was accidentally
      introduced in the North-East of Italy about 20 years ago and is now rapidly
      spreading all over the rivers of the Northern part of the country. All the
      studied specimens are characterised by the same karyotype (2n = 48: 8M + 20SM +
      20ST), i.e., the typical one of the native populations of the species. However, a
      polymorphism in the number of NOR bearing chromosomes has been found. In fact, in
      addition to the main species-specific NORs, on the short arms of chromosome pair
      7, two to five additional 18S rDNA sites have been revealed by FISH in different
      specimens. Sequential staining with silver nitrate, chromomycin A(3) and DAPI
      revealed that most of the additional sites are inactive and CMA(3)-positive. Data
      herein reported confirm that in spite of an overall morphological karyological
      conservativeness, significant differences for the finer cytogenetic features can
      be found within the Acheilognathinae with the 2n = 48 and NF = 76 karyotype.

PMID- 19168993
TI  - Shorter telomere length with age in the loggerhead turtle: a new hope for live
      sea turtle age estimation.
AB  - We verified whether telomere length shortens with age in the loggerhead sea
      turtle (Caretta caretta) by measuring telomere lengths (relative telomere to
      single copy gene [T/S] ratios) in whole blood and epidermis from 20 captive
      individuals with a real-time PCR method. There was no significant correlation
      between age and relative T/S ratios in blood. Although the correlation between
      age and relative T/S ratios in epidermis was not significant, older turtles had
      smaller relative T/S ratios in epidermis. It was thus demonstrated that telomere
      length in epidermis could be a useful age estimator for sea turtles. Relative age
      information obtained with this simple, rapid, non-invasive technique may help to
      advance our understanding of the ecology of endangered sea turtles. This is the
      first publication on age-related changes in telomere length among chelonians.

PMID- 19168994
TI  - A novel role for Rad17 in homologous recombination.
AB  - Replication checkpoint protein Rad17 senses DNA lesions during DNA replication
      and halts progression of replication fork. The cells derived from Bloom syndrome
      individuals show some defects in DNA replication. In order to investigate the
      functional relationship between the replication checkpoint protein Rad17 and BLM,
      which is the product of the causative gene of Bloom syndrome, we generated
      BLM/RAD17 double knockout (blm/rad17) cells using chicken DT40 cells. The
      blm/rad17 cells showed exaggerated growth defects as determined by analysis of
      their growth curves and plating efficiency compared to those of either of the
      single gene mutants. These defects seem to be due to an increase in DNA lesions
      that cause spontaneous cell death, suggesting that Rad17 and BLM execute
      different functions in the progression of replication forks. We also demonstrate
      that targeting integration was dramatically compromised by a lack of Rad17. In
      addition, the elevated frequency of sister chromatid exchange (SCE) due to
      homologous recombination in BLM knockout (blm) cells was greatly reduced by
      disruption of the RAD17 gene. Thus, in addition to its role in the replication
      checkpoint, Rad17 appears to play a role in homologous recombination.

PMID- 19168995
TI  - Endoscopic endonasal transsphenoidal approach through the bilateral nostrils for
      pituitary adenomas.
AB  - The endoscopic endonasal transsphenoidal approach through the bilateral nostrils
      was evaluated for the treatment of pituitary adenoma. The surgical approach is
      through the bilateral nostrils via minimal or wide dissection of the septal
      mucosa, depending on the degree of tumor extension. After anterior sphenoidotomy,
      the endoscope is fixed in one nostril and required instrumentation is inserted in
      either nostril. In addition, neuronavigation and real-time hormone monitoring are
      used. Tumor removal rate, endocrinological outcomes, and complications were
      retrospectively assessed in 194 patients with pituitary adenomas who underwent
      213 procedures between December 2001 and March 2008. Greater than 95% resection
      was achieved in 74 of 131 nonfunctioning adenomas, and the removal rate was
      significantly higher during 2005-2008 compared to 2002-2004 (p < 0.05).
      Endocrinological remission was achieved in 20 of 26 growth hormone-secreting
      tumors of Knosp grades 0-2, 16 of 17 microprolactinomas, and 6 of 9 cases of pure
      Cushing's disease. Postoperative complications were cerebrospinal fluid leakage
      in 9 cases, visual worsening in 5, anterior pituitary insufficiency in 5, and
      permanent diabetes insipidus in 2. The bilateral endonasal approach provides a
      wide working area without the need for special instrumentation. By modifying
      mucosal dissection, the endoscopic approach provides flexibility and less
      invasiveness. The use of neuronavigation or intraoperative hormone monitoring
      leads to improved surgical results. The present study confirms that this approach
      is suitable for more extensive sellar tumors.

PMID- 19168996
TI  - Early appearance of high grade glioma on magnetic resonance imaging.
AB  - The early appearance of high grade glioma on magnetic resonance (MR) imaging was
      retrospectively reviewed in the clinical records and MR images of 52 patients
      with intracerebral glioma treated in Osaka General Medical Center between 1997
      and 2006. Three patients had no abnormal findings, and four patients had only
      hyperintense areas on T(2)-weighted imaging at initial MR examination. Five of
      the seven patients presented with generalized seizures. Six of the seven patients
      developed tumor progression within only 5 months. All patients underwent surgical
      tumor resection and the histological diagnoses were all high grade gliomas,
      glioblastomas in five, gliosarcoma in one, and anaplastic astrocytoma in one.
      Surveillance MR imaging should be performed at short intervals in adult patients
      presenting with seizures but with no or minimal abnormalities on initial MR
      imaging to identify progression of high grade glioma at the earliest opportunity.

PMID- 19168997
TI  - Preliminary measurement of intraoperative sympathetic nerve activity using
      microneurography and laser Doppler flowmetry during surgical resection of
      suprasellar tumors.
AB  - Intraoperative microneurography (enabling direct measurement of sympathetic
      outflow) and laser Doppler flowmetry were used to measure skin sympathetic nerve
      activity (SSNA) and skin blood flow (SBF) as indicators of hypothalamic damage
      during resection of 12 suprasellar tumors, 6 craniopharyngiomas, 4 meningiomas, 1
      pituitary adenoma, and 1 germ cell tumor. SSNA was measured from a tungsten
      microelectrode inserted into the peroneal nerve, and SBF was measured from the
      foot innervated by the peroneal nerve. SBF reduction was induced by nociceptive
      procedures and non-nociceptive procedures before tumor exposure, on exposed
      tumors, and directly on the hypothalamus. SSNA could be reliably recorded in only
      4 patients because of technical difficulties. In these patients, SSNA bursts
      appeared, followed by SBF reduction. The number of SSNA bursts was 37% to 100% of
      the number of SBF reduction events. Various surgical procedures involving painful
      stimuli or mechanical stress on the hypothalamus induced SSNA bursts and SBF
      reduction. The present findings suggest that SSNA and SBF can be used to detect
      sympathetic nerve activity, as an indicator of hypothalamic function, during
      neurosurgical procedures.

PMID- 19168998
TI  - Timing of craniotomy in a patient with multiple trauma including head injury.
AB  - A 7-year-old boy suffered blunt multiple injuries to the head, face, chest, and
      abdomen in a motor vehicle accident. On admission he had impaired consciousness
      and dyspnea. Radiographic studies revealed facial fracture and pulmonary
      contusion. Shortly after admission, he fell into shock due to intraabdominal
      bleeding. Laparotomy revealed spleen rupture. His vital signs remained unstable
      and bloody drainage from the abdominal cavity continued after surgery. Computed
      tomography showed traumatic intracerebral hematoma in the right temporal lobe,
      enlarging and compressing the brainstem. Abdominal reoperation was performed
      first to control the bleeding and stabilize the hemodynamics, disclosing renal
      laceration. Then evacuation of the intracerebral hematoma and decompressive
      craniectomy was performed. Postoperatively, his hemodynamics were stabilized.
      Clinical course was uneventful and neurological deficits gradually improved.
      Three months after the trauma, the patient was discharged on foot. This case
      emphasizes the importance of hemodynamic stability in decisions of neurosurgical
      indication and timing in patients with multiple trauma including head injury.

PMID- 19168999
TI  - Hemispheric laminar necrosis as a complication of traumatic carotid-cavernous
      sinus fistula.
AB  - A 43-year-old woman presented with a very rare case of hemispheric laminar
      necrosis as a complication of traumatic carotid-cavernous sinus fistula (CCF).
      The patient suffered head injury and extensive burns following a car accident.
      Oral intubation was performed under sedation. When sedation was discontinued 17
      days after injury, the patient demonstrated left hemiparesis. Magnetic resonance
      imaging showed laminar necrosis affecting the right cerebral hemisphere.
      Angiography revealed a right high-flow direct CCF. Transarterial embolization of
      the fistula using a detachable balloon achieved complete occlusion of the
      fistula. However, the left hemiparesis persisted following this intervention.
      Traumatic CCF may be missed in patients with disturbed consciousness, so
      clinicians should not overlook possibility of the triad of symptoms of CCF in
      patients with head injury.

PMID- 19169000
TI  - Ruptured tectal arteriovenous malformation demonstrated angiographically after
      removal of an unruptured occipital lobe arteriovenous malformation.
AB  - We report a case of ruptured tectal arteriovenous malformation (AVM) that was
      demonstrated angiographically only after removal of an unruptured occipital AVM.
      A 57-year-old man presented with sudden onset of diplopia and tinnitus. Computed
      tomography revealed a small hemorrhage in the right tectum mesencephali with
      intraventricular hemorrhage. Magnetic resonance imaging and angiography disclosed
      AVM in the right occipital lobe which was separate from the hemorrhagic lesion.
      Angiography demonstrated that the right occipital AVM was fed by the parieto
      occipital artery and drained into the superior sagittal sinus and vein of Galen.
      However, no abnormal vascular lesion was detected near the tectum mesencephali.
      As venous hypertension was considered the reason for hemorrhage, the occipital
      AVM was completely resected. Postoperative angiography demonstrated disappearance
      of the occipital AVM, but it also disclosed a small tectal AVM fed by branches
      from the superior cerebellar artery, which had not been detected on preoperative
      angiography. This was considered the true cause of hemorrhage, and gamma knife
      surgery was accordingly performed. Even if an AVM is demonstrated, if the lesion
      does not correspond to the hemorrhage we recommend serial angiographical
      evaluation so that a small AVM is not missed.

PMID- 19169001
TI  - Intracerebral hemorrhage caused by a neoplastic aneurysm from pleomorphic lung
      carcinoma.
AB  - A 61-year-old man presented with an extremely rare neoplastic cerebral aneurysm
      caused by brain metastasis from pleomorphic lung carcinoma manifesting as
      intracerebral hematoma and sudden onset of semicoma. Computed tomography
      demonstrated huge intracerebral hemorrhage in the left cerebral hemisphere, which
      had collapsed into the lateral ventricle. Cerebral angiography disclosed a
      fusiform aneurysm in the periphery of the left middle cerebral artery
      (approximately 2 mm diameter). Resection of the aneurysm and removal of the
      hematoma were performed. Histological examination revealed that the aneurysm
      walls were invaded by pleomorphic carcinoma. The present case indicates that
      neoplastic cerebral aneurysm may be the cause of intracerebral hemorrhage in
      patients with pleomorphic lung carcinoma.

PMID- 19169002
TI  - Osteochondroma of the sella turcica presenting with intratumoral hemorrhage.
AB  - A 29-year-old man presented with a primary sellar turcica osteochondroma
      manifesting as intratumoral hemorrhage mimicking pituitary apoplexy. The patient
      suffered sudden onset of headache concomitant with vision loss in the left eye.
      Radiography and computed tomography detected destruction and calcification of the
      sellar turcica. Magnetic resonance imaging revealed a heterogeneously enhanced
      suprasellar mass that had elevated and compressed the optic chiasm. The
      preoperative diagnosis was hemorrhagic pituitary adenoma, craniopharyngioma,
      meningioma, or chordoma based on the signal heterogeneity of the lesion. To
      relieve the symptoms and make a definitive diagnosis, surgical removal via a
      basal interhemispheric approach was carried out. The tumor was not totally
      removed because of tight adhesion to the pituitary stalk, but postoperative
      ophthalmological examination revealed improvement of the visual disturbance. The
      histological diagnosis was osteochondroma based on the presence of mature
      chondrocytes and osteomatous tissue. Osteochondroma should be included in the
      differential diagnosis of tumors with acute hemorrhage in the sella turcica.

PMID- 19169003
TI  - Choice of posterior subtemporal transtentorial approach for tumor resection in
      deep anteromedial superior cerebellum.
AB  - The anteromedial superior cerebellar tumor can be accessed by various routes. For
      tumor presenting at the cerebellar surface in this region, the optimal approach
      remains contentious. Furthermore, which of the various routes offers the optimal
      approach to a tumor that is not present at the cerebellar surface but lies deep
      anteromedial superior cerebellum is a matter of debate. We report herein the case
      of a 44-year-old woman with hemangioblastoma deep within the subcortex of the
      anteromedial superior cerebellum. Preoperative magnetic resonance (MR) imaging
      and three-dimensional anisotropy contrast MR axonography using diffusion-weighted
      MR imaging demonstrated that the posterior subtemporal transtentorial (PSTT)
      approach would provide a shorter surgical corridor, minimal cerebellar split, and
      better preservation of nerve fibers, compared to the other approaches. Surgical
      tumor removal was successfully achieved using the PSTT approach. During surgery,
      the PSTT approach provided an operative field that enabled visualization of the
      proximal side of the superior cerebellar artery as the tumor feeding vessel.
      Although the vein of Labbe inserted just into the transverse-sigmoid junction,
      injury to this vein was avoided using optimal head position, cerebrospinal fluid
      drainage, and various devices. For patients with tumor located within the
      subcortex of the anteromedial superior cerebellum, the PSTT approach is
      recommended as an optimal surgical route. Scrupulous evaluation using
      preoperative neuroimaging is crucial when deciding on the surgical approach.

PMID- 19169004
TI  - Coexistence of Chiari 2 malformation and moyamoya syndrome in a 17-year-old girl.
AB  - A 17-year-old female with Chiari 2 malformation developed cerebral infarction
      with angiographically typical bilateral moyamoya vessels manifesting as sudden
      onset of moderate left hemiparesis. Magnetic resonance imaging revealed multiple
      infarcts in the right frontal lobe, agenesis of the corpus callosum, upward
      herniation of the dorsal cerebellum, tectal beak of the midbrain, and downward
      herniation of the cerebellar vermis. Cerebral angiography demonstrated occlusion
      of the bilateral internal carotid arteries and basal moyamoya vessels. Single
      photon emission computed tomography showed significantly reduced regional
      cerebral blood flow in the right frontoparietal cortex. The cerebral vascular
      reactivity to acetazolamide was diminished in both cerebral hemispheres. She
      underwent superficial temporal artery-middle cerebral artery anastomosis combined
      with encephalo-myo-synangiosis on the right, and on the left 6 months later.
      Cerebral angiography performed 4 months after the second operation showed good
      patency of the bypasses and substantial collateral vessels in both cerebral
      hemispheres. This association may have happened by chance, and a common etiology
      is uncertain, but a currently undetermined genomic component might have
      contributed to the disease progression.

PMID- 19169005
TI  - Trends in kidney donation among kidney stone formers: a survey of US transplant
      centers.
AB  - BACKGROUND: Living kidney donation is on the rise and acceptance criteria for
      potential donors are evolving to include more 'complex' patients such as kidney
      stone formers. Transplant centers are faced with sparse data on patient outcomes
      when evaluating potential donors who are stone formers; thus, attitudes and
      practice can differ greatly between centers. METHODS: We conducted a survey of
      United States kidney transplant programs to assess current trends in the approach
      to dealing with stone formers who are evaluated for kidney donation. RESULTS:
      Based on the survey results, there appears to be a tendency toward increased
      acceptance of donors with a history of kidney stones. 77% of responding centers
      allowed stone formers to donate. Nearly 40% of centers reported that their
      attitude towards accepting donors with kidney stones has changed over the last 5
      10 years. Among these, the overwhelming majority reported that they were more
      likely to accept these donors. CONCLUSIONS: Such trends are likely based on organ
      need, as published patient outcomes and evidence-based guidelines are lacking for
      this unique group of patients. We propose the need for a study to formally
      evaluate the outcome of stone formers who donate a kidney in order to
      systematically examine whether appropriately selected stone formers can safely
      donate.

PMID- 19169006
TI  - Recent therapeutic strategies improve renal outcome in patients with IgA
      nephropathy.
AB  - BACKGROUND/AIMS: Various treatment options for IgA nephropathy (IgAN) have been
      developed, particularly over the past decade. Nevertheless, whether such
      therapeutic interventions improve actual renal outcome as compared with previous
      therapies remains obscure. METHODS: We examined data from 304 patients with IgAN
      whose serum creatinine value at renal biopsy was <2.0 mg/dl and who had been
      followed up for >12 months. We assigned the patients to groups according to the
      period of diagnosis (group E, between 1981 and 1995, n = 130; group L, between
      1996 and 2006, n = 174). RESULTS: Significantly more patients had received
      steroid therapy and renin-angiotensin system inhibitors (RAS-I) in group L than
      in group E (steroid 51.7 vs. 15.4%, p < 0.001; RAS-I 42.0 vs. 1.5%, p < 0.001).
      Forty patients overall reached end-stage renal disease (ESRD) within 81.9 +/-
      55.1 months of observation. Kaplan-Meier analysis showed that the 10-year renal
      survival rate of group L persisted and significantly differed from that of group
      E (95.7 vs. 75.2%, p = 0.005). The Cox proportional hazards model adjusted for
      known prognostic markers demonstrated that initial therapeutic interventions in
      group L prevented ESRD, with a hazard ratio of 0.29 (95% CI 0.11-0.76, p =
      0.011). CONCLUSION: Although this study is not a prospective trial, our results
      indicate that aggressive therapeutic intervention for IgAN over the past decade
      has improved actual renal outcome.

PMID- 19169007
TI  - Protective effect of fish consumption on colorectal cancer risk. Hospital-based
      case-control study in Eastern Europe.
AB  - BACKGROUND/AIMS: Current epidemiologic studies investigating the effect of fish
      intake on colorectal cancer (CRC) risk are scarce. Therefore, the aim of this
      study was to elucidate the relationship between fish consumption and CRC risk.
      METHODS: This hospital-based case-control study was performed in 548 CRC patients
      (Surgery Clinic, University Hospital in Krakow, Poland) between November 2000 and
      May 2008. Histological findings, information on anatomic location and stage of
      cancer were available for all the patients enrolled in this study. The control
      group consisted of 745 patients of the same hospital with no history of cancer
      admitted for treatment of non-neoplastic conditions. During the 5-year study
      period, the food frequency questionnaire used focused on the reference period
      that was defined as 1-5 years prior to CRC diagnosis for the CRC cases and the
      date of hospital admission for the controls. RESULTS: The crude odds ratio (OR)
      was inversely related to fish consumption (z for trend in quartiles of intake= 
      2.31, p=0.021; OR=0.89; 95% confidence interval, CI: 0.81-0.98). The risk of CRC
      increased with intake of stewed or cooked meat (z for trend in quartiles of
      intake=2.14; p=0.032; OR=1.11; 95% CI: 1.01-1.23). The adjusted OR showed a
      significant reduction in CRC already at the moderate fish intake of one or two
      servings per week (OR=0.70; 95% CI: 0.51-0.94), but it was even lower at higher
      fish intake (OR=0.56; 95% CI: 0.39-0.86). All multivariate statistical models
      employed in the analysis considered potential confounders, such as demographic
      characteristics of subjects, body mass index, smoking status, leisure time
      physical activity, energy consumption and intake of meat products. CONCLUSIONS:
      The study results indicate that increased fish intake may have a preventive
      effect on CRC and modulate the effect of meat consumption. To our knowledge, this
      is the first large epidemiologic study on dietary habits and CRC incidence in
      Eastern Europe.

PMID- 19169008
TI  - PAX6 immunoreactivity in the diencephalon and midbrain of alligator during early
      development.
AB  - PAX6 expression was examined during early development of the diencephalon and
      midbrain of Alligator using an immunocytochemical methodology. These observations
      focused on the basal plate to determine whether diencephalic prosomere
      organization in this region followed a pattern previously identified for alar
      plate areas. PAX6 expression was also described in alar diencephalic regions and
      the adjacent midbrain. PAX6 (+) cells in the basal plate were first seen in
      prosomere 1 at stage 7, in the midbrain at stage 10, and lastly in prosomeres 2
      and 3 at stage 11. By stage 12, a nearly continuous column of PAX6 (+) cells
      extended from the midbrain basal plate through the entire diencephalon. In the
      diencephalon, PAX6 (+) cells in the basal plate were of greatest number in
      prosomere 1, least in prosomere 2, and intermediate in prosomere 3. This pattern
      of PAX6 expression distinguished these individual basal plate prosomeres. These
      results indicate that basal plate prosomeres follow a pattern similar to alar
      plate prosomereric organization during the later stages of early diencephalon
      development. Over a comparable time period of early diencephalon development,
      similar observations have been made in chick basal plate. In Alligator and chick,
      PAX6 expression in the basal plate is similar in the midbrain and prosomere 1 but
      different in prosomeres 2 and 3: present in Alligator and absent in chick. In
      alar plate areas of the Alligator diencephalon, PAX6 expression follows a similar
      pattern to that described for chick and mouse. These similarities in PAX6
      expression in alar diencephalic prosomeres suggest that this is a common feature
      of amniotes. Differential PAX6 expression in alar prosomere 1 and the midbrain in
      Alligator is similar to that described for a wide range of species which suggests
      that these features are common to all vertebrates.

PMID- 19169009
TI  - RRI's 11th International Conference on Dialysis, Advances in CKD 2009, emphasizes
      new developments in both technology and process.

PMID- 19169010
TI  - Improvements in technology: a path to safer and more effective hemodialysis.
AB  - Effective dialysis therapy is now understood to encompass both small and large
      solute removal, using approaches that minimize intradialytic symptoms and
      maximize patient safety. Achieving the goal of providing effective dialysis for
      an expanding population of patients with increasingly complex medical problems at
      a time of limited resources will require technological innovation. To address
      this need, the latest generation of ergonomically designed dialysis machines
      incorporates as standard features the technology required to perform on-line
      convective therapies to maximize large solute removal, on-line measurement of
      ionic clearance to monitor small solute removal and real-time data processing to
      guide the delivery of therapy. In addition, these machines feature feedback
      control systems that may help reduce the unpleasant side effects associated with
      fluid removal during hemodialysis. These technological innovations offer
      therapeutic versatility while, at the same time, reducing the burden on patient
      care personnel, and are likely to make an important contribution to delivering
      safer and more effective dialysis therapy.

PMID- 19169011
TI  - How do changes in water quality and dialysate composition affect clinical
      outcomes?
AB  - Dialysis relies upon the transfer of waste products and electrolytes across a
      semi-permeable membrane contained in the dialyser facilitated by the dialysis
      fluid, a fast-flowing electrolyte solution prepared continuously by the mixing of
      treated water with a concentrated electrolyte solution. Both the water, the
      buffer and electrolyte composition play important roles in modulating
      complications associated with treatment. With respect to water, historically the
      focus was on chemical contaminant content, but more recently has shifted to
      microbiological quality due to the role that such quality plays in the pro
      inflammatory state. The composition of the dialysis fluid is crucial in
      normalization of electrolyte composition of plasma water, homeostasis and acid
      base balance, and should be individualized to the patients' requirements in the
      same way as blood and dialysate flow rates are individualized to ensure optimal
      comfort and minimal complications associated with the procedure.

PMID- 19169012
TI  - The medical directorship of renal dialysis facilities under the new Medicare
      conditions for coverage: challenges and opportunities.
AB  - The new Medicare conditions for coverage for providers of end-stage renal disease
      services provide both a challenge and an opportunity for medical directors. The
      conditions expect active clinical leadership in quality improvement and the
      performance of the facility staff and medical staff. These new rules define
      patient assessment and care planning processes that complement the quality
      assessment and performance improvement (QAPI) program. Infection control, patient
      safety and error reduction are given new emphasis. The interdisciplinary team
      (IDT) under the leadership of the medical director will advance the quality and
      safety of the patients under their care. Patients' rights and autonomy are
      stressed. The QAPI/IDT will monitor complaints, satisfaction surveys, and
      grievances to minimize involuntary discharge. The medical director will report
      the results of the QAPI program to the governing body. Medical directors will
      find that participation in renal network quality improvement programs and
      initiatives will enhance their facility's QAPI program.

PMID- 19169013
TI  - Vascular access: the past, present and future.
AB  - Over the past 40 years, improvements in vascular access management have enhanced
      patient outcomes and decreased an epidemic of access failure. Arteriovenous
      fistulae are again the access of choice and new percutaneous therapies and
      outpatient access centers have revolutionized the therapeutic approach to access
      failure. Evidence-based guidelines, supported by national and international
      outcome data have helped rationalize vascular access care. Current challenges
      and, in particular, the increased use of catheters with resultant increases in
      patient morbidity and mortality must be rapidly addressed to protect patients and
      decrease the unacceptably high rates of catheter-related infection. Future
      technologies will continue to improve vascular access management. Our ability to
      utilize these new approaches to benefit patients will depend on appropriate
      application, continued development of standardized delivery systems utilizing
      outcome measures and payment systems that support and incent outcome improvement.

PMID- 19169014
TI  - Role of vasopressin and vasopressin receptor antagonists in type I cardiorenal
      syndrome.
AB  - The pathogenesis of cardiac failure involves activation of the neurohumoral axis
      including stimulation of the sympathetic nervous system, the renin-angiotensin
      aldosterone, and nonosmotic vasopressin systems. While these responses are
      critical in maintaining arterial pressure, they are associated with renal
      vasoconstriction, as well as sodium and water retention. In advanced
      circumstances, renal dysfunction and hyponatremia occur with cardiac failure.
      Even a modest rise in serum creatinine related to diminished renal function in
      heart failure patients is associated with increased risk for cardiovascular
      morbidity and mortality. Similarly, increased thirst and the nonosmotic
      stimulation of vasopressin in advanced cardiac failure leads to hyponatremia,
      which is also a major risk factor for mortality. Currently, V2 vasopressin
      receptor antagonists have been shown to correct hyponatremia in cardiac failure.
      One such agent, conivaptan, also is a V1 receptor antagonist which could
      theoretically benefit heart failure patients by decreasing cardiac afterload and
      remodeling. The effect of V2 receptor antagonists to correct hyponatremia in
      heart failure patients appears to be quite safe. However, to date no effect on
      mortality has been demonstrated.

PMID- 19169015
TI  - Validity of internal filtration-enhanced hemodialysis as a new hemodiafiltration
      therapy.
AB  - In order to improve solute removal efficiency, several types of dialyzers with
      enhanced internal filtration (IF) were introduced for clinical applications. In
      these dialyzers, enhanced IF increased convective transport of the solute in
      addition to diffusive transport. Internal filtration-enhanced hemodialysis
      (IFEHD) defined as hemodialysis therapy using the enhanced IF dialyzer seems to
      be more convenient in comparison with conventional hemodiafiltration therapies
      because of no additional equipments such as a roller pump. In this paper, the
      validity of IFEHD was examined during several types of experimental studies. As a
      result, the experimental study with several types of enhanced IF dialyzers
      indicated values of relative solute clearance in an aqueous solution that were
      higher than unity compared to the conventional dialyzer. The K values obtained
      for myoglobin as a larger molecule were more than twice as high. The value of IF
      flow rate (Q(IF)) was evaluated by pulsed Doppler ultrasonography. The blood flow
      velocity at a cross-sectional plane of the dialyzer was directly measured along
      the dialyzer during a bovine in vitro study using a newly developed probe slider.
      Doppler ultrasonography is a useful method as a bedside monitoring of the Q(IF)
      value in a dialyzer because it is noninvasive for the patient. Time course of the
      Q(IF) value was examined for 6 h during a bovine in vitro study. The Q(IF)
      decreased within 45 min after the start of the experiment and reached constant
      values after that. Although creatinine and beta(2)-microglobulin K values
      remained constant with time during the experiment, alpha(1)-microglobulin K
      values gradually and albumin K value steeply decreased with time. This is because
      these solutes transfer through the membrane strongly affected by fouling. The
      validity of IFEHD was clarified during the experimental studies. Development of a
      dialyzer with enhanced IF, however, should take account of the patient's safety.
      Contaminations such as endotoxin invasion from the dialysate to the patient
      should be avoided.

PMID- 19169016
TI  - Temporal evolution of clinical parameters before death in dialysis patients: a
      new concept.
AB  - BACKGROUND: Chronic hemodialysis (HD) patients experience an appallingly high
      mortality in the range of 20% per year. Little is known on the dynamics of key
      clinical and laboratory variables in the weeks and months preceding death. In
      order to gain more insight into events preceding death, we embarked on a novel
      methodological approach which encompasses data analysis from the date of death
      backwards in time. METHODS: The current study investigates the dynamics of
      postdialytic weight and serum albumin levels in the 24 months preceding death. We
      performed a retrospective analysis of 2,462 maintenance HD patients who died
      between July 1, 2005 and April 30, 2008. Patients' monthly serum albumin levels
      were extracted for the 24 months preceding the date of death. Similarly, the
      median weekly postdialysis weight was extracted for the 104 weeks prior to death.
      Data were analyzed with linear mixed models. RESULTS: Both albumin levels and
      postdialytic body weight showed a significant decrease irrespective of gender and
      race in the 3 final months of life. The most pronounced decreases in postdialytic
      weight and albumin levels were observed in patients with infection as cause of
      death, the smallest changes occurred in subjects with cerebrovascular events.
      CONCLUSIONS: In their final 3 months of life, HD patients experience a marked
      decrease in body weight and serum albumin levels. A better understanding of
      dynamic patterns of key variables before death may be useful in developing
      processes which alert medical caregivers to patients at increased risk, in order
      to institute timely diagnostic and therapeutic interventions.

PMID- 19169017
TI  - Prenatal causes of kidney disease.
AB  - It has recently been increasingly recognised that disturbed intra-uterine
      development may impact on renal and cardiovascular risk in adult life, e.g.
      albuminuria and chronic kidney disease, hypertension, type 2 diabetes or
      cardiovascular events. According to Barker's hypothesis, when resources in utero
      are restricted, their allocation to the development of the kidney and pancreatic
      islets is restricted to guarantee appropriate development of the brain and heart.
      The underlying epigenetic mechanisms involve modification of gene expression by
      altered DNA methylation and histone acetylation as well as by allocation of stem
      cells. The result of this trade-off between the brain and kidney during
      organogenesis is a diminished number of nephrons ('nephron underdosing') which
      predisposes to albuminuria and risk of chronic kidney disease, as well as
      hypertension. In parallel, changed appetite centres, insulin resistance and beta
      cell development predispose to obesity, metabolic syndrome and type 2 diabetes
      and the resulting renal sequelae. Numerous factors may trigger intra-uterine
      restriction of fetal growth, such as uterine underperfusion, maternal
      malnutrition, hyperglycaemia and hyperinsulinaemia of the mother, smoking or
      medications.

PMID- 19169018
TI  - Reassessing marketing of kidneys from the 2008 perspective.
AB  - Progressive improvements in all aspects of the kidney transplant regimen
      establish this form of renal replacement therapy as superior to peritoneal or
      hemodialysis in terms of extent of rehabilitation and long-term recipient
      survival. Continuous growth in the number of patients with kidney failure
      sustained by dialytic therapy has not been associated with substantially
      increased deceased donor kidney contributions, causing intensified stressful
      waiting periods for potential recipients lacking a live kidney donor. Neither
      public relation campaigns nor local government efforts have substantially
      increased kidney donation. Buying a donor kidney is illegal and condemned as
      fostering exploitation of poor people by the wealthy. Widely publicized examples
      of coercion of unwilling donors create a negative image of harmful, inhumane
      conduct deployed to obtain kidneys sold and transplanted under unsavory
      circumstances. Yet efforts to establish and test governmental programs to
      supervise and sustain acceptable standards for the sale and implantation of
      kidneys from fully informed, medically evaluated and protected, fairly
      compensated donors have been resisted and frustrated by those who consider such
      compensation loathsome. Accordingly, while selling kidneys is prohibited by law,
      pressure from those wanting to quench the number of deaths of wait-listed
      dialysis patients continues forcing reexamination of an issue that, like
      prohibition of the possession and sale of alcohol in the United States in 1920,
      places the will of a people in opposition to unreasonably restrictive laws. The
      debate continues.

PMID- 19169019
TI  - Enhancing hemodialysis efficacy through neuromuscular stimulation.
AB  - Beat-to-beat blood pressure monitoring was used to assess the efficacy of reflex
      mediated, calf muscle pump stimulation to enhance cardiovascular refilling in
      subjects in the supine and seated positions, with extension of this stimulation
      technology to dialysis evaluated in 2 dialysis patients. Micromechanical
      stimulation (50 mum at 45 Hz) of the plantar surface was found to significantly
      increase both the rate and volume of cardiovascular refilling relative to that
      observed for subjects in the supine position. During hemodialysis, calf muscle
      pump stimulation permitted significantly increased ultrafiltrate removal,
      specifically from 78 to 96% of clinical goal, while serving to maintain both
      blood pressure and blood volume.

PMID- 19169020
TI  - Reduction of hepatitis C virus using lectin affinity plasmapheresis in dialysis
      patients.
AB  - BACKGROUND/AIMS: To test the safety and efficacy of the Aethlon Hemopurifier, a
      lectin affinity cartridge, in clearing hepatitis C virus (HCV) from the blood of
      HCV-positive end-stage renal disease patients undergoing dialysis. Viral RNA was
      measured using real-time quantitative reverse transcriptase polymerase chain
      reaction. RESULTS: HCV clearance from plasma or blood was measured using either
      direct capture on immobilized Galanthus nivalis agglutinin (GNA) or using
      miniature plasmapheresis cartridges containing immobilized GNA. HCV in plasma
      samples was rapidly cleared by direct affinity capture (t(1/2) = approx. 20 min)
      and HCV in human blood was cleared using the Hemopurifier (t(1/2) = 2-3 h).
      Institutional-review-board-sanctioned clinical safety studies were conducted at
      the Apollo and Fortis Hospitals in India. At Apollo, 4 patients were treated 3
      times/week for 2 weeks. HCV captured on the Hemopurifier averaged 8.9 x 10(8)
      viral copies/cartridge (n = 5), representing approximately 30% of the initial
      viral body burden. At Fortis, 3 patients treated 3 times/week for 1 week
      completed the viral load studies. Two patients showed measurable viral load
      reduction, while the third showed both increases and decreases in viral load.
      After Hemopurifier treatment, average HCV viral load was reduced by 57%.
      Surprisingly, average viral load was also 82% lower 7 days after treatment.
      Control samples also showed a marked transient reduction in HCV viral load as
      previously reported. CONCLUSION: The Hemopurifier rapidly cleared HCV from blood
      treated in vitro. In patients, the combination of the Hemopurifier plus dialysis
      decreased HCV viral load by 57% in 1 week. Moreover, viral load reduction
      continued up to 7 days after treatment.

PMID- 19169021
TI  - Bioimpedance analysis in dialysis: state of the art and what we can expect.
AB  - Dialysis must control the body's fluid content accurately in order to maintain
      optimal health. The only commonly used, practical and objective measurements we
      have to guide fluid removal are very inaccurate. Recent study has validated
      bioimpedance (BIA) as an objective measure of fluid and nutritional status in
      dialysis patients. There are a number of different methods suitable for routine
      use available to the clinician. Single-frequency whole-body BIA uses inexpensive
      equipment capable of almost instantaneous or continuous measurement. The results
      can be used to give an indication of a patient's fluid content, nutrition and
      body composition when compared to appropriate reference values. Multiple
      frequency whole-body BIA can be used to calculate excess fluid volume to within 1
      2 liters. The equipment is more expensive than for single-frequency BIA, but the
      output is much easier to interpret. Multiple-frequency segmental BIA is more
      complicated to perform, but subject to less interference from changes in fluid
      distribution (e.g. resulting from hemodialysis or changes in posture). It is not
      suitable for routine use but could be considered as a gold standard for
      occasional clinical BIA.

PMID- 19169022
TI  - Importance of whole-body bioimpedance spectroscopy for the management of fluid
      balance.
AB  - INTRODUCTION: Achieving normohydration remains a non-trivial issue in
      haemodialysis therapy. Preventing the deleterious effects of fluid overload and
      dehydration is difficult to achieve. Objective and clinically applicable methods
      for the determination of a target representing normohydration are needed.
      METHODS: Whole-body bioimpedance spectroscopy (50 frequencies, 5-1,000 kHz) in
      combination with a physiologic tissue model can provide an objective target for
      normohydration based on the concept of excess extracellular volume. We review the
      efficacy of this approach in a number of recent clinical applications. The
      accuracy to determine fluid volumes (e.g. extracellular water), body composition
      (e.g. fat mass) and fluid overload was evaluated in more than 1,000 healthy
      individuals and patients against available gold standard reference methods (e.g.
      bromide, deuterium, dual-energy X-ray absorptiometry, air displacement
      plethysmography, clinical assessment). RESULTS: The comparison with gold standard
      methods showed excellent accordance [e.g. R(2) (total body water) = 0.88; median
      +/- SD (total body water) = -0.17 +/- 2.7 litres]. Agreement with high-quality
      clinical assessment of fluid status was demonstrated in several hundred patients
      (median +/- SD = -0.23 +/- 1.5 litres). The association between ultrafiltration
      volume and change in fluid overload was reflected well by the method (median +/-
      SD = 0.015 +/- 0.8 litres). The predictive value of fluid overload on mortality
      underlines forcefully the clinical relevance of the normohydration target, being
      secondary only to the presence of diabetes. The objective normohydration target
      could be achieved in prevalent haemodialysis patients leading to an improvement
      in hypertension and reduction of adverse events. CONCLUSION: Whole-body
      bioimpedance spectroscopy in combination with a physiologic tissue model provides
      for the first time an objective and relevant target for clinical dry weight
      assessment.

PMID- 19169024
TI  - New insights into lipid metabolism in chronic kidney disease: what are the
      practical implications?
AB  - The risk of cardiovascular disease increases with declining glomerular filtration
      rate. Hyperlipidemia and dyslipidemia, characterized by increased triglycerides
      and low levels of high-density lipoprotein, are both associated with
      cardiovascular outcome as well as the risk of progression of loss of renal
      function. Both hyperlipidemia and dyslipidemia respond to pharmacologic therapy,
      including hydroxymethylglutaryl-CoA reductase inhibitors and fibric acid
      derivatives, to alteration in diet as well as to extreme measures such as
      bariatric surgery. However, the effects of these modalities on cardiovascular or
      renal outcomes are dependent upon the level of renal function. There is strong
      evidence that patients with stages 1-3 chronic kidney disease attain benefit from
      lipid-lowering therapy both with reduction in cardiovascular risk and possibly
      reduction in the rate of decline in renal function. Among dialysis patients
      little risk reduction appears to be achieved by treatment of low-density
      lipoprotein cholesterol level. Bariatric surgery reduces hyperlipidemia in
      patients with chronic kidney disease, but has also been associated with
      subsequent rapid decline in renal function secondary to oxalate deposition.

PMID- 19169023
TI  - Bacterial DNA in water and dialysate: detection and significance for patient
      outcomes.
AB  - The fluid used for hemodialysis may contain DNA fragments from bacteria, which
      could be harmful for patient outcomes. DNA fragments from bacteria, containing
      the nonmethylated CpG motif, can trigger inflammation through the monocyte and
      lymphocyte Toll-like receptor 9, and these DNA fragments have been observed in
      dialysate. The fragments may transfer across the dialyzer into the patient's
      bloodstream during hemodialysis treatment. During hemodiafiltration, the
      fragments would be introduced directly into the bloodstream. The DNA fragments
      may arise from biofilm in the pipes of the water system, from growth of bacteria
      in the water, or as contaminants in the bicarbonate and salt mixture used for
      preparation of dialysate. Current filtration methods, such as Diasafe filters,
      are not able to remove these fragments. It would be prudent to seek to reduce or
      eliminate these contaminants. However, the cost and effort of decreasing
      bacterial DNA content may ultimately require substantial facility improvements;
      we therefore need to fund research studies to determine if modifications to
      reduce bacterial DNA content are clinically warranted. This research will require
      methods to accurately determine the species of bacteria that contribute the DNA,
      since this information will allow the source to be established as biofilm,
      bicarbonate mixtures, or other problems in the dialysis system such as bacterial
      growth or leakage during water preparation. In this review, the evidence for
      bacterial DNA fragments will be examined and suggestions for further studies will
      be described.

PMID- 19169025
TI  - Extracellular volume and aldosterone interaction in chronic kidney disease.
AB  - Since the advent of angiotensin-converting enzyme inhibitors and angiotensin
      receptor blockers, little attention has been given to the potential
      proinflammatory effects of aldosterone in high-volume states on the kidney and
      cardiovascular system. In order to be correctly interpreted, aldosterone levels
      require a volume cofactor which can now be determined by measurement of
      extracellular fluid volume by means of bioimpedance. Chronic kidney disease
      patients frequently have expanded extracellular volume (ECV) in the presence of
      elevated aldosterone levels. This combination may lead to cardiovascular and
      renal inflammation and fibrosis that can be mitigated by more precise control of
      ECV and/or blockade of the mineralocorticoid receptor.

PMID- 19169026
TI  - Cardiac disease in the dialysis patient: good, better, best clinical practice.
AB  - Proven strategies to reduce cardiovascular events and cardiac mortality in
      hemodialysis patients are given on the basis of pathophysiology. This is an
      overview of our clinical know-how acquired during the last 30 years. We try to
      answer the following questions: (1) how to reduce cardiovascular events and
      cardiac mortality in hemodialysis patients; (2) how to achieve regression of left
      ventricular hypertrophy, the most important predictor of sudden cardiac death;
      (3) how to manage iron status during full correction of renal anemia to prevent
      iron deficiency-induced reactive thrombocytosis, which is recognized to cause
      fatal stroke and cardiovascular thrombosis; (4) how to maintain responsiveness to
      erythropoiesis-stimulating agents during correction of renal anemia, thereby
      avoiding unnecessarily high doses and so reaching ultimate cost-effectiveness.
      CONCLUSION: Normalization of renal anemia is not responsible for increased risk
      of cardiovascular events/cardiac mortality. The inability to adequately address
      iron status in hemoglobin normalization studies and the underprescription of
      effective cardiac/antihypertensive medication might explain the adverse outcome.
      Effective cardiac/antihypertensive medication, intensive iron therapy during
      normalization of hemoglobin, optimized correction of metabolic acidosis and
      supplementation of vitamins which are involved in the energy metabolism should be
      considered to significantly improve the outcome of hemodialysis patients.

PMID- 19169027
TI  - The cardiorenal syndrome.
AB  - The term 'cardiorenal syndrome' (CRS) has increasingly been used in recent years
      without a constant meaning and a well-accepted definition. To include the vast
      array of interrelated derangements, and to stress the bidirectional nature of the
      heart-kidney interactions, the classification of the CRS today includes 5
      subtypes whose etymology reflects the primary and secondary pathology, the time
      frame and simultaneous cardiac and renal codysfunction secondary to systemic
      disease. The CRS can generally be defined as a pathophysiological disorder of the
      heart and kidneys whereby acute or chronic dysfunction in one organ may induce
      acute or chronic dysfunction in the other organ. Type I CRS reflects an abrupt
      worsening of cardiac function (e.g. acute cardiogenic shock or decompensated
      congestive heart failure) leading to acute kidney injury. Type II CRS describes
      chronic abnormalities in cardiac function (e.g. chronic congestive heart failure)
      causing progressive and permanent chronic kidney disease. Type III CRS consists
      in an abrupt worsening of renal function (e.g. acute kidney ischemia or
      glomerulonephritis) causing acute cardiac disorder (e.g. heart failure,
      arrhythmia, ischemia). Type IV CRS describes a state of chronic kidney disease
      (e.g. chronic glomerular disease) contributing to decreased cardiac function,
      cardiac hypertrophy and/or increased risk of adverse cardiovascular events. Type
      V CRS reflects a systemic condition (e.g. diabetes mellitus, sepsis) causing both
      cardiac and renal dysfunction. Biomarkers can help to characterize the subtypes
      of the CRS and to indicate treatment initiation and effectiveness. The
      identification of patients and the pathophysiological mechanisms underlying each
      syndrome subtype will help to understand clinical derangements, to make the
      rationale for management strategies and to design future clinical trials with
      accurate selection and stratification of the studied population.

PMID- 19169028
TI  - Today's approach to the critically ill patient with acute kidney injury.
AB  - The present review describes recent evidence on all aspects relating to acute
      kidney injury (AKI): epidemiology, definition, diagnosis, medical and
      extracorporeal therapy. AKI is often underrecognized, but its outcome still
      remains unfavorable. In this light, definition, classification and diagnosis of
      AKI are fundamental today and may be reliably based on recently proposed RIFLE
      (risk, injury, failure, loss of function, end-stage kidney disease)
      classification. Pharmacological therapy of AKI is still scarcely effective, but
      renal replacement therapy has progressed to a more accurate and safe treatment
      and new interesting high-level trials and observational studies have been
      performed and are reviewed and commented. In the near future, however, only
      increased awareness of AKI incidence and early treatment or prevention of kidney
      injury progression will hopefully improve outcome of critically ill patients with
      renal failure.

PMID- 19169029
TI  - Functional outcome in delusional Alzheimer disease patients. A systematic review.
AB  - BACKGROUND: In spite of the prevalence of delusions in Alzheimer's disease (AD)
      and their association with poor outcomes, there has been little study of the
      impact of delusions on real-world functioning. METHOD: A number of databases,
      including Psychlit and Medline, were searched using the keywords: delusions,
      functional outcomes, activities of daily living, dementia, and Alzheimer's
      disease. Studies were included in the review if they were in English, restricted
      to patients with AD, and addressed delusions and function. RESULTS: The review
      yielded a total of 6 studies, 3 of which showed a correlation between delusions
      and real-world functioning and 3 of which did not. CONCLUSION: A critical
      analysis of the existing studies suggests that there may be an association
      between delusions and impaired real-world functioning. We believe that 2 of the 3
      negative studies did not show an association due to issues relating to study
      design and the use of measures insensitive to executive impairment. This review
      highlights the future need for more scientifically rigorous studies to clarify
      this association, so as to ultimately improve treatment outcomes for patients.

PMID- 19169030
TI  - Cold and hot snare endoscopic techniques for removal of the Bravo pH monitoring
      capsule.
AB  - BACKGROUND: Currently, use of the Bravo capsule is a very common method for
      evaluating the gastroesophageal reflux because it has the advantage of being an
      intraesophageal catheter-free system. However, endoscopic removal of the capsule
      is necessary when technical problems or severe discomfort are present. Most
      frequently, endoscopists solve this problem by nudging the device with the tip of
      the endoscope to dislodge it; others have used a cold snare to produce traction
      on the capsule, and then tear the probe off. These techniques however are not
      free of complications. We report here the cold and hot snare techniques used in 4
      of our patients, which resulted in the successful removal of the capsule without
      complications. METHODS: The polypectomy cold snare procedure is a typical
      polypectomy method. The cold snare loops the mucosal pedicle and tightly closes
      it until sectioning is achieved. In the hot snare technique, a monopolar
      coagulating current is added to the previous procedure, making the resection more
      feasible when the cold snare is not sufficient. Finally, in both situations, the
      probe is removed from the esophagus with the same snare. CONCLUSIONS: The cold
      and hot snare techniques are safe and simple endoscopic procedures when the
      removal of the Bravo capsule is required. We recommend the cold snare method as a
      first option and the hot snare method in case the former fails.

PMID- 19169031
TI  - Assessment of viable tumour tissue attached to needle applicators after local
      ablation of liver tumours.
AB  - AIM: Local recurrence and needle track seeding are serious complications after
      local ablation for liver malignancies and potentially affect long-term survival.
      The aim of this study was to assess the incidence of viable tissue adherent to
      the needle applicators after ablation to gain insight into the possible
      mechanisms of local recurrence and needle track seeding. METHODS: A total of 40
      consecutive patients underwent 59 local liver ablations. Cells and tissue
      attached to the needle applicators were analysed for morphology (HE, PAP and
      Giemsa staining) and viability (G6PD staining). RESULTS: Macroscopic tissue
      adherence was visible following 31 of the ablative procedures, all with
      radiofrequency ablation. Four applications were performed percutaneously and 27
      during an open procedure. Morphologically intact tumour cells could be identified
      in 8 patients (20%), and viable tumour cells in 5 patients (12.5%).
      Morphologically intact tumour cells or viable tumour cells could only be
      demonstrated when track ablation was not performed. CONCLUSION: Viable tumour
      cells adherent to the needle applicators were found in an alarming 12.5% of
      patients after local ablation. We recommend track ablation not only after the
      procedure but also during any shifting and (re-)positioning to prevent shedding
      of viable tumour cells during or after ablation.

PMID- 19169032
TI  - Delirium after abdominal surgery at a surgical ward with a high standard of
      delirium care: incidence, risk factors and outcomes.
AB  - BACKGROUND: Although delirium is a common problem in elderly patients undergoing
      surgery, standard delirium care is not available in all wards. The object of this
      study was to determine the incidence, risk factors and outcomes of postoperative
      delirium among patients aged 65 and above undergoing elective abdominal surgery
      at a surgical ward with a high standard delirium care. METHODS: Prospective
      descriptive survey in 71 patients. The Delirium Observation Scale was used to
      screen for delirium. Patients were classified as having a delirium if they met
      the DSM IV-criteria. Delirious and nondelirious patients were compared and
      associated risk factors were calculated using logistic regression analyses.
      RESULTS: Incidence of postoperative delirium was 24%. Univariate analysis showed
      that age above 74 years, CST score, ASA score, length of ICU stay, length of
      hospital stay and number of complications were significant risk factors for
      delirium. Older age, however, was the only significant risk factor in
      multivariate analysis (OR 1.16; 95% CI 1.00-1.35; p = 0.05). Lastly, mortality
      was significantly higher in the delirium group (29.4 vs. 3.7%; p = 0.001).
      CONCLUSION: At a surgical ward with high standard delirium care, the incidence of
      delirium was 24% and mortality was higher in delirious patients undergoing
      elective abdominal surgery.

PMID- 19169033
TI  - Survival of patients with T3 stage III rectal cancer is significantly worse than
      T2 stage III rectal cancer. A new proposal of a subdivision of stage III rectal
      cancer.
AB  - BACKGROUND: The prognosis of T1 plus T2 stage III rectal cancer patients is
      better than that of T3 stage III rectal cancer patients. However, it is thought
      that T1 rectal cancer patients have a better prognosis than T2 rectal cancer
      patients. AIM: This study attempted to clarify the difference of the short- and
      long-term outcomes in T2 and T3 stage III rectal cancer patients deleting T1
      cancer. METHODS: The study demonstrated the potential predictors of the survival
      after surgery, the factors associated with T3 and T2, and the recurrence sites in
      134 patients with stage III rectal cancer who underwent surgery, including 111
      patients with T3 and 23 patients with T2. RESULTS: The disease-free survival
      (DFS) of the T3 stage III patients was worse than the T2 stage III patients (5
      year DFS rates, 52 vs. 78%; 10-year DFS rates, 43 vs. 78%; p =0.044). The maximum
      tumor size and operative blood loss were significant tumor characteristics
      associated with the depth of invasion (p =0.007,p =0.011,respectively). There was
      no significant difference in the recurrence sites after surgery between the two
      groups. CONCLUSION: As a result, a more detailed subdivision for stage III rectal
      cancer is considered necessary.

PMID- 19169034
TI  - POSSUM predicts survival in patients with unresectable pancreatic cancer.
AB  - BACKGROUND: The aim of this study was to evaluate the physiological and operative
      severity score for the enumeration of mortality and morbidity (POSSUM) for
      patients with unresectable pancreatic cancer and to analyze whether POSSUM can
      predict the long-term outcome in these patients. Such a scoring system could be
      useful to aid in the decision between surgical and endoscopic palliation.
      METHODS: Between January 1993 and December 2004, 241 patients were found to have
      unresectable pancreatic cancer during exploratory laparotomy and underwent a
      double bypass procedure consisting of a gastrojejunostomy and a
      hepaticojejunostomy. RESULTS: Overall, 64 of 240 patients (27%) had one or more
      complications after bypass surgery and 4 patients (2%) died. POSSUM predicted
      morbidity in 114 patients (47%). The observed:predicted (O:P) ratio for morbidity
      was 0.56 and the model had a significant lack of fit (p < 0.001) using a goodness
      of-fit analysis. The overall median survival was 7 months. The POSSUM scoring
      system was, however, an independent predictor of survival in multivariate
      analysis. CONCLUSIONS: Overall, POSSUM overpredicted morbidity but was an
      independent predictor of survival.

PMID- 19169035
TI  - Prenatal 3D ultrasound diagnostics in cleidocranial dysplasia.
AB  - A 34-year-old Caucasian woman with cleidocranial dysplasia (CCD) and a known
      family history of CCD was referred for an ultrasound examination in the first
      trimester of her second pregnancy. Molecular genetic analysis of the RUNX2 gene
      was non-informative. A routine 2D ultrasound examination carried out at a local
      hospital at gestational age 12 weeks showed no signs of CCD. A 3D ultrasound
      examination in week 15+4 showed a fetus with typical CCD features including large
      fontanelles, lack of nasal bones, clavicles without the typical S-form, as well
      as severe delay in calvarial ossification, especially in the midline. Serial 3D
      ultrasound examinations during pregnancy confirmed the diagnosis, and over time
      the manifestations became even more distinct. The diagnosis was clinically
      confirmed at birth. This case suggests that the typical craniofacial CCD traits,
      including wide unmineralized areas in the calvarial midline and missing nasal
      bones, are easily recognizable using 3D ultrasound as early as in week 15.

PMID- 19169036
TI  - Microstructural changes in uterine leiomyomas and myometrium: a diffusion
      weighted magnetic resonance imaging study.
AB  - Although morphological and histopathological changes in uterine leiomyomas have
      been investigated in detail, the microstructural disruptions could not be studied
      in the living organism. Diffusion-weighted magnetic resonance imaging (DWI) is a
      novel tool to assess microstructural changes in vivo. The aim of this study was
      to investigate and characterize the diffusional property of leiomyomatous tissues
      with DWI. Sixteen females with a total of 21 leiomyomas were imaged with a 1.5
      tesla clinical MR scanner. DWI images of leiomyomas, adjacent myometrial and
      myometrial tissues of healthy controls were obtained and quantified using
      apparent diffusion coefficient (ADC) maps. Mean ADC values of these groups were
      1,201, 1,684, 1,661 mm(2)/s x 10(-6), respectively. ADC values in leiomyomas were
      significantly lower than those observed in the myometrium (p < 0.001). Cut-off
      values produced 91% sensitivity and 100% specificity. As ADC values implied the
      presence of cytotoxic edema in leiomyomas, the technique was found to be
      promising in observing temporal variations in leiomyomas and to monitor even the
      most subtle effects of therapeutic interventions.

PMID- 19169037
TI  - Nerve growth factor and its monocyte receptors are affected in kidney disease.
AB  - Nerve growth factor (NGF) plays a critical role in both physiological and
      pathological conditions. Their biological effects are mediated by two receptors
      (NGF-R): TrkA and p75. We previously reported NGF and NGF-R overexpression in
      various renal disorders. The aim of the study was to determinate NGF levels and
      NGF-R expression in peripheral blood mononuclear cells from subjects affected by
      glomerulonephritis (GN) and by end-stage renal disease before and after
      hemodialysis (HD). We enrolled 48 patients with biopsy-proven diagnosis of GN and
      16 patients undergoing chronic HD. 25 subjects were enrolled as controls (C).
      Quantification of NGF in the serum samples was performed using NGF immunoassay.
      We demonstrated, for the first time, an increased NGF concentration in GN and HD
      patients compared to C. HD is able to restore serum NGF concentration. In GN,
      TrkA is overexpressed, whereas p75 did not show any difference versus C. By
      contrast in HD, TrkA expression is associated with increased p75 levels. In
      conclusion, NGF can act as protective factor against cytotoxic injuries. p75
      plays a role in both survival and death of cells, depending on absence of ligand,
      cytoplasmic/ligand interaction and interaction with TrkA. The present findings
      suggest that cell survival during cellular damage is dependent on co-expression
      of TrkA and p75 and independent of NGF concentration. Further studies are
      required to confirm these observations.

PMID- 19169038
TI  - Prevalence of spinocerebellar degenerations in the Hokuriku district in Japan.
AB  - BACKGROUND: The prevalence of disease subtypes of spinocerebellar degenerations
      (SCDs) varies between countries, and even between areas within a country. We
      report unprecedented epidemiologic data on SCDs in the Hokuriku district, which
      is located in the central, western part of Japan. METHODS: Clinical and genetic
      data on SCD patients were obtained via questionnaires distributed to all the
      departments of neurology, psychiatry and internal medicine in the Hokuriku
      district (n = 418). RESULTS: Among the SCD patients, autosomal dominant
      cerebellar ataxias (ADCAs) were noted in 40.4%, multiple system atrophy in 24.7%,
      cortical cerebellar atrophy in 13.3% and autosomal recessive cerebellar ataxia in
      0.3%. Genetically confirmed ADCA patients included those with Machado-Joseph
      disease (MJD)/spinocerebellar ataxia type 3 (SCA3; 63.3%), SCA6 (20.0%), ADCA
      linked to chromosome 16q22.1 (10.0%), dentatorubral pallidoluysian atrophy
      (4.4%), SCA1 (1.1%) and SCA2 (1.1%). MJD/SCA3 was highly prevalent in the Toyama
      prefecture of the Hokuriku district, accounting for 90% of genetically confirmed
      ADCAs by birthplace; MJD/SCA3 patients were concentrated in the Gosei area, the
      western part of the Toyama prefecture, giving an estimated prevalence of 19.1 per
      100,000 inhabitants. CONCLUSIONS: The Hokuriku district, especially the Gosei
      area of Toyama, had a surprisingly high relative frequency and prevalence of
      MJD/SCA3, which is comparable to that in the Azores, Portugal.

PMID- 19169039
TI  - Spinocerebellar degenerations in Japan. New insights from an epidemiological
      study.

PMID- 19169040
TI  - Community-based study of stroke incidence in the Valley of Aosta, Italy. CARe
      cerebrovascular Aosta Registry: years 2004-2005.
AB  - The purpose of our study was to determine the incidence of stroke, case-fatality
      rate and disability at 1 year in the Valley of Aosta (Italy) in the years 2004
      and 2005. All suspected strokes occurring between January 1, 2004, and December
      31, 2005, in the resident population of the Valley of Aosta were identified
      according to the WHO criteria for stroke and included in a stroke registry
      (Cerebrovascular Aosta Registry, CARe) after revision by a clinical panel.
      Multiple overlapping sources were used to ascertain the cases. In the study
      period, 553 incident strokes were registered. A CT scan was performed in 94.2% of
      cases. The crude annual incidence rate was 223 (95% CI 197-249) per 100,000
      inhabitants. After age and sex adjustment to the 'European' population, the
      stroke incidence rate was 126 (95% CI 106-146). In the 1-year follow-up, only a
      small number of patients with a first-ever stroke in their life time suffered a
      new event. Compared with the previous study performed in our region (Valley of
      Aosta) in 1989, a marked decline in the incidence rate was seen after adjustment
      to the 'European' population, and the 28-day case-fatality rate declined
      dramatically between 1989 and 2004-2005.

PMID- 19169041
TI  - Smoking cessation at 5 years after stroke in the North East Melbourne stroke
      incidence study.
AB  - BACKGROUND/AIMS: There is limited knowledge about smoking cessation after stroke.
      We examined smoking cessation and recall of smoking cessation advice among 5-year
      stroke survivors. METHODS: Interviews were conducted between May 2002 and May
      2004 with 5-year survivors from a population-based stroke incidence study
      undertaken from May 1 1997 to April 30 1999 in Melbourne, Australia. Data were
      gathered on smoking status at stroke onset, cessation advice recalled and periods
      of cessation up to 5 years after stroke. Cessation was determined by examining
      smoking status at stroke onset and at 5 years after stroke. RESULTS: Of the 441 5
      year stroke survivors, 343 (78%) had smoking data at follow-up. Fifty-one people
      were current smokers at stroke onset and 19 (37%) had quit smoking by 5 years
      after stroke. Of the 40 ever smokers who responded to a question regarding
      cessation advice, 40% (n = 16) could not recall receiving any such advice since
      their stroke. CONCLUSION: The majority of smokers continued to smoke at 5 years
      after stroke. Few smokers recalled smoking cessation advice. Given that receiving
      such advice can be the first step towards cessation, improvements in the delivery
      of advice to this high-risk group are needed.

PMID- 19169042
TI  - Classic risk factors for atherosclerosis are not major determinants for location
      of extracranial or intracranial cerebral atherosclerosis.
AB  - BACKGROUND: The prevalence of extracranial (EC) and intracranial (IC)
      atherosclerosis varies among races. Although several studies have sought to
      identify specific vascular risk factors that are associated with EC or IC
      atherosclerosis, the exact relationships are uncertain. This study aimed to
      determine if there are any specific risk factors for EC or IC atherosclerosis.
      METHODS: For this study, we considered 3,349 consecutive patients who had been
      entered into a stroke registry between January 1999 and June 2007. After the
      exclusion of patients who had not undergone angiography, patients with cardiac
      sources of embolism or other causes of stroke, and non-Koreans, we had a total of
      2,169 patients of single ethnicity with an angiographic analysis. Patients with
      atherosclerosis in both the IC and EC arteries (856 patients) were excluded.
      Finally, we identified 1,313 patients who had EC atherosclerosis (EC group, n =
      256), IC atherosclerosis (IC group, n = 566) or normal angiographic findings (no
      lesion group, n = 488). The frequency of risk factors and the demographic
      parameters were compared among these groups. RESULTS: When compared to the normal
      group, the IC group was associated with older age and hypertension, and the EC
      group was associated with older age, higher initial blood sugar and low-density
      lipoprotein cholesterol levels. However, in a direct comparison between the IC
      and EC groups, we did not observe any significant risk factors or variables
      except for a higher frequency of males and higher total cholesterol levels in the
      EC group. CONCLUSIONS: Vascular risk factors may not be major determinants of
      location for atherosclerosis in the EC or IC arteries.

PMID- 19169044
TI  - How common is essential tremor?

PMID- 19169043
TI  - Prevalence of essential tremor in a multiethnic, community-based study in
      northern Manhattan, New York, N.Y.
AB  - BACKGROUND: Our aims were to: (1) estimate the prevalence of essential tremor
      (ET) in a community-based study in northern Manhattan, New York, N.Y., USA; (2)
      compare prevalence across ethnic groups, and (3) provide prevalence estimates for
      the oldest old. METHODS: This study did not rely on a screening questionnaire.
      Rather, as part of an in-person neurological evaluation, each participant
      produced several handwriting samples, from which ET diagnoses were assigned.
      RESULTS: There were 1,965 participants (76.7 +/- 6.9 years, range = 66-102
      years); 108 had ET [5.5%, 95% confidence interval (CI) = 4.5-6.5%]. Odds of ET
      were robustly associated with Hispanic ethnicity versus white ethnicity [odds
      ratio (OR) = 2.19, 95% CI = 1.03-4.64, p = 0.04] and age (OR = 1.14, 95% CI =
      1.03-1.26, p = 0.01), i.e. with every 1 year advance in age, the odds of ET
      increased by 14%. Prevalence reached 21.7% among the oldest old (age > or = 95
      years). CONCLUSIONS: This study reports a significant ethnic difference in the
      prevalence of ET. The prevalence of ET was high overall (5.5%) and rose markedly
      with age so that in the oldest old, more than 1 in 5 individuals had this
      disease.

PMID- 19169045
TI  - Therapeutic intent in the conduct of phase I antineoplastic drug trials.

PMID- 19169046
TI  - Clinical benefit of new targeted agents in phase I trials in patients with
      advanced colorectal cancer.
AB  - BACKGROUND: Standard treatment for patients with advanced colorectal cancer
      (ACRC) includes fluoropyrimidines in combination with oxaliplatin or irinotecan.
      The addition of targeted agents such as bevacizumab and cetuximab to these
      chemotherapy backbones further improved outcome with survival rates. However,
      even after intensive treatment, most tumors will subsequently progress and some
      patients are offered experimental phase I therapies. PATIENTS AND METHODS: We
      retrospectively analyzed the outcome for 78 ACRC patients treated consecutively
      within 23 phase I trials at the Royal Marsden Hospital (RMH) between January 2004
      and January 2008. RESULTS: The median age was 62 years (range 26-78). After a
      median follow-up time of 21.4 weeks (range 1.7-115.6) the median progression-free
      survival and overall survival (OS) were 8.6 weeks (95% CI: 6.4-10.7) and 29.1
      weeks (95% CI: 15.7-42.5), respectively. 28.8 and 8.2% of the patients were
      assessed as having stable disease (SD) at 3 and 6 months, respectively. Patients
      with SD had an OS of 40.6 weeks (95% CI: 32.9-48.2) compared to 17.4 weeks (95%
      CI: 14.0-20.8, p = 0.017) for patients with progressive disease. CONCLUSION: A
      limited number of patients with ACRC who failed conventional treatments can
      derive clinical benefit by participating in phase I cancer trials, and the use of
      the RMH prognostic score can help to identify these patients.

PMID- 19169047
TI  - Histochemical detection of ischemia-like alterations induced in kidney tissue in
      vitro--different sensitivity to oxidant stress of glomerular ENTPD1 versus E5NT.
AB  - The expression of ENTPD1 (ecto-nucleoside triphosphate diphosphohydrolase) along
      the glomerular microvasculature of the kidney is downregulated in ischemic
      conditions, in contrast to E5NT (ecto-5'-nucleotidase), which may explain the
      increased tendency for intraglomerular microthrombus formation in vivo. It has
      been suggested that in ischemia, reactive oxygen species (ROS) affect glomerular
      ENTPD1, whereas E5NT seems less sensitive to oxidant stress. To test this
      hypothesis, a soluble ATP and ADP hydrolyzing enzyme solution (apyrase) [0.4
      U/ml] or 5'-nucleotidase solution [0.33 U/ml] as well renal tissue were exposed
      to ROS, generated by gamma-irradiation in vitro. The enzymes diluted in distilled
      water or cryostat rat kidney sections were exposed to gamma-irradiation (0.037
      Gy/s) for 0, 2, 5, 10, or 15 min, with or without supplementation of the ROS
      scavenger dimethylsulfoxide (DMSO). The enzyme activity of the samples was
      biochemically tested using standard methods, before and after irradiation. The
      reaction product of irradiated versus nonirradiated kidney sections was
      semiquantitatively evaluated after histochemical staining for either glomerular
      ENTPD1 or glomerular E5NT expression. The results show that the enzyme activity
      in samples of soluble apyrase was significantly decreased after irradiation. This
      effect was inhibited by DMSO. In contrast, 5'-nucleotidase activity showed only a
      limited decline of the activity curve after irradiation, which could also be
      restored following supplementation of DMSO. Glomerular ENTPD1 expression showed
      significant decrease after irradiation of kidney sections; again, this was
      inhibitable by DMSO. Glomerular E5NT activity was not altered by irradiation and
      DMSO supplementation did not affect its activity. It is concluded that soluble
      apyrase as well as the glomerular ENTPD1 are sensitive to oxidant stress, which
      may explain their downregulation in the ischemic condition in vivo. However,
      soluble 5'-nucleotidase and E5NT seem much less sensitive to ROS. This relative
      insensitivity of E5NT to oxidant injury may counteract ischemic injury by
      promoting local generation of adenosine in the ischemic micro-environment.

PMID- 19169048
TI  - Non-functioning pituitary adenomas infrequently harbor G-protein gene mutations.
AB  - BACKGROUND: Mutations of the genes encoding the alpha subunit of the stimulatory
      G protein (Gs) and of the inhibiting Gi2 protein (GNAS1 and GNAI2 genes,
      respectively) have been described in various endocrine neoplasias, including
      pituitary tumors. AIM: To search for mutations of GNAS1 and GNAI2 in a continuous
      series of non-functioning pituitary adenoma (NFPA) patients neurosurgically
      treated. SUBJECTS AND METHODS: The surgical samples of 22 patients who have been
      defined and characterized on a clinical, biochemical, histological, and
      immunohistochemical point of view have been processed for investigating the
      presence of the above mutations by PCR amplification of the hot spots exons 8 and
      9 of GNAS1, and exons 5 and 6 of GNAI2, followed by direct sequencing. Moreover,
      the promoter region of GNAI2, in order to assess the prevalence of single
      nucleotide polymorphisms (SNP), was investigated in the same series. RESULTS: A
      CGT>TGT mutation at codon 201 of GNAS1 gene in a single case of NFPA was found,
      but no mutation of GNAI2A was demonstrated. CONCLUSIONS: This finding suggests
      and confirms that G-protein mutations are rare and not crucial in NFPA
      development. Additionally, we found a silent SNP at codon 318 in the promoter of
      the Gi2alpha gene in one out of the 22 NFPA.

PMID- 19169049
TI  - Low free plasma levels of retinol-binding protein 4 in insulin-resistant subjects
      with polycystic ovary syndrome.
AB  - BACKGROUND: It has been shown in animals and in humans that retinol-binding
      protein 4 (RBP4) production from adipose tissue leads to generalized insulin
      resistance (IR). A more sensitive marker of circulating RBP4 is free plasma RBP4
      expressed by RBP4 to transthyretin (TTR) ratio, since in circulation RBP4 is
      bound to TTR. AIM: To investigate RBP4 levels in insulin-resistant women with
      polycystic ovary syndrome (PCOS) and to estimate free plasma RBP4 expressed by
      RBP4/TTR ratio. SUBJECTS AND METHODS: Thirty-five PCOS subjects were compared
      with 45 controls matched for age and body mass index (BMI). In each subject,
      fasting values of glucose, insulin, gonadotropins, estradiol, androgens, C
      reactive protein (CRP), RBP4, and TTR were determined. RESULTS: PCOS subjects in
      comparison to controls were more insulin-resistant [homeostasis model assessment
      for IR (HOMA-IR): 2.6+/-0.3 vs 1.9+/-0.1, p=0.043], and presented lower RBP4
      levels (28.3+/-1.1 vs 32.4+/-1.2 microg/ml, p=0.021) and RBP4/TTR ratio (0.26+/
      0.01 vs 0.31+/-0.01, p=0.0014). When RBP4 and RBP4/TTR values where stratified
      according to BMI status (obese, overweight, and lean subjects), it was noticed
      that both RBP4 and RBP4/TTR values in lean PCOS were significantly lower than in
      controls (RBP4: 25.0+/-5.5 vs 34.1+/-9.0 microg/ml, p=0.0063, RBP4/TTR: 0.25+/
      0.3 vs 0.35+/-0.1, p=0.016). No correlation was observed between RBP4 and
      RBP4/TTR with any hormonal or metabolic parameter including BMI. CONCLUSIONS:
      RBP4 and free plasma RBP4 expressed as RBP4/TTR ratio are statistically and
      significantly lower in insulin-resistant PCOS subjects in comparison to controls.
      Therefore, our findings do not confirm a link between IR, neither with RBP4 nor
      with free plasma RBP4 levels. The significance of these findings remains to be
      elucidated, since RBP4 might prove to have different actions, like other
      adipokines, from humans and rodents.

PMID- 19169050
TI  - Octreotide-LAR vs lanreotide-SR as first-line therapy for acromegaly: a
      retrospective, comparative, head-to-head study.
AB  - No head-to-head comparisons are available to analyze the efficacy of octreotide
      (LAR) and lanreotide (LAN) as first-line treatment of acromegaly.We compared the
      efficacy of these two drugs in 54 newly diagnosed patients (21 women, 33 men), 27
      treated with LAR (10-30 mg every 28 days) and 27 with LAN (60-90 mg/28 days), for
      12 months. Each LAR-treated patient was matched with one LAN-treated patient as
      for GH levels, sex, and age (+/-5 yr). Outcome measures were GH and IGF-I levels
      and tumor shrinkage and secondarily classical cardiovascular risk factors
      (total/HDL-cholesterol ratio, glucose tolerance), blood pressure and drug
      tolerability. In LAR- and in LAN-treated patients, respectively: GH and IGF-I
      were controlled in 21 (77.7%) and in 16 patients (59.3%; p=0.26); tumor shrinkage
      was absent (<25%) in 4 and 5 patients (p=1), mild (25.1-50%) in 9 and 12
      (p=0.57), moderate (50.1-75%) in 10 and 6 (p=0.37) and notable (>75%) in 4 and 4
      patients (p=1). The total/HDL-cholesterol ratio and insulin levels significantly
      decreased while glucose levels significantly increased in both groups. None of
      the patients with normal glucose tolerance at diagnosis developed diabetes
      mellitus. Side effects were mostly at the gastrointestinal level and were similar
      with both drugs. In conclusion, newly diagnosed patients with acromegaly treated
      with LAR and LAN have no significantly different prevalence of disease control,
      tumor shrinkage, improvement of cardiovascular risk markers and side effects.
      Therefore, both drugs can be safely employed as first-line therapy of acromegaly.

PMID- 19169051
TI  - Vascular endothelial growth factor in monochorionic twins with twin-twin
      transfusion syndrome.
AB  - OBJECTIVE: The purpose of this study was to determine vascular endothelial growth
      factor (VEGF) concentrations in the donor and the recipient in monochorionic twin
      pregnancies with twin-twin transfusion syndrome (TTTS) and single pregnancies in
      order to investigate the involvement of VEGF in the pathophysiology of TTTS.
      METHODS: Six twin pregnancies in 11 monochorionic twin pregnancies complicated
      with TTTS and 11 single control pregnancies were compared. Gestational age
      matched fetal blood and placental samples were obtained at birth. Serum VEGF
      concentration in the umbilical vein was measured by an enzyme-linked
      immunoabsorbant assay. Tissue protein expression of VEGF was determined by using
      immunohistochemistry. Western blot analysis and scanning densitometry were used
      to quantify and compare the VEGF expression in the terminal villi. RESULTS: Serum
      VEGF concentrations in the umbilical vein in both donors and recipients tended to
      be higher than those in the controls. Immunolocalization of VEGF in terminal
      villous placenta samples in both donors and recipients was mainly observed in the
      syncytiotrophoblastic layer and vascular endothelial cells with less intense
      staining in stromal cells. The expression of VEGF in the donor placenta increased
      significantly (p=0.006) compared to that in the control placenta, but the
      expression of VEGF in the recipients tended to be higher than in the controls.
      CONCLUSION: Intrauterine circulatory imbalance may induce changes in VEGF
      expression and these alterations may be involved in both donor and recipient in
      the pathogenesis of TTTS, due to the maintenance of hemodynamic stability between
      the circulation of the twins.

PMID- 19169052
TI  - Protective and therapeutic effects of swimming exercise training on diabetic
      peripheral neuropathy of streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Diabetic peripheral neuropathy (DPN) is a typical complication of
      diabetes. No definitive treatment and prevention of DPN has been established, and
      very few data on the role of exercise training on DPN have been reported. AIM OF
      THE STUDY: The protective and therapeutic effects of aerobic physical activity on
      the development of DPN in Type 1 were investigated. METHODS: Rats were assigned
      to 5 groups: C (control), E (exercise), D (diabetic), DEx (exercise after
      diabetic), ExD (diabetic after exercise); C containing 10 animals and E, D, DEx,
      ExD containing 15 animals. Diabetes was induced with streptozotocin (STZ) (45
      mg/kg, ip). Development of diabetes was confirmed by measuring blood glucose
      levels 2 days after STZ treatment. Body weights of all the animals were evaluated
      weekly throughout the experiment. Motor dysfunction defined by a significant
      increase in compound muscle action potential (CMAP) latency was recorded. The
      amplitude of CMAP which mainly reflects axonal dysfunction was also measured
      using standard techniques. Sciatic nerve morphometry and blood glucose levels
      were analyzed in all the groups. RESULTS: Blood glucose level significantly
      increased 2 days after STZ injection. All diabetic rats showed decreased body
      weight compared to control rats. An increase in motor latency of CMAP and a
      decrease in amplitude of CMAP, indicative of neuropathy, were seen in STZ rats.
      On the completion of the study (the 56th day post-STZ), histological examination
      revealed significant myelin loss (thinner myelin) in sciatic nerves of STZ rats.
      Treatment with swimming exercise had no effect on glycemic control but restored
      body weight, CMAP amplitude, CMAP latency or motor dysfunction in the diabetic
      animals. CONCLUSIONS: This study suggests that swimming exercise training has
      protective and therapeutic effects on DPN of STZ-induced diabetic rats.

PMID- 19169053
TI  - Prevalence and risk factors for overweight and obesity in a population of Italian
      schoolchildren: a longitudinal study.
AB  - Prevalence of childhood overweight and obesity have dramatically increased
      worldwide in the last decades. Overweight and obesity are the result of a complex
      interaction between genetic and environmental factors. The aim of our
      longitudinal study was to assess the prevalence of overweight and obesity in a
      population of Italian schoolchildren followed for 2 years and to identify main
      risk factors for obesity onset and persistence in childhood. We enrolled 632
      children (males /females= 345/287), aged 3 to 8 yr.Weight and height were
      measured at time 0, 1 (1 yr later), and 2 (2 yr later). Overweight and obesity
      were defined using body mass index (BMI) (Italian growth charts). Data collected
      included: birth weight, gestational age,maternal weight gain during pregnancy,
      breast feeding, parents' BMI, educational level, and occupation type. At time 0,
      1, and 2 the prevalence of overweight was 22%, 22%, and 25%, respectively, and
      the prevalence of obesity was 7%, 8%, and 8%, respectively. During follow-up
      62%of children remained normal weight, 24% was always overweight or obese, 9%
      became overweight, while only 5% of overweight subjects became normal weight.
      Male gender, maternal weight gain during pregnancy >10 kg, parental
      overweight/obesity were positively associated with the presence of overweight
      during the entire follow-up. On the contrary, being small for gestational age at
      birth was negatively related to persistence of overweight. No influence was found
      for being breastfed, for parental low educational level, and manual occupation. A
      large prevalence of overweight/obesity was observed in Italian schoolchildren.
      Gender, maternal weight gain during pregnancy, and parents' BMI were the
      strongest predictors of the persistence of child overweight and obesity.

PMID- 19169054
TI  - Body fat in men with prolactinoma.
AB  - OBJECTIVE: (a) To evaluate body fat in men with prolactinoma and healthy
      controls, using whole body dual energy x-ray absorptiometry (DXA), and (b) to
      correlate DXA results with anthropometry and clinical aspects of male
      prolactinomas. MATERIAL AND METHODS: A cross-sectional study was performed in two
      University referral centers. Eleven newly-diagnosed men with prolactinoma and 9
      with normal PRL levels due to dopamine agonist treatment were submitted to DXA
      and blood analysis (PRL, testosterone, dihydrotestosterone, estradiol, and SHBG)
      by the time of their clinical evaluation. They were compared with 14 control men
      of similar age and body mass index distribution. RESULTS: Newly-diagnosed men
      with prolactinoma had higher fat percentage in the arms and the total body, when
      compared with patients treated with dopamine agonists and controls. The former
      group also presented higher fat percentage in the legs than the controls. Truncal
      fat percentage of the newly-diagnosed patients was lower than the dopamine
      agonist treated group. The 3 groups had similar android and gynoid fat contents.
      Fat percentage of the 6 sites correlated with PRL, testosterone, and
      dihydrotestosterone levels. CONCLUSION: Newly-diagnosed men with prolactinomas
      had higher body fat content. Body fat was linked to disease control, especially
      to the PRL and androgen levels. Consequently, adequate control of
      hyperprolactinemia should be pursued in order to reduce the risk of obesity and
      its metabolic complications in men with prolactinoma.

PMID- 19169055
TI  - Hypovitaminosis D and secondary hyperparathyroidism in resident physicians of a
      general hospital in southern Brazil.
AB  - OBJECTIVES: To evaluate the prevalence of hypovitaminosis D and secondary
      hyperparathyroidism in resident physicians of a general hospital in southern
      Brazil and identify associated factors. DESIGN: Cross-sectional study.
      POPULATION: Resident physicians of Hospital de Clinicas de Porto Alegre, Porto
      Alegre, southern Brazil. PARTICIPANTS: Seventythree subjects age 26.4+/-1.9.
      MEASUREMENTS: Serum PTH, 25- hydroxyvitamin D [25(OH)D], total calcium,
      phosphorus, magnesium, creatinine, and alkaline phosphatase were measured. In
      addition calcium, creatinine, and magnesium were measured in urine. Fractional
      excretion of calcium and magnesium were calculated. Calcium intake was estimated
      by a food intake questionnaire. RESULTS: Mean serum levels of 25(OH)D were 17.9+/
      8.0 ng/ml and 57.4% presented 25(OH)D below 20 ng/ml. Secondary
      hyperparathyroidism, defined as serum PTH > or =48 pg/ml and normal or low serum
      calcium, was identified in 39.7% of the individuals. Mean serum levels of
      magnesium were higher (p=0.02) and the fractional excretion of calcium was lower
      (p<0.001) in individuals with secondary hyperparathyroidism. Serum PTH levels
      were positively correlated with body mass index (r=0.33 and p=0.006) and serum
      magnesium levels (r=0.33 and p=0.02) and negatively correlated with serum 25(OH)D
      levels (r=-0.33 and p=0.008), estimated calcium intake (r=-0.25 and p=0.04), and
      fractional excretion of calcium (r=-0.34 and p=0.009). CONCLUSION: Vitamin D
      deficiency and secondary hyperparathyroidism was very common in resident
      physicians. Therefore, measures to prevent this situation should be recommended.

PMID- 19169056
TI  - Changes and effects of plasma arginine vasopressin in traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a common disease accompanied by
      chronic morbidity and mortality. The pathological mechanism and effective
      pharmacological treatments of TBI remain undetermined. It is suggested that AVP
      is involved in TBI. It is thus interesting to investigate the changes and effects
      of plasma AVP in clinical trials. METHODS: The serum concentrations of AVP, serum
      electrolytes, and serum osmolarity in a total of 23 TBI patients were dynamically
      monitored (on admission, Day 1, Day 3, and Day 5). Relationship between AVP and
      severity of brain injury and functional outcome were evaluated, respectively.
      RESULTS: The mean AVP serum concentrations in the TBI group were significantly
      higher than those recorded in the control (CTRL) group on intensive care unit
      (ICU) admission and Day 1 (p<0.05). On Day 3 and Day 5, the differences between
      those groups were not significant (p>0.05). The negative correlations were found
      between sodium and AVP (r=-0.35; p<0.05) and between osmolarity and AVP (r=-0.42;
      p<0.05). In poor outcome group, the mean AVP serum concentrations were
      significantly higher than in good outcome group and CTRL group (p<0.05). A
      statistically significant correlation was also found between AVP on ICU admission
      and the initial Glasgow Coma Scale (r=0.47; p<0.05). CONCLUSION: We suggest that
      AVP is involved in the pathophysiology process of secondary brain damage after
      TBI. It seems that AVP antagonist is a promising target for the treatment of TBI,
      while further studies should be carried out.

PMID- 19169057
TI  - Hemodynamic alterations and wall properties in large arteries of young,
      normotensive, and non-obese women with polycystic ovary syndrome.
AB  - Young, normotensive, and non-obese women with polycystic ovary syndrome (PCOS)
      may present abnormal hemodynamic alterations (HA). The purpose of this study was
      to investigate heart rate (HR), intima-media thickness (IMT), and diameter (DCCA)
      in the common carotid arteries (CCA), flow velocities, and resistance index in
      both extracranial carotid and vertebral arteries (VA), in the abdominal aorta
      (AO) and in the renal arteries (RA) in PCOS women and matched controls. This was
      a case-control study conducted at a tertiary University Hospital. We studied 53
      PCOS women and 53 healthy matched volunteers as controls. The previously reported
      parameters were assessed using color Doppler ultrasonography. HR, IMT in the CCA,
      and peak systolic velocity in all examined arteries were significantly increased
      in PCOS women compared to controls. On the contrary, DCCA was significantly
      decreased in PCOS women compared to controls. End diastolic velocity (EDV) in
      both VA and RA, in the AO and in the left extracranial carotid system was
      significantly increased in the PCOS group compared to controls. Furthermore, the
      peripheral resistance (PR) of AO and right external carotid artery was also found
      to be increased while in both RA and in left VA, PR was decreased. No further
      statistical significant HA in EDV and PR were noted. The results of this study
      provide evidence for a mild hyperdynamic circulation in young, normotensive, non
      obese women with PCOS compared to controls, indicating a mild sympathetic
      activation at an early age, which may be an underlying cause of hypertension and
      cardiovascular risk.

PMID- 19169058
TI  - The role of non-invasive dynamic tests in the diagnosis of Cushing's syndrome.
AB  - OBJECTIVE: To evaluate the role of non-invasive dynamic tests in the diagnosis
      and differential diagnosis of Cushing's syndrome (CS). METHODS: We studied
      laboratory features of 74 patients with endogenous CS, subdivided as follows: 46
      (62.1%) with Cushing's disease (CD), 21 (28.3%) with an adrenal tumor, and 7
      (9.5%) with ectopic ACTH syndrome (EAS). RESULTS: In 100% of cases of CS we found
      serum cortisol levels greater than 1.8 microg/dl after low-dose dexamethasone
      suppression tests (LDDST), as well as elevation of midnight serum or salivary
      cortisol. However, urinary free cortisol was normal in 11.5% of patients. ACTH
      levels were suppressed in patients with adrenal tumors, normal or high in CD and
      invariably increased in EAS. After the 8-mg overnight dexamethasone suppression
      test (HDDST), serum cortisol suppression >50% was observed in 79.5% of cases of
      CD and in 28.6% of subjects with EAS, whereas cortisol suppression >80% was only
      found in CD. After stimulation with CRH or desmopressin an ACTH rise > or =35%
      occurred in 86.5% of individuals with CD and 14.3% of those with EAS, whereas an
      ACTH rise > or =50 achieved 100% specificity. Moreover, the combination of serum
      cortisol suppression >50% after HDDST and an ACTH increase > or =35% after the
      administration of CRH or desmopressin only occurred in CD. CONCLUSION: Our
      findings demonstrate that LDDST had 100% sensitivity for the diagnosis of CS and
      that HDDST and stimulation tests with CRH or desmopressin may be very useful for
      confirmation of CS etiology when analyzed together or when more stringent cut
      offs are used.

PMID- 19169059
TI  - Sympathovagal imbalance in transsexual subjects.
AB  - CONTEXT: Autonomic nervous system imbalance is related to cardiovascular risk.
      Heart rate variability (HRV) indexes are associated with age, race, and sex, but
      the role of sex hormones is still unknown. OBJECTIVE: To evaluate sympathovagal
      balance (SB) in transsexuals. PATIENTS: Eighteen transsexual subjects, 12 male-to
      female (group 1) and 6 female- to-male (group 2), compared with 34 age-matched
      controls: 17 males (group 3) and 17 females (group 4). Autonomic testing of SB
      was performed by Power Spectral Analysis (PSA) of HRV in clinostatism (c) and
      orthostatism (o). PSA identifies power peaks: high frequency (HF) expresses vagal
      activity, while low frequency (LF) expresses sympathetic activity. RESULTS: Group
      1 showed lower LFc than groups 2, 3, and 4 (p<0.001, p=0.05, p<0.001,
      respectively), and lower LFo than groups 3 and 4 (p=0.01); HFc was lower than in
      groups 2, 3, and 4 (p=0.02, p=0.02, p<0.001, respectively), and HFo was lower
      than in groups 3 and 4 (p<0.001). LFo/HFo ratio was higher in group 1 than in
      group 4 (p<0.001). No differences emerged between groups 2 and 3. Group 2 showed
      lower HFo than group 4 (p=0.03), and a higher LFo/HFo ratio (p=0.01). Group 3
      showed lower HFo and HFc than group 4 (p=0.02, p=0.05, respectively), and a
      higher LFo/HFo ratio (p=0.03). CONCLUSION: In this study we found a sympathovagal
      imbalance due to a reduced sympathetic and parasympathetic influence on heart
      rate. Sex hormone therapy per se may play a role in this imbalance, and HRV
      measurement could be useful in detecting cardiovascular risk in transsexuals.

PMID- 19169060
TI  - Association of comorbid depression, anxiety, and stress disorders with Type 2
      diabetes in Bahrain, a country with a very high prevalence of Type 2 diabetes.
AB  - This study examined the association of depression, anxiety, and stress with Type
      2 diabetes (T2DM) in Bahrain, an island-country with a very high prevalence of
      T2DM. This was a cross-sectional study involving administering Depression Anxiety
      Stress Scales (DASS)-21 structured depression, anxiety, and stress scale to 143
      T2DM patients and 132 healthy controls. Higher proportion of T2DM patients were
      found in the mild-moderate and severe- extremely severe depression (p=0.002),
      anxiety (p<0.001), and stress (p<0.001) groups. Chronic disease and disease
      duration were significantly associated with the 3 disturbances, while employment
      status was associated with anxiety and depression. Logistic regression analysis
      showed that anxiety, depression, and stress were associated with T2DM after
      adjusting for all variables, while age was the only significant variable
      associated with stress. These results suggest a positive contribution of T2DM to
      increased depressive and/or anxiety and/or stress disorders among the patients
      examined, thereby recommending counseling for T2DM patients.

PMID- 19169061
TI  - Role of GST and NAT2 polymorphisms in thyroid cancer.
AB  - Genetic polymorphisms have shown to be susceptibility factors playing an
      important role in the development of most cancers. Nevertheless, as far as we
      know, only few studies have been conducted linking thyroid cancer incidence and
      GST polymorphisms, and no data are available on the possible association between
      NAT2 polymorphisms and thyroid cancer risk. The possible relationship between
      polymorphism at the GSTM1, GSTT1, GSTP1, and NAT2 genes and increased
      susceptibility to thyroid cancer has been evaluated in 176 thyroid cancer
      patients and 167 healthy controls, all from the urban district of Barcelona
      (Spain). The results indicate a clear role of the C481T change, present in
      several NAT2*5 alleles [odds ratio (OR)=0.58; 95% confidence interval (95%
      CI)=0.35-0.98]. Thus, those individuals carrying this change are less prone to
      develop thyroid cancer, mainly of the papillary type. In addition, there is a
      tendency towards the over-representation of the GSTM1 null genotype among thyroid
      cancer patients, particularly in those patients with papillary type tumor. The
      same is observed for the GSTM1 and GSTT1 null genotypes combination, and for
      other combinations with different NAT2 polymorphisms. The combinations involving
      the NAT2*6 and NAT2*7 genotypes showed the most important effect, and individuals
      carrying both alleles present a higher risk of thyroid cancer (OR=7.36; 95%
      CI=0.85-63.47), mainly for the follicular type (OR=17.94; 95% CI=1.34-238.70).
      The combination of NAT2*5 with NAT2*7 was also found to increase 5.26 (95%
      CI=1.07-25.76) times the risk of thyroid cancer. In conclusion, our results show
      that NAT2 polymorphisms play a significant role in thyroid cancer risk
      modulation.

PMID- 19169063
TI  - A randomised controlled clinical trial of nurse-, dietitian- and pedagogist-led
      Group Care for the management of Type 2 diabetes.
AB  - AIM: To verify if Group Care, a model to manage Type 2 diabetes (T2DM) by
      systemic continuing group education, can be administered by nurses and dieticians
      under pedagogic guidance, and improve metabolic control, quality of life, Locus
      of Control, and insulin resistance. MATERIAL AND SUBJECTS: Twenty-five patients
      with non-insulin-treated T2DM were randomized to Group Care and 24 to continued
      habitual individual care and education delivered by a diabetes specialist and
      pedagogist, respectively. Six nurses and 1 dietician received training by an
      accredited programme, a detailed operating manual and pedagogical supervision
      throughout the study. Follow-up was for 2 yr and included measurements of fasting
      blood glucose, glycated hemoglobin (HbA1c), body mass index, waist circumference,
      lipids, creatinine, blood pressure, serum insulin, homeostasis model assessment
      (HOMA) index of insulin resistance, health behaviors, quality of life, state and
      trait anxiety, and Locus of Control. RESULTS: One patient on Group Care and 3
      controls dropped out. At the end of study, the patients on Group Care had lower
      HbA1c (7.6+/-0.8 vs 8.4+/-1.3, p<0.05), insulin (18.0+/-9.6 vs 24.3+/-13.7,
      p<0.001), HOMA index (6.9+/-5.4 vs 9.2+/-6.6, p<0.05), and fatalistic attitude
      (17.2+/-5.9 vs 24.9+/-4.2, p<0.001) and better quality of life (65.0+/-11.0 vs
      78.4+/-19.6, p<0.001) than controls. CONCLUSIONS: Group Care delivered by trained
      nurses and dietitian is associated with better outcomes than those obtained by a
      medically and pedagogically qualified team. It may offer a model for health
      operators to re-organize clinical practice and for patients to improve lifestyle
      and strengthen the therapeutic alliance with their carers.

PMID- 19169062
TI  - Prognostic factors in patients with papillary thyroid carcinoma.
AB  - BACKGROUND: Papillary thyroid carcinomas are associated with metastases and
      decreased survival in a small group of patients. AIM: The aim of this study is to
      determine the factors associated with recurrences/metastases in papillary thyroid
      carcinoma patients. SUBJECTS AND METHODS: One hundred and thirty-one patients
      with papillary thyroid carcinoma were evaluated retrospectively. The diagnosis
      was papillary microcarcinoma (PMC) in 48 patients. All patients had undergone
      near-total/total thyroidectomy. Radioactive iodine was given to 103 patients. Age
      at diagnosis, gender, previous history of thyroid disease, tumor stage,
      histopathological characteristics of tumor and initial treatment strategies were
      evaluated. RESULTS: Recurrences/metastases developed in 17 patients during follow
      up. Recurrences developed at a significantly higher percentage in patients with a
      tumor stage >T1 and patients with lymph node metastasis at presentation. No
      significant difference was observed in recurrence ratio between patients with PMC
      and patients with a tumor diameter > or =1cm. In the Cox-regression analysis only
      the advanced tumor stage (>T1) and presence of lymph node metastases were found
      to be significant predictors for recurrence (univariate analysis, odds ratio
      =4.02 and 3.15, respectively). However, multivariate analysis did not reveal any
      significant independent predictors. According to the Kaplan- Meier survival
      analysis, lymph node metastases at presentation were associated with a decrease
      in recurrence-free survival at statistical significance (p=0.05). No mortality
      was observed during follow-up. CONCLUSION: Papillary thyroid carcinoma leads to
      recurrences/metastases in a small group of patients. Initial characteristics of
      the patients--i.e. presence of lymph node metastases--may predict
      recurrences/metastases in these patients.

PMID- 19169064
TI  - A common variant in the FTO gene is associated with obesity in the Uyghur
      population.

PMID- 19169065
TI  - The interrater reliability of rating non-exercise activity of inpatients with
      eating disorders using a visual analogue scale.
AB  - BACKGROUND: Non-exercise activity thermogenesis (NEAT) is the energy expended by
      body movement, other than sleeping, eating or sports-like activities. The obese
      have been reported to have a lower NEAT (walking, standing, and fidgeting) than
      controls. We hypothesize that an elevated NEAT could explain why some patients
      with anorexia nervosa are resistant to weight gain. OBJECTIVE: To evaluate the
      interrater reliability of a rating of non-exercise activity of inpatients with
      eating disorders (ED) using a visual analogue scale (VAS). METHOD: Health care
      providers were asked to rate the non-exercise activity of inpatients by marking a
      VAS. RESULTS: Eight patients were individually rated by 10 clinicians. Results
      were analyzed using the intraclass correlation coefficient (ICC) and Cohen's
      multi-rater kappa statistic (kappa). The ICC(3,k) was 0.257 (p<0.01) and 0.708
      (p<0.01) for average measures. DISCUSSION: The ratings of NEAT using a VAS were
      not reliable between clinicians. This indicates that the ward staff, even on a
      specialized ED unit, cannot reliably estimate non-exercise activity and
      physiological measurements should be used.

PMID- 19169066
TI  - Is there evidence that religion is a risk factor for eating disorders?
AB  - OBJECTIVE: Is there evidence that religion is a risk factor for eating disorders?
      METHODS: A literature search was performed to examine whether there is an
      association between religion and eating disorders. RESULTS: There were some cross
      sectional studies, case studies, and anthropological commentaries reporting
      eating disorders in various cultures and religions. Religious affiliation was
      usually reported as an incidental finding but not analyzed. A number of
      prevalence studies were reported from Islamic communities. This raises the
      possibility that young Muslim women have a higher prevalence of elevated EAT
      scores compared to non-Islamic women. CONCLUSION: This literature search raises
      the possibility that there is an association between Islamic affiliation and
      positive screening for eating disorder behaviors. This supports the hypothesis
      that the effect of culture on eating disorders may be religious as well as
      secular. Carefully designed studies of the prevalence of eating disorders in
      multicultural populations with multiple religious affiliations may help further
      clarify the relationship between religion and eating disorders.

PMID- 19169067
TI  - Parotid gland enlargement in eating disorders: an insensitive sign?
AB  - OBJECTIVE: To study, using magnetic resonance imaging (MRI), the parotid glands
      of patients who self-induce vomiting and in particular to observe the effects of
      cessation of this behaviour. The morphological features and composition of
      enlarged parotid glands in this group, compared with normal controls, were also
      examined. METHOD: MRI scans of the parotid glands were performed on 5 controls
      and 5 subjects with a purging form of eating disorder, at cessation of vomiting
      and 6 to 9 weeks later. RESULTS: Parotid volumes are accurately measured using
      MRI. Enlarged parotids are not a consistent feature of subjects with eating
      disorders who self-induce vomiting. CONCLUSION: Absence of salivary gland
      enlargement does not exclude significant vomiting behaviour and clinicians should
      remain alert to the possibility of undisclosed vomiting.

PMID- 19169069
TI  - The impact of recalled elementary school height and weight on later weight
      concerns.
AB  - Although overweight children and adolescents experience a number of immediate
      difficulties, little research has investigated the long-term psychological
      consequences for individuals who were overweight as children or adolescents
      despite their weight status as young adults. The goal of this study was to
      examine the relations between individuals' retrospective reports of their weight
      and height during elementary and high school, and their past and current weight
      concerns. It was expected that individuals who recall being overweight as a child
      or adolescent would have more weight concerns than their peers who recall being
      normal weight, even after controlling for current body size. Participants were
      174 females and 61 males, ranging in age from 18-20 (M=18.66 yr, SD=0.63). For
      females, perceived elementary school weight in comparison to their peers
      significantly predicted current weight concerns, p<0.05. For males, perceived
      elementary school height in comparison to their peers significantly predicted a
      history of weight concerns, p<0.05. Retrospective height and weight in high
      school did not impact current weight concerns for either males or females.

PMID- 19169068
TI  - The relation of body dissatisfaction to salience of particular body sizes.
AB  - OBJECTIVE: Research examining body image schemas has found that individuals high
      in body dissatisfaction direct increased attention toward body shapes relative to
      neutral stimuli. However, it is not known whether attention is attracted to
      particular body shapes over others (e.g., thin or obese). The present study
      examined whether body dissatisfaction would moderate the extent to which women
      find thin, average, and/or obese body sizes salient. METHOD: Women with high and
      low body dissatisfaction (N=32) completed an indirect cognitive task assessing
      the relative salience of different body sizes (thin, average, obese). RESULTS:
      Degree of body dissatisfaction was inversely related to frequency estimates of
      obese body sizes; highly dissatisfied participants found obese body sizes less
      salient. CONCLUSION: These results highlight the importance of examining the
      salience of specific body sizes. The present study has implications for
      understanding cognitive aspects of social comparison and body dissatisfaction.

PMID- 19169070
TI  - Night eating status and influence on body weight, body image, hunger, and
      cortisol pre- and post- Roux-en-Y Gastric Bypass (RYGB) surgery.
AB  - Night Eating Syndrome is a common disorder in severely obese individuals and may
      be associated with hypothalamic pituitary adrenal (HPA) axis dysregulation. This
      study compared night eaters (NE) and comparably obese controls (C) pre- and post
      Roux-en- Y Gastric Bypass surgery at 2 and 5 months, following an overnight fast
      on hormonal measures associated with HPA axis and related appetite and
      psychological measures. There were 24 (10 NE, 14 C) clinically severely obese
      participants (body mass index =47.0+/-8.4 SD). At pre-surgery baseline, afternoon
      fasting hunger ratings differed significantly and were lower for NE than for C
      (p=0.01). Eight of the participants (4 NE, 4C) returned for all 3 study visits.
      At 5 months post-surgery, NE and C did not differ in weight loss, reductions in
      waist circumference, insulin levels, and insulin resistance (homeostasis model
      assessment). However, NE as compared to C, did not improve in self ratings of
      body image (p<0.05), and had significant increases in fasting afternoon cortisol
      levels 5 months after surgery (p=0.01).

PMID- 19169071
TI  - Family therapy in the treatment of adolescent anorexia nervosa: current research
      evidence and its therapeutic implications.
AB  - From the outset, the systemic and family movement has expressed an interest in
      eating disorders, more specifically anorexia nervosa, establishing causal links
      between family functioning and aetiology and advocating family therapy as the
      treatment of choice for this disorder. Because of high consistency between its
      explanatory and therapeutic dimensions, this model continues to dominate our
      conceptualizations and clinical practice, in spite of a lack of empirical
      support. This article summarizes present empirical evidence concerning both
      family functioning (explanatory dimension) and the effectiveness of family
      therapy (therapeutic dimension) in anorexia nervosa, and describes resulting
      changes in theoretical and clinical perspectives. A model of evidence-based
      family therapy is presented and several unresolved issues are raised. Overall,
      this overview of the literature supports the use of therapeutic models that are
      more flexible and normative, less guilt-inducing, more diversified (eclectic and
      integrative), and more rooted in the empirical literature.

PMID- 19169072
TI  - Night eating patterns of patients with bulimia nervosa: a preliminary report.
AB  - OBJECTIVE: This preliminary study examined nighttime eating behavior among
      patients with bulimia nervosa (BN). METHOD: The nighttime eating behavior of 31
      females (age: 17-49 yr) enrolled in an outpatient cognitive-behavioral treatment
      study for BN was assessed with the Night Eating Questionnaire (NEQ); patient
      subgroups were compared on the NEQ, Beck Depression Inventory, and Eating
      Disorder Inventory, and effect sizes were derived. RESULTS: Nighttime eating
      behavior was common. Sixteen patients (52%) reported evening hyperphagia,
      nocturnal ingestions of food, or both night eating behaviors. Clinically
      interesting patterns emerged on symptom assessments, although effect sizes were
      small. DISCUSSION: The nighttime eating behavior of individuals with eating
      disorders should be examined further. These preliminary findings suggest that
      current conceptualizations of the night eating syndrome are limited by research
      which has often excluded patients with primary diagnoses of eating disorders.

PMID- 19169074
TI  - Comparison of middle-age and young women inpatients with eating disorders.
AB  - The aim of the study was to compare clinical presentations of eating disorders
      (ED) in midlife vs. younger inpatients. The sample consisted of 604 inpatients,
      302 admitted to treatment at the age of 40 or older, and 302 admitted between
      ages 18-25, a more common ED age. Results suggested several unique features of
      midlife vs. younger ED inpatients: significantly more diagnoses of anorexia
      nervosa, both subtypes, and fewer diagnoses of bulimia nervosa; greater ED
      severity but fewer body image issues and less body image distortion; greater
      emotional and behavioral overcontrol and symptom denial; more bipolar and major
      depressive disorders, suicidality, and sexual abuse histories; a trend toward
      greater misuse of calming/sedating substances; and fewer maturation issues. The
      corresponding needs among midlife ED patients for specialized assessment and
      treatment interventions are considered.

PMID- 19169073
TI  - Comparative study of rate of weight loss among premorbid and healthy restrictive
      eaters.
AB  - Initial body mass index (BMI) and rate of weight loss are compared between
      cohorts of pathological and healthy dieters. The eating disordered sample
      consists of young adults reported in case studies in the past ten years with a
      primary diagnosis of anorexia nervosa (AN). The healthy dieters were adolescents
      who participated in the National Longitudinal Survey of Adolescent Health and
      indicated at the time of study enrollment that they were trying to lose weight.
      At diet initiation, the anorexic sample had a mean BMI (kg/m2) of 20.5 while the
      healthy dieters had a mean of 24.8. The median rate of weight loss was -1.87 kg
      per month (1 pound per week) for individuals later diagnosed with AN, while the
      median weight change was 0.24 kg per month for the Add Health dieters, reflecting
      an actual gain of 0.13 pounds per week. These findings suggest that measurable
      physiological characteristics during the early phase of a diet could be
      predictive of pathological food restriction.

PMID- 19169075
TI  - Efficacy of inpatient treatment in severely malnourished anorexia nervosa
      patients.
AB  - OBJECTIVE: Our aim is to present clinical results achieved with an intensive
      treatment programme for severe anorexia nervosa (AN) patients at risk of severe
      disability or death. Aims of the treatment are to remove life threatening
      conditions, physical and nutritional rehabilitation, and psychological and
      relational rehabilitation. METHODS: We present an observational retrospective
      study of a cohort of 99 consecutive patients affected by severe AN [according to
      Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)] and a body
      mass index (BMI) <or=13.5 kg/m2 treated by a multidisciplinary comprehensive
      medical, nutritional, psychological treatment. Intensive treatment (inpatient day
      and night and day hospital care) of variable length, with resort to enteral
      nutrition if needed, ends by achieving a BMI of at least 18 kg/m2. Outpatient
      care phase follows. Main goals were the recovery of BMI and the ability to
      maintain it. RESULTS: Ninety-nine patients affected by severe Protein- Energy
      Malnutritrion (PEM) due to AN were eligible in the study. Mean BMI was 12.5+/-0.9
      kg/m2, mean age 21.9+/-8.6 yrs. Of 99 patients, 75 (75.5%) completed the planned
      treatment (completer subgroup). Eighteen patients prematurely interrupted their
      treatment before achieving complete weight restoration (dropout subgroup); on
      average they were older and ill for a longer time before admission. Six patients
      asked to be transferred to other eating disorder units closer to their towns.
      Seventy-five completer AN patients continued to undergo intensive inpatient
      treatment till the achievement of BMI 18.3+/-0.8 kg/m2 and then they have been in
      follow-up outpatient for a mean period of 17.4+/-1.6 months with an average extra
      increase of their BMI until to 19.1+/-1.6 kg/m2. In 32 patients with a more
      severe malnutrition we had to resort to nasogastric enteral feeding for 4.4+/-2.5
      months, with a mean caloric supply of 1375+/-211 Kcal until the patients were no
      longer at life risk and they started to co-operate to treatment, increasing oral
      food amounts. DISCUSSION: Our results seem to provide strong support for using a
      highly structured program for treating patients with severe AN, including
      inpatient care and multidisciplinary medical and psychological teams specialized
      in eating disorder treatment.

PMID- 19169076
TI  - Somatic and psychological factors related to the body mass index of patients with
      anorexia nervosa.
AB  - OBJECTIVE: The aim of this study was to examine somatic and psychological factors
      related to the body mass index (BMI) of anorexia nervosa (AN) patients. METHOD:
      The analysis was of 24 hospitalized AN patients from the day after admission to
      the 4th day. The somatic factors analyzed were duration of AN, daily food intake,
      eating regulatory substances in blood (acylated ghrelin, desacyl ghrelin,
      leptin), serum cortisol, insulin and estimated creatinine clearance (CCr). The
      psychological factors analyzed were depression, anxiety, Eating Disorder
      Inventory (EDI), and hunger/fullness feeling. Measurement of BMI and collection
      of blood samples were done on the morning after hospitalization. Statistical
      analysis was by multiple linear regression analysis. RESULTS: BMI showed a
      reverse correlation with desacyl ghrelin (beta=-0.486, p=0.015) and maturity
      fears (beta=-0.375, p=0.046), but was not associated with any other factor by
      multiple regression analysis. CONCLUSION: The results suggest that desacyl
      ghrelin and maturity fears play important roles in the prolonged malnutrition
      state seen in AN patients.

PMID- 19169077
TI  - [How to identify rare allergens].

PMID- 19169078
TI  - [Impacts of environmental change on pollen allergens].

PMID- 19169079
TI  - [Practical aspects of patch testing (allergic reaction, irritable reaction, open
      test, closed patch test)].

PMID- 19169080
TI  - [Dendritic cells and allergy].

PMID- 19169081
TI  - [Infection and drug allergy].

PMID- 19169082
TI  - [Advocating the diagnostic criteria for early stage of asthma].
AB  - BACKGROUND: In asthmatic patients, first asthmatic symptoms are not often
      typical. In those cases, it takes long time before asthma diagnosis, and the
      severities are progressed in some patients. For early intervention, we tried to
      make the diagnostic criteria for asthma, which are useful to diagnose as early
      stage of asthma. METHODS: Three hundred and eighty eight of asthmatic patients,
      who were recorded first their symptoms in asthma, were enrolled. Their first
      symptoms and examinations were analyzed. RESULTS: In first asthmatic symptoms,
      79% of patients had cough, 68% patients had wheezing, 49% patients had dyspnoea,
      and 15% of patients did not have typical asthmatic symptoms in the early stage.
      The percentages of abnormal in first examinations were 99% in airway
      hypersensitivity, 92% of low %V25, 82% of eosinophila in sputum and 77% of low
      %V50. Low FEV1% and reversible airway obstruction were not seen in a lot of
      patients. CONCLUSION: We advocate that the diagnostic criteria for early stage of
      asthma are the following three elements. First criterion is spasmodic cough,
      wheezing and dyspnoea. Second criterion is airway hypersensitivity, or over 3% of
      eosinophils in sputum, or under 70% of %V50, or under 50% of %V25, or effect of
      bronchodilator. Effect of bronchodilator will be required, when the symptom is
      cough only. Third criterion is the exclusion of other lung and heart diseases.

PMID- 19169083
TI  - [Study of personal best value of peak expiratory flow in patients with asthma-
      comparison of the highest value of daily PEF under good control and the highest
      value of daily PEF obtained after using repeated inhaled beta2-agonist during
      high-dose inhaled steroid treatment].
AB  - BACKGROUND: In the guideline for asthma management, it is important to find the
      personal best value of peak expiratory flow (best PEF). Recently, we have
      substituted the highest value of PEF in daily life under good control (daily
      highest PEF) for the best PEF. AIM: In the present study, we considered whether
      the daily highest PEF could be used as the best PEF or not. METHOD: Subjects were
      30 asthmatics who were well controlled but whose baseline PEF values were less
      than 80 percent of predicted values. We compared the daily highest PEF and the
      highest of PEF obtained after repeated inhaled beta2-agonist (salbutamol MDI
      every 20 minutes three times). All subjects then received 1600 microg/day of
      beclomethasone dipropionate (BDP) for 4 to 8 weeks. We studied the effect of high
      dose inhaled steroid treatment on each PEF value and compared the daily highest
      PEF and the highest PEF obtained after using repeated salbutamol MDI during high
      dose inhaled steroid therapy on the examination day again. RESULT: The baseline
      PEF, daily highest PEF and the highest PEF obtained after salbutamol MDI were
      significantly less than the each values obtained after high-dose BDP. The best
      PEF value of them was the value obtained after repeated salbutamol MDI during
      high dose BDP. DISCUSSION: We suggest that the daily highest PEF under good
      control is not a substitute for best PEF because it changes according to the
      degree of improvement of airway inflammation. We recommend that a course of high
      dose inhaled steroid is effective in finding the best value of PEF for each
      individual with moderate asthma.

PMID- 19169084
TI  - [The effect of inhaled corticosteroid on the fraction of exhaled nitric oxide
      (FeNO) with off-line method in adult Japanese asthmatics].
AB  - BACKGROUND: The fraction of exhaled nitric oxide (FeNO) is a useful marker of
      asthma control. The FeNO measurement with our offline method using SIEVERS bag
      collection kit may be more affordable, but there have been no studies to show the
      effect of anti-asthmatic therapy on FeNO with our offline method. METHODS: The
      study population comprised 36 steroid-naive asthmatics at our outpatient clinic.
      We treated them according to asthma prevention and management guideline 2006,
      Japan. We also measured eNO levels by our offline method and spirometory on
      baseline, 4weeks, and 12 weeks of treatment. RESULTS: All asthmatics were symptom
      free on 12 weeks of treatment. The levels of FeNO FEV1/FVC were significantly
      decreased on 4 weeks and 12 weeks of treatment, compared with that on first
      visit. We classified the subjects into two groups; (A) FEV1/FVC <70% (n=11) or
      (B) FEV1/FVC > or =70% (n=25) on baseline. In (A) group, the level of FeNO and
      FEV1/FVC were significantly improved on 4 and 12 weeks of treatment. In (B)
      group, on 4 weeks of treatment, the level of FEV1/FVC was significantly increased
      but the level of FeNO was not significantly changed. On 12 weeks of treatment,
      the levels of FeNO was significantly decreased, but the level of FEV1/FVC was not
      significantly changed. CONCLUSION: The levels of FeNO were decreased by
      antiasthmatic therapy, so that offline monitoring of eNO will facilitate the
      management of bronchial asthma in patients treated with these drugs.

PMID- 19169085
TI  - [Development of quality of life assessment scale for caregivers of asthmatic
      children (QOLCA-24)].
AB  - PURPOSE: We developed the health related QOL questionnaire which is specific for
      a caregiver of an asthmatic child, who has been treated based on JPGL (Japanese
      Pediatric Guideline for the Treatment and Management of Asthma). METHOD: Based on
      the answers collected anonymously or with interviews concerning caregivers'
      quality of life influenced by having children with asthma, the multiple choice
      secondary questionnaire was made. Through psycho-analytic procedures of the data
      from secondary survey 24-item questionnaire (QOLCA-24) has been developed.
      RESULT: Factor analysis revealed 11 factor structure of QOLCA-24. Internal
      consistency (cronbach alpha) of whole 24 items was 0.942. kappa value which
      showed repetition plasticity was 0.27-0.53. The responsiveness associated with
      change of symptoms were significant in the items of factor 1 (Fear of asthma
      attack) and factor 7 (Job related burden of the caregiver). The score of most
      factors in QOLCA-24 were correlated with score of each item in SF-8. CONCLUSION:
      QOLCA-24 is thought to be useful as a tool to evaluate QOL of caregivers with
      asthmatic children.

PMID- 19169086
TI  - [Eosinophil chemotaxis assay using novel device EZ-TAXIScan].
AB  - BACKGROUND: Eosinophils are major effector cells in the pathogenesis of allergic
      inflammation such as bronchial asthma, and eosinophil migration to sites of
      inflammation is an important step. To date, several approaches have been
      developed to study eosinophil chemotaxis. Among them, the Boyden chamber method
      has been widely used, although this system requires a relatively large number of
      cells, and it usually provides no longitudinal information. In this study, we
      investigated real-time eosinophil chemotaxis using EZ-TAXIScan, a novel
      horizontal microchannel device. METHODS: Eosinophils were isolated from subjects
      with mild eosinophilia by modified CD16-negative selection. Eosinophil chemotaxis
      and migration speed induced by various chemoattractants including eotaxin,
      RANTES, PAF, and prostaglandin (PGD2) were measured by EZ-TAXIScan. We also
      determined the time course of chemotaxis using Boyden chambers. RESULT: By using
      EZ-TAXIScan, rapid (a few minutes after stimulation) and fast (20-30 microm/min)
      eosinophil chemotactic responses were observed by stimulation with PAF or PGD2,
      although eosinophils stimulated with eotaxin or RANTES showed relatively late (60
      minutes after stimulation) and slow (15 microm/min) responses. In contrast, using
      a Boyden Chamber, the chemotactic responses we tested showed a similar time
      course peaking at 20-60 min. CONCLUSION: The availability of EZ-TAXIScan for
      investigation of eosinophil chemotaxis was confirmed. However, it should be noted
      that EZ-TAXIScan showed a different response to certain chemoattractants compared
      with the conventional method.

PMID- 19169088
TI  - Interexaminer variance of median nerve compound muscle action potential
      measurements in hand position with and without fixation in plaster.
AB  - OBJECTIVES: We examined how hand fixation affects interexaminer variance in
      measuring compound muscle action potential (CMAP) during nerve conduction studies
      of the median nerve. METHODS: Subjects comprised 6 experienced examiners [1 woman
      and 5 men; mean (SD) age, 38.3 +/- 8.5 years; range, 28-46 years]. The
      standardized median nerve motor conduction setting was used for electromyography.
      The mean of 5 serial stimulations was taken as 1 examination for each subject.
      Distal latency, conduction velocity, and peak-to-peak amplitude of CMAP were
      measured as parameters. Subjects were examined without hand fixation and with
      hands fixed in prepared plaster molds. RESULTS: Fixation yielded significantly
      decreased coefficient of variance for CMAP amplitude (5.0% +/- 3.4%) compared
      with measurement without fixation (8.4% +/- 3.7%; P = 0.028). No differences in
      distal latencies or conduction velocities were evident between fixation and
      nonfixation. CONCLUSIONS: This study provides quantitative evidence for empirical
      observations that hand fixation might decrease CMAP variability in median nerve
      studies.

PMID- 19169089
TI  - Electrodiagnostic and clinical aspects of Guillain-Barre syndrome: an analysis of
      142 cases.
AB  - BACKGROUND: The incidence of Guillain-Barre syndrome (GBS) and its subtypes
      varies throughout the world. OBJECTIVE AND METHODS: We present a retrospective
      analysis of 142 GBS cases, treated at our center, aimed at classifying GBS
      electrophysiologically, to study the sequential electrophysiological changes in
      cases with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), and to
      look for any clinical and cerebrospinal fluid parameters that can also help in
      distinguishing the subtypes. RESULTS: One hundred twenty-one (85.2%) cases had
      AIDP, 15 (10.6%) had acute motor axonal neuropathy, and 6 (4.2%) were
      unclassifiable. CONCLUSIONS: Motor conduction blocks and temporal dispersion
      could be observed from days 3 and 5 onward, respectively. Progression of motor
      conduction slowing in AIDP was most impressive in the median nerves. Varying
      affection of deep tendon reflexes, cranial nerves, and cerebrospinal fluid
      albuminocytological dissociation can also help make a distinction between AIDP
      and acute motor axonal neuropathy. Sural sparing, a marker of demyelinating
      neuropathy, is more commonly seen in later than in early stages of AIDP.

PMID- 19169090
TI  - Safety of liquid intravenous immunoglobulin for neuroimmunologic disorders in the
      home setting: a retrospective analysis of 1085 infusions.
AB  - OBJECTIVE: To examine the overall safety of intravenous immunoglobulin (IVIG)
      administered according to a clinically defined, home-based therapeutic regimen in
      patients with neuroimmunologic diseases. METHODS: A total of 1,085 infusions of a
      new liquid IVIG 10% preparation were administered to 70 patients diagnosed with
      neuroimmunologic diseases over a 9-month period. These infusions were
      retrospectively reviewed for safety and tolerability. RESULTS: A very favorable
      adverse effect (AE) rate (4.7%) was calculated over a wide range of doses (0.9
      2.14 g/kg). There were no serious AEs reported, even among patients naive to IVIG
      therapy. Of 51 nonserious AEs, 53% occurred in 5 patients. CONCLUSIONS: The
      results of this review of 1,085 high-dose liquid IVIG infusions using a closely
      monitored, yet highly flexible, home-based therapeutic regimen indicate a very
      favorable tolerability profile in patients with neuroimmunologic disorders, even
      in those who were new to IVIG therapy.

PMID- 19169091
TI  - Diaphragm training in amyotrophic lateral sclerosis.
AB  - There is a continued need for therapies to improve respiratory function and
      quality of life in patients with amyotrophic lateral sclerosis. In this pilot
      trial, we studied 8 subjects with amyotrophic lateral sclerosis and respiratory
      involvement. We measured respiratory function and quality of life at baseline. We
      then taught subjects diaphragm training, a method of breath control designed to
      improve respiratory muscle strength and efficiency. We repeated measures of
      respiratory function and quality of life 6 and 12 weeks later. There was no
      significant improvement in any outcome measure after instituting diaphragm
      training. There was a nonsignificant trend toward a slower rate of decline in
      respiratory function in those subjects who mastered the technique; however, only
      half the subjects were able to successfully change their pattern of breathing. A
      larger study of this technique is warranted; however, in determining the sample
      size for a larger study, the difficulty for patients in mastering the technique
      must be taken into consideration.

PMID- 19169092
TI  - Peripheral nerve vasculitis presenting as complex regional pain syndrome.
AB  - OBJECTIVE: To report the clinical, electrodiagnostic, and pathologic findings in
      3 patients who presented with complex regional pain syndrome as their primary
      manifestation of peripheral nerve vasculitis. DESIGN: Case series. SETTING:
      Outpatient clinic in a tertiary care academic medical center. PATIENTS: Patient 1
      was a 39-year-old woman with a 9-year history of non-length-dependent severe
      burning pain and swelling in her extremities. Patient 2 was a 67-year-old man
      with a 2-year history of severe burning pain and swelling in an extremity after a
      fall. Patient 3 was a 74-year-old man with a 6-month history of severe allodynic
      pain and atrophy of the right hand after a viral illness RESULTS: In all 3 cases,
      clinical and electrodiagnostic testing were suggestive of multiple
      mononeuropathies. Nerve biopsy either confirmed vasculitis (patient 1) or was
      suggestive of angiopathy (patients 2 and 3). Immunomodulative therapy led to
      marked clinical improvement in all 3 cases. CONCLUSIONS: To our knowledge, this
      is the first report demonstrating that the inflammatory nerve injury seen with
      peripheral nerve vasculitis can result in complex regional pain syndrome.
      Clinical and electrodiagnostic assessments can help in the identification and
      management of these patients.

PMID- 19169093
TI  - Steroid-responsive paraneoplastic demyelinating neuropathy and myelopathy
      associated with breast carcinoma.
AB  - Paraneoplastic myeloneuropathy has rarely been reported with breast cancer. We
      report the case of a 59-year-old woman who presented with a peripheral neuropathy
      and cranial involvement and later developed a myelopathy. The neuropathy was
      found to be electrophysiologically and histologically demyelinating in nature.
      Magnetic resonance imaging studies failed to identify any structural brain or
      spinal cord abnormalities. The patient was diagnosed with breast carcinoma 4
      months after initial presentation and underwent resective surgery, radiotherapy,
      and hormonotherapy. Paraneoplastic antibodies (anti-Hu, anti-Yo, anti-Ri, anti
      CV2, anti-Ma, and anti-amphiphysin) were all negative. Her condition did not
      progress further after cancer treatment. Partial neurologic improvement occurred
      with oral steroid therapy, with subsequent deterioration on treatment withdrawal.

PMID- 19169095
TI  - Finasteride-induced myalgia and HyperCKemia.
AB  - BACKGROUND: Finasteride is an antiandrogen, inhibits type II 5-alpha reductase
      (enzyme that converts testosterone to more potent form dihydrotestosterone), and
      is commonly used in the treatment of benign prostatic hyperplasia and male
      frontal baldness; however, it is not free from side effects, which include sexual
      dysfunction and, rarely, myopathy. We report a case of finasteride-associated
      myalgia and hyperCKemia and review similar cases reported in the literature. CASE
      REPORT: A 30-year-old man who had been taking finasteride 5 mg/d for 10 years to
      treat frontal baldness developed diffuse muscle aches associated with elevated
      creatine kinase level to 10,117 IU/L with neither weakness nor pigmenturia. His
      symptoms resolved and his creatine kinase level dropped down to 256 IU/L 3 weeks
      after finasteride discontinuation. CONCLUSION: Reversible myalgia associated with
      significant hyperCKemia is a possible adverse reaction of finasteride therapy.

PMID- 19169096
TI  - Neuromuscular pathology case.

PMID- 19169097
TI  - Dysferlinopathy: from gene to protein.

PMID- 19169098
TI  - "When the iron men are all retired ... who will pin my hip?".

PMID- 19169099
TI  - The stress response to bilateral femoral fractures: a comparison of primary
      intramedullary nailing and external fixation.
AB  - OBJECTIVES: Concern has recently been expressed with regard to the physiologic
      effects of primary intramedullary femoral nailing in seriously injured patients.
      "Damage control orthopaedics" techniques have been proposed, which comprise
      principally the use of primary external fixation. The aim of this study was to
      compare the physiologic effects of external femoral fixation with those of
      intramedullary stabilization over the first 24 hours after femoral fracture using
      an established large animal (ovine) trauma model. METHODS: Under terminal
      anesthesia, bilateral high-energy femoral fractures and hypovolemic shock were
      produced using a pneumatic actuator. Twenty-four sheep were randomized into 4
      groups and monitored for 24 hours. Group 1--control, group 2--trauma only, group
      3--trauma and external fixation, and group 4--trauma and reamed intramedullary
      nailing. Outcome measures included the following: pulmonary embolic load
      (transesophageal echocardiography), metabolic base excess, plasma coagulation
      markers, and polymorphonuclear cell counts obtained from bronchoalveolar lavage
      samples. RESULTS: The total embolic load was significantly higher (P < 0.001) in
      the intramedullary nailing group. All trauma groups had a significant increase (P
      < 0.05) in prothrombin times with a fall in antithrombin III and fibrinogen
      levels. However, the type of fracture stabilization used did not significantly
      affect any of the other outcome measurements. CONCLUSIONS: A higher pulmonary
      embolic load can be expected during early intramedullary femoral fracture
      stabilization compared with primary external fixation. However, the degree of
      stimulation to systemic coagulation and pulmonary inflammation by each type of
      surgery was comparable.

PMID- 19169101
TI  - Orthogonal pin construct versus parallel uniplanar pin constructs for pelvic
      external fixation: a biomechanical assessment of stiffness and strength.
AB  - OBJECTIVE: The purpose of this study is to compare the structural stiffness of an
      orthogonal pelvic external fixator pin construct with 2 different parallel
      external fixator pin constructs in a simulated bone model. HYPOTHESIS: An
      orthogonal pelvic external fixator pin construct would be significantly more
      stiff than a parallel pin construct when loaded in-plane under similar
      conditions. DESIGN: Thirty synthetic pelvic bone models were configured with
      orthogonal pins (group 1), parallel iliac crest pins (group 2), or parallel supra
      acetabular pins (group 3). Specimens were loaded either in-plane
      (flexion/extension moment) or out-of-plane (internal/external rotation moment) to
      assess construct stiffness. SETTING: Orthopaedic industry mechanical testing
      laboratory (Stryker Orthopedics, Mahwah, NJ). INTERVENTION: Single load cycle to
      failure with load application modified to assess stiffness both in-plane and out
      of-plane with the pin constructs. MAIN OUTCOME MEASURE: Pelvic external fixation
      pin construct stiffness. RESULTS: Stiffness for in-plane loading was 150.2 +/-
      51.2 N/mm for the orthogonal pin construct, 105.0 +/- 46.9 N/mm for the iliac
      crest pin construct, and 104.7 +/- 20.7 N/mm for the supra-acetabular pin
      construct. Pairwise comparisons demonstrated that the difference was significant
      (P < 0.05) between groups 1 and 2 and groups 1 and 3 but not between groups 2 and
      3. Stiffness for out-of-plane loading was 49.6 +/- 3.4 N/mm for the orthogonal
      pin construct, 53.9 +/- 3.5 N/mm for the iliac crest pin construct, and 100.6 +/-
      4.3 N/mm for the supra-acetabular pin construct, with significant differences (P
      < 0.05) between groups 1 and 3 and groups 2 and 3 but not between groups 1 and 2.
      CONCLUSION: An orthogonal pelvic external fixator pin construct produced a
      significantly stiffer construct for in-plane loading (flexion/extension moment)
      compared with either parallel pin construct; however, a parallel supra-acetabular
      pin construct was stiffer for out-of-plane loading.

PMID- 19169102
TI  - Elastic stable intramedullary nailing versus nonoperative treatment of displaced
      midshaft clavicular fractures-a randomized, controlled, clinical trial.
AB  - OBJECTIVE: To compare elastic stable intramedullary nailing (ESIN) with
      nonoperative treatment of fully displaced midshaft clavicular fractures in
      adults. DESIGN: The study was a randomized, controlled, clinical trial. SETTING:
      Level 1 trauma center. PATIENTS AND METHODS: Sixty patients between 18 and 65
      years of age participated and completed the study. They were randomized to either
      operative or nonoperative treatment with a 2-year follow-up. INTERVENTION: Thirty
      patients were treated with a simple shoulder sling and 30 patients with ESIN
      within 3 days after trauma. MAIN OUTCOME MEASUREMENT: Complications after
      operative and nonoperative treatments, Disabilities of the Arm, Shoulder and Hand
      (DASH) score and Constant Shoulder Score for outcome measurement, and clavicular
      shortening. RESULTS: Fracture union was achieved in all patients in the operative
      group, whereas nonunion was observed in 3 of 30 patients of the nonoperative
      group. Two symptomatic malunions required corrective osteotomy in the
      nonoperative group. Medial nail protrusion occurred in 7 cases in the operative
      group. Implant failure with revision surgery was necessary in 2 patients after an
      additional adequate trauma. DASH scores were lower in the operative group
      throughout the first 6 months and 2 years after trauma, with a significant
      difference during the first 18 weeks. Constant scores were significantly higher
      after 6 months and 2 years after intramedullary stabilization. Patients in the
      operative group showed a significant improvement of posttraumatic clavicular
      shortening; they were also more satisfied with cosmetic appearance and overall
      outcome. CONCLUSIONS: ESIN of displaced midshaft clavicular fractures resulted in
      a lower rate of nonunion and delayed union, a faster return to daily activities,
      and a better functional outcome. Clavicular shortening was significantly lower,
      and overall satisfaction was higher in the operative group.

PMID- 19169103
TI  - Locked plating of 3- and 4-part proximal humerus fractures in older patients: the
      effect of initial fracture pattern on outcome.
AB  - OBJECTIVES: The use of locked plates in repairing osteopenic 3- and 4-part
      proximal humerus fractures remains controversial. The purpose of this article was
      to report the outcomes of open reduction and internal fixation in low-energy
      proximal humerus fractures treated with locked plating in patients older than 55
      years and stratify risk of failure or complication based on initial radiographic
      features. DESIGN: Retrospective. SETTING: Level I Trauma Center. METHODS: Seventy
      patients older than 55 years undergoing locked plate fixation for Neer 3- or 4
      part proximal humerus fractures were studied retrospectively. All patients had
      standardized, true size digital radiographs of the injured and normal shoulder in
      the axillary, scapular Y, and 20-degree external rotation views with a minimum of
      18 months' clinical follow-up. Two groups were identified based on the initial
      direction of the humeral head deformity: varus or valgus impaction. There were no
      statistical differences between treatment groups with regard to age, sex, Neer
      classification, follow-up, or dislocation. Radiographic measurements included
      humeral head angulation, tuberosity displacement, and length of the intact
      metaphyseal segment. Clinical outcomes measured Constant scores (CS) using active
      range of motion at latest follow-up. RESULTS: Twenty-four patients with initial
      varus fracture patterns healed with an average of 16-degree varus head angulation
      and an overall CS of 63 at an average of 34 months' follow-up. Forty-six patients
      with initial valgus fracture patterns healed with an average of 6 degrees of
      varus angulation and an overall CS of 71 at an average of 37 months' follow-up (P
      < 0.01). Complications of avascular necrosis, humeral head perforation, loss of
      fixation, tuberosity displacement >5 mm, and varus subsidence >5 degrees were
      encountered in 19 of 24 (79%) in the varus group compared with 9 of 46 (19%) in
      the valgus group (P < 0.01). Final CSs for 3-part fractures were 65 versus 72 (P
      < 0.01) for varus and valgus groups, respectively, and 61 versus 69 (P = 0.19)
      for 4-part fractures. CONCLUSIONS: Neer 3- and 4-part proximal humeral fractures
      in older patients with initial varus angulation of the humeral head had a
      significantly worse clinical outcome and higher complication rate than similar
      fracture patterns with initial valgus angulation. Two factors had significant
      influence on final outcome in these fracture patterns: initial direction of the
      humeral head angulation and length of the intact metaphyseal segment attached to
      the articular fragment. The best clinical outcomes were obtained in valgus
      impacted fractures with a metaphyseal segment length of greater than 2 mm, and
      this was independent of Neer fracture type. Humeral head angulation had the
      greatest effect on final outcomes (P < 0.001), whereas metaphyseal segment length
      of less than 2 mm was predictive of developing avascular necrosis (P < 0.001).

PMID- 19169104
TI  - The recovery of elbow range of motion after treatment of supracondylar and
      lateral condylar fractures of the distal humerus in children.
AB  - OBJECTIVES: To investigate the time required for elbow range of motion (ROM)
      recovery after supracondylar and lateral condylar fractures in children and to
      analyze the relationship between the ROM recovery and the related factors.
      DESIGN: Retrospective study. SETTING: Tertiary pediatric orthopaedic care unit at
      a general hospital. PATIENTS/PARTICIPANTS: Forty-five children with distal
      humerus supracondylar fractures and 16 children with lateral condylar fractures
      were followed. Twenty-seven children with distal forearm fractures, which were
      immobilized with long arm casts, were used as a control group to study elbow
      flexion-extension recovery after immobilization without elbow fracture. MAIN
      OUTCOME MEASUREMENTS: Elbow ROM was measured with a goniometer in a series of
      follow-up visits after cast removal until 90% ROM of the uninjured side had been
      reached. Morrey's definition was used to define ROM required for functional
      activity of daily living. RESULTS: The supracondylar fracture group took 29.5,
      39.0, 6.1, and 11.0 days to achieve 90% ROM in extension, flexion, supination,
      and pronation directions. The lateral condylar fracture group needed 30.2, 35.6,
      2.3, and 8.9 days, respectively, in 4 directions. In the distal forearm fracture
      group, the elbow total flexion-extension angle required less than 2 weeks to
      reach a total arc of 135 degrees. The supination range was easier to recover than
      the pronation motion. The flexion recovered last among 4 directions in supra- and
      lateral condylar fractures. CONCLUSIONS: In the uncomplicated distal humerus
      supracondylar and lateral condylar fractures, it takes 5 weeks to restore
      original elbow ROM after removal of long arm cast without physical therapy. This
      information could be applied in the education material to caregivers of children
      with elbow injuries.

PMID- 19169105
TI  - Balloon kyphoplasty combined with posterior instrumentation for the treatment of
      burst fractures of the spine--1-year results.
AB  - OBJECTIVE: Clinical and radiologic follow-up of patients with osteoporosis with
      painful, traumatic A3-type vertebral compression fractures in the thoracic and
      lumbar spine. DESIGN: Prospective study over the period of 1 year. SETTING: Level
      I Trauma Center. PATIENTS AND INTERVENTION: Twenty-five patients with
      osteoporosis (14 women and 11 men) and painful, traumatic A3-type fractures were
      treated with Balloon Kyphoplasty in combination with a short-segment posterior
      fixation (using the Universal Spine System). Twenty-one patients returned for
      their 1-year follow-up visit. X-rays were taken preoperatively, postoperatively,
      and at 3, 6, and 12 months' follow-up to evaluate vertebral height and local Cobb
      angle. Pain was measured using the self-reporting Visual Analogue pain Scale
      (VAS). Disability was measured using the Oswestry Disability questionnaire (ODI).
      RESULTS: The mean pain score (VAS) improved significantly from pretreatment to
      posttreatment from 7.8 +/- 2.2 (5.6-10) to 4.9 +/- 2.1 (2.8-8.0) (P < 0.001). It
      improved further to 2.9 +/- 1.4 (2.1-4.3) at 3 months and increased slightly
      after 1 year (3.8 +/- 1.9) (1.9-4.7). Limitation of daily activities (ODI)
      improved significantly from 88% (78-100) to 35% (15-48) at 3 months (P < 0.05).
      Improvement was maintained at 1 year at 36.5% (10-42). At 1-year follow-up,
      maintenance of the height restoration and kyphotic deformity correction was
      found. CONCLUSIONS: Balloon Kyphoplasty in combination with short-segment
      posterior instrumentation in traumatic A3 vertebral fractures led to a
      significant reduction in pain and disability. The combination of both surgical
      techniques was able to restore and maintain vertebral body height and correction
      of angular deformity. This technique might offer important safety advantages over
      an invasive anterior-posterior approach.

PMID- 19169106
TI  - Minimally invasive plating of the distal tibia: do we really sacrifice saphenous
      vein and nerve? A cadaver study.
AB  - OBJECTIVE: To investigate the risk of saphenous nerve (SN) and great saphenous
      vein (GSV) injury during percutaneous screw placement of the 3.5/4.5 LCP Distal
      Tibial Metaphyseal Plate and the 3.5-mm LCP Medial Distal Tibia Plate with tab in
      distal tibias of cadaver extremities. METHODS: Thirty-one unpaired (1 fresh and
      30 formalin fixed) adult cadaveric lower extremity specimens were dissected.
      Using the principles of minimally invasive plating, a 3.5/4.5 LCP Distal Tibial
      Metaphyseal Plate was implanted in 16 extremities and a 3.5-mm LCP Medial Distal
      Tibia Plate with tab in the remaining 15 extremities. Injuries to or any
      evidences of direct contact with the SN or GSV were recorded. Additionally, the
      shortest distances of each hole to the main branches of these anatomic structures
      were measured. RESULTS: The risk of injury to the SN and GSV was higher in holes
      4, 5, and 6 when using the 3.5/4.5 LCP Distal Tibial Metaphyseal Plate and in
      holes 3, 5, and 8 when using the 3.5-mm LCP Medial Distal Tibia Plate.
      CONCLUSIONS: The SN and GSV are at high risk for injury during percutaneous screw
      placement of the 3.5/4.5 LCP Distal Tibial Metaphyseal Plate and the 3.5-mm LCP
      Medial Distal Tibia Plate at the distal tibia. Careful dissection in the stab
      incisions down the plate, atraumatic placement of the drill sleeves, and
      protection of the soft tissues during screw insertion might decrease the risk of
      injury to the SN and GSV.

PMID- 19169107
TI  - Predictors of moderate or severe pain 6 months after orthopaedic injury: a
      prospective cohort study.
AB  - OBJECTIVE: To determine predictors of moderate or severe pain 6 months after
      orthopaedic injury. DESIGN: Prospective cohort study. SETTING: Two adult level 1
      trauma centers in Victoria, Australia. PARTICIPANTS: A total of 1290 adults
      admitted with orthopaedic injuries and registered by the Victorian Orthopaedic
      Trauma Outcomes Registry. MAIN OUTCOME MEASURES: Participant self-reported pain
      and health status using an 11-point numerical rating scale and the 12-item Short
      Form health survey, respectively. RESULTS: The prevalence of moderate or severe
      pain was 48% [95% confidence interval (CI), 45-51] at discharge and 30% (95% CI,
      28-33) at 6 months postinjury. Failure to complete high school [adjusted odds
      ratio (AOR) 1.5 (95% CI, 1.1-1.9)], self-reported preinjury pain-related
      disability [AOR 1.8 (95% CI, 1.3-2.5)], eligibility for compensation [AOR 2.1
      (95% CI, 1.6-2.8)], and moderate or severe pain at discharge from the acute
      hospital [AOR 2.4 (95% CI, 1.8-3.1)] were found to be independent predictors of
      moderate or severe pain at 6 months postinjury. CONCLUSIONS: Moderate or severe
      pain is commonly reported 6 months after orthopaedic trauma. Pain intensity at
      discharge and the effects of a "no-fault" compensation system are potentially
      modifiable factors that might be addressed through intervention studies to reduce
      the burden of persistent pain after orthopaedic trauma.

PMID- 19169108
TI  - The use of a kickstand modification for the prevention of heel decubitus ulcers
      in trauma patients with lower extremity external fixation.
AB  - External fixation is frequently used to manage patients with lower extremity
      trauma. Excessive pressure from contact surfaces must be avoided to prevent added
      morbidity from heel ulcers. The purpose of this article is to present a simple
      solution to off-load the heel by adding a "kickstand" to the external fixator.
      The kickstand modification is designed to prevent breakdown of the soft tissue
      covering of the heel that can complicate the treatment of the initial injury and
      may also result in calcaneal osteomyelitis. By preventing such damage, the
      kickstand modification may also help to avoid radical procedures for soft tissue
      coverage, prolonged treatment times, and, ultimately, amputations. The kickstand
      device is made by adapting 2 extra rods and clamps to the primary external
      fixator to obtain proper clearance of the heel when the foot is resting over a
      surface. In cases where traditional off-loading devices are difficult to apply
      and can interfere with proper wound care, the kickstand might provide a useful
      preventive solution. From January to August 2006, we applied this technique in 10
      patients with lower extremity trauma (11 fractures) and have seen no heel ulcers
      or other complications as per the staging system from the National Pressure Ulcer
      Advisory Panel.

PMID- 19169109
TI  - Use of a midline anterior incision for isolated medial tibial plateau fractures.
AB  - A technique using an anterior midline incision with a medial parapatellar
      arthrotomy and a medial full-thickness skin flap for the open reduction and
      internal fixation of isolated medial tibial plateau fractures is presented. The
      approach is advocated as an alternative to a posteromedial approach when medial
      tibial plateau fractures are present alone. The anterior approach is simple and
      familiar for orthopaedic surgeons. It offers good visualization, simplifies
      reduction, and provides a functional scar if future procedures are necessary.

PMID- 19169110
TI  - Orthopaedic injuries associated with fall from floor forty-seven.
AB  - This case report provides background reviewing mortality rates associated with
      falls from height before detailing the clinical history of a patient who survived
      a fall from a height of 43 stories. A multidisciplinary team treated both
      orthopaedic and nonorthopaedic injuries with the ultimate goal of preserving
      potential for independent function. A discussion of relevant pathoanatomy seen
      after falls from a height is included, and the discussion concludes with a review
      of damage control orthopaedics.

PMID- 19169111
TI  - Management of an unstable pelvic ring disruption in a 20-month-old patient.
AB  - A 20-month-old patient with a markedly displaced pelvic ring disruption was
      successfully managed with fluid resuscitation, immobilization using bolsters, and
      percutaneous screw fixation of the posterior ring coupled with hip spica casting.

PMID- 19169112
TI  - Who you are and where you live: race and the geography of healthcare.

PMID- 19169113
TI  - Ethnic differences in in-hospital place of death among older adults in
      California: effects of individual and contextual characteristics and medical
      resource supply.
AB  - BACKGROUND: : Substantial ethnic differences have been reported in the
      probability that death will occur in a hospital setting rather than at home, in a
      hospice, or in a nursing home. To date, no study has investigated the role of
      both individual characteristics and contextual characteristics, including local
      health care environments, to explain ethnic differentials in end-of-life care.
      OBJECTIVES: : The study purpose is to examine ethnic differences in the
      association between death as a hospital in-patient and individual and contextual
      characteristics, as well as medical resource supply. RESEARCH DESIGN: : This
      study employed a secondary data analysis. SUBJECTS: : We used data from the
      California Death Statistical Master file for the years 1999-2001, which included
      472,382 complete cases. These data were geocoded and linked to data from the US
      Census Bureau and the American Hospital Association. RESULTS: : Death as an in
      patient was most common for Asian (54%) and Hispanic immigrants (49%) and least
      common for non-Hispanic whites (36%) and US-born Asians (41%). Medical resource
      supply variables are of considerable importance in accounting for ethnic
      differentials in the probability of dying in a hospital. Residual differences in
      in-hospital site of death were largest for immigrant populations. CONCLUSIONS: :
      There are sizeable ethnic differentials in the probability that a death will
      occur in a hospital in California. These differences are substantially mediated
      by sociodemographic characteristics of the decedent and local medical care
      supply. One implication of these findings is that variation exists in the
      efficiency and quality of end of life care delivered to ethnic minorities.

PMID- 19169114
TI  - The pivotal impact of center characteristics on survival of candidates listed for
      deceased donor kidney transplantation.
AB  - BACKGROUND: There are currently over half a million end-stage renal disease
      patients and >70,000 patients listed to receive a deceased donor kidney
      transplant in the United States. To receive a deceased donor transplant, patients
      are placed on a waiting list at one of approximately 240 centers. Although
      candidate decisions to list at a particular center may often be made passively
      (based on proximity or physician referral), the important question remains as to
      whether the center of listing has a significant impact on patient outcomes.
      METHODS: The study evaluated adult kidney transplant candidates in the United
      States listed from 1995 to 2000 (n = 108,928) with follow-up through 2006. The
      primary outcome of patient survival was investigated with survival models
      evaluated with respect to 4 center characteristics (volume, donor quality,
      waiting time, past performance). Center characteristics derived from years
      preceding listing, simulating information that could be attainable for
      prospective candidates. RESULTS: Center waiting time had a marked association
      with survival (Adjusted hazard ratio = 1.32, 95% confidence interval: 1.27-1.38
      for the longest waiting times). Past performance and donor quality also had
      significant association with survival; center volume was not a significant
      factor. The cumulative impact of center factors resulted in an average 4-year
      difference in life expectancy. Center characteristics at listing were strongly
      correlated with levels at the time of transplantation and centers with the "best"
      characteristics were located in every region of the country. CONCLUSIONS: Center
      characteristics have significant impact on kidney transplant candidate survival.
      Information regarding the variability and importance of center factors should be
      clearly disseminated to transplant candidates.

PMID- 19169115
TI  - The Indiana Chronic Disease Management Program's impact on medicaid claims: a
      longitudinal, statewide evaluation.
AB  - BACKGROUND: : Disease management programs have grown in popularity over the past
      decade as a strategy to curb escalating healthcare costs for persons with chronic
      diseases. OBJECTIVES: : To evaluate the effect of the Indiana Chronic Disease
      Management Program (ICDMP) on the longitudinal changes in Medicaid claims
      statewide. RESEARCH DESIGN: : Phased implementation of a chronic disease
      management program in 3 regions of the state. Fourteen repeated cohorts of
      Medicaid members were drawn over a period of 3.5 years and the trends in claims
      were evaluated using a repeated measures model. SUBJECTS: : A total of 44,218
      Medicaid members with diabetes and/or congestive heart failure in 3 geographic
      regions in Indiana. RESULTS: : Across all 3 regions and both disease classes, we
      found a flattening of cost trends between the pre- and post-ICDMP-initiation
      periods. This change in the slopes was significant for all of the models except
      for congestive heart failure in southern Indiana. Thus, the average per member
      claims paid was increasing at a faster rate before ICDMP but slowed once the
      program was initiated. To distinguish shorter and longer-term effects related to
      ICDMP, we estimated annual slopes within the pre- and post-ICDMP- time periods. A
      similar pattern was found in all regions: claims were increasing before ICDMP,
      flattened in the years around program initiation, and remained flat in the final
      year of follow-up. CONCLUSIONS: : This analysis shows that the trend in average
      total claims changed significantly after the implementation of ICDMP, with a
      decline in the rate of increase in claims paid observed for targeted Medicaid
      program populations across the state of Indiana.

PMID- 19169117
TI  - Estimating Domestic Values for EQ-5D Health States Using Survey Data From
      External Sources.
AB  - BACKGROUND: Health status measures used to quantify outcomes for economic
      evaluation must be capable of representing health gain in a single index, usually
      calibrated in terms of the social preferences elicited from "the relevant
      population." The general problem faced in the majority of countries where social
      preferences are required for cost-effectiveness analysis is the absence of a
      value set based on domestic data sources. OBJECTIVES: This article establishes a
      methodology for estimating domestic visual analog scale (VAS)-based values for EQ
      5D health states by adjusting data sets from countries where valuation studies
      have been carried out. RESEARCH DESIGN: building upon the relationship between
      the values for respondents' real health states and hypothetical health states, 2
      models are investigated. One assumes that the link between VAS scores for real
      and hypothetical health state is constant across 2 countries (R1), whereas the
      other adopts the assumption that the relationship of VAS scores for hypothetical
      heath states between 2 countries functionally corresponds to variation in scores
      for real health states (R2). Data from national UK and US population surveys were
      selected to test both methods. RESULTS: The R2 model performed better in
      generating estimated scores that were closer to observed values. CONCLUSIONS: The
      R2 model seems to offer a viable method for estimating domestic values of health.
      Such a method could help to bridge the gap between countries as well as region
      within a country.

PMID- 19169116
TI  - Correlates of use of health care services by children and adolescents from 11
      European countries.
AB  - OBJECTIVE: To examine the association between use of health care services and
      health status, sociodemographic, and health care system characteristics in
      children and adolescents from 11 European countries. RESEARCH DESIGN: Cross
      sectional surveys in representative samples included using phone or school-based
      sampling. SUBJECTS: Children and adolescents aged 8-18 years and their parents.
      Questionnaires were administered in households or at schools in Austria, Czech
      Republic, France, Germany, Greece, Hungary, Poland, Spain, Switzerland, the
      Netherlands, and the United Kingdom. MAIN OUTCOME MEASURES: Any visit to
      ("access") and number of visits ("intensity of use") to health care professionals
      during the previous 12 months. RESULTS: The study included 16,210 parent-child
      pairs. In a multivariate analysis, variables statistically associated with access
      included the following: health status (more disability days, more chronic
      conditions), sociodemographic characteristics (being younger, being female,
      having a higher socioeconomic status, or higher parental educational level), and
      health system variables (higher percentage of public health expenditure,
      widespread private health care coverage, pediatrician-led system). The strongest
      association was with disability days [odds ratio (OR) = 6.92; 95% confidence
      interval (CI) = 5.24-9.14 for 5-15 days]. In the "intensity of use" model,
      sociodemographic (being younger, strong social support) and health status
      (chronic conditions, disability days, psychiatric disorders, psychosomatic
      complaints, poor health-related quality of life) characteristics were associated
      with greater intensity of use. Health system variables were not significant in
      this model. CONCLUSIONS: The likelihood of contacting the health services is a
      function of health status, socioeconomic factors, and health system
      characteristics. Intensity of use among those having made contact is associated
      with health status and sociodemographic characteristics but not with health
      system characteristics.

PMID- 19169118
TI  - Proxy assessment of health-related quality of life in african american and white
      respondents with prostate cancer: perspective matters.
AB  - OBJECTIVES: An emerging issue in the proxy literature is whether specifying
      different proxy viewpoints contributes to different health-related quality of
      life (HRQL) assessments, and if so, how might each perspective be informative in
      medical decision making. The aims of this study were to determine if informal
      caregiver assessments of patients with prostate cancer differed when prompted
      from both the patient perspective (proxy-patient) and their own viewpoint (proxy
      proxy), and to identify factors associated with differences in proxy perspectives
      (ie, the intraproxy gap). RESEARCH DESIGN AND METHODS: Using a cross-sectional
      design, prostate cancer patients and their informal caregivers were recruited
      from urology clinics in the Jesse Brown Veterans Affairs Healthcare System in
      Chicago. Dyads assessed HRQL using the EQ-5D visual analog scale (VAS) and EORTC
      QLQ-C30. RESULTS: Of 87 dyads, most caregivers were female (83%) and were
      spouses/partners (58%). Mean difference scores between proxy-patient and proxy
      proxy perspectives were statistically significant for QLQ-C30 physical and
      emotional functioning, and VAS (all P < 0.05), with the proxy-patient perspective
      closer to patient self-report. Emotional functioning had the largest difference,
      mean 6.0 (SD 12.8), an effect size = 0.47. Factors weakly correlated with the
      intraproxy gap included relationship (spouse) and proxy gender for role
      functioning, and health literacy (limited/functional) for physical functioning
      (all P < 0.05, 0.20 < r < 0.35). CONCLUSIONS: Meaningful differences between
      proxy-patient and proxy-proxy perspectives on mental health were consistent with
      a conceptual framework for understanding proxy perspectives. Prompting different
      proxy viewpoints on patient health could help clinicians identify patients who
      may benefit from clinical intervention.

PMID- 19169119
TI  - Measuring use and cost of care for patients with mood disorders: the utilization
      and cost inventory.
AB  - BACKGROUND: Researchers conducting cost-outcome studies must account for all
      materially relevant care that subjects receive from their care providers.
      However, access to provider records is often limited. This article describes and
      tests the Utilization and Cost Inventory (UAC-I), a structured patient interview
      designed to measure costs of care when access to provider records is limited.
      METHODS: UAC-I was tested on 212 consenting adult veterans with mood disorder
      attending a VA medical center. Counts (inpatient days and outpatient encounters)
      and costs (dollars) computed from survey responses were compared with estimates
      from medical records and an alternative structured questionnaire. RESULTS: The
      agreement between inpatient costs computed from provider records and from UAC-I
      responses, assessed using the intraclass correlation coefficient (ICC), was 0.66,
      95% confidence interval (CI), 0.30-0.84; the bias was -3.7%, 95% CI, -48 to 41.
      The ICC for the service data (inpatient days) was 0.97, 95% CI, 0.95-0.99; the
      bias was <1%, 95% CI, -14 to 15. The ICC for outpatient costs computed from
      provider records and from UAC-I responses was 0.53 95% CI, 0.38-0.65; the bias
      was <1%, 95% CI, -27 to 27. The ICC for outpatient encounters was 0.74, 95% CI,
      0.65-0.80; the bias was <1%, 95% CI, -16 to 18. CONCLUSIONS: These results
      indicate that it may be feasible for cost-outcome studies to compare patient
      groups for inpatient and outpatient costs computed from patient self-reports.

PMID- 19169120
TI  - Predictors of nursing home admission for persons with dementia.
AB  - OBJECTIVE: The objective of this systematic review was to identify factors that
      consistently predict nursing home admission (NHA) in persons with dementia.
      METHODS: Studies published in English were retrieved by searching the MEDLINE
      (1966-2006), PSYCINFO (1950-2006), CINAHL (1982-2006), and Digital Dissertations
      (1950-2006) databases. Bibliographies of retrieved studies were also searched.
      Information on study characteristics and empirical results were extracted using a
      standardized protocol. RESULTS: Of 782 relevant studies identified 80 were
      selected for review based upon eligibility criteria. The most consistent
      predictors of NHA in persons with dementia included severity of cognitive
      impairment, Alzheimer disease diagnosis, basic activity of daily living
      dependencies, behavioral symptoms, and depression. Caregivers who indicated
      greater emotional stress, a desire to institutionalize the care recipient, and
      feelings of being "trapped" in care responsibilities were more likely to admit
      persons with dementia to nursing homes. Demographic variables, incontinence, and
      service use did not consistently predict NHA. CONCLUSIONS: Several results seemed
      to challenge conventional assumptions of what precipitates NHA among persons with
      dementia. Caregiver stressors in conjunction with care recipient characteristics
      are important to consider when assessing NHA risk. The findings emphasize the
      need to construct more complex models of institutionalization when designing risk
      measures to target interventions.

PMID- 19169121
TI  - Changes over time and disparities in schizophrenia treatment quality.
AB  - BACKGROUND: Schizophrenia medication and psychosocial treatment options have
      expanded since the Schizophrenia PORT was conducted. However, there also have
      been considerable changes in the delivery of mental health care in the public
      sector, as well as increasing state concerns about Medicaid cost containment.
      OBJECTIVES: To examine trends and patient characteristics associated with
      differences in schizophrenia medication and visit treatment quality in a Medicaid
      population. RESEARCH DESIGN: Observational study of claims data from July 1, 1996
      to June 30, 2001. SUBJECTS: Florida Medicaid enrollees diagnosed with
      schizophrenia (N = 23,619). MEASURES: We examined the likelihood of meeting any 1
      and all 4 of the following quality standards: (1) receiving antipsychotic
      medication, (2) antipsychotic continuity, (3) dosing consistent with PORT
      recommendations, and (4) mental health visit continuity. Separate models were fit
      for acute and maintenance phases of treatment. RESULTS: Approximately 18% of
      acute and 7% of maintenance phases met all 4 quality standards. Antipsychotic
      quality improved (largely driven by an increasingly likelihood of receiving any
      antipsychotic), while visit continuity declined. The greatest disparities were
      seen for persons with co-occurring substance use disorders and of black race.
      Quality differences were often phase specific and at times in opposite directions
      across treatment phases. CONCLUSIONS: The improvement in antipsychotic treatment
      quality is encouraging. However, visit continuity declined. This study highlights
      the importance of quality measurement that includes focus on different treatment
      modalities and phases of care, as well as for potentially vulnerable populations
      (such as persons with co-occurring substance use disorders and racial/ethnic
      minorities).

PMID- 19169122
TI  - Using electronic health records to measure physician performance for acute
      conditions in primary care: empirical evaluation of the community-acquired
      pneumonia clinical quality measure set.
AB  - BACKGROUND: Electronic health records (EHRs) have the potential to facilitate
      performance measurement for acute conditions. OBJECTIVE: To evaluate the
      reliability and feasibility-of-use of a performance measure set for community
      acquired pneumonia in an ambulatory EHR. DESIGN: Retrospective, cross-sectional
      electronic chart review. SETTING: Primary Care Clinics. PATIENTS: Adults with an
      administrative claims diagnosis of pneumonia during a 14-month period.
      MEASUREMENTS: Two reviewers independently examined data in the EHR to determine
      if (1) the encounter was a visit for acute pneumonia; (2) there was documentation
      for each of 12 performance measures; and (3) such information was in coded form.
      RESULTS: Of 688 encounters with a claim diagnosis of pneumonia, 210 (31%) were
      identified by either reviewer as a primary care acute pneumonia visit. The 2
      reviewers agreed that 198 encounters to 71 different clinicians were visits for
      acute pneumonia [kappa, 0.96; 95% confidence interval (CI), 0.93-0.98]. Measure
      performance ranged from 10% for providing location of care rationale to 91% for
      documenting blood pressure, averaging 52% across all 12 measures. Inter-rater
      reliability ranged from 0.66 (95% CI, 0.47-0.84) for providing a location of care
      rationale to 0.97 (95% CI, 0.91-1.0) for vital sign assessment. The proportion of
      data that was in coded form ranged from 0% for mental status, hydration status,
      chest x-ray performance, and location of care to 100% for medications and
      immunizations. CONCLUSIONS: Although EHRs offer potential advantages for
      performance measurement for acute conditions, accurate identification of
      pneumonia visits was challenging, performance generally appeared poor, and much
      of the data were not in coded form.

PMID- 19169123
TI  - Adherence to quality indicators and survival in patients with breast cancer.
AB  - BACKGROUND: International initiatives increasingly advocate physician adherence
      to clinical protocols that have been shown to improve outcomes, yet the process
      outcome relationship for adhering to breast cancer care protocol is unknown.
      OBJECTIVE: This study explores whether 100% adherence to a set of quality
      indicators applied to individuals with breast cancer is associated with better
      survival. RESEARCH DESIGN AND SUBJECTS: Ten quality indicators (4 diagnosis
      related and 6 treatment-related indicators) were used to measure the quality of
      care in 1378 breast cancer patients treated from 1995 to 2001. Adherence to each
      indicator was based on the number of procedures performed divided by the number
      of patients eligible for that procedure. The main analysis of adherence was
      dichotomous (ie, 100% adherence vs. <100% adherence). MEASURES: The outcome
      measures studied were 5-year overall survival and progression-free survival,
      calculated using the Kaplan-Meier method. The Cox's proportional hazard
      regression model was used for univariate and multivariate analyses. RESULTS: Most
      patients received care that demonstrated good adherence to the quality
      indicators. Multivariate analysis revealed that 100% adherence to entire set of
      quality indicators was significantly associated with better overall survival
      [hazard ratio (HR): 0.46; 95% confidence interval (CI): 0.33-0.63] and
      progression-free survival (HR 0.51; 95% CI, 0.39-0.67). One hundred percent
      adherence to treatment indicators alone was also associated with statistically
      significant improvements in overall and progression-free survivals. CONCLUSIONS:
      Our study strongly supports that 100% adherence to evidence supported quality-of
      care indicators is associated with better survival rates for breast cancer
      patients and should be a priority for practitioners.

PMID- 19169124
TI  - Empirically derived composite measures of surgical performance.
AB  - BACKGROUND: Individual quality measures have significant limitations for
      assessing surgical performance. Despite growing interest in composite measures,
      empirically-based methods for combining multiple domains of surgical quality are
      not well established. OBJECTIVE: To develop and validate a composite measure of
      surgical performance that best describes variation in hospital mortality rates
      and forecasts future performance. RESEARCH DESIGN: Using the national Medicare
      claims database, we identified all patients undergoing aortic valve replacement
      in 2000 to 2001 (n = 53,120). To serve as input variables, we identified hospital
      level predictors of mortality with aortic valve replacement, including hospital
      volume, complication rates, and mortality with other procedures. Hospital
      specific predicted mortality rates were then determined using Bayesian-derived
      modeling techniques and assessed against subsequent hospital mortality (2002
      2003). RESULTS: Our composite measure explained 78% of the variation in aortic
      valve replacement mortality rates (2000-2001). The most important input variables
      were hospital volume, mortality with aortic valve replacement, and mortality for
      other high-risk cardiac procedures. The composite measure forecasted 70% of
      future hospital-level variation in mortality rates (2002-2003), and was
      substantially better in this regard than individual measures. Hospitals scoring
      in the bottom quintile on the composite measure in 2000 to 2001 had 2-fold higher
      mortality rates in 2002 to 2003 than hospitals in the top quintile (adjusted odds
      ratio, 1.97; 95% CI, 1.73-2.23). CONCLUSIONS: Compared with individual surgical
      quality indicators, empirically derived composite measures are superior in
      explaining variation in hospital mortality rates and in forecasting future
      performance. Such measures could be useful for public reporting, value-based
      purchasing, or benchmarking for quality improvement purposes.

PMID- 19169125
TI  - Relationship between malpractice litigation pressure and rates of cesarean
      section and vaginal birth after cesarean section.
AB  - BACKGROUND: Since the 1990s, nationwide rates of vaginal birth after cesarean
      section (VBAC) have decreased sharply and rates of cesarean section have
      increased sharply. Both trends are consistent with clinical behavior aimed at
      reducing obstetricians' exposure to malpractice litigation. OBJECTIVE: To
      estimate the effects of malpractice pressure on rates of VBAC and cesarean
      section. RESEARCH DESIGN, SUBJECTS, MEASURES: We used state-level longitudinal
      mixed-effects regression models to examine data from the Natality Detail File on
      births in the United States (1991-2003). Malpractice pressure was measured by
      liability insurance premiums and tort reforms. Outcome measures were rates of
      VBAC, cesarean section, and primary cesarean section. RESULTS: Malpractice
      premiums were positively associated with rates of cesarean section (beta = 0.15,
      P = 0.02) and primary cesarean section (beta = 0.16, P = 0.009), and negatively
      associated with VBAC rates (beta = -0.35, P = 0.01). These estimates imply that a
      $10,000 decrease in premiums for obstetrician-gynecologists would be associated
      with an increase of 0.35 percentage points (1.45%) in the VBAC rate and decreases
      of 0.15 and 0.16 percentage points (0.7% and 1.18%) in the rates of cesarean
      section and primary cesarean section, respectively; this would correspond to
      approximately 1600 more VBACs, 6000 fewer cesarean sections, and 3600 fewer
      primary cesarean sections nationwide in 2003. Two types of tort reform-caps on
      noneconomic damages and pretrial screening panels-were associated with lower
      rates of cesarean section and higher rates of VBAC. CONCLUSIONS: The liability
      environment influences choice of delivery method in obstetrics. The effects are
      not large, but reduced litigation pressure would likely lead to decreases in the
      total number cesarean sections and total delivery costs.

PMID- 19169126
TI  - Assessing the relationship between language proficiency and asthma morbidity
      among inner-city asthmatics.
AB  - BACKGROUND: Patient-provider communication is essential for high-quality asthma
      care. The objective of this study was to assess the potential relationship of
      language barriers with outcomes of inner-city asthmatics. RESEARCH DESIGN: We
      interviewed a prospective cohort of 318 adults with persistent asthma receiving
      care at 2 large inner-city clinics. Patients were classified into 3 groups
      according to their English proficiency; non-Hispanics (all native English
      speakers), Hispanics proficient in English, and Hispanics with limited English
      proficiency. Data on asthma control (Asthma Control Questionnaire), resource
      utilization, and asthma-related quality of life (Asthma Quality of Life
      Questionnaire) were collected at 1 and 3 months of enrollment. Univariate and
      multiple regression analyses were used to compare asthma morbidity and quality of
      life according to the patients' level of English proficiency. RESULTS: Overall,
      44% of patients were non-Hispanics, 38% were Hispanics proficient in English, and
      18% were Hispanics with limited English proficiency. Unadjusted, stratified, and
      multivariate analyses showed a significant association between limited
      proficiency and poorer asthma control, increased resource utilization, and lower
      quality of life scores after controlling for potential confounders (P < 0.05 for
      all comparisons). Additionally, limited English proficiency was associated with
      increased worries about side effects or becoming addicted to inhaled
      corticosteroids, beliefs that asthma is an acute disease, decreased self
      efficacy, and lower adherence rates. CONCLUSIONS: Inner-city asthmatics with
      limited English proficiency have significantly poorer asthma control, higher
      rates of resource utilization, and a lower quality of life. Further research is
      necessary to understand the mechanisms underlying this association.

PMID- 19169127
TI  - Identifying potentially avoidable hospital admissions from canadian long-term
      care facilities.
AB  - BACKGROUND: The provision of preventive services and continuity of care are
      important aspects of long-term care (LTC). A proposed quality indicator of such
      care is the rate of hospitalizations due to ambulatory care sensitive conditions
      (ACSCs). As the ACSC approach to identifying potentially avoidable
      hospitalizations (PAH) was developed for younger community-dwelling adults in the
      United States, we sought to examine its applicability as a quality indicator for
      older institutionalized residents in Canada. METHODS: ACSCs were identified in a
      linked hospital-based LTC and acute care administrative database at the Institute
      for Clinical Evaluative Sciences in Ontario, Canada. An expert panel was then
      convened to assess the applicability of existing ACSCs to an older
      institutionalized population in Canada and to develop consensus-based revisions
      appropriate to this setting. The revised definition of PAH was then applied to
      the same linked database. RESULTS: The proportion of hospitalizations categorized
      as a PAH using the original ACSCs was 47% (4177 of 8885). The panel suggested the
      inclusion of 2 new conditions (septicemia and falls/fractures) coupled with the
      deletion of 4 of the original ACSCs (immunization-preventable conditions;
      nutritional deficiency; severe ear, nose and throat infections; tuberculosis)
      that were rare hospital diagnoses in this population. Using the revised
      definition, 55% of hospitalizations (4874) were identified as potentially
      avoidable. CONCLUSIONS: Changes to the original list of ACSCs led to more
      hospitalizations being categorized as potentially avoidable. Significant
      variation between LTC facilities and over time in our PAH indicator may identify
      areas for improvement in preventive services and continuity of care for LTC
      residents.

PMID- 19169128
TI  - Comparison of population health status in six european countries: results of a
      representative survey using the EQ-5D questionnaire.
AB  - BACKGROUND: The EQ-5D questionnaire is an instrument for describing and valuing
      health states. OBJECTIVES: To compare general population health status measured
      by the EQ-5D in 6 European countries. METHODS: In the European Study of the
      Epidemiology of Mental Disorders representative population samples in Belgium (n
      = 2411), France (n = 2892), Germany (n = 3552), Italy (n = 4709), the Netherlands
      (n = 2367), and Spain (n = 5473) completed the EQ-5D as part of personal computer
      based home interviews in 2001 to 2003. RESULTS: Of all respondents, 35.1%
      reported problems in one or more EQ-5D dimensions, most frequently
      pain/discomfort (28.5%), followed by mobility (13.6%), usual activities (10.5%),
      anxiety/depression (8.0%), and self-care (3.6%). Proportions of respondents
      reporting any problems differed significantly between countries, ranging from
      26.6% in Spain to 44.5% in France. Mean EQ VAS score was 77.1, ranging from 75.0
      in Spain to 82.0 in the Netherlands. After adjusting for sociodemographic
      variables, the proportion of respondents reporting problems in any of the EQ-5D
      dimensions was significantly higher in France and lower in Spain and Italy than
      the grand mean. Even after controlling for reported EQ-5D health states, mean EQ
      VAS scores were significantly higher in the Netherlands and lower in Spain than
      the grand mean. Age, female gender, low educational level, lack of paid
      employment, and low income were associated with more problems in most of the EQ
      5D dimensions and lower EQ VAS scores. CONCLUSIONS: Self-reported EQ-5D health
      status differed considerably between countries, calling for caution when making
      international comparisons of disease burden and health care effectiveness.

PMID- 19169131
TI  - Public insurance: better financial protection or different level of service
      utilization?: Response to Yu et al, October 2008 Medical Care.

PMID- 19169129
TI  - Assessing the impact of behavioral risk factors and known-groups validity of the
      SF-12 in a US Chinese immigrant population.
AB  - BACKGROUND: Health status measures are being used in increasingly diverse
      populations. However, there are no known studies to date that examine the SF-12
      in US Chinese populations. This study reports on the performance and validity of
      the SF-12 among Chinese immigrants residing in New York City, and evaluates the
      impact of multiple behavioral risk factors on physical and mental health status.
      METHODS: We used cross-sectional survey data from a multistage probability sample
      of 2537 Chinese adults. SF-12 scores were examined according to sociodemographic,
      cultural, and clinical characteristics. Regression analyses were used to examine
      associations between health status and co-occurring behavioral risk factors of
      smoking, risky drinking, physical inactivity, and overweight/obesity. RESULTS: SF
      12 scores were significantly lower among women, those with less education, lower
      incomes, and more health problems (P < 0.001). Older adults had worse physical
      but better mental health (P < 0.05). Individuals with 1, 2, 3, and 4 behavioral
      risk factors reported decreases of 1.91, 2.92, 4.86, and 9.21 points on the PCS
      12, respectively, in comparison with the reference group having zero risk factors
      (P < 0.01). Similar trends up to 2 co-occurring risks were observed with MCS-12
      scores (P < 0.01). CONCLUSIONS: The SF-12 exhibited known-groups validity in a US
      Chinese immigrant population. Co-occurring behavioral risk factors were
      associated with progressive declines in physical health, independent of
      sociodemographic and clinical characteristics traditionally associated with
      impairments in health status. Targeting patients with multiple risks for behavior
      change may be effective in improving health across diverse populations.

PMID- 19169132
TI  - Inner ear anomalies and conductive hearing loss in children with Apert syndrome:
      an overlooked otologic aspect.
AB  - OBJECTIVE: To identify the occurrence of inner ear structural anomalies and
      conductive hearing loss (CHL) in children with Apert syndrome. STUDY DESIGN:
      Retrospective review. SETTING: Pediatric tertiary referral center. PATIENTS:
      Twenty pediatric patients with Apert syndrome were found; all patients (38/40
      ears) had inner ear anomalies. INTERVENTION(S): Computerized tomography of the
      head/temporal bone, pure-tone (including air and bone conduction) audiometry, and
      tympanometry. MAIN OUTCOME MEASURE(S): Imaging demonstrating inner ear anomalies,
      including malformations of the cochlea, dilated vestibule, and/or semicircular
      canal; audiologic findings of air-bone gap(s). RESULTS: Hearing loss was found in
      90% of the patients with Apert syndrome, and 80% of them had CHL. Air-bone gaps
      were found at all frequencies, with larger gaps at low frequencies. Fifty percent
      (20/40) of the ears had better than 0 dB hearing level bone conduction thresholds
      at 250 and/or 500 Hz. Normal middle ear pressure and mobility were found in all
      ears with intact eardrum. Inner ear anomalies were found in all patients, and 90%
      of them had bilateral involvement. Most frequently observed inner ear anomalies
      were dilated vestibule, malformed lateral semicircular canal, and cochlear
      dysplasia. CONCLUSION: Children with Apert syndrome may present with significant
      CHL that cannot be explained by minor middle ear pathologies alone. This
      conductive loss may be, at least partially, attributed to the inner ear
      anomalies; however, these structural anomalies are usually not recognized in
      these patients. Failure to close air-bone gap after surgical intervention may
      raise the suspicion of inner ear anomalies, and computed tomographic scan of the
      temporal bone can provide definitive proof.

PMID- 19169133
TI  - Cholesteatoma secondary to temporal bone involvement by Langerhans cell
      histiocytosis: a complication amenable to curative surgery.
AB  - OBJECTIVES: To describe secondary acquired cholesteatoma in patients previously
      treated for Langerhans cell histiocytosis (LCH). To focus on misleading symptoms
      suggesting LCH relapse. PATIENTS: This study involved 3 patients aged 12, 20, and
      58 months whose conditions were diagnosed with LCH. All 3 had involvement of the
      mastoid and of the skin of the external ear canal (EAC) at diagnosis. They were
      treated with steroids and vinblastine. INTERVENTIONS: Serial computed tomographic
      (CT) scans and clinical follow-up. MAIN OUTCOME MEASURE: Exploratory surgery of
      the mastoid. RESULTS: Otorrhea recurred in all 3 patients at 24, 17, and 26
      months, respectively, with difficulties to clinically identify a hole in the
      posterior part of the EAC. The otorrhea was considered a sign of a new occurrence
      of LCH, leading to systemic chemotherapy in 2 cases. A CT scan showed a defect in
      the posterior wall of the EAC and suggested cholesteatomatous invasion of the
      mastoid (2 true cholesteatomas and 1 precholesteatomatous case).Surgery (canal
      wall up mastoidectomies) successfully removed the cholesteatoma (bilateral in 2
      cases) and reconstructed the bony defect using cartilage. Biopsies ruled out LCH
      recurrence. CONCLUSION: Secondary acquired cholesteatoma (through a bony defect
      of the EAC) may occur in patients previously treated for LCH. Recurrence of
      symptoms and bone destruction on CT may wrongly suggest LCH recurrence. Surgery
      allows removal of the cholesteatoma as well as EAC reconstruction and control
      biopsy.

PMID- 19169134
TI  - Lengthening temporalis myoplasty versus hypoglossal-facial nerve coaptation in
      the surgical rehabilitation of facial palsy: evaluation by medical and nonmedical
      juries and patient-assessed quality of life.
AB  - BACKGROUND: To compare the results of 2 techniques of facial rehabilitation,
      lengthening temporalis myoplasty and 2 types of hypoglossal-facial (XII-VII)
      coaptation as evaluated by medical and nonmedical teams and patient self
      assessment of quality of life (QOL). MATERIALS AND METHODS: Videos of 42
      consecutive patients with complete facial palsy who underwent surgery from 1998
      to 2005 were reviewed. Facial rehabilitation was by temporalis myoplasty (n = 10)
      or by XII-VII coaptation (n = 32) either end-to-end (n = 16) or end-to-side with
      a jump interpositional graft (n = 16). Evaluation was by (i) a medical jury using
      4 facial nerve grading systems and 3 other measurements for the face at rest and
      during voluntary and emotional motions, (ii) a nonmedical jury using the 3
      measures described above, and (iii) patient self-assessment of QOL by
      questionnaires. RESULTS: Whatever the grading systems used, the medical jury
      rated facial rehabilitation with XII-VII coaptation better than myoplasty. Scores
      did not differ between the 2 types of coaptation: synkinesis was severe with end
      to-end and almost absent with end-to-side coaptation. However, muscle tone was
      stronger in the end-to-end than end-to-side coaptation. The nonmedical jury
      considered that XII-VII coaptation, whatever the type, led to better results than
      myoplasty. Patients in all groups considered their QOL improved by surgery,
      whatever the format, with no significant differences between the groups.
      CONCLUSION: This study revealed XII-VII coaptation with better results than
      myoplasty. End-to-end coaptation should be restricted to patients with a strong
      emotional expression or those with a long-standing facial palsy because it
      provides a strong muscle tone but significant synkinesis.

PMID- 19169136
TI  - Intracranial metastatic melanoma presenting with bilateral hearing loss.

PMID- 19169135
TI  - Functional studies reveal new mechanisms for deafness caused by connexin
      mutations.
AB  - OBJECTIVE: Connexin26 (Cx26) and Cx30 are the major protein subunits forming gap
      junction (GJ) intercellular channels in the cochlea. Mutations in these 2 Cxs are
      the major cause of nonsyndromic early childhood deafness in humans. The
      underlying mechanism for cochlear abnormality is unclear. Here, we used targeted
      Cx30 gene deletion (Cx30-/-) mice to investigate molecular mechanisms responsible
      for Cx mutation-linked deafness. Our hypothesis is that specific loss of GJ
      mediated biochemical coupling in the cochlea is sufficient to cause deafness.
      STUDY DESIGN: We compared: (1) expression of major cochlear GJ protein subunits,
      Cx26 and Cx30; and (2) biochemical coupling among cochlear supporting cells in
      the cochleae of wild type and Cx30-/- mice. METHODS: Immunolabeling was used to
      examine the expression of the remaining Cx protein expression in the cochlea of
      Cx30-/- mice. We also used a fluorescent dye diffusion assay performed on a novel
      flattened cochlear preparation to examine GJ-mediated metabolite transfer among
      cochlear supporting cells. RESULTS: Estimation of the residual ionic conductance
      indicated that considerable intercellular ionic coupling remained in the cochlea
      of Cx30-/- mice. Direct measurement of GJ-mediated biochemical coupling showed
      that the transfer of metabolites among cochlear supporting cells in Cx30-/- mice
      was severely reduced. CONCLUSION: Our data support that deficiency in GJ-mediated
      biochemical coupling is sufficient to cause Cx mutation-linked deafness.

PMID- 19169138
TI  - Steep declines in population-level AIDS mortality following the introduction of
      antiretroviral therapy in Addis Ababa, Ethiopia.
AB  - OBJECTIVES: Assessments of population-level effects of antiretroviral therapy
      (ART) programmes in Africa are rare. We use data from burial sites to estimate
      trends in adult AIDS mortality and the mitigating effects of ART in Addis Ababa.
      ART has been available since 2003, and for free since 2005. METHODS: To
      substitute for deficient vital registration, we use surveillance of burials at
      all cemeteries. We present trends in all-cause mortality, and estimate AIDS
      mortality (ages 20-64 years) from lay reports of causes of death. These lay
      reports are first used as a diagnostic test for the true cause of death. As
      reference standard, we use the cause of death established via verbal autopsy
      interviews conducted in 2004. The positive predictive value and sensitivity are
      subsequently used as anchors to estimate the number of AIDS deaths for the period
      2001-2007. Estimates are compared with Spectrum projections. RESULTS: Between
      2001 and 2005, the number of AIDS deaths declined by 21.9 and 9.3% for men and
      women, respectively. Between 2005 and 2007, the number of AIDS deaths declined by
      38.2 for men and 42.9% for women. Compared with the expected number in the
      absence of ART, the reduction in AIDS deaths in 2007 is estimated to be between
      56.8 and 63.3%, depending on the coverage of the burial surveillance. CONCLUSION:
      Five years into the ART programme, adult AIDS mortality has been reduced by more
      than half. Following the free provision of ART in 2005, the decline accelerated
      and became more sex balanced. Substantial AIDS mortality, however, persists.

PMID- 19169139
TI  - Clinical course of classic Kaposi's sarcoma in HIV-negative patients treated with
      the HIV protease inhibitor indinavir.
AB  - HIV protease inhibitors have been shown to exert antiangiogenic and antitumor
      actions independently from their antiretroviral effect. Based on these studies,
      HIV-seronegative patients with classic Kaposi's sarcoma were treated with
      indinavir and followed for clinical evolution, drug pharmacokinetics and Kaposi's
      sarcoma biomarkers. A favorable clinical course was associated with high drug
      plasma levels, reduced production of basic fibroblast growth factor, lower
      numbers of circulating endothelial cells, and a decrease in antibody titers
      against human herpesvirus 8.

PMID- 19169140
TI  - HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who
      have sex with men.
AB  - OBJECTIVES: Suppressive herpes simplex virus (HSV) therapy can decrease plasma,
      cervical, and rectal HIV-1 levels in HIV-1/HSV-2 co-infected persons. We
      evaluated the effect of HSV-2 suppression on seminal HIV-1 levels. DESIGN: Twenty
      antiretroviral therapy (ART)-naive HIV-1/HSV-2 men who have sex with men (MSM) in
      Lima, Peru, with CD4 >200 cells/microl randomly received valacyclovir 500 mg
      twice daily or placebo for 8 weeks, then the alternative regimen for 8 weeks
      after a 2-week washout. Peripheral blood and semen specimens were collected
      weekly. Anogenital swab specimens for HSV DNA were self-collected daily and
      during clinic visits. METHODS: HIV-1 RNA was quantified in seminal and blood
      plasma by TaqMan real-time polymerase chain reaction (RT-PCR) or Roche Amplicor
      Monitor assays. HSV and seminal cytomegalovirus (CMV) were quantified by RT-PCR.
      Linear mixed models examined differences within participants by treatment arm.
      RESULTS: Median CD4 cell count of participants was 424 cells/microl. HIV-1 was
      detected in 71% of 231 semen specimens. HSV was detected from 29 and 4.4% of
      swabs on placebo and valacyclovir, respectively (P < 0.001). Valacyclovir
      significantly reduced the proportion of days with detectable seminal HIV-1 (63%
      during valacyclovir vs. 78% during placebo; P = 0.04). Seminal HIV-1 quantity was
      0.25 log10 copies/ml lower [95% confidence interval (CI) -0.40 to -0.10; P =
      0.001] during the valacyclovir arm compared with placebo, a 44% reduction. CD4
      cell count (P = 0.32) and seminal cellular CMV quantity (P = 0.68) did not
      predict seminal plasma HIV-1 level. CONCLUSIONS: Suppressive valacyclovir reduced
      seminal HIV-1 levels in HIV-1/HSV-2 co-infected MSM not receiving ART. The
      significance of this finding will be evaluated in a trial with HIV-1 transmission
      as the outcome.

PMID- 19169141
TI  - Transcriptional changes in blood after aerobic interval training in patients with
      the metabolic syndrome.
AB  - BACKGROUND: Regular physical activity has beneficial effects on the metabolic
      syndrome. Eleven metabolic syndrome patients performing 16 weeks of aerobic
      interval training, significantly reduced their risk of cardiovascular disease, in
      terms of improved VO2max, endothelial function, blood pressure, insulin
      signaling, and plasma lipid composition. The knowledge on underlying mechanism of
      exercise-induced improvements is sparse, and a broad spectrum of methods is
      needed to gain more insight. DESIGN: The aim was, for the first time, to
      determine whether transcriptional changes occur in blood cells of metabolic
      syndrome patients after participating in an exercise program. METHODS: Blood was
      collected in PAXgene and EDTA tubes before and after 16 weeks of exercise. RNA
      was extracted and run on microarrays. RESULTS: Eleven biological processes and
      molecular functions were upregulated after exercise, whereas seven were
      downregulated. Blood clotting, cell adhesion, and steroid metabolism were among
      the downregulated processes, whereas steroid hormone-mediated signaling was
      upregulated. Downregulated protein levels of arginase 1 and von Willebrand factor
      confirmed microarray results. CONCLUSION: Increased transcription of genes
      involved in steroid hormone-mediated signaling, decreased levels of arginase 1,
      and reduced transcription of genes involved in cell adhesion, and blood clotting
      are likely to be involved in exercise-induced improvements of endothelial
      function, and improved cardiovascular risk profile of metabolic syndrome
      patients. These findings have provided new insights on exercise-induced
      improvement of cardiovascular health.

PMID- 19169142
TI  - Psychosocial adjustment and life satisfaction until 5 years after severe brain
      damage.
AB  - The objectives of this study were to describe psychosocial adjustment and outcome
      over time for severely brain-injured patients and to find suitable outcome
      measures for clinical practice during the rehabilitation process and for
      individual rehabilitation planning after discharge from hospital. The methods
      include a descriptive, prospective, population-based study. The participants were
      assessed at 6 months and annually until 5 years after traumatic brain injury or
      nontraumatic subarachnoid haemorrhage. Inclusion criteria were age 16-65 years,
      severe traumatic brain injury or nontraumatic subarachnoid haemorrhage defined as
      Glasgow Coma Scale 8 or worse and need for neurointensive care for at least 5
      days. The main outcome measures were Head Injury Evaluation Chart, Glasgow
      Outcome Scale Extended (GOSE) and Life Satisfaction Questionnaire (LiSat)-11
      checklist. Change over time for the group and the individuals, as measured with
      the GOSE, was analyzed by a statistical method that is suitable for small
      datasets and takes into account the nonmetric properties of the data. Eighteen
      patients were included. Three died and one was excluded for the long-term follow
      up (n=14). The group had a good outcome with no participant remaining in a
      vegetative state, 93% (12 of 13) went home and 60% (six of 10) returned to work.
      Eighty percent (eight of 10) of participants rated 'life as a whole' as
      satisfactory 5 years after the injury. The change at group level was significant
      (GOSE) until 1 year after the injury. The GOSE and the LiSat-11 were most
      clinically useful as they were easy to use for the rater/participants.

PMID- 19169143
TI  - Comparison of 1.0 M gadobutrol and 0.5 M gadopentetate dimeglumine-enhanced
      magnetic resonance imaging in five hundred seventy-two patients with known or
      suspected liver lesions: results of a multicenter, double-blind, interindividual,
      randomized clinical phase-III trial.
AB  - OBJECTIVE: To evaluate the diagnostic efficacy (accuracy, sensitivity,
      specificity) of 1.0 M gadobutrol versus 0.5 M gadopentetate for the
      classification of lesions as either benign or malignant in patients with known or
      suspected liver lesions. METHODS AND MATERIALS: A multicenter, phase-III,
      randomized, interindividually controlled comparison study with blinded reader
      evaluation was performed to investigate the diagnostic efficacy of a bolus
      injection of 1.0 M gadobutrol compared with 0.5 M gadopentetate at a dose of 0.1
      mmol Gd/kg BW. The imaging protocol included a dynamic 3D-evaluation, static
      conventional, and fat saturated T1-weighted sequences. MR datasets were evaluated
      by 3 independent radiologists. The standard of reference was defined by an
      independent truth panel (radiologist or hepatologist). The safety evaluation
      included adverse events, vital signs, and physical examination. RESULTS: A total
      of 497 of 572 patients were eligible for the final efficacy analysis.
      Noninferiority of gadobutrol-enhanced magnetic resonance imaging (MRI) for the
      classification of liver lesions was demonstrated on the basis of diagnostic
      accuracy determined by the on-site investigators (-0.098, 0.021) as well as for
      the average reader of the blinded evaluation (-0.096, 0.014) (95% confidence
      interval), compared with the predefined standard of reference. Very similar
      increases in sensitivity (ranging from approximately 10% to approximately 55%)
      and specificity (ranging from approximately 1% to approximately 18%) compared
      with precontrast MRI were also observed for the 2 contrast agent groups, with
      maximum differences of 4%.Very similar, low rates of adverse events were recorded
      for each of the 2 groups. No clinically relevant changes in vital signs or the
      results of the physical examination were observed in any patient. CONCLUSION:
      This study documents evidence for the noninferiority of a single i.v. bolus
      injection of 1.0 M gadobutrol (0.1 mmol/kg body weight) to 0.5 M gadopentetate
      (0.1 mmol/kg body weight) in the diagnostic assessment of liver lesions with
      contrast-enhanced MRI. The known excellent safety profile of gadobutrol was
      confirmed in this clinical trial and is similar to that of gadopentetate.

PMID- 19169144
TI  - Biomimetic MRI contrast agent for imaging of inflammation in atherosclerotic
      plaque of ApoE-/- mice: a pilot study.
AB  - OBJECTIVE: Atherosclerosis involves an inflammatory process characterized by
      cellular and molecular responses. A slow-clearance blood-pool paramagnetic agent
      (CMD-A2-Gd-DOTA: P717) chemically modified to create a functionalized product (F
      P717) for targeting inflammation in vessel walls was evaluated in vivo in mice.
      METHODS AND RESULTS: Carboxylate and sulfate groups were grafted onto the
      macromolecular paramagnetic Gd-DOTA-dextran backbone. Products were also
      fluorescently labeled with rhodamine isothiocyanate. Pre- and postcontrast MRI
      was performed on a 2-Tesla magnet in ApoE-/- and control C57BL/6 mice after P717
      or F-P717 injection at a dose of 60 micromol Gd/kg. Axial T1-weighted images of
      the abdominal aorta were obtained using a 2D multislice spin-echo sequence. F
      P717 significantly enhanced the magnetic resonance imaging (MRI) signal in the
      abdominal aortic wall of ApoE-/- mice (>50% signal-to-noise ratio increase
      between 10 and 30 minutes), but not of control mice. P717 produced only moderate
      (<20%) MRI signal enhancement within the same time frame. The MRI data were
      correlated to histopathology. Immunofluorescence in ApoE-/- mice colocalized F
      P717 but not P717 with the inflammatory area revealed by P-selectin labeling.
      CONCLUSION: This study demonstrates the efficacy of F-P717 as a new molecular
      imaging agent for noninvasive in vivo MRI location of inflammatory vascular tree
      lesions in ApoE-/- mice.

PMID- 19169145
TI  - Cirrhotic patients with a transjugular intrahepatic portosystemic shunt
      undergoing major extrahepatic surgery.
AB  - BACKGROUND: A transjugular intrahepatic portosystemic shunt (TIPS) can
      potentially reduce the risk of perioperative complications in cirrhotic patients
      undergoing surgery but experience is limited. The aim of our study was to assess
      the clinical outcomes in consecutive cirrhotic patients with a patent TIPS
      undergoing major extrahepatic surgery. METHODS: Between July 1992 and January
      2007, 25 cirrhotic patients with a patent TIPS underwent abdominal or
      cardiothoracic surgery at a single center. Preoperative laboratory and clinical
      features and postoperative outcomes were reviewed. RESULTS: Mean subject age was
      49+/-12 years. The TIPS was placed at a median of 20 days before surgery (range,
      1 to 2338 d). In 19 patients, the TIPS had been previously placed for management
      of refractory ascites or bleeding varices whereas in 6 patients, the TIPS was
      specifically placed for portal decompression before planned surgery. The mean
      hepatic venous pressure gradient was significantly reduced from 19.6+/-5.5 to
      8.7+/-2.9 mm Hg post-TIPS (P<0.001). The mean preoperative Model for End Stage
      Liver Disease (MELD) score was 15+/-7.6 and Child-Turcotte-Pugh scores were A
      (8%), B (64%), and C (28%). Nineteen abdominal and 6 cardiothoracic surgeries
      were performed under emergent (32%) or urgent (24%) circumstances.
      Postoperatively, severe ascites developed in 29% and encephalopathy in 17%. The
      median postoperative intensive care unit and hospital stay were 1 day (range, 0
      to 26 d) and 7 days (0 to 32 d), respectively. During a median follow-up of 33
      months, actuarial 1-year patient survival was 74%. The 3 patients (12%) who died
      during their hospitalization all had MELD scores > or = 25 and required emergency
      surgery. CONCLUSIONS: Portal decompression via TIPS may allow selected cirrhotic
      patients to safely undergo major surgery with an acceptable rate of short-term
      morbidity and mortality.

PMID- 19169146
TI  - Propofol alone versus propofol in combination with meperidine for sedation during
      colonoscopy.
AB  - BACKGROUND: Despite the increasing popularity of propofol for sedation in
      colonoscopy, the optimal regimen is still controversial. Both propofol alone and
      propofol in combination with meperidine are frequently used during colonoscopy,
      but the impact of adding meperidine has not been evaluated. This study aimed to
      investigate if adding meperidine to propofol offers any advantage in terms of
      patient tolerance, recovery time, and postcolonoscopy discomforts. METHOD:
      Consecutive patients admitted to the physical checkup department of our hospital
      were randomized to receive either meperidine plus propofol (combination group,
      n=100) or propofol alone (propofol group, n=100) for sedated colonoscopy. The
      patients' tolerance and postcolonoscopy discomforts (pain, bloating, dizziness,
      and nausea/vomiting) were assessed with a 0-10 visual analog scale. The recovery
      times were assessed with 5-minute and 10-minute Aldrete scores. RESULTS: The dose
      of propofol was less in the combination group than the propofol group (129.80+/
      37.93 mg vs. 147.90+/-47.85, mean+/-SD, P=0.003). The endoscopists, anesthetists,
      and nurses all rated patients' tolerance in favor of the combination group than
      the propofol group (mean+/-SD, endoscopists, 9.17+/-1.23 vs. 8.49+/-1.60,
      P=0.001; anesthetists, 9.21+/-1.08 vs. 8.63+/-1.37, P=0.001; nurses, 9.18+/-1.34
      vs. 8.71+/-1.47, P=0.019, respectively). Patients in the combination group
      recovered earlier than the placebo group (5-min Aldrete scores: 9.48+/-1.09 vs.
      9.05+/-1.32, mean+/-SD, P=0.013; short intervals to speak: 4.29+/-4.05 min vs.
      6.30+/-5.22 min, P=0.003; and departure: 18.62+/-5.28 min vs. 20.28+/-5.68 min,
      P=0.034). There was also less abdominal bloating in the combination group after
      colonoscopy (1.23+/-1.79 vs. 2.19+/-2.12, mean+/-SD, P=0.004). Incidences of
      hypoxemia, hypotension, and overall satisfaction scores were comparable between
      the 2 groups. CONCLUSIONS: For sedated colonoscopy, propofol in combination with
      meperidine is better than propofol alone in improving patients' tolerance and
      recovery.

PMID- 19169147
TI  - Non-English speakers attend gastroenterology clinic appointments at higher rates
      than English speakers in a vulnerable patient population.
AB  - GOALS: We sought to identify factors associated with gastroenterology clinic
      attendance in an urban safety net healthcare system. BACKGROUND: Missed clinic
      appointments reduce the efficiency and availability of healthcare, but
      subspecialty clinic attendance among patients with established healthcare access
      has not been studied. STUDY: We performed an observational study using secondary
      data from administrative sources to study patients referred to, and scheduled for
      an appointment in, the adult gastroenterology clinic serving the safety net
      healthcare system of San Francisco, CA. Our dependent variable was whether
      subjects attended or missed a scheduled appointment. Analysis included
      multivariable logistic regression and classification tree analysis. A total of
      1833 patients were referred and scheduled for an appointment between May 2005 and
      August 2006. Prisoners were excluded. All patients had a primary care provider.
      RESULTS: Six hundred eighty-three patients (37.3%) missed their appointment; 1150
      patients (62.7%) attended. Language was highly associated with attendance in the
      logistic regression; non-English speakers were less likely than English speakers
      to miss an appointment [adjusted odds ratio 0.42 (0.28, 0.63) for Spanish, 0.56
      (0.38, 0.82) for Asian language, P<0.001]. Other factors were also associated
      with attendance, but classification tree analysis identified language to be the
      most highly associated variable. CONCLUSIONS: In an urban safety net healthcare
      population, among patients with established healthcare access and a scheduled
      gastroenterology clinic appointment, not speaking English was most strongly
      associated with higher attendance rates. Patient-related factors associated with
      not speaking English likely influence subspecialty clinic attendance rates, and
      these factors may differ from those affecting general healthcare access.

PMID- 19169148
TI  - Clinical spectrum of reflux esophagitis among 25,536 Koreans who underwent a
      health check-up: a nationwide multicenter prospective, endoscopy-based study.
AB  - BACKGROUND: Gastroesophageal reflux is a commonly encountered condition, but
      detailed data on reflux symptoms in Asian countries are lacking. GOALS: To
      evaluate the prevalence and to document the clinical spectrum of endoscopic
      reflux esophagitis (RE). STUDY: A total 25,536 subjects underwent an upper
      gastrointestinal endoscopic examination as part of a health check, and completed
      a gastroesophageal reflux questionnaire. Endoscopic findings classified according
      to the Los Angeles (LA) classification and the data from gastroesophageal reflux
      questionnaire were analyzed. RESULTS: On the basis of endoscopic findings, 2019
      subjects (7.91%) were found to have RE: 5.87% in LA-A; 1.84% in LA-B; 0.18% in LA
      C; and 0.02% in LA-D. Heartburn, acid regurgitation, chest pain, hoarseness,
      globus sensation, cough, and epigastric soreness were found to be associated with
      RE (P<0.05). Heartburn, acid regurgitation, and epigastric soreness were more
      frequent in LA-B than in LA-A (P<0.05). Epigastric soreness was most bothersome
      in LA-A and LA-B, and acid regurgitation was most bothersome in LA-C and LA-D
      (P<0.01). Heartburn, hoarseness, and globus sensation were more frequent in men
      with RE, and acid regurgitation was most common in women. CONCLUSIONS: The
      prevalence of RE was found to be 7.91% in Korea, and the profiles of reflux
      symptoms were found to depend on grade of RE and sex.

PMID- 19169150
TI  - Acetaminophen hepatotoxicity and acute liver failure.
AB  - Acetaminophen-induced hepatotoxicity is a common consequence of acetaminophen
      overdose and may lead to acute liver failure (ALF). Currently acetaminophen is
      the most common cause of ALF in both United States and United Kingdom, with a
      trend to increasing incidence in the United States. N-acetylcysteine is the most
      effective drug to prevent progression to liver failure with acetaminophen
      hepatotoxicity. Liver transplantation is the only definitive therapy that will
      significantly increase the chances of survival for advanced ALF. This
      communication reviews current information regarding causes and management of
      acetaminophen-induced hepatotoxicity and ALF.

PMID- 19169149
TI  - Microscopic colitis: an update.
AB  - Microscopic colitis (MC) causes chronic diarrhea, abdominal cramping, nausea, and
      weight loss. Colonic mucosa appears normal on endoscopy; however, biopsies show
      abnormalities such as intraepithelial lymphocytosis in lymphocytic colitis, and a
      thickened subepithelial collagen band in collagenous colitis. Epidemiologic data
      demonstrates that MC is a more common cause of diarrhea than previously shown.
      Although the etiology of this condition is unclear, certain well-defined risk
      factors exist. Recently there has been more research on the pathophysiology of
      MC, and studies on treatment have demonstrated budesonide to be most effective,
      although other treatments also hold promise.

PMID- 19169151
TI  - Waiting for miracles.

PMID- 19169152
TI  - A potential role for notch signaling in the pathogenesis and regulation of
      hemangiomas.
AB  - Hemangiomas are the most common benign tumor of infancy, yet its pathogenesis and
      the mechanisms governing proliferation and involution are not well understood. It
      is believed that hemangiomas arise out of clonal, abnormal hemangioma endothelial
      cells (HemECs). The underlying anomaly of the HemEC is not known, although
      studies have shown that vascular endothelial growth factor (VEGF) and VEGF
      signaling may influence HemECs. Moreover, there are numerous subtypes of
      hemangiomas, with differences in natural history, potential for morbidity, and
      prognosis, and little is known how this relates to HemEC. The Notch signaling
      pathway is a highly conserved pathway across species from worms to mammals. Notch
      signaling has been shown to play a role during embryogenesis in directing
      vascular patterning and development and arterial and venous cell fate
      determination. Postnatally, it has been implicated in tumor angiogenesis in
      multiple malignancies. Notch signaling triggers tumor angiogenesis at least in
      part to stimulation by VEGF, thus establishing that there is a cross talk between
      the VEGF and Notch pathways. Given the presence of VEGF and its receptors in
      hemangiomas and known VEGF-Notch cross talk in tumor angiogenesis, the authors
      hypothesize that Notch signaling may contribute to hemangioma proliferation and
      involution. Preliminary studies of resected hemangioma specimens by reverse
      transcription polymerase chain reaction (RT-PCR) show that all 4 Notch receptors
      and 2 Notch ligands, Jagged1 and Delta-like ligand 4, are expressed by
      hemangiomas. These findings support a role for Notch in hemangiomas, meriting
      further analysis of the functional relevance of Notch signaling in hemangiomas.

PMID- 19169153
TI  - Progenitor cells in infantile hemangioma.
AB  - Infantile hemangioma is a vascular tumor that occurs in 5% to 10% of infants of
      European descent. A hallmark of infantile hemangioma is its life cycle, which is
      divided into 3 stages. The proliferating phase spans in the first year of
      postnatal life and is characterized by cellular masses without a defined vascular
      architecture and nascent blood vessels with red blood cells evident within the
      lumenal space. The involuting phase begins at 1 year of age and continues for 3
      to 5 years. Proliferation slows or stops in this phase, and histologic
      examination shows that the blood vessel architecture becomes more obvious and
      vessel size is enlarged. The involuted phase reaches 5 to 8 years of age, at
      which point blood vessels are replaced with a fibrofatty residuum and capillary
      sized channels. The growth and involution life cycle of infantile hemangioma are
      very different from other vascular tumors and vascular malformations, which do
      not regress and can occur at any time during childhood or adult life. Many
      laboratories have reported on the endothelial characteristics of the cellular
      masses that are prominent in the proliferating phase of infantile hemangioma, as
      well as their immature appearance. These studies, along with isolation and
      characterization of hemangioma-derived cell populations with progenitor cell
      properties, have lead to an emerging hypothesis that hemangioma is caused by an
      abnormal or delayed differentiation of mesodermal progenitor cells into the
      disorganized mass of blood vessels. In this paper, we discuss the literature that
      supports this emerging hypothesis.

PMID- 19169154
TI  - Long-term results after using dynamic presurgical nasoalveolar remodeling
      technique in patients with unilateral and bilateral cleft lips and palates.
AB  - OBJECTIVE: To evaluate the effects and durability of results after using dynamic
      presurgical nasoalveolar remodeling in patients with unilateral and bilateral
      cleft lips and palates. METHOD: Dynamic presurgical nasoalveolar remodeling
      technique does not rely on the relatively static force exerted by the orthopedic
      plate held in place by means of tape or adhesives. The principle behind this
      procedure is the use of the force generated during suction and swallowing to
      produce the remodeling effects on the nasal structures. The nasal component acts
      not only on the nasal structures but also in the lip function by stimulating
      labial muscle contraction. Direct anthropometry performed before primary
      reconstruction of the lip and nose and 1 year later posterior to surgery suggests
      that results are permanent. CONCLUSIONS: When the dynamic presurgical
      nasoalveolar remodeling protocol is instituted early, it can avoid memory
      cartilage fixation. Changes incorporated to the nasal extension allowed us to
      obtain better results, elevating the nasal tip, remodeling the depressed cleft
      side alar cartilages in unilateral cases, and repositioning and correcting the
      positional alteration of the nasal cartilages building a new columella in
      bilateral cases. In addition, comfort and tolerance of patients has been
      improved, and adjustments needed during follow-up have been simplified,
      significantly reducing the consultation time and increasing the interval between
      appointments. The obtained outcome facilitates primary surgical cleft lip and
      nose reconstruction and improves surgical results.

PMID- 19169155
TI  - Mechanisms of osteoinduction/chondroinduction by demineralized bone.
AB  - Demineralized bone is widely used for osseous reconstructive procedures. Bone
      morphogenetic proteins (BMPs) have been studied as the putative active components
      of demineralized bone; recombinant BMPs are Food and Drug Administration-approved
      for use with scaffold carriers. An experimental three-dimensional in vitro model
      was developed to allow comparison of early changes in signaling and gene
      expression in cells exposed to demineralized bone particles (DBPs) or to BMP
      and/or transforming growth factor beta (TGF-beta). The culture device consists of
      a bilayer of porous collagen lattice that contains either a packet of DBPs or an
      insert of the dense collagen scaffold with BMP and/or TGF-beta. As expected, BMP
      and TGF-beta induced distinct signaling pathways and events in human dermal
      fibroblasts; DBPs signaled both pathways and their target genes. A mixture of BMP
      and TGF-beta stimulated the production of extracellular matrix chondroitin that
      approximated the composition that was stimulated by DBPs, but to a lesser amount.
      Although BMP was originally isolated as the active factor in DBPs, it does not
      show DBPs' effects on signaling and chondroinduction in vitro. Multiple members
      of the TGF-beta superfamily and other constituent factors may be involved in
      skeletal induction of human dermal fibroblasts by DBPs. This in vitro culture
      system may be useful to provide a rational basis for designing improved
      osteoinductive/chondroinductive materials.

PMID- 19169156
TI  - Palatoplasty outcomes in nonsyndromic patients with cleft palate: a 29-year
      assessment of one surgeon's experience.
AB  - The primary objective of cleft palate repair is velopharyngeal competence without
      fistula. The reported incidence of fistula and velopharyngeal insufficiency (VPI)
      is variable. Our purpose was to assess the senior surgeon's 29-year palatoplasty
      experience with respect to incidence of fistula and VPI. Our hypotheses were that
      VPI is related to (1) age at palatoplasty, (2) cleft palate type, and (3) VPI and
      palatal fistula incidence decrease with the surgeon's experience. We reviewed the
      records of all children with cleft palate treated by the senior author between
      1976 and 2004. Cleft palate was categorized according to Veau. Palatoplasty was
      performed on 449 patients, using a 2-flap technique with muscular
      retropositioning. The mean age at palatoplasty was 11.6 +/- 4.9 months (range,
      7.0-46.4 months). The incidence of palatal fistula was 2.9%, and velopharyngeal
      sufficiency was found in 85.1% of patients. We found a significant association
      between age at palatoplasty and VPI (P = 0.009, odds ratio, 1.06 [95% confidence
      interval, 1.02-1.10]). Velopharyngeal insufficiency was also associated with the
      Veau hierarchy (P = 0.001). Incidence of VPI was independent of surgeon
      experience (P = 0.2). In conclusion, the incidence of palatal fistula was low.
      Velopharyngeal insufficiency was associated with increasing age at palatoplasty
      and with the Veau hierarchy.

PMID- 19169157
TI  - Palatoplasty: suturing the mucoperiosteal flaps to the hard palate through hole.
AB  - We satisfactorily repaired a wide cleft palate using a method of V-Y pushback and
      anchoring the oral mucoperiosteal flap onto the bony ridge of the cleft. An 8
      year-old Vietnamese girl had a wide incomplete bilateral posterior cleft palate
      associated with congenital cardiac malformations. The gap of the posterior cleft
      was 2.5 cm, which exceeded the total widths of the palatal shelves. We applied V
      Y pushback and used a vomer flap to close the wide cleft palate. The posterior
      two thirds of the nasal mucosae from the cleft margins were sutured to the vomer
      flap. The nasal side of the anterior one third of the bony cleft was uncovered.
      The elevated bilateral mucoperiosteal flaps were brought together to the midline
      and sutured to the anterior triangular flap in a V-Y pushback fashion. Four holes
      were drilled 5 mm lateral to each bony cleft margin. The lateral sides of the
      mucoperiosteal flaps were fixed to the palate bone with 3-0 Vicryl through the
      hole. This method reduces the tension of the flap which might frequently cause
      oronasal fistula and also improve viability.

PMID- 19169158
TI  - Implant-supported distraction osteogenesis: a technique to advance the deficient
      maxilla.
AB  - We describe a technique in which osseointegrated implants are used as anchors to
      support a custom-fabricated distraction device to advance the deficient anterior
      maxilla. The absolute rigidity of osseointegrated implants in bone provides
      stable anchorage for successful distraction.

PMID- 19169159
TI  - Childhood bullying behaviors as a risk for suicide attempts and completed
      suicides: a population-based birth cohort study.
AB  - OBJECTIVE: There are no previous studies about the association of childhood
      bullying behavior with later suicide attempts and completed suicides among both
      sexes. The aim was to study associations between childhood bullying behaviors at
      age 8 years and suicide attempts and completed suicides up to age 25 years in a
      large representative population-based birth cohort. METHOD: The sample includes
      5,302 Finnish children born in 1981. Information about bullying was gathered at
      age 8 years from self-report, as well as parent and teacher reports. Information
      about suicide attempts requiring hospital admission and completed suicides was
      gathered from three different Finnish registries until the study participants
      were 25 years old. Regression analyses were conducted to determine whether
      children who experience childhood bullying behaviors are at risk for later
      suicide attempts and completed suicides after controlling for baseline conduct
      and depression symptoms. RESULTS: The association between bullying behavior at
      age 8 years and later suicide attempts and completed suicides varies by sex.
      Among boys, frequent bullying and victimization are associated with later suicide
      attempts and completed suicides but not after controlling for conduct and
      depression symptoms; frequent victimization among girls is associated with later
      suicide attempts and completed suicides, even after controlling for conduct and
      depression symptoms. CONCLUSIONS: When examining childhood bullying behavior as a
      risk factor for later suicide attempts and completed suicides, each sex has a
      different risk profile.

PMID- 19169160
TI  - Effective herbal treatment of vasomotor symptoms--are we any closer?

PMID- 19169161
TI  - Validation of self-reported history of hysterectomy and oophorectomy among women
      in an integrated group practice setting.
AB  - OBJECTIVE: Classification of menopause status often relies on self-report and is
      centrally important to research and clinical practice. This study was designed to
      assess the validity of self-reported hysterectomy and oophorectomy. METHODS: A
      validation study of self-reported surgical menopause was conducted using survey
      data and electronic medical records from women enrolled in the Breast Cancer
      Screening Program within an integrated group practice in Washington State.
      Sensitivity of self-reported surgical history was estimated from questionnaire
      data among women with a history of hysterectomy (n = 1,935) and/or oophorectomy
      (n = 1,010) per medical records. Positive predictive values were quantified by
      reviewing medical records for a subset of women who self-reported a hysterectomy
      and/or oophorectomy (n = 122). RESULTS: Women self-reported hysterectomy history
      with great accuracy (sensitivity, 91%; positive predictive value, 97%) but were
      less accurate in reporting oophorectomy history (sensitivity of bilateral
      oophorectomy, 64%; positive predictive value, 100% and 73% for bilateral and
      unilateral oophorectomy, respectively). Among women self-reporting a unilateral
      oophorectomy, 19% had had both ovaries removed. CONCLUSIONS: Self-report is a
      valid data collection tool for hysterectomy history, but care should be taken in
      querying for and interpreting self-reported oophorectomy history for determining
      menopause status.

PMID- 19169162
TI  - Attitudes of obstetrician-gynecologists toward the evidence from the Women's
      Health Initiative hormone therapy trials remain generally skeptical.
AB  - OBJECTIVE: To examine the opinions of obstetrician-gynecologists regarding
      hormone therapy (HT) and the results from the Women's Health Initiative (WHI).
      METHODS: Separate surveys were sent to two groups of practicing obstetrician
      gynecologists: (1) respondents to a 2004-2005 survey (follow-up 1) and (2)
      members of the American College of Obstetricians and Gynecologists' Collaborative
      Ambulatory Research Network (follow-up 2 CARN). These studies complete a
      longitudinal study investigating obstetrician-gynecologists' opinions of the
      evidence from WHI. RESULTS: Response rates were 64.5% and 58.8%, respectively.
      Responses from both surveys were generally consistent with the results from the
      2004-2005 survey. A majority of physicians from both survey populations were
      skeptical of the combined HT results. Respondents were more likely to find the
      results of the unopposed estrogen trial convincing. Similar to the results from
      the 2004-2005 study, CARN physicians generally disagreed with the decision to end
      the WHI trials. Unlike the 2004-2005 study, there was no consistent effect of
      either age or year that residency was completed on physician opinions. Similar to
      the 2004-2005 study, physicians who considered alternative therapies as viable
      treatment options were more likely to report that they found the trial results
      convincing. The results from follow-up 2 CARN indicate that physicians in the
      south were most likely and physicians in the east were least likely to prescribe
      HT, suggesting that unmeasured sociocultural parameters might influence HT
      prescribing practice. CONCLUSIONS: Obstetrician-gynecologists remain generally
      skeptical of the WHI results, although less so of the estrogen-only trial. The
      early end to the trials may have contributed to their skepticism.

PMID- 19169163
TI  - Osteoprotective effect of Phaseolus vulgaris L in ovariectomy-induced osteopenia
      in rats.
AB  - OBJECTIVE: Phytoestrogens and phytoestrogen-containing plants are currently being
      explored as potential candidates for the treatment of estrogen-related disorders.
      The aim of this study was to evaluate the anti-osteoporotic effect of the
      phytoestrogen-rich plant Phaseolus vulgaris L, commonly known as French beans.
      METHODS: Adult Sprague-Dawley rats were either bilaterally ovariectomized (OVX)
      or sham operated. OVX and sham control groups were administered vehicle, whereas
      the other two OVX groups were given 0.15 mg/kg estradiol and 1 g/kg methanolic
      extract of P vulgaris L seeds (MPV) orally for 10 weeks (10 rats per group). At
      autopsy, blood, urine, bones, and uteri of the animals were collected. Serum was
      evaluated for estradiol, calcium (Ca), phosphorus, alkaline phosphatase,
      tartarate resistant acid phosphatase, and urine for Ca. The bone density, ash
      density, mineral content, and mechanical strength of bones was evaluated.
      Scanning electron microscopic analysis of bones (tibia) was performed. Results
      were analyzed using analysis of variance and Tukey's multiple comparison test.
      RESULTS: Compared with the OVX control, MPV (1 g/kg PO) significantly decreased
      serum alkaline phosphatase and reduced serum tartarate resistant acid phosphatase
      and urinary Ca levels. It caused an increase in bone density, ash density, and
      bone mechanical strength and significantly increased bone Ca. Improvement in bone
      microarchitecture was indicated by image analysis of scanning electron
      microscopic photomicrographs. No increase in weight of atrophic uterus in OVX
      animals was observed with MPV treatment. CONCLUSIONS: Treatment with MPV
      prevented estrogen deficiency-induced osteopenia without affecting the uterine
      mass. The promising results of the study warrant further investigation of French
      beans as a potential candidate for the treatment of postmenopausal osteoporosis.

PMID- 19169165
TI  - Effects of menopause and hormone therapy on erythrocyte deformability.
AB  - OBJECTIVE: The climacteric disturbance seen among perimenopausal women often
      includes symptoms related to poor microcirculation. This hemorheological
      condition plays an important role in the hemodynamism of microcirculation.
      Specifically, erythrocyte deformability is considered to be one of the most
      significant factors in determining this hemorheological condition. METHODS: The
      present study investigated the level of erythrocyte deformability in four groups
      of women: namely, 10 healthy premenopausal women (PRE group), 25 postmenopausal
      women (POST group), 20 postmenopausal women on estrogen therapy (ET group) who
      received conjugated equine estrogens 0.625 mg/day, and 20 postmenopausal women on
      estrogen plus progestogen therapy (EPT group) who received conjugated equine
      estrogens 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day. The
      erythrocyte deformability score (EDS), measured by the Micro Channel Array Flow
      Analyzer, was determined as an index of erythrocyte deformability. RESULTS: The
      mean EDS for the POST group was significantly higher (mean +/- SE, 1.02 +/- 0.04)
      (P < 0.01) than that for the PRE group (0.78 +/- 0.05). The mean EDS for the ET
      group (0.88 +/- 0.03) was significantly lower than that for the POST group and
      close to that of the PRE group. There was no difference in the EDS values between
      the ET group and the EPT group (0.87 +/- 0.03). CONCLUSIONS: These results
      indicate that erythrocyte deformability may worsen with the decrease in the
      estrogen level because of the onset of menopause, and also suggest that ET and
      EPT may allow it to recover.

PMID- 19169164
TI  - A prospective study of the association between endogenous hormones and depressive
      symptoms in postmenopausal women.
AB  - OBJECTIVE: Across a woman's lifetime, variations in hormone levels are known to
      influence mood and well-being. Whether absolute or changes in hormone levels over
      time are associated with depression among postmenopausal women remains unclear.
      METHODS: The Melbourne Women's Midlife Health Project is a longitudinal
      population-based study of women who were followed through the menopausal
      transition. This analysis is based on data collected from 138 postmenopausal
      women in years 11 and 13 of the study, who were assessed for the presence of
      depressive symptoms using the Center for Epidemiological Studies Depression
      Scale. Logistic regression models were developed to determine whether absolute or
      changes in hormone levels were associated with depression. RESULTS: No
      significant associations were found between depressive symptoms and the absolute
      levels of sex hormone-binding globulin, testosterone, free androgen index,
      estradiol, free estradiol, or follicle-stimulating hormone (FSH). On the other
      hand, women with a decline in total serum estradiol over the 2-year period had a
      more than threefold increased risk of depressive symptoms (odds ratio, 3.5; 95%
      CI, 1.2-9.9). A large increase in FSH levels over this period was also associated
      with depressive symptoms (odds ratio, 2.6; 95% CI, 1.0-6.7). These associations
      remained even after adjustment for initial depression score, as well as a range
      of potential confounding factors. CONCLUSIONS: Changes in estradiol and, to a
      lesser extent, in FSH levels are associated with an increased risk of depressive
      symptoms in postmenopausal women. These results further support a role for
      fluctuating rather than absolute hormone levels in depression in later life.

PMID- 19169166
TI  - Nonhormonal drug use and its relation to androgens in perimenopausal women: a
      population-based study of Swedish women. The Women's Health in the Lund Area
      Study.
AB  - OBJECTIVE: To outline the prevalence of nonhormonal drug use in middle-aged women
      and to assess plausible associations between serum androgen levels and variables
      associated to health such as drug use and planned visits to healthcare units.
      METHODS: This was a population-based study of women aged 50 to 59 years (n =
      6,893). Women were divided into three groups according to their menopause status:
      premenopausal (PM), postmenopausal without hormone therapy (PM0), and
      postmenopausal with hormone therapy (PMT). Data regarding current drug use and
      healthcare visits were collected from a questionnaire. RESULTS: The overall
      prevalence of nonhormonal drug use was 36.4% in all women. In the PM, PM0, and
      PMT groups, these percentages were 28.3%, 35.3%, and 39.3%, respectively, and the
      differences between them were statistically significant (P < 0.01). In all women,
      the most common medication used was for cardiovascular conditions (12.0%),
      followed by those for asthma (4.0%) and pain (3.7%). The number of drugs used by
      all women and women in the PM0 and the PMT groups were negatively associated with
      the serum levels of androstenedione (P < 0.05). In the postmenopausal groups, the
      number of visits to healthcare units was negatively associated to the levels of
      serum testosterone and androstenedione (P < 0.05). CONCLUSIONS: Hormone therapy
      in postmenopausal women seems to be associated with increased use of nonhormonal
      pharmacotherapy, rendering higher prevalence of such drugs in middle-aged women.
      Postmenopausal women with lower serum testosterone and a higher number of office
      visits used medications for cardiovascular problems and depression more than
      other medications. Whether this is an effect related to the hormone therapy
      itself or to experiencing more perimenopausal symptoms in this group of women is
      still unclear.

PMID- 19169167
TI  - Physical activity, menopause, and quality of life: the role of affect and self
      worth across time.
AB  - OBJECTIVE: Physical activity has been shown to enhance quality of life (QOL);
      however, few investigations of these effects exist in women undergoing the
      menopausal transition. The present study examined the long-term effects of
      physical activity on menopause-related QOL and tested the mediating effects of
      physical self-worth and positive affect in this relationship. METHODS: Middle
      aged women previously enrolled in a 4-month randomized controlled trial involving
      walking and yoga, and a control group completed a follow-up mail-in survey 2
      years after the end of the trial. The survey included a battery of psychological
      and physical activity measures, including measures of menopausal symptoms and
      menopause-related QOL. Longitudinal linear panel analysis was conducted within a
      covariance modeling framework to test whether physical self-worth and positive
      affect mediated the physical activity-QOL relationship over time. RESULTS: At the
      end of the trial, physical activity and menopausal symptoms were related to
      physical self-worth and positive affect, and in turn, greater levels of physical
      self-worth and positive affect were associated with higher levels of menopause
      related QOL. Analyses indicated that increases in physical activity and decreases
      in menopausal symptoms over the 2-year period were related to increases in
      physical self-worth (betas = 0.23 and -0.52, physical activity and menopausal
      symptoms, respectively) and, for symptoms, also to decreased positive affect
      (beta = -0.47), and both physical self-worth (beta = 0.34) and affect (beta =
      0.43) directly influenced enhancements in QOL (R = 0.775). CONCLUSIONS: The
      findings support the position that the effects of physical activity on QOL are
      mediated, in part, by intermediate psychological outcomes and that physical
      activity can have long-term benefits for women undergoing the menopausal
      transition.

PMID- 19169168
TI  - Effects of soy protein isolate on bone mineral density and physical performance
      indices in postmenopausal women--a 2-year randomized, double-blind, placebo
      controlled trial.
AB  - OBJECTIVE: Postmenopausal decreases in body composition, physical performance,
      and bone mass have been shown to be reversed by estrogen, but given the concerns
      regarding its use, women are looking for alternatives such as soy isoflavones.
      Most studies on the effects of soy on bone mineral density (BMD) in
      postmenopausal women have been short-term, that is, 3 to 6 months, and failed to
      provide conclusive evidence. There is no evidence of its effects on physical
      performance. The aim of the present study was to investigate the effects of soy
      plus isoflavones on BMD and physical performance in postmenopausal women.
      METHODS: This was a 2-year randomized controlled trial. A total of 203 healthy
      postmenopausal women were given either 25 g of soy protein without isoflavones,
      25 g of soy protein with 90 mg of isoflavones, or 25 g of milk protein (casein
      and whey) as a control agent for 24 months. Women were followed every 6 months
      with BMD and physical performance measurements for 2 years. Primary analysis was
      intent-to-treat analysis. Analysis of variance, chi and Fisher's exact tests, and
      analysis of covariance were used. RESULTS: There was a significant decrease in
      the BMD of the lumbar spine and femoral neck in those who completed the study in
      all groups. Soy isoflavones prevented major bone loss from baseline at the
      femoral trochanter with no between-group significance. Physical performance
      measurements decreased in all the groups. CONCLUSIONS: : Twenty-five grams of soy
      protein with 90 mg of isoflavones has no added benefit in preventing bone loss or
      improving physical performance.

PMID- 19169169
TI  - Yoga for menopausal symptoms: a systematic review.
AB  - OBJECTIVE: The aim of this study was to assess the effectiveness of yoga as a
      treatment option for menopausal symptoms. METHODS: We searched the literature
      using 14 databases from their inception to July 2008 and included all types of
      clinical studies regardless of their design. The methodological quality of all
      studies was assessed using a modified Jadad score. RESULTS: Seven studies met our
      inclusion criteria. Two randomized clinical trials compared the effects of yoga
      with those of walking or physical exercise. The meta-analysis of these data
      failed to show specific effects of yoga on menopausal complaints including
      psychological, somatic, and vasomotor symptoms. Two randomized clinical trials
      found no effects of yoga on total menopausal symptoms compared with wait-list
      control or no treatment. The remaining studies were either non-randomized (n = 1)
      or uncontrolled clinical trials (n = 3). They reported favorable effects of yoga
      on menopausal symptoms. These data collectively show that the results of rigorous
      studies of the effects of yoga for menopausal symptoms are unconvincing.
      CONCLUSION: The evidence is insufficient to suggest that yoga is an effective
      intervention for menopause. Further research is required to investigate whether
      there are specific benefits of yoga for treating menopausal symptoms.

PMID- 19169170
TI  - Additive effect of depressed mood and vasomotor symptoms on postmenopausal
      insomnia.
AB  - OBJECTIVE: The aim of this study was to investigate the role of vasomotor and
      mood symptoms on insomnia in postmenopausal women. METHODS: One hundred sixty
      three postmenopausal women, not receiving hormone therapy, attending a menopause
      clinic at the University of Athens, Greece, were included in this cross-sectional
      study. Climacteric symptoms were assessed by Greene's scale, whereas
      psychological morbidity was measured by Zung Self-Assessment Depression Scale,
      Symptom Checklist-90-R, and Athens Insomnia Scale. RESULTS: Vasomotor symptoms
      were significantly associated with insomnia (P = 0.001). When depressive
      symptomatology was added to the logistic regression analysis, the predictive
      ability of the model was significantly improved as defined by the increase in the
      log likelihood (P < 0.001) and the increase in the area under the receiver
      operating characteristic curve. CONCLUSIONS: Insomnia in postmenopausal women
      attending a menopause clinic is related both to the effects of vasomotor symptoms
      and depressive symptomatology. Mood symptoms seem to affect sleep independently
      of vasomotor symptoms, suggesting that depression should be carefully assessed
      and treated in postmenopausal women with insomnia.

PMID- 19169171
TI  - Amino acid malnutrition in patients with chronic pancreatitis and pancreatic
      carcinoma.
AB  - OBJECTIVES: Chronic pancreatitis (CP) and pancreatic cancer (CA) have been
      associated with intestinal malabsorption and inflammation. However, little is
      known about the changes in amino acid metabolism in such patients. METHODS: The
      circulating amino acid levels were determined in 12 patients with CP, 12 CA
      patients, and 12 controls. RESULTS: Total amino acid concentrations were 2850 +/-
      71 micromol/L in controls, 2640 +/- 96 micromol/L in CP patients, and 2210 +/-
      123 micromol/L in CA patients (P < 0.001). In CP patients, significant reductions
      in the concentrations of citrulline, gamma-aminobutyric acid, taurine, and
      aspartic acid were found (P < 0.05), whereas in CA patients, the levels of
      phosphoethanolamine, gamma-aminobutyric acid, aspartic acid, taurine, arginine,
      threonine, alanine, citrulline, and tryptophan were reduced. There was a
      significant inverse relationship between the total amino acid levels and the
      white blood cell counts (r = -0.44, P = 0.008). CONCLUSIONS: Both patients with
      CP and with CA exhibit alterations in amino acid levels. The mechanisms
      underlying these defects may involve intestinal malabsorption as well as systemic
      inflammation. Providing selective amino acid supplementation to such patients may
      minimize the excess morbidity and mortality associated with protein malnutrition.

PMID- 19169172
TI  - Correction of protein metabolic disorders by composite extract of Musa
      paradisiaca and Coccinia indica in streptozotocin-induced diabetic albino rat: an
      approach through the pancreas.
AB  - OBJECTIVE: The study focused on the ability of the extracts of Musa paradisiaca
      and Coccinia indica on protein metabolic disorders in streptozotocin (STZ)
      induced diabetes. METHODS: Wistar strain rats were divided into 6 groups as
      control, control + composite extract treated, STZ-induced diabetes, diabetic +
      composite extract treated, composite extract-pretreated diabetes, and composite
      extract-pretreated diabetes + composite extract treated. Protein metabolic status
      was assessed by serum levels of urea, uric acid, albumin, and creatinine along
      with urine urea and albumin levels. Diabetic therapeutic ability was assessed by
      blood glucose, glycated hemoglobin, and serum insulin levels. Histology of the
      pancreas, liver, and kidney was evaluated. RESULTS: Indices of protein metabolic
      disorders were deviated from control in STZ-induced diabetes, which were
      protected significantly after the treatment of composite extract of M.
      paradisiaca and C. indica. This protection was more prominent when the extract
      pretreated animals were subjected to diabetes induction by STZ. CONCLUSION: The
      composite extract has a protective therapeutic effect against diabetes through
      beta-cell regeneration capacity.

PMID- 19169173
TI  - Tracking intrahepatically transplanted islets labeled with Feridex
      polyethyleneimine complex using a clinical 3.0-T magnetic resonance imaging
      scanner.
AB  - OBJECTIVES: To evaluate the images acquired with a clinical 3.0-T magnetic
      resonance imaging machine as the quantification of transplanted and surviving
      islets in vivo. METHODS: Polyethyleneimine (PEI) was introduced to increase the
      labeling efficiency of Feridex, a dextran-coated superparamagnetic iron oxide.
      Allogeneic (Lewis-to-Wistar) and syngeneic (Wistar-to-Wistar) intraheptatic islet
      transplantations were performed to study the relationship among magnetic
      resonance imaging, metabolic monitoring, and pathological examination. RESULTS:
      After receiving Feridex-PEI-labeled islets, dark voids could be observed in the
      livers of both groups, accompanied with a significant decrease in liver/muscle
      intensity ratio from 1.25 +/- 0.03 to 1.09 +/- 0.05 (P < 0.01). One week after
      transplantation, islet grafts were rejected in the allogeneic group. Rapid
      disappearance of dark voids and a significant increase of liver/muscle ratio were
      observed. No islet grafts could be found in the paraffin sections of livers by
      that time. Meanwhile, in the syngeneic group, islet grafts survived indefinitely.
      Dark voids persisted and low liver/muscle ratios retained. The fact that the dark
      voids represented the labeled islets was confirmed by combined staining of
      insulin activity and Prussian blue. CONCLUSIONS: Either spot counting or signal
      intensity measurement provides a perfect quantification of transplanted and
      surviving islets in vivo. Feridex-PEI provides an effective and safe way to label
      islets.

PMID- 19169174
TI  - The prevalence of overweight and obesity in veterans with multiple sclerosis.
AB  - OBJECTIVES: To estimate the prevalence and factors associated with overweight and
      obesity in veterans with multiple sclerosis (MS) enrolled in the Veterans Health
      Administration (VA) and to compare the prevalence in this group with gender
      specific published rates for the general population of veterans receiving
      outpatient care at VA medical facilities. DESIGN: Cross-sectional cohort study
      linking electronic medical record information to mailed survey from 1999 to 2004.
      A total of 4703 veterans with MS enrolled in VA who returned questionnaires as
      part of two cross-sectional studies. Main outcome measures included body mass
      index, demographic information, Veteran RAND 36-item Health Survey, frequency of
      physical exercise, and other health conditions. RESULTS: Overall, 28% of female
      and 42.8% of male veterans with MS were overweight. Another 25% of women and
      21.2% of male veterans met the criteria for obesity. Compared with a historical
      cohort of veterans enrolled in the VA, veterans with MS had a slightly higher
      adjusted prevalence of overweight than did veterans in general (42.3% vs. 39.6%,
      respectively) but a lower adjusted prevalence of obesity (20.1% vs. 33.1%). In
      adjusted logistic regression, age, smoking, and lower levels of pain were
      associated with a lower likelihood of overweight or obesity. Being male, married,
      employed and having arthritis and diabetes were associated with a greater
      likelihood of overweight or obesity. CONCLUSIONS: Overweight and obesity are a
      problem for more than 60% of veterans with MS in the VA. Screening for overweight
      and obesity should be done routinely. Interventions to prevent and manage
      excessive weight in individuals with MS should be developed and evaluated.

PMID- 19169175
TI  - Disparities in postacute stroke rehabilitation disposition to acute inpatient
      rehabilitation vs. home: findings from the North Carolina Hospital Discharge
      Database.
AB  - OBJECTIVE: We evaluated the factors associated with discharge disposition to
      either inpatient rehabilitation or home after acute stroke hospitalization.
      DESIGN: We analyzed data from three concurrent years of State Hospital Discharge
      Data (years 2002-2004) of patients admitted with a primary International
      Classification of Diseases-9 code diagnosis of 430-434.9 and 436 (n = 7810).
      Logistic regression models tested whether discharge to inpatient rehabilitation
      vs. home was associated with socio-demographic factors. We controlled for
      covariates, including medical factors, such as number of intensive care unit
      days, Charlson Comorbidity Index, therapy charges, and available resources in
      their county. RESULTS: We found that older age, a greater number of intensive
      care unit days, higher total therapy charges, and lower poverty in their county
      of residence were associated with discharge to acute inpatient rehabilitation.
      Factors associated with discharge to home included younger age, fewer intensive
      care unit days, lower therapy charges, and higher poverty in their county of
      residence. CONCLUSIONS: Enabling factors, such as county poverty status and
      exposure to therapy may be important factors related to postacute stroke
      disposition.

PMID- 19169176
TI  - Low-back pain in transfemoral amputees: is there a correlation with static or
      dynamic leg-length discrepancy?
AB  - OBJECTIVE: Low-back pain (LBP) is an important cause of secondary disability in
      transfemoral amputees (TFA). The correction of leg-length discrepancy (LLD) is a
      common clinical approach to the treatment of LBP in this population. The aim of
      our study is to assess the relationship of static and dynamic LLD and LBP in a
      sample TFA population. DESIGN: Nine TFA with LBP and eight TFA without LBP were
      studied. Static leg length was measured with subjects standing in a self-selected
      comfortable position. Dynamic leg length was measured during the single-limb
      support and double-limb support phases of the gait cycle. RESULTS: There were no
      statistically significant differences between the pain and no pain groups in
      terms of static LLD (P = 1.0; 95% confidence interval, -6.8 to 6.6 mm); dynamic
      LLD during single-limb support (P = 0.3; 95% confidence interval, -27.3 to 7.3
      mm); dynamic LLD during double-limb support with either the prosthetic limb
      leading (P = 0.3; 95% confidence interval, -4.0 to 12.2 mm) or the intact foot
      leading (P = 0.8, 95% confidence interval, -6.4 to 7.8 mm). CONCLUSIONS: This
      study calls into question whether LLD plays a significant role in persistence of
      LBP in TFA. Further study of the effects of LLD and its possible relationship to
      causation of LBP in amputees is needed.

PMID- 19169177
TI  - Transitory myocardial ischemia in patients with vascular lower limb amputation:
      relationship with long-term atherothrombotic events.
AB  - OBJECTIVE: To evaluate the prevalence of asymptomatic transitory myocardial
      ischemia during scintigraphy among amputees of vascular etiology as well as to
      ascertain correlation with atherothrombotic events during long-term follow-up.
      DESIGN: A cohort, mean follow-up of 2.1 yrs study was performed in an outpatient
      rehabilitation clinic with 58 lower limb vascular amputees who were referred for
      rehabilitation, asymptomatic for coronary heart disease. Patients were evaluated
      for myocardial ischemia by dipyridamole scintigraphy, and occurrence of severe
      cardiovascular events (death, acute myocardial infarction, stroke, and peripheral
      ischemia with hospitalization) was assessed. RESULTS: Of the 58 patients, 26
      (44.8%) had positive dipyridamole myocardial scintigraphy for transitory
      myocardial ischemia. During follow-up, 12 subjects (20.7%), mainly diabetic
      patients (83%), registered a serious cardiovascular event, with 9 of 12 events
      having occurred in those who had tested positive for transitory ischemia on
      scintigraphy (P < 0.025). There were five deaths (19.2%) in those with a positive
      scintigraphy and a single death (3.1%) in those with a negative dipyridamole
      test, although the Kaplan-Meier survival curve and Cox regression were not
      significant (P = 0.09 and 0.1, respectively). CONCLUSIONS: We found that 44.8% of
      patients with vascular lower limb amputation, asymptomatic for coronary disease,
      tested positive on myocardial scintigraphy for transitory myocardial ischemia. In
      a mean follow-up of 2.1 yrs, there was 10.3% of atherothrombotic events/year,
      with a higher death toll in those patients with positive scintigraphy.

PMID- 19169179
TI  - Elite male adolescent gymnast who achieved union of a persistent bilateral pars
      defect.
AB  - An adolescent 15-yr-old male competitive gymnast presented to a university-based
      multidisciplinary spine institute with a persistent low-back pain for 18 mos.
      Although the results of x-rays were negative, his pain rendered him unable to
      compete in his sport any longer. A computed tomography scan was performed, which
      showed a bilateral pars fracture at L5, without spondylolisthesis. A nuclear
      medicine bone scan revealed negative findings, confirming chronic nonunion. The
      patient completed a 4-wk course of physical therapy 6 mos before our
      intervention, without any relief of pain or radiologic evidence of healing. The
      patient was treated with a bone stimulator for 4 hrs/day and was recommended to
      wear a warm-and-form-type brace. Isometric core trunk exercises were also
      initiated. Only after 6 wks of treatment, the subject showed clinical improvement
      at the follow-up visit. Computed tomography scan performed 12 wks after the
      initial scan showed complete union of the fracture correlating with clinical
      improvement. Two years later, the athlete remains completely pain-free, is
      training regularly, and is able to compete on a national and, possibly,
      international level.

PMID- 19169180
TI  - The dream of a medical specialty named physical and rehabilitation medicine: a
      commentary on the European White Book of Physical and Rehabilitation Medicine.

PMID- 19169178
TI  - The effect of muscle loading on skeletal muscle regenerative potential: an update
      of current research findings relating to aging and neuromuscular pathology.
AB  - Skeletal muscle is a dynamic tissue with a remarkable ability to continuously
      respond to environmental stimuli. Among its adaptive responses is the widely
      investigated ability of skeletal muscle to regenerate after loading or injury or
      both. Although significant basic science efforts have been dedicated to better
      understand the underlying mechanism controlling skeletal muscle regeneration,
      there has been relatively little impact in the clinical approaches used to treat
      skeletal muscle injuries and wasting. The purpose of this review article is to
      provide an overview of the basic biology of satellite cell function in response
      to muscle loading and to relate these findings in the context of aging and
      neuromuscular pathology for the rehabilitation medicine specialist.

PMID- 19169181
TI  - Dextrocardia associated with left-sided Poland syndrome.

PMID- 19169182
TI  - New technologies: the good, the bad, and the ugly.

PMID- 19169183
TI  - How we see others: the psychobiology of schemas and transference.
AB  - Social cognition involves automatic and stimulus-driven processes; these may be
      important in mediating stereotypes in the community and schemas and transference
      in the clinic setting. Significant differences in self-related processing and
      other-related processing may also lead to important biases in our view of the
      other. The psychobiology of social cognition is gradually being delineated, and
      may be useful in understanding these phenomena, and in responding appropriately.
      In the clinic, schemas can be rigorously assessed, and schema-focused
      psychotherapy may be useful in a number of indications.

PMID- 19169184
TI  - An atypical presentation of anton syndrome in a patient with preserved cognition
      despite multiple cerebral infarcts: a case report.

PMID- 19169185
TI  - DNA microarray technology in the clinical environment: the AmpliChip CYP450 test
      for CYP2D6 and CYP2C19 genotyping.
AB  - INTRODUCTION: An important technological advance in genetic testing is the DNA
      microarray, which allows for the simultaneous testing of thousands of DNA
      sequences. The AmpliChip CYP450 Test employs this microarray technology for
      cytochrome P450 (CYP) 2D6 and CYP2C19 genotyping. Isoenzymes encoded by these
      genes are responsible for the metabolism of many widely prescribed drugs. The
      objectives of this study were to identify CYP2D6 and CYP2C19 alleles and
      phenotypes in a psychiatric patient population in Kentucky, and to describe
      practical issues associated with DNA microarray technology. METHODS: A total of
      4,532 psychiatric patients were recruited from three state hospitals in Kentucky.
      Whole blood, buccal swabs, or saliva samples were genotyped with the AmpliChip
      CYP450 Test to derive a predicted phenotype. RESULTS: In this cohort, the overall
      prevalence of CYP2D6 poor metabolizers was 7.6% (95% CI 7%, 8.3%), 8.2% in the
      Caucasians (95% CI 7.4%, 9.%) and 1.8% in the African Americans (95% CI 0.9%,
      3.5%). The overall prevalence of CYP2D6 ultrarapid metabolizers was 1.5% (95% CI
      1.2%, 1.9%), 1.5% in the Caucasians (95% CI 1.1%, 1.9%) and 2.0% in the African
      Americans (95% CI 1.1%, 3.7%). The overall prevalence of CYP2C19 poor
      metabolizers was 2.0% (95% CI 1.8%, 2.7%), 2.2% in Caucasians (95% CI 1.6%, 2.5%)
      and 4.0% in African Americans (95% CI 2.6%, 6.1%). CONCLUSION: We also propose a
      numeric system for expression of CYP2D6 and CYP2C19 enzyme activity to aid
      clinicians in determining treatment strategy for patients receiving therapeutics
      that are metabolized by the CYP2D6 or CYP2C19 gene products.

PMID- 19169186
TI  - Treatment-refractory schizoaffective disorder in a patient with dyke-davidoff
      masson syndrome.
AB  - Dyke-Davidoff-Masson syndrome, or cerebral hemiatrophy, is a pre- or perinatally
      acquired entity characterized by predominantly neurologic symptoms, such as
      seizures, facial asymmetry, contralateral hemiplegia, and mental retardation.
      Psychiatric symptoms are rarely reported. We report the first case of left
      cerebral hemiatrophy and a late onset of treatment-resistant schizoaffective
      disorder after a stressful life event. The patient finally responded well to
      clozapine. The clinical history and results from structural neuroimaging are
      highlighted to discuss the possible developmental bias for psychotic disorders.

PMID- 19169187
TI  - A placebo-controlled study evaluating the efficacy and safety of flexible-dose
      desvenlafaxine treatment in outpatients with major depressive disorder.
AB  - INTRODUCTION: This research compares the efficacy and safety of desvenlafaxine
      (administered as desvenlafaxine succinate) versus placebo in treating major
      depressive disorder. METHODS: In this randomized, double-blind study, outpatients
      with major depressive disorder > or =18 years of age received desvenlafaxine 200
      400 mg/day or placebo for 8 weeks. Efficacy endpoints included (primary) change
      in 17-item Hamilton Rating Scale for Depression score at the final evaluation
      (last observation carried forward, analysis of covariance) and (secondary)
      Clinical Global Impressions-Improvement and -Severity of Illness scales. RESULTS:
      The difference between desvenlafaxine (n==) and placebo (n==) on the primary
      endpoint was not significant (-9.1 vs -7.5, P=.078). Week 8 observed cases
      (desvenlafaxine, n=80; placebo, n=94) results were significant (-10.7 vs -7.9,
      P=.008). Differences at the final evaluation (last observation carried forward)
      were significant for Clinical Global Impressions-Improvement (2.9 vs 2.5, P=.037)
      and Clinical Global Impressions-Severity of Illness (-1.9 vs -1.2, P=.041).
      Discontinuation rates due to adverse events (AEs) were 12% and 3% for
      desvenlafaxine and placebo, respectively (P=.008). The most frequently reported
      AE associated with desvenlafaxine was nausea (36% vs 9% [placebo]). CONCLUSION:
      In this study, the primary analysis did not show significant differences between
      desvenlafaxine and placebo; discontinuations due to AEs associated with the
      desvenlafaxine dose range may have contributed to the lack of statistical
      separation.

PMID- 19169188
TI  - The Cape Town consensus on posttraumatic stress disorder: introduction.

PMID- 19169189
TI  - Posttraumatic stress disorder: diagnostic and epidemiological perspectives.
AB  - We reviewed epidemiological findings for the diagnosis of posttraumatic stress
      disorder (PTSD) and its core diagnostic features, focusing on whether
      epidemiology has been helpful in clarifying some of the critical diagnostic
      issues relevant to the revision of the Diagnostic and Statistical Manual of
      Mental Disorders and the International Statistical Classification of Diseases.
      Though epidemiology has provided increasingly rich data and knowledge regarding
      prevalence and incidence, patterns of onset and course, comorbidity, and risk
      factors for traumatic experiences and posttraumatic stress, little systematic
      research has been performed specifically addressing such critical diagnostic
      issues. Particularly, unresolved concerns remain regarding the definition of
      trauma, duration and impairment/distress criteria, the distinctiveness of the
      PTSD-syndrome, and even the position of PTSD in the classification system of
      mental disorders. A further exploitation of the existing data, and an improvement
      of existing epidemiological methods, strategies, and assessments are likely to
      substantially contribute to the clarification of unresolved diagnostic issues.

PMID- 19169190
TI  - Neurobiology of posttraumatic stress disorder.
AB  - Exposure to a traumatic event is required for the diagnosis of posttraumatic
      stress disorder (PTSD). The symptoms of PTSD are believed to reflect stress
      induced changes in neurobiological systems and/or an inadequate adaptation of
      neurobiological systems to exposure to severe stressors. More recently, there
      have been attempts to link the identified neurobiological changes to the specific
      features that constitute PTSD, such as altered mechanisms of learning and
      extinction, sensitization to stress, and arousal. Furthermore, there have been
      efforts to understand whether certain neurobiological changes in PTSD reflect
      preexisting vulnerability factors rather than consequences of trauma exposure or
      correlates of PTSD. Genetic variability, sex differences, and developmental
      exposures to stress influence neurobiological systems and moderate PTSD risk. On
      the basis of these findings, important hypotheses for developing novel strategies
      to identify subjects at risk, promote resilience, and devise targets for the
      prevention or treatment of PTSD can be derived.

PMID- 19169191
TI  - Pharmacotherapy of posttraumatic stress disorder: a review of meta-analyses and
      treatment guidelines.
AB  - BACKGROUND: A number of randomized controlled trials of the pharmacotherapy of
      posttraumatic stress disorder (PTSD) are now available. Several meta-analyses of
      these trials, and a number of consensus guidelines on the treatment of PTSD, have
      been published. Assessment of these meta-analyses and guidelines provides an
      opportunity to review the strengths and weaknesses of the evidence-base. METHODS:
      Meta-analyses of PTSD trials were assessed with the quality of reporting of meta
      analyses (QUOROM) statement and the Oxman and Guyatt rating scale, and consensus
      statements on the treatment of PTSD were assessed with the Appraisal of
      Guidelines Research and Evaluation instrument. Summary statistics of meta
      analyses and conclusions of guidelines were tabulated. RESULTS: The quality of
      PTSD meta-analyses and guidelines is generally acceptable. Many consensus
      guidelines have emphasized the value of pharmacotherapy for PTSD. Consensus
      statements have, however, used different approaches, and their conclusions have
      differed. Many important questions for the field have not yet been adequately
      researched. CONCLUSIONS: There have been significant advances in the
      pharmacotherapy of PTSD, and certain medications (eg, selective serotonin
      reuptake inhibitors) are appropriately viewed as a first-line treatment for adult
      PTSD. Nevertheless, as is the case in other anxiety disorders, there is a paucity
      of longer-term trials, data on treatment effectiveness in wider clinical
      practice, and data on treatment-resistant patients.

PMID- 19169192
TI  - Effective psychotherapies for posttraumatic stress disorder: a review and
      critique.
AB  - This report reviews and critiques the psychotherapy literature for the treatment
      of posttraumatic stress disorder (PTSD) and systematically presents data on
      sample size, rates of completion and effect sizes. Substantial progress has been
      made in the use of cognitive behavioral therapies and eye movement
      desensitization and reprocessing for the resolution of PTSD. Innovations in PTSD
      treatments are identified. Further advances are needed in the treatment of
      populations with complex and chronic forms of PTSD such as those found in
      childhood abuse populations, refugee populations, and those experiencing chronic
      mental illness. The need to address comorbid emotional, social, and physical
      health consequences of trauma, to implement treatments in community-based
      settings, and to incorporate larger systems of care into study designs is noted.

PMID- 19169193
TI  - Can posttraumatic stress disorder be prevented?
AB  - After trauma, it is often possible to prevent, or at least reduce the effect of,
      certain medical sequelae if intervention occurs within a particular time period:
      "the golden hour(s)". The possibility of a similar window of opportunity in
      posttraumatic stress disorder (PTSD) is discussed here. The essence of acute
      distress management should be to help contain and attenuate emotional reaction,
      and to encourage a return to full function and activity. Early intervention at
      this point could prevent the subsequent development of PTSD. Preclinical and
      clinical data suggest that amnesia of the traumatic event is associated with a
      decreased prevalence of PTSD, and that debriefing is not necessarily beneficial.
      Randomized, placebo-controlled studies are needed in order to examine what
      psychological and/or pharmacological interventions should or should not be made
      during the "golden hours" following trauma.

PMID- 19169194
TI  - Cape Town consensus on posttraumatic stress disorder.
AB  - The association between traumatic events and psychopathology has long been
      recognized, and the literature on posttraumatic stress disorder (PTSD) has
      burgeoned since this entity was introduced into the diagnostic nomenclature. This
      literature has been characterized by a range of clinical controversies about the
      optimal diagnosis and treatment of PTSD. In response, several systematic reviews
      of treatment, clinical guidelines, and consensus statements about PTSD have been
      generated, but their conclusions are not always consistent. Our aim here is to
      provide a concise overview of the literature on PTSD, focusing in particular on
      recent investigations and publications, with the objective of summarizing
      practical clinical implications and suggesting future research opportunities. We
      consider, in turn, the diagnosis and evaluation, psychobiology, pharmacotherapy,
      psychotherapy, and prevention of PTSD.

PMID- 19169195
TI  - The role of L-methylfolate in depressive disorders.
AB  - Major depressive disorder (MDD) is a debilitating and often recurrent illness. An
      initial antidepressant trial is effective at achieving remission for
      approximately 30% of patients when prescribed as monotherapy, with the majority
      of patients returning as partial or non-responders. Switching antidepressants or
      adding augmentation agents are standard therapeutic options used to achieve and
      maintain remission. Suboptimal serum and red blood cell folate levels have been
      associated with a poorer response to antidepressant therapy, a greater severity
      of symptoms, later onset of clinical improvement, and overall treatment
      resistance. This Expert Review Supplement reviews the evidence for L-methylfolate
      as an augmentation agent in depression and discusses its clinical use elaborated
      by three clinical presentations.

PMID- 19169196
TI  - The role of L-methylfolate in depressive disorders: commentary.

PMID- 19169198
TI  - Antimutagenic activity and radical scavenging activity of water infusions and
      phenolics from ligustrum plants leaves.
AB  - Water infusions of Ligustrum delavayanum and Ligustrum vulgare leaves and eight
      phenolics isolated therefrom have been assayed in vitro on ofloxacin-induced
      genotoxicity in the unicellular flagellate Euglena gracilis. The tested compounds
      luteolin, quercetin, luteolin-7-glucoside, luteolin-7-rutinoside, quercetin-3
      rutinoside, apigenin-7-rutinoside, tyrosol and esculetin inhibited the mutagenic
      activity of ofloxacin (43 microM) in E. gracilis. Water infusions from leaves of
      L. delavayanum and L. vulgare showed higher antimutagenic effect (p(t) < 0.001).
      The activity of these samples against ofloxacin (86 microM)-induced genotoxicity
      was lower, but statistically significant (p(t) < 0.05), excluding the water
      infusion of L. delavayanum leaves (p(t) < 0.01). Efficacy of quercetin, luteolin
      7-rutinoside, apigenin-7-rutinoside was insignificant. The antimutagenic effect
      of most phenolics we studied could be clearly ascribed to their DPPH scavenging
      activity, substitution patterns and lipophilicity.

PMID- 19169199
TI  - Antimicrobial activity of some thiourea derivatives and their nickel and copper
      complexes.
AB  - Five thiourea derivative ligands and their Ni(2+) and Cu(2+) complexes have been
      synthesized. The compounds were screened for their in vitro anti-bacterial
      activity using Gram-positive bacteria (two different standard strains of
      Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis,
      Streptococcus pyogenes, Bacillus cereus) and Gram-negative bacteria (Esherichia
      coli, Pseudomonas aeruginosa, Enterobacter cloacae, Proteus vulgaris,
      Enterobacter aerogenes) and in vitro anti-yeast activity (Candida albicans,
      Candida krusei, Candida glabrata, Candida tropicalis, Candida parapsilosis). The
      minimum inhibitory concentration was determined for all ligands and their
      complexes. In vitro anti-yeast activity of both ligands and their metal complexes
      is greater than their in vitro anti-bacterial activity. The effect of the
      structure of the investigated compounds on the antimicrobial activity is
      discussed.

PMID- 19169200
TI  - "Flash" solvent-free synthesis of triazoles using a supported catalyst.
AB  - A solvent-free synthesis of 1,4-disubstituted-1,2,3-triazoles using neat azides
      and alkynes and a copper(I) polymer supported catalyst (Amberlyst) A21*CuI) is
      presented herein. As it provides the products in high yields and purities within
      minutes, this method thus being characterized as a "flash" synthesis, and was
      exemplified through the synthesis of a 24-compound library on a small scale.

PMID- 19169202
TI  - Optimization and comparison of five methods for extraction of coniferyl ferulate
      from Angelica sinensis.
AB  - Coniferyl ferulate, which is noted for its multiple pharmacological activities
      and chemical instability, is abundant in Angelica sinensis. In this paper, five
      methods, namely sonication extraction (SE), pressurized liquid extraction (PLE),
      supercritical fluid extraction (SFE), hydrodistillation (HD) and decoction (DC)
      for extraction of coniferyl ferulate, as well as ferulic acid, Z/E-ligustilide
      and Z/E-butylidenephthalide, from A. sinensis were optimized and compared. The
      results showed that the order of extraction efficiency was: PLE>>SE>SFE>>HD, DC.
      The compositions of the SE, PLE and SFE extracts, which had a high ratio of
      coniferyl ferulate, were very similar, while no coniferyl ferulate was obtained
      by HD and DC, though they had high selectivity for the extraction of ligustilide
      and ferulic acid, respectively. It was noteworthy that the content of ligustilide
      and coniferyl ferulate was not detectable in the decoction, the commonly used
      oral administration form of Traditional Chinese Medicines in clinical practice.

PMID- 19169201
TI  - Biological and pharmacological activities of squalene and related compounds:
      potential uses in cosmetic dermatology.
AB  - Squalene is a triterpene that is an intermediate in the cholesterol biosynthesis
      pathway. It was so named because of its occurrence in shark liver oil, which
      contains large quantities and is considered its richest source. However, it is
      widely distributed in nature, with reasonable amounts found in olive oil, palm
      oil, wheat-germ oil, amaranth oil, and rice bran oil. Squalene, the main
      component of skin surface polyunsaturated lipids, shows some advantages for the
      skin as an emollient and antioxidant, and for hydration and its antitumor
      activities. It is also used as a material in topically applied vehicles such as
      lipid emulsions and nanostructured lipid carriers (NLCs). Substances related to
      squalene, including beta-carotene, coenzyme Q10 (ubiquinone) and vitamins A, E,
      and K, are also included in this review article to introduce their benefits to
      skin physiology. We summarize investigations performed in previous reports from
      both in vitro and in vivo models.

PMID- 19169203
TI  - Rubiacordone A: a new anthraquinone glycoside from the roots of Rubia cordifolia.
AB  - A new anthraquinone, Rubiacordone A (1) (6-acetoxy-1-hydroxy-2
      methylanthraquinone-3-O-alpha-L-rhamnopyranoside), was isolated together with the
      known anthraquinone, 1-acetoxy-6-hydroxy-2-methylanthraquinone-3-O-[alpha-L
      rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside] (2), from the dried roots of
      Rubia cordifolia. Their structures were elucidated on the basis of extensive 1D
      and 2D-NMR, as well as HRESI-MS spectroscopic analysis. Metabolites 1 and 2
      showed considerable antimicrobial activity against Gram-positive bacteria.

PMID- 19169204
TI  - Antiosteoporotic activity of anthraquinones from Morinda officinalis on
      osteoblasts and osteoclasts.
AB  - Bioactivity-guided fractionation led to the successful isolation of
      antiosteoporotic components, i.e. physicion (1), rubiadin-1-methyl ether (2), 2
      hydroxy-1-methoxy- anthraquinone (3), 1,2-dihydroxy-3-methylanthraquinone (4),
      1,3,8-trihydroxy-2-methoxy- anthraquinone (5), 2-hydroxymethyl-3
      hydroxyanthraquinone (6), 2-methoxyanthraquinone (7) and scopoletin (8) from an
      ethanolic extract of the roots of Morinda officinalis. Compounds 4-8 are isolated
      for the first time from M. officinalis. Among them, compounds 2 and 3 promoted
      osteoblast proliferation, while compounds 4, 5 increased osteoblast ALP activity.
      All of the isolated compounds inhibited osteoclast TRAP activity and bone
      resorption, and the inhibitory effects on osteoclastic bone resorption of
      compounds 1 and 5 were stronger than that of other compounds. Taken together,
      antiosteoporotic activity of M. officinalis and its anthraquinones suggest
      therapeutic potential against osteoporosis.

PMID- 19169205
TI  - Results from the monitoring use programme for endovascular repair of abdominal
      aortic aneurysms in Spain.
AB  - AIM: The aim of this study was to present the results from the Monitoring Use
      Programme (MUP) for endovascular repair (ER) of abdominal aortic aneurysms (AAA)
      using stent grafts in Spain, carried out to determine the procedure's
      effectiveness and safety. METHODS: This was a follow-up study carried out through
      a multicentric-case registry between 2001-2003. Variables were grouped into: 1)
      general information, 2) postoperative period and 3) follow-up period. RESULTS:
      The study enrolled 740 cases (97% males), from 32 hospitals. Mean age of patients
      was 72.7+/-7.3 years. Mean AAA diameter was 59.5+/-13.7 mm. Forty-seven percent
      of patients required additional intervention procedures; 19% patients presented
      intervention complications (53% were endoleaks). The endovascular intervention
      could not be completed in 6 patients, and in 2 patients the operation was changed
      to conventional surgery; 24% patients suffered, mostly minor, postoperative
      complications. Between 4-24 months, follow-up was normal in 81-85% cases with the
      most common complication being endoleaks (7%). After 24 months, and especially
      after 37, reinterventions and complications, in particular angulation and stent
      migration, increased, mainly associated to the Vanguard device. After 37 months,
      an increase in AAA size was observed. Among patients with preoperative AAA<50 mm,
      there was a greater proportion of individuals requiring additional procedures
      (60% vs 41%, P<0.01), suffering postoperative complications (26% vs 24%), and
      presenting more leaks (71% vs 52%), than among patients with AAA >or= 50 mm.
      CONCLUSIONS: ER of AAA shows favourable results in the short/medium term with
      regards to procedure safety and effectiveness. The appearance of some
      complications and increase in AAA size 2-3 years after ER raises the need for
      caution. Care should be taken when considering ER of small AAA.

PMID- 19169206
TI  - Transcarotideal access for endovascular repair of descending thoracic aortic
      aneurysm with intentional coverage of celiac artery.
AB  - Endovascular treatment of thoracic and thoraco-abdominal aortic aneurysm with
      celiac artery ostium coverage, seems to be safe according to the literature. We
      present a case in which the endograft deployement was achieved through a right
      common carotid artery access because four years before the patient was submitted
      to an axillo-bifemoral bypass with aortic graft removal and aortic stump ligature
      for infection. After endovascular repair the patient suffered from spinal cord
      ischemia, acute pancreatitis and spleen infarction. Probably, the new pancreatic
      event has been triggered by temporary visceral ischemia, acting on a pancreas
      damaged by a previous acute hemorrhagic pancreatitis.

PMID- 19169207
TI  - A telephone survey on the reasons for non-attendance in a dermatological clinic.
AB  - AIM: Long waiting time before obtain medical attention is a significant problem
      that affects all specialties and especially dermatology, where a quick
      observation is required because of the rapid mutation of skin lesions pattern.
      Non-attendance (NA) is one of the aspects that is most involved in the length of
      waiting lists. The aim of this study was to investigate the different reasons for
      NA in the dermatological clinic as to improve the booking system and allow
      patients to be visited in a shorter time. METHODS: All the patients who failed to
      attend a visit, booked in the dermatological service during a two months period,
      were contacted by telephone to determine the reasons for having missed the
      appointment. For each patient details as age, sex, kind of visit (initial visit,
      follow-up visit or visit with priority level) and type of clinic (general
      dermatology, second level dermatology or paediatric dermatology) were collected
      and analyzed. RESULTS: The overall NA rate was 11.19% and different reasons for
      NA were found, namely forgetfulness of the appointment, work-related problems and
      concomitant illness. CONCLUSION: The most frequent reason for NA is forgetfulness
      of the appointment and it could be explained by the long time elapsing between
      booking and visit. Different techniques to reduce forgetfulness have been
      suggested; in our case the use of a unique call centre that coordinates booking
      for all the health structures in Milan and the sending of a reminder mobile
      message have led to good results with a NA rate lower than in other studies.

PMID- 19169208
TI  - Granuloma annulare.
AB  - AIM: Granuloma annulare (GA) is a palisading granulomatous skin disease. It is a
      relatively common dermatosis typically characterized by an annular arrangement of
      erythematous or flesh-coloured papules. The aim of this study was to assess the
      epidemiological and clinical pattern of GA and its management. METHODS: A
      retrospective study dealing with 35 cases of GA collected during an 11-year
      period from 1995 to 2005 was carried out at the Dermatology Department of Charles
      Nicolle's Hospital of Tunis. RESULTS: There were 24 females and 11 males
      including 13 children. Four clinical patterns were observed: localized GA with
      annular shaped lesions in 22 cases (62.8%), subcutaneous GA in 9 cases (25.7%)
      with 4 children, combination of localized and subcutaneous patterns in one child
      (2.8%), generalized GA in one adult-patient (2.8%) and combination of generalized
      and subcutaneous patterns in 2 cases (5.7%). Associated diabetes mellitus was
      seen in 9 adults (25%) and thyroid diseases in 2 other adults (5.7%). Topical
      steroids were proposed in 9 cases with partial resolution in 6 of them. Four
      patients were treated by hydroxychloroquine with an improvement in 3 of them. Two
      patients (generalized GA with subcutaneous form and subcutaneous GA) were treated
      by dapsone with partial clearing. CONCLUSION: In these series, GA has the same
      epidemiological and clinical pattern as other series of the literature.
      Subcutaneous form had a pseudo-rheumatoid presentation in adults and an exclusive
      involvement of children when it is localized on the scalp. Associated systemic
      diseases, especially diabetes mellitus, are frequent in the series here observed.

PMID- 19169209
TI  - Molecular biology and targeted therapy of cutaneous T-cell lymphomas.
AB  - Cutaneous T-cell lymphoma (CTCL) is an extra-nodal non-Hodgkin lymphoma of mature
      T cells. These tumor cells home to and persist in the skin, producing a broad
      spectrum of clinical entities. Recent results of basic research on tumor biology
      and tumor immunology as well as molecular genetics of cutaneous T-cell lymphoma
      have fostered the development of new therapeutic approaches. Several clinical
      trials testing these targeted therapies have shown encouraging results. This
      article provides an overview of recent research developments and therapeutic
      strategies for cutaneous T-cell lymphoma.

PMID- 19169210
TI  - Immunopathogenesis of mycosis fungoides/Sezary syndrome (cutaneous T-cell
      lymphoma).
AB  - T cells are critical effectors of the adaptive immune response and play an
      important role in cutaneous immunity. In the skin, various cell types cooperate
      together, from components of both the innate immunity and adaptive immunity,
      provide sentinel function to mediate the immune response. However, when T cell
      function becomes abnormal, there is a loss of normal effector immune function,
      and the abnormal T cells become a cause of disease as well. Mycosis fungoides
      (MF) is a cutaneous T cell lymphoma (CTCL) that preferentially travels to the
      epidermis. When skin homing T cells become malignant, the clinical consequences
      reflect not only the presence of the malignant cells, but likely from a complex
      reaction of the immune response to the malignant cell. The clinical presentation
      is the evolving manifestation of the steps in cancer immunosurveillance. Analysis
      of gene expression in MF/CTCL patients has provided support for the role of the
      immune response in the early phase of the disease and a loss of immune response
      in advance stages of MF/CTCL. This review will focus on cytokine gene expression
      abnormalities in the clinical stages of the disease and discuss the relationship
      between the clinical and immunologic abnormalities to gain a better understanding
      of mechanisms important in the evolution of this disease. A better understanding
      of the immunopathogenesis of MF/CTCL would support innovative strategies for the
      development of novel therapies to treat this T cell malignancy.

PMID- 19169211
TI  - The molecular pathogenesis of mycosis fungoides and Sezary syndrome.
AB  - Mycosis fungoides (MF) and the Sezary syndrome (Sz) are the two most frequent
      forms of cutaneous T cell lymphomas (CTCL). Generally the Sz is regarded as a
      leukemic variant of MF. They are caused by malignant CD4+ T cells, which
      infiltrate the skin and both diseases proceed in different stages. It has been
      found in colon carcinoma that cancerogenesis is a sequence of activation of
      different oncogenes and inactivation of tumor suppressor genes. This finding has
      initiated efforts to identify the genes that are responsible for the progression
      of MF and Sz. The development of new screening methods has strongly accelerated
      this search and many oncogenes and tumor suppressor genes have been identified
      that may play a role in the progression of both diseases. Changes in the
      expression of some of these genes are already found at early stages, whereas
      others become active or inactivated only in later stages. These results will help
      to search for more specific drugs and lead to a more exact staging that will help
      to develop effective and personalized treatments of these diseases.

PMID- 19169212
TI  - The treatment of mycosis fungoides.
AB  - Primary cutaneous T-cell lymphomas (PCLs) mycosis fungoides (MF) and Sezary
      syndrome (Ss) belong to the group of non-Hodgkin lymphomas (NHL), which are
      characterized by clonally proliferating CD4+ cells localized in the skin.
      Although there already exist many conventional skin-directed and systemic
      cytotoxic treatment options, in long-term only a transient remission without
      curative results will be reached in most cases. The aim of this article was to
      present actual assumed treatment modalities, as well as new therapeutic
      strategies which passed already through clinical trials showing promising results
      in the treatment of PCLs.

PMID- 19169213
TI  - Follicular mycosis fungoides: a histopathologic, immunohistochemical, and
      genotypic review.
AB  - Follicular mycosis fungoides (FMF) is a recognized variant of mycosis fungoides.
      In this review, the authors characterize the distinct histopathological and
      immunohistochemical patterns of FMF that have been reported in the literature.
      This article is an extensive review of the literature cited in Medline and own
      data of the authors. The major patterns of FMF histopathology,
      immunohistochemistry, and molecular genetics are summarized in this review.
      Histologically, the quintessential finding in FMF is small to medium atypical
      CD3+ CD4+ CD8- T lymphocytes around and within the epithelium of the hair
      follicles. This finding is requisite to the diagnosis. However, this finding may
      be obscured by a host of other patterns often identified in FMF. This includes
      basaloid folliculo-lymphoid hyperplasia, a granulomatous reaction, eosinophilic
      folliculitis, and follicular cystic changes with subtle atypical lymphocytes in
      the cyst wall. Follicular mucinosis (MF) and syringo-tropism are also variably
      present. Immunohistochemistry of all reported cases uniformly show a CD4+ T cell
      infiltrate. This review emphasizes and discusses the broad spectrum of histologic
      changes which may be seen in FMF, clues to the diagnosis, and some potential
      mimickers.

PMID- 19169214
TI  - Ekbom syndrome: a disease between dermatology and psychiatry.
AB  - The Ekbom syndrome or parasitosis delirium represents a rare mono-symptomatic
      psychosis characterized by the delirious firm belief of the patient, against all
      evidence, of being infested by cutaneous parasites. The syndrome affects in
      particular middle-aged women, and can be the single manifestation of
      psychological uneasiness or represent one of the aspects of a more complex
      psychiatric case, compromising almost totally any normal daily work and/or social
      activity. The authors present a recently observed clinical case and discuss the
      clinical-diagnostic and therapeutic aspects.

PMID- 19169215
TI  - Tinea capitis due to Trichophyton soudanense with a papular IDE reaction in
      Northern Italy.
AB  - A little boy from a Nigerian family who lives in a little industrialized village
      in the suburbs of Bergamo, (Northern Italy), has never been to his country but
      presented with tinea capitis and with a secondary papular pruritic eruption of
      the trunk. Fungal cultures analysis have shown the development of Trichophyton
      soudanense, an anthropophilic dermatophyte which is endemic in Africa, but only
      rarely reported in Italy and in other European countries. The growing racial
      mixing related to migratory movements is favoring, also in Italy, the integration
      of this strain with the species which are most commonly responsible for
      dermatophytoses and the appearance of papular IDE reactions which were only
      occasionally seen in the Italian children population.

PMID- 19169216
TI  - Hypothesis: can kojic acid prevent xanthelasma formation?

PMID- 19169217
TI  - Epidemiology of the cutaneous squamous cell carcinoma from 1981 to 2004.

PMID- 19169219
TI  - Missing heritability and GWAS utility.

PMID- 19169220
TI  - Body composition and physical function in older adults.

PMID- 19169221
TI  - Posttranslational modifications of PPAR-gamma: fine-tuning the metabolic master
      regulator.

PMID- 19169222
TI  - Adiponectin oligomers and ectopic fat in liver and skeletal muscle in humans.
AB  - We aimed at determining which circulating forms of the adipokine adiponectin that
      increases lipid oxidation in liver and skeletal muscle are related to ectopic fat
      in these depots in humans. Plasma total-, high-molecular weight (HMW)-, middle
      molecular weight (MMW)-, and low-molecular weight (LMW) adiponectin were
      quantified by an enzyme-linked immunosorbent assay. Their relationships with
      liver- and intramyocellular fat, measured using (1)H magnetic resonance
      spectroscopy, were investigated in 54 whites without type 2 diabetes. Liver fat,
      adjusted for gender, age, and total body fat, was associated only with HMW
      adiponectin (r = -0.35, P = 0.012), but not with total-, MMW-, or LMW
      adiponectin. In addition, subjects with fatty liver (liver fat > or =5.56%, n =
      15) had significantly lower HMW- (P = 0.04), but not total-, MMW-, or LMW
      adiponectin levels, compared to controls (n = 39). Similarly, intramyocellular
      fat correlated only with HMW (r = -0.32, P = 0.039), but not with the other
      circulating forms of adiponectin. These data indicate that, among circulating
      forms of adiponectin, HMW is strongly related to ectopic fat, thus possibly
      representing the form of adiponectin regulating lipid oxidation in liver and
      skeletal muscle.

PMID- 19169225
TI  - Amniotic membrane in ophthalmology: indications and limitations.
AB  - The amniotic membrane remains a useful tool in the treatment of several
      ophthalmic conditions, especially those related to the ocular surface. However,
      the 'success' reported in individual case reports and case series is not
      substantiated in the few published randomised controlled trials. More often than
      not, it is not as good as existing alternative options and, at best, is as good
      but with probably an increased cost. The variable outcomes could be related to
      inter and intra donor variations in the membrane and the depletion or alterations
      in its constituents subsequent to processing and storage. The membrane thus is a
      fairly 'non-standardised product' making comparisons of different applications
      and indications difficult. The potential for 'epidemic' infections, such as HIV,
      hepatitis B and C, is a serious issue as, in many parts of the world, fresh
      unquarantined membrane, at times with no tests for the above infectious agents,
      is being used. The exact mechanism of action of the membrane is not known but the
      consensus is that it acts as a substrate or scaffold for host cells to populate
      and thus facilitate healing and repair. The development of a standard 'synthetic
      membrane' using collagen or polymer matrices impregnated with putative beneficial
      ingredients, such as growth factors and antimicrobials, is being considered and
      may prove to be a step in the right direction.

PMID- 19169226
TI  - Surgical rehabilitation following severe ocular burns.
AB  - Chemical and thermal burns can cause devastating injuries to the anterior
      segment. The consequences of alkali injuries are notoriously severe due to the
      rapid penetration of these agents into the ocular tissues. Denaturation of
      tissue, inflammation, and scarring leads to loss of function. An understanding of
      the pathogenesis of tissue damage has lead to a rational approach to treatment.
      Emergency irrigation of the eye is essential and there is a 'window of
      opportunity' during the first 7-10 days after injury when medical treatment can
      significantly limit the potentially blinding consequences. The acute injury is
      followed by early and late reparative phases during which the prognosis can be
      further improved by surgical intervention. Early surgical intervention is
      targeted at protecting the ocular surface and encouraging re-epithelisation.
      Later, surgical treatments are directed at ocular surface reconstruction and
      restoration of vision. However, before any attempt is made at surface
      reconstruction, the ocular surface environment must be optimised by division of
      symblepharon, and correction of lid deformity and trichiasis. If there is
      conjunctivalisation of the corneal surface, limbal stem cell transplantation can
      restore a corneal epithelial cell phenotype, and transplantation of in
      vitroamplified corneal epithelial stem cells has been developed as an alternative
      to keratolimbal transfer techniques. Keratoplasty and cataract surgery may then
      be necessary to clear the visual axis. Finally, keratoprosthesis is an option for
      the most severely damaged eyes.

PMID- 19169227
TI  - Intravitreal VEGF levels in uveitis patients and treatment of uveitic macular
      oedema with intravitreal bevacizumab.
AB  - PURPOSE: Clinical data suggest a role for VEGF in uveitic cystoid macular oedema
      (CME), even though the data on intravitreal VEGF levels in these eyes is still
      inconclusive. We determined intravitreal VEGF levels and treated uveitis patients
      with intravitreal bevacizumab. METHODS: Intravitreal VEGF levels were measured in
      eight uveitis patients and 10 controls using cytometric bead array technology. In
      11 eyes of a second group of uveitis patients, CME was treated using 1.25 mg
      bevacizumab intravitreally. Re-injections of bevacizumab were given in patients
      showing a transient positive effect, defined as an increase of the best-corrected
      vision of at least two lines on a snellen chart. Alternatively, triamcinolone was
      given in patients, not responding to bevacizumab. RESULTS: Mean intravitreal VEGF
      concentration was 82.75+/-171.71 pg/ml (+/-SD) (range, 0.0-502.1 pg/ml), and
      below the detection levels in controls. A significant reduction of retinal
      thickness was seen at weeks 2 (P=0.001) and 4 (P=0.007). A significant
      improvement in VA was seen at week 2 (P=0.02). Patients presenting with a CME in
      baseline fluorescein-angiogram responded well towards bevacizumab treatment,
      unless an extensive leakage from the choroid or a leakage of the optic disk was
      detectable. In these patients, only intravitreally administered triamcinolone led
      to a reduction of the CME. CONCLUSIONS: Our data suggest that patients presenting
      with a diffuse leakage from the choroid in the fluorescein angiogram or an
      extensive leakage of the optic disk should be treated with intravitreal
      triamcinolone, whereas in patients presenting only a cystoid macular oedema
      bevacizumab treatment seems like a good choice.

PMID- 19169228
TI  - Pain relief during panretinal photocoagulation for diabetic retinopathy: a
      national survey.
AB  - AIMS: Panretinal photocoagulation (PRP) for proliferative retinopathy is known to
      be painful for some people; however, few studies have explored the effects of
      pain on the procedure within clinical practice. METHODS: This was a national
      survey of all Ophthalmic Units within the UK undertaken in late 2006. A
      questionnaire with 14 questions was developed, piloted, and sent to all NHS units
      in the UK. RESULTS: A 77% response rate was achieved. The vast majority of
      responses (96%) were from doctors. A large proportion (79%) of units see up to 20
      cases a week and most patients require up to 5 sessions of PRP. Eighty-eight
      percent said that the procedure is painful. Once present, pain can affect the
      number and strength of burns delivered and indirectly increases the number of
      sessions required to complete the therapy. Sub-tenons anaesthesia was the most
      commonly used analgesic and there is some tentative evidence to support its
      effect. Few units have a pre-emptive analgesic protocol. Some respondents were
      using laser with lower exposure and reported reduced pain. CONCLUSIONS: PRP is
      painful; however, most units do not deliver pain relief pre-emptively. There may
      be a case to support the routine use of sub-tenons anaesthesia until the full
      effects of new laser techniques become known.

PMID- 19169229
TI  - Replacement of the RPE monolayer.
AB  - There are numerous scenarios in which replacing the diseased RPE monolayer is an
      attractive but as yet unrealised goal. The proof of concept that vision can be
      improved by placing a healthy neuroretina onto a different, healthy, underlying
      RPE layer is demonstrated in patch graft transplantations. The surgical procedure
      to relocate the neuroretina is both complex and is hampered by postoperative
      complications and as such newer replacement procedures are also being
      investigated including stem cell replacement therapies. Past studies have largely
      focused on using cell suspensions and have had disappointing outcomes largely due
      to the lack of control over cellular differentiation, incomplete attachment onto
      Bruch's membrane and subsequent integration into the existing RPE monolayer. The
      choice of which cells to transplant is still under investigation and is
      complicated by factors such as the ease of collection of an adequate sample,
      rejection following implantation, the age of the cells and ethical issues. In all
      these situations, however, understanding the mechanisms of cellular
      differentiation are likely to be prerequisite to future successes.The current
      research into replacing the RPE monolayer is briefly discussed with reference to
      our experiences comparing IPE and RPE cells in an in vitro environment.

PMID- 19169230
TI  - Complement factor H gene polymorphisms and Chlamydia pneumoniae infection in age
      related macular degeneration.
AB  - PURPOSE: To investigate the association of the complement factor H gene
      (CFH)Y402H polymorphism and age-related macular degeneration (AMD) in the
      Austrian population (Caucasoid descent), and to determine whether there is an
      association between exposure to Chlamydia pneumoniae-responsible for up to 20% of
      community-acquired pneumoniae-and the AMD-associated CFHrisk polymorphism.
      METHODS: Genotypes were determined by polymerase chain reaction-restriction
      fragment length polymorphism analysis in 75 unrelated AMD patients and compared
      with 75 healthy, age-matched control subjects. C. pneumoniaeserum IgG was tested
      by ELISA (R&D) in both groups. The association between the CFHY402H genetic
      polymorphism and the disease was examined by chi (2)-test and logistic
      regression. RESULTS: CFH Y402H genotypefrequencies differed significantly between
      AMD patients and healthy controls (1277 TT, 22.7%; 1277 TC, 53.3%; and 1277 CC,
      22.7% in the AMD group; 1277 TT, 48.0%; 1277 TC, 38.7%; and 1277 CC, 13.3% in the
      control group) showing a P-value <0.005 (OR:2.920/3.811).No association was found
      between a positive C. pneumoniae titre and AMD (P=0.192), nor was any association
      found between C. pneumoniae and the CFH Y402H polymorphism. CONCLUSIONS: Our data
      confirm that the CFHY402H polymorphism is a risk factor for AMD in the Austrian
      population with a higher frequency of the Y402 polymorphism in AMD patients. No
      association between preceding C. pneumoniaeinfection and diagnosed AMD was found.

PMID- 19169231
TI  - Acute macular neuroretinopathy: anatomic localisation of the lesion with high
      resolution OCT.

PMID- 19169233
TI  - The use of Medpor-coated tear drainage tube in conjunctivodacryocystorhinostomy.

PMID- 19169232
TI  - Variations in five genes and the severity of age-related macular degeneration:
      results from the Muenster aging and retina study.
AB  - AIMS: Little is known about the role of genetic variants in the early stages of
      age-related macular degeneration (AMD). We aimed to investigate how genetic
      variations within five well-defined genes relate to AMD severity. METHODS: We
      analysed SNPs in the genes for complement factor H (CFH), age-related maculopathy
      susceptibility (ARMS2), HtrA serine peptidase 1 (HtrA1), complement factor B
      (CFB), and complement component 2 (C2)in 183 controls and 730 patients with
      increasing severity of AMD from the Muenster aging and retina study (MARS).
      Severity scoring was based on the Rotterdam classification of fundus photographs.
      RESULTS: Compared with controls, patients with very early AMD showed a
      significantly increased minor allele frequency (MAF) only for CFH-rs1061170. With
      increasing severity of AMD, SNPs in CFH-rs1061170,as well as ARMS2-rs10490924,
      became consistently more common (P<0.001). Likewise, HtrA1-rs11200638 was less
      clearly associated with AMD severity, whereas C2-rs9332739 and CFB-rs641153
      showed no relation. Multifactorial models confirmed CFH and ARMS2 as major
      determinants of AMD severity, whereas addition of HtrA1, C2 and CFB did not
      improve model prediction. In the models, age did not contribute to very early but
      to all more severe AMD stages, whereas smoking history had a significant impact
      only for late AMD. CONCLUSION: Our findings indicate that the CFH gene is
      involved in the onset of AMD, whereas both, the CFH and ARMS2 genes, and more
      weakly, the HtrA1 gene, appear to account for the advancement of AMD. The results
      for SNPs in the C2 and CFB genes were inconclusive. Genetic factors dominated in
      their impact over age and smoking history.

PMID- 19169234
TI  - Retinal pigment epithelium tear after intravitreal bevacizumab injection for
      polypoidal choroidal vasculopathy.

PMID- 19169235
TI  - Intravitreal bevacizumab for subfoveal choroidal neovascularization secondary to
      traumatic choroidal rupture.

PMID- 19169236
TI  - Management of diabetic retinopathy: could lipid-lowering be a worthwhile
      treatment modality?
AB  - Diabetic eye disease confers substantial burden on the patient quality of life.
      Current therapeutic strategies indicate an unmet clinical need for preventive
      therapy. Tight control of blood pressure and glycaemia are mandatory components
      of primary prevention strategies, but are insufficient to eliminate risk in all
      patients. A body of evidence supports a role for lipid-modifying therapy in
      reducing the diabetic retinopathy endpoints. Although inconclusive for statin
      therapy, results from the Fenofibrate Intervention and Event Lowering in Diabetes
      (FIELD) study show beneficial effects of fenofibrate in reducing the requirement
      for laser therapy, and particularly in preventing disease progression in patients
      with pre-existing diabetic retinopathy. However, there is a need for confirmation
      of these findings in large prospective studies with progression of retinopathy as
      the primary endpoint, such as the ACCORD-EYE (Action to Control Cardiovascular
      Risk in Diabetes-EYE) study, and in a clinical trial specifically conducted for
      diabetic maculopathy. In addition, elucidation of the mechanism(s) of effect of
      fenofibrate is indicated.

PMID- 19169237
TI  - Patching retinal breaks with Seprafilm in experimental rhegmatogenous retinal
      detachment of rabbit eyes.
AB  - PURPOSE: To examine the short-term effect of Seprafilm for patching retinal
      breaks in experimental rhegmatogenous retinal detachment of rabbit eyes. METHODS:
      Experimental retinal detachment with a break was made and repaired by fluid-gas
      exchange during vitreous surgery in 10 rabbit eyes. In seven eyes, Seprafilm was
      applied to cover iatrogenic retinal breaks entirely (study group) and in other
      three eyes operations were finished without Seprafilm application (control
      group). Funduscopic examination was carried out in both groups and in study group
      optical coherence tomography (OCT) was performed to observe Seprafilm on the
      retinal break. Eyes of study group were enucleated on 7th and 14th postoperative
      day for histological evaluation. RESULTS: The funduscopic examination showed that
      the retina was reattached in all eyes of study group. Meanwhile all three eyes of
      control group resulted in proliferative vitreoretinopathy. OCT showed that
      Seprafilm adhered to the retina tightly. Funduscopic examination and OCT showed
      Seprafilm dissolved within 14 days. Histological examination revealed that
      Seprafilm adhered tightly to the retina and there was no inflammatory change at
      the Seprafilm application sites. CONCLUSIONS: In our small number of this study,
      Seprafilm was found to be beneficial to patch small and posteriorly located
      retinal breaks in vitreous surgery for rhegmatogenous retinal detachment.

PMID- 19169238
TI  - 23-Gauge transconjunctival sutureless pars plana vitrectomy: results of a
      prospective study.
AB  - PURPOSE: To evaluate results of 23-gauge transconjunctival sutureless vitrectomy
      in various indications of vitreoretinal diseases. DESIGN: Prospective, non
      comparative study. MATERIALS AND METHODS: Fifty-seven consecutive eyes of 57
      patients underwent vitreoretinal surgery by one surgeon using the 23-gauge, two
      step instrumentation developed by Dutch Ophthalmic Research Center Inc., for
      epiretinal membranes (n=24), macular holes (n=10), diabetic retinopathy (n=4),
      rhegmatogenous retinal detachment (n=3), silicone oil removal (n=10), and other
      procedures (n=4). Mean operative time and intraoperative and postoperative
      complications were recorded. At 1 month, postoperative visual acuity, anatomical
      results, and induced astigmatism measured by Orbscan (BAUSCH and LOMB
      laboratories Inc., Rochester, NY, USA) were analysed. RESULTS: Mean operative
      time was 32.6+/-21.5 min. At 1 month, mean visual acuity improved from 1.09+/
      0.82 to 0.80+/-0.79 logMar. Transient postoperative hypotony was the most common
      complication (21.1%), resolving without treatment. There was no choroidal
      effusion; and no postoperative endophthalmitis was observed. There were no
      significant changes in mean keratometry (P=0.957), mean axis (P=0.818), and power
      of astigmatism (P=0.860) at 1 month. CONCLUSIONS: A 23-gauge vitrectomy seems to
      be safe and effective for a wide range of indications for vitreoretinal surgery.
      Further studies are needed to compare it with 25-gauge and 20-gauge vitrectomy in
      larger series.

PMID- 19169239
TI  - Randomised clinical trial of intravitreal Avastin vs photodynamic therapy and
      intravitreal triamcinolone: long-term results.
AB  - PURPOSE: To compare 1-year functional and anatomic outcomes of intravitreal
      bevacizumab (IVB) and photodynamic therapy plus intravitreal triamcinolone
      (PDT+IVTA) combination in patients with neovascular age-related macular
      degeneration (AMD). METHODS: In this prospective, randomised, controlled clinical
      trial, 28 patients were included. All patients were randomised 1 : 1 to 0.04 ml/1
      mg of IVB or PDT plus same day 0.1 ml/4 mg IVTA (PDT+IVTA). Follow-up
      examinations were performed in monthly intervals in IVB group and every 3 months
      in PDT+IVTA group. Main outcomes were change in mean visual acuity (VA), mean
      central retinal thickness (CRT) and the mean number of treatments. RESULTS: At
      month 12, mean VA improved to a 1.5-line gain in IVB group, and lost three
      letters in PDT+IVTA group (P=0.02). Mean CRT was reduced from 357 microm at
      baseline to 244 microm at month 12 in IVB group and from 326 microm to 254
      microm, respectively, in PDT+IVTA group (P=0.8). The mean number of treatments
      was 6.8 in the IVB group vs 1.9 in the PDT+IVTA group. No significant local or
      systemic safety concerns were detected during follow-up time. CONCLUSIONS:
      Patients treated with IVB showed a significant better VA outcome compared with
      the PDT+IVTA group despite the fact that both modalities showed equal potency in
      reducing CRT during a 12-month period.

PMID- 19169240
TI  - Coenzyme recognition and gene regulation by a flavin mononucleotide riboswitch.
AB  - The biosynthesis of several protein cofactors is subject to feedback regulation
      by riboswitches. Flavin mononucleotide (FMN)-specific riboswitches, also known as
      RFN elements, direct expression of bacterial genes involved in the biosynthesis
      and transport of riboflavin (vitamin B(2)) and related compounds. Here we present
      the crystal structures of the Fusobacterium nucleatum riboswitch bound to FMN,
      riboflavin and antibiotic roseoflavin. The FMN riboswitch structure, centred on
      an FMN-bound six-stem junction, does not fold by collinear stacking of adjacent
      helices, typical for folding of large RNAs. Rather, it adopts a butterfly-like
      scaffold, stapled together by opposingly directed but nearly identically folded
      peripheral domains. FMN is positioned asymmetrically within the junctional site
      and is specifically bound to RNA through interactions with the isoalloxazine ring
      chromophore and direct and Mg(2+)-mediated contacts with the phosphate moiety.
      Our structural data, complemented by binding and footprinting experiments, imply
      a largely pre-folded tertiary RNA architecture and FMN recognition mediated by
      conformational transitions within the junctional binding pocket. The inherent
      plasticity of the FMN-binding pocket and the availability of large openings make
      the riboswitch an attractive target for structure-based design of FMN-like
      antimicrobial compounds. Our studies also explain the effects of spontaneous and
      antibiotic-induced deregulatory mutations and provided molecular insights into
      FMN-based control of gene expression in normal and riboflavin-overproducing
      bacterial strains.

PMID- 19169241
TI  - Post-transcriptional processing generates a diversity of 5'-modified long and
      short RNAs.
AB  - The transcriptomes of eukaryotic cells are incredibly complex. Individual non
      coding RNAs dwarf the number of protein-coding genes, and include classes that
      are well understood as well as classes for which the nature, extent and
      functional roles are obscure. Deep sequencing of small RNAs (<200 nucleotides)
      from human HeLa and HepG2 cells revealed a remarkable breadth of species. These
      arose both from within annotated genes and from unannotated intergenic regions.
      Overall, small RNAs tended to align with CAGE (cap-analysis of gene expression)
      tags, which mark the 5' ends of capped, long RNA transcripts. Many small RNAs,
      including the previously described promoter-associated small RNAs, appeared to
      possess cap structures. Members of an extensive class of both small RNAs and CAGE
      tags were distributed across internal exons of annotated protein coding and non
      coding genes, sometimes crossing exon-exon junctions. Here we show that
      processing of mature mRNAs through an as yet unknown mechanism may generate
      complex populations of both long and short RNAs whose apparently capped 5' ends
      coincide. Supplying synthetic promoter-associated small RNAs corresponding to the
      c-MYC transcriptional start site reduced MYC messenger RNA abundance. The studies
      presented here expand the catalogue of cellular small RNAs and demonstrate a
      biological impact for at least one class of non-canonical small RNAs.

PMID- 19169242
TI  - Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid
      leukaemia.
AB  - Although the role of Hedgehog (Hh) signalling in embryonic pattern formation is
      well established, its functions in adult tissue renewal and maintenance remain
      unclear, and the relationship of these functions to cancer development has not
      been determined. Here we show that the loss of Smoothened (Smo), an essential
      component of the Hh pathway, impairs haematopoietic stem cell renewal and
      decreases induction of chronic myelogenous leukaemia (CML) by the BCR-ABL1
      oncoprotein. Loss of Smo causes depletion of CML stem cells--the cells that
      propagate the leukaemia--whereas constitutively active Smo augments CML stem cell
      number and accelerates disease. As a possible mechanism for Smo action, we show
      that the cell fate determinant Numb, which depletes CML stem cells, is increased
      in the absence of Smo activity. Furthermore, pharmacological inhibition of Hh
      signalling impairs not only the propagation of CML driven by wild-type BCR-ABL1,
      but also the growth of imatinib-resistant mouse and human CML. These data
      indicate that Hh pathway activity is required for maintenance of normal and
      neoplastic stem cells of the haematopoietic system and raise the possibility that
      the drug resistance and disease recurrence associated with imatinib treatment of
      CML might be avoided by targeting this essential stem cell maintenance pathway.

PMID- 19169243
TI  - Bidirectional promoters generate pervasive transcription in yeast.
AB  - Genome-wide pervasive transcription has been reported in many eukaryotic
      organisms, revealing a highly interleaved transcriptome organization that
      involves hundreds of previously unknown non-coding RNAs. These recently
      identified transcripts either exist stably in cells (stable unannotated
      transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway
      (cryptic unstable transcripts, CUTs). One characteristic of pervasive
      transcription is the extensive overlap of SUTs and CUTs with previously annotated
      features, which prompts questions regarding how these transcripts are generated,
      and whether they exert function. Single-gene studies have shown that
      transcription of SUTs and CUTs can be functional, through mechanisms involving
      the generated RNAs or their generation itself. So far, a complete transcriptome
      architecture including SUTs and CUTs has not been described in any organism.
      Knowledge about the position and genome-wide arrangement of these transcripts
      will be instrumental in understanding their function. Here we provide a
      comprehensive analysis of these transcripts in the context of multiple
      conditions, a mutant of the exosome machinery and different strain backgrounds of
      Saccharomyces cerevisiae. We show that both SUTs and CUTs display distinct
      patterns of distribution at specific locations. Most of the newly identified
      transcripts initiate from nucleosome-free regions (NFRs) associated with the
      promoters of other transcripts (mostly protein-coding genes), or from NFRs at the
      3' ends of protein-coding genes. Likewise, about half of all coding transcripts
      initiate from NFRs associated with promoters of other transcripts. These data
      change our view of how a genome is transcribed, indicating that bidirectionality
      is an inherent feature of promoters. Such an arrangement of divergent and
      overlapping transcripts may provide a mechanism for local spreading of regulatory
      signals-that is, coupling the transcriptional regulation of neighbouring genes by
      means of transcriptional interference or histone modification.

PMID- 19169244
TI  - Widespread bidirectional promoters are the major source of cryptic transcripts in
      yeast.
AB  - Pervasive and hidden transcription is widespread in eukaryotes, but its global
      level, the mechanisms from which it originates and its functional significance
      are unclear. Cryptic unstable transcripts (CUTs) were recently described as a
      principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae.
      These transcripts are targeted for degradation immediately after synthesis by the
      action of the Nrd1-exosome-TRAMP complexes. Although CUT degradation mechanisms
      have been analysed in detail, the genome-wide distribution at the nucleotide
      resolution and the prevalence of CUTs are unknown. Here we report the first high
      resolution genomic map of CUTs in yeast, revealing a class of potentially
      functional CUTs and the intrinsic bidirectional nature of eukaryotic promoters.
      An RNA fraction highly enriched in CUTs was analysed by a 3' Long-SAGE (serial
      analysis of gene expression) approach adapted to deep sequencing. The resulting
      detailed genomic map of CUTs revealed that they derive from extremely widespread
      and very well defined transcription units and do not result from unspecific
      transcriptional noise. Moreover, the transcription of CUTs predominantly arises
      within nucleosome-free regions, most of which correspond to promoter regions of
      bona fide genes. Some of the CUTs start upstream from messenger RNAs and overlap
      their 5' end. Our study of glycolysis genes, as well as recent results from the
      literature, indicate that such concurrent transcription is potentially associated
      with regulatory mechanisms. Our data reveal numerous new CUTs with such a
      potential regulatory role. However, most of the identified CUTs corresponded to
      transcripts divergent from the promoter regions of genes, indicating that they
      represent by-products of divergent transcription occurring at many and possibly
      most promoters. Eukaryotic promoter regions are thus intrinsically bidirectional,
      a fundamental property that escaped previous analyses because in most cases
      divergent transcription generates short-lived unstable transcripts present at
      very low steady-state levels.

PMID- 19169245
TI  - Prediction of high-responding peptides for targeted protein assays by mass
      spectrometry.
AB  - Protein biomarker discovery produces lengthy lists of candidates that must
      subsequently be verified in blood or other accessible biofluids. Use of targeted
      mass spectrometry (MS) to verify disease- or therapy-related changes in protein
      levels requires the selection of peptides that are quantifiable surrogates for
      proteins of interest. Peptides that produce the highest ion-current response
      (high-responding peptides) are likely to provide the best detection sensitivity.
      Identification of the most effective signature peptides, particularly in the
      absence of experimental data, remains a major resource constraint in developing
      targeted MS-based assays. Here we describe a computational method that uses
      protein physicochemical properties to select high-responding peptides and
      demonstrate its utility in identifying signature peptides in plasma, a complex
      proteome with a wide range of protein concentrations. Our method, which employs a
      Random Forest classifier, facilitates the development of targeted MS-based assays
      for biomarker verification or any application where protein levels need to be
      measured.

PMID- 19169246
TI  - Shear-induced anisotropic plastic flow from body-centred-cubic tantalum before
      melting.
AB  - There are many structural and optical similarities between a liquid and a plastic
      flow. Thus, it is non-trivial to distinguish between them at high pressures and
      temperatures, and a detailed description of the transformation between these
      phenomena is crucial to our understanding of the melting of metals at high
      pressures. Here we report a shear-induced, partially disordered viscous plastic
      flow from body-centred-cubic tantalum under heating before it melts into a
      liquid. This thermally activated structural transformation produces a unique, one
      dimensional structure analogous to a liquid crystal with the rheological
      characteristics of Bingham plastics. This mechanism is not specific to Ta and is
      expected to hold more generally for other metals. Remarkably, this transition is
      fully consistent with the previously reported anomalously low-temperature melting
      curve and thus offers a plausible resolution to a long-standing controversy about
      melting of metals under high pressures.

PMID- 19169247
TI  - Conduction at domain walls in oxide multiferroics.
AB  - Domain walls may play an important role in future electronic devices, given their
      small size as well as the fact that their location can be controlled. Here, we
      report the observation of room-temperature electronic conductivity at
      ferroelectric domain walls in the insulating multiferroic BiFeO(3). The origin
      and nature of the observed conductivity are probed using a combination of
      conductive atomic force microscopy, high-resolution transmission electron
      microscopy and first-principles density functional computations. Our analyses
      indicate that the conductivity correlates with structurally driven changes in
      both the electrostatic potential and the local electronic structure, which shows
      a decrease in the bandgap at the domain wall. Additionally, we demonstrate the
      potential for device applications of such conducting nanoscale features.

PMID- 19169248
TI  - Ternary Pt/Rh/SnO2 electrocatalysts for oxidizing ethanol to CO2.
AB  - Ethanol, with its high energy density, likely production from renewable sources
      and ease of storage and transportation, is almost the ideal combustible for fuel
      cells wherein its chemical energy can be converted directly into electrical
      energy. However, commercialization of direct ethanol fuel cells has been impeded
      by ethanol's slow, inefficient oxidation even at the best electrocatalysts. We
      synthesized a ternary PtRhSnO(2)/C electrocatalyst by depositing platinum and
      rhodium atoms on carbon-supported tin dioxide nanoparticles that is capable of
      oxidizing ethanol with high efficiency and holds great promise for resolving the
      impediments to developing practical direct ethanol fuel cells. This
      electrocatalyst effectively splits the C-C bond in ethanol at room temperature in
      acid solutions, facilitating its oxidation at low potentials to CO(2), which has
      not been achieved with existing catalysts. Our experiments and density functional
      theory calculations indicate that the electrocatalyst's activity is due to the
      specific property of each of its constituents, induced by their interactions.
      These findings help explain the high activity of Pt-Ru for methanol oxidation and
      the lack of it for ethanol oxidation, and point to the way to accomplishing the C
      C bond splitting in other catalytic processes.

PMID- 19169249
TI  - UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5
      signaling pathways.
AB  - The UNC-5 receptor mediates axon repulsion from UNC-6/netrin through UNC-40
      dependent (UNC-5 + UNC-40) and independent (UNC-5 alone) signaling pathways. It
      has been shown that UNC-40-dependent signaling is required for long-range
      repulsion of UNC-6/netrin; however, the mechanisms used to regulate distinct UNC
      5 signaling pathways are poorly understood. We found that the C. elegans
      transforming growth factor beta (TGF-beta) family ligand UNC-129, graded opposite
      to UNC-6/netrin, functions independent of the canonical TGF-beta receptors to
      regulate UNC-5 cellular responses. Our observations indicates that UNC-129
      facilitates long-range repulsive guidance of UNC-6 by enhancing UNC-5 + UNC-40
      signaling at the expense of UNC-5 alone signaling through interaction with the
      UNC-5 receptor. This increases the set point sensitivity of growth cones to UNC
      6/netrin as they simultaneously migrated up the UNC-129 gradient and down the UNC
      6 gradient. Similar regulatory interactions between oppositely graded
      extracellular cues may be a common theme in guided cell and axon migrations.

PMID- 19169250
TI  - A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA
      receptors.
AB  - The endocytosis of AMPA receptors (AMPARs) underlies several forms of synaptic
      plasticity, including NMDA receptor (NMDAR)-dependent long-term depression (LTD),
      but the molecular mechanisms responsible for this trafficking remain unknown. We
      found that PSD-95, a major postsynaptic density protein, is important for NMDAR
      triggered endocytosis of synaptic AMPARs in rat neuron cultures because of its
      binding to A kinase-anchoring protein 150 (AKAP150), a scaffold for specific
      protein kinases and phosphatases. Knockdown of PSD-95 with shRNA blocked NMDAR
      triggered, but not constitutive or mGluR-triggered, endocytosis of AMPARs.
      Deletion of PSD-95's Src homology 3 and guanylate kinase-like domains, as well as
      a point mutation (L460P), both of which inhibit binding of PSD-95 to AKAP150,
      also blocked NMDAR-triggered AMPAR endocytosis. Furthermore, expression of a
      mutant AKAP150 that does not bind calcineurin inhibited this NMDAR-triggered
      trafficking event. Our results suggest that PSD-95's interaction with AKAP150 is
      critical for NMDAR-triggered AMPAR endocytosis and LTD, possibly because these
      scaffolds position calcineurin in the appropriate subsynaptic domain.

PMID- 19169251
TI  - A chloride conductance in VGLUT1 underlies maximal glutamate loading into
      synaptic vesicles.
AB  - Uptake of glutamate into synaptic vesicles is mediated by vesicular glutamate
      transporters (VGLUTs). Although glutamate uptake has been shown to depend
      critically on Cl(-), the precise contribution of this ion to the transport
      process is unclear. We found that VGLUT1, and not ClC-3 as proposed previously,
      represents the major Cl(-) permeation pathway in synaptic vesicles. Using
      reconstituted VGLUT1, we found that the biphasic dependence of glutamate
      transport on extravesicular Cl(-) is a result of the permeation of this anion
      through VGLUT1 itself. Moreover, we observed that high luminal Cl(-)
      concentrations markedly enhanced loading of glutamate by facilitation of membrane
      potential-driven uptake and discovered a hitherto unrecognized transport mode of
      VGLUT1. Because a steep Cl(-) gradient across the synaptic vesicle membrane
      exists in endocytosed synaptic vesicles, our results imply that the transport
      velocity and the final glutamate content are highly influenced, if not
      determined, by the extracellular Cl(-) concentration.

PMID- 19169252
TI  - Dopamine modulates an mGluR5-mediated depolarization underlying prefrontal
      persistent activity.
AB  - The intrinsic properties of neurons that enable them to maintain depolarized,
      persistently activated states in the absence of sustained input are poorly
      understood. In short-term memory tasks, individual prefrontal cortical (PFC)
      neurons can maintain persistent action potential output during delay periods
      between informative cues and behavioral responses. Dopamine and drugs of abuse
      alter PFC function and working memory, possibly by modulating intrinsic neuronal
      properties. Here we used patch-clamp recording of layer 5 PFC pyramidal neurons
      to identify a postsynaptic depolarization that was evoked by action potential
      bursts and mediated by metabotropic glutamate receptor 5 (mGluR5). This
      depolarization occurred in the absence of recurrent synaptic activity and was
      reduced by a dopamine D1 receptor (D1R) protein kinase A pathway. After
      behavioral sensitization to cocaine, the depolarization was substantially
      diminished and D1R modulation was lost. We propose that burst-evoked intrinsic
      depolarization is a form of short-term cellular memory that is modulated by
      dopamine and cocaine experience.

PMID- 19169253
TI  - Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility
      factor for psoriasis.
AB  - Psoriasis is a common inflammatory skin disease with a prevalence of 2-3% in
      individuals of European ancestry. In a genome-wide search for copy number
      variants (CNV) using a sample pooling approach, we have identified a deletion
      comprising LCE3B and LCE3C, members of the late cornified envelope (LCE) gene
      cluster. The absence of LCE3B and LCE3C (LCE3C_LCE3B-del) is significantly
      associated (P = 1.38E-08) with risk of psoriasis in 2,831 samples from Spain, The
      Netherlands, Italy and the United States, and in a family-based study (P = 5.4E
      04). LCE3C_LCE3B-del is tagged by rs4112788 (r(2) = 0.93), which is also strongly
      associated with psoriasis (P < 6.6E-09). LCE3C_LCE3B-del shows epistatic effects
      with the HLA-Cw6 allele on the development of psoriasis in Dutch samples and
      multiplicative effects in the other samples. LCE expression can be induced in
      normal epidermis by skin barrier disruption and is strongly expressed in
      psoriatic lesions, suggesting that compromised skin barrier function has a role
      in psoriasis susceptibility.

PMID- 19169254
TI  - Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB
      pathways.
AB  - Psoriasis is a common immune-mediated disorder that affects the skin, nails and
      joints. To identify psoriasis susceptibility loci, we genotyped 438,670 SNPs in
      1,409 psoriasis cases and 1,436 controls of European ancestry. We followed up 21
      promising SNPs in 5,048 psoriasis cases and 5,041 controls. Our results provide
      strong support for the association of at least seven genetic loci and psoriasis
      (each with combined P < 5 x 10(-8)). Loci with confirmed association include HLA
      C, three genes involved in IL-23 signaling (IL23A, IL23R, IL12B), two genes that
      act downstream of TNF-alpha and regulate NF-kappaB signaling (TNIP1, TNFAIP3) and
      two genes involved in the modulation of Th2 immune responses (IL4, IL13).
      Although the proteins encoded in these loci are known to interact biologically,
      we found no evidence for epistasis between associated SNPs. Our results expand
      the catalog of genetic loci implicated in psoriasis susceptibility and suggest
      priority targets for study in other auto-immune disorders.

PMID- 19169256
TI  - System-wide molecular evidence for phenotypic buffering in Arabidopsis.
AB  - We profiled 162 lines of Arabidopsis for variation in transcript, protein and
      metabolite abundance using mRNA microarrays, two-dimensional polyacrylamide gel
      electrophoresis, gas chromatography time-of-flight mass spectrometry, liquid
      chromatography quadrupole time-of-flight mass spectrometry, and proton nuclear
      magnetic resonance. We added all publicly available phenotypic data from the same
      lines and mapped quantitative trait loci (QTL) for 40,580 molecular and 139
      phenotypic traits. We found six QTL hot spots with major, system-wide effects,
      suggesting there are six breakpoints in a system otherwise buffered against many
      of the 500,000 SNPs.

PMID- 19169255
TI  - Psoriasis genome-wide association study identifies susceptibility variants within
      LCE gene cluster at 1q21.
AB  - We report the first large genome-wide association study (GWAS) in a Chinese
      population to identify susceptibility variants for psoriasis using a two-stage
      case-control design. In the first stage, we carried out a genome-wide association
      analysis in 1,139 cases and 1,132 controls of Chinese Han ancestry using Illumina
      Human 610-Quad BeadChips. In the second stage, we took top SNPs forward for
      replication in two independent samples of 5,182 cases and 6,516 controls of
      Chinese Han ancestry, and 539 cases and 824 controls of Chinese Uygur ancestry.
      In addition to the strong replication for two known susceptibility loci MHC
      (rs1265181, P = 1.93 x 10(-208), OR = 22.62) and IL12B (rs3213094, P(combined) =
      2.58 x 10(-26), OR = 0.78), we identified a new susceptibility locus within the
      LCE gene cluster on 1q21 (rs4085613, P(combined) = 6.69 x 10(-30), OR = 0.76).

PMID- 19169257
TI  - Polyubiquitin substrates allosterically activate their own degradation by the 26S
      proteasome.
AB  - The 26S proteasome degrades polyubiquitylated (polyUb) proteins by an ATP
      dependent mechanism. Here we show that binding of model polyUb substrates to the
      19S regulator of mammalian and yeast 26S proteasomes enhances the peptidase
      activities of the 20S proteasome about two-fold in a process requiring ATP
      hydrolysis. Monoubiquitylated proteins or tetraubiquitin alone exert no effect.
      However, 26S proteasomes from the yeast alpha3DeltaN open-gate mutant and the
      rpt2YA and rpt5YA mutants with impaired gating can still be activated
      (approximately 1.3-fold to 1.8-fold) by polyUb-protein binding. Thus, binding of
      polyUb substrates to the 19S regulator stabilizes gate opening of the 20S
      proteasome and induces conformational changes of the 20S proteasome that
      facilitate channeling of substrates and their access to active sites. In
      consequence, polyUb substrates will allosterically stimulate their own
      degradation.

PMID- 19169258
TI  - Recognition of atypical 5' splice sites by shifted base-pairing to U1 snRNA.
AB  - Accurate pre-mRNA splicing is crucial for gene expression. The 5' splice site (5'
      ss)--the highly diverse element at the 5' end of introns--is initially recognized
      via base-pairing to the 5' end of the U1 small nuclear RNA (snRNA). However, many
      natural 5' ss have a poor match to the consensus sequence, and are predicted to
      be weak. Using genetic suppression experiments in human cells, we demonstrate
      that some atypical 5' ss are actually efficiently recognized by U1, in an
      alternative base-pairing register that is shifted by one nucleotide. These
      atypical 5' ss are phylogenetically widespread, and many of them are conserved.
      Moreover, shifted base-pairing provides an explanation for the effect of a 5' ss
      mutation associated with pontocerebellar hypoplasia. The unexpected flexibility
      in 5' ss-U1 base-pairing challenges an established paradigm and has broad
      implications for splice-site prediction algorithms and gene-annotation efforts in
      genome projects.

PMID- 19169259
TI  - Photoactivatable mCherry for high-resolution two-color fluorescence microscopy.
AB  - The reliance of modern microscopy techniques on photoactivatable fluorescent
      proteins prompted development of mCherry variants that are initially dark but
      become red fluorescent after violet-light irradiation. Using ensemble and single
      molecule characteristics as selection criteria, we developed PAmCherry1 with
      excitation/emission maxima at 564/595 nm. Compared to other monomeric red
      photoactivatable proteins, it has faster maturation, better pH stability, faster
      photoactivation, higher photoactivation contrast and better photostability. Lack
      of green fluorescence and single-molecule behavior make monomeric PAmCherry1 a
      preferred tag for two-color diffraction-limited photoactivation imaging and for
      super-resolution techniques such as one- and two-color photoactivated
      localization microscopy (PALM). We performed PALM imaging using PAmCherry1-tagged
      transferrin receptor expressed alone or with photoactivatable GFP-tagged clathrin
      light chain. Pair correlation and cluster analyses of the resulting PALM images
      identified < or =200 nm clusters of transferrin receptor and clathrin light chain
      at < or =25 nm resolution and confirmed the utility of PAmCherry1 as an
      intracellular probe.

PMID- 19169260
TI  - A bright and photostable photoconvertible fluorescent protein.
AB  - Photoconvertible fluorescent proteins are potential tools for investigating
      dynamic processes in living cells and for emerging super-resolution microscopy
      techniques. Unfortunately, most probes in this class are hampered by
      oligomerization, small photon budgets or poor photostability. Here we report an
      EosFP variant that functions well in a broad range of protein fusions for dynamic
      investigations, exhibits high photostability and preserves the approximately 10
      nm localization precision of its parent.

PMID- 19169261
TI  - Regulation of lymphoid versus myeloid fate 'choice' by the transcription factor
      Mef2c.
AB  - Despite advances in the identification of lymphoid-restricted progenitor cells,
      the transcription factors essential for their generation remain to be identified.
      Here we describe an unexpected function for the myeloid oncogene product Mef2c in
      lymphoid development. Mef2c deficiency was associated with profound defects in
      the production of B cells, T cells, natural killer cells and common lymphoid
      progenitor cells and an enhanced myeloid output. In multipotent progenitors,
      Mef2c was required for the proper expression of several key lymphoid regulators
      and restriction of the myeloid fate. Our studies also show that Mef2c was a
      critical transcriptional target of the transcription factor PU.1 during
      lymphopoiesis. Thus, Mef2c is a crucial component of the transcriptional network
      that regulates cell fate 'choice' in multipotent progenitors.

PMID- 19169262
TI  - The gene encoding early growth response 2, a target of the transcription factor
      NFAT, is required for the development and maturation of natural killer T cells.
AB  - The influence of signals transmitted by the phosphatase calcineurin and the
      transcription factor NFAT on the development and function of natural killer T
      (NKT) cells is unclear. In this report, we demonstrate that the transcription
      factor early growth response 2 (Egr2), a target gene of NFAT, was specifically
      required for the ontogeny of NKT cells but not that of conventional CD4(+) or
      CD8(+) T cells. NKT cells developed normally in the absence of Egr1 or Egr3,
      which suggests that Egr2 is a specific regulator of NKT cell differentiation. We
      found that Egr2 was important in the selection, survival and maturation of NKT
      cells. Our findings emphasize the importance of the calcineurin-NFAT-Egr2 pathway
      in the development of the NKT lymphocyte lineage.

PMID- 19169263
TI  - Regulatory T cells are key cerebroprotective immunomodulators in acute
      experimental stroke.
AB  - Systemic and local inflammatory processes have a key, mainly detrimental role in
      the pathophysiology of ischemic stroke. Currently, little is known about
      endogenous counterregulatory immune mechanisms. We examined the role of the key
      immunomodulators CD4(+)CD25(+) forkhead box P3 (Foxp3)(+) regulatory T
      lymphocytes (T(reg) cells), after experimental brain ischemia. Depletion of
      T(reg) cells profoundly increased delayed brain damage and deteriorated
      functional outcome. Absence of T(reg) cells augmented postischemic activation of
      resident and invading inflammatory cells including microglia and T cells, the
      main sources of deleterious cerebral tumor necrosis factor-alpha (TNF-alpha) and
      interferon-gamma (IFN-gamma), respectively. Early antagonization of TNF-alpha and
      delayed neutralization of IFN-gamma prevented infarct growth in T(reg) cell
      depleted mice. Intracerebral interleukin-10 (IL-10) substitution abrogated the
      cytokine overexpression after T(reg) cell depletion and prevented secondary
      infarct growth, whereas transfer of IL-10-deficient T(reg) cells in an adoptive
      transfer model was ineffective. In conclusion, T(reg) cells are major
      cerebroprotective modulators of postischemic inflammatory brain damage targeting
      multiple inflammatory pathways. IL-10 signaling is essential for their
      immunomodulatory effect.

PMID- 19169264
TI  - De novo expression of Trpm4 initiates secondary hemorrhage in spinal cord injury.
AB  - The role of transient receptor potential M4 (Trpm4), an unusual member of the Trp
      family of ion channels, is poorly understood. Using rodent models of spinal cord
      injury, we studied involvement of Trpm4 in the progressive expansion of secondary
      hemorrhage associated with capillary fragmentation, the most destructive
      mechanism of secondary injury in the central nervous system. Trpm4 mRNA and
      protein were abundantly upregulated in capillaries preceding their fragmentation
      and formation of petechial hemorrhages. Trpm4 expression in vitro rendered COS-7
      cells highly susceptible to oncotic swelling and oncotic death following ATP
      depletion. After spinal cord injury, in vivo gene suppression in rats treated
      with Trpm4 antisense or in Trpm4(-/-) mice preserved capillary structural
      integrity, eliminated secondary hemorrhage, yielded a threefold to fivefold
      reduction in lesion volume and produced a substantial improvement in neurological
      function. To our knowledge, this is the first example of a Trp channel that must
      undergo de novo expression for manifestation of central nervous system pathology.

PMID- 19169265
TI  - Antioxidant effects of D-004, a lipid extract from the Roystonea regia fruit, on
      the plasma of healthy men.
AB  - The aim of this study was to conduct a randomized, double-blind and placebo
      controlled study to investigate the effects of D-004, a lipid extract of the
      Roystonea regia fruit that prevents testosterone- and phenylepinephrine-induced
      prostate hyperplasia in rodents, on plasma oxidative markers in healthy men. We
      enrolled male volunteers (20-55 years) in good health and without lower urinary
      tract symptoms. Thirty-four eligible participants were randomized to placebo or D
      004 (320 mg) capsules administered daily for 6 weeks. An interim check-up and a
      final visit were conducted after 3 and 6 weeks of therapy, respectively. Physical
      examinations were performed at each visit, and laboratory tests were performed at
      baseline and at treatment completion. Oxidative variables included plasma
      malondialdehyde (MDA), total hydroxyperoxides (TOH), sulphydryl (SH) groups and
      total antioxidant status (TAS). We assessed treatment compliance and addressed
      adverse experiences (AEs) at weeks 3 and 6. At week 6, with D-004, the mean
      reductions of plasma MDA (26.7%), TOH (18.8%) and SH groups (31.6%), and the mean
      increase of TAS (35.3%) were significantly different from those of placebo
      (P<0.001 for plasma TAS, P<0.0001 for all other comparisons). D-004 did not
      differ from the placebo in safety indicators. There were two withdrawals (both in
      the D-004 group), with one due to dyspepsia (the only AE during the trial). In
      conclusion, D-004 displayed antioxidant effects on plasma oxidative markers in
      healthy men, which was consistent with findings from laboratory experimental
      studies.

PMID- 19169266
TI  - Testosterone alleviates tumor necrosis factor-alpha-mediated tissue factor
      pathway inhibitor downregulation via suppression of nuclear factor-kappa B in
      endothelial cells.
AB  - We have observed earlier that testosterone at physiological concentrations can
      stimulate tissue factor pathway inhibitor (TFPI) gene expression through the
      androgen receptor in endothelial cells. This study further investigated the
      impact of testosterone on TFPI levels in response to inflammatory cytokine tumor
      necrosis factor-alpha (TNF-alpha). Cultured human umbilical vein endothelial
      cells were incubated in the presence or absence of testosterone or TNF-alpha.
      TFPI protein and mRNA levels were assessed by enzyme-linked immunosorbent assay
      and quantitative real-time reverse transcription polymerase chain reaction. To
      study the cellular mechanism of testosterone's action, nuclear factor-kappa B (NF
      kappaB) translocation was confirmed by electrophoretic mobility shift assays. We
      found that after NF-kappaB was activated by TNF-alpha, TFPI protein levels
      declined significantly by 37.3% compared with controls (P < 0.001), and the mRNA
      levels of TFPI also decreased greatly (P < 0.001). A concentration of 30 nmol L(
      1) testosterone increased the secretion of TFPI compared with the TNF-alpha
      treated group. NF-kappaB DNA-binding activity was significantly suppressed by
      testosterone (P < 0.05). This suggests that physiological testosterone
      concentrations may exert their antithrombotic effects on TFPI expression during
      inflammation by downregulating NF-kappaB activity.

PMID- 19169267
TI  - Interstitial tissue-specific gene expression in mouse testis by intra-tunica
      albuguineal injection of recombinant baculovirus.
AB  - The purpose of this study is to establish a gene delivery system for interstitial
      tissue-specific protein expression in mice testes using modified recombinant
      baculovirus. Green fluorescent protein (GFP)-expressing recombinant baculovirus
      (GFP-baculovirus), in which the insect cell-specific polyhedron promoter was
      replaced by the cytomegalovirus (CMV)-IE promoter, was used to transfect
      testicular cells in vitro, and for intra-tunica albuguineal injection of the
      interstitial tissue of the testis. GFP expression was monitored in frozen testes
      sections by fluorescence microscopy. Expression of GFP in testicular tissues was
      also assessed by reverse transcription polymerase chain reaction (RT-PCR), and
      protein expression was assessed by Western blot. Testicular cells in vitro were
      infected efficiently by modified recombinant GFP-baculovirus. Intra-tunica
      albuguineal injection of GFP-baculovirus into the mouse testis resulted in a high
      level of GFP expression in the interstitial tissues. RT-PCR analysis clearly
      showed GFP gene expression in the testis, particularly interstitial tissues.
      Intra-tunica albuguineal injection of a modified baculovirus that encoded
      recombinant rat insulin-like growth factor binding protein (IGFBP)-5 resulted in
      an increase in IGFBP-5 in testis and semen. In conclusion, we have developed an
      efficient delivery system for gene expression in vivo in testicular cells,
      particularly cells of the interstitial tissue using intra-tunica albuguineal
      injection of a modified recombinant baculovirus. This method will be particularly
      relevant for application that requires gene delivery and protein expression in
      the testicular cells of the outer seminiferous tubule of the testis.

PMID- 19169268
TI  - Compound FLZ inhibits lipopolysaccharide-induced inflammatory effects via down
      regulation of the TAK-IKK and TAK-JNK/p38MAPK pathways in RAW264.7 macrophages.
AB  - AIM: The aim of this study was to investigate the effect of the squamosamide
      derivative FLZ (N-2-(4-hydroxy-phenyl)-ethyl-2-(2,5-dimethoxy-phenyl)-3-(3
      methoxy-4-hydroxy-phenyl)-acrylamide) on lipopolysaccharide (LPS)-induced
      inflammatory mediator production and the underlying mechanism in RAW264.7
      macrophages. METHODS: RAW264.7 cells were preincubated with non-toxic
      concentrations of compound FLZ (1, 5, and 10 micromol/L) for 30 min and then
      stimulated with 10 microg/L LPS. The production of nitric oxide (NO), the
      expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX
      2), and the activation of nuclear factor kappa-B (NF-kappaB) and mitogen
      activated protein kinase (MAPK) pathways were examined. RESULTS: FLZ
      significantly inhibited the LPS-induced production of NO, as well as the
      expression of iNOS and COX-2 at both the RNA and the protein levels in RAW264.7
      cells. The LPS-induced increase in the DNA binding activity of NF-kappaB and
      activator protein 1 (AP-1), the nuclear translocation of NF-kappaB p65, the
      degradation of the inhibitory kappaBalpha protein (IkappaBalpha) and the
      phosphorylation of IkappaBalpha, IkappaB kinase (IKK) alpha/beta, c-Jun NH(2)
      terminal kinase (JNK) and p38 MAPKs were all suppressed by FLZ. However, the
      phosphorylation of extracellular signal-regulated kinase (ERK) was not affected.
      Further study revealed that FLZ inhibited the phosphorylation of transforming
      growth factor-beta (TGF-beta)-activated kinase 1 (TAK1), which is an upstream
      signaling molecule required for IKKalpha/beta, JNK and p38 activation.
      CONCLUSION: FLZ inhibited the LPS-induced production of inflammatory mediators at
      least partly through the downregulation of the TAK-IKK and TAK-JNK/p38MAPK
      pathways.

PMID- 19169269
TI  - Proteomic analysis of the effect of iptakalim on human pulmonary arterial smooth
      muscle cell proliferation.
AB  - AIM: To investigate the anti-proliferative effect of iptakalim (Ipt), a newly
      selective K(ATP) channel opener, in endothelin-1 (ET-1)-induced human pulmonary
      arterial smooth muscle cells (PASMCs) using proteomic analysis. METHODS: Human
      PASMCs were incubated with ET-1 (10(-8) mol/L) and ET-1 (10(-8) mol/L) plus
      iptaklim (10(-5) mol/L) for 24 h. Analysis via 2-DE gel electrophoresis and MALDI
      TOF-MS was employed to display the different protein profiles of whole-cell
      protein from cultures of control, ET-1 treatment alone, and treatment with ET-1
      and iptaklim combined. Real time RT-PCR and Western blot analysis were used to
      confirm the proteomic analysis. RESULTS: When iptakalim inhibited the
      proliferative effect of ET-1 in human PASMCs by opening the K(ATP) channels, the
      expression of different groups of cellular proteins was changed, including
      cytoskeleton-associated proteins, plasma membrane proteins and receptors,
      chaperone proteins, ion transport-associated proteins, and glycolytic and
      metabolism-associated proteins. We found that iptakalim could inhibit the
      proliferation of human PASMCs partly by affecting the expression of Hsp60,
      vimentin, nucleoporin P54 (NUP54) and Bcl-X(L) by opening the K(ATP) channel.
      CONCLUSION: The data suggest that a wide range of signaling pathways may be
      involved in abolishing ET-1-induced proliferation of human PASMCs following
      iptakalim treatment.

PMID- 19169270
TI  - Discovery of potent beta-secretase (bace-1) inhibitors by the synthesis of
      isophthalamide-containing hybrids.
AB  - AIM: The aim of this study was to design and synthesize a series of high activity
      compounds against aspartyl protease beta-secretase (BACE-1) bearing
      hydroxyethylene (HE) framework. METHODS: First, we designed the small library
      based on our previous work and rational analysis. Subsequently, thirteen
      compounds were selected and synthesized using skilled solid phase synthetic
      methods to explore the relationship between structure and activity. We then used
      molecular modeling to explain the possible binding mode. RESULTS: Thirteen new
      compounds (6-18) have been designed, synthesized and bioassayed. Their structures
      were determined by nuclear magnetic resonance (NMR) spectra, low- and high
      resolution mass spectra and optical rotation. Most compounds have shown moderate
      to excellent activities, and compound 10, which contains fewer amino acids and
      amide bonds than GRL-7234, was about 5-fold more potent than the control compound
      4 discovered by Merck. The molecular modeling results have indicated the possible
      binding mode and explained the difference between compounds 10 and 16, providing
      direction for further study. CONCLUSION: This study yielded several high activity
      compounds bearing fewer amino acids and amide bonds than previous compounds,
      providing insight into the further development of potent BACE-1 inhibitors for
      the treatment of Alzheimer's disease.

PMID- 19169271
TI  - Suppression of complete Freund's adjuvant-induced adjuvant arthritis by
      cobratoxin.
AB  - AIM: Cobratoxin (CTX), the long-chain alpha-neurotoxin from Thailand cobra venom,
      has been demonstrated to have analgesic action in rodent pain models. The present
      study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on
      adjuvant arthritis (AA) in rats. METHODS: Arthritis was induced by injection of
      complete Freund's adjuvant (CFA) in rats. Paw swelling and hyperalgesia of AA
      rats were measured at various times after CFA administration. Tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-2 (IL-2) and
      interleukin-10 (IL-10) levels in serum were determined with ELISA.
      Histopathological changes in synoviocytes were examined under a microscope.
      Involvement of the cholinergic system in the effects of CTX was examined by
      pretreatment of animals with the alpha(7) nicotinic receptor (alpha(7)-nAChR)
      antagonist methyllycaconitine (MLA). RESULTS: CFA induced marked paw swelling and
      reduced thresholds of mechanical and cold-induced paw withdrawal. The levels of
      TNF-alpha, IL-1 and IL-2 in the serum of AA rats were increased, whereas the
      level of IL-10 was decreased. Histopathological examination of synoviocytes
      showed pronounced inflammation and accumulation of collagen. The administration
      of CTX (17.0 microg/kg, ip) significantly reduced paw swelling and mechanical and
      thermal hyperalgesia. CTX also reduced the production of TNF-alpha, IL-1, and IL
      2 but increased the production of IL-10 and altered pathohistological changes.
      The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by
      MLA (3 mg/kg, sc). CONCLUSION: These results indicate that CTX has a beneficial
      effect on CFA-induced arthritis by modulating the production of inflammatory
      cytokines. alpha(7)-nAChR appears to mediate the anti-nociceptive and anti
      inflammatory actions of CTX.

PMID- 19169272
TI  - The protective effect of the RAS inhibitor on diabetic patients with nephropathy
      in the context of VEGF suppression.
AB  - AIM: The aim of the present study was to explore whether renin angiotensin system
      (RAS) inhibitor can reduce the production of vascular endothelium growth factor
      (VEGF). Further, we sought to elucidate the correlation between VEGF level and
      certain clinical parameters, such as albumin excretion rate (AER), before and
      after treatment with angiotensin type 1 receptor blocker. METHODS: We recruited
      166 type 2 diabetic patients at various stages of diabetic nephropathy (DN) and
      46 healthy control subjects for a cross-sectional study. We recruited another 42
      hypertensive type 2 diabetic patients with microalbuminuria for a longitudinal
      study involving a 6-month irbesartan treatment protocol. Urinary VEGF (uVEGF)
      levels were determined using ELISA. RESULTS: In the cross-sectional study,
      hypertensive type 2 diabetic patients who received RAS inhibitor presented lower
      uVEGF levels than those who did not receive the RAS inhibitor. Statistical
      analysis indicated that uVEGF level was independently correlated with the AER. In
      the longitudinal study involving the 6-month irbesartan treatment, we
      demonstrated that uVEGF levels decreased significantly in patients who achieved a
      50% AER reduction (remission group, n=32). In contrast, uVEGF levels remained
      unchanged in patients who did not exhibit a 50% AER reduction (nonremission
      group, n=10). Furthermore, the change in uVEGF was significantly correlated with
      the change in AER (r=0.65, P<0.01) before and after 6 months of irbesartan
      treatment. This result held true even after we had adjusted for the decrease in
      average blood pressure. CONCLUSION: The protective effect of the RAS inhibitor in
      DN patients is associated with the suppression of VEGF. Accordingly, it may be
      possible to use uVEGF as a marker of DN progression. We suggest that uVEGF may be
      an important target for therapeutic intervention in the context of DN.

PMID- 19169273
TI  - Epidermal growth factor-dependent cyclooxygenase-2 induction in gliomas requires
      protein kinase C-delta.
AB  - Earlier, we showed that epidermal growth factor receptor (EGFR) signaling in
      human glioma cells increased cyclooxygenase-2 (COX-2) expression through p38
      mitogen-activated protein kinase (MAPK)-dependent activation of the Sp family of
      transcription factors. Further mechanistic details of EGFR-dependent induction of
      COX-2 expression in glioma cells remained elusive. Protein kinase Cs (PKCs)
      comprise a family of serine-threonine kinases that are major mediators of
      signaling from receptor tyrosine kinases. Here, we report that PKC-delta, a novel
      PKC isoform, plays a role in EGF-dependent COX-2 induction in human glioma cells.
      Pharmacological inhibition and genetic silencing (through siRNA or dominant
      negative expression) of PKC-delta confirm a role for this PKC isoform in EGF
      dependent COX-2 induction. Overexpression of a functional PKC-delta enhanced COX
      2 expression indicating that PKC-delta is not only necessary but also sufficient
      to regulate COX-2 levels. Inhibition of p38-MAPK pharmacologically or with siRNA
      further shows that p38-MAPK is required for activation of PKC-delta by EGF while
      inhibition of PKC-delta had no discernible effects on p38-MAPK activation.
      Finally, EGF stimulation promotes physical interactions between PKC-delta and Sp1
      resulting in phosphorylation and nuclear localization of this transcription
      factor. These data provide the first evidence that PKC-delta is a critical link
      between p38-MAPK and Sp1-dependent COX-2 expression in human glioma cells.

PMID- 19169274
TI  - Identification of (1H)-pyrroles as histone deacetylase inhibitors with
      antitumoral activity.
AB  - Histone deacetylases (HDACs) play a key role in the regulation of gene expression
      and chromatin structure, and drugs targeting these enzymes might have an
      important impact in the treatment of human cancer. Herein, we report the
      characterization of (1H)-pyrroles as a new subfamily of HDAC inhibitors obtained
      by computational modeling of class-I human HDACs. From a functional standpoint,
      (1H)-pyrroles are powerful inductors of acetylation of histones H3 and H4, and
      restore the expression of growth-inhibitory genes. From a cellular view, these
      compounds cause a marked decrease in the viability of cancer cells in vitro and
      in vivo, associated with a cell-cycle arrest at G2/M and an inhibition of
      angiogenesis. Thus, (1H)-pyrroles emerge as a novel group of HDAC inhibitors with
      promising antitumoral features.

PMID- 19169275
TI  - Regulation of microRNA expression by HMGA1 proteins.
AB  - The High Mobility Group proteins HMGA1 are nuclear architectural factors that
      play a critical role in a wide range of biological processes. Since recent
      studies have identified the microRNAs (miRNAs) as important regulators of gene
      expression, modulating critical cellular functions such as proliferation,
      apoptosis and differentiation, the aim of our work was to identify the miRNAs
      that are physiologically regulated by HMGA1 proteins. To this purpose, we have
      analysed the miRNA expression profile of mouse embryonic fibroblasts (MEFs)
      carrying two, one or no Hmga1 functional alleles using a microarray (miRNA
      microarray). By this approach, we found a miRNA expression profile that
      differentiates Hmga1-null MEFs from the wild-type ones. In particular, a
      significant decrease in miR-196a-2, miR-101b, miR-331 and miR-29a was detected in
      homozygous Hmga1-knockout MEFs in comparison with wild-type cells. Consistently,
      these miRNAs are downregulated in most of the analysed tissues of Hmga1-null mice
      in comparison with the wild-type mice. ChIP assay shows that HMGA1 is able to
      bind regions upstream of these miRNAs. Moreover, we identified the HMGA2 gene
      product as a putative target of miR-196a-2, suggesting that HMGA1 proteins are
      able to downregulate the expression of the other member of the HMGA family
      through the regulation of the miR-196a-2 expression. Finally, ATXN1 and STC1 gene
      products have been identified as targets of miR-101b. Therefore, it is reasonable
      to hypothesize that HMGA1 proteins are involved in several functions by
      regulating miRNA expression.

PMID- 19169276
TI  - Ha-Ras transformation of MCF10A cells leads to repression of Singleminded-2s
      through NOTCH and C/EBPbeta.
AB  - We have previously shown that Singleminded-2s (SIM2s), a member of the basic
      helix-loop-helix Per-Arnt-Sim (bHLH/PAS) family of transcription factors, is
      downregulated in breast cancer samples and has tumor suppressor activity.
      However, the mechanism by which SIM2s is repressed in breast cancer cells has not
      been determined. In this study, we show that transformation of MCF10A cells by
      Harvey-Ras (Ha-Ras) induces CCAAT/enhance binding protein beta (C/EBPbeta) and
      activates the NOTCH signaling pathway to block SIM2s gene expression. NOTCH
      mediated repression acts through a C-repeat binding factor 1 (CBF1)-independent
      mechanism, as introduction of CBF1 had no effect on SIM2s expression. Consistent
      with C/ebpbeta-dependent inhibition of SIM2s, C/ebpbeta(-/-) mouse mammary glands
      express high levels of SIM2s and reestablishment of C/ebpbeta isoforms decreased
      SIM2s mRNA levels in C/ebpbeta immortalized mammary epithelial cell lines. These
      studies illustrate a novel pathway of tumor suppressor gene silencing in Ha-Ras
      transformed breast epithelial cells and identify SIM2s as a target of C/EBPbeta
      and NOTCH signaling.

PMID- 19169277
TI  - Activation of the unliganded estrogen receptor by prolactin in breast cancer
      cells.
AB  - Both prolactin (PRL) and estrogen (E2) are involved in the pathogenesis and
      progression of mammary neoplasia, but the mechanisms by which these hormones
      interact to exert their effects in breast cancer cells are not well understood.
      We show here that PRL is able to activate the unliganded estrogen receptor (ER).
      In breast cancer cells, PRL activates a reporter plasmid containing estrogen
      response elements (EREs) and induces the ER target gene pS2. These actions are
      blocked by the antagonist ICI 182,780, showing that ER is required for the PRL
      mediated effect. Moreover, PRL leads to phosphorylation of ERalpha in serine-118
      (P-ERalpha), a modification related to the potentiation of ligand-independent
      transcriptional activation. In addition, PRL mimics the effect of E2 on target
      gene expression by inducing cyclical recruitment of ERalpha and P-ERalpha to ERE
      containing promoters, resulting in recruitment of co-activators and acetylation
      of histone H3. Finally, PRL induces expression of c-Myc and Cyclin D1 and leads
      to increased cell proliferation, which is specifically antagonized by ICI 182,780
      or ERalpha depletion. These results show that ligand-independent ERalpha
      activation appears to be an important component of the proliferative and
      transcriptional actions of PRL in breast cancer cells.

PMID- 19169278
TI  - Runx3 expression in gastrointestinal tract epithelium: resolving the controversy.
AB  - We reported earlier that RUNX3 is expressed in human and mouse gastrointestinal
      tract (GIT) epithelium and that it functions as a tumor suppressor in gastric and
      colorectal tissues. However, there have been conflicting reports describing the
      absence of Runx3 in GIT epithelial cells. A part of the controversy may be
      derived from the use of a specific antibody by other groups (referred to as G
      poly). Here, we show further evidence to support our earlier observations and
      provide a possible explanation for this apparent controversy. We generated
      multiple anti-RUNX3 monoclonal antibodies and found that RUNX3 antibodies
      recognizing the RUNX3 N-terminal region (residues 1-234) react with RUNX3 in
      gastric epithelial cells, whereas those recognizing the C-terminal region (beyond
      residue 234) did not. G-poly primarily recognizes the region beyond 234 and
      hence, is unable to detect Runx3 in this tissue.

PMID- 19169279
TI  - The p400/Tip60 ratio is critical for colorectal cancer cell proliferation through
      DNA damage response pathways.
AB  - The Tip60 histone acetyltransferase belongs to a multimolecular complex that
      contains many chromatin remodeling enzymes including the ATPase p400, a protein
      involved in nucleosomal incorporation of specific histone variants and that can
      directly or indirectly repress some Tip60-dependent pathways. Tip60 activity is
      critical for the cellular response to DNA damage and is affected during cancer
      progression. Here, we found that the ratio between Tip60 and p400 mRNAs is
      affected in most colorectal carcinoma. Strikingly, reversing the p400/Tip60
      imbalance by Tip60 overexpression or the use of siRNAs resulted in increased
      apoptosis and decreased proliferation of colon-cancer-derived cells, suggesting
      that this ratio defect is important for cancer progression. Furthermore, we
      demonstrate that the p400/Tip60 ratio controls the oncogene-induced DNA damage
      response, a known anticancer barrier. Finally, we found that it is also critical
      for the response to 5-fluorouracil, a first-line treatment against colon cancer.
      Together, our data indicate that the p400/Tip60 ratio is critical for colon
      cancer cells proliferation and response to therapeutic drugs through the control
      of stress-response pathways.

PMID- 19169280
TI  - Chk1 deficiency in the mouse small intestine results in p53-independent crypt
      death and subsequent intestinal compensation.
AB  - Chk1 is a serine/threonine protein kinase that is activated by a wide range of
      DNA-damaging agents to slow the cell cycle during S phase and G2/M. Abrogation of
      these cell-cycle checkpoints using Chk1 inhibitors results in hypersensitivity to
      DNA-damaging agents in vitro and may provide a potential therapeutic tool to
      sensitize tumour cells in vivo. We have generated a Cre-Lox-based mouse model in
      which Chkl can be inducibly deleted from somatic epithelial cells in the adult
      mouse small intestine and liver. Loss of Chk1 in the liver is tolerated with no
      apparent phenotype. In contrast, the loss of Chk1 within the small intestine
      results in immediate DNA damage and high levels of p53-independent apoptosis
      leading to crypt death. However, the intestine is able to compensate for this
      death by undergoing complete re-population with Chk1-proficient cells. These data
      therefore show that Chk1 deficiency is cell lethal, but the intestine can
      tolerate such lethality at the organ level.

PMID- 19169281
TI  - The membrane-anchored metalloproteinase regulator RECK stabilizes focal adhesions
      and anterior-posterior polarity in fibroblasts.
AB  - Accumulating evidence indicates that Reversion-inducing cysteine-rich protein
      with Kazal motifs (RECK), a membrane-anchored matrix metalloproteinase regulator,
      plays crucial roles in mammalian development and tumor suppression. Its
      mechanisms of action at the single cell level, however, remain largely unknown.
      In mouse fibroblasts, RECK is abundant around the perinuclear region, membrane
      ruffles and cell surface. Cells lacking Reck show decreased spreading, ambiguous
      anterior-posterior (AP) polarity, and increased speed and decreased directional
      persistence in migration; these characteristics are also found in transformed
      fibroblasts and fibrosarcoma cells with low RECK expression. RECK-deficient cells
      fail to form discrete focal adhesions, have increased levels of GTP-bound Rac1
      and Cdc42, and a marked decrease in the level of detyrosinated tubulin, a
      hallmark of stabilized microtubules. RECK-deficient cells also show elevated
      gelatinolytic activity and decreased fibronectin fibrils. The phenotype of RECK
      deficient cells is largely suppressed when the cells are plated on fibronectin
      coated substrates. These findings suggest that RECK regulates pericellular
      extracellular matrix degradation, thereby allowing the cells to form proper cell
      substrate adhesions and to maintain AP polarity during migration; this mechanism
      is compromised in malignant cells.

PMID- 19169282
TI  - The Tcl1 oncogene defines secondary hair germ cells differentiation at catagen
      telogen transition and affects stem-cell marker CD34 expression.
AB  - Overexpression of the TCL1 gene family plays a role in the onset of T-cell
      leukemias in mice and in humans. The Tcl1 gene is tightly regulated during early
      embryogenesis in which it participates in embryonic stem (ES)-cells proliferation
      and during lymphoid differentiation. Here, we provide evidences that Tcl1 is also
      important in mouse hair follicle (HF) and skin homeostasis. We found that Tcl1(-/
      ) adult mice exhibit hair loss, leading to alopecia with extensive skin lesions.
      By analysing Tcl1 expression in the wild-type (wt) skin through different stages
      of hair differentiation, we observe high levels in the secondary hair germ (HG)
      cells and hair bulges, during early anagen and catagen-telogen transition phases.
      The loss of Tcl1 does not result in apparent skin morphological defects during
      embryonic development and at birth, but its absence causes a reduction of
      proliferation in anagen HFs. Importantly, we show the that absence of Tcl1
      induces a significant loss of the stem-cell marker CD34 (but not alpha6-integrin)
      expression in the bulge cells, which is necessary to maintain stem-cell
      characteristics. Therefore, our findings indicate that Tcl1 gene(s) might have
      important roles in hair formation, by its involvement in cycling and self-renewal
      of transient amplifying (TA) and stem-cell (SC) populations.

PMID- 19169283
TI  - The EBMT activity survey 2007 with focus on allogeneic HSCT for AML and novel
      cellular therapies.
AB  - The 2007 report describes the current status of HSCT activity in Europe,
      highlights the increasing role of allogeneic HSCT in treatment of AML and gives
      the first quantitative information on novel cellular therapies. In 2007, there
      were 25 563 first HSCTs, 10 072 allogeneic (39%), 15 491 autologous (61%) and
      3606 additional transplants reported from 613 centers in 42 countries. The main
      indications were leukemias (8061 (32%; 89% allogeneic)); lymphomas (14 627 (57%;
      89% autologous)), solid tumors (1488 (6%; 96% autologous)) and nonmalignant
      disorders (1302 (5%; 91% allogeneic)). Peripheral blood was the main source of
      stem cells for autologous HSCT (98%) and the predominant source for allogeneic
      HSCT (71%). Among allogeneic HSCTs, the number of unrelated donor grafts equaled
      the number of HLA-identical sibling donor grafts for the first time (47% each).
      AML was the most frequent indication for allogeneic HSCT (32% of all allogeneic
      HSCTs), with an increase of 247 (8%). Information on novel cellular therapies was
      collected for the first time; there were 212 mesenchymal SCTs and 212 HSCTs for
      nonhematopoietic use. The indications for the latter were cardiovascular
      disorders (97; 46%), neurological disorders (94; 44%) and tissue repair (21;
      10%). These data illustrate the expanding role of cellular therapies.

PMID- 19169284
TI  - KIR genes and KIR ligands affect occurrence of acute GVHD after unrelated, 12/12
      HLA matched, hematopoietic stem cell transplantation.
AB  - Interactions of polymorphic killer Ig-like receptor (KIR) receptors with KIR
      ligands have been shown to modify the outcome of hematopoietic SCT (HSCT). The
      association of these genetic factors with different transplantation endpoints,
      however, varies substantially, depending on clinical and study setup variables.
      We aimed to assess whether KIR ligands, KIR genes and KIR haplotypes are
      associated with HSCT outcome of 124 patients with various hematological
      malignancies, transplanted with 12/12 HLA matched grafts from unrelated donors.
      For this purpose, patient and donor KIR gene and KIR ligand polymorphisms were
      determined and correlated with clinical data in simple and multiple models. We
      found that a missing HLA-C2 ligand for donor inhibitory KIR2DL1 was significantly
      associated with an increased risk of acute GVHD (aGVHD) (II-IV) (hazard ratio
      (HR)=2.23, 95% confidence interval (95% CI): 1.21-4.10, P=0.010), as were the AA
      KIR haplotypes in patients and donors in HLA-C1CX (HR=2.37, 95% CI: 1.16-4.84,
      P=0.018) and in HLA-Bw4(-) (HR=3.20, 95% CI: 1.35-7.60, P=0.008) patients. On the
      contrary, transplantation of HLA-C1C2 patients with KIR2DS2 positive grafts were
      associated with a decreased risk of aGVHD (II-IV) (HR=0.24, 95% CI: 0.07-0.85,
      P=0.027). Thus, our single center study provides evidence for the modification of
      aGVHD risk by KIRs and their ligands.

PMID- 19169286
TI  - Diphyllobothriasis, a rare cause of profuse diarrhea following autologous
      transplantation.

PMID- 19169285
TI  - Multiple pretibial cutaneous relapses of acute myeloblastic leukemia after
      allogeneic BMT.

PMID- 19169287
TI  - Autologous transplantation for relapsed non-Hodgkin's lymphoma using intravenous
      busulfan and cyclophosphamide as conditioning regimen: a single center
      experience.
AB  - High-dose chemotherapy with autologous SCT has become standard of care for
      patients with relapsed aggressive non-Hodgkin's lymphoma (NHL). To improve safety
      and efficacy of this treatment, new conditioning regimens are being developed. We
      retrospectively reviewed clinical data of patients with relapsed NHL treated at
      our institution with i.v. BU and CY (BU/CY) as conditioning regimen for
      autologous SCT between January 2000 and April 2005. We identified 43 patients (24
      men, 19 women, median age 50) with diffuse large B-cell lymphoma (n=28),
      follicular lymphoma (n=8), mantle cell lymphoma (n=4) and peripheral T-cell
      lymphoma (n=3). Following salvage chemotherapy, there were 26 complete responses,
      13 partial responses and 4 stable diseases. Median time to neutrophil and
      platelet recovery was 11 and 13.5 days, respectively. Treatment-related
      toxicities included nausea/vomiting, diarrhea and mucositis. The 100-day
      mortality was 9%: sepsis (n=1), pneumonia (n=1) and hepatic veno-occlusive
      disease (n=2). Twenty-one patients were followed until death and twenty-one
      surviving patients were followed for a median of 29 months (range 0.4-76). Three
      year estimates of event-free survival, progression-free survival and overall
      survival were 35, 39 and 43%, respectively. We conclude that i.v. BU/CY is a safe
      and effective conditioning regimen for autologous SCT in relapsed NHL.

PMID- 19169288
TI  - Efficient mobilization of PBSC with vinorelbine/G-CSF in patients with malignant
      lymphoma.
AB  - High-dose chemotherapy (HDT) and hematopoietic SCT are effective in patients with
      relapsing or refractory malignant lymphoma. Collection of sufficient numbers of
      stem cells is a prerequisite for such a therapy. In a pilot trial, we evaluated
      the feasibility of stem cell mobilization with vinorelbine/G-CSF in patients with
      lymphoma, a regimen allowing precise timing and harvesting of sufficient stem
      cells in myeloma patients. Forty-five patients with lymphoma received vinorelbine
      35 mg/m(2) i.v. on day 1 and G-CSF 10 microg/kg/day s.c., divided in two daily
      doses from day 4 until collection. Stem cell collection was successfully
      performed in 43 patients (96%) with a median of 3.6 x 10(6) CD34(+) cells/kg
      (range: 1.4-16) in the collected product. In 28 patients (62%), the first stem
      cell apheresis was performed on day 8, and for 28 patients a sufficient stem cell
      yield was reached with one apheresis only. All 43 patients underwent high-dose
      chemotherapy with BEAM and auto-SCT with hematological recovery on time and
      without unexpected toxicity. In conclusion, vinorelbine/G-CSF allows accurate
      timing and safe harvesting of sufficient stem cells in patients with malignant
      lymphoma.

PMID- 19169289
TI  - Pegfilgrastim for peripheral CD34+ mobilization in patients with solid tumours.
AB  - The efficacy of pegfilgrastim+/-chemotherapy for mobilizing stem cells in
      patients with solid tumours was assessed. In cycle 0, a 14-day prechemotherapy
      cycle, patients (N=61) were randomized open-label to single doses of
      pegfilgrastim (6, 12 or 18 mg) on day 1, or daily filgrastim (10 microg/kg) for <
      or =7 days. Mean peak peripheral CD34+ cell counts increased with pegfilgrastim
      dose, but were significantly higher than filgrastim only at the 18 mg dose (10.17
      vs 4.96 x 10(4)/ml; P=0.014). In the clinically relevant period of days 3-7, both
      12 and 18 mg pegfilgrastim doses produced significantly higher peak CD34+ counts
      (8.18 and 9.96 vs 4.51 x 10(4)/ml for filgrastim; P=0.034 and 0.006). In cycle 1,
      patients received carboplatin/paclitaxel on day 1, followed from day 2 by
      pegfilgrastim 6-18 mg or daily filgrastim (5 microg/kg/day for < or =14 days) as
      per randomization in cycle 0. There were no significant differences in mean peak
      CD34+ count between pegfilgrastim and filgrastim, but there was an advantage for
      pegfilgrastim 18 mg in the relevant period of days 7-12 (3.14 vs 1.19 x 10(4)/ml;
      P=0.043). A single pegfilgrastim dose (> or =6 mg) could be substituted for daily
      filgrastim in cytokine-only peripheral CD34+ cell mobilization.

PMID- 19169290
TI  - [Ocular manifestations of systemic diseases].
AB  - A great number of systemic diseases can exhibit ocular manifestations during
      their evolution. These ocular alterations may cause symptoms by themselves, but
      can also be useful in diagnosing or monitoring the evolution of the systemic
      condition. The main characteristics of several systemic diseases exhibiting some
      kind of ocular sign are highlighted. These diseases will be described in detail
      in this issue.

PMID- 19169292
TI  - [Diabetic retinopathy].
AB  - Diabetes mellitus is a metabolic pathology whose evolution affects different
      organs, amongst them the eye. Diabetic microangiopathy affects the retina in an
      early and specific way. The appearance of retinopathy is directly related to the
      time of evolution of the disease and metabolic control. Diabetic microangiopathy
      in the retina shows specific alterations such as micro-aneurysms, soft or hard
      exudates, intra-retinal micro-haemorrhages, beaded veins and intraretinal
      microvascular anomalies. These alterations in the retinal microcirculation cause
      two physiopathological phenomena: capillary closure with the resulting ischaemia
      or extravasation of intravascular content to the stroma causing edema. In this
      chapter we set out the classification and treatments of diabetic retinopathy,
      excluding macular edema, according to the different multicentric studies present
      in the current bibliography.

PMID- 19169291
TI  - [Ophthalmological manifestations of arterial hypertension].
AB  - Systemic Arterial hypertension (AHT) is one of the most frequent diseases in the
      industrialised countries, with an incidence reaching 30%, a figure that is rising
      due to the greater life expectancy of the population. This rise in arterial
      tension causes, or accelerates, changes in the vascular wall of the target organs
      such as the kidney, brain, heart and eye. At the ocular level, AHT produces
      lesions in the retina, the choroids and optic nerve head; this can include a wide
      range of lesions, from slight vascular narrowing to severe visual loss due to
      ischaemic optical neuropathy. The primary response of the retinal arteries to
      systemic arterial hypertension is vascular narrowing and the manifestations that
      appear at the back of the eye in hypertensive retinopathy are diffuse or focal
      vasoconstriction, extravasation due to increased vascular permeability and
      arteriosclerosis with swelling of the wall of the vessels. These three entities
      are responsible for the appearance of different lesions that characterise the
      stages of the retinal disease, which are: arteriovenous crossings, hard and
      cotton-like exudates, thrombosis, embolisms, haemorrhages in the retinal
      parenchyma, vitreous detachment from the retina, papilla edema and ischaemic
      optical neuropathy in the more severe cases, such as in case malign arterial
      hypertension.

PMID- 19169293
TI  - [Diabetic macular edema].
AB  - Diabetic macular edema is the principal cause of visual loss in patients with
      diabetes mellitus. Its complexity, together with the appearance of new methods of
      diagnosis and new alternatives for treatment, mean that the approach to this
      disease is an important challenge for ophthalmologists. This article describes
      its pathophysiology, clinical manifestations, classification, diagnosis and
      treatment, with special emphasis on the new diagnostic methods and on the
      different therapeutic options.

PMID- 19169294
TI  - [Clinical manifestations of thyroid ophthalmopathy].
AB  - Ophthalmopathy is a common manifestation of autoimmune thyroid disease.
      Periorbital swelling, eyelid lag, exophthalmos, and impaired vision may occur.
      From 25% to 50% of patients with Graves' hyperthyroidism will have some features
      of ophthalmopathy. All of the clinically significant eye symptoms and findings
      among patients with Graves' ophthalmopathy can be traced to one of two phenomena:
      swelling in the retrobulbar space due to deposition of glycosaminoglycans (GAG)
      or restriction of extraocular muscle motion, which is attributed to initial
      swelling and later fibrosis. Patients with Graves' eye disease typically complain
      of ocular or periocular pain, lacrimation, photophobia, blurred vision, diplopia,
      or impaired perception of colour. On examination, they exhibit orbital
      congestion, proptosis, optic neuropathy, restricted gaze, divergent visual axis,
      corneal exposure, lid retraction, and periorbital edema. This paper describes the
      main clinical features of Graves' ophthalmopathy, in order to establish
      measurable and reproducible classifications that can be used in the surgery
      setting to record changes and to guide and assess therapy. Finally, we recommend
      the use of objective measurements for proptosis, extraocular movements, corneal
      alterations, and the optic nerve, using the clinical activity scale or a recorded
      change in objective measurements to document disease activity, and lastly,
      documenting the patients' perception of their disease status.

PMID- 19169295
TI  - [Retinal manifestations of infectious diseases].
AB  - The retina and the choroids are richly vascularised structures and can therefore
      be colonised by germs via the haematogenous route in the course of a systemic
      infectious disease. The germs responsible for this type of infection can be
      fungi, viruses, bacteria and parasites. Ocular candidiasis is outstanding amongst
      these colonisations because of its frequency; it can manifest itself as an
      endophthalmitis with a slow and hidden course. The so-called ocular
      histoplasmosis syndrome, although it is infrequent in our setting, is an
      important cause of choroidal neovascularisation. The viruses that most frequently
      affect the retina are of the herpes type and can produce devastating symptoms in
      immunoincompetent patients, named acute retinal necrosis syndrome. Retinitis due
      to cytomegalovirus is more frequent in immunodepressed patients, as in the case
      of AIDS, but it must also be contemplated in patients with lymphoma and
      immunomodulatory treatment. The most frequent bacterial diseases that affect the
      retina are syphilis and tuberculosis. Disease due to cat scratches, caused by a
      borrelia, can produce a neuroretinitis. Toxoplasmosis is the most common of the
      infectious diseases caused by a parasite and gives rise to chorioretinitis.
      Toxocariasis, also caused by a parasite, is second in importance, giving rise to
      choroidal granulomas and retinal tractions.

PMID- 19169296
TI  - [AIDS and ophthalmology: a contemporary view].
AB  - The appearance of the Acquired Immune Deficiency Syndrome (AIDS) meant a
      revolution in medicine, which has also affected Ophthalmology: the routine
      presence of ophthalmological pathologies which until then had been exceptional,
      such as retinitis due to cytomegalovirus (CMV), and the appearance of other new
      pathologies such as progressive outer retinal necrosis (PORN). The generalised
      use of high activity antiretroviral therapy (HAART) in the second half of the
      1990s represented a turning point, since when the immunological improvement of
      patients with Human Immunodeficiency Virus (HIV) resulted in a fall in the cases
      with ophthalmological pathology associated to immunodepression (HIV retinopathy,
      retinitis due to CMV, PORN...), and the spontaneous improvement of symptoms which
      until then had had a torpid evolution (Kaposi's ocular sarcoma, Palpebral
      Molluscum...). On the other hand, the continuous increase in the prevalence of
      syphilis in these patients means an increase in the number of cases of ocular
      syphilis unassociated with immunodepression. New ophthalmological alterations
      also appear that are related to HAART: uveitis due to immune recovery in patients
      with CMV retinitis in complete remission and the enophthalmos due to the atrophy
      of orbital fat in the context of lipodystrophy, associated with antiretrovirals.
      At present preventive ophthalmological checks must be carried out on patients
      with severe immunodepression until a count of lymphocytes above 100 cells/microl
      is confirmed. If they also show HIV retinopathy, a monthly check up is advisable
      until immune recovery, given the greater risk of infection by CMV.

PMID- 19169297
TI  - [Articular diseases and uveitis].
AB  - Ocular inflammation is a common clinical manifestation related to several
      autoimmune systemic disorders, specially spondyloarthropaties. In this group,
      there are different clinical diseases that are related to special uveitic
      patterns. Several discriminative patterns have been defined that closely link
      uveitis with certain systemic or ophthalmic diseases. Unilateral recurrent
      anterior acute uveitis is the most frequent form of uveitis related to
      spondyloarthropaties, and is sometimes the initial manifestation of an
      undiagnosed spondyloarthropaty. The collaboration of ophthalmologists,
      rheumatologists and internal medicine specialists is very important for the
      correct management and treatment of these patients.

PMID- 19169298
TI  - [Non-infectious systemic diseases and uveitis].
AB  - Uveitis can be defined as any inflammation affecting the uveal tract, although in
      clinical practice this term includes any intraocular inflammatory event. The
      etiology of this inflammation can be related to an endogenous mechanism in the
      clinical course of a systemic disease (sarcoidosis, Behcet's disease, multiple
      sclerosis, Vogt-Koyanagi-Harada disease, etc.), or an isolated ocular entity.
      Sometimes, ocular inflammation is the initial manifestation of an undiagnosed
      systemic disease. On the other hand, ocular involvement could be the main cause
      of morbidity of the disease, and early diagnosis and treatment is an important
      issue in order to avoid irreversible ocular damage. In this article, the authors
      review some relevant clinical, diagnostic and therapeutic topics related to the
      most common non-infectious systemic diseases associated with uveitis.

PMID- 19169299
TI  - [Ophthalmological manifestations of cerebrovascular disease].
AB  - Transient or persistent loss of vision in one eye is a common and distinctive
      manifestation of occlusive vascular disease. Occasionally, both eyes are involved
      together or sequentially, with temporary or even permanent blindness. The
      internal carotid arteries supply blood to the organ of vision; therefore
      pathologies of those arteries caused by arteriosclerosis may have a direct
      influence on its functioning. The most common syndromes are temporary (amaurosis
      fugax) or constant reduction of visual acuity. In fundus examination central
      retinal artery occlusion and branch retinal artery occlusion are the most common
      diagnosis, while retinal vein occlusion, anterior ischemic optic neuropathy,
      ocular ischemic syndrome are less common. There are many clinical ophtlamological
      manifestations due to vascular brain damage. Proper recognition and diagnosis of
      the disease may protect the patient against serious life-threatening
      complications such as stroke.

PMID- 19169300
TI  - [Choroidal metastases].
AB  - Uveal metastases are the most frequent malign intraocular tumour, of which more
      than 80% are localized in the choroids. This, together with the progressive
      increase in its incidence, makes its study and review necessary for a correct
      diagnosis and treatment in current clinical practice. Etiology varies according
      to the sex of the patient: lung carcinoma metastasises most frequently in men and
      breast carcinoma in women. These tend to multifocality and are generally
      localized in the posterior pole. Fifty percent of cases follow an asymptomatic
      development, but they can cause loss of vision, scotomas, metamorphopsias and
      photopsias. Charactersitic ophthamoscopic examination shows a placoid, homogenous
      choroidal lesion with a creamy appearance. The differential diagnosis must
      consider the amelanotic nevus, choroidal amelanotic melanoma, choroidal
      haemangioma, rear scleritis, choroidal osteoma, chorioretinitis, Harada's
      disease, rhegmatogenous retina detachment, uveal effusion syndrome, and serous
      central chorioretinopathy. An exhaustive history and complete ophthalmological
      examination are essential to the diagnosis, to which fluorescein angiography,
      ocular echography, fine needle puncture aspiration (FNPA), computerized
      tomography and magnetic resonance can be added as complementary tests. Treatment
      of these tumours is usually the systemic treatment of the primary tumour; the
      possibilities of local treatment are observation, external radiotherapy,
      transpupillary thermotherapy and enucleation.

PMID- 19169301
TI  - [Orbital metastases of breast cancer].
AB  - Orbital metastases are a defined subgroup within ocular affection secondary to
      the distant spread of breast cancer. We review the published experience on the
      incidence of orbit extension from this type of tumour, with reference made to our
      experience as medical oncologists, together with the most common clinical
      features and the relevant aspects for imaging and histopathological diagnoses.
      The therapy for orbital metastases from breast cancer is included within the
      systemic therapy required by the distant spread of the disease, with some
      clinical benefits obtained from hormone therapy, chemotherapy and monoclonal
      antibodies. Palliative radiation and surgery may also play an important role in
      providing care to these patients. Although there are some published cases with
      long-term survival, the prognosis for these patients is poor, and new advances in
      knowledge and therapy are needed for this complication due to breast cancer.

PMID- 19169302
TI  - [Ocular toxicity induced by medication].
AB  - This paper analyses ocular toxicity induced by four groups of systemic medicines:
      tamoxifen, chloroquine and derivatives, anticholinergics and tamsulosin. Our main
      aim is to provide some practical rules that will be of use in the everyday
      management of patients receiving these treatments, rather than to examine the
      mechanisms by which each of these medicines act.

PMID- 19169303
TI  - [Corneal manifestations in systemic diseases].
AB  - Systemic diseases affecting the cornea have a wide range of manifestations. The
      detailed study of all pathologies that cause corneal alteration is
      unapproachable, so we have centered our interest in the most prevalent or
      characteristic of them. In this paper we have divided these pathologies in
      sections to facilitate their study. Pulmonar and conective tissue (like colagen,
      rheumatologic and idiopathic inflamatory diseases), dermatologic, cardiovascular,
      hematologic, digestive and hepatopancreatic diseases with corneal alteration are
      described. Endocrine and metabolic diseases, malnutrition and carential states
      are also studied, as well as some otorhinolaryngologic and genetic diseases that
      affect the cornea. Finally, a brief report of ocular toxicity induced by drugs is
      referred.

PMID- 19169305
TI  - Polymerase chain reaction or probable contaminated reagin?

PMID- 19169306
TI  - The future of cornea supply and demand.

PMID- 19169309
TI  - Applications of the polymerase chain reaction in clinical ophthalmology.
AB  - Molecular biology has become a valuable component in many areas of medicine,
      including ophthalmology. Polymerase chain reaction (PCR) is the most widely used
      tool. It has proven to be a powerful technique in diagnosis and quantification of
      microorganisms and antibiotic resistance screening. For a growing number of
      ophthalmic conditions PCR testing can be conducted. It is therefore important
      that clinicians be knowledgeable about the indications, strengths, and
      limitations of the technique. The purpose of this review is to explore the
      current role of PCR in the diagnosis and management of eye disease.

PMID- 19169310
TI  - Efficacy of Routine Notification and Request on reducing corneal transplantation
      wait times in Canada.
AB  - OBJECTIVE: To determine whether the implementation of Routine Notification and
      Request (RNR) has been effective in increasing the amount of donor corneal tissue
      available and reducing wait times for corneal transplant (CT) surgeries. DESIGN:
      Survey of the CT surgeons and eye banks in Canada. PARTICIPANTS: CT surgeons and
      representatives of the 10 eye banks in Canada. METHODS: Voluntary, anonymous
      questionnaires were distributed between May 1 and September 30, 2006. RESULTS:
      Following the implementation of RNR, 3 eye banks had an increase in the amount of
      corneal tissue available: Manitoba, 81% (from 42 tissues in 2004 to 76 tissues in
      2006); Ontario, 25% (from 1304 tissues in 2005 to 1626 tissues in 2006); New
      Brunswick, 129% (from 86 tissues in 2005 to 197 tissues in 2006). British
      Columbia, where RNR was implemented in 1999, had a 6% increase (from 766 in 2005
      to 812 in 2006). There has been a significant decrease in wait times from the
      time of diagnosis by CT surgeons to the time of surgery in British Columbia (from
      48+/-18 weeks in 2004 to 39+/-20 weeks in 2006), Manitoba (from 82+/-56 weeks in
      2004 to 32+/-23 weeks in 2006), Ontario (from 82+/-56 weeks in 2004 to 31+/-34
      weeks in 2006), and Nova Scotia (from 44+/-12 weeks in 2004 to 32+/-28 weeks in
      2006). CONCLUSIONS: RNR has been effective in increasing corneal tissue
      availability and decreasing wait times in provinces where it has been
      implemented. We recommend similar legislative changes to be considered in those
      provinces where corneal tissue shortage is delaying the availability of CT
      surgery.

PMID- 19169311
TI  - Cost of corneal transplantation for the Quebec health care system.
AB  - OBJECTIVE: Although corneal graft is a common, long-standing procedure, little is
      known about its economic impact. The purpose of this study was to estimate
      resource use and costs associated with corneal transplantation according to a
      public third-party perspective. DESIGN: Retrospective study using claim data from
      the Regie de l'assurance maladie du Quebec (RAMQ). PARTICIPANTS: A total of 610
      subjects were included in the study. Mean age was 54.8 (SD 20.4) years. METHODS:
      The RAMQ provided medical and pharmaceutical data for a random sample of 75% of
      the patients who underwent a corneal graft procedure between June 1, 1999, and
      May 31, 2002. Resource usage data, defined as medical interventions, physician
      visits, and medication, were collected for a 3-year postoperative follow-up
      period. Hospital costs associated with corneal graft were obtained from the
      University of Montreal Hospital Centre costing system. RESULTS: The average costs
      per patient for graft and anesthesia were $501 (SD $75) and $115 (SD $124),
      respectively. The mean cost per patient for physician visits was $276 (SD $146).
      The mean number of physician visits per patient during the follow-up was 14.9 (SD
      9.1). The cost per patient for medication was $337 (SD $1075). The average total
      cost per patient was $1229 (SD $1125). Costs incurred by the hospital represented
      a total of $1942. CONCLUSIONS: The overall cost of corneal graft, including a 3
      year follow-up, was estimated at $3171 ($1229 RAMQ, $1942 hospital). The majority
      of these costs occurred at the time of the procedure.

PMID- 19169312
TI  - Correctable visual impairment and its impact on quality of life in a marginalized
      Canadian neighbourhood.
AB  - OBJECTIVE: To study the impact of visual impairment due to either underlying
      ocular pathology or easily correctable refractive error on vision-related
      functioning and quality of life (QOL) in Vancouver's downtown eastside (VDES).
      DESIGN: Cross-sectional study. PARTICIPANTS: Two hundred consecutive patients
      seeking general medical care at the Vancouver Native Health Society (VNHS)
      medical clinic were included. METHODS: An ocular examination was performed and a
      standardized history and QOL information were obtained for each participant.
      Effective visual impairment was classified based on patients' current refractive
      means. Pathological visual impairment was classified based on patients' best
      corrected visual acuity (VA). Vision-related functioning was quantified using the
      Daily Tasks Dependent on Vision (DTDV) questionnaire. Health-related QOL was
      assessed using the 12-Item Short Form Health Survey (SF-12). RESULTS: Two hundred
      patients participated; they suffered, on average, 6.2 comorbid conditions. Sixty
      two patients (31%) were effectively visually impaired and, of these, 14 patients
      (7%) were effectively blind. Ten patients (5%) had pathological eye disease to
      explain their visual impairment. The remaining 52 visually impaired patients
      (26%) had VA that normalized with correction. Difficulty with the tasks described
      in the DTDV questions was significantly correlated with effective visual
      impairment. Patients with effective visual impairment had lower Physical
      Composite Scores on the SF-12 in multivariate analyses. CONCLUSIONS: We have
      demonstrated a very high rate of visual impairment in a low socioeconomic
      population that is associated with decreased vision-dependent functioning and
      decreased overall physical health status. Public health efforts need to be
      directed toward improving easily correctable refractive error.

PMID- 19169313
TI  - An examination of the relationship between low vision and Charles Bonnet
      syndrome.
AB  - OBJECTIVE: In recent years, the Low Vision Clinic (LVC) appeared to have a large
      percentage of patients admitting to phantom vision (Charles Bonnet syndrome
      [CBS]). The objective of this study was to learn more about CBS from an
      ophthalmological perspective, as research has been conducted primarily by other
      specialists. DESIGN: Large-scale prospective study using a cohort of low-vision
      and normal-vision subjects. PARTICIPANTS: Two hundred fifty-eight low-vision and
      251 control subjects (with little or no vision loss) were enrolled. METHODS: A
      comparison of visual acuity, ophthalmic conditions, eye treatments, medications,
      mental state, general health, socialization, etc., was undertaken, and other
      factors influencing the hallucinations were recorded. RESULTS: CBS was present in
      34% of LVC subjects and in <2% of the general population with little or no vision
      loss. Many subjects had unformed hallucinations; bright lights or spot-like
      images should not be overlooked because they could be determined to be
      hallucinations upon further questioning of the patient. CBS occurred in subjects
      with visual acuity from 20/40 to 20/1600; subjects were twice as likely to have
      CBS if their visual acuity was between 20/301 and 20/800. The prevalence of CBS
      did not differ significantly by cause of visual problem. Thirty-four percent of
      people were distressed about their initial hallucination; many did not consult a
      doctor for an explanation, and if they did, many did not receive an adequate
      explanation. CONCLUSIONS: This large-scale study shows that CBS is connected with
      a low vision level; thus, patients should be told about the common possibility of
      hallucinations.

PMID- 19169314
TI  - Giant cell arteritis in Alaska Natives.
AB  - OBJECTIVE: To investigate the incidence of biopsy-proven giant cell arteritis in
      the Native population of Alaska. DESIGN: Retrospective review of medical
      diagnostic and Current Procedural Terminology (CPT) codes. PARTICIPANTS: 110,000
      Alaska Native patients. METHODS: We conducted a retrospective review of medical
      diagnostic codes for temporal arteritis, giant cell arteritis, and anterior
      ischemic optic neuropathy in the medical records of 110,000 Alaska Native
      patients seen between 1983 and 2003. We examined this same database in search of
      the CPT code for the temporal artery biopsy procedure. We also re-examined all
      temporal artery biopsy specimens that had been reported as positive. RESULTS: We
      identified 122 patients whose diagnostic codes matched those of giant cell
      arteritis, temporal arteritis, or anterior ischemic optic neuropathy. We found
      that of 20 temporal artery biopsies that had been performed on this group, only 4
      were reported to have had positive results. On re-examination of pathologic
      specimens, 1 of the 4 was found not to meet the latest pathologic criteria for
      this disease, leaving only 3 cases of biopsy-proven giant cell arteritis. The
      calculated incidence of giant cell arteritis in the Alaska Native population is
      approximately 1/100,000 in those over 50 years old. CONCLUSIONS: Compared with
      previous epidemiologic studies performed worldwide, our review suggests a very
      low incidence of biopsy-proven giant cell arteritis among Alaska Natives.

PMID- 19169315
TI  - Stereotactic radiotherapy in the treatment of juxtapapillary choroidal melanoma:
      2-year follow-up.
AB  - OBJECTIVE: To evaluate the efficacy and complications of stereotactic
      radiotherapy in the management of patients with juxtapapillary choroidal
      melanoma. DESIGN: Retrospective review. PARTICIPANTS: 64 patients with
      juxtapapillary choroidal melanoma. METHODS: Consecutive patients with
      juxtapapillary choroidal melanomas located within 2 mm of the optic nerve,
      treated with stereotactic radiotherapy at Princess Margaret Hospital from October
      1998 to January 2006, were reviewed for treatment effect and complication rates.
      RESULTS: Median age was 63 years. Median tumor height was 4.2 mm, and median
      maximum tumor diameter was 9.8 mm. The prescribed radiation dose was 70 Gy in 5
      fractions over 10 days, and the median follow-up was 26 months. After treatment,
      there was local tumor recurrence in 3 patients, and in 8 patients there was
      systemic progression. Actuarial rates of local tumor control, metastases, and
      survival at 26 months were 94%, 12%, and 94%, respectively. Rates of radiation
      induced neovascular glaucoma, cataract, retinopathy, and optic neuropathy at 26
      months were 28%, 45%, 80%, and 52%, respectively. Enucleation was necessary for 7
      patients. CONCLUSIONS: Stereotactic radiotherapy offers a noninvasive alternative
      with acceptable ocular toxicity rates to enucleation and brachytherapy in the
      management of juxtapapillary choroidal melanoma.

PMID- 19169316
TI  - Knowledge about glaucoma and barriers to follow-up care in a community glaucoma
      screening program.
AB  - OBJECTIVE: To assess perceived barriers to glaucoma follow-up care, including the
      lack of glaucoma knowledge and the lack of health care access, among participants
      in a community glaucoma screening program. DESIGN: Community survey.
      PARTICIPANTS: Two hundred forty-three consecutive participants in a series of
      free glaucoma screenings between November 2002 and August 2003. METHODS: The
      survey consisted of 20 questions designed to elicit knowledge of glaucoma and
      perception of potential barriers to follow-up care. Our aim was to find
      correlations between patient demographics and knowledge of glaucoma as well as
      perceived potential barriers to follow-up care. The data were analyzed using
      SPSS, v. 10.1. RESULTS: The average age of the respondents was 70 years, and
      females predominated (66%). About half of the respondents knew of an eye doctor
      in their neighborhood, and 60% had had an eye examination in the past year. Two
      hundred twenty-two (91%) indicated they could get to an eye doctor if the
      screening examination indicated they needed a follow-up examination. Two hundred
      twenty (90.5%) had medical insurance. One hundred seventy-eight (73%) of the
      participants had heard of glaucoma; 71 (29%) identified an accurate definition of
      glaucoma. The level of education and the language spoken at home were correlated
      with both glaucoma awareness (p < 0.001; p < 0.001) and knowledge of an accurate
      definition of glaucoma (p < 0.001; p < 0.025). CONCLUSIONS: In this population, a
      lack of adequate education about glaucoma may be more significantly associated
      with poor follow-up rates than a lack of access to care in those identified as
      glaucoma suspects.

PMID- 19169317
TI  - Biometric characteristics of eyes with exfoliation syndrome and occludable as
      well as open angles and eyes with primary open-angle glaucoma.
AB  - OBJECTIVE: To describe differences in axial length scan (A-scan) and ultrasound
      biomicroscopy (UBM) parameters in eyes with exfoliation syndrome (XFS) and
      occludable angles (XFSOc), XFS and open angles (XFSOp), and eyes with primary
      open-angle glaucoma (POAG). DESIGN: Cross-sectional descriptive study.
      PARTICIPANTS: Seventy-two eyes of 72 patients (mostly Caucasians) were identified
      through glaucoma clinics at the University of Ottawa;19 eyes had XFSOc, 31 eyes
      XFSOp, and 22 eyes POAG. METHODS: After a detailed ophthalmic history and
      examination, A-scan biometry and UBM were done to assess anterior segment
      parameters: central anterior chamber depth (ACD), lens thickness, trabecular
      meshwork-iris angle, and angle opening distance (AOD). Lens/axial length factor
      and the relative lens position were calculated. The above measurements were
      compared across the 3 groups. RESULTS: We found statistically significant
      differences in measurements among the groups. ACD was shallowest in eyes with
      XFSOc (1.88 [SD 0.07] mm), followed by XFSOp (2.37 [SD 0.05] mm), and POAG (2.64
      [SD 0.08] mm). XFSOc had thicker lenses (5.28 [SD 0.09] mm) compared with the
      other groups: XFSOp (5.03 [SD 0.06] mm) and POAG (4.84 [SD 0.09] mm). Lens/axial
      length factor was highest in XFSOc (2.34 [SD 0.05] mm) versus XFSOp (2.12 [SD
      0.03] mm) and POAG (2.02 [SD 0.05] mm); relative lens position was lowest in
      XFSOc (2.27 [SD 0.03] mm) versus XFSOp (2.31 [SD 0.02] mm) and POAG (2.36 [SD
      0.03] mm). CONCLUSIONS: Eyes with XFSOc in our study demonstrated lens thickening
      and shallow central ACD versus eyes with XFSOp and eyes with POAG. This suggests
      the possibility that cataract formation and (or) zonular weakness may contribute
      to the development of an occludable angle in eyes with XFS.

PMID- 19169318
TI  - Efficacy and tolerability of nonpenetrating glaucoma surgery augmented with
      mitomycin C in treatment of open-angle glaucoma: a meta-analysis.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of nonpenetrating glaucoma
      surgery (NPGS) augmented with mitomycin C (MMC) compared with trabeculectomy (TE)
      plus MMC in the treatment of patients with open-angle glaucoma. DESIGN:
      Systematic review and meta-analysis. PARTICIPANTS: Eight clinical trials,
      including 4 cohort and 4 randomized, enrolled 459 eyes. METHODS: Pertinent
      studies were selected through extensive searches of the Cochrane Library,
      MEDLINE, EMBASE, and meeting abstracts. Efficacy measures were weighted mean
      differences (WMDs) for the percentage intraocular pressure (IOP) reduction and
      relative risks (RRs) for success rates. Tolerability measures were RRs for
      adverse events. Pooled estimates were carried out in RevMan software v. 4.2.
      RESULTS: NPGS augmented with MMC was associated with a numerically smaller but
      nonsignificant percentage reduction in IOP compared with TE plus MMC, with a WMD
      of -1.27% (95% CI -5.61 to 3.07) at 1 year, -4.55% (-10.35 to 1.24) at 2 years, 
      0.82% (-8.80 to 7.17) at 3 years, and -6.16% (-25.97 to 13.65) at 4 years.
      Significantly greater proportions of TE plus MMC patients than NPGS augmented
      with MMC patients achieved the target IOP without antiglaucoma medication at the
      end point, with a pooled RR of 0.74 (0.63-0.86). NPGS augmented with MMC was
      associated with a significantly lower frequency of shallow anterior chamber and
      cataract than TE plus MMC, with pooled RRs of 0.31 (0.16-0.60) and 0.23 (0.11
      0.47), respectively. CONCLUSIONS: NPGS augmented with MMC was associated with IOP
      lowering efficacy comparable to that of TE plus MMC. However, significantly fewer
      patients achieved the target IOP with NPGS augmented with MMC than with TE plus
      MMC. NPGS augmented with MMC was better tolerated than TE plus MMC.

PMID- 19169319
TI  - A controlled clinical interventional trial comparing 2% chloroprocaine
      bupivicaine versus 2% lidocaine-bupivicaine for retrobulbar anesthesia in scleral
      buckling surgery.
AB  - OBJECTIVE: We undertook this prospective study to compare the relative
      effectiveness of a bupivicaine mixture with either lidocaine or chloroprocaine
      for retrobulbar anesthesia in scleral buckling surgery, since chloroprocaine, in
      some types of nonocular nerve block anesthesia, has been demonstrated to be a
      more effective nerve block anesthetic. DESIGN: This prospective, randomized,
      double-blind, controlled, clinical, unicentre, interventional trial compared
      mixtures of lidocaine-bupivacaine with chloroprocaine-bupivacaine in scleral
      buckling surgery performed by 1 surgeon during a 12-month period. PARTICIPANTS: A
      total of 136 patients who underwent scleral buckling surgery constituted the
      cases studied. METHODS: A total of 31 variables comprising surgical, anesthetic,
      and patient-centered data were analyzed to determine which drug combination was
      more efficacious. RESULTS: No statistically significant differences were found
      between chloroprocaine and lidocaine mixtures for retrobulbar anesthesia in
      scleral buckling surgery from the point of view of the surgeon, anesthetist, or
      patient. CONCLUSIONS: We found no difference in effectiveness for bupivicaine
      mixed with either lidocaine or chloroprocaine for retrobulbar anesthesia in
      scleral buckling surgery. Surgeon, anesthetist, and patient-centered data showed
      no differences in any of the measures studied.

PMID- 19169320
TI  - Incidence and outcome of endophthalmitis over a 13-year period.
AB  - OBJECTIVE: The aim of the study was to assess the functional results and long
      term visual prognosis in patients treated for acute endophthalmitis (AE). DESIGN:
      Observational clinical series. PARTICIPANTS: Evaluation of 120 eyes of 114
      patients with AE treated between 1991 and 2004. METHODS: This retrospective
      institutional analysis included 120 eyes of 114 patients (52 male, 68 female)
      with AE and a minimum follow-up of half a year. The patients had a mean follow-up
      of 23 months (6-135 months) and a mean age of 61 years (8 months-94 years) at the
      time of treatment. Treatment included intraocular injection of antibiotics alone
      (n = 18, 15%) and vitrectomy combined with intraocular and topical postoperative
      antibiotics (n = 85, 70%). RESULTS: The most frequent complications were vitreous
      or retinal hemorrhages (n = 17, 14%), retinal detachment (n = 17, 14%), choroidal
      detachment (n = 3, 3%), secondary glaucoma (n = 7, 6%), and recurrent
      endophthalmitis (n = 3, 3%). Four eyes had to be enucleated because of recurrent
      and uncontrollable infection. Positive microbiological results were achieved in
      67 of 88 specimens (76%). The most common isolate was Staphylococcus. At the end
      of follow-up, visual acuity was reduced (more than 2 lines) in 18 eyes (15%),
      stable in 22 (18%), and improved (more than 2 lines) in 72 eyes (60%).
      CONCLUSIONS: AE is a rare but severe disease with a potentially deleterious
      outcome in affected eyes. In our series, 78% of all eyes had stable or improved
      postoperative visual acuity following various treatment regimens, depending on
      the severity of each case.

PMID- 19169321
TI  - Delayed in-the-bag implantation of intraocular lens.
AB  - OBJECTIVE: To report delayed in-the-bag intraocular lens (IOL) implantation for
      patients who had undergone simultaneous phacoemulsification and vitreoretinal
      surgery. DESIGN: Interventional case series. PARTICIPANTS: Delayed IOL
      implantation surgery was performed for 3 patients who had undergone simultaneous
      phacoemulsification and scleral buckling or vitrectomy surgery. METHODS: The
      medical records of each patient, including the surgical findings and final
      refraction status, were reviewed retrospectively. RESULTS: Successful in-the-bag
      IOL implantation surgeries without capsular tear were achieved 3 to 5 months
      after the initial surgeries. The postoperative refractive error ranged from plano
      to -1.00 D. CONCLUSIONS: Successful in-the-bag IOL implantation and satisfactory
      refraction were achieved in patients who had undergone simultaneous
      phacoemulsification and scleral buckling or vitrectomy surgery.

PMID- 19169322
TI  - Canadian clinical practice guidelines for cataract surgery.

PMID- 19169324
TI  - Diabetic retinopathy screening.

PMID- 19169325
TI  - Orbital wall infarction versus infection in sickle cell disease.

PMID- 19169326
TI  - Posterior capsular rupture secondary to viscoelastic cannula and luer-lock
      release during phacotrabeculectomy.

PMID- 19169328
TI  - Recurrent Meesmann's corneal dystrophy: treatment with keratectomy and mitomycin
      C.

PMID- 19169329
TI  - Unsuspected adenocarcinoma of the nonpigmented ciliary epithelium in a blind
      painful eye.

PMID- 19169330
TI  - Intracameral bevacizumab in the treatment of neovascular glaucoma and exudative
      retinal detachment after brachytherapy in choroidal melanoma.

PMID- 19169331
TI  - Treatment of macular hole contiguous with pigment epithelial detachment.

PMID- 19169332
TI  - False-negative apraclonidine testing in acute Horner syndrome.

PMID- 19169333
TI  - Acute comitant esotropia secondary to idiopathic intracranial hypertension in a
      child receiving recombinant human growth hormone.

PMID- 19169334
TI  - Nineteen-year delayed-onset phacolytic uveitis following dislocation of the
      crystalline lens.

PMID- 19169336
TI  - Selenium and aspirin in people living with HIV and AIDS in Nigeria.
AB  - OBJECTIVES: Aspirin and selenium have been shown in vitro and in vivo to inhibit
      HIV production through inhibition of the transcription factor, the nuclear factor
      kappa binding (NF-eB). The aim of this study was to examine the efficacy or
      otherwise of these drugs in people living with HIV and AIDS (PLWAS) in resource
      limited countries. PATIENTS AND METHODS: Consenting HAART-naive PLWAS with mean
      CD4 count of 256.8 +/- 67.6 cells/ul were recruited into the study. Pretherapy
      blood count, serum biochemistry, chest x-ray, urinary glucose and protein and
      microscopy and culture of both urine and stool were checked in all cases. Each
      patient was treated for six months and CD4 counts were repeated at the end of the
      study. Thirty two patients (23 (72%) females and nine (28%) males), aged 22-52
      (median = 36) years were recruited. Twenty-three (72%) were randomised into
      selenium and aspirin (SAM) and nine (28%) into selenium (SM); multivitamin was
      added to each arm. RESULTS: Eighteen (56.2%) patients completed the study.
      Sixteen (88.9%) patients are already on HAART since the termination of the study;
      one absconded and one died of disease progression. Fourteen (43.8%) of the
      initial 32 patients dropped out (11 (78.6%) were lost to follow-up, two (14.3%)
      died and one (7.1%) opted for HAART before completing the study). The post
      treatment CD4 count was 293.0 +/-102.2 cells/ml, compared to the pre-therapy mean
      of 256.8 +/- 67.6 cells/ul, an average rise of 36.2 cells/ul, the difference was
      not statistically significant (p = 0.059). The post-therapy mean weight was
      significantly higher than the pretherapy weight, 61.6+/-15.2 kg versus 60.0+/
      14.3 kg (p = 0.015). CONCLUSION: The SAM/SM combination regimen improved the
      quality of life of PLWAS, however, a greater number of patients and a longer
      period of follow up, are necessary to arrive at a more meaningful conclusion.

PMID- 19169337
TI  - Serum concentration of acute phase protein and lipid profile in HIV-1
      seropositive patients and its relationship to the progression of the disease.
AB  - AIMS AND OBJECTIVES: To evaluate the effect of HIV-1 infection and its
      progression on lipid profiles, acute-phase proteins and to determine which of the
      parameters may serve as an early indicator of the progression of HIV infection.
      MATERIALS AND METHODS: A cross-sectional study was conducted on sixty-two HIV-1
      infected subjects attending HIV clinic, the patients consisted of 29 males and 33
      females aged between 20-60 years (mean age 31+/- 7 years) who were screened for
      HIV-1 by ELISA test. Absolute CD4+ T lymphocyte was counted and HIV infected
      individuals were classified according to the Centre for Disease Control and
      Prevention (CDC) Criteria; CD4+ counts e"500/mm3 (asymptomatic), CD4+ counts 200
      499/mm3 (symptomatic) and CD4+ counts d"199/mm3 (symptomatic) with full blown
      AIDS. Serum concentrations of total protein, albumin, gamma globulin, acute-phase
      protein, and lipid profile were determined. RESULTS: There was significantly
      increased gamma globulin fraction of the serum protein in HIV patients with CD4+
      counts of e"500/mm3, 200-499/mm3 and d"199/mm3 when compared with the controls.
      Serum triglyceride was significantly increased in HIV patients with CD4+ counts
      of d"199/mm3 only, whereas a significantly decreased serum HDL-cholesterol in HIV
      patients with CD4+ counts of 200-499/mm3 and d"199/mm3 was found when compared
      with the controls. Haptoglobin, C-reactive protein and a1-acid glycoprotein were
      significantly increased in HIV patients with CD4+ counts of 200-499/mm3 and
      d"199/mm3 when compared with the controls. However, albumin was significantly
      reduced in HIV patients with CD4+ counts of d"199/mm3 when compared with the
      controls. There was direct correlation between HDL-cholesterol and the CD4+
      counts, on the other hand, an inverse correlation between C-reactive protein,
      haptoglobin and a1-acid glycoprotein against CD4+ counts was found. CONCLUSION: A
      decreased HDL-cholesterol had direct correlation with the CD4+ counts in all the
      stages of HIV infection; however, increased haptoglobin and C-reactive protein
      had inverse correlation with the CD4+ counts in all the stages of HIV infection.
      Therefore HDL-cholesterol, C-reactive protein and haptoglobin may serve as
      indicators of disease progression in HIV infection.

PMID- 19169338
TI  - Effects of chronic administration of vitamin E on haemodynamic responses to
      postural stress or cold pressor test in apparently healthy young men.
AB  - OBJECTIVES: We sought to investigate the possible effect of chronic
      administration of vitamin E on haemodynamic responses to sympathetic stimulation
      and to test the hypothesis that chronic administration of vitamin E increases
      susceptibility to orthostatic intolerance. METHODS: Sympathetic stimulation was
      assessed by responses in systolic blood pressure (SBP), diastolic blood pressure
      (DBP), mean arterial pressure (MAP), heart rate (HR), forearm blood flow (FBF;
      venous occlusion plethysmography) and forearm vascular resistance (FVR) evoked by
      postural stress (600 head-up tilt; HUT) or cold pressor test (CPT) in 30 healthy
      young men before and after 4 weeks of vitamin E administration. CPT was induced
      by immersing a hand in water at 40 degrees C for 2 minutes. RESULTS:
      Administration of vitamin E reduced SBP (p<0.001), DBP (p<0.001), MAP (p<0.001),
      HR (p<0.001) and FVR (p<0.05) but increased FBF (p<0.01). Before vitamin E
      administration HUT increased HR (p<0.001). Conversely, HUT led to a decrease in
      HR (p<0.05) after vitamin E administration. The decreases in SBP (p<0.05) and FBF
      (p<0.05) with concomitant increases in DBP (p<0.001), MAP (p<0.001) and FVR
      (p<0.001) induced by HUT before vitamin E administration, were similar to those
      induced by HUT after vitamin E administration. The increases in SBP (p<0.001),
      DBP (p<0.001), MAP (p<0.001), HR (p<0.05), FVR (p<0.001) and a decrease in FBF
      (p<0.001) induced by CPT before vitamin E administration, were attenuated
      following vitamin E administration in these subjects. CONCLUSION: These results
      demonstrate that chronic administration of vitamin E significantly reversed HUT
      induced tachycardia and prevented CPT-induced vascular and pressor responses.
      These findings suggest that vitamin E may exert cardioprotective effect
      presumably through enhanced cardiac vagal tone that may not be associated with
      poor orthostatic tolerance in young men.

PMID- 19169339
TI  - Splenic enlargement and abdominal scarification in childhood malaria. Beliefs,
      practices and their possible roles in management in Benin City, Nigeria.
AB  - BACKGROUND: To achieve sustainable reduction in malaria burden in Africa,
      cultural practices that foster increased malaria burden must be addressed. In Edo
      state Nigeria, scarification/tattooing on the left hypochondrium presumably over
      an enlarged spleen arising mainly from malaria is widely practiced. This practice
      is deleterious, diversionary and causes complications. AIMS AND OBJECTIVES: This
      was a cross-sectional and descriptive study to evaluate the beliefs and practice,
      regarding abdominal wall scarification in children and within the context of
      malaria control; It was carried out among experienced women in child care
      selected from Egor Local Government Area of Edo State, Nigeria. METHODS:
      Information relating to beliefs, knowledge and their practices including possible
      socio-cultural/economic determinants were obtained with use of questionnaire.
      RESULTS: Of the 400 questionnaires administered 394 were responded to. The modal
      age bracket was 26 - 30 years (Range, 18 - 56 years) Respondents were mainly
      Binis Esan and Ibos amongst others. About 27.0% of respondents considered the
      spleen a "bag of worms". Other views included "collection of bad blood" 27.2% and
      as a sickness of its own, 14.7%. Named causes of splenomegaly were fever, 59.6%
      and evil spirit, 15.5%. Over 45.0% of respondents would consult the herbalists
      for splenomegaly. Less educated (X2 = 40.0, p<0.005), women over 40 years of age
      (X2 = 13.5, p< 0.05) and Esan/Bini ethnic groups (X2 = 15.6, p <0.05) are more
      prone to the practice. Reasons for widespread use included perceived
      effectiveness, low cost and accessibility. Information on scarification was
      obtained mainly from family members, 49.5%, neighbours, 25.1%; and
      friends/colleagues, 16.7% CONCLUSION/RECOMMENDATIONS: Practice of scarification
      is deep rooted and widespread in the study location. It has potentials to negate
      efforts involved in malaria control. Education including public enlightenment
      campaign should effectively check the practice.

PMID- 19169340
TI  - Experience with prosthetic reconstruction of ear defects at LUTH, Lagos, Nigeria.
AB  - AIM: The aim of the article is to report our experience with prosthetic
      reconstruction of ear defects in Nigerians. MATERIALS AND METHODS: A review of
      all consecutive cases of alloplastic (prosthesis) reconstruction of auricular
      defects was conducted at the Department of Oral and Maxillofacial Surgery of the
      Lagos University Teaching Hospital. Data collected included age and sex of
      patients, aetiology of defects, site of defects (left or right), lost tissue
      (partial or total), material used for the fabrication, and mode of retention of
      the prosthesis. RESULTS: A total of 33 consecutive patients who had prosthetic
      reconstruction of auricular defects during the period were included. The male-to
      female ratio was 3.7: 1. Six cases (18.2%) were congenital defects and 27 (81.8)
      cases were acquired defects. Three (50%) of the congenital cases were microtia.
      Majority (63%) of the acquired cases were due to road traffic crashes. Total loss
      of the auricle was recorded in 22 (66.7%) patients. Of the patients with partial
      loss of the auricle, pinna was the major structure lost in 5 patients while pinna
      +lobe were lost in another 5 patients. Silicone elastomers was the most
      frequently used material for the fabrication of auricular prostheses (29
      patients). The most frequently used retention method was silastic medical grade
      adhesive. CONCLUSIONS: Prosthetic option is a valuable technique for the
      reconstruction of ear defect. The primary indication for prosthetic
      reconstruction of ear defect in the present study is acquired ear deformity;
      mainly due to road traffic crashes.

PMID- 19169341
TI  - Review of the histopathologic patterns of superficial lymph node diseases, in
      Lagos (1991-2004).
AB  - OBJECTIVE: This is a 14-year retrospective histopathologic study of 720 lymph
      node biopsies. The aim is to document the causes of lymphadenopathy, the age and
      sex distribution in Lagos. MATERIALS AND METHODS: The materials consisted of
      slides and paraffin embedded blocks of all lymph node biopsy specimens received
      from within and outside Lagos University Teaching Hospital, Lagos. RESULTS: A
      total of 720 biopsies from 276 males and 444 females were analysed. Chronic non
      specific lymphadenitis 245 (34%), tuberculosis 125 (17.4%), metastatic lymph node
      lesions 242 (33.6%), and lymphomas 102(14.2%) were the common causes of lymph
      node enlargement. The commonest lymph node group affected was the cervical 283
      (39.3%). CONCLUSION: Malignancy (47.8%) is the most common cause of superficial
      lymphadenopathy in Lagos metropolis. The age, sex and site prevalence agree with
      reports from other parts of Nigeria and Africa with minimal variations.

PMID- 19169342
TI  - Causes and pattern of death in a tertiary health institution in South Western
      Nigeria.
AB  - OBJECTIVE: The study reviewed and analysed the causes and pattern of death among
      patients admitted to the Federal Medical Centre, Owo in the year 2004. PATIENTS
      AND METHODS: The case note records of all patients that died on admission in the
      hospital for the year 2004 were reviewed. A total of 104 cases out of the 114
      patients that died were reviewed. Total admission was 1819 for the year. RESULTS:
      Annual death rate was 6.3%. Overall, infectious causes of death was the most
      common (22.1%) ; this was followed by deaths from pregnancy and neonatal preterm
      related causes(18.3%) while deaths from neurological disorders (stroke,
      meningitis, and meningo-encephalitis among others) (17.3%); gastro-intestinal
      disorders(11.6%), respiratory disorders (10.6%) endocrine disorders (7.7%) and
      others followed in that order. In the medical wards cerebrovascular disease was
      the leading cause of death; in Obstetrics and Gynaecology, prolonged obstructed
      labour was the leading cause of death while Paediatrics and Surgery departments
      had preterm births and head injuries and multiple fractures as the leading causes
      of death respectively. CONCLUSIONS: Periodic review of hospital deaths could be
      important in knowing the changing pattern of mortality in our environment. In
      this study, improvement in the living condition of the citizens, use of potent
      antibiotics in treating infections and increased patronage of immunisation
      facilities as ways of control of infections is advocated.

PMID- 19169343
TI  - Mechanisms of orbital blowout fracture: a critical review of the literature.
AB  - OBJECTIVE: The aim of the present study is to critically review relevant
      literature regarding the mechanism of blowout fractures of the orbit and provide
      an answer to the question: Can one theory adequately explain the mechanism of
      orbital blowout fractures in the light of present day knowledge? MATERIALS AND
      METHODS: A computerised literature search using MEDLINE was conducted for
      published articles on orbital blowout fractures. Mesh phrases used in the search
      were: orbital blowout fractures AND mechanisms; orbital blowout fractures AND
      theory; orbital wall injury AND mechanisms. Only relevant articles were selected
      for the review. RESULTS: The physical mechanism of orbital blowout fracture has
      been a subject of debate for years by maxillofacial surgeons, ophthalmologists,
      plastic surgeons, otolaryngologists and orbitologists. However, only 3 mechanisms
      of injury have been proposed namely: "hydraulic" theory, "globe-to-wall" theory
      and "bone conduction" theory. Most of the theories of orbital blowout fractures
      have been confirmed through brilliant experiments and hypothetical
      explanation/analysis of clinical and radiologic findings, and each one appears to
      fit according to the different type of trauma received. CONCLUSIONS: Based on
      contemporary evidence, one theory may not adequately explain all types of
      fractures completely or be responsible exclusively in a given case for the
      pattern of fracture observed. Blowout fractures of the orbit could therefore be
      due to a combination of 2 or more mechanisms.

PMID- 19169344
TI  - Experience on Transfontanelle Neurosonography in Kano, Nigeria: a preliminary
      report.
AB  - OBJECTIVE: To retrospectively audit and analyse all the Transfontanelle
      Neurosonographic scans performed at the Aminu Kano Teaching Hospital (AKTH),
      between January to September, 2004. METHODS: Information on the gray scale
      appearance of the ventricles, cerebral and cerebellar parenchyma, extra axial
      fluid spaces, status of the sulci and gyri and the echogenic internal outline of
      the bony skull vault was extracted from the records of all the Transfontanelle
      neurosonographic scans performed at the specialist Ultrasound clinic of the AKTH,
      between January to September, 2004. RESULTS: Eighteen infants were scanned, and 8
      (44.4%) of them were neonates. Meningitis (9 patients) and increasing head size
      (7 patients) were the commonest clinical indication for referral. Communicating
      hydrocephalus was the only known complication seen in 4(44.4%) of the post
      meningitic patients. While in the increasing head size group, congenital
      malformations such as Aqueductal stenosis and Arachnoid cyst of the quadrigeminal
      cistern as well as hydrocephalus predominates (4 out of 7 patients). The last 2
      patients referred on account of severe birth asphyxia and swollen occiput showed
      no abnormality and occipital meningocoele respectively. CONCLUSION: This study
      confirms the earlier notion of the pre-eminence of infection as compared to
      congenital malformation as the leading cause of infant morbidity in developing
      nations. It also emphasises the value of Transfontanelle neurosonography as an
      excellent, non-invasive, inexpensive, rapid and safe imaging modality for the
      evaluation of the pathologic conditions of infants' brain.

PMID- 19169345
TI  - Relationship of National Institute of Health Stroke Scores [NIHSS] to 90 days
      mortality in Africa.
AB  - OBJECTIVE: The prognostic value of the NIHSS score has not been evaluated in
      Africans. The study objective was to compare the NIHSS score at presentation to
      mortality and prognosis in survivors. METHODS: We studied 87 patients with acute
      ischaemic stroke. Their presenting NIHSS score, Clinical features including
      complications were recorded on admission. Mortality and outcome within 90 days
      were evaluated using Glasgow Outcome scale. RESULTS: Patients with NIHSS score of
      20 and above had mortality of 56.5%, all survivors had severe disability: NIHSS
      score between 15-19, mortality was 30% and of survivors, 42.8% had severe
      disability, 33.7% moderate disability and 14.2% recovered completely. With NIHSS
      score between 6-14, mortality was 24.9% and of survivors, 13.3% had severe
      disability, 36.6% moderate disability and 50% had good recovery. With NIHSS score
      of 5 or less there were no deaths and of survivors, 30% had moderate disability
      and 70% good recovery. It was however observed that if initial NIHSS score
      remained static or worsened, prognosis was worse. Among such patients those with
      initial NIHSS score of 20 and above all died, compared with those with NIHSS
      score of less than 20 who had mortality of 70%. CONCLUSION: The 30th day
      mortality index was the best predictor of mortality. High mortality were observed
      in patients with NIHSS scores 20 and above, presence of neurological
      complications and static baseline scores. After 90 days, good outcome was
      observed in patients with the least scores and severe disability in high score
      survivors.

PMID- 19169346
TI  - Typical and atypical presentations of congenital diaphragmatic hernia - a report
      of 2 cases.
AB  - Congenital diaphragmatic hernias occur through embryologic defects in the
      diaphragm. We present 2 cases of congenital diaphragmatic hernia, the first case
      was a late presentation in an 11 month old child, and the second case was an
      early typical presentation in a day old child, both diagnoses were made on chest
      radiographs. The paper is focused on the key role of the radiologist in a
      resource poor environment to make early diagnosis of this fatal and rare
      condition. Early diagnosis of this defect is essential. This will allow timely
      intervention and appropriate management, therefore, reducing the mortality
      associated with the condition.

PMID- 19169347
TI  - Ovarian non-Hodgkin's lymphoma presenting as obstructive jaundice - a case
      report.
AB  - OBJECTIVE: To highlight the importance of considering abdominal Lymphoma as a
      differential diagnosis in the management of obstructive jaundice. PATIENT: A 51
      year old female who presented with abdominal swelling associated with features of
      obstructive jaundice. Significant findings included jaundice on examination, with
      abdominal ascites. Laparotomy revealed three litres of icteric fluid. There was a
      huge left ovarian tumour measuring 14 cm x 12 cm. Massive peritoneal seedling
      involved the whole abdomen and pelvis was noted. Following surgery allowing for
      adequate wound healing, the patient was placed on appropriate chemotherapy.
      INVESTIGATION/DIAGNOSIS: Histology of excision biopsy revealed high grade Non
      Hodgkins's Lymphoma. Screening for human deficiency virus (HIV) was negative.
      However the erythrocyte sedimentation rate (ESR) was raised at 92 mm Westergren
      in the first hour. The liver function tests were deranged with total bilirubin of
      274 micromol/l and conjugated bilirubin of 204 micromol. serum Ast and Alt were
      also significantly raised. Total proteins, urea and electrolytes remained
      essentially within normal limits. The patient was placed on CHOP combination
      therapy. She attained remission after four cycles of chemotherapy and was
      discharged home. CONCLUSION: Abdominal Non-Hodgkin's Lymphoma should be a strong
      consideration in the management of obstructive jaundice.

PMID- 19169348
TI  - Intracystic papillary carcinoma of the breast in a Nigerian male: case report.
AB  - Intracystic papillary non invasive breast carcinoma is an extremely rare form of
      intraductal carcinoma constituting 5% of male breast cancer. The latter accounts
      for only 1% of all breast cancers. Until now, no case has been documented in an
      African male. This tumour was found in an 86 year-old male. It appeared benign on
      physical examination. Fine needle aspiration cytology was inaccurate. However,
      excisional biopsy in the form of total mastectomy with axillary clearance served
      to diagnose as well as treat the disease. This may be the first case of
      intracystic papillary carcinoma of the breast in the Nigerian male.

PMID- 19169349
TI  - Rickets of prematurity- a case report.
AB  - OBJECTIVE: This case report seeks to create awareness of the aetiology of rickets
      of prematurity among very low birth weight infants in Nigeria METHODS AND RESULT:
      This is a case report of an 800 gramme premature male neonate delivered by
      caesarean section at 28 weeks gestation following severe maternal pre-eclampsia.
      The infant was hospitalised for sixty days and fed exclusively on his mother's
      breast milk for seven months. He had two episodes of sepsis and was transfused
      twice while on admission. He was on Abidec drops, which contained 400 IU/0.6 ml
      of vitamin D from the age of two weeks. He defaulted from the follow up clinic at
      postnatal age of 16 weeks only to reappear at 30 weeks postnatal age with overt
      clinical, biochemical and radiologic signs of rickets. He responded well to
      calcium and phosphate supplementation. CONCLUSION: This case highlights the role
      of mineral deficiency in the aetiology of rickets of prematurity in very low
      birth weight infants fed with their mothers' breast milk.

PMID- 19169350
TI  - A python analytical pipeline to identify prohormone precursors and predict
      prohormone cleavage sites.
AB  - Neuropeptides and hormones are signaling molecules that support cell-cell
      communication in the central nervous system. Experimentally characterizing
      neuropeptides requires significant efforts because of the complex and variable
      processing of prohormone precursor proteins into neuropeptides and hormones. We
      demonstrate the power and flexibility of the Python language to develop
      components of an bioinformatic analytical pipeline to identify precursors from
      genomic data and to predict cleavage as these precursors are en route to the
      final bioactive peptides. We identified 75 precursors in the rhesus genome,
      predicted cleavage sites using support vector machines and compared the rhesus
      predictions to putative assignments based on homology to human sequences. The
      correct classification rate of cleavage using the support vector machines was
      over 97% for both human and rhesus data sets. The functionality of Python has
      been important to develop and maintain NeuroPred
      (http://neuroproteomics.scs.uiuc.edu/neuropred.html), a user-centered web
      application for the neuroscience community that provides cleavage site prediction
      from a wide range of models, precision and accuracy statistics, post
      translational modifications, and the molecular mass of potential peptides. The
      combined results illustrate the suitability of the Python language to implement
      an all-inclusive bioinformatics approach to predict neuropeptides that
      encompasses a large number of interdependent steps, from scanning genomes for
      precursor genes to identification of potential bioactive neuropeptides.

PMID- 19169351
TI  - Genetic editing of HBV DNA by monodomain human APOBEC3 cytidine deaminases and
      the recombinant nature of APOBEC3G.
AB  - Hepatitis B virus (HBV) DNA is vulnerable to editing by human cytidine deaminases
      of the APOBEC3 (A3A-H) family albeit to much lower levels than HIV cDNA. We have
      analyzed and compared HBV editing by all seven enzymes in a quail cell line that
      does not produce any endogenous DNA cytidine deaminase activity. Using 3DPCR it
      was possible to show that all but A3DE were able to deaminate HBV DNA at levels
      from 10(-2) to 10(-5)in vitro, with A3A proving to be the most efficient editor.
      The amino terminal domain of A3G alone was completely devoid of deaminase
      activity to within the sensitivity of 3DPCR ( approximately 10(-4) to 10(-5)).
      Detailed analysis of the dinucleotide editing context showed that only A3G and
      A3H have strong preferences, notably CpC and TpC. A phylogenic analysis of A3
      exons revealed that A3G is in fact a chimera with the first two exons being
      derived from the A3F gene. This might allow co-expression of the two genes that
      are able to restrict HIV-1Deltavif efficiently.

PMID- 19169352
TI  - Effect of testosterone on insulin stimulated IRS1 Ser phosphorylation in primary
      rat myotubes--a potential model for PCOS-related insulin resistance.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by a
      hyperandrogenic state and frequently develops skeletal muscle insulin resistance.
      We determined whether testosterone adversely affects insulin action by increasing
      serine phosphorylation of IRS-1(636/639) in differentiated rat skeletal muscle
      myotubes. The phosphorylation of Akt, mTOR, and S6K, downstream targets of the
      PI3-kinase-IRS-1 complex were also studied. METHODS: Primary differentiated rat
      skeletal muscle myotubes were subjected to insulin for 30 min after 16-hour pre
      exposure to either low (20 ng/ml) or high (200 ng/ml) doses of testosterone.
      Protein phosphorylation of IRS-1 Ser(636/639), Akt Ser(473), mTOR-Ser(2448), and
      S6K-Thr(389) were measured by Western blot with signal intensity measured by
      immunofluorescence. RESULTS: Cells exposed to 100 nM of insulin had increased IRS
      1 Ser(636/639) and Akt Ser(473) phosphorylation. Cells pre-exposed to low-dose
      testosterone had significantly increased insulin-induced mTOR-Ser(2448) and S6K
      Thr(389) phosphorylation (p<0.05), and further increased insulin-induced IRS-1
      Ser(636/639) phosphorylation (p = 0.042) compared to control cells. High-dose
      testosterone pre-exposure attenuated the insulin-induced mTOR-Ser(2448) and S6K
      Thr(389) phosphorylation. CONCLUSIONS: The data demonstrated an interaction
      between testosterone and insulin on phosphorylation of intracellular signaling
      proteins, and suggests a link between a hyperandrogenic, hyperinsulinemic
      environment and the development of insulin resistance involving serine
      phosphorylation of IRS-1 Ser(636/639). These results may guide further
      investigations of potential mechanisms of PCOS-related insulin resistance.

PMID- 19169353
TI  - Mycobacterium tuberculosis Rv3802c encodes a phospholipase/thioesterase and is
      inhibited by the antimycobacterial agent tetrahydrolipstatin.
AB  - The cell wall of M. tuberculosis is central to its success as a pathogen. Mycolic
      acids are key components of this cell wall. The genes involved in joining the
      alpha and mero mycolates are located in a cluster, beginning with Rv3799c and
      extending at least until Rv3804c. The role of each enzyme encoded by these five
      genes is fairly well understood, except for Rv3802c. Rv3802 is one of seven
      putative cutinases encoded by the genome of M. tuberculosis. In phytopathogens,
      cutinases hydrolyze the waxy layer of plants, cutin. In a strictly mammalian
      pathogen, such as M. tuberculosis, it is likely that these proteins perform a
      different function. Of the seven, we chose to focus on Rv3802c because of its
      location in a mycolic acid synthesis gene cluster, its putative essentiality, its
      ubiquitous presence in actinomycetes, and its conservation in the minimal genome
      of Mycobacterium leprae. We expressed Rv3802 in Escherichia coli and purified the
      enzymatically active form. We probed its activities and inhibitors characterizing
      those relevant to its possible role in mycolic acid biosynthesis. In addition to
      its reported phospholipase A activity, Rv3802 has significant thioesterase
      activity, and it is inhibited by tetrahydrolipstatin (THL). THL is a described
      anti-tuberculous compound with an unknown mechanism, but it reportedly targets
      cell wall synthesis. Taken together, these data circumstantially support a role
      for Rv3802 in mycolic acid synthesis and, as the cell wall is integral to M.
      tuberculosis pathogenesis, identification of a novel cell wall enzyme and its
      inhibition has therapeutic and diagnostic implications.

PMID- 19169354
TI  - Quantitative analysis of peripheral tissue perfusion using spatiotemporal
      molecular dynamics.
AB  - BACKGROUND: Accurate measurement of peripheral tissue perfusion is challenging
      but necessary to diagnose peripheral vascular insufficiency. Because near
      infrared (NIR) radiation can penetrate relatively deep into tissue, significant
      attention has been given to intravital NIR fluorescence imaging.
      METHODOLOGY/PRINCIPAL FINDINGS: We developed a new optical imaging-based strategy
      for quantitative measurement of peripheral tissue perfusion by time-series
      analysis of local pharmacokinetics of the NIR fluorophore, indocyanine green
      (ICG). Time-series NIR fluorescence images were obtained after injecting ICG
      intravenously in a murine hindlimb ischemia model. Mathematical modeling and
      computational simulations were used for translating time-series ICG images into
      quantitative pixel perfusion rates and a perfusion map. We could successfully
      predict the prognosis of ischemic hindlimbs based on the perfusion profiles
      obtained immediately after surgery, which were dependent on the preexisting
      collaterals. This method also reflected increases in perfusion and improvements
      in prognosis of ischemic hindlimbs induced by treatment with vascular endothelial
      growth factor and COMP-angiopoietin-1. CONCLUSIONS/SIGNIFICANCE: We propose that
      this novel NIR-imaging-based strategy is a powerful tool for biomedical studies
      related to the evaluation of therapeutic interventions directed at stimulating
      angiogenesis.

PMID- 19169355
TI  - The tumor suppressor PRDM5 regulates Wnt signaling at early stages of zebrafish
      development.
AB  - PRDM genes are a family of transcriptional regulators that modulate cellular
      processes such as differentiation, cell growth and apoptosis. Some family members
      are involved in tissue or organ maturation, and are differentially expressed in
      specific phases of embryonic development. PRDM5 is a recently identified family
      member that functions as a transcriptional repressor and behaves as a putative
      tumor suppressor in different types of cancer. Using gene expression profiling,
      we found that transcriptional targets of PRDM5 in human U2OS cells include
      critical genes involved in developmental processes, and specifically in
      regulating wnt signaling. We therefore assessed PRDM5 function in vivo by
      performing loss-of-function and gain-of-function experiments in zebrafish
      embryos. Depletion of prdm5 resulted in impairment of morphogenetic movements
      during gastrulation and increased the occurrence of the masterblind phenotype in
      axin+/- embryos, characterized by the loss of eyes and telencephalon.
      Overexpression of PRDM5 mRNA had opposite effects on the development of anterior
      neural structures, and resulted in embryos with a shorter body axis due to
      posterior truncation, a bigger head and abnormal somites. In situ hybridization
      experiments aimed at analyzing the integrity of wnt pathways during gastrulation
      at the level of the prechordal plate revealed inhibition of non canonical PCP wnt
      signaling in embryos overexpressing PRDM5, and over-activation of wnt/beta
      catenin signaling in embryos lacking Prdm5. Our data demonstrate that PRDM5
      regulates the expression of components of both canonical and non canonical wnt
      pathways and negatively modulates wnt signaling in vivo.

PMID- 19169356
TI  - Stress affects a gastrin-releasing peptide system in the spinal cord that
      mediates sexual function: implications for psychogenic erectile dysfunction.
AB  - BACKGROUND: Many men suffering from stress, including post-traumatic stress
      disorder (PTSD), report sexual dysfunction, which is traditionally treated via
      psychological counseling. Recently, we identified a gastrin-releasing peptide
      (GRP) system in the lumbar spinal cord that is a primary mediator for male
      reproductive functions. METHODOLOGY/PRINCIPAL FINDINGS: To ask whether an acute
      severe stress could alter the male specific GRP system, we used a single
      prolonged stress (SPS), a putative rat model for PTSD in the present study.
      Exposure of SPS to male rats decreases both the local content and axonal
      distribution of GRP in the lower lumbar spinal cord and results in an attenuation
      of penile reflexes in vivo. Remarkably, pharmacological stimulation of GRP
      receptors restores penile reflexes in SPS-exposed males, and induces spontaneous
      ejaculation in a dose-dependent manner. Furthermore, although the level of plasma
      testosterone is normal 7 days after SPS exposure, we found a significant decrease
      in the expression of androgen receptor protein in this spinal center.
      CONCLUSIONS/SIGNIFICANCE: We conclude that the spinal GRP system appears to be a
      stress-vulnerable center for male reproductive functions, which may provide new
      insight into a clinical target for the treatment of erectile dysfunction
      triggered by stress and psychiatric disorders.

PMID- 19169358
TI  - On population growth near protected areas.
AB  - BACKGROUND: Protected areas are the first, and often only, line of defense in
      efforts to conserve biodiversity. They might be detrimental or beneficial to
      rural communities depending on how they alter economic opportunities and access
      to natural resources. As such, protected areas may attract or repel human
      settlement. Disproportionate increases in population growth near protected area
      boundaries may threaten their ability to conserve biodiversity.
      METHODOLOGY/PRINCIPAL FINDINGS: Using decadal population datasets, we analyze
      population growth across 45 countries and 304 protected areas. We find no
      evidence for population growth near protected areas to be greater than growth of
      rural areas in the same country. Furthermore, we argue that what growth does
      occur near protected areas likely results from a general expansion of nearby
      population centers. CONCLUSIONS/SIGNIFICANCE: Our results contradict those from a
      recent study by Wittemyer et al., who claim overwhelming evidence for increased
      human population growth near protected areas. To understand the disagreement, we
      re-analyzed the protected areas in Wittemyer et al.'s paper. Their results are
      simply artifacts of mixing two incompatible datasets. Protected areas may
      experience unusual population pressures near their edges; indeed, individual case
      studies provide examples. There is no evidence, however, of a general pattern of
      disproportionate population growth near protected areas.

PMID- 19169357
TI  - Sensing of dietary lipids by enterocytes: a new role for SR-BI/CLA-1.
AB  - BACKGROUND: The intestine is responsible for absorbing dietary lipids and
      delivering them to the organism as triglyceride-rich lipoproteins (TRL). It is
      important to determine how this process is regulated in enterocytes, the
      absorptive cells of the intestine, as prolonged postprandial hypertriglyceridemia
      is a known risk factor for atherosclerosis. During the postprandial period,
      dietary lipids, mostly triglycerides (TG) hydrolyzed by pancreatic enzymes, are
      combined with bile products and reach the apical membrane of enterocytes as
      postprandial micelles (PPM). Our aim was to determine whether these micelles
      induce, in enterocytes, specific early cell signaling events that could control
      the processes leading to TRL secretion. METHODOLOGY/PRINCIPAL FINDINGS: The
      effects of supplying PPM to the apex of Caco-2/TC7 enterocytes were analyzed.
      Micelles devoid of TG hydrolysis products, like those present in the intestinal
      lumen in the interprandial period, were used as controls. The apical delivery of
      PPM specifically induced a number of cellular events that are not induced by
      interprandial micelles. These early events included the trafficking of
      apolipoprotein B, a structural component of TRL, from apical towards secretory
      domains, and the rapid, dose-dependent activation of ERK and p38MAPK. PPM supply
      induced the scavenger receptor SR-BI/CLA-1 to cluster at the apical brush border
      membrane and to move from non-raft to raft domains. Competition, inhibition or
      knockdown of SR-BI/CLA-1 impaired the PPM-dependent apoB trafficking and ERK
      activation. CONCLUSIONS/SIGNIFICANCE: These results are the first evidence that
      enterocytes specifically sense postprandial dietary lipid-containing micelles. SR
      BI/CLA-1 is involved in this process and could be a target for further study with
      a view to modifying intestinal TRL secretion early in the control pathway.

PMID- 19169359
TI  - Inefficient Toll-like receptor-4 stimulation enables Bordetella parapertussis to
      avoid host immunity.
AB  - The recognition of bacterial lipopolysaccharide (LPS) by host Toll-like receptor
      (TLR)4 is a crucial step in developing protective immunity against several gram
      negative bacterial pathogens. Bordetella bronchiseptica and B. pertussis
      stimulate robust TLR4 responses that are required to control the infection, but a
      close relative, B. parapertussis, poorly stimulates this receptor, and TLR4
      deficiency does not affect its course of infection. This led us to hypothesize
      that inefficient TLR4 stimulation enables B. parapertussis to evade host
      immunity. In a mouse model of infection, B. parapertussis grew rapidly in the
      lungs, but no measurable increase in TLR4-mediated cytokine, chemokine, or
      leukocyte responses were observed over the first few days of infection. Delivery
      of a TLR4 stimulant in the inoculum resulted in a robust inflammatory response
      and a 10- to 100-fold reduction of B. parapertussis numbers. As we have
      previously shown, B. parapertussis grows efficiently during the first week of
      infection even in animals passively immunized with antibodies. We show that this
      evasion of antibody-mediated clearance is dependent on the lack of TLR4
      stimulation by B. parapertussis as co-inoculation with a TLR4 agonist resulted in
      10,000-fold lower B. parapertussis numbers on day 3 in antibody-treated wild
      type, but not TLR4-deficient, mice. Together, these results indicate that
      inefficient TLR4 stimulation by B. parapertussis enables it to avoid host
      immunity and grow to high numbers in the respiratory tract of naive and immunized
      hosts.

PMID- 19169361
TI  - Modular Toolkit for Data Processing (MDP): A Python Data Processing Framework.
AB  - Modular toolkit for Data Processing (MDP) is a data processing framework written
      in Python. From the user's perspective, MDP is a collection of supervised and
      unsupervised learning algorithms and other data processing units that can be
      combined into data processing sequences and more complex feed-forward network
      architectures. Computations are performed efficiently in terms of speed and
      memory requirements. From the scientific developer's perspective, MDP is a
      modular framework, which can easily be expanded. The implementation of new
      algorithms is easy and intuitive. The new implemented units are then
      automatically integrated with the rest of the library. MDP has been written in
      the context of theoretical research in neuroscience, but it has been designed to
      be helpful in any context where trainable data processing algorithms are used.
      Its simplicity on the user's side, the variety of readily available algorithms,
      and the reusability of the implemented units make it also a useful educational
      tool.

PMID- 19169360
TI  - Histo-blood group gene polymorphisms as potential genetic modifiers of infection
      and cystic fibrosis lung disease severity.
AB  - BACKGROUND: The pulmonary phenotype in cystic fibrosis (CF) is variable; thus,
      environmental and genetic factors likely contribute to clinical heterogeneity. We
      hypothesized that genetically determined ABO histo-blood group antigen (ABH)
      differences in glycosylation may lead to differences in microbial binding by
      airway mucus, and thus predispose to early lung infection and more severe lung
      disease in a subset of patients with CF. METHODS AND PRINCIPAL FINDINGS: Clinical
      information and DNA was collected on >800 patients with the DeltaF508/DeltaF508
      genotype. Patients in the most severe and mildest quartiles for lung phenotype
      were enrolled. Blood samples underwent lymphocyte transformation and DNA
      extraction using standard methods. PCR and sequencing were performed using
      standard techniques to identify the 9 SNPs required to determine ABO blood type,
      and to identify the four SNPs that account for 90-95% of Lewis status in
      Caucasians. Allele identification of the one nonsynonymous SNP in FUT2 that
      accounts for >95% of the incidence of nonsecretor phenotype in Caucasians was
      completed using an ABI Taqman assay. The overall prevalence of ABO types, and of
      FUT2 (secretor) and FUT 3 (Lewis) alleles was consistent with that found in the
      Caucasian population. There was no difference in distribution of ABH type in the
      severe versus mild patients, or the age of onset of Pseudomonas aeruginosa
      infection in the severe or mild groups. Multivariate analyses of other clinical
      phenotypes, including gender, asthma, and meconium ileus demonstrated no
      differences between groups based on ABH type. CONCLUSIONS AND SIGNIFICANCE:
      Polymorphisms in the genes encoding ABO blood type, secretor or Lewis genotypes
      were not shown to associate with severity of CF lung disease, or age of onset of
      P. aeruginosa infection, nor was there any association with other clinical
      phenotypes in a group of 808 patients homozygous for the DeltaF508 mutation.

PMID- 19169363
TI  - A role for vesicular transport of macromolecules across cell walls in fungal
      pathogenesis.
AB  - In our recent work, we have shown that fungal species from different phyla
      produce extracellular vesicles. The vesicles are heterogeneous and
      morphologically similar to mammalian exosomes, with intact bilayered membranes.
      Proteomic analyses reveal that the vesicles contain a broad array of
      macromolecules, many of which are associated with fungal virulence. Further, the
      biological import of the extracellular fungal vesicles is supported by their
      presence during murine cryptococcosis and the immunoreactivity of convalescent
      serum from patients with Cryptococcus neoformans or Histoplasma capsulatum
      vesicle protein extracts.In contrast to most eukaryotic cells, fungi have complex
      cell walls, that could in theory provide a significant barrier to the secretion
      of large molecules. The discovery of trans-cell wall vesicular transport in fungi
      provides a solution to the problem of extracellular transport of macromolecules.
      Identifying similar vesicles in ascomycetes and basidiomycetes suggest that the
      shuttle system is ancient, predating the divergence of these branches 0.5-1.0
      billion years ago. Importantly, the discovery of this trans-cell wall vesicular
      transport system also poses new, interesting questions for future investigations.

PMID- 19169362
TI  - Stress effects on working memory, explicit memory, and implicit memory for
      neutral and emotional stimuli in healthy men.
AB  - Stress is a strong modulator of memory function. However, memory is not a unitary
      process and stress seems to exert different effects depending on the memory type
      under study. Here, we explored the impact of social stress on different aspects
      of human memory, including tests for explicit memory and working memory (for
      neutral materials), as well as implicit memory (perceptual priming, contextual
      priming and classical conditioning for emotional stimuli). A total of 35 young
      adult male students were randomly assigned to either the stress or the control
      group, with stress being induced by the Trier Social Stress Test (TSST). Salivary
      cortisol levels were assessed repeatedly throughout the experiment to validate
      stress effects. The results support previous evidence indicating complex effects
      of stress on different types of memory: A pronounced working memory deficit was
      associated with exposure to stress. No performance differences between groups of
      stressed and unstressed subjects were observed in verbal explicit memory (but
      note that learning and recall took place within 1 h and immediately following
      stress) or in implicit memory for neutral stimuli. Stress enhanced classical
      conditioning for negative but not positive stimuli. In addition, stress improved
      spatial explicit memory. These results reinforce the view that acute stress can
      be highly disruptive for working memory processing. They provide new evidence for
      the facilitating effects of stress on implicit memory for negative emotional
      materials. Our findings are discussed with respect to their potential relevance
      for psychiatric disorders, such as post traumatic stress disorder.

PMID- 19169364
TI  - Multiple assessment in quality of life trials: how many questionnaires? How often
      should they be given?
AB  - Researchers conducting randomized trials of integrative interventions often ask
      patients to complete multiple different quality of life questionnaires or symptom
      severity scales repeatedly over the course of a trial. Although trialists rarely
      if ever give a strong justification for either the number of questionnaires they
      give or how often they give them, these are design decisions that can be taken
      systematically. Giving large numbers of questionnaires can improve the precision
      of trial results, and provide interesting secondary data, such as on the time
      course of symptoms. However, doing so can also lead to excessive patient drop
      out, an undue data management burden and difficulties with interpretation of
      results. As a general guideline, each aspect of quality of life should be
      measured by a single questionnaire, and researchers should avoid giving more than
      three different questionnaires to patients. Decisions about the appropriate
      number of assessments to use can be based on statistical properties derived from
      simple formulae.

PMID- 19169365
TI  - Single Case Evaluation of an Intensive Cognitive Behavioral Treatment for
      Generalized Social Anxiety Disorder.
AB  - The present study investigated the efficacy of an 8-day, 6-session, intensive
      individual cognitive behavioral therapy protocol for social anxiety disorder
      using a multiple baseline across subjects design with 1, 2, and 3 months follow
      up assessments. Participants were 5 outpatients with generalized social anxiety
      disorder. The intervention had variable effects on clinician-rated and self
      report measures of anxiety and depression. The results question the efficacy of
      intensive psychotherapy as a general therapeutic strategy for social anxiety
      disorder. Directions for future research are discussed.

PMID- 19169367
TI  - Ethnic Differences in Attributions and Treatment Expectancies for Adolescent
      Depression.
AB  - Studies suggest that ethnicity and socioeconomic factors may relate to
      differences in treatment expectancies and the attributions made for emotional or
      behavioral problems. We examined ethnic differences in (1) parents' attributions
      about the causes of adolescent behavioral and emotional problems and (2)
      treatment expectancies among 236 adolescent participants who enrolled in a 36
      week randomized controlled trial for depression. Controlling for education and
      income, European American parents were more likely to endorse beliefs reflecting
      physical causes of depression than African American parents. There were no ethnic
      differences for beliefs reflecting external, familial, or community factors.
      Ethnic differences were observed in the treatment expectancies reported by
      parents, but not adolescents, with African American parents more likely than
      European Americans and Other minorities to endorse positive expectations for CBT.
      These findings may have implications for understanding discrepancies in mental
      health service use.

PMID- 19169368
TI  - Electrolyte and Fluid Transport in Mesothelial Cells.
AB  - Mesothelial cells are specialized epithelial cells, which line the pleural,
      pericardial, and peritoneal cavities. Accumulating evidence suggests that the
      monolayer of mesothelial cells is permeable to electrolyte and fluid, and thereby
      govern both fluid secretion and re-absorption in the serosal cavities. Disorders
      in these salt and fluid transport systems may be fundamental in the pathogenesis
      of pleural effusion, pericardial effusion, and ascites. In this review, we
      discuss the location, physiological function, and regulation of active transport
      (Na(+)-K(+)-ATPase) systems, cation and anion channels (Na(+), K(+), Cl(-), and
      Ca(2+) channels), antiport (exchangers) systems, and symport (co-transporters)
      systems, and water channels (aquaporins). These secretive and absorptive pathways
      across mesothelial monolayer cells for electrolytes and fluid may provide pivotal
      therapeutical targets for novel clinical intervention in edematous diseases of
      serous cavities.

PMID- 19169369
TI  - The Influence of Varied Amide Bond Positions on Hydraphile Ion Channel Activity.
AB  - Hydraphile compounds have been prepared in which certain of the amine nitrogens
      have been replaced by amide residues. The amide bonds are present either in the
      sidearm, the side chain, or the central relay. Sodium cation transport through
      phospholipid vesicles mediated by each hydraphile was assessed. All of the amide
      containing hydraphiles showed increased levels of Na(+) transport compared to the
      parent compound, but the most dramatic rate increase was observed for sidearm
      amine to amide replacement. We attribute this enhancement to stabilization of the
      sidearm in the bilayer to achieve a better conformation for ion conduction.
      Biological studies of the amide hydraphiles with E. coli and B. subtilis showed
      significant toxicity only with the latter. Further, the consistency between the
      efficacies of ion transport and toxicity previously observed for non-amidic
      hydraphiles was not in evidence.

PMID- 19169370
TI  - Regulation of Hemostasis by the Sympathetic Nervous System: Any Contribution to
      Coronary Artery Disease?
AB  - Within the last two decades, hemostasis factors have emerged as 'new' risk
      factors for coronary artery disease. Historical studies on the physiology of the
      sympathetic nervous system (SNS) attributed accelerated blood clotting to the
      components of the fight-flight response. Although this has not been demonstrated,
      exaggerated clotting related to SNS hyperactivity might confer an increased
      arterial thrombotic risk. This review outlines the effects of sympathetic
      activation as mimicked by adrenergic infusions and as elicited by mental stress
      and physical exercise, and the molecular mechanisms involved. A selective review
      of the pertinent literature was undertaken. Sympathetic activation provokes a
      simultaneous increase in molecules of both the coagulation and fibrinolysis
      pathways within minutes, resulting in net hypercoagulability as a part of normal
      human physiology. Catecholamines and adrenergic receptors interact to mediate
      hemostatic changes. Exaggerated procoagulant changes in individuals with a
      preexistent atherosclerotic disease, in those experiencing ongoing stressful life
      circumstances and in the physically untrained might confer a thrombotic threat
      with sympathetic activation. Initial evidence suggests that nonselective beta
      adrenergic blockade may attenuate clotting acceleration upon SNS activation.
      Prospective studies are needed to demonstrate whether exaggerated clotting as
      elicited by the SNS is associated with an increased risk of cardiovascular
      morbidity and mortality. If confirmed, intervention studies targeted at reducing
      this risk, for example with drugs, psychotherapy (including stress management)
      and regular physical exercise, would be warranted.

PMID- 19169371
TI  - Representation of the Self in REM and NREM Dreams.
AB  - The authors hypothesized that representations of the Self (or the dreamer) in
      dreams would change systematically, from a prereflective form of Self to more
      complex forms, as a function of both age and sleep state (REM vs. non-REM). These
      hypotheses were partially confirmed. While the authors found that all the self
      concept-related dream content indexes derived from the Hall/Van de Castle dream
      content scoring system did not differ significantly between the dreams of
      children and adults, adult Selves were more likely to engage in "successful"
      social interactions. The Self never acted as aggressor in NREM dream states and
      was almost always the befriender in friendly interactions in NREM dreams.
      Conversely, the REM-related dream Self preferred aggressive encounters. Our
      results suggests that while prereflective forms of Self are the norm in
      children's dreams, two highly complex forms of Self emerge in REM and NREM
      dreams.

PMID- 19169372
TI  - Magnetoacoustic tomographic imaging of electrical impedance with magnetic
      induction.
AB  - Magnetoacoustic tomography with magnetic induction (MAT-MI) is a recently
      introduced method for imaging tissue electrical impedance properties by
      integrating magnetic induction and ultrasound measurements. In the present study,
      we have developed a focused cylindrical scanning mode MAT-MI system and the
      corresponding reconstruction algorithms. Using this system, we demonstrated 3
      dimensional MAT-MI imaging in a physical phantom, with cylindrical scanning
      combined with ultrasound focusing, and the ability of MAT-MI in imaging
      electrical conductivity properties of biological tissue.

PMID- 19169373
TI  - Anion Transport in Liposomes Responds to Variations in the Anchor Chains and the
      Fourth Amino Acid of Heptapeptide Ion Channels.
AB  - Seven heptapeptide derivatives have been prepared. The peptide structure is
      (Gly)(3)Xxx(Gly)(3) in which Xxx stands for a variable amino acid. The amino acid
      variations include azetidine carboxylic acid, pipecolic acid, meta-aminobenzoic
      acid, proline, and leucine. All seven compounds have a C-terminal benzyl group.
      In all cases, the heptapeptide's N-terminus was linked to diglycolic acid and a
      dialkylamine. In five cases, the N-terminal group was didecylamine and in two
      cases, N-ethyl-N-decyl. Chloride and carboxyfluorescein release from phospholipid
      vesicles was studied with the result that C(10)H(21)N(C(2)H(5)) COCH(2)OCH(2)CO
      NH-(Gly)(3)Leu(Gly)(3)-OCH(2)Ph was the most active. Hill analysis showed that
      this compound involves pore formation by four monomer units rather than two, as
      previously found for other members of this family.

PMID- 19169375
TI  - Coordination and transport of alkali metal cations through phospholipid bilayer
      membranes by hydraphile channels.
AB  - Hydraphiles are synthetic ionophores that were designed to mimic some properties
      of protein channels that conduct such cations as sodium. They use macrocyclic
      (crown) polyethers as amphiphilic headgroups and as entry and exit portals. Their
      overall length is controlled by covalent links between the two headgroups (distal
      macrocycles) and the "central relay" unit, typically also an azacrown. The
      hydraphiles insert in the bilayer membranes of synthetic phospholipid vesicles or
      vital cells and mediate the transport of cations. The hydraphiles were intended
      to be models but they are functional channels. Because they are symmetric, they
      are non-rectifying but they show open-close behavior characteristic of natural
      channels. Because they are non-rectifying, when they insert into a microbial
      membrane, they lead to a rapid change in osmotic balance that proves fatal to
      bacteria.

PMID- 19169374
TI  - Effects of Saccharide Spacing and Chain Extension on Toxin Inhibition by
      Glycopolypeptides of Well-Defined Architecture.
AB  - Many recognition events important in biology are mediated via multivalent
      interactions between relevant oligosaccharides and multiple saccharide receptors
      present on lectins, viruses, toxins, and cell surfaces. Because of the important
      role played by protein-carbohydrate interactions in these pathogenic recognition
      events and in other human diseases, considerable effort has been devoted toward
      the development of multivalent polymeric ligands for carbohydrate-binding
      proteins. In this work, we report the synthesis of new polypeptide-based
      glycopolymers produced via a combination of protein engineering and chemical
      methods. These methodologies permit control over the number and the spacing of
      saccharides on the scaffold, as well as the conformation of the polymer backbone,
      and allow a more purposeful design of polymers for manipulation of multivalent
      binding events. Two families of galactose-bearing glycopolypeptides with random
      coil conformations, [(AG)(3)PEG](y) (y = 10 and 16) and
      {[(AG)(2)PSG](2)[(AG)(2)PEG][(AG)(2)PSG](2)}(y) (y = 6), have been synthesized.
      The carboxylic acid functionality of the glutamic acid residues allowed
      subsequent modification with amino-saccharides to yield the desired
      glycopolypeptides; selective placement of the glutamic acid group permitted
      investigation of the effects of multivalency and saccharide spacing on toxin
      inhibition. In addition, a family of galactose-functionalized PGA-based
      glycopolymers of varying molecular weights was also synthesized to compare the
      effects of backbone flexibility and hydrodynamic volume, relative to the
      recombinant glycopolypeptides, on toxin inhibition. Glycopolypeptides were
      characterized via (1)H NMR, MALDI-TOF mass spectrometry, SDS-PAGE analysis, and
      spectrophotometric assays. They were tested as inhibitors of the binding of the
      cholera toxin B subunit via direct enzyme-linked assays. The data from these
      experiments confirm the relevance of appropriate saccharide spacing on
      controlling the binding event and also indicate the influence of chain extension
      in improving inhibition.

PMID- 19169376
TI  - Air-water interfacial behavior of amphiphilic peptide analogs of synthetic
      chloride ion transporters.
AB  - A family of heptapeptide-based chloride transporters (called synthetic anion
      transporters, SATs) were designed to insert into phospholipid membrane bilayers
      and form pores. Many of these compounds have proved to be chloride selective
      transporters. The transporters were designed to incorporate hydrophilic
      heptapeptides that could serves as headgroups and hydrocarbon tails that could
      serve as hydrophobic membrane anchors. Insertion of the SAT molecules into a
      bilayer requires approach to and insertion at the aqueous-membrane surface. The
      studies reported here were conducted to model and understand this process by
      studying SAT behavior at the air-water interface. A Langmuir trough was used to
      obtain surface pressure-area isotherm data. These data for amphiphilic SATs were
      augmented by Brewster angle microscopy (BAM), molecular modeling, and
      calculations of the hydrophobicity parameter log P. The analyses showed that the
      heptapeptide (hydrophilic) module of the SAT molecule rested on the water surface
      while the dialkyl (hydrophobic) tails oriented themselves in the air,
      perpendicular to the water surface. Brewster angle microscopy visually confirmed
      a high order of molecular organization. Results from these studies are consistent
      with the previously proposed mechanism of SAT membrane insertion and pore
      formation.

PMID- 19169377
TI  - New perspectives in clinical research: the Women's Cancer Research Foundation's
      experience.
AB  - The number of physicians involved in clinical research continues to decline.
      Financial and administrative barriers appear to be primarily responsible,
      although inadequate community-based infrastructure has also contributed
      significantly to this troubling phenomenon. Therefore, novel physician-friendly
      research models amenable to conducting efficient clinical research are necessary.
      The physicians from the Women's Cancer Research Foundation have developed such a
      paradigm over the past 23 years, which has proven to increase research
      productivity above and beyond the traditional academic model.

PMID- 19169379
TI  - "Anting" in Blue Jays: evidence in support of a food-preparatory function.
AB  - Anting, the plumage-dipping behavior to which ants (mostly formicines) are
      commonly subjected by birds (mostly passerines), is shown in tests with hand
      raised Blue Jays (Cyanocitta cristata) and the ant Formica exsectoides to be
      instinctive: the birds displayed typical renditions of the behavior on the first
      occasion that they encountered ants. Evidence is presented supportive of the view
      that anting is a strategy by which birds render ants fit for ingestion. Formicine
      ants are ordinarily protected by their formic acid-containing spray. Being wiped
      into the bird's plumage causes them to discharge that spray, without harm to the
      bird, to the point of almost total emptying of the glandular sac in which the
      secretion is stored. The ants are therefore essentially secretion-free by the
      time they are swallowed. Further evidence indicates that it is the ant's
      possession of the acid sac that triggers the anting behavior in the bird. If F.
      exsectoides are surgically deprived of their acid sac, they are eaten by the
      birds without first being subjected to anting. Data are also presented indicating
      that the ant's crop, which is especially capacious in formicines (its contents
      may amount to over 30% of the formicine's mass), and which appears to survive the
      anting procedure intact, constitutes, at least when laden, a valuable component
      of the trophic package that the bird accesses by anting.

PMID- 19169380
TI  - DETECTION OF ROAD HAZARDS BY NOVICE TEEN AND EXPERIENCED ADULT DRIVERS.
AB  - Previous laboratory and simulator research has indicated that hazard detection
      skills and abilities are less developed among novice drivers compared with
      experienced adult drivers. Novices tend to miss some relevant cues and may be
      less able to process important elements in the environment while driving. As was
      found with other research methods, it was hypothesized that novices would have
      lower hazard detection skills and will react less appropriately to hazards than
      older and more experienced drivers.Three hazard perception scenarios were
      simulated on a test track and data were collected on newly licensed teen drivers
      (within 2 weeks of licensure) and a comparison group of adults. The scenarios
      included a hidden stop sign, hidden pedestrian, and hidden pedestrian with lane
      closure (this last included a text-messaging task). Discrete quantitative
      performance metrics were evaluated for this analysis, including: 1) Did the
      participant glance at the potential hazard (e.g., stop sign, pedestrian)? 2) Did
      the participant stop (for the stop sign scenario)? 3) Did the participant show
      signs of indecision, caution, or awareness (for all hazards)?Significant
      differences between teen drivers and more experienced adult drivers were found in
      a combined hazard detection analysis. Results indicate that the adult drivers
      observed hazards and demonstrated overt recognition of hazards more frequently
      than the teen drivers. Results indicated that a large portion of teen drivers
      failed to disengage from peripheral task engagement in the presence of hazards.
      The results will later be compared to naturalistic data for the same set of
      drivers to see whether these test track results are predictive of real-world
      behavior.

PMID- 19169378
TI  - Elevated hydrostatic pressure triggers release of OPA1 and cytochrome C, and
      induces apoptotic cell death in differentiated RGC-5 cells.
AB  - PURPOSE: This study was conducted to determine whether elevated hydrostatic
      pressure alters mitochondrial structure, triggers release of the dynamin-related
      guanosine triphosphatase (GTPase) optic atrophy type 1 (OPA1) or cytochrome C
      from mitochondria, alters OPA1 gene expression, and can directly induce apoptotic
      cell death in cultured retinal ganglion cell (RGC)-5 cells. METHODS:
      Differentiated RGC-5 cells were exposed to 30 mmHg for three days in a
      pressurized incubator. As a control, differentiated RGC-5 cell cultures were
      incubated simultaneously in a conventional incubator. Live RGC-5 cells were then
      labeled with MitoTracker Red and mitochondrial morphology was assessed by
      fluorescence microscopy. Mitochondrial structural changes were also assessed by
      electron microscopy and three-dimensional (3D) electron microscope tomography.
      OPA1 mRNA was measured by Taqman quantitative PCR. The cellular distribution of
      OPA1 protein and cytochrome C was assessed by immunocytochemistry and western
      blot. Caspase-3 activation was examined by western blot. Apoptotic cell death was
      evaluated by the terminal deoxynucleotidyl transferase dUTP nick end labeling
      (TUNEL) method. RESULTS: Mitochondrial fission, characterized by the conversion
      of tubular fused mitochondria into isolated small organelles, was triggered after
      three days exposure to elevated hydrostatic pressure. Electron microscopy
      confirmed the fission and noted no changes to mitochondrial architecture, nor
      outer membrane rupture. Electron microscope tomography showed that elevated
      pressure depleted mitochondrial cristae content by fourfold. Elevated hydrostatic
      pressure increased OPA1 gene expression by 35+/-14% on day 2, but reduced
      expression by 36+/-4% on day 3. Total OPA1 protein content was not changed on day
      2 or 3. However, pressure treatment induced release of OPA1 and cytochrome C from
      mitochondria to the cytoplasm. Elevated pressure also activated caspase-3 and
      induced apoptotic cell death. CONCLUSIONS: Elevated hydrostatic pressure
      triggered mitochondrial changes including mitochondrial fission and abnormal
      cristae depletion, alteration of OPA1 gene expression, and release of OPA1 and
      cytochrome C into the cytoplasm before the onset of apoptotic cell death in
      differentiated RGC-5 cells. These results suggest that sustained moderate
      pressure elevation may directly damage RGC integrity by injuring mitochondria.

PMID- 19169381
TI  - Quantum Calculations On Hydrogen Bonds In Certain Water Clusters Show Cooperative
      Effects.
AB  - Water molecules in clefts and small clusters are in a significantly different
      environment than in bulk water. We have carried out ab initio calculations that
      demonstrate this in a series of clusters, showing that cooperative effects must
      be taken into account in the treatment of hydrogen bonds and water clusters in
      such bounded systems. Hydrogen bonds between water molecules in simulations are
      treated most frequently by using point charge water potentials, such as TIP3P or
      SPC, sometimes with a polarizable extension. These produce excellent results in
      bulk water, for which they are calibrated. Clefts are different from bulk; it is
      necessary to look at smaller systems, and investigate the effect of limited
      numbers of neighbors. We start with a study of isolated clusters of water with
      varying numbers of neighbors of a hydrogen bonded pair of water molecules. The
      cluster as a whole is in vacuum. The clusters are defined so as to provide the
      possible arrangements of nearest neighbors of a central hydrogen bonded pair of
      water molecules. We then scan the length and angles of the central hydrogen bond
      of the clusters, using density functional theory, for each possible arrangement
      of donor and acceptor hydrogen bonds on the central hydrogen bonding pair; the
      potential of interaction of two water molecules varies with the number of donor
      and of acceptor neighbors. This also involves changes in charge on the water
      molecules as a function of bond length, and changes in energy and length as a
      function of number of neighboring donor and acceptor molecules. Energy varies by
      approximately 6 k(B)T near room temperature from the highest to the lowest energy
      when bond length alone is varied, enough to seriously affect simulations.

PMID- 19169382
TI  - Patient and implanting physician factors associated with mortality and
      complications after implantable cardioverter-defibrillator implantation, 2002
      2005.
AB  - BACKGROUND: Little is known about factors that influence survival and
      complications after implantable cardioverter-defibrillator (ICD) implantation in
      routine clinical practice. We examined patient and implanting physician factors
      associated with outcomes of ICD therapy in Medicare beneficiaries from 2002
      through 2005. METHODS AND RESULTS: We limited this analysis to patients aged
      >or=65 with Medicare fee-for-service coverage who received an ICD between January
      2002 and September 2005. The main outcome measures are time to postprocedural
      complications within 90 days and 1-year mortality. During the study period, 8581
      patients had an ICD implanted by 1959 physicians. The number of procedures
      increased from 1644 in 2002 to 2374 in the first 3 quarters of 2005. The overall
      complication rate declined from 18.8% in 2002 to 14.2% in 2005 (P<0.001). Factors
      independently associated with an increased hazard of complications include
      chronic lung disease, dementia, renal disease, implantation by a thoracic
      surgeon, and implantation with removal/replacement. History of congestive heart
      failure, outpatient implantation, and more recent years of ICD implantation were
      associated with a lower risk of complications (P<0.05 for all factors). From 2002
      to 2005, we observed a decline in 1-year mortality (P<0.001). CONCLUSIONS: We
      observed an appreciable increase in the number of ICD implants, which was
      associated with a significant decrease in the rate of complications and 1-year
      mortality. We identified factors associated with an increased risk of mortality
      and postprocedural complications that may support more nuanced treatment
      decisions than are currently possible.

PMID- 19169383
TI  - Virtual Colonoscopy Screening with Ultra Low-Dose CT and Less-Stressful Bowel
      Preparation: A computer simulation study.
AB  - Computed tomography colonography (CTC) or CT-based virtual colonoscopy (VC) is an
      emerging tool for detection of colonic polyps. Compared to the conventional fiber
      optic colonoscopy, VC has demonstrated the potential to become a mass screening
      modality in terms of safety, cost, and patient compliance. However, current CTC
      delivers excessive X-ray radiation to the patient during data acquisition. The
      radiation is a major concern for screening application of CTC. In this work, we
      performed a simulation study to demonstrate a possible ultra low-dose CT
      technique for VC. The ultra low-dose abdominal CT images were simulated by adding
      noise to the sinograms of the patient CTC images acquired with normal dose scans
      at 100 mAs levels. The simulated noisy sinogram or projection data were first
      processed by a Karhunen-Loeve domain penalized weighted least-squares (KL-PWLS)
      restoration method and then reconstructed by a filtered backprojection algorithm
      for the ultra low-dose CT images. The patient-specific virtual colon lumen was
      constructed and navigated by a VC system after electronic colon cleansing of the
      orally-tagged residue stool and fluid. By the KL-PWLS noise reduction, the colon
      lumen can successfully be constructed and the colonic polyp can be detected in an
      ultra low-dose level below 50 mAs. Polyp detection can be found more easily by
      the KL-PWLS noise reduction compared to the results using the conventional noise
      filters, such as Hanning filter. These promising results indicate the feasibility
      of an ultra low-dose CTC pipeline for colon screening with less-stressful bowel
      preparation by fecal tagging with oral contrast.

PMID- 19169384
TI  - A Bayesian Framework for Estimating Vaccine Efficacy per Infectious Contact.
AB  - In vaccine studies for infectious diseases such as human immunodeficiency virus
      (HIV), the frequency and type of contacts between study participants and
      infectious sources are among the most informative risk factors, but are often not
      adequately adjusted for in standard analyses. Such adjustment can improve the
      assessment of vaccine efficacy as well as the assessment of risk factors. It can
      be attained by modeling transmission per contact with infectious sources.
      However, information about contacts that rely on self-reporting by study
      participants are subject to nontrivial measurement error in many studies. We
      develop a Bayesian hierarchical model fitted using Markov chain Monte Carlo
      (MCMC) sampling to estimate the vaccine efficacy controlled for exposure to
      infection, while adjusting for measurement error in contact-related factors. Our
      method is used to re-analyze two recent HIV vaccine studies, and the results are
      compared with the published primary analyses that used standard methods. The
      proposed method could also be used for other vaccines where contact information
      is collected, such as human papilloma virus vaccines.

PMID- 19169385
TI  - Direct Observation of Early-Time Hydrogelation in beta-Hairpin Peptide Self
      Assembly.
AB  - Triggered hydrogelation of MAX1 peptide, (VK)(4)-V(D)PPT-(KV)(4)-NH(2), proceeds
      through peptide intramolecular folding into beta-hairpins and concomitant self
      assembly into branched clusters of well-defined (uniform, 3 nm cross section),
      semiflexible, beta-sheet-rich nanofibrils. Cryogenic transmission electron
      microscopy indicates that dangling fibrils extend from one growing cluster to
      another and lead to early, intercluster communication in solution. At the
      apparent percolation threshold, the dynamic shear modulus measured by oscillatory
      rheology (G'(omega), G''(omega) proportional, variant omega(n)) and the field
      intensity autocorrelation function measured by dynamic light scattering
      (g(1)(tau) proportional, variant tau(-beta')) show power-law behavior with
      comparable critical dynamic exponents (n approximately 0.47 and beta'
      approximately 0.45). Finite interpenetration of percolating clusters with smaller
      clusters, along with permanent intercluster entanglements, increase the network
      rigidity. The self-assembly of MAX1 peptide was compared and contrasted with the
      assembly of other biopolymeric networks in literature.

PMID- 19169387
TI  - Adaptive and Effortful Control and Academic Self-efficacy Beliefs on Achievement:
      A Longitudinal Study of 1 through 3 Graders.
AB  - The linkages between self-regulatory processes and achievement were examined
      across three years in 733 children beginning at 1(st) grade (M = 6.57 years, SD =
      .39 at 1(st) grade) who were identified as lower achieving in literacy.
      Accounting for consistencies in measures (from one year prior) and for influences
      of child's age, gender, IQ, ethnicity and economic adversity on achievement,
      results indicate that adaptive/effortful control at 1(st) grade contributed to
      both academic self-efficacy beliefs at 2(nd) grade, and reading (but not math)
      achievement at 3(rd) grade. Although academic self-efficacy did not partially
      mediate the linkage between adaptive/effortful control and achievement, academic
      self-efficacy beliefs were positively correlated with reading and math. Results
      support the notion that early efforts to promote children's self-regulatory
      skills would enhance future academic self-beliefs and achievement, particularly
      in literacy.

PMID- 19169386
TI  - Mimicking the Self-Organized Microstructure of Tooth Enamel.
AB  - Under near-physiological pH, temperature, and ionic strength, amelogenin (Amel)
      accelerates hydroxyapatite (HAP) nucleation kinetics, decreasing the induction
      time in a concentration-dependent manner. Hierarchically organized apatite
      microstructures are achieved by self-assembly involving nucleated
      nanocrystallites and Amel oligomers and nanospheres at low supersaturations and
      protein concentrations in a slow and well-controlled constant composition (CC)
      system. The CC method allows the capture of an intermediate structure, the
      nanorod, following the formation of the critical nuclei at the earliest
      nucleation stages of calcium phosphate crystallization. The nanorod building
      blocks form spontaneously by synergistic interactions between flexible Amel
      protein assemblies and rigid calcium phosphate nanocrystallites. These
      intermediate structures further assemble by a self-epitaxial growth mechanism to
      form the final hierarchically organized microstructures that are compositionally
      and morphologically similar to natural enamel. This in vitro observation provides
      direct evidence that Amel promotes apatite crystallization and organization. We
      interpret our observations to propose that in vivo Amel may maximally exert an
      influence on the structural control of developing enamel crystals at the earliest
      nucleation stages.

PMID- 19169388
TI  - Theory and Inference for Regression Models with Missing Responses and Covariates.
AB  - In this paper, we carry out an in-depth theoretical investigation for inference
      with missing response and covariate data for general regression models. We assume
      that the missing data are Missing at Random (MAR) or Missing Completely at Random
      (MCAR) throughout. Previous theoretical investigations in the literature have
      focused only on missing covariates or missing responses, but not both. Here, we
      consider theoretical properties of the estimates under three different estimation
      settings: complete case analysis (CC), a complete response analysis (CR) that
      involves an analysis of those subjects with only completely observed responses,
      and the all case analysis (AC), which is an analysis based on all of the cases.
      Under each scenario, we derive general expressions for the likelihood and devise
      estimation schemes based on the EM algorithm. We carry out a theoretical
      investigation of the three estimation methods in the normal linear model and
      analytically characterize the loss of information for each method, as well as
      derive and compare the asymptotic variances for each method assuming the missing
      data are MAR or MCAR. In addition, a theoretical investigation of bias for the CC
      method is also carried out. A simulation study and real dataset are given to
      illustrate the methodology.

PMID- 19169389
TI  - Appropriateness of sling immobilization to prevent lead displacement after
      pacemaker/implantable cardioverter-defibrillator implantation.
AB  - After pacemaker/implantable cardioverter-defibrillator (pacemaker/ICD)
      implantation, patients are often required to immobilize the affected arm with a
      sling to minimize the risk of lead displacement. We examined whether performing a
      resistive range-of-motion exercise protocol after pacemaker/ICD surgery would
      result in lead displacement and, therefore, whether sling immobilization and
      activity restrictions are justified. Ten subjects who had undergone pacemaker/ICD
      surgery performed four individual resistive range-of-motion exercises (three sets
      of 10 repetitions for each: one warm-up set without weight and two sets with a 1-
      or 2-pound hand weight) with the affected arm prior to hospital discharge. For
      each subject, an electrophysiology nurse specialist used a noninvasive device
      programmer to evaluate surgical lead placement before and after the exercises. As
      an adjunct to the study, we queried clinicians at 48 US hospitals about sling
      immobilization and activity restrictions after pacemaker/ICD implantation at
      their institutions. No lead displacement occurred after the weightlifting
      exercises were performed. Based on these results in a small group of patients, it
      appears that requiring the use of a joint immobilization sling is overly
      restrictive, promotes fear, and hinders recovery. We encourage the development of
      consistent discharge instructions that will promote early mobility and a safe and
      rapid return to normal activities.

PMID- 19169390
TI  - Routine femoral head fluoroscopy to reduce complications in coronary
      catheterization.
AB  - We tested whether routine preprocedure fluoroscopy of the femoral head would
      improve sheath placement or reduce the incidence of groin complications. Patients
      were randomized to receive either fluoroscopy or "blind" sheath placement using
      palpation alone. The location of the femoral sheath was established by femoral
      artery angiography. Sheath placement in relation to the femoral head, arterial
      location, and complication rates were compared. Placement was considered "ideal"
      if the sheath was in the common femoral artery and in the top or middle third of
      the femoral head. A total of 256 patients were enrolled. There was no difference
      in average age, body mass index (BMI), or rate of anticoagulation between the
      groups. There was no major bleeding in either group. The overall risk of minor
      bleeding was not statistically different. The treatment group showed higher
      "ideal" placement relative to the femoral head. In patients who had a BMI >=30
      kg/m(2), the difference between the groups was statistically significant
      (treatment 69% vs control 50%). In conclusion, routine femoral fluoroscopy prior
      to sheath placement in coronary angiography and angioplasty did not significantly
      alter bleeding or complication rates but did increase the likelihood of ideal
      placement, especially in obese patients.

PMID- 19169391
TI  - Postsplenectomy reactive thrombocytosis.
AB  - Thrombocytosis is frequently encountered as an incidental laboratory finding. The
      most common etiology is reactive (secondary) thrombocytosis due to infections,
      trauma, surgery, or occult malignancy. Even though thrombocytosis is benign and
      self-limiting in most cases, it can result in hemorrhage or thrombosis. The
      hypercoagulable state is characterized by episodes of thrombosis and can be due
      to inherited or acquired conditions. Extreme thrombocytosis may result in
      thrombotic events such as acute myocardial infarction, mesenteric vein
      thrombosis, and pulmonary embolism. It is important for physicians to be familiar
      with the complications associated with thrombocytosis. Postsplenectomy reactive
      thrombocytosis has an incidence of about 75% to 82%. Thrombosis in association
      with elevated platelet count after splenectomy is well recognized, with an
      incidence of approximately 5%. This case report describes a 61-year-old patient
      who underwent emergent splenectomy and presented 1 week later with acute ST
      segment elevation myocardial infarction. Severe thrombocytosis, which was not
      present prior to splenectomy, was noted, and a diagnosis of reactive
      thrombocytosis was initially made. Involvement of the right coronary artery led
      to emergent percutaneous transluminal coronary angioplasty. Essential
      thrombocytosis was considered when treatment with hydroxyurea failed to lower the
      platelet count. A review of arterial and venous thrombosis in patients with
      severe thrombocytosis is presented, and the approach to the management of such
      patients is discussed.

PMID- 19169392
TI  - Cystic fibrosis diagnosed at age 45 based on symptoms of acute pancreatitis.

PMID- 19169393
TI  - Cardiac rehabilitation of a 77-year-old male runner: consideration of the
      athlete, not the age.
AB  - A 77-year-old geologist with coronary artery disease enrolled in our cardiac
      rehabilitation program after successful placement of a drug-eluting stent. Unlike
      the typical sedentary cardiac patient in his age group, he loved to run. He
      expressed a strong desire to return to his sport, and completion of a self
      assessment scale confirmed his high level of athletic identity. Despite the
      patient's advanced age and long history of unstable blood pressure, we were able
      to design a special exercise program that enabled him to train safely and thereby
      reach his goal. When developing a cardiac rehabilitation plan, health care
      professionals should consider the patient's athletic identity, not just his or
      her chronological age.

PMID- 19169394
TI  - Disseminated toxoplasmosis in a patient with undiagnosed AIDS.
AB  - Approximately 60% of deaths in patients with AIDS are a direct result of
      infection other than HIV. The more severe and life-threatening complications of
      HIV infection occur in patients with a CD4(+) T cell count <200 cells/MUL. In the
      absence of effective retroviral therapy, these infections are associated with a
      high mortality. We describe a case of disseminated toxoplasmosis discovered at
      autopsy in a patient with undiagnosed AIDS.

PMID- 19169396
TI  - The donor project.

PMID- 19169395
TI  - A flight emergency.

PMID- 19169397
TI  - Dr. Joseph Warren: leader in medicine, politics, and revolution.

PMID- 19169398
TI  - Carolyn Michelle Matthews, MD: a conversation with the editor.

PMID- 19169399
TI  - Barry Wayne Uhr, MD: a conversation with the editor.

PMID- 19169400
TI  - Free data with a price.

PMID- 19169401
TI  - To be boarded or not to be boarded?

PMID- 19169402
TI  - Saving lives: a letter from a young physician.

PMID- 19169403
TI  - Management of HIV-1 infection in adults.

PMID- 19169405
TI  - HIV-associated lymphoma.

PMID- 19169404
TI  - Creutzfeldt-Jakob disease: case discussion and imaging review.

PMID- 19169406
TI  - Primary effusion lymphoma diagnosed by pericardiocentesis.
AB  - Primary effusion lymphoma (PEL), formerly known as body cavity-based lymphoma, is
      a high-grade B-cell non-Hodgkin's lymphoma associated with Kaposi's sarcoma and
      human herpesvirus 8 infection. It usually affects serous body cavities and
      results in recurrent lymphomatous effusions. PEL is often diagnosed in patients
      with HIV infection and carries a poor prognosis, with median survival near 6
      months. We describe a patient who presented with symptomatic pericardial
      effusion, secondary to newly diagnosed PEL, and no prior history of HIV
      infection.

PMID- 19169407
TI  - Global T-wave inversion in a 77-year-old woman.

PMID- 19169408
TI  - Getting stiffed no longer needs to be a cost of doing business: Texas prompt pay
      provisions.

PMID- 19169409
TI  - Facts and ideas from anywhere.

PMID- 19169410
TI  - Dual transneuronal tracing in the rat entorhinal-hippocampal circuit by
      intracerebral injection of recombinant rabies virus vectors.
AB  - Dual transneuronal tracing is a novel viral tracing methodology which employs two
      recombinant viruses, each expressing a different reporter protein. Peripheral
      injection of recombinant pseudorabies viruses has been used as a powerful method
      to define neurons that coordinate outputs to various peripheral targets of motor
      and autonomic systems. Here, we assessed the feasibility of recombinants of
      rabies virus (RV) vector for dual transneuronal tracing in the central nervous
      system. First, we examined whether two different RV-vectors can double label
      cells in vitro, and showed that efficient double labeling can be realized by
      infecting targeted cells with the two RV-vectors within a short time interval.
      The potential of dual transneuronal tracing was then examined in vivo in the
      entorhinal-hippocampal circuit, using the chain of projections from CA3 pyramidal
      cells to CA1 pyramidal cells and subsequently to entorhinal cortex. Six days
      after the injection of two RV-vectors into the left and right entorhinal cortex
      respectively, double-labeled neurons were observed in CA3 bilaterally. Some
      double-labeled neurons showed a Golgi-like labeling. Dual transneuronal tracing
      potentially provides a powerful and sensitive method to study issues such as the
      amount of convergence and divergence within and between circuits in the central
      nervous system. Using this sensitive technique, we established that single
      neurons in CA3 are connected to the entorhinal cortex bilaterally with only one
      synaptic relay.

PMID- 19169411
TI  - Common variation in the SERPING1 gene is not associated with age-related macular
      degeneration in two independent groups of subjects.
AB  - PURPOSE: Common genetic variation in the complement component 1 inhibitor gene
      (SERPING1) was recently reported to increase the risk of developing age-related
      macular degeneration (AMD). This study was performed to replicate the association
      between SERPING1 and AMD. METHODS: Seven single nucleotide polymorphisms (SNPs)
      tagging common haplotypes across SERPING1 were genotyped on 786 (The Mayo Clinic)
      subjects and the association with AMD studied using single SNP and haplotype
      association analyses. The SNP in intron 6 (rs2511989) previously reported to
      increase the risk of AMD was studied in an additional 1,541 subjects from the Age
      Related Eye Disease Study (AREDS). Association with specific subtypes of AMD and
      interaction with four other loci: complement factor H (CFH), age-related
      maculopathy susceptibility 2 (ARMS2/LOC387715), High Temperature Requirement
      Factor A1 (HTRA1), complement factor B/complement component 2 (CFB/C2), and
      complement component 3 (C3) involved in AMD was explored. RESULTS: The seven tag
      SNPs were not associated with AMD in the Mayo subjects (p=0.13-0.70) and
      rs2511989 was also not associated with AMD in the Mayo or AREDS subjects (p=0.44
      0.45). Evaluation of haplotypes across SERPING1 did not reveal association with
      AMD (p=0.14-0.97). SNPs were not associated with AMD subtypes (early, geographic
      atrophy, or exudation). No interaction with other AMD risk variants was observed.
      CONCLUSIONS: We were unable to replicate the reported association between
      SERPING1 and AMD in two independent groups of subjects.

PMID- 19169412
TI  - Evaluation of MFRP as a candidate gene for high hyperopia.
AB  - PURPOSE: Mutations in the membrane-type frizzled-related protein (MFRP) gene have
      been identified in patients with pathologic high hyperopia associated with
      nanophthalmos or microphthalmia. This study is to test if a mutation in MFRP is
      responsible for physiologic high hyperopia. METHODS: DNA was prepared from venous
      leukocytes of 51 patients with physiologic high hyperopia (refraction of
      spherical equivalent > or = +5.00 [diopters] D) and 96 controls (refraction of
      spherical equivalent between -0.50 D and +1.00 D). The coding regions and
      adjacent intronic sequence of MFRP were amplified by polymerase chain reaction
      (PCR) and were then analyzed by cycle sequencing. Variations detected were
      further evaluated in normal controls and available family members by heteroduplex
      single-strand conformation polymorphism (SSCP) analysis or sequencing. RESULTS:
      The average spherical refractive error of patients was +8.41 D in the right eye
      (from +6.00 D to +16.5 D) and was +8.76 D in the left eye (from +6.00 D to +16.5
      D). Five novel heterozygous variations in MFRP, c.55-14_55-13insGTAT, c.496C>G,
      c.664C>A, c.669G>A, and c.770G>A, were identified. Of these, c.664C>A
      (p.Pro222Thr) and c.669G>A (p.=) were not observed in the 96 normal controls. In
      addition, one known c.192C>G substitution and five single nucleotide
      polymorphisms (SNPs; rs883247, rs3814762, rs36015759, rs2510143, and rs35885438)
      were detected. CONCLUSIONS: Several novel variations in MFRP were detected in
      Chinese. Our results imply that MFRP is less likely to play a major role in
      physiologic high hyperopia.

PMID- 19169413
TI  - Generation of immature retinal neurons from proliferating cells in the pars plana
      after retinal histogenesis in mice with retinal degeneration.
AB  - PURPOSE: To study the differentiation of immature retinal neurons/retinal
      precursors in the ciliary epithelium after retinal histogenesis in mice with
      inherited or acquired retinal degeneration. METHODS: Immunoreactivity to anti
      recoverin, rhodopsin, and Pax6 antibodies and binding to peanut agglutinin were
      analyzed histologically. The distribution and differentiation of immature retinal
      neurons/retinal precursors in the ciliary epithelium of mice with inherited
      (C3H/HeJ) and acquired (C57BL mice injected with 60 mg/kg N-methyl-N-nitrosourea)
      retinal degeneration were assessed. Proliferating retinal progenitors were
      labeled with bromodeoxyuridine (BrdU), and they were studied histologically using
      retinal markers. RESULTS: Many cells of rod and cone photoreceptor lineage were
      identified within the ciliary epithelium of the pars plana in adult mice with
      inherited retinal degeneration. Tracking experiments using BrdU indicated that
      some of recoverin-positive cells in the pars plana (approximately 3%) were
      generated after retinal histogenesis, and few were produced at or after postnatal
      day 24 (P24). The induction of acquired retinal degeneration in adult wild-type
      mice (P30) increased the number of BrdU-positve cells by roughly fourfold and
      recoverin-positive cells by approximately 17-fold in the pars plana. Moreover,
      some (approximately 1.5%) of the recoverin-positive cells were newly generated
      from dividing retinal progenitors in the adult pars plana. CONCLUSIONS: In
      response to retinal damage, an increased number of immature retinal
      neurons/retinal precursors was observed in the pars plana of mice with acquired
      and inherited retinal degeneration. Some of these cells differentiated from
      proliferating cells even after retinal histogenesis.

PMID- 19169414
TI  - Localization of the brainstem GABAergic neurons controlling paradoxical (REM)
      sleep.
AB  - Paradoxical sleep (PS) is a state characterized by cortical activation, rapid eye
      movements and muscle atonia. Fifty years after its discovery, the neuronal
      network responsible for the genesis of PS has been only partially identified. We
      recently proposed that GABAergic neurons would have a pivotal role in that
      network. To localize these GABAergic neurons, we combined immunohistochemical
      detection of Fos with non-radioactive in situ hybridization of GAD67 mRNA (GABA
      synthesis enzyme) in control rats, rats deprived of PS for 72 h and rats allowed
      to recover after such deprivation. Here we show that GABAergic neurons gating PS
      (PS-off neurons) are principally located in the ventrolateral periaqueductal gray
      (vlPAG) and the dorsal part of the deep mesencephalic reticular nucleus
      immediately ventral to it (dDpMe). Furthermore, iontophoretic application of
      muscimol for 20 min in this area in head-restrained rats induced a strong and
      significant increase in PS quantities compared to saline. In addition, we found a
      large number of GABAergic PS-on neurons in the vlPAG/dDPMe region and the
      medullary reticular nuclei known to generate muscle atonia during PS. Finally, we
      showed that PS-on neurons triggering PS localized in the SLD are not GABAergic.
      Altogether, our results indicate that multiple populations of PS-on GABAergic
      neurons are distributed in the brainstem while only one population of PS-off
      GABAergic neurons localized in the vlPAG/dDpMe region exist. From these results,
      we propose a revised model for PS control in which GABAergic PS-on and PS-off
      neurons localized in the vlPAG/dDPMe region play leading roles.

PMID- 19169415
TI  - Co-registration of In-Vivo Human MRI Brain Images to Postmortem Histological
      Microscopic Images.
AB  - Certain features such as small vascular lesions seen in human MRI are detected
      reliably only in postmortem histological samples by microscopic imaging. Co
      registration of these microscopically detected features to their corresponding
      locations in the in-vivo images would be of great benefit to understanding the
      MRI signatures of specific diseases. Using non-linear Polynomial transformation,
      we report a method to co-register in-vivo MRIs to microscopic images of
      histological samples drawn off the postmortem brain. The approach utilizes
      digital photographs of postmortem slices as an intermediate reference to co
      register the MRIs to microscopy. The overall procedure is challenging due to
      gross structural deformations in the postmortem brain during extraction and
      subsequent distortions in the histological preparations. Hemispheres of the brain
      were co-registered separately to mitigate these effects. Approaches relying on
      matching single-slices, multiple-slices and entire volumes in conjunction with
      different similarity measures suggested that using four slices at a time in
      combination with two sequential measures, Pearson correlation coefficient
      followed by mutual information, produced the best MRI-postmortem co-registration
      according to a voxel mismatch count. The accuracy of the overall registration was
      evaluated by measuring the 3D Euclidean distance between the locations of
      microscopically identified lesions on postmortem slices and their MRI-postmortem
      co-registered locations. The results show a mean 3D displacement of 5.1 +/- 2.0
      mm between the in-vivo MRI and microscopically determined locations for 21
      vascular lesions in 11 subjects.

PMID- 19169416
TI  - High Dimensional Classification Using Features Annealed Independence Rules.
AB  - Classification using high-dimensional features arises frequently in many
      contemporary statistical studies such as tumor classification using microarray or
      other high-throughput data. The impact of dimensionality on classifications is
      largely poorly understood. In a seminal paper, Bickel and Levina (2004) show that
      the Fisher discriminant performs poorly due to diverging spectra and they propose
      to use the independence rule to overcome the problem. We first demonstrate that
      even for the independence classification rule, classification using all the
      features can be as bad as the random guessing due to noise accumulation in
      estimating population centroids in high-dimensional feature space. In fact, we
      demonstrate further that almost all linear discriminants can perform as bad as
      the random guessing. Thus, it is paramountly important to select a subset of
      important features for high-dimensional classification, resulting in Features
      Annealed Independence Rules (FAIR). The conditions under which all the important
      features can be selected by the two-sample t-statistic are established. The
      choice of the optimal number of features, or equivalently, the threshold value of
      the test statistics are proposed based on an upper bound of the classification
      error. Simulation studies and real data analysis support our theoretical results
      and demonstrate convincingly the advantage of our new classification procedure.

PMID- 19169417
TI  - Evaluation of Patient Navigation in a Community Radiation Oncology Center
      Involved in Disparities Studies: A Time-to-Completion-of-Treatment Study.
AB  - PURPOSE: To evaluate whether data on length of time from patient referral to
      treatment completion, collected routinely as part of a quality improvement
      program, can be used to measure the effectiveness of a patient navigator program.
      PATIENTS AND METHODS: During a calendar year, 72 disparities patients, 38 of whom
      received navigator services, and a group of 157 nondisparate, un-navigated
      patients received external beam radiation therapy at a community center. Data
      from referral time through completion of treatment, which had been collected
      routinely under an existing continuous quality improvement program, were compared
      retrospectively, as well as missed treatments and the percentage of planned
      treatments completed, for three patient groups. RESULTS: The average number of
      days from referral to consult and from consult to start of treatment were lower
      for the navigated disparate group (6.66 and 14.56 days, respectively) than un
      navigated groups (disparate: 7.37 and 15.97 days; non-disparate: 8.97 and 16.24
      days, respectively). The percentage of patients completing treatment was lower
      for the navigated group (85%) than the un-navigated groups (95% and 97%), despite
      equivalent treatment percentage completion rates for all groups (97.0% to 98.8%).
      The navigated group missed more treatment days (1.86 days/patient) than the un
      navigated disparate group (0.47 days/patient) or the non-disparate group (0.83
      days/patient.) CONCLUSION: Some statistically insignificant differences were
      noted in favor of patient navigation (PN) but the significance is unclear because
      of the large data spread and the small numbers of patients. Given that the study
      was retrospective, it is also unclear whether these differences were influenced
      by the patient navigator. Repeat studies using the same data elements will
      provide a better platform for assessing whether such data can provide a measure
      of the effectiveness of PN in the radiation oncology setting. Given that the
      patients were not observed routinely by the navigator after the start of
      treatment unless a particular barrier was identified, there is an opportunity to
      assess whether interventions by the navigator could improve treatment completion
      rates and reduce the number of missed treatments.

PMID- 19169418
TI  - Height, health, and inequality: the distribution of adult heights in India.

PMID- 19169419
TI  - Dipole Parallel-Alignment in the Crystal Structure of a Polar Biphenyl: 4'-Acetyl
      4-Methoxybiphenyl (AMB).
AB  - 4'-Acetyl-4-methoxy-biphenyl (AMB) was synthesized via catalytic Suzuki cross
      coupling reaction and the crystal structure was determined. The crystals of AMB
      feature an orthorhombic unit cell with a = 7.900(6) A, b = 5.429(4) A, and c =
      26.80(2) A and the crystals are noncentrosymmetric, space group Pna2(1). The
      crystal structure of AMB features parallel-alignment of essentially planar
      molecules in the syn-conformation with molecular dipole moments of about 5.4
      Debye and affords about 53% of maximal polar alignment. The polar crystal
      structure of syn-AMB contrasts with the nonpolar crystal structure of the
      homologue 4-methoxyacetophenone syn-MAP. The fundamental difference between the
      packing motives of AMB and MAP is explained on the basis of lateral arene-arene
      interactions. The lattice architecture of AMB is compared to the motives realized
      in the only two other parallel-aligned polar biphenyls, 4'-n-butoxy-4
      cyanobiphenyl (nBCB) and 4'-dimethylamino-4-cyanobiphenyl (DMACB). The analysis
      provides conceptual insights to guide the rational design of polar materials and
      several resulting hypotheses are stated explicitly and can be tested.

PMID- 19169420
TI  - Emotion, Affect, and Risk Communication with Older Adults: Challenges and
      Opportunities.
AB  - Recent research suggests that emotion, affect, and cognition play important roles
      in risk perception and that their roles in judgment and decision-making processes
      may change over the lifespan. This paper discusses how emotion and affect might
      help or hinder risk communication with older adults. Currently, there are few
      guidelines for developing effective risk messages for the world's aging
      population, despite the array of complex risk decisions that come with increasing
      age and the importance of maintaining good decision making in later life. Age
      related declines in cognitive abilities such as memory and processing speed,
      increased reliance on automatic processes, and adaptive motivational shifts
      toward focusing more on affective (especially positive) information mean that
      older and younger adults may respond differently to risk messages. Implications
      for specific risk information formats (probabilities, frequencies, visual
      displays, and narratives) are discussed and directions for future research are
      highlighted.

PMID- 19169421
TI  - A New Approach to Fabricating High-density Nanoarrays by Nanocontact Printing.
AB  - We introduce a new scheme of nanocontact printing that fabricates nanoarrays
      using stamps generated by ultraviolet nanoimprint lithography. Array patterns can
      be generated by this printing technique in a high-density (number of features per
      unit area) fashion with a feature size as low as 30 nm and period of 100 nm. Sub
      500 nm alignment accuracy for multilayer printing has been obtained using a
      traditional contact mask aligner. We also demonstrate that we can image a
      nanoarray labeled by streptavidin by atomic force microscope (AFM).

PMID- 19169422
TI  - A Robust Algorithm for Point Set Registration Using Mixture of Gaussians.
AB  - This paper proposes a novel and robust approach to the point set registration
      problem in the presence of large amounts of noise and outliers. Each of the point
      sets is represented by a mixture of Gaussians and the point set registration is
      treated as a problem of aligning the two mixtures. We derive a closed-form
      expression for the L(2) distance between two Gaussian mixtures, which in turn
      leads to a computationally efficient registration algorithm. This new algorithm
      has an intuitive interpretation, is simple to implement and exhibits inherent
      statistical robustness. Experimental results indicate that our algorithm achieves
      very good performance in terms of both robustness and accuracy.

PMID- 19169423
TI  - ENHANCEMENT OF CELL BOUNDARIES IN TRANSMISSION ELECTRON MICROSCOPY IMAGES.
AB  - Transmission electron microscopy (TEM) is an important modality for the analysis
      of cellular structures in neurobiology. The computational analysis of neurons
      entail their segmentation and reconstruction from TEM images. This problem is
      complicated by the heavily textured nature of cellular TEM images and typically
      low signal-to-noise ratios. In this paper, we propose a new partial differential
      equation for enhancing the contrast and continuity of cell membranes in TEM
      images.

PMID- 19169424
TI  - Using Wavelet-Based Functional Mixed Models to Characterize Population
      Heterogeneity in Accelerometer Profiles: A Case Study.
AB  - We present a case study illustrating the challenges of analyzing accelerometer
      data taken from a sample of children participating in an intervention study
      designed to increase physical activity. An accelerometer is a small device worn
      on the hip that records the minute-by-minute activity levels of the child
      throughout the day for each day it is worn. The resulting data are irregular
      functions characterized by many peaks representing short bursts of intense
      activity. We model these data using the wavelet-based functional mixed model.
      This approach incorporates multiple fixed effect and random effect functions of
      arbitrary form, the estimates of which are adaptively regularized using wavelet
      shrinkage. The method yields posterior samples for all functional quantities of
      the model, which can be used to perform various types of Bayesian inference and
      prediction. In our case study, a high proportion of the daily activity profiles
      are incomplete, i.e. have some portion of the profile missing, so cannot be
      directly modeled using the previously described method. We present a new method
      for stochastically imputing the missing data that allows us to incorporate these
      incomplete profiles in our analysis. Our approach borrows strength from both the
      observed measurements within the incomplete profiles and from other profiles,
      from the same child as well as other children with similar covariate levels,
      while appropriately propagating the uncertainty of the imputation throughout all
      subsequent inference. We apply this method to our case study, revealing some
      interesting insights into children's activity patterns. We point out some
      strengths and limitations of using this approach to analyze accelerometer data.

PMID- 19169425
TI  - Addressing Absence.

PMID- 19169426
TI  - Metachronal wave formation in a model of pulmonary cilia.
AB  - A three-dimensional simulation of the formation of metachronal waves in rows of
      pulmonary cilia is presented. The cilia move in a two-layer fluid model. The
      fluid layer adjacent to the cilia bases is purely viscous while the tips of the
      cilia move through a viscoelastic fluid. An overlapping fixed-moving grid
      formulation is employed to capture the effect of the cilia on the surrounding
      fluid. In contrast with immersed boundary methods, this technique allows a
      natural enforcement of boundary conditions without the need for smoothing of
      singular force distributions. The fluid domains are discretized using a finite
      volume method. The 9 + 2 internal microtubule structure of an individual cilium
      is modeled using large-deflection, curved, finite-element beams. The microtubule
      skeleton is cross-linked to itself and to the cilium membrane through spring
      elements which model nexin links. The cilium membrane itself is considered to be
      elastic and subject to fluid stresses computed from the moving grid formulation
      as well as internal forces transmitted from the microtubule skeleton. A cilium is
      set into motion by the action of dynein molecules exerting forces between
      adjacent microtubules. Realistic models of the forces exerted by dynein molecules
      are extracted from measurements of observed cilia shapes.

PMID- 19169427
TI  - An Evaluation of Iterative Reconstruction Strategies on Mediastinal Lesion
      Detection Using Hybrid Ga-67 SPECT Images.
AB  - Hybrid LROC studies can be used to more realistically assess the impact of
      reconstruction strategies, compared to those constructed with digital phantoms.
      This is because hybrid data provides the background variability that is present
      in clinical imaging, as well as, control over critical imaging parameters,
      required to conduct meaningful tests. Hybrid data is obtained by adding Monte
      Carlo simulated lesions to disease free clinical projection data. Due to Ga-67
      being a particularly challenging radionuclide for imaging, we use Ga-67 hybrid
      SPECT data to study the effectiveness of the various correction strategies
      developed to account for degradations in SPECT imaging. Our data was obtained
      using GE-VG dual detector SPECT-CT camera. After determining a target lesion
      contrast we conduct pilot LROC studies to obtain a near-optimal set of
      reconstruction parameters for the different strategies individually. These near
      optimal parameters are then used to reconstruct the final evaluation study sets.
      All LROC study results reported here were obtained employing human observers
      only. We use final LROC study results to assess the impact of attenuation
      compensation, scatter compensation and detector resolution compensation on data
      reconstructed with the RBI-EM algorithm. We also compare these with FBP
      reconstructions of the same dataset. Our experiment indicates an improvement in
      detection accuracy, as various degradations inherent in the image acquisition
      process are compensated for in the reconstruction process.

PMID- 19169428
TI  - Factors Influencing Lesion Detection in SPECT Lung Images.
AB  - An earlier localization ROC (LROC) study that found attenuation correction (AC)
      degraded the detection of solitary pulmonary nodules (SPN) in hybrid SPECT lung
      images had several potential shortcomings related to the simulation methods. We
      sought to address these issues with a revised LROC study. Clinical Tc-99m NeoTect
      scans acquired with a simultaneous transmission-emission protocol defined the
      normal cases in a single-slice LROC study. Abnormal cases contained a simulated 1
      cm lung lesion. Four rescaled-block-iterative EM (RBI) reconstruction strategies
      applied: 1) AC, scatter correction (SC), and resolution compensation (RC); 2) AC
      only; 3) RC only; and 4) no corrections (NC). Images from these strategies
      underwent 3D Gaussian post-smoothing. Performances were defined by the average
      area under the LROC curve obtained from three human observers. The strategy
      ranking in order of decreasing performance was: 1) RBI with RC; 2) RBI with all
      corrections; 3) RBI with AC; and 4) RBI with no corrections. A multireader
      multicase (MRMC) analysis only found significant patient and patient-strategy
      effects. The conflicting results concerning AC from this study and the previous
      one may revolve around lesion masking effects, which, by design, were not a
      factor in the current study.

PMID- 19169429
TI  - The Influence of Photon Attenuation on Tumor-to-Background and Signal-to-Noise
      Ratios for SPECT Imaging.
AB  - Expanding on the work of Nuyts et. al [1], Bai et. al. [2], and Bai and Shao [3],
      who all studied the effects of attenuation and attenuation correction on tumor-to
      background ratios and signal detection, we have derived a general expression for
      the tumor-to-background ratio (TBR) for SPECT attenuated data that have been
      reconstructed with a linear, non-iterative reconstruction operator O. A special
      case of this is when O represents discrete filtered back-projection (FBP). The
      TBR of the reconstructed, uncorrected attenuated data (TBR(no-AC)) can be written
      as a weighted sum of the TBR of the FBP-reconstructed unattenuated data
      (TBR(FBP)) and the TBR of the FBP-reconstructed "difference" projection data
      (TBR(diff)). We evaluated the expression for TBR(no-AC) for a variety of objects
      and attenuation conditions. The ideal observer signal-to-noise ratio (SNR(ideal))
      was also computed in projection space, in order to obtain an upper bound on
      signal detectability for a signal-known-exactly/background-known-exactly
      (SKE/BKE) detection task. The results generally show that SNR(ideal) is lower for
      tumors located deeper within the attenuating medium and increases for tumors
      nearer the edge of the object. In addition, larger values for the uniform
      attenuation coefficient MU lead to lower values for SNR(ideal). The TBR for FBP
      reconstructed, uncorrected attenuated data can both under- and over-estimate the
      true TBR, depending on several properties of the attenuating medium, including
      the shape of the attenuator, the uniformity of the attenuator, and the degree to
      which the data are attenuated.

PMID- 19169430
TI  - Emotional Distress, Drinking, and Academic Achievement across the Adolescent Life
      Course.
AB  - Our study of the adolescent life course proposes that substantial maturation
      occurs within three intertwined arenas of development: the social, the
      psychological, and the normative attainment. Further, each arena may be linked,
      respectively, to three youth problem dimensions: drinking, depressive affect, and
      academic achievement. We use latent growth curves and the Youth Development Study
      (effective N=856) to track a panel of teens from their freshman to senior year in
      high school. There are 54.4% girls and 45.6% boys, and 75.7% non-Hispanic whites
      and 24.3% other races/ethnicities. Two research goals are addressed: (1) estimate
      each dimension's unique developmental trajectory across high school, and (2)
      model the dimensions together in order to assess their reciprocal influences.
      While mean levels in all three dimensions increased over time, distinct
      developmental patterns were observed, especially in drinking and depression. For
      example, more drinking occasions-a social activity for most teens-may help
      assuage some teens' emotional distress, especially girls'. These patterns suggest
      a synergistic relationship between the social and psychological arenas of
      development. Contrary to expectation, higher freshman depressive affect was
      associated with a significantly sharper increase in GPA over time for girls.

PMID- 19169431
TI  - Impact of respiratory motion on the detection of small pulmonary nodules in SPECT
      imaging.
AB  - The objective of this investigation is to determine the impact of respiratory
      motion on the detection of small solitary pulmonary nodules (SPN) in single
      photon emission computed tomographic (SPECT) imaging. We have previously modeled
      the respiratory motion of SPN based on the change of location of anatomic
      structures within the lungs identified on breath-held CT images of volunteers
      acquired at two different stages of respiration. This information on respiratory
      motion within the lungs was combined with the end-expiration and time-averaged
      NCAT phantoms to allow the creation of source and attenuation maps for the normal
      background distribution of Tc-99m NeoTect. With the source and attenuation
      distribution thus defined, the SIMIND Monte Carlo program was used to produce
      SPECT projection data for the normal background and separately for each of 150
      end-expiration and time-averaged simulated 1.0 cm tumors. Normal and tumor SPECT
      projection sets each containing one lesion were combined with a clinically
      realistic noise level and counts. These were reconstructed with RBI-EM using 1)
      no correction (NC), 2) attenuation correction (AC), 3) detector response
      correction (RC), and 4) attenuation correction, detector response correction, and
      scatter correction (AC_RC_SC). The post-reconstruction parameters of number of
      iterations and 3-D Gaussian filtering were optimized by human-observer studies.
      Comparison of lesion detection by human-observer LROC studies reveals that
      respiratory motion degrades tumor detection for all four reconstruction
      strategies, and that the magnitude of this effect is greatest for NC and RC, and
      least for AC_RC_SC. Additionally, the AC_RC_SC strategy results in the best
      detection of lesions.

PMID- 19169432
TI  - Thirty-year Survival for Black and White Hypertensive Individuals in the Evans
      County Heart Study and the Hypertension Detection and Follow-up Program.
AB  - The Evans County Heart Study (ECHS), initiated in 1960, was one of the first
      major studies to document cardiovascular disease (CVD) risks for African
      Americans and Caucasians with elevated blood pressures. In the early 1970's, the
      Hypertension Detection and Follow-up Program (HDFP), with a site in Georgia (HDFP
      GA) was one of the first major studies to demonstrate that treating hypertension
      with stepped care (SC), versus referred care (RC), has better short-term
      outcomes. With this background, study objectives were to evaluate 30-year
      survival and cardiovascular outcomes of the HDFP-GA and to compare outcomes of
      these patients with 1619 hypertensive individuals (30-69 years of age) from the
      ECHS. HDFP-GA patients included 688 individuals (black [n=267]; white [n=421])
      randomized to RC (n=341) and SC (n=347). The ECHS was comprised of 733 black and
      886 white hypertensives. All-cause mortality and CVD mortality were assessed in
      the HDFP-GA and compared to the ECHS hypertensives. After 30-years of follow-up,
      65.7% of the HDFP-GA cohort had died compared with a similar 65.8% of the ECHS
      hypertensives. However, CVD mortality rates, while similar for the SC and RC
      arms, were lower than in the HDFP-GA total study group than the hypertensive
      participants of ECHS (32.6% vs. 40.3% p<.001). CVD survival rates for both SC and
      RC HDFP-GA arms were significantly better than population-based hypertensive
      individuals in the ECHS, with consistent benefits in all four race-sex groups.
      These results identify the importance of long-term follow-up of individuals in
      hypertension studies and trials that include CVD outcomes.

PMID- 19169433
TI  - Current Methods for Recurrent Events Data with Dependent Termination: A Bayesian
      Perspective.
AB  - There has been a recent surge of interest in modeling and methods for analyzing
      recurrent events data with risk of termination dependent on the history of the
      recurrent events. To aid the future users in understanding the implications of
      modeling assumptions and modeling properties, we review the state of the art
      statistical methods and present novel theoretical properties, identifiability
      results and practical consequences of key modeling assumptions of several fully
      specified stochastic models. After introducing stochastic models with
      noninformative termination process, we focus on a class of models which allows
      both negative and positive association between the risk of termination and the
      rate of recurrent events via a frailty variable. We also discuss the relationship
      as well as the major differences between these models in terms of their
      motivations and physical interpretations. We discuss associated Bayesian methods
      based on Markov chain Monte Carlo tools, and novel model diagnostic tools to
      perform inference based on fully specified models. We demonstrate the usefulness
      of current methodology through an analysis of a data set from a clinical trial.
      In conclusion, we explore possible future extensions and limitations of the
      methodology.

PMID- 19169434
TI  - Culture and Personality Among European American and Asian American Men.
AB  - Personality differences between Asian American (N = 320) and European American
      men (N = 242) and also among Asian American ethnic groups (Korean, Chinese,
      Japanese, Filipino, and mixed Asian) are examined on the Big Five personality
      dimension. Personality structures for Asian Americans and European Americans
      closely replicate established norms. However, congruence is greater for European
      American and highly acculturated Asian American men than for low acculturated
      Asian American men. Similar patterns are found for the construct loss of face
      (LOF). Asian American men with a high concern for LOF are less similar in their
      personality structure to European American men than Asian American men with low
      LOF concern. Mean differences are also found among Asian American and European
      American men, who differ significantly on Extraversion, Conscientiousness,
      Openness, and Neuroticism. Results indicate that acculturation and LOF are
      significantly associated with these four personality dimensions for both Asian
      American and European American men.

PMID- 19169435
TI  - The Metal-Dependent Regulators FurA and FurB from Mycobacterium Tuberculosis.
AB  - The ferric uptake regulators (Fur) form a large family of bacterial metal
      activated DNA-binding proteins that control a diverse set of genes at the
      transcriptional level. Mycobacterium tuberculosis, the causative agent of
      tuberculosis, expresses two members of the Fur family, designated FurA and FurB.
      Although both belong to the same family, they share only approximately 25%
      sequence identity and as a consequence, they differ significantly in some of
      their key biological functions. FurA appears to be a specialized iron-dependent
      regulator that controls the katG gene, which encodes for a catalase-peroxidase
      involved in the response of M. tuberculosis to oxidative stress. KatG is also the
      key mycobacterial enzyme responsible for the activation of the first-line
      tuberculosis drug Isoniazid. FurB in contrast requires Zn(2+) rather than Fe(2+),
      to bind to its target sequence in regulated genes, which include those involved
      in Zn(2+)-homeostasis. Recent biochemical, crystallographic and spectroscopic
      data have now shed light on the activation and metal discrimination mechanisms in
      this protein family.

PMID- 19169436
TI  - Delayed heart block after temporary balloon occlusion of a secundum atrial septal
      defect.

PMID- 19169438
TI  - On the entropy of a hidden Markov process.
AB  - We study the entropy rate of a hidden Markov process (HMP) defined by observing
      the output of a binary symmetric channel whose input is a first-order binary
      Markov process. Despite the simplicity of the models involved, the
      characterization of this entropy is a long standing open problem. By presenting
      the probability of a sequence under the model as a product of random matrices,
      one can see that the entropy rate sought is equal to a top Lyapunov exponent of
      the product. This offers an explanation for the elusiveness of explicit
      expressions for the HMP entropy rate, as Lyapunov exponents are notoriously
      difficult to compute. Consequently, we focus on asymptotic estimates, and apply
      the same product of random matrices to derive an explicit expression for a Taylor
      approximation of the entropy rate with respect to the parameter of the binary
      symmetric channel. The accuracy of the approximation is validated against
      empirical simulation results. We also extend our results to higher-order Markov
      processes and to Renyi entropies of any order.

PMID- 19169437
TI  - The cellular response in neuroinflammation: The role of leukocytes, microglia and
      astrocytes in neuronal death and survival.
AB  - Neuroinflammation is a complex integration of the responses of all cells present
      within the CNS, including the neurons, macroglia, microglia and the infiltrating
      leukocytes. The initiating insult, environmental factors, genetic background and
      age/past experiences all combine to modulate the integrated response of this
      complex neuroinflammatory circuit. Here, we explore how these factors interact to
      lead to either neuroprotective versus neurotoxic inflammatory responses. We
      specifically focus on microglia and astrocytic regulation of autoreactive T cell
      responses.

PMID- 19169439
TI  - Family relationships during infancy and later mother and father vocabulary use
      with young children.
AB  - Very little previous research has considered the contributions of family
      relationships and interactions on the language input of mothers and fathers to
      their young children. This study examined the contributions of marital love and
      conflict, and broader family-level conflict, cohesion, and expressiveness to
      mother and father vocabulary in triadic interactions with their young children in
      70 dual-earner families. It was found that after controlling for parent
      sensitivity and parent directive behavior, marital love and family conflict when
      children were 12 months of age were significant predictors of both father
      vocabulary and mother vocabulary to children at 24 months of age. In families
      with higher levels of marital love when children were 12 months of age, mothers
      and fathers used a more diverse vocabulary with their 24 month-old children. In
      families with lower levels of family conflict when children were 12 months of
      age, mothers and fathers used a more diverse vocabulary with their 24 month-old
      children.

PMID- 19169440
TI  - Keeping the science in the art and science of dentistry.

PMID- 19169441
TI  - Effects of regular and whitening dentifrices on remineralization of bovine enamel
      in vitro.
AB  - OBJECTIVE: To compare in vitro the remineralizing effects of different regular
      dentifrices and whitening dentifrices (containing pyrophosphates) on
      predemineralized enamel. METHOD AND MATERIALS: Specimens from 84 bovine incisors
      were embedded in epoxy resin, partly covered with nail varnish, and demineralized
      in a lactic acid solution (37 degrees C, pH 5.0, 8 days). Parts of the
      demineralized areas were covered with nail varnish, and specimens were randomly
      assigned to 6 groups. Subsequently, specimens were exposed to a remineralizing
      solution (37 degrees C, pH 7.0, 60 days) and brushed 3 times a day (1:3 slurry
      with remineralizing solution) with 1 of 3 regular dentifrices designed for
      anticaries (group 1, amine; group 2, sodium fluoride) or periodontal (group 3,
      amine/stannous fluoride) purposes or whitening dentifrice containing
      pyrophosphates (group 4, sodium fluoride). An experimental dentifrice (group 5,
      without pyrophosphates/fluorides) and a whitening dentifrice (group 6,
      monofluorophosphate) served as controls. Mineral loss and lesion depths were
      evaluated from contact microradiographs, and intergroup comparisons were
      performed using the closed-test procedure (alpha =.05). RESULTS: Compared to
      baseline, specimens brushed with the dentifrices containing stannous/amine
      fluorides revealed significant mineral gains and lesion depth reductions (P <
      .05). Concerning the reacquired mineral, the whitening dentifrice performed worse
      than the regular dentifrices (P > .05), while mineral gain, as well as lesion
      depth, reduction was negligible with the control groups. CONCLUSION: Dentifrices
      containing pyrophosphates perform worse than regular dentifrices but do not
      necessarily affect remineralization. Unless remineralizing efficacy is proven,
      whitening dentifrices should be recommended only after deliberate consideration
      in caries-prone patients.

PMID- 19169442
TI  - Clinical success of deproteinization in hypocalcified amelogenesis imperfecta.
AB  - OBJECTIVE: To determine the effect of deproteinization on the success of
      composite crowns in hypocalcified amelogenesis imperfecta-affected permanent
      teeth in intraoral conditions. METHOD AND MATERIALS: A total of 32 permanent
      teeth in 4 healthy children with hypocalcified amelogenesis imperfecta were
      restored with strip crowns and composite resin. Teeth on the left side of the jaw
      were selected as the control group, and teeth on the right side of the jaw were
      selected as the treatment group. In the treatment group, a solution of 5% sodium
      hypochlorite was applied for 1 minute after acid conditioning of tooth surfaces.
      Clinical success was determined by USPHS modified Ryge criteria up to 36 months.
      RESULTS: The deproteinization procedure had no effect on the anatomic form of the
      restorations. The cervical integrity of the restorations in both groups showed
      inferior results after 36 months compared to baseline. For both groups, no
      recurrence of caries was observed. CONCLUSION: The deproteinization had no
      significant effect on the success of the adhesive restorations; however,
      composite restorations were clinically successful in children affected by
      hypocalcified amelogenesis imperfecta in long-term follow-up.

PMID- 19169443
TI  - Primary herpetic gingivostomatitis in children and adults.
AB  - OBJECTIVES: To investigate if the onset of primary herpetic gingivostomatitis
      (PHG) is shifting toward an adult age and compare the clinical characteristics of
      PHG between children and adults. METHOD AND MATERIALS: The charts of patients
      diagnosed with PHG in an oral medicine clinic in Bucharest, Romania, over a 10
      year period were revisited. Diagnosis was based on history, clinical data, and
      laboratory confirmation (Tzanck cytology, polymerase chain reaction [PCR], or
      immunofluorescence). Seventy-three cases (38 females, 35 males) were included.
      The age range was between 22 months and 53 years, with a mean age of 18.6 years.
      All patients were healthy with no suspicion of HIV infection or immunodeficiency.
      RESULTS: Nearly 48% (47.94%) of the sample were in the young adult group. General
      symptoms (fever, malaise, and lymphadenopathy) were equally present in children
      and adults. The most involved areas were the gingiva, vermilion border, and
      tongue. No differences in the extent of lesions were observed between children
      and adults. Inflammatory gingivitis and pharyngotonsillitis were more frequent in
      children than in adults although their frequency was less than expected.
      CONCLUSIONS: PHG was more frequently observed in young adults than in children.
      No significant differences between children and adults in the severity of
      infection were observed. Most of the patients presented widespread lesions.

PMID- 19169444
TI  - Simulated fatigue resistance of composite resin versus porcelain CAD/CAM overlay
      restorations on endodontically treated molars.
AB  - OBJECTIVE: To assess the influence of material selection (porcelain versus
      composite resin) for overlay-type restoration of endodontically treated molars
      and its effect on the in vitro fatigue resistance and failure mode. METHOD AND
      MATERIALS: A standardized tooth preparation was applied to 30 extracted molars,
      including root canal treatment, 3-mm coverage of all cusps, a mesial box 1.5 mm
      below the cementoenamel junction (CEJ), a distal box in enamel, a glass-ionomer
      base, and immediately sealed dentin. Using the Cerec machine (Sirona), all teeth
      were restored with an overlay of standardized thickness and occlusal anatomy.
      Fifteen restorations were milled in the ceramic Vita MKII block (Vident) and the
      other 15 using the composite resin Paradigm MZ100 block (3M ESPE). The intaglio
      surfaces of the ceramic restorations were etched and silanated. The intaglio
      surfaces of the composite resin overlays were airborne-particle abraded and
      silanated. Preparations were airborne-particle abraded and etched before
      restoration insertion. All restorations were adhesively luted with an adhesive
      resin (Optibond FL, Kerr) and a light-curing composite resin (Filtek Z100, 3M
      ESPE). Cyclic isometric chewing (5 Hz) was simulated, starting with a load of 200
      N (5,000 cycles), followed by stages of 400, 600, 800, 1,000, 1,200, and 1,400 N
      at a maximum of 30,000 cycles each. Samples were loaded until fracture or to a
      maximum of 185,000 cycles. RESULTS: MKII overlays fractured at a mean load of
      1,147 N, and none of them withstood all 185,000 loading cycles (survival = 0%);
      with MZ100, the survival rate was 73%. With MKII, 40% of the fractures ended
      below the CEJ; with MZ100, only 25% did. CONCLUSIONS: Composite resin MZ100
      increased the fatigue resistance of overlay-type restorations in endodontically
      treated molars when compared to porcelain MKII. The efficiency of the bond
      strategy (immediate dentin sealing) was demonstrated by the absence of adhesive
      failures.

PMID- 19169445
TI  - Ewing sarcoma of the maxilla: a rare presentation.
AB  - Ewing sarcoma is a highly malignant neoplasm, which very rarely involves the head
      and neck region. Only a few cases have been reported in the maxila or palate.
      This case is being reported for its rarity. A patient presented to the Department
      of Oral Pathology, Faculty of Dental Sciences, CSM Medical University, Lucknow,
      India, with a lesion expanding the nasal cavity and posteriorly reaching up to
      the anterior border of nasopharynx and inferiorly causing the destruction of the
      hard palate extending into the oral cavity. The biopsy specimen
      histopathologically revealed undifferentiated malignant neoplasm, and the
      definitive diagnosis of Ewing sarcoma was made with immunohistochemistry. The
      patient underwent surgical excision of the lesion followed by radiotherapy and
      chemotherapy.

PMID- 19169446
TI  - Evaluation of the substantivity in saliva of different forms of application of
      chlorhexidine.
AB  - OBJECTIVE: To evaluate the in vivo antimicrobial activity of different forms of
      application of chlorhexidine digluconate (CHX). METHOD AND MATERIALS: A group of
      10 volunteers performed mouth rinsings with a 0.2% and 0.12% solution of CHX and
      applied CHX in the form of a 0.2% gel, a 0.2% and a 0.12% spray and a swab
      impregnated with a 0.2% solution. Samples of saliva were taken at baseline; 30
      seconds; and 1, 3, 5, and 7 hours after each application. An epifluorescence
      microscopy technique (BacLight Live/Dead stain) was used to evaluate bacterial
      vitality. RESULTS: Bacterial vitality under basal conditions was 92%. At 30
      seconds after CHX application, the lowest levels of viable bacteria were detected
      with the 0.2% and 0.12% solutions (1% and 8%, respectively). After 3 hours, the
      percentage of live bacteria achieved with the gel and sprays was similar to the
      basal figures (80% to 91%). At 7 hours, bacterial vitality recovered basal
      percentages, except with the 0.2% solution (77%). CONCLUSION: The 0.2% solution
      of CHX had the greatest sustained antimicrobial effect on the salivary flora,
      confirming the influence of the concentration and form of application on CHX
      substantivity.

PMID- 19169447
TI  - Influence of Nd:YAG laser irradiation on microtensile bond strength of adhesive
      systems to sound or carious dentin.
AB  - OBJECTIVE: To evaluate the microtensile bond strength of 2 adhesive systems
      (Adper Single Bond Plus [3M ESPE] and Clearfil SE Bond [Kuraray]) to carious or
      normal dentin, with or without previous treatment with Nd:YAG laser or Nd:YAG
      laser associated with fluoride. METHOD AND MATERIALS: Dentin surfaces of 60 human
      third molars were exposed. Teeth were divided into 12 groups; groups 1 to 6 were
      submitted to pH cycling for artificial caries, and groups 7 to 12 remained with
      normal dentin. Dentin surfaces received 3 treatments: laser Nd:YAG irradiation
      (60 mJ, 15 Hz, and 0.9 W) for 1 minute; laser Nd:YAG irradiation associated with
      fluoride in gel; and no treatment (controls). In experimental groups, adhesive
      systems were applied in accordance with the manufacturers' instructions, and a
      composite resin block (Filtek Z250, 3M ESPE) was made incrementally for the
      microtensile bond strength test. The teeth were sectioned serially in both x and
      y directions, and sticks were submitted to microtensile bond strength testing in
      a universal testing machine. RESULTS: According to ANOVA and Tukey (P < .05), the
      highest mean bond strengths were obtained in groups of normal dentin treated with
      Clearfil SE Bond (40.65 MPa) and Single Bond (34.2 MPa). The presence of carious
      dentin significantly decreased the mean bond strengths of the 2 adhesive systems
      whether or not they were previously laser irradiated. Nevertheless, Clearfil SE
      Bond presented the best microtensile bond strength on an irradiated surface.
      Moreover, laser irradiation associated with fluoride also decreased the bond
      strength values of the 2 adhesive systems. CONCLUSION: After excavating a cavity
      with caries-affected dentin, the use of Nd:YAG laser followed by a self-etching
      adhesive system is the best clinical choice when considering bond strength,
      compared with the total etching- based system and laser.

PMID- 19169448
TI  - Plain film and CBCT findings in a case of bisphosphonate-related osteonecrosis of
      the jaw.
AB  - Imaging, along with clinical examination, plays a key role in determining the
      presence and extent of bisphosphonate-related osteonecrosis of the jaw (BRONJ).
      In this case, cone-beam computerized tomography (CBCT) was used to detect a large
      sequestrum and hyperstotic bone, leading to a diagnosis of bisphosphonate-related
      osteonecrosis of the jaw in a patient with a history of oral bisphosphonate use
      for treatment of osteoporosis. The radiographic features of this case of BRONJ
      are discussed.

PMID- 19169449
TI  - Apocrine papillary cystadenoma of a minor salivary gland on the lower lip: case
      presentation.
AB  - Cystadenomas are a rare, painless, and slow-growing benign epithelial tumor of
      the salivary gland. This article describes the case of a papillary cystadenoma in
      the lower lip of a 46-year-old man. The lesion was removed using a carbon dioxide
      laser, and there were no signs of recurrence 1 year postoperatively.

PMID- 19169450
TI  - Polymers and single molecule fluorescence spectroscopy, what can we learn?
AB  - This tutorial review summarizes the most important results and developments in
      the field of polymer science by means of single molecule fluorescence
      spectroscopy (SMFS) at ambient temperatures. A broad range of topics will be
      addressed and it will be discussed which single molecule methods are suitable to
      get the maximum amount of information about polymer structure, polymer dynamics
      and the photophysics of incorporated or embedded dye molecules. In particular, we
      will report on the use of polymer films for immobilization of molecules, the
      visualization of dynamics near the glass transition temperature Tg, the reptation
      of polymer chains, the conformation adopted by polymer chains and the in situ
      observation of the polymerization reaction itself.

PMID- 19169451
TI  - DNA-templated nanofabrication.
AB  - Nanofabrication, or the organizational control over matter at the nanometre
      scale, is an intriguing scientific challenge requiring multidisciplinary tools
      for its solution. DNA is a biomolecule that can be combined with other nanometre
      scale entities through chemical self-assembly to form a broad variety of
      nanomaterials. In this tutorial review we present the principles that allow DNA
      to interact with other chemical species, and describe the challenges and
      potential applications of DNA as a template for making both biological and
      inorganic features with nanometre resolution. As such, this report should be of
      interest to chemists, surface and materials scientists, biologists, and
      nanotechnologists, as well as others who seek to use DNA in nanofabrication.

PMID- 19169452
TI  - Total chemical synthesis of proteins.
AB  - This tutorial review outlines the modern ligation methods that enable the
      efficient total chemical synthesis of enzymes and other protein molecules. Key to
      this success is the chemoselective reaction of unprotected synthetic peptides
      ('chemical ligation'). Notably, native chemical ligation enables the reaction of
      two unprotected peptides in aqueous solution at neutral pH to form a single
      product in near quantitative yield. Full-length synthetic polypeptides are folded
      to form the defined tertiary structure of the target protein molecule, which is
      characterized by mass spectrometry, NMR, and X-ray crystallography, in addition
      to biochemical and/or biological activity.

PMID- 19169453
TI  - New methodologies in the construction of dendritic materials.
AB  - Dendritic polymers are highly branched polymer structures, with complex,
      secondary architectures and well-defined spatial location of functional groups.
      Due to their unique physical and chemical features, applications in areas such as
      targeted drug-delivery, macromolecular carriers, catalysis, sensors, light
      harvesting, surface engineering and biomimetic materials have been proposed.
      However, only a few dendritic materials have been exploited commercially due to
      time consuming syntheses and the generation of significant waste/presence of
      unreacted starting materials. This tutorial review describes traditional
      synthesis of dendritic materials as well as recent advances in synthetic
      strategies, for example the use of Click chemistry, as a tool to efficiently
      obtain complex, functional dendritic structures.

PMID- 19169454
TI  - Metal-free double helices from abiotic backbones.
AB  - There is a general interest in designing biomimetic materials, such as the double
      helical structures of biopolymers, by the self-assembly of synthetic organic
      moieties. This interest stems from their structural versatility,
      biocompatibility, robustness and a relative experimental simplicity. The self
      assembly process requires a combination of several non-covalent interactions
      between two intertwined strands. Besides the combination of metal-ligand binding,
      base pair interactions and peptide stacking interactions, in the last few years,
      hybridized synthetic foldamers have proven to be useful in this context. The
      molecular rigidity and the extent of intra- vs. intermolecular interactions
      within the strand play an important role in the intertwining processes. A dynamic
      equilibrium exists between the monomer and the dimer. In general, the combination
      of the enthalpic gain (from the interaction of the two strands) and entropic loss
      (upon hybridization) controls the duplex formation. There are now a variety of
      metal-free double helices from abiotic backbones, with potential applications in
      antigene therapy, studies on evolution and conducting materials. A tutorial
      review of some general guidelines and illustrative examples is presented.

PMID- 19169455
TI  - Multifunctional nanostructured materials for multimodal imaging, and simultaneous
      imaging and therapy.
AB  - Nanotechnology offers tremendous potential for future biomedical technology. Due
      to their unique characteristics including superparamagnetic or fluorescent
      properties, and small size comparable to biomolecules, nanostructured materials
      have emerged as novel bioimaging, diagnostic, and therapeutic agents for the
      future medical field. Especially, the combinations of various nanostructured
      materials with different properties can offer synergetic multifunctional
      nanomedical platforms, which make it possible to accomplish multimodal imaging,
      and simultaneous diagnosis and therapy. Moreover, the conjugation of targeting
      moieties on the surface of these multifunctional nanomaterials gives them
      specific targeted imaging and therapeutic properties. In this tutorial review, we
      will summarize the recent reports on the fabrication strategies of
      multifunctional nanoplatforms and their applications to targeted multimodal
      imaging and simultaneous diagnosis and therapy.

PMID- 19169456
TI  - Bioorganometallic chemistry--from teaching paradigms to medicinal applications.
AB  - In undergraduate level organometallic chemistry courses students are usually
      taught that organometallic compounds are toxic and unstable in air and water.
      While this is true of many complexes, some are also non-toxic and stable in air
      and water. Indeed, bioorganometallic chemistry, the study of biomolecules or
      biologically active molecules that contain at least one carbon directly bound to
      a metal, is a thriving subject, and air and water stability is a general pre
      requisite. This interdisciplinary field is located at the borderline between
      chemistry, biochemistry, biology and medicine. In this tutorial review, various
      aspects of bioorganometallic chemistry are introduced, with the main emphasis on
      medicinal organometallic compounds. Organometallic therapeutics for cancer, HIV
      and malaria and other medicinal applications are described. It is also shown how
      rational ligand design has led to new improved therapies much in the same way
      that an organometallic chemist working in catalysis will design new ligands for
      improved activities.

PMID- 19169457
TI  - Two-dimensional supramolecular self-assembly: nanoporous networks on surfaces.
AB  - This tutorial review addresses the formation and properties of surface-confined
      molecular networks as revealed with scanning probe microscopy tools, especially
      scanning tunneling microscopy. It could be of interest to all interested in
      surface nano-engineering, and supramolecular chemistry on surfaces. More
      specifically, this review highlights recent developments in the design of regular
      nanoporous networks, with a pore diameter ranging from 1 nm to more than 10 nm.
      The principles leading to their formation are treated in detail and the various
      functionalities of these porous networks are demonstrated.

PMID- 19169458
TI  - Design and synthesis of porphyrin-containing catenanes and rotaxanes.
AB  - Catenanes and rotaxanes containing porphyrin subunits have become popular
      synthetic targets because of the large variety of available synthetic strategies
      including the coordination chemistry of metallated porphyrins, coupled with the
      many attractive physical properties of porphyrins. This tutorial review outlines
      various synthetic approaches and templating strategies that have been used to
      prepare a range of mechanically interlocked architectures that incorporate
      porphyrins as fundamental subunits either grafted onto macrocycles or as
      stoppers. These species are of interest in relation to recreating natural
      processes such as the photosynthetic apparatus or enzyme binding sites.

PMID- 19169459
TI  - Recent development and improvement for boron hydride-based catalytic asymmetric
      reduction of unsymmetrical ketones.
AB  - Catalytic asymmetric reduction of prochiral ketones with hydrides such as boranes
      and borohydrides is one of the simplest and the most convenient methods for
      obtaining chiral alcohols. This tutorial review describes the most significant
      advances recently achieved for enhancing the enantioselectivity and
      practicability of the reduction using this methodology. The review covers the
      development of new homogeneous and/or immobilized catalysts for asymmetric
      reduction using borane or borohydride reagents and practical improvement of the
      well-known oxazaborolidine (OAB)-catalysed reduction through developing more
      stable, cost effective and recoverable OABs, scalable and environmental friendly
      borane sources, and one-pot procedures for the reduction.

PMID- 19169460
TI  - Understanding enzyme immobilisation.
AB  - Enzymes are versatile catalysts in the laboratory and on an industrial scale. To
      broaden their applicability in the laboratory and to ensure their (re)use in
      manufacturing the stability of enzymes can often require improvement.
      Immobilisation can address the issue of enzymatic instability. Immobilisation can
      also help to enable the employment of enzymes in different solvents, at extremes
      of pH and temperature and exceptionally high substrate concentrations. At the
      same time substrate-specificity, enantioselectivity and reactivity can be
      modified. However, most often the molecular and physical-chemical bases of these
      phenomena have not been elucidated yet. This tutorial review focuses on the
      understanding of enzyme immobilisation.

PMID- 19169461
TI  - Azido-mediated systems showing different magnetic behaviors.
AB  - Azido has been one of the well used bridging ligands in the construction of
      magnetic molecule materials, which has stimulated considerable interest in
      magnetochemistry. This tutorial review is concentrated on the study of azido
      metal compounds with their magnetochemistry and consists of eight main sections.
      The first section offers an introduction to azido complexes and some important
      results obtained from magneto-structural correlation in azido complexes which
      will be referred to in the following sections. The next six sections give
      overviews of azido-mediated ferromagnets, ferrimagnets, canted (weak)
      ferromagnets, antiferromagnets, single molecule magnets (SMMs) and single chain
      magnets (SCMs), and metamagnets. The last section is the conclusion and gives a
      perspective of azido-mediated magnets.

PMID- 19169462
TI  - Supported metal nanoparticles on porous materials. Methods and applications.
AB  - Nanoparticles are regarded as a major step forward to achieving the
      miniaturisation and nanoscaling effects and properties that have been utilised by
      nature for millions of years. The chemist is no longer observing and describing
      the behaviour of matter but is now able to manipulate and produce new types of
      materials with specific desired physicochemical characteristics. Such materials
      are receiving extensive attention across a broad range of research disciplines.
      The fusion between nanoparticle and nanoporous materials technology represents
      one of the most interesting of these rapidly expanding areas. The harnessing of
      nanoscale activity and selectivity, potentially provides extremely efficient
      catalytic materials for the production of commodity chemicals, and energy needed
      for a future sustainable society. In this tutorial review, we present an
      introduction to the field of supported metal nanoparticles (SMNPs) on porous
      materials, focusing on their preparation and applications in different areas.

PMID- 19169463
TI  - Molecular recognition of bilayer vesicles.
AB  - Vesicles have been a versatile topic of research in chemistry ever since the
      discovery that, besides phospholipids, synthetic amphiphiles can also form
      molecular bilayers enclosing a small aqueous compartment. Non-covalent
      interactions of receptors and ligands or hosts and guests at vesicle surfaces
      resemble recognition processes at biological membranes, including cell
      recognition, adhesion and fusion. Molecular recognition at membranes is often
      mediated by a multivalent instead of a monovalent interaction. This tutorial
      review describes the basics as well as the latest developments in biomimetic
      supramolecular chemistry of bilayer vesicles. We describe how molecular
      recognition can mediate the interaction between vesicles, and how the biomimetic
      supramolecular chemistry of vesicles furthers our understanding of biological
      membranes.

PMID- 19169464
TI  - Coordination and organometallic compounds as anion receptors and sensors.
AB  - In this tutorial review the wide-ranging use of metal ions in anion receptors is
      discussed with an emphasis on diversity and applications in sensing and soft
      materials. Metal-containing receptors are categorised according to the role of
      the metal as a structural unit, as a Lewis-acidic binding site or as part of a
      redox-active or luminescent reporter group. The differing chemistry of
      substitutionally inert metal complexes in anion hosts and metal-anion-ligand self
      assembly processes is highlighted. The use of anion binding coordination polymer
      systems in anion separations and in supramolecular gels is also examined.

PMID- 19169465
TI  - Anion receptor chemistry: highlights from 2007.
AB  - This critical review includes advances in anion complexation in the year 2007.
      The review covers anion receptors that employ amides and thioamides, pyrroles and
      indoles, ureas and thioureas, guanidinium, ammonium, and imidazolium groups and
      receptors containing hydroxyl groups. In addition, receptors containing metal
      ions or Lewis acids are discussed along with anion-pi interactions and the
      membrane transport of anionic species by synthetic transporters and channels (204
      references).

PMID- 19169466
TI  - Self-assembled pi-stacks of functional dyes in solution: structural and
      thermodynamic features.
AB  - This critical review provides an overview on the formation of pi-stacks of
      functional dyes in solution, aiming to acquaint young researchers with this
      topical research field and to stimulate further advance in supramolecular dye
      chemistry. Different mathematical models that have been proposed and applied for
      the description of aggregation equilibria of pi-systems in solution are
      discussed. The factors that have significant impact on the structural features of
      aggregates and the thermodynamics of pi-pi stacking such as electrostatic
      interactions, size and geometry of the dye molecules are covered in this review.
      A comparison of the binding strength is made for different classes of functional
      pi-conjugated systems, from simple benzene to more extended polycyclic
      hydrocarbon molecules, including triphenylenes and hexabenzocoronenes,
      heteroaromatic porphyrins and phthalocyanines, quadrupolar naphthalene and
      perylene bisimides, dipolar or even zwitterionic merocyanines and squaraines, and
      some macrocyclic dyes. Solvent effects on binding constants are analysed by
      linear free energy relationships with various solvent polarity scales (98
      references with multiple entries).

PMID- 19169467
TI  - Amino acid containing anion receptors.
AB  - Nature has devised highly efficient and selective ways of recognizing anionic
      substrates by using surprisingly few building blocks the most important of which
      are the amino acids serine, tryptophane, and arginine in addition to NH groups
      along the protein backbone. Deliberate use of amino acids for the construction of
      abiotic anion receptors could lead to systems that mimic the anion coordinating
      properties of anion binding proteins. With this aim in mind several groups have
      focused their attention on the development of anion receptors containing amino
      acid building blocks and came up with remarkably efficient systems. This critical
      review summarizes the different approaches (174 references).

PMID- 19169468
TI  - Amide bond formation: beyond the myth of coupling reagents.
AB  - Amide bond formation is a fundamentally important reaction in organic synthesis,
      and is typically mediated by one of a myriad of so-called coupling reagents. This
      critical review is focussed on the most recently developed coupling reagents with
      particular attention paid to the pros and cons of the plethora of "acronym" based
      reagents. It aims to demystify the process allowing the chemist to make a
      sensible and educated choice when carrying out an amide coupling reaction (179
      references).

PMID- 19169469
TI  - Asymmetric organocatalysis by chiral Bronsted bases: implications and
      applications.
AB  - Chiral, metal-free Bronsted bases have been demonstrated capable of catalyzing
      several types of C-C and C-X bond-forming reactions with high chemical and
      stereochemical efficiency, thereby complementing other major organocatalytic
      asymmetric approaches such as enamine catalysis. This critical review describes
      the most fundamental developments in the area, which have been documented in the
      last couple of years, along with major mechanistic implications. Discussion
      includes the limitations of the present protocols, identifies the most salient
      gaps, and gives a prospect of future improvements and applications (122
      references).

PMID- 19169470
TI  - Getting your report seen in and beyond ABE&M.

PMID- 19169471
TI  - E449X mutation in the thyroid hormone receptor beta associated with autoimmune
      thyroid disease and severe neuropsychomotor involvement.
AB  - OBJECTIVE: To report the clinical and molecular aspects of a patient with a
      diagnosis of Resistance to Thyroid Hormone (RTH) harboring the E449X mutation
      associated with autoimmune thyroid disease and severe neuropsychomotor
      retardation. METHODS: We present a case report including clinical and laboratory
      findings, and molecular analysis of a Brazilian patient with RTH. RESULTS: A 23
      year old male presented hyperactivity disorder, attention deficit, delayed
      neuropsychomotor development, and goiter. Since the age of 1 year and 8 months,
      his mother had sought medical care for her son for the investigation of delayed
      neuropsychomotor development associated with irritability, aggressiveness,
      recurrent headache, profuse sudoresis, intermittent diarrhea, polyphagia, goiter,
      and low weight. Laboratory tests revealed normal TSH, increased T3, T4,
      antithyroglobulin and antimicrosomal antibody titers. Increasing doses of
      levothyroxine were prescribed, reaching 200 microg/day, without significant
      changes in his clinical-laboratory picture. Increasing doses of tiratricol were
      introduced, with a clear clinical improvement of aggressiveness, hyperactivity,
      tremor of the extremities, and greater weight gain. Molecular study revealed a
      nonsense mutation in exon 10, in which a substitution of a guanine to tyrosine in
      nucleotide 1345 (codon 449) generates the stop codon TAA, confirming the
      diagnosis of RTH. CONCLUSION: This patient has severe neuropsychomotor
      retardation not observed in a single previous report with the same mutation. This
      may reflect the lack of a genotype-phenotype correlation in affected cases with
      this syndrome, suggesting that genetic variability of factors other than beta
      receptor of thyroid hormone (TRbeta) might modulate the phenotype of RTH.

PMID- 19169472
TI  - HRPT2-related familial isolated hyperparathyroidism: could molecular studies
      direct the surgical approach?
AB  - It is still debatable which is the best management to familial forms of
      hyperparathyroidism. Conservative, minimally invasive or aggressive surgical
      approaches have been proposed from different groups around the world. Our
      objective was to study the gene mutation, expression of HRPT2 and the clinical
      outcome after 32 years of follow-up in one Brazilian kindred with familial
      isolated hyperparathyroidism (FIHP). Clinical and biochemical data, direct
      sequencing of the HRPT2 gene, analysis of parafibromin expression using RT-PCR,
      and immunohistochemistry were done. A nonsense mutation was found in exon 1
      (c.96G>A)(p.Trp32X) in all affected members studied. Using RT-PCR, mRNA
      transcription was altered with complete absence of both transcripts in tumor
      tissue. Immunohistochemical analysis of tumors showed loss of parafibromin
      immunoreactivity. In this kindred there was a high prevalence of recurrence
      (75%), or persistence after less than subtotal parathyroidectomy that led us to
      consider a more aggressive surgical approach should be discussed among the
      affected family members, once surgical criteria was met. We concluded that it is
      necessary to individualize the surgical approach for HRPT2-related
      hyperparathyroidism until we can gather a better phenotype-genotype correlation
      in larger series, to best define their treatment.

PMID- 19169473
TI  - Absence of mutations in Pax6 gene in three cases of morning glory syndrome
      associated with isolated growth hormone deficiency.
AB  - Morning glory syndrome (MGS) is a congenital optic disc dysplasia often
      associated with craniofacial anomalies, especially basal encephalocele and
      hypopituitarism. Clinical signs are varied and often occult. The PAX6 gene is
      involved in ocular morphogenesis and is expressed in numerous ocular tissues
      during development especially in the developing central nervous system. The aim
      of the present study is to evaluate PAX6 in MGS associated with isolated growth
      hormone deficiency. Three pre-pubertal males (A, B and C) with MGS and short
      stature due to growth hormone deficiency, treated with recombinant human growth
      hormone with limited response, were reported. Two of them had basal
      encephalocele. Coding and non-coding sequences corresponding of PAX6 different
      transcripts were analyzed by direct sequencing. Nucleotide variations causing
      putative aminoacid change were not observed. Patient A presented the new
      IVS2+9G>A transition, whereas patients A and C were heterozygous for known single
      nucleotide polymorphisms (SNP) within the intron 4. In addition, two SNP
      heterozygoses were observed for patient C in both intron 9 and 13. Sequencing
      also revealed several nucleotide variations in patient B. Two heterozygoses for
      known polymorphisms were identified along with a novel C>A nucleotide change in
      intron 4. This patient also presented a low number on the TG repeat in intron 9
      and a new IVS11+33A>T transversion. Gene regulation and transcription of PAX6 are
      complex processes; there are two major protein isoforms, PAX6(-5a) and PAX6(+5a),
      and nine transcripts described. Furthermore, extra transcription regulatory
      elements have been postulated within PAX6 introns. Considering that neither
      population distributions on PAX6 polymorphism nor their linkeages with diseases
      have been reported, a functional effect due to alterations described here cannot
      be discarded.

PMID- 19169474
TI  - Prevalence of 15 mitochondrial DNA mutations among type 2 diabetic patients with
      or without clinical characteristics of maternally inherited diabetes and
      deafness.
AB  - The aim of the present study is to investigate the prevalence of ten described
      mitochondrial DNA (mtDNA) mutations in patients with type 2 diabetes, and search
      for new mutations in four mtDNA genes in a subgroup of patients with
      characteristics of maternally inherited diabetes and deafness (MIDD). These
      mutations were investigated in 407 type 2 diabetic patients without
      characteristics of mitochondrial diabetes ('classical' type 2 diabetes group) and
      in 38 type 2 diabetic patients with characteristics suggestive of MIDD. Through
      sequencing of four mtDNA genes in MIDD patients, we selected five others
      potentially pathogenic mutations that were also screened in the remaining
      patients. Overall, the frequency of the fifteen analyzed mutations was 36.84% in
      the MIDD group and 2.45% in the 'classical' type 2 diabetes group (p < 0.001). In
      conclusion, our study reinforces the importance of mtDNA mutations in the
      pathogenesis of MIDD.

PMID- 19169475
TI  - Clinical and genetic findings of five patients with WT1-related disorders.
AB  - AIM: To present phenotypic variability of WT1-related disorders. METHODS:
      Description of clinical and genetic features of five 46,XY patients with WT1
      anomalies. RESULTS: Patient 1: newborn with genital ambiguity; he developed Wilms
      tumor (WT) and chronic renal disease and died at the age of 10 months; the
      heterozygous 1186G>A mutation compatible with Denys-Drash syndrome was detected
      in this child. Patients 2 and 3: adolescents with chronic renal disease, primary
      amenorrhea and hypergonadotrophic hypogonadism; patient 2 had a gonadoblastoma.
      The heterozygous IVS9+4, C>T mutation, compatible with Frasier syndrome was
      detected. Patient 4: 9-year-old boy with aniridia, genital ambiguity,
      dysmorphisms and mental deficiency; a heterozygous 11p deletion, compatible with
      WAGR syndrome was detected. Patient 5: 2 months old, same diagnosis of patient 4;
      he developed WT at the age of 8 months. CONCLUSIONS: Constitutional abnormalities
      of WT1 cause gonadal and renal anomalies and predisposition to neoplasia and must
      be investigated in patients with ambiguous genitalia, chronic renal disease
      and(or) Wilms tumors; primary amenorrhea with chronic renal disease; and
      aniridia, genital ambiguity and dysmorphisms.

PMID- 19169476
TI  - Mutations in the vitamin D receptor gene in four patients with hereditary 1,25
      dihydroxyvitamin D-resistant rickets.
AB  - Mutations in the vitamin D receptor (VDR) are associated to the hereditary 1,25
      dihydroxivitamin D-resistant rickets. The objectives of this work are: search for
      mutations in the VDR and analyze their functional consequences in four Brazilian
      children presented with rickets and alopecia. The coding region of the VDR was
      amplified by PCR e direct sequenced. We identified three mutations: two patients
      had the same mutation in exon 7 at aminoacid position 259 (p.Q259E); one patient
      had a mutation in exon 8 at codon 319 (p.G319V) and another one had a mutation in
      exon 3 leading to a truncated protein at position 73 (p.R73X). Functional studies
      of the mutant receptors of fibroblast primary culture, from patients' skin biopsy
      treated with increasing doses of 1,25(OH)2 vitamin D showed that VDR mutants were
      unable to be properly activated and presented a reduction in 24-hydroxylase
      expression level.

PMID- 19169477
TI  - Atypical generalized lipoatrophy and severe insulin resistance due to a
      heterozygous LMNA p.T10I mutation.
AB  - Lipodystrophies are a group of heterogeneous disorders characterized by the loss
      of adipose tissue and metabolic complications. The main familial forms of
      lipodystrophy are Congenital Generalized Lipodystrophy and Familial Partial
      Lipodystrophy (FPLD). FPLD may result from mutations in the LMNA gene. Besides
      FPLD, mutations in LMNA have been shown to be responsible for other inherited
      diseases called laminopathies. Here we describe the case of a 15-year-old girl
      who was referred to our service due to diabetes mellitus and severe
      hypertriglyceridemia. Physical examination revealed generalized loss of
      subcutaneous fat, confirmed by DEXA (total body fat 8.6%). As the patient
      presented with pubertal-onset of generalized lipodystrophy and insulin
      resistance, molecular analysis of the LMNA gene was performed. We identified a
      heterozygous substitution in exon 1 (c.29C>T) predicting a p.T10I mutation. In
      summary, we describe an atypical phenotype of lipodistrophy associated with a de
      novo appearance of the p.T10I mutation in LMNA gene.

PMID- 19169478
TI  - [Absence of PRKAR1A loss of heterozygosity in laser-captured microdissected
      pigmented nodular adrenocortical tissue from a patient with Carney complex caused
      by the novel nonsense mutation p.Y21X].
AB  - OBJECTIVE: Primary pigmented nodular adrenocortical disease (PPNAD) is the main
      endocrine manifestation of Carney complex, a multiple neoplasia syndrome caused
      by PRKAR1A gene mutations. The presence of PRKAR1A loss of heterozygosity (LOH)
      in adrenocortical tumorigenesis remains controversial. The aim of the present
      study is to investigate the presence of PRKAR1A LOH in adrenocortical cells in a
      patient with Carney complex. METHODS: The LOH was investigated using a PRKAR1A
      informative intragenic marker by GeneScan software analysis in DNA obtained from
      laser-captured microdissected cells of several adrenal nodules. PATIENTS: A young
      adult male patient with Carney complex and his family were studied. RESULTS: A
      novel heterozygous mutation (p. Y21X) was identified at PRKAR1A in blood DNA of
      the male proband and his relatives. No PRKAR1A LOH was evidenced in the laser
      captured microdissected cells from PPNAD tissue by different methodologies.
      CONCLUSION: We identified a new PRKAR1A nonsense mutation and in addition we did
      not evidence PRKAR1A LOH in laser-captured nodules cells, suggesting that
      adrenocortical tumorigenesis in PPNAD may occurs apart from the second hit.

PMID- 19169479
TI  - [Novel nonsense mutation (p.Y113X) in the human growth hormone receptor gene in a
      Brazilian patient with Laron syndrome].
AB  - BACKGROUND: To date, about sixty different mutations within GH receptor (GHR)
      gene have been described in patients with GH insensitivity syndrome (GHI). In
      this report, we described a novel nonsense mutation of GHR. METHODS: The patient
      was evaluated at the age of 6 yr, for short stature associated to clinical
      phenotype of GHI. GH, IGF-1, and GHBP levels were determined. The PCR products
      from exons 2-10 were sequenced. RESULTS: The patient had high GH (26 microg/L),
      low IGF-1 (22.5 ng/ml) and undetectable GHBP levels. The sequencing of GHR exon 5
      disclosed adenine duplication at nucleotide 338 of GHR coding sequence
      (c.338dupA) in homozygous state. CONCLUSION: We described a novel mutation that
      causes a truncated GHR and a loss of receptor function due to the lack of amino
      acids comprising the transmembrane and intracellular regions of GHR protein,
      leading to GHI.

PMID- 19169480
TI  - Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a novel
      mutation in arginine-vasopressin gene in a Brazilian family.
AB  - Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a
      rare autosomal dominant disorder characterized by polyuria and polydipsia due to
      deficiency of arginine vasopressin (AVP). More than 50 mutations causing adFNDI
      have been already reported in the AVP gene. The aim of the present study is to
      analyze the AVP gene in four generations of one Brazilian kindred with adFNDI.
      The proband was a 31-year old female with huge hypotonic polyuria (10 L/day)
      dated from childhood. Molecular analysis included amplification of all exons and
      exon-intron regions of the AVP gene by PCR and direct sequencing. Sequencing
      analysis showed a novel point mutation in heterozygous: G88V (GGC>GTC). All
      affected patients presented the same mutation also in heterozygous, while it was
      absent in four normal members. We expand the repertoire of mutations in AVP
      describing the novel G88V mutation in one Brazilian kindred with adFNDI.

PMID- 19169481
TI  - Apparent mineralocorticoid excess syndrome in a Brazilian boy caused by the
      homozygous missense mutation p.R186C in the HSD11B2 gene.
AB  - The apparent mineralocorticoid excess syndrome (AME) is a rare autosomal
      recessive disorder due to the deficiency of 11beta-hydroxysteroid dehydrogenase
      type 2 enzyme (11beta-HSD2). The 11beta-HSD2 enzyme, encoded by HSD11B2 gene,
      metabolizes active cortisol in cortisone. Mutations on HSD11B2 gene affect the
      enzyme activity by leading to an excess of cortisol, which causes its
      inappropriate access to mineralocorticoid receptor. Therefore, cortisol will bind
      mineralocorticoid receptor. The human HSD11B2 gene maps to chromosome 16q22 and
      consists of five exons encoding a protein of 405 amino acids. We present here
      clinical and molecular studies on a Brazilian boy who was born pre-term after an
      oligodramnious pregnancy. He was diagnosed as having AME at the age of 26 months.
      His parents are second cousins. Molecular characterization of the HSD11B2 gene
      revealed the homozygous mutation p.R186C. The patient described here is the
      second case of HDS11B2 gene mutation reported in Brazilian patients with AME.

PMID- 19169482
TI  - Tall stature and poor breast development after estrogen replacement in a
      hypergonadotrophic hypogonadic patient with a 45,X/46,X,der(X) karyotype with
      SHOX gene overdosage.
AB  - SHOX is exclusively expressed in the developing distal limb bones of human
      embryos and in the first and second pharyngeal arches. It works as a promoter for
      linear growth and as a repressor of growth plate fusion. It was reported,
      recently, that SHOX overdosage and gonadal estrogen deficiency have led to tall
      stature due to continued growth. We report, in the present study, a female
      patient with 45,X/46,X, psu idic(X)(pter-->q21::q21-->pter) karyotype, tall
      stature, and hypergonadotrophic hypogonadism without Turner stigmas. She did not
      present breast development even after long term therapy with high estrogen doses.
      Fluorescence in situ hybridization depicted the presence of three copies of SHOX
      gene. Microsatellite studies showed paternal origin of der(X). Further studies in
      similarly affected patients will clarify if the absence of breast development,
      despite previous high-dose estrogen treatment, is associated to triple copy of
      SHOX gene.

PMID- 19169483
TI  - Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and
      gsp status as predictors of octreotide LAR responsiveness in acromegaly.
AB  - We present two acromegalic patients in which clinical and molecular data are
      discussed in regard to their ability to predict long term octreotide LAR therapy
      response. CASE REPORTS: Patient 1: female, 36 years old at diagnosis. Basal GH
      and IGF-I at diagnosis were 133 ng/mL and 181% above the upper limit of reference
      values (ULRV), respectively. Growth hormone during acute test with subcutaneous
      octreotide decreased from 133 to 13 ng/mL. Patient started on primary octreotide
      LAR therapy (20mg q28 days) and achieved biochemical parameters of disease
      control after 6 months. Molecular analysis of tumor fragments: gsp +;
      quantitative analysis of SSTR (somatostatin receptor) and DR (dopamine receptor)
      mRNA - SSTR2 23954; SSTR5 2407; DR2 total 17016 copies. Patient 2: male, 38 years
      old at diagnosis. Basal GH and IGF-I at diagnosis were 120 ng/mL and 114% ULRV,
      respectively. Patient underwent non-curative trans-sphenoidal surgery. Post
      operative GH and IGF-I were 112 ng/mL and 137% ULRV, respectively. Growth hormone
      during acute test with subcutaneous octreotide decreased from 112 to 7 ng/mL.
      Octreotide LAR therapy (20 mg q28 days) was then initiated. After 6 months of
      treatment, patient did not attain biochemical control of disease and displayed
      increased tumor volume. Molecular analysis of tumor fragments: gsp not done;
      quantitative analysis of SSTR and DR mRNA - SSTR2 416; SSTR5 3767; DR2 total 3439
      copies. In conclusion, these two cases illustrate how laboratory data can be
      conflicting as predictors of octreotide LAR responsiveness and how molecular
      analysis of tumor fragments can help explain different behaviors in clinically
      similar patients.

PMID- 19169484
TI  - Pendred syndrome in a large consanguineous Brazilian family caused by a
      homozygous mutation in the SLC26A4 gene.
AB  - Pendred Syndrome (PS) is an autossomal recessive disorder characterized by
      sensorineural deafness, goiter and iodide organification defect. The hearing loss
      is associated with inner ear abnormalities, ranging from an isolated enlarged
      vestibular aqueduct (EVA) to a typical coclear dysplasia. Mutations in the gene
      that encodes pendrin (SLC26A4), a chloride/iodide transporter, have been shown to
      be associated with PS. We describe the clinical and molecular characteristics of
      a large consanguineous family harboring a mutation in the SLC26A4 gene. The
      proband was a 26-year-old deaf Brazilian woman who presented a bulky multinodular
      goiter and hypothyroidism since puberty. Five other siblings were deaf: one
      brother had a similar phenotype, three siblings also had goiters but normal
      thyroid function tests, and one brother had only a subtle thyroid enlargement.
      Other 4 siblings had no thyroid or hearing disorder. Parents were first degree
      cousins and had normal hearing. The mother was healthy, except for subclinical
      hypothyroidism; the father was deceased. A perchlorate test in the proband showed
      a discharge of 21% of the incorporated iodide 2h after the administration of 1g
      of KClO4. Audiological examinations showed profound hearing loss in all deaf
      subjects; CT and MRI of the temporal bones showed EVA in all of them. Genomic DNA
      was isolated from whole blood, from the 6 affected and 4 unaffected siblings, the
      mother and control. The coding region of the PDS gene (exons 2-21), including
      exon/intron boundaries, were amplified by PCR and sequenced. A single base-pair
      (T) deletion at position 1197 of exon 10 was detected in homozygous state in the
      6 deaf siblings. The mother and 2 unaffected siblings were heterozygous for this
      mutation, which has been described by Everett et al. The 1197delT mutation is
      predicted to result in a frameshift and a truncated protein. The existence of PS
      phenocopies and intrafamilial phenotypic variability are well documented. The
      definite diagnosis requires molecular analysis. Our study illustrates the value
      and challenges of mutational analysis in selected patients with PS.

PMID- 19169485
TI  - A novel mutation of thyroid hormone receptor beta (I431V) impairs corepressor
      release, and induces thyroid hormone resistance syndrome.
AB  - Resistance to thyroid hormone (RTH) is a rare disorder characterized by variable
      tissue hyporesponsiveness to thyroid hormone, usually caused by mutations in the
      thyroid hormone receptor beta (TRbeta). We describe a large Brazilian family
      harboring a novel mutation affecting TRbeta gene and inducing RTH. A 14-year-old
      girl was found to have elevated free T4 and free T3 plasma concentrations in
      coexistence with unsuppressed TSH and a questionable goiter. The diagnosis of RTH
      was verified by identification of a novel mutation (I431V) in the TRbeta gene.
      Sixteen asymptomatic relatives of the proposita are also affected by the
      mutation. Functional studies showed that I431V mutation exerts dominant-negative
      effect on wild type TRbeta, mainly by impairment of ligand-dependent release of
      corepressor SMRT. The presence of this mutation reduces potency, but does not
      affect efficacy of thyroid hormone action, in accordance with the clinical
      picture of eumetabolism of the affected individuals.

PMID- 19169486
TI  - Seven-year follow-up of a juvenile female with papillary thyroid carcinoma with
      poor outcome, BRAF mutation and loss of expression of iodine-metabolizing genes.
AB  - BACKGROUND: Recent studies reported that BRAF V600E mutation, the most prevalent
      genetic event found in papillary thyroid carcinoma, is an independent poor
      prognostic marker. Additionally, it correlates with a less differentiated tumor
      stage due to reduced expression of key genes involved in iodine metabolism. We
      previously described a patient with BRAF V600E mutation in primary tumor and a
      new mutation (V600E+K601del) in the matched-lymph node metastases. In the present
      study we report an unusual clinical behavior of PTC and correlate with BRAF
      mutational status and level of expression of TSHR and NIS. METHODS: Quantitative
      PCR (qPCR) was used to evaluate the NIS and TSHR level of expression in matched
      papillary thyroid carcinoma and adjacent normal tissue. RESULTS: In this study,
      we presented a seven-year follow up of a juvenile papillary thyroid carcinoma
      patient who had an aggressive tumor harboring BRAF mutation, and failed to
      conventional therapy. We found a markedly decrease of NIS and TSHR expression in
      primary PTC compared to adjacent normal thyroid tissue. CONCLUSION: Our findings
      suggest that BRAF mutational status and decreased NIS and TSHR expression in this
      patient may reduce radioiodine uptake and lead to a negative response to
      radioiodine therapy.

PMID- 19169487
TI  - Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a homozygous 25 BP
      duplication (NT 4157-4181) at exon 5 in the CYP17 resulting in a premature stop
      codon predicted by molecular modeling.
AB  - Combined 17alpha-hydroxylase/17,20-lyase deficiency is a rare, autosomal
      recessive form of congenital adrenal hyperplasia characterized by the coexistence
      of hypertension, caused by the hyperproduction of mineralocorticoid precursors
      and DSD in males and sexual infantilism in females, due to impaired production of
      sex hormones. Several CYP17 mutations resulting in 17alpha-hydroxylase/17,20
      lyase deficiency have been reported previously. In the present study, we
      described a novel CYP17 mutation in two Brazilian sisters with primary
      amenorrhea, 46,XY karyotype, high basal levels of progesterone (3.4-4.9 ng/mL)
      and hypokalemic hypertension born to consanguineous parents. After PCR and
      automatic sequencing of CYP17 coding region, 25 bp duplication at exon 5 was
      found in the patients. This duplication started at codon 318 resulting in a
      premature stop codon at position 320 resulting in an ineffective and truncated
      protein and in accordance with the molecular modeling of P450c17. Therefore we
      expanded the repertoire of CYP17 mutations describing the largest duplication
      found in this gene in both sisters, with a clinical phenotype of combined 17alpha
      hydroxylase/17,20-lyase deficiency and emphasizes the importance of the P450c 17
      molecular modeling to predict the functional effect of these mutations.

PMID- 19169488
TI  - Recurrence of papillary thyroid cancer suspected by high anti-thyroglobulin
      antibody levels and detection of peripheral blood thyroglobulin mRNA.
AB  - The amplification of thyroglobulin (TG) mRNA in peripheral blood of patients with
      thyroid cancer has been studied for almost one decade, but its real contribution
      for diagnosis of cancer relapse has not yet been established. In the present
      paper we report the case of a patient with papillary thyroid cancer with
      undetectable stimulated serum thyrogobulin levels after thyroid ablation. Follow
      up showed the presence of high titers of anti-thyroglobulin antibodies and the
      presence of TG mRNA in a peripheral blood sample, while cervical ultrasound and
      thorax and cervical computerized tomography were negative. Reinvestigation
      confirmed lymph node metastases. Anti-TG antibodies progressively decreased after
      surgery for metastatic lymph nodes resection followed by radioiodine therapy.
      Although our recent findings show that patients with positive TG mRNA do not have
      increased risk of cancer recurrence after 24 months of follow-up, the presence of
      TG mRNA along with high anti-TG antibodies were important indicators that
      determined further extensive investigation of tumour relapse in this patient,
      since positron emission tomography scan was not available at our Institution. A
      methodological standardization that can distinguish specific from non-specific TG
      mRNA amplification might be of great interest for the follow-up of differentiated
      thyroid cancer, especially in patients with high levels of anti-TG antibodies.

PMID- 19169489
TI  - HNF1alpha mutations are present in half of clinically defined MODY patients in
      South-Brazilian individuals.
AB  - Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes
      mellitus characterized by autosomal dominant inheritance, early age of onset, and
      pancreatic beta cell dysfunction. Heterozygous mutations in at least seven genes
      can cause MODY. In the present study we investigated the relative prevalence of
      GCK (glucokinase) and HNF1alpha (hepatocyte nuclear factor 1alpha) mutations, the
      more frequent causes of MODY, in 13 South-Brazilian families with multiple cases
      of diabetes consistent with MODY. Heterozygous variants in GCK and HNF1alpha
      genes were observed respectively in one (7.7%), and six (46.2%) families. The six
      HNF1alpha variants are likely to cause diabetes in the families where they were
      observed. However, we could not ascertain whether the GCK Gly117Ser variant found
      in one family is a causal mutation. In conclusion, we have confirmed in a South
      Brazilian population that HNF1alpha mutations are a common cause of monogenic
      diabetes in adults selected with strict clinical diagnostic criteria.

PMID- 19169490
TI  - Pancreatitis as the first manifestation of multiple endocrine neoplasia type 2A.
AB  - Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant inherited
      condition that predisposes to the triad of medullary thyroid cancer (MTC),
      pheochromocytoma (Pheo), and primary hyperparathyroidism (PHT). Nearly 100% of
      MEN2A are associated with germ line mutation of the RET proto-oncogene (RET), and
      DNA-based RET genotype analysis is now considered essential for earlier
      diagnosis. The first manifestation of MEN2A is most often due to MTC, and less
      frequently to Pheo. Rarely, MEN2A is recognized during the search for PHT
      associated conditions. Most patients with primary hyperparathyroidism are
      asymptomatic, and the focus of the presentation may be the side effects of
      chronic hypercalcemia, osteoporosis, renal lithiasis, peptic ulcer disease, and
      hypertension. Hypercalcemic pancreatitis is rare, being an uncommon first
      manifestation of PHT. Here, we report on a patient who presented recurrent
      pancreatitis as the first manifestation of MEN2A. In the present case, prompt
      sequential dosage of calcium, diagnosis of PHT, and genetic analysis would have
      resulted in pancreatitis prevention and early MEN2A management.

PMID- 19169491
TI  - A molecular analysis and long-term follow-up of two siblings with severe
      congenital hypothyroidism carrying the IVS30+1G>T intronic thyroglobulin
      mutation.
AB  - OBJECTIVE: To extend the molecular analysis of the IVS30+1G>T intronic
      thyroglobulin (TG) mutation, and to report the eleven year follow-up of the
      affected patients. METHOSD: Two siblings with severe congenital hypothyroidism
      with fetal and neonatal goiter, harboring the IVS30+1G>T mutation were included.
      Nodular and non-nodular thyroid tissue specimens were collected. Specific thyroid
      genes expression was evaluated by real-timePCR and by immunohistochemistry.
      RESULTS: In non-nodular tissue specific thyroid genes mRNA were reduced when
      compared to normal thyroid sample. In the nodule, TPO and NIS expression was very
      low. Microscopic examinations showed very large follicular-lumina and swollen
      vesicles of endoplasmatic-reticulum. Strong cytoplasmatic and low follicular
      lumen TG immunostaining were detected. Intracellular NIS, membrane TPO and TSHR
      immunostaining had higher positivity in non-nodular sample. Both patients had a
      long-term adequate developmental outcome, besides one patient have been lately
      treated. CONCLUSIONS: IVS30+1G>T mutation not only lead to very enlarge
      endoplasmatic-reticulum, but also to alterations of specific thyroid genes
      expression. The clinical evolution of patients harboring these mutations
      strengthen the concept of the influence of environment, like iodine nutrition, to
      determine the final phenotypic appearance.

PMID- 19169492
TI  - Unusual occurrence of intestinal pseudo obstruction in a patient with maternally
      inherited diabetes and deafness (MIDD) and favorable outcome with coenzyme Q10.
AB  - Maternally inherited diabetes and deafness (MIDD) has been related to an A to G
      transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. This
      subtype of diabetes is characterized by maternal transmission, young age at onset
      and bilateral hearing impairment. Besides diabetes and deafness, the main
      diagnostic features, a wide range of multisystemic symptoms may be associated
      with the A3243G mutation. Organs that are most metabolically active, such as
      muscles, myocardium, retina, cochlea, kidney and brain are frequently affected.
      Gastrointestinal tract symptoms are also common in patients with mitochondrial
      disease and constipation and diarrhea are the most frequent manifestations.
      However, there are few prior reports of intestinal pseudo obstruction in MIDD
      patients. Here we report the case of a patient with MIDD associated with the
      mtDNA A3243G mutation who developed chronic intestinal pseudo obstruction, and
      the introduction of Coenzyme Q10 as adjunctive therapy led to a solution of the
      pseudo obstruction.

PMID- 19169493
TI  - Glibenclamide unresponsiveness in a Brazilian child with permanent neonatal
      diabetes mellitus and DEND syndrome due to a C166Y mutation in KCNJ11 (Kir6.2)
      gene.
AB  - Heterozygous activating mutations of KCNJ11 (Kir6.2) are the most common cause of
      permanent neonatal diabetes mellitus (PNDM) and several cases have been
      successfully treated with oral sulfonylureas. We report on the attempted transfer
      of insulin therapy to glibenclamide in a 4-year old child with PNDM and DEND
      syndrome, bearing a C166Y mutation in KCNJ11. An inpatient transition from
      subcutaneous NPH insulin (0.2 units/kg/d) to oral glibenclamide (1 mg/kg/d and
      1.5 mg/kg/d) was performed. Glucose and C-peptide responses stimulated by oral
      glucose tolerance test (OGTT), hemoglobin A1c levels, the 8-point self-measured
      blood glucose (SMBG) profile and the frequency of hypoglycemia episodes were
      analyzed, before and during treatment with glibenclamide. Neither diabetes
      control nor neurological improvements were observed. We concluded that C166Y
      mutation was associated with a form of PNDM insensitive to glibenclamide.

PMID- 19169494
TI  - Possible association between Carney complex and multiple endocrine neoplasia type
      1 phenotypes.
AB  - Carney Complex (CNC) and Multiple Endocrine Neoplasia type 1 (MEN1) are forms of
      multiple endocrine neoplasia of dominant autosomal inheritance. Diagnosis of CNC
      occurs when two major criteria (lentiginoses, primary pigmented nodular
      adrenocortical disease, cardiac and cutaneous myxomas, acromegaly, testicular
      neoplasias, thyroid cancer) are observed and/or a major criterion associated with
      a supplementary criterion (affected relative, PRKAR1A gene mutation) occurs. On
      the other hand, diagnosis for MEN1 occurs through detection of two or more tumors
      located at the pituitary gland, parathyroid and/or pancreatic cells. The present
      case describes a 55 year-old male patient, diagnosed with acromegaly, primary
      hyperparathyroidism and papillary thyroid cancer, exhibiting components that meet
      the diagnostic criteria of both conditions described. Despite the occurrence of
      only one sporadic association or the acromegaly per se being responsible for the
      papillary cancer, new molecular mechanisms may not be ruled out.

PMID- 19169495
TI  - Allele-specific PCR assay to genotype SNP rs7903146 in TCF7L2 gene for rapid
      screening of diabetes susceptibility.
AB  - OBJECTIVE: The aim of the present study is to validate a rapid and simple allele
      specific PCR that genotypes TCF7/L2 rs7903146 (C/T) polymorphism with standard
      PCR instruments. METHODS: Two forward primers with variations in their 3'
      nucleotides were designed in such a way that each was specific for one of the two
      variants. They were combined with a common reverse primer into two PCR reactions.
      Specific amplification indicates the presence of the allele. One hundred and four
      DNA samples were genotyped by this method. To evaluate the assay, the
      polymorphism spanning region of 63 DNA samples representing the three possible
      genotypes was sequenced. RESULTS: The rs7903146 allele assignments derived from
      the allele-specific PCR were in complete agreement with sequencing. CONCLUSIONS:
      The assay described here is a suitable strategy for the TCF7/L2 rs7903146 (C/T)
      genotyping also allowing rapid and reliable identification.

PMID- 19169496
TI  - Association between 894G>T endothelial nitric oxide synthase gene polymorphisms
      and metabolic syndrome.
AB  - Metabolic syndrome (MS) is a cluster of cardiovascular risk factors such as
      hypertension, dyslipidemia, obesity and type II diabetes. Here, we performed a
      case-control study analyzing the association between 894G>T endothelial nitric
      oxide synthase gene polymorphism (NOS3) and MS in 616 subjects. Genotype
      frequencies were TT= 9.3%, GG= 37.2 and TG= 53.6% and the allelic frequencies
      were T=0.36 and G= 0.64. We observed a higher TT genotype frequency in the male
      MS group than control subjects (p=0.02), independent of other variables. We found
      an association between hypertension and TT genotype in females. Our data suggests
      that 894G>T plays a significant role in the mechanistic interaction between
      metabolic risk such as hypertension and MS, although sex-related differences may
      exist.

PMID- 19169497
TI  - Prevalence of the polymorphism MTHFR A1298C and not MTHFR C677T is related to
      chromosomal aneuploidy in Brazilian Turner Syndrome patients.
AB  - BACKGROUND: Dysfunctions in the folate metabolism can result in DNA
      hypomethylation and abnormal chromosome segregation. Two common polymorphisms of
      this enzyme (C677T and A1298C) reduce its activity, but when associated with
      aneuploidy studies the results are conflicting. The objective of the present
      study is to analyze the MTHFR gene polymorphisms in women with Turner Syndrome
      and in a control group, correlating the findings to the chromosomal aneuploidy.
      METHODS: The study comprised 140 patients with Turner Syndrome, of which 36 with
      chromosome mosaicism and 104 non-mosaics, and a control group of 209 fertile and
      healthy women without a history of any offspring with aneuploidy. Polymorphisms
      C677T and A1298C were studied by RFLP-PCR and the results were statistically
      analyzed. RESULTS: The frequency of genotypes MTHFR 677CC, 677CT and 677TT in the
      patients with Turner Syndrome and chromosome mosaicism was, respectively, 58.3%,
      38.9% and 2.8%. Among the patients with non-mosaic Turner Syndrome, 47.1%
      presented genotype 677CC, 45.2% genotype 677CT, and 7.7% genotype 677TT. Among
      the 209 individuals of the control group, genotypes 677CC, 677CT and 677TT were
      found at the following frequencies: 48.3%, 42.1% and 9.6%, respectively. As for
      polymorphism A1298C, the patients with Turner Syndrome and chromosome mosaicism
      presented genotypes 1298AA, 1298AC and 1298CC at the following frequencies:
      58.3%, 27.8% and 13.9%, respectively. Among the non-mosaic Turner Syndrome
      patients, genotype 1298AA was found in 36.5%, genotype 1298AC in 39.4%, and
      genotype 1298CC in 22.1%. In the control group, genotypes 1298AA, 1298AC and
      1298CC were present at the following frequencies: 52.6%, 40.7% and 6.7%,
      respectively. CONCLUSION: No correlation was observed between the MTHFR gene
      polymorphism 677 and chromosomal aneuploidy in the Turner Syndrome patients.
      However, the MTHFR gene polymorphism at position 1298, mainly genotype 1298CC
      that reduces the enzyme efficiency, was more frequent in the group of Turner
      Syndrome patients, suggesting its involvement in mechanisms related to
      chromosomal imbalances.

PMID- 19169498
TI  - Cryptic intragenic deletion of the SHOX gene in a family with Leri-Weill
      dyschondrosteosis detected by Multiplex Ligation-Dependent Probe Amplification
      (MLPA).
AB  - LWD is associated to SHOX haploinsufficiency, in most cases, due to gene
      deletion. Generally FISH and microsatellite analysis are used to identify SHOX
      deletion. MLPA is a new method of detecting gene copy variation, allowing
      simultaneous analysis of several regions. Here we describe the presence of a SHOX
      intragenic deletion in a family with LWD, analyzed through different
      methodologies. Genomic DNA of 11 subjects from one family were studied by
      microsatellite analysis, direct sequencing and MLPA. FISH was performed in two
      affected individuals. Microsatellite analysis showed that all affected members
      shared the same haplotype suggesting the involvement of SHOX. MLPA detected an
      intragenic deletion involving exons IV-VIa, which was not detected by FISH and
      microsatellite analysis. In conclusion, the MLPA technique was proved to be the
      best solution on detecting this small deletion, it has the advantage of being
      less laborious also allowing the analysis of several regions simultaneously.

PMID- 19169499
TI  - Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in
      neonatal screening.
AB  - Steroid 21-hydroxylase deficiency (21-OHD) accounts for more than 90% of
      congenital adrenal hyperplasia. CAH newborn screening, in general, is based on 17
      hydroxyprogesterone dosage (17-OHP), however it is complicated by the fact that
      healthy preterm infants have high levels of 17-OHP resulting in false positive
      cases. We report on molecular features of a boy born pre-term (GA = 30 weeks;
      weight = 1,390 g) with elevated levels of 17-OHP (91.2 nmol/L, normal < 40) upon
      neonatal screening who was treated as having CAH up to the age of 8 months. He
      was brought to us for molecular diagnosis. Medication was gradually suspended and
      serum 17-OHP dosages mantained normal. The p.V281L mutation was found in compound
      heterozygous status with a group of nucleotide alterations located at the 3' end
      intron 4 and 5' end exon 5 corresponding to the splice site acceptor region.
      Molecular studies continued in order to exclude the possibility of a nonclassical
      21-OHD form. The group of three nucleotide changes was demonstrated to be a
      normal variant since they failed to interfere with the normal splicing process
      upon minigene studies.

PMID- 19169500
TI  - Early diagnosis of multiple endocrine neoplasia type 2B: a challenge for
      physicians.
AB  - BACKGROUND: The hereditary form of medullary thyroid carcinoma may occur isolated
      as a familial medullary thyroid carcinoma (FMTC) or as part of Multiple Endocrine
      Neoplasia 2A (MEN2A) and 2B (MEN2B). MEN2B is a rare syndrome, its phenotype may
      usually, but not always, be noted by the physician. In the infant none of the
      MEN2B characteristics are present, except by early gastrointestinal dysfunction
      caused by intestinal neuromas. When available, genetic analysis confirms the
      diagnosis and guides pre-operative evaluation and extent of surgery. Here we
      report four cases of MEN2B in which the late diagnosis had a significant impact
      in clinical evolution and, potentially, in overall survival. CASE REPORT: We
      report four cases, 2 men and 2 women, with differences in their phenotypes and
      with a late diagnosis. The first case has a history of severe gastrointestinal
      obstruction requiring a surgery intervention two days after his birth. The second
      told had nodules in the oral mucosa and constipation since childhood. The third
      case referred a history of constipation from birth until 5 months of life. The
      fourth has had a history of chronic constipation since childhood. DISCUSSION: New
      concepts have emerged since the RET oncogene was identified in 1993 as the
      responsible gene for hereditary medullary thyroid carcinoma. The majority of
      MEN2B individuals have M918T mutation in the exon 16 of RET, with a few cases
      having a mutation A883F or the association of V804M with E805K, Y806C or S904C
      mutations. The consensus classifies the RET mutation in codon 918 as of highest
      risk and recommends total thyroidectomy and central lymph node dissection until 6
      months after birth. A fast and precise diagnosis is essential to reach these
      goals. The identification of early manifestations such as intestinal
      ganglioneuromatosis and oral mucosal neuromas should prompt the physician to
      initiate an investigation for multiple endocrine neoplasia type 2B. CONCLUSION:
      The diagnosis of MEN2B is very important to allow appropriate investigation of
      associated diseases and to allow counseling and appropriate screening of
      relatives for a RET mutation. Even patients with MEN2B, which often have typical
      physical features, may not be properly recognized and be followed as a sporadic
      case. Based on this, all suspicious cases of multiple endocrine neoplasia should
      undergo a molecular genetic test.

PMID- 19169503
TI  - Note on the scientific paper "Intraocular pressure in schizophrenic patients
      treated with psychiatric medications.".

PMID- 19169504
TI  - [Relevance of Ethics Committee in Research in scientific publications].

PMID- 19169505
TI  - [Preliminary results of a computerized and stereoscopic system for in vivo
      pupillometry].
AB  - PURPOSE: We developed a digital system with accommodation capacities for
      measurement of the diameter and shape of the in vivo pupil for 10 different
      levels of illumination intensity, varying from mesopic to photopic. METHODS: An
      optical system for conjugating images from an infrared and white light
      illuminated pupil was designed and mounted using an ophthalmoscope helmet and a
      typical diving mask as support for a high-resolution and sensitivity CCD. Using
      an IBM compatible computer sequences of video in AVI format were digitized for
      several seconds at a mean rate of 30 Hz. Algorithms using principles of image
      processing were implemented for detection of the pupil edges. RESULTS: We present
      preliminary results of this system for a voluntary patient. Data for the
      horizontal (x) and vertical (y) central position and for the diameter of the
      pupil were then exported to files that could be read by typical spread sheet
      programs (Excel). CONCLUSIONS: In this manner, precise data can be obtained
      stereoscopically (for both pupils at the same time) for any patient, given that
      the accommodation process is guaranteed by using a white LED virtual mire located
      6 meters from the patient's eye. An electronic board precisely controls the level
      of illumination. We believe here developed instrument may be useful in certain
      ophthalmic practices where precise pupil geometric data are needed.

PMID- 19169506
TI  - HLA-matched living-related conjunctival limbal allograft for bilateral ocular
      surface disorders: long-term results.
AB  - PURPOSE: To evaluate the long-term outcome of HLA-matched lr-CLAL for bilateral
      ocular surface disorders. METHODS: A retrospective, non-comparative
      interventional case series study of 39 eyes of 32 patients with bilateral surface
      disorders and clinical diagnosis of limbal stem cell deficiency who underwent HLA
      matched lr-CLAL. Visual acuity (VA), ambulatory vision (> or = 20/200) and ocular
      surface stability were evaluated as main outcomes. Donor limbus was obtained from
      a sibling or a parent of the patient, after an appropriate Class I and II HLA
      match. RESULTS: One year after surgery, VA improved in 46.2%, ambulatory vision
      was achieved in 48.7% and a stable corneal surface was achieved in 84.6% of the
      eyes. At the final follow-up (mean, 48.7 +/- 30.6 months), 66.6% of the eyes that
      had gained VA one year after surgery maintained an improved VA (p=0.28), 94.7% of
      eyes that had achieved ambulatory vision one year after surgery maintained 20/200
      or better (p<0.001) and 93.9% still had a stable corneal surface (p=0.043) at the
      final follow-up. CONCLUSIONS: HLA-matched lr-CLAL can be an adequate method of
      treatment for bilateral ocular surface disorders, with a reasonable percentage of
      success of long-term results.

PMID- 19169507
TI  - [Comparison between OPD-Scan results and visual outcomes of Tecnis ZM900 and
      Restor SN60D3 diffractive multifocal intraocular lenses].
AB  - PURPOSE: Comparison of the visual performance and wavefront analysis between
      patients with Tecnis ZM900 aspheric and AcrySof ReStor SN60D3 spheric diffractive
      multifocal intraocular lenses (IOL). METHODS: This prospective comparative study
      included 78 eyes of 39 patients. The performed ophthalmologic evaluation included
      near, intermediate and distance corrected and uncorrected visual acuity, contrast
      sensitivity measurement (under photopic and mesopic conditions) and wavefront
      analysis with the OPD-Scan aberrometrer. RESULTS: Uncorrected near and distance
      visual acuity and aberrometry analysis were similar with both intraocular lenses;
      nevertheless, intermediate visual acuity and contrast sensitivity under photopic
      conditions were statistically better with Tecnis ZM900. CONCLUSION: Both studied
      intraocular lenses promoted excellent near and distance postoperative visual
      acuity, in high contrast situations. Tecnis ZM900 IOL provided good quality of
      vision with high contrast condition in low luminosity with reduction in spherical
      aberration and improvements in intermediate visual acuity when compared to Restor
      IOL.

PMID- 19169508
TI  - New comparative ultrasound biomicroscopic findings between fellow eyes of acute
      angle closure and glaucomatous eyes with narrow angle.
AB  - PURPOSE: To compare morphometric features between fellow acute primary angle
      closure (APAC) eyes and glaucomatous or suspect eyes with narrow angle (NA).
      METHODS: Fellow eyes of 30 patients with unilateral APAC and 30 with NA were
      evaluated by ultrasound biomicroscopy (UBM) under light and dark conditions. UBM
      parameters such as anterior chamber depth (ACD), angle opening distance at 250
      microm/500 microm from the scleral spur (AOD250/AOD500), trabecular ciliary
      process distance (TCPD) and iris-lens contact distance (ILCD) were measured in
      the superior (SQ) and inferior (IQ) quadrants. RESULTS: Significant differences
      between APAC fellow and NA eyes were found in ACD, P<0.001; AOD250 at SQ and IQ,
      P<0.001; AOD500 at SQ and IQ, P<0.001; TCPD light, P=0.010 and TCPD dark at SQ,
      P=0.031; and TCPD light at IQ, P=0.010. Significant differences between light and
      dark examinations of APAC fellow eyes were found in ILCD (P=0.009) at SQ and ILCD
      at IQ (P=0.006), and of NA eyes in ILCD at SQ (P=0.047) and ILCD at IQ (P<0.001).
      CONCLUSIONS: APAC fellow eyes have a more crowded anterior segment and shallower
      ACD than NA eyes. ILCD decreases in both groups when the illumination conditions
      change from light to dark.

PMID- 19169509
TI  - [Ocular coherence tomography in age-related macular degeneration patients treated
      with photodynamic therapy with verteporforin].
AB  - PURPOSE: To identify the optical coherence tomography (OCT) findings in patients
      with age-related macular degeneration (ARMD) treated with photodynamic therapy
      (PDT). STUDY DESIGN: Open, non-randomized, interventional case series. METHODS:
      ARMD patients were submitted to a complete ophthalmological examination,
      fluorescein angiography, and OCT at baseline (V0), 3, 6, 9 and 12 months (V3, V6,
      V9 and V12, respectively). PDT was carried out according to the TAP study. Visual
      acuity (VA) was measured using the logMAR ETDRS chart. The following foveal
      measurements were performed: foveal intraretinal thickness (FIRT), foveal
      choriocapillaris - RPE complex thickness (FCC-RPET) and total foveal thickness
      (TFT). The extrafoveal thicknesses measured were: extrafoveal intraretinal
      thickness (EFIRT), extrafoveal choriocapillaris - RPE complex thickness (EFCC
      RPET) and total extrafoveal thickness (TEFT). Statistical analysis was performed
      using the block variance analysis test. RESULTS: Twenty-three eyes of 23 patients
      were enrolled. This study identified nine OCT patterns: 1) thickening of the
      foveal intraretinal layers; 2) thickening of the extrafoveal intraretinal layers;
      3) thickening of the foveal choriocapillaris - RPE complex; 4) thickening of the
      extrafoveal choriocapillaris - RPE complex; 5) intraretinal fluid; 6) subretinal
      fluid; 7) subretinal pigment epithelium (RPE) fluid; 8) vitreo-retinal adhesion;
      9) foveal depression. At baseline, FIRT and TFT were 398.5 micro and 639.2 micro,
      respectively. At V12 they were 173.7 micro e 423.9 micro, respectively, and this
      change was statistical significant (p=0.008 e p=0.003, respectively). The
      variation of the other foveal and extrafoveal measurements were not statistically
      significant. Foveal depression was present at baseline in 36.4% of the eyes,
      whereas at V12 it was present in 78.3%. Subretinal fluid was present in 36.4% of
      eyes at V0 and in 8.7% at V12. VA at baseline was 0.93 and it V12 was 1.04
      (p=0,127). CONCLUSIONS: Visual acuity was stable throughout the study. Foveal
      depression was reestablished in 78.3% at V12. FIRT and TFT decreased at a
      statistical significant level, from V0 to V12.

PMID- 19169510
TI  - [Fidelity of the potential acuity meter in the postoperative visual acuity of
      cataract surgery].
AB  - PURPOSE: To evaluate the correlation between the preoperative visual acuity (VA)
      obtained by the potential acuity meter (PAM) and the postoperative VA in a
      patient submitted to cataract surgery, as well as its correlation with the
      dominant morphologic classification of the cataract. METHODS: This is a
      prospective study performed at the Hospital Monumento Study Center. Sixty-three
      eyes of 45 patients submitted to phacoemulsification with intraocular lens
      implantation were enrolled in this study and 1 eye had been excluded. Besides the
      complete examination in the preoperative period, PAM was used and its results
      were compared with the VA at the third postoperative month and correlated with
      the dominant morphologic cataract classification. The result was called
      satisfactory when the variation was equal to or less than two lines at the
      Snellen chart. We transformed the AV into logMAR for comparison with the
      literature. RESULTS: The mean age was 45.3 years with a mean VA of 0.64 logMAR by
      the PAM. At the third postoperative month, the mean best corrected visual acuity
      (BCVA) was 0.09 logMAR. The PAM overestimated the BCVA in 8 eyes (13%),
      underestimated it in 41 eyes (66%) and in 13 eyes (21%) the BCVA were the same.
      The satisfactory results regarding nuclear cataract were reduced in cases of
      higher density (1+/4 with 75.5% e 4+/4 with 33.3%) and increased in the posterior
      subcapsular cataracts (85.7%). CONCLUSION: PAM revealed an underestimation or
      maintenance of the BCVA in most cases (87%). Its fidelity was inversely
      proportional in the nuclear cataracts (1+/4 with 75.5% e 4+/4 with 33.3%) and
      higher in the posterior subcapsular cataracts.

PMID- 19169511
TI  - [Orbital space-occupying lesions: an 11-year study of cases with histopathologic
      analysis seen at Hospital das Clinicas of FMUSP].
AB  - PURPOSE: To report the incidence of orbital space-occupying lesions in an 11-year
      interval study of patients examined at the Hospital das Clinicas of FMUSP, and to
      evaluate which are the main specialties involved in the diagnosis and treatment
      of such conditions. METHODS: All cases of orbital space-occupying lesions in the
      period from 1993 to 2004 were revised. Of 924 obtained medical records, 155 were
      selected after histopathological analysis. Another 111 cases were gathered from
      the personal archives of a pathologist responsible for Ophthalmic Histopathology,
      from which 45 cases were excluded because they had already been included in the
      first source analysis. The data were analyzed and compared with the results from
      other institutions. RESULTS: Of the studied 181 orbital space-occupying lesions,
      70% were primary, 23% secondary, 6% metastatic and lymphomas, and 1% was not
      classified. The most common specialties involved ophthalmologists in 72.37% of
      all 181 cases, head and neck surgeons in 14.36%, neurosurgeons in 6.62%, and
      others in 6.62%. CONCLUSIONS: The orbital mass lesions were treated mostly by an
      expert ophthalmologist. When other specialties were included, there was a modest
      increase in secondary tumor incidence when the final result was compared with
      previous studies on this subject. Our findings indicate that the creation of a
      trustworthy register of all orbital space-occupying lesions in Brazilian
      specialized services is necessary. The multidisciplinary character of the orbital
      mass lesions is corroborated by this review.

PMID- 19169512
TI  - [Corneal Cross-linking for the treatment of keratoconus: preliminary results].
AB  - PURPOSE: To present early visual and keratometric results for corneal cross
      linking with riboflavin and UV irradiation in patients with progressive
      keratoconus. METHODS: Twenty-five eyes of twenty patients (15 males and 5
      females) with a progressive keratoconus in the previous 6 months were followed.
      Unaided visual acuity (UVA), best spectacle corrected visual acuity (BSCVA),
      spherical equivalent (SEQ), manifest cylinder, and maximal corneal curvature (max
      K) values were followed at 1, 3 and 6 months. All patients were submitted to
      corneal cross-linking using riboflavin (vitamin B2) as the photosensitizer and
      ultraviolet light (UV, wavelength 370 nm). Epithelium was removed with 20%
      alcohol, cornea was soaked with vitamin B2 for 15 min, and then irradiated with
      UV light for 30 min, after which a bandage contact lens (BCL) was placed.
      RESULTS: UVA increased after one month (from 0.15 +/- 0.15 to 0.23 +/- 0.20), and
      went on increasing at 3 and 6 months, reaching statistical significance (p=0.025
      e p=0.037, respectively). BSCVA increased from 0.41 +/- 0.27 to 0.49 +/- 0.29 at
      month six, without reaching statistical significance at any time point.
      Progression of keratoconus stopped in all patients, in contrast with progression
      in all of them in the six-month period prior to the surgery. Max K decreased by
      more than 2 D (from 53.02 +/- 8.42 to 50.88 +/- 6.05 D), SEQ less that 1 D (from 
      3.27 +/- 4.08 to -2.68 +/- 3.02 D), while refractive cylinder decreased less than
      0.5 D (from -2.29 +/- 1.77 to -1.86 +/- 0.92 D), without reaching a statistically
      significant difference. None of the eyes lost any line of BSCVA, 12 maintained
      the preoperative BSCVA, 7 gained one line, 5 gained two lines, and 1 patient
      gained three lines of BSCVA. CONCLUSIONS: Corneal cross-linking with riboflavin
      and UV light seems to be a safe (no loss of BSCVA) and effective (anatomical and
      optical properties maintained) procedure, which has shown to stop the progression
      of the keratoconus: a reduction, although not statistically significant, of the
      corneal curvature, spherical equivalent and refractive cylinder took place in
      patients where previous progression of keratoconus had been described.

PMID- 19169513
TI  - [Angioid streaks: fundoscopic analysis of 317 cases].
AB  - PURPOSE: To evaluate the presence of choroidal neovascularization (CN) and their
      sequels in patient bearing angioid streaks (AE). METHODS: Case records of
      patients assisted from 1976 to 2006 at the Instituto Suel Abujamra located in the
      city of Sao Paulo, Brazil, were analyzed retrospectively. Age, skin color;
      patient complaints at the first evaluation, visual acuity, fundoscopic aspects
      with special attention to disciform lesions to active or scarred subretinal CN
      were considered. RESULTS: Among the 317 studied patients, 163 (51.5%) were men.
      The average age was 57, with standard deviation of 12.4 years, minimum 11 and
      maximum 91 years. Regarding skin color, 209 (66.2%) were white, 91 (29.0%) were
      yellow, 11 (3.7%) were black, and 3 (1.1%) were mulatto. AE were bilateral in all
      patients; of 631 researched eyes, 348 (55.1%) had brown color AE, in 153 (24.2%)
      they were gray and in 124 (19.6%) reddish brown. Upon diagnosis, visual acuities
      measured with the Snellen chart were worse than 20/200 in 40.4% of the eyes. CN
      absence was proven in 103 (32.5%) patients. The unilateral lesions were present
      in 112 (35.3%) and bilateral lesions were present in 99 (31.2%). Regarding
      location, 242 (74.3%) were macular, 45 (13.8%) were extramacular and 38 (11.7%)
      were both macular and extramacular. CONCLUSION: AE are an important cause of
      legal blindness and can be easily bypassed in an ophthalmic routine examination
      in the absence of active or disciform neovascular lesions. The expressive number
      of these cases brings us to the importance of this study. It highlights the need
      for a meticulous fundoscopic examination in order to improve diagnoses of the
      disease and early treatment of CN.

PMID- 19169514
TI  - Effects of mitomycin C on infiltration of polymorphonuclear leukocytes after
      epithelial scrape injury in the mouse cornea.
AB  - PURPOSE: To determine whether mitomycin C (MMC) alters appearance and
      disappearance of polymorphonuclear leucocytes (PMN) in the cornea stroma, using
      an epithelial scrape injury in eye mouse model. METHODS: Twenty-mice underwent
      mechanical epithelium debridement in the central cornea using 20% ethanol. After
      the scrape, the right eye received 0.02% MMC for one minute, while the left eye
      received physiological saline. The animals were sacrificed on days 1, 2, 5, and
      14 after surgery, and corneal whole mounts were prepared for histology. PMN
      distribution was analyzed in digitized microscope images. Cell division in the
      cornea was determined by immunohistochemical detection of bromodeoxyuridine
      (BrdU), which was injected intraperitoneally before the mice were sacrificed.
      RESULTS: Epithelial scrape injury triggered infiltration of PMNs into the corneal
      stroma. An analysis of PMN distribution revealed that there was no difference
      between eyes treated with and without MMC at all time points. BrdU labeling
      showed that 0.02% MMC for one minute blocked keratocyte proliferation completely.
      CONCLUSION: MMC treatment regimen, which is common in clinical practice, inhibits
      keratocyte proliferation during wound healing, but when used at 0.02% for one
      minute, it does not affect PMN infiltration into the corneal stroma, and
      subsequent movement toward the injury site, or the disappearance of PMNs from the
      stroma, in the mouse epithelial injury model.

PMID- 19169515
TI  - [Molecular detection of herpes simplex virus by polymerase chain reaction in
      patients with typical and atypical herpetic keratitis].
AB  - PURPOSE: To evaluate patients with clinically typical and atypical herpetic
      keratitis (HK) by means of polymerase chain reaction (PCR) as compared with the
      clinical diagnosis. METHODS: PCR in 28 patients with clinical symptoms of typical
      and atypical HK was performed. RESULTS: PCR was positive in 57.14% (n=16) of the
      total cases (n=28). The test was positive in 60.0% (n=12) of the 20 typical HK
      cases. For epithelial HK, the test was positive in 69.23% (n=9), and 77.78% (n=7)
      only for dendritic injuries. Atypical HK presented a positive test in 50% (n=4)
      of eight cases. CONCLUSION: Clinical typical picture of HK had a good correlation
      with the positive result of PCR, mainly for epithelial injury of the dendritic
      type. However, 50% of the patients with atypical HK presented positive PCR. This
      result showed that PCR test can provide an effective HK diagnosis. In the stromal
      case of HK, PCR was a useful technique to identify HSV virus.

PMID- 19169517
TI  - Visual control in children with developmental dyslexia.
AB  - PURPOSE: To assess binocular control in children with dyslexia. METHODS: Cross
      sectional study with 26 children who were submitted to a set of ophthalmologic
      and visual tests. RESULTS: In the dyslexic children less eye movement control in
      voluntary convergence and unstable binocular fixation was observed. CONCLUSION:
      The results support the hypothesis that developmental dyslexia might present
      deficits which involve the magnocellular pathway and a part of the posterior
      cortical attentional network.

PMID- 19169516
TI  - [Decrease of upper eyelid levator muscle function after involutional ptosis and
      dermatochalasis surgery].
AB  - PURPOSE: To evaluate the differences between upper eyelid levator muscle function
      (UELMF), margin reflex distance (MDR1), and eyelid crease height (ECH) before and
      after ptosis and dermatochalasis surgery. METHODS: Forty-four patients with
      blepharoptosis and dermatochalasis were enrolled. INTERVENTION: An exploration of
      the levator tendon (LT) during a blepharoplasty procedure in patients with
      blepharoptosis and dermatochalasis and in case of its disinsertion, the tendon
      was reattached to the tarsus. Measured outcome: The differences between UELMF,
      MDR1, ECH before and after surgery were evaluated bilaterally. Dependency between
      both eyes was corrected by generalized estimating equations. Pearson correlation
      was used to evaluate the dependency of the two eyes regarding UELMF, MDR1 and
      ECH. RESULTS: There was a statistical significant difference between the measures
      of UELMF before and after surgery with excursion decreasing by a mean value of
      1.1 mm after the procedure (P<0.001). Measures of MDR1 showed an increase by a
      mean of 1.6 mm and ECH decreased by a mean of 3.97 mm (P<0.001). We found a
      significant correlation between both eyes for all analyzed eyelid variables, both
      before and after surgery. Correlation before surgery was stronger for the group
      without previous surgery. The same results for correlation were found for the
      amount of disinsertion (P>0.001). CONCLUSIONS: Upper eyelid levator muscle
      function decreases after ptosis surgery.

PMID- 19169518
TI  - [Visual quality after custom versus standard LASIK retreatment].
AB  - PURPOSE: To evaluate visual quality after wavefront-guided LASIK versus standard
      LASIK in retreatment of primary LASIK for myopia and myopic astigmatism. METHODS:
      A prospective study was performed with paired eye control of 74 eyes with LASIK
      retreatment. Each patient underwent retreatment using custom ablation (Zyoptix,
      Bausch & Lomb) in 1 eye and standard ablation LASIK (PlanoScan, Bausch & Lomb) in
      the contralateral eye. A complete ophthalmologic examination was performed,
      including evaluation of glare test and contrast sensitivity test, with a follow
      up of 6 months. RESULTS: Zyoptix eyes showed better results of glare test and
      contrast sensitivity test than the contralateral eyes. CONCLUSIONS: Wavefront
      guided LASIK produces better visual quality than standard LASIK in the
      retreatment of refractive errors after primary LASIK.

PMID- 19169519
TI  - [Analysis of the life quality of infectious and non-infectious patients with
      uveitis using the NEI-VFQ-25 questionnaire].
AB  - PURPOSE: To evaluate the life quality of patients with infectious and non
      infectious uveitis evaluated at the uveitis service of the Hospital Universitario
      Clementino Fraga Filho-UFRJ, using the NEI-VFQ-25 questionnaire in order to
      clarify the importance of uveitis diagnosis and treatment as well as its
      consequences to visual and social functions of the patients. METHODS: Prospective
      study of 30 patients with uveitis, who were divided into two groups according to
      the etiology, infectious and non-infectious, with the NEI-VFQ-25 form that
      evaluates the life quality regarding general and visual health which was applied
      twice to each patient. RESULTS: The main cause of infectious uveitis was
      toxoplasmosis, and of the non-infectious was Vogt-Koyanagi-Harada syndrome.
      Concerning quality of life, general health is better in the infectious uveitis
      group, but ocular health is regular in both groups. Although visual deficit does
      not cause great disturbances and social restrictions, both groups show important
      emotional alteration, but in the non-infectious group this alteration causes a
      higher dependence level regarding daily activities. CONCLUSION: The greater
      social dependence as well as that regarding performance of daily activities in
      the uveitis group of non-infectious cause is explained by the chronic and
      relapsing mode of these affections, which turns life quality lower if compared to
      the other group.

PMID- 19169520
TI  - [Biopsychosocial profile of patients with anophthalmia in the south of Minas
      Gerais - Brazil].
AB  - PURPOSE: To evaluate the biopsychosocial profile of patients with anophthalmia,
      with emphasis on the psychological and functional impact of eye loss and the
      social reintegration of this population. METHODS: Prospective analyses of 84
      patients (50 males and 34 females), rehabilitated or in the rehabilitation
      process with ocular prostheses were interviewed by means of a questionnaire with
      dimensions involving the etiology of the ocular defect, degree of adaptation to
      the ocular prosthesis, and impact on professional, family and social activities.
      RESULT: The right eye was affected in 45.2% of the patients, the left eye in
      51.2%, and the rest of the patients had bilateral anophthalmia. Difficulty in
      adapting to monocular vision was reported by 47.6% of the patients. The main
      causes of anophthalmia in males were eye injuries due to accidents (54%), and, in
      females, acquired diseases (38.2%). For the total studied population, the eye
      loss occurred at a mean of 20.5 +/- 18.41 years, and the elapsed time until the
      first rehabilitation with ocular prosthesis was of 8.6 +/- 13.10 years. Most
      patients (66.1%) reported satisfaction and good adaptation to the prosthesis.
      Feelings of sadness, shame and shyness were frequently reported. CONCLUSION:
      Anophtalmic patients often exhibit psychic and/or functional disorders which
      hinder their social, professional and family readaptation, and this is aggravated
      by both economic factors and lack of public services that provide rehabilitative
      treatment. Public information campaigns could also be useful to prevent causes
      that lead to ocular loss.

PMID- 19169521
TI  - Effect of topical 0.5% povidone-iodine compared to 5% natamycin in fungal
      keratitis caused by Fusarium solani in a rabbit model: a pilot study.
AB  - PURPOSE: To evaluate the efficacy of topical administration of 0.5% povidone
      iodine in experimental Fusarium solani keratitis in rabbits. METHODS: Fungal
      keratitis caused by Fusarium solani was induced in the right eye of 24 New
      Zealand rabbits. The rabbits were randomly divided into 3 different treatment
      groups: Group I (povidone-iodine) - treated with topical 0.5% povidone-iodine;
      Group II (natamycin) - treated with topical 5% natamycin; and Group III (control)
      - treated with topical saline solution. In all groups the rabbits were treated
      for three days and then sacrificed. The corneas were excised, macerated and
      immersed in 10 mL BHI. Culture samples were plated daily on Sabouraud's agar for
      7 days, and the number of colony-forming units (CFU) was counted. The rabbits
      were clinically evaluated during the treatment period. RESULTS: The povidone
      iodine and natamycin groups demonstrated better efficacy than the control group
      based on the number of rabbits with no colonies growing. However, there were no
      statistically significant differences between the three groups when the number of
      CFU was analyzed (p>0.05). CONCLUSIONS: Our study demonstrates important
      methodological considerations in the use of in vivo animal models for the testing
      of antifungal agents. Using this sample size and methodology of counting CFU,
      topical 0.5% povidone-iodine demonstrated no benefit in the treatment of
      experimental Fusarium solani when compared with topical 5% natamycin.

PMID- 19169522
TI  - [An unusual orbital metastatic lesion: the only finding in a case of
      hepatocellular carcinoma: case report].
AB  - Orbital metastasis of hepatocellular carcinoma is rare. We report an unusual
      orbital metastatic lesion as the only finding in a case of hepatocellular
      carcinoma. A 57-year-old man presented with a 6-month history of orbital painful
      right orbital mass, associated with proptosis. Computed tomography of the orbits
      showed an orbital soft tissue mass leading to bone erosion and intracranial
      invasion. Computed tomography of the abdomen showed a focal perfusion abnormality
      in the left lobe of the liver. Incisional biopsy was performed and the
      histopathologic examination of the specimen confirmed the diagnosis. The patient
      died 15 months after the initial presentation. COMENTS: This is a rare case of
      orbital metastasis of hepatocellular carcinoma. There was no another metastatic
      lesion and the patient reported only ophthalmological symptoms.

PMID- 19169523
TI  - [Aneurysmal bone cyst of the orbit - a clinicopathological study: case report].
AB  - Aneurysmal bone cyst of the orbit is a rare disease that usually affects young
      patients and is caused by osseous hemodynamic alterations. We report a case of
      aneurysmal bone cyst of the orbit, referred to us as a dermoid cyst, discussing
      its clinical and histopathological aspects.

PMID- 19169524
TI  - [Primary peripheral primitive neuroectodermal tumour of the orbit: case report].
AB  - The authors present a case of primary peripheral primitive neuroectodermal tumor
      of the orbit in a 10-month-old girl, which is the first case in the Brazilian
      literature. Clinical, radiologic and histopathologic features are discussed. The
      diagnosis was confirmed by immunohistochemical analysis which is essential to the
      diagnosis of small round cell tumors in the orbit.

PMID- 19169525
TI  - Surgical treatment of macular detachment secondary to congenital pit of the optic
      disc: case report.
AB  - The authors describe a patient with macular detachment in the right eye,
      secondary to congenital pit of the optic disc, submitted to vitrectomy, drainage
      of the subretinal fluid, perfluorocarbon, endolaser and perfluoropropane gas
      (C3F8). A sample of the vitreous humor was taken for comparative analysis with
      the subretinal fluid. Results of retinography, optical coherence tomography, and
      illustrations of the surgical procedure are presented. Optical coherence
      tomography revealed the detachment resolved 6 months after surgery. Visual acuity
      improved from 20/400 to 20/30. This surgical technique can lead to successful
      reattachment of the macula and improvement of central vision. Additionally, a
      qualitative and comparative analysis showed a similar biochemical composition of
      the subretinal fluid and the vitreous. Despite technical limitations, this
      analysis can confirm the pathophysiology of the disease, suggesting that the
      subretinal fluid may originate from the vitreous cavity in macular detachment
      secondary to congenital pit of the optic disc.

PMID- 19169526
TI  - [Juvenile retinoschisis: case report].
AB  - We report a 30-year-old patient presenting a non-conclusive diagnosis of low
      progressive visual acuity for 8 years. A cystoid maculopathy (stellate striation)
      was observed in both eyes after a complete ophthalmologic examination performed
      in the emergency ward at the Clinica de Olhos da Sanata Casa de Belo Horizonte.
      The absence of contrast leakage in the foveal region identified by fluorescein
      angiography and the presence of cysts and increase of foveal thickness in optical
      coherence tomography suggested juvenile retinoschisis which could be confirmed
      through electroretinogram.

PMID- 19169527
TI  - [Lichen planus leading to bilateral cicatrizing keratoconjunctivitis: case
      report].
AB  - To describe a case of bilateral cicatrizing keratoconjunctivitis in a patient
      with lichen planus and review the literature. Conjunctiva cicatrization with
      symblepharon formation, dry eye, corneal infiltration and neovascularization and
      thinning were the most observed prominent signs. Diagnosis was based on clinical
      findings and biopsy, after exclusion of typical causes of cicatricial
      keratoconjunctivitis.

PMID- 19169528
TI  - Sympathetic ophthalmia - histopathological correlation with fluorescein and
      indocyanine green angiography: case report.
AB  - This study correlates fluorescein angiography (FA) and indocyanine green
      angiography (ICGA) to histopathologic findings in a patient with sympathetic
      ophthalmia. A male with a perforated trauma in right eye presented after two
      months a decrease in visual acuity of the left eye. FA and ICGA were performed
      and the images were correlated with the histopathologic findings of the
      enucleated eye; FA showed background areas of homogeneous hypofluorescence in the
      arterial and venous phases, as well as areas of granular progressive
      hyperfluorescence and leakage from the optic disc. ICGA showed areas of
      hypofluorescence in the early and intermediate phases of the examination, which
      persisted until the late phase. During the early phase, there was also diffuse
      hypofluorescence caused by blockage that allowed observation of areas of partial
      choroidal circulation. The histopathology of the enucleated right eye showed
      diffuse choriocapillaris edema and inflammation of the choroids, focal areas of
      hyperplasia of the retinal pigment epithelium (RPE) as well as foci of
      epithelioid cells located between the choroid and the RPE. Furthermore,
      lymphocytic infiltration of the episcleral veins and retinal detachment were
      present. The hyperfluorescence observed on FA was correlated to retinal
      detachment and optic nerve inflammation. The hypofluorescence noted on FA and
      ICGA corresponded to the presence of blocking inflammatory cells (Dalen-Fuchs
      like nodules) and to diffuse choriocapillaris edema.

PMID- 19169529
TI  - Intermediate uveitis complicated by choroidal granuloma following subretinal
      neovascular membrane: case reports.
AB  - Choroidal neovascularization is a very rare complication in intermediate uveitis.
      A 27-year-old female patient diagnosed with intermediate uveitis two years ago.
      She presented with 20/200 visual acuity, snowballs, snowbanks, and macular
      cystoid edema in the right eye observed by fluorescein and optical coherence
      tomography (OCT). Photocoagulation was performed in the inferior peripheral
      retina in both eyes. The patient refused to undergo the prescribed clinical
      treatment. She returned twelve months later presenting with count fingers visual
      acuity, dry retina and subretinal macular pigmented granuloma observed on OCT. A
      15-year-old female patient with decreased visual acuity of 20/400 in the right
      eye for eight days. She presented with bilateral vasculitis and papilitis, in the
      right eye, hemorrhage and extramacular subretinal neovascular membrane were
      observed on fluorescein and OCT. She was treated with 40 mg prednisone and
      intravitreous injection of 1.25 mg bevacizumab. Five months later she presented
      with 20/50 visual acuity, and extramacular granuloma observed on OCT. The
      formation of subretinal granuloma in intermediate uveitis is a possibility when
      complicated by subretinal neovascular membrane.

PMID- 19169530
TI  - [Adverse effects associated with facial application of botulinum toxin: a
      systematic review with meta-analysis].
AB  - PURPOSE: To estimate the occurrence of adverse effects associated with the use of
      botulinum toxin by performing a systematic review and meta-analysis. METHODS: A
      systematic literature search of MEDLINE and Cochrane Library was conducted until
      September 2007. The occurrence of the adverse effects was estimated of the
      relative frequency for case report and of the relative risk for randomized
      trials. Heterogeneity was evaluated with the Q test and I(2) index. Egger's
      significance test was used to identify the publication bias. Sensitivity analysis
      was performed to evaluate the effect of the publication biases. RESULTS: Eight
      randomized trials and thirteen case reports filled the inclusion criteria. In the
      systematic review of case reports, 1,003 subjects were studied and 182 (18.14%)
      showed adverse effects. Eyelid ptosis was the most frequent adverse effect,
      presenting in 34 (3.39%) patients of the case reports. In the meta-analysis of
      randomized trials, the overall relative risk for adverse effects as headache,
      eyelid ptosis, local reaction and infection was respectively: 1.07, 3.25, 0.99
      and 0.94. For all comparisons, P values were greater than 0.05. CONCLUSION:
      Ptosis was the most frequent adverse effect and showed the higher relative risk
      associated with botulinum toxin. It is necessary to perform a pattern of adverse
      effects related for better understanding the relationship between adverse effects
      and use of botulinum toxin.

PMID- 19169531
TI  - [Technique of intravitreal drug injection for therapy of vitreoretinal diseases].
AB  - Intravitreal injections are the standard technique applied in the treatment of
      some vitreoretinal diseases. In this paper the technique and complications of
      intravitreal injections are presented. In summary, the procedure involves various
      consecutive steps. Initially, days before the treatment topical antibiotics and
      acetazolamide may be prescribed for reduction of the ocular flora and intraocular
      pressure. Before the injection, the pupil should be dilated and topical
      anesthesia should be achieved. Injection shall be performed in the operating room
      under sterile conditions, the surgeon should wear surgical gloves and mask. The
      eye is then exposed with sterile blepharostat and sterile-drape thereby providing
      protection of the needle against the contact with contaminated lashes and lids.
      Injection is done 3.5 mm from the limbus through the pars plana. The needle
      should be inserted up to 6 mm into the vitreous cavity. Immediately after
      injection the patient must be examined by indirect ophthalmoscopy to verify
      central artery perfusion and complications as vitreous hemorrhage. Visual acuity
      better than light perception should be detected right after injection. If
      persistent central retinal artery occlusion is diagnosed, anterior chamber
      paracentesis should be performed. The patient may be discharged with an occlusive
      patch. Examination at the first postoperative day should exclude various
      complications such as endophthalmitis, and topical steroid and antibiotics should
      be prescribed for 7 days. Some complications encountered after intravitreal
      injections include retinal detachment, vitreous hemorrhage, cataract, uveitis,
      ocular hypertension, or endophthalmitis.

PMID- 19169532
TI  - [I read very carefully and reinforced interest the article "Bilateral Brown's
      syndrome in a mother and her son: case report"].

PMID- 19169533
TI  - [Acta Cirurgica Brasileira: from 2001 to 2005].

PMID- 19169534
TI  - The influence of estrogen on liver regeneration: an experimental study in rats.
AB  - PURPOSE: To recognize the regenerative capacity influenced by the administration
      of estradiol. METHODS: 42 female Wistar rats were used, divided into two groups,
      the control and the experiment group. A resection of approximately 70% of the
      liver was made in the liver of these animals. The control group received an
      intramuscular injection of one ml of peanut oil. The experiment group were given
      estradiol hexahydrobenzoate (50 microg) diluted in one ml of peanut oil.
      Calibrations were done after 36 hours and 7 days, using three methods: the
      formula of Kwon et al.21, to recognize gain in volume, counting of the mitosis
      figures in five fields and the percentage of positive PCNA nuclei. RESULTS: Gain
      in volume (mass) was similar in both groups after 36 hours (p=0.1873) and higher
      in the experiment groups after seven days (p=0.0447). Microscopy showed a similar
      number of mitosis figures after 36 hours (p=0.3528) and a tendency to be higher
      in the experiment group after 7 days (p=0.0883). The average of positive PCNA
      nuclei was higher in the experiment group both after 36 hours (p=0.0009) and 7
      days (p=0.0000). CONCLUSION: The estradiol hexahydrobenzoate improved liver
      regeneration in rats submitted to a 70% hepatectomy.

PMID- 19169535
TI  - Evaluation of low intensity laser's action on silicone mammary implant
      pseudocapsules in rats.
AB  - PURPOSE: To evaluate the effect of low intensity laser on the pseudocapsule
      contraction that occurs around silicone implants. METHODS: 60 male rats divided
      in two experimental groups received a silicone implant in the subcutaneous of the
      dorsal region. Group I: animals received implants in the subcutaneous dorsal
      region and did not receive any treatment; Group II: animals received seven
      irradiation sessions with low intensity laser after they had received
      subcutaneous implants. Thirty, 60 and 180 days after the surgery, tonometric
      evaluation of the implants was conducted. After that, the animals were
      sacrificed, study material was removed and prepared for histological examination.
      The thickness of the pseudocapsule and the inflammatory reaction were
      morphometrically quantified. Data obtained were statistically analyzed using the
      Variance method, and Tukey's Test(P<0.0 5). RESULTS: Group II animals had
      significant lower pressure. The histological study did not show a significant
      difference between the groups, but only a higher number of swollen vessels in
      Group II. The thickness of pseudocapsule around Group II's implants lower than in
      Group I. CONCLUSION: The low intensity laser modify tissue's reparation process
      around the implants suggesting it may be useful to model contractures that are
      formed around silicone implants.

PMID- 19169537
TI  - Fibroplasia after polypropylene mesh implantation for abdominal wall hernia
      repair in rats.
AB  - PURPOSE: This study assessed the collagen deposition and correlated it with local
      inflammatory responses to evaluate the length of time required for fibroplasia
      when polypropylene meshes are used to repair incisional abdominal wall hernias in
      rats. METHODS: Thirty-six male Wistar rats underwent longitudinal resection of a
      peritoneal and musculoaponeurotic tissue segment (3x2 cm) of the abdominal wall
      followed by defect reconstruction with polypropylene mesh bridging over
      aponeurosis. The animals were divided into 6 groups according to the time points
      for the analysis of fibroplasia: 1, 2, 3, 7, 21 and 30 days post-implantation.
      Animals were sacrificed at each time point, and the site where the polypropylene
      mesh was implanted was evaluated histologically to assess inflammatory response
      and percentage of collagen using computer-assisted videomorphometry. RESULTS:
      Total collagen was found at the mesh site on the 3rd day post-implantation, and
      increased progressively on all subsequent days up to the 21st day, when it
      reached its highest percentage (p<0.001). Type III collagen increased
      progressively from the 3rd to the 21st days, when it reached its highest
      percentage (p<0.001); on the 30th day, it decreased significantly (p>0.001). Type
      I collagen was first found between the 7th and 21st days; it reached its highest
      percentage on the 21st day and then remained stable until the 30th day. The type
      I to type III collagen ratio increased significantly and progressively up to the
      30th day (p<0.001). Neutrophils were found at the mesh site from the 1st to the
      21st day post-implantation. Macrophages, giant cells and lymphocytes were seen on
      the 2nd day. Thirty days after mesh implantation, neutrophils disappeared, but
      the percentages of macrophages, giant cells and lymphocytes remained stable
      (p<0.001). CONCLUSIONS: This study showed that total collagen was first seen on
      the 3rd day post-implantation, with a higher percentage of type I collagen at the
      last observational time point. The prolonged healing inflammatory response and
      the persistence of chronic inflammation surrounding to the mesh did not affect
      the length of time required for fibroplasia.

PMID- 19169536
TI  - Comparative study in swines' vocal cords healing after excision of fragment with
      CO2 laser with mitomycin and 5-fluorouracil postoperative topical application.
AB  - PURPOSE: To evaluate the deposition of collagen fibers at pig's vocal folds after
      topical use of mitomycin or 5-fluorouracil, when partial exeresis of mucosa layer
      had been promoted by CO2 laser. METHODS: There were used 18 Larger white pigs
      which were anesthetized and submitted to mucosa fragment's exeresis, bilaterally,
      at its free border. The animals were divided into 3 groups, each one with 6
      animals: control group, without topical drug application; mitomycin group; and 5
      fluorouracil group. After 30 days, the animals were subjected to euthanasia, and
      samples of the vocal folds were collected and stained by picrosirius red
      technique with polarization for quantification of total collagen deposition.
      RESULTS: In control group, the mean rate of right vocal fold's collagen
      deposition at submucosa consisted in a 3428.66 micrometers area. There was found
      an area whose size had, in average, 2196.36 micrometers, in mitomycin group, and
      2269.19 micrometers, in 5-fluorouracil group. CONCLUSION: Mitomycin and 5
      fluorouracil had promoted beneficial change in vocal fold's cicatrization with
      less collagen deposition, but there was no significant statistically difference
      when they were compared between themselves.

PMID- 19169538
TI  - The oophorectomy effect on Walker 256 tumor inoculated into the vagina and
      uterine cervix of female rats.
AB  - PURPOSE: Verify the effect of oophorectomy on the evolution of the Walker 256
      tumor inoculated into the vagina and cervix of female rats. METHODS: Ten Wistar,
      female rats were used, distributed into two groups with 05 animals each: Tumor
      group (TG): Rats inoculated with Walker 256 tumor; Oophorectomy group (OG):
      oophorectomized rats inoculated with Walker 256 tumor. The day before the tumor
      vaginal inoculation, acetic acid was inoculated into the vaginas of both groups
      of rats; the following day, the vaginal walls were scarified with an endocervix
      brush, and then Walker 256 tumor was inoculated. After 12 days, the tumor was
      removed together with the vagina and uterine horns for macro and microscopic
      analyses. The data were submitted to statistical analyses. RESULTS: There was no
      statistical difference between the two groups; however it was observed that the
      behavior of tumor growth on the OG group presented greater invasion, compromising
      the uterine horns. CONCLUSION: The results of the study on the GO group presented
      a macroscopic behavior different from the TG group, however, both of them
      presented similar development in terms of tumor mass.

PMID- 19169539
TI  - Fibrin adhesive and the vaginal vault synthesis on female rabbits abdominal
      hysterectomies.
AB  - PURPOSE: To investigate the effectiveness of fibrin glue in comparison with
      polyglycolic acid suture to promote the closure of rabbit's vaginal vault, after
      abdominal hysterectomy. METHODS: Twenty female, adults, New Zealand rabbits, were
      submitted to abdominal hysterectomy and randomly distributed to polyglycolic acid
      suture (G-PA / n=10) or fibrin glue closure of vaginal vault (G-FG / n=10).
      Radiograph study allowed identifying vault vaginal suture disrupter or fistulas
      to urinary bladder or rectum. Videovaginoscopy study allowed identifying the
      presence of cellulites, abscess formation, tissue granulation or granuloma.
      Vaginal cuff burst test allowed to identify by the escape of air bubbles and
      rupture pression record. Histological sections stained with Picrosirius red
      allowed the measure of fibrous tissue healing. RESULTS: The videovaginoscopy
      identified a significant difference (Fisher Test p<0.3142) of granulation tissue
      in the animals of G-PA (40%) in comparison with the G-FG (20%). The gross
      inspection showed the same relation in the granulation tissue occurrence (Fisher
      test p< 0.1749) with G-PA (50%) and G-FB (20%). The visceral adhesion to the
      vaginal vault wound was statistical significant (Fisher test p< 0.1749) with G-PA
      (50%) and G-FG (20%). The pressure of rupture (mm Hg) of the burst test was
      similar (p<0.0421) in the animals of G-PA (61.5+/-19.3) and G-FG (72.5+/-21.9).
      The collagen matrix of vault wound healing was similar (p< 0.0231) between the G
      PA (31.63+/-15) and the G-FG (23.2+/-13.2). CONCLUSION: The vaginal vault closure
      using the fibrin glue is a safe and reliable procedure after abdominal
      hysterectomy in female rabbit model.

PMID- 19169540
TI  - Assessment of serum enzymatic markers of cardiomyocytes injury in female dogs
      submitted to ketamine S(+), atropin and xylazine association.
AB  - PURPOSE: To assessment of the aspartate aminotransferase (AST), creatine kinase
      (CK) and creatine kinase isoenzyme fraction MB (CK-MB) serum activity in female
      dogs anesthetized with ketamine S (+), atropine and xylazine in several
      associations. METHODS: Twenty three healthy female dogs randomly distributed in
      four groups named as GI (n=6), GII (n=6), GIII (n=6) and GIV (n=5) were treated
      respectively with atropine and ketamine S(+) (0.04 mg/kg; 10 mg/kg); ketamine
      S(+) (10 mg/kg); atropine, xylazine and ketamine S(+) (0.04 mg/kg; 1.1 mg/kg; 10
      mg/kg) and xylazine and ketamine S(+) (1.1 mg/kg; 10 mg/kg). AST, CK and CK-MB
      serum activity measurement before pre-medication (M0) and one, two, three, six,
      12, 24, 36 hours after. RESULTS: There was no significant change in AST, CK e CK
      MB serum activity among groups. However, CK serum activity in relation to moments
      within the groups was increased in all groups over the time in spite of
      treatment, except GI. In relation to CK-MB activity, in the moments within the
      group, it was observed an increase compared to baseline in all groups.
      CONCLUSION: Creatine kinase and creatine kinase fraction MB isoenzyme showed
      changes in their mean values remained higher than baseline for a longer time in
      GIII and GIV.

PMID- 19169541
TI  - Arterial diameter of the celiac trunk and its branches. Anatomical study.
AB  - PURPOSE: Despite the fact that anatomical variations of the celiac trunk are well
      explored in the literature, information on these vessels diameters is scanty. The
      aims of the present study were to describe the arterial diameters of the celiac
      trunk and its main branches, and to investigate if these diameters are altered in
      those cases presenting anatomical variations of these vessels. METHODS: Twenty
      one formalin fixed adult male cadavers were appropriately dissected for the
      celiac trunk identification and arterial diameter measurements. Arteries measured
      included the celiac trunk and its main branches (splenic artery, left gastric
      artery and common hepatic artery), as the proper hepatic artery, right gastric
      artery, the left and right hepatic arteries and the gastroduodenal artery.
      RESULTS: From the 21 cadavers, 6 presented anatomical variations of, at least,
      one of the above mentioned branches. The average arterial diameter comparisons
      between groups (normal and variable) clearly showed smaller diameters for
      variable vessels, but with no significant difference. CONCLUSION: Our data
      indicates the possibility of a diameter reduction of the celiac trunk main
      branches in the presence of anatomical variations. This should be taken into
      account on the selection for the liver transplantation donors.

PMID- 19169542
TI  - Histamine iontophoresis on the viability of random skin flap in rats.
AB  - PURPOSE: To evaluate the effects of the histamine iontophoresis on the random
      skin flap viability in rats. METHODS: Sixty adult male Wistar rats were used. A
      cranially-based dorsal skin flap measuring 10 x 4 cm was raised and a plastic
      barrier was placed between the flap and its bed. After the surgical procedure,
      the animals were randomized into four groups (G1-G4) (n=15 each group) as
      follows: G1 (control)--sham electrical stimulation, G2 (electrical stimulation)-
      direct current electrical stimulation, G3 (histamine)--histamine and sham
      electrical stimulation, and G4 (histamine iontophoresis)--transdermal
      iontophoresis of histamine. In all groups the procedures were performed
      immediately after the surgery and on the two subsequent days. The percentage of
      flap necrosis was measured on the seventh postoperative day. RESULTS: The mean
      and the respective standard deviation of the percentage of flap necrosis areas
      were as follows: G1 (control) - 47.87 +/- 9.13%, G2 - 51.49 +/- 8.19%, G3 - 46.33
      +/- 8.32% and G4 - 30.82 +/- 11.25%. The G4 group presented a significantly
      smaller amount of flap necrosis when compared to the other groups (p<0.001).
      CONCLUSION: The topical administration of the histamine by iontophoresis was
      effective to increase the viability of the random skin flaps in rats.

PMID- 19169543
TI  - Postconditioning ameliorates lipid peroxidation in liver ischemia-reperfusion
      injury in rats.
AB  - PURPOSE: Liver ischemia-reperfusion injury is a phenomenon presents in events
      like liver resections and transplantation. The restoration of blood flow may
      leads to local and systemic injury. Several techniques have been developed in
      order to avoid or ameliorate ischemia-reperfusion injury in clinical situations.
      The application of a stutter reperfusion after the ischemic event
      (postconditioning) could alters the hydrodynamics and stimulates endogenous
      mechanisms that attenuate the reperfusion injury. The present study was designed
      to evaluate the potential protective effect of postconditioning in a model of
      ischemia-reperfusion in rats. METHODS: Hepatic anterior pedicle of median and
      left anterolateral segments were exposed and clamped for 1 hour. Two hours later,
      clamp was released in two different ways: Control Group (n=7): clamp was release
      straightforward; Postconditioning Group (n=7): clamp was released intermittently.
      Lipid peroxidation (malondialdehyde) and expression of the glutathione-s
      transferase-alpha-3 gene were studied. RESULTS: Lipid peroxidation was
      significantly decreased in ischemic and non-ischemic liver by postconditioning.
      GST- alpha3 gene was overexpressed in post-conditioned group, but not
      significantly. CONCLUSION: Postconditioning induced hepatoprotection by reducing
      lipid peroxidation in the ischemic and non-ischemic liver.

PMID- 19169544
TI  - Anastomotic healing in ileum and colon of alloxan-induced diabetic rats.
AB  - PURPOSE: To investigate if diabetes mellitus may alter breaking strength (BS) and
      collagen content in ileum and colon anastomoses in rats. METHODS: Three-hundred
      Wistar rats were randomly assigned to 5 experimental groups, 60 per group: normal
      controls surgically manipulated (G1); normal controls submitted to ileum (G2) and
      colon (G3) anastomotic construction; diabetic rats submitted to ileum (G4) and
      colon (G5) anastomotic construction. Each group was further divided into 6
      subgroups with 10 rats each for sacrifice at 0, 4, 7, 14, 21, and 30 days after
      surgery. All surgical procedures were performed 3 months after alloxan diabetes
      induction. BS was measured in all intestinal anastomoses. Fragments of ileum and
      colon anastomoses were taken for hydroxyproline concentration (HP) and total
      tissue protein (TP) dosages. RESULTS: Anastomotic BS was significantly decreased
      (P<0.05) in ileum and colon of G4 and G5 diabetic groups up to 7 and 14 days
      after surgery, respectively, compared with G2 and G3 normal control groups.
      Anastomotic HP and TP content did not significantly differ between diabetic and
      normal control operated groups in ileum or colon at all evaluation times.
      CONCLUSION: Experimental diabetes leads to impaired intestinal anastomotic
      strength during early surgical wound repair, but does not appear to be implicated
      with collagen synthesis capacity.

PMID- 19169546
TI  - Systematic review of animal research.

PMID- 19169545
TI  - Biodistribution of samarium-153-EDTMP in rats treated with docetaxel.
AB  - PURPOSE: Many patients with metastatic bone disease have to use
      radiopharmaceuticals associated with chemotherapy to relieve bone pain. The aim
      of this study was to assess the influence of docetaxel on the biodistribution of
      samarium-153-EDTMP in bones and other organs of rats. METHODS: Wistar male rats
      were randomly allocated into 2 groups of 6 rats each. The DS (docetaxel/samarium)
      group received docetaxel (15 mg/kg) intraperitoneally in two cycles 11 days
      apart. The S (samarium/control) group rats were not treated with docetaxel. Nine
      days after chemotherapy, all the rats were injected with 0.1 ml of samarium-153
      EDTMP via orbital plexus (25 microCi). After 2 hours, the animals were killed and
      samples of the brain, thyroid, lung, heart, stomach, colon, liver, kidney and
      both femurs were removed. The percentage radioactivity of each sample (% ATI/g)
      was determined in an automatic gamma-counter (Wizard-1470, Perkin-Elmer,
      Finland). RESULTS: On the 9th day after the administration of the 2nd
      chemotherapy cycle, the rats had a significant weight loss (314.50+/-22.09g)
      compared (p<0.5) to pre-treatment weight (353.66+/- 22.8). The % ATI/g in the
      samples of rats treated with samarium-153-EDTMP had a significant reduction in
      the right femur, left femur, kidney, liver and lungs of animals treated with
      docetaxel, compared to the control rats. CONCLUSION: The combination of docetaxel
      and samarium-153-EDTMP was associated with a lower response rate in the
      biodistribution of the radiopharmaceutical to targeted tissues. Further
      investigation into the impact of docetaxel on biodistribution of samarium-153
      EDTMP would complement the findings of this study.

PMID- 19169547
TI  - Brazilian law for scientific use of animals.
AB  - The Brazilian scientific community claimed for a definitive systematization and
      for comprehensive and realistic national rules, to provide guidance and
      regulation, instead of sanctions, so that the question of scientific research
      involving animals could be better contemplated. This is beginning to occur now
      with Law no. 11.794, sanctioned by the President of the Republic on November 8,
      2008. PURPOSE: To describe the evolution of Brazilian regimentation for
      scientific use of animals and to analyze Law no. 11.794. METHODS: The legislation
      about the use of animals in teaching and in scientific research in Brazil and in
      Rio de Janeiro State was identified and discussed. RESULTS: Until now, there was
      no updated general and systematizing rule regarding animal vivisection and
      experimentation for didactic or scientific purposes. The only specific law dates
      back to 1979 and was not regimented. More recent laws equated the practice of
      scientific experiments to acts of abuse and mistreatment of animals, when
      alternative technology was available. Municipal laws that restricted the
      scientific practice of vivisection and experimentation with animals were created
      in the cities of Rio de Janeiro and Florianopolis. CONCLUSION: With the claim and
      collaboration of the scientific community, the sanction of Law no. 11.794
      regarding the scientific use of animals represented an invaluable advance in
      spite of the presence of some points that eventually may require another type of
      treatment. The new Law states that it will be regimented within 180 (one-hundred
      and-eighty) days, when some of these points could be better elucidated.

PMID- 19169548
TI  - Natural invertebrate hosts of iridoviruses (Iridoviridae).
AB  - Invertebrate iridescent viruses (IIVs) are icosahedral DNA viruses that infect
      invertebrates, mainly insects and terrestrial isopods, in damp and aquatic
      habitats. Exhaustive searches of databases resulted in the identification of 79
      articles reporting 108 invertebrate species naturally infected by confirmed or
      putative iridoviruses. Of these, 103 (95%) were arthropods and the remainder were
      molluscs, an annelid worm and a nematode. Nine species were from marine habitats.
      Of the 99 non-marine species, 49 were from terrestrial habitats and 50 were
      aquatic, especially the aquatic stages of Diptera (44 species). The abundance of
      records from species of Aedes,Ochlerotatus and Psorophora contrasts markedly with
      a paucity of records from species of Anopheles,Culex and Culiseta. Records from
      terrestrial isopods are numerous (19 species), although the diversity of IIVs
      that infect them is mostly unstudied. IIV infections have been reported from
      every continent, except Antarctica, but there are few records from Africa,
      southern Asia and Latin America. Most reports describe patent IIV infections as
      rare whereas inapparent (covert) infection may be common in certain species. The
      relationship between particle size and iridescent colour of the host is found to
      be consistent with optical theory in the great majority of cases. Only 24
      reported IIVs from insect hosts have partial characterization data and only two
      have been subjected to complete genome sequencing. I show that the rate of
      publication on IIVs has slowed from 1990 to the present, and I draw a number of
      conclusions and suggestions from the host list and make recommendations for
      future research efforts.

PMID- 19169549
TI  - Wolbachia in two populations of Melittobia digitata Dahms (Hymenoptera:
      Eulophidae).
AB  - We investigated two populations of Melittobia digitata Dahms, a gregarious
      parasitoid (primarily upon a wide range of solitary bees, wasps, and flies), in
      search of Wolbachia infection. The first population, from Xalapa, Mexico, was
      originally collected from and reared on Mexican fruit fly pupae, Anastrepha
      ludens Loew (Diptera: Tephritidae); the other, from Athens, Georgia, was
      collected from and reared on prepupae of mud dauber wasps, Trypoxylon politum Say
      (Hymenoptera: Crabronidae). PCR studies of the ITS2 region corroborated that both
      parasitoid populations were the same species; this potentially provides a useful
      molecular taxonomic profile since females of Melittobia species are superficially
      similar. Amplification of the Wolbachia surface protein gene (wsp) confirmed the
      presence of this endosymbiont in both populations. Sequencing revealed that the
      Wolbachia harbored in both populations exhibited a wsp belonging to a unique
      subgroup (denoted here as Dig) within the B-supergroup of known wsp genes. This
      new subgroup of wsp may either belong to a different strain of Wolbachia from
      those previously found to infect Melittobia or may be the result of a
      recombination event. In either case, known hosts of Wolbachia with a wsp of this
      subgroup are only distantly related taxonomically. Reasons are advanced as to why
      Melittobia - an easily reared and managed parasitoid - holds promise as an
      instructive model organism of Wolbachia infection amenable to the investigation
      of Wolbachia strains among its diverse hosts.

PMID- 19169550
TI  - First come, first serve: "sit and wait" behavior in dung beetles at the source of
      primate dung.
AB  - Dung beetles (Coleoptera: Scarabaeidae: Scarabaeinae) compete intensively for
      dung resources, and most species forage in the understory. Here, we describe the
      unique behavior of one dung beetle species, Canthon aff. quadriguttatus
      (Olivier), associated with two species of monkeys from Peru. We observed this
      beetle species on the genital and anal regions of the brown titi monkey,
      Callicebus brunneus (Wagner), and subsequently falling with dung as the monkeys
      defecated. The same association was also observed with the bald-faced saki
      monkey, Pithecia irrorata irrorata (Gray). Using the ' sit and wait' at the
      source behavior, C. quadriguttus may arrive first at the dung resource, possibly
      out-competing other dung beetle species. This paper is the first report of this
      behavior for C. aff. quadriguttatus on the brown titi monkey and bald-faced saki
      monkey from southeastern, Amazonian Peru. We discuss this behavior in the context
      of competition and resource partitioning, and also speculate as to why C. aff.
      quadriguttatus has been found on both monkey species.

PMID- 19169551
TI  - [Thermal requirements and estimate of the annual number of generations of
      Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) on strawberry
      crop].
AB  - Frankliniella occidentalis (Pergande) is one of the major strawberry pests in
      southern Brazil. The insect causes russeting and wither in flowers and fruits
      reducing commercial value. In this work, the thermal requirements of the eggs,
      larvae and pupae of F. occidentalis were estimated. Thrips development was
      studied in folioles of strawberry plants at six constant temperatures (16, 19,
      22, 25, 28 and 31 degrees C) in controlled conditions (70 +/- 10% R.H. and 12:12
      L:D). The number of annual generations of F. occidentalis was estimated for six
      strawberry production regions of Rio Grande do Sul State based on its thermal
      requirements. Developmental time of each F. occidentalis stages was proportional
      to the temperature increase. The best development rate was obtained when insects
      were reared at 25 masculineC and 28 masculineC. The lower threshold and the
      thermal requirements for the egg to adult stage were 9.9 masculineC and 211.9
      degree-days, respectively. Considering the thermal requirements of F.
      occidentalis, 10.7, 12.6, 13.1, 13.6, 16.5 and 17.9 generations/year were
      estimated, respectively, for Vacaria, Caxias do Sul, Farroupilha, Pelotas, Porto
      Alegre and Taquari producing regions located in Rio Grande do Sul State, Brazil.

PMID- 19169553
TI  - A longitudinal study of two species of Belostoma Latreille (Heteroptera:
      Belostomatidae): allometry and ontogeny.
AB  - The multivariate allometric growth patterns from longitudinal data of leg and
      rostral segments of all instars of Belostoma elegans (Mayr) and B. cummingsi De
      Carlo are presented for the first time, and the allometric coefficients are
      compared. The segments of the middle and hind legs present allometric
      coefficients with opposite polarity to those of forelegs. This discrepancy in the
      ontogenetic trajectories may be due to the different functions of the legs. The
      foreleg main function is to capture of the prey, while the middle and hind legs
      are adapted to swimming. The relative size of rostral segments is an important
      taxonomic character in Belostoma. In B. cummingsi, the proximal segment is longer
      than the middle one, while in B. elegans they are subequal. Our purpose is to
      explain these differences through the analysis of their ontogenetic trajectories
      in an attempt to illuminate the morphological differences among species from a
      developmental perspective.

PMID- 19169552
TI  - Phylogeographical analysis of neotropical Rhagoletis (Diptera: Tephritidae): did
      the Andes uplift contribute to current morphological differences?
AB  - Neotropical Rhagoletis species are arranged in four groups:
      nova,psalida,striatella and ferruginea, which include 18 species. On both sides
      of the Andes, the evolution of morphological differences among these groups has
      been suggested to be related to the Andes uplift process. In order to test this
      hypothesis, a phylogenetic analysis of morphological and molecular data was
      performed. The results suggest that: 1) Neotropical species of Rhagoletis
      constitute a separate group from Paleartic and North American species, with the
      only exception being a member of the striatella group having a certain
      association with the northern species. 2) Neotropical species seem to form a
      monophyletic clade, although statistical support for this is weak. 3) The split
      of South American Rhagoletis from other groups was dated at 4.333 million years
      ago, which is before the emergence of a continuous landbridge between Central and
      South America. 4) Within species distributed in South America, morphological and
      molecular data were coincident, placing species of the ferruginea group separate
      from the other Neotropical Rhagoletis. 5) The divergence of the ferruginea group
      from the other groups was dated at 3.882 million years ago, which is before the
      last uplift of the Andes. These results suggest that diversification of the
      ferruginea,psalida and nova groups, on each side of the Andes, was the result of
      a vicariant separation followed by dispersal and isolation processes. Thus, these
      results support the hypothesis that the Andes uplift has played an important role
      in Neotropical Rhagoletis diversification.

PMID- 19169554
TI  - Five new species of the neotropical genus Ganodes Townes (Hymenoptera:
      Ichneumonidae).
AB  - Five new species of the Neotropical genus Ganodes Townes, from Mexico, Venezuela,
      Brazil and Argentina, are described and illustrated: G. bocaina, G. garciai, G.
      mexicanus, G. townesi and. G. wahli. A key to seven species is provided,
      including two species described previously, G. balteatus Townes and G. matai
      Gauld.

PMID- 19169555
TI  - [Bionomics data and descriptions of the immatures of Calyptocephala gerstaeckeri
      Boheman (Coleoptera: Chrysomelidae), pest of the oil palm (Elaeis guineensis J.)
      and camedor palm (Chamaedorea elegans Mart.) (Arecaceae) in Tabasco, Mexico].
AB  - Characters of the external morphology of egg, larval instars and pupae of
      Calyptocephala gerstaeckeri Boheman, insect pest of oil palm (Elaeis guineensis
      J.) and camedor palm (Chamaedorea elegans Mart.) in the State of Tabasco, Mexico,
      are described and illustrated. Some bionomics data are also presented. The specie
      was reared in the laboratory on young oil palm plants.

PMID- 19169556
TI  - A new species of Anagrus (Hymenoptera: Mymaridae) from Amazonas, Brazil.
AB  - A new fairyfly species from the Neotropics, Anagrus (Anagrus) amazonensis
      Triapitsyn, Querino & Feitosa, sp. n., is described and illustrated. Anagrus
      Haliday is a large genus of Mymaridae (Hymenoptera), which now includes eight
      species recorded from Brazil. This new species attacks eggs of damselflies
      (Odonata: Zygoptera).

PMID- 19169557
TI  - New records of Brazilian cicadas including the description of a new species
      (Hemiptera: Cicadoidea, Cicadidae).
AB  - A new species of Proarna Stal is described from southern Brazil. Proarna gianucai
      sp. nov. is distinguished by its coloration and genitalia. The species inhabits
      coastal dune environments and is associated with the perennial grass Panicum
      racemosum (P. Beauv.) Spreng. Adults are active from December to March. The first
      records of Carineta durantoni Boulard, Carineta gemella Boulard, Carineta
      pilifera Walker, Fidicina christinae Boulard & Martinelli, Fidicina torresi
      Boulard & Martinellli, Fidicinoides determinata (Walker), Fidicinoides distanti
      (Goding), Fidicinoides glauca (Goding), Majeorona truncata Goding, and Zammara
      columbia Distant for Brazil are provided. The new species and new records bring
      the total cicada diversity of Brazil to 146 species.

PMID- 19169558
TI  - Morphological caste studies in the neotropical swarm-founding Polistinae wasp
      Angiopolybia pallens (Lepeletier) (Hymenoptera: Vespidae).
AB  - Neotropical swarm-founding wasps present polygynic colonies and a great variation
      in relation to caste differentiation, ranging from species in which queens and
      workers are similar in shape and size to those where variation in shape and size
      is conspicuous. Canonical discriminant analysis and Bonferroni t-test analysis on
      morphometric data collected from eight body parts of specimens from nine colonies
      of Angiopolybia pallens (Lepeletier) were undertaken as a step towards to a
      better understanding on caste differenciation in Epiponini. All specimens were
      dissected to verify the ovary developmental stage, and the spermatheca was
      removed to check for the mating status. Females were then grouped as queens
      (mated with developed ovaries), intermediates (virgin with developed ovaries) and
      workers (virgin with undeveloped ovaries). Even though differences were found for
      some measurements in seven out of the nine colonies evaluated, multivariate
      analysis (Wilks' lambda values) indicated castes could not be reliably
      distinguished only by morphology. We conclude that morphological differences
      among A. pallens castes are low or absent, reflecting a possible groundplan for
      the Epiponini, i.e. a post-imaginal pattern of caste differentiation.

PMID- 19169560
TI  - [Bioactivity of Trichilia pallida Swartz (Meliaceae) derived molecules on Tuta
      absoluta (Meyrick) (Lepidoptera: Gelechiidae)].
AB  - Dichloromethane (DIC) leaf and fruit extracts of Trichiliapallida Swartz were
      obtained for the isolation and identification of molecules with insecticidal
      activity against the tomato leafminer, Tuta absoluta (Meyrick). DIC leaf extracts
      of T. pallida yielded six compounds, the triterpenes 24-methylenecycloarta-3beta
      ol (TRIT-1), 24-methylenecycloarta-3beta-26-diol (TRIT-2) and cycloarta-23-eno
      3beta,25-diol (TRIT-3), the sterols 24-methylene-3,22-dihydroxycholesterol (EST
      1), 24-methylenecholesterol (EST-2) and 24-methylene-3beta,4beta,22
      trihydroxycholesterol (EST-3), while the fruit extract yielded the limonoid
      gedunine (LIM). These molecules were dissolved in acetone and sprayed at 0.1% on
      tomato leaflets infested with newly-hatched larvae. Larval mortality at day 5 and
      9 after infestation, larval and pupal developmental time and survival, pupal
      weight and adult malformation were evaluated. TRIT-1, EST-1 and LIM were the most
      effective against T. absoluta due to larval development arrestment and reduced
      larval survivorship.

PMID- 19169559
TI  - Use of by-products rich in carbon and nitrogen as a nutrient source to produce
      Bacillus thuringiensis (Berliner)-based biopesticide.
AB  - The amount and sources of carbon and nitrogen used to produce Bacillus
      thuringiensis (Berliner)-based biopesticide may influence the quality of the
      final product. The objective of this research was to test different levels of
      carbon and nitrogen: medium 1 - 1.5% maize glucose + 0.5% soy flour, medium 2 -
      3.0% maize glucose + 1.0% soy flour, medium 3 - 1.0% maize glucose + 3.0% soy
      flour and medium 4 - Luria Bertani (LB) + salts (FeSO4, ZnSO4, MnSO4, MgSO4). The
      seed culture was produced in LB medium plus salt, under agitation (200 rpm) for
      18h at 30 masculineC. The strain 344 of Bt was used (B. thuringiensis var
      tolworthi - belonging to the Embrapa's Bt Bank). The pH was measured at regular
      intervals. and After culturing for 96h, the pH of the four tested media was
      basified (6.91 and 8.15), the number of spores yielded 4.39 x 10(9) spores/ml in
      medium 3, where the amount of protein is high. The dry biomass weight accumulated
      in media 3 was 39.3 g/l. Mortality of 2-day-old larvae Spodoptera frugiperda
      (J.E. Smith) was 100% when using Bt produced in media 3 and 4. CL50 for medium 3
      was 8.4 x 10(6) spores/ml. All tested media were satisfactory to Bt growth, and
      medium 3 wass the most promising to be used on a large scale Bt-based
      biopesticide production.

PMID- 19169561
TI  - [Factors affecting Diatomaceous earth effectiveness in the control of Alphitobius
      diaperinus (Panzer) (Coleoptera: Tenebrionidae) adults].
AB  - Diatomaceous earth (DE) is a potential alternative to control the lesser mealworm
      of poultry farms Alphitobius diaperinus (Panzer). Our study aimed to understand
      the role of some of the environmental and insect behavioral factors play on DE
      effectiveness, such as the substrate (chicken food and poultry house litter),
      temperature and DE repellent activity on lesser mealworm adults. Mortality was
      higher at the highest temperature (32 masculineC), and it increased with DE
      concentration (53 and 84% respectively, for concentrations of 86 and 172 g/m(2))
      (P < 0.05). The substrate also influenced DE effectiveness: 95% mortality was
      observed in the feed, against 4% in the poultry litter. Part of these results can
      be attributed to the removal of DE particles by the poultry bedding, as supported
      by scanning electron microscopy (SEM) observations and rhodamine concentration on
      the surface of the insects. As to insect behavior, DE had a repellent effect,
      since trap capture decreased nearly 50% in traps containing DE as opposed to
      those containing only food. Therefore, environmental factors do affect the DE
      effectiveness, and they must be taken into consideration when looking into
      developing control strategies in the field.

PMID- 19169562
TI  - [Diagrammatic scale of Aceria guerreronis Keifer (Acari: Eriophyidae) damage in
      coconut].
AB  - Aceria guerreronis Keifer is an important pest of coconut worldwide. Due to the
      lack of standardized methods to quantify damage of this eryophyid, a diagrammatic
      scale with indices of 1, 2, 4, 8, 16, 32, 48 and 70% of damage caused by A.
      guerreronis was elaborated and tested to accuracy, precision and reproduction of
      the estimations. To validate the scale, fruits with different levels of damage
      were previously measured with the program Assess(R) and submitted to 10
      inexperienced evaluators with or without the scale (1 feminine evaluation) and
      seven days after (2 feminine evaluation) with the same evaluators, using
      digitized pictures of the same fruits in a different sequence. The accuracy and
      precision of each evaluator was determined through linear regression between
      observed and estimated damage. Without using the scale, evaluators were less
      precise as seven out of 10 overestimated the damage, while evaluators provided
      with the scale were much more accurate. Also, evaluations with the aid of the
      scale were much more reproducible than without the scale. The scale was used to
      determine the relationship between infestation and damage levels caused by A.
      guerrerronis. The relationship between infestation and damage fitted by the
      equation lny = 4.948 - 0.121x + 1.789 lnx (R(2) = 99.87%, P < 0.0001). Therefore,
      these findings show that it is possible to estimate A. guerreronis population
      density on infested coconut fruits by using the diagrammatic scale.

PMID- 19169563
TI  - Effect of diet composition on the development of the floodwater Mosquito
      Ochlerotatus (Ochletotatus) albifasciatus (Macquart) (Diptera: Culicidae).
AB  - One important step for the colonization of Ochlerotatus albifasciatus (Macquart)
      is to determine the optimal conditions for larval rearing, which makes possible
      the development of experiments comprising larval rearing in the laboratory. In
      this research the effect of diet composition on the development of
      O.albifasciatus was studied. For this purpose, cohorts of 20 first instars were
      reared using five diets: 1:1 mix of yeast and TetraMin(R), 1:1 mix of fine and
      coarse organic matter, grass cuts soaked in water for 1h or 24h before larvae
      incorporation, and 1:1:1 mix of grass cuts, fine organic matter and coarse
      organic matter. Survival was recorded for each cohort, while development time
      from first instar to pupa, and adult wing length were recorded for each
      individual. The effects of the diet on the observed traits were analyzed by one
      way ANOVA. Both survival and wing length were affected by diet, being
      significantly higher (79-100% and ~ 4.46 mm) on diets consisting of organic
      matter or organic matter plus grass than on those consisting of yeast plus
      TetraMin(R) or grass. Development time was not affected by the diet, although the
      shortest time (8.1 to 8.3 days) and lower variation between replicates were
      recorded when larvae were reared using organic matter or organic matter plus
      grass. Thus, it is concluded that the diets consisting of organic matter or a mix
      of it and grass are the most effective for O.albifasciatus rearing.

PMID- 19169564
TI  - New records of fruit flies (Diptera: Tephritidae), wild hosts and parasitoids
      (Hymenoptera: Braconidae) in the Brazilian Amazon.
AB  - Anastrepha anomala Stone was obtained from Parahancornia amapa (Huber) Ducke
      (Apocynaceae) fruits, and Anastrepha hastata Stone from Cheiloclinium cognatum
      (Miers.) (Hippocrateaceae) in the State of Amapa, Brazil. Two braconids,
      Doryctobracon sp. and Opius bellus Gahan, were reared from the latter fruit fly
      species. This is the first record of P. amapa as a fruit fly host. C. cognatum is
      the first host known to A. hastata. Both braconids are also the first records of
      parasitoids for this species.

PMID- 19169565
TI  - [Trichoptera imatures in Parana river basin, Goias state, with new records for
      genera].
AB  - Distribution of Trichoptera along Parana River Basin, Goias State, with new
      records for genera, is presented. Eighteen sample sites were made along the basin
      during the rain (March and December/2003) and dry (July/2003 and August/2004)
      seasons. Surber and D net were used for sampling all habitats.

PMID- 19169566
TI  - First report of Raoiella indica Hirst (Acari: Tenuipalpidae) in South America.
AB  - The presence of the red palm mite, Raoiella indica Hirst is recorded for the
      first time in South America. High populations and severe damages caused by this
      new invasive mite were found on coconut and banana leaves in Sucre (10 degrees
      27' 47' N and 64 degrees 10' 38' W) and Monagas (9 masculine46'60' N and 63
      masculine12'0' W) states in northeastern Venezuela.

PMID- 19169567
TI  - Herbivory on bracken (Pteridium spp.) by Bolax palliata Burmeister (Coleoptera:
      Scarabaeidae), a poliphagous beetle of the Venezuelan Andes.
AB  - Herbivore attack by Bolax palliata Burmeister is reported on two sympatric
      bracken species: Pteridium caudatum (L.) Maxon and P. arachnoideum (Kaulf.).
      Laboratory and field observations revealed a preference for the last of the two
      species. Available phytochemical information suggests it could be based on
      differences in concentration of condensed tannins.

PMID- 19169568
TI  - First report and differential colonization of Passiflora species by the B biotype
      of Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) in Brazil.
AB  - This note is the first report of Bemisia tabaci (Gennadius) biotype B colonizing
      passionvine in Brazil. We examined the colonization of nine Passiflora species by
      a wild B type population under greenhouse conditions. P. amethystina Mikan was
      the most preferred species for oviposition and colonization, whereas P. suberosa
      L., P. coriacea Juss. and two commercially cultivated species, P. alata Curtis
      and P. edulis Sims f. flavicarpa Degener, were mostly uncolonised. P. morifolia
      Mast., P. cincinnata Mast., P. foetida L. and P. caerulea L. showed intermediate
      levels of colonization. Such differential colonization might suggest some degree
      of resistance by certain Passiflora species or oviposition preference by B.
      tabaci.

PMID- 19169569
TI  - [ELSA Brasil: the greatest epidemiological study in Latin America].

PMID- 19169570
TI  - Imported and autochthonous cases in the dynamics of dengue epidemics in Brazil.
AB  - OBJECTIVE: To estimate the basic reproduction number (R0) of dengue fever
      including both imported and autochthonous cases. METHODS: The study was conducted
      based on epidemiological data of the 2003 dengue epidemic in Brasilia, Brazil.
      The basic reproduction number is estimated from the epidemic curve, fitting
      linearly the increase of initial cases. Aiming at simulating an epidemic with
      both autochthonous and imported cases, a 'susceptible-infectious-resistant'
      compartmental model was designed, in which the imported cases were considered as
      an external forcing. The ratio between R0 of imported versus autochthonous cases
      was used as an estimator of real R0. RESULTS: The comparison of both reproduction
      numbers (only autochthonous versus all cases) showed that considering all cases
      as autochthonous yielded a R0 above one, although the real R0 was below one. The
      same results were seen when the method was applied on simulated epidemics with
      fixed R0. This method was also compared to some previous proposed methods by
      other authors and showed that the latter underestimated R0 values. CONCLUSIONS:
      It was shown that the inclusion of both imported and autochthonous cases is
      crucial for the modeling of the epidemic dynamics, and thus provides critical
      information for decision makers in charge of prevention and control of this
      disease.

PMID- 19169571
TI  - Presumed unconstrained dispersal of Aedes aegypti in the city of Rio de Janeiro,
      Brazil.
AB  - OBJECTIVE: To evaluate dispersal of Aedes aegypti females in an area with no
      container manipulation and no geographic barriers to constrain mosquito flight.
      METHODS: A mark-release-recapture experiment was conducted in December 2006, in
      the dengue endemic urban district of Olaria in Rio de Janeiro, Southeastern
      Brazil, where there is no evident obstacle to the dispersal of Ae. aegypti
      females. Mosquito traps were installed in 192 houses (96 Adultraps and 96
      MosquiTRAPs). RESULTS: A total of 725 dust-marked gravid females were released
      and recapture rate was 6.3%. Ae. aegypti females traveled a mean distance of
      288.12 m and their maximum displacement was 690 m; 50% and 90% of females flew up
      to 350 m and 500.2 m, respectively. CONCLUSIONS: Dispersal of Ae. aegypti females
      in Olaria was higher than in areas with physical and geographical barriers. There
      was no evidence of a preferred direction during mosquito flight, which was
      considered random or uniform from the release point.

PMID- 19169572
TI  - Tooth loss and associated factors in adolescents: a Brazilian population-based
      oral health survey.
AB  - OBJECTIVE: To estimate tooth loss among adolescents and its factors associated.
      METHODS: Data from 16,833 participants of the Brazilian Oral Health Survey 2002
      2003 were analyzed. The outcome studied was tooth loss of at least one tooth.
      Independent variables included geographical localization, gender, skin color, per
      capita income, education gap, dental service utilization and fluoridated water
      supply at the local level. Crude and adjusted prevalence ratios were estimated
      using Poisson regression for each Brazilian macroregion and nationwide. RESULTS:
      The prevalence of at least one tooth loss was 38.9% (95% CI 38.2%;39.7%).
      Adolescents living in localities with non-fluoridated water supply were 40% more
      likely to have tooth loss compared with those living in areas with fluoridated
      water supply. There was seen a strong association (p<0.01) between non
      fluoridated water supply and tooth loss prevalence in the Northeast. In other
      Brazilian regions this association was confounded for distal variables, mainly
      socioeconomic variables, reinforcing regional inequalities. CONCLUSIONS: High
      prevalence of tooth loss among Brazilian adolescents shows a need for targeted
      dental actions including prevention at earlier ages, treatment of affected teeth
      and universal access to fluoridated water.

PMID- 19169573
TI  - Effect of air pollution on lung function in schoolchildren in Rio de Janeiro,
      Brazil.
AB  - OBJECTIVE: To assess the association between daily exposure to air pollution and
      lung function in school children. METHODS: Panel study with a random sample of
      118 students (between 6 and 15 years of age), enrolled in a public school of the
      city of Rio de Janeiro, state of Rio de Janeiro, and living within 2 km of the
      study site. Data on students' characteristics were obtained with a questionnaire,
      including the International Study of Asthma and Allergies in Childhood - ISAAC.
      Daily peak expiratory flow measurements were taken to measure lung function.
      Daily data on PM10, SO2, O3, NO2 and CO levels, temperature and humidity were
      provided by a portable monitor. Repeated measurements of lung function were
      associated with pollutant levels with a multilevel model adjusted for time trend,
      temperature, air humidity, exposure to smoking at home, presence of asthma,
      height, sex, weight and age of children. RESULTS: Mean peak expiratory flow was
      243.5 l/m (sd=58.9). The lowest mean peak expiratory flow was 124 l/m, and the
      highest, 450 l/m. For the 10 microg/m(3) increase in PM10, there was a 0.34 l/min
      decrease in mean peak flow on the third day. For the 10 microg/m(3) increase in
      NO2, there was a decrease between 0.23 l/min and 0.28 l/min in mean peak flow
      after exposure. CO and SO2 effects on students' peak flow were not statistically
      significant. O3 showed a protective result: an increase in 10 microg/m(3) of O3
      would be associated, after a day of exposure, with a 0.2 l/min increase in mean
      lung function. CONCLUSIONS: Even within acceptable levels most of the time, air
      pollution, especially PM10 and NO2, was associated with a decrease in lung
      function in children living in the city of Rio de Janeiro.

PMID- 19169574
TI  - Causes for the decline in child under-nutrition in Brazil, 1996-2007.
AB  - OBJECTIVE: To describe the evolution of prevalence of under-nutrition among
      Brazilian underfives between 1996 and 2007, and to identify major factors
      responsible for this evolution. METHODS: Data analyzed are from two Demographic
      Health Surveys carried out in Brazil in 1996 and 2006/7 based on probabilistic
      samples of roughly 4 thousand children under five years of age. Identification of
      factors responsible for temporal variation in prevalence of under-nutrition
      (height-for-age below -2 Z-scores; WHO 2006 standard) took into account changes
      in the distribution of four potential determinants of nutritional status.
      Statistical modeling of the independent association between these determinants
      and risk of under-nutrition, and calculation of 'partial attributable fractions'
      were used to determine the relative importance of each factor in the evolution of
      infant under-nutrition. RESULTS: Prevalence of under-nutrition fell by
      approximately 50%, from 13.5% (95%CI: 12.1%; 14.8%) in 1996 to 6.8% (5.4%; 8.3%)
      in 2006/7. Two-thirds of this reduction could be attributed to favorable
      evolution in the four factors studied: 25.7% to increased maternal schooling;
      21.7% to increased purchasing power of families; 11.6% to expansion of
      healthcare; and 4.3%to improvements in sanitation. CONCLUSIONS: The 6.3% annual
      rate of decline in the proportion of children with height-for-age deficits
      indicates that, in another ten years, child malnutrition in Brazil may no longer
      be a public health issue. Achieving this will depend on the maintenance of
      economic and social policies that have favored an increase in purchasing power
      among the poor, and on public investments aimed at completing the
      universalization of access to essential services such as education, health, and
      sanitation among the Brazilian population.

PMID- 19169575
TI  - Sensitivity and specificity of criteria for classifying body mass index in
      adolescents.
AB  - OBJECTIVE: To estimate the prevalence of overweight among adolescents using
      different body mass index (BMI) classification criteria, and to determine
      sensitivity and specificity values for these criteria. METHODS: Weight, height,
      and tricipital and subscapular skinfolds in 934 adolescents (462 males and 472
      females) aged 14-18 years (mean age 16.2; SD=1.0) of the city of Florianopolis,
      Southern Brazil, in 2001. Percent fat estimated based on skinfold measurements (>
      or =25% in males and > or =30% in females) was used as a gold-standard for
      determining specificity and sensitivity of BMI classification criteria among
      adolescents. RESULTS: The different cutoff points used for classifying BMI in
      general resulted in similar prevalence of overweight (p>0.05). Sensitivity of the
      evaluated criteria was high for males (85.4% to 91.7%) and low for females (33.8
      to 52.8%). Specificity of all criteria was high for both sexes (83.6% to 98.8%).
      CONCLUSIONS: Estimates of prevalence of obesity among adolescents using different
      BMI classification criteria were similar and highly specific for both sexes, but
      sensitivity for females was low.

PMID- 19169576
TI  - Breastfeeding, complementary feeding, overweight and obesity in pre-school
      children.
AB  - OBJECTIVE: To analyze the association of overweight and obesity with
      breastfeeding and complementary feeding in pre-school children. METHODS: Cross
      sectional study with 566 children, enrolled in private schools of the city of Sao
      Paulo, Southeastern Brazil, in 2004-2005. The dependent variable was overweight
      and obesity. Body Mass Index percentile curves were employed to classify
      children's nutritional status, considering values > or =P85 and <P95 as
      overweight, and values > or =P95 as obesity. The following explanatory variables
      were analyzed: child and family socio-demographic characteristics; birth weight;
      parents' nutritional status; breastfeeding; complementary feeding; and current
      feeding. Analysis of association between explanatory variables and outcome was
      performed with simple logistic regression and multiple logistic regression with
      hierarchical model. RESULTS: Prevalence of overweight and obesity in the
      population studied was 34.4%. The following were protective factors against
      overweight and obesity: exclusive breastfeeding for six months or more (95% CI
      [0.38;0.86]; OR=0.57; p=0.02) and breastfeeding for more than 24 months (95% CI
      [0.05;0.37]; OR=0.13; p=0.00). CONCLUSIONS: Results suggest that breastfeeding
      can protect children against overweight and obesity, thus representing yet
      another advantage of maternal milk.

PMID- 19169577
TI  - Breast milk donation: women's donor experience.
AB  - OBJECTIVE: To describe the characteristics of donation behavior and identify
      reasons, beliefs and feelings relative to this practice, based on the reports of
      donor women. Personal and social-environmental aspects, which seem to affect
      donation behavior in donors and former donors, were also investigated. METHODS:
      An exploratory, descriptive and cross-sectional study was carried out with women
      donors at two breast-milk banks within the public health system of the Brazilian
      Federal District. Data was collected from July to September 2005. The
      participants were 36 women, aged 14 to 33 years (average=24.78; SD=5.22), with
      different levels of schooling, 58.3% of which were first-time mothers. Data
      gathering was based on interviews carried out during home visits. In addition to
      descriptive statistical analyses of quantitative data, a qualitative data
      categorical analysis was also performed. RESULTS: The most frequently reported
      reasons for donating breast milk were altruism and excess milk production. The
      most frequent time interval for donation was 13 days after delivery. Contact by
      phone with the milk bank was the most common means of communication used by the
      majority of participants (n=22) to obtain information that enabled the donating
      process. CONCLUSIONS: Psychosocial aspects identified and the experience of
      donors can contribute to the empowerment of the formal and informal social
      donation-support network, in addition to serving as a driver for the
      implementation of technical and policy strategies in promoting future donation
      practices.

PMID- 19169578
TI  - [Parent's perspective on child rearing and corporal punishment].
AB  - OBJECTIVE: To describe parents' current perception of corporal punishment
      associated to child rearing and its practices. METHODOLOGICAL PROCEDURES: There
      were studied 31 family members whose children were warded due to child abuse
      complaints (12) and not warded (19) at a health care unit and a local social
      service unit in the city of Belo Horizonte (Southeastern Brazil) in 2006. Data
      was collected through semi-structured interviews and speech analysis was
      performed grouped by subjects and categories. ANALYSIS OF DISCOURSE: There was
      limitation of the respondents' speeches based on their production means. There
      was a diversity of conceptions on child rearing and its practices and corporal
      punishment was reported by all parents, even among those who expressed strong
      disapproval of this practice. Speeches were characterized by heterogeneity and
      polyphony with emphasis on the tradition speech, the religious speech and the
      popular scientific speech. Respondents did not express concepts of legal
      interdiction of corporal punishment or its excesses. CONCLUSIONS: The culture of
      corporal punishment of children is changing; tradition approving it has weakened
      and prohibition has been slowly adopted. Reinforcing legal actions against this
      practice can contribute to speed up the process to end corporal punishment of
      children.

PMID- 19169579
TI  - Paternity: social responsibility of man's role as provider.
AB  - OBJECTIVE: To analyze meanings attributed to paternity by men who are fathers.
      STUDY DESIGN: Study with a qualitative approach and gender-theory focus,
      performed in the city of Joao Pessoa, Northeastern Brazil, in 2003. A total of
      ten men, whose children had been cared for in the pediatric outpatient clinic of
      a university hospital, participated in the study. Information analyzed was
      obtained with semi-structured interviews. Critical discourse analysis technique
      was employed to analyze participants' speech. DISCOURSE ANALYSIS: Participants in
      the study viewed paternity as a new social role, more closely associated with
      material support for the family than the dimension of affective involvement with
      the child. However, participants experienced a transition process where the
      traditional father lived with those whose affective dimension of paternity was
      found to be the main concern of being a father. CONCLUSIONS: The meaning and
      concrete exercise of paternity were found in an area of responsibilities that
      predominantly reproduces the traditional father, but also recreates the father's
      role, including the affective dimension.

PMID- 19169580
TI  - Family Health Program professionals' view on family structures and health
      implications.
AB  - OBJECTIVE: To describe perception of family structures and understanding of a
      healthy family by Programa Saude da Familia (Family Health Program) team members.
      METHODS: Research with a qualitative approach, employing the focus group
      technique, and involving the Program professionals from the city of Campo Bom,
      Southern Brazil, between June and August 2005. Sample was comprised of 12
      professionals, including doctors, nurses, nursing technicians and community
      health agents. The following issues were investigated: the meaning of family; the
      meaning of the role of family; type of family most frequently cared for by
      professionals; the meaning of a healthy family; and types of family causing more
      difficulties of care. The methodological instrument used was content analysis.
      RESULTS: Two main categories were observed: family structures, where a great
      diversity of arrangements was found; and healthy family, where the predominance
      of speech is consistent with a multifaceted view on health, involving political,
      social, economic and cultural aspects. Professionals identify and respect
      distinct family structures and adapt medical treatment accordingly. CONCLUSIONS:
      Findings reveal that professionals are willing to deal with the different family
      structures present in their routine.

PMID- 19169581
TI  - Women's perspective in the evaluation of the Program for the Humanization of
      Antenatal Care and Childbirth.
AB  - OBJECTIVE: To analyze the importance of inclusion, from women's perspective, in
      the evaluation of the Program for the Humanization of Antenatal Care and
      Childbirth, carried out by the Brazilian Ministry of Health. METHODOLOGICAL
      PROCEDURES: This qualitative study was based on primary data collected in 2003 in
      an evaluation of the Program conducted in seven towns spread out among Brazil's
      five geographic regions. These sites were selected from a Federal Government data
      base utilized for quantitative analysis. Women attended by the Program were
      considered key informants when primary data was collected. Sixteen focal groups
      were performed in the primary care units. The Collective Subject Speech (CSS)
      method was used for qualitative analysis. The theoretical concepts of
      accessibility and Paideia Health within the framework of public health were used
      to interpret the findings. ANALYSIS OF RESULTS: The Program standardizes
      procedures to be taken in antenatal care and childbirth for all health services
      in the country, including the flow among these services. However, analysis of
      women's discourse in the focal groups elucidated the existence of dissonances
      between their needs and desires and many of the program's recommendations.
      Pregnant women thus choose among available services and professionals and try to
      set up their own schedules which, in turn, do not correspond to those set up by
      the program. This discrepancy damages the bond women establish with the health
      services and creates obstacles for the control of the activities actually
      provided by the health services to the women. CONCLUSIONS: Analysis of the
      Program based on women's perspective identified aspects that might result in more
      humanized and effective antenatal care, if they are taken into account in the
      redefinition or correction of the Program schedule Miolo abstract Miolo abstract
      Miolo abstract.

PMID- 19169582
TI  - Strategic Demarche in a mother and child hospital unit.
AB  - OBJECTIVE: The strategic demarche approach questions the dissociation between the
      strategic direction and the operational level of an institution, in search of a
      continuous and flexible planning of projects. The objective of the study is to
      describe the application of this approach in the evaluation of a hospital unit.
      METHODOLOGICAL PROCEDURES: The approach was adapted to and applied at a mother
      and child unit of a public state hospital in the municipality of Serra,
      Northeastern Brazil. Hospital management analysis was conducted with the indirect
      involvement of institutional agents, who acted as key informants from April to
      July, 2006. Besides the meetings with key informants, data was also collected
      from the following sources for the year 2005: Inpatient records from the
      obstetric center, maternity and nursery wards, statistical report of the
      perinatal outcomes from the mother and child unit; records from the ambulatory
      care unit for breastfeeding. RESULTS: The most valued segments were: The Neonatal
      Intensive Care Unit, The Obstetric Surgery Center, and The Obstetric Center. The
      Program of Humanized Care for the Mother and Newborn was also highly valued. The
      main weaknesses pointed out were the low level of articulation with the network
      (partnership with municipal network); the lack of hospital beds and technological
      investment necessary for responding adequately to the demand; excessive
      professional rotation due to temporary assignments and the deficient
      implementation of the humanization policies, compromising the strategic success
      factors of the segments. CONCLUSIONS: The results indicate the method's potential
      for discussing the hospital mission and performing analysis of hospital
      management, pointing out strategies for improving the quality and competitiveness
      of the segments and for greater integration and insertion in the service network.

PMID- 19169583
TI  - [Differences in living conditions and health between cities: construction of a
      composite indicator].
AB  - OBJECTIVE: To describe an index to identify inequities in living conditions and
      health and its relationship with health planning. METHODS: Variables and
      indicators that would reflect demographic, economic, environment and education
      processes as well as supply and production of health services were applied for
      nondimensional scaling and clustering of 5,507 Brazilian municipalities. Data
      sources were the 2000 Census and the Brazilian Ministry of Health information
      systems. Z-score test statistic and cluster analysis were performed allowing to
      defining 4 groups of municipalities by living conditions. RESULTS: There was seen
      a polarization between the group with the best living conditions and health
      (Group 1) and the group with the worst living conditions (Group 4). Group 1
      consisted of municipalities with larger populations while Group 4 comprised
      mainly the smallest municipalities. As for Brazilian macroregions, municipalities
      in Group 1 are clustered in the south and southeast and those in Group 4 are in
      the Northeast. CONCLUSIONS: The living conditions and health index comprises
      reality dimensions such as housing, environment and health which allows to
      identifying the most vulnerable municipalities and can provide input for setting
      priorities, and developing criteria for more equitable financing and resource
      allocation.

PMID- 19169584
TI  - Ecological analysis of accidents and lethal violence in Vitoria, Southeastern
      Brazil.
AB  - OBJECTIVE: To analyze the socioeconomic background and its relationship with
      spatial distribution of mortality due to violence. METHODS: Ecological study
      conducted to explore the space distribution of mortality due to violence in the
      city of Vitoria, Southeastern Brazil, between 2000 and 2003, based on population
      and socioeconomic information. Mortality data were correlated with information on
      victim's place of residence, type of violence, gender, and skin color. Data were
      analyzed using space average, odds ratio, and cluster analysis. RESULTS: There
      were reported 828 deaths due to violence during the study period, accounting for
      17% of all deaths in the city. Of these, 72% were homicides, 21.8% traffic
      accidents, and 6% suicides. Violence victims were mostly young black males,
      living in poorer areas of the city. In contrast, as for suicide and traffic
      accidents, the victims were older white females living in the wealthiest area of
      the city. CONCLUSIONS: The study showed that violence is a phenomenon occurring
      in all socioeconomic levels but black people at the lowest level are more likely
      to die from homicides while white well-off people are more likely to die from
      suicide and traffic accidents.

PMID- 19169585
TI  - [HIV/HCV coinfection at an university hospital in Recife, Brazil].
AB  - OBJECTIVE: To estimate the prevalence of hepatitis C virus (HCV) infection and
      risks factors associated with coinfection in HIV-positive individuals. METHODS: A
      cross-sectional descriptive study was conducted with 343 HIV patients attended at
      a university hospital in Recife, Northeastern Brazil, from March to December
      2003. A standardized questionnaire about risk factors was administered. Serum
      samples were analyzed for anti-HCV antibodies using enzyme-linked immunosorbent
      assay (ELISA), HCV-RNA using reverse transcription-polymerase chain reaction (RT
      PCR), and genotyping using the ABI 377 (PE Biosystems). Univariate and
      multivariate analyses and multiple logistic regression were performed. RESULTS:
      HCV prevalence was 4.1% (14/343) using ELISA and 3.2% (11/343) using RT-PCR. The
      most common genotypes were 1b (45%), 3 (33%) and 1a (22%). Co-infection was
      higher among those aged 30 to 39 years, and predominantly in males (64.3 %). In
      the multiple logistic regression, the variable blood transfusion was the single
      remaining risk factor for HCV (OR=4.28; 95% CI 1.44;12.73). CONCLUSIONS: The
      prevalence of HIV/HCV coinfection was low. Blood transfusion was a risk factor
      and HCV genotype 1b was the most frequently found.

PMID- 19169586
TI  - Use of analgesics in adults with pain complaints: prevalence and associated
      factors, Turkey.
AB  - OBJECTIVE: Use of analgesics has been increasingly recognized as a major public
      health issue with important consequences in Turkey. The objective of the study
      was to determine the prevalence and patterns of analgesics usage and associated
      factors in adults with pain complaints. METHODS: A cross-sectional study was
      conducted in 15 cities selected from five demographic regions in Turkey. The
      study sample population comprised 1.909 adults 18-65 age groups suffering from
      pain. The sampling method was multi-step stratified weighted quota-adjusted
      sampling. Data were collected by face-to-face interviews using a semi-structured
      survey questionnaire consisting of 28 questions. Odds ratios were produced by
      logistic regression analyses. RESULTS: The prevalence of analgesic use was 73.1%,
      and it was higher in females (75.7%; p<0.05), in subjects 45-54 years (81.4%;
      p<0.05), in subjects in rural areas (74.6%; p<0.05), in subjects in northern
      region (84.3%; p<0.05), in illiterate subjects (79.1%; p>0.05), and in subjects
      of lower socioeconomic status (74.1%; p>0.05). One in ten of the participants
      used non-prescription analgesics. Non-prescription analgesics were more prevalent
      among the 55-65 age groups (18.1%; p<0.05), among female (11.6%; p>0.05), among
      the urban population (10.7%; p>0.05), and in subjects of lower middle
      socioeconomic status (13.2%; p<0.05). Logistic regression showed statistically
      significant ORs only for age groups, duration of education, socioeconomic status,
      and demographic regions (p<0.05). CONCLUSIONS: The results showed that the
      prevalence of analgesic use and prescription analgesic use is high in Turkey, and
      their use is related to sociodemographic characteristics.

PMID- 19169587
TI  - Validity of the Brazilian version of WHOQOL-BREF in depressed patients using
      Rasch modelling.
AB  - OBJECTIVE: To assess the validity of the Brazilian version of the World Health
      Organization Quality of Life Instrument - Abbreviated version (WHOQOL-BREF) in
      adults with major depression, using Rasch modelling. METHODS: Study analyzing
      data from the baseline sample of the Longitudinal Investigation of Depression
      Outcomes in Brazil, including a total of 208 patients with major depression
      recruited in a primary care service in Porto Alegre (Southern Brazil), in 1999.
      The Center for Epidemiological Studies Depression Scale was used to assess
      intensity of depression; the WHOQOL-BREF to assess generic quality of life; and
      the Composite International Diagnostic Interview version 2.1 for the diagnosis of
      depression. RESULTS: In the Rasch analysis, the four domains of WHOQOL-BREF
      showed appropriate fit to this model. Some items needed adjustments: four items
      were rescored (pain, finances, services, and transport); two items (work and
      activity) were identified as having dependency of responses, and one item was
      deleted (sleep) due to multidimensionality. CONCLUSIONS: The validation of the
      WHOQOL-BREF Brazilian version using Rasch analysis complements previous
      validation studies, evidencing the robustness of this instrument as a generic
      cross-cultural quality of life measure.

PMID- 19169588
TI  - Quality of life in trauma victims six months after hospital discharge.
AB  - OBJECTIVE: Trauma is the third most important cause of death in Brazil. However,
      its impact on survivors' quality of life has been scarcely studied in this
      country. This study aimed to assess trauma victims' quality of life, cared for in
      an emergency hospital unit, six months after discharge. METHODS: A total of 35
      patients from the emergency unit of a university hospital in the city of Ribeirao
      Preto, Southeastern Brazil, were included in this study, between 2005 and 2006.
      Patients were interviewed in their homes, six months after hospital discharge.
      The short version of the World Health Organization Quality of Life (WHOQOL-BREF)
      instrument was applied to assess the physical, psychological, social
      relationships, and environmental domains. Associations between domain scores and
      hospital stay, age, sex and Injury Severity Score variables were analyzed with
      linear regression models. RESULTS: Significant reduction in quality of life was
      found in the group studied, when compared to samples of normal people in national
      and international studies, especially as regards the physical, psychological, and
      environmental domains. The social relationships domain revealed the highest mean
      scores, with 69.7 points, whereas the environmental domain received the lowest
      score (52.4 points), both on the percentage scale. Variables associated with the
      physical domain were hospital stay (p=0.02), age (p<0.01) and sex (p=0.03). The
      analysis did not show association with the variables studied for the remaining
      domains. CONCLUSIONS: Trauma victims showed a reduction in quality of life
      scores. Even though the physical aspect was the most affected, there is evidence
      that the psychological and environmental domains remained far from the ideal
      conditions expected for the general population.

PMID- 19169589
TI  - Feasibility of general hospitals psychiatric units in Brazil.
AB  - OBJECTIVE: To comprehend the stigma against people with mental disorders still
      persists in the culture of general hospitals and acts as a limiting factor in the
      implementation of psychiatric units in general hospitals in Brazil.
      METHODOLOGICAL PROCEDURES: A qualitative social survey was outlined based on
      action research strategy as of the agreement to adopt a psychiatric unit in a
      general hospital in Taubate, Southeastern Brazil. Data was obtained through
      interviews, participant observation and talks on the psychiatric unit project
      given to the hospital's clinical staff. RESULTS: The investment made by the
      healthcare authority enabled the stigmatizing conceptions (violence, moral
      weakness and untreatability) present in the hospital culture in question to be
      resignified by means of clinical and sanitary discussions, which enabled the
      implementation of the psychiatric unit. The analysis showed that these concepts
      persist in this context because of a healthcare system that limits the access of
      people with mental disorders. CONCLUSIONS: The attitude of the healthcare
      authority, who decided to adequately fund the general hospital's psychiatric unit
      and exerted his influence over the hospital, was decisive for the outcome of the
      case. The main difficulty in implementing psychiatric units at general hospitals
      is not the overcoming the existing stigma in the culture of general hospitals,
      but rather a difficulty which is strategic in nature: the lack of an affirmative
      policy for these units.

PMID- 19169590
TI  - Sociology, medicine and the construction of health-related sociology.
AB  - Starting from a paper about closing the gap between sociology and medicine in
      Brazil and the United Kingdom that was published in 1971, a historical update was
      made with the aim of reflecting on the new shapes of health-related teaching and
      research within the social and human sciences, in these two countries. The
      methodology was qualitative and the study was developed using secondary data. The
      reflections were developed through the authors' immersion in Brazilian and
      British realities. It was concluded that the interface between sociology and
      health has expanded, although persistent old difficulties exist in relation to
      the structure and focus of the healthcare system, medical school power and
      medical student culture.

PMID- 19169591
TI  - Tuberculosis and intestinal parasitism among indigenous people in the Brazilian
      Amazon region.
AB  - The objective of the survey was to estimate the frequencies of tuberculosis and
      intestinal parasitosis in indigenous communities at the locality of Iauarete,
      Northern Brazil, in 2001. This was a cross-sectional survey (n=333) aimed at
      obtaining demographic data and biological samples for sputum and feces
      examinations. Among the 43 individuals with respiratory symptoms, six presented
      alcohol/acid-fast bacilli in sputum. Intestinal parasitosis was significantly
      more frequent among the Hupda population than among the Indians living in other
      districts (37.5% vs. 19.3% for Ascaris lumbricoides, 32.4% vs. 16.3% for
      Trichuris trichiura, 75% vs. 19.3% for hookworms, 75% vs. 35.4% for Entamoeba
      histolyticaD dispar and 33.3% vs. 10.7% for Giardia lamblia). It is concluded
      that tuberculosis and intestinal parasitism are frequent in these communities,
      thus requiring control measures and better medical care.

PMID- 19169592
TI  - Estimate of DMFT index using teeth most affected by dental caries in twelve-year
      old children.
AB  - The objective of the study was to develop regression models to describe the
      epidemiological profile of dental caries in 12-year-old children in an area of
      low prevalence of caries. Two distinct random probabilistic samples of
      schoolchildren (n=1,763) attending public and private schools in Piracicaba,
      Southeastern Brazil, were studied. Regression models were estimated as a function
      of the most affected teeth using data collected in 2005 and were validated using
      a 2001 database. The mean (SD) DMFT index was 1.7 (2.08) in 2001 and the
      regression equations estimated a DMFT index of 1.67 (1.98), which corresponds to
      98.2% of the DMFT index in 2001. The study provided detailed data on the caries
      profile in 12-year-old children by using an updated analytical approach.
      Regression models can be an accurate and feasible method that can provide
      valuable information for the planning and evaluation of oral health services.

PMID- 19169593
TI  - [Ordinal logistic regression in epidemiological studies].
AB  - Ordinal logistic regression models have been developed for analysis of
      epidemiological studies. However, the adequacy of such models for adjustment has
      so far received little attention. In this article, we reviewed the most important
      ordinal regression models and common approaches used to verify goodness-of-fit,
      using R or Stata programs. We performed formal and graphical analyses to compare
      ordinal models using data sets on health conditions from the National Health and
      Nutrition Examination Survey (NHANES II).

PMID- 19169594
TI  - [Co-infection HIV/Leishmania: a serious problem of Public Health].

PMID- 19169595
TI  - [Use of psychoactive substances and risky behavior].

PMID- 19169596
TI  - [Human cutaneous myiasis: a case report].
AB  - Myiasis is a self-limiting infestion of tissues by fly larvae commonly referred
      as maggots. A case of cutaneous myiasis in a 61 year old woman admitted to the
      Department of Emergency of S. Giovanni Hospital in Rome (Italy) is reported in
      the present note. The patient, a religious sister, returned to Rome from a
      mission trip of few weeks in Edea (Cameroon, Africa), was suffering from a
      subclavicular furuncular skin lesion; one maggot was surgically removed and
      submitted for parasitological examination. Based on the maggot shape and size,
      the travel history and the clinical presentation, a maggot of Cordylobia spp. has
      been identified (Calliphoridae, Diptera). This case calls for an awareness of its
      possibility as a cause of furuncular skin lesion, particularly in subjects
      returning from an endemic country for Cordylobia spp. (Africa).

PMID- 19169597
TI  - Exploiting the ambulatory blood pressure monitoring via chronobiometric and
      chaosbiometric methods for a more exhaustive diagnostic approach to arterial
      hypertension.
AB  - Presently, the ambulatory (A) blood (B) pressure (P) monitoring (M) is mainly
      used for diagnosing arterial hypertension (AH) in some special clinical
      conditions in which the causal sphygmomanometry appears not to be enough
      exhaustive. However, it must be pointed out that the actual approach to ABPM is
      almost simplistic, only consisting in a biometric analysis of discrete raw
      temporal values for systolic (S) and diastolic (D) BP and heart rate (HR). It
      must be stressed that BP and HR are hemodynamic variables characterized by a well
      established circadian rhythm (C) in their 24-h physiological values. Therefore,
      an appropriate chronobiometric approach, via Single Cosinor method, can improve
      the diagnostic value, its optimal oscillatory curve reducing all the biometric
      information to three parameters, i.e., MESOR (M, mean level of oscillation),
      Amplitude (A, extent of oscillation from M) and Acrophase (phi, timing of A with
      respect to local midnight). Accordingly, one can detect whether the BP CR is
      still manifest, as it is in essential hypertension (EH), or altered , as it is in
      secondary hypertension (SH). Therefore, by using the discriminant analysis for
      the three multivariate parameters, M, A, phi, of the BP cosine curve, one can
      statistically predict whether a new monitored hypertensive patient has a
      significant probability to be affected by EH or SH. Interestingly, by applying a
      further chronobiometric integration analysis, i.e., the Cosint analysis, it is
      possible to estimate the area under the BP oscillatory curve, for calculating the
      overall, diurnal, nocturnal, hourly pressure load (Baric Impact, BI) in terms
      respectively of mm2 Hg/24-h, mm2 Hg/16-h, mm2Hg/8-h, mm2 Hg/1-h. By comparing the
      overall BI of the new monitored hypertensive patient to its upper reference
      limit, one can estimate how much is the Baric Excess (Hyperbaric Impact, HI)
      caused by the personal hypertensive regimen. Finally, by using the chaos method
      of fractal interpolation to BP 24-h values, it is possible to establish whether
      or not the monitored hypertensive subject is presumably at risk of unpredictable
      high BP values (presumable risk of hypertensive crisis).

PMID- 19169598
TI  - [Alexithymic features and emotional distress in patients with chronic tension
      type headache (CTTH) and medication-overuse headache (MOH)].
AB  - AIMS: The study examined the role of alexythimia and emotional distress in
      patients with diagnosis of chronic headaches (tension-type and medication overuse
      headache). MATERIALS AND METHODS: The Toronto Alexithymia Scale (TAS-20)and the
      Rapid Stress Assessment (RSA) were administered to a sample of 104 patients (day
      hospital and outpatients) composed by 70 with CTTH and 34 with MOH. RESULTS: In
      total sample, 16.3% of patients were classified as alexithymics, 20.2% as
      intermediates and 63.5% as non-alexithymics, according to the TAS-20 criteria.
      Anxiety and Lack of social support (RSA) showed the higher values, yet the RSA
      mean profile didn't exceed the normative range. Alexithymics scored higher on all
      the RSA scales; significant positive correlations were also obtained among RSA
      and TAS-20 values. MOH patients were more frequently classifi ed as alexithymics
      and reported higher values on Aggressiveness scale (RSA) compared to CCTH
      patients. CONCLUSIONS: Findings supported a link between alexithymia and
      emotional distress, as an index of psychological maladjustment in chronic
      headache patients.

PMID- 19169599
TI  - [Evaluation of total energy expenditure in adult, overweight and free-living
      subjects. A comparison between two methods: Factorial Method vs SenseWear Armband
      "Metabolic Holter"].
AB  - OBJECTIVE: Evaluation of SenseWear Armband functional and structural
      characteristics and comparison between TEE value from Factorial Method and
      Metabolic Holter. MATERIAL AND METHODS: The study has involved a homogeneous
      group of 21 adult, overweight (25BMI30 Kg/m(2)) and free-living subjects, 9 men
      and 12 women, with an average age of 34.9 +/- 14.5 (20-60 years old). TEE
      valuation has been performed for each subject by means of Factorial Method and,
      secondly, through the application of SenseWear Armband (Bodymedia Inc.,
      Pittsburgh, PA, USA). RESULTS: Values recorded by Armband overestimate Factorial
      values of 14%. The Student's t Test has reported significant results (t = 3.540;
      p = 0.002). Spearman's Correlation has showed the following values of r = 0.696
      and p = 0.001. CONCLUSIONS: The analysed methods can't be superimposed because
      the study has showed a signifi cant difference between the reported values. In
      spite of all that, Spearman study has highlighted a remarkable statistic relation
      between the techniques. In conclusion, SWA and FM seem to allow a corresponding
      diagnosis.

PMID- 19169600
TI  - Creatinine clearance and blood pressure: a 34-year circadian study.
AB  - BACKGROUND AND OBJECTIVE: The first circadian study of the 361st Medical
      Laboratory, USAR, was conducted in May 1969 during the Annual Military Training
      at Brook Army Hospital, Fort Sam Houston, Texas. The study was approved by the
      Surgeon General, 5th US Army, and was designed to establish a circadian database
      for 63 medically relevant variables of 13 young members of the Unit. The
      subsequent studies, all in the month of May, in 1979, 1988, 1993,1998, and 2003,
      followed the same protocol and were conducted at Edward Hines Jr., Veterans
      Administration Hospital, after approval by Human Studies Subcommittees. Since a
      reduction in Creatinine Clearance (CrCl) to the level of 60 ml/min/1.73m2 signals
      the onset of kidney malfunction and since a concurrent increase in blood pressure
      (BP) >140/90 mm Hg, contributes greatly to an unfavorable cardiovascular
      prognosis, it seemed prudent to examine possible changes in these and in other
      relevant variables in a group of young Army men, which may have developed over a
      34 year period of time. MATERIAL AND METHODS: Thirteen US Army male volunteers
      (23-27y of age) served as subjects in the 1969 study. A majority of these men,
      two additional Army men and two non-military subjects, participated in subsequent
      studies: 1979 (7,2,1), 1988 (8,2,1), 1993 (5,4,1), 1998 (7,2,2), 2003 (7,2,1). In
      each study, subjects were admitted to a hospital ward, were given medical
      examination including a 12-lead electrocardiogram and followed the same Protocol.
      Lights "OUT" at 22:30h and "ON" at 06:30h. The meals, hospital 2400-calorie
      diets, were served at 17:30, 07:30 and at 13:30h. Vital signs were measured
      immediately after each 3h urine collections, around the clock, and bloods were
      collected every 3h. Blood, plasma, serum, saliva and urines were analyzed for
      numerous analytes including creatinine, using automated laboratory systems.
      Kidney functions were assessed using the measured and estimated glomerular
      filtration rates. RESULTS: Over the 34y study span, 16 men provided sixty-one 24h
      profiles for CrCl-related variables (urine volume, creatinine, and serum
      creatinine) and fifty-eight profiles for BP. Using all normalized data, a
      significant circadian rhythm was found for each of these variables. Significant
      circadian variations in SBP, DBP, serum and urine creatinine, and urine volume,
      were evident with peak levels, on average, occurring in the evening hours.
      CONCLUSIONS: In healthy subjects, age was associated with an increase in SBP and
      urine volume and with a decrease in urine creatinine. In diabetic subjects, aging
      was associated with increases in both blood pressure and Creatinine Clearance. It
      is interesting to note that for the 3 subjects who at a later date developed
      diabetes, the CrCl levels were higher than the 5 age-matched controls during each
      study year, over the entire 34y observation span, including the period prior to
      diagnosis. Clin Ter 2008; 159(6):409-417.

PMID- 19169601
TI  - A finding of myocardial uptake at a bone scintigraphy with Tc-99m HDP.
AB  - We present a patient admitted to our Department for a Tc-99m HDP three-phase bone
      scintigraphy to evaluate a hip prosthesis. Delayed images showed diffuse
      myocardial uptake at whole body scan. In such cases, several diseases should be
      considered in the differential diagnosis.

PMID- 19169602
TI  - Psoriasis disappearance after the first phase of an oncologic treatment: a
      serendipity case report.
AB  - Psoriasis is a multifaceted disorder with psychosocial and physical aspects that
      negatively impact the quality of life. Strategies of treatment must address both
      rapid control of the disease and maintenance of benefits. For short and long-term
      control of localized psoriasis, recent data support the combined use of topical
      corticosteroids and either calcipotriene or tazarotene which seem to be the most
      effective approach. For generalized disease, UVB treatment provides the safest
      means of achieving long-term control of the disease. Acitretin is a very helpful
      adjunct for improving the efficacy of phototherapy. For patients with severe,
      refractory disease, methotrexate may be most effective while cyclosporine may be
      most valuable for patients needing rapid, short-term improvement. Other
      molecules, with different pharmacological properties, are actually under
      consideration. Herein it is reported a case of a 55 year old male, who refers, 2
      weeks after the fi rst cycle of oncologic therapy with gemcitabine and cisplatin
      for a lung neoplasm, about the complete remission of the psoriasis on both
      fingernails and scalp, suffered since almost ten years. Three months after the
      fortuitous detection of the psoriasis disappearance, there is no further evidence
      of psoriatic lesions.

PMID- 19169603
TI  - [Inherited macular pattern dystrophies: a case report, diagnostic methodology,
      state of the art].
AB  - Discreet chorioretinal spots are a characteristic of the Pattern Dystrophies (PD)
      that include a small group of disorders with pigmentary changes in the posterior
      fundus, including the macular region. These disorders are transmitted as either
      Autosomal Recessive or Dominant trait and can be observed in association with
      maternal diabetes mellitus and deafness. This report was performed with three
      aims: 1. to present a clinical case of PD in a young girl and her family; 2. to
      elucidate the complex panel of diagnostic Hi-Tech techniques; 3. to describe the
      State of the Art in this field of retinal alterations. The complex diagnostic
      procedure, when examined at the light of the consolidated bibliography, confirms
      the importance of the new Hi-Tech instrumentation as an indispensable tool for an
      early diagnosis of PD.

PMID- 19169604
TI  - [Splenic infarction after warfarin discontinuation during atrial fibrillation].
AB  - We describe a case of patient with splenic infarction, admitted to our department
      for sudden abdominal pain and fever after discontinuation of anticoagulant
      therapy for atrial fibrillation, complicating a dilated myocardiopathy and
      mechanical prosthetic valve. Diagnosis of splenic infarction was made by enhanced
      contrast computed tomography, while ultrasounds and radiography were negative.
      Anticoagulant therapy, gold-standard treatment, was followed by fast clinical
      improvement. Moreover, splenic infarction should be considered in all cases of
      acute or chronic pain in left hypochondrium and especially in patients with
      emboligenous cardiopathies or atrial fibrillation, the most common arrhythmia
      source of peripheral embolism in clinical practice.

PMID- 19169605
TI  - Alzheimer disease: primary ischemia concept and promising therapy.
AB  - The important role of cerebral blood flow (CBF) in Alzheimer disease (AD) has
      been increasingly recognized in recent years. An abundance of data (The Rotterdam
      Study, see text) has shown the decline of CBF velocity with transcranial Doppler,
      confirming earlier data obtained with the xenon133 method. In spite of these
      data, AD is still considered a neurodegenerative disorder with secondary CBF
      changes. This work is a critical evaluation of earlier literature because of
      cogent reasons for the adoption of a new concept of AD as a primary ischemic
      disorder. Reports of lacking correlation between severity of CBF defi cit and
      degree of tissue damage or clinical fi ndings serve as evidence for primary
      ischemia because of the incompatibility with the concept of secondary
      ischemia.The CBF defi cit is thought to be due to the human upright gait in here
      dopredisposed individuals. As to therapy and prevention, a very simple, cheap and
      promising treatment is suggested (head-down-therapy).

PMID- 19169606
TI  - [Optimal role of docetaxel in adjuvant chemotherapy for early stage HER2-negative
      breast cancer].
AB  - The fundamental imperative of adjuvant treatment of early breast cancer is to
      improve long-term survival and minimize toxicity. The inclusion of docetaxel in
      adjuvant chemotherapy regimens has improved patient survival in comparison to
      anthracycline-containing regimens, even if the incidence of acute side effects
      has increased in some studies. However, late or persistent toxic effects are
      becoming more important due to an increasing proportion of patients remaining
      disease free after treatment for early breast cancer. Several studies have
      recently reported that docetaxel-containing regimens without anthracyclines are
      equally active, and have no apparent cardiotoxicity. At present, docetaxel-based
      combinations represent an appropriate choice in the adjuvant treatment of HER2
      negative breast cancer, and several studies are ongoing aiming at a better
      evaluation of the efficacy of this agent in order to optimize its role.

PMID- 19169607
TI  - Docetaxel in the adjuvant therapy of HER-2 positive breast cancer patients.
AB  - Considering the clinical benefit of trastuzumab in advanced breast cancer, fi ve
      prospective adjuvant randomized trials have recently been completed and early
      results have been published. Two of them, (NSABP-B31 and NCCTG N9831), employed
      anthracycline-containing regimens with sequential paclitaxel, with or without
      trastuzumab. The third study, HERA trial, randomized patients after adjuvant
      chemotherapy into an observational arm, one or two years of trastuzumab. Results
      of these studies, after a median follow up of 2-3 years confirm a DFS and OS
      benefit for the experimental arms. The worst rate of cardiotoxicity, in terms of
      incidence of CHF, with the use of trastuzumab and anthracycline based regimens
      was 4.1% in the trastuzumab arm of the NSABP-B31 trial. Among the fi ve
      trastuzumab trials, two, BCIRG 006 and FinHer, employed docetaxel-based regimens.
      The innovative BCIRG 006 trial compared ACdocetaxel (T) with two trastuzumab
      containing regimens, ACTH, and a non-anthracycline-containing regimens, TCH, with
      a clear advantage in DFS for both trastuzumab arms. Data from the second interim
      analysis indicate that, in the subgroup of patients without co-amplification of
      topoisomerase 2 (TOPO-2), the arm without trastuzumab (ACT) showed a DFS
      significantly poorer that in the other arms; moreover, if we consider the lower
      toxicity of TCH regimen in comparison with anthracycline-containing arms, the
      innovative statements offered by BCIRG 006 trial appear evident, and these
      findings opened an important question about the consolidated employment of
      anthracyclines in adjuvant setting.The FinHer trial was a small trial testing a
      short course of trastuzumab (9 weeks) concomitantly with a chemotherapy including
      docetaxel, and there was a significant advantage in DFS for the trastuzumab based
      arms, without relevant toxicity and without any cardiotoxicity. Although data
      from all trastuzumab adjuvant trials, and without particulary from BCIRG-006 and
      FinHer trials, appear very intriguing, further follow-up is required.

PMID- 19169608
TI  - Optimal sequence of anthracyclines and taxanes as adjuvant breast cancer
      treatment.
AB  - Results from randomized trials evaluating taxane versus non-taxane containing
      regimens in adjuvant breast cancer treatment indicate an advantage in DFS and OS
      for the taxane-arms, but the best schedule of administration, in combination with
      anthracyclines or in sequence, is still a debated issue, even if the sequential
      strategy appears to be less toxic. Up to now, the majority of clinical trials
      employed the "standard" sequence, with anthracycline-based combinations fi rst,
      followed by taxanes. Few small phase II trials evaluated the reverse sequence,
      with taxanes administered fi rst, most of them in metastatic or neoadjuvant
      setting, suggesting efficacy and lower toxicity. An important issue to be
      considered is the hypothesized differences in the ability of the drugs to induce
      cross-resistance to each other, as suggested by data of a preclinical study, and
      from clinical study with a cross-over design; results of these trials suggest
      that the best strategy would be to administer a taxane prior to an anthracycline,
      also according to the Norton and Simon hypothesis. Moreover, trials evaluating
      the best sequence of anthracyclines and taxanes in adjuvant breast cancer setting
      are of small sample size, and an adequately powered randomized phase III trial is
      needed before definitive conclusions are reached.

PMID- 19169609
TI  - Helicobacter pylori infection and gastric MALTomas: an up-to-date and therapy
      highlight.
AB  - During the last 20 years Helicobacter pylori (Hp) has been, undoubtly, the star
      of gastroenterology and microbiology, so much to deserve the "Nobel prize 2005"
      for biology and medicine to its discoverers. More recently, an increased interest
      arised on Hp and its linkages with other medical fi elds such as immunology,
      surgery and dentistry. The outcome of the pathologies due to such bacterium is
      dependent on many factors, including bacterial genotype, host physiology and
      genetics, and environmental factors such as diet. In spite of its clear
      involvement in some pathologies like acute and chronic gastritis, peptic ulcer
      and gastric cancer, very little is known about another pathology recently proved
      to be closely associated to the infection by Hp: the gastric MALToma, which
      account for 7% of all newly diagnosed non-Hodgkin's lymphoma. The chronic
      infection of the gastric mucosa from Helicobacter pylori primes a complex
      pathogenic process which could determine the onset of the gastric cancer through
      some intermediary steps. On these bases, in 1994, the International Agency for
      Cancer Research (IARC) defined this bacterium a "class I carcinogenic agent" for
      gastric cancer. The MALT lymphomas are the most frequent lymphoid neoplasms of
      the digestive tract; we can also observe other and more rare lymphomatous tumours
      with specific clinical patterns, like the T-lymphoma associated with lymphomatous
      polyposis and enteropathy. The development of gastric lymphomas is usually
      preceded by the acquisition of lymphatic tissue, after inflammatory stimuli and
      particularly after the infection from Hp, which organizes itself with the
      characteristics of the MALT. Recently, a number of papers have highlighted the
      remarkable efficacy of Hp eradicating therapy in patients with low-grade MALT
      lymphoma of the stomach without other modalities, e.g. surgery and systemic
      chemotherapy. The aim of this study is to be helpful for a comprehensive
      understanding the possible connections between Hp and gastric MALT lymphoma,
      evaluating the best therapy strategies, surgical and non surgical, actually
      available for its treatment.

PMID- 19169610
TI  - Antioxidant properties of anesthetics: the biochemist, the surgeon and the
      anesthetist.
AB  - General anesthesia can impair immunological defense mechanisms while inducing an
      inflammatory reaction. Generalized inflammatory reactions involve leucocytes
      which in turn release inflammatory mediators and free oxygen radicals. General
      anesthetics include a series of gaseous and intravenous sedative-hypnotic agents
      indicated for induction and maintenance of general anesthesia as well as for
      sedation of intubated, mechanically ventilated adults in intensive care units
      (ICU). Some anesthetics, such as propofol, are characterized by a phenolic
      structure similar to that of alpha-tocopherol, and exhibit antioxidant properties
      that have been demonstrated both in vitro and in vivo. Similarly, other
      anesthetics show antioxidant and protective roles but this mechanism is to be
      related to their ability to induce antioxidant enzyme (i.e., heme oxygenase-1).
      The aim of the present review is to evaluate the antioxidant properties of
      anesthetics in various experimental models and if they may be considered
      efficient therapeutic tools in counteracting oxidative stress during general
      anesthesia and sedation in ICU.

PMID- 19169611
TI  - Suicide and mental illness in parents and risk of suicide in offspring: a birth
      cohort study.
AB  - BACKGROUND: A family history of completed suicide and psychiatric illness has
      been identified as risk factors for suicide. AIMS: To examine the risk of
      offspring suicide in relation to parental history of suicide and other parental
      risk factors. METHOD: The study population consisted of 7,177 adult offspring
      born 1959-1961 and their parents from the Copenhagen Perinatal Cohort. Cohort
      members and their parents who had committed suicide were identified in the Danish
      Causes of Death Registry (follow-up until December 31, 2005), while information
      on psychiatric hospitalisation history was obtained from the Danish Psychiatric
      Central Research Register. RESULTS: Forty-eight cohort members, 77 mothers and
      133 fathers had committed suicide during the follow-up. Independent of parental
      psychiatric illness and social status, parental suicide significantly increased
      suicide risk in offspring (hazard ratio 4.40 with 95% CI 1.81-10.69). A stronger
      effect of parental suicide was observed in offspring without a history of
      psychiatric hospitalisation. CONCLUSION: Parental history of suicide is a risk
      factor for suicide in offspring, but primarily in offspring without psychiatric
      hospitalisation.

PMID- 19169612
TI  - Effects of two insecticides on survival, growth and emergence of Chironomus
      riparius Meigen.
AB  - Effects of chlorpyrifos and cypermethrin on the survival, growth and emergence of
      Chironomus riparius were determined on a life-cycle study. Although neither
      cypermethrin nor chlorpyrifos affected larval survival or growth, a decrease in
      the number of emerged midges and in the number of females over males, as well as
      in female biomass, were found for both insecticides. The results from this study
      indicate that multiple biological endpoints and extended periods of exposure are
      needed in order to achieve a better screening of insecticide toxicity.

PMID- 19169613
TI  - Transformation of copper fractions in rhizosphere soil of two dominant plants in
      a deserted land of copper tailings.
AB  - This paper studied the transformation of copper fractions in rhizosphere and non
      rhizosphere soils of Festuca arundinacea and Trifolium repens in deserted land of
      copper tailings. The results showed that the proportion of organic-bound or
      exchangeable contents to the total contents of copper in rhizosphere increased by
      9.81 and 10.42%, while the contents of carbonate-bound or Fe-Mn oxides-bound
      decreased by 2.96 and 1.82%, respectively. The growth and absorption of F.
      arundinacea and T. repens accelerated the transformation of copper fractions in
      rhizosphere soils. The effect of root system of T. repens was prominently greater
      than that of F. arundinacea.

PMID- 19169614
TI  - Viewing the bilayer hydrocarbon core using neutron diffraction.
AB  - Membrane proteins fold, assemble and function within their native fluid lipid
      environment. Structural studies of fluid lipid bilayers are thus critically
      important for understanding processes in membranes. Here, we propose a simple
      approach to visualize the hydrocarbon core using neutron diffraction and
      deuterated lipids that are commercially available. This method should have broad
      utility in structural studies of the bilayer response to protein insertion and
      folding in membranes.

PMID- 19169615
TI  - CD38 in bovine lung: A multicatalytic NADase.
AB  - We report the kinetics and molecular properties of CD38 purified from bovine lung
      microsomal membranes after its solubilization with Triton X-100. The enzyme was
      found to be a novel member of a multicatalytic NAD(+)-glycohydrolase (NADase, EC
      3.2.2.6). It was able to utilize NAD( + ) in different ways, producing
      nicotinamide (Nam) and either adenosine diphosphoribose (ADPR, NADase activity)
      or cyclic ADPR (cADPR, cyclase activity); it also catalyzed the hydrolysis of
      cADPR to ADPR (cADPR, hydrolase activity). In addition, the enzyme catalyzed the
      pyridine base exchange reaction with conversion of NAD( + ) into NAD analogues.
      These data are evidence that CD38 is involved in the regulation of both NAD(+)
      and calcium-mobilizing agents, the concentration resulting in an essential enzyme
      that plays a key role in cellular energy and signal-transduction systems.

PMID- 19169616
TI  - Falciform ligament in pancreatoduodenectomy for protection of skeletonized and
      divided vessels.
AB  - BACKGROUND/PURPOSE: Pancreatic fistula, which is one of the main causes of late
      postpancreatectomy hemorrhage (PPH), is a common complication of
      pancreatoduodenectomy (PD). It may erode the anastomosis site and vascular wall
      in its vicinity, resulting in pseudoaneurysm formation and/or the rupture of
      major vessels. To protect the vessels near the area for pancreaticojejunostomy
      from potential pancreatic fistula, we have adopted a surgical option by which
      such vessels are separated from the pancreaticojejunostomy using a pedicled
      falciform ligament. We reviewed 36 patients who underwent PD that included this
      option. METHODS: After the PD was completed (before reconstructions), the
      pedicled falciform ligament was spread widely on the major vessels exposed during
      resection, and was fixed to the surrounding retroperitoneal connective tissue.
      These procedures enabled the complete separation of these vessels from the
      pancreaticojejunostomy. RESULTS: The mobilization and placement of the falciform
      ligament in the space between the pancreaticojejunostomy and the major vessels
      were successfully carried out without any complications. Although ten (28%)
      patients developed pancreatic fistula and three (8%) developed intraabdominal
      infection, none of the patients developed late PPH. CONCLUSIONS: The present
      surgical option is technically simple and easy, and may be an effective
      prophylactic measure against late PPH following PD.

PMID- 19169617
TI  - Usefulness of computed tomography during cholangiography for the diagnosis of
      multiple hepatic peribiliary cysts: a report of three cases with chronic liver
      disease.
AB  - Hepatic peribiliary cysts are composed of multiple tiny cysts along the larger
      portal tracts and have been reported to be harmless. On clinical images,
      peribiliary cysts resemble other diseases such as biliary dilatations,
      cholangitis, or periportal edema. Therefore, it is important to distinguish
      peribiliary cysts from these diseases using a combination of several imaging
      modalities. Herein, we report three cases of peribiliary cysts. The first case
      underwent laparotomy for the presumptive diagnosis of intrahepatic
      cholangiocarcinoma. In the remaining two cases, hepatic peribiliary cysts were
      diagnosed and laparotomy was avoided. Magnetic resonance cholangiography
      contributed to the diagnosis, owing to their characteristic distribution. In
      addition, computed tomography during cholangiography (cholangio-CT) demonstrated
      that the cysts had no communication with the intrahepatic biliary system.
      Therefore, cholangio-CT is considered to be the most useful modality for the
      diagnosis of peribiliary cysts.

PMID- 19169619
TI  - Spatial-temporal parameters of gait in women with fibromyalgia.
AB  - The aim of the present study was to determine if there are differences in such
      parameters among patients affected by fibromyalgia (FM) and healthy subjects and
      whether the degree of affectation by FM can decrease the gait parameters. We
      studied 55 women with FM and 44 controls. Gait analysis was performed using an
      instrumented walkway for measurement of the kinematic parameters of gait
      (GAITRite system), and patients completed a Spanish version of Fibromyalgia
      Impact Questionnaire (FIQ). Significant differences (p < 0.001) between FM and
      control groups were found in velocity, stride length, cadence, single support
      ratio, double support ratio, stance phase ratio, and swing phase ratio. There
      were significant inverse correlations between FIQ and velocity, stride length,
      swing phase, and single support, whereas significant direct correlations were
      found with stance phase and double support. Gait parameters of women affected by
      FM were severely impaired when compared to those of healthy women. Different
      factors such as lack of physical activity, bradikinesia, overweight, fatigue, and
      pain together with a lower isometric force in the legs can be responsible for the
      alterations in gait and poorer life quality of women with FM.

PMID- 19169620
TI  - Glucose blood levels after intra-articular steroid injection in diabetic and non
      diabetic patients.

PMID- 19169621
TI  - Increased frequencies of hysterectomy and early menopause in fibromyalgia
      patients: a comparative study.
AB  - The objective was to determine the relationship between symptoms of fibromyalgia
      (FM) and early menopause and hysterectomy. We included 115 postmenopausal
      patients with FM (mean age 54.6 +/- 7.6) and 67 rheumatoid arthritis (RA)
      patients (mean age 55.5 +/- 9) into our study. All patients were questioned about
      the severity of their symptoms of FM, anxiety, and depression by using a visual
      analog scale and FM impact questionnaire. Patients' history of menopause and
      hysterectomy were recorded. Menopause (<or=45 years) was accepted to be early.
      The frequencies of early menopause (38.3% vs. 13.4%, p = 0.001) and hysterectomy
      (16.5% vs. 6%, p = 0.039) in FM patients were significantly higher than in RA
      patients. While chronic widespread pain and other FM-related symptoms started
      after menopause in 58.3% of FM patients, the disease started after menopause in
      64.2% of RA patients (p > 0.05). FM-related symptoms started in 30 patients
      (26.1%) with FM with menopause or within the first postmenopausal year. When the
      clinical features of FM patients whose symptoms started within the first
      menopausal year were compared to other FM patients; it was observed that the
      frequency of early menopause was higher in the former group (p = 0.048). Duke
      anxiety and depression score was higher in patients with hysterectomy whose FM
      symptoms started within the first year of post-hysterectomy than other FM
      patients (9.1 +/- 2.7 vs. 6.7 +/- 2.7, p = 0.022). Early menopause and
      hysterectomy may be one of the factors contributing to the development of FM.

PMID- 19169622
TI  - Long-term experience with continuous duodenal levodopa-carbidopa infusion
      (Duodopa): report of six patients.

PMID- 19169623
TI  - Headache and soccer: a survey in professional soccer players of the Italian
      "Serie A".
AB  - The aim of the study was to assess the occurrence and the clinical features of
      primary headaches in a sample of players of the Italian Soccer League first
      division. The design of the study allowed a retrospective and prospective
      diagnosis of primary headaches according to the International Classification of
      Headache Disorders-II edition (ICHD-II), using anonymous questionnaires, which
      had to be filled out at regular times during the playing season. A total of 83
      athletes playing in four different clubs were involved; four of them changed
      football team during the season and so did not complete the study. During the
      championship three soccer players reported headache (3.6%) with features
      fulfilling ICHD-II criteria for episodic tension-type headache. Important and
      prolonged physical effort was reported as aggravating factor in one case, but no
      attacks occurred during competitive matches. The same athletes had reported a
      personal history of episodic tension-type headache. In conclusion, the occurrence
      of primary headaches among professional soccer players of Italian first division
      championship appear to be strikingly lower, as compared to that found in the
      general population. A possible explanation could be given by the selection
      operated by a career which is not compatible with unpredictable, disabling
      attacks.

PMID- 19169624
TI  - A rare cause of ischemic stroke: fibromuscular dysplasia.
AB  - Childhood ischemic stroke is uncommon and may be associated with many causes and
      require extensive evaluation. Fibromuscular dysplasia is a rare cause of unknown
      etiology of childhood stroke which is mostly related with renovascular
      hypertension and in adults about 85% of cases renal artery has been involved,
      whereas the intracerebral circulation is the main area affected in children and
      the documented cause of stroke. We report a 4-year-old girl who presented with
      facial paralysis and diagnosed as intracranial fibromuscular dysplasia without
      renal artery involvement.

PMID- 19169625
TI  - Economic evaluation of treating clinically isolated syndrome and subsequent
      multiple sclerosis with interferon beta-1b.
AB  - New therapeutic options have modified the natural history and health care costs
      of multiple sclerosis (MS). An epidemiological 25 years-long model-based cost
      utility analysis was performed following the Italian National Health Service
      (INHS) and societal perspectives to compare costs and quality-adjusted life years
      of treatment with Interferon beta-1b (IFNB-1b) from diagnosis of clinically
      isolated syndrome (CIS) versus treating at subsequent conversion to clinically
      definite MS (CDMS). Among patients treated (untreated) with IFNB-1b from CIS
      diagnosis, 40,420 (43,700) converted to CDMS after 25 years; the estimated
      cumulative probability of converting to CDMS during the first 3 years was 72.90%
      (84.94%) (P < 0.0001). Early treatment with IFNB-1b is highly cost-effective for
      the INHS (incremental cost-effectiveness ratio: Euros 2,574.94) and dominant from
      the societal viewpoint. Sensitivity analyses confirmed the base case findings.
      Early treatment with IFNB-1b delays conversion to CDMS in CIS patients and might
      be a "good value for money" health care programme.

PMID- 19169626
TI  - Trigeminal neuralgia as initial symptom of paramedian tentorial meningioma.
AB  - Posterior cranial fossa tumours, not involving the cerebellopontine angle
      cistern, are a rare cause of trigeminal neuralgia (TN). We describe a patient
      with a large paramedian tentorial meningioma associated with acquired Chiari
      malformation who presented with TN. Trigeminal pain resolved after gross total
      tumour resection and postoperative magnetic resonance images disclosed a minimal
      residual tumour in the torcular region as well as ascent of cerebellar tonsils.
      In this article, we investigate the physiopathological hypotheses for this
      unusual association with emphasis on the role of tonsillar prolapse as
      neuropathological basis of neuropathic pain in this patient.

PMID- 19169627
TI  - Subacute combined degeneration of the spinal cord caused by nitrous oxide
      anaesthesia.
AB  - Vitamin B12 deficiency causes haematological, gastrointestinal and neurological
      diseases. Subacute combined degeneration (SCD) of the spinal cord is
      characterised by degeneration of the posterior and lateral columns. We report a
      case of SCD associated with nitrous oxide anaesthesia.

PMID- 19169628
TI  - An atypical case of spontaneous intracranial hypotension.
AB  - Spontaneous intracranial hypotension (SIH) is a well-known clinical syndrome
      associated with the typical magnetic resonance imaging findings of pachymeningeal
      enhancement, downward cerebral displacement and subdural fluid collections.
      Atypical clinical presentations are not infrequent and often misdiagnosed. We
      report a case of SIH presenting with thunderclap headache and CT scan evocative
      of subarachnoid hemorrhage. We discuss the unusual presentation of this patient
      and the differential diagnosis of this case.

PMID- 19169629
TI  - Auditing physicians to improve their infection control behavior?

PMID- 19169630
TI  - Disseminated zoster in an elderly patient.
AB  - A 97-year-old lady was hospitalized for left leg cellulitis. Comorbidity included
      hypertension and congestive heart failure. While in hospital, she developed a
      painless vesicular rash localized to the territory of the left trigeminal nerve
      (third branch), which evolved to pustules and crusts (Figure 1). A chickenpox
      like disseminated eruption of vesicles followed within 4 days, with the same
      evolution pattern (Figure 2).The diagnosis of disseminated zoster was suspected.
      A PCR analysis confirmed the presence of varicella-zoster-virus (VZV) in an
      abdominal vesicle. The patient was treated with oral valacyclovir for 7 days.
      Clinical examination, laboratory tests (including HIV serology), and a chest
      radiograph revealed no evidence of underlying immunodeficiency or malignancy.

PMID- 19169631
TI  - Biomarkers of thrombosis, fibrinolysis, and inflammation in patients with severe
      sepsis due to community-acquired pneumonia with and without Streptococcus
      pneumoniae.
AB  - BACKGROUND: Severe Streptococcus pneumoniae (S. pneum) pneumonia has historically
      been associated with an acute presentation and increased mortality. Using data
      from patients with community-acquired pneumonia (CAP) and severe sepsis, we
      investigated: (1) the baseline patient characteristics and biomarkers of
      thrombosis, fibrinolysis, and inflammation in patients with CAP due to S. pneum
      infection (S. pneum CAP) or CAP due to infection with other or unidentified
      organisms (non-S. pneum CAP); (2) the behavior of these biomarkers over time and
      during treatment with drotrecogin alfa (activated) (DrotAA, recombinant activated
      protein C). PATIENTS AND METHODS: Data from the PROWESS (Recombinant Human
      Activated Protein C Worldwide Evaluation on Severe Sepsis) trial were
      retrospectively analyzed by treatment (DrotAA or placebo) in patients with CAP.
      RESULTS: Patients with S. pneum CAP (n = 157) tended to be younger and had fewer
      comorbid conditions than patients with non-S. pneum CAP (n = 445). Overall
      disease severity (median APACHE II scores) was not significantly different
      between the two groups at baseline. However, there were significant baseline
      differences in protein C and markers of coagulation, fibrinolysis, and
      inflammation. Although thrombosis markers were not different at baseline, D-dimer
      levels significantly increased from baseline to day 4 in placebo-treated patients
      with S. pneum compared to those with non-S. pneum. DrotAA treatment was
      associated with statistically significant improvements in protein C and markers
      of thrombosis in patients with S. pneum. In addition, the proportion of patients
      with severe protein C deficiency ( </= 40% activity) at baseline was
      significantly greater in patients with S. pneum than those with non-S. pneum.
      Among patients with S. pneum and severe protein C deficiency at baseline, a
      significantly greater proportion of patients were no longer severely protein C
      deficient after 4 days of DrotAA therapy. CONCLUSION: In this population of
      patients with severe sepsis, patients with S. pneum CAP had a more severe
      dysregulation of coagulation, fibrinolysis, and inflammation than patients with
      non-S. pneum CAP; the former also developed significantly elevated levels of
      markers of thrombosis. Treatment with DrotAA was associated with significant
      improvements in protein C levels as well as markers of thrombosis. These
      characteristics may make patients with S. pneum CAP and severe sepsis
      particularly suited to derive a benefit from therapy with DrotAA.

PMID- 19169632
TI  - Two different patterns of mutations are involved in the genotypic resistance
      score for atazanavir boosted versus unboosted by ritonavir in multiple failing
      patients.
AB  - OBJECTIVES: The protease inhibitor atazanavir (ATV) can be used either boosted by
      ritonavir (ATV300/r) or unboosted (ATV400). To date, however, genotypic
      resistance scores (GRSs) have been developed only for boosted-ATV. We have
      determined GRS associated with virologic response (VR) for both ATV300/r and
      ATV400 in highly pre-treated HIV-1 infected patients. PATIENTS AND METHODS: We
      analyzed the results of genotypic tests available 0-3 months before the
      initiation of an ATV-containing regimen in 159 patients with HIV-RNA >or= 500
      copies/ml (ATV300/r group: 74; ATV400 group: 85) who were enrolled in the CARe
      study through an Early Access Program. The impact of baseline protease mutations
      on VR (>or= 1 log(10)copies/ml HIV-RNA decrease at 12-24 weeks) was analyzed
      using Fisher's exact test. Mutated protease amino acid positions (MPP) with p <
      0.20 were retained for further analysis. The GRSs were determined by a step-by
      step analysis using the chi(2) test for trend. RESULTS: The GRSs for ATV300/r and
      ATV400 revealed differing sets of mutations. For ATV300/r, 12 MPPs (10C/I/V + 32I
      + 34Q + 46I/L + 53L + 54A/M/V + 82A/F/I/T + 84V + 90M - 15E/G/L/V -
      69K/M/N/Q/R/T/Y - 72M/ T/V; p = 1.38 x 10(-9)) were the most strongly associated
      with VR (VR: 100%, 78.3%, 83.3%, 75% and 0% of patients with a score of -2/-1, 0,
      1, 2, and >or= 3, respectively); the last three MPPs (I15/H69/I72) were
      associated with a better VR. For ATV400, nine MPPs (16E + 20I/M/R/T/V + 32I +
      33F/I/V + 53L/Y + 64L/M/ V + 71I/T/V + 85V + 93L/M; p = 9.42 x 10(-8)) were most
      strongly associated with VR (VR: 83.3%, 66.7%, 5.9%, 0% of patients with 0, 1/2,
      3, and >or= 4 MPP, respectively). Differences between GRSs for ATV300/r and
      ATV400 may be due to different ATV drug levels (boosted vs unboosted), favoring
      different pathways of escape from antiviral pressure. CONCLUSIONS: Both GRSs were
      independent predictors of response in a multivariable logistic regression model.
      Nevertheless, cross-validation of these GRSs on different patient databases is
      required before their implementation in clinical practice.

PMID- 19169633
TI  - Failure of current antibiotic first-line regimens and mortality in hospitalized
      patients with spontaneous bacterial peritonitis.
AB  - BACKGROUND: Increases in Gram-positive infections and infections with
      Enterobacteriaceae with antimicrobial resistance have been reported in patients
      with spontaneous bacterial peritonitis (SBP). This study was performed to
      investigate the rate of treatment failures of recommended empirical therapies and
      the impact on mortality. PATIENTS AND METHODS: A prospectively collected database
      comprising 101 patients with SBP (70 nosocomial, 31 community acquired) treated
      at a university hospital between 2002 and 2006 in Munich, Germany, was analyzed.
      RESULTS: 17 patients initially received a broader than recommended antibiotic
      regimen. Most of these were treated in the intensive care unit because of severe
      sepsis/septic shock. Hospital mortality in this group was 82%. A modification of
      therapy was necessary in 24 of the 84 patients receiving one of the published
      first-line therapies (cefotaxime, ampicillin/clavulanate, or ciprofloxacin).
      Mortality was significantly higher in these patients than in those with no change
      in treatment (66.7% vs 30%, p = 0.002). In 29 patients with positive cultures,
      mortality was also higher in those with an ineffective first-line treatment (90%
      vs 45%, p = 0.032). In the multivariable analysis, a modification of antibiotic
      treatment was an independent risk factor for mortality (odds ratio 5.876, 95%
      confidence interval 1.826-18.910, p = 0.003). In 41 culture-positive cases, the
      most commonly cultured pathogens were Escherichia coli (n = 17) and Enterococcus
      faecium (n = 10). Of the encountered bacterial microorganisms, 14 (33.3%) were
      resistant to cefotaxime, 17 (38.6%) were resistant to amoxicillin/clavulanate,
      and 19 (45.2%) were resistant to ciprofloxacin. 29 (64.4%) of the isolates were
      resistant to one of the recommended firstline antibiotic regimens, and 11 (24.4%)
      of the isolates were resistant to all three. CONCLUSION: Recommended empirical
      antibiotic regimens fail to achieve the desired effect in a substantial number of
      hospitalized patients with SBP. This has a negative impact on mortality.

PMID- 19169634
TI  - Hungarian hospital antibiotic consumption at the regional level, 1996-2005.
AB  - BACKGROUND: Regional variations in antibiotic consumption in outpatients have
      been reported previously, but nothing is as yet known about the regional
      distribution of antibiotic consumption in the hospital sector in Hungary. This
      study was designed to explore regional variations and investigate determinants of
      antibiotic consumption in hospital care in Hungary. MATERIALS AND METHODS:
      Regional distribution-based antibiotic sales data were obtained for a 10-year
      period (1996-2005) for the 20 Hungarian counties. Systemic antibacterial use
      (Anatomical Therapeutic Chemical code: J01) was expressed as the number of
      defined daily doses (DDD) per 100 patient-days. The multiple linear regression
      model was applied to investigate the determinants of regional differences in
      hospital antibiotic consumption. Independent variables related to health care
      access, utilization of hospital resources, doctors' workload, type of hospital
      care provided, and patient's characteristics and infections were considered as
      possible determinants, and data on these variables were obtained for 2 years
      (2004, 2005). We also tested the association between hospital and ambulatory care
      antibiotic consumption in Hungarian regions using the Pearson correlation test.
      RESULTS: For each year during the 1996-2005 study period, there were large and
      stable variations in total hospital antibiotic consumption (e.g., min-max(1996):
      16.0-28.2; min-max(2005): 15.2-32.2 DDD per 100 patient-days) depending on the
      region. In the two developed models (Model 1 and Model 2), the number of reported
      infections accounted for 53% of the observed regional variations in hospital
      antibiotic consumption (Model 1), and the number of reported infections together
      with the case-mix index were responsible for 61% (Model 2) . Total antibiotic
      consumption in hospitals showed a positive correlation (R = 0.71, p = 0.002) with
      total antibiotic consumption in ambulatory care. CONCLUSION: The case-mix index
      and the number of reported infections explained some of the observed regional
      variations. However, the moderate value of the models in explaining these
      regional variations suggest that determinants which could not be explored in this
      preliminary study may also contribute to regional differences. Future studies
      should aim at collecting data for each individual hospital as well as data on
      possible determinants for hospital antibiotic consumption.

PMID- 19169635
TI  - Outcome and predictive factors of mortality in hospitalized HIV-patients in
      Burkina Faso.
AB  - BACKGROUND: The aim of this study was to describe the clinical presentation and
      predictors of death in a HIV population hospitalized in Ouagadougou, Burkina
      Faso. MATERIALS AND METHODS: Baseline demographics, viro-immunological status,
      clinical presentations, and outcome have been analyzed by univariate analysis and
      a multivariate model. RESULTS: A total of 1,071 hospitalizations of HIV-positive
      patients was recorded between 1 January, 2004 and 31 August, 2006, the majority
      of whom were female (64.1%). The baseline CD4 cell count/microl was higher in the
      female patients than in the male ones (166.1 vs 110.9). Gastroenteric symptoms
      were the first cause of hospitalization (61.7%). The crude mortality rate was
      higher in males than females (38% vs 25.3%). Baseline World Health Organization
      clinical stage IV (OR 9.22), neurological syndrome (OR 3.04) or wasting syndrome
      at admission (OR 2.9), positive malaria film (OR 2.17), and an older age
      independently predicted death. Weight at admission > 40 kg and a higher platelet
      count at admission were independently associated with a better outcome.
      CONCLUSIONS: Females are admitted to hospital earlier than males, probably as an
      indirect result of the Prevention of Mother-to-Child Transmission (PMTCT) public
      health initiative. An active search of HIV status in other members of the family
      (PMTCT-plus) may result in the detection of asymptomatic HIV-infected patients as
      well. A Plasmodium falciparum-positive smear during admission significantly
      impacted on outcome as well as low platelet count.

PMID- 19169636
TI  - Evaluation of a particle gel immunoassay as a screening test for syphilis.
AB  - BACKGROUND: Recent trends in Western Europe show an increase in sexually
      transmitted infections. Surveillance data in Switzerland confirm this rising
      trend. Notifications of syphilis cases nearly doubled in the year 2002 and almost
      tripled in 2003. This trend necessitates an early correct diagnosis making
      reliable screening tests mandatory. MATERIALS AND METHODS: In the presented study
      a particle gel immunoassay (ID-PaGIA syphilis antibody test, Diamed) using
      recombinant treponemal antigens TpN15, TpN17 and TpN47 was evaluated as a
      screening test in comparison to the currently used Treponema pallidum particle
      agglutination test (Serodia-TPPA, Fujirebio). Serum samples were obtained from a
      cross-sectional sero-epidemiological study among men who have sex with men.
      Samples were tested with the PaGia and the TPPA. In the case of equivocal results
      a titrated TPPA of an external laboratory was used as a confirmation test.
      RESULTS: In total 650 serum samples (48 seropositive patients, 602 negative) were
      evaluated. The PaGIA showed a sensitivity of 0.89 (43/48) and the TPPA of 0.83
      (40/48). This difference was not statistically relevant (p = 0.4). The particle
      gel assay showed a significantly higher specificity (1.0) compared to the TPPA
      (0.98) (p = 0.004). CONCLUSION: The PaGIA showed a sensitivity comparable to that
      of other treponemal tests with an even better specificity. Advantages of the
      PaGIA are the fast reaction time of only 20 min and the simplicity of the
      procedure with minimal technical equipment.

PMID- 19169637
TI  - Influence of overjet and lip coverage on the prevalence and severity of incisor
      trauma.
AB  - OBJECTIVE: The aim of this study was to assess the influence of overjet size and
      lip coverage on the prevalence and severity of incisor trauma. PATIENTS AND
      METHODS: Dental records made on presentation of 1,367 patients were examined for
      data concerning the prevalence, type and severity of incisor trauma. Original
      overjet was measured on the pre-treatment study models and divided into two
      categories: normal overjet (0-3.0 mm) and increased overjet (> 3.0 mm). Lip
      coverage of the upper incisors was estimated with reference to photographs
      showing the patient's face and was then rated as adequate or inadequate. The
      patients were then divided into three groups: normal original overjet and
      adequate lip coverage (Group 1), increased original overjet and adequate lip
      coverage (Group 2), and increased original overjet and inadequate lip coverage
      (Group 3). RESULTS: Group 1 patients revealed a significantly lower prevalence of
      traumatic injuries than those in Group 2 (p = 0.028) or Group 3 (p = 0.003), and
      the odds ratios compared to Group 1 were 1.6634 for Group 2 and 2.0336 for Group
      3. Regarding the type of trauma, Group 3 patients showed a significantly higher
      frequency of periodontal injuries than those in Group 1 (p = 0.018) or Group 2 (p
      = 0.015). Furthermore, Group 3 patients had significantly more in juries to two
      or more teeth per person than patients in Group 1 (p < 0.001) or Group 2 (p <
      0.001). CONCLUSIONS: Increased overjet and inadequate lip coverage increase the
      risk and severity of incisor trauma. Early orthodontic treatment might prevent
      dental trauma in these patients.

PMID- 19169638
TI  - Corrosion susceptibility and nickel release of nickel titanium wires during
      clinical application.
AB  - BACKGROUND AND OBJECTIVE: Orthodontic wires are exposed to a corrosive intraoral
      environment and are subject to mechanical and thermal load. This could affect how
      nickel titanium (NiTi) wires corrode, as they possess temperature- and load
      dependent characteristics. It was the scope of this study to determine whether
      the clinical application of NiTi wires would lead to corrosion defects on the
      wire surfaces, and whether an influence on the patients' salivary Ni ion
      concentration would become apparent. MATERIAL AND METHODS: A total of 115 wires
      of different manufacturers (Forestadent Titanol 'Low Force' und 'Martensitic',
      Ormco Copper Ni-Ti 35 degrees C, Ortho Organizers NiTi) was retrieved after
      intraoral application lasting 1 to 12 months. The wires were examined after
      cleaning with a scanning electron microscope. We also analyzed the salivary Ni
      ion concentration in 18 patients at predefined intervals following a detailed
      orthodontic treatment protocol during the initial phase of orthodontic therapy.
      The intervals were: 1) a saliva sample before treatment commenced, 2) after
      bonding of brackets and bands, 3) 2 weeks after bonding, immediately before and
      4) immediately after fitting the archwires, and 5) 4 and 6) 8 weeks after placing
      the archwires. 16 to 20 brackets and bands were bonded in the upper and lower
      jaws, while NiTi leveling arches (ODS Euro Arch Opto Therm, 0.40 mm round) were
      fitted. The saliva samples were quick-frozen and subsequently dried under red
      light. Dried residuals were dissolved in aqua regia and filled up to 3 ml. The
      solutions were analyzed using a mass spectrometer (Perkin Elmer Elan 5000).
      RESULTS: Surface analysis revealed no differences in the degree of corrosion of
      the different products. In fact, we observed only extremely small and isolated
      corrosion defects. No statistically-significant differences were noted in the Ni
      ion concentration at time points 1 (reference value), 3, 5 and 6 (34, 34, 28 and
      30 microg/l, respectively). The samples taken immediately after bracket bonding
      or the NiTi wire application however displayed a significant increase in the
      salivary Ni ion concentration (2: 78 and 4: 56 microg/l). It was significantly
      higher after bonding of the steel brackets than after NiTi wire application.
      CONCLUSIONS: Increased Ni ions are released initially after the orthodontic
      devices have been fitted, but they decay quickly. This is reflected in miniscule
      corrosion defects as pitting. It is unlikely that orthodontic nickel titanium
      wires are a relevant additional Ni load for the patient.

PMID- 19169639
TI  - Morphometric analysis of facial profile in adults.
AB  - AIM: Are centroid size, principal component analysis (PCA) and thin-plate splines
      (TPS) sufficient for determining facial morphology? Is it possible to identify
      relationships between cranial morphology, gender and facial profile? MATERIAL AND
      METHODS: Profile photos of 110 adult patients were measured according to A.M.
      Schwarz landmarks using Onyx Ceph. Centroid size was calculated from x and y
      coordinates. After Procrustes transformation, a principal component analysis for
      identifying major components of facial morphology was performed and the results
      visualized using thin-plate splines. At the same time, lateral cephalograms of
      all patients were analyzed according to Hasund. RESULTS: There were significant
      differences in centroid size betweeen male and female patients. Only the vertical
      skeletal structure had an impact on centroid size. Six components (PC1 to PC6)
      were identified using PCA. They were responsible for 86.5% of the variance. PC1
      (33.9%) described scaling along an axis from Porion to chin. PC2 (28.6%)
      characterized the vertical dimensions of the lower face. Significant differences
      were only apparent between males and females in PC3 and PC4. In terms of
      cephalometric parameters, PC2 and PC3 differed in the vertical, and PC1 und PC2
      in the sagittal configuration. CONCLUSIONS: The analyses presented here suffice
      for describing facial morphology qualitatively and quantitatively as demonstrated
      by this example. Separating size from shape is useful for investigating
      therapeutically and growth-related morphological changes. It is difficult to draw
      conclusions about skeletal parameters.

PMID- 19169640
TI  - Dental side effects of mandibular advancement appliances - a 2-year follow-up.
AB  - BACKGROUND AND OBJECTIVES: Mandibular advancement appliances are employed in
      treating snoring and various forms of obstructive sleep apnea syndrome (OSAS).
      The splints facilitate the displacement of the mandible anteriorly and widens the
      pharyngeal lumen during sleep. Two-splint systems are anchored on the dental
      arches in the maxilla and mandible. The resulting reciprocal forces are
      transferred onto the teeth, leading to dental side effects when used long-term.
      We retrospectively examined the dental changes that occurred after patients had
      worn the Thornton Adjustable Positioner (TAP) for over two years. PATIENTS AND
      METHODS: We enrolled all patients consecutively in whom the diagnosis of OSAS was
      made following polysomnography in a sleep laboratory between January 2004 and
      December 2005 and who had been treated primarily with a TAP. We compared the
      patients' baseline findings with follow-up findings after more than 24 months of
      continuous appliance wear. RESULTS: 24/47 of the patients were still wearing the
      splints regularly after an average of 33 +/- 9.1 months. Overbite was highly
      significantly reduced (p = 0.006). We noted a reduction in the frontal overbite
      of more than 1 mm in ten patients (47.6%), and the overbite of one patient
      decreased by 4 mm. The maxillary front teeth showed significant palatal tipping
      and those in the mandible significant labial tipping. CONCLUSIONS: Clinically
      small but statistically significant dental side effects predominantly affecting
      the incisors' inclination occur after long-term wear of a TAP appliance. The
      clinical relevance of these dental changes to the patient can only be judged
      individually within the scope of an entire assessment.

PMID- 19169641
TI  - Quality development in a dental practice environment. A web-based system for
      measuring patient satisfaction.
AB  - OBJECTIVE: The aim of this study was to help orthodontic professionals to measure
      patient satisfaction objectively within their own clinical setting. We also aimed
      to share these benchmark data with an international audience. MATERIAL AND
      METHODS: The philosophy of the EURO-QUAL project was adopted, with 18
      orthodontists participating in this benchmarking project. We used the STOPS
      questionnaire tested on validity between 1998 and 2002. It consisted of 23
      statements measuring five dimensions of care and two open questions. Age and
      gender were collected as demographic data, and the respondents were anonymized.
      Either the internet or a paper version of the questionnaire was used for data
      collection. RESULTS: 1,538 patients responded during a 3-month period. When asked
      about the various dimensions of care, patients expressed satisfaction with the
      professional competence of their orthodontists and the treatment they received.
      Patients were least satisfied with the discomfort associated with the treatment
      and with the appointment procedures. The STOPS-questionnaire was further
      validated, revealing a Cronbach's Alpha score of 0.75. Average values for a
      benchmark were presented. CONCLUSIONS: Changes in society are always reflected in
      health care, therefore knowledge management is important. This study demonstrates
      a method for gaining explicit knowledge about patient satisfaction, which
      facilitates practice management and can be done quickly.

PMID- 19169642
TI  - A 57-year follow-up study of occlusion. Part 3: Oral health and attitudes to
      teeth among individuals with crossbite at the age of 8 years.
AB  - OBJECTIVE: To analyze occlusal changes occurring between the ages of 8 and 65
      years in persons with anterior and/or posterior crossbite at the age of 8; to
      examine their attitudes toward dental appearance and their experiences related to
      their own teeth. SAMPLE AND METHODS: Of the 81 people we contacted who had been
      documented as having crossbite as 8-year-olds in 1950, 21 agreed to participate
      in this follow-up study. Their occlusal conditions had been documented initially
      by intraoral photographs in 1950, and a clinical examination including facial
      photographs, further occlusal photographs and an interview took place in 2007.
      For comparison, we also had available similarly-documented examples of
      individuals (n = 18) of the same age and with normal occlusion in 1950. RESULTS:
      Oral hygiene was good or excellent in all individuals and all but one visited
      their dentist regularly. The average number of missing teeth was 3.8, whereas in
      the normal occlusion sample that number was 1.6. Of the eight persons who had
      undergone minor orthodontic treatment during childhood, five had an anterior
      crossbite resolved. Four persons who had initially presented a posterior
      crossbite later developed an anterior crossbite as well. In 2007, eleven
      individuals had a posterior and eight an anterior crossbite. At 65, four persons
      remembered that they had been teased in childhood because of their teeth, and
      could still remember the terms that had been used. Eighteen persons were
      satisfied with their teeth although two had severe anterior crossbite; three were
      dissatisfied, and their reasons were general health problems, mild crowding, and
      dentofacial asymmetry. Seven persons had TMJ symptoms with various types of
      history. With three exceptions, they all considered good tooth position to be
      important or very important. CONCLUSIONS: In those not orthodontically treated,
      malocclusion tended to worsen, although 18 of the 21 persons expressed
      satisfaction with their teeth as adults. They had a higher average number of
      missing teeth, and more had TMJ problems than the control group with normal
      occlusion.

PMID- 19169644
TI  - Isoliquiritigenin, from Dalbergia odorifera, up-regulates anti-inflammatory heme
      oxygenase-1 expression in RAW264.7 macrophages.
AB  - OBJECTIVES: Isoliquiritigenin (ISL), one of the major constituents of Dalbergia
      odorifera T. Chen (Leguminosae), is reported to exert anti-inflammatory effects,
      but the relevant anti-inflammatory mechanisms are not completely understood. Heme
      oxygenase-1 (HO-1) has been proven to be involved in the resolution of
      inflammatory responses. In this study, we investigated whether ISL could induce
      HO-1 expression in RAW264.7 macrophages, and if so, whether HO-1 could mediate
      the anti-inflammatory effects of ISL. METHODS: The protein expression of
      inducible nitric oxide synthase and HO-1 was analyzed by western blot analysis.
      The production of nitric oxide (NO) and interleukin-1beta (IL-1beta) and tumor
      necrosis factor-alpha (TNF-alpha) was assayed by Griess and ELISA, respectively.
      The TNF-alpha and HO-1 mRNA expression was analyzed by northern blot analysis.
      RESULTS: ISL markedly suppressed LPS-induced NO, IL-1beta, and TNF-alpha
      production. ISL induced HO-1 expression through the extracellular signal
      regulated kinase1/2 pathway in RAW264.7 macrophages. The effects of ISL on LPS
      induced NO and TNF-alpha production were reversed by the HO-1 inhibitor, tin
      protoporphyrin. CONCLUSIONS: ISL is an effective HO-1 inducer capable of
      inhibiting macrophage-derived inflammation.

PMID- 19169645
TI  - META060 inhibits multiple kinases in the NF-kappaB pathway and suppresses LPS-
      mediated inflammation in vitro and ex vivo.
AB  - OBJECTIVE: We investigated whether a novel candidate META060 targeted the
      inflammatory signal transduction without affecting constitutive COX-2 enzymatic
      activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We also
      investigated its bioavailability in humans and its anti-inflammatory effect ex
      vivo. METHODS: We measured prostaglandin E(2), nitric oxide, TNFalpha and IL-6 by
      ELISA, COX-2 protein by Western blot, NF-kappaB nuclear binding by
      electrophoretic mobility shift assays, and NF-kappaB activation by luciferase
      assay. Kinase inhibitions were measured by cell-free assays. Bioavailability was
      tested in 4 human subjects consuming 940 mg META060. LPS-activated TNFalpha and
      IL-6 were measured in peripheral blood mononuclear cells (PBMC) isolated from 1
      subject up to 6 hours post administration. RESULTS: META060 dose-dependently
      inhibited prostaglandin E(2) and nitric oxide formation, COX-2 abundance, and NF
      kappaB activation. In cell-free assays, META060 inhibited multiple kinases in the
      NF-kappaB signaling pathway, including BTK, PI3K, and GSK3. META060 was detected
      in the plasma of the subjects; isolated PBMC were resistant to LPS-stimulated
      TNFalpha and IL-6 production. CONCLUSION: Without inhibiting COX-2 enzyme,
      META060 reduces the inflammation by inhibiting multiple kinases involved in NF
      kappaB pathway, and may have potential as a safe anti-inflammatory therapeutic.

PMID- 19169646
TI  - Enhancement of activated beta1-integrin expression by prostaglandin E2 via EP
      receptors in isolated human coronary arterial endothelial cells: implication for
      the treatment of Kawasaki disease.
AB  - OBJECTIVE: Plasma prostaglandin E(2) (PGE(2)) levels are markedly elevated in
      acute Kawasaki disease (KD). We evaluated the function of the EP receptors in the
      expression of activated beta(1)-integrin stimulated by PGE(2) in human coronary
      arterial endothelial cells (HCAEC). METHODS: We determined the mRNA expression of
      the PGE(2) receptors, EP receptors (EP(1-4)) in HCAEC by RT-PCR and protein
      expression by Western blotting. We evaluated the function of the EP receptors in
      the expression of activated beta(1)-integrin stimulated by PGE(2) in HCAEC, using
      antagonists and agonists of the EP receptors, by flow cytometry. RESULTS: RT-PCR
      revealed mRNAs for all four EP receptors in HCAEC. Western blotting demonstrated
      EP(1), EP(2) and EP(3) expression in HCAEC. The EP(2) and EP(3) agonists enhanced
      the expression of activated beta(1)-integrin in HCAEC. The potency of the EP(2)
      agonist was significantly greater than that of the EP(3) agonist. Pretreatment
      with the EP(1), EP(2) and EP(3) antagonists inhibited the expression of activated
      beta(1)-integrin induced by PGE(2) in HCAEC. The potency of the EP(2) antagonist
      was significantly greater than that of the EP(1) and EP(3) antagonists.
      CONCLUSIONS: Our results suggest that PGE(2) mainly induces the activation of
      beta(1)-integrins via the EP(2) receptor in HCAEC. Our results further suggest
      that the EP(2) antagonist modulates the inflammatory response during KD
      vasculitis.

PMID- 19169647
TI  - Suramin inhibits macrophage activation by human group IIA phospholipase A2, but
      does not affect bactericidal activity of the enzyme.
AB  - OBJECTIVE: Suramin is a polysulphonated napthylurea antiprotozoal and
      anthelminitic drug, which also presents inhibitory activity against a broad range
      of enzymes. Here we evaluate the effect of suramin on the hydrolytic and
      biological activities of secreted human group IIA phospholipase A(2)
      (hsPLA(2)GIIA). MATERIALS AND METHODS: The hsPLA(2)GIIA was expressed in E. coli,
      and refolded from inclusion bodies. The hydrolytic activity of the recombinant
      enzyme was measured using mixed
      dioleoylphosphatidylcholine/dioleoylphosphatidylglycerol (DOPC/DOPG) liposomes.
      The activation of macrophage cell line RAW 264.7 by hsPLA(2) GIIA was monitored
      by NO release, and bactericidal activity against Micrococcus luteus was evaluated
      by colony counting and by flow cytometry using the fluorescent probe Sytox Green.
      RESULTS: The hydrolytic activity of the hsPLA(2) GIIA was inhibited by a
      concentration of 100 nM suramin and the activation of macrophages by hsPLA(2)
      GIIA was abolished at protein/suramin molar ratios where the hydrolytic activity
      of the enzyme was inhibited. In contrast, both the bactericidal activity of
      hsPLA(2) GIIA against Micrococcus luteus and permeabilization of the bacterial
      inner membrane were unaffected by suramin concentrations up to 50 microM.
      CONCLUSIONS: These results demonstrate that suramin selectively inhibits the
      activity of the hsPLA(2) GIIA against macrophages, whilst leaving the anti
      bacterial function unchanged.

PMID- 19169648
TI  - A new model of outbred genetically selected mice which present a strong acute
      inflammatory response in the absence of complement component C5.
AB  - OBJECTIVE: Mice selected for a strong (AIRmax) or weak (AIRmin) acute
      inflammatory response present different susceptibilities to bacterial infections,
      autoimmune diseases and carcinogenesis. Variations in these phenotypes have been
      also detected in AIRmax and AIRmin mice rendered homozygous for Slc11a1 resistant
      (R) and susceptible (S) alleles. Our aim was to investigate if the phenotypic
      differences observed in these mice was related to the complement system.
      MATERIAL: AIRmax and AIRmin mice and AIRmax and AIRmin groups homozygous for the
      resistance (R) or susceptibility (S) alleles of the solute carrier family 11a1
      member (Slc11a1) gene, formerly designated Nramp-1. METHODS AND RESULTS: While no
      difference in complement activity was detected in sera from AIRmax and AIRmin
      strains, all sera from AIRmax Slc11a1 resistant mice (AIRmax(RR)) presented no
      complement-dependent hemolytic activity. Furthermore, C5 was not found in their
      sera by immunodiffusion and, polymerase chain reaction and DNA sequencing of its
      gene demonstrated that AIRmax(RR) mice are homozygous for the C5 deficient (D)
      mutation previously described in A/J. Therefore, the C5D allele was fixed in
      homozygosis in AIRmax(RR) line. CONCLUSIONS: The AIRmax(RR) line is a new
      experimental mouse model in which a strong inflammatory response can be triggered
      in vivo in the absence of C5.

PMID- 19169649
TI  - Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory
      mediators by inhibiting NF-kB.
AB  - OBJECTIVE: Sivelestat sodium hydrate (sivelestat) is a specific synthetic
      inhibitor of neutrophil elastase (NE). Various studies suggest that sivelestat
      treatment reduces inflammation. In this study, we tested the hypothesis that
      sivelestat acts as an inhibitor of inflammatory mediators and prevents nuclear
      factor-kB (NF-kB) activation. METHODS: In the presence and absence of sivelestat,
      the mouse macrophage cell line RAW 264.7 was stimulated with lipopolysaccharide
      (LPS) and the levels of inflammatory mediators (TNF-alpha, IL-6 and high mobility
      group box 1 (HMGB1)) and nitrite in the cell supernatant were measured, along
      with inducible nitric oxide synthase (iNOS) expression. RESULTS: While LPS
      administration increased the secretion of inflammatory mediators and nitric oxide
      (NO), sivelestat decreased the secretion of these mediators. Cell signaling
      studies demonstrated that sivelestat decreased NF-kB activation by inhibiting IkB
      phosphorylation. CONCLUSION: Sivelestat may inhibit the various inflammatory
      mediators through NF-kB inhibition.

PMID- 19169650
TI  - Helicobacter pylori induces the release of alpha-defensin by human granulocytes.
AB  - OBJECTIVES: Little information is available on the potential role of alpha
      defensins derived from neutrophils during H. pylori infection, or the effect of
      H. pylori on the alpha-defensin release. The effects of H. pylori on human
      granulocytes were investigated in vitro by flow cytometry and ELISA. Additionally
      we sought to identify by immunohistochemistry the alpha-defensins within the
      gastric mucosa of patients infected with H. pylori. MATERIALS AND METHODS: The
      intracellular expression of alpha-defensin in human granulocytes and in
      mononuclear cells was determined by flow cytometry. Induction of alpha-defensin
      release from granulocytes, mononuclear cells, or from whole blood cultures by H.
      pylori was detected by measuring the HNP1-3 (alpha-defensin) concentrations in
      the supernatants by ELISA. Immunohistochemistry was used to identify HNP1-3 in
      infiltrating neutrophils in the gastric mucosa of eight patients. RESULTS: A
      considerable intracellular alpha-defensin staining was observed in granulocytes.
      Stimulation of granulocytes with H. pylori resulted in a decrease in
      intracellular staining which was due to the extracellular release of alpha
      defensin. In whole blood cultures H. pylori infection resulted in significantly
      high alpha-defensin concentrations (131623 +/- 13986 pg/ml), which were mainly
      due to the activity of the granulocytes with only a minor amount furnished by the
      mononuclear cells. In H. pylori-infected mucosa, infiltrating neutrophils showed
      intense immunostaining with anti-HNP1-3. The intensity of alpha-defensin staining
      varied parallel with the density of H. pylori in the biopsy samples. CONCLUSIONS:
      H. pylori induce alpha-defensin release from granulocytes which may well be
      important in local host response to H. pylori infection in gastroduodenal
      diseases.

PMID- 19169652
TI  - Prediction of subcellular localization of apoptosis protein using Chou's pseudo
      amino acid composition.
AB  - Apoptosis proteins play an essential role in regulating a balance between cell
      proliferation and death. The successful prediction of subcellular localization of
      apoptosis proteins directly from primary sequence is much benefited to understand
      programmed cell death and drug discovery. In this paper, by use of Chou's pseudo
      amino acid composition (PseAAC), a total of 317 apoptosis proteins are predicted
      by support vector machine (SVM). The jackknife cross-validation is applied to
      test predictive capability of proposed method. The predictive results show that
      overall prediction accuracy is 91.1% which is higher than previous methods.
      Furthermore, another dataset containing 98 apoptosis proteins is examined by
      proposed method. The overall predicted successful rate is 92.9%.

PMID- 19169651
TI  - Safety and feasibility of switching from phenytoin to levetiracetam monotherapy
      for glioma-related seizure control following craniotomy: a randomized phase II
      pilot study.
AB  - Seizures are common in patients with gliomas, and phenytoin (PHT) is frequently
      used to control tumor-related seizures. PHT, however, has many undesirable side
      effects (SEs) and drug interactions with glioma chemotherapy. Levetiracetam (LEV)
      is a newer antiepileptic drug (AED) with fewer SEs and essentially no drug
      interactions. We performed a pilot study testing the safety and feasibility of
      switching patients from PHT to LEV monotherapy for postoperative control of
      glioma-related seizures. Over a 13-month period, 29 patients were randomized in a
      2:1 ratio to initiate LEV therapy within 24 h of surgery or to continue PHT
      therapy. 6 month follow-up data were available for 15 patients taking LEV and for
      8 patients taking PHT. In the LEV group, 13 patients (87%) were seizure-free. In
      the PHT group, 6 patients (75%) were seizure-free. Reported SEs at 6 months was
      as follows (%LEV/%PHT group): dizziness (0/14), difficulty with coordination
      (0/29), depression (7/14) lack of energy or strength (20/43), insomnia (40/43),
      mood instability (7/0). The pilot data presented here suggest that it is safe to
      switch patients from PHT to LEV monotherapy following craniotomy for
      supratentorial glioma. A large-scale, double-blinded, randomized control trial of
      LEV versus PHT is required to determine seizure control equivalence and better
      assess differences in SEs.

PMID- 19169653
TI  - Iron-dependent oxidative inactivation with affinity cleavage of pyruvate kinase.
AB  - Treatment of rabbit muscle pyruvate kinase with iron/ascorbate caused an
      inactivation with the cleavage of peptide bond. The inactivation or fragmentation
      of the enzyme was prevented by addition of Mg2+, catalase, and mannitol, but ADP
      and PEP the substrates did not show any effect. Protective effect of catalase and
      mannitol suggests that hydroxyl radical produced through the ferrous ion
      dependent reduction of oxygen is responsible for the inactivation/fragmentation
      of the enzyme. SDS-PAGE and TOF-MS analysis confirmed five pairs of fragments,
      which were determined to result from the cleavage of the Lys114-Gly115, Glu117
      Ile118, Asp177-Gly178, Gly207-Val208, and Phe243-Ile244 bonds of the enzyme by
      amino-terminal sequencing analysis. Protection of the enzyme by Mg2+ implies the
      identical binding sites of Fe2+ and Mg2+, but the cleavage sites were
      discriminated from the cofactor Mg2+-binding sites. Considering amino acid
      residues interacting with metal ions and tertiary structure, Fe2+ ion may bind to
      Asp177 neighboring to Gly207 and Glu117 neighboring to Lys114 and Phe243, causing
      the peptide cleavage by hydroxyl radical. Iron-dependent oxidative
      inactivation/fragmentation of pyruvate kinase can explain the decreased
      glycolytic flux under aerobic conditions. Intracellular free Mg2+ concentrations
      are responsible for the control of cellular respiration and glycolysis.

PMID- 19169654
TI  - Coordinated and tailored work rehabilitation: a randomized controlled trial with
      economic evaluation undertaken with workers on sick leave due to musculoskeletal
      disorders.
AB  - INTRODUCTION: In Denmark, the magnitude and impact of work disability on the
      individual worker and society has prompted the development of a new "coordinated
      and tailored work rehabilitation" (CTWR) approach. The aim of this study was to
      compare the effects of CTWR with conventional case management (CCM) on return-to
      work of workers on sick leave due to musculoskeletal disorders (MSDs). METHODS:
      The study was a randomized controlled trial with economic evaluation undertaken
      with workers on sick leave for 4-12 weeks due to MSDs. CTWR consists of a work
      disability screening by an interdisciplinary team followed by the collaborative
      development of a RTW plan. The primary outcome variable was registered cumulative
      sickness absence hours during 12 months follow-up. Secondary outcomes were work
      status as well as pain intensity and functional disability, measured at baseline,
      3 and 12 months follow-up. The economic evaluation (intervention costs,
      productivity loss, and health care utilization costs) was based on administrative
      data derived from national registries. RESULTS: For the time intervals 0-6
      months, 6-12 months, and the entire follow-up period, the number of sickness
      absence hours was significantly lower in the CTWR group as compared to the
      control group. The total costs saved in CTWR participants compared to controls
      were estimated at US $ 1,366 per person at 6 months follow-up and US $ 10,666 per
      person at 12 months follow-up. CONCLUSIONS: Workers on sick leave for 4-12 weeks
      due to MSD who underwent "CTWR" by an interdisciplinary team had fewer sickness
      absence hours than controls. The economic evaluation showed that-in terms of
      productivity loss-CTWR seems to be cost saving for the society.

PMID- 19169656
TI  - [Surgical treatment of musculoskeletal soft tissue sarcomas].
AB  - Treatment of soft tissue sarcomas requires an individual plan which considers
      interdisciplinary recommendations and the various clinical situations. Anatomical
      region, histological grading and typing, and tumor size necessitate adjusted
      methods of reconstruction. The biopsy should be performed at the institution
      where the patient is treated. In general surgical resection of the tumor will be
      the treatment of choice. Adjuvant therapies are applied according to anatomical
      region and size and grading of the tumor. Surgery alone is recommended only in
      small (<5 cm), superficial, low-grade sarcomas. Sarcomas larger than 5 cm in
      diameter should be treated by surgery and radiotherapy, achieving excellent
      results, although in high-grade sarcomas more than 50% of patients still will
      experience metastatic disease. In case of locally recurrent disease, surgical
      revision with tumor-free resection margins followed by radiotherapy should be the
      aim. This applies even for patients who had had radiotherapy after the first
      excision. In this case brachytherapy is a good modality of tissue-sparing
      treatment.

PMID- 19169657
TI  - From furless to heartless-unraveling the diverse functions of cathepsin L.

PMID- 19169658
TI  - [Use of zolpidem and zopiclone on private prescriptions between 1993 and 2007].
AB  - OBJECTIVE: Aim of this study was to analyse the amount of so-called private
      prescriptions of zolpidem and zopiclone (Z drugs) over a 15-year period in
      Germany. Any doctor can prescribe drugs privately. Private prescriptions are
      fully funded by the patients. At present the total number of doctors'
      prescriptions in Germany is undocumented because this information is not recorded
      in insurance claims data. This may be one reason why physicians prescribe drugs
      that are associated with abuse and dependence (such as Z drugs) more frequently
      on private prescriptions. METHODS: We compared utilization data from statutory
      health insurance claims with the purchasing statistics from public pharmacies
      over the years 1993-2007. RESULTS: Throughout the study period, purchases of
      zolpidem and zopiclone increased from 1.4 million to 3.7 million packages and 0.8
      million to 3.9 million packages, respectively. A constantly rising proportion of
      private prescriptions for zolpidem resp. zopiclone were issued between 1993 (+6%
      resp. +6%), 1999 (+43% resp. +34%), and 2007 (+122% resp. +72%). CONCLUSION:
      Since their approval in Germany, zopiclone and especially zolpidem have
      frequently been dispensed on private prescriptions.

PMID- 19169659
TI  - [Urinary diversions: which one one is right for which patient?].
AB  - Standardized operating techniques and surgeons' experiences have contributed to
      the development of complex urinary diversion systems over the last two decades.
      Patients' desires and comorbidity risks, such as kidney or bowel dysfunction, as
      well as their mental and manual abilities need to be taken into account. Careful
      preoperative decision making is essential if patients are to accept the chosen
      urinary diversion system and improve their quality of life. Ileal and ileocecal
      orthotopic neobladders have proven to be effective and comfortable for long-time
      use, thus stimulating decisions for orthotopic bladder substitution despite the
      risk of incontinence episodes, especially during the night. Catheterization of
      continent reservoirs connected to the umbilicus (e.g., ileocecal reservoirs,
      Mainz pouch I) are widely accepted as an alternative diversion procedure if the
      urethra and/or sphincter region have to be removed. The patient's desire to avoid
      a wet stoma and achieve a cosmetically "unchanged" body image is met by these
      urinary diversion techniques. The surgeon's experience and the patient's mental
      and general health status must be considered in order to meet the increased
      complexity of these specific urinary diversions. Nevertheless, elderly patients
      often tend to prefer an ileal conduit as the easiest solution for urinary
      diversion. Therefore, even in experienced urological departments, the percentage
      of patients with orthotopic or self-catheterizable bladder substitution ranges
      between 30% and 66%, while the ileal conduit is selected in up to 64% of cases
      after cystectomy. The future of laparoscopic cystectomy has just begun and will
      affect future techniques of urinary diversion.

PMID- 19169660
TI  - [Extending the limits of lymphadenectomy during radical cystectomy: pitfalls in
      the interpretation of contemporary study results].
AB  - The optimal extent of lymphadenectomy performed during radical cystectomy for
      transitional cell carcinoma of the bladder is currently under intensive debate.
      Extending the limits of lymphadenectomy has been hypothesized to add further
      diagnostic and therapeutic benefit. However, our current knowledge is based
      exclusively on results from retrospective studies that are hampered by several
      statistical shortcomings. This article provides a critical analysis of the
      contemporary data on the subject and outlines typical statistical pitfalls that
      must be considered when interpreting such research results.

PMID- 19169661
TI  - Molecular variation among Chinese and global winter faba bean germplasm.
AB  - A sample of winter faba bean germplasm from China was compared with germplasm
      from outside China, using AFLP analyses. Both sets of germplasm were obtained
      from the National Genebank of China, Institute of Crop Sciences (ICS), Chinese
      Academy of Agricultural Sciences, Beijing, China. A sample of 39 winter type
      accessions from outside of China and 204 Chinese landraces and varieties (201
      winter types and 3 spring types) were characterized with 10 AFLP primers. These
      detected 266 polymorphic bands. The Chinese germplasm was clearly separated from
      the rest of the world in principal component analysis and clustering analysis,
      with the spring types from China showing the greatest separation. Yunnan
      germplasm, both landraces and commercial varieties, showed the greatest
      separation among the germplasm of Chinese winter faba bean provinces. The
      landraces/varieties from Anhui, Zhejiang, Sichuan, Jianxi, Guizhou and Fujian
      provinces clustered in a central group.

PMID- 19169662
TI  - A simple two-step protocol for the purification of human pancreatic beta cells.
AB  - AIMS/HYPOTHESIS: Isolated pure human beta cells would be helpful for a number of
      research purposes. However, lack of beta cell-specific surface antigens has been
      a major problem. We aimed to develop a simple method for human beta cell
      isolation based on the initial elimination of ductal cells by their expression of
      carbohydrate antigen 19-9 (CA19-9), followed by positive selection of beta cells
      by their expression of polysialic acid-neural cell adhesion molecule (PSA-NCAM).
      METHODS: Cell type-specific expression of CA19-9, NCAM and PSA-NCAM was studied
      in sections of adult human pancreas and in cultured primary endocrine and
      exocrine cells. Dispersed human islet cells were purified in two steps, after 4
      days of suspension culture, by binding to magnetic microbeads coupled to
      antibodies against CA19-9 and PSA-NCAM. RESULTS: NCAM expression was detected in
      ducts and islets in the human pancreas. In contrast, PSA-NCAM immunoreactivity
      was detected only in islets. PSA-NCAM staining in dispersed cells revealed that
      the marker is expressed in all endocrine cell types, but not in duct cells.
      Purification of dispersed islet cells using PSA-NCAM microbeads alone did not
      completely eliminate contaminating duct cells. However, elimination of the duct
      cells by CA19-9 microbeads followed by positive sorting of the PSA-NCAM-positive
      cells in five consecutive islet preparations resulted in 90 to 98% pure endocrine
      cells, of which 89 to 97% were beta cells. CONCLUSIONS/INTERPRETATION: We
      describe a simple and reproducible method for purification of viable human
      pancreatic beta cells devoid of exocrine acini and ducts.

PMID- 19169663
TI  - Beneficial effects of leptin on glycaemic and lipid control in a mouse model of
      type 2 diabetes with increased adiposity induced by streptozotocin and a high-fat
      diet.
AB  - AIMS/HYPOTHESIS: We have previously demonstrated the therapeutic usefulness of
      leptin in lipoatrophic diabetes and insulin-deficient diabetes in mouse models
      and could also demonstrate its dramatic effects on lipoatrophic diabetes in
      humans. The aim of the present study was to explore the therapeutic usefulness of
      leptin in a mouse model of type 2 diabetes with increased adiposity. METHODS: To
      generate a mouse model mimicking human type 2 diabetes with increased adiposity,
      we used a combination of low-dose streptozotocin (STZ, 120 microg/g body weight)
      and high-fat diet (HFD, 45% of energy as fat). Recombinant mouse leptin was
      infused chronically (20 ng [g body weight](-1) h(-1)) for 14 days using a mini
      osmotic pump. The effects of leptin on food intake, body weight, metabolic
      variables, tissue triacylglycerol content and AMP-activated protein kinase (AMPK)
      activity were examined. RESULTS: Low-dose STZ injection led to a substantial
      reduction of plasma insulin levels and hyperglycaemia. Subsequent HFD feeding
      increased adiposity and induced insulin resistance and further augmentation of
      hyperglycaemia. In this model mouse mimicking human type 2 diabetes (STZ/HFD),
      continuous leptin infusion reduced food intake and body weight and improved
      glucose and lipid metabolism with enhancement of insulin sensitivity. Leptin also
      decreased liver and skeletal muscle triacylglycerol content accompanied by an
      increase of alpha2 AMPK activity in skeletal muscle. Pair-feeding experiments
      demonstrated that leptin improved glucose and lipid metabolism independently of
      the food intake reduction. CONCLUSIONS/INTERPRETATION: This study demonstrates
      the beneficial effects of leptin on glycaemic and lipid control in a mouse model
      of type 2 diabetes with increased adiposity, indicating the possible clinical
      usefulness of leptin as a new glucose-lowering drug in humans.

PMID- 19169665
TI  - New evidence for Otzi's final trauma.

PMID- 19169664
TI  - Pioglitazone stimulates AMP-activated protein kinase signalling and increases the
      expression of genes involved in adiponectin signalling, mitochondrial function
      and fat oxidation in human skeletal muscle in vivo: a randomised trial.
AB  - AIMS/HYPOTHESIS: The molecular mechanisms by which thiazolidinediones improve
      insulin sensitivity in type 2 diabetes are not fully understood. We hypothesised
      that pioglitazone would activate the adenosine 5'-monophosphate-activated protein
      kinase (AMPK) pathway and increase the expression of genes involved in
      adiponectin signalling, NEFA oxidation and mitochondrial function in human
      skeletal muscle. METHODS: A randomised, double-blind, parallel study was
      performed in 26 drug-naive type 2 diabetes patients treated with: (1)
      pioglitazone (n = 14) or (2) aggressive nutritional therapy (n = 12) to reduce
      HbA(1c) to levels observed in the pioglitazone-treated group. Participants were
      assigned randomly to treatment using a table of random numbers. Before and after
      6 months, patients reported to the Clinical Research Center of the Texas Diabetes
      Institute for a vastus lateralis muscle biopsy followed by a 180 min euglycaemic
      hyperinsulinaemic (80 mU m(-2) min(-1)) clamp. RESULTS: All patients in the
      pioglitazone (n = 14) or nutritional therapy (n = 12) group were included in the
      analysis. Pioglitazone significantly increased plasma adiponectin concentration
      by 79% and reduced fasting plasma NEFA by 35% (both p < 0.01). Following
      pioglitazone, insulin-stimulated glucose disposal increased by 30% (p < 0.01),
      and muscle AMPK and acetyl-CoA carboxylase (ACC) phosphorylation increased by 38%
      and 53%, respectively (p < 0.05). Pioglitazone increased mRNA levels for
      adiponectin receptor 1 and 2 genes (ADIPOR1, ADIPOR2), peroxisome proliferator
      activated receptor gamma, coactivator 1 gene (PPARGC1) and multiple genes
      involved in mitochondrial function and fat oxidation. Despite a similar reduction
      in HbA(1c) and similar improvement in insulin sensitivity with nutritional
      therapy, there were no significant changes in muscle AMPK and ACC
      phosphorylation, or the expression of ADIPOR1, ADIPOR2, PPARGC1 and genes
      involved in mitochondrial function and fat oxidation. No adverse (or unexpected)
      effects or side effects were reported from the study.
      CONCLUSIONS/INTERPRETATIONS: Pioglitazone increases plasma adiponectin levels,
      stimulates muscle AMPK signalling and increases the expression of genes involved
      in adiponectin signalling, mitochondrial function and fat oxidation. These
      changes may represent an important cellular mechanism by which thiazolidinediones
      improve skeletal muscle insulin sensitivity. TRIAL REGISTRATION: NCT 00816218
      FUNDING: This trial was funded by National Institutes of Health Grant DK24092, VA
      Merit Award, GCRC Grant RR01346, Executive Research Committee Research Award from
      the University of Texas Health Science Center at San Antonio, American Diabetes
      Association Junior Faculty Award, American Heart Association National Scientist
      Development Grant, Takeda Pharmaceuticals North America Grant and Canadian
      Institute of Health Research Grant.

PMID- 19169666
TI  - Interest of an objective evaluation of cough during weaning from mechanical
      ventilation.
AB  - PURPOSE: This study aimed to evaluate an objective measure of cough strength, the
      peak cough expiratory flow (PCEF), as a predictive criterion of success or
      failure of extubation. METHODS: Patients under mechanical ventilation for more
      than 24 h who successfully passed the spontaneous breathing trial were included
      in the study. Just before extubation, PCEF was measured with an electronic
      flowmeter. RESULTS: A total of 130 patients were included. The median duration of
      mechanical ventilation before extubation was 8 days (4-17). Fourteen patients
      (10.8%) failed extubation. The sole factor significantly associated with
      extubation failure was the measure of PCEF. The patients who did not cough at
      order had a higher rate of extubation failure than those who did (P = 0.03). The
      mean PCEF of patients who failed extubation (36.3 +/- 15 l/min) was significantly
      lower than the one of patients who succeeded (63.6 +/- 32 l/min) (P < 0.001). The
      optimal cut-off value of PCEF was 35 l/min. Overall, an inability to cough at
      order or a PCEF < or =35 l/min predicted extubation failure with a sensitivity of
      79% and a specificity of 71%. The risk of extubation failure was 24% for the
      patients who did not cough at order or with a PCEF < or =35 l/min and 3.5% for
      those with a PCEF >35 l/min [RR = 6.9 (95% CI, 2-24); P = 0.002]. CONCLUSIONS:
      This study confirmed the interest of measuring the PCEF to predict extubation
      outcome in patients having successfully passed the spontaneous breathing trial.

PMID- 19169667
TI  - An improved Boussignac device for the delivery of non-invasive CPAP: the SUPER
      Boussignac.
AB  - PURPOSE: The purpose of this study is to describe and test a modified Boussignac
      system for non-invasive continuous positive airway pressure, aimed at reducing
      the decrease in inspiratory oxygen fraction (FiO(2)) with higher inspiratory peak
      flow rates. METHODS: We modified a Boussignac circuit by inserting a T-piece
      between the Boussignac valve and the face mask. The T-piece was connected to a
      reservoir balloon receiving oxygen by an independent source. The system was
      tested in a bench study, consisting of five steps, with increasing inspiratory
      peak flow rates (V(insp)) Three levels of PEEP were tested: 7, 10 and 13 cmH(2)O.
      The following devices were tested: Boussignac, Boussignac with reservoir but
      without supplementary oxygen, Boussignac with reservoir and 10 (SUPER
      Boussignac(10)) and 30 l/min (SUPER-Boussignac(30)) of supplementary oxygen. In
      each step we measured FiO(2), tidal volumes, and airway pressure. RESULTS: FiO(2)
      increased with PEEP and decreased at increasing V(insp) with all the systems.
      However, FiO(2) increased with SUPER-Boussignac(10) (7-10%) and with SUPER
      Boussignac(30) (10-30%). Moreover, in the latter case, for V(insp) values up to
      60 l/min, FiO(2) became independent of V(insp). The SUPER-Boussignac allowed also
      smaller drop in airway pressure during inspiration and higher tidal volumes.
      CONCLUSIONS: The SUPER-Boussignac represents a simple way to significantly
      improve the performance of the Boussignac device.

PMID- 19169668
TI  - Is C-reactive protein a good prognostic marker in septic patients?
AB  - RATIONALE: Several studies have shown that C-reactive protein (CRP) is a marker
      of infection. The aim of this study was to evaluate CRP as marker of prognosis
      outcome in septic patients and to assess the correlation of CRP with severity of
      sepsis. METHODS: During a 14-month period, we prospectively included all patients
      with sepsis admitted to an intensive care unit (ICU). Patients were categorized
      into sepsis, severe sepsis and septic shock. Acute Physiology and Chronic Health
      Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II,
      Sequential Organ Failure Assessment (SOFA) score, CRP, body temperature and white
      cell count (WCC) of the day of sepsis diagnosis were collected. RESULTS: One
      hundred and fifty-eight consecutive septic patients (mean age 59 years, 98 men,
      ICU mortality 34%) were studied. The area under the receiver operating
      characteristics curves of APACHE II, SAPS II, SOFA, CRP, body temperature and WCC
      as prognostic markers of sepsis were 0.75 [95% confidence interval (CI) 0.67
      0.83], 0.82 (95% CI 0.75-0.89), 0.8 (95% CI 0.72-0.88), 0.55 (95% CI 0.45-0.65),
      0.48 (95% CI 0.38-0.58) and 0.46 (95% CI 0.35-0.56), respectively. In the
      subgroup of patients with documented sepsis we obtained similar results. The ICU
      mortality rate of septic patients with CRP < 10, 10-20, 20-30, 30-40 and >40
      mg/dL was 20, 34, 30.8, 42.3 and 39.1%, respectively (P = 0.7). No correlation
      was found between CRP concentrations and severity of sepsis. CONCLUSIONS: In
      septic patients, CRP of the day of sepsis diagnosis is not a good marker of
      prognosis.

PMID- 19169669
TI  - Acute renal failure due to severe rhabdomyolysis: a rare clinical manifestation
      of atrial myxoma.

PMID- 19169670
TI  - A small heat-shock protein confers stress tolerance and stabilizes thylakoid
      membrane proteins in cyanobacteria under oxidative stress.
AB  - Small heat-shock proteins are molecular chaperones that bind and prevent
      aggregation of nonnative proteins. They also associate with membranes. In this
      study, we show that the small heat-shock protein HspA plays a protective role
      under oxidative stress in the cyanobacterium Synechococcus elongatus strain ECT16
      1, which constitutively expresses HspA. Compared with the reference strain ECT,
      ECT16-1 showed much better growth and viability in the presence of hydrogen
      peroxide. Under the peroxide stress, pigments in thylakoid membrane, chlorophyll,
      carotenoids, and phycocyanins, were continuously reduced in ECT, but in ECT16-1
      they decreased only during the first 24 h of stress; thereafter no further
      reduction was observed. For comparison, we analyzed a wild type and an hspA
      deletion strain from Synechocystis sp. PCC 6803 and found that lack of hspA
      significantly affected the viability of the cell and the pigment content in the
      presence of methyl viologen, suggesting that HspA stabilizes membrane proteins
      such as the photosystems and phycobilisomes from oxidative damage. In vitro pull
      down assays showed a direct interaction of HspA with components of
      phycobilisomes. These results show that HspA and small heat-shock proteins in
      general play an important role in the acclimation to oxidative stress in
      cyanobacteria.

PMID- 19169671
TI  - Drug context differently regulates cocaine versus heroin self-administration and
      cocaine- versus heroin-induced Fos mRNA expression in the rat.
AB  - RATIONALE: We have previously reported that cocaine self-administration is
      facilitated in male rats not residing in the test chambers (Non Resident rats)
      relative to rats living in the test chambers at all times (Resident rats).
      Surprisingly, the opposite was found for heroin. MATERIALS AND METHODS: We
      predicted that, when given access to both cocaine and heroin on alternate days,
      Non Resident rats would take more cocaine relative to heroin than Resident rats.
      Heroin (25.0 microg/kg) and cocaine (400 microg/kg), were made alternately
      available for 14 self-administration sessions, on a fixed ratio (FR) schedule
      that was progressively increased from FR1 to FR5. Next, some rats underwent a
      progressive-ratio procedure for heroin and cocaine. The other rats continued to
      alternate heroin and cocaine self-administration for 12 additional sessions,
      during which the FR schedule was progressively increased from FR10 to FR100. The
      second aim of the study was to investigate Fos mRNA expression in Resident and
      Non Resident rats treated with non-contingent intravenous infusion of "self
      administration doses" of heroin (25.0 microg/kg) and cocaine (400 microg/kg).
      RESULTS: We found that: (1) drug-taking context differentially modulates
      intravenous cocaine versus heroin self-administration; (2) very low doses of
      cocaine and heroin are sufficient to induce Fos mRNA expression in the posterior
      caudate; (3) drug-administration context differentially modulates cocaine- versus
      heroin-induced Fos mRNA expression. CONCLUSIONS: Our study indicates that the
      context of drug taking can play a powerful role in modulating cocaine versus
      heroin intake in the laboratory rat.

PMID- 19169672
TI  - Caffeine and a selective adenosine A2A receptor antagonist induce reward and
      sensitization behavior associated with increased phospho-Thr75-DARPP-32 in mice.
AB  - RATIONALE: Caffeine, an antagonist of adenosine A(1) and A(2A) receptor, is the
      most widely used psychoactive substance in the world. Evidence indicates that
      caffeine interacts with the neuronal systems involved in drug reinforcing.
      Although adenosine A(1) and/or A(2A) receptor have been found to play important
      roles in the locomotor stimulation and probably reinforcing effect of caffeine,
      the relative contribution of the A(1) and/or A(2A) receptors to the acute and
      chronic motor activation and reinforcing effects of caffeine has not been
      completely investigated. OBJECTIVE: The roles of adenosine A(1) and/or A(2A)
      receptor and the association of phospho-Thr75-dopamine- and cAMP-regulated
      phosphoprotein of molecular weight 32 kDa (DARPP-32) in the motor activation and
      reinforcing effects of caffeine, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a
      selective A(1) antagonist, and 5-amino-7-(beta-phenylethyl)-2-(8-furyl) pyrazolol
      [4,3-e]-1,2,4-triazolol [1,5-c] pyrimidine (SCH58261), a selective A(2A) receptor
      antagonist were examined. METHODS: Locomotor stimulation and behavioral
      sensitization of caffeine, DPCPX, and SCH58261 were studied in C57BL/6 male mice
      following acute and chronic administration. Conditioned place preference (CPP)
      paradigm was used to evaluate the drug-seeking potential of these compounds.
      Furthermore, the expression of phospho-Thr75-DARPP-32 in striatal membrane from
      behaviorally sensitized mice was analyzed by Western blot. RESULTS: Caffeine and
      SCH58261 but not DPCPX induced CPP and locomotor sensitization in C57BL/6 mice.
      The locomotor sensitization after chronic treatment was associated with increased
      DARPP-32 phosphorylation at Thr75 in the striatum. CONCLUSION: Caffeine-induced
      reinforcing effect and behavioral sensitization are mediated by antagonism at
      adenosine A(2A) receptor. These effects are associated with phosphorylation of
      DARPP-32 at Thr75 in the striatum.

PMID- 19169673
TI  - Dissociating anxiolytic and sedative effects of GABAAergic drugs using
      temperature and locomotor responses to acute stress.
AB  - RATIONALE: The stress-induced hyperthermia (SIH) model is an anxiety model that
      uses the transient rise in body temperature in response to acute stress.
      Benzodiazepines produce anxiolytic as well as sedative side effects through
      nonselective binding to GABA(A) receptor subunits. The GABA(A) receptor alpha(1)
      subunit is associated with sedation, whereas the GABA(A) receptor alpha(2) and
      alpha(3) subunits are involved in anxiolytic effects. OBJECTIVES: We therefore
      examined the effects of (non)subunit-selective GABA(A) receptor agonists on
      temperature and locomotor responses to novel cage stress. RESULTS: Using
      telemetric monitoring of temperature and locomotor activity, we found that
      nonsubunit-selective GABA(A) receptor agonist diazepam as well as the alpha(3)
      subunit-selective receptor agonist TP003 dose-dependently attenuated SIH and
      locomotor responses. Administration of GABA(A) receptor alpha(1)-selective
      agonist zolpidem resulted in profound hypothermia and locomotor sedation. The
      GABA(A) receptor alpha(1)-selective antagonist betaCCt antagonized the
      hypothermia, but did not reverse the SIH response attenuation caused by diazepam
      and zolpidem. These results suggest an important regulating role for the alpha(1)
      subunit in thermoregulation and sedation. Ligands of extrasynaptic GABA(A)
      receptors such as alcohol and nonbenzodiazepine THIP attenuated the SIH response
      only at high doses. CONCLUSIONS: The present study confirms a putative role for
      the GABA(A) receptor alpha(1) subunit in hypothermia and sedation and supports a
      role for alpha(2/3) subunit GABA(A) receptor agonists in anxiety processes. In
      conclusion, we show that home cage temperature and locomotor responses to novel
      home cage stress provide an excellent tool to assess both anxiolytic and sedative
      effects of various (subunit-selective) GABA(A)ergic compounds.

PMID- 19169675
TI  - Liquid chromatography under critical conditions: practical applications in the
      analysis of amphiphilic polymers.
AB  - Liquid chromatography under critical conditions (LCCC) allows the separation of
      block copolymers from the corresponding homopolymers as well as the separation of
      homopolymers according to their functionality. At the transition of exclusion and
      adsorption mode, the polymer chain becomes "chromatographically invisible," and
      thus a separation according to other structural units can be achieved. In the
      case of block copolymers this situation can be utilized to detect and determine
      unwanted homopolymers. At critical conditions for the repeat unit, the other
      block may be eluted in the exclusion or the adsorption regime. In the first case,
      the block copolymer is eluted before the homopolymer, and its molar mass can be
      determined as in size-exclusion chromatography. In the second case, it is eluted
      later than the homopolymer, and the separation of the individual oligomers can be
      achieved. Advantages and limitations of different approaches in LCCC are
      discussed.

PMID- 19169674
TI  - A neurocomputational account of catalepsy sensitization induced by D2 receptor
      blockade in rats: context dependency, extinction, and renewal.
AB  - RATIONALE: Repeated haloperidol treatment in rodents results in a day-to-day
      intensification of catalepsy (i.e., sensitization). Prior experiments suggest
      that this sensitization is context-dependent and resistant to extinction
      training. OBJECTIVES: The aim of this study was to provide a neurobiological
      mechanistic explanation for these findings. MATERIALS AND METHODS: We use a
      neurocomputational model of the basal ganglia and simulate two alternative models
      based on the reward prediction error and novelty hypotheses of dopamine function.
      We also conducted a behavioral rat experiment to adjudicate between these models.
      Twenty male Sprague-Dawley rats were challenged with 0.25 mg/kg haloperidol
      across multiple days and were subsequently tested in either a familiar or novel
      context. RESULTS: Simulation results show that catalepsy sensitization, and its
      context dependency, can be explained by "NoGo" learning via simulated D2 receptor
      antagonism in striatopallidal neurons, leading to increasingly slowed response
      latencies. The model further exhibits a non-extinguishable component of catalepsy
      sensitization due to latent NoGo representations that are prevented from being
      expressed, and therefore from being unlearned, during extinction. In the rat
      experiment, context dependency effects were not dependent on the novelty of the
      context, ruling out the novelty model's account of context dependency.
      CONCLUSIONS: Simulations lend insight into potential complex mechanisms leading
      to context-dependent catalepsy sensitization, extinction, and renewal.

PMID- 19169676
TI  - The amplitude of physiological tremor can be voluntarily modulated.
AB  - The objective of this study was to determine whether it was possible to
      voluntarily modulate physiological tremor (PT), i.e., reduce its amplitude. We
      recorded the postural index finger tremor of 30 healthy participants with a laser
      in four conditions: (A) eyes closed, without any attempt to modulate PT
      amplitude, (B) no visual feedback, trying to reduce PT amplitude, (C) visual
      feedback, trying to reduce PT amplitude. For conditions B and C, subjects were
      asked to avoid using muscle contraction as a means to stabilize the finger.
      Finally, (D) subjects were asked to reduce PT amplitude using voluntary muscle
      contraction to stabilize the finger. We used electromyography to monitor the
      extensor digitorum communis and flexor digitorum superficialis. Total amplitude
      of PT did not change significantly between conditions A and B. In condition C, a
      significant decrease of PT amplitude was observed. A significant increase in
      tremor amplitude was observed in D compared with other conditions, confirming
      that co-contraction was not used to modulate the amplitude of PT in other
      conditions. Subsequently, we formed three subgroups based on their ability to
      modulate PT: Most Improved (n = 7), Least Improved (n = 16) and Not Improved (n =
      7). Although oscillations within the low frequency bands increased only in the
      Not Improved group, oscillations within the 8-12 and 16-30 Hz bands either
      remained stable or decreased for all participants, supporting a disassociation
      between mechanical-reflex and central components of PT. Our results show that it
      is possible to voluntarily modulate PT. Therefore, a cortical influence is being
      exerted on tremor.

PMID- 19169677
TI  - Health care providers' requests to Teratogen Information Services on medication
      use during pregnancy and lactation.
AB  - BACKGROUND: Medication use during pregnancy and lactation is prevalent. However,
      current knowledge of the risks and benefits of medication use during pregnancy
      and lactation is incomplete as the best available evidence has been obtained from
      cohort studies of inadvertent exposures and registries. This situation may partly
      explain health care providers' (HCP) risk perceptions and thus the increasing
      number of calls to Teratogen Information Services (TIS). OBJECTIVES: The
      objectives of this study were (1) to identify the medication classes for which
      HCP are seeking counseling from the IMAGe center, a Quebec TIS; (2) to identify
      the medical conditions for which medication classes were used during pregnancy
      and lactation; (3) to identify and quantify predictors of medication information
      requests during pregnancy and lactation. METHODS: A retrospective analysis of
      data was conducted within the population served by the IMAGe center, a TIS based
      at CHU Ste-Justine in Montreal, Quebec, Canada, that serves the French population
      of Canada. To be included, calls had to be received between January 1, 2004 and
      April 30, 2007, and the subject of the call had to be directly associated with
      the exposure, or not, of a pregnant or breastfeeding woman to medication.
      Multivariate generalized estimating equation (GEE) regression models were
      performed to identify the predictors of medication requests. RESULTS: A total of
      11, 076 requests regarding medication exposure during pregnancy, 12 055 requests
      regarding pregnant women before the exposure took place, and 13, 364 requests
      regarding lactation were included for analyses. Pregnant women were most
      frequently exposed to antidepressants (17.3), antibiotics (6.3%), and
      benzodiazepines (5.3%). Prior to drug exposure, the most frequent inquiries by
      HCP were on antibiotics (11.0%), anti-inflammatory drugs (6.0%), and antiemetics
      (5.1%). Inquiries concerning lactating women most frequently requested
      information on the drug classes of antidepressants (10.8%), antibiotics (9.1%),
      and anti-inflammatory drugs (7.8%). Depressive disorders were an indication of
      antidepressant, benzodiazepine and antipsychotic exposures reported to IMAGe.
      Associations were found between medication use and maternal age, previous
      pregnancies, trimester of pregnancy at the time of the call and lifestyle habits.
      CONCLUSIONS: The IMAGe received frequent inquiries on antidepressant, antibiotic,
      and benzodiazepine exposures, with depressive disorders being the most frequently
      declared indication. Predictors of medication requests were identified among
      exposed women during pregnancy, and breastfeeding women. These results emphasize
      the need for effective studies on drug use during pregnancy and lactation and for
      better knowledge transfer programs.

PMID- 19169678
TI  - Smoking in pregnancy and lactation: a review of risks and cessation strategies.
AB  - BACKGROUND: Despite documented evidence of harm to fetus and infant, a
      substantial number of women continue to smoke during pregnancy and lactation.
      OBJECTIVE: To examine the literature regarding smoking during pregnancy and
      breastfeeding to ascertain adverse effects as well as the efficacy of
      interventions to enable women to stop smoking in the perinatal period. STUDY
      DESIGN: A comprehensive literature search was undertaken to identify all
      published studies reporting on smoking in pregnancy and lactation. MEDLINE,
      EMBASE, PUBMED, and Web of Science databases were searched for studies published
      in English from 1966 to 2008 that reported on smoking in pregnancy and
      breastfeeding, with information on adverse effects and on all forms of smoking
      cessation, including behavioral interventions, nicotine replacement therapy, and
      pharmacotherapy such as antidepressants. RESULTS: There is evidence that smoking
      in pregnancy and lactation may cause many adverse affects in the perinatal
      period, childhood, and up to adulthood. These adverse effects include
      infertility, ectopic pregnancy, spontaneous abortion, placenta insufficiency, low
      birth weight, fetal growth restriction, preterm delivery, orofacial clefts, SIDS,
      craniosynostosis, clubfoot, childhood respiratory disease, attention deficit
      disorder, and some childhood cancers. A number of strategies have been developed
      to assist pregnant women in quitting smoking, including both behavioral
      interventions and pharmacological therapies, such as nicotine replacement and
      antidepressant therapy. CONCLUSIONS: Behavioral interventions report only modest
      success rates. Nicotine replacement therapy and antidepressants appear to be safe
      to use in pregnancy, but do not achieve a substantially higher success rate for
      quitting.

PMID- 19169679
TI  - Transarticular spread of Ewing sarcoma mimicking septic arthritis.
AB  - Transarticular spread of tumor is rare; it has only been reported in the
      sacroiliac joint, intervertebral disk spaces, and facet joints. The anatomic and
      kinetic characteristics of the sacroiliac joint, as well as the changes the joint
      undergoes during a lifetime, make it particularly vulnerable to transarticular
      tumor invasion. Although extremely rare, Ewing sarcoma can extend through the
      sacroiliac joint and be virtually indistinguishable radiologically from septic
      arthritis. Furthermore, the clinical presentation of a child with Ewing sarcoma
      can be similar to that of a child with osteomyelitis. Laboratory values are quite
      nonspecific and are not always helpful in differentiating between the entities.
      Therefore, the possibility of sacroiliac joint transarticular Ewing sarcoma
      should be considered in a child presenting with hip pain, despite clinical,
      radiological and laboratory findings suggesting an infectious process.

PMID- 19169680
TI  - Isolation of a novel high erythritol-producing Pseudozyma tsukubaensis and scale
      up of erythritol fermentation to industrial level.
AB  - This study isolated a novel erythritol-producing yeast strain, which is capable
      of growth at high osmolarity. Characteristics of the strain include asexual
      reproduction by multilateral budding, absence of extracellular starch-like
      compounds, and a negative Diazonium blue B color reaction. Phylogenetic analysis
      based on the 26S rDNA sequence and physiological analysis indicated that the
      strain belongs to the species Pseudozyma tsukubaensis and has been named P.
      tsukubaensis KN75. When P. tsukubaensis KN75 was cultured aerobically in a fed
      batch culture with glucose as a carbon source, it produced 245 g/L of erythritol,
      corresponding to 2.86 g/L/h productivity and 61% yield, the highest erythritol
      yield ever reported by an erythritol-producing microorganism. Erythritol
      production was scaled up from a laboratory scale (7 L fermenter) to pilot (300 L)
      and plant (50,000 L) scales using the dissolved oxygen as a scale-up parameter.
      Erythritol production at the pilot and plant scales was similar to that at the
      laboratory scale, indicating that the production of erythritol by P. tsukubaensis
      KN75 holds commercial potential.

PMID- 19169682
TI  - Memory and cellular immunity induced by a DNA vaccine encoding self antigen TPD52
      administered with soluble GM-CSF.
AB  - Tumor protein D52 (TPD52) is involved in cellular transformation, proliferation
      and metastasis. TPD52 over expression has been demonstrated in several cancers
      including prostate, breast, and ovarian carcinomas. Murine TPD52 (mD52) has been
      shown to induce anchorage independent growth in vitro and metastasis in vivo, and
      mirrors the function and normal tissue expression patterns of the human
      orthologue of TPD52. We believe TPD52 represents a self, non-mutated tumor
      associated antigen (TAA) important for maintaining a transformed and metastatic
      cellular phenotype. The transgenic adeno-carcinoma of the mouse prostate (TRAMP)
      model was employed to study mD52 as a vaccine antigen. Naive mice were immunized
      with either recombinant mD52 protein or plasmid DNA encoding the full-length cDNA
      of mD52. Following immunization, mice were challenged with a subcutaneous,
      tumorigenic dose of mD52 positive, autochthonous TRAMP-C1 tumor cells. Sixty
      percent of mice were tumor free 85 days post challenge with TRAMP-C1 when
      immunized with mD52 as a DNA-based vaccine admixed with soluble granulocyte
      macrophage colony stimulating factor (GM-CSF). Survivors of the initial tumor
      challenge rejected a second tumor challenge given in the opposite flank
      approximately 150 days after the first challenge, and remained tumor free for
      more than an additional 100 days. The T cell cytokine secretion patterns from
      tumor challenge survivors indicated that a T(H)1-type cellular immune response
      was involved in tumor protection. These data suggest that mD52 vaccination
      induced a memory, cellular immune response that resulted in protection from
      murine prostate tumors that naturally over express mD52 protein.

PMID- 19169681
TI  - Posttherapeutic (131)I SPECT-CT offers high diagnostic accuracy when the findings
      on conventional planar imaging are inconclusive and allows a tailored patient
      treatment regimen.
AB  - PURPOSE: The purpose of this prospective study was to determine the diagnostic
      impact and influence on patient treatment of posttherapeutic (131)I SPECT-CT when
      the findings on planar posttherapeutic whole-body scintigraphy (ptWBS) were
      inconclusive. MATERIALS AND METHODS: A total of 53 SPECT-CT scans were performed
      in 41 patients with thyroid cancer after high-dose (131)I therapy (2.944 to 7.526
      GBq (131)I) because of diagnostic uncertainty on ptWBS. Physiological uptake in
      the salivary glands, gastric mucosa, gut, nasal mucosa, urinary tract and liver
      were considered to be normal. Any other foci of increased (131)I uptake, except
      iodine uptake clearly located in the thyroid bed, were considered to be abnormal.
      The data were evaluated on a lesion and a patient basis. RESULTS: Regarding neck
      lesions, SPECT-CT provided a diagnostic impact in 26/90 lesions (28.9%) and
      confirmed the diagnosis in 64/90 lesions (71.1%). On a patient basis, SPECT-CT
      changed N status in 12/33 patients (36.4%), provided a diagnostic impact in 21/33
      patients (63.6%) and led to a treatment change in 8/33 patients (24.2%).
      Regarding lesions distant from the neck, SPECT-CT confirmed the diagnosis in
      62/71 lesions (87.3%) and had a diagnostic impact in 9/71 lesions (12.7%). On a
      patient basis, SPECT-CT changed M status in 4/19 patients (21.1%), had a
      diagnostic impact in 14/19 patients (73.7%) and led to a treatment change in 2/19
      patients (10.5%). Considering all patients, SPECT-CT led to a treatment change in
      10/41 patients (24.4%). CONCLUSION: Integrated SPECT-CT is a useful tool,
      especially in cases of diagnostic uncertainty and helps to individualize patient
      management.

PMID- 19169683
TI  - A phase II study of lapatinib in patients with advanced biliary tree and
      hepatocellular cancer.
AB  - PURPOSE: To evaluate the response to lapatinib, an inhibitor of epidermal growth
      factor receptors 1 and 2, in patients with advanced bilary tree cancer (BTC) and
      hepatocellular cancer (HCC). METHODS: Lapatinib was dosed at 1,500 mg/day orally
      continuously. RESULTS: Fifty-seven patients were accrued (BTC 17, HCC 40).
      Therapy was well tolerated. The response in BTC was 0% and in HCC was 5%. The
      progression free survival (PFS) for BTC and HCC patients was 1.8 (95% CI: 1.7
      5.2) months and 2.3 (95% CI: 1.7-5.6) months. The median survival for BTC and HCC
      patients was 5.2 (95% CI 3.3-infinity) months and 6.2 (95% CI: 5.1-infinity)
      months. EGFR genotyping indicated HCC patients with <20 repeats have the lowest
      PFS. The occurrence of any skin rash significantly prolonged PFS and survival.
      CONCLUSIONS: Lapatinib was well-tolerated. There was evidence of activity in HCC,
      but therapy with lapatinib did not meet the predefined efficacy rate.

PMID- 19169684
TI  - Fotemustine as second-line treatment for recurrent or progressive glioblastoma
      after concomitant and/or adjuvant temozolomide: a phase II trial of Gruppo
      Italiano Cooperativo di Neuro-Oncologia (GICNO).
AB  - BACKGROUND: Standardized salvage treatment has not yet proved effective in
      glioblastoma multiforme (GBM) patients who receive prior standard radiotherapy
      plus concomitant and adjuvant temozolomide. METHODS: Patients with progressive
      GBM after radiotherapy plus concomitant and/or adjuvant temozolomide received
      three-weekly doses (100-75 mg m(2)) of fotemustine followed, after a 5-week rest,
      by fotemustine (100 mg m(2)) every 3 weeks for < or =1 year. RESULTS: Forty-three
      patients (29 M, 14 F; median age 51 years, range 34-68; median KPS 90) were
      enrolled. Progression-free survival at 6 months (PFS-6) was 20.9% (95% CI: 9
      33%); three patients (7.1%) had partial response (PR); 15 (34.9%), disease
      stabilization (SD). The median survival was 6 months (95% CI: 5-7). MGMT promoter
      status was methylated in 8 (18.6%) and unmethylated in 26 (60.5%) and not
      assessable in 9 (20.9%) patients, respectively. Disease control was 75% versus
      34.6% in methylated and unmethylated MGMT patients (P = 0.044); no significant
      difference was found between groups for PFS-6 and survival. Grade 3 and 4
      thrombocytopenia and neutropenia were observed in 20.9 and 16.3% of patients,
      during the induction phase, and in 0 and 9.5% patients during the maintenance
      phase, respectively. CONCLUSIONS: The findings of the present trial, that
      evaluate fotemustine in a homogeneous population, may represent a new benchmark
      for nitrosourea activity. Moreover, this is the first study to evaluate
      correlation between MGMT promoter status and outcome of fotemustine for relapsing
      GBM previously treated with radiotherapy and temozolomide.

PMID- 19169685
TI  - SNS-032 is a potent and selective CDK 2, 7 and 9 inhibitor that drives target
      modulation in patient samples.
AB  - PURPOSE: SNS-032 (formerly BMS-387032) is a potent, selective inhibitor of cyclin
      dependent kinases (CDK) 2, 7 and 9, currently in phase 1 clinical trial for
      chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We used the MM cell
      line RPMI-8226 to evaluate the relationship between duration of SNS-032 exposure,
      target modulation of CDKs 2, 7 and 9, and induction of apoptosis. We also
      assessed target modulation in patient peripheral blood mononuclear cells (PBMCs)
      from phase 1 solid tumor patients treated with SNS-032. METHODS: Proliferation
      and colony forming assays were used to evaluate cytotoxicity, Western blot
      analyses to evaluate target modulation, FACS analysis to assess cell cycle
      distribution, RT-PCR to evaluate transcriptional inhibition. RESULTS: SNS-032
      blocks the cell cycle via inhibition of CDKs 2 and 7, and transcription via
      inhibition of CDKs 7 and 9. Treatment of RPMI-8226 MM cells at 300 nM (IC(90))
      for 6 h was sufficient for commitment to apoptosis. This correlated with
      inhibition of CDKs 2, 7 and 9, as reflected in substrate signaling molecules. SNS
      032 activity was unaffected by human serum. Target modulation was observed in
      PBMC from treated patients. CONCLUSIONS: These results demonstrate SNS-032 target
      modulation of CDKs 2, 7 and 9, and establish 6 h exposure as sufficient to commit
      RPMI-8226 MM cells to apoptosis. Combined with the demonstration of target
      modulation in PBMC from phase 1 solid tumor patients treated with SNS-032, these
      data support the ongoing clinical study of SNS-032 in MM and CLL.

PMID- 19169686
TI  - Simvastatin plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first
      line chemotherapy in metastatic colorectal patients: a multicenter phase II
      study.
AB  - BACKGROUND: Simvastatin has demonstrated anti-tumor activity in preclinical
      studies via tumor cell senescence, anti-angiogenesis, and apoptosis. This phase
      II trial evaluated the efficacy and toxicity profile of conventional FOLFIRI
      chemotherapy plus simvastatin in metastatic colorectal cancer patients. METHODS:
      Patients received irinotecan 180 mg/m(2) as a 90-min infusion followed by
      leucovorin 200 mg/m(2) in a 2-h infusion, and then 5-FU 400 mg/m(2) bolus
      injection followed by 2,400 mg/m(2) as a 46-h continuous infusion. Treatment
      cycles were repeated every 2 weeks until documented disease progression,
      unacceptable toxicity, or patient's refusal. Simvastatin 40 mg tablet was given
      once daily per oral everyday during the period of chemotherapy without a rest.
      RESULTS: From October 2005 to June 2006, 49 patients were enrolled. The overall
      response rate (ORR) was 46.9% (95% CI, 31.0-58.8) by intent-to-treat analysis and
      45.8% (95% CI, 33.3-62.8) by per-protocol analysis. There were one complete
      response (CR) and 22 partial responses (PRs). Both CR and PRs were confirmed at
      least 4 weeks later. The disease-control rate was 83.7% (95% CI, 73.4-94.0). The
      median follow-up duration was 25.6 months (range, 20.9-28.8 months). The median
      survival of all patients was 21.8 months (95% CI, 14.4, 29.2). The median TTP was
      9.9 months (95% CI, 6.4, 13.3). No patients experienced additional adverse effect
      that was definitely caused by simvastatin drug therapy in this trial. CONCLUSION:
      The combination of simvastatin plus FOLFIRI was a feasible regimen with promising
      antitumor activity.

PMID- 19169687
TI  - A phase I escalating single-dose and weekly fixed-dose study of cetuximab
      pharmacokinetics in Japanese patients with solid tumors.
AB  - PURPOSE: Cetuximab is a therapeutic immunoglobulin G1 monoclonal antibody that
      recognizes the epidermal growth factor receptor (EGFR). This phase I dose
      escalation study was designed to assess the safety and pharmacokinetics (PK) of
      cetuximab in Japanese patients with EGFR-expressing, advanced, solid tumors and
      also to look for evidence of antitumor efficacy. PATIENTS AND METHODS: Thirty
      patients were enrolled in the study; 29 with colorectal adenocarcinomas and one
      with an adenocarcinoma of the lung. Patients received an initial/weekly infusion
      of cetuximab at dose levels of 100/100 (dose level 1), 250/250 (dose level 2),
      400/250 (dose level 3), 500/250 (dose level 4) or 400/250 (dose level 5) mg/m(2),
      for 7 or more weeks, with an interval between the initial and second infusion of
      1 (dose level 5 representing the standard regimen) or 2 weeks (dose levels 1-4 of
      the non-standard regimens). RESULTS: No dose-limiting toxicities (DLTs) were
      observed during the evaluation period. All patients had at least one adverse
      event (AE). The most common cetuximab-related AEs were skin toxicity (93% of
      patients), including acneiform dermatitis (83% of patients). Two patients
      experienced cetuximab-related grade 3 AEs of skin toxicity and diarrhea after DLT
      evaluation. C (max) and AUC(0-infinity) after the initial infusion showed dose
      proportional increases. Mean total body clearance (CL) values decreased with dose
      at the lower dose levels. At doses of >or=400 mg/m(2), CL values appeared to
      level off. Mean trough concentrations for dose level 5 were constant from week 4
      (day 29) onward. Two patients (8%) achieved partial response (at 100/100
      mg/m(2)). The overall disease control rate (partial response + stable disease)
      was 58%. CONCLUSION: The current study demonstrated that cetuximab PK and safety
      profiles are similar between Japanese and non-Japanese patient populations. It
      would appear that the standard dose of an initial 2-h infusion of 400 mg/m(2)
      followed thereafter by weekly 1-h infusions of 250 mg/m(2) for non-Japanese
      patients is feasible for future clinical studies in Japanese patients.

PMID- 19169688
TI  - Successful twin pregnancy while on cyclophosphamide therapy in a patient with
      lupus nephritis.

PMID- 19169689
TI  - Bronchial morphometry in smokers: comparison with healthy subjects by using 3D
      CT.
AB  - The assessment of airway dimensions in patients with airway disease by using
      computed tomography (CT) has been limited by the obliquity of bronchi, the
      ability to identify the bronchial generation, and the limited number of bronchial
      measurements. The aims of the present study were (i) to analyze cross-sectional
      bronchial dimensions after automatic orthogonal reconstruction of all visible
      bronchi on CT images, and (ii) to compare bronchial morphometry between smokers
      and nonsmokers. CT and pulmonary function tests were performed in 18 males
      separated into two groups: 9 nonsmokers and 9 smokers. Bronchial wall area (WA)
      and lumen area (LA) were assessed using dedicated 3D software able to provide
      accurate cross-sectional measurements of all visible bronchi on CT. WA/LA and
      WA/(WA+LA) ratios were computed and all parameters were compared between both
      groups. Smokers demonstrated greater WA, smaller LA, and consequently greater
      LA/WA and LA/(WA+LA) ratios than nonsmokers. These differences occurred downward
      starting at the fourth bronchial generation. 3D quantitative CT method is able to
      demonstrate significant changes in bronchial morphometry related to tobacco
      consumption.

PMID- 19169691
TI  - Seasonal changes in lipid composition and glycogen storage associated with freeze
      tolerance of the earthworm, Dendrobaena octaedra.
AB  - The earthworm, Dendrobaena octaedra, is a common species in the uppermost soil
      and humus layers of coniferous forests and tundra in temperate and subarctic
      regions. The species is freeze-tolerant and may survive several months in a
      frozen state. Upon freezing, glycogen reserves are rapidly converted to glucose
      serving as a cryoprotectant and fuel for metabolism. In the present study we
      investigated the induction of freeze-tolerance under field conditions, and sought
      to find relationships between temperature, glycogen and fat reserves, membrane
      phospholipid composition and the degree of freeze-tolerance. Freeze-tolerance was
      induced when worms had experienced temperatures below 5 degrees C for 2 weeks or
      more. Freeze-tolerance was linked to the magnitude of glycogen reserves, which
      also fluctuated with field temperatures being highest in autumn and winter. On
      the other hand fat reserves seemed not to be linked with freeze-tolerance at all.
      However, high glycogen alone did not confer freeze-tolerance; alterations in the
      membrane phospholipid fatty acid composition (PLFA) were also necessary in order
      to secure freeze-tolerance. The changes in PLFA composition were generally
      similar to changes occurring in other ectothermic animals during winter
      acclimation with an increased degree of unsaturation of the PLFAs.

PMID- 19169690
TI  - Long-term retention of gadolinium in the skin of rodents following the
      administration of gadolinium-based contrast agents.
AB  - Several publications suggest a potential association between the administration
      of Gadolinium-based contrast agents (GBCAs) and the onset of a rare but serious
      disease, Nephrogenic Systemic Fibrosis (NSF). The aim of this study was to
      determine the elimination time-course of Gadolinium (Gd) from skin tissue after
      application of GBCAs in rats. Seven different marketed GBCAs were injected on
      five consecutive days at a dose of 2.5 mmol/kg bodyweight into the tail vein of
      Han-Wistar rats and the Gd concentrations were determined by Inductively Coupled
      Plasma Mass Spectrometry (ICP-MS) in skin biopsies taken at various time-points
      up to a year after the last injection. Most of the administered Gd was eliminated
      from the skin within a time-period of about 2 months. However, the repeated
      administration of linear GBCAs resulted in long-term retention of a small portion
      of the administered Gd in the skin tissue of rats, with substantially higher
      values observed in animals treated with non-ionic linear agents than in those
      that received ionic linear GBCAs. Following treatment with macrocyclic GBCAs, Gd
      values in the skin were in the same range as observed in the controls from day 24
      post-injection onwards. In summary, we observed a correlation between the complex
      stability of GBCAs and the amount of residual Gd in the skin up to a year after
      application of GBCAs.

PMID- 19169692
TI  - Rapid correction of metabolic alkalosis in hypertrophic pyloric stenosis with
      intravenous cimetidine: preliminary results.
AB  - PURPOSE: Pyloromyotomy has been the treatment of choice for hypertrophic pyloric
      stenosis (HPS) for the past century. In most HPS cases, there is mild metabolic
      alkalosis, which requires intravenous fluid resuscitation with 5% dextrose/normal
      saline for 1-2 days. However, in some cases, due to a delay in diagnosis,
      alkalosis becomes severe and a much longer resuscitation period (5-10 days) is
      required to normalize serum pH. Metabolic alkalosis of HPS results from excessive
      vomiting of hydrochloric acid; and therefore if its production is reduced, serum
      pH can be normalized faster. In this study, the use of intravenous cimetidine
      (CM) in a small number of infants with HPS is presented. METHODS: Over a 28-month
      period, 32 HPS cases, including a sub-group of 17 infants (aged 7-9 weeks) with
      arterial pH >7.60, were admitted to a tertiary referral unit. Four infants in
      this sub-group were treated with standard resuscitation fluids for 4 days prior
      to intravenous CM, while 12 infants received CM immediately. Intravenous CM (10
      mg/kg) was given at twice daily until arterial pH was less than 7.50. In one
      case, intravenous omeprazole at 0.1 mg/kg was given instead of CM. RESULTS: In
      all 17 cases, CM treatment or omeprazole therapy (for 12-48 h) reduced pH to less
      than 7.50, thus allowing for Ramstedt pyloromyotomy the same day. These patients
      were allowed oral feeding on the following day and were discharged at 1-3 post
      operative days. No complications due to CM (or omperazole) treatment were
      observed. CONCLUSION: Intravenous CM administration can rapidly normalize severe
      metabolic alkalosis in HPS patients. As a result, pyloromyotomy can be performed
      sooner reducing both hospital stay and costs.

PMID- 19169693
TI  - Is simple mucosal resection really possible? Considerations about histological
      findings after stapled hemorrhoidopexy.
AB  - INTRODUCTION: The common removal of smooth muscle during stapled hemorrhoidectomy
      had raised concerns about its effects on postoperative anorectal function. The
      purpose of the study is to confirm the high frequency of the involvement of
      smooth muscle fibers in stapled hemorrhoidectomy and to determine its association
      with postoperative findings. METHODS: This retrospective study evaluated 241
      cases of stapled hemorrhoidopexy treated from 2003 to 2006. Data include the most
      common postoperative complications such as bleeding, anal pain, and recurrence.
      Histological doughnuts were examined, and the presence of muscle fibers was
      evaluated. RESULTS: Early complications occurred in 27/241 patients (11.2%)
      including bleeding (14), anal pain (eight), incontinence (two), abscess (two),
      hematoma (one). Recurrence was observed in 11 cases (4.5%). Muscularis propria
      fibers were identified in 217 of 241 (90%) pathologic specimens. Five
      complications occurred in the group in which muscle fibers were not identified
      (4/24). The frequency of complications in the group with and without smooth
      muscle tissue in the resected specimens was 9.6% and 25%, respectively.
      CONCLUSIONS: The presence of muscle fibers is not an occasional finding in the
      histological specimens, even if the presence of smooth muscle does not seems to
      influence the outcome of stapled hemorrhoidopexy. The idea of a simple mucosal
      resection needs to be revised.

PMID- 19169694
TI  - Boutonniere deformity of the second toe after planter dislocation of proximal
      interphalangeal joint: a case report.
AB  - The boutonniere deformity is a well-known deformity in the fingers, however, its
      appearance on a lessor toe is extremely rare. In the present case, the deformity
      resulted from a rupture of the central slip of the extensor tendon and the shift
      of the lateral bands to the planter side after reduction of a traumatic planter
      dislocation of the PIP joint of the second toe. Surgical repair of the extensor
      mechanism brought good results.

PMID- 19169695
TI  - Minimally invasive plate osteosynthesis of subtrochanteric femur fractures with a
      locking plate: a prospective series of 20 fractures.
AB  - BACKGROUND: Intramedullary nailing is a mainstay in the treatment of
      subtrochanteric femoral fractures. But nailing is often unsuitable for difficult
      fracture patterns with comminution or when the medullary canal is narrow. The
      purpose of this study was to clarify the efficacy of minimally invasive plate
      osteosynthesis (MIPO) with locking compression plate in the treatment of
      subtrochanteric fractures. METHODS: Twenty patients with subtrochanteric
      fractures (mean age 49.6 years) were prospectively treated using the MIPO
      technique using a locking plate. Indications of procedure were fractures with the
      greater trochanter or medial comminution, and multiple injured patients with a
      narrow femoral canal. According to the AO/OTA classification, there were three of
      type A, eight of type B, and nine of type C. RESULTS: All healed without bone
      graft, at an average of 20.1 weeks (range 16-32). With the exception of two
      patients with minor internal rotation deformity and one patient with 1 cm of
      shortening, most achieved acceptable alignment. All patients were able to walk
      with no or only a slight limp, and median Merle d'Aubigne score was 17.3 (15-18).
      Four patients complained of a slight pain in the trochanteric area due to plate
      prominence. The MIPO technique with a locking plate provides an alternative
      method for fixing subtrochanteric femur fractures, when IM nailing is
      inappropriate. This technique provides stable fixation, with a high union rate
      and a minimal complication rate.

PMID- 19169696
TI  - Removal of broken solid femoral nail: a modified bent tip guide wire technique.
AB  - A broken solid femoral nail can be challenging to remove. We describe a modified
      bent tip guide wire technique for extraction of a broken solid retrograde femoral
      nail from the proximal femur. The broken nail was removed successfully through
      the original retrograde entry point to allow for an exchange femoral nailing in a
      patient with a hypertrophic non-union. This novel technique avoids any additional
      exposure other than that required to remove and insert the nail.

PMID- 19169698
TI  - Harlequin icthyosis: report of one case.
AB  - Harlequin icthyosis is a rare extremely severe autosomal recessive dermatosis.
      The appearance of newborn can be shocking to parents and health care providers.
      Prenatal diagnosis is possible only with great suspicion and can often be missed.
      To our knowledge only 100 cases have been reported so far, we report one case of
      harlequin icthyosis.

PMID- 19169697
TI  - Status of essential trace metals in biological samples of diabetic mother and
      their neonates.
AB  - OBJECTIVE: There is accumulating facts that the metabolism of essential trace
      elements is altered in diabetic patients. The aim of present study was to compare
      the status of essential trace elements, chromium (Cr), manganese (Mn), and zinc
      (Zn) in biological samples (whole blood, urine and scalp hair) of insulin
      dependent diabetic mothers (age ranged 30-40) and their newly born infants (n =
      76). An age matched 68 non-diabetic mothers and their infants, residing in the
      same locality, were selected as referents. For a comparative study, the
      biological samples of non-diabetic and diabetic pregnant and non pregnant of same
      age group and socio-economics status were also analysed. METHODOLOGY: The
      biological samples (scalp hair, blood and urine) were collected from study and
      referent groups. The Cr, Mn and Zn concentrations in all three biological samples
      were determined by a flame/electrothermal atomic absorption spectrometer, prior
      to microwave assisted acid digestion. The validity and accuracy of the
      methodology was checked by certified reference materials (CRMs) and using
      conventional wet acid digestion method on same CRMs. RESULTS: The mean values of
      Cr, Mn and Zn in scalp hair and blood samples of diabetic mothers and their
      infants were significantly lower as compared to the referent mothers-infants
      pairs (p < 0.01), while urinary excretion of all these elements were high in
      diabetic mother-infant pair samples. CONCLUSION: The deficiencies of essential
      trace elements, Cr, Mn and Zn in biological samples of diabetic women, may play
      role in the pathogenesis of diabetes mellitus and impacts on their neonates.

PMID- 19169699
TI  - Metastasized hemangiopericytoma of the breast: a rare case.
AB  - Sarcoma of the mammary glands is extremely rare. Liposarcoma, leiomyosarcoma,
      rhabdomyosarcoma, as well as hemangiopericytoma, are part of the soft tissue
      sarcoma group. Little is known about the progress, prognosis and dissemination of
      this infrequent tumor entity. We present the case of a woman, who received
      primary diagnosis of a malignant hemangiopericytoma of the left breast. She
      underwent a mastectomy with an axillary lymph node sampling (stage pT3 pN0 cM0),
      as adjuvant therapy was not mandatory. Eight months after diagnosis, the patient
      presented with lumbar back pain, gluteal pain and right accentuated adynamia in
      both legs because of a disseminated osseous metastasis. Diagnostic investigation
      presented a cerebral, pulmonary, cutaneous, hepatic and pleural metastatic
      disease. Two months after initiation of chemotherapy the patient died. Diagnostic
      criteria and treatment principles in the metastatic situation are presented in
      addition to the literature to give a review about this rare malignancy.

PMID- 19169700
TI  - Appendiceal endometriosis presenting as perforated appendicitis: report of a case
      and review of the literature.
AB  - While endometriosis is a common disorder in women of reproductive age,
      appendiceal endometriosis accounts for less than 1% of all pelvic endometriotic
      lesions. Involvement at this site may present as acute appendicitis and be
      diagnosed only upon postoperative histopathologic examination. We report such an
      occurrence of appendiceal endometriosis in a 40-year-old woman who presented with
      acute perforated appendicitis.

PMID- 19169701
TI  - The Cosmic Silence experiment: on the putative adaptive role of environmental
      ionizing radiation.
AB  - Previously we reported that yeast and Chinese hamster V79 cells cultured under
      reduced levels of background environmental ionizing radiation show enhanced
      susceptibility to damage caused by acute doses of genotoxic agents. Reduction of
      environmental radiation dose rate was achieved by setting up an underground
      laboratory at Laboratori Nazionali del Gran Sasso, central Italy. We now report
      on the extension of our studies to a human cell line. Human lymphoblastoid TK6
      cells were maintained under identical in vitro culture conditions for six
      continuous months, at different environmental ionizing radiation levels. Compared
      to "reference" environmental radiation conditions, we found that cells cultured
      in the underground laboratories were more sensitive to acute exposures to
      radiation, as measured both at the level of DNA damage and oxidative metabolism.
      Our results are compatible with the hypothesis that ultra-low dose rate ionizing
      radiation, i.e. environmental radiation, may act as a conditioning agent in the
      radiation-induced adaptive response.

PMID- 19169702
TI  - Adipophilin distribution and colocalization with lipid droplets in skeletal
      muscle.
AB  - Intramyocellular lipids (IMCL) are stored as discrete lipid droplets which are
      associated with a number of proteins. The lipid droplet-associated protein
      adipophilin (the human orthologue of adipose differentiation-related protein) is
      ubiquitously expressed and is one of the predominant lipid droplet-proteins in
      skeletal muscle. The aim of this study was to investigate the subcellular
      distribution of adipophilin in human muscle fibres and to measure the
      colocalization of adipophilin with IMCL. Muscle biopsies from six lean male
      cyclists (BMI 23.4 +/- 0.4, aged 31 +/- 2 years, W (max) 346 +/- 8) were stained
      for myosin heavy chain type 1, IMCL, adipophilin and mitochondria using
      immunofluorescence and viewed with widefield and confocal fluorescence
      microscopy. The present study shows that like IMCL, the adipophilin content is
      ~twofold greater in type I skeletal muscle fibres and is situated in the areas
      between the mitochondrial network. Colocalization analysis demonstrated that 61
      +/- 2% of IMCL contain adipophilin. Although the majority of adipophilin is
      contained within IMCL, 36 +/- 4% of adipophilin is not associated with IMCL. In
      conclusion, this study indicates that the IMCL pool is heterogeneous, as the
      majority but not all IMCL contain adipophilin.

PMID- 19169704
TI  - Overlapping expression patterns and differential transcript levels of phosphate
      transporter genes in arbuscular mycorrhizal, Pi-fertilised and phytohormone
      treated Medicago truncatula roots.
AB  - A microarray carrying 5,648 probes of Medicago truncatula root-expressed genes
      was screened in order to identify those that are specifically regulated by the
      arbuscular mycorrhizal (AM) fungus Gigaspora rosea, by P(i) fertilisation or by
      the phytohormones abscisic acid and jasmonic acid. Amongst the identified genes,
      21% showed a common induction and 31% a common repression between roots
      fertilised with P(i) or inoculated with the AM fungus G. rosea, while there was
      no obvious overlap in the expression patterns between mycorrhizal and
      phytohormone-treated roots. Expression patterns were further studied by comparing
      the results with published data obtained from roots colonised by the AM fungi
      Glomus mosseae and Glomus intraradices, but only very few genes were identified
      as being commonly regulated by all three AM fungi. Analysis of P(i)
      concentrations in plants colonised by either of the three AM fungi revealed that
      this could be due to the higher P(i) levels in plants inoculated by G. rosea
      compared with the other two fungi, explaining that numerous genes are commonly
      regulated by the interaction with G. rosea and by phosphate. Differential gene
      expression in roots inoculated with the three AM fungi was further studied by
      expression analyses of six genes from the phosphate transporter gene family in M.
      truncatula. While MtPT4 was induced by all three fungi, the other five genes
      showed different degrees of repression mirroring the functional differences in
      phosphate nutrition by G. rosea, G. mosseae and G. intraradices.

PMID- 19169703
TI  - Preoperative cholangitis independently increases in-hospital mortality after
      combined major hepatic and bile duct resection for hilar cholangiocarcinoma.
AB  - PURPOSE: This study evaluated the impact of ductal bile bacteria (bactibilia or
      cholangitis) on the development of surgical site infection (SSI) or in-hospital
      mortality after resection for hilar cholangiocarcinoma. MATERIALS AND METHODS: A
      retrospective analysis was conducted on 81 patients who underwent a combined
      major hepatic (hemihepatectomy or more extensive hepatectomy) and bile duct
      resection for hilar cholangiocarcinoma. Ductal bile was submitted for bacterial
      culture before or during the operation. RESULTS: The incidence of SSI was higher
      in patients with preoperative bactibilia (83%) than in patients without (52%; P =
      0.008). Preoperative bactibilia was an independent variable associated with SSI
      (relative risk 9.003; P = 0.002). The incidence of in-hospital mortality was
      higher in patients with preoperative cholangitis (33%) than in patients without
      (6%; P = 0.009). Preoperative cholangitis was the only independent variable
      associated with in-hospital mortality (relative risk 9.115; P = 0.006).
      CONCLUSIONS: Preoperative cholangitis independently increases in-hospital
      mortality after combined major hepatic and bile duct resection for hilar
      cholangiocarcinoma, whereas preoperative bactibilia independently increases SSI.

PMID- 19169705
TI  - The intergenic region of Arabidopsis thaliana cab1 and cab2 divergent genes
      functions as a bidirectional promoter.
AB  - Genetic engineering plays a unique role in fundamental plant biology studies and
      in improving crop traits. These efforts often necessitate introduction and
      expression of multiple genes using promoters from a very limited repertoire.
      Current common practice of expressing multiple genes is the repeated use of the
      same or similar promoters. This practice causes more frequent transgene silencing
      due to a high degree of sequence homology and a greater chance of rearrangement
      among repeatedly used promoter sequences. Therefore, availability and use of
      natural bidirectional promoters to minimize gene silencing and achieve desirable
      expression pattern of transgenes is a critical issue in the field of plant
      genetic engineering. Here we describe the use of a single natural bidirectional
      promoter to drive the expression of two reporter genes in onion epidermal cells
      and in transgenic tobacco plants. We show that (1) the promoter drives the
      simultaneous expression of GUS and GFP reporter genes after transient expression
      and stable transformation, (2) the transcription is equally strong in both
      directions, (3) immediate upstream regions in each direction control
      transcription independently from each other, and (4) the reporter genes are
      expressed in leaves and stems but not in roots, as expected from the fact that
      the endogenous promoter controls the expression of two photosynthetic genes in
      Arabidopsis. Hence, use of bidirectional promoters in heterologous background
      provides a means to express multiple genes in transgenic plants and aids genetic
      engineering-based crop improvement.

PMID- 19169706
TI  - Comprehensive immunohistochemical analysis of Her-2/neu oncoprotein
      overexpression in breast cancer: HercepTest (Dako) for manual testing and Her
      2/neuTest 4B5 (Ventana) for Ventana BenchMark automatic staining system with
      correlation to results of fluorescence in situ hybridization (FISH).
AB  - Overexpression of Her-2/neu-oncoprotein is used as marker for Herceptin therapy.
      To investigate the sensitivity and specificity of automatic immunohistochemistry
      (Benchmark, Ventana), we compared the results to the manual testing (Dako) in 130
      breast carcinomas and validated the results by fluorescence in situ hybridization
      (FISH). Manual and automatic immunohistochemistry of Her-2/neu-oncoprotein using
      two different antibodies (HercepTest, Her-2/neuTest 4B5) was analyzed. FISH was
      performed in all cases with uncertain or strong overexpression in either
      immunohistochemical stainings or with different immunohistochemical results. Same
      immunohistochemical results were seen in 73.8%. Two cases with overexpression,
      detected with Her-2/neuTest 4B5 and confirmed by FISH, showed no overexpression
      using HercepTest. From 21 cases with 2+ by Her-2/neuTest 4B5, 15 cases had no
      gene amplification (two of them with 3+ HercepTest); three cases showed a gene
      amplification (one of them with failing overexpression by HercepTest); two other
      cases were polysomic; one could not be analyzed. Ventana immunohistochemistry
      seems to be of same reliability like Dako with a little better concordance to
      FISH in our study.

PMID- 19169707
TI  - CD3+ T large granular lymphocyte leukaemia in a HIV+, HCV+, HBV+ patient.

PMID- 19169708
TI  - Mannose-binding lectin polymorphisms and recurrent respiratory tract infection in
      Chinese children.
AB  - In order to establish the reference value of mannose-binding lectin (MBL) serum
      level in children and to investigate the correlation between the polymorphisms of
      MBL2 gene and serum MBL level in healthy Chinese of Han ethnic group and in
      children of Chinese Han ethnic group with recurrent respiratory tract infections
      (RRTI), the concentration of oligomerized MBL was measured by enzyme-linked
      immunosorbent assay, and MBL2 gene polymorphisms were analyzed by restriction
      fragment length polymorphism of polymerase chain reaction and polymerase chain
      reaction-sequence specific primer. The median MBL levels in the 470 normal
      children were 2536 ng/ml, and the P(2.5)-P(97.5) was 161-5,070 ng/ml. Our
      research showed that two promoter polymorphisms at -550, -221 of start codon and
      coding variants at codon 54 of MBL2 gene affected the protein level significantly
      and the most frequent genotype in Hans is HYPA/HYPA. Our results also showed that
      serum MBL level was significantly lower in recurrent respiratory tract infections
      patients compared with healthy controls (Z, -3.04, P = 0.002). The frequency of
      the promoter LXP haplotype and the B allele was significantly higher in RRTI
      patients than in controls (chi (2) 4.05, P < 0.05; OR 1.63, 95%CI 1.01
      approximately 2.62; chi (2) 4.27, P < 0.05; OR 1.94, 95%CI 1.02 approximately
      3.68). CONCLUSION: We have established that the reference value of serum MBL
      level in Chinese aged between 0 and 6 years (161-5,070 ng/ml), and we found that
      LXP and the B are risk factors for RRTI.

PMID- 19169710
TI  - Expression and characterization of aspartic protease gene in eggs and larvae
      stage of Ancylostoma caninum.
AB  - Hookworm infection is still a public health problem in developing countries.
      Aspartic protease plays an important role in parasite invasion and migration in
      the host. Aspartic protease gene from Ancylostoma caninum has been reported
      (Biochem Biophys Res Commun 227:294-302, 1996), but the activity of Acasp in eggs
      and larvae stage has not been studied. This paper reported the cloning of Acasp,
      expression in Escherichia coli, and characterization in eggs and larval stage.
      The mRNA encoding Acasp was detected using reverse transcriptase polymerase chain
      reaction in L4 and adult worm. A polyclonal antiserum against E. coli expressed
      recombinant Acasp was produced and used to detect and localize the Acasp in
      various developmental stages of A. caninum. Results from Western blot and
      indirect fluorescent immunoassay showed that the Acasp was present in the embryo,
      larvae, as well as in the adult worms. The recombinant Acasp exhibited the
      protease activity by the gelatin gel digestion assay.

PMID- 19169711
TI  - RNA editing: only eleven sites are present in the Physcomitrella patens
      mitochondrial transcriptome and a universal nomenclature proposal.
AB  - RNA editing in mitochondria and chloroplasts of land plants alters the coding
      content of transcripts through site-specific exchanges of cytidines into uridines
      and vice versa. The abundance of RNA editing in model plant species such as rice
      or Arabidopsis with some 500 affected sites in their organelle transcripts
      hinders straightforward approaches to elucidate its mechanisms. The moss
      Physcomitrella patens is increasingly being appreciated as an alternative plant
      model system, enhanced by the recent availability of its complete chloroplast,
      mitochondrial, and nuclear genome sequences. We here report the transcriptomic
      analysis of Physcomitrella mitochondrial mRNAs as a prerequisite for future
      studies of mitochondrial RNA editing in this moss. We find a strikingly low
      frequency of RNA editing affecting only eleven, albeit highly important, sites of
      C-to-U nucleotide modification in only nine mitochondrial genes. Partial editing
      was seen for two of these sites but no evidence for any silent editing sites
      (leaving the identity of the encoded amino acid unchanged) as commonly observed
      in vascular plants was found in Physcomitrella, indicating a compact and
      efficient organization of the editing machinery. Furthermore, we here wish to
      propose a unifying nomenclature to clearly identify and designate RNA editing
      positions and to facilitate future communication and database annotation.

PMID- 19169713
TI  - Increasing abundance of soil fungi is a driver for (15)N enrichment in soil
      profiles along a chronosequence undergoing isostatic rebound in northern Sweden.
AB  - Soil organic material (SOM) is usually enriched in (15)N in deeper soil layers.
      This has been explained by discrimination against the heavier isotope during
      decomposition or by the accumulation of (15)N-enriched microbial biomass versus
      plant biomass in older SOM. In particular, ectomycorrhizal (EM) fungi have been
      suggested to accumulate in old SOM since this group is among the most (15)N
      enriched components of the microbial community. In the present study we
      investigated the microbial community in soil samples along a chronosequence
      (7,800 years) of sites undergoing isostatic rebound in northern Sweden. The
      composition of the microbial community was analyzed and related to the delta(15)N
      and delta(13)C isotope values of the SOM in soil profiles. A significant change
      in the composition of the microbial community was found during the first 2,000
      years, and this was positively related to an increase in the delta(15)N values of
      the E and B horizons in the mineral soil. The proportion of fungal phospholipid
      fatty acids increased with time in the chronosequence and was positively related
      to the (15)N enrichment of the SOM. The increase in delta(13)C in the SOM was
      much less than the increase in delta(15)N, and delta(13)C values in the mineral
      soil were only weakly related to soil age. The C:N ratio and the pH of the soil
      were important factors determining the composition of the microbial community. We
      suggest that the N being transported from the soil to aboveground tissue by EM
      fungi is a driver for (15)N enrichment of soil profiles.

PMID- 19169714
TI  - Detection by multiplex ligation-dependent probe amplification of large deletion
      mutations in the COL4A5 gene in female patients with Alport syndrome.

PMID- 19169712
TI  - Association of Y chromosome haplogroup I with HIV progression, and HAART outcome.
AB  - The host genetic basis of differential outcomes in HIV infection, progression,
      viral load set point and highly active retroviral therapy (HAART) responses was
      examined for the common Y haplogroups in European Americans and African
      Americans. Accelerated progression to acquired immune deficiency syndrome (AIDS)
      and related death in European Americans among Y chromosome haplogroup I (Y-I)
      subjects was discovered. Additionally, Y-I haplogroup subjects on HAART took a
      longer time to HIV-1 viral suppression and were more likely to fail HAART. Both
      the accelerated progression and longer time to viral suppression results observed
      in haplogroup Y-I were significant after false-discovery-rate corrections. A
      higher frequency of AIDS-defining illnesses was also observed in haplogroup Y-I.
      These effects were independent of the previously identified autosomal AIDS
      restriction genes. When the Y-I haplogroup subjects were further subdivided into
      six I subhaplogroups, no one subhaplogroup accounted for the effects on HIV
      progression, viral load or HAART response. Adjustment of the analyses for
      population stratification found significant and concordant haplogroup Y-I
      results. The Y chromosome haplogroup analyses of HIV infection and progression in
      African Americans were not significant. Our results suggest that one or more loci
      on the Y chromosome found on haplogroup Y-I have an effect on AIDS progression
      and treatment responses in European Americans.

PMID- 19169715
TI  - Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction
      in the newborn rabbit.
AB  - Acute normocapnic hypoxemia can cause functional renal insufficiency by
      increasing renal vascular resistance (RVR), leading to renal hypoperfusion and
      decreased glomerular filtration rate (GFR). Insulin-like growth factor 1 (IGF-1)
      activity is low in fetuses and newborns and further decreases during hypoxia. IGF
      1 administration to humans and adult animals induces pre- and postglomerular
      vasodilation, thereby increasing GFR and renal blood flow (RBF). A potential
      protective effect of IGF-1 on renal function was evaluated in newborn rabbits
      with hypoxemia-induced renal insufficiency. Renal function and hemodynamic
      parameters were assessed in 17 anesthetized and mechanically ventilated newborn
      rabbits. After hypoxemia stabilization, saline solution (time control) or IGF-1
      (1 mg/kg) was given as an intravenous (i.v.) bolus, and renal function was
      determined for six 30-min periods. Normocapnic hypoxemia significantly increased
      RVR (+16%), leading to decreased GFR (-14%), RBF (-19%) and diuresis (-12%), with
      an increased filtration fraction (FF). Saline solution resulted in a worsening of
      parameters affected by hypoxemia. Contrarily, although mean blood pressure
      decreased slightly but significantly, IGF-1 prevented a further increase in RVR,
      with subsequent improvement of GFR, RBF and diuresis. FF indicated relative
      postglomerular vasodilation. Although hypoxemia-induced acute renal failure was
      not completely prevented, IGF-1 elicited efferent vasodilation, thereby
      precluding a further decline in renal function.

PMID- 19169716
TI  - Differential effects of AM fungal isolates on Medicago truncatula growth and
      metal uptake in a multimetallic (Cd, Zn, Pb) contaminated agricultural soil.
AB  - Toxic metal accumulation in soils of agricultural interest is a serious problem
      needing more attention, and investigations on soil-plant metal transfer must be
      pursued to better understand the processes involved in metal uptake. Arbuscular
      mycorrhizal (AM) fungi are known to influence metal transfer in plants by
      increasing plant biomass and reducing metal toxicity to plants even if diverging
      results were reported. The effects of five AM fungi isolated from metal
      contaminated or non-contaminated soils on metal (Cd, Zn) uptake by plant and
      transfer to leachates was assessed with Medicago truncatula grown in a
      multimetallic contaminated agricultural soil. Fungi isolated from metal
      contaminated soils were more effective to reduce shoot Cd concentration. Metal
      uptake capacity differed between AM fungi and depended on the origin of the
      isolate. Not only fungal tolerance and ability to reduce metal concentrations in
      plant but also interactions with rhizobacteria affected heavy metal transfer and
      plant growth. Indeed, thanks to association with nodulating rhizobacteria, one
      Glomus intraradices inoculum increased particularly plant biomass which allowed
      exporting twofold more Cd and Zn in shoots as compared to non-mycorrhizal
      treatment. Cd concentrations in leachates were variable among fungal treatments,
      but can be significantly influenced by AM inoculation. The differential
      strategies of AM fungal colonisation in metal stress conditions are also
      discussed.

PMID- 19169717
TI  - Short-term consequences of slash-and-burn practices on the arbuscular mycorrhizal
      fungi of a tropical dry forest.
AB  - Rates of land conversion from forest to cultivated land by slash-and-burn
      practices are higher in tropical dry forest (TDF) than any other Neotropical
      forest type. This study examined the short-term consequences of the slash-and
      burn process on arbuscular mycorrhizal fungi (AMF). We expected that slash-and
      burn would reduce mycorrhizal colonization and propagules and change species
      richness and composition. Soil and root samples were taken from TDF control and
      pasture plots originated after slash-and-burn at four dates during the year of
      conversion to examine species composition, spore abundance, and infective
      propagules. Additionally, spore abundance and viability and viable intraradical
      colonization were measured twice during the second year after conversion. Forest
      and pasture plots maintained similar species richness and an overall 84%
      similarity during the first year after conversion. Infective propagules were
      reduced in pasture plots during the first year after slash-and-burn, whereas
      spore abundance and intraradical colonization remained similar in TDF and pasture
      plots both years of the study. Our results suggest, contrary to the expected,
      that forest conversion by means of slash-and-burn followed by cultivation
      resulted in few immediate changes in the AMF communities, likely because of the
      low heat conductivity of the soil and rapid combustion of plant residues.

PMID- 19169718
TI  - Letter to the editors.

PMID- 19169719
TI  - Three-year clinical prospective evaluation of zirconia-based posterior fixed
      dental prostheses (FDPs).
AB  - This clinical study evaluated posterior three-unit fixed dental prostheses (FDPs)
      made of zirconia substructures veneered with pressable glass-ceramic. Nineteen
      patients received 21 FDPs replacing either the second premolar, first molar, or
      second molar. The FDPs were cemented with glass ionomer. Recall examinations were
      performed every 12 months. The mean service time of the FDP was 40 months. At 30
      months, one maxillary FDP exhibited zirconia framework fracture at a thinned
      occlusal area of the abutment. Loss of retention led to the removal of one FDP
      after 38 months. The Kaplan-Meier survival probability was 90.5% after 40 months
      for all types of failures and 95.2% concerning framework fractures. The
      overpressing technique appears to be reliable in terms of the veneering material.
      However, one framework fracture was observed in this study.

PMID- 19169721
TI  - Human beta-defensins--at the front line of the peritonsillar abscess.
AB  - Antimicrobial proteins like human beta-defensins 1-4 (hBD1-4) protect the surface
      of organs against different bacteria. Little is still known about these proteins
      within an abscess formation. The purpose of this study was to analyse and
      describe the distribution of the antimicrobial proteins hBD 1-4 within the
      peritonsillar abscess. A total of 17 peritonsillar abscesses were analysed.
      Immunohistochemical stainings were performed, characteristic pictures were taken,
      and the mean colour intensity was measured using a specific imaging software. A
      statistical analysis compared the areas of interest of the specific protein
      staining with the one of the control staining. A total of 4,573 areas of
      interests were measured. A significantly stronger expression was detected for
      hBD1 in the surface epithelium, crypt, epithelium of the crypt, lymphocytic cap,
      and abscess formation in the hBD1 staining in comparison to the control samples.
      But there was no significance in the specific hBD1-protein expression in
      comparison to the control samples in the lymphoid follicle and in the germinal
      centre. There was a significantly stronger hBD2, hBD3, and hBD4 expression in all
      areas of interest for the specifics stainings in comparison to the control
      samples. In conclusion, we developed different scenarios which could lead to a
      peritonsillar abscess formation.

PMID- 19169720
TI  - Comparison of community-associated methicillin-resistant Staphylococcus aureus
      from teaching hospitals in London and the USA, 2004-2006: where is USA300 in the
      UK?
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is
      increasingly common in the USA, but rare in the UK. We compared CA-MRSA from the
      UK and USA to examine differences in the molecular epidemiology. We investigated
      patients presenting with MRSA in the first 72 h of hospital admission or in out
      patient settings in a UK and a US hospital from January 2004 to March 2006.
      Fluoroquinolone susceptibility was used as a screening marker to select
      presumptive CA-MRSA. One hundred and eighteen and 49 such strains were
      identified, representing a prevalence of 0.1 and 0.2 isolates per 1,000 patient
      days in the UK and US respectively. Panton-Valentine leukocidin (PVL)-positive
      ST8-IVa (USA300)-type strains predominated among 43 surviving US isolates,
      whereas PVL-negative ST1-IVa predominated among 71 surviving UK isolates. There
      are striking differences between the molecular epidemiology of CA-MRSA in UK and
      US hospitals, which may have implications for control.

PMID- 19169722
TI  - Corona patterns around inclusions in freely suspended smectic films.
AB  - We discuss the structure and physical origin of corona patterns observed around
      solid or liquid spherical inclusions in freely suspended smectic films. Such
      patterns are observed when droplets or solid beads of micrometer size are sprayed
      onto the films. They are found in the smectic C phase and in the smectic A phase
      above such a smectic C phase, but disappear, for example, at the transition into
      a lower-temperature smectic B phase. We show that these structures are equivalent
      to splay domains found in the meniscus of freely suspended films, originating
      from surface-induced spontaneous splay.

PMID- 19169723
TI  - Optimal strokes for axisymmetric microswimmers.
AB  - We present a theory for low-Reynolds-number axisymmetric swimmers and a general
      strategy for the computation of strokes of maximal efficiency. An explicit
      equation characterizing optimal strokes is derived, and numerical strategies to
      obtain solutions are discussed. The merits of this approach are demonstrated by
      applying it to two concrete examples: the three linked spheres of Najafi and
      Golestanian and the pushmepullyou of Avron, Kenneth, and Oakmin.

PMID- 19169724
TI  - Is the clinical presentation different between men and women admitting to the
      sleep laboratory?
AB  - OBJECTIVES: Sleep and sleep disorders are different in several important ways
      between men and women. We aimed to investigate gender differences in initial
      symptoms and associating medical diseases of patients admitting to our sleep
      clinic. METHODS: Ninety-one patients, 20 women (22%) and 71 men (78%), admitting
      consecutively to the sleep clinic were studied. A detailed sleep and medical
      history of the patients was recorded. All patients were questioned for Epworth
      Sleepiness Scale (ESS) and underwent an entire night of diagnostic
      polysomnography. Apnea-hypopnea index (AHI) was identified as the total number of
      apnea and hypopnea per hour of sleep. Hypopnea was defined as a decrease of
      airflow by at least 50% and desaturations were defined as >or=4% decrease in
      oxygen saturation. RESULTS: The mean values for age, body mass index, blood
      pressures and ESS score did not significantly differ between men and women, but
      AHI (events/h) was significantly higher in men (29.1 +/- 22.7) than women (17.9
      +/- 17.7, p < 0.05). Snoring was the most common symptom in both men (95%) and
      women (90%). Among the main presenting complaints, only morning headache (12 of
      women 60%, 31 of men 43%, p = 0.04) and dry mouth on awakening (ten of women 50%,
      57 of men 80%, p = 0.02) showed a significant difference between the two genders,
      while among the medical diseases only hypothyroidism (four of women 20% and three
      of men 4%, p = 0.03) and depression (nine of women 45% and 16 of men 22%, p =
      0.02) were seen as statistically higher in women than in men. CONCLUSIONS:
      Primary care physicians should be aware of obstructive sleep apnea (OSA) in women
      and the importance of referring women for sleep studies when they complain of
      symptoms associated with OSA, even if other non-specific symptoms such as morning
      headaches are reported. Also, hypothyroidism and depression are accompanied with
      sleep disorders especially in women.

PMID- 19169726
TI  - Effects of adipocyte-secreted factors on cell cycle progression in HT29 cells.
AB  - BACKGROUND: Obesity is a chronic sub-inflammatory condition which is a risk
      factor for several cancer diseases, e.g. colon cancer. Adipose tissue secretes
      biologically active factors like leptin with a known pro-inflammatory or
      mitogenic activity. Both, chronic inflammation and an increased cell
      proliferation are considered to play an important role in colon carcinogenesis.
      Diverse phytochemicals were shown to have cell growth inhibiting effects. AIM OF
      THE STUDY: The aim was to investigate whether adipocytes could mediate a
      proliferative capacity to HT29, a human colon adenocarcinoma cell line, and
      whether phytochemicals could modulate this effect. METHODS: Infranatants of
      adipocyte cultures from different donors were prepared and the effects of those
      conditioned adipocyte media (CAM) on HT29 cell growth were measured.
      Additionally, cell cycle progression was analyzed by flow cytometry after CAM
      treatment and ERK 1/2 phosphorylation was analyzed. RESULTS: CAM from a subgroup
      of adipose tissue donors stimulated HT29 cell growth, whereas others did not.
      This effect seems to be mediated via the ERK 1/2 pathway. Furthermore, CAM caused
      changes in cell cycle distribution with a shift of HT29 cells from G1- into the S
      phase. This effect could be mimicked by leptin (1 nM). Co-incubation of CAM
      treated HT29 cultures with beta-carotene or EGCG did not have a significant
      impact on cell cycle progression, whereas genistein (30 microM) tended to inhibit
      the CAM-stimulated transition of cells into the S-phase. CONCLUSION: This study
      confirmed the mitogenic activity of leptin in HT29 cells, although leptin
      secretion from adipocytes is not likely to be responsible for CAM-stimulated cell
      growth in our test system. The investigated phytochemicals seem to have only a
      minor influence on CAM-mediated cell cycle progression.

PMID- 19169727
TI  - Production of L-tryptophan-derived catabolites in hepatocytes from streptozotocin
      induced diabetic rats.
AB  - BACKGROUND: Recently the L-tryptophan (Trp) metabolites such as L
      kynurenine(Kyn), L-kinurenic acid, quinolinic acid (QA) and picolinic acid (PA)
      have been shown physiologically important in central nervous and immune system,
      and various enzyme activities concerning their production were reported to be
      affected by insulin-dependent diabetes mellitus. However, the states of these
      metabolites in diabetes have not been clarified enough yet. AIM OF STUDY: The
      present study was performed to make clear the states of the productions of L-Kyn,
      QA, PA and nicotinamide (Nam) in vitro in the hepatocytes prepared from
      streptozotocin (STZ)-induced diabetic rats using [5-3H]L-Trp. METHODS: The
      diabetic model rats were made by STZ injection (60 mg/kg) and the hepatocytes
      isolated from the rats were incubated with [5-3H]L-Trp. The amounts of
      metabolites derived from L-Trp were determined by the isotope-dilution methods.
      RESULTS: The alpha-amino-beta-carboxymuconate-epsilon-semiarldehyde decarboxylase
      (ACMSD) mRNA level in the diabetic group was greatly higher than that in the
      control group. In the STZ-induced diabetes group, the amount of [5-3H]L-Trp
      converted to tritiated water, L-Kyn or QA were found to be more than 3 times of
      that in the control group, respectively. The produced amounts of PA and Nam were
      not significantly different between the diabetic and the control groups.
      CONCLUSIONS: It is suggested that STZ-diabetes mellitus causes augmentations of
      both L-Kyn and QA generations but not those of PA and Nam in liver, indicating
      the possibility that the immune and neuronal systems of insulin dependent
      diabetes mellitus would be influenced by the increased amounts of LKyn and QA but
      not by those of PA and Nam.

PMID- 19169729
TI  - [Dear readers].

PMID- 19169730
TI  - [Single- and dual-chamber ICDs: Are there still significant differences compared
      to pacemakers with regard to implantation and follow-up?].
AB  - Due to bulky generator size, abdominal pocket preparation and epicardial
      defibrillator lead placement, cardioverter-defibrillator (ICD) implantation was
      initially an extensive surgical intervention, which had to be performed in the
      operating room by cardiac surgeons under general anesthesia. The development of
      transvenously applicable endocardial defibrillator leads rendered thoracotomy
      unnecessary. The decrease in generator size enabled pectoral implantation. As a
      consequence of the simplified surgical procedure, implantation by cardiologists
      or electrophysiologists in the catheterization laboratory under local anesthesia
      and brief deep sedation with preserved spontaneous respiration was made possible.
      As a result, the implantation techniques of ICDs and pacemakers are converging.
      The present article illustrates the still existing significant differences
      between ICD and pacemaker treatment with regard to implantation and follow-up.

PMID- 19169731
TI  - [Sandwiched between the single- and triple-chamber ICD: do we still need the dual
      chamber ICD?].
AB  - Since it has been shown that adverse events are more frequent with dual-compared
      to single-chamber ICDs in patients with heart failure, and since the importance
      of prevention of unnecessary right ventricular pacing and the success of
      biventricular pacing have been demonstrated in numerous studies, the need for
      dual-chamber ICD systems has to be reassessed. The development of these systems
      was accompanied by expectations of improved hemodynamics in patients with
      bradycardia, a reduced incidence of atrial fibrillation, inappropriate therapies,
      and bradycardia-associated ventricular tachyarrhythmias. Single-chamber ICDs
      should be used restrictively and with great caution in patients with (sinus-)
      bradycardia and heart failure, since a relevant proportion of these patients is
      at risk of hemodynamic deterioration. Even if the proportion of patients with
      proven pacemaker syndrome is so small that it does not reach the level of
      statistical significance in large studies, a small percentage of patients with
      hemodynamic deterioration due to VVI pacing is still clinically (and
      economically) intolerable. Since the development of bradycardia or symptomatic
      chronotropic incompetence (e.g., due to amiodarone) is difficult to predict, it
      seems reasonable to use the indication for dualchamber systems liberally.
      However, the systematic prevention of unnecessary right ventricular pacing is
      crucial if dual-chamber ICDs are used. If advanced tachycardia discrimination
      algorithms and careful, individual programming are used, dual-chamber ICDs are
      superior in the prevention of inappropriate therapies. Additionally, dualchannel
      electrograms allow a more reliable interpretation of stored tachycardia episodes.
      In summary, dual-chamber systems represent a valuable improvement of ICD therapy
      but require thorough programming to convey their advantage.

PMID- 19169732
TI  - [Is resynchronization therapy necessary when optimizing right ventricular
      stimulation?].
AB  - Cardiac resynchronization therapy (CRT) using biventricular stimulation is
      hampered by coronary venous imponderabilities, complex implantation procedures,
      technical malfunctions and complications as well as disappointing responder
      rates. Despite its pathophysiological soundness and some initial success, the use
      of AV sequential pacing for the treatment of heart failure has been abandoned
      because right ventricular (RV) apical stimulation may be detrimental for cardiac
      mechanics, may worsen heart failure and may increase mortality. Attempts at
      avoiding desynchronizing effects and improving hemodynamics by pacing from
      alternative RV sites have been numerous but not convincing. Whether patients with
      left ventricular dysfunction or overt heart failure may benefit from pacing the
      RV outflow tract or septum, from dual site RV or His bundle stimulation instead
      of left ventricular based resynchronization is the topic of this review.

PMID- 19169733
TI  - [Upgrading to biventricular pacing: indications and procedural challenges].
AB  - Upgrading RV pacing systems to biventricular resynchronization modalities is a
      promising option for paced patients with worsening heart failure. The potentially
      favorable effect of upgrading has been demonstrated in several, non-randomized
      trials. Selection of eligible patients and technical aspects of the procedure are
      described. The most common procedure-related complications are reported.

PMID- 19169734
TI  - [Role of right heart failure in cardiac resynchronization].
AB  - During recent years cardiac resynchronization has become an important tool in the
      treatment of patients with signs and symptoms of heart failure and desynchronized
      contraction of the left ventricle. Among patients with heart failure, right
      ventricular involvement can occur because the underlying disease affects both
      ventricles or because the reduction of left ventricular function impairs the
      right ventricular function by altered coupling and increased right ventricular
      afterload. Irrespective of the underlying cause the reduction of right
      ventricular function confers an adverse prognosis that is further aggravated by
      the presence of pulmonary hypertension. The present article describes the
      relevance of reduced right ventricular function for the clinical syndrome of
      heart failure, the role of right ventricular resynchronization in patients with
      predominant right heart failure and the possible effects of left ventricular
      resynchronization on a preexisting impairment of right ventricular function.

PMID- 19169735
TI  - Mitral valve regurgitation and left ventricular systolic dysfunction: corrective
      surgery or cardiac resynchronization therapy?
AB  - Mitral regurgitation (MR) can be found in a sizeable percentage of patients with
      chronic congestive heart failure (CHF) and systolic left ventricular (LV)
      dysfunction despite a structurally normal valve. This functional or secondary
      regurgitation results from a dysbalance between closing and opening forces on the
      mitral leaflets due to reduced LV contractility, geometric distortion of the
      subvalvular apparatus, and global dilatation of the left ventricle and the mitral
      annulus. MR in LV dysfunction has a negative impact on both symptoms and
      prognosis. Surgical correction of secondary MR remained controversial although it
      was found to be technically feasible and to provide symptomatic benefit in some
      (mostly) mono-center series. Cardiac resynchronization therapy (CRT) was also
      found to improve secondary mitral regurgitation. However, the prediction in which
      patient significant secondary MR will improve with CRT is largely unresolved. The
      following paper reviews the available data concerning the two major
      interventional options for significant secondary MR in patients with CHF and
      systolic LV dysfunction, i.e. mitral valve surgery vs. CRT, and describes our
      institutional approach to this problem.

PMID- 19169736
TI  - [CRT in atrial fibrillation--methodical and apparatus options in decision
      making].
AB  - Heart failure and atrial fibrillation often coexist, especially with increasing
      degree of heart failure severity. Under this constellation, the advantage of
      cardiac resynchronization therapy (CRT) is still under discussion and displayed
      as an unresolved problem in the guidelines for cardiac stimulation and
      resynchronization. If ventricular desynchronization can be documented and
      response to CRT can be expected, the challenge is to interoperatively seek the
      best left ventricular electrode position and to postoperatively optimize the
      device in order to achieve the best therapy performance. This situation
      encourages the development of individualized methods and to utilize innovative
      apparatus features in order to consolidate individual decisions and to optimize
      CRT in heart failure with atrial fibrillation.

PMID- 19169737
TI  - [Improving left ventricular contractility by stimulation during the absolute
      refractory period--cardiac contractility modulation (CCM)].
AB  - Cardiac contractility modulation (CCM) is a treatment option for patients with
      systolic ventricular dysfunction, independent of QRS duration, moderate to severe
      systolic heart failure and symptoms despite optimal medical therapy. In contrast
      to cardiac resynchronization therapy (CRT) which has been an established therapy
      in patients with wide QRS and ventricular asynchrony, CCM can enhance cardiac
      contractility in patients independent of QRS duration. Whereas inotropic drugs
      increase oxygen demand, CCM works without additional myocardial oxygen need and
      without reference to asynchrony. Non-excitatory signals applied during the
      absolute refractory period have been shown to enhance the strength of left
      ventricular contraction in animals and humans with heart failure probably due to
      normalization of myocardial gene expression. Several multicenter studies have
      demonstrated safety and efficacy of CCM in patients with medically refractory
      heart failure. We describe the specific technical aspects and conditions in
      clinical application of CCM.

PMID- 19169738
TI  - Effect of pH, EDTA, and anions on heavy metal toxicity toward a bioluminescent
      cyanobacterial bioreporter.
AB  - The bioavailability and therefore toxicity of a metal depends on the chemical
      species present in a particular environment. We evaluated the effect of a series
      of factors that could potentially modify metal speciation on the toxicity of Hg,
      Cu, Zn, and Cd toward a recombinant strain of the freshwater cyanobacterium
      Anabaena sp. PCC 7120 with cloned lux operon of luminescent terrestrial bacterium
      Photorhabdus luminescens. The strain, denoted as Anabaena CPB4337, showed a high
      constitutive luminescence with no need to add exogenous aldehyde. The tested
      factors were pH, EDTA (as organic ligand), and anions PO(4)(3-), CO(3)(2-), and
      Cl(-). Chemical modeling and correlation analyses were used to predict metal
      speciation and link it with toxicity. In general, metal toxicity significantly
      correlated to the predicted metal free-ion concentration, although Zn-EDTA
      complexes and certain Hg chloro-complexes could also exhibit some toxicity to
      cyanobacteria. An interesting feature of metal toxicity to strain Anabaena
      CPB4337 was that low amounts of PO(4)(3-) and CO(3)(2-) increased metal toxicity;
      this effect could not be related to significant changes in metal speciation and
      could be attributed to a modulating effect of these anions on metal/uptake
      toxicity. The combination of toxicity studies that take into account a range of
      factors that might modulate metal toxicity with chemical modeling to predict
      changes in metal speciation might be useful for interpreting complex toxicity
      data. Finally, this cyanobacterial bioreporter, due to its ecological relevance
      as a primary producer, could be used as a tool for toxicity assessment in
      freshwater environments.

PMID- 19169739
TI  - Accumulation of lead, chromium, and cadmium in muscle of capitan (Eremophilus
      mutisii), a catfish from the Bogota River basin.
AB  - Heavy metal accumulation of lead (Pb), chromium (Cr), and cadmium (Cd) in the
      muscle of the catfish Eremophilus mutisii was studied in 47 specimens, captured
      by anglers in the Bogota River at two sampling sites (Choconta and Suesca) during
      May-October 2005. Water samples were processed for physicochemical and metal
      analyses. Metal accumulation in muscle (wet weight) of specimens at Choconta and
      Suesca showed high levels of Pb (3.4 and 3.1 ppm, respectively), Cr (1.8 and 2.1
      ppm, respectively), and Cd (0.35 and 0.48, respectively). Metal levels in waters
      (ppm) indicated that average Pb (0.028 Choconta, 0.029 Suesca), Fe (0.462
      Choconta, 1.1 Suesca), and Cr (0.113 Choconta) were above the maximum levels
      (MCLs) allowed in drinking waters. No extreme average values were found for pH,
      nitrites, alkalinity, and hardness in the waters. This study showed the
      importance of benthic and nonmigratory species like the capitan to evaluate the
      effects of heavy metals pollution. Further public health implications could be
      derived in the region where this investigation took place due to consumption of
      capitan by people in the area.

PMID- 19169740
TI  - Characterization of bacterial communities associated with organic aggregates in a
      large, shallow, eutrophic freshwater lake (Lake Taihu, China).
AB  - Although organic-aggregate-associated bacteria play a pivotal role in microbial
      food webs and in the cycling of major elements, their community composition and
      diversity have not been extensively studied, especially in shallow freshwater
      systems. This study is among the first to explore intra-lake horizontal
      heterogeneity of organic-aggregate-associated bacterial community composition
      (OABC) in the large, shallow, and eutrophic Lake Taihu. During November 2006,
      samples were collected at four locations representing different trophic states
      and food web structures. Regional variability of OABC and diversity were studied
      by amplified ribosomal DNA restriction analysis and comparative analysis of four
      large 16S ribosomal RNA clone libraries. Our results demonstrate that OABC were
      numerically dominated by members of the beta-proteobacteria (19.2-38.6%),
      Bacteroidetes (3.6-20.0%), and alpha-proteobacteria (11.5-19.2%) groups. The
      dominance of the Bacteroidetes group was related to algae-based aggregates.
      Horizontal heterogeneity of OABC exists within habitats, suggesting that the
      trophic state of the water and the physicochemical properties of organic
      aggregates (OA) play a key role. Diverse bacterial communities found on OA were
      substantially different from free-living ones. Comparative statistical analyses
      of the habitats of OA-associated bacteria highlight the potential ecological
      importance of the exchange between OABC and the surrounding planktonic community.
      Lastly, we found at least 45% of sequences closely related to ones previously
      found in soils, sludge, sediments, and other habitats. This demonstrates that
      microorganisms from terrestrial and sediment habitats are an important component
      of OA.

PMID- 19169741
TI  - Peritonectomy for peritoneal carcinomatosis: long-term outcomes from a single
      Brazilian institution.
AB  - BACKGROUND: The objective of this study was to evaluate the long-term outcomes of
      a single institution, Hospital Sirio-Libanes in Sao Paulo, Brazil, regarding the
      treatment of peritoneal carcinomatosis. METHODS: Between October 2002 and October
      2006, 46 consecutive patients were treated with radical cytoreduction and
      hyperthermic peritoneal chemotherapy. There were 21 patients with peritoneal
      surface malignancy (PSM) from colorectal origin (among whom 8 had an appendiceal
      primary), 15 with ovarian carcinomas, 2 with primary peritoneal mesotheliomas,
      and 8 with other cancers. The median age was 49 years (range 18-77 years). All
      patients were followed for a median of 20 months. Demographic data, tumor
      histology, the peritoneal carcinomatosis index (PCI), operative procedures
      (extension of resection, lymphadenectomy), and hyperthermic intraperitoneal
      chemotherapy (HIPEC) characteristics (drugs, temperature, duration) were
      prospectively recorded. Perioperative mortality and morbidity and the long-term
      outcome were assessed. RESULTS: Complete cytoreduction was achieved in 45
      patients. The median PCI was 11, and the mean operating time was 17 h. There were
      no procedure-related deaths, but major morbidity was observed in 52% and included
      fistulas, abscesses, and hematologic complications. The overall Kaplan-Meier 4
      year estimated survival was 56%. Among patients with PSM from colorectal
      carcinoma, the estimated 3-year survival was 70%. Nine (42%) patients had a
      recurrence, three with peritoneal disease. The median disease-free-interval was
      16 months. The ovarian cancer patients had an estimated 4-year survival rate of
      75% and median disease-free survival duration of 21 months. CONCLUSIONS:
      Cytoreductive surgery with HIPEC may improve survival of selected patients with
      peritoneal carcinomatosis, with acceptable morbidity.

PMID- 19169742
TI  - Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract.
AB  - Despite the increasing interest in other classes of small RNAs, microRNAs
      (miRNAs) remain the most widely investigated and have been shown to play a role
      in a number of different processes in mammals. Many studies investigating miRNA
      function focus on the processing enzyme Dicer1, which is an RNAseIII protein
      essential for the biogenesis of active miRNAs through its cleavage of precursor
      RNA molecules. General deletion of Dicer1 in the mouse confirms that miRNAs are
      essential for development because embryos lacking Dicer1 fail to reach the end of
      gastrulation. Here we investigate the role of Dicer1 in urogenital tract
      development. We utilised a conditional allele of the Dicer1 gene and two Cre
      expressing lines, driven by HoxB7 and Amhr2, to investigate the effect of Dicer1
      deletion on both male and female reproductive tract development. Data presented
      here highlight an essential role for Dicer1 in the correct morphogenesis and
      function of the female reproductive tract and confirm recent findings that
      suggest Dicer1 is required for female fertility. In addition, HoxB7:Cre-mediated
      deletion in ureteric bud derivatives leads to a spectrum of anomalies in both
      males and females, including hydronephrotic kidneys and kidney parenchymal cysts.
      Male reproductive tract development, however, remains largely unaffected in the
      absence of Dicer1. Thus, Dicer1 is required for development of the female
      reproductive tract and also normal kidney morphogenesis.

PMID- 19169743
TI  - Developmental methylation program and concerted expression of Stx11 in mouse
      tissues.
AB  - The human 6q24 region is involved in growth and development, transient neonatal
      diabetes (TND), cancer, and metabolic dysfunction. To further characterize this
      region, the developmental status of DNA methylation and expression of Zac1 and
      Stx11 genes located within the mouse 10A1 region ortholog of human 6q24 were
      determined. In mice, imprinted Zac1 and Stx11 were highly expressed at the end of
      fetal development but downregulated at 4 and 11 weeks in brain, pancreas, and
      heart. Postnatal Zac1 downregulation was independent from promoter methylation of
      the expressed allele, suggesting the mediation of age-dependent chromatin
      remodeling. Stx11 nonpromoter CpG island was methylated de novo from E18 to 1
      year with tissue-specific kinetics. The high conservation in vertebrates of Stx11
      CpG2 is suggestive of an important regulatory function in age-related regional
      epigenetic state and/or chromatin configuration. Stx11 alleles were unequally
      expressed in F1 mice tissues, reflecting the influence of cis-regulatory factors
      on its expression. These data suggest the presence of a methylation domain and a
      coordinated gene expression pattern in multiple tissues. Methylation variation
      and allelic regulation of expression may underlie genetic diversity and
      contribute to disease susceptibility at the 6q24 locus in humans.

PMID- 19169744
TI  - Multimedia manuscript. NOTES retroperitoneal transvaginal distal pancreatectomy.
AB  - BACKGROUND: The retroperitoneal approach preserves the peritoneal cavity and its
      envelope. The benefits of laparoscopic retroperitoneal approach to the kidney and
      the adrenal gland are well known. The pancreas may represent another potential
      target. Whereas NOTES transperitoneal distal pancreatectomy has been reported,
      the retroperitoneal approach, which may combine the advantages of peritoneal
      preservation with those of no scar surgery, has never been explored. We report
      the feasibility of NOTES transvaginal retroperitoneal pancreatectomy in a porcine
      model. METHODS: With the pig supine, under general anesthesia, a 10-mm posterior
      colpotomy was performed with a needle-knife operated through a flexible 12-mm,
      double-channel endoscope (Karl Storz). A retroperitoneal tunnel was created with
      blunt dissection up to the left kidney with progressive visualization of the left
      iliac vessels, ureter, and abdominal aorta. To reach the posterior aspect of the
      pancreas, a space was opened medial to the upper renal pole dividing the Gerota's
      fascia. The tail of pancreas was mobilized with blunt and sharp dissection, using
      monopolar cautery. Once the distal pancreas was dissected free, it was secured
      using a polypropylene endoscopic loop and then resected with an endoscopic snare
      (Olympus). RESULTS: The procedure was successfully accomplished by a totally
      NOTES approach in five pigs, with a mean operative time of 118 (range, 105-185)
      minutes with no intraoperative complications and no injury to any retroperitoneal
      structure. CONCLUSIONS: The pancreas is accessible by a transvaginal
      retroperitoneal NOTES approach. Human cadavers studies are necessary to confirm
      the validity of this model and to explore the need for specific technological
      developments, such as flexible stapling devices, to improve the safety of
      pancreatic resection.

PMID- 19169745
TI  - Laparoscopic sleeve gastrectomy versus intragastric balloon: a case-control
      study.
AB  - AIM: To compare the efficacy of laparoscopic sleeve gastrectomy (LSG) and
      BioEnterics intragastric balloon (BIB) to lose weight and comorbidities after 12
      months of follow-up before a more invasive bariatric procedure. METHODS: From
      January 2004 to December 2006, 40 patients underwent laparoscopic sleeve
      gastrectomy (LSG) as a first step in biliopancreatic diversion with duodenal
      switch. Controls (n = 80) were selected based on charts of patients who, during
      the same period, underwent BioEnterics intragastric balloon therapy. In both
      groups we considered: length of procedure, hospital stay, intraoperative or
      endoscopic complications, postoperative or postendoscopic complications,
      comorbidities at baseline, after 6 months (time of BIB removal), and after 12
      months from baseline, and weight loss parameters [weight in kg, percentage excess
      weight less (%EWL), body mass index (BMI), and percentage excess BMI loss
      (%EBL)]. Results are expressed as mean +/- standard deviation. RESULTS:
      Mortality, intra- and postoperative complications (in LSG group), and intra- and
      postendoscopic complications (in BIB group) were absent. Mean operative time in
      the LSG group was 120 +/- 40 (range 60-200) min. Mean positioning time for BIB
      was 15 +/- 5 (range 10-25) min. BMI at baseline was 54.1 +/- 2.9 (range 45.1
      55.9) kg/m(2) and 54.8 +/- 2.5 (range 45.1-56.2) kg/m(2) in BIB and LSG groups,
      respectively. At 6-month follow-up, mean BMI was 46.2 +/- 3.5 and 45.3 +/- 5.5
      kg/m(2) in the BIB and LSG patients, respectively [p = not significant (ns)].
      After 12 months BIB patients regained BMI, even if strictly followed with a diet
      regimen, while LSG patients continued to lose weight. Significant differences
      between groups were absent for the comorbidities considered. CONCLUSIONS:
      Laparoscopic sleeve gastrectomy and BioEnterics intragastric balloon are two
      valid options for producing weight loss as a first-step procedure. LSG has all
      the related risks of general anesthesia, laparoscopic surgery, and digestive
      anastomosis, whereas BIB presents a very low rate of minor complications, such as
      psychological intolerance. For all these reasons, at this time, BIB is considered
      a better option than LSG as a first-step procedure in the short term (12 months).

PMID- 19169746
TI  - Surg Endosc 2008;22:1620-1624. Biochemical predictors of common bile duct (CBD)
      stones.

PMID- 19169747
TI  - Combined laparoscopic-endoscopic resections of colorectal polyps: 10-year
      experience and follow-up.
AB  - BACKGROUND: Large, colorectal polyps or those that are difficult to access may be
      unamenable to conventional snare polypectomy and may require surgical resection.
      This study was designed to evaluate the resection of such lesions by the use of
      combined laparoscopic-endoscopic resections (CLER). METHODS: Patients who had
      received CLER for colorectal polyps between January 1997 and December 2006 were
      identified from a prospectively maintained database. Patients with biopsies
      consistent with invasive cancer were excluded from the combined approach.
      Baseline characteristics, surgical, pathological, postoperative, and follow-up
      data of patients and lesions were reviewed. RESULTS: A total of 146 consecutive
      patients underwent CLER for 154 lesions, and 120 (82%) patients underwent local
      excision (i.e., laparoscopy-assisted endoscopic resection, endoscopy-assisted
      wedge resection, and endoscopy-assisted transluminal resection). Twenty-six (18%)
      patients received endoscopy-assisted segmental colon resection. Conversion rate
      was 5% and intraoperative complications occurred in two patients (1%). Major
      postoperative complications occurred in five patients (3%), necessitating
      surgical reintervention in four of them. Follow-up colonoscopy revealed
      metachronous adenomas in 33 patients, of which 8 patients showed macroscopic or
      microscopic characteristics of advanced lesions. One patient, who had been
      converted to open resection because of incomplete laparoscopic resection of an
      adenoma, developed relapse of the initial adenoma and was successfully treated
      with repeat CLER accounting for a local recurrence rate of 0.9%. CONCLUSIONS:
      Combined laparoscopic-endoscopic resection is an efficient, safe, and minimally
      invasive alternative to open resection for selected patients with difficult
      polyps, but it should be restricted to benign disease.

PMID- 19169748
TI  - The use of medication after laparoscopic antireflux surgery.
AB  - BACKGROUND: Laparoscopic antireflux surgery (LARS) significantly improves
      symptoms of gastro-esophageal reflux disease (GERD) and quality of life.
      Nevertheless, 14-62% of patients report using antisecretory medication after
      surgery, although only a tiny percentage has proven recurrence of GERD. We sought
      to determine symptoms of GERD, quality of life, and use of medication before and
      after LARS, and to compare our findings with those from previous studies.
      METHODS: Five hundred fifty-three patients with GERD who underwent LARS were
      evaluated before and at 1 year after surgery. After surgery, multidisciplinary
      follow-up care was provided for all patients by surgeons, psychologists,
      dieticians, and speech therapists. RESULTS: Symptoms of GERD and quality of life
      improved significantly and only 4.2% of patients still required medication after
      surgery [proton pump inhibitors (PPI) (98.4 vs. 2.2%; p < 0.01), prokinetics (9.6
      vs. 1.1%; p < 0.01), and psychiatric medication (8 vs. 1.6%; p < 0.01)].
      CONCLUSION: LARS significantly reduced medication use at 1-year follow-up.
      However, these effects might be attributed, in part, to the multidisciplinary
      follow-up care. Further studies are therefore required to investigate which
      patients may benefit from multidisciplinary follow-up care and whether its
      selective application may reduce the need for medication after LARS.

PMID- 19169749
TI  - True single-port appendectomy: first experience with the "puppeteer technique".
AB  - BACKGROUND: Laparoscopic appendectomy is one of the most commonly performed
      minimally invasive surgeries worldwide. In recent years, successful attempts to
      reduce the number of the traditionally used three ports have been reported.
      Specifically, two-port techniques, hybrid approaches, and single-port assisted
      techniques have been described. METHODS: In this case series, the author
      describes for the first time a successful and uncomplicated true single-port
      appendectomy (TSPA) technique. Between July and December of 2007, 14 consecutive
      patients were assigned to undergo TSPA for presumed appendicitis at Yale-New
      Haven Hospital. The novel approach involves an innovative "puppeteer technique,"
      which uses a "pulley" in the form of an intraabdominally placed loop to the
      abdominal wall as an axle to elevate the appendix with a string. The thread is
      pulled by the surgeon extracorporeally, similar to a puppeteer moving the limbs
      of his or her puppets. RESULTS: Of the 14 patients, 13 (8 women and 5 men)
      underwent a successful TSPA. One patient was converted to a two-port
      appendectomy. The average age of the patients was 37.5 years (range, 22-59
      years), and the average body mass index (BMI) was 27.4 kg/m(2) (range, 19.4-39
      kg/m(2)). The mean operative time was 87.5 min (range, 54-128 min). No major
      complications were observed. One minor postoperative complication occurred,
      involving urinary retention, which resolved within 24 h. CONCLUSIONS: The novel
      "puppeteer technique" seems to be a safe and easily reproducible alternative to
      previous laparoscopic appendectomy techniques. It uses only one single 11-mm port
      without any additional skin incisions or transdermally traversing needles. It is
      performed entirely intracorporeally, resulting in presumably less postoperative
      pain and improved cosmesis. Randomized controlled trials are necessary to
      investigate this novel technique. The TSPA technique, the first of its kind in
      the treatment of appendicitis, minimizes the minimally invasive approach to a new
      level.

PMID- 19169750
TI  - (S)-2-acetoxy-5-undecanone, female sex pheromone of the raspberry cane midge,
      Resseliella theobaldi (Barnes).
AB  - The raspberry cane midge, Resseliella theobaldi, is a widespread pest of
      cultivated red raspberry in Europe. Pheromone-baited traps could provide a much
      needed, accurate means to monitor the pest. Volatiles collected separately from
      virgin female and male midges were analyzed by gas chromatography (GC) coupled to
      mass spectrometry (MS) to reveal four female-specific components. In analyses by
      GC coupled to electroantennographic (EAG) recording from the antennae of a male
      midge, at least three of these components elicited responses. Based on its GC
      retention indices and mass spectrum, we propose that the major component is 2
      acetoxy-5-undecanone and confirm this by synthesis of the racemic compound in
      seven steps and 63% yield from 4-pentenoic acid. The three minor components were
      each present at approximately 30% of the major component and were identified as 2
      undecanone, (S)-2-acetoxyundecane, and (S)-2-undecanol by comparison of GC
      retention times and mass spectra with those of synthetic standards. GC analyses
      of the female-produced volatiles on an enantioselective column showed that only
      one enantiomer of 2-acetoxy-5-undecanone was present, and this was found to be
      the S-enantiomer by hydrolytic kinetic resolution of an epoxide intermediate in
      the synthesis and also by enantioselective hydrolysis of the racemic acetate with
      a lipase enzyme. The two enantiomers were also separated by high-performance
      liquid chromatography on an enantioselective column for field tests. In two field
      trapping tests, (S)-2-acetoxy-5-undecanone was highly attractive to male R.
      theobaldi; the R-enantiomer was not attractive. The racemic compound was just as
      attractive as the S-enantiomer, and addition of the three minor components in
      racemic form at two different loads did not affect catches. The pheromone could
      be dispensed from both rubber septa and polyethylene vials for at least 1 month
      under field conditions, but the former was preferred as it gave more uniform
      release. 2-Acetoxy-5-undecanone belongs to a new group of pheromone structures in
      the Cecidomyiidae, most others being mono- or diesters.

PMID- 19169751
TI  - NMR metabolomics of thrips (Frankliniella occidentalis) resistance in Senecio
      hybrids.
AB  - Western flower thrips (Frankliniella occidentalis) has become a key insect pest
      of agricultural and horticultural crops worldwide. Little is known about host
      plant resistance to thrips. In this study, we investigated thrips resistance in F
      (2) hybrids of Senecio jacobaea and Senecio aquaticus. We identified thrips
      resistant hybrids applying three different bioassays. Subsequently, we compared
      the metabolomic profiles of these hybrids applying nuclear magnetic resonance
      spectroscopy (NMR). The new developments of NMR facilitate a wide range coverage
      of the metabolome. This makes NMR especially suitable if there is no a priori
      knowledge of the compounds related to herbivore resistance and allows a holistic
      approach analyzing different chemical compounds simultaneously. We show that the
      metabolomes of thrips-resistant and -susceptible hybrids differed considerably.
      Thrips-resistant hybrids contained higher amounts of the pyrrolizidine alkaloids
      (PA), jacobine, and jaconine, especially in younger leaves. Also, a flavanoid,
      kaempferol glucoside, accumulated in the resistant plants. Both PAs and
      kaempferol are known for their inhibitory effect on herbivores. In resistant and
      susceptible F (2) hybrids, young leaves showed less thrips damage than old
      leaves. Consistent with the optimal plant defense theory, young leaves contained
      increased levels of primary metabolites such as sucrose, raffinose, and
      stachyose, but also accumulated jacaranone as a secondary plant defense compound.
      Our results prove NMR as a promising tool to identify different metabolites
      involved in herbivore resistance. It constitutes a significant advance in the
      study of plant-insect relationships, providing key information on the
      implementation of herbivore resistance breeding strategies in plants.

PMID- 19169752
TI  - Pancreaticoduodenectomy and vascular resection: persistent controversy and
      current recommendations.

PMID- 19169753
TI  - Genome-wide association studies and aggressive surgery toward individualized
      prevention, and improved local control and overall survival for gastric cancer.

PMID- 19169754
TI  - Nanoneoadjuvant therapy of gastrointestinal stromal tumor (GIST).

PMID- 19169755
TI  - In reply: In favor of axillary lymph node dissection: need for a pragmatic view.

PMID- 19169756
TI  - Perioperative chemotherapy for gastric cancer: how should we measure the
      efficacy?

PMID- 19169757
TI  - Important matters to identify robust markers for metastasis and recurrence in
      solid cancer.

PMID- 19169758
TI  - Hyperthermic intraperitoneal chemotherapy after extensive cytoreductive surgery
      in patients with primary advanced epithelial ovarian cancer: interim analysis of
      a phase II study.
AB  - BACKGROUND: The objective of the current study was to evaluate the toxicities and
      treatment response of intraoperative hyperthermic intraperitoneal chemotherapy
      (HIPEC) in patients with advanced epithelial ovarian cancer. METHODS:
      Intraoperative HIPEC (cisplatin 75 mg/m(2), 41.5 degrees C, 90 min) was performed
      in 30 patients with residual tumor of <1 cm after cytoreductive surgery between
      January 2007 and February 2008. All the patients received adjuvant chemotherapy
      with combination platinum and taxane. Adverse events and responses to primary
      treatment were evaluated and scored as follows: grade I, observation; grade II,
      medical treatment; grade III, intervention; and grade IV, reoperation or
      admission to the intensive care unit. RESULTS: No deaths or grade IV morbidities
      were observed. One hundred seven adverse events were identified in 30 patients
      (grade I, 40; grade II, 46; grade III, 21). The most common adverse events
      affected the hematologic system (n = 26), followed by the gastrointestinal system
      (n = 23). Most adverse events were anemias requiring transfusion and
      nausea/vomiting requiring medication. Twenty-eight patients (93%) experienced
      complete remission, and two patients (7%) had progressive disease. CONCLUSION:
      HIPEC after extensive cytoreductive surgery for ovarian cancer is a procedure
      with acceptable morbidity that patients can tolerate. More follow-up is needed to
      determine the effect of HIPEC on survival.

PMID- 19169759
TI  - APC, MYH, and the correlation genotype-phenotype in colorectal polyposis.
AB  - BACKGROUND: Familial adenomatous polyposis (FAP) has been divided into two
      entities: classical (CFAP) and attenuated (AFAP). With the discovery of MYH
      associated polyposis (MAP) syndrome, the clinical differences have become
      unclear. The aim of our study was to investigate patients with polyposis treated
      in our institution for a correlation between genotype and phenotype. METHODS:
      Between 1978 and 2007, 515 patients were followed. Four groups were identified:
      AFAP, CFAP, MAP, and no-mutation patients. Clinical, surgical, histological, and
      genetic data of patients were collected and compared. Two ranges of mutations
      responsible for AFAP were used. RESULTS: Patient breakdown was CFAP patients (n =
      322/294), AFAP patients (n = 13/41), MYH patients (n = 17) and no-mut patients (n
      = 32). Patients not tested for APC mutation (n = 131) were excluded.
      Genotype/phenotype evaluation showed no difference in the number or location of
      polyps, age at colectomy, presence of cancer, or duodenal polyps. Major
      differences were found for MYH patients: later age at diagnosis, more cancers,
      fewer polyps, and more located in the right part of the colon. For
      phenotype/genotype correlation, patients aged more than 35 years at the time of
      colectomy and with fewer than 100 polyps had significantly more mutation found on
      MYH. CONCLUSIONS: This two-way analysis did not show any correlation that might
      help to identify a subgroup of patients with APC mutation that may be considered
      attenuated. It is more likely that the MAP syndrome is the real AFAP.

PMID- 19169761
TI  - A career in surgical oncology: not finding meaning, balance, and personal
      satisfaction.

PMID- 19169762
TI  - A tale of colostomy bag in poor: GI image.

PMID- 19169763
TI  - Midterm results of primary vs. secondary laparoscopic sleeve gastrectomy (LSG) as
      an isolated operation.
AB  - BACKGROUND: We investigated early and midterm results of laparoscopic sleeve
      gastrectomy (LSG) as an isolated primary and secondary operation after failed
      gastric banding. METHODS: Between May 2004 and October 2007, a total of 70
      patients (female 77%, mean age 43 (21-65) years, mean initial body mass index
      (BMI) 46 (35-61) kg/m(2)) were prospectively evaluated and operated by LSG. In 41
      patients, LSG was performed as a primary operation (group 1) and in 29 patients
      as a secondary procedure after failed gastric banding (group 2). The overall
      average follow-up time after LSG was 24 (12-53) months; follow-up rate 1 year
      after operation was 100%, after 2 years 98%, and after 3 years 95%. RESULTS:
      There were no intraoperative complications, no conversion with shorter operation
      time in group 1 (91 vs. 132 min, p = 0.001). Early morbidity of LSG was 5%
      (major) and 7% (minor); mortality was zero. Average excessive BMI loss after 1
      year was 65% (9-127%), after 2 years 63% (13-123%), and after 3 years 60% (9
      111%). Midterm morbidity was 13%. There was no significant difference between the
      two groups regarding early and midterm morbidity, reoperation rate for
      complications (11.4%), or insufficient weight loss (7%). CONCLUSIONS: LSG is a
      safe bariatric procedure with good weight loss in the first 3 years postop. It
      can be used as an isolated initial treatment and as a secondary treatment after
      failed gastric banding. However, in the absence of long-term results, we suggest
      LSG to be performed only in controlled trials.

PMID- 19169764
TI  - Laparoscopic seromyotomy for long stenosis after sleeve gastrectomy with or
      without duodenal switch.
AB  - BACKGROUND: Sleeve gastrectomy (SG) can be performed either as isolated (ISG), or
      with the malabsorptive procedure of duodenal switch (SG/DS). Among the
      postoperative complications, stenosis of the SG is relatively rare and only
      scarcely mentioned in literature. We report our experience in nine patients
      presenting a long stenosis, not eligible for endoscopic balloon dilation, and
      treated by laparoscopic seromyotomy after ISG or SG/DS. METHODS: From March 2006
      to January 2008, four patients after ISG (0.7%) and five patients after SG/DS
      (0.8%) were consecutively submitted to laparoscopic seromyotomy for long
      stenosis, not eligible for endoscopic balloon dilation. Dysphagia appeared after
      a mean time of 9.2 +/- 2.6 months (ISG) and of 18.6 +/- 13.2 months (SG/DS).
      Preoperative mean dysphagia frequency was 4 +/- 0 (ISG) and 4 +/- 0 (SG/DS).
      Gastroesophageal reflux disease (GERD) symptoms appeared as de novo in two
      patients of both groups. Barium swallow showed a stenosis at the upper part of
      the SG (2) and at the level of the incisura angularis (7). Gastroscopy evidenced
      a mean length of the stricture of 4.7 +/- 0.9 cm (ISG) and of 5.2 +/- 1.3 cm
      (SG/DS). The primary outcomes measure was stricture healing rate. Secondary
      outcomes measures included procedure time, peroperative, and postoperative
      complications, performance of barium swallow check, and GERD symptoms
      improvement. RESULTS: There were no conversions to open surgery and no mortality.
      There was no peroperative gastric perforation, but one patient was converted into
      Roux-en-Y gastric bypass (ISG). Mean operative time was 153.7 +/- 39.4 min (ISG)
      and 110 +/- 6.1 min (SG/DS). One gastric leak was recorded postoperatively (ISG).
      Mean hospital stay was 7.6 +/- 5.8 days (ISG) and 3.4 +/- 0.8 days (SG/DS).
      Barium swallow check after 1 month was satisfied in all patients, and they were
      able to tolerate a regular diet. After a mean follow-up of 21 +/- 5.6 months
      (ISG), the mean dysphagia score was reduced to 0.6 +/- 0.9, and after a mean
      follow-up of 17.6 +/- 10.5 months (SG/DS) to 0.8 +/- 0.8. De novo GERD symptoms
      improved in two patients of both groups. CONCLUSION: Laparoscopic seromyotomy
      after SG for long stenosis is feasible, and efficient for the treatment of
      symptomatic dysphagia. It has a beneficiary influence on de novo GERD symptoms
      improvement. There is, however, the risk of postoperative leak.

PMID- 19169765
TI  - Beta-catenin mediates soft tissue contracture in clubfoot.
AB  - The contracted tissues from clubfeet resemble tissues from other
      fibroproliferative disorders such as palmar fibromatosis. Beta-catenin-mediated
      signaling is a crucial pathway controlling the fibroproliferative response in
      many fibroproliferative disorders. To determine if beta-catenin signaling plays a
      role in clubfoot, contracted and less contracted tissues from clubfeet were
      studied using Western analysis to determine the protein level of beta-catenin.
      Primary cell cultures were established from these tissues, and they were treated
      with either lithium to increase beta-catenin or Dickkopf-1 to inhibit beta
      catenin. RNA was extracted from the cells and analyzed to determine how beta
      catenin regulates expression of Type III collagen, an extracellular matrix
      protein upregulated in contracted clubfoot tissue. There was a more than twofold
      increase in beta-catenin protein in the contracted tissues. Treatment with either
      lithium or Dickkopf-1 showed Type III collagen RNA expression positively
      correlated with the protein level of beta-catenin. These data support the concept
      that beta-catenin-mediated signaling plays an important role regulating
      contracture in clubfeet. Because pharmacologic agents are under development to
      block this signaling pathway, such drugs could be used in cases of severe
      stiffness to improve range of motion or to decrease the need for radical surgical
      approaches.

PMID- 19169766
TI  - Mood and attitude predict pain outcomes following arthroscopic knee surgery.
AB  - BACKGROUND: Decreased pain represents a clinically important outcome following
      arthroscopic knee surgery. However, little is known about preoperative mood and
      attitudinal factors and their potential relationship with pain outcomes. PURPOSE:
      This prospective, longitudinal study investigated the influence of preoperative
      depression, stress, and optimism on pain severity and interference with
      functioning, controlling for relevant demographic and clinical factors 1 year
      postoperatively. METHODS: Participants (N = 180, mean age = 48.2 years) completed
      scales assessing pain severity and interference both preoperatively and
      postoperatively. Demographics, depression, stress, optimism, and body mass index
      were assessed preoperatively. Physicians assessed extent of knee osteoarthritis
      during surgery. RESULTS: Hierarchical regression analyses controlling for
      relevant demographic and clinical variables revealed that optimism and stress
      were significant predictors of pain severity at 1 year but not pain interference.
      Extent of osteoarthritis predicted pain interference. CONCLUSIONS: These findings
      support that optimism and stress are important predictors of patient-rated pain
      severity. They do not, however, predict the extent to which pain interferes with
      daily functioning.

PMID- 19169767
TI  - Bone mineral density and its relationship with body mass index in postmenopausal
      women with type 2 diabetes mellitus in mainland China.
AB  - Bone mineral density (BMD) and its association with body mass index (BMI) are
      uncertain in postmenopausal women with type 2 diabetes mellitus (T2DM) in
      mainland China. This study was performed to assess this association including
      1,042 postmenopausal women with T2DM and 919 non-diabetic control subjects. Bone
      mineral density of the posteroanterior spine and of the left hip was measured by
      use of dual-energy X-ray absorptiometry. Diabetic participants were divided into
      three groups according to BMI, i.e. low BMI (DML < 18.5 kg/m(2)), intermediate
      BMI (DMM 18.5-24.9 kg/m(2)), and high BMI (DMH >or= 25 kg/m(2)). The BMD values
      of diabetic subjects between groups exhibited a significant gradient difference,
      with DML < DMM < DMH. On the fitting curves, where BMD in various skeletal
      regions varied with age, BMDs of DML were approximately 15% lower than those of
      DMM, and those of DMM were approximately 10% lower than those of DMH. For
      prevalence and risks of osteoporosis a gradient difference was observed among
      diabetic groups, DML > DMM approximately control > DMH. The osteoporosis risk was
      higher for the hip than for the lumbar spine, especially in DML. This study
      indicated that postmenopausal women with T2DM had higher BMD and lower
      osteoporosis risk in the lumbar spine, and that lower BMI was an indicator of
      osteoporosis in mainland China.

PMID- 19169772
TI  - [Editorial: surgical techniques in pediatric traumatology]].

PMID- 19169768
TI  - Hepatitis B virus associated focal and segmental glomerular sclerosis: report of
      two cases and review of literature.
AB  - The hepatitis B virus (HBV) is estimated to have infected about 350 million
      people worldwide, making it one of the most common human pathogens. Renal
      involvement is among its most common extra hepatic manifestations and usually
      manifests in the form of immune complex mediated glomerulopathy, such as
      membranous glomerulonephritis (MGN), membranoproliferative glomerulonephritis
      (MPGN), mesangioproliferative glomerulonephritis and immunoglobulin A (IgA)
      nephropathy. Occurrence of focal and segmental glomerular sclerosis (FSGS) with
      HBV infection is rare and only five cases have been reported earlier. We report
      two cases of hepatitis B associated FSGS. In both the cases, HBsAg was
      demonstrated in the renal tissue and both the cases showed response to treatment
      with lamivudine, thus indicating a possible causal association between the viral
      infection and occurrence of nephrotic syndrome.

PMID- 19169773
TI  - [Elastic Stable Intramedullary Nailing (ESIN) of forearm fractures].
AB  - OBJECTIVE: Fracture stabilization and restoration of bony anatomy with elastic
      stable intramedullary nailing (ESIN). INDICATIONS: Diaphyseal forearm fractures
      with displacements > 10 degrees . In cases of narrowing of the marrow cavity
      functional deficits can be encountered even in displacements < 10 degrees .
      CONTRAINDICATIONS: Distal metaphyseal fractures. Undislocated unstable fractures
      with no need for repositioning. Grade III open fractures. Greenstick fractures in
      patients < 5 years. SURGICAL TECHNIQUE: After skin incision 2 cm proximal to the
      distal radial epiphysis, the cortical bone is transfixed diagonally toward
      proximal (ascending). The ulnar bone is transfixed from proximal to distal
      (descending). For that, a small incision 2 cm distal to the olecranon apophysis
      is made. To reduce the risk of refractures in case of greenstick fractures at the
      forearm, bones should be broken completely after introduction of the wires.
      Furthermore, implant removal is recommended approximately 6-8 months
      postoperatively. POSTOPERATIVE MANAGEMENT: No additional fixation is required,
      allowing immediate functional treatment with early return to school. RESULTS:
      Operative treatment of forearm shaft fractures with ESIN was analyzed in 77
      children. Average duration of surgery was 44 min (10-140 min). After an average
      of 7 months (1-13 months), the nails were removed. Postoperative complications
      were analyzed in 74 patients (96%). In three patients (4%), a superficial pin
      site infection emerged. One child (1%) fell on his arm again and broke his distal
      radius during ESIN treatment, and one patient (1%) showed deflected nails after a
      refall on the arm 1 week after surgery. Assessment of functional outcome in 70
      patients revealed only two cases (3%) with minimal functional deficit.

PMID- 19169774
TI  - [Percutaneous closed pin fixation of supracondylar fractures of the distal
      humerus in children].
AB  - OBJECTIVE: Prevention of long-term angular and extension deformity of the elbow
      and restoration of full range of motion. INDICATIONS: Malalignment of > 20
      degrees in the sagittal plane in children > 6 years. Rotatory displacement as
      well as displacement in the frontal plane. CONTRAINDICATIONS: Severe
      cardiorespiratory diseases. SURGICAL TECHNIQUE: In most cases, a closed reduction
      is possible. Fixation of the fracture with two percutaneous Kirschner wires from
      lateral and medial; the pins cross beyond the fracture line and penetrate the
      metaphyseal cortex. POSTOPERATIVE MANAGEMENT: Elbow cast in 90 degrees flexion;
      the cast has to be split. Removal of cast and pins after 3-4 weeks. Occasionally
      physiotherapy required. RESULTS: Between October 2005 and September 2006, 77
      supracondylar fractures were treated. According to the classification of von Laer
      31 were type I (no displacement), 14 type II, nine type III, and 23 type IV (wide
      displacement). 34 of them required operative treatment due to nine type III and
      23 type IV displacements, as well as two cases with (unstable) type II. In all
      patients treated surgically, the elbow angle was successfully restored. At follow
      up after 8-14 months, 32 had regained full range of motion. In two children,
      extension/flexion was 0-10-120 degrees and 0-10-140 degrees , respectively. Two
      deficits of the ulnar nerve due to the operation as well as one deficit of the
      median nerve and the radial nerve due to the initial trauma recovered completely.
      According to the Flynn Score 32 patients had an excellent outcome; one result was
      classified as good and one as satisfactory. On the Mayo Performance Score all
      patients reached 100 of 100 points.

PMID- 19169775
TI  - [Arthroscopically assisted internal fixation of avulsion fractures of the
      anterior cruciate ligament during childhood and adolescence].
AB  - OBJECTIVE: Minimally invasive reduction and internal fixation of anterior tibial
      spine and anterior cruciate ligament (ACL) without harming knee joint cartilage
      and physis of the proximal tibia. INDICATIONS: Anterior tibial spine fractures
      type II-IV according to Meyers/McKeever. CONTRAINDICATIONS: ACL tears. Fractures
      of the tibial plateau. Fractures involving the growth plate (Aitken I-III).
      SURGICAL TECHNIQUE: 1. Diagnostic arthroscopy and drainage of the knee joint.
      Search for additional injuries (menisci, knee joint cartilage, collateral
      ligaments, posterior cruciate ligament). 2. Arthroscopy-assisted reduction of
      anterior tibial spine fragment. 3. Epiphyseal internal fixation with Kirschner
      wires or cannulated screws according to fragment size. POSTOPERATIVE MANAGEMENT:
      Full weight bearing as tolerated after wound healing (day 7 after surgery) in 20
      degrees of knee flexion (orthesis or ankle-sparing cast tutor). X-rays
      postoperatively and after 3 and 6 weeks. Passive and active physiotherapy
      (extension and flexion without weight bearing) 3-4 weeks postoperatively
      according to patient's age, weight and compliance. Weight bearing in knee flexion
      (stairs) 6-8 weeks postoperatively. RESULTS: 19 patients were treated from 2001
      to 2005 at an age of 7-14 years. All patients achieved free range of motion
      without pain or growth disturbances. Three patients developed slight joint laxity
      (anterior drawer test) which did not affect mobility, sports performance, joint
      surface or menisci on clinical evaluations conducted at least 1 year
      postoperatively. One patient had bony healing of the tibial spine in slight
      dislocation without impingement or decrease of range of motion within the knee
      joint.

PMID- 19169776
TI  - [Osteosynthesis in proximal forearm fractures in children].
AB  - OBJECTIVE: Closed reduction and fixation of displaced proximal radial neck or
      ulnar fractures with elastic stable intramedullary nailing (ESIN); prevention of
      circulatory disturbances and functional deficits following open reduction.
      INDICATIONS: Proximal radial neck fractures > 45 degrees displacement (< 10 years
      of age) or > 20 degrees (> 10 years of age); proximal extraarticular ulnar
      fractures > 10 degrees malalignment; combination injuries (Monteggia fracture,
      Monteggia-equivalent injury). CONTRAINDICATIONS: Minimally displaced or
      undisplaced fractures. SURGICAL TECHNIQUE: Radius: distal implantation of the
      nail; touching and fixation of the proximal fragment with the tip of the nail, if
      need be following digital or percutaneous partial reduction (Kirschner wire);
      definitive reduction by torsion of the nail. Ulna: distal implantation of a
      prebent nail; the prebent curve is placed opposite to the malalignment.
      POSTOPERATIVE MANAGEMENT: Functional treatment, no additive immobilization, no
      physical therapy. RESULTS: 78-87% very good and good functional results.

PMID- 19169777
TI  - [Intertrochanteric osteotomy of the proximal femur in childhood].
AB  - OBJECTIVE: Intertrochanteric osteotomy of the proximal femur in a safe way and
      following the preoperative planning to achieve sufficient stability for free
      movement and partial weight bearing. INDICATIONS: These depend on the underlying
      disease and the deformity. Partial dislocation of the femoral head in case of
      residual hip dysplasia. Loss of containment in Perthes' disease. Partial
      dislocation of the femoral head in neuromuscular disease. Rotational failures of
      the proximal femur (coxa antetorta/ retrotorta). Posttraumatic deformities.
      CONTRAINDICATIONS: In principle, none; the decision between indication and
      contraindication requires knowledge of the respective disease and deformity.
      SURGICAL TECHNIQUE: We know two different planning and surgical techniques, the
      so-called center-center technique and the calculated technique. Center-center
      technique:the guide wire is inserted parallel and in the center of the femoral
      neck in anteroposterior and axial view. The correction is determined by the
      screw/plate angle (100 degrees /110 degrees and 150 degrees , respectively).
      Planned/calculated technique:the guide wire is inserted in the preoperatively
      planned angle in relation to the chosen plate (100 degrees , 110 degrees or 150
      degrees ) using the angular aiming device for the anteroposterior view; in the
      axial view the guide wire is also placed parallel and into the center of the
      femoral neck. POSTOPERATIVE MANAGEMENT: Depending on the child's age, the
      underlying disease and the chosen implant, a hip spica cast-free treatment should
      be striven for: children < or = 5 years normally in a "buggy" or wheelchair,
      children > 5 years mobilization with crutches. RESULTS: The results depend on the
      experience, the accuracy of the planning and the performance of the osteotomy.
      Correction losses are described and reported. A faultlessly planned correction
      and an uncomplicated/good healing do not always have to be accompanied by an
      optimal functional result.

PMID- 19169778
TI  - [Surgical treatment of fractures of the distal tibia in adolescents].
AB  - OBJECTIVE: Injury to the epiphyseal cartilage during the period of growth plate
      closure in adolescence results in specific stereotyped injury patterns due to the
      change in biomechanics. According to the number of fragments, fractures of the
      distal tibia can be categorized into so-called two-plane and triplane I and II
      fractures. Since these fractures are involving the joint, the most important
      aspect for further therapy is the reconstruction of the joint surface. As the
      growth plate has already begun to close at this stage, relevant growth
      disturbances are unlikely. INDICATIONS: Fracture dislocation > 2 mm.
      CONTRAINDICATIONS: Undislocated fractures. Usual surgical and anesthetic risks.
      SURGICAL TECHNIQUE: Closed bone reduction is suitable for most minimally
      displaced fractures but in uncertain cases with advanced displacement, operative
      reduction may be necessary. The osteosynthesis can be achieved preferably by
      cannulated screws which, depending on the localization, can be placed
      intersecting the growth plate. POSTOPERATIVE MANAGEMENT: Basically, plaster
      immobilization is not necessary in case of stable osteosynthesis. Depending on
      the patient's cooperation and the fracture stability, a lower-leg cast may
      additionally be applied. Non-weight bearing for 6 weeks. RESULTS: While short
      term results are generally good, data on long-term outcome and possible
      development of arthrosis is still insufficient.

PMID- 19169779
TI  - [Elastic stable intramedullary nailing of femur fractures in children].
AB  - OBJECTIVE: Elastic stable intramedullary nailing (ESIN) is a minimally invasive
      osteosynthesis technique that allows sufficient stabilization of fractures in
      children. INDICATIONS: The stabilization of femur fractures with ESIN is
      recommended for diapyseal femur fractures in children > or = 4 years until
      closure of the growth plates. CONTRAINDICATIONS: Open fractures with significant
      injuries to the soft tissues as well as burst fractures should not be treated
      with ESIN. SURGICAL TECHNIQUE: Small incisions are made medial and lateral of the
      femur just above the distal growth plate. The cortex is perforated with an awl.
      The first ESIN is pushed via this perforation intramedullary retrograde via the
      fracture site to the proximal femur near the trochanteric region. Afterwards, the
      second nail is passed through the opposite cortex of the distal femur after
      opening it in the same way. The second nail has to be pushed parallel retrograde
      via the fracture site into the contralateral trochanteric region. The flexible
      nail design enables the surgeon to fix the fracture via a three-point
      stabilization. POSTOPERATIVE MANAGEMENT: Postoperative mobilization is allowed on
      crutches with reduced weight depending on the type of fracture. According to the
      ESIN position transverse fractures allow an early switch toward full weight
      bearing, whereas in fractures with multiple fragments, weight bearing should be
      reduced for several weeks until radiologic healing is seen. RESULTS: The
      minimally invasive method of ESIN is a well-accepted treatment option for femur
      fracture in children yielding good and excellent clinical results. It is the
      treatment of first choice for transverse and oblique femoral fractures (32-D/4.1
      und 32-D/5.1). Fractures with several fragments (32-D/5.2) as well as fractures
      of the metaphyseal region (31-M/3.1 und 33-M/3.1) may be difficult to stabilize
      with ESIN and might alternatively be treated with an external fixator.

PMID- 19169780
TI  - [Ante- and retrograde intramedullary nailing of humerus fractures].
AB  - OBJECTIVE: Safe and definitive stabilization of fully displaced, unstable
      fractures of the humerus which cannot be fixed conservatively; plaster cast:
      subcapital humerus fractures, fractures of the shaft, and supracondylar
      fractures. INDICATIONS: These depend on two major factors: first, on the
      morphology (strongly displaced transverse fractures, long oblique and spiral
      fractures, and comminuted fractures) and the stability of the fracture, and
      second, more often on socioeconomic aspects and comfort. Therefore, absolute and
      relative indications are known. CONTRAINDICATIONS: Stable and undisplaced
      fractures. SURGICAL TECHNIQUE: Follows the rules and principles of the ESIN
      technique (elastic stable intramedullary nailing). Preparation of the
      lateral/radial entry points; opening of the medullary canal with an awl or drill;
      introduction of both precontoured nails, of which one is C-shaped, and the other
      S-shaped. POSTOPERATIVE MANAGEMENT: No plaster cast or splint necessary, always
      functional postoperative treatment; exceptions are pain or anxiety of the child
      or parents (arm sling). RESULTS: In case of correct indication and operative
      technique, an optimal result is to be expected; the responsibility for possible
      failures lies always on the surgeon!

PMID- 19169781
TI  - [Surgical treatment of epiphysiolyses of the distal femur and the proximal
      tibia].
AB  - OBJECTIVE: Anatomic reduction and stabilization in case of dislocated injuries.
      INDICATIONS: Dislocated epiphysiolyses types Harris-Salter I and II of the distal
      femur and the proximal tibia. CONTRAINDICATIONS: General contraindications to
      anesthesia and surgical treatment as well as nondislocated injuries. SURGICAL
      TECHNIQUE: After initial closed anatomic reduction, the fracture is stabilized
      with crossing Kirschner wires. If closed reduction is not successful, open
      reduction via a small medial or lateral incision becomes necessary. Selected
      injuries with a big metaphyseal wedge should be stabilized with screws, which are
      inserted parallel to the physis. POSTOPERATIVE MANAGEMENT: Postoperative
      management of epiphysiolyses of the distal femur requires a pelvic leg cast for 4
      6 weeks. In epiphysiolyses of the proximal tibia, a long-leg cast is adequate.
      RESULTS: According to studies, complications after epiphysiolysis of the distal
      femur occur in 37-70%. Sound studies concerning epiphysiolysis of the proximal
      tibia do not exist.

PMID- 19169782
TI  - [Reconstruction of humeroradial joint].
AB  - OBJECTIVE: Reconstruction of the anatomic axis of the upper extremity and
      preservation or improvement of elbow function. INDICATIONS: Supracondylar axial
      deviation (cubitus varus/valgus). Limitation of range of motion. Cosmetic
      impairment. Psychological problems due to deformity. CONTRAINDICATIONS:
      Degenerative changes of the elbow joint in adolescents and adults due to
      rheumatoid/anti-inflammatory disease. SURGICAL TECHNIQUE: Three-dimensional open
      deformity correction of the distal humerus without wedge resection and
      stabilization by external fixation. POSTOPERATIVE MANAGEMENT: Early postoperative
      mobilization of the elbow. Average treatment time by external fixator 10-12
      weeks. RESULTS: Between 1998 and 2006, ten children underwent surgery for
      posttraumatic supracondylar deformity. Correction was achieved by means of three
      planar reorientation of the distal end of the humerus. An external fixator was
      used for stabilization. Preoperatively, all patients showed cosmetic or
      functional impairment. Follow-up was performed between 1 and 9 years (7.4 years)
      postoperatively. Subjective, clinical and radiologic criteria were evaluated.
      Three patients showed excellent, six good and one poor results. Two pin tract
      infections and one irritation of the ulnar nerve were observed during treatment.

PMID- 19169783
TI  - [Anterior cruciate ligament reconstruction with semitendinosus tendon in
      children].
AB  - OBJECTIVE: To present the technique of arthroscopy-assisted anterior cruciate
      ligament (ACL) reconstruction in children with complete ACL rupture. INDICATIONS:
      The indications for surgery are intraligamentous ruptures of the ACL with
      persistent signs and symptoms due to instability in spite of a minimum 6-month
      trial with conservative management and reduction of sports activities. Other
      decision-making factors for surgery include secondary injuries to the menisci or
      limitation of daily activities due to the instability produced by the ACL
      rupture. The indication for surgical intervention has to be judged individually
      and carefully in younger children. CONTRAINDICATIONS: Poor compliance on the part
      of the patient to participate in postoperative rehabilitation. Overexpectations
      regarding the surgical outcome (ability to participate in professional sports
      without limitations). Younger age of the patient (Tanner stage 2 or younger
      maturity), without trial of conservative treatment over a period of 6 months. ACL
      rupture at the bone-ligament region (tibial or femoral), partial rupture or
      lengthening of the ACL without rupture; in these instances, the instability may
      improve with growth. SURGICAL TECHNIQUE: Diagnostic arthroscopy to evaluate the
      knee joint and to identify associated or secondary injuries to the menisci and
      articular cartilage. If possible, these injuries should be addressed in the same
      surgical session. Preparation and stripping of the semitendinosus tendon using a
      tendon stripper. The technique used is transepiphyseal with extraosseous
      fixation. Depending on the thickness, the semitendinosus tendon is either tripled
      or quadrupled and prepared for transplantation. Single-canal technique. The
      diameter of the canal has to be selected depending on the size of the child's
      knee (usually between 6-8 mm). The tendon transplant is placed such that the
      canal is also filled with the tendon in the epiphyseal part (tendon transplant
      length usually 7 cm). Tibial canal entry medial to the tibial tuberosity,
      entering the joint at the level of the anterior horn of lateral meniscus in the
      intercondylar notch. Optimal positioning confirmed by an intraoperative negative
      impingement test of the guiding pin before drilling. Femoral canal entry placed
      at the 10:00-10:30 o'clock position on the right side, and 01:30-02:00 o'clock
      position on the left side. Care must be taken to avoid injury to the perichondral
      ring. In younger children (Tanner stage 3 or lower), avoidance of fixation
      material transfixing the epiphysis - femoral fixation performed using endobutton
      and tibial fixation with the Suture-disc. In older children (Tanner stage 4 or
      above) alternative fixation methods are possible (interference screw). The
      fixation of the ACL tendon transplant is such that reconstruction is in minimal
      tension in 30 degrees flexion. POSTOPERATIVE MANAGEMENT: Postoperative treatment
      regimen in the first 6 weeks after surgery depends on the extent of additive
      surgeries (menisci, chondral injuries) performed in the same sitting. In the
      absence of associated injuries, weight bearing is gradually increased with the
      aim of achieving full weight bearing at the end of the 1st postoperative week. In
      case of additional meniscal sutures, knee flexion is restricted to 60 degrees
      maximum and non-weight bearing for 4 weeks is advised. Postoperative mobilization
      is performed using an adjustable knee orthesis. Between 4-6 weeks
      postoperatively, the permitted flexion is gradually increased to a maximum of 90
      degrees and partial weight bearing is started. Full weight bearing and free
      movements with muscle training are started after 6 weeks. Avoidance of weight
      transmission on the flexed and rotated knee until 12 weeks postoperatively. Start
      with sports activities under supervision after 6 months, trial with professional
      sports activities after 9 months. RESULTS: 57 children with remaining growth
      potential around the knee underwent ACL reconstruction using the semitendinosus
      tendon at the Pediatric Orthopedic Unit, Department of Pediatric Surgery, Graz,
      Austria, between 2002-2007. 45 patients received ACL reconstruction with
      associated meniscal injuries. The described endobutton technique for fixation of
      the transplant has been performed since 2006. As the patients are under follow
      up, the long-term effects of this technique on growth around the knee are, to
      date, not known. 30 patients were operated before 2006 using the bioresorbable
      interference screw for fixation by ACL reconstruction with the semtendinosus
      tendon. All these patients were at Tanner stage 4 or older. 15 of these cases
      were evaluated after completion of growth, and all showed a good to excellent
      outcome in Tegner, Lysholm and IKDC (International Knee Documentation Committee)
      Scores without any growth disturbances.

PMID- 19169784
TI  - [Operative procedures for intraarticular distal humerus fractures in children and
      adolescents].
AB  - OBJECTIVE: Anatomic reduction and fragment fixation with Kirschner wires or screw
      osteosynthesis. Full range of motion and avoidance of growth disturbance.
      INDICATIONS: All displaced and secondary displaced fractures. CONTRAINDICATIONS:
      Screw osteosynthesis in small metaphyseal fragments; no contraindications for
      Kirschner wires. SURGICAL TECHNIQUE: After open reduction, osteosynthesis in
      adequately sized metaphyseal fragment is performed with a 4-mm cancellous lag
      screw or, alternatively, with Kirschner wire pinning. The Kirschner wires
      penetrate the opposite cortex and are shortened under skin level. To increase the
      stability, it is possible to place a lag screw or Kirschner wire through the
      epiphysis, parallel to the physis. In barely displaced fractures, closed
      reduction and percutaneous pinning are possible. POSTOPERATIVE MANAGEMENT:
      Postoperative immobilization in a long arm cast for 2-4 weeks, in stable lag
      screw osteosynthesis exercise out of a splint. If proper mobilization of the
      elbow cannot be achieved 3-4 weeks after cast removal, physiotherapy is required.
      RESULTS: Good results with full physical activity are obtained after precise
      reduction and stable fixation of intraarticular fractures of the distal humerus.
      To achieve full range of motion and avoid growth disturbance, it is necessary to
      perform a stable osteosynthesis.

PMID- 19169785
TI  - [Correction osteotomy of neglected "monteggia" lesion with an external fixator].
AB  - OBJECTIVE: Definite reduction of the dislocated radial head to prevent further
      damage and loss of function in case of a neglected radial head dislocation
      following Monteggia lesion. Three different operation methods are demonstrated.
      INDICATIONS: A correction must be striven for in any fresh injury. The indication
      has to be made according to the complaints in chronic dislocations. A correction
      is very difficult and not always successful. CONTRAINDICATIONS: In principle,
      none. SURGICAL TECHNIQUE: In principle, the surgical technique depends on the
      underlying disease and the kind of deformity, as well as on the instruments and
      implants available. There are different techniques: exclusive angulation
      osteotomy of the ulna (short interval after injury < 3 months), angulation
      osteotomy and additional lengthening of the ulna (mostly > 3 months after
      injury); an open procedure is seldom necessary and should be avoided.
      POSTOPERATIVE MANAGEMENT: Depending of the child's age, the technique used and
      the implant chosen (external fixator, plate), a cast-free treatment should be
      striven for (better function). RESULTS: The results depend on the surgeon's
      experience, the accuracy of planning, and the technique chosen. An intensive
      postoperative physiotherapy is mandatory, frequently with initial application of
      CPM (continuous passive motion). Loss of correction and residual malalignments
      are well known and not rare. They occur mostly in instances of insufficient
      stability and centralization of the radial head, respectively. There are no
      evident numbers but this is confirmed by clinical experience.

PMID- 19169786
TI  - [Editorial on the main theme: cartilage surgery].

PMID- 19169787
TI  - [Mega-OATS technique--autologous osteochondral transplantation as a salvage
      procedure for large osteochondral defects of the femoral condyle].
AB  - OBJECTIVE: Restoration or preservation of the loading tolerance of the knee
      joint. Delay of the development of degenerative arthrosis. INDICATIONS: Extensive
      osteochondral defects (traumatic, posttraumatic, osteochondrosis dissecans, focal
      osteochondronecrosis) within the weight-bearing zone of the femoral condyle.
      Comorbidities such as malalignment and ligament instabilities should be addressed
      prior to or, ideally, simultaneously with the Mega-OATS intervention.
      CONTRAINDICATIONS: Delocalized uni- and multicompartmental osteochondral lesions
      of the knee. Tricompartmental knee arthrosis. Acute and chronic arthritis or
      infection of the knee. Chondrocalcinosis. Not simultaneously corrected or
      noncorrectable malalignment or ligamentous instabilities. Patient's age > 55
      years. Postoperative continuation of activities with high loading stresses at
      high knee flexion angles, e.g. pavior, downhill ski racer. SURGICAL TECHNIQUE:
      Anteromedial or anterolateral arthrotomy. Exposure and measurement of the
      affected osteochondral area. Reaming of the defect until attainment of a vital
      bed of the defect. Measurement of the depths of the prepared defect. Removal of
      the medial posterior femoral condyle. Preparation of the cylinder of the
      transplant harvested from the removed posterior femoral condyle using a specially
      designed Mega-OATS workstation (diameter between 20 and 35 mm). Placement of the
      Mega-OATS cylinder in press-fit technique. POSTOPERATIVE MANAGEMENT: Initial
      continuous passive motion therapy, active range of motion 90 degrees -0 degrees 
      0 degrees , and unloading for 6 weeks postoperatively using crutches, followed by
      progressive weight bearing with 20 kg per week until full weight bearing. Free
      active range of motion as tolerated from 7th week. Four-point hard-frame knee
      orthosis for 6 weeks. Concomitant intensive muscle and proprioceptive training
      from 3rd to 6th month. Specific sports rehabilitation program starting 7th month.
      RESULTS: The initial 17 and 16 patients following Mega-OATS procedure due to a
      large osteochondral defect (average size 6 cm2, range 4-9 cm2) of the femoral
      condyle were clinically examined including an image-guided evaluation protocol at
      an average follow-up of 12 and 55 months, respectively. In the Lysholm Score,
      there was a significant increase from 62 +/- 4 points (mean +/- SEM [standard
      error of the mean]) preoperatively to 85 +/- 7 points at 12 months and 81 +/- 4
      points at 55 months postoperatively. In nine patients with varus malalignment, a
      simultaneous high tibial osteotomy was performed. However, a significant
      difference in the Lysholm Score between the subgroup with and without
      simultaneous high tibial osteotomy could not be found. In more than 90% of the
      patients, a high subjective satisfaction rate was noted. Randomized magnetic
      resonance images revealed a good viability of the Mega-OATS graft as well as an
      intact posterior horn of the ipsilateral meniscus.

PMID- 19169788
TI  - [Matrix-augmented autologous chondrocyte implantation in the knee--arthroscopic
      technique].
AB  - OBJECTIVE: Arthroscopic implantation of resorbable, three-dimensional scaffolds
      for the treatment of full-thickness cartilage defects. INDICATIONS: Full
      thickness cartilage defect mainly in the knee joint. CONTRAINDICATIONS: Advanced
      osteoarthritis, rheumatoid arthritis, avascular osteonecrosis. SURGICAL
      TECHNIQUE: Debridement of the defect, assessment of the defect size, sizing of
      the implant, implantation into the joint, and fixation. POSTOPERATIVE MANAGEMENT:
      Continuous active and passive motion, pain-adapted weight bearing with crutches,
      possibly toe-touch loading depending on size and localization of the defect.
      RESULTS: After 2 years, good and excellent results in 80% of the cases with
      femoral cartilage defects on the modified Cincinnati Knee Rating Scale. Inferior
      results for defects of the patella and tibia.

PMID- 19169789
TI  - [Matrix-associated autologous chondrocyte transplantation (MACT). Minimally
      invasive technique in the knee].
AB  - OBJECTIVE: Repair of localized cartilage defects in the knee. INDICATIONS:
      Localized partial or full-thickness cartilage defects in the knee or
      osteochondral lesions (osteochondritis dissecans [OD]). CONTRAINDICATIONS:
      Generalized cartilage defects, osteoarthritis, bacterial and rheumatoid
      arthritis, uncorrected axis deformities, ligament instability, patella
      instability, meniscectomy. SURGICAL TECHNIQUE: Two-step procedure. 1. Diagnostic
      arthroscopy and cartilage biopsy for cell cultivation. 2. Minimalized arthrotomy.
      Defect debridement. Autologous cancellous bone grafting in OD. Glueing of the
      cell-loaded scaffold into the defect. POSTOPERATIVE MANAGEMENT: Early functional
      rehabilitation with knee orthosis. Partial weight bearing (20 kg) for 6 weeks.
      RESULTS: 50 patients (24 female, 26 male, age 14-44 years, mean 30.3 years) with
      58 focal cartilage defects (III-IV degrees) of the knee in the medial (n = 32) or
      lateral condyle (n = 5), patella (n = 14) and/or trochlea (n = 7) underwent
      matrix-associated autologous chondrocyte implantation (MACI). The mean follow-up
      was 24 months (21-29 months). The mean defect size was 4.1 cm2(1.6-6.1 cm2). The
      Lysholm Score improved from 57.3 to 87.4 points, the DGKKT (German Society of
      Autologous Cartilage and Bone Cell Transplantation) Score from 55.3 to 85.5
      points. Pain on a visual analog scale (VAS) diminished from 5.5 to 2.1, while
      subjective function enhanced from 4.5 to 7.6. All scores were significant (p <
      0.01; t-test). In eleven patients (twelve defects), a second-look arthroscopy
      revealed a mostly fibrocartilaginous regenerative tissue in 41.7% (5/12) and a
      mixed fibrous/hyaline regenerative tissue in 33.4% (4/12). 54% (27/50) of the
      patients estimated their result as excellent, 28% (14/50) as good, 16% as fair,
      and 2% (1/50) as poor.

PMID- 19169791
TI  - [Open operative treatment of acute glenoid fractures following anterior and
      posterior shoulder dislocation].
AB  - OBJECTIVE: Acute osseous fractures of the glenoid (avulsion of the labrum
      ligament-capsule complex including anterior-inferior osseous glenoid lesions as
      well as fractures of the fossa glenoidalis) need to be regarded as absolute
      indication for surgery due to the incidence of recurrent dislocations and danger
      of secondary progressive glenoid defects. As a basic principle of surgery, the
      bone-labrum-ligament-capsule complex has to be refixated and the osseous geometry
      reconstructed anatomically. INDICATIONS: Anterior dislocations: all traumatic
      dislocations in association with a fossa glenoidalis or glenoid rim defect.
      Posterior dislocations: all unstable situations with osseous glenoid defects
      persisting after reposition. CONTRAINDICATIONS: Brachial plexus injury. Poor
      glenoid bone stock. SURGICAL TECHNIQUE: Anterior glenoid defect: exposition of
      the glenoid through a deltopectoral approach. Fragment refixation depending on
      fragment size with suture anchor devices or cannulated screws. Posterior glenoid
      defect: exposition of the glenoid through a modified Brodsky approach from
      posterolateral. Exposure of the posterior capsule between infraspinatus and teres
      minor muscles, medial casulotomy. Reposition and refixation of the osseous
      fragment analogous to anterior lesions. In fractures with glenoid neck or
      scapular body affection additional fixation and support through plate
      osteosynthesis at the margo lateralis scapulae. In case of persisting instability
      reconstruction of the glenoid defect with an autologous graft with or without
      endoprosthetic glenoid resurfacing is optional. POSTOPERATIVE MANAGEMENT: To
      preserve reconstructed anatomy, a Gilchrist sling is required for 4-6 weeks after
      anterior reconstructions. For postoperative treatment of posterior defects, a
      thorax abduction splint is recommended for 6 weeks. Reduced ROM (range of motion)
      exercise is provided under physiotherapeutic guidance according to individual
      pathology. RESULTS: Clinical results following open surgery of osseous glenoid
      lesions are generally very good. In the own patients, an average Constant Score
      of 88, a Rowe Score of 89, and a Simple Shoulder Test according to Matsen of 85%
      could be achieved.

PMID- 19169790
TI  - [The dorsal flag flap for skin coverage of finger and thumb-tip injuries].
AB  - OBJECTIVE: Immediate two-step coverage of dorsal finger and thumb-tip soft-tissue
      defects with a dorsal flag flap, which can bridge over two fingers if necessary.
      INDICATIONS: Soft-tissue defects on the dorsal aspect of fingers between the
      metacarpophalangeal and the distal interphalangeal joint as well as on the tip of
      the thumb. CONTRAINDICATIONS: Large defects, complex hand trauma, need of a
      sensible thumb tip, infections, noncompliance. SURGICAL TECHNIQUE: Marking of the
      flap at the middle phalanx and its flagpole pedicle, containing the dorsal
      digital artery. The breadth should reach to the middle of the finger and the
      proximal pole should not cross the middle of the proximal phalanx. With
      tourniquet dissection of the flap above the peritendineum with respect of the
      dorsal digital artery and subcutaneous veins in the pedicle. Opening of the
      tourniquet, in the case of flap perfusion transposition of the flap into the
      defect. Coverage of the donor site with skin graft. POSTOPERATIVE MANAGEMENT:
      Palmar cast splinting in intrinsic-plus position for 1 week, followed by
      physiotherapy. Pedicle separation after 3 weeks. Continuation of physiotherapy
      and scar care. RESULTS: In 2006, ten patients were operated on, three of them for
      reconstruction of the thumb tip. All patients showed a survival of the flap and a
      good wound healing without complications. One patient developed a flexion
      contracture at the donor finger due to noncompliance following immobilization.
      The functional and aesthetic results were satisfactory in all patients, the
      average DASH Score ("Disabilities of the Arm, Shoulder and Hand") was 16.4,
      mainly due to the residuals of the overall injury.

PMID- 19169792
TI  - [Minimally invasive total hip arthroplasty via direct anterior approach].
AB  - OBJECTIVE: Minimally invasive total hip arthroplasty via direct anterior approach
      aims at reducing soft-tissue damage, diminishing blood loss and postoperative
      pain, shortening stay in hospital, accelerating rehabilitation, and keeping scars
      small. INDICATIONS: The technique is suitable for primary and secondary
      osteoarthritis as well as fractures of the femoral neck. Complex distortions of
      the proximal femur should be exempted. CONTRAINDICATIONS: Complex malalignment of
      the proximal femur. SURGICAL TECHNIQUE: The femoral neck is exposed in the
      interval between tensor fasciae latae, glutei medius and minimus muscles
      laterally, and sartorius and rectus femoris muscles medially. After osteotomy of
      the neck and extraction of the head the acetabulum is reamed to prepare for cup
      prosthesis. Following peritrochanteric capsulotomy the externally rotated,
      adducted and elevated femor is broached. Cemented and cementless implants may be
      used. POSTOPERATIVE MANAGEMENT: The patients are allowed to walk full weight
      bearing beginning on the 1st postoperative day. As soon as they are able to
      safely master the transfers and stairs, they are discharged. RESULTS: The method
      is a safe procedure that allows correct placement of acetabular and femoral
      components. It may be performed in a reasonable time, the blood loss is little.
      The procedure preserves the muscles and leads to small, cosmetically pleasing
      scars. Patients usually do not suffer from pronounced pain, rehabilitation is
      accelerated. They therefore agree in an short postoperative stay in hospital.

PMID- 19169793
TI  - [The distally based sural neurocutaneous island flap for coverage of soft-tissue
      defects on the distal lower leg, ankle and heel].
AB  - OBJECTIVE: Stable coverage of soft-tissue defects in the critical regions of the
      distal lower leg, ankle and heel by avoidance of a microsurgically transplanted
      free flap. INDICATIONS: Soft-tissue defects < or = 10 cm in diameter--either by
      trauma or complications (skin necrosis, infection)--on the distal lower leg,
      ankle or heel with exposed osseous, tendinous or articular structures including
      high-risk patients (diabetes mellitus type 1/2 and/or arterial vascular disease
      including stage IIb, not capable of improvement). CONTRAINDICATIONS: Relative:
      diameter of defect > 10 cm. Absolute: critical ischemia (arterial vascular
      disease stages III and IV). SURGICAL TECHNIQUE: Outlining of the sural island
      flap directly over the small saphenous vein. Fasciocutaneous flap elevation
      proceeding in a proximal-distal direction. Lipofascial dissection of the 3 cm
      wide and up to 15 cm long neurovascular pedicle after longitudinal skin incision
      starting at the distal border of the island flap and running distally. Point of
      pedicle rotation 5 cm above the tip of the fibula. Flap passage into the defect
      through subcutaneous tunnel or after incision of the soft tissue between defect
      and donor site. Skin closure over region of pedicle dissection, meshed skin
      grafting of donor site. POSTOPERATIVE MANAGEMENT: Immobilization of the lower leg
      in a well-padded cast over a period of about 10 days. RESULTS: In a retrospective
      study, eleven out of twelve patients (including six high-risk patients) with a
      distally based sural neurocutaneous flap were examined on average 3.7 years
      postoperatively. The mean age was 54.9 years (28-80 years). A stable coverage of
      the defect was achieved in all twelve patients. In ten of twelve sural flaps the
      defect site was closed by primary wound healing, additional procedures were
      necessary in two cases (meshed skin grafting of flap border, excision of skin
      necrosis). All patients examined were satisfied with the result of the primary
      operative target, the stable coverage of the defect. Stated disadvantages were
      loss of sensation in the area of sural nerve function (four times), aesthetic
      impairment (twice), and pain resulting from sural nerve neuroma above donor site
      (once).

PMID- 19169794
TI  - [Osteotomies in varus malalignment of the ankle].
AB  - OBJECTIVE: Joint-preserving osteotomies in patients with symptomatic varus
      malalignment of the ankle. Osseous procedures together with soft-tissue
      rebalancing are performed at the level of the distal tibia/fibula or calcaneus.
      Realignment of the joint line will subsequently reduce intraarticular forces at
      the ankle and thereby slow down the degenerative process. INDICATIONS: Varus
      malalignment of the ankle with remaining cartilage in the tibiotalar joint.
      CONTRAINDICATIONS: Severe neurovascular deficiencies. Severe instability of the
      hindfoot. Severe cartilage lesions of the entire ankle (grade 3-4 according to
      Outerbridge). SURGICAL TECHNIQUE: Varus deformities of the distal tibia: medial
      opening-wedge osteotomy or lateral closing-wedge osteotomy. The lateral closing
      procedure requires an osteotomy of the fibula. Varus deformity of the hindfoot:
      valgization by lateral closing- wedge osteotomy of the calcaneus and lateral
      shift of the calcaneal tuberosity, i.e., Z-shaped osteotomy. Additional
      procedures at the first metatarsal and softtissue procedures must be considered
      in all these patients. POSTOPERATIVE MANAGEMENT: Immobilization in a non-weight
      bearing cast for 6-8 weeks. Thereafter, increase in weight bearing as tolerated.
      Physiotherapy for muscular strengthening and restoration of gait pattern.
      RESULTS: Twelve patients with an osteotomy of the distal tibia presented with a
      significant reduction of pain on a visual analog scale (p = 0.0001) and an
      increased range of motion of 33 degrees (5-55 degrees ) preoperatively compared
      to 39 degrees (25-50 degrees ) postoperatively. Radiologic assessment also
      revealed an improvement of preexisting arthritic signs. All 18 patients treated
      with a Z-shaped calcaneal osteotomy reported pain relief with osseous
      consolidation after 6 months.

PMID- 19169795
TI  - [Split transfer of the extensor hallucis longus tendon in flexible hallux varus
      deformity].
AB  - OBJECTIVE: Realignment of a flexible hallux varus deformity through split
      transfer of the extensor hallucis longus tendon. INDICATIONS: Flexible hallux
      varus deformity without any osseous deformity in patients with painful calluses,
      worsening of the varus position, or imminent lesser toe deformities.
      CONTRAINDICATIONS: Contract hallux varus deformity, bony malalignment, painful
      arthritic first metatarsophalangeal joint, neuropathy, infection. SURGICAL
      TECHNIQUE: Medial release with VY-lengthening of the capsule. Tenotomy of the
      abductor hallucis tendon. Lateral reefing of the metatarsophalangeal joint
      capsule. Transfer of the split extensor hallucis longus tendon beneath the
      intermetatarsal ligament to the lateral aspect of the phalanx. POSTOPERATIVE
      MANAGEMENT: Dressing with the great toe in an appropriate position. Immediate
      weight bearing in a forefoot relief orthosis for 4 weeks. Comfortable shoes for
      the next 2 weeks. Physiotherapy (muscular strengthening, standing on tiptoes,
      aquajogging) after 6 weeks. RESULTS: Twelve patients were followed up clinically
      and radiologically after a mean of 18 months. Four patients complained of pain
      during weight bearing (barefoot walking and wearing soft-soled shoes). Another
      seven patients presented with a limited range of motion in the first
      metatarsophalangeal joint. Overall, the range of motion has decreased
      significantly (p < 0.05). In five patients, an average varus position of 14
      degrees was found on plain radiographs. Clinically, this malalignment was obvious
      in only two patients. All patients presented with sufficient ground contact of
      the great toe. As arthritic changes have not been detected radiologically, the
      limited range of motion in the first metatarsophalangeal joints has to be
      attributed to the tenodesis effect of the transferred tendon slip.

PMID- 19169796
TI  - EMT, the cytoskeleton, and cancer cell invasion.
AB  - The metastatic process, i.e. the dissemination of cancer cells throughout the
      body to seed secondary tumors at distant sites, requires cancer cells to leave
      the primary tumor and to acquire migratory and invasive capabilities. In a
      process of epithelial-mesenchymal transition (EMT), besides changing their
      adhesive repertoire, cancer cells employ developmental processes to gain
      migratory and invasive properties that involve a dramatic reorganization of the
      actin cytoskeleton and the concomitant formation of membrane protrusions required
      for invasive growth. The molecular processes underlying such cellular changes are
      still only poorly understood, and the various migratory organelles, including
      lamellipodia, filopodia, invadopodia and podosomes, still require a better
      functional and molecular characterization. Notably, direct experimental evidence
      linking the formation of migratory membrane protrusions and the process of EMT
      and tumor metastasis is still lacking. In this review, we have summarized recent
      novel insights into the molecular processes and players underlying EMT on one
      side and the formation of invasive membrane protrusions on the other side.

PMID- 19169797
TI  - Signal transduction by focal adhesion kinase in cancer.
AB  - Cellular interactions with extracellular matrix play essential roles in tumor
      initiation, progression and metastasis. Focal adhesion kinase (FAK) is a
      cytoplasmic tyrosine kinase identified as a key mediator of signaling by
      integrins, a major family of cell surface receptors for extracellular matrix, as
      well as other receptors in both normal and cancer cells. FAK is activated by
      integrins through disruption of an auto-inhibitory intra-molecular interaction
      between its kinase domain and the amino terminal FERM domain. The activated FAK
      forms a binary complex with Src family kinases which can phosphorylate other
      substrates and trigger multiple intracellular signaling pathways to regulate
      various cellular functions. Subcellular localization of FAK in focal adhesions is
      essential for FAK signaling, which is another distinguishing feature of the
      kinase. Integrin-FAK signaling has been shown to activate a number of signaling
      pathways through phosphorylation and protein-protein interactions to promote
      tumorigenesis. FAK also plays a prominent role in tumor progression and
      metastasis through its regulation of both cancer cells and their
      microenvironments including cancer cell migration, invasion, epithelial to
      mesenchymal transition, and angiogenesis. More recently, a role for FAK in tumor
      initiation and progression has been demonstrated directly using xenograft as well
      as conditional knockout mouse models. In agreement with these experimental data,
      overexpression and activation of FAK have been found in a variety of human
      cancers. A number of small molecule inhibitors for FAK have been developed and in
      various phases of testing for cancer treatments. Overall, the intensive research
      on FAK signaling in cancer have yielded a wealth of information on this pivotal
      kinase and these and future studies are leading to potentially novel therapies
      for cancer.

PMID- 19169798
TI  - The rise and fall of syphilis in Renaissance Europe.
AB  - The rapid changes that syphilis underwent after the first major outbreak that
      occurred in Naples in the mid-1490s are believed to constitute the first well
      documented example of a human disease. The new plague was of exceptional
      virulence, highly contagious and causing severe ulceration at the site of
      infection. According to medical and other historical sources, the 'genius
      epidemics' changed some years after this onset, and a slower-progressing form of
      syphilis seems to have replaced the initial severe form, as do many virulent
      epidemic infectious diseases that appear in devastating forms in a previously
      uninfected population. But what exactly were the features of the disease at the
      moment of its appearance in Europe at the end of the fifteenth century? How many
      years did it take for the early, virulent form to be replaced and become endemic?
      What was the pace of these changes through the decades following the onset of the
      epidemic? In this essay, I review these issues through an analysis of a large
      number of chronologically-ordered primary historical sources.

PMID- 19169799
TI  - Cultural cognition and public policy: the case of outpatient commitment laws.
AB  - What explains controversy over outpatient commitment laws (OCLs), which authorize
      courts to order persons with mental illness to accept outpatient treatment? We
      hypothesized that attitudes toward OCLs reflect "cultural cognition" (DiMaggio,
      P. Annl Rev Sociol 23:263-287, 1997), which motivates individuals to conform
      their beliefs about policy-relevant facts to their cultural values. In a study
      involving a diverse sample of Americans (N = 1,496), we found that individuals
      who are hierarchical and communitarian tend to support OCLs, while those who are
      egalitarian and individualistic tend to oppose them. These relationships,
      moreover, fit the cultural cognition hypothesis: that is, rather than directly
      influencing OCL support, cultural values, mediated by affect, shaped individuals'
      perceptions of how effectively OCLs promote public health and safety. We discuss
      the implications for informed public deliberation over OCLs.

PMID- 19169800
TI  - Is the prevalence of specific types of congenital heart defects different for non
      Hispanic white, non-Hispanic black and Hispanic infants?
AB  - BACKGROUND: Our purpose was to determine the prevalence of specific types of CHD
      among non-Hispanic (NH)-Black, NH-White, and Hispanic infants. METHODS: We
      conducted a retrospective cohort study with 9,352 singleton infants diagnosed
      with conotruncal, right or left obstructive or septal CHDs from the Florida Birth
      Defects Registry, born 1998-2003 to resident NH-White, NH-Black, and Hispanic
      women aged 15-49. Defect-specific prevalence rates, prevalence ratios and P
      values were calculated for each type of CHD and by number of defects for each
      racial/ethnic group. RESULTS: Compared to NH-Whites, NH-Blacks had higher rates
      of pulmonary valve atresia/stenosis but lower frequency of aortic valve
      atresia/stenosis and ventricular septal defect. Hispanics had lower rates of
      aortic valve atresia/stenosis and atrioventricular septal defects than NH-Whites.
      CONCLUSIONS: Although few racial/ethnic differences in prevalence are present
      among infants with major CHD, observed differences are clinically meaningful.
      However, the underlying etiologies for the observed differences remain unknown.

PMID- 19169801
TI  - The influence of sodium and potassium dynamics on excitability, seizures, and the
      stability of persistent states: I. Single neuron dynamics.
AB  - In these companion papers, we study how the interrelated dynamics of sodium and
      potassium affect the excitability of neurons, the occurrence of seizures, and the
      stability of persistent states of activity. In this first paper, we construct a
      mathematical model consisting of a single conductance-based neuron together with
      intra- and extracellular ion concentration dynamics. We formulate a reduction of
      this model that permits a detailed bifurcation analysis, and show that the
      reduced model is a reasonable approximation of the full model. We find that
      competition between intrinsic neuronal currents, sodium-potassium pumps, glia,
      and diffusion can produce very slow and large-amplitude oscillations in ion
      concentrations similar to what is seen physiologically in seizures. Using the
      reduced model, we identify the dynamical mechanisms that give rise to these
      phenomena. These models reveal several experimentally testable predictions. Our
      work emphasizes the critical role of ion concentration homeostasis in the proper
      functioning of neurons, and points to important fundamental processes that may
      underlie pathological states such as epilepsy.

PMID- 19169802
TI  - Slow and fast pulses in 1-D cultures of excitatory neurons.
AB  - We analyze the characteristics of front propagation in activity of 1-D neuronal
      cultures by numerical simulations, using only excitatory dynamics. Experimental
      results in 1-D cultures of hippocampal neurons from rats have shown the
      spontaneous generation of a slow, low amplitude pulse that precedes a high
      amplitude, fast pulse that propagates through all the system. Notably, this
      transition appears both with and without the presence of functioning inhibitory
      synapses. In accordance with previous work, we demonstrate that purely excitatory
      integrate and fire neurons with depression in the synapses suffice to produce
      fast and uniform pulses but cannot explain the appearance of slow, weak pulses.
      We propose to explain the slow pulses by increasing the complexity of the neuron
      model in a purely excitatory network with connectivity as close to the
      experiments as possible. This approach allows us to show that spike frequency
      adaptation is a fundamental ingredient for the initiation process of the pulse.
      The introduction of a slow variable that mimics the presence of the slow K(+)
      channels in the soma and produces spike frequency adaptation increases strongly
      the persistence of the transient activity before the emergence of the fast pulse
      up to temporal and spatial scales comparable with the experiments. Finally, we
      demonstrate that proper levels of additive white noisy currents generate such
      pulses spontaneously, fully reproducing the experimental results.

PMID- 19169803
TI  - Concealment of sexual orientation.
AB  - Sex-atypical behaviors may be used to identify a person as homosexual. To shield
      themselves from prejudice, homosexual people may attempt to conceal these
      behaviors. It is not clear how effectively they can do so. In Study 1, we asked
      homosexual participants to conceal their sex-atypical behaviors while talking
      about the weather. Raters watched videos of the participants and judged the
      likelihood that each participant was homosexual. Homosexual participants were
      able to partially conceal signs of their orientation, but they remained
      distinguishable from heterosexual participants. In Study 2, we tested the ability
      to conceal signs of one's sexual orientation in a more demanding situation: a
      mock job interview. In this scenario, homosexual men were even less effective at
      concealing their orientation. Higher cognitive demands in this new situation may
      have interfered with their ability to conceal.

PMID- 19169805
TI  - Genetic variation in Chinese pine (Pinus tabulaeformis), a woody species endemic
      to China.
AB  - Random amplified polymorphic DNA markers were used to investigate genetic
      variation of the Chinese pine (Pinus tabulaeformis Carr.), a species endemic to
      China and the most widely distributed pine species in North China. The results
      revealed that P. tabulaeformis populations had a relatively high level of genetic
      diversity (H(t) = 0.3268), distributed mainly within (79.2%) rather than among
      (20.8%) populations. The populations of Lingkong Mountain and Wuling Mountain had
      a higher level of diversity (0.2687) than the other four populations (0.2537). No
      statistically significant relationships were found between genetic diversity and
      climatic factors by correlation analysis and between genetic distance and
      geographic distance by the Mantel test. These results suggest that the
      partitioning of genetic diversity in each population might have been influenced
      not only by water and temperature conditions but also by other factors such as
      human activities and the Holocene postglacial history of these populations.

PMID- 19169804
TI  - Non-pharmacological treatments for insomnia.
AB  - Insomnia is a common disorder effecting millions of people worldwide. Currently
      most individuals suffering from insomnia take medications to help them sleep.
      However, there are a variety of behavioral treatments, which have been shown to
      be effective in empirical studies that offer many advantages over medications. In
      addition, behavioral treatments have been shown to be more effective long-term
      than medication. This paper reviews the principles and practice of these
      behavioral treatments. At the end of the paper there is also a brief discussion
      of circadian rhythm disorders that can mimic insomnia.

PMID- 19169806
TI  - Genetic variability, differentiation, and founder effect in golden jackals (Canis
      aureus) from Serbia as revealed by mitochondrial DNA and nuclear microsatellite
      loci.
AB  - We analyzed 121 golden jackals (Canis aureus) from six sample sites in Serbia
      with regard to genetic variability and differentiation as revealed by
      mitochondrial control region sequences and eight nuclear microsatellite loci.
      There was no variation at all in the mtDNA sequences, and nuclear variability was
      very low (average observed and expected heterozygosity of 0.29 and 0.34,
      respectively). This is in line with the considerable recent range expansion of
      this species in the Balkans and indicates a strong founder effect in the recently
      established Serbian population. We did not find evidence of differentiation
      between the northeastern jackals and those from the plain of Srem or those in
      between. F-statistics and Bayesian Structure analyses, however, were indicative
      of a low degree of overall differentiation in the Serbian population. A vagrant
      Austrian jackal that was also analyzed was genetically indistinguishable from its
      Serbian conspecifics.

PMID- 19169807
TI  - Characterization and SNP identification of part of the goat melanophilin gene.
AB  - The melanophilin (MLPH) gene has been characterized as the candidate gene for
      dilute coat color in some species, but little is known about it in the goat. In
      this study, part of the genomic DNA sequence (19,289 bp) containing the whole
      coding region of the MLPH gene from goat, as well as from sheep, was determined.
      We found 16 exons and 15 introns; the coding region was 1767 bp distributed in 15
      exons (2-16). In sheep, the length of part of the genomic DNA sequence was 16,988
      bp, with 16 exons and 15 introns, and the coding region was 1833 bp, distributed
      in 15 exons (2-16). Dozens of SNPs as well as some noticeable motifs in the goat
      MLPH gene were found during the process of sequencing and polymorphism screening.
      Based on the SSR Tool, three simple sequence repeat motifs were detected in the
      goat and sheep DNA sequences. Compared with cattle, we found insertions of 4
      amino acids in goats and 26 amino acids in sheep.

PMID- 19169809
TI  - Analysis of expressed sequence tags in porcine uterus tissue.
AB  - Two non-normalized cDNA libraries of uteri from Danish Landrace and Chinese
      Erhualian pigs were constructed, and 13,756 expressed sequence tags (ESTs) were
      randomly sequenced. The ESTs were clustered by Phrap software, and 6,139 distinct
      tentative consensus sequences were produced, including 2,730 contigs and 3,409
      singlets. Using Blast tools, these 6,139 candidate genes were compared to the nr
      and nt databases; 5,210 of them were assigned putative functions, whereas 929
      potentially represent new genes. Highly expressed genes appear to be associated
      with basic energy metabolism, transferase activity, localization, cellular
      physiological process, protein binding, and nucleic acid binding.
      Antileukoproteinase was the most highly expressed gene, corresponding to
      endometrial differentiation and conceptus or fetal development.

PMID- 19169808
TI  - Utilization of the porcine system to study lymphotoxin-beta regulation in
      intestinal lymphoid tissue.
AB  - Lymphotoxin-beta (LT-beta) has been suggested to be a regulator of secondary
      lymphoid structure development. In the present study, we isolated porcine LT-beta
      (poLT-beta) from adult swine spleens. The open reading frame encoded a predicted
      246-amino acid polypeptide exhibiting higher similarity to the human than the
      mouse LT-beta protein. Expression of LT-beta mRNA in various swine tissues was
      analyzed by real-time PCR, and it was found to be higher in the ileal Peyer's
      patches (Pps) of adults than in newborns. In addition, ligand stimulation of toll
      like receptors 2, 4, and 9, which are activated by bacterial components,
      increased LT-beta expression only in neonatal ileal Pps. These results suggest
      that colonization by commensal bacteria may affect the maturation of neonatal
      ileal Pps by the induction of LT-beta via toll-like receptors. LT-beta may
      therefore be useful for studying the development of the intestinal immune system
      at parturition in both swine and humans.

PMID- 19169810
TI  - Symptoms of depression and anxiety in adolescents with sickle cell disease: the
      role of intrapersonal characteristics and stress processing variables.
AB  - Sickle cell disease (SCD) complications place patients at risk for poor
      psychosocial adaptation, including depression and anxiety symptoms. This study
      aimed to test a mediator model based on the Risk and Resistance model to explore
      the role of intrapersonal characteristics and stress processing variables in
      psychosocial functioning. Participants were 44 adolescents with SCD, 15 healthy
      siblings, and 43 primary caregivers, recruited from an East Coast comprehensive
      sickle cell center. The participants completed paper and pencil measures of
      resilience factors (attributional style, hope, coping) and internalizing symptoms
      (depression, anxiety). Internalizing symptoms among adolescents with SCD and
      healthy siblings did not differ and were within non-clinical ranges. Self-esteem
      of adolescents with SCD was correlated with less depression and anxiety and sense
      of inadequacy was associated with poorer functioning. There were no findings to
      support the role of coping in psychosocial adjustment. Although the mediation
      hypothesis was not supported, findings highlighted the resilience of this sample
      of adolescents with SCD. Determining how these resilience factors protect
      adolescents with SCD may aid in the development of psychosocial interventions. In
      particular, interventions should focus on improving intrapersonal skills and
      coping with stress and investigate ways to tailor these interventions to African
      American populations.

PMID- 19169811
TI  - A comprehensive evaluation of outcomes for inflammatory breast cancer.
AB  - OBJECTIVE: Inflammatory breast cancer (IBC) remains the breast malignancy with
      the worst prognosis. We sought to determine the effects of race, socioeconomic
      status and treatment on outcomes for women with IBC. Study design The Florida
      cancer registry, inpatient and ambulatory data were queried for patients
      diagnosed from 1998 to 2002. RESULTS: A total of 935 patients with IBC were
      identified (1.5% of all breast cancers). Overall, 83.1% were Caucasian, 13.9%
      African American (AA), and 15.7% Hispanic. The mean age of diagnosis was 57 years
      old. AA patients presented at a younger age, with higher tumor grade, and were
      less likely to undergo surgical therapy than their Caucasian counterparts. Median
      survival time (MST) for the entire cohort was 32 months, while MST for AA
      patients was 20 months. Patients who received chemotherapy before surgery,
      surgery without chemotherapy, and surgery before chemotherapy demonstrated an
      independent, significantly improved outcome in comparison to patients who
      underwent chemotherapy without surgical extirpation. The administration of
      radiation therapy did not demonstrate an improvement in survival. By multivariate
      analysis, AA race (HR = 2.19) and failure to provide surgery (HR = 2.3) were
      independent predictors of worse prognosis. No effect of poverty or ethnicity on
      outcome was observed. CONCLUSIONS: IBC carries a poor prognosis for all patients
      with significantly worse outcomes for AA women. Multimodality therapy provided
      the best survival rates.

PMID- 19169812
TI  - A high-resolution integrated analysis of genetic and expression profiles of
      breast cancer cell lines.
AB  - Tumour cell lines derived from breast cancer patients constitute one of the
      cornerstones of breast cancer research. To characterise breast cancer cell lines
      at the genetic level, we have developed a full tiling path bacterial artificial
      chromosome (BAC) array collection for comparative genomic hybridisation (aCGH).
      This aCGH BAC collection covers 98% of the entire human genome at a resolution of
      40-60 kbp. We have used this platform alongside an in-house produced 17 K cDNA
      microarray set to characterise the genetic and transcriptomic profiles of 24
      breast cancer cell lines, as well as cell types derived from non-diseased breast.
      We demonstrate that breast cancer cell lines have genomic and transcriptomic
      features that recapitulate those of primary breast cancers and can be reliably
      subclassified into basal-like and luminal subgroups. By overlaying aCGH and
      transcriptomic data, we have identified 753 genes whose expression correlate with
      copy number; this list comprised numerous oncogenes recurrently amplified and
      overexpressed in breast cancer (e.g., HER2, MYC, CCND1 and AURKA). Finally, we
      demonstrate that although breast cancer cell lines have genomic features usually
      found in grade III breast cancers (i.e., gains of 1q, 8q and 20q), basal-like and
      luminal cell lines are characterised by distinct genomic aberrations.

PMID- 19169813
TI  - HU210-induced downregulation in cannabinoid CB1 receptor binding strongly
      correlates with body weight loss in the adult rat.
AB  - In vitro autoradiography was used to examine changes in cannabinoid CB1 receptors
      (targeted with [(3)H] CP55,940) in rats treated with the potent cannabinoid
      agonist HU210. Animals were administered with HU210 (25, 50, 100 microg/kg) for 4
      or 14 days or received a single 100 microg/kg injection of HU210 and sacrificed
      24 h later. The acute dose resulted in a decrease in binding in the caudate
      putamen and hippocampus. A dose dependent, region-specific reduction (P < 0.0001)
      in [(3)H] CP55,940 binding was seen in all brain regions examined after 4 and 14
      days treatment. A decrease in body weight was recorded during the first 4 days of
      treatment but after this animals began to gain weight. Correlations (0.865 < r <
      0.659, P < 0.0001) between body weight on day four and CB1 receptor binding were
      found in all brain regions examined suggesting that downregulation of CB1
      receptors may contribute to the induction of tolerance to body weight loss
      induced by HU210.

PMID- 19169814
TI  - Coriaria lactone increased the intracellular level of calcium through the voltage
      gated calcium channels in rat hippocampal neurons.
AB  - To investigate the effects of Coriaria Lactone (CL), an epileptogenic substance,
      on intracellular levels of calcium ([Ca(2+)](i)) and physiological properties of
      voltage-gated calcium channels (VGCCs). Ratiometric calcium imaging using Fura
      Red and whole-cell voltage patch-clamp technique were explored on freshly
      isolated rat hippocampal neurons exposed to CL. Coriaria Lactone increased
      [Ca(2+)](i) from 118 +/- 21 to 440 +/- 35 nM; VGCCs and calcium influx through
      NMDA receptor served as the main routes of entry. Coriaria Lactone could enhance
      both Low voltage activated (LVA) and High voltage activated calcium currents in a
      concentration-dependent way, and its effect on LVA current was more potent (about
      60%). The increased calcium currents were accompanied by the shift of voltage
      dependent steady-state inactivation to more positive potentials. These effects of
      CL, especially its impact on LVA current, could activate different calcium
      dependent signaling pathways, and influence cellular excitable properties as
      well, which might play an important role in CL's epileptogenic process.

PMID- 19169815
TI  - Role of glutamate and GABA transporters in development of pentylenetetrazol
      kindling.
AB  - Kindling is a form of epileptogenesis that can be induced with pentylenetetrazol
      (PTZ). We undertook this study to evaluate the contribution of glutamate and GABA
      transporters to the process of PTZ kindling. Rats were injected i.p. three times
      per week with PTZ (40 mg/kg) until they were fully kindled. In rats who achieved
      full kindling, measurement of hippocampal glutamate and GABA transporters within
      24 h by western blot showed that GLAST, GLT-1, and EAAC1 were elevated
      significantly. However, fully kindled rats at 30 days after their last seizure
      had no change in either glutamate or GABA transporters proteins. These sequential
      observations suggest that glutamate transporters may contribute to the occurrence
      of seizures, but were not associated with maintenance of epileptogenesis. During
      this experiment, we collected data from animals that had kindled easily and
      animals who were resistant to kindling. Easily-kindled rats reached full kindling
      with less than five injections of PTZ. Kindling resistant animals failed to
      achieve full kindling even after administration of 12 consecutive injections of
      PTZ. Levels of EAAC1 and GAT-1 in easily-kindled rats were decreased by 30% when
      compared to kindling resistant animals at 30 days after the last PTZ injection.
      Since decreased EAAC1 and GAT-1 would diminish GABA function, less quantity of
      these proteins would appear to be associated with the convulsive threshold at the
      beginning of kindling development. We wonder if glutamate and GABA transporters
      might be operant in a convulsion threshold set factor or as a pace factor for
      kindling.

PMID- 19169816
TI  - Protective effect of granulocyte colony-stimulating factor on intracerebral
      hemorrhage in rat.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a member of the cytokine family
      of growth factors that can protect the neurons from focal cerebral ischemia
      induced injuries. The intracerebral hemorrhage (ICH) has been widely observed in
      the clinic; however, the protective effect of G-CSF on ICH is still elusive. We
      found in the present study that the intraperitoneal injection of G-CSF for 5 days
      could improve the ICH-induced neuronal behavioral impairment measured by limb
      placement assay. We also observed that injection of G-CSF could increase the
      number of stem cells in the specific zone of the hemorrhagic areas, demonstrated
      by the enhanced expression of nestin. Additionally, G-CSF could also promote the
      mobilization of circulating hemopoietic stem cells (HSCs) to the damaged brain
      areas and activate the astrocytes. Our results reveal that G-CSF is also
      protective for the ICH with the mechanisms involving proliferation of neural stem
      cells, the migration of HSCs and the activation of astrocytes.

PMID- 19169817
TI  - Comparison and optimisation of transfection of human dental follicle cells, a
      novel source of stem cells, with different chemical methods and electro-poration.
AB  - INTRODUCTION: Human dental follicle cells (HDFCs) derived from human impacted
      third molars (wisdom teeth) have been shown to be a significant source of adult
      stem cells. Generation of mesenchymal stem cell-like cells from dental follicles
      causes minimal surgical stress. In vitro and in vivo reports showed that HDFCs
      can be utilized in gene and cell therapy applications which make them an
      attractive alternative source for different gene-cell therapy applications.
      However, there are currently no systematic comparative studies on transfection
      potential of HDFC cells using different chemical and electro-poration techniques.
      METHODS: Stem cells from impacted third tooth molars were isolated, and analyzed
      for expression of surface markers. Transfection efficiencies of four commercially
      available transfection reagents (Transfast, Escort V, Superfect and FuGene HD)
      and electro-poration on isolated stem cells were compared. RESULTS: Isolated
      HDFCs were stained positive for CD105, CD90, CD73, CD166, and negative for CD34,
      CD45, and CD133. Among the chemical transfection reagents used in this study,
      FuGene HD was the most efficient in transfecting HDFCs, even in the presence of
      10% serum. CONCLUSION: Electro-poration of HDFCs yield relatively high
      transfection rates and cell viability when compared to chemical transfection
      techniques. Our observations might be useful for developing gene and cell therapy
      applications using dental follicle stem cells.

PMID- 19169820
TI  - New clinical method for distinguishing D-IBS from other gastrointestinal
      conditions causing diarrhea: the LA/IBS diagnostic strategy.
AB  - Modern methods of diagnosing diarrhea-predominant irritable bowel syndrome (D
      IBS) require a "diagnosis of exclusion" approach. In this study we aim to test
      the diagnostic ability of using the fluctuation of frequency and consistency of
      bowel patterns in IBS to discriminate it from other causes of diarrhea. Eligible
      subjects were asked to complete a questionnaire on the changes in form and
      frequency of bowel habits by time. The primary endpoint was to evaluate the
      diagnostic effectiveness of having irregularly irregular bowel function and form
      as more characteristic of IBS versus non-IBS causes. Patients were prospectively
      recruited from a tertiary care GI clinic. Subjects had to have diarrhea as their
      primary complaint. In the case of IBS, D-IBS subjects were recruited. Subjects
      with celiac disease, Crohn's and ulcerative colitis were recruited for comparison
      and were categorically called "non-IBS." Non-IBS subjects could not have a recent
      history of blood in stool or a history of bowel surgery, fistulae or narcotic
      use. Sixty-two IBS and 37 non-IBS subjects were recruited. Among the 62 IBS
      subjects, 49 (79%) stated that their bowel habits varied in form and frequency on
      a daily basis compared to 35% in non-IBS subjects (OR = 8.9, CI = 3.5-22.5, P <
      0.00001). When subjects were compared by the number of different stool forms they
      had witnessed in the prior week, IBS subjects noted 3.58 +/- 0.19 types and non
      IBS reported 2.35 +/- 0.16 (P < 0.00001). Using > or = 3 stool forms per week as
      a method of discriminating IBS from non-IBS, 50 out of 62 subjects with IBS (81%)
      reported this greater number of forms compared to 15 out of 37 (41%) non-IBS
      subjects (sensitivity = 0.81; specificity = 0.60). The use of this simple tool
      that identifies an irregularly irregular bowel form and function is successful in
      separating D-IBS from non-IBS subjects.

PMID- 19169818
TI  - Effect of hyperoxia on serine phosphorylation of apoptotic proteins in
      mitochondrial membranes of the cerebral cortex of newborn piglets.
AB  - Previous studies have shown that hyperoxia results in cerebral cortical neuronal
      apoptosis. Studies have also shown that phosphorylation of anti-apoptotic
      proteins Bcl-2 and Bcl-xl results in loss of their anti-apoptotic potential
      leading to alteration in mitochondrial membrane permeability and the release of
      apoptogenic proteins in the neuronal cell of the newborn piglets. The present
      study tests the hypothesis that cerebral hyperoxia will result in increased
      serine phosphorylation of apoptotic proteins Bcl-2, Bcl-xl, Bax, and Bad in the
      mitochondrial membranes of the cerebral cortex of newborn piglets. Twelve newborn
      piglets were divided into normoxic (Nx, n = 6) exposed to an FiO(2) of 0.21 for 1
      h and hyperoxic (Hyx, n = 6) exposed to FiO(2) of 1.0 for 1 h. In the Hyx group,
      PaO(2) was maintained above 400 mmHg while the Nx group was kept at 80-100 mmHg.
      Cerebral cortical tissue was harvested and mitochondrial fractions were isolated.
      Mitochondrial membrane proteins were separated using 12% SDS-PAGE, and probed
      with anti-serine phosphorylated Bcl-2, Bcl-xl, Bax, and Bad antibodies. Protein
      bands were detected, analyzed by imaging densitometry and density expressed as
      absorbance (OD x mm(2)). Phosphorylated Bcl-2 (p-Bcl-2) protein density (OD x
      mm(2)) was 81.81 +/- 9.24 in Nx and 158.34 +/- 10.66 in Hyx (P < 0.05).
      Phosphorylated Bcl-xl (p-Bcl-xl) protein density was 52.98 +/- 3.59 in Nx and
      99.62 +/- 18.22 in Hyx (P < 0.05). Phosphorylated Bax (p-Bax) protein was 161.13
      +/- 6.27 in Nx and 174.21 +/- 15.95 in Hyx (P = NS). Phosphorylated Bad (p-Bad)
      protein was 166.24 +/- 9.47 in Nx 155.38 +/- 12.32 in Hyx (P = NS). The data show
      that there is a significant increase in serine phosphorylation of Bcl-2 and Bcl
      xl proteins while phosphorylation of Bad and Bax proteins were not altered during
      hyperoxia in the mitochondrial fraction of the cerebral cortex of newborn
      piglets. We conclude that hyperoxia results in differential post-translational
      modification of anti-apoptotic proteins Bcl-2 and Bcl-xl as compared to pro
      apoptotic proteins Bax and Bad in mitochondria. We speculate that phosphorylation
      of Bcl-2 and Bcl-xl will result in loss of their anti-apoptotic potential by
      preventing their dimerization with Bax leading to activation of the caspase
      cascade of neuronal death.

PMID- 19169821
TI  - Simultaneous quantification of perfusion and permeability in the prostate using
      dynamic contrast-enhanced magnetic resonance imaging with an inversion-prepared
      dual-contrast sequence.
AB  - The aim of the present study was to quantify both perfusion and extravasation in
      the prostate to discriminate tumor from healthy tissue, which might be achieved
      by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using a
      nonspecific low-molecular-weight contrast medium (CM). To determine extravasation
      as well as tissue perfusion an inversion-prepared dual-contrast sequence
      employing a parallel acquisition technique (PAT) was designed for interleaved
      acquisition of T(1)-weighted images for extravasation measurement and T(2)*
      weighted images for determination of the highly concentrated bolus with a
      sufficiently high temporal and spatial resolution at an acceptable signal-to
      noise ratio. Thirteen patients with proven prostate cancer were examined with the
      sequence using a combined body-array prostate coil. Before pharmacokinetic
      evaluation the images were intensity-corrected and, if required, motion
      corrected. The pharmacokinetic model used to calculate perfusion, permeability,
      blood volume, interstitial volume, transit time, and vessel size index included
      two compartments and a correction of delay and dispersion of the arterial input
      function. The information provided by the dual-contrast sequence allowed
      application of a more elaborate model for evaluation and enabled quantification
      of all parameters. Peripheral prostate tumors were found to differ from
      peripheral healthy prostate tissue in perfusion (1.38 mL/(min cm(3)) vs. 0.23
      mL/(min cm(3)), p=0.004), mean transit time (2.88 vs. 4.88 s, p=0.039), and blood
      volume (1.9 vs. 0.7%, p=0.019). A inversion-prepared dual-contrast sequence
      acquiring T(1)- and T*(2)-weighted images with sufficient temporal resolution and
      signal-to-noise ratio was successfully applied in patients with prostate cancer
      to quantify all pharmacokinetic parameters of inflow and extravasation of a low
      molecular-weight inert tracer.

PMID- 19169822
TI  - Design of multifunctional nanomedical systems.
AB  - Multifunctional nanoparticles hold great promise for drug/gene delivery and
      simultaneous diagnostics and therapeutics ("theragnostics") including use of core
      materials that provide in vivo imaging and opportunities for externally modulated
      therapeutic interventions. Multilayered nanoparticles can act as nanomedical
      systems with on-board molecular programming done through the chemistry of highly
      specialized layers to accomplish complex and potentially decision-making tasks.
      The targeting process itself is a multi-step process consisting of initial cell
      recognition through cell surface receptors, cell entry through the membrane in a
      manner to prevent undesired alterations of the nanomedical system, re-targeting
      to the appropriate sub-region of the cell where the therapeutic package can be
      localized, and potentially control of that therapeutic process through feedback
      systems using molecular biosensors. This paper describes a bionanoengineering
      design process in which sophisticated nanomedical platform systems can be
      designed for diagnosis and treatment of disease. The feasibility of most of these
      subsystems has been demonstrated, but the full integration of these interacting
      sub-components remains a challenge for the field. Specific examples of sub
      components developed for specific applications are described.

PMID- 19169823
TI  - Hallmarks for senescence in carcinogenesis: novel signaling players.
AB  - Cellular senescence is a potent anti-cancer mechanism controlled by tumor
      suppressor genes, particularly p53 and pRb, which is characterized by the
      irreversible loss of proliferation. Senescence induced by DNA damage, oncogenic
      stimulation, or excessive mitogenic input, serves as a barrier that counteracts
      cancer progression. Emerging evidence in cellular and in in vivo models revealed
      the involvement of additional signaling players in senescence, including PML,
      CK2, Bcl-2, PI3K effectors such as Rheb, Rho small GTPases, and cytokines. Recent
      studies have also implicated protein kinase C (PKC) isozymes as modulators of
      senescence phenotypes and showed that phorbol esters, widely used PKC activators,
      can induce senescence in a number of cancer cells. These novel findings suggest a
      complex array of cross-talks between senescence pathways and may have significant
      implications in cancer therapy.

PMID- 19169824
TI  - Nuclear translocation kinetics of NF-kappaB in macrophages challenged with
      pathogens in a microfluidic platform.
AB  - We have developed a microfluidic platform for real-time imaging of host-pathogen
      interactions and cellular signaling events. Host cells are immobilized in a
      controlled environment for optical interrogation of the kinetics and
      stochasticity of immune response to pathogenic challenges. Here, we have
      quantitatively measured activation of the toll-like receptor 4 (TLR4) pathway in
      RAW264.7 murine macrophage-like cells. This was achieved by measuring the
      cytoplasm-to-nucleus translocation kinetics of a green fluorescent protein fusion
      construct to the NF-kappaB transcription factor subunit RelA (GFP-RelA).
      Translocation kinetics in response to live bacteria and purified
      lipopolysaccharide (LPS) challenges were measured, and this work presents the
      first demonstration of live imaging of host cell infection on a microfluidic
      platform with quantitative analysis of an early (<0.5 h from infection) immune
      signaling event. Our data show that a 1,000x increase in the LPS dose led to a
      ~10x increase in a host cell activation metric we developed in order to describe
      NF-kappaB translocation kinetics. Using this metric, live bacteria challenges
      were assigned an equivalent LPS dose as a first step towards comparing NF-kappaB
      translocation kinetics between TLR4-only pathway signaling (activated by LPS) and
      multiple pathway signaling (activated by whole bacteria). The device also
      contains a unique architecture for capturing and fluidically isolating single
      host cells for the purpose of differentiating between primary and secondary
      immune signaling.

PMID- 19169825
TI  - Application of an asymmetric helical tube reactor for fast identification of gene
      transcripts of pathogenic viruses by micro flow-through PCR.
AB  - We have established a fast PCR-based micro flow-through process consisting of a
      helical constructed tube reactor. By this approach we can detect transcripts of
      measles and human papilloma virus (HPV) by continuous flow allowing for reverse
      transcription (RT) and amplification of cDNA. The micro reaction system consisted
      of two columnar reactors for thermostating the different reaction zones of the RT
      process and the amplification. The PCR reactor was built by asymmetric heating
      sections thus realizing different residence times and optimal conditions for
      denaturation, annealing and elongation. The system concept is based on low
      electrical power consumption (50-120 W) and is suited for portable diagnostic
      applications. The samples were applied in form of micro fluidic segments with
      single volumes between 65 and 130 nL injected into an inert carrier liquid inside
      a Teflon FEP tube with an inner diameter of 0.5 mm. Optimal amplification for
      template lengths of 292 bp (lambda-DNA), 127 bp (measles virus) and 95 bp (HPV)
      was achieved by maximal cycle times of 75 s.

PMID- 19169826
TI  - An implantable MEMS drug delivery device for rapid delivery in ambulatory
      emergency care.
AB  - We introduce the first implantable drug delivery system based on MEMS (Micro
      Electro-Mechanical-Systems) technology specifically designed as a platform for
      treatment in ambulatory emergency care. The device is named IRD(3) (implantable
      rapid drug delivery device) and allows rapid delivery of drugs. Vasopressin was
      used as a model drug for in vitro tests as it is a commonly used drug for cardiac
      resuscitation. Experimental results reveal that the IRD(3) provides an effective
      method for rapid delivery without significant drug degradation. Several medical
      uses and delivery modalities for IRD(3) are proposed.

PMID- 19169827
TI  - Towards a single-chip, implantable RFID system: is a single-cell radio possible?
AB  - We present an overview of progress towards single-chip RFID solutions. To date
      heterogeneous integration has been appropriate for non-biological systems.
      However, for in-vivo sensors and even drug delivery systems, a small form factor
      is required. We discuss fundamental limits on the size of the form factor, the
      effect of the antenna, and propose a unified single-chip RFID solution
      appropriate for a broad range of biomedical in-vivo device applications, both
      current and future. Fundamental issues regarding the possibility of single cell
      RF radios to interface with biological function are discussed.

PMID- 19169828
TI  - Nanobiology for the pharmacology of cellular ion channels.
AB  - Writing this editorial is especially pleasing. First, it provides us an
      opportunity to introduce new directives to the field of Neuroimmune Pharmacology
      and to explain why the field of nanomedicine is likely an important part of its
      future growth and development. Second, it is an opportunity to showcase research
      in this area currently operative in Russia that may not be readily accessible to
      the readership. Third, it is a platform to better explain why the Journal
      Editorial leadership was enthusiastic about the science and its relationship to
      the Society on NeuroImmune Pharmacology strategic goals. All are brought to bear
      in this issue of the Journal of Neuroimmune Pharmacology. The issue includes
      articles presented at a recent joint US-Russian workshop entitled, "Health in the
      21st Century: Nanomedicine and Self-Organization of Biological Systems" held at
      M.V. Lomonosov Moscow State University (MSU), Moscow, Russia, December 10-11,
      2007. The conjoint meeting was organized through the Departments of Biology,
      Chemistry, and Physics, MSU and by the Center for Drug Delivery and Nanomedicine
      and Department of Pharmacology and Experimental Neuroscience, University of
      Nebraska Medical Center (Omaha, NE). The speakers included established
      internationally regarded scientists from these institutions as well as graduate
      students and faculties at MSU. In addition to selected papers by workshop
      contributors, we have included several papers closely aligned to the theme of
      nanomedicine and nanopharmacology of the central nervous system in order to
      provide a biological anchor for this research. We understand that such works are
      new to many but hope that its organization and interdisciplinary approaches will
      appeal to this audience. All together, it is our hope that, by gathering basic
      and clinical scientists with the common interest of using nanotechnology in the
      delivery of therapeutic agents with a focus on nanopharmacology and complex
      supramolecular biological assembly, the papers included will provide a platform
      for thought, discussion, and future translational research.

PMID- 19169829
TI  - The LIVESTRONG Survivorship Center of Excellence Network.
AB  - INTRODUCTION: The LIVESTRONG Survivorship Center of Excellence Network consists
      of eight National Cancer Institute-designated Comprehensive Cancer Centers funded
      by the LAF between 2004 and 2008. The Network was created to accelerate the pace
      of progress in addressing the needs of the growing survivor community. METHODS:
      This paper will briefly describe some of the salient issues surrounding the care
      of cancer survivors, and examine models of survivorship care that are being
      developed in individual Centers of Excellence (COE) as well as in the overall
      Network. RESULTS AND CONCLUSIONS: As the recommendations and policies for optimal
      survivorship care have to be feasible and relevant in the community setting, each
      COE is partnered with up to three community affiliates. Through these
      partnerships, the community affiliates develop survivorship initiatives at their
      institutions with support and guidance from their primary COE.

PMID- 19169830
TI  - Treatment of early stage thymic tumors: surgery and radiation therapy.
AB  - Tumors of the thymus are an uncommon entity, constituting 30% and 15% of anterior
      mediastinal masses in adults and children, respectively. The majority of these
      tumors are thymomas, with thymic carcinomas less common, and thymic carcinoids
      exceedingly rare. Recognition of the distinct clinicopathologic behavior of
      various thymic neoplasms is crucial to providing optimal treatment. Evidence
      guiding the treatment of early stage thymic tumors is limited secondary to the
      low incidence and resulting lack of randomized data. Proper management requires a
      careful analysis of the available literature with particular attention paid to
      limitations of the existing studies. This article provides a discussion of the
      presentation, evaluation, diagnosis, surgical techniques, and treatment outcomes
      relevant to early stage thymomas, thymic carcinomas, and thymic carcinoid tumors.
      The role of radiation therapy in the management of early stage thymic tumors
      remains controversial and is discussed in detail.

PMID- 19169831
TI  - Chronic lymphocytic leukemia: new concepts and emerging therapies.
AB  - OPINION STATEMENT: Remarkable progress in elucidating the biology of chronic
      lymphocytic leukemia (CLL) has been made over the last two decades. Improved
      understanding of CLL has lead to new prognostic tools and therapeutic options,
      and holds promise for eventually finding a cure for this disease. Challenges lie
      in incorporating the various treatment modalities, including chemotherapy,
      monoclonal antibodies, immunotherapeutic strategies and novel small molecules,
      into a comprehensive treatment strategy guided by the biological complexity of
      CLL.

PMID- 19169832
TI  - Comments on controversial tick (Acari: Ixodida) species names and species
      described or resurrected from 2003 to 2008.
AB  - There are numerous discrepancies in recent published lists of the ticks of the
      world. Here we review the controversial names, presenting evidence for or against
      their validity and excluding some altogether. We also address spelling errors and
      present a list of 17 species described or resurrected during the years 2003-2008.
      We consider the following 35 tick species names to be invalid: Argas fischeri
      Audouin, 1826, Ornithodoros boliviensis Kohls and Clifford, 1964, Ornithodoros
      steini (Schulze, 1935), Amblyomma acutangulatum Neumann, 1899, Amblyomma arianae
      Keirans and Garris, 1986, Amblyomma bibroni (Gervais, 1842), Amblyomma
      colasbelcouri (Santos Dias, 1958), Amblyomma concolor Neumann, 1899, Amblyomma
      cooperi Nuttall and Warburton, 1908, Amblyomma curruca Schulze, 1936, Amblyomma
      cyprium Neumann, 1899, Amblyomma decorosum (Koch, 1867), Amblyomma nocens
      Robinson, 1912, Amblyomma perpunctatum (Packard, 1869), Amblyomma striatum Koch,
      1844, Amblyomma superbum Santos Dias, 1953, Amblyomma testudinis (Conil, 1877),
      Amblyomma trinitatis Turk, 1948, Dermacentor confractus (Schulze 1933),
      Dermacentor daghestanicus Olenev, 1928, Haemaphysalis himalaya Hoogstraal, 1966,
      Haemaphysalis vietnamensis Hoogstraal and Wilson, 1966, Hyalomma detritum
      Schulze, 1919, Ixodes apteridis Maskell, 1897, Ixodes donarthuri Santos Dias,
      1980, Ixodes kempi Nuttall, 1913, Ixodes neotomae Cooley, 1944, Ixodes
      rangtangensis Teng, 1973, Ixodes robertsi Camicas, Hervy, Adam and Morel, 1998,
      Ixodes serrafreirei Amorim, Gazetta, Bossi and Linhares, 2003, Ixodes tertiarius
      Scudder, 1885, Ixodes uruguayensis Kohls and Clifford, 1967, Ixodes zealandicus
      Dumbleton, 1961, Ixodes zumpti Arthur, 1960 and Rhipicephalus camelopardalis
      Walker and Wiley, 1959. We consider the following 40 names valid: Argas delicatus
      Neumann, 1910, Argas vulgaris Filippova, 1961, Ornithodoros aragaoi Fonseca,
      1960, Ornithodoros dugesi Mazzoti, 1943, Ornithodoros knoxjonesi Jones and
      Clifford, 1972, Ornithodoros marocanus Velu, 1919, Ornithodoros nattereri
      Warburton, 1927, Amblyomma beaurepairei Vogelsang and Santos Dias, 1953,
      Amblyomma crassipes (Neumann, 1901), Amblyomma echidnae Roberts, 1953, Amblyomma
      fuscum Neumann, 1907, Amblyomma orlovi (Kolonin, 1995), Amblyomma parkeri Fonseca
      and Aragao, 1952, Amblyomma pseudoconcolor Aragao, 1908, Bothriocroton oudemansi
      (Neumann, 1910), Bothriocroton tachyglossi (Roberts, 1953), Dermacentor abaensis
      Teng, 1963, Dermacentor confragus (Schulze 1933), Dermacentor ushakovae Filippova
      and Panova, 1987, Haemaphysalis anomaloceraea Teng, 1984, Haemaphysalis
      filippovae Bolotin, 1979, Haemaphysalis pavlovskyi Pospelova-Shtrom, 1935,
      Hyalomma excavatum Koch, 1844, Hyalomma isaaci Sharif, 1928, Hyalomma rufipes
      Koch, 1844, Hyalomma turanicum Pomerantzev, 1946, Ixodes arabukiensis Arthur,
      1959, Ixodes boliviensis Neumann, 1904, Ixodes columnae Takada and Fujita, 1992,
      Ixodes maslovi Emel'yanova and Kozlovskaya, 1967, Ixodes sachalinensis Filippova,
      1971, Ixodes siamensis Kitaoka and Suzuki, 1983, Ixodes sigelos Keirans, Clifford
      and Corwin, 1976, Ixodes succineus Weidner, 1964, Rhipicephalus aurantiacus
      Neumann, 1907, Rhipicephalus cliffordi Morel, 1965, Rhipicephalus pilans Schulze,
      1935, Rhipicephalus pseudolongus Santos Dias, 1953, Rhipicephalus serranoi Santos
      Dias, 1950 and Rhipicephalus tetracornus Kitaoka and Suzuki, 1983.

PMID- 19169833
TI  - Acaricidal effects of Corymbia citriodora oil containing para-menthane-3,8-diol
      against nymphs of Ixodes ricinus (Acari: Ixodidae).
AB  - The toxicity of para-menthane-3,8-diol (PMD), the main arthropod-repellent
      compound in the oil of the lemon eucalyptus, Corymbia citriodora, was evaluated
      against nymphs of Ixodes ricinus using five methods (A-E) of a contact toxicity
      bioassay. Mortality rates were estimated by recording numbers of dead nymphs at
      30 min intervals during the first 5 h after the start of exposure and at longer
      intervals thereafter. The mortality rate increased with increasing concentration
      of PMD and duration of exposure with a distinct effect after 3.5 h. From the
      results obtained by methods A, C and E, the LC(50) range was 0.035-0.037 mg
      PMD/cm(2) and the LC(95) range was 0.095-0.097 mg PMD/cm(2) at 4 h of exposure;
      the LT(50) range was 2.1-2.8 h and the LT(95) range was 3.9-4.2 h at 0.1 mg
      PMD/cm(2). To determine the duration of toxic activity of PMD, different
      concentrations (0.002, 0.01, 0.1 mg PMD/cm(2)) were tested and mortality was
      recorded at each concentration after 1 h; thereafter new ticks were tested. This
      test revealed that the lethal activity of PMD remained for 24 h but appeared
      absent after 48 h. The overall results show that PMD is toxic to nymphs of I.
      ricinus and may be useful for tick control.

PMID- 19169834
TI  - Continuous measurement of multiple inert and respiratory gas exchange in an
      anaesthetic breathing system by continuous indirect calorimetry.
AB  - A method was tested which permits continuous monitoring from a breathing system
      of the rate of uptake of multiple gas species, such as occurs in patients during
      inhalational anaesthesia. The method is an indirect calorimetry technique which
      uses fresh gas rotameters for control, regulation and measurement of the gas
      flows into the system, with continuous sampling of mixed exhaust gas, and
      frequent automated recalibration to maintain accuracy. Its accuracy was tested in
      16 patients undergoing pre-cardiopulmonary bypass coronary artery surgery,
      breathing mixtures of oxygen/air and sevoflurane with/without nitrous oxide, by
      comparison with the reverse Fick method. Overall mean bias [95% confidence
      interval (CI)] of rate of uptake was 17.9 [7.3 to 28.5] ml min(-1) for oxygen,
      0.04 [-0.42 to 0.50] ml min(-1) for sevoflurane, 10.9 [-16.1 to 37.8] for CO(2),
      and 8.8 [-14.8 to 32.4] ml min(-1) for nitrous oxide where present. The method
      proved to be accurate and precise, and allows continuous monitoring of exchange
      of multiple gases using standard gas analysis devices.

PMID- 19169836
TI  - Selection of MSW landfill site for Konya, Turkey using GIS and multi-criteria
      evaluation.
AB  - Landfill is a common solution for the final disposal of municipal solid waste
      (MSW) in Turkey. Landfill siting is an extremely difficult task to accomplish
      because the site selection process depends on different factors and regulations.
      To ensure that an appropriate site is chosen, a systematic process should be
      developed and followed. Unsuccessful landfill siting is typically the result of
      strong public opposition. In this study, candidate sites for an appropriate
      landfill area in Cumra County of Konya City are determined by using the
      integration of geographic information systems (GIS) and multi-criteria evaluation
      (MCE). ArcGIS 9.0 software and its extensions were used as the GIS tool since it
      is able to perform suitability analysis using MCE analysis. To identify
      appropriate landfill areas in the Cumra district, eight input map layers
      including proximity to municipal and local wells and irrigational canals,
      distance from transportation routes and rails, distance from archaeological
      sites, distance from urban areas, land use/land cover, and land slope are used in
      constraint mapping. A final map was generated which identifies regions showing
      suitability for the location of the landfill site. According to the map, 6.8% of
      the study area is most suitable, 15.7% is suitable, 10.4% is moderately suitable,
      25.8% is poorly suitable, and 41.3% is unsuitable. At the end of the analyses,
      three candidate sites are determined. The selection of the final MSW landfill
      site, however, requires further field research.

PMID- 19169835
TI  - Specificity improvement for network distributed physiologic alarms based on a
      simple deterministic reactive intelligent agent in the critical care environment.
AB  - Automated physiologic alarms are available in most commercial physiologic
      monitors. However, due to the variability of data coming from the physiologic
      sensors describing the state of patients, false positive alarms frequently occur.
      Each alarm requires review and documentation, which consumes clinicians' time,
      may reduce patient safety through 'alert fatigue' and makes automated physician
      paging infeasible. To address these issues a computerized architecture based on
      simple reactive intelligent agent technology has been developed and implemented
      in a live critical care unit to facilitate the investigation of deterministic
      algorithms for the improvement of the sensitivity and specificity of physiologic
      alarms. The initial proposed algorithm uses a combination of median filters and
      production rules to make decisions about what alarms to generate. The alarms are
      used to classify the state of patients and alerts can be easily viewed and
      distributed using standard network, SQL database and Internet technologies. To
      evaluate the proposed algorithm, a 28 day study was conducted in the University
      of Michigan Medical Center's 14 bed Cardiothoracic Intensive Care Unit. Alarms
      generated by patient monitors, the intelligent agent and alerts documented on
      patient flow sheets were compared. Significant improvements in the specificity of
      the physiologic alarms based on systolic and mean blood pressure was found on
      average to be 99% and 88% respectively. Even through significant improvements
      were noted based on this algorithm much work still needs to be done to ensure the
      sensitivity of alarms and methods to handle spurious sensor data due to patient
      or sensor movement and other influences.

PMID- 19169837
TI  - Composition of ovarian fluid in endangered Caspian brown trout, Salmo trutta
      caspius, and its effects on spermatozoa motility and fertilizing ability compared
      to freshwater and a saline medium.
AB  - In this study, ovarian fluid composition and its effects on the motility and
      fertilizing ability of sperm were studied in endangered Caspian brown trout,
      Salmo trutta caspius, and were compared with a saline activation medium (125 mM
      NaCl, 30 mM Glycine, 20 mM Tris-HCl, pH = 9.0) and freshwater as the control. The
      ovarian fluid was composed of sodium 164.4 +/- 4.4 mM l(-1), potassium 1.8 +/-
      0.1 mM l(-1), calcium 0.6 +/- 0.1 mM l(-1), magnesium 0.4 +/- 0.02 mM l(-1),
      chloride 127.4 +/- 5.9 mM l(-1), total protein 389.5 +/- 89.6 mg 100 ml(-1),
      cholesterol 9.3 +/- 1.2 mg dl(-1), and glucose 3.3 +/- 0.2 mM l(-1). The
      percentage of motile spermatozoa and the duration of sperm motility were
      significantly higher in ovarian fluid (62 +/- 3%, 74.6 +/- 0.8 s) than freshwater
      (35 +/- 4%, 44 +/- 1 s), but they did not differ significantly from saline medium
      (56 +/- 3%, 74.3 +/- 0.7 s) (P > 0.05). Higher eyeing rates were observed after
      the activation of sperm in ovarian fluid and saline solution than freshwater when
      35,000 or 350,000 spermatozoa per egg were added into the activation media.
      However, no significant differences were observed at higher concentrations of
      spermatozoa per egg (730,000) (P > 0.05). Also, this study showed that the
      ovarian fluid composition can be considered as a species-specific character among
      salmonid fishes. As a conclusion, the results of this study recommend the use of
      ovarian fluid or the saline solution as an activation medium in the artificial
      reproduction of Caspian brown trout.

PMID- 19169838
TI  - Comparison of two types of TPN prescription methods in preterm neonates.
AB  - OBJECTIVE: Total parenteral nutrition is commonly used in neonates' intensive
      care units for nutritional support of preterm neonates. Adequacy and safety of
      parenteral nutrition support are amongst the major concerns of neonates' therapy.
      Parenteral nutrition prescription in Greek hospitals is not based on standardized
      protocols, thus resulting in wide diversity of formulations. In this study, the
      results of utilization of standardized computerized parenteral nutrition
      protocols and regimens for neonates are compared to the results of protocols and
      regimens prescribed by individual neonatologists on neonates' outcome (weight
      changes, adequacy of parenteral nutrition, days of hospitalization, clinical
      outcome). SETTING: The study took place at "Mitera" Maternity Hospital of Greece.
      METHOD: Two groups of 30 preterm infants (28-36 weeks) with respiratory failure
      were recruited for the study. They were admitted in a Greek maternity hospital
      and they all received total parenteral nutrition support in neonates' intensive
      care unit. Standardized, computer based protocols were applied for the
      prescription of parenteral nutrition formulations in the first group, while on
      the other, regimens prescribed by neonatologists were used. MAIN OUTCOME
      MEASURES: Macro- and micronutrients provided by the different total parenteral
      nutrition protocols were recorded. Body weight was measured, blood count and
      biochemical profile were performed at the beginning and at the end of parenteral
      nutrition support. The number of days of total parenteral nutrition support as
      well as the total number of days of hospitalization was recorded. RESULTS:
      Standardized protocols provided more energy (P-value: 0.05), protein (P-value:
      0.023) and micronutrients than the non-standardised. Neonates that receive
      standardized total parenteral nutrition gained weight (+44 +/- 114 g) and had
      better blood count and biochemical values during total parenteral nutrition
      support compared to the other group, that lost weight during total parenteral
      nutrition support (-53 +/- 156 g). These differences were also statistically
      significant (P value < 0.05). Regarding the total days of hospitalization, no
      differences were found between the two groups. CONCLUSION: The use of
      standardized protocols in preterm neonates resulted in more adequate provision of
      nutrients, weight gain and better blood count profile compared with protocols
      prescribed by individual physicians.

PMID- 19169839
TI  - Fluorescence changes accompanying short-term light adaptations in photosystem I
      and photosystem II of the cyanobacterium Synechocystis sp. PCC 6803 and
      phycobiliprotein-impaired mutants: State 1/State 2 transitions and carotenoid
      induced quenching of phycobilisomes.
AB  - The features of the two types of short-term light-adaptations of photosynthetic
      apparatus, State 1/State 2 transitions, and non-photochemical fluorescence
      quenching of phycobilisomes (PBS) by orange carotene-protein (OCP) were compared
      in the cyanobacterium Synechocystis sp. PCC 6803 wild type, CK pigment mutant
      lacking phycocyanin, and PAL mutant totally devoid of phycobiliproteins. The
      permanent presence of PBS-specific peaks in the in situ action spectra of
      photosystem I (PSI) and photosystem II (PSII), as well as in the 77 K
      fluorescence excitation spectra for chlorophyll emission at 690 nm (PSII) and 725
      nm (PSI) showed that PBS are constitutive antenna complexes of both photosystems.
      The mutant strains compensated the lack of phycobiliproteins by higher PSII
      content and by intensification of photosynthetic linear electron transfer. The
      detectable changes of energy migration from PBS to the PSI and PSII in the
      Synechocystis wild type and the CK mutant in State 1 and State 2 according to the
      fluorescence excitation spectra measurements were not registered. The constant
      level of fluorescence emission of PSI during State 1/State 2 transitions and
      simultaneous increase of chlorophyll fluorescence emission of PSII in State 1 in
      Synechocystis PAL mutant allowed to propose that spillover is an unlikely
      mechanism of state transitions. Blue-green light absorbed by OCP diminished the
      rout of energy from PBS to PSI while energy migration from PBS to PSII was less
      influenced. Therefore, the main role of OCP-induced quenching of PBS is the
      limitation of PSI activity and cyclic electron transport under relatively high
      light conditions.

PMID- 19169840
TI  - Tetrahydrobiopterin in biomedical research.

PMID- 19169842
TI  - Peripheral neuropathy in a patient with D-2-hydroxyglutaric aciduria.
AB  - D-2-hydroxyglutaric aciduria (D-2-HGA; OMIM 600721) is a rare autosomal recessive
      neurometabolic disorder with a wide clinical spectrum. The severe phenotype is
      homogeneous and is characterized by early infantile-onset epileptic
      encephalopathy with hypotonia, delayed cerebral visual development,
      cardiomyopathy and facial dysmorphic features. The mild phenotype has a more
      variable clinical expression with hypotonia and developmental delay. We present
      peripheral neuropathy as an additional clinical and electrophysiological feature
      in a 16-year-old boy with a homozygous missense mutation in exon 3 of the D-2
      hydroxyglutarate dehydrogenase gene (D2HGDH) at position c.458T>C. This mutation
      results in replacement of a methionine residue, which was highly conserved during
      evolution, by threonine (p.Met153Thr).

PMID- 19169843
TI  - Mitochondrial cytochrome c release: a factor to consider in mitochondrial
      disease?
AB  - The pathogenesis of mitochondrial disorders has largely focused on the impairment
      of cellular energy metabolism. However, mitochondrial dysfunction has also been
      implicated as a factor in the initiation of apoptosis due to the translocation of
      cytochrome c, from mitochondria to the cytosol, and the subsequent cleavage of
      pro-caspase 3. In this study, we determined the cytochrome c content of cytosols
      (skeletal muscle) prepared from 22 patients with evidence of compromised
      mitochondrial electron transport chain enzyme activity and 26 disease controls.
      The cytochrome c content of the mitochondrial electron transport chain-deficient
      group was found to be significantly (p < 0.02) elevated when compared with the
      control group (63.7 +/- 15.5 versus 27.7 +/- 2.5 ng/mg protein). Furthermore, a
      relationship between the cytosolic cytochrome c content of skeletal muscle and
      complex I and complex IV activities was demonstrated. Such data raise the
      possibility that mitochondrial cytochrome c release may be a feature of
      mitochondrial disorders, particularly for those patients with marked deficiencies
      of respiratory chain enzymes. Whether initiation of apoptosis occurs as a direct
      consequence of this cytochrome c release has not been fully evaluated here.
      However, for one patient with the greatest documented cytosolic cytochrome c
      content, caspase 3 could be demonstrated in the cytosolic preparation. Further
      work is required in order to establish whether a relationship also exists between
      caspase 3 formation and the magnitude of respiratory chain deficiency.

PMID- 19169844
TI  - Proposed high-risk screening protocol for Fabry disease in patients with renal
      and vascular disease.
AB  - Fabry disease is a complex, multisystemic and clinically heterogeneous disease
      with prominent urinary excretion of globotriaosylceramide (Gb(3)), the principal
      substrate of the deficient enzyme, alpha-galactosidase A. Some measure of
      specific treatment is possible with enzyme replacement therapy, which can be
      applied safely and effectively to Fabry patients. Incidence estimations of Fabry
      disease vary widely from 1:55 000 to 1:3000 male births. The true incidence is
      likely to be higher than originally thought, owing to the existence of milder
      variants of the disease. The main complications of Fabry disease are a 100-fold
      increased risk of ischaemic stroke, cardiac disease, a wide variety of
      arrhythmias, valvular dysfunction and cardiac vascular disease, as well as
      progressive renal failure usually associated with significant proteinuria. These
      clinical manifestations are non-specific and are often mistaken for symptoms of
      other disorders, thus complicating the confirmation of diagnosis. Other clinical
      features of the disease are often absent (angiokeratoma), subtle (corneal
      opacities and hypohidrosis), or unaccompanied by specific physical findings
      (acroparaesthesias) indicating the true nature of the underlying disease. We
      propose the hypothesis that alpha-galactosidase A deficiency is a modifiable
      cardiovascular risk factor in the general population. This hypothesis may be
      tested by a non-invasive high-risk screening protocol for Fabry patients with
      ischaemic strokes and a variety of cardiac, and renal complications. These
      patients would benefit from diagnosis, appropriate treatment, follow-up and
      surveillance. Early detection of Fabry patients would also benefit affected
      relatives, many of whom do not have a clear diagnosis of their clinical
      condition.

PMID- 19169846
TI  - Fungal infection of mantis shrimp (Oratosquilla oratoria) caused by two
      anamorphic fungi found in Japan.
AB  - Two fungal pathogens of the mantis shrimp (Oratosquilla oratoria) in Yamaguchi
      and Aichi Prefectures, Japan are described as the new species Plectosporium
      oratosquillae and Acremonium sp. (a member of the Emericellopsis marine clade).
      Both fungi infect the gills of the mantis shrimp, which become brown or black due
      to melanization. The former species is characterized by its slow growth on
      artificial seawater yeast extract peptone glucose (PYGS) agar, pale yellow to
      pale orange or grayish yellow colonies, short cylindrical solitary phialides with
      a wavy tip, and one-celled ellipsoidal conidia. Although lacking the two-celled
      conidia demonstrated by the type species Plectosporium tabacinum, the taxonomic
      placement of the new species was confirmed by DNA sequence analysis of the
      internal transcribed spacer (ITS) region of ribosomal DNA (ITS1, 5.8S rDNA and
      ITS2). Acremonium sp., the other causal pathogen, differs from P. oratosquillae
      by its fast growth on PYGS agar, pale orange to salmon-colored colonies, long,
      slender conidiophores consisting of solitary phialides with tips lacking an
      undulate outline, and typically cylindrical conidia. Analysis of ITS and beta
      tubulin gene sequences placed this fungus within the phylogenetically distinct
      Emericellopsis (anam. Acremonium) marine clade. Various physiological
      characteristics of both pathogens were also investigated. This is the first
      report of a fungal infection found on the mantis shrimp in Japan.

PMID- 19169847
TI  - Molecular cloning and characterization of a novel pollen predominantly membrane
      protein gene BcMF12 from Brassica campestris ssp. chinensis.
AB  - A novel membrane protein gene, BcMF12, was isolated from Chinese cabbage
      (Brassica campestris L. ssp. chinensis Makino) using rapid amplification of the
      cDNA ends based on a pollen-specific cDNA fragment (DN237936). The cDNA was 1,155
      bp in length with an open reading frame of 894 bp capable of encoding a putative
      polypeptide of 297 amino acids with an estimated molecular mass of 34.6 kDa and a
      predicted isoelectric point of 9.6. Comparative and bioinformatics analyses
      revealed that BcMF12 showed high similarities with some membrane protein
      sequences previously published in the public database and contained six highly
      conserved transmembrane domains corresponding to six highly hydrophobic regions.
      This indicates that BcMF12 may be a putative membrane protein. RNA gel blot
      analysis indicated that the transcripts of BcMF12 were abundant in the flower
      bud, flower and anther, but not detected in the root, stem, leaf and pistil.
      Moreover, the BcMF12 transcripts were detectable at the late stages of pollen
      development. Morphological investigations of pollen from the BcMF12 antisense
      transgenic plants showed that most of pollen grains of transgenic plants were
      abnormal. These results strongly suggest that BcMF12 is a novel pollen
      preferentially membrane protein which play an important role during the pollen
      development in Chinese cabbage.

PMID- 19169848
TI  - Theoretical and experimental investigation of chaperone effects on soluble
      recombinant proteins in Escherichia coli: effect of free DnaK level on
      temperature-induced recombinant streptokinase production.
AB  - Modeling and analysis of genetic networks have become increasingly important in
      the investigation of cellular processes. The genetic networks involved in
      cellular stress response can have a critical effect on the productivity of
      recombinant proteins. In this work, it was found that the temperature-inducible
      expression system for the production of soluble recombinant streptokinase in
      Escherichia coli resulted in a lower productivity compared to the chemically
      induced system. To investigate the effect of the induced cellular response due to
      temperature up-shift a model-based approach is adopted. The role played by the
      major molecular chaperone teams DnaK-DnaJ-GrpE and GroEL-GroES on the
      productivity of recombinant streptokinase was experimentally determined. Based on
      these investigations, a detailed mechanistic mathematical model was developed for
      the cellular response during the temperature-induced recombinant streptokinase
      production. The model simulations were found to have a good qualitative agreement
      with the experimental results. The mechanistic mathematical model was validated
      with the experiments conducted on a sigma(32) mutant strain. Detailed analysis of
      the parameter sensitivities of the model indicated that the level of free DnaK
      chaperone in the cell has the major effect on the productivity of recombinant
      streptokinase during temperature induction. Analysis of the model simulations
      also shows that down regulation or selective redirection of the heat shock
      proteins could be a better way of manipulating the cellular stress response than
      overexpression or deletion. In other words, manipulating the system properties
      resulting from the interaction of the components is better than manipulating the
      individual components. Although our results are specific to a recombinant protein
      (streptokinase) and the expression system (E. coli), we believe that such a
      systems-biological approach has several advantages over conventional experimental
      approaches and could be in principle extended to bigger genetic networks as well
      as other recombinant proteins and expression systems.

PMID- 19169849
TI  - In hyperthyroid rats octylguanidine protects the heart from reperfusion damage.
AB  - Hyperthyroidism sensitizes the heart for reperfusion injury. As known,
      mitochondrial permeability transition underlies reperfusion heart damage. This
      study was undertaken to explore the protective effect of octylguanidine (OG), an
      inhibitor of permeability transition, on hearts from hyperthyroid rats subjected
      to ischemia/reperfusion. Hyperthyroidism was induced by a daily injection of 2 mg
      T3/kg body weight for 5 days. OG was injected at a dose of 5 mg/kg body weight.
      It was found that the amine protects against reperfusion-induced permeability
      transition, i.e., mitochondria from hyperthyroid rats, treated with OG, retained
      accumulated Ca(2+), similarly to control mitochondria. OG maintained post
      reperfusion cardiac frequency in hyperthyroid rats at 429 +/- 16 in comparison to
      control and T3 treated rats (70 +/- 12 and 71 +/- 2, respectively). We also found
      that OG diminished the post reperfusion accumulation of IFNgamma from 34.3 +/-
      2.5 to 18.7 +/- 1.35, IL-6 from 38.5 +/- 4.5 to 15.1 +/- 0.12, IL-1 from 16.78 +/
      0.73 to 12.19 +/- 1.54, and TNFalpha from 45.05 +/- 3.14 to 29.85 +/- 4.3 (pg/50
      microg myocardial tissue). It is concluded that OG inhibits the hypersensitivity
      of the hyperthyroid myocardium to undergo reperfusion damage due to its
      inhibitory action on the permeability transition pore.

PMID- 19169850
TI  - Molecular cloning of OSP94: A significant biomarker protein of hypertensive human
      heart and a member of HSP110 family.
AB  - Heat shock proteins (HSPs) are upregulated in response to stress and play a
      protective function in refolding of cellular proteins. In hypertension, the heart
      is a vital organ that requires examination and investigation, and primary
      induction of HSPs is predominantly effected. Hypertension results from osmotic
      imbalance during renin-angiotensin cycle inefficiency. Osmotic stress protein 94
      (OSP94) is a stress protein induced upon osmotic imbalance. It is therefore
      necessary to analyze its precise role in the hypertensive heart. We have first
      reported the cloning and expression of human heart OSP94 followed by an analysis
      of gene sequence and protein homology. Directional cloning of OSP94 by PCR
      amplification yielded a 2.5 kb amplicon and was cloned into pET-15b. Site
      directed mutagenesis was essentially followed. mRNA expression levels were
      evaluated in correlation with HSPs. Gene analysis indicated a 2520 bp sequence
      with an 838-amino acid protein complement. Protein homology revealed highly
      conserved sequence similarity among mammalian sequences. Structural predictions
      of OSP94 protein were also investigated. OSP94 is therefore recognized as a
      significant stress protein for investigations in hypertensive heart tissues and
      is a highly conserved protein in the HSP110 subfamily.

PMID- 19169851
TI  - Teriflunomide reduces behavioral, electrophysiological, and histopathological
      deficits in the Dark Agouti rat model of experimental autoimmune
      encephalomyelitis.
AB  - Teriflunomide is an orally available anti-inflammatory drug that prevents T and B
      cell proliferation and function by inhibition of dihydroorotate dehydrogenase. It
      is currently being developed for the treatment of multiple sclerosis (MS). We
      report here for the first time the anti-inflammatory effects of teriflunomide in
      the Dark Agouti rat model of experimental autoimmune encephalomyelitis (EAE).
      Neurological evaluation demonstrated that prophylactic dosing of teriflunomide at
      3 and 10 mg/kg delayed disease onset and reduced maximal and cumulative scores.
      Therapeutic administration of teriflunomide at doses of 3 or 10 mg/kg at disease
      onset significantly reduced maximal and cumulative disease scores as compared to
      vehicle treated rats. Dosing teriflunomide at disease remission, at 3 and 10
      mg/kg, reduced the cumulative scores for the remaining course of the disease.
      Teriflunomide at 10 mg/kg significantly reduced inflammation, demyelination, and
      axonal loss when dosed prophylactically or therapeutically. In
      electrophysiological somatosensory evoked potential studies, therapeutic
      administration of teriflunomide, at the onset of disease, prevented both a
      decrease in waveform amplitude and an increase in the latency to waveform
      initiation in EAE animals compared to vehicle. Therapeutic dosing with
      teriflunomide at disease remission prevented a decrease in evoked potential
      amplitude, prevented an increase in latency, and enhanced recovery time within
      the CNS.

PMID- 19169852
TI  - Magnesium and aspirin treatment in patients with subarachnoid haemorrhage.
      Comparison of effects after endovascular and neurosurgical aneurysm occlusion.
AB  - OBJECTIVE: Aneurysm treatment with endovascular coiling is associated with a
      better outcome than neurosurgical clipping in patients with subarachnoid
      haemorrhage (SAH). The better outcome after coiling may decrease the risk
      reduction from other treatments in these patients, and thus may increase sample
      sizes for current or future neuroprotective trials. The influence of the method
      of aneurysm treatment was studied in our randomised MASH trial, which assessed in
      a factorial design the efficacy of magnesium and aspirin in preventing delayed
      cerebral ischaemia (DCI) and poor outcome. METHODS: Between November 2000 and
      January 2004 315 patients were enrolled in the trial; 55 of them had no aneurysm
      treatment and were excluded for the current analysis, 176 underwent neurosurgical
      and 84 endovascular treatment. The effect of treatment on the risk of DCI was
      assessed by means of Cox proportional hazards modelling and that of poor outcome
      by means of logistic regression analysis. RESULTS: The hazard ratio of DCI with
      aspirin was 1.4 (95 % CI 0.3 - 1.7) after coiling and 1.9 (0.8 - 4.4) after
      clipping, and with magnesium 0.4 (0.1 - 1.2) after coiling and 0.8 (0.4 - 1.7)
      after clipping. The odds ratio of poor outcome with aspirin was 0.7 (0.2 - 2.9)
      after coiling and 0.8 (0.3 - 2.3) after clipping, and with magnesium 0.3 (0.1 -
      1.0) after coiling and 0.8 (0.4 - 1.6) after clipping. CONCLUSION: This post hoc
      analysis does not suggest that medical treatments are less effective after
      endovascular than after neurosurgical treatment in patients with SAH, and thus do
      not support a need for adjusting sample size calculations in future trials.

PMID- 19169853
TI  - Insights into the role and function of L2, the minor capsid protein of
      papillomaviruses.
AB  - Human papillomaviruses (HPV) are responsible for the most common human sexually
      transmitted viral infections, and high-risk types are responsible for causing
      cervical and other cancers. The minor capsid protein L2 of HPV plays important
      roles in virus entry into cells, localisation of viral components to the nucleus,
      in DNA binding, capsid formation and stability. It also elicits antibodies that
      are more cross-reactive between HPV types than does the major capsid protein L1,
      making it an attractive potential target for new-generation, more broadly
      protective subunit vaccines against HPV infections. However, its low abundance in
      natural capsids--12-72 molecules per 360 copies of L1--limits its immunogenicity.
      This review will explore the biological roles of the protein, and prospects for
      its use in new vaccines.

PMID- 19169854
TI  - Chitotriosidase and gene therapy for fungal infections.
AB  - Chitotriosidase secreted by activated human macrophages has been implicated in
      the defence against chitin-bearing pathogens. The antifungal properties of human
      chitotriosidase were investigated here following retroviral vector-mediated gene
      transfer of the open reading frame of the chitotriosidase gene into Chinese
      hamster ovary cells. A chitinase assay confirmed that the engineered cells
      secreted recombinant chitotriosidase constitutively. Two dimensional gel
      electrophoresis and western blotting indicated that the recombinant protein is
      the major, chitin-binding, fifty kilodalton isoform. Culture medium conditioned
      by the transduced cells inhibited growth of isolates of Aspergillus niger,
      Candida albicans and Cryptococcus neoformans. Furthermore, longevity was
      significantly increased in a mouse model of cryptococcosis when cells transduced
      with the chitotriosidase gene and encapsulated in alginate microspheres were
      implanted subcutaneously in the animals. Engraftment of microcapsules containing
      cells transduced with the chitotriosidase gene has the potential to combat
      infections caused by chitinous pathogens through the prolonged delivery of
      recombinant chitotriosidase.

PMID- 19169855
TI  - Contribution of the daily melatonin profile to diagnosis of tumors of the pineal
      region.
AB  - Tumors of the pineal region (TPR) include different entities: germ cell tumors
      (GCT), pineal parenchymal tumors (PPT), meningiomas, and glial tumors. Except for
      GCT, there are no peripheral markers and histopathological diagnosis needs biopsy
      or surgery. We studied daily melatonin variations in twenty-nine patients with
      TPR and five with tectal plate glioma (TPG), used as controls, before and/or
      after surgery. Before surgery, a melatonin nycthemeral rhythm was observed in
      patients with TPG and TPR (one cyst, three PPT, one papillary tumor of the pineal
      region, two meningiomas, six gliomas). Melatonin rhythm was dramatically reduced
      for undifferentiated or invasive tumors. After surgery, the absence of melatonin
      variation in some cases could be the consequence of pineal damage by surgery. The
      contribution of determination of melatonin profiles to the diagnosis of TPR
      remains limited but of interest. The evidence for melatonin deficiency could
      justify melatonin administration to prevent the postpinealectomy syndrome.

PMID- 19169856
TI  - Concurrent capecitabine and whole-brain radiotherapy for treatment of brain
      metastases in breast cancer patients.
AB  - Preclinical data have demonstrated that ionizing radiation acts synergistically
      with capecitabine. This report retrospectively assessed the use of capecitabine
      concurrently with whole-brain radiotherapy (WBRT) in patients with brain
      metastases from breast cancer. From January 2003 to March 2005, five breast
      cancer patients with brain metastases were referred for WBRT with concurrent
      capecitabine. Median age was 44 years (range: 38-53). The median dose of
      capecitabine was 1,000 mg/m(2) twice daily for 14 days (day1-14). Treatment
      cycles were repeated every 21 days, concurrently with WBRT (30 Gy, 3 Gy per
      fraction, 5 days per week). Median survival after starting WBRT plus capecitabine
      was 6.5 months (range 1-34 months). One patient achieved a complete response. Two
      patients achieved partial response, including one with local control lasting
      until most recent follow-up. One patient had stable disease. The remaining
      patient was not assessable for response because of early death. Most commonly
      reported adverse events were nausea (n = 2) and headache (n = 2), always grade 1.
      Other toxicities were grade 3 hand/foot syndrome (n = 1), moderate anemia
      requiring transfusion and dose reduction of capecitabine (n = 1), and grade 1
      mucositis (n = 1). Although promising, these preliminary data warrant further
      assessment of capecitabine-based chemoradiation in brain metastases from breast
      cancer and need to be further validated in the setting of a clinical trial.

PMID- 19169858
TI  - Sequence analysis of human TRPV6 suggests positive selection outside Africa.

PMID- 19169857
TI  - RNA interference inhibits yellow fever virus replication in vitro and in vivo.
AB  - RNA interference (RNAi) is a process that is induced by double stranded RNA and
      involves the degradation of specific sequences of mRNA in the cytoplasm of the
      eukaryotic cells. It has been used as an antiviral tool against many viruses,
      including flaviviruses. The genus Flavivirus contains the most important
      arboviruses in the world, i.e., dengue (DENV) and yellow fever (YFV). In our
      study, we investigated the in vitro and in vivo effect of RNAi against YFV. Using
      stable cell lines that expressed RNAi against YFV, the cell lines were able to
      inhibit as much as 97% of the viral replication. Two constructions (one against
      NS1 and the other against E region of YFV genome) were able to protect the adult
      Balb/c mice against YFV challenge. The histopathologic analysis demonstrated an
      important protection of the central nervous system by RNAi after 10 days of viral
      challenge. Our data suggests that RNAi is a potential viable therapeutic weapon
      against yellow fever.

PMID- 19169859
TI  - Genetic diversity of red-bellied Titis (Callicebus moloch) from Eastern Amazonia
      based on microsatellite markers.
AB  - The titi monkeys (Callicebus spp.) are a large, diverse genus of platyrrhines,
      widely distributed in tropical South America. The genetic variability of these
      monkeys is still relatively poorly known, especially at the population level. In
      the present study, four heterologous microsatellite markers were used to
      investigate genetic diversity in 23 individuals from a wild population of red
      bellied titis (Callicebus moloch) in eastern Amazonia. An unexpectedly low level
      of diversity was found. The average number of alleles was 8.75 (range: 5-15), and
      the average heterozygosity was 0.33 (range: 0.09-0.65). This preliminary
      information suggests a reduction of the potential for long-term survival of the
      population and indicates the putative necessity of implementation of a species
      conservation program.

PMID- 19169860
TI  - Sequence analysis of the plasmid pGY1 harbored in Salmonella enterica serovar
      paratyphi A.
AB  - The cryptic plasmid pGY1, which is harbored by a clinical isolate of Salmonella
      enterica serovar Paratyphi A, was identified in a 9-year-old girl with
      paratyphoid fever in 2005, and its DNA sequence was determined. It is 3592 bp in
      length and had a G+C content of 43.3%. Three ORFs were predicted that share low
      similarity with hypothetical proteins in the GenBank database. pGY1 shared 36.6%
      sequence homology with the cryptic plasmid pIMVS1 from Salmonella typhimurium.
      Its unique sequence makes it attractive for further study to obtain insight into
      the evolutionary relationship of this plasmid with other Enterobacteriaceae
      plasmids.

PMID- 19169861
TI  - Isolation and expression of a novel alligator gene belonging to the Sox gene
      family.
AB  - Sox genes share a highly conserved DNA-binding motif, the HMG (high mobility
      group)-box domain, and have diverse roles in vertebrate embryonic development. A
      novel SRY-related cDNA (temporarily called Sox33) isolated from the Chinese
      alligator (Alligator sinensis) is 1,819 bp in length, with an open reading frame
      from 220 to 1113 bp, encoding a protein of 298 amino acids. Two putative
      polyadenylation signal sequences (AATAAA) are present upstream of the poly(A)
      tail in the 3' UTR (at 1255-1260 and 1774-1779). The putative protein contains an
      HMG-box domain most closely related to hSox12, mSox4, rtSox11, and mSox11
      homologs, indicating that alligator Sox33 belongs to group C in the Sox gene
      family. Alligator adult and developing tissues were tested for Sox33 mRNA by
      independent Northern blots using a 336-bp probe (at 907-1243) between the HMG-box
      and the poly(A) site I and a 277-bp probe (at 1477-1754) between the two
      polyadenylation sites. Two transcripts (1.3 kb and 1.8 kb) in developing brain
      and one (1.8 kb) in adult brain were identified by the 336-bp probe; only one
      transcript (1.8 kb) in developing and adult brains was detected by the 277-bp
      probe. The results suggest that alligator Sox33 may use a different
      polyadenylation mechanism in the developing brain and play a role in the
      development and maintenance of the nervous system.

PMID- 19169862
TI  - Role of residual vitreous cortex removal in prevention of postoperative vitreous
      hemorrhage in diabetic vitrectomy.
AB  - AIM: To evaluate whether residual vitreous cortex removal has a role in the
      prevention of postoperative vitreous hemorrhage in diabetic vitrectomy. METHODS:
      Retrospective, comparative, nonrandomized study on a consecutive series of
      patients who underwent vitrectomy for diabetic eye disease. Recurrence of
      postoperative vitreous hemorrhage was compared in patients following surgery with
      and without residual vitreous cortex removal. RESULTS: During the study period,
      59 patients had vitrectomy for diabetic disease. In 31 patients (group 1), the
      residual vitreous cortex was not removed and in 28 patients (group 2) the
      residual vitreous cortex was removed during surgery. Both groups were matched for
      number of patients, age, sex, duration of follow-up, and diagnosis. Recurrent
      postoperative vitreous hemorrhage (RVH) was noted in ten patients in group 1
      (10/31, 32.25%) and in two patients in group 2 (2/28, 7.14%). The difference in
      postoperative vitreous hemorrhage between the two groups was statistically
      significant (P = 0.017). Logistic regression analysis showed that residual
      vitreous cortex removal and presence of intravitreal gas tamponade were
      associated with reduced risk of postoperative vitreous hemorrhage. However, only
      residual vitreous cortex removal was statistically significant factor in reducing
      risk of postoperative vitreous hemorrhage [odds ratio = 0.174; confidence
      interval (CI) = 0.0331-0.919; P = 0.040]. CONCLUSION: Residual vitreous cortex
      removal may be beneficial in reducing recurrence of postoperative vitreous
      hemorrhage following diabetic vitrectomy. Further randomized studies should be
      performed to evaluate the potential of this surgical technique in preventing
      postoperative recurrent vitreous hemorrhage following diabetic vitrectomy.

PMID- 19169863
TI  - Case of lacrimal gland inflammation associated with ulcerative colitis.
AB  - We report a case of lacrimal gland pseudotumor as the presenting sign of
      ulcerative colitis. A 25-year-old woman presented with a right upper eyelid
      swelling and pain. Intravenous administration of prednisolone was initiated on
      suspicion of lacrimal gland inflammation (pseudotumor). Although the treatment
      markedly reduced her ocular symptoms, she developed lower abdominal cramping and
      diarrhea with the 5 mg/day of oral prednisolone. Sigmoid colonoscopy and colon
      biopsy led to make a diagnosis of ulcerative colitis. Ulcerative colitis improved
      significantly with increased dose of steroid and additive mesalazine therapy.
      Ulcerative colitis should be included in the differential diagnosis of lacrimal
      gland pseudotumor.

PMID- 19169864
TI  - Glycerol-assisted hydrophobic interaction chromatography improving refolding of
      recombinant human granulocyte colony-stimulating factor.
AB  - Efficient refolding of recombinant proteins in the forms of inclusion bodies at
      higher concentration remains challenging. Here, we report a strategy of a dual
      gradient hydrophobic interaction chromatography (HIC) mode to refold recombinant
      human granulocyte colony-stimulating factor from its inclusion bodies at high
      protein concentration. The strategy was taken to meet the demand of dynamic
      refolding proceeding by gradually decrease the denaturant (guanidine-HCl)
      concentration and gradually increase the hydrophilicity of media (column of Poros
      PE 20) with glycerol as additive to provide a mild refolding surroundings.
      Compared with dilution method, this dual-gradient HIC process gave about 8.5-fold
      of increase in specific activity and 30% increase in soluble protein recovery.
      Furthermore, much higher protein concentration could be obtained at the same
      time.

PMID- 19169877
TI  - Divergent flow isoelectric focusing: fast and efficient method for protein sample
      preparation for mass spectrometry.
AB  - A study of complex protein mixtures obtained from biological samples by MS
      demands proper purification and separation technique. The method of divergent
      flow isoelectric focusing (DF IEF) promises improvement of sample preparation in
      proteomic studies. DF IEF was carried out in a separation channel with increasing
      width. The channel was cut out from a polyester nonwoven web. DC voltage (800 V)
      was brought to two pairs of electrodes situated on the channel sides. Amphoteric
      compounds, including proteins, drift through the channel carried by flow (18-25
      ml/h) in streamlines given by their isoelectric points. The pH gradient (3-10)
      and its stability during analysis have been monitored with colored low-molecular
      mass pI markers. Separated fractions were collected in ten microvials and further
      analyzed by MS. The suggested method was used for separation and purification of
      crude protein extract from barley grain, malt, and beer. Collected fractions of
      separated proteins were characterized by MALDI-MS. Desalting during IEF enhanced
      significantly the quality of mass spectra. It also simplified monitoring of post
      translational modifications and protein changes occurring during malting and
      brewing. Results have shown the real potential of the suggested DF IEF device lay
      out as an efficient preparative tool for separation and purification of complex
      protein mixtures for further analyses.

PMID- 19169878
TI  - -509C>T polymorphism in the TGF-beta1 gene promoter, impact on the hepatocellular
      carcinoma risk in Chinese patients with chronic hepatitis B virus infection.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors
      worldwide. The risk for developing HCC increases with severity of inflammation
      and fibrosis. Transforming growth factor-beta1 (TGF-beta1) is most frequently
      upregulated in tumor cells. The most studied -509C>T polymorphism of TGF-beta1
      gene has been associated with colorectal, gynecologic, and lung cancers. To
      assess whether this polymorphism in TGF-beta1 gene is associated with
      susceptibility to and/or clinicopathologic characteristics of HBV-related HCC, a
      total of 575 patients with chronic HBV infection and 299 healthy volunteers with
      no evidence of recent or remote HBV infection were prospectively enrolled. The
      patients were divided into two groups: those without (n = 196) and those with HCC
      (n = 379). These 379 HCC patients with chronic HBV infection were designated as
      cases, the remaining 196 patients without HCC and 299 healthy volunteers served
      as disease and healthy controls, respectively. -509C>T polymorphism in the TGF
      beta1 gene promoter was studied using restriction fragment-length polymorphism.
      In addition, tumor tissues of liver (n = 60) were obtained from the studied HCC
      patients for measurement of TGF-beta1 mRNA expression levels. We also assessed
      the plasma TGF-beta1 levels of HBV patients without (n = 94) or with HCC (n =
      136) and healthy subjects (n = 120). In our study group, the risk of HCC in
      Chinese patients with HBV infection was significantly lower with the TT genotypes
      than in those with the CC genotypes at position -509 of TGF-beta1 gene (P =
      0.01). In addition, in the case group, patients with the CC genotype had a
      statistically significant higher median plasma TGF-beta1 or liver tumor tissue
      TGF-beta1 mRNA level compared with the individuals with the TT genotype. However,
      in a subsequent analysis of the association between this polymorphism and
      clinicopathological characteristics including tumor number, size, grade, stage,
      and invasiveness, there was no significant difference in both the distribution of
      genotype or allelic frequency within HCC patients, indicating that -509C>T
      exchange in TGF-beta1 gene may play an important role in the occurrence, not the
      progression of HBV-related HCC through influencing plasma concentrations of TGF
      beta1 or TGF-beta1 mRNA expression of liver tumor tissue.

PMID- 19169876
TI  - Disruption of latent inhibition induced by ovariectomy can be reversed by
      estradiol and clozapine as well as by co-administration of haloperidol with
      estradiol but not by haloperidol alone.
AB  - INTRODUCTION: Epidemiological and clinical life cycle studies have indicated that
      the more favorable illness course and the better response to antipsychotic drugs
      (APDs) in women with schizophrenia correlate with high levels of estrogen,
      whereas increased vulnerability to exacerbation and relapse and reduced
      sensitivity to treatment are associated with low estrogen levels. Accordingly,
      the estrogen hypothesis of schizophrenia proposes that estrogen has a
      neuroprotective effect in women vulnerable to schizophrenia. MATERIALS AND
      METHODS: Latent inhibition (LI), the capacity to ignore stimuli that received
      nonreinforced preexposure prior to conditioning, is disrupted in acute
      schizophrenia patients and in rats and humans treated with the psychosis inducing
      drug amphetamine. Disruption of LI is reversible by typical and atypical APDs.
      The present study tested whether low levels of estrogen induced by ovariectomy
      (OVX) would lead to disruption of LI in female rats and whether such disruption
      would be normalized by estrogen replacement treatment and/or APDs. RESULTS:
      Results showed that OVX led to LI disruption, which was reversed by 17beta
      estradiol (150 microg/kg) and the atypical APD clozapine (5 mg/kg), but not by
      the typical APD haloperidol (0.1, 0.2, 0.3 mg/kg). Haloperidol regained efficacy
      when administered with 17beta-estradiol (50 microg/kg). DISCUSSION: These results
      provide the first demonstration in rats that low levels of hormones can induce a
      pro-psychotic state that is resistant to at least typical antipsychotic
      treatment. This constellation may mimic states seen in schizophrenic women during
      periods associated with low levels of hormones such as the menopause.

PMID- 19169879
TI  - Screening and identification of novel B cell epitopes in human heparanase and
      their anti-invasion property for hepatocellular carcinoma.
AB  - BACKGROUND: The aim of this study was to screen and identify novel B cell
      epitopes within the human heparanase protein and to investigate the impact of
      self-developed anti-heparanase polypeptide antibodies on growth and invasion of
      HCCLM6 human hepatocellular carcinoma cells in vitro. METHODS: The flexible
      regions of secondary structure and the B cell epitopes of the human heparanase
      amino acid sequence were predicted by DNAStar and Bcepred software.The multiple
      antigenic peptides (MAP) of the epitopes were synthesized in eight-branched form.
      Rabbits were immunized with the eight-branched MAPs mixed with the universal T
      helper epitope human IL-1beta peptide (VQGEESNDK, amino acid 163-171). The
      immunogenicity of the synthesized peptides was evaluated by ELISA, western blot
      and immunohistochemistry. The impact of the self-developed rabbit anti-heparanase
      polyclonal antibodies on growth and invasion ability of HCCMLM6 cells were
      analyzed in a cell culture model. The cells were first treated with one of the
      three antibodies, respectively, and then measured by using MTT, flow cytometry,
      plate clone formation, invasion assay and heparan sulfate degrading enzyme assay.
      RESULTS: The three amino acid sequences 1-15 (MAP1), 279-293 (MAP2), and 175-189
      (MAP3) in the large subunit of the human heparanase protein were predicted as its
      most potential epitopes. ELISA, western blot and immunohistochemistry analysis
      showed that all three MAPs were capable to induce high titer of serum antibodies.
      Antibodies induced by MAP1 and MAP2 were high specific. Furthermore, anti-MAP2
      antibodies showed the strongest avidity towards liver cancer tissues. Under the
      treatment with the three anti-heparanase antibodies, respectively, the growth,
      cell cycle and clone formation of the cells remained unchanged when compared with
      a treatment with normal rabbit IgG. However, an inhibition of cell invasiveness
      and heparanase activity could be detected under the treatment with anti-MAP1- or
      anti-MAP2-antibody (with a terminal concentration of 100 mug/ml). The cell
      invasiveness was decreased by 54 and 38%, respectively, the heparanase activity
      by 43 and 39%, respectively. CONCLUSION: The multiple antigenic peptides MAP1 (AC
      1-15) and MAP2 (AC 279-293) may be the dominant B cell epitopes in the human
      heparanase protein. The induced polypeptide antibodies can effectively inhibit
      the heparanase activity of HCCLM6 liver cancer cells and therefore influence
      their invasion ability, which provides a theoretic basis for the development of
      anti-heparanase antibodies and their clinical use as vaccine.

PMID- 19169880
TI  - Single- and multiple-dose disposition kinetics of sunitinib malate, a
      multitargeted receptor tyrosine kinase inhibitor: comparative plasma kinetics in
      non-clinical species.
AB  - PURPOSE: The purpose of these extensive non-clinical studies was to assess
      pharmacokinetics and dispositional properties of sunitinib and its primary active
      metabolite (SU12662). METHODS: Sunitinib was administered in single and repeat
      oral doses in mice, rats, and monkeys. Assessments were made using liquid
      chromatography-tandem mass spectrometric methods, radioactive assays, and
      quantitative whole body autoradiography. RESULTS: Sunitinib was readily absorbed
      with good oral bioavailability and linear kinetics at clinically-relevant doses.
      SU12662 plasma levels were less than those of sunitinib in mice and monkeys, but
      greater in rats. Sunitinib was extensively distributed with moderate-to-high
      systemic clearance and eliminated primarily into feces. Single- and repeat-dosing
      kinetics were similar. A prolonged half-life allowed once-daily dosing, enabling
      adequate systemic exposure with limited-to-moderate accumulation. In multiple
      dose studies with cyclic dosing, drug plasma concentrations cleared from one
      cycle to the next. CONCLUSIONS: Sunitinib exhibited advantageous pharmacokinetic
      and dispositional properties in non-clinical species, translating into favorable
      properties in humans.

PMID- 19169881
TI  - Treatment outcomes in patients with non-infectious aortic valvulitis undergoing
      aortic valve replacement: implication for the treatment of aortic valve
      involvement in Behcet's disease.

PMID- 19169882
TI  - The efficacy and safety of leflunomide therapy in lupus nephritis by repeat
      kidney biopsy.
AB  - To evaluate the clinical and pathological efficacy, and safety of leflunomide as
      a new immunosuppressive medicine in lupus nephritis (LN). A total of 31 patients
      were all determined as LN by kidney biopsy. SLE disease activity index (SLEDAI),
      clinical and immunological tests of these patients were performed. Meanwhile, the
      pathological presentation and LN activity of before and after leflunomide therapy
      were evaluated by repeat biopsy. The patients of LN usually have a bit response
      by the first or second month visit and have a good response by the third month
      visit after leflunomide therapy. One year later SLEDAI scores of all patients
      were significantly improved and 13 patients of them were transformed from complex
      pathological types to simple types (the transformed ratio was 41.9%). For the
      other patients not transformed, the pathological presentation took a favorable
      turn, the pathological active index (AI) of LN were significantly improved. There
      was not anyone relapsed or aggravated. The side effects of leflunomide were less
      and mild, and could be improved by symptomatic management with or without
      decreasing dosage. The clinical and pathological activity of LN can be apparently
      inhibited and the relapse can be prevented through leflunomide therapy. The side
      effects of leflunomide are mild and transient. Leflunomide is now a new ideal
      immunosuppressive medicine in the therapy of LN.

PMID- 19169883
TI  - Dewetting of polymer films by ion implantation.
AB  - We report dewetting of thermodynamically stable, thick (approximately 100 nm)
      polystyrene films by titanium ion implantation. The dynamic dewetting patterns in
      time evolution are recorded. The dewetting mechanism is determined to be
      heterogeneous nucleation, where the defects and Ti nanoparticles formed by ion
      implantation serve as the nuclei. In addition, we observe abundant rims with
      regular polygonal shapes in dewetting patterns. This is attributed to fingering
      instability, which results from the balance between the driving force arisen from
      thermally induced surface tension gradient and the resistive forces from the
      combination of friction force, Laplace pressure and long-range van der Waals
      interactions. Finally, a model based on mass conservation is used to
      qualitatively describe the transition from circular to polygonal shaped rims at a
      critical diameter for holes.

PMID- 19169884
TI  - Persistence of retinal function after selective ophthalmic artery chemotherapy
      infusion for retinoblastoma.
AB  - PURPOSE: To assess potential retinal viability by electroretinography following
      selective ophthalmic artery chemotherapy infusion for retinoblastoma. METHODS:
      Uncontrolled prospective case series. Patients with advanced retinoblastoma were
      offered elective ophthalmic artery chemotherapy infusion treatment under an IRB
      approved protocol as an alternative to enucleation. The ophthalmic artery was
      cannulated under fluoroscopic control, and chemotherapeutic agents (melphalan and
      occasionally carboplatin) were directly infused at doses resulting in very high
      local tissue concentrations, but low systemic drug levels. Eyes were examined
      under anesthesia at 1-month intervals, and re-treated as indicated, up to a
      maximum of six infusions. Electroretinograms were obtained during examination
      under anesthesia, using ERG-jet contact lens electrodes and a hand-held mini
      ganzfeld stimulator. The ERG protocol was similar to ISCEV standards except for
      briefer adaptation times as necessary to reduce the total anesthesia duration.
      RESULTS: We report initial results in the first ten patients attempted. Nine eyes
      were successfully cannulated and perfused. ERG data for these nine patients are
      reported. [Clinical results have been published elsewhere.] Follow up ranged from
      3 to 14 months. Extensive, often total, retinal detachments were present in many
      of the treated eyes. While regression of tumor mass and vitreous seeds was
      observed in nearly all the patients, retinal detachment occasionally persisted.
      ERG responses were extinguished in these eyes. Eyes with largely attached
      retinas, notwithstanding the presence of large tumors at baseline, remained free
      of detachment after treatment. Normal or near-normal ERGs in these eyes were
      repeatedly obtained. Recovery of ERG amplitudes was observed in three patients
      following treatment. CONCLUSIONS: Retinal function can persist and even recover
      following selective ophthalmic artery chemotherapy infusion for retinoblastoma.
      Further work is indicated to determine optimal dosing regimens, maximal tolerated
      dosage, and subsequent visual function in these patients.

PMID- 19169885
TI  - Adenoviral transduction of hTGF-beta1 enhances the chondrogenesis of bone marrow
      derived stromal cells.
AB  - TGF-beta1 plays a necessary and important role in the induction of chondrogenic
      differentiation of bone marrow stromal cells (BMSCs). In this study, porcine
      BMSCs were infected with a replication-deficient adenovirus expression vector
      carrying the hTGF-beta1 gene. The transduced BMSCs were cultured as pelleted
      micromasses in vitro for 21 days, seeded onto disk-shaped PGA scaffolds for 3
      days and subsequently implanted into the subcutaneous tissue of mice. BMSCs
      transduced with AdhTGF-beta1 expressed and secreted more hTGF-beta1 protein in
      vitro than those of the control group. Histological and immunohistological
      examination of the pellets revealed robust chondrogenic differentiation. Tissues
      made from cells transduced with AdhTGF-beta1 exhibited neocartilage formation
      after 3 weeks in vivo. The neocartilage occupied 42 +/- 5% of the total tissue
      volume which was significantly greater than that of the control group.
      Furthermore, there was extensive staining for sulfated proteoglycans and type II
      collagen in the AdhTGF-beta1 group compared to controls, and quantification of
      GAG content showed significantly greater amounts of GAG in experimental groups.
      The results demonstrate that transfer of hTGF-beta1 into BMSCs via adenoviral
      transduction can induce chondrogenic differentiation in vitro and enhance
      chondrogenesis in vivo.

PMID- 19169886
TI  - Effect of alpha-tocopherol on the synthesis of phosphatidylglycerol catalyzed by
      phospholipase D in an aqueous system.
AB  - Phosphatidylglycerol (PG) was synthesized from several phosphatidylcholines (PCs)
      via phospholipase D (PLD)-catalyzed transphosphatidylation in an aqueous system.
      The yield of PG were 71 and 68 mol% from soybean PC and egg yolk PC,
      respectively, under the optimum reaction conditions of 50 micromol PC, 10 mmol
      glycerol, 3 ml of acetate buffer, 1.6 U PLD, and 30 micromol CaCl(2) at 37
      degrees C for 48 h. In case of salmon roe PC with 14.3% eicosapentaenoic acid and
      26.8% docosahexaenoic acid, the PG yield increased to 94 mol% by addition of 46
      mumol alpha-tocopherol, although the PG yield was only 10% in absence of alpha
      tocopherol.

PMID- 19169887
TI  - Quantitative identification of teratoma tissues formed by human embryonic stem
      cells with TeratomEye.
AB  - An automated vision system, TeratomEye, was developed for the identification of
      three representative tissue types: muscle, gut and neural epithelia which are
      commonly found in teratomas formed from human embryonic stem cells. Muscle
      tissue, a common structure was identified with an accuracy of 90.3% with high
      specificity and sensitivity greater than 90%. Gut epithelia were identified with
      an accuracy of 87.5% with specificity and sensitivity greater than 80%. Neural
      epithelia which were the most difficult structures to distinguish gave an
      accuracy of 47.6%. TeratomEye is therefore useful for the automated
      identification of differentiated tissues in teratoma sections.

PMID- 19169888
TI  - Zn finger-based direct detection system for PCR products of Salmonella spp. and
      the Influenza A virus.
AB  - We have detected PCR products from Salmonella spp. and Influenza A virus using Zn
      finger protein Zif268 and Sp1, respectively. Previously, we demonstrated a novel
      method of rapid and specific detection of PCR products from Legionella
      pneumophila genome using Zn finger protein Sp1. In principle, this methodology
      might be applied to the detection of most bacteria and viruses using various Zn
      finger proteins. Here, to demonstrate the wider applicability of our method, we
      detected PCR products from Salmonella spp. and the Influenza A virus. BLAST data
      indicated the Zif268 and Sp1 recognition sequence were located on the gyrB gene
      of Salmonella spp. and the nucleoprotein gene of Influenza A virus, respectively.
      The PCR products from the oligonucleotide corresponding to the gyrB gene of
      Salmonella spp. or the nucleoprotein gene of the Influenza A virus could be
      specifically detected by ELISA or fluorescence depolarization measurement using
      Zif268 or Sp1. These results indicate the wide applicability of our novel
      methodology.

PMID- 19169889
TI  - Engineering of a multifunctional hemicellulase.
AB  - To engineer a multifunctional xylan-degrading enzyme, a chimera was created by
      fusing the xylanase domain of the Clostridium thermocellum xylanase (xynZ) and a
      dual functional arabinofuranosidase/xylosidase (DeAFc; from a compost starter
      mixture) through a flexible peptide linker. The xylanase domain of xynZ possesses
      previously unreported endoglucanase activity. The chimera, possessing the
      activities of xylanase, endoglucanase, arabinofuranosidase and xylosidase, was
      expressed in E. coli and purified. The chimera closely resembled the parental
      enzymes in pH, temperature optima and kinetics, and was more active than the
      parental enzyme mixture in the hydrolysis of natural xylans and corn stover.

PMID- 19169890
TI  - Entrapment of cytochrome P450 BM-3 in polypyrrole for electrochemically-driven
      biocatalysis.
AB  - In vitro biocatalysis with cytochrome P450 BM-3 was investigated aiming for the
      substitution of the expensive natural cofactor NADPH by electrochemistry. The
      monooxygenase was immobilized on electrodes by entrapment in polypyrrole as a
      conductive polymer for electrochemically wiring the enzyme. Electropolymerization
      of pyrrole proved to be a useful means of immobilising an active cytochrome P450
      BM-3 mutein on platinum and glassy carbon electrodes without denaturation.
      Repeatedly sweeping the electric potential between -600 and +600 mV versus
      Ag/AgCl led to enzymatically-catalysed product formation while in the absence of
      the enzyme no product formed under otherwise identical conditions.

PMID- 19169891
TI  - Detection of living Salmonella cells using bioluminescence.
AB  - ATP-based bioluminescence using mutant firefly luciferase was combined with an
      immunochromatographic lateral flow test strip assay for Salmonella enteritidis
      detection. In this combination method, the Salmonella-antibody-gold complex
      captured at the test line on the test strip was lysed by heat-treatment, and the
      ATP released from the cells was measured using mutant luciferase. This method
      resulted in approximately 1,000 times higher sensitivity in the detection of
      Salmonella (i.e. 10(3) c.f.u./ml) compared to immunochromatographic lateral flow
      assay.

PMID- 19169892
TI  - Agrobacterium-mediated transformation of embryogenic tissues of hybrid firs
      (Abies spp.) and regeneration of transgenic emblings.
AB  - A genetic transformation system has been developed for selected embryogenic cell
      lines of hybrids Abies alba x A. cephalonica (cell lines AC2, AC78) and Abies
      alba x A. numidica (cell line AN72) using Agrobacterium tumefaciens. The cell
      lines were derived from immature or mature zygotic embryos on DCR medium
      containing BA (1 mg l(-1)). The T-DNA of plant transformation vector contained
      the beta-glucuronidase reporter gene under the control of double dCaMV 35S
      promoter and the neomycin phosphotransferase selection marker gene driven by the
      nos promoter. The regeneration of putative transformed tissues started
      approximately 1 week after transfer to the selection medium containing 10 mg
      geneticin l(-1). GUS activity was detected in most of the geneticin-resistant sub
      lines AN72, AC2 and AC78, and the transgenic nature of embryogenic cell lines was
      confirmed by PCR approach. Plantlet regeneration from PCR-positive embryogenic
      tissues has been obtained as well. The presence of both gus and nptII genes was
      confirmed in 11 out of 36 analysed emblings.

PMID- 19169893
TI  - Inhibition of ovarian cancer cell metastasis by a fusion polypeptide Tat-ELP.
AB  - Tumor cell metastasis is a complex, multi-step process that is a major cause of
      death and morbidity amongst cancer patients. Cell adhesion plays a critical role
      in the development of metastatic cancer, and it is mediated by interactions
      between receptors on the cell surface and ligands of the extracellular matrix or
      other surfaces. Therefore, inhibition of the cell adhesion process appears to be
      an effective method of preventing metastasis. This work describes a genetically
      engineered polypeptide with the potential to prevent cell adhesion and inhibit
      metastasis. We have found that the cell penetrating peptide Tat, fused with
      elastin-like polypeptide (ELP) inhibited adhesion, spreading, invasion and
      migration of SKOV-3 ovarian cancer cells in cell culture. Furthermore, we have
      also confirmed that Tat-ELP has anti-metastatic potential in an experimental
      ovarian cancer metastasis model in vivo, causing approximately 80% reduction in
      the tumor burden. Since cell attachment is an important step in tumor cell
      invasion and metastasis, these results suggest a novel role of Tat-ELP as a
      therapeutic intervention in cancer metastasis.

PMID- 19169894
TI  - Characterization of an animal model of aggressive metastatic pheochromocytoma
      linked to a specific gene signature.
AB  - Pheochromocytomas are chromaffin cell-derived neuroendocrine tumors. There is
      presently no cure for metastatic pheochromocytoma and no reliable way to
      distinguish malignant from benign tumors before the development of metastases. In
      order to successfully manage pheochromocytoma, it is necessary to better
      understand the biological determinants of tumor behavior. For this purpose, we
      have recently established a mouse model of metastatic pheochromocytoma using tail
      vein injection of mouse pheochromocytoma (MPC) cells. We optimized this model
      modifying the number of cells injected, length of trypsin pre-treatment, and
      incubation temperature and duration for the MPC cells before injection, and by
      serial passage and re-selection of tumors exhibiting the metastatic phenotype. We
      evaluated the effect of these modifications on tumor growth using serial in vivo
      Magnetic Resonance Imaging studies. These results show that number of cells
      injected, the pre-injection incubation temperature, and duration of trypsin
      treatment are important factors to produce faster growing, more aggressive tumors
      that yielded secondary metastatic lesions. Serial harvest, culture and re
      selection of metastatic liver lesions produced even more aggressive
      pheochromocytoma cells that retained their biochemical phenotype. Microarray gene
      expression comparison and quantitative real-time PCR of these more aggressive
      cells to the MPC-parental cell line identified genes that may be important for
      the metastatic process.

PMID- 19169895
TI  - Delayed exposure to infections and childhood lymphomas: a case-control study.
AB  - OBJECTIVES: Delayed exposure to common infections during childhood, have been
      implied to cause strong immunological response to a single infectious agent that
      eventually triggers leukemogenesis. The aim of the present study was to
      investigate whether decreased exposure to infections, as reflected in a more
      seronegative spectrum to several common infectious agents, is associated with
      increased risk for the development of childhood lymphomas. METHODS: All 125
      children (up to 14 years old), with Hodgkin (HL, n = 52) and non-Hodgkin
      lymphomas (NHL, n = 73) diagnosed through the national network of childhood
      Hematology-Oncology units during an 8-year period were enrolled in the study
      along with 125 age- and gender-matched controls. Past exposure to nine common
      infections [respiratory syncytial virus (RSV), influenza A and B, parainfluenza
      type 1, adenovirus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes
      virus 6 (HHV6), Bartonella henselae] was assessed using serological markers.
      RESULTS: After controlling for possible confounding factors, the overall
      seronegativity status upon diagnosis was statistically significantly associated
      with NHL [odds ratio; 95% CI: 1.45 (1.10-1.93), p = 0.01] and less so with HL
      risk [odds ratio; 95% CI: 1.30 (0.83-2.05), p = 0.25]. A statistically
      significant association of seronegativity with the development of NHL was evident
      for RSV [odds ratio; 95% CI: 7.27 (1.59-33.28), p = 0.01], EBV [odds ratio; 95%
      CI: 6.73 (1.45-31.20), p = 0.01] and suggestive association for influenza B [odds
      ratio; 95% CI: 2.60 (0.90-7.55), p = 0.08] and influenza A [odds ratio; 95% CI:
      2.35 (0.81-6.80), p = 0.11]. In contrast, there was no evidence for association
      of HL with negative serology for any of the infectious agents tested.
      CONCLUSIONS: The risk of lymphomas, especially NHL, might be higher when, due to
      lower exposure to several infectious agents, the relatively unmodulated immune
      system of a child is challenged by environmental stimuli that can trigger
      development of lymphomas. The results, however, need further confirmation,
      through more pertinent methodological designs.

PMID- 19169896
TI  - Previous pulmonary disease and family cancer history increase the risk of lung
      cancer among Hong Kong women.
AB  - Chinese women in Hong Kong have among the highest incidence and mortality of lung
      cancer in the world, in spite of a low prevalence of smoking. We carried out this
      population-based case-control study to evaluate the associations of previous lung
      disease and family cancer history with the occurrence of lung cancer among them.
      We selected 212 cases that were newly diagnosed with primary lung cancer, and
      randomly sampled 292 controls from the community, frequency matched by age group.
      All the cases and controls were lifetime nonsmokers. We estimated the main
      effects of preexisting asthma, pulmonary tuberculosis, pneumonia, chronic
      bronchitis, and family lung/all cancer history, using unconditional logistic
      regression, accounting for various potential risk factors and confounders. All of
      the previous lung diseases, except chronic bronchitis, were related to an
      elevated risk for lung cancer, and the association with asthma was significant.
      Those who had more than one previous lung disease tended to be at higher risk
      than those with only one of them. Positive family history of any cancer was
      associated with over 2-fold risk than negative family history. The joint effect
      of positive history of previous pulmonary diseases and positive family cancer
      history appeared to be additive, indicating the two factors acted independently.
      The results support an etiological link of preexisting lung disease and family
      cancer history to the risk of lung cancer.

PMID- 19169897
TI  - Plant-based strategies aimed at expressing HIV antigens and neutralizing
      antibodies at high levels. Nef as a case study.
AB  - The first evidence that plants represent a valid, safe and cost-effective
      alternative to traditional expression systems for large-scale production of
      antigens and antibodies was described more than 10 years ago. Since then,
      considerable improvements have been made to increase the yield of plant-produced
      proteins. These include the use of signal sequences to target proteins to
      different cellular compartments, plastid transformation to achieve high transgene
      dosage, codon usage optimization to boost gene expression, and protein fusions to
      improve recombinant protein stability and accumulation. Thus, several HIV/SIV
      antigens and neutralizing anti-HIV antibodies have recently been successfully
      expressed in plants by stable nuclear or plastid transformation, and by transient
      expression systems based on plant virus vectors or Agrobacterium-mediated
      infection. The current article gives an overview of plant expressed HIV antigens
      and antibodies and provides an account of the use of different strategies aimed
      at increasing the expression of the accessory multifunctional HIV-1 Nef protein
      in transgenic plants.

PMID- 19169898
TI  - Netilmicin in the neonate: pharmacokinetic analysis and influence of parenteral
      nutrition.
AB  - OBJECTIVE: The aim of this study was to investigate the impact of parenteral
      nutrition on netilmicin pharmacokinetics in critically ill neonates during the
      first week of life. METHOD: A total of 200 neonates (gestational ages 26.4-41
      weeks) treated with netilmicin (4-5 mg/kg in extended dosing intervals) for
      postnatal sepsis in the first week of life received either fluid therapy or
      parenteral nutrition. Netilmicin peak and trough serum concentrations were
      monitored and netilmicin pharmacokinetic parameters were compared with and
      without parenteral nutrition. RESULTS: There were no statistically significant
      differences between the pharmacokinetic parameters of netilmicin (volume of
      distribution, elimination half-life, clearance) in critically ill neonates >32
      weeks during the first week of life that received either fluid therapy or
      parenteral nutrition. For neonates <32 weeks this comparison was not feasible as
      the majority were parenterally fed. CONCLUSION: Provision of parenteral nutrition
      (versus fluid therapy) in critically ill neonates >32 weeks did not significantly
      affect netilmicin pharmacokinetics and therefore does not require modification of
      recommended netilmicin dosage regimens.

PMID- 19169900
TI  - Mycophenolate mofetil for the treatment of autoimmune diseases: hype or hope?

PMID- 19169899
TI  - Health-related quality of life after coronary artery bypass grafting. The impact
      of a randomised controlled home-based intervention program.
AB  - OBJECTIVE: The aim of this study was to evaluate the impact of a home based
      intervention program (HBIP) on health related quality of life (HRQoL) after
      coronary artery bypass grafting (CABG). To strengthen the clinical
      interpretation, HRQoL data were compared to the general population. METHODS: In a
      randomised controlled trial (RCT), a total of 185 CABG patients (93 vs 92)
      completed the study. The intervention group received a HBIP 2 and 4 weeks after
      surgery. HRQoL was measured by the Seattle Angina Questionnaire (SAQ) and the
      Short Form 36 (SF-36) in both patient groups before surgery, at 6 weeks and 6
      months after surgery. RESULTS: Significant improvements were found in both groups
      for the majority of subscales of HRQoL at 6-week and 6-month follow-up. However,
      these improvements did not differ significantly between the groups. Compared to
      the general population, significant differences (P < 0.05) were found for the SF
      36 subscales: role physical, role emotional and bodily pain. CONCLUSIONS: HRQoL
      after CABG improved markedly over time, but no significant or clinically
      important differences were found when compared with controls. Thus, work to
      further develop and test the effect of a HBIP on HRQoL in patients undergoing
      rehabilitation following CABG is warranted.

PMID- 19169901
TI  - Pathophysiology of itching and sneezing in allergic rhinitis.
AB  - Itching and sneezing represent two of the main bothersome symptoms, apart from
      nasal obstruction and rhinorrhea in allergic rhinitis. Apparently, activation of
      the central and peripheral nervous system plays a major role in the
      pathophysiology of this process. Sensory nerves of the afferent trigeminal system
      including myelinated Adelta-fibres and thin, non-myelinated C-fibres of the nasal
      mucosa transmit signals generating sensations, including itching and motor
      reflexes, such as sneezing. These nerves can be stimulated by products of
      allergic reactions and by external physical and chemical irritants. Via axon
      reflex inflammatory neuropeptides including the tachykinins substance P (SP) and
      neurokinin A (NKA) and the calcitonin gene related peptide are released, leading
      to vasodilatation, increased vascular permeability (concept of "neurogenic
      inflammation"), glandular activation, leukocyte recruitment and differentiation
      of immune cells including mast cells, eosinophils, lymphocytes and macrophages.
      The present paper describes nasal (micro-) anatomy and innervation and explains
      the central and peripheral mechanisms initiating itching and sneezing in allergic
      rhinitis. Further, the role of neuropeptides and neurotrophins with regard to
      neuronal and immune cell activation which might play a key role in the future
      treatment of allergic rhinitis are discussed.

PMID- 19169902
TI  - Clinical experience with mycophenolate mofetil in systemic autoimmune conditions
      refractory to common immunosuppressive therapies.
AB  - OBJECTIVES: Standard therapies against inflammatory rheumatic diseases consist of
      immunosuppressive drugs with high toxicities and many side effects. Except in the
      treatment of systemic lupus erythematosus with renal involvement, controlled
      studies with mycophenolate mofetil (MMF) are lacking in other autoimmune and
      inflammatory systemic diseases. Here we describe our clinical experience with MMF
      in several unusual indications. METHODS: We collected data including serological
      findings, adverse events and response to treatment in eleven patients with
      autoimmune diseases including systemic lupus erythematosus (SLE), mixed
      connective tissue disease (MCTD), polymyositis (PM), diffuse systemic sclerosis
      that were treated in our rheumatology unit. RESULTS: Our results show remission
      in ten patients with minimal side effects and reduced prednisone dosage. The
      median dose of MMF was 2 g per day. Adverse events were limited, with one case of
      leucopenia, one tachycardia and one colitis. One patient definitively stopped the
      treatment because of side effects. CONCLUSIONS: MMF seems to be a very powerful
      and attractive alternative medication in the treatment of immune-mediated
      inflammatory diseases. The good tolerance and safety profile makes it an
      excellent therapeutic option permitting a global reduction of corticosteroids
      doses.

PMID- 19169903
TI  - What patients and relatives expect from an intensivist--the Swiss side of a
      European survey.
AB  - BACKGROUND: Until recently, patients' and families' expectations of specialists
      in intensive care medicine were largely unknown. This paper reports the results
      from the Swiss subgroup of a recently performed European multicentre study
      addressing this question. METHODS: Purposeful sample of adult ICUs in
      Switzerland. A questionnaire was distributed to ICU patients and relatives. It
      included 21 statements in the domains "medical knowledge", "communication with
      patients", "communication with relatives". Statements were rated for importance
      on a four-point Likert scale. RESULTS: All addressed ICUs participated; there
      were two from the French and eight from the German speaking part of Switzerland.
      197 questionnaires were returned (46%). Overall, the majority of characteristics
      were rated as important. As in the other participating countries, patients and
      relatives ranked, "medical knowledge" as most essential, followed by,
      "communication with patients" and, "communication with relatives". This remained
      unchanged when analysed for German or French language, female or male, age >65
      years. Female responders rated "communication" as more important than male
      responders. For French speaking participants "treating patients as individuals"
      was the most important statement. CONCLUSIONS: In accordance to respondents from
      other countries, Swiss patients and their families with experience of intensive
      care rate medical knowledge as most essential for specialists in intensive care
      medicine. However, communication with patients and with relatives is considered
      important, too. Accordingly, developing and ensuring medical knowledge and
      skills, as well as competence in communication must remain top priorities for the
      institutions responsible for training ICU physicians.

PMID- 19169904
TI  - Changes in pre-pregnancy weight and weight gain during pregnancy: retrospective
      comparison between 1986 and 2004.
AB  - QUESTIONS UNDER STUDY: To compare the incidence of pre-pregnancy overweight,
      obesity, and difference in weight gain during pregnancy in the years 1986 and
      2004, in women delivered at the maternity unit of our hospital. METHODS:
      Retrospective study. Maternity records of patients delivered in the years 1986
      and 2004 were compared. Data extraction included booking weight, height, weight
      gain, birth weight as well as information on mode of delivery and gestational age
      at delivery. RESULTS: During the year 1986 and 2004 a total of 690 and 668
      patients respectively were included in the analysis. The pre-pregnancy BMI > or
      =25 doubled over the 18-year period (from 15.9 to 30.1%). In 1986 only 2.6% of
      all pregnant women gained more than 20 kg, while in 2004 14.2% (p <0.0001) did
      so. The caesarean section rate was significantly higher in 2004 than 18 years
      earlier (28.3 and 9.3%, p <0.0001). CONCLUSIONS: We found a significant increase
      in all parameters between these two groups. Pregnant women are today heavier at
      the booking visit, are more overweight, and gain more weight during pregnancy. A
      similar trend is seen in the newborn babies, who have a higher birth weight than
      those born 18 years ago.

PMID- 19169905
TI  - Beta-blockers and the criteria of SIRS.

PMID- 19169906
TI  - Predictors of remission, normalized physical function, and changes in the working
      situation during follow-up of patients with early rheumatoid arthritis: an
      observational study.
AB  - OBJECTIVES: To evaluate possible predictors of remission, normalized physical
      function, and work change in rheumatoid arthritis (RA). METHODS: We determined in
      our early RA cohort the proportion of patients in remission [Disease Activity
      Score (DAS28)<2.6], with normalized function [Health Assessment Questionnaire
      (HAQ) = 0], and with changed working situation since disease onset. Candidate
      predictors of remission, normalized function, and work change were studied by
      subgroup comparison and logistic regression analysis, including demographics,
      education, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP)
      antibodies, treatment, and DAS28, HAQ, pain and fatigue scores (on the visual
      analogue scale, VAS). RESULTS: Median (interquartile range, IQR) disease duration
      was 18 (29) months. Of 89 patients included, 69% were in remission. DAS28, HAQ,
      pain and fatigue scores of these patients were lower throughout year 1, although
      similar at baseline, compared to patients not in remission. At month 4, more of
      these patients were already good responders. Remission at month 4 independently
      predicted remission at follow-up. Thirty-eight per cent had no functional
      limitations; compared to patients with limitations, they had a lower baseline HAQ
      and lower DAS28, HAQ, pain and fatigue scores during year 1. At month 4, more
      achieved remission or HAQ = 0. Male sex, baseline HAQ, and month 4 good European
      League Against Rheumatism (EULAR) response predicted long-term HAQ = 0, but month
      4 HAQ = 0 was the strongest independent predictor. Of the 40% with a paid job at
      baseline, 43.8% reported changes in their work situation; they had higher DAS28,
      HAQ, pain and fatigue scores during year 1. Failing a month 4 good EULAR response
      independently predicted work change. CONCLUSION: Month 4 disease response
      predicts later remission, normalized physical function, and work change in RA.

PMID- 19169907
TI  - Familial presentation of bamboo spine, peripheral calcifications, and normal
      sacroiliac joints.

PMID- 19169908
TI  - A novel mutation in the NOD2 gene associated with Blau syndrome: a Norwegian
      family with four affected members.
AB  - BACKGROUND: Blau syndrome is a chronic granulomatous disease with an autosomal
      dominant trait characterized by the triad granulomatous dermatitis, arthritis,
      and uveitis. It is caused by mutations in the NOD2 gene, also termed the CARD15
      gene. OBJECTIVE: To report a novel mutation in the NOD2 gene associated with Blau
      syndrome. METHODS AND RESULTS: The proband was a 68-year-old ethnic Norwegian
      male who had uveitis and arthritis since 10 years of age followed by lifelong
      recurrent arthritis and chronic eye involvement. Genetic analysis showed a
      heterozygous c.1814 C>A, T605N mutation in NOD2 that has not previously been
      described. All of his three children had Blau syndrome and had inherited the NOD2
      mutation. The proband's first son had exanthema, arthritis, and uveitis from 10
      years of age and later presented with granulomatous lymphadenopathy,
      granulomatous parotitis, and granulomatous intestinal inflammation. The proband's
      daughter had arthritis, uveitis, and exanthema from 3 years of age. The proband's
      second son had uveitis, exanthema, and arthritis from 1.5 years of age. None of
      the cases had any involvement of the heart or lungs. CONCLUSION: We report a
      novel Blau syndrome-associated mutation with an autosomal dominant heritage. Most
      likely the mutation has arisen de novo in the proband. Genetic counselling and
      antenatal diagnostics should be available to the involved families.

PMID- 19169909
TI  - A case of chondrosarcoma-associated polyarthritis.

PMID- 19169911
TI  - Prescribing errors in general practice: a prospective study.
AB  - Prescribing is one of the commonest tasks in daily general practice. Surprisingly
      there is little published research on errors that occur in this area. The aim of
      this study was to estimate the seriousness and level of prescribing errors that
      occurred in general practice. This prospective survey documented errors in
      prescriptions from 28 general practitioners as they occurred over a 3-day period
      in 12 community pharmacies. From a total of 3,948 prescriptions, 491 (12.4%)
      contained one or more errors. From a total of 8,686 drug items, 546 (6.2%)
      contained one or more errors. Of the errors the majority were minor (398, 72.9%),
      a smaller number (135, 24.7%) were major nuisance errors, and there were 13
      (2.4%) potentially serious errors. The most common errors related to drug
      directions and dosage.

PMID- 19169910
TI  - Skin extensibility and consistency in patients with Ehlers-Danlos syndrome and
      benign joint hypermobility syndrome.
AB  - OBJECTIVES: The reproducibility of clinical tests for skin extensibility and
      consistency, essential for differentiating between types of Ehlers-Danlos
      syndrome (EDS) and benign joint hypermobility syndrome (BJHS), is unknown.
      Paraclinical methods may provide objective differential diagnostic methods.
      METHODS: Six EDS, 11 BJHS, and 19 controls completed the trial. We analysed the
      overall inter-examiner agreement on clinical tests for skin extensibility and
      consistency, in addition to analyses on suction cup (SC) and soft tissue
      stiffness meter (STSM) methods. RESULTS: Overall agreement on tests for skin
      extensibility and consistency varied between 0.44 and 0.72. Extensibility
      evaluated by SC showed an insignificant difference between EDS patients and
      controls (p = 0.056). Consistency evaluated by STSM showed significant
      differences (p = 0.001). CONCLUSIONS: Overall inter-examiner agreement on
      clinical tests for skin extensibility and consistency was below 0.80, which was
      required a priori to conduct a reproducibility study. Further refinement of tests
      and a training phase are necessary. The SC and STSM results are encouraging but
      must be reproduced in a larger study population.

PMID- 19169912
TI  - Effectiveness of treating non-specific pruritus vulvae with topical steroids: a
      randomized controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of triamcinolone cream in the treatment
      of non-specific pruritus vulvae. METHODS: A total of 50 patients, aged between 8
      and 55 years, with non-specific pruritus vulvae were consecutively included in a
      double-blind randomized controlled trial by their general practitioner in 25
      general practices in the Netherlands. Analysis was by "intention to treat". An
      infectious cause was excluded by a vaginal and cervical swab. After
      randomization, 27 patients were treated with triamcinolone cream and 23 patients
      with a placebo cream. The effectiveness was assessed by: change in the severity
      of itch visual analogue scale (VAS) score; the percentage of patients with
      complete recovery; and changes in general health according to COOP/WONCA charts.
      RESULTS: The mean decrease in severity of itch was 2.08 points in the
      triamcinolone group compared to 3.26 points in the placebo group. Forty-two per
      cent of the women in the triamcinolone group completely recovered versus 35% in
      the placebo group. There was no difference in general health perception between
      the two groups. After 12 weeks, more than 80% in both groups reported recurrent
      vulval itch. CONCLUSION: No significant differences in effectiveness were found
      between the two groups, because both treatments were ineffective. We can conclude
      that triamcinolone cream is therefore not the treatment of first choice for non
      specific pruritus vulvae.

PMID- 19169913
TI  - Effect of neonatal clomipramine in the pathogenesis of ligature-induced
      periodontitis in Lewis rats.
AB  - OBJECTIVE: The aim of this study was to verify the association between an
      endogenous depression model and the development of ligature-induced periodontitis
      in rats. MATERIAL AND METHODS: Nine male Lewis rats received 30 mg/kg
      clomipramine from neonatal day 8 to day 21 (depressed group), while 13 control
      Lewis rats were left untouched (control group). On day 150, ligatures were placed
      around the 2nd upper molars in both groups, i.e. the contralateral molar of the
      intra-group control. On day 190, the rats were killed and the maxillae were
      defleshed. The distance between the cemento-enamel junction and the alveolar bone
      crest was measured by a blinded examiner using standardized digital photographs.
      RESULTS: The depressed rats showed hyperactivity in open field on day 142 and
      greater attempts to escape on day 143 compared to controls. The other behavioral
      data did not show statistically significant differences between the groups (Mann
      Whitney, p>0.05). In teeth with ligature, mean alveolar bone loss varied from
      0.51 to 0.60 and from 0.63 to 0.64 mm for tests and controls, respectively (t
      test, p>0.05). In teeth without ligature, these values varied from 0.38 to 0.43
      and 0.42 to 0.45 mm in the test and control groups, respectively (t-test,
      p>0.05). CONCLUSION: Induced depression did not alter ligature-induced bone loss
      in Lewis rats.

PMID- 19169914
TI  - Mangafodipir as a cytoprotective adjunct to chemotherapy--a case report.

PMID- 19169915
TI  - A planning comparison of dose patterns in organs at risk and predicted risk for
      radiation induced malignancy in the contralateral breast following radiation
      therapy of primary breast using conventional, IMRT and volumetric modulated arc
      treatment techniques.
AB  - PURPOSE: To investigate the impact of using different radiation therapy
      techniques on contra-lateral breast (CB) dose, and also dose to other involved
      organs at risk such as heart and lungs following radiation therapy of breast and
      regional lymph nodes. Furthermore, to predict the risk for induced malignancies
      in CB using linear and non linear models. MATERIAL AND METHODS: Eight patients
      with stage II-III breast cancer were included in this analysis. It was focused on
      three treatment techniques; conventional radiotherapy technique forwardly planed,
      IMRT and volumetric modulated arc (RapidArc) techniques, inversely planed. The CC
      algorithm was employed to calculate the standard treatment plans whereas for the
      IMRT and RapidArc treatment plans AAA algorithm was adopted. The dose results
      based on mostly DVH analysis were compared. The excess relative risk (ERR) for
      cancer induction in CB, employed both linear and non-linear models, was
      estimated. RESULTS: A better homogeneity and conformation in PTV was observed in
      the RapidArc plans. The highest minimum dose to PTV was observed in the
      conventional plans while no difference was observed for minimum significant doses
      D(98%) and D(99%) where D(X%) is the dose received by X% of the PTV volume. In
      terms of organ sparing, the IMRT and RapidArc plans spare ipsilateral-lung
      better, but a 40% lower mean dose in the contra-lateral lung in the conventional
      plans is observed. The mean dose to the contra-lateral breast was lowest for the
      RapidArc plans as well as the V(10Gy) and the maximum dose. The mean predicted
      ERR for the eight patients were lower for the conventional and RA plans than for
      the IMRT plans assuming a linear dose-risk relationship. The mean predicted ERR
      when using a non linear model was lower for all the three techniques (with lowest
      ERR for RapidArc plans). CONCLUSIONS: From a clinical perspective, it should be
      concluded that all three solutions investigated in the study can offer high
      quality treatment of patients. Further comparative analysis of the two algorithms
      used in the present study, however, should be performed especially on the
      peripheral organ dose. The impact of CB exposure to a low-dose radiation on
      minimizing the risk of radiation induced malignancy in CB can be interpreted
      differently when using linear or non linear models to predict ERR. In general, no
      detriment was observed when using RapidArc compared to conventional treatments
      while a potentially higher risk could be associated to IMRT treatments with fixed
      gantry.

PMID- 19169917
TI  - Minimizing contrast medium doses to diagnose pulmonary embolism with 80-kVp
      multidetector computed tomography in azotemic patients.
AB  - BACKGROUND: In diagnosing acute pulmonary embolism (PE) in azotemic patients,
      scintigraphy and magnetic resonance imaging are frequently inconclusive or not
      available in many hospitals. Computed tomography is readily available, but
      relatively high doses (30-50 g I) of potentially nephrotoxic iodine contrast
      media (CM) are used. PURPOSE: To report on the diagnostic quality and possible
      contrast-induced nephropathy (CIN) after substantially reduced CM doses to
      diagnose PE in azotemic patients using 80-peak kilovoltage (kVp) 16-row
      multidetector computed tomography (MDCT) combined with CM doses tailored to body
      weight, fixed injection duration adapted to scan time, automatic bolus tracking,
      and saline chaser. MATERIAL AND METHODS: Patients with estimated glomerular
      filtration rate (eGFR) <50 ml/min were scheduled to undergo 80-kVp MDCT using 200
      mg I/kg, and those with eGFR >or=50 ml/min, 120-kVp MDCT with 320 mg I/kg. Both
      protocols used an 80-kg maximum dose weight and a fixed 15-s injection time.
      Pulmonary artery density and contrast-to-noise ratio were measured assuming 70
      Hounsfield units (HU) for a fresh clot. CIN was defined as a plasma creatinine
      rise >44.2 micromol/l from baseline. RESULTS: 89/148 patients (63/68 females)
      underwent 80-/120-kVp protocols, respectively, with 95% of the examinations being
      subjectively excellent or adequate. Mean values in the 80-/120-kVp cohorts
      regarding age were 82/65 years, body weight 66/78 kg, effective mAs 277/117, CM
      dose 13/23 g I, pulmonary artery density 359/345 HU, image noise (1 standard
      deviation) 24/21 HU, contrast-to-noise ratio 13/13, and dose-length product
      173/258 mGy x cm. Only 1/65 and 2/119 patients in the 80- and 120-kVp cohorts,
      respectively, with negative CT and no anticoagulation suffered non-fatal
      thromboembolism during 3-month follow-up. No patient developed CIN. CONCLUSION:
      80-kVp 16-row MDCT with optimization of injection parameters may be performed
      with preserved diagnostic quality, using markedly reduced CM doses compared with
      common routine practice, which should be to the benefit of patients at risk of
      CIN.

PMID- 19169918
TI  - Limitations of 64-detector-row computed tomography coronary angiography: calcium
      and motion but not short experience.
AB  - BACKGROUND: Recently, 64-detector-row computed tomography coronary angiography
      (CTA) has been introduced for the noninvasive diagnosis of coronary artery
      disease. PURPOSE: To evaluate the diagnostic capacity and limitations of a newly
      established CTA service. MATERIAL AND METHODS: In 101 outpatients with suspected
      coronary artery disease, 64-detector-row CTA (VCT Lightspeed 64; GE Healthcare,
      Milwaukee, Wisc., USA) was performed before invasive coronary angiography (ICA).
      The presence of >50% diameter coronary stenosis on CTA was rated by two
      radiologists recently trained in CTA, and separately by an experienced colleague.
      Diagnostic performance of CTA was calculated on segment, vessel, and patient
      levels, using ICA as a reference. Segments with a proximal reference diameter <2
      mm or with stents were not analyzed. RESULTS: In 51 of 101 patients and 121 of
      1280 segments, ICA detected coronary stenosis. In 274 of 1280 (21%) segments, CTA
      had non-diagnostic image quality, the main reasons being severe calcifications
      (49%), motion artifacts associated with high or irregular heart rate (45%), and
      low contrast opacification (14%). Significantly more women (43%) had non
      diagnostic scans compared to men (20%). A heart rate above 60 beats per minute
      was associated with significantly more non-diagnostic patients (38% vs. 18%). In
      the 1006 diagnostic segments, CTA had a sensitivity of 78%, specificity of 95%,
      positive predictive value (PPV) of 54%, and negative predictive value (NPV) of
      98% for detecting significant coronary stenosis. In 29 patients, CTA was non
      diagnostic. In the remaining 72 patients, sensitivity was 100%, specificity 65%,
      PPV 79%, and NPV 100%. The use of a more experienced CTA reader did not improve
      diagnostic performance. CONCLUSION: CTA had a very high negative predictive
      value, but the number of non-diagnostic scans was high, especially in women. The
      main limitations were motion artifacts and vessel calcifications, while short
      experience in CTA did not influence the interpretation.

PMID- 19169919
TI  - Effects of pH on nitrite-induced formation of reactive nitrogen oxide species and
      their scavenging by phenolic antioxidants in human oral cavity.
AB  - Nitrite-induced transformation of 3-amino-4-monomethylamino-2',7'
      difluorofluorecein (DAF-FM) to the triazol form (DAF-FMT) was studied using
      bacterial fraction of mixed whole saliva. The transformation at pH 7 was
      inhibited by SCN(-), suggesting that nitrosative stresses were small in the oral
      cavity at the pH value as SCN(-) was a normal component of saliva. DAF-FMT
      formation was much faster at pH 5.2 than 7 and ONSCN generated by the reaction of
      HNO(2) with SCN(-) mainly contributed to its formation at pH 5.2. Coffee and
      phenolic antioxidants inhibited the DAF-FMT formation less effectively at pH 5.2
      than pH 7. The less effectiveness was discussed to be due to slow scavenging of
      ONSCN, which contributed mainly to the formation of DAF-FMT at pH 5.2, by coffee
      and phenolics. Since nitrite-induced formation of ONSCN should become faster as
      the pH decreases, it was suggested that nitrosative stresses to oral tissues
      became serious under acidic conditions.

PMID- 19169920
TI  - Resveratrol treatment protects against doxorubicin-induced cardiotoxicity by
      alleviating oxidative damage.
AB  - The possible protective effects of resveratrol (RVT) against cardiotoxicity were
      investigated in Wistar albino rats treated with saline, saline+doxorubicin (DOX;
      20 mg/kg) or RVT (10 mg/kg)+DOX. Blood pressure and heart rate were recorded on
      the 1st week and on the 7th week, while cardiomyopathy was assessed using
      transthoracic echocardiography before the rats were decapitated. DOX-induced
      cardiotoxicity resulted in decreased blood pressure and heart rate, but lactate
      dehydrogenase, creatine phosphokinase, total cholesterol, triglyceride, aspartate
      aminotransferase and 8-OHdG levels were increased in plasma. Moreover, DOX caused
      a significant decrease in plasma total antioxidant capacity along with a
      reduction in cardiac superoxide dismutase, catalase and Na+,K+-ATPase activities
      and glutathione contents, while malondialdehyde, myelopreoxidase activity and the
      generation of reactive oxygen species were increased in the cardiac tissue. On
      the other hand, RVT markedly ameliorated the severity of cardiac dysfunction,
      while all oxidant responses were prevented; implicating that RVT may be of
      therapeutic use in preventing oxidative stress due to DOX toxicity.

PMID- 19169921
TI  - Studies on paclitaxel-loaded glyceryl monostearate nanoparticles.
AB  - Solid lipid nanoparticles (SLNs) of Paclitaxel were prepared by modified Hot
      homogenization method using Glyceryl monostearate (GMS). The SLNs were
      characterized for its physicochemical characteristics such as mean particle size,
      percentage entrapment efficiency and zeta potential, which were found to be 226
      nm, 92.43% and -29.4 mV, respectively. The Transmission Electron Microscopy (TEM)
      studies showed that prepared SLNs were of spherical shape. The drug retarding
      efficiency of the lipid (GMS) was better in pH 7.4 compared to pH 3.5. The
      release profile showed a tendency to follow Higuchi diffusion pattern at pH 7.4
      and Peppas-Korsenmeyer model at pH 3.5. Chemosensitivity assay carried out using
      B16F10 cell lines showed that anti-proliferative activity of Paclitaxel was not
      hindered due to encapsulation.

PMID- 19169922
TI  - Genetic analysis of chaste, a new mutation of Drosophila melanogaster
      characterized by extremely low female sexual receptivity.
AB  - By screening about 2,000 P-element-insertion lines of Drosophila melanogaster, we
      isolated a new behavioral mutant line, chaste (chst), the females of which
      display extraordinarily strong rejection behavior against courting males. The
      chst mutation is mapped to the muscleblind (mbl) locus at 54B on the right arm of
      chromosome 2. The reduced sexual receptivity in chst mutant females is reversed
      to the wild-type level by introducing a transgene, which expresses either the
      mblB (+) or mblC (+) isoform, demonstrating that chst is an allele of mbl. Among
      the P-elements inserted upstream of the mbl gene, those inserted in the same
      orientation as that of mbl express the chst phenotype, whereas a P-element
      inserted in the opposite orientation does not. This finding implies that the
      former P-elements induce the mutant phenotype by a mechanism that is sensitive to
      the direction of transcription (e.g., transcriptional interference). The mbl
      alleles, with deletions near the transcription start site and/or in part of the
      exons, complement the chst mutation in the sexual receptivity phenotype, but not
      in the lethality phenotype of mbl mutations. Such interallelic complementation of
      the sexual receptivity phenotype in the mbl locus disappears in the presence of a
      mutant copy of zeste (z), a gene encoding a protein that mediates transvection.
      We suggest that the mbl gene function is required for the normal development of
      neural substrates that regulate female sexual receptivity.

PMID- 19169924
TI  - Attachment orientations and daily condom use in dating relationships.
AB  - This daily experience study examined the roles of attachment orientations and
      daily relationship satisfaction in shaping daily condom use among college
      students in dating relationships. Seventy-five participants completed an initial
      measure of attachment orientation and then reported their relationship
      satisfaction and condom use each day for 14 consecutive days. The results showed
      that attachment anxiety was associated with less frequent use of condoms on a
      daily basis. Daily satisfaction was also associated with a decreased likelihood
      of using condoms, and this association was stronger for those high in attachment
      anxiety and mitigated for participants high in attachment avoidance. The
      associations between attachment orientations and daily condom use remained
      significant when controlling for important covariates including participant
      gender, use of another form of birth control, frequency of sex, and knowledge of
      a partner's sexual history. Implications for sexual risk-taking behaviors and
      future research using daily diary methods to study sexuality in intimate
      relationships are discussed.

PMID- 19169925
TI  - An investigation of increases in metamemory confidence across multiple study
      trials.
AB  - We employed a list-learning methodology to investigate whether discrepancies
      between mean judgements of learning (JOLs) and recall in a multiple study-recall
      context reflects a metacognitive failure in applying the knowledge that repeated
      study benefits recall. In Experiment 1 one group of participants was explicitly
      informed that repetition enhances recall, whereas a second group was told that
      repetition was not beneficial for future recall. Although JOLs in the former
      condition were significantly higher, this difference was evident even in the
      first study phase, prior to any repetition taking place. In Experiment 2 we
      investigated whether the modest increases in JOLs that are typically observed
      over multiple study trials reflects instead an attribution of enhanced fluency,
      rather than metacognitive understanding per se.

PMID- 19169923
TI  - Nicotine dependence pharmacogenetics: role of genetic variation in nicotine
      metabolizing enzymes.
AB  - Nicotine-dependence pharmacogenetics research is an emerging field, and a number
      of studies have begun to characterize the clinical relevance and predictive power
      of genetic variation in drug-metabolizing enzymes and drug target genes for
      response to medication. The present paper focuses on evidence for the role of
      nicotine-metabolizing enzymes in smoking behavior and response to treatment.
      Nicotine metabolism is mediated primarily by cytochrome P450 2A6 (CYP2A6).
      Genetic variation in the CYP2A6 gene has been linked with several smoking
      behavior phenotypes. Individuals who carry null or reduced activity alleles for
      CYP2A6 smoke fewer cigarettes per day, are less dependent on nicotine, and may
      have an easier time quitting smoking. A phenotypic measure of CYP2A6 enzyme
      activity, defined as the ratio of the nicotine metabolites
      3'hydroxycotinine/cotinine, also predicts successful quitting with the
      transdermal nicotine patch, and counseling alone. Faster metabolizers of nicotine
      respond more poorly to these treatments; however, they may be excellent
      candidates for non-nicotine therapies, such as bupropion. Inherited variation in
      the CYP2B6 enzyme is also associated with response to bupropion treatment and
      counseling alone for smoking cessation. Inhibition of the CYP2A6 enzyme to slow
      nicotine metabolism is a promising approach to increase nicotine availability and
      potentially reduce harm from tobacco smoking.

PMID- 19169926
TI  - Subliminal priming of autobiographical memories.
AB  - The current research examined subliminal priming of autobiographical memories. In
      Experiment 1 the subliminal primes consisted of affect-associated words (positive
      vs negative) and were presented just before the participants retrieved specific
      experiences to cue-words. The subliminal primes produced an inhibitory effect on
      autobiographical memory retrieval, with significantly lower positive ratings
      given to the emotional content of experiences retrieved after positive primes
      than given to experiences retrieved after negative primes. The subliminal primes
      for the second experiment consisted of words that related to specific lifetime
      periods (early childhood vs late childhood/early adulthood). A negative priming
      effect resulted again, with earlier life experiences retrieved after the
      presentation of late childhood/early adulthood primes. We believe the negative
      priming effects obtained in both experiments are consistent with predictions
      based on the self-memory system model of autobiographical memory. The results of
      this research may also explain mood-incongruent recall.

PMID- 19169927
TI  - Vitamin A and cervical squamous intraepithelial lesions.

PMID- 19169928
TI  - Running along.

PMID- 19169929
TI  - Prognostic significance of the interaction between abnormal umbilical and middle
      cerebral artery Doppler velocimetry in pregnancies complicated by fetal growth
      restriction.
AB  - OBJECTIVE: To evaluate the prognostic significance of the interaction between
      umbilical artery (UA) and middle cerebral artery (MCA) Doppler measurements in
      pregnancies complicated by fetal growth restriction (FGR). DESIGN: Cohort study.
      SETTING: Third-level Perinatology Center in Northern Italy. POPULATION: A study
      of 184 singleton pregnancies at 24-35 weeks' gestational age complicated by FGR
      and abnormal UA Doppler measurements. METHODS: FGR was diagnosed by serial
      ultrasonograms. Neonatal brain damage was defined as the presence of cystic
      leukomalacia or grade III-IV intraventricular hemorrhage. MAIN OUTCOME MEASURES:
      Perinatal death and neonatal brain damage. RESULTS: The prevalence of
      fetal/neonatal death or brain damage was 18.2% (16/88) in pregnancies with UA
      absent/reversed diastolic flow and 4.2% (4/96) in those with increased UA Doppler
      pulsatility. Stepwise logistic regression identified decreasing gestational age
      (OR=1.75, 95% confidence interval, CI=1.35-2.22) and absent/reversed UA blood
      flow (OR=3.34, 95% CI=1.1-10.9) as predictors of fetal/neonatal death or brain
      damage. A MCA pulsatility index below the 10th percentile was a risk factor for
      fetal/neonatal death or brain damage among women with absent/reversed UA
      diastolic flow (14/53 as compared to 2/35; OR=5.9, CI =1.4-40.3) but not in
      pregnancies with forward velocity (1/33 as compared to 3/63; OR=0.63, 95% CI=0.02
      6.13, Synergy index=27.7, p=0.007). CONCLUSIONS: In pregnancies complicated by
      FGR and absent/reversed UA end diastolic flow, vasodilatation of the MCA is a
      risk factor for neonatal death or brain damage.

PMID- 19169930
TI  - Discontinuation of oxytocin in the active phase of labor.
AB  - OBJECTIVE: To show that early discontinuation of oxytocin will not increase the
      mean duration of the active labor phase in a clinically significant way. DESIGN:
      Controlled non-inferiority study. SETTING: Department of Obstetrics and
      Gynecology, University of Caen, Clemenceau Hospital, France. POPULATION: A total
      of 138 women with singleton pregnancy and a vertex presentation of over 34
      gestational weeks, presenting a medical indication of induction of labor or a
      dystocia at onset of labor, from May 2005 to June 2006. METHODS: Two parallel
      groups were compared: continuation of oxytocin until delivery versus
      discontinuation of oxytocin at the onset of the active phase. The clinically
      acceptable increase in mean duration of the active phase of labor (non
      inferiority margin) was set at 60 minutes. MAIN OUTCOME MEASURES: Primary outcome
      measure was duration of the active labor phase. Secondary outcome measures
      included total duration of labor, parameters concerning oxytocin use, rates of
      uterine hyperstimulation and fetal heart rate (FHR) abnormalities, and mode of
      delivery. Some neonatal outcomes were also analyzed. RESULTS: Equivalence of the
      two strategies (continuation vs. discontinuation of oxytocin) was not
      demonstrated (p=0.97 testing for non-inferiority), the active phase even being
      significantly longer by a mean of 113 minutes (p=0.0001 testing for superiority).
      The rates of cesarean sections, alterations of FHR and delivery hemorrhage were
      higher when oxytocin was continued, but not significantly. There were
      significantly more infants hospitalized in neonatology when oxytocin was
      continued (p=0.028). CONCLUSIONS: Discontinuation of oxytocin at the onset of the
      active phase prolongs labor. We found no argument for discontinuing the infusion
      of oxytocin at the onset of the active phase.

PMID- 19169931
TI  - Activated nuclear factor-kappaB and increased tumor necrosis factor-alpha in
      atrial tissue of atrial fibrillation.
AB  - OBJECTIVES: To depict the interaction between atrial fibrillation (AF) and
      inflammatory reaction, studies were taken to measure the activity of NF-kappaB in
      myocardium, the concentration of regional inflammatory factors and the
      pathological process of the right atrium in patients with AF. DESIGN: Patients
      with valvular disease with AF or sinus rhythm (SR) were recruited and compared.
      Before the extracorporal circulation, about 250 mg tissue of right atrium was
      collected for pathological examination. The activity of NF-kappaB in myocardium
      was measured by electrophoretic mobility shift assay (EMSA), and the
      concentration of cardiac tissue interleukin-6 (IL-6) and tumor necrosis factor
      (TNF-alpha) was determined by radioimmuoassay. RESULTS: Patients with valvular
      disease with AF exhibited higher NF-kappaB activity, higher concentration of TNF
      alpha and IL-6, severe lymphomonocyte infiltration, and more fibrosis than those
      patients with valvular disease with SR. There were significant positive
      correlations among NF-kappaB activity and levels of TNF-alpha and IL-6 and
      collagen volume fraction. CONCLUSIONS: This study proved the presence of
      inflammation in atrial myocardium by triggering inflammatory reaction.

PMID- 19169932
TI  - Circulatory assistance in acute heart failure--where do we go from here?
AB  - The comment concerns two short-term assist systems, namely the Impella axial-flow
      recovery system and extra-corporeal membrane oxygenation (ECMO) used for
      circulatory assistance in patients with acute heart failure. The results,
      particularly for patients in cardiogenic shock not related to cardiac surgery,
      calls for cautious optimism.

PMID- 19169933
TI  - A new healthcare act in process in Finland.

PMID- 19169934
TI  - Palmitoylation cycles and regulation of protein function (Review).
AB  - The efficacy and success of many cellular processes is dependent on a tight
      orchestration of proteins trafficking to and from their site(s) of action in a
      time-controlled fashion. Recently, a dynamic cycle of palmitoylation/de
      palmitoylation has been shown to regulate shuttling of several proteins,
      including the small GTPases H-Ras and N-Ras, and the GABA-synthesizing enzyme
      GAD65, between the Golgi compartment and either the plasma membrane or synaptic
      vesicle membranes. These proteins are peripheral membrane proteins that in the
      depalmitoylated state cycle rapidly on and off the cytosolic face of ER/Golgi
      membranes. Palmitoylation of one or more cysteines, by a Golgi localized
      palmitoyl transferase (PAT) results in trapping in Golgi membranes, and sorting
      to a vesicular pathway in route to the plasma membrane or synaptic vesicles. A
      depalmitoylation step by an acyl protein thioesterase (APT) releases the protein
      from membranes in the periphery of the cell resulting in retrograde trafficking
      back to Golgi membranes by a non-vesicular pathway. The proteins can then enter a
      new cycle of palmitoylation and depalmitoylation. This inter-compartmental
      trafficking is orders of magnitude faster than vesicular trafficking. Recent
      advances in identifying a large family of PATs, their protein substrates, and
      single PAT mutants with severe phenotypes, reveal their critical importance in
      development, synaptic transmission, and regulation of signaling cascades. The
      emerging knowledge of enzymes involved in adding and removing palmitate is that
      they provide an intricate regulatory network involved in timing of protein
      function and transport that responds to intracellular and extracellular signals.

PMID- 19169935
TI  - Acyltransferases for secreted signalling proteins (Review).
AB  - Members of the MBOAT family of multispanning transmembrane enzymes catalyze the
      acylation of important secreted signalling proteins of the Hedgehog, Wg/Wnt and
      ghrelin families. Acylation of these substrates occurs during transport through
      the secretory pathway and plays key roles in their biological activity and spread
      from producing cells, contributing to the formation of appropriate extracellular
      concentration gradients. Characterization of these enzymes could lead to their
      identification as therapeutic targets for diverse human diseases such as cancers,
      obesity and diabetes.

PMID- 19169936
TI  - Behavioural assessment of the Dysexecutive Syndrome for Children (BADS-C): an
      examination of construct validity.
AB  - Children's success with participating in life depends heavily on intact executive
      function (EF) skills. The Behavioural Assessment of the Dysexecutive Syndrome for
      Children (BADS-C) was developed to address the need for a standardised
      ecologically valid test of children's EF performance. This study aimed to
      establish the construct validity of the BADS-C in relation to socio-demographic
      parameters. Participants were 208 Israeli children, aged 8-15 years, who were
      divided into three age groups (8 years to 9 years and 11 months; 10 years to 11
      years and 11 months; 12 to 15 years) and tested with the BADS-C. The older age
      groups achieved significantly better scores than the younger groups. No
      significant differences were found between genders in any of the BADS-C scores.
      Similar results were found for familial socio-economic status and parents'
      education. Construct validity was demonstrated for the BADS-C by providing a
      profile for different age groups. Additional studies are needed to examine
      further the validity and reliability of the BADS-C and the relationships between
      socio-demographic factors and EF.

PMID- 19169937
TI  - Trends of tuberculin skin test positivity rate among schoolchildren in Attica,
      Greece.
AB  - We sought to estimate the prevalence and temporal trends of tuberculin skin test
      (TST) positivity rate among schoolchildren, in a suburban area of Attica, Greece.
      We retrospectively analysed the prevalence of the TST positivity (forearm volar
      surface induration >10 mm) of schoolchildren, in the catchment area of the public
      primary healthcare centre of Vari, over a 16-y period (1990-2005). TSTs were
      performed in the context of a national, government-directed TB screening
      programme. We retrieved 11,105 records of TSTs performed on children aged 6 and
      14 y. These tests referred to 7920 and 2969 BCG unvaccinated and vaccinated
      children, respectively, as well as 120 children who had close contact with a TB
      confirmed case, and 6 children with known active or latent TB. The prevalence of
      TST positivity among BCG unvaccinated children was 2.0% over the whole study
      period; this figure declined in the second compared to the first half of the
      study period (2.4% vs 1.4%, p<0.001). The gradual decline in TST positivity among
      BCG unvaccinated schoolchildren, despite the substantial rise in the number of
      immigrants in Greece, over our study period, may, at least in part, be attributed
      to relevant national screening and prevention measures.

PMID- 19169938
TI  - Awareness of expressivity deficits in non-demented Parkinson disease.
AB  - A masked facial expression, one of the hallmark features of Parkinson disease
      (PD), can form the basis for misattributions by others about a patient's mood or
      interest levels. Reports of preserved intensity of internal emotional experience
      in PD participants raise the question of whether patients are aware of their
      outward expressivity levels. The aim of the present study was to determine
      whether PD participants exhibit deficits in overall emotional expressivity, and
      if so, whether they are aware of these deficits. We evaluated 37 non-demented PD
      participants and 21 comparison participants using the Berkeley Expressivity
      Questionnaire (BEQ). To examine awareness of emotional expressivity, we compared
      participant self-ratings of their own expressivity to ratings made by family
      members or close friends. Participants also completed questionnaires regarding
      depression and apathy and underwent motor examination and cognitive screening. PD
      participants' self-ratings of emotional expressivity were significantly lower
      than comparison participants' self-ratings. Even so, the PD participants viewed
      themselves as experiencing equivalent levels of emotional intensity to comparison
      participants, based on analysis of the BEQ subscales. Informant and PD
      participant self-ratings did not differ, indicating that PD participants
      accurately appraise the extent of their reduced expressivity. These findings
      suggest that anosognosia for emotional expressivity is not a prominent feature of
      nondemented Parkinson disease. Importantly, PD participants are aware of their
      reduced expressivity and report experiencing emotions as intensely as comparison
      participants. These findings highlight the view that diminished emotional
      expressivity in PD should not be mistaken for decreased subjective emotional
      experience.

PMID- 19169941
TI  - Monolithic osmotic tablet containing solid dispersion of 10-hydroxycamptothecin.
AB  - A novel monolithic osmotic tablet composed of solid dispersion of water-insoluble
      10-hydroxycamptothecin (HCPT) was prepared. The tablet core was made of a
      suspending agent, polyethylene oxide, an osmotic agent, sodium chloride, and a
      solid dispersion consisting of polyethylene glycol 6000 and HCPT. Optimized
      formulation was able to deliver HCPT at the constant rate of 1.21 mg/hour for 12
      hours with cumulative release above 90% in vitro, independent of environmental
      media and stirring rate, and the release rate is co-controlled by osmotic
      pressure, suspending effect, and drug solubility in solid dispersion. The
      monolithic osmotic tablet containing solid dispersion has great potential in the
      controlled delivery of water-insoluble drugs.

PMID- 19169942
TI  - Step nonisothermal method to study stability of drugs.
AB  - A step nonisothermal experiment under high oxygen pressure and a new computation
      with optimization for step nonisothermal experiment on stability study of drugs
      was introduced. The kinetics parameters of captopril oxidation in aqueous
      solution were determined by this method. It is reported that the reaction of
      captopril solution occurs under either aerobic or anaerobic condition, giving
      different products. Then the total rate constant k(total) can be expressed as
      [image omitted] where k(anaerobic) and k(aerobic) are the rate constants of
      anaerobic and aerobic degradations, respectively. The results indicated that the
      parameters obtained in the step nonisothermal experiment were comparable with
      those obtained in the isothermal-isobaric experiments. By a computer simulation,
      the estimates for the kinetic parameters (E(a) and k(0)) obtained with step
      nonisothermal method were statistically evaluated. Results indicated that the
      estimates obtained with isothermal-isobaric method were somewhat more precise
      than those obtained with step nonisothermal method. However, the experimental
      period needed by isothermal-isobaric method was much longer than that needed by
      step nonisothermal method.

PMID- 19169943
TI  - Development of alpha-tocopherol acetate nanoparticles: influence of preparative
      processes.
AB  - We studied different methods of preparing alpha-tocopherol acetate (ATA)
      nanoparticles, which are to be used in targeting the lungs as aerosols in order
      to prevent cigarette smoke toxicity. Poly-(lactide) nanoparticles were prepared
      using nanoprecipitation and solvent evaporation techniques, which produced,
      respectively, too small and too large nanoparticles to be aerosolized. The
      emulsification-diffusion method produced 2 months stable nanoparticles with a
      size between (500-700 nm). Increasing ATA concentration (1-7 mg/mL) induced a
      decrease in the association rate (97-93%) and in the adsorbed ATA rate (7-4.5%),
      which was associated with variations of Zeta potentials (-27.5 to -24.3 mV) and
      decrease in polymeric wall thickness and density.

PMID- 19169944
TI  - An investigation on sources of potential minerals found in traditional vegetables
      of north-east India.
AB  - The north-eastern region of India is endowed with a great wealth of plant genetic
      resources. Out of the vast floral diversity of the region, a large number of
      indigenous plant species and their wild forms constitute the routine vegetables
      of the inhabitants, which provide sufficient nutrients and medicinal values for
      the people. They seem to be quite healthy on average, even though the ethnic
      tribes are ignorant about the concept of balanced diet and healthcare. This paper
      describes the mineral (calcium, magnesium, iron, potassium and phosphorus)
      contents and chemical composition in percentages such as carbohydrate, protein,
      fat, and so forth, found in 15 traditional vegetable species collected from
      different parts of North-east India. The results of this study contribute to the
      knowledge on vitamin contents in these vegetables. The amounts of ascorbic acid
      found in some species were much higher than the amount present in many
      conventional vegetables.

PMID- 19169946
TI  - Glycaemic index of some commercially available rice and rice products in Great
      Britain.
AB  - The glycaemic response to nine types of rice (white basmati, brown basmati, white
      and brown basmati, easy-cook basmati, basmati and wild rice, long-grain rice,
      easy-cook long-grain rice, Thai red rice, Thai glutinous rice) and two types of
      rice vermicelli (Guilin rice vermicelli, Jiangxi rice vermicelli) commercially
      available in the United Kingdom were compared against a glucose standard in a non
      blind, randomized, repeated-measure, crossover design trial. Fourteen healthy
      subjects (six males, eight females), mean age 38 (standard deviation 16) years
      and mean body mass index 21.3 (standard deviation 2.3) kg/m(2), were recruited
      for the study. Subjects were served portions of the test foods and a standard
      food (glucose), on separate occasions, each containing 50 g available
      carbohydrates. Capillary blood glucose was measured from finger-prick samples in
      fasted subjects (-5 and 0 min) and at 15, 30, 45, 60, 90 and 120 min after the
      consumption of each test food. For each type of food, its glycaemic index (GI)
      was calculated geometrically by expressing the incremental area under the blood
      glucose curve as a percentage of each subject's average incremental area under
      the blood glucose curve for the standard food. The 10 foods exhibited a range of
      GI values from 37 to 92. The study indicated that rice noodles, long-grain rice,
      easy-cook long-grain rice and white basmati rice were low-GI foods, whilst all of
      the other foods were medium-GI and high-GI foods. The information presented in
      this paper may be useful in helping people select low-GI foods from the customary
      foods consumed by the British and Asian populations.

PMID- 19169947
TI  - Drosophila neurogenetics--the Heisenberg impact.

PMID- 19169948
TI  - Fatal Trichoderma harzianum infection in a leukemic pediatric patient.
AB  - We report the repeated isolation for Trichoderma.harzianum, a rare opportunistic
      pathogen from three sets of each of the following clinical samples; blood serum,
      skin lesions, sputum and throat of a pediatric ALL patient with neutropenia. The
      definition of invasive fungal infection requires evidence of the presence of
      fungal elements in tissue samples, in addition to the isolation of suspected
      etiologic agent in culture. However, invasive procedures are not always
      applicable due to several factors, as for example in our case, the poor general
      status of the individual patient or thrombocytopenia. The present paper also
      emphasizes the problems encountered in obtaining appropriate samples and
      diagnosing invasive fungal disease in immunocompromised patient populations,
      including those with hematological malignancy. Three cases involving T.
      harzianum, including this one, have been described thus far in the literature.
      All were fatal and the fungus was resistant to antifungal therapy. A critical
      review of the other two cases of Trichoderma infections in humans is provided.

PMID- 19169949
TI  - Disseminated Geosmithia argillacea infection in a German shepherd dog.
AB  - We report a systemic mycosis in a German Shepherd dog caused by Geosmithia
      argillacea. Although this etiologic agent microscopically resembles a Penicillium
      species, and is histopathologically compatible with members of the genus
      Aspergillus, morphologic features and molecular characterization clearly separate
      it from these genera. This appears to be the first report of disseminated disease
      by this species in humans or animals. In vitro antifungal susceptibility testing
      suggests resistance to amphotericin B and voriconazole and susceptibility to
      caspofungin, itraconazole, and posaconazole.

PMID- 19169950
TI  - Herbal plants as a promising source of natural antifoulants: evidence from
      barnacle settlement inhibition.
AB  - A series comprising hexane, ethyl acetate, ethanol and aqueous extracts from six
      common Chinese herbs (Carpesium abrotanoides, Melia toosendan, Cnidium monnieri,
      Vitex negundo, Stemona sp. and Sophora flavescens) was investigated for
      antifouling (AF) activity against cypris (cyprids) larvae of the barnacle Balanus
      albicostatus. All extracts tested except the aqueous extract from Stemona sp.
      significantly inhibited the settlement of cyprids, the most potent being the
      ethyl acetate extract of S. flavescens (EC(50) value 2.08 microg ml(-1)), from
      which an AF compound, identified as 2'-methoxykurarinone, was isolated using
      bioassay-guided procedures. Furthermore, the AF activity of this compound was
      found to be highly reversible and greater than that of the three other natural
      products from S. flavescens, namely matrine, oxymatrine and oxysophocarpine.
      These compounds have been used commercially in China for their pharmaceutical
      activities, but their AF activities have not previously been evaluated. Analysis
      of structure-activity relationships suggested that the N-1 nitrogen atom in
      matrine plays a crucial role in AF activity. Overall, the present findings
      indicate that herbal plants are a valuable source of novel AF agents.

PMID- 19169951
TI  - Cathodic behaviour of stainless steel in coastal Indian seawater: calcareous
      deposits overwhelm biofilms.
AB  - Type-316 stainless steel (SS) was investigated as the cathode in galvanic couples
      in full-strength seawater from the Gulf of Mannar on the southeast coast of
      India. Tests were devised to examine the impact of SS cathodes on anode materials
      with or without the accrual of marine biofilms. Biofilmed SS cathodes
      significantly enhanced the rate of corrosion of nickel, causing noble shifts in
      the couple potentials. With mild steel and zinc as the anodes, calcareous
      deposits developed quite rapidly on the SS cathodes and led to a significant
      reduction of bacterial numbers. The calcareous deposits also caused substantial
      reduction of galvanic corrosion rates for mild steel, whereas there was no
      difference for zinc. The deposits were identified by XRD as essentially
      carbonates, oxides and hydroxides of calcium and magnesium. Potentiodynamic
      polarization performed on the actual couples after disconnection and
      equilibration provided reasonable interpretations of the galvanic corrosion
      trends. Data from this work suggest that a potential of about -0.70 V vs.
      saturated calomel electrode (SCE) should provide optimum protection of SS in
      warmer, full-strength seawater that supports the precipitation of calcareous
      deposits. The criterion commonly recommended for temperate conditions of lower
      water temperature and estuarine waters of lower alkalinity is -1.0 V (SCE).

PMID- 19169952
TI  - Antennular sensory organs in cyprids of balanomorphan cirripedes: standardizing
      terminology using Megabalanus rosa.
AB  - Cirripedes are one of the major groups of fouling organism in the marine
      environment. The cyprid can, before a permanent attachment, actively explore and
      walk on the substratum using its antennules in a bipedal fashion without leaving
      the surface. Studying the structure of the cyprid antennule is therefore
      important for understanding the events that culminate in biofouling by barnacles.
      There are at present no complete, standardised accounts of the structure of the
      cyprid antennules in thoracican barnacles, and moreover, the existing accounts
      vary in their use of terminology. This article describes the cyprid antennule of
      the barnacle Megabalanus rosa. This barnacle species is common in E Asia, and the
      cyprids have previously been used in several biofouling studies. All externally
      visible setae on the antennules have been mapped; these comprise both
      chemosensors with a terminal pore, a putative aesthetasc-like seta and mechano
      sensory setae. More setae were found on the attachment disc than in previous
      scanning electron microscope-based studies, but not all structures that can be
      seen with transmission electron microscopy were visible. The disc itself seems to
      have a variable surface area, which could assist in exploring rough surfaces. The
      various lengths of the antennular setae, coupled with the disposition of the
      segments, enable the cyprid to cover a wide swath of substratum during
      exploratory walking. A new terminology is proposed for cyprid antennular setae,
      which will form a basis for future comparative and functional studies of
      cirripede settlement.

PMID- 19169953
TI  - The effect of surface colour on the adhesion strength of Elminius modestus Darwin
      on a commercial non-biocidal antifouling coating at two locations in the UK.
AB  - A number of factors affect the adhesion strength of organisms to fouling-release
      coatings, and except for a few studies focussing on black or white surfaces none
      have dealt specifically with the effect of coating colour. The aim was to test
      the effect of colour on the adhesion strength of the barnacle Elminius modestus.
      Panels coated in six commercial colours of Intersleek 700 were submerged at two
      field sites and barnacles were pushed-off using a standard assay procedure. The
      strength of adhesion (SOA) varied between and within sites for colour and by
      barnacle basal area, SOA per unit area being higher for smaller barnacles. Higher
      SOA with a small basal area may be because of size-specific predation,
      differential hydrodynamic effects or adhesive failure with age. The complex
      effect of colour on barnacle adhesion may be because of physico-chemical surface
      characteristics varying with pigments, and their interactions with local
      environmental conditions, as well as interactions with the settling barnacle
      larvae.

PMID- 19169954
TI  - Turning lemons into lemonade: learning from negative studies in cancer
      immunotherapy.

PMID- 19169955
TI  - Diplomatic immunity: turning a foe into an ally.
AB  - Striking a balance between subversion of antiviral immune responses and
      enhancement of potentially therapeutic, antitumor cytotoxic responses is a
      challenge at the forefront of oncolytic virus (OV) research. Some of the immune
      hurdles that must be overcome to maximize OV delivery to spread throughout tumor
      beds, and an outline of some of the strategies developed to deal with these
      obstacles are reviewed. In addition, current research that may lead to antitumor
      immunity during, or subsequent to, OV therapy is discussed. Finally speculations
      are made upon emerging areas of viral and immune research that could be merged to
      create new therapeutic paradigms.

PMID- 19169956
TI  - BiTE: Teaching antibodies to engage T-cells for cancer therapy.
AB  - Bispecific T-cell-engager (BiTE) antibodies are designed to transiently engage
      cytotoxic T-cells for lysis of selected target cells. Although this therapeutic
      concept had been proposed more than two decades ago, BiTE, and also trispecific,
      antibodies did not achieve clinical proof-of-concept until the past 2 years.
      Their clinical activity corroborates findings that ex vivo expanded, autologous T
      cells derived from tumor tissue, or transfected with specific T-cell receptors,
      have shown therapeutic potential in the treatment of solid tumors. While these
      personalized approaches prove that T-cells alone can have considerable
      therapeutic activity, even in late-stage cancer, they are cumbersome to perform
      on a broad basis. This is different for cytotoxic T-lymphocyte antigen 4 (CTLA-4)
      antibodies, which facilitate generation of tumor-specific T-cell clones, and also
      for bi- and tri-specific antibodies that directly engage a large proportion of
      patients' T-cells for cancer cell lysis. The potential of global T-cell
      engagement for human cancer therapy by T-cell-engaging antibodies has yet to be
      fully investigated.

PMID- 19169957
TI  - Cancer vaccines: current directions and perspectives in prostate cancer.
AB  - Numerous research groups are investigating the use of cancer vaccines as a
      potential therapeutic modality for various tumor types. The efficacy of cancer
      vaccines has improved because of advances in the characterization of tumor
      associated antigens, the development of improved vaccine delivery systems, and
      the combination of vaccines with cytokines and other immunostimulants to enhance
      immune responses. Although cancer vaccines are under investigation for the
      treatment of various different tumor types, several characteristics of prostate
      cancer make it an ideal target for immunotherapy. The relative indolence of
      prostrate cancer allows sufficient time to generate immune responses, which
      usually take weeks or months to mount. In addition, prostate cancer-associated
      antigens direct the immune response to prostate cancer cells, thus sparing normal
      tissue. This review focuses on promising new strategies for combining vaccines
      with other therapeutic approaches, as well as novel perspectives in the treatment
      of prostate cancer.

PMID- 19169958
TI  - Combining radiation and immunotherapy for synergistic antitumor therapy.
AB  - The combination of radiation therapy and immunotherapy holds enticing promise as
      a strategy for cancer treatment. Preclinical studies have shown that radiation
      may act synergistically with immunotherapy to enhance or broaden antitumor immune
      responses, in part, because of radiation-induced phenotypic alterations of tumor
      cells that render them more susceptible to immune-mediated killing. Clinical
      trials utilizing the combination of therapeutic vaccines with radiation have
      supported many of these findings, and other clinical trials are both ongoing and
      planned. This review examines the evidence that radiation induces immunological
      death, the mechanisms by which radiation therapy can induce or augment antitumor
      immune responses, and translational studies demonstrating that immunotherapy can
      be effectively combined with radiation therapy. Finally, recent and current
      clinical trials combining radiation therapy with immunotherapy are reviewed.

PMID- 19169959
TI  - Clinical testing of engineered oncolytic measles virus strains in the treatment
      of cancer: an overview.
AB  - Viruses have adapted through millennia of evolution to effectively invade and
      lyse cells through diverse mechanisms. Strains of the attenuated measles virus
      Edmonston (MV-Edm) vaccine lineage can preferentially infect and destroy
      cancerous cells while sparing the surrounding tissues. This specificity is
      predominantly due to overexpression of the measles virus receptor CD46 in tumor
      cells. To facilitate in vivo monitoring of viral gene expression and replication,
      these oncolytic strains have been engineered to either express soluble marker
      peptides, such as the human carcinoembryonic antigen (CEA; MV-CEA virus), or
      genes that facilitate imaging and therapy, such as the human thyroidal sodium
      iodide symporter (NIS) gene (MV-NIS). Preclinical efficacy and safety data for
      engineered oncolytic MV-Edm derivatives that led to their clinical translation
      are discussed in this review, and an overview of the early experience in three
      ongoing clinical trials of patients with ovarian cancer, glioblastoma multiforme
      and multiple myeloma is provided. The information obtained from these ongoing
      trials will guide the future clinical application and further development of MV
      strains as anticancer agents.

PMID- 19169960
TI  - A review of contusugene ladenovec (Advexin) p53 therapy.
AB  - Contusugene ladenovec (Advexin; INGN-201; Introgen Therapeutics Inc) is a
      replication-impaired, non-integrating, serotype 5 adenoviral vector that carries
      the p53 gene under the control of the CMV promoter. Deletion or mutation of the
      p53 gene has been observed in approximately half of malignancies in patients with
      cancer and p53 pathway dysfunction was observed in the majority of others,
      thereby providing the rationale for p53 restoration in the treatment of cancer.
      Advexin has demonstrated a consistent safety profile and clinical efficacy as a
      monotherapy, as well as in combined modality regimens with chemotherapy and
      radiation. Additive or synergistic effects have been observed in a variety of
      tumor types, including NSCLC, squamous cell carcinoma of the head and neck,
      hepatocellular carcinoma, glioma, and breast, prostate and colorectal cancers.
      The identification of biomarkers may help direct research in tumor-specific
      therapeutics.

PMID- 19169961
TI  - Hsp receptors: the cases of identity and mistaken identity.
AB  - Immune responses elicited by Hsps have been harnessed for the therapy of cancer.
      Hsps may also play a physiological role in the transfer of antigens in the form
      of peptides between cells during the event known as cross priming. To elicit
      these immune responses, Hsps engage antigen-presenting cells through their cell
      surface receptors. Various molecules have been suggested as Hsp receptors since
      their existence was first proposed 13 years ago. This review critically examines
      the literature on Hsp receptors and highlights the experimental evidence that has
      been provided or is lacking for each molecule. Two phase III clinical trials
      conducted with Hsp-based vaccines in patients with melanoma or renal cell
      carcinoma are also discussed.

PMID- 19169962
TI  - Potency assays for novel T-cell-inducing vaccines against malaria.
AB  - The complex life cycle of the malaria parasite involves several developmental
      stages in the mammalian host that provide opportunities for vaccine intervention.
      The effector arm of the immune response that protects against malaria is specific
      for each stage of the parasite life cycle. While CD4+ and CD8+ T-cells are
      required to mediate protection during the liver stage, antibodies play a major
      role before parasite entry into the liver and during the blood stage. Induction
      of cytotoxic T-cells or those producing IFNgamma has become a major goal for T
      cell-inducing vaccines, and the liver stage is currently one of the preferred
      targets for malaria vaccine development. T-cells can effectively be primed by
      several vaccine strategies, including recombinant vectors. A wide range of such
      vectors is currently available and their use alone or in combination induces high
      frequencies of antigen-specific T-cells in animal models and humans. Therefore,
      traditional potency assays, such as the highly sensitive ex vivo and cultured
      ELISPOT, are being complemented by less sensitive, but more flexible techniques,
      such as flow cytometry, which allows characterization of multifunctional antigen
      specific T-cells following vaccination.

PMID- 19169963
TI  - Canakinumab, a fully-human mAb against IL-1beta for the potential treatment of
      inflammatory disorders.
AB  - Novartis AG is developing canakinumab, an intravenously or subcutaneously
      infused, fully human mAb that neutralizes the bioactivity of human IL-1beta,
      which is involved in several inflammatory disorders. Canakinumab has promising
      clinical safety and pharmacokinetic properties, and demonstrated potential for
      the treatment of cryopyrin-associated periodic syndromes (CAPS) and possibly for
      other complex inflammatory diseases, such as rheumatoid arthritis, systemic-onset
      juvenile idiopathic arthritis (SoJIA), COPD disease and ocular diseases.
      Currently in phase III clinical development, canakinumab was recently granted EU
      and US Orphan Drug status for SoJIA and CAPS. Early clinical trials have
      established the administration of canakinumab every 2 weeks to be safe and
      effective, offering a considerable advantage over the existing treatment with the
      human IL-1 receptor antagonist anakinra, which must be injected daily and which
      is often poorly tolerated by patients. The availability of more than one IL-1
      targeting biological agent is undoubtedly advantageous, not only for patients and
      clinicians, but also for the elucidation of disease mechanisms.

PMID- 19169964
TI  - IC-51, an injectable vaccine for the prevention of Japanese encephalitis virus
      infection.
AB  - The mosquito-borne Japanese encephalitis (JE) virus is the major etiological
      agent of viral encephalitis in children living in South-East Asia, causing comas,
      seizures and Parkinson's disease-like movement disorders. Travelers and military
      personnel visiting the region are also highly susceptible to the disease. As the
      population in South-East Asia increases, more land is irrigated to produce rice
      paddies (the ideal breeding habitat for mosquitoes), and pig breeding (a zoonotic
      host for mosquitoes) becomes more widespread. Given the exponential growth in
      tourism to the region and the globalization of business and commerce, an enhanced
      requirement for mass vaccination exists. In the West, the current licensed
      vaccine against JE, JE-VAX, has been highly effective; however, the use of mouse
      brain-derived virus has been linked to cases of acute disseminated
      encephalomyelitis. Intercell AG, under license from VaccGen International LLC, is
      developing IC-51, a formalin-inactivated vaccine derived from cell culture-based
      attenuated virus that has been adapted to grow in Vero cells (African green
      monkey kidney cells). In extensive clinical trials performed to date, IC-51 was
      safe, with mild to moderate adverse events reported. In terms of immunogenicity,
      IC-51 was highly effective, demonstrating rapid seroconversion rates and long
      term maintenance of geometric mean titers that exceeded the protective titer. The
      results suggests that IC-51 is fully compliant with the stringent regulatory
      requirements set by the WHO, has an acceptable safety profile and is non-inferior
      to JE-VAX.

PMID- 19169965
TI  - Spatial correlations between beta-amyloid (Abeta) deposits and blood vessels in
      familial Alzheimer's disease.
AB  - In sporadic Alzheimer's disease (SAD), the classic ('dense-cored') beta-amyloid
      (Abeta) deposits are aggregated around the larger blood vessels in the upper
      laminae of the cerebral cortex. To determine whether a similar relationship
      exists in familial AD (FAD), the spatial correlations between the diffuse,
      primitive, and classic beta-amyloid (Abeta deposits and blood vessels were
      studied in ten FAD cases including cases linked to amyloid precursor protein
      (APP) and presenilin (PSEN) gene mutations and expressing apolipoprotein E (apo
      E) allele E4. Sections of frontal cortex were immunolabelled with antibodies
      against Abeta and with collagen IV to reveal the Abeta deposits and blood vessel
      profiles. In the FAD cases as a whole, Abetadeposits were distributed in
      clusters. There was a positive spatial correlation between the clusters of the
      diffuse Abetadeposits and the larger (>10 microm) and smaller diameter (<10
      microm) blood vessels in one and three cases respectively. The primitive Abeta
      deposits were spatially correlated with larger and smaller blood vessels each in
      four cases and the classic deposits in three and four cases respectively. Apo E
      genotype of the patient did not influence spatial correlation with blood vessels.
      Hence, spatial correlations between the classic deposits and larger diameter
      blood vessels were significantly less frequent in FAD compared with SAD. It was
      concluded that both Abeta deposit morphology and AD subtype determine spatial
      correlations with blood vessels in AD.

PMID- 19169966
TI  - Association between genetic and environmental factors and the risk of Alzheimer's
      disease.
AB  - The only well confirmed genetic risk factor for sporadic Alzheimer's disease (AD)
      is the possession of apolipoprotein E (APOE) epsilon4 allele. As it contributes
      to 40-70% of AD cases, a large proportion of genetic variance may be determined
      by additional loci. Our aim was to estimate how reported genetic factors (APOE,
      NOS3, MTHFR) interact to increase the risk for AD and combine them with
      environmental factors (homocysteine, vitamin B12, cholesterol). Genotyping was
      performed in 154 AD patients and 176 healthy controls. Levels of homocysteine,
      vitamin B12 and cholesterol were assessed in subgroups of 100 AD patients and 100
      controls. We found a difference in APOE epsilon4 and NOS3 G/G distribution
      between groups (p<0.005). Plasma total homocysteine was increased and vitamin B12
      decreased in AD patients (p<0.001). The influence of APOE epsilon4 and NOS3 G
      alleles on the risk of AD was independent of homocysteine, vitamin B12 levels and
      MTHFR status.

PMID- 19169967
TI  - Amyloid angiopathy in idiopathic Parkinson's disease. Immunohistochemical and
      ultrastructural study.
AB  - The prevalence of cerebral amyloid angiopathy (CAA) and its association with
      intellectual decline in idiopathic Parkinson's disease (iPD) remain unclear. To
      identify the role of CAA in iPD dementia the prevalence and severity of CAA were
      investigated, with particular respect to changes in vessel wall structure. Twenty
      eight autopsy Parkinsonian brains and fourteen age-matched controls, post-mortem
      revised histopathologically for the presence of alpha-synuclein and Alzheimer's
      disease (AD)-type pathology, using standardized clinico-neuropathological
      criteria, underwent further investigation. Histological, immunohistochemical
      staining methods with antibodies to amyloid beta-peptide, alpha-actin, collagen
      III, collagen IV and CD34 as well as ultrastructural methods were used. The
      findings showed that the prevalence of CAA in the iPD cohort was higher (53%)
      than in controls (28%). CAA occurred more frequently in the iPD+AD (70%) sub-set
      than in the iPD-AD (44%) one. The progression of CAA was differentiated, with
      predominance of mild stage. Diminished smooth muscle actin and collagen IV
      expression in the vascular media with concomitant collagen III positive
      immunoreactivity in the intima were observed only in very severe CAA.
      Ultrastructural assay revealed degenerative changes in vessel smooth muscle cells
      and thickening of their basement membrane with the focal accumulation of amyloid
      fibres and fibrillar collagen in both iPD -AD and iPD+AD cases, but the most
      severe CAA-type changes were visible in the iPD+AD sub-set. The same type of
      immunoreactivity (Abeta42 positive and Abeta40 positive) of arterial CAA and
      parenchymal neuritic plaques, as well as capillary CAA and diffuse plaques
      (Abeta42 positive and Abeta40 negative), may indicate pathogenic similarities and
      differences between both types of degenerative changes on the one hand and time
      different changes or local different processing of amyloid precursor protein on
      the other.

PMID- 19169968
TI  - Morphological changes in the brain during experimental hyponatraemia. Do
      vasopressin and gender matter?
AB  - Hyponatraemia is the most common electrolyte balance disorder occurring in
      hospitalized patients. The disease results frequently from inappropriate
      secretion of vasopressin (SIADH). It has been evidenced that the brain
      consequences of hyponatraemia are more dramatic in young females than in men or
      postmenopausal women. Since both vasopressin and oestrogen have been reported to
      inhibit ion fluxes essential for the adaptation of the brain to the lowering of
      serum sodium concentration, we sought to study the effect of acute and chronic
      hyponatraemia or hyponatraemia associated with vasopressin on brain morphology in
      male and female rats. Hyponatraemia was induced with vasopressin (AVP) or with
      desmopressin (dDAVP) in 12 male and 12 female adult Wistar rats for either 3
      hours (acute) or 3.5 days (chronic). The brains of the animals with diagnosed
      hyponatraemia were fixed in 10% formalin and, following the standard procedure,
      stained with haematoxylin and eosin. Acute hyponatraemia resulted in white matter
      oedema with no obvious differences between genders or between groups with AVP- or
      dDAVP-induced hyponatraemia. Although in chronic hyponatraemia most neurons and
      astrocytic nuclei appeared to be normal, some neurons were swollen or ischaemic
      ("dark" neurons) and astrocytes showed a weak reaction. The most spectacular
      differences between males and females were found in the appearance of blood
      vessels. Swollen endothelial cells were observed more frequently in female than
      in male brains and in AVP- than in dDAVP-induced hyponatraemia. The widened
      Virchow-Robin spaces indicated perivascular oedema and blood-brain barrier
      damage. The results point to limited vascular adaptation to AVP-associated
      hyponatraemia in female gender.

PMID- 19169969
TI  - The cycloid and skeletonization methods for morphometric analysis of fetal brain
      vessels.
AB  - In our study, we examined 54 images from 9 fetal brains from the 11th to 22nd
      gestation week (GW). We measured the length density (LD) of vessels
      (microm/microm2) in the cortical grey matter (CGM) and in the cortical white
      matter (CWM). The aim of this work was to find a method which could be applied to
      measure the length density of vessels on two-dimensional (2D) sections. The first
      method (cycloid method) was based on cycloid function based on Stereo
      Investigator Software (MicroBrightField). The length in 2D could be estimated on
      the basis of a number of intersections between a line-probe and the linear
      objects of interest. In the study, we used a line-probe with systematically
      spaced sine-weighted curves (cycloids) of known length. In this case, the
      cycloids were 53.1 microm long. The counting grid was constructed from sine
      weighted lines (cycloids), which were used for estimation of the length density
      of vessels. The second method (skeletonization) was based on the mathematical
      functions of morphology and colour system transformation. The "binary airway
      tree" formed by the image segmentation step was skeletonized to identify two- or
      three-dimensional centrelines of individual branches, and to determine the branch
      point locations. The idea was to utilize a skeletonization algorithm which was
      based on properties of the average outward flux of the gradient vector field of a
      Euclidean distance function from the boundary of the structure. Both of these
      methods (cycloid and skeletonization) could be applied in measuring the length
      density of vessels on two-dimensional (2D) sections. These morphometric methods
      allowed us to measure the length density in fetal development of vessels in the
      cortical grey matter and the cortical white matter. The cycloid method could be
      applied to measure an approximate length density of vessels. However,
      skeletonization should be applied to measure more precisely length density of
      vessels in the cortical grey matter and the cortical white matter.

PMID- 19169970
TI  - Granular cell astrocytoma. A case report with immunohistochemical and
      ultrastructural characterization.
AB  - Granular cell astrocytoma (GCA) is an uncommon type of granular cell tumours
      (GCTs) in the central nervous system. Granular cells in these tumours are of
      enigmatic origin. We report a case of cerebral GCA in a 59-year-old man who
      suffered from diabetes and Addison-Biermer disease. The tumour was localized in
      the left parietal lobe. Microscopically, the tumour was almost entirely composed
      of large, polygonal cells with round to oval, granular eosinophilic, PAS-positive
      cytoplasm. The nuclei were located centrally or eccentrically and sometimes
      exhibited nucleolar vacuoles. The tumour cells were arranged in nests surrounded
      by blood vessels and connective tissue. Immunohistochemically, the granular
      tumour cells were reactive for GFAP and vimentin. They were intensively stained
      for ubiquitin and some of them were reactive for CD68. Moreover, a lot of stromal
      cells expressed CD68 reactivity. Ultrastructurally, most tumour cells were round
      or oval with only a few or without filaments. Their cytoplasm was filled with
      electron-dense granular material limited by a single membrane and autophagic
      vacuoles. Another type of tumour cells, present in a significantly lower number,
      revealed abundant cytoplasm with numerous intermediate filaments, swollen rough
      endoplasmic reticulum, mitochondria and a few clusters of granular material.
      Cells with numerous condensed electron-dense, bizarrely-shaped mitochondria and
      few filaments were occasionally observed. Among granular cells, macrophages with
      vacuoles and/or lamellar structures were visible. In our case, both
      immunohistochemical and ultrastructural analysis supported astroglial origin of
      the granular cell tumour.

PMID- 19169971
TI  - Prolonged QRS duration in patients with heart failure: relation to exercise
      tolerance, diastolic function and aetiology.
AB  - BACKGROUND: In patients with chronic heart failure (CHF) QRS prolongation is a
      frequent finding and is related to increased morbidity and mortality. It is not
      clear if prolonged QRS in CHF of ischaemic origin (CAD) represents the same
      severity of the syndrome as in non-ischaemic (non-CAD) cardiomyopathy. AIM: To
      assess the relationship between QRS duration and BNP levels, diastolic function
      and peak VO2 in patients with CAD CHF and non-CAD CHF. METHODS: In 70 patients
      with left ventricular ejection fraction (LVEF) <45% [35 with left bundle branch
      block (LBBB)] echocardiography, cardiopulmonary exercise test and standard ECG
      were performed as well as BNP level was measured. RESULTS: Peak VO2 was
      significantly lower, BNP level higher in patients with LBBB than those without
      LBBB. In the non-CAD CHF peak VO2 was significantly lower, whereas BNP levels and
      restrictive filling pattern prevalence higher in the group with LBBB than without
      LBBB, which was not seen in the CAD CHF group. A significant correlation between
      peak VO2 and BNP levels (r=-0.31; p=0.02), QRS duration (r=-0.27; p=0.02), and
      diastolic function parameter - DTE (r=0.28; p=0.02) was found. Peak VO2 was
      significantly lower in the CAD CHF than in non-CAD CHF. In multivariate
      regression analysis, LVEF (r=-0.32; p=0.012) and LVEDD (r=0.30; p=0.015) were
      independently associated with QRS duration. CONCLUSION: In patients with CHF, QRS
      duration is independently related to LVEF and LVEDD. It seems that prolonged QRS
      may be a better predictor of more advanced CHF in patients with non-ischaemic
      rather than ischaemic cardiomyopathy.

PMID- 19169972
TI  - Predictors of long-term outcome in patients with left ventricular dysfunction
      following coronary artery bypass grafting.
AB  - BACKGROUND: Prognostic significance of clinical and non-invasive risk markers in
      patients after surgical revascularisation remains unclear, especially in post
      infarction patients with left ventricular (LV) dysfunction. AIM: The single
      centre, prospective study was designed to assess survival and the predictive
      power of several clinical and non- -invasive risk markers of all-cause (ACM) and
      cardiovascular mortality (CVM) in post-CABG patients with LV dysfunction.
      METHODS: A cohort of 61 patients (age 59+/-9 years, 49 males, LVEF 33+/-6%) 6-12
      months after CABG was prospectively followed for a median of 46 months.
      Demographics, clinical data, medication, LVEF, QRS>120 ms or late potentials (LP)
      presence, QT dispersion l80 ms, premature ventricular contractions (PVC) l10/h,
      non-sustained ventricular tachycardia (nsVT), and SDNN L70 ms in ambulatory ECG
      were analysed. The ACM and CVM were evaluated. The prognostic value of analysing
      parameters was determined. RESULTS: Fourteen patients died, 10 of them due to
      cardiovascular causes. Univariate Cox analysis showed that incomplete
      revascularisation, history of angina, heart failure, low LVEF, use of nitrates,
      digitalis or diuretics, and presence of LP or prolongation of QRS complex were
      predictors of poor outcome. Combination of angina and low LVEF was the best model
      in a multivariable Cox analysies for the prediction of both types of death.
      CONCLUSIONS: The present study showed that in post-CABG patients with LV
      dysfunction, angina class and low LVEF are the main predictors of ACM and CVM.
      Combination of LVEF <30% with the presence of QRS >120 ms or LP may also be
      helpful in the identification of high-risk subjects. Other common non-invasive
      risk markers, particularly arrhythmic and autonomic, seem to lose some of their
      predictive power in patients after CABG and receiving beta-blocking agents.

PMID- 19169973
TI  - Carrier-state of two or three polymorphic variants of MTHFR, IL-6 and ICAM1 genes
      increases the risk of coronary artery disease.
AB  - BACKGROUND: Progression of coronary artery disease (CAD) depends on multiple
      genetic and environmental factors. Polymorphic variants of genes encoding
      proteins involved in endothelium dysfunction or proinflammatory state may
      genetically differentiate the human population and determine a susceptibility to
      the disease. AIM: To find the relationship between single polymorphisms of MTHFR,
      IL-6 and ICAM1 genes, double or triple combinations among their polymorphic
      variants and CAD in a patient population from the Upper Silesia region. METHODS:
      The study population consisted of 177 patients with angiographically documented
      CAD and 202 blood donors with no signs of CAD. All examined individuals were
      white Polish Caucasians aged 18-55 years. The analysis of genetic polymorphisms
      was performed using the PCR-RFLP method. RESULTS: We observed a weak association
      between single gene polymorphism and the disease only in the case of the MTHFR T
      allele. We also found that the frequency of some double or triple combinations
      among analysed genes, especially for MTHFR+ICAM1 and MTHFR+ICAM1+IL-6 patterns,
      differentiated the entire patient group from controls (p=0.047 OR=1.75 and
      p=0.016 OR=1.75, respectively). These two combinations were also significantly
      more frequent in patients who were age-matched with controls, especially in the
      female subgroups (for MTHFR+ICAM1 p=0.007, OR=10.32 and for MTHFR+ ICAM1+IL-6,
      p=0.005, OR=17.95 in females). CONCLUSION: The present study showed that
      simultaneous carrier-state of MTHFR, IL-6 and ICAM1 genes increased the risk of
      CAD.

PMID- 19169974
TI  - Serum levels of interleukin-6, interleukin-10 and C-reactive protein in relation
      to left ventricular function in patients with myocardial infarction treated with
      primary angioplasty.
AB  - BACKGROUND: Inflammatory factors are involved in the cardiac remodelling process
      after myocardial infarction (MI). Pronounced and sustained activation of
      proinflammatory factors is believed to enhance the damage to the myocardium and
      leads to its dysfunction and heart failure. Anti-inflammatory factors, especially
      interleukin-10 (IL-10), exert a protective action by reducing excessive
      inflammatory reactions. AIM: To asses the relationship between serum levels of IL
      6, IL-10, CRP and echocardiographic indices of myocardial function in patients
      with ST-elevated myocardial infarction (STEMI) treated with primary angioplasty.
      Prognostic value of IL-6, IL-10 and CRP levels in predicting systolic and
      diastolic dysfunction 6 months after MI was also assessed. METHODS: We studied 75
      patients aged 36-82 (28 women and 47 men) presenting with STEMI treated with
      primary angioplasty. Blood samples for assesment of IL-6, IL-10 and CRP levels
      were on days 3 and 7 (3d, 7d) of MI and after 6-month follow-up (6m).
      Echocardiographic examination was performed on day 7 and 6 months after MI during
      which the parameters of LV systolic (LVEF, WMSI) and diastolic function (E/A, DT,
      IVRT, Ep, E/Ep) were evaluated. Twenty four healthy persons served as controls.
      RESULTS: Interleukin-6 and CRP levels in consecutive measurements correlated
      significantly inversely with LVEF (7d) and LVEF (6m). The IL-10 (7d) and IL-10
      (6m) level correlated positively with LVEF (6m) (r=0.39, p=0.02; r=0.27, p=0.04).
      The IL-6 and CRP levels in consecutive measurements correlated significantly
      positively with E/A and E/Ep and inversely with IVRT, DT and Ep. The IL-10 (3d)
      level correlated inversely with DT (6m) (r=-0.25, p=0.04), while IL-10 (7d) level
      correlated positively with DT (6m) (r=0.36, p=0.004). Increased level of IL-6
      (3d) and CRP (3d) was an independent prognostic factor of LV systolic (OR=1.27,
      p=0.02; OR=1.14, p=0.05) and diastolic dysfunction (OR=1.14, p=0.03; OR=1.05,
      p=0.01) 6 months after MI. CONCLUSIONS: 1. A significant, correlations between
      increased IL-6, CRP level and impaired LV systolic and diastolic function
      indicate the possible involvement of these factors in postinfarction cardiac
      damage. 2. Increased level of IL-6 and CRP in the acute phase of MI is an
      independent predictor of LV systolic and diastolic dysfunction 6 months after MI.
      3. Increased serum level of IL-10 in the acute phase of MI reflects the extension
      of post-infarction myocardial lesion. 4. Maintenance of increased level of IL-10
      for days/months after MI seems to be prognostically beneficial.

PMID- 19169975
TI  - Clinical significance of heart rate turbulence assessment in patients with
      chronic heart failure.
AB  - BACKGROUND: Heart rate turbulence (HRT) is modulated by the baroreceptor reflex,
      and it has been suggested that it could be used as a measure of autonomic
      dysfunction. Impaired HRT has a significant prognostic value in patients after
      myocardial infarction. The usefulness of HRT parameters in CHF patients has not
      yet been well established. AIM: To assess the relationship between HRT
      parameters, clinical course of CHF and selected biochemical markers with respect
      to their prognostic value in CHF patients. METHODS: A 64 of 100 consecutive CHF
      patients, in whom it was possible to calculate HRT, were divided into four groups
      according to NYHA class. Uric acid (UA) and brain natriuretic peptide (BNP)
      concentrations were measured. Heart rate turbulence was analysed from 24-hour
      Holter ECG and characterised by two parameters: turbulence onset (TO) and
      turbulence slope (TS). The results of 20 healthy persons served as a control
      group. Follow-up examinations were performed after 6 and 12 months. RESULTS: In
      patients with CHF both HRT parameters (TO and TS) were significantly impaired in
      comparison to TO and TS in healthy subjects. A negative correlation between these
      parameters was found. A strong positive correlation between TO and NYHA class and
      a significant negative correlation between TS and BNP and UA concentrations were
      observed. There were 11 deaths during one-year follow-up. Patients who died due
      to CHF had significantly lower TS and higher TO values in comparison to
      survivors. CONCLUSIONS: Heart rate turbulence is impaired in CHF patients. HRT
      parameters show a significant correlation with some clinical factors: NYHA class,
      BNP and UA concentrations. Both HRT parameters, TO and TS, seem to be significant
      prognostic markers in patients with CHF.

PMID- 19169976
TI  - Persistent left and absent right superior vena cava.
AB  - Persistent left and absent right superior vena cava is a rare congenital anomaly,
      which is usually asymptomatic and discovered incidentally. A 57-year-old female
      patient was referred to this hospital for valvular surgery. Preoperative
      echocardiography and computed tomography revealed the diagnosis of persistent
      left and absent right superior vena cava. Mitral and aortic valve replacements
      were successfuly performed using aortic and single inferior vena cava
      cannulations with antegrade cardioplegic infusion. Cardiovascular surgeons or
      cardiologists should be aware of its presence in advance of a pertinent
      manoeuvre.

PMID- 19169977
TI  - [Acute myocardial infarction due to thrombosis of coronary artery aneurysm in a
      29-year-old women during postpartum period].
AB  - Acute myocardial infarction during pregnancy and postpartum period is rare. A
      case of a 29-year-old female who developed acute myocardial infarction during
      postpartum period is presented. Coronary angiography revealed thrombosis of a
      coronary artery aneurysm of the marginal branch. The patients was treated
      conservatively and during 5 months of follow-up the clinical course was
      uneventful.

PMID- 19169978
TI  - [Heparin-induced thrombocythopenia in a patient with massive pulmonary embolism
      and dilated cardiomyopathy, successfuly treated with fondaparinux - a case
      report].
AB  - Heparin-induced thrombocythopenia (HIT) is a potentially serious complication of
      heparin treatment, rarely observed in cardiological wards. We present a case of a
      38-year-old woman with dilated cardiomyopathy and massive pulmonary embolism
      treated with alteplase and unfractionated heparin. On 12th day an unexpected fall
      in platelet count was observed, without new signs of thrombosis. The HIT type II
      was diagnosed. Patient was treated effectively and safely by 7.5 mg of
      fondaparinux given subcutaneously once daily for 10 days.

PMID- 19169979
TI  - [Acute aortic dissection type A with concomitant myocardial infarction].
AB  - The authors describe a patient with acute aortic dissection type A complicated by
      left main coronary artery occlusion and acute myocardial infarction. The patient
      underwent urgent surgery, however, died 4 hours after operation.

PMID- 19169980
TI  - [Do angiotensin receptor blockers increased the risk of myocardial infarction?
      The landscape after ONTARGET study].

PMID- 19169981
TI  - [Depression in patients with chronic heart failure].

PMID- 19169982
TI  - [QTc duration in the long QT syndrome type 2 - diagnostic dilemma].
AB  - We present a case of a 43-year old woman with a long QT syndrome (LQTS). Despite
      her family history of several sudden deaths in close relatives the patient was
      misdiagnosed, being treated many years for epilepsy. Finally, after another
      series of syncopal spells she was diagnosed with LQTS. Although QTc interval was
      normal on surface ECG, the presence of notched T-waves and QT prolongation up to
      543 ms on Holter recording were helpful in establishing the correct diagnosis,
      which was later confirmed by genotyping revealing G601S mutation in the HERG
      gene. The patient refused an ICD and despite beta-blocker treatment died suddenly
      several months later.

PMID- 19169983
TI  - [Giant left ventricular postinfarction pseudoaneurysm - an echocardiographic case
      report].
AB  - We present a rare case of a 71-year-old man who had myocardial infarction 9 years
      ago. Transthoracic and transesophageal echocardiography revealed presence of a
      large pseudoaneurysm of the left ventricular (LV) apex and anterior wall with
      thrombus. The diagnosis of LV pseudoaneurysm was confirmed by electrocardiography
      - gated multidetector computed tomography. The patient did not consent for
      surgery and remained on pharmacological treatment.

PMID- 19169984
TI  - [Percutaneous closure of a congenital coronary artery fistula with the use of
      graftstent - a case report].
AB  - The congenital coronary fistula is a rare anomaly revealed sometimes during
      diagnostic procedures. Although it is rarely symptomatic many authors consider
      elective procedure of closure, because of relatively low risk of procedure. This
      case demonstrate the percutaneous closure of a congenital coronary artery fistula
      using graftstent.

PMID- 19169985
TI  - [Glass of water or ablation? - episodes of malignant atrial tachyarrhythmias
      during swimming in a lake in a woman with overt Wolff-Parkinson-White syndrome
      and benign palpitations for several decades of life].
AB  - We present a case of a 41 year old woman with overt Wolff-Parkinson-White
      syndrome (WPW) and benign palpitations for over four decades of life who suffered
      from a malignant atrial tachyarrhythmias (typical atrial flutter concomitant with
      left atrial fibrillation) during swimming in a lake. Loading dose of amiodarone
      increased frequency of attacks of sustained AVRT. In spite of treatment with
      amiodarone, effective refractory period of accessory pathway was still short.
      After ablation of accessory pathway, during five years of follow-up, there was no
      arrhytmia recureence.

PMID- 19169986
TI  - [Transapical aortic valve implantation - hope for high risk patients with severe,
      symptomatic aortic stenosis - a case report from the first procedures performed
      in Poland].

PMID- 19169987
TI  - [Training requirements for transvenous implantation of pacemakers and
      cardioverter-defibrillators].
AB  - Therapy with implantable pacemakers, cardioverter defibrillators (ICD), and
      devices for cardiac resynchronization (CRT) is performed by various medical and
      surgical specialists. With the change from implantation by thoracotomy to the
      transvenous approach, an increasing number of devices are implanted by
      cardiologists. The purpose of this paper is to establish training requirements
      for transvenous device therapy, implantation and follow-up examinations,
      regardless of the implanting person, an internist, cardiologist, general surgeon,
      or cardiothoracic surgeon. Epicardial lead placement should be performed only by
      surgeons. Two levels of training topics are defined, level 1 for pacemakers and
      level 2 for ICD and CRT devices. Surgery that involves the implantation of
      foreign material should demand the highest standards of operating rooms design
      and environment. Catheter laboratories used for implantations should meet
      operating room standards. Complications need to be documented carefully for
      quality control.

PMID- 19169988
TI  - Neutrophil apoptosis by Fas/FasL: harmful or advantageous in cardiac surgery?
AB  - Polymorphonuclear leukocytes or neutrophils are the main executors of cellular
      death, both in septic inflammation during bacterial infection and in sterile
      inflammation during trauma or surgery. Whereas in septic inflammation neutrophils
      perform a useful function to fortify the host's defense against infection, in
      sterile inflammation, by contrast, they contribute to unwelcome tissue damage.
      Regardless of the situation, activated neutrophils exhibit a prolonged lifespan
      and delayed apoptotic death which, under normal conditions, is a prerequisite for
      their natural renewal. Traditionally, delayed neutrophil apoptosis was considered
      to promote trauma or surgical injury. According to the results of recent studies,
      however surprising they may appear, the reverse might be in keeping with what
      happens IN VIVO. Apoptotic signaling in neutrophils could, by contrast,
      contribute to intrinsic protection of the host's tissues. This review article,
      aimed preferentially but not exclusively at the cardiac surgeon, presents some
      new information in support of this viewpoint, which fits in with our own
      observations.

PMID- 19169989
TI  - Histological changes in neonatal kidneys after cardiopulmonary bypass and deep
      hypothermic circulatory arrest.
AB  - BACKGROUND: Renal failure after open-heart surgery is a serious complication
      resulting in increased mortality and morbidity. The aim of the study was to find
      out whether different strategies for open-heart surgery would result in renal
      histological differences in a neonatal animal model. METHODS: The renal tissue of
      newborn piglets was examined after mild hypothermic cardiopulmonary bypass (CPB
      group; n = 10), deep hypothermic circulatory arrest (DHCA group; n = 8),
      instrumentation without extracorporeal circulation (sham; n = 3), and the data
      were compared with those of normal porcine neonatal kidneys (control; n = 6). The
      severity of tissue damage was graded using a 4-point scoring system (0: normal
      morphology, 3: severe damage). Apoptotic cells and granulocytes were counted.
      RESULTS: The histological score was higher in all groups compared with controls (
      P < 0.05) and higher in the CPB group compared with the DHCA group ( P < 0.05).
      More apoptotic cells and granulocytes were found in the CPB group compared with
      controls and the DHCA group ( P < 0.05). CONCLUSIONS: Although changes in the
      kidney tissue of newborn piglets are detectable after any cardiac procedure,
      changes are more profound after cardiopulmonary bypass with mild hypothermia.

PMID- 19169990
TI  - A novel pulse duplicator system: evaluation of different valve prostheses.
AB  - BACKGROUND: The hemodynamic characteristics of different heart valve prostheses
      have been investigated in vitro with a novel pulse duplicator. A novel valved
      stent for transapical or percutaneous valve implantation has been compared with a
      native heart valve and mechanical heart valves. METHODS: All experiments were
      designed to imitate both physiologic pressure ratios and flow characteristics in
      diastole and systole. After calibrating the system using a human aortic valve
      (primary orifice diameter: 22.0 mm), the following valves were studied under
      aortic pulsatile flow conditions: Hall-Kaster (Medtronic-Hall, 20.0 mm), St. Jude
      Medical (20.0 mm), a newly developed tricuspid valved stent (Tricumed TM4, 20.7
      mm) and a newly developed biomechanical valve (Engage aortic valve Model 6000,
      21.0 mm). All valves including the human aortic valve were assessed by videotape
      observation under pulsatile flow conditions. Measured flow-related parameters
      include in vitro mean transvalvular pressure, regurgitant volume, effective
      orifice area and performance index. RESULTS: The optical assessment of all five
      valves demonstrated a complete opening during systole and closing at the
      beginning of diastole. All valves were optically sufficient during diastole.
      Engage aortic valve Model 6000 showed the highest maximum transvalvular pressure
      (27.5 +/- 8.2 mmHg), whereas both Hall-Kaster (17.9 +/- 1.5 mmHg) and St. Jude
      Medical (16.7 +/- 0.7 mmHg) had a lower gradient than the native aortic valve
      (24.0 +/- 0.2 mmHg) and Tricumed TM4 (21.8 +/- 3.8 mmHg). The maximum effective
      orifice area of St. Jude Medical amounted to 258.7 +/- 3.4 mm(2), followed by
      Tricumed TM4 with an area of 222.1 +/- 1.9 mm(2) and the human aortic valve with
      160.4 +/- 2.9 mm(2). Hall-Kaster and Engage aortic valve Model 6000 had an area
      of 198.9 +/- 1.6 mm(2) and 176.7 +/- 3.1 mm(2), respectively. CONCLUSIONS: The
      pulse duplicator proved to be highly accurate and yielded reproducible results.
      Since it has been calibrated with a human aortic valve, the hemodynamics of any
      heart valve prosthesis can be compared with the human valve. This system can
      evaluate and promote the development of new biological and mechanical heart valve
      prostheses.

PMID- 19169991
TI  - Preoperative platelet inhibition with ASA does not influence postoperative blood
      loss following coronary artery bypass grafting.
AB  - INTRODUCTION: Platelet inhibition is thought to increase perioperative blood loss
      in patients with planned coronary artery bypass grafting (CABG). This
      retrospective study reviews the results of over 10 000 patients with CABG,
      comparing continued platelet inhibition with preoperative disruption of this
      therapy. PATIENTS AND METHODS: From 1995 to 2007, 12 023 patients underwent
      isolated CABG and were included in this study. The data were evaluated with
      regard to preoperative aspirin therapy, EuroScore relevant risk factors, and the
      operative results. Parameters of the operative outcome were in-hospital
      mortality, perioperative infarctions, reexploration rate, strokes, pericardial
      tamponade, blood transfusions, and perioperative drainage loss. RESULTS: The
      patients were divided into two groups: group A (continuous aspirin therapy till
      surgery [n = 2519]), and group B (patients with preoperative interruption of
      their aspirin therapy for at least five days [n = 9504]). There was no difference
      between the groups with regard to age, EuroScore (4.3 +/- 2.8 vs. 4.2 +/- 2.9),
      emergency cases (8.8 % vs. 8.7 %), left main stenoses (17.9 % vs. 17.6 %),
      duration of surgery (198 +/- 53 vs. 198 +/- 52 min.) and sex distribution. The
      postoperative drainage loss did not differ between groups A and B (834 +/- 781 ml
      vs. 902 +/- 811 ml), nor did the number of postoperatively administered red cell
      packages (0.88 +/- 2.7 vs. 1.01 +/- 2.9). When analyzing the three subgroups "on
      pump primary CABG", "OPCAB procedures", and "redo CABG", again no difference was
      found in the main outcome parameters. Only the redo CABG of group B had a higher
      reexploration rate compared to group A (5 % vs. 3.3 %, P < 0.05). CONCLUSION:
      Preoperative aspirin therapy does not seem to influence the operative outcome of
      isolated CABG. Therefore, the often given recommendation to stop this therapy
      prior to elective CABG procedures should be abandoned.

PMID- 19169992
TI  - Patients' needs during hospitalization in a cardiac surgery unit before and after
      coronary artery bypass graft surgery.
AB  - BACKGROUND: The aim of this study was to explore patients' needs and changes to
      these needs during a hospital stay for coronary artery bypass graft (CABG)
      surgery. METHODS: 70 patients (60 males; mean age = 64.1; SD = 8.9) reported
      their needs two days before and ten days after CABG surgery using a specifically
      developed 15-item questionnaire. Student's T-test was used to detect significant
      differences. RESULTS: Before CABG, patients rated the need for "preparation for
      surgery", and after CABG the need for "information about the correct handling of
      drugs", as the most important. The rating of "information about the correct
      handling of drugs" showed a significant increase after CABG surgery ( T(69) = -
      3.46; P < 0.001) and the need for a "letter with the latest scientific
      information on heart disease" was significantly reduced during this period (
      T(69) = 2.07; P = 0.04). CONCLUSIONS: The results indicate that preparation for
      surgery should be conducted very carefully without time pressure. Patients should
      receive more detailed information on prescribed drugs.

PMID- 19169993
TI  - Secretion of soluble ST2 - possible explanation for systemic immunosuppression
      after heart surgery.
AB  - BACKGROUND: Cardiopulmonary bypass is known to affect cytokine release leading to
      a generalized endogenous immune reaction similar to that described in sepsis,
      without having been explored in great detail. Therefore we evaluated the anti-
      and pro-inflammatory cytokine responses after heart surgery. METHODS: 16 patients
      who underwent coronary artery bypass graft (CABG) surgery with extracorporeal
      circulation were included. ST2, IL-4 and IL-10 served as markers for TH2 cytokine
      response; IL-6, IL-8 and IFN-gamma as TH1 markers. Furthermore, total
      immunoglobulin subtype analysis (IgM, IgG, IgE) was performed. RESULTS: Serum
      levels of soluble ST2 started to climb at 60 minutes (from 38 +/- 14
      preoperatively to 1 480 +/- 890 pg/ml) and peaked 24 hours after surgery (13 360
      +/- 2 840 pg/ml, P < 0.001). IL-10 reached a maximum at 60 minutes and returned
      to baseline levels 24 hours later. IL-6 and IL-8 levels peaked 60 minutes after
      surgery. IL-4 and IFN-gamma did not change. Only IgM showed a significant peak on
      day eight ( P < 0.001). CONCLUSION: Our results demonstrate that CABG surgery
      induces a massive long-lasting secretion of ST2, a protein related to immune
      suppression.

PMID- 19169994
TI  - Surgical treatment of multiple primary adenocarcinomas of the lung.
AB  - INTRODUCTION: The incidence of lung adenocarcinomas has steadily increased over
      the last decades. The aim of this study was to assess the results of surgical
      treatment of multiple primary adenocarcinomas of the lung (MPAL) analyzing the
      radiological and histological features. METHODS: From 1988 to 2005, 26 patients
      underwent surgical treatment for MPAL at our department, for a total of 52
      tumors. Three patients had synchronous and 23 had metachronous tumors. RESULTS:
      Thirty-seven tumors were classified as solid, two as ground-glass opacities (GGO)
      and 13 as mixed solid/GGO tumors on the basis of CT scan evaluation. Histology
      revealed 26 adenocarcinomas, five adenocarcinomas with a bronchioloalveolar (BAC)
      pattern and 21 BAC. There was no postoperative mortality. Five-year survival of
      patients with synchronous tumors was 66 %. Survival of patients with metachronous
      tumors was 95 % and 70 % from the first and second operation. Patients with stage
      II and III a tumors had significantly reduced survival rates ( P < 0.05).
      Survival was 60 % after lobectomy and 78 % after wedge resection. CONCLUSIONS:
      Surgical treatment of MPAL is associated with favorable results. Sublobar
      resections, when technically feasible, provide adequate oncological management.

PMID- 19169995
TI  - Prospective study on perioperative risks and functional results in bronchial and
      bronchovascular sleeve resections.
AB  - BACKGROUND: Most reports on sleeve resections are based on a retrospective
      analysis over a long period of many decades. This prospective study addresses the
      challenging questions associated with sleeve resection. METHODS: In a prospective
      study, 100 consecutive patients undergoing bronchial or bronchovascular sleeve
      resection with systematic lymph node dissection were analyzed: operative
      procedures, extended lymph node dissection, bronchial and vascular complications,
      functional results, recurrence and survival were recorded. RESULTS: 100 patients
      (male 78, female 22, age 60.0 +/- 11.9) were enrolled in this study. A R0
      resection rate of 99 % could be achieved and pneumonectomies avoided using 9
      different surgical techniques. The average number of dissected lymph nodes was 30
      on the right side and 33 on the left side. Morbidity and mortality were 39 % and
      2 %, respectively. The main indication was non-small cell lung cancer (74 %). The
      local and distant recurrence rates were 1 % and 16 %, respectively. The overall 5
      year survival rate was 87 %. Long-term survival differed significantly between N0
      and N1 status ( P = 0.027) and N0 and N2 status ( P = 0.029), but not between N1
      and N2 status ( P = 0.754). There were no relevant differences in pre- and
      postoperative perfusion scans and FEV (1) at 6 months after surgery. CONCLUSIONS:
      In the hands of experienced surgeons bronchial and bronchovascular sleeve
      resections are safe operations for high-risk patients. There is no statistical
      significance between N1 and N2 disease with regard to long-term survival.
      Systematic lymph node dissection does not lead to increased perioperative risk.
      Sleeve resections have little effect on pulmonary function. Preoperative FEV (1)
      and lung perfusion can be achieved by 6 months after surgery.

PMID- 19169996
TI  - Recurrent pleural effusion: who benefits from a tunneled pleural catheter?
AB  - Recurrent malignant pleural effusion (MPE) is a common concomitant phenomenon of
      malignant disease, which can worsen the patient's quality of life and lead to
      significant morbidity. Tunneled indwelling pleural catheters (TIPC) offer new
      modalities in patients with recurrent MPE and impaired dilatability of the lung.
      We report on our experience with 100 consecutive patients suffering from
      recurrent benign (n = 12) and malignant pleural effusion (n = 88) who were
      treated with TIPC. The catheter was placed during a VATS procedure or under local
      anesthesia in an open technique. The median residence time of the TIPC was 70
      days; spontaneous pleurodesis was achieved in 29 patients. The rate of
      complications was low: pleura empyema (n = 4), accidental dislodgement (n = 2),
      malfunction of the drainage (n = 3). In conclusion, TIPC is a useful method for
      the palliative treatment of patients with recurrent malignant or nonmalignant
      pleural effusions and 3 groups of patients seem to benefit most: a) patients with
      the intraoperative finding of a trapped lung in diagnostic VATS procedure; b)
      patients after a history of repeated pleuracenteses or previously failed attempts
      at pleurodesis; c) patients in a reduced condition with a limited lifespan due to
      underlying disease.

PMID- 19169997
TI  - Multiple cerebral aneurysms associated with cardiac myxoma in a patient with
      chronic renal failure: how can we resolve multiple cerebral aneurysms?
AB  - Left cardiac myxoma and consecutive embolization into the brain is well
      documented, whereas the association of myxoma with multiple fusiform cerebral
      aneurysms is rare. A 48-year old female with chronic renal failure had complained
      of syncope after receiving hemodialysis. An echocardiogram showed a 3 x 4 cm
      sized myxoma and brain MRI displayed multiple fusiform aneurysms. The myxoma was
      successfully removed. Postoperatively, she developed status epilepticus.
      Unfortunately, the patient did not recover and expired due to sepsis.

PMID- 19169998
TI  - Right ventricular outflow tract obstruction after bilateral lung transplantation.
AB  - We report here on the successful treatment for right ventricular outflow tract
      obstruction after bilateral lung transplantation in a patient with primary
      pulmonary hypertension. A 31-year-old female patient with primary pulmonary
      hypertension underwent successful bilateral lung transplantation. She had a
      pressure gradient of 30 mmHg through the right ventricular outflow tract one week
      after transplantation, but was successfully treated with atelenol and
      disopyramide. Long-term follow-up cardiac catheterization did not show any
      significant right ventricular outflow tract obstruction. The actual cause of the
      right ventricular outflow tract obstruction remained unknown, but longstanding
      pulmonary hypertension might have induced significant structural changes in the
      heart, such as right ventricular hypertrophy and enlargement.

PMID- 19169999
TI  - Surgical considerations on the use of the percutaneous ventricular assist device
      TandemHeart in critical aortic valve stenosis.
AB  - Decompensated aortic valve stenosis is a life-threatening condition. Aortic valve
      replacement in patients with cardiogenic shock due to critical aortic stenosis is
      a high-risk procedure and is associated with increased operative mortality. We
      describe the clinical course of a patient who was transferred to our institution
      in cardiogenic shock and with multiple organ failure, due to decompensated aortic
      valve stenosis. The patient received the percutaneous left ventricular assist
      device TandemHeart which has been developed for short-term cardiac support. After
      hemodynamic improvement the patient underwent successful aortic valve
      replacement. The device was left in place until the patient had recovered from
      surgery. The excellent outcome suggests that a perioperative mechanical support
      might greatly improve the safety of aortic valve replacement in the presence of
      cardiogenic shock.

PMID- 19170000
TI  - Switch from assist device to total artificial heart to improve cardiac output.
AB  - Left ventricular assist devices (LVADs) offer the opportunity to substantially
      improve the clinical condition and to interrupt the hospitalization of patients
      suffering from end-stage heart failure awaiting heart transplantation.We report a
      case of a 30-year-old patient (body surface area 2.49 m2) suffering from
      idiopathic dilative cardiomyopathy who was primarily given an LVAD with a free
      floating impeller pump and was finally switched to a total artificial heart due
      to the demand for a higher cardiac output.

PMID- 19170001
TI  - Acquired left ventricular-right atrial communication and severe aortic valve
      regurgitation caused by infective endocarditis.
AB  - We report here on a surgical case of acquired left ventricular right atrial
      communication (LV-RA communication) and aortic regurgitation (AR) caused by
      infective endocarditis (IE). We successfully treated the patient with composite
      patches made from polytetrafluoroethylene (PTFE) and autologous pericardium. In
      general, LV-RA communication is a rare congenital cardiac anomaly (Gerbode-type
      shunt). However, acquired LV-RA communications secondary to IE are occasionally
      reported.When repairing an acquired condition due to IE, particular care should
      be taken to avoid recurrence, persistent infection and iatrogenic
      atrioventricular block.

PMID- 19170002
TI  - Necrotizing mediastinitis linked to Boerhaave's syndrome: a surgical approach.
AB  - We report 5 cases of Boerhaave's syndrome with necrotizing mediastinitis and
      pleural empyema. We chose a surgical treatment characterized by manual suture and
      heterologous tissue to repair esophagus rupture. This option allows a better
      result in terms of morbidity and mortality.

PMID- 19170003
TI  - Multiple synchronous bronchial carcinoid tumors: report of a case.
AB  - Peripheral bronchial carcinoids are uncommon. Their presentation as synchronous
      tumors is rare and limited to anecdotal cases.We report the case of a 62-year-old
      female with the radiological finding of multiple bilateral nodular lesions.
      Bilateral sequential thoracotomies were performed and all three nodules were
      treated by sublobar resections. Pathological examination revealed all specimens
      to be carcinoid tumors and subsequent investigation confirmed the lung as the
      primary site. A review of previous cases of multiple carcinoids is presented and
      the particularities of their management are discussed.

PMID- 19170004
TI  - Minimally invasive repair of post-pneumonectomy syndrome.
AB  - We report on a 42-year-old female who underwent right pneumonectomy for
      hemoptysis from an aspergilloma cavity. Several years postoperatively she
      complained of increasing shortness of breath, wheezing, and dyspnea upon
      exertion. Chest computed tomography showed a counterclockwise rotation of the
      mediastinum with obstruction of the left lower lobe bronchus. Minimally invasive
      repair was carried out using an intrapleural tissue expander for dissection and
      an adjustable saline prosthesis for mediastinal centralization. Intraoperative
      bronchoscopy showed complete resolution of the left lower lobe bronchial
      obstruction, and postoperatively her symptoms resolved completely. This is the
      first reported case of a minimally invasive approach for the treatment of post
      pneumonectomy syndrome in the United States.

PMID- 19170020
TI  - Recommended tests for association in 2 x 2 tables.
AB  - The asymptotic Pearson's chi-squared test and Fisher's exact test have long been
      the most used for testing association in 2x2 tables. Unconditional tests preserve
      the significance level and generally are more powerful than Fisher's exact test
      for moderate to small samples, but previously were disadvantaged by being
      computationally demanding. This disadvantage is now moot, as software to
      facilitate unconditional tests has been available for years. Moreover, Fisher's
      exact test with mid-p adjustment gives about the same results as an unconditional
      test. Consequently, several better tests are available, and the choice of a test
      should depend only on its merits for the application involved. Unconditional
      tests and the mid-p approach ought to be used more than they now are. The
      traditional Fisher's exact test should practically never be used.

PMID- 19170021
TI  - Human iPS cell derivation/reprogramming.
AB  - This unit describes a protocol for deriving induced pluripotent stem (iPS) cells
      from human fibroblast cells. Human fibroblast cells are infected with retroviral
      vectors expressing four transcription factors (Oct4, Sox2, Klf4, and Myc) and
      selected for 3 to 4 weeks under human embryonic stem (hES) cell culture
      conditions. iPS cell colonies are mechanically isolated using a dissection
      microscope and handled like hES cells thereafter. Human iPS cells share
      similarities with hES cells including the expression of pluripotency genes, and
      differentiation as embryoid bodies in vitro into three germ layers (EB) and in
      vivo as teratomas.

PMID- 19170022
TI  - Evolution of neurotoxins: from research modalities to clinical realities.
AB  - In the 1950s, the discovery of anti-nerve growth factor, an immunotoxin stunting
      sympathetic neural development, signaled the advent of neurotoxins as research
      modalities. Other selective neurotoxins were discovered in rapid succession. In
      the 1960s, 6-hydroxydopamine and 6-hydroxydopa were shown to destroy
      noradrenergic and dopaminergic nerves. Excitotoxins (glutamate, aspartate, and
      analogs) were discovered in the 1970s. DSP-4 [N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine] proved to be selective for noradrenergic destruction, while 5,6
      and 5,7-dihydroxytryptamines were relatively selective for serotonin neurons.
      Additional neurotoxins were discovered, but it was MPTP (1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine) that predominated neurotoxicity research in the
      1980s. Eventually, Clostridium botulinum neurotoxin (BoNT), discovered as a
      "poisonous" principle in the late 1800s, resurfaced in purified and standardized
      forms as a clinically useful drug. Neurotoxins represent chemical tools, useful
      not only for discerning neuronal mechanisms and animal modeling of neurological
      disorders, but also for their use in medicine and potential as treatments for
      medical disorders. This unit reviews the early discovery of neurotoxins,
      describes categories of neurotoxins, and finally characterizes their usefulness-
      first as research tools, and eventually as clinical therapeutic agents.

PMID- 19170023
TI  - Identifying novel protein-protein interactions using co-immunoprecipitation and
      mass spectroscopy.
AB  - Proteomics has evolved from genomic science due to the convergence of advances in
      protein chemistry, separations, mass spectroscopy, and peptide and protein
      databases. Where identifying protein-protein interactions was once limited to
      yeast two-hybrid analyses or empirical data, protein-protein interactions can now
      be examined in both cells and native tissues by precipitation of the protein
      complex of interest. Coupling this field to receptor pharmacology has recently
      allowed for the identification of proteins that differentially and selectively
      interact with receptors and are integral to their biological effects. It is
      becoming increasingly apparent that receptors in neurons do not exist as singular
      independent units, but rather are part of large macromolecular complexes of
      interacting proteins. It is a primary quest of neuroscience to piece together
      these interactions and to characterize the regulatory signalplexes of all
      proteins. This unit presents co-immunoprecipitation-coupled mass spectroscopy as
      one way of identifying signalplex partners.

PMID- 19170024
TI  - An animal model of premenstrual dysphoric disorder sensitive to antidepressants.
AB  - Premenstrual dysphoric disorder (PMDD) is characterized by the recurrence of a
      cluster of physical and negative mood symptoms, especially irritability,
      appearing when estrogen and progesterone levels decrease during the late luteal
      phase of the menstrual cycle. This unit describes a new animal model of PMDD that
      shows differentiation between female rats expressing and not expressing ovarian
      cycle-dependent irritability measured by the behavior of burying harmless
      objects. Burying behavior is enhanced in a subgroup of female rats at metestrus
      and decreased at the proestrus phase of the estrous cycle. Increased marble
      burying at metestrus does not habituate and can be reversed by acute treatment
      with several antidepressants, which mimic the pharmacology of PMDD in humans.
      This model may be used to study the neuroendocrine mechanisms triggering
      premenstrual irritability, and the mode of action of antidepressants used for the
      treatment of PMDD.

PMID- 19170025
TI  - Selected suppliers of reagents and equipment.
AB  - This appendix lists the full contact information, including website URLs, for all
      suppliers mentioned in Current Protocols in Molecular Biology.

PMID- 19170026
TI  - Staining proteins in gels.
AB  - This unit describes protocols for detecting protein in a gel by Coomassie blue,
      silver, or fluorescent staining. As a general protein stain, Coomassie is easier
      and more rapid; however, fluorescent and silver staining methods are considerably
      more sensitive and thus can be used to detect smaller amounts of protein.
      Fluorescent staining is a popular alternative to traditional staining procedures,
      mainly because it is more sensitive than Coomassie staining, and often as
      sensitive as silver staining. Alternate protocols describe rapid Coomassie and
      silver staining methods, as well as fluorescent stains that are specific for
      phosphoproteins and glycoproteins. Staining of proteins in SDS-polyacrylamide
      gels is described; variations for fluorescent staining of proteins in
      nondenaturing gels are also included. Support protocols describe photography of
      stained proteins.

PMID- 19170027
TI  - Overview of mRNA expression profiling using DNA microarrays.
AB  - DNA microarray technology allows simultaneous measurement of the mRNA levels of
      thousands of genes. This powerful technology has applications in addressing many
      biological questions that were not approachable previously; however, the enormous
      size of microarray data sets leads to issues of experimental design and
      statistical analysis that are unfamiliar to many molecular biologists. The type
      of array used, the design of the biological experiment, the number of
      experimental replicates, and the statistical method for data analysis should all
      be chosen based on the scientific goals of the investigator. This overview
      presents a discussion of the relative merits and limitations of various methods
      with respect to some common applications of microarray experiments.

PMID- 19170028
TI  - Pattern discovery in expression profiling data.
AB  - In expression profiling studies, it is often necessary to identify groups of
      genes with similar expression profiles in a variety of samples, and/or groups of
      samples with similar expression profiles. Each profile can be expressed as a
      single data point in a space with the same number of dimensions as there are
      parameters in the profiles. In this way, pattern discovery among expression
      profiles is translated into pattern discovery in the spatial distribution of data
      points: the similarity between profiles is defined by the distance between the
      corresponding data points. Various multivariate analysis methods, such as
      clustering and dimensionality reduction methods, are used to summarize the data
      point distribution to help the investigator recognize major trends. As different
      methods may identify different features of the distribution, it is important to
      analyze a particular data set with multiple methods.

PMID- 19170029
TI  - Recombineering-based procedure for creating Cre/loxP conditional knockouts in the
      mouse.
AB  - Gene targeting in the mouse is an essential tool for studying gene function and
      creating models of human disease. The method described in this unit takes
      advantage of bacterial artificial chromosomes, Cre/loxP and FLPe/FRT systems, and
      recently evolved recombineering approaches to simplify the preparation of
      targeting constructs for generation of conditional knockout (CKO) animals. This
      method has been used to generate >30 CKO constructs, most of them successfully
      used to target mouse ES cells and establish mutant mice. Design and preparation
      of the CKO construct, as well as step-wise troubleshooting guidelines, are
      described in detail.

PMID- 19170030
TI  - Use of mouse models for the analysis of human disease.
AB  - The first half of this unit discusses the two main approaches to developing
      genetically engineered mouse models of human disease (i.e., transgenesis and gene
      targeting). The experimental steps for each method are discussed. Potential
      pitfalls, advantages, and limitations are also addressed. The second half of the
      unit describes two mouse models of hypertrophic cardiomyopathy, which illustrate
      the value of studying such models of human disease, both in terms of
      understanding disease pathogenesis as well as potential new therapeutic avenues.

PMID- 19170031
TI  - SNP genotyping using the Sequenom MassARRAY iPLEX platform.
AB  - The method for SNP genotyping described in this unit is based on the commercially
      available Sequenom MassARRAY platform. The assay consists of an initial locus
      specific PCR reaction, followed by single base extension using mass-modified
      dideoxynucleotide terminators of an oligonucleotide primer which anneals
      immediately upstream of the polymorphic site of interest. Using MALDI-TOF mass
      spectrometry, the distinct mass of the extended primer identifies the SNP allele.

PMID- 19170032
TI  - Preparation and culture of products of conception and other solid tissues for
      chromosome analysis.
AB  - In clinical settings, chromosome studies are usually performed on solid tissue
      other than solid tumors for one of two reasons: the tissue biopsy is the only
      tissue available from the patient, or tissues other than the standard peripheral
      blood lymphocytes must be examined because of suspected mosaicism. This unit
      describes methods for culturing tissue samples to be used for preparation of
      metaphase chromosomes or for biochemical or DNA analysis. Protocols include an
      efficient enzymatic cell disruption procedure and a mechanical disruption
      procedure. In addition, a procedure for processing uncultured cells for analysis
      by fluorescence in situ hybridization (FISH) is provided. Finally, a method is
      presented that can sometimes be applied to placental tissue involving the use of
      mitotically active chorionic villus tissue to prepare metaphase chromosome
      spreads directly, without cell culture. Two support protocols describe methods
      for collecting tissue samples.

PMID- 19170033
TI  - Clinical validity and clinical utility of genetic tests.
AB  - In considering the appropriate use of new genetic tests, clinicians and health
      care policymakers must consider the accuracy with which a test identifies a
      patient's clinical status (clinical validity) and the risks and benefits
      resulting from test use (clinical utility). Genetic tests in current use vary in
      accuracy and potential to improve health outcomes, and these test properties may
      be influenced by the clinical setting in which the test is used. This unit
      defines clinical validity and clinical utility, provides examples, and considers
      the implications of these test properties for clinical practice.

PMID- 19170034
TI  - Overview of pharmacogenetics.
AB  - Pharmacogenetics is the study of relationships between genetic variation and
      inter-individual differences with respect to drug response. As the field has
      matured over the past 15 years, a remarkable diversity of pathways, variation
      types, and mechanisms have been found to be relevant pharmacogenetic factors.
      Today, pharmacogenetics is becoming more important in pharmacology for target
      validation, lead optimization, and understanding of idiosyncratic toxicity. This
      unit provides an overview of the history of pharmacogenetics and current research
      applications in drug discovery, as well as a discussion of research quality
      issues relevant for human subjects research in the pharmacogenetics laboratory.

PMID- 19170035
TI  - Robust dosage PCR (RD-PCR) for highly accurate dosage analysis.
AB  - Clinical diagnostic and epidemiological assays would benefit from accurate
      detection of duplications and deletions commonly missed by conventional methods
      of polymerase chain reaction (PCR) amplification and sequencing of individual
      exons. Robust dosage-PCR (RD-PCR) is a quantitative PCR method that co-amplifies
      a target template and an endogenous internal control (an autosomal and an X
      chromosomal segment) for detection of these mutations. RD-PCR has the advantage
      of high accuracy and consistency, rapid assay development, widely available
      controls, and gene dosage over a wide dynamic range.

PMID- 19170036
TI  - Establishing and maintaining system linearity.
AB  - A flow cytometer system transforms a received optical signal into an electrical
      signal whose amplitude ideally is directly proportional to the optical signal but
      in practice is at least related in a linear fashion. Establishment and
      maintenance of system linearity are prerequisites to accurate quantitative
      measurements. The many potential sources of offsets and nonlinearity are found in
      all parts of the detection, amplification, and data acquisition systems of a flow
      instrument. This unit aims to help investigators evaluate performance of the
      hardware in flow cytometer detection systems.

PMID- 19170037
TI  - Measurement of cytoplasmic to nuclear translocation.
AB  - A method is described for the quantitative assessment of the translocation of
      signaling molecules from the cytoplasm to the nucleus in cells. This method
      utilizes fluorochrome-conjugated antibodies to the signaling molecule and a
      nuclear dye, and it is based on imagery acquired rapidly in flow with the use of
      a multispectral imaging cytometer. The analysis correlates the spatial
      distribution of the stained translocating signaling molecule with nuclear
      staining, and it generates a quantitative score for each cell using Pearson's
      correlation coefficient. Examples described in this section use reagents that
      detect NFkappaB and IRF-7 and measure the translocation of these molecules under
      stimulating conditions. A protocol for combining cell surface phenotype with
      cytoplasm to nuclear translocation is also included.

PMID- 19170038
TI  - Dependency and self-criticism in post-partum depression and anxiety: a case
      control study.
AB  - This study investigates the role of self-criticism and dependency in inpatient
      post-partum depressed women (n = 55) and non-depressed controls (n = 37) as well
      as the relationship between both personality dimensions and severity of
      depression and anxiety. As expected, mothers with post-partum depression showed
      not only increased levels of depression but also anxiety compared with non
      depressed mothers. Furthermore, they had significantly higher levels of self
      criticism, but not of dependency. In the post-partum depressed mothers, both
      personality dimensions were positively associated with severity of depression.
      However, in non-depressed mothers, self-criticism was positively associated with
      depression, while there was an inverse relationship between dependency and
      severity of depression. In both samples, self-criticism, but not dependency, was
      related to state anxiety. The cross-sectional nature of this study limits the
      ability to draw causal conclusions. The study was based on self-report and
      conducted in relatively small samples.

PMID- 19170039
TI  - Epitope mapping by amide hydrogen/deuterium exchange coupled with immobilization
      of antibody, on-line proteolysis, liquid chromatography and mass spectrometry.
AB  - The epitope of horse cytochrome c against monoclonal antibody E8 was determined
      using amide hydrogen/deuterium (H/D) exchange combined with immobilized antibody,
      on-line pepsin proteolysis, liquid chromatography (LC), and mass spectrometry
      (MS). The results were generally in good agreement with contact residues
      identified by an X-ray co-crystal structure of the E8-cytochrome c complex and
      results obtained by H/D exchange with nuclear magnetic resonance (NMR)
      spectrometry. The H/D exchange reaction of cytochrome c was carried out in the
      presence or absence of immobilized E8 antibody. Regions that gained less
      deuterium in the presence of the antibody than in its absence are defined as the
      epitope by the H/D exchange MS method. Control experiments were carefully
      designed to help identify the epitope with high confidence.

PMID- 19170040
TI  - Low glyphosate rates do not affect Citrus limonia (L.) Osbeck seedlings.
AB  - BACKGROUND: Glyphosate is used to control weeds in citrus orchards, and
      accidental spraying or wind drift onto the seedlings may cause growth arrest
      owing to metabolism disturbance. Two experiments were carried out to investigate
      the effect of non-lethal rates (0, 180, 360 and 720 g AI ha(-1)) of glyphosate on
      four-month-old 'Cravo' lime, Citrus limonia (L.) Osbeck, seedlings.
      Photosynthesis and the concentrations of shikimic acid, total free amino acids
      and phenolic acids were evaluated. RESULTS: Only transitory effects were observed
      in the contents of shikimate and total free amino acids. No visual effects were
      observed. CONCLUSION: The present study showed that glyphosate at non-lethal
      rates, which is very usual when accidental spraying or wind drift occurs in
      citrus orchard, did not cause severe metabolic damage in 'Cravo' lime seedlings.

PMID- 19170041
TI  - Older peoples' attitudes to mental illness.
AB  - Despite the prevalence of mental health problems in later life, older people
      markedly underutilize mental health services. A greater awareness of factors
      influencing older peoples' attitudes to mental illness may therefore improve
      awareness and treatment of mental disorders in this population. A mixed
      methodology approach was used to explore and compare older peoples' attitudes to
      mental illness in a sample of clinical and non-clinical participants. Results
      indicated that, similar to younger people, older people endorsed a range of
      positive and negative attitudes to mental illness. However, when attitudes to
      mental illness were considered within the context of ageing and experience a more
      complex pattern of results emerged. Although negative attitudes to mental illness
      were associated with negative attitudes to ageing across the entire sample,
      clinical participants (and those with prior experience of mental illness)
      reported more positive attitudes to mental illness and more negative attitudes to
      ageing than non-clinical participants, for whom the reverse was true. Attitudes
      were also differentially related to health behaviour outcomes. Results suggest
      that attitudes to mental illness and ageing may be linked and mediated by
      personal experience and capacity for psychological self-regulation in the face of
      age-associated adversity.

PMID- 19170042
TI  - Sexual recombination of carbendazim resistance in Fusarium graminearum under
      field conditions.
AB  - BACKGROUND: Carbendazim has been the major fungicide for control of Fusarium head
      blight (FHB) caused by Fusarium graminearum Schwade in China. However, the
      effectiveness of carbendazim has been threatened by the emergence of resistant
      pathogen populations in the field. RESULTS: Five isolates, representing three
      phenotypes of different carbendazim sensitivity levels (S, MR and HR), were
      randomly selected to study the inheritance of carbendazim resistance by three
      genetic crosses under field conditions. Each parent in all crosses was marked
      with a different class of nitrate non-utilizing (nit) mutation. The presence of
      sexual recombinants indicated that outcrossing had occurred in the crosses. Over
      100 putative self-crossing or outcrossing perithecia for each cross were randomly
      sampled on the surface of the haulms of dead rice for each pair of parents.
      Results showed that 5.7-20.9% outcrossing frequency occurred in the three crosses
      and confirmed sexual recombination under field conditions. There were no
      significant differences in mycelial linear growth and pathogenicity between the
      selected recombinants and their parents, but they differed in sporulation ability
      and capacity to produce perithecia. Nevertheless, most of the sexual recombinants
      possessed fitness levels comparable with those of their parents. CONCLUSION:
      Outcrossing between carbendazim-sensitive and -resistant isolates did occur under
      field conditions, and sexual recombination must play a role in the development of
      carbendazim resistance in the field.

PMID- 19170043
TI  - Anatomy and development of the nervous system of Nematostella vectensis, an
      anthozoan cnidarian.
AB  - Nematostella vectensis, an anthozoan cnidarian, whose genome has been sequenced
      and is suitable for developmental and ecological studies, has a complex neural
      morphology that is modified during development from the larval to adult form. N.
      vectensis' nervous system is a diffuse nerve net with both ectodermal sensory and
      effector cells and endodermal multipolar ganglion cells. This nerve net consists
      of several distinct neural territories along the oral-aboral axis including the
      pharyngeal and oral nerve rings, and the larval apical tuft. These neuralized
      regions correspond to expression of conserved bilaterian neural developmental
      regulatory genes including homeodomain transcription factors and NCAMs. Early
      neurons and stem cell populations identified with NvMsi, NvELAV, and NvGCM,
      indicate that neural differentiation occurs throughout the animal and initiates
      prior to the conclusion of gastrulation. Neural specification in N. vectensis
      appears to occur through an independent mechanism from that in the classical
      cnidarian model Hydra.

PMID- 19170044
TI  - Lymph node assessment and lymphadenectomy in prostate cancer.
AB  - The role of lymph node assessment for patients with clinically localized prostate
      cancer has significantly evolved over the last 20 years. The status of pelvic
      lymph nodes primarily served as a prognostic marker for prostate cancer. Improved
      methods in assessing the risk for cancer progression and metastasis have enhanced
      our ability to identify patients who require pelvic lymphadenectomy during
      radical prostatectomy. The status of pelvic lymph nodes is also being used to
      guide further treatments after surgery. Also, recent data has shown possible
      therapeutic benefit of lymphadenectomy in improving cancer specific survival.

PMID- 19170045
TI  - The role of lymphadenectomy in the management of papillary carcinoma of the
      thyroid.
AB  - Impact of nodal involvement in papillary thyroid cancer remains controversial.
      The incidence of nodal metastases is high and the presence of involved nodes has
      a negative impact on recurrence and possibly on survival as well, particularly in
      older patients. The risk of nodal disease increases with age, tumor size, and
      BRAF oncogene expression. Most thyroid surgeons sample the ipsilateral central
      nodes as a minimum and clear the central compartment if there is gross adenopathy
      present. Lateral compartment neck dissection is reserved for patients with known
      metastatic disease. This article attempts to review the literature on surgery of
      lymph nodes in papillary thyroid cancer.

PMID- 19170046
TI  - Quantitative and qualitative profiling of endocannabinoids in human plasma using
      a triple quadrupole linear ion trap mass spectrometer with liquid chromatography.
AB  - Owing to the large implication of endocannabinoids (ECs) in many physiological
      and pathophysiological processes, a rapid liquid chromatography/electrospray
      ionisation triple quadrupole linear ion trap mass spectrometric assay (LC/ESI
      QqQ(LIT)) was developed for the detection and characterization of anandamide
      (AEA), 2-arachidonoyl glycerol (2-AG), virodhamine (VA), noladin ether (2-AGE),
      and N-arachidonoyl dopamine (NADA) in human plasma. The ECs were extracted from
      500 microL of plasma by liquid-liquid extraction (LLE) and separated by using an
      XTerra C18 MS column (50 x 3.0 mm i.d., 3.5 microm) with gradient elution. The
      mobile phase was composed of a mixture of acetonitrile, water, and formic acid
      (0.1%). For confirmatory analysis, an information-dependent acquisition (IDA)
      experiment was performed with selected reaction monitoring (SRM) as survey scan
      and enhanced product ion (EPI) as dependent scan. The assay was found to be
      linear in the concentration range of 0.1-5 ng/mL for AEA, 0.3-5 ng/mL for VA, 2
      AGE, and NADA and 1-20 ng/mL for 2-AG using a 0.5 mL aliquot of plasma.
      Repeatability and intermediate precision were found less than 15% over the tested
      concentration ranges. The developed method thus provided the rapid, highly
      sensitive and highly selective requirement for assess quantitation, and
      identification of ECs in plasma.

PMID- 19170047
TI  - Commentary on 'Dementia: an anthropological perspective' by Mahnaz Hashmi.

PMID- 19170049
TI  - Malignancy arising in seminal vesicles in the transgenic adenocarcinoma of mouse
      prostate (TRAMP) model.
AB  - BACKGROUND: Transgenic adenocarcinoma of mouse prostate (TRAMP) mice, derived by
      prostate specific expression of SV40 large T antigen using the rat probasin
      promoter, all develop prostate tumors akin to human prostate cancers. More
      recently, epithelial-stromal (ES) tumors resembling phyllodes tumors have been
      described in the seminal vesicles of TRAMP mice. We report malignancy arising in
      these ES tumors of the seminal vesicles in TRAMP mice. METHODS: H&E stained
      sections from 28-week-old TRAMP mice autopsies were examined. Immunostains
      (cytokeratin, vimentin, desmin, and MIB-1) and electron microscopy were performed
      on selected blocks of the genitourinary system and metastatic tumor nodules.
      RESULTS: The seminal vesicles frequently develop tumors containing broad
      papillae, with bland epithelium and a cellular spindled stroma just beneath the
      epithelium. The stromal cells have high nuclear to cytoplasmic ratio, frequent
      apoptotic cells and mitoses. In some cases, the stromal cells become large mass
      lesions that overgrow the prostate. The epithelium can also proliferate and
      become malignant. The tumors have high proliferation indices by MIB-1. Some
      metastatic tumors have characteristics similar to the seminal vesicle ES tumor.
      CONCLUSIONS: Metastatic tumors in TRAMP mice show three patterns: (1) A definite
      adenocarcinoma pattern metastatic from the prostate; (2) poorly differentiated
      tumor without epithelial differentiation; (3) carcinosarcomatous pattern. The
      carcinosarcomatous pattern and some of the poorly differentiated tumors likely
      arise from seminal vesicle ES tumors.

PMID- 19170048
TI  - Protease-activated receptor-1 is upregulated in reactive stroma of primary
      prostate cancer and bone metastasis.
AB  - BACKGROUND: Prostate cancer progression is partly facilitated by tumor-stroma
      interactions. We recently reported that protease-activated receptors (PAR-1 and
      PAR-2) are overexpressed in prostate cancer, and PAR-1 expression in peritumoral
      stroma is associated with biochemical recurrence. However, the nature of PAR
      expression in prostate tumor microenvironment is not fully understood. We
      therefore evaluated PAR-1 and PAR-2 expression in primary prostate cancer and
      bone metastasis. METHODS: PAR-1 and PAR-2 expression in normal, primary prostate
      cancer and the corresponding bone metastatic tissues were examined by
      immunohistochemistry, and double-label immunohistochemistry with the use of
      additional markers. RESULTS: PAR-1 was expressed in peritumoral stroma in the
      majority of primary cancer tissues (83%). Serial sections and double-label
      immunohistochemistry determined that these PAR-1 expressing stromal cells were
      predominantly myofibroblasts, the primary cell type in reactive stroma. Analysis
      of cancer glands revealed that PAR-1 expression was significantly increased in
      the reactive stroma around higher Gleason grade cancers. PAR-2 was predominantly
      expressed in the primary cancer cells as well as smooth muscle cells but not in
      reactive stroma. In bone metastasis, PAR-1 expression in cancer cells was
      elevated compared to the primary site from the same patient. In the bone reactive
      stroma, PAR-1 was present in vascular endothelial cells and fibroblasts, while
      both PAR-1 and PAR-2 were expressed in osteoblasts and osteoclasts. CONCLUSIONS:
      In primary prostate cancer and bone metastasis, PAR-1 is upregulated in reactive
      stroma and PAR-2 is uniformly overexpressed in carcinoma cells, suggesting these
      receptors may play potentially different roles in prostate cancer development and
      metastasis.

PMID- 19170050
TI  - A small sample study of the STEPP approach to assessing treatment-covariate
      interactions in survival data.
AB  - A new, intuitive method has recently been proposed to explore treatment-covariate
      interactions in survival data arising from two treatment arms of a clinical
      trial. The method is based on constructing overlapping subpopulations of patients
      with respect to one (or more) covariates of interest and in observing the pattern
      of the treatment effects estimated across the subpopulations. A plot of these
      treatment effects is called a subpopulation treatment effect pattern plot. Here,
      we explore the small sample characteristics of the asymptotic results associated
      with the method and develop an alternative permutation distribution-based
      approach to inference that should be preferred for smaller sample sizes. We then
      describe an extension of the method to the case in which the pattern of estimated
      quantiles of survivor functions is of interest.

PMID- 19170052
TI  - On-line preconcentration and enantioseparation of thalidomide racemates by CEC
      with the hyphenation of octyl and norvancomycin monoliths.
AB  - A method was developed for simultaneous preconcentration and chiral separation of
      thalidomide enantiomers in human urine by CEC in combination with self
      concentration and solvent gradient effects. A 4 cm long octyl (C8) monolithic
      column was hyphenated with a 15 cm long norvancomycin (NVC)-bonded monolithic
      column via a fluorinated ethylene-propylene interface. Sample solution was
      injected into the C8 monolithic column, the two thalidomide enantiomers were
      first preconcentrated on the C8 monolithic column, and then separated with a
      further concentration on the NVC-bonded monolithic column by CEC. Injection of
      34.8 mm plug of sample solution gave 278- and 298-fold enhancement in
      sensitivity, and detection limits of 90 and 94 microg/L for the two thalidomide
      enantiomers. Peak areas of the two isomers were linear in a range of 0.5-50 mg/L.
      The precision for five replicate injections of 10 mg/L were 0.8-0.9 and 1.1-2.3%
      for the migration time and peak height, respectively. The developed method was
      applied to the determination of racemic thalidomide in spiked human urine
      samples.

PMID- 19170051
TI  - Mechanical control of cAMP signaling through integrins is mediated by the
      heterotrimeric Galphas protein.
AB  - Mechanical stresses that are preferentially transmitted across the cell surface
      via transmembrane integrin receptors activate gene transcription by triggering
      production of intracellular chemical second messengers, such as cAMP. Here we
      show that the sensitivity of the cAMP signaling pathway to mechanical stresses
      transferred across beta1 integrins is mediated by force-dependent activation of
      the heterotrimeric G protein subunit Galphas within focal adhesions at the site
      of stress application. Galphas is recruited to focal adhesions that form within
      minutes following clustering of beta1 integrins induced by cell binding to
      magnetic microbeads coated with activating integrin ligands, and beta1 integrin
      and Galphas co-precipitate when analyzed biochemically. Stress application to
      activated beta1 integrins using magnetic twisting cytometry increases Galphas
      recruitment and activates these large G proteins within focal adhesions, as
      measured by binding of biotinylated azido-anilido-GTP, whereas application of
      similar stresses to inactivated integrins or control histocompatibility antigens
      has little effect. This response is relevant physiologically as application of
      mechanical strain to cells bound to flexible extracellular matrix-coated
      substrates induce translocation of phospho-CREB to the nucleus, which can be
      attenuated by inhibiting Galphas activity, either using the inhibitor melittin or
      suppressing its expression using siRNA. Although integrins are not typical G
      protein-coupled receptors, these results show that integrins focus mechanical
      stresses locally on heterotrimeric G proteins within focal adhesions at the site
      of force application, and transduce mechanical stimuli into an intracellular cAMP
      signaling response by activating Galphas at these membrane signaling sites.

PMID- 19170053
TI  - CEC column behaviour of butyl and lauryl methacrylate monoliths prepared in non
      aqueous media.
AB  - Polymeric monolithic stationary phases for capillary electrochromatography were
      prepared using two bulk monomers, butyl methacrylate (BMA) and lauryl
      methacrylate (LMA), by in situ polymerization in non-aqueous media. The effect of
      1,4-butanediol/1-propanol ratio on porous properties was investigated separately
      for each monomer, keeping the proportion of monomers to pore-forming solvents
      fixed at 40:60 wt:wt. Also, mixtures of BMA and LMA at different 1,4-butanediol/1
      propanol ratios were studied for tailoring the morphological features of the
      monolithic columns. The chromatographic performance of the different columns was
      evaluated by means of van Deemter plots of polycyclic aromatic hydrocarbons.
      Mercury-intrusion porosimetry, SEM, and nitrogen-adsorption measurements were
      also performed in order to understand their retention behaviour and porous
      properties. A comparison of these features was also performed for monoliths made
      with one bulk monomer (BMA or LMA) and with mixtures of both. These mixed
      monoliths showed satisfactory efficiencies and analysis times compared with those
      made with one bulk monomer; thus, the BMA-LMA monoliths constitute an attractive
      alternative to manipulate the electrochromatographic properties of methacrylate
      beds in CEC.

PMID- 19170054
TI  - Novel negatively charged tentacle-type polymer coating for on-line
      preconcentration of proteins in CE.
AB  - A novel negatively charged tentacle-type polymer-coated capillary column was
      fabricated and applied for on-line extraction and preconcentration of proteins.
      The polymer coating was prepared by glycidyl-methacrylate graft polymerization in
      a silanized capillary column and the following sulfonic acid group
      functionalization. It had high surface area and offered high phase ratio for
      protein adsorption. In addition, the polymer-coated capillary column provided
      more stable EOF than a bare uncoated capillary. These features of the polymer
      coating facilitated the extraction of proteins through electrostatic
      interactions. This was used to extract proteins. The extracted analytes were then
      desorbed and focused by EOF in the direction opposite to the sample injection
      flow for subsequent CE. With this procedure, over 1500-fold sensitivity
      enhancement was realized for myoglobin (MB) as compared with a normal capillary
      zone electrophoresis. By comparison of the peak areas of the enriched protein, it
      was found that the polymer-coated column could capture proteins about 30 times
      more than the uncoated column. In addition, the separation of a protein mixture
      containing 0.4 microg/mL of MB and 0.4 microg/mL of insulin was demonstrated by
      the on-line preconcentration and electrophoretic separation with the polymer
      coated column.

PMID- 19170055
TI  - Simultaneous determination of galantamine, rivastigmine and NAP 226-90 in plasma
      by MEKC and its application in Alzheimer's disease.
AB  - A simple and sensitive MEKC with UV detection was developed and validated for the
      simultaneous determination of acetylcholinesterase inhibitors including
      galantamine, rivastigmine and major metabolite NAP 226-90 in plasma. A sample
      pretreatment by liquid-liquid extraction with diethylether and subsequent
      quantification by MEKC was used. The optimum separation for these analytes was
      achieved in <10 min at 25 degrees C with a fused-silica capillary column of 30.2
      cm x 50 microm id (effective length 20 cm) and a run buffer containing 25 mM Tris
      buffer (pH 5.0) with 160 mM sodium octanesulfonate, 20% ACN and 0.01% PVP as a
      dynamic coating to reduce analytes' interaction with the capillary wall. For
      sensitivity consideration regarding the determination of linearity, LOD,
      quantitation and monitoring drugs concentration in patients, the detection
      wavelengths for galantamine or rivastigmine and NAP 226-90 were set at 214 or 200
      nm, respectively. One male volunteer (26-year-old) was orally administered a
      single dose of 4.5 mg rivastigmine (Exelon, Novartis) in capsule, and blood
      samples were drawn over a 12 h period for concentration-time profile study. The
      method was also successfully applied for monitoring galantamine or rivastigmine
      and its metabolite NAP 226-90 in 11 Alzheimer's disease patients' plasma after
      oral administration of the commercial products Reminyl (8 mg galantamine/capsule)
      or Exelon (3 mg rivastigmine/capsule), respectively.

PMID- 19170056
TI  - Low cost, portable detection of gold nanoparticle-labeled microfluidic
      immunoassay with camera cell phone.
AB  - This paper describes the use of camera cell phone to detect the gold nanoparticle
      labeled immunoassay results on microfluidic chip. On-chip heterogeneous
      immunoassay between anti-human IgG and human IgG (hIgG) was performed and the
      results were amplified by gold nanoparticle-enhanced silver staining to transform
      the nano-scale probe into detectable silver precipitation film. The detection
      results obtained by camera phone showed good correlation with the concentration
      of hIgG. This detection scheme is simple, low cost and easy to use and has
      significant promise for portable diagnosis and point of care testing on
      microfluidic platform.

PMID- 19170057
TI  - Chemical initiation for butyl and lauryl acrylate monolithic columns for CEC.
AB  - Butyl acrylate (BA)- and lauryl acrylate (LA)-based monolithic stationary phases
      for CEC were synthesized, using a redox system as initiator of polymerization. BA
      monoliths were initiated with ammonium peroxodisulfate, whereas LA columns were
      obtained with lauroyl peroxide as initiator. In both cases, TEMED was used to
      activate the process. The influence of porogenic solvent composition on both
      morphological and electrochromatographic properties of the resulting monoliths
      was investigated. Excellent efficiencies (minimum plate heights of 4.2-6.3 microm
      for BA columns and 2.6-5.3 microm for LA stationary phases, for a PAHs mixture)
      were achieved. The capability of separation of both types of monolithic beds was
      compared by the analysis of complex mixtures of polycyclic aromatic hydrocarbons
      and anabolic steroids.

PMID- 19170058
TI  - IFI16 and NM23 bind to a common DNA fragment both in the P53 and the cMYC gene
      promoters.
AB  - In the melanoma M14 cell line, we found that the antimetastatic protein
      NM23/nucleoside diphosphate kinase binds to the promoters of the oncogene cMYC
      and of P53, a gene often mutated in human cancer (Cervoni et al. [2006] J. Cell.
      Biochem. 98:421-428). In a further study, we find now that IFI16, a
      transcriptional repressor, in both promoters binds to the G-rich fragment that
      also binds NM23/NDPK. These fragments possess non-B DNA structures. Moreover, by
      sequential chromatin immunoprecipitation (re-ChIP) we show that the two proteins
      (IFI16 and NM23/NDPK) are simultaneously bound in vivo to the same DNA fragments.
      Since P53 stimulates apoptosis and inhibits cellular growth, and cMYC promotes
      cell growth and, in several instances, also apoptosis, the presence of NM23 and
      IFI16 on the same DNA fragments suggests their common involvement in the reduced
      development of some tumors.

PMID- 19170059
TI  - Nerve growth factor promotes differentiation of odontoblast-like cells.
AB  - Contemporary strategies in tooth repair markedly rely on the newest findings on
      the cellular and biological components of dental development. Among several
      identified bioactive molecules, neurotrophins were recently proposed to affect
      tooth germ cell proliferation, differentiation, and cell-extracellular matrix
      interactions. The present study attempted to explore the effect of nerve growth
      factor (NGF) on a spontaneously immortalized dental papilla mesenchymal cell
      line. NGF induced differentiation of odontoblast-lineage cells with subsequent
      biomineralization in vitro. Here we showed that normalized transcript levels of
      tissue-specific markers such as DSPP and DMP1 were elevated significantly,
      indicating cell differentiation and maturation processes. We performed innovative
      gene expression analysis of TM14, a matricellular protein and novel member of the
      fibulin family. TM14 expression followed a pattern similar to that of DMP1, which
      suggests its important role in cell-matrix and intercellular interactions during
      dentin calcification. Alkaline phosphatase enzyme assay confirmed the
      extracellular matrix calcifications in NGF-supplemented groups. Thus, NGF was
      characterized as a potent promoter of mineralization during dentin formation. For
      the first time, we included TM14 in odontoblast genotype analysis and proved that
      NGF also promotes in vitro odontoblast differentiation. Collectively, these
      results highlight the importance of NGF during tooth morphogenesis, as well as
      urge the elaboration of complex epithelial-mesenchymal tissue cultures, where
      further elucidation of the signaling factor network could be completed.

PMID- 19170060
TI  - Hemin promotes proliferation and differentiation of endothelial progenitor cells
      via activation of AKT and ERK.
AB  - Increased neovascularization is commonly observed in hemorrhagic plaques and
      associated with rupture of atherosclerotic lesions. This study aims to
      investigate whether hemin accumulated at the site of hematoma promotes
      neovascularization through affecting the growth and function of endothelial
      progenitor cells (EPCs) and the possible mechanism involved. Here we demonstrated
      that hemin promoted a significant increase in neovessel formation in matrigel
      plugs embedded in vivo and enhanced the proliferation and endothelial gene
      expression in EPCs in vitro. VEGF-induced migration response and the capability
      to incorporate into the vascular networks were markedly enhanced in hemin-treated
      EPCs. Hemin induced the phosphorylation of ERK and AKT but not p38 or JNK. The
      inhibition of AKT or ERK activation significantly attenuated the effect of hemin
      on cell proliferation. However, the enhanced migration response induced by hemin
      was significantly suppressed by the inhibition of AKT but not ERK. Hemin induced
      significant increase in reactive oxygen species (ROS) production and hemin
      induced angiogenic response of EPCs was substantially reduced by treatment with N
      acetylcysteine. Collectively, these data support that hemin-induced ROS mediates
      the activation of AKT and ERK signaling pathways, which in turn promotes the cell
      proliferation and function of EPCs. J. Cell. Physiol. 219: 617-625, 2009. (c)
      2009 Wiley-Liss, Inc.

PMID- 19170061
TI  - Gastrointestinal pathology in a mouse model of mucopolysaccharidosis type IIIA.
AB  - Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder caused
      by a deficiency in sulphamidase (NS), a lysosomal enzyme required for the
      degradation of heparan sulphate glycosaminoglycans (gags). The MPS IIIA mouse is
      a naturally occurring model that accurately reflects the human pathology and
      disease course. It displays primarily central nervous system pathology
      accompanied by widespread accumulation of gag in somatic tissues. MPS IIIA mice
      exhibit greater bodyweight gain than normal littermates and attain a higher
      mature bodyweight. In this study, gastrointestinal morphology and function was
      characterised in the IIIA mouse. Stomach and duodenum weight increased in MPS
      IIIA mice and duodenum length also increased. An increased submucosal thickness
      was observed in MPS IIIA intestine compared to normal mice and lysosomal storage
      of gag was observed in this region. Storage was also observed in the lamina
      propria of the villus tip. All other morphometric measurements including villus
      height and crypt depth fell within the normal range. The gastric emptying half
      life of solid and liquid meals decreased with age in normal mice whereas the
      T(1/2) of solid meals did not alter with age in MPS IIA mice such that they were
      elevated above normal by 38 weeks of age. Sucrase activity was higher than normal
      in MPS IIIA at all ages tested. These abnormalities in GI structure and function
      observed in MPS IIIA may contribute to weight gain in this disorder.

PMID- 19170062
TI  - Critical role of the N-terminal cyclic AMP-binding domain of Epac2 in its
      subcellular localization and function.
AB  - cAMP is a well-known regulator of exocytosis, and cAMP-GEFII (Epac2) is involved
      in the potentiation of cAMP-dependent, PKA-independent regulated exocytosis in
      secretory cells. However, the mechanisms of its action are not fully understood.
      In the course of our study of Epac2 knockout mice, we identified a novel splicing
      variant of Epac2, which we designate Epac2B, while renaming the previously
      identified Epac2 Epac2A. Epac2B, which lacks the first cAMP-binding domain A in
      the N-terminus but has the second cAMP-binding domain B of Epac2A, possesses GEF
      activity towards Rap1, as was found for Epac2A. Immunocytochemical analysis
      revealed that exogenously introduced Epac2A into insulin-secreting MIN6 cells was
      localized near the plasma membrane, while Epac2B was found primarily in the
      cytoplasm. Interestingly, cAMP-binding domain A alone introduced into MIN6 cells
      was also localized near the plasma membrane. In MIN6 cells, Epac2A was involved
      in triggering hormone secretion by stimulation with 5.6 mM glucose plus 1 mM 8
      Bromo-cAMP, but Epac2B was not. The addition of a membrane-targeting signal to
      the N-terminus of Epac2B was able to mimic the effect of Epac2A on hormone
      secretion. Thus, the present study indicates that the N-terminal cAMP-binding
      domain A of Epac2A plays a critical role in determining its subcellular
      localization and potentiating insulin secretion by cAMP. J. Cell. Physiol. 219:
      652-658, 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19170063
TI  - FGF8 regulates myogenesis and induces Runx2 expression and osteoblast
      differentiation in cultured cells.
AB  - In the current study, treatment of the rat osteogenic cell line ROB-C26 cells
      with fibroblast growth factor 8 (FGF8) stimulated alkaline phosphatase (ALP)
      activity, and also induced the expression of the Runx2 transcription factor, and
      increased the activity of a luciferase reporter gene containing the osteocalcin
      (OCN) promoter and six copies of the osteoblast specific cis-acting element 2
      (OSE2) response element. In contrast, FGF8 treatment of the mouse myoblast cell
      line C2C12 inhibited the expression of desmin and the synthesis of myotubes. The
      expression of MyoD, Myogenin, Foxc2, and Hand1 was also decreased by FGF8.
      Transient expression of Foxc2 in C2C12 cells induced the expression of Hand1, and
      chromatin immunoprecipitation (ChIP) analysis indicated that Foxc2 binds to the
      promoter region of the Hand1 gene. These results indicated that Foxc2 is directly
      involved in the regulation of Hand1 expression. The results of the current study
      indicate that FGF8 regulates myoblast differentiation through the regulation of
      MyoD expression, and that this regulation is independent of Hand1 in cultured
      cells. Conversely, FGF8 supports bone development and cell differentiation though
      the induction of Runx2 expression.

PMID- 19170064
TI  - Prolactin's role in the early stages of liver regeneration in rats.
AB  - Liver regeneration after partial hepatectomy (PHx) is a complex process that is
      regulated by hemodynamic changes, the modulation of cytokines and growth factors,
      and the activation of immediate early transcription factors that lead to a round
      of hepatocyte mitosis. Among the factors involved, the pituitary hormone
      prolactin (PRL) has been shown to induce a hepatotrophic response after partial
      hepatectomy similar to that caused by phorbol esters; and in isolated hepatocytes
      PRL triggers a mitogenic response. However, it is becoming clear that PRL exerts
      a dual role acting in proliferation and differentiation processes. In this work,
      we have assessed the role of PRL in the early stages of liver regeneration in
      rats. To this end, three groups of rats were compared: Sham operated, regenerant
      and regenerant with PRL i.p. administration. Results show that PRL administration
      prior to partial hepatectomy caused an increase in the binding activity of
      several transcription factors involved in cell proliferation: AP-1, c-Jun and
      STAT-3, and in liver-specific differentiation and maintenance of energetic
      metabolism: CEBPalpha, HNF-1, HNF-4 at early time points and at later time points
      HNF-3. Hepatic sections show that PRL administration increases the number of
      proliferating cells within 5 h post-partial hepatectomy. The mRNA of the
      angiogenic and survival factors VEGF and HIF-1alpha, was also induced by PRL
      treatment. Data indicate that PRL triggers, either directly or indirectly, an
      acceleration of liver regeneration, preserving liver function and fulfilling a
      hepatoprotective role. J. Cell. Physiol. 219: 626-633, 2009. (c) 2009 Wiley-Liss,
      Inc.

PMID- 19170065
TI  - Analysis of energy stabilization inside the hydrophobic core of rubredoxin.
AB  - The hydrophobic core of globular proteins is responsible for major stabilization
      of the protein tertiary structure. The prevailing amino-acid residues in the core
      are of aliphatic or aromatic character, and therefore, the core in a folded
      protein structure is mostly stabilized by noncovalent interactions of van der
      Waals origin between the amino-acid side chains. Herein, we present a theoretical
      analysis of the interaction energy between the amino acids of the hydrophobic
      core of the small globular protein rubredoxin (Rd) based on the symmetry-adapted
      perturbation theory (SAPT) method. The results show uniform proportions between
      the second-order dispersion and first-order electrostatic energy terms in favor
      of dispersion interaction, which plays a major role in the stabilization of this
      important structural element. To demonstrate the contrast between systems
      stabilized by different mechanisms, we perform a SAPT analysis of the typical
      hydrogen bonds involved in the formation of protein secondary structure elements
      in Rd, where dispersion still plays a non-negligible role but electrostatic
      energy is the major stabilizing factor.

PMID- 19170066
TI  - Applying the inductive effect for synthesizing low-melting and low-viscosity
      imidazolium-based ionic liquids.
AB  - Fluidizing ionic liquids: By applying the inductive effect, a synthesis strategy
      to introduce strong, directional and localized H-bonds into imidazolium-based
      ionic liquids is proposed. In opposite to H-bonded molecular liquids these strong
      H-bonds could reduce the melting points and decrease the viscosities of the ILs
      (see figure).

PMID- 19170067
TI  - Recent approaches to antifungal therapy for invasive mycoses.
AB  - Invasive fungal infections with primary and opportunistic mycoses have become
      increasingly common in recent years and pose a major diagnostic and therapeutic
      challenge. They represent a major area of concern in today's medical fraternity.
      The occurrence of invasive fungal diseases, particularly in AIDS and other
      immunocompromised patients, is life-threatening and increases the economic
      burden. Apart from the previously known polyenes and imidazole-based azoles,
      newly discovered triazoles and echinocandins are more effective in terms of
      specificity, yet some immunosuppressed hosts are difficult to treat. The main
      reasons for this include antifungal resistance, toxicity, lack of rapid and
      microbe-specific diagnoses, poor penetration of drugs into sanctuary sites, and
      lack of oral or intravenous preparations. In addition to combination antifungal
      therapy, other novel antimycotic treatments such as calcineurin signaling pathway
      blockers and vaccines have recently emerged. This review briefly summarizes
      recent developments in the pharmacotherapeutic treatment of invasive fungal
      infections.

PMID- 19170068
TI  - Copolymerization of divinylsilyl-11-silicotungstic acid with butyl acrylate and
      hexanediol diacrylate: synthesis of a highly proton-conductive membrane for fuel
      cell applications.
AB  - Highly conducive to high conductivity: Polyoxometalates were incorporated in the
      backbone of a hydrocarbon polymer to produce proton-conducting films. These first
      generation materials contain large, dispersed clusters of polyoxometalates.
      Although the morphology of these films is not yet optimal, they already
      demonstrate practical proton conductivities and proton diffusion within the
      clusters appears to be very high.

PMID- 19170069
TI  - Formation of cross-linked chloroperoxidase aggregates in the pores of
      mesocellular foams: characterization by SANS and catalytic properties.
AB  - No escape: The formation of cross-linked chloroperoxidase aggregates (CPO-CLEAs)
      in the pores of mesocellular foam materials results in active biocatalysts that
      are more resistant to leaching than the conventional catalyst prepared by
      physisorption of chloroperoxidase. Small-angle neutron scattering (SANS)
      experiments clearly confirm that the CPO-CLEAs are located in the pores of the
      mesocellular foams.

PMID- 19170070
TI  - p53-mediated regulation of cell cycle progression: pronounced impact of cellular
      microenvironment.
AB  - Data on the biological effects of some overexpressed oncogenes and their
      cooperation with cellular factors are, at least partially, contradictory. There
      are reports on the strong pro-apoptotic action of temperature-sensitive (ts)
      p53(135val) in transformed cells at permissive temperature. However, in our
      experience very high levels of p53(135val) induce in transformed rat cells at
      permissive temperature cell cycle arrest but not apoptosis. Comparison of the
      experimental protocols reveals that cells used for transfection strongly differ.
      Therefore, we decided to explore the impact of primary cells used for generation
      of cell clones on the biological effects evoked by p53 and c-Ha-Ras. In the
      present study, we used primary rat cells (RECs) isolated from rat embryos of
      different age: at 13.5 gd (y) and 15.5 gd (o). We immortalized rat cells using ts
      p53(135val) mutant and additionally generated transformed cells after co
      transfection with oncogenic Ras. The RECs were transfected with a constitutively
      activated Ha-Ras protein, a mutation that is found in a wide variety of human
      tumors. The ts p53(135Val) mutant, switching between wild-type (wt) and mutant
      conformation, offers the possibility to study the escape from p53-mediated cell
      cycle control in a model of malignant transformation in cells with the same
      genetic background. Surprisingly, the kinetics of cell proliferation at non
      permissive temperature and that of cell cycle arrest at 32 degrees C strongly
      differed between cell clones established from yRECs and oRECs, thereby indicating
      that overexpression of genes such as ts p53(135Val) mutant and oncogenic-Ha-Ras
      does not fully override the intrinsic cellular program.

PMID- 19170072
TI  - Proton spectroscopic imaging of the human prostate at 7 T.
AB  - The sensitivity of proton MR Spectroscopic Imaging ((1)H-MRSI) of the prostate
      can be optimized by using the high magnetic field strength of 7 T in combination
      with an endorectal coil. In the work described in this paper we introduce an
      endorectal transceiver at 7 T, validate its safety for in vivo use and apply a
      pulse sequence, optimized for three-dimensional (3D) (1)H-MRSI of the human
      prostate at 7 T. A transmit/receive endorectal RF coil was adapted from a
      commercially available 3 T endorectal receive-only coil and validated to remain
      within safety guidelines for radiofrequency (RF) power deposition using numerical
      models, MR thermometry of phantoms, and in vivo temperature measurements. The
      (1)H-MRSI pulse sequence used adiabatic slice selective refocusing pulses and
      frequency-selective water and lipid suppression to selectively obtain the
      relevant metabolite signals from the prostate. Quantum mechanical simulations
      were used to adjust the inter-pulse timing for optimal detection of the strongly
      coupled spin system of citrate resulting in an echo time of 56 ms. Using this
      endorectal transceiver and pulse sequence with slice selective adiabatic
      refocusing pulses, 3D (1)H-MRSI of the human prostate is feasible at 7 T with a
      repetition time of 2 s. The optimized inter-pulse timing enables the absorptive
      detection of resonances of spins from spermine and citrate in phase with creatine
      and choline. These potential tumor markers may improve the in vivo detection,
      localization, and assessment of prostate cancer.

PMID- 19170071
TI  - Cytotoxicity induced by inhibition of thioredoxin reductases via multiple
      signaling pathways: role of cytosolic phospholipase A(2)alpha-dependent and 
      independent release of arachidonic acid.
AB  - The thioredoxin (Trx) system, comprising Trx, the selenoprotein thioredoxin
      reductase (TrxR), and NADPH, functions as an antioxidant system. Trx has various
      biological activities including growth control and anti-apoptotic properties, and
      the Trx system offers a target for the development of drugs to treat and/or
      prevent cancer. We evaluated the role of TrxR inhibition in the release of
      arachidonic acid (AA), cell toxicity, and intracellular signaling pathways in
      L929 mouse fibrosarcoma cells. Treatment with 1-chloro-2,4-dinitrobenzene (DNCB,
      an inhibitor of TrxR) under conditions involving limited inhibition of TrxR
      activity in cells, released AA before causing cytotoxicity. Treatment with an
      inhibitor of p38 kinase, a downstream enzyme of the apoptosis signal-regulating
      kinase 1 pathway, and pyrrophenone (an inhibitor of alpha-type cytosolic
      phospholipase A(2), cPLA(2)alpha) partially but significantly decreased the DNCB
      induced release of AA and cell death. The responses were much weaker in
      cPLA(2)alpha knockdown L929 cells. Exogenously added AA showed cytotoxicity. DNCB
      increased intracellular reactive oxygen species (ROS) levels, and butylated
      hydroxyanisole (an antioxidant) reduced DNCB-induced ROS formation and cell
      toxicity but not the phosphorylation of p38 kinase and release of AA. Auranofin,
      another inhibitor of TrxR having a different formula, released AA resulting in
      toxicity in L929 cells. DNCB caused the release of AA and cytotoxicity in A549
      human lung carcinoma cells, and caused p38 kinase-dependent toxicity in PC12 rat
      pheochromocytoma cells. Our data suggest that a dysfunctional Trx system triggers
      multiple signaling pathways, and that the AA released by cPLA(2)alpha-dependent
      and -independent pathways is important to cytotoxicity. J. Cell. Physiol. 219:
      606-616, 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19170073
TI  - Lack of lymphatic vessel phenotype in LYVE-1/CD44 double knockout mice.
AB  - Lymphatic vessels play a key role in maintaining tissue-fluid homeostasis, immune
      surveillance and metastasis. The hyaluronan receptor, LYVE-1, is widely used as a
      molecular marker for adult and embryonic lymphatic endothelium, but its
      physiological functions have not yet been established in vivo. In agreement with
      a recent report, LYVE-1(-/-) mice, which are healthy and fertile, do not display
      any defects related to congenital abnormalities of the lymphatic system. One
      hypothesis for the absence of a phenotype in LYVE-1 null mice is that other
      hyaluronan receptors, such as CD44, may compensate for LYVE-1. To test this
      hypothesis, we created LYVE-1/CD44 double knockout mice with appropriate
      littermate controls. Lymphatic vessel structure and function, as determined by
      histological methods and intravital microscopy, show that LYVE-1(-/-), CD44(-/-)
      and LYVE-1(-/-)/CD44(-/-) mice are indistinguishable from wild-type mice under
      normal conditions. Furthermore, resolution of carrageenan-induced paw edema is
      comparable in all genotypes. However, LYVE-1(-/-)/CD44(-/-) mice exhibit
      increased edema formation in a carrageenan-induced paw inflammation model
      compared to wild-type mice, but not to LYVE(-/-) or CD44(-/-) mice. These data
      suggest that LYVE-1 and CD44 are not required for the formation or function of
      lymphatics, but do not rule out a role for LYVE-1 in inflammation.

PMID- 19170074
TI  - Secretome from mesenchymal stem cells induces angiogenesis via Cyr61.
AB  - It is well known that bone marrow-derived mesenchymal stem cells (MSCs) are
      involved in wound healing and regeneration responses. In this study, we globally
      profiled the proteome of MSCs to investigate critical factor(s) that may promote
      wound healing. Cysteine-rich protein 61 (Cyr61) was found to be abundantly
      present in MSCs. The presence of Cyr61 was confirmed by immunofluorescence
      staining and immunoblot analysis. Moreover, we showed that Cyr61 is present in
      the culture medium (secretome) of MSCs. The secretome of MSCs stimulates
      angiogenic response in vitro, and neovascularization in vivo. Depletion of Cyr61
      completely abrogates the angiogenic-inducing capability of the MSC secretome.
      Importantly, addition of recombinant Cyr61 polypeptides restores the angiogenic
      activity of Cyr61-depleted secretome. Collectively, these data demonstrate that
      Cyr61 polypeptide in MSC secretome contributes to the angiogenesis-promoting
      activity, a key event needed for regeneration and repair of injured tissues. J.
      Cell. Physiol. 219: 563-571, 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19170075
TI  - Prostate cancer promotes CD11b positive cells to differentiate into osteoclasts.
AB  - Bone is the preferred site of prostate cancer metastasis, contributing to the
      morbidity and mortality of this disease. A key step in the successful
      establishment of prostate cancer bone metastases is activation of osteoclasts
      with subsequent bone resorption causing the release of several growth factors
      from the bone matrix. CD11b+ cells in bone marrow are enriched for osteoclast
      precursors. Conditioned media from prostate cancer PC-3 cells induces CD11b+
      cells from human peripheral blood to differentiate into functional osteoclasts
      with subsequent bone resorption. Analysis of PC-3 conditioned media revealed high
      amounts of IL-6 and IL-8. CD11b+ cells were cultured with M-CSF and RANKL, IL-6,
      IL-8, and CCL2, alone or in combination. All of these conditions induced
      osteoclast fusion, but cells cultured with M-CSF, IL-6, IL-8, and CCL2 were
      capable of limited bone resorption. Co-incubation with IL-6 and IL-8 and the RANK
      inhibitor, RANK-Fc, failed to inhibit osteoclast fusion and bone resorption,
      suggesting a potential RANKL-independent mechanism of functional osteoclast
      formation. This study demonstrates that functional osteoclasts can be derived
      from CD11b+ cells derived from human PBMCs. Prostate cancer cells secrete
      factors, including IL-6 and IL-8, that play an important role in osteoclast
      fusion by a RANKL-independent mechanism.

PMID- 19170077
TI  - CCCTC-binding factor meets poly(ADP-ribose) polymerase-1.
AB  - CCCTC-binding factor (CTCF) is a ubiquitous Zn-finger-containing protein with
      numerous recognized functions, including, but not limited to, gene activation and
      repression, enhancer-blocking, X-chromosome inactivation, and gene imprinting. It
      is believed that the protein performs such a variety of functions by interacting
      with an array of very diverse proteins. In addition, CTCF undergoes several post
      translational modifications, including poly(ADP-ribosyl)ation. The PARylated form
      of CTCF has recently been implicated in two important functions: gene imprinting
      and control of ribosomal gene transcription. Here, we summarize and critically
      discuss the available data on the interplay between CTCF and poly(ADP
      ribosyl)ation in these two processes. We consider the newly described phenomena
      in the broader context of PARP's activities, including the crucial role of
      protein PARylation in the regulation of the genome methylation pattern.

PMID- 19170078
TI  - Perfusion affects the tissue developmental patterns of human mesenchymal stem
      cells in 3D scaffolds.
AB  - Human mesenchymal stem cells (hMSCs) developed in three-dimensional (3D)
      scaffolds are significantly affected by culture conditions. We hypothesized that
      the hydrodynamic forces generated in perfusion bioreactors significantly affected
      hMSC functionality in 3D scaffolds by shaping the extracellular matrix (ECM)
      proteins. In this study, hMSCs were grown in 3D poly(ethylene terephthalate)
      (PET) scaffolds in static and a parallel perfusion system under similar initial
      conditions for up to 35 days. Results demonstrated that even at very low media
      velocities (O [10(-4) cm/sec]), perfusion cultures affected the ability of hMSCs
      to form an organized ECM network as illustrated by the immunostaining of collagen
      I and laminin fibrous structure. The change in the ECM microenvironment
      consequently influenced the nuclear shape. The hMSCs grown at the lower surface
      of static culture displayed a 15.2 times higher nuclear elongation than those at
      the upper surface, whereas cells grown in the perfusion bioreactor displayed
      uniform spherical nuclei on both surfaces. The difference in ECM organization and
      nuclear morphology associated with gene expression and differentiation
      characteristics of hMSCs. The cells exhibited lower CFU-F colony forming ability
      and decreased expressions of stem-cell genes of Rex-1 and Oct-4, implying a less
      primitive stem-cell phenotype was maintained in the perfusion culture relative to
      the static culture conditions. The significantly higher expression level of
      osteonectin gene in the perfusion culture at day 28 indicated an upregulation of
      osteogenic ability of hMSCs. The study highlights the critical role of dynamic
      culture conditions on 3D hMSC construct development and properties.

PMID- 19170076
TI  - Phytoestrogens regulate mRNA and protein levels of guanine nucleotide-binding
      protein, beta-1 subunit (GNB1) in MCF-7 cells.
AB  - Phytoestrogens (PEs) are non-steroidal ligands, which regulate the expression of
      number of estrogen receptor-dependent genes responsible for a variety of
      biological processes. Deciphering the molecular mechanism of action of these
      compounds is of great importance because it would increase our understanding of
      the role(s) these bioactive chemicals play in prevention and treatment of
      estrogen-based diseases. In this study, we applied suppression subtractive
      hybridization (SSH) to identify genes that are regulated by PEs through either
      the classic nuclear-based estrogen receptor or membrane-based estrogen receptor
      pathways. SSH, using mRNA from genistein (GE) treated MCF-7 cells as testers,
      resulted in a significant increase in GNB1 mRNA expression levels as compared
      with 10 nM 17beta estradiol or the no treatment control. GNB1 mRNA expression was
      up regulated two- to fivefold following exposure to 100.0 nM GE. Similarly, GNB1
      protein expression was up regulated 12- to 14-fold. GE regulation of GNB1 was
      estrogen receptor-dependent, in the presence of the anti-estrogen ICI-182,780,
      both GNB1 mRNA and protein expression were inhibited. Analysis of the GNB1
      promoter using ChIP assay showed a PE-dependent association of estrogen receptor
      alpha (ERalpha) and beta (ERbeta) to the GNB1 promoter. This association was
      specific for ERalpha since association was not observed when the cells were co
      incubated with GE and the ERalpha antagonist, ICI. Our data demonstrate that the
      levels of G-protein, beta-1 subunit are regulated by PEs through an estrogen
      receptor pathway and further suggest that PEs may control the ratio of alpha
      subunit to beta/gamma-subunits of the G-protein complex in cells. J. Cell.
      Physiol. 219: 584-594, 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19170079
TI  - Religiosity, spirituality, and psychological distress in African-Americans at
      risk for having a hereditary cancer predisposing gene mutation.
AB  - Elevated psychological distress has been observed among people at increased risk
      for familial cancer. Researchers consider religiosity and spirituality (RS) to be
      positive coping mechanisms associated with reduced psychological distress.
      Relatively little is known about the impact of RS on genomic health issues. The
      objectives of our study were: (1) describe the prevalence of RS and depressive
      symptoms and (2) explore how RS relates to psychological distress in a cohort of
      individuals with a > or =25% prior probability of a genetic predisposition to
      cancer. Participants (n = 99) were drawn from an African-American, Louisiana
      based kindred with a mutation at the BRCA1 locus. This analysis reports findings
      from a survey assessing RS and the use of three types of religious coping styles:
      collaborative, self-directing, and deferring. Clinically significant depressive
      symptoms were relatively high (27%); with females (33%) more likely than males
      (17%) to report symptoms (P < 0.01). The majority of participants reported being
      highly religious. The most commonly employed religious problem solving style used
      by participants was collaborative (X=22.9; SD=5.8) versus self-directing (X=12.8;
      SD = 5.1) and deferring (X=19.9; SD = 6.3). We did not observe significant
      associations between RS indicators and psychological distress, nor did we observe
      appreciable differences related to gender or risk perception. Although RS beliefs
      and practices are important for many African-Americans, we did not find evidence
      that indicators of self-reported RS are associated with psychological distress
      prior to genetic counseling and testing.

PMID- 19170080
TI  - Religion, spirituality, and genetics: mapping the terrain for research purposes.
AB  - Genetic diseases often raise issues of profound importance for human self
      understanding, such as one's identity, the family or community to which one
      belongs, and one's future or destiny. These deeper questions have commonly been
      seen as the purview of religion and spirituality. This essay explores how
      religion and spirituality are understood in the current US context and defined in
      the scholarly literature over the past 100 years. It is argued that a pragmatic,
      functional approach to religion and spirituality is important to understanding
      how patients respond to genetic diagnoses and participate in genetic therapies. A
      pragmatic, functional approach requires broadening the inquiry to include
      anything that provides a framework of transcendent meaning for the fundamental
      existential questions of human life. This approach also entails suspending
      questions about the truth claims of any particular religious/spiritual belief or
      practice. Three implications of adopting this broad working definition will be
      presented.

PMID- 19170081
TI  - Making sense of genetic uncertainty: the role of religion and spirituality.
AB  - This article argues that to the extent that religious and spiritual beliefs can
      help people cope with genetic uncertainty, a limited spiritual assessment may be
      appropriate in genetic counseling. The article opens by establishing why genetic
      information is inherently uncertain and why this uncertainty can be medically,
      morally, and spiritually problematic. This is followed by a review of the range
      of factors that can contribute to risk assessments, including a few heuristics
      commonly used in responses to uncertainty. The next two sections summarize recent
      research on the diverse roles of religious and spiritual beliefs in genetic
      decisions and challenges to conducting spiritual assessments in genetic
      counseling. Based on these findings, religious and spiritual beliefs are posited
      as serving essentially as a heuristic that some people will utilize in responding
      to their genetic risks. In the interests of helping such clients make informed
      decisions, a limited spiritual assessment is recommended and described. Some of
      the challenges and risks associated with this limited assessment are discussed.
      Since some religious and spiritual beliefs can conflict with the values of
      medicine, some decisions will remain problematic.

PMID- 19170082
TI  - Are enhancement technologies "unnatural"? Musings on recent Christian
      conversations.
AB  - Although distinctions between therapy and enhancement are difficult to draw with
      precision, especially in marginal cases, recent Christian discussions of
      enhancement technologies accept the general plausibility of distinctions drawn
      between therapeutic interventions and enhancement technologies by appealing to
      general understandings of nature and human nature. However, such appeals continue
      to be plagued by conceptual imprecision on several matters, including the status
      of nature as a source of moral insight, the scope of human responsibility in
      light of God's purposes, and the effects of sin and finitude on human freedom.

PMID- 19170083
TI  - The patient as person in an increasingly gene-centric universe: how healthcare
      professionals should think about genomics and evolution.
AB  - In the past, the primary threat to the patient as person was a medical
      utilitarianism that would sacrifice the individual for the collective, that would
      coercively (ab)use a person for the sake of an in-group's health or happiness.
      Today, the threat is not only from vainglorious social groups but also from
      valorized genes and genomes. An over-valuation of genes risks making persons seem
      epiphenomenal. A central thesis of this article is that religious healthcare
      professionals have unique resources to combat this.

PMID- 19170084
TI  - Christianity, health, and genetics.
AB  - Health is an intrinsic value that Christians should respect, but it is not the
      highest value. Christians should be willing to jeopardize their own health for
      the health of others, and should repudiate any idea that genetic problems are the
      result of sin. Rather, sin leads us to make genetic problems harder to live with
      than they should be.

PMID- 19170085
TI  - SHARPEN-systematic hierarchical algorithms for rotamers and proteins on an
      extended network.
AB  - Algorithms for discrete optimization of proteins play a central role in recent
      advances in protein structure prediction and design. We wish to improve the
      resources available for computational biologists to rapidly prototype such
      algorithms and to easily scale these algorithms to many processors. To that end,
      we describe the implementation and use of two new open source resources, citing
      potential benefits over existing software. We discuss CHOMP, a new object
      oriented library for macromolecular optimization, and SHARPEN, a framework for
      scaling CHOMP scripts to many computers. These tools allow users to develop new
      algorithms for a variety of applications including protein repacking, protein
      protein docking, loop rebuilding, or homology model remediation. Particular care
      was taken to allow modular energy function design; protein conformations may
      currently be scored using either the OPLSaa molecular mechanical energy function
      or an all-atom semiempirical energy function employed by Rosetta.

PMID- 19170086
TI  - Multilevel lateral extra-cavitary corpectomy and reconstruction for non
      contiguous metastatic lesions to the spine: case report and literature review.
AB  - In patients with metastatic disease to their spine and compromise of neurologic
      function, the challenge is to accomplish decompression of the neural elements and
      maintain mechanical stability but limit the risk and morbidity to the patient. In
      this case report the lateral extracavitary approach is employed to accomplish
      these tasks through a single approach in a patient with multiple non-contiguous
      sites of dorsal as well as ventral cord compression.

PMID- 19170087
TI  - Targeted lymph node evaluation in colorectal cancer: a decade of progress!

PMID- 19170088
TI  - Impact of depression on treatment effectiveness and gains maintenance in social
      phobia: a naturalistic study of cognitive behavior group therapy.
AB  - BACKGROUND: The impact of depression on cognitive behavioral group therapy (CBGT)
      for social phobia (SP) in a naturalistic outpatient setting was examined after
      treatment termination and at 1-year follow-up. METHODS: Consecutive SP
      outpatients (N=219) were diagnosed using a structured interview. CBGT was
      provided in 18 1.5-hr weekly sessions. At pretreatment and posttreatment
      questionnaires and clinician ratings were administered. Self-report measures were
      obtained at 1-year follow-up. The main outcome measure was the Liebowitz Social
      Anxiety Scale. RESULTS: CBGT was found to be effective in reducing both social
      anxiety (effect size=1.23) as well as depression (effect size=0.94). Individuals
      with generalized social phobia (GSP) and individuals with specific social phobia
      (SSP) differed in their presenting psychopathology and in their response to CBGT.
      Among treatment completers, 44% GSPs and 37% SSPs achieved at least 50%
      improvement, and 44% GSPs and 87% SSPs reported distress and functioning within
      the normal range at the end of treatment. Among SPs diagnosed with major
      depressive disorder (MDD) at the onset of treatment, SP symptoms aggravated
      during the follow-up period, whereas SPs not diagnosed with MDD experienced a
      further alleviation of SP symptoms during follow-up. CBGT provided in a public
      clinic to non-selected, mostly unmedicated and comorbid patients, is an effective
      treatment for the majority of SP sufferers. CONCLUSIONS: MDD at the onset of CBGT
      was not associated with poorer treatment response, but predicted exacerbation of
      SP symptoms following treatment termination. Depressed SPs may need additional
      intervention to maintain CBGT gains. SSPs may benefit from less intensive CBGT
      than GSPs.

PMID- 19170089
TI  - Social phobia in Finnish general adolescent population: prevalence, comorbidity,
      individual and family correlates, and service use.
AB  - BACKGROUND: Few studies have investigated the epidemiology of social phobia (SP)
      among early to middle adolescents, at the time of suggested mean onset of the
      disorder. The objective of this study was to investigate the prevalence,
      comorbidity, individual and familial correlates, and service use associated with
      SP among Finnish 12-17-year-old adolescents in general population. METHODS: A
      sample of 784 adolescents was screened with the Social Phobia Inventory, and a
      sub-sample (n=350) was interviewed with a semi-structured clinical interview to
      identify SP, sub-clinical SP (SSP), and a range of other axis I DSM-IV disorders.
      Individual and familial correlates, and service use associated with SP were also
      inquired. RESULTS: We found a 12-month prevalence of 3.2% for SP, and 4.6% for
      SSP. The prevalence rose and the gender ratio shifted to female preponderance as
      age increased. SP was frequently comorbid with other anxiety disorders (41%) and
      depressive disorders (41%). Adolescents with SP/SSP were impaired in their
      academic and global functioning, and reported more parental psychiatric treatment
      contacts. Two thirds (68%) of adolescents with SP reported having been bullied by
      peers. Only one fifth of adolescents with non-comorbid SP had been in contact
      with a mental health professional. CONCLUSIONS: We conclude that adolescent SP is
      a relatively frequent, undertreated and highly comorbid condition, associated
      with educational impairment, depression and anxiety in parents, and peer
      victimization.

PMID- 19170090
TI  - The personal is political, the professional is not: conscientious objection to
      obtaining/providing/acting on genetic information.
AB  - Conscientious objection (CO) to genetic testing raises serious questions about
      what it means to be a health-care professional (HCP). Most of the discussion
      about CO has focused on the logic of moral arguments for and against aspects of
      CO and has ignored the social context in which CO occurs. Invoking CO to deny
      services to patients violates both the professional's duty to respect the
      patient's autonomy and also the community standards that determine legitimate
      treatment options. The HCP exercising the right of CO may make it impossible for
      the patient to exercise constitutionally guaranteed rights to self-determination
      around reproduction. This creates a decision-making imbalance between the HCP and
      the patient that amounts to an abuse of professional power. To prevent such
      abuses, professionals who wish to refrain from participating have an obligation
      to warn prospective patients of their objections prior to establishing a
      professional-patient relationship or, if a relationship already exists, to
      arrange for alternative care expeditiously.

PMID- 19170091
TI  - God and genes in the caring professions: clinician and clergy perceptions of
      religion and genetics.
AB  - Little is known about how care providers' perceptions of religion and genetics
      affect interactions with patients/parishioners. This study investigates
      clinicians' and clergy's perceptions of and experiences with religion and
      genetics in their clinical and pastoral interactions. This is an exploratory
      qualitative study designed to elicit care providers' descriptions of experiences
      with religion and genetics in clinical or pastoral interactions. Thirteen focus
      groups were conducted with members of the caring professions: physicians, nurses,
      and genetics counselors (clinicians), ministers and chaplains (clergy).
      Preliminary analysis of qualitative data is presented here. Preliminary analysis
      highlights four positions in professional perceptions of the relationship between
      science and faith. Further, differences among professional perceptions appear to
      influence perceptions of needed or available resources for interactions with
      religion and genetics. Clinicians' and clergy's perceptions of how religion and
      genetics relate are not defined solely by professional affiliation. These non
      role-defined perceptions may affect clinical and pastoral interactions,
      especially regarding resources for patients and parishioners.

PMID- 19170092
TI  - Moving up the slippery slope: mandated genetic screening on Cyprus.
AB  - Many social scientists and bioethicists have argued that genetic screening is a
      new form of eugenics. Examination of the development of the quasi-mandated
      screening program for beta-thalassemia in the Republic of Cyprus (1970-1984)
      demonstrates that there is nothing eugenic about modern genetic screening
      practices. The Cypriot screening program involves mandated premarital carrier
      screening, voluntary prenatal diagnosis (originally through fetoscopy, now
      through CVS), and voluntary termination of afflicted pregnancies-all at public
      expense. In the Republic of Cyprus, the mandating agency for genetic screening is
      the established church, so this examination also demonstrates that religious
      authorities with profound objections to abortion can balance that moral precept
      against others, such as the imperative to reduce suffering that sometimes
      conflict with it.

PMID- 19170093
TI  - Religious traditions and prenatal genetic counseling.
AB  - Members of organized religious groups may look to their faith traditions for
      guidance regarding the moral implications of prenatal diagnosis and intervention.
      Many denominations have doctrinal statements relevant to these deliberations. In
      this article, common spiritual issues arising in the genetic counseling encounter
      are described. Representative doctrinal positions, derived from the responses of
      31 U.S. religious denominations to a survey relating to prenatal genetic
      counseling, are given. Because the long-term adjustment of patients may be
      dependent in part on their ability to reconcile their actions with their faith
      traditions, genetic counselors best serve their patients when they invite
      discussion of matters of faith. Unless invited, patients may assume these topics
      are "off limits" or that care providers are indifferent to their beliefs.
      Although genetics professionals ought not assume the role of spiritual advisor, a
      working knowledge of doctrinal approaches should help counselors frame the
      issues, and avoid missteps.

PMID- 19170094
TI  - Periodic knee injections of BMP-7 delay cartilage degeneration induced by
      excessive running in rats.
AB  - Strenuous running of rats enhances mechanical stress on the knee, thereby
      inducing degeneration of articular cartilage. Bone morphogenetic protein-7 (BMP
      7) has an inhibitory effect on cartilage degeneration, suggesting its usefulness
      for human osteoarthritis patients. However, its mode of administration should be
      investigated. We examined whether weekly knee injections of BMP-7 delayed the
      progression of cartilage degeneration. Wistar rats were forced to run 30 km in 6
      weeks on a rodent treadmill, and BMP-7 was injected weekly into the knee.
      Macroscopically and histologically, this strenuous running regimen induced
      cartilage degeneration. Weekly injections of 250 ng BMP-7 delayed the progression
      of cartilage degeneration. Immunohistochemically, in the control knee, type II
      collagen expression decreased, while BMP-7 expression in chondrocytes slightly
      increased. Interestingly, weekly injection of BMP-7 increased BMP-7 expression
      even 9 days after the final injection. Disulfate disaccharide keratan sulfate in
      serum transiently increased in the control group, while it remained at a low
      level in the BMP-7 group. Weekly BMP-7 injection increased BMP-7 expression in
      chondrocytes and its effect seemed to last more than 7 days. The effect of BMP-7
      could be monitored by serum keratan sulfate concentration. Periodical injections
      of BMP-7 delayed progression of cartilage degeneration induced by excessive
      running in rats.

PMID- 19170095
TI  - Fat marrow embolism during intramedullary bone endoscopy: an experimental study
      in sheep.
AB  - We present a study designed to investigate whether the intramedullary bone
      endoscopy (IBE) procedure within the cavity of an intact long bone will create
      embolic loads on the lungs similar to that of other orthopedic procedures (e.g.,
      stem implantation in total hip arthroplasty [THA]). In a sheep model, 10 animals
      underwent the IBE procedure with complete perioperative anesthesiology
      monitoring. The lungs were harvested postoperatively and examined for fat
      embolisms. One animal showed evidence of intraoperative fat embolism with
      temporary increases in mean pulmonary arterial pressure (MPAD) and the mean CO(2)
      gradient. The histological examination in this animal revealed fat embolism with
      a 2% surface area of the investigated fields covered with fat vacuoles. All peri-
      and postoperative data on the other nine animals were normal. Our findings
      indicate that, as with other intramedullary manipulation in intact long bones,
      there is a potential risk for systemic fat excavation during IBE. However, the
      embolic load is much lower than the rates reported for other orthopedic
      interventions.

PMID- 19170096
TI  - Recombinant human platelet-derived growth factor BB (rhPDGF-BB) and beta
      tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat
      model.
AB  - Diabetes mellitus is a common systemic disease that has been associated with poor
      fracture healing outcomes. The mechanism through which diabetes impairs bone
      regeneration is unknown. One possible mechanism may be related to either
      decreased or uncoordinated release of local growth factors at the fracture site.
      Indeed, previous studies have found reduced platelet-derived growth factor (PDGF)
      levels in the fracture callus of diabetic rats, suggesting that local application
      of PDGF may overcome the negative effects of diabetes and promote fracture
      healing. To test this hypothesis, low (22 microg) and high (75 ug) doses of
      recombinant human PDGF-BB (rhPDGF-BB) were applied directly to femur fracture
      sites in BB Wistar diabetic rats that were then compared to untreated or vehicle
      treated animals. rhPDGF-BB treatment significantly increased early callus cell
      proliferation compared to that in control specimens. Low dose rhPDGF-BB treatment
      significantly increased callus peak torque values (p < 0.05) at 8 weeks after
      fracture as compared to controls. High dose rhPDGF-BB treatment increased callus
      bone area at 12 weeks postfracture. These data indicate that rhPDGF-BB treatment
      ameliorates the effects of diabetes on fracture healing by promoting early
      cellular proliferation that ultimately leads to more bone formation. Local
      application of rhPDGF-BB may be a new therapeutic approach to treat diabetes
      impaired fracture healing.

PMID- 19170097
TI  - Temporal growth factor release from platelet-rich plasma, trehalose lyophilized
      platelets, and bone marrow aspirate and their effect on tendon and ligament gene
      expression.
AB  - Platelet-rich plasma (PRP) has generated substantial interest for tendon and
      ligament regeneration because of the high concentrations of growth factors in
      platelet alpha-granules. This study compared the temporal release of growth
      factors from bone marrow aspirate (BMA), PRP, and lyophilized platelet product
      (PP), and measured their effects on tendon and ligament gene expression. Blood
      and BMA were collected and processed to yield PRP and plasma. Flexor digitorum
      superficialis tendon (FDS) and suspensory ligament (SL) explants were cultured in
      10% plasma in DMEM (control), BMA, PRP, or PP. TGF-beta1 and PDGF-BB
      concentrations were determined at 0, 24, and 96 h of culture using ELISA.
      Quantitative RT-PCR for collagen types I and III (COL1A1, COL3A1), cartilage
      oligomeric matrix protein (COMP), decorin, and matrix metalloproteinases-3 and 13
      (MMP-3, MMP-13) was performed. TGF-beta1 and PDGF-BB concentrations were highest
      in PRP and PP. Growth factor quantity was unchanged in BMA, increased in PRP, and
      decreased in PP over 4 days. TGF-beta1 and platelet concentrations were
      positively correlated. Lyophilized PP and PRP resulted in increased COL1A1:COL3A1
      ratio, increased COMP, and decreased MMP-13 expression. BMA resulted in decreased
      COMP and increased MMP-3 and MMP-13 gene expression. Platelet concentration was
      positively correlated with COL1A1, ratio of COL1A1:COL3A1, and COMP, and
      negatively correlated with COL3A1, MMP-13, and MMP-3. White blood cell
      concentration was positively correlated with COL3A1, MMP3, and MMP13, and
      negatively correlated with a ratio of COL1A1:COL3A1, COMP, and decorin. These
      findings support further in vivo investigation of PRP and PP for treatment of
      tendonitis and desmitis.

PMID- 19170098
TI  - Religious and spiritual issues in medical genetics.
AB  - This article provides an overview of a special issue on the religious and
      spiritual concerns that arise in the provision of genetic services. It introduces
      some of the challenges in defining religion and spirituality and provides
      contexts and summaries for the empirical and normative research that appears in
      the issue.

PMID- 19170099
TI  - A religious framework as a lens for understanding the intersection of genetics,
      health, and disease.
AB  - The primary goal of this study was to determine the extent to which religious
      frameworks inform lay public understandings of genes and disease. Contrary to
      existing research, there were minimal differences between racial groups. We did,
      however, observe two patterns in that data that are worthy of discussion. First,
      because participants were from the south, the finding that participants from both
      racial groups ascribe to a religious belief system to make sense of their lived
      experiences is not surprising. Rather, it appears to be reflective of the
      religious culture that is an integral part of the south and our identity as a
      nation. A second noteworthy finding is that while a significant number of
      participants believe that a relationship exists between health status, genes, and
      religious behaviors, they also recognize that positive health behaviors must also
      be adopted as a means for staving off disease. In some cases, however, there was
      a belief that health issues could dissolve or disappear as a result of certain
      religious behaviors such as prayer.

PMID- 19170100
TI  - The role and impact of personal faith and religion among genetic service
      providers.
AB  - This paper describes the impact of genetic service providers' personal faith and
      religious values on their experiences interacting with colleagues and patients.
      We surveyed 480 clinical geneticists (MDs), genetic counselors (GCs), and genetic
      nurses randomly selected from their professional associations, and then
      interviewed a sample of survey respondents. Outcomes included religiosity, coping
      with distress through spiritual beliefs, and personal value conflicts (PVCs). Two
      hundred fourteen providers completed the survey out of an estimated 348 eligible
      (61% response rate). Importance attributed to regular attendance at religious
      services ranged from 39% (not at all important) to 27% (very important). Reliance
      on religion and spiritual beliefs as a source of comfort ranged from 48% (never)
      to 33% (sometimes or often). Religiosity varied by discipline with 58% of nurses
      thinking regular attendance at religious services was moderately or very
      important as compared to 47% of GCs and 30% of MDs (P = 0.006). Ten percent of
      respondents had difficulty reconciling their own faith with being a genetics
      professional, 14% felt the need to hide their own faith from their colleagues or
      patients, 7% thought their professional stance was not consistent with their
      personal values, and 4% felt ostracized by the genetics community because of
      their personal beliefs. The experience of such PVCs was positively correlated
      with religiosity (r = 0.35; P < 0.0001). GCs were more likely to experience PVCs
      than MDs or nurses (P = 0.013). Data from the interviews (N = 54) support these
      findings. A significant minority of genetic service providers are religiously
      observant and rely on their religious values to cope with distress. These
      individuals often experience difficulty reconciling their religious beliefs with
      the expectations of their profession, and sharing their beliefs with their
      colleagues and patients. Efforts should be made to prevent or reduce the secrecy
      surrounding personal faith and religion among genetics professionals.

PMID- 19170101
TI  - Risk factors for relapse after remission with repetitive transcranial magnetic
      stimulation for the treatment of depression.
AB  - BACKGROUND: Several studies have shown that repetitive transcranial magnetic
      stimulation (rTMS) treatment is associated with a significant antidepressant
      effect that can last for several months. METHODS: To investigate the mean
      remission time and the predictors associated with its duration; we performed a
      large retrospective, naturalistic study with 204 patients who underwent treatment
      with rTMS. During the periods from 2000 to 2006, we identified and collected the
      data on 204 patients who underwent rTMS treatment for major depression and who
      remitted their depression (defined as Hamilton Depression Rating Scores less or
      equal to 7). Patients were followed up to 6 months after this therapy. RESULTS:
      Event-free remission with the end point defined as relapse (Hamilton Depression
      Rating Scores higher than 8) was 75.3% (73.7) at 2 months, 60.0% (74.5) at 3
      months, 42.7% (74.8) at 4 months, and 22.6% (74.5) at 6 months. According to a
      multivariate analysis, only the age and number of sessions were independent
      predictors of outcome. Although depression severity and use of tricyclics also
      showed a significant relationship with remission duration, the model including
      these variables was not adequate to explain our data. CONCLUSIONS: The results of
      this study suggest that young age and additional rTMS sessions are associated
      with a ong duration of rTMS effects and therefore future trials investigating the
      effects of maintenance rTMS treatment need to explore further the implication of
      these factors for depression remission.

PMID- 19170102
TI  - Human tonic immobility: measurement and correlates.
AB  - BACKGROUND: Tonic immobility (TI) is a temporary state of motor inhibition
      believed to be a response to situations involving extreme fear. Limited attention
      has been directed to studying TI in humans; however, the phenomenon has been well
      documented in the animal literature. In humans, TI is believed to occur during
      sexual assault, and there have been reports of fear-induced freezing in the
      contexts of air, naval, and other disasters. METHODS: This study had three main
      purposes: (1) to assess the factor structure of a new self-report measure--the
      Tonic Immobility Questionnaire--designed to assess human TI in a range of
      traumatic events; (2) to explore associations among discovered TIQ factors and a
      measure of posttraumatic symptoms in the context of trauma type; and (3) to
      determine whether TI is related to suspected and empirically supported predictors
      of posttraumatic stress disorder. Participants were a subset of undergraduate
      students (n=78) who reported a TI experience in the context of a traumatic event.
      RESULTS: No differences were found in frequency or severity of TI reported across
      trauma types. Exploratory factor analysis of Tonic Immobility Questionnaire item
      responses resulted in a three-factor solution (i.e., physical immobility, fear,
      and dissociation). Significant positive correlations were found between the Tonic
      Immobility Questionnaire and measures of posttraumatic symptoms, dissociation,
      anxiety sensitivity, and absorption. Regression analysis revealed that
      peritraumatic dissociation scores alone accounted for 51% of the variance in TI
      scores. CONCLUSIONS: TI may represent an extreme behavioral expression of trauma
      induced peritraumatic dissociation. Implications and directions for future
      research are discussed.

PMID- 19170103
TI  - Throughout Today's Industrial societies, huge numbers of children and adolescents
      suffer from mental health problems.

PMID- 19170104
TI  - "Life grows between the rocks": Latino adolescents' and parents' perspectives on
      mental health stressors.
AB  - Latino adolescents, an increasingly larger proportion of youth in the US, are at
      special risk for mental health problems, including depression and suicidal
      ideation. Little is known about the meaning of mental health stressors for Latino
      adolescents and their parents. We conducted a descriptive study to elicit Latino
      adolescents' and parents' perspectives regarding mental health stressors as a
      basis for future preventive interventions. Eight focus groups were conducted with
      53 Latino participants, 2 per sub-group (boys, girls, mothers, fathers). Three
      categories of mental health stressors included discrimination, immigration, and
      familial disconnection. Findings support the need for collaborative interventions
      and multi-level strategies (individual, family, and community) to address
      stressors in Latino adolescents' experiences.

PMID- 19170106
TI  - Correlates and mediators of functional disability in obsessive-compulsive
      disorder.
AB  - BACKGROUND: This study examined factors associated with obsessive-compulsive
      disorder (OCD) related functional disability in 87 treatment-seeking adults with
      OCD. METHODS: A trained evaluator administered the Yale-Brown Obsessive
      Compulsive Scale and Brown Assessment of Beliefs Scale. Patients completed the
      Sheehan Disability Scale, Obsessive-Compulsive Inventory-Revised, Interpretation
      of Intrusions Inventory, Thought-Action Fusion Scale, Beck Depression Inventory
      Second Edition, and State Trait Anxiety Inventory-Trait Version. RESULTS: Results
      indicated that OCD symptoms, anxiety, depression, and the tendency to
      misinterpret the significance of intrusive thoughts were related to functional
      disability. Two variables-depressive symptoms and the extent to which a patient
      attempts to resist and is able to control OCD symptoms-emerged as unique
      predictors of functional disability. Mediational analyses indicated that both of
      these variables fully mediated the relationship between OCD-related distress and
      functional disability. CONCLUSIONS: Results are discussed in terms of predictors
      of functional disability in OCD and in terms of implications for assessment and
      treatment.

PMID- 19170105
TI  - CDK inhibitors selectively diminish cell cycle controlled activation of the
      histone H4 gene promoter by p220NPAT and HiNF-P.
AB  - Cell cycle progression into S phase requires the induction of histone gene
      expression to package newly synthesized DNA as chromatin. Cyclin E stimulation of
      CDK2 at the Restriction point late in G1 controls both histone gene expression by
      the p220(NPAT)/HiNF-P pathway and initiation of DNA replication through the
      pRB/E2F pathway. The three CDK inhibitors (CKIs) p21(CIP1/WAF1), p27(KIP1), and
      p57(KIP2) attenuate CDK2 activity. Here we find that gamma-irradiation induces
      p21(CIP1/WAF1) but not the other two CKIs, while reducing histone H4 mRNA levels
      but not histone H4 gene promoter activation by the p220(NPAT)/HiNF-P complex. We
      also show that p21(CIP1/WAF1) is less effective than p27(KIP1) and p57(KIP2) in
      inhibiting the CDK2 dependent phosphorylation of p220(NPAT) at subnuclear foci
      and transcriptional activation of histone H4 genes. The greater effectiveness of
      p57(KIP2) in blocking the p220(NPAT)/HiNF-P pathway is attributable in part to
      its ability to form a specific complex with p220(NPAT) that may suppress
      CDK2/cyclin E phosphorylation through direct substrate inhibition. We conclude
      that CKIs selectively control stimulation of the histone H4 gene promoter by the
      p220(NPAT)/HiNF-P complex.

PMID- 19170107
TI  - Sonographic measurement of cross-sectional area of the median nerve in the
      diagnosis of carpal tunnel syndrome: correlation with nerve conduction studies.
AB  - PURPOSE: To assess the usefulness of sonographic measurement of the median nerve
      cross-sectional area (CSA) in the diagnosis of carpal tunnel syndrome (CTS) and
      grading of its severity using nerve conduction (NC) studies as the standard.
      METHOD: The CSA of the median nerve was measured at the tunnel inlet and outlet
      using the ellipse formula and automatic tracing in 72 hands with suspicion of
      CTS. RESULT: The lack of inter-reader reliability led to excluding CSA
      measurements obtained at the tunnel outlet. Based on the receiver operating
      characteristic curves, the following cut-off points for the CSA of the median
      nerve at the tunnel inlet was selected: 9.8 mm and 12.3 mm(2) for the ellipse
      formula and 11 and 13 mm(2) for automatic tracing. For the ellipse formula, a CSA
      less than or equal to 9.8 mm(2) excluded CTS whereas a CSA greater than or equal
      to 12.3 mm(2) was diagnostic of CTS with measurements between 9.8 and 12.3 mm(2)
      being indeterminate and requiring NC studies. For automatic tracing, the cutoff
      value of 11 mm(2) was excluded because of the high percentage of false negatives,
      whereas CSAs greater than or equal to 13 mm(2) were diagnostic of CTS. There were
      no statistically significant differences in CSA measurements between the various
      degrees of CTS severity determined by NC studies. CONCLUSION: Sonographic
      measurement of median nerve CSA at the tunnel inlet is a good alternative to NC
      studies as the initial diagnostic test for CTS, but it cannot grade the severity
      of CTS as well as NC studies.

PMID- 19170108
TI  - Mitochondrial localization, ELK-1 transcriptional regulation and growth
      inhibitory functions of BRCA1, BRCA1a, and BRCA1b proteins.
AB  - BRCA1 is a tumor suppressor gene that is mutated in families with breast and
      ovarian cancer. Several BRCA1 splice variants are found in different tissues, but
      their subcellular localization and functions are poorly understood at the moment.
      We previously described BRCA1 splice variant BRCA1a to induce apoptosis and
      function as a tumor suppressor of triple negative breast, ovarian and prostate
      cancers. In this study we have analyzed the function of BRCA1 isoforms (BRCA1a
      and BRCA1b) and compared them to the wild-type BRCA1 protein using several
      criteria like studying expression in normal and tumor cells by RNase protection
      assays, subcellular localization/fractionation by immunofluorescence microscopy
      and Western blot analysis, transcription regulation of biological relevant
      proteins and growth suppression in breast cancer cells. We are demonstrating for
      the first time that ectopically expressed GFP-tagged BRCA1, BRCA1a, and BRCA1b
      proteins are localized to the mitochondria, repress ELK-1 transcriptional
      activity and possess antiproliferative activity on breast cancer cells. These
      results suggest that the exon 9, 10, and 11 sequences (aa 263-1365) which contain
      two nuclear localization signals, p53, Rb, c-Myc, gamma-tubulin, Stat, Rad51,
      Rad50 binding domains, angiopoietin-1 repression domain are not absolutely
      required for mitochondrial localization and growth suppressor function of these
      proteins. Since mitochondrial dysfunction is a hallmark of cancer, we can
      speculate that the mitochondrial localization of BRCA1 proteins may be
      functionally significant in regulating both the mitochondrial DNA damage as well
      as apoptotic activity of BRCA1 proteins and mislocalization causes cancer. J.
      Cell. Physiol. 219: 634-641, 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19170109
TI  - Msx2 induces epithelial-mesenchymal transition in mouse mammary epithelial cells
      through upregulation of Cripto-1.
AB  - Epithelial-mesenchymal transition (EMT) is a process occurring during both
      embryogenesis and early stages of invasive cancer. Epithelial cells that undergo
      EMT become more migratory and invasive with a mesenchymal morphology. Herein we
      assess EMT induction in a mouse mammary epithelial cell line driven by Msx2, a
      homeobox-containing transcription factor important during mammary gland
      development. NMuMG cells, a normal mouse mammary epithelial cell line, stably
      transfected with a Msx2 cDNA showed downregulation of an epithelial marker E
      cadherin and upregulation of the mesenchymal markers vimentin and N-cadherin.
      Furthermore, overexpression of Cripto-1, a member of the epidermal growth factor
      CFC protein family already known to be involved in EMT, was detected in Msx2
      transfected cells. The expression of Cripto-1 was accompanied by activation of
      the tyrosine kinase c-Src pathway and an increase in the invasive ability of the
      cells. Functional assays also demonstrated inhibition of the invasive behavior of
      the Msx2-transfected cells by a c-Src specific inhibitor. Moreover,
      immunohistochemistry of human infiltrating breast carcinomas showed positive
      staining for Msx2 only in the infiltrating tumor cells while the non-infiltrating
      tumor cells were negative. These results suggest that Msx2 may play a significant
      role in promoting EMT in epithelial cells that acquire properties involved in
      tumor invasion. J. Cell. Physiol. 219: 659-666, 2009. Published 2009 Wiley-Liss,
      Inc.

PMID- 19170110
TI  - Myelotoxicity of preoperative chemoradiotherapy is a significant determinant of
      poor prognosis in patients with T4 esophageal cancer.
AB  - PURPOSE: Currently, preoperative chemoradiotherapy followed by surgery is the
      only promising strategy for patients with T4 esophageal cancer. This study
      retrospectively analyzed the prognostic factors in patients with curatively
      resected cancer after chemoradiotherapy. PATIENTS AND METHODS: Between September
      1989 and December 2003, 42 patients with T4 esophageal cancer received
      preoperative chemoradiotherapy (CRT) followed by curative surgery. Chemotherapy
      consisted of 5-fluorouracil/cisplatin (FP) or 5-fluorouracil/adriamycin/cisplatin
      (FAP). A total dose of 40 Gy of radiation was delivered concurrently. Surgery was
      scheduled 4 weeks after the completion of CRT. The treatment response was
      categorized using general criteria. Toxicities of the CRT were assessed according
      to National Cancer Institute of Common Toxicity Criteria (NCI-CTC). Univariate
      and multivariate analyses were performed to identify significant prognostic
      clinicopathological factors. RESULTS: The overall survival rate was 38.4% at 5
      years. The toxic grade for leukopenia (grade 0-2/3-4) and pathological effect
      (grade 3/1-2) were significantly different by univariate analysis (P = 0.03 and
      0.05, respectively). Multivariate analysis identified the toxic grade for
      leukopenia as the only significant and independent determinant of prognosis (P =
      0.05). CONCLUSION: In patients with T4 esophageal cancer who receive CRT followed
      by curatively resection, myelogenic chemotoxicity is a significant prognostic
      factor.

PMID- 19170112
TI  - The hidden crisis in mental health and education: the gap between student needs
      and existing supports.
AB  - The authors provide a selected review of mental health and educational concerns
      evident in U.S. middle schools and describes promising and important strategies
      to ameliorate the high rates of students with mental health and academic
      difficulties. Despite some promising and important strategies, service systems
      are fragmented, and comprehensive systems of supports are still in development.
      Furthermore, there remains a lack of integrated developmental considerations in
      practice. The RALLY approach systematically introduces development and caring
      adult relationships into preventive practice and combines mental health,
      education, and youth development to promote students' resiliency and academic
      potential.

PMID- 19170113
TI  - Responding to the crisis: RALLY's developmental and relational approach.
AB  - The authors introduce the RALLY (Responsive Advocacy for Life and Learning in
      Youth) approach. RALLY is a school- and after school-based approach addressing
      academic success, youth development, and mental health for youth. Based on
      developmental and relational principles, RALLY's main goals are to promote
      students' resiliency, development, and academic functioning, as well as to reduce
      the typical adolescent's risks. By implementing a new professional role of RALLY
      practitioners, who are developmental specialists and interconnect the different
      social worlds of students, RALLY creates the resources to provide social
      opportunities and quality practices to meet students' needs and facilitate their
      growth. A three-tiered system helps to implement mental health and educational
      practice, thus providing differential support for students with different needs.
      Early identification of risks and resiliencies helps to avoid chronicity and
      pinpoint adequate treatments as soon as possible.

PMID- 19170114
TI  - A new developmentalist role: connecting youth development, mental health, and
      education.
AB  - The RALLY practitioner implements RALLY's prevention and intervention strategies,
      working with all of the students in a class to deliver nonstigmatizing,
      developmentally based services. The practitioner model is based on the philosophy
      that relationships are key to allowing students to achieve their full health and
      academic potential. RALLY practitioners work within the classroom individually,
      in small groups, and in after-school time. In all of these contexts, RALLY
      practitioners focus on four major functions: (1) building strong relationships
      with students, (2) providing developmental and academic support, (3) referring
      students to services based on their needs and interests, and (4) connecting with
      teachers, families, clinicians, after-school staff, and other service providers
      in order to bridge these worlds. RALLY practitioners offer an in-novative model
      to bring mental health and educational support into schools. They have varying
      educational backgrounds, from high school graduates, to college students, to
      graduate interns in mental health or education professions. Training and
      supervision, however, are crucial in helping practitioners of all levels to
      create integrated systems of support that take all of a student's interests and
      needs into consideration while moving toward academic success.

PMID- 19170115
TI  - Reinventing clinical roles and space at school.
AB  - Recognizing both the need for youth-focused acute mental health services and the
      barriers for low-income families to access outside services, the RALLY Program
      expanded its services to include direct clinical services for students within the
      school setting. This article explores the challenges, strategies, and benefits of
      implementing a fluid range of formal and informal clinical interventions within
      RALLY's nonstigmatizing, developmental, and inclusive approach. Balancing
      insurance company demands with students' nonbillable needs requires diverse
      funding streams and responsive programming. Creative use of space, commitment to
      relationships, and flexibility of roles form the foundation of this approach.
      Through case studies, the author examines practical and creative applications of
      developmental theories adaptable to individual students' unique needs. The author
      concludes with recommendations to the field to strengthen nonstigmatizing
      services offered to address the holistic needs of youth at school.

PMID- 19170116
TI  - Creating youth leaders: community supports.
AB  - In order to maximize the effectiveness of prevention and intervention efforts
      with youth and address the needs of the whole student, it is necessary to work
      not only directly with youth, but also to partner with other key adults in a
      young person's life: parents and guardians, teachers, after-school staff, and
      clinicians. Inherent in RALLY's philosophy is a dual strategy of working
      intensively with students and teachers in the school while creating partnerships
      that bring students' families and a network of community agencies into the school
      as well. These partnerships bring important resources to school communities and
      create richer opportunities for young people and their families. Furthermore, a
      key to working effectively with youth lies in providing them not only with
      services that match their needs and interests, but also opportunities for
      participation and empowerment. Such opportunities can result in significant
      individual change in the students involved in these opportunities as well as
      broader community.

PMID- 19170117
TI  - Holistic student assessments.
AB  - An assessment from a holistic perspective considers the overall well-being of the
      adolescent and seeks to understand the adolescent's development and resiliency in
      relation to social relationships and their context and risks, given the
      association between these factors and the goal to promote each area. It is
      recommended that measures in the assessment obtain information from each of these
      factors from paper-and-pencil questionnaires, to more qualitative means such as
      forging relationship with practitioners. Ideally, an assessment should be easily
      administered by youth workers such as practitioners. A successful assessment
      procedure includes translation of the assessment findings to a referral by the
      assessment administrator to explain why the service is needed.

PMID- 19170118
TI  - Program evaluation: relationships as key to student development.
AB  - Evaluation is an important program component of RALLY and helps to document the
      gains that stem from this program. This article describes the quality of RALLY
      implementation and selected student outcomes of an exemplary RALLY program at an
      urban middle school. The findings showed effects on students' resiliency as well
      as academic success, as indicated by student, practitioner, and teacher reports.
      The practitioners and teachers also reported a decrease in students' behavioral
      problems. Relationships to practitioners and a developmental orientation proved
      to be of key significance for changes in students' resiliency and academic
      outcomes.

PMID- 19170119
TI  - Future systemic transformations.
AB  - This final article addresses the need to create further evidence that the
      integration of student support and after-school programming enhances student
      learning and thriving inside and outside schools. Many models are being put
      forward to address student support, but research findings on their effectiveness
      have been surprisingly mixed and designs have often been flawed. When
      interventions are tied to classrooms and support students, teachers, and
      administrators, an increase in effectiveness can be expected as compared to a
      wrap-around model that leaves the classroom and much of the school day as the
      sole domain of teachers. The authors describe the next steps for the RALLY
      approach, especially the creation of a train-the-trainer model for school
      districts, after-school programs, and mental health agencies.

PMID- 19170120
TI  - Approach-avoidance coping conflict in a sample of burn patients at risk for
      posttraumatic stress disorder.
AB  - BACKGROUND: Following an acute burn injury, higher distress is consistently
      observed among individuals exhibiting a conflict between approach coping (e.g.,
      processing) and avoidance coping (e.g., suppression) relative to those
      individuals who use only one of these methods. Study objectives were to determine
      if contradictory coping messages would lead to such approach-avoidance coping
      conflict and to determine if experiment-induced coping conflict is also
      associated with higher distress. METHODS: Participants (n=59 adults hospitalized
      with acute burn injuries) were assigned randomly to experimental conditions
      differing in the order in which training was provided in two ways of coping with
      posttrauma re-experiencing symptoms (i.e., process-then-suppress versus suppress
      then-process). The primary dependent variable was coping behavior during the 24
      hr posttraining period. Coping behavior was categorized as approach coping
      (processing), avoidance coping (suppressing), or approach-avoidance coping
      conflict (both) on the basis of median splits on subscales assessing these
      behaviors. Secondary analyses examined the relationship between this experiment
      induced coping conflict and re-experiencing symptoms. RESULTS: Results indicated
      that participants in the process-then-suppress condition, relative to the
      suppress-then-process condition, were significantly more likely to exhibit
      approach-avoidance coping conflict (i.e., above median split on both processing
      and suppressing) during the next 24 hr. Furthermore, approach-avoidance coping
      conflict was associated with greater re-experiencing symptoms assessed via self
      report and by blinded coding of recorded speech. CONCLUSIONS: It is concluded
      that the order of coping skill training can influence treatment outcome, success
      of coping methods, and overall levels of distress. therefore, training in
      stabilizing and calming methods should precede training in active processing
      following stressful life events.

PMID- 19170121
TI  - Decreased expression and promoter methylation of the menin tumor suppressor in
      pancreatic ductal adenocarcinoma.
AB  - Loss of menin, a tumor suppressor coded by the MEN1 gene, is a key factor in the
      pathogenesis of multiple endocrine neoplasia type I and in a percentage of
      sporadic endocrine tumors of the pancreas and parathyroid glands. This study
      investigated expression of the menin protein in the normal exocrine pancreas and
      in pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic tumor.
      Immunofluorescence (IF) analyses showed that menin is expressed at high levels in
      normal acinar and duct cells. Examination of 24 clinical samples of PDAC revealed
      a pronounced decrease in menin expression in all tumors examined. To identify
      alterations underlying this defect, we searched for disruption and epigenetic
      silencing of the MEN1 gene. Analysis of nine laser-microdissected tumors revealed
      loss of heterozygosity of intragenic (one tumor) or adjacent (three tumors) MEN1
      microsatellite markers. Methylation of CpG sites in the MEN1 promoter was
      documented in five of 24 tumors. IF analyses also revealed low to undetectable
      menin expression in the PDAC cell lines MiaPaCa-2 and Panc-1. Ectopic expression
      of menin in these cells resulted in a marked alteration of the cell cycle, with
      an increase in the G1/S+G2 ratio. These findings represent the first evidence
      that the MEN1 gene is a target of mutation and methylation in PDAC and that menin
      influences the cell cycle profile of duct cells.

PMID- 19170122
TI  - Sonographic surface localization of subcutaneous foreign bodies and masses.
AB  - We report a sonographic technique of skin marking of the projection of
      nonpalpable subcutaneous foreign bodies and masses using a paperclip.
      Localization and marking of the overlying skin assists in preoperative planning
      and further management.

PMID- 19170123
TI  - Sclerosing angiomatoid nodular transformation (SANT) of the spleen: sonographic
      finding.
AB  - Sclerosing angiomatoid nodular transformation (SANT) is a recently recognized
      benign vascular lesion of the spleen. There is limited information regarding its
      imaging findings of this condition. Until now, the diagnosis was based on
      histopathologic examination of splenectomy specimens. We report the sonographic
      findings in a case of SANT of the spleen confirmed by ultrasound-guided core
      needle biopsy.

PMID- 19170124
TI  - A worldwide approach to the TNM staging system: collaborative efforts of the AJCC
      and UICC.

PMID- 19170125
TI  - Thyroid hormone treatment of cultured chondrocytes mimics in vivo stimulation of
      collagen X mRNA by increasing BMP 4 expression.
AB  - During endochondral bone formation, chondrocytes undergo terminal
      differentiation, during which the rate of proliferation decreases, cells become
      hypertrophic, and the extracellular matrix is altered by production of collagen
      X, as well as proteins required for matrix mineralization. This maturation
      process is responsible for most longitudinal bone growth, both during embryonic
      development and in postnatal long bone growth plates. Among the major signaling
      molecules implicated in regulation of this process are the positive regulators
      thyroid hormone (T3) and bone morphogenetic proteins (BMPs). Both T3 and BMPs are
      essential for endochondral bone formation and cannot compensate for each other,
      suggesting interaction of the two signaling pathways. We have analyzed the
      temporal and spatial expression patterns of numerous genes believed to play a
      role in chondrocyte maturation. Our results show that T3 stimulates collagen X
      gene expression in cultured chondrocytres with kinetics and magnitude similar to
      those observed in vivo. Stimulation of collagen X gene expression by T3 occurs
      only after a significant delay, implying that this hormone may act indirectly. We
      show further that T3 rapidly stimulates production of BMP 4, concomitant with a
      decrease in the BMP inhibitor Noggin, potentially resulting in a net increase in
      BMP signaling. Finally, inhibition of BMP signaling with exogenous Noggin
      prevents T3 stimulation of collagen X expression, indicating that BMP signaling
      is essential for this process. These data position thyroid hormone at the top of
      a T3/BMP cascade, potentially explaining why both pathways are essential for
      chondrocyte maturation. J. Cell. Physiol. 219: 595-605, 2009. (c) 2009 Wiley
      Liss, Inc.

PMID- 19170126
TI  - Over-expression of IkappaB-kinase-epsilon (IKKepsilon/IKKi) induces secretion of
      inflammatory cytokines in prostate cancer cell lines.
AB  - BACKGROUND: Elevated inflammatory cytokine levels in serum have been associated
      with advanced stage metastasis-related morbidity in prostate cancer. Several
      studies have shown that IL-6 and IL-8 can accelerate the growth of human prostate
      cancer cell lines. Previous studies, in murine embryonic fibroblasts, have shown
      that Ikappa-B kinase-epsilon (IKKepsilon/IKKi)-deficiency results in the
      reduction of lipopolysaccharide-mediated expression of IL-6. RESULTS: In this
      study, we report that over-expression of IKKepsilon in hormone-sensitive 22Rv1
      and LNCaP prostate cancer cells induces the secretion of several inflammatory
      cytokines including IL-6 and IL-8. Both of these cytokines are secreted by
      hormone-refractory PC-3 prostate cancer cells and IKKepsilon knock-down in these
      cells correlates with a strong decrease in IL-6 secretion. Furthermore, we
      demonstrate that IKKepsilon over-expression does not induce the activation of the
      IKKepsilon classical targets NF-kappaB and IRF-3, two transcription factors
      involved in the regulation of several cytokines. Finally, we observe that high
      IKKepsilon expression results in its nuclear translocation, a phenomena that is
      TBK1-independent. CONCLUSIONS: This study identifies IKKepsilon as a potential
      prostate cancer gene that may favor chronic inflammation and create a tumor
      supporting microenvironment that promotes prostate cancer progression,
      particularly by the induction of IL-6 secretion that may act as a positive growth
      factor in prostate cancer.

PMID- 19170128
TI  - Conception of a navigation system controlling diaphyseal fracture reduction
      treated with external fixation.
AB  - BACKGROUND: The reduction of long bone fractures treated with external fixation
      is usually performed with fluoroscopic images, which include several
      disadvantages: 2D information, distortions, and irradiation to the patient and
      the surgical team. This article presents a new navigation technique to control
      the reduction of such fractures while minimizing the irradiation. METHODS:
      Optically tracked markers are fixed to pins inserted into the bone fragments.
      These last are modelled using two initial calibrated radiographs. The models can
      be improved with several types of anatomical data and are displayed in real time.
      RESULTS: This navigation system was tested on dry bones and an anatomical
      specimen leg. CONCLUSIONS: This new technique allows the visualization of the
      fracture in real time and from any viewpoint during the reduction. Irradiation is
      minimized using only two X-ray images.

PMID- 19170127
TI  - Il-1 beta-induced post-transition effect of NF-kappaB provides time-dependent
      wave of signals for initial phase of intrapostatic inflammation.
AB  - OBJECTIVE: Our previous findings have shown that systemic administration of
      interleukin (IL)-1 beta induces up-regulation of nuclear factor-kappa B (NF
      kappaB) in mouse prostate tissue that may be responsible for leukocyte
      extravasation into prostate stroma. It has been hypothesized that NF-kappaB plays
      a role in the development of prostatitis, and that NF-kappaB activation might
      provide chemoattractive signals for leukocyte extravasation in the prostate.
      METHODS: IL-1 beta was administrated intravenously, alone or with dexamethasone
      (Dex), to separate groups of C57BL/6J mice. Expression of NF-kappaB,
      chemoattractant receptors, and IL-17F in the prostates of the two groups of mice
      at various time periods following treatment was evaluated and compared. RESULTS:
      IL-1 beta administration up-regulated NF-kappaB/p65 activity in the mouse
      prostate. IL-1 beta administration promoted extravasation and accumulation of
      CD45+ mononuclear cells but not neutrophils in the mouse prostate stroma. IL-1
      beta administration provided earlier (4 hr) CXCR1/IL-8RA receptor expression in
      mouse prostate as a first signal, inducing capillary homing, adhesion, and
      initial extravasation of mononuclear cells into the prostate tissue. IL-1 beta
      administration also induced relatively late (24 hr) up-regulation of VCAM1 in the
      endothelial cells of microvessels and of IL-17F in prostate epithelium and in
      stromal infiltrating leukocytes. Concomitant administration of Dex, a known NF
      kappaB inhibitor, resulted in significantly down-regulated IL-1 beta-induced NF
      kappaB/p65 activity, as well as reduced expression of chemokine receptors and IL
      17F in mouse prostate tissue. CONCLUSION: Systemic IL-1 beta administration
      induces NF-kappaB-responsive genes to promote aberrant NF-kappaB/p65 activity,
      which may be critical in the development of prostatitis through its role in the
      production of chemoattractant signals that promote extravasation and stromal
      accumulation of mononuclear cells (mainly by CXCR1/IL-8RA), and initiation of a
      new wave of pro-inflammatory signals favorable to chronic inflammation (mainly by
      IL-17F).

PMID- 19170129
TI  - Neurotrophic receptor, tropomyosin-related kinase B as an independent prognostic
      marker in gastric cancer patients.
AB  - BACKGROUND AND OBJECTIVES: Neurotrophic receptor tyrosine kinase TrkB has been
      associated with clinical outcome and chemotherapy resistance in neuroblastoma and
      certain human malignancies. Recent studies have focused on the association
      between metastatic potential and TrkB expression in tumor cells. METHODS: To
      determine the role of TrkB in gastric cancer, we analyzed TrkB mRNA levels by
      real-time reverse transcription polymerase chain reaction in 90 patients with
      gastric cancer. TrkB levels were correlated with clinicopathological variables.
      The association between TrkB and overall survival was evaluated by univariate and
      multivariate analyses. RESULTS: The mean TrkB level in gastric cancer tissue was
      2.96 (range, 0-27.1). Thirty-eight (42%) of 90 patients showed detectable TrkB
      levels, whereas the remainder had no detectable TrkB. There was no significant
      association between clinicopathological variables and TrkB positivity. TrkB level
      was significantly associated with extent of lymph node metastasis in node
      positive patients (P = 0.03). TrkB positivity (n = 38) was significantly
      correlated with worse patient survival (P = 0.03). Multivariate analysis showed
      TrkB to be an independent prognostic parameter for overall survival (P = 0.04).
      CONCLUSIONS: TrkB is an independent prognostic marker in patients with gastric
      cancer and appears to be associated with metastatic potential.

PMID- 19170130
TI  - Implemented edge shape of an electrical stimulus capsule.
AB  - BACKGROUND: Recently, a capsule endoscope has been developed and many researchers
      have been trying to develop locomotive capsules. To develop locomotive capsules,
      the inner volume of the capsule has to be large enough to insert actuators, and
      the edge shape of the exterior capsule has to be suitable for locomotion. There
      are many locomotional methods, but an electrical stimulus method provides the
      appropriate power consumption, plus the shape of the capsule is the same as
      general telemetry capsules. In this paper, the optimal shape of the electrical
      stimulus capsule (ESC) was designed and implemented to provide the appropriate
      inner volume and moving speed of the capsule. METHODS: A simple mathematical
      model was used to simulate various capsule shapes, and simple mathematical
      formulae were used to simulate the relationship between the shape of the edge of
      the capsule and the contraction force of the small intestine. The optimal edge
      shape of the capsule was decided based on the crossing point of the volume and
      moving speed. To verify the simulation, two capsules were implemented as the
      control and experimental groups. RESULTS: From the in vitro experiments, four
      fresh intestines were used to measure the moving speed of the capsules. The
      average speed of the proposed capsule was 0.125 +/- 0.096 cm/s (20 V, 10 ms, 20
      Hz), while the control group capsule was only 0.016 +/- 0.33 cm/s (20 V, 10 ms,
      20 Hz), and both groups showed a significant difference from the statistical
      analysis (p < 0.001, Mann-Whitney rank sum test). CONCLUSIONS: This paper
      presents a proposed design for the external shape of the ESC that could fill the
      need of researchers who want more inner volume and doctors who want to prevent
      the capsule from being stuck in the intestine.

PMID- 19170131
TI  - Robust computer-controlled system for intracytoplasmic sperm injection and
      subsequent cell electro-activation.
AB  - INTRODUCTION: Intracytoplasmic sperm injection (ICSI) and the subsequent cell
      electro-activation process is a relatively new enhanced procedure to address male
      factor infertility. The current method involves the engagement of experienced
      embryologists for such a purpose. More advanced methodologies, which use high
      precision instrumentation tools, will speed up the whole procedure. METHODS: In
      this paper, the development of a computer-controlled system for ICSI and the
      subsequent cell electro-activation process is presented. The system is integrated
      to a microinjection workstation and piezo-actuator to perform the ICSI procedure,
      with vision capability to automatically position the components precisely. A
      micro-pump assembly is utilized for automatic medium refreshment and a heater
      plate assembly provides temperature control during the cell electro-activation
      process. The overall system is comprehensive, comprising modular functional
      components integrated within a hardware architecture. RESULTS: Experimental
      results on mice oocytes verified the effectiveness of the developed system over
      the current method. CONCLUSIONS: Further improvements on the instrumentation
      tools will improve the robustness and overall performance of the developed
      system.

PMID- 19170132
TI  - Advanced lung disease: meeting the challenges.

PMID- 19170133
TI  - Adaptively weighted association statistics.
AB  - We investigate methods for testing gene-disease outcome associations in
      situations where the genetic relationship potentially varies among subjects with
      differing environmental or clinical attributes. We propose a strategy which
      modestly increases multiple testing by evaluating weighted test statistics which
      focus (or enrich) association tests within subgroups and use a Monte-Carlo
      method, based on simulating from the approximate large sample distribution of the
      statistics, to control type 1 error. We also introduce a stage-wise calculated
      test statistic which allows more complex weighting on multiple environmental
      variables. Results from simulation studies confirm improved power of the proposed
      approaches compared to marginal testing in many situations.

PMID- 19170134
TI  - Genotype-based matching to correct for population stratification in large-scale
      case-control genetic association studies.
AB  - Genome-wide association studies are helping to dissect the etiology of complex
      diseases. Although case-control association tests are generally more powerful
      than family-based association tests, population stratification can lead to
      spurious disease-marker association or mask a true association. Several methods
      have been proposed to match cases and controls prior to genotyping, using family
      information or epidemiological data, or using genotype data for a modest number
      of genetic markers. Here, we describe a genetic similarity score matching (GSM)
      method for efficient matched analysis of cases and controls in a genome-wide or
      large-scale candidate gene association study. GSM comprises three steps: (1)
      calculating similarity scores for pairs of individuals using the genotype data;
      (2) matching sets of cases and controls based on the similarity scores so that
      matched cases and controls have similar genetic background; and (3) using
      conditional logistic regression to perform association tests. Through computer
      simulation we show that GSM correctly controls false-positive rates and improves
      power to detect true disease predisposing variants. We compare GSM to genomic
      control using computer simulations, and find improved power using GSM. We suggest
      that initial matching of cases and controls prior to genotyping combined with
      careful re-matching after genotyping is a method of choice for genome-wide
      association studies.

PMID- 19170135
TI  - Asymptotic tests of association with multiple SNPs in linkage disequilibrium.
AB  - We consider detecting associations between a trait and multiple single nucleotide
      polymorphisms (SNPs) in linkage disequilibrium (LD). To maximize the use of
      information contained in multiple SNPs while minimizing the cost of large degrees
      of freedom (DF) in testing multiple parameters, we first theoretically explore
      the sum test derived under a working assumption of a common association strength
      between the trait and each SNP, testing on the corresponding parameter with only
      one DF. Under the scenarios that the association strengths between the trait and
      the SNPs are close to each other (and in the same direction), as considered by
      Wang and Elston [Am. J. Hum. Genet. [2007] 80:353-360], we show with simulated
      data that the sum test was powerful as compared to several existing tests;
      otherwise, the sum test might have much reduced power. To overcome the limitation
      of the sum test, based on our theoretical analysis of the sum test, we propose
      five new tests that are closely related to each other and are shown to
      consistently perform similarly well across a wide range of scenarios. We point
      out the close connection of the proposed tests to the Goeman test. Furthermore,
      we derive the asymptotic distributions of the proposed tests so that P-values can
      be easily calculated, in contrast to the use of computationally demanding
      permutations or simulations for the Goeman test. A distinguishing feature of the
      five new tests is their use of a diagonal working covariance matrix, rather than
      a full covariance matrix as used in the usual Wald or score test. We recommend
      the routine use of two of the new tests, along with several other tests, to
      detect disease associations with multiple linked SNPs.

PMID- 19170136
TI  - Crude cacao Theobroma cacao extract reduces mutagenicity induced by
      benzo[a]pyrene through inhibition of CYP1A activity in vitro.
AB  - Polyphenols have been shown to have potent antioxidant activity, and therefore,
      food containing polyphenols is expected to contribute to the prevention of
      cancer. However, food contains not only polyphenols but also various other
      constituents. We used the Ames test to investigate the effects of crude extracts
      of whole cacao products, which are known to be rich in polyphenols, on the
      mutagenicity of benzo[a]pyrene (B[a]P) in Salmonella typhimurium strain TA 98 and
      tert-butyl hydroperoxide (t-BuOOH) in S. typhimurium strain TA 102. B[a]P induces
      mutagenicity by metabolic activation and t-BuOOH induces it by generation of free
      radicals. While white chocolate did not modulate the numbers of revertant
      colonies produced by B[a]P treatment, milk chocolate and cacao powder extracts
      did. On the other hand, surprisingly, none of the cacao products tested affected
      the number of revertant colonies when t-BuOOH was used as the mutagen. At maximum
      concentration (13.25 mg cacao powder/ml), the crude cacao powder extract reduced
      ethoxyresorufin O-deethylase activity to 17.4% of the control, suggesting that
      whole cacao products inhibit cytochrome P450 (CYP) 1A activity. In conclusion,
      inhibition of CYP1A activity by cacao products may prevent DNA damage by reducing
      metabolic activation of carcinogens.

PMID- 19170137
TI  - Amelioration of metformin-induced hypothyroidism by Withania somnifera and
      Bauhinia purpurea extracts in Type 2 diabetic mice.
AB  - An investigation was carried out to reveal the possible ameliorative role of two
      plant extracts on an antidiabetic drug-induced hypothyroidism in Type 2 diabetic
      animals. Dexamethasone (1.0 mg/kg, i.m.) administration caused hyperglycemia with
      a parallel increase in renal lipid peroxidation (LPO), relative risk ratio (RR),
      and the concentrations of serum insulin; total cholesterol (TC); low-density
      lipoprotein cholesterol (LDL-C); very low-density lipoprotein cholesterol (VLDL
      C) and triglycerides (TG). It decreased serum triiodothyronine (T3), thyroxine
      (T4) and high-density lipoprotein cholesterol (HDL-C) levels as well as renal
      superoxide dismutase (SOD); catalase (CAT) and reduced glutathione (GSH) content.
      Administration with metformin (150 mg/kg, orally) to diabetic animals further
      reduced circulating T4 level and caused severe hypothyroidism. It also reduced
      renal LPO, RR, serum concentrations of insulin; glucose and LDL-C with a parallel
      increase in cellular antioxidants. While oral administration with either Withania
      somnifera (1.4 g/kg) or Bauhinia purpurea (2.5 mg/kg) extract along with
      dexamethasone and metformin elevated the concentrations of circulating T3 and T4
      to euthyroid level. The plant extracts also corrected RR ratio and serum
      concentration of lipids. The findings of the present study, for the first time,
      reveal that the evaluated plant extracts have a potential to ameliorate metformin
      induced hypothyroidism in Type 2 diabetic subjects.

PMID- 19170138
TI  - Activation of macrophages by polysaccharide-protein complex from Lycium barbarum
      L.
AB  - Macrophages play crucial roles in innate immunity. This paper reports that a
      polysaccharide-protein complex isolated from Lycium barbarum (LBP) is able to
      activate macrophages. LBP was isolated from Lycium barbarum fruit and separated
      to five homogenous fractions, designated LBPF1, LBPF2, LBPF3, LBPF4 and LBPF5. It
      was found that LBP (50 mg/kg, i.p.) markedly upregulated the expressions of CD40,
      CD80, CD86 and MHC class II molecules on peritoneal macrophages. In vitro studies
      showed that LBP and LBPF1-5 activated transcription factors NF-kappaB and AP-1 by
      RAW264.7 macrophage cells, induced TNF-alpha, IL-1beta, IL-12p40 mRNA expression,
      and enhanced TNF-alpha production in a dose-dependent manner. Furthermore, LBP
      (50 mg/kg, i.p.) significantly enhanced macrophage endocytic and phagocytic
      capacities in vivo. These results indicate that LBP enhances innate immunity by
      activating macrophages. The mechanism may be through activation of transcription
      factors NF-kappaB and AP-1 to induce TNF-alpha production and upregulation of MHC
      class II costimulatory molecules.

PMID- 19170139
TI  - Pomegranate extract mouth rinsing effects on saliva measures relevant to
      gingivitis risk.
AB  - Pomegranate components have properties that could promote oral health, including
      reducing the risk of gingivitis. The present study examined young adults (n = 32,
      split evenly among both genders), for the effects of 4 weeks of thrice daily
      mouth rinsing with the pomegranate (Punica granatum L.) extract PomElla dissolved
      in water. This treatment changed salivary measures relevant to oral health
      including gingivitis. The changes were: reduced total protein (which can
      correlate with plaque forming bacteria readings), reduced activities of aspartate
      aminotransferase (an indicator of cell injury), reduced alpha-glucosidase
      activity (a sucrose degrading enzyme), increased activities of the antioxidant
      enzyme ceruloplasmin (which could give better protection against oral oxidant
      stress) and increased radical scavenging capacity (though this increase was
      significant only by nonparametric statistical analysis). A placebo of cornstarch
      in water did not affect these measures. These data raise the possibility of using
      pomegranate extracts in oral health products such as toothpaste and mouthwashes.

PMID- 19170140
TI  - In vitro and in vivo antiproliferative activity of laherradurin and cherimolin-2
      of Annona diversifolia Saff.
AB  - Acetogenins from Annonaceae (ACG) are potent inhibitors of the mitochondrial
      complex I, they present cytotoxic activity on neoplasic lines, including those
      with multiresistance to drugs. In vivo antitumor activities of some ACG have been
      reported; however, no information is available regarding the relationship between
      their cytotoxic activity in cell cultures and their antiproliferative action in
      vivo. Laherradurin and cherimolin-2 acetogenins were isolated from Annona
      diversifolia seeds, and their inhibitory potential was analysed in vitro on HeLa
      and SW-480 cells. Doses containing 1, 10, 100 and 500 times the IC50 obtained
      from the proliferation assays and multiplied by the weight of the animal, were
      injected once daily into athymic mice bearing these cancer cell lines; their
      effect upon tumor growth was measured over a period of 20 days. Laherradurin was
      more active than cherimolin-2, and it showed in in vitro proliferation assays a
      similar IC50 in both neoplasic lines. In athymic mice, laherradurin administered
      in 10x, 100x and 500x doses, reduced the size of HeLa tumors, and with 100x and
      500x doses, affected the SW-480 tumor development. These doses were similar to
      results found with the control drug doxorubicin (p < or = 0.05). On the other
      hand, cherimolin-2 had an effect on HeLa tumors cells at 100x and 500x doses (p <
      or = 0.05).

PMID- 19170142
TI  - Chemical composition and biological potential of plants from the genus Bauhinia.
AB  - Plants of the genus Bauhinia (Fabaceae, Leguminosae), commonly known as cow's-paw
      or cow's hoof, are widely distributed in most tropical countries and have been
      used frequently in folk medicine to treat different kinds of pathologies,
      particularly diabetes, infections, as well as pain and inflammation. In recent
      years, interest in these plants has increased considerably throughout the world.
      The biological properties of different phytopreparations and pure metabolites
      have been investigated in numerous experimental in vivo and in vitro models.
      Although some contradicting evidence has been documented, in general, the results
      support the reported therapeutic properties, indicating that they are mainly due
      to the presence of flavonoids. This review summarizes the recent chemical and
      biological knowledge of plants of the genus Bauhinia.

PMID- 19170141
TI  - Mesenchymal progenitor cells derived from traumatized human muscle.
AB  - Mesenchymal stem cells (MSCs) derived from adult tissues are an important
      candidate cell type for cell-based tissue engineering and regenerative medicine.
      Currently, clinical applications for MSCs require additional surgical procedures
      to harvest the autologous MSCs (i.e. from bone marrow) or commercial allogeneic
      alternatives. We have recently identified a population of mesenchymal progenitor
      cells (MPCs) in traumatized muscle tissue that has been surgically debrided from
      traumatic orthopaedic extremity wounds. The purpose of this study was to evaluate
      whether MPCs derived from traumatized muscle may provide a clinical alternative
      to bone-marrow MSCs, by comparing their morphology, proliferation capacity, cell
      surface epitope profile and differentiation capacity. After digesting the muscle
      tissue with collagenase, the MPCs were enriched by a direct plating technique.
      The morphology and proliferation rate of the muscle-derived MPCs was similar to
      bone-marrow derived MSCs. Both populations expressed cell surface markers
      characteristic for MSCs (CD 73, CD 90 and CD105), and did not express markers
      typically absent on MSCs (CD14, CD34 and CD45). After 21 days in specific
      differentiation media, the histological staining and gene expression of the MPCs
      and MSCs was characteristic for differentiation into osteoblasts, chondrocytes
      and adipocytes, but not into myoblasts. Our findings demonstrate that traumatized
      muscle-derived MPCs exhibit a similar phenotype and resemble MSCs derived from
      the bone marrow. MPCs harvested from traumatized muscle tissue may be considered
      for applications in tissue engineering and regenerative medicine following
      orthopaedic trauma requiring circumferential debridement.

PMID- 19170143
TI  - The clinical investigation of Citrullus colocynthis (L.) schrad fruit in
      treatment of Type II diabetic patients: a randomized, double blind, placebo
      controlled clinical trial.
AB  - Citrullus colocynthis (L.) Schrad fruit is an herbal medicine used by traditional
      herbalists for the treatment of diabetes in Iran. To determine its efficacy and
      toxicity, a 2 month clinical trial was conducted in 50 type II diabetic patients.
      Two groups of 25 each under standard antidiabetic therapy, received 100 mg C.
      colocynthis fruit capsules or placebos three times a day, respectively. The
      patients were visited monthly and glycosylated hemoglobin (HbA1c), fasting blood
      glucose, total cholesterol, LDL, HDL, triglyceride, aspartate transaminase,
      alanine transaminase, alkaline phosphatase, urea and creatinine levels were
      determined at the beginning and after 2 months. The results showed a significant
      decrease in HbA1c and fasting blood glucose levels in C. colocynthis treated
      patients. Other serological parameters levels in both the groups did not change
      significantly. No notable gastrointestinal side effect was observed in either
      group. In conclusion, C. colocynthis fruit treatment had a beneficial effect on
      improving the glycemic profile without severe adverse effects in type II diabetic
      patients. Further clinical studies are recommended to evaluate the long-term
      efficacy and toxicity of C. colocynthis in diabetic patients.

PMID- 19170144
TI  - Antiproliferative activity of Hungarian Asteraceae species against human cancer
      cell lines. Part II.
AB  - The antiproliferative activities of aqueous and organic extracts prepared from 26
      Hungarian species of the tribes Cynereae and Lactuceae (Asteraceae) were tested
      in vitro against HeLa (cervix epithelial adenocarcinoma), A431 (skin epidermoid
      carcinoma) and MCF7 (breast epithelial adenocarcinoma) cells by using the MTT
      assay. Of the tested 200 extracts of different plant parts obtained with n
      hexane, chloroform, 50% methanol and water, 16 extracts displayed noteworthy cell
      growth inhibitory activity (>50% inhibition at a concentration of 10 microg/mL).
      The IC50 values of these extracts were determined, and their direct cytotoxic
      effects were measured. High differences between the antiproliferative and
      cytotoxic activities, demonstrating a real cell proliferation inhibitory activity
      rather than direct killing effects, were found for some Centaurea, Cirsium,
      Cichorium, Lactuca, Onopordum and Scorsonera extracts.

PMID- 19170145
TI  - The influence of adaptogens on ultraweak biophoton emission: a pilot-experiment.
AB  - In the present study, the effect of plant adaptogens (Rhodiola rosea and ADAPT
      232) on human photon emission has been determined. In a randomized double blind
      placebo-controlled study, 30 subjects were randomly assigned to three groups: one
      group (n = 10) taking placebo pills, one group (n = 10) taking Rhodiola rosea
      (SHR-5) pills and one group (n = 10) taking ADAPT-232 supplements (the latter
      being a fixed combination of the following three adaptogens: Eleutherococcus
      senticosus, Rhodiola rosea and Schisandra chinensis). All subjects underwent
      measurements to determine ultra-weak photon emission (UPE) of the dorsal side of
      their hands using a photon-counting device, both before and after a week of
      taking the supplements. In addition, the experienced levels of stress and fatigue
      (tiredness) were evaluated. After 1 week of supplementation, the Rhodiola group
      showed a significant decrease (p = 0.027) in photon emission in comparison with
      the placebo group. Furthermore, after supplementation, a significant decrease (p
      = 0.049) concerning the experienced level of fatigue in the Rhodiola group was
      observed compared with the placebo group. No significant changes were observed
      between the ADAPT-232 and the placebo group.

PMID- 19170147
TI  - Direct decomposition of nitrous oxide to nitrogen by in situ oxygen removal with
      a perovskite membrane.
AB  - Direct decomposition of N(2)O to N(2) using perovskite hollow fiber membranes is
      achieved by combination with in situ oxygen removal (see picture). A coupled
      partial methane oxidation allows N(2)-free synthesis gas to be obtained. This
      sustainable process combines N(2)O removal with the simultaneous production of
      valuable chemicals.

PMID- 19170146
TI  - In vitro formation of phase I and II metabolites of propranolol and determination
      of their structures using chemical derivatization and liquid chromatography
      tandem mass spectrometry.
AB  - Derivatization with 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC) has been
      successfully used as a tool to differentiate between aromatic and aliphatic O
      glucuronides of hydroxypropranolol. The analyses were performed with liquid
      chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS)
      with both a triple quadrupole and an ion trap instrument. Hydroxylated forms of
      propranolol can be glucuronidated in aliphatic as well as aromatic positions.
      These isoforms are not distinguishable by tandem MS alone, as they both initially
      lose 176 Da, i.e. monodehydrated glucuronic acid, giving back the aglycone. Two
      in vitro systems were set up for the production of propranolol metabolites. The
      obtained isomers of 4'-hydroxypropranolol glucuronide were determined to
      correspond to one aliphatic and one aromatic form, using chemical derivatization
      with DMISC and LC-MS(n). DMISC was shown to react with the secondary amine in the
      case where the naphtol was occupied by the glucuronyl moiety, resulting in a
      different fragmentation pattern compared with that of the aliphatic glucuronide,
      where the naphtol group was accessible to derivatization.

PMID- 19170148
TI  - Carbohydrate-2-deoxy-2-phosphonates: simple synthesis and Horner-Emmons reaction.
AB  - Phosphorus meets carbohydrates: Dimethyl phosphite reacts with ceric(IV) ammonium
      nitrate (CAN) to give phosphonyl radicals that add to glycals 1. The derivatives
      2 were isolated in high yields and during a subsequent Horner-Emmons reaction
      underwent an interesting elimination to give 3,6-dihydro-2H-pyrans 3. The short
      sequence with simple precursors is applicable to the transformation of hexoses,
      pentoses, and disaccharides. Bn = benzyl.

PMID- 19170149
TI  - Nanophotonic ion production from silicon microcolumn arrays.
AB  - Nanoantennas for ions: Silicon microcolumn arrays harvest light from a laser
      pulse to produce ions. The system behaves like a quasi-periodic antenna array
      with ion yields that show profound dependence on the plane of polarization and
      the angle of incidence of the laser beam. Photonic ion sources promise to enable
      enhanced control of ion production on a micro- and nanometer scale and direct
      integration with miniaturized analytical devices.

PMID- 19170150
TI  - Revisiting prussian blue analogues with solid-state MAS NMR spectroscopy: spin
      density and local structure in [Cd3{Fe(CN)6}2] x 15 H2O.
AB  - No legendary Prussian order! The distribution of vacancies in Prussian blue
      analogues is not random, and the spin density on the Cd(2+) ion varies depending
      on the number of paramagnetic ions in its surroundings. This conclusion follows
      from (113)Cd solid-state magic-angle spinning NMR studies of
      [Cd(3){Fe/Co(CN)(6)}(2)] x 15 H(2)O, where the presence of small but significant
      spin density on the observed (113)Cd nucleus leads to improved spectral
      resolution.

PMID- 19170151
TI  - Sequential synthesis of furans from alkynes: successive ruthenium(II)- and
      copper(II)-catalyzed processes.
AB  - Step in time: 2,5-Disubstituted furans can be prepared from terminal alkynes in
      one pot using two successive catalytic reactions (see scheme; p-TSA = para
      toluenesulfonic acid). First, a 1,3-dienyl alkyl ether is produced by the
      dimerization of a terminal alkyne and addition of an alcohol catalyzed by
      [RuCp*(NCMe)(3)][PF(6)]. Then, consecutive hydrolysis and cyclization catalyzed
      by CuCl(2) provides the 2,5-disubstituted furan.

PMID- 19170152
TI  - Oxindole synthesis by direct coupling of C(sp2)-H and C(sp3)-H centers.
AB  - An sp(2)/sp(3) get-together: A novel and efficient method can be used to
      synthesize 3,3-disubstitued oxindoles by the direct intramolecular oxidative
      coupling of an aryl C(sp(2))-H and a C(sp(3))-H center (see scheme; DMF = N,N
      dimethylformamide).

PMID- 19170153
TI  - Room-temperature palladium-catalyzed C-H activation: ortho-carbonylation of
      aniline derivatives.
AB  - Pd and CO--ureally got me! The title reaction proceeds efficiently at 18 degrees
      C under CO (1 atm) with 5 % [Pd(OTs)(2)(MeCN)(2)] as precatalyst. Depending on
      the solvents used, either anthranilates or cyclic imides can be obtained in high
      yields (see picture, BQ = benzoquinone, Ts = 4-toluenesulfonyl).

PMID- 19170154
TI  - Control of duplex formation and columnar self-assembly with heterogeneous
      amide/urea macrocycles.
AB  - The perfect blend: A new class of self-assembling cyclooligomers with mixed
      urea/amide backbone is described (see figure). A high level of hierarchical and
      directional control is achieved: depending on the level of backbone
      preorganization, columnar or tubular arrangements with either parallel or
      antiparallel growing modes can be selected.

PMID- 19170155
TI  - In vitro inhibition of CYP3A4 by herbal remedies frequently used by cancer
      patients.
AB  - The herbal remedies Natto K2, Agaricus, mistletoe, noni juice, green tea and
      garlic, frequently used by cancer patients, were investigated for their in vitro
      inhibition potential of cytochrome P-450 3A4 (CYP3A4) metabolism. To our
      knowledge, only garlic and green tea had available data on the possible
      inhibition of CYP3A4 metabolism. Metabolic studies were performed with human c
      DNA baculovirus expressed CYP3A4. Testosterone was used as a substrate and
      ketoconazole as a positive quantitative inhibition control. The formation of 6
      beta-OH-testosterone was quantified by a validated HPLC methodology. Green tea
      was the most potent inhibitor of CYP3A4 metabolism (IC(50): 73 microg/mL),
      followed by Agaricus, mistletoe and noni juice (1324, 3594, >10 000 microg/mL,
      respectively). All IC(50) values were high compared with those determined for
      crude extracts of other herbal remedies. The IC(50)/IC(25) ratios for the
      inhibiting herbal remedies ranged from 2.15 to 2.67, indicating similar
      inhibition profiles of the herbal inhibitors of CYP3A4. Garlic and Natto K2 were
      classified as non-inhibitors. Although Agaricus, noni juice, mistletoe and green
      tea inhibited CYP3A4 metabolism in vitro, clinically relevant systemic or
      intestinal interactions with CYP3A4 were considered unlikely, except for a
      probable inhibition of intestinal CYP3A4 by the green tea product.

PMID- 19170156
TI  - Comparison of enteroprotective efficacy of triphala formulations (Indian Herbal
      Drug) on methotrexate-induced small intestinal damage in rats.
AB  - Triphala is categorized as a rejuvenator and antioxidant-rich Ayurvedic herbal
      formulation and has traditionally been used in various gastric problems including
      intestinal inflammation. The aim of the present study was to examine the
      comparative enteroprotective effect of Triphala formulations against methotrexate
      induced intestinal damage in rats. Triphala formulations were prepared by mixing
      equal (1:1:1) and unequal (1:2:4) proportions of Terminalia chebula Retz.,
      Terminalia belerica (Gaertn.) Roxb. and Emblica officinalis Gaertn. Intestinal
      damage was induced by administering methotrexate (MTX) in a dose of 12 mg/kg,
      orally for 4 days to albino rats. The intestinal damage response was assessed by
      gross and microscopical injury, measuring the intestinal permeability to phenol
      red and tissue biochemical parameters. Triphala equal and unequal formulations at
      the dose of 540 mg/kg significantly restored the depleted protein level in brush
      border membrane of intestine, phospholipid and glutathione content and decreased
      the myeloperoxidase and xanthine oxidase level in intestinal mucosa of
      methotrexate-treated rats. In addition, Triphala unequal formulation showed
      significant decrease in permeation clearance of phenol red with significant
      attenuation in the histopathological changes, level of disaccharidase in brush
      border membrane vesicles and lipid peroxidation content of intestinal mucosa.
      Based on the data generated, it is suggested that Triphala unequal formulation
      provides significantly more protection than Triphala equal formulation against
      methotrexate-induced damage in rat intestine.

PMID- 19170157
TI  - Antifungal activity of Glycyrrhiza glabra extracts and its active constituent
      glabridin.
AB  - Glabridin, an active constituent of Glycyrrhiza glabra roots, was found to be
      active against both yeast and filamentous fungi. Glabridin also showed resistance
      modifying activity against drug resistant mutants of Candida albicans at a
      minimum inhibitory concentration of 31.25-250 microg/mL. Although the compound
      was reported earlier to be active against Candida albicans, but this is the first
      report of its activity against drug resistant mutants.

PMID- 19170158
TI  - Modulatory influence of prepubertal biochanin A exposure on mammary gland
      differentiation and expression of estrogen receptor-alpha and apoptotic proteins.
AB  - The modulatory influence of the phytoestrogen biochanin A, an isoflavinoid found
      in red clover (Trifolium pratense), on the differentiation and proliferation of
      mammary epithelial cells and the expression of estrogen receptor-alpha (ER-alpha)
      in female prepubertal Sprague-Dawley rat mammary glands was examined, for which
      there have been no reports to date. Biochanin A (500 microg/g bw) was injected
      subcutaneously on days 16, 18 and 20 post-partum. The mammary gland was dissected
      out and terminal end buds, terminal ducts and lobules were counted. ER-alpha,
      Bcl2, Bax and caspase-3 expression were determined by immunohistochemistry.
      Estradiol benzoate (EB) (500 ng/g bw) and dimethyl sulphoxide (DMSO) were used as
      the reference and vehicle, respectively. The results showed a significant
      enhancement of differentiation at post-natal day (PND) 21 as well as at PND 50 in
      the mammary glands. There was a significant decrease of ER-alpha expression at
      PND 21 and an increased expression of the same at PND 50, whereas increased
      proliferation at PND 21 and increased apoptosis at PND 50 in the mammary glands
      were observed in biochanin A treated animals. The mode and magnitude of the
      effect of biochanin A was almost similar to that of EB. These findings suggested
      that prepubertal exposure to biochanin A modulated the regulatory processes and
      in turn enhanced the differentiation and development of mammary glands in female
      rats. These observations may have significance in human health.

PMID- 19170159
TI  - Evaluation of the osteogenic potential and vascularization of 3D
      poly(3)hydroxybutyrate scaffolds subcutaneously implanted in nude rats.
AB  - The aim of this study was to evaluate the osteogenic potential and the
      vascularization of embroidered, tissue engineered, and cell-seeded 3D
      poly(3)hydroxybutyrate (PHB) scaffolds in nude rats. Collagen I (coll I)- and
      collagen I/chondroitin sulfate (coll I/CS)-coated PHB scaffolds were seeded with
      human mesenchymal stem cells (hMSCs). Proliferation and differentiation were
      characterized by different biochemical assays in vitro. For animal experiments,
      the cells were cultivated on coll I- or coll I/CS-coated scaffolds and either
      expanded or osteogenically differentiated. Scaffolds were piled up to create a 3D
      scaffold pad and implanted subcutaneously into nude rats. In vitro hMSC showed
      proliferation and differentiation on PHB scaffolds. Alkaline phosphatase (ALP)
      and calcium increased in the differentiation medium and in the presence of coll
      I/CS. In vivo blood vessels were found in the scaffold-stack.
      Histological/immunohistological analyses of explanted scaffolds showed osteogenic
      markers such as osteopontin, osteonectin, and coll I around the PHB fibers. Coll
      I/CS-coated scaffolds with expanded hMSC showed higher values of ALP and calcium
      than the other combinations. Embroidered PHB scaffolds, coated with extracellular
      matrix components, provided an adequate environment and, therefore, a template
      for hMSC which could be differentiated in osteogenic direction.

PMID- 19170160
TI  - LEEM investigations of surfaces using a beam of energetic self-ions.
AB  - This article reviews recent research using a low-energy electron microscope,
      built by Tromp at IBM, and equipped with an accelerator that permits in situ
      irradiation with a beam of self-ions. The available ion energies of 20 eV to 5
      keV span the range from epitaxial growth by a hyperthermal beam to sputtering at
      the level of approximately 10 atoms per incident ion. The design criteria and
      instrument calibration are described. The research described is surface science
      that requires a vacuum maintained below 10(-10) Torr, with all components
      contained in the same vacuum. Two general categories of applications are
      sketched. Experiments that accurately measure important physical quantities
      include surface mass diffusion over an extended temperature range; determining
      the critical chemical potential at which island nucleation occurs; observation
      and explanation of the universal evolution by which adatom and advacancy islands
      both grow and shrink by beam-driven processes; and the study of sublimation
      (regarded as negative ion beam intensity). Experiments described here with other
      goals include beam-assisted synthesis first of large pans and mesas for isolating
      surface experiments (e.g., nucleation) from the surrounding crystal, and second
      of Fourier waves on steps, for studies of diffusive relaxation. Operation of
      exotic structures including Bardeen-Herring sources and Frank growth spirals
      deformed by crystal anisotropy are also described.

PMID- 19170161
TI  - Transferring knowledge and experience: training and supervision.
AB  - The authors describe practitioners' professional development, the challenges and
      dilemmas that they confront, and the support they receive in their work. They
      focus on examples of supervision sessions and describe typical dilemmas and
      solutions that come up during these sessions. These examples reflect four main
      themes that were identified as receiving much attention from practitioners over
      the years: boundaries and role definitions; relationships with students,
      teachers, and parents; extent of responsibility; and professional questions.
      Finally, the authors present an interview with a RALLY supervisor that
      illustrates typical dilemmas and conflicts that practitioners face during their
      work.

PMID- 19170162
TI  - Disposition of axonal caspr with respect to glial cell membranes: Implications
      for the process of myelination.
AB  - Neurofascin-155 (NF155) and caspr are transmembrane proteins found at discrete
      locations early during development of the nervous system. NF155 is present in the
      oligodendrocyte cell body and processes, whereas caspr is on the axonal surface.
      In mature nerves, these proteins are clustered at paranodes, flanking the node of
      Ranvier. To understand how NF155 and caspr become localized to the paranodal
      regions of myelinated nerves, we have studied their distribution over time in
      myelinating cultures. Our observations indicate that these two proteins are
      recruited to the cell surface at the contact zone between axons and
      oligodendrocytes, where they trans-interact. This association explains the early
      pattern of caspr distribution, a helical coil that winds around the axon,
      resembling the turns of the myelin sheath. Caspr, an axonal membrane protein,
      therefore seems to move in register with the overlying myelinating cell via its
      interactions with myelin proteins. We suggest that NF155 is the glial cell
      membrane protein responsible for caspr distribution. The pair act as interacting
      partners on either side of the axoglial contact area. Most likely, there are
      other proteins on the axonal surface whose distribution is equally influenced by
      interaction with the nascent myelin sheath. The fact that caspr follows the
      movement of the spiraling membrane has a direct affect on the interpretation of
      the way in which myelin is formed.

PMID- 19170163
TI  - Changes of cognition and regional cerebral activity during acute hypoglycemia in
      normal subjects: A H2 15O positron emission tomographic study.
AB  - Blurred vision and cognitive difficulties are prominent symptoms during acute
      insulin-induced hypoglycemia. Our hypothesis was that changes in cerebral
      activity reflect these symptoms. Positron emission tomography (PET) with oxygen
      15-labelled water was used to measure relative changes in regional cerebral blood
      flow (rCBF) as a marker of cerebral activity. Hypoglycemia was induced by
      intravenous insulin infusion in 19 healthy men performing two different cognitive
      tasks of varying complexity. The hypoglycemic stimulus [plasma glucose 2.2
      mmol/liter (0.4)] produced a significant hormonal counterregulatory response.
      During the low cognitive load, rCBF decreased in response to hypoglycemia in a
      large bilateral area in the posterior part of the temporal lobe, and rCBF
      increased bilaterally in the anterior cingulate gyrus, the right frontal gyrus,
      the fusiform gyrus, thalamus, and the left inferior part of the frontal gyrus.
      During the high cognitive load, rCBF decreased bilaterally in a large region in
      the posterior part of the temporal gyrus and increased in the left and right
      anterior cingulate gyrus, left and right frontal gyrus, right parahippocampal and
      lingual gyrus, and left superior temporal gyrus. Visual impairment during
      hypoglycemia was associated with deactivation in the ventral visual stream. The
      anterior cingulate gyrus was activated during hypoglycemia in a load-dependent
      manner. Areas on the frontal convexity were differentially activated in response
      to the cognitive load during hypoglycemia. Our findings suggest that hypoglycemia
      induces changes in sensory processing in a cognition-independent manner, whereas
      activation of areas of higher order functions is influenced by cognitive load as
      well as hypoglycemia.

PMID- 19170164
TI  - Large-volume-apheresis facilitates autologous transplantation of hematopoietic
      progenitors in poor mobilizer patients.
AB  - Given that pre-apheresis CD34(+) cell count (PA-CD34) predicts the apheresis'
      yield, a minimum of 5 to 20 PA-CD34/microl is required in many institutions to
      initiate cell collection. The aim of this study was to clarify whether large
      volume-apheresis (LVA) could facilitate progenitor cell transplantation in
      patients with low PA-CD34. Apheresis was initiated in 226 patients, disregarding
      PA-CD34, at days: +5 in G-CSF, +10 in cyclophosphamide+G-CSF, and +15 to +20 in
      other chemotherapy+G-CSF mobilization, when leucocytes >2.5 x 10(9)/L. Four times
      the blood volume was processed. Patients were grouped according to their PA-CD34:
      >or=10/microl (group-A, n = 143); <10/microl but >or=5/microl (group-B, n = 40)
      and <5/microl (group-C, n = 43). No differences were found in diagnoses, gender,
      age, previous treatments or mobilization regimen between groups. Enough CD34(+)
      cells (>1.9 x 10(6)/kg) were obtained in 31 patients (72%) from group-C, although
      in this group two mobilizations were needed in 20 patients (46.5%), compared to 5
      (3.5%) and 1 (2.5%) in groups A and B, respectively (P < 0.01). Evenly three
      apheresis or more were required in 28 patients (65.1%) from group-C, compared to
      8 (5.6%) and 6 (15.0%) in groups A and B, respectively (P < 0.01). In conclusion
      LVA can facilitate autologous transplantation in poor-mobilizer-patients, low PA
      CD34 should not be an inflexible exclusion factor.

PMID- 19170165
TI  - Glucose-dependent insulinotropic polypeptide (GIP) and its receptor (GIPR):
      cellular localization, lesion-affected expression, and impaired regenerative
      axonal growth.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) was initially described to be
      rapidly regulated by endocrine cells in response to nutrient ingestion, with
      stimulatory effects on insulin synthesis and release. Previously, we demonstrated
      a significant up-regulation of GIP mRNA in the rat subiculum after fornix injury.
      To gain more insight into the lesion-induced expression of GIP and its receptor
      (GIPR), expression profiles of the mRNAs were studied after rat sciatic nerve
      crush injury in 1) affected lumbar dorsal root ganglia (DRG), 2) spinal cord
      segments, and 3) proximal and distal nerve fragments by means of quantitative RT
      PCR. Our results clearly identified lesion-induced as well as tissue type
      specific mRNA regulation of GIP and its receptor. Furthermore, comprehensive
      immunohistochemical stainings not only confirmed and exceeded the previous
      observation of neuronal GIP expression but also revealed corresponding GIPR
      expression, implying putative modulatory functions of GIP/GIPR signaling in adult
      neurons. In complement, we also observed expression of GIP and its receptor in
      myelinating Schwann cells and oligodendrocytes. Polarized localization of GIPR in
      the abaxonal Schwann cell membranes, plasma membrane-associated GIPR expression
      of satellite cells, and ependymal GIPR expression strongly suggests complex cell
      type-specific functions of GIP and GIPR in the adult nervous system that are
      presumably mediated by autocrine and paracrine interactions, respectively.
      Notably, in vivo analyses with GIPR-deficient mice suggest a critical role of
      GIP/GIPR signal transduction in promoting spontaneous recovery after nerve crush,
      insofar as traumatic injury of GIPR-deficient mouse sciatic nerve revealed
      impaired axonal regeneration compared with wild-type mice.

PMID- 19170166
TI  - NMDA receptor-dependent signaling pathways that underlie amyloid beta-protein
      disruption of LTP in the hippocampus.
AB  - Alzheimer's disease (AD), the most common neurodegenerative disease in the
      elderly population, is characterized by the hippocampal deposition of fibrils
      formed by amyloid beta-protein (A beta), a 40- to 42-amino-acid peptide. The
      folding of A beta into neurotoxic oligomeric, protofibrillar, and fibrillar
      assemblies is believed to mediate the key pathologic event in AD. The hippocampus
      is especially susceptible in AD and early degenerative symptoms include
      significant deficits in the performance of hippocampal-dependent cognitive
      abilities such as spatial learning and memory. Transgenic mouse models of AD that
      express C-terminal segments or mutant variants of amyloid precursor protein, the
      protein from which A beta is derived, exhibit age-dependent spatial memory
      impairment and attenuated long-term potentiation (LTP) in the hippocampal CA1 and
      dentate gyrus (DG) regions. Recent experimental evidence suggests that A beta
      disturbs N-methyl-D-aspartic acid (NMDA) receptor-dependent LTP induction in the
      CA1 and DG both in vivo and in vitro. Furthermore, these studies suggest that A
      beta specifically interferes with several major signaling pathways downstream of
      the NMDA receptor, including the Ca(2+)-dependent protein phosphatase
      calcineurin, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), protein
      phosphatase 1, and cAMP response element-binding protein (CREB). The influence of
      A beta on each of these downstream effectors of NMDA is reviewed in this article.
      Additionally, other mechanisms of LTP modulation, such as A beta attenuation of
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor currents, are
      briefly discussed.

PMID- 19170167
TI  - Cervicovaginal cytological abnormalities in patients with human immunodeficiency
      virus infection, in relation to disease stage, CD4 cell count and viral load.
AB  - The objective of the present study was to assess infections and cytologic
      abnormalities in cervicovaginal smears from 153 HIV-positive women and 169 HIV
      negative followed up at the UFTM School of Medicine between May 1999 and May
      2002. The medical records and cervicovaginal smears were reviewed and the HIV
      positive group was classified according to CD4 cell count, HIV viral load,
      antiretroviral therapy and HIV subgroups (with or without disease; with or
      without therapy) and compared to HIV-negative group. We conclude that the
      frequency of Candida sp, Trichomonas vaginalis and bacterial vaginosis in
      cervicovaginal smear, is not different between HIV-positive and HIV-negative
      women, even if the HIV-group is subdivided according to CD4 cell count, HIV viral
      load, antiretroviral therapy and HIV subgroups. The frequency of LSIL, in
      cervicovaginal smears, was greater in the HIV-group (17.6%) than in the HIV
      negative (4.1%); there was no difference between the two groups according to
      frequency of HSIL (4.6% versus 1.8%), ASCUS/AGUS (7.8% versus 3.5%) and invasive
      carcinoma (1.3% versus 0.6%). The frequency of LSIL was greater in the HIV
      positive group with CD4 cell count < 350 cells/mm(3). The viral load, therapeutic
      regimen and HIV subgroups (HIV-positive without therapy, HIV-positive with
      therapy, AIDS by immunological criteria and AIDS by clinical criteria) have not
      shown relationship with LSIL frequency, until now.

PMID- 19170168
TI  - Cytological features of signet-ring cell carcinoma of the lung: comparison with
      the goblet-cell-type adenocarcinoma of the lung.
AB  - Signet-ring cell carcinoma (SRCC) and goblet-cell-type adenocarcinoma (GCA) are
      mucin-producing lung adenocarcinomas. Primary SRCC shows an aggressive clinical
      course, whereas GCA shows infrequent distant metastasis, but more frequent
      intrapulmonary metastases resembling lobar pneumonia. To distinguish SRCC from
      GCA, this study investigated the respective cytological features of these
      lesions. We selected 10 cases each of SRCC and GCA from the archival imprint
      smears. We assessed them for the following 10 cytological features.
      Necrosis/debris was observed in 60% of the SRCC and 90% of the GCA. A mucinous
      background was observed in 10% of the SRCC and 90% of the GCA. Significant
      inflammation was observed in none of the SRCC and 80% of the GCA. Stromal cluster
      was observed in 30% of the SRCC and 70% of the GCA. Nuclear overlapping was
      observed in 50% of the SRCC and in all of the GCA. Single tumor cells were
      observed in 80% of the SRCC and 10% of the GCA. Honeycomb-like cluster was
      observed in none of the SRCC and 80% of the GCA. Prominent nucleolus was observed
      in 50% of the SRCC and 40% of the GCA. Nuclear membrane irregularity was observed
      in 70% of SRCC and 60% of the GCA. Nuclear pleomorphism was observed in all of
      the SRCC and none of the GCA. The cytological features of SRCC were the presence
      of single tumor cells and nuclear pleomorphism, whereas that of GCA were the
      presence of abundant mucin and significant inflammation in the background, and a
      honeycomb-like cluster.

PMID- 19170169
TI  - Value of P63 and CK5/6 in distinguishing squamous cell carcinoma from
      adenocarcinoma in lung fine-needle aspiration specimens.
AB  - The current FDA-approved standard of care for nonsmall cell lung cancer is
      Carboplastin/Taxol/Avastin based upon an impressive survival benefit; however,
      patients with squamous carcinoma (SQCC) cannot receive Avastin because of a 30%
      mortality rate due to fatal hemoptysis. In this study we evaluated the role of
      cytomorphology and immunohistochemistry in differentiating SQCC from
      adenocarcinoma (ADC) in lung FNA specimens. The case cohort included 53 FNA cases
      of nonsmall cell lung carcinoma with surgical pathology follow-up. All FNA
      specimens were reviewed independently by a panel of cytopathologists to
      differentiate between SQCC and ADC. The cell block material was available in 23
      cases (11 ADC and 12 SQCC) to perform immunohistochemical stains for TTF-1, CK7,
      CK20, P63, and CK5/6. On surgical resection, 35/53 (66%) cases were diagnosed as
      ADC and 18/53 (34%) as SQCC. The number of cases classified correctly on the
      basis of cytomorphology was 66% for ADC and 53% for SQCC (combined accuracy 60%).
      By immunohistochemical staining, 14/23 (61%) cases expressed TTF-1. Nine cases
      were TTF-1 negative; eight of the TTF-1 negative cases (89%) were SQCC. Twenty
      three cases expressed CK7 (87%); one ADC case (4%) showed focal CK20 positivity.
      Both P63 and CK5/6 expression was seen in 9/12 (75%) SQCC cases; none of the ADC
      cases showed this dual expression. Cytomorphology alone may not be able to
      stratify all cases of nonsmall cell lung carcinoma into ADC and SQCC in FNA
      specimens. The immune-panel of TTF-1, CK7, CK20, P63, and CK5/6 is useful in
      differentiating SQCC from ADC.

PMID- 19170170
TI  - Koilocytosis: correlations with high-risk HPV and its comparison on tissue
      sections and cytology, urothelial carcinoma.
AB  - The aim of this study were (1) To correlate koilocytosis with high risk
      HPV(HrHPV) DNA in urinary bladder carcinoma and (2) To compare detection of
      koilocytosis on tissue sections and urine cytology. Biopsy and cytologic
      specimens from 33 patients of urinary bladder carcinoma were analyzed. HPV DNA
      was detected by PCR on biopsy specimens using consensus primers MY09 and MY11.
      Koilocytosis was assessed both on tissue sections and urine cytology. HrHPV DNA
      was found in 14 of 33 bladder carcinoma. Koilocytosis was seen in tissue sections
      from 13 patients. Eleven of these were HrHPV DNA positive (positive predictive
      value 84.6%). Koilocytosis was seen in urine cytology in three patients. All
      three were positive for HrHPV DNA. To conclude koilocytosis is a good
      morphological marker for HrHPV DNA in the urothelium. Tissue sections are better
      than cytologic smears for detection of koilocytes.

PMID- 19170171
TI  - Conjunctival impression cytology in trachoma.
AB  - Trachoma is one of the leading causes of blindness and clinical examination
      remains the mainstay of diagnosis. However there is need to evaluate simple,
      inexpensive techniques which can be used for screening of trachoma in endemic
      regions. We report two cases where conjunctival impression cytology played a part
      in confirming the diagnosis of trachoma. We used a modified technique of
      obtaining conjunctival impressions, which not only met with better patient
      compliance and minimal ocular distress, but also provided better cellularity and
      morphology of cells for evaluation. The impression smears showed squamous
      metaplasia and loss of goblet cells. The cytoplasm of these cells had a hazy,
      moth eaten appearance and showed presence of intracytoplasmic inclusions. These
      basophilic inclusions were present singly and in clusters and were around 5 mum
      in diameter. A large number of these inclusions were present extracellularly as
      well. Conjunctival impression cytology is a simple procedure which needs to be
      evaluated for its potential to be used for screening trachoma in endemic areas.

PMID- 19170172
TI  - Discriminating hepatocellular carcinoma from metastatic carcinoma on fine-needle
      aspiration biopsy of the liver: the utility of immunocytochemical panel.
AB  - The cytomorphologic features of hepatocellular carcinoma (HCC) in fine-needle
      aspiration (FNA) biopsy are well described. However, correctly diagnosing HCC on
      cytologic features alone and differentiating it from metastatic adenocarcinoma
      (MAC) remains a challenge. Studies have recommended the use of various
      immunocytochemical (ICC) stains to aid in the diagnosis and distinction of these
      tumors with variable success rates. In this study, we evaluated a panel of seven
      ICC stains, HepPar1, glypican-3, polyclonal and monoclonal carcinoembryonic
      antigen (pCEA, mCEA), MOC-31, CK7, and CK20, in 42 FNA cases of HCC and 48 FNA
      cases of MAC. The aim was to identify the most sensitive and specific markers and
      the best panel for accurate diagnosis. Overall, 38 of 42 HCC and 44/48 MAC tumors
      were correctly identified by a panel of four markers, CK7, MOC-31, HepPar1, and
      glypica-3, with accuracy rate of 90.5 and 91.7%, respectively. In the HCC group,
      glypican-3 was most sensitive and detected in 34/42 (81%), whereas HepPar1 and
      pCEA were less sensitive and detected in 30/42 (71.4%) and 21/42 (50%),
      respectively. In the MAC group, MOC-31 was most sensitive and detected in 38/48
      (79.2%), followed by CK7 in 20/48 (41.7%). Stepwise logistic regression analysis
      showed that a panel of glypican-3, HepPar1, MOC-31, and CK7 is most helpful in
      diagnosing and accurately differentiating HCC from MAC on FNA biopsies of the
      liver. We conclude that a panel of HepPar1, glypican-3, MOC-31, and CK7
      accurately and statistically significantly differentiates these two malignancies
      (P < 0.05).

PMID- 19170173
TI  - Multinucleated giant cells in HIV-associated benign lymphoepithelial cyst-like
      lesions of the parotid gland on FNAC.
AB  - Benign lymphoepithelial cyst-like lesion (BLEL), a previously rare lesion of the
      parotid gland consisting of marked lymphoid hyperplasia with accompanying
      squamous-lined cysts, has been described in patients with the acquired immune
      deficiency syndrome (AIDS) or AIDS risk factors. Histologically, these cysts are
      lined by a squamous or cuboidal epithelium. The lumen contains a pale homogenous
      material with foamy macrophages and lymphocytes with the cyst wall having
      germinal centers and a dense infiltrate of lymphoid cells. On FNAC, the aspirates
      are mostly cystic with the presence of reactive lymphoid tissue, numerous
      histiocytes, and metaplastic cell clusters. Multinucleated giant cells (MGCs) are
      also rarely seen in such lesions. We report a case of HIV-associated BLEL with
      numerous large sized multinucleated giant cells.

PMID- 19170174
TI  - Primary small cell carcinoma of the lung initially presenting as a breast mass: a
      fine-needle aspiration diagnosis.
AB  - The incidence of metastases to the breast from extramammary sites is relatively
      low compared with the incidence of primary breast carcinoma. Primary sites which
      have a predilection for metastases to the breast include, in the order of
      decreasing frequency, malignant melanoma, lymphoma, lung carcinoma, ovarian
      carcinoma, and soft tissue sarcoma, followed by gastrointestinal and
      genitourinary primaries. Most lung primaries metastasizing to breast represent
      adenocarcinoma. Other types of lung carcinoma, including small cell carcinoma,
      are relatively rare. We report a case of lung small cell carcinoma metastasizing
      to the breast and initially presenting with a breast mass in a 50-year-old
      female. The tumor was first diagnosed on a fine-needle aspiration biopsy specimen
      (FNAB) from the breast lesion and subsequently supported by core biopsy. A
      discussion of the differential diagnoses to consider on FNAB follows. Because of
      the difference in treatment for primary small cell carcinoma of breast versus
      primary small cell carcinoma of the lung, as well as the difference in prognosis
      for both malignancies, determining the site of primary malignancy is crucial to
      adequate patient care.

PMID- 19170175
TI  - Myelomatous pleural effusion in a patient with plasmablastic myeloma: a case
      report.
AB  - Myelomatous pleural effusion is an unusual clinical condition associated with
      poor outcomes. We report a case with myelomatous pleural effusion upon the
      presentation of the disease. The patient had multiple risk factors for inferior
      prognosis of multiple myeloma, including old age, immunoglobulin D (IgD) isotype,
      high lactate dehydrogenase, C-reactive protein, beta2-microglogulin levels, and a
      high myeloma cell burden in the bone marrow. The myeloma cells in both bone
      marrow and pleural effusion had characteristic features of plasmablasts,
      including gigantic size, large and eccentrically placed nuclei, fine cytoplasm,
      and prominent nucleoli. Immunophenotypical analysis showed the plasmablastic
      cells in the pleural effusion were positive for surface CD38, cytoplasmic
      immunoglobulin, both kappa and lambda light chains but negative for surface CD19
      or CD79a. Our experience suggests that the diagnosis of myelomatous pleural
      effusion should be made with clinical alertness and careful cytological
      examination, preferably supplemented by immunophenotypical analysis.

PMID- 19170176
TI  - Sensitivity evaluation of fine-needle aspiration cytology in thyroid lesions.

PMID- 19170177
TI  - Glutathione peroxidase overexpression does not rescue impaired neurogenesis in
      the injured immature brain.
AB  - Traumatic brain injury (TBI) is a leading cause of disability among young
      children and is associated with long-term cognitive deficits. These clinical
      findings have prompted an investigation of the hippocampus in an experimental
      model of trauma to the developing brain at postnatal day (p21). Previous studies
      using this model have revealed a progressive loss of neurons in the hippocampus
      as brain-injured animals mature to young adulthood. Here we determined whether
      this hippocampal vulnerability is likewise reflected in altered neurogenesis and
      whether the antioxidant glutathione peroxidase (GPx) modulates neurogenesis
      during maturation of the injured immature brain. Male transgenic mice that
      overexpress GPx and wild-type littermates were subjected to controlled cortical
      impact or sham surgery on p21. At 2 weeks postinjury, the numbers of
      proliferating cells and immature neurons within the subgranular zone were
      measured by using Ki-67 and doublecortin, respectively. Bromodeoxyuridine (BrdU)
      was used to label dividing cells beginning 2 weeks postinjury. Survival (BrdU(+))
      and neuronal differentiation (BrdU(+)/NeuN(+)) were then measured 4 weeks later
      via confocal microscopy. Two-way ANOVA revealed no significant interaction
      between genotype and injury. Subsequent analysis of the individual effects of
      injury and genotype, however, showed a significant reduction in subgranular zone
      proliferation (Ki-67) at 2 weeks postinjury (P = 0.0003) and precursor cell
      survival (BrdU(+)) at 6 weeks postinjury (P = 0.016) and a trend toward reduced
      neuronal differentiation (BrdU(+)/NeuN(+)) at 6 weeks postinjury (P = 0.087).
      Overall, these data demonstrate that traumatic injury to the injured immature
      brain impairs neurogenesis during maturation and suggest that GPx cannot rescue
      this reduced neurogenesis.

PMID- 19170178
TI  - Ca2+- and thromboxane-dependent distribution of MaxiK channels in cultured
      astrocytes: from microtubules to the plasma membrane.
AB  - Large-conductance, voltage- and Ca2+-activated K+ channels (MaxiK) are broadly
      expressed ion channels minimally assembled by four pore-forming alpha-subunits
      (MaxiKalpha) and typically observed as plasma membrane proteins in various cell
      types. In murine astrocyte primary cultures, we show that MaxiKalpha is
      predominantly confined to the microtubule network. Distinct microtubule
      distribution of MaxiKalpha was visualized by three independent labeling
      approaches: (1) MaxiKalpha-specific antibodies, (2) expressed EGFP-labeled
      MaxiKalpha, and (3) fluorophore-conjugated iberiotoxin, a specific MaxiK pore
      blocker. This MaxiKalpha association with microtubules was further confirmed by
      in vitro His-tag pulldown, co-immunoprecipitation from brain lysates, and
      microtubule depolymerization experiments. Changes in intracellular Ca2+ elicited
      by general pharmacological agents, caffeine or thapsigargin, resulted in
      increased MaxiKalpha labeling at the plasma membrane. More notably, U46619, an
      analog of thromboxane A2 (TXA2), which triggers Ca2+-release pathways and whose
      levels increase during cerebral hemorrhage/trauma, also elicits a similar
      increase in MaxiKalpha surface labeling. Whole-cell patch clamp recordings of
      U46619-stimulated cells develop a approximately 3-fold increase in current
      amplitude indicating that TXA2 stimulation results in the recruitment of
      additional, functional MaxiK channels to the surface membrane. While microtubules
      are largely absent in mature astrocytes, immunohistochemistry results in brain
      slices show that cortical astrocytes in the newborn mouse (P1) exhibit a robust
      expression of microtubules that significantly colocalize with MaxiK. The results
      of this study provide the novel insight that suggests that Ca2+ released from
      intracellular stores may play a key role in regulating the traffic of
      intracellular, microtubule-associated MaxiK stores to the plasma membrane of
      developing murine astrocytes.

PMID- 19170180
TI  - Tripchlorolide protects neuronal cells from microglia-mediated beta-amyloid
      neurotoxicity through inhibiting NF-kappaB and JNK signaling.
AB  - Recent research has focused on soluble oligomeric assemblies of beta-amyloid
      peptides (Abeta) as the proximate cause of neuroinflammation, synaptic loss, and
      the eventual dementia associated with Alzheimer's disease (AD). In this study,
      tripchlorolide (T4), an extract of Tripterygium wilfordii Hook. F (TWHF), was
      studied as a novel agent to suppress neuroinflammatory process in microglial
      cells and to protect neuronal cells against microglia-mediated oligomeric Abeta
      toxicity. T4 significantly attenuated oligomeric Abeta(1-42)-induced release of
      inflammatory productions such as tumor necrosis factor-alpha, interleukin-1beta,
      nitric oxide (NO), and prostaglandin E2. It also downregulated the protein levels
      of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in
      microglial cells. Further molecular mechanism study demonstrated that T4
      inhibited the nuclear translocation of nuclear factor-kappaB (NF-kappaB) without
      affecting I-kappaBalpha phosphorylation. It repressed Abeta-induced JNK
      phosphorylation but not ERK or p38 MAPK. The inhibition of NF-kappaB and JNK by
      T4 is correlated with the suppression of inflammatory mediators in Abeta
      stimulated microglial cells. These results suggest that T4 protects neuronal
      cells by blocking inflammatory responses of microglial cells to oligomeric
      Abeta(1-42) and that T4 acts on the signaling of NF-kappaB and JNK, which are
      involved in the modulation of inflammatory response. Therefore, T4 may be an
      effective agent in modulating neuroinflammatory process in AD.

PMID- 19170179
TI  - Peripheral myelin protein 22 is regulated post-transcriptionally by miRNA-29a.
AB  - Peripheral myelin protein 22 (PMP22) is a dose-sensitive, disease-associated
      protein primarily expressed in myelinating Schwann cells. Either reduction or
      overproduction of PMP22 can result in hereditary neuropathy, suggesting a
      requirement for correct protein expression for peripheral nerve biology. PMP22 is
      post-transcriptionally regulated and the 3'untranslated region (3'UTR) of the
      gene exerts a negative effect on translation. MicroRNAs (miRNAs) are small
      regulatory molecules that function at a post-transcriptional level by targeting
      the 3'UTR in a reverse complementary manner. We used cultured Schwann cells to
      demonstrate that alterations in the miRNA biogenesis pathway affect PMP22 levels,
      and endogenous PMP22 is subjected to miRNA regulation. GW-body formation, the
      proposed cytoplasmic site for miRNA-mediated repression, and Dicer expression, an
      RNase III family ribonuclease involved in miRNA biogenesis, are co-regulated with
      the differentiation state of Schwann cells. Furthermore, the levels of Dicer
      inversely correlate with PMP22, while the inhibition of Dicer leads to elevated
      PMP22. Microarray analysis of actively proliferating and differentiated Schwann
      cells, in conjunction with bioinformatics programs, identified several candidate
      PMP22-targeting miRNAs. Here we demonstrate that miR-29a binds and inhibits PMP22
      reporter expression through a specific miRNA seed binding region. Over-expression
      of miR-29a enhances the association of PMP22 RNA with Argonaute 2, a protein
      involved in miRNA function, and reduces the steady-state levels of PMP22. In
      contrast, inhibition of endogenous miR-29a relieves the miRNA-mediated repression
      of PMP22. Correlation analyses of miR-29 and PMP22 in sciatic nerves reveal an
      inverse relationship, both developmentally and in post-crush injury. These
      results identify PMP22 as a target of miRNAs and suggest that myelin gene
      expression by Schwann cells is regulated by miRNAs.

PMID- 19170181
TI  - Endothelial NOS-deficient mice reveal dual roles for nitric oxide during
      experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is a demyelinating autoimmune disease characterized by
      infiltration of T cells into the central nervous system (CNS) after compromise of
      the blood-brain barrier. A model used to mimic the disease in mice is
      experimental autoimmune encephalomyelitis (EAE). In this report, we examine the
      clinical and histopathological course of EAE in eNOS-deficient (eNOS-/-) mice to
      determine the role of nitric oxide (NO) derived from this enzyme in the disease
      progression. We find that eNOS-/- mice exhibit a delayed onset of EAE that
      correlates with delayed BBB breakdown, thus suggesting that NO production by eNOS
      underlies the T cell infiltration into the CNS. However, the eNOS-/- mice also
      eventually exhibit more severe EAE and delayed recovery, indicating that NO
      undertakes dual roles in MS/EAE, one proinflammatory that triggers disease onset,
      and the other neuroprotective that promotes recovery from disease exacerbation
      events.

PMID- 19170182
TI  - GDNF-enhanced axonal regeneration and myelination following spinal cord injury is
      mediated by primary effects on neurons.
AB  - We previously demonstrated that coadministration of glial cell line-derived
      neurotrophic factor (GDNF) with grafts of Schwann cells (SCs) enhanced axonal
      regeneration and remyelination following spinal cord injury (SCI). However, the
      cellular target through which GDNF mediates such actions was unclear. Here, we
      report that GDNF enhanced both the number and caliber of regenerated axons in
      vivo and increased neurite outgrowth of dorsal root ganglion neurons (DRGN) in
      vitro, suggesting that GDNF has a direct effect on neurons. In SC-DRGN coculture,
      GDNF significantly increased the number of myelin sheaths produced by SCs. GDNF
      treatment had no effect on the proliferation of isolated SCs but enhanced the
      proliferation of SCs already in contact with axons. GDNF increased the expression
      of the 140 kDa neural cell adhesion molecule (NCAM) in isolated SCs but not their
      expression of the adhesion molecule L1 or the secretion of the neurotrophins NGF,
      NT3, or BDNF. Overall, these results support the hypothesis that GDNF-enhanced
      axonal regeneration and SC myelination is mediated mainly through a direct effect
      of GDNF on neurons. They also suggest that the combination of GDNF administration
      and SC transplantation may represent an effective strategy to promote axonal
      regeneration and myelin formation after injury in the spinal cord.

PMID- 19170183
TI  - Conduction block and glial injury induced in developing central white matter by
      glycine, GABA, noradrenalin, or nicotine, studied in isolated neonatal rat optic
      nerve.
AB  - The damaging effects of excessive glutamate receptor activation have been
      highlighted recently during injury in developing central white matter. We have
      examined the effects of acute exposure to four other neurotransmitters that have
      known actions on white matter. Eighty minutes of Glycine or GABA-A receptor
      activation produced a significant fall in the compound action potential recorded
      from isolated post-natal day 10 rat optic nerve. This effect was largely reversed
      upon washout. Nicotinic acetylcholine receptor (nAChR) or adrenoreceptor
      activation with noradrenalin resulted in an approximately 35% block of the action
      potential that did not reverse during a 30-min washout period. While the effect
      of nAChR activation was blocked by a nAChR antagonist, the effect of noradrenalin
      was not ablated by alpha- or beta-adrenoreceptor blockers applied alone or in
      combination. In the absence of noradrenalin, co-perfusion with alpha- and beta
      adrenoreceptor blockers resulted in nonreversible nerve failure indicating that
      tonic adrenoreceptor activation is required for nerve viability, while
      overactivation of these receptors is also damaging. Nerves exposed to nAChR +
      adrenoreceptor activation showed no axon pathology but had extensive glial injury
      revealed by ultrastructural analysis. Oligodendroglia exhibited regions of
      membrane vacuolization while profound changes were evident in astrocytes and
      included the presence of swollen and expanded mitochondria, vacuolization, cell
      processes disintegration, and membrane breakdown. Blinded assessment revealed
      higher levels of astrocyte injury than oligodendroglial injury. The findings show
      that overactivation of neurotransmitter receptors other than those for glutamate
      can produce extensive injury to developing white matter, a phenomenon that may be
      clinically significant.

PMID- 19170184
TI  - Functional alpha 7-containing nicotinic receptors of NG2-expressing cells in the
      hippocampus.
AB  - In the postnatal central nervous system, glial cells expressing the chondroitin
      sulfate proteoglycan NG2 (NG2-cells) constitute a cell population exhibiting
      several properties of oligodendrocyte precursors such as the ability to
      proliferate. One particular feature of NG2-cells is that they express several
      glutamatergic and GABAergic ionotropic receptors activated by synaptic
      neurotransmitter release. Here, we used patch-clamp recordings, immunostaining,
      calcium imaging, and intracellular labeling to test for the presence of
      ionotropic nicotinic acetylcholine receptors (nAChRs) in NG2-cells identified in
      acute hippocampal slices of mice. We demonstrated that these cells express
      functional nAChRs during the second postnatal week, i.e., the period in which
      they become the most abundant proliferative cell type of CA1 stratum radiatum.
      Pharmacological experiments showed that NG2-cells express alpha 7-containing
      nAChRs. In particular, the powerful positive allosteric modulator of these
      receptors PNU-120596 induced a 20-fold increase of agonist-induced currents and
      revealed rises in intracellular calcium concentration upon agonist applications.
      In addition, nanomolar concentrations of nicotine, which did not induce any
      response in these cells, largely desensitized nAChR-mediated currents. These data
      indicate that the functional expression of Ca(2+)-permeable alpha 7-containing
      nAChRs in hippocampal slices is not restricted to neurons and that the receptors
      of NG2-cells can be desensitized by low concentrations of nicotine.

PMID- 19170185
TI  - Enriched environment fails to increase meningitis-induced neurogenesis and
      spatial memory in a mouse model of pneumococcal meningitis.
AB  - An increase in adult neurogenesis was observed after exposure to enriched
      environment (EE) and during reconvalescence from experimental pneumococcal
      meningitis. This study investigated neurogenesis and spatial learning performance
      5 weeks after bacterial meningitis and exposure to EE. C57BL/6 mice were infected
      by intracerebral injection of Streptococcus pneumoniae and treated with
      ceftriaxone for 5 days. Forty-eight hours after infection, one group (n = 22) was
      exposed to EE and the other group (n = 23) housed under standard conditions.
      Another set of mice was kept under either enriched (n = 16) or standard (n = 15)
      conditions without bacterial meningitis. Five weeks later, the Morris water maze
      was performed, and neurogenesis was evaluated by means of immunohistochemistry.
      Mice housed in EE without prior bacterial infection displayed both increased
      neurogenesis and improved water maze performance in comparison with uninfected
      control animals. Bacterial meningitis stimulated neurogenesis in the granular
      cell layer of the dentate gyrus: with standard housing conditions, we observed a
      higher density of BrdU-immunolabeled and TUC-4-expressing cells 5 weeks after
      induction of bacterial meningitis than in the noninfected control group. EE did
      not further increase progenitor cell proliferation and neuronal differentiation
      in the subgranular cell layer of the dentate gyrus after bacterial meningitis in
      comparison with infected mice housed under standard conditions. Moreover, the
      Morris water maze showed no significant differences between survivors of
      meningitis exposed to EE and animals kept in standard housing. In summary,
      exposure to EE after pneumococcal meningitis did not further increase meningitis
      induced neurogenesis or improve spatial learning.

PMID- 19170186
TI  - Deprivation-induced dendritic shrinkage might be oppositely affected by the
      expression of wild-type and mutated human amyloid precursor protein.
AB  - The physiological role of the amyloid precursor protein (APP) and its proteolytic
      fragments in the brain is associated with neuronal survival, neurite outgrowth,
      synaptic formation, and neuronal plasticity. However, malregulation of APP
      processing leads to disordered balance of fragments, which may results in
      opposite, degenerative neuronal effects. In the present study, we analyzed in
      vivo effects of the expression of wild-type or mutated human APP on afferent
      deprivation-induced changes of dendritic morphology. After vibrissectomy,
      expression of wild-type human APP prevented diameter shrinkage of dendritic
      segments as well as dendritic rarefaction of apical arbors. In contrast, mutant
      human APP expression exacerbated degenerative changes of deprived barrel neurons.
      Degradation of apical arbors was especially pronounced. Results demonstrate for
      the first time opposite effects of the expression of wild-type and mutated human
      APP on deprivation-induced dendritic restructuring in vivo.

PMID- 19170187
TI  - Neuropathy-induced apoptosis: protective effect of physostigmine.
AB  - Traumatic, infectious, metabolic, and chemical noxa to the nervous system are the
      etiology of a crippling disease generally termed neuropathy. Motor disorders,
      altered sensibility, and pain are the pathognomonic traits. Cellular alterations
      induced by this chronic pathology include mitochondrial dysfunctions that lead to
      the activation of the apoptotic cascade. Energy imbalance can compromise the
      maintenance of mitochondrial membrane potential, furthering the release of
      cytochrome C and the subsequent cleavage and activation of caspases. Chronic
      constriction injury (CCI) of the rat sciatic nerve is a neuropathy model able to
      induce a strong mitochondrial impairment with a consequent apoptotic induction.
      In this model, the acetylcholinesterase inhibitor physostigmine is administered
      at 0.125 mg/kg i.p. (twice per day) starting from the operation and for 15 days
      after. The cholinergic activation reduces cytosolic levels of cytochrome C,
      suggesting an improved stability of the mitochondrial membrane, and the
      expression level of the active caspase 3 fragments (19, 16 kDa) is reduced
      significantly with respect to saline treatment. Accordingly, physostigmine
      impairs caspase 3 protease activity. In fact, the target of the activated caspase
      3, the 89-kDa PARP fragment, is significantly less expressed in the ligated nerve
      of physostigmine-treated rats, reaching levels that are comparable to those in
      the contralateral unligated nerve. Finally, this natural acetylcholinesterase
      inhibitor reduces DNA fragmentation both in the proximal and in the distal parts
      of the nerve. This protection correlates with the induction of XIAP. Therefore,
      apoptosis, central to tissue degeneration, is prevented by repeated physostigmine
      treatment of CCI animals.

PMID- 19170188
TI  - The SNARE protein SNAP-29 interacts with the GTPase Rab3A: Implications for
      membrane trafficking in myelinating glia.
AB  - During myelin formation, vast amounts of specialized membrane proteins and lipids
      are trafficked toward the growing sheath in cell surface-directed transport
      vesicles. Soluble N-ethylmaleimide-sensitive factor (NSF) attachment proteins
      (SNAPs) are important components of molecular complexes required for membrane
      fusion. We have analyzed the expression profile and molecular interactions of
      SNAP-29 in the nervous system. In addition to its known enrichment in neuronal
      synapses, SNAP-29 is abundant in oligodendrocytes during myelination and in
      noncompact myelin of the peripheral nervous system. By yeast two-hybrid screen
      and coimmunoprecipitation, we found that the GTPases Rab3A, Rab24, and septin 4
      bind to the N-terminal domain of SNAP-29. The interaction with Rab24 or septin 4
      was GTP independent. In contrast, interaction between SNAP-29 and Rab3A was GTP
      dependent, and colocalization was extensive both in synapses and in myelinating
      glia. In HEK293 cells, cytoplasmic SNAP-29 pools were redistributed upon
      coexpression with Rab3A, and surface-directed trafficking of myelin proteolipid
      protein was enhanced by overexpression of SNAP-29 and Rab3A. Interestingly, the
      abundance of SNAP-29 in sciatic nerves was increased during remyelination and in
      a rat model of Charcot-Marie-Tooth disease, two pathological situations with
      increased myelin membrane biogenesis. We suggest that Rab3A may regulate SNAP-29
      mediated membrane fusion during myelination.

PMID- 19170189
TI  - Allied health care in Parkinson's disease: referral, consultation, and
      professional expertise.
AB  - There is evidence for the efficacy of allied health care in Parkinson's disease
      (PD). However, barriers exist that hamper implementation of evidence into daily
      practice. We conducted a survey to investigate: (1) to what extent PD patients
      currently utilize allied health care for relevant problems in the core areas of
      allied health care and (2) the level of PD-specific expertise among allied health
      professionals. Questionnaires were sent to 260 patients and 297 allied health
      professionals. Referral rates were 63% for physical therapy, 9% for occupational
      therapy, and 14% for speech therapy. PD patients with problems that can
      potentially be alleviated by input from allied health professionals are often not
      being referred. Furthermore, most patients were treated by allied health
      professionals who lacked PD-specific expertise. Current referral to and delivery
      of allied health care in PD are suboptimal. Evidence-based guidelines for allied
      health care in PD and active implementation of these guidelines are needed.

PMID- 19170190
TI  - Microsubthalamotomy effect at day 3: screening for determinants.
AB  - A microsubthalamotomy (mSTN) effect has been frequently reported after
      implantation that improves Parkinson's motor disability. It is usually believed
      that mSTN effect reflects the post-traumatic tissue reaction within the STN.
      However, it has never, to our knowledge, been reported whether pre and
      intraoperative factors could predict this mSTN effect. Preoperative clinical
      characteristics, that is, age, disease duration, Mattis Dementia Rating Scale
      score, levodopa responsiveness, severity of motor fluctuations and dyskinesia,
      and intraoperative parameters, that is, the number of tracks, distance of typical
      STN neuronal activity recorded along all microelectrodes, and along the
      definitive electrodes, were assessed in 40 consecutive PD patients submitted for
      STN stimulation. Multiple stepwise regression analysis showed that only the
      number of tracks used for microelectrodes recordings was predictor of the
      contralateral mSTN effect (F (4,73) = 1.83, P = 0.02). This result suggests that
      the contralateral mSTN depends on the tissue changes along the entirety of
      surgical trajectories affecting both STN and its adjacent structures.

PMID- 19170191
TI  - Effects of active and passive smoking on disease course of Crohn's disease and
      ulcerative colitis.
AB  - BACKGROUND: Smoking is a remarkable risk factor for inflammatory bowel disease
      (IBD), aggravating Crohn's disease (CD) while having beneficial effects on
      ulcerative colitis (UC). We studied the effects of active and passive smoking in
      Dutch IBD patients. METHODS: A questionnaire focusing on cigarette smoke exposure
      was sent to 820 IBD patients. Returned questionnaires were incorporated into a
      retrospective chart review, containing details about disease behavior and
      received therapy. RESULTS: In all, 675 IBD patients (380 [56%] CD and 295 [44%]
      UC) responded. At diagnosis there were 52% smokers in CD, 41% in the general
      population, and 28% in UC. The number of present smokers in CD is lower than in
      the general population (26% versus 35%). No detrimental effects of active smoking
      on CD were observed, but passive smokers needed immunosuppressants and infliximab
      more frequently than nonpassive smokers. Active smoking had beneficial effects on
      UC, indicated by reduced rates of colectomy, primary sclerosing cholangitis, and
      backwash-ileitis in active smokers compared to never smokers, and higher daily
      cigarette dose correlated with less extensive colitis and a lower need for
      therapy. Furthermore, smoking cessation after diagnosis was detrimental for UC
      patients, indicated by increased needs for steroids and hospitalizations for
      patients that stopped smoking after compared to before the diagnosis.
      CONCLUSIONS: Active smoking is a risk factor for CD, but does not affect the
      outcome; passive smoking is detrimental for the outcome of CD patients. In UC,
      active smoking shows dose-dependent beneficial effects. Our data suggest that
      passive smoking is a novel risk factor for CD.

PMID- 19170192
TI  - Surgical treatment of complex enterocutaneous fistulas in IBD patients using
      human acellular dermal matrix.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) patients represent a high-risk group
      for enterocutaneous fistula (ECF) formation, related to both their disease
      process and the need for multiple surgeries. Often the abdominal wall is
      significantly involved with the ECF and requires partial resection. The use of
      synthetic prosthetic material to reconstruct the abdominal wall after ECF surgery
      is associated with increased risk of infection and recurrent fistulas. Herein we
      report the use human acellular dermal matrix (hADM) in the surgical treatment and
      reconstruction of the abdominal wall in 11 consecutive IBD patients with complex
      and medically refractory ECF. METHODS: After resection of the involved bowel
      segment and the overlying abdominal wall, a single sheet of hADM was used to
      reconstruct the defect. Pre- and perioperative risk factors were reviewed and
      patients were followed prospectively for a year (360 +/- 118 days). RESULTS:
      Operative mortality was nil. Three patients (27%) developed subcutaneous seroma
      and there were 2 cases (18%) of superficial wound infection, all of which
      resolved with conservative management. The mean length of hospital stay was 13.5
      (+/-7.2) days and all patients were tolerating an oral diet at the time of
      dismissal. There were no recurrences. One patient with Crohn's disease developed
      a new ECF from a separate bowel site on postoperative day 145, which was treated
      with the same surgical approach. No further complications have occurred.
      CONCLUSIONS: Our results indicate that in a high-risk IBD patient population with
      multiple perioperative risk factors the use of hADM during ECF takedown is an
      effective and well-tolerated treatment option.

PMID- 19170193
TI  - Peripheral neuropathy with infliximab therapy in inflammatory bowel disease.

PMID- 19170194
TI  - Sonographic substantia nigra hypoechogenicity in polyneuropathy and restless legs
      syndrome.
AB  - Substantia nigra (SN) hypoechogenicity assessed by transcranial B-mode sonography
      (TCS) is typical for idiopathic restless legs syndrome (RLS). Here, we
      investigated whether SN hypoechogenicity may differentiate between polyneuropathy
      (PNP) patients with and without RLS. Seventy-five patients with PNP, 65 healthy
      controls, and 75 patients with idiopathic RLS were investigated. A total of 41.2%
      patients with PNP additionally suffered from RLS. A total of 44.1% patients with
      PNP, 10.2% of healthy controls, and 91.2% of patients with idiopathic RLS
      exhibited SN hypoechogenicity. SN echogenicity did not differ significantly
      between PNP patients with and without RLS. Thus, TCS seems not suitable for the
      diagnosis of RLS in patients with PNP.

PMID- 19170195
TI  - Apoptosis induction by sulfur-containing compounds in malignant and nonmalignant
      human cells.
AB  - Plants have traditionally represented a main source for the discovery of many
      biologically active substances with therapeutic values. Sulfur-containing
      compounds exhibit pleiotropic biological effects supporting their potential use
      in multitargeted cancer prevention and treatment. As potential anti-cancer
      agents, they have been shown to inhibit or retard the growth of various cancer
      cells in culture and implanted tumors in vivo. The compounds significantly
      inhibit experimental tumorigenesis in a wide range of animal models. A critical
      and well-elucidated cellular mechanism involved in the anticancer activities of
      sulfur-containing compounds is the induction of apoptosis through the fine-tuning
      of orchestrated intracellular signal transduction. This review summarizes the
      established proapoptotic activities of sulfur-containing compounds in malignant
      and nonmalignant cells with a special focus on their molecular mechanisms. The
      potential toxicological implications of proapoptotic effects on normal cells will
      also be discussed.

PMID- 19170196
TI  - Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China.
AB  - The high incidence of lung cancer in Xuanwei County, China has been attributed to
      exposure to indoor smoky coal emissions that contain polycyclic aromatic
      hydrocarbons (PAHs). The inflammatory response induced by coal smoke components
      may promote lung tumor development. We studied the association between single
      nucleotide polymorphisms (SNPs) in genes involved in innate immunity and lung
      cancer risk in a population-based case-control study (122 cases and 122 controls)
      in Xuanwei. A total of 1,360 tag SNPs in 149 gene regions were included in the
      analysis. FCER2 rs7249320 was the most significant SNP (OR: 0.30; 95% CI: 0.16
      0.55; P: 0.0001; false discovery rate value, 0.13) for variant carriers. The gene
      regions ALOX12B/ALOX15B and KLK2 were associated with increased lung cancer risk
      globally (false discovery rate value <0.15). In addition, there were positive
      interactions between KLK15 rs3745523 and smoky coal use (OR: 9.40; P-interaction
      = 0.07) and between FCER2 rs7249320 and KLK2 rs2739476 (OR: 10.77; P-interaction
      = 0.003). Our results suggest that genetic polymorphisms in innate immunity genes
      may play a role in the genesis of lung cancer caused by PAH-containing coal
      smoke. Integrin/receptor and complement pathways as well as IgE regulation are
      particularly noteworthy.

PMID- 19170197
TI  - Treatment of the symptoms of Huntington's disease: preliminary results comparing
      aripiprazole and tetrabenazine.
AB  - Aripiprazole (AP), a dopamine (DA) D(2) receptor partial agonist, has recently
      been used to reduce schizophrenic symptoms, while tetrabenazine (TBZ), a DA
      depletor, has been used to treat hyperkinesias in Huntington's disease (HD). The
      aim of this study is to define the role of AP on chorea, motor performance, and
      functional disability, and to compare the effects of AP vs. TBZ in a small study
      of six patients with HD. Both AP and TBZ increased the Unified Huntington's
      Disease Rating Scale (UHDRS) chorea score in a similar way. However, AP caused
      less sedation and sleepiness than TBZ and was better tolerated by the patients on
      the trial. Moreover, AP showed a slight but not significant improvement of
      depression in the patients as compared to TBZ. A larger group of patients and a
      longer period of observation are an important prerequisite for further
      evaluations of AP's therapeutic use.

PMID- 19170198
TI  - The management of tics.
AB  - A tic is a stereotyped repetitive involuntary movement or sound, frequently
      preceded by premonitory sensations or urges. Most tic disorders are genetic or
      idiopathic in nature, possibly due to a developmental failure of inhibitory
      function within frontal-subcortical circuits modulating volitional movements.
      Currently available oral medications can reduce the severity of tics, but rarely
      eliminate them. Botulinum toxin injections can be effective if there are a few
      particularly disabling motor tics. Deep brain stimulation has been reported to be
      an effective treatment for the most severe cases, but remains unproven. A
      comprehensive evaluation accounting for secondary causes, psychosocial factors,
      and comorbid neuropsychiatric conditions is essential to successful treatment of
      tic disorders.

PMID- 19170200
TI  - A Y-chromosomal comparison of the Madjars (Kazakhstan) and the Magyars (Hungary).
AB  - The Madjars are a previously unstudied population from Kazakhstan who practice a
      form of local exogamy in which wives are brought in from neighboring tribes, but
      husbands are not, so the paternal lineages remain genetically isolated within the
      population. Their name bears a striking resemblance to the Magyars who have
      inhabited Hungary for over a millennium, but whose previous history is poorly
      understood. We have now carried out a genetic analysis of the population
      structure and relationships of the Madjars, and in particular have sought to test
      whether or not they show a genetic link with the Magyars. We concentrated on
      paternal lineages because of their isolation within the Madjars and sampled males
      representing all extant male lineages unrelated for more than eight generations
      (n = 45) in the Torgay area of Kazakhstan. The Madjars show evidence of extensive
      genetic drift, with 24/45 carrying the same 12-STR haplotype within haplogroup G.
      Genetic distances based on haplogroup frequencies were used to compare the
      Madjars with 37 other populations and showed that they were closest to the
      Hungarian population rather than their geographical neighbors. Although this
      finding could result from chance, it is striking and suggests that there could
      have been genetic contact between the ancestors of the Madjars and Magyars, and
      thus that modern Hungarians may trace their ancestry to Central Asia, instead of
      the Eastern Uralic region as previously thought.

PMID- 19170199
TI  - Cardiac and noncardiac fibrotic reactions caused by ergot-and nonergot-derived
      dopamine agonists.
AB  - There is growing evidence that the ergot-derived dopamine agonists cabergoline
      and pergolide can cause fibrotic cardiac valvulopathy. Data on other fibrotic
      reactions and nonergot-derived dopamine agonists are sparse. Aim of this study
      was to investigate whether there are signals that dopamine agonists are related
      to cardiac and other fibrotic reactions. We identified all reports of fibrotic
      reactions at the heart, lung, and retroperitoneal space associated with dopamine
      agonists within the US Adverse Event Reporting System database.
      Disproportionality analyses were used to calculate adjusted reporting odds ratios
      (RORs). For ergot-derived dopamine agonists (bromocriptine, cabergoline,
      pergolide), the RORs of all reactions under study were increased, whereas no such
      increases were observed for nonergot-derived drugs (apomorphine, pramipexole,
      ropinirole, rotigotine). Fibrotic reactions due to ergot-derived dopamine
      agonists may not be limited to heart valves. For nonergot-derived dopamine
      agonists, no drug safety signals were evident.

PMID- 19170201
TI  - Manual digital pressures during knuckle-walking in chimpanzees (Pan troglodytes).
AB  - Considerable attention has been given to hand morphology and function associated
      with knuckle-walking in the African apes because of the implications they have
      for the evolution of bipedalism in early hominins. Knuckle-walking is associated
      with a unique suite of musculoskeletal features of the wrist and hand, and
      numerous studies have hypothesized that these anatomical features are associated
      with the dynamics of load distribution across the digits during knuckle-walking.
      We collected dynamic digital pressures on two chimpanzees during terrestrial and
      simulated arboreal locomotion. Comparisons were made across substrates, limb
      positions, hand positions, and age categories. Peak digital pressures were
      similar on the pole and on the ground but were distributed differently across the
      digits on each substrate. In young animals, pressure was equally high on digits 2
      4 on the ground but higher on digits 3 and 4 on the pole. Older animals
      experience higher pressures on digits 2 and 3 on the ground. Hand posture (palm
      in vs. palm-back) influenced the distribution and timing of peak pressures. Age
      related increases in body mass also result in higher overall pressures and
      increased variation across the digital row. In chimpanzees, digit 5 typically
      bears relatively little load regardless of hand position or substrate. These are
      the first quantitative data on digital pressures during knuckle-walking in
      hominoids, and they afford the opportunity to develop hypotheses about variation
      among hominoids and biomechanical models of wrist and forearm loading.

PMID- 19170203
TI  - Technical note: virtual reconstruction of a fragmentary clavicle.
AB  - We report a procedure for the virtual reconstruction of incomplete human bones
      applicable to skeletal remains from archaeological excavations or to
      reconstructive and prosthetic surgery. To test the procedure, we reconstructed a
      fragmented left clavicle on the basis of the contralateral clavicle. The
      procedure involved 3-D laser scanner acquisition of the left clavicle (complete
      but broken into two parts), the same manually reconstructed bone, and the intact
      right clavicle, which was mirror-imaged and used as a reference for the
      reconstruction of the whole left clavicle. Because it was not possible to
      recognize homologous anatomical landmarks, on the two reference models (a mirror
      image copy of the right clavicle and the main fragment of the left), we
      identified three grids with an increasing number of corresponding landmarks,
      which constituted the framework of the deformation process. The three
      reconstructed digital models of the clavicle closely approximated the model of
      the original clavicle. They also showed that an increasing number of landmarks
      did not significantly improve the reconstructed model.

PMID- 19170204
TI  - Intratumoral interferon regulatory factor (IRF)-1 but not IRF-2 is of relevance
      in predicting patient outcome in ovarian cancer.
AB  - IRF-1 and IRF-2 expression was determined by real-time PCR in 138 ovarian cancer
      samples and 30 healthy ovarian biopsies and was correlated with the expression of
      other relevant immunologic parameters and common clinicopathologic variables.
      Regulation of IRF-1 and IRF-2 was evaluated by cytokine treatment of various
      ovarian cancer cell lines, human peritoneal mesothelial cells and ovarian surface
      epithelium. IRF-1 but not IRF-2 was constitutively over-expressed in 5 of 7
      ovarian cancer cell lines. Both IRFs were inducible with IFN-gamma and to a
      lesser extent with IL-1 or TNF-alpha, but not with IL-6. Epidermal growth factor
      (EGF) treatment down-regulated both IRFs. In ovarian cancer samples only IRF-1,
      but not IRF-2 mRNA, was up-regulated when compared with healthy ovarian tissue.
      IRF-1 but not IRF-2 expression was significantly associated with interferon (IFN)
      gamma and forkhead box P3 (FoxP3). In univariate survival analysis, strong
      expression of IRF-1 and IRF-2 predicted improved disease-free survival (DFS) and
      overall survival (OS). In Cox regression analyses, IRF-1 retained independent
      prognostic significance for DFS and OS and IFN-gamma for OS. In contrast to other
      solid tumors, IRF-2 expression cannot be regarded as a classic oncoprotein
      associated with poor prognosis in ovarian cancer. Of the immunologic parameters
      investigated, intratumoral IRF-1 expression is the most powerful independent
      predictor of a favorable clinical outcome.

PMID- 19170205
TI  - Investigation on the presence of polyomavirus, herpesvirus, and papillomavirus
      sequences in colorectal neoplasms and their association with cancer.

PMID- 19170206
TI  - Mutation in the DNA-binding domain of the EWS-Oct-4 oncogene results in dominant
      negative activity that interferes with EWS-Oct-4-mediated transactivation.
AB  - The EWS-Oct-4 protein is a chimeric molecule in which the amino terminal domain
      (NTD) of the EWS becomes fused to the carboxy terminal domain (CTD) of the Oct-4
      transcription factor. It was identified in human bone and soft-tissue tumors
      associated with t(6;22)(p21;q12). Using in vitro and in vivo systems, we found
      that the EWS-Oct-4 protein self-associates. The major domains required for self
      association mapped to the EWS NTD (amino acids 70-163) and the POU DNA-binding
      domain. EWS-Oct-4 protein also associated with EWS-Oct-4 (V351P), which contains
      a mutation in the POU DNA-binding domain. Using electrophoretic mobility shift
      assays, we found that the EWS-Oct-4 (V351P) mutant interfered with wild-type EWS
      Oct-4 DNA-binding activity. In addition, we found that EWS-Oct-4-mediated
      transcriptional activation was inhibited by EWS-Oct-4 (V351P) protein in vivo.
      Thus, this mutation in the POU DNA-binding domain results in a dominant negative
      protein. These findings suggest that the biological functions of the EWS-Oct-4
      oncogene can be modulated by the dominant negative mutant EWS-Oct-4 (V351P).

PMID- 19170207
TI  - DNA methylation status is inversely correlated with green tea intake and physical
      activity in gastric cancer patients.
AB  - Epigenetic silencing of genes by aberrant DNA methylation is recognized as a
      crucial component of the mechanism underlying tumorigenesis. However, the
      relationship between DNA methylation and the past lifestyle in cancer patients
      remains largely unknown. We examined the methylation statuses of 6 tumor-related
      genes, CDX2 (homeobox transcription factor), BMP-2 (bone morphogenetic protein
      2), p16 (INK4A), CACNA2D3 (calcium channel-related), GATA-5 (transcription
      factor) and ER (estrogen receptor), in 106 primary gastric carcinomas by
      methylation-specific PCR and compared them with the past lifestyles of the
      patients. The methylation frequencies of the genes were 23.6, 21.7, 9.4, 32.4,
      40.8 and 59.1%, respectively. Significant association was found between a
      decreased intake of green tea and methylation of CDX2 and BMP-2. More physical
      activity was correlated with a lower methylation frequency of CACNA2D3. Of these
      6 genes, the methylation statuses of CDX2, BMP-2 and p16 revealed a significant
      interrelationship and those of CACNA2D3, GATA-5 and ER did likewise. Thus, some
      epidemiological factors, such as green tea intake, could be important as to
      determination of the methylation statuses of selected genes and may influence the
      development of cancer, including that of the stomach.

PMID- 19170209
TI  - Linkage disequilibrium patterns and genetic structure of Amerindian and non
      Amerindian Brazilian populations revealed by long-range X-STR markers.
AB  - The extent of X-chromosome linkage disequilibrium (LD) was studied in a southern
      Brazilian population, and in a pool of samples from Amerindian populations. For
      this purpose, 11 microsatellites, located mostly in a Xq region comprising
      approximately 86 Mb was investigated. The lower Amerindian gene diversity
      associated with significant differences between the populations studied indicated
      population structure as the main cause for the higher LD values in the Amerindian
      pool. On the other hand, the LD levels of the non-Amerindian Brazilian sample,
      although less extensive than that of the Amerindians, were probably determined by
      admixture events. Our results indicated that different demographic histories have
      significant effects on LD levels of human populations, and provide a first
      approach to the X-chromosome ancestry of Amerindian and non-Amerindian Brazilian
      populations, being valuable for future studies involving mapping and population
      genetic studies.

PMID- 19170210
TI  - Asymmetry of the os pubis: implications for the Suchey-Brooks method.
AB  - Studies of skeletal development frequently document populational incidences of
      bilateral asymmetry. Degenerative morphological skeletal changes, attributed to
      age related and irregular ossification, may also progress asymmetrically, either
      as the result of asymmetric biomechanical factors expressed over the lifespan,
      asymmetric expression of physiological processes, or progressive magnification of
      asymmetry acquired previously during development. This study illustrates the
      effects of bilateral asymmetry on age at death estimates obtained from human
      skeletal remains. The Suchey-Brooks method, which uses the pubic symphyseal face
      for age estimation (Katz and Suchey, Am J Phys Anthropol 69 1986 427-435), was
      selected for the study based on its widespread use. Asymmetry in the Suchey
      Brooks symphyseal age phases was found in over 60% of a sample composed of 20th
      century White male individuals from 18 to 86 years of age (N = 130). However,
      results suggest that the presence of asymmetry does not compromise the accuracy
      of the Suchey-Brooks method if the morphologically older symphyseal face of an
      asymmetric individual is used to estimate age at death. In addition, weak
      directional asymmetry and a correlation between age and asymmetry were found.
      This suggests that a comparison of asymmetry in this area with that in other
      skeletal areas, where the factors originating and influencing asymmetry are
      better understood, may be useful in better understanding the biological processes
      which underlie the age markers used in the Suchey-Brooks method.

PMID- 19170211
TI  - Brief communication: high-resolution assessment of the dental developmental
      pattern and characterization of tooth tissue proportions in the late Upper
      Paleolithic child from La Madeleine, France.
AB  - Affinities and differences in dental maturational patterns between modern humans
      and Neanderthals remain a matter of discussion. In particular, deciduous teeth
      are rare for Late Pleistocene humans, and few entire sequences have been detailed
      for their developmental status. Here, we report the results from the 3D virtual
      reconstruction and structural analysis of the deciduous lower dentition (nine
      teeth in situ) of the child from La Madeleine (LM4), France, the first Upper
      Paleolithic specimen detailed so far by means of high-resolution microtomography
      (microCT). With respect to the modern dental developmental standards, age at
      death of this individual is now more likely estimated within the interval 3-4
      years. LM4 lacks the slight discrepancy between a proportionally advanced stage
      of mineralization of the deciduous first molar and a relatively delayed
      maturational level of the incisors, which is found in Neanderthals (Bayle et al.:
      J Hum Evol 56 [2009] 66-75). By using a Bayesian approach, we calculated the
      probability that its maturational sequence is found within the extant human
      variation as represented by a tomographic (CT) reference sample of 45 children
      scored according to the same protocol (Liversidge and Molleson: Am J Phys
      Anthropol 123 [2004] 172-180). Results show that the specific sequence of this
      Magdalenian individual is found three times in the comparative sample included in
      this study. LM4 absolute tooth size and relative dental tissue proportions are
      close to the modern human figures (characterized by proportionally reduced
      dentine volumes) and lie systematically below the values shown by the Neanderthal
      child from Roc de Marsal, France (OIS 5a).

PMID- 19170208
TI  - Use of oral contraceptives, intrauterine devices and tubal sterilization and
      cancer risk in a large prospective study, from 1996 to 2006.
AB  - The association of contraceptive methods, including oral contraceptives (OC),
      intrauterine devices (IUD) and tubal sterilization (TS), with overall and site
      specific cancer were prospectively investigated in a cohort of 66,661 Chinese
      women in Shanghai, 76.7% of whom used contraception. During a median follow-up
      time of 7.5 years, 2,250 women were diagnosed with cancer. Ever-use of any
      contraceptive method was not associated with overall cancer risk [adjusted hazard
      ratio (HR(adj)) = 1.02, 95% CI, 0.92-1.12]. Use of any contraceptive method was
      associated with increased risk of rectal cancer (HR(adj) = 1.68, 95% CI, 1.08
      2.62) and reduced risk of thyroid cancer (HR(adj) = 0.63, 95% CI, 0.38-1.04).
      Risk of gallbladder cancer increased with ever use of OC (HR(adj) = 2.38, 95% CI,
      1.26-4.49). IUD use was associated with a possible reduced risk of thyroid cancer
      (HR(adj) = 0.64, 95% CI, 0.38-1.07). Longer duration of IUD use decreased risk
      for breast, thyroid and lung cancers. Ever having a TS was associated with
      increased uterine body cancer (HR(adj) = 2.50, 95% CI, 1.47-4.25) and decreased
      risk of stomach cancer (HR(adj) = 0.59, 95% CI, 0.39-0.91). We did not find any
      contraceptive method to be related to the risk of ovarian cancer but the analyses
      were based on few events. Although chance findings are a likely explanation for
      some of the associations found in our study, these findings suggest that various
      contraceptive methods or reproductive patterns may play a role in the etiology of
      cancer.

PMID- 19170212
TI  - Brief communication: histology and micro CT as methods for assessment of facial
      suture patency.
AB  - The extent of fusion in facial sutures has implications for topics ranging from
      biomechanics to phylogeny reconstruction. An unfortunate limitation of studying
      sutural fusion in skeletal specimens is that it is difficult to assess whether
      apparently patent sutures are in fact fused internally. Both histology and
      microcomputed tomography (CT) are potential tools for solving this, but
      relatively few studies have attempted to discern the limits of micro CT for
      visualization of microanatomical structures. We examined microanatomical aspects
      of facial sutures in adult cadaveric samples from captive bushbabies.
      Premaxillary and nasopremaxillary sutures were examined in serially sectioned
      snouts of four greater bushbabies (Otolemur garnettii) and four lesser bushbabies
      (Galago moholi). Sections containing sutures with osseous bridging were rated as
      "fused," and the presence or absence of grooves on the external side was
      recorded. One bushbaby was studied using micro CT prior to physical sectioning.
      O. garnettii and two of the G. moholi show multiple foci of fusion. Histological
      examination confirmed that sutural fusion is limited to the internal surface in
      numerous sections, resulting in an external notch. Such points of internal fusion
      could be clearly visualized in raw CT slices. The presence of such notches
      suggests that external examination can underestimate the degree of suture fusion.
      Thus, microanatomical evidence may be needed to fully assess biomechanical
      correlates and phylogenetic interpretations based on fusion of facial sutures.
      Our results also indicate micro CT may be a useful tool to obtain this evidence.

PMID- 19170213
TI  - Paleoepidemiological patterns of interpersonal aggression in a prehistoric
      central California population from CA-ALA-329.
AB  - Interpersonal aggression is assessed paleoepidemiologically in a large skeletal
      population from the CA-ALA-329 site located on the southeastern side of San
      Francisco Bay, California. This comprehensive analysis included all currently
      recognized skeletal criteria, including craniofacial fracture, projectile injury,
      forearm fracture, and perimortem bone modification. Craniofacial injury is
      moderately common, showing an adult prevalence of 9.0% with facial lesions
      accounting for >50% of involvement. Clinical studies suggest that such separate
      evaluation of facial involvement provides a useful perspective for understanding
      patterns of interpersonal aggression. In this group male facial involvement is
      significantly greater than in females, paralleling the pattern found widely in
      contemporary populations as well as in African apes. When compared to other North
      American skeletal samples the prevalence of adult cranial vault injury (3.3%) and
      especially projectile injury (4.4%) are quite high. However, well documented
      populations from southern California show markedly higher prevalence for both
      types of skeletal markers of aggression. Forearm fracture is also assessed using
      a rigorous radiographic methodology and results suggest that these injuries are
      not reliable indicators of interpersonal aggression. Lastly, perimortem bone
      modification was not observed in this population, although it has been recorded
      from other (older) sites nearby. This study provides an evaluation of multiple
      skeletal markers of interpersonal aggression in the largest sample from a single
      site yet reported in North America and, joined with consideration of cultural
      context, helps further illuminate both geographic and temporal patterns of
      interpersonal aggression in California.

PMID- 19170214
TI  - Spectrum of fibrosing diffuse parenchymal lung disease.
AB  - The interstitial lung diseases are a heterogeneous group of disorders
      characterized by inflammation and/or fibrosis of the pulmonary interstitium. In
      2002, the American Thoracic Society and the European Respiratory Society revised
      the classification of interstitial lung diseases and introduced the term diffuse
      parenchymal lung disease. The idiopathic interstitial pneumonias are a subtype of
      diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are
      subdivided into usual interstitial pneumonia (with its clinical counterpart
      idiopathic interstitial pneumonia), nonspecific interstitial pneumonia,
      cryptogenic organizing pneumonia, acute interstitial pneumonia, desquamative
      interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, and
      lymphocytic pneumonia. Sarcoidosis and hypersensitivity pneumonitis are the 2
      most common granulomatous diffuse parenchymal lung diseases. Rheumatoid
      arthritis, systemic sclerosis, and dermatomyositis/polymyositis (causing
      antisynthetase syndrome) are diffuse parenchymal lung diseases of known
      association because these conditions are associated with connective tissue
      disease. Hermansky-Pudlak syndrome is a rare genetic diffuse parenchymal lung
      disease characterized by the clinical triad of pulmonary disease, oculocutaneous
      albinism, and bleeding diathesis. This review provides an overview of the chronic
      fibrosing diffuse parenchymal lung diseases. Its primary objective is to
      illuminate the clinical challenges encountered by clinicians who manage the
      diffuse parenchymal lung diseases regularly and to offer potential solutions to
      those challenges. Treatment for the diffuse parenchymal lung diseases is limited,
      and for many patients with end-stage disease, lung transplantation remains the
      best option. Although much has been learned about the diffuse parenchymal lung
      diseases during the past decade, research in these diseases is urgently needed.

PMID- 19170215
TI  - Gastroesophageal reflux disease and idiopathic pulmonary fibrosis.
AB  - Gastroesophageal reflux disease occurs with a higher prevalence in patients with
      idiopathic pulmonary fibrosis than in matched controls. Silent reflux occurs in
      about a third of patients with significant gastroesophageal reflux disease; thus,
      objective measurements are required to evaluate gastroesophageal reflux disease
      in patients with advanced lung diseases. We provide here a detailed description
      of acid and non-acid reflux and the diagnostic evaluation for pulmonologists and
      lung transplant surgeons suspecting reflux as a contributing factor in advanced
      lung diseases. We review the evidence for gastroesophageal reflux disease causing
      idiopathic pulmonary fibrosis and other select pulmonary diseases and the
      potential role of antireflux surgery in the management of advanced lung disease
      and transplant patients.

PMID- 19170216
TI  - "End-stage" pulmonary fibrosis in sarcoidosis.
AB  - Pulmonary fibrosis is an unusual "end stage" in patients with sarcoidosis.
      Fibrosis occurs in a minority of patients, and presents with a unique physiologic
      combination of airways dysfunction (obstruction) superimposed on the more common
      restrictive dysfunction. Imagin techniques are essential to the diagnosis,
      assessment and treatment of pulmonary fibrosis. Standard chest radiographs and CT
      scans may reveal streaks, bullae, cephalad retraction of the hilar areas,
      deviation of the trachea and tented diaphragm. Positive gallium and PET scans
      indicate residual reversible granulomatous disease and are important guides to
      therapy decisions. Treatment, usually with corticosteroids, is effective in those
      patients with positive scans, but fibrosis does not improve with any treatment.
      With severe functional impariment and patient disability, pulmonary hypertension
      and right heart failure may supervene for which the patient will require
      treatment. Oxygen, careful diuresis, sildenafil and bosentan may be salutary.
      These patients are candidates for lung transplantation.

PMID- 19170217
TI  - High resolution computed tomography in idiopathic interstitial pneumonias.
AB  - In June 2001, using an "international multidisciplinary consensus," the American
      Thoracic Society and European Respiratory Society classified the idiopathic
      interstitial pneumonias (Am J Respir Crit Care Med 2002;165:277-304). The
      American Thoracic Society and European Respiratory Society coined the term
      idiopathic interstitial pneumonias because the diseases in question have both
      unknown etiologies and various combinations of inflammation and fibrosis within
      the lung parenchyma. The consensus included the development of a classification
      standard of the interstitial pneumonias and discussed the role of surgical lung
      biopsy and bronchoalveolar lavage evaluation. The classification of idiopathic
      interstitial pneumonias is based on histologic criteria, which correlate to
      imaging patterns on high-resolution computed tomography. The group of lung
      diseases under the umbrella of idiopathic interstitial pneumonias includes the
      following: usual interstitial pneumonia, nonspecific interstitial pneumonia,
      desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung
      disease, acute interstitial pneumonia, cryptogenic organizing pneumonia, and
      lymphoid interstitial pneumonia.

PMID- 19170218
TI  - Comorbidities of advanced lung disease.
AB  - Lung disease in advanced stages is often accompanied by multiple comorbidities.
      Often, these processes lead to significant morbidity and occasionally mortality.
      Symptoms of pulmonary comorbidities, including pulmonary embolus, pulmonary
      hypertension, sleep-disordered breathing, and lung malignancy, may be intertwined
      with symptoms of advancing lung disease. However, the occurrence of
      extrapulmonary processes, including depression, diabetes mellitus, osteoporosis,
      and gastroesophageal reflux disease, may be subtle. Clinicians caring for
      advanced lung disease should be aware of the many comorbid processes that may
      accompany advancing lung disease.

PMID- 19170219
TI  - Advanced lung disease: quality of life and role of palliative care.
AB  - Advanced restrictive lung diseases remain a challenge for both the clinician and
      patient alike. Because there are few available treatment options that prolong
      survival for patients with diseases such as idiopathic pulmonary fibrosis,
      improvement in quality of life and palliation of significant symptoms become
      realistic treatment goals. Several validated instruments that assess quality of
      life and health-related quality of life have demonstrated the dramatic impact
      that lung disease has on patients. Quality-of-life assessments of patients with
      interstitial lung disease have commonly cited respiratory complaints as
      problematic, but other distressing symptoms often not addressed include fear,
      social isolation, anxiety, and depression. Not only do respiratory symptoms limit
      this patient population, but the awareness of decreased independence and ability
      for social participation also has an impact on the quality of life. Some patients
      describe a deepened spiritual well-being during their disease process; however,
      many patients' mental health suffers with experiences of fear, worry, anxiety,
      and panic. Many patients express desire for more attention to end-of-life issues
      from their physicians. Fears of worsening symptoms and suffocation exist with an
      expressed desire by most to die peacefully with symptom control. Interventions to
      improve quality of life are largely directed at symptom control. Pharmacologic
      and nonpharmacologic interventions have been helpful in relieving dyspnea.
      Studies have demonstrated that the use of supplemental oxygen in the face of
      advancing hypoxemia can have both positive and negative effects on quality of
      life. Patients using nasal prongs describe feelings of self-consciousness,
      embarrassment, and social withdrawal. Pulmonary rehabilitation is recommended,
      with some studies noting increased quality-of-life scores and decreased
      sensations of dyspnea. Sleep deprivation and poor sleep quality also have a
      negative impact on quality of life. Recognition and correction of nocturnal
      hypoxemia and other sleep disturbances should enhance quality of life in patients
      with restrictive lung disease; however, there is currently no evidence to support
      this claim. End-of-life care needs more attention by clinicians in the decision
      making and preparatory phase. Physicians need to maintain their focus on quality
      of-life issues as medical management shifts from curative therapies to comfort
      management therapies. Palliative care and hospice appear to be underused in
      patients with advanced diseases other than cancer. Because the only curative
      option for some end-stage restrictive lung diseases is lung transplantation, if
      transplantation is not an option, palliation of symptoms and hospice care may
      offer patients and families the opportunity to die with dignity and comfort.

PMID- 19170220
TI  - Fistula experience in Niger: how we overcame an ethical dilemma.

PMID- 19170221
TI  - Acetaminophen hepatotoxicity: current management.

PMID- 19170222
TI  - Healthcare-associated Infections: epidemiology, prevention, and therapy.
AB  - Reducing nosocomial infection rates is a major component of healthcare
      improvement. This article reviews the epidemiology, prevention, and therapy for
      some of the most common healthcare-associated infections, including central line
      associated bloodstream infections and catheter-associated urinary tract
      infections, and 3 common organisms: methicillin-resistant Staphylococcus aureus,
      multidrug- resistant gram-negative bacteria, and Clostridium difficile.

PMID- 19170223
TI  - Guiding cell migration in 3D: a collagen matrix with graded directional
      stiffness.
AB  - While matrix stiffness has been implicated in cell adhesion and migration, most
      studies have focused on the effects of substrate stiffness in 2D. The present
      work describes a novel continuous stiffness gradient model for studying such
      processes in 3D. Wedge-shaped collagen scaffolds were compressed to produce
      sheets of a desired (0.1 mm) uniform thickness, but with increasing collagen
      density along the length of the sheet. Dynamic mechanical analysis, carried out
      on 1 mm wide strips obtained from the two ends and the middle of each sheet,
      showed that the elastic modulus increased from 1057 +/- 487 kPa to 2305 +/- 693
      kPa at the soft and stiff end respectively and was 1835 +/- 31 kPa in the middle.
      In constructs seeded with agarose marker beads prior to compression, mean agarose
      bead density rose from 10 +/- 1 to 71 +/- 12 at the soft and stiff end
      respectively and was 19 +/- 5 in the middle, indicating successful engineering of
      a density gradient corresponding to the measured stiffness gradient. Growth
      arrested human dermal fibroblasts, initially seeded evenly within such
      constructs, accumulated preferentially towards the stiff part of the gradient
      after 3 and 6 days in culture. Durotactic migration was significant after 6 days.
      This model provides a new means for studying cellular mechanotaxis and patterning
      cells which is controllable, biomimetic and in 3D.

PMID- 19170224
TI  - Fibroblast elongation and dendritic extensions in constrained versus
      unconstrained microtissues.
AB  - Cytoskeletal tension is fundamental to many biological processes, including germ
      layer sorting during embryogenesis [Krieg et al., 2008]. In vitro, such tension
      influences cell sorting in self-assembled, 3D microtissues and can be of
      sufficient magnitude to cause complex-shaped microtissue failure [Dean et al.,
      2007]. To examine the process of failure under cell-derived tension, we subjected
      normal human fibroblasts (NHFs) to directed self-assembly [Dean et al., 2007] in
      micro-molds designed to yield self-constraining microtissues. As cells contracted
      in this assay, the constrained microtissues narrowed, thinned and ultimately
      failed at their midpoints. By adding small numbers of GFP+ cells, changes in cell
      movement and morphology were assessed and compared to those of unconstrained
      microtissues. We found that cells formed numerous dendritic extensions within an
      hour of self-assembly and retracted these extensions as they elongated up to 30
      times their initial diameter ( approximately 600 microm) just prior to failure.
      Surprisingly, significant coordination in cell motility was observed over large
      distances within microtissues. Pharmacologic interventions showed that failure
      was myosin II and Rho kinase dependent and inhibition of failure resulted in
      shorter cells with greater numbers of extensions. These findings further our
      understanding of cellular self-assembly and introduce the use of GFP+ cells with
      directed self-assembly as a scaffold-free analogue to fibroblast-populated
      collagen gels (FPCGs).

PMID- 19170225
TI  - Initiation of epoetin-alpha therapy at a starting dose of 120,000 units once
      every 3 weeks in patients with cancer receiving chemotherapy: an open-label,
      multicenter study with randomized and nonrandomized treatment arms.
AB  - BACKGROUND: Epoetin-alpha initiated once weekly, followed by once-every-3-weeks
      maintenance, was effective and well tolerated for chemotherapy-induced anemia.
      This study evaluated a starting dose of epoetin-alpha 120,000 U once every 3
      weeks for chemotherapy-induced anemia using early and late initiation regimens.
      METHODS: Patients with baseline hemoglobin 11.0-12.0 g/dL were randomly assigned
      to early intervention with immediate epoetin-alpha (n = 68) or to standard
      intervention with epoetin-alpha when hemoglobin decreased to <11 g/dL (n = 68). A
      third group of patients with baseline hemoglobin <11 g/dL (n = 50) were enrolled
      but not randomized; epoetin-alpha was initiated immediately. The primary endpoint
      was mean proportion of hemoglobin values within the target range (11.0-13.0 g/dL)
      among randomized patients. RESULTS: The mean proportion of hemoglobin values in
      range through week 16 was 60% in each randomized group. Mean hemoglobin by week
      showed similar increases over the study. Blood transfusions were administered in
      9%, 8%, and 24% of patients in the early, standard, and nonrandomized groups.
      Mean epoetin-alpha doses were similar between treatment groups. Dose reductions
      and withholds were more common in the early intervention group. Adverse events
      (eg, diarrhea, fatigue, nausea) were consistent with the safety profile for
      epoetin-alpha . Clinically relevant thrombotic vascular events (regardless of
      relationship to study treatment) were reported for 9%, 12%, and 12% of patients
      in the early, standard, and nonrandomized groups. CONCLUSIONS: Early and standard
      intervention with epoetin-alpha, administered once every 3 weeks, increased and
      maintained hemoglobin levels within 11.0-13.0 g/dL in patients with chemotherapy
      induced anemia.

PMID- 19170227
TI  - Identification and expression profiling of microRNAs during bovine oocyte
      maturation using heterologous approach.
AB  - The accumulation of maternal mRNA and protein during oogenesis for supporting
      oocyte maturation and the newly fertilised zygote marks the beginning of
      developmental process in mammals. MicroRNAs (approximately 18-22 nt long) which
      are known for post-transcriptional gene regulation are evidenced for their
      essential role during animal development. We, therefore, aimed to investigate the
      expression of miRNAs in immature and in vitro matured bovine oocytes, using
      heterologous miRNA array platform. To attain this, we used a mercury locked
      nucleic acids (LNA) array (Exiqon, Vedbaek, Denmark) microarray that consist of
      454 capture probes for human, mouse and rat miRNAs as registered and annotated in
      the miRBase release 8.0 at The Wellcome Trust Sanger Institute. Our result
      revealed the differential expression of 59 miRNAs, of which 31 and 28 miRNAs were
      found to be preferentially expressed in immature and matured oocytes,
      respectively. Here, we also report the identification of 32 orthologous miRNAs
      using a heterologous approach. Expression profiling of selected miRNAs during
      preimplantation stage embryos showed a distinct temporal expression pattern.
      After target prediction for selected candidate miRNAs high ranking target mRNA
      were quantified in immature and matured oocytes and showed a reciprocal
      expression pattern between the miRNA and the predicted targets suggesting a cause
      and effect relationship.

PMID- 19170226
TI  - Phase 1 study of oxaliplatin and irinotecan in pediatric patients with refractory
      solid tumors: a children's oncology group study.
AB  - BACKGROUND: For this report, the authors estimated the maximum tolerated dose
      (MTD) and investigated the toxicities of oxaliplatin combined with irinotecan in
      children with refractory solid tumors. METHODS: Oxaliplatin was administered on
      Days 1 and 8 in combination with irinotecan on Days 1 through 5 and Days 8
      through 12 of a 21-day cycle. An oral cephalosporin was administered daily to
      ameliorate irinotecan-associated diarrhea. Pharmacokinetic studies of oxaliplatin
      and uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)
      genotyping were performed. RESULTS: Thirteen patients were enrolled. Dose
      limiting diarrhea (n = 3), serum lipase elevation (n = 3), serum amylase
      elevation (n = 2), colitis, abdominal pain, and headache (n = 1 each) occurred at
      the first dose level (oxaliplatin at a dose of 60 mg/m(2); irinotecan at a dose
      of 20 mg/m(2)). Only 1 of 7 patients who received reduced doses of both agents
      (40 mg/m(2)/dose oxaliplatin; 15 mg/m(2)/dose irinotecan) experienced a dose
      limiting toxicity (DLT): diarrhea. When the oxaliplatin dose was re-escalated (60
      mg/m(2)) with irinotecan at a dose of 15 mg/m(2), 2 of 3 patients had a DLT (1
      episode of diarrhea, 1 episode of hypokalemia). Myelosuppression was minimal. One
      patient had a complete response, and another patient had stable disease for 6
      cycles of therapy. The median oxaliplatin area under the concentration versus
      time curve (AUC(0-->infinity)) was 5.9 microg . hour/mL (range, 1.8-7.6 microg .
      hour/mL). The frequency of the 6/6, 6/7, and 7/7 UGT1A1 promoter genotypes was 5
      of 10, 4 of 10, and 1 of 10, respectively. CONCLUSIONS: The oxaliplatin MTD was
      40 mg/m(2) per dose on Days 1 and 8 in combination with irinotecan 15 mg/m(2) per
      dose on Days 1-5 and Days 8-12. There was some evidence of antitumor activity;
      however, severe toxicity, both expected (diarrhea) and unexpected (elevation in
      pancreatic enzymes), was observed.

PMID- 19170229
TI  - Noninvasive evaluation of oral lesions using depth-sensitive optical
      spectroscopy.
AB  - BACKGROUND: Optical spectroscopy is a noninvasive technique with potential
      applications for diagnosis of oral dysplasia and early cancer. In this study, we
      evaluated the diagnostic performance of a depth-sensitive optical spectroscopy
      (DSOS) system for distinguishing dysplasia and carcinoma from non-neoplastic oral
      mucosa. METHODS: Patients with oral lesions and volunteers without any oral
      abnormalities were recruited to participate. Autofluorescence and diffuse
      reflectance spectra of selected oral sites were measured using the DSOS system. A
      total of 424 oral sites in 124 subjects were measured and analyzed, including 154
      sites in 60 patients with oral lesions and 270 sites in 64 normal volunteers.
      Measured optical spectra were used to develop computer-based algorithms to
      identify the presence of dysplasia or cancer. Sensitivity and specificity were
      calculated using a gold standard of histopathology for patient sites and clinical
      impression for normal volunteer sites. RESULTS: Differences in oral spectra were
      observed in: (1) neoplastic versus nonneoplastic sites, (2) keratinized versus
      nonkeratinized tissue, and (3) shallow versus deep depths within oral tissue.
      Algorithms based on spectra from 310 nonkeratinized anatomic sites (buccal,
      tongue, floor of mouth, and lip) yielded an area under the receiver operating
      characteristic curve of 0.96 in the training set and 0.93 in the validation set.
      CONCLUSIONS: The ability to selectively target epithelial and shallow stromal
      depth regions appeared to be diagnostically useful. For nonkeratinized oral
      sites, the sensitivity and specificity of this objective diagnostic technique
      were comparable to that of clinical diagnosis by expert observers. Thus, DSOS has
      potential to augment oral cancer screening efforts in community settings.

PMID- 19170230
TI  - The EML4-ALK fusion gene is involved in various histologic types of lung cancers
      from nonsmokers with wild-type EGFR and KRAS.
AB  - BACKGROUND: The echinoderm microtubule-associated protein-like 4-anaplastic
      lymphoma kinase (EML4-ALK) fusion gene resulting from the chromosome inversion
      inv(2)(p21;p23) recently was identified in nonsmall cell lung cancer (NSCLC). The
      authors of this study investigated the frequency, genetic and clinicopathologic
      profiles of EML4-ALK in Chinese patients with NSCLC. METHODS: EML4-ALK was
      investigated in 266 resected primary NSCLC, including adenocarcinomas (AD),
      lymphoepithelioma-like carcinomas, squamous cell carcinomas, mucoepidermoid
      carcinomas, and adenosquamous carcinomas, by reverse transcriptase-polymerase
      chain reaction and was verified by sequencing. EML4-ALK protein expression was
      studied by immunohistochemistry. RESULTS: Thirteen tumors (4.9%) had EML4-ALK
      comprising 4 fusion transcript variants with fusion of the variable segments from
      5' EML4 to 3' ALK and with preservation of the ALK kinase domain. The most common
      variant consisted of 8 tumors with variant 3 that involved EML4 exon 6. The
      others included 2 tumors with variant 1 (exon 13), 2 tumors with variant 2 (exon
      20), and 1 tumor with the novel variant 5 (exon 18). There were 11 ADs and 2
      unusual carcinomas with mixed squamous and glandular components.
      Immunohistochemistry demonstrated diffuse ALK fusion proteins in the tumor cell
      cytoplasm. EML4-ALK was associated with nonsmokers (P = .009). Tumors with the
      fusion gene had the wild-type epidermal growth factor receptor (EGFR) (P = .001)
      and v-Ki-ras2/Kirsten rat sarcoma viral oncogene homolog (KRAS) genes. Patients
      who had EML4-ALK-positive AD had a younger median age (P = .018) compared with
      patients who did not have the fusion gene. CONCLUSIONS: The EML4-ALK fusion gene
      was present in various histologic types of NSCLC. It occurred in mutual exclusion
      to EGFR and KRAS mutations and was associated with nonsmokers. The authors
      concluded that EML4-ALK may be useful for predicting the potential response to
      ALK inhibitors as a therapeutic option for patients with lung cancer.

PMID- 19170231
TI  - Colcemid-treatment of heifer oocytes enhances nuclear transfer embryonic
      development, establishment of pregnancy and development to term.
AB  - Four experiments were designed to examine the effects of colcemid, a microtubule
      assembly inhibitor, on the development of bovine nuclear transfer (NT) embryos in
      vitro and in vivo. Recipient oocytes matured at different times were exposed to
      colcemid. Approximately 80-93% of the exposed oocytes, with or without the first
      polar body (PB1), developed obvious membrane projections. In Experiment 1,
      oocytes matured for either 14-15 or 16-17 hr, treated with colcemid and used as
      recipient cytoplasm for NT resulted in over 40% blastocyst development. In
      Experiment 2, oocytes matured for 16-17 hr were treated with either 0.2 or 0.4
      microg/ml colcemid for 2-3 or 5-6 hr, respectively. The percentages of blastocyst
      development (39-42%) were not statistically different among the different
      colcemid treatment groups, but were both higher (P < 0.05) than the control group
      (30%). Colcemid concentrations and length of colcemid treatment of oocytes did
      not affect their ability to support NT embryo development to the blastocyst and
      hatched blastocyst stages. Results from Experiment 3 indicate that semi-defined
      medium increases morula and blastocyst development of NT embryos derived from
      colcemid-treated oocytes under 5% CO2 in air atmosphere. In addition, cell
      numbers of blastocysts in colcemid-treated groups were numerically higher than
      the control groups. After embryo transfer, higher (P < 0.05) pregnant rates were
      obtained from the colcemid-treated group than the nontreated group. Five of 40
      recipients (12.5%) which received embryos from colcemid-treated oocytes delivered
      healthy calves, significantly higher than those recipients (3.3%) that received
      embryos derived from nontreated oocytes.

PMID- 19170233
TI  - Concurrent lobular neoplasia increases the risk of ipsilateral breast cancer
      recurrence in patients with ductal carcinoma in situ treated with breast
      conserving therapy.
AB  - BACKGROUND: Multiple clinicopathologic factors have been analyzed for their
      association with an increased risk of ipsilateral breast tumor recurrence (IBTR)
      after women receive breast-conserving treatment (BCT) for ductal carcinoma in
      situ (DCIS). The reported incidence of proliferative lesions, such as atypical
      ductal hyperplasia (ADH), columnar cell changes (CCC), and lobular neoplasia
      associated with breast cancer, has been as high as 23%; however, the relevance of
      these lesions on the natural history of DCIS and the risk of IBTR remains
      unknown. METHODS: Two hundred ninety-four patients with DCIS who received BCT
      between 1991 and 1995 were identified from the authors' institutional database.
      Slides were reviewed by a dedicated breast pathologist with particular attention
      to the presence of lobular neoplasia, ADH, and CCC. The actuarial 5-, 10-, and 15
      year IBTR rates were calculated using the Kaplan-Meier method and were compared
      using the log-rank test. RESULTS: Concurrent lobular neoplasia was present in 41
      of 294 patients (14%), ADH was present in 37 of 294 patients (13%), and CCC was
      present in 71 of 294 patients (24%). The median follow-up was 11 years. IBTR
      occurred in 40 of 227 patients without lobular neoplasia (18%) versus 15 of 41
      patients with lobular neoplasia (37%; P=.005; hazard ratio [HR], 2.49). The 5-,
      10-, and 15-year cumulative incidence rates of IBTR were twice as high in women
      who had DCIS and lobular neoplasia compared with women who had DCIS alone
      (P=.002). Concomitant ADH (HR, 1.53) and CCC (HR, 1.24) were not associated
      significantly with IBTR (P=.20 and P=.44, respectively). CONCLUSIONS: Concurrent
      lobular neoplasia is associated with a significantly higher risk of IBTR in women
      with DCIS who received BCT. Women with coexisting DCIS and lobular neoplasia who
      receive BCT should consider using additional risk-reducing strategies.

PMID- 19170232
TI  - Health-related quality of life in long-term breast cancer survivors: differences
      by adjuvant chemotherapy dose in Cancer and Leukemia Group B study 8541.
AB  - BACKGROUND: The Survivor's Health and Reaction (SHARE) study examined health
      related quality of life (HRQL) in breast cancer patients who had participated in
      Cancer and Leukemia Group B Trial 8541 from 1985 to 1991. METHODS: In total, 245
      survivors (78% of eligible patients) who were 9.4 to 16.5 years postdiagnosis
      (mean, 12.5 years postdiagnosis) completed HRQL surveys relating to 5 domains.
      Analyses examined HRQL domains according to 3 different chemotherapy dose levels
      that were administered in the original treatment trial: low-dose
      cyclophosphamide, doxorubicin, and fluorouracil (CAF) at 300 mg/m(2), 30 mg/m(2),
      and 300 x 2 mg/m(2), respectively, over 4 cycles; standard-dose CAF at 400
      mg/m(2), 40 mg/m(2), and 400 x 2 mg/m(2), respectively, over 6 cycles; and high
      dose CAF at 600 mg/m(2), 60 mg/m(2) and 600 x 2 mg/m(2), respectively, over 4
      cycles. RESULTS: In univariate analyses, a statistically significant difference
      was observed on the Medical Outcomes Study 36-item short form Physical Role
      Functioning subscale by treatment group, with lower mean scores in the standard
      treatment arm (mean, 65.05) compared with mean scores in the low-dose arm (mean,
      74.66) and the high-dose arm (mean, 84.94; P.0001). However, multivariate
      analysis revealed that treatment arm no longer was statistically significant,
      whereas the following factors were associated with decreased physical role
      functioning: age >or=60 years (odds ratio [OR], 3.55; P = .006), increased
      comorbidity interference total score (OR, 1.64; P = .005), lower vitality (OR,
      1.05; P = .0002), and increased menopausal symptoms (OR, 1.04 P = .02).
      CONCLUSIONS: At 9.4-16.5 years after their original diagnosis, differences in
      physical role functioning among breast cancer survivors who had received 3
      different dose levels of chemotherapy were explained by clinical and demographic
      variables, such as age, fatigue, menopausal symptoms, and comorbidities.
      Prospective studies are needed to further assess the role of these factors in
      explaining HRQL and physical role functioning among long-term survivors.

PMID- 19170234
TI  - Polyamines protect rat embryo in vitro from high glucose-induced developmental
      delay and dysmorphogenesis.
AB  - BACKGROUND: Pregnancy in mammals with diabetes mellitus results in low birth
      weight, malformations, and intrauterine death. Parenteral application of natural
      polyamines or their precursor, L-arginine, to diabetic pregnant rats partially
      prevents the alterations of development caused by diabetes mellitus. This
      experiment has been designed to understand if this preventive action also occurs
      in rat whole embryo in culture. MATERIALS AND METHODS: Rat embryos of gestational
      day 10 were cultured for 24 h in normal medium, high glucose medium, or high
      glucose medium supplemented with polyamines or L-arginine, and furthermore embryo
      growth and development were evaluated. RESULTS: L-arginine and putrescine
      partially prevents the dysmorphogenic effects of high glucose, whereas spermidine
      and spermine prevent these effects almost completely. CONCLUSIONS: Polyamines
      directly protect the embryo from the toxic effect of high glucose concentration
      on growth and development, although the mechanism remains to be elucidated.

PMID- 19170235
TI  - Lobule type and subsequent breast cancer risk: results from the Nurses' Health
      Studies.
AB  - BACKGROUND: Lobules in normal breast tissue can be classified based on their
      degree of development, which may affect their susceptibility to carcinogenesis.
      However, few epidemiologic studies to date have addressed this. METHODS: The
      authors examined the association between lobule type and subsequent breast cancer
      risk in a nested case-control study of benign breast disease (BBD) and breast
      cancer within the Nurses' Health Studies (200 cases, 915 controls). Benign breast
      biopsy slides were reviewed by pathologists, and normal terminal duct lobular
      units were classified as having no type 1 lobules, mixed lobule types, or
      predominant type 1 and no type 3 lobules. Logistic regression was used to compute
      odds ratios (ORs) and 95% confidence intervals (CIs) for the association between
      lobule type and breast cancer risk. RESULTS: Women with predominant type 1 and no
      type 3 lobules (54 cases, 321 controls) had a decreased risk of breast cancer
      compared with those with no type 1 lobules or mixed lobule types (OR=0.63; 95%
      CI, 0.44-0.91), although this was attenuated after adjustment for histologic
      category of BBD (OR=0.71; 95% CI, 0.49-1.02). Having predominant type 1 lobules
      and no type 3 lobules was associated with a similar risk reduction for all
      categories of BBD (nonproliferative: OR=0.73 [95% CI, 0.36-1.50]; proliferative
      without atypia: OR=0.80 [95% CI, 0.47-1.35]; and atypical hyperplasia: OR=0.61
      [95% CI, 0.28-1.35]). CONCLUSIONS: These results provided preliminary evidence
      that lobule type may be an important marker of breast cancer risk in women with
      BBD.

PMID- 19170236
TI  - Proliferation predicts failure-free survival in mantle cell lymphoma patients
      treated with rituximab plus hyperfractionated cyclophosphamide, vincristine,
      doxorubicin, and dexamethasone alternating with rituximab plus high-dose
      methotrexate and cytarabine.
AB  - BACKGROUND: It has been demonstrated that the tumor proliferation index has
      prognostic significance in patients with mantle cell lymphoma (MCL). Patients in
      most of studies, however, have been treated with relatively traditional
      chemotherapy regimens. At the authors' institution, patients with MCL received an
      aggressive chemotherapy regimen: rituximab plus hyperfractionated
      cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with
      rituximab plus high-dose methotrexate and cytarabine (R-hyper-CVAD). METHODS: The
      authors assessed the proliferation rate of MCL using immunohistochemistry and an
      antibody specific for Ki-67 in 71 untreated patients who subsequently received R
      hyper-CVAD. The study group included 59 patients who had classic MCL and 12
      patients who had the blastoid variant of MCL. RESULTS: For the entire study group
      and for the group of patients with classic MCL, a proliferation index of >20% Ki
      67-positive cells was correlated significantly with shorter failure-free
      survival. There was no correlation between the proliferation index and overall
      survival. CONCLUSIONS: The current results indicated that the proliferation index
      in patients with MCL predicted prognosis in those who uniformly received the R
      hyper-CVAD chemotherapy regimen.

PMID- 19170237
TI  - Centromere protein H is a novel prognostic marker for human nonsmall cell lung
      cancer progression and overall patient survival.
AB  - BACKGROUND: Lung cancer is 1 of the leading causes of cancer death worldwide, and
      the high mortality from this disease is caused mainly by the lack of efficient
      diagnostic strategies for early-stage lung cancer. The objective of the current
      study was to investigate the expression pattern and clinicopathologic
      significance of centromere protein H (CENP-H) in patients with nonsmall cell lung
      cancer (NSCLC). METHODS: The expression profile of CENP-H in normal lung
      epithelial cells, NSCLC cell lines, NSCLC tissues, and adjacent noncancerous lung
      tissues were detected by reverse transcription-polymerase chain reaction (RT
      PCR), real-time RT-PCR, and Western blot analysis. The expression level of CENP-H
      in 223 NSCLC tissues was measured by immunohistochemistry staining. Statistical
      analysis was performed to evaluate the clinicopathologic significance of CENP-H.
      RESULTS: The expression level of CENP-H was much higher in cancer cell lines and
      lung cancer tissues than that in normal cells and adjacent noncancerous lung
      tissues, respectively. Immunohistochemical analysis revealed positive CENP-H
      expression in 118 of 223 NSCLC tissues (52.9%). Statistical analysis revealed
      that CENP-H expression was correlated strongly with clinical stage (P=.018),
      tumor classification (P=.03), and Ki-67 expression (P < .001). Patients with
      lower CENP-H expression had better overall survival than patients with higher
      CENP-H expression. Further analysis suggested that CENP-H could predict prognosis
      only in patients with early-stage disease. Multivariate analysis suggested that
      CENP-H expression was an independent prognostic marker for survival in patients
      with NSCLC. CONCLUSIONS: The current results demonstrated that high CENP-H
      protein expression was related to poor outcome in patients with NSCLC. CENP-H may
      be used as a prognostic biomarker for patients lung patients, especially those
      with early-stage NSCLC.

PMID- 19170238
TI  - Increased risk of high-grade dermatologic toxicities with radiation plus
      epidermal growth factor receptor inhibitor therapy.
AB  - BACKGROUND: The addition of epidermal growth factor receptor (EGFR) inhibitors to
      radiotherapy has produced increased locoregional control and has reduced
      mortality from various solid tumors with few additional toxicities. Although
      anecdotal reports have suggested increased radiation dermatitis, the overall
      effect of these regimens on dermatologic toxicities has not been ascertained.
      METHODS: Dermatologic toxicity data were analyzed from abstracts presented at the
      annual meetings of the American Society of Clinical Oncology, the American
      Society of Therapeutic Radiology and Oncology, Cochrane Collaboration, MEDLINE,
      and EMBASE databases. Phase 1, 2, and 3 trials that reported on radiation
      dermatitis, rash, and mucositis were included. Collaborative group, phase 3,
      randomized radiotherapy and chemoradiation trials served as controls. The summary
      incidence rate and relative risk were calculated using a random-effects or fixed
      effects model, depending on the heterogeneity of included studies. RESULTS: The
      summary incidence of high-grade radiation dermatitis in patients who received
      radiation plus EGFR inhibitors was 31.3% (95% confidence interval [95% CI], 17.7%
      49.1%), rash in 16.1% (95% CI, 12.8%-20.1%), and mucositis occurred in 52.7% (95%
      CI, 38.1%-66.9%). When the combination of radiotherapy plus EGFR inhibitors was
      compared with radiation alone, the risk ratio for radiation dermatitis was 2.38
      (95% CI, 1.8-3.2; P<.001), rash was 3.01 (95% CI, 2.0-4.6; P<.001), for mucositis
      it was 1.76 (95% CI, 1.5-2.0; P<.001), suggesting that there was an increased
      risk of dermatologic toxicities with the combined regimen. CONCLUSIONS: EGFR
      inhibitors combined with radiation were associated with a significant increase in
      the risk for high-grade radiation dermatitis, rash, and mucositis. Although
      increased rash is expected with EGFR inhibitors, in-field dermatitis and
      mucositis represent new safety concerns. Improved reporting and management
      strategies are critical for quality of life and the optimization of radiation
      plus EGFR inhibitor protocols.

PMID- 19170239
TI  - Grafting of antibacterial polymers on stainless steel via surface-initiated atom
      transfer radical polymerization for inhibiting biocorrosion by Desulfovibrio
      desulfuricans.
AB  - To enhance the biocorrosion resistance of stainless steel (SS) and to impart its
      surface with bactericidal function for inhibiting bacterial adhesion and biofilm
      formation, well-defined functional polymer brushes were grafted via surface
      initiated atom transfer radical polymerization (ATRP) from SS substrates. The
      trichlorosilane coupling agent, containing the alkyl halide ATRP initiator, was
      first immobilized on the hydroxylated SS (SS-OH) substrates for surface-initiated
      ATRP of (2-dimethylamino)ethyl methacrylate (DMAEMA). The tertiary amino groups
      of covalently immobilized DMAEMA polymer or P(DMAEMA), brushes on the SS
      substrates were quaternized with benzyl halide to produce the biocidal
      functionality. Alternatively, covalent coupling of viologen moieties to the
      tertiary amino groups of P(DMAEMA) brushes on the SS surface resulted in an
      increase in surface concentration of quaternary ammonium groups, accompanied by
      substantially enhanced antibacterial and anticorrosion capabilities against
      Desulfovibrio desulfuricans in anaerobic seawater, as revealed by antibacterial
      assay and electrochemical studies. With the inherent advantages of high corrosion
      resistance of SS, and the good antibacterial and anticorrosion capabilities of
      the viologen-quaternized P(DMAEMA) brushes, the functionalized SS is potentially
      useful in harsh seawater environments and for desalination plants.

PMID- 19170240
TI  - Self-renaturing enzymes: design of an enzyme-chaperone chimera as a new approach
      to enzyme stabilization.
AB  - Molecular chaperones in aqueous-organic mixtures can broaden the utility of
      biocatalysis by stabilizing enzymes in denaturing conditions. We have designed a
      self-renaturing enzyme-chaperone chimera consisting of penicillin amidase and a
      thermophilic chaperonin that functions in aqueous-organic mixtures. The flexible
      linker separating the enzyme and chaperone domains was optimized and the design
      was extended to incorporate a chitin binding domain to facilitate immobilization
      of the chimera to a chitin support. The initial specific activity of penicillin
      amidase was not compromised by the enzyme-chaperone fusion or by immobilization.
      The total turnover number of immobilized chimera for amoxicillin synthesis in
      aqueous-methanol mixtures was 2.8 times higher after 95 h than the total turnover
      number of the immobilized penicillin amidase lacking a chaperone domain.
      Similarly, in 32% methanol the soluble chimera was active for over three times
      longer than the enzyme alone. This approach could easily be extended to other
      enzyme systems.

PMID- 19170241
TI  - Dependence of alignment direction on magnitude of strain in esophageal smooth
      muscle cells.
AB  - The response of cells in vitro to mechanical forces has been the subject of much
      research using devices to exert controlled mechanical stimulation on cultured
      cells or isolated tissue. In this study, esophageal smooth muscle cells were
      seeded on flexible polyurethane membranes to form a confluent cell layer. The
      cells were then subjected to uniform cyclic stretch of varying magnitudes at a
      frequency of approximately five cycles per minute in a custom made mechatronic
      bioreactor, providing similar strains experienced in the in vivo mechanical
      environment of the esophagus. The results show that the orientation response is
      dependent on the magnitude of cyclic stretch applied. Smooth muscle cells showed
      parallel alignment to the force direction at low cyclic strains (2%) compared to
      the hill-valley morphology of static controls. At higher strains (5% and 10%
      magnitude), the cells exhibited a consistent alignment perpendicular to the
      strain. To our knowledge, this is the first time that the alignment direction's
      dependence on strain magnitude has been demonstrated. MTS analysis indicated that
      cell metabolism was reduced when mechanical strain was applied, and proliferation
      was inhibited by mechanical strain. Protein expression indicates a decrease in
      smooth muscle alpha-actin, indicative of changes in cell phenotype, an increase
      in vimentin, which is associated with increased cell motility, and an increase in
      desmin, indicating differentiation in stimulated cells.

PMID- 19170242
TI  - Nano-sized bacterial magnetic particles displaying pyruvate phosphate dikinase
      for pyrosequencing.
AB  - There is a high demand for inexpensive and high-throughput DNA sequencing
      technologies in molecular biology and applied biosciences. In this study, novel
      nano-sized magnetic particles displaying enzymes for pyrosequencing, a rather
      novel bioluminometric DNA sequencing method based on the sequencing-by-synthesis
      principle by employing a cascade of several enzymatic reactions, was developed. A
      highly thermostable enzyme, pyruvate phosphate dikinase (PPDK) which converts PPi
      to ATP was successfully expressed onto bacterial magnetic particles (BacMPs)
      using a novel protein display system of Magnetospirillum magneticum AMB-1. The
      enzymatic stability of BacMPs displaying PPDK (PPDK-BacMPs) to pH and temperature
      was evaluated and its broad range of properties was shown. Subsequently, PPDK
      BacMPs were applied in pyrosequencing and a target oligonucleotide was
      successfully sequenced. The PPDK enzyme displayed on BacMPs was shown to be
      recyclable in each sequence reaction as they can be manipulated by magnetic
      force. It was concluded that nano-sized PPDK-BacMPs are useful for the scale down
      of pyrosequencing reaction volumes, thus, permitting high-throughput. The
      recycling of enzymes was also shown to be promising and applicable for the
      development of an inexpensive DNA sequencing at a low running cost.

PMID- 19170243
TI  - Engineering of the yeast antioxidant enzyme Mpr1 for enhanced activity and
      stability.
AB  - The budding yeast Saccharomyces cerevisiae Sigma1278b has the MPR1 gene, which
      confers resistance to the proline analogue azetidine-2-carboxylate (AZC). This
      gene encodes an N-acetyltransferase Mpr1 that detoxifies AZC, and the homologous
      genes have been found in many yeasts. Recently, we found that Mpr1 protects yeast
      cells by reducing the intracellular reactive oxygen species (ROS) levels under
      oxidative stresses, such as heat-shock, freezing, or ethanol treatment. Unlike
      the known antioxidant enzymes, Mpr1 is thought to acetylate toxic metabolite(s)
      involved in ROS generation via oxidative events. To improve the enzymatic
      functions of Mpr1, we applied PCR random mutagenesis to MPR1. The mutagenized
      plasmid library was introduced into the S. cerevisiae S288C strain lacking MPR1,
      and we successfully isolated two Mpr1 variants with higher AZC resistance (K63R
      and F65L/L117V). Interestingly, overexpression of the K63R variant was found to
      increase cell viability or decrease intracellular ROS levels after exposure to
      H(2)O(2) or ethanol compared with the wild-type Mpr1. In vitro studies with the
      recombinant enzymes showed that the catalytic efficiency of the K63R variant for
      AZC and acetyl-CoA was higher than that of the wild-type Mpr1 and that the F65L
      mutation greatly enhanced the thermal stability. The mutational analysis and
      molecular modeling suggest that an alpha-helix containing Lys63 and Phe65 has
      important roles in the function of Mpr1. In addition, the wild-type and K63R
      variant Mpr1 reduced intracellular ROS levels under ethanol stress conditions on
      haploid sake yeast cells. These results suggest that engineering Mpr1 might be
      useful in breeding oxidative stress-tolerant yeast strains.

PMID- 19170244
TI  - Stepwise assembly of micropatterned co-cultures using photoresponsive culture
      surfaces and its application to hepatic tissue arrays.
AB  - Cell micropatterning, a method to place cells at arbitrary regions, is becoming
      an essential tool to conduct cell biology and tissue engineering. Conventional
      cell patterning techniques usually allow only single patterning with single cell
      type on the same culture surface. However, biomedical research today requires
      even sophisticated fabrication methods that require spatiotemporal control of
      multiple cell arrangements. Here we introduce in situ cell micropatterning system
      which enables stepwise cell patterning using a photoresponsive cell culture
      surface (PRCS) whose cell adhesiveness could be altered by the UV irradiation. To
      demonstrate an application to tissue engineering, a liver-mimic tissue array was
      fabricated and liver-specific gene expressions were quantified with real time
      PCR. Patterned co-culture systems composed of HepG2 spheroids with Balb/3T3 were
      fabricated, and the optimum spheroid diameter, which yielded the highest cellular
      functions, was determined to be 150 microm. After 20 days of patterned co-culture
      of HepG2 spheroids and Balb/3T3, CYP3A4 expression increased 50-fold higher than
      conventionally cultured HepG2; CYP3A4 expression was 20% higher than randomly co
      cultured HepG2 and Balb/3T3. Thus the combination of PRCS and the photomask-free
      irradiation apparatus showed the versatility of experimental setups and proved to
      be a powerful tool for biomedical studies.

PMID- 19170245
TI  - Selective bioparticle retention and characterization in a chip-integrated
      confocal ultrasonic cavity.
AB  - We demonstrate selective retention and positioning of cells or other bioparticles
      by ultrasonic manipulation in a microfluidic expansion chamber during
      microfluidic perfusion. The chamber is designed as a confocal ultrasonic
      resonator for maximum confinement of the ultrasonic force field at the chamber
      center, where the cells are trapped. We investigate the resonant modes in the
      expansion chamber and its connecting inlet channel by theoretical modeling and
      experimental verification during no-flow conditions. Furthermore, by triple
      frequency ultrasonic actuation during continuous microfluidic sample feeding, a
      set of several manipulation functions performed in series is demonstrated: sample
      bypass--injection--aggregation and retention--positioning. Finally, we
      demonstrate transillumination microscopy imaging of ultrasonically trapped COS-7
      cell aggregates.

PMID- 19170246
TI  - Effect of additives on the digestibility of corn stover solids following
      pretreatment by leading technologies.
AB  - Bovine serum albumin (BSA), Tween-20, and polyethylene glycol (PEG6000) were
      added to washed corn stover solids produced by ammonia fiber expansion (AFEX),
      ammonia recycled percolation (ARP), dilute sulfuric acid (DA), lime, controlled
      pH, and sulfur dioxide (SO(2)) pretreatments and to untreated corn stover (UT)
      and pure Avicel glucan prior to adding cellulase supplemented with beta
      glucosidase at an activity ratio of 1:2/g and a moderate enzyme loading of 16.1
      mg/g glucan in the raw corn stover. The additives were applied individually at
      150, 300, and 600 mg/g glucan in the pretreated solids and in combinations of
      equal amounts of each that totaled 600 mg/g. The greatest increase in total sugar
      release was by Tween-20 with SO(2) pretreated solids followed by PEG6000 with ARP
      solids and Tween-20 with lime solids. The effectiveness of the additives was
      observed to depend on the type of sugars left in the solids, suggesting that it
      may be more beneficial to use the mixture of these additives to realize a high
      total sugar yield. In addition, little enhancement in sugar release was possible
      beyond a loading of 150 mg additives/g glucan for most pretreatments, and
      combinations did not improve sugar release much over use of additives alone for
      all except SO(2). Additives were also found to significantly increase
      concentrations of cellobiose and cellooligomers after 72 h of Avicel hydrolysis.

PMID- 19170247
TI  - A new estimate of family disease history providing improved prediction of disease
      risks.
AB  - Complex diseases often aggregate within families and using the history of family
      members' disease can potentially increase the accuracy of the risk assessment and
      allow clinicians to better target on high risk individuals. However, available
      family risk scores do not reflect the age of disease onset, gender and family
      structures simultaneously. In this paper, we propose an alternative approach for
      a family risk score, the stratified log-rank family score (SLFS), which
      incorporates the age of disease onset of family members, gender differences and
      the relationship among family members. Via simulation, we demonstrate that the
      new SLFS is more closely associated with the true family risk for the disease and
      more robust to family sizes than two existing methods. We apply our proposed
      method and the two existing methods to a study of stroke and heart disease. The
      results show that assessing family history can improve the prediction of disease
      risks and the SLFS has strongest positive associations with both myocardial
      infarction and stroke.

PMID- 19170248
TI  - Spatial structure and NMR spectra of strained [2.2.2]cyclophanes.
AB  - The chemical shifts and coupling constants in the NMR spectra of the title
      compounds are influenced by their strain and the proximity of the aromatic rings.
      These parameters are studied by density functional theory (DFT) calculations for
      1-4 and measured for 3 and 4. We find that, in spite of the strain, the
      calculations reproduce the experimental values satisfactorily. This finding is of
      special importance for novel hypothetical molecules like hexahydrosuperphane 5
      for their future identification and in searches of hydrocarbons exhibiting
      unusual NMR parameters. Our results demonstrate the influence of strain on the
      parameters studied. Most proton and carbon chemical shifts for the molecules
      under study having nonplanar aromatic rings differ considerably from the
      corresponding values for the relatively unstrained trimethylbenzenes and
      ethylbenzene. In addition, the calculated values of the coupling constants
      through three bonds in most cases do not follow Karplus relation.

PMID- 19170249
TI  - Studies on drug-DNA complexes, adriamycin-d-(TGATCA)(2) and 4'-epiadriamycin-d
      (CGATCG)(2), by phosphorus-31 nuclear magnetic resonance spectroscopy.
AB  - The complexes of adriamycin-d-(TGATCA)(2) and 4'-epiadriamycin-d-(CGATCG)(2) are
      studied by one- and two-dimensional (31)P nuclear magnetic resonance spectroscopy
      (NMR) at 500 MHz in the temperature range 275-328 K and as a function of drug to
      DNA ratio (0.0-2.0). The binding of drug to DNA is clearly evident in (31)P-(31)P
      exchange NOESY spectra that shows two sets of resonances in slow chemical
      exchange. The phosphate resonances at the intercalating steps, T1pG2/C1pG2 and
      C5pA6/C5pG6, shift downfield up to 1.7 ppm and that at the adjacent step shift
      downfield up to 0.7 ppm, whereas the central phosphate A3pT4 is relatively
      unaffected. The variations of chemical shift with drug to DNA ratio and
      temperature as well as linewidths are different in each of the two complexes.
      These observations reflect change in population of B(I)/B(II) conformation,
      stretching of backbone torsional angle zeta, and distortions in O-P-O bond angles
      that occur on binding of drug to DNA. To the best of our knowledge, there are no
      solution studies on 4'-epiadriamycin, a better tolerated drug, and binding of
      daunomycin or its analogue to d-(TGATCA)(2) hexamer sequence. The studies report
      the use of (31)P NMR as a tool to differentiate various complexes. The specific
      differences may well be the reasons that are responsible for different antitumor
      action of these drugs due to different binding ability and distortions in DNA.

PMID- 19170250
TI  - In vitro biocompatibility of 45S5 Bioglass-derived glass-ceramic scaffolds coated
      with poly(3-hydroxybutyrate).
AB  - The aim of this work was to study the in vitro biocompatibility of glass-ceramic
      scaffolds based on 45S5 Bioglass, using a human osteosarcoma cell line (HOS
      TE85). The highly porous scaffolds were produced by the foam replication
      technique. Two different types of scaffolds with different porosities were
      analysed. They were coated with a biodegradable polymer, poly(3-hydroxybutyrate)
      (P(3HB)). The scaffold bioactivity was evaluated by soaking in a simulated body
      fluid (SBF) for different durations. Compression strength tests were performed
      before and after immersion in SBF. These experiments showed that the scaffolds
      are highly bioactive, as after a few days of immersion in SBF a hydroxyapatite
      like layer was formed on the scaffold's surface. It was also observed that P(3HB)
      coated samples exhibited higher values of compression strength than uncoated
      samples. Biocompatibility assessment was carried out by qualitative evaluation of
      cell morphology after different culture periods, using scanning electron
      microscopy, while cell proliferation was determined by using the AlamarBlue
      assay. Alkaline phosphatase (ALP) and osteocalcin (OC) assays were used as
      quantitative in vitro indicators of osteoblast function. Two different types of
      medium were used for ALP and OC tests: normal supplemented medium and osteogenic
      medium. HOS cells were seeded and cultured onto the scaffolds for up to 2 weeks.
      The AlamarBlue assay showed that cells were able to proliferate and grow on the
      scaffold surface. After 7 days in culture, the P(3HB)-coated samples had a higher
      number of cells on their surfaces than the uncoated samples. Regarding ALP- and
      OC-specific activity, no significant differences were found between samples with
      different pore sizes. All scaffolds containing osteogenic medium seemed to have a
      slightly higher level of ALP and OC concentration. These experiments confirmed
      that Bioglass/P(3HB) scaffolds have potential as osteoconductive tissue
      engineering substrates for maintenance and normal functioning of bone tissue.

PMID- 19170251
TI  - Genetic and biochemical analysis of a laboratory-selected spirodiclofen-resistant
      strain of Tetranychus urticae Koch (Acari: Tetranychidae).
AB  - BACKGROUND: Spirodiclofen is a selective, non-systemic acaricide from the new
      chemical class of tetronic acid derivatives. In order to develop strategies to
      minimise resistance in the field, a laboratory-selected spirodiclofen-resistant
      strain of the two-spotted spider mite, Tetranychus urticae Koch, was used to
      determine genetic, toxicological, biochemical and cross-resistance data. RESULTS:
      Selecting for spirodiclofen resistance in the laboratory yielded a strain (SR-VP)
      with a resistance ratio of 274, determined on the larval stage. The egg stage
      remained far more susceptible. No cross-resistance was found against other
      established acaricides, except for spiromesifen. Based on synergist experiments
      and enzyme assays, it appeared that especially P450 monooxygenases, but also
      esterases and glutathione-S-transferases, could be involved in the metabolic
      detoxification of spirodiclofen. Genetic analysis showed that the resistance is
      inherited as an intermediate trait under control of more than one gene.
      CONCLUSIONS: Resistance to spirodiclofen exceeded by far the recommended field
      rate. A good acaricide resistance management programme is necessary to prevent
      fast resistance build-up in the field. Spirodiclofen can be used in alternation
      with most established acaricides, except for other tetronic acid derivatives.
      Without selection pressure, resistance tends to be unstable and can decrease in
      the presence of susceptible individuals owing to the intermediate, polygenic
      inheritance mode.

PMID- 19170252
TI  - Concurrent ART/TB treatment finally proven to be beneficial.
AB  - Giving ART while TB treatment was still ongoing dramatically improved survival
      among HIV/TB-coinfected patients in a large clinical trial in South Africa.

PMID- 19170253
TI  - Munc18: a presynaptic transmitter release site N type (CaV2.2) calcium channel
      interacting protein.
AB  - Munc18 is a presynaptic protein that is essential for transmitter release. Recent
      studies have indicated that this protein is involved in secretory vesicle docking
      but its binding partners in this role remain a mystery. We demonstrate using the
      isolated calyx-type presynaptic terminal of the chick ciliary ganglion that
      staining for Munc18 colocalizes and covaries with that for transmitter release
      site N type calcium channels (CaV2.2), consistent with elements of a common
      release site complex. Biochemical analysis demonstrated that the protein
      coprecipitates with CaV2.2 from lysates of rat or chick brain, including its
      synaptic, long-splice variant; presynaptic terminal surface membrane proteins,
      and a cell line coexpressing Munc18 and CaV2.2. Munc18 bound with high affinity
      to the CaV2.2 II-III intracellular loop, low affinity to the I-II loop but not to
      other channel intracellular regions. Over-expression of Munc18 in dorsal root
      ganglion neurons did not affect CaV2.2 current amplitude or fast kinetics but
      siRNA-knockdown resulted in a negative shift in the steady state inactivation
      curve, an effect attributed to an indirect action via syntaxin 1. Recombinant
      Munc18 also coprecipitated strongly with the v-SNARE synaptotagmin, but only
      weakly with other SNAREs. Thus, the calcium channel may serve as a surface
      membrane platform anchoring a Munc18-containing bridge to synaptotagmin and the
      synaptic vesicle.

PMID- 19170254
TI  - Moving the pH gate of the Kir1.1 inward rectifier channel.
AB  - Both structural and functional studies suggest that pH gating of the inward
      rectifier potassium (K) channel, Kir1.1 (ROMK), is mediated by the convergence of
      four hydrophobic leucines (one from each subunit) near the cytoplasmic bundle
      crossing of the inner transmembrane helices. We tested this hypothesis by moving
      the putative leucine gate from L160-Kir1.1b to other positions along the inner
      transmembrane helix, and measuring inward current and conductance as functions of
      internal pH, using the Xenopus oocyte heterologous expression system. Results of
      these studies indicated that it was possible to replace the putative inward
      rectifier pH gate at L160-Kir1.1b by either a leucine or methionine at 157
      Kir1.1b (G157L-L160G or G157M-L160G). Although both leucine and methionine gated
      the channel at 157-Kir1.1b, residues of similar hydrophobicity (tyrosine and
      valine) did not. Hence, hydrophobicity was a necessary but not a sufficient
      condition for steric gating at 157. This was in contrast to the 160-Kir1.1b
      locus, where side-chain hydrophobicity was both a necessary and sufficient
      property for steric gating. Homology models were constructed for all mutants that
      expressed significant whole-cell currents, using the closed-state coordinates of
      the prokaryotic inward rectifier, KirBac1.1. Models of mutants that retained pH
      gating were too narrow at the bundle crossing to permit hydrated K ion permeation
      in the closed-state. On the other hand, mutants that lost pH gating had ample
      space at the bundle crossing for hydrated K permeation in the closed-state. These
      results support our hypothesis that hydrophobic leucines at the cytoplasmic end
      of the inner transmembrane helices comprise the principal pH gate of Kir1.1, a
      gate that can be relocated from 160-Kir1.1b to 157-Kir1.1b.

PMID- 19170255
TI  - Distribution of the AQP4 water channel in normal human tissues: protein and
      tissue microarrays reveal expression in several new anatomical locations,
      including the prostate gland and seminal vesicles.
AB  - Aquaporins facilitate osmotically driven water movement across cell membranes.
      Aquaporin 4 (AQP4) is a major water channel in the central nervous system where
      it participates in cerebral water balance. AQP4 is also present in basolateral
      membranes of lower respiratory tract airway and renal collecting duct epithelial
      cells, gastric parietal cells and skeletal muscle cells. However, the
      distribution of AQP4 in many other tissues is still unknown. The aim of this
      study was to determine the expression and relative abundance of AQP4 in human
      Tissue MicroArrays (TMAs) and human protein microarrays by immunohistochemistry
      and chemiluminescence. In the central nervous system AQP4 was abundantly
      expressed in the cerebral cortex, cerebellar cortex (purkinje/granular layer),
      ependymal cell layer, hippocampus and spinal cord. Lower levels were detected in
      choroid plexus, white matter and meninges. In the musculoskeletal system AQP4 was
      highly expressed in the sarcolemma of skeletal muscle from the chest and neck. In
      the male genital system AQP4 was moderately expressed in seminiferous tubules,
      seminal vesicles, prostate and epidiymis. In the respiratory system AQP4 was
      moderately expressed in lung and bronchus. AQP expression was abundant in the
      kidney. In the gastrointestinal system AQP4 was moderately present in basolateral
      membranes of parietal cells at the base of gastric glands. AQP4 was also detected
      in salivary glands, adrenals, anterior pituitary, prostate and seminal vesicles.
      Human protein microarrays verified the TMA data. Our findings suggest that AQP4
      is expressed more widely than previously thought in human organs and may be
      involved in prostatic and seminal fluid formation.

PMID- 19170256
TI  - [About correspondence to the Public Service Corporation System].

PMID- 19170257
TI  - Women.

PMID- 19170258
TI  - Land use change and intensification in Papua New Guinea 1975-1996.

PMID- 19170259
TI  - Boserup and Brookfield and the association between population density and
      agricultural intensity in Papua New Guinea.

PMID- 19170260
TI  - Oral health and the aboriginal child: a forum for community members, researchers
      and policy-makers.

PMID- 19170261
TI  - Rural population growth in Papua New Guinea between 1980 and 1990.

PMID- 19170262
TI  - ["Bodily rectitude," or the integration of constraints: the example of the
      corset, an item of clothing creating a body].

PMID- 19170263
TI  - [The body and its fictions. Crossed views: anthropology and history].

PMID- 19170264
TI  - [Influence of research results in medical practice].

PMID- 19170265
TI  - Women as wives, servants and slaves: rethinking the public/private divide.

PMID- 19170266
TI  - Globalization forces and social policy choices: glass half-full or half-empty?

PMID- 19170267
TI  - Policy legacies and the potential for radical surgery on health-care systems.

PMID- 19170268
TI  - [New bisphosphonates and trends in drug therapy for osteoporosis: preface].

PMID- 19170269
TI  - Difficult "transitions" for renal patients.

PMID- 19170270
TI  - Dismantling the Chinese mini-welfare state? Marketization and the politics of
      institutional transformation, 1979-1999.

PMID- 19170271
TI  - The Russian health crisis and the economy.

PMID- 19170272
TI  - One step forward, two steps back: women in the post-Communist states.

PMID- 19170273
TI  - The operation failed, but the patient survived: varying assessments of the Soviet
      Union's last anti-alcohol campaign.

PMID- 19170274
TI  - Youth cultures and consumption in contemporary Europe.

PMID- 19170275
TI  - On the history of the automobile in everyday life.

PMID- 19170276
TI  - The quest for masculinity in a defeated France, 1940-1945.

PMID- 19170277
TI  - Morality and biology in the Spanish Civil War: psychiatrists, revolution and
      women prisoners in Malaga.

PMID- 19170278
TI  - Women's contraceptive practices and sexual behaviour in Europe.
AB  - OBJECTIVES: To assess current and past contraceptive usage, awareness of and
      satisfaction with available methods, and sexual and reproductive behaviour of
      women in 14 European countries (Spain, Italy, UK, France, Germany, Sweden,
      Denmark, Norway, the Czech Republic, Austria, Estonia, Latvia, Lithuania, and the
      Russian Federation). METHODS: A random sample of women aged 15-49 years underwent
      web-based or computer-aided face-to-face interviews in June 2006. All data were
      weighted to correct for differences between the samples surveyed in each country
      relative to their general population, and further weighted relative to the size
      of the overall female population across the participating countries. RESULTS: A
      total of 11,490 women participated in the study. The mean age at first sexual
      intercourse ranged between 16.5 and 18.5 years. The use of contraception at first
      intercourse varied significantly across Europe - the rates were the highest in
      Germany (76%) and France (72%), and the lowest in Russia, the Czech Republic and
      the Baltic States (29-40%). There was considerable heterogeneity in the general
      pattern of current contraceptive usage between countries. Oral contraceptives
      were the most popular current method of contraception, with usage rates highest
      in France (49%) and the Czech Republic (44%) and lowest in Russia, the Baltic
      States and Spain (15-18%). The current absence of contraception was fairly
      consistent across countries, ranging from 21-30%. However, Russia (57%) and the
      Baltic States (50%) had the highest proportion of women using either no
      contraception or 'other methods' (mostly methods considered unreliable).
      CONCLUSIONS: Oral contraceptives remain a popular method of contraception in
      Europe; however, great differences exist in contraception acceptance and in the
      rates of use of the various methods. A sizeable proportion of women do not
      currently use contraception or use contraceptive methods considered to be
      unreliable.

PMID- 19170279
TI  - From the guest editors: how do experts learn?

PMID- 19170280
TI  - Regulator's resurrection. Interview by Alastair McLellan.

PMID- 19170281
TI  - 'Health services should help people lose weight--blaming patients is dangerous'.

PMID- 19170282
TI  - Experts call for urgent improvements in asthma treatment and management.

PMID- 19170283
TI  - Exploring the anatomy and physiology of ageing. Part 11--The skin.

PMID- 19170284
TI  - Nutrition for people with stomas. 2: An overview of dietary advice.
AB  - This two-part unit examines nutrition for people with stomas. Part 1 outlined the
      three types of stomas--colostomy, ileostomy and urostomy--and diet in general.
      This part focuses on postoperative and long-term dietary needs. It includes
      advice on diet related to enhanced recovery and specific to types of stoma.

PMID- 19170285
TI  - Delivering chemotherapy with a nurse-led cancer outreach service.
AB  - This article outlines an initiative to deliver outreach chemotherapy closer to
      patients' homes. Five nurse-led units were set up in the community. Cancer
      treatments can now be provided outside the acute hospital setting. This nurse-led
      service has improved and developed the delivery of chemotherapy by looking at
      alternative and innovative ways of addressing service delivery.

PMID- 19170286
TI  - Hand hygiene compliance: exploring variations in practice between hospitals.
AB  - BACKGROUND: The issue of 'centre' or 'hospital' as an independent variable has
      not been studied extensively in healthcare workers' hand-hygiene practices. AIM:
      To investigate healthcare workers' compliance with hand-hygiene guidelines in
      four acute-care hospitals in Ireland and to examine factors that contributed to
      non-compliance. METHOD: Data collectors observed healthcare workers in four
      hospitals. RESULTS: Data (n = 1,737 observations) was drawn from a random sample
      of nurses, doctors, physiotherapists and HCAs (n = 280 staff). Findings revealed
      that the individual hospital has a significant impact. Multivariate logistic
      regression analysis showed healthcare workers in centre 4 had a significantly
      higher likelihood of non-compliance than those in all other centres (p = 0.003),
      irrespective of gender, discipline or area of work. CONCLUSION: The findings make
      an important contribution to the study of healthcare workers' hand-hygiene
      behaviour and control of healthcare-associated infections. A possible explanation
      of the results may be related to variations in organisational support and
      hospital culture.

PMID- 19170287
TI  - NHS focus shifts to primary care.

PMID- 19170288
TI  - Conflicts.

PMID- 19170289
TI  - Platelet-derived growth factor BB treated osteoprogenitors inhibit bone
      regeneration.
AB  - The study evaluates the ability of osteoprogenitors treated with platelet-derived
      growth factor BB (PDGF-BB) delivered on vinyl styrene microbeads (VSM) to
      regenerate rat calvarial critical-size defects (CSDs). Fetal rat calvarial cells
      were cultured and tested for their ability to attach to VSM using scanning
      electron microscopy. Twenty-five rats were equally divided into 5 groups; a
      negative control (GPI), vinyl styrene microbeads (GPII), PDGF-BB (GPIII), VSM
      plus osteoblastic progenitors (GPIV), and VSM plus PDGF-BB treated osteoblastic
      progenitors (GPV). CSDs were created and reconstructed according to the mentioned
      study design. After 16 weeks, animals were sacrificed and defect areas evaluated
      for bone regeneration. Cells attached to the microbeads; however, their
      morphology and topography were affected by the PDGF-BB. Transplanting the
      VSM/cells constructs to CSDs revealed significant reduction of bone regeneration
      upon pretreatment of the cells with PDGF-BB. However, short-term application of
      PDGF-BB to CSD stimulated bone regeneration. The ability of osteoprogenitor cells
      to regenerate bone was significantly reduced upon pretreatment with PDGF-BB in
      vitro. However, adding PDGF-BB at the time of surgery had stimulated bone
      regeneration.

PMID- 19170290
TI  - Finite element analysis of stress in bone adjacent to dental implants.
AB  - Understanding how clinical variables affect stress distribution facilitates
      optimal prosthesis design and fabrication and may lead to a decrease in
      mechanical failures as well as improve implant longevity. In this study, the many
      clinical variations present in an implant-supported prosthesis were analyzed by a
      3-dimensional finite-element method. The anterior segment of a human mandible
      treated with 5 implants supporting a curved beam was created to perform the
      tests. The variables introduced in the computer model were cantilever length,
      elastic modulus of cancellous bone, abutment length, implant length, and
      framework alloy (AgPd or CoCr). The computer was programmed with physical
      properties of the materials as derived from the literature, and a 100-N vertical
      load was used to simulate the occlusal force. Images with fringes of stress were
      obtained, and the maximum stress at each site was plotted in graphs for
      comparison. Stresses tended to be concentrated at the cortical bone around the
      neck of the implant closest to the load, whereas stresses in cancellous bone were
      considered low. In general, the stress distribution was better with stiffer
      cancellous bone, longer abutments and implants, and shorter cantilevers. The use
      of a CoCr alloy framework appears to contribute to a better stress distribution.

PMID- 19170291
TI  - A comparison of facial and lingual cortical thicknesses in edentulous maxillary
      and mandibular sites measured on computerized tomograms.
AB  - Edentulous ridges suitable for implant treatment depend on cortical bone for
      implant stability, especially for ridge-expansion procedures. This study was done
      to find and compare the actual thicknesses of the facial and lingual edentulous
      cortices of the maxilla and mandible as measured on computerized tomograms. The
      collected computerized tomographs (CT) of one implantologist's practice (D.F.)
      were measured. The measurements taken demonstrated that the edentulous lingual
      cortex is almost always thicker than the facial cortex in the maxilla and
      mandible. The combined maxillary and mandibular facial cortices measurement sites
      average was 1.79 mm. The combined maxillary and mandibular lingual cortices
      measurement sites average was 2.33 mm. The average cortical thickness measurement
      of the maxillary facial cortices was 1.66 mm. The lingual maxillary average was
      2.16 mm. The mandibular facial cortical sites averaged 1.83 mm, while the lingual
      cortical sites were 2.40 mm. These data confirm that the lingual cortex of the
      maxilla and mandible is thicker than the facial cortex at a ratio of 1:1.3. This
      ratio was consistent for maxilla and mandible.

PMID- 19170292
TI  - Immediate load and esthetic zone considerations to replace maxillary incisor
      teeth using a new zirconia implant abutment in the bone grafted anterior maxilla.
AB  - The goal of this prospective clinical study is to evaluate a new all-ceramic
      implant abutment made from zirconium oxide during the immediate load of dental
      implants placed in the block grafted anterior maxilla. This new zirconia abutment
      gives the clinician the opportunity to provide the patient with an all-ceramic
      restorative system (abutment and crown) for an optimum esthetic result and a high
      level of patient satisfaction. A total of 9 hydroxyapatite-coated dental implants
      were surgically placed in 9 patients and were immediately loaded 5 to 7 days
      later with a custom composite provisional restoration that was placed out of
      functional occlusion. Each prefabricated, natural colored zirconia abutment was
      shaped and connected to the implant with a titanium screw. Provisional
      restorations were cemented to the zirconia abutment with the use of temporary
      cement. Twelve weeks later, the provisional restoration was replaced with an all
      ceramic restoration. Over a 52-week observation period, no abutment fractures
      occurred, and no abutment screw loosening was observed. No implants failed. All 9
      patients reported total satisfaction regarding esthetic quality of the all
      ceramic restorative system (abutment and implant). Preliminary results of this
      clinical study indicate that this new zirconia abutment offers the clinician and
      the patient exceptional strength, optimal esthetics, and simplicity. It is of
      important clinical significance that use of this all-ceramic abutment eliminates
      the well-known disadvantages of metal abutments.

PMID- 19170293
TI  - Peri-implant diseases may be associated with increased time loading and
      generalized periodontal bone loss: preliminary results.
AB  - The aim of this study was to evaluate the prevalence of peri-implant diseases
      around Branemark system implants in Brazilians and the possible relationship with
      periodontal bone loss, systemic condition, and demographic profile. A total of
      113 individuals were enrolled in this study, and they received 347 implants. The
      implants were clinically and radiographically examined and diagnosed as healthy
      implants, mucositis, or peri-implantitis. The demographic and systemic profiles
      of the individuals were assessed via questionnaires, and the time of loading was
      obtained from files. The presence of periodontal bone loss in partially
      edentulous patients was determined by standardized radiographic evaluation. With
      regard to implants, the prevalence was 60.5% (n = 210), 32% (n = 111), and 7.5%
      (n = 26) for healthy tissues, mucositis, and peri-implantitis, respectively. No
      correlation was found between peri-implant tissue conditions and socioeconomic
      status, body mass index, smoking status, gender, age, diabetes mellitus,
      osteopenia, and osteoporosis. Statistically significant positive correlations
      were found in implants with mucositis and peri-implantitis in relation to time of
      loading and with peri-implantitis in relation to periodontal bone loss in the 4
      quadrants (P < .05). Presence of peri-implant diseases may be associated with the
      increasing time of loading and generalized periodontal bone loss.

PMID- 19170294
TI  - A new tunnel technique with acellular dermal matrix for soft tissue preparation
      prior to symphyseal block graft--a description of technique and case report.
AB  - The aim of this report was to describe a newly designed tunnel technique (A New
      Tunnel Technique) using acellular dermal matrix (ADM) allograft for soft tissue
      augmentation prior to mono-cortical block graft. Two cases with vertical and
      horizontal ridge deficiency in the mandibular anterior area were indicated for
      mono-cortical block grafting before implant placement. Soft tissue evaluation and
      measurements showed thin tissue covering the defect area composed mainly of
      nonkeratinized alveolar mucosa measuring 1 to 2 mm in most of the sites. Soft
      tissue augmentation was done first using a new tunnel technique with ADM
      allograft. After 2 months of healing, mono-cortical block graft was harvested
      from the mandibular symphysis area and fixed to the recipient site. Soft tissue
      measurements were made before soft tissue graft and immediately before block
      graft. Healing was evaluated at 2, 4, 12, and 24 weeks post-block grafting
      surgery to evaluate healing. In both cases, there was generalized 1- to 2-mm
      increase in soft tissue thickness covering the defect areas following allograft.
      Both cases had healed uneventfully with no soft tissue complications following
      block grafting procedure to the time of implant placement. The new tunnel
      technique for soft tissue augmentation using acellular dermal matrix allograft
      seems to be a valid approach in soft tissue preparation prior to mono-cortical
      block grafting. Further research is needed to evaluate if this procedure will
      help to prevent soft tissue complications associated with block grafting.

PMID- 19170295
TI  - Success rate of the EVL evolution implants (SERF): a five-year longitudinal
      multicenter study.
AB  - The purpose of this study was to evaluate the success rate of the SERF EVL
      evolution implants (Decines, France) through a 5-year longitudinal multicentric
      study. Patients from 3 clinicians working in 3 different private practices
      (Grenoble, Nice, and Paris) and familiar with this implant system were included
      in this study; 413 patients and 1198 implants were followed over 5 years. The
      implant sites and implant types were recorded at the time of placement. The
      patients were followed yearly and controlled at the end of the study. The
      criterion for treatment evaluation or success was a qualitative variable related
      to 4 possible treatment outcomes: success, failure, ailing, and lost (dropout
      patients). Different variables (sex, bone quantity and quality at the implant
      site, location) were submitted to the chi-square test. A survival curve was
      established over 5 years according to the Kaplan Meyer method. The clinical
      follow-up was 3.1 +/- 1.2 years (ie, 1 to 6 years). At the end of this follow-up
      period, 1163 implants were classified as successful, 19 as failures, 12 as
      ailing, and 4 as lost (dropout). This implant system thus presented an overall
      success rate of 97.08%, over 5 years, independent of implant location, and for
      patient indications commonly encountered in private practice.

PMID- 19170296
TI  - Gifts.

PMID- 19170297
TI  - Neuroscience nursing: where do we go from here?

PMID- 19170298
TI  - Chronic unilateral neglect from focal meningoencephalitis lesions in an immune
      compromised hemodialysis patient.
AB  - Unilateral neglect (UN) is a disorder associated primarily with right-brain
      damage; it causes individuals to behave as if the contralesional half of their
      world has become unimportant or has simply ceased to exist. This is the first
      known case study to describe and measure UN caused by an infectious process,
      meningoencephalitis. The patient was immune compromised as a result of
      antirejection drugs following a kidney and pancreas transplant, as well as from a
      baseline vulnerability common to patients with hemodialysis. She was reassessed
      serially during hemodialysis treatments over 12 months and demonstrated
      improvement in some measures of UN but not in others. UN is a recognized nursing
      diagnosis and can be assessed, treated, and researched by nurses. Neuroscience
      nurses need to better understand and investigate UN to improve their own practice
      and the practice of other specialties.

PMID- 19170299
TI  - Factors that influence health-seeking behaviors of patients experiencing acute
      stroke.
AB  - Stroke is the third leading cause of death in the United States and the leading
      cause of serious, long-term disability. Patients who sustain a sudden ischemic
      stroke can benefit from the administration of intravenous recombinant tissue
      plasminogen activator (rt-PA). rt-PA may reduce disability, yet few patients
      arrive in emergency departments in time to be eligible for rt-PA administration.
      The purpose of this study was to discover factors that influence patients'
      decision-making process when seeking treatment for acute-stroke symptoms.
      Qualitative inquiry using grounded-theory methods was used to elicit descriptions
      of the decision-making process. The primary purpose of grounded theory is to
      generate explanatory models of human behavior that are grounded in the data. A
      purposive sample of 10 clinically stable patients or their caregivers were
      interviewed after acute ischemic stroke. Data were analyzed and broken down into
      descriptive themes following the grounded-theory approach. Distinct themes
      emerged for patients who presented for treatment early and late. Five themes
      emerged for patients who presented late for treatment: lack of knowledge, fear of
      hospitals, denial, living alone, and preexisting health concerns. The theme that
      emerged from the group that presented early for treatment was previous history or
      knowledge of stroke. The most significant implication for practice identified in
      this study is that nurses must take a leading role in educating the public
      regarding symptoms, risk factors, and available treatments for stroke.

PMID- 19170300
TI  - Patient and physician attitudes regarding clinical trials in neurofibromatosis 1.
AB  - Neurofibromatosis 1 (NF1) is a multisystem genetic disorder that primarily
      affects the skin (freckling and cafe-au-lait macules), nervous system
      (neurofibromas, optic gliomas, and learning disabilities), and skeletal system
      (pseudoarthroses). The interest in pharmacological intervention for patients with
      NF1 has grown in recent years. However, little is known about the attitudes and
      priorities of patients, families, and physicians regarding participation in
      clinical trials. We surveyed 74 adult patients or parents of patients with NF1
      and 69 care providers participating in a neurofibromatosis clinic to assess their
      willingness to participate in clinical trials and their opinions about which
      conditions they thought were most important to treat. Both patients and care
      providers are willing to participate in clinical trials for NF1 and both groups
      rate malignant peripheral nerve sheath tumors as the most urgent for new
      treatments. There are concordant views among patients and physicians concerning
      clinical trials for NF1, and patients do not dismiss participation in placebo
      controlled trials. Neuroscience nurses are poised to facilitate the research
      process from conception through implementation as they take the viewpoints of our
      study populations into consideration.

PMID- 19170301
TI  - Ethical decision making in neurosurgery: a case study.
AB  - Neurosurgical patients often challenge their caregivers with moral issues that
      arise during their care. As the population ages, end-of-life decision making and
      flexible planning need to be stressed so patients can be included in their care
      decisions and better communicate with the healthcare team. This case study
      illustrates how one team of nurses used an ethical decision-making model and a
      caring perspective to help a patient successfully navigate a complex healthcare
      system as they advocated for her increased involvement in her care.

PMID- 19170302
TI  - A prospective baseline versus on-treatment study assessing patient perceptions of
      using a smaller needle when injecting intramuscular interferon beta-1 a (Avonex).
AB  - This study assessed patient perceptions of using a smaller needle (1-inch, 25
      gauge) to administer weekly intramuscular (IM) interferon beta-1 a (IFNbeta-1 a
      [Avonex]) injections. Patients received 1 IM IFNbeta-1 a injection at baseline
      using the standard needle (1.25-inch, 23-gauge), followed by 4 weekly injections
      using the smaller needle. The primary end points were change in self-reported
      visual analog scale scores for preinjection anxiety and postinjection pain,
      assessed at baseline and once weekly during the 4 weeks of therapy with the
      smaller needle. Secondary evaluations included assessment of patient perception
      of ease of use and fear of self-injection with 2 questionnaires, and changes in
      the number of injection-site reactions. Patients had a mean decrease of 25 +/- 31
      mm (baseline mean, 46 mm; 4-week mean, 21 mm; p = .0002) in anxiety score and a
      mean decrease of 22 +/- 29 mm (baseline mean, 41 mm; 4-week mean, 19 mm; p =
      .0003) in pain score. Overall, patients thought the smaller needle was easier to
      use than the standard needle. Qualitative measurements suggested patients who
      self-injected IM IFNbeta-1 a experienced less fear when using the smaller needle.
      Preinjection preparation parameters decreased throughout the course of the
      treatment period. No patients experienced injection-site reactions with the
      smaller needle. Patients preferred using a smaller needle to administer their
      weekly IM IFNbeta-1 a injection.

PMID- 19170303
TI  - Early interferon beta treatment in multiple sclerosis: nursing care implications
      of the BENEFIT study.
AB  - Interferon beta (IFNbeta) is a first-line treatment for relapsing forms of
      multiple sclerosis (MS) that can reduce the rate of clinical attacks and limit
      disability progression. Recent trials have shown that initiating IFNbeta
      treatment at the time of the first clinical event suggesting MS can delay the
      onset of clinically definite MS and, in the case of IFNbeta-1 b, inhibit the
      progression of later disability. These findings have led to a trend toward
      earlier treatment initiation in clinical practice. While trials show good levels
      of adherence to therapy, there often is room for improvement in the clinical
      setting. Managing MS symptoms and treatment-related adverse events and providing
      patient education are vital to optimize adherence, and nurses can employ a number
      of strategies as part of the support program to ensure patients gain the most
      benefit from their treatment. In addition to providing a great deal of evidence
      supporting early MS treatment, the ongoing BEtaseron in Newly Emerging multiple
      sclerosis For Initial Treatment (BENEFIT) study has highlighted the fact that
      IFNbeta can be well tolerated, especially with correct management. This article
      summarizes the lessons learned from the BENEFIT study, and the ways in which
      nurses can incorporate this knowledge into clinical practice.

PMID- 19170304
TI  - Challenging the gold standard: should mannitol remain our first-line defense
      against intracranial hypertension?
AB  - Mannitol has long been the "gold standard" for treatment of cerebral edema and
      refractory intracranial hypertension in traumatic brain injury, subarachnoid
      hemorrhage, and stroke. Studies performed in animals have shown that hypertonic
      saline (HS), in doses ranging from 3% to 10%, may be more effective than mannitol
      in treating these populations. Recently, randomized clinical trials have
      evaluated the efficacy and safety of HS versus mannitol in the treatment of
      elevated intracranial pressure (ICP). This research has been prompted by mounting
      concern about the side effects of mannitol, the limited ability to give multiple
      doses of the drug, and an increased understanding of cerebral physiology. Four
      studies have compared the use of HS and mannitol in brain-injured populations.
      These studies have shown that not only is HS a safe drug (no patients experienced
      adverse effects), it is also more efficient in reducing ICP. Efficiency is
      defined as the drug's ability to decrease ICP to acceptable levels and to
      maintain lower ICPs for a longer duration of time. It is important for nurses who
      administer osmotic diuretics to evaluate and understand the current research to
      provide educated and appropriate care.

PMID- 19170306
TI  - What is evidence-based neuroscience nursing practice?

PMID- 19170305
TI  - Why are reliability and validity important to neuroscience nurses?

PMID- 19170307
TI  - Medical notes.

PMID- 19170308
TI  - One man's poison ... [is another's unfurrowed brow].

PMID- 19170309
TI  - Anthropological perspectives on medicine: introduction.

PMID- 19170310
TI  - Towards cultural humility in healthcare for culturally diverse Rhode Island.
AB  - This article presents a framework for quality care that attends to culture and
      ethnicity. Tools and approaches for achieving cultural competency and humility
      are provided that may help improve the care of the patients, irrespective of
      their backgrounds or beliefs.

PMID- 19170311
TI  - Negotiating clinically workable solutions across cultures: lessons learned.

PMID- 19170312
TI  - Cultural bias and 'no-scalpel vasectomies': lessons learned by a Brown
      anthropologist in Mexico.

PMID- 19170313
TI  - Overweight and diabetes in American Samoa: the cultural translation of research
      into health care practice.

PMID- 19170314
TI  - Evaluating geriatrics in the medical school curriculum: using student journals.

PMID- 19170315
TI  - The practicing physicians' guide to pressure ulcers in 2008.

PMID- 19170316
TI  - Evaluation of case management services for lead poisoned children in Rhode
      Island.

PMID- 19170317
TI  - The quadrivalent human papillomavirus vaccine.

PMID- 19170318
TI  - Electronic medical records.

PMID- 19170319
TI  - Lyme disease.

PMID- 19170320
TI  - A purgatory of ambiguous words.

PMID- 19170321
TI  - Mastering the art of politics.
AB  - As a long-term political relationship matures, the nurse's scope of influence
      with the legislator generally grows and mutual respect ensues. In the best
      relationships, legislators seek the opinion of nurses on health care questions
      and ask them to share their expertise at informal meetings or through formal
      testimony at a policy committee hearing. When possible, backing friendly
      legislators from either party during their re-election bids places nurses in a
      proactive rather than a reactive relationship with legislative policymakers.
      Alliances-are further developed when nursing organizations endorse legislators
      who have taken pro-nursing stances on important issues. Nurses or nursing groups
      that take the initial step toward involvement in the political process are the
      ones who will influence the future of nursing and health care policy. Visionary
      nurses throughout the past century helped establish nursing as a professional
      discipline. They were risk takers with a dream and acted for the betterment of
      nursing. We should still heed the advice of one of these prominent visionaries,
      Florence Nightingale, who said: The progressive world is necessarily divided into
      two classes--those who take the best of what there is and enjoy it--those who
      wish for something better and try to create it. Without these two classes, the
      world would be badly off. They are the very conditions of progress, both the one
      and the other. Were there none who were discontented with what they have, the
      world would never reach anything better (Nightingale, 1860/1979, p. 29). You need
      to seize the moment, be risk-takers, become politically-savvy nurses and make a
      difference in the profession of nursing and, more importantly, the lives of the
      patients who are entrusted to your care!

PMID- 19170322
TI  - An advocacy work group: impacting legislative, regulatory, and professional
      practice issues.

PMID- 19170323
TI  - Those who served: nurse members in the PA House of Representatives.

PMID- 19170324
TI  - Act 52 of 2007: the Authority's role, progress to date, and future goals.

PMID- 19170325
TI  - Protecting your nursing license: an overview of the complaint and disciplinary
      process of the Bureau of Professional and Occupational Affairs.

PMID- 19170326
TI  - Pennsylvania access to basic care plan should be a priority.

PMID- 19170327
TI  - Our bodies and the legacy of "better living through chemistry".

PMID- 19170328
TI  - Doctors' unique perspective.

PMID- 19170329
TI  - Count the spaces!

PMID- 19170330
TI  - Voices of reason. AMS requests encouragement, participation during 87th
      Legislative Session.

PMID- 19170331
TI  - Well child and EPSDT screening: strategies for improvement.

PMID- 19170332
TI  - Unusual pathogens in Arkansas: Enterobacter sakazakii.

PMID- 19170333
TI  - Patent foramen ovale.
AB  - A 42-year-old white man with good exercise tolerance comes in for a follow-up
      appointment. He had a transthoracic echocardiogram (TTE) to evaluate an apical
      systolic murmur heard on routine physical examination. TTE shows mild to moderate
      mitral regurgitation with normal function. A slightly enlarged right atrial and
      ventricular cavity size prompted a micro-cavitation study which is positive for
      an intracardiac shunt.

PMID- 19170334
TI  - CH medical home program for special needs children. A new medical era...
AB  - The ACH Medical Home Program serves as a comprehensive, multi-discipline clinic
      and program designed to facilitate comprehensive, coordinated care to the most
      medically complex and fragile children in Arkansas. In partnership with the
      family, the PCP and the subspecialty physicians, the program strives to ensure
      that the ideals of providing the "medical home" are accomplished, both in the
      community and at Arkansas Children's Hospital. An ongoing evaluation process has
      been implemented and it is the hope and mission of this program to evolve to
      provide the highest quality of care and highest quality of life for these
      children with complex medical conditions and for their families. Referrals and
      inquiries are welcomed and encouraged and can be made at (501) 364-3030.

PMID- 19170335
TI  - [The foot and mouth disease outbreak 6 years later: consequences for
      veterinarians].
AB  - The consequences of the outbreak of foot-and-mouth disease in 2001 in The
      Netherlands can still be noticed in the daily work of the veterinarians involved.
      In particular, the number off arm animals has decreased, regulations have
      changed, and cattle farmers have become more confrontational. While the
      psychosocial consequences to veterinarians of the outbreak have decreased
      compared with immediately after the outbreak, this decrease is not statistically
      significant. Moreover, 40% of the veterinarians involved still show signs of a
      traumatic stress reaction. Should another outbreak occur, it is important that
      local veterinarians are contacted, in order to improve communication with cattle
      farmers.

PMID- 19170336
TI  - [Recent developments in domestic animal anesthesia].

PMID- 19170337
TI  - [Methicillin resistance Staphylococcus aureus in the horse clinic].

PMID- 19170338
TI  - [Licensed practitioner or competent?].

PMID- 19170339
TI  - [Back to Karuna].

PMID- 19170340
TI  - [Responsible use of veterinary drugs by pig farmers].

PMID- 19170341
TI  - [African swine fever: also a threat for Holland?].

PMID- 19170342
TI  - [Dissertation Dik Mevius].

PMID- 19170343
TI  - [Survey socioeconomic position of veterinarians 2008 part I: work load and
      income].

PMID- 19170344
TI  - [The veterinarian in 2015].

PMID- 19170345
TI  - [Letter: veterinarian loses his profession].

PMID- 19170346
TI  - [Symposium "Everyday zoonoses"].

PMID- 19170347
TI  - [GGL-congress 2008: 'big-bigger-biggest'].

PMID- 19170348
TI  - [Column GGL: animal husbandry a danger for our health?].

PMID- 19170349
TI  - The future of internal medicine in Belgium.

PMID- 19170350
TI  - Duty hours restriction: sleeping with the enemy?

PMID- 19170351
TI  - Restriction of duty hours for residents in internal medicine: a question of
      quality of life but what about education and patient safety?
AB  - Like in other medical specialities, training in internal medicine is confronted
      with the duty hours regulation. A reduction to a maximum of 48 duty hours has
      been introduced in Belgium in 1999 for all residents and is still under debate in
      the European Communities. A reduction of duty hours to a maximum of 80 hours per
      week was recently adopted in the USA. Several surveys were conducted in this
      country before and after the introduction of the new system to evaluate its
      impact on training and patient care. A reduction of duty hours appears to improve
      the mental health and the security and the quality of life of the trainees. On
      the other hand, it is suspected that reducing training hours can have a negative
      effect not only on education but also on patient safety and satisfaction giving
      the fragmentation of care. This appears to be a key problem, particularly in
      internal medicine, as it implies more frequent transfers of medical information,
      a source of medical errors and a loss of responsibility.

PMID- 19170352
TI  - Spectrum and workload of consultation activities in a Belgian tertiary paediatric
      cardiac centre.
AB  - BACKGROUND: Few data are available on the spectrum and frequency of issues
      addressed in the paediatric cardiology consultation service of tertiary academic
      hospitals. METHODS: Those activities were collected prospectively during 6
      months. RESULTS: A total of 967 consultations were performed. The origin was
      mostly the medical ward (n = 535), the intensive care unit (n = 195), the
      neonatal unit (n = 97), the operating room (n = 84) and the nursery (n = 44). In
      553 cases, a heart disease was previously known and the most common reasons of
      consultation were postoperative (n = 279) and preoperative evaluations (n = 129).
      Thirteen newborns had a prenatal suspicion of congenital heart disease, which was
      confirmed in 11 cases. For the other 401 consultations, the most common clinical
      concerns included cardiac function in oncological disease (n = 60), murmur (n =
      48), syncope (n = 33), diabetes mellitus (n = 28), prematurity (n = 27), syndrome
      (n = 19), unexplained stridor or respiratory distress (n = 19) and unexplained
      fever (n = 15). There were new diagnoses of congenital heart disease, acquired
      heart disease and arrhythmias in 35, 17 and 5 cases, respectively. CONCLUSIONS:
      The workload of the paediatric cardiology consultation service is increasing
      alarmingly. These data may be helpful in future planning of consultant manpower
      and in curriculum development in cardiac training of students and residents.

PMID- 19170353
TI  - Impact of postures on blood pressure in healthy subjects.
AB  - BACKGROUND: Controversies exist on the nature of influence of body position on
      the level of blood pressure. This study was designed to investigate the impact of
      postures on blood pressures in healthy subjects. METHODS: Blood pressure was
      measured in 6,485 healthy subjects in both supine and sitting positions, using a
      standard mercury sphygmomanometer. RESULTS: The average systolic and diastolic
      blood pressure in all age groups in the supine position was higher than in the
      sitting position (P < 0.001). There was a reduced systolic pressure increment but
      enhanced diastolic pressure increment with aging (P < 0.05). The levels of
      sitting blood pressure were inversely correlated to the pressure increments in
      supine positions (P < 0.001). Multivariate regression analysis showed that age is
      an independent factor for the systolic pressure increment in the supine position
      (P < 0.001), whereas sex, age, body height and body mass index are independent
      predictors for the increment in diastolic blood pressure (P < 0.001).
      CONCLUSIONS: In healthy subjects, blood pressure in the supine position is higher
      than in the sitting position and age plays an important part in this posture
      related pressure increment.

PMID- 19170354
TI  - Guidelines for the use of fresh frozen plasma.
AB  - Recommendations, which aim at standardising and rationalising clinical
      indications for the transfusion of fresh frozen plasma (FFP) in Belgium, were
      drawn up by a working group of the Superior Health Council. For this purpose the
      Superior Health Council organised an expert meeting devoted to "Transfusion
      Guidelines: Pathogen reduction, products and indications for the transfusion of
      plasma" in collaboration with the Belgian Haematological Society.The experts
      discussed the indications for the transfusion of FFP, pathogen reduction for FFP
      and the practical issues of administering FFP and plasma-derived concentrates.
      The recommendations formulated by the experts were validated by the working group
      with the purpose of harmonising FFP transfusion in Belgian hospitals.

PMID- 19170355
TI  - Simultaneous occurrence of metastatic breast cancer, Hodgkin's disease and
      tuberculous lymphadenitis in homolateral axillary lymph nodes--a case report.
AB  - We report the case of a 78-year-old woman, presenting with enlarged axillary
      lymph nodes. Histological analysis of the lymph nodes demonstrated the co
      existence of locally advanced breast carcinoma, scleronodular Hodgkin's disease
      and tuberculous lymphadenitis.The association of the 3 disorders in the same
      lymphatic region is unreported so far.

PMID- 19170356
TI  - Ecthyma gangrenosum in a non-neutropaenic, elderly patient: case report and
      review of the literature.
AB  - Ecthyma gangrenosum is a cutaneous infection most commonly associated with
      Pseudomonas aeruginosa bacteraemia, but it may also be encountered after
      breakdown of mechanical defence barriers and local infection. The characteristic
      lesions of ecthyma gangrenosum are haemorrhagic blisters with surrounding
      erythema that rapidly evolve to necrotic ulcers. A high mortality rate is
      reported, especially when diagnosis is delayed and in the absence of appropriate
      therapy. Ecthyma gangrenosum usually occurs in critically ill and
      immunocompromised patients. Haematological malignancies and neutropaenia are the
      major risk factors, but other comorbidities (e.g. diabetes mellitus and
      malnutrition) have also been involved. Here, we report a case of ecthyma
      gangrenosum in a non-neutropaenic elderly patient with multiple comorbidities and
      review the literature on ecthyma gangrenosum.

PMID- 19170357
TI  - Pelvic inflammatory disease due to Streptococcus pneumoniae: a usual pathogen at
      an unusual place.
AB  - We report three cases of pelvic inflammatory disease (PID) due to Streptococcus
      pneumoniae in previously healthy young women. S. pneumoniae frequently causes
      bacteremia, meningitis and respiratory infections, but it very rarely infects the
      genital tract. All our patients presented with an acute onset of severe abdominal
      pain and had an intrauterine device (IUD) present. No abnormal sexual behavior
      was noticed. Although the relation between PID due to S. pneumoniae and the use
      of an IUD has been a topic for discussions, culture of IUD in all our patients
      and blood culture in 2 of 3 of our patients revealed S. pneumoniae. All patients
      recovered well with intravenous antibiotic treatment and removal of the IUD.

PMID- 19170358
TI  - New therapeutic approaches in type 2 diabetes.
AB  - Type 2 diabetes is a progressive chronic disease resulting from a dynamic
      interaction between defects in insulin secretion and insulin action. New
      molecules have recently been launched and many others are under clinical
      investigation. Besides classical sulfonylureas and glinides, new insulin
      secretagogues are now available, which target the incretin gut hormone glucagon
      like peptide-1 (GLP-1). Indeed, oral incretin enhancers acting as antagonists of
      the enzyme DPP-4 (dipeptidylpeptidase-4), which inactivates natural GLP-1,and
      injectable incretin mimetics (exenatide) or analogues (liraglutide), which
      reproduce the actions of GLP-1 while resisting to DPP-4, represent new
      opportunities to stimulate insulin secretion, without increasing the risk of
      hypoglycaemia and weight gain. Among insulin sensitizers, metformin remains
      unequivocally the first drug of choice for the treatment of type 2 diabetes,
      whereas promising drugs as thiazolidinediones (glitazones) were recently
      challenged because of various safety issues. When insulin is required, insulin
      analogues, both short-acting and basal ones, may offer some advantages regarding
      better control of postprandial hyperglycaemia, reduced risk of hypoglycaemia
      and/or lower weight gain in patients with type 2 diabetes. Emphasis should be put
      on early detection and intensive management of type 2 diabetes, individualized
      glucose lowering treatments and goals, stepwise pharmacological strategy avoiding
      therapeutic inertia, and multiple cardiovascular risk--targeted approach.

PMID- 19170359
TI  - Up-to-date in pulmonary and extrapulmonary sarcoidosis.
AB  - Sarcoidosis is a multisystemic immune disorder of unknown cause characterized by
      the formation of epithelioid granuloma in involved organs particularly the lung
      and the lymphatic system. Consistent recent advances have been made on the
      clinical, therapeutical and pathogenetic aspects. CLINICAL ASPECTS: Various
      clinical phenotypes are better characterized and efforts to grade the severity
      could facilitate genetic studies and therapeutic trials. Pulmonary hypertension
      and some infrequent or atypical pulmonary manifestations as well as some rare
      extrapulmonary localizations have been thoroughly studied. Sarcoidosis-like
      granulomatosis due to identified causes constitute interesting models and have to
      be differentiated from sarcoidosis. THERAPEUTICAL ASPECTS: Anti-TNFalpha drugs
      have been investigated and infliximab has been proved efficient even though some
      limits to its efficiency have to be taken into account. PATHOGENETIC ASPECTS:
      Finally, advances concerning the pathogenesis, particularly genetic predisposing
      factors and phenotype/genotype correlations have been made.

PMID- 19170360
TI  - Infective endocarditis.
AB  - The diagnosis of infective endocarditis remains difficult. The complication rate
      is very high. Serious complications may occur and the overall mortality is still
      20-25%. The sooner the treatment is started, the better the final result.
      Antibiotic therapy is essential but cardiac surgery is frequently necessary.
      Early surgery improves outcome. A multidisciplinary approach by internal
      medicine, cardiology and cardiac surgery facilitates the efficiency of diagnosis
      and treatment.

PMID- 19170361
TI  - Update on the treatment of pituitary adenomas: familial and genetic
      considerations.
AB  - Clinically-relevant pituitary adenomas occur with a prevalence of approximately 1
      per 1000 population in Belgium. Pituitary adenomas that occur in families are
      likely to have an important genetic pathophysiological basis. Currently about 5%
      of all pituitary adenoma cases have a family history of pituitary adenomas,
      classically due to multiple endocrine neoplasia type 1 (MEN1) and Carney complex
      (CNC). Over the last decade we have described non-MEN1/CNC familial pituitary
      tumours that include all tumour phenotypes, a condition named 'familial isolated
      pituitary adenoma' (FIPA). Clinical features of FIPA differ from those of
      sporadic pituitary adenomas in that patients with FIPA are often younger and have
      larger tumours at diagnosis. Approximately 15% of FIPA patients have mutations in
      the aryl hydrocarbon receptor interacting protein gene (AIP), which indicates
      that FIPA may have a diverse genetic pathophysiology. In this review we examine
      new findings on the epidemiology of pituitary adenomas and we review familial
      causes of pituitary adenomas with a particular emphasis on modern clinical
      testing. In addition, the clinical and genetic features of FIPA are described as
      FIPA represents a useful framework to study the features of pituitary adenomas
      that occur in a familial setting.

PMID- 19170362
TI  - Penetrating atherosclerotic ulcer of the aorta.

PMID- 19170363
TI  - Chemotherapy-induced diffuse melanonychia.

PMID- 19170364
TI  - An evidence-based dentistry challenge: treating patients on warfarin (Coumadin).

PMID- 19170365
TI  - [Dilemma of the results interpretation of molecular genetic analysis with a focus
      on CFTR gene mutations in men with reproductive disorders and in gamete donors].
AB  - OBJECTIVE: The presentation of the results of molecular genetics analysis in men
      with reproductive disorders and in gamete donors with a focus on interpretation
      of the results CFTR gene analysis. DESIGN: Original article. SETTING: Institute
      of Biology and Medical Genetics of the First Faculty of Medicine and General
      Teaching Hospital. METHODS: We examined 164 men with reproductive disorders for
      36 selected mutations in CFTR gene including T(n) polymorphism and for Y
      chromosome microdeletions. As well we examined mutations in CFTR gene including
      T(n) polymorphism in 104 gamete donors. RESULTS: We detected microdeletions in
      AZF region in 3 cases of affected men and in other 3 casses we found mutation
      F508del (heterozygotes) in CFTR gene with T5 variant in trans position. Except
      this we detected in 5 affected men "only" heterozygous mutations in CFTR gene and
      in 12 men "only" the T5 variant in heterozygous level. Among gamete donors we
      found 3 heterozygotes for mutation F508del and 11 heterozygotes for T5 variant.
      CONCLUSION: In infertile men and in gamete donors we recommend to examine not
      only the "classical" mutations in CFTR gene but also the relatively frequent T5
      variant, which can be in certain conditions considered as a pathogenic mutation.
      It's necessary to rule out the carriers of T5 variation from gamete donors.

PMID- 19170366
TI  - [Fetal thymic involution on ultrasound].
AB  - OBJECTIVE: The purpose of this study was to summarize the published data on the
      fetal thymus, the fetal thymic involution and the possible use of the measurement
      of the fetal thymus in the clinical practice. DESIGN: Review. SETTING: Department
      of Obstetrics and Gynecology Medical Faculty Charles University Hradec Kralove.
      METHODS: We summarized published data on the fetal thymic involution and
      relationship between the sonographic fetal thymus size and the presence of an
      intrauterinne infection in patiens with preterm labor or preterm prelabour
      rupture of membranes. CONCLUSION: The present review summarizes the results of
      clinical and experimental research on the fetal thymic involution.

PMID- 19170367
TI  - [Birth defects in the Czech Republic in 2006].
AB  - AIM OF STUDY: An analysis of occurrence of selected birth defects in the Czech
      Republic in 2006. Comparison of mean incidences of selected birth defects during
      the 1994-2006 to previous period data. TYPE OF STUDY: Retrospective
      epidemiological analysis of birth defects incidences from the Czech National
      Birth Defects Register database. MATERIAL AND METHODS: Data from the National
      Birth Defects Register (Institute for Health Information and Statistics) in the
      Czech Republic in the 1994-2006 period were used along with data on prenatally
      diagnosed and terminated pregnancies from the same period. Mean incidences of
      selected types of defects (anencephaly, spina bifida, encephalocele, total neural
      tube defects, congenital hydrocephalus, omfalocele, gastroschisis, total
      abdominal wall defects, diaphragmatic hernia, renal agenesis/hypoplasia, cystic
      kidney, Down syndrome and others) in 2006 were analyzed. For a retrospective
      analysis, already published data on birth defects in the Czech Republic were
      used. RESULTS: During 1961-2006 period, totally 6,173,629 children were born on
      the area of the Czech Republic, out of which almost 105,000 with a birth defect.
      Mean incidence was 170 per 10,000 live births. In 1994-2006, totally 1,238,398
      children were born, out of which more than 42,000 with a birth defect. Mean
      incidence was 339 per 10,000 live births (with highest value of 414.58 in 2003).
      In 1994-2006, 6113 cases of prenatally detected birth defects (resulting in
      pregnancy termination) were registered, in relative numbers 49.3 per 10,000 live
      births (2006 63.3 per 10,000). During 1961-2006, totally 2028 anencephaly, 2647
      spina bifida, 462 encephalocele, 5137 total neural tube defects, 3904 congenital
      hydrocefalus, 1627 omfalocele, 941 gastroschisis, 2568 total abdominal wall
      defects, 1754 cystic kidney, 1475 renal agenesis/hypoplasia, 1442 diafragmatic
      hernia, 6328 Down syndrome, 994 oesophageal defects, 1670 anorectal
      malformations, 6856 cleft lip and/or palate and 4440 cleft palate cases were
      registered. Current incidences for 2006 and mean incidences for the 1961-2006
      period (in brackets), both per 10,000 live births were as follows: anencephaly
      2.17 (3.34), spina bifida 4.82 (4.36), encephalocele 1.23 (0.76), total neural
      tube defects 8.22 (8.47), congenital hydrocefalus 3.78 (6.43), omfalocele 3.12
      (2.68), gastroschisis 2.46 (1.55), total abdominal wall defects 5.57 (4.23),
      cystic kidney 8.98 (2.89), renal agenesis/hypoplasia 8.60 (2.43), diafragmatic
      hernia 3.78 (2.38), Down syndrome 20.32 (10.43), oesophageal defects 1.56 (1.61),
      anorectal malformations 2.54 (2.71), cleft lip and/or palate 5.47 (11.11) and
      cleft palate 7.42 (7.19). CONCLUSIONS: The study gives updated results of
      incidences analysis of both pre- and postnatally diagnosed birth defects in the
      Czech Republic until 2006. Some birth defect incidences in live birth are
      decreasing recently (neural tube defects, abdominal wall defects, Down syndrome),
      some are increasing (oesophageal defects, anorectal malformations). Some
      incidences in births are influenced by an increased efficiency of diagnostics
      (renal defects) some remain more or less on the same level (diaphragmatic hernia)
      or just oscillate (facial defects).

PMID- 19170368
TI  - [Ultrasound prenatal diagnostics of birth defects in the Czech Republic in 1994
      2007].
AB  - AIM OF STUDY: An analysis of prenatal diagnostics efficiency of selected birth
      defects in the Czech Republic in 2007. Update of 1994-2007 data according to
      particular defects. TYPE OF STUDY: Retrospective epidemiological analysis of pre-
      and postnatal diagnostics of selected birth defects and prenatal diagnostics
      efficiency. MATERIAL AND METHODS: Data on pre- and postnatally diagnosed birth
      defects in the Czech Republic during 1994-2007 were used. Data on prenatally
      diagnosed birth defects (and for this terminated pregnancies) were collected from
      particular departments of prenatal diagnostics, medical genetics and ultrasound
      diagnostics in the Czech Republic, data on birth defects in births from the
      National Birth Defects Register (Institute for Health Information and
      Statistics). Total numbers and mean incidences of selected types of defects
      (anencephaly, spina bifida, encephalocele, congenital hydrocefalus, omfalocele,
      gastroschisis, diafragmatic hernia, cystic kidney, renal agenesis/hypoplasia,
      transposition of great vessels, tetralogy of Fallot, hypoplastic left heart
      syndrome and coarctation of aorta) during the period under the study were
      analyzed. Prenatal diagnostics efficiency of these defects was also assessed.
      RESULTS: Following total numbers of particular birth defects were registered
      during the 1994-2007 period: anencephaly 380, spina bifida 559, encephalocele
      1134, congenital hydrocefalus 584, omfalocele 351, gastroschisis 389,
      diafragmatic hernia 325, cystic kidney 698, renal agenesis/hypoplasia 679,
      transposition of great vessels 797, tetralogy of Fallot 723, hypoplastic left
      heart syndrome 533 and coarctation of aorta 973. Mean incidences (per 10,000 live
      births) and prenatal diagnostics rate (%, in brackets) were as follows:
      anencephaly 2.81 (95.65), spina bifida 4.13 (61.12), encephalocele 0.99 (77.04),
      congenital hydrocefalus 4.32 (49.61), omfalocele 2.59 (54.97), gastroschisis 2.88
      (77.30), diafragmatic hernia 2.40 (22.02), cystic kidney 5.16 (24.80), renal
      agenesis/hypoplasia 5.02 (25.97), transposition of great vessels 6.93 (7.85),
      tetralogy of Fallot 6.28 (5.87), hypoplastic left heart syndrome 4.63 (39.86) and
      coarctation of aorta 8.46 (3.80). CONCLUSIONS: The study gives updated results of
      ultrasound prenatal diagnostics of selected types of birth defects in the Czech
      Republic during the 1994-2007 period. Ultrasound prenatal diagnostics contributes
      to a decrease of some birth defect in a newborn population as well as to changes
      of their spectrum in births, especially in lethal and most severe ones.
      Ultrasound prenatal diagnostics experienced both qualitative and quantitative
      progress in last years in the Czech Republic, resulting in in higher efficiency
      of prenatal detection of major birth defects in population as well as in
      separating of associated defects and syndromes, particulary those with a general
      good prognosis.

PMID- 19170369
TI  - [Molecular biology of preinvasive and invasive breast tumors].
AB  - OBJECTIVE: To present an overview of molecular characteristics and differences of
      and between preinvasive and invasive breast tumors. DESIGN: Review. SETTING:
      Oncogynecologic center, Clinic of Obstetrics and Gynecology, First Faculty of
      Medicine, Charles University in Prague and General Teaching Hospital, Prague.
      MATERIAL AND METHODS: Review of literature. CONCLUSION: Identification of genetic
      and epigenetic changes in preinvasive and invasive breast tumors can help to
      better classify these lesions and improve and tailor their clinical management.
      Due to completely different biological behavior of morphologically identical
      lesions, it is clear that the matter of classification and clarification of their
      clinical behavior is hidden inside the entire genome or proteome.

PMID- 19170370
TI  - [Oxidative stress in diagnosis and treatment of idiopathic male infertility].
AB  - OBJECTIVE: To summarize available data concerning reactive oxygen species in
      sperm physiology and male infertility. DESIGN: Review article. SETTING: Dept. of
      Obstetrics and Gynecology, Faculty of Medicine and Dentistry, Palacky University
      and University Hospital Olomouc. METHODS: Compilation of published data from
      scientific literature. CONCLUSIONS: The article describes the importance of
      reactive oxygen species and their role in male reproductive health.

PMID- 19170371
TI  - [The clinical significance of sentinel lymph node micrometastases in breast
      cancer].
AB  - OBJECTIVE: The advent of sentinel lymph node biopsy and improvements in
      histopathological and immunohistochemical analysis has increased the rate at
      which micrometastases are identified. However their significance has been the
      subject of much debate. Published studies have reported divergent results
      regarding the significance and implications of axillary lymph node
      micrometastases. Some studies demonstrate no associations, whilst others have
      found these to be indicators of poor prognosis, associated with non-SLN
      involvement, in addition to local and distant failure. The objective of our study
      was to evaluate the impact of sentinel lymph node micrometastatic cancer to
      prognosis of the disease. DESIGN: Retrospective study. SETTING: Departments of
      Gynecology and Obstetrics, Faculty Hospital, Prague. METHODS: From January 2000
      to December 2006 in 87 cases with sentinel axillary node negative cancer we
      reexamined the axillary tissue blocks by serial sectioning, haematoxilin-eosin
      staining and immunohistochemistry. Additional 15 cases of micrometastatic
      sentinel node involvement detected by frozen section were included. The overall
      and disease free survivals of patients with sentinel negative status (N0-67
      cases) and with sentinel node micrometastases (Nmic-35 cases) were evaluated. The
      median follow-up was 60 months (24-96 months). RESULTS: Micrometastases (Nmic)
      were found in 20 cases (23%). From the group of 67 nodes negative patients (N0)
      in 7 cases (10.5%) developed tumor recurrence and from the group of 35 Nmic in 5
      cases developed five tumor recurrences (13.3%). In the group of N0 patients
      developed 2 regional recurrences and 3 patients died, but 2 patients died of
      other causes. In the group of Nmic developed one regional recurrence and 3
      patients died of generalization of disease. CONCLUSION: Our study demonstrated
      that the presence of sentinel node micrometastases is associated with risk of
      development of distant metastases and generalization of the disease, but not with
      higher risk of regional recurrence.

PMID- 19170372
TI  - [Validity of hysteroscopy in clinical setting: single centre analysis of 605
      consecutive hysteroscopies].
AB  - OBJECTIVE: Hysteroscopy represent standard diagnostic and therapeutic method in
      the treatment of endometrial pathology, where patient selection for this
      procedure depends in majority on preoperative uterine ultrasound scan.
      Hysteroscopy can be used for removal of polyps or myomas, endometrial tumor
      resection, synechiolysis, sterilisation or removal of remnants from pregnancy.
      Hysteroscopic surgery can be also an option for patients who wish to preserve the
      uterus for the treatment of recurrent bleeding. We aimed to evaluate the
      validity, complication rate and accuracy of hysteroscopy in correlation with
      preoperative ultrasound and postoperative histopathological findings. SETTING:
      Department of Gynecology and Obstetrics, Jessenius Medical Faculty, Commenius
      University, Martin, Slovak Republic. SUBJECT AND METHOD: Retrospective analysis
      of hysteroscopies for period of 24 months. RESULTS: During study period a total
      of 605 hysteroscopies were performed. In three (0.5%) cases we did not acquired
      sufficient bioptic material required for histopathological diagnosis, thus only
      602 cases were included in the final analyses. The most frequent indication for
      hysteroscopy was history of postmenopausal bleeding (35.88%), followed by
      endometrial polyp (30.9%), hyperplasia (28.24%), cervical polyp (2.32%), corpus
      alienum in the uterus (1.66%) and fertility disorders (1%). Multifactorial
      analysis of hysteroscopy, ultrasound and histopathological findings revealed
      69.41% sensitivity rate for ultrasound finding of endometrial hyperplasia, 48.16%
      sensitivity rate for submucous myoma and 81.72% sensitivity for endometrial
      polyp. The last group of patients showed the highest correlation rate (r)=0.41,
      p<0.01. The false pozitivity of preoperative ultrasound was 30.59%, 51.84% and
      18.28% for mentioned groups, respectively. The association between hysteroscopic
      and histopathological results showed a 97.1% agreement in patients with
      endometrial polyp and 89.3% agreement for cases with endometrial hyperplasia
      (p<0.05). In 66.45% was hysteroscopy associated with biopsy or curretage. The
      causally surgery (tumor or endometrium ablation, myoma or septum resection) was
      performed in 27.9% and in 5.65% others types of intrauterine hysteroscopic sugery
      were done. Out of all surgical procedures polyp ablation represented 63.2%,
      resection of submucous fibroids 21.2%, endometrial resection or ablation 7.2% and
      8.4% others procedures. In studied population we diagnosed 18 (3%) cases of
      endometrial carcinoma (13 cases associated with hyperplasia, 5 with polyp).
      Complication rate was 0.66%. Diagnostic hysteroscopic procedures were associated
      with a significantly lower complication rate (0.19%) than operative procedures
      (0.82%; p<0.05). The most frequent surgical complication was perforation of the
      uterine cavity (three cases 0.50%), followed by fluid overload syndrome (0.17%).
      CONCLUSION: Hysteroscopy is safe diagnostic and operative method with high
      sensitivity, particularly for endometrial polyps. The validity of sonography in
      case of hyperplasia prior surgery could be improved by control uterine ultrasound
      scan reflecting cycle phase one-two days before surgery.

PMID- 19170373
TI  - [Efficacy and safety of solifenacin in daily clinical practice--clinical study
      phase IV].
AB  - OBJECTIVE: Symptoms of urinary urgency, frequency, nocturia with/or without urge
      incontinence, are reffered to as the overactive bladder (OAB). Main option for
      the treatment of the OAB are anticholinergic agents. The aim of the paper is to
      evaluate the efficacy and safety of the solifenacin in the daily clinical
      practice. MATERIAL AND METHODS: 344 patients with OAB symptoms (311 women, 33
      men, average age 57.04 years) were enrolled into the study. Patients were treated
      with solifenacin 5 mg or solifenacin 10 mg in the flexible dosing regimen.
      Efficacy data were obtained from the validated questionnaries and micturion
      diaries. Safety assessment was based on adverse event reporting. RESULTS: We
      observed a highly significant reduction of bladder problems caused by OAB
      (Patient Perception of Bladder Condition--PPBC/PBC score 4.83 at baseline to 3.29
      at endpoint). The decrease of micturion frequency from baseline to endpoint was
      31.19%, decrease of episodes of nocturia was 54.65 % and decrease of incontinence
      episodes was 90.19%. Average number of urgency episodes decresed from 12.46/day
      at baseline to 7.28/day at endpoint (41.6%). Average urgency severity decreased
      from 2.43 at baseline to 1.55 at endpoint (-37.4%). Adverse events were reported
      in 19 patients (5.52%) between visits 1 and 2 and in 16 patients (4.68%) between
      visits 2 and 3. CONCLUSIONS: Results of our phase IV. study showed the excellent
      efficacy and safety profile of solifenacin in the treatment of OAB in accordance
      with results of published phase III. clinical studies.

PMID- 19170374
TI  - [Doctor Andre Corcos: homage to a pioneer of Tunisian medicine].

PMID- 19170375
TI  - Role of immune system, apoptosis and angiogenesis in pathogenesis of rheumatoid
      arthritis and joint destruction, a systematic review.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disorder of
      unknown cause that is notorious for the chronic polyarticular synovial
      inflammation and progressive destruction of affected joints. Understanding the
      pathogenesis of RA provides the basis for optimal management of that disease in
      patients. The pathogenesis of RA was largely explored in many studies in human as
      much as in mice models with collagen II induced arthritis, nevertheless the
      pathogenesis puzzle is still incomplete. AIM: The aim of this systematic review
      was to collect the results of many observations and to put them down into an
      original story of RA set up. METHODS: An exhaustive electronic and library search
      of the relevant literature was carried out through "science direct" and
      "interscience wiley" web sites. The key words used for the search were
      "rheumatoid arthritis", "pathogenesis", "apoptosis", "angiogenesis", "immune
      response" and "joint destruction". RESULTS: The suspected responsible antigen
      isn't yet determined although the great specificity of anti-CCP antibodies
      suggests that this antigen carries probably many citrullinated residues. The
      immuno-pathogenesis of RA involves both the innate and the adaptive immune
      system. In the other hand, apoptosis defect contribute to hyperplasia of
      rheumatoid synovium and in extended half life of fibroblast like synoviocytes
      (FLS), neutrophils and many other cells implied in rheumatoid synovitis.
      Hyperplasia of synovium leads to ischemia and that results in neo-angiogenesis
      with increase of proangiogenic factors such as VEGF. The last part of the
      pathogenesis of RA is the joint destruction resulting from increased MMP
      production and activation of osteoclasts which leads to the breakup of cartilage
      and to bone damage.

PMID- 19170376
TI  - Molecular basis of pituitary development defects.
AB  - Over the last twenty years, the progress made in molecular biology have led to
      the identification of many transcription factor genes, whose mutations has been
      reported as causes of familial hypopituitarism. AIM: Based on a literature
      review, this study is intending to highlight the role of some transcription
      factors in the development of the anterior pituitary gland and to analyse the
      involvement of their dysfunction in some cases of congenital hypopituitarism.
      METHODS: Litterature review. RESULTS: These transcription factors are nuclear
      proteins expressed specifically in certain target cells, in order to control
      genes expression. Their role is fundamental in embryonic and foetal development,
      and particularly in pituitary ontogenesis. Together, they direct the formation of
      anterior pituitary gland, the differentiation, the expansion and the definitive
      function of the five pituitary cell types. In this report, after introducing the
      different stages of anterior pituitary development and differentiation of its
      cell lines, we will briefly highlight the clinical phenotypes associated with
      alterations of different transcription factor genes in both murine models and
      humans.

PMID- 19170377
TI  - [Functioning of a university hospital emergency department].
AB  - BACKGROUND: The emergency department is the part of the hospital where patients
      with undifferentiated emergencies are triaged and receive their initial
      resuscitation and treatment. It provides a 24/7 service with doctors and nurses
      trained in emergency medicine. AIM: We describe our emergency department and its
      activity to emphasize the difficulties and try to suggest a better emergency
      department organization. METHODS: descriptive retrospective study of an emergency
      department and its activity during the year 2004. RESULTS: the department has two
      units: a reception unit with a resuscitation room,a trauma room, an ambulatory
      emergencies room, and an observation unit. There is an average of 89 patients a
      day with peaks in july and august, wednesday and Thursday and between 7.00 and
      2.00 pm and even between 5.00 and 9.00 pm. 86.6% of patients have medical
      pathologies, 60% are graded CCMU II and 11% are admitted in the hospital, half of
      whom in the emergency observation unit with a 28 hours mean stay. CONCLUSION:
      emergency department organization must be fit to local requirements. Improvement
      of emergency functioning requires radiological and biological departments
      reinforcement and medical seniorisation; which may also reduce medical cost.

PMID- 19170378
TI  - [Study of the cutaneous drugs reactions in a teaching hospital in Tunis].
AB  - BACKGROUND: Cutaneous adverse drug reactions correspond to adverse effects with
      cutaneous expression resulting from the systemic penetration of a drug in the
      body. The aim of this study is to evaluate the various clinical pictures of RCM,
      their epidemiologic characteristics as well as the different causative drugs,
      through a retrospective hospital series. METHODS: It is about a retrospective
      study about all the patients consulting and/or hospitalized for suspicion of an
      adverse cutaneous drug reaction led to the service of dermatology of the teaching
      hospital Habib Thameur of Tunis over a 3-year period (from January 2002 to
      December 2004). The diagnosis was based on a beam of clinical and anamnestic
      arguments. Only the patients having a positive pharmacovigilance investigation
      were retained. RESULTS: 28 patients were retained for this study. The macular and
      papular exanthema represented the most frequent clinical aspects followed by
      acute urticaria and fixed drug eruption. The antibiotics represented the most
      causative drugs followed by analgesics and non steroidal anti-inflammatory.
      CONCLUSION: We record a lower frequency of cutaneous adverse drug reactions in
      comparison with the literature. We also find a high frequency of severe forms and
      stress on the difficulties encountered in the identification of the causativele
      drugs. Though, a close cooperation between the various hospital structures and
      pharmacovigilance centers is mandatory.

PMID- 19170379
TI  - [Epidemiological and clinical profile of vitiligo in Tunisia: retrospective study
      of 503 cases].
AB  - BACKGROUND: Vitiligo is an acquired leucoderma whose etiology remains unknown.
      Its frequency in the world is estimated at 1%. AIM: The purpose of our study is
      to asses, with through a retrospective hospital series, the epidemilogic,
      clinical, therapeutic and course of this dermatosis and to compare our results
      with those of the literature. METHODS: This is a retrospective study of
      consecutive patients attending the outpatient dermatological department at
      Charles Nicolle Hospital in Tunis over a 5 year-period (from June 1999 to July
      2000). RESULTS: 503 patients were reviewed during a 5-year period. They were 288
      women and 215 men (sex-ratio F/H = 1.33). The average age was 28.2 years
      (extremes of 3 and 80 years). The peak of frequency was located in the 2nd decade
      of the life (26%). A family history of vitiligo was found in 27% of the cases.
      The average time of consultation was 21 months. The localization of the lesions
      was ubiquitary prevalent at the uncovered areas. An association with other
      pathological conditions was found in 23% of cases. Most patients were treated by
      a photochemotherapy (78.2%). Photoprotection was advised among all patients. The
      course was specified in 112 cases corresponding to a partial (28.9%) or a
      complete repigmentation (0, 8%), a stabilization of lesions (41.6%) and an
      extension (26%). CONCLUSION: Our results are consistent with the literature
      stressing the frequency of vitiligo which can cause an aesthetic and
      psychological damage of variable and sometimes major importance.

PMID- 19170380
TI  - [Erythema nodosum: profile in a Tunisian teaching hospital].
AB  - BACKGROUND: Erythema nodosum (EN) is the most frequent acute nodular
      hypodermatitis. Etiologies of EN are varied although a similar clinical
      presentation. The aim of our study is to establish epidemio-clinical
      characteristics of EN in 103 patients. METHODS: (62 in care (january 1980
      december 2005) and 41 consultants (january 1991-december 2005) were seen on the
      dermatology unit of the Rabta hospital. We have only included patients that had
      done: blood count, chest X-Ray, ASLO, tuberculin intradermoreaction,
      transaminase, inflammation marker. RESULTS: We had 86 women and 17 men with a
      mean age of 36,5 years. Lesions were located in lower limbs in 88 cases. The main
      etiologies were: post streptococcal infections (42 cases), tuberculosis (8
      cases), Crohn disease (8 cases), Behcet disease (7 cases) and sarcoidosis (5
      cases). EN was idiopathic in 23 patients. The most common provoking agent of EN
      varies from a country to another and even in the same country from a study to
      another. In Tunisia, post streptococcal infections and Behcet disease still
      frequent etiologies for EN, sarcoidosis and inflammatory colites are more and
      more found unlike tuberculosis which is less incriminated than before. In case of
      EN it is reasonable to begin etiological enquiry by common causes.

PMID- 19170381
TI  - Congenital cataract etiology.
AB  - AIM: Our purpose is to study the aetiologies of congenital cataracts, and to
      establish an approach to decision making of etiological diagnosis. METHODS: We
      included 85 children in a cross sectional study. The mean age was 4.5 years.
      These patients underwent a complete ophthalmologic and paediatric examination,
      and etiological investigation. RESULTS: An aetiology of congenital cataracts was
      found in 62.5% of cases. Hereditary was the most common cause, it constituted
      42.3% of etiologies. Among these cases 77.7% were autosomal recessive. 16.4% of
      congenital cataracts were associated with general diseases or dysmorphology
      syndromes. Metabolic diseases and intrauterine infections were found in 7 % and
      4.7% of cases respectively. CONCLUSION: Heredity remains the most common etiology
      of congenital cataracts.

PMID- 19170382
TI  - [Nocturnal gastroesophageal reflux disease in asthmatics patients: a pHmetric
      study about 81 cases].
AB  - AIMS: To determine the frequency of gastroesophageal reflux disease on 24-hour
      esophageal pH monitoring in asthmatics patients and to evaluate the clinical and
      pHmetric characteristics of nocturnal reflux in these patients. METHODS: We
      conducted a retrospective study based on results of 24-hour esophageal pH
      monitoring during a 10-year period in asthmatics patients with or without
      digestive symptoms of gastroesophageal reflux disease. RESULTS: We studied 81
      patients (37 men, 44 women; mean age: 32 years). Gastroesophageal reflux was
      found in 42 patients (52%). Nocturnal reflux was observed in 35 patients (43%),
      mostly in association with pathological reflux in the total period (32 cases).
      Presence of digestive symptoms was the only associated factor to gastroesophageal
      reflux during 24-hour, in nocturnal or in diurnal period. Compared to the diurnal
      period, the nocturnal period was characterized by fewer number of reflux episodes
      (22.69 + 23 vs 70.16 + 56.15; p<0.001), more longer duration of reflux episodes
      (25.92 + 23.34 minutes vs 15.52 + 16.27 minutes; p=0.02), fewer respiratory
      symptoms (2.24 + 1.89 vs 6.18 + 4.12; p=0.01) and better symptomatic correlation
      (13/17:76% vs 9/24:37%; p=0.02). CONCLUSION: Gastroesophageal reflux disease is
      frequent in asthma. Nocturnal reflux is associated with overall reflux on the 24
      hour examination. Nocturnal period is characterized by more longer reflux
      episodes and better symptomatic correlation.

PMID- 19170383
TI  - [Evolution of antibiotic consumption in an intensive care burn department].
AB  - BACKGROUND: The increasing consumption of antibiotics in hospitals and the
      economic implications of this increase lead to survey this consumption in the
      various hospital units. AIM: Our study proposes to measure the annual antibiotic
      use and antimicrobial resistance in an intensive care Burn department in order to
      manage the control measures. METHODS: The study was conducted during a 5 year
      period (1 January 2000 to 31 December 2004). The average number of admissions was
      204/year and the mean number of hospitalisation was 4036/year. Antimicrobial
      susceptibility testing was performed by disk diffusion method. Susceptibility
      testing data were stored in a laboratory data base using whonet 5.3 software. The
      consumption of following antibiotics: imipenem, ceftazidime, ofloxacin,
      ciprofloxacin, piperacillin-tazobactam was measured by antimicrobial density (AD)
      witch takes into account the quantity of antibiotics in Grams converted to daily
      defined dose (DDD) and number of hospitalization days. The daily defined dose
      (DDD) was proposed by WHO. The calculation of the AD for each molecule was
      carried out according to the following formula: [AD = Quantity consumed in grams
      for the particular antimicrobial X 1000]/[DDD for that antimicrobial X number of
      days hospitalizations]. RESULTS: There was statistically significant relationship
      between increasing use of ceftazidime and ceftazidime resistant Klebsiella
      pneumoniae (rs=0.93; p=0.02). The use of ceftazidime was not significantly
      associated with resistance to this molecule in P. aeruginosa (rs=0.76 ; p=0.13).
      Concerning the fluoroquinolones, there was statistically significant relation
      ship between increasing use of ciprofloxacin and rate ciprofloxacin resistant P.
      aeruginosa (rs=0.89,P=0.043). Furthermore, the consumption of ciprofloxacin was
      significantly correlated to imipenem resistance in P. aeruginosa (rs=0.87, p=0.05
      ). However, the consumption of imipenem was not significantly correlated to
      resistance of this drug in P. aeruginosa (rs=0.45; P=0,4). CONCLUSION: The
      monitoring of both antibiotic consumption andantibiotic resistance is necessary
      to set up targeted policies and to control their effectiveness. Nevertheless this
      monitoring must be integrated into global policy of good use and control of
      antibiotics.

PMID- 19170384
TI  - [Prognostic factors for survival in cirrhosis].
AB  - BACKGROUND: Assessment of prognosis in patients with cirrhosis is important so as
      to plan their management as well as the choice of major procedures. The aim of
      the present study was to determine the survival rates and to identify indicators
      associated with shorter life expectancy in Tunisians patients with cirrhosis.
      METHODS: This is a retrospective study of patients with cirrhosis admitted during
      14-years period. We studied clinical and biochemical characteristics of all
      patients and the occurrence of decompensation or complication (gastro-intestinal
      bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, hepato-renal
      syndrome, hepatocellular carcinoma). The overall survival, mortality rate and
      causes of death were reviewed. Univariate and multivariate analysis was performed
      on all variables to identify parameters associated with a lower life expectancy.
      RESULTS: We studied 85 patients (50 females/35 males) with a mean age of 57
      years. Mean follow up was 31 months. The overall survival was 47% at 5 years.
      With univariate analysis, 13 variables were associated with a poor prognosis:
      male sex, jaundice, ascites, and decompensation at admission, increased serum
      gammaglobulin, gammaGT, bilirubine and ASAT levels, Child-Pugh C, occurrence of
      spontaneous bacterial peritonitis, hepatic encephalopathy, hepato-renal syndrome
      and hepatocellular carcinoma. With multivariate analysis, 2 variables were
      independently correlated with survival:male sex and elevated gammaGT. CONCLUSION:
      In our study, male sex, increased serum gammaGT and gammaglobulin are uncommon
      parameters that may predict survival in cirrhotic patient. The Child-Pugh score
      was a good index for assessing the prognosis.

PMID- 19170385
TI  - [Comparative study of appendical mucocela and pseudomyxoma peritonei. About 25
      cases].
AB  - AIM: to study the clinicopathological features of the different types of
      appendical mucocele and to compare them with those of pseudomyxoma peritonei.
      METHODS: 25 cases of appendical mucocele were operated in the Cap-Bon region in
      Tunisia during a period of 13 years from 1994 to 2006. RESULTS: 9 retentionnal
      cysts, 13 mucinous cystadenomas, one serrated adenoma, one hyperplasia of the
      mucosa and one cystadenocarcinoma were diagnosed. Five cystadenomas as well as
      the only case of cystadenocarcinoma were associated with pseudomyxoma peritonei.
      Pseudomyxoma peritonei occurred 20 years later than in simple appendiceal
      mucocele and complicated 5 cases of cystadenoma with low grade dysplasia and 1
      case of cystadenocarcinoma. CONCLUSION: Preoperative diagnosis of appendical
      mucocele and pseudomyxoma peritonei should be made on scannographic features in
      order to assess the adequate surgical management.

PMID- 19170386
TI  - [Toward optimization of small cell lung cancer management].
AB  - Small cell carcinoma represents 20 to 25 % of all lung cancers. It is
      characterized by his quickly dissemination. Chemotherapy is the comer stone of
      small cell lung cancer therapy. However, therapeutic approach are depending on
      patient's performans states and the disease's extension. The role of radiotherapy
      is established in the treatment of limited disease. However irradiation's
      modalities are still discussed. Surgery, usually, contraindicated is, actually,
      possible in early stages (T1T2N0). Recent advances in molecular biology have
      created new molecular targeted therapies for SCC but the benefits are not still
      evaluated. In this article, we review briefly classic strategies that have been
      evaluated in the management of patients with small cell carcinoma. This review
      will, also, focus in the main novel cytotoxic drugs and radiotherapy's modalities
      and for their clinical implication.

PMID- 19170387
TI  - Recurrent obstructions after resonance stent placement in the treatment of
      ureteral compression from malignant disease.
AB  - BACKGROUND: The Resonance ureteral stent is a newly developed all-metallic double
      pigtail ureteral stent allowing a palliative diversion on a patient with
      malignant ureteral obstruction. AIM: To define selection criteria of good
      candidates for Resonance stent. CASE: A 62-year-old woman was admitted to the
      emergency department with complaining of severe right flank pain and anuria.
      Twelve days earlier, we had placed retrogradely a ureteral metallic Resonance
      stent (Resonance; Cook Ireland Ltd,Limerick, Ireland) for the treatment of a
      ureteral compression from pelvic recurrence of an appendical colloid mucosal
      carcinoma in a solitary functioning right kidney. A percutaneous nephrostomy
      catheter was placed, and an antegrade nephrostogram demonstrated complete distal
      ureter obstruction. The patency of the ureteral stent was restored spontaneously
      and then, nephrostomy catheter was removed. Two weeks later, she presented with
      obstructed ureteral stent. Percutaneous nephrostomy was performed and Resonance
      stent was removed definitively. Ureteroscopy with biopsy confirmed the tumour
      extension into the ureteral lumen. CONCLUSION: The risk of subsequent obstruction
      after Resonance metallic ureteral stent placement is real. Patients with intra
      ureteral tumour extension are presumably not good candidates for Resonance stent
      management.

PMID- 19170388
TI  - Spontaneous ovarian hyper stimulation syndrome and deep vein thrombosis in a non
      pregnant woman: case report.
AB  - AIM: To assess aetiological factors and complications in a patient with severe
      ovarian hyperstimulation syndrome (OHSS) and internal jugular vein thrombosis.
      CASE: A 27-year-old non pregnant woman with bilateral ovarian masses who had
      underwent laparotomy for suspicion of malignant tumor. The pathological
      examination disclosed malignancy and the diagnosis of OHSS were confirmed. The
      postoperative evolution was complicated by internal jugular, subclavian vein
      thrombosis and pulmonary embolism. All biological parameters were negative. The
      evolution was good. CONCLUSION: The incidence of thromboembolism in women with
      OHSS is low and the typical finding is deep venous thrombosis in the neck area.
      Preventive measure of OHSS is very important, and the patients must be treated
      timely and correctly once OHSS occurs.

PMID- 19170389
TI  - Intraligamentous ganglion cyst of the anterior cruciate ligament (about a case).
AB  - UNKNO WLOGEMENT: Ganglion cysts have been reported in all joints, with varying
      frequency in location. A few cases have been described concerning ganglia of the
      anterior cruciate ligament (ACL) particularly intraligamentous cysts. AIM: The
      aim of the study is to report specific particularities of intraligamentous
      ganglion cyst of the ACL. CASE: We report a new case of intraligamentous ganglion
      cyst of the anterior cruciate ligament treated successfully with arthroscopic
      aspiration followed by partial excision of the cyst wall after MRI examination.
      The MR findings, clinical features and arthroscopic findings were evaluated
      comparatively. Diagnosis was confirmed by means of histological study after
      arthroscopic excision. The cyst was fluid-filled, with low T1-weighted signal
      intensity and high T2-weighted signal intensity. Pain was the most frequent
      clinical sign without any history of trauma. Postarthroscopy outcome was
      painless. Histologic diagnosis corresponded to ganglion cyst. CONCLUSION: An
      intraligamentous ganglion cyst of the ACL is extremely rare and suggests some
      diagnostic and therapeutic particularities.

PMID- 19170390
TI  - [The laryngopyocele].
AB  - BACKGROUND: The laryngopyocele is a laryngocele complication. AIM: We report two
      cases that were treated in Habib Thameur Hospital ENT service. CASES: There were
      an 81 old woman and a 31 old man who consult for an infectious syndrome with a
      lateral neck masses. The diagnosis was obtained by clinical and endoscopic
      examination and was confirmed by CT. The man was operated. On antibiotics were
      precribed for both. They had a well recovery.

PMID- 19170391
TI  - [Management of pheochromocytoma during pregnancy: about three cases].
AB  - BACKGROUND: Pheochromocytoma is a rare disease that can be diagnosed for the
      first time during pregnancy. Diagnosis is difficult because it can mimic common
      gravid hypertension. Maternal and fetal prognosis depends on early diagnosis and
      adequate multidisciplinary management. AIM: We report 3 cases of pregnant
      patients with pheochromocytoma. CASES: For the first patient, diagnosis was made
      before pregnancy and pheochromocytoma was treated surgically at 20 weeks of
      pregnancy with good evolution. The second patient was hospitalized in a severe
      preeclampsia, acute pulmonary edema and fetal demise with fatal outcome.
      Pheochromocytoma was diagnosed during autopsy. The third patient had medical
      abortion of pregnancy because of tumor recurrence after surgical treatment. Rare
      association to pregnancy and clinical signs of pheochromoytoma as hypertension
      renders diagnosis difficult. A systematic etiology research to early hypertension
      during pregnancy can allow better screening of pheochromocytoma and improvement
      of foeto-maternal prognosis.

PMID- 19170392
TI  - [Sigmoido-vesical fistula: a case report].
AB  - BACKGROUND: Colovesical fistula is a rare complication of inflammatory and
      neoplasic pelvic diseases (0.2%). AIM: To report a new case. CASE: We report the
      case of a 74-year-old woman, with a charged previous medical history and had not
      had hysterectomy. She was admitted because of cystitis with haematuria associated
      to faecaluria and pneumaturia confirmed by an intravenous pyelogram. Water
      soluble contrast medium show the sigmoidovesical fistula. A sigoid sticture is
      identified at colonoscopy and biopsy was realised. The patient had had
      sigmoidectomy with Hartmann's procedure. Histologic study confirm the
      diverticulatis with peridiverticular abcess and fistula. We suggest that early
      diagnosis and management of sigmoid diverticulatis is required to prevent
      complicatins like stricture and fistula.

PMID- 19170393
TI  - Dialogues in clinical neuroscience. Remission in depression.

PMID- 19170394
TI  - Towards achieving remission in the treatment of depression.
AB  - The burden of depressive illness constitutes a major public health issue. Despite
      real progress and better tolerance of new antidepressant medications, a
      significant number of depressed patients still suffer from rather severe residual
      depressive symptoms.This relative lack of efficacy clearly interferes with their
      psychosocial functioning and their quality of life. In addition, it is now well
      recognized that the failure to reach full clinical remission after antidepressant
      treatment involves a high risk of relapse or recurrence in patients suffering
      from major depression, This paper reviews the concept of remission across
      different definitions, and the potential risk factors associated with the failure
      to reach clinical remission. The identification of specific residual symptoms in
      nonremitted patients is also of great importance, in order to assess the
      predictive value of those symptoms in relation to relapse and recurrence. Some
      methodological issues are also discussed, as well as various therapeutic
      strategies aimed at relieving residual depressive symptoms. Clinical remission
      remains a gold standard and a primary objective of modern antidepressant therapy.

PMID- 19170395
TI  - Treatment strategies to improve and sustain remission in major depressive
      disorder.
AB  - Major depressive disorder (MDD) is an often chronic, recurrent illness affecting
      large numbers of the general population. In recent years, the goal of treatment
      for MDD has moved from mere symptomatic response to that of full remission (i.e.,
      minimal/no residual symptoms). The recent Sequenced Treatment Alternatives to
      Relieve Depression (STAR*D) trial showed that even with systematic measurement
      based treatment, approximately one third of patients reach full remission after
      one treatment trial, with only two thirds reaching remission after four treatment
      trials. Treatment-resistant depression (TRD) is therefore a common problem in the
      treatment of MDD, with 60% to 70% of all patients meeting the criteria for TRD.
      Given the huge burden of major depressive illness, the low rate of full recovery
      remains suboptimal. The following article reports on some current treatment
      strategies available to improve rates of, and to sustain, remission in MDD.

PMID- 19170397
TI  - Pharmacogenomic strategy for individualizing antidepressant therapy.
AB  - Despite remarkable progress, pharmacotherapy in general, including that for the
      treatment of depressive conditions, has often ignored the magnitude and clinical
      significance of the huge interindividual variations in pharmacokinetics and
      pharmacodynamics, resulting in poor compliance, suboptimal therapeutic effects,
      and treatment resistance. Advances in pharmacogenomics and computer modeling
      technologies hold promise for achieving the goals of "individualized"
      ("personalized") medicine. However, the challenges for realizing such goals
      remain substantial. These include the packaging and interpretation of genotyping
      results, changes in medical practice (innovation diffusion), and infrastructural,
      financing, ethical, and organizational issues related to the use of new
      information.

PMID- 19170396
TI  - Cellular and molecular mechanisms in the long-term action of antidepressants.
AB  - The hypotheses on the pathophysiology of depression/mood disorders and on
      antidepressant mechanisms have greatly changed in recent years. The classical
      monoamine hypothesis was revealed to be simplistic, in that it could not explain
      the temporal delay in the therapeutic action of antidepressants. Converging lines
      of evidence have shown that adaptive changes in the several mechanisms of
      neuroplasticity are likely to be the cellular and molecular correlates of
      therapeutic effect. In this article, several mechanisms of neuroplasticity are
      analyzed in relation to the mechanism of antidepressants, ranging from changes in
      gene expression (including neurotrophic mechanisms), to synaptic transmission and
      plasticity, and neurogenesis. We propose that the current version of the
      hypothesis of antidepressant mechanism simply be called the "hypothesis of
      neuroplasticity". In the final section, we also briefly review the main current
      novel strategies in the pharmacology of depression and the new putative targets
      for antidepressants, with particular emphasis on nonmonoaminergic mechanisms.

PMID- 19170398
TI  - Toward achieving optimal response: understanding and managing antidepressant side
      effects.
AB  - The safety and tolerability of antidepressants have improved considerably over
      the past two decades. Nevertheless, antidepressant side effects are still common
      and problematic. The majority of patients treated with contemporaty agents
      experience one or more bothersome side effects. These side effects often create
      barriers to achieving depressive remission, as well as to preventing relapse and
      recurrence. Clinicians tend to underestimate the prevalence of side effects, and
      as many as one quarter of patients discontinue their antidepressants because of
      difficult-to-tolerate side effects; others may continue on antidepressant therapy
      but experience diminished quality of life related to troublesome side effects.
      This article reviews the prevalence of side effects, the impact of side effects
      on treatment adherence, and methodological issues including the challenge of
      distinguishing side effects from residual depressive symptoms, discontinuation
      effects, and general medical problems. In addition, we address the most common
      side effects such as sexual dysfunction, gastrointestinal problems, sleep
      disturbance, apathy and fatigue, and offer strategies for management that may
      help patients achieve optimal response to pharmacotherapy

PMID- 19170400
TI  - Partial remission, residual symptoms, and relapse in depression.
AB  - Partial remission from depression, with residual symptoms, is an important
      problem in depression. This paper reviews the frequency and features of this
      outcome, and its association with relapse. Residual symptoms occur in many
      depressed patients after acute treatment. They span the typical symptoms of
      depression, except those characteristic of severe disorders. Other persistent
      abnormalities include social dysfunction, dysfunctional attitudes, hypothalamic
      pituitary-adrenal axis overactivity, shortened REM sleep latency, and mood
      lowering after tryptophan depletion. Associations of some of these with residual
      symptoms are not clear. There is growing evidence for similar residual symptoms
      in bipolar disorder, particularly bipolar depression. The most important
      consequence of residual symptoms is a much-increased risk of relapse,
      particularly in the first year. Residual symptoms are a strong indication for
      vigorous and longer than usual continuation of antidepressant treatment in order
      to prevent relapse. There is good evidence for the use of cognitive therapy as an
      adjunct.

PMID- 19170399
TI  - Incomplete response in late-life depression: getting to remission.
AB  - Incomplete response in the treatment of late-life depression is a large public
      health challenge: at least 50% of older people fail to respond adequately to
      first-line antidepressant pharmacotherapy, even under optimal treatment
      conditions. Treatment-resistant late-life depression (TRLLD) increases risk for
      early relapse, undermines adherence to treatment for coexisting medical
      disorders, amplifies disability and cognitive impairment, imposes greater burden
      on family caregivers, and increases the risk for early mortality, including
      suicide. Getting to and sustaining remission is the primary goal of treatment,
      yet there is a paucity of empirical data on how best to manage TRLLD. A pilot
      study by our group on aripiprazole augmentation in 24 incomplete responders to
      sequential SSRI and SRNI pharmacotherapy found that 50% remitted over 12 weeks
      with the addition of aripiprazole, and that remission was sustained in all
      participants during 6 months of continuation treatment. In addition to controlled
      assessment, evidence is needed to support personalized treatment by testing the
      moderating role of clinical (e.g., comorbid anxiety, medical burden, and
      executive impairment) and genetic (eg, selected polymorphisms in serotonin,
      norepinephrine, and dopamine genes) variables, while also controlling for
      variability in drug exposure. Such studies may advance us toward the goal of
      personalized treatment in late-life depression.

PMID- 19170401
TI  - Predictors, moderators, and mediators (correlates) of treatment outcome in major
      depressive disorder.
AB  - Major Depressive Disorder (MDD) is a prevalent illness that is frequently
      associated with significant disability, morbidity and mortality Despite the
      development and availability of numerous treatment options for MDD, studies have
      shown that antidepressant monotherapy yields only modest rates of response and
      remission. Clearly, there is an urgent need to develop more effective treatment
      strategies for patients with MDD. One possible approach towards the development
      of novel pharmacotherapeutic strategies for MDD involves identifying
      subpopulations of depressed patients who are more likely to experience the
      benefits of a given (existing) treatment versus placebo, or versus a second
      treatment. Attempts have been made to identify such "subpopulations",
      specifically by testing whether a given biological or clinical marker also serves
      as a moderator, mediator (correlate), or predictor of clinical improvement
      following the treatment of MDD with standard, first-line antidepressants. In the
      following article, we will attempt to summarize the literature focusing on
      several major areas ("leads") where preliminary evidence exists regarding
      clinical and biologic moderators, mediators, and predictors of symptom
      improvement in MDD. Such clinical leads will include the presence of
      hopelessness, anxious symptoms, or medical comorbidity. Biologic leads will
      include gene polymorphisms, brain metabolism, quantitative
      electroencephalography, loudness dependence of auditory evoked potentials, and
      functional brain asymmetry.

PMID- 19170402
TI  - Incomplete remission in depression: role of psychiatric and somatic comorbidity.
AB  - Depression is one of the most pressing public health issues, because of its high
      lifetime prevalence and because it is associated with substantial disability. In
      depressed patients, psychiatric and medical comorbidity is the rule rather than
      the exception. About 60% to 70% of depressed patients have at least one, while
      30% to 40% have two or more, concurrent psychiatric disorders, Among these,
      anxiety disorders and substance use disorders are the most common axis I
      comorbidities. Furthermore, two thirds of depressed patients have at least one
      comorbid medical illness. Among depressed patients, those with a current comorbid
      psychiatric condition (in particular an anxiety or substance use disorder) or
      medical illness seem to have an impaired response and remission rate during
      treatment compared with those patients without comorbidity. However, in depressed
      patients who all have the same comorbid condition, the relative benefit of an
      antidepressant compared with placebo appears to be equal to those effects
      achieved in depressed patients without comorbidity. These findings raise
      important research and treatment issues regarding the generalizability from
      randomized controlled trials that to exclude patients tend to exclude patients
      with comorbidity.

PMID- 19170404
TI  - Sleep disturbances and depression: risk relationships for subsequent depression
      and therapeutic implications.
AB  - The majority of individuals with depression experience sleep disturbances.
      Depression is also over-represented among populations with a variety of sleep
      disorders. Although sleep disturbances are typical features of depression, such
      symptoms sometimes appear prior to an episode of depression. The bidirectional
      associations between sleep disturbance (especially insomnia) and depression
      increase the difficulty of differentiating cause-and-effect relationships between
      them. Longitudinal studies have consistently identified insomnia as a risk factor
      for the development of a new-onset or recurrent depression, and this association
      has been identified in young, middle-aged, and older adults. Studies have also
      observed that the combination of insomnia and depression influences the
      trajectory of depression, increasing episode severity and duration as well as
      relapse rates. Fortunately, recent studies have demonstrated that both
      pharmacological and nonpharmacological interventions for insomnia may favorably
      reduce and possibly prevent depression. Together, these findings suggest that
      sleep-related symptoms that are present before, during, andlor after a depressive
      episode are potentially modifiable factors that may play an important role in
      achieving and maintaining depression remission.

PMID- 19170403
TI  - Psychosocial determinants of recovery in depression.
AB  - There is a growing body of literature on residual symptoms after apparently
      successful treatment. The strong prognostic value of subthreshold symptomatology
      upon remission and the relationship between residual and prodromal symptomatology
      (the rollback phenomenon) have been outlined. Most residual symptoms also occur
      in the prodromal phase of depression and may progress to become prodromes of
      relapse. These findings entail important implications. It is necessary to closely
      monitor the patient throughout the different phases of illness and to assess the
      quality and extent of residual symptoms. A more stringent definition of recovery,
      which is not limited to symptomatic assessment, but includes psychological well
      being, seems to be necessary. New therapeutic strategies for improving the level
      of remission, such as treatment of residual symptoms that progress to become
      prodromes of relapse and/or increasing psychological well-being, appear to yield
      more lasting benefits. The sequential model may provide room for innovative
      treatment approaches, including the use of drugs for specifically addressing
      residual symptoms. As occurs in other medical disorders (such as diabetes and
      hypertension), the active role of the patient in achieving recovery (self-therapy
      homework) should be pursued.

PMID- 19170405
TI  - Recognition and management of common ectoparasitic diseases in travelers.
AB  - This review article summarizes the ectoparasitic diseases likely to be seen by a
      Western dermatologist. The article aims to cover both endemic diseases and those
      likely to present in the returning traveler. Tungiasis is due to the gravid sand
      flea (Tunga penetrans) embedding into the stratum corneum of a human host. As the
      flea is a ground dweller, lesions are usually present on the feet and are
      classically periungual. The sand flea is eventually shed spontaneously but to
      reduce the infection risk, early surgical removal is recommended. Infestation by
      the Diptera species of fly causes myiasis, which may be primary, secondary, or
      accidental. The botfly (Dermatobia hominis) is one of the causes of primary
      myiasis covered in this article. Traditionally, botfly larvae are forced to
      partially emerge by occluding the breathing apparatus, following which manual
      extraction can occur. Alternatively, the larvae can be surgically removed. The
      common bed bug (Cimex lectularius) has experienced a resurgence over the past 10
      years. Bites are typically arranged in clusters or a linear fashion and vary from
      urticated wheals to hemorrhagic blisters. Treatment is symptomatic with
      antihistamines and topical corticosteroids. In addition, bed bugs need to be
      eradicated from furniture and soft furnishings. Ticks are part of the Arachnid
      class of joint-legged animals and can transmit a variety of infections. This
      article briefly discusses Mediterranean spotted fever, Rocky Mountain spotted
      fever, and Lyme disease as well as describing tick avoidance measures. Scabies
      (Sarcoptes scabiei var hominis) is highly contagious and widely distributed
      around the world. It is common in the returning traveler and can require a high
      index of suspicion to diagnose. The treatment of choice in the US, UK, and
      Australia is permethrin 5% dermal cream, applied on two occasions, 1 week apart.

PMID- 19170406
TI  - Urticaria : a review.
AB  - Urticaria is often classified as acute, chronic, or physical based on duration of
      symptoms and the presence or absence of inducing stimuli. Urticarial vasculitis,
      contact urticaria, and special syndromes are also included under the broad
      heading of urticaria. Recent advances in our understanding of the pathogenesis of
      chronic urticaria include the finding of autoantibodies to mast cell receptors in
      nearly half of patients with chronic idiopathic urticaria. These patients may
      have more severe disease and require more aggressive therapies. Extensive
      laboratory evaluation for patients with chronic urticaria is typically
      unrevealing and there are no compelling data that associate urticaria with
      chronic infections or malignancy. Pharmacologic therapy consists primarily of the
      appropriate use of first- and second-generation histamine H(1) receptor
      antihistamines. Additional therapy may include leukotriene receptor antagonists,
      corticosteroids, and immunomodulatory agents for severe, unremitting disease.
      Despite our greater understanding of the pathogenesis of urticaria, the condition
      remains a frustrating entity for many patients, particularly those with chronic
      urticaria.

PMID- 19170407
TI  - Role of high-variable frequency ultrasound in preoperative diagnosis of glomus
      tumors: a pilot study.
AB  - BACKGROUND: Accurate preoperative imaging of glomus tumors improves the outcome
      of surgery. Currently, MRI is frequently recommended for preoperative assessment
      although this requires the use of intravenous contrast media and may be less
      efficient at detecting tumors <3 mm in diameter. Recent developments in high
      variable frequency ultrasound (HVFUS) mean re-evaluation of the possible role of
      ultrasound in the preoperative detection of glomus tumors appears appropriate.
      OBJECTIVE: To assess the capabilities of contemporary HVFUS in relation to
      preoperative detection and characterization of glomus tumors. METHODS: Seven
      patients (all women, aged 38-66 years, mean age 51.3 years) suspected on clinical
      grounds of having a glomus tumor were evaluated with high-resolution color
      Doppler ultrasound using a compact linear probe that varies from 7 to 15 MHz in
      frequency. The results were compared with histology. RESULTS: The tumors and
      their exact location were identified in all cases. The tumors appeared as
      hypoechoic nodules with high vascularity in the nail bed, together with
      remodeling of the underlying bone. Small tumors (0.9 mm depth) were also
      identified. Arterial flow was identified inside all tumors. Peak systolic
      velocity varied greatly, but the mean was 11.3 +/- 9.1 cm/sec (range: 3.7-26.1
      cm/sec). CONCLUSION: Recent developments in HVFUS have made it possible to
      identify small glomus tumors in real time and with high resolution. The procedure
      does not require administration of intravenous contrast media and provides good
      information about lesional blood flow and the surrounding structures. These
      results suggest that HVFUS may play a larger role in the preoperative assessment
      of glomus tumors in the future.

PMID- 19170408
TI  - Granulomatous slack skin presenting as acquired ichthyosis and muscle masses.
AB  - We describe a case of granulomatous slack skin in a 31-year-old woman with an
      unusual presentation of acquired ichthyosis and muscular masses involving four
      limbs over 3 years. Vesicles and ulcerative skin nodules first appeared only 3
      months prior to diagnosis. The diagnosis was confirmed after sequential biopsies
      of muscle, skin lesions, and lymph nodes, together with molecular genetic
      studies. The patient responded poorly to various therapies, including
      thalidomide, and died of doxorubicin-related cardiomyopathy.

PMID- 19170409
TI  - Pregnancy as a possible etiologic factor in erythema annulare centrifugum.
AB  - Immunologic, endocrine, metabolic, and vascular changes that occur during
      pregnancy may adversely affect the skin. This article describes a patient who
      developed erythema annulare centrifugum during pregnancy. The eruptions
      disappeared shortly before delivery. To the author's knowledge, this is only the
      third report of erythema annulare centrifugum associated with pregnancy. This
      article discusses the possible connections between erythema annulare centrifugum
      and pregnancy that may be demonstrated in this case.

PMID- 19170410
TI  - Bullous pemphigoid induced by penicillamine in a patient with Wilson disease.
AB  - We report a 47-year-old man with Wilson disease who developed bullous lesions on
      the trunk and extremities after 20 years of penicillamine treatment. The
      histologic and immunofluorescence findings were diagnostic of bullous pemphigoid.
      When penicillamine was replaced by zinc sulfate, the patient's bullous skin
      lesions improved rapidly. However, after 2 months of zinc sulfate treatment, the
      patient's skin condition remained improved but his neurologic disease became
      worse and penicillamine was reinstituted. Bullous lesions recurred within 1 week
      and the diagnosis of penicillamine-induced bullous pemphigoid was confirmed. This
      is the first report of penicillamine-induced bullous pemphigoid in a patient with
      Wilson disease.

PMID- 19170411
TI  - Healing of ulcers due to cryofibrinogenemia with colchicine and high-dose
      pentoxifylline.
AB  - Cryofibrinogenemia is due to the presence of reversibly cold-precipitating plasma
      proteins and material, consisting mostly of fibrinogen, fibronectin, and fibrin.
      This condition can be idiopathic or secondary to infection, thromboembolic
      states, neoplasm, or connective tissue disease. The characteristic lesions of
      cryofibrinogenemia include purpura and ulcerations. Histologically, the lesions
      of cryofibrinogenemia demonstrate fibrin thrombi within vessels, with no evidence
      of vasculitis. Treatment of cryofibrinogenemia should be directed at the
      underlying disease process, if one can be found. Other treatments have included
      the anabolic steroid stanozolol, which is presently unavailable, anticoagulants,
      immunosuppressive agents, plasmapheresis, and the combination of streptokinase
      and streptodornase. We report a case of a 61-year-old male smoker with a 10-year
      history of intermittent ulcerations of both legs and feet. Two separate biopsies
      showed epidermal ulceration and thrombi within superficial dermal vessels without
      evidence of vasculitis. These findings, together with the presence of elevated
      plasma cryofibrinogen, led to the diagnosis of cryofibrinogenemia. The patient
      continued to have ulcerations despite efforts to control his high blood pressure,
      cold avoidance, local wound care, and treatment with pentoxifylline 800 mg three
      times daily. However, when colchicine 0.6 mg twice daily was added to the
      patient's care, this led to rapid healing of his ulcerations. He has remained
      ulcer free for 2 years taking the combination of colchicine and high-dose
      pentoxifylline. Efforts to reduce the dose of these agents have repeatedly led to
      recurrences, and remission has promptly followed re-establishment of the
      combination. To our knowledge, this is the first report documenting use of the
      combination of colchicine and high-dose pentoxifylline to successfully treat
      ulcers due to cryofibrinogenemia.

PMID- 19170412
TI  - Adalimumab: in plaque psoriasis.
AB  - Adalimumab is a recombinant, human, IgG1 monoclonal antibody specific for tumor
      necrosis factor. The clinical efficacy and safety of adalimumab (40 mg
      administered subcutaneously every other week) in patients with moderate-to-severe
      chronic plaque psoriasis have been demonstrated in several randomized, double
      blind clinical trials, including the pivotal trials REVEAL (n = 1212) and
      CHAMPION (n = 271). Based on these trials, adalimumab was significantly more
      effective than placebo and methotrexate at relieving the signs and symptoms of
      psoriasis after 16 weeks of treatment, as assessed by the percentage of patients
      achieving a 75% improvement from baseline in Psoriasis Area and Severity Index.
      Based on open-label extension studies of up to 2 years' duration, the efficacy of
      adalimumab was sustained over the long term. Of patients who had responded to 33
      weeks of treatment with adalimumab in REVEAL, patients randomized to remain on
      adalimumab for an additional 19 weeks of treatment were significantly less likely
      to experience loss of an adequate response than patients who were transferred to
      placebo. Compared with placebo or methotrexate, adalimumab was associated with
      significantly greater improvements in dermatology-specific and general measures
      of health-related quality of life in patients with plaque psoriasis. Adalimumab
      was generally well tolerated in trials in patients with plaque psoriasis, and the
      adverse-event profile was similar to that associated with its use in rheumatoid
      arthritis.

PMID- 19170413
TI  - Efalizumab: a review of its use in the management of chronic moderate-to-severe
      plaque psoriasis.
AB  - Efalizumab (Raptiva) is a recombinant, humanized, monoclonal antibody that
      targets CD11a, the alpha-subunit of the heterodimeric lymphocyte surface protein
      lymphocyte function-associated antigen-1 (LFA-1). It is approved for the
      treatment of adult patients (aged > or = 18 years) with chronic moderate-to
      severe plaque psoriasis who are candidates for systemic therapy or phototherapy
      (in the US), or who have failed to respond to, have a contraindication to, or are
      intolerant of, other systemic therapies, including cyclosporine (ciclosporin),
      methotrexate, and psoralen plus UVA photochemotherapy (in the EU). Weekly
      subcutaneous injections of efalizumab are effective and generally well tolerated
      in the treatment of adults with chronic moderate-to-severe plaque psoriasis,
      including high-need individuals (i.e. those for whom at least two currently
      available systemic therapies are unsuitable due to lack of efficacy, intolerance,
      or contraindication), and patients with difficult-to-treat forms of the disease
      affecting the scalp, hands/feet, or nails. Clinical improvements are maintained,
      with no evidence of cumulative or end-organ toxicity, during continuous
      administration of efalizumab for up to 3 years; 4-, 5-, and 7-year safety data
      are being collected. The therapeutic profile of efalizumab cannot be directly
      compared with that of other antipsoriasis agents because of a lack of head-to
      head comparative studies. Nonetheless, a considerable body of data indicates that
      efalizumab is an appropriate alternative to other biologic or nonbiologic
      therapies for the treatment of chronic moderate-to-severe plaque psoriasis that,
      additionally, offers the potential convenience of self-injection at home.

PMID- 19170414
TI  - Psychological growth among siblings of children with and without intellectual
      disabilities.
AB  - The presence of a child with an intellectual disability is often perceived as a
      cloud hanging over the heads of their siblings, placing them at risk of
      developing a variety of problems. Only recently have siblings been examined for
      the positive aspects of this life situation, such as the potential to experience
      psychological growth. Adopting J. A. Schaffer and G. H. Moos' (1992) theoretical
      framework, this study investigated the contribution of perceived stress, self
      differentiation, and parental preference to the personal, social, and spiritual
      growth of siblings. Participants comprised 101 siblings of children with
      intellectual disabilities and 89 siblings of children with typical development
      (age range = 13-19 years). Results indicated that siblings of children with
      intellectual disabilities evidence higher levels of growth, with self
      differentiation and perceived maternal preference acting as the main contributors
      to this growth.

PMID- 19170415
TI  - Are we there yet? Screening processes for intellectual and developmental
      disabilities in jail settings.
AB  - Early identification of intellectual and developmental disabilities in persons in
      the criminal justice system is essential to protect their rights during arrest
      and trial, ensure safety when incarcerated, and maximize the opportunities to
      receive services while incarcerated and postrelease. Using telephone interviews
      of jail administrators (N=80) in 1 state, this study examined how people with
      intellectual and developmental disabilities were identified in jails. Findings
      indicated that administrators varied widely in awareness of individuals with
      intellectual and developmental disabilities in their jails. Few jails (6%) used
      formal screening instruments for intellectual and developmental disabilities,
      others relied on officer observation and self-report (53%), and some provided no
      screening at all; in addition, officers received little training in this regard.
      Findings suggest that few jails are operationalizing best-practice screening
      processes for intellectual and developmental disabilities.

PMID- 19170416
TI  - Reliability of the Supports Intensity Scale (French version).
AB  - The definition of intellectual disability, according to the American Association
      on Intellectual and Developmental Disabilities, includes the assumption that
      adequate supports should improve a person's functioning. Consequently, support
      needs have to be assessed to plan services for persons with intellectual
      disability. The Supports Intensity Scale (SIS; J. R. Thompson et al., 2004) is a
      standardized instrument for assessing support needs and their intensity. This
      study was designed to estimate the interrespondent, interinterviewer coefficients
      of the French version of the SIS. Approximately 40 persons with intellectual
      disabilities from Quebec, a Canadian province, participated in this study. For
      each participant, 2 respondents and 2 interviewers were identified and 3 French
      SIS questionnaires were filled out. Results are presented and discussed compared
      with those obtained with the original, English-based SIS.

PMID- 19170417
TI  - Transition satisfaction and family well being among parents of young adults with
      severe intellectual disability.
AB  - The transition from high school to adulthood is a critical life stage that
      entails many changes, especially for youth with severe intellectual disability.
      The transition period may be especially stressful for the families of these young
      adults, who often experience a sudden change, or decrease, in services. However,
      little research has examined what constitutes a successful transition for the
      families of these individuals. The present study examined parent perspectives of
      transition for 128 young adults with severe intellectual disability,
      specifically, parent satisfaction with transition. Results suggested that
      transition satisfaction is related to young adult, family, and environmental
      characteristics, with environmental characteristics being the strongest
      predictors of transition satisfaction. Furthermore, transition satisfaction is
      related to multiple measures of family well being, indicating the tremendous need
      for considering the broader family system when planning for a young adult's
      transition. Implications and directions for future research are discussed.

PMID- 19170421
TI  - Left behind: health services and people with severe disabilities.

PMID- 19170422
TI  - Special education personnel utilization and general class placement of students
      with disabilities: ranges and ratios.

PMID- 19170425
TI  - Tapestry of memory.
AB  - In this essay, I have elaborated on the ideas and experiments that have guided my
      research career. First, I present my early research history and my involvement in
      determining the neurobiological basis of the consolidation process based
      primarily on the consolidation paradigm. Based on a series of experiments and a
      new interest in cognitive psychology, I then developed a cognitive and
      neurobiologically based model of memory. This model represents a comprehensive
      view of memory organization based on multiple processes and multiple forms of
      memory representation and is based on the neurobiology of a multiple attribute,
      multiple process, tripartite system model of memory. I present some detailed
      evidence in terms of the neural foundations, specific attributes, and processes
      of operation for the event-based, knowledge-based, and rule-based memory systems.
      In addition, I present a set of experiments to demonstrate that there might be
      parallel processing of mnemonic information in rats and humans. Finally, I
      recognize that ideas can be generated by reading the extant literature,
      interaction with colleagues at meetings, and exchange of ideas with students to
      design and execute hopefully meaningful experiments.

PMID- 19170426
TI  - Making time count: functional evidence for temporal coding of taste sensation.
AB  - Although the temporal characteristics of neural responses have been proposed as a
      mechanism for sensory neural coding, there has been little evidence thus far that
      this type of information is actually used by the nervous system. Here the authors
      show that patterned electrical pulses trains that mimic the response to the taste
      of quinine can produce a bitterlike sensation when delivered to the nucleus
      tractus solitarius of behaving rats. Following conditioned aversion training
      using either "quinine simulation" patterns of electrical stimulation or natural
      quinine (0.1 mM) as a conditioned stimulus, rats specifically generalized the
      aversion to 2 bitter tastants: quinine and urea. Randomization of the quinine
      simulation patterns resulted in generalization patterns that resembled those to a
      perithreshold concentration (0.01 mM) of quinine. These data provide strong
      evidence that the temporal pattern of brainstem activity may convey information
      about taste quality and underscore the functional significance of temporal
      coding.

PMID- 19170427
TI  - Multiple learning parameters differentially regulate olfactory generalization.
AB  - Sensory representations depend strongly on the descending regulation of
      perceptual processing. Generalization among similar stimuli is a fundamental
      cognitive process that defines the extent of the variance in physical stimulus
      properties that becomes categorized together and associated with a common
      contingency, thereby establishing units of meaning. The olfactory system provides
      an experimentally tractable model system in which to study the interactions of
      these physical and psychological factors within the framework of their underlying
      neurophysiological mechanisms. The authors here show that olfactory associative
      learning systematically regulates gradients of odor generalization. Specifically,
      increasing odor-reward pairings, odor concentration, or reward quality--each a
      determinant of associative learning--significantly transformed olfactory
      generalization gradients, each narrowing the range of variance in odor quality
      perceived as likely to share the learned contingency of a conditioned odor
      stimulus. However, differences in the qualitative features of these three
      transformations suggest that these different determinants of learning are not
      necessarily theoretically interchangeable. These results demonstrate that odor
      representations are substantially shaped by experience and descending influences.

PMID- 19170428
TI  - A honeybee's ability to learn, recognize, and discriminate odors depends upon
      odor sampling time and concentration.
AB  - Animals sample sensory stimuli for longer periods when they must perform
      difficult discrimination tasks, implying that the brain's ability to represent
      stimuli improves as a function of time. Although it is true in other senses, few
      studies have examined whether increasing sampling time improves olfactory
      discrimination. In the experiments reported here, odor sampling time was
      controlled with the goal of testing whether odor concentration affected a
      honeybee's ability to learn, recognize, and discriminate odors. Increasing
      sampling time during conditioning and testing improved a honeybee's ability to
      learn, recognize, and differentiate low-concentration (0.0002 M) odors. For
      intermediate-concentration (0.02 M) odors, both acquisition and recognition
      improved when stimulus duration was longer, but discrimination was unaffected.
      Having longer to sample a high-concentration (2.0 M) stimulus also improved
      acquisition, but it did not affect the ability to recognize or differentiate
      odors. Differences in time to respond to the conditioned and novel odors during
      the test period depended on the difficulty of the discrimination task. The
      results suggest that the sensory coding of molecular identity takes longer for
      low-concentration odors.

PMID- 19170429
TI  - NMDA receptor involvement in spatial delayed alternation in developing rats.
AB  - Two experiments examined the effect of the noncompetitive NMDA receptor
      antagonist, dizocilpine maleate (MK-801), on spatial working memory during
      development. Rats were trained on spatial delayed alternation (SDA) in a T-maze
      after ip administration of 0.06 mg/kg MK-801, 0.1 mg/kg MK-801, or saline on
      postnatal days (P) P23 and P33 (Experiment 1), or following bilateral
      intrahippocampal administration of 2.5 or 5.0 microg per side MK-801 or saline on
      P26 (Experiment 2). In Experiment 1, MK-801 dose-dependently impaired SDA
      learning at both ages. Because the same doses of systemic MK-801 have no effect
      on T-maze position discrimination learning, impairment of SDA by MK-801 likely
      reflects disruption of spatial working memory. Both doses of MK-801 abolished
      acquisition of SDA performance in Experiment 2. Disruption of hippocampal
      plasticity may account for the effects produced by systemic MK-801
      administration. These results confirm and extend earlier lesion studies by
      implicating plasticity of hippocampal neurons in the ontogeny of spatial delayed
      alternation.

PMID- 19170430
TI  - The role of the cerebellar interpositus nucleus in short and long term memory for
      trace eyeblink conditioning.
AB  - In previous studies the cerebellar interpositus (IP) nucleus, but not the
      hippocampus, was shown to be necessary both for initial learning and retention
      and for long-term retention of the standard delay eyeblink conditioned response
      (CR). However, in the trace eyeblink CR procedure, the hippocampus is also
      necessary for initial learning and retention, but not for long-term retention.
      Here the authors evaluate the role of the IP nucleus in both initial learning and
      retention, and in long-term retention of the trace eyeblink CR, using muscimol
      infusion to reversibly inactivate the IP nucleus. For the short-term study, there
      were two subgroups, the first sequentially passed through acquisition,
      inactivation, and reacquisition phases, whereas the second subgroup went through
      inactivation, acquisition, and inactivation phases. For the long-term study, the
      rabbits acquired the CR and then rested for a month. Next, they were distributed
      into two subgroups: with or without retention training, and finally went through
      inactivation and reacquisition phases. The results showed that the prelearning IP
      nucleus inactivation prevented the acquisition of the trace CR, whereas the
      postlearning inactivation reversibly abolished the expression of both the short-
      and long-term CR.

PMID- 19170431
TI  - Eyeblink conditioning during an interstimulus interval switch in rabbits
      (Oryctolagus cuniculus) using picrotoxin to disrupt cerebellar cortical input to
      the interpositus nucleus.
AB  - The role of the cerebellar cortex in eyeblink classical conditioning remains
      unclear. Experimental manipulations that disrupt the normal function impair
      learning to various degrees, and task parameters may be important factors in
      determining the severity of impairment. This study examined the role of
      cerebellar cortex in eyeblink conditioning under conditioned
      stimulus?unconditioned stimulus intervals known to be optimal or nonoptimal for
      learning. Using infusions of picrotoxin to the interpositus nucleus of the rabbit
      cerebellum, the authors pharmacologically disrupted input from the cerebellar
      cortex while training with an interstimulus interval (ISI)-switch procedure. One
      group of rabbits (Oryctolagus cuniculus) was 1st trained with a 250-ms ISI
      (optimal) and then switched to a 750-ms ISI (nonoptimal). A 2nd group was trained
      in the opposite order. The most striking effect was that picrotoxin-treated
      rabbits initially trained with a 250-ms ISI learned comparably to controls, but
      those initially trained with a 750-ms ISI were severely impaired. These results
      suggest that functional input from cerebellar cortex becomes increasingly
      important for the interpositus nucleus to learn delay eyeblink conditioning as
      the ISI departs from an optimal interval.

PMID- 19170432
TI  - The effects of FG7142 on overexpectation of Pavlovian fear conditioning.
AB  - Six experiments studied the role of GABA-sub(A) receptor activation in expression
      of overexpectation of Pavlovian fear conditioning. After separate pairings of CSA
      and CSB with shock in Stage I, rats received pairings of the compound AB with
      shock in Stage II, producing overexpectation of fear. The expression of
      overexpectation was attenuated, in a dose-dependent manner, by the benzodiazepine
      partial inverse agonist FG7142. FG7142 had no effect on responding to a CS paired
      with a low magnitude US or a CS subjected to associative blocking. These results
      suggest that the negative prediction error generated during overexpectation
      training may impose a mask on fear rather than erasing the original fear
      learning. They support claims that overexpectation shares features with
      extinction.

PMID- 19170433
TI  - Reactivity to visual signals and the cerebellar vermis: Evidence from a rare case
      with rhombencephalosynapsis.
AB  - The modulatory role of the cerebellum was investigated in a case with
      rhombencephalosynapsis (RS), a rare dysplasia characterized by the absence of the
      cerebellar vermis. The visual psychophysical task involved localizing a target
      and ignoring a distractor appearing either before, at the same time as, or after
      the target. It allowed us to assess reactivity to warning signals, distraction,
      and reactivity to signals appearing during attentive processing. Compared with a
      control sample, the patient exhibited greater reactivity to warning signals and
      difficulties interrupting attentive processing, whereas distraction was not
      increased. Complementary analyses showed that these deficits did not reflect just
      delayed development of attentional processes. These results suggest that the
      cerebellum modulates responsiveness and commands attentional/exploratory
      flexibility in response to sensory signals.

PMID- 19170435
TI  - Hippocampal involvement in the acquisition of relational associations, but not in
      the expression of a transitive inference task in mice.
AB  - The hippocampus (HC) has been suggested to play a role in transitive inference
      (TI) on an ordered sequence of stimuli. However, it has remained unclear whether
      HC is involved in the expression of TI, or rather contributes to TI through its
      role in the acquisition of the sequence of elements (Frank, Rudy, & O'Reilly,
      2003). Presently, the authors compared the effects of excitotoxic dorsal HC
      lesions in C57BL mice that received surgery before or after they were trained to
      discriminate between pairs of visual stimuli. Performance on a subsequent TI task
      was worse in mice with pretraining lesions than in those with posttraining
      lesions, which showed similar performance to shams without lesions. This
      indicates that HC is not involved in the expression of TI, but may merely help to
      acquire the underlying representations required for TI.

PMID- 19170434
TI  - Acquired appetitive responding to intravenous nicotine reflects a Pavlovian
      conditioned association.
AB  - Recent research examining Pavlovian appetitive conditioning has extended the
      associative properties of nicotine from the unconditioned stimulus or reward to
      include the role of a conditional stimulus (CS), capable of acquiring the ability
      to evoke a conditioned response. To date, published research has used presession
      extravascular injections to examine nicotine as a contextual CS in that
      appetitive Pavlovian drug discrimination task. Two studies in the current
      research examined whether a nicotine CS can function discretely, multiple times
      within a session using passive iv infusions. In Experiment 1, rats readily
      acquired a discrimination in conditioned responding between nicotine and saline
      infusions when nicotine was selectively paired with sucrose presentations. In
      Experiment 2, rats were either trained with nicotine paired with sucrose or
      explicitly unpaired with sucrose. The results showed that rats trained with
      explicitly unpaired nicotine and sucrose did not increase dipper entries after
      the infusions. Nicotine was required to be reliably paired with sucrose for
      control of conditioned responding to develop. Implications of these findings are
      discussed in relation to tobacco addiction, learning theory, and pharmacology.

PMID- 19170436
TI  - Magnitude of the object recognition deficit associated with perirhinal cortex
      damage in rats: Effects of varying the lesion extent and the duration of the
      sample period.
AB  - The present study examines 2 factors that might moderate the object-recognition
      deficit seen after perirhinal cortex damage. Object recognition by normal rats
      was improved by extending (from 4 to 8 min) the sample period during which an
      object was first explored. Furthermore, there was a significant positive
      correlation between time spent in close exploration of the sample object and
      degree of successful novelty discrimination. In contrast, rats with perirhinal
      cortex lesions failed to benefit from increased close exploration and did not
      discriminate the novel object after even the longest sample period. Nevertheless,
      the lesions did not disrupt habituation across repeated exposure to the same
      object. The second factor was extent of perirhinal cortex damage. A significant
      correlation was found between total perirhinal cortex loss and degree of
      recognition impairment. Within the perirhinal cortex, only damage to the caudal
      perirhinal cortex correlated significantly with recognition memory deficits. This
      study highlights the critical importance of the perirhinal cortex within the
      temporal lobe for recognition memory and shows that the lesion-induced deficit
      occurs despite seemingly normal levels of close object exploration.

PMID- 19170438
TI  - Posttrial corticosterone administration enhances the effects of incentive
      downshift: exploring the boundaries of this effect.
AB  - Posttrial administration of corticosterone was previously shown to enhance
      consummatory successive negative contrast (cSNC) in rats. The present series of
      experiments provides additional information that helps determine the boundaries
      of this effect. Posttrial corticosterone administration (1) enhances cSNC when
      rats experience a large downshift (32% to 4% sucrose), but not after a small
      downshift (8% to 4% sucrose; Experiment 1); (2) has no effect in an anticipatory
      negative contrast situation in which 4% sucrose precedes 32% sucrose in daily
      trials (Experiment 2); (3) does not support the development of a conditioned
      taste aversion to 4% sucrose, in the absence of an incentive downshift
      (Experiment 3); and (4) facilitates the extinction of consummatory behavior
      (Experiment 4). These results suggest that corticosterone facilitates the
      encoding of an egocentric aversive memory of the incentive downshift experience.

PMID- 19170437
TI  - Role of a lateralized parietal-basal ganglia circuit in hierarchical pattern
      perception: evidence from Parkinson's disease.
AB  - The role of corticostriatal circuits in hierarchical pattern perception was
      examined in Parkinson's disease. The hypothesis was tested that patients with
      right-side onset of motor symptoms (RPD, left hemisphere dysfunction) would be
      impaired at local level processing because the left posterior temporoparietal
      junction (TP) emphasizes processing of local information. By contrast, left-side
      onset patients (LPD; right hemisphere dysfunction) would show impaired global
      processing because right TP emphasizes global processing. Participants identified
      targets at local or global levels without and with attention biased toward those
      levels. Despite normal attentional control between levels, LPD patients showed a
      single dissociation, demonstrating abnormal global level processing under all
      conditions, whereas RPD patients showed abnormal local level processing mainly
      when attention was biased toward the local level. These findings link side of
      motor symptom onset to visuospatial cognitive abilities that depend upon the
      contralateral TP, highlighting that side of onset can predict visuospatial
      impairments, and provide evidence that an inferior parietal-basal ganglia pathway
      involving the caudate head and the hemispherically asymmetrical TP region is
      necessary for hierarchical pattern perception.

PMID- 19170439
TI  - Tegmental pedunculopontine glutamate and GABA-B synapses mediate morphine reward.
AB  - The tegmental pedunculopontine nucleus (TPP) of the midbrain is critical in
      mediating the acute rewarding effects of opiates. However, the circuitry and
      neurochemistry underlying this effect has not been determined. Here we identify
      TPP receptors and cell types involved in systemic morphine reward and suggest an
      anatomical and neurochemical model for reward in the TPP. Simple hypothetical
      anatomical models for serial cell arrangements and receptors in the TPP were
      proposed and predictions of behavioral outcome (reward or no reward) then were
      made, based on the administration of agonists and antagonists directly into the
      TPP of rats. We report that TPP-administered NMDA produced rewarding effects,
      although GABA agonists and antagonists had no motivational effects on their own.
      However, the NMDA receptor antagonist AP-7 and the GABA-B receptor antagonist
      saclofen, while having no motivational effects on their own, blocked systemic
      morphine reward as measured by conditioned place preference. These results
      provide positive evidence for GABA-B and glutamate synapses in the TPP, which
      mediates systemic morphine reward and suggest that a serial pathway for morphine
      reward in the TPP is unlikely.

PMID- 19170440
TI  - Strain differences in patterns of drug-intake during prolonged access to cocaine
      self-administration.
AB  - The current study examined possible interactions between genetic factors and
      prolonged drug access by testing the Fischer (F344), Lewis (LEW), and Wistar rat
      strains in a prolonged access cocaine self-administration (SA) procedure. Before
      prolonged access, the strains did not differ in breakpoints for food or cocaine
      with progressive ratio (PR) testing. The LEW and Wistar rats acquired cocaine SA
      faster than the F344s. With prolonged access to cocaine SA, the LEW and Wistar
      rats showed comparable within-session patterns that were higher at the outset of
      each session and decreased to a stable baseline. Alternatively, the F344 rats
      began sessions with lower intake and increased their rate of intake during the
      session. The F344 and Wistar rats took more drug per session than the LEW rats
      but did not differ from each other. Following prolonged access, the strains did
      not differ in breakpoints for food, but the Wistar rats had higher breakpoints
      for cocaine than the F344 rats. Possible underpinnings for the observed strain
      differences are discussed.

PMID- 19170441
TI  - Demand for food and cocaine in Fischer and Lewis rats.
AB  - Fischer and Lewis rat strains often serve as animal vulnerability models for drug
      abuse and addiction. When these strains respond for drugs of abuse, several
      measures, including total drug intake, response rate and progressive-ratio
      breakpoints, have been reported to be strain-dependent, a result suggesting
      genetic differences in drug reactivity and vulnerability. The present study
      extends these strain comparisons to a previously untested measure--demand
      analysis. In Experiment 1, four Fischer and four Lewis rats earned their daily
      food ration by lever pressing under a fixed-ratio schedule, the size of which was
      increased every three sessions from 3 to 1,000 in logarithmic steps. Consumption
      was plotted as a function of ratio size, and modeled by the exponential-demand
      equation (Hursh & Silberberg, 2008). Experiment 2 replicated Experiment 1 except
      that different rats were used, and cocaine reinforced lever pressing. A between
      experiment comparison showed a commodity-by-strain interaction: Fischer rats
      defended consumption with greater vigor when cocaine served as the reinforcer
      than did Lewis rats; for food, this relation was reversed. However, for both
      strains, defense of consumption of food exceeded that of cocaine.

PMID- 19170442
TI  - Naloxone and baclofen attenuate ethanol's locomotor-activating effects in
      preweanling Sprague-Dawley rats.
AB  - Heterogeneous rat strains appear to be particularly sensitive to the sedative
      effects of ethanol as adults and insensitive to ethanol's stimulant effects.
      Recently, the authors found that ethanol induces stimulant effects in preweanling
      Sprague-Dawley rats. In adult mice, these effects seem to be governed by the
      mesocorticolimbic dopaminergic pathway, which can be modulated by means of GABA B
      agonist (baclofen) or opioid antagonist (naloxone) treatments. This study tested
      whether these pharmacological treatments might reduce the activating effect of
      ethanol in preweanling Sprague-Dawley rats. Twelve-day-old pups given naloxone
      (Experiment 1A) or baclofen (Experiment 1B) before ethanol administration were
      tested in terms of locomotor activity in a novel environment. Naloxone and
      baclofen significantly reduced the stimulating effect of ethanol but had no
      effect on locomotor activity patterns in water-treated controls. Blood ethanol
      levels were not affected by naloxone or baclofen (Experiment 2). During the
      preweanling period, opioid and GABA B receptors seem to be involved in the
      stimulating effect of ethanol.

PMID- 19170443
TI  - Limited impact of social isolation on Alzheimer-like symptoms in a triple
      transgenic mouse model.
AB  - Gene-environment interactions are known to play a major role in the
      ethiopathology of several neuropsychiatric disorders, including Alzheimer's
      disease (AD). The present study investigates whether environmental manipulations,
      that is, social isolation, may affect the genetic predisposition to develop AD
      related traits in a triple transgenic mouse model (3 x Tg-AD), as suggested by
      our previous study employing physical exercise (Pietropaolo et al., 2008). Mutant
      and wild type mice of both sexes were housed singly or in groups from weaning,
      and evaluated behaviorally at 6 to 7 months of age. Independent of sex, the 3 x
      Tg-AD genotype was associated with enhanced acoustic startle response, improved
      performance in the cued version of the water maze and a clear impairment in the Y
      maze. Notably, the female (but not male) mutant mice showed increased anxiety.
      Although social isolation was effective in modifying several behaviors, it did
      not exacerbate any of the AD-like symptoms. Our findings demonstrated the
      differential susceptibility of the 3 x Tg-AD mouse line to environmental
      manipulations, showing that social isolation did not induce remarkable effects on
      the genetically determined AD-like symptoms, in contrast to what previously
      observed with physical exercise.

PMID- 19170444
TI  - An n-3 fatty acid deficiency impairs rat spatial learning in the Barnes maze.
AB  - In this study, the authors demonstrate that rats with n-3 fatty acid deficiency
      display spatial learning deficits in the Barnes circular maze. Dams were deprived
      of n-3 fatty acids during pregnancy and lactation, and their offspring were
      weaned to the same deficient diet. There was a 58% loss of brain docosahexaenoic
      acid (DHA) in the n-3 fatty acid-deficient rats in comparison to n-3 fatty acid
      adequate rats. At 8 weeks of age, deficient rats demonstrated moderate impairment
      in Barnes maze performance compared with the n-3 fatty acid-adequate rats during
      the initial training. In the reversal learning task, the n-3 fatty acid-deficient
      rats showed a profound deficit in performance: They required more time to find a
      new position of the escape tunnel, which was accompanied by a higher number of
      errors and perseverations. The n-3 fatty acid-deficient rats had reduced tissue
      levels of dopamine in the ventral striatum and enhanced levels of the metabolite
      3,4-dihydroxyphenylacetic acid in frontal cortex and hypothalamus. In summary,
      this study demonstrates that rats with low brain DHA have a deficit in spatial
      reversal learning that could be related to changes in dopamine transmission in
      critical brain circuits.

PMID- 19170445
TI  - Insular cortex lesions and morphine-induced suppression of conditioned stimulus
      intake in the rat.
AB  - The present experiment examined the influence of insular cortex (IC) lesions on
      the intake of a taste stimulus in a consummatory procedure that used morphine as
      the unconditioned stimulus. In normal rats, morphine caused a rapid reduction in
      saccharin intake when the taste was novel but not when it was familiar.
      Irrespective of stimulus novelty, morphine had little influence on the saccharin
      consumption of IC-lesioned rats. The results are discussed in terms of a lesion
      induced disruption of (i) a reward comparison mechanism and (ii) the perception
      of taste novelty.

PMID- 19170446
TI  - Scalar timing varies with response magnitude in classical conditioning of the
      nictitating membrane response of the rabbit (Oryctolagus cuniculus).
AB  - The present experiment was aimed at characterizing the timing of conditioned
      nictitating membrane (NM) movements as function of the interstimulus interval
      (ISI) in delay conditioning for rabbits (Oryctolagus cuniculus). Onset latency
      and peak latency were approximately, but not strictly, scalar for all but the
      smallest movements (<.10 mm). That is, both the mean and standard deviation of
      the timing measures increased in proportion to the ISI, but their coefficients of
      variation (standard deviation/mean) tended to be larger for shorter ISIs. For all
      ISIs, the absolute timing of the NM movements covaried with magnitude. The
      smaller movements (approximately, .11-.50 mm) were highly variable, and their
      peaks tended to occur well after the time of US delivery. The larger movements
      (>.50 mm) were less variable, and their peaks were better aligned with the time
      of US delivery. These results are discussed with respect to their implications
      for current models of timing in eyeblink conditioning.

PMID- 19170448
TI  - Behavioral deficits after distal focal cerebral ischemia in mice: Usefulness of
      adhesive removal test.
AB  - Distal occlusion of the middle cerebral artery (dMCAo), which closely mimics
      human stroke, is one of the most used animal models. However, although assessment
      of histological and functional outcome is increasingly recommended for
      preclinical studies, the latter is often excluded because of the high
      difficulties to estimate, especially in mice, behavioral impairments. The aim of
      our study was to deeply screen functional consequences of distal permanent MCAo
      in mice to target relevant behaviors for future studies. A set of sensorimotor
      and cognitive tests were performed during 3 weeks postsurgery in 2 groups of
      mice. Afterward, brain infarctions were estimated by histological staining or
      magnetic resonance imaging. Overall, while no long-term functional impairments
      could be detected, the adhesive removal was the only test showing a deficit.
      Interestingly, this sensorimotor impairment was correlated to cortical damage 3
      weeks after surgery. In conclusion, despite the fact that dMCAo-induced deficits
      could not be evidenced by most of our behavioral tests, the authors showed that
      the adhesive removal test was the only one, sensitive enough, to highlight a long
      term deficit. This result suggests therefore that this mouse model of ischemia is
      relevant to efficiently assess therapeutic strategies with histological but also
      behavioral analysis, provided that relevant tests are used.

PMID- 19170447
TI  - Peripheral delivery of a ROCK inhibitor improves learning and working memory.
AB  - Previously, utilizing a series of genome-wide association, brain imaging, and
      gene expression studies we implicated the KIBRA gene and the RhoA/ROCK pathway in
      hippocampal-mediated human memory. Here we show that peripheral administration of
      the ROCK inhibitor hydroxyfasudil improves spatial learning and working memory in
      the rodent model. This study supports the action of ROCK on learning and memory,
      suggests the potential value of ROCK inhibition for the promotion of cognition in
      humans, and highlights the powerful potential of unbiased genome-wide association
      studies to inform potential novel uses for existing pharmaceuticals.

PMID- 19170449
TI  - Parenting moderates a genetic vulnerability factor in longitudinal increases in
      youths' substance use.
AB  - The authors used a longitudinal, prospective design to investigate a moderation
      effect in the association between a genetic vulnerability factor, a variable
      nucleotide repeat polymorphism in the promoter region of 5HTT (5-HTTLPR), and
      increases in youths' substance use. The primary study hypothesis predicted that
      involved-supportive parenting would attenuate the link between the 5-HTTLPR
      polymorphism and longitudinal increases in substance use. African American youths
      residing in rural Georgia (N = 253, mean age = 11.5 years) provided 4 waves of
      data on their own substance use; the mothers of the youths provided data on their
      own parenting practices. Genetic data were obtained from youths via saliva
      samples. Latent growth curve modeling indicated that 5-HTTLPR status (presence of
      1 or 2 copies of the s allele) was linked with increases in substance use over
      time; however, this association was greatly reduced when youths received high
      levels of involved-supportive parenting. This study demonstrates that parenting
      processes have the potential to ameliorate genetic risk.

PMID- 19170450
TI  - Multidimensional family therapy for young adolescent substance abuse: twelve
      month outcomes of a randomized controlled trial.
AB  - Research has established the dangers of early onset substance use for young
      adolescents and its links to a host of developmental problems. Because critical
      developmental detours can begin or be exacerbated during early adolescence,
      specialized interventions that target known risk and protective factors in this
      period are needed. This controlled trial (n = 83) provided an experimental test
      comparing multidimensional family therapy (MDFT) and a peer group intervention
      with young teens. Participants were clinically referred, were of low income, and
      were mostly ethnic minority adolescents (average age = 13.73 years). Treatments
      were manual guided, lasted 4 months, and were delivered by community agency
      therapists. Adolescents and parents were assessed at intake, at 6-weeks post
      intake, at discharge, and at 6 and 12 months following treatment intake. Latent
      growth curve modeling analyses demonstrated the superior effectiveness of MDFT
      over the 12-month follow-up in reducing substance use (effect size: substance use
      frequency, d = 0.77; substance use problems, d = 0.74), delinquency (d = 0.31),
      and internalized distress (d = 0.54), and in reducing risk in family, peer, and
      school domains (d = 0.27, 0.67, and 0.35, respectively) among young adolescents.

PMID- 19170451
TI  - A randomized clinical trial of multisystemic therapy with juvenile sexual
      offenders: effects on youth social ecology and criminal activity.
AB  - A randomized clinical trial evaluated the efficacy of multisystemic therapy (MST)
      versus usual community services (UCS) for 48 juvenile sexual offenders at high
      risk of committing additional serious crimes. Results from multiagent assessment
      batteries conducted before and after treatment showed that MST was more effective
      than UCS in improving key family, peer, and academic correlates of juvenile
      sexual offending and in ameliorating adjustment problems in individual family
      members. Moreover, results from an 8.9-year follow-up of rearrest and
      incarceration data (obtained when participants were on average 22.9 years of age)
      showed that MST participants had lower recidivism rates than did UCS participants
      for sexual (8% vs. 46%, respectively) and nonsexual (29% vs. 58%, respectively)
      crimes. In addition, MST participants had 70% fewer arrests for all crimes and
      spent 80% fewer days confined in detention facilities than did their counterparts
      who received UCS. The clinical and policy implications of these findings are
      discussed.

PMID- 19170452
TI  - Randomized trial of group interventions to reduce HIV/STD risk and change
      theoretical mediators among detained adolescents.
AB  - Criminally involved adolescents engage in high levels of risky sexual behavior
      and alcohol use, and alcohol use may contribute to lack of condom use. Detained
      adolescents (n = 484) were randomized to (1) a theory-based sexual risk reduction
      intervention (GPI), (2) the GPI condition with a group-based alcohol risk
      reduction motivational enhancement therapy component (GPI + GMET), or (3) an
      information-only control (INFO). All interventions were presented in same-sex
      groups in single sessions lasting from 2 to 4 hr. Changes to putative theoretical
      mediators (attitudes, perceived norms, self-efficacy, and intentions) were
      measured immediately following intervention administration. The primary outcomes
      were risky sexual behavior and sexual behavior while drinking measured 3 months
      later (65.1% retention). The GPI + GMET intervention demonstrated superiority
      over both other conditions in influencing theoretical mediators and over the INFO
      control in reducing risky sexual behavior. Self-efficacy and intentions were
      significant mediators between condition and later risky sexual behavior. This
      study contributes to an understanding of harm reduction among high-risk
      adolescents and has implications for understanding circumstances in which the
      inclusion of GMET components may be effective.

PMID- 19170453
TI  - Internet-based personalized feedback to reduce 21st-birthday drinking: a
      randomized controlled trial of an event-specific prevention intervention.
AB  - This article presents an initial randomized controlled trial of an event-specific
      prevention intervention. Participants included 295 college students (41.69% male,
      58.31% female) who intended to consume 2 or more drinks on their 21st birthday.
      Participants completed a screening/baseline assessment approximately 1 week
      before they turned 21 and were randomly assigned to receive Web-based
      personalized feedback or assessment only. Feedback included normative
      information, protective behaviors, and personalized blood alcohol concentration
      information. A follow-up assessment was completed approximately 1 week after a
      student's birthday. Results indicated a significant intervention effect in
      reducing estimated blood alcohol concentration (d = 0.33). The intervention
      effect was moderated by 21st-birthday drinking intentions, and the intervention
      was primarily effective among those who intended to reach higher levels of
      intoxication. Results provide some support for normative information as a
      mediator of intervention efficacy. Overall results provide support for Web-based
      personalized feedback as an intervention approach for specific events associated
      with extreme drinking.

PMID- 19170454
TI  - Dismantling motivational interviewing and feedback for college drinkers: a
      randomized clinical trial.
AB  - Motivational interviewing (MI) is a counseling style that has been shown to
      reduce heavy drinking among college students. To date, all studies of MI among
      college students have used a format that includes a feedback profile delivered in
      an MI style. This study was a dismantling trial of MI and feedback among heavy
      drinking college students. After an initial screen, 279 heavy-drinking students
      were randomized to (a) Web feedback only, (b) a single MI session without
      feedback, (c) a single MI session with feedback, or (d) assessment only. At 6
      months, MI with feedback significantly reduced drinking, as compared with
      assessment only (effect size = .54), MI without feedback (effect size = .63), and
      feedback alone (effect size = .48). Neither MI alone nor feedback alone differed
      from assessment only. Neither sex, race or ethnicity, nor baseline severity of
      drinking moderated the effect of the intervention. Norm perceptions mediated the
      effect of the intervention on drinking. MI with feedback appears to be a robust
      intervention for reducing drinking and may be mediated by changes in normative
      perceptions.

PMID- 19170455
TI  - Computer versus in-person intervention for students violating campus alcohol
      policy.
AB  - In this study, the authors evaluated the efficacy of a brief motivational
      intervention (BMI) and a computerized program for reducing drinking and related
      problems among college students sanctioned for alcohol violations. Referred
      students (N = 198, 46% women), stratified by gender, were randomly assigned to a
      BMI or to the Alcohol 101 Plus computer program. Data obtained at baseline, 1, 6,
      and 12 months were used to evaluate intervention efficacy. Planned analyses
      revealed 3 primary findings. First, women who received the BMI reduced drinking
      more than did women who received the computer intervention; in contrast, men's
      drinking reductions did not differ by condition. Second, readiness to change and
      hazardous drinking status predicted drinking reductions at 1 month
      postintervention, regardless of intervention. Third, by 1 year, drinking returned
      to presanction (baseline) levels, with no differences in recidivism between
      groups. Exploratory analyses revealed an overall mean reduction in drinking
      immediately after the sanction event and before taking part in an intervention.
      Furthermore, after the self-initiated reductions prompted by the sanction were
      accounted for, participation in the BMI but not the computer intervention was
      found to produce additional reduction in drinking and related consequences.

PMID- 19170457
TI  - Maintenance of gains following experiential therapies for depression.
AB  - Follow-up data across an 18-month period are presented for 43 adults who had been
      randomly assigned and had responded to short-term client-centered (CC) and
      emotion-focused (EFT) therapies for major depression. Long-term effects of these
      short-term therapies were evaluated using relapse rates, number of asymptomatic
      or minimally symptomatic weeks, survival times across an 18-month follow-up, and
      group comparisons on self-report indices at 6- and 18-month follow-up among those
      clients who responded to the acute treatment phase. EFT treatment showed superior
      effects across 18 months in terms of less depressive relapse and greater number
      of asymptomatic or minimally symptomatic weeks, and the probability of
      maintaining treatment gains was significantly more likely in the EFT treatment
      than in the CC treatment. In addition, follow-up self-report results demonstrated
      significantly greater effects for EFT clients on reduction of depression and
      improvement of self-esteem, and there were trends in favor of EFT, in comparison
      with CC, on reduction of general symptom distress and interpersonal problems.
      Maintenance of treatment gains following an empathic relational treatment appears
      to be enhanced by the addition of specific experiential and gestalt-derived
      emotion-focused interventions. Clinical and theoretical implications of these
      findings are presented.

PMID- 19170456
TI  - Individual and situational factors that influence the efficacy of personalized
      feedback substance use interventions for mandated college students.
AB  - Little is known about individual and situational factors that moderate the
      efficacy of personalized feedback interventions (PFIs). Mandated college students
      (N = 348) were randomly assigned either to a PFI delivered in the context of a
      brief motivational interview (BMI; n = 180) or to a written PFI only (WF)
      condition and were followed up at 4 months and 15 months postintervention. The
      authors empirically identified heterogeneous subgroups utilizing mixture modeling
      analysis based on heavy episodic drinking and alcohol-related problems. The 4
      identified groups were dichotomized into an improved group (53.4%) and a
      nonimproved group (46.6%). Logistic regression results indicated that the BMI was
      no more efficacious than the WF across all mandated students. However, mandated
      students who experienced a serious incident requiring medical or police attention
      and those with higher levels of alcohol-related problems at baseline benefited
      more from the BMI than from the WF. It may be an efficacious and cost-effective
      approach to provide a written PFI for low-risk mandated students and an enhanced
      PFI with a BMI for those students who experience a serious incident or have
      higher baseline alcohol-related problems.

PMID- 19170458
TI  - Dynamic emotional processing in experiential therapy: two steps forward, one step
      back.
AB  - The study of dynamic and nonlinear change has been a valuable development in
      psychotherapy process research. However, little advancement has been made in
      describing how moment-by-moment affective processes contribute to larger units of
      change. The purpose of this study was to examine observable moment-by-moment
      sequences in emotional processing as they occurred within productive sessions of
      experiential therapy. This article further tested A. Pascual-Leone and L. S.
      Greenberg's (2007) model of emotional processing through a reanalysis of their
      data sample of 34 sessions in which clients presented with global distress: 17
      that ended in poor in-session events and 17 that ended in good in-session events.
      Current analyses used univariate and bootstrapping statistical methods to examine
      how dynamic temporal patterns in clients' emotion accumulated moment-by-moment to
      produce in-session gains in emotional processing. Results show that effective
      emotional processing was simultaneously associated with steady improvement
      according to the model as well as increased emotional range. Consequentially,
      good events were shown to occur in a 2-steps-forward, 1-step-back fashion.
      Finally, good events were also shown to have progressively shortened emotional
      collapses, whereas the opposite was true for poor in-session events.

PMID- 19170459
TI  - Childhood sexual abuse, stigmatization, internalizing symptoms, and the
      development of sexual difficulties and dating aggression.
AB  - Potential pathways from childhood sexual abuse (CSA) to subsequent romantic
      intimacy problems were examined in a prospective longitudinal study of 160
      ethnically diverse youth with confirmed CSA histories. Participants were
      interviewed at the time of abuse discovery, when they were 8-15 years of age, and
      again 1-6 years later. Stigmatization (abuse-specific shame and self-blame) and
      internalizing symptoms (posttraumatic stress and depressive symptoms), more than
      abuse severity, explained which youth with CSA histories experienced more sexual
      difficulties and dating aggression. Stigmatization was found to operate as a
      predictive mechanism for subsequent sexual difficulties. Internalizing symptoms
      were not predictive of romantic intimacy problems, although they did show
      correlational relations with sexual difficulties and dating aggression. Early
      interventions such as trauma-focused cognitive-behavioral therapy that target
      stigmatization may be important for preventing the development of sexual
      difficulties in CSA youth.

PMID- 19170461
TI  - Therapist-aided exposure for women with lifelong vaginismus: a replicated single
      case design.
AB  - Vaginismus is commonly described as a persistent difficulty in allowing vaginal
      entry of a penis or other object. Lifelong vaginismus occurs when a woman has
      never been able to have intercourse. A replicated single-case A-B-phase design
      was used to investigate the effectiveness of therapist-aided exposure for
      lifelong vaginismus. A baseline period (Phase A) was contrasted with exposure +
      follow-up (Phase B), using random switching between phases. The main outcome
      measure (intercourse ability) was assessed daily for 24 weeks. Ten women
      participated. The exposure consisted of a maximum of three 2-hr sessions during 1
      week at a university hospital. The participant performed vaginal penetration
      exercises on herself, in the presence of a female therapist. Two follow-up
      sessions were scheduled over a 5-week period. Nine of the 10 participants
      reported having intercourse after treatment, and in 5 of the 9, intercourse was
      possible within the 1st week of treatment. The results remained at 1-year follow
      up. Furthermore, exposure was successful in decreasing fear and negative
      penetration beliefs posttreatment and at 3-month and 1-year follow-ups. Therapist
      aided exposure appears to be an effective treatment for lifelong vaginismus.

PMID- 19170460
TI  - Trajectories of resilience, resistance, and distress during ongoing terrorism:
      the case of Jews and Arabs in Israel.
AB  - This is the 1st longitudinal examination of trajectories of resilience and
      resistance (rather than ill-being) among a national sample under ongoing threat
      of mass casualty. The authors interviewed a nationally representative sample of
      Jews and Arabs in Israel (N = 709) at 2 times during a period of terrorist and
      rocket attacks (2004-2005). The resistance trajectory, exhibiting few or no
      symptoms of traumatic stress and depression at both time points, was
      substantially less common (22.1%) than has previously been documented in studies
      following single mass casualty events. The resilience trajectory, exhibiting
      initial symptoms and becoming relatively nonsymptomatic, was evidenced by 13.5%
      of interviewees. The chronic distress trajectory was documented among a majority
      of participants (54.0%), and a small proportion of persons were initially
      relatively symptom-free but became distressed (termed delayed distress
      trajectory; 10.3%). Less psychosocial resource loss and majority status (Jewish)
      were the most consistent predictors of resistance and resilience trajectories,
      followed by greater socioeconomic status, greater support from friends, and less
      report of posttraumatic growth.

PMID- 19170462
TI  - Prediction of response to treatment in a randomized clinical trial of couple
      therapy: a 2-year follow-up.
AB  - Many studies have examined pretreatment predictors of immediate posttreatment
      outcome, but few studies have examined prediction of long-term treatment response
      to couple therapies. Four groups of predictors (demographic, intrapersonal,
      communication, and other interpersonal) and 2 moderators (pretreatment severity
      and type of therapy) were explored as predictors of clinically significant change
      measured 2 years after treatment termination. Results demonstrated that power
      processes and expressed emotional arousal were the strongest predictors of 2-year
      response to treatment. Moderation analyses showed that these variables predicted
      differential treatment response to traditional versus integrative behavioral
      couple therapy and that more variables predicted 2-year response for couples who
      were less distressed when beginning treatment. Findings are discussed with regard
      to existing work on prediction of treatment response, and directions for further
      study are offered.

PMID- 19170463
TI  - Citalopram intervention for hostility: results of a randomized clinical trial.
AB  - Hostility is associated with an increased risk for cardiovascular disease (CVD).
      Because central serotonin may modulate aggression, we might expect selective
      serotonin reuptake inhibitors (SSRIs) to be effective in reducing hostility. Such
      effects have never been examined in individuals scoring high on hostility who are
      otherwise free from major Axis I psychopathology according to criteria in the
      Diagnostic and Statistical Manual of Mental Disorders (4th ed., Text Revision;
      American Psychiatric Association, 2000). A total of 159 participants (ages 30?50
      years, 50% female) scoring high on 2 measures of hostility and with no current
      major Axis I diagnosis were randomly assigned to 2 months of citalopram (40 mg,
      fixed-flexible dose) or placebo. Adherence was assessed by electronic measurement
      and by drug exposure assessment. Treated participants showed larger reductions in
      state anger (Condition x Time; p = .01), hostile affect (p = 02), and, among
      women only, physical and verbal aggression (p = .005) relative to placebo
      controls. Treatment was also associated with relative increases in perceived
      social support (p = .04). The findings have implications for understanding the
      central nervous system correlates of hostility, its associations with other
      psychosocial risk factors for CVD, and, potentially, the design of effective
      interventions.

PMID- 19170464
TI  - Maternal attributions and child oppositional behavior: a longitudinal study of
      boys with and without attention-deficit/hyperactivity disorder.
AB  - The authors examined changes over a 1-year period in mothers' attributions for
      child behavior and child oppositional behavior among 53 mothers and nonproblem
      sons and 44 mothers and sons with attention-deficit/hyperactivity disorder
      (ADHD). Boys averaged 8 years of age (SD = 11 months) at Time 1. Families were
      primarily of European Canadian cultural background and most were middle to upper
      middle class. Initial levels of child oppositionality did not predict changes in
      mothers' attributions over time. However, initial levels of mothers' attributions
      of oppositional child behavior to internal, stable, and global causes positively
      predicted child oppositional behavior, controlling for ADHD versus nonproblem
      status and the child's initial level of oppositional behavior. Although initial
      levels of overreactive and nonresponsive parenting also positively predicted
      child oppositional behavior, the contribution of mothers' attributions remained
      significant even with parenting variables controlled. Results suggest that
      mothers' attributions of child oppositional behavior to internal, stable, and
      global causes may contribute to maintenance of child problems over time and that
      these parenting cognitions have importance as intervention targets.

PMID- 19170465
TI  - Psychosocial concerns of sexual minority youth: complexity and caution in group
      differences.
AB  - This investigation tested a large adolescent sample (n = 14,439) for significant
      group differences on psychosocial concerns on the basis of intersecting
      identities of sexual orientation (lesbian, gay, bisexual, questioning/less
      certain, heterosexual), race (Whites, racial minorities), and gender (boys,
      girls). A significant 2-way interaction between sexual orientation and gender was
      identified on victimization. Boys reported higher victimization than did girls
      among heterosexual and questioning/less certain students. Furthermore,
      significant 3-way interactions between sexual orientation, race, and gender were
      identified for substance use and depressed/suicidal thoughts. Questioning/less
      certain youth generally reported the highest levels of victimization, substance
      abuse, and suicidal thoughts. However, results suggest that, on the basis of
      small effect sizes for most comparisons, significant differences should be
      interpreted with caution. Results indicate the need to consider the diversity of
      subgroups within the sexual minority youth community and that intervention
      efforts might be more effective if tailored to the unique needs of specific
      subgroups.

PMID- 19170466
TI  - Attentional capture by salient color singleton distractors is modulated by top
      down dimensional set.
AB  - Three experiments examined whether salient color singleton distractors
      automatically interfere with the detection singleton form targets in visual
      search (e.g., J. Theeuwes, 1992), or whether the degree of interference is top
      down modulable. In Experiments 1 and 2, observers started with a pure block of
      trials, which contained either never a distractor or always a distractor (0% or
      100% distractors)--varying the opportunity to learn distractor suppression. In
      the subsequent trial blocks, the proportion of distractors was systematically
      varied (within-subjects factor in Experiment 1, between-subjects factor in
      Experiment 2)--varying the incentive to use distractor suppression. In Experiment
      3, observers started with 100% distractors in the first block and were presented
      with "rare" color or luminance distractors, in addition to "frequent" color
      distractors, in the second block. The results revealed distractor interference to
      vary as a function of both the initial experience with distractors and the
      incentive to suppress them: the interference was larger without relevant practice
      and with a lesser incentive to apply suppression (Experiments 1-3). This set of
      findings suggests that distractor interference is top-down modulable.

PMID- 19170467
TI  - Canonical views of dynamic scenes.
AB  - The visual recognition of dynamic scenes was examined. The authors hypothesized
      that the notion of canonical views, which has received strong empirical support
      for static objects, also holds for dynamic scenes. In Experiment 1, viewpoints
      orthogonal to the main axis of movement in the scene were preferred over other
      viewpoints, whereas viewpoints in line with the main axis were least preferred.
      Experiment 2 provided no empirical evidence for a recognition advantage of
      canonical viewpoints when presented during the initial learning phase, but
      Experiment 3 showed a cognitive advantage for canonical viewpoints if they were
      presented as test stimuli during the recognition test. Overall, the findings
      suggest that on a phenomenological level, viewers are consciously aware of such
      viewpoints, and, on a cognitive level, viewers benefit from canonical viewpoints
      in terms of recognition accuracy.

PMID- 19170468
TI  - Detecting and remembering simultaneous pictures in a rapid serial visual
      presentation.
AB  - Viewers can easily spot a target picture in a rapid serial visual presentation
      (RSVP), but can they do so if more than 1 picture is presented simultaneously? Up
      to 4 pictures were presented on each RSVP frame, for 240 to 720 ms/frame. In a
      detection task, the target was verbally specified before each trial (e.g., man
      with violin); in a memory task, recognition was tested after each sequence.
      Target detection was much better than recognition memory, but in both tasks the
      more pictures on the frame, the lower the performance. When the presentation
      duration was set at 160 ms with a variable interframe interval such that the
      total times were the same as in the initial experiments, the results were
      similar. The results suggest that visual processing occurs in 2 stages: fast,
      global processing of all pictures in Stage 1 (usually sufficient for detection)
      and slower, serial processing in Stage 2 (usually necessary for subsequent
      memory).

PMID- 19170469
TI  - Viewpoint and the recognition of people from their movements.
AB  - Observers can recognize other people from their movements. What is interesting is
      that observers are best able to recognize their own movements. Enhanced visual
      sensitivity to self-generated movement may reflect the contribution of motor
      planning processes to the visual analysis of human action. An alternative view is
      that enhanced visual sensitivity to self-motion results from extensive experience
      seeing one's own limbs move. To investigate this alternative explanation,
      participants viewed point-light actors from first-person egocentric and third
      person allocentric viewpoints. Although observers routinely see their own actions
      from the first-person view, participants were unable to identify egocentric views
      of their own actions. Conversely, with little real-world experience seeing
      themselves from third-person views, participants readily identified their own
      actions from allocentric views. When viewing allocentric displays, participants
      accurately identified both front and rear views of their own actions. Because
      people have little experience observing themselves from behind or from third
      person views, these findings suggest that visual learning cannot account for
      enhanced visual sensitivity to self-generated action.

PMID- 19170470
TI  - Semantic contextual cuing and visual attention.
AB  - Since M. M. Chun and Y. Jiang's (1998) original study, a large body of research
      based on the contextual cuing paradigm has shown that the visuocognitive system
      is capable of capturing certain regularities in the environment in an implicit
      way. The present study investigated whether regularities based on the semantic
      category membership of the context can be learned implicitly and whether that
      learning depends on attention. The contextual cuing paradigm was used with
      lexical displays in which the semantic category of the contextual words either
      did or did not predict the target location. Experiments 1 and 2 revealed that
      implicit contextual cuing effects can be extended to semantic category
      regularities. Experiments 3 and 4 indicated an implicit contextual cuing effect
      when the predictive context appeared in an attended color but not when the
      predictive context appeared in an ignored color. However, when the previously
      ignored context suddenly became attended, it immediately facilitated performance.
      In contrast, when the previously attended context suddenly became ignored, no
      benefit was observed. Results suggest that the expression of implicit semantic
      knowledge depends on attention but that latent learning can nevertheless take
      place outside the attentional field.

PMID- 19170471
TI  - The effect of occlusion on motion integration in infants.
AB  - Previous psychophysical studies have shown that the adult human visual system
      makes use of form information such as occlusion to determine whether to integrate
      or segregate local motion signals (J. McDermott, Y. Weiss, & E. H. Adelson,
      2001). Using the displays developed by McDermott et al., these experiments
      examined whether occlusion and amodal completion affect motion integration in
      infants. After familiarizing infants with the displays, infants were tested for
      preference between coherent motion and local motion displays. The results
      indicate that 5- to 8-month-olds, but not 3-month-olds, showed a significantly
      greater preference for the local motion display under occlusion conditions. These
      results suggest that 5- to 8-month-olds perceive motion to be coherent under
      occlusion conditions. The results are compatible with previous data showing that
      amodal completion of static information emerges at around 5-6 months of age (Y.
      Otsuka et al., 2006a), adding that infants use amodal completion for motion
      integration at this same time.

PMID- 19170472
TI  - Layout geometry in encoding and retrieval of spatial memory.
AB  - Two experiments investigated whether the spatial reference directions that are
      used to specify objects' locations in memory can be solely determined by layout
      geometry. Participants studied a layout of objects from a single viewpoint while
      their eye movements were recorded. Subsequently, participants used memory to make
      judgments of relative direction (e.g., "Imagine you are standing at X, facing Y,
      please point to Z"). When the layout had a symmetric axis that was different from
      participants' viewing direction, the sequence of eye fixations on objects during
      learning and the preferred directions in pointing judgments were both determined
      by the direction of the symmetric axis. These results provide further evidence
      that interobject spatial relations are represented in memory with intrinsic
      frames of reference.

PMID- 19170474
TI  - Gaze perception requires focused attention: evidence from an interference task.
AB  - The direction of another person's gaze is difficult to ignore when presented at
      the center of attention. In 6 experiments, perception of unattended gaze was
      investigated. Participants made directional (left-right) judgments to gazing-face
      or pointing-hand targets, which were accompanied by a distractor face or hand.
      Processing of the distractor was assessed via congruency effects on target
      response times. Congruency effects were found from the direction of distractor
      hands but not from the direction of distractor gazes (Experiment 1). This pattern
      persisted even when distractor sizes were increased to compensate for their
      peripheral presentation (Experiments 2 and 5). In contrast, congruency effects
      were exerted by profile heads (Experiments 3 and 4). In Experiment 6, isolated
      eye region distractors produced no congruency effects, even when they were
      presented near the target. These results suggest that, unlike other facial
      information, gaze direction cannot be perceived outside the focus of attention.

PMID- 19170473
TI  - A visual short-term memory advantage for objects of expertise.
AB  - Visual short-term memory (VSTM) is limited, especially for complex objects. Its
      capacity, however, is greater for faces than for other objects; this advantage
      may stem from the holistic nature of face processing. If the holistic processing
      explains this advantage, object expertise--which also relies on holistic
      processing--should endow experts with a VSTM advantage. The authors compared VSTM
      for cars among car experts and car novices. Car experts, but not car novices,
      demonstrated a VSTM advantage similar to that for faces; this advantage was
      orientation specific and was correlated with an individual's level of car
      expertise. Control experiments ruled out accounts based solely on verbal- or long
      term memory representations. These findings suggest that the processing
      advantages afforded by visual expertise result in domain-specific increases in
      VSTM capacity, perhaps by allowing experts to maximize the use of an inherently
      limited VSTM system.

PMID- 19170475
TI  - Feature integration theory revisited: dissociating feature detection and
      attentional guidance in visual search.
AB  - In feature integration theory (FIT; A. Treisman & S. Sato, 1990), feature
      detection is driven by independent dimensional modules, and other searches are
      driven by a master map of locations that integrates dimensional information into
      salience signals. Although recent theoretical models have largely abandoned this
      distinction, some observed results are difficult to explain in its absence. The
      present study measured dimension-specific performance during detection and
      localization, tasks that require operation of dimensional modules and the master
      map, respectively. Results showed a dissociation between tasks in terms of both
      dimension-switching costs and cross-dimension attentional capture, reflecting a
      dimension-specific nature for detection tasks and a dimension-general nature for
      localization tasks. In a feature-discrimination task, results precluded an
      explanation based on response mode. These results are interpreted to support
      FIT's postulation that different mechanisms are involved in parallel and focal
      attention searches. This indicates that the FIT architecture should be adopted to
      explain the current results and that a variety of visual attention findings can
      be addressed within this framework.

PMID- 19170476
TI  - The bicycle illusion: sidewalk science informs the integration of motion and
      shape perception.
AB  - The authors describe a new visual illusion first discovered in a natural setting.
      A cyclist riding beside a pair of sagging chains that connect fence posts appears
      to move up and down with the chains. In this illusion, a static shape (the
      chains) affects the perception of a moving shape (the bicycle), and this
      influence involves assimilation (averaging) rather than opposition
      (differentiation). These features distinguish the illusion from illusions of
      motion capture and induced motion. The authors take this bicycle illusion into
      the laboratory and report 4 findings: Naive viewers experience the illusion when
      discriminating horizontal from sinusoidal motion of a disc in the context of
      stationary curved lines; the illusion shifts from motion assimilation to motion
      opposition as the visual size of the display is increased; the assimilation and
      opposition illusions are dissociated by variations in luminance contrast of the
      stationary lines and the moving disc; and the illusion does not occur when simply
      comparing two stationary objects at different locations along the curved lines.
      The bicycle illusion provides a unique opportunity for studying the interactions
      between shape and motion perception.

PMID- 19170477
TI  - Selection difficulty and interitem competition are independent factors in rapid
      visual stream perception.
AB  - When observers try to identify successive targets in a visual stream at a rate of
      100 ms per item, accuracy for the 2nd target is impaired for intertarget lags of
      100-500 ms. Yet, when the same stream is presented more rapidly (e.g., 50 ms per
      item), this pattern reverses and a 1st-target deficit is obtained. M. C. Potter,
      A. Staub, and D. H. O'Connor (2002) accounted for these findings with a 2-stage
      competition theory (detection followed by identification) in which each stage is
      limited by its own pool of resources. In 5 experiments we varied the items that
      preceded the 1st target. The results show strong influences of these leading
      items on the 1st-target deficit, with almost no influence on 2nd-target accuracy.
      This is interpreted as strong support for multiple factors influencing target
      accuracy in rapid visual streams

PMID- 19170478
TI  - Unmasking the attentional blink.
AB  - When asked to identify 2 visual targets (T1 and T2 for the 1st and 2nd targets,
      respectively) embedded in a sequence of distractors, observers will often fail to
      identify T2 when it appears within 200-500 ms of T1--an effect called the
      attentional blink. Recent work shows that attention does not blink when the task
      is to encode a sequence of consecutive targets, suggesting that distractor
      interference plays a causal role in the attentional blink. Here, however, the
      authors show that an attentional blink occurs even in the absence of distractors,
      with 2 letter targets separated by a blank interval. In addition, the authors
      found that the impairment for identification of the 2nd of 2 targets separated by
      a blank interval is substantially attenuated either when the intertarget interval
      is filled with additional target items or when the 2nd target is precued by an
      additional target. These findings show that the root cause of the blink lies in
      the difficulty of engaging attention twice within a short period of time for 2
      temporally discrete target events.

PMID- 19170480
TI  - (De)stabilization of required and spontaneous postural dynamics with learning.
AB  - The present research examined how learning a new ankle-hip coordination
      influenced the preexisting postural repertoire. Standing participants learned a
      new ankle-hip coordination mode (relative phase of 90'). Before and after
      practice, postural patterns were evaluated in two different tasks. In the
      required task, specific ankle-hip patterns were requested (12 relative phases in
      multiples of 30'). In the spontaneous task, participants performed a tracking
      task in which no instructions about ankle-hip coordination were given. Learning
      induced changes in both required and spontaneous coordination dynamics. When
      ankle-hip patterns were required, learning led to improvement and homogenization
      in performance over the entire postural repertoire. When ankle-hip patterns
      emerged spontaneously, in-phase and antiphase preexisting patterns destabilized
      and changed toward the learned pattern of 90'. These findings demonstrate that
      learning a new coordination pattern can induce modifications of patterns that
      have not been practiced. The results also suggest that the consequences of
      learning do not generalize across different types of tasks, even when similar
      coordination modes are involved. We discuss implications of these findings for
      the generality of learning mechanisms.

PMID- 19170481
TI  - Contributions of procedure and stimulus learning to early, rapid perceptual
      improvements.
AB  - Improvements in performance on many perceptual skills can occur with only a
      single training session. Of interest here is what aspects of the training
      experience are being learned during this brief exposure. Although there is
      considerable evidence that learning associated with specific feature values of
      the stimulus used in training (stimulus learning) contributes to these rapid
      improvements, there has been little direct investigation of the possibility that
      other types of learning do so as well. Here the authors show that not only
      stimulus learning but also learning of more general aspects of the training
      experience (procedure learning) contributed to rapid improvements in performance
      on interaural time difference discrimination. However, practice on the type of
      judgment to be made did not appear to aid performance (no task learning). These
      results are consistent with physiological reports that different neural
      mechanisms are engaged at different time points during even a brief training
      session, and imply that the circuits that are engaged and likely modified vary in
      the degree of their selectivity to the target condition. Such changes presumably
      enable further learning.

PMID- 19170482
TI  - Flexible visual statistical learning: transfer across space and time.
AB  - The environment contains considerable information that is distributed across
      space and time, and the visual system is remarkably sensitive to such information
      via the operation of visual statistical learning (VSL). Previous VSL studies have
      focused on establishing what kinds of statistical relationships can be learned
      but have not fully explored how this knowledge is then represented in the mind.
      These representations could faithfully reflect the details of the learning
      context, but they could also be generalized in various ways. This was studied by
      testing how VSL transfers across changes between learning and test, and the
      results revealed a substantial degree of generalization. Learning of
      statistically defined temporal sequences was expressed in static spatial
      configurations, and learning of statistically defined spatial configurations
      facilitated detection performance in temporal streams. Learning of temporal
      sequences even transferred to reversed temporal orders during test when accurate
      performance did not depend on order, per se. These types of transfer imply that
      VSL can result in flexible representations, which may in turn allow VSL to
      function in ever-changing natural environments.

PMID- 19170483
TI  - Subjective patterns of randomness and choice: some consequences of collective
      responses.
AB  - Any individual's response intended to be random should be as probable as any
      other. However, 3 experiments show that many people's independent responses
      depart from the expected chance distribution. Participants responding to
      instructions of chance and related concepts favor the available options unequally
      in a similar way. Consequently, in hide-and-seek games, hiders converge on
      certain locations and are thereby detected beyond chance by seekers who share
      their preferences. People agree on salient and on nonsalient options, both of
      which are preferred under different instructions and even in the absence of
      instructions. Group responses strongly correlate under diverse, even opposing
      (e.g., competitive and cooperative) directions. Apparently, common default
      tendencies, combining random and aesthetic choices, are only somewhat modified
      under specific instructions. Maximal agreement with others is obtained through
      one's own aesthetic choices. Hence, implementing one's personal aesthetic
      preferences succeeds in matching others' choices even better than deliberate
      mutual coordination efforts. These results broadly replicate in 1- and 2
      dimensional tasks. Implications of the findings, their possible roots, and their
      connection to constructs from, e.g., game theory and subjective-complexity
      research, are discussed.

PMID- 19170484
TI  - Adaptive sex differences in auditory motion perception: looming sounds are
      special.
AB  - In 4 experiments, the authors examined sex differences in audiospatial perception
      of sounds that moved toward and away from the listener. Experiment 1 showed that
      both men and women underestimated the time-to-arrival of full-cue looming sounds.
      However, this perceptual bias was significantly stronger among women than among
      men. In Experiment 2, listeners estimated the terminal distance of sounds that
      approached but stopped before reaching them. Women perceived the looming sounds
      as closer than did men. However, in Experiment 3, with greater statistical power,
      the authors found no sex difference in the perceived distance of sounds that
      traveled away from the listener, demonstrating a sex-based specificity for
      auditory looming perception. Experiment 4 confirmed these results using
      equidistant looming and receding sounds. The findings suggest that sex
      differences in auditory looming perception are not due to general differences in
      audiospatial ability, but rather illustrate the environmental salience and
      evolutionary importance of perceiving looming objects.

PMID- 19170485
TI  - Audiovisual bounce-inducing effect: attention alone does not explain why the
      discs are bouncing.
AB  - Two discs moving from opposite points in space, overlapping and stopping at the
      other disc's starting point, can be seen as either bouncing or streaming through
      each other. With silent displays, observers report the discs as streaming,
      whereas if a sound is played when the discs touch each other, observers report
      the discs as bouncing. The origin of the switch from streaming to bouncing
      response is not known yet. The sound either shifts perception toward that of an
      impact-elastic event (i.e., a bounce) or subtracts the attention that is
      necessary to perceive the discs as streaming. We used either impact-similar
      (abrupt amplitude attack, gradual decay) or impact-dissimilar sounds (gradual
      amplitude attack, abrupt decay) and found that the first sounds induce the
      bouncing response, whereas the latter, although as distracting as the first,
      render streaming and bouncing responses equally frequent at most. We interpret
      the audiovisual bouncing effect as resulting from attention subtraction, which
      raises the number of bounce responses in comparison with silent displays, and
      from perception, which further increments the number of bounce responses and
      turns the response into a strong bounce response.

PMID- 19170486
TI  - Processing reduced word-forms in speech perception using probabilistic knowledge
      about speech production.
AB  - Two experiments examined how Dutch listeners deal with the effects of connected
      speech processes, specifically those arising from word-final /t/ reduction (e.g.,
      whether Dutch [tas] is tas, bag, or a reduced-/t/ version of tast, touch). Eye
      movements of Dutch participants were tracked as they looked at arrays containing
      4 printed words, each associated with a geometrical shape. Minimal pairs (e.g.,
      tas/tast) were either both above (boven) or both next to (naast) different
      shapes. Spoken instructions (e.g., "Klik op het woordje tas boven de ster,"
      [Click on the word bag above the star]) thus became unambiguous only on their
      final words. Prior to disambiguation, listeners' fixations were drawn to /t/
      final words more when boven than when naast followed the ambiguous sequences.
      This behavior reflects Dutch speech-production data: /t/ is reduced more before
      /b/ than before /n/. We thus argue that probabilistic knowledge about the effect
      of following context in speech production is used prelexically in perception to
      help resolve lexical ambiguities caused by continuous-speech processes.

PMID- 19170487
TI  - The role of accent salience and joint accent structure in meter perception.
AB  - Previous research indicates that temporal accents (TAs; accents due to time
      changes) play a strong role in meter perception, but evidence favoring a role for
      melodic accents (MAs; accents due to pitch changes) is mixed. The authors claim
      that this mixed support for MAs is the result of a failure to control for accent
      salience and addressed this hypothesis in Experiment 1. Listeners rated the
      metrical clarity of 13-tone melodies in which the magnitude and pattern of MAs
      and TAs were varied. Results showed that metrical clarity increased with both MA
      and TA magnitude. In Experiment 2, listeners were asked to rate metrical clarity
      in melodies with combinations of MA and TA patterns to allow the authors to
      ascertain whether these two accent types combined additively or interactively in
      meter perception. With respect to the additive or interactive debate, the
      findings highlighted the importance of (a) accent salience, (b) scoring methods,
      and (c) conceptual versus statistical interpretations of data. Implications for
      dynamic attending and neuropsychological investigations are discussed.

PMID- 19170488
TI  - Exposure influences expressive timing judgments in music.
AB  - This study is concerned with the question whether, and to what extent, listeners'
      previous exposure to music in everyday life, and expertise as a result of formal
      musical training, play a role in making expressive timing judgments in music.
      This was investigated by using a Web-based listening experiment in which
      listeners with a wide range of musical backgrounds were asked to compare 2
      recordings of the same composition (15 pairs, grouped in 3 musical genres), 1 of
      which was tempo-transformed (manipulating the expressive timing). The results
      show that expressive timing judgments are not so much influenced by expertise
      levels, as is suggested by the expertise hypothesis, but by exposure to a certain
      musical idiom, as is suggested by the exposure hypothesis. As such, the current
      study provides evidence for the idea that some musical capabilities are acquired
      through mere exposure to music, and that these abilities are more likely enhanced
      by active listening (exposure) than by formal musical training (expertise).

PMID- 19170489
TI  - Exploring auditory saltation using the "reduced-rabbit" paradigm.
AB  - Sensory saltation is a spatiotemporal illusion in which the judged positions of
      stimuli are shifted toward subsequent stimuli that follow closely in time. So
      far, studies on saltation in the auditory domain have usually employed subjective
      rating techniques, making it difficult to exactly quantify the extent of
      saltation. In this study, temporal and spatial properties of auditory saltation
      were investigated using the "reduced-rabbit" paradigm and a direct-location
      method. In 3 experiments, listeners judged the position of the 2nd sound within
      sequences of 3 short sounds by using a hand pointer. When the delay between the
      2nd and 3rd sound was short, the target sound was shifted toward the subsequent
      sound. The magnitude of displacement increased when the temporal and spatial
      distance between the sounds was reduced. In a 4th experiment, a modified reduced
      rabbit paradigm was used to test the hypothesis that auditory saltation is
      associated with an impairment of target sound localization. The findings are
      discussed with regard to a spatiotemporal integration approach in which the
      processing of auditory information is combined with information from subsequent
      stimuli.

PMID- 19170490
TI  - Facile synthesis of highly stable gold nanoparticles and their unexpected
      excellent catalytic activity for Suzuki-Miyaura cross-coupling reaction in water.
AB  - We have demonstrated that poly(2-aminothiophenol)-stablized gold nanoparticles
      with proper gold size and polymer thickness are active catalysts for Suzuki
      Miyaura cross-coupling reaction of aryl halides with arylboronic acids in water
      and air for the first time. High yields can be obtained with aryl halides or
      arylboronic acids bearing a variety of substituents. This new finding will
      undoubtedly broaden the application of gold nanoparticles in organic catalytic
      reactions.

PMID- 19170491
TI  - Noncooperative Formation of the off-pathway molten globule during folding of the
      alpha-beta parallel protein apoflavodoxin.
AB  - During folding of many proteins, molten globules are formed. These partially
      folded forms of proteins have a substantial amount of secondary structure but
      lack virtually all tertiary side-chain packing characteristic of native
      structures. Molten globules are ensembles of interconverting conformers and are
      prone to aggregation, which can have detrimental effects on organisms.
      Consequently, molten globules attract considerable attention. The molten globule
      that is observed during folding of flavodoxin from Azotobacter vinelandii is a
      kinetically off-pathway species, as it has to unfold before the native state of
      the protein can be formed. This intermediate contains helices and can be
      populated at equilibrium using guanidinium hydrochloride as denaturant, allowing
      the use of NMR spectroscopy to follow molten globule formation at the residue
      level. Here, we track changes in chemical shifts of backbone amides, as well as
      disappearance of resonances of unfolded apoflavodoxin, upon decreasing denaturant
      concentration. Analysis of the data shows that structure formation within
      virtually all parts of the unfolded protein precedes folding to the molten
      globule state. This folding transition is noncooperative and involves a series of
      distinct transitions. Four structured elements in unfolded apoflavodoxin
      transiently interact and subsequently form the ordered core of the molten
      globule. Although hydrophobic, tryptophan side chains are not involved in the
      latter process. This ordered core is gradually extended upon decreasing
      denaturant concentration, but part of apoflavodoxin's molten globule remains
      random coil in the denaturant range investigated. The results presented here,
      together with those reported on the molten globule of alpha-lactalbumin, show
      that helical molten globules apparently fold in a noncooperative manner.

PMID- 19170492
TI  - High lipophilicity of perfluoroalkyl carboxylate and sulfonate: implications for
      their membrane permeability.
AB  - Here we report on remarkably high lipophilicity of perfluoroalkyl carboxylate and
      sulfonate. A lipophilic nature of this emerging class of organic pollutants has
      been hypothesized as an origin of their bioaccumulation and toxicity. Both
      carboxylate and sulfonate, however, are considered hydrophilic while
      perfluroalkyl groups are not only hydrophobic but also oleophobic. Partition
      coefficients of a homologous series of perfluoroalkyl and alkyl carboxylates
      between water and n-octanol were determined as a measure of their lipophilicity
      by ion-transfer cyclic voltammetry. Very similar lipophilicity of perfluoroalkyl
      and alkyl chains with the same length is demonstrated experimentally for the
      first time by fragment analysis of the partition coefficients. This finding is
      important for pharmaceutical and biomedical applications of perfluoroalkyl
      compounds. Interestingly, approximately 2 orders of magnitude higher
      lipophilicity of a perfluoroalkyl carboxylate or sulfonate in comparison to its
      alkyl counterpart is ascribed nearly exclusively to their oxoanion groups. The
      higher lipophilicity originates from a strong electron-withdrawing effect of the
      perfluoroalkyl group on the adjacent oxoanion group, which is weakly hydrated to
      decrease its hydrophilicity. In fact, the inductive effect is dramatically
      reduced for a fluorotelomer with an ethylene spacer between perfluorohexyl and
      carboxylate groups, which is only as lipophilic as its alkyl counterpart,
      nonanoate, and is 400 times less lipophilic than perfluorononanoate. The high
      lipophilicity of perfluoroalkyl carboxylate and sulfonate implies that their
      permeation across such a thin lipophilic membrane as a bilayer lipid membrane is
      limited by their transfer at a membrane/water interface. The limiting
      permeability is lower and less dependent on their lipophilicity than the
      permeability controlled by their diffusion in the membrane interior as assumed in
      the classical solubility-diffusion model.

PMID- 19170493
TI  - Gene regulation with polyvalent siRNA-nanoparticle conjugates.
AB  - We report the synthesis and characterization of polyvalent RNA-gold nanoparticle
      conjugates (RNA-Au NPs), nanoparticles that are densely functionalized with
      synthetic RNA oligonucleotides and designed to function in the RNAi pathway. The
      particles were rationally designed and synthesized to be free of degrading
      enzymes, have a high surface loading of siRNA duplexes, and contain an auxiliary
      passivating agent for increased stability in biological media. The resultant
      conjugates have a half-life six times longer than that of free dsRNA, readily
      enter cells without the use of transfection agents, and demonstrate a high gene
      knockdown capability in a cell model.

PMID- 19170494
TI  - Metal-catalyst-free growth of single-walled carbon nanotubes.
AB  - We present a metal-catalyst-free CVD process for the high-efficiency growth of
      single-walled carbon nanotubes (SWNTs) on surface. By applying a 30-nm-thick
      SiO(2) sputtering deposited Si or Si/SiO(2) wafer as substrate and CH(4) as a
      carbon source, dense and uniform SWNT networks with high quality can be obtained
      without the presence of any metal species. Moreover, a simple patterned growth
      approach, using a scratched Si/SiO(2) wafer as substrate, is also presented for
      the growth of SWNTs with good position controllability. Our finding of the growth
      of SWNTs via a metal-catalyst-free process will provide valuable information for
      understanding the growth mechanism of SWNTs in-depth, which accordingly will
      facilitate the controllable synthesis and applications of carbon nanotubes.

PMID- 19170495
TI  - Analysis of Fusarium avenaceum metabolites produced during wet apple core rot.
AB  - Wet apple core rot (wACR) is a well-known disease of susceptible apple cultivars
      such as Gloster, Jona Gold, and Fuji. Investigations in apple orchards in
      Slovenia identified Fusarium avenaceum, a known producer of several mycotoxins,
      as the predominant causal agent of this disease. A LC-MS/MS method was developed
      for the simultaneous detection of thirteen F. avenaceum metabolites including
      moniliformin, acuminatopyrone, chrysogine, chlamydosporol, antibiotic Y, 2-amino
      14,16-dimethyloctadecan-3-ol (2-AOD-3-ol), aurofusarin, and enniatins A, A1, B,
      B1, B2, and B3 from artificially and naturally infected apples. Levels of
      moniliformin, antibiotic Y, aurofusarin, and enniatins A, A1, B, and B1 were
      quantitatively examined in artificially inoculated and naturally infected apples,
      whereas the remaining metabolites were qualitatively detected. Metabolite
      production was examined in artificially inoculated apples after 3, 7, 14, and 21
      days of incubation. Most metabolites were detected after 3 or 7 days and reached
      significantly high levels within 14 or 21 days. The highest levels of
      moniliformin, antibiotic Y, aurofusarin, and the combined sum of enniatins A, A1,
      B, and B1 were 7.3, 5.7, 152, and 12.7 microg g(-1), respectively. Seventeen of
      twenty naturally infected apples with wACR symptoms contained one or more of the
      metabolites. Fourteen of these apples contained moniliformin, antibiotic Y,
      aurofusarin, and enniatins in levels up to 2.9, 51, 167, and 3.9 microg g(-1),
      respectively. Acuminatopyrone, chrysogine, chlamydosporol, and 2-AOD-3-ol were
      detected in 4, 11, 4, and 10 apples, respectively. During wet apple core rot, F.
      avenaceum produced high amounts of mycotoxins, which may pose a risk for
      consumers of apple or processed apple products.

PMID- 19170496
TI  - High population of individualized SWCNTs through the adsorption of water-soluble
      perylenes.
AB  - The aqueous dispersion of SWCNTs in the presence of the water-soluble perylene
      derivatives 1-3 is reported. Significantly, even very low concentrations of the
      perylenes such as 0.01 wt% of the amphiphilic derivative 3, cause an efficient
      dissolution of the SWCNTs in water accompanied by a very pronounced
      individualization. The individualization of SWCNTs in water after ultrasonication
      in the presence of water-soluble aromatic perylenes was investigated in detail by
      absorption, emission, and Raman spectroscopy as well as by AFM and cryo-TEM.
      These studies also revealed that the individualization of the SWCNTs caused by
      the adsorption of 3 is much more effective than that induced by SDBS, which is
      the most frequently used surfactant for SWCNT dispersion in water. The pi-pi
      stacking interaction and the electronic interaction between the perylene unit and
      the nanotube surface is reflected, for example, by the distinct absorption and
      emission features in the UV/vis/nIR, which differ significantly from those
      observed for SWNTs dispersed in the presence of SDBS and by the quenching of the
      perylene fluorescence of 3 when being in contact with the tubes.

PMID- 19170497
TI  - Reversible lability by in situ reaction of self-assembled monolayers.
AB  - We describe a new methodology for the fabrication of controllably displaceable
      monolayers using a carboxyl-functionalized self-assembled monolayer and in situ
      Fischer esterification, a simple and reversible chemical reaction. Using an 11
      mercaptoundecanoic acid monolayer as a model system, we show that in situ
      esterification results in the creation of subtle chemical and structural defects.
      These defects promote molecular exchange reactions with n-dodecanethiol
      molecules, leading to the complete and rapid displacement of the exposed areas.
      Displacement results in well-ordered crystalline n-dodecanethiolate monolayer
      films. We also show that the complementary hydrolysis reaction can be employed to
      quench the reacted monolayer, significantly hindering further displacement. The
      generality of reversible lability was tested by applying the in situ
      esterification reaction to the structurally distinct carboxyl-functionalized
      molecule 3-mercapto-1-adamantanecarboxylic acid. Beyond its applicability to
      create mixed-composition monolayers, this methodology could be combined with
      chemical patterning techniques, such as microdisplacement printing, to fabricate
      complex functional surfaces.

PMID- 19170498
TI  - Structure-based approach to the photocontrol of protein folding.
AB  - Photoswitchable proteins offer exciting prospects for remote control of
      biochemical processes. We propose a general approach to the design of
      photoswitchable proteins based on the introduction of a photoswitchable
      intramolecular cross-linker. We chose, as a model, a FynSH3 domain for which the
      free energy of folding is less than the energy available from photoisomerization
      of the cross-linker. Taking the experimentally determined structure of the folded
      protein as a starting point, mutations were made to introduce pairs of Cys
      residues so that the distance between Cys sulfur atoms matches the ideal length
      of the cis form, but not the trans form, of the cross-linker. When the trans
      cross-linker was introduced into this L3C-L29C-T47AFynSH3 mutant, the protein was
      destabilized so that folded and unfolded forms coexisted. Irradiation of the
      cross-linker to produce the cis isomer recovered the folded, active state of the
      protein. This work shows that structure-based introduction of switchable cross
      linkers is a feasible approach for photocontrol of folding/unfolding of globular
      proteins.

PMID- 19170499
TI  - Evolution of the total synthesis of (-)-okilactomycin exploiting a tandem oxy
      cope rearrangement/oxidation, a Petasis-Ferrier union/rearrangement, and ring
      closing metathesis.
AB  - An effective, asymmetric total synthesis of the antitumor antibiotic (-)
      okilactomycin (1), as well as assignment of the absolute configuration, has been
      achieved exploiting a convergent strategy. Highlights of the synthesis include a
      diastereoselective oxy-Cope rearrangement/oxidation sequence to install the C(1)
      and C(13) stereogenic centers, a Petasis-Ferrier union/rearrangement to construct
      the highly functionalized tetrahydropyranone inscribed within the 13-membered
      macrocycle ring, employing for the first time a sterically demanding acetal, an
      intramolecular chemoselective acylation to access an embedded bicyclic lactone,
      and an efficient ring-closing metathesis (RCM) reaction to generate the
      macrocyclic ring.

PMID- 19170500
TI  - Enzymatic hydrolysis of sweet lupin, chickpea, and lentil 11S globulins decreases
      their antigenic activity.
AB  - We investigated the effects of treatments with the enzymes pepsin and trypsin on
      the in vitro immunological reactivity of the major globulins found in the seeds
      of sweet lupin, chickpea, and lentil. Polyclonal major globulin-specific
      antiserum was obtained by immunization of rabbits with a solution of the 11S
      globulin of each legume. The globulins were hydrolyzed with pepsin and trypsin
      for 1, 5, 15, and 30 min. The native globulins and their hydrolysates were
      analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      immunoblotting to identify the polypeptide bands with antigenic activity, and the
      hypoantigenicity of the hydrolysates was analyzed by enzyme-linked immunosorbent
      assay. Our results show that enzymatic treatment of the major storage protein
      (11S globulin) of sweet lupin, chickpea, and lentil with pepsin or trypsin lead
      to the formation of large amounts of short peptides and free amino acids that do
      not allow antibody binding, resulting in a weakened immunoreactivity.

PMID- 19170501
TI  - Effects of wheat albumin consumption on expression of genes related to
      lipogenesis and insulin sensitivity in adipose tissues of rats.
AB  - Suppression of postprandial hyperglycemia reduces lipogenic enzyme activities in
      the adipose tissues of normal rats. The present study investigated the expression
      of genes related to lipogenesis and insulin sensitivity in mesenteric adipose and
      epididymal adipose tissues to evaluate the effects of wheat albumin (WA) and a
      crude preparation of WA (CWA) with alpha-amylase inhibitory activity on lipid
      metabolism. Rats fed 2.5% WA, which had 12.7-fold inhibitory activity compared
      with CWA, exhibited reduced mRNA levels for G6PDH, ACO, ACS, PEPCK, and LPL in
      the mesenteric adipose, but not in the epididymal adipose tissue. Linear
      regression analyses showed that the gene expression levels of FAS, G6PDH, ACS,
      and LPL were reduced in dose-dependent manners in the mesenteric adipose tissue
      of rats fed the CWA diet. These results suggest that supplementation with CWA as
      well as WA reduces the expression of genes related to lipogenesis and insulin
      sensitivity in mesenteric adipose tissue.

PMID- 19170502
TI  - Advantage of LC-MS metabolomics methodology targeting hydrophilic compounds in
      the studies of fermented food samples.
AB  - The utility of a liquid chromatography mass spectrometry (LC-MS) method, using a
      pentafluorophenylpropyl (PFPP) bonded silica, was demonstrated in a metabolomics
      study of fermented food samples. Our LC-MS method was applied to Japanese
      fermented food (miso) of different stages of ripeness. The data acquired were
      evaluated by principal component analysis (PCA). The score plots indicated that
      the miso samples could be approximately classified into three groups, based on
      the stage of miso ripeness. The loading plots indicated that the ions responsible
      for group separation included not only amino acids and citric acid but also
      Amadori compounds. On the other hand, the miso samples were also analyzed by a
      conventional LC-MS method using an octadecyl (C(18)) column for comparison. The
      group separation of score plots from the conventional method was less clear than
      that from our method. The advantage of our LC-MS method is due to the different
      retention properties of the PFPP column and the C(18) column with hydrophilic
      compounds. Our LC-MS method will be useful for the metabolic profiling of
      fermented food samples.

PMID- 19170503
TI  - Functional polysaccharides as edible coatings for cheese.
AB  - The objective of the present study was to apply the polysaccharides from
      different nontraditional sources for cheese coatings. Chitosan, galactomannan
      from Gleditsia triacanthos, and agar from Glacilaria birdiae were tested, with
      different formulations and with the addition of plasticizer and corn oil. The
      surface properties of the cheese and the wetting capacity of the coatings on the
      cheese were determined. The three best solutions for each polysaccharide were
      chosen, further films were cast, and permeability to water vapor, oxygen, and
      carbon dioxide was determined, along with opacity. The solutions of G.
      triacanthos (formulation: 1.5% of galactomannan, 2.0% of glycerol, and 0.5% of
      oil) presented the best properties to coat the cheese: -38.76 mN x m(-1) for
      wettability; 3.24 x 10(-11) (g x (m x s x Pa)(-1)) for water vapor permeability;
      0.94 x 10(-15) and 15.35 x 10(-15) (g x m(Pa x s x m(2))(-1)) for oxygen and
      carbon dioxide permeabilities, respectively; and opacity values of 5.27%. The
      O(2) consumption and CO(2) production rates of the cheese with and without
      coating were evaluated, showing a decrease of the respiration rates when the
      coating was applied. The uncoated cheese had an extensive mold growth at the
      surface when compared with the coated cheese. The results show that these
      coatings can be applied as an alternative to synthetic coatings.

PMID- 19170504
TI  - A series of kokumi peptides impart the long-lasting mouthfulness of matured Gouda
      cheese.
AB  - Comparative sensory analysis revealed that a 44-week-matured Gouda cheese (GC44)
      exhibited a much more pronounced mouthfulness and long-lasting taste complexity
      when compared to a young Gouda cheese ripened for only 4 weeks (GC4). To identify
      the molecules underlying that so-called kokumi sensation, a sensomics approach
      was applied on the water-soluble extract (WSE44) of GC44 by combining gel
      permeation chromatography (GPC) with analytical sensory tools. HPLC-MS/MS
      experiments on GPC fractions inducing a kokumi sensation when tasted in an
      aqueous biomimetic taste recombinant solution (rWSE44) enabled the identification
      of 8 alpha-L-glutamyl and 10 gamma-L-glutamyl dipeptides as candidate kokumi
      enhancing molecules. Among those, only the gamma-L-glutamyl dipeptides were found
      to impart an enhanced kokumi sensation to the matured cheese, whereas none of the
      alpha-glutamyl peptides were found to be active. Among the gamma-L-glutamyl
      peptides, the candidates gamma-Glu-Glu, gamma-Glu-Gly, gamma-Glu-Gln, gamma-Glu
      Met, gamma-Glu-Leu, and gamma-Glu-His, present in GC44 in concentrations between
      4.11 and 17.66 micromol/kg, were identified for the first time as the key kokumi
      molecules enhancing mouthfulness and complex taste continuity of the matured
      cheese.

PMID- 19170505
TI  - Determination and applications of the molar absorptivity of phenolic adducts with
      captopril and mesna.
AB  - Captopril and mesna are molecules with a free thiol group, used as active
      ingredients due to their hypotensor and mucolytic properties, respectively. These
      compounds cross the hematoencephalic barrier and, due to the reactivity of their
      thiol group, can form adducts with the o-quinones formed during the oxidation of
      mono- and o-diphenols. Polyphenol oxidase from plants and fungi can be used as a
      tool for generating o-quinones in their action on o-diphenols and facilitate the
      formation of adducts in the presence of captopril or mesna. The
      spectrophotometric characterization of these adducts is useful from several
      points of view. Here, using the end-point method, which involves the exhaustion
      of oxygen in the medium, we determined the molar absorptivity of the adducts of
      different o-diphenols with captopril and mesna. Besides the analytical interest
      of this approach, we also use it to make a kinetic characterization of polyphenol
      oxidase as it acts on o-diphenolic substrates that produce unstable o-quinones.

PMID- 19170507
TI  - Intracrystalline oxidation of thiosulfate-intercalated layered double hydroxides.
AB  - Thiosulfate-intercalated zinc-aluminum LDH was prepared by anion exchange
      reaction. The interlayer thiosulfate ions of this LDH could be quantitatively
      oxidized to tetrathionate ions using iodine and sulfate ions using H2O2. Both of
      these intracrystalline reactions are topotactic in nature. The reaction of the
      LDH with molecular iodine makes it a potential material for the removal of
      radioactive iodine from effluents.

PMID- 19170508
TI  - Sensitization and elicitation of an allergic reaction to wheat gliadins in mice.
AB  - We developed a mouse model of allergy to wheat flour gliadins, a protein fraction
      containing major wheat allergens. We compared the antibody responses (i.e.,
      specific IgE and IgG1) and the profiles of cytokines secreted by reactivated
      splenocytes induced after intraperitoneal injections of gliadins in three strains
      of mice, namely, Balb/cJ, B10.A, and C3H/HeJ. The intensities of the allergic
      reactions elicited by intranasal challenge were also compared. Both the
      sensitization and elicitation were the highest in Balb/cJ mice, whereas weak or
      no reaction was observed in the others strains. Interestingly, the specificity of
      the mouse IgE against the different gliadins (i.e., alpha-, beta-, gamma-, omega
      1,2-, and omega 5-gliadin) was similar to that observed in children allergic to
      wheat flour. Balb/cJ mice may thus provide a relevant model for the study of
      sensitization and elicitation by wheat gliadins and for improving our
      understanding of the specific role and mechanisms of action of the different
      classes of gliadins.

PMID- 19170510
TI  - Nanoprecipitation of polymethylmethacrylate by solvent shifting: 1. Boundaries.
AB  - Nanoparticles of polymethylmethacrylate (PMMA) have been produced through the
      solvent shifting process (also called the "Ouzo process") in which water
      (nonsolvent) was added to a solution of PMMA in acetone or tetrahydrofuran
      (solvent). At low concentrations of PMMA in the initial solution, and for large
      additions of water, the process yielded PMMA nanoparticles with a narrow
      distribution of particle sizes. The mean particle diameter varied as a power law
      of the initial PMMA concentration in the solvent, in agreement with the
      predictions from the Smoluchowski equation for an aggregation process that has
      definite "start" and "stop" times. At higher PMMA concentrations, the mixing
      process yielded microparticles coexisting with PMMA nanoparticles. The boundary
      that separates the Ouzo region of compositions (PMMA nanoparticles only), from
      the "non-Ouzo" region (nano- and microparticles) has been determined. This
      boundary does not appear to have any relation to the spinodal decomposition line
      of the ternary solutions: the transition from Ouzo to non-Ouzo behavior must have
      another unknown origin.

PMID- 19170509
TI  - Male-produced aggregation pheromone blend in Platypus koryoensis.
AB  - The ambrosia beetle, Platypus koryoensis , is a vector of Korean oak wilt
      disease, which causes massive mortality of oak trees (mainly Quercus mongolica )
      in Korea. So that a semiochemical-based control method could be developed, its
      aggregation pheromone was investigated. Whole body extract and body part extracts
      of male and female P. koryoensis were analysized using gas chromatography-flame
      ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS).
      All samples of male extracts contained nerol, neral, geraniol, and geranial.
      Those compounds were detected from female whole body extract as minor
      constituents and not detected from any female body part extracts. In addition to
      those compounds, citronellol was detected from the extract of boring dust
      produced by an unmated male. However, none of the five compounds were detected
      from the extract of boring dust produced by mated males and females or in
      artificial sawdust obtained from a beetle-infected Q. mongolica log. Male and
      female antennae of P. koryoensis responded to all five compounds in an
      electroantennography test. The blend of five components was tested in the field
      and attractive for male and female P. koryoensis. This result suggested that the
      blend of citronellol, nerol, neral, geraniol, and geranial served as an
      aggregation pheromone to P. koryoensis.

PMID- 19170511
TI  - Preparation of achiral and chiral (E)-enaminopyran-2,4-diones and their
      phytotoxic activity.
AB  - A short and efficient approach to a range of new chiral and achiral
      functionalized (E)-enaminopyran-2,4-diones starting with commercially available
      dehydroacetic acid is described. The phytotoxic properties of these (E)
      enaminopyran-2,4-diones were evaluated by their ability to interfere with the
      growth of Sorghum bicolor and Cucumis sativus seedlings. A different sensitivity
      of the two crops was evident with the (E)-enaminopyran-2,4-diones. The most
      active compounds were also tested against two weeds, Ipomoea grandifolia and
      Brachiaria decumbens. To the best of our knowledge, this is the first report
      describing enaminopyran-2,4-diones as potential plant growth regulators.

PMID- 19170513
TI  - Development of a robust and repeatable UPLC-MS method for the long-term
      metabolomic study of human serum.
AB  - A method for performing untargeted metabolomic analysis of human serum has been
      developed based on protein precipitation followed by Ultra Performance Liquid
      Chromatography and Time-of-Flight mass spectrometry (UPLC-TOF-MS). This method
      was specifically designed to fulfill the requirements of a long-term metabolomic
      study, spanning more than 3 years, and it was subsequently thoroughly evaluated
      for robustness and repeatability. We describe here the observed drift in
      instrumental performance over time and its improvement with adjustment of the
      length of analytical block. The optimal setup for our purpose was further
      validated against a set of serum samples from 30 healthy individuals. We also
      assessed the reproducibility of chromatographic columns with the same chemistry
      of stationary phase from the same manufacturer but from different production
      batches. The results have allowed the authors to prepare SOPs for "fit for
      purpose" long-term UPLC-MS metabolomic studies, such as are being employed in the
      HUSERMET project. This method allows the acquisition of data and subsequent
      comparison of data collected across many months or years.

PMID- 19170514
TI  - Application of physicochemically modified silicon substrates as reverse-phase
      protein microarrays.
AB  - Physicochemically modified silicon substrates can provide a high quality
      alternative to nitrocellulose-coated glass slides for use in reverse-phase
      protein microarrays. Enhancement of protein microarray sensitivities is an
      important goal, especially because molecular targets within patient tissues exist
      in low abundance. The ideal array substrate has a high protein binding affinity
      and low intrinsic background signal. Silicon, which has low intrinsic
      autofluorescence, is being explored as a potential microarray surface. In a
      previous paper ( Nijdam , A. J. ; Cheng , M. M.-C. ; Fedele , R. ; Geho , D. H. ;
      Herrmann , P. ; Killian , K. ; Espina , V. ; Petricoin , E. F. ; Liotta , L. A. ;
      Ferrari , M. Physicochemically Modified Silicon as Substrate for Protein
      Microarrays . Biomaterials 2007 , 28 , 550 - 558 ), it is shown that
      physicochemical modification of silicon substrates increases the binding of
      protein to silicon to a level comparable with that of nitrocellulose. Here, we
      apply such substrates in a reverse-phase protein microarray setting in two model
      systems.

PMID- 19170515
TI  - Structures and aggregation of the methylamine-borane molecules, Me(n)H(3
      n)N.BH(3) (n = 1-3), studied by X-ray diffraction, gas-phase electron
      diffraction, and quantum chemical calculations.
AB  - The structures of the molecules methylamine-borane, MeH(2)N.BH(3), and
      dimethylamine-borane, Me(2)HN.BH(3), have been investigated by gas-phase electron
      diffraction (GED) and quantum chemical calculations. The crystal structures have
      also been determined for methylamine-, dimethylamine-, and trimethylamine-borane,
      Me(n)H(3-n)N.BH(3) (n = 1-3); these are noteworthy for what they reveal about the
      intermolecular interactions and, particularly, the N-H...H-B dihydrogen bonding
      in the cases where n = 1 or 2. Hence, structures are now known for all the
      members of the ammonia- and amine-borane series Me(n)H(3-n)N.BH(3) (n = 0-3) in
      both the gas and solid phases. The structural variations and energetics of
      formation of the gaseous adducts are discussed in relation to the basicity of the
      Me(n)H(3-n)N fragment. The relative importance of secondary interactions in the
      solid adducts with n = 0-3 has been assessed by the semi-classical density sums
      (SCDS-PIXEL) approach.

PMID- 19170516
TI  - Detection of glucose based on direct electron transfer reaction of glucose
      oxidase immobilized on highly ordered polyaniline nanotubes.
AB  - An amperometric glucose biosensor based on the direct electron transfer of
      glucose oxidase (GOx) was developed by electrochemically entrapping GOx onto the
      inner wall of highly ordered polyaniline nanotubes (nanoPANi), which was
      synthesized using anodic aluminum oxide (AAO) membrane as a template. The cyclic
      voltammetric results indicated that GOx immobilized on the nanoPANi underwent
      direct electron transfer reaction, and the cyclic voltammogram displayed a pair
      of well-defined and nearly symmetric redox peaks with a formal potential of -405
      +/- 5 mV and an apparent electron transfer rate constant of 5.8 +/- 1.6 s(-1).
      The biosensor had good electrocatalytic activity toward oxidation of glucose and
      exhibited a rapid response (approximately 3 s), a low detection limit (0.3 +/-
      0.1 microM), a useful linear range (0.01-5.5 mM), high sensitivity (97.18 +/-
      4.62 microA mM(-1) cm(-2)), higher biological affinity (the apparent Michaelis
      Mentan constant was estimated to be 2.37 +/- 0.5 mM) as well as good stability
      and repeatability. In addition, the common interfering species, such as ascorbic
      acid, uric acid, and 4-acetamidophenol, did not cause any interference due to the
      use of a low detection potential (-0.3 V vs SCE). The biosensor can also be used
      for quantification of the concentration of glucose in real clinical samples.

PMID- 19170517
TI  - Use of Raman microscopy and multivariate data analysis to observe the biomimetic
      growth of carbonated hydroxyapatite on bioactive glass.
AB  - In the present contribution, the biomimetic growth of carbonated hydroxyapatite
      (HA) on bioactive glass were investigated by Raman microscopy. Bioactive glass
      samples were immersed in simulated body fluid (SBF) buffered solution at pH 7.40
      up to 17 days at 37 degrees C. Raman microscopy mapping was performed on the
      bioglass samples immersed in SBF solution for different periods of time. The
      collected data was then analyzed using the band-target entropy minimization
      technique to extract the observable pure component Raman spectral information. In
      this study, the pure component Raman spectra of the precursor amorphous calcium
      phosphate, transient octacalcium phosphate, and matured HA were all recovered. In
      addition, pure component Raman spectra of calcite, silica glass, and some organic
      impurities were also recovered. The resolved pure component spectra were fit to
      the normalized measured Raman data to provide the spatial distribution of these
      species on the sample surfaces. The current results show that Raman microscopy
      and multivariate data analysis provide a sensitive and accurate tool to
      characterize the surface morphology, as well as to give more specific information
      on the chemical species present and the phase transformation of phosphate species
      during the formation of HA on bioactive glass.

PMID- 19170518
TI  - Ligand-specific conformation determines agonist activation and antagonist
      blockade in purified human thromboxane A2 receptor.
AB  - The binding of an agonist to a G protein-coupled receptor (GPCR) causes its
      coupling to different G proteins, which mediate signaling. However, the binding
      of an antagonist to the same site of the GPCR could not induce coupling. To
      understand the molecular mechanism involved, the structural flexibility of the
      purified human thromboxane A2 receptor (TP) was characterized by spectroscopic
      approaches, while bound to an agonist or antagonist. Circular dichroism not only
      revealed that the purified TP adopted more than 50% helical conformation in
      solution but also showed that the antagonist, SQ29,548, could induce more of a
      beta-sheet structure in the TP than that of the agonist, U46619. Also,
      fluorescence studies showed that the antagonist induced the intrinsic Trp
      fluorescence signal change more than the agonist. Furthermore, three of the nine
      tryptophan residues involved in the different ligand-based structural changes
      were demonstrated by NMR spectroscopy. Low pH-induced changes in the receptor
      conformation and molecular interaction field dramatically increased the agonist
      binding but did not significantly affect the antagonist binding. Different
      conformational changes were also observed in the TP reconstituted into
      phosphatidylcholine/phosphatidylserine/phosphatydylethanolamine-formed liposomes.
      These studies are the first to show a possible mechanism of the ligand-specific
      conformation-dependent agonist activation and antagonist blockage in the GPCR.

PMID- 19170519
TI  - Potent and selective inhibitors of breast cancer resistance protein (ABCG2)
      derived from the p-glycoprotein (ABCB1) modulator tariquidar.
AB  - The efflux pumps ABCB1 (p-gp, MDR1) and ABCG2 (BCRP) are expressed to a high
      extent by endothelial cells at the blood-brain barrier (BBB) and other barrier
      tissues and are involved in drug resistance of tumor (stem) cells. Whereas
      numerous ABCB1 inhibitors are known, only a few ABCG2 modulators with
      submicromolar activity have been published. Starting from tariquidar (4)
      analogues as ABCB1 modulators, minimal structural modifications resulted in a
      drastic shift in favor of ABCG2 inhibition. Highest potency was found when the
      3,4-dimethoxy-2-(quinoline-3-carbonylamino)benzoyl moiety in 4 was replaced with
      a 4-methoxycarbonylbenzoyl moiety bearing a hetarylcarboxamido group in 3
      position, e.g., quinoline-3-carboxamido (5, IC(50): 119 nM) or quinoline-2
      carboxamido (6, IC(50): 60 nM, flow cytometric mitoxantrone efflux assay,
      topotecan-resistant MCF-7 breast cancer cells); the selectivity for ABCG2 over
      ABCB1 was about 100-500 fold and the compounds were inactive at ABCC2 (MRP2).
      Chemosensitivity assays against MCF-7/Topo cells revealed that the nontoxic
      inhibitor 6 completely reverted ABCG2-mediated topotecan resistance at
      concentrations >100 nM, whereas 5 showed ABCG2 independent cytotoxicity. ABCG2
      inhibitors might be useful for cancer treatment with respect to reversal of
      multidrug resistance, overcoming the BBB and targeting of tumor stem cells.

PMID- 19170520
TI  - Modulation of pK(a) of Brooker's merocyanine by DNA hybridization.
AB  - Brooker's merocyanine (BM), which changes its emission and absorption maxima upon
      protonation, was introduced into oligodeoxyribonucleotide (ODN) via d-threoninol
      by postsynthetic modification on a CPG (controlled-pore glass) support. The pK(a)
      of BM in the modified ODN increased from 9.5 to 10.1 upon hybridization. As a
      result, absorption maxima shifted from 492 to 432 nm at pH 10.0 by the presence
      of its complementary strand. This spectral shift was sufficiently large so that
      DNA hybridization could easily be discriminated even by the naked eye; the color
      of the solution changed from orange to yellow upon hybridization. In addition,
      the fluorescence emission was strongly quenched upon hybridization, demonstrating
      that this probe can also detect the target DNA by the fluorescence change.
      Ratiometric detection of hybridization was also possible by simultaneous
      excitation of both protonated and deprotonated BMs. Furthermore, we could also
      modulate its pK(a) by the antiparallel stacking of two BM molecules in the
      duplex; the pK(a) of BM decreased from 10.1 to 9.7 by the stacking of two BMs in
      an antiparallel manner. Thus, control of the microenvironment around the BM
      molecule allowed modulation of its pK(a), which is applicable to the sequence
      specific recognition of target DNA.

PMID- 19170521
TI  - Specific targeting of highly conserved residues in the HIV-1 reverse
      transcriptase primer grip region. 2. Stereoselective interaction to overcome the
      effects of drug resistant mutations.
AB  - Starting from the prototypic compound 4, we describe new, potent, and broad
      spectrum pyrrolobenzo(pyrido)oxazepinones antivirals. A biochemical and
      enzymological investigation was performed for defining their mechanism of
      inhibition at either recombinant HIV-1 RT wild type and non-nucleoside reverse
      transcriptase inhibitors (NNRTIs)-resistant mutants. For the novel compounds (S)
      (+)-5 and (S)-(-)-7, a clear-cut stereoselective mechanism of enzyme inhibition
      was found. Molecular modeling studies were performed for revealing the
      underpinnings of this behavior.

PMID- 19170522
TI  - Structural effects in molecular metal halides.
AB  - Metal halides are a relatively large class of inorganic compounds that
      participate in many industrial processes, from halogen metallurgy to the
      production of semiconductors. Because most metal halides are ionic crystals at
      ambient conditions, the term "molecular metal halides" usually refers to vapor
      phase species. These gas-phase molecules have a special place in basic research
      because they exhibit the widest range of chemical bonding from the purely ionic
      to mostly covalent bonding through to weakly interacting systems. Although our
      focus is basic research, knowledge of the structural and thermodynamic properties
      of gas-phase metal halides is also important in industrial processes. In this
      Account, we review our most recent work on metal halide molecular structures. Our
      studies are based on electron diffraction and vibrational spectroscopy, and
      increasingly, we have augmented our experimental work with quantum chemical
      computations. Using both experimental and computational techniques has enabled us
      to determine intriguing structural effects with better accuracy than using either
      technique alone. We loosely group our discussion based on structural effects
      including "floppiness", relativistic effects, vibronic interactions, and finally,
      undiscovered molecules with computational thermodynamic stability. Floppiness, or
      serious "nonrigidity", is a typical characteristic of metal halides and makes
      their study challenging for both experimentalists and theoreticians. Relativistic
      effects are mostly responsible for the unique structure of gold and mercury
      halides. These molecules have shorter-than-expected bonds and often have unusual
      geometrical configurations. The gold monohalide and mercury dihalide dimers and
      the molecular-type crystal structure of HgCl(2) are examples. We also examined
      spin-orbit coupling and the possible effect of the 4f electrons on the structure
      of lanthanide trihalides. Unexpectedly, we found that the geometry of their
      dimers depends on the f electron configuration. Metal halides are unique in
      exhibiting strong vibronic interactions such as the Jahn-Teller effect and the
      related Renner-Teller effect. Some metal trihalide molecules have an almost T
      shape due to static Jahn-Teller distortions. The nonlinear structure with a 150
      degree bond angle of the chromium dichloride molecule demonstrates the Renner
      Teller effect. Finally, we present a few examples of unknown structures that
      appear to be thermodynamically stable, including gold and silver triiodides and
      all silver subhalides. The combination of experimental and computational
      techniques has brought new insights to the structural chemistry of metal halides.
      We expect that the continuing progress in computational chemistry will shed
      further light on the intricate details of these and other molecular structures.

PMID- 19170523
TI  - Surface molecular imprinting on Mn-doped ZnS quantum dots for room-temperature
      phosphorescence optosensing of pentachlorophenol in water.
AB  - A new type of molecularly imprinted polymer (MIP)-based room-temperature
      phosphorescence (RTP) optosensor was developed by anchoring the MIP layer on the
      surface of Mn-doped ZnS quantum dots (QDs) via a surface molecular imprinting
      process. The synergetic combination of the RTP property of the Mn-doped ZnS QDs
      and the merits of the surface imprinting polymers not only improves the RTP
      selectivity of the Mn-doped ZnS QDs but also makes the MIP-based RTP optosensor
      also applicable to selective detecting of those nonphosphorescent analytes
      without the need for any inducers and derivatization. The new MIP-based RTP
      sensing protocol was applied to detect trace pentachlorophenol (PCP) in water
      samples without the interference of autofluorescence and scattering light of
      matrixes. The detection limit for PCP was 86 nM, and the precision for five
      replicate detections of 0.4 microM PCP was 2.8% (relative standard deviation).
      The recovery of spiked PCP in river water samples ranged from 93% to 106%.

PMID- 19170525
TI  - Electrochemical determination of thioredoxin redox states.
AB  - Thioredoxin (TRX) is a general protein disulfide reductase with a large number of
      biological functions, including its roles in human diseases. The TRX redox
      mechanism is based on reversible oxidation of two cysteine thiol groups to a
      disulfide, accompanied by the transfer of two protons. Using constant-current
      chronopotentiometric stripping analysis (CPSA) and the electrocatalytic TRX peak
      H, we have determined redox states of TRX at submicromolar TRX concentrations. A
      concentration of 1 nM TRX produces a well-developed peak H at moderate
      accumulation time without stirring. On the basis of this peak, interactions of 4
      hydroxy-2-nonenal (HNE, product of lipid peroxidation) with TRX and the formation
      of TRX-HNE adducts were studied. CPSA of TRX at a carbon electrode is less
      sensitive and does not discriminate between reduced and oxidized forms of TRX.

PMID- 19170524
TI  - Third-generation immucillins: syntheses and bioactivities of acyclic immucillin
      inhibitors of human purine nucleoside phosphorylase.
AB  - ImmH (1) and DADMe-ImmH (2) are potent inhibitors of human purine nucleoside
      phoshorylase (PNP), developed by us and currently in clinical trials for the
      treatment of a variety of T-cell related diseases. Compounds 1 and 2 were used as
      templates for the design and synthesis of a series of acyclic immucillin
      analogues (8-38) in order to identify simplified alternatives to 1 and 2. SerMe
      ImmG (8) and DATMe-ImmG (9) displayed the lowest inhibition constants of 2.1 and
      3.4 pM, respectively, vs PNP. It was postulated that the flexible natures of 8
      and 9 enabled them to adopt conformations resembling those of 1 and 2 within the
      active site of PNP and that the positioning of two hydroxyl groups was critical
      for picomolar activity. SerMe-ImmH (10, K(d) = 5.2 pM) was shown to be orally
      available in mice with a long biological residence time on blood PNP.

PMID- 19170526
TI  - Quasi-equilibrium AFM measurement of disjoining pressure in lubricant nanofilms
      II: Effect of substrate materials.
AB  - Atomic force microscopy (AFM) was used to measure the disjoining pressures of
      perfluoropolyether lubricant films (0.8-4.3 nm of Fomblin Z03) on both silicon
      wafers and hard drive disks coated with a diamondlike carbon overcoat.
      Differences in the disjoining pressure between the two systems were expected to
      be due to variations in the strength of van der Waals interactions. Lifshitz
      theory calculations suggest that this substrate switch will lead to relatively
      small changes in disjoining pressure as compared to the more pronounced effects
      reported due to changes in lubricant chemistry. We demonstrate the sensitivity of
      our AFM method by distinguishing between these similar systems.

PMID- 19170527
TI  - Real-time monitoring of the activity and kinetics of T4 polynucleotide kinase by
      a singly labeled DNA-hairpin smart probe coupled with lambda exonuclease
      cleavage.
AB  - We describe a novel method for real-time monitoring of the activity and kinetics
      of T4 polynucleotide kinase (PNK) by use of a singly fluorophore-labeled DNA
      hairpin smart probe (SP) coupled with lambda exonuclease (lambda exo) cleavage.
      The method was performed in a sealed reaction tube and offered more sensitive,
      fast, high-throughput, and cost-effective detection. The SP was designed with a
      fluorophore at the 3'-end, and the fluorescence was quenched by a GGG-triplet at
      the 5'-end without any other additional quenchers. The 5'-hydroxyl group of the
      SP was phosphorylated by T4 PNK in the presence of ATP, and the resulting 5'
      phosphoryl end product was promptly cleaved by lambda exo, which caused
      significant enhancement of fluorescence. A fast and accurate method for assaying
      the kinase activity of T4 PNK was developed with a wide linear detection range
      from 0.022 to 5.6 nM s(-1). The phosphorylation reaction was monitored at varying
      substrate concentrations at the molecular level, and K(m), V(max), and K(cat)
      values were all calculated. Furthermore, the effects of ATP concentration and
      salts were investigated. The developed method can be easily adapted to the
      detection of many other nucleic acid enzymes and may find widespread
      applications.

PMID- 19170528
TI  - Double-tagging polymerase chain reaction with a thiolated primer and
      electrochemical genosensing based on gold nanocomposite sensor for food safety.
AB  - A novel material for electrochemical biosensing based on rigid conducting gold
      nanocomposite (nano-AuGEC) is presented. Islands of chemisorbing material (gold
      nanoparticles) surrounded by nonreactive, rigid, and conducting graphite epoxy
      composite are thus achieved to avoid the stringent control of surface coverage
      parameters required during immobilization of thiolated oligos in continuous gold
      surfaces. The spatial resolution of the immobilized thiolated DNA was easily
      controlled by merely varying the percentage of gold nanoparticles in the
      composition of the composite. As low as 9 fmol (60 pM) of synthetic DNA were
      detected in hybridization experiments when using a thiolated probe. Moreover, for
      the first time a double tagging PCR strategy was performed with a thiolated
      primer for the detection of Salmonella sp., one of the most important foodborne
      pathogens affecting food safety. This assay was performed by double-labeling the
      amplicon during the PCR with a -DIG and -SH set of labeled primers. The thiolated
      end allows the immobilization of the amplicon on the nano-AuGEC electrode, while
      digoxigenin allows the electrochemical detection with the antiDIG-HRP reporter in
      the femtomole range. Rigid conducting gold nanocomposite represents a good
      material for the improved and oriented immobilization of biomolecules with
      excellent transducing properties for the construction of a wide range of
      electrochemical biosensors such as immunosensors, genosensors, and enzymosensors.

PMID- 19170529
TI  - Sensitive and colorimetric detection of the structural evolution of superoxide
      dismutase with gold nanoparticles.
AB  - The detection and characterization of protein aggregates are critical in terms of
      advanced diagnostic applications and investigations of protein stability. A
      variety of analytical methods (e.g., circular dichroism, size exclusion
      chromatography, and fluorescence microscopy) have been used in this regard, but
      they are limited in the trace detection of the structural evolution of protein
      aggregation. Here we report the gold nanoparticle (AuNP)-based highly sensitive
      and colorimetric detection of the temporal evolution of superoxide dismutase
      (SOD1) aggregates implicated in the pathology of amyotrophic lateral sclerosis
      (ALS). For the temporal discrimination of SOD1 aggregation, AuNPs were conjugated
      with SOD1 monomers (SOD1-AuNPs). Upon exposure of the probes (SOD1-AuNPs) with
      SOD1 aggregates, significant changes in both surface plasmon resonance spectra
      and concomitant colors were observed which are attributed to the formation of
      probe aggregates of variable sizes onto the SOD1 aggregates.

PMID- 19170530
TI  - Thioamide hydroxypyrothiones supersede amide hydroxypyrothiones in potency
      against anthrax lethal factor.
AB  - Anthrax lethal factor (LF) is a critical virulence factor in the pathogenesis of
      anthrax. A structure-activity relationship (SAR) of potential lethal factor
      inhibitors (LFi) is presented in which the zinc-binding group (ZBG), linker, and
      backbone moieties for a series of hydroxypyrone-based compounds were
      systematically varied. It was found that hydroxypyrothione ZBGs generate more
      potent inhibitors than hydroxypyrone ZBGs. Furthermore, coupling the
      hydroxypyrothione to a backbone group via a thioamide bond improves potency when
      compared to an amide linker. QM/MM studies show that the thioamide bond in these
      inhibitors allows for the formation of two additional hydrogen bonds with the
      protein active site. In both types of hydroxypyrothione compounds, ligand
      efficiencies of 0.29-0.54 kcal mol(-1) per heavy atom were achieved. The results
      highlight the need for a better understanding to optimize the interplay between
      the ZBG, linker, and backbone to get improved LFi.

PMID- 19170532
TI  - Efficient synthesis of gamma-keto esters through neighboring carbonyl group
      assisted regioselective hydration of 3-alkynoates.
AB  - The Au(III)-catalyzed hydration of 3-alkynoates led to a practical one-step
      synthesis of gamma-keto esters in high yields, through a carbonyl group
      participation enabled by a favored 5-endodig cyclization. This mild-aqueous
      ethanol, room temperature, and atom-economical method has been used effectively
      with a wide range of substrates. Using the same conditions, a 2-alkynoate
      produced the corresponding beta-keto ester in high yield.

PMID- 19170533
TI  - Diastereoselective synthesis of bicyclic gamma-lactams via ring expansion of
      monocyclic beta-lactams.
AB  - cis-4-(1-Chloro-1-methylethyl)-1-(omega-hydroxyalkyl)azetidin-2-ones were
      diastereoselectively transformed into novel trans-1-aza-4-oxabicyclo[3.3.0]octan
      8-ones and trans-1-aza-5-oxabicyclo[4.3.0]nonan-9-ones upon treatment with 1
      equiv of AgBF4 and pyridine in toluene via intramolecular nucleophilic trapping
      of N-acyliminium intermediates by the hydroxyl moiety. Additionally, the
      corresponding aza-analogues of the aforementioned bicyclic gamma-lactams (i.e.,
      trans-1,4-diazabicyclo[3.3.0]octan-8-ones and trans-1,5-diazabicyclo[4.3.0]nonan
      9-ones) were prepared in a convenient way starting from cis-4-(1-chloro-1
      methylethyl)-1-{omega-[(tert-butoxycarbonyl)amino]alkyl}azetidin-2-ones applying
      the same reaction conditions. The intermediate N-acyliminium ions were formed by
      ring expansion of the starting beta-lactams through generation of a transient
      silver(I)-induced carbenium ion.

PMID- 19170534
TI  - An unexpected N-heterocyclic carbene-catalyzed annulation of enals and nitroso
      compounds.
AB  - The N-heterocyclic carbene (NHC)-catalyzed annulation of enals with nitroso
      compounds in the presence of DBU in THF has been described. Unexpected seven
      membered 4-azalactones were formed according to a process involving a 1,2
      Bamberger-type rearrangement.

PMID- 19170535
TI  - Application of HPLC and MALDI-TOF MS for studying as-synthesized ligand-protected
      gold nanoclusters products.
AB  - Samples of polydisperse gold nanoclusters (AuNCs) protected with monolayers of N
      acetyl-L-cysteine (NAC) have been chromatographically separated by a C18 column
      (4.6 mm x 250 mm) using a gradient elution program with a mobile phase of
      methanol (MeOH)/water containing tetrabutylammonium fluoride (Bu(4)N(+)F(-)) and
      sodium chloride. The effects of Bu(4)N(+)F(-) and MeOH on the separation have
      been investigated in detail. In conjunction with absorbance-based, fluorescence,
      and electrochemical detectors, the elution order of these water-soluble AuNCs is
      confirmed according to their core size in an ascending order. The onset oxidation
      potential closely follows the core size of AuNC. The separated fractions from
      high-performance liquid chromatography (HPLC) were collected and analyzed by
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry to
      determine the number of Au atoms in the fractions. The sizes of AuNCs in some
      selected HPLC fractions were also assessed by transmission electron microscopy
      and high-resolution transmission electron microscopy. Photoluminescence spectra
      of the fractions show that the luminescent shift in the visible/near-infrared
      region does not follow with the core size of AuNC. More importantly, the proposed
      HPLC methodology has been successfully applied to analyze various polydisperse
      AuNC products synthesized from different gold-to-ligand mole ratios (Au/NAC) and
      reaction temperatures. The results confirm that larger Au/NAC and higher
      temperature will produce larger core size AuNCs products with narrower
      dispersity. In addition, AuNC samples obtained from various synthesis reaction
      times were analyzed by our HPLC methodology, demonstrating that the reaction's
      behavior follows the nucleation-growth-disintegration process.

PMID- 19170536
TI  - Structure of the analgesic mu-conotoxin KIIIA and effects on the structure and
      function of disulfide deletion.
AB  - Mu-conotoxin mu-KIIIA, from Conus kinoshitai, blocks mammalian neuronal voltage
      gated sodium channels (VGSCs) and is a potent analgesic following systemic
      administration in mice. We have determined its solution structure using NMR
      spectroscopy. Key residues identified previously as being important for activity
      against VGSCs (Lys7, Trp8, Arg10, Asp11, His12, and Arg14) all reside on an alpha
      helix with the exception of Arg14. To further probe structure-activity
      relationships of this toxin against VGSC subtypes, we have characterized the
      analogue mu-KIIIA[C1A,C9A], in which the Cys residues involved in one of the
      three disulfides in mu-KIIIA were replaced with Ala. Its structure is quite
      similar to that of mu-KIIIA, indicating that the Cys1-Cys9 disulfide bond could
      be removed without any significant distortion of the alpha-helix bearing the key
      residues. Consistent with this, mu-KIIIA[C1A,C9A] retained activity against
      VGSCs, with its rank order of potency being essentially the same as that of mu
      KIIIA, namely, Na(V)1.2 > Na(V)1.4 > Na(V)1.7 >or= Na(V)1.1 > Na(V)1.3 >
      Na(V)1.5. Kinetics of block were obtained for Na(V)1.2, Na(V)1.4, and Na(V)1.7,
      and in each case, both k(on) and k(off) values of mu-KIIIA[C1A,C9A] were larger
      than those of mu-KIIIA. Our results show that the key residues for VGSC binding
      lie mostly on an alpha-helix and that the first disulfide bond can be removed
      without significantly affecting the structure of this helix, although the
      modification accelerates the on and off rates of the peptide against all tested
      VGSC subtypes. These findings lay the groundwork for the design of minimized
      peptides and helical mimetics as novel analgesics.

PMID- 19170538
TI  - A convenient synthesis of (S)-H4-BINOL and its derivatives via hydrogenation of
      monoesters of BINOL.
AB  - A new multigram synthesis of chiral (S)-H(4)-BINOL and its derivatives in
      moderate to high yield (up to 83% total yield) via monoesterification of (S)
      BINOL, hydrogenation, and saponification reaction was described. The two new
      monomethylated (S)-H(4)-BINOL obtained may be useful materials in asymmetric
      catalysis.

PMID- 19170537
TI  - Structure of the N terminus of a nonmuscle alpha-tropomyosin in complex with the
      C terminus: implications for actin binding.
AB  - Tropomyosin is a coiled-coil actin binding protein that stabilizes the filament,
      protects it from severing, and cooperatively regulates actin's interaction with
      myosin. Depending on the first coding exon, tropomyosins are low molecular weight
      (LMW), found in the cytoskeleton and predominant in transformed cells, or high
      molecular weight (HMW), found in muscle and nonmuscle cells. The N- and C
      terminal ends form a complex that allows tropomyosin to associate N terminus-to-C
      terminus along the actin filament. We determined the structure of a LMW
      tropomyosin N-terminal model peptide complexed with a smooth/nonmuscle
      tropomyosin C-terminal peptide. Using NMR and circular dichroism we showed that
      both ends become more helical upon complex formation but that the C-terminal
      peptide is partially unfolded at 20 degrees C. The first five residues of the N
      terminus that are disordered in the free peptide are more helical and are part of
      the overlap complex. NMR data indicate residues 2-17 bind to the C terminus in
      the complex. The data support a model for the LMW overlap complex that is
      homologous to the striated muscle tropomyosin complex in which the ends are
      oriented in parallel N terminus-to-C terminus with the plane of the N-terminal
      coiled coil perpendicular to the plane of the C terminus. The main difference is
      that the overlap spans 16 residues in the LMW tropomyosin complex compared to 11
      residues in the HMW striated muscle overlap complex. We discuss the relevance of
      a stable but dynamic intermolecular junction for high-affinity binding to actin.

PMID- 19170539
TI  - Total synthesis of (+/-)-rhazinal using novel palladium-catalyzed cyclizations.
AB  - A concise synthesis of (+/-)-rhazinal that hinges on novel oxidative Heck
      cyclizations and palladium-catalyzed direct couplings is described. An X-ray
      structure of N-MOM-rhazinal, which provides insight into the conformation of the
      strained 9-membered lactam ring, is described.

PMID- 19170540
TI  - An efficient carbene-catalyzed access to 3,4-dihydrocoumarins.
AB  - Dihydrocoumarins play an important role as flavor and fragrance compounds and can
      be prepared efficiently from o-hydroxycinnamaldehydes in a mild, atom-economic N
      heterocyclic carbene-catalyzed redox lactonization. Corresponding coumarins are
      accessible via a one-pot domino oxidation lactonization procedure in the presence
      of oxidants.

PMID- 19170541
TI  - Nanoparticle-based solution deposition of gold films supporting bioresistant
      SAMs.
AB  - Thin films of gold on glass are prepared by solution deposition of functionalized
      gold nanoparticles followed by thermal treatment. The processed films adhere
      strongly to glass without any adhesion layers and can be
      micropatterned/microetched without delamination from the substrate. The formation
      of self-assembled monolayers (SAMs) of oligo(ethylene glycol) alkane thiols (EG
      SAMs) renders the films resistant to cell adhesion and allows for cell
      patterning.

PMID- 19170542
TI  - 1-Pyridine- and 1-quinuclidine-1-boraadamantane as models for derivatives of 1
      borabicyclo[2.2.2]octane. Experimental and theoretical evaluation of the B-N
      fragment as a polar isosteric substitution for the C-C group in liquid crystal
      compounds.
AB  - The suitability of 1-borabicyclo[2.2.2]octane (1) as a structural element for
      liquid crystals was evaluated using computational methods and experimental
      studies of two complexes of its close analogue 1-boraadamantane (2). The
      molecular and crystal structures for 1-pyridine-1-boraadamantane [2-P,
      C(14)H(20)BN, P2(1)/m, a = 8.4404(13) A, b = 6.8469(10) A, c = 10.5269(16) A,
      beta = 104.712(3) degrees, Z = 2], 1-quinuclidine-1-boraadamantane [2-Q,
      C(16)H(28)BN, P2(1)/n, a = 6.6529(3) A, b = 10.6665(6) A, c = 19.3817(10) A, beta
      = 94.689(3) degrees, Z = 4], and 1-pyridine-trimethylborane [3-P, C(8)H(14)BN,
      C(cma), a = 6.9875(10) A, b = 15.011(2) A, c = 16.556(2) A, Z = 8] were
      determined by X-ray crystallography and compared with the results of DFT and MP2
      calculations. Gas-phase thermodynamic stabilities of complexes 1-P, 1-Q, 2-P, and
      2-Q were estimated using a correlation between theoretical (MP2/6-31+G(d)//MP2/6
      31G(d) with B3LYP/6-31G(p) thermodynamic corrections) and experimental data for
      complexes of BMe(3) (3) with amines lacking N-H bonds. The analysis showed the
      generally higher thermodynamic stability for the quinuclidine (Q) complexes
      compared to that of the pyridine (P) analogues in the gas phase and an overall
      order of stability of 1 > 2 > 3. This order is paralleled by high ring strain
      energy of 1 (SE = 27 kcal/mol) as compared to that of 1-boraadamantane (2, SE =
      16.5 kcal/mol). The chemical stability of 2-P and 2-Q, with respect to hydrolytic
      and oxidative reagents, is high for the pyridine derivative and satisfactory for
      the quinuclidine complex at ambient temperature, which implies sufficiently high
      stability of 1-borabicyclo[2.2.2]octane complexes for materials applications.
      Molecular dipole moments of 6.2 +/- 0.1 and 6.0 +/- 0.15 D were measured for 2-Q
      and 2-P, respectively.

PMID- 19170543
TI  - X-ray diffraction study of ionic liquid based mixtures.
AB  - Crystal structures in N,N-diethyl-N-methyl-N-2-methoxyethylammonium
      tetrafluoroborate, [DEME][BF(4)], are determined by X-ray diffraction method. In
      [DEME][BF(4)]-based mixtures, various kinds of crystal structures and
      superstructures are induced by additives, i.e., H(2)O, CH(3)OH, C(2)H(5)OH, and
      C(6)H(6). Most of the crystal structures in the mixtures are related to that of
      pure [DEME][BF(4)], though unit cells in 1.1 and 6.1 mol % C(6)H(6) are different
      from the pure one. Further, [DEME][BF(4)]-C(6)H(6) mixtures require the two kinds
      of superstructures, where volume per [DEME][BF(4)] is contracted by a small
      amount of additives. Also, volume contraction and the coexistence of two kinds of
      superstructures are seen in 0.9 mol % H(2)O. The superstructures are derived from
      orientational or displacive modulations of [DEME][BF(4)] molecules. In spite of a
      small amount of additives, molecular interactions of [DEME][BF(4)] are influenced
      extensively.

PMID- 19170546
TI  - Octylglucopyranoside and cyclodextrin in water. Self-aggregation and complex
      formation.
AB  - At 25 degrees C ultrasonic attenuation spectra between 100 kHz and 400 MHz as
      well as sound velocities and densities of aqueous solutions of the surfactant n
      octyl-beta-d-glucopyranoside and of the cage compound alpha-cyclodextrin have
      been measured. The liquid system reveals a critical association concentration
      (cac) exceeding the cmc of the surfactant almost by the cyclodextrin
      concentration and thus indicating a significant formation of cyclodextrin
      surfactant inclusion complexes. The ultrasonic spectra display altogether four
      relaxation regions. The one with largest relaxation time (0.27 mus < or = tau(1)
      < or = 1.6 mus) exhibits a noticeable amplitude at surfactant concentrations
      larger than the cac only. It is assigned to the monomer exchange between the
      micelles and the suspending phase. A term with relaxation time tau(2) (33 ns < or
      = tau(2) < or = 135 ns) is characteristic for solutions containing both solutes.
      It is assumed to reflect the inclusion complex formation. Complexes with 1:1,
      2:1, and 1:2 stoichiometry appear to exist. The terms at higher frequencies (4.8
      ns < or = tau(3) < or = 9.8 ns; 0.8 ns <or = tau(4) < or = 2 ns) are due to
      fluctuations of the carbohydrate residues around the glucosidic bond angles and
      to the rotational isomerization of the exocyclic hydroxymethyl groups,
      respectively.

PMID- 19170545
TI  - The mechanisms of human hotdog-fold thioesterase 2 (hTHEM2) substrate recognition
      and catalysis illuminated by a structure and function based analysis.
AB  - The focus of this paper is the hotdog-fold thioesterase THEM2 from human (hTHEM2;
      Swiss-Prot entry Q9NPJ3 ). In an earlier communication (Cheng, Z., Song, F.,
      Shan, X., Wei, Z., Wang, Y., Dunaway-Mariano, D., and Gong, W. (2006) Crystal
      structure of human thioesterase superfamily member 2, Biochem. Biophys. Res.
      Commun. 349, 172-177) we reported the apo crystal structure of hTHEM2. Herein, we
      report the results of an extensive hTHEM2 substrate screen, the structure
      determination of hTHEM2 complexed with the inert substrate analogue undecan-2-one
      CoA (in which OC-CH(2)-S substitutes for OC-S) and the kinetic analysis of active
      site mutants. The work described in this paper represents the first reported
      structure-function based analysis of a human hotdog-fold thioesterase. The
      catalytic mechanism proposed involves the Asp65/Ser83 assisted attack of a water
      molecule at the Gly57/Asn50 polarized thioester CO and the Asn50 assisted
      departure of the thiolate leaving group. Thioesterase activity was observed with
      acyl-CoAs but not with the human acyl-ACP or with an acyl-Cys peptide. The medium
      to-long-chain fatty acyl-CoAs displayed the smallest K(m) values. The substrate
      specificity profile was analyzed within the context of the liganded enzyme to
      define the structural determinants of substrate recognition. Based on the results
      of this structure-function analysis we hypothesize that the physiological role of
      hTHEM2 involves catalysis of the hydrolysis of cytosolic medium-to-long-chain
      acyl-CoA thioesters.

PMID- 19170547
TI  - Self-assembly behavior of AB/AC diblock copolymer mixtures in dilute solution.
AB  - The self-assembly behavior of AB/AC amphiphilic diblock copolymer mixtures in
      dilute solution was studied by a real-space-implemented self-consistent field
      theory in three dimensions. The AB and AC copolymers have a common hydrophobic
      block A but different hydrophilic blocks B and C. Two cases were studied: one in
      which copolymers AB and AC have same hydrophobic and hydrophilic block lengths
      and one in which copolymers AB and AC have different hydrophobic and hydrophilic
      block lengths. It was found that the two copolymers can cooperatively self
      assemble into hybrid aggregates. The morphologies of the formed aggregates were
      found to be dependent on the mixture ratio and the interaction between the B and
      C blocks. For the AB/AC copolymers with different hydrophobic and hydrophilic
      lengths, chain segregation was found in the formed hybrid aggregates. Based on
      the obtained calculation results, phase diagrams as functions of the mixture
      ratio and interaction between the B and C blocks were constructed.

PMID- 19170548
TI  - Involvement of metals in enzymatic and nonenzymatic decomposition of C-terminal
      alpha-hydroxyglycine to amide: an implication for the catalytic role of enzyme
      bound zinc in the peptidylamidoglycolate lyase reaction.
AB  - The peptide C-terminal amide group essential for the full biological activity of
      many peptide hormones is produced by consecutive actions of peptidylglycine alpha
      hydroxylating monooxygenase (PHM) and peptidylamidoglycolate lyase (PAL); PHM
      catalyzes the hydroxylation of C-terminal glycine, and PAL decomposes the
      peptidyl-alpha-hydroxyglycine to an amidated peptide and glyoxylate. PAL contains
      1 mol of zinc, but its role, catalytic or structural, has not yet been clarified.
      In this study, we found that a series of transition metals, Mn(2+), Co(2+),
      Ni(2+), Cu(2+), Zn(2+), and Cd(2+), catalyze the nonenzymatic decomposition of
      the hydroxyglycine intermediate in a concentration-dependent manner. The second
      order rate constant of the metal catalysis increased with elevation of pH,
      indicating that the hydrated metal acts as a general base. Extensive removal of
      the enzyme-bound metals remarkably diminished the PAL activity; k(cat) of the
      metal-depleted enzyme retaining 0.1 mol of zinc decreased to 3.2 s(-1) from 25.7
      s(-1) of the wild-type enzyme. Among a series of divalent metals tested, Zn(2+),
      Co(2+), and Cd(2+) could fully restore the PAL activity of the metal-depleted
      enzyme. Especially, Zn substitution reproduced the steady-state parameters of the
      wild-type enzyme. On the other hand, Co and Cd substitution largely altered the
      kinetic parameters; the k(cat) increased 3- and 5-fold and the K(m) for the
      substrate increased 2.5- and 4-fold, respectively. These observations support
      that the enzyme-bound zinc plays a catalytic role, rather than a structural role,
      in the PAL reaction through the action of zinc-bound water as a general base.

PMID- 19170549
TI  - Organoactinide-mediated hydrothiolation of terminal alkynes with aliphatic,
      aromatic, and benzylic thiols.
AB  - Atom-efficient organoactinide-catalyzed intermolecular hydrothiolation of
      terminal alkynes is achieved by Th(IV) and U(IV) complexes to yield vinyl
      sulfides. The conversion is highly Markovnikov selective and is capable of
      utilizing aromatic, benzylic, and aliphatic thiols. Kinetic measurements of the
      transformation mediated by Me(2)SiCp(2)''Th[CH(2)(TMS)](2) (1a; Cp'' = eta(5)
      Me(4)C(5)) shows the reaction is zero-order in [thiol], first-order in [1a],
      first-order in [alkyne] at lower alkyne concentrations, and zero-order at higher
      [alkyne]. The proposed catalytic cycle invokes turnover-limiting insertion of the
      alkyne into the Th-S bond followed by a rapid Th-C bond protonolysis. All
      reactions except entries 7 and 8 are quantitative by (1)H NMR.

PMID- 19170550
TI  - The ultimate strength of glass silica nanowires.
AB  - In the past decade nanowires have attracted an increase interest because of their
      extraordinary mechanical strength. In fact, material properties in the nanoregime
      are extremely different from those found in macroscopic samples: few crystalline
      materials have shown a tensile strength in excess of 10 GPa in the form of
      nanowires. Still the length of defect-free crystalline nanowires is limited to a
      few millimeters and the strength of long nanowires is compromised by defects. The
      strength of glass nanowires is less affected by single defects. In this paper we
      present the ultimate strength of glass silica nanowires manufactured by a top
      down fabrication technique; this is the highest value reported for glass
      materials. The measured ultimate strength is in excess of 10 GPa and increases
      for decreasing nanowire diameters. Scanning electron micrographs of the broken
      fragments showed a fragile rupture.

PMID- 19170551
TI  - Multifunctional cytotoxic stealth nanoparticles. A model approach with potential
      for cancer therapy.
AB  - Here we report on a highly versatile nanoparticle-based core/shell drug delivery
      system consisting of cytotoxic stealth carrier particles. Their multifunctional
      shells, mandatory for addressing different diagnostic/treatment requirements, are
      constructed using a single assembly process in which various different
      functionalities are incorporated in a modular fashion. More specifically, we
      discuss a robust electrostatic and covalent layer-by-layer (LBL) assembly
      strategy as engineering approach toward nanoparticles with multilayer shells that
      combine all of the following properties: (i) a small size distribution of the
      nanoparticle carrier, (ii) a high stability in physiological media, (iii)
      attachment of a pro-drug in covalent form and thus a low toxicity of the carrier
      system, (iv) the triggered release and activation of the drug only after
      endocytosis and enzymatic cleavage, and (v) "stealthiness" and thus protection
      against uptake by macrophages. The fact that we employ small nanoparticles as
      carriers is predicted to enhance the accumulation of active drug in the tumor
      tissue (i.e., enhanced permeability and retention of tumor tissues, EPR). To
      establish this system as a proof of concept, we use the smallest nanoparticles
      within the interesting size range of about 25-100 nm for EPR targeting since
      these are the most difficult to functionalize and because they possess the
      highest surface area. On the basis of gold nanoparticle cores, our system allows
      for precise control of particle size and size distribution and also for easy
      monitoring of the dispersion stability by the naked eye.

PMID- 19170552
TI  - Molecular basis for the pH dependent structural transition of Nitrophorin 4.
AB  - Allostery can be defined in a broad sense as a structural change in a protein.
      The theoretical framework for allostery includes several formulations. In the
      stereochemical view, the activation event causes a local conformational change
      that is propagated through residue-to-residue contacts to the rest of the protein
      through well-defined structural pathways. The thermodynamic, or population shift
      model, instead implies that the "activated conformation" is already present with
      non-negligible population in the nonactivated conformational ensemble, and
      therefore the activation merely shifts the equilibrium. Nitrophorins (NPs) are
      heme proteins that store and transport NO in a pH dependent manner, due to a
      conformational change. Using MD simulations, we show that the NP structural
      transition occurs in two different conformational free energy landscapes, each
      one corresponding to a pH condition and characterized by specific residue-residue
      interactions that characterize them. We also show that when the protonation state
      of the equilibrium state is modified the conformation becomes unstable and
      proceeds very fast to an intermediate stable state that is different for each pH
      condition. Finally, we will discuss that allosteric transition in NP4 does not
      occur due to a change in the relative population of both end states, but due to a
      drastic change in the free energy landscape of its conformational ensemble.

PMID- 19170553
TI  - Ultradense synthetic gene brushes on a chip.
AB  - Dense brushes of linear DNA polymers are assembled on a biochip with
      approximately 30 nm between anchorage points, amounting to a few mega-base
      pairs/microm(3). In bulk solution, a barrier incurs to conjugate more than two
      end-functionalized DNAs. However, such doublets bind the surface with almost
      equal efficiency to singlets, suggesting that extended brush buildup reduces the
      barrier. On-chip transcription reveals that doublets are roughly 2-fold
      inefficient compared to singlets, a manifestation of the interaction of the
      enzymatic machinery with the dense brush. Synthetic gene brushes made of DNA
      conjugates provide simple means to regulate expression on a chip.

PMID- 19170554
TI  - Background suppression in near-field optical imaging.
AB  - In several recent studies, antenna-based optical microscopy has demonstrated its
      potential to resolve features as small as 10 nm. Most studies are concerned with
      well-separated features on flat surfaces, and there are only few studies that
      deal with samples of high feature density or even three-dimensional objects. The
      reason is that the external laser irradiation of the optical antenna (e.g., tip
      or particle) also directly irradiates the sample and therefore gives rise to a
      background. Here we introduce an efficient background suppression scheme that
      makes use of feedback modulation. The method is widely applicable and not
      restricted to cantilever-based scanning schemes. We apply this technique to both
      dense samples of dye molecules and ion channel proteins in plasma membranes and
      demonstrate effective background suppression and strongly improved sensitivity.
      The feedback modulation scheme is expected to find application for biological
      studies in liquid environments and for investigations of subsurface features in
      material science.

PMID- 19170555
TI  - Engineered macroporosity in single-wall carbon nanotube films.
AB  - A key advantage of bulk nanoscale materials in applications ranging from energy
      storage to chemical catalysis is their inherent high surface area. Single-wall
      carbon nanotube films possess the additional advantages of high electrical
      conductivity and robust mechanical integrity. Nevertheless the flexibility of the
      individual nanotubes and their affinity for each other conspire to obstruct the
      porosity in such films limiting the perfusion rate of liquids and gases,
      restricting the accessible surface area and thereby limiting their utility in
      important applications. Here we demonstrate a simple, effective means to engineer
      controlled porosity into the nanotube films. The newly incorporated porosity
      modifies the film electrolytic capacitance and comparative perfusion rates.
      Pseudocapacitive RuO(2) electrodeposited onto the highest porosity films exhibits
      a specific capacitance of 1084 F/g. Knowledge of the underlying nanotube
      capacitance and mass permits extraction of the deposited RuO(2) specific
      capacitance of 1715 F/g, which closely approaches the predicted theoretical
      maximum RuO(2) capacitance of 2000 F/g.

PMID- 19170556
TI  - Nanostructures and surface hydrophobicity of self-assembled thermosets involving
      epoxy resin and poly(2,2,2-trifluoroethyl acrylate)-block-poly(ethylene oxide)
      amphiphilic diblock copolymer.
AB  - Poly(2,2,2-trifluoroethyl acrylate)-block-poly(ethylene oxide) (PTFEA-b-PEO)
      amphiphilic diblock copolymer was synthesized via the reversible addition
      fragmentation transfer polymerization of 2,2,2-triffluroethyl acrylate with
      dithiobenzoyl-terminated poly(ethylene oxide) as a chain-transfer agent. The
      amphiphilic diblock copolymer was incorporated into epoxy resin to prepare the
      nanostructured epoxy thermosets. The nanostructures were investigated by means of
      atomic force microscopy, small-angle X-ray scattering, and dynamic mechanical
      analysis. In terms of the miscibility of the subchains of the block copolymer
      with epoxy after and before curing reaction, it is judged that the formation of
      the nanostructures follows the mechanism of self-assembly. The static contact
      angle measurements indicate that the nanostructured thermosets containing PTFEA-b
      PEO diblock copolymer displayed a significant enhancement in surface
      hydrophobicity as well as a reduction in surface free energy. The improvement in
      surface properties was ascribed to the enrichment of the fluorine-containing
      subchain (i.e., PTFEA block) of the amphiphilic diblock copolymer on the surface
      of the nanostructured thermosets, which was evidenced by surface atomic force
      microscopy and energy-dispersive X-ray spectroscopy.

PMID- 19170557
TI  - Magnetotransport in Co-doped ZnO nanowires.
AB  - Electrical and magnetotransport measurements were performed on individual Co
      doped ZnO dilute magnetic semiconductor nanowires. The electron transport studies
      show that the electron mobility could be as high as 75 cm(2)/(V.s), and we
      observed positive magnetoresistivity (MR) at low magnetic field and negative MR
      at higher magnetic field. s-d exchange-induced spin splitting of the conduction
      band could account for positive MR while suppression of weak localization of
      impurity centers could account for the negative MR. Lowering the carrier
      concentration in these nanowires through the application of a gate voltage tends
      to induce a larger magnitude MR as well as additional fine structure in the MR
      curves.

PMID- 19170558
TI  - PlasMOStor: a metal-oxide-Si field effect plasmonic modulator.
AB  - Realization of chip-based all-optical and optoelectronic computational networks
      will require ultracompact Si-compatible modulators, ideally comprising
      dimensions, materials, and functionality similar to electronic complementary
      metal-oxide-semiconductor (CMOS) components. Here we demonstrate such a
      modulator, based on field-effect modulation of plasmon waveguide modes in a MOS
      geometry. Near-infrared transmission between an optical source and drain is
      controlled by a gate voltage that drives the MOS into accumulation. Using the
      gate oxide as an optical channel, electro-optic modulation is achieved in device
      volumes of half of a cubic wavelength with femtojoule switching energies and the
      potential for gigahertz modulation frequencies.

PMID- 19170559
TI  - Chemical Changes in Liquid Benzene Multiply Shock Compressed to 25 GPa.
AB  - Shock wave experiments utilizing stepwise-loading, with peak stresses ranging
      between 4 and 25 GPa, were performed to examine the dynamic high pressure
      response of liquid benzene at thermodynamic conditions not attainable in single
      shock experiments. Time-resolved Raman spectroscopy was used to monitor the
      molecular and chemical changes on sub-mus time scales. Up to 20 GPa, the Raman
      modes showed pressure-induced shifting and broadening but no indication of a
      chemical change. At 24.5 GPa, however, the Raman modes become indistinguishable
      from an increasing background within 40 ns after the sample attained peak
      pressure, indicating a chemical change. A thermodynamically consistent equation
      of state (EOS) was developed to calculate the relevant thermodynamic variables in
      multiply shock compressed liquid benzene. Idealized molecular configurations were
      used in combination with the thermodynamic quantities in the shocked state to
      calculate the intermolecular separation between benzene molecules and to
      ascertain the likelihood of pi-orbital overlap. These idealized calculations show
      that sufficient energy and pi-orbital overlap exist in multiply shock compressed
      liquid benzene to permit intermolecular bonding at 24.5 GPa. Analysis of the
      Raman spectra, using the thermodynamic and intermolecular separation
      calculations, suggests that benzene undergoes polymerization through
      cycloaddition reactions. The rapid rate of polymerization is attributed to the
      benzene remaining in a liquid state on the sub-mus experimental time scale. The
      results from the present work demonstrate the importance of time, pressure,
      temperature, and phase in chemical changes associated with pi-bonded molecules.

PMID- 19170560
TI  - Variations in the quantum efficiency of multiple exciton generation for a series
      of chemically treated PbSe nanocrystal films.
AB  - We study multiple exciton generation (MEG) in two series of chemically treated
      PbSe nanocrystal (NC) films. We find that the average number of excitons produced
      per absorbed photon varies between 1.0 and 2.4 (+/-0.2) at a photon energy of
      approximately 4E(g) for films consisting of 3.7 nm NCs and between 1.1 and 1.6
      (+/-0.1) at hnu approximately 5E(g) for films consisting of 7.4 nm NCs. The
      variations in MEG depend upon the chemical treatment used to electronically
      couple the NCs in each film. The single and multiexciton lifetimes also change
      with the chemical treatment: biexciton lifetimes increase with stronger inter-NC
      electronic coupling and exciton delocalization, while single exciton lifetimes
      decrease after most treatments relative to the same NCs in solution. Single
      exciton lifetimes are particularly affected by surface treatments that dope the
      films n-type, which we tentatively attribute to an Auger recombination process
      between a single exciton and an electron produced by ionization of the dopant
      donor. These results imply that a better understanding of the effects of surface
      chemistry on film doping, NC carrier dynamics, and inter-NC interactions is
      necessary to build solar energy conversion devices that can harvest the multiple
      carriers produced by MEG. Our results show that the MEG efficiency is very
      sensitive to the condition of the NC surface and suggest that the wide range of
      MEG efficiencies reported in the recent literature may be a result of
      uncontrolled differences in NC surface chemistry.

PMID- 19170561
TI  - Vacuum-ultraviolet photoionization measurement and ab initio calculation of the
      ionization energy of gas-phase SiO2.
AB  - In this work we report on the detection and vacuum-ultraviolet (VUV)
      photoionization of gas-phase SiO(2) generated in situ via laser ablation of
      silicon in a CO(2) molecular beam. The resulting species are investigated by
      single-photon ionization with tunable VUV synchrotron radiation and mass analyzed
      using reflectron mass spectrometry. Photoionization efficiency (PIE) curves are
      recorded for SiO and SiO(2), and ionization energy estimates are revealed from
      such measurements. A state-to-state ionization energy of 12.60 +/- 0.05 eV is
      recorded by fitting two prominent peaks in the PIE curve for the following
      process: (1)Sigma O-Si-O --> (2)Pi(g) [O-Si-O](+). Electronic structure
      calculations aid in the interpretation of the photoionization process and allow
      for identification of the symmetric stretch of (2)Pi(g) [O-Si-O](+), which is
      observed in the PIE spectrum to be 0.11 eV (890 cm(-1)) above the ground state of
      the cation and agrees with the 892 cm(-1) symmetric stretch frequency calculated
      at the CCSD(T)/aug-cc-pVTZ level.

PMID- 19170562
TI  - Average local ionization energies in the Hartree-Fock and Kohn-Sham theories.
AB  - We explore the connection between average local ionization energies computed
      within the Hartree-Fock (HF) and the Kohn-Sham (KS) frameworks, focusing on
      exchange-only KS theory. We find that they are connected through a local quantity
      for which good approximations exist; I(HF)(r) = I(KS)(r) + DeltaV(X)(r). This
      allows determination of HF local ionization energies from exchange-only KS
      calculations without utilizing a nonlocal potential. We also suggest interesting
      research directions that emerge during our analysis.

PMID- 19170563
TI  - Masked velocity map imaging: a one-laser-beam Doppler-free spectroscopic
      technique.
AB  - A novel spectroscopic technique has been developed which makes it possible to
      record Doppler-free resonance-enhanced multiphoton ionization (REMPI) spectra
      with just one laser beam. The approach simply involves masking the outer side of
      the phosphor screen under velocity map imaging conditions so that only those
      species having no velocity component parallel to the laser beam propagation
      direction are detected. The benefits of this method are demonstrated in
      spectroscopic characterization of highly translationally and rotationally excited
      CO fragments resulted from the 230 nm photolysis of OCS and acetone, yielding
      substantially improved values of the rotational constants for the B state (v'' =
      0) of the CO molecule. The resolving power and the state distribution analysis of
      reaction products are also demonstrated for room-temperature H atoms generated by
      dissociation of background hydrogen molecules and oxygen atom detected from the
      225.6 nm photolysis of ozone.

PMID- 19170564
TI  - Study of electronic defects in CdSe quantum dots and their involvement in quantum
      dot solar cells.
AB  - To enhance efficiencies of quantum dot CdSe/TiO(2) based solar cells,
      understanding of the space charge at the CdSe/TiO(2) interface is crucial. In
      this paper, the presence of a shallow acceptor in the CdSe quantum dots is found
      by means of a detailed impedance and Mott-Schottky (C(-2)-phi) study.
      Furthermore, it is clearly shown that this acceptor density decreases strongly
      with increasing quantum dot size. The presence of these defect states may give
      rise to Auger recombination in small quantum dots and therewith decrease the
      efficiency of quantum-dot-sensitized solar cells.

PMID- 19170565
TI  - Sn-free Ni-catalyzed reductive coupling of glycosyl bromides with activated
      alkenes.
AB  - A mild, stereoselective method for the Ni-catalyzed synthesis of alpha-C
      alkylglycosides is reported. This approach entails the reductive coupling of
      glycosyl bromides with activated alkenes at room temperature, with low alkene
      loading as an important feature. Diastereoselective coupling with 2-substituted
      acrylate derivatives was made possible through the use of 2,4-dimethyl-3-pentanol
      as a proton source.

PMID- 19170566
TI  - Hope and expectation in the psychotherapy of the long-term mentally ill.
AB  - Despite growing research on the treatment of severe mental illness, little
      attention is devoted to the internal experience of therapists who strain to ward
      off disillusionment and despair as they try to hold out hope and reconfigure
      expectations over a course of therapy that may extend many years. The first
      person literature of recovery points repeatedly to the importance of maintaining
      faith in the face of resignation, yet much less appears in the professional
      literature about the struggles of therapists who live with apprehensions about
      the meaning of their work. The relative disappearance of commentary about this
      phenomenon, a legacy of the biological revolution in psychiatry, shields
      practitioners from self-examination and prevents a more penetrating look at the
      inner workings of psychotherapy in the treatment of long-term mental illness.

PMID- 19170567
TI  - Self-regulation and internal resources in school-aged children with ADHD
      symptomatology: an investigation using the Rorschach inkblot method.
AB  - This study assesses the capacity for emotional self-regulation and internal
      resources in a sample of urban children with ADHD symptomatology using the
      Rorschach Inkblot Method (RIM). Because these children have profound difficulty
      with modulating their affect, it is hypothesized that this difficulty would be
      reflected on RIM variables that have traditionally been thought to reflect the
      internal resources necessary for these children to regulate emotions. Children
      with greater ADHD symptoms were found to display lower scores on variables
      indicating internal resources for emotional self-regulation and stress tolerance
      (M, EA) relative to a comparison group with fewer ADHD symptoms. The research and
      clinical implications of these findings are discussed.

PMID- 19170568
TI  - Mind-brain and consciousness in psychoanalysis.
AB  - Understanding how the brain produces conscious mentation is vital to the
      prospective integration of psychoanalytic and neuroscientific study of the mind
      brain relation. This essay explores some of the current opinions, based on recent
      neuroscientific research, regarding origins of consciousness in the brain. Areas
      explored include levels of consciousness, waking versus dream consciousness, and
      issues of consciousness and self-organization in split-brain studies. Some
      tentative suggestions are made regarding clinical implications of this
      perspective.

PMID- 19170571
TI  - Synthesis of a novel polyhydroxylated salicylic acid lactone framework.
AB  - The facile preparation of a novel 8-membered polyhydroxylated salicylic acid
      lactone from 2,6-dihydroxybenzoic acid and sodium thio-D-glucose is described.
      The key step involved a sodium hydride promoted intramolecular lactonization in
      the presence of excess TMSCl, which led to isolation of the "natural product
      like" lactone.

PMID- 19170572
TI  - Modulation of carbene spin state population through precursor photophysics.
AB  - Dicarbomethoxycarbene can be generated by photolysis of S-C sulfonium ylides
      derived from thiophene. By manipulating the thiophene (leaving group) portion of
      the ylide, the initial spin distribution of the carbenes can be strongly
      influenced. With certain carbene traps, product distributions from
      dicarbomethoxycarbene depend on the initial spin state distribution in which the
      carbene is generated and this is used as a means to report on the initial spin
      state distributions. This approach should be general for other carbenes generated
      from analogous precursors.

PMID- 19170573
TI  - Kinetic isotope effects in oxygen in the laboratory dehydration of magnesian
      minerals.
AB  - Laboratory studies of vacuum dehydration of Mg-O-H units in minerals and rocks
      reveal large kinetic isotope effects in oxygen, with light-isotope enrichment in
      the liberated water, and concomitant heavy-isotope enrichment in the residual
      solids. Application of the same techniques to a meteorite assemblage including
      hydrous magnesium silicates shows a much more complex behavior, probably due to
      isotopic heterogeneity inherited from processes on the meteorite parent body.
      Measurements of both the (17)O/(16)O variations and the (18)O/(16)O variations
      confirm theoretical predictions that slopes of three-isotope correlation lines
      are systematically larger for equilibrium isotope effects than for kinetic
      isotope effects.

PMID- 19170574
TI  - Synthesis, structural, and optical properties of stable ZnS:Cu,Cl nanocrystals.
AB  - Stable water-suspendable Cu+-doped ZnS nanocrystals (NCs) have been synthesized
      with mercaptopropionic acid (MPA) as a capping molecule. The nanocrystals have
      been characterized using a combination of experimental techniques including UV
      vis and photoluminescence (PL) spectroscopy, X-ray diffraction (XRD),
      transmission electron microscopy (TEM), inductively coupled plasma (ICP), and
      extended X-ray absorption fine structure (EXAFS). The UV-vis electronic
      absorption spectrum shows an excitonic peak at 310 nm, characteristic of quantum
      confined ZnS NCs. This excitonic peak does not change noticeably with Cu+ doping.
      XRD confirms the formation of ZnS nanocrystals, and the average size of the NCs
      has been determined to be around 6 nm by TEM. The incorporation of Cu+ into the
      ZnS is manifested as a substantial red-shift of the emission band in the PL
      spectra upon addition of Cu2+ that was reduced into Cu+ during the synthesis
      reaction. EXAFS data were obtained to confirm copper doping as well as determine
      the local structure about Cu+ and Zn2+ in the NCs. Fitting to the EXAFS data for
      Cu+ suggests that most Cu+ ions are located near the surface within the ZnS NCs
      and that a significant fraction may be in the form of CuS as found in bulk
      material. These combined optical and structural studies have provided important
      new insight into the relevant electronic energy levels and their correlation to
      the optical and structural properties of ZnS:Cu,Cl NCs. This has important
      implications in potential applications of this phosphor material for solid state
      lighting, imaging, and other photonic devices.

PMID- 19170575
TI  - Poly(amide imides) and poly(ether imides) containing 1,3,4-oxadiazole or pyridine
      rings: characterizations and optical properties.
AB  - Two series of new aromatic polyimides were synthesized from 2,5-bis(4
      aminophenyl)-1,3,4-oxadiazole and 2,5-diamino-pyridine and various
      diamidedianhydrides and dietherdianhydride via high-temperature polycondensation
      in N-methyl-2-pyrrolidinone. The structures of polymers were characterized by
      means of FTIR, (1)H NMR spectroscopy, and elemental analysis; the results showed
      an agreement with the proposed structure. The polymers exhibited high glass
      transition temperatures (T(g) = 199-290 degrees C) and high thermal stability
      with decomposition temperatures (T(d)) in the range of 437-510 degrees C. The
      optical properties, that is, absorption and photoluminescence (PL) of synthesized
      polymers, were investigated in solution and in solid state as a blend with inert
      poly(methyl methacrylate) (PMMA). The polymers in solution emitted violet-blue
      light in the range of 417-453 nm depending on the polymer structure. The polymers
      containing pyridine rings in the backbone emitted light at a longer wavelength
      than polymers with oxadiazole units. The effect of solvent polarity on polymer
      emission was found. Additionally, the photoluminescence properties of the
      polymers before and after protonation with HCl were tested.

PMID- 19170576
TI  - Photodissociation dynamics of N-methylindole, N-methylpyrrole, and anisole.
AB  - Photodissociation experiments employing molecular beams of N-methylindole, N
      methylpyrrole, and anisole at 193 and 248 nm, respectively, have been conducted
      using multimass ion imaging techniques. We find that CH3 elimination is the sole
      dissociation channel for the studied molecules at both 193 and 248 nm. The
      photofragment translational energy distribution of anisole is found to contain
      both fast and slow components at the two wavelengths. On the other hand, a fast
      component (large recoil velocity) is dominant for N-methylindole at 248 nm, and a
      slow component (small recoil velocity) is dominant at 193 nm. The absorption
      coefficient of N-methylpyrrole is too weak for study at 248 nm. The photofragment
      translational energy distribution at 193 nm includes a large portion of the slow
      component and a small portion of the fast component. The findings indicate that
      the fast component corresponds to dissociation from the repulsive excited state
      and the slow component corresponding to dissociation from the ground electronic
      state. A comparison with the photodissociation dynamics of phenol, pyrrole, and
      indole suggests that replacement of the H atom by CH3 does not change the
      dissociation channels on the excited state. However, the respective dissociation
      channels for anisole and N-methylpyrrole on the ground state differ significantly
      from that for phenol and pyrrole.

PMID- 19170577
TI  - Three products are better than two: entropic advantages in the competing
      dissociation reactions of ionized azo-t-butane.
AB  - Ionized azo-t-butane (m/z 142) undergoes three dissociation reactions:
      competitive cleavage of the N-C bond to form (1) the t-butyl cation
      ((CH(3))(3)C(+), m/z 57) plus a neutral that is nominally (CH(3))(3)CN(2)(*) (85
      Da); (2) m/z 85 cation, (CH(3))(3)CN(2)(+), plus the neutral t-butyl radical; and
      (3) a minor rearrangement reaction leading to ionized butene. The competition
      between channels (1) and (2) is governed by both energetic and entropic
      considerations as the 85 Da neutral lies in a 1 kJ mol(-1) potential energy well
      and when formed dissociates into the t-butyl radical and N(2). This gives channel
      1 an entropic advantage over channel 2, as long as the transition states for
      these processes reside close to products, a conclusion supported by threshold
      photoelectron photoion coincidence spectroscopy, tandem mass spectrometry, and ab
      initio calculations.

PMID- 19170578
TI  - New chiral derivatizing agents: convenient determination of absolute
      configurations of free amino acids by 1H NMR.
AB  - The chiral carbonate reagents 5 allow for the direct and unambiguous
      determination of the absolute configurations of a wide range of free amino acids
      using (1)H NMR. By using a approximately 3:1 mixture of (S)-5 and (R)-5, absolute
      configurations of the corresponding carbamates are determined by only analyzing
      the nitrogen protons.

PMID- 19170579
TI  - Synthesis, transformations, and comparative studies of porphyryl acrylic acids
      and their homologues.
AB  - The reactivity of porphyryl acrylates and their homologues was studied
      systematically and to establish their potential as building blocks for the
      synthesis of novel tetrapyrroles. A new synthetic approach for multifunctional
      porphyrins was developed using alpha,beta-unsaturated acyl porphyrins as
      versatile building blocks with yields of 44-95%. The reaction of acyl chlorides
      generated in situ with ethyl diazoacetate in the presence of PPh(3) led to the
      corresponding phosphazine, which was quickly self-transformed into a novel
      porphyrin beta-keto ester system in up to 78% yield. Comparative studies of the
      next homologue of acrylic porphyrins, i.e., those bearing an additional CH(2)
      group next to the double bond of the alpha,beta-unsaturated fragment, showed that
      these can undergo rearrangement reactions via vinylketenes to yield both
      regioisomers. Depending on the reaction conditions, this method gives
      regioselectively access to either a rearrangement product or the product of
      esterification reactions in yields of 81% or 57%, respectively. Enyne metathesis
      of novel propargyl esters with allyl porphyrins provided an easy access to 1,3
      disubstituted butadienes in up to 76% yield.

PMID- 19170580
TI  - Understanding the role of intra- and intermolecular interactions in the formation
      of single- and double-helical structures of aromatic oligoamides: a computational
      study.
AB  - The generalized energy-based fragmentation (GEBF) approach has been implemented
      to extend the applications of density function theory (DFT) with empirical van
      der Waals (vdW) correction (Wu, Q.; Yang, W. T. J. Chem. Phys. 2002, 116, 515.)
      to large supramolecular systems with extensive pi-pi stacking interactions. This
      mixed approach, DFT(vdW)-GEBF, is applied to investigate the energies and
      structures of several aromatic oligoamide foldamers. Our calculations show that
      the formation of single helical structures is mainly driven by the stacking
      interaction between neighboring aromatic rings, further stabilized by the
      intramolecular hydrogen bonds of the backbone. The dimerization of two single
      helical strands to form the double helical structure is an energetically
      favorable process, which is mainly driven by extensive interstrand aromatic
      aromatic interactions. However, the dimerization energy tends to decrease
      significantly for longer oligomeric strands.

PMID- 19170581
TI  - Theory for protein folding cooperativity: helix bundles.
AB  - We present a theory for protein folding stability and cooperativity for helix
      bundle proteins. We treat the individual helices with a Schellman-Zimm-Bragg-like
      approach, using nucleation and propagation quantities, and we treat the
      hydrophobic and van der Waals contacts between the helices as a binding
      equilibrium. Predictions are in good agreement with experiments on both thermal
      and urea-induced transitions of (1) molecules that can undergo single helix-to
      coil transitions for various chain lengths and (2) three-helix-bundle proteins A
      and alpha3C. The present model addresses a problem raised by Kaya and Chan that
      proteins fold more cooperatively than previous models predict. The present model
      correctly predicts the experimentally observed two-state cooperativities,
      DeltaH(van't Hoff)/DeltaH(cal) approximately 1, for helix-bundle proteins. The
      predicted folding cooperativity is greater than that of helix formation alone, or
      collapse alone, because of the nonlinear coupling between the tertiary
      interactions and the helical interactions.

PMID- 19170582
TI  - Pharm.D.-only investigators are critical to the profession: let's preserve the
      fellowship as an equally important way to prepare future clinical pharmaceutical
      scientists: or the case against the "all-Ph.D.".

PMID- 19170583
TI  - Training clinical pharmaceutical scientists in today's highly competitive times:
      it's time to commit to change.

PMID- 19170584
TI  - Using secondary data sources for pharmacoepidemiology and outcomes research.
AB  - The increased availability of electronic medical records and administrative
      health care databases is adding to the popularity of pharmacoepidemiology and
      outcomes research studies. Despite their availability, practitioners may be
      reluctant to use these databases because they lack familiarity with database
      research in general. The basic principles of research are the same regardless of
      the data source, but there are a few special considerations. When using secondary
      data sources for research purposes, special care must be taken to select an
      appropriate source to ensure that relevant information is available to answer the
      research question at hand. Special attention must also be paid to selecting the
      appropriate codes to represent the outcomes and exposures of interest; therefore,
      a general understanding of coding schemes is necessary. Although time may be
      saved by not prospectively collecting data, the process of manipulating the data
      for analysis in secondary databases can be complex. Analysis of data from
      secondary sources may require special procedures to overcome the lack of
      randomization. By familiarizing themselves with these special issues,
      practitioners can use secondary sources to conduct studies that make valuable
      contributions to the improvement of patient care.

PMID- 19170585
TI  - Effects of monthly dose and regular dosing of intravenous active vitamin D use on
      mortality among patients undergoing hemodialysis.
AB  - STUDY OBJECTIVES: To determine if apparent protective mortality benefits of
      intravenous active vitamin D in patients undergoing hemodialysis extend across
      all groups defined by dialysis duration; if higher monthly dose and dosing
      regularity are associated with reduced mortality; and if intravenous active
      vitamin D use is associated with reduced cardiovascular, infectious, and cancer
      related mortality. STUDY DESIGN: Retrospective cohort study. DATA SOURCE: Centers
      for Medicare and Medicaid Services End-Stage Renal Disease database. PATIENTS: A
      total of 193,830 patients undergoing hemodialysis during 1999-2000, of whom
      94,208 (48.6%) were taking intravenous active vitamin D in the baseline period.
      MEASUREMENTS AND MAIN RESULTS: Time-varying Cox proportional hazards models were
      used to assess the effects of monthly vitamin D dose and dosing regularity over 3
      month intervals on risk of all-cause and cause-specific death, by dialysis
      duration groups (<1 yr, 1 to <3 yrs, 3 to <5 yrs, and >or=5 yrs from dialysis
      initiation). Models were adjusted for baseline characteristics, time-varying
      hospital days, monthly epoetin alfa dose, mean hemoglobin level, and urea
      reduction ratio in the 3-month intervals. Maximum follow-up time was 5.25 years.
      Adjusted all-cause mortality risk was reduced 7-17% among patients receiving
      vitamin D each month of the 3-month interval, with the highest reduction among
      patients with shorter dialysis duration. However, regular vitamin D dosing did
      not show consistent benefit across dialysis duration groups for cardiovascular,
      infectious, cancer, or other (all deaths not attributable to cardiovascular
      disease, infection, or cancer) mortality. CONCLUSION: Mortality benefits of
      intravenous vitamin D cannot be easily explained by currently proposed biologic
      mechanisms. Randomized controlled trials are needed to show definitively whether
      intravenous vitamin D can reduce all-cause and cause-specific mortality in
      patients undergoing dialysis compared with placebo.

PMID- 19170586
TI  - Rate of suicide in patients taking montelukast.
AB  - STUDY OBJECTIVE: To estimate the rate of suicide in patients taking montelukast.
      DESIGN: Population-based cohort study. DATA SOURCE: United Kingdom General
      Practice Research Database. PATIENTS: A total of 23,500 patients who had received
      at least one prescription for montelukast in the cumulative data from February
      1998-March 2007. MEASUREMENTS AND MAIN RESULTS: Rate of suicide was to be
      calculated as number of suicides divided by person-time at risk. Person-time of
      montelukast exposure was accrued for each patient as a cumulative duration of all
      prescriptions. The 23,500 patients had received 252,593 prescriptions for
      montelukast, representing 21,050 person-years at risk for suicide. We then sought
      to identify all cases that had a computer-recorded diagnosis of suicide; however,
      no cases of suicide were found in patients exposed to montelukast during our time
      frame. CONCLUSION: The risk of suicide attributable to montelukast, if present at
      all, is extremely low in users.

PMID- 19170587
TI  - Rivaroxaban: a novel, oral, direct factor Xa inhibitor.
AB  - Thromboembolic disorders such as deep vein thrombosis, pulmonary embolism,
      myocardial infarction, and stroke often result in long-term disability and/or
      mortality. The anticoagulants currently available have been effective in the
      treatment and prevention of these disorders; however, parenteral administration,
      variable pharmacokinetics and pharmacodynamics, drug and dietary interactions,
      and a requirement for frequent monitoring of efficacy and safety limit use of
      these drugs. Rivaroxaban is a novel, oral factor Xa inhibitor in clinical
      development for the treatment and prevention of thromboembolic diseases.
      Rivaroxaban is a small molecule directed at active sites, and the agent
      mechanistically differs from traditional anticoagulants, such as heparins and
      fondaparinux, in that its activity is independent of antithrombin and its ability
      to inhibit prothrombinase bound factor Xa. In addition, preclinical and clinical
      trial data indicate that rivaroxaban has predictable pharmacokinetics and
      pharmacodynamics, which are features that differentiate it from oral vitamin K
      antagonists. Phase II studies showed that rivaroxaban is safe and well tolerated
      across a wide range of doses. Furthermore, completed phase III studies
      demonstrated its efficacy in the prevention of venous thromboembolism after
      orthopedic surgery. Additional studies are now under way to evaluate the use of
      rivaroxaban in the treatment and prevention of other venous and arterial
      thromboembolic conditions.

PMID- 19170588
TI  - Diabetic retinopathy: current management and experimental therapeutic targets.
AB  - Diabetic retinopathy, a devastating ocular complication of diabetes mellitus, is
      the leading cause of blindness among working-age adults in the United States and
      is a serious public health problem throughout the world. Standard treatment is
      retinal laser photocoagulation, which is an invasive procedure with considerable
      limitations and adverse effects. Understanding the biochemical changes and
      molecular events that occur with diabetes as well as with retinopathy could lead
      to new and effective treatments. Research indicates an association between
      oxidative stress and the development of complications from diabetes, including
      retinopathy. Thus, many sites and sources of oxidative stress that may be
      involved in the development of diabetic retinopathy have been studied. However,
      in clinical trials, classic antioxidants have not been beneficial for patients
      with diabetes. Additional studies are needed to identify treatments that
      selectively target oxidative stress-mediated protein modification and thus
      prevent or at least delay diabetic retinopathy.

PMID- 19170589
TI  - Aliskiren: an oral direct renin inhibitor for the treatment of hypertension.
AB  - Aliskiren is the first member of the new class of orally active direct renin
      inhibitors to receive approval from the United States Food and Drug
      Administration for the treatment of hypertension. In patients with hypertension,
      aliskiren can be used either as monotherapy or in combination with other
      antihypertensive agents. By inhibiting renin, aliskiren blocks the conversion of
      angiotensinogen to angiotensin I, which subsequently results in a reduction in
      angiotensin II concentrations. Unlike the angiotensin-converting enzyme
      inhibitors and the angiotensin II receptor blockers (ARBs), which reactively
      stimulate an increase in plasma renin activity, aliskiren suppresses the effects
      of renin and leads to a reduction in plasma renin activity. In clinical trials
      involving patients with mild-to-moderate hypertension, aliskiren provided
      antihypertensive efficacy that was comparable to that of an ARB. Combination
      therapy with aliskiren and an ARB may provide additional blood pressure-lowering
      effects compared with the respective monotherapies with each of the agents. The
      results from surrogate outcome studies have also alluded to the potential for
      aliskiren to prevent target organ damage. Because aliskiren does not
      significantly affect the cytochrome P450 system, it has been associated with few
      drug interactions. In clinical studies, aliskiren was well tolerated, and its
      adverse-effect profile was similar to that of placebo. Fatigue, headache,
      dizziness, diarrhea, nasopharyngitis, and back pain were the most commonly
      reported adverse events. Overall, aliskiren appears to be a reasonable treatment
      option for patients with mild-to-moderate hypertension who are intolerant of
      first-line antihypertensive therapies. Aliskiren may also be a promising
      renoprotective strategy in patients with concomitant hypertension and diabetes
      mellitus. Its potential as a first-line antihypertensive agent will have to be
      further examined once studies evaluating its effects on long-term clinical
      outcomes are completed.

PMID- 19170590
TI  - Oxandrolone treatment in adults with severe thermal injury.
AB  - Severe thermal injury is associated with hypermetabolism and hypercatabolism,
      leading to skeletal muscle breakdown, lean body mass loss, weight loss, and
      negative nitrogen balance. Muscle protein catabolism in patients with severe
      thermal injury is the result of stress-induced increased release of cytokines and
      counterregulatory hormones. Coupled with decreased serum anabolic hormone
      concentrations such as testosterone and growth hormone along with the presence of
      insulin resistance, anabolism in patients with severe thermal injury is
      inefficient or impossible during the acute postburn period. This causes
      difficulty in restoring lean body mass and regaining lost body weight, as well as
      poor healing of the burn wound and delayed patient recovery. Oxandrolone, a
      synthetic derivative of testosterone, has been used in adult patients with severe
      thermal injury to enhance lean body mass accretion, restore body weight, and
      accelerate wound healing. In clinical studies, oxandrolone 10 mg orally twice/day
      improved wound healing, restored lean body mass, and accelerated body weight
      gain. During the rehabilitation period, oxandrolone therapy with adequate
      nutrition and exercise improved lean body mass, increased muscle strength, and
      restored body weight. However, most data on oxandrolone use in adult patients
      with severe thermal injury are derived from single-center studies, many of which
      enrolled a relatively small number of subjects and some of which had a poor
      design. Multicenter, prospective, randomized studies are needed to better define
      the optimal oxandrolone dosage and to confirm the efficacy and safety of this
      drug in adult patients with severe thermal injury.

PMID- 19170591
TI  - Daclizumab treatment for multiple sclerosis.
AB  - Multiple sclerosis is a chronic inflammatory and demyelinating disease of the
      central nervous system and the leading cause of neurologic disability in young
      adults. Established therapies, such as interferon and glatiramer, have only
      partial effects, and they offer limited or no effect on the progression of
      multiple sclerosis. The etiology of multiple sclerosis is unclear; however, the
      disease is presumed to be a T-cell-mediated autoimmune disease influenced by
      genetic and environmental factors. Therefore, targeting of lymphocytes may be a
      promising means of therapy for multiple sclerosis. Daclizumab is a humanized
      monoclonal antibody approved for use in preventing renal allograft rejection. The
      agent is under investigation in phase II trials for the treatment of multiple
      sclerosis and has demonstrated positive clinical outcomes, including decreased
      relapse rates. Adverse events included urinary tract infections, respiratory
      tract infections, paresthesias, mild leukopenia, transient elevations in liver
      enzyme and bilirubin levels, rash, postinfusion reactions (fever),
      lymphadenopathy, transient thrombocytopenia, and nausea. Daclizumab may be an
      alternative or add-on therapy when conventional immunomodulators fail or when
      existing approved therapies cannot be used. Besides ongoing phase II trials,
      additional phase II or III trials are required to determine the extended benefits
      of the agent, as well as clinical outcomes.

PMID- 19170592
TI  - Recommended education for pharmacists as competitive clinical scientists.

PMID- 19170593
TI  - Conformational changes triggered by Mg2+ mediate transactivator function.
AB  - Transactivator protein C of bacteriophage mu is essential for the transition from
      middle to late gene expression during the phage life cycle. The unusual,
      multistep activation of mom promoter (P(mom)) by C protein involves activator
      mediated promoter unwinding to recruit RNA polymerase and subsequent enhanced
      promoter clearance of the enzyme. To achieve this, C binds its site overlapping
      the -35 region of the mom promoter with a very high affinity, in Mg(2+)-dependent
      fashion. Mg(2+)-mediated conformational transition in C is necessary for its DNA
      binding and transactivation. We have determined the residues in C which
      coordinate Mg(2+), to induce allosteric transition in the protein, required for
      the specific interaction with DNA. Residues E26 and D40 in the putative metal
      binding motif (E(26)X(10)D(37)X(2)D(40)) present toward the N-terminus of the
      protein are found to be important for Mg(2+) ion binding. Mutations in these
      residues lead to altered Mg(2+)-induced conformation, compromised DNA binding,
      and reduced levels of transcription activation. Although Mg(2+) is widely used in
      various DNA transaction reactions, this report provides the first insights on the
      importance of the metal ion-induced allosteric transitions in regulating
      transcription factor function.

PMID- 19170594
TI  - Structural studies of a trinucleotide repeat sequence using 2-aminopurine.
AB  - The secondary structure of repeated trinucleotide sequences results in the
      development of several neurodegenerative diseases, and these studies consider the
      (CAG)(8) sequence that forms a stem-loop hairpin. The structural and
      thermodynamic properties of this hairpin are assessed using 2-aminopurine
      substitutions for adenine at six positions in this repeated sequence. Circular
      dichroism spectra and thermal denaturation experiments show that the secondary
      structure is not disturbed by the modifications. The local structure of the
      hairpin was monitored using the fluorescence intensities of 2-aminopurines, the
      changes in the intensity relative to the denatured state, and the sensitivity of
      the fluorescence to quenching by acrylamide. To establish the stem and loop
      characteristics in (CAG)(8), known reference points for stem, loop, and exposed
      base motifs were used. In the vicinity of the loop, the bases become more solvent
      exposed, which suggests that the instability associated with this repeated
      hairpin influences the global secondary structure. These results provide the
      basis to interpret the structures adopted by other repeated (CAG) structures.

PMID- 19170595
TI  - Safety assessment of drug metabolites: implications of regulatory guidance and
      potential application of genetically engineered mouse models that express human
      P450s.
AB  - Species differences in drug metabolism present two challenges that may confound
      the nonclinical safety assessment of candidate drugs. The first challenge is
      encountered when metabolites are formed uniquely or disproportionately in humans.
      Another challenge is understanding the human relevance of toxicities associated
      with metabolites formed uniquely or disproportionately in a nonclinical species.
      One potential approach to minimize the impact of metabolite related challenges is
      to consider genetically engineered mouse models that express human P450 enzymes.
      Human P450 expressing mouse models may have the ability to generate major human
      metabolites and eliminate or reduce the formation of mouse specific metabolites.
      Prior to determining the utility of any particular model, it is important to
      qualify by characterizing protein expression, establishing whether the model
      generates an in vivo metabolite profile more closely related to that of humans
      than the wild-type mouse, verifying genetic stability, and evaluating animal
      health. When compared to the current strategy for handling metabolite challenges
      (i.e., direct administration of metabolite), identifying an appropriate human
      P450 expressing model could provide a number of benefits. Such benefits include
      improved scientific relevance of the evaluation, decreased resource needs, and a
      possible reduction in the number of animals used. These benefits may ultimately
      improve the quality and speed by which promising new drug candidates are
      developed and delivered to patients.

PMID- 19170596
TI  - Protein folding rates and stability: how much is there beyond size?
AB  - An intriguing feature of protein folding is that the overall behavior obeys
      simple physical rules, but the finer details show a great deal of complexity. The
      scaling of thermodynamic and kinetic properties with protein size is one such
      rule. However, it is not clear to what extent biologically relevant folding
      properties (i.e., rates and stabilities) depend on size and/or on other factors
      such as structure and amino acid sequence. Here we address this question
      analyzing experimental data on 52 nonmultistate folding proteins with a simple
      theoretical model. We find that size scaling is the primary factor in determining
      folding rates, and more surprisingly also protein stability. Furthermore, our
      analysis reveals that the experimental deviations from size predictions are due
      to minute differences in the fundamental parameters (e.g., less than 2% for the
      stability). Folding is thus highly sensitive to little changes in protein
      energetics, but at the same time the folding properties of natural proteins are
      remarkably homogeneous. These results suggest that evolution has selected a small
      subset of possibilities from the physically plausible folding catalog and
      highlight the need for highly accurate protein force fields to predict rates and
      stabilities beyond general trends.

PMID- 19170597
TI  - Metabolic oxidative cleavage of thioesters: evidence for the formation of
      sulfenic acid intermediates in the bioactivation of the antithrombotic prodrugs
      ticlopidine and clopidogrel.
AB  - Metabolic cleavage of the CO-S bond of some thioesters RCOSR' with the formation
      of RCOOH requires a monooxygenase-dependent oxidative activation of this bond.
      The nature of the S-containing product(s) resulting from this cleavage remains
      unclear in most cases. This communication provides the first evidence for the
      formation of sulfenic acid intermediates 4a and 4b during the oxidative cleavage
      of the CO-S bond of thiolactone metabolites 2a and 2b of antithrombotic prodrugs,
      ticlopidine and clopidogrel, by rat and human liver microsomes. These
      intermediates have been trapped by dimedone, and the corresponding adducts 5a and
      5b have been characterized by mass spectrometry (MS) and (1)H and (13)C NMR
      spectroscopy. Their formation is monooxygenase-dependent and almost completely
      inhibited by microsomal cytochrome P450 inhibitors. Moreover, they were also
      formed upon incubation with microsomes containing recombinant human P450 3A4,
      3A5, 2C8, 2C9, 2C19, 2D6, or 1A2. In the presence of thiols such as
      mercaptoethanol, N-acetylcysteine, or glutathione, microsomal incubations of 2a
      led to mixed disulfides that have been characterized by MS and should result from
      reaction of 4a with these thiols. At high thiol concentrations, one observed in
      HPLC-MS the formation of a product exhibiting the MS expected for the previously
      described thiol metabolite 3a, a reduction product of 4a that has been reported
      as the pharmacologically active metabolite of ticlopidine. These data provide the
      first evidence for the formation of sulfenic acid reactive metabolites upon P450
      catalyzed oxidative cleavage of thioesters. They also provide a first detailed
      mechanism for the previously described formation of pharmacologically active
      thiols such as 3a upon oxidative metabolism of ticlopidine and clopidogrel.

PMID- 19170598
TI  - Discovery of novel arylethynyltriazole ribonucleosides with selective and
      effective antiviral and antiproliferative activity.
AB  - Novel ethynyltriazole ribonucleosides were synthesized using a simple and
      efficient two-step procedure involving Sonogashira coupling and subsequent
      ammonolysis. Compounds 2f and 3o inhibited hepatitis C virus (HCV) replication
      efficiently, whereas compound 3f demonstrated potent apoptosis-induced
      antiproliferative activity against pancreatic cancer MiaPaCa-2 cells both in
      vitro and in vivo. Most interestingly, the notable selective antiviral and
      antiproliferative activities were achieved respectively for 2f and 3f by
      modulating the ribose sugar moiety into deprotected and protected forms while
      retaining a similar trifluoromethylphenylethynyltriazole as the nucleobase.
      Preliminary structure-activity relationship study revealed that not only the
      ribose moiety but also the CF(3) group at the p-position of the phenyl ring and
      the rigid triple bond functionality contributed critically to the observed
      antiviral activity of 2f against HCV and antiproliferative activity of 3f against
      pancreatic cancer. These two compounds constitute therefore promising leads in
      the search for new antiviral and anticancer candidates.

PMID- 19170599
TI  - Transferring the concept of multinuclearity to ruthenium complexes for
      improvement of anticancer activity.
AB  - Multinuclear platinum anticancer complexes are a proven option to overcome
      resistance of established anticancer compounds. Transferring this concept to
      ruthenium complexes led to the synthesis of dinuclear Ru(II)-arene compounds
      containing a bis(pyridinone)alkane ligand linker. A pronounced influence of the
      spacer length on the in vitro anticancer activity was found, which is correlated
      to the lipophilicity of the complexes. IC(50) values in the same dimension as for
      established platinum drugs were found in human tumor cell lines. No cross
      resistance to oxoplatin, a cisplatin prodrug, was observed for the most active
      complex in three resistant cell lines; in fact, a 10-fold reversal of sensitivity
      in two of the oxoplatin-resistant lines was found. (Bio)analytical
      characterization of the representative examples showed that the ruthenium
      complexes hydrolyze rapidly, forming predominantly diaqua species that exhibit
      affinity toward transferrin and DNA, indicating that both proteins and
      nucleobases are potential targets.

PMID- 19170600
TI  - pH-responsive DNA-binding activity of Helicobacter pylori NikR.
AB  - Helicobacter pylori NikR (HpNikR) is a nickel-responsive transcription factor. In
      addition to a role in nickel homeostasis, HpNikR is proposed to serve as a master
      activator-repressor for H. pylori acid adaptation by directly or indirectly
      regulating the expression of a battery of genes. One potential mechanism of this
      regulation is modulation of the DNA-binding activity of HpNikR by the decrease in
      internal pH that occurs upon exposure to acidic shock. To test this hypothesis,
      several properties of HpNikR were investigated under acidic conditions. At pH
      5.8, the secondary and quaternary structures of the protein are not affected, and
      it still binds stoichiometric nickel in the same site, although with a slightly
      weaker affinity than that at pH 7.6. DNA-binding assays performed at pH 5.8
      reveal that, in contrast to pH 7.6, HpNikR binds to the ureA promoter in a nickel
      independent fashion. Binding to the nikR promoter at the lower pH is nickel
      dependent, however. Deletion of amino acids 3-11 of HpNikR abolished the nickel
      responsive activity and enhanced nonspecific DNA binding. Site-directed
      mutagenesis of HpNikR indicates that either Asp7 or Asp8 in the N-terminus of
      HpNikR plays a part in the activation of DNA binding. Furthermore, Lys6
      contributes selectively to complex formation with the nikR promoter sequence. The
      direct influence of pH on the activity of HpNikR may be critical to the role of
      this activator-repressor in the viability of H. pylori.

PMID- 19170601
TI  - Highly efficient formal synthesis of cephalotaxine, using the Stevens
      rearrangement--acid lactonization sequence as a key transformation.
AB  - Cephalotaxine (1), the major alkaloid isolated from Cephalotaxus species, has
      attracted considerable attention due to the promising antitumor activity of
      several of its derivatives and its unique structural features. Herein we describe
      a highly efficient formal synthesis of 1 employing the [2,3]-Stevens
      rearrangement-acid lactonization sequence as a key transformation from readily
      available (3,4-dimethoxyphenyl)acetic acid, methyl prolinate, and allyl bromide.

PMID- 19170602
TI  - Phosphorescence enhancement triggered by pi stacking in solid-state [Cu(N-N)(P
      P)]BF4 complexes.
AB  - In this article, we report a phosphorescence enhancement phenomenon of [Cu(N-N)(P
      P)]BF4 complexes in the solid state. The phosphorescence enhancement phenomenon
      is composed of three features: (1) an obvious emission blue shift, (2) a greatly
      enhanced photoluminescence quantum yield, and (3) a longer excited-state
      lifetime. Systematic analyses prove that the main cause of this phenomenon is
      nonradiative process suppression triggered by the pi stacking between [Cu(N-N)(P
      P)]BF4 molecules. The phosphorescence enhancement widely exists in [Cu(N-N)(P
      P)]BF4 complexes because of the pi surfaces in their diimine ligands.

PMID- 19170603
TI  - Isolable gold(I) complexes having one low-coordinating ligand as catalysts for
      the selective hydration of substituted alkynes at room temperature without acidic
      promoters.
AB  - Hydration of a wide range of alkynes to the corresponding ketones has been
      afforded in high yields at room temperature by using gold(I)-phosphine complexes
      as catalyst, with no acidic cocatalysts required. Suitable substrates covering
      alkyl and aryl terminal alkynes, enynes, internal alkynes, and propargylic
      alcohols, including enantiopure forms, are cleanly transformed to the
      corresponding ketones in nearly quantitative yields. Acid-labile groups present
      in the substrates are preserved. The catalytic activity strongly depends on both
      the nature of the phosphine coordinated to the gold (I) center and the softness
      of the counteranion, the complex AuSPhosNTf(2) showing the better activity. A
      plausible mechanism for the hydration of alkynes through ketal intermediates is
      proposed on the basis of kinetic studies. The described catalytic system should
      provide an efficient alternative to mercury-based methodologies and be useful in
      synthetic programs.

PMID- 19170604
TI  - Density functional theory and time-resolved resonance Raman investigation of the
      photocyclization of 2-pyridyl phenyl ketone in acid solution.
AB  - Density functional theory computations and nanosecond time-resolved resonance
      Raman (ns-TR(3)) spectroscopy experiments were done to study the photocyclization
      of 2-pyridyl phenyl ketone in acid solution. The most probable cyclization
      pathway was assigned to the reaction RX1, which had the lowest free-energy
      barrier. The factors that determine the free-energy barriers among the different
      reactions examined were discussed. Solvent effects on these reactions were also
      explored by calculations that included a polarizable continuum model for the bulk
      solvent effect.

PMID- 19170605
TI  - p-Nitrophenolate: a probe for determining acid strength in ionic liquids.
AB  - In order to obtain an acidity scale in room-temperature ionic liquid solutions,
      the protonation equilibrium of sodium p-nitrophenolate in [bm(2)im][NTf(2)] and
      in [bmpyrr][NTf(2)], at 298 K, has been studied by means of spectrophotometric
      titration. Carboxylic acids differing in both structure and in water solution
      strength have been used. Data collected indicate that in the analyzed ionic
      liquid solutions carboxylic acids are less dissociated than in water solution.
      Furthermore, by virtue of a mutual interaction, the studied equilibrium seems to
      be affected by both the nature of the ionic liquids and the carboxylic acids.

PMID- 19170606
TI  - Tuning of copper-loop flexibility in Bacillus subtilis CopZ copper chaperone:
      role of conserved residues.
AB  - Bacillus subtilis CopZ is a copper (Cu) chaperone that binds and delivers Cu to
      intracellular targets to maintain cellular Cu homeostasis. Like Cu chaperones
      from other organisms, including the human homologue Atox1, CopZ has the
      ferredoxin-like fold and binds Cu(I) via two Cys in a conserved
      M(11)X(12)C(13)X(14)X(15)C(16) motif located in a solvent-exposed loop. Here, we
      have performed extensive molecular dynamics simulations on strategic CopZ
      variants to reveal structural and dynamic roles of three residues near and in the
      Cu loop (i.e., Met11, Ser12, and Tyr65). Met11 is conserved in all Cu chaperones,
      whereas Ser12 and Tyr65 are exchanged for Thr and Lys in eukaryotes like Atox1.
      Therefore, our simulations included apo and holo forms of Met11Ala, Ser12Ala, and
      Tyr65Ala, as well as Ser12Thr and Tyr65Lys, CopZ variants. We have discovered
      that the conserved Met is solvent exposed and important for optimal Cu-loop
      flexibility in the apo form of CopZ but is buried in the core and aids in packing
      of the fold in holo-CopZ. Ser12 and Tyr65 are important for assuring Cu-loop
      flexibility in the apo form; in the Cu-bound form, these residues participate in
      stabilizing electrostatic networks. The two eukaryotic residues tested are not
      good substitutes for the prokaryotic counterparts in CopZ. By comparisons to data
      for Atox1, we conclude that common residues (like Met) and unique residues (like
      Ser12 and Tyr65 in CopZ) have evolved differentially in prokaryotic and
      eukaryotic Cu chaperones to tune the flexibility of the Cu loop of the apo form
      and to provide electrostatic Cu-site stabilization of the holo form.

PMID- 19170607
TI  - Probe for spin- and valence-selective X-ray absorption fine structure
      spectroscopy: EuLgamma4 emission.
AB  - EuLgamma(4) emission spectra of EuS, EuF(3), EuCl(3), and Eu(2)O(3) were measured
      using a multicrystal, multidetector spectrometer. Splitting of the EuLgamma(4)
      band was observed in the EuS spectra and attributed to exchange interactions
      between Eu5p and Eu4f. It was shown that because of this splitting, the
      EuLgamma(4) emission could be used for performing spin-selective measurements.
      This emission exhibited a large chemical shift (approximately 5 eV), depending on
      the valence state of a compound. The applicability of this emission to valence
      selective X-ray absorption fine structure spectroscopy was demonstrated through
      partial fluorescence yield measurements performed on a 1:1 mixture of EuS and
      Eu(2)O(3) and on a valence-fluctuating compound Eu(3)Pd(20)Ge(6).

PMID- 19170608
TI  - A unique insertion in the CP1 domain of Giardia lamblia leucyl-tRNA synthetase.
AB  - Leucyl-tRNA synthetase (LeuRS) catalyzes the esterification of the tRNA(Leu)
      isoacceptor with leucine. It contains a large insertion domain, connective
      peptide 1 (CP1), for amino acid editing. Here, we cloned the gene encoding LeuRS
      from Giardia lamblia (GlLeuRS), one of the most ancient eukaryotes. GlLeuRS was
      purified from an Escherichia coli overproduction strain, and its properties were
      investigated. The isolated CP1 domain of GlLeuRS (GlLeuRS-CP1) was an active
      protein for editing mischarged G. lamblia tRNA(Leu)(AAG) (GltRNA(Leu)). Insertion
      of 49 amino acid residues within the CP1 domain (the so-called 49-amino acid
      motif) was important for the optimal aminoacylation activity of GlLeuRS and was
      crucial for the editing capacity of GlLeuRS-CP1. Additionally, the motif can
      confer editing activity on the editing-defective isolated CP1 domain from E. coli
      LeuRS (EcLeuRS-CP1). We also found that GlLeuRS could not rescue a Saccharomyces
      cerevisiae leuS null strain, suggesting different recognition modes for these two
      LeuRSs with respect to tRNA(Leu).

PMID- 19170609
TI  - The transcriptional repressor RYBP is a natively unfolded protein which folds
      upon binding to DNA.
AB  - RYBP (Ring1A and YY1 binding protein) is a zinc finger protein with an essential
      role during embryonic development, which binds transcriptional factors, Polycomb
      products, and mediators of apoptosis, suggesting roles in, apparently, unrelated
      functions. To investigate mechanisms underlying its association with functionally
      diverse partners, we set out to study its structural properties using a number of
      biophysical (fluorescence, circular dichroism, Fourier transform infrared, and
      NMR spectroscopies) and hydrodynamic (analytical ultracentrifugation, DOSY-NMR,
      and gel filtration chromatography) techniques. We find RYBP to be a noncompact
      protein with little residual secondary structure, lacking a well-defined tertiary
      structure. These observations are also supported by theoretical calculations
      using neural networks and pairwise energy content, suggesting that RYBP is a
      natively unfolded protein. In addition, structural studies on its binding to the
      C-terminal region of the Polycomb protein Ring1B or to DNA show conformational
      changes in the complexed RYBP, consistent with the acquisition of a folded
      structure. The data provide a structural explanation for RYBP engagement in
      functionally unrelated pathways by means of its assembly into various
      macromolecular complexes as an unstructured protein with the ability to acquire a
      well-structured fold due to its association with different partners.

PMID- 19170610
TI  - Hydrophobic core of the steroidogenic acute regulatory protein for cholesterol
      transport.
AB  - The steroidogenic acute regulatory protein (StAR), the first family member of
      START (StAR-related lipid transport) proteins, plays an essential role by
      facilitating the movement of cholesterol from the outer to inner mitochondrial
      membrane. Wild-type and mutant StAR binds cholesterol with similar intensity, but
      only wild-type StAR can transport it to mitochondria. Here, we report that the
      hydrophobic core is crucial for biological activity of proteins with START
      domains. Wild-type StAR increased steroidogenic activity by 7-9-fold compared to
      mutant R182L StAR, but both of them showed similar near-UV CD spectra. The
      fluorescence maximum of wild-type StAR is red shifted in comparison to mutant
      StAR under identical urea concentration. TFE increased the alpha-helical
      contribution of wild-type StAR more than the mutant protein. Acrylamide quenching
      for the wild-type protein (K(SV) = 12.0 +/- 0.2-11.2 +/- 0.5 M(-1)) exceeded that
      of the mutant protein (K(SV) = 4 +/- 0.2 M(-1)). Consistent with these findings,
      the hydrophobic probe ANS bound wild-type StAR (K(app) = 8.1 x 10(5) M(-1)) to a
      greater degree than mutant StAR (K(app) = 3.75 x 10(5) M(-1)). Partial
      proteolysis examined by mass spectrometry suggests that only wild-type StAR has a
      protease-sensitive C-terminus, but not the mutant. Stopped-flow CD revealed that
      the time of unfolding of mutant StAR was 0.017 s. In contrast, the wild-type StAR
      protein is unfolded in 16.3 s. In summary, these results demonstrate that wild
      type StAR adopts a very flexible form due to the accommodation of more water
      molecules, while mutant StAR is generated by an alternate folding pathway making
      it inactive.

PMID- 19170612
TI  - Multicomponent polymeric film for red to green low power sensitized up
      conversion.
AB  - The realization of red to green photon energy up-conversion in a multicomponent
      polymeric organic solid film with good photochemical stability is presented. Up
      converted light is obtained by using an ultralow excitation power density in the
      range of 1 mW cm(-2), suitable to recover the low energy tail of the solar
      emission spectrum.

PMID- 19170613
TI  - Synergistic stabilization of nucleic acid assembly by 2'-O,4'-C-methylene-bridged
      nucleic acid modification and additions of comb-type cationic copolymers.
AB  - Stabilization of nucleic acid assemblies, such as duplex and triplex, is quite
      important for their wide variety of potential applications. Various stabilization
      methods, including molecular designs of chemically modified nucleotides and
      hybrid stabilizers, and combinations of different stabilization methods have been
      developed to increase stability of nucleic acid assemblies. However, combinations
      of two stabilizing methods have not always yielded desired synergistic effects.
      In the present study, to propose a strategy for selection of a rational
      combination of stabilizing methods, we demonstrate synergistic stabilization of
      triplex by 2'-O,4'-C-methylene-bridged nucleic acid (2',4'-BNA) modification of
      triplex-forming oligonucleotide and addition of poly(l-lysine)-graft-dextran
      copolymer [poly(l-lysine) grafted with hydrophilic dextran side chains]. Each of
      these methods increased the binding constant for triplex formation by nearly 2
      orders of magnitude. However, their kinetic contributions were quite distinct.
      The copolymer increased the association rate constant, whereas the 2',4'-BNA
      modification decreased the dissociation rate constant for triplex stabilization.
      The combination of both stabilizing methods increased the binding constant by
      nearly 4 orders of magnitude. Kinetic analyses revealed that the successful
      synergistic stabilization resulted from kinetic complementarity between increased
      association rate constants by the copolymer and decreased dissociation rate
      constants by the 2',4'-BNA modification. The stabilizing effect of one
      stabilization method did not alter that of the other stabilization method. We
      propose that kinetic analyses of each stabilizing effect permit selection of a
      rational combination of stabilizing methods for successful synergy in stabilizing
      nucleic acid assemblies.

PMID- 19170614
TI  - Electrical recording from hearts with flexible nanowire device arrays.
AB  - We show that nanowire field-effect transistor (NWFET) arrays fabricated on both
      planar and flexible polymeric substrates can be reproducibly interfaced with
      spontaneously beating embryonic chicken hearts in both planar and bent
      conformations. Simultaneous recordings from glass microelectrode and NWFET
      devices show that NWFET conductance variations are synchronized with the beating
      heart. The conductance change associated with beating can be tuned substantially
      by device sensitivity, although the voltage-calibrated signals, 4-6 mV, are
      relatively constant and typically larger than signals recorded by microelectrode
      arrays. Multiplexed recording from NWFET arrays yielded signal propagation times
      across the myocardium with high spatial resolution. The transparent and flexible
      NWFET chips also enable simultaneous electrical recording and optical
      registration of devices to heart surfaces in three-dimensional conformations not
      possible with planar microdevices. The capability of simultaneous optical imaging
      and electrical recording also could be used to register devices to a specific
      region of the myocardium at the cellular level, and more generally, NWFET arrays
      fabricated on increasingly flexible plastic and/or biopolymer substrates have the
      potential to become unique tools for electrical recording from other tissue/organ
      samples or as powerful implants.

PMID- 19170615
TI  - Carrier dynamics and quantum confinement in type II ZB-WZ InP nanowire
      homostructures.
AB  - We use time-resolved photoluminescence from single InP nanowires containing both
      wurtzite (WZ) and zincblende (ZB) crystalline phases to measure the carrier
      dynamics of quantum confined excitons in a type-II homostructure. The observed
      recombination lifetime increases by nearly 2 orders of magnitude from 170 ps for
      excitons above the conduction and valence band barriers to more than 8400 ps for
      electrons and holes that are strongly confined in quantum wells defined by
      monolayer-scale ZB sections in a predominantly WZ nanowire. A simple
      computational model, guided by detailed high-resolution transmission electron
      microscopy measurements from a single nanowire, demonstrates that the dynamics
      are consistent with the calculated distribution of confined states for the
      electrons and holes.

PMID- 19170616
TI  - DNA hairpins containing a diaminostilbene derivative as a photoinduced electron
      donor for probing the effects of single-base mismatches on excess electron
      transfer in DNA.
AB  - To investigate the effects of local structural disorder induced by a single-base
      mismatch on excess electron transfer (EET) in DNA, a novel hairpin DNA containing
      diaminostilbene (DAS) as a photoinducible electron donor has been developed. It
      was clearly demonstrated that EET efficiency depends on the electron injection
      modes from the electron donors and redox properties of the mismatched bases.

PMID- 19170617
TI  - Electrocatalytic formal [2+2] cycloaddition reactions between anodically
      activated aliphatic enol ethers and unactivated olefins possessing an
      alkoxyphenyl group.
AB  - Electrocatalytic formal [2+2] cycloadditions between anodically activated
      aliphatic enol ethers and unactivated olefins possessing an alkoxyphenyl group
      have been accomplished in a lithium perchlorate/nitromethane electrolyte
      solution. The alkoxyphenyl group was revealed to play an important role in the
      reaction intermediates to complete formation of the cyclobutane ring through
      intramolecular electron transfer between the cyclobutane radical cation and the
      alkoxyphenyl group.

PMID- 19170618
TI  - New benzotriazole and benzimidazole scaffolds from Ugi-Smiles couplings of
      isocyanides.
AB  - When allylamine is used as the amino input in Ugi-Smiles couplings of o
      nitrophenols, the resulting adducts can be deallylated by a palladium-catalyzed
      process leading to a formal Ugi-Smiles coupling with ammonia. This new sequence,
      combined with hydrogenolysis of the nitro group, offers an interesting
      multicomponent entry to benzotriazole and benzimidazole scaffolds.

PMID- 19170620
TI  - A convergent approach toward the C1-C11 subunit of phoslactomycins and formal
      synthesis of phoslactomycin B.
AB  - The preparation of the C1-C11 subunit of phoslactomycins, and a formal synthesis
      of phoslactomycin B, were achieved by a convergent strategy involving the
      chelation-controlled addition of an alkynyl Grignard reagent to an alpha-alkoxy
      ketone. Catalytic enantioselective reductions of acetylenic ketones and a [2,3]
      Wittig rearrangement were utilized as key steps to control the configuration of
      the C4, C5, and C9 stereocenters.

PMID- 19170619
TI  - Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for
      possible anticancer properties.
AB  - Recently, a convincing body of evidence has accumulated suggesting that the
      overexpression of carbonic anhydrase isozyme IX (CA IX) in some cancers
      contributes to the acidification of the extracellular matrix, which in turn
      promotes the growth and metastasis of the tumor. These observations have made CA
      IX an attractive drug target for the selective treatment of certain cancers.
      Currently, there is no available X-ray crystal structure of CA IX, and this lack
      of availability has hampered the rational design of selective CA IX inhibitors.
      In light of these observations and on the basis of structural alignment homology,
      using the crystal structure of carbonic anhydrase II (CA II) and the sequence of
      CA IX, a double mutant of CA II with Ala65 replaced by Ser and Asn67 replaced by
      Gln has been constructed to resemble the active site of CA IX. This CA IX mimic
      has been characterized kinetically using (18)O-exchange and structurally using X
      ray crystallography, alone and in complex with five CA sulfonamide-based
      inhibitors (acetazolamide, benzolamide, chlorzolamide, ethoxzolamide, and
      methazolamide), and compared to CA II. This structural information has been
      evaluated by both inhibition studies and in vitro cytotoxicity assays and shows a
      correlated structure-activity relationship. Kinetic and structural studies of CA
      II and CA IX mimic reveal chlorzolamide to be a more potent inhibitor of CA IX,
      inducing an active-site conformational change upon binding. Additionally,
      chlorzolamide appears to be cytotoxic to prostate cancer cells. This preliminary
      study demonstrates that the CA IX mimic may provide a useful model to design more
      isozyme-specific CA IX inhibitors, which may lead to development of new
      therapeutic treatments of some cancers.

PMID- 19170621
TI  - Photovoltaic performance of an ultrasmall band gap polymer.
AB  - A conjugated polymer (PBTTQ) that consists of alternating electron-rich
      bithiophene and electron-deficient thiadiazoloquinoxaline units was synthesized
      via Yamamoto polymerization with Ni(cod)(2) and provides a band gap of 0.94 eV.
      This represents one of the smallest band gaps obtained for a soluble conjugated
      polymer. When applied in a bulk heterojunction solar cell together with [84]PCBM
      as the electron acceptor, the polymer affords a response up to 1.3 microm.

PMID- 19170622
TI  - Nonlinear optical response and ultrafast dynamics in C60.
AB  - C(60) is a symbol of nanoscience. Its impact is far beyond the initial interest
      in this nanometer molecule itself. This paper reviews the current status of the
      nonlinear optical and ultrafast dynamics investigations of C(60). The review
      starts with the nonlinear optical response, in particular the dispersion spectra
      of harmonic generation and two-photon absorption. Both the experimental and
      theoretical challenges are highlighted. The main focus is on femtosecond and
      picosecond degenerate and nondegenerate four-wave mixing and pump-probe
      techniques as a tool to investigate ultrafast electron and nuclear dynamics,
      charge transfer and photoexcitation in C(60). Theoretical investigations are
      essential to understand these processes. Theory predicts a longer relaxation time
      for charge transfer than photoexcitation and reveals the underlying reasons for
      the normal mode excitations and changes in the electron density of states, which
      is directly linked to the time-resolved photoemission spectra. Theory also
      resolves a long-time puzzle about the dependence of normal mode excitations on
      the laser pulse duration and predicts that time-resolved pump-probe spectroscopy
      is able to probe electron correlation effects. Finally, high-harmonic generation
      in C(60) is reviewed. The review concludes with prospectives and possible
      applications.

PMID- 19170624
TI  - A modular synthesis of highly substituted imidazolium salts.
AB  - A versatile and modular one-pot method for the preparation of differently
      substituted symmetrical and unsymmetrical imidazolium salts is reported, and 19
      examples are given. In the key step, readily available formamidines and alpha
      halo ketones are coupled to give imidazolinium salts 3, followed by imidazolium
      salt formation by acylation-induced elimination. For many substitution patterns
      of the imidazolium salt products, this efficient strategy compares favorably with
      well-known processes in terms of yield, ease of synthesis, and robustness.

PMID- 19170628
TI  - Electronically nonadiabatic dynamics via semiclassical initial value methods.
AB  - In the late 1970s Meyer and Miller (MM) [J. Chem. Phys. 1979, 70, 3214.]
      presented a classical Hamiltonian corresponding to a finite set of electronic
      states of a molecular system (i.e., the various potential energy surfaces and
      their couplings), so that classical trajectory simulations could be carried out
      by treating the nuclear and electronic degrees of freedom (DOF) in an equivalent
      dynamical framework (i.e., by classical mechanics), thereby describing
      nonadiabatic dynamics in a more unified manner. Much later Stock and Thoss (ST)
      [Phys. Rev. Lett. 1997, 78, 578.] showed that the MM model is actually not a
      "model", but rather a "representation" of the nuclear-electronic system; i.e.,
      were the MMST nuclear-electronic Hamiltonian taken as a Hamiltonian operator and
      used in the Schrodinger equation, the exact (quantum) nuclear-electronic dynamics
      would be obtained. In recent years various initial value representations (IVRs)
      of semiclassical (SC) theory have been used with the MMST Hamiltonian to describe
      electronically nonadiabatic processes. Of special interest is the fact that,
      though the classical trajectories generated by the MMST Hamiltonian (and which
      are the "input" for an SC-IVR treatment) are "Ehrenfest trajectories", when they
      are used within the SC-IVR framework, the nuclear motion emerges from regions of
      nonadiabaticity on one potential energy surface (PES) or another, and not on an
      average PES as in the traditional Ehrenfest model. Examples are presented to
      illustrate and (hopefully) illuminate this behavior.

PMID- 19170630
TI  - Tetrapod-shaped colloidal nanocrystals of II-VI semiconductors prepared by seeded
      growth.
AB  - We report a general synthetic approach to tetrapod-shaped colloidal nanocrystals
      made of various combinations of II-VI semiconductors. Uniform tetrapods were
      prepared using preformed seeds in the sphalerite structure, onto which arms were
      grown by coinjection of the seeds and chemical precursors into a hot mixture of
      surfactants. By this approach, a wide variety of core materials could be chosen
      (in practice, most of the II-VI semiconductors that could be prepared in the
      sphalerite phase, namely, CdSe, ZnTe, CdTe); in contrast, the best materials for
      arm growth were CdS and CdTe. The samples were extensively characterized with the
      aid of several techniques.

PMID- 19170629
TI  - Valence anions of 9-methylguanine-1-methylcytosine complexes. Computational and
      photoelectron spectroscopy studies.
AB  - The photoelectron spectrum for the radical anion of 9-methylguanine-1
      methylcytosine, MGMC(-), was recorded for the first time. To interpret the
      experimental results, B3LYP/6-31++G(d,p) level computational studies were carried
      out for the neutral and anionic complexes of MGMC/MGMC(-) stabilized by three
      hydrogen bonds and comprising canonical or low-energy tautomeric forms of the
      methylated nucleobases. The visualization of singly occupied molecular orbitals
      for the MGMC(-) anions indicates that they are valence-bound species since the
      excess electron is localized on a pi* orbital of cytosine. All but one of the
      studied anionic complexes are adiabatically stable at the applied B3LYP level of
      theory. The intensity maximum of the broad band in the photoelectron spectrum was
      measured at 2.1 eV. This value is very well reproduced by the calculated vertical
      detachment energy of the calculated global minimum geometry of the MGMC(-) anion.
      This structure is the Watson-Crick base pair anion with proton transferred from
      the N1 atom of guanine to the N3 site of cytosine. The calculated adiabatic
      electron affinities span a range of 0.39-0.60 eV. The consequences of electron
      attachment to the AT or GC base pairs incorporated within DNA are briefly
      discussed in the context of DNA damage by low-energy electrons.

PMID- 19170631
TI  - Biomass characterization of Buddleja davidii: a potential feedstock for biofuel
      production.
AB  - A compositional analysis was performed on Buddleja davidii to determine its
      general biomass characteristics and provide detailed analysis of the chemical
      structures of its cellulose and lignin using NMR. B. davidii is a new potential
      lignocellulosic bioresource for producing bioethanol because it has several
      attractive agroenergy features. The biomass composition of B. davidii is 30%
      lignin, 35% cellulose, and 34% hemicellulose. Solid-state CP/MAS (13)C NMR showed
      that 33% of the cellulose is para-crystalline and 41% is at inaccessible
      surfaces. Both quantitative (13)C and (31)P NMR were used to examine the
      structure of lignin. The lignin was determined to be guaiacyl and syringyl with
      an h:g:s ratio of 0:81:19.

PMID- 19170632
TI  - Production of free amino acids and gamma-aminobutyric acid by autolysis reactions
      from wheat bran.
AB  - To find added value for wheat-milling byproduct, an approach for producing free
      amino acids and gamma-aminobutyric acid (GABA) was examined. Milled whole grain,
      bran, shorts, red dog, and 60% extracted flour all released amino acids using a
      water-soaking treatment. Little difference was found in amino acid production
      yield from whole grain between the soft and hard wheat cultivars investigated.
      Among the milled fractions, shorts produced the largest amount of total amino
      acids followed by bran, red dog, and 60% extracted flour in decreasing order.
      From the byproduct fraction (mixture of bran and shorts), leucine (Leu), arginine
      (Arg), valine (Val), lysine (Lys), glutamine (Gln), phenylalanine (Phe),
      isoleucine (Ile), and GABA were produced at 486, 421, 316, 329, 321, 279, 227,
      and 118 mg/100 g, respectively, in 120 h at 40 degrees C. Optimal pH for the
      byproduct fraction was 3.5-5.0 for alpha-amino acids and 5.5 for GABA. The
      production levels rose with increasing temperature up to 40-50 degrees C for
      alpha-amino acids and up to 40 degrees C for GABA. The yield of all amino acids
      increased in the experimented period until 120 h except for aspartic acid (Asp)
      and asparagine (Asn). Thus, wheat-milling byproducts have the potential to become
      effective materials for developing foods enriched in branched-chain amino acids
      (BCAA), Arg, Lys, Gln, Phe, and GABA.

PMID- 19170633
TI  - Computational studies of epidermal growth factor receptor: docking reliability,
      three-dimensional quantitative structure-activity relationship analysis, and
      virtual screening studies.
AB  - An aberrant activity of the epidermal growth factor receptor (EGFR) has been
      shown to be related to many human cancers, such as breast and liver cancers, thus
      making EGFR an attractive target for antitumor drug discovery. In this study we
      evaluated the reliability of various kinds of docking software and procedures to
      predict the binding disposition of EGFR inhibitors. By application of the best
      procedure and use of more than 200 compounds, a receptor-based 3D-QSAR model for
      EGFR inhibition was developed. On the basis of the results obtained, the
      possibility of developing virtual screening studies was also evaluated. The VS
      procedure that proved to be the most reliable from a computational point of view
      was then used to filter the Maybridge database in order to identify new EGFR
      inhibitors. Enzymatic assays revealed that among the eight top-scoring compounds,
      seven proved to inhibit EGFR activity at a concentration of 100 microM, two of
      them exhibiting IC(50) values in the low micromolar range and one in the
      nanomolar range. These results demonstrate the validity of the methodologies
      followed. Furthermore, the two low micromolar compounds may be considered as very
      interesting leads for the development of new EGFR inhibitors.

PMID- 19170634
TI  - Functionality of gliadin proteins in wheat flour tortillas.
AB  - Gliadins are monomeric proteins that are encoded by the genes at the loci Gli 1
      and Gli 2 present on the short arm of homologous wheat chromosomes 1 and 6,
      respectively. Studies have suggested that gliadins may play an important role in
      determining the functional properties of wheat flour. The main objective of this
      study was to understand the functionality of gliadins with respect to tortilla
      quality. The important tortilla quality attributes are diameter, opacity, and
      shelf stability, designated here as rollability or the ability to roll or fold
      the tortilla without cracking. In this study gliadin functionality in tortilla
      quality was studied using near-isogenic wheat lines that have deletions in either
      Gli A1, Gli D1, Gli A2, or Gli D2 gliadin loci. The deletion lines are designated
      by the same abbreviations. Dough and tortillas were prepared from the parent line
      used to derive these deletion lines, each individual deletion line, and a control
      commercial tortilla flour. Quantitative and qualitative evaluations were
      performed on the dough and tortillas derived from the flour from each of these
      lines. None of the deletions in the gliadin loci altered the shelf stability
      versus that found for the parent to the deletion lines or control tortilla flour.
      However, deletions in the Gli 2 loci, in particular Gli A2 reduced the relative
      proportion of alpha- and beta-gliadins with a greater cysteine amino acid content
      and gluten cross-link function versus the chain-terminating omega-gliadins in Gli
      1, which were still present. As such, the dough and gluten matrix appeared to
      have greater extensibility, which improved the diameter and overall quality of
      the tortillas while not altering the rollability. Deletions in the Gli 1 loci had
      the opposite result with increased cross-linking of alpha- and beta-gliadins,
      polymeric protein content, and a stronger dough that decreased the diameter and
      overall quality of the tortillas. The data suggest that altering certain Gli 2
      loci through null alleles could be a viable strategy to develop cultivars
      improved for the specific functionality requirements needed for the rapidly
      growing tortilla market.

PMID- 19170635
TI  - Effect of pH, salt, and biopolymer ratio on the formation of pea protein isolate
      gum arabic complexes.
AB  - Turbidity measurements were used to study the formation of soluble and insoluble
      complexes between pea protein isolate (PPI) and gum arabic (GA) mixtures as a
      function of pH (6.0-1.5), salt concentration (NaCl, 0-50 mM), and protein
      polysaccharide weight mixing ratio (1:4 to 10:1 w/w). For mixtures in the absence
      of salt and at a 1:1 mixing ratio, two structure-forming transitions were
      observed as a function of pH. The first event occurred at a pH of 4.2, with the
      second at pH 3.7, indicating the formation of soluble and insoluble complexes,
      respectively. Sodium chloride (<or=7.5 mM) was found to have no effect on
      biopolymer interactions, but interfered with interactions at higher levels (>7.5
      mM) due to substantial PPI aggregation. The pH at which maximum PPI-GA
      interactions occurred was 3.5 and was independent of NaCl levels. As PPI-GA
      ratios increased, structure-forming transitions shifted to higher pH.

PMID- 19170636
TI  - Levels of bisphenol A in canned soft drink products in Canadian markets.
AB  - The method developed previously for the determination of bisphenol A (BPA) in
      liquid infant formula was adapted and validated for determination of BPA in soft
      drink products. This method was based on solid phase extraction and
      derivatization with acetic anhydride followed by gas chromatography-mass
      spectrometry in selected-ion monitoring mode. The average method detection limit
      was 0.045 microg/L for a 10 mL sample. The average extraction recoveries were 101
      and 99.9% obtained with seven different soft drink products spiked with BPA at
      0.5 and 2.5 microg/L, respectively. Good repeatability of the method was observed
      with replicate analyses of seven different soft drinks; relative standard
      deviations ranged from 1.3 to 6.6%. This method was used to analyze samples of 72
      canned soft drink products for BPA. Except for three products from which BPA-d16
      could not be recovered at all due to interference of product compositions (e.g.,
      quinine hydrochloride in tonic water), BPA was detected in samples of all the
      other products at levels ranging from 0.032 to 4.5 microg/L. About 75% of the
      products had BPA levels of <0.5 microg/L, and 85% of the products had BPA levels
      of <1 microg/L. Exposure to BPA through consumption of canned soft drink products
      is low; dietary intake of BPA was estimated at 0.027 microg/kg of body weight/day
      on the basis of the consumption of one canned soft drink with the highest BPA
      level (4.5 microg/L) for an adult with a 60 kg body weight, well below the
      provisional tolerable daily intake of 25 microg/kg of body weight/day established
      by Health Canada.

PMID- 19170637
TI  - Herbicidal activity of glucosinolate degradation products in fermented meadowfoam
      ( Limnanthes alba ) seed meal.
AB  - Meadowfoam ( Limnanthes alba ) is an oilseed crop grown in western Oregon. After
      extraction of the oil from the seeds, the remaining seed meal contains 2-4% of
      the glucosinolate glucolimnanthin. This study investigated the effect of
      fermentation of seed meal on its chemical composition and the effect of the
      altered composition on downy brome ( Bromus tectorum ) coleoptile emergence.
      Incubation of enzyme-inactive seed meal with enzyme-active seeds (1% by weight)
      resulted in complete degradation of glucolimnanthin and formation of 3
      methoxybenzyl isothiocyanate in 28% yield. Fermentation in the presence of an
      aqueous solution of FeSO(4) (10 mM) resulted in the formation of 3
      methoxyphenylacetonitrile and 2-(3-methoxyphenyl)ethanethioamide, a novel natural
      product. The formation of the isothiocyanate, the nitrile, and the thioamide, as
      a total, correlated with an increase of herbicidal potency of the seed meal (r(2)
      = 0.96). The results of this study open new possibilities for the refinement of
      glucosinolate-containing seed meals for use as bioherbicides.

PMID- 19170638
TI  - Effect of drying methods with the application of vacuum microwaves on the
      bioactive compounds, color, and antioxidant activity of strawberry fruits.
AB  - The objective of this study was to evaluate the application of vacuum-microwave
      drying (240, 360, and 480 W) in the production process of dehydrated strawberry
      and to compare and contrast the quality of these dehydrated strawberries in terms
      of their polyphenol compounds, concentration of some heat liable components, and
      color to that of freeze-dried, convective, and vacuum-dried strawberry. Thus, the
      effect of vacuum-microwave drying and other drying methods on the antioxidant
      activity of berries was evaluated. Whole fresh and dried fruits were assessed for
      phenolics (anthocyanins, flavanols, hydroxycinnamic acids, and flavonols),
      ascorbic acid, and antioxidant activity (all parameters were calculated on a dry
      matter basis). Analysis of data shows that ellagic acid and flavanol changes were
      affected by drying techniques and cultivar. Drying destroyed anthocyanins,
      flavanols, and ascorbic acid, and there was a significant decrease in antioxidant
      activity. The most striking result was that conventional and vacuum drying
      decreased antioxidant activity in both cultivars, whereas contradictory results
      were found for vacuum-microwave processed strawberry. This study has demonstrated
      that vacuum-microwave drying, especially at 240 W, can produce high-quality
      products, with the additional advantage of reduced processing times, compared to
      other processes such as freeze-drying.

PMID- 19170639
TI  - Binding thermodynamics of the N-terminal peptide of the CCR5 coreceptor to HIV-1
      envelope glycoprotein gp120.
AB  - The initial events of HIV-1 cell infection involve the sequential binding of the
      viral envelope glycoprotein gp120 to the cellular CD4 receptor and the
      coreceptor, usually CCR5 or CXCR4. Binding to the coreceptor triggers the chain
      of events that culminates with the entry of the virus into the cell. In this
      process, the interaction of gp120 with the tyrosine-sulfated N-terminus of CCR5
      is critical; however, this interaction has never been characterized at a
      quantitative or thermodynamic level. Here, we present the first thermodynamic
      analysis of the interaction of gp120 with the N-terminal peptide of the CCR5
      coreceptor. Microcalorimetric titrations demonstrate that measurable binding of
      S22 peptide, a 22-amino acid tyrosine-sulfated peptide corresponding to the CCR5
      N-terminus, requires prior binding of CD4 to gp120. The S22 peptide binds to the
      gp120-CD4 complex with a binding affinity of 4.5 x 10(5) M(-1) (K(d) = 2.2
      microM) in an enthalpically and entropically favorable process. An identical
      peptide lacking the sulfated tyrosine residues is unable to bind the gp120-CD4
      complex. These results indicate that the sulfated tyrosines contribute close to 
      3.5 kcal/mol to the Gibbs energy of binding. Furthermore, the S22 peptide is a
      competitive inhibitor of the 17b HIV-1 neutralizing antibody, which is known to
      bind to the CCR5 coreceptor site in gp120. Together, these results point toward
      compounds containing sulfated aromatic groups as potential inhibitors of viral
      entry. In analogy to existing inhibitors that bind to the CCR5 coreceptor
      directly, these compounds will accomplish the same result by binding to the
      coreceptor site in gp120.

PMID- 19170640
TI  - Molecular organization of cylindrical sexithiophene aggregates measured by X-ray
      scattering and magnetic alignment.
AB  - We have determined the internal organization of elongated sexithiophene
      aggregates in solution by combining small-angle X-ray scattering and magnetic
      birefringence experiments. The different aggregate axes can be probed
      independently by performing the experiments on magnetically aligned aggregates.
      We have found multiwalled cylindrical aggregates consisting of radially oriented
      sexithiophene molecules with pi-pi-stacking in the tangential direction, a
      structure that is considerably different from those previously found in other
      solvents. The aggregate morphology of this semiconducting material can thus be
      tuned by using different solvents, which offers the attractive perspective to
      steer chemical self-assembly toward nanostructures with desired functionalities,
      especially in combination with the alignment in a magnetic field.

PMID- 19170641
TI  - The dewetting properties of lotus leaves.
AB  - The high dewetting abilities of lotus leaves can be transited to a complete
      wetting state by soaking the leaves in water at a depth of 50 cm for 2 h.
      However, after being dried by N2 gas, the high dewetting behavior of lotus leaves
      may be mostly restored. This indicates that experimental procedure might
      considerably affect the dewetting abilities of lotus leaves. To discover the
      mechanism underlying this interesting dewetting phenomena, the dewetting force
      was used to characterize the dewetting abilities of surfaces, and model studies
      to mimic the papillae were done. Surface hydrophobicity, sizes, rise angles, and
      secondary structures of the models' sides affected their dewetting force with
      water. So we suggested that the dewetting states, Cassie or Wenzel's state, of
      lotus surfaces depend much on the depth of water, i.e., the hydraulic pressure.
      On the other hand, the primary structures of papillae in Cassie's state led to a
      high receding angle with respect to the plane of the leaf during the dewetting
      measurement. The secondary structures and micro/nano arrays of papillae increased
      the dewetting abilities of lotus leaves, since no water intruded between
      papillae. However, the structures of papillae in Wenzle's state significantly
      reduced the dewetting abilities of lotus leaves after being soaked at a depth of
      50 cm for 2 h. Therefore, as for novel designs of microdevices floating on water,
      including the use of the high dewetting properties of suphydrophobic materials,
      surface (primary or secondary) microstructure and external pressure, such as
      static hydraulic pressure, must be taken into account.

PMID- 19170642
TI  - Anisotropy in hydrogen-passivated and organically modified nanoporous silicon
      surfaces studied by polarization dependent IR spectroscopy.
AB  - Infrared spectroscopic ellipsometry (IRSE) was applied for characterization of
      porous silicon (PSi) electrochemically prepared in acidic fluoride solution. When
      no formation of SiO2 was involved in the preparation, an anisotropic distribution
      of PSi bonds with the terminating molecules was achieved. On the contrary,
      oxidation of PSi samples during the preparation led to an isotropic structure. IR
      spectra obtained from organically functionalized PSi surfaces suggested that the
      morphology of the organic layer on PSi was anisotropic for electrochemical
      grafting of methyl but not nitrobenzene. Comparison between the IRSE spectra
      obtained from PSi and Si(111) surfaces and application of optical models
      supported these observations.

PMID- 19170643
TI  - Surface adsorption isotherms and surface excess densities of n-butane in
      silicalite-1.
AB  - We present isotherms for the adsorption of n-butane on the external and internal
      surfaces of silicalite, in the temperature range of 320-400 K and at pressures up
      to 530 kPa. The isotherms were calculated using molecular dynamics simulations. A
      modified thermostatting algorithm, Soft-HEX, was developed for this purpose. The
      results for the external as well as the internal surface were fitted to Langmuir
      models, and equilibrium constants are reported. Two surface structures were
      considered: a flat surface having only one adsorption site and a surface with a
      zigzag texture, characterized by two adsorption sites. The surface excess
      concentrations were computed. Negative surface excesses were found in some cases,
      indicating that the surface can serve as a barrier to transport. We show that
      Henry's law can be used to calculate adsorbate concentration-gas pressure
      relationships, and that the surface can be regarded as a thermodynamic system.
      These findings are important for studies of the surfaces as barriers to
      transport.

PMID- 19170644
TI  - Linear assembly of Au nanorods using biomimetic ligands.
AB  - The main goal of self-assembly processes is to arrange nanomaterials in specific
      orientations to produce designer three-dimensional architectures. These
      structures are produced in response to desired target systems where a specific
      arrangement of materials is required for structural, electronic, or optical
      applications. The level of complexity attained using present materials-based
      processes is relatively low, while highly complex structures are regularly
      produced in nature through processes developed after millennia of evolution. By
      modeling biomimetic processes with current materials designs, production of
      highly structured and three-dimensionally assembled materials is possible. Simple
      amino acids represent starting biobased systems to study the biomimetic assembly
      of nanomaterials in solution. Here we present evidence demonstrating that the
      assembly of Au nanorods into linear structures using the amino acid cysteine is
      controlled by both thiol and amine attachment to the tips of adjacent nanorods.
      This structural motif was isolated by studying the assembly process using
      cysteine and its biomimetic homologues 3-mercaptopropionic acid and cysteamine at
      a variety of solution pH values and ionic strengths. Understanding the
      fundamental mechanism of assembly for small biological molecules may prove useful
      in the development of assemblies based upon larger species such as peptides and
      proteins.

PMID- 19170645
TI  - Hydrolytic activity of free and immobilized cellulase.
AB  - Cellulase is an enzymatic complex which synergically promotes the degradation of
      cellulose to glucose. The adsorption behavior of cellulase from Trichoderma
      reesei onto Si wafers or amino-terminated surfaces was investigated by means of
      ellipsometry and atomic force microscopy (AFM) as a function of temperature. Upon
      increasing temperature from (24 +/- 1) to (60 +/- 1) degrees C, adsorption of
      cellulase became faster and more pronounced and the mean roughness of cellulase
      adsorbed layers increased. In the case of cellulase adsorbed onto Si wafers,
      Arrhenius's plot allowed us to estimate the adsorption energy as 24.2 kJ mol(-1).
      The hydrolytic activity of free cellulase and cellulase immobilized onto Si
      wafers was tested using cellulose dispersions as substrates. The incubation
      temperature ranged from (37 +/- 1) to (60 +/- 1) degrees C. The highest
      efficiency was observed at (60 +/- 1) degrees C. The amount of glucose produced
      by free cellulase was approximately 20% higher than that obtained from
      immobilized cellulase. However, immobilizing cellulase onto Si wafers proved to
      be advantageous because they could be reused six times while retaining their
      original activity level. Such an effect was attributed to surface hydration,
      which prevents enzyme denaturation. The hydrolytic activity of cellulase
      immobilized onto amino-terminated surfaces was slightly lower than that observed
      for cellulase adsorbed onto Si wafers, and reuse was not possible.

PMID- 19170646
TI  - Context-dependent adsorption behavior of cyclic and linear peptides on metal
      oxide surfaces.
AB  - Peptides with specific binding affinity to inorganic materials bridge biological
      systems with synthetic inorganic materials. Many inorganic-binding peptides were
      isolated using combinatorial peptide libraries without a good understanding of
      the interaction mechanism, which thus hinders the practical application of these
      peptides. Besides the amino acid composition, peptides' structure (e.g., cyclic
      structure constrained by disulfide bond) is believed to play an important role in
      their binding behavior. A cyclic peptide STB1 (-CHKKPSKSC-) was previously
      identified to electrostatically bind to TiO2 and SiO2. In the present study, the
      binding behavior (affinity and conformation) of STB1 and its linear version LSTB1
      (-AHKKPSKSA-) on a TiO2 or SiO2 surface was investigated in three different
      contexts (i.e., free peptides, phage particles displaying peptides, and LacI
      peptide fusion protein) using quartz crystal microbalance with energy dissipation
      measurement (QCM-D). The binding kinetics of STB1 and LSTB1 in the context of
      fusion protein to either metal oxide was quantitatively analyzed. LSTB1 showed
      similar binding behavior on both TiO2 and SiO2 surfaces. In the context of phage
      displayed and LacI-hosted peptides, STB1 was found to have weaker binding
      affinity than LSTB1 for either metal oxide, but it was able to distinguish
      between SiO2 and TiO2. This is probably because LSTB1 has a much more flexible
      structure than STB1, as shown by the molecular dynamics simulation. The
      structural flexibility of LSTB1 enables it to explore a wider range of
      conformations to maximize its interaction with TiO2 and SiO2.

PMID- 19170647
TI  - Solution properties of a thermosensitive triblock copolymer of N-alkyl
      substituted acrylamides.
AB  - An ABC triblock copolymer PnPA(124)-b-PiPA80-b-PEMA(44) was synthesized by a
      sequential three-step reversible addition-fragmentation chain transfer (RAFT)
      polymerization of N-n-propylacrylamide (nPA), N-isopropylacrylamide (iPA), and
      N,N-ethylmethylacrylamide (EMA). The thermoresponsive characteristics of the
      aqueous solution of the triblock copolymer have been studied in comparison with
      the corresponding mono- and diblocks by UV-visible and NMR spectroscopies,
      differential scanning calorimetry, and dynamic light scattering. The
      hydrophilicity of the blocks influences each other, rendering each block a phase
      transition temperature different from that of the corresponding homopolymers. The
      cloud points of the three steps of the phase separations were determined to be
      31.5, 46.8, and 57.6 degrees C for steps one to three, respectively, while
      heating the aqueous solution of the triblock copolymer. At approximately 31
      degrees C, the PnPA block started to dehydrate, causing the formation of micelles
      with the PnPA block as the core, dehydrated PiPA as the shell, and water-soluble
      PEMA block as the corona. The collapse of the dehydrated PiPA block was
      restricted by the shielding and stretching effect of the neighboring soluble PEMA
      block, and the resultant micelles had a high water content in their hydrodynamic
      volume. Continued increase in temperature to approximately 47 degrees C caused
      further dehydration of the micelles, and the final collapse of the third block of
      PEMA at approximately 58 degrees C led to further aggregation of the micelles.

PMID- 19170648
TI  - Nanoparticles, helical fibers, and nanoribbons of an achiral twin-tapered bi
      1,3,4-oxadiazole derivative with strong fluorescence.
AB  - A twin-tapered bi-1,3,4-oxadiazole derivative (BOXD-T8) showed a monomeric
      feature and intramolecular charge transition at concentrations lower than 10(-5)
      mol/L. BOXD-T8 molecules self-assembled to nanoparticles and further to helical
      nanofibers with blue fluorescence emission in DMSO, while nanoribbons resulted in
      an emission-enhanced gel in ethanol. The strong fluorescent emissions of BOXD-T8
      in an isolated state in apolar solvents were attributed to the coplanar
      conformation of the rigid backbone and the strong fluorescent emissions of BOXD
      T8 in the aggregation states were attributed to the coplanar conformation of the
      rigid backbone and J aggregation.

PMID- 19170649
TI  - Effect of confinement on the fluid properties of ammonia in mesopores of MCM-41
      and SBA-15.
AB  - The effect of pore size on capillary condensation and solid-liquid phase changes
      of ammonia in MCM-41 and SBA-15 was studied by adsorption and FTIR measurements
      of condensed phases at low temperatures. Adsorption isotherms are all typical
      type IV on the fully hydroxylated surfaces, without hysteresis loops in the
      smaller pores (d < 2.4 nm). In the larger pores, hysteresis loops appear at lower
      temperatures and disappear with increasing temperature, i.e., the capillary
      critical phenomenon was detected (hysteresis critical point). The criticality of
      the adsorption hysteresis loop is very similar to that for nonpolar nitrogen in
      mesopores of various shapes, suggesting that this is a universal phenomenon among
      fluids in mesopores. Freezing and melting of capillary-condensed ammonia were
      observed by FTIR spectroscopy. The melting temperature of capillary-condensed
      ammonia decreased with decreasing pore size, which is similar in the behavior of
      freezing. In the smaller pores (d < 2.4 nm); however, ammonia was not frozen. It
      is suggested that the capillary-condensed inner part, i.e., inside the ammonia
      monolayer, is affected too much by the pore wall and/or is too small in volume to
      crystallize. In the larger pores of SBA-15, crystallization is remarkably
      segregated from ammonia molecules strongly coordinated to surface hydroxyls.

PMID- 19170650
TI  - A new method to evaluate the surface dipole potential of thiol and disulfide self
      assembled monolayers and its application to a disulfidated tetraoxyethylene
      glycol.
AB  - A procedure to evaluate the surface dipole potential chi of thiol and disulfide
      self-assembled monolayers (SAMs) is described. The procedure consists of self
      assembling the monolayers on a hanging mercury drop electrode and of measuring
      the charge involved in a progressive expansion of the mercury drop. This
      measurement is then combined with an estimate of the charge density q experienced
      by diffuse layer ions, obtained by measuring the diffuse layer capacitance of the
      SAM at different electrolyte concentrations by electrochemical impedance
      spectroscopy. These chi measurements, combined with chronocoulometric
      measurements of the total charge density sigma(M) against potential, indicate
      that SAMs of tetraoxyethylene glycol-D,L-alpha-lipoic acid ester (TEGL), 2,3-di-O
      phytanyl-sn-glycerol-1-tetraoxyethylene glycol-D,L-alpha-lipoic ester (DPTL), and
      trioxyethyleneoxythiol (EO3) on mercury may undergo a reversal in the surface
      dipole potential of their polyoxyethylene chain with a change in the interfacial
      electric field. Moreover, TEGL and EO3 form stable SAMs without electron transfer
      to the metal, while no such conclusion can be drawn for DPTL.

PMID- 19170651
TI  - Determination of the zeta potential of porous substrates by droplet deflection.
      I. The influence of ionic strength and pH value of an aqueous electrolyte in
      contact with a borosilicate surface.
AB  - This paper presents a new method to determine the zeta potential of porous
      substrates in contact with a liquid. Electroosmosis, arising near the
      solid/liquid boundaries within a fully saturated porous substrate, pumps against
      the capillary pressure arising from the surface tension of a droplet placed in
      series with the pump. The method is based on measuring the liquid/gas interface
      deflection due to the imposed electric potential difference. The distinguishing
      features of our technique are accuracy, speed, and reliability, accomplished with
      a straightforward and cost-effective setup. In this particular setup, a bistable
      configuration of two opposing droplets is used. The energy barrier between the
      stable states defines the range of capillary resistance and can be tuned by the
      total droplet volume. The electroosmotic pump is placed between the droplets. The
      large surface area-to-volume ratio of the porous substrate enables the pumping
      strength to exceed the capillary resistance even for droplets small enough that
      their shapes are negligibly influenced by gravity. Using a relatively simple
      model for the flow within the porous substrate, the zeta potential resulting from
      the substrate-liquid combination is determined. Extensive measurements of a
      borosilicate substrate in contact with different aqueous electrolytes are made.
      The results of the measurements clarify the influence of the ionic strength and
      pH value on the zeta potential and yield an empirical relationship important to
      engineering approaches.

PMID- 19170652
TI  - Controlled aniline polymerization strategies for polyaniline micro- and nano self
      assembling into practical electronic devices.
AB  - Electroless polymerization of aniline on platinum is investigated for polyaniline
      micro- and nanostructuring into practical electronic devices. This type of
      reaction is adapted to estimate its usefulness in a lithographic process. For
      practical electronic device fabrication, electroless polymerization of aniline
      can be used to electrically bridge initially independent platinum electrodes. As
      this application requires a polyaniline bridge to form over a nonconductive
      material before an electrical contact is obtained, polyaniline growth using
      chemical oxidative reaction is investigated on substrates presenting surface
      tension contrast patterns.

PMID- 19170655
TI  - A strategy for the risk assessment of human genotoxic metabolites.
AB  - The role of metabolism in genotoxicity and carcinogenicity of many chemicals is
      well established. Accordingly, both in vitro metabolic activation systems and in
      vivo assays are routinely utilized for genotoxic hazard identification of drug
      candidates prior to clinical investigations. This should, in most cases provide a
      high degree of confidence that the genotoxic potential of the parent and
      associated metabolites have been characterized. However, it is well known that
      significant differences can exist between human metabolism and that which occurs
      with in vitro and in vivo genotoxicity tests. This poses challenges when
      considering the adequacy of hazard identification and cancer risk assessment if a
      human metabolite of genotoxic concern is identified during the course of drug
      development. Since such challenges are particularly problematic when recognized
      in the later stages of drug development, a framework for conducting a
      carcinogenic risk assessment for human genotoxic metabolites is desirable. Here,
      we propose a risk assessment method that is dependent upon the availability of
      quantitative human and rodent ADME (absorption, distribution, metabolism,
      excretion) data, such that exposures to a metabolite of genotoxic concern can be
      estimated at the intended human efficacious dose and the maximum dose used in the
      2-year rodent bioassay(s). The exposures are then applied to the risk assessment
      framework, based on known cancer potencies, that allows one to understand the
      probability of a known or suspect genotoxic metabolite posing a carcinogenic risk
      in excess of 1 in 100,000. Practical case examples are presented to illustrate
      the application of the risk assessment method within the context of drug
      development and to highlight its utility and limitations.

PMID- 19170656
TI  - Molecular analysis of heparan sulfate biosynthetic enzyme machinery and
      characterization of heparan sulfate structure in Nematostella vectensis.
AB  - HS (heparan sulfate) proteoglycans are key regulators of vital processes in the
      body. HS chains with distinct sequences bind to various protein ligands, such as
      growth factors and morphogens, and thereby function as important regulators of
      protein gradient formation and signal transduction. HS is synthesized through the
      concerted action of many different ER (endoplasmic reticulum) and Golgi-resident
      enzymes. In higher organisms, many of these enzymes occur in multiple isoforms
      that differ in substrate specificity and spatial and temporal expression. In
      order to investigate how the structural complexity of HS has evolved, in the
      present study we focused on the starlet sea anemone (Nematostella vectensis),
      which belongs to the Anthozoa, which are considered to have retained many
      ancestral features. Members of all of the enzyme families involved in the
      generation and modification of HS were identified in Nematostella. Our results
      show that the enzymes are highly conserved throughout evolution, but the number
      of isoforms varies. Furthermore, the HS polymerases [Ext (exostosin) enzymes
      Ext1, Ext2 and Ext-like3] represent distinct subgroups, indicating that these
      three genes have already been present in the last common ancestor of Cnidaria and
      Bilateria. In situ hybridization showed up-regulation of certain enzymes in
      specific areas of the embryo at different developmental stages. The specific mRNA
      expression pattern of particular HS enzymes implies that they may play a specific
      role in HS modifications during larval development. Finally, biochemical analysis
      of Nematostella HS demonstrates that the sea anemone synthesizes a polysaccharide
      with a unique structure.

PMID- 19170657
TI  - Lipid rafts enriched in phosphatidylglucoside direct astroglial differentiation
      by regulating tyrosine kinase activity of epidermal growth factor receptors.
AB  - Membrane lipid rafts provide a specialized microenvironment enriched with
      sphingolipids and phospholipids containing saturated fatty acids and serve as a
      platform for various intracellular signalling pathways. PtdGlc
      (phosphatidylglucoside) is a type of glycophospholipid localized in the outer
      leaflet of the plasma membrane. Owing to PtdGlc's unique fatty acid composition,
      exclusively composed of C(18:0) at sn-1 and C(20:0) at sn-2 of the glycerol
      backbone, it tends to form PGLRs (PtdGlc-enriched lipid rafts). Previously, we
      demonstrated that PGLRs reside on the cell surface of astroglial cells from fetal
      rat brain [Nagatsuka, Horibata, Yamazaki, Kinoshita, Shinoda, Hashikawa, Koshino,
      Nakamura and Hirabayashi (2006) Biochemistry 45, 8742-8750]. In the present
      study, we observed PGLRs in astroglial lineage cells at mid-embryonic to early
      postnatal stages of developing mouse cortex. This suggests that PGLRs are
      developmentally correlated with astroglial differentiation during fetal cortical
      development. Our cell culture studies with multipotent neural progenitor cells
      prepared from fetal mouse telencephalon demonstrated that treatment with EGF
      (epidermal growth factor) or anti-PtdGlc antibody caused recruitment of EGFRs
      (EGF receptors) into lipid raft compartments, leading to activation of EGFRs.
      Moreover, the activation of EGFRs by antibody triggered downstream tyrosine
      kinase signalling and induced marked GFAP (glial fibrillary acidic protein)
      expression via the JAK (Janus kinase)/STAT (signal transducer and activator of
      transcription) signalling pathway. These findings strongly suggest that PGLRs are
      physiologically coupled to activated EGFRs on neural progenitor cells during
      fetal cortical development, and thereby play a distinct role in mediating
      astrogliogenesis.

PMID- 19170658
TI  - N-terminal pro-B-type natriuretic peptide complements the GRACE risk score in
      predicting early and late mortality following acute coronary syndrome.
AB  - The GRACE (Global Registry of Acute Coronary Events) risk score has been shown to
      offer predictive power with regard to death and AMI (acute myocardial infarction)
      in patients with ACS (acute coronary syndromes). NT-proBNP (N-terminal pro-B-type
      natriuretic peptide) has also been found to be useful in predicting mortality
      following ACS. In the present study, we sought to investigate the use of the
      GRACE score and NT-proBNP levels at predicting risk of early and late deaths
      following ACS. We studied 1033 patients (740 men, mean age 66.5+/-12.7 years)
      with AMI. Blood was drawn once within 24 h following the onset of chest pain. The
      plasma concentration of NT-proBNP was determined using an in-house non
      competitive immunoassay. Patients were GRACE risk scored. The 30-day mortality
      was 3.7% and the 6-month mortality was 7.8%, and all were related to higher GRACE
      risk scores (P=0.001 for trend). Higher NT-proBNP levels were also related to
      increased mortality (P<0.0001). In a Cox proportional hazards model, independent
      predictors of 30-day and 6-month mortality included NT-proBNP levels and the
      GRACE risk score. The receiver-operating curve for the GRACE risk score was
      complemented by NT-proBNP levels for prediction of 30-day mortality [AUC (area
      under the curve), 0.85] and 6-month mortality (AUC, 0.81). NT-proBNP gives
      complementary information to the GRACE risk score for predicting early and late
      mortality. The inclusion of the NT-proBNP blood test is useful in risk
      stratifying patients after ACS.

PMID- 19170659
TI  - Neurodevelopmental outcome and pulmonary morbidity two years after early versus
      late surfactant treatment: does it really differ?
AB  - AIM: To investigate whether neurodevelopmental outcome or pulmonary morbidity at
      age two years might be different after early versus late surfactant treatment in
      intubated preterm infants with severe respiratory distress syndrome (RDS).
      METHODS: In 185 ex-preterm infants of 27-32 completed weeks of gestation, who
      were enrolled in a controlled trial of early versus late surfactant treatment (31
      +/- 19 min vs. 202 +/- 80 min, respectively), a standardized follow up of medical
      history, pulmonary morbidity and neurodevelopmental outcome using the Griffiths
      scales were carried out. RESULTS: Neurobehavioural and motor development was
      comparable in both groups, as was medical history and actual morbidity. However,
      in the early treatment group a delay in the subscale 'personal social' of the
      Griffiths test and in one 'milestone' of motor development (rolling over from
      supine to prone) was noticed, and the rate of increased muscular tone was
      significantly higher. CONCLUSION: In terms of long-term morbidity or neurological
      development there is no obvious advantage of an immediate surfactant
      administration after intubation in preterm infants with RDS. This is in line with
      our results published earlier on morbidity at discharge, so improvement of gas
      exchange after intubation can first be awaited before surfactant is indicated.

PMID- 19170660
TI  - Effect of proton pump inhibition on the gastric volume: assessed by magnetic
      resonance imaging.
AB  - BACKGROUND: Proton pump inhibitor (PPI) therapy is known to suppress gastric acid
      secretion. Thus PPI therapy may decrease gastric volume and gastric contents
      available for gastro-oesophageal reflux by decreasing acid secretion. AIM: To
      determine the effect of PPI therapy on the gastric volume after a standard meal.
      METHODS: A total of nine healthy subjects were studied using magnetic resonance
      imaging, before and after a standard liquid meal mixed with a paramagnetic
      contrast to help demarcate the gastric region. Images were acquired for a total
      of 90 min after the meal. Studies were conducted before and following
      esomeprazole twice daily for 7 days. Images were analysed to determine the
      gastric liquid volume. RESULTS: Gastric volume, 15 min after the meal peaked to
      611 +/- 37 mL on the control day and 539 +/- 30 mL following the PPI
      administration (P < 0.001). Average gastric volume remained significantly lower
      (56 +/- 9 mL, P < 0.05) on the PPI therapy from 5 to 75 min after the meal.
      CONCLUSIONS: Proton pump inhibitor therapy causes a significant reduction in the
      gastric contents volume during first 75 min after the meal. In addition to
      increasing the gastric pH, PPI therapy may decrease the frequency of gastro
      oesophageal reflux by decreasing the volume of gastric contents.

PMID- 19170661
TI  - Quantitative lipid metabolomic changes in alcoholic micropigs with fatty liver
      disease.
AB  - BACKGROUND: Chronic ethanol consumption coupled with folate deficiency leads to
      rapid liver fat accumulation and progression to alcoholic steatohepatitis (ASH).
      However, the specific effects of alcohol on key liver lipid metabolic pathways
      involved in fat accumulation are unknown. It is unclear whether lipid synthesis,
      lipid export, or a combination of both is contributing to hepatic steatosis in
      ASH. METHODS: In this study we estimated the flux of fatty acids (FA) through the
      stearoyl-CoA desaturase (SCD), phosphatidylethanolamine-N-methyltransferase
      (PEMT), and FA elongation pathways in relation to liver triacylglycerol (TG)
      content in Yucatan micropigs fed a 40% ethanol folate-deficient diet with or
      without supplementation with S-adenosyl methionine (SAM) compared with controls.
      Flux through the SCD and PEMT pathways was used to assess the contribution of
      lipid synthesis and lipid export respectively on the accumulation of fat in the
      liver. Liver FA composition within TG, cholesterol ester (CE),
      phosphatidylethanolamine, and phosphatidylcholine classes was quantified by gas
      chromatography. RESULTS: Alcoholic pigs had increased liver TG content relative
      to controls, accompanied by increased flux through the SCD pathway as indicated
      by increases in the ratios of 16:1n7 to 16:0 and 18:1n9 to 18:0. Conversely, flux
      through the elongation and PEMT pathways was suppressed by alcohol, as indicated
      by multiple metabolite ratios. SAM supplementation attenuated the TG accumulation
      associated with alcohol. CONCLUSIONS: These data provide an in vivo examination
      of liver lipid metabolic pathways confirming that both increased de novo
      lipogenesis (e.g., lipid synthesis) and altered phospholipid metabolism (e.g.,
      lipid export) contribute to the excessive accumulation of lipids in liver
      affected by ASH.

PMID- 19170663
TI  - Field and laboratory alcohol detection with 2 types of transdermal devices.
AB  - BACKGROUND: Two types of transdermal electrochemical sensors that detect alcohol
      at the skin surface were evaluated. One, the AMS SCRAM device, is locked onto the
      ankle and is based on a fuel cell sensor; the other, a Giner WrisTAS device, worn
      on the wrist, is based on a proton exchange membrane. SCRAM is used by several
      court systems in the United States to monitor alcohol offenders, WrisTAS, a
      research prototype, is not commercially available. METHODS: The 2 devices were
      worn concurrently by 22 paid research subjects (15 men, 7 women), for a combined
      total of 96 weeks. Subjects participated in both laboratory-dosed drinking to a
      target of 0.08 g/dl blood alcohol concentration (BAC), and normal drinking on
      their own; all subjects were trained to use and carry a portable fuel-cell breath
      tester for BAC determinations. Overall 271 drinking episodes with BAC > or = 0.02
      g/dl formed the signal for detection-60 from laboratory dosing, and 211 from self
      dosed drinking, with BAC ranging from 0.02 to 0.230 g/dl (mean 0.077 g/dl).
      RESULTS: False negatives were defined as a transdermal alcohol concentration
      response equivalent <0.02 g/dl when BAC > or = 0.02 g/dl. The overall true
      positive hit rate detected by WrisTAS was 24%. The low detection rate was due to
      erratic output and not recording during nearly 67% of all episodes; reportedly a
      chipset, not a sensor problem. SCRAM correctly detected 57% across all BAC
      events, with another 22% (total 79%) detected, but as <0.02 g/dl. When subjects
      dosed themselves to BAC > or = 0.08 g/dl, SCRAM correctly detected 88% of these
      events. SCRAM devices lost accuracy over time likely due to water accumulation in
      the sensor housing. Neither unit had false-positive problems when true BAC was
      <0.02 g/dl. CONCLUSIONS: Each device had peculiarities that reduced performance,
      but both types are able to detect alcohol at the skin surface. With product
      improvements, transdermal sensing may become a valuable way to monitor the
      alcohol consumption of those who should be abstaining.

PMID- 19170662
TI  - Altered impulse control in alcohol dependence: neural measures of stop signal
      performance.
AB  - BACKGROUND: Altered impulse control has been implicated in the shaping of
      habitual alcohol use and eventual alcohol dependence. We sought to identify the
      neural correlates of altered impulse control in 24 abstinent patients with
      alcohol dependence (PAD), as compared to 24 demographics matched healthy control
      subjects (HC). In particular, we examined the processes of risk taking and
      cognitive control as the neural endophenotypes of alcohol dependence. METHODS: To
      this end, functional magnetic resonance imaging (fMRI) was conducted during a
      stop signal task (SST), in which a procedure was used to elicit errors in the
      participants. The paradigm allowed trial-by-trial evaluation of response
      inhibition, error processing, and post-error behavioral adjustment. Furthermore,
      by imposing on the subjects to be both fast and accurate, the SST also introduced
      a distinct element of risk, which participants may or may not avert during the
      task. Brain imaging data were analyzed with Statistical Parametric Mapping in
      covariance analyses accounting for group disparity in general performance.
      RESULTS: The results showed that, compared to HC, PAD demonstrated longer go
      trial reaction time (RT) and higher stop success rate (SS%). HC and PAD were
      indistinguishable in stop signal reaction time (SSRT) and post-error slowing
      (PES). In a covariance analysis accounting for go trial RT and SS%, HC showed
      greater activity in the left dorsolateral prefrontal cortex than PAD, when
      subjects with short and long SSRT were contrasted. By comparing PAD and HC
      directly during stop errors (SE), as contrasted with SS, we observed greater
      activity in PAD in bilateral visual and frontal cortices. Compared to HC, PAD
      showed less activation of the right dorsolateral prefrontal cortex during PES, an
      index of post-error behavioral adjustment. Furthermore, PAD who showed higher
      alcohol urge at the time of the fMRI were particularly impaired in dorsolateral
      prefrontal activation, as compared to those with lower alcohol urge. Finally,
      compared to HC subjects, PAD showed less activity in cortical and subcortical
      structures including putamen, insula, and amygdala during risk-taking decisions
      in the SST. CONCLUSION: These preliminary results provided evidence for altered
      neural processing during impulse control in PAD. These findings may provide a
      useful neural signature in the evaluation of treatment outcomes and development
      of novel pharmacotherapy for alcohol dependence.

PMID- 19170665
TI  - Chronic ethanol feeding alters hepatocyte memory which is not altered by acute
      feeding.
AB  - BACKGROUND: Gene expression changes in the liver after acute binge drinking may
      differ from the changes seen in chronic ethanol feeding in the rat. The changes
      in gene expression after chronic ethanol feeding may sensitize the liver to
      alcohol-induced liver damage, which is not seen after acute binge drinking.
      METHODS: To test this hypothesis, gene microarray analysis was performed on the
      livers of rats (n = 3) fed an acute binge dose of ethanol (6 g/kg body wt) and
      killed at 3 and 12 hours after ethanol by gavage. The gene microarrays were
      compared with those made on the liver of rats from a previous study, in which the
      rats were fed ethanol by intragastric tube for 1 month (36% of calories derived
      from ethanol). RESULTS: Microarray analysis data varied between the acute and
      chronic models in several important respects. Growth factors increased mainly in
      the chronic alcohol fed rat. Changes in enzymes involved in oxidative stress were
      noted only with chronic ethanol feeding. Gene expression of fat metabolism was
      increased only with chronic ethanol feeding. Most importantly, epigenetic related
      enzymes and acetylation and methylation of histones changed only after chronic
      ethanol feeding. CONCLUSIONS: The results support the concept that chronic
      ethanol ingestion induces altered gene expression as a result of changes in
      epigenetic mechanisms, where acetylation and methylation of histones were
      altered.

PMID- 19170664
TI  - Association between Val66Met brain-derived neurotrophic factor (BDNF) gene
      polymorphism and post-treatment relapse in alcohol dependence.
AB  - BACKGROUND: The purpose of this study was to examine relationships between
      genetic markers of central serotonin (5-HT) and dopamine function, and risk for
      post-treatment relapse, in a sample of alcohol-dependent patients. METHODS: The
      study included 154 patients from addiction treatment programs in Poland, who met
      DSM-IV criteria for alcohol dependence. After assessing demographics, severity of
      alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of
      alcohol use at baseline, patients were followed for approximately 1 year to
      evaluate treatment outcomes. Genetic polymorphisms in several genes (TPH2,
      SLC6A4, HTR1A, HTR2A, COMT, and BDNF) were tested as predictors of relapse
      (defined as any drinking during follow-up) while controlling for baseline
      measures. RESULTS: Of 154 eligible patients, 123 (80%) completed follow-up and
      48% (n = 59) of these individuals relapsed. Patients with the Val allele in the
      Val66Met BDNF polymorphism and the Met allele in the Val158Met COMT polymorphism
      were more likely to relapse. Only the BDNF Val/Val genotype predicted post
      treatment relapse [odds ratio (OR) = 2.62; p = 0.019], and time to relapse (OR =
      2.57; p = 0.002), after adjusting for baseline measures and other significant
      genetic markers. When the analysis was restricted to patients with a family
      history of alcohol dependence (n = 73), the associations between the BDNF Val/Val
      genotype and relapse (OR = 5.76, p = 0.0045) and time to relapse (hazard ratio =
      4.93, p = 0.001) were even stronger. CONCLUSIONS: The Val66Met BDNF gene
      polymorphism was associated with a higher risk and earlier occurrence of relapse
      among patients treated for alcohol dependence. The study suggests a relationship
      between genetic markers and treatment outcomes in alcohol dependence. Because a
      large number of statistical tests were conducted for this study and the
      literature on genetics and relapse is so novel, the results should be considered
      as hypothesis generating and need to be replicated in independent studies.

PMID- 19170667
TI  - Point-wise estimation of non-linear effects of airborne pollen levels on asthma
      emergency room admissions.

PMID- 19170666
TI  - Searching for responders to acamprosate and naltrexone in alcoholism treatment:
      rationale and design of the PREDICT study.
AB  - BACKGROUND: Alcoholism represents a major public health issue and treating
      alcohol dependent patients remains an imminent challenge. Evidence based
      psychotherapies and pharmacotherapies are available. However, when administered
      to heterogeneous populations of patients effect sizes are only modest. We present
      the rationale and design of a double-blind randomized trial comparing
      acamprosate, naltrexone, and placebo. Additionally we subtype patients on the
      basis of biological and psychometric measures and explore their treatment
      response to both acamprosate and naltrexone. According to our initial hypothesis,
      the "relief drinker/craver" is an endophenotype associated with glutamatergic
      dysfunction who responds to acamprosate. The "reward drinker/craver" is mainly
      associated with alterations in the dopaminergic and opioidergic system and
      responds to naltrexone. METHODS: The study is planned for 430 patients (2:2:1 for
      both drugs and placebo) over 12 weeks of medication. All receive manualized
      counselling to improve compliance (Medical Management) which is extended to 6
      months. Subtyping is primarily done using the acoustic startle reflex, functional
      magnetic resonance imaging, positron emission tomography (in a subset of
      patients), and the Inventory of Drinking Situations. Relapsers will be re
      randomized into a second study where additional psychotherapy (Cognitive
      Behavioral Intervention) is used in a stepped care approach. Genotyping and
      additional analyses such as health economy are being done as well. The study
      follows the assessment methods, treatments, and medications used in the U.S.
      based COMBINE study, which will allow for a direct comparison between this U.S.
      study trial and a study performed in Europe.

PMID- 19170668
TI  - Selective allergy to Venus antiqua clam.

PMID- 19170669
TI  - The importance of nasal provocation test in the diagnosis of natural rubber latex
      allergy.
AB  - BACKGROUND: Most studies regarding natural rubber latex (NRL) allergy have
      concentrated on the prevalence using skin prick test (SPT) and specific IgE
      assay. The objective of this study is to examine the target organ (skin, nasal
      mucosa) responses in patients with positive SPT to NRL using the nasal
      provocation test (NPT) and glove use test (GUT). METHODS: Four thousand four
      hundred and twenty patients presented to our polyclinic between July 2003 and
      January 2007 were evaluated. One thousand six hundred and ninety-nine patients
      had positive SPT to one or more allergens (NRL and other inhaler allergens).
      Twenty-nine patients with positive SPT to NRL comprised the NRL sensitive group
      (group 1). Thirty-five randomized patients with positive SPT to an inhaler
      allergen other than NRL and negative NRL-specific IgE comprised atopic control
      group (group 2). Thirty healthy individuals who had no allergic diseases and had
      negative SPT and NRL-specific IgE comprised the healthy control group (group 3).
      RESULTS: The lowest NRL allergen concentration leading to NPT positiveness was
      0.05 microg/mL. NPT was negative in groups 2 and 3. NPT was found to have a
      sensitivity of 96%, specificity of 100%, negative predictive value of 98% and
      positive predictive value of 100%. GUT was found to have a sensitivity of 81%,
      specificity of 90%, negative predictive value of 75% and positive predictive
      value of 93%. CONCLUSIONS: Nasal provocation test was successfully used for the
      first time in the diagnosis of NRL allergy. NPT is a more sensitive method as
      compared to GUT.

PMID- 19170670
TI  - Differential expression of the interleukin 5 receptor alpha isoforms in blood and
      tissue eosinophils of nasal polyp patients.
AB  - BACKGROUND: Given the key role of interleukin-5 (IL-5) in eosinophil function, we
      investigated the regulated expression of the membrane-anchored (TM-IL-5Ralpha)
      isoform, or a secreted (SOL IL-5Ralpha) isoform, on both protein and transcript
      level in vitro and in vivo. METHODS: A real-time PCR, FACS and ELISA were
      established to determine IL-5Ralpha isoform expression in peripheral blood and
      nasal tissue from control subjects and nasal polyp (NP) patients with or without
      asthma. Human peripheral blood eosinophils were incubated with IL-5 and were
      analyzed for SOL-IL-5Ralpha and TM-IL-5Ralpha mRNA and protein levels in
      comparison with CD-69 expression. RESULTS: SOL-IL-5Ralpha and TM-IL-5Ralpha mRNA
      and protein expression was significantly increased in NP vs controls. In polyp
      tissue, SOL-IL-5Ralpha expression correlated to disease severity and eosinophils
      counts, whereas TM-IL-5Ralpha levels were inversely correlated to eosinophils
      counts and SOL-IL-5Ralpha expression. FACS analysis revealed increased CD-69 and
      decreased TM-IL-5Ralpha expression in NP tissue eosinophils vs blood eosinophils.
      Incubation of blood eosinophils with IL-5 caused up-regulation of CD-69 and down
      regulation of TM-IL-5Ralpha after 2 and 24 h. CONCLUSION: The expression of SOL
      IL-5Ralpha and TM-IL-5Ralpha differs according to the eosinophil activation state
      and localization in the body (blood vs tissue) and may therefore be involved in
      the fine-tuning of the eosinophil homeostasis. Exposure of eosinophils to IL-5
      reduces their responsiveness to IL-5 by regulated expression of the IL-5Ralpha
      isoforms. Since, TM-IL-5Ralpha is down-regulated and SOL-IL-5Ralpha
      (antagonistic) is upregulated in NP tissue, our findings are important to
      understand the clinical trials with anti-IL-5 in humans.

PMID- 19170671
TI  - Maternal smoking increases risk of allergic sensitization and wheezing only in
      children with allergic predisposition: longitudinal analysis from birth to 10
      years.
AB  - BACKGROUND: The role of passive smoking for allergies and asthma in children
      above the age of 3 years remains unclear and possible interactive effects with
      parental allergies have not been formally evaluated in long-term studies. To
      examine the interaction of passive smoking and an allergic predisposition
      regarding allergic sensitization, allergic airway symptoms and respiratory
      infections during the first 10 years of life. METHODS: In a prospective
      multicenter birth cohort study with 1314 recruited children in Germany, we
      assessed serum immunoglobulin E against common allergens at seven time points,
      and parental smoking and respiratory symptoms annually by using questionnaires.
      Longitudinal analyses were performed using generalized estimating equation models
      (stratified by parental allergy status). RESULTS: During the first 10 years, 18%
      of the children were exposed to regular maternal smoking since pregnancy, 43% to
      irregular maternal or only paternal smoking. Among children with two allergic
      parents, a mother who smoked regularly significantly increased the odds for
      allergic sensitization (adjusted OR 4.8, 95% CI 1.3-18.2) and wheezing (adjusted
      OR 5.7, 95% CI 1.7-19.0) in her child compared with children who were never
      exposed. For those with only one allergic parent, the odds were doubled and also
      statistically significant, whereas in children without allergic parents maternal
      smoking had no effects. There was no association of maternal smoking with
      allergic rhinitis or respiratory infections. CONCLUSIONS: Our results suggest
      that regular maternal smoking is a strong risk factor for allergic sensitization
      and asthma symptoms during the first 10 years of life, but only in children with
      allergic parents.

PMID- 19170672
TI  - Immunologic characterization of isoforms of Car b 1 and Que a 1, the major
      hornbeam and oak pollen allergens.
AB  - BACKGROUND: Birch pollen allergy is one of the most common causes of spring
      pollinosis often associated with hypersensitivity reactions to pollen of other
      Fagales species. Yet, only the major disease eliciting allergens of alder and
      hazel have been fully characterized. Therefore, the aim of this study was to
      perform cloning, expression and immunologic characterization of the Bet v 1
      homologues from oak (Que a 1) and hornbeam (Car b 1). METHODS: The isoform
      pattern of Car b 1 and Que a 1 was analyzed by proteomics using 2D gel
      electrophoresis and LC ESI-QTOF MS. Isoallergens showing high IgE-binding were
      cloned and expressed in Escherichia coli. IgE-binding activity of the recombinant
      proteins was determined by enzyme-linked immunosorbent assay (ELISA) and basophil
      mediator release assays using serum samples from patients mainly exposed either
      to oak and hornbeam or to birch pollen. Cross-reactivity of the allergens was
      further investigated at the T-cell level. RESULTS: Dominant isoforms of Car b 1
      and Que a 1, identified by mass spectrometry, showed different IgE-binding
      properties when testing Fagales pollen-allergic patients living in birch-free
      areas as compared to birch-sensitized individuals. CONCLUSION: Tree pollen
      allergic patients who are primarily exposed to Fagales pollen other than birch
      reacted stronger with rCar b 1 and rQue a 1 than with rBet v 1, as determined by
      inhibition ELISA and basophil mediator release assays. Thus, rCar b 1 and rQue a
      1 allergens should be considered for improving molecule-based diagnosis and
      therapy of tree pollen allergies manifesting in birch-free areas.

PMID- 19170673
TI  - Analysis of mitochondrial DNA diversity in Burkina Faso populations confirms the
      maternal genetic homogeneity of the West African goat.
AB  - To date, no comprehensive study has been performed on mitochondrial genetic
      diversity of the West African goat. Here, we analysed a 481-bp fragment of the
      HVI region of 111 goats representing four native West African populations, namely
      the three main Burkina Faso breeds, zoo-farm kept Dwarf goats and endangered
      Spanish goat breeds used as the outgroup. Analyses gave 83 different haplotypes
      with 102 variable sites. Most haplotypes (65) were unique. Only three haplotypes
      were shared between populations. Haplotypes were assigned to cluster A except for
      H45 (belonging to the Spanish Bermeya goat) which was assigned to cluster C.
      amova analysis showed that divergence between groups (Phi(CT)) was not
      statistically significant regardless of whether the partition in two hierarchical
      levels that was fitted included Spanish samples or not. The West African goat
      scenario shown here is consistent with that previously reported for the species:
      haplogroup A is predominant and has a very high haplotype diversity regardless of
      the geographic area or sampled breed. The large phenotypic differences observable
      between the West African Dwarf and Sahelian long-legged goat populations are not
      detectable with mitochondrial markers. Moreover, a previously suggested
      introgression of Sahelian goat southwards because of desertification could not be
      assessed using mtDNA information.

PMID- 19170674
TI  - Porcine skeletal muscle differentially expressed gene CMYA1: isolation,
      characterization, mapping, expression and association analysis with carcass
      traits.
AB  - To investigate the differences in gene expression between some obese and lean pig
      breeds, differential display of mRNA was employed in our previous research. One
      differentially expressed EST (BI596262) was further identified as the porcine
      cardiomyopathy associated 1 (CMYA1) gene because of its homology to the human
      CMYA1 gene. The full-length DNA of the porcine CMYA1 gene encompasses 9379 bp,
      including a complete open reading frame encoding 1839 amino acid residues, a 158
      bp 5'-untranslated region and a 630-bp 3'-untranslated region. The porcine CMYA1
      gene was assigned to chromosome 13 by the radiation hybrid panel (IMpRH). The
      porcine CMYA1 gene was expressed only in the striated muscle. Single nucleotide
      polymorphism (SNP) scanning in the coding region identified one synonymous
      mutation (c.1053C>T) and three missense mutations, c.1394A>G (p.His465Arg),
      c.1751A>G (p.Asp582Gly) and c.3290C>A (p.Thr1097Asp). The allele frequencies were
      tested among about 200 unrelated pigs from several pig breeds. Linkage mapping
      was further conducted with the SNP c.1751A>G (p.Asp582Gly) in a Berkshire x
      Yorkshire resource family and this confirmed that porcine CMYA1 is closely linked
      with Sw344 (distance = 2 cM, LOD score is 129.47), an interesting region
      harbouring a QTL for back fat thickness. Association analysis in our experimental
      pig population showed that different genotypes of CMYA1 gene were associated with
      different back fat thicknesses (P < 0.05). Our results suggest that the porcine
      CMYA1 gene has effects on porcine back fat deposition and further investigation
      will be necessary to illustrate the underlying mechanisms.

PMID- 19170675
TI  - Quantitative trait loci for performance traits in a broiler x layer cross.
AB  - An F(2) resource population, derived from a broiler x layer cross, was used to
      map quantitative trait loci (QTL) for body weights at days 1, 35 and 41, weight
      gain, feed intake, feed efficiency from 35 to 41 days and intestinal length. Up
      to 577 F(2) chickens were genotyped with 103 genetic markers covering 21 linkage
      groups. A preliminary QTL mapping report using this same population focused
      exclusively on GGA1. Regression methods were applied to line-cross and half-sib
      models for QTL interval mapping. Under the line-cross model, eight QTL were
      detected for body weight at 35 days (GGA2, 3 and 4), body weight at 41 days
      (GGA2, 3, 4 and 10) and intestine length (GGA4). Under the half-sib model, using
      sire as common parent, five QTL were detected for body weight at day 1 (GGA3 and
      18), body weight at 35 days (GGA2 and 3) and body weight at 41 days (GGA3). When
      dam was used as common parent, seven QTL were mapped for body weight at day 1
      (GGA2), body weight at day 35 (GGA2, 3 and 4) and body weight at day 41 (GGA2, 3
      and 4). Growth differences in chicken lines appear to be controlled by a
      chronological change in a limited number of chromosomal regions.

PMID- 19170676
TI  - An approach to canine behavioural genetics employing guide dogs for the blind.
AB  - The purpose of this study was to attempt to find related variables of the canine
      genome with behavioural traits of dogs maintained and tested in a guide dog
      facility which provided a relatively uniform environment. The study involved 81
      Labrador Retrievers that were being trained as guide dogs. Each dog was taken on
      walk-out sessions in which the trainer weekly recorded observations that were
      related to behavioural traits. The records were subjected to key-word analysis of
      14 behaviour-related words. A factor analysis on the appearance rate of the 14
      key words or phrases resulted in the extraction of six factors that accounted for
      67.4% of the variance. Factor 1, referred to as aggressiveness, was significantly
      related to the success or failure of the dog in qualifying as a guide dog, and
      was also related to the variable of litter identification. Factor 2, referred to
      as distraction, was related to the variable of trainer. Factor 3, activity level,
      was related to the variable of sex, and was significantly related to the
      polymorphisms of c.471T>C in the solute carrier family 1 (neuronal/epithelial
      high affinity glutamate transporter) member 2 gene and c.216G>A in the catechol-O
      methyltransferase gene. The involvement of polymorphisms c.471T>C and c.216G>A in
      behavioural patterns related to activity level is similar to comparable genetic
      studies in other mammalian species. These results contribute to a greater
      understanding of the role of these genes in behaviour.

PMID- 19170677
TI  - Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase
      III APEX trial in relapsed multiple myeloma: impact of a dose-modification
      guideline.
AB  - The frequency, characteristics and reversibility of bortezomib-associated
      peripheral neuropathy were evaluated in the phase III APEX (Assessment of
      Proteasome Inhibition for Extending Remissions) trial in patients with relapsed
      myeloma, and the impact of a dose-modification guideline on peripheral neuropathy
      severity and reversibility was assessed. Patients received bortezomib 1.3 mg/m(2)
      (days 1, 4, 8, 11, eight 21-d cycles, then days 1, 8, 15, 22, three 35-d cycles);
      bortezomib was held, dose-reduced or discontinued depending on peripheral
      neuropathy severity, according to a protocol-specified dose-modification
      guideline. Overall, 124/331 patients (37%) had treatment-emergent peripheral
      neuropathy, including 30 (9%) with grade >or=3; incidence and severity were not
      affected by age, number/type of prior therapies, baseline glycosylated
      haemoglobin level, or diabetes history. Grade >or=3 incidence appeared lower
      versus phase II trials (13%) that did not specifically provide dose-modification
      guidelines. Of patients with grade >or=2 peripheral neuropathy, 58/91 (64%)
      experienced improvement or resolution to baseline at a median of 110 d, including
      49/72 (68%) who had dose modification versus 9/19 (47%) who did not. Efficacy did
      not appear adversely affected by dose modification for grade >or=2 peripheral
      neuropathy. Bortezomib-associated peripheral neuropathy is manageable and
      reversible in most patients with relapsed myeloma. Dose modification using a
      specific guideline improves peripheral neuropathy management without adversely
      affecting outcome.

PMID- 19170678
TI  - The peptide-semicarbazone S-2209, a representative of a new class of proteasome
      inhibitors, induces apoptosis and cell growth arrest in multiple myeloma cells.
AB  - Bortezomib is the first approved member of a new class of anti-myeloma agents,
      the proteasome inhibitors. Further proteasome inhibitors are needed to optimise
      this promising treatment option. S-2209 [1-[1-{1-[(2,4-Dioxo-imidazolidin-1
      ylimino)-methyl]-2-phenyl-ethylcarbamoyl}-2-(1H-indol-3-yl)-ethylcarbamoyl]-2-(1H
      indol)] inhibits the chymotryptic activity of the human 20S proteasome (half
      maximal effective concentration, IC(50) approximately 220 nmol/l) which was
      determined by a proteasome inhibition assay. A nuclear factor kappaB inhibition
      assay revealed a half maximal effective concentration (EC(50)) of 0.9 micromol/l.
      The WST-1 growth assay showed inhibition of cell growth of all tested multiple
      myeloma (MM) cell lines with an IC(50) between 100 nmol/l and 600 nmol/l. Strong
      induction of apoptosis was seen in MM cells at nanomolar concentrations (IC(50)
      approximately 300 nm) as well as in primary myeloma cells. No induction of
      apoptosis was detected in peripheral blood mononuclear cells from healthy humans.
      Upregulation of p53, activation of JNK protein, and downregulation of Mcl-1 was
      revealed. Despite the administration of 15 mg S-2209/kg/d in wistar rats, no
      toxicity with respect to body weight, hepatic enzymes, creatinine or haemoglobin
      was seen. Proteasome inhibition in white blood cells isolated from the treated
      rats was higher in the S-2209 treated animals in comparison with the control
      animals treated with 0.1 mg/kg/d bortezomib. S-2209 is active in myeloma cells
      and shows a favourable toxicity profile in first in-vivo studies. S-2209 is a
      promising agent for further clinical development.

PMID- 19170679
TI  - Reduced plasma fibrinolytic capacity as a potential risk factor for a first
      myocardial infarction in young men.
AB  - Studies on the relationship between fibrinolysis and arterial thrombosis have
      been conflicting. Previously, we demonstrated that hypofibrinolysis, as measured
      by a plasma-based assay, increased the risk of venous thrombosis. The present
      study investigated increased clot lysis time (CLT) measured with the same assay
      as a risk factor for myocardial infarction in a case-control study including 421
      men with a first myocardial infarction and 642 controls below 70 years. CLT was
      strongly associated with body-mass index, lipid levels, blood pressure and C
      reactive protein. Overall, risk of myocardial infarction was 1.4-fold (95%
      confidence interval (CI) 1.0-1.9) increased for CLT in the fourth quartile
      (longest CLT) compared with the first quartile. After adjusting for
      cardiovascular risk factors this risk disappeared (OR 1.0, 95%CI 0.6-1.5). In men
      aged <50 years the association was pronounced (OR 3.2, 95%CI 1.5-6.7). After
      adjustment for cardiovascular risk factors the risk was nearly twofold increased
      (OR 1.8, 95%CI 0.7-4.8). In men aged > or = 50 years, no clear association
      between CLT and risk of myocardial infarction was found. Our study suggests that
      hypofibrinolysis increases the risk of a first myocardial infarction in young
      men, although the causality of this association remains to be determined.

PMID- 19170680
TI  - Clonal diversity in the myeloproliferative neoplasms: independent origins of
      genetically distinct clones.
AB  - This study looked for clonal diversity in patients with a myeloproliferative
      neoplasm associated with more than one acquired genetic lesion. A tyrosine kinase
      mutation and a cytogenetic lesion were present in the same clone in six of seven
      patients. By contrast, the genetic lesions were present in separate clones in all
      six patients with two tyrosine kinase pathway mutations. Moreover, in two
      patients the clones were genetically unrelated by X-chromosome inactivation
      studies. These data demonstrated clonal diversity in a subset of patients with
      early stage haematopoietic malignancy and showed, for the first time, that such
      clones may arise independently.

PMID- 19170681
TI  - Therapy of chemotherapy-induced peripheral neuropathy.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is still a common and disabling
      side effect of many chemotherapy agents in use today. Unfortunately, neither
      prophylactic strategies nor symptomatic treatments have proven useful yet. This
      review will discuss the diagnosis and evaluation of neuropathy in cancer
      patients, as well as reviewing the various prophylactic and symptomatic
      treatments that have been proposed or tried. However, sufficient evidence is
      lacking to recommend any of these treatments to patients suffering with CIPN.
      Therefore, the best approach is to treat symptomatically, and to start with broad
      spectrum analgesic medications such as non-steroidal anti-inflammatory drugs
      (NSAIDs). If NSAIDs fail, a reasonable second-line agent in properly selected
      patients may be an opioid. Unfortunately, even when effective in other types of
      neuropathic pain, anti-depressants and anticonvulsants have not yet proven
      effective for treating the symptoms of CIPN.

PMID- 19170682
TI  - Spinal cord neuronal pathology in multiple sclerosis.
AB  - The objective of this study was to assess neuronal pathology in the spinal cord
      in multiple sclerosis (MS), both within myelinated and demyelinated tissue.
      Autopsy material was obtained from 38 MS cases and 21 controls. Transverse
      sections were taken from three spinal cord levels and stained using Luxol Fast
      Blue/Cresyl Violet and myelin protein immunohistochemistry. Measurements of
      neuronal number and size were made for all neurons within the anterior horns of
      the gray matter. Neurons were classified as motoneurons or interneurons according
      to size criteria. In comparison with controls, both motoneuron and interneuron
      number were reduced in MS cases at the upper cervical (interneuron P = 0.0549;
      motoneuron P = 0.0073) and upper thoracic (interneuron P = 0.0507; motoneuron P =
      0.0144), but not the lumbar level. Interneuron cross-sectional area was reduced
      in MS cases at all levels (upper cervical, P = 0.0000; upper thoracic, P =
      0.0002; lumbar, P = 0.0337). Neuronal loss appears to be predominantly related to
      local gray matter plaques, whereas interneuron atrophy occurs in both myelinated
      and demyelinated areas.

PMID- 19170683
TI  - Immunolocalization of fascin, an actin-bundling protein and glial fibrillary
      acidic protein in human astrocytoma cells.
AB  - Fascin is a 55-kDa globular protein that functions to organize filamentous-actin
      into parallel bundles. A role for fascin in cell migration has led to its study
      in many tumor types. In this report, we investigate fascin in astrocytomas. We
      show that fascin is expressed in astrocytes and in a panel of human astrocytoma
      cell lines. Immunofluorescence analysis demonstrates that fascin and the
      intermediate filament protein, glial fibrillary acidic protein (GFAP), are both
      expressed in the perinuclear region and within cytoplasmic processes of
      astrocytes and astrocytoma cells. Amino acid residues within the NH2 terminus of
      GFAP can undergo phosphorylation; these modifications regulate intermediate
      filament disassembly and occur during cytokinesis. We show that fascin and
      specific phosphorylated species of GFAP colocalize within dividing cells.
      Finally, we demonstrate that fascin co-immunoprecipitates with GFAP and that
      immunocomplex formation is preferential for GFAP phosphorylated at serine
      residues 8 and 13. These data show that fascin and GFAP are immunolocalized
      regionally within cells and tumors of astrocytic origin and suggest that their
      binding may occur during dynamic reorganization of intermediate filaments.

PMID- 19170684
TI  - Modified C-reactive protein is expressed by stroke neovessels and is a potent
      activator of angiogenesis in vitro.
AB  - Native C-reactive protein (nCRP) is a pentameric oligo-protein and an acute phase
      reactant whose serum expression is increased in patients with inflammatory
      disease. We have identified by immunohistochemistry, significant expression of a
      tissue-binding insoluble modified version or monomeric form of CRP (mCRP)
      associated with angiogenic microvessels in peri-infarcted regions of patients
      studied with acute ischaemic stroke. mCRP, but not nCRP was expressed in the
      cytoplasm and nucleus of damaged neurons. mCRP co-localized with CD105, a marker
      of angiogenesis in regions of revascularisation. In vitro investigations
      demonstrated that mCRP was preferentially expressed in human brain microvessel
      endothelial cells following oxygen-glucose deprivation and mCRP (but not column
      purified nCRP) associated with the endothelial cell surface, and was angiogenic
      to vascular endothelial cells, stimulating migration and tube formation in
      matrigel more strongly than fibroblast growth factor-2. The mechanism of signal
      transduction was not through the CD16 receptor. Western blotting showed that mCRP
      stimulated phosphorylation of the key down-stream mitogenic signalling protein
      ERK1/2. Pharmacological inhibition of ERK1/2 phosphorylation blocked the
      angiogenic effects of mCRP. We propose that mCRP may contribute to the
      neovascularization process and because of its abundant presence, be important in
      modulating angiogenesis in both acute stroke and later during neuro-recovery.

PMID- 19170685
TI  - Signalling pathways in the pathogenesis of Cryptococcus.
AB  - Efficient communication with the environment is critical for all living
      organisms. Fungi utilize complex signalling systems to sense their environments
      and control proliferation, development and in some cases virulence. Well-studied
      signalling pathways include the protein kinase A/cyclic AMP (cAMP), protein
      kinase C (PKC)/mitogen-activated protein kinase (MAPK), lipid signalling
      cascades, and the calcium-calcineurin signalling pathway. The human pathogenic
      basidiomycetous fungus Cryptococcus neoformans deploys sensitive signalling
      systems to survive in the human host, leading to life-threatening
      meningoencephalitis. Known virulence traits of this fungus, including the
      antioxidant melanin production, the antiphagocytic polysaccharide capsule and the
      ability to grow at 37 degrees C, are orchestrated by complex signalling networks,
      whose understanding is crucial to better treat, diagnose and prevent
      cryptococcosis.

PMID- 19170686
TI  - Two-photon microscopy of host-pathogen interactions: acquiring a dynamic picture
      of infection in vivo.
AB  - Two-photon (2P) microscopy has become increasingly popular among immunologists
      for analysing single-cell dynamics in tissues. Researchers are now taking 2P
      microscopy beyond the study of model antigen systems (e.g. ovalbumin
      immunization) and are applying the technique to examine infection in vivo. With
      the appropriate fluorescent probes, 2P imaging can provide high-resolution spatio
      temporal information regarding cell behaviour, monitor cell functions and assess
      various outcomes of infection, such as host cell apoptosis or pathogen
      proliferation. Imaging of transgenic and knockout mice can be used to probe
      molecular mechanisms governing the host response to infection. From the microbe
      side, imaging genetically engineered mutant strains of a pathogen can test the
      roles of specific virulence factors in pathogenesis. Here, we discuss recent work
      that has applied 2P microscopy to study models of infection and highlight the
      tremendous potential that this approach has for investigating host-pathogen
      interactions.

PMID- 19170687
TI  - Placebo efficacy in childhood and adolescence migraine: an analysis of double
      blind and placebo-controlled studies.
AB  - Studies on the treatment of migraine in children and adolescents are rare and
      difficult to design. In particular, the high placebo response in some trials
      makes it difficult to prove efficacy of a verum drug. We analysed all available
      placebo-controlled trials on acute and on prophylactic migraine treatment in
      children and adolescents with respect to different placebo rates (pain free and
      pain relief at 2 h; rate of responders with >or= 50% attack frequency decrease).
      We identified eight crossover and 11 parallel group trials on acute treatment.
      The placebo response rates were considerably lower in crossover trials than in
      parallel group trials (19.2% vs. 27.1% for pain free after 2 h and 39.4% vs.
      56.9% for pain relief after 2 h). In the 10 prophylactic trials included in this
      analysis, only a small trend towards a lower placebo rate in crossover trials
      could be observed. Further significant factors associated with a lower placebo
      rate in childhood and adolescence trials on the acute treatment of migraine were
      single-centre (vs. multicentre) trials and small sample size. Age and sex were
      not associated with the placebo response. Our study suggests that parallel group
      trials on the acute treatment of migraine in children and adolescents show a very
      low therapeutic gain due to a high placebo rate. The verum response rates,
      however, are very similar to those seen in adulthood trials. In conclusion, trial
      designs on the acute and prophylactic treatment of migraine in children and
      adolescents should consider the specific findings of this analysis in order to
      exhibit a higher probability of showing significant differences between placebo
      and verum drug.

PMID- 19170688
TI  - Effects of visual pathway lesions on the visual aura of migraine.
AB  - The aim was to to determine if the visual aura of migraine is altered by disease
      of the afferent visual pathways and if visual aura changes are associated with
      pre- or postgeniculate lesions. Functional neuroimaging during migraine
      demonstrates primary visual/extrastriate cortex as an anatomical substrate of
      visual aura. Neuro-ophthalmological records (including kinetic and static
      perimetry) of 25 patients with visual loss and typical aura with or without
      migraine headache were reviewed. Twenty-five patients (16 women, nine men) (mean
      age 59.8 years) with typical aura had visual loss from pregeniculate (72%) or
      postgeniculate lesions (28%). Eight patients (four postgeniculate cerebrovascular
      accidents or arteriovenous malformations, two lifelong optic
      neuropathy/retinopathy, one childhood ocular trauma, one anisometropic amblyopia)
      reported absence or alteration of visual aura. Postgeniculate lesions were
      significantly associated (P = 0.017) with visual aura changes. The association of
      postgeniculate lesions with altered auras points to a postgeniculate effect on
      aura appearance (consistent with functional neuroimaging findings). Although
      statistically significant, this series' association of postgeniculate disease and
      aura changes is even more robust (P = 0.0002) when structural changes of ocular
      dominance columns are posited in three patients with optic neuropathy,
      retinopathy and keratopathy of congenital or childhood origin.

PMID- 19170689
TI  - Effective prophylactic treatments of migraine lower plasma glutamate levels.
AB  - The role of glutamate in migraine treatment has not been much studied, even if
      this amino acid seems to be crucial in the pathogenesis of migraine. Our aim was
      to determine if there were differences in the plasma levels of glutamate between
      migraine patients and control subjects and if plasma levels of glutamate in
      migraine patients modified after 8 weeks of prophylactic treatment. We studied 24
      patients with diagnosis of migraine without aura according to International
      Classification of Headache Disorders, 2nd edn criteria, and 24 age- and sex
      matched healthy subjects, as controls. In migraineurs the level of glutamate was
      measured before and after 8 weeks of prophylactic treatment (topiramate 50
      mg/day, five patients; amitriptyline 20 mg/day, seven patients; flunarizine 5
      mg/day, seven patients; propranolol 80 mg/day, five patients). Venous blood
      samples were taken in the morning, after overnight fasting, and at least 3 days
      after the last migraine day. Glutamate levels were measured by means of a
      fluorimetric detector high-pressure liquid chromatographic method. Plasma levels
      of glutamate were significantly higher in migraine patients-either before (61.79
      +/- 18.75 micromol/l) or after prophylactic treatment (17.64 +/- 5.08 micromol/l)
      than in controls (9.36 +/- 2.1 micromol/l) (P < 0.05, anova followed by Newman
      Keuls' test). After prophylactic treatment, with headache frequency reduced,
      plasma glutamate levels were significantly lower in the same patient with respect
      to the prior baseline level (P < 0.0001, Student's t-test for paired data),
      without any differences depending on the kind of prophylactic drug. Effective
      prophylactic treatments reducing high glutamate plasma levels found in migraine
      patients could act on the underlying mechanism that contributes to cause
      migraine. Plasma glutamate level monitoring in migraine patients might serve as a
      biomarker of response to treatments and as an objective measure of disease
      status.

PMID- 19170690
TI  - Transient hypnic headache syndrome in a patient with bipolar disorder after the
      withdrawal of long-term lithium treatment: a case report.

PMID- 19170691
TI  - Migraine with aura induced by artificial microbubbles.

PMID- 19170692
TI  - Fibromyalgia comorbidity in primary headaches.
AB  - Fibromyalgia syndrome (FMS) is a chronic pain condition of unknown aetiology
      characterized by diffuse pain and tenderness at tender points. The aim of the
      study was to assess the prevalence and clinical features of FMS in the different
      forms of primary headaches, in a tertiary headache centre. Primary headache
      patients (n = 217) were selected and submitted to the Total Tenderness Score,
      anxiety and depression scales, Migraine Disability Assessment, allodynia
      questionnaire, Short Form 36 Health Survey and the Medical Outcomes Study-Sleep
      Scale. In patients with FMS, the Multidimensional Assessment of Fatigue, the Pain
      Visual Analog Scale, the Manual Tender Point Survey and the Fibromyalgia Impact
      Questionnaire were employed. FMS was present in 36.4% of patients and prevailed
      significantly in tension-type headache and in patients with higher headache
      frequency. Headache frequency, pericranial muscle tenderness, anxiety and sleep
      inadequacy were especially associated with FMS comorbidity. In the FMS patients,
      fatigue and pain at tender points were significantly correlated with headache
      frequency. FMS seems increasingly prevalent with increased headache frequency,
      for the facilitation of central sensitization phenomena favoured by anxiety and
      sleep disturbances.

PMID- 19170693
TI  - Treatment of cluster headache in pregnancy and lactation.
AB  - Cluster headache is a rare disorder in women, but has a serious impact on the
      affected woman's life, especially on family planning. Women with cluster headache
      who are pregnant need special support, including the expertise of an experienced
      headache centre, an experienced gynaecologist and possibly a teratology
      information centre. The patient should be seen through all stages of the
      pregnancy. A detailed briefing about the risks and safety of various treatment
      options is mandatory. In general, both the number of medications and the dosage
      should be kept as low as possible. Preferred treatments include oxygen,
      subcutaneous or intranasal sumatriptan for acute pain and verapamil and
      prednisone/prednisolone as preventatives. If there is a compelling reason to
      treat the patient with another preventative, gabapentin is the drug of choice.
      While breastfeeding, oxygen, sumatriptan and lidocaine for acute pain and
      prednisone/prednisolone, verapamil, and lithium as preventatives are the drugs of
      choice. As the individual pharmacokinetics differ substantially, adverse drug
      effects should be considered if unexplained symptoms occur in the newborn.

PMID- 19170694
TI  - Comorbidity of headache, other pain and RLS: do analgesics play a part?

PMID- 19170695
TI  - Platelet dopamine: D2 receptor binding in patients with migraine.
AB  - Clinical, genetic and pharmacological evidences suggest an abnormality of the
      dopaminergic system in the pathogenesis of migraine. Direct evidence of an
      abnormal metabolism of dopamine in migraine, however, is lacking. Platelets are a
      useful model to understand brain dopaminergic mechanisms. The present study has
      been undertaken to study the status of platelet dopamine receptor binding by
      carrying out radioligand receptor binding assay. Binding of (3)H-spiperone to
      platelet membranes, known to label dopamine (DA)-D2 receptors, was conducted in
      20 patients with migraine and an equal number of healthy controls. The
      equilibrium dissociation constant (Kd) in patients with migraine (1.71 +/- 0.19
      nM) was found to be significantly lower (P < 0.001) as compared with controls
      (3.14 +/- 0.33 nM). However, no significant change was observed in the maximal
      number of binding sites (Bmax) in patients with migraine. No relationship of Kd
      with type of migraine, presence of vomiting, family history, frequency of attack,
      duration of illness and menstrual migraine was observed. The findings of the
      present study provide support for the involvement of the dopaminergic system in
      migraine.

PMID- 19170696
TI  - Stretch reflex and pressure pain thresholds in chronic tension-type headache
      patients and healthy controls.
AB  - To compare the jaw-stretch reflex and pressure pain thresholds (PPT) in chronic
      tension-type headache (CTTH) patients and healthy controls, 30 patients (15 male
      and 15 female) and 30 age- and sex-matched healthy subjects were investigated.
      Stretch reflexes were recorded in the temporalis and masseter muscles and PPT was
      determined in the anterior temporalis, splenius capitis and masseter muscles. The
      results showed that the amplitude of the stretch reflex in CTTH patients was
      higher compared with control subjects (P < 0.045), and higher in women compared
      with men in the right and left anterior temporalis muscles (P < 0.009). There
      were no differences in the PPT value between CTTH and control subjects (P >
      0.509), whereas women showed significantly lower PPT measurements (P < 0.046).
      The results demonstrated a facilitation of the stretch reflex pathways in CTTH
      patients that is unrelated to measures of pericranial sensitivity.

PMID- 19170697
TI  - Association of benign recurrent vertigo and migraine in 208 patients.
AB  - The aim of this study was to determine the association of benign recurrent
      vertigo (BRV) and migraine, using standardized questionnaire-based interview of
      208 patients with BRV recruited through a University Neurotology clinic. Of 208
      patients with BRV, 180 (87%) met the International Classification of Headache
      Disorders 2004 criteria for migraine: 112 migraine with aura (62%) and 68 without
      aura (38%). Twenty-eight (13%) did not meet criteria for migraine. Among patients
      with migraine, 70% experienced headache, one or more auras, photophobia, or
      auditory symptoms with some or all of their vertigo attacks, meeting the criteria
      for definite migrainous vertigo. Thirty per cent never experienced migraine
      symptoms concurrent with vertigo attacks. These met criteria for probable
      migrainous vertigo. Among patients without migraine, 21% experienced either
      photophobia or auditory symptoms with some or all of their vertigo attacks; 79%
      experienced only isolated vertigo. The age of onset and duration of vertigo
      attacks did not differ significantly between patients with (34 +/- 1.2 years) and
      patients without migraine (31 +/- 3.0 years). In patients with migraine, the age
      of onset of migraine headache preceded the onset of vertigo attacks by an average
      of 14 years and aura preceded vertigo by 8 years. The most frequent duration of
      vertigo attacks was between 1 h and 1 day. Benign recurrent vertigo is highly
      associated with migraine, but a high proportion of patients with BRV and migraine
      never have migraine symptoms during their vertigo attacks. Other features such as
      age of onset and duration of vertigo are similar between patients with or without
      migraine.

PMID- 19170698
TI  - Prevalence and clinical characteristics of headache in medical students of the
      University of Lagos, Nigeria.
AB  - We investigated the 1-year prevalence, clinical features and mode of treatment of
      headache in medical students of the University of Lagos, Nigeria, using a self
      administered headache questionnaire. Headache prevalence was 46.0% and was
      significantly higher in women than in men (62.8% vs. 34.1%). Prevalence of
      tension-type headache was higher than that of migraine (18.1% vs. 6.4%). Although
      tension-type headache had a similar prevalence in both sexes (male 17.3%, female
      19.2%), migraine was three times more common in women (10.9% vs. 3.2%). A family
      history of headache was present in 22.0%. Only 4.6% sought medical assistance,
      whereas 68.2% took non-prescription drugs, mainly simple analgesics. Specific
      drugs for migraine and tension-type headache were rarely used. In conclusion, 1
      year headache prevalence is high among medical students at this university. The
      low consultation rate and the rarity of usage of specific anti-headache drugs
      probably reflect inadequacies in the management of primary headaches in this
      population.

PMID- 19170700
TI  - Re. Prevalence and associated factors for episodic and chronic daily headache in
      the Colombian population.

PMID- 19170702
TI  - Idiopathic intracranial hypertension without papilloedema in headache sufferers.

PMID- 19170703
TI  - Syndrome of transient headache and neurological deficits with CSF lymphocytosis
      (HaNDL) associated with recent human herpesvirus-6 infection.

PMID- 19170704
TI  - Clinical value of the first automated TSH receptor autoantibody assay for the
      diagnosis of Graves' disease (GD): an international multicentre trial.
AB  - BACKGROUND: Most recently, a new rapid and fully automated
      electrochemiluminescence immunoassay for the determination of TSH receptor
      autoantibodies (TRAb) based on the ability of TRAb to inhibit the binding of a
      human thyroid-stimulating monoclonal antibody (M22) has been established.
      OBJECTIVE: To evaluate this assay system in clinical routine based on an
      international multicentre trial and to compare the results with other established
      TRAb assays. PATIENTS AND MEASUREMENTS: Totally 508 Graves' disease (GD), 142
      autoimmune thyroiditis, 107 subacute thyroiditis, 109 nonautoimmune nodular
      goitre, 23 thyroid cancer patients and 446 normal controls were retrospectively
      evaluated. RESULTS: ROC plot analysis revealed an area under curve of 0.99 (95%
      CI: 0.99-1.0) indicating a high assay sensitivity and specificity. The highest
      sensitivity (99%) and specificity (99%) was seen at a cut-off level of 1.75 IU/l.
      Here, the calculated positive predictive value was 95%, whereas the negative
      predictive value was 100%. Applying the ROC plot-derived cut-off of 1.75 IU/l we
      found a sensitivity for TRAb positivity within the group of newly diagnosed GD
      patients of 97% which is in accordance to the sum of different nonautomated
      porcine TSH receptor-based assays with a sensitivity of 94% indicating an
      excellent analytical performance of the new assay format. Detailed comparison of
      the automated and the sum of manual assays revealed a near identical specificity.
      CONCLUSION: Our results demonstrate that this new assay system has a high
      sensitivity for detecting GD and specificity for discriminating from other
      thyroid diseases. This assay may represent the future technology for rapid fully
      automated TRAb detection.

PMID- 19170705
TI  - Homozygous nonsense and frameshift mutations of the ACTH  receptor in children
      with familial glucocorticoid deficiency  (FGD) are not associated with long-term
      mineralocorticoid  deficiency.
AB  - OBJECTIVE: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive
      disease characterized by isolated glucocorticoid deficiency with preserved
      mineralocorticoid secretion. Mutations in the ACTH receptor (MC2R) account for
      approximately 25% of all FGD cases, but since these are usually missense
      mutations, a degree of receptor function is frequently retained. A recent report,
      however, suggested that disturbances in the renin-aldosterone axis were seen in
      some patients with potentially more severe MC2R mutations. Furthermore, MC2R
      knock out mice have overt aldosterone deficiency and hyperkalaemia despite
      preservation of a normal zona glomerulosa. We wished to determine whether a group
      of patients with severe nonsense mutations of the MC2R exhibited evidence of
      mineralocorticoid deficiency, thereby challenging the conventional diagnostic
      feature of FGD which might result in diagnostic misclassification. DESIGN:
      Clinical review of patients with nonsense MC2R mutations. PATIENTS: Between 1993
      and 2008, 164 patients with FGD were screened for mutations in the MC2R. Totally
      42 patients (34 families) were found to have mutations in the MC2R. Of these, 6
      patients (4 families) were found to have homozygous nonsense or frameshift
      mutations. RESULTS: Mild disturbances in the renin-angiotensin-aldosterone axis
      were noted in four out of six patients, ranging from slightly elevated plasma
      renin levels to low aldosterone levels, although frank mineralocorticoid
      deficiency or electrolyte disturbance were not found. No patient required
      fludrocortisone replacement. CONCLUSION: Severe nonsense and frameshift MC2R
      mutations are not associated with clinically significant mineralocorticoid
      deficiency and are thus unlikely to require long-term mineralocorticoid
      replacement.

PMID- 19170706
TI  - Bone mineral density and bone turnover in Romanian children and young adults with
      classical 21-hydroxylase deficiency are influenced by glucocorticoid replacement
      therapy.
AB  - OBJECTIVE: It remains controversial if glucocorticoid replacement therapy impairs
      bone mineral density (BMD) in young patients with 21-hydroxylase deficiency. We
      aimed to analyze the impact of treatment variables, phenotype and genotype on BMD
      and bone metabolism in these patients. DESIGN: Cross-sectional study.
      MEASUREMENTS: Twenty-eight Caucasian patients with classical 21-hydroxylase
      deficiency (5-39 years). Clinical parameters, hormonal status, osteocalcin (OC),
      C-terminal telopeptide of type I collagen (CTX), genotype and lumbar BMD (Z
      scores) were assessed. Cumulative and mean hydrocortisone equivalent doses were
      calculated for the entire treatment period. RESULTS: Patients with severely
      reduced BMD Z-scores (< or = -2.5 SD) had significantly higher mean/cumulative
      glucocorticoid doses compared to patients with moderately reduced (P = 0.003/P =
      0.026) and normal Z-scores (> -1 SD) (P = 0.005/P = 0.011). Mean hydrocortisone
      equivalent doses > 20 mg/m(2)/day led to significantly lower lumbar BMD Z-scores
      (-2.16 +/- 1.4 SD) vs. doses </= 20 mg/m(2)/day (-0.59 +/- 1.25 SD) (P = 0.008).
      BMD correlated negatively with mean/cumulative glucocorticoid doses and treatment
      duration. OC (86.45 +/- 37.45 ng/ml) and CTX (1.45 +/- 0.43 ng/ml) were
      significantly increased compared to an age- and sex-matched control group in
      patients with active growth; only CTX was slightly increased in patients who
      completed growth. CONCLUSIONS: High cumulative and mean glucocorticoid doses
      negatively impact on BMD in children and young adults with classical 21
      hydroxylase deficiency. Substitution therapy should be adapted particularly at
      this life period to prevent bone loss.

PMID- 19170707
TI  - Functional analysis of two rare CYP21A2 mutations detected in Italian patients
      with a mildest form of congenital adrenal hyperplasia.
AB  - BACKGROUND: More than 90% of all cases of congenital adrenal hyperplasia (CAH)
      result from steroid 21-hydroxylase gene (CYP21A2) mutations. Most of these
      mutations result from intergenic recombinations between CYP21A2 and closely
      linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion
      account for 5-10% of 21-hydroxylase deficiency alleles. OBJECTIVE: Functional
      analysis of two novel CYP21A2 missense mutations (p.R224W and p.D407N) was
      performed. DESIGN: Our study was composed of two Italian patients suffering from
      a very mild form of nonclassic CAH (NC-CAH). To assay the enzymatic activity of
      mutants, the in vitro analysis was performed in transiently transfected COS-1
      cells. RESULTS: The residual activities obtained for p.R224W and p.D407N mutants
      allow their classification as NC-CAH mutations. These results correlate with the
      rate of severity of the patients' disease. CONCLUSIONS: In this paper, we report
      two novel CYP21A2 mutations in two Italian individuals affected by 21-hydroxylase
      deficiency. Based on the functional in vitro analysis we can classify these
      mutations as NC-CAH variants.

PMID- 19170708
TI  - Effects of recombinant human LH and hCG on serum and urine LH and androgens in
      men.
AB  - CONTEXT: The administration of gonadotrophins is prohibited in sport but the
      effect in men of recently available recombinant hCG and LH on serum and urine
      concentrations of gonadotrophins and androgens has not been systematically
      evaluated in the antidoping context. OBJECTIVE: To determine the time-course of
      recombinant LH (rhLH) and hCG (rhCG) on blood and urine hormone profiles in men
      to develop effective tests to detect rhLH and rhCG doping. DESIGN: Two randomized
      controlled studies with a 2 x 2 factorial design. SETTING: Academic research
      centre. PARTICIPANTS: Healthy male volunteers aged 18-45 years. INTERVENTIONS: In
      the rhLH study, men were randomized into (i) either of two single doses of rhLH
      (75 IU or 225 IU), and (ii) suppression of endogenous LH and testosterone by
      nandrolone or no suppression. In the rhCG study, men were randomized into (i)
      either of two single doses of rhCG (250 or 750 microg), and (ii) suppression of
      endogenous LH and testosterone by nandrolone decanoate (ND) or no suppression. ND
      suppression comprised a single dose of 200 mg ND 3 days prior to, and in the rhCG
      study an additional dose 1 day after gonadotrophin injection. MAIN OUTCOME
      MEASURES: Serum and urine hCG, LH, T, T : LH ratio, urine epitestosterone (E) and
      urine T : E ratio. RESULTS: Neither rhLH dose produced a significant increase in
      serum or urine LH or T or in the T : E or T : LH ratios regardless of ND-induced
      suppression of endogenous LH and T. Nor did an even higher dose (750 IU) in three
      healthy men with unsuppressed gonadal axis. These findings were confirmed with
      two different commercial LH immunoassays together with adjustment for any
      influence of urine sediment and dilution. Both rhCG doses produced a steep, dose
      proportional increase in serum and urine hCG with increases in serum and urine T
      and suppression of serum and urine LH, regardless of hCG dose. Serum but not
      urine T was lowered by ND suppression. The T : LH ratio showed a progressive
      increase unrelated to rhCG dose or ND suppression, whereas both rhCG and ND
      suppression minimally increased T : E ratio. CONCLUSIONS: Both rhCG doses produce
      a striking increase in serum hCG and T with suppression of serum LH but, at
      single doses up to 750 IU, rhLH has no influence on serum or urine LH or T.
      Effective rhLH doping, which relies on a sustained increases in endogenous T,
      would require much higher and more frequent daily rhLH doses. Use of LH
      immunoassays optimized for serum to detect rhLH doping by urine LH measurement
      requires more standardization and validation and, at present, is unreliable. The
      T : LH ratio is, however, a useful screening test for hCG doping although its
      utility requires further evaluation.

PMID- 19170709
TI  - Quality of life in children and adolescents 1-year after cure of Cushing
      syndrome: a prospective study.
AB  - OBJECTIVE: Cushing syndrome (CS) in children is associated with symptoms that may
      impair health related quality of life (HRQL). There are no prospective reports of
      HRQL in children with CS. METHODS: Prospective study of 40 children (mean age 13
      +/- 3.2 years) with CS evaluated prior to and 1-year post-treatment. The Child
      Health Questionnaire (CHQ) was used to assess HRQL; Wechsler Intelligence Scale
      for Children (WASI) was used to assess cognitive function, and patient-reported
      symptoms were assessed with a CS symptom checklist. RESULTS: Active CS was
      associated with low physical and psychosocial summary scores compared to US
      population data (P < 0.001). Despite improvement from pre- to 1-year postcure,
      residual impairment remained in physical summary and function, and role-physical,
      global health and emotional impact (parent) scores. Incomplete recovery of
      adrenal function at 1-year post-treatment was associated with impaired scores.
      WASI IQ scores declined and a correlation was noted between age at first
      evaluation and IQ score changes. Most self-reported CS symptoms showed
      improvement, but forgetfulness, unclear thinking and decreased attention span did
      not improve after cure of CS. CONCLUSION: CS in children and adolescents is
      associated with impaired HRQL, with residual impairment 1 year after cure. Our
      results also suggest that younger children are more likely to experience negative
      changes in cognitive function. HRQL is an important outcome measure in children
      and adolescents with CS and identification of factors that contribute to HRQL may
      help to diminish the physical and psychological burden of disease in this
      population of patients.

PMID- 19170710
TI  - Silent subtype 3 pituitary adenoma: a clinicopathologic analysis of the Mayo
      Clinic experience.
AB  - BACKGROUND: Macroadenomas represent 50% of pituitary tumours and are often (30%)
      nonfunctioning. Their immunophenotype suggests differentiation toward a specific
      pituitary cell line. A substantial proportion of tumours with particularly
      aggressive behaviour are so called 'silent subtype 3 adenoma'. Its diagnosis
      requires ultrastructural confirmation. Although once included among silent
      corticotroph adenomas, this aggressive, morphologically distinctive tumour is now
      recognized as a major form of plurihormonal adenoma and, in fact, some patients
      might present with clinical hormonal excess. The cytogenesis and pathobiology of
      silent subtype 3 adenomas is unsettled. OBJECTIVE: We undertook a systematic
      clinicopathologic examination of the Mayo Clinic experience with this poorly
      understood tumour. DESIGN: This retrospective, single institution study found 27
      confirmed examples of silent subtype 3 adenoma, a frequency of 0.9% of adenomas.
      Despite histologic and immunophenotypic variation, their ultrastructural features
      were diagnostic and the sole basis for case inclusion. RESULTS: The study group
      was comprised of 16 men (59%) and 11 women (41%); two patients (7%) had
      definitive diagnosis of multiple endocrine neoplasia type 1 (MEN1). Three tumours
      (11%) were discovered incidentally. Nine patients each (38%) presented with
      headaches or visual field loss. Endocrine hyperfunction was noted in eight cases
      (30%), including GH excess in five (19%) and clinically significant PRL elevation
      in three (11%). Hypogonadism was noted in 17 cases (63%) and growth arrest in one
      (4%). All tumours were macroadenomas; 16 (60%) showed radiographic evidence of
      invasion. Most tumours were plurihormonal, featuring immunoreactivity for PRL
      (17), GH (15), TSH (16) or ACTH (3); only one lesion was immunonegative. Although
      a gross total resection was achieved in 19 cases (70%), re-operation for
      recurrence(s) was required in seven of these (37%). Follow-up (mean, 69 months)
      showed a high (59%) rate of persistent or recurrent of tumour. Overall, 14
      patients (54%) underwent radiotherapy after surgical treatment: three patients
      (12%) for substantial residual tumour, eight (31%) as adjuvant therapy and three
      (12%) for tumour regrowth. CONCLUSION: Silent subtype 3 adenoma, a plurihormonal
      tumour, is rare and aggressive in nature. This adenoma must be considered in the
      differential of often clinically nonfunctioning but plurihormonal adenomas
      featuring variable cytologic atypia. Electron microscopy is required for
      confirmation of the diagnosis. The cytogenesis of silent subtype 3 adenoma
      remains unsettled.

PMID- 19170711
TI  - Identification, characterization and rescue of a novel vasopressin-2 receptor
      mutation causing nephrogenic diabetes insipidus.
AB  - OBJECTIVE: X-linked nephrogenic diabetes insipidus (XNDI), caused by mutations in
      the V2 vasopressin receptor (V2R), is clinically distinguished from central
      diabetes insipidus (CDI) by elevated serum vasopressin (AVP) levels and
      unresponsiveness to 1-desamino-8-d-arginine vasopressin (DDAVP). We report two
      infants with XNDI, and present the characterization and functional rescue of a
      novel V2R mutation. PATIENTS: Two male infants presented with poor growth and
      hypernatraemia. Both patients had measurable pretreatment serum AVP and polyuria
      that did not respond to DDAVP, suggesting NDI. However, both also had absent
      posterior pituitary bright spot on MRI, which is a finding more typical of CDI.
      METHODS: The AVPR2 gene encoding V2R was sequenced. The identified novel missense
      mutation was re-created by site-directed mutagenesis and expressed in HEK293
      cells. V2R activity was assessed by the ability of transfected cells to produce
      cAMP in response to stimulation with DDAVP. Membrane localization of V2R was
      assessed by fluorescence microscopy. RESULTS: Patient 1 had a deletion of AVPR2;
      patient 2 had the novel mutation L57R. In transiently transfected HEK293 cells,
      DDAVP induced detectable but severely impaired L57R V2R activity compared to
      cells expressing wild-type V2R. Fluorescence microscopy showed that myc-tagged
      wild-type V2R localized to the cell membrane while L57R V2R remained
      intracellular. A nonpeptide V2R chaperone, SR121463, partially rescued L57R V2R
      function by allowing it to reach the cell membrane. CONCLUSIONS: L57R V2R has
      impaired in vitro activity that can be partially improved by treatment with a V2R
      chaperone. The posterior pituitary hyperintensity may be absent in infants with
      XNDI.

PMID- 19170712
TI  - What should be done in an operating room when an insulinoma cannot be found?
AB  - Insulinoma is the most common (functioning) islet cell tumour of the pancreas and
      is highly curable with accurate localization and precise extirpation of the often
      benign, solitary lesion. Although previous reports describe high success rates
      without pre-operative localization, more recent recognition of the overlap among
      causes of endogenous hyperinsulinism, coupled with the deleterious long-term
      effects of blind distal pancreatectomy and re-operation, mandate the need for
      precise pre-operative localization or regionalization of the tumour(s). If these
      criteria have not been met and the surgeon finds him/herself in the operating
      room without a localized or regionalized tumour, the operation should be
      concluded without resection, the diagnosis reconfirmed, and a calcium stimulation
      test performed. At experienced centres, this can be often carried out within 24
      48 h and the patient returned to the operating room for a gradient-guided
      resection. Intraoperative venous sampling for insulin might be an option in the
      future but its accuracy has not been validated in sufficient numbers of patients
      to date.

PMID- 19170713
TI  - Statin therapy as the fundamental therapy for cardiovascular prevention: be
      careful.

PMID- 19170714
TI  - Hyperinsulinaemic hypoglycaemia associated with a heterozygous missense mutation
      of R1174W in the insulin receptor (IR) gene.
AB  - BACKGROUND: Mutations in the insulin receptor (IR) gene are known to cause severe
      insulin resistance. Although clinical features due to a mutation can be diverse,
      hypoglycaemia is found in some cases. A family with a female proband diagnosed
      with type A insulin resistance syndrome was studied. Clinical characteristics
      were compared with the Arginine1174Glutamine (R1174N) mutation reported in the
      literature. METHODS: The proband was a 16-year-old girl who was presented with
      intermittent hypoglycaemia, hirsutism, darkened skin, acne and oligomenorrhoea. A
      5-h oral glucose tolerance test (OGTT), intravenous glucose tolerance test and
      continuous glucose monitoring system were performed for evaluation of glucose
      metabolism and insulin secretion. Results from a hyperinsulinaemic euglycaemic
      clamp on the proband were compared to nine normal glucose tolerance (NGT)
      controls. The IR gene of the proband, along with her parents and two dizygotic
      twin brothers were scanned for mutations by direct sequencing. RESULTS: Elevated
      serum insulin and insulin : C-peptide ratios were found in the proband, the
      father and one of the twin brothers, carried a heterozygous missense mutation of
      Arginine1174Tryptophan (R1174W) in exon20 of the IR gene. The clamp study showed
      that the nonoxidative glucose disposal rates of the proband were near zero, and
      that the metabolic clearance rate for insulin was markedly reduced. CONCLUSIONS:
      R1174 of the IR gene may be a candidate locus for hyperinsulinaemic
      hypoglycaemia. Clinical heterogeneity is not uncommon within families as well as
      among mutation carriers with different amino acid replacements. More pedigrees
      and long-term follow-up data are needed to document the evolution of beta-cell
      function and clarify the role of R1174 on insulin resistance and
      hyperinsulinaemic hypoglycaemia.

PMID- 19170715
TI  - Testosterone stimulates extra-hepatic but not hepatic fat oxidation (Fox):
      comparison of oral and transdermal testosterone administration in hypopituitary
      men.
AB  - BACKGROUND: Fat mass is increased in hypogonadal men and the changes are reversed
      by testosterone replacement. Testosterone administration enhances whole body fat
      oxidation (Fox). Fat is oxidized in the liver and in extra-hepatic tissues.
      OBJECTIVE: To determine whether the stimulation of Fox by testosterone arises
      primarily from the liver or from extra-hepatic tissues. DESIGN/PATIENTS: This was
      an open-label cross-over study. Thirteen men with hypopituitarism (age 53.1 +/-
      4.1 years) with both growth hormone (GH) and testosterone deficiency were studied
      sequentially after 2 weeks of treatment with transdermal testosterone (5 mg), no
      treatment, and stepwise incremental doses of oral crystalline testosterone (10,
      20, 40 and 80 mg) in the absence of GH replacement. MEASUREMENTS: Serum
      testosterone, IGF-I, metabolic effects [resting energy expenditure (REE) and
      Fox], SHBG, and thyroid binding globulin (TBG) as markers of excessive hepatic
      androgen exposure, were measured at the end of each treatment period. RESULTS:
      When compared to the no-treatment phase, mean blood testosterone levels rose into
      the physiological range after transdermal testosterone delivery but did not
      significantly change after 10, 20, 40 or 80 mg oral testosterone treatment. Blood
      SHBG and TBG fell significantly with 80 mg oral testosterone dose but were
      unaffected by any other testosterone treatment. Fox increased significantly with
      transdermal but not with any dose of oral testosterone. Mean plasma IGF-I and REE
      were unaffected by testosterone, regardless of the route or dose. CONCLUSIONS:
      Short-term testosterone administration does not stimulate hepatic fat oxidation
      but enhances whole body fat oxidation by acting on extra-hepatic tissues.

PMID- 19170717
TI  - Clinical complications following thyroid fine-needle biopsy: a systematic review.
AB  - Thyroid fine-needle biopsy (FNB) is a simple, reliable, inexpensive and generally
      safe diagnostic procedure in the management of thyroid nodules. Post-FNB local
      pain and minor haematomas are the most common complications, while serious
      complications seem to be rare. Given that use of FNB minimizes unnecessary
      surgery and subsequent operative morbidity and mortality as well as the fact that
      the majority of FNB complications resolve spontaneously, the overall safety of
      FNB is not questioned. However, awareness of the potential complications and
      careful estimation of the risk-benefit ratio in an individual basis may further
      decrease the low morbidity of FNB. In this systematic review we tried to collect
      and summarize all reported clinical complications following diagnostic thyroid
      FNB, aiming to make physicians aware of possible complications and to provide
      preventive measures to avoid them.

PMID- 19170716
TI  - Plasma monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory
      protein-1alpha are increased in patients with polycystic ovary syndrome (PCOS)
      and associated with adiposity, but unaffected by pioglitazone treatment.
AB  - OBJECTIVE: Hirsutism is most often caused by polycystic ovary syndrome (PCOS).
      PCOS patients are characterized by insulin resistance, abdominal obesity and low
      grade inflammation. Insulin sensitizing treatment reduces the inflammatory state,
      but the effect on serum levels of migration inhibitor factor (MIF), monocyte
      chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha
      have not been evaluated before in PCOS. RESEARCH DESIGN AND METHODS: Plasma
      chemokine levels (MCP-1, MIP-1alpha and MIF) were measured in two study designs.
      (i) 51 hirsute patients and 63 matched controls and (ii) 30 PCOS patients before
      and after randomized treatment with 30 mg pioglitazone/placebo for 16 weeks.
      Clinical evaluations and whole body DXA-scans were performed in all participants.
      RESULTS: Hirsute patients (n = 51) had significantly increased MCP-1 [121 (15
      950) vs. 81 (18-365) pg/ml; P < 0.05] and MIP-1alpha[179 (8-4202) vs. 103 (4
      1598) pg/ml; P < 0.05] than controls of matched body composition [geometric mean
      (-2SD to +2SD)]. In PCOS (n = 30), MCP-1, MIP-1alpha and MIF correlated
      positively with central fat mass. A BMI independent positive association was
      found between MIF and free testosterone (r = 0.49, P = 0.01) in PCOS.
      Pioglitazone treatment significantly improved insulin sensitivity without
      affecting testosterone, body composition, MCP-1, MIP-1alpha and MIF levels.
      CONCLUSIONS: Chemokine levels were significantly increased and showed close
      associations with measures of adiposity in PCOS patients, but were unchanged
      during insulin sensitizing treatment with pioglitazone. Our data suggests a fat
      mass independent association between testosterone and MIF levels in PCOS and the
      effect of anti-androgen treatment on chemokine levels needs to be examined.

PMID- 19170718
TI  - Toriello-Carey syndrome in a patient with a de novo balanced translocation
      [46,XY,t(2;14)(q33;q22)] interrupting SATB2.
AB  - Toriello-Carey syndrome (TCS; OMIM 217980) is a multiple congenital anomaly
      syndrome characterized by the common manifestations of corpus callosum agenesis,
      cardiac defects, cleft palate/Robin sequence, hypotonia, mental retardation,
      postnatal growth retardation and distinctive facial dysmorphology (including
      micrognathia, telecanthus, small nose and full cheeks). Both autosomal recessive
      and X-linked inheritance have been proposed, but chromosomal abnormalities
      involving disparate loci have also been detected in a small number of cases. We
      report a patient with classical features of TCS and an apparently balanced de
      novo translocation between chromosomes 2 and 14 [46,XY,t(2;14)(q33;q22)].
      Molecular characterization revealed direct interruption of the special AT-rich
      sequence-binding protein-2 (SATB2) gene at the 2q33.1 translocation breakpoint,
      while the 14q22.3 breakpoint was not intragenic. SATB2 mutation or deletion has
      been associated with both isolated and syndromic facial clefting; however, an
      association with TCS has not been reported. SATB2 functions broadly as a
      transcription regulator, and its expression patterns suggest an important role in
      craniofacial and central nervous system development, making it a plausible
      candidate gene for TCS.

PMID- 19170719
TI  - Influence of different operatory setups on implant survival rate: a retrospective
      clinical study.
AB  - BACKGROUND: Surgery performed under sterile operating conditions, as well as
      atraumatic surgery, has been stated to be among the most important requirements
      for successful osseointegration. However, there are few reports concerning the
      sterile surgical technique in association with implant placement, and the
      appropriate level of operatory setup is not fully known. PURPOSE: The purpose of
      this study was to analyze implant survival rate using a simplified surgical
      operatory setup compared with the use of the original Branemark System (Nobel
      Biocare AB, Goteborg, Sweden) protocol. MATERIALS AND METHODS: A total of 1,285
      consecutively treated patients were included in the study. Four thousand implants
      were placed during the period of 1985 to 2003. Group A (using the Branemark
      System protocol) comprised of 654 patients and 2,414 implants. Group B (using a
      simplified operatory setup) comprised of 631 patients and 1,586 implants. Healing
      was evaluated after 6 months of clinical function. Failure was defined as the
      removal of implants because of nonosseointegration. Statistic analysis was
      performed using t-test for paired data. The level of significance was set at 5%
      for comparison of data. RESULTS: No significant difference with regard to
      complications and implant survival rate was found in the study. CONCLUSION: The
      result from the present study suggests that a simplified operatory setup does not
      affect the survival rate of oral implant treatment.

PMID- 19170720
TI  - Changes in left ventricular ejection time and pulse transit time derived from
      finger photoplethysmogram and electrocardiogram during moderate haemorrhage.
AB  - OBJECTIVES: Early identification of haemorrhage is difficult when a bleeding site
      is not apparent. This study explored the potential use of the finger
      photoplethysmographic (PPG) waveform derived left ventricular ejection time
      (LVET(p)) and pulse transit time (PTT) for detecting blood loss, by using blood
      donation as a model of controlled mild to moderate haemorrhage. METHODS: This was
      a prospective, observational study carried out in a convenience sample of blood
      donors. LVET(p), PTT and R-R interval (RRi) were computed from simultaneous
      measurement of the electrocardiogram (ECG) and the finger infrared
      photoplethysmogram obtained from 43 healthy volunteers during blood donation. The
      blood donation process was divided into four stages: (i) Pre-donation (PRE), (ii)
      first half of donation (FIRST), (iii) second half of donation (SECOND), (iv) post
      donation (POST). RESULTS AND CONCLUSIONS: Shortening of LVET(p) from 303+/-2 to
      293+/-3 ms (mean+/-SEM; P<0.01) and prolongation of PTT from 177+/-3 to 186+/-4
      ms (P<0.01) were observed in 81% and 91% of subjects respectively when comparing
      PRE and POST. During blood donation, progressive blood loss produced falling
      trends in LVET(p) (P<0.01) and rising trends in PTT (P<0.01) in FIRST and SECOND,
      but a falling trend in RRi (P<0.01) was only observed in SECOND. Monitoring
      trends in timing variables derived from non-invasive ECG and finger PPG signals
      may facilitate detection of blood loss in the early phase.

PMID- 19170721
TI  - The validity of questionnaire-based assessment of psychopathology in children
      with epilepsy.

PMID- 19170722
TI  - Increases in muscle volume after plantarflexor strength training in children with
      spastic cerebral palsy.
AB  - Children with spastic cerebral palsy (CP) have small, weak muscles. However,
      change in muscle size due to resistance training in this group is unknown. We
      investigated the effect of plantarflexor strengthening on muscle volume, gait,
      and function in 13 ambulant children with spastic CP (seven males, six females;
      mean age 10 y 11 mo, SD 3 y 0 mo, range 6 y 11 mo-16 y 11 mo; eight with
      diplegia, five with hemiplegia; Gross Motor Function Classification System level
      I, six; level II, five; level III, two). Assessments were performed before
      training, 5 and 10 weeks into training, and at a 3-month follow-up. Medial and
      lateral gastrocnemius volumes were computed from three-dimensional ultrasound
      images. The number of unilateral heel raises able to be achieved on each side was
      assessed. Function was measured using three-dimensional gait analysis, the 'timed
      up and go' test, the Gillette Functional Assessment Questionnaire, and the
      Functional Mobility Scale. Training involved heel raises or Thera-Band
      resistance, 4 times a week for 10 weeks. Medial and lateral gastrocnemius volumes
      increased by 17 and 14% at week 5 (p=0.03, p=0.028). This increase was maintained
      at week 10 and follow-up (medial gastrocnemius p=0.001, p<0.001; lateral
      gastrocnemius p=0.006, p=0.007). Heel raises (mean number) increased by week 5
      (p=0.002). This was maintained at week 10 and follow-up (p<0.001; p<0.001). No
      significant change in measured function was observed. Muscle volume increased in
      response to training in children with spastic CP. The role of progressive
      strength training in maintaining long-term function is discussed.

PMID- 19170723
TI  - Young children's use of a visual aid: an experimental study of the effectiveness
      of training.
AB  - We report an experiment concerning the use of a stand magnifier by young children
      with visual impairments (21 males, 12 females; mean age 4y 8mo [SD 11mo]).
      Children had a normative developmental level and a visual acuity of 0.4 or less
      (< or =20/50 in Snellen's notation). To measure magnifier use objectively, we
      developed a task that closely resembled the dynamics of its real-life (pre
      reading) use. Children had to follow trails visually, from a start location to an
      unseen end location. This could only be done successfully and reliably by proper
      use of the magnifier. In addition to this, we analyzed the effect of specific
      training with the magnifier by using a repeated-measures (before and after
      training) matched-groups (with respect to age and near-visual acuity) design.
      Results established both the task's efficacy as an instrument for measuring
      magnifier use in young children and the effectiveness of the training.
      Improvement in task performance after training was found in both groups, except
      for the youngest children (<3y 6mo). On average, 1.8 times as many paths were
      followed in both groups after training (p=0.001). The without-magnifier training
      group became 2.5 times as good at finding the correct end location, whereas the
      with-magnifier training group became 4.3 times as good (p=0.05).

PMID- 19170724
TI  - Effect of nebivolol on blood oxygen transport indices and endothelial dysfunction
      in patients with arterial hypertension.
AB  - Endothelial dysfunction, which is characterized by impairment of nitric oxide
      (NO) bioavailability, plays an important role in the development of arterial
      hypertension. The L-arginine-NO pathway is closely related to oxygen transport to
      tissue. Endothelial dysfunction in patients with arterial hypertension can affect
      haemoglobin-oxygen affinity and tissue oxygen supply. Alterations in blood oxygen
      transport indices may play role in the pathogenesis of arterial hypertension. The
      aim of the present study was to investigate the effect of the beta-selective
      adrenoblocker nebilet (nebivolol) on blood oxygen transport indices and on
      endothelial dysfunction in patients with arterial hypertension. The study
      population included 52 patients with grade II and grade III arterial
      hypertension. The results of our studies indicate that endothelial dysfunction in
      hypertensive patients significantly changes blood oxygen indices. The endothelium
      can be involved in formation of these impairments because only NO synthesized in
      sufficient amounts can maintain normal blood flow and oxygen transport to
      tissues. Endothelial dysfunction impairs formation of different haemoglobin NO
      derivatives, that influence not only on the release of NO at different sites of
      the vascular bed, but also on haemoglobin-oxygen affinity, and accordingly, on
      optimal blood oxygenation in capillaries of pulmonary circulation and its
      deoxygenation in capillaries of systemic circulation. Treatment of hypertensive
      patients with nebivolol corrects the blood oxygen transport indices, stimulates
      NO production and improves endothelium-dependent dilatation. Normalization of
      blood oxygen transport indices may regulate the activity of the L-arginine-NO
      pathway. Thus, nebivolol may improve efficiency of the treatment of hypertension.

PMID- 19170725
TI  - Candidatus Desulfovibrio trichonymphae, a novel intracellular symbiont of the
      flagellate Trichonympha agilis in termite gut.
AB  - Rs-N31, a 16S rRNA phylotype affiliated with the genus Desulfovibrio, has
      frequently been detected from the gut of the wood-feeding termite Reticulitermes
      speratus. In this study, we designed a probe specifically targeting phylotype Rs
      N31 and performed fluorescence in situ hybridization to identify the
      corresponding cells. The signals were detected exclusively inside the cells of
      the flagellate Trichonympha agilis, which simultaneously harbours another
      intracellular bacterium belonging to the candidate phylum Termite Group 1 (TG1).
      The detected cells were coccoid or short rods and specifically localized in the
      cortical layer of mainly, the anterior part of the flagellate cell. Approximately
      1800 cells were contained in a single host cell, accounting for, in total, 2% of
      the whole prokaryotic gut microbiota. The genes dsrAB and apsA for sulfate
      reduction and a gene-encoding H(2)-uptake hydrogenase, both possessing a high
      sequence identity with those of known desulfovibrios, were obtained by polymerase
      chain reaction (PCR) from the host cells isolated using a micromanipulator, and
      their expression was verified by reverse-transcription PCR. Thus, we suggest that
      this endosymbiont acts as a sink for the hydrogen generated by both the
      flagellates and possibly TG1 symbionts. For this uncultured bacterium, we propose
      a novel species, 'Candidatus Desulfovibrio trichonymphae'.

PMID- 19170726
TI  - Methylmercury enters an aquatic food web through acidophilic microbial mats in
      Yellowstone National Park, Wyoming.
AB  - Microbial mats are a visible and abundant life form inhabiting the extreme
      environments in Yellowstone National Park (YNP), WY, USA. Little is known of
      their role in food webs that exist in the Park's geothermal habitats. Eukaryotic
      green algae associated with a phototrophic green/purple Zygogonium microbial mat
      community that inhabits low-temperature regions of acidic (pH approximately 3.0)
      thermal springs were found to serve as a food source for stratiomyid (Diptera:
      Stratiomyidae) larvae. Mercury in spring source water was taken up and
      concentrated by the mat biomass. Monomethylmercury compounds (MeHg(+)), while
      undetectable or near the detection limit (0.025 ng l(-1)) in the source water of
      the springs, was present at concentrations of 4-7 ng g(-1) dry weight of mat
      biomass. Detection of MeHg(+) in tracheal tissue of larvae grazing the mat
      suggests that MeHg(+) enters this geothermal food web through the phototrophic
      microbial mat community. The concentration of MeHg(+) was two to five times
      higher in larval tissue than mat biomass indicating MeHg(+) biomagnification
      occurred between primary producer and primary consumer trophic levels. The
      Zygogonium mat community and stratiomyid larvae may also play a role in the
      transfer of MeHg(+) to species in the food web whose range extends beyond a
      particular geothermal feature of YNP.

PMID- 19170727
TI  - HD-GYP domain proteins regulate biofilm formation and virulence in Pseudomonas
      aeruginosa.
AB  - HD-GYP is a protein domain involved in the hydrolysis of the bacterial second
      messenger cyclic-di-GMP. The genome of the human pathogen Pseudomonas aeruginosa
      PAO1 encodes two proteins (PA4108, PA4781) with an HD-GYP domain and a third
      protein, PA2572, which contains a domain with variant key residues (YN-GYP). Here
      we have investigated the role of these proteins in biofilm formation, virulence
      factor synthesis and virulence of P. aeruginosa. Mutation of PA4108 and PA4781
      led to an increase in the level of cyclic-di-GMP in P. aeruginosa, consistent
      with the predicted activity of the encoded proteins as cyclic-di-GMP
      phosphodiesterases. Mutation of both genes led to reduced swarming motility but
      had differing effects on production of the virulence factors pyocyanin, pyoverdin
      and ExoS. Mutation of PA2572 had no effect on cyclic-di-GMP levels and did not
      influence swarming motility. However, PA2572 had a negative influence on swarming
      that was cryptic and was revealed only after removal of an uncharacterized C
      terminal domain. Mutation of PA4108, PA4781 and PA2572 had distinct effects on
      biofilm formation and architecture of P. aeruginosa. All three proteins
      contributed to virulence of P. aeruginosa to larvae of the Greater Wax moth
      Galleria mellonella.

PMID- 19170729
TI  - Inferring the parameters of the neutral theory of biodiversity using phylogenetic
      information and implications for tropical forests.
AB  - We develop a statistical method to infer the parameters of Hubbell's neutral
      model of biodiversity using data on local species abundances and their
      phylogenetic relatedness. This method uses the approximate Bayesian computation
      (ABC) approach, where the data are summarized into a small number of informative
      summary statistics. We used three statistics: the number of species in the
      sample, Shannon H index of evenness and Shao and Sokal's B(1) index of
      phylogenetic tree imbalance. Our approach was found to outperform previous
      methods, illustrating the potential of ABC methods in ecology. Applying it to
      four large tropical forest tree data sets, the best-fit immigration rates m were
      found to be two orders of magnitude smaller and regional diversities theta larger
      than previously reported for the same data. This implies that neutral-compatible
      regional pools of tropical trees should extend over continental scales, and that
      m measures, in this context, mostly the frequency of long-distance dispersal
      events.

PMID- 19170730
TI  - Size of sampling unit strongly influences detection of seedling limitation in a
      wet tropical forest.
AB  - Seedling limitation could structure communities, but often is evaluated with
      sampling units that are orders of magnitude smaller than mature plants. We
      censused seedlings for 5.5 years in five 1 x 200-m transects in a wet Neotropical
      forest. For 106 common species (> or = 10 seedlings in a transect), we calculated
      prevalence (occurrence of > or = 1 newly emerged seedlings per sampling unit) at
      1 m(2) and at 1 m x mature crown diameter units by aggregating adjacent quadrats.
      For most species, prevalence was 2-25% at 1 m(2), but 20-92% at mature crown
      scales. Increased prevalence arose from broadly distributed seedlings within
      transects, with unoccupied segments generally shorter than crown diameters. At
      the landscape scale, 69% of 301 species were locally rare (< 10 seedlings) and
      only 16% were represented in all transects (maximally separated by 2.4 km).
      Nonetheless, for more common species, much lower estimates of seedling limitation
      at mature crown scales suggest weaker influence of seedling limitation on
      community dynamics than previously assumed.

PMID- 19170731
TI  - Informed dispersal, heterogeneity in animal dispersal syndromes and the dynamics
      of spatially structured populations.
AB  - There is accumulating evidence that individuals leave their natal area and select
      a breeding habitat non-randomly by relying upon information about their natal and
      future breeding environments. This variation in dispersal is not only based on
      external information (condition dependence) but also depends upon the internal
      state of individuals (phenotype dependence). As a consequence, not all dispersers
      are of the same quality or search for the same habitats. In addition, the
      individual's state is characterized by morphological, physiological or
      behavioural attributes that might themselves serve as a cue altering the habitat
      choice of conspecifics. These combined effects of internal and external
      information have the potential to generate complex movement patterns and could
      influence population dynamics and colonization processes. Here, we highlight
      three particular processes that link condition-dependent dispersal, phenotype
      dependent dispersal and habitat choice strategies: (1) the relationship between
      the cause of departure and the dispersers' phenotype; (2) the relationship
      between the cause of departure and the settlement behaviour and (3) the concept
      of informed dispersal, where individuals gather and transfer information before
      and during their movements through the landscape. We review the empirical
      evidence for these processes with a special emphasis on vertebrate and arthropod
      model systems, and present case studies that have quantified the impacts of these
      processes on spatially structured population dynamics. We also discuss recent
      literature providing strong evidence that individual variation in dispersal has
      an important impact on both reinforcement and colonization success and therefore
      must be taken into account when predicting ecological responses to global warming
      and habitat fragmentation.

PMID- 19170732
TI  - Vagus nerve stimulation for refractory epilepsy in children: More to VNS than
      seizure frequency reduction.
AB  - PURPOSE: Vagus nerve stimulation (VNS) is used increasingly as adjunctive therapy
      for refractory epilepsy. Studies of VNS in children report mainly seizure
      frequency reduction as a measure of efficacy and clinical details are often
      scanty. We report our experience with VNS in children with refractory epilepsy
      and emphasize the positive effects of VNS in terms of seizure severity. METHODS:
      We reviewed 26 consecutive children who had VNS with a minimum follow-up period
      of 18 months. We examined their clinical characteristics, seizure types, seizure
      frequency, epilepsy syndrome diagnosis, and response to VNS in terms of seizure
      frequency and seizure severity. RESULTS: Fifty-four percent of patients responded
      to VNS with >or=50% seizure frequency reduction. Patients with Lennox-Gastaut
      syndrome (LGS) and tonic seizures had a higher responder rate; 78% (seven of nine
      patients) (p < 0.01). Status epilepticus (SE) episodes were reduced or ceased in
      the four patients with recurrent SE. Seizure severity, duration, and recovery
      time decreased in all responders. Increased alertness was reported in all
      responders and three nonresponders. CONCLUSION: Decreased seizure severity,
      recovery time, abolition of daytime drop attacks, and reduced hospitalization due
      to SE improved patients' lives over and above the benefit from seizure frequency
      reduction.

PMID- 19170728
TI  - Transcriptional activity of paddy soil bacterial communities.
AB  - Bulk mRNA was used to explore the transcriptional activity of bacterial
      communities in oxic versus anoxic paddy soil. Two microbial cDNA libraries were
      constructed from composite samples using semi-randomly primed RT-PCR. cDNAs
      averaged 500-600 bp in length and were treated as expressed sequence tags (ESTs).
      Clustering analysis of 805 random cDNAs resulted in 179 and 155 different ESTs
      for the oxic and anoxic zones respectively. Using an E-value threshold of e(-10),
      a total of 218 different ESTs could be assigned by blastx, while 116 ESTs were
      predicted novel. Both the proportion and significance of the EST assignments
      increased with cDNA length. Taxonomic assignment was more powerful in
      discriminating between the aerobic and anaerobic bacterial communities than
      functional inference, as most ESTs in both oxygen zones were putative indicators
      of similar housekeeping functions, in particular ABC-type transporters. A few
      ESTs were putative indicators for community function in a biogeochemical context,
      such as beta-oxidation of long-chain fatty acids specifically in the oxic zone.
      Expressed sequence tags assigned to Alpha- and Betaproteobacteria were
      predominantly found in the oxic zone, while those affiliated with
      Deltaproteobacteria were more frequently detected in the anoxic zone. At the
      genus level, multiple assignments to Bradyrhizobium and Geobacter were unique to
      the oxic and anoxic zones respectively. The phylum-level affiliations of 93 16S
      rRNA sequences corresponded well with two taxonomically distinct EST patterns.
      Expressed sequence tags affiliated with Acidobacteria and Chloroflexi were
      frequently detected in both oxygen zones. In summary, the soil metatranscriptome
      is accessible for global analysis and such studies have great potential in
      elucidating the taxonomic and functional status of soil bacterial communities,
      but study significance depends on the number and length of cDNAs being randomly
      analysed.

PMID- 19170734
TI  - Association of subjective anxiety, depression, and sleep disturbance with quality
      of-life ratings in adults with epilepsy.
AB  - PURPOSE: To determine the relative contributions of subjective anxiety,
      depression, sleep disturbance, and seizure-related variables to quality-of-life
      scores in adults with epilepsy, and the interrelationships among these factors.
      METHODS: Consecutive adult patients with epilepsy attending neurology outpatient
      clinics were recruited. Patients completed the following scales: Hospital Anxiety
      and Depression Scale (HADS), Hamilton Anxiety Rating Scale, Medical Outcomes
      Study (MOS) Sleep Scale, Epworth Sleepiness Scale, and Quality of Life in
      Epilepsy Inventory-31 (QOLIE-31). Univariate and multivariate linear regression
      models were used to identify variables associated with QOLIE-31 overall score.
      Path analysis model was constructed to test for interrelations between the
      variables. RESULTS: Two hundred forty-seven patients completed the
      questionnaires. By multivariate analysis, in order of degree of contribution,
      HADS anxiety subscale score, MOS Sleep Scale Sleep Problems Index score, HADS
      depression subscale score, number of current antiepileptic drugs used, and
      seizure freedom in the past 4 weeks, significantly correlated with QOLIE-31
      overall score, accounting for 65.2% of the variance. Complex interrelationships
      were present between these factors. A general linear model to predict QOLIE-31
      overall score in the presence of these factors was constructed. CONCLUSION:
      Subjective anxiety, depression, and sleep disturbance exerted greater effect than
      short-term seizure control on quality of life scores of patients with epilepsy.
      These factors should be considered simultaneously when evaluating effects of
      treatment on quality of life.

PMID- 19170733
TI  - Single and repetitive paired-pulse suppression: a parametric analysis and
      assessment of usefulness in epilepsy research.
AB  - PURPOSE: The paired-pulse technique has been widely used as a convenient but
      indirect measure of "inhibition" in hippocampal circuits of normal and epileptic
      animals. Most investigators have used a single paired-pulse protocol, whereas
      others have utilized repetitive paired pulses. This study investigated which
      parameters influence results from paired-pulse tests, focusing on the repetitive
      paired-pulse technique; it aims to assess how this technique may be used in an
      unbiased and quantitative manner across animal preparations for comparisons of
      control and experimental epileptic animals. METHODS: The perforant path was
      stimulated while field potentials were recorded from the granule cell layer under
      isoflurane anesthesia. Paired-pulse suppression was analyzed as a function of
      stimulation intensity and interpulse interval and frequency. RESULTS: Paired
      pulse suppression was greater with increased stimulus intensity and decreased
      interpulse interval (20-100 ms). During repetitive protocols, stimulation
      frequencies <or=1.0 Hz produced paired-pulse suppression similar to single paired
      pulse responses, but caused more paired-pulse suppression between 1.0 and 4.0 Hz
      at all but the lowest intensities. The amplitude of the population spike produced
      by the conditioning pulse increased progressively during stimulation at higher
      frequencies (1.0-4.0 Hz). DISCUSSION: The single paired-pulse technique is highly
      dependent on stimulation parameters, as is the repetitive paired-pulse protocol,
      which is more variable. To generate reliable, consistent, and unbiased data in
      comparisons of control and experimental epileptic groups, all parameters should
      be specified and controlled across experiments. Paired-pulse suppression is
      susceptible to alterations in many mechanisms, and, therefore, represents a
      circuit response rather than an assay of gamma-aminobutyric acid (GABA)ergic
      inhibition in epilepsy research.

PMID- 19170735
TI  - Coexistence of Unverricht-Lundborg disease and congenital deafness: molecular
      resolution of a complex comorbidity.
AB  - PURPOSE: We report on genetic analysis of a complex condition in a Serbian family
      of four siblings, wherein two had progressive myoclonic epilepsy (PME) and
      congenital deafness (CD), one had isolated congenital deafness (ICD), and one was
      healthy. METHODS AND RESULTS: Molecular diagnosis performed by Southern blotting
      confirmed Unverricht-Lundborg disease in the available sibling with PME/CD. In
      the sibling with ICD (heterozygote for expansion mutation in CSTB) we
      demonstrated recombination event between the D21S2040 marker and the CSTB gene
      and identified c.207delC (p.T70Xfs) mutation in the fourth exon of the
      transmembrane protease, serine-3 (TMPRSS3) gene (maps in close proximity to
      CSTB), responsible for nonsyndromic deafness in the sibling with PME/CD as well.
      DISCUSSION: To the best of our knowledge this is the first genetic confirmation
      of the coexistence of these two mutations.

PMID- 19170736
TI  - Ictal vocalizations occur more often in temporal lobe epilepsy with dominant
      (left-sided) epileptogenic zone.
AB  - OBJECTIVE: To investigate the lateralization value of ictal vocalizations in
      temporal lobe epilepsy (TLE). METHODS: We reviewed video-recordings of 97
      patients who had undergone presurgical evaluation programs with video-EEG
      (electroencephalography)-recorded complex partial seizures (CPS) and high
      resolution magnetic resonance imaging (MRI). All patients had surgery due to TLE
      and became seizure-free. In 57 patients, determination of speech dominance was
      necessary by using Wada tests or functional MRI (fMRI). To reevaluate the
      archived seizures, we reviewed one to three consecutively recorded CPS of each
      patient. Altogether 223 archived seizures were analyzed. Ictal vocalization was
      considered to be present in a particular patient if it occurred in at least one
      of the recorded seizures. RESULTS: Ictal vocalizations occurred in 22 patients.
      They occurred in 37% of left-sided and in 11% of right-sided patients with TLE (p
      = 0.003). In patients with determined speech lateralization, ictal vocalizations
      occurred in 37% of the dominant and in 14% in patients with nondominant
      epileptogenic zone (p = 0.04). In patients with ictal vocalizations, epilepsy
      began at age 8.7 +/- 6, whereas in the remaining patients, epilepsy started at
      age 14.0 +/- 9 (p = 0.017). Logistic regression showed that both hemispheric
      dominance and age at onset were independently associated with pure ictal
      vocalization (PIV). CONCLUSIONS: Ictal vocalization is a frequent phenomenon,
      occurring in 23% of patients with TLE. It is more often associated with left
      sided and early onset TLE. Our results may improve the lateralization of the
      epileptogenic zone and suggest that nonspeech vocalizations in humans are related
      to the dominant (left-sided) hemisphere. Our study is a further argument that
      there are different subtypes of TLE depending on the age at onset.

PMID- 19170738
TI  - Ethical issues related to epilepsy care in the developing world.
AB  - There are three major issues of ethical concern related to epilepsy care in the
      developing world. First, is it ethical for a developing country to channel its
      limited resources from direct epilepsy care to research? The main considerations
      in addressing this question are the particular research questions to be addressed
      and whether such research will bring direct benefits to the local community.
      Second, in a country with limited resources, when does ignoring the high
      treatment gap become an ethical issue? This question is of particular concern
      when the community has enough resources to afford treatment for its poor, yet is
      not providing such care because of gross wastage and misallocation of the
      national resources. Third, do countries with plentiful resources have an ethical
      responsibility to help relieve the high epilepsy treatment gap of poor countries?
      Indeed, we believe that reasonable health care is a basic human right, and that
      human rights transcend national boundaries. Although health care is usually the
      responsibility of the nation-state, many modern states in the developing world
      are arbitrary creations of colonization. There is often a long process from the
      establishment of a political-legal state to a mature functional nation. During
      the long process of nation building, help from neighboring countries is often
      required.

PMID- 19170737
TI  - Clobazam in the treatment of Lennox-Gastaut syndrome.
AB  - PURPOSE: This randomized, double-blind, dose-ranging study evaluated safety and
      efficacy of clobazam (CLB) as adjunctive therapy for drop seizures in patients
      with Lennox-Gastaut syndrome (LGS). METHODS: Sixty-eight patients with LGS aged 2
      26 years were administered CLB (low dose = target 0.25 mg/kg/day; high dose =
      target 1.0 mg/kg/day). The study consisted of 4-week baseline, 3-week titration,
      and 4-week maintenance periods, followed by a 3-week taper or continuation in an
      open-label study. Seizure frequency was recorded in a diary by the
      parent/caregiver throughout the study. RESULTS: Weekly drop seizure rates were
      significantly reduced from baseline in both the high-dose and low-dose groups;
      the reduction was significantly greater in the high-dose group. A significantly
      greater proportion of patients in the high-dose group experienced reductions in
      drop seizures of >or=25%, >or=50%, and >or=75% compared to the low-dose group;
      more patients in the high-dose group experienced a 100% reduction, but the
      difference was not significant. Nondrop seizures were also reduced in a dose
      dependent manner. In both investigator and parent/caregiver global evaluations,
      patients in the high-dose group showed significantly greater improvements in
      overall symptoms compared to low-dose CLB. Adverse events were generally mild or
      moderate, and were similar between dose groups. Five serious adverse events were
      reported in four patients, but in no case was CLB discontinued. CONCLUSIONS:
      Clobazam was well tolerated and reduced drop seizure rates; high-dose CLB was
      more effective than low-dose CLB. Other seizure types were also reduced.

PMID- 19170739
TI  - Trauma, stress, and preconscious threat processing in patients with psychogenic
      nonepileptic seizures.
AB  - PURPOSE: Psychogenic nonepileptic seizures (PNES) have long been considered as
      paroxysmal dissociative symptoms characterized by an alteration of attentional
      functions caused by severe stress or trauma. Although interpersonal trauma is
      common in PNES, the proposed relation between trauma and attentional functions
      remains under explored. We examined the attentional processing of social threat
      in PNES in relation to interpersonal trauma and acute psychological stress.
      METHODS: A masked emotional Stroop test, comparing color-naming latencies for
      backwardly masked angry, neutral, and happy faces, was administered to 19
      unmedicated patients with PNES and 20 matched healthy controls, at baseline and
      in a stress condition. Stress was induced by means of the Trier Social Stress
      Test and physiologic stress parameters, such as heart rate variability (HRV) and
      cortisol, were measured throughout the experiment. RESULTS: No group differences
      related to the acute stress induction were found. Compared to controls, however,
      patients displayed a positive attentional bias for masked angry faces at
      baseline, which was correlated to self-reported sexual trauma. Moreover, patients
      showed lower HRV at baseline and during recovery. DISCUSSION: These findings are
      suggestive of a state of hypervigilance in patients with PNES. The relation with
      self-reported trauma, moreover, offers the first evidence linking psychological
      risk factors to altered information processing in PNES.

PMID- 19170740
TI  - Cause of death in patients with dementia disorders.
AB  - BACKGROUND: Investigations on cause of death may provide valuable information
      about life expectancy and on conditions of terminal dementia care, which perhaps
      can be ameliorated. METHODS: The autopsy reports were studied on all patients (n
      = 524; 55.3% females; median age 80 years) with a clinically and
      neuropathologically diagnosed dementia disorder who underwent a complete autopsy
      at the University Hospital in Lund, Sweden, during 1974-2004. RESULTS: The two
      most common causes of death were bronchopneumonia (38.4%) and ischaemic heart
      disease (23.1%), whilst neoplastic diseases were uncommon (3.8%). In a general
      population of elderly studied for comparison, bronchopneumonia accounted for
      2.8%, ischaemic heart disease for 22.0%, and neoplasm for 21.3% of the deaths.
      Amongst the demented patients, circulatory and respiratory system diseases were
      the causes of death in 23.2% and 55.5% of the Alzheimer patients, respectively,
      whilst the corresponding figures were 54.8% and 33.1% for the patients with
      vascular dementia. CONCLUSIONS: In patients with dementia, pneumonia as the
      immediate cause of death may reflect a terminal stage in which patient care and
      feeding is difficult to manage well. Knowledge about what actually causes death
      is of value in the terminal care of patients with dementia disorders.

PMID- 19170743
TI  - Clinical features of convulsive status epilepticus: a study of 220 cases in
      western China.
AB  - BACKGROUND AND PURPOSE: Convulsive status epilepticus (CSE) is the most common
      and life-threatening form of status epilepticus (SE). The aim of this study was
      to describe the clinical features of CSE in western China. METHODS: Convulsive
      status epilepticus patients hospitalized from January 1996 to October 2007 were
      prospectively observed. Logistic regression was used to identify predictors of
      prognosis. RESULTS: The average age of CSE patients (n = 220) was 37.5 years (SD
      20.31), 50% of the patients had a history of epilepsy. The primary cause of CSE
      was central nervous system infection (32.7%), followed by discontinuation or
      reduction of antiepileptic drugs (AEDs; 15.5%). The median duration of CSE was 5
      h and median duration of seizures before treatment was 2 h; both were longer in
      rural patients than in urban patients (P < 0.05). The fatality rate on discharge
      was 15.9%. Logistic regression analysis showed the duration of CSE [odds ratio
      (OR) 1.05, 95% confidence interval (CI) 1.03-1.07], a history of epilepsy (OR
      0.35, 95% CI 0.14-0.89), and respiratory depression (OR 5.96, 95% CI 2.49-14.24)
      were independent predictors of CSE prognosis. DISCUSSION: Central nervous system
      infection and AEDs withdrawal in epilepsy patients were the most important causes
      of CSE. There is a large gap between antiepileptic therapy in China and European
      Status Epilepticus guidelines.

PMID- 19170744
TI  - Age of puberty and the risk of multiple sclerosis: a population based study.
AB  - BACKGROUND AND PURPOSE: Genetic and environmental factors have important roles in
      multiple sclerosis (MS) susceptibility. Given a potential role for sex hormones
      in MS, we have investigated whether or not the age of puberty influences the risk
      of developing MS in a population-based cohort. METHODS: We identified 5493 MS
      index cases and 1759 spousal controls with age of puberty information from the
      Canadian Collaborative Project on Genetic Susceptibility to MS. Age of puberty
      was compared between index cases and controls, and any effect of age of puberty
      on the age of onset of MS was also investigated. RESULTS: There were no
      significant differences between male index cases and controls with respect to age
      of puberty, P = 0.70. However, a significant difference was observed between
      female index cases and female controls, with average age of puberty being 12.4
      and 12.6 years respectively, P = 0.00017, providing a relative risk decrease of
      0.9 per year increase of age of puberty. There was no effect of the age of
      puberty on the age of MS onset in either sex. CONCLUSIONS: Earlier age at
      menarche increases the risk of MS in women. Whether this association is a
      surrogate for a disease causative factor or directly involved in MS disease
      aetiology needs to be uncovered.

PMID- 19170745
TI  - Population-based case-control study of morale in Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is associated with cognitive, psychiatric,
      and motor features. Each could contribute to a poor sense of well-being and low
      morale. A systematic study of morale in community-dwelling PD cases has not been
      performed. METHODS: A total of 52 PD cases and 260 matched controls from three
      Spanish communities were assessed using the Philadelphia Geriatric Center Morale
      Scale (PGCMS) (range = 0[low morale]-17). The PGCMS includes three dimensions of
      psychological well-being: agitation, lonely dissatisfaction, and attitude toward
      own aging. RESULTS: The PGCMS score was lower in PD cases than controls (8.71 +/-
      3.64 vs. 11.03 +/- 2.77, P < 0.001), as were the agitation subscore (3.36 +/-
      1.91 vs. 4.07 +/- 1.59, P < 0.05), lonely dissatisfaction subscore (3.48 +/- 1.36
      vs. 4.11 +/- 1.12, P < 0.01), and attitude toward own aging subscore (1.86 +/-
      1.37 vs. 2.85 +/- 1.13, P < 0.001). In a linear regression analysis that adjusted
      for depressive symptoms and other covariates, PD cases had a lower PGCMS score
      than controls (P < 0.001). CONCLUSIONS: Morale was significantly lower in
      community-dwelling PD cases than matched controls. The detection and possible
      treatment of this problem may improve the psychological well-being of patients
      with this disease.

PMID- 19170747
TI  - Disrupted sleep and circadian patterns in frontotemporal dementia.
AB  - BACKGROUND: A study of the pattern of Sleep/Wake disturbance in frontotemporal
      dementia (FTD). METHODS: Sleep diaries and prolonged actigraphy were used to
      record the activity, sleep and wake of 13 patients with a clinical diagnosis of
      FTD. These were compared with diaries and actigraphy from normal age/sex matched
      controls and also to a population with probable Alzheimer's disease (AD).
      RESULTS: There was significant sleep/wake disturbance in FTD. This occurred
      throughout the course of the illness and the nature of the sleep disturbance was
      different to patients with AD. FTD subjects showed increased nocturnal activity
      and decreased morning activity compared with controls, suggesting possible phase
      delay. Sleep diary data confirmed decreased sleep efficiency and decreased total
      sleep in all FTD patients. CONCLUSIONS: We describe significant sleep disturbance
      in non-institutionalized patients with FTD and suggest that early sleep
      disturbance may help differentiate between FTD and AD.

PMID- 19170748
TI  - Spinal cord sarcoidosis: report of seven cases.
AB  - BACKGROUND: Spinal cord involvement in sarcoidosis is rare, occurring in <1% of
      patients with sarcoidosis. METHODS: We report seven cases of spinal cord
      sarcoidosis, seen in two French hospitals over a 13-year period. Presentation of
      disease, methods of diagnosis and response to treatment, with quantification
      according to the reduction of the modified Rankin scale (MRS), were noted.
      RESULTS: Six patients presented insidious paresthesias or weakness and one a
      sudden paraplegia. Average MRS at diagnosis was to 2. Spine MRI showed one or
      several intramedullary lesions in all cases. Diagnosis was confirmed by extra
      neural tissue biopsies in all cases, including mediastinoscopy (two patients),
      coelioscopy (one patient), bronchoscopy (one patient), salivary gland biopsy (one
      patient) and skin biopsy (two patients). The average follow-up for the group was
      49.4 months. All patients responded to corticosteroid therapy with a median
      reduction of MRS of one point. Five patients received immunosuppressive therapy:
      cyclophosphamide (two patients), methotrexate (two patients), azathioprine (one
      patient), mycophenolate mofetyl (one patient), with an inconstant benefit.
      Patients who received cyclophosphamide presented severe fungaemia. CONCLUSION:
      Based on our study and literature analysis, we propose an algorithm for treatment
      of spinal cord sarcoidosis.

PMID- 19170749
TI  - Late-onset vanishing white matter disease with compound heterozygous EIF2B5 gene
      mutations.

PMID- 19170750
TI  - Intravascular lymphoma presenting with neurological signs but diagnosed by
      prostate biopsy: suspicion as a key to early diagnosis.

PMID- 19170752
TI  - Identification, antifungal susceptibility and scanning electron microscopy of a
      keratinolytic strain of Rhodotorula mucilaginosa: a primary causative agent of
      onychomycosis.
AB  - Onychomycosis is a dermatological problem of high prevalence that mainly affects
      the hallux toenail. Onychomycosis caused by the yeast Rhodotorula mucilaginosa
      was identified using colony morphology, light microscopy, urease and carbohydrate
      metabolism in a 57-year-old immunocompetent patient from Rio de Janeiro, Brazil.
      High-resolution scanning electron microscopy of nail fragments, processed by a
      noncoating method, led to the observation with fine detail of the structures of
      both nail and fungus involved in the infection. Yeasts were mainly found inside
      grooves in the nail. Budding yeasts presented a spiral pattern of growth and
      blastoconidia were found in the nail groove region. Keratinase assays and keratin
      enzymography revealed that this isolate was highly capable of degrading keratin.
      Antifungal susceptibility tests showed that the fungus was susceptible to low
      concentrations of amphotericin B and 5-flucytosine and resistant to high
      concentrations of fluconazole, itraconazole, voriconazole and terbinafine. These
      findings showed data for the first time concerning the interaction of R.
      mucilaginosa in toenail infection and suggest that this emerging yeast should
      also be considered an opportunistic primary causative agent of onychomycosis.

PMID- 19170751
TI  - Sodium/bicarbonate cotransporter NBCn1/slc4a7 increases cytotoxicity in magnesium
      depletion in primary cultures of hippocampal neurons.
AB  - Growing evidence suggests that pharmacological inhibition of Na/H exchange and
      Na/HCO(3) transport provides protection against damage or injury in cardiac
      ischemia. In this study, we examined the contribution of the sodium/bicarbonate
      cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of
      rats. In neurons exposed to extracellular pH (pH(o)) ranging from 6.2 to 8.3,
      NBCn1 protein expression increased by fivefold at pH < 6.5 compared to the
      expression at pH(o) 7.4. At pH(o) 6.5, the intracellular pH of neurons was
      approximately 1 unit lower than that at pH 7.4. Immunochemistry showed a marked
      increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma
      as well as in dendrites, at pH(o) 6.5. NBCn1 expression also increased by 40% in
      a prolonged Mg(2+)-free incubation at normal pH(o). Knockdown of NBCn1 in neurons
      had negligible effect on cell viability. The effect of NBCn1 knockdown on
      cytotoxicity was then determined by exposing neurons to 0.5 mm glutamate for 10
      min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to
      normal incubation (pH(o) 7.2 for 6 h) after glutamate exposure, acidic incubation
      (pH(o) 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for
      NBCn1-knockdown neurons. Thus, both controls and knockdown neurons showed acidic
      protection from cytotoxicity. However, in Mg(2+)-free incubation after glutamate
      exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation
      was unaffected by acidic preincubation before glutamate exposure. We conclude
      that NBCn1 has a dynamic upregulation in low pH(o) and Mg(2+) depletion. NBCn1 is
      not required for acidic protection, but increases cytotoxicity in Mg(2+)-free
      conditions.

PMID- 19170753
TI  - Chlamydia trachomatis: identification of susceptibility markers for ocular and
      sexually transmitted infection by immunogenetics.
AB  - The aim of this review is to present a concise overview of all data available on
      the immunogenetics of Chlamydia trachomatis infections, both sexually transmitted
      urogenital and ocular infections. Currently, candidate gene approaches are used
      to identify genes related to the susceptibility to and severity of C. trachomatis
      infections. The main focus in the review will be on data obtained by the study of
      human cohorts.

PMID- 19170754
TI  - Genetic complexity of absence seizures in substrains of C3H mice.
AB  - Absence epilepsy is a common form of idiopathic generalized epilepsy whose
      etiology is poorly understood because of genetic and phenotypic heterogeneity.
      The inbred mouse strain C3H/He exhibits spontaneous absence seizures
      characterized by spike and wave discharges (SWD) on the electroencephalogram
      concomitant with behavioral arrest. Previous studies using the C3H/HeJ (HeJ)
      substrain identified a mutation in the Gria4 gene as a major susceptibility
      locus. In the present study, we found that two closely related substrains
      C3H/HeOuJ (OuJ) and C3H/HeSnJ, which have a similar SWD incidence as HeJ, do not
      contain the Gria4 mutation. Further analysis of backcross mice segregating OuJ
      and C57BL/6J alleles shows that, unlike the HeJ substrain, OuJ does not have a
      major locus for SWD but has suggestive loci at best that would explain only a
      fraction of the phenotypic variance. These results illustrate how the genetic
      etiology of a common neurological disorder can differ between substrains with
      similar phenotypes. We infer that all C3H strains are sensitized to SWD and that
      additional mutations affecting SWD arose or were fixed independently in the years
      since the substrains diverged.

PMID- 19170755
TI  - Haploinsufficiency of glutamine synthetase increases susceptibility to
      experimental febrile seizures.
AB  - Glutamine synthetase (GS) is a pivotal glial enzyme in the glutamate-glutamine
      cycle. GS is important in maintaining low extracellular glutamate concentrations
      and is downregulated in the hippocampus of temporal lobe epilepsy patients with
      mesial-temporal sclerosis, an epilepsy syndrome that is frequently associated
      with early life febrile seizures (FS). Human congenital loss of GS activity has
      been shown to result in brain malformations, seizures and death within days after
      birth. Recently, we showed that GS knockout mice die during embryonic development
      and that haploinsufficient GS mice have no obvious abnormalities or behavioral
      seizures. In the present study, we investigated whether reduced
      expression/activity of GS in haploinsufficient GS mice increased the
      susceptibility to experimentally induced FS. FS were elicited by warm-air-induced
      hyperthermia in 14-day-old mice and resulted in seizures in most animals. FS
      susceptibility was measured as latencies to four behavioral FS characteristics.
      Our phenotypic data show that haploinsufficient mice are more susceptible to
      experimentally induced FS (P < 0.005) than littermate controls. Haploinsufficient
      animals did not differ from controls in hippocampal amino acid content, structure
      (Nissl and calbindin), glial properties (glial fibrillary acidic protein and
      vimentin) or expression of other components of the glutamate-glutamine cycle
      (excitatory amino acid transporter-2 and vesicular glutamate transporter-1).
      Thus, we identified GS as a FS susceptibility gene. GS activity-disrupting
      mutations have been described in the human population, but heterozygote mutations
      were not clearly associated with seizures or epilepsy. Our results indicate that
      individuals with reduced GS activity may have reduced FS seizure thresholds.
      Genetic association studies will be required to test this hypothesis.

PMID- 19170756
TI  - SAP-1 is a microvillus-specific protein tyrosine phosphatase that modulates
      intestinal tumorigenesis.
AB  - SAP-1 (PTPRH) is a receptor-type protein tyrosine phosphatase (RPTP) with a
      single catalytic domain in its cytoplasmic region and fibronectin type III-like
      domains in its extracellular region. The cellular localization and biological
      functions of this RPTP have remained unknown, however. We now show that mouse SAP
      1 mRNA is largely restricted to the gastrointestinal tract and that SAP-1 protein
      localizes to the microvilli of the brush border in gastrointestinal epithelial
      cells. The expression of SAP-1 in mouse intestine is minimal during embryonic
      development but increases markedly after birth. SAP-1-deficient mice manifested
      no marked changes in morphology of the intestinal epithelium. In contrast, SAP-1
      ablation inhibited tumorigenesis in mice with a heterozygous mutation of the
      adenomatous polyposis coli gene. These results thus suggest that SAP-1 is a
      microvillus-specific RPTP that regulates intestinal tumorigenesis.

PMID- 19170757
TI  - Initiator titration complex formed at datA with the aid of IHF regulates
      replication timing in Escherichia coli.
AB  - The initiation of replication in Escherichia coli is negatively controlled by a
      mechanism referred to as 'initiator titration', a process by which the initiator
      protein, DnaA, is titrated to newly replicated binding sequences on the
      chromosome to reduce the initiation potential for replication. Initiator
      titration occurs predominantly at the datA locus that binds exceptionally large
      amounts of DnaA molecules to prevent aberrant initiations. We found that this was
      enabled by integration host factor (IHF). Within datA, there is a consensus IHF
      recognition sequence between the two DnaA recognition sequences (DnaA boxes)
      essential for its function. Binding of IHF to this site was demonstrated both in
      vitro and in vivo. Disruption of the core sequence in the consensus of the IHF
      binding resulted in increased origin concentration as observed in Delta datA
      cells. Furthermore, the number of DnaA molecules bound to datA was reduced in
      cells carrying a disruption in the IHF-binding core sequence. The IHF-binding
      site and the essential DnaA boxes had to be located at a proper distance and
      orientation to maintain the accurate initiation timing. Therefore, IHF is a
      unique element in the control of replication initiation that acts negatively at
      datA, while known to act as a positive regulator at oriC.

PMID- 19170758
TI  - Nucleo-cytoplasmic shuttling of protein arginine methyltransferase 1 (PRMT1)
      requires enzymatic activity.
AB  - Methylation of arginine residues is a widespread post-translational modification
      of proteins catalyzed by a family of protein arginine methyltransferases (PRMT),
      of which PRMT1 is the predominant member in human cells. We have previously
      described the localization and mobility of PRMT1 in live cells, and found that it
      shuttles between the nucleus and the cytoplasm depending on the methylation
      status of substrate proteins. Recently, amino-terminal splicing isoforms of PRMT1
      were shown to differ significantly in intracellular localization, the most
      interesting being splice variant 2 that carries a nuclear export signal in its
      amino terminus, and is expressed in increased levels in breast cancer cells. We
      show here that enzymatic activity is required for nucleo-cytoplasmic shuttling of
      PRMT1v2, as a catalytically inactive mutant highly accumulates in the nucleus and
      displays altered intranuclear mobility as determined by fluorescence recovery
      after photobleaching experiments. Our results indicate that nuclear export of
      PRMT1v2 is dominant over activity-independent nuclear import, but can only occur
      after activity-dependent release of the enzyme from substrates, suggesting that
      shuttling of the enzyme provides a dynamic mechanism for the regulation of
      substrate methylation.

PMID- 19170759
TI  - Identification of a novel REV1-interacting motif necessary for DNA polymerase
      kappa function.
AB  - When a replicative DNA polymerase (Pol) is stalled by damaged DNA, a "polymerase
      switch" recruits specialized translesion synthesis (TLS) DNA polymerase(s) to
      sites of damage. Mammalian cells have several TLS DNA polymerases, including the
      four Y-family enzymes (Poleta, Poliota, Polkappa and REV1) that share multiple
      primary sequence motifs, but show preferential bypass of different DNA lesions.
      REV1 interacts with Poleta, Poliota, and Polkappa and therefore appears to play a
      central role during TLS in vivo. Here we have investigated the molecular basis
      for interactions between REV1 and Polkappa. We have identified novel REV1
      interacting regions (RIRs) present in Polkappa, Poliota and Poleta. Within the
      RIRs, the presence of two consecutive phenylalanines (FF) is essential for REV1
      binding. The consensus sequence for REV1-binding is denoted by x-x-x-F-F-y-y-y-y
      (x, no specific residue and y, no specific residue but not proline). Our results
      identify structural requirements that are necessary for FF-flanking residues to
      confer interactions with REV1. A Polkappa mutant lacking REV1-binding activity
      did not complement the genotoxin-sensitivity of Polk-null mouse embryonic
      fibroblast cells, thereby demonstrating that the REV1-interaction is essential
      for Polkappa function in vivo.

PMID- 19170760
TI  - hnRNP K interacts with RNA binding motif protein 42 and functions in the
      maintenance of cellular ATP level during stress conditions.
AB  - Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a conserved RNA-binding
      protein that is involved in multiple processes of gene expression, including
      chromatin remodeling, transcription, RNA splicing, mRNA stability and
      translation, together with diverse groups of molecular partners. Here we
      identified a previously uncharacterized protein RNA binding motif protein 42
      (RBM42) as hnRNP K-binding protein. RBM42 directly bound to hnRNP K in vivo and
      in vitro. RBM42 also directly bound to the 3' untranslated region of p21 mRNA,
      one of the target mRNAs for hnRNP K. RBM42 predominantly localized within the
      nucleus and co-localized with hnRNP K there. When cells were treated with agents,
      puromycin, sorbitol or arsenite, which induced the formation of stress granules
      (SGs), cytoplasmic aggregates of stalled translational pre-initiation complexes,
      both hnRNP K and RBM42 localized at SGs. Depletion of hnRNP K by RNA interference
      decreased cellular ATP level following release from stress conditions.
      Simultaneous depletion of RBM42 with hnRNP K enhanced the effect of the hnRNP K
      depletion. Our results indicate that hnRNP K and RBM42 are components of SGs and
      suggest that hnRNP K and RBM42 have a role in the maintenance of cellular ATP
      level in the stress conditions possibly through protecting their target mRNAs.

PMID- 19170761
TI  - Abnormal red body coloration of the silkworm, Bombyx mori, is caused by a
      mutation in a novel kynureninase.
AB  - Larvae of the body color mutant red blood (rb) of the silkworm, Bombyx mori,
      display reddish skin whose hemolymph becomes red in air, whereas hemolymphs of
      normal strains become black during melanization. The irregular coloring was
      assumed to result from an abnormal accumulation of 3-hydroxykynurenine. However,
      the gene responsible for the rb phenotype is not yet known. Here, we provide
      evidence that the rb gene corresponds to a novel bacterial-type kynureninase
      gene, BmKynu. Kynureninase (KYNU) hydrolyzes kynurenine and 3-hydroxykynurenine
      to anthranilic acid and 3-hydroxyanthranilic acid, respectively. KYNU has been
      identified in microorganisms and animals but not in insects. Therefore, BmKynu is
      the first KYNU gene observed in insects. Our results clearly showed that a point
      mutation (T102I) in BmKYNU of the rb strain led to a marked decrease in KYNU
      activity, presumably resulting in abnormal accumulation of 3-hydroxykynurenine.
      Additionally, linkage analysis indicated that no recombination between rb and
      BmKynu was detected. We conclude that T102I in BmKYNU causes the red body
      coloration in the rb strain. Our study proves that B. mori has a unique side
      branch in the kynurenine pathway, distinctly different from other insects.

PMID- 19170762
TI  - Bone morphogenetic protein-2 enhances Wnt/beta-catenin signaling-induced
      osteoprotegerin expression.
AB  - Wnt/beta-catenin signaling plays an important role in the developing skeletal
      system. Our previous studies demonstrated that Wnt/beta-catenin signaling
      inhibits the ability of bone morphogenetic protein (BMP)-2 to suppress myotube
      formation in the multipotent mesenchymal cell line C2C12 and that this inhibition
      is mediated by Id1. In this study, we examined the role of intracellular
      signaling by Wnt/beta-catenin and BMP-2 in regulating the expression of
      osteoprotegerin (OPG) and of the receptor activator of NFkappaB ligand (RANKL).
      OPG expression was induced by Wnt/beta-catenin signaling in C2C12 cells and
      osteoblastic MC3T3-E1 cells. Silencing of glycogen synthase kinase-3beta also
      increased OPG expression. In contrast, R expression was suppressed by Wnt/beta
      catenin signaling. In a transfection assay, beta-catenin induced the activity of
      a reporter gene, a 1.5 kb fragment of the 5'-flanking region of the OPG gene.
      Deletion and mutation analysis revealed that Wnt/beta-catenin signaling regulates
      transcription of OPG via a promoter region containing two Wnt/beta-catenin
      responsive sites. BMP-2 enhanced Wnt/beta-catenin-dependent transcriptional
      activation of the OPG promoter. In response to BMP-2 stimulation, Smad 1 and 4
      interacted with Wnt/beta-catenin responsive sites. These results show that the
      regulation of OPG expression is mediated through two transcription pathways that
      involve the OPG promoter.

PMID- 19170764
TI  - Crystal structure of the Bach1 BTB domain and its regulation of homodimerization.
AB  - The BTB/POZ domain is known as a protein-protein interaction motif that mediates
      homodimer and higher order self-associations. Proteins containing the BTB domain
      exist throughout eukaryotes; however, there is little information about the
      mechanism that determines the oligomeric state of the BTB domain. To address this
      question, we have determined the X-ray structure of the mouse Bach1 BTB domain.
      The present structure is similar to the previously determined BTB domain folds,
      including the human Bach1 BTB domain; however, distinct structural features are
      present, such as a novel homodimer interaction surface. The homodimer formation
      was found to involve a novel hydrogen bond network and interactions between
      hydrophobic surfaces of the kinked N-terminus (N-hook) and the partner's C
      terminal residues. The deletion of the N-hook resulted in the conversion of the
      homodimer into a monomer in solution, indicating that the N-hook promotes the
      homodimerization of the mBach1 BTB domain. We have also found that the BTB domain
      of Bach2, a protein highly related to Bach1, is present as a monomer due to a
      short peptide insertion at the N-hook. These results represent the first example
      of the key modulatory element of BTB domain homodimerization.

PMID- 19170763
TI  - Proteomic and targeted analytical identification of BXDC1 and EBNA1BP2 as dynamic
      scaffold proteins in the nucleolus.
AB  - The nuclear matrix has classically been assumed to be a solid structure
      coherently aligning nuclear components, but its real nature remains obscure. We
      separated the proteins in a ribonucleoprotein-containing nuclear matrix fraction
      of HeLa cells by reversed-phase HPLC followed by SDS-PAGE, and identified 83
      proteins through peptide mass fingerprint (PMF) analysis. Many nucleolar
      proteins, classical nuclear matrix proteins, RNA binding proteins, cytoskeletal
      proteins and five uncharacterized proteins were identified in this fraction. Four
      of the latter proteins were localized to the cell nucleus, BXDC1 and EBNA1BP2
      being especially localized to the nucleolus. Fluorescence recovery after
      photobleaching and RNAi knockdown analyses suggested that BXDC1 and EBNA1BP2
      function in a dynamic scaffold for ribosome biogenesis.

PMID- 19170765
TI  - AMP-activated protein kinase phosphorylates glutamine : fructose-6-phosphate
      amidotransferase 1 at Ser243 to modulate its enzymatic activity.
AB  - Glutamine : fructose-6-phosphate amidotransferase 1 (GFAT1) was identified as a
      protein phosphorylated in glucose-deprived cells by immunoprecipitation using the
      anti-phospho Akt substrates (PAS) antibody, which recognizes the phosphorylation
      motif site by AMP-activated protein kinase (AMPK), followed by mass
      fingerprinting analysis. Glucose depletion-induced phosphorylation of endogenous
      GFAT was potentiated by 2-deoxyglucose (2-DG), an AMPK activator, and the 2-DG
      stimulated phosphorylation of FLAG-tagged GFAT1 in transfected cells was
      suppressed by Compound C, an AMPK inhibitor. The 2-DG induced phosphorylation of
      GFAT1 was attenuated by the introduction of the kinase-negative mutant of AMPK,
      and the phosphorylation was observed in the cells expressing the constitutively
      active mutant of AMPK even in the absence of 2-DG. Subsequent analysis revealed
      that the PAS antibody recognized GFAT1 phosphorylated at Ser243, which is
      conserved among different species. The assay of the GFAT enzymatic activity in
      the cell lysates indicated that the 2-DG-treatment inhibited the enzymatic
      activity, and Compound C-preincubation partially prevented the 2-DG-induced
      decrease of the activity. Furthermore, the mutant replacing Ser243 by alanine
      partially prevented the decrease of GFAT activity by 2-DG treatment. These
      results indicate that the phosphorylation of GFAT1 at Ser243 by AMPK has an
      important role in the regulation of the GFAT1 enzymatic activity.

PMID- 19170766
TI  - Retroendocytosis pathway of ABCA1/apoA-I contributes to HDL formation.
AB  - ATP-binding cassette protein A1 (ABCA1) mediates transfer of cellular free
      cholesterol and phospholipids to apolipoprotein A-I (apoA-I), an extracellular
      acceptor in plasma, to form high-density lipoprotein (HDL). It is currently
      unknown to what extent ABCA1 endocytosis and recycling contribute to the HDL
      formation. To address this issue, we expressed human ABCA1 constructs with either
      an extracellular HA tag or an intracellular GFP tag in cells, and used this
      system to characterize endocytosis and recycling of ABCA1 and apoA-I. Under basal
      conditions, ABCA1 and apoA-I are endocytosed via a clathrin- and Rab5-mediated
      pathway and recycled rapidly back to the cell surface, at least in part via a
      Rab4-mediated route; approximately 30% of the endocytosed ABCA1 is recycled back
      to the cell surface. When receptor-mediated endocytosis is inhibited, the level
      of ABCA1 at the cell surface increases and apoA-I internalization is blocked.
      Under these conditions, apoA-I mediated cholesterol efflux from cells that have
      accumulated lipoprotein-derived cholesterol is decreased, whereas efflux from
      cells without excess cholesterol is increased. These results suggest that the
      retroendocytosis pathway of ABCA1/apoA-I contributes to HDL formation when excess
      lipoprotein-derived cholesterol has accumulated in cells.

PMID- 19170767
TI  - O-Mannosylation is required for the solubilization of heterologously expressed
      human beta-amyloid precursor protein in Saccharomyces cerevisiae.
AB  - In an attempt to express human beta-amyloid precursor protein (APP) in yeast, we
      fortuitously found that this protein is only O-glycosylated in yeast. APP was
      effectively expressed in yeast, processed by yeast alpha-secretases, members of
      the Yapsin family, to produce N-terminal (sAPPalpha) and C-terminal (CTFalpha)
      domains, when its signal sequence was replaced by that of the yeast alpha-mating
      factor. APP is known to acquire N- and O-glycosylation through the endoplasmic
      reticulum (ER) and the Golgi apparatus and is transported to the plasma membrane
      in mammalian cells. In spite of the presence of canonical N-glycosylation
      consensus sequences, APP was not N-glycosylated in the yeast system. Pulse-chase
      experiments demonstrated that APP received only O-mannosylation in yeast.
      Examination of yeast pmt mutants, which are defective in the initiation of O
      mannosylation in the ER, revealed that Pmt4p is most responsible for the
      oligosaccharide modification of APP. Maturation of APP was slowed down and
      aggregated forms of APP were observed by sucrose density gradient fractionation
      of the Deltapmt4 mutant lysate. This caused decreased production of CTFalpha. We
      conclude that O-mannosylation is required for the solubilization of exogenously
      expressed human APP.

PMID- 19170768
TI  - Localization of gene products using a chromosomally tagged GFP-fusion library in
      the fission yeast Schizosaccharomyces pombe.
AB  - We constructed a library of chromosomally-tagged green fluorescent protein (GFP)
      fusions in the fission yeast Schizosaccharomyces pombe. This library contains
      1058 strains. In each strain, the coding sequence of GFP is integrated at the 3'
      end of a particular chromosomal ORF such that the full-length GFP fusion
      construct is expressed under the control of the original promoter. Integration of
      the GFP coding sequence at the authentic chromosomal location of each gene was
      confirmed by PCR. Microscopic screening of these strains detected sufficient
      levels of GFP signal in 710 strains and allowed assignment of these GFP-fusion
      gene products with their intracellular localization: 374 proteins were localized
      in the nucleus, 65 proteins in the nucleolus, 34 proteins at the nuclear
      periphery, 27 proteins at the plasma membrane and cytoplasmic membranous
      structures, 24 proteins at the spindle pole body and microtubules, 92 proteins at
      cytoplasmic structures, and 94 proteins were uniformly distributed throughout the
      cytoplasm.

PMID- 19170769
TI  - Focal adhesion-localization of START-GAP1/DLC1 is essential for cell motility and
      morphology.
AB  - There is a class of GTPase activating proteins for the Rho family GTPases
      (RhoGAPs) that contain the steroidogenic acute regulatory protein (STAR)-related
      lipid transfer (START) domain. In mammals three genes encode such proteins and
      they are designated START-GAP1-3 or deleted in liver cancer 1-3 (DLC1-3). In this
      study, we examined the intracellular localization and roles of START-GAP1/DLC1 in
      cell motility. Immunofluorescence microscopic analysis of NRK cells and HeLa
      cells revealed that START-GAP1 was localized in focal adhesions. Amino acid
      residues 265-459 of START-GAP1 were found to be necessary for focal adhesion
      targeting and we name the region "the focal adhesion-targeting (FAT) domain." It
      was previously known that ectopic expression of START-GAP1 induced cell rounding.
      We demonstrated that the FAT domain of START-GAP1 was partially required for this
      morphological change. Furthermore, expression of this domain in HeLa cells
      resulted in dissociation of endogenous START-GAP1 from focal adhesions as a
      dominant negative modulator, reducing cell migration and spreading. Taken
      together, START-GAP1 is targeted to focal adhesions via the FAT domain and
      regulates actin rearrangement through down-regulation of active RhoA and Cdc42.
      Its absence from focal adhesions could, therefore, cause abnormal cell motility
      and spreading.

PMID- 19170770
TI  - Transcriptional profiling of CD31(+) cells isolated from murine embryonic stem
      cells.
AB  - Identification of genes involved in endothelial differentiation is of great
      interest for the understanding of the cellular and molecular mechanisms involved
      in the development of new blood vessels. Mouse embryonic stem (mES) cells serve
      as a potential source of endothelial cells for transcriptomic analysis. We
      isolated endothelial cells from 8-days old embryoid bodies by immuno-magnetic
      separation using platelet endothelial cell adhesion molecule-1 (also known as
      CD31) expressed on both early and mature endothelial cells. CD31(+) cells exhibit
      endothelial-like behavior by being able to incorporate DiI-labeled acetylated low
      density lipoprotein as well as form tubular structures on matrigel. Quantitative
      and semi-quantitative PCR analysis further demonstrated the increased expression
      of endothelial transcripts. To ascertain the specific transcriptomic identity of
      the CD31(+) cells, large-scale microarray analysis was carried out. Comparative
      bioinformatic analysis reveals an enrichment of the gene ontology categories
      angiogenesis, blood vessel morphogenesis, vasculogenesis and blood coagulation in
      the CD31(+) cell population. Based on the transcriptomic signatures of the
      CD31(+) cells, we conclude that this ES cell-derived population contains
      endothelial-like cells expressing a mesodermal marker BMP2 and possess an
      angiogenic potential. The transcriptomic characterization of CD31(+) cells
      enables an in vitro functional genomic model to identify genes required for
      angiogenesis.

PMID- 19170772
TI  - Activities of Escherichia coli ribosomes in IF3 and RMF change to prepare 100S
      ribosome formation on entering the stationary growth phase.
AB  - The canonical ribosome cycle in bacteria consists of initiation, elongation,
      termination, and recycling stages. After the recycling stage, initiation factor 3
      (IF3) stabilizes ribosomal dissociation by binding to 30S subunits for the next
      round of translation. On the other hand, during the stationary growth phase, it
      has been elucidated that Escherichia coli ribosomes are dimerized (100S ribosome
      formation) by binding ribosome modulation factor (RMF) and hibernation promoting
      factor (HPF), leading to a hibernation stage. This indicates that 100S ribosomes
      are formed after these factors are scrambled for ribosomes concomitantly with
      transition from the log phase to the stationary phase. In this study, to
      elucidate the ribosomal events before 100S ribosome formation, the relationships
      between protein factors (RMF and HPF) involved in 100S ribosome formation and IF3
      involved in initiation complex formation were examined. As a result of in vitro
      assays, it was found that ribosomal dissociation activity by IF3 fell, and that
      ribosomal dimerization activity by RMF and HPF was elevated more when using
      stationary-phase ribosomes than when using log-phase ribosomes. This suggests
      that ribosomes change into forms which are hard to bind with IF3 and easy to form
      100S ribosomes by RMF and HPF concomitantly with transition from the log phase to
      the stationary phase.

PMID- 19170771
TI  - Human Nei-like protein NEIL3 has AP lyase activity specific for single-stranded
      DNA and confers oxidative stress resistance in Escherichia coli mutant.
AB  - Oxidative base damage leads to alteration of genomic information and is
      implicated as a cause of aging and carcinogenesis. To combat oxidative damage to
      DNA, cells contain several DNA glycosylases including OGG1, NTH1 and the Nei-like
      proteins, NEIL1 and NEIL2. A third Nei-like protein, NEIL3, is composed of an
      amino-terminal Nei-like domain and an unknown carboxy-terminal domain. In
      contrast to the other well-described DNA glycosylases, the DNA glycosylase
      activity and in vivo repair function of NEIL3 remains unclear. We show here that
      the structural modeling of the putative NEIL3 glycosylase domain (1-290) fits
      well to the known Escherichia coli Fpg crystal structure. In spite of the
      structural similarity, the recombinant NEIL3 and NEIL3(1-290) proteins do not
      cleave any of several test oligonucleotides containing a single modified base.
      Within the substrates, we detected AP lyase activity for single-stranded (ss) DNA
      but double-stranded (ds) DNA. The activity is abrogated completely in mutants
      with an amino-terminal deletion and at the zinc-finger motif. Surprisingly, NEIL3
      partially rescues an E. coli nth nei mutant from hydrogen peroxide sensitivity.
      Taken together, repair of certain base damage including base loss in ssDNA may be
      mediated by NEIL3.

PMID- 19170773
TI  - In vitro studies with 'acatalasemic-like' erythrocytes and hydrogen peroxide:
      attention to the formation of lysis resistant erythrocytes.
AB  - Hemolysis assays, using hydrogen peroxide as an oxidant injury agent and sodium
      azide as a catalase inhibitor, were performed to evaluate how assay conditions
      affect the development of lysis resistant erythrocytes. The concentration of
      hydrogen peroxide should be carefully selected for use in hemolysis assays, as it
      was found to affect the number of water resistant erythrocytes.

PMID- 19170774
TI  - The utility of immature reticulocyte fraction as an indicator of erythropoietic
      response to altitude training in elite cyclists.
AB  - Altitude training is sometimes employed by elite endurance athletes to improve
      their sea level performance. This improvement results from the increased red cell
      mass consequent upon the boost in erythropoietin (EPO) level that occurs as a
      response to the relatively hypoxic environment at high altitudes. We measured
      serum EPO levels together with various red cell and reticulocyte parameters
      including immature reticulocyte fraction (IRF) in eight national track-endurance
      cyclists, resident at sea-level, prior to and upon return from an altitude of
      approximately 1905 m. Reticulocytes and soluble transferrin receptor (sTfR) were
      significantly increased with reduction in ferritin levels immediately on return
      from high altitude indicating increased erythropoietic activity. IRF in
      particular showed a significant peak immediately on return but decline to sub
      baseline levels by day 9, and recovery to baseline by day 16. Our results
      indicate that IRF is a sensitive marker of erythropoietic status in athletes
      undergoing altitude training and subsequent loss of EPO stimuli on return to sea
      level.

PMID- 19170775
TI  - Role of RFLP using TspRI for carrier detection in Glanzmann's thrombasthenia: a
      report on two families.
AB  - Glanzmann's thrombasthenia (GT) was diagnosed in two patients who presented with
      bleeding manifestations accompanied by absent platelet aggregation, secondary to
      adenosine-5'-diphosphate, adrenaline, arachidonic acid and collagen. Flow
      cytometry analysis for GPIIb/IIIa expression was done using CD61 and CD41 markers
      in these patients and their family members including siblings. The patients were
      sub typed as Type I as he had absent glycoproteins (GP) IIb/IIIa. Family studies
      by flow cytometry showed reduced GPII/IIIa expression in both the parents and one
      sibling. However, western blot showed abnormal GPIIb protein in all the family
      members including siblings. It is possible that abnormal GPIIb protein by western
      blot in family members may reflect their carrier status. Patients' DNA was
      analyzed for mutation in both the GPIIb and GPIIIa genes by conformational
      sensitive gel electrophoresis (CSGE), followed by sequencing. CSGE showed defect
      in exon 12 and the promoter region of GPIIb. By sequence, it was confirmed that
      both the mutations were homozygous one was c.1028T>C and the other one was
      M33320.1:g.951G>A. For one of these mutations, restriction fragment length
      polymorphism (RFLP) was developed to look for the same mutation in all the family
      members. RFLP was developed using a restriction enzyme (TspRI) against the
      patient's mutation, c.1028T>C in exon 12 of GPIIb gene. RFLP followed by gel
      electrophoresis revealed that the mutation was heterozygous in all the family
      members. The findings by RFLP were double confirmed by direct DNA sequencing of
      the exon 12 in all the family members. Thus, TspRI marker may be used as a RFLP
      marker to predict the carriers in GT families, if the patients' mutation status
      is identified.

PMID- 19170776
TI  - Evaluation of Ves-Matic Cube 200--an automated system for the measurement of the
      erythrocyte sedimentation rate.
AB  - Ves-Matic Cube 200 is fully automated analyzer that performs erythrocyte
      sedimentation rate (ESR) measurement using the standard
      ethylenediaminetetraacetic acid blood sample tube, thus markedly reducing the
      analytical time and avoiding the need for an extra blood sample. The aim of this
      study was to assess the automatic Ves-Matic Cube 200 system for the measurement
      of ESR in comparison with the original International Council for Standardization
      in Hematology reference method (Westergren). The evaluation comprised accuracy
      which was established using a 95% confidence interval (CI) for the mean
      difference between Ves-Matic Cube 200 and Westergren method (mean of difference:
      0.47+/-6.84 mm/h; 95% CI: -0.376 to 1.325 mm/h), within-run imprecision for
      samples with ESR values of 9, 42 and 95 mm/h (coefficients of variation: 9.19%,
      13.88% and 5.66%, respectively) and method comparison (rho=0.95; Passing-Bablok
      regression equation: Y=-0.0435+1.0435 X; bias: -0.5; limits of agreement: -13.9
      to 12.9). Stability was estimated after 24 h storage either at 4 degrees C and
      room temperature (mean of differences: -1.91 mm/h; 95% CI: -4.852 to 1.037 mm/h
      and mean of differences: -12.48 mm/h; 95% CI: -16.580 to -8.390 mm/h,
      respectively). The obtained results suggest that the Ves-Matic Cube 200 automated
      analyzer is reliable system for the measurement of ESR in clinical laboratories.

PMID- 19170777
TI  - Emergency medical service attitudes toward geriatric prehospital care and
      continuing medical education in geriatrics.
AB  - OBJECTIVES: To understand the opinions of emergency medical service (EMS)
      providers regarding their ability to care for older adults, the domains of
      geriatric medicine in which they need more training, and the modality through
      which continuing education could be best delivered. DESIGN: Qualitative study
      using key informant interviews. SETTING: Prehospital EMS system in Rochester, New
      York. PARTICIPANTS: EMS providers, EMS instructors and administrators, emergency
      physicians, and geriatricians. MEASUREMENTS: Semistructured interviews were
      conducted using an interview guide that addressed knowledge and skill
      deficiencies, recommendations for improvement of geriatrics continuing education,
      and delivery methods of education. RESULTS: Participant responses were generally
      congruous despite the diverse backgrounds, and redundancy was achieved rapidly.
      All participants perceived a deficit in EMS education on the care of older
      adults, particularly related to communications with patients and skilled nursing
      facility staff. All desired more geriatric continuing education for EMS
      providers, especially in communications and psychosocial issues. Education was
      desired in various modalities. CONCLUSION: Further geriatric continuing education
      for EMS providers is needed. Some specific topics relate to medical issues, but a
      large proportion involve communications and psychosocial issues. Education should
      be delivered in a variety of modalities to meet the needs of the EMS community.
      Emerging on-line video technologies may bridge the gap between learners
      preferring classroom-based modailities and those preferring self-study modules.

PMID- 19170778
TI  - Functional trajectories in older persons admitted to a nursing home with
      disability after an acute hospitalization.
AB  - OBJECTIVES: To characterize the functional trajectories of older persons admitted
      to a nursing home with disability after an acute hospitalization. DESIGN:
      Prospective cohort study of 754 community-living persons aged 70 and older who
      were initially nondisabled in four essential activities of daily living (ADLs).
      SETTING: Greater New Haven, Connecticut. PARTICIPANTS: The analytical sample
      included 296 participants who were newly admitted to a nursing home with
      disability after an acute hospitalization. MEASUREMENTS: Information on nursing
      home admissions, hospitalizations, and disability in essential ADLs was
      ascertained during monthly telephone interviews for up to 9 years. Disability was
      defined as the need for personal assistance in bathing, dressing, walking inside
      one's home, or transferring from a chair. RESULTS: The median time to the first
      nursing home admission with disability after an acute hospitalization was 46
      months (interquartile range 27.5-75.5), and the mean number+/-standard deviation
      of ADLs that participants were disabled in upon admission was 3.0+/-1.2. In the
      month preceding hospitalization, 189 (63.9%) participants had no disability. The
      most common functional trajectory was discharged home with disability (46.3%),
      followed by continuous disability in the nursing home (27.4%), discharged home
      without disability (21.6%), and noncontinuous disability in the nursing home
      (4.4%). Only 96 (32.4%) participants returned home at (or above) their premorbid
      level of function. CONCLUSION: The functional trajectories of older persons
      admitted to a nursing home with disability after an acute hospitalization are
      generally poor. Additional research is needed to identify the factors responsible
      for these poor outcomes.

PMID- 19170779
TI  - The effect of age on functional and mortality outcomes after acute myocardial
      infarction.
AB  - OBJECTIVES: To determine the prevalence of post-myocardial infarction (MI)
      functional decline and to describe its association with chronological age in
      survivors of MI. DESIGN: Prospective observational registry. SETTING: Nineteen
      U.S. hospitals. PARTICIPANTS: Two thousand four hundred eighty-one patients with
      acute MI. MEASUREMENTS: Baseline and 1-year interviews identified subjects with
      functional decline, defined as a more than 5-point decline in Medical Outcomes
      Study 12-item Short Form Questionnaire (SF-12) Physical Component score or being
      "too ill" to provide a follow-up interview at 1 year. The relationship between
      age and functional decline was evaluated using logistic regression models
      adjusted for baseline SF-12 score, comorbidities, sociodemographics, and
      treatment characteristics. One-year mortality and a combined endpoint of death or
      decline were also compared across age. RESULTS: Of 2,009 patients who survived to
      1 year, 582 (29%) experienced a functional decline. In survivors, age was not
      associated with functional decline in unadjusted (odds ratio (OR)=0.95/decade,
      95% confidence interval (CI)=0.88-1.03) or multivariable (OR=0.94, 95% CI=0.85
      1.05) models. Although age was strongly associated with 1-year mortality
      (adjusted hazard ratio=1.42, 95% CI=1.21-1.66), there was no association between
      age and the combined endpoint of death or functional decline (adjusted OR=1.02,
      95% CI=0.92-1.12). CONCLUSION: More than one in four survivors of MI experiences
      a significant decline in physical function by 1 year. Although age is strongly
      associated with mortality, it had no association with functional decline. Because
      older patients have the same potential for favorable functional outcomes after an
      MI, age alone should not preclude aggressive treatment after an MI.

PMID- 19170780
TI  - Cost-effectiveness of increasing access to mammography through mobile mammography
      for older women.
AB  - OBJECTIVES: To compare the costs of mobile and stationary mammography and examine
      the incremental cost-effectiveness of using mobile mammography to increase
      screening rates. DESIGN: A cost-effectiveness analysis was performed using
      effectiveness data from a randomized clinical trial and modeling of costs
      associated with the mobile mammography intervention. SETTING: The trial involved
      60 community-based meal sites, senior centers, and clubs. PARTICIPANTS: Four
      hundred ninety-nine individuals were enrolled in the study, of whom 463 had
      outcome data available for analysis. MEASUREMENTS: Costs were calculated for
      stationary and mobile mammography, as well as costs due to differences in
      technology and film versus digital. Incremental cost-effectiveness (cost per
      additional screen) was modeled, and sensitivity analysis was performed by
      altering efficiency (throughput) and effectiveness based on subgroup data from
      the randomized trial. RESULTS: The estimated annual costs were $435,162 for a
      stationary unit, $539,052 for a mobile film unit, and $456, 392 for a mobile
      digital unit. Assuming mobile units are less efficient (50% annual volume), the
      cost per screen was $41 for a stationary unit, $86 for a mobile film unit, and
      $102 for a mobile digital unit. The incremental cost per additional screen were
      $207 for a mobile film unit and $264 for a mobile digital unit over a stationary
      unit. CONCLUSION: Although mobile mammography is a more effective way to screen
      older women, the absolute cost per screen of mobile units is higher, whereas the
      reimbursement is no different. Financial barriers may impede the widespread use
      of this approach.

PMID- 19170781
TI  - Comparison of functional outcomes associated with hospital at home care and
      traditional acute hospital care.
AB  - OBJECTIVES: To compare differences in the functional outcomes experienced by
      patients cared for in Hospital at Home (HaH) and traditional acute hospital care.
      DESIGN: Survey questionnaire of participants in a prospective nonrandomized
      clinical trial. SETTING: Three Medicare managed care health systems and a
      Veterans Affairs Medical Center. PARTICIPANTS: Two hundred fourteen community
      dwelling elderly patients who required acute hospital admission for community
      acquired pneumonia, exacerbations of chronic heart failure or chronic obstructive
      pulmonary disease, or cellulitis, 84 of whom were treated in HaH and 130 in an
      acute care hospital. INTERVENTION: Treatment in a HaH care model that substitutes
      for care provided in the traditional acute care hospital. MEASUREMENTS: Change in
      activity of daily living (ADL) and instrumental activity of daily living (IADL)
      scores from 1 month before admission to 2 weeks post admission to HaH or acute
      hospital and the proportion of groups that experienced improvement, no change, or
      decline in ADL and IADL scores. RESULTS: Patients treated in HaH experienced
      modest improvements in performance scores, whereas those treated in the acute
      care hospital declined (ADL, 0.39 vs -0.60, P=.10, range -12.0 to 7.0; IADL 0.74
      vs -0.70, P=.007, range -5.0 to 10.0); a greater proportion of HaH patients
      improved in function and smaller proportions declined or had no change in ADLs
      (44% vs 25%, P=.10) or IADLs (46% vs 17%, P=.04). CONCLUSION: HaH care is
      associated with modestly better improvements in IADL status and trends toward
      more improvement in ADL status than traditional acute hospital care.

PMID- 19170782
TI  - Nursing time devoted to medication administration in long-term care: clinical,
      safety, and resource implications.
AB  - OBJECTIVES: To quantify the time required for nurses to complete the medication
      administration process in long-term care (LTC). DESIGN: Time-motion methods were
      used to time all steps in the medication administration process. SETTING: LTC
      units that differed according to case mix (physical support, behavioral care,
      dementia care, and continuing care) in a single facility in Ontario, Canada.
      PARTICIPANTS: Regular and temporary nurses who agreed to be observed.
      MEASUREMENTS: Seven predefined steps, interruptions, and total time required for
      the medication administration process were timed using a personal digital
      assistant. RESULTS: One hundred forty-one medication rounds were observed. Total
      time estimates were standardized to 20 beds to facilitate comparisons. For a
      single medication administration process, the average total time was 62.0+/-4.9
      minutes per 20 residents on physical support units, 84.0+/-4.5 minutes per 20
      residents on behavioral care units, and 70.0+/-4.9 minutes per 20 residents on
      dementia care units. Regular nurses took an average of 68.0+/-4.9 minutes per 20
      residents to complete the medication administration process, and temporary nurses
      took an average of 90.0+/-5.4 minutes per 20 residents. On continuing care units,
      which are organized differently because of the greater severity of residents'
      needs, the medication administration process took 9.6+/-3.2 minutes per resident.
      Interruptions occurred in 79% of observations and accounted for 11.5% of the
      medication administration process. CONCLUSION: Time requirements for the
      medication administration process are substantial in LTC and are compounded when
      nurses are unfamiliar with residents. Interruptions are a major problem,
      potentially affecting the efficiency, quality, and safety of this process.

PMID- 19170783
TI  - Vision-enhancing interventions in nursing home residents and their short-term
      effect on physical and cognitive function.
AB  - OBJECTIVES: To evaluate the effect of vision-enhancing interventions (cataract
      surgery or refractive error correction) on physical function and cognitive status
      in nursing home residents. DESIGN: Longitudinal cohort study. SETTING: Seventeen
      nursing homes in Birmingham, Alabama. PARTICIPANTS: A total of 187 English
      speaking adults aged 55 and older. INTERVENTION: Participants took part in one of
      two vision-enhancing interventions: cataract surgery or refractive error
      correction. Each group was compared against a control group (persons eligible for
      but who declined cataract surgery or who received delayed correction of
      refractive error). MEASUREMENTS: Physical function (ability to perform activities
      of daily living and mobility) was assessed using a series of self-report and
      certified nursing assistant ratings at baseline and at 2 months for the
      refractive error correction group and at 4 months for the cataract surgery group.
      The Mini Mental State Examination was also administered. RESULTS: No significant
      differences existed within or between groups from baseline to follow-up on any of
      the measures of physical function. Mental status scores significantly declined
      from baseline to follow-up for the immediate (P=.05) and delayed (P<.02)
      refractive error correction groups and for the cataract surgery control group
      (P=.05). CONCLUSION: Vision-enhancing interventions did not lead to short-term
      improvements in physical functioning or cognitive status in this sample of
      elderly nursing home residents.

PMID- 19170784
TI  - Consensus guidelines for oral dosing of primarily renally cleared medications in
      older adults.
AB  - OBJECTIVES: To establish consensus oral dosing guidelines for primarily renally
      cleared medications prescribed for older adults. DESIGN: Literature search
      followed by a two-round modified Delphi survey. SETTING: A nationally
      representative survey of experts in geriatric clinical pharmacy. PARTICIPANTS:
      Eleven geriatric clinical pharmacists. MEASUREMENTS: After a comprehensive
      literature search and review by an investigative group of six physicians (2
      general internal medicine, 2 nephrology, 2 geriatrics), 43 dosing recommendations
      for 30 medications at various levels of renal function were created. The expert
      panel rated its agreement with each of these 43 dosing recommendations using a 5
      point Likert scale (1=strongly disagree to 5=strongly agree). Recommendation
      specific means and 95% confidence intervals were estimated. Consensus was defined
      as a lower 95% confidence limit of greater than 4.0 for the recommendation
      specific mean score. RESULTS: The response rate was 81.8% (9/11) for the first
      round. All respondents who completed the first round also completed the second
      round. The expert panel reached consensus on 26 recommendations involving 18
      (60%) medications. For 10 medications (chlorpropamide, colchicine, cotrimoxazole,
      glyburide, meperidine, nitrofurantoin, probenecid, propoxyphene, spironolactone,
      and triamterene), the consensus recommendation was not to use the medication in
      older adults below a specified level of renal function (e.g., creatinine
      clearance <30 mL/min). For the remaining eight medications (acyclovir,
      amantadine, ciprofloxacin, gabapentin, memantine, ranitidine, rimantadine, and
      valacyclovir), specific recommendations for dose reduction or interval extension
      were made. CONCLUSION: An expert panel of geriatric clinical pharmacists was able
      to reach consensus agreement on a number of oral medications that are primarily
      renally cleared.

PMID- 19170786
TI  - Montreal cognitive assessment performance in patients with Parkinson's disease
      with "normal" global cognition according to mini-mental state examination score.
AB  - OBJECTIVES: To examine Montreal Cognitive Assessment (MoCA) performance in
      patients with Parkinson's disease (PD) with "normal" global cognition according
      to Mini-Mental State Examination (MMSE) score. DESIGN: A cross-sectional
      comparison of the MoCA and the MMSE. SETTING: Two movement disorders centers at
      the University of Pennsylvania and the Philadelphia Veterans Affairs Medical
      Center. PARTICIPANTS: A convenience sample of 131 patients with idiopathic PD who
      were screened for cognitive and psychiatric complications. MEASUREMENTS: Subjects
      were administered the MoCA and MMSE, and only subjects defined as having a normal
      age- and education-adjusted MMSE score were included in the analyses (N=100). As
      previously recommended in patients without PD, a MoCA score less than 26 was used
      to indicate the presence of at least mild cognitive impairment (MCI). RESULTS:
      Mean MMSE and MoCA scores+/-standard deviation were 28.8+/-1.1 and 24.9+/-3.1,
      respectively. More than half (52.0%) of subjects with normal MMSE scores had
      cognitive impairment according to their MoCA score. Impairments were seen in
      numerous cognitive domains, including memory, visuospatial and executive
      abilities, attention, and language. Predictors of cognitive impairment on the
      MoCA using univariate analyses were male sex, older age, lower educational level,
      and greater disease severity; older age was the only predictor in a multivariate
      model. CONCLUSION: Approximately half of patients with PD with a normal MMSE
      score have cognitive impairment based on the recommended MoCA cutoff score. These
      results suggest that MCI is common in PD and that the MoCA is a more sensitive
      instrument than the MMSE for its detection.

PMID- 19170785
TI  - Stopping to rest during a 400-meter walk and incident mobility disability in
      older persons with functional limitations.
AB  - OBJECTIVES: To examine the association between stopping to rest during a 400-m
      usual-pace walk test (400-MWT) and incident mobility disability in older persons
      with functional limitations. DESIGN: Prospective cohort study. SETTING: Community
      based. PARTICIPANTS: Four hundred twenty-four participants in the Lifestyle
      Intervention and Independence for Elders Pilot (LIFE-P) Study aged 70 to 89 with
      functional limitations (summary score < or =9 on the Short Physical Performance
      Battery (SPPB)) but able to complete the 400-MWT within 15 minutes. MEASUREMENTS:
      Rest stops during the 400-MWT were recorded. The onset of mobility disability,
      defined as being unable to complete the 400-MWT or taking more than 15 minutes to
      do so, was recorded at Months 6 and 12. RESULTS: Fifty-four (12.7%) participants
      rested during the 400-MWT at baseline, of whom 37.7% experienced mobility
      disability during follow-up, versus 8.6% of those not stopping to rest.
      Performing any rest stop was strongly associated with incident mobility
      disability at follow-up (odds ratio (OR)=5.4, 95% confidence interval (CI)=2.7
      10.9) after adjustment for age, sex, and clinic site. This association was
      weaker, but remained statistically significant, after further adjusting for SPPB
      and time to complete the 400-MWT simultaneously (OR=2.6, 95% CI=1.2-5.9).
      CONCLUSION: Stopping to rest during the 400-MWT is strongly associated with
      incident mobility disability in nondisabled older persons with functional
      limitations. Given the prognostic value, rest stops should be recorded as part of
      the standard assessment protocol for the 400-MWT.

PMID- 19170787
TI  - Evaluation of the short form of the late-life function and disability instrument
      in geriatric inpatients-validity, responsiveness, and sensitivity to change.
AB  - OBJECTIVES: To evaluate the function component of the Short Form of the Late-Life
      Function and Disability Instrument (SF-LLFDI, German version) in geriatric
      inpatients and compare it with established performance-based and self-rated
      assessment tools. SETTING: Geriatric inpatient rehabilitation unit. PARTICIPANTS:
      One hundred fifty-six geriatric rehabilitation inpatients (44 men, 112 women)
      with a mean age of 81.7 who were capable of walking at baseline. MEASUREMENTS:
      Weekly assessments were performed from admission until discharge (3 weeks later)
      using the function component of the SF-LLFDI, the Barthel Index (BI), the Falls
      Efficacy Scale International (FES-I), gait characteristics, the Timed Up and Go
      Test, and the Short Physical Performance Battery. Baseline characteristics were
      measured at admission. Construct validity was evaluated using Spearman
      correlation coefficients, internal consistency was measured using Cronbach alpha,
      and sensitivity to change was estimated using standardized response means.
      RESULTS: The SF-LLFDI did not show significant floor or ceiling effects. Internal
      consistency was good, with alpha (function component sub-scores) equal to 0.80 to
      0.86. Convergent validity measures concerning performance-based scores were
      moderate to good, and correlations increased over time (correlation coefficient
      (r)=0.35-0.64). There was a high correlation with the FES-I (admission: r=0.61,
      discharge: r=0.76). Sensitivity to change was significant for all examined
      scores, with the BI outperforming all other instruments, although the SF-LLFDI
      showed better responsiveness than the BI regarding change characteristics over
      time. CONCLUSION: The SF-LLFDI is a reliable and valid self-report instrument to
      measure functional status in geriatric rehabilitation inpatients. It improves the
      assessment of clinically relevant responsiveness. Further research is warranted
      to improve its sensitivity to change.

PMID- 19170788
TI  - Real-time identification of serious infection in geriatric patients using
      clinical information system surveillance.
AB  - OBJECTIVES: To develop and characterize an automated syndromic surveillance
      mechanism for early identification of older emergency department (ED) patients
      with possible life-threatening infection. DESIGN: Prospective, consecutive
      enrollment, single-site observational study. SETTING: A large university medical
      center with an annual ED census of 75,273. PARTICIPANTS: Patients aged 70 and
      older admitted to the ED and having two or more systemic inflammatory response
      syndrome (SIRS) criteria during their ED stay. MEASUREMENTS: A search algorithm
      was developed to screen the census of the ED through its clinical information
      system. A study coordinator confirmed all patients electronically identified as
      having a probable infectious explanation for their visit. RESULTS: Infection
      accounted for 28% of ED and 34% of final hospital diagnoses. Identification using
      the software tool alone carried a 1.63 relative risk of infection (95% confidence
      interval CI51.09-2.44) compared with other ED patients sufficiently ill to
      require admission. Follow-up confirmation by a study coordinator increased the
      risk to 3.06 (95% CI52.11-4.44). The sensitivity of the strategy overall
      wasmodest (14%), but patients identified were likely to have an infectious
      diagnosis (specificity 598%). The most common SIRS criterion triggering the
      electronic notification was the combination of tachycardia and tachypnea.
      CONCLUSION: A simple clinical informatics algorithm can detect infection in
      elderly patients in real time with high specificity. The utility of this tool for
      research and clinical care may be substantial.

PMID- 19170789
TI  - A clinical framework for improving the advance care planning process: start with
      patients' self-identified barriers.
AB  - OBJECTIVES: To explore barriers to multiple advance care planning (ACP) steps and
      identify common barrier themes that impede older adults from engaging in the
      process as a whole. DESIGN: Descriptive study. SETTING: General medicine clinic.
      San Francisco County. PARTICIPANTS: One hundred forty-three English and Spanish
      speakers aged 50 and older (mean 61) enrolled in an advance directive preference
      study. MEASUREMENT: Six months after reviewing two advance directives, self
      reported ACP engagement and barriers to each ACP step were measured with open-
      and closedended questions using quantitative and qualitative (thematic content)
      analyses. RESULTS: Forty percent of participants did not contemplate ACP, 46% did
      not discuss with family or friends, 80% did not discuss with their doctor, and
      90% did not document ACP wishes. Six barrier themes emerged: perceiving ACP as
      irrelevant (84%), personal barriers (53%), relationship concerns (46%),
      information needs (36%), health encounter time constraints (29%), and problems
      with advance directives (29%). Some barriers were endorsed at all steps (e.g.,
      perceiving ACP as irrelevant). Others were endorsed at individual steps (e.g.,
      relationship concerns for family or friend discussions, time constraints for
      doctor discussion, and problems with advance directives for documentation).
      DISCUSSION: Perceiving ACP to be irrelevant was the barrier theme most often
      endorsed at every ACP step. Other barriers were endorsed at specific steps.
      Understanding ACP barriers may help clinicians prioritize and address them and
      may also provide a framework for tailoring interventions to improve ACP
      engagement.

PMID- 19170790
TI  - Persistent delirium predicts greater mortality.
AB  - OBJECTIVES: To examine the association between persistent delirium and 1-year
      mortality in newly admitted postacute care (PAC) facility patients with delirium
      who were followed regardless of residence. DESIGN: Observational cohort study.
      SETTING: Eight greater-Boston skilled nursing facilities specializing in PAC.
      PARTICIPANTS: Four hundred twelve PAC patients with delirium at admission after
      an acute hospitalization. MEASUREMENTS: Assessments were done at baseline and
      four follow-up times: 2, 4, 12, and 26 weeks. Delirium, defined using the
      Confusion Assessment Method, was assessed, as were factors used as covariates in
      analyses: age, sex, comorbidity, functional status, and dementia. The outcome was
      1-year mortality determined according to the National Death Index and
      corroborated using medical record and proxy telephone interview. RESULTS: Nearly
      one-third of subjects remained delirious at 6 months. Cumulative 1-year mortality
      was 39%. Independent of age, sex, comorbidity, functional status, and dementia,
      subjects with persistent delirium were 2.9 (95% confidence interval 51.9-4.4)
      times as likely to die during the 1-year follow-up as subjects whose delirium
      resolved. This association remained strong and significant in groups with and
      without dementia. Additionally, when delirium resolved, the risk of death
      diminished thereafter. CONCLUSION: In patients who were delirious at the time of
      PAC admission, persistent delirium was a significant independent predictor of 1
      year mortality.

PMID- 19170791
TI  - Discussion as a factor in racial disparity in advance directive completion at
      nursing home admission.
AB  - Studies have consistently shown racial disparities in advance directive
      completion for nursing home residents but have not examined whether this
      disparity is due to differences in interactions with healthcare providers. This
      study had two aims: to determine whether the racial disparity in advance
      directive completion by nursing home residents is related to differences in
      discussion of treatment restrictions with healthcare providers and to examine
      whether there is a racial disparity in perceptions of residents' significant
      others that additional discussions would be helpful. Participants were 2,171
      white or black (16% of sample) residents newly admitted to 59 nursing homes. Data
      were collected from structured interviews with residents' significant others and
      review of nursing home charts. Questions included whether advance directives were
      completed, whether treatment restrictions were discussed with the resident or
      family, and whether more discussion would have been helpful. Frequencies
      according to race were determined for each question; P-values and logistic
      regression models were obtained. Black residents were less likely to have
      completed any advance directives (P<.001), and they (P<.001) and their family
      members (P<.001) were less likely than whites to have discussed treatment
      restrictions with healthcare providers. Logistic regression models indicated that
      disparity in treatment restrictions narrowed when these discussions occurred.
      Significant others of black residents were more likely than those of white
      residents to consider further discussion helpful (P<.001), especially with
      physicians. Racial disparity in treatment restrictions may be due in part to a
      difference in discussion with healthcare providers; increasing discussion may
      narrow this disparity.

PMID- 19170792
TI  - May you live to be 120... Revised.

PMID- 19170793
TI  - Hochuekkito improves systemic inflammation and nutritional status in elderly
      patients with chronic obstructive pulmonary disease.

PMID- 19170794
TI  - Body mass index: pitfalls in elderly people.

PMID- 19170795
TI  - Handwashing and other environmental interventions needed to control viral
      infections in long-term care facilities.

PMID- 19170796
TI  - The choice of aspirin dose for primary prevention of embolic complications of
      nonvalvular atrial fibrillation in elderly people.

PMID- 19170797
TI  - Homicides of frail older persons by their caregivers in Japan.

PMID- 19170798
TI  - Successful maintenance hemodialysis in nonagenarians with end-stage renal disease
      and preexisting comorbidities.

PMID- 19170799
TI  - Vitamin D supplement intake in elderly fallers.

PMID- 19170800
TI  - Pioglitazone improved cognition in a pilot study on patients with Alzheimer's
      disease and mild cognitive impairment with diabetes mellitus.

PMID- 19170801
TI  - Dementia, delirium, and depression in patients with hip fracture: 1+1 doesn't
      always make 2.

PMID- 19170803
TI  - Botulinum toxin type A in the treatment of sialorrhea in Parkinson's disease.

PMID- 19170804
TI  - Antiepileptic drugs in the treatment of neuropathic pain: drug-to-drug
      interaction in elderly people.

PMID- 19170805
TI  - Utilization patterns of psychiatric emergency services by elderly patients.

PMID- 19170806
TI  - Is nursing home regulation a barrier to resident-centered care?

PMID- 19170808
TI  - Miller Fisher syndrome mistaken as stroke in an octogenarian.

PMID- 19170807
TI  - Emergency percutaneous aortic balloon valvuloplasty in a nonagenarian.

PMID- 19170809
TI  - Imitation can reduce malnutrition in residents in assisted living facilities.

PMID- 19170810
TI  - High prevalence and early complication of symptomatic vertebral fracture in
      elderly people treated with high-dose glucocorticoids.

PMID- 19170812
TI  - Skin diseases and sexually transmitted diseases in HIV-infected patients on HAART
      compared to a non-infected population - results of a retrospective study.
AB  - BACKGROUND: The prevalence of skin diseases and sexually transmitted diseases has
      always played a special role in studying HIV infections, both because of
      immunosuppression and simultaneous transmission. In the early years of the HIV
      epidemic, skin diseases were often a pathognomonic sign in heavily
      immunosuppressed patients. With highly active antiretroviral therapy (HAART), HIV
      infection has become a treatable chronic disease. For this reason the spectrum as
      well as the prevalence of skin diseases has changed. Pathognomonic skin diseases
      have become rare and the wide spectrum today ranges from infectious to iatrogenic
      skin diseases. PATIENTS AND METHODS: From April to October 2007 166 HIV-infected
      patients and 173 patients of a comparison group were surveyed in retrospect by
      means of a questionnaire about skin diseases and sexually transmitted diseases
      that appeared over the entire year 2006. RESULTS AND CONCLUSIONS: The study
      confirmed the shift to a wide variety of mostly trivial skin diseases and away
      from severe opportunistic skin diseases. HIV-infected patients today have more
      numerous skin problems than the non-infected population and thus need regular
      dermatologic control examinations.

PMID- 19170813
TI  - Prospective analysis of the incidence of autoimmune bullous disorders in Lower
      Franconia, Germany.
AB  - BACKGROUND: Only limited epidemiologic data are available on autoimmune bullous
      diseases. Improved diagnostic tools should have led to an increased incidence. To
      test this hypothesis, all patients with autoimmune bullous disorders who were
      treated in the Department of Dermatology at the University of Wurzburg, Germany,
      between January 2001 and June 2002 were analysed prospectively. PATIENTS AND
      METHODS: Epidemiologic data of patients diagnosed with an autoimmune bullous
      disease during this time period were registered and statistically evaluated.
      Diagnosis was based on the clinical picture and specific immunopathological
      findings. Only patients from Lower Franconia, a well-defined administrative
      region of Southern Germany, were included into this study. RESULTS: During the
      study period, 41 patients with an autoimmune bullous disease were diagnosed,
      including 27 with bullous pemphigoid, 4 with pemphigoid gestationis and mucous
      membrane pemphigoid, 2 with dermatitis herpetiformis and linear IgA disease, and
      1 with epidermolysis bullosa acquisita and pemphigus vulgaris, respectively. The
      highest incidence was calculated for bullous pemphigoid (13.4 per 1 million
      inhabitants per year) followed by pemphigoid gestationis (2.0) and mucous
      membrane pemphigoid (2.0). Patients with mucous membrane pemphigoid were found to
      have the highest mean age at disease onset (76 years) followed by patients with
      bullous pemphigoid (74 years). CONCLUSIONS: This is the first prospective study
      on the incidence of autoimmune bullous disorders. Subepidermal blistering
      autoimmune diseases were shown to be more frequent than previously reported for
      Central Europe. This is most likely due to improved diagnostic tools for and
      increased awareness of these diseases.

PMID- 19170814
TI  - Diet and social conditions during sexual maturation have unpredictable influences
      on female life history trade-offs.
AB  - The trade-off between gametes and soma is central to life history evolution.
      Oosorption has been proposed as a mechanism by which females can redirect
      nutrients invested in oocytes into survival when conditions for reproduction are
      poor. Although positive correlations between oocyte degradation and lifespan have
      been documented in oviparous insects, the adaptive significance of this process
      in species with more complex reproductive biology has not been explored. Further,
      environmental condition is a multivariate state, and combinations of
      environmental stresses may interact in unpredictable ways. Previous work on the
      ovoviviparous cockroach, Nauphoeta cinerea, revealed that females manipulated to
      mate late relative to sexual maturation experience age-related loss in fecundity
      because of loss of viable oocytes via apoptosis. This loss in fecundity is
      correlated with a reduction in female mate choice. Food deprivation while mating
      is delayed further increases levels of oocyte apoptosis, but the relationship
      between starvation-induced apoptosis and life history are unknown. To investigate
      this, virgin females were either fed or starved from eclosion until provided with
      a mate at a time known to be suboptimal for fertility. Following mating, females
      were fed for the duration of their lifespan. We measured lifetime reproductive
      performance. Contrary to predictions, under conditions of delayed mating
      opportunity, starved females had greater fecundity, gave birth to more high
      quality offspring and had increased longevity compared with that of fed females.
      We suggest that understanding proximal mechanisms underlying life history trade
      offs, including the function of oocyte apoptosis, and how these mechanisms
      respond to varied environmental conditions is critical.

PMID- 19170815
TI  - Mating triggers dynamic immune regulations in wood ant queens.
AB  - Mating can affect female immunity in multiple ways. On the one hand, the immune
      system may be activated by pathogens transmitted during mating, sperm and seminal
      proteins, or wounds inflicted by males. On the other hand, immune defences may
      also be down-regulated to reallocate resources to reproduction. Ants are
      interesting models to study post-mating immune regulation because queens mate
      early in life, store sperm for many years, and use it until their death many
      years later, while males typically die after mating. This long-term commitment
      between queens and their mates limits the opportunity for sexual conflict but
      raises the new constraint of long-term sperm survival. In this study, we examine
      experimentally the effect of mating on immunity in wood ant queens. Specifically,
      we compared the phenoloxidase and antibacterial activities of mated and virgin
      Formica paralugubris queens. Queens had reduced levels of active phenoloxidase
      after mating, but elevated antibacterial activity 7 days after mating. These
      results indicate that the process of mating, dealation and ovary activation
      triggers dynamic patterns of immune regulation in ant queens that probably
      reflect functional responses to mating and pathogen exposure that are independent
      of sexual conflict.

PMID- 19170816
TI  - The evolutionary dynamics of evolvability in a gene network model.
AB  - Evolvability, the ability of populations to adapt, has recently emerged as a
      major unifying concept in biology. Although the study of evolvability offers new
      insights into many important biological questions, the conceptual bases of
      evolvability, and the mechanisms of its evolution, remain controversial. We used
      simulated evolution of a model of gene network dynamics to test the contentious
      hypothesis that natural selection can favour high evolvability, in particular in
      sexual populations. Our results conclusively demonstrate that fluctuating natural
      selection can increase the capacity of model gene networks to adapt to new
      environments. Detailed studies of the evolutionary dynamics of these networks
      establish a broad range of validity for this result and quantify the evolutionary
      forces responsible for changes in evolvability. Analysis of the genotype
      phenotype map of these networks also reveals mechanisms connecting evolvability,
      genetic architecture and robustness. Our results suggest that the evolution of
      evolvability can have a pervasive influence on many aspects of organisms.

PMID- 19170817
TI  - Rapid changes in plasticity across generations within an expanding cedar forest.
AB  - We investigated the inter-individual variation of phenotypic plasticity and its
      evolution across three generations within an expanding forest. Plasticity was
      assessed in situ from dendrochronological data as the response of radial growth
      to summer rainfall. A linear mixed model was used to account for spatial effects
      (environment and stand structure), temporal factors (stand dynamics) and the
      variation with age. Beyond these effects, our results reveal a significant inter
      individual variance of growth and plasticity within each generation. We also show
      that the mean values and variances of growth and plasticity changed significantly
      across generations, with different patterns for both traits. The possible
      environmental and genetic drivers of these changes are discussed. Contrasting
      with the trade-off between stress tolerance and plasticity generally observed
      among populations, we detected a positive covariance at the individual level,
      which does not support the cost of plasticity hypothesis in this case.

PMID- 19170818
TI  - Persistence of costly novel genes in the absence of positive selection.
AB  - Many genetic changes that ultimately lead to adaptive evolution come with a short
      term cost expressed in terms of reduced survival and reproduction. In the absence
      of genetic drift, it is unclear how such costly mutations may persist. Here we
      experimentally demonstrate that parasites can promote the persistence of costly
      genetic variants. We employed a genetically engineered strain (GMMO) of the
      bacterium Pseudomonas fluorescens as a model of the acquisition of a new gene
      either through a major mutation or through horizontal transfer, and examined its
      persistence in different evolving communities comprising an ancestral strain and
      a lytic bacteriophage. Whereas competition resulted in the elimination of the
      GMMO, inclusion of the phage promoted GMMO persistence. We provide evidence for
      why this effect is due to the differential susceptibility of GMMO and ancestral
      bacteria to phage.

PMID- 19170819
TI  - Divergence along a steep ecological gradient in lake whitefish (Coregonus sp.).
AB  - To understand mechanisms structuring diversity in young adaptive radiations,
      quantitative and unbiased information about genetic and phenotypic diversity is
      much needed. Here, we present the first in-depth investigation of whitefish
      diversity in a Swiss lake, with continuous spawning habitat sampling in both time
      and space. Our results show a clear cline like pattern in genetics and morphology
      of populations sampled along an ecological depth gradient in Lake Neuchatel.
      Divergent natural selection appears to be involved in shaping this cline given
      that trait specific P(ST)-values are significantly higher than F(ST)-values when
      comparing populations caught at different depths. These differences also tend to
      increase with increasing differences in depth, indicating adaptive divergence
      along a depth gradient, which persists despite considerable gene flow between
      adjacent demes. It however remains unclear, whether the observed pattern is a
      result of currently stable selection-gene flow balance, incipient speciation, or
      reverse speciation due to anthropogenic habitat alteration causing two formerly
      divergent species to collapse into a single gene pool.

PMID- 19170820
TI  - Selective nectar robbing in a gynodioecious plant (Glechoma longituba) enhances
      female advantage.
AB  - Nectar robbing not only affects the reproductive fitness of the plant but it may
      also potentially affect the pollination dynamics of the associated coflowering
      individuals. In this study, we established that the nectar robber Xylocopa
      sinensis robs nectar only from the hermaphrodite ramets of the gynodioecious
      plant Glechoma longituba but not from the female ramets. In populations with high
      rates of nectar robbing, this results in hermaphrodite ramets having reduced seed
      set whereas the female ramets have a slightly increased seed set. We hypothesize
      that selective nectar robbing confers an advantage to female individuals and thus
      ensures their maintenance in gynodioecious populations. Results of controlled
      experiments indicated that the reduction in the amounts of nectar available
      occasioned by nectar robbing resulted in some legitimate pollinators switching to
      visiting flowers on female rather than hermaphrodite ramets. This resulted in
      lower pollination rates and seed set for hermaphrodites and higher pollination
      rates and seed set for females. This study presents a previously unreported
      mechanism causing female advantage in gynodioecious plants.

PMID- 19170821
TI  - Tracking the origin of an invasive species: Drosophila subobscura in Argentina.
AB  - Biological invasions are excellent opportunities to study the evolutionary forces
      leading to the adaptation of a species to a new habitat. Knowledge of the
      introduction history of colonizing species helps tracking colonizing routes and
      assists in defining management strategies for invasive species. The Palearctic
      species Drosophila subobscura is a good model organism for tracking colonizations
      since it was detected in Chile and western North America three decades ago and
      later on in the Atlantic coast of Argentina. To unravel the origin of the
      Argentinean colonizers two populations have been analysed with several genetic
      markers. Chromosomal arrangements and microsatellite alleles found in Argentina
      are almost similar to those observed in Chile and USA. The lethal allelism test
      demonstrates that the lethal gene associated with the O(5) inversions in
      Argentina is identical to that found in Chile and USA, strongly supporting the
      hypothesis that all the American colonizing populations originated from the same
      colonization event. A secondary bottleneck is detected in the Argentinean
      populations and the genetic markers suggest that these populations originated
      from the invasion of 80-150 founding individuals from Chile.

PMID- 19170822
TI  - Selection efficiency and effective population size in Drosophila species.
AB  - A corollary of the nearly neutral theory of molecular evolution is that the
      efficiency of natural selection depends on effective population size. In this
      study, we evaluated the differences in levels of synonymous polymorphism among
      Drosophila species and showed that these differences can be explained by
      differences in effective population size. The differences can have implications
      for the molecular evolution of the Drosophila species, as is suggested by our
      results showing that the levels of codon bias and the proportion of adaptive
      substitutions are both higher in species with higher levels of synonymous
      polymorphism. Moreover, species with lower synonymous polymorphism have higher
      levels of nonsynonymous polymorphism and larger content of repetitive sequences
      in their genomes, suggesting a diminished efficiency of selection in species with
      smaller effective population size.

PMID- 19170823
TI  - Social context predicts recognition systems in ant queens.
AB  - Recognition of group-members is a key feature of sociality. Ants use chemical
      communication to discriminate nestmates from intruders, enhancing kin cooperation
      and preventing parasitism. The recognition code is embedded in their cuticular
      chemical profile, which typically varies between colonies. We predicted that ants
      might be capable of accurate recognition in unusual situations when few
      individuals interact repeatedly, as new colonies started by two to three queens.
      Individual recognition would be favoured by selection when queens establish
      dominance hierarchies, because repeated fights for dominance are costly; but it
      would not evolve in absence of hierarchies. We previously showed that
      Pachycondyla co-founding queens, which form dominance hierarchies, have accurate
      individual recognition based on chemical cues. Here, we used the ant Lasius niger
      to test the null hypothesis that individual recognition does not occur when co
      founding queens do not establish dominance hierarchies. Indeed, L. niger queens
      show a similar level of aggression towards both co-foundresses and intruders,
      indicating that they are unable of individual recognition, contrary to
      Pachycondyla. Additionally, the variation in chemical profiles of Lasius and
      Pachycondyla queens is comparable, thus informational constraints are unlikely to
      apply. We conclude that selection pressure from the social context is of crucial
      significance for the sophistication of recognition systems.

PMID- 19170824
TI  - Sex and asymmetry in humans: what is the role of developmental instability?
AB  - Because asymmetric individuals are less attractive and may suffer from reduced
      fitness, bilateral asymmetry is widely believed to affect human sexual selection.
      Its evolutionary significance is based on the presumed relationship with
      developmental instability (DI). Yet, relationships between DI and bilateral
      asymmetry are often weak and possibly confounded by asymmetric mechanical
      loadings because of handedness. We related asymmetry in hands and faces to
      degrees of handedness and sexual behaviour in 100 humans. Handedness correlated
      to levels of asymmetry, thereby likely invalidating the use of asymmetry to
      estimate DI. For facial asymmetry, applying existing theoretical models refuted a
      link between asymmetry and DI. Explicit statistical modelling at the level of DI
      confirmed the absence of a link between DI and aspects of sexual behaviour.
      Nevertheless, asymmetries in both hands and face correlated significantly with
      sexual behaviour. We conclude that bilateral asymmetry per se, rather than its
      presumed link with DI, more likely relates to measures of human sexual behaviour.
      Because lateralization of behaviour appears widespread, evaluating the role of DI
      in evolution and ecology relies on a very critical selection of traits whose
      asymmetry can reliably reflect DI.

PMID- 19170825
TI  - Phenotypic plasticity of a cooperative behaviour in bacteria.
AB  - There is strong evidence that natural selection can favour phenotypic plasticity
      as a mechanism to maximize fitness in animals. Here, we aim to investigate
      phenotypic plasticity of a cooperative trait in bacteria--the production of an
      iron-scavenging molecule (pyoverdin) by Pseudomonas aeruginosa. Pyoverdin
      production is metabolically costly to the individual cell, but provides a benefit
      to the local group and can potentially be exploited by nonpyoverdin-producing
      cheats. Here, we subject bacteria to changes in the social environment in media
      with different iron availabilities and test whether cells can adjust pyoverdin
      production in response to these changes. We found that pyoverdin production per
      cell significantly decreased at higher cell densities and increased in the
      presence of cheats. This phenotypic plasticity significantly influenced the costs
      and benefits of cooperation. Specifically, the investment of resources into
      pyoverdin production was reduced in iron-rich environments and at high cell
      densities, but increased under iron limitation, and when pyoverdin was exploited
      by cheats. Our study demonstrates that phenotypic plasticity in a cooperative
      trait as a response to changes in the environment occurs in even the simplest of
      organisms, a bacterium.

PMID- 19170826
TI  - Pitfalls in understanding the functional significance of genital allometry.
AB  - The male genitalia of arthropods consistently show negative static allometry (the
      genitalia of small males of a species are disproportionally large, and those of
      large males are disproportionally small). We discuss relations between the 'one
      size-fits-all' hypothesis to explain this allometry and the regimes of selection
      that may be acting on genitalia. We focus on the contrasts between directional
      vs. stabilizing selection, and natural vs. sexual selection. In addition, we
      point out some common methodological problems in studies of genital allometry.
      One-size-fits-all types of arguments for negative allometry imply net stabilizing
      selection, but the effects of stabilizing selection on allometry will be weaker
      when the correlation between body size and the trait size is weaker. One-size
      fits-all arguments can involve natural as well as sexual selection, and negative
      allometry can also result from directional selection. Several practical problems
      make direct tests of whether directional or stabilizing selection is acting
      difficult. One common methodological problem in previous studies has been
      concentration on absolute rather than relative values of the allometric slopes of
      genitalia; there are many reasons to doubt the usefulness of comparing absolute
      slopes with the usual reference value of 1.00. Another problem has been the
      failure to recognize that size and shape are independent traits of genitalia;
      rapid divergence in the shape of genitalia is thus not paradoxical with respect
      to the reduced variation in their sizes that is commonly associated with negative
      allometric scaling.

PMID- 19170830
TI  - Testosterone replacement therapy in naturally and surgically menopausal women.
AB  - INTRODUCTION: Testosterone replacement therapy in naturally and surgically
      menopausal women is a complex and currently highly debated topic. Opposing
      guidelines for the use of testosterone exist, which create a therapeutic dilemma
      for clinicians confronted by severely distressed women who experience a decrease
      in sexual desire after surgical or natural menopause. AIM: In this review, we
      will address the current knowledge on androgen physiology, conditions associated
      with a low androgen state, and risks and benefits of androgen therapy. METHODS:
      An English-language Medline review was performed. MAIN OUTCOME MEASURE: Review of
      available literature. RESULTS: A review of normal androgen physiology in women is
      summarized and a brief review of prior use of androgens over the last six decades
      is included. The data on the use of androgen replacement in pre- and
      postmenopausal women is evaluated, especially its relationship to sexual
      functioning. Special concerns about the effect of androgens on cardiovascular
      disease, breast, and endometrial tissue are discussed. The balance of evidence
      seems to show that androgens have more of a positive effect than a negative
      effect in women if used properly. CONCLUSIONS: Testosterone replacement therapy
      for surgically and naturally menopausal women with low sexual desire can be
      accomplished physiologically and effectively after ruling out other medical
      conditions leading to low sexual desire and after proper information of the
      patient that testosterone therapy is not an FDA-approved medication in the United
      States. The majority of available data suggests that testosterone replacement in
      women can be used safely without increased risk of endometrial or breast cancer.

PMID- 19170832
TI  - Subcutaneous testosterone pellet implantation procedure for treatment of
      testosterone deficiency syndrome.

PMID- 19170835
TI  - Female urinary incontinence during intercourse: a review on an understudied
      problem for women's sexuality.
AB  - INTRODUCTION: Coital urinary incontinence is a frequently underreported symptom,
      with a relevant impact on women's sexuality and quality of life. AIM: This
      article will review the available evidence on incidence, pathophysiology, and
      treatment of coital urinary incontinence with the attempt to present the current
      state of the art. METHODS: PubMed was searched for reports about coital urinary
      incontinence that were published from 1970 to 2008, and the most relevant
      articles were reviewed. MAIN OUTCOME MEASURES: Review on epidemiology,
      pathophysiology, diagnosis, and treatment of coital incontinence. RESULTS: The
      incidence of coital incontinence in incontinent women has been reported to range
      between 10% and 27%. At present, some evidence suggests an association between
      urinary leakage at penetration and urodynamic stress (USI) incontinence as well
      as urinary leakage during orgasm and detrusor overactivity (DO). When treatment
      for these conditions are based upon urodynamic findings, pelvic floor muscle
      training, surgery, and pharmacotherapy show satisfactory cure rates. CONCLUSIONS:
      Coital urinary incontinence deserves much more attention in clinical practice:
      women should be specifically interviewed for this disturbance because it has a
      very negative impact on their sexuality. If a reliable urodynamic diagnosis is
      made, coital urinary incontinence at penetration can be cured in more than 80% of
      cases by surgery in the presence of USI. The form of coital incontinence during
      orgasm is curable by antimuscarinic treatment in about 60% of cases when
      associated with DO.

PMID- 19170834
TI  - The effects of hypoestrogenism on the vaginal wall: interference with the normal
      sexual response.
AB  - INTRODUCTION: The sexual response depends on the adequate function of all systems
      related to the genital and extra-genital organs. Physiological conditions such as
      menopause can interfere with sexual expression because of central and peripheral
      changes. Genital effects of estrogen include vaginal trophism, lubrication, and
      local pleasure sensation in the sexual arousal phase. Hypoestrogenism causes
      changes in the four layers of the vaginal wall that may result in dyspareunia and
      a loss in the quality of the genital arousal response. AIM: The purpose of this
      review is to highlight the changes in the vaginal wall caused by hypoestrogenism,
      its possible relationship with dyspareunia, and its repercussions for genital
      arousal. Treatments for hypoestrogenism are also discussed. METHODS: We evaluated
      the data available in PubMed (1982-2008) and surveyed the reference list for
      relevant studies. Two reviewers analyzed the data independently. A study was
      considered to be of high quality if it had all three of the following
      characteristics: (i) prospective design; (ii) valid data; and (iii) adequate
      sample size. Reviews and experimental animal studies were also considered. MAIN
      OUTCOME MEASURES: Normal genital morphology, hypoestrogenism and hormone
      replacement therapy were the focus of the studies reviewed in this paper.
      RESULTS: Atrophy of the vaginal wall may be associated with dyspareunia and
      genital sexual arousal disorder, but psychological and sociocultural aspects must
      also be considered. Regardless, however, local estrogen therapy is useful in
      improving vaginal wall trophism and, thus, in improving the sexual response.
      CONCLUSIONS: There are many possible alterations in the structure of the vaginal
      wall that are related to estrogen deficiency that may require medical
      intervention beyond the usual strategies used to attain adequate sexual function.
      Physicians should attempt to treat these alterations, and more research is needed
      to elucidate the physiopathology of dyspareunia and genital sexual arousal
      physiology.

PMID- 19170836
TI  - Putative role of carbon monoxide signaling pathway in penile erectile function.
AB  - INTRODUCTION: Erectile response depends on nitric oxide (NO) generated by NO
      synthase (NOS) enzyme of the nerves and vascular endothelium in the cavernous
      tissue. NO activates soluble guanylate cyclase (sGC), leading to the production
      of cyclic guanosine monophosphate (cGMP). cGMP activates cGMP-dependent protein
      kinase that activates Ca(2+)/ATPase pump that activates Ca(2+)/K efflux pump
      extruding Ca(2+) across the plasma membrane with consequent smooth muscle cell
      relaxation. A role similar to that of NOS/NO signaling has been postulated for
      carbon monoxide (CO) produced in mammals from heme catabolism by heme oxygenase
      (HO) enzyme. AIM: To assess CO signaling pathway for erectile function by
      reviewing published studies. METHODS: A systematic review of published studies on
      this affair based on Pubmed and Medical Subject Heading databases, with search
      for all concerned articles. MAIN OUTCOME MEASURES: Documentation of positive as
      well as negative criteria of CO/HO signaling focused on penile tissue. RESULTS:
      The concept that HO-derived CO could play a role in mediating erectile function
      acting in synergism with, or as a potentiator for, NOS/NO signaling pathway is
      gaining momentum. CO/HO signaling pathway has been shown to partially mediate the
      actions of oral phosphodiesterase type 5 inhibitors. In addition, it was shown
      that the use of CO releasing molecules potentiated cavernous cGMP levels.
      However, increased CO production or release was reported to be associated, in
      some studies, with vasoconstriction. CONCLUSION: This review sheds a light on the
      significance of cavernous tissue CO signaling pathway that may pave the way for
      creation of therapeutic modalities based on this pathway.

PMID- 19170837
TI  - Sexual functioning of Latino women seeking outpatient gynecologic care.
AB  - INTRODUCTION: A sample of Latino women from an ambulatory obstetrics and
      gynecology (Ob/Gyn) clinic were queried about their sexual functioning using the
      Changes in Sexual Functioning Questionnaire (CSFQ-14). AIM: To assess the degree
      of self-reported sexual complaints in a sample of Latino women living in the
      United States; to assess if the prevalence of symptoms differs from one study of
      women living in Spain; and to determine if sexual complaints were associated with
      demographics, sexual/reproductive history, selected medications, or religious
      practices. MAIN OUTCOME MEASURES: CSFQ-14 scores and demographic variables.
      METHODS: CSFQ-14 questionnaire in an out-patient, bilingual Ob/Gyn clinic in
      Central Virginia. RESULTS: Seventy-one native Spanish-speaking patients (59% born
      in Mexico) completed the U.S. Spanish version of the CSFQ-14 and a short
      questionnaire for potential covariates. The mean age was 28.7 years (range 17
      60). Birth place was outside of the United States for 95.8% (N = 67). Eighty
      percent of participants had children and 96% reported being currently sexually
      active. Low sexual functioning, as defined by a total CSFQ score of < or = 41,
      was found in 26 (41.3%) participants. Taking medication for depression and/or
      anxiety was associated with lower sexual functioning (P = 0.03). Women who had
      children of any age living in the household were less likely to report low sexual
      functioning (P = 0.05; P = 0.01 when restricted to infants) than women without
      children living in the household. Thirteen of 68 women (19.1%) reported a history
      of physical and/or sexual abuse, but this was not associated with low sexual
      functioning. There was no association between self-reported religious affiliation
      or church attendance frequency and sexual complaints. Respondents in our sample
      had lower (i.e., worse sexual function) overall CSFQ scores compared with a
      sample of college students in Spain (P < 0.01), but higher (i.e., better sexual
      function) overall scores than workers in Spain (P < 0.04). On the subscales, our
      Latino population reported greater pleasure and less desire/interest than women
      who live in Spain. CONCLUSIONS: Self-reported rates of low sexual functioning
      were common in this cross section of Latino women. Medical treatment of
      depression and/or anxiety was associated with lower functioning. Direct inquiry
      about the sexual health of U.S. Latino women presenting for routine health care
      may assist in the identification of sexual difficulties in this population.

PMID- 19170838
TI  - Disappearance of female genital mutilation from the Bedouin population of
      Southern Israel.
AB  - INTRODUCTION: Recently, clinicians in Southern Israel perceived that the practice
      of female genital mutilation had disappeared entirely in the Bedouin population.
      We previously studied the prevalence of this practice in 1995. AIM: We decided to
      survey again the Bedouin population focusing on those tribes previously reported
      to perform this practice. METHODS: Eighty percent of the interviews were done by
      an Arabic-speaking psychiatrist and 20% were done by an Arabic speaking nurse in
      the gynecologic clinic of a large Bedouin township or the gynecologic clinic of a
      smaller Bedouin township. Women were asked if they would be willing to answer a
      few questions about their past and if they were willing to have the gynecologist,
      with no additional procedure, note whether any operation had been performed on
      their genitalia. MAIN OUTCOME MEASURES: Physical examination by gynecologist and
      an oral questionnaire. RESULTS: One hundred and thirty two women were examined.
      No cases of any scarring of the kind reported in the previous study were found on
      physical examination. CONCLUSIONS: FGM has apparently disappeared over 15 years
      in a population in which it was once prevalent.

PMID- 19170839
TI  - Sexual activity, erectile dysfunction and their correlates among 1,566 older
      Chinese men in Southern China.
AB  - INTRODUCTION: Few studies on sexuality and its correlates in adults have been
      conducted in Asia; most studies in Asia have focused instead on erectile
      dysfunction in men rather than sexuality or sexual activities. AIM: This study
      was conducted to evaluate the prevalence and factors associated with sexual
      activity and erectile dysfunction in elderly Chinese men aged 65 years and above.
      MAIN OUTCOME MEASURES: Sexual activity and sexual functions were assessed using
      the International Index of Erectile Function-5. Depressive symptoms were measured
      by the Chinese version of the Geriatric Depression Scale. Lower urinary tract
      symptoms (LUTS) were measured by the International Prostatic Symptom Score.
      METHODS: Cross-sectional data from a large prospective cohort study of Chinese
      elderly men were used in this study. A questionnaire that included demographic,
      lifestyle, and medical risk factors and physical examination were administered to
      1566 Chinese men aged between 65 to 92 years in Hong Kong. RESULTS: Only 30.7% of
      men were sexually active in the previous 6 months in this sample and among those
      who were sexually active, 88% had some form of erectile dysfunction. Being
      sexually inactive in the previous 6 months was associated with being older (odds
      ratio [OR] = 1.80; confidence interval [CI]: 1.56-2.09), single (OR = 1.87; CI =
      1.19-2.94) and the presence of peripheral arterial disease (OR = 2.43; CI: 1.25
      4.71). In multiple multinomial logistic regression, having clinically relevant
      depressive symptoms (OR = 3.37; CI: 1.31-8.70) and having moderate to severe LUTS
      (OR = 1.63; CI: 1.01-2.64) were independently associated with increased risk of
      having erectile dysfunction. CONCLUSION: We showed that a large proportion of
      elderly men were not sexually active in Hong Kong. For those who were sexually
      active, most suffered from some degree of erectile dysfunction. Having clinically
      relevant depressive symptoms and LUTS were independently associated with
      increased risk of erectile dysfunction.

PMID- 19170840
TI  - Atorvastatin ameliorates sildenafil-induced penile erections in experimental
      diabetes by inhibiting diabetes-induced RhoA/Rho-kinase signaling
      hyperactivation.
AB  - INTRODUCTION: One of the proposed mechanisms responsible for diabetes-related
      erectile dysfunction (ED) is overactivity of RhoA/ROCK signaling, as seen in
      experimental models of chemical diabetes. AIM: Because statins may interfere with
      RhoA/Rho-kinase (ROCK) signaling through the reduction of geranyl-geranyl
      pyrophosphate (GGPP), required for RhoA activation, we investigated whether
      atorvastatin ameliorated diabetes-related ED. METHODS: Streptozotocin-induced (8
      weeks) diabetic rats and alloxan-induced (8 weeks) diabetic rabbits received
      atorvastatin (5 mg/kg daily) for the last 2 weeks. In vitro contractility studies
      were conducted in the rabbit model. In the rat model, sildenafil effect on
      electrical stimulation (ES)-induced erection was investigated. Atorvastatin
      action was also analyzed using human fetal penile smooth muscle cells (hfPSMCs)
      exposed to low (5 mM), high (22 mM), and very high (40 mM) glucose. MAIN OUTCOME
      MEASURES: Atorvastatin effect on hyperglycemia-induced RhoA/ROCK signaling was
      evaluated using the ROCK inhibitor Y-27632 in both animal models and by analyzing
      functional effects downstream to RhoA activation in hfPSMCs. RESULTS: In both
      diabetic models, atorvastatin did not affect glycemia, lipid plasma levels, and
      the hypogonadal state. In diabetic rats, atorvastatin ameliorated the erectile
      response to the ES of the cavernous nerve and normalized sildenafil effect on
      erectile function, strongly decreased by diabetes. In penile tissue from diabetic
      animals, atorvastatin completely restored the diabetes-induced hypersensitivity
      to Y-27632 and prevented RhoA membrane translocation/activation. In hfPSMCs, high
      glucose significantly increased not only membrane RhoA expression, but also ROCK
      activity (increased phosphorylation of the ROCK substrate myosin phosphatase
      target subunit 1) and several RhoA-dependent functions such as proliferation,
      migration, and smooth muscle-related gene expression. Atorvastatin restored all
      the high-glucose-induced effects, an action specifically reverted by GGPP.
      CONCLUSION: Atorvastatin improves diabetes-related ED and restores sildenafil
      responsiveness, most probably by inhibiting RhoA/ROCK signaling, which underlies
      several high-glucose-induced derangements in penile smooth muscle cell
      commitment.

PMID- 19170841
TI  - Circulating CD34+ KDR+ endothelial progenitor cells correlate with erectile
      function and endothelial function in overweight men.
AB  - INTRODUCTION: Bone marrow-derived endothelial progenitor cells (EPCs) circulate
      in the peripheral blood and are involved in endothelial homeostasis and repair.
      AIM: The aim of this study was to assess the circulating levels of different EPC
      phenotypes in overweight men with or without erectile dysfunction (ED). As
      endothelial dysfunction is considered a necessary link with ED, endothelium
      dependent vasodilation and its relation with EPCs were also investigated.
      METHODS: We studied 30, otherwise healthy, overweight subjects with symptomatic
      ED for at least 6 months, and 30 age- and weight-matched subjects without ED.
      Erectile function was assessed by completing the International Index of Erectile
      Function (IIEF-5), which consists of items 5, 15, 4, 2, and 7 from the full-scale
      IIEF-15. MAIN OUTCOME MEASURES: Seven subpopulations of EPCs were determined by
      flow cytometry on the basis of the surface expression of CD34, CD133, and KDR
      antigens: CD34(+), CD133(+), KDR(+), CD34(+)CD133(+), CD34(+)KDR(+),
      CD133(+)KDR(+), and CD34(+)CD133(+)KDR(+). Endothelium-dependent flow-mediated
      dilation (FMD) was evaluated in the right brachial artery with a high-resolution
      ultrasound machine following reactive hyperemia. RESULTS: CD34(+)KDR(+) cell
      count was significantly lower in men with ED as compared with men without ED
      (63.1 +/- 4 vs. 92.4 +/- 6 cells/10(6) events, mean +/- standard error, P <
      0.01). There was a significant direct correlation between circulating
      CD34(+)KDR(+) cells and the IIEF score (r = 0.44; P = 0.01): men with the severe
      form of ED presented the lowest level of circulating EPC CD34(+)KDR(+) cells. No
      significant correlation was found between the circulating levels of the other EPC
      phenotypes and the IIEF score. There was a significant correlation between
      CD34(+)KDR(+) cell count and FMD (r = 0.45; P = 0.01), but not between FMD and
      the other phenotypes. CONCLUSIONS: Circulating levels of CD34(+)KDR(+) EPC are
      reduced in overweight subjects with ED and correlate with the severity of ED.
      Other EPC phenotypes are not related to ED, suggesting that the CD34(+)KDR(+)
      phenotype of EPCs may be preferred in future studies.

PMID- 19170843
TI  - Role of the neurokinin-1 receptors in ejaculation in anesthetized rats.
AB  - INTRODUCTION: Several lines of evidence indicate a role for substance P in the
      control of ejaculation, although its mode of action needs to be clarified. AIM:
      The effects and sites of action of a selective antagonist for the substance P
      preferred receptor (neurokinin-1 receptor subtype; NK1) were investigated in a
      pharmacological model of ejaculation. METHODS: Ejaculation was induced in
      anesthetized rats by intracerebroventricular (i.c.v.) delivery of the dopamine D3
      receptor preferring agonist 7-hydroxy-2-(di-N-propylamino)tetralin (7-OH-DPAT).
      The effects of the selective NK1 antagonist RP67580 on 7-OH-DPAT-induced
      ejaculation were measured following intraperitoneal (i.p.), i.c.v., or
      intrathecal (i.t.) (third lumbar spinal segment; L3) administration. MAIN OUTCOME
      MEASURES: Intraseminal vesicle pressure (SVP) and electromyogram of the
      bulbospongiosus muscle (BS) were recorded as physiological markers of emission
      and expulsion phases of ejaculation, respectively. RESULTS: Upon i.p., i.c.v., or
      i.t. administration, RP67580 significantly reduced the occurrence of ejaculation
      elicited by 7-OH-DPAT. A mild decrease in the occurrence of SVP and BS responses
      was observed in rats treated ip with RP67580, whereas only SVP responses were
      moderately affected following i.c.v. or i.t. administration. CONCLUSION: These
      results show the multilevel regulation of 7-OH-DPAT-induced ejaculation by NK1
      receptors.

PMID- 19170842
TI  - TNF-alpha knockout mice have increased corpora cavernosa relaxation.
AB  - INTRODUCTION: Erectile dysfunction is considered an early clinical manifestation
      of vascular disease and an independent risk factor for cardiovascular events
      associated with endothelial dysfunction and increased levels of pro-inflammatory
      cytokines. Tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine,
      suppresses endothelial nitric oxide synthase (eNOS) expression. AIM: Considering
      that nitric oxide (NO) is of critical importance in penile erection, we
      hypothesized that blockade of TNF-alpha actions would increase cavernosal smooth
      muscle relaxation. METHODS: In vitro organ bath studies were used to measure
      cavernosal reactivity in wild type and TNF-alpha knockout (TNF-alpha KO) mice and
      NOS expression was evaluated by western blot. In addition, spontaneous erections
      (in vivo) were evaluated by videomonitoring the animals (30 minutes). Collagen
      and elastin expression were evaluated by Masson trichrome and Verhoff-van Gieson
      stain reaction, respectively. MAIN OUTCOME MEASURES: Corpora cavernosa from TNF
      alpha KO mice exhibited increased NO-dependent relaxation, which was associated
      with increased eNOS and neuronal NOS (nNOS) cavernosal expression. RESULTS:
      Cavernosal strips from TNF-alpha KO mice displayed increased endothelium
      dependent (97.4 +/- 5.3 vs. CONTROL: 76.3 +/- 6.3, %) and nonadrenergic
      noncholinergic (93.3 +/- 3.0 vs. CONTROL: 67.5 +/- 16.0; 16 Hz) relaxation
      compared to control animals. These responses were associated with increased
      protein expression of eNOS and nNOS (P < 0.05). Sympathetic-mediated (0.69 +/-
      0.16 vs. CONTROL: 1.22 +/- 0.22; 16 Hz) as well as phenylephrine-induced
      contractile responses (1.6 +/- 0.1 vs. CONTROL: 2.5 +/- 0.1, mN) were attenuated
      in cavernosal strips from TNF-alpha KO mice. Additionally, corpora cavernosa from
      TNF-alpha KO mice displayed increased collagen and elastin expression. In vivo
      experiments demonstrated that TNF-alpha KO mice display increased number of
      spontaneous erections. CONCLUSION: Corpora cavernosa from TNF-alpha KO mice
      display alterations that favor penile tumescence, indicating that TNF-alpha plays
      a detrimental role in erectile function. A key role for TNF-alpha in mediating
      endothelial dysfunction in ED is markedly relevant since we now have access to
      anti-TNF-alpha therapies.

PMID- 19170844
TI  - Women's partnered orgasm consistency is associated with greater duration of
      penile-vaginal intercourse but not of foreplay.
AB  - INTRODUCTION: It has been asserted that women's likelihood or consistency of
      partnered orgasm (her orgasm as a result of sexual activities with a partner) is
      determined by duration of foreplay, but not by duration of penile-vaginal
      intercourse. AIMS: The objective was to examine the extent to which women's
      likelihood or consistency of partnered orgasm is associated with duration of
      foreplay, duration of penile-vaginal intercourse, and age. METHODS: In a
      representative sample of the Czech population, 2,360 women reported their
      consistency of orgasm with a partner (from "never" to "almost every time"), and
      estimates of their typical durations of foreplay and of penile-vaginal
      intercourse. MAIN OUTCOME MEASURES: The association of consistency of partnered
      orgasm with typical durations of both foreplay and penile-vaginal intercourse.
      RESULTS: In univariate analyses, consistency of partnered orgasm was more
      associated with penile-vaginal intercourse duration than with foreplay duration
      (consistency also correlated negatively with age). In multivariate analysis,
      foreplay ceased to be a significant correlate of partnered orgasm consistency
      (the exclusion of respondents reporting a penile-vaginal intercourse duration of
      1 minute or less did not alter the results). CONCLUSIONS: When both sexual
      activity categories are examined in tandem on a population level, women's
      likelihood or consistency of partnered orgasm is associated with penile-vaginal
      intercourse duration, but not with foreplay duration. In contrast to the
      assumptions of many sex therapists and educators, more attention should be given
      to improve the quality and duration of penile-vaginal intercourse rather than
      foreplay.

PMID- 19170845
TI  - Sexual function: a comparison between male renal transplant recipients and
      hemodialysis patients.
AB  - INTRODUCTION: For all the studies into the sexual health of kidney transplant
      recipients, there is a paucity of controlled studies regarding the difference in
      the sexual relationship of kidney transplant recipients and end-stage renal
      disease (ESRD) patients under hemodialysis. AIM: We compared the sexual function
      of kidney transplant recipients and ESRD patients under hemodialysis in male
      patients. MAIN OUTCOME MEASURES: The patients' sexual function was assessed using
      the Relationship and Sexuality Scale. METHOD: In this case-controlled study, 89
      male renal transplant recipients and 25 male hemodialysis patients were randomly
      selected from the outpatient clinic of Baqiyatallah Hospital, Tehran, Iran, in
      2006. The two groups were not significantly different in terms of age, living
      place, level of education, duration of ESRD (months), ESRD cause, and somatic
      comorbidities (Ifudu index). RESULTS: The renal transplant patients in comparison
      with the hemodialysis group reported a better overall sexual relationship (17.3
      +/- 0.6 vs. 21.6 +/- 1.4; P = 0.001), and all subscales including sexual function
      (9.9 +/- 0.3 vs. 11.4 +/- 0.6; P = 0.03), sexual frequency (6.3 +/- 0.3 vs. 7.4
      +/- 0.6; P = 0.04), and sexual fear (1.1 +/- 0.2 vs. 2.8 +/- 0.5; P = 0.001). In
      addition, kidney recipients had significantly more sexual intercourse in a 2-week
      period prior to the study (P = 0.008). CONCLUSIONS: In our male population,
      kidney transplant recipients, in comparison with the ESRD patients under
      hemodialysis, reported a better sexual relationship.

PMID- 19170846
TI  - Association of sexual functioning and quality of partnership in patients in
      cardiovascular rehabilitation--a gender perspective.
AB  - INTRODUCTION: In the general population, studies indicate a strong association
      between sexual dysfunction and partnership quality. Despite a high prevalence of
      sexual problems in patients with cardiovascular diseases, this association has
      not yet been examined in this sample. AIM: The central task of this paper is to
      determine the association between sexual dysfunction and quality of partnership
      under a gender-specific view. METHODS: A written survey was handed out to all
      newly admitted patients in five participating inpatient rehabilitation centers
      for cardiovascular diseases in Germany. The survey included a gender-specific
      questionnaire to assess sexual functioning (International Index of Erectile
      Function for men, and Female Sexual Function Index for women), and a Partnership
      Questionnaire. MAIN OUTCOME MEASURES: Correlations were calculated between sexual
      function and relationship satisfaction, and differences between groups
      (cardiovascular diseased men and women with and without sexual problems) were
      tested using covariance analyses. RESULTS: Overall, 44.3% of 98 female
      participants and 52.7% of 395 male participants stated to have at least one
      sexual problem. Patients with sexual problems showed significantly more
      quarrelling (P = 0.001), significantly less tenderness (P < 0.001), communication
      (P < 0.001), as well as significantly lower overall quality of partnership (P <
      0.001), compared with cardiac men and women without sexual problems. Suffering
      from a sexual problem impaired partnership quality for women to a significantly
      greater extent than for men. CONCLUSIONS: Possible shortcomings of our study are
      selection bias, i.e., it is unknown whether all newly admitted patients received
      the questionnaire by their physician, as well as an overall low response rate,
      probably because of the private character of questions. This study suggests for
      the first time that men and women who suffer from cardiovascular diseases and
      sexual problems show a significantly decreased partnership satisfaction compared
      with those without sexual dysfunction. Further longitudinal studies might confirm
      the causal nature of found correlations.

PMID- 19170847
TI  - Clinically relevant changes in sexual desire, satisfying sexual activity and
      personal distress as measured by the profile of female sexual function, sexual
      activity log, and personal distress scale in postmenopausal women with hypoactive
      sexual desire disorder.
AB  - INTRODUCTION: Transdermal testosterone patch (TTP) treatment produced
      statistically significant improvements in a satisfying sexual activity (SSA),
      sexual desire, and personal distress in postmenopausal women suffering from
      hypoactive sexual desire disorder (HSDD), but clinical significance of these
      changes was not determined. AIM: To quantify the magnitude of change in three
      principal outcomes measures determined by HSDD patients as associated with the
      perception of meaningful benefit with TTP therapy. METHODS: The criteria for
      defining responders were determined using anchoring methodology and receiver
      operating characteristics analysis to establish minimum important differences
      (MIDs) in a representative subsample of 132 patients in two randomized,
      controlled trials in surgically menopausal women with HSDD (N = 1,094). Perceived
      benefit was established based upon the question "Overall, would you say that you
      experienced a meaningful benefit from the study patches?". These data defined
      responders and established MIDs for changes in sexual desire, SSA, and personal
      distress. The MIDs were applied to the two trials to establish responder rates in
      each treatment group. MAIN OUTCOME MEASURES: Changes in score that correspond to
      the MID for sexual desire, SSA, and personal distress, and responder rates in
      each treatment group based upon these values. RESULTS: Increases in frequency of
      SSA of greater than 1 activity/4 weeks, increases in sexual desire score of > or
      = 8.9, and decreases in the personal distress score of > or = 20.0 were
      identified as threshold improvements best able to differentiate responders and
      nonresponders. The responder rate was significantly higher (P < 0.001) in the
      testosterone group vs. placebo for all three outcomes measures (sexual desire,
      50% vs. 34%; SSA, 44% vs. 30%; personal distress, 51% vs. 39%). CONCLUSIONS:
      Changes in sexual desire, SSA, and personal distress observed with TTP treatment
      in surgically menopausal women with HSDD were clinically significant and were
      associated with a meaningful treatment benefit.

PMID- 19170848
TI  - Vaginismus and accompanying sexual dysfunctions in a Turkish clinical sample.
AB  - INTRODUCTION: Although vaginismus is a common sexual dysfunction in Turkey, there
      are only limited data about sexual behavior characteristics and comorbidity with
      other sexual dysfunctions in vaginismic patients. AIM: To investigate the
      frequency of female sexual dysfunctions (FSDs) in a Turkish clinical sample and
      to determine the comorbidity of other FSDs in women diagnosed with lifelong
      vaginismus. METHODS: The study included 54 female patients who presented to a
      psychiatry department with sexual problems/complaints. MAIN OUTCOME MEASURES: The
      subjects were evaluated using a semi-structured questionnaire. The questionnaire
      was developed by the researchers in order to assess sexually dysfunctional
      patients and included detailed questions about socio-demographic variables, and
      general medical and sexual history. All participants were also assessed using the
      Golombok Rust Inventory of Sexual Satisfaction. RESULTS: The most common primary
      FSD in our sample was vaginismus (75.9%), followed by hypoactive sexual desire
      (9.2%). Regarding comorbidity, in 36 female patients with lifelong vaginismus, we
      found dyspareunia in 17 women (47.2%), orgasmic disorder in eight women (22.2%),
      and sexual desire disorder in six women (16.6%) as a second sexual dysfunction,
      based on the Diagnostic and Statistical Manual of Mental Disorders-Fourth
      Edition, Text Revision criteria. CONCLUSIONS: With respect to FSDs within the
      Turkish clinical population, vaginismic patients constitute the largest group and
      cultural factors may play a role in the occurrence of this condition.
      Additionally, our data indicated that there was a strong correlation between
      vaginismus and dyspareunia. There was also a high frequency of hypoactive desire
      and orgasm disorder in vaginismic patients. These results suggest that
      multidimensional assessment of sexual dysfunction in female patients is of great
      importance.

PMID- 19170849
TI  - Multiple pelvic floor complaints are correlated with sexual abuse history.
AB  - INTRODUCTION: The relationship between sexual abuse and urinary tract symptoms,
      sexual abuse and gastrointestinal symptoms, or sexual abuse and sexual
      dysfunction has been described before. A correlation between all these symptoms
      and sexual abuse has not yet been reported. AIMS: The first aim of this study was
      to document the prevalence rates of reported sexual abuse in a large sample of
      female patients with complaints of the pelvic floor. The second aim was to
      evaluate the frequency of complaints in the different domains of the pelvic
      floor, such as complaints of micturition, defecation, and sexual function, in
      female patients reporting sexual abuse, and comparing these data with female
      patients without a history of sexual abuse. METHODS: Female patients with pelvic
      floor complaints were evaluated in a tertiary referral center. History taking was
      assessed by a pelvic-floor clinician. The number of domains with complaints of
      patients with a history of sexual abuse was compared with the number of domains
      with complaints of patients without sexual abuse. MAIN OUTCOME MEASURES: The
      number of patients who reported sexual abuse and the frequency of complaints in
      the different domains of the pelvic floor. The number of domains of patients with
      a history of sexual abuse was compared with patients without a history of sexual
      abuse. RESULTS: Twenty-three percent (42/185) of the patients reported a history
      of sexual abuse. The female patients with a history of sexual abuse had
      significantly more complaints in three domains of the pelvic floor (35/42)
      compared with the nonabused (69/143) (83% vs. 48%, P < 0.001). CONCLUSIONS:
      Twenty-three percent of the female patients in a pelvic floor center evaluated by
      a pelvic-floor clinician reported a history of sexual abuse. This is comparable
      with the percentage of sexual abuse observed in the population at large. In our
      sample, the patients with multiple pelvic floor complaints (micturition,
      defecation, and sexual function) related to pelvic floor dysfunction were more
      likely to have a history of sexual abuse than the patients with isolated
      complaints.

PMID- 19170850
TI  - Pain, psychosocial, sexual, and psychophysical characteristics of women with
      primary vs. secondary provoked vestibulodynia.
AB  - INTRODUCTION: Women with provoked vestibulodynia (PVD), a common cause of
      dyspareunia, are typically considered a homogeneous group. However, research
      suggests that differences on some factors (e.g., medical history, pain
      characteristics, psychological functioning, treatment response) exist based upon
      whether the pain was present at first intercourse (primary PVD: PVD1) or
      developed at some later point (secondary PVD: PVD2). AIMS: The purpose of this
      study was to examine differences in demographic variables, pain characteristics,
      psychosocial and psychosexual adjustment, and pain sensitivity between women with
      PVD1 and PVD2. METHODS: Twenty-six women suffering from PVD (13 with PVD1 and 13
      with PVD2) completed a screening assessment, a standardized gynecological
      examination, an interview, questionnaires, and a quantitative sensory testing
      session. MAIN OUTCOME MEASURES: These included pain ratings during the
      gynecological examination and interview, scores on measures of
      psychosocial/sexual functioning (e.g., Short Form-36 [SF-36] Health Survey,
      Female Sexual Function Index), and thresholds and pain ratings during thermal
      sensory testing over the dominant forearm and vulvar vestibule. RESULTS: The
      women with PVD1 were more likely to be nulliparous, but they were not
      significantly different from the women with PVD2 on other demographic variables
      or in their pain ratings during the gynecological examination. The women with
      PVD1 reported lower levels of social and emotional functioning and heightened
      anxiety surrounding body exposure during sexual activity, and they also displayed
      lower heat pain tolerance over the forearm and lower heat detection and pain
      thresholds at the vulvar vestibule than the women with PVD2. CONCLUSIONS: The
      findings from this study support previous research indicating that women with
      PVD1 and PVD2 differ in a number of domains. Further research is needed to
      confirm and elaborate on these findings.

PMID- 19170851
TI  - Persistent genital and pelvic pain after childbirth.
AB  - INTRODUCTION: Although genital pain and pelvic pain are common and well
      documented problems in the early postpartum period, little is known about their
      course. The few published studies of such pain beyond 1 year postpartum have
      focused primarily on the perineum and have not assessed pain onset. AIM: To
      investigate the prevalence and characteristics of all types of genital and pelvic
      pain in the second year postpartum, and to explore risk factors for their
      persistence. METHODS: Over a 6-month period, a questionnaire on genital/pelvic
      pain, sociodemographic and childbirth variables, breastfeeding, and chronic pain
      history was mailed to patients of the collaborating obstetrician at 12 months
      postpartum. MAIN OUTCOME MEASURES: The prevalence, characteristics, and
      correlates of persistent genital/pelvic pain with postpartum onset. RESULTS:
      Almost half of the 114 participants (82% response rate; M = 14 months postpartum)
      reported a current (18%) or resolved (26%) episode of genital or pelvic pain
      lasting 3 or more months. Just under one in 10 (9%) mothers continued to
      experience pain that had begun after they last gave birth. This pain was
      described at various locations (e.g., vaginal opening and pelvic area), as
      moderate in intensity and unpleasantness, and most often as burning, cutting, or
      radiating. Although it was triggered by both sexual and nonsexual activities,
      none of the mothers affected were receiving treatment. Univariate analyses
      revealed that only past diagnosis with a nongenital chronic pain condition (e.g.,
      migraine headache) was significantly correlated with (i) any history of chronic
      genital/pelvic pain or (ii) the persistence of pregnancy- or postpartum-onset
      genital or pelvic pain. CONCLUSIONS: Postpartum genital and pelvic pain persists
      for longer than a year for a significant percentage of mothers. Women with a
      history of other chronic pain appear to be particularly vulnerable to developing
      persistent genital or pelvic pain.

PMID- 19170852
TI  - Aspects of sexual satisfaction in men with erectile dysfunction: a factor
      analytic and logistic regression approach.
AB  - INTRODUCTION: The International Index of Erectile Function (IIEF), Sexual
      Encounter Profile (SEP), and Erectile Dysfunction Inventory of Treatment
      Satisfaction (EDITS) assess efficacy of phosphodiesterase type 5 (PDE5) inhibitor
      treatment of erectile dysfunction (ED). AIMS: To determine the degree that
      multiplicity of satisfaction questions in ED treatment evaluation instruments are
      congruent, to better understand the concept of sexual "satisfaction," and to
      identify factors that correlate with improvement. METHODS: Questionnaire data
      from 4,174 placebo- or tadalafil-treated patients with ED were analyzed.
      Principal component analysis (PCA) was performed on IIEF and SEP satisfaction
      questions. Spearman correlation coefficients were determined. Data from 431 of
      the 4,174 patients who completed EDITS questionnaires were analyzed. Logistic
      regression was used to investigate improvement of each IIEF satisfaction
      question. RESULTS: PCA rotated on three factors explained 91% of total variance
      and separated IIEF Q6 (intercourse frequency) from a SEP and a remaining IIEF
      factor. All correlations between and among questions were close (rho = 0.62-0.98;
      P < 0.0001), except for those with IIEF Q6 (rho = 0.28-0.34; P < 0.0001). In a
      sub-sample, PCA of five IIEF, two SEP, and three EDITS questions identified four
      factors that explained 90% of all variance: EDITS questions, IIEF questions
      except Q6, SEP questions, and IIEF Q6. Greater improvement in IIEF-EF domain
      score was consistently and positively associated with satisfaction measures (P <
      0.0001). CONCLUSIONS: Factor analysis detected close relationships among
      satisfaction questions in IIEF, SEP, and EDITS instruments, each of which, apart
      from IIEF Q6 (intercourse frequency), appeared to be an independent measure of
      satisfaction. Cultural differences may explain different satisfaction
      correlations with baseline ED severity in different regions. Clinicians may make
      use of the correlation between intercourse frequency (Q6) and satisfaction when
      prescribing a PDE5 inhibitor for ED, by explaining that the inhibitor should
      enable more frequent intercourse.

PMID- 19170853
TI  - Effects of intensive lifestyle changes on erectile dysfunction in men.
AB  - INTRODUCTION: Limited data are available supporting the notion that treatment of
      lifestyle risk factors may improve erectile dysfunction (ED). AIM: In the present
      study, we analyzed the effect of a program of changing in lifestyle designed to
      improve erectile function in subjects with ED or at increasing risk for ED.
      METHODS: Men were identified in our database of subjects participating in
      randomized controlled trials evaluating the effect of lifestyle changes. A total
      of 209 subjects were randomly assigned to one of the two treatment groups. The
      104 men randomly assigned to the intervention program received detailed advice
      about how to reduce body weight, improve quality of diet, and increase physical
      activity. The 105 subjects in the control group were given general information
      about healthy food choices and general guidance on increasing their level of
      physical activity. MAIN OUTCOME MEASURES: Changes in erectile function score
      (International Index of Erectile Function-5 [IIEF-5]; items 5, 15, 4, 2, and 7
      from the full-scale IIEF-15) and dependence of the restoration of erectile
      function on the changes in lifestyle that were achieved. RESULTS: Erectile
      function score improved in the intervention group. At baseline, 35 subjects in
      the intervention group and 38 subjects in the control group had normal erectile
      function (34% and 36%, respectively). After 2 years, these figures were 58
      subjects in the intervention group and 40 subjects in the control group,
      respectively (56% and 38%, P = 0.015). There was a strong correlation between the
      success score and restoration of erectile function. CONCLUSIONS: It is possible
      to achieve an improvement of erectile function in men at risk by means of
      nonpharmacological intervention aiming at weight loss and increasing physical
      activity.

PMID- 19170854
TI  - Evaluation of patient expectations and treatment satisfaction after 1-year
      tadalafil therapy for erectile dysfunction: the DETECT study.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a self-reported condition and
      satisfaction with sexual performance is individual, subjective, and multi
      factorial. Treatment success depends on several outcomes. Tadalafil is a long
      acting, selective inhibitor of phosphodiesterase 5 that has been shown to be
      effective at treating men with ED. AIM: To investigate patient's ED treatment
      expectations at baseline; patient satisfaction with tadalafil treatment after 12
      months; factors associated with satisfaction; and effect of early tadalafil
      treatment satisfaction on tadalafil continuation at 12 months. METHODS: The
      Determinants of Continued Use of Tadalafil study is a 12-month, prospective, pan
      European, noninterventional, observational study, which enrolled 1,900 patients
      with ED wishing to initiate or change their treatment to tadalafil. Assessments
      were made on predefined treatment outcomes in a routine clinical setting. MAIN
      OUTCOME MEASURES: International Index of Erectile Function-erectile function
      domain scores (at baseline, 1, 6, and 12 month visit), ED Inventory of Treatment
      Satisfaction (EDITS) scores (after 1, 6, and 12 months), and patient expectation
      questionnaire (at baseline visit) were analyzed for these patients. RESULTS: Data
      were available from 1,567 patients (82%) after 12 months, with similar baseline
      characteristics as the initial cohort. Treatment expectations identified as
      important included: erection hardness and ability to maintain erection through
      intercourse completion (>92% of patients); confidence, partner satisfaction, and
      naturalness (>84% of patients); rapid effect and long duration of treatment (>75%
      of patients). Continued tadalafil use from 1,319 (84%) patients at 12 months were
      reported. Total EDITS scores for those continuing treatment was 85.9 (95% CI:
      85.1-86.7). Increased satisfaction was associated with higher effectiveness,
      number of sexual attempts, partner support, good relationships, and good drug
      tolerance. Treatment satisfaction at 1 month was best predictive of treatment
      continuation at 12 months. CONCLUSIONS: Eighty-four percent of patients reported
      continued use of tadalafil after 12 months. High satisfaction after first month
      of treatment was the best predictor of treatment continuation.

PMID- 19170855
TI  - Serotonin transporter promoter region (5-HTTLPR) polymorphism is associated with
      the intravaginal ejaculation latency time in Dutch men with lifelong premature
      ejaculation.
AB  - INTRODUCTION: Lifelong premature ejaculation (LPE) is characterized by persistent
      intravaginal ejaculation latency times (IELTs) of less than 1 minute, and has
      been postulated as a neurobiological dysfunction with genetic vulnerability for
      the short IELTs, related to disturbances of central serotonin (5
      hydroxytryptamine [5-HT]) neurotransmission and 5-HT receptor functioning. AIM:
      To investigate the relationship between 5-HT transporter gene-linked polymorphism
      (5-HTTLPR) and short IELTs in men with lifelong PE. METHODS: A prospective study
      was conducted in 89 Dutch Caucasian men with lifelong PE. IELT during coitus was
      assessed by stopwatch over a 1-month period. Controls consisted of 92 Dutch
      Caucasian men. All men with LPE were genotyped for a 5-HTT-promoter polymorphism.
      Allele frequencies and genotypes of short (S) and long (L) variants of 5-HTTLPR
      polymorphism were compared between patients and controls. Association between LL,
      SL, and SS genotypes, and the natural logarithm of the IELT in men with LPE was
      investigated. MAIN OUTCOME MEASURES: IELT measured by stopwatch, 5-HTTLPR
      polymorphism. RESULTS: In men with lifelong PE, the geometric mean, median, and
      natural mean IELTs were 21, 26, and 32 seconds, respectively. There were no
      significant differences in the 5-HTT polymorphism alleles and genotypes between
      89 Dutch Caucasian men with LPE (S 47%, L 53%/LL 29%, SL 48%, SS 22%) and 92
      Dutch Caucasian controls (S 48%, L 52%/LL 29%, SL 45%, SS 26%). In men with
      lifelong PE there was a statistically significant difference between LL, SL, and
      SS genotypes in their geometric mean IELT (P < or = 0.027); the LL genotypes had
      significantly shorter IELTs than the SS and SL genotypes. CONCLUSIONS: The 5
      HTTLPR polymorphism is associated with significant effects on the latency to
      ejaculate in men with lifelong PE. Men with SS and SL genotypes have 100% and 90%
      longer ejaculation time, respectively than men with LL genotypes.

PMID- 19170856
TI  - Pulse pressure, an index of arterial stiffness, is associated with androgen
      deficiency and impaired penile blood flow in men with ED.
AB  - INTRODUCTION: Pulse pressure (PP; i.e., the arithmetic difference between
      systolic and diastolic blood pressure) reflects arterial stiffness and has been
      suggested to be an independent cardiovascular risk factor. AIM: The aim of the
      present study is to asses the possible contribution of PP to arteriogenic
      erectile dysfunction (ED) and ED-associated hypogonadism. METHODS: A consecutive
      series of 1,093 (mean age 52.1 +/- 13.0 years) male patients with ED and without
      a previous history of hypertension or not taking any antihypertensive drugs were
      investigated. MAIN OUTCOME MEASURES: Several hormonal and biochemical parameters
      were studied, along with structured interview on erectile dysfunction (SIEDY),
      ANDROTEST structured interviews, and penile Doppler ultrasound. RESULTS: Subjects
      with higher PP quartiles showed worse erectile function and higher prevalence of
      arteriogenic ED even after adjustment for confounding factors. Furthermore, sex
      hormone binding globulin-unbound testosterone levels declined as a function of PP
      quartiles. Accordingly, the prevalence of overt hypogonadism (calculated free
      testosterone < 180 pmol/L or free testosterone < 37 pmol/L) increased as a
      function of PP quartiles (17.% vs. 39.7%, and 30.8% vs. 58.6% for the first vs.
      fourth quartile, respectively, for calculated free testosterone and free
      testosterone; all P < 0.0001 for trend). This association was confirmed even
      after adjustment for confounders (Adjusted [Adj]) r = 0.090 and 0.095 for
      calculated free testosterone < 180 pmol/L and free testosterone < 37 pmol/L,
      respectively; all P < 0.05). CONCLUSIONS: PP is an easy method to estimate and
      quantify patient arterial stiffness. We demonstrated here for the first time that
      elevated PP is associated with arteriogenic ED and male hypogonadism. The
      calculation of PP should became more and more familiar in the clinical practice
      of health care professionals involved in sexual medicine.

PMID- 19170858
TI  - Microbial inactivation using plasma-activated water obtained by gliding electric
      discharges.
AB  - AIM: To evaluate the microbial disinfection efficacy of a plasmachemical solution
      obtained by the activation of water with gliding electric discharges. METHODS AND
      RESULTS: Distilled water was activated for 5 min by a nonthermal quenched plasma
      of the glidarc type operating in humid air and at atmospheric pressure. The
      plasma-activated water (PAW) was then used to treat planktonic and adherent cells
      of Staphylococcus epidermidis, Leuconostoc mesenteroides (as models of Gram
      positive bacteria), Hafnia alvei (a Gram-negative bacteria) and Saccharomyces
      cerevisiae (as a yeast model). The treatments were less efficient on adherent
      cells than on planktonic cells in the case of bacteria, but not of S. cerevisiae.
      Inactivation was more effective for bacteria than for the yeast. CONCLUSIONS:
      Significant reductions in microbial populations were achieved in all cases,
      demonstrating the effectiveness of this new approach to treat contaminated media.
      SIGNIFICANCE AND IMPACT OF THE STUDY: PAW is a promising solution with potential
      application to the decontamination of equipment and surfaces.

PMID- 19170860
TI  - Beneficial impact of exercise and obesity interventions on erectile function and
      its risk factors.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a multifaceted disease involving
      cardiovascular, metabolic, and hormonal factors and affects over 100 million men
      worldwide. ED has been shown to be a harbinger of underlying cardiovascular
      diseases (CVD), as there are common risk factors (aging, hypertension, obesity)
      and mechanistic basis. AIM: To provide an update on clinical and experimental
      evidence regarding the impact of lifestyle modifications, such as exercise and
      diet, with respect to changes in erectile function. MAIN OUTCOME MEASURES:
      Published evidence regarding the impact of aging, hypertension, and obesity on ED
      and CVD, as well as new experimental data linking obesity and diminished erectile
      responses. METHODS: We reviewed the literature regarding common risk factors of
      ED and CVD, particularly involving obesity, as well as performed new analysis on
      the findings of other experimental studies involving diet and exercise
      interventions. RESULTS: Physical inactivity negatively impacts on erectile
      function, and experimental and clinical exercise interventions have been shown to
      improve sexual responses and overall cardiovascular health. Mediterranean-style
      diets and a reduction in caloric intake have been found to improve erectile
      function in men with the aspects of the metabolic syndrome. In addition, both
      clinical and experimental studies have confirmed that combining the two
      interventions provides additional benefit to erectile function, likely via
      reduced metabolic disturbances (e.g., inflammatory markers, insulin resistance),
      decreased visceral adipose tissue, and improvement in vascular function (e.g.,
      increased endothelial function). CONCLUSIONS: Lifestyle modifications provide
      significant benefits to vascular health and erectile function in a population
      that is increasingly aged and more obese.

PMID- 19170861
TI  - Erectile dysfunction might be associated with chronic periodontal disease: two
      ends of the cardiovascular spectrum.
AB  - INTRODUCTION: Both chronic periodontal disease (CPD) and erectile dysfunction
      (ED) are associated with cardiovascular disease and its risk factors, including
      smoking and diabetes mellitus. However, the association between ED and CPD has
      never been studied. AIM: To study the association between ED and CPD. MAIN
      OUTCOME MEASURES. Prevalence of ED, prevalence of CPD, ED severity. METHODS: The
      study population consisted of 305 men who filled the Sexual Health Inventory for
      Men (SHIM) questionnaire in order to detect ED and assess its severity, and
      underwent a pair of standardized posterior dental bitewing radiographs in order
      to detect CPD. SHIM questionnaire scores 21 or less represented ED. Alveolar bone
      loss of >or=6 mm represented CPD. RESULTS: The mean age of included men was 39.5
      +/- 6.7 years. Overall, 70 (22.9%) men had ED and 13 (4.3%) had CPD. CPD was
      significantly more prevalent among men with mild ED (P = 0.004) and moderate to
      severe ED (P = 0.007) in comparison to men without ED. CONCLUSIONS: ED might be
      associated with CPD. These preliminary findings are consistent with theories that
      associate these conditions with systemic inflammation, endothelial dysfunction,
      and atherosclerosis.

PMID- 19170862
TI  - "Just relax": physicians' experiences with women who are difficult or impossible
      to examine gynecologically.
AB  - INTRODUCTION: The internal pelvic exam is a critical component of women's
      reproductive health care; however, it can be perceived as uncomfortable,
      embarrassing, and painful, which may lead some women to avoid this procedure.
      AIMS: The purpose of this study was to survey physicians with respect to their
      experiences with female patients who are difficult or impossible to examine
      gynecologically. METHODS: Six hundred and fifty-eight obstetrician-gynecologist
      and family physicians were sent a 15-item questionnaire by mail and 424
      participants responded (64% response rate). The survey consisted of questions
      pertaining to demographic variables, professional training and practice
      information, the frequency with which they encounter female patients who are
      difficult or impossible to examine, and the strategies employed with and beliefs
      surrounding such patients. MAIN OUTCOME MEASURES: The main outcome measures were
      the frequency of patients who are difficult or impossible to examine, strategies
      used to manage such patients, and beliefs as to why these patients are difficult
      or impossible to examine. RESULTS: The results, based on a final sample size of
      401, indicated that most respondents have had some experience with patients who
      are difficult or impossible to examine. In such cases, most physicians (87%)
      reported attempting to address their patients' lack of relaxation. The majority
      of physicians in this study believed that a previous negative experience with
      (87%), and heightened anxiety about (79%), the exam were to blame. Twelve percent
      of respondents specifically reported that a previous history of sexual abuse was
      an important factor. CONCLUSIONS: This study reinforces the importance of being
      aware of patient discomfort during pelvic exams and of developing strategies that
      fit the individual patient and her needs. Future research should examine women's
      perceptions of their reproductive care, particularly correlates of pain and
      anxiety during pelvic exams, prevalence of negative experiences, and doctor
      patient interactions in this context.

PMID- 19170863
TI  - Beyond douching: use of feminine hygiene products and STI risk among young women.
AB  - INTRODUCTION: Use of feminine hygiene products (feminine wipes, sprays, douches,
      and yeast creams) by adolescent women is common, yet understudied. AIM: We
      examine the association among these genital hygiene behaviors, condom use, and
      sexually transmitted infection (STI). MAIN OUTCOME MEASURES: Using the interview
      as our unit of analysis, we examined associations between genital hygiene
      behaviors (use of feminine wipes, feminine sprays, douches, or yeast creams), STI
      risk factors, and infection with Chlamydia trachomatis, Neisseria gonorrhoeae,
      and Trichomonas vaginalis. METHODS: We recruited 295 adolescent women from
      primary care clinics as part of a larger longitudinal study of STI among high
      risk adolescents. Participants completed face-to-face interviews every 3 months,
      and provided vaginal swabs for STI testing. Data were analyzed with repeated
      measures logistic models to control for multiple observations contributed by each
      participant. RESULTS: Participants reported douching in 25% of interviews,
      feminine sprays in 29%, feminine wipes in 27%, and yeast creams in 19% of
      interviews. We observed a co-occurrence of douching, spraying, and wiping. A past
      STI (6 months or more prior) was associated with increased likelihood of yeast
      cream use, and a recent STI (3 months prior) was associated with increased
      likelihood of feminine wipe use. Condom use was modestly associated with
      increased likelihood of douching. CONCLUSIONS: Young women frequently use
      feminine hygiene products, and it is important for clinicians to inquire about
      use as these products may mimic or mask STI. We found no associations between
      douching and STI, but instead modest associations between hygiene and STI
      prevention, suggesting motivation for self-care.

PMID- 19170864
TI  - Neuropeptide modulation of a lumbar spinal reflex: potential implications for
      female sexual function.
AB  - INTRODUCTION: Neuropeptides are known to modulate female receptivity. However,
      even though receptivity is a spinal reflex, the role of neuropeptides within the
      spinal cord remains to be elucidated. AIM: The aims were to (i) investigate
      neuropeptides in the lumbosacral region; and (ii) determine how neuropeptides
      modulate glutamate release from stretch Ia fibers, touch sensation Abeta fibers
      and Adelta/C pain fibers. MAIN OUTCOME MEASURES: Neuropeptide modulation of the
      lumbosacral dorsal-root ventral-root reflex in vitro. METHODS: Spinal cords were
      removed from Sprague-Dawley rats in compliance with UK Home Office guidelines.
      Hemisected cords were superfused with aCSF and the dorsal root (L4-S1) was
      stimulated to evoke glutamate release. A biphasic reflex response was evoked from
      the opposite ventral root consisting of a monosynaptic (Ia fibers) and
      polysynaptic (Abeta, Adelta/C fibers) component. RESULTS: The micro opioid
      receptor (MOR) agonist DAMGO inhibited the monosynaptic (EC(50) 0.02 +/- 0.02 nM)
      and polysynaptic area (EC(50) 125 +/- 167 nM) but not polysynaptic amplitude.
      Oxytocin and corticotrophin releasing factor (CRF) inhibited the monosynaptic
      amplitude (EC(50), 1.4 +/- 1.0 nM and EC(50) 4.3 +/- 3.5 nM, respectively),
      polysynaptic amplitude (EC(50) 18.2 +/- 28.0 nM and EC(50), 9.5 +/- 13.3 nM,
      respectively), and area (EC(50) 11.6 +/- 13.0 nM and EC(50), 2.8 +/- 3.3 nM,
      respectively); effects that were abolished by oxytocin and CRF(1) antagonists, L
      368899 and 8w. Melanocortin agonists solely inhibited the monosynaptic component,
      which were blocked by the MC(3/4) receptor antagonist SHU9119. CONCLUSION: These
      data suggest endogenous neuropeptides are released within the lumbosacral spinal
      cord. Melanocortin agonists, oxytocin, CRF, and DAMGO via MC(4), oxytocin,
      CRF(1), and MOR inhibit glutamate release but with differing effects on afferent
      fiber subtypes. Melanocortins, oxytocin, CRF, and DAMGO have the ability to
      modulate orgasm whereas oxytocin, CRF and DAMGO can increase pain threshold.
      Oxytocin and CRF may dampen touch sensation.

PMID- 19170865
TI  - Revealing the buried penis in adults.
AB  - INTRODUCTION: Several surgical solutions have been proposed for resolving penile
      concealment with successful outcomes. Those include liposuction, adhesiolysis,
      and suprapubic lipectomy through the abdominal crease. Nevertheless, some
      limitations exist and compromise the results of surgical correction. AIM: This
      work presents our technique for revealing the hidden penis, addressing the
      limitations of existing methods for surgical correction. METHODS: Sixty-four
      adult males with buried penis were operated upon. The penis was revealed by the
      combination of adhesiolysis, suprapubic and lateral lipectomy, anchoring the
      penoscrotal and penopubic junctions, and skin coverage by a local flap. MAIN
      OUTCOME MEASURES: Penile length in the flaccid and erect states. RESULTS: Average
      postoperative length in the flaccid state was approximately 7 cm +/- 1.3 (a 293%
      increase) and in the erect state was 18.4 cm +/- 2.9 (185.7% increase), compared
      with preoperative length of 1.8 cm +/- 0.4 in the flaccid state and 6.4 cm +/-
      1.6 in the erect state. Minor complications occurred. There was no deterioration
      in sexual function. CONCLUSION: Revealing the concealed penis is a complicated
      procedure. The outcome may be improved by implementing a radical approach to
      tissue excision, providing adequate skin coverage, and anchoring the penile
      shaft, skin, and subcutaneous tissues in the revealed state to prevent relapse.

PMID- 19170866
TI  - Self-reported sexual difficulties and their association with depression and other
      factors among gay men attending high HIV-caseload general practices in Australia.
AB  - INTRODUCTION: Sexual expression affects physical, mental and social well-being.
      There is a lack of understanding of male sexual dysfunction in homosexually
      active men. Aim. We investigated gay men's self-report of a number of sexual
      problems. METHODS: The survey data were from a sample of 542 self-identified gay
      men, 40% of whom were HIV positive, recruited from six high HIV-caseload general
      practices in Australia. MAIN OUTCOME MEASURES: The reporting of experiencing
      three or more sexual problems over a period of at least 1 month in the 12 months
      prior to a survey was defined here as having "multiple" sexual problems. We
      explored a number of factors, including HIV status, depression, alcohol and other
      drug use, and sexual risk-taking with casual male partners, in association with
      multiple sexual problems. RESULTS: Rates of a range of self-reported sexual
      problems were high, with erectile dysfunction and lack of sexual desire being the
      most commonly reported. These high rates were consistent with the limited data
      from previous Australian studies. Men who had multiple sexual problems were
      likely to suffer from major depression (P < 0.001). A higher proportion of the
      HIV-positive gay men (48.4%) reported multiple sexual problems than the HIV
      negative men (35.1%, P = 0.002). Factors independently associated with multiple
      sexual problems among the HIV-negative gay men were poorer general health and
      interpersonal isolation, whereas for the HIV-positive gay men, they were adoption
      of avoidant strategies to cope with daily life stress, sexual risk-taking in
      casual encounters, and the use of antidepressants. CONCLUSIONS: Our findings
      underscore the complex interactions between depression, sexual dysfunction,
      sexual risk taking, HIV infection, and general well-being among homosexually
      active men.

PMID- 19170867
TI  - Vasculogenic erectile dysfunction is a predictor of abnormal stress
      echocardiography.
AB  - INTRODUCTION: Erectile dysfunction (ED) and atherosclerotic vascular disease have
      the same risk factors; furthermore, endothelial dysfunction has been shown to be
      a common link between these conditions. A high prevalence of silent coronary
      artery disease (CAD) in patients with ED has been observed. AIMS: The aims of
      this article were to define the prevalence and identify predictors of occult
      obstructive CAD in patients with documented vasculogenic ED. MAIN OUTCOME
      MEASURES: Duplex Doppler penile ultrasonography (DUS); exercise stress
      echocardiography; IIEF; CAD risk factors. Methods. Patients presenting with ED
      who had penile vascular insufficiency documented by DUS and who had no history of
      diabetes or symptoms of CAD were prospectively enrolled for noninvasive cardiac
      stress testing using exercise stress echocardiography. RESULTS: Forty-nine men
      (mean age 517 years) with an average duration of ED of 2.52 years were evaluated.
      Penile arterial insufficiency was present in 94%, and venous leak in 20% of
      patients. Comorbidities included hypertension (51%), hyperlipidemia (41%), and
      smoking (35%). All patients had at least one vascular risk factor, with 40%
      having two, 15% three, and 15% four risk factors. Ten patients (20%) had abnormal
      cardiac stress test. On univariate analysis, age, IIEF-EF domain score,
      cavernosal artery insufficiency, presence of venous leak, and history of a first
      degree relative with CAD were significant predictors. On multivariate analysis,
      cavernosal artery insufficiency, venous leak, and family history of CAD continued
      to be predictors of an abnormal stress test. CONCLUSIONS: A significant
      proportion of men with vasculogenic ED have abnormal cardiac stress test. The
      greatest chance for abnormal cardiac stress test was observed in those with
      corporo-venocclusive dysfunction or family history of CAD. In some men presenting
      with ED, even without a CAD history, performing penile DUS or cardiology referral
      for stress testing should be considered.

PMID- 19170868
TI  - Validation of the decreased sexual desire screener (DSDS): a brief diagnostic
      instrument for generalized acquired female hypoactive sexual desire disorder
      (HSDD).
AB  - INTRODUCTION: An accurate diagnosis of Hypoactive Sexual Desire Disorder (HSDD)
      currently relies on a time-consuming interview with an expert clinician. Limited
      access to such expertise means that many women with HSDD remain undiagnosed. The
      Decreased Sexual Desire Screener (DSDS) was developed to provide clinicians who
      are neither trained nor specialized in Female Sexual Dysfunction (FSD) with a
      brief diagnostic procedure for the diagnosis of generalized acquired HSDD in
      women. METHODS: A prospective non-treatment multicenter study enrolled 263 women
      at 27 centers in North America in order to test the validity of the DSDS for
      diagnosing generalized acquired HSDD in women. Subjects completed the DSDS at the
      screening visit and their answers were reviewed with a clinician who was not an
      expert in FSD ("non-expert clinician"). Separately and while being unaware of the
      non-expert clinician's diagnosis, an expert clinician conducted a standard
      diagnostic interview. MAIN OUTCOME MEASURES: Diagnostic outcomes (generalized
      acquired HSDD or not) were compared. Primary endpoints included the sensitivity
      and specificity of the DSDS relative to the standard diagnostic interview.
      Subject and non-expert clinician debriefing were obtained via a written,
      structured interview. This ensured that a large sample could be tested under
      uniform conditions across multiple sites. RESULTS: Diagnostic assessment by DSDS
      and standard diagnostic interview were in agreement in 85.2% (224/263) of cases,
      with the sensitivity and specificity of the DSDS 83.6% and 87.8%, respectively.
      Debriefing showed that the five DSDS questions were well understood by 85.4%
      (76/89) of subjects included in the debriefing exercise, while non-expert
      clinicians considered the DSDS questions adequate to diagnose HSDD in 92.9%
      (235/253) of cases. CONCLUSIONS: The DSDS is a sensitive and specific brief
      diagnostic instrument for generalized acquired HSDD in women that is quick and
      easy to use.

PMID- 19170869
TI  - HPV infection in women: psychosexual impact of genital warts and intraepithelial
      lesions.
AB  - INTRODUCTION: Genital Human Papillomavirus (HPV) infection is the most commonly
      occurring sexually transmitted viral infection in humans. HPV is a wide family of
      DNA viruses, which may cause benign skin and mucosal tumors (genital, anal, or
      oral warts), intraepithelial neoplasias, and/or malignant cancers in different
      organs. Women are more susceptible to the oncogenic effect of HPVs, mostly at the
      genital site on the uterine cervix. AIMS: This review analyzes the impact of: (i)
      genital warts (GWs) and their treatment; (ii) HPV-related genital, oral, and anal
      precancerous lesions on women's sexual function. METHODS: A Medline search was
      carried out. Search terms were HPV, GWs, intraepithelial neoplasia, cervical
      cancer, anal cancer, oral cancer, epidemiology, HPV risk factors, sexual
      dysfunctions, desire disorders, arousal disorders, dyspareunia, vulvar
      vestibulitis, vulvodynia, orgasmic difficulties, sexual repertoire, couple sexual
      problems, depression, anxiety, pap smear, screening program, therapy, and
      vaccines. MAIN OUTCOME MEASURES: Sexual consequences of HPV infection in women,
      specifically GWs and intraepithelial HPV-related neoplasia. RESULTS: Psychosexual
      vulnerability increases with number of recurrences of HPV infections. Depression,
      anxiety, and anger are the emotions most frequently reported. However, to date,
      there is no conclusive evidence of a specific correlation between HPV infection
      and a specific female sexual disorder. The relationship between HPV and vulvar
      vestibulitis/vulvodynia-related dyspareunia seems not to be direct. Counseling
      problems, the role of anti-HPV vaccine, and the concept of the high-risk partner
      are discussed. The reader is offered a practical approach with clinically
      relevant recommendations that may prove useful in his/her daily practice when
      dealing with HPV-infected women and couples. CONCLUSION: The evidence of
      psychosexual consequences of HPV-related GWs and intraepithelial lesions is
      limited. Specific research on the sexual impact of GWs and intraepithelial HPV
      related lesion in women is urgently needed.

PMID- 19170870
TI  - KOPS-guided DNA translocation by FtsK safeguards Escherichia coli chromosome
      segregation.
AB  - The septum-located DNA translocase, FtsK, acts to co-ordinate the late steps of
      Escherichia coli chromosome segregation with cell division. The FtsK gamma
      regulatory subdomain interacts with 8 bp KOPS DNA sequences, which are oriented
      from the replication origin to the terminus region (ter) in each arm of the
      chromosome. This interaction directs FtsK translocation towards ter where the
      final chromosome unlinking by decatenation and chromosome dimer resolution
      occurs. Chromosome dimer resolution requires FtsK translocation along DNA and its
      interaction with the XerCD recombinase bound to the recombination site, dif,
      located within ter. The frequency of chromosome dimer formation is approximately
      15% per generation in wild-type cells. Here we characterize FtsK alleles that no
      longer recognize KOPS, yet are proficient for translocation and chromosome dimer
      resolution. Non-directed FtsK translocation leads to a small reduction in fitness
      in otherwise normal cell populations, as a consequence of approximately 70% of
      chromosome dimers being resolved to monomers. More serious consequences arise
      when chromosome dimer formation is increased, or their resolution efficiency is
      impaired because of defects in chromosome organization and processing. For
      example, when Cre-loxP recombination replaces XerCD-dif recombination in dimer
      resolution, when functional MukBEF is absent, or when replication terminates away
      from ter.

PMID- 19170871
TI  - Ss-LrpB, a transcriptional regulator from Sulfolobus solfataricus, regulates a
      gene cluster with a pyruvate ferredoxin oxidoreductase-encoding operon and
      permease genes.
AB  - Ss-LrpB is an Lrp-like transcriptional regulator from Sulfolobus solfataricus.
      Previously, in vitro binding of Ss-LrpB to the control region of its own gene has
      been extensively studied. However, nothing was known about the physiological role
      of this regulator yet. Here, using the knowledge of the DNA-binding sequence
      specificity of Ss-LrpB, several potential binding sites were predicted in silico
      in promoter regions of genes located adjacently to the Ss-lrpB gene. These genes
      include an operon encoding a pyruvate ferredoxin oxidoreductase (porDAB) and two
      genes encoding putative permeases. In vitro protein-DNA interaction studies
      allowed the identification of the Ss-LrpB binding sites in the cognate control
      regions. Intriguingly, the binding site organization in the por operator is
      identical to that in the Ss-lrpB control region. An Ss-lrpB gene disruption
      mutant was constructed and the gene expression of the above-mentioned targets in
      this mutant was analysed by qRT-PCR and compared with isogenic wild type. Our
      data demonstrate that in vivo Ss-LrpB acts as an activator at the promoters of
      the three predicted targets. Based on these results, it appears that not all
      regulators belonging to the archaeal Lrp family perform a function related to the
      amino acid metabolism, unlike the bacterial Lrp-like regulators.

PMID- 19170872
TI  - Programmed drug-dependent ribosome stalling.
AB  - The ribosome has the intrinsic capacity to monitor the sequence and structure of
      the nascent peptide. This fundamental property of the ribosome is often exploited
      in regulation of gene expression, in particular, for activation of expression of
      genes conferring resistance to ribosome-targeting antibiotics. Induction of
      expression of these genes is controlled by the programmed stalling of the
      ribosome at a regulatory open reading frame located upstream of the resistance
      cistron. Formation of the stalled translation complex depends on the presence of
      an antibiotic in the ribosome exit tunnel and the sequence of the nascent
      peptide. In this review, we summarize our current understanding of the molecular
      mechanisms of drug- and nascent peptide-dependent ribosome stalling.

PMID- 19170873
TI  - A Candida albicans-specific region of the alpha-pheromone receptor plays a
      selective role in the white cell pheromone response.
AB  - Candida albicans strains homozygous at the mating type locus can switch from
      white to opaque, and must do so to mate. Opaque cells then secrete mating
      pheromones that stimulate opaque cells of opposite mating type to undergo mating.
      These same pheromones stimulate mating-incompetent white cells to become cohesive
      and adhesive, and enhance white cell biofilm development, a pathogenic trait.
      Stimulation is mediated through the same receptor, G protein complex and mitogen
      activated protein kinase pathway. Here we present evidence that a C. albicans
      specific 55-amino-acid region of the first intracellular loop, IC1, of the alpha
      pheromone receptor Ste2p, is required for the alpha-pheromone response of white
      cells, but not that of opaque cells. This represents a unique regulatory
      configuration in which activation of a common pathway by the same ligand, the
      same receptor and the same signal transduction pathway is dependent on a unique
      region of an intracellular loop of the common receptor in one of the two
      responding phenotypes.

PMID- 19170874
TI  - Leptosphaeria maculans avirulence gene AvrLm4-7 confers a dual recognition
      specificity by the Rlm4 and Rlm7 resistance genes of oilseed rape, and
      circumvents Rlm4-mediated recognition through a single amino acid change.
AB  - Leptosphaeria maculans is the ascomycete responsible for one of the most damaging
      diseases of oilseed rape (Brassica napus), stem canker of crucifers. Both
      avirulence (AvrLm) genes in the fungus and resistance (Rlm) genes in the plant
      are genetically clustered. Using a map-based cloning strategy, we delineated a
      238 kb region containing the AvrLm7 locus. Structural features of the region were
      reminiscent of those previously found on another chromosome for genomic regions
      encompassing AvrLm1 and AvrLm6, i.e. GC-equilibrated, gene-rich isochores
      alternating with AT-rich, recombination-deficient, gene-poor isochores. These
      latter corresponded to mosaics of degenerated and truncated transposable
      elements. AvrLm7 is the only gene located within a 60 kb AT-rich isochore. It
      induced resistance responses in plants harbouring either Rlm7 or Rlm4, and was
      thus renamed AvrLm4-7. It encodes a 143-amino-acid cysteine-rich protein,
      predicted to be secreted, and strongly induced during early stages of plant
      infection. Sequencing and restriction analyses of AvrLm4-AvrLm7 or avrLm4-AvrLm7
      alleles in L. maculans field isolates, and targeted point mutagenesis strongly
      suggested that one single base mutation, leading to the change of a glycine to an
      arginine residue, was responsible for the loss of AvrLm4 specificity whereas
      AvrLm7 recognition was unaltered.

PMID- 19170875
TI  - DnaA protein interacts with RNA polymerase and partially protects it from the
      effect of rifampicin.
AB  - The Escherichia coli DnaA protein forms an oligomer at the origin and initiates
      chromosome replication with the aid of architectural elements and transcription
      by RNA polymerase. Rifampicin inhibits initiation of transcription by RNA
      polymerase and thus also initiation of replication. Here, we report that wild
      type cells undergo rifampicin-resistant initiation of replication during slow
      growth in acetate medium. The rifampicin-resistant initiation was prevented by
      reducing the availability of DnaA. In vitro experiments showed that the DnaA
      protein interacted with RNA polymerase and that it afforded a partial protection
      from the negative effect of rifampicin. It is possible that rifampicin-resistant
      rounds of replication occur when a surplus of DnaA is available at the origin. In
      rich medium wild-type cells do not exhibit rifampicin-resistant rounds of
      replication, possibly indicating that there is no surplus DnaA, and that DnaA
      activity is the factor limiting the process of initiation. During growth in
      acetate medium, on the contrary, DnaA activity is not limiting in the same way
      because an initiation potential is present and can be turned into extra rounds of
      replication when rifampicin is added. The result suggests that regulation of
      replication initiation may differ at different growth rates.

PMID- 19170876
TI  - Production, characterization and determination of the real catalytic properties
      of the putative 'succinate dehydrogenase' from Wolinella succinogenes.
AB  - Both the genomes of the epsilonproteobacteria Wolinella succinogenes and
      Campylobacter jejuni contain operons (sdhABE) that encode for so far
      uncharacterized enzyme complexes annotated as 'non-classical' succinate:quinone
      reductases (SQRs). However, the role of such an enzyme ostensibly involved in
      aerobic respiration in an anaerobic organism such as W. succinogenes has hitherto
      been unknown. We have established the first genetic system for the manipulation
      and production of a member of the non-classical succinate:quinone oxidoreductase
      family. Biochemical characterization of the W. succinogenes enzyme reveals that
      the putative SQR is in fact a novel methylmenaquinol:fumarate reductase (MFR)
      with no detectable succinate oxidation activity, clearly indicative of its
      involvement in anaerobic metabolism. We demonstrate that the hydrophilic subunits
      of the MFR complex are, in contrast to all other previously characterized members
      of the superfamily, exported into the periplasm via the twin-arginine
      translocation (tat)-pathway. Furthermore we show that a single amino acid
      exchange (Ala86-->His) in the flavoprotein of that enzyme complex is the only
      additional requirement for the covalent binding of the otherwise non-covalently
      bound FAD. Our results provide an explanation for the previously published
      puzzling observation that the C. jejuni sdhABE operon is upregulated in an oxygen
      limited environment as compared with microaerophilic laboratory conditions.

PMID- 19170877
TI  - Amino acid 310 determines the donor substrate specificity of serogroup W-135 and
      Y capsule polymerases of Neisseria meningitidis.
AB  - The capsular polysaccharides of serogroup W-135 and Y meningococci are sialic
      acid-containing heteropolymers, with either galactose or glucose as the second
      sugar residue. As shown previously, sequences of the predicted enzymes that
      catalyse capsule polymerization, i.e. SiaD(W-135) and SiaD(Y), differ in only a
      few amino acids. By in vitro assays with purified recombinant proteins, SiaD(W
      135) and SiaD(Y) were now confirmed to be the capsule polymerases harbouring both
      hexosyltransferase and sialyltransferase activity. In order to identify amino
      acids crucial for substrate specificity of the capsule polymerases, polymorphic
      sites were narrowed down by DNA sequence comparisons and subsequent site-directed
      mutagenesis. Serogroup-specific amino acids were restricted to the N-terminal
      part of the proteins. Exclusively amino acid 310, located within the nucleotide
      recognition domain of the enzymes' predicted hexosyltransferase moiety, accounted
      for substrate specificity as shown by immunochemistry and in vitro activity
      assay. Pro-310 determined galactosyltransferase activity that resulted in a
      serogroup W-135 capsule and Gly-310 determined glucosyltransferase activity that
      resulted in a serogroup Y capsule. In silico analysis revealed a similar amino
      acid-based association in other members of the same glycosyltransferase family
      irrespective of the bacterial species.

PMID- 19170878
TI  - Parts exchange: tuning the flagellar motor to fit the conditions.
AB  - Many cellular activities are driven by complex protein machines. By measuring the
      behaviour of fluorescent protein fusions in real time in living cells it has
      become apparent that many of these complexes are not fixed, but are dynamic. To
      some extent this might be expected, for example, for cell division complexes, as
      defining mid-cell is linked to growth and cell cycle, but perhaps comes as more
      of a surprise with a complex anchored machine like the bacterial flagellar motor.
      The assumption has been that once made it remains intact. However, the dynamics
      of this structure is strongly supported in two manuscripts in this issue of
      Molecular Microbiology. The stator units which form a peptioglycan anchored ring
      around the rotor, generating torque in response to the ion motive force, clearly
      disengage when conditions change. The driving ion is shown to be important in
      both engagement of the stator to the rotor and the selection of the type of
      stator unit. These new results provide an insight into the mechanisms underlying
      motor function, which might rely on dynamic processes, and clearly illustrate the
      need to move away from a static view of cellular structures.

PMID- 19170879
TI  - Genome-wide responses to carbonyl electrophiles in Bacillus subtilis: control of
      the thiol-dependent formaldehyde dehydrogenase AdhA and cysteine proteinase YraA
      by the MerR-family regulator YraB (AdhR).
AB  - Quinones and alpha,beta-unsaturated carbonyls are naturally occurring
      electrophiles that target cysteine residues via thiol-(S)-alkylation. We analysed
      the global expression profile of Bacillus subtilis to the toxic carbonyls
      methylglyoxal (MG) and formaldehyde (FA). Both carbonyl compounds cause a stress
      response characteristic for thiol-reactive electrophiles as revealed by the
      induction of the Spx, CtsR, CymR, PerR, ArsR, CzrA, CsoR and SigmaD regulons. MG
      and FA triggered also a SOS response which indicates DNA damage. Protection
      against FA is mediated by both the hxlAB operon, encoding the ribulose
      monophosphate pathway for FA fixation, and a thiol-dependent formaldehyde
      dehydrogenase (AdhA) and DJ-1/PfpI-family cysteine proteinase (YraA). The adhA
      yraA operon and the yraC gene, encoding a gamma-carboxymuconolactone
      decarboxylase, are positively regulated by the MerR-family regulator, YraB(AdhR).
      AdhR binds specifically to its target promoters which contain a 7-4-7 inverted
      repeat (CTTAAAG-N4-CTTTAAG) between the -35 and -10 elements. Activation of adhA
      yraA transcription by AdhR requires the conserved Cys52 residue in vivo. We
      speculate that AdhR is redox-regulated via thiol-(S)-alkylation by aldehydes and
      that AdhA and YraA are specifically involved in reduction of aldehydes and
      degradation or repair of damaged thiol-containing proteins respectively.

PMID- 19170880
TI  - Physical-chemical plant-derived signals induce differentiation in Ustilago
      maydis.
AB  - Ustilago maydis is able to initiate pathogenic development after fusion of two
      haploid cells with different mating type. On the maize leaf surface, the
      resulting dikaryon switches to filamentous growth, differentiates appressoria and
      penetrates the host. Here, we report on the plant signals required for filament
      formation and appressorium development in U. maydis. In vitro, hydroxy-fatty
      acids stimulate filament formation via the induction of pheromone genes and this
      signal can be bypassed by genetically activating the downstream MAP kinase
      module. Hydrophobicity also induces filaments and these resemble the dikaryotic
      filaments formed on the plant surface. With the help of a marker gene that is
      specifically expressed in the tip cell of those hyphae that have formed an
      appressorium, hydrophobicity is shown to be essential for appressorium
      development in vitro. Hydroxy-fatty acids or a cutin monomer mixture isolated
      from maize leaves have a stimulatory role when a hydrophobic surface is provided.
      Our results suggest that the early phase of communication between U. maydis and
      its host plant is governed by two different stimuli.

PMID- 19170881
TI  - Two different stator systems drive a single polar flagellum in Shewanella
      oneidensis MR-1.
AB  - The Gram-negative metal ion-reducing bacterium Shewanella oneidensis MR-1 is
      motile by means of a single polar flagellum. We identified two potential stator
      systems, PomAB and MotAB, each individually sufficient as a force generator to
      drive flagellar rotation. Physiological studies indicate that PomAB is sodium
      dependent while MotAB is powered by the proton motive force. Flagellar function
      mainly depends on the PomAB stator; however, the presence of both stator systems
      under low-sodium conditions results in a faster swimming phenotype. Based on
      stator homology analysis we speculate that MotAB has been acquired by lateral
      gene transfer as a consequence of adaptation to a low-sodium environment.
      Expression analysis at the single cell level showed that both stator systems are
      expressed simultaneously. An active PomB-mCherry fusion protein effectively
      localized to the flagellated cell pole in 70-80% of the population independent of
      sodium concentrations. In contrast, polar localization of MotB-mCherry increased
      with decreasing sodium concentrations. In the absence of the Pom stator, MotB
      mCherry localized to the flagellated cell pole independently of the sodium
      concentration but was rapidly displaced upon expression of PomAB. We propose that
      selection of the stator occurs at the level of protein localization in response
      to sodium concentrations.

PMID- 19170882
TI  - Sequence requirements for the export of the Plasmodium falciparum Maurer's clefts
      protein REX2.
AB  - A short motif termed Plasmodium export element (PEXEL) or vacuolar targeting
      signal (VTS) characterizes Plasmodium proteins exported into the host cell. These
      proteins mediate host cell modifications essential for parasite survival and
      virulence. However, several PEXEL-negative exported proteins indicate that the
      currently predicted malaria exportome is not complete and it is unknown whether
      and how these proteins relate to PEXEL-positive export. Here we show that the N
      terminal 10 amino acids of the PEXEL-negative exported protein REX2 (ring
      exported protein 2) are necessary for its targeting and that a single-point
      mutation in this region abolishes export. Furthermore we show that the REX2
      transmembrane domain is also essential for export and that together with the N
      terminal region it is sufficient to promote export of another protein. An N
      terminal region and the transmembrane domain of the unrelated PEXEL-negative
      exported protein SBP1 (skeleton-binding protein 1) can functionally replace the
      corresponding regions in REX2, suggesting that these sequence features are also
      present in other PEXEL-negative exported proteins. Similar to PEXEL proteins we
      find that REX2 is processed, but in contrast, detect no evidence for N-terminal
      acetylation.

PMID- 19170883
TI  - Legionella pneumophila couples fatty acid flux to microbial differentiation and
      virulence.
AB  - During its life cycle, Legionella pneumophila alternates between at least two
      phenotypes: a resilient, infectious form equipped for transmission and a
      replicative cell type that grows in amoebae and macrophages. Considering its
      versatility, we postulated that multiple cues regulate L. pneumophila
      differentiation. Beginning with a Biolog Phenotype MicroArray screen, we
      demonstrate that excess short-chain fatty acids (SCFAs) trigger replicative cells
      to cease growth and activate their panel of transmissive traits. To co-ordinate
      their response to SCFAs, L. pneumophila utilizes the LetA/LetS two-component
      system, but not phosphotransacetylase or acetyl kinase, two enzymes that generate
      high-energy phosphate intermediates. Instead, the stringent response enzyme SpoT
      appears to monitor fatty acid biosynthesis to govern transmission trait
      expression, as an altered distribution of acylated acyl carrier proteins
      correlated with the SpoT-dependent differentiation of cells treated with either
      excess SCFAs or the fatty acid biosynthesis inhibitors cerulenin and 5
      (tetradecyloxy)-2-furoic acid. We postulate that, by exploiting the stringent
      response pathway to couple cellular differentiation to its metabolic state, L.
      pneumophila swiftly acclimates to stresses encountered in its host or the
      environment, thereby enhancing its overall fitness.

PMID- 19170884
TI  - Glycolipids are involved in biofilm accumulation and prolonged bacteraemia in
      Enterococcus faecalis.
AB  - Biofilm production is thought to be an important step in many enterococcal
      infections. In several Gram-positive bacteria, membrane glycolipids have been
      implicated in biofilm formation. We constructed a non-polar deletion mutant of a
      putative glucosyltransferase designated biofilm-associated glycolipid synthesis A
      (bgsA) in Enterococcus faecalis 12030. Analysis of major extracted glycolipids by
      nuclear magnetic resonance spectroscopy revealed that the cell membrane of 12030
      Delta bgsA was devoid of diglucosyl-diacylglycerol (DGlcDAG), while monoglucosyl
      diacylglycerol was overrepresented. The cell walls of 12030 Delta bgsA contained
      longer lipoteichoic acid molecules and were less hydrophobic than wild-type
      bacteria. Inactivation of bgsA in E. faecalis 12030 and E. faecalis V583 led to
      an almost complete arrest of biofilm formation on plastic surfaces.
      Overexpression of bgsA, on the other hand, resulted in increased biofilm
      production. While initial adherence was not affected, bgsA-deficient bacteria did
      not accumulate in the growing biofilm. Also, adherence of E. faecalis Delta bgsA
      to Caco-2 cells was impaired. In a mouse bacteraemia model, E. faecalis 12030
      Delta bgsA was cleared more rapidly from the bloodstream than the wild-type
      strain. In summary, BgsA is a glycosyltransferase synthetizing DGlcDAG, a
      glycolipid and lipoteichoic acid precursor involved in biofilm accumulation,
      adherence to host cells, and virulence in vivo.

PMID- 19170885
TI  - Holliday junction formation by the Borrelia burgdorferi telomere resolvase, ResT:
      implications for the origin of genome linearity.
AB  - Spirochetes of the genus Borrelia include the causative agents of Lyme disease
      and relapsing fever. They possess unusual, highly segmented genomes composed
      mostly of linear replicons with covalently closed hairpin telomeres. The
      telomeres are formed from inverted repeat replicated telomere junctions (rTels)
      by the telomere resolvase, ResT. ResT uses a reaction mechanism with similarities
      to that employed by the type IB topoisomerases and tyrosine recombinases. Here,
      we report that the relationship of ResT to the tyrosine recombinases extends to
      the ability to synapse-replicated telomeres and to catalyse the formation of a
      Holliday junction. We also report that ResT can use asymmetrized substrates that
      mimic the properties of a recombination site for a tyrosine recombinase, to form
      Holliday junctions. We propose a model for how this explains the origin of genome
      linearity in the genus Borrelia.

PMID- 19170887
TI  - The CHAP domain of Cse functions as an endopeptidase that acts at mature septa to
      promote Streptococcus thermophilus cell separation.
AB  - Cell separation is dependent on cell wall hydrolases that cleave the
      peptidoglycan shared between daughter cells. In Streptococcus thermophilus, this
      step is performed by the Cse protein whose depletion resulted in the formation of
      extremely long chains of cells. Cse, a natural chimeric enzyme created by domain
      shuffling, carries at least two important domains for its activity: the LysM
      expected to be responsible for the cell wall-binding and the CHAP domain
      predicted to contain the active centre. Accordingly, the localization of Cse on
      S. thermophilus cell surface has been undertaken by immunogold electron and
      immunofluorescence microscopies using of antibodies raised against the N-terminal
      end of this protein. Immunolocalization shows the presence of the Cse protein at
      mature septa. Moreover, the CHAP domain of Cse exhibits a cell wall lytic
      activity in zymograms performed with cell walls of Micrococcus lysodeikticus,
      Bacillus subtilis and S. thermophilus. Additionally, RP-HPLC analysis of
      muropeptides released from B. subtilis and S. thermophilus cell wall after
      digestion with the CHAP domain shows that Cse is an endopeptidase. Altogether,
      these results suggest that Cse is a cell wall hydrolase involved in daughter cell
      separation of S. thermophilus.

PMID- 19170886
TI  - Acid stress activation of the sigma(E) stress response in Salmonella enterica
      serovar Typhimurium.
AB  - The alternative sigma factor sigma(E) is activated by unfolded outer membrane
      proteins (OMPs) and plays an essential role in Salmonella pathogenesis. The
      canonical pathway of sigma(E) activation in response to envelope stress involves
      sequential proteolysis of the anti-sigma factor RseA by the PDZ proteases DegS
      and RseP. Here we show that sigma(E) in Salmonella enterica sv. Typhimurium can
      also be activated by acid stress. A sigma(E)-deficient mutant exhibits increased
      susceptibility to acid pH and reduced survival in an acidified phagosomal
      vacuole. Acid activation of sigma(E)-dependent gene expression is independent of
      the unfolded OMP signal or the DegS protease but requires processing of RseA by
      RseP. The RseP PDZ domain is indispensable for acid induction, suggesting that
      acid stress may disrupt an inhibitory interaction between RseA and the RseP PDZ
      domain to allow RseA proteolysis in the absence of antecedent action of DegS.
      These observations demonstrate a novel environmental stimulus and activation
      pathway for the sigma(E) regulon that appear to be critically important during
      Salmonella-host cell interactions.

PMID- 19170888
TI  - Vectorial transport and folding of an autotransporter virulence protein during
      outer membrane secretion.
AB  - Autotransporter (AT) proteins are a large and diverse family of extracellular
      virulence proteins from Gram-negative bacteria, characterized by a central beta
      helix domain within the mature virulence protein. It is not clear how these
      proteins cross the outer membrane (OM) quickly and efficiently, without
      assistance from an external energy source such as ATP or a proton gradient.
      Conflicting results in the literature have led to several proposed mechanisms for
      AT OM secretion, including a concerted process, or vectorial secretion with
      different directionalities. We introduced pairs of cysteine residues into the
      passenger sequence of pertactin, an AT virulence protein from Bordetella
      pertussis, and show that OM secretion of the passenger domain stalls due to the
      formation of a disulphide bond. We further show that the C-terminus of the
      pertactin passenger domain beta-helix crosses the OM first, followed by the N
      terminal portions of the virulence protein. In vivo proteolytic digestion shows
      that the C-terminus is exposed to the extracellular milieu during stalling, and
      forms stable structure. These AT secretion and folding features can potentially
      facilitate efficient secretion.

PMID- 19170890
TI  - Granzyme-b mediated cell death in the spinal cord-injured rat model.
AB  - Spinal cord injury initiates a complex series of inflammatory and immune
      responses including the influx of monocytes, macrophages, T-cells, NK cells and
      so on, into the injured area. In the present study, we found a significant
      increase in the levels of granzyme-b (gra-b) from the first day after the
      transection until the third day, with decrease in intensity thereafter. The
      chemokine IP-10/CXCL10 was also found to be elevated along with gra-b correlating
      with the infiltration of CD-8(+) cytotoxic T lymphocytes (CTLs) into the injured
      spinal cord. We observed an increase in the levels of the 64 kDa poly ADP ribose
      polymerase fragment, known to be a signature fragment produced by gra-b.
      Localization of gra-b in TUNEL positive neurons indicates that gra-b might play a
      crucial role in neuronal death and contributes to the pathophysiology of spinal
      cord injury.

PMID- 19170891
TI  - In vivo expression of proinflammatory cytokines in HIV encephalitis: an analysis
      of 11 autopsy cases.
AB  - As the pathogenesis of AIDS dementia complex (ADC), cytokines such as TNF-alpha
      and IL-1beta have been thought to have toxic effects on CNS cells and induce
      neuronal cell death. However, many of the discussions have been based on the
      studies done by in vitro experiments. There are only a few reports which
      demonstrate proinflammatory cytokines directly in vivo in HIV encephalitis (HIVE)
      brains, and roles of these cytokines with relation to HIV-1 infection are not yet
      clarified. In the present study, we examined 11 autopsy cases of HIVE using
      immunohistochemistry, and explored which cell types expressed these cytokines and
      whether expression of cytokines was related to viral infection. IL-1beta was
      detected in the frontal white matter of all 11 cases where microglial nodules
      were observed to varying degrees, whereas TNF-alpha was detected in seven cases.
      IL-1beta- or TNF-alpha-positive cells were almost restricted to CD68-positive
      macrophages/microglia and mild expression of these cytokines by astrocytes was
      observed in two cases with severe HIVE. IL-1beta was detected in some HIVp24
      positive multinucleated giant cells. However, we could not detect TNF-alpha
      expression in the HIVp24-positive cells, which indicates that IL-1beta is induced
      by HIV-1 infection. In conclusion, a macrophage/microglia lineage is the main
      cell type to release cytokines in HIVE, and IL-1beta expression by HIV-1-infected
      cells may be one of the important factors for induction of HIVE. In addition,
      many non-infected macrophages/microglia as well as some astrocytes express IL
      1beta and TNF-alpha, which might contribute to pathogenesis of ADC.

PMID- 19170889
TI  - Threonine phosphorylation prevents promoter DNA binding of the Group B
      Streptococcus response regulator CovR.
AB  - All living organisms communicate with the external environment for their survival
      and existence. In prokaryotes, communication is achieved by two-component systems
      (TCS) comprising histidine kinases and response regulators. In eukaryotes,
      signalling is accomplished by serine/threonine and tyrosine kinases. Although TCS
      and serine/threonine kinases coexist in prokaryotes, direct cross-talk between
      these families was first described in Group B Streptococcus (GBS). A
      serine/threonine kinase (Stk1) and a TCS (CovR/CovS) co-regulate toxin expression
      in GBS. Typically, promoter binding of regulators like CovR is controlled by
      phosphorylation of the conserved active site aspartate (D53). In this study, we
      show that Stk1 phosphorylates CovR at threonine 65. The functional consequence of
      threonine phosphorylation of CovR in GBS was evaluated using phosphomimetic and
      silencing substitutions. GBS encoding the phosphomimetic T65E allele are
      deficient for CovR regulation unlike strains encoding the non-phosphorylated T65A
      allele. Further, compared with wild-type or T65A CovR, the T65E CovR is unable to
      bind promoter DNA and is decreased for phosphorylation at D53, similar to Stk1
      phosphorylated CovR. Collectively, we provide evidence for a novel mechanism of
      response regulator control that enables GBS (and possibly other prokaryotes) to
      fine-tune gene expression for environmental adaptation.

PMID- 19170892
TI  - Pineal parenchymal tumor of intermediate differentiation showing malignant
      progression at relapse.
AB  - Pineal parenchymal tumors of intermediate differentiation (PPTID) are extremely
      rare tumor entities and only limited data are available regarding their
      pathologic features and biologic behavior. In this report, we describe a case of
      PPTID transformed into pineoblastoma at relapse in a 47-year-old woman, focusing
      on the comparison of histologic and immunohistochemical features between the
      first and recurred tumors. The first tumor in February 2004 exhibited diffuse
      sheets of relatively uniform, small cells with moderately high cellularity and
      mild nuclear atypia, and no mitoses or necrosis. Immunohistochemically, the tumor
      cells showed diffuse staining for neuron-specific enolase (NSE), synaptophysin
      and chromogranin, and the MIB-1 labeling index was 3%. The diagnosis was PPTID.
      On the other hand, 4 years later, the recurred tumor had morphologic features of
      undifferentiated small cell histology with high mitotic activity and prominent
      necrosis. Immunohistochemically, the tumor cells showed only focal, weak staining
      for NSE, synaptophysin and chromogranin, and the MIB-1 labeling index was 19%,
      all of which were the features of pineoblastoma. This case clearly indicates that
      PPTID can be transformed without limit into pineoblastoma at relapse in a
      clinical aspect, and PPTID is closely related to pineoblastoma on a continuous
      spectrum in a histogenetic aspect.

PMID- 19170893
TI  - Sporadic amyotrophic lateral sclerosis: Widespread multisystem degeneration with
      TDP-43 pathology in a patient after long-term survival on a respirator.
AB  - It has been reported that widespread multisystem degeneration can occur in
      patients with sporadic amyotrophic lateral sclerosis (SALS) who have survived for
      long periods with artificial respiratory support (ARS). We report a case of SALS
      of 8 years and 8 months duration in a 71-year-old woman, who received ARS for 7
      years and 8 months. In this patient, the symptoms at the early stage were those
      of typical ALS, and a totally locked-in state with frontal lobe atrophy appeared
      a few years after the start of ARS. At autopsy, marked atrophy of the frontal
      lobe and brainstem tegmentum was evident. Microscopically, widespread multisystem
      degeneration with obvious neuronal loss was a feature. Bunina bodies and
      ubiquitinated inclusions were observed in the remaining lower motor neurons. Of
      interest was that Lewy body-like hyaline inclusions (LBHIs), which were later
      shown to be immunnoreactive (ir) for 43-kDa TAR DNA-binding protein (TDP-43) and
      ubiquitin, were also detected in neurons in various regions of the nervous
      system, including the lower and upper motor neuron nuclei. The distributions of
      neurons with TDP-43-ir and ubiquitin-ir cytoplasmic inclusions were also
      widespread in the nervous system, and in each region, the numbers of these
      neurons were apparently larger than those of neurons with LBHIs. Importantly,
      double-labeling immunofluorescence revealed that the widespread TDP-43-ir
      inclusions were often ubiqutinated. In conclusion, the entire pathological
      picture appeared to correspond well to the patient's long-standing, progressive
      disease, including the TDP-43 pathology with ubiquitination. These findings
      further strengthen the idea that TDP-43 abnormality is closely associated with
      the pathogenesis of SALS.

PMID- 19170894
TI  - Methylation status of the MGMT gene promoter fails to predict the clinical
      outcome of glioblastoma patients treated with ACNU plus cisplatin.
AB  - We analyzed the methylation status of the O6-methylguanine-DNA methyltransferase
      (MGMT) promoter using a methylation-specific polymerase chain reaction (MSP) in
      glioblastoma patients treated with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2
      chloroethyl)-3-nitrosourea (ACNU) plus cisplatin followed by radiation therapy.
      Forty-eight patients with interpretable MSP results were included in this study.
      The MGMT promoter was methylated in 26 patients (54.2%, methylated group) and
      unmethylated in 22 patients (45.8%, unmethylated group). Comparison of clinical
      outcomes between the two groups revealed that the methylation status of the MGMT
      gene promoter was not a prognostic factor for overall survival (P = 0.516) or a
      predictive factor for radiological response to ACNU plus cisplatin treatment (P =
      0.529). The most noteworthy explanation for the result is that the synergistic
      antitumor effects of ACNU and cisplatin resulting from inactivation of MGMT by
      cisplatin in MGMT active tumors offset the drug resistance.

PMID- 19170895
TI  - Transplanted bone marrow stromal cells improves cognitive dysfunction due to
      diffuse axonal injury in rats.
AB  - Diffuse axonal injury (DAI) often leads to persistent cognitive dysfunction in
      spite of the lack of gross lesions on MRI. Therefore, this study was aimed to
      evaluate whether transplanted bone marrow stromal cells (BMSC) can improve DAI
      induced cognitive dysfunction or not. The rats were subjected to impact
      acceleration head injury, using a pneumatic high-velocity impactor. The BMSC were
      harvested from the mice and were cultured. The BMSC (4.0 x 10(5) cells) or
      vehicle were stereotactically transplanted into the right striatum at 10 days
      post-injury. Cognitive function analysis was repeated at 1, 2, and 4 weeks post
      injury, using the Morris water maze test. Histological analysis was performed at
      2, 8 and 20 weeks post-injury, using double fluorescence immunohistochemistry.
      Transplanted BMSC were widely distributed in the injured brain and gradually
      acquired the phenotypes of neurons and astrocytes over 20 weeks. In addition,
      they significantly improved DAI-induced cognitive dysfunction as early as 2 weeks
      post-injury, although their processes of neuronal differentiation were not
      completed at this time point. The findings suggest that the engrafted BMSC may
      exhibit this early beneficial effect on cognitive function by producing
      neuroprotective or neurotrophic factors. In conclusion, direct transplantation of
      BMSC may serve as a novel therapeutic strategy to enhance the recovery from DAI
      induced cognitive impairment.

PMID- 19170896
TI  - Transplanted human embryonic neural stem cells survive, migrate, differentiate
      and increase endogenous nestin expression in adult rat cortical peri-infarction
      zone.
AB  - Transplantation of stem cells is a potential therapeutic strategy for stroke
      damage. The survival, migration, and differentiation of transplanted human
      embryonic neural stem cells in the acute post-ischemic environment were
      characterized and endogenous nestin expression after transplantation was
      investigated. Human embryonic neural stem cells obtained from the temporal lobe
      cortex were cultured and labeled with fluorescent 1,1'-dioctadecy-6,6'-di (4
      sulfopheyl)-3,3,3',3'-tetramethylindocarbocyanin (DiI) in vitro. Labeled cells
      were transplanted into cortical peri-infarction zones of adult rats 24 h after
      permanent middle cerebral artery occlusion. Survival, migration, and
      differentiation of grafted cells were quantified in immunofluorescence-stained
      sections from rats sacrificed at 7, 14, and 28 days after transplantation.
      Endogenous nestin-positive cells in the cortical peri-infarction zone were
      counted at serial time points. The cells transplanted into the cortical peri
      infarction zone displayed the morphology of living cells and became widely
      located around the ischemic area. Moreover, some of the transplanted cells
      expressed nestin, GFAP, or NeuN in the peri-infarction zone. Furthermore,
      compared with the control group, endogenous nestin-positive cells in the peri
      infarction zone had increased significantly 7 days after cell transplantation.
      These results confirm the survival, migration, and differentiation of
      transplanted cells in the acute post-ischemic environment and enhanced endogenous
      nestin expression within a brief time window. These findings indicate that
      transplantation of neural stem cells into the peri-infarction zone may be
      performed as early as 24 h after ischemia.

PMID- 19170897
TI  - Clinicopathological study of early progressive multifocal leukoencephalopathy
      incidentally found in a schizophrenia patient.
AB  - A 58-year-old Japanese man developed psychomotor excitement and hallucinatory
      paranoia at age 53, which gradually developed to residual schizophrenia. He was
      administered various common tranquilizers until death. Myelodysplastic syndrome
      was noted 10 months before death. A routine autopsy was performed. The brain
      weighed 1365 g, and macroscopic observation revealed no remarkable findings.
      However, microscopic examination disclosed cells with enlarged and basophilic
      nuclei, and unusual astrocytes in the demyelinated foci, especially at the
      corticomedullary junctions in the temporal and occipital lobes. On the other
      hand, the white matter was relatively intact. Immunohistochemical analysis using
      anti-JC virus protein, VP-1 antibody, demonstrated JC virus-infected cells in not
      only abnormal glial cells and neurons but also normal-looking cells, which are
      suggestive of progressive multifocal leukoencephalopathy (PML). Immunostaining
      for GFAP revealed severe gliosis and some scattered abnormal enlarged nuclear
      cells in the lesions. Some clusters of CD8-positive lymphocytes were seen, which
      kill infected cells. PML could be considered a short-term disease preceding
      death, as "incidental PML" in this case. This is a rare autopsy case of early PML
      occurring in a schizophrenia patient with PML.

PMID- 19170898
TI  - Real-time PCR quantification and live-cell imaging of endophytic colonization of
      barley (Hordeum vulgare) roots by Fusarium equiseti and Pochonia chlamydosporia.
AB  - *New tools were developed for the study of the endophytic development of the
      fungal species Fusarium equiseti and Pochonia chlamydosporia in barley (Hordeum
      vulgare) roots. These were applied to monitor the host colonization patterns of
      these potential candidates for biocontrol of root pathogens. * Molecular beacons
      specific for either F. equiseti or P. chlamydosporia were designed and used in
      real-time polymerase chain reaction (PCR) quantification of fungal populations in
      roots. Genetic transformation of isolates with the green fluorescent protein
      (GFP) gene was carried out using an Agrobacterium tumefaciens-mediated
      transformation protocol, and spatial patterns of root colonization were
      investigated by laser confocal microscopy. * Quantification of endophytes by real
      time PCR in roots of barley gave similar results for all fungi, and was more
      accurate than culturing methods. Conversely, monitoring of root colonization by
      GFP-expressing transformants showed differences in the endophytic behaviours of
      the two species, and provided evidence of a plant response against endophyte
      colonization. * Both F. equiseti and P. chlamydosporia colonized barley roots
      endophytically, escaping attempts by the host to prevent fungal growth within
      root tissues. This strongly supports a balanced antagonism between the virulence
      of the colonizing endophyte and the plant defence response. Development of real
      time PCR techniques and GFP transformants of these fungal species will facilitate
      future work to determine their biocontrol capacity.

PMID- 19170899
TI  - Global patterns of ectomycorrhizal introductions.
AB  - Plants have often been moved across the globe with intact root systems. These
      roots are likely to have housed symbiotic ectomycorrhizal (EM) fungi and the
      movement of plants may have facilitated the introduction of EM fungi.Here, we
      report data compiled from a newly created database of EM fungal introductions.We
      estimate the magnitude of EM fungal introductions around the world and examine
      patterns associated with these introductions. We also use the data to develop a
      framework for understanding the invasion biology of EM fungi.At least 200 species
      of basidiomycete and ascomycete EM fungi have been moved from native ranges to
      novel habitats. The majority of recorded introductions are associated with Pinus
      or Eucalyptus plantations in the southern hemisphere. Most introduced species
      appear to be constrained from spreading in novel habitats and associate only with
      their introduced hosts. Aspects of life history, including host range, may
      influence the ability of EM species to establish or invade. Human-caused
      introductions of EM fungi are a common and global phenomenon.The mechanisms
      controlling EM fungi in novel habitats and potential impacts of EM fungal
      introductions are almost entirely unknown.

PMID- 19170900
TI  - Evidence for alteration of fungal endophyte community assembly by host defense
      compounds.
AB  - * Plant defense compounds are common stressors encountered by endophytes. Fungi
      readily evolve tolerance to these compounds, yet few studies have addressed the
      influence of intraspecific variation in defense compound production on endophyte
      colonization. We compared the influence of defense compound production on the
      composition of fungal endophyte communities in replicated field experiments. *
      Maize (Zea mays) produces benzoxazinoids (BXs), compounds with antifungal
      byproducts persistent in the environment. Fungi were isolated from leaf and root
      tissue of two maize genotypes that produce BXs, and a natural mutant that does
      not. Isolates representing the species recovered were tested for tolerance to 2
      benzoxazolinone (BOA), a toxic BX byproduct. * In seedling roots and mature
      leaves, the community proportion with low BOA tolerance was significantly greater
      in BX nonproducers than producers. Mean isolation frequency of Fusarium species
      was up to 35 times higher in mature leaves of BX producers than nonproducers. *
      Fungal species with relatively high tolerance to BOA are more abundant in BX
      producing than BX nonproducing maize. Production of BXs may increase colonization
      by Fusarium species in maize, including agents of animal toxicosis and yield
      reducing disease in maize. Overall, results indicate that production of defense
      compounds can significantly alter endophyte community assembly.

PMID- 19170901
TI  - Making sense of the new ICD algorithms for the treatment of fast ventricular
      tachycardia.

PMID- 19170902
TI  - Does ICD indication affect quality of life and levels of distress?
AB  - The implantable cardioverter defibrillator (ICD) is the treatment of choice for
      life-threatening arrhythmias, with ICD indications having recently been extended
      to include primary prophylaxis. Despite the medical benefits of the ICD, there is
      an ongoing debate as to the impact of the ICD on patients' lives, particularly
      whether primary prophylaxis implantation may impact adversely on patient-centered
      outcomes such as quality of life (QoL) and distress. We examined the evidence for
      a role of ICD indication on these patient-centered outcomes. A literature search
      was conducted on PubMed and Web of Science from 2002 to present, focusing on
      indication for ICD therapy and patient-centered outcomes (i.e., anxiety,
      depression, disease-specific, or general QoL). We identified five studies (seven
      articles) concerning the impact of indication on patient-centered outcomes.
      Sample sizes varied from 91-426 patients across studies, five of seven articles
      used a prospective design, and follow-up ranged from 2-12 months. No study
      reported an effect for indication on patient-centered outcomes. There is no
      evidence to suggest that patients receiving an ICD for primary prophylaxis have
      subsequent poorer QoL and greater distress than patients receiving an ICD for
      secondary prophylaxis. This knowledge may help cardiologists in the clinical
      management of patients, in particular when discussing ICD implantation with
      patients.

PMID- 19170903
TI  - Performance of dedicated versus integrated bipolar defibrillator leads with CRT
      defibrillators: results from a Prospective Multicenter Study.
AB  - INTRODUCTION: Right ventricular (RV) anodal stimulation may occur in cardiac
      resynchronization therapy defibrillators (CRT-D) when left ventricular (LV)
      pacing is configured between the LV lead and an electrode on the RV defibrillator
      lead. RV defibrillator leads can have a dedicated proximal pacing ring electrode
      (dedicated bipolar) or utilize the distal shocking coil as the proximal pacing
      electrode (integrated bipolar). This study compares the performance of integrated
      versus dedicated leads with respect to anodal stimulation incidence, sensing, and
      inappropriate ventricular tachyarrhythmia detection in patients implanted with
      CRT-D. METHODS: Two hundred ninety-two patients were randomly assigned to receive
      dedicated or integrated bipolar RV leads at the time of CRT-D implantation.
      Patients were followed for 6 months. RESULTS: Patients with dedicated bipolar RV
      leads exhibited markedly higher rates of anodal stimulation than did patients
      with integrated leads. The incidence of anodal stimulation was 64% at implant for
      dedicated bipolar RV leads compared to 1% for integrated bipolar RV leads. The
      likelihood of anodal stimulation in patients with dedicated leads fell
      progressively during the 6-month follow-up (51.5%), but always exceeded the
      incidence of anodal stimulation in patients with integrated leads (5%).
      Clinically detectable undersensing and oversensing were very unusual and did not
      differ significantly between lead designs. There were no inappropriate
      ventricular tachyarrhythmia detections for either lead type. CONCLUSION:
      Integrated bipolar RV defibrillator leads had a significantly lower incidence of
      RV anodal stimulation when compared to dedicated bipolar RV defibrillation leads,
      with no clinically detectable oversensing or undersensing, and with no
      inappropriate ventricular tachyarrhythmia detections for either lead type.

PMID- 19170904
TI  - A prospective randomized trial of defibrillation thresholds from the right
      ventricular outflow tract and the right ventricular apex.
AB  - BACKGROUND: Right ventricular outflow tract (RVOT) pacing has been suggested to
      improve hemodynamics and to help prevent pacing-induced cardiomyopathy. Pacing
      from the RVOT is feasible and equivalent in terms of sensing and stimulation
      threshold. However, physicians have been reluctant to use RVOT pacing because of
      concerns that defibrillation efficacy might be adversely affected. To date, there
      have been no randomized-controlled trials published comparing the defibrillation
      threshold in leads implanted in the RVOT and the right ventricular apex (RVA).
      OBJECTIVE: The purpose of this study was to compare defibrillation thresholds
      (DFT) in the RVOT and RVA. Ventricular sensing and stimulation thresholds were
      also compared. METHODS: This prospective, randomized, multicenter study included
      87 patients (70 males, age 69 +/- 11 years). At implantation, the patient's
      ventricular implantable cardioverter-defibrillator (ICD) lead position was
      randomized to either the RVOT or RVA. A four-shock Bayesian up-down method was
      used to determine the DFT. Patients were followed for 3 months postimplant.
      RESULTS: DFTs were not significantly different in leads implanted in the RVOT
      (median 8.8 J [6.28, 12.9] vs. 7.9 J [6.20, 12.6], P = 0.65). Threshold and
      impedance measurements were stable in both RVOT and RVA groups from implant to
      follow-up. All ICD leads remained stable chronically at the 3-month follow-up.
      CONCLUSION: DFTs in leads placed in the RVOT and RVA are comparable. RVOT ICD
      lead placement is safe and exhibits similar lead stability, threshold, and
      impedance measurements as the traditional RVA location.

PMID- 19170905
TI  - Right ventricular outflow tract septal pacing: long-term follow-up of ventricular
      lead performance.
AB  - BACKGROUND: The detrimental effects of right ventricular apical pacing on left
      ventricular function has driven interest in selective site pacing, predominantly
      on the right ventricular outflow tract (RVOT) septum. There is currently no
      information on long-term ventricular lead electrical performance from this site.
      METHODS: A total of 100 patients with ventricular lead placement on the RVOT
      septum undergoing pacemaker implantation for bradycardia indications were
      analyzed retrospectively. Lead positioning was confirmed with the use of
      fluoroscopy. Long-term (1 year) follow-up was obtained in 92 patients.
      Information on stimulation threshold, R-wave sensing, lead impedance, and lead
      complications were collected. RESULTS: Lead performance at the RVOT septal
      position was stable in the long term. Ventricular electrical parameters were
      acceptable with stable long-term stimulation thresholds, sensing, and impedance
      for all lead types. One-year results demonstrated mean stimulation threshold of
      0.71 +/- 0.25 V, mean R wave of 12.4 +/- 6.05 mV, and mean impedance values of
      520 +/- 127 Omega. There were no cases of high pacing thresholds or inadequate
      sensing. CONCLUSIONS: This study confirms satisfactory long-term performance with
      leads placed on the RVOT septum, comparable to traditional pacing sites. It is
      now time to undertake studies to examine the long-term hemodynamic effects of
      RVOT septal pacing.

PMID- 19170906
TI  - Leadless pacing of the heart using induction technology: a feasibility study.
AB  - OBJECTIVES: To develop a leadless pacemaker system based on induction technology
      and to investigate its feasibility and safety in the pig model. BACKGROUND:
      Despite tremendous technical advances during the last decades, cardiac pacing is
      still associated with a considerable rate of complications that can be primarily
      attributed to the leads. METHODS: The device consists of a transmitter unit
      implanted subcutaneously just above the heart and an endocardial receiver unit
      implanted in the apex of the right ventricle. The transmitter unit generates an
      alternating magnetic field that is converted into a voltage pulse by the receiver
      unit. In order to test feasibility, the receiver unit was attached to an
      electrophysiology catheter for signal recording and placed in the apex of the
      right ventricle of a pig. Subsequently, the receiver unit was implanted without
      external connection in the right ventricle. RESULTS: An alternating magnetic
      field of about 0.5 mT was generated by the transmitter unit in a distance of 3
      cm. Voltage pulses with a duration of 0.4 ms and voltage amplitude of 0.6-1.0 V
      were generated. Using these pulse characteristics, a reliable stimulation of the
      heart could be achieved. A secure fixation of the receiver unit in the apex of
      the right ventricle could be obtained for the duration of this short-term study
      by using screw fixation. CONCLUSIONS: This study shows that induction technology
      is feasible for cardiac pacing. Typical voltage pulses could be generated by
      which an effectively stimulation in vivo could be achieved.

PMID- 19170907
TI  - Increased anxiety in partners of patients with a cardioverter-defibrillator: the
      role of indication for ICD therapy, shocks, and personality.
AB  - BACKGROUND: The partner of the implantable cardioverter-defibrillator (ICD)
      patient serves as an important source of support for the patient, which may be
      hampered if the partner experiences increased distress. We examined (1) potential
      differences in anxiety and depressive symptoms in ICD patients compared to their
      partners, and (2) the extent to which the partner's personality is a more
      important determinant of partner distress than patient clinical characteristics,
      using a prospective design. METHODS: Consecutively implanted ICD patients (n =
      196) and their partners (n = 196) completed a set of psychological questionnaires
      at baseline and 6 months after implantation. RESULTS: Analysis of variance with
      repeated measures showed that partners had significantly higher levels of anxiety
      compared to patients (F(1,390) = 16.431; P < 0.001) but not depressive symptoms
      (F(1,390) = 0.186; P = 0.67). There was a significant overall reduction in
      anxiety (F(1,390) = 79.552; P < 0.001) and depressive symptoms (F(1,390) =
      39.868; P < 0.001) over 6 months, with group (i.e., patient vs partner) exerting
      a stable effect on anxiety (F(1,390) = 0.966; P = 0.33) and depressive symptoms
      (F(1,390) = 0.025; P = 0.87). These results remained in adjusted analysis.
      Determinants of anxiety and depressive symptoms in partners included secondary
      prophylaxis in patients (Ps < 0.001-0.002), Type D personality of the partner (Ps
      < 0.001-0.001), secondary prophylaxis by shock interaction (P = 0.002; anxiety
      only), and secondary prophylaxis by Type D interaction (Ps = 0.001-0.003).
      CONCLUSIONS: Partners had higher levels of anxiety but not depression than ICD
      patients. Partner distress could be attributed not only to the partner's
      personality, but also to patient clinical characteristics, primarily secondary
      prophylaxis for ICD therapy. These results indicate that information on the
      clinical characteristics of the patient in addition to partner characteristics
      may help identify partners at risk of distress.

PMID- 19170908
TI  - Radiofrequency catheter ablation of atrial flutter induces the release of
      platelet and leukocyte-derived procoagulant microparticles and a prothrombotic
      state.
AB  - BACKGROUND: To assess the extent of endothelium, platelet, and leukocyte damage
      and coagulation activation induced by radiofrequency catheter ablation (RF) of
      atrial flutter. In the vasculature, procoagulant microparticles (MPs) are
      reliable markers of vascular damage. They provide an additional phospholipidic
      surface, enabling the assembly of the enzyme complexes of blood coagulation and
      consequent thrombin generation. METHODS: MPs were measured in the venous blood of
      33 patients with isthmus-dependent atrial flutter undergoing RF before (RF(0)),
      immediately after (RF(1)), and at day 1 (RF(2)) thereafter. Concentrations of PAI
      1, vWF, and D-dimers were simultaneously determined. MPs procoagulant activities
      were determined using a functional prothrombinase assay. RF induces an early rise
      of platelet-derived MPs (platelet), vWF Ag, and D-dimers levels, which is
      concomitant with the decrease of PAI-1 concentrations. Conversely, no significant
      changes in endothelial-derived MPs could be evidenced. At RF(2), sustained
      elevation of leukocytes-derived MPs, vWF, and D-dimers testified to an ongoing
      prothrombotic status. CONCLUSION: RF ablation of common flutter induces a
      prothrombotic state and the release of platelet and leukocyte-derived
      procoagulant microparticles. Whereas this activation of blood coagulation could
      be viewed as clinically marginal in right-sided procedures, its relevance in left
      sided procedures should be established.

PMID- 19170909
TI  - Determinants of lesion dimensions during transcatheter microwave ablation.
AB  - BACKGROUND: Transcatheter microwave ablation is a novel technique for treating
      cardiac arrhythmias. METHODS: We investigated the effects of catheter
      temperature, application duration, and antenna length on lesion dimensions during
      catheter-based microwave ablation. In a swine thigh muscle preparation, microwave
      was delivered at targeted temperatures of 60 degrees C (n = 18), 70 degrees C (n
      = 27), 80 degrees C (n = 43), or 90 degrees C (n = 18) for 120 seconds with 10-mm
      antenna; and at targeted temperatures of 80 degrees C for 120 seconds (n = 22),
      150 seconds (n = 18), 180 seconds (n = 18), 210 seconds (n = 18), and 240 seconds
      (n = 17) with 20-mm antenna using 10 F catheter (MedWaves, San Diego, CA, USA)
      during parallel orientation. Conventional radiofrequency ablation (RF) using a 4
      mm tip electrode was performed as control. RESULTS: With 120-second energy
      applications, lesion length and depth were significantly larger with targeted
      temperatures of 80 degrees C and 90 degrees C than 60 degrees C (P< 0.05).
      Furthermore, lesion depth and width, but not length, were significantly increased
      by prolonging energy application duration from 120 to 240 seconds at targeted
      temperature of 80 degrees C (P< 0.05). Compared to RF, microwave lesions were
      significantly longer but had comparable depth and width. A 20-mm microwave
      antenna produced longer lesions than either a 10-mm antenna or RF ablation
      catheter. Multivariate analysis demonstrated that targeted temperature >or=80
      degrees C, application duration >or=150 seconds, and use of 20-mm antenna were
      independent predictors for lesion depth and width (P< 0.05). Surface dessication
      was observed in 4/18 (22%) lesions at 90 degrees C, as compared with 1/136 (0.7%)
      at 80 degrees C targeted tip temperature (P < 0.05). CONCLUSIONS: This study
      demonstrated that lesions size with transcatheter microwave ablation can be
      controlled by adjusting targeted temperature, energy application duration, and
      antenna length. A targeted temperature of 80 degrees C for more than 150 seconds
      should provide optimal lesion dimensions and lower risk of surface dessication or
      charring.

PMID- 19170910
TI  - New or aggravated heart failure during long-term right ventricular pacing after
      AV junctional catheter ablation.
AB  - BACKGROUND: Atrioventricular junctional ablation (AVJA) improves symptoms and
      quality of life in patients with pharmacologically resistant atrial fibrillation
      (AF). However, long-term right ventricular stimulation has also been reported to
      lead to deterioration of the left ventricular function. We retrospectively
      analyzed the incidence of new or aggravated heart failure (HF) during long-term
      right ventricular stimulation following AVJA. METHODS: Two hundred thirteen
      patients (110F:103M), 73 +/- 10 years old, were followed for a period of 6 +/- 3
      years after AVJA. Forty-nine patients (23%) were known to have HF before AVJA.
      New HF was diagnosed if at least two of the following criteria were present: NYHA
      class >2, an LVEF <45%, and medication for HF. Aggravated HF was defined as an
      increase in the functional class and/or new prescription of medication for HF.
      All-cause death was a secondary endpoint. RESULTS: During follow-up, 26% of the
      patients with known HF showed an aggravation of HF, while 13% developed new
      symptoms of HF. High age and low EF were independent predictors of new or
      aggravated HF and of new HF, while none of the tested variables predicted
      aggravation of known HF. The all-cause mortality was 16%, where high age and
      coronary artery disease were found to be independent predictors. CONCLUSION: AVJA
      followed by right ventricular pacing was associated with aggravated HF in 23% of
      patients with known HF, while development of new symptoms of HF occurred much
      less often during follow-up (13%). The majority of patients who underwent AVJA
      continued to do well during long-term follow-up.

PMID- 19170911
TI  - Reversal of atrial remodeling after cardioversion of persistent atrial
      fibrillation measured with magnetocardiography.
AB  - BACKGROUND: Atrial fibrillation (AF) causes electrical, functional, and
      structural changes in the atria. We examined electrophysiologic remodeling caused
      by AF and its reversal noninvasively by applying a new atrial signal analysis
      based on magnetocardiography (MCG). METHODS: In 26 patients with persistent AF,
      MCG, signal-averaged electrocardiography (SAECG), and echocardiography were
      performed immediately after electrical cardioversion (CV), and repeated after 1
      month in 15 patients who remained in sinus rhythm (SR). Twenty-four matched
      subjects without history of AF served as controls. P-wave duration (Pd) and
      dispersion (standard deviation of Pd values in individual channels) and root mean
      square amplitudes of the P wave over the last 40 ms portions (RMS40) were
      determined. RESULTS: In MCG Pd was longer (122.8 +/- 18.2 ms vs 101.5 +/- 14.6
      ms, P < 0.01) and RMS40 was higher (60.4 +/- 28.2 vs 46.9 +/- 19.1 fT) in AF
      patients immediately after CV as compared to the controls. In SAECG Pd dispersion
      was increased in AF patients. Mitral A-wave velocity and left atrial (LA)
      contraction were decreased and LA diameter was increased (all P < 0.01). After 1
      month, Pd in MCG still remained longer and LA diameter greater (both P < 0.05),
      while RMS40 in MCG, Pd dispersion in SAECG, mitral A-wave velocity, and LA
      contraction were recovered. CONCLUSIONS: Magnetocardiographically detected atrial
      electrophysiologic alterations in persistent AF diminish rapidly although
      incompletely during maintained SR after CV. This might be related to the known
      early high and late lower, but still existent tendency to AF relapses.

PMID- 19170912
TI  - Insights into the effects of contraction dyssynchrony on global left ventricular
      mechano-energetic function.
AB  - BACKGROUND: The effects of dyssynchrony on global left ventricular (LV) mechanics
      have been well documented; however, its impact on LV energetics has received less
      attention. OBJECTIVE: To assess the effects of LV contraction dyssynchrony on
      global LV mechano-energetic function in a pacing-induced acute model of
      dyssynchrony. METHODS: Using blood-perfused isolated rabbit heart preparations (n
      = 11), LV pressure, coronary flow, and arteriovenous oxygen content difference
      were recorded for isovolumic contractions under right atrial (RA) pacing
      (control) and simultaneous RA and right ventricular outflow tract (RVOT) pacing
      (dyssynchrony). LV mechanical function was quantified by the end-systolic
      pressure-volume relationship (ESPVR). Myocardial oxygen consumption-pressure
      volume area (MVO(2)-PVA) relationship quantified LV energetic function. Internal
      PVA for MVO(2 RVOT) was calculated based on the MVO(2)-PVA relationship for RA
      pacing. Thus, lost PVA (internal PVA-PVA(RVOT)) represents the mechanical energy
      not observable at the global level. RESULTS: Compared to RA pacing, RVOT pacing
      depressed LV mechanics as indicated by a rightward shift of ESPVR (i.e., increase
      in V(d) from 0.58 +/- 0.10 to 0.67 +/- 0.10 mL, P < 0.05). Despite depressed
      mechanics, RVOT pacing was associated with greater MVO(2) such that the MVO(2)
      PVA relationship intercept was markedly increased from 0.025 +/- 0.003 to 0.029
      +/- 0.003 mL*O(2)/beat/100gLV (P < 0.05). Excess MVO(2) (i.e., MVO(2 RVOT)- MVO(2
      RA)) significantly correlated with lost PVA (R(2)= 0.54, P < 0.001). CONCLUSION:
      A potential mechanism explaining the observed increase in MVO(2) with
      dyssynchrony may be that the measured PVA at the global level underestimates the
      internal PVA at the cellular level, which is likely to be the true determinant of
      MVO(2).

PMID- 19170913
TI  - Outcomes in adolescents with postural orthostatic tachycardia syndrome treated
      with midodrine and beta-blockers.
AB  - BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is associated with
      debilitating fatigue, dizziness, and discomfort in previously healthy
      adolescents. The effects of medical therapy have not been well studied in this
      patient population. This study assessed the relative efficacy and impact of drug
      therapy on the functioning and quality of life in adolescents with POTS. METHODS:
      A retrospective, single center, chart review analysis with a follow-up written
      survey was conducted on a group of 121 adolescents who had undergone autonomic
      reflex screening at the Mayo Clinic from 2002 to 2005 as part of an evaluation
      for possible POTS. RESULTS: Of 121 surveys sent, 47 adolescents returned a
      completed survey. In this cohort of patients, the two most commonly prescribed
      drug therapies were midodrine (n = 13) and beta-blockers (n = 14). Patients in
      the midodrine group were comparable to patients in the beta-blocker group in
      gender, age, pretreatment postural heart rate changes, and months from initial
      evaluation to survey completion. More patients treated with a beta-blocker
      reported improvement after visiting Mayo Clinic (100% vs 62%, P = 0.016) and more
      attributed their progress to medication (63.6% vs 36.4%, P = 0.011) than did
      those treated with midodrine. CONCLUSION: Treatment with both midodrine and beta
      blockers was associated with overall improvement in POTS patients' general
      health; however, adolescents taking beta-blockers were more likely than those
      taking midodrine to credit the role of medications in their improvement.

PMID- 19170914
TI  - The effects of trimetazidine on p-wave duration and dispersion in heart failure
      patients.
AB  - BACKGROUND: P-wave duration and dispersion (PWD) have been shown to be
      noninvasive predictors for development of atrial fibrillation. Thus, it may be
      possible to attenuate atrial fibrillation risk through normalization of P-wave
      duration and dispersion. Trimetazidine, a metabolic modulator, has been reported
      to improve cardiac function in heart failure (HF) patients. METHODS: Thirty-six
      HF patients being treated with angiotensin inhibitors, carvedilol,
      spironolactone, and furosemide were prescribed trimetazidine, 20 mg three times a
      day. Electrocardiographic and echocardiographic examinations were obtained before
      and 6 months after addition of trimetazidine in HF patients and 36 healthy
      control group patients having normal echocardiographic examination. RESULTS:
      Maximum P-wave duration (Pmax) (106.7 +/- 15.8 vs. 91.7 +/- 12.7 ms) and PWD
      (57.2 +/- 15.4 vs. 37.9 +/- 16.7 ms) were significantly longer in HF patients
      compared to the control group. There were significant correlations of Pmax and
      PWD with left atrial diameter (r = 0.508, P = < 0.001 and r = 0.315, P = 0.029),
      left ventricular ejection fraction (LVEF) (r = 0.401, p = 0.005 and r = 0.396, P
      = 0.005), deceleration time (r = 0.296, P = 0.032 and r = 0.312, P = 0.035), and
      isovolumetric relaxation time (r = 0.265, P = 0.038 and r = 0.322, P = 0.015).
      There were significant improvements in LVEF (32.7 +/- 6.5% to 37.2 +/- 5.5%, P =
      0.036), left atrial diameter (41.5 +/- 6.7 to 40.3 +/- 6.1 mm, P < 0.001), and
      Pmax (106.7 +/- 15.8 to 102.2 +/- 11.5 ms, P = 0.006) and PWD (57.2 +/- 15.4 to
      48.9 +/- 10.1 ms, P < 0.001) during follow-up. CONCLUSIONS: Trimetazidine added
      to optimal medical therapy in HF may improve Pmax and PWD in association with
      improved left ventricular function. Longer-term and larger studies are necessary
      to evaluate whether these findings may have clinical implications on prevention
      of atrial fibrillation.

PMID- 19170915
TI  - V-sense episode in a biventricular pacemaker device: what is the likely
      mechanism?

PMID- 19170916
TI  - Strategies to minimize the risk of esophageal injury during catheter ablation for
      atrial fibrillation.
AB  - Esophageal injury is a rare but serious complication of catheter ablation for
      atrial fibrillation using radiofrequency energy. Recent studies have begun to
      identify variables that may determine heat transfer to and thermal injury of the
      esophagus. There is significant variability in the relationship between the
      esophagus and left atrium among individuals. New imaging techniques can
      facilitate assessment of esophagus position relative to intended ablation
      targets. Strategies to minimize the risk of esophageal injury include avoidance
      of ablation near the esophagus, titration of RF energy delivery at the posterior
      left atrial endocardium, and the use of alternative ablation methods.

PMID- 19170917
TI  - The stirrup cup.

PMID- 19170918
TI  - Right atrial pacemaker lead thrombosis causing tricuspid inflow obstruction.
AB  - A 75-year-old man was admitted to our hospital with a complaint of progressive
      dyspnea with effort. The patient had a permanent pacemaker that was implanted 16
      years ago. Transesophageal echocardiography revealed a large, mobile mass in the
      right atrium attaching to the insertion site of the atrial lead at the tricuspid
      valve level. Because of the size, mobility, and location of the mass, urgent
      surgical removal was considered. The mass was successfully removed. Histologic
      examination of the mass demonstrated a partially organized thrombus. The
      postoperative course was uneventful and the patient's symptoms improved
      remarkably after operation.

PMID- 19170919
TI  - Coexisting idiopathic left ventricular tachycardia and atrioventricular reentrant
      tachycardia in a patient with wolff-Parkinson-white syndrome.
AB  - We report a patient with Wolff-Parkinson-White syndrome who presented with two
      distinct tachycardias that represented atrioventricular reentrant tachycardia
      utilizing left lateral accessory pathway (AP) and idiopathic left ventricular
      tachycardia (ILVT). Two tachycardias with a complete separate mechanism occurred
      spontaneously as well as following atrial or ventricular pacing. Successful
      ablation of the left AP and ILVT resulted in a cure of the double tachycardia.

PMID- 19170920
TI  - The characteristics of an abnormal electrogram on the atrialized right ventricle
      in a patient with Ebstein's anomaly.
AB  - Catheter ablation with the use of radiofrequency energy has been used as a
      treatment for atrioventricular reciprocating tachycardia in patients with
      Ebstein's anomaly. However, the success rate in these patients is generally low.
      We experienced a case in which the decision regarding precise accessory pathway
      (AP) localization was impaired by the presence of an abnormal electrogram in the
      atrialized right ventricle (ARV) in a patient with Ebstein's anomaly. After the
      AP conduction was abolished, the abnormal electrogram was observed behind the
      ventricular wave in the ARV during sinus rhythm. Furthermore, the interval
      between ventricular potential and the abnormal electrogram observed in the
      proximal ARV was longer than that in the distal ARV. We suggest that the abnormal
      electrogram might represent delayed local ventricular activation, and that the
      potential conduction might be impaired in the ARV.

PMID- 19170921
TI  - Left atrial substrate ablation in addition to pulmonary vein isolation in
      paroxysmal atrial fibrillation using a large 28-mm cryoballoon.
AB  - We report a case of successful isolation of all pulmonary veins (PV) for
      symptomatic paroxysmal atrial fibrillation using a 23-mm cryoballoon with
      continued paroxysmal atrial fibrillation during a 3-month follow-up. Left atrial
      to-PV-junction ablation was then performed 3 months after the first procedure
      using a larger 28-mm balloon despite unrecovered isolation of all four PV,
      thereby curing symptomatic atrial fibrillation in this case.

PMID- 19170922
TI  - Mapping and ablation of multiple atrial arrhythmias in a patient with persistent
      atrial standstill after remote viral myocarditis.
AB  - This is a case of multiple atrial arrhythmias (atrioventricular node reentry and
      two different focal atrial tachycardias) originating from the remaining atrial
      myocardium after global scarring of both atria following a remote viral
      myocarditis. All the induced arrhythmias were successfully treated with catheter
      ablation.

PMID- 19170923
TI  - Profound hypotension due to slow atrioventricular nodal pathway conduction during
      atrial tachycardia.
AB  - Paroxysmal supraventricular tachycardia (SVT) may have a variety of hemodynamic
      effects depending on rate, patient volume status, and presence of structural
      heart disease or left bundle branch block. We report a case of a patient with
      atrial tachycardia and dual atrioventricular (AV) nodal physiology who developed
      profound hypotension during transition from fast to slow AV nodal pathway
      conduction, despite similar tachycardia cycle length. This case illustrates the
      potential importance of AV timing in determining the hemodynamic effect of SVT.

PMID- 19170924
TI  - Use of coronary venous angioplasty to facilitate optimal placement of left
      ventricular lead during CRT.
AB  - Cardiac resynchronization therapy (CRT) has become an accepted treatment for
      selected patients with drug-resistant heart failure. In some cases CRT
      implantation can be difficult, particularly optimal left ventricular stimulation
      through proper lead placement. Difficulties can arise from venous stenosis,
      atypical and tortuous coronary sinus anatomy, presence of venous valves,
      postoperative deformation, and absence of vessels in the target location. Various
      methods adapted from percutaneous coronary artery intervention can be applied to
      resolve these problems and ensure a good lead position.

PMID- 19170925
TI  - A unique plasma proteomic profiling with imbalanced fibrinogen cascade in
      patients with Kawasaki disease.
AB  - Kawasaki disease (KD) is the leading cause of acquired heart disease during
      childhood in the developed countries. The mechanism and biomarkers of KD remain
      to be determined. In this study, we sought to elucidate potential plasma
      proteomic markers in KD patients in comparison to that in febrile controls.
      Plasma samples from KD patients and febrile controls were subjected to two
      dimensional polyacrylamide gel electrophoresis analysis. Differential protein
      displays between KD patients and febrile controls were determined. Fibrinogen
      beta and gamma chains, alpha-1-antitrypsin (A1AT), CD5 antigen-like precursor
      (CD5L), and clusterin were increased in KD patients, whereas immunoglobulin free
      light chains were decreased, as compared with controls. The differential protein
      displays were validated with enzyme-linked immunosorbent assay tests. We found
      higher fibrinogen-related proteins (fibrinogen, A1AT, clusterin, and CD5L), along
      with a lower level of the immunoglobulin free light chains that involve fibrin
      degradation in KD. Results from this study showing a unique proteomic profiling
      with abnormal fibrinogen cascade may afford a good biomarker of KD and a better
      strategy to prevent cardiovascular complications of KD by correcting abnormal
      fibrin deposition or degradation.

PMID- 19170926
TI  - Strategies to treat children with end-stage renal dysfunction and severe lower
      urinary tract anomalies for receiving a kidney transplant.
AB  - Dealing with children with bladder dysfunction and kidney transplant is certainly
      not a new issue. Nevertheless, it is still a matter of discussion and dilemma,
      based on few, not standardized, institutional center experiences. The authors
      perform a review of the techniques employed to restore the bladder condition in
      terms of storage and drainage of urine to receive a kidney transplant in a safer
      condition. Aspects of the etiology and the way of evaluation of such a group of
      patients are discussed. The strategies and individualized therapeutic options are
      presented and compared with the author's experience based upon 25 children with
      urinary anomalies who received 28 kidney transplants. Nevertheless, the number of
      complications, mainly UTI, graft and patient survival rates are equivalent to the
      group of children with non-urological causes of ESRD. Patients with severe lower
      urinary tract abnormalities and ESRD may receive a kidney transplant with
      comparable success.

PMID- 19170927
TI  - Renal transplant donation from a deceased cardiac graft recipient: a case for
      marginal donors.
AB  - We describe a case of dual kidney transplant in a highly sensitized 18-yr-old
      male patient followed for chronic renal failure secondary to focal and segmental
      glomerulosclerosis. The donor was a six-yr-old boy who had received a cardiac
      transplant at the age of three months and had been treated with CNIs for over
      five yr. Renal biopsy performed before the transplant revealed focal sclerosis in
      30-40% of the donor's glomeruli. Considering the long expected time on the
      waiting list for this highly sensitized boy and the absence of prohibited
      antigens in the donor, we decided to perform the transplant. To increase renal
      mass, both kidneys were transplanted. Clinical course was good but the patient
      developed proteinuria, which improved with ramipril. We performed two renal
      biopsies in the first nine months post-transplant which showed a progressive
      increase of the glomerulosclerosis. Despite the histology, renal function remains
      good 24 months after transplant. This is the first report of a transplant using a
      kidney from a donor who had received long-term CNI treatment. Short-term outcome
      is satisfactory. We suggest that marginal donors could also be considered for
      donation in pediatric age for selected groups of patients.

PMID- 19170928
TI  - Urinary tract infections in pediatric renal transplant recipients--a two center
      risk factors study.
AB  - UTI are common in renal Tx recipients and may significantly impact on the graft
      function. The aim of our study was to evaluate the prevalence, risk factors, and
      significance of UTI in Tx children. We performed a retrospective cross-sectional
      study of 76 Tx patients, median age at Tx was 13.4 yr. Twenty-one of 76 (28%)
      patients developed at least one UTI during the mean follow-up time of 3.3 +/- 2.0
      yr post-Tx. The first UTI occurred at a median of 160 days post-Tx. The RR of
      having UTI was significantly higher in patients with the primary diagnosis of
      obstructive uropathy (RR = 2.6, 95th CI = 1.1-6.0, p = 0.032), history of PN pre
      Tx (RR = 2.7, 95th CI = 1.3-5.4, p = 0.009) and pre Tx VUR (RR = 2.2, 95th CI =
      1.1-4.5, p = 0.045). These three factors also significantly decreased the
      infection-free survival time to the first UTI. Most UTI caused reversible acute
      allograft dysfunction, but the long-term graft function could not be reliably
      assessed with SCr. In conclusion, UTI occurred in 28% of pediatric Tx recipients,
      mostly during the first year post-Tx despite antibiotic prophylaxis. The
      diagnosis of obstructive uropathy, history of UTI and VUR prior to Tx were
      significant risk factors.

PMID- 19170929
TI  - Successful ABO-incompatible heart transplantation in a child despite blood-group
      sensitization after ventricular assist device support.
AB  - In the first two yr of life blood-group incompatible (ABO-incompatible) heart
      transplantation can be performed leading to immune tolerance to donor blood
      group. Antibody titers should be below 1:4. VAD use is correlated with
      sensitization toward blood-group antigens. A boy was diagnosed with dilated
      cardiomyopathy at nine months of age and listed for 0-compatible transplantation.
      Progressive heart failure required implantation of a left VAD. His listing was
      extended for ABO-incompatible transplantation despite antibody titers of 1:32
      anti-A and 1:8 anti-B. After 26 days on VAD, he was transplanted with a B donor
      heart. No hyperacute or acute rejection occurred in 12 months post-transplant.
      Anti-B antibodies rose to a maximum of 1:2. No use of rituximab or plasmapheresis
      was required. There are no signs of graft vasculopathy. This indicates that
      inclusion criteria for ABO-incompatible transplantation may be extended to
      immediate cases. This is the first case with a healthy immune system to show
      signs of tolerance development after ABO-incompatible heart transplantation with
      increased prior antibody titers and without specific treatment.

PMID- 19170930
TI  - Successful treatment of influenza A virus by oseltamivir in bone marrow
      transplant recipients.
AB  - INFVA is an important cause of pulmonary infections in patients receiving BMT,
      and is associated with considerable morbidity and mortality for a readily
      preventable and treatable infection. Few studies have addressed the impact of the
      new neuraminidase inhibitors in the prognosis of influenza after BMT. The aim of
      this study is to assess the impact of oseltamivir on the control of INFVA
      infection in BMT recipients. INFVA was screened in NPA and/or bronchoalveolar
      lavage using IF in all BMT recipients having respiratory symptoms. Three URTI and
      one associated upper and LRTI were diagnosed in three BMT recipients out of six
      patients admitted to the BMT unit, during eight-wk period (March and April 2008).
      All patients having INFVA respiratory infection were treated by oral oseltamivir
      60 mg/day, begun more than 48 h after symptom onset. Respiratory symptoms
      disappeared within a mean of 60 h (48-96 h) of treatment. However, viral tests
      had remained positive for 8-39 days. Outside the initial associated URTI and
      LRTI, no further viral pneumonia occurred. No patient died of INFVA. Oseltamivir
      was well tolerated outside vomiting during the first three days of treatment in
      one patient. Oseltamivir appears to play an important role in the outcome of
      INFVA infection as well in URTI as in severe LRTI in patients receiving BMT.

PMID- 19170931
TI  - Nonlinear absorption microscopy.
AB  - For the past two decades, nonlinear microscopy has been developed to overcome the
      scattering problem in thick tissue imaging. Owing to its increased imaging depth
      and high spatial resolution, nonlinear microscopy becomes the first choice for
      imaging living tissues. The use of nonlinear optical effects not only facilitates
      the signal originating from an extremely small volume defined by light focusing
      but also provides novel contrast mechanisms with molecular specificity. Nonlinear
      absorption is a nonlinear optical effect in which the absorption coefficient
      depends on excitation intensity. As a commonly used spectroscopy tool, nonlinear
      absorption measurement uncovers many photophysical and photochemical processes
      correlated with electronic states of molecules. Recently we have been focusing on
      adapting this spectroscopy method to a microscopy imaging technique. The effort
      leads to a novel modality in nonlinear microscopy-nonlinear absorption
      microscopy. This article summarizes the principles and instrumentation of this
      imaging technique and highlights some of the recent progress in applying it to
      imaging skin pigmentation and microvasculature under ex vivo or in vivo
      conditions.

PMID- 19170932
TI  - The chloroplast protein RPH1 plays a role in the immune response of Arabidopsis
      to Phytophthora brassicae.
AB  - Plant immune responses to pathogens are often associated with enhanced production
      of reactive oxygen species (ROS), known as the oxidative burst, and with rapid
      hypersensitive host cell death (the hypersensitive response, HR) at sites of
      attempted infection. It is generally accepted that the oxidative burst acts as a
      promotive signal for HR, and that HR is highly correlated with efficient disease
      resistance. We have identified the Arabidopsis mutant rph1 (resistance to
      Phytophthora 1), which is susceptible to the oomycete pathogen Phytophthora
      brassicae despite rapid induction of HR. The susceptibility of rph1 was specific
      for P. brassicae and coincided with a reduced oxidative burst, a runaway cell
      death response, and failure to properly activate the expression of defence
      related genes. From these results, we conclude that, in the immune response to P.
      brassicae, (i) HR is not sufficient to stop the pathogen, (ii) HR initiation can
      occur in the absence of a major oxidative burst, (iii) the oxidative burst plays
      a role in limiting the spread of cell death, and (iv) RPH1 is a positive
      regulator of the P. brassicae-induced oxidative burst and enhanced expression of
      defence-related genes. Surprisingly, RPH1 encodes an evolutionary highly
      conserved chloroplast protein, indicating a function of this organelle in
      activation of a subset of immune reactions in response to P. brassicae. The
      disease resistance-related role of RPH1 was not limited to the Arabidopsis model
      system. Silencing of the potato homolog StRPH1 in a resistant potato cultivar
      caused susceptibility to the late blight pathogen Phytophthora infestans.

PMID- 19170933
TI  - Arabidopsis MYB30 is a direct target of BES1 and cooperates with BES1 to regulate
      brassinosteroid-induced gene expression.
AB  - A paradox of plant hormone biology is how a single small molecule can affect a
      diverse array of growth and developmental processes. For instance,
      brassinosteroids (BRs) regulate cell elongation, vascular differentiation,
      senescence and stress responses. BRs signal through the BES1/BZR1 (bri1
      Ethylmethane Sulphonate suppressor 1/brassinazole-resistant 1) family of
      transcription factors, which regulate hundreds of target genes involved in this
      pathway, yet little is known of this transcriptional network. Through microarray
      and chromatin immunoprecipitation (ChIP) experiments, we identified a direct
      target gene of BES1, AtMYB30, which encodes an MYB family transcription factor.
      AtMYB30 null mutants display decreased BR responses and enhance the dwarf
      phenotype of a weak allele of the BR receptor mutant bri1. Many BR-regulated
      genes have reduced expression and/or hormone-induction in AtMYB30 mutants,
      indicating that AtMYB30 functions to promote expression of a subset of BR target
      genes. AtMYB30 and BES1 bind to a conserved MYB-binding site and E-box sequences,
      respectively, in the promoters of genes that are regulated by both BRs and
      AtMYB30. Finally, AtMYB30 and BES1 interact with each other both in vitro and in
      vivo. These results demonstrate that BES1 and AtMYB30 function cooperatively to
      promote BR target gene expression. Our results therefore establish a new
      mechanism by which AtMYB30, a direct target of BES1, functions to amplify BR
      signaling by helping BES1 activate downstream target genes.

PMID- 19170934
TI  - The nucleotidase/phosphatase SAL1 is a negative regulator of drought tolerance in
      Arabidopsis.
AB  - An Arabidopsis thaliana drought-tolerant mutant, altered expression of APX2
      (alx8), has constitutively increased abscisic acid (ABA) content, increased
      expression of genes responsive to high light stress and is reported to be drought
      tolerant. We have identified alx8 as a mutation in SAL1, an enzyme that can
      dephosphorylate dinucleotide phosphates or inositol phosphates. Previously
      identified mutations in SAL1, including fiery (fry1-1), were reported as being
      more sensitive to drought imposed by detachment of rosettes. Here we demonstrate
      that alx8, fry1-1 and a T-DNA insertional knockout allele all have markedly
      increased resistance to drought when water is withheld from soil-grown intact
      plants. Microarray analysis revealed constitutively altered expression of more
      than 1800 genes in both alx8 and fry1-1. The up-regulated genes included some
      characterized stress response genes, but few are inducible by ABA. Metabolomic
      analysis revealed that both mutants exhibit a similar, dramatic reprogramming of
      metabolism, including increased levels of the polyamine putrescine implicated in
      stress tolerance, and the accumulation of a number of unknown, potential
      osmoprotectant carbohydrate derivatives. Under well-watered conditions, there was
      no substantial difference between alx8 and Col-0 in biomass at maturity; plant
      water use efficiency (WUE) as measured by carbon isotope discrimination; or
      stomatal index, morphology or aperture. Thus, SAL1 acts as a negative regulator
      of predominantly ABA-independent and also ABA-dependent stress response pathways,
      such that its inactivation results in altered osmoprotectants, higher leaf
      relative water content and maintenance of viable tissues during prolonged water
      stress.

PMID- 19170935
TI  - What I was doing versus what I did: verb aspect influences memory and future
      actions.
AB  - This research examined whether describing past actions as ongoing using the
      imperfective aspect (rather than describing them as completed using the
      perfective aspect) promotes memory for action-relevant knowledge and reenactment
      of these actions in a future context. In Experiment 1, participants who used the
      imperfective aspect to describe their strategy on a prior interpersonal task were
      more likely to use this strategy on a later task than were participants who used
      the perfective aspect to describe their prior strategy. Experiment 2 demonstrated
      that describing behaviors on a task using the imperfective rather than the
      perfective aspect increased willingness to resume that task by improving memory
      for task contents. The last two experiments showed that the effects of the
      imperfective aspect on memory decayed over time and that the imperfective aspect
      facilitated performance of a future behavior only when the described past
      behavior was relevant to the future behavior. Thus, the effects of aspect are
      moderated by memory decay and are behavior-specific.

PMID- 19170936
TI  - Stimulus-specific delay activity in human primary visual cortex.
AB  - Working memory (WM) involves maintaining information in an on-line state. One
      emerging view is that information in WM is maintained via sensory recruitment,
      such that information is stored via sustained activity in the sensory areas that
      encode the to-be-remembered information. Using functional magnetic resonance
      imaging, we observed that key sensory regions such as primary visual cortex (V1)
      showed little evidence of sustained increases in mean activation during a WM
      delay period, though such amplitude increases have typically been used to
      determine whether a region is involved in on-line maintenance. However, a
      multivoxel pattern analysis of delay-period activity revealed a sustained pattern
      of activation in V1 that represented only the intentionally stored feature of a
      multifeature object. Moreover, the pattern of delay activity was qualitatively
      similar to that observed during the discrimination of sensory stimuli, suggesting
      that WM representations in V1 are reasonable "copies" of those evoked during pure
      sensory processing.

PMID- 19170937
TI  - The wisdom of many in one mind: improving individual judgments with dialectical
      bootstrapping.
AB  - The "wisdom of crowds" in making judgments about the future or other unknown
      events is well established. The average quantitative estimate of a group of
      individuals is consistently more accurate than the typical estimate, and is
      sometimes even the best estimate. Although individuals' estimates may be riddled
      with errors, averaging them boosts accuracy because both systematic and random
      errors tend to cancel out across individuals. We propose exploiting the power of
      averaging to improve estimates generated by a single person by using an approach
      we call dialectical bootstrapping. Specifically, it should be possible to reduce
      a person's error by averaging his or her first estimate with a second one that
      harks back to somewhat different knowledge. We derive conditions under which
      dialectical bootstrapping fosters accuracy and provide an empirical demonstration
      that its benefits go beyond reliability gains. A single mind can thus simulate
      the wisdom of many.

PMID- 19170938
TI  - Religion and support for suicide attacks.
AB  - In four studies carried out across different cultural, religious, and political
      contexts, we investigated the association between religion and popular support
      for suicide attacks. In two surveys of Palestinians and one cognitive priming
      experiment with Israeli settlers, prayer to God, an index of religious devotion,
      was unrelated to support for suicide attacks. Instead, attendance at religious
      services, thought to enhance coalitional commitment, positively predicted support
      for suicide attacks. In a survey of six religions in six nations, regular
      attendance at religious services positively predicted a combination of willing
      martyrdom and out-group hostility, but regular prayer did not. Implications for
      understanding the role of religion in suicide attacks are discussed.

PMID- 19170939
TI  - Counteractive self-control.
AB  - We propose a self-control analysis of the role of availability in valuation. We
      explored the hypothesis that, when temptation becomes available, counteractive
      self-control processes render it less valuable. We found evidence for devaluation
      of available temptation among gym users before they choose to forgo an unhealthy
      snack rather than after they make their choice (Study 1), and among students
      evaluating leisure activities when their decision to enroll in an uninteresting
      class is reversible rather than irreversible (Study 2).

PMID- 19170940
TI  - Males' greater tolerance of same-sex peers.
AB  - Three studies were conducted to examine the often-cited conclusion that human
      females are more sociable than males. Using perceptions of roommates, roommate
      changes at three collegiate institutions, and an experimental manipulation of
      friendship beliefs, the studies demonstrated unequivocally that males exhibit a
      higher threshold of tolerance for genetically unrelated same-sex individuals than
      females do. Tolerance was defined as acceptance of the stresses and strains
      within relationships. Results are discussed in terms of potential underlying
      mechanisms and ultimate explanations.

PMID- 19170941
TI  - If it's difficult to pronounce, it must be risky.
AB  - Low processing fluency fosters the impression that a stimulus is unfamiliar,
      which in turn results in perceptions of higher risk, independent of whether the
      risk is desirable or undesirable. In Studies 1 and 2, ostensible food additives
      were rated as more harmful when their names were difficult to pronounce than when
      their names were easy to pronounce; mediation analyses indicated that this effect
      was mediated by the perceived novelty of the substance. In Study 3, amusement
      park rides were rated as more likely to make one sick (an undesirable risk) and
      also as more exciting and adventurous (a desirable risk) when their names were
      difficult to pronounce than when their names were easy to pronounce.

PMID- 19170942
TI  - Liberating effects of losing executive control.
AB  - Across numerous domains, research has consistently linked decreased capacity for
      executive control to negative outcomes. Under some conditions, however, this
      deficit may translate into gains: When individuals' regulatory strategies are
      maladaptive, depletion of the resource fueling such strategies may facilitate
      positive outcomes, both intra- and interpersonally. We tested this prediction in
      the context of contentious intergroup interaction, a domain characterized by
      regulatory practices of questionable utility. White participants discussed
      approaches to campus diversity with a White or Black partner immediately after
      performing a depleting or control computer task. In intergroup encounters,
      depleted participants enjoyed the interaction more, exhibited less inhibited
      behavior, and seemed less prejudiced to Black observers than did control
      participants--converging evidence of beneficial effects. Although executive
      capacity typically sustains optimal functioning, these results indicate that, in
      some cases, it also can obstruct positive outcomes, not to mention the potential
      for open dialogue regarding divisive social issues.

PMID- 19170943
TI  - Helpful only in the abstract?
AB  - This study tested the hypothesis that empathizing with out-group members is
      beneficial outside of, but not within, intergroup-contact situations. We
      predicted that in the context of intergroup interaction, the potential for
      evaluation would lead individuals' perspective-taking efforts to take on an
      egocentric and counterproductive flavor. As predicted, when empathy was
      instantiated during an intergroup exchange, it failed to exert its usual positive
      effect on intergroup attitudes and led higher-prejudice individuals to derogate
      an out-group member who was an interaction partner; empathy also blocked the
      prejudice-reducing influence of intergroup contact. Mediation analyses indicated
      that activation of negative metastereotypes regarding the out-group's view of the
      in-group accounted for these effects. The findings, which demonstrate ironic
      effects of empathy in intergroup interaction, indicate that interventions based
      on studies of individuals' reactions to out-group members in the abstract might
      have dramatically different consequences when put into practice in real exchanges
      between members of different groups.

PMID- 19170944
TI  - Fear-related chemosignals modulate recognition of fear in ambiguous facial
      expressions.
AB  - Integrating emotional cues from different senses is critical for adaptive
      behavior. Much of the evidence on cross-modal perception of emotions has come
      from studies of vision and audition. This research has shown that an emotion
      signaled by one sense modulates how the same emotion is perceived in another
      sense, especially when the input to the latter sense is ambiguous. We tested
      whether olfaction causes similar sensory modulation of emotion perception. In two
      experiments, the chemosignal of fearful sweat biased women toward interpreting
      ambiguous expressions as more fearful, but had no effect when the facial emotion
      was more discernible. Our findings provide direct behavioral evidence that social
      chemosignals can communicate emotions and demonstrate that fear-related
      chemosignals modulate humans' visual emotion perception in an emotion-specific
      way--an effect that has been hitherto unsuspected.

PMID- 19170945
TI  - Psychophysiological outcomes of health qigong for chronic conditions: a
      systematic review.
AB  - We aimed to unravel the clinical benefits and the plausible underlying
      psychophysiological mechanism based on available randomized controlled trials
      (RCTs). Meta-analysis of 26 RCTs shortlisted from electronic databases from 1997
      to 2006 shows that qigong had some effects on increasing the numbers of white
      blood cells and lymphocytes, stroke volume, peak early transmitral filling
      velocity, peak late transmitral filling velocity, forced vital capacity, and
      forced expiratory volume, and, conversely, lowering of total cholesterol,
      systolic blood pressure, diastolic blood pressure, and depressive mood scores.
      Explanatory pathways may pertain to stress reduction via nervous, endocrine, and
      immune systems. Limitations on methodology are discussed and directions for
      further studies are suggested. Because of its safety, minimal cost, and clinical
      benefit, health qigong can be advocated as an adjunctive exercise therapy for
      older people with chronic conditions.

PMID- 19170946
TI  - An auditory oddball (P300) spelling system for brain-computer interfaces.
AB  - This study was designed to develop and test an auditory event-related potential
      (ERP) based spelling system for a brain-computer interface (BCI) and to compare
      user's performance between the auditory and visual modality. The spelling system,
      where letters in a matrix were coded with acoustically presented numbers, was
      tested on a group of healthy volunteers. The results were compared with a visual
      spelling system. Nine of the 13 participants presented with the auditory ERP
      spelling system scored above a predefined criterion level control for
      communication. Compared to the visual spelling system, users' performance was
      lower and the peak latencies of the auditorily evoked ERPs were delayed. It was
      concluded that auditorily evoked ERPs from the majority of the users could be
      reliably classified. High accuracies were achieved in these users, rendering item
      selection with a BCI based on auditory stimulation feasible for communication.

PMID- 19170947
TI  - Age, physical fitness, and attention: P3a and P3b.
AB  - The influence of age and fitness on the neuroelectric correlates of attentional
      orienting and processing during stimulus discrimination were investigated.
      Younger and older adult participants completed a maximal aerobic exercise test
      and were separated into higher- and lower-fit groups according to their
      cardiorespiratory fitness. Task performance and event-related potential measures
      were obtained during two- and three-stimulus oddball tasks. Results indicated
      that fitness may ameliorate or protect against cognitive aging for simple
      stimulus discriminations. Increases in task difficulty indicated that fitness may
      not be sufficient to overcome age-related deficits in stimulus discrimination.
      Further, fitness did not influence attentional orienting. The findings suggest
      that fitness-related changes in cognitive function may originate from other
      attentional mechanisms. Theoretical implications are discussed.

PMID- 19170948
TI  - Within-individual discrimination on the Concealed Information Test using dynamic
      mixture modeling.
AB  - Whether an examinee has information about a crime is determined by the Concealed
      Information Test based on autonomic differences between the crime-related item
      and other control items. Multivariate quantitative statistical methods have been
      proposed for this determination. However, these require specific databases of
      responses, which are problematic for field application. Alternative methods,
      using only an individual's data, are preferable, but traditionally such within
      individual approaches have limitations because of small data sample size. The
      present study proposes a new within-individual judgment method, the hidden Markov
      discrimination method, in which time series-data are modeled with dynamic mixture
      distributions. This method was applied to experimental data and showed sufficient
      potential in discriminating guilty from innocent examinees in a mock theft
      experiment compared with performance of previous methods.

PMID- 19170949
TI  - Prolonged platelet activation in individuals with elevated blood pressure in
      response to a moderate exercise challenge.
AB  - We examined the magnitude of 20-min moderate exercise-induced platelet activation
      in 50 volunteers with normal (n=31) or elevated blood pressure (EBP; n=19). Blood
      was drawn before, immediately after, and 25 min after exercise. Antibody-staining
      for platelet activation markers, P-selectin, and fibrinogen receptors was done
      with and without adenosine diphosphate (ADP) stimulation in whole blood for flow
      cytometric analyses. Exercise led to increases in percent aggregated platelets
      and percent platelets expressing P-selectin or PAC-1 binding (ps< or =.001). This
      increase in percent platelets expressing P-selectin continued even after a 25-min
      rest only in the EBP group (p< or =.01) accompanied by an increase in percent of
      aggregated platelets (p< or =.05). Although ADP stimulation led to increased
      platelet activation at rest, it was attenuated following exercise, even among EBP
      individuals. A moderate exercise challenge induced prolonged platelet activation
      in individuals with EBP but attenuation in activation to further stimulation by
      an agonist. Findings suggest that a recovery period after physical stress appears
      critical in individuals with high BP regarding platelet activation and
      aggregation, which can lead to an acute coronary syndrome in vulnerable
      individuals.

PMID- 19170950
TI  - Tracking the voluntary control of auditory spatial attention with event-related
      brain potentials.
AB  - A lateralized event-related potential (ERP) component elicited by attention
      directing cues (ADAN) has been linked to frontal-lobe control but is often absent
      when spatial attention is deployed in the auditory modality. Here, we tested the
      hypothesis that ERP activity associated with frontal-lobe control of auditory
      spatial attention is distributed bilaterally by comparing ERPs elicited by
      attention-directing cues and neutral cues in a unimodal auditory task. This
      revealed an initial ERP positivity over the anterior scalp and a later ERP
      negativity over the parietal scalp. Distributed source analysis indicated that
      the anterior positivity was generated primarily in bilateral prefrontal cortices,
      whereas the more posterior negativity was generated in parietal and temporal
      cortices. The anterior ERP positivity likely reflects frontal-lobe attentional
      control, whereas the subsequent ERP negativity likely reflects anticipatory
      biasing of activity in auditory cortex.

PMID- 19170951
TI  - Phenotypic and genetic correlations between evoked EEG/ERP measures during the
      response anticipation period of a delayed response task.
AB  - We investigated the relationship between three electrophysiological indices of
      response anticipation in a spatial delayed response task with a low and high
      memory load manipulation: a slow cortical potential (SCP), theta
      desynchronization, and upper alpha synchronization. Individual differences in
      these three measures were examined in 531 adult twins and siblings. Heritability
      of the SCP at occipital-parietal leads varied from 30% to 43%. Heritability of
      upper alpha synchronization (35% to 65%) and theta desynchronization (31% to 50%)
      was significant at all leads. Theta desynchronization and upper alpha
      synchronization were significantly correlated (r approximately 43%), but SCP was
      not correlated with either. The effect of working memory load on all three
      measures was not heritable. Response anticipation reliably evokes an SCP, upper
      alpha synchronization and theta desynchronization, but variation in these
      measures reflects different (genetic) sources.

PMID- 19170952
TI  - Improving the performance of physiologic hot flash measures with support vector
      machines.
AB  - Hot flashes are experienced by over 70% of menopausal women. Criteria to classify
      hot flashes from physiologic signals show variable performance. The primary aim
      was to compare conventional criteria to Support Vector Machines (SVMs), an
      advanced machine learning method, to classify hot flashes from sternal skin
      conductance. Thirty women with > or =4 hot flashes/day underwent laboratory hot
      flash testing with skin conductance measurement. Hot flashes were quantified with
      conventional (> or =2 micromho, 30 s) and SVM methods. Conventional methods had
      poor sensitivity (sensitivity=0.41, specificity=1, positive predictive value
      (PPV)=0.94, negative predictive value (NPV)=0.85) in classifying hot flashes,
      with poorest performance among women with high body mass index or anxiety. SVM
      models showed improved performance (sensitivity=0.89, specificity=0.96, PPV=0.85,
      NPV=0.96). SVM may improve the performance of skin conductance measures of hot
      flashes.

PMID- 19170953
TI  - Reproductive development of Santa Ines rams during the first year of life: body
      and testis growth, testosterone concentrations, sperm parameters, age at puberty
      and seminal plasma proteins.
AB  - We have investigated the reproductive development of the tropically adapted Santa
      Ines ram, the most common hair sheep in Brazil. From 8 to 48 weeks of age, 16
      animals were evaluated for body and testis growth, semen parameters, testosterone
      concentrations and seminal plasma proteins, using two-dimensional SDS-PAGE.
      Animals were weaned at 30 days and kept in feedlots thereafter, receiving hay,
      concentrate (18% of crude protein) and mineral supplement. Body weight increased
      from 12.3 +/- 0.7 to 54.3 +/- 1.6 kg between 8 and 48 weeks (p < 0.05), but
      changes in thoracic perimeter and scrotal circumference were non-significant
      after 36 weeks (p > 0.05). The percentage of motile sperm increased slowly until
      23 weeks and more rapidly after that age, but significant changes in progressive
      motility occurred after 25 weeks. Presence of abnormal sperm related inversely to
      age. Most significant changes in sperm concentration occurred between 38 and 44
      weeks (0.38 +/- 0.05 to 1.14 +/- 0.24 x 10(9) cells/ml, p < 0.05) and
      testosterone reached its highest concentrations at 42 weeks, decreasing
      afterwards. Rams reached puberty at 28.2 +/- 0.8 weeks. The number of protein
      spots on seminal plasma gels was similar from 15 to 18 weeks (45 and 47 spots; p
      > 0.05), increased until 24 weeks (141 spots) and 28 weeks (170 spots; p < 0.05)
      and remained without significant (p > 0.05) changes from 28 to 48 weeks (186 +/-
      10 spots). Furthermore, the intensity of selected spots on 2D maps increased (p <
      0.05) between 15 and 28 weeks, which preceded or coincided with the main
      developmental changes in sperm motility and percentage of defective sperm in the
      ejaculates. These results will support future studies designed to characterize
      specific seminal plasma proteins whose expression relate to the development of
      testis, epididymis and accessory sex glands.

PMID- 19170954
TI  - From the very public to the less known.

PMID- 19170955
TI  - The psychometric study of the Serbian KINDL questionnaire for health-related
      quality of life assessment in children and adolescents.
AB  - OBJECTIVES: Health-related quality of life (HRQOL) is the most frequently
      evaluated patient-reported outcome. It is unexplored in Serbia and there are no
      methods for its evaluation. This study was aimed to analyse the psychometric
      properties of the Serbian version of the KINDL questionnaire for HRQOL assessment
      in children and adolescents. METHODS: The KINDL-Kid-S completed 100 children and
      the KINDL-Kiddo-S 92 adolescents. Both versions were descriptively analysed and
      explored the items-sub-scales relationships. Cronbach's coefficient was used to
      explore the reliability of the versions. RESULTS: The means of all sub-scales
      were located on the positive side of the response scale. The total score was
      78.84 for the KINDL-Kid-S and 75.51 for the KINDL-Kiddo-S. Within the versions,
      the items showed significant correlations with its sub-scale total score and the
      total score. Between the sub-scales, there were significant relationships also.
      The Cronbach's coefficient exceeded 0.8 for the internal consistency reliability
      of the total score in both, and ranged 0.45-0.7 for the sub-scales. CONCLUSIONS:
      Besides substantial inter- and intra-sub-scale correlations, the reliability
      coefficients of some sub-scales are low in the Serbian KINDL, emerging the needs
      for revisions before extensive uses.

PMID- 19170956
TI  - Can a focused staff training programme improve the ward atmosphere and patient
      satisfaction in a forensic psychiatric hospital? A pilot study.
AB  - OBJECTIVE: The main aim of the study was to describe whether staff training and
      lectures on milieu therapy to nursing staff can change the treatment environment,
      as perceived by the patients, in a desirable direction. The study was approved by
      the Regional Ethics Committee for Medical Research. METHOD: To measure the
      patients' perceptions of the treatment environment we used the Ward Atmosphere
      Scale (WAS). The ward atmosphere was evaluated three times during a 12-month
      period. Additionally, the patients completed five questions concerning
      satisfaction with the treatment environment. Between the first and the second
      ward evaluation the nursing staff was given 3 weeks of lectures on different
      aspects of milieu therapy. The nursing staff completed the WAS and three
      satisfaction items. RESULTS: The study revealed a change in desired direction
      after education in five of the six key subscales of the WAS (Involvement,
      Support, Practical orientation, Angry and aggressive behaviour and Order and
      organization). Staff control was the only subscale with no changes. The patients
      also reported an increase in satisfaction. The study revealed no major changes in
      the staff scores. The present study included only a small number of patients and
      examined the changes in only one psychiatric department; hence it could be argued
      that the results cannot be generalized to equivalent populations within the
      forensic services. CONCLUSIONS: The study indicated that it is possible to
      improve the ward atmosphere in a desirable direction by a 3-week training
      programme for nursing staff about important aspects of milieu therapy.

PMID- 19170957
TI  - Meanings of staying healthy in a context where others developed burnout-
      phenomenological-hermeneutic interpretation of healthcare personnel's narratives.
AB  - Burnout has become a major problem in many industrialized countries, but not
      everyone at the same work place develops burnout. The present paper aimed to
      illuminate meanings of staying healthy in a context where others developed
      burnout as narrated by healthcare personnel. Interviews were conducted with 20
      healthcare personnel and were interpreted using a phenomenological-hermeneutic
      method. The result shows that the meanings of staying healthy are to be rooted in
      an outlook on life perceiving its many-sidedness and the strengths and weaknesses
      of oneself and others with forbearance. One is striving to shoulder
      responsibility for oneself and for others and is also receptive towards the
      circumstances of life, striving to judge the possibilities of being and acting in
      order to attempt to influence things in what is believed to be the right
      direction. Being able to let go of injustice and look after oneself with a clear
      conscience is also revealed as meanings of staying healthy. In conclusion,
      forbearance with life's many-sidedness seems to pervade one's experiences,
      judgements and actions in life when dealing with one's reality, and thus, it is
      interpreted as essential for staying healthy in a context where others developed
      burnout. This study is ethically approved.

PMID- 19170958
TI  - Early abortion as narrated by young Swedish women.
AB  - AIM: The aim of the study was to illuminate meanings of having had an induced
      abortion among young Swedish women. METHODS: Narrative interviews were conducted
      with ten 18-20-year-old women 2-6 weeks after a medical or surgical abortion in
      the sixth to twelfth week of pregnancy. Data were analysed according to a
      phenomenological hermeneutic method. RESULTS: The study disclosed a multitude of
      complex meanings in the young women's lived experiences of induced abortion. Four
      themes were revealed: having cared for and protected the unimagined pregnancy,
      taking the life of my child-to-be with pain, being sensitive to the approval of
      others and imagining the taken away child-to-be. The results are discussed in
      light of Nussbaum's theory of development ethics. The young women's ability to be
      responsible for their choices regarding their own welfare and others' well-being
      in a life cycle perspective was disclosed, despite the pain inherent in the
      responsibility of taking the life of their own child-to-be. CONCLUSIONS: The
      young women's narratives were replete with ethical reasoning regarding
      existential matters related to their responsibility of choosing between induced
      abortion and parenthood and how to live their lives with this experience. Health
      care professionals could promote young women's capability to be responsible, as
      well as the development of trust in their own fertility and constructive
      relationships with significant others. In the development of the prevention of
      unintended pregnancies and the sexual education of young people in Sweden
      existential dimensions of undergoing an abortion should be given attention.

PMID- 19170959
TI  - Mammography screening from the perspective of quality of life: a review of the
      literature.
AB  - AIMS: The purpose of this literature review was to explore how women attending a
      national mammography screening programme reacted to the screening process on
      quality of life (QoL). The research question was what implications regarding true
      negative results and false-positive results from mammography screening were found
      among women? Quality of life including life domains as psychological, physical
      and social was the theoretical reference in the study. METHOD: Guided by the
      concept of QoL on mammography screening a database search of Medline, Cinahl and
      Cochrane was carried out. Search terms such as QoL, anxiety and mammography have
      been used. FINDINGS: A review of studies between 1995 and 2007 showed that the
      implications regarding a negative result were less than those regarding false
      positive one. It was found that women with negative results after mammography
      screening experience minor negative psychological consequences, and some women
      have even measured less anxiety following mammography than before because of the
      reassurance given by a clear negative result. False-positive result and recalls
      were a problem for many women. The process following recalls do affect women
      emotionally, decrease their wellbeing and QoL for weeks and even months.
      CONCLUSION: Future research should be directed at measuring the short-term
      outcomes in representative populations for whom screening and prevention are
      indicated. This knowledge would be useful for the organisation of the mammography
      programmes and for communication with the general population, the women coming
      for screening and those who do not attend.

PMID- 19170960
TI  - Implementation of a nutritional programme in elderly people admitted to resident
      homes.
AB  - AIM: The aim was to test the hypothesis that education provided to staff
      regarding nutritional needs and individualizing nutritional care will improve the
      nutritional status and functional capacity of elderly people newly admitted to
      resident homes. DESIGN: Pre- and posttest, quasi experimental. SETTING: Resident
      homes. SUBJECTS: Sixty-two residents (20 men, 42 women) in the experimental group
      and 53 (14 men, 39 women) in the control group were consecutively included. Mean
      age was 85 years. METHODS: On admission and after 4 months, nutritional status
      was assessed using a combination of anthropometry (weight index, arm muscle
      circumference and triceps skinfold thickness) and biochemical measurements (serum
      albumin and transthyretin). Functional capacity and overall cognitive function
      were also assessed. In the experimental unit, the staff received education about
      nutritional needs and individualized nutritional care. RESULTS: After 4 months
      the number of residents assessed as protein energy malnourished decreased from 20
      to seven in the experimental (p = 0.004), and from 17 to 10 in the control group
      (p = 0.1). In the experimental group, motor activity (p = 0.006) and cognitive
      function (p = 0.02) increased. In the control group, motor activity decreased (p
      = 0.02). CONCLUSIONS: The results indicate that the intervention had effects, as
      the number of protein energy malnourished residents decreased in the experimental
      group and motor activity and cognitive function improved. No such improvements
      were seen in the control group.

PMID- 19170961
TI  - Nandrolone excretion in sedentary vs physically trained young women.
AB  - We investigated the effects of the menstrual cycle, oral contraception and
      physical training on exhaustive exercise-induced changes in the excretion of
      nandrolone metabolites [19-norandrosterone (19-NA), and 19-noretiocholanolone (19
      NE)] in young women. Twenty-eight women were allocated to an untrained group
      (n=16) or a trained group (n=12), depending on their physical training
      background. The untrained group was composed of nine oral contraceptive users
      (OC+) and seven eumenorrheic women (OC-), while the trained group was entirely
      composed of OC+ subjects. Three laboratory sessions were conducted in a
      randomized order: a prolonged exercise test, a short-term exercise test and a
      control session. Urine specimens were collected before and 30, 60 and 90 min
      after the exercise test and at the same times of the day during the control
      session. Urinary concentrations of nandrolone metabolites were determined by gas
      chromatography coupled to mass spectrometry. Urinary concentrations of 19-NA and
      19-NE ranged from undetectable levels to 1.14 and 0.47 ng/mL, respectively.
      Nandrolone excretion was not affected by the menstrual cycle phase (early
      follicular vs mid-luteal), prior physical training, oral contraception or acute
      physical exercise. Therefore, a urinary concentration of 2 ng/mL of 19-NA appears
      to be fair as the upper acceptable limit in doping control tests for female
      athletes.

PMID- 19170962
TI  - Differential expression of immune genes in Atlantic salmon (Salmo salar L.)
      challenged intraperitoneally or by cohabitation with IPNV.
AB  - Atlantic salmon smolts challenged intraperitoneally (ip) and by cohabitation with
      a highly virulent strain of infectious pancreatic necrosis virus showed strong
      activation of important immune genes in spleen, liver, head-kidney and gill
      measured by real-time quantitative PCR. The genes investigated were IL-1beta, IL
      10, IFN-alpha, IFN-gamma, Mx, MHC-I, MHC-II, TCR-alpha, CD8-alpha and mIgM. A low
      final cumulative mortality of about 10% was seen in the ip-challenged group,
      while more than 40% of the cohabitants died in the sampling period. Sampling was
      performed at day 15, 24 and 37 post ip-challenge. Overall, the expression of the
      investigated genes varied highly. The expression of IL-1beta, IL-10, MHC-II, TCR
      alpha, CD8-alpha and mIgM showed more or less the same patterns between the two
      groups of fish by being significantly upregulated at day 24 post ip-challenge.
      However, the degree of regulation varied a lot among the genes. A pattern showing
      differences between ip-challenged and cohabitants were seen for IFN-gamma and
      especially IFN-alpha, where the upregulation seemed to last longer for the
      cohabitants. The Mx gene was the most induced gene, but also the one with highest
      individual variance. Mx but also MHC-I were both still highly upregulated at the
      last sampling point within both groups of fish. The results seem to indicate that
      the differences in expression pattern(s) could reflect the different routes of
      entrance of the virus into the fish. This could maybe explain the different
      kinetics in the onset and the degree of mortality or the potential different
      molecular mechanisms used for combating the virus.

PMID- 19170963
TI  - A novel anti-inflammatory compound, artonkin-4'-O-glucoside, from the leaves of
      Artocarpus tonkinensis suppresses experimentally induced arthritis.
AB  - Artocarpus tonkinenesis (Moraceae) has been used in Vietnamese traditional
      medicine for the treatment of backache and joint diseases since many 100 years.
      We have previously shown that a crude extract of A. tonkinensis elicited anti
      inflammatory effects in rat collagen-induced arthritis (CIA), with significant
      improvement of disease symptoms. However, the pharmacological basis of the
      bioactivity of A. tonkinensis extract is not known. In the present study, we have
      isolated four individual active components from A. tonkinensis extract by reverse
      phase high-pressure liquid chromatography. The structures of the compounds were
      determined by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry
      and their biological effects investigated. A novel biologically active flavonoid
      glucoside (5-hydroxy-8-hydroxymethyl-8-methyl-2-[4-(3,4,5-trihydroxy-6
      hydroxymethyl-tetrahydro-pyran-2-yloxy)-phenyl]-8H-pyrano[3,2-g]chromen-4-one)
      with an average molecular mass of 514.49 Da was isolated.We have named the
      compound artonkin-4'-O-glucoside. The name 'artonkin' for the novel flavonoid
      part of the compound was coined from the Latin name of its source Artocarpus
      tonkinensis. The three other active flavonoid glucosides isolated and
      characterized were alphitonin-4-O-beta-D-glucoside, maesopsin-4-O-beta-D
      glucoside and kaempherol-3-O-beta-D-glucoside. All four compounds were found to
      cause anti-inflammatory effect with different potencies. The anti-inflammatory
      effects demonstrated in the rat model of arthritis correlate well with the
      inhibition of mitogen-induced T-cell proliferation. Furthermore, the compounds
      inhibit production of cytokines, such as tumour necrosis factor-a and interferon
      c, in mitogen-stimulated T cells in a concentration-dependent manner. We
      postulate that the isolated flavonoids suppress T-cell proliferation as well as
      cytokine expression and thereby contribute to an amelioration of arthritis
      severity in CIA.

PMID- 19170964
TI  - Elevated expression of transmembrane IL-15 in immune cells correlates with the
      development of murine lupus: a potential target for immunotherapy against SLE.
AB  - Presentation in trans by the Interleukin-15 receptor alpha chain (IL-15Ralpha)
      has been suggested as the main mechanism for IL-15 anchoring to the cell surface,
      but it is also evident that IL-15 can exist as a transmembrane protein. We herein
      demonstrate that replacement of the first 41 residues of human IL-15 (hIL-15)
      with Igkappa chain leader sequence resulted in secretion of most of the
      recombinant hIL-15 expressed in transfectant cells, thus identifying the
      transmembrane region of IL-15. A fusion protein (hIL-15Ralpha-Fc) between the
      extracellular domain of hIL-15Ralpha and the Fc fragment of IgG1 was prepared and
      shown to be able to bind with transmembrane IL-15 (tmIL-15). The level of tmIL-15
      expression in macrophages, activated T cells and B cells from 6-month-old BXSB
      male mice, an animal model for systemic lupus erythematosus (SLE), was
      significantly increased compared with that from BXSB females or young males. In
      addition, hIL-15Ralpha-Fc was able to block the T cell stimulating and anti
      apoptotic effect of the tmIL-15-positive BXSB macrophages in vitro. Intravenous
      administration of hIL-15Ralpha-Fc reduced the titre of autoantibodies against
      dsDNA and also proteinuria in aged BXSB males, implying that neutralization of IL
      15 activity in vivo may be an effective way of treating SLE.

PMID- 19170965
TI  - Contribution of intestinal epithelial cells to innate immunity of the human gut-
      studies on polarized monolayers of colon carcinoma cells.
AB  - The aim was to establish an in vitro model for studies of innate defence
      mechanisms of human intestinal epithelium. Ultrastructural characterization and
      determination of mRNA expression levels for apical glycocalyx and mucous
      components showed that polarized, tight monolayers of the colon carcinoma cell
      lines T84 and Caco2 acquire the features of mature- and immature columnar
      epithelial cells, respectively. Polarized monolayers were challenged with non
      pathogenic Gram+ and Gram- bacteria from the apical side and the proinflammatory
      cytokines interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha)
      and interleukin-1beta (IL-1beta) from the basolateral side. Immune responses were
      estimated as changes in mRNA expression levels for the mucous component mucin-2
      (MUC2), the glycocalyx components carcinoembryonic antigen (CEA), CEA-related
      cell adhesion molecule-1 (CEACAM1), CEACAM6, CEACAM7 and MUC3, the antimicrobial
      factors human beta-defensin-1 (hBD1), hBD2, hBD3 and lysozyme, the chemokine IL-8
      and the cytokines IL-6 and TNF-alpha. Tight monolayer cells were generally
      unresponsive to bacterial challenge, but increased their hBD2 levels when
      challenged with Bacillus megaterium. T84 cells also increased their TNF-alpha
      levels upon bacterial challenge. Tight monolayer cells responded to cytokine
      challenge suggesting awareness of basolateral attack. TNF-alpha induced
      significantly increased levels of IL-8 and TNF-alpha itself in both cell lines
      suggesting recruitment and activation of immune cells in the underlying mucosa in
      vivo. Cytokine challenge also increased levels of CEACAM1, which includes two
      functionally different forms, CEACAM1-L and CEACAM1-S. In T84 cells, IFN-gamma
      was selective for CEACAM1-L while TNF-alpha upregulated both forms. Increased
      CEACAM1 expression may influence epithelial function and communication between
      epithelial cells and intraepithelial lymphocytes.

PMID- 19170966
TI  - Molecular characterization of patients with X-linked Hyper-IgM syndrome:
      description of two novel CD40L mutations.
AB  - Type 1, X-linked Hyper-IgM syndrome (HIGM1) is caused by mutations in the gene
      encoding the CD154 protein, also known as CD40 ligand (CD40LG). CD40L is
      expressed in activated T cells and interacts with CD40 receptor expressed on B
      lymphocytes and dendritic cells. Affected patients present cellular and humoral
      immune defects, with infections by intracellular, opportunistic and extracellular
      pathogens. In the present study we investigated the molecular defects underlying
      disease in four patients with HIGM1. We identified four distinct CD40L mutations,
      two of them which have not been previously described. P1 harboured the novel
      p.G227X mutation which abolished CD40L expression. P2 had a previously described
      frame shift deletion in exon 2 (p.I53fsX65) which also prevented protein
      expression. P3 demonstrated the previously known p.V126D change in exon 4,
      affecting the TNF homology (TNFH) domain. Finally, P4 evidenced the novel p.F229L
      mutation also located in the TNFH domain. In silico analysis of F229L predicted
      the change to be pathological, affecting the many hydrophobic interactions of
      this residue. Precise molecular diagnosis in HIGM syndrome allows reliable
      detection of carriers, making genetic counselling and prenatal diagnosis
      possible.

PMID- 19170967
TI  - Activity of alpha2,6-sialyltransferase and its gene expression in peripheral B
      lymphocytes in patients with IgA nephropathy.
AB  - It is known that aberrant sialylation of IgA1 is involved in the pathogenesis of
      IgA nephropathy (IgAN). We hypothesize that aberrant sialylation of serum IgA1
      may result from changes in the activity of alpha2,6-sialyltransferase (alpha2,6
      ST) or expression of its coding gene ST6GALNAC2 in peripheral B lymphocytes.
      Sixty patients with IgAN and 20 healthy controls were enrolled. Peripheral B
      lymphocytes were isolated by CD-19-positive magnetic beads. The expression level
      of ST6GALNAC2 was quantitatively analysed by real-time reverse-transcriptase
      polymerase chain reaction (PCR). Serum IgA1 and sialylation levels were detected
      by enzyme-linked immunosorbent assay (ELISA) and specific lectin-binding ELISA.
      Activity of alpha2,6-ST was measured by specific lectin-binding ELISA. Expression
      of ST6GALNAC2 in B peripheral lymphocytes was significantly lower in patients
      with IgAN than that in normal controls (3.7 +/- 2.2 versus 6.3 +/- 2.3, P =
      0.016); alpha2,6-ST activity in B lymphocytes was correlated positively with the
      level of alpha2,6-sialic acid in serum IgA1 in patients (n = 42) and controls (n
      = 12) (r = 0.37, P = 0.007). However, alpha2,6-ST activity did not differ between
      patients with IgAN and controls (1.19 +/- 1.43 versus 1.06 +/- 1.17, P > 0.05).
      These data suggested that reduced sialylation of serum IgA1 may result from
      decreased expression of ST6GALNAC2. The factors affecting activity of alpha2,6-ST
      in the sialylation of IgA1 need to be further investigated.

PMID- 19170968
TI  - The efficacy of teaching psychology students exposure and response prevention for
      obsessive-compulsive disorder.
AB  - The aim of the study was to investigate whether inexperienced student therapists
      could successfully learn exposure and response prevention for obsessive
      compulsive disorder. Twenty out of 21 outpatients completed treatment as
      delivered by ten psychology students. A total of 60 hours group supervision and
      approximately 30 hours with individual supervision was given to the students over
      the course of three semesters. Large effect sizes were observed for measures of
      symptoms and depression. Sixty-two percent (N= 13) of the intent to treat group
      achieved clinical significant change and 81% no longer met the diagnosis criteria
      (N= 17). The treatment effects observed at the 6 month follow-up period were
      promising. The results are encouraging for training students in evidence based
      treatment for specific disorders.

PMID- 19170969
TI  - Career maturity: a latent means and covariance structure analysis of Daidalos.
AB  - A latent means and covariance structure analysis was conducted to assess the
      construct validity and construct comparability in the measuring of career
      maturity across boys and girls. The career maturity inventory has been coined
      Daidalos. The sample consisted of 2,443 high school students recruited from one
      county in Norway. Of these, 1,132 were males, and 1,311 were females. The mean
      age of the participants was 17 years of age. Goodness-of-fit statistics provided
      support for a five-factor first-order model in which the factor loadings, factor
      covariances and item intercepts were invariant across groups. Additionally,
      deltaS-B chi2 was shown to be non-significant for the testing of invariance of
      the measurement model. Three significant differences in latent means were
      detected, with boys scoring higher on negative attitudes toward school or dropout
      intentions, and girls scoring higher on career uncertainty and need for world-of
      work information.

PMID- 19170970
TI  - The Women's Health Questionnaire (WHQ): a psychometric evaluation of the 36-item
      Norwegian version.
AB  - The Women's Health Questionnaire (WHQ) was designed specifically to study
      possible changes that occur during menopause. The purpose of this study was to
      perform a psychometric evaluation of the Norwegian version of the WHQ by
      examining the factor structure and construct validity of the instrument. Data
      used for the evaluation were collected at baseline of the ACUFLASH study, a
      randomized, controlled clinical trial that evaluated the effect of acupuncture
      treatment on menopausal symptoms. Altogether, 267 women with a very high
      frequency of hot flushes were included in the study. Some deficiencies in the WHQ
      questionnaire were observed when applied to this sample, including an unclear
      factor structure, low alpha values for some dimensions, and a strong floor effect
      in the vasomotor symptoms dimension. The total scale score appears reliable, but
      care should be taken when interpreting some of the subscales.

PMID- 19170971
TI  - Parent training for young Norwegian children with ODD and CD problems: predictors
      and mediators of treatment outcome.
AB  - Participants were 121 children, aged 4-8 years referred for conduct problems, and
      their mothers. A parent training intervention was implemented in two outpatient
      clinics in Norway. Treatment responders were defined as children scoring below a
      cut-off on the Eyberg Child Behavior Inventory, a score below an optimal cut-off
      for children in day-care and school as reported by teachers, in addition to a 30%
      reduction or greater in observed negative parenting. Self-reported parenting
      practices were explored as potential mediators. The results of logistic
      regression analyses showed that high levels of maternal stress, clinical levels
      of ADHD, and being a girl predicted a poorer outcome in conduct problems at home,
      while pretreatment clinical levels of ADHD predicted a poorer outcome as
      perceived by the teachers. Harsh and inconsistent parental disciplining emerged
      as significant partial mediators of changes in conduct problems, highlighting the
      importance of altering parenting practices to modify young children's conduct
      problems.

PMID- 19170972
TI  - Are you sitting comfortably? The political economy of the body.
AB  - The aim of this paper is to examine the relationship between the mass production
      of furniture in modern industrial societies and lower back pain (LBP). The latter
      has proven to be a major cost to health services and private industry throughout
      the industrialised world and now represents a global health issue as recent WHO
      reports on obesity and LBP reveal. Thus far there have been few co-ordinated
      attempts to deal with the causes of the problem through public policy. Drawing
      upon a range of sources in anthropology, health studies, politics and economics,
      the paper argues that this a modern social problem rooted in the contingent
      conjuncture of natural and social causal mechanisms. The key question it raises
      is: what are the appropriate mechanisms for addressing this problem? This paper
      develops an analysis rooted in libertarian social theory and argues that both the
      state and the capitalist market are flawed mechanisms for resolving this problem.
      There remains a fundamental dilemma for libertarians, however. Whilst the state
      and the market may well be flawed mechanisms, they are the dominant ones shaping
      global political economy. To what extent can libertarians work within these
      structures and remain committed to libertarian goals?

PMID- 19170973
TI  - Time, self and the medication day: a closer look at the everyday work of
      'adherence'.
AB  - This article examines the everyday work of participating in pharmaceutical
      treatment for HIV infection in the context of urgent calls for adherence. Drawing
      on interviews and focus-group conversations with people taking antiretroviral
      drugs, the analysis explicates the work that goes into striving for adherence.
      What comes into view is a form of time work that brings about a temporary
      alignment between the inner experience of time, standard clock time, and the
      requirements of the medication schedule. Time work is largely cognitive; the
      pills, however, must actually be swallowed to complete the dose, occasioning, for
      some people, additional work to suppress or refashion emotional responses of
      anger and resistance. Both the time work and the emotional work of taking
      antiretroviral drugs draw people into forms of self work, including self
      examination and self-adjustment, as they develop strategies for 'doing
      adherence'.

PMID- 19170980
TI  - Correlation of 4Pi and electron microscopy to study transport through single
      Golgi stacks in living cells with super resolution.
AB  - Two problems have hampered the use of light microscopy for structural studies of
      cellular organelles for a long time: the limited resolution and the difficulty of
      obtaining true structural boundaries from complex intensity curves. The advent of
      modern high-resolution light microscopy techniques and their combination with
      objective image segmentation now provide us with the means to bridge the gap
      between light and electronmicroscopy in cell biology applications. In this study,
      we provide the first comparative correlative analysis of three-dimensional
      structures obtained by 4Pi microscopy and segmented by a zero-crossing procedure
      with those of transmission electron microscopy (TEM). The distribution within the
      cisternae of isolated Golgi stacks of the cargo protein procollagen 3 was mapped
      by both 4Pi microscopy and TEM for a detailed comparative analysis of their
      imaging capabilities. A high correlation was seen for the structures, indicating
      the particular accuracy of the 4Pi microscopy. Furthermore, for the first time,
      transport of a cargo molecule (vesicular stomatitis virus G protein-pEGFP)
      through individual Golgi stacks (labeled by galactosyl transferase-venus-YFP) was
      visualized by 4Pi microscopy. Following the procedures validated by the
      correlative analysis, our transport experiments show that (i) VSVG-pEGFP rapidly
      enter/exit individual Golgi stacks, (ii) VSVG-pEGFP never fills the GalT-venusYFP
      compartments completely and (iii) the GalT-venusYFP compartment volume increases
      upon VSVG-pEGFP arrival. This morphological evidence supports some previous TEM
      based observations of intra-Golgi transport of VSVG-pEGFP and provides new
      insights toward a better understanding of protein progression across Golgi
      stacks. Our study thus demonstrates the general applicability of super resolution
      fluorescence microscopy, coupled with the zero-crossing segmentation procedure,
      for structural studies of suborganelle protein distributions under living cell
      conditions.

PMID- 19170981
TI  - Differential membrane association properties and regulation of class I and class
      II Arfs.
AB  - ADP-ribosylation factor (Arf) proteins are small guanosine triphosphatases
      (GTPases) that act as major regulators of intracellular vesicular trafficking and
      secretory organelle pathway integrity. Like all small monomeric GTPases, Arf
      proteins cycle between a GDP-bound and a GTP-bound state, and this cycling is
      catalysed by guanine nucleotide exchange factors (GEFs) and GTPase-activating
      proteins. While the class I Arfs, especially Arf1, have been studied extensively,
      little is known as yet about the function and regulation of class II Arfs, Arf4
      and Arf5. In this study, we show that Arf proteins show class-specific dynamic
      behaviour. Moreover, unlike class I Arfs, membrane association of class II Arfs
      is resistant to inhibition of large Arf GEFs by Brefeldin A. Through the
      construction of Arf chimeric proteins, evidence is provided that the N-terminal
      amphipathic helix and a class-specific residue in the conserved interswitch
      domain determine the membrane-binding properties of class I and class II Arf
      proteins. Our results show that fundamental differences exist in behaviour and
      regulation of these small GTPases.

PMID- 19170982
TI  - Sensing, signaling and sorting events in kidney epithelial cell physiology.
AB  - The kidney regulates body fluid, ion and acid/base homeostasis through the
      interaction of a host of channels, transporters and pumps within specific tubule
      segments, specific cell types and specific plasma membrane domains. Furthermore,
      renal epithelial cells have adapted to function in an often unique and
      challenging environment that includes high medullary osmolality, acidic pHs,
      variable blood flow and constantly changing apical and basolateral 'bathing'
      solutions. In this review, we focus on selected protein trafficking events by
      which kidney epithelial cells regulate body fluid, ion and acid-base homeostasis
      in response to changes in physiological conditions. We discuss aquaporin 2 and G
      protein-coupled receptors in fluid and ion balance, the vacuolar H(+)-adenosine
      triphosphatase (V-ATPase) and intercalated cells in acid/base regulation and
      acidification events in the proximal tubule degradation pathway. Finally, in view
      of its direct role in vesicle trafficking that we outline in this study, we
      propose that the V-ATPase itself should, under some circumstances, be considered
      a fourth category of vesicle 'coat' protein (COP), alongside clathrin, caveolin
      and COPs.

PMID- 19170983
TI  - The JAL antigen (RH48) is the result of a change in RHCE that encodes Arg114Trp.
AB  - BACKGROUND: The JAL antigen (Rh48) was discovered more than 30 years ago when it
      caused hemolytic disease of the fetus and newborn in an African American family.
      A decade later it was found to cause hemolytic disease of the fetus and newborn
      in a Caucasian family. The presence of the same low-prevalence antigen in two
      different ethnic groups is rare, but additional JAL+ in both groups was
      subsequently identified. This study was undertaken to investigate the RH gene(s)
      responsible for expression of JAL and to determine the structural relationship
      between JAL and other Rh antigens. STUDY DESIGN AND METHODS: Samples from 17 JAL+
      people were included: 2 Caucasian, 6 African American, 7 African Brazilian, 1
      Caribbean, and 1 Puerto Rican. RHCE and RHD were investigated at the genomic
      level, and Rh cDNAs were cloned and sequenced for some samples. RESULTS:
      Caucasian JAL+ probands had RHCE*Ce, while JAL+ probands with African ancestry
      had RHCE*ce, but all had a nucleotide 340C>T change in Exon 3 of RHCE predicted
      to encode Arg114Trp. The JAL-encoding RHCE*ce also had 733C>G (Leu245Val) and was
      linked to conventional RHD or to RHD*DAU0. CONCLUSIONS: JAL+ results from a
      nucleotide 340C>T (Arg114Trp) on either a Ce or ce background. Homology modeling
      of the JAL+ RhCE protein suggests that the Arg-->Trp change eliminates a critical
      loop-stabilizing H-bond between the side chain of Arg114 and the e-specific amino
      acid Ala226. Additionally, accommodation of the bulky tryptophan would disrupt
      the conformation of the extracellular loops containing C/c- and e-specific amino
      acids, providing a structural hypothesis for the simultaneous altered expression
      of C/c, e, and V/VS antigens.

PMID- 19170984
TI  - Identification of an optimal concentration of platelet gel for promoting
      angiogenesis in human endothelial cells.
AB  - BACKGROUND: Numerous studies have supported the use of topical blood components
      to improve wound healing and tissue regeneration. Platelet gel (PG), a
      hemocomponent obtained from mix of activated platelets (PLTs) and
      cryoprecipitate, is currently being used clinically in an attempt to improve
      tissue healing. The present study sought to define the most effective PG
      concentration to promote angiogenesis in vitro. STUDY DESIGN AND METHODS: The
      effects of PG-released supernatant at different concentrations on human
      endothelial cells were studied using different in vitro assays (proliferation,
      migration, invasion, cord formation, and wound healing). RESULTS: The
      concentration of PG-released supernatant had a significant influence on the
      angiogenic potential of endothelial cells. The optimal concentration for the
      stimulation of angiogenesis was 1.5 x 10(6) PLTs per microL in most of the in
      vitro experiments used in this study. Lower or higher concentrations of PG
      displayed a lower angiogenic potential. CONCLUSION: An optimal concentration of
      PG to promote angiogenesis in human endothelial cells was identified. Excessively
      high PG concentrations may inhibit the angiogenic process, thereby being
      counterproductive for wound healing in a clinical setting.

PMID- 19170985
TI  - Production Assistance for Cellular Therapies (PACT): four-year experience from
      the United States National Heart, Lung, and Blood Institute (NHLBI) contract
      research program in cell and tissue therapies.
AB  - BACKGROUND: In 2002, the US National Heart, Lung, and Blood Institute (NHLBI)
      conducted a workshop to determine needs of the cell therapy community. A
      consensus emerged that improved access to cGMP facilities, regulatory assistance,
      and training would foster the advancement of cellular therapy. STUDY DESIGN AND
      METHODS: A 2003 NHLBI request for proposals resulted in four contracts being
      awarded to three cell-manufacturing facilities (Baylor College of Medicine,
      University of Minnesota, and University of Pittsburgh) and one administrative
      center (The EMMES Corporation). As a result, Production Assistance for Cellular
      Therapies (PACT) was formed. RESULTS: As of October 1, 2008, PACT has received 65
      preliminary applications of which 45 have been approved for product manufacture.
      A variety of cell therapies are represented including T-regulatory cells, natural
      killer cells, adipose-derived stem cells, cardiac progenitor cells for cardiac
      disease, hematopoietic progenitor cells (HPCs) for central nervous system
      applications, cytotoxic T lymphocytes, and dendritic cells. A total of 169
      products have been administered under 12 applications and 2 reagents were
      manufactured and delivered. Fourteen peer-reviewed publications and 15 abstracts
      have resulted from the PACT project to date. A cell therapy textbook is nearly
      complete. PACT technical projects have addressed assay development, rapid
      endotoxin testing, shipping of cell products, and CD34+ HPC isolation from low
      volume marrow. Educational Web seminars and on-site training through workshops
      have been conducted. CONCLUSIONS: PACT is an active and successful cell therapy
      manufacturing resource in the United States, addressing research and training
      while forging relationships among academia, industry, and participating
      institutions.

PMID- 19170986
TI  - Blood platelet production: a novel approach for practical optimization.
AB  - BACKGROUND: The challenge of production and inventory management for blood
      platelets (PLTs) is the requirement to meet highly uncertain demands. Shortages
      are to be minimized, if not to be avoided at all. Overproduction, in turn, leads
      to high levels of outdating as PLTs have a limited "shelf life." Outdating is to
      be minimized for ethical and cost reasons. STUDY DESIGN AND METHODS: Operations
      research (OR) methodology was applied to the PLT inventory management problem.
      The problem can be formulated in a general mathematical form. To solve this
      problem, a five-step procedure was used. This procedure is based on a combination
      of two techniques, a mathematical technique called stochastic dynamic programming
      (SDP) and computer simulation. RESULTS: The approach identified an optimal
      production policy, leading to the computation of a simple and nearly optimal PLT
      production "order-up-to" rule. This rule prescribes a fixed order-up-to level for
      each day of the week. The approach was applied to a test study with actual data
      for a regional Dutch blood bank. The main finding in the test study was that
      outdating could be reduced from 15-20 percent to less than 0.1 percent with
      virtually no shortages. Blood group preferences and extending the shelf life of
      more than 5 days appeared to be of marginal effect. CONCLUSION: In this article
      the worlds of blood management and the mathematical discipline of OR are brought
      together for the optimization of blood PLT production. This leads to simple
      nearly optimal blood PLT production policies that are suitable for practical
      implementation.

PMID- 19170987
TI  - Lack of evidence of transfusion transmission of Creutzfeldt-Jakob disease in a US
      surveillance study.
AB  - BACKGROUND: Since 2004, several reported transfusion transmissions of variant
      Creutzfeldt-Jakob disease (vCJD) in the United Kingdom have reawakened concerns
      about the possible risk of similar transmissions of nonvariant or classic forms
      of CJD. STUDY DESIGN AND METHODS: Patients with a CJD diagnosis and a history of
      donating blood were reported to the study coordinator. Through review of blood
      distribution and hospital records, the recipients of blood components from these
      donors were identified. We then determined each recipient's vital status and, if
      deceased, the cause(s) of death identified by matching the recipient's personal
      identifiers with the Centers for Disease Control and Prevention's National Death
      Index database. We conducted such searches after recipients were enrolled in this
      study and annually thereafter for those who remained alive. RESULTS: The study
      included a total of 36 blood donors who subsequently developed CJD and 436
      recipients. Through 2006, 91 of these recipients were still alive, 329 were
      deceased, and 16 were lost to follow-up. After transfusion, these three groups
      had survived a total of 2096.0 person-years. A total of 144 recipients survived 5
      years or longer after transfusion and 68 of them had received blood donated 60 or
      fewer months before the onset of CJD in the donor. We identified no recipient
      with CJD. CONCLUSIONS: The current results of this large, ongoing lookback study
      show no evidence of transfusion transmission of CJD. They reinforce the
      conclusion that the risk, if any, of transfusion transmission of prion disease by
      CJD donors is significantly lower than the comparable risk of such transmission
      by vCJD donors.

PMID- 19170988
TI  - The impact of discontinuation of 7-day storage of apheresis platelets (PASSPORT)
      on recipient safety: an illustration of the need for proper risk assessments.
AB  - BACKGROUND: Seven-day stored apheresis platelets (APs) were withdrawn from the US
      market after detection of two culture-positive units from 2571 tested at outdate
      in the PASSPORT surveillance study. The impact of this discontinuation on
      recipient safety was explored using mathematical modeling. STUDY DESIGN AND
      METHODS: Risk models for septic transfusion reactions (STRs) and transfusion
      related acute lung injury (TRALI) were developed. Key assumptions were 400,000
      annual APs transfused, equivalent STR risk for platelets (PLTs) stored for 5 days
      or more and zero for PLTs stored for less than 5 days, whole blood-derived PLTs
      (WBplts) administered in 5-unit pools, a 4.6-fold higher risk of false-negatives
      with surrogate versus culture-based bacterial testing, an AP TRALI risk between 1
      per 1000 and 1 per 10,000, and a delay in TRALI risk reduction implementation in
      some centers by 6 to 12 months due to limited PLT availability. RESULTS: STR risk
      could increase, decrease, or remain the same depending on the percentage of
      inventory replaced by surrogate-tested WBplts versus culture-tested apheresis or
      whole blood PLTs. A delay in TRALI risk reduction implementation is likely to
      result in a comparable or greater risk during the delayed implementation period
      than the safety achieved with regard to STRs, even in the most favorable case
      scenario. CONCLUSION: A comprehensive risk assessment should have been conducted
      before the decision to discontinue PASSPORT. Risk assessments using accepted
      methods (and actual data when available) should precede any major blood safety
      decisions.

PMID- 19170989
TI  - Thrombin generation and clot formation in methylene blue-treated plasma and
      cryoprecipitate.
AB  - BACKGROUND: Methylene blue (MB) treatment of plasma is known to reduce the
      activity of clotting factors, but its effect on thrombin generation and clot
      formation is not well documented. STUDY DESIGN AND METHODS: Individual clotting
      factors and inhibitors and global tests of thrombin generation and clot formation
      using rotational thrombelastometry (ROTEM) were assessed in a paired study of
      standard or MB plasma and cryoprecipitate (n = 20 each). RESULTS: MB treatment
      resulted in a 10 percent reduction in endogenous thrombin potential and 30
      percent decrease in peak thrombin as well as the expected 20 to 35 percent loss
      of Factor (F)VIII, fibrinogen, and FXI activity. MB treatment had no effect on
      the rate of clot formation and increased the clot firmness by 20 percent as
      assessed by ROTEM. There were minimal further changes in either coagulation
      factor levels or thrombin generation when thawed plasma was stored for an
      additional 24 hours. FVIII and fibrinogen content of MB cryoprecipitate was
      reduced by 30 and 40 percent, respectively, but this was not associated with
      altered clot time or rate of clot formation by ROTEM and only an 8 percent
      decrease in clot firmness. CONCLUSIONS: It is concluded that MB treatment is
      associated with a reduction in the thrombin-generating capacity of plasma, but
      has very little effect on the strength of clot formation as assessed by
      thrombelastometry. The thrombin-generating capacity of standard and MB plasma is
      relatively unaltered by subsequent storage of thawed plasma at 4 degrees C for 24
      hours.

PMID- 19170990
TI  - Social support attenuates presyncopal reactions to blood donation.
AB  - BACKGROUND: The experience of unpleasant blood donation reactions (e.g.,
      dizziness, nausea, and fainting) has been linked to negative attitudes about
      donation and decreased likelihood of repeat donation. Consequently, interventions
      to reduce the adverse effects of blood donation are important and likely to
      increase donor retention. Based on laboratory studies suggesting that social
      support attenuates both physical and psychological responses to stress, the
      present study hypothesized that the presence of a supportive person during the
      donation process may help reduce reactions. STUDY DESIGN AND METHODS: A final
      sample of 65 men and women with fewer than three prior donations was randomly
      assigned to either donate blood as usual or donate with a supportive research
      assistant. Donors in the support condition were accompanied throughout the
      donation process by a female research assistant who provided encouragement, made
      reassuring remarks, and engaged in small talk. Donors in both conditions
      completed a series of questions to assess anxiety, experience of prefaint
      reactions, and willingness to provide a future donation. RESULTS: Compared to
      standard donation controls, donors in the social support condition reported fewer
      prefaint reactions (F(1,61) = 9.15, p = 0.004, eta(2)= 0.13) and greater
      likelihood of donating again within the next year (Z =-1.70, p < 0.05, one
      tailed). CONCLUSION: Relatively novice donors report reduced reactions to blood
      donation when accompanied by a supportive individual, suggesting that social
      support may be a simple strategy to enhance the donation experience and possibly
      increase donor retention.

PMID- 19170991
TI  - Deferred donor care in a regional hospital blood center in Ghana.
AB  - BACKGROUND: In sub-Saharan Africa, the viral marker burden in blood donor
      populations ranges between 10 and 30 percent. Deferred donors constitute a rare
      population of asymptomatic human immunodeficiency virus (HIV)- and hepatitis B
      virus (HBV)-infected individuals with high likelihood of long survival if cared
      for. Deferred donor care provides an opportunity for a public health impact on
      highly pathogenic infections. STUDY DESIGN AND METHODS: Between 2004 and 2007,
      all candidate donors deferred before donation for reactivity of anti-HIV,
      hepatitis C virus antibody (anti-HCV), and hepatitis B virus surface antigen
      (HBsAg) rapid tests were informed and referred to a donor care program consisting
      of test confirmation, information, counseling, and potential referral for follow
      up and therapy. Dedicated trained nurses supervised the program including alanine
      aminotransferase (ALT) level testing to identify liver disease. RESULTS: In a 4
      year period 51,100 donors were screened and 5778, 1578, and 227 candidate donors
      were deferred for reactivity to HBV, HIV, or HCV serologic markers, respectively.
      The rates of entry into the donor care program were 48, 14.3, and 22 percent of
      deferred donors, respectively. A total of 83 of 210 HBsAg-positive donors with
      elevated ALT levels were referred and 66 received antiviral treatment. A total of
      89 of 516 confirmed anti-HIV-positive donors were referred to the hospital
      acquired immune deficiency syndrome clinic for follow-up. CONCLUSIONS: With
      little additional expense, the deferred donor care program identified
      asymptomatic infections with high odds of benefiting from monitoring and therapy.
      In the local circumstances, this public health-limited but definite impact was
      permitted by the rapid-test pre-donation screening, and this impact could be
      increased if more resources were available.

PMID- 19170992
TI  - Blood donors with positive direct antiglobulin tests are at increased risk for
      cancer.
AB  - BACKGROUND: Positive direct antiglobulin tests (DATs) have been associated with
      both autoimmunity and lymphoproliferative disorders. However, it is unknown
      whether DAT+ in healthy blood donors is associated with an increased risk of
      malignancies. STUDY DESIGN AND METHODS: In the current study, all blood donors
      with DAT+ samples were identified during the years 1999 through 2003 through the
      Magen David Adom National Blood Services in Israel. This study compared the risk
      of cancer among 586 DAT+ and 2344 DAT- donors who were matched according to sex,
      age, and year of donation. The risk of cancer in DAT+ donors was also compared to
      expected rates in the general Israeli population. Cancer was ascertained through
      the Israel Cancer Registry. RESULTS: Malignancies occurred among 17 (2.9%) of the
      DAT+ and 27 (1.2%) of the DAT- blood donors; of these, 3 donors in the DAT+ group
      were diagnosed with hematopoietic malignancies within 12 months of their
      donation. Even after excluding these early cases, the relative risk of developing
      cancer was 2.14 (95% confidence interval [CI], 1.13-4.10) comparing DAT+ with DAT
      donors, while the relative risk for hematopoietic cancer was 8.3 (95% CI, 1.5
      43.2). Comparing DAT+ blood donors with the general population, the standardized
      incidence ratios (observed/expected cases) were elevated at 2.11 (95% CI, 1.15
      3.54; p = 0.16) for all malignancies and 8.03 (95% CI, 2.2-20.6; p = 0.003) for
      hematologic malignancies. CONCLUSION: There is evidence of a significantly
      increased risk of cancer, especially hematologic malignancies, among blood donors
      with a positive DAT even within a short follow-up period.

PMID- 19170993
TI  - Detection of blood group genes using multiplex SNaPshot method.
AB  - BACKGROUND: The determination of blood group antigens in patients and donors is
      of primary importance in transfusion medicine. Blood group antigens are inherited
      and are polymorphic in nature. The majority of polymorphic blood group antigens
      arise from single-nucleotide polymorphisms (SNPs) in the blood group genes. Many
      DNA-based assays, such as species-specific polymerase chain reaction (PCR), PCR
      restriction fragment length polymorphism, and microchips, have been described to
      study variant blood group genes. In this study, the SNaPshot (Applied Biosystems)
      method was adapted to detect SNPs in 10 common blood group systems. STUDY DESIGN
      AND METHODS: DNA regions of interest were amplified in multiplex PCR and annealed
      to specific oligonucleotide probe primers of different lengths. AmpliTaq DNA
      polymerase extended the primers by adding only a single fluorescent ddNTP to its
      3' end and was detected by differential mobility in capillary electrophoresis in
      a genetic analyzer. Results were analyzed using computer software in SNaPshot
      default analysis method. RESULTS: Seventeen SNP sites in 29 blood samples,
      previously phenotyped and/or genotyped, were used to test the accuracy and
      reproducibility of multiplex SNaPshot assays. The results were compared with the
      previously analyzed types. SNaPshot analyses predicted the 17 SNP sites
      accurately for all the 29 blood samples. Both homozygous and heterozygous blood
      groups were detected with equal confidence. CONCLUSION: Blood group detection by
      SNaPshot method is a practical alternative to antibody-dependent phenotype
      prediction. Starting with DNA, this method is fast with a turnaround time of 24
      hours with mean reagent cost around $2 per SNP detected.

PMID- 19170994
TI  - Reduction of disulfide bonds within anti-D results in enhanced Fcgamma receptor
      blockade.
AB  - BACKGROUND: We have investigated whether chemicals known to disrupt disulfide
      bonds are capable of altering immunoglobulin anti-D structure resulting in an
      increased efficacy of the chemically modified anti-D to inhibit Fcgamma receptor
      (FcgammaR)-mediated phagocytosis. If successful, this would provide a rationale
      to explore this mechanism of enhancing FcgammaR blockade for future use in
      immunoglobulin therapies for immune cytopenias. STUDY DESIGN AND METHODS: Anti-D
      that was shown to block 50 percent of the FcgammaR-mediated phagocytosis of
      opsonized red blood cells (RBCs) using a monocyte monolayer assay (MMA) was
      combined with two different thiol-containing compounds, dithiothreitol (DTT) or p
      toluenesulfonylmethyl mercaptan, with or without treatment with iodoacetamide,
      and allowed to react. Excess chemical was removed by extensive dialysis. FcgammaR
      blockade was assessed by MMA with dialyzed, untreated, or chemically treated anti
      D using both D+ and D- opsonized target RBCs. Toxicity was determined by
      fluorescence-activated cell sorting. Aggregates and oligomerization of chemically
      treated anti-D were examined using gel filtration-high pressure liquid
      chromatography. RESULTS: Using disulfide-reducing compounds to chemically modify
      anti-D significantly increases the efficacy of the anti-D to induce an FcgammaR
      blockade and decrease phagocytosis in vitro of opsonized D+ or D- RBCs. This
      effect was shown not due to unbound residual chemical, toxicity, or formation of
      immunoglobulin G oligomers. S-alkylation was required when using low
      concentrations of reducing compound. CONCLUSION: Our results demonstrate that
      irreversible reduction of interchain disulfide bonds within the immunoglobulin
      anti-D results in a significantly increased efficacy to inhibit FcgammaR-mediated
      phagocytosis regardless of opsonized target cell. With the use of this strategy,
      more effective and less expensive immunoglobulin treatment for immune cytopenias
      such as immune thrombocytopenic purpura or autoimmune hemolytic anemia may be
      developed.

PMID- 19170995
TI  - Identification of RHD alleles with the potential of anti-D immunization among
      seemingly D- blood donors in Upper Austria.
AB  - BACKGROUND: Aberrant RHD alleles leading to a reduced expression of D antigen on
      the red blood cell (RBC) surface may be mistyped as D- by serology. To quantify
      the occurrence of weak D, DEL, and D+/- chimera among apparent D- first-time
      blood donors, polymerase chain reaction (PCR) screening was implemented as a
      routine service. STUDY DESIGN AND METHODS: A total of 23,330 pretyped D- samples
      were tested for RHD markers in Exons 4, 7, and 10 in pools of 20 by PCR. Samples
      with positive results in PCR were reevaluated by exon-specific PCRs, DNA
      sequencing, and serologic methods. RESULTS: Among 94 PCR-positive samples, 74
      exhibited a weak D or DEL phenotype, dubbed weak D type 1, weak D type 2, weak D
      type 5, weak D type 32, weak D type 4.3, RHD(M295I), RHD(del147), and
      RHD(1227G>A). The most prevalent alleles were weak D type 4.3 (n = 31) and
      RHD(IVS3+1G>A) (n = 24). CONCLUSIONS: As a clinical consequence, 74 blood donor
      samples carrying weak D and DEL phenotypes with the potential of causing
      secondary immunizations in recipients were reclassified as D+. Those samples were
      reliably amplified by RHD Exon 7 PCR; therefore, its usage in the Upper Austrian
      population is recommended. The association of the weak D type 4.3 samples with a
      ce leads to the policy that all apparently D- donors should be tested with
      genotyping methods; otherwise, potentially immunogenic RHD alleles may be
      overseen.

PMID- 19170996
TI  - An autoanti-Kp b immunoglobulin M that simulates antigen suppression.
AB  - BACKGROUND: Patients may present with an antibody against a blood group antigen,
      a negative direct antiglobulin test (DAT), and a null phenotype. Typically, this
      represents an alloantibody in a null individual. However, on occasion, the
      antibody disappears coincident with conversion to a positive red blood cell (RBC)
      phenotype. This has been called antigen loss, antigen suppression, or weakened
      antigenicity. Herein, a unique serologic profile that mimics this pattern, when
      in fact antigen loss did not occur, is described. STUDY DESIGN AND METHODS: RBCs
      and serum were analyzed using a gel microtyping system and flow cytometry.
      Genomic DNA was amplified by polymerase chain reaction and sequenced. RESULTS:
      Initially, an anti-Kp(b) was detected in MTS gel, RBCs typed K-k-Kp(b-), and the
      DAT was negative for immunoglobulin G (IgG). Later, the anti-Kp(b) disappeared
      and RBCs phenotyped as K-k+Kp(b+). Analysis of initial specimens by flow
      cytometry identified an immunoglobulin M (IgM) anti-Kp(b) with a positive IgM
      specific DAT; eluates contained an anti-Kp(b) at immediate spin. Supporting the
      presence of the Kell glycoprotein, RBCs agglutinated with anti-Js(b). Sequencing
      showed homozygosity for Kp(b) with no mutations surrounding the Kp(b)
      polymorphism. CONCLUSION: In antigen loss, antibody masking is excluded by a
      negative DAT. However, because typical DAT reagent does not detect IgM, such
      reasoning was inaccurate in the current case. In addition, an anti-Kp(b) resulted
      in RBCs typing k-, even though no anti-k was detected. Overall, this case
      suggests that an IgM may mask adjacent epitopes and illustrates the potential to
      mistake a non-IgG autoantibody as antigen loss.

PMID- 19170997
TI  - From mad cows to sensible blood transfusion: the risk of prion transmission by
      labile blood components in the United Kingdom and in France.
AB  - Transfusion transmission of the prion, the agent of variant Creutzfeldt-Jakob
      disease (vCJD), is now established. Subjects infected through food may transmit
      the disease through blood donations. The two nations most affected to date by
      this threat are the United Kingdom (UK) and France. The first transfusion cases
      have been observed in the UK over the past 5 years. In France, a few individuals
      who developed vCJD had a history of blood donation, leading to a risk of
      transmission to recipients, some of whom could be incubating the disease. In the
      absence of a large-scale screening test, it is impossible to establish the
      prevalence of infection in the blood donor population and transfused patients.
      This lack of a test also prevents specific screening of blood donations. Thus,
      prevention of transfusion transmission essentially relies at present on deferral
      of "at-risk" individuals. Because prions are present in both white blood cells
      and plasma, leukoreduction is probably insufficient to totally eliminate the
      transfusion risk. In the absence of a screening test for blood donations,
      recently developed prion-specific filters could be a solution. Furthermore, while
      the dietary spread of vCJD seems efficiently controlled, uncertainty remains as
      to the extent of the spread of prions through blood transfusion and other
      secondary routes.

PMID- 19170999
TI  - Current value of serologic test for syphilis as a surrogate marker for blood
      borne viral infections among blood donors in the United States.
AB  - BACKGROUND: Serologic screening for syphilis has been justified in part as a
      surrogate marker for infections caused by other pathogens such as human
      immunodeficiency virus (HIV). This study assessed the current surrogate value of
      the test. STUDY DESIGN AND METHODS: Testing results for blood donors with the
      American Red Cross Blood Services between January 1, 2006, and December 31, 2007,
      were analyzed. All donations were tested according to standard procedures for
      markers of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), human T
      lymphotropic virus (HTLV), syphilis, and other infections. The frequency of
      window-period (w-p) infections interdicted by syphilis testing was estimated.
      RESULTS: There were significantly higher frequencies of HIV, HCV, hepatitis B
      surface antigen (HBsAg), and HTLV confirmed-positive donations among those with
      positive syphilis test results, although the sensitivity of syphilis test
      positivity in these groups was low. Among more than 3 million repeat donors with
      complete testing through reactive donation confirmation for both syphilis and HIV
      (anti-HIV and HIV RNA), 225 seroconverted for syphilis but not for anti-HIV or
      HIV RNA and 83 converted for HIV (anti-HIV or HIV RNA) but not for syphilis, with
      only 1 who converted for both syphilis and HIV, resulting in an incidence ratio
      of 150 (95% confidence interval, 21-1080) and a sensitivity of 1.2 percent. No
      syphilis seroconverters converted for HCV, HBsAg, or anti-HTLV. CONCLUSION:
      Syphilis testing presents no surrogate value for incident HCV, HBV, and HTLV
      infections and could only remove approximately 1 HIV w-p unit of every 148
      million donations.

PMID- 19170998
TI  - Impact of ABO mismatching on the outcomes of allogeneic related and unrelated
      blood and marrow stem cell transplantations for hematologic malignancies: IPD
      based meta-analysis of cohort studies.
AB  - BACKGROUND: The impact of donor-recipient ABO matching on outcomes after
      allogeneic stem cell transplantation has been a matter of controversy. STUDY
      DESIGN AND METHODS: Individual patient data-based meta-analysis was conducted
      with a pooled data set provided through six published and one unpublished
      cohorts. Outcomes in recipients of peripheral blood or bone marrow
      transplantation for hematologic malignancies were evaluated. A multivariate Cox
      model was used to adjust differences in outcomes of patients receiving ABO
      matched grafts with those receiving major, minor, or bidirectional mismatched
      grafts. Considering multiple testing, p values of less than 0.05 and 0.001 were
      considered significant for the primary and secondary endpoints, respectively.
      RESULTS: In all, 1208 cases, including 697 ABO-matched and 202 major, 228 minor,
      and 81 bidirectional mismatched transplants, were analyzed. Overall, adverse
      impact of ABO matching on overall survival (OS), as a primary endpoint, was not
      observed (adjusted hazard ratios [95% confidence intervals]: major, 1.03 [0.82
      1.30], p = 0.81; minor, 1.19 [0.97-1.47], p = 0.10; bidirectional, 1.25 [0.91
      1.72], p = 0.17). Among related stem cell recipients, ABO matching had no
      significant influence on OS, while the minor and bidirectional mismatched groups
      among unrelated stem cell recipients exhibited lower OS with marginal
      significance, especially in patients with acute leukemia, patients who received
      transplants after 1998, and patients who underwent transplants at Asian centers.
      CONCLUSIONS: Our meta-analysis demonstrates no adverse association between any
      ABO mismatching and survival. However, marginally lower OS found in recipients of
      minor or bidirectional mismatched grafts from unrelated donors suggested the need
      for larger studies focusing on unrelated transplants.

PMID- 19171000
TI  - Evidence of acute primary occult hepatitis B virus infection in an Italian repeat
      blood donor.
AB  - BACKGROUND: Preliminary evidence of cases of acute occult hepatitis B virus (HBV)
      infection (OBI) has been recently reported in the literature. Furthermore, OBI
      definition has been the object of an international consensus conference. STUDY
      DESIGN AND METHODS: A case of acute primary OBI was identified and followed up in
      a repeat female blood donor using a highly sensitive nucleic acid test (NAT;
      Procleix Ultrio on Tigris, Chiron). Genotyping and sequencing of virus isolates
      from donor and contact cases were performed. RESULTS: The blood donor never
      developed detectable hepatitis B surface antigen (HBsAg) until seroconversion to
      antibody to hepatitis B surface antigen/antibody to hepatitis B core antigen. A
      very low viral load was observed during the infection course (<50 IU/mL). Donor
      HBV DNA sequencing consistently showed a CCA deletion leading to amino acid T116
      deletion in the small envelope protein (S). Other sequence features showed high
      homology between donor and contact case, suggesting a sexual transmission.
      DISCUSSION: The main explanation for HBsAg undetectability relies on the very low
      level of viremia observed. The single-amino-acid deletion found in the S protein
      cannot account for HBsAg detection failure, because the capture antibody of the
      assay used is targeted to a different sequence epitope (aa121-124). Meanwhile,
      CCA deletion may have impacted the virus replication efficiency since it affects
      the overlapping reverse transcriptase "finger" domain of the polymerase gene.
      These findings define this case as an acute primary OBI, confirming the existence
      of this condition. NAT with high sensitivity is the only screening enabling
      prevention of HBV transmission by transfusion in such cases.

PMID- 19171001
TI  - Evaluation of in vitro storage properties of prestorage pooled whole blood
      derived platelets suspended in 100 percent plasma and treated with amotosalen and
      long-wavelength ultraviolet light.
AB  - BACKGROUND: Amotosalen, a psoralen, has been utilized for photochemical treatment
      (PCT) of apheresis platelets (PLTs) and pooled buffy coat PLTs suspended in
      additive solution. In the United States, the source of many PLT transfusions is
      from whole blood-derived PLTs prepared by the PLT-rich plasma (PRP) method. This
      study investigated the in vitro PLT properties of amotosalen-PCT of leukoreduced
      pools of PLTs prepared by the PRP method and suspended in 100 percent plasma.
      STUDY DESIGN AND METHODS: On Day 1 of storage, 12 leukoreduced (n = 6) or 10
      leukoreplete (n = 6) ABO-identical PLT concentrates were pooled, separated into
      two pools of 6 or 5 units, respectively, and leukoreduced (leukoreplete pools
      only). Each pool of 5 or 6 units was then photochemically treated (designated
      "test": amotosalen plus 3.0 J/cm(2) long-wavelength ultraviolet light followed by
      amotosalen/photoproduct removal) while the remaining identical pool (designated
      "control") was untreated. PLT in vitro assays were performed on test and control
      pools during 7-day storage. RESULTS: PCT resulted in slightly reduced pH in test
      pools compared to that of matched control pools after 5 days of storage (5-unit
      pools: test, 6.96 +/- 0.12 vs. control, 7.15 +/- 0.09, p = 0.0033; 6-unit pools:
      test, 6.90 +/- 0.10 vs. control, 7.07 +/- 0.09, p < 0.0001). Test pools
      adequately maintained many other in vitro properties including PLT morphology,
      hypotonic shock response, and extent of shape change parameters during 5-day
      storage, which, like pH, also differed from those of controls. The pH of test and
      control pools declined on Day 7, with 1 of 6 test pools (either 5 or 6 units)
      having a pH value of less than 6.20, while all control pools had pH values of
      more than 6.66. CONCLUSION: PCT of leukoreduced PLT pools of whole blood-derived
      PLTs in 100 percent plasma maintained adequate PLT in vitro variables through 5
      days of storage.

PMID- 19171003
TI  - Reassessment of deferrals for tattooing and piercing.
AB  - BACKGROUND: In August 2005, the Canadian Blood Services decreased the deferral
      period for tattooing and ear or body piercing from 12 to 6 months. This study
      assessed the impact of this change on blood safety and availability. STUDY DESIGN
      AND METHODS: The prevalence of these activities was assessed on an anonymous mail
      out survey of 40,000 recent donors. Transmissible disease (TD) marker rates were
      calculated using the National Epidemiology Donor Database. A case-control study
      was performed comparing risk factors in TD-positive donors with matched controls.
      Donor deferral rates were assessed before and after the change in deferral
      period. RESULTS: The prevalence rates of tattoo, ear piercing, and body piercing
      were 13.7, 53.6, and 10.4 percent in survey respondents, respectively, with up to
      0.7 percent of activity likely to represent deferrable risk. TD marker rate was
      low and stable at 21.6 per 100,000 donations before and 19.2 per 100,000
      donations after the change in deferral length. Remote tattoo was associated with
      hepatitis C virus (HCV) risk (odds ratio, 5.43; 95% confidence interval, 1.82
      16.2), but neither recent tattoo nor piercing was a risk factor for HCV or
      hepatitis B virus. Shortening of the deferral period reduced deferrals by 20
      percent for tattoo and 32 percent for piercing. CONCLUSION: There was no
      measurable adverse effect on safety and a positive but less than expected effect
      on blood availability after shortening the deferral period for tattoo and
      piercing. The length of other temporary deferrals should be reassessed, since
      their current contribution to blood safety may be negligible.

PMID- 19171002
TI  - Anaerobic storage of red blood cells in a novel additive solution improves in
      vivo recovery.
AB  - BACKGROUND: In preliminary studies, anaerobic red blood cell (RBC) storage
      reduced oxidative damage and phosphatidylserine exposure while maintaining
      adenosine triphosphate levels. The purpose of this study was to compare the 24
      hour recovery and life span of autologous RBCs stored 6 and 9 weeks using OFAS3
      additive solution in an anaerobic environment, compared to control RBCs
      aerobically stored in AS-3 for 6 weeks. STUDY DESIGN AND METHODS: Eight subjects
      were entered into a randomized, crossover study. Whole blood was collected from
      each subject twice separated by 12 weeks or more into CP2D and leukoreduced.
      Controls were stored in AS-3. Test units in OFAS3 were oxygen depleted with argon
      then stored 9 weeks in an anaerobic chamber at 1 to 6 degrees C. At the end of
      each storage period, RBCs were labeled with (51)Cr and (99m)Tc and reinfused to
      the subject following standard methods to determine double-label recovery and
      life span. Hypotheses tests were conducted using paired, repeated-measures
      analysis of variance. RESULTS: Recovery for the anaerobically stored test RBC was
      significantly better than control at 6 weeks (p = 0.023). Test units at 9 weeks
      were not different than the 6-week control units (p = 0.73). Other in vitro
      measures of RBC characteristics followed the same trend. Two test units at 9
      weeks had hemolysis of greater than 1 percent. CONCLUSION: Anaerobically stored
      RBCs in OFAS3 have superior recovery at 6 weeks compared to the controls and
      equivalent recovery at 9 weeks with no change in life span. Anaerobic storage of
      RBCs may provide improved RBCs for transfusion at 6 weeks of storage and may
      enable extending storage beyond the current 42-day limit.

PMID- 19171004
TI  - Autologous platelet concentrates for bone graft enhancement in sinus lift
      procedure.
AB  - BACKGROUND: Autologous platelet (PLT)-rich plasma has been reported in some
      studies to promote osteogenesis. The goal of this study was to demonstrate that
      osteogenesis gained by mixing autologous PLT concentrates (APCs) with a small
      quantity of autologous bone graft could give a sufficient quality to lead to
      dental implant placement. The second goal was to compare this osteogenesis with
      that obtained by a traditional method (iliac bone graft), through clinical,
      radiologic, and histologic methods. STUDY DESIGN AND METHODS: Eighteen patients
      needing bilateral sinus floor augmentation were enrolled. One sinus was grafted
      with iliac crest bone alone, and the other sinus with a small quantity of bone
      and APC. Panoramic view, computed tomography scan, and biopsies were performed 6
      months after the initial surgery to compare ossification. RESULTS: The adjunction
      of APCs permitted a 60 percent reduction of bone graft required for sinus floor
      elevation. The bone obtained with APCs had the same histologic and mechanical
      characteristics as the bone obtained by traditional graft. CONCLUSION: Topical
      use of APCs might be helpful in bone reconstruction. No clinical, radiologic, or
      histologic osteogenesis inhibition of high PLT concentration was observed. The
      resulting osteogenesis was adapted to dental implant placements.

PMID- 19171005
TI  - Anemia screening in potential female blood donors: comparison of two different
      quantitative methods.
AB  - BACKGROUND: Anemia screening before blood donation requires an accurate, quick,
      practical, and easy method with minimal discomfort for the donors. The aim of
      this study was to compare the accuracy of two quantitative methods of anemia
      screening: the HemoCue 201(+) (Aktiebolaget Leo Diagnostics) hemoglobin (Hb) and
      microhematocrit (micro-Hct) tests. STUDY DESIGN AND METHODS: Two blood samples of
      a single fingerstick were obtained from 969 unselected potential female donors to
      determine the Hb by HemoCue 201(+) and micro-Hct using HemataSTAT II (Separation
      Technology, Inc.), in alternating order. From each participant, a venous blood
      sample was drawn and run in an automatic hematology analyzer (ABX Pentra 60, ABX
      Diagnostics). Considering results of ABX Pentra 60 as true values, the
      sensitivity and specificity of HemoCue 201(+) and micro-Hct as screening methods
      were compared, using a venous Hb level of 12.0 g per dL as cutoff for anemia.
      RESULTS: The sensitivities of the HemoCue 201(+) and HemataSTAT II in detecting
      anemia were 56 percent (95% confidence interval [CI], 46.1%-65.5%) and 39.5
      percent (95% CI, 30.2%-49.3%), respectively (p < 0.001). Analyzing only
      candidates with a venous Hb level lower than 11.0 g per dL, the deferral rate was
      100 percent by HemoCue 201(+) and 77 percent by HemataSTAT II. The specificities
      of the methods were 93.5 and 93.2 percent, respectively. CONCLUSION: The HemoCue
      201(+) showed greater discriminating power for detecting anemia in prospective
      blood donors than the micro-Hct method. Both presented equivalent deferral error
      rates of nonanemic potential donors. Compared to the micro-Hct, HemoCue 201(+)
      reduces the risk of anemic female donors giving blood, specially for those with
      lower Hb levels, without increasing the deferral of nonanemic potential donors.

PMID- 19171006
TI  - A cost-effectiveness analysis of continuous subcutaneous insulin injection versus
      multiple daily injections in type 1 diabetes patients: a third-party US payer
      perspective.
AB  - OBJECTIVE: To estimate the long-term cost-effectiveness of using continuous
      subcutaneous insulin infusion (CSII) compared with multiple daily injections
      (MDI) of insulin in adult and child/young adult type 1 diabetes mellitus (T1DM)
      patients from a third-party payer perspective in the United States. METHOD: A
      previously validated health economic model was used to determine the incremental
      cost-effectiveness ratio (ICER) of CSII compared with MDI using published
      clinical and cost data. The primary input variable was change in HbA(1c), and was
      assumed to be an improvement of -0.9% to -1.2% for CSII compared with MDI for
      child/young adult and adults, respectively. A series of Markov constructs
      simulated the progression of diabetes-related complications. RESULTS: CSII was
      associated with an improvement in quality-adjusted life-years (QALYs) gained of
      1.061 versus MDI for adults and 0.799 versus MDI for children/young adults. ICERs
      were $16,992 and $27,195 per QALY gained for CSII versus MDI in adults and
      children/young adults, respectively. Improved glycemic control from CSII led to a
      lower incidence of diabetes complications, with the most significant reduction in
      proliferative diabetic retinopathy (PDR), end stage renal disease (ESRD), and
      peripheral vascular disease (PVD). The number needed to treat (NNT) for PDR was
      nine patients, suggesting that only nine patients need to be treated with CSII to
      avoid one case of PDR. The NNT for ESRD and PVD was 19 and 41, respectively.
      CONCLUSIONS: Setting the willingness to pay at $50,000/QALY, the analysis
      demonstrated that CSII is a cost-effective option for patients with T1DM in the
      United States.

PMID- 19171007
TI  - Management of childhood urinary tract infections: an economic modeling study.
AB  - Childhood urinary tract infections (UTIs) can lead to renal scarring and
      ultimately to terminal renal failure, which has a high impact on quality of life,
      survival, and health-care costs. Variation in the treatment of UTIs between
      practices is high. OBJECTIVE: To assess the cost-effectiveness of a maximum care
      model for UTIs in children, implying more testing and antibiotic treatment,
      compared with current practice in primary care in The Netherlands. METHODS: We
      performed a probabilistic modeling study using Markov models. Figures used in the
      model were derived from a systematic review of the research literature.
      Multidimensional Monte Carlo simulation was used for the probabilistic analyses.
      RESULTS: Maximum care gained 0.00102 (males) and 0.00219 (girls) QALYs (quality
      adjusted life-years) and saved 42.70 euro (boys) and 77.81 euro (girls) in 30
      years compared with current care, and was thus dominant. Net monetary benefit of
      maximum care ranged from 20 euro to 200 euro for a willingness to pay for a QALY
      ranging from 0 euro to 80,000 euro, respectively. Maximum care was also dominant
      over improved current care, although less dominant than to current care.
      CONCLUSIONS: This study suggested that maximum care for childhood UTI was
      dominant in the long run to current care, meaning that it delivered more quality
      of life at lower costs. Nevertheless, making firm conclusions is not possible,
      given the limitations of the input data.

PMID- 19171008
TI  - Immune response to measles vaccine in 6 month old infants in Papua New Guinea.
AB  - OBJECTIVE: To assess the efficacy of the current measles immunization schedule in
      Papua New Guinea, which is to give the first dose at 6 months of age and the
      second at 9 months. METHODS: Humoral immune response study of 140 Papua New
      Guinean infants at 6 months of age, measuring measles IgG antibodies by enzyme
      immunoassay before and 85 days after the 6-month dose of measles vaccine.
      RESULTS: After vaccination at 6 months, 35.7% of infants developed a level of
      measles antibodies consistent with protection (IgG >330 IU/ml); 17.7% had an
      antibody response (150-330 IU/ml) that is likely to afford some protection; 46.8%
      had no detectable antibody response (IgG <150 IU/ml). Among 53 infants with no
      antibody response, 37 (69.5%) developed an antibody response, while 42.4% (37/87)
      of those with maternal antibodies sero-converted (P = 0.002). CONCLUSIONS:
      Antibody response to measles vaccine was lower than expected at 6 months. While
      the presence of maternally derived antibodies accounted for some of the limited
      seroconversion in young infants, other factors are involved. Issues to be
      considered in determining the value of the first dose of measles vaccination in
      mid infancy in poor countries are complex and antibody responses are only one
      factor. Others, such as cell mediated immune responses, the non-specific
      protective effect of measles vaccine in preventing illness and death and the
      practicalities of uptake of vaccines at different ages, are also important.

PMID- 19171009
TI  - Individual efficacy of intermittent preventive treatment with sulfadoxine
      pyrimethamine in primi- and secundigravidae in rural Burkina Faso: impact on
      parasitaemia, anaemia and birth weight.
AB  - OBJECTIVE: To assess the efficacy at individual level of intermittent preventive
      treatment with sulfadoxine-pyrimethamine (IPTp-SP) in primi- and secundigravidae
      in rural Burkina Faso. METHODS: Data of 1441 women enrolled in a health centre
      randomized trial and delivering a live-singleton between September 2004 and
      October 2006 were analysed at individual level. Prevalence of peripheral and
      placental parasitaemia, anaemia (PCV <33%), low-birth weight (<2500 g; LBW), mean
      packed cell volume (PCV) and birth weight were compared in relation to the number
      of directly observed SP doses. RESULTS: Two or more doses of SP significantly
      reduced the risk of placental parasitaemia [adjusted odds ratio (AOR) = 0.04,
      95%CI = 0.003-0.60, P = 0.023] and anaemia at delivery (AOR = 0.31, 95%CI = 0.18
      0.52, P < 0.001). IPTp was associated with reduced risk of LBW in primigravidae
      (AOR = 0.11, 95%CI = 0.07-0.17, P < 0.001) but not secundigravidae (AOR = 0.70,
      95%CI = 0.26-1.91, P = 0.452). For each increment in number of SP doses mean PCV
      increased by 1.0% (95%CI = 0.4-1.7, P = 0.005) at 32 weeks gestation, by 1.2%
      (95%CI = 0.2-2.2, P = 0.025) at delivery and mean birth weight by 220 g (95%CI =
      134-306 P < 0.001) in primigravidae and by 102 g (95%CI = 55-148, P = 0.001) in
      secundigravidae. CONCLUSION: The risk of malaria infection was significantly
      reduced by IPTp with SP in primi- and secundigravidae in rural Burkina Faso. The
      impact on clinical outcomes is lower and mainly limited to primigravidae for LBW.
      Incomplete uptake of IPTp-SP and limited effect in low risk groups together may
      substantially dilute the measurable impact of effective interventions. This needs
      to be taken into account when evaluating interventions at community level.

PMID- 19171010
TI  - Echinococcosis, toxocarosis and toxoplasmosis screening in a rural community in
      eastern Kazakhstan.
AB  - OBJECTIVE: To determine the extent of carnivore-transmitted parasitic zoonoses in
      a community in eastern Kazakhstan, a region where cystic echinococcosis (CE) re
      emerged in recent years. METHODS: Cross sectional ultrasound study of 3126 human
      subjects to determine the extent of human cystic and alveolar echinococcosis
      (AE). Blood samples were taken from each subject and analysed for antibodies
      against Echinococcus, Toxocara and Toxoplasma spp. Each subject was questioned
      about possible risk factors that might be associated with zoonotic transmission.
      Analysis employed a mixed modelling approach based on the results of the
      ultrasound study, the serological results and the results of the questionnaire.
      Bayesian techniques were employed to estimate diagnostic performance. A
      helminthological study of the local dog population was also undertaken. RESULTS:
      A total of 23 subjects tested positive for CE on ultrasound and a further three
      individuals had strong serological evidence of infection. Another 24 reported
      treatment for CE. Ultrasound lesions or treatment for CE were associated with
      poverty. No ultrasound evidence of AE was found, but one individual had strong
      serological evidence of exposure to Echinococcus multilocularis. Toxoplasma
      seropositivity (16%; 504 individuals) increased with age. Household level
      Toxoplasma-seropositivity was associated with unsafe drinking water. Toxocara
      seropositivity (11%; 349 individuals) was more frequent in children and in
      individuals who disposed of dog faeces on the vegetable garden. A purgation study
      of dogs indicated that 13% of dogs in the community were infected with
      Echinococcus granulosus, 5% with E. multilocularis and 2% with Toxocara canis
      respectively. CONCLUSIONS: There is significant transmission of E. granulosus to
      humans in this community. Transmission may be associated with poverty. There is
      little evidence of E. multilocularis transmission to humans, despite the presence
      in the parasite in the domestic dog population. Toxoplasma is actively
      transmitted and there is evidence for transmission by the water supply. Children
      are at highest risk of exposure to Toxocara.

PMID- 19171011
TI  - The HIV-exposed, uninfected African child.
AB  - The increasing success of prevention of mother-to-child HIV transmission
      programmes means that in Africa, very large numbers of HIV-exposed, uninfected
      (HIV-EU) children are being born. Any health problems that these children may
      have will thus be of enormous public health importance, but to date have been
      largely neglected. There is some evidence that HIV-EU African children are at
      increased risk of mortality, morbidity and slower early growth than their HIV
      unexposed counterparts. A likely major cause of this impaired health is less
      exposure to breast milk as mothers are either less able to breastfeed or stop
      breastfeeding early to protect their infant from HIV infection. Other
      contributing factors are parental illness or death resulting in reduced care of
      the children, increased exposure to other infections and possibly exposure to
      antiretroviral drugs. A broad approach for psychosocial support of HIV-affected
      families is needed to improve health of HIV-EU children. High quality
      programmatic research is needed to determine how to deliver such care.

PMID- 19171012
TI  - Preventive measures in infancy to reduce under-five mortality: a case-control
      study in The Gambia.
AB  - OBJECTIVE: To investigate the relationship between child mortality and common
      preventive interventions: vaccination, trained birthing attendants, tetanus
      toxoid during pregnancy, breastfeeding and vitamin A supplementation. METHODS:
      Case-control study in a population under demographic surveillance. Cases (n =
      141) were children under five who died. Each was age and sex-matched to five
      controls (n = 705). Information was gathered by interviewing primary caregivers.
      RESULTS: All but one of the interventions - whether the mother had received
      tetanus toxoid during pregnancy - were protective against child mortality after
      multivariate analysis. Having a trained person assisting at child birth (OR 0.2
      95% CI 0.1-0.4), receiving all vaccinations by 9 months of age (OR 0.1; 95% CI
      0.01-0.3), being breastfed for more than 12 months (Children breastfed between 13
      and 24 months OR 0.1 95% CI 0.03-0.3, more than 25 months OR 0.1 95% CI 0.01-0.5)
      and receiving vitamin A supplementation at or after 6 months of age (OR 0.05; 95%
      CI 0.01-0.2) were protective against child death. CONCLUSIONS: This study
      confirms the value of at least four available interventions in the prevention of
      under-five death in The Gambia. It is now important to identify those who are not
      receiving them and why, and to intervene to improve coverage across the
      population.

PMID- 19171013
TI  - Disability adjusted life years lost to dengue in Brazil.
AB  - OBJECTIVES: To assess the dengue burden in Brazil, and to compare it over three
      spatial scales: in the city of Rio de Janeiro, the state of Rio de Janeiro, and
      in Brazil overall. METHODS: We calculated disability adjusted life years (DALYs)
      lost to dengue per million individuals annually from 1986 through 2006. To
      calculate DALYs, we compiled data on the number of dengue cases by age, clinical
      syndrome and outcome. We evaluated the sensitivity of our results to
      multiplication factors used to adjust for inaccuracies in reporting using a Monte
      Carlo method. RESULTS: From 1986 through 2006, a mean of 56, 47 and 22 DALYs per
      million individuals annually were lost to dengue in the city of Rio de Janeiro,
      in the state of Rio de Janeiro and in Brazil, respectively. Over 80% of the
      dengue burden derived from dengue fever cases. The dengue burden was highest at
      the city-level with a maximum single-year estimate of 560 DALYs per million
      individuals for 2002. CONCLUSIONS: Assessment of dengue burden requires
      consideration of all clinical syndromes over multiple years. Our results indicate
      that the dengue burden is as high as the burden of other major infectious
      diseases that afflict the Brazilian population, including malaria. These results
      may prompt policy makers to elevate the prioritization of dengue control, and
      allocate resources needed to curtail the increasing dengue burden.

PMID- 19171014
TI  - Use of destained cytology slides for the application of routine special stains.
AB  - BACKGROUND: Special stains to demonstrate microorganisms or intra- and
      extracellular substances have not been evaluated in detail regarding their
      applicability and usefulness in destained cytologic specimens. OBJECTIVES: The
      aim of this study is to compare the results of routine special stains on
      destained slides previously stained with Hemacolor and on fresh (unstained)
      specimens. METHODS: Archival Hemacolor-stained fine needle aspirate specimens of
      inflammation with infectious agents (bacterial, mycobacterial, and fungal
      infections), neoplasia (melanoma, myxosarcoma, and mammary adenocarcinoma), and
      hemorrhage (pericardial effusion) from 14 dogs and 7 cats were selected. Cells in
      a minimum of 4 fields were photographed and 5 slides from each case were then
      destained by different methods (alcohol acid or microwave). Seven special stains
      were applied selectively to the destained slides, depending on the cytologic
      findings: periodic acid Schiff, Grocott-Gomori methenamine silver, Gram's, Ziehl
      Neelsen, Alcian blue, Fontana-Masson, and Prussian blue. The same fields were
      rephotographed and 2 observers evaluated the slides qualitatively, with
      comparison to fresh cytologic specimens from similar lesions. RESULTS: Special
      stains applied to destained slides demonstrated the expected cellular and
      extracellular material or organisms independent of the destaining method.
      Staining intensity, nonspecific staining (background), cell morphology, and
      nuclear counterstaining results were similar to those of special stains applied
      to fresh unstained slides. CONCLUSIONS: Destaining does not appear to affect the
      results of routine special staining for cytologic specimens. Destaining before
      special stains may be a valuable diagnostic strategy when few slides are present
      or only stained slides are available.

PMID- 19171015
TI  - Disseminated histiocytic sarcoma with peripheral blood involvement in a Bernese
      Mountain dog.
AB  - A 6-year-old Bernese Mountain dog was presented with a history of lethargy and
      weight loss of 2 weeks duration. On physical examination the dog had pale mucous
      membranes and tachypnea. Ultrasound examination revealed hepatomegaly,
      splenomegaly, and mesenteric lymphadenomegaly. Results of a CBC included marked
      normocytic normochromic nonregenerative anemia, marked thrombocytopenia, and
      moderate leukocytosis with mild neutrophilia and a large population of
      unclassified round cells (6.2 x 10(3)/microL). The unclassified cells
      occasionally were bi- or multinucleated and had variably abundant pale basophilic
      cytoplasm that contained multiple irregular clear vacuoles and occasionally
      erythrocytes. Fine needle aspirate specimens of the mesenteric lymph nodes and
      spleen were composed of a population of round pleomorphic cells with the same
      features as the circulating cells. On flow cytometric analysis of peripheral
      blood, the unclassified cells expressed CD18, CD45, CD11c, CD1c, and CD14;
      immunocytochemical analysis of blood smears also indicated the cells were
      positive for CD1c, CD1a, and CD11c. The dog died a few hours after referral. The
      histologic interpretation of samples collected from spleen, liver, and lymph
      nodes was malignant neoplasia of histiocytic origin. Immunohistochemical staining
      yielded negative results for CD11d, a marker of red-pulp macrophages, ruling out
      hemophagocytic histiocytic sarcoma. Based on clinical and pathologic findings,
      the final diagnosis was disseminated histiocytic sarcoma (DHS) with peripheral
      blood involvement. To our knowledge, DHS in a dog with evidence and
      immunophenotyping of neoplastic cells in peripheral blood has been reported only
      rarely.

PMID- 19171016
TI  - What is your diagnosis? Rectal scraping from a dog with diarrhea.
AB  - A 3-year-old, spayed female, mixed-breed dog was evaluated for chronic diarrhea,
      vomiting, and weight loss. A marked inflammatory leukogram, mild regenerative
      anemia, and marked hypoalbuminemia were noted. Cytologic evaluation of a rectal
      scraping revealed numerous round to ovoid protozoal cysts, 5-25 microm in
      diameter, with small to moderate amounts of pale blue cytoplasm and round
      eosinophilic nuclei. A distinct, variably sized, round to oval vacuole was often
      seen within the cytoplasm and frequently displaced the nucleus. The cysts were
      morphologically similar to Blastocystis sp., an amoeba-like protozoal parasite
      found in both diseased and asymptomatic humans and animals. Histologic findings
      in endoscopic biopsies from the stomach, duodenum, ileum, and colon were
      unremarkable and protozoal organisms were not observed. The dog was diagnosed
      with exocrine pancreatic insufficiency based on markedly decreased serum levels
      of trypsin-like immunoreactivity. Alteration of gastrointestinal flora secondary
      to the underlying pancreatic disease likely allowed overgrowth of the protozoa,
      which were considered an incidental finding. Their identification was important
      in avoiding an incorrect diagnosis and unwarranted treatment.

PMID- 19171017
TI  - B-cell lymphoma with Mott cell differentiation in two young adult dogs.
AB  - Two young adult dogs with gastrointestinal signs were each found to have an intra
      abdominal mass based on physical examination and diagnostic imaging. On
      exploratory laparotomy, small intestinal masses and mesenteric lymphadenopathy
      were found in both dogs; a liver mass was also found in dog 1. Cytologic and
      histologic examination of intestinal and liver masses and mesenteric lymph nodes
      revealed 2 distinct lymphoid cell populations: lymphoblasts and atypical Mott
      cells. With Romanowsky stains, the atypical Mott cells contained many discrete,
      clear to pale blue cytoplasmic inclusions consistent with Russell bodies that
      were positive by immunohistochemistry for IgM and CD79a in both dogs and for IgG
      in dog 2. The Mott cells and occasional lymphoblasts stained strongly positive
      with periodic acid-Schiff. Using flow cytometric immunophenotyping in dog 1, 60%
      of peripheral blood mononuclear cells and 85% of cells in an affected lymph node
      were positive for CD21, CD79a, IgM, and MCH II, indicative of B-cells. With
      electron microscopy, disorganized and dilated endoplasmic reticulum was seen in
      Mott cells in tumors from both dogs. Antigen receptor gene rearrangement analysis
      of lymph node and intestinal masses indicated a clonal B-cell population. Based
      on cell morphology, tissue involvement, and evidence for clonal B-cell
      proliferation, we diagnosed neoplasms involving Mott cells. To the authors'
      knowledge, this is the second report of Mott cell tumors or, more appropriately,
      B-cell lymphoma with Mott cell differentiation, in dogs. More complete
      characterization of this neoplasm requires further investigation of additional
      cases. This lymphoproliferative disease should be considered as a differential
      diagnosis for canine gastrointestinal tumors.

PMID- 19171018
TI  - Presumptive increase in protein-bound serum calcium in a dog with multiple
      myeloma.
AB  - An 11-year-old male castrated Australian Shepherd was presented with a history of
      lethargy, panting, and weight loss for 1 month. Physical examination revealed a
      moderately enlarged spleen. Laboratory abnormalities included thrombocytopenia
      and marked hypercalcemia, with hyperglobulinemia, hypoalbuminemia, and a
      monoclonal spike in the beta-globulin region on serum protein electrophoresis.
      Serum total calcium concentration was markedly increased (16.5 mg/dL, reference
      interval 8.9-11.4 mg/dL) but ionized calcium concentration (1.39 mmol/L) was
      within the reference interval (1.25-1.45 mmol/L). Isosthenuria was noted, but the
      dog was not polyuric or polydipsic. Serum parathyroid hormone concentration was
      within reference limits and parathyroid hormone-related peptide concentration was
      0 pmol/L. Radiographic findings were largely unremarkable. Results of cytologic
      evaluation of a fine-needle aspirate specimen from the spleen indicated plasma
      cell neoplasia. Based on the results of the electrophoresis, splenic aspirates,
      radiographs, and hypercalcemia, a diagnosis of splenic multiple myeloma was made.
      The marked hypercalcemia, normal ionized calcium and parathyroid hormone
      concentrations, and lack of osteolytic lesions indicated a presumptive increase
      in protein-bound serum calcium, likely due to binding to molecules of the
      paraprotein (M protein). Protein binding of calcium in dogs with multiple myeloma
      should be considered as a potential mechanism of elevated total serum calcium
      concentration.

PMID- 19171019
TI  - Serum protein concentrations from clinically healthy horses determined by agarose
      gel electrophoresis.
AB  - BACKGROUND: Serum protein electrophoresis is a useful screening test in equine
      laboratory medicine. The method can provide valuable information about changes in
      the concentrations of albumin and alpha-, beta-, and gamma-globulins and thereby
      help characterize dysproteinemias in equine patients. Reference values for horses
      using agarose gel as a support medium have not been reported. OBJECTIVES: The
      purpose of this study was to establish reference intervals for serum protein
      concentrations in adult horses using agarose gel electrophoresis and to assess
      differences between warm-blooded and heavy draught horses. In addition, the
      precision of electrophoresis for determining fraction percentages and the
      detection limit were determined. METHODS: Blood samples were obtained from 126
      clinically healthy horses, including 105 Thoroughbreds and 21 heavy draught
      horses of both sexes and ranging from 2 to 20 years of age. The total protein
      concentration was determined by an automated biuret method. Serum protein
      electrophoresis was performed using a semi-automated agarose gel electrophoresis
      system. Coefficients of variation (CVs) were calculated for within-run and within
      assay precision. Data from warm-blooded and draught horses were compared using
      the Mann-Whitney U test. RESULTS: Within-run and within-assay CVs were <5% for
      all protein fractions. No significant difference was found between warm-blooded
      and heavy draught horses and so combined reference intervals (2.5-97.5%) were
      calculated for total protein (51.0-72.0 g/L), albumin (29.6-38.5 g/L), alpha(1)
      globulin (1.9-3.1 g/L), alpha(2)-globulin (5.3-8.7 g/L), beta(1)-globulin (2.8
      7.3g/L), beta(2)-globulin (2.2-6.0 g/L), and gamma-globulin (5.8-12.7 g/L)
      concentrations, and albumin/globulin ratio (0.93-1.65). CONCLUSION: Using agarose
      gel as the supporting matrix for serum protein electrophoresis in horses resulted
      in excellent resolution and accurate results that facilitated standardization
      into 6 protein fractions.

PMID- 19171020
TI  - Hematologic abnormalities and flow cytometric immunophenotyping results in dogs
      with hematopoietic neoplasia: 210 cases (2002-2006).
AB  - BACKGROUND: Growing interest in veterinary oncohematology has facilitated the
      recent development and advancement of new techniques, such as flow cytometry, for
      immunophenotyping hematopoietic neoplasia in animals. OBJECTIVE: The aim of this
      retrospective study was to characterize hematologic abnormalities and flow
      cytometric immunophenotyping (FCI) results in cases of hematopoietic neoplasia in
      dogs. METHODS: Signalment, CBC data, and FCI results were obtained for 210 dogs
      with blood samples submitted to our laboratory. Immunophenotyping was carried out
      using an Epics XL-MCL flow cytometer and a panel of 10 antibodies (CD45, CD3,
      CD4, CD8, CD79, CD21, CD14, CD34, CD41/61, CD61). The prevalence and severity of
      hematologic abnormalities was determined for the different types of hematopoietic
      neoplasms. RESULTS: Based on cell morphology and phenotype, cases were classified
      as: acute lymphoblastic leukemia (ALL, n=51), acute myeloid leukemia (AML, n=33),
      chronic lymphocytic leukemia (CLL, n=61), and leukemic high-grade lymphoma (L
      HGL, n=65). Most cases of ALL (47/51) and L-HGL (41/65) had a B-cell phenotype,
      while most cases of CLL (54/61) had a T-cell phenotype, with a high prevalence of
      the large granular lymphocyte subtype (49/61). Anemia was found in 85% of all
      cases and was significantly more severe in ALL and AML compared with CLL and L
      HGL. Neutropenia was seen in 64-78% of acute leukemias (AML and ALL) in contrast
      to no cases of CLL and 11% of L-HGL. Thrombocytopenia was seen in 88-90% of acute
      leukemias in contrast to 15% of CLL and 40% of L-HGL. Thrombocytopenia was more
      prevalent (71% vs 22%) and significantly more severe in T-cell vs B-cell L-HGL.
      CONCLUSION: A standard CBC is useful in suggesting the type of hemoproliferative
      disorder and may also help to predict the phenotype, especially in cases of L
      HGL.

PMID- 19171021
TI  - Further validation of a pruritus severity scale for use in dogs.
AB  - A scale to assess the severity of pruritus in dogs was further validated.
      Comparison of the scale with one containing visible numerical markings
      demonstrated that owners were heavily influenced by the presence of numbers,
      resulting in a loss of the scale's ability to generate continuous data. The
      presence of a traditional visual analogue scale was therefore essential. The
      scale was tested on 713 owners who presented their dogs for veterinary attention.
      Pruritus scores in 408 dogs with skin disease covered the full range of possible
      values (0 to 10). In 305 dogs with no skin disease, 90 owners gave a score
      greater than zero. Comparison of the scores seen in pruritic dogs, and dogs with
      no evidence of skin disease, allowed a 'normal range' of 0-1.9 to be established.
      The scale was able to discriminate between conditions typically regarded as
      pruritic or non-pruritic. When the scale was assessed for its ability to detect
      changes in pruritus score following treatment, a median reduction of 4.4 points
      was observed. The scale was also used to determine what magnitude of response
      owners would expect following treatment of their pruritic dogs. Only 12% would
      have been satisfied with a 50% reduction, a figure that is typically quoted as a
      satisfactory response in clinical trials of anti-pruritic drugs. As a result,
      alternative methods of assessing clinical trials are proposed. This study has
      shown the scale to be a valuable tool for clinical assessment of patients, and
      for monitoring treatment responses in clinical trials.

PMID- 19171022
TI  - ABCB1-1 Delta (MDR1-1 Delta) genotype is associated with adverse reactions in
      dogs treated with milbemycin oxime for generalized demodicosis.
AB  - Twenty-two dogs diagnosed with generalized demodicosis were treated with
      milbemycin oxime (MO) because of poor response to previous therapies or because
      the dog was a breed known to be susceptible to ivermectin toxicosis. Fifteen of
      the 22 dogs were herding breeds. Doses of MO ranged from 1.0 to 2.2 mg kg(-1)
      day(-1) per os. Cheek swab samples were obtained in order to determine each dog's
      ABCB1 genotype. Adverse drug reactions were recorded for each dog by the owners
      and/or veterinarians. The ABCB1-1 Delta genotype was significantly associated
      with the development of an adverse reaction (neurological toxicity) after
      treatment with MO. None of the 19 dogs with the wild-type ABCB1 allele
      experienced adverse reactions, whereas two dogs homozygous for the ABCB1-1 Delta
      mutation developed ataxia. Assessing the ABCB1-1 Delta genotype prior to MO
      administration may prevent neurological toxicity in these patients.

PMID- 19171023
TI  - Removal of cell surface heparan sulfate increases TACE activity and cleavage of
      ErbB4 receptor.
AB  - BACKGROUND: Nuclear localization of proteolytically formed intracellular fragment
      of ErbB4 receptor tyrosine kinase has been shown to promote cell survival, and
      nuclear localization of ErbB4 receptor has been described in human breast cancer.
      Tumor necrosis factor alpha converting enzyme (TACE) initiates the proteolytic
      cascade leading to ErbB4 intracellular domain formation. Interactions between
      matrix metalloproteases and heparan sulfate have been described, but the effect
      of cell surface heparan sulfate on TACE activity has not been previously
      described. RESULTS: As indicated by immunodetection of increased ErbB4
      intracellular domain formation and direct enzyme activity analysis, TACE activity
      was substantially amplified by enzymatic removal of cell surface heparan sulfate
      but not chondroitin sulfate. CONCLUSION: In this communication, we suggest a
      novel role for cell surface heparan sulfate. Removal of cell surface heparan
      sulfate led to increased formation of ErbB4 intracellular domain. As ErbB4
      intracellular domain has previously been shown to promote cell survival this
      finding may indicate a novel mechanism how HS degradation active in tumor tissue
      may favor cell survival.

PMID- 19171024
TI  - Effect of supplement with lactic-acid producing bacteria on fatigue and physical
      activity in patients with chronic fatigue syndrome.
AB  - Disturbances in intestinal microbial ecology and in the immune system of the host
      have been implicated as a part of the pathogenesis in chronic fatigue syndrome.
      Probiotic lactic acid producing bacteria have been shown to prevent and alleviate
      gastrointestinal disturbances and to normalize the cytokine profile which might
      be of an advantage for patients suffering from chronic fatigue syndrome. The aim
      of the study was to evaluate the effect of Lactobacillus paracasei ssp. paracasei
      F19, Lactobacillus acidophilus NCFB 1748 and Bifidobacterium lactis Bb12 on
      fatigue and physical activity in CFS patients. Fifteen patients fulfilling the
      criteria set by international researchers in the field at the US Centre for
      Disease Control and Prevention in 1994 for chronic fatigue syndrome, were
      included in the study. The patients had high fatigue severity scores and high
      disability scores. During the first two weeks baseline observations without
      treatment were assessed, succeeded by four weeks of intake of a probiotic product
      and a four-week follow-up period. The fatigue, health and physical activity was
      assessed by the use of the Visual Analogue Scales and the SF-12 Health Survey.
      Faecal samples were collected and the normal microflora was analysed.
      Neurocognitive functions improved during the study period while there were no
      significant changes in fatigue and physical activity scores. No major changes
      occurred in the gastrointestinal microflora. At the end of the study 6 of 15
      patients reported that they had improved according to the assessment described.
      The findings in this study that improvement of health is possible to achieve
      should encourage further studies with interventions with probiotics in patients
      with CFS.

PMID- 19171025
TI  - Improper excess light energy dissipation in Arabidopsis results in a metabolic
      reprogramming.
AB  - BACKGROUND: Plant performance is affected by the level of expression of PsbS, a
      key photoprotective protein involved in the process of feedback de-excitation
      (FDE), or the qE component of non-photochemical quenching, NPQ. RESULTS: In
      studies presented here, under constant laboratory conditions the metabolite
      profiles of leaves of wild-type Arabidopsis thaliana and plants lacking or
      overexpressing PsbS were very similar, but under natural conditions their
      differences in levels of PsbS expression were associated with major changes in
      metabolite profiles. Some carbohydrates and amino acids differed ten-fold in
      abundance between PsbS-lacking mutants and over-expressers, with wild-type plants
      having intermediate amounts, showing that a metabolic shift had occurred. The
      transcriptomes of the genotypes also varied under field conditions, and the genes
      induced in plants lacking PsbS were similar to those reportedly induced in plants
      exposed to ozone stress or treated with methyl jasmonate (MeJA). Genes involved
      in the biosynthesis of JA were up-regulated, and enzymes involved in this pathway
      accumulated. JA levels in the undamaged leaves of field-grown plants did not
      differ between wild-type and PsbS-lacking mutants, but they were higher in the
      mutants when they were exposed to herbivory. CONCLUSION: These findings suggest
      that lack of FDE results in increased photooxidative stress in the chloroplasts
      of Arabidopsis plants grown in the field, which elicits a response at the
      transcriptome level, causing a redirection of metabolism from growth towards
      defence that resembles a MeJA/JA response.

PMID- 19171026
TI  - Mercury from chlor-alkali plants: measured concentrations in food product sugar.
AB  - Mercury cell chlor-alkali products are used to produce thousands of other
      products including food ingredients such as citric acid, sodium benzoate, and
      high fructose corn syrup. High fructose corn syrup is used in food products to
      enhance shelf life. A pilot study was conducted to determine if high fructose
      corn syrup contains mercury, a toxic metal historically used as an anti
      microbial. High fructose corn syrup samples were collected from three different
      manufacturers and analyzed for total mercury. The samples were found to contain
      levels of mercury ranging from below a detection limit of 0.005 to 0.570
      micrograms mercury per gram of high fructose corn syrup. Average daily
      consumption of high fructose corn syrup is about 50 grams per person in the
      United States. With respect to total mercury exposure, it may be necessary to
      account for this source of mercury in the diet of children and sensitive
      populations.

PMID- 19171027
TI  - Tetraploid and hexaploid wheat varieties reveal large differences in expression
      of alpha-gliadins from homoeologous Gli-2 loci.
AB  - BACKGROUND: Alpha-gliadins form a multigene protein family encoded by multiple
      alpha-gliadin (Gli-2) genes at three genomic loci, Gli-A2, Gli-B2 and Gli-D2,
      respectively located on the homoeologous wheat chromosomes 6AS, 6BS, and 6DS.
      These proteins contain a number of important celiac disease (CD)-immunogenic
      domains. The alpha-gliadins expressed from the Gli-B2 locus harbour fewer
      conserved CD-epitopes than those from Gli-A2, whereas the Gli-D2 gliadins have
      the highest CD-immunogenic potential. In order to detect differences in the
      highly CD-immunogenic alpha-gliadin fraction we determined the relative
      expression level from the homoeologous Gli-2 loci in various tetraploid and
      hexaploid wheat genotypes by using a quantitative pyrosequencing method and by
      analyzing expressed sequence tag (EST) sequences. RESULTS: We detected large
      differences in relative expression levels of alpha-gliadin genes from the three
      homoeologous loci among wheat genotypes, both as relative numbers of expressed
      sequence tag (EST) sequences from specific varieties and when using a
      quantitative pyrosequencing assay specific for Gli-A2 genes. The relative Gli-A2
      expression level in a tetraploid durum wheat cultivar ('Probstdorfer Pandur') was
      41%. In genotypes derived from landraces, the Gli-A2 frequency varied between 12%
      and 58%. In some advanced hexaploid bread wheat cultivars the genes from locus
      Gli-B2 were hardly expressed (e.g., less than 5% in 'Lavett') but in others they
      made up more than 40% (e.g., in 'Baldus'). CONCLUSION: Here, we have shown that
      large differences exist in relative expression levels of alpha-gliadins from the
      homoeologous Gli-2 loci among wheat genotypes. Since the homoelogous genes differ
      in the amount of conserved CD-epitopes, screening for differential expression
      from the homoeologous Gli-2 loci can be employed for the pre-selection of wheat
      varieties in the search for varieties with very low CD-immunogenic potential.
      Pyrosequencing is a method that can be employed for such a 'gene family-specific
      quantitative transcriptome profiling'.

PMID- 19171028
TI  - Trait-specific tracking and determinants of body composition: a 7-year follow-up
      study of pubertal growth in girls.
AB  - BACKGROUND: Understanding how bone (BM), lean (LM) and fat mass (FM) develop
      through childhood, puberty and adolescence is vital since it holds key
      information regarding current and future health. Our study aimed to determine how
      BM, LM and FM track from prepuberty to early adulthood in girls and what factors
      are associated with intra- and inter-individual variation in these three tissues.
      METHODS: The study was a 7-year longitudinal cohort study. BM, LM and FM measured
      using dual-energy X-ray absorptiometry, self-reported dietary information,
      leisure time physical activity (LTPA) and other factors were assessed one to
      eight times in 396 girls aged 10 to 13 years (baseline), and in 255 mothers once.
      RESULTS: The location of a girl's BM, LM and FM in the lower, middle or upper
      part of the sample distribution was established before puberty and tracked in its
      percentile of origin over 7 years (r = 0.72 for BM, r = 0.61 for LM, and r = 0.65
      for FM all p < 0.001 first vs. last measurements' ranking). Seventy-three percent
      of those in the lowest quartile for BM and 69% for LM, and 79% of those in the
      highest quartile for FM at baseline remained in their quartile at 7-year follow
      up. Heritability was estimated to contribute 69% of the total variance of the BM,
      50% of the LM, and 57% of the FM. Besides body size, diet index (explaining 9% of
      variance), breast feeding duration (6%) and mother's BM (9%) predicted high BM.
      Diet index and high LTPA predicted high LM (24% and 14%, respectively), and low
      FM (25% and 12%, respectively), and low level of parental education predicted
      high FM (4%). CONCLUSION: Individual levels of BM, LM and FM are established
      before puberty and track in a trait-specific manner until early adulthood. Girls
      who are prone to develop low BM and LM and high FM in adulthood can be identified
      in prepuberty. The developments of three components of body composition are inter
      related during growth. BM was the most heritable trait while LM the most
      environmentally modifiable. Diet and physical activity played an important role
      in increasing LM and preventing the accumulation of excessive FM.

PMID- 19171029
TI  - Evaluating the impact of scoring parameters on the structure of intra-specific
      genetic variation using RawGeno, an R package for automating AFLP scoring.
AB  - BACKGROUND: Since the transfer and application of modern sequencing technologies
      to the analysis of amplified fragment-length polymorphisms (AFLP), evolutionary
      biologists have included an increasing number of samples and markers in their
      studies. Although justified in this context, the use of automated scoring
      procedures may result in technical biases that weaken the power and reliability
      of further analyses. RESULTS: Using a new scoring algorithm, RawGeno, we show
      that scoring errors--in particular "bin oversplitting" (i.e. when variant sizes
      of the same AFLP marker are not considered as homologous) and "technical
      homoplasy" (i.e. when two AFLP markers that differ slightly in size are
      mistakenly considered as being homologous)--induce a loss of discriminatory
      power, decrease the robustness of results and, in extreme cases, introduce
      erroneous information in genetic structure analyses. In the present study, we
      evaluate several descriptive statistics that can be used to optimize the scoring
      of the AFLP analysis, and we describe a new statistic, the information content
      per bin (Ibin) that represents a valuable estimator during the optimization
      process. This statistic can be computed at any stage of the AFLP analysis without
      requiring the inclusion of replicated samples. Finally, we show that downstream
      analyses are not equally sensitive to scoring errors. Indeed, although a
      reasonable amount of flexibility is allowed during the optimization of the
      scoring procedure without causing considerable changes in the detection of
      genetic structure patterns, notable discrepancies are observed when estimating
      genetic diversities from differently scored datasets. CONCLUSION: Our algorithm
      appears to perform as well as a commercial program in automating AFLP scoring, at
      least in the context of population genetics or phylogeographic studies. To our
      knowledge, RawGeno is the only freely available public-domain software for fully
      automated AFLP scoring, from electropherogram files to user-defined working
      binary matrices. RawGeno was implemented in an R CRAN package (with an user
      friendly GUI) and can be found at http://sourceforge.net/projects/rawgeno.

PMID- 19171030
TI  - Characterization of culture-positive adenovirus serotypes from respiratory
      specimens in Toronto, Ontario, Canada: September 2007-June 2008.
AB  - This study describes the prevalence of culture-positive adenovirus serotypes in
      culture-positive respiratory specimens sent to the Central Public Health
      Laboratory, Toronto, Ontario, Canada for the period September 2007-June 2008.
      Total nucleic acid was extracted from virus cultures using an automated
      extraction method followed by polymerase chain reaction and Sanger sequencing of
      the adenovirus hexon gene hypervariable region 7. 73% of specimens (n = 70) were
      from patients < or = 4 years of age. Of the 96 adenovirus isolates, the most
      common identified serotypes were serotype 3 (n = 44, 46%), serotype 2 (n = 25,
      26%), serotype 1 (n = 17, 18%), and serotype 21 (n = 5, 5%). Adenovirus serotype
      14 was not found in this study group. The leading serotype, Ad3, was identified
      throughout the duration of the study period. Molecular methods allow for the
      determination of circulating adenovirus serotypes and be used to document the
      spread of highly virulent adenoviral serotypes into a region.

PMID- 19171032
TI  - The hierarchically organized splitting of chromosomal bands for all human
      chromosomes.
AB  - BACKGROUND: Chromosome banding is widely used in cytogenetics. However, the
      biological nature of hierarchically organized splitting of chromosomal bands of
      human chromosomes is an enigma and has not been, as yet, studied. RESULTS: Here
      we present for the first time the hierarchically organized splitting of
      chromosomal bands in their sub-bands for all human chromosomes. To do this, array
      proved multicolor banding (aMCB) probe-sets for all human chromosomes were
      applied to normal metaphase spreads of three different G-band levels. We
      confirmed for all chromosomes to be a general principle that only Giemsa-dark
      bands split into dark and light sub-bands, as we demonstrated previously by
      chromosome stretching. Thus, the biological band splitting is in > 50% of the sub
      bands different than implemented by the ISCN nomenclature suggesting also a
      splitting of G-light bands. Locus-specific probes exemplary confirmed the results
      of MCB. CONCLUSION: Overall, the present study enables a better understanding of
      chromosome architecture. The observed difference of biological and ISCN band
      splitting may be an explanation why mapping data from human genome project do not
      always fit the cytogenetic mapping.

PMID- 19171031
TI  - Age-specific symptom prevalence in women 35-64 years old: a population-based
      study.
AB  - BACKGROUND: Symptom prevalence is generally believed to increase with age. The
      aim of this study was to evaluate the age specific prevalence of 30 general
      symptoms among Swedish middle-aged women. METHODS: A cross-sectional postal
      questionnaire study in seven Swedish counties in a random sample of 4,200 women
      35-64 years old, with 2,991 responders. Thirty general symptoms included in the
      Complaint Score subscale of the Gothenburg Quality of Life Instrument were used.
      RESULTS: Four groups of age specific prevalence patterns were identified after
      adjustment for the influence of educational level, perceived health and mood,
      body mass index, smoking habits, use of hormone replacement therapy, and use of
      other symptom relieving therapy. Only five symptoms (insomnia, leg pain, joint
      pain, eye problems and impaired hearing) increased significantly with age. Eleven
      symptoms (general fatigue, headache, irritability, melancholy, backache,
      exhaustion, feels cold, cries easily, abdominal pain, dizziness, and nausea)
      decreased significantly with age. Two symptoms (sweating and impaired
      concentration) had a biphasic course with a significant increase followed by a
      significant decrease. The remaining twelve symptoms (difficulty in relaxing,
      restlessness, overweight, coughing, breathlessness, diarrhoea, chest pain,
      constipation, nervousness, poor appetite, weight loss, and difficulty in
      urinating) had stable prevalence with age. CONCLUSION: Symptoms did not
      necessarily increase with age instead symptoms related to stress-tension
      depression decreased.

PMID- 19171033
TI  - GRIP: A web-based system for constructing Gold Standard datasets for protein
      protein interaction prediction.
AB  - BACKGROUND: Information about protein interaction networks is fundamental to
      understanding protein function and cellular processes. Interaction patterns among
      proteins can suggest new drug targets and aid in the design of new therapeutic
      interventions. Efforts have been made to map interactions on a proteomic-wide
      scale using both experimental and computational techniques. Reference datasets
      that contain known interacting proteins (positive cases) and non-interacting
      proteins (negative cases) are essential to support computational prediction and
      validation of protein-protein interactions. Information on known interacting and
      non interacting proteins are usually stored within databases. Extraction of these
      data can be both complex and time consuming. Although, the automatic construction
      of reference datasets for classification is a useful resource for researchers no
      public resource currently exists to perform this task. RESULTS: GRIP (Gold
      Reference dataset constructor from Information on Protein complexes) is a web
      based system that provides researchers with the functionality to create reference
      datasets for protein-protein interaction prediction in Saccharomyces cerevisiae.
      Both positive and negative cases for a reference dataset can be extracted,
      organised and downloaded by the user. GRIP also provides an upload facility
      whereby users can submit proteins to determine protein complex membership. A
      search facility is provided where a user can search for protein complex
      information in Saccharomyces cerevisiae. CONCLUSION: GRIP is developed to
      retrieve information on protein complex, cellular localisation, and physical and
      genetic interactions in Saccharomyces cerevisiae. Manual construction of
      reference datasets can be a time consuming process requiring programming
      knowledge. GRIP simplifies and speeds up this process by allowing users to
      automatically construct reference datasets. GRIP is free to access at
      http://rosalind.infj.ulst.ac.uk/GRIP/.

PMID- 19171034
TI  - Depression and anxiety as major determinants of neck pain: a cross-sectional
      study in general practice.
AB  - BACKGROUND: Although psychosocial factors are known to be highly linked with neck
      pain, current therapies focus on somatically based interventions such as
      medicinal or manipulatory therapies. This study examines how socio-demographic,
      psychosocial and medical history and health-promoting lifestyle factors interact
      with neck pain in general practice patients. METHODS: This is a cross-sectional
      survey including 448 patients from a general practice setting in Germany.
      Participants completed a comprehensive questionnaire including the Neck Pain and
      Disability Scale German version (NPAD-d) and the Hospital Anxiety and Depression
      Scale. Crude and adjusted regression analyses were done to assess the
      relationship between neck pain and socio-demographic, psychosocial and medical
      history and health-promoting lifestyle factors. RESULTS: Both in crude and
      adjusted regression analyses, depression and anxiety were highly significantly
      linked with increasing levels of neck pain. Educational level, deficits in social
      support and physical exercise were associated with neck pain in bivariate
      analyses, but these associations did not persist with adjustment for depression
      and anxiety. When investigating levels of depression and anxiety by NPAD-d
      quartile subgroups, those who were identified to have depressive mood or to be
      anxious were very likely to be in the group with the highest levels of neck pain.
      CONCLUSION: The higher the neck pain level, the more attention should be paid to
      psychosocial distress as a related burden. Further research is needed to
      elucidate the causality and the direction of the association between psychosocial
      distress and neck pain and to determine the benefit of psychosocial
      interventions.

PMID- 19171035
TI  - Allergies and major depression: a longitudinal community study.
AB  - BACKGROUND: Cross-sectional studies have reported associations between allergies
      and major depression but in the absence of longitudinal data, the implications of
      this association remain unclear. Our goal was to examine this association from a
      longitudinal perspective. METHODS: The data source was the Canadian National
      Population Health Survey (NPHS). This study included a short form version of the
      Composite International Diagnostic Interview (CIDI-SF) to assess major depression
      and also included self report items for professionally diagnosed allergies of two
      types: non-food allergies and food allergies. A longitudinal cohort was followed
      between 1994 and 2002. Proportional hazards models for grouped time data were
      used to estimate unadjusted and adjusted hazard ratios. RESULTS: A slightly
      increased incidence of non-food allergies in respondents with major depression
      was observed: adjusted hazard ratio 1.2 (95% 1.0 - 1.5, p = 0.046). Some evidence
      for an increased incidence of major depression in association with non-food
      allergies was found in unadjusted analyses, but the association did not persist
      after multivariate adjustment. Food allergies were not associated with major
      depression incidence, nor was major depression associated with an increased
      incidence of food allergies. CONCLUSION: Findings from the present study support
      the idea that major depression is associated with an increased risk of developing
      non-food allergies. An effect in the opposite direction could not be confirmed.
      The observed effect may be due to shared genetic factors, epigenetic factors, or
      immunological changes that occur during depression.

PMID- 19171036
TI  - Characterization of SV-40 Tag rats as a model to study prostate cancer.
AB  - BACKGROUND: Prostate cancer is the second most frequently diagnosed cancer in
      men. Animal models that closely mimic clinical disease in humans are invaluable
      tools in the fight against prostate cancer. Recently, a Simian Virus-40 T-antigen
      (SV-40 Tag) targeted probasin promoter rat model was developed. This model,
      however, has not been extensively characterized; hence we have investigated the
      ontogeny of prostate cancer and determined the role of sex steroid receptor and
      insulin-like growth factor-1 (IGF-1) signaling proteins in the novel SV-40 Tag
      rat. METHODS: The SV-40 Tag rat was histopathologically characterized for time to
      tumor development, incidence and multiplicity and in the ventral, dorsal, lateral
      and anterior lobes of the prostate. Immunoassay techniques were employed to
      measure cell proliferation, apoptosis, and sex steroid receptor and growth factor
      signaling-related proteins. Steroid hormone concentrations were measured via
      coated well enzyme linked immunosorbent assay (ELISA) kits. RESULTS: Prostatic
      intraepithelial neoplasia (PIN) and well-differentiated prostate cancer developed
      as early as 2 and 10 weeks of age, respectively in the ventral prostate (VP)
      followed by in the dorsolateral (DLP). At 8 weeks of age, testosterone and
      dihydrotestosterone (DHT) concentrations in SV-40 Tag rats were increased when
      compared to non-transgenic rats. High cell proliferation and apoptotic indices
      were found in VP and DLP of transgenic rats. Furthermore, we observed increased
      protein expression of androgen receptor, IGF-1, IGF-1 receptor, and extracellular
      signal-regulated kinases in the prostates of SV-40 Tag rats. CONCLUSION: The
      rapid development of PIN and prostate cancer in conjunction with the large
      prostate size makes the SV-40 Tag rat a useful model for studying prostate
      cancer. This study provides evidence of the role of sex steroid and growth factor
      proteins in prostate cancer development and defines appropriate windows of
      opportunity for preclinical trials and aids in the rational design of
      chemoprevention, intervention, regression, and therapeutic studies using prostate
      cancer rodent models.

PMID- 19171037
TI  - Bifurcation analysis informs Bayesian inference in the Hes1 feedback loop.
AB  - BACKGROUND: Ordinary differential equations (ODEs) are an important tool for
      describing the dynamics of biological systems. However, for ODE models to be
      useful, their parameters must first be calibrated. Parameter estimation, that is,
      finding parameter values given experimental data, is an inference problem that
      can be treated systematically through a Bayesian framework.A Markov chain Monte
      Carlo approach can then be used to sample from the appropriate posterior
      probability distributions, provided that suitable prior distributions can be
      found for the unknown parameter values. Choosing these priors is therefore a
      vital first step in the inference process. We study here a negative feedback loop
      in gene regulation where an ODE incorporating a time delay has been proposed as a
      realistic model and where experimental data is available. Our aim is to show that
      a priori mathematical analysis can be exploited in the choice of priors. RESULTS:
      By focussing on the onset of oscillatory behaviour through a Hopf Bifurcation, we
      derive a range of analytical expressions and constraints that link the model
      parameters to the observed dynamics of the system. Computational tests on both
      simulated and experimental data emphasise the usefulness of this analysis.
      CONCLUSION: Mathematical analysis not only gives insights into the possible
      dynamical behaviour of gene expression models, but can also be used to inform the
      choice of priors when parameters are inferred from experimental data in a
      Bayesian setting.

PMID- 19171038
TI  - Assessment of ePrescription quality: an observational study at three mail-order
      pharmacies.
AB  - BACKGROUND: The introduction of electronic transfer of prescriptions (ETP) or
      ePrescriptions in ambulatory health care has been suggested to have a positive
      impact on the prescribing and dispensing processes. Thereby, implying that
      ePrescribing can improve safety, quality, efficiency, and cost-effectiveness. In
      December 2007, 68% of all new prescriptions were transferred electronically in
      Sweden. The aim of the present study was to assess the quality of ePrescriptions
      by comparing the proportions of ePrescriptions and non-electronic prescriptions
      necessitating a clarification contact (correction, completion or change) with the
      prescriber at the time of dispensing. METHODS: A direct observational study was
      performed at three Swedish mail-order pharmacies which were known to dispense a
      large proportion of ePrescriptions (38-75%). Data were gathered on all
      ePrescriptions dispensed at these pharmacies over a three week period in February
      2006. All clarification contacts with prescribers were included in the study and
      were classified and assessed in comparison with all drug prescriptions dispensed
      at the same pharmacies over the specified period. RESULTS: Of the 31225
      prescriptions dispensed during the study period, clarification contacts were made
      for 2.0% (147/7532) of new ePrescriptions and 1.2% (79/6833) of new non
      electronic prescriptions. This represented a relative risk (RR) of 1.7 (95% CI
      1.3-2.2) for new ePrescriptions compared to new non-electronic prescriptions. The
      increased RR was mainly due to 'Dosage and directions for use', which had an RR
      of 7.6 (95% CI 2.8-20.4) when compared to other clarification contacts. In all,
      89.5% of the suggested pharmacist interventions were accepted by the prescriber,
      77.7% (192/247) as suggested and an additional 11.7% (29/247) after a
      modification during contact with the prescriber. CONCLUSION: The increased
      proportion of prescriptions necessitating a clarification contact for new
      ePrescriptions compared to new non-electronic prescriptions indicates the need
      for an increased focus on quality aspects in ePrescribing deployment. ETP
      technology should be developed towards a two-way communication between the
      prescriber and the pharmacist with automated checks of missing, inaccurate, or
      ambiguous information. This would enhance safety and quality for the patient and
      also improve efficiency and cost-effectiveness within the health care system.

PMID- 19171039
TI  - Invasive pulmonary aspergillosis 10 years post bone marrow transplantation: a
      case report.
AB  - INTRODUCTION: Invasive pulmonary aspergillosis is a leading cause of mortality
      and morbidity in bone marrow transplant recipients. Establishing the diagnosis
      remains a challenge for clinicians working in acute care setting. However, prompt
      diagnosis and treatment can lead to favourable outcomes CASE PRESENTATION: We
      report a case of invasive aspergillosis occurring in a 39-year-old Caucasian
      female 10 years after an allogeneic haematopoietic bone marrow transplant, and 5
      years after stopping all immunosuppression. Possible risk factors include
      bronchiolitis obliterans and exposure to building dust (for example, handling her
      husband's dusty overalls). There are no similar case reports in the literature at
      this time. CONCLUSION: High clinical suspicion, especially in the setting of
      failure to respond to broad-spectrum antibiotics, should alert clinicians to the
      possibility of invasive pulmonary aspergillosis, which, in this case, responded
      to antifungal therapy.

PMID- 19171040
TI  - Red blood cell glutathione peroxidase activity in female nulligravid and pregnant
      rats.
AB  - BACKGROUND: The alterations of the glutathione peroxidase enzyme complex system
      occur in physiological conditions such as aging and oxidative stress consequent
      to strenuous exercise. METHODS: Authors optimize the spectrophotometric method to
      measure glutathione peroxidase activity in rat red blood cell membranes. RESULTS:
      The optimization, when applied to age paired rats, both nulligravid and pregnant,
      shows that pregnancy induces, at seventeen d of pregnancy, an increase of both
      reactive oxygen substance concentration in red blood cells and membrane
      glutathione peroxidase activity. CONCLUSION: The glutathione peroxidase increase
      in erythrocyte membranes is induced by systemic oxidative stress long lasting rat
      pregnancy.

PMID- 19171041
TI  - Hypocellular acute myeloid leukemia with bone marrow necrosis in young patients:
      two case reports.
AB  - INTRODUCTION: Hypocellular variants of acute myeloid leukemia are very rare and
      almost always occur in old aged patients. In contrast, hypocellular acute
      lymphoblastic leukemia usually occurs in children. CASE PRESENTATION: We report
      two Indian patients with hypocellular acute myeloid leukemia, a 32-year-old woman
      and a 13-year-old boy. Interestingly, one of the patients also showed bone marrow
      necrosis. CONCLUSION: Hypocellular acute myeloid leukemia is a rare entity and
      can affect young individuals. It can be considered as a rare cause of bone marrow
      necrosis.

PMID- 19171042
TI  - Autocrine regulation of cell proliferation by estrogen receptor-alpha in estrogen
      receptor-alpha-positive breast cancer cell lines.
AB  - BACKGROUND: Estrogen receptor-alpha (ERalpha) is essential for mammary gland
      development and is a major oncogene in breast cancer. Since ERalpha is not
      colocalized with the cell proliferation marker Ki-67 in the normal mammary glands
      and the majority of primary breast tumors, it is generally believed that
      paracrine regulation is involved in ERalpha mediated cell proliferation. In the
      paracrine model, ERalpha-positive cells don't proliferate but will release some
      paracrine growth factors to stimulate the neighboring cells to proliferate. In a
      subpopulation of cancer cells in some primary breast tumors, however, ERalpha
      does colocalize with the cell proliferation marker Ki-67, suggesting an autocrine
      regulation by ERalpha in some primary breast tumors. METHODS: Colocalization of
      ERalpha with Ki-67 in ERalpha-positive breast cancer cell lines (MCF-7, T47D, and
      ZR75-1) was evaluated by immunofluorescent staining. Cell cycle phase dependent
      expression of ERalpha was determined by co-immunofluorescent staining of ERalpha
      and the major cyclins (D, E, A, B), and by flow cytometry analysis of ERalphahigh
      cells. To further confirm the autocrine action of ERalpha, MCF-7 cells were
      growth arrested by ICI182780 treatment, followed by treatment with EGFR
      inhibitor, before estrogen stimulation and analyses for colocalization of Ki-67
      and ERalpha and cell cycle progression. RESULTS: Colocalization of ERalpha with
      Ki-67 was present in all three ERalpha-positive breast cancer cell lines. Unlike
      that in the normal mammary glands and the majority of primary breast tumors,
      ERalpha is highly expressed throughout the cell cycle in MCF-7 cells. Without E2
      stimulation, MCF-7 cells released from ICI182780 treatment remain at G1 phase. E2
      stimulation of ICI182780 treated cells, however, promotes the expression and
      colocalization of ERalpha and Ki-67 as well as the cell cycle progressing through
      the S and G2/M phases. Inhibition of EGFR signaling does not inhibit the
      autocrine action of ERalpha. CONCLUSION: Our data indicate that ERalpha can
      mediate estrogen-induced cell proliferation in an autocrine mode in ERalpha
      positive breast cancer cell lines. All of the three ERalpha-positive cell lines
      used in our study showed colocalization of ERalpha and Ki-67, indicating that
      these cell lines might be originated from primary tumor cells with autocrine
      regulation.

PMID- 19171043
TI  - Different inflammatory responses are associated with Ureaplasma parvum-induced
      UTI and urolith formation.
AB  - BACKGROUND: Epidemiologic studies show a strong association between Ureaplasmas
      and urogenital tract disease in humans. Since healthy humans can be colonized
      with Ureaplasmas, its role as a pathogen remains controversial. In order to begin
      to define the role of the host in disease, we developed a rodent model of urinary
      tract infection (UTI) using Fischer 344 (F344) rats. Animals were inoculated with
      sterile broth, 10(1), 10(3), 10(5), 10(7), or 10(9) log CFU of a rat-adapted
      strain of Ureaplasma parvum. RESULTS: Infected animals exhibited two distinct
      profiles, asymptomatic UTI and UTI complicated with struvite urolithiasis.
      Inoculum dose of U. parvum affected the incidence of UTI, and 50% to 57% of
      animals inoculated with >or= 10(7) CFU of U. parvum remained infected (p < 0.04).
      However, inoculum dose did not influence immune response to U. parvum.
      Asymptomatic UTI was characterized by a minimal immune response that was
      predominantly monocytic and lymphocytic, with limited lesions, and elevated
      urinary levels of IFN-gamma, IL-18 and MCP-1 (P <or= 0.02). UTI complicated with
      struvite formation was characterized by an exaggerated immune response that was
      mostly neutrophilic (P <or= 0.0001), with lesions that showed extensive
      uroepithelial hyperplasia (P <or= 0.0001), and a predominance of IL-1 alpha, IL-1
      beta, and GRO/KC in the urine (P <or= 0.02). Animals with asymptomatic UTI also
      had a significantly high rate of kidney infection (P <or= 0.0005). CONCLUSION:
      Complications associated with U. parvum infection are primarily dependent upon
      host-specific factors rather than Ureaplasma microbial load. The immune response
      in F344 rats is similar to that which occurs in humans with ureaplasmal
      associated disease. Therefore, this model of infection is a useful tool for
      elucidating U. parvum-host interactions that confer UTI and disease.

PMID- 19171044
TI  - Fingerprinting antioxidative activities in plants.
AB  - BACKGROUND: A plethora of concurrent cellular activities is mobilised in the
      adaptation of plants to adverse environmental conditions. This response can be
      quantified by physiological experiments or metabolic profiling. The intention of
      this work is to reduce the number of metabolic processes studied to a minimum of
      relevant parameters with a maximum yield of information. Therefore, we inspected
      'summary parameters' characteristic for whole classes of antioxidative
      metabolites and key enzymes. RESULTS: Three bioluminescence assays are presented.
      A horseradish peroxidase-based total antioxidative capacity (TAC) assay is used
      to probe low molecular weight antioxidants. Peroxidases are quantified by their
      luminol converting activity (LUPO). Finally, we quantify high molecular weight
      superoxide anion scavenging activity (SOSA) using coelenterazine.Experiments with
      Lepidium sativum L. show how salt, drought, cold, and heat influence the
      antioxidative system represented here by TAC, LUPO, SOSA, catalase, and
      glutathione reductase (GR). LUPO and SOSA run anti-parallel under all
      investigated stress conditions suggesting shifts in antioxidative functions
      rather than formation of antioxidative power. TAC runs in parallel with GR. This
      indicates that a majority of low molecular weight antioxidants in plants is
      represented by glutathione. CONCLUSION: The set of assays presented here is
      capable of characterising antioxidative activities in plants. It is inexpensive,
      quick and reproducible and delivers quantitative data. 'Summary parameters' like
      TAC, LUPO, and SOSA are quantitative traits which may be promising for
      implementation in high-throughput screening for robustness of novel mutants,
      transgenics, or breeds.

PMID- 19171045
TI  - Posterior lung herniation after a coughing spell: a case report.
AB  - Lung hernias are rare, occurring most commonly after trauma or surgery.
      Spontaneous lung hernias are even rarer and have only been reported as occurring
      anteriorly. We present a 72-year-old male who developed a spontaneous posterior
      lung hernia after a severe coughing episode. We describe the evaluation and
      surgical management of this unusual condition and provide a brief review of the
      literature.

PMID- 19171046
TI  - Gene expression profile analysis of human hepatocellular carcinoma using SAGE and
      LongSAGE.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers
      worldwide and the second cancer killer in China. The initiation and malignant
      transformation of cancer result from accumulation of genetic changes in the
      sequences or expression level of cancer-related genes. It is of particular
      importance to determine gene expression profiles of cancers on a global scale.
      SAGE and LongSAGE have been developed for this purpose. METHODS: We performed
      SAGE in normal liver and HCC samples as well as the liver cancer cell line HepG2.
      Meanwhile, the same HCC sample was simultaneously analyzed using LongSAGE.
      Computational analysis was carried out to identify differentially expressed genes
      between normal liver and HCC which were further validated by real-time
      quantitative RT-PCR. RESULTS: Approximately 50,000 tags were sequenced for each
      of the four libraries. Analysis of the technical replicates of HCC indicated that
      excluding the low abundance tags, the reproducibility of SAGE data is high (R =
      0.97). Compared with the gene expression profile of normal liver, 224 genes
      related to biosynthesis, cell proliferation, signal transduction, cellular
      metabolism and transport were identified to be differentially expressed in HCC.
      Overexpression of some transcripts selected from SAGE data was validated by real
      time quantitative RT-PCR. Interestingly, sarcoglycan-epsilon (SGCE) and
      paternally expressed gene (PEG10) which is a pair of close neighboring genes on
      chromosome 7q21, showed similar enhanced expression patterns in HCC, implicating
      that a common mechanism of deregulation may be shared by these two genes.
      CONCLUSION: Our study depicted the expression profile of HCC on a genome-wide
      scale without the restriction of annotation databases, and provided novel
      candidate genes that might be related to HCC.

PMID- 19171047
TI  - Bone marrow lesions from osteoarthritis knees are characterized by sclerotic bone
      that is less well mineralized.
AB  - INTRODUCTION: Although the presence of bone marrow lesions (BMLs) on magnetic
      resonance images is strongly associated with osteoarthritis progression and pain,
      the underlying pathology is not well established. The aim of the present study
      was to evaluate the architecture of subchondral bone in regions with and without
      BMLs from the same individual using bone histomorphometry. METHODS:
      Postmenopausal female subjects (n = 6, age 48 to 90 years) with predominantly
      medial compartment osteoarthritis and on a waiting list for total knee
      replacement were recruited. To identify the location of the BMLs, subjects had a
      magnetic resonance imaging scan performed on their study knee prior to total knee
      replacement using a GE 1.5 T scanner with a dedicated extremity coil. An axial
      map of the tibial plateau was made, delineating the precise location of the BML.
      After surgical removal of the tibial plateau, the BML was localized using the
      axial map from the magnetic resonance image and the lesion excised along with a
      comparably sized bone specimen adjacent to the BML and from the contralateral
      compartment without a BML. Cores were imaged via microcomputed tomography, and
      the bone volume fraction and tissue mineral density were calculated for each
      core. In addition, the thickness of the subchondral plate was measured, and the
      following quantitative metrics of trabecular structure were calculated for the
      subchondral trabecular bone in each core: trabecular number, thickness, and
      spacing, structure model index, connectivity density, and degree of anisotropy.
      We computed the mean and standard deviation for each parameter, and the
      unaffected bone from the medial tibial plateau and the bone from the lateral
      tibial plateau were compared with the affected BML region in the medial tibial
      plateau. RESULTS: Cores from the lesion area displayed increased bone volume
      fraction but reduced tissue mineral density. The samples from the subchondral
      trabecular lesion area exhibited increased trabecular thickness and were also
      markedly more plate-like than the bone in the other three locations, as evidenced
      by the lower value of the structural model index. Other differences in structure
      that were noted were increased trabecular spacing and a trend towards decreased
      trabecular number in the cores from the medial location as compared with the
      contralateral location. CONCLUSIONS: Our preliminary data localize specific
      changes in bone mineralization, remodeling and defects within BMLs features that
      are adjacent to the subchondral plate. These BMLs appear to be sclerotic compared
      with unaffected regions from the same individual based on the increased bone
      volume fraction and increased trabecular thickness. The mineral density in these
      lesions, however, is reduced and may render this area to be mechanically
      compromised, and thus susceptible to attrition.

PMID- 19171048
TI  - Combined adenocarcinoid and mucinous cystadenoma of the appendix: a case report.
AB  - INTRODUCTION: Adenocarcinoid of the appendix is a rare malignant tumour with
      features of both adenocarcinoma and carcinoid, showing both epithelial and
      endocrine differentiation. Mucinous cystadenoma is the commonest of the benign
      neoplasms of the appendix, with an incidence of 0.6% in appendicectomy specimens.
      We report a rare combination of these tumours and discuss the latest treatment
      options. To the best of our knowledge, only six cases have been reported in the
      literature to date. CASE PRESENTATION: A 71-year-old Caucasian man presented to
      our department with a right iliac fossa mass associated with pain. Laparoscopy
      revealed an adenocarcinoid of the appendix in combination with mucinous
      cystadenoma. He underwent a radical right hemicolectomy with clear margins and
      lymph nodes. CONCLUSION: Adenocarcinoids account for 2% of primary appendiceal
      malignancies. Most tumours are less than 2 cm in diameter and 20% of them
      metastasize to the ovaries. The mean age for presentation is 59 years and the 5
      year survival rate ranges from 60% to 84%. Right hemicolectomy is generally
      advised if any of the following features are present: tumours greater than 2 cm,
      involvement of resection margins, greater than 2 mitoses/10 high-power fields on
      histology, extension of tumour beyond serosa. Chemotherapy mostly with 5
      Fluorouracil and Leucovorin is advised for remnant disease after surgery.
      Cytoreductive surgery with intraperitoneal chemotherapy can offer improved
      survival for advanced peritoneal dissemination.

PMID- 19171049
TI  - Analysis of a conserved RGE/RGD motif in HCV E2 in mediating entry.
AB  - BACKGROUND: Hepatitis C virus (HCV) encodes two transmembrane glycoproteins E1
      and E2 which form a heterodimer. E1 is believed to mediate fusion while E2 has
      been shown to bind cellular receptors. It is clear that HCV uses a multi-receptor
      complex to gain entry into susceptible cells, however key elements of this
      complex remain elusive. In this study, the role of a highly conserved RGE/RGD
      motif of HCV E2 glycoprotein in viral entry was examined. The effect of each
      substitution mutation in this motif was tested by challenging susceptible cell
      lines with mutant HCV E1E2 pseudotyped viruses generated using a lentiviral
      system (HCVpp). In addition to assaying infectivity, producer cell expression and
      HCVpp incorporation of HCV E2 proteins, CD81 binding profiles, and conformation
      of mutants were examined. RESULTS: Based on these characteristics, mutants either
      displayed wt characteristics (high infectivity [> or = 90% of wt HCVpp], CD81
      binding, E1E2 expression, and incorporation into viral particles and proper
      conformation) or very low infectivity (< or = 20% of wt HCVpp). Only amino acid
      substitutions of the 3rd position (D or E) resulted in wt characteristics as long
      as the negative charge was maintained or a neutral alanine was introduced. A
      change in charge to a positive lysine, disrupted HCVpp infectivity at this
      position. CONCLUSION: Although most amino acid substitutions within this
      conserved motif displayed greatly reduced HCVpp infectivity, they retained
      soluble CD81 binding, proper E2 conformation, and incorporation into HCVpp. Our
      results suggest that although RGE/D is a well-defined integrin binding motif, in
      this case the role of these three hyperconserved amino acids does not appear to
      be integrin binding. As the extent of conservation of this region extends well
      beyond these three amino acids, we speculate that this region may play an
      important role in the structure of HCV E2 or in mediating the interaction with
      other factor(s) during viral entry.

PMID- 19171050
TI  - Assigning strains to bacterial species via the internet.
AB  - BACKGROUND: Methods for assigning strains to bacterial species are cumbersome and
      no longer fit for purpose. The concatenated sequences of multiple house-keeping
      genes have been shown to be able to define and circumscribe bacterial species as
      sequence clusters. The advantage of this approach (multilocus sequence analysis;
      MLSA) is that, for any group of related species, a strain database can be
      produced and combined with software that allows query strains to be assigned to
      species via the internet. As an exemplar of this approach, we have studied a
      group of species, the viridans streptococci, which are very difficult to assign
      to species using standard taxonomic procedures, and have developed a website that
      allows species assignment via the internet. RESULTS: Seven house-keeping gene
      sequences were obtained from 420 streptococcal strains to produce a viridans
      group database. The reference tree produced using the concatenated sequences
      identified sequence clusters which, by examining the position on the tree of the
      type strain of each viridans group species, could be equated with species
      clusters. MLSA also identified clusters that may correspond to new species, and
      previously described species whose status needs to be re-examined. A generic
      website and software for electronic taxonomy was developed. This site
      http://www.eMLSA.net allows the sequences of the seven gene fragments of a query
      strain to be entered and for the species assignment to be returned, according to
      its position within an assigned species cluster on the reference tree.
      CONCLUSION: The MLSA approach resulted in the identification of well-resolved
      species clusters within this taxonomically challenging group and, using the
      software we have developed, allows unknown strains to be assigned to viridans
      species via the internet. Submission of new strains will provide a growing
      resource for the taxonomy of viridans group streptococci, allowing the
      recognition of potential new species and taxonomic anomalies. More generally, as
      the software at the MLSA website is generic, MLSA schemes and strain databases
      for other groups of related species can be hosted at this website, providing a
      portal for microbial electronic taxonomy.

PMID- 19171051
TI  - Spatial analysis of malaria incidence at the village level in areas with unstable
      transmission in Ethiopia.
AB  - BACKGROUND: Malaria is the leading cause of morbidity and mortality in Ethiopia,
      accounting for over five million cases and thousands of deaths annually. The
      risks of morbidity and mortality associated with malaria are characterized by
      spatial and temporal variation across the country. This study examines the
      spatial and temporal patterns of malaria transmission at the local level and
      implements a risk mapping tool to aid in monitoring and disease control
      activities. METHODS: In this study, we examine the global and local patterns of
      malaria distribution in 543 villages in East Shoa, central Ethiopia using
      individual-level morbidity data collected from six laboratory and treatment
      centers between September 2002 and August 2006. RESULTS: Statistical analysis of
      malaria incidence by sex, age, and village through time reveal the presence of
      significant spatio-temporal variations. Poisson regression analysis shows a
      decrease in malaria incidence with increasing age. A significant difference in
      the malaria incidence density ratio (IDRs) is detected in males but not in
      females. A significant decrease in the malaria IDRs with increasing age is
      captured by a quadratic model. Local spatial statistics reveals clustering or hot
      spots within a 5 and 10 km distance of most villages in the study area. In
      addition, there are temporal variations in malaria incidence. CONCLUSION: Malaria
      incidence varies according to gender and age, with males age 5 and above showing
      a statistically higher incidence. Significant local clustering of malaria
      incidence occurs between pairs of villages within 1-10 km distance lags. Malaria
      incidence was higher in 2002-2003 than in other periods of observation. Malaria
      hot spots are displayed as risk maps that are useful for monitoring and spatial
      targeting of prevention and control measures against the disease.

PMID- 19171052
TI  - Selective amplification of glucocorticoid anti-inflammatory activity through
      synergistic multi-target action of a combination drug.
AB  - INTRODUCTION: Glucocorticoids are a mainstay of anti-inflammatory therapy, but
      significant adverse effects ultimately limit their utility. Previous efforts to
      design glucocorticoid structures with an increased therapeutic window have
      focused on dissociating anti-inflammatory transcriptional repression from adverse
      effects primarily driven by transcriptional activation. An alternative to this
      medicinal chemistry approach is a systems biology based strategy that seeks to
      amplify selectively the anti-inflammatory activity of very low dose
      glucocorticoid in immune cells without modulating alternative cellular networks
      that mediate glucocorticoid toxicity. METHODS: The combination of prednisolone
      and the antithrombotic drug dipyridamole was profiled using in vitro and in vivo
      models of anti-inflammatory activity and glucocorticoid-induced adverse effects
      to demonstrate a dissociated activity profile. RESULTS: The combination
      synergistically suppresses release of proinflammatory mediators, including tumour
      necrosis factor-alpha, IL-6, chemokine (C-C motif) ligand 5 (RANTES), matrix
      metalloproteinase-9, and others, from human peripheral blood mononuclear cells
      and mouse macrophages. In rat models of acute lipopolysaccharide-induced
      endotoxemia and delayed-type hypersensitivity, and in chronic models of collagen
      induced and adjuvant-induced arthritis, the combination produced anti
      inflammatory activity that required only a subtherapeutic dose of prednisolone.
      The immune-specific amplification of prednisolone anti-inflammatory activity by
      dipyridamole did not extend to glucocorticoid-mediated adverse effects, including
      corticosterone suppression or increased expression of tyrosine aminotransferase,
      in vivo after repeat dosing in rats. After 8 weeks of oral dosing in mice,
      treatment with the combination did not alter prednisolone-induced reduction in
      osteocalcin and mid-femur bone density, which are markers of steroid-induced
      osteoporosis. Additionally, amplification was not observed in the cellular
      network of corticotroph AtT-20/D16v-F2 cells in vitro, as measured by pro
      opiomelanocortin expression and adrenocorticotropic hormone secretion.
      CONCLUSIONS: These data suggest that the multi-target mechanism of low-dose
      prednisolone and dipyridamole creates a dissociated activity profile with an
      increased therapeutic window through cellular network selective amplification of
      glucocorticoid-mediated anti-inflammatory signaling.

PMID- 19171053
TI  - Infection and genotype remodel the entire soybean transcriptome.
AB  - BACKGROUND: High throughput methods, such as high density oligonucleotide
      microarray measurements of mRNA levels, are popular and critical to genome scale
      analysis and systems biology. However understanding the results of these analyses
      and in particular understanding the very wide range of levels of transcriptional
      changes observed is still a significant challenge. Many researchers still use an
      arbitrary cut off such as two-fold in order to identify changes that may be
      biologically significant. We have used a very large-scale microarray experiment
      involving 72 biological replicates to analyze the response of soybean plants to
      infection by the pathogen Phytophthora sojae and to analyze transcriptional
      modulation as a result of genotypic variation. RESULTS: With the unprecedented
      level of statistical sensitivity provided by the high degree of replication, we
      show unambiguously that almost the entire plant genome (97 to 99% of all
      detectable genes) undergoes transcriptional modulation in response to infection
      and genetic variation. The majority of the transcriptional differences are less
      than two-fold in magnitude. We show that low amplitude modulation of gene
      expression (less than two-fold changes) is highly statistically significant and
      consistent across biological replicates, even for modulations of less than 20%.
      Our results are consistent through two different normalization methods and two
      different statistical analysis procedures. CONCLUSION: Our findings demonstrate
      that the entire plant genome undergoes transcriptional modulation in response to
      infection and genetic variation. The pervasive low-magnitude remodeling of the
      transcriptome may be an integral component of physiological adaptation in
      soybean, and in all eukaryotes.

PMID- 19171055
TI  - Generation of a predicted protein database from EST data and application to iTRAQ
      analyses in grape (Vitis vinifera cv. Cabernet Sauvignon) berries at ripening
      initiation.
AB  - BACKGROUND: iTRAQ is a proteomics technique that uses isobaric tags for relative
      and absolute quantitation of tryptic peptides. In proteomics experiments, the
      detection and high confidence annotation of proteins and the significance of
      corresponding expression differences can depend on the quality and the species
      specificity of the tryptic peptide map database used for analysis of the data.
      For species for which finished genome sequence data are not available,
      identification of proteins relies on similarity to proteins from other species
      using comprehensive peptide map databases such as the MSDB. RESULTS: We were
      interested in characterizing ripening initiation ('veraison') in grape berries at
      the protein level in order to better define the molecular control of this
      important process for grape growers and wine makers. We developed a bioinformatic
      pipeline for processing EST data in order to produce a predicted tryptic peptide
      database specifically targeted to the wine grape cultivar, Vitis vinifera cv.
      Cabernet Sauvignon, and lacking truncated N- and C-terminal fragments. By
      searching iTRAQ MS/MS data generated from berry exocarp and mesocarp samples at
      ripening initiation, we determined that implementation of the custom database
      afforded a large improvement in high confidence peptide annotation in comparison
      to the MSDB. We used iTRAQ MS/MS in conjunction with custom peptide db searches
      to quantitatively characterize several important pathway components for berry
      ripening previously described at the transcriptional level and confirmed
      expression patterns for these at the protein level. CONCLUSION: We determined
      that a predicted peptide database for MS/MS applications can be derived from EST
      data using advanced clustering and trimming approaches and successfully
      implemented for quantitative proteome profiling. Quantitative shotgun proteome
      profiling holds great promise for characterizing biological processes such as
      fruit ripening initiation and may be further improved by employing preparative
      techniques and/or analytical equipment that increase peptide detection
      sensitivity via a shotgun approach.

PMID- 19171056
TI  - Automatic versus manual pressure support reduction in the weaning of post
      operative patients: a randomised controlled trial.
AB  - INTRODUCTION: Reduction of automatic pressure support based on a target
      respiratory frequency or mandatory rate ventilation (MRV) is available in the
      Taema-Horus ventilator for the weaning process in the intensive care unit (ICU)
      setting. We hypothesised that MRV is as effective as manual weaning in post
      operative ICU patients. METHODS: There were 106 patients selected in the post
      operative period in a prospective, randomised, controlled protocol. When the
      patients arrived at the ICU after surgery, they were randomly assigned to either:
      traditional weaning, consisting of the manual reduction of pressure support every
      30 minutes, keeping the respiratory rate/tidal volume (RR/TV) below 80 L until 5
      to 7 cmH2O of pressure support ventilation (PSV); or automatic weaning, referring
      to MRV set with a respiratory frequency target of 15 breaths per minute (the
      ventilator automatically decreased the PSV level by 1 cmH2O every four
      respiratory cycles, if the patient's RR was less than 15 per minute). The primary
      endpoint of the study was the duration of the weaning process. Secondary
      endpoints were levels of pressure support, RR, TV (mL), RR/TV, positive end
      expiratory pressure levels, FiO2 and SpO2 required during the weaning process,
      the need for reintubation and the need for non-invasive ventilation in the 48
      hours after extubation. RESULTS: In the intention to treat analysis there were no
      statistically significant differences between the 53 patients selected for each
      group regarding gender (p = 0.541), age (p = 0.585) and type of surgery (p =
      0.172). Nineteen patients presented complications during the trial (4 in the PSV
      manual group and 15 in the MRV automatic group, p < 0.05). Nine patients in the
      automatic group did not adapt to the MRV mode. The mean +/- sd (standard
      deviation) duration of the weaning process was 221 +/- 192 for the manual group,
      and 271 +/- 369 minutes for the automatic group (p = 0.375). PSV levels were
      significantly higher in MRV compared with that of the PSV manual reduction (p <
      0.05). Reintubation was not required in either group. Non-invasive ventilation
      was necessary for two patients, in the manual group after cardiac surgery (p =
      0.51). CONCLUSIONS: The duration of the automatic reduction of pressure support
      was similar to the manual one in the post-operative period in the ICU, but
      presented more complications, especially no adaptation to the MRV algorithm.
      TRIAL REGISTRATION:  TRIAL REGISTRATION NUMBER: ISRCTN37456640.

PMID- 19171058
TI  - Topiramate-associated acute glaucoma in a migraine patient receiving concomitant
      citalopram therapy: a case-report.
AB  - We describe the case of a 34 year-old man with diagnosis of migraine with and
      without aura that developed myopia and acute glaucoma after 7 days of treatment
      with topiramate. The patient had also been taking citalopram daily for two
      months. Both topiramate and citalopram have been related to the increase of
      intraocular pressure and the development of glaucoma. We can't exclude that in
      this patient citalopram caused an increase of the ocular pressure in dose
      dependent manner, facilitating topiramate-induced glaucoma. We recommend to pay
      particular attention in prescribing of topiramate in migraine patients who are
      already under treatment with citalopram or other antidepressants with a similar
      mechanisms of action.

PMID- 19171057
TI  - Quality of care of patients with acute myocardial infarction in Bulgaria: a cross
      sectional study.
AB  - BACKGROUND: Cardiovascular diseases are the major cause of death in Bulgaria.
      Because of notable differences in mortality rates between Bulgaria and other
      European countries, we presume a tangible difference in the management of acute
      myocardial infarction (AMI) and an underutilization of evidence-based treatments.
      In order to determine the quality of care of patients with AMI in Bulgaria, we
      analyzed the appropriateness of current treatments and their relation to patient
      characteristics. METHODS: We performed a descriptive cross-sectional study, using
      retrospectively collected data from medical charts. We included all patients with
      AMI, residing and admitted to hospitals in the region of Stara Zagora, Bulgaria,
      between September 1st and December 31st, 2004. Socioeconomic status was surveyed
      within the framework of a structured patient interview. We used chi-square tests
      with Fisher's exact probabilities to analyze the relationship between prehospital
      time delay age, sex, and socio-economic status of the patients and Student's
      independent samples t-tests to check hypotheses about means. RESULTS: From 134
      patients with AMI (mean age 64.6, SD 13.2, 66% male), 7% presented to a hospital
      within 59 minutes, and 44% within 4 hours of symptoms onset. The use of Heparin
      was 98%. In the first 24 hours, ASS was administrated in 82% and beta-Blockers in
      73% of the cases. At discharge Aspirin, beta-Blockers, Angiotensin Converting
      Enzyme Inhibitors or AR-Blockers and Statins were used in 85%, 79%, 66%, and 43%
      of cases respectively. Intravenous fibrinolysis was applied in 32% of the
      eligible patients with ST-segment elevation. Percutaneous coronary interventions
      were applied in four patients within the first month after AMI. Hospital location
      in relation to a patient's place of residence and manner of transportation to
      hospital did not influence the time delay between the onset of symptoms to the
      start of hospital treatment. In the study region, a relation between time delay
      and both age and education level was observed. CONCLUSION: The actual quality of
      care of patients with AMI in Bulgaria lies far from the evidence-based
      recommendations. Additional research and improvements in health services are
      needed to reduce the burden of cardiovascular disease in Bulgaria.

PMID- 19171054
TI  - New discoveries on the biology and detection of human chorionic gonadotropin.
AB  - Human chorionic gonadotropin (hCG) is a glycoprotein hormone comprising 2
      subunits, alpha and beta joined non covalently. While similar in structure to
      luteinizing hormone (LH), hCG exists in multiple hormonal and non-endocrine
      agents, rather than as a single molecule like LH and the other glycoprotein
      hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit
      of hyperglycosylated hCG. For 88 years regular hCG has been known as a promoter
      of corpus luteal progesterone production, even though this function only explains
      3 weeks of a full gestations production of regular hCG. Research in recent years
      has explained the full gestational production by demonstration of critical
      functions in trophoblast differentiation and in fetal nutrition through
      myometrial spiral artery angiogenesis. While regular hCG is made by fused villous
      syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the
      variant hyperglycosylated hCG. This variant is an autocrine factor, acting on
      extravillous invasive cytotrophoblast cells to initiate and control invasion as
      occurs at implantation of pregnancy and the establishment of hemochorial
      placentation, and malignancy as occurs in invasive hydatidiform mole and
      choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous
      invasive cytotrophoblast cells promoting cell invasion, growth and malignancy.
      Other non-trophoblastic malignancies retro-differentiate and produce a
      hyperglycosylated free beta-subunit of hCG (hCG free beta). This has been shown
      to be an autocrine factor antagonizing apoptosis furthering cancer cell growth
      and malignancy. New applications have been demonstrated for total hCG
      measurements and detection of the 3 hCG variants in pregnancy detection,
      monitoring pregnancy outcome, determining risk for Down syndrome fetus,
      predicting preeclampsia, detecting pituitary hCG, detecting and managing
      gestational trophoblastic diseases, diagnosing quiescent gestational
      trophoblastic disease, diagnosing placental site trophoblastic tumor, managing
      testicular germ cell malignancies, and monitoring other human malignancies. There
      are very few molecules with such wide and varying functions as regular hCG and
      its variants, and very few tests with such a wide spectrum of clinical
      applications as total hCG.

PMID- 19171059
TI  - Performance of two questionnaires to measure treatment adherence in patients with
      Type-2 diabetes.
AB  - BACKGROUND: Most valid methods to measure treatment adherence require time and
      resources, and they are not easily applied in highly demanding Primary Health
      Care Clinics (PHCC). The objective of this study was to determine sensitivity,
      specificity, predictive values, likelihood ratios, and post-test probabilities of
      two novel questionnaires as proxy measurements of treatment adherence in Type-2
      diabetic patients. METHODS: Two questionnaires were developed by a group of
      experts to identify the patient's medical prescription knowledge (knowledge) and
      their attitudes toward treatment adherence (attitudes) as proxy measurements of
      adherence. The questionnaires were completed by patients receiving care in PHCC
      pertaining to the Mexican Institute of Social Security in Aguascalientes
      (Mexico). Pill count was used as gold standard. Participants were selected
      randomly, and their oral hypoglycemic prescriptions were studied. The main
      outcome measures for each questionnaire were sensitivity, specificity, predictive
      values, likelihood ratios, and post-test probabilities, all as an independent
      questionnaire test and in a serial analysis. RESULTS: Adherence prevalence was
      27.0% using pill count. Knowledge questionnaire showed the highest sensitivity
      (68.1%) and negative predictive value (82.2%), the lowest negative likelihood
      ratio (0.58) and post-test probability for a negative result (0.16). Serial
      analysis showed the highest specificity (77.4%) and positive predictive value
      (40.1%) as well as the highest positive likelihood ratio (1.8) and post-test
      probability for a positive result (0.39). CONCLUSION: Medical Prescription
      Knowledge questionnaire showed the best performance as proxy measurement to
      identify non-adherence in type 2 diabetic patients regarding negative predictive
      value, negative likelihood ratio, and post-test probability for a negative
      result. However, Medical Prescription Knowledge questionnaire performance may
      change in contexts with higher adherence prevalence. Therefore, more research is
      needed before using this method in other contexts.

PMID- 19171060
TI  - Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in
      bilharzial bladder cancer.
AB  - BACKGROUND: Clinical characterization of bladder carcinomas is still inadequate
      using the standard clinico-pathological prognostic markers. We assessed the
      correlation between nm23-H1, Rb, EGFR and p53 in relation to the clinical outcome
      of patients with muscle invasive bilharzial bladder cancer (MI-BBC). METHODS:
      nm23-H1, Rb, EGFR and p53 expression was assessed in 59 MI-BBC patients using
      immunohistochemistry and reverse transcription (RT-PCR) and was correlated to the
      standard clinico-pathological prognostic factors, patient's outcome and the
      overall survival (OS) rate. RESULTS: Overexpression of EGFR and p53 proteins was
      detected in 66.1% and 35.6%; respectively. Loss of nm23-H1and Rb proteins was
      detected in 42.4% and 57.6%; respectively. Increased EGFR and loss of nm23-H1 RNA
      were detected in 61.5% and 36.5%; respectively. There was a statistically
      significant correlation between p53 and EGFR overexpression (p < 0.0001), nm23
      loss (protein and RNA), lymph node status (p < 0.0001); between the incidence of
      local recurrence and EGFR RNA overexpression (p= 0.003) as well as between the
      incidence of metastasis and altered Rb expression (p = 0.026), p53 overexpression
      (p < 0.0001) and mutation (p = 0.04). Advanced disease stage correlated
      significantly with increased EGFR (protein and RNA) (p = 0.003 & 0.01), reduced
      nm23-H1 RNA (p = 0.02), altered Rb (p = 0.023), and p53 overexpression (p =
      0.004). OS rates correlated significantly, in univariate analysis, with p53
      overexpression (p = 0.011), increased EGFR (protein and RNA, p = 0.034&0.031),
      nm23-H1 RNA loss (p = 0.021) and aberrations of > or = 2 genes. However,
      multivariate analysis showed that only high EGFR overexpression, metastatic
      recurrence, high tumor grade and the combination of > or = 2 affected markers
      were independent prognostic factors. CONCLUSION: nm23-H1, EGFR and p53 could be
      used as prognostic biomarkers in MI-BBC patients. In addition to the standard
      pathological prognostic factors, a combination of these markers (> or = 2) has
      synergistic effects in stratifying patients into variable risk groups. The higher
      is the number of altered biomarkers, the higher will be the risk of disease
      progression and death.

PMID- 19171061
TI  - Elongation, proliferation & migration differentiate endothelial cell phenotypes
      and determine capillary sprouting.
AB  - BACKGROUND: Angiogenesis, the growth of capillaries from preexisting blood
      vessels, has been extensively studied experimentally over the past thirty years.
      Molecular insights from these studies have lead to therapies for cancer, macular
      degeneration and ischemia. In parallel, mathematical models of angiogenesis have
      helped characterize a broader view of capillary network formation and have
      suggested new directions for experimental pursuit. We developed a computational
      model that bridges the gap between these two perspectives, and addresses a
      remaining question in angiogenic sprouting: how do the processes of endothelial
      cell elongation, migration and proliferation contribute to vessel formation?
      RESULTS: We present a multiscale systems model that closely simulates the
      mechanisms underlying sprouting at the onset of angiogenesis. Designed by agent
      based programming, the model uses logical rules to guide the behavior of
      individual endothelial cells and segments of cells. The activation,
      proliferation, and movement of these cells lead to capillary growth in three
      dimensions. By this means, a novel capillary network emerges out of
      combinatorially complex interactions of single cells. Rules and parameter ranges
      are based on literature data on endothelial cell behavior in vitro. The model is
      designed generally, and will subsequently be applied to represent species
      specific, tissue-specific in vitro and in vivo conditions. Initial results
      predict tip cell activation, stalk cell development and sprout formation as a
      function of local vascular endothelial growth factor concentrations and the Delta
      like 4 Notch ligand, as it might occur in a three-dimensional in vitro setting.
      Results demonstrate the differential effects of ligand concentrations, cell
      movement and proliferation on sprouting and directional persistence. CONCLUSION:
      This systems biology model offers a paradigm closely related to biological
      phenomena and highlights previously unexplored interactions of cell elongation,
      migration and proliferation as a function of ligand concentration, giving insight
      into key cellular mechanisms driving angiogenesis.

PMID- 19171062
TI  - Mechanical compression attenuates normal human bronchial epithelial wound
      healing.
AB  - BACKGROUND: Airway narrowing associated with chronic asthma results in the
      transmission of injurious compressive forces to the bronchial epithelium and
      promotes the release of pro-inflammatory mediators and the denudation of the
      bronchial epithelium. While the individual effects of compression or denudation
      are well characterized, there is no data to elucidate how these cells respond to
      the application of mechanical compression in the presence of a compromised
      epithelial layer. METHODS: Accordingly, differentiated normal human bronchial
      epithelial cells were exposed to one of four conditions: 1) unperturbed control
      cells, 2) single scrape wound only, 3) static compression (6 hours of 30 cmH2O),
      and 4) 6 hours of static compression after a scrape wound. Following treatment,
      wound closure rate was recorded, media was assayed for mediator content and the
      cytoskeletal network was fluorescently labeled. RESULTS: We found that mechanical
      compression and scrape injury increase TGF-beta2 and endothelin-1 secretion,
      while EGF content in the media is attenuated with both injury modes. The
      application of compression after a pre-existing scrape wound augmented these
      observations, and also decreased PGE2 media content. Compression stimulated
      depolymerization of the actin cytoskeleton and significantly attenuated wound
      healing. Closure rate was partially restored with the addition of exogenous PGE2,
      but not EGF. CONCLUSION: Our results suggest that mechanical compression reduces
      the capacity of the bronchial epithelium to close wounds, and is, in part,
      mediated by PGE2 and a compromised cytoskeleton.

PMID- 19171063
TI  - Facile promoter deletion in Escherichia coli in response to leaky expression of
      very robust and benign proteins from common expression vectors.
AB  - BACKGROUND: Overexpression of proteins in Escherichia coli is considered routine
      today, at least when the protein is soluble and not otherwise toxic for the host.
      We report here that the massive overproduction of even such "benign" proteins can
      cause surprisingly efficient promoter deletions in the expression plasmid,
      leading to the growth of only non-producers, when expression is not well
      repressed in the newly transformed bacterial cell. Because deletion is so facile,
      it might impact on high-throughput protein production, e.g. for structural
      genomics, where not every expression parameter will be monitored. RESULTS: We
      studied the high-level expression of several robust non-toxic proteins using a T5
      promoter under lac operator control. Full induction leads to no significant
      growth retardation. We compared expression from almost identical plasmids with or
      without the lacI gene together in strains expressing different levels of LacI.
      Any combination without net overexpression of LacI led to an efficient promoter
      deletion in the plasmid, although the number of growing colonies and even the
      plasmid size - all antibiotic-resistant non-producers - was almost normal, and
      thus the problem not immediately recognizable. However, by assuring sufficient
      repression during the initial establishment phase of the plasmid, deletion was
      completely prevented. CONCLUSION: The deletions in the insufficiently repressed
      system are caused entirely by the burden of high-level translation. Since the E.
      coli Dps protein, known to protect DNA against stress in the stationary phase, is
      accumulated in the deletion mutants, the mutation may have taken place during a
      transient stationary phase. The cause of the deletion is thus distinct from the
      well known interference of high-level transcription with plasmid replication. The
      deletion can be entirely prevented by overexpressing LacI, a useful precaution
      even without any signs of stress caused by the protein.

PMID- 19171064
TI  - Coordinations between gene modules control the operation of plant amino acid
      metabolic networks.
AB  - BACKGROUND: Being sessile organisms, plants should adjust their metabolism to
      dynamic changes in their environment. Such adjustments need particular
      coordination in branched metabolic networks in which a given metabolite can be
      converted into multiple other metabolites via different enzymatic chains. In the
      present report, we developed a novel "Gene Coordination" bioinformatics approach
      and use it to elucidate adjustable transcriptional interactions of two branched
      amino acid metabolic networks in plants in response to environmental stresses,
      using publicly available microarray results. RESULTS: Using our "Gene
      Coordination" approach, we have identified in Arabidopsis plants two oppositely
      regulated groups of "highly coordinated" genes within the branched Asp-family
      network of Arabidopsis plants, which metabolizes the amino acids Lys, Met, Thr,
      Ile and Gly, as well as a single group of "highly coordinated" genes within the
      branched aromatic amino acid metabolic network, which metabolizes the amino acids
      Trp, Phe and Tyr. These genes possess highly coordinated adjustable negative and
      positive expression responses to various stress cues, which apparently regulate
      adjustable metabolic shifts between competing branches of these networks. We also
      provide evidence implying that these highly coordinated genes are central to
      impose intra- and inter-network interactions between the Asp-family and aromatic
      amino acid metabolic networks as well as differential system interactions with
      other growth promoting and stress-associated genome-wide genes. CONCLUSION: Our
      novel Gene Coordination elucidates that branched amino acid metabolic networks in
      plants are regulated by specific groups of highly coordinated genes that possess
      adjustable intra-network, inter-network and genome-wide transcriptional
      interactions. We also hypothesize that such transcriptional interactions enable
      regulatory metabolic adjustments needed for adaptation to the stresses.

PMID- 19171065
TI  - Genome and gene alterations by insertions and deletions in the evolution of human
      and chimpanzee chromosome 22.
AB  - BACKGROUND: Understanding structure and function of human genome requires
      knowledge of genomes of our closest living relatives, the primates. Nucleotide
      insertions and deletions (indels) play a significant role in differentiation that
      underlies phenotypic differences between humans and chimpanzees. In this study,
      we evaluated distribution, evolutionary history, and function of indels found by
      comparing syntenic regions of the human and chimpanzee genomes. RESULTS:
      Specifically, we identified 6,279 indels of 10 bp or greater in a ~33 Mb
      alignment between human and chimpanzee chromosome 22. After the exclusion of
      those in repetitive DNA, 1,429 or 23% of indels still remained. This group was
      characterized according to the local or genome-wide repetitive nature, size,
      location relative to genes, and other genomic features. We defined three major
      classes of these indels, using local structure analysis: (i) those indels found
      uniquely without additional copies of indel sequence in the surrounding (10 Kb)
      region, (ii) those with at least one exact copy found nearby, and (iii) those
      with similar but not identical copies found locally. Among these classes, we
      encountered a high number of exactly repeated indel sequences, most likely due to
      recent duplications. Many of these indels (683 of 1,429) were in proximity of
      known human genes. Coding sequences and splice sites contained significantly
      fewer of these indels than expected from random expectations, suggesting that
      selection is a factor in limiting their persistence. A subset of indels from
      coding regions was experimentally validated and their impacts were predicted
      based on direct sequencing in several human populations as well as chimpanzees,
      bonobos, gorillas, and two subspecies of orangutans. CONCLUSION: Our analysis
      demonstrates that while indels are distributed essentially randomly in intergenic
      and intronic genomic regions, they are significantly under-represented in coding
      sequences. There are substantial differences in representation of indel classes
      among genomic elements, most likely caused by differences in their evolutionary
      histories. Using local sequence context, we predicted origins and phylogenetic
      relationships of gene-impacting indels in primate species. These results suggest
      that genome plasticity is a major force behind speciation events separating the
      great ape lineages.

PMID- 19171066
TI  - Barriers to home care for terminally ill Turkish and Moroccan migrants, perceived
      by GPs and nurses: a survey.
AB  - BACKGROUND: Previous qualitative research proved that relatives of elderly
      terminally ill Turkish and Moroccan immigrants experience several barriers to the
      use of Dutch professional home care. The aim of this study was to explore how
      general practitioners and home care nurses perceive the home care for terminally
      ill Turkish and Moroccan migrants and their families in the Netherlands. METHODS:
      Questionnaires were sent to home care organizations and GPs working in areas
      where most of these migrants are living. 93 nurses and 78 GPs provided
      information about their experiences and opinions regarding home care for this
      group of patients. The data were analyzed by descriptive statistics. RESULTS: GPs
      refer relatively few patients from these migrant groups to home care. They often
      find it difficult to assess the needs of these patients and their families. In
      40% of the GPs' cases in which terminally ill Turkish and Moroccan migrants were
      not referred to home care, the GP regretted this afterwards: the patients had not
      received sufficient qualified care, and their informal carers had often become
      overburdened.In addition, home care nurses often express dissatisfaction with the
      home care given to terminally ill Turkish or Moroccan patients, because of
      communication problems, the patients' lack of knowledge of the disease, or
      difficulties in making suitable appointments with the patient or with the family.
      CONCLUSION: Nurses and GPs cite chiefly similar factors influencing access to and
      use of home care as family members did in a previous study. However, according to
      GPs and nurses, the main barrier to the use of home care concerns communication
      problems, while relatives cited the preference for family care as the main reason
      for abstaining from the use of home care.

PMID- 19171067
TI  - A consensus genetic map of sorghum that integrates multiple component maps and
      high-throughput Diversity Array Technology (DArT) markers.
AB  - BACKGROUND: Sorghum genome mapping based on DNA markers began in the early 1990s
      and numerous genetic linkage maps of sorghum have been published in the last
      decade, based initially on RFLP markers with more recent maps including AFLPs and
      SSRs and very recently, Diversity Array Technology (DArT) markers. It is
      essential to integrate the rapidly growing body of genetic linkage data produced
      through DArT with the multiple genetic linkage maps for sorghum generated through
      other marker technologies. Here, we report on the colinearity of six independent
      sorghum component maps and on the integration of these component maps into a
      single reference resource that contains commonly utilized SSRs, AFLPs, and high
      throughput DArT markers. RESULTS: The six component maps were constructed using
      the MultiPoint software. The lengths of the resulting maps varied between 910 and
      1528 cM. The order of the 498 markers that segregated in more than one population
      was highly consistent between the six individual mapping data sets. The framework
      consensus map was constructed using a "Neighbours" approach and contained 251
      integrated bridge markers on the 10 sorghum chromosomes spanning 1355.4 cM with
      an average density of one marker every 5.4 cM, and were used for the projection
      of the remaining markers. In total, the sorghum consensus map consisted of a
      total of 1997 markers mapped to 2029 unique loci (1190 DArT loci and 839 other
      loci) spanning 1603.5 cM and with an average marker density of 1 marker/0.79 cM.
      In addition, 35 multicopy markers were identified. On average, each chromosome on
      the consensus map contained 203 markers of which 58.6% were DArT markers. Non
      random patterns of DNA marker distribution were observed, with some clear marker
      dense regions and some marker-rare regions. CONCLUSION: The final consensus map
      has allowed us to map a larger number of markers than possible in any individual
      map, to obtain a more complete coverage of the sorghum genome and to fill a
      number of gaps on individual maps. In addition to overall general consistency of
      marker order across individual component maps, good agreement in overall
      distances between common marker pairs across the component maps used in this
      study was determined, using a difference ratio calculation. The obtained
      consensus map can be used as a reference resource for genetic studies in
      different genetic backgrounds, in addition to providing a framework for
      transferring genetic information between different marker technologies and for
      integrating DArT markers with other genomic resources. DArT markers represent an
      affordable, high throughput marker system with great utility in molecular
      breeding programs, especially in crops such as sorghum where SNP arrays are not
      publicly available.

PMID- 19171068
TI  - Trends in hospitalizations for diagnosed congenital cytomegalovirus in infants
      and children in Australia.
AB  - BACKGROUND: Cytomegalovirus (CMV) is responsible for a wide range of diseases in
      neonates, and has been recognized as a major cause of congenital defects in
      developed countries for many years. More children suffer serious disabilities
      caused by congenital CMV than by several better-known childhood maladies. Insight
      into the epidemiology of congenital CMV disease is needed for the assessment of
      preventive strategies. METHODS: Using data from the National Hospital Morbidity
      Database (NHMD) complied by the Australian Institute of Health and Welfare
      (AIHW), we examined the rates of hospital admissions for children diagnosed with
      congenital cytomegalovirus (CMV) by year, sex, age group and length of stay.
      RESULTS: Over an 8-year period (1993-2001), there were 1314 admissions for the
      congenital form of CMV disease. Of these admissions, 25% were principally
      hospitalized because of congenital CMV. The average annual rate of admissions in
      children aged 0-4, 5-9 and 10-14 years was 9.40, 2.40 and 0.85 per 100,000
      Australian population respectively. CONCLUSION: Compared with many other
      congenital illnesses, which are now vaccine preventable, the burden of congenital
      CMV is comparatively high. A vaccination program would be justifiable should a
      vaccine become available.

PMID- 19171069
TI  - Sparse canonical methods for biological data integration: application to a cross
      platform study.
AB  - BACKGROUND: In the context of systems biology, few sparse approaches have been
      proposed so far to integrate several data sets. It is however an important and
      fundamental issue that will be widely encountered in post genomic studies, when
      simultaneously analyzing transcriptomics, proteomics and metabolomics data using
      different platforms, so as to understand the mutual interactions between the
      different data sets. In this high dimensional setting, variable selection is
      crucial to give interpretable results. We focus on a sparse Partial Least Squares
      approach (sPLS) to handle two-block data sets, where the relationship between the
      two types of variables is known to be symmetric. Sparse PLS has been developed
      either for a regression or a canonical correlation framework and includes a built
      in procedure to select variables while integrating data. To illustrate the
      canonical mode approach, we analyzed the NCI60 data sets, where two different
      platforms (cDNA and Affymetrix chips) were used to study the transcriptome of
      sixty cancer cell lines. RESULTS: We compare the results obtained with two other
      sparse or related canonical correlation approaches: CCA with Elastic Net
      penalization (CCA-EN) and Co-Inertia Analysis (CIA). The latter does not include
      a built-in procedure for variable selection and requires a two-step analysis. We
      stress the lack of statistical criteria to evaluate canonical correlation
      methods, which makes biological interpretation absolutely necessary to compare
      the different gene selections. We also propose comprehensive graphical
      representations of both samples and variables to facilitate the interpretation of
      the results. CONCLUSION: sPLS and CCA-EN selected highly relevant genes and
      complementary findings from the two data sets, which enabled a detailed
      understanding of the molecular characteristics of several groups of cell lines.
      These two approaches were found to bring similar results, although they
      highlighted the same phenomenons with a different priority. They outperformed CIA
      that tended to select redundant information.

PMID- 19171070
TI  - Effectiveness and cost-effectiveness of an educational intervention for practice
      teams to deliver problem focused therapy for insomnia: rationale and design of a
      pilot cluster randomised trial.
AB  - BACKGROUND: Sleep problems are common, affecting over a third of adults in the
      United Kingdom and leading to reduced productivity and impaired health-related
      quality of life. Many of those whose lives are affected seek medical help from
      primary care. Drug treatment is ineffective long term. Psychological methods for
      managing sleep problems, including cognitive behavioural therapy for insomnia
      (CBTi) have been shown to be effective and cost effective but have not been
      widely implemented or evaluated in a general practice setting where they are most
      likely to be needed and most appropriately delivered. This paper outlines the
      protocol for a pilot study designed to evaluate the effectiveness and cost
      effectiveness of an educational intervention for general practitioners, primary
      care nurses and other members of the primary care team to deliver problem focused
      therapy to adult patients presenting with sleep problems due to lifestyle causes,
      pain or mild to moderate depression or anxiety. METHODS AND DESIGN: This will be
      a pilot cluster randomised controlled trial of a complex intervention. General
      practices will be randomised to an educational intervention for problem focused
      therapy which includes a consultation approach comprising careful assessment
      (using assessment of secondary causes, sleep diaries and severity) and use of
      modified CBTi for insomnia in the consultation compared with usual care (general
      advice on sleep hygiene and pharmacotherapy with hypnotic drugs). Clinicians
      randomised to the intervention will receive an educational intervention (2 x 2
      hours) to implement a complex intervention of problem focused therapy. Clinicians
      randomised to the control group will receive reinforcement of usual care with
      sleep hygiene advice. Outcomes will be assessed via self-completion
      questionnaires and telephone interviews of patients and staff as well as clinical
      records for interventions and prescribing. DISCUSSION: Previous studies in adults
      have shown that psychological treatments for insomnia administered by specialist
      nurses to groups of patients can be effective within a primary care setting. This
      will be a pilot study to determine whether an educational intervention aimed at
      primary care teams to deliver problem focused therapy for insomnia can improve
      sleep management and outcomes for individual adult patients presenting to general
      practice. The study will also test procedures and collect information in
      preparation for a larger definitive cluster-randomised trial. The study is funded
      by The Health Foundation.

PMID- 19171071
TI  - Enhanced quantal release of excitatory transmitter in anterior cingulate cortex
      of adult mice with chronic pain.
AB  - The anterior cingulate cortex (ACC) is a forebrain structure that plays important
      roles in emotion, learning, memory and persistent pain. Our previous studies have
      demonstrated that the enhancement of excitatory synaptic transmission was induced
      by peripheral inflammation and nerve injury in ACC synapses. However, little
      information is available on their presynaptic mechanisms, since the source of the
      enhanced synaptic transmission could include the enhanced probability of
      neurotransmitter release at existing release sites and/or increases in the number
      of available vesicles. The present study aims to perform quantal analysis of
      excitatory synapses in the ACC with chronic pain to examine the source of these
      increases. The quantal analysis revealed that both probability of transmitter
      release and number of available vesicles were increased in a mouse model of
      peripheral inflammation, whereas only probability of transmitter release but not
      number of available vesicles was enhanced in a mouse model of neuropathic pain.
      In addition, we compared the miniature excitatory postsynaptic potentials
      (mEPSCs) in ACC synapses with those in other pain-related brain areas such as the
      amygdala and spinal cord. Interestingly, the rate and amplitude of mEPSCs in ACC
      synapses were significantly lower than those in the amygdala and spinal cord. Our
      studies provide strong evidences that chronic inflammatory pain increases both
      probability of transmitter release and number of available vesicles, whereas
      neuropathic pain increases only probability of transmitter release in the ACC
      synapses.

PMID- 19171072
TI  - Upregulation of prolylcarboxypeptidase (PRCP) in lipopolysaccharide (LPS) treated
      endothelium promotes inflammation.
AB  - BACKGROUND: Prolylcarboxypeptidase (Prcp) gene, along with altered PRCP and
      kallikrein levels, have been implicated in inflammation pathogenesis. PRCP
      regulates angiotensin 1-7 (Ang 1-7) - and bradykinin (BK) - stimulated nitric
      oxide production in endothelial cells. The mechanism through which kallikrein
      expression is altered during infection is not fully understood. Investigations
      were performed to determine the association between PRCP and kallikrein levels as
      a function of the upregulation of PRCP expression and the link between PRCP and
      inflammation risk in lipopolysaccharide (LPS)-induced endothelium activation.
      METHODS: The Prcp transcript expression in LPS-induced human umbilical vein
      endothelial cells (HUVEC) activation was determined by RT-PCR for mRNA. PRCP
      dependent kallikrein pathway was determined either by Enzyme Linked ImmunoSorbent
      Assay (ELISA) or by biochemical assay. RESULTS: We report that PRCP is critical
      to the maintenance of the endothelial cells, and its upregulation contributes to
      the risk of developing inflammation. Significant elevation in kallikrein was seen
      on LPS-treated HUVECs. The conversion of PK to kallikrein was blocked by the
      inhibitor of PRCP, suggesting that PRCP might be a risk factor for inflammation.
      CONCLUSION: The increased PRCP lead to a sustained production of bradykinin in
      endothelium following LPS treatment. This amplification may be an additional
      mechanism whereby PRCP promotes a sustained inflammatory response. A better
      appreciation of the role of PRCP in endothelium may contribute to a better
      understanding of inflammatory vascular disorders and to the development of a
      novel treatment.

PMID- 19171073
TI  - Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with
      low levels of apoptosis in active rheumatoid synovium.
AB  - INTRODUCTION: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is
      a tumour necrosis factor (TNF) family member capable of inducing apoptosis in
      many cell types. METHODS: Using immunohistochemistry, terminal deoxynucleotidyl
      transferase biotin-dUTP nick end labelling (TUNEL) and real-time PCR we
      investigated the expression of TRAIL, TRAIL receptors and several key molecules
      of the intracellular apoptotic pathway in human synovial tissues from various
      types of arthritis and normal controls. Synovial tissues from patients with
      active rheumatoid arthritis (RA), inactive RA, osteoarthritis (OA) or
      spondyloarthritis (SpA) and normal individuals were studied. RESULTS:
      Significantly higher levels of TRAIL, TRAIL R1, TRAIL R2 and TRAIL R4 were
      observed in synovial tissues from patients with active RA compared with normal
      controls (p < 0.05). TRAIL, TRAIL R1 and TRAIL R4 were expressed by many of the
      cells expressing CD68 (macrophages). Lower levels of TUNEL but higher levels of
      cleaved caspase-3 staining were detected in tissue from active RA compared with
      inactive RA patients (p < 0.05). Higher levels of survivin and x-linked inhibitor
      of apoptosis protein (xIAP) were expressed in active RA synovial tissues compared
      with inactive RA observed at both the protein and mRNA levels. CONCLUSIONS: This
      study indicates that the induction of apoptosis in active RA synovial tissues is
      inhibited despite stimulation of the intracellular pathway(s) that lead to
      apoptosis. This inhibition of apoptosis was observed downstream of caspase-3 and
      may involve the caspase-3 inhibitors, survivin and xIAP.

PMID- 19171074
TI  - Early and very early hepatocellular carcinoma: when and how much do staging and
      choice of treatment really matter? A multi-center study.
AB  - BACKGROUND: A consensus on the most reliable staging system for hepatocellular
      carcinoma (HCC) is still lacking but the most used is a revised Barcelona Clinic
      Liver Cancer (BCLC) system, adopted by the American Association for the Study of
      Liver Diseases (AASLD). We investigated how many patients are diagnosed in "very
      early" and "early" stage, follow the AASLD guidelines for treatment and whether
      their survival depends on treatment. METHODS: Data were collected in 530 "very
      early" and "early" HCC patients recruited by a multicentric Italian collaborative
      group (ITA.LI.CA). The Kaplan-Meier method was used to estimate overall survival
      and the log rank to test the statistical significance of difference between
      groups. Cox's multivariate stepwise regression analysis was used to pinpoint
      independent prognostic factors and the adjusted relative risks (hazard ratios)
      were calculated as well. A statistical analysis based on the chi-square test was
      used to identify significant differences in clinical or pathological features
      between patients. A P-value < 0.05 was considered statistically significant.
      RESULTS: "Very early" HCC were 3%; Cox multivariate analysis did not identify
      variables independently associated with survival. The patients following AASLD
      recommendations (20%) did not show longer survival. In "early" HCC patients
      (25%), treatment significantly modulated survival (p = 0.0001); the 28% patients
      treated according to the AASLD criteria survived longer (p = 0,004). The Cox
      analysis however identified only age, gender, number of lesions and Child class
      as independent predictors of survival. CONCLUSION: patients with very early" HCC
      were very few in this analysis. In most instances they were not treated with the
      treatment suggested as the most appropriate by the AASLD guidelines and the type
      of treatment had no impact on survival, even though the number of patients was
      relatively low and part of the patients were diagnosed before the introduction of
      the guidelines: this analysis, therefore, might not be considered as conclusive
      and should be validated. The "early" stage group involved more patients, rarely
      treated according to the guidelines, both overall and also in those diagnosed
      after their publication; the survival was in part predicted by the type of
      treatment, with better results in those treated according to AASLD indications.

PMID- 19171075
TI  - Analysis of research output parameters: density equalizing mapping and citation
      trend analysis.
AB  - BACKGROUND: Burden of disease studies indicate major socio-economic burdens since
      many years. They should be used for the allocation of funding. However,
      imbalances are present in funding policies and therefore benchmarking becomes
      increasingly important in health services research. METHODS: The present study
      assessed benchmarking approaches. Using large data base analyses, research was
      analyzed for different health research output parameters. The fields of
      cardiovascular and respiratory medicine served as models to assess irregular
      patterns of health research. For visualization, density equalizing mapping
      procedures were used. RESULTS: Specific areas of major research activity were
      identified for European countries and large differences were found. Spatial
      distribution of published items for cardiac and cardiovascular systems differed
      in comparison to the distribution for the respiratory system. In general, large
      countries dominated the overall number of published items. When qualitative
      measures such as citation analysis were assessed, differing results were
      achieved. In this category, mostly Scandinavian countries dominated. CONCLUSION:
      The present approach of comparative output benchmarking can be used to assess
      institutional operating figures at the national and international level and to
      analyze imbalances in health and research funding.

PMID- 19171077
TI  - Differential frontal-striatal and paralimbic activity during reversal learning in
      major depressive disorder and obsessive-compulsive disorder.
AB  - BACKGROUND: Several lines of research suggest a disturbance of reversal learning
      (reward and punishment processing, and affective switching) in patients with
      major depressive disorder (MDD). Obsessive-compulsive disorder (OCD) is also
      characterized by abnormal reversal learning, and is often co-morbid with MDD.
      However, neurobiological distinctions between the disorders are unclear.
      Functional neuroimaging (activation) studies comparing MDD and OCD directly are
      lacking. METHOD: Twenty non-medicated OCD-free patients with MDD, 20 non
      medicated MDD-free patients with OCD, and 27 healthy controls performed a self
      paced reversal learning task in an event-related design during functional
      magnetic resonance imaging (fMRI). RESULTS: Compared with healthy controls, both
      MDD and OCD patients displayed prolonged mean reaction times (RTs) but normal
      accuracy. In MDD subjects, mean RTs were correlated with disease severity.
      Imaging results showed MDD-specific hyperactivity in the anterior insula during
      punishment processing and in the putamen during reward processing. Moreover,
      blood oxygen level-dependent (BOLD) responses in the dorsolateral prefrontal
      cortex (DLPFC) and the anterior PFC during affective switching showed a linear
      decrease across controls, MDD and OCD. Finally, the OCD group showed blunted
      responsiveness of the orbitofrontal (OFC)-striatal loop during reward, and in the
      OFC and anterior insula during affective switching. CONCLUSIONS: This study shows
      frontal-striatal and (para)limbic functional abnormalities during reversal
      learning in MDD, in the context of generic psychomotor slowing. These data
      converge with currently influential models on the neuropathophysiology of MDD.
      Moreover, this study reports differential neural patterns in frontal-striatal and
      paralimbic structures on this task between MDD and OCD, confirming previous
      findings regarding the neural correlates of deficient reversal learning in OCD.

PMID- 19171076
TI  - A circuit supporting concentration-invariant odor perception in Drosophila.
AB  - BACKGROUND: Most odors are perceived to have the same quality over a large
      concentration range, but the neural mechanisms that permit concentration
      invariant olfactory perception are unknown. In larvae of the vinegar fly
      Drosophila melanogaster, odors are sensed by an array of 25 odorant receptors
      expressed in 21 olfactory sensory neurons (OSNs). We investigated how subsets of
      larval OSNs with overlapping but distinct response properties cooperate to
      mediate perception of a given odorant across a range of concentrations. RESULTS:
      Using calcium imaging, we found that ethyl butyrate, an ester perceived by humans
      as fruity, activated three OSNs with response thresholds that varied across three
      orders of magnitude. Whereas wild-type larvae were strongly attracted by this
      odor across a 500-fold range of concentration, individuals with only a single
      functional OSN showed attraction across a narrower concentration range
      corresponding to the sensitivity of each ethyl butyrate-tuned OSN. To clarify how
      the information carried by different OSNs is integrated by the olfactory system,
      we characterized the response properties of local inhibitory interneurons and
      projection neurons in the antennal lobe. Local interneurons only responded to
      high ethyl butyrate concentrations upon summed activation of at least two OSNs.
      Projection neurons showed a reduced response to odors when summed input from two
      OSNs impinged on the circuit compared to when there was only a single functional
      OSN. CONCLUSIONS: Our results show that increasing odor concentrations induce
      progressive activation of concentration-tuned olfactory sensory neurons and
      concomitant recruitment of inhibitory local interneurons. We propose that the
      interplay of combinatorial OSN input and local interneuron activation allows
      animals to remain sensitive to odors across a large range of stimulus
      intensities.

PMID- 19171078
TI  - Effects of induced anger in patients with antisocial personality disorder.
AB  - BACKGROUND: Anger is the main deregulated emotion in patients with antisocial
      personality disorder (ASPD). The aim of this study was to examine emotional,
      cognitive and physiological correlates of anger and compare these between ASPD
      patients with varying degree of psychopathy (PP) and control groups. METHOD:
      Assessment of the effect of anger induction on self-reported emotions and schema
      modes, psychophysiology and implicit reaction-time tasks measuring self-anger and
      aggressor-swearword associations. Participants (n=147) were patients with DSM-IV
      antisocial (n=21), borderline (n=45) and cluster C personality disorder (n=46)
      and non-patient controls (n=35). RESULTS: Groups did not differ in self-reported
      anger. ASPD patients displayed a decrease in heart rate and systolic blood
      pressure (SBP) and stronger implicit self-anger associations. ASPD patients
      scoring low on affective PP reported less negative emotions and displayed a
      greater decrease in diastolic blood pressure (DBP). CONCLUSIONS: ASPD patients
      did not display a deviant self-reported anger but physiological hyporesponsivity
      and cognitive hyper-responsivity. This ASPD anger response might reflect a
      controlled predatory-like fight preparation.

PMID- 19171079
TI  - An international comparison of adolescent non-suicidal self-injury (NSSI) and
      suicide attempts: Germany and the USA.
AB  - BACKGROUND: This study examined the prevalence of non-suicidal self-injury
      (NSSI), suicide attempts, suicide threats and suicidal ideation in a German
      school sample and compared the rates with a similar sample of adolescents from
      the midwestern USA by using cross-nationally validated assessment tools. METHOD:
      Data were provided from 665 adolescents (mean age 14.8 years, S.D.=0.66, range 14
      17 years) in a school setting. Students completed the Self-Harm Behavior
      Questionnaire (SHBQ), the Ottawa Self-Injury Inventory (OSI) and a German version
      of the Center for Epidemiological Studies-Depression Scale (CES-D). RESULTS: A
      quarter of the participants (25.6%) endorsed at least one act of NSSI in their
      life, and 9.5% of those students answered that they had hurt themselves
      repetitively (more than four times). Forty-three (6.5%) of the students reported
      a history of a suicide attempt. No statistically significant differences were
      observed between the German and US samples in terms of self-injury or suicidal
      behaviors. CONCLUSIONS: By using the same validated assessment tools, no
      differences were found in the prevalence and characteristics of self-injury and
      suicidal behaviors between adolescents from Germany and the USA. Thus, it seems
      that NSSI has to be understood as worldwide phenomenon, at least in Western
      cultures.

PMID- 19171080
TI  - Two sequential outbreaks in two villages illustrate the various modes of
      transmission of cholera.
AB  - We investigated two sequential outbreaks of severe diarrhoea in two neighbouring
      villages of Orissa, in 2005. We conducted descriptive and matched case-control
      studies. The attack rates were 5.6% (n=62) and 5.2% (n=51), respectively, in the
      first and second villages. One death was reported in the second village (case
      fatality 2%). We identified that consumption of milk products prepared in the
      household of the index case [matched odds ratio (mOR) 5.7, 95% confidence
      interval (CI) 1.7-30] in the first village, and drinking well water in the second
      village were associated with the illness (mOR 4.7, 95% CI 1.6-19). We isolated
      Vibrio cholerae El Tor O1 Ogawa from stool samples from both the villages.
      Mishandling of milk products led to a cholera outbreak in the first village,
      which led to sewerage contamination of a well and another outbreak in the second
      village. Environmental contamination should be expected and prevented during
      cholera outbreaks.

PMID- 19171081
TI  - An alphavirus replicon-derived candidate vaccine against Rift Valley fever virus.
AB  - Rift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus (genus
      Phlebovirus) associated with severe disease in livestock and fatal encephalitis
      or haemorrhagic fever in a proportion of infected humans. Although live
      attenuated and inactivated vaccines have been used in livestock, and on a limited
      scale in humans, there is a need for improved anti-RVFV vaccines. Towards this
      goal, Sindbis virus replicon vectors expressing the RVFV Gn and Gc glycoproteins,
      as well as the non-structural nsM protein, were constructed and evaluated for
      their ability to induce protective immune responses against RVFV. These replicon
      vectors were shown to produce the RVFV glycoproteins to high levels in vitro and
      to induce systemic anti-RVFV antibody responses in immunized mice, as determined
      by RVFV-specific ELISA, fluorescent antibody tests, and demonstration of a
      neutralizing antibody response. Replicon vaccination also provided 100%
      protection against lethal RVFV challenge by either the intraperitoneal or
      intranasal route. Furthermore, preliminary results indicate that the replicon
      vectors elicit RVFV-specific neutralizing antibody responses in vaccinated sheep.
      These results suggest that alphavirus-based replicon vectors can induce
      protective immunity against RVFV, and that this approach merits further
      investigation into its potential utility as a RVFV vaccine.

PMID- 19171082
TI  - The protection motivation theory within the stages of the transtheoretical model 
      stage-specific interplay of variables and prediction of exercise stage
      transitions.
AB  - OBJECTIVE: Two different theories of health behaviour have been chosen with the
      aim of theory integration: a continuous theory (protection motivation theory,
      PMT) and a stage model (transtheoretical model, TTM). This is the first study to
      test whether the stages of the TTM moderate the interrelation of PMT-variables
      and the mediation of motivation, as well as PMT-variables' interactions in
      predicting stage transitions. DESIGN: Hypotheses were tested regarding (1) mean
      patterns, stage pair-comparisons and nonlinear trends using ANOVAs; (2)
      prediction-patterns for the different stage groups employing multi-group
      structural equation modelling (MSEM) and nested model analyses; and (3) stage
      transitions using binary logistic regression analyses. METHOD: Adults (N=1,602)
      were assessed over a 6 month period on their physical activity stages, PMT
      variables and subsequent behaviour. RESULTS: (1) Particular mean differences and
      nonlinear trends in all test variables were found. (2) The PMT adequately fitted
      the five stage groups. The MSEM revealed that covariances within threat appraisal
      and coping appraisal were invariant and all other constrains were stage-specific,
      i.e. stage was a moderator. Except for self-efficacy, motivation fully mediated
      the relationship between the social-cognitive variables and behaviour. (3)
      Predicting stage transitions with the PMT-variables underscored the importance of
      self-efficacy. Only when threat appraisal and coping appraisal were high, stage
      movement was more likely in the preparation stage. CONCLUSIONS: Results emphasize
      stage-specific differences of the PMT mechanisms, and hence, support the stage
      construct. The findings may guide further theory building and research
      integrating different theoretical approaches.

PMID- 19171083
TI  - Psychological processing of transplantation in lung recipients: a quantitative
      study of organ integration and the relationship to the donor.
AB  - OBJECTIVES: Lung recipients undergo a complex psychological process, including
      organ integration and processing of attitudes towards the organ donor. DESIGN:
      Seventy-six lung recipients were asked to participate in a cross-sectional
      questionnaire study on the psychological processing of lung transplants. METHODS:
      The questionnaire consisted of statements describing aspects of organ integration
      and the patient's relationship with the donor. Furthermore, chronic
      stress/psychological distress (Screening Scale of the Trier Inventory; Symptom
      Checklist SCL-K-9) and the emotional effects of transplantation/immunosuppression
      (Transplant Effects Questionnaire; Medication Experience Scale for
      Immunosuppressants) were assessed. RESULTS: In general, lung recipients perceive
      the transplant as part of themselves (97.4%) and not as a foreign object (90%).
      One-third of patients still have frequent thoughts about the donor, whilst the
      majority (80.3%) do not believe that they have adopted the donor's characteristic
      traits. Factor analysis reveals the two-dimensional structure of the
      questionnaire items 'organ integration' (factor 1) and 'relationship to the
      donor' (factor 2). Poor organ integration predicts low adherence, low disclosure
      and high feelings of guilt, whilst a close donor relationship predicts chronic
      stress and psychological distress. CONCLUSIONS: Poor organ integration and a
      close relationship to the donor should be borne in mind in psychosocial treatment
      regarding the patient's adherence behaviour and psychological distress.

PMID- 19171084
TI  - Trait anxiety as an independent predictor of poor health-related quality of life
      and post-traumatic stress symptoms in rectal cancer.
AB  - OBJECTIVES: To determine the influence of trait anxiety on patient reports of
      health-related quality of life (HRQoL) and post-traumatic stress symptoms (PTSS)
      in a sample of rectal cancer survivors. DESIGN: Eighty patients who had been
      diagnosed with rectal cancer were assessed at two points in time in a
      longitudinal study. METHODS: At Time 1, soon after initial treatment,
      participants completed the State-Trait Anxiety Inventory and the Temperament and
      Character Inventory Harm Avoidance scale, which were combined into a composite
      measure of trait anxiety. At Time 2, 2-5 years following Time 1, participants
      were assessed for HRQoL using the Functional Assessment of Cancer Therapy
      Colorectal scale (FACT-C) and for PTSS using the Impact of Event Scale-Revised
      (IES-R). RESULTS: HRQoL and PTSS were generally favourable on average, although
      many of the patients reported faring poorly. Higher levels of trait anxiety were
      predictive of poorer scores on all of the FACT-C and the IES-R total and subscale
      measures. More severe faecal incontinence was associated with poorer scores on
      the FACT Emotional well-being subscale, the FACT-Colorectal Cancer Scale, and all
      of the IES-R scales. Males were more likely than females to have poorer scores on
      the FACT Social well-being subscale, and those patients who were further out from
      active treatment had more favourable scores on the FACT-Colorectal Cancer Scale.
      The presence of a colostomy did not impact HRQoL or PTSS. CONCLUSION: Trait
      anxiety had a significant influence on HRQoL and PTSS several years following
      diagnosis and treatment of rectal cancer.

PMID- 19171085
TI  - Development of an early memories of warmth and safeness scale and its
      relationship to psychopathology.
AB  - Experiences of early childhood have a major impact on physiological,
      psychological, and social aspects of maturation and functioning. One avenue of
      work explores the recall and memory of positive or negative rearing experiences
      and their association with psychopathology measures. However, while many self
      report studies have focused on the recall of parental behaviours this study
      developed a new measure called the early memories of warmth and safeness scale
      (EMWSS), which focuses on recall of one's own inner positive feelings, emotions
      and experiences in childhood. Student participants (N = 180) completed the new
      scale and a series of self-report scales measuring different types of early
      recall, psychopathology, types of positive affect, and self
      criticism/reassurance. The EMWSS was found to have good psychometric properties
      and reliability. Recall of parental behaviour and recall of positive emotional
      memories were highly related, but recall of positive emotional memories was a
      better predictor of psychopathology, styles of self-criticism/self-reassurance
      and disposition to experience positive affect, than recall of parental behaviour.

PMID- 19171087
TI  - [Linkage location and mutation analysis of generalized epilepsy with febrile
      seizures plus].
AB  - OBJECTIVE: To study the etiologic genes of generalized epilepsy with febrile
      seizure plus (GEFS+). METHODS: Peripheral blood samples were collected from 25
      persons of 2 families, including 2 probands. DNA was extracted from the
      peripheral blood leukocytes using phenol-chloroform method. Ten microsatellite
      markers spanning the critical regions of SCN1B, SCN1A, SCN2A, and GABRG2 genes
      were genotyped for linkage analysis by the software LINKAGE v5.1. The two-point
      linkage relation was determined by LOD score defining the approximate position of
      etiologic genes of the 2 GEFS+ families. Mutation analysis of the candidate
      etiologic genes in all members of these 2 families was performed. Results No
      sharing allele was discovered among the several microsatellite markers flanking
      SCN1A, SCN2A, and SCN1B genes, and the involvement of these genes in these 2
      families could be excluded. In the family named Tian, sharing alleles were
      discovered among the markers D5S820, D5S422, and D5S1403 flanking GABRG2 gene.
      The two-point LOD scores at theta = 0 were 0.67, 1.0, and 0.79 for the marker
      D5S820, D5S422, and D5S1403, thus indicating possible linkage. In the family
      named Di, sharing allele was discovered only in the marker D5S1403 flanking the
      GABRG2 gene. Sequence analysis was performed for nine exons of the GABRG2 gene in
      these 2 families. Three single nucleotide variations were discovered on the exon
      5 (c.588 C > T), exon 3 (c.604 C > T), and noncoding region of the exon 7. No
      mutation change of the GABRG2 gene was observed in these 2 families. CONCLUSION:
      No evidence supports the causal relation between the SCN1B, SCN1A, SCN2A, and
      GABRG2 mutation and the etiologic genes in the two families with GEFS+. It is
      still not clear what is the common etiologic genes of GEFS+.

PMID- 19171088
TI  - [Neo-adjuvant chemoradiotherapy followed by surgery in treatment of advanced
      esophageal carcinoma].
AB  - OBJECTIVE: To investigate the effects of neo-adjuvant chemoradiotherapy followed
      by surgery in treatment of advanced esophageal carcinoma. METHODS: Forty-two
      consecutive patients with locally advanced esophageal carcinoma underwent
      chemotherapy and radiotherapy concurrently. The chemotherapy consisted of
      intravenous infusion of vinorelbine (25 mg/m(2) per day) on days 1, 8, 22, and 29
      or 5-fluorouracil (2.4 g/m(2)) on days 1 - 3 and days 22 - 24, and cisplatin (75
      mg/m(2)) on days 1 and 22. Radiotherapy was delivered 5 days a week for 4 weeks
      with the total dose of 40 Gy divided into a daily fraction of 2.0 Gy. After the
      completion of chemoradiotherapy, clinical restaging was performed. Esophagectomy
      and lymphadenectomy were performed 4 - 6 weeks after the chemoradiotherapy.
      RESULTS: Forty-one of the 42 patients finished the preoperative
      chemoradiotherapy. The clinical response rate of chemoradiotherapy was 83.3%.
      Forty cases received esophagectomy, with a radical operation rate of 97.5% and a
      pathological complete response rate of 23.8%. The overall 1, 3, and 5-year
      survival rates were 66.9%, 54.5%, and 44.9% respectively with a median survival
      time of 43.4 months. The 1, 3, and 5-year disease-free survival rates were 61.1%,
      48.7%, and 39.5% respectively with a median disease-free survival time of 32.7
      months. The toxic responses of the chemoradiotherapy, such as myelotoxicity,
      pulmonary toxicity, and esophagitis were at grade 1 or 2. No death occurred
      during chemoradiotherapy. The incidence rates of postoperative pulmonary
      infection and severe arrhythmia were 22.5% and 20.0% respectively. The
      postoperative mortality rate was 5.0%. CONCLUSION: The neoadjuvant
      chemoradiotherapy followed by surgery achieves a high clinical response rate and
      pathologic complete tumor regression rate, significantly downstages the
      esophageal cancer, and improves the survival. Although the toxicity of
      chemoradiotherapy is mild, the side-effects cannot be ignored still.

PMID- 19171089
TI  - [The best concentration ratio of propofol controlled-infusion combined with
      sevoflurane in anesthesia for patients undergoing laparoscopy].
AB  - OBJECTIVE: To investigate the best concentration ratio of propofol controlled
      infusion combined with sevoflurane in anesthesia for patients undergoing
      laparoscopy. METHODS: One hundred patients undergoing cholecystectomy under
      laparoscopy were randomly divided into 5 equal groups treated with propofol
      controlled plasma at the concentrations of 1, 2, 3, 4, and 5 microg/ml
      respectively (Group 1-5). Bispectral index (BIS) was maintained at a range of 50
      +/- 5 by adjusting sevoflurane inhalation. The end-tidal concentration of
      sevoflurane (ETsevo), systolic pressure, diastolic pressure, recovery time,
      awareness, and post-operative nausea and vomiting (PONV) within 24 h after
      operation were recorded. The best concentration ratio of propofol controlled
      infusion combined with sevoflurane with the definition as the highest ETsevo
      without PONV decrease along with the increase of propofol concentration. RESULTS:
      ETsevo was negatively correlated with and propofol concentration. There were nit
      significant differences in the systolic pressure, diastolic pressure, and
      recovery time among different groups. No incidence of intra-operative awareness
      was found. The PONV rates of Group 1 and 2 were both 60%, significantly higher
      than those of the other 3 groups (all P < 0.05) without significant differences
      in PONV rate among Group 3 - 5. The best concentration ratio of propofol
      controlled-infusion combined with sevoflurane was propofol controlled-infusion at
      the concentration of 1 microg/ml with ETsevo at the concentration as 1 minimal
      alveolar concentration (MAC). CONCLUSION: Propofol controlled-infusion at the
      concentration of 1 microg/ml with ETsevo at the concentration as 1 MAC is the
      best concentration ratio with low PONV rate and a possibility to prevent intra
      operative awareness.

PMID- 19171090
TI  - [The role of CD4+ CD25+ T cells in the mechanism of myasthenia gravis in children
      and adults].
AB  - OBJECTIVE: To investigate the role of CD4+CD25+ regulatory T cells in the
      mechanism of myasthenia gravis (MG) in children and adults. METHODS: Peripheral
      blood samples were collected from 13 MG patients, 5 being aged > 14 and 8 being
      aged <or= 14, and 10 age-matched healthy persons. Peripheral blood mononuclear
      cells were isolated. Flow cytometry was used to examine the rate of CD4+CD25+
      regulatory T cells (Tregs). Fluorescence-activated cell sorter was used to detect
      the expression of Foxp3 and CTLA-4, 2 important functional markers of CD4+CD25+
      Tregs. RESULTS: The percentage of CD4+CD25+ Tregs of the MG children was
      significantly higher than that of the healthy children (P < 0.05), and the
      percentage of CD4+CD25+ Tregs of the MG adults was higher then that of the
      healthy adults, but not significantly (P = 0.795). The expression level of Foxp3
      of the MG children was significantly lower than that of the healthy children (P =
      0.011), and the expression level of Foxp3 of the MG adults was not significantly
      different from that of the healthy adult controls (P = 0.084). The expression
      levels of CTLA-4 of both the MG children and adults were lower than those of the
      healthy children and adults, but not significantly (P = 0.556, P = 0.767).
      CONCLUSION: The CD4+CD25+ Tregs in peripheral blood from MG pediatric patients
      are increased in number but unable functionally. The pathogenesis of MG in
      children may be correlated with the impairment of immunotolerance of the
      peripheral blood Tregs.

PMID- 19171091
TI  - [Effects of laparoscopic Burch colposuspension and tension-free vaginal tape in
      treatment of female stress urinary incontinence: a comparative study].
AB  - OBJECTIVE: To evaluate the efficacy and complications of laparoscopic Burch
      colposuspension and tension-free vaginal tape (TVT) in treatment of female stress
      urinary incontinence (SUI). METHODS: Thirty patients underwent laparoscopic Burch
      colposuspension and 67 age, BMI, parity, and grading-matched patients underwent
      TVT because of moderate to severe hypermotility urodynamic SUI from 2002 to 2006.
      Follow-up was conducted for (9 +/- 10) months. The clinical characteristics, mean
      operation time, hospital stay, peri-operative complications, and late
      complications were compared. RESULTS: The mean operative time and the hospital
      stay of the TVT group was (29.57 +/- 8.23) min and (3.0 +/- 2.1) d, both
      significantly shorter than those of the Burch operation group [(87 +/- 23) min
      and (4.8 +/- 1.9) d respectively, P < 0.001 and P < 0.01]. The blood loss of the
      TVT group was (27 +/- 12) ml, significantly less than that of the Burch operation
      group [(59 +/- 30) ml, P < 0.001]. The subjective cure rate of the Burch
      operation group was 86.5%, not significantly different from that of the TVT group
      (95.5%, P > 0.05). Short-term complications included 1 case of bladder injury and
      1 case of circumflex iliac vein injuring, both occurring in the Burch
      colposuspension group. The postoperative urine retention rate of the Burch
      colposuspension group was 23.5%, not significantly different from that of the TVT
      group (14.9%, P > 0.05), and the postoperative fever rate of the Burch
      colposuspension group was 16.2%, significantly higher than that of the TVT group
      (4.5%, P < 0.05). Three cases of erosion of sling were found in the TVT group as
      late complications. CONCLUSION: Both Burch colposuspension and TVT are effective
      in the treatment of female SUI. The mean operative time of Burch operation and
      the hospital stay thereafter are longer; however, the cost of TVT is much higher
      than that of the Burch operation.

PMID- 19171092
TI  - [Sonographic evaluation of the special thyroid carcinoma].
AB  - OBJECTIVE: To analyze the cases of thyroid carcinoma with special sonographic
      features, so as to increase the accuracy of sonographic diagnosis for thyroid
      carcinoma. METHODS: The sonographic characteristics of 9 patients with special
      sonographic appearance were analyzed. According to the sonographic features, they
      were divided into two kinds: 8 cases suffered from thyroid diffuse malignant
      lesions, and one case showed cystic lesion sticking out of the thyroid. The
      sonographic appearance of gray scale and color Doppler characteristics of the
      lesions were recorded. RESULT: In the first kind of lesions, the dimensional
      ultrasound appearance of gray scale had an apparent feature, however, its color
      Doppler characteristics had no apparent feature, and all of the 8 cases were
      diagnosed correctly by ultrasound. In the second kind of lesion, the sonographic
      appearance of gray scale and color Doppler had no special features, so the case
      was diagnosed as benign disease wrongly by ultrasound. CONCLUSION: The first kind
      of lesions has apparent sonographic features, sonographic diagnosis can serve as
      the first choice. However, the second kind of lesion had no apparent sonographic
      feature.

PMID- 19171093
TI  - [Radiological evaluation of peripheral primitive neuroectodermal tumor arising in
      abdomen-pelvis region].
AB  - OBJECTIVE: To analyze the CT and MRI features of peripheral primitive
      neuroectodermal tumor (pPNET) arising in abdomen-pelvis region, and to improve
      the radiological diagnostic ability of this tumor. METHODS: The CT and MRI
      appearances of thirteen abdomen-pelvis region pPNET patients proved
      pathologically were reviewed retrospectively. RESULTS: The age of diagnosis
      ranged from 2 years to 72 years (median, 30 years). The tumors were located in
      the abdomen and pelvic cavity (nine patients), retroperitoneal tissues (two
      patients), right kidney (one patient) and liver (one patient). The radiological
      appearances of the tumors resembled heterogeneous soft tissue masses, eight
      masses with cystic or necrotic areas. Masses in abdomen and pelvic cavity and
      kidney were well-defined; while masses in retroperitoneal tissue and liver were
      ill-defined. Heterogeneous enhancement with intravenous contrast agents was
      evident. There are speckled, patching and irregular calcifications in four
      patients, one of them with calcification after treatment. Five patients died, and
      eight patients remiss on clinical follow-up. CONCLUSIONS: The radiological
      features of peripheral PNET are non-specific. CT and MRI are useful in
      delineating the extent, finding distant metastasis, predicting respectability and
      monitoring treatment.

PMID- 19171094
TI  - [Simulated uterus microenvironment induced human placental mesenchymal stem cells
      differentiation to uterus smooth muscle cells in vitro].
AB  - OBJECTIVE: To develop a new method to promote the differentiation of mesenchymal
      stem cells derived from human placenta (pMSC) to uterus smooth muscle cells
      (uSMC) in simulated uterus microenvironment. METHODS: MSCs were isolated from
      human placenta, cultivated, and analyzed for their phenotype by flow cytometry.
      The multipotential differentiation of the pMSC was examined by chondrogenic,
      adipogenic, and osteogenetic induction. uSMC were isolated from uteri resected
      during operation and co-cultivated with the pMSC in a Transwell chamber
      simulating Two, 4, and 8 days later RT-PCR and Western blotting were used to
      detect the mRNA and protein expression of alpha-actin, calmodulin, and myosin
      heavy chains (MHC), the markers of smooth muscle differentiation at the early,
      middle, and late stages. On day 8 RT-PCR was used to detect the expression of
      estrogen receptor in these 2 groups of cells, then estrogen was used to stimulate
      these cells and the protein kinase C (PKC) activity was examined. RESULTS: The
      pMSC could be induced into adipocytes, osteocytes, and chondrocytes respectively.
      After co-culture with uSMC, the morphology of the pMSC changed closely into that
      of the uSMC, and MHC was expressed in the pMSC. Estrogen receptor was positive in
      both groups of cells. The PKC activity increased, especially in the cell
      membrane, after stimulation of estrogen. CONCLUSION: The postpartum human
      placenta can be used as an important and novel source of multipotent stem cells
      for tissue engineering and genetic engineering. Placental MSC have the potential
      to differentiate into smooth muscle cells under the simulated uterus
      microenvironment in vitro.

PMID- 19171095
TI  - [Proteomic screening of postsynaptic density proteins related with temporal lobe
      epilepsy].
AB  - OBJECTIVE: To explore the postsynaptic density (PSD) proteins related with the
      development of temporal lobe epilepsy (TLE). METHODS: Five SD rats were injected
      intra-peritoneally with lithium chloride and then pilocarpine twice to establish
      epilepsy models. At last 24 rats developed TLE, and 12 developed non-TLE. Then
      rats underwent intraperitoneal injection of normal saline (Norm group). Thirty
      days after the appearance of epilepticus the rats were decapitated with their
      brains taken out. The PSD proteins were extracted and purified by using sucrose
      gradient centrifugation and membrane sequence extraction, isolated by using two
      dimensional gel electrophoresis. PDQuest software was used to screen the
      specifically and differentially expressed protein spots. Partial differentially
      expressed PSD protein spots were selected and identified by MALDI-TOF-MS. Several
      identified proteins were detected in the PSD fraction by Western blotting.
      RESULTS: Compared with the non-TLE and Norm groups, there were 40 differential
      protein spots in the TLE group. The expression levels of heat shock protein-27
      (HSP-27), fructose-bisphosphate aldolase A (FBA), creatine kinase (CK), thyroid
      receptor-interacting protein 6 (TRIP6), myelin basic protein S (MBP), and LIM
      domain were up-regulated, but the expression levels of tubulin, actin, internexin
      alpha, peptidyl-prolyl cis-trans isomerase (PPIase), sorting nexin 3 (SNX3),
      aconitate hydratase (ACO), glyceradehydea-3-phosphate dehydrogenase (GADPH), and
      succinate-coenzyme A ligase (SCOAL) were down-regulated in the TLE group. The
      HSP27, tubulin-alpha, and SNX3 were in the PSD gels were immunostaining positive
      in the 3 groups. CONCLUSION: The differential expression of PSD proteins in TLE
      may be due to injury induced neural plasticity. But the degree thereof may
      contribute to the development of TLE. These identified proteins can be regarded
      as important candidates for or against the development of TLE.

PMID- 19171096
TI  - [Quantitative study of therapeutic efficacy on early intervention of hyperbaric
      oxygen to model of steroid-induced avascular osteonecrosis of femoral head by
      multi-slice perfusion imaging].
AB  - OBJECTIVE: To quantitatively evaluate the hemodynamic status in animal models of
      steroid-induced avascular osteonecrosis of femoral head (SANFH) by multislice CT
      (MSCT) perfusion imaging, and estimate the therapeutic efficacy on early
      intervention of hyperbaric oxygen (HBO) to improve the region blood flow (rBF) of
      ischemic femoral head. METHODS: Forty-eight New Zealand male rabbits were
      injected with Escherichia coli endotoxin and methyl-prednisolone to establish
      SANFH models and then divided into 3 subgroups to undergo MSCT to measure the
      rBF, regional blood volume (rBV), and mean transit time (MTT) to obtain perfusion
      maps at the femoral head epiphysis, metaphysic, and neck of femur, and then were
      killed to undergo histological examination of the bilateral femoral heads 2, 4,
      and 6 weeks later respectively (Groups M(2), M(4), and M(6)). Twenty-four rabbits
      underwent HOB treatment after the second injection of E. c. endotoxin for 1-3
      courses respectively (Groups H(1), H(2), and H(3)), and then underwent MSCT and
      pathological examination as described above. Eight rabbits were used as controls
      (Group N). RESULTS: (1) The rBF values of Groups M(2), M(4), and M(6) were all
      significantly lower than that of Group N (P < 0.001, < 0.001, and < 0.002). The
      rBF value of femoral head epiphysis of Group M(2) was remarkably lower than that
      of Group N, decreased to the lowest in Group M(4), and re-increased in Group
      M(6). The rBV value demonstrated similar change pattern in femoral head
      epiphysis. The MTT values of Groups M(2) and M(4) were longer than that of Group
      N, and then re-decreased in Group M(6). (2) It did differ significantly between
      the perfusion data of different femoral head anatomic regions in Groups M(2),
      M(4), M(6) and N (rBF: F = 52.190, P < 0.001; rBV: F = 42.677, P < 0.001; MTT: F
      = 3.09, P = 0.048). The changes of the perfusion data in femoral head epiphysis
      were more significant than those in other anatomic regions. (3) There were no
      statistically significant differences in the rBF value of the femoral head
      epiphysis and metaphysis (F = 2.081, P = 0.115; F = 1.142, P = 0.341), in the rBV
      value of the femoral metaphysis and neck of femur (F = 2.642, P = 0.059; F =
      1.568, P = 0.209), and the MTT value of all the anatomic regions (F = 1.111, P =
      0.347) among Groups H(1), H(2), H(3), and N. The rBF values of Groups H(1), H(2),
      and H(3) were statistically higher than those of the corresponding phase model
      groups (all P < 0.05). CONCLUSIONS: Able to detect hemodynamic status of femoral
      head, MSCT perfusion imaging technique may be used in the early detection of
      SANFH. Early intervention of HBO therapy can improve the blood perfusion of
      femoral head.

PMID- 19171097
TI  - [Prevention of allograft vasculopathy by transfection of calcitonin gene-related
      peptide].
AB  - OBJECTIVE: To explore suppression of allograft vasculopathy (AV) by transfer of
      the calcitonin gene-related peptide (CGRP). METHODS: The descending thoracic
      aortas from 39 Lewis rats were grafted to the abdominal aortas of 39 F344 rats,
      and then the recipient rats were randomized into 3 groups: Group A transfected
      with Ad5-CGRP-EGFP, a gene construct containing sequences from the adenoviral
      oncoprotein, CGRP, and enhanced green fluorescent protein, Group B, transfected
      with Ad5-EGFP containing sequences from the adenoviral oncoprotein and enhanced
      green fluorescent protein, and Group C without transfection. Four and 8 weeks
      later the abdominal aortas of 6 recipient rats from each were collected
      respectively. The degree of vascular obstruction was observed by microscopy.
      Frozen tissue sections were made and the inverted phase contrast fluorescence
      microscopy was used to observe the green fluorescence showing the expression of
      CGRP and enhanced green fluorescent protein (EGFP). RT-PCR was used to detect the
      expression of CGRP. Immunohistochemistry was used to examine the expression of
      inducible nitric oxide synthase (iNOS) and vascular cell adhesion molecule-1
      (VCAM-1). The apoptosis index (AI) was detected by TUNEL method. RESULTS: CGRP
      expression was positive in both Group A and B 4 weeks later and negative in both
      groups 8 weeks later. Group A is approximately normal in pathological morphology
      4 weeks later. The vascular luminal occlusion score of Group A was lower than
      Groups B and C 4 weeks later, and significantly higher than that I the same group
      (P < 0.05), however, still lower than those of Groups B and C 8 weeks later. The
      AI 4 weeks later of Group A was significantly lower than those of Groups B and
      group C, however, there was no significance in AI among the 3 groups. Four weeks
      later the VCAM-1 expression levels in the tunicae intima, media, and adventitia
      of Group A were all significantly lower than those of Group B C 4 weeks later,
      however, the iNOS expression level of Group A was only significantly lower than
      those of Groups B and C in the tunica intima 4 weeks later. CONCLUSION: The
      expression of CGRP effectively suppresses the development of AV 4 weeks after the
      operation.

PMID- 19171098
TI  - [Interaction between endogenous cystathionine synthase/hydrogen sulfide and heme
      oxygenase-1/carbon monoxide systems during myocardial ischemic-reperfusion:
      experiment with rats].
AB  - OBJECTIVE: To investigate the interaction between the cystathionine synthase gene
      (CBS)/hydrogen sulfide (H(2)S) and heme oxygenase-1 (HO-1)/carbon oxide (CO)
      systems during myocardial ischemia-reperfusion. METHODS: Twenty-four SD rats were
      randomly divided into 4 equal groups: ischemia-reperfusion (I/R) group undergoing
      intraperitoneal injection of normal saline (NS) and then 30 min later undergoing
      ligation of the left coronary artery (LCA) for 30 min, ischemia-reperfusion +
      zinc protoporphyrin (I/R + Z) group undergoing intraperitoneal injection of 45
      micromol/kg zinc protoporphyrin, a HO-1 inhibitor, 30 min before the ligation of
      LCA, ischemia-reperfusion + hydroxylamine (I/R + H) group, undergoing
      intraperitoneal injection of 5 mmol/L hydroxylamine, a CBS inhibitor, 30 min
      before the ligation of LCA, and ischemia-reperfusion + zinc protoporphyrin +
      hydroxylamine (I/R + Z + H) group undergoing intraperitoneal injection of zinc
      protoporphyrin and hydroxylamine 30 min before the ligation of LCA. Another 6
      rats underwent sham operation and intraperitoneal injection of NS 30 min before
      the operation and were used as control (C) group. The rats were killed 2 h after
      the reperfusion with their hearts taken out. Electron microscope was used to
      observe the mitochondrial structure. Homogenate of myocardium was prepared to
      examine the concentrations of H(2)S, CO, glutathione (GSH), malonyldialdehyde
      (MDA), activity of superoxide dismutase (SOD), and expression level of CBS-mRNA
      and HO-1-mRNA. RESULT: The concentration of CO, H(2)S, GSH, and MDA increased,
      SOD activity decreased, and HO-1-mRNA and CBS-mRNA expression levels increased in
      Group I/R as compared with Group C (all P < 0.01). In Group I/R + Z the CO level
      decreased, H(2)S and GSH levels increased, and HO-1-mRNA expression level
      decreased, but CBS-mRNA expression level increased as compared with Group I/R
      (all P < 0.05). In Group I/R + H the H(2)S and GSH levels decreased, CO level
      increased, and HO-1-mRNA expression level increased and CBS-mRNA expression level
      decreased as compared with Group I/R (all P < 0.05). In Group I/R + Z + H the
      H(2)S, CO, GSH, and SOD levels decreased, MDA level increased, and HO-1-mRNA and
      CBS-mRNA expression levels decreased as compared with Group I/R (all P < 0.05).
      Electron microscopy found that mitochondrial structure was destroyed in the
      Groups I/R, I/R + Z, I/R + H, and most seriously in Group I/R + Z + H.
      CONCLUSION: Both CBS/H(2)S and HO-1/CO systems play a protective role in
      myocardial ischemia-reperfusion and they interact on each other.

PMID- 19171099
TI  - [Navigated percutaneous placement of iliosacral screws using intra-operative
      three-dimensional imaging].
AB  - OBJECTIVE: To investigate the effect of a new technique of navigated percutaneous
      placement of iliosacral screws using intra-operative three-dimensional (3D)
      imaging. METHODS: Sixteen patients with hip fracture were placed in supine
      position. After the reference marker was fixed on the iliac crest, a 3-D C-arm
      navigation system was used intra-operatively to obtain 3D images that were
      transferred to the navigation system by an automatic. Registration process to
      calculate the length of screw and direction to insert it. A navigated pointer
      defined the entry point, while navigated percutaneous drilling was done
      accordingly with a navigated drill bit in combination with a navigated drill
      sleeve under permanent dynamic control on the navigation screen without further
      intra-operative fluoroscopic imaging. A control intra-operative 3D scan was used
      to observe the position of the screws, while for didactic reasons another
      postoperative CT scan was done. RESULTS: Twenty screws were successfully inserted
      into the first sacral vertebral bodies of the 16 patients. No additional intra
      operative and postoperative complications occurred. The average operation time
      was 80 minutes and the average intra-operative radiation time was 1.13 minutes.
      Four patients underwent bilateral iliosacral fixation with longer operation time
      (152 minutes) and radiation time (1.56 minutes). The post-operative 3D scanning
      showed good results. No screws penetrated into the sacral canal or foramen. The
      reduction of fracture or dislocation and the position of iliosacral screws were
      all judged satisfactory. CONCLUSION: Compared with the conventional fluoroscopy
      method, navigated percutaneous placement of iliosacral screws under intra
      operative 3D imaging reduces the radiation time and improves the accuracy. It is
      feasible and useful though there are some disadvantages such as the inferior
      image quality compared to CT scan, prolonged operation time and higher overall
      cost.

PMID- 19171105
TI  - Outcome of aspirin treatment of antiphospholipid antibody-positive patients.

PMID- 19171106
TI  - The use of opioids in the treatment of osteoarthritis: when, why, and how?
AB  - As life expectancy increases every decade, the incidence and prevalence of
      osteoarthritis (OA) also will increase. Despite progress in our knowledge of the
      pathophysiology of OA, the management of OA-mediated pain continues to challenge
      physicians. Concern regarding the cardiovascular effects of cyclooxygenase-2
      inhibitors and the gastrointestinal and renal side effects of nonsteroidal anti
      inflammatory drugs (NSAIDs) in general has limited the use of these medications
      in the management of chronic non-cancer pain. Appropriately dosed and monitored
      use of opioids for OA pain, when more conservative methods have failed, has
      potentially fewer life-threatening complications associated with it than the more
      commonly and often less successfully employed pharmacotherapeutic approaches to
      care. When used as part of a multimodal approach to pain control, opioids are a
      safe and effective treatment for joint pain, including that of OA. Patients for
      whom NSAIDs are contraindicated, or for whom combined acetaminophen, tramadol,
      and NSAID therapy is ineffective, may be started on low-dose opioids and titrated
      as needed and tolerated. Patient education and informed consent, exercise,
      complementary medicine, and the use of a controlled substance agreement increases
      the likelihood of patient compliance with treatment guidelines, improving
      functional capacity and quality of life.

PMID- 19171107
TI  - The biomechanics of osteoarthritis: implications for therapy.
AB  - The pathophysiology of osteoarthritis (OA) has been extensively studied. However,
      the basic approach to therapy, which consists of pain relief and maintenance of
      function, has not changed for decades. At present, there are no nonsurgical
      methods that clearly interfere with the natural history of OA or provide
      prolonged pain palliation. Much of OA disease progression is mediated by aberrant
      biomechanical forces or through pathologic responses to those forces. As
      understanding of these mechanisms improves, novel therapeutic approaches are
      being studied that may provide prolonged reductions in loading of OA joints.
      These new therapies may ultimately be shown to retard disease progression and
      palliate pain. This article reviews some of these strategies.

PMID- 19171108
TI  - WNT Signaling in osteoarthritis and osteoporosis: what is the biological
      significance for the clinician?
AB  - Osteoporosis and osteoarthritis are common musculoskeletal disorders in which
      cause and outcome are determined by genetic and environmental factors. The WNT
      signaling pathway plays an important role in skeletal development and growth.
      Polymorphisms in a number of genes that belong to this pathway are associated
      with osteoarthritis and/or osteoporosis. This suggests a role for this molecular
      signaling pathway in postnatal joint and bone homeostasis and pathology.
      Increased activity of WNT signaling strengthens the bone but may have adverse
      effects on the articular cartilage. Frizzled related protein (FRZB) plays a role
      in both bone and cartilage. Better understanding of the WNT pathway and its
      modulators may lead to specific therapeutics for both osteoarthritis and
      osteoporosis. This review focuses on recent studies in human genetics and animal
      models and highlights the potential clinical relevance of this rapidly evolving
      field of research.

PMID- 19171109
TI  - Cardiovascular risk associated with nonsteroidal anti-inflammatory drugs.
AB  - Since the introduction of selective cyclooxygenase-2 inhibitors (coxibs), there
      has been an ongoing discussion about the cardiovascular (CV) safety of coxibs and
      the traditional nonsteroidal anti-inflammatory drugs (NSAIDs). Available data
      about the CV safety of NSAIDs come mostly from meta-analyses and a few clinical
      trials. Current evidence suggests that NSAIDs may increase the risk of CV events.
      Naproxen might be associated with lower risk, but available data are not
      conclusive. Recent recommendations on the treatment of patients with NSAIDs favor
      the use of naproxen in patients with increased CV risk. Therefore, this review
      focuses on data about naproxen and examines CV risk with ibuprofen and non
      naproxen NSAIDs. In addition, data about CV safety of paracetamol (acetaminophen)
      are presented.

PMID- 19171110
TI  - Aspirin and acetaminophen: should they be available over the counter?
AB  - Traditional nonsteroidal anti-inflammatory drugs block cyclooxygenase (COX). They
      are the most widely used drugs for pain relief. They are indispensable for their
      effects but are condemned for their adverse drug reactions. Two COX inhibitors,
      acetaminophen and aspirin, are the most widely used over-the-counter drugs. They
      have low (but useful) therapeutic activity, but they are endowed with specific
      risks that are not seen with most other COX inhibitors. Both are lethal if taken
      in overdose. Each is stigmatized by severe adverse effects. Aspirin results in
      prolonged inhibition of blood coagulation, and acetaminophen can result in liver
      toxicity at normal dose and liver failure at higher dose. Both drugs cause many
      deaths every year. We recommend that the status of both drugs be changed to
      prescription only. Their continued availability over the counter poses an
      unacceptable risk to the general population.

PMID- 19171111
TI  - Antiphospholipid antibodies in rheumatoid arthritis: identifying the dominoes.
AB  - Antiphospholipid antibodies (aPL) occur in a variety of autoimmune, malignant,
      and infectious diseases, with or without the thrombotic or obstetric sequelae
      that characterize the antiphospholipid syndrome. Although many studies have
      focused on the clinical implications of aPL in systemic lupus erythematosus, few
      have specifically addressed the questions facing rheumatologists caring for
      rheumatoid arthritis patients who are concomitantly positive for aPL. Such a
      clinical scenario requires current knowledge of antiphospholipid syndrome
      diagnosis criteria, test reliability, conditions causing temporal positivity of
      aPL, and treatment risks and benefits. Recently researched factors possibly
      integral to rheumatoid arthritis's increased morbidity and mortality and related
      to aPL include oxidatively modified low-density lipoprotein antibodies,
      homocysteine, annexins, infectious agents, beta estradiol, and specific gene
      polymorphisms. This review presents current scientific research addressing the
      pathophysiologic mechanisms and clinical implications of aPL in rheumatoid
      arthritis.

PMID- 19171112
TI  - Renal manifestations of the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome is characterized by recurrent arterial and venous
      thromboses and pregnancy morbidity in association with antiphospholipid
      antibodies. Recurrent thrombotic events are associated with significant morbidity
      and mortality. Renal involvement encompasses the whole renal vasculature and may
      lead to proteinuria, renal impairment, hypertension, and end-stage renal failure.
      Renal involvement is especially difficult to distinguish from glomerulonephritis
      when the antiphospholipid syndrome develops in patients with systemic lupus
      erythematosus. This article reviews the diagnosis and treatment of the major
      features of this syndrome, with particular reference to the kidney.

PMID- 19171113
TI  - Atherosclerosis in autoimmune diseases.
AB  - Lipid peroxidation occurs frequently in patients with systemic autoimmune
      diseases and contributes to autoimmune vascular inflammation. Oxidized low
      density lipoprotein (oxLDL) interacts with beta2-glycoprotein I (beta2GPI),
      forming oxLDL/beta2GPI complexes. Circulating oxLDL/beta2GPI complexes and
      autoantibodies to these complexes have been demonstrated in patients with
      systemic lupus erythematosus and antiphospholipid syndrome. These findings
      suggest an immunogenic nature of the complexes and an active proatherogenic role
      in autoimmunity. Biochemical characterization of the complexes and
      immunohistochemical studies of atherosclerotic lesions suggest that most of the
      complexes originate in the arterial wall and are released into circulation. The
      in vitro macrophage uptake of oxLDL/beta2GPI complexes increased significantly in
      the presence of antiphospholipid antibodies (anti-beta2GPI), suggesting that
      macrophage Fcgamma receptors are involved in the lipid intracellular influx that
      leads to foam cell formation. These findings provide an immunologic explanation
      for the accelerated development of atherosclerosis seen in systemic lupus
      erythematosus and antiphospholipid syndrome.

PMID- 19171114
TI  - Neonatal effects of maternal antiphospholipid syndrome.
AB  - Antiphospholipid antibodies (aPL) can impair the physiologic development of a
      fetus during pregnancy not only by causing thrombosis of the placental vessels,
      but also by directly binding throphoblast cells and modifying their functions.
      Consequently, the presence of aPL in pregnant women is linked to an increased
      rate of pregnancy complications. These include recurrent early miscarriages, late
      fetal losses, and hypertensive disorders of gestation. In this clinical setting,
      preeclampsia is usually early and severe and can be complicated by the syndrome
      of hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome).
      The close association between aPL and obstetric pathology supports the inclusion
      of these manifestations in the clinical classification criteria of
      antiphospholipid syndrome. About 30% of children born to mothers with aPL
      passively acquire these autoantibodies; fortunately, the occurrence of thrombosis
      seems extremely rare in these babies. The prospective ongoing studies of children
      born to antiphospholipid syndrome patients reassure us about their general good
      health; however, some data suggest that learning difficulties might occur,
      possibly related to in utero exposure to aPL.

PMID- 19171115
TI  - Mechanisms of antiphospholipid-induced thrombosis: effects on the protein C
      system.
AB  - An acquired resistance to activated protein C (APC) has been demonstrated in
      patients with antiphospholipid antibodies (aPL). Recent studies report
      interactions between beta2 glycoprotein I (beta2GPI) and prothrombin-binding
      antibodies and the protein C system. Some aPL in patients recognize one or more
      conformational epitopes shared by beta2GPI and catalytic domains of APC. Both
      beta2GPI and anti-prothrombin antibodies are associated with APC resistance.
      Several clinical studies have focused on an association between aPL and APC
      resistance, determined by classic activated partial thromboplastin time-based
      tests. It has been shown in most studies that APC resistance was associated with
      lupus anticoagulants. APC resistance is also associated with thrombosis,
      especially venous thromboembolism. Several recent studies have reported a novel
      integrated approach of coagulation using calibrated automated thrombography. This
      technique allows an approach of APC sensitivity without interference with lupus
      anticoagulants. Clinical associations between APC resistance and thromboembolic
      events have been demonstrated.

PMID- 19171117
TI  - Electron transport chains and bioenergetics of respiratory nitrogen metabolism in
      Wolinella succinogenes and other Epsilonproteobacteria.
AB  - Recent phylogenetic analyses have established that the Epsilonproteobacteria form
      a globally ubiquitous group of ecologically significant organisms that comprises
      a diverse range of free-living bacteria as well as host-associated organisms like
      Wolinella succinogenes and pathogenic Campylobacter and Helicobacter species.
      Many Epsilonproteobacteria reduce nitrate and nitrite and perform either
      respiratory nitrate ammonification or denitrification. The inventory of
      epsilonproteobacterial genomes from 21 different species was analysed with
      respect to key enzymes involved in respiratory nitrogen metabolism. Most
      ammonifying Epsilonproteobacteria employ two enzymic electron transport systems
      named Nap (periplasmic nitrate reductase) and Nrf (periplasmic cytochrome c
      nitrite reductase). The current knowledge on the architecture and function of the
      corresponding proton motive force-generating respiratory chains using low
      potential electron donors are reviewed in this article and the role of membrane
      bound quinone/quinol-reactive proteins (NapH and NrfH) that are representative of
      widespread bacterial electron transport modules is highlighted. Notably, all
      Epsilonproteobacteria lack a napC gene in their nap gene clusters. Possible roles
      of the Nap and Nrf systems in anabolism and nitrosative stress defence are also
      discussed. Free-living denitrifying Epsilonproteobacteria lack the Nrf system but
      encode cytochrome cd(1) nitrite reductase, at least one nitric oxide reductase
      and a characteristic cytochrome c nitrous oxide reductase system (cNosZ).
      Interestingly, cNosZ is also found in some ammonifying Epsilonproteobacteria and
      enables nitrous oxide respiration in W. succinogenes.

PMID- 19171116
TI  - Protective effect of the AT137RQ and ARQK176 PrP allele against classical scrapie
      in Sarda breed sheep.
AB  - The susceptibility of sheep to scrapie is under the control of the host's prion
      protein (PrP gene and is also influenced by the strain of the agent. PrP
      polymorphisms at codons 136 (A/V), 15 (R/H) and 171 (Q/R/H) are the main
      determinants of susceptibility/resistance of sheep to classical scrapie. They are
      combined in four main variants of the wild-type ARQ allele: VRQ, AHQ, ARH and
      ARR. Breeding programmes have been undertaken on this basis in the European Union
      and th USA to increase the frequency of the resistant ARR allele in sheep
      populations. Herein, we report th results of a multi-flock study showing the
      protective effect of polymorphisms other than those a codons 136, 154 and 171 in
      Sarda breed sheep. All ARQ/ARQ affected sheep (n = 154) and 37 negative ARQ/ARQ
      controls from four scrapie outbreaks were submitted to sequencing of the Pr gene.
      The distribution of variations other than those at the standard three codons,
      between scrapie cases and negative controls, was statistically different in all
      flocks. In particular, the AT(137)RQ an ARQK(176) alleles showed a clear
      protective effect. This is the first study demonstrating a protective influence
      of alleles other than ARR under field conditions. If further investigations in
      other sheep breeds and with other scrapie sources confirm these findings, the
      availability of various protective alleles in breeding programmes of sheep for
      scrapie resistance could be useful in breeds with a low frequency of the ARR
      allele and would allow maintaining a wider variability of the PrP gene.

PMID- 19171118
TI  - Proline 146 is critical to the structure, function and targeting of sod2, the
      Na+/H+ exchanger of Schizosaccharomyces pombe.
AB  - Sod2 is the Na(+)/H(+) exchanger of the fission yeast Schizosaccharomyces pombe
      that is principally responsible for salt tolerance. We examined the role of nine
      polar, membrane associated amino acids in the ability of the protein to confer
      salt tolerance in S. pombe. Wild type sod2 protein with a C-terminal GFP tag
      effectively rescued salt tolerance in S. pombe with deleted endogenous sod2. Sod2
      protein with the mutations P163A, P183A, D298N, D389N, E390Q, E392Q and E397Q
      also conveyed salt tolerance as effectively as the wild type sod2 protein. In
      contrast, the mutation P146A resulted in a protein that did not convey salt
      tolerance nearly as effectively as the wild type and did not extrude Na(+) as
      well as the wild type. Mutation of Pro(146) to Ser, Asp or Lys had an
      intermediate effect. Mutation of Thr(142) to Ser resulted in a slightly defective
      protein. Western blot analysis showed that all mutant proteins were expressed at
      similar levels as wild type sod2 protein. Examination of the localization of the
      proteins showed that wild type and most sod2 mutants were present in the plasma
      membrane while the P146A mutant had an intracellular localization. Limited
      tryptic digestion suggested that the P146A sod2 protein had a change in
      conformation in comparison to the wild type protein. The results suggest that
      Pro(146) is an amino acid critical to sod2 structure, function and localization.

PMID- 19171119
TI  - The ligand environment of zinc stored in vesicles.
AB  - Zinc serves regulatory functions in cells and thus, several mechanisms exist for
      tight control of its homeostasis. One mechanism is storage in and retrieval from
      vesicles, so-called zincosomes, but the chemical speciation of zincosomal zinc
      has remained enigmatic. Here, we determine the intravesicular zinc-coordination
      in isolated zincosomes in comparison to intact RAW264.7 murine macrophage cells.
      In elemental maps of a cell monolayer, generated by microbeam X-ray fluorescence,
      zincosomes were identified as spots of high zinc accumulation. A fingerprint for
      the binding motif obtained by muXANES (X-ray absorption near edge structure)
      matches the XANES from isolated vesicles; zinc is not free, but present as a
      complexed form (average coordination; 1.0 sulfur, 2,5 histidines 30 and 1.0
      oxygen), resembling regulatory or catalytic zinc sites in proteins. Such
      coordination enables reversible binding, acting as a 'zinc sink', facilitating
      the accumulation of high amounts of zinc against a concentration gradient.

PMID- 19171120
TI  - Prediction of protein-protein interactions based on PseAA composition and hybrid
      feature selection.
AB  - Based on pseudo amino acid (PseAA) composition and a novel hybrid feature
      selection frame, this paper presents a computational system to predict the PPIs
      (protein-protein interactions) using 8796 protein pairs. These pairs are coded by
      PseAA composition, resulting in 114 features. A hybrid feature selection system,
      mRMR-KNNs-wrapper, is applied to obtain an optimized feature set by excluding
      poor-performed and/or redundant features, resulting in 103 remaining features.
      Using the optimized 103-feature subset, a prediction model is trained and tested
      in the k-nearest neighbors (KNNs) learning system. This prediction model achieves
      an overall accurate prediction rate of 76.18%, evaluated by 10-fold cross
      validation test, which is 1.46% higher than using the initial 114 features and is
      6.51% higher than the 20 features, coded by amino acid compositions. The PPIs
      predictor, developed for this research, is available for public use at
      http://chemdata.shu.edu.cn/ppi.

PMID- 19171121
TI  - The multidrug resistance efflux complex, EmrAB from Escherichia coli forms a
      dimer in vitro.
AB  - Tripartite efflux systems are responsible for the export of toxins across both
      the inner and outer membranes of gram negative bacteria. Previous work has
      indicated that EmrAB-TolC from Escherichia coli is such a tripartite system,
      comprised of EmrB an MFS transporter, EmrA, a membrane fusion protein and TolC,
      an outer membrane channel. The whole complex is predicted to form a continuous
      channel allowing direct export from the cytoplasm to the exterior of the cell.
      Little is known, however, about the interactions between the individual
      components of this system. Reconstitution of EmrA+EmrB resulted in co-elution of
      the two proteins from a gel filtration column indicating formation of the EmrAB
      complex. Electron microscopic single particle analysis of the reconstituted EmrAB
      complex revealed the presence of particles approximately 240x140A, likely to
      correspond to two EmrAB dimers in a back-to-back arrangement, suggesting the
      dimeric EmrAB form is the physiological state contrasting with the trimeric
      arrangement of the AcrAB-TolC system.

PMID- 19171122
TI  - Targeted deletion of hepatocyte Ikkbeta confers growth advantages.
AB  - Mice lacking hepatocyte IKKbeta (Ikkbeta(Delta hep)) are defective in TNFalpha
      activation of hepatocellular transcription factor NF-kappaB, and highly
      susceptible to hepatotoxicity. Following diethylnitrosamine (DEN) exposure,
      Ikkbeta(Delta hep) mice develop more hepatocellular carcinoma (HCC) than control
      mice due partly to enhanced DEN-induced hepatocyte death. Here we show that
      Ikkbeta(Delta hep) hepatocytes display growth advantages over normal hepatocytes
      consisting of precocious PCNA and cyclin D1 expression during liver regeneration
      (shortened hepatocyte G(0)-->G(1) transitions), and enhanced recovery efficiency,
      cyclin D1 expression and cell proliferation after plating. Ex vivo deletion of
      Ikkbeta also accelerates hepatocyte growth. Ikkbeta(Delta hep) hepatocyte
      proliferative responses show heightened sensitivity to TGFalpha and TNFalpha, and
      heightened expression of fibronectin, collagens I/III, nidogen, beta-actin and
      integrin beta1 mRNAs. These findings suggest that altered mitogen signaling and
      expression of extracellular matrix and its associated components underlie growth
      advantages. Increased HCC development in Ikkbeta(Delta hep) mice may also be
      caused by growth advantages of surviving Ikkbeta-deleted hepatocytes.

PMID- 19171123
TI  - Hepatocyte growth factor prevents multiple organ injuries in endotoxemic mice
      through a heme oxygenase-1-dependent mechanism.
AB  - Acute renal failure (ARF) and acute respiratory distress syndrome (ARDS) are
      still lethal diseases during sepsis, whereas heme oxygenase-1 (HO-1) elicits a
      host defense response to sepsis. Herein, we provide evidence that hepatocyte
      growth factor (HGF) prevents ARF and ARDS via enhanced induction of HO-1.
      Lipopolysaccharide (LPS)-treated mice manifested renal and pulmonary injuries
      similar to those observed in septic patients, while HGF enhanced the HO-1
      induction in renal tubular cells and in lung macrophages. As a result, onsets of
      ARF and ARDS were blocked by HGF in septic mice. Notably, an HO-1 inhibitor
      (SnPP) diminished the protective effects of HGF on LPS-induced organ injuries.
      Furthermore, the inhibitory effect of HGF on up-regulation of interleukin-1beta
      and interleukin-18 was largely restored by SnPP. This is the first report showing
      that "growth factor therapy" successfully inhibits both ARDS and ARF during
      endotoxemia, partially via HO-1-dependent suppression of hyper-cytokinemia.

PMID- 19171124
TI  - Postnatal ontogenesis of molecular clock in mouse striatum.
AB  - Striatum is an important brain area whose function is related to motor, emotion
      and motivation. Interestingly, biological and physiological circadian rhythms
      have been found in the striatum extensively, suggesting molecular clock machinery
      works efficiently therein. However, the striatal expression profiles of clock
      genes have not been characterized systematically. In addition, little is known
      about when the expression rhythms start during postnatal ontogenesis. In the
      present study, 24 h mRNA oscillations of 6 principle clock genes (Bmal1, Clock,
      Npas2, Cry1, Per1 and Rev-erb alpha) were examined in mouse striatum, at early
      postnatal stage (postnatal day 3), pre-weaning stage (postnatal day 14) and in
      adult (postnatal day 60). At P3, no daily oscillation was found for all clock
      genes. At P14, a significant time effect was identified only for Rev-erb alpha
      and Npas2. At P60, the daily oscillations of these clock genes were at least
      borderline significant, with peak time at Circadian time (CT) 01 for Bmal1,
      Clock, Npas2 and Cry1; at CT 13 for Per1; and at CT 07 for Rev-erb alpha. In
      addition, the overall mean mRNA levels of these clock genes also underwent a
      dynamic change postnatally. For Bmal1, Clock, Npas2, Per1 and Rev-erb alpha, the
      expression level increased throughout the postnatal ontogenesis from P3, P14 to
      P60. For Cry1, however, the abundance at P3 and P60 were similar while that at
      P14 was much lower. In conclusion, the striatal molecular clock machinery,
      although works efficiently in adult, develops gradually after birth in mice.

PMID- 19171125
TI  - Early postnatal enriched environment decreases retinal degeneration induced by
      monosodium glutamate treatment in rats.
AB  - Environmental enrichment is known to influence the development of the nervous
      system and it provides beneficial effects in various kinds of brain lesions.
      Enriched housing conditions also influence the development and functioning of the
      visual system. The aim of the present study was to investigate whether retinal
      degeneration induced by neonatal monosodium glutamate (MSG) in rats can be
      ameliorated by expanded cage size or enriched environment. Control rats were kept
      in a regular cage, another group of pups was kept in an expanded cage and a third
      group was kept under complex environmental enriched conditions from the first
      postnatal day. Half of the rats received MSG treatment on postnatal days 1, 5,
      and 9, while the other half of the groups received only saline treatment. Retinas
      were removed at 5 weeks of age and processed for histological analysis.
      Microscopical analysis revealed a substantial inner retinal degeneration in MSG
      treated animals: the retinal thickness was less than 25% of the normal retinas,
      and the inner layers were completely fused. Expanded cage environment had a
      significant protective effect: the layers of the retina were well visible, and
      the thickness of the entire retina had a nearly 50% amelioration. Best results
      were obtained in retinas from rats living in enriched environment: the retina
      suffered only an approximately 25% reduction in thickness, and all layers were
      significantly thicker than in MSG-treated retinas. In summary, the present study
      showed that expanded field provided some degree of neuroprotection, while a
      complex environmental enrichment led to a manifest protection against retinal
      degeneration induced by neonatal MSG treatment in rats.

PMID- 19171126
TI  - Predicting synchronous and asynchronous network groupings of hippocampal
      interneurons coupled with dendritic gap junctions.
AB  - Direct electrical communication between central nervous system (CNS) neurons
      including those in the hippocampus is well-established. This form of
      communication is mediated by gap junctions and it is known that this coupling is
      important for brain rhythms such as gamma (20-80 Hz) which occur during active
      behavioural states. It is also known that gap junctions are present at several
      locations along the dendrites of hippocampal interneurons including parvalbumin
      positive basket cell types. Weakly coupled oscillator theory, which uses phase
      response curves (PRCs), has been used to understand and predict the dynamics of
      electrically coupled networks. Here we use compartmental models of hippocampal
      basket cells with different levels of basal and apical spike attenuation together
      with the theory to show that network output can be broken down into three
      groupings: synchronous, asynchronous and antiphase-like patterns. Moreover,
      quantified PRCs can be used as a rule of thumb to determine the occurrence of a
      particular grouping under weak coupling conditions, which in turn implies that
      spike delays are critical factors in determining network output. In moving beyond
      weak coupling to encompass the full physiological regime of coupling strengths
      with network simulations, we note that it is important to be able to
      differentiate between these different groupings as it affects how the network
      responds with modulation. Specifically, an asynchronous grouping provides more
      dynamic richness as a larger range of phase-locked states can be expressed with
      strength changes. From a functional viewpoint it may be that modulation of
      electrically coupled networks are key to controlling cell assemblies that
      contribute to information coding brain substrates.

PMID- 19171127
TI  - Introduction of a continual RIII reflex threshold tracking algorithm.
AB  - INTRODUCTION: The RIII reflex is used in fundamental and clinical pain research.
      Here we introduce a continual reflex threshold tracking algorithm to facilitate
      investigations of the time courses of influences on the threshold. METHODS: First
      we investigated the probability of reflex occurrence at the threshold estimated
      by the continual algorithm and the changes of the threshold over the time during
      continual recordings of 100 min duration in 10 subjects. Secondly we compared the
      threshold estimates of the continual algorithm with those of a standard algorithm
      of threshold estimation in 52 subjects and compared the differences between the
      two methods with the test-retest-variability of each method. RESULTS: The average
      probability of reflex occurrence at the threshold estimated by the continual
      algorithm was 48.7% (SD = 3.2%). Changes of the RIII reflex threshold over the
      time were not significant (Friedman test, p>0.05). The variability between the
      thresholds determined by the different algorithms (test: SD = 2.50 mA, retest: SD
      = 1.80 mA) was lower than the variability between test and retest (standard
      algorithm: SD = 4.32 mA, continual algorithm: SD = 4.44 mA). DISCUSSION: The
      continual algorithm can be used for a continuous estimation of the reflex
      threshold at the 50% probability of reflex-occurrence. No evidence of habituation
      was detected. This allows for investigations of the time courses of
      pharmacological and physiological influences on the reflex threshold by using
      this algorithm. The lower variability between the continual algorithm and the
      standard algorithm compared to the variability between tests and retests of the
      methods allows for interchangeable conclusions drawn from data obtained with both
      methods.

PMID- 19171128
TI  - Diagnosis and spectrum of melamine-related renal disease: plausible mechanism of
      stone formation in humans.
AB  - BACKGROUND: An epidemic of urinary stones affecting children after consumption of
      melamine tainted milk is unfolding. We defined clinicopathological features of
      the disease for diagnosis, monitoring, and treatment of this group of patients.
      METHODS: A clinicopathological study on exposed children with ultrasonographic
      evidence of urolithiasis was conducted. Melamine and cyanuric acid levels in the
      urine were determined by mass spectrometry. RESULTS: Disease severity varied from
      acute renal failure with hydronephrosis to symptomatic or asymptomatic stones
      with or without abnormal urinalysis. All cases were aged <3 y with >50% cases
      having predisposing urinary metabolic risk factors for urolithiasis. Most of the
      stones were located in the renal pelvis and measured 2.5-18 mm by
      ultrasonography. We found a strong correlation between renal stone size and
      urinary melamine concentration. For stones <10 mm, a 10 microg/mmol creatinine
      increase in urinary melamine concentration is associated with approximately 1 mm
      increase in the size of the stone. The high degree of correlation strongly
      suggests that melamine is related to stone formation in humans. Using ROC
      analysis, we propose that patients who have a persistent melamine level above the
      optimal cut-off value of 7.1 microg melamine/mmol creatinine in urine might have
      a significant exposure of melamine-tainted products. Unlike melamine, urinary
      cyanuric acid is not significantly different between cases and controls.
      Pathophysiological findings from feeding animals with melamine and cyanuric acid
      may not be directly applicable to humans. CONCLUSION: Both melamine and urine
      metabolic lithogenic factors are important for the formation of melamine-related
      stones. Apart from aiding with case screening and confirmation, the urine
      melamine level might as well be an indicator of residual melamine load in the
      body and thus is useful for following-up and monitoring of the confirmed cases.
      As the stones are small and can be passed out spontaneously, follow-up of these
      patients with urine melamine will be a convenient tool for monitoring the
      melamine load of the patients.

PMID- 19171129
TI  - Interaction of notochord-derived fibrinogen-like protein with Notch regulates the
      patterning of the central nervous system of Ciona intestinalis embryos.
AB  - The midline organ the notochord and its overlying dorsal neural tube are the most
      prominent features of the chordate body plan. Although the molecular mechanisms
      involved in the formation of the central nervous system (CNS) have been studied
      extensively in vertebrate embryos, none of the genes that are expressed
      exclusively in notochord cells has been shown to function in this process. Here,
      we report a gene in the urochordate Ciona intestinalis encoding a fibrinogen-like
      protein that plays a pivotal role in the notochord-dependent positioning of
      neuronal cells. While this gene (Ci-fibrn) is expressed exclusively in notochord
      cells, its protein product is not confined to these cells but is distributed
      underneath the CNS as fibril-like protrusions. We demonstrated that Ci-fibrn
      interacts physically and functionally with Ci-Notch that is expressed in the
      central nervous system, and that the correct distribution of Ci-fibrn protein is
      dependent on Notch signaling. Disturbance of the Ci-fibrn distribution caused an
      abnormal positioning of neuronal cells and an abnormal track of axon extension.
      Therefore, it is highly likely that the interaction between the notochord-based
      fibrinogen-like protein and the neural tube-based Notch signaling plays an
      essential role in the proper patterning of CNS.

PMID- 19171130
TI  - Mizoribine may suppress bone erosion in patients with rheumatoid arthritis by
      inhibiting osteoclastogenesis.
AB  - Mizoribine is a disease-modifying anti-rheumatic drug (DMARD) that is used in the
      treatment of rheumatoid arthritis. However, clinical use of the drug is
      restricted to a few Asian countries due to a lack of comprehensive evidence on
      its effectiveness. The inhibitory effect of the drug on human osteoclastogenesis
      was investigated in the hopes of providing some clear evidence. Mizoribine was
      found to inhibit in vitro osteoclastogenesis in a dose-dependent manner. In
      addition, the size of the pit area was closely related to the number of
      osteoclasts in a bone resorption assay. However, mizoribine did not affect the
      phosphorylation of MAP kinase (p38, JNK, ERK), the degradation of IkappaBalpha,
      or receptor activator of NF-kappaB ligand (RANKL) expression in fibroblast-like
      synoviocytes stimulated with IL-1beta. These results suggested that mizoribine
      may partially suppress osteoclastogenesis, leading to progressive bone erosion by
      inhibiting the growth or the signaling pathway of precursor cells to form
      osteoclasts rather than fibroblast-like synoviocytes.

PMID- 19171131
TI  - Effects of the combination of dipeptidyl peptidase-IV inhibitor ASP8497 and
      antidiabetic drugs in streptozotocin-nicotinamide-induced mildly diabetic mice.
AB  - Several combination therapies have been investigated in an effort to achieve and
      maintain glycemic control in patients with type 2 diabetes. In this study, we
      combined the novel dipeptidyl peptidase (DPP)-IV inhibitor ASP8497 with the
      antidiabetic drugs metformin, glibenclamide, voglibose, rosiglitazone, and
      insulin to examine the effects of each combination on glucose tolerance in
      streptozotocin-nicotinamide-induced mildly diabetic mice. Single treatments with
      ASP8497 (1 mg/kg), metformin (300 mg/kg), glibenclamide (3 mg/kg), voglibose (0.3
      mg/kg), rosiglitazone (10 mg/kg), or insulin (0.2 IU/kg) significantly improved
      glucose tolerance during the liquid meal tolerance test. In addition, combination
      treatment with ASP8497 and each antidiabetic drug additively improved glucose
      tolerance. Among these, the combination of ASP8497 and glibenclamide or insulin
      additively ameliorated glucose tolerance with an additive increase in the plasma
      insulin level; however, it did not affect the fasting blood glucose lowering
      effects of glibenclamide or insulin. These profiles indicate that the combination
      of ASP8497 with existing antidiabetic drugs could be useful for correcting the
      postprandial hyperglycemia seen with type 2 diabetes.

PMID- 19171132
TI  - Telmisartan, an angiotensin II type 1 receptor blocker, prevents the development
      of diabetes in male Spontaneously Diabetic Torii rats.
AB  - To assess the beneficial effects of the angiotensin II type 1 receptor blocker
      telmisartan on a non-obese animal model of reduced function and mass of islet
      beta-cells prior to the development of diabetes, Spontaneously Diabetic Torii
      (SDT) rats were treated with telmisartan at 8 weeks of age. At 24 weeks of age,
      the treatment with telmisartan dose-dependently ameliorated hyperglycemia and
      hypoinsulinemia, and high-dose (5 mg/kg/day) treated SDT rats did not developed
      diabetes. Real-time RT-PCR analysis revealed that treatment with high-dose
      telmisartan reduced mRNA expression of local renin-angiotensin system (RAS)
      components, components of NAD(P)H oxidase, transforming growth factor-beta1 and
      vascular endothelial growth factor in the pancreas of male SDT rats.
      Immunohistochemical and Western blot analyses revealed that treatment with
      telmisartan also reduced expression of p47(phox). These results suggest that
      treatment with telmisartan reduces oxidative stress by local RAS activation and
      protects against islet beta-cell damage and dysfunction. These findings provide
      at least a partial explanation for the reduced incidence of new-onset diabetes
      that has been observed in several clinical trials involving angiotensin II type 1
      receptor blockers and ACE inhibitors.

PMID- 19171133
TI  - Molecular mechanism of KCl-induced relaxation of the esophagus.
AB  - KCl (40 mM) caused reproducible relaxations in frog esophagus. N(G)-nitro-L
      arginine (L-NOARG; 1-100 microM), a steriospecific inhibitor of nitric oxide
      synthase (NOS), completely inhibited the relaxations induced by KCl but not those
      induced by vasoactive intestinal polypeptide (VIP) antagonist. The inhibitory
      effect of L-NOARG was prevented by L-arginine (L-ARG; 0.1-1 mM), the precursor of
      nitric oxide (NO) biosynthesis, but not by D-arginine (D-ARG; 0.1-0.5 mM), the
      enantiomer of L-arginine. L-ARG or D-ARG alone did not significantly modify the
      effect of KCl. The relaxations to KCl were significantly inhibited by omega
      conotoxin (omega-conotoxin; 0.1 microM), a selective blocker of N-type calcium
      channels. Propranolol (0.1-1 microM), a nonselective blocker of beta-adrenergic
      receptors, prazosine (0.01-0.1 microM), a selective blocker of alpha(1)
      adrenergic receptors, phentolamine (0.1-1 microM), a nonselective blocker of
      adrenergic receptors, atropine, a selective blocker of muscarinic cholinergic
      receptors, and lidocaine (1-10 microM), a blocker of sodium channels, had no
      effect on KCl-evoked relaxations. Caffeine (500 microM), an intracellular calcium
      releasing agent, did not significantly modify the effect of KCl. In contrast,
      ruthenium red (100 microM), a selective blocker of ryanodine receptors
      (intracellular Ca(2+) channels), significantly inhibited these relaxations.
      Similarly, potassium channel blockers such as 4-aminopyridine (4-AP; 100 microM)
      and tetraethylammonium (TEA; 100 microM) caused a significant inhibition on
      relaxations to KCl. In addition, ouabain (100 microM), a specific blocker of
      Na(+)-K(+)-ATPase, also caused a significant inhibition on these relaxations. The
      results suggest that NO, Na(+)-K(+)-ATPase and potassium channels may have a role
      on relaxations induced by 40 mM KCl in the frog esophagus.

PMID- 19171135
TI  - Regulation of endothelin-1-induced interleukin-6 production by Ca2+ influx in
      human airway smooth muscle cells.
AB  - Endothelin-1 is considered to be an important mediator in the pathophysiology of
      asthma because it induces contraction, hypertrophy, and proliferation in airway
      smooth muscle cells as well as inflammatory responses in the airway. Airway
      smooth muscle cells have been suggested to contribute to airway inflammation in
      asthma by producing cytokines. Nevertheless, the role of intracellular Ca(2+)
      signal in cytokine production in human airway smooth muscle cells is still
      unclear. We investigated the mechanisms by which endothelin-1 induces production
      of interleukin (IL)-6, a pleiotropic cytokine, in primary cultured human airway
      smooth muscle cells. Levels of IL-6 protein and mRNA were significantly increased
      by endothelin-1 in dose- and time-dependent manners. Endothelin-1-induced IL-6
      production was markedly attenuated by EGTA and various Ca(2+) channel inhibitors
      such as 3,5-bis(trifluoromethyl)-1H-pyrazole derivative (BTP-2), 1-[beta-[3-(4
      methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride (SKF96365),
      and nifedipine. Endothelin-1-induced increases in intracellular Ca(2+)
      concentrations were significantly inhibited in Ca(2+)-free solution and by BTP-2,
      SKF96365, and nifedipine. The IL-6 synthesis was also inhibited by the
      extracellular signal-regulated kinase (ERK)1/2 inhibitor 1,4-diamino-2,3-dicyano
      1,4-bis(o-aminophenylmercapto)-butadiene ethanolate (U0126) and the p38 inhibitor
      4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole
      (SB203580), but not by the c-Jun NH2-terminal kinase inhibitor anthra[1,9-cd]
      pyrazol-6-(2H)-one (SP600125). Endothelin-1 significantly upregulated
      phosphorylation of ERK1/2 and p38 but blocking Ca(2+) influx pathways did not
      inhibit either upregulation. These findings demonstrate that endothelin-1-induced
      IL-6 synthesis in airway smooth muscle cells occurs via two parallel but
      independent events that include Ca(2+) influx and activation of ERK1/2 and p38.

PMID- 19171134
TI  - The effects of medial prefrontal cortex infusions of cocaine in a runway model of
      drug self-administration: evidence of reinforcing but not anxiogenic actions.
AB  - In previous work we have shown that rats running a straight alley for intravenous
      (i.v.) or intracerebroventricular (i.c.v.) injections of cocaine develop an
      ambivalence about entering the goal box that results from cocaine's mixed
      reinforcing and anxiogenic properties. What remains unclear is whether or not
      cocaine's opposing properties stem from actions on a common neuronal system or
      from dual actions on separate systems - one related to reward and another to
      anxiogenic responses. One way to address this question is to deliver cocaine into
      discrete brain areas as a means of assessing whether or not the positive and
      negative effects of the drug can be spatially dissociated. Given the putative
      role of mesocorticolimbic dopamine pathways in the mediation of cocaine
      reinforced behavior, the current study examined the cocaine-seeking behavior of
      rats permitted to run an alley once each day for bilateral medial prefrontal
      cortex microinjections of cocaine (0.0, 12.5, 25 or 50 microg/0.5 microl per
      side) delivered upon goal-box entry. The results demonstrated that undrugged
      animals are highly motivated to seek medial prefrontal cortex cocaine without any
      evidence of negative or anxiogenic effects at any dose. These results are
      therefore consistent with suggestions of a medial prefrontal cortex involvement
      in the reinforcing actions of cocaine, and indicate that the dual and opposing
      actions of the drug can be dissociated and hence may be mediated by the drug's
      actions on separate neuronal systems.

PMID- 19171136
TI  - Green tea (-)-epigallocatechin-3-gallate down-regulates VASP expression and
      inhibits breast cancer cell migration and invasion by attenuating Rac1 activity.
AB  - (-)-Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound from green tea
      that has been shown to have anti-tumor activities such as inhibiting adhesion,
      migration, and proliferation of tumor cells. However, the delicate mechanisms and
      signaling pathways underlying the potential anticancer effects of EGCG in breast
      cancer cells remain unclear. The goal of this study was to examine the effects of
      EGCG on the migration and invasion of MCF-7 cells and to identify the signaling
      pathway(s) underlying the cellular response to EGCG exposure. In a concentration
      dependent manner, EGCG decreased the migratory and invasive potential of MCF-7
      cells with a concomitant down-regulation of vasodilator-stimulated phosphoprotein
      (VASP) expression and Rac1 activity. Using specific siRNAs to block the
      expression of VASP and Rac1 in MCF-7 cells that were previously treated with
      epidermal growth factor (EGF), we demonstrated that the regulation of cell
      migration and invasion was associated with Rac1 activity and VASP expression. In
      addition, siRNA mediated knock-down of Rac1 decreased the amount of VASP
      expression at the mRNA level while VASP specific siRNA revealed no effect on the
      expression of Rac1 in MCF-7 cells. These findings suggest that the inhibitory
      effect of EGCG on MCF-7 cell migration and invasion may be produced by a down
      regulation of VASP expression via the Rac1 pathway.

PMID- 19171137
TI  - Embryonic vaccines against cancer: an early history.
AB  - Almost 100 years have passed since the seminal observations of Schone showing
      that vaccination of animals with fetal tissue would prevent the growth of
      transplantable tumors. Many subsequent reports have affirmed the general idea
      that immunologic rejection of transplantable tumors, as well as prevention of
      carcinogenesis, may be affected by vaccination with embryonic/fetal material.
      Following a decade of intense research on this phenomenon during approximately
      1964-1974, interest appears to have waned. This earlier experimental work may be
      particularly pertinent in view of the rising interest in so-called cancer stem
      cells. We believe that further work - perhaps involving the use of embryonic stem
      cells as immunogens - is warranted and that the results reviewed herein support
      the concept that vaccination against the appearance of cancers of all kinds is a
      real possibility.

PMID- 19171139
TI  - Functional analysis of spfD gene involved in DNA phosphorothioation in
      Pseudomonas fluorescens Pf0-1.
AB  - DNA phosphorothioation is widespread in many bacterial species. By homology
      analysis of the dnd gene cluster in Pseudomonas fluorescens Pf0-1, a spfBCDE gene
      cluster involved in DNA phosphorothioation was localized. Disruption of the spfD
      gene, a dndD homolog, caused the loss of the Dnd phenotype and demonstrated the
      involvement of spfD in DNA phosphorothioation in P. fluorescens Pf0-1. The ATPase
      activity of SpfD suggests that SpfD could hydrolyze ATP to provide the energy
      required in the DNA phosphorothioate modification process.

PMID- 19171138
TI  - Functional imaging in Huntington's disease.
AB  - Huntington's disease (HD) is a genetic brain disease characterized by loss of
      capacity in movement control, cognition, and emotional regulation over a period
      of about 30 years. Since it is well established that clinical impairments and
      brain atrophy can be detected decades prior to receiving a clinical diagnosis,
      functional neuroimaging efforts have gained momentum in HD research. In most
      brain disorders, there is accumulating evidence that the clinical manifestations
      of disease do not simply depend on the extent of tissue loss, but represent a
      complex balance among neuronal dysfunction, tissue repair, and circuitry
      reorganization. Based upon this premise, functional neuroimaging modalities may
      be more sensitive to the earliest changes in HD than are structural imaging
      approaches. For this review, PET and fMRI studies conducted in HD samples were
      summarized. Strengths and limitations of the utilization of functional imaging in
      HD are discussed and recommendations are offered to facilitate future research
      endeavors.

PMID- 19171140
TI  - Kaempferol is an estrogen-related receptor alpha and gamma inverse agonist.
AB  - Kaempferol is a dietary flavonoid that is thought to function as a selective
      estrogen receptor modulator. In this study, we established that kaempferol also
      functions as an inverse agonist for estrogen-related receptors alpha and gamma
      (ERRalpha and ERRgamma). We demonstrated that kaempferol binds to ERRalpha and
      ERRgamma and blocks their interaction with coactivator peroxisome proliferator
      activated receptor gamma coactivator-1alpha (PGC-1alpha). Kaempferol also
      suppressed the expressions of ERR-target genes pyruvate dehydrogenase kinase 2
      and 4 (PDK2 and PDK4). This evidence suggests that kaempferol may exert some of
      its biological effect through both estrogen receptors and estrogen-related
      receptors.

PMID- 19171141
TI  - A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic
      polypectomy.
AB  - BACKGROUND & AIMS: Limited data exist regarding the actual risk of developing
      advanced adenomas and cancer after polypectomy or the factors that determine
      risk. METHODS: We pooled individual data from 8 prospective studies comprising
      9167 men and women aged 22 to 80 with previously resected colorectal adenomas to
      quantify their risk of developing subsequent advanced adenoma or cancer as well
      as identify factors associated with the development of advanced colorectal
      neoplasms during surveillance. RESULTS: During a median follow-up period of 47.2
      months, advanced colorectal neoplasia was diagnosed in 1082 (11.8%) of the
      patients, 58 of whom (0.6%) had invasive cancer. Risk of a metachronous advanced
      adenoma was higher among patients with 5 or more baseline adenomas (24.1%;
      standard error, 2.2) and those with an adenoma 20 mm in size or greater (19.3%;
      standard error, 1.5). Risk factor patterns were similar for advanced adenomas and
      invasive cancer. In multivariate analyses, older age (P < .0001 for trend) and
      male sex (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.19-1.65) were
      associated significantly with an increased risk for metachronous advanced
      neoplasia, as were the number and size of prior adenomas (P < .0001 for trend),
      the presence of villous features (OR, 1.28; 95% CI, 1.07-1.52), and proximal
      location (OR, 1.68; 95% CI, 1.43-1.98). High-grade dysplasia was not associated
      independently with metachronous advanced neoplasia after adjustment for other
      adenoma characteristics. CONCLUSIONS: Occurrence of advanced colorectal neoplasia
      is common after polypectomy. Factors that are associated most strongly with risk
      of advanced neoplasia are patient age and the number and size of prior adenomas.

PMID- 19171143
TI  - Electronic clinical challenges and images in GI. An unusual cause of small bowel
      obstruction.

PMID- 19171142
TI  - Galectin-1 is a novel functional receptor for tissue plasminogen activator in
      pancreatic cancer.
AB  - BACKGROUND & AIMS: Tissue plasminogen activator (tPA) exerts many different
      functions in addition to its role in fibrinolysis. In pancreatic ductal
      adenocarcinoma (PDA), tPA is overexpressed and plays an important role in
      proliferation, invasion, and angiogenesis. tPA interaction with cell membrane
      receptors has been related to increased proteolytic activity and to signal
      transduction through nonenzymatic mechanisms. The aim was to analyze the role of
      galectin-1 (Gal-1), an endogenous lectin that also is overexpressed in PDA, as a
      new functional receptor for tPA. METHODS: Gal-1/tPA interaction was analyzed
      using surface plasmon resonance and pull-down assays. Pancreatic cells and tumors
      were used to study Gal-1 expression and localization by Western blot and
      immunostaining. Down-regulation of Gal-1 by small interference RNA was used to
      analyze the involvement of Gal-1/tPA interaction in extracellular signal
      regulated kinase 1/2 activation, cell proliferation, and invasion in pancreatic
      and fibroblastic cells. RESULTS: Gal-1/tPA interaction is direct, specific, and
      of high affinity. Gal-1 moderately increases the catalytic activity of tPA. High
      Gal-1 levels were detected in PDA cells in culture, where it concentrates at the
      migration front, and in tissues, where it is expressed in epithelial cells and in
      the stroma. Down-regulation of Gal-1 abolished the effects of tPA on
      extracellular signal-regulated kinase 1/2 activation, cell proliferation, and
      invasion, both in pancreatic and in tumor-derived fibroblasts. CONCLUSIONS: These
      findings support a new molecular mechanism by which Gal-1 interaction with tPA
      contributes to PDA progression involving both transformed epithelial cells and
      tumor fibroblasts.

PMID- 19171144
TI  - Striving for abstinence in alcoholic pancreatitis: act of humanity, economic
      necessity, or flogging a dead horse after all?

PMID- 19171147
TI  - Cirrhosis regression in chronic hepatitis C: an old tale with a new ending.

PMID- 19171146
TI  - Clinical challenges and images in GI. Floating abdominal mass.

PMID- 19171148
TI  - Electronic clinical challenges and images in GI. Unusual cause of obstructive
      jaundice in a pregnant woman.

PMID- 19171149
TI  - Food availability during migratory stopover affects testis growth and
      reproductive behaviour in a migratory passerine.
AB  - Long-distance migratory passerines initiate testicular recrudescence during
      spring migration to meet the demands of timely reproduction upon immediate
      arrival on the breeding grounds. The degree of testicular development is known to
      depend on environmental factors like stopover habitat quality; reproductive
      performance may be strongly impacted by testicular maturation upon arrival on the
      breeding grounds. We investigated the effect of stopover food availability on
      subsequent reproductive performance in garden warblers (Sylvia borin). Spring
      migration was simulated by repeated food deprivation and re-feeding to imitate
      the alternation of flight and stopover periods. During the two final stopover
      periods, males were either kept under ad libitum food (ad libitum males) or under
      limited food conditions (limited males). After simulated arrival in the breeding
      area, manipulation of previous stopover food availability resulted in
      significantly slower testicular recrudescence (p<0.001) and decreased plasma
      testosterone (p<0.01) in limited males compared to ad libitum males. Body mass
      change was not significantly different between the two groups (p=0.38). Limited
      males also exhibited reduced performance in reproductive behaviours employed in
      territorial and sexual contexts. Limited males had a longer 'freezing' interval
      (p<0.05) and decreased activity (p<0.01) when challenged with a live male decoy.
      In direct confrontation between limited and ad libitum males in the presence of a
      female, limited males exhibited significantly fewer behavioural traits in sexual
      context, i.e. directed to the female (p<0.001). Therefore, we suggest that
      conditions encountered during previous migratory stopover may affect subsequent
      annual reproductive success by influencing key reproductive behaviours.

PMID- 19171150
TI  - A unique phosphatidylinositol 4-phosphate 5-kinase is activated by ADP
      ribosylation factor in Plasmodium falciparum.
AB  - In eukaryotes, calcium signalling has been linked to hydrolysis of the
      phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). The final enzyme in the
      synthesis of this phosphoinositide, a Type I phosphatidylinositol 4-phosphate 5
      kinase (PIP5K), is activated by the small G protein ADP-ribosylation factor 1
      (ARF1). In mammals, the ARF-PIP5K pathway is a key regulator of cell motility,
      secretion and cell signalling. We report the characterisation of a unique,
      putative bifunctional PIP5K in the human malaria parasite Plasmodium falciparum.
      The protein comprises a C-terminal, functional PIP5K domain with catalytic
      specificity for phosphatidylinositol 4-phosphate. The recombinant enzyme is
      activated by ARF1 but not phosphatidic acid. The protein also incorporates an
      unusual N-terminal domain with potential helix-loop-helix EF-hand-like motifs
      that is a member of the neuronal calcium sensor family (NCS). Intriguingly, NCS-1
      has been shown to stimulate phosphatidylinositol 4-phosphate synthesis by
      activating mammalian and yeast phosphatidylinositol 4-kinase beta in vitro in a
      calcium-dependent manner. The unexpected physical attachment of an NCS-like
      domain to the plasmodial PIP5K might reflect a unique functional link between the
      calcium and PtdIns(4,5)P(2) pathways allowing modulation of PtdIns(4,5)P(2)
      production in response to changes in intracellular calcium concentrations within
      the parasite.

PMID- 19171151
TI  - Hemolytic assay for the measurement of functional human mannose-binding lectin: a
      modification to avoid interference from classical pathway activation.
AB  - Diagnostic assays for measurement of functional mannose-binding lectin (MBL) in
      serum are widely performed as part of immune status assessment. Classical pathway
      mediated complement activity can interfere in these functional MBL assays. Here
      we describe classical pathway interference incidentally occurring in a previously
      described hemolytic MBL assay and the modification of this assay to prevent this
      artifact by addition of anti-C1q antibodies. Classical pathway interference in
      functional MBL assays can and should be inhibited to prevent that MBL deficiency
      is overlooked and patients are misdiagnosed.

PMID- 19171152
TI  - Life stage-related differences in hardening and acclimation of thermal tolerance
      traits in the kelp fly, Paractora dreuxi (Diptera, Helcomyzidae).
AB  - It is widely appreciated that physiological tolerances differ between life
      stages. However, few studies have examined stage-related differences in
      acclimation and hardening. In addition, the behavioural responses involved in
      determining the form and extent of the short-term phenotypic response are rarely
      considered. Here, we investigate life stage differences in the acclimation and
      hardening responses of the survival of a standard heat shock (SHS) and standard
      low temperature (or cold) shock (SCS), and the crystallization temperature (or
      supercooling point, SCP) of adults and larvae of the sub-Antarctic kelp fly,
      Paractora dreuxi. These stages live in the same habitat, but differ substantially
      in their mobility and thus environmental temperatures experienced. Results showed
      that neither acclimation nor hardening affected the lower lethal limits in larvae
      or adults. Adults showed an increase in survival of upper lethal limits after low
      temperature acclimation, whilst larvae showed a consistent lack of response. The
      acclimationxhardening interaction significantly affected the SCP in adults, but
      no response to either acclimation or hardening was found in the larvae. This
      study further demonstrates the complexities of thermal tolerance responses in P.
      dreuxi.

PMID- 19171153
TI  - Evolution of generous cooperative norms by cultural group selection.
AB  - Evolution of cooperative norms is studied in a population where individual- and
      group-level selection are both in operation. Individuals play indirect
      reciprocity game within their group. Individuals are well informed about the
      previous actions and reputations, and follow second-order norms. Individuals are
      norm-followers, and imitate their successful group mates. In contrast to previous
      models where norms classify actions deterministically, we assume that norms
      determine only the probabilities of actions, and mutants can differ in these
      probabilities. The central question is how a selective cooperative norm can
      emerge in a population where initially only non-cooperative norms were present.
      It is shown that evolution leads to a cooperative state if generous cooperative
      strategies are dominant, although the "always defecting" and the "always
      cooperating"-like strategies remain stably present. The characteristics of these
      generous cooperative strategies and the presence of always defecting and always
      cooperating strategies are in concordance with experimental observations.

PMID- 19171154
TI  - The effective size of bryophyte populations.
AB  - Bryophytes with their dominant haploid stage conform poorly to the life cycles
      generally treated in population genetical models. Here we make a detailed
      analysis of what effective sizes bryophyte model populations have as a function
      of their breeding system. It is found that the effective size is rarely much
      smaller than the scored number of haploid gametophytic individuals, even when the
      limited number of diploids (sporophytes) formed is taken into account. The most
      severe decrease in effective size occurs when unisexual gametophytic females
      produce only a small number of fertile diploid sporophytes in male biased
      populations; this effect is due to the restricted sampling of male gametophytic
      individuals that then occurs. It is shown that the harmonic mean of diploid
      sporophytes formed per haploid gametophytic individuals is the relevant measure
      in these calculations and not the standard (and generally larger) arithmetic
      mean.

PMID- 19171155
TI  - The amplitudes of viral blips in HIV-1 infected patients treated with
      antiretroviral therapy are power-law distributed.
AB  - We previously reported that in patients treated with highly active antiretroviral
      therapy (HAART) who achieve viral load (VL) suppression, low fluctuations of
      viral load over the threshold of detection (viral blips) more than 4 weeks apart
      occur at random, with a frequency that does not change with longer times of
      observation. The etiology of viral blips is currently unknown, but viral blip
      frequency inversely correlates with the decay of the latent reservoir, whose
      stability has been proposed as the major hurdle to HIV eradication. We show here
      that the distribution of viral blip amplitudes observed in a group of 272
      patients successfully treated with highly active antiretroviral therapy appears
      to be power-law distributed. Such a distribution can be theoretically generated
      by randomly sampling the arrival of asynchronous and overlapping elementary
      pulses of viremia, with asymptotic exponential decay of kinetics, thus suggesting
      that the low fluctuations of viremia observed in patients during HAART treatment
      is, in part, a discrete phenomenon consistent with random activation of latently
      infected cells or release of virus and infected cells into the blood compartment
      from unknown sites of active viral replication.

PMID- 19171156
TI  - When the exception becomes the rule: the disappearance of limiting similarity in
      the Lotka-Volterra model.
AB  - We investigate the transition between limiting similarity and coexistence of a
      continuum in the competitive Lotka-Volterra model. It is known that there exist
      exceptional cases in which, contrary to the limiting similarity expectation, all
      phenotypes coexist along a trait axis. Earlier studies established that the
      distance between surviving phenotypes is in the magnitude of the niche width
      2sigma provided that the carrying capacity curve differs from the exceptional one
      significantly enough. In this paper we studied the outcome of competition for
      small perturbations of the exceptional (Gaussian) carrying capacity. We found
      that the average distance between the surviving phenotypes goes to zero when the
      perturbation vanishes. The number of coexisting species in equilibrium is
      proportional to the negative logarithm of the perturbation. Nevertheless, the
      niche width provides a good order of magnitude for the distance between survivors
      if the perturbations are larger than 10%. Therefore, we conclude that limiting
      similarity is a good framework of biological thinking despite the lack of an
      absolute lower bound of similarity.

PMID- 19171157
TI  - Italian verb inflection in Alzheimer dementia.
AB  - A group of 20 patients with probable Alzheimer disease (AD) and a control group
      were tested in a verb generation task, in a verb synonym task and several
      cognitive tests. Three types of verbs and novel verbs were presented in simple
      sentence frames, in two different conditions. In one condition participants were
      presented with the verb in the infinitive, providing information about the
      conjugation of the verb and the most likely type of past participle mapping
      required. The second was an ambiguous condition in which the suffix of the input
      verb did not provide any clue to the conjugation. The aim was to investigate if
      different types of verbs and input mapping affected patients' performance, and to
      what extent the deficit increased when the illness became more severe. Dependent
      measures were accuracy rates, rates of different morpho-phonological
      transformations and error type rates. Patients showed a more marked deficit in
      verb generation, when input was ambiguous. Correlation between the verb synonym
      test and accuracy in verb generation indicated that a deficit in lexical-semantic
      memory was partially responsible for impaired performance. Data suggest that
      patients maintained information about frequency distribution of different verb
      types and verb classes in each conjugation, but were impaired in operating
      complex phonological transformations.

PMID- 19171158
TI  - Navigational expertise may compromise anterograde associative memory.
AB  - Grey matter volume increases have been associated with expertise in a range of
      domains. Much less is known, however, about the broader cognitive advantages or
      costs associated with skills and their concomitant neuroanatomy. In this study we
      investigated a group of highly skilled navigators, licensed London taxi drivers.
      We replicated findings from previous studies by showing taxi drivers had greater
      grey matter volume in posterior hippocampus and less grey matter volume in
      anterior hippocampus compared to matched control subjects. We then employed an
      extensive battery of tests to investigate the neuropsychological consequences of
      being a skilled taxi driver. Their learning of and recognition memory for
      individual items was comparable with control subjects, as were working memory,
      retrograde memory, perceptual and executive functions. By contrast, taxi drivers
      were significantly more knowledgeable about London landmarks and their spatial
      relationships. However, they were significantly worse at forming and retaining
      new associations involving visual information. We consider possible reasons for
      this decreased performance including the reduced grey matter volume in the
      anterior hippocampus of taxi drivers, similarities with models of aging, and
      saturation of long-term potentiation which may reduce information-storage
      capacity.

PMID- 19171159
TI  - Predation threat exerts specific effects on rat maternal behaviour and anxiety
      related behaviour of male and female offspring.
AB  - Differences in the rate of maternal behaviours received by rodent offspring are
      associated with differential programming of molecular and behavioural components
      of anxiety and stress-related functions. To determine the degree to which
      maternal behaviours are sensitive to environmental conditions, Long-Evans rat
      dams were exposed to the odour of a predator (cat) at two different time points
      during the first week postpartum. Exposure on the day of birth (DOB), but not the
      third day following birth, increased levels of maternal care in predator-exposed
      dams relative to dams exposed to a control condition across the first 5 days post
      partum. As adults, female offspring of dams exposed on DOB exhibited a less
      anxious phenotype in a novel open-field, spending more time in the center and
      less time displaying thigmotaxis. In contrast, under the same conditions, male
      offspring showed the opposite behavioural response, consistent with an
      increasingly anxious phenotype. Results from a subsequent stressor test (response
      to a predator odour) were consistent with the notion that the rearing effects
      were specific to anxiety-related behaviours in offspring. Accordingly, we showed
      that rearing conditions did not affect GR mRNA or NGFI-A expression in the
      hippocampus of offspring or cross-fostered offspring. The dissociation between
      stress and anxiety, as well as the sex-specific alterations in behaviour, may
      reflect the specificity inherent to neural programming in the face of
      naturalistic early life conditions.

PMID- 19171161
TI  - Electrophile-induced generation of cyclic azomethine imines from steroidal delta
      alkenyl hydrazones.
AB  - Novel delta-alkenyl phenylhydrazones were synthesized in both the estrone and the
      13alpha-estrone series. Electrophile-induced cyclizations of alkenyl
      phenylhydrazones with phenylselenyl bromide furnished cyclic iminium salts, via
      attack of the imino nitrogen atom on the intermediate seleniranium ion. Hydride
      reduction of the iminium salts led to novel aminophenyl-substituted aza-D
      homoestrones. The structures of the new products were determined by NMR (one- and
      two-dimensional) and MALDI-MS techniques, with C(70) fullerenes as matrix in the
      latter case.

PMID- 19171162
TI  - Paradoxical fusion of two images and depth perception with a squinting eye.
AB  - Some strabismic patients with inconstant squint can fuse two images in a single
      eye, and experience lustre and depth. One of these images is foveal and the other
      extrafoveal. Depth perception was tested on 30 such subjects. Relief was
      perceived mostly on the fixated image. Camouflaged continuous surfaces
      (hemispheres, cylinders) were perceived as bumps or hollows, without detail.
      Camouflaged rectangles could not be separated in depth from the background, while
      their explicit counterparts could. Slanted bars were mostly interpreted as
      frontoparallel near or remote bars. Depth responses were more frequent with
      stimuli involving inward rather than outward disparities, and were then heavily
      biased towards "near" judgements. All monocular fusion effects were markedly
      reduced after the recovery of normal stereoscopic vision following an orthoptic
      treatment. The depth effects reported here may provide clues on what stereoscopic
      pathways may or may not accomplish with incomplete retinal and misleading
      vergence information.

PMID- 19171160
TI  - Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive
      steroids in human and rat serum.
AB  - The 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone,
      deoxycorticosterone, dehydroepiandrosterone and testosterone enhance GABAergic
      neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory
      effects. Despite substantial information on the progesterone derivative
      (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha,5alpha-THP, allopregnanolone),
      the physiological significance of the other endogenous GABAergic neuroactive
      steroids has remained elusive. Here, we describe the validation of a method using
      gas chromatography-mass spectrometry to simultaneously identify serum levels of
      the eight 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone,
      deoxycorticosterone, dehydroepiandrosterone and testosterone. The method shows
      specificity, sensitivity and enhanced throughput compared to other methods
      already available for neuroactive steroid quantification. Administration of
      pregnenolone to rats and progesterone to women produced selective effects on the
      3alpha,5alpha- and 3alpha,5beta-reduced neuroactive steroids, indicating
      differential regulation of their biosynthetic pathways. Pregnenolone
      administration increased serum levels of 3alpha,5alpha-THP (+1488%, p<0.001),
      (3alpha,5alpha)-3,21-dihydroxypregnan-20-one (3alpha,5alpha-THDOC, +205%,
      p<0.01), (3alpha,5alpha)-3-hydroxyandrostan-17-one (3alpha,5alpha-A, +216%,
      p<0.001), (3alpha,5alpha,17beta)-androstane-3,17-diol (3alpha,5alpha-A-diol,
      +190%, p<0.01). (3alpha,5beta)-3-hydroxypregnan-20-one (3alpha,5beta-THP) and
      (3alpha,5beta)-3-hydroxyandrostan-17-one (3alpha,5beta-A) were not altered, while
      (3alpha,5beta)-3,21-dihydroxypregnan-20-one (3alpha,5beta-THDOC) and
      (3alpha,5beta,17beta)-androstane-3,17-diol (3alpha,5beta-A-diol) were increased
      from undetectable levels to 271+/-100 and 2.4+/-0.9 pg+/-SEM, respectively (5/8
      rats). Progesterone administration increased serum levels of 3alpha,5alpha-THP
      (+1806%, p<0.0001), 3alpha,5beta-THP (+575%, p<0.001), 3alpha,5alpha-THDOC
      (+309%, p<0.001). 3alpha,5beta-THDOC levels were increased by 307%, although this
      increase was not significant because this steroid was detected only in 3/16
      control subjects. Levels of 3alpha,5alpha-A, 3alpha,5beta-A and pregnenolone were
      not altered. This method can be used to investigate the physiological and
      pathological role of neuroactive steroids and to develop biomarkers and new
      therapeutics for neurological and psychiatric disorders.

PMID- 19171163
TI  - Adrenalectomy potentiates the antinociceptive effects of calcium channel
      blockers.
AB  - Calcium channel blockers can modulate the nociceptive threshold. However, the
      underlying mechanism(s), especially the role of hypothalamic-pituitary-adrenal
      (HPA) axis, on this effect has not yet been clarified. In the present study we
      investigated the analgesic effect of verapamil, diltiazem and nimodipine in
      intact and adrenalectomized (ADX) male rats and also measured the effect of these
      drugs on HPA function. The tail-flick and hot-plate tests were used to assess the
      nociceptive threshold before and 15, 30, 60 and 120 min after drug
      administration. Corticosterone level was measured by radioimmunoassay as a marker
      of HPA function. Our results showed that these drugs could elicit antinociceptive
      effects which were more prominent in the hot-plate than in the tail-flick tests.
      Following the exclusion of adrenal glands these drugs showed stronger analgesic
      effects. Acute administration of verapamil, diltiazem and nimodipine produced
      significant decrease in plasma corticosterone level that was more prominent by
      nimodipine. In conclusion, the results of our study show that the HPA function
      has an important role in the antinociceptive effect of calcium channel blockers.

PMID- 19171164
TI  - Time-dependent retrograde amnesic effects of muscimol on conditioned taste
      aversion extinction.
AB  - We explored how stimulation of GABA(A) receptors at different times during
      conditioned taste aversion (CTA) acquisition or extinction influenced extinction.
      In Experiment 1, rats acquired a CTA to 0.3% saccharin-flavored water (SAC) when
      it followed an injection of lithium chloride (LiCl; 81.0 mg/kg, i.p.). Following
      conditioning, rats received extinction training in which the GABA(A) agonist
      muscimol (1.0 mg/kg, i.p.), or control (saline) injections, were administered
      either before or after each extinction trial. Muscimol hindered extinction when
      administered after extinction trials. Muscimol's inhibitory effects may have
      impeded extinction learning by disrupting synaptic mechanisms required to
      consolidate information experienced during extinction training. In Experiment 2,
      we studied the effects of muscimol on CTA acquisition and subsequent extinction.
      Rats received muscimol (1.0 mg/kg, i.p.) either before or after CTA conditioning
      trials. Following CTA acquisition, all rats were given CTA extinction training
      without muscimol administration. All groups developed CTA, but the group that
      received muscimol before CTA conditioning trials extinguished rapidly in
      comparison to other treatment groups. Differences between muscimol's effects on
      CTA conditioning and CTA extinction indicate that fear conditioning and
      extinction involve, to some degree, different neuronal mechanisms.

PMID- 19171166
TI  - The role of formins in filopodia formation.
AB  - Filopodia are highly dynamic cell-surface protrusions used by cells to sense
      their external environment. At the core of the filopodium is a bundle of actin
      filaments. These give form to the filopodia and also drive the cycle of
      elongation and retraction. Recent studies have shown that two very different
      actin nucleating proteins control the formation of filopodial actin filaments -
      Arp2/3 and Formins. Although the actin filaments produced by these two nucleators
      have very different structures and properties, recent work has begun to piece
      together evidence for co-operation between Arp2/3 and formins in filopodia
      formation, leading to a deeper understanding of these sensory organelles.

PMID- 19171165
TI  - Nucleotide signaling and cutaneous mechanisms of pain transduction.
AB  - Sensory neurons that innervate the skin provide critical information about
      physical contact between the organism and the environment, including information
      about potentially-damaging stimuli that give rise to the sensation of pain. These
      afferents also contribute to the maintenance of tissue homeostasis, inflammation
      and wound healing, while sensitization of sensory afferents after injury results
      in painful hypersensitivity and protective behavior. In contrast to the
      traditional view of primary afferent terminals as the sole site of sensory
      transduction, recent reports have lead to the intriguing idea that cells of the
      skin play an active role in the transduction of sensory stimuli. The search for
      molecules that transduce different types of sensory stimuli (mechanical, heat,
      chemical) at the axon terminal has yielded a wide range of potential effectors,
      many of which are expressed by keratinocytes as well as neurons. Emerging
      evidence underscores the importance of nucleotide signaling through P2X
      ionotropic and P2Y metabotropic receptors in pain processing, and implicates
      nucleotide signaling as a critical form of communication between cells of the
      skin, immune cells and sensory neurons. It is of great interest to determine
      whether pathological changes in these mechanisms contribute to chronic pain in
      human disease states such as complex regional pain syndrome (CRPS). This review
      discusses recent advances in our understanding of communication mechanisms
      between cells of the skin and sensory axons in the transduction of sensory input
      leading to pain.

PMID- 19171167
TI  - Event-related potentials with the Stroop colour-word task: timing of semantic
      conflict.
AB  - Event-Related Potentials (ERPs) elicited by congruent and incongruent colour-word
      stimuli of a Stroop paradigm, in a task in which participants were required to
      judge the congruence/incongruence of the two dimensions of the stimuli, were
      recorded in order to study the timing of the semantic conflict. The reaction time
      to colour-word incongruent stimuli was significantly longer than the reaction
      time to congruent stimuli (the Stroop effect). A temporal Principal Components
      Analysis was applied to the data to identify the ERP components. Three positive
      components were identified in the 300-600 ms interval in response to the
      congruent and incongruent stimuli: First P3, P3b and PSW. The factor scores
      corresponding to the First P3 and P3b components were significantly smaller for
      the incongruent stimuli than for the congruent stimuli. No differences between
      stimuli were observed in the factor scores corresponding to the PSW or in the ERP
      latencies. We conclude that the temporal locus of the semantic conflict, which
      intervenes in generating the Stroop effect, may occur within the time interval in
      which the First P3 and P3b components are identified, i.e. at approximately 300
      450 ms post-stimulus. We suggest that the semantic conflict delays the start of
      the response selection process, which explains the longer reaction time to
      incongruent stimuli.

PMID- 19171168
TI  - Cellular uptake of self-assembled cationic peptide-DNA complexes: multifunctional
      role of the enhancer chloroquine.
AB  - A small library of carriers consisting of various combinations of the cell
      penetrating peptide TAT, the SV40 Large T protein nuclear localisation signal
      (NLS) and a cationic dendrimer of 7 lysine residues (DEN) was synthesised and
      each member was tested for its ability to deliver exogenous DNA to human HeLa
      cells. We found that the TAT peptide was essential, but not sufficient for
      efficient uptake of exogenous DNA. The addition of either NLS or DEN
      significantly enhanced uptake and expression with the most active carrier
      consisting of the TAT, NLS and DEN peptides. For those peptides that facilitated
      DNA uptake, the complexes were targeted to intracellular compartments that
      required incubation with a fusogenic agent such as chloroquine before gene
      expression was observed. However, our data suggest that chloroquine did not
      enhance expression solely by promoting endosomal release since a fusogenic
      peptide derived from the influenza virus haemagglutinin protein did not improve
      gene expression. Chloroquine was found to protect DNA from degradation and
      enhance transcription of DNA bound to the respective carriers. Our results
      demonstrate that multi-component peptide-based gene carriers can be designed to
      deliver exogenous DNA. The actions of lysosomotropic agents such as chloroquine
      reveal the multifactorial properties required for carriers used in non-viral gene
      delivery.

PMID- 19171169
TI  - Invertebrate neuropeptides IX.

PMID- 19171170
TI  - The trinity of Ca2+ sources for the exocytotic glutamate release from astrocytes.
AB  - Astrocytes can exocytotically release the transmitter glutamate. Increased
      cytosolic Ca(2+) concentration is necessary and sufficient in this process. The
      source of Ca(2+) for the Ca(2+)-dependent exocytotic release of glutamate from
      astrocytes predominately comes from endoplasmic reticulum (ER) stores with
      contributions from both inositol 1,4,5-trisphosphate- and ryanodine/caffeine
      sensitive stores. An additional source of Ca(2+) comes from the extracellular
      space via store-operated Ca(2+) entry due to the depletion of ER stores. Here
      transient receptor potential canonical type 1 containing channels permit entry of
      Ca(2+) to the cytosol, which can then be transported by the store-specific Ca(2+)
      ATPase to (re)fill ER. Mitochondria can modulate cytosolic Ca(2+) levels by
      affecting two aspects of the cytosolic Ca(2+) kinetics in astrocytes. They play a
      role in immediate sequestration of Ca(2+) during the cytosolic Ca(2+) increase in
      stimulated astrocytes as a result of Ca(2+) entry into the cytosol from ER stores
      and/or extracellular space. As cytosolic Ca(2+)declines due to activity of pumps,
      such as the smooth ER Ca(2+)-ATPase, free Ca(2+) is slowly released by
      mitochondria into cytosol. Taken together, the trinity of Ca(2+) sources, ER,
      extracellular space and mitochondria, can vary concentration of cytosolic Ca(2+)
      which in turn can modulate Ca(2+)-dependent vesicular glutamate release from
      astrocytes. An understanding of how these Ca(2+) sources contribute to glutamate
      release in (patho)physiology of astrocytes will provide information on astrocytic
      functions in health and disease and may also open opportunities for medical
      intervention.

PMID- 19171171
TI  - vGLUT2 heterozygous mice show more susceptibility to clonic seizures induced by
      pentylenetetrazol.
AB  - Glutamate, the most abundant excitatory neurotransmitter in the central nervous
      system, is well known to be implicated in epileptic seizures. Therefore,
      impairments in glutamate transport could have an involvement in the mechanism of
      epileptogenesis. The uptake of glutamate into synaptic vesicles is mediated by
      vesicular glutamate transporters (vGLUTs). There are three known vGLUT isoforms,
      vGLUT1-3. In this study, we are particularly interested in the vGLUT2 isoform. We
      investigated the possible role of vGLUT2 in pentylenetetrazol (PTZ)-induced
      seizure generation. Seizure threshold of PTZ was compared in vGLUT2 heterozygous
      knock out (HET) and wild type (WT) mice. In comparison with their WT littermates
      a lower dose of PTZ was needed in the vGLUT2 HET mice until the onset of the
      first myoclonic jerk. The threshold for PTZ-induced clonic seizure activity was
      also lower in the vGLUT2 HET mice. These results indicate, for the first time,
      that vGLUT2 is likely involved in the epileptogenesis of generalized seizures.

PMID- 19171172
TI  - Effects of chronic mild stress on the oxidative parameters in the rat brain.
AB  - Major depression is characterized for symptoms at the psychological, behavioral
      and physiological levels. The chronic mild stress model has been used as an
      animal model of depression. The consumption of sweet food, locomotor activity,
      body weight, lipid and protein oxidation levels and superoxide dismutase and
      catalase activities in the rat hippocampus, prefrontal cortex and cortex were
      assessed in rats exposed to chronic mild stress. Our findings demonstrated a
      decrease on sweet food intake, no effect on locomotor activity, lack of body
      weight gain, increase in protein (prefrontal, hippocampus, striatum and cortex)
      and lipidic peroxidation (cerebellum and striatum), and an increase in catalase
      (cerebellum, hippocampus, striatum, cortex) and a decrease in superoxide
      dismutase activity (prefrontal, hippocampus, striatum and cortex) in stressed
      rats. In conclusion, our results support the idea that stress produces oxidants
      and an imbalance between superoxide dismutase and catalase activities that
      contributes to stress-related diseases, such as depression.

PMID- 19171173
TI  - A modified epitope identified for generation and monitoring of PSA-specific T
      cells in patients on early phases of PSA-based immunotherapeutic protocols.
AB  - Efficacy of vaccination in cancer patients on immunotherapeutic protocols can be
      difficult to evaluate. The aim of this study was therefore to identify a single
      natural or modified epitope in prostate-specific antigen (PSA) with the ability
      to generate high levels of PSA-specific T cells to facilitate monitoring in
      patients after vaccination against prostate cancer. To the best of our knowledge,
      this study describes for the first time the peptide specificity of T cells
      stimulated by endogenously processed PSA antigen. The peptide specificity of HLA
      A*0201-restricted CD8(+) T cells against human and rhesus PSA was investigated
      both in vivo after DNA vaccination in HLA-A*0201-transgenic mice and in vitro
      after repetitive stimulation of human T cells with DNA-transfected human
      dendritic cells (DCs). One of seven native PSA peptides, psa53-61, was able to
      activate high levels of PSA-specific CD8(+) T cells in HLA-A*0201-transgenic mice
      after PSA DNA vaccination. Psa53-61 was also the only peptide that induced human
      T cells to produce IFNgamma after stimulation with PSA transfected DCs, however
      not in all donors. Therefore, plasmids encoding modified epitopes in predicted
      HLA-A*0201 sequences were constructed. One of these modified PSA plasmids
      consistently induced IFNgamma producing CD8(+) T cells to the corresponding
      modified peptide as well as to the corresponding native peptide, in all murine
      and human T cell cultures. This study demonstrates a novel concept of introducing
      a modified epitope within a self-tumor antigen, with the purpose of eliciting a
      reliable T cell response from the non-tolerized immune repertoire, to facilitate
      monitoring of vaccine efficacy in cancer patients on immunotherapeutic protocols.
      The purpose of such a modified epitope is thus not to induce therapeutically
      relevant T cells but rather to, in case of weak or divergent T cell responses to
      self antigens/peptides, help answer questions about efficacy of vaccine delivery
      and about the possibility to induce immune responses in the selected and often
      immunosuppressed cancer patients.

PMID- 19171174
TI  - Clinical effectiveness of 23-valent pneumococcal polysaccharide vaccine against
      pneumonia in middle-aged and older adults: a matched case-control study.
AB  - The 23-valent polysaccharide pneumococcal vaccine is currently recommended in
      elderly and high-risk adults. Its efficacy against invasive pneumococcal disease
      has been demonstrated, but its effectiveness in preventing pneumonia remains
      uncertain. This study assessed the clinical effectiveness of vaccination against
      pneumonia among middle-aged and older adults. We conducted a population-based
      case-control study including 304 case patients over 50 years old with
      radiographically confirmed pneumococcal pneumonia (94 bacteremic and 210
      nonbacteremic cases) and 608 outpatient control subjects (matched by primary care
      centre, age, sex and risk stratum). Adjusted odds ratios (ORs) for vaccination
      were calculated using conditional logistic regression, controlling for underlying
      conditions. Vaccine effectiveness against all pneumococcal pneumonia was 48% (OR:
      0.52; 95% confidence interval [CI]: 0.37-0.73). Vaccination was effective against
      bacteremic cases (OR: 0.34; 95% CI: 0.27-0.66) as well as nonbacteremic cases
      (OR: 0.58; 95% CI: 0.39-0.86). Vaccine effectiveness was highest against
      bacteremic infections caused by vaccine types (OR: 0.24; 95% CI: 0.09-0.66).
      These findings confirm the effectiveness of the vaccine against invasive disease,
      but they also support the benefit of vaccination in preventing nonbacteremic
      pneumococcal pneumonia.

PMID- 19171175
TI  - Pneumococcal antibodies in a child with type 14 pneumococcal conjugate vaccine
      failure.
AB  - We measured the concentration, opsonic activity, and avidity of serotype-specific
      serum antibodies in a pneumococcal conjugate vaccine (PnCRM7) efficacy trial
      participant who contracted serotype 14 pneumococcal bacteremia following dose 3
      of PnCRM7. Controls included 18 PnCRM7- and 10 MnCC-vaccinated children without
      invasive pneumococcal disease (IPD). The child with vaccine failure had
      4.98mcg/mL of serotype 14 antibodies 10 days before disease onset; these
      antibodies had greater opsonic activity and lower avidity than those of control
      PnCRM7 recipients. The child had no booster response to a fourth dose of PnCRM7
      for most vaccine serotypes. We conclude that antibody concentration, functional
      activity and avidity do not predict individual protection against IPD, and
      immunological correlates of protection are only useful at the population level.

PMID- 19171176
TI  - Brain GABA levels in patients with bipolar disorder.
AB  - PURPOSE: A growing body of research supports an important role for GABA in the
      pathophysiology of bipolar and other mood disorders. The purpose of the current
      study was to directly examine brain GABA levels in a clinical sample of bipolar
      patients. GENERAL METHODS: We used magnetic resonance spectroscopy (MRS) to
      examine whole brain and regional GABA, glutamate and glutamine in 13 patients
      with bipolar disorder compared to a matched group of 11 healthy controls.
      FINDINGS: There were no significant differences in GABA, glutamate or glutamine
      between patients and controls. CONCLUSIONS: Further research is needed to better
      characterize the GABAergic and glutamatergic effects of pharmacotherapy, anxiety
      comorbidity and clinical state in bipolar disorder.

PMID- 19171177
TI  - Behavioral and degeneration changes in the basal forebrain systems of aged rats:
      a quantitative study in the region of the basal forebrain after levo-acetyl
      carnitine treatments assessed by Abercrombie estimation.
AB  - One group of six male control rats [21 months old] and one group of six male rats
      of the same age, singularly stored in a cage, and treated with acetyl-l-carnitine
      HCl (ALCAR: 60 mg/kg/day/p.o.) for six months were tested in the spatial
      learning/memory Morris maze-water task and for atrophy and cell loss in seven
      myelo- and cytostructurally defined basal forebrain (BF) cholinergic regions
      [Gritti et al., 1993 J Comp Neurol 329: 438-457]. Coronal sections 25 mum thick
      were cut through the BF regions and processed every 200 mum for choline
      acetyltransferase (ChAT) immunohistochemistry. The ALCAR-treated rats had
      significantly shorter exit times on the Morris maze-water task test than the
      control rats (ANOVA-enzyme: F(1,39)=112.5, P=0.0001; sessions: F(3,39)=10.41,
      P=0.0001; interaction: F(3,39)=5.09, P=0.0044). Degenerative morphological
      changes in the BF ChAT-positive cells were observed in the control rats, but not
      in the treated animals, in: the diagonal band of Broca, the magnocellular
      preoptic nucleus, the olfactory tubercle, the substantia innominata, and the
      globus pallidus (ANOVA-enzyme: F(1,2)=14, P=0,0003; structures: F(6,7)=4,
      P=0,0018; interaction: F(6,7)=3, P=0,0043). In the diagonal band of Broca
      (P<0.0494) and in the magnocellular preoptic nucleus (P<0.0117) there were
      significantly fewer ChAT-positive neurons in the aged control rats than in the
      ALCAR-treated rats. These results demonstrate that in rats aged from 15 to 21
      months ALCAR treatment significantly attenuated spatial learning/memory
      impairment on the Morris maze-water task and also importantly reduced the
      degeneration in size and number of cholinergic cells in the BF.

PMID- 19171178
TI  - Dynein motor contributes to stress granule dynamics in primary neurons.
AB  - Mobilization and translation of mRNAs, two important events believed to involve
      stress granules (SGs), in neurons are important for their survival and
      activities. However, the formation and disassembly of SGs in neurons remains
      unclear. By using an arsenite-induced neuronal stress model of rat primary spinal
      cord neuron cultures, we demonstrate the formation of SGs that contain common SG
      components and RNAs in both stressed neuronal cell bodies and their neurites. By
      employing small interfering RNA (siRNA) knockdown, we discovered that dynein
      motor subunit localizes in SG, and is important for SG assembly in neurons. Under
      stress, dynein motor subunit also facilitates translational repression and
      enhances the formation and integrity of SG in neurons. By blocking the energy
      source of dynein motor, both the formation and disassembly of SG are attenuated.
      These findings demonstrate, for the first time, that dynein motor complex plays a
      critical role in the dynamics of neuronal SGs, as well as translation of certain
      mRNAs.

PMID- 19171179
TI  - In inflammatory reactive astrocytes co-cultured with brain endothelial cells
      nicotine-evoked Ca(2+) transients are attenuated due to interleukin-1beta release
      and rearrangement of actin filaments.
AB  - The aim of this study was to investigate whether nicotine acetylcholine receptors
      (nAChRs) are expressed in a more pronounced way in astrocytes co-cultured with
      microvascular endothelial cells from adult rat brain, compared with monocultured
      astrocytes, as a sign of a more developed signal transduction system. Also
      investigated was whether nicotine plays a role in the control of
      neuroinflammatory reactivity in astrocytes. Ca(2+) imaging experiments were
      performed using cells loaded with the Ca(2+) indicator Fura-2/AM. Co-cultured
      astrocytes responded to lower concentrations of nicotine than did monocultured
      astrocytes, indicating that they are more sensitive to nicotine. Co-cultured
      astrocytes also expressed a higher selectivity for alpha7nAChR and alpha4/beta2
      subunits and evoked higher Ca(2+) transients compared with monocultured
      astrocytes. The Ca(2+) transients referred to are activators of Ca(2+)-induced
      Ca(2+) release from intracellular stores, both IP(3) and ryanodine, triggered by
      influx through receptor channels. The nicotine-induced Ca(2+) transients were
      attenuated after incubation with the inflammatory mediator lipopolysaccharide
      (LPS), but were not attenuated after incubation with the pain-transmitting
      peptides substance P and calcitonin-gene-related peptide, nor with the infection
      and inflammation stress mediator, leptin. Furthermore, LPS-induced release of
      interleukin-1beta (IL-1beta) measured by enzyme-linked immunosorbent assay
      (ELISA) was more pronounced in co-cultured versus monocultured astrocytes.
      Incubation with both LPS and IL-1beta further attenuated nicotine-induced Ca(2+)
      response. We also found that LPS and IL-1beta induced rearrangement of the F
      actin filaments, as measured with an Alexa488-conjugated phalloidin probe. The
      rearrangements consisted of increases in ring formations and a more dispersed
      appearance of the filaments. These results indicate that there is a connection
      between a dysfunction of nicotine Ca(2+) signaling in inflammatory reactive
      astrocytes and upregulation of IL-1beta and the rearrangements of actin filaments
      in the cells.

PMID- 19171180
TI  - Sciatic nerve conditioned medium depleted of pro-NGF modulates sodium currents
      and neurite outgrowth in PC12 cells.
AB  - Excitability and axon/dendrite specification are the most distinctive features in
      the establishment of neuronal polarization. Conditioned medium from rat sciatic
      nerve (CM) induced a neuronal-like morphology in PC12 cells. Here we show that CM
      neuritogenic activity is limited to the induction of dendrites in PC12 cells.
      However, treatment of these cells with CM in combination with a generic inhibitor
      for tyrosine kinase receptors (k252a) promoted the enhancement of neurite length,
      development of axons and induction of sodium currents. On the other hand,
      specific inhibition of TrkA and p75(NTR) receptors in CM-treated cells reduced
      the neurite length in comparison with cells treated only with CM, although the
      effect over the induction of sodium currents was continuously observed. These
      results suggested that CM had some components that, even though are able to start
      the morphological cell differentiation and produce short neurites (likely acting
      through TrkA and p75(NTR)), can restrain further neurite extension. Depletion of
      pro-NGF isoforms from CM produced a similar effect as the exerted by k252a, TrkA
      and p75(NTR) receptor inhibitors in CM-treated cells, inducing the elicitation of
      sodium currents. These results suggested that the effect of CM might be mediated
      through pro-NGF. The difference between the results obtained with the generic
      inhibitor for Trk receptors and the specific inhibitors for TrkA and p75(NTR)
      receptors in CM-treated cells, suggested that alternative pathways could be used
      to regulate neurite elongation, axon specification and sodium currents in PC12
      cells. These findings represent important clues to improve the understanding of
      the initiation of neuronal polarity.

PMID- 19171181
TI  - Sex differences in contextual fear conditioning are associated with differential
      ventral hippocampal extracellular signal-regulated kinase activation.
AB  - Although sex differences have been reported in hippocampal-dependent learning and
      memory, including contextual fear memories, the underlying molecular mechanisms
      contributing to such differences are not well understood. The present study
      examined the extent to which sex differences in contextual fear conditioning are
      related to differential activation of the extracellular signal-regulated
      kinase/mitogen-activated protein kinase (ERK/MAPK), a protein kinase critically
      involved in memory formation. We first show that male rats exhibit more long-term
      retention of contextual fear conditioning than female rats. During a tone test,
      females spent more time freezing than males, although both sexes exhibited robust
      retention of auditory fear learning. Using Western blot analysis, we then show
      that phosphorylated ERK levels in ventral, but not dorsal, hippocampus are higher
      in males than females, relative to same-sex controls, 60 minutes after fear
      conditioning. Post-conditioning increases in ERK activation were observed in the
      amygdala in both males and females, suggesting a selective effect of sex on
      hippocampal ERK activation. Together, these findings suggest that differential
      activation of the ERK signal transduction pathway in male and female rats,
      particularly in the ventral hippocampus, is associated with sex differences in
      contextual fear.

PMID- 19171183
TI  - Skull lichens: a curious chapter in the history of phytotherapy.
AB  - Lichens growing on skulls were known in late medieval times as usnea or moss of a
      dead man's skull and were recommended as highly beneficial in various diseases.
      They were, in addition, the main ingredient of Unguentum armariun, a liniment
      used in a curious medical practice: the magnetic cure of wounds. We can place
      this chapter of the history of phytotherapy within the wider cultural context of
      the period, which saw the definition of nature become increasingly more fluid and
      open to a variety of novel interpretations.

PMID- 19171182
TI  - Gray matter metabolism in acute and chronic hydrocephalus.
AB  - Although hydrocephalus is usually considered a disorder of periventricular white
      matter, disturbance of gray matter is probably also involved. However, so far
      gray matter metabolism has not been studied in experimental hydrocephalus using
      high resolution in vivo magnetic resonance spectroscopy (MRS). Therefore 15 rats
      were made hydrocephalic by injection of 0.1 ml kaolin into the cisterna magna,
      whereas 10 sham-operated rats served as controls. (1)H MRS and magnetic resonance
      imaging were performed longitudinally in acute hydrocephalus 2 and 4 weeks after
      kaolin treatment and in chronic hydrocephalus after 6 weeks. Volumes of interest
      included the gray matter regions cortex, thalamus and hippocampus. In
      hydrocephalic animals, (1)H MRS revealed decreased glutamate levels in all
      examined areas at all time points. Moreover, in acute hydrocephalus disturbances
      were noted in the hippocampus with decreased concentrations of N-acetyl
      aspartate, creatine, inositol and taurine, and in the cortex with decreased
      taurine levels. A clear lactate peak was detected in CSF spectra from
      hydrocephalic rats. In addition, T2-weighted images showed increase of free water
      in the hippocampus. It can be concluded that glutamate metabolism is deranged in
      gray matter in acute and chronic hydrocephalus in rats. If confirmed in humans,
      early detection of glutamatergic disturbances and lactate accumulation using in
      vivo(1)H MRS might serve as an indication for surgical treatment of hydrocephalus
      before irreversible neuronal damage develops.

PMID- 19171184
TI  - The ATTCT repeats of spinocerebellar ataxia type 10 display strong nucleosome
      assembly which is enhanced by repeat interruptions.
AB  - Nucleosome packaging influences many aspects of DNA metabolism such as
      replication, repair and transcription, and via this link likely has further
      downstream effects on genome stability. The instability and expansion of
      repetitive sequences is associated with at least 42 human diseases, yet the
      molecular conditions contributing to repeat instability have remained largely
      undetermined. Previously we showed strong nucleosome formation on CAG repeats
      associated with spinocerebellar ataxia type 1 and very weak formation on CGG
      repeats associated with fragile X syndrome, and that interruption of these repeat
      tracts made the DNA behave more like random sequences. In this study, we
      determined nucleosome formation on pure and interrupted ATTCT pentanucleotides
      associated with spinocerebellar ataxia type 10 (SCA10). We report strong
      nucleosome formation on ATTCT repeats, like CAG tracts. Surprisingly, in contrast
      to the effect of interruptions on other repeat sequences, interruptions in the
      expanded ATTCT tracts further strengthened assembly with hyperacetylated histones
      under physiological conditions with NAP-1. These differences may contribute to
      phenotypic variation seen between families having pure and interrupted SCA10
      repeats, as well as the overall genetic instability at the SCA10 locus.

PMID- 19171185
TI  - Ethnoveterinary knowledge in pastoral Karamoja, Uganda.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The people of Karamoja of northern Uganda chiefly
      rely on ethnoveterinary knowledge (EVK) to control common livestock health
      problems. In spite of cattle's central role in Karamojong culture and
      livelihoods, there has been no systematic recording of their ethnoveterinary
      plant-based cures to date. AIM OF STUDY: To document the remedies used to treat
      livestock diseases, their preparation and administration. METHODS: Data were
      collected using semi-structured interviews, guided questionnaires, group
      discussions, direct observations and collection trips. RESULTS: We present
      information on 209 plant species and 18 non-plant materials. Plant species are
      distributed over 116 genera and 54 families. The most common medicinal use was
      treatment against anaplasmosis. Balanites aegyptiacus, Carissa spinarum,
      Warburgia salutaris and Harrisonia abyssinica had the most uses of all species.
      All different plant parts were used; bark and underground parts were exploited
      more frequently than other plant parts. Most remedies listed used a single
      ingredient, typically soaked in water; only 12.8% remedies used multiple plants.
      The route of administration was primarily oral followed by topical applications.
      Almost all plants are collected from the wild; none of the few cultivated plants
      used had been planted for medicinal purposes. CONCLUSIONS: The pastoralists in
      the study site possess a wealth of EVK which they use to maintain animal health.
      Their rich knowledge and high diversity of plants were recorded here for the
      first time.

PMID- 19171186
TI  - Proapoptotic and prepulse inhibition (PPI) disrupting effects of Hypericum
      perforatum in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: St. John's wort extract is commonly used as a
      wound healing, anti-inflammatory, anxiolytic, diuretic, antibiotic, antiviral and
      cancer chemoprotective agent. It also has nootropic and/or antiamnestic effects.
      AIM OF THE STUDY: Prepulse inhibition (PPI) of startle response is a valuable
      paradigm for sensorimotor gating processes. A previous study indicated that
      single administration of St. John's wort extract (500 mg/kg) caused PPI
      disruption in rats. The effect of antiamnestic doses of the extract on PPI has
      not been investigated despite the coexistence of impaired memory and PPI deficit
      in some neurological disorders. MATERIALS AND METHODS: The effects of acute (500
      mg/kg) and chronic (200mg/kg for 3 days) administration of St. John's wort
      extract were investigated for its antiamnestic activity. The effects of
      administration of the antiamnestic dose of the extract and hyperforin, its main
      active component, were tested on PPI of an acoustic startle response in rats.
      This study also investigated the proapoptotic effect of hyperforin in animals,
      demonstrating PPI deficit, by electrophoresis of DNA isolated from selected brain
      areas. RESULTS: Disruption of PPI resulted after treatment of rats with an
      antiamnestic dose of the extract (200mg/kg for 3 days) and with hyperforin. Gel
      electrophoresis showed DNA fragmentation of the cortices of hyperforin-treated
      animals exhibiting PPI deficit. CONCLUSIONS: The exacerbating effect of St.
      John's wort extract on PPI deficit may provide a limitation for using the extract
      to manage cognitive disturbance in psychotic and Huntington's disease patients
      manifesting PPI deficit.

PMID- 19171187
TI  - The mitochondrial theory of aging: insight from transgenic and knockout mouse
      models.
AB  - A substantial body of evidence has accumulated over the past 35 years in support
      of a role for oxidative damage to the mitochondrial respiratory chain and
      mitochondrial DNA in the determination of mammalian lifespan. The goal of this
      review is to provide a concise summary of recent studies using transgenic and
      knockout mouse models with altered expression of mitochondrial antioxidant
      enzymes (MnSOD (Sod2Tg and Sod2(+/-)), thioredoxin 2 (Trx2(+/-)), mitochondrial
      targeted catalase (mCAT) and mutant mice models that have been genetically
      manipulated to increase mitochondrial deletions or mutations
      (Polgamma(D257A/D257A) mutant mice) to examine the role of mitochondrial
      oxidative stress in aging. The majority of studies using these strategies do not
      support a clear role for mitochondrial oxidative stress or a vicious cycle of
      oxidative damage in the determination of lifespan in mice and furthermore do not
      support the free radical theory of aging. However, several key questions remain
      to be addressed and clearly more studies are required to fully understand the
      role of mitochondria in age-related disease and aging.

PMID- 19171189
TI  - WITHDRAWN: Fem1b interacts with Ankrd37 in mouse testis and induces its
      degradation by ubiquitin-mediated proteolysis pathway.
AB  - This article has been withdrawn at the request of the authors. The Publisher
      apologises for any inconvenience that this may cause. The full Elsevier Policy on
      Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 19171188
TI  - Chronic discrimination predicts higher circulating levels of E-selectin in a
      national sample: the MIDUS study.
AB  - Chronic discrimination in both minority and non-minority populations is linked to
      adverse health outcomes, including increased risk of cardiovascular disease and
      increased mortality, but the biological processes through which discrimination
      affects health are unclear. The current study tested the hypothesis that
      discrimination in a sample of Caucasians would predict elevated serum levels of E
      selectin, an indication of endothelial dysfunction which itself is associated
      with atherosclerosis and cardiovascular disease risk. Participants (N=804) in the
      biomarker sample from the Survey of Midlife in the United States (MIDUS) provided
      information about experiences of both major and everyday discrimination at two
      times separated by a 9-10 year interval. The discrimination measures were
      designed to assess perceived unfair treatment (e.g. being fired unfairly)
      independently of the perceived reasons for the unfair treatment (e.g. race,
      gender). Serum E-selectin was measured at the second wave of data collection.
      Women reported significantly more instances of major (P<0.05) and everyday
      P<0.001) discrimination than men. Analyses of Covariance (ANCOVA) showed that
      both greater lifetime exposure to major discrimination (P<0.05) and chronic
      exposure to everyday discrimination (P<0.05) predicted higher circulating levels
      of E-selectin, but only in men. These associations remained statistically
      significant after adjustments for potential confounding variables, including age,
      race, socioeconomic status, health status, and health behavior. These results
      highlight a potential biological mechanism by which exposure to unfair treatment
      may be related to health, particularly cardiovascular function. Moreover, they
      add to a growing literature suggesting that unfair treatment in general may
      predict adverse health outcomes.

PMID- 19171190
TI  - Calcium-calmodulin-dependent kinase II (CaMKII) mediates insulin-stimulated
      proliferation and glucose uptake.
AB  - Cellular growth and glucose uptake are regulated by multiple signals generated by
      the insulin receptor. The mechanisms of individual modulation of these signals
      remain somewhat elusive. We investigated the role of CaMKII in insulin signalling
      in a rat skeletal muscle cell line, demonstrating that CaMKII modulates the
      insulin action on DNA synthesis and the negative feedback that down regulates
      glucose uptake. Insulin stimulation generated partly independent signals leading
      to the rapid activation of Akt, Erk-1/2 and CaMKII. Akt activation was followed
      by Glut-4 translocation to the plasma membrane and increase of glucose uptake.
      Then, IRS-1 was phosphorylated at S612, the IRS-1/p85PI3K complex was disrupted,
      Akt was no more phosphorylated and both Glut-4 translocation and glucose uptake
      were reduced. Inhibition of CaMKII abrogated the insulin-induced Erk-1/2
      activation, DNA synthesis and phosphorylation of IRS-1 at S612. Inhibition of
      CaMKII also abrogated the down-regulation of insulin-stimulated Akt
      phosphorylation, Glut-4 membrane translocation and glucose uptake. These results
      demonstrate that: 1 - CaMKII modulates the insulin-induced Erk-1/2 activation and
      cell proliferation; 2 - after the initial stimulation of the IRS-1/Akt pathway,
      CaMKII mediates the down-regulation of stimulated glucose uptake. This represents
      a novel mechanism in the selective control of insulin signals, and a possible
      site for pharmacological intervention.

PMID- 19171191
TI  - Calcium and ATP handling in human NADH:ubiquinone oxidoreductase deficiency.
AB  - Proper cell functioning requires precise coordination between mitochondrial ATP
      production and local energy demand. Ionic calcium (Ca(2+)) plays a central role
      in this coupling because it activates mitochondrial oxidative phosphorylation
      (OXPHOS) during hormonal and electrical cell stimulation. To determine how
      mitochondrial dysfunction affects cytosolic and mitochondrial Ca(2+)/ATP
      handling, we performed life-cell quantification of these parameters in fibroblast
      cell lines derived from healthy subjects and patients with isolated deficiency of
      the first OXPHOS complex (CI). In resting patient cells, CI deficiency was
      associated with a normal mitochondrial ([ATP](m)) and cytosolic ([ATP](c)) ATP
      concentration, a normal cytosolic Ca(2+) concentration ([Ca(2+)](c)), but a
      reduced Ca(2+) content of the endoplasmic reticulum (ER). Furthermore, cellular
      NAD(P)H levels were increased, mitochondrial membrane potential was slightly
      depolarized, reactive oxygen species (ROS) levels were elevated and mitochondrial
      shape was altered. Upon stimulation with bradykinin (Bk), the peak increases in
      [Ca(2+)](c), mitochondrial Ca(2+) concentration ([Ca(2+)](m)), [ATP](c) and
      [ATP](m) were reduced in patient cells. In agreement with these results, ATP
      dependent Ca(2+) removal from the cytosol was slower. Here, we review the
      interconnection between cytosolic, endoplasmic reticular and mitochondrial Ca(2+)
      and ATP handling, and summarize our findings in patient fibroblasts in an
      integrative model.

PMID- 19171192
TI  - Vacuolar H+-ATPase meets glycosylation in patients with cutis laxa.
AB  - Glycosylation of proteins is one of the most important post-translational
      modifications. Defects in the glycan biosynthesis result in congenital
      malformation syndromes, also known as congenital disorders of glycosylation
      (CDG). Based on the iso-electric focusing patterns of plasma transferrin and
      apolipoprotein C-III a combined defect in N- and O-glycosylation was identified
      in patients with autosomal recessive cutis laxa type II (ARCL II). Disease
      causing mutations were identified in the ATP6V0A2 gene, encoding the a2 subunit
      of the vacuolar H(+)-ATPase (V-ATPase). The V-ATPases are multi-subunit, ATP
      dependent proton pumps located in membranes of cells and organels. In this
      article, we describe the structure, function and regulation of the V-ATPase and
      the phenotypes currently known to result from V-ATPase mutations. A clinical
      overview of cutis laxa syndromes is presented with a focus on ARCL II. Finally,
      the relationship between ATP6V0A2 mutations, the glycosylation defect and the
      ARCLII phenotype is discussed.

PMID- 19171193
TI  - A novel amino acid substitution in a voltage-gated sodium channel is associated
      with knockdown resistance to permethrin in Aedes aegypti.
AB  - To identify pertinent mutations associated with knockdown resistance to
      permethrin, the entire coding sequence of the voltage-gated sodium channel gene
      Aa-para was sequenced and analyzed from a Per-R strain with 190-fold resistance
      to permethrin and two susceptible strains of Aedes aegypti. The longest
      transcript, a 6441bp open reading frame, encodes 2147 amino acid residues with an
      estimated molecular mass of 241kDa. A total of 33 exons were found in the Aa-para
      gene over 293kb of genomic DNA. Three previously unreported optional exons were
      identified. The first two exons, m and n, were located within the intracellular
      domain I/II, and the third, f', was found within the II/III linkers. The two
      mutually exclusive exons, d and l, were the only alternative exons in all the
      cDNA clones sequenced in this study. The most distinct finding was a novel amino
      acid substitution mutation, D1794Y, located within the extracellular linker
      between IVS5 and IVS6, which is concurrent with the known V1023G mutation in Aa
      para of the Per-R strain. The high frequency and coexistence of the two mutations
      in the Per-R strain suggest that they might exert a synergistic effect to provide
      the knockdown resistance to permethrin. Furthermore, both cDNA and genomic DNA
      data from the same individual mosquitoes have demonstrated that RNA editing was
      not involved in amino acid substitutions of the Per-R strain.

PMID- 19171195
TI  - Supercalifragilisticexpialidocious: how the brain learns words never heard
      before.
AB  - Vocabulary acquisition is such a major aspect of language learning in children,
      but also in adults when learning a foreign language, that a dedicated vocabulary
      learning device may exist within the language organ. To identify the relevant
      brain systems, we performed regional cerebral blood flow measurements in normal
      subjects while they were learning a list of neologisms or a list of word-nonword
      pairs. Structures implicated in phonological short-term memory (Broca's area,
      left temporo-parietal junction) were steadily activated during nonwords learning,
      while the left temporal lobe neocortical and paralimbic structures
      (parahippocampal region), associated with long-term memory, contributed to
      learning in a time-dependent manner, with maximal activation at the beginning of
      the process. The neural system specifically activated when learning new
      vocabulary was strongly lateralized to the left hemisphere. This evidence refines
      current models of memory function and supports theories which emphasise the
      importance of phonological competence in hemispheric dominance for language.

PMID- 19171194
TI  - Truncated dystrophins can influence neuromuscular synapse structure.
AB  - Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and
      structural defects in the neuromuscular synapse that are caused by mutations in
      dystrophin. Whether aberrant neuromuscular synapse structure is an indirect
      consequence of muscle degeneration or a direct result of loss of dystrophin
      function is not known. Rational design of truncated dystrophins has enabled the
      design of expression cassettes highly effective at preventing muscle degeneration
      in mouse models of DMD using gene therapy. Here we examined the functional
      capacity of a minidystrophin (minidysGFP) and a microdystrophin
      (microdystrophin(DeltaR4-R23)) transgene on the maturation and maintenance of
      neuromuscular junctions (NMJ) in mdx mice. We found that minidysGFP prevents
      fragmentation and the loss of postsynaptic folds at the NMJ. In contrast,
      microdystrophin (DeltaR4-R23) was unable to prevent synapse fragmentation in the
      limb muscles despite preventing muscle degeneration, although fragmentation was
      observed to temporally correlate with the formation of ringed fibers.
      Surprisingly, microdystrophin(DeltaR4-R23) increased the length of synaptic folds
      in the diaphragm muscles of mdx mice independent of muscle degeneration or the
      formation of ringed fibers. We also demonstrate that the number and depth of
      synaptic folds influences the density of voltage-gated sodium channels at the
      neuromuscular synapse in mdx, microdystrophin(DeltaR4-R23)/mdx and mdx:utrophin
      double knockout mice. Together, these data suggest that maintenance of the
      neuromuscular synapse is governed through its lateral association with the muscle
      cytoskeleton, and that dystrophin has a direct role in promoting the maturation
      of synaptic folds to allow more sodium channels into the junction.

PMID- 19171196
TI  - Phylogenetic analysis of Fosterella L.B. Sm. (Pitcairnioideae, Bromeliaceae)
      based on four chloroplast DNA regions.
AB  - The about 31 species of Fosterella L.B. Sm. (Bromeliaceae) are terrestrial herbs
      with a centre of diversity in the central South American Andes. To resolve infra-
      and intergeneric relationships among Fosterella and their putative allies, we
      conducted a phylogenetic analysis based on sequence data from four chloroplast
      DNA regions (matK gene, rps16 intron, atpB-rbcL and psbB-psbH intergenic
      spacers). Sequences were generated for 96 accessions corresponding to 60 species
      from 18 genera. Among these, 57 accessions represented 22 of the 31 recognized
      Fosterella species and one undescribed morphospecies. Maximum parsimony and
      Bayesian inference methods yielded well-resolved phylogenies. The monophyly of
      Fosterella was strongly supported, as was its sister relationship with a clade
      comprising Deuterocohnia, Dyckia and Encholirium. Six distinct evolutionary
      lineages were distinguished within Fosterella. Character mapping indicated that
      parallel evolution of identical character states is common in the genus.
      Relationships between species and lineages are discussed in the context of
      morphological, ecological and biogeographical data as well as the results of a
      previous amplified fragment length polymorphism (AFLP) study.

PMID- 19171197
TI  - The ability of non-bacteriocin producing Streptococcus bovis strains to bind and
      transfer bovicin HC5 to other sensitive bacteria.
AB  - Streptococcus bovis HC5 produces a broad spectrum lantibiotic (bovicin HC5), but
      S. bovis JB1 does not have antimicrobial activity. Preliminary experiments
      revealed an anomaly. When S. bovis JB1 cells were washed in stationary phase S.
      bovis HC5 cell-free culture supernatant, the S. bovis JB1 cells were subsequently
      able to inhibit hyper-ammonia producing ruminal bacteria (Clostridium
      sticklandii, Clostridium aminophilum and Peptostreptococcus anaerobius). Other
      non-bacteriocin producing S. bovis strains also had the ability to bind and
      transfer semi-purified bovicin HC5. Bovicin HC5 that was bound to S. bovis JB1
      was much more resistant to Pronase E than cell-free bovicin HC5, but it could be
      inactivated if the incubation period was 24 h. Acidic NaCl treatment (100 mM, pH
      2.0) liberates half of the bovicin HC5 from S. bovis HC5, but it did not prevent
      bovicin HC5 from binding to S. bovis JB1. Acidic NaCl liberated some bovicin HC5
      from S. bovis JB1, but the decrease in activity was only 2-fold. Bovicin HC5 is a
      positively charged peptide, and the ability of S. bovis JB1 to bind bovicin HC5
      could be inhibited by either calcium or magnesium (100 mM). Acidic NaCl-treated
      S. bovis JB1 cells were unable to accumulate potassium, but they were still able
      to bind bovicin HC5 and prevent potassium accumulation by untreated S. bovis JB1
      cells. Based on these results, bovicin HC5 bound to S. bovis JB1 cells still acts
      as a pore-forming lantibiotic.

PMID- 19171198
TI  - Siderophore synthesis in Magnaporthe grisea is essential for vegetative growth,
      conidiation and resistance to oxidative stress.
AB  - The plant pathogenic fungus Magnaporthe grisea excretes siderophores of the
      coprogen-type for iron acquisition and uses ferricrocin for intracellular iron
      storage. In the present report we characterize mutants with defects in
      extracellular siderophore biosynthesis. Deletion of the M. grisea SSM2 gene,
      which encodes a non-ribosomal peptide synthetase, resulted in a loss of the
      production of all coprogens. The mutant strains had a reduced growth rate,
      produced fewer conidia and were more sensitive to oxidative stress. Ferricrocin
      production was not affected. Upon deletion of M. grisea OMO1, a gene predicted to
      encode an L-ornithine-N(5)-monooxygenase, no siderophores of any type were
      detected, the strain was aconidial, growth rate was reduced and sensitivity to
      oxidative stress was increased. Abundance of several proteins was affected in the
      mutants. The Deltassm2 and Deltaomo1 mutant phenotypes were complemented by
      supplementation of the medium with siderophores or reintroduction of the
      respective genes.

PMID- 19171199
TI  - Partial characterization of a malonyl-CoA-sensitive carnitine O
      palmitoyltransferase I from Macrobrachium borellii (Crustacea: Palaemonidae).
AB  - The shuttle system that mediates the transport of fatty acids across the
      mitochondrial membrane in invertebrates has received little attention. Carnitine
      O-palmitoyltransferase I (EC 2.3.1.21; CPT I) is a key component of this system
      that in vertebrates controls long-chain fatty acid beta-oxidation. To gain
      knowledge on the acyltransferases in aquatic arthropods, physical, kinetic,
      regulatory and immunological properties of CPT of the midgut gland mitochondria
      of Macrobrachium borellii were assayed. CPT I optimum conditions were 34 degrees
      C and pH=8.0. Kinetic analysis revealed a Km for carnitine of 2180+/-281 microM
      and a Km for palmitoyl-CoA of 98.9+/-8.9 microM, while V(max) were 56.5+/-6.6 and
      36.7+/-4.8 nmol min(-1) mg protein(-1), respectively. A Hill coefficient, n~1,
      indicate a Michaelis-Menten behavior. The CPT I activity was sensitive to
      regulation by malonyl-CoA, with an IC(50) of 25.2 microM. Electrophoretic and
      immunological analyses showed that a 66 kDa protein with an isoelectric point of
      5.1 cross-reacted with both rat liver and muscle-liver anti CPT I polyclonal
      antibodies, suggesting antigenic similarity with the rat enzymes. Although CPT I
      displayed kinetic differences with insect and vertebrates, prawn showed a high
      capacity for energy generation through beta-oxidation of long-chain fatty acids.

PMID- 19171200
TI  - The involvement of cytochrome p450 (CYP) 26 in the retinoic acid metabolism of
      human epidermal keratinocytes.
AB  - All-trans retinoic acid (RA) levels are controlled by enzymes of the vitamin A
      metabolism (RDH16, RalDH2, and LRAT) and RA catabolism (CYP26 and CYP2S1). Here,
      the mRNA expression of these enzymes was investigated in human keratinocytes at
      different Ca(2+)concentrations and after exposure to RA and CYP26 inhibitors.
      Cellular differentiation (high Ca(2+)) increased the expression of LRAT, RDH16
      and RalDH2, and decreased CYP26B1. RA (1 microM) induced CYP26A1, CYP26B1,
      CYP2S1, CRABPII and LRAT mRNA. The CYP26 inhibitor talarozole altered CYP26A1 and
      LRAT mRNA expression in a similar way as RA, increased the cellular accumulation
      of [(3)H]RA, and induced a punctate CRABPII staining, also observed after siRNA
      knock-down of CYP26B1 (but not after RA exposure). Furthermore, CYP26B1 siRNA
      increased the accumulation of [(3)H]RA and the CRABPII mRNA, suggesting an
      augmented retinoid signalling. Thus CYP26B1 appears essential for RA catabolism
      under physiological conditions, whereas CYP26A1 might play a greater role during
      RA excess.

PMID- 19171201
TI  - Towards role-based filtering of disease outbreak reports.
AB  - This paper explores the role of named entities (NEs) in the classification of
      disease outbreak report. In the annotation schema of BioCaster, a text mining
      system for public health protection, important concepts that reflect information
      about infectious diseases were conceptually analyzed with a formal ontological
      methodology and classified into types and roles. Types are specified as NE
      classes and roles are integrated into NEs as attributes such as a chemical and
      whether it is being used as a therapy for some infectious disease. We focus on
      the roles of NEs and explore different ways to extract, combine and use them as
      features in a text classifier. In addition, we investigate the combination of
      roles with semantic categories of disease-related nouns and verbs. Experimental
      results using naive Bayes and Support Vector Machine (SVM) algorithms show that:
      (1) roles in combination with NEs improve performance in text classification, (2)
      roles in combination with semantic categories of noun and verb features
      contribute substantially to the improvement of text classification. Both these
      results were statistically significant compared to the baseline "raw text"
      representation. We discuss in detail the effects of roles on each NE and on
      semantic categories of noun and verb features in terms of accuracy,
      precision/recall and F-score measures for the text classification task.

PMID- 19171202
TI  - Accuracy of simple biochemical tests in identifying liver fibrosis in patients co
      infected with human immunodeficiency virus and hepatitis C virus.
AB  - BACKGROUND & AIMS: We assessed the ability of 3 simple biochemical tests to stage
      liver fibrosis in patients co-infected with human immunodeficiency virus (HIV)
      and hepatitis C virus (HCV). METHODS: We analyzed liver biopsy samples from 324
      consecutive HIV/HCV-positive patients (72% men; mean age, 38 y; mean CD4+ T-cell
      counts, 548 cells/mm(3)). Scheuer fibrosis scores were as follows: 30% had F0,
      22% had F1, 19% had F2, 23% had F3, and 6% had F4. Logistic regression analyses
      were used to predict the probability of significant (>or=F2) or advanced (>or=F3)
      fibrosis, based on numeric scores from the APRI, FORNS, or FIB-4 tests (alone and
      in combination). Area under the receiver operating characteristic curves were
      analyzed to assess diagnostic performance. RESULTS: Area under the receiver
      operating characteristic curves analyses indicated that the 3 tests had similar
      abilities to identify F2 and F3; the ability of APRI, FORNS, and FIB-4 were as
      follows: F2 or greater: 0.72, 0.67, and 0.72, respectively; F3 or greater: 0.75,
      0.73, and 0.78, respectively. The accuracy of each test in predicting which
      samples were F3 or greater was significantly higher than for F2 or greater (APRI,
      FORNS, and FIB-4: >or=F3: 75%, 76%, and 76%, respectively; >or=F2: 66%, 62%, and
      68%, respectively). By using the lowest cut-off values for all 3 tests, F3 or
      greater was ruled out with sensitivity and negative predictive values of 79% to
      94% and 87% to 91%, respectively, and 47% to 70% accuracy. Advanced liver
      fibrosis (>or=F3) was identified using the highest cut-off value, with
      specificity and positive predictive values of 90% to 96% and 63% to 73%,
      respectively, and 75% to 77% accuracy. CONCLUSIONS: Simple biochemical tests
      accurately predicted liver fibrosis in more than half the HIV/HCV co-infected
      patients. The absence and presence of liver fibrosis are predicted fairly using
      the lowest and highest cut-off levels, respectively.

PMID- 19171203
TI  - Image of the month. Video imaging of acute bleeding from portal hypertensive
      gastropathy.

PMID- 19171206
TI  - Chymotryptic proteolysis accelerated by alternating current for MALDI-TOF-MS
      peptide mapping.
AB  - Alternating current (AC) has been employed to enhance the efficiency of
      chymotryptic proteolysis for peptide mapping. It was allowed to flow through the
      mixture solution of proteins and chymotrypsin via a pair of platinum wire
      electrodes. Bovine serum albumin (BSA) and cytochrome c (Cyt-c) were digested by
      the novel proteolysis approach to demonstrate its feasibility and performance.
      The results indicated that AC significantly accelerated in-solution chymotryptic
      proteolysis and the digestion time was substantially reduced to 5 min. The
      digests were identified by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS) with sequence coverages of 46% (BSA) and
      90% (Cyt-c) that were much better than those obtained by using 12-h conventional
      in-solution chymotryptic proteolysis. In addition, AC-assisted chymotryptic
      proteolysis was employed to digest human serum to demonstrate its suitability to
      complex protein sample. The present proteolysis strategy is simple and efficient
      and will find a wide range of applications in proteomic research.

PMID- 19171204
TI  - Physical Activity and Lymphedema (the PAL trial): assessing the safety of
      progressive strength training in breast cancer survivors.
AB  - Lymphedema is a chronic and progressive long-term adverse effect of breast cancer
      treatment commonly defined by swelling of the affected arm. Current clinical
      guidelines indicate that women with and at risk for lymphedema should protect the
      affected arm from overuse. In clinical practice, this often translates into risk
      aversive guidance to avoid using the arm. This could lead to a disuse pattern
      that may increase the likelihood of injury from common activities of daily
      living. Further, such guidance poses an additional barrier to staying physically
      active, potentially translating to weight gain, which has been shown to be
      associated with worse clinical course for women with lymphedema. We hypothesize
      that a program of slowly progressive strength training with no upper limit on the
      amount of weight that may be lifted would gradually increase the physiologic
      capacity of the arm so that common activities represent a decreasing percentage
      of maximal capacity. Theoretically, this increased capacity should decrease the
      risk that daily activities put stress on the lymphatic system of the affected
      side. The Physical Activity and Lymphedema (PAL) Trial is a recently completed
      randomized controlled exercise intervention trial that recruited 295 breast
      cancer survivors (141 with lymphedema at study entry, 154 at risk for lymphedema
      at study entry). The purpose of this report is to provide detail regarding the
      study design, statistical design, and protocol of the PAL trial.

PMID- 19171205
TI  - The immunology of atherothrombosis in the antiphospholipid syndrome: antigen
      presentation and lipid intracellular accumulation.
AB  - The antiphospholipid syndrome (APS), characterized by elevated serum levels of
      antiphospholipid antibodies (aPL) and thromboembolic complications, is a common
      cause of acquired hypercoagulability. The plasma protein beta2-glycoprotein I
      (beta2GPI) is the most clinically relevant antigenic target for aPL. Recent
      experimental evidence from our laboratory substantiated the concept that IgG anti
      beta2GPI immune complexes containing oxidized LDL (oxLDL) not only facilitated
      the intracellular accumulation of oxLDL in macrophages but also allowed the
      presentation of beta2GPI epitopes to pathogenic autoreactive T cells. Both
      mechanisms required FcgammaRI-mediated uptake by macrophages/monocytes.
      Furthermore, several clinical studies demonstrated that the presence of
      circulating oxLDL/beta2GPI complexes and IgG autoantibodies to these complexes
      was significantly associated with vascular inflammation (i.e. autoimmune-mediated
      atherothrombosis) in autoimmune patients. In this article, we review recent
      findings concerning the biochemical and immunologic mechanisms involved in
      autoimmune-mediated atherothrombosis in patients with APS.

PMID- 19171207
TI  - The management of paroxysmal nocturnal hemoglobinuria: recent advances in
      diagnosis and treatment and new hope for patients.

PMID- 19171208
TI  - Diabetic macular edema: pathogenesis and treatment.
AB  - Diabetic macular edema is a major cause of visual impairment. The pathogenesis of
      macular edema appears to be multifactorial. Laser photocoagulation is the
      standard of care for macular edema. However, there are cases that are not
      responsive to laser therapy. Several therapeutic options have been proposed for
      the treatment of this condition. In this review we discuss several factors and
      mechanisms implicated in the etiology of macular edema (vasoactive factors,
      biochemical pathways, anatomical abnormalities). It seems that combined
      pharmacologic and surgical therapy may be the best approach for the management of
      macular edema in diabetic patients.

PMID- 19171209
TI  - Literature review and meta-analysis of topical carbonic anhydrase inhibitors and
      ocular blood flow.
AB  - The purpose of this literature review and meta-analysis was to determine what, if
      any, effects topical carbonic anhydrase inhibitors have on ocular hemodynamics in
      humans. A literature review and meta-analysis was conducted to investigate the
      effects of topical carbonic anhydrase inhibitors on ocular blood flow. Thirty
      five articles were evaluated according to the inclusion criteria with 13
      manuscripts meeting requirements for statistical analysis. Each study's effect
      size, defined as the change in blood flow measures after treatment with topical
      carbonic anhydrase inhibitors, was estimated using the weighted mean difference.
      Based on this meta-analysis, we conclude that topical carbonic anhydrase
      inhibitors increase ocular blood flow velocities in the retinal circulation,
      central retinal and short posterior ciliary arteries, but not in the ophthalmic
      artery.

PMID- 19171210
TI  - Eye cancer related glaucoma: current concepts.
AB  - Eye cancer-related glaucomas occur through a variety of mechanisms. They can be
      challenging to diagnose and are often refractory to treatment. The literature
      reveals the variety of ways eye cancers cause glaucoma. Mechanisms include direct
      invasion, infiltration, or seeding of the aqueous outflow structures as well as
      indirect processes, such as compressive angle closure and anterior segment
      neovascularization. This review describes established, evolving, and new
      diagnostic techniques (e.g., high-frequency ultrasound and aspiration biopsy
      techniques). Treatment options typically depend upon the tumor type (primary or
      secondary), its location, and mechanism of glaucoma. However, they include
      standard pharmacologic, laser, incisional, and radiotherapeutic approaches. We
      hope this review leads to early detection and optimum treatment of eye cancer
      related glaucomas. Clearly, prompt diagnosis and management of eye cancer-related
      glaucoma offers an opportunity to both preserve vision and the patient's life.

PMID- 19171211
TI  - Retinal vascular caliber: systemic, environmental, and genetic associations.
AB  - Quantitative studies of retinal vascular caliber using new computer-assisted
      retinal imaging systems have allowed physicians and researchers to understand the
      influence of systemic, environmental, and genetic factors on retinal vascular
      caliber. Retinal vascular caliber changes reflect cumulative response to aging,
      cardiovascular risk factors, inflammation, nitric oxide-dependent endothelial
      dysfunction, and other processes. Recent epidemiological studies have shown that
      changes in retinal arteriolar and venular caliber size may reflect the
      differential effects of a range of systemic, environmental, and genetic risk
      factors. Narrower retinal arteriolar caliber and smaller arteriovenous ratio are
      associated with older age; higher levels of past, current, and future blood
      pressure and obesity; and predict the incidence of diabetes and coronary heart
      disease. Wider retinal venular caliber, in contrast, is associated with younger
      age; impaired fasting glucose and diabetes; dyslipidemia; obesity; systemic
      marker of inflammation, endothelial dysfunction, and cigarette smoking; and
      predicts the risk of stroke and coronary heart disease. New data from family and
      twin studies indicate a significant genetic contribution to retinal vascular
      caliber, an area that is under investigation. Elucidating the complete range of
      systemic, environmental, and genetic factors linked with retinal vascular caliber
      changes may provide critical insight into the etiology, pathogenesis, and natural
      history of early vascular disease not only in the eye but elsewhere in the body.

PMID- 19171212
TI  - Fundus autofluorescence and progression of age-related macular degeneration.
AB  - Fundus autofluorescence imaging is an imaging method that provides additional
      information compared to conventional imaging techniques. It permits to
      topographically map lipofuscin distribution of the retinal pigment epithelial
      cell monolayer. Excessive accumulation of lipofuscin granules in the lysosomal
      compartment of retinal pigment epithelium cells represents a common downstream
      pathogenetic pathway in various hereditary and complex retinal diseases including
      age-related macular degeneration (AMD). This comprehensive review contains an
      introduction in fundus autofluorescence imaging, including basic considerations,
      the origin of the signal, different imaging methods, and a brief overview of
      fundus autofluorescence findings in normal subjects. Furthermore, it summarizes
      cross-sectional and longitudinal fundus autofluorescence findings in patients
      with AMD, addresses the pathophysiological significance of increased fundus
      autofluorescence, and characterizes different fundus autofluorescence phenotypes
      as well as fundus autofluorescence alterations with disease progression.

PMID- 19171213
TI  - Iris varix: report of a case and review of iris vascular anomalies.
AB  - Iris vascular anomalies are rare benign vascular tumors and simulating lesions of
      the iris stroma. These can be classified into five distinct, clinicopathological
      entities: iris capillary hemangioma, iris cavernous hemangioma, iris
      microhemangioma, iris arteriovenous malformation, and iris varix. We have
      reviewed all reported cases of iris hemangiomas since 1970, as prior cases have
      been extensively reviewed by Ferry. We also report a case of an iris varix,
      confirmed by histopathological and immunohistochemical examination. Comparative
      features of each subtype of vascular anomaly are discussed.

PMID- 19171214
TI  - Sherlock Holmes in the ER (the case of red and the head).
AB  - A 58-year-old woman presented with a problem with her peripheral vision. Computed
      tomography scan showed an occipital hemorrhagic stroke. She subsequently suffered
      gastrointestinal bleeding and at surgery biopsy of a portion of the middle colic
      artery aneurysm revealed changes consistent with polyarteritis nodosa.

PMID- 19171215
TI  - Should Indocyanine green should be used to facilitate removal of the internal
      limiting membrane in macular hole surgery.
AB  - Indocyanine green (ICG) is one of several vital dyes that are used in
      vitreoretinal surgery to aid visualization of diaphanous collagenous tissues in
      what has been called chromovitrectomy. As shown herein, much has been written
      about the use and rather narrow safety profile of ICG. The discussion surrounding
      its applications would have ended long ago were it not for the occasional patient
      who keeps returning to the office with permanent central scotomas after ICG
      assisted macular hole surgery. The purpose of this Viewpoint is to reemphasize
      potential methods of proper use and clarify safety issues of this particular
      vital dye that enhances surgical technique but not necessarily visual outcome.

PMID- 19171217
TI  - Biography of louis braille and invention of the braille alphabet.
AB  - Louis Braille (1809-1852) was born in France. At the age of three, he wounded his
      right eye with a cobbler's tool while playing in his father's workshop. No
      medical knowledge could save his eyesight at that time. Louis's left eye became
      inflamed, apparently due to subsequent sympathetic ophthalmia, and he eventually
      lost the sight in that eye. At the age of five, Louis Braille was completely
      blind. He is considered to be the inventor of a writing system by touch that
      bears his name, the Braille system. This revolutionary system has allowed blind
      people to access written culture, and it can therefore be considered a major
      advance in the quality of life for the blind. The immediate precursor of the
      invention of the Braille system was the alphabet created by Charles Barbier de la
      Serre (1767-1841) who created a language by touch designed for military and
      secret use. Louis Braille modified this alphabet into the Braille alphabet, which
      is practically the same one that is currently used. It required time to be
      recognized and to be implemented as a reading and writing method for blind people
      throughout the world. In 1950, UNESCO effectively universalized the Braille
      alphabet, and in 2005 it recognized Braille system as a "vital language of
      communication, as legitimate as all other languages in the world."

PMID- 19171218
TI  - Toward more effective risk prevention.
AB  - Reviews of medical malpractice claims against ophthalmologists have revealed a
      pattern of misunderstanding and improper or underutilization of several risk
      prevention and defense techniques. This often results in increasing the risk of
      litigation and weakening the defense of the claims. These techniques include the
      physician-attorney relationship, dealing with differences in the patient's
      version of the facts versus that of the physician (he said-she said), the
      physician-patient relationship, informed refusal, awareness of whom we are trying
      to convince with our arguments, vicarious liability, subpoena duces tecum, the
      most dangerous diagnosis, and the management of unethical plaintiff witnesses.
      Many of these techniques have been extensively described in the literature. This
      article discusses the means by which to make optimal use of them in order to
      achieve maximal risk prevention and the strongest possible defense in the event
      of litigation.

PMID- 19171219
TI  - Recent trends in the management of rhegmatogenous retinal detachment.

PMID- 19171221
TI  - [The Annales de Dermatologie et de Venereologie is in good health].

PMID- 19171222
TI  - [Cosmetics and health. New frontiers, new confusion].

PMID- 19171223
TI  - [Cutaneous anthrax: seven cases].
AB  - BACKGROUND: Anthrax is an acute infection caused by the Gram-positive organism,
      Bacillus anthracis, which rarely affects humans under normal conditions.
      Depending on the mode of contamination, there are three distinct clinical forms:
      pulmonary, gastrointestinal and cutaneous. This type of infection is still common
      in the developing countries, a fact that should be borne in mind by examining
      doctors, and in particular by dermatologists. It is important to recognise the
      clinical aspects of this disease rarely encountered in clinical practice since
      any delay in treatment may have fatal consequences, as illustrated by our case
      reports. CASE REPORTS: Five men and two women of mean age 35years presented one
      or more cutaneous lesions of the upper limbs in all instances. All patients had a
      fever of 39-40 degrees C but none were presenting gastrointestinal or pulmonary
      signs. Neurological signs and/or disturbed consciousness were seen in three
      patients. Bacteriological diagnosis was based on isolation of B. anthracis in
      cultures of skin specimens. Treatment with parenteral or oral ciprofloxacin was
      initiated in six patients, and this therapy was combined with oral
      corticosteroids in three patients. A favourable outcome was achieved in four
      patients, while the remaining three patients died of their disease. DISCUSSION:
      Anthrax is an anthropozoonosis that has now become rare in the developed
      countries. The disease is contracted by humans through touching either animals
      killed by anthrax or the products thereof. The cases we report were subsequent to
      collective contamination of several members of a single family, probably due to
      contact with goats carrying the disease. If left untreated, cutaneous anthrax may
      progress in 5 to 20% of cases to septicaemia with potentially lethal central
      nervous system involvement. The only means of eradicating anthrax in animals, and
      thus in humans, is through animal vaccination.

PMID- 19171224
TI  - [Safety of reintroducing platelet-inhibitory doses of aspirin in patients with
      urticaria or angioedema induced by anti-inflammatory doses].
AB  - BACKGROUND: Aspirin is one of the most widely prescribed drugs in the world on
      account of its analgesic, antipyretic, and anti-inflammatory properties. Its
      effect on platelet aggregation makes it the first choice for prophylaxis in
      cardiovascular, neurological and obstetric diseases. However, a history of
      aspirin-induced urticaria and/or angioedema is usually a contraindication for
      further prescription of the drug. The aim of this article was to demonstrate that
      patients presenting aspirin-induced cutaneous reactions at anti-inflammatory
      doses can safely benefit from aspirin reintroduction at platelet-inhibitory
      doses. PATIENTS AND METHODS: Patients with a history of aspirin-induced urticaria
      and/or angioedema referred to our department between January 2000 and June 2008
      for double-blind placebo-controlled reintroduction at platelet-inhibitory doses
      for a medical indication were enrolled in this study. RESULTS: Seventy patients
      with aspirin hypersensitivity as well as a medical indication for this therapy
      were referred to our department. Of these, 38 (54.3%) had a history of aspirin
      induced urticaria and/or angioedema, including three laryngeal oedemas (7.9%).
      All subjects received platelet-inhibitory doses of aspirin (maximal total dose:
      400mg/day) in double-blind placebo-controlled fashion during a one-day
      hospitalization period. None of the patients presented an immediate
      hypersensitivity reaction. Only one patient, who had received a cumulative dose
      of 200mg/day, reported diffuse urticaria and facial angioedema of no clinical
      significance the following day. He had a history of chronic urticaria.
      CONCLUSION: This article demonstrates the safety of reintroducing platelet
      inhibitory doses of aspirin in patients in whom it is indicated and reporting
      aspirin-induced urticaria and/or angioedema with anti-inflammatory doses.
      However, patients with a history of chronic urticaria should undergo a challenge
      with the lowest platelet-inhibitory dose (75mg/day) in order to minimize the risk
      of aggravating their condition.

PMID- 19171225
TI  - [Publication rate for oral presentations made at the Journees Dermatologiques de
      Paris meeting].
AB  - BACKGROUND: The fate of oral presentations presented at a dermatological meeting
      has not been assessed to date. Our aim was to determine the publication rate for
      oral presentations presented at the "Journees dermatologiques de Paris" (JDP)
      meeting in peer-reviewed journals. Our secondary goals were to identify factors
      associated with publication and to examine the consistency of reporting of
      research findings presented in the conference abstract and subsequent full
      publication. METHODS: Abstracts presented orally at the JDP 1999-2004 were
      identified in the book of congress abstracts. Two independent operatives
      performed a Medline search cross-referencing lead and last authors and keywords.
      RESULTS: The publication rate was 57.6% with mean time to publication of
      20.3months. The median impact factor was 2.8. Factors associated with subsequent
      publication were study topic (p=0.04 for oncology) and study type (p=0.03 for
      fundamental research and p=0.005 for randomized controlled trials). The congress
      abstracts and full-text publication differed primarily in terms of sample size
      and data given in the "Results" section. DISCUSSION: More than half of all
      abstracts presented orally at the JDP congress are subsequently published in
      journals with a median impact factor comparable to those seen for other
      scientific congresses for which similar analysis has been conducted. These
      results confirm the scientific quality of this particular congress, in addition
      to its vocation of continuous medical training.

PMID- 19171226
TI  - [Anhidrotic ectodermal dysplasia. Report of a rare mutation in EDA1].
AB  - BACKGROUND: Anhidrotic ectodermal dysplasia is a rare inherited disorder seen
      mainly in the X-linked recessive form. We report the case of a Lebanese family in
      which the mother transmitted an uncommon missense mutation to three of her sons.
      PATIENTS AND METHODS: A 23-year-old patient presented with keloids in nodular
      acne. The physical examination showed fine and sparse hair, thick everted lips
      and dental defects. A detailed history revealed congenital anhidrosis. The
      patient's, seven-year-old and four-year-old brothers had the same characteristic
      facial morphology and were also presenting anhidrosis. The mother had hypodontia.
      The parents, though not consanguineous, were from the same village. Genetic
      testing with sequencing of the EDA1 gene revealed a missense mutation affecting
      codon 155. DISCUSSION: Ectodermal dysplasias are currently found in more than 150
      syndromes. The patient's history and the clinical signs suggest the X-linked
      recessive form of anhidrotic ectodermal dysplasia due to a mutation in EDA1 gene
      encoding the ectodysplasin. The mutation found in this family is very rare and
      was mentioned once in a study on splicing forms that permit detection of all EDA1
      mutations. Besides, this patient tolerated oral isotretinoin perfectly well,
      unlike another case reported once in the literature. Finally, genetic counselors
      must inform carrier mothers of the high recurrence rate among male offspring.

PMID- 19171227
TI  - [Acral circumscribed hypokeratosis of plantar and dorsum of the finger
      localization: two cases].
AB  - INTRODUCTION: Palmar or plantar circumscribed hypokeratosis is a remarkable
      clinicopathologic entity described in 2002. It consists in a well demarcated
      decrease in thickness of the stratum corneum, that can be clinically mistaken for
      Bowen's disease or porokeratosis. We present a classical plantar localisation and
      a more original case on the dorsum of the finger, together with a microscopic and
      immunohistochemical study. CASE REPORTS: Case 1. A 65-year-old man was seen 15
      years after a first consultation for a well demarcated 1.5cm erythematous lesion
      localised on the border of his left foot. The biopsy, then misinterepreted as
      keratosis sulcata, was reviewed. It showed a sudden and well demarcated decrease
      in thickness of the stratum corneum, overlying a slightly acanthotic epidermis,
      associated with dilated capillaries in the papillary dermis. HPV immunostaining
      was negative. Case 2. A 75-year-old woman had a well demarcaated erythematous
      lesion of the dorsum of her right index finger, lasting for months without
      significant evolution. A first biopsy showed pale and haloed keratinocytes that
      could be interpreted as koilocytes. She was therefore treated by cryotherapy, 5
      fluro-uracile and imiquimod, that proved unsuccessful. A second biopsy showed a
      sudden and major decrease in thickness of the stratum corneum, overlying an area
      containing a few pale keratinocytes with perinuclear halo. HPV immunostaing was
      negative and Ki67 positive cells were slightly decreased in number when compared
      to lateral normal skin. DISCUSSION: Our first case is typical of plantar
      hypokeratosis characterised by its long evolution, typical semiology and well
      demarcated anomaly of the stratum corneum. Our second case is original as it
      shows that the disease can also affect the dorsum of the fingers. Acral
      circumscribed hypokeratosis is therefore a better name for this condition. We did
      not find any arguments in favor of a viral cause or an increased proliferation of
      keratinocytes. As often described in other cases, the lesion can remain unchanged
      for decades, which confirm its benign evolution. Topical treatments are generally
      ineffective. The pathogenesis of this localised hypokeratosis remains mysterious.

PMID- 19171228
TI  - [Streptococcal perianal dermatitis and guttate psoriasis].
AB  - BACKGROUND: The link between guttate psoriasis and streptococcal infection is
      acknowledged. This form of psoriasis generally follows pharyngitis, but a small
      number of cases have been described as being triggered by a streptococcal
      infection other than in the throat. We report the case of a child with
      streptococcal anitis followed by guttate psoriasis. CASE REPORT: A 4-year-old boy
      presented painful perianal erythema present for two weeks with diffuse lesions of
      guttate psoriasis present since the second week. Group A beta-haemolytic
      streptococcus was found during bacterial examination of the anal region. After
      one month of antibiotic treatment with josamycin combined with daily application
      of desonide 0.05% topical cream, all symptoms subsided without relapse in the
      ensuing 6 months. DISCUSSION: This case demonstrates the need for careful
      clinical examination, both of the nose and throat but also of the perianal
      region, in children consulting for guttate psoriasis. It also demonstrates the
      strong link between guttate psoriasis and streptococcal infections in certain
      patients.

PMID- 19171229
TI  - [Orange skin and xanthomas associated with lycopenaemia in a setting of type III
      dyslipoproteinemia].
AB  - BACKGROUND: Type III hyperlipoproteinaemia (HLP) is a rare form of dyslipidaemia
      characterized by skin lesions such as palmar crease xanthoma and tuberous
      xanthomas. To our knowledge, there have been no previous reports of yellow-orange
      discoloration of the skin and xanthomas associated with this disease. CASE
      REPORT: A 61-year-old woman consulted for palmar crease xanthoma and tuberous
      xanthomas of the elbows with odd yellow-orange discoloration. Laboratory
      investigations demonstrated type-III HLP and a high serum lycopene level. After
      14 weeks of lipid-lowering treatment, the xanthomas and discoloration showed
      improvement. In addition, lipid levels and serum lycopene had returned to normal.
      DISCUSSION: All cases of lycopenaemia reported in the literature followed
      excessive ingestion of lycopene in foods. We describe the first case of
      lycopenaemia with orange discoloration of xanthomas following raised serum
      lycopene but not involving excessive dietary intake. Type-III HLP was doubtless
      instrumental in the physiopathogenesis of these orange lesions.

PMID- 19171230
TI  - [Pyoderma gangrenosum with aseptic spleen abscess].
AB  - BACKGROUND: Pyoderma gangrenosum is a neutrophilic dermatosis in which systemic
      involvement is rare. It may be associated with systemic disease. We report a case
      of pyoderma gangrenosum in the spleen. CASE REPORT: A 68-year-old man presenting
      pyoderma gangrenosum with pustules and stage I multiple myeloma was admitted for
      asthenia and abdominal pain. There were no skin lesions. Laboratory tests showed
      inflammatory syndrome with polynuclear leucocytes of 25,000/mm(3). CAT scans and
      abdominal ultrasound revealed a splenic abscess. A spleen biopsy was performed
      and histological examination showed polynuclear leukocyte infiltration, while
      cultures were negatives. Diagnosis of pyoderma gangrenosum with splenic
      involvement was made. Increased systemic corticosteroid therapy produced a
      successful outcome. Haematological findings remained unchanged. DISCUSSION:
      Spleen involvement in pyoderma gangrenosum is very rare and can mimic an
      infectious process. In such cases, routine screening is essential for associated
      diseases, particularly haematological malignancies.

PMID- 19171232
TI  - [Guidelines for the good use of isotretinoin in private practice: a prospective
      observational study of 1263 acne patients].

PMID- 19171231
TI  - [Atorvastatin-induced drug reaction with eosinophilia and systemic symptoms
      (DRESS)].
AB  - BACKGROUND: Atorvastatin is a widely-used therapeutic statin given for
      hypercholesterolaemia and for prevention of cardiovascular events. We report
      herein the occurrence of a drug reaction with eosinophilia and systemic symptoms
      (DRESS) secondary to intake of this drug. CASE REPORT: A 58-year-old woman
      presented with a febrile skin rash and facial oedema, appearing 6weeks after the
      start of atorvastatin for dyslipidaemia. The clinical features associated
      disseminated polymorphic lesions, oral mucosa involvement and systemic symptoms
      (fever, abdominal pain, diarrhoea, polyarthralgia and adenomegaly). Blood tests
      showed hypereosinophilia up to 11,540/mm(3), inflammatory syndrome and anicteric
      cholestasis without cytolysis. Serological tests for hepatitis B and C, HIV, EBV,
      HHV-6, HHV-8, CMV and human Parvovirus B-19 were negative. Cutaneous histology
      was unspecific. A diagnosis of DRESS secondary to atorvastatin was suspected. The
      clinical outcome was favourable after atorvastatin discontinuation. DISCUSSION:
      To our knowledge, this is the first description of atorvastatin inducing DRESS, a
      severe life-threatening drug eruption. Atorvastatin has previously been
      implicated in various cutaneous adverse events. Because of their potentially
      serious side effects, prescription of statins must be carefully evaluated.

PMID- 19171233
TI  - [Sweet syndrome induced by chloroquine].

PMID- 19171234
TI  - [New nonsense mutation (p.E250X) in the tyrosinase gene of a patient with
      oculocutaneous albinism type 1A].

PMID- 19171235
TI  - [Acute dermohypodermitis of the right leg (S. putrefaciens) after sea bathing].

PMID- 19171236
TI  - [Melanoma during latanoprost therapy: three cases].

PMID- 19171238
TI  - [A nodule of the scalp].

PMID- 19171237
TI  - [Persistent painful periorificial ulcerations].

PMID- 19171239
TI  - [Juvenile xanthogranuloma].

PMID- 19171240
TI  - [Severe photosensitivity reactions].

PMID- 19171241
TI  - [Contact allergy to fragrance mix].

PMID- 19171242
TI  - [Hypercholesterolemic xanthomas in an 8-year-old boy].

PMID- 19171243
TI  - [Congenital macroglossia (Wiedmann-Beckwith syndrome)].

PMID- 19171244
TI  - [The Annales de Dermatologie in 1908 - dermatitis in the newborn infant
      (infantile erythema): a histological study].

PMID- 19171245
TI  - [Intravenous fluorescein and Raynaud's phenomenon].

PMID- 19171246
TI  - Infection control practices related to Clostridium difficile infection in acute
      care hospitals in Canada.
AB  - BACKGROUND: We carried out a survey to identify the infection prevention and
      control practices in place in Canadian hospitals participating in the Canadian
      Nosocomial Infection Surveillance Program (CNISP). METHODS: An infection
      prevention and control practices survey was sent to CNISP hospitals at the
      beginning of November 2004, the same time that CNISP started a 6-month
      prospective surveillance for Clostridium difficile infection (CDI) to evaluate
      their infection prevention and control measures and laboratory methods for C
      difficile. RESULTS: A total of 33 hospitals completed and returned the survey.
      Infection control precautions were initiated in 18 hospitals (55%) due to the
      presence of a symptomatic patient before the C difficile laboratory tests were
      available. All of the hospitals used gloves and gowns as additional precautions.
      Twenty-three hospitals (70%) tested liquid stools based on a clinician's order,
      and 8 (24%) tested all liquid stools submitted whether of not C difficile testing
      was requested. The hospitals used 1 of 3 different products as a standard
      hospital-wide disinfectant; 24 (73%) used a quaternary ammonium compound, 8 (24%)
      used accelerated hydrogen peroxide, and 1 (3%) used a hypochlorite solution (1:10
      bleach solution). CONCLUSION: Although the hospitals used contact precautions
      quite uniformly, considerable variation was seen among hospitals in terms of
      testing strategies, cleaning and disinfection protocols and products, and
      isolation practices. The timing for the initiation of infection control
      precautions is important to prevent secondary transmission of CDI. Most of the
      hospitals implemented precautions while waiting for the toxin assay results.

PMID- 19171247
TI  - What is on that keyboard? Detecting hidden environmental reservoirs of
      Clostridium difficile during an outbreak associated with North American pulsed
      field gel electrophoresis type 1 strains.
AB  - BACKGROUND: Numerous studies have demonstrated that environmental surfaces in the
      rooms of patients with Clostridium difficile infection (CDI) are often
      contaminated with spores. However, less information is available regarding the
      frequency of contamination of environmental surfaces outside of CDI isolation
      rooms. METHODS: We performed a point-prevalence culture survey for C difficile in
      rooms of patients not in isolation for CDI, in physician and nurse work areas,
      and on portable equipment, including pulse oximetry devices, electrocardiogram
      machines, mobile computers, and medication distribution carts. Isolates were
      characterized by assessment of toxin production, polymerase chain reaction (PCR)
      ribotyping, and PCR for binary toxin genes. RESULTS: Of 105 nonisolation rooms,
      17 (16%) were contaminated with toxin-producing C difficile, with the highest
      rate of contamination on the spinal cord injury unit (32%). Of 87 surfaces
      cultured outside of patient rooms, 20 (23%) were contaminated, including 9 of 29
      (31%) in physician work areas, 1 of 10 (10%) in nurse work areas, and 9 of 43
      (21%) portable pieces of equipment, including a pulse oximetry finger probe,
      medication carts, and bar code scanners on medication carts. Of 26 isolates
      subjected to typing, 19 (73%) matched ribotype patterns detected in stool samples
      from CDI patients and 13 (50%) were epidemic, binary toxin-positive strains.
      CONCLUSION: In the context of a CDI outbreak, we found that environmental
      contamination was common in nonisolation rooms, in physician and nurse work
      areas, and on portable equipment. Further research is needed to determine whether
      contamination in these areas plays a significant role in transmission.

PMID- 19171248
TI  - Risk factors for increased mortality from hospital-acquired versus community
      acquired infections in febrile medical patients.
AB  - BACKGROUND: Risk factors for hospital-acquired infection and attributable
      mortality in surgical and critically ill patients are well-known. We sought to
      identify factors associated with increased mortality from hospital-acquired
      infections as compared with community-acquired infections in patients with new
      onset fever and a presumed infectious focus (n = 212), in a department of
      internal medicine. METHODS: Demographic, clinical, and laboratory variables were
      studied for 2 days after inclusion. Septic shock and outcome were monitored for
      up to 7 and 28 days after inclusion, respectively. RESULTS: Of the 212 patients,
      54 had hospital-acquired and 158 community-acquired infection, with septic shock
      rates of 15% and 4% and mortality rates of 24% and 6% (P = .001), respectively.
      Prior neurologic disease was associated with death. Patients with hospital
      acquired infection had more often (intravascular) devices and underwent more
      often interventions, had a different distribution of infectious foci, and had
      more often bacteremia. Bacteremia-associated septic shock was associated with
      nonsurvival in both infection groups. The causative agents were not associated
      with outcome, and the clinical and laboratory host response associated with
      nonsurvival generally did not differ among infection groups. CONCLUSION: Our data
      suggest that hospital-acquired infections carry a higher crude mortality rate
      than community-acquired infection in febrile medical patients, mainly because of
      more frequent use of devices and hospital interventions and resultant bacteremia
      and septic shock, rather than by differences in underlying diseases, causative
      agents, and clinical and laboratory host responses. The observations thus
      emphasize the continued importance of preventive measures on medical wards of our
      hospital and can be used for comparison with future studies.

PMID- 19171249
TI  - Bacterial counts from hospital doctors' ties are higher than those from shirts.
AB  - Doctor ties are often contaminated with bacteria, and it has been suggested that
      they should not be worn. We have compared bacterial counts from the ties and
      shirt pockets of 50 doctors. Counts were higher (P = .002) from ties that were
      rarely, if ever, cleaned than from shirts that were washed every 2 days or more
      frequently. The results support the need for further research on unwashable
      clothing of hospital staff.

PMID- 19171250
TI  - Infection control in developing countries: Phnom Penh and Kabul.

PMID- 19171251
TI  - Temporal variation in the incidence of catheter-associated urinary tract
      infection at a Thai tertiary care center.

PMID- 19171252
TI  - The survivability of Bacillus anthracis (Sterne strain) in processed liquid eggs.
AB  - In this study, we investigated the survival and inactivation kinetics of a
      surrogate strain of Bacillus anthracis (Sterne strain) in whole egg (WE), egg
      white (EW), sugared egg yolk (YSU), and salted egg yolk (YSA) at low (-20, 0, and
      5 degrees C), moderate (15, 20, 25, 30, 35, and 40 degrees C), and high storage
      temperatures (45, 50, 55, and 60 degrees C). Outgrowth of the spores was measured
      as lag phase duration (LPD). Replication of vegetative cells was measured in
      terms of growth rate (GR) and maximum population density (MPD). Spore
      inactivation was recorded as inactivation rate and percent reduction in viable
      count. In general, spore viability decreased at low and high temperatures and
      increased at moderate temperatures. At 0 and 5 degrees C, a 60-100% reduction in
      spore viability was seen within 2-3 weeks in WE and YSU, 0-30% in YSA, and 50
      100% in EW. At -20 degrees C, however, no drop in spore titer was observed in YSU
      and EW but a 20% drop in titer was seen in YSA and 50% in WE within 2-3 weeks. At
      high temperatures, WE, EW, and YSA produced a 20-50% drop in the spore titer
      within 1-4h whereas YSU showed 100% inactivation within 0.75 h. At moderate
      storage temperatures, as the temperature increased from 15 to 40 degrees C, LPD
      decreased from 13.5 to 0.75 h and MPD reached 0.27-2.2 x1 0(9) CFU/ml in YSU and
      WE, respectively. Markedly lower growth was observed in YSA (LPD=24-270 h, MPD=9
      x 10(5) CFU/ml) and spores were inactivated completely within 1-6h in EW. The
      survivability and inactivation data of B. anthracis in liquid egg products
      reported in this investigation will be helpful in developing risk assessment
      models on food biosecurity.

PMID- 19171253
TI  - Description of the microflora of sourdoughs by culture-dependent and culture
      independent methods.
AB  - Four types of sourdoughs (L, C, B, Q) from artisanal bakeries in Northern Italy
      were studied using culture-dependent and culture-independent methods. In all
      samples, the yeast numbers ranged from 160 to 10(7)cfu/g, and the numbers of
      lactic acid bacteria (LAB) ranged from 10(3) to 10(9)cfu/g. The isolated LAB were
      sequenced, and a similarity was noted between two samples (C, Q), both in terms
      of the species that were present and in terms of the percentage of isolates. In
      these two samples, Lactobacillus plantarum accounted for 73% and 89% of the
      bacteria, and Lactobacillus brevis represented 27% and 11%. In the third sample
      (B), however, the dominant LAB isolate was Lb. brevis (73%), while Lb. plantarum
      accounted for only 27%. The fourth sourdough (L) was completely different from
      the others. In this sample, the most prominent isolate was Weisella cibaria
      (56%), followed by Lb. plantarum (36%) and Pediococcus pentosaceus (8%). In three
      out of four samples (L, C and Q), all of the yeasts isolated were identified as
      Saccharomyces cerevisiae, yet only Candida humilis (90%) and Candida milleri
      (10%) were isolated in the fourth sample (B). The microbial ecology of the
      sourdoughs was also examined with direct methods. The results obtained by culture
      independent methods and DGGE analysis underline a partial correspondence between
      the DNA and RNA analysis. These results demonstrate the importance of using a
      combined analytical approach to explore the microbial communities of sourdoughs.

PMID- 19171254
TI  - Spontaneous fermentation of traditional sago starch in Papua New Guinea.
AB  - Sago starch is an important dietary carbohydrate in lowland Papua New Guinea
      (PNG). An investigation was conducted to determine whether microbes play a role
      in its preservation using traditional methods. In 12 stored sago samples
      collected from PNG villages, lactic acid bacteria (LAB) were present (> or = 3.6
      x 10(4)cfu/g) and pH ranged from 6.8 to 4.2. Acetic and propionic acids were
      detected in all samples, while butyric, lactic and valeric acids were present in
      six or more. In freshly prepared sago, held in sealed containers in the
      laboratory at 30 degrees C, spontaneous fermentation by endogenous microflora of
      sago starch was observed. This was evident by increasing concentrations of
      acetic, butyric and lactic acids over 4 weeks, and pH reducing from 4.9 to 3.1:
      both LAB and yeasts were involved. Survival of potential bacterial pathogens was
      monitored by seeding sago starch with approximately 10(4)/g of selected
      organisms. Numbers of Bacillus cereus, Listeria monocytogenes and Staphylococcus
      aureus fell to < 30/g within 7 days. Salmonella sp. was present only in low
      numbers after 7 days (< 36/g), but Escherichia coli was still detectable after
      three weeks (> 10(2)/g). Fermentation appeared to increase the storability and
      safety of the product.

PMID- 19171255
TI  - Antimicrobial activity of plant essential oils using food model media: efficacy,
      synergistic potential and interactions with food components.
AB  - The aim of this study was to optimise the antimicrobial efficacy of plant
      essential oils (EOs) for control of Listeria spp. and spoilage bacteria using
      food model media based on lettuce, meat and milk. The EOs evaluated were lemon
      balm, marjoram, oregano and thyme and their minimum inhibitory concentrations
      (MIC) were determined against Enterobacter spp., Listeria spp., Lactobacillus
      spp., and Pseudomonas spp. using the agar dilution method and/or the absorbance
      based microplate assay. MICs were significantly lower in lettuce and beef media
      than in TSB. Listeria strains were more sensitive than spoilage bacteria, and
      oregano and thyme were the most active EOs. EO combinations were investigated
      using the checkerboard method and Oregano combined with thyme had additive
      effects against spoilage organisms. Combining lemon balm with thyme yielded
      additive activity against Listeria strains. The effect of simple sugars and pH on
      antimicrobial efficacy of oregano and thyme was assessed in a beef extract and
      tomato serum model media. EOs retained greater efficacy at pH 5 and 2.32% sugar,
      but sugar concentrations above 5% did not negatively impact EO efficacy. In
      addition to proven antimicrobial efficacy, careful selection and investigation of
      EOs appropriate to the sensory profile of foods and composition of the food
      system is required. This work shows that EOs might be more effective against food
      borne pathogens and spoilage bacteria when applied to foods containing a high
      protein level at acidic pH, as well as moderate levels of simple sugars.

PMID- 19171256
TI  - Use of natural compounds to improve the microbial stability of Amaranth-based
      homemade fresh pasta.
AB  - A study on the use of natural antimicrobial compounds to improve the
      microbiological stability of refrigerated amaranth-based homemade fresh pasta is
      presented in this work. In particular, the antimicrobial activity of thymol,
      lemon extract, chitosan and grapefruit seed extract (GFSE) has been tested
      against mesophilic and psychrotrophic bacteria, total coliforms, Staphylococcus
      spp., yeasts and moulds. A sensory analysis on both fresh and cooked pasta was
      also run. Results suggest that chitosan and GFSE strongly increase the microbial
      acceptability limit of the investigated spoilage microorganisms, being the former
      the most effective. Thymol efficiently reduces the growth of mesophilic bacteria,
      psychrotrophic bacteria and Staphylococcus spp., whereas it does not affect,
      substantially, the growth cycle of total coliforms. Lemon extract is the less
      effective in preventing microbial growth. In fact, it is able to delay only total
      mesophilic and psychrotrophic bacterial evolution. From a sensorial point of view
      no significant differences were recorded between the control samples and all the
      types of loaded amaranth-based pasta.

PMID- 19171257
TI  - Effects of gamma-irradiation on Listeria monocytogenes population, colour,
      texture and sensory properties of Feta cheese during cold storage.
AB  - Feta, a white brine cheese, was produced and contaminated with Listeria
      monocytogenes. Contamination occurred either at the beginning (pre-process
      contamination) or at the end of Feta manufacturing (post-process contamination).
      In the first case the milk was contaminated with 10(3) cfu/ml, and 2 months
      later, in the final product, the L. monocytogenes population was approximately
      10(5) cfu/g. In the second case, the brine (NaCl, 7% w/v), in which the Feta was
      packaged, was contaminated with 10(3) cfu/ml. Contaminated Feta samples were
      vacuum-packaged and exposed to irradiation doses of 1.0, 2.5 and 4.7 kGy and
      stored at 4 degrees C for a month. In the pre-process contaminated samples none
      of the irradiation doses eliminated L. monocytogenes; however the highest dose
      reduced the viable population to a level which is in compliance with EC
      regulations. In the post-process contamination, the 2.5 kGy and 4.7 kGy doses
      reduced L. monocytogenes counts below the detection limit. Irradiation had no
      effect on the texture of Feta. Irradiation at 4.7 kGy increased Feta's redness
      and decreased its yellowness and lightness. Sensorial analyses showed that at the
      4.7 kGy dose, the aroma profile of Feta was temporarily affected, since it was
      restored after 30 days of cold storage.

PMID- 19171258
TI  - Combined effect of vacuum-packaging and oregano essential oil on the shelf-life
      of Mediterranean octopus (Octopus vulgaris) from the Aegean Sea stored at 4
      degrees C.
AB  - The present study evaluated the use of vacuum packaging (alone) or with addition
      of oregano essential oil (EO), as an antimicrobial treatment for shelf-life
      extension of fresh Mediterranean octopus stored under refrigeration for a period
      of 23 days. Four different treatments were tested: A, control sample; under
      aerobic storage in the absence of oregano essential oil; VP, under vacuum
      packaging in the absence of oregano essential oil; and VO1, VO2, treated samples
      with oregano essential oil 0.2 and 0.4% (v/w), respectively, under VP. Of all the
      microorganisms enumerated, Pseudomonas spp., H2S-producing bacteria and lactic
      acid bacteria (LAB) were the groups that prevailed in octopus samples,
      irrespective of antimicrobial treatment. With regard to the chemical freshness
      indices determined, thiobarbituric acid (TBA) values were low in all octopus
      samples, as could have been expected from the low fat content of the product.
      Both trimethylamine nitrogen (TMA-N) and total volatile basic nitrogen (TVB-N)
      values of oregano treated under VP octopus samples were significantly lower
      compared to control samples during the entire refrigerated storage period. Based
      primarily on sensory evaluation (odor), the use of VP, VO1 and VO2 extended the
      shelf-life of fresh Mediterranean octopus by ca. 3, 11 and 20 days, respectively.

PMID- 19171259
TI  - Prevalence and characterization of Escherichia coli O157:H7 isolates from meat
      and meat products sold in Amathole District, Eastern Cape Province of South
      Africa.
AB  - Meat and meat products have been implicated in outbreaks of Escherichia coli
      O157:H7 in most parts of the world. In the Amathole District Municipality of the
      Eastern Cape Province of South Africa, a large number of households consume meat
      and meat products daily, although the microbiological quality of these types of
      food is questionable. The present study investigated the prevalence of E. coli
      O157:H7 isolated from selected meat and meat products (45 samples each of
      biltong, cold meat, mincemeat, and polony) sold in this area. Strains of E. coli
      O157:H7 were isolated by enrichment culture and confirmed by polymerase chain
      reaction (PCR). Also investigated were the antibiogram profiles of the E. coli
      O157:H7 isolates. Five (2.8%) out of 180 meat and meat products examined were
      positive for E. coli O157:H7 that carried the fliC(H7), rfbE(O157), and eaeA
      genes. Two of the E. coli O157:H7 isolates were resistant against all the eight
      antibiotics tested. To prevent E. coli O157:H7 infections, meat and meat products
      such as biltong, cold meat, mincemeat and polony should be properly handled, and
      packed in sterile polyvinyl wrappers.

PMID- 19171260
TI  - Salmonella, Escherichia coli O157:H7 and E. coli biotype 1 in a pilot survey of
      imported and New Zealand pig meats.
AB  - A pilot survey for the pathogens Salmonella and Escherichia coli O157:H7, and E.
      coli biotype 1 was conducted on 100 New Zealand-produced (domestic) pig carcasses
      and 110 imported pig meat samples over an 8-month period to assess the likelihood
      of introduction of novel pathogen strains into New Zealand (NZ), and as a guide
      for development of a domestic pork National Microbiological Database programme.
      Salmonella was not isolated from domestic pig carcasses or from pig meat imported
      from Canada and the USA. The prevalence of Salmonella in imported pig meat was
      3.6% (95% CI 1.0-9.0) with positive samples detected from Australian pig meat.
      The prevalence of E. coli O157:H7 on domestic pig carcasses was 1% (95% CI 0.03
      5.4) while the overall prevalence of E. coli O157:H7 in imported pig meat was
      1.8% (95% CI 0.2-6.4), detected mainly from Australian but not from Canadian or
      US pork. All except three samples have an E. coli biotype 1 count of < 100 CFU
      cm(-2) or g(-1), indicating good hygiene quality of domestic and imported pig
      meat. The results demonstrated that importation of uncooked pig meat is a
      potential route for the introduction of new clones of Salmonella and E. coli
      O157:H7 into New Zealand.

PMID- 19171261
TI  - Effect of mesophilic lactobacilli and enterococci adjunct cultures on the final
      characteristics of a microfiltered milk Swiss-type cheese.
AB  - The effect of four associations of adjunct cultures composed of mesophilic
      lactobacilli and enterococci, either solely or combined, on the microbiological,
      biochemical and sensory characteristics of Swiss-type cheese made using
      microfiltered cows' milk and supplemented with propionibacteria was studied. The
      global pattern of growth was similar to that generally observed in raw milk
      cheese and interactions between microflora were highlighted during ripening.
      Enterococci, which negatively affected the survival of streptococci starters,
      seemed to play a limited role in the formation of volatile compounds, probably
      due to their low levels throughout ripening. On the contrary, mesophilic
      lactobacilli, which affected the evolution of propionibacteria, enterococci and
      L. delbrueckii subsp. lactis starter counts, modified free amino acid content,
      production of volatile compounds and organoleptic properties of mature cheese.
      This population appeared to be of major importance in the formation of cheese
      flavor as it was positively related to numerous potential flavor compounds such
      as alcohols and their corresponding esters, acetaldehyde and 4-methyl-4
      heptanone. The original mesophilic lactobacilli present in milk could play an
      important role in the sensorial diversity of raw milk Swiss-type cheeses such as
      Comte.

PMID- 19171262
TI  - Quality assessment of lager brewery yeast samples and strains using barley malt
      extracts with anti-yeast activity.
AB  - Membrane active anti-yeast compounds, such as antimicrobial peptides and
      proteins, cause yeast membrane damage which is likely to affect yeast vitality
      and fermentation performance, parameters which are notoriously difficult to
      analyse. In this work the sensitivity of lager brewery yeast strains towards
      barley malt extracts with anti-yeast activity was assessed with an optimised
      assay. It was found that yeast, obtained directly from a brewery, was much more
      sensitive towards the malt extracts than the same yeast strain propagated in the
      laboratory. Sensitivity to the malt extracts increased during the course of a
      laboratory scale fermentation when inoculated with brewery yeast. As the assay
      was able to differentiate yeast samples with different histories, it shows
      promise as a yeast quality assay measuring the yeast's ability to withstand
      stress which can be equated to vitality. The assay was also able to differentiate
      between different lager yeast strains of Saccharomyces cerevisiae propagated in
      the laboratory when challenged with a number of malt extracts of varying anti
      yeast activity. The assessment of yeast strains in the presence of malt extracts
      will lead to the identification of yeast strains with improved quality/vitality
      that can withstand malt-associated anti-yeast activity during brewery
      fermentations.

PMID- 19171263
TI  - Influence of ethanol and pH on the gene expression of the citrate pathway in
      Oenococcus oeni.
AB  - The consumption of citrate by the malolactic bacterium Oenococcus oeni changes
      the aromatic profile of wines due to the production of volatile compounds such as
      diacetyl and acetic acid. In this study, the expression of genes related to
      citrate utilization in the O. oeni strain PSU-1 was investigated to further
      understand the role of this metabolic pathway in the adaptation to wine
      environment and its impact on organoleptic qualities. Different conditions of
      ethanol content (0% and 10%) and pH (3.5 and 4.0) were assayed to evaluate the
      transcriptional response to both these stress factors. In the presence of
      ethanol, metabolic and transcriptional behavior was different than the observed
      when ethanol was absent. The expression of citrate pathway genes was mainly
      affected by ethanol, while pH showed a lower effect. Among the studied genes,
      citE, ackA and alsD were the genes revealing a distinctive transcriptional
      response. The differences observed in gene expression were in correlation with
      the different content of end products such as acetic acid and diacetyl. The
      increment of gene expression observed in the presence of ethanol at low pH
      suggests the participation of citrate metabolism in the response to stress
      conditions.

PMID- 19171264
TI  - The influence of yeast on the aroma of Sauvignon Blanc wine.
AB  - The main objective of this study was to investigate the effect of different
      Saccharomyces cerevisiae wine yeast strains on the concentration of aroma
      enhancing volatile thiols and fermentation metabolites in Sauvignon Blanc wine.
      Seven commercial wine yeast strains were selected based on their putative ability
      to modulate the concentrations of the fruity volatile thiols, 4-mercapto-4
      methylpentan-2-one (4MMP), 3-mercapto-hexanol (3MH) and 3-mercapto-hexylacetate
      (3MHA). Each of these yeasts was used to produce Sauvignon Blanc wines under
      controlled conditions, in triplicate, in 20-L quantities. The levels of 4MMP, 3MH
      and 3MHA in these wines were quantified using the p-hydroxymercuribenzoate
      method. In addition, a total of 24 volatile yeast-derived fermentation aroma
      compounds were also quantified using headspace solid-phase microextraction
      coupled with gas chromatography mass spectrometry (HS-SPME-GC-MS). Formal sensory
      analysis was conducted by 12 trained assessors and, additionally, a panel of 24
      experienced wine industry professionals assessed the wines and ranked them in
      order of preference. The results indicated that the yeast strains varied
      significantly in terms of their capabilities to (i) produce volatile thiols and
      fermentation metabolites; and (ii) to modulate the varietal characters of
      Sauvignon Blanc wine. Yeast strains that produced the highest levels of volatile
      thiols were responsible for wines with the highest perceived intensity of
      fruitiness, and these wines were preferred by the tasting panels. While the
      'green' characters in Sauvignon Blanc wines can be manipulated through vineyard
      management, the 'tropical fruity' characters appear to be largely dependent on
      the wine yeast strain used during fermentation. Therefore, the choice of yeast
      strain offers great potential to modulate wine aroma profiles to definable styles
      and predetermined consumer market specifications.

PMID- 19171265
TI  - Contributions to selected phenotypic characteristics of large species- and
      lineage-specific genomic regions in Listeria monocytogenes.
AB  - We hypothesized that genomic regions specific to Listeria monocytogenes or
      selected L. monocytogenes strains may contribute to virulence and phenotypic
      differences among the strains. A whole genome alignment of two completed L.
      monocytogenes genomes and the one completed Listeria innocua genome initially
      identified 28 genomic regions of difference (RD) > 4 kb that were found in one or
      both L. monocytogenes genomes, but absent from the non-pathogenic L. innocua. In
      silico analyses using an additional 18 draft L. monocytogenes genomes showed that
      (i) 15 RDs were found in all or most L. monocytogenes genomes; (ii) three RDs
      were found in all or most lineage I genomes, but absent from lineage II genomes;
      and (iii) four RDs were found in all lineage II genomes, but no lineage I
      genomes. Null mutants in two L. monocytogenes-specific RDs (RD16 and RD30; found
      in most L. monocytogenes) and the lineage II-specific RD25 showed no evidence for
      impaired invasion or intracellular growth in selected tissue culture cells.
      Although, in pH 5.5 minimal media, the DeltaRD30 null mutant showed reduced
      ability to compete with its parent strain, indicating that RD30 may have a role
      in L. monocytogenes growth under limited nutrient conditions at acidic pH.

PMID- 19171266
TI  - A comparison between E-beam irradiation and high pressure treatment for cold
      smoked salmon sanitation: microbiological aspects.
AB  - The effectiveness of electron beam irradiation and high pressure treatment for
      the sanitation of cold-smoked salmon from two points of view, microbial safety
      and shelf-life extension, was compared. From the response of L. monocytogenes
      INIA H66a to irradiation, a D value of 0.51 kGy was calculated. For samples
      stored at 5 degrees C, 1.5 kGy would be sufficient to attain a Food Safety
      Objective (FSO) of 2 log(10)cfu/g L. monocytogenes for a 35-day shelf-life,
      whereas 3 kGy would be needed in the case of a temperature abuse (5 degrees C + 8
      degrees C). Pressurization at 450 MPa for 5 min was considered to be an
      insufficient treatment, since the FSO of 2 log(10)cfu/g L. monocytogenes was only
      attained for a shelf-life of 21 days at 5 degrees C. However, treatment at 450
      MPa for 10 min achieved this FSO for samples held during 35 days at 5 degrees C,
      or during 21 days under temperature abuse (5 degrees C+8 degrees C) conditions.
      Irradiation at 2 kGy kept the microbial population of smoked salmon below 6
      log(10)cfu/g after 35 days at 5 degrees C, with negligible or very light changes
      in its odor. Pressurization at 450 MPa for 5 min also kept the microbial
      population below 6 log(10)cfu/g after 35 days at 5 degrees C and did not alter
      odor, but affected negatively the visual aspect of smoked salmon.

PMID- 19171267
TI  - Molecular identification of mesophilic and psychrotrophic bacteria from raw cow's
      milk.
AB  - The aim of this study was to use molecular techniques to assess the microbiota of
      eight raw cow's milk samples at biotype and species level. Sixty-six isolates
      from raw milk samples were screened by Randomly amplified polymorphic DNA-PCR
      (RAPD-PCR) biotyping and representative strains of RAPD-PCR profiles were
      identified by 16S rRNA gene sequencing. Pseudomonas spp. were the most commonly
      occurring contaminants along with Enterobacteriaceae such as Hafnia alvei,
      Serratia marcescens and Citrobacter freundii. Moreover, Gram-positive isolates
      belonging to the genera Staphylococcus and Lactococcus were also found.
      Experiments of growth at different temperatures showed that more than 50% of the
      Gram-negative isolates could grow at chill temperatures and that 65% of the
      Pseudomonas spp. strains grew at 7 degrees C within 5 days. Only 13 Gram-negative
      isolates displayed proteolytic activity on milk agar, suggesting that not all the
      biotypes of milk contaminating species are able to perform this spoilage
      associated activity. Among the Gram negative, the proteolytic strains were mainly
      Peudomonas spp. that displayed the activity at both 7 degrees C and 20 degrees C.
      A reliable molecular identification of raw milk microbiota is important for the
      study of the microbiological quality of raw milks and for the assessment of the
      ecology at species level in order to develop improved systems, preventing
      contamination and having the best conditions for the storage of milk.

PMID- 19171268
TI  - Saving our cells: advances in tissue engineering for focal cartilage defects.

PMID- 19171269
TI  - A minimum 2-year follow-up after selective anteromedial or posterolateral bundle
      anterior cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to investigate the 2-year follow-up
      clinical results of 45 patients who had undergone our anterior cruciate ligament
      (ACL) augmentation procedure using an autogenous semitendinosus tendon and the
      EndoButton CL (Smith & Nephew, Andover, MA). METHODS: We followed up 45 patients
      for more than 2 years after their ACL augmentations. Of these, 37 were
      anteromedial (AM) bundle reconstructions and 8 were posterolateral (PL) bundle
      reconstructions. They were assessed using a KT-2000 knee arthrometer (MEDmetric,
      San Diego, CA) at 30 lb by joint position sense, Lysholm knee score, and magnetic
      resonance imaging (MRI). RESULTS: The mean side-to-side difference of anterior
      displacement measured by the KT-2000 knee arthrometer at 30 degrees of knee
      flexion preoperatively was 3.3 +/- 2.4 mm, significantly improving to a mean of
      0.5 +/- 2.7 mm 2 years after surgery. The preoperative joint position sense
      inaccuracy was 1.6 degrees +/- 1.8 degrees , which improved significantly to 0.3
      degrees +/- 2.0 degrees after surgery. The median Lysholm knee score
      significantly improved from 74 (range, 44 to 95) to 100 points (range, 81 to 100)
      after surgery. In 20 of 29 patients who had the postoperative MRI examination,
      the augmented ACL resembled 1 bundle on the sagittal planes of the postoperative
      MRI. CONCLUSIONS: Selective AM or PL bundle reconstruction showed improved joint
      stability, joint position sense, and Lysholm scores postoperatively. This
      procedure can be a treatment option for patients whose ACL remnants are left in
      certain conditions.

PMID- 19171270
TI  - The effect of anterior cruciate ligament reconstruction on kinematics of the knee
      with combined anterior cruciate ligament injury and subtotal medial meniscectomy:
      an in vitro robotic investigation.
AB  - PURPOSE: The aims of this study were to determine: (1) the kinematic effect of
      subtotal medial meniscectomy on the anterior cruciate ligament (ACL)-deficient
      knee and (2) the effect of ACL reconstruction on kinematics of the knee with
      combined ACL deficiency and subtotal medial meniscectomy under anterior tibial
      and simulated quadriceps loads. METHODS: Eight human cadaveric knees were
      sequentially tested using a robotic testing system under 4 conditions: intact,
      ACL deficiency, ACL deficiency with subtotal medial meniscectomy, and single
      bundle ACL reconstruction using a bone-patellar tendon-bone graft. Knee
      kinematics were measured at 0 degrees, 15 degrees, 30 degrees, 60 degrees, and 90
      degrees of flexion under an anterior tibial load of 130 N and a quadriceps muscle
      load of 400 N. RESULTS: Subtotal medial meniscectomy in the ACL-deficient knee
      significantly increased anterior and lateral tibial translations under the
      anterior tibial and quadriceps loads (P < .05). These kinematic changes were
      larger at high flexion (>or=60 degrees) than at low flexion angles. ACL
      reconstruction in knees with ACL deficiency and subtotal medial meniscectomy
      significantly reduced the increased anterior tibial translation, but could not
      restore anterior translation to the intact level with differences ranging from
      2.6 mm at 0 degrees to 5.5 mm at 30 degrees of flexion. ACL reconstruction did
      not significantly affect the medial-lateral translation and internal-external
      tibial rotation in the presence of subtotal meniscectomy. CONCLUSIONS: Subtotal
      medial meniscectomy in knees with ACL deficiency altered knee kinematics,
      especially at high flexion angles. ACL reconstruction significantly reduced the
      increased tibial translation in knees with combined ACL deficiency and subtotal
      medial meniscectomy, but could not restore the knee kinematics to the intact knee
      level. CLINICAL RELEVANCE: This study suggests that meniscus is an important
      secondary stabilizer against anterior and lateral tibial translations and should
      be preserved in the setting of ACL reconstruction for restoration of optimal knee
      kinematics and function.

PMID- 19171271
TI  - Tubercular infection after arthroscopic anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: Tubercular infection has not been described, to our knowledge, in the
      literature after anterior cruciate ligament (ACL) reconstruction, and, hence, the
      purpose of our case series was to describe our experience, evaluate the clinical
      and laboratory findings, and assess the treatment outcome. METHODS: We performed
      a retrospective analysis of 1,152 cases of arthroscopic ACL reconstruction with
      autografts performed at our institution between January 1998 and May 2007.
      Tubercular infection was considered to be present in the setting of recurrent
      negative bacterial cultures but a positive result on microscopy, culture,
      histopathology, or polymerase chain reaction (PCR). All patients underwent
      arthroscopic lavage and synovectomy, followed by antitubercular therapy for 12
      months. RESULTS: We identified 8 patients (0.69%) with infection. Bone-patellar
      tendon-bone graft was used in 1 and hamstring graft in 7. All patients were
      immunocompetent. The mean time from surgery to presentation was 64.4 days (range,
      23 to 152 days). Aspirate fluid staining and culture for acid-fast bacilli was
      negative in all cases, synovial tissue culture was positive in 3, characteristic
      histopathology was positive in 7, and PCR was positive in 6. A mean of 1.25
      surgeries (range, 1 to 2) were performed. The mean length of follow-up in our
      series was 43.6 months (range, 25 to 73 months), with no reinfections. The mean
      postoperative Lysholm knee score was 80. CONCLUSIONS: Tubercular infection as a
      complication after arthroscopic ACL reconstruction, though rare, should be kept
      in mind as a possible cause of infection in immunocompetent patients in zones
      endemic for tuberculosis. It should also be kept in mind in nonendemic areas,
      among immigrants from endemic areas, and in cases with persistent swelling and
      discharge, effusion with minimal inflammatory signs, and negative cultures. We
      recommend deoxyribonucleic acid-PCR testing for early diagnosis of tuberculosis.
      Arthroscopic debridement and antitubercular chemotherapy together are the
      mainstay of treatment.

PMID- 19171272
TI  - Anterior cruciate ligament reconstruction: autogenous quadriceps tendon-bone
      compared with bone-patellar tendon-bone grafts at 2-year follow-up.
AB  - PURPOSE: The purpose of this study was to evaluate and compare postoperative
      anterior knee pain, knee stability, and functional scores of an autogenous bone
      patellar tendon-bone (BPTB) graft and a quadriceps tendon-bone (QTB) graft.
      METHODS: A total of 48 patients--27 who had anterior cruciate ligament (ACL)
      reconstruction by use of an autogenous BPTB graft and 21 who had ACL
      reconstruction by use of a QTB graft--were assessed at a minimum follow-up of 24
      months after surgery. An accelerated rehabilitation program was adapted, and the
      rehabilitation protocol was identical for both groups. RESULTS: The mean side-to
      side difference as measured with a KT-2000 arthrometer (MEDmetric, San Diego, CA)
      was 2.73 mm (SD, 1.45 mm) in the BPTB group and 2.79 mm (SD, 1.32 mm) in the QTB
      group (P = .880). Postoperatively, the International Knee Documentation Committee
      score was grade A or B in 23 patients (85.2%) in the BPTB group and 18 (85.7%) in
      the QTB group (P = .997). The mean anterior knee pain score was 86.9 in the BPTB
      group as compared with 90.2 in the QTB group (P = .107). In a kneeling posture,
      13 BPTB patients reported discomfort (moderate in 10 and severe in 3) whereas
      only 4 QTB patients had moderate discomfort (P = .029). No significant
      differences were found with regard to other activities surveyed. CONCLUSIONS: A
      QTB graft attached with the EndoPearl device (Linvatec, Largo, FL) appears to be
      an effective alternative for single-bundle ACL reconstruction. When followed with
      an accelerated rehabilitation program, reconstruction with a QTB graft provided
      knee stability comparable to a BPTB graft but with less kneeling pain than a BPTB
      graft.

PMID- 19171273
TI  - Functional and radiographic outcome of stable juvenile osteochondritis dissecans
      of the knee treated with retroarticular drilling without bone grafting.
AB  - PURPOSE: The purpose of this study was to evaluate the functional and
      radiographic outcome of retroarticular drilling for patients with juvenile
      osteochondritis dissecans after 6 months of unsuccessful nonoperative treatment.
      METHODS: A total of 20 osteochondritis dissecans lesions in 12 skeletally
      immature patients were treated with retroarticular drilling without bone
      grafting. There were 10 boys and 2 girls with a mean age of 12.0 years (range, 9
      to 15 years). The functional outcomes were evaluated by use of the Lysholm score
      at a mean follow-up of 2.7 years after drilling, and healing of the lesions was
      confirmed by use of plain radiographs and magnetic resonance imaging. RESULTS:
      The mean Lysholm score significantly improved postoperatively (from 72.3 to
      95.8). All lesions except 1 healed after retroarticular drilling. Healing was
      achieved at a mean of 4.4 months on plain radiographs and 7.6 months on magnetic
      resonance imaging. CONCLUSIONS: This study shows that retroarticular drilling
      without bone grafting leads to improved clinical outcomes and high healing rates.
      We advocate retroarticular drilling for patients with stable juvenile
      osteochondritis dissecans of the knee whose initial nonoperative treatment has
      failed.

PMID- 19171274
TI  - Arthroscopic elimination of monosodium urate deposition of the first
      metatarsophalangeal joint reduces the recurrence of gout.
AB  - PURPOSE: To determine if the arthroscopic removal of gouty crystal deposits from
      the first metatarsophalangeal (MTP) joint will reduce the recurrence rate and
      improve foot function compared to medical treatment alone. METHODS: Twenty-eight
      male patients with hyperuricemia (>7.0 mg/dL) and repeated attacks of gouty
      arthritis of the first MTP joint were included in this study. Arthroscopic
      intervention of the first MTP joint was performed on 15 patients (group 1), while
      the other 13 patients were treated with medication alone (group 2). The follow-up
      period (mean +/- standard deviation) was 3.9 +/- 1.1 years in group 1 and 2.4 +/-
      0.3 years in group 2. RESULTS: After treatment, both groups showed a significant
      improvement in the number of acute attacks of gouty arthritis and in their
      functional scores on the American Orthopaedic Foot and Ankle Society Ankle
      Hindfoot Scale. On both measures, the results for group 1 were significantly
      better than those for group 2. CONCLUSIONS: Arthroscopic removal of gouty
      crystals from the first MTP joint can reduce the rate of acute repeated attacks
      of gouty arthritis and increase foot and ankle function.

PMID- 19171275
TI  - Prospective randomized study of 2 different techniques for endoscopic iliopsoas
      tendon release in the treatment of internal snapping hip syndrome.
AB  - PURPOSE: To evaluate the short-term results of 2 different techniques of
      endoscopic iliopsoas tendon release for the treatment of internal snapping hip
      syndrome. METHODS: Between January 2005 and January 2007, a consecutive series of
      patients with the diagnosis of internal snapping hip syndrome was treated with
      endoscopic release of the iliopsoas tendon. The patients were randomized into 2
      different groups. Patients in group 1 were treated with endoscopic iliopsoas
      tendon release at the lesser trochanter, and patients in group 2 were treated
      with endoscopic transcapsular psoas release from the peripheral compartment. Hip
      arthroscopy of both the central and peripheral compartments was performed in both
      groups using the lateral approach. Associated injuries were identified and
      treated arthroscopically. Postoperative physical therapy was the same for both
      series, and each patient received 400 mg of celecoxib daily for 21 days after
      surgery. Preoperative and postoperative Western Ontario MacMaster (WOMAC) scores
      and imaging studies were evaluated. RESULTS: Nineteen patients were included in
      the study: 10 in group 1 (5 male and 5 female; average age, 29.5 years) and 9 in
      group 2 (8 female and 1 male; average age, 32.6 years). No statistical difference
      was found in group composition. Associated injuries were found and treated in 8
      patients in group 1 and 7 patients in group 2. No statistical difference was
      found between groups in preoperative WOMAC scores, and every patient in both
      groups had an improvement in the WOMAC score. Improvements in WOMAC scores were
      statistically significant in both groups, and no difference was found in
      postoperative WOMAC results between groups. No complications were seen.
      CONCLUSIONS: Iliopsoas tendon release at the level of the lesser trochanter or at
      the level of the hip joint using a transcapsular technique is effective and
      reproducible. We found no clinical difference in the results of both techniques.

PMID- 19171276
TI  - How accurately can the acetabular rim be trimmed in hip arthroscopy for pincer
      type femoral acetabular impingement: a cadaveric investigation.
AB  - PURPOSE: The purpose of this study was to evaluate the precision of central hip
      arthroscopy in the assessment and treatment of pincer-type femoroacetabular
      impingement (FAI) avoiding the posterolateral portal, with its close proximity to
      the main arterial blood supply of the femoral head, the medial circumflex femoral
      artery. METHODS: Seven human cadaveric hips underwent arthroscopic trimming of
      the acetabular labrum and rim along a preoperatively defined 105 degrees arc of
      resection for treatment of a presumed pincer-type lesion. After the arthroscopic
      procedure, all specimens were dissected and measured for evaluation of the
      location, quantity, and quality of the area undergoing resection. RESULTS: The
      difference between the actual and planned arc of resection was 18.7 degrees +/-
      4.7 degrees (range, 2 degrees to 34 degrees). This was mainly because of a lack
      of accuracy in the presumed posterior starting point (PSP), with a mean deviation
      of 19 degrees +/- 3.4 degrees (range, 10 degrees to 36 degrees). Correlation
      analysis showed that variance in the arc of resection was mainly dependent on the
      PSP (r = 0.739, P = .058). CONCLUSIONS: Central hip arthroscopy is a feasible
      option in treating anterosuperior pincer-type FAI by use of the anterior and
      anterolateral portals only. This cadaveric study showed that there is a
      significant risk of underestimating the actual arc of resection compared with the
      planned arc of resection for posterosuperior pincer-type lesions because of the
      modest accuracy in determining the PSP of the resection. CLINICAL RELEVANCE:
      Accurate preoperative planning and arthroscopic identification of anatomic
      landmarks at the acetabular side are crucial for the definition of the
      appropriate starting and ending points in the treatment of pincer-type FAI.
      Whereas anterosuperior pincer-type lesions can be addressed very precisely with
      our technique, the actual resection of posterosuperior lesions averaged 19
      degrees less than the planned resection, which may have clinical implications.

PMID- 19171277
TI  - Arthroscopic findings following traumatic hip dislocation in 14 professional
      athletes.
AB  - PURPOSE: The purpose of this study was to investigate intra-articular hip joint
      pathologies in professional athletes who sustained dislocation and were treated
      with hip arthroscopy. METHODS: Between August 23, 2000, and September 15, 2006,
      14 professional athletes (12 male and 2 female) sustained a nonfracture traumatic
      hip dislocation during active competition and were treated by a single surgeon. A
      retrospective chart review of this cohort was done to report the intra-articular
      hip pathologies identified at the time of arthroscopy. RESULTS: The average time
      from dislocation to relocation was 3.56 hours. The mean time from dislocation to
      surgery was 125 days (range, 0 to 556 days). The average age at the time of
      arthroscopy was 30.5 years (range, 16 to 46 years). All patients had labral
      tears. All patients had chondral defects. Two had isolated femoral head chondral
      defects, 6 had isolated acetabular chondral defects, and 6 had chondral defects
      on both surfaces. Eleven patients had loose osteochondral fragments. Eleven
      patients had partial or complete tears of the ligamentum teres. Nine patients had
      evidence of femoroacetabular impingement; 4 had isolated cam lesions, 1 had an
      isolated pincer lesion on the acetabular rim, and 4 patients had mixed type
      pathology. Two patients had capsulolabral adhesions. Two patients had a capsular
      tear. Additionally, 3 patients underwent intraoperative evaluation of the lateral
      epiphyseal vessels with Doppler imaging to confirm good blood flow to the femoral
      head with consistent pulse. CONCLUSIONS: The results of this study show that
      traumatic dislocation is accompanied by a variety of intra-articular hip joint
      pathologies, the most common being labral, chondral, intra-articular loose
      fragments, and disruption of the ligamentum teres.

PMID- 19171278
TI  - Surgical correction of "cam-type" femoroacetabular impingement: a cadaveric
      comparison of open versus arthroscopic debridement.
AB  - PURPOSE: The goal of this study was to compare open and arthroscopic surgical
      techniques for "cam-type" femoroacetabular impingement in terms of feasibility
      and reliability. METHODS: We used 5 fresh-frozen cadaver specimens (10 hips).
      Anteroposterior and cross-table radiographs were taken for each. The head-neck
      union diameter was measured for each. The amount of bone resection at the
      anterolateral quadrant of the head-neck union was planned for each, with specific
      references to width, length, depth, and position. One side was randomly assigned
      to the open group and the other to the arthroscopic group. Surgical time,
      position of the osteotomy, and variation of the length, width, and depth of the
      final osteotomy with respect to the proposed dimensions were compared. RESULTS:
      In all specimens partial resection of the anterior-lateral femoral head-neck
      junction with improvement of the femoral head-neck offset was accomplished. A
      statistically significant difference (P < .05) was observed for surgical time
      between the open and arthroscopic groups (shorter in open group). CONCLUSIONS:
      When comparing surgical precision, no statistically significant differences were
      found between the open and arthroscopic procedures in any of the measurements.
      The depth and width of the osteoplasty were reliably obtained by the arthroscopic
      technique. However, there was a tendency to underestimate the osteoplasty length
      with the arthroscopic procedure. Positioning the osteoplasty was also less
      reliable with the arthroscopic procedure than with the open procedure because of
      the tendency to place the osteoplasty more posterior and distally than intended.
      CLINICAL RELEVANCE: Surgical resection of the femoral neck prominence and/or part
      of the anterolateral neck has been reported to improve femoral head offset and
      alleviate impingement. This study attempts to document the accuracy of this
      resection when done arthroscopically compared with an open procedure.

PMID- 19171280
TI  - Cyclic load and failure behavior of arthroscopic knots and high strength sutures.
AB  - PURPOSE: To compare the biomechanical performance of several different sutures by
      evaluating knot security and load to failure strength using different
      arthroscopic knots. METHODS: Eight different No. 2 sutures (Ethibond [Ethicon,
      Somerville, NJ], FiberWire [Arthrex, Naples, FL], Orthocord [DePuy-Mitek,
      Norwood, MA], Hi-Fi [ConMed Linvatec, Largo, FL], Ultrabraid [Smith & Nephew,
      Andover, MA], ForceFiber [Stryker Endoscopy, San Jose, CA], MagnumWire
      [ArthroCare, Sunnyvale, CA], and MaxBraid PE [Arthrotek, Warsaw, IN]) were tied
      arthroscopically into standardized loops using 6 different knots (Weston,
      Tennessee slider, Duncan, SMC, Revo, and San Diego knot) 10 times each. The
      suture loops were pretensioned to 10N, cycled between 10N and 45N for 1,000
      cycles, and loaded to failure. The failure load for each suture, each knot, and
      slippage trend during cyclic loading was recorded. RESULTS: The Revo and SMC
      knots (group A) were stronger than the Tennessee and San Diego knots (group B),
      which were stronger than the Weston knot, which was stronger than the Duncan loop
      (P < .05). This pattern also coincided with the loads at which these knots
      slipped. Evaluating the sutures showed that Ethibond had lower failure loads than
      all other sutures and FiberWire showed statistically higher loads (P < .05).
      Duncan loops (97.5%) and Weston knots (86.3%) slipped more than other knots (P <
      .001), while the SMC and Revo knots slipped least. Ethibond sutures were least
      likely to slip. CONCLUSIONS: The Duncan loop and Weston knot were more likely to
      slip than all other knots, and caution should be exercised when tying them with
      high-strength sutures. The Revo, Tennessee slider, San Diego, and SMC knots were
      least likely to slip (P < .001). CLINICAL RELEVANCE: While stronger than braided
      polyester sutures, newer sutures containing ultra-high molecular weight
      polyethylene have a greater tendency to slip. Backing up knots with 4 reversed
      half hitches with switched posts does not guarantee knot security.

PMID- 19171279
TI  - Arthroscopic biceps augmentation for avoiding undue tension in repair of massive
      rotator cuff tears.
AB  - PURPOSE: The purpose of our study was to evaluate the outcome of massive rotator
      cuff tears repaired by use of an arthroscopic biceps augmentation technique,
      interpositioning the tenotomized biceps tendon to bridge the gap between the torn
      edges of the cuff tendon. METHODS: Sixty-eight shoulders with massive rotator
      cuff tears were included in this study. Arthroscopic rotator cuff repairs with
      the biceps augmentation technique were performed in 37 patients (group A),
      whereas 31 patients underwent repair without biceps augmentation (group B). The
      mean follow-up period was 21 months (range, 14 to 78 months) in group A and 20
      months (range, 13 to 63 months) in group B. RESULTS: The mean University of
      California, Los Angeles score improved from 14.1 points (range, 6 to 21 points)
      in group A and 13.9 points (range, 7 to 22 points) in group B preoperatively to
      32.6 points (range, 22 to 35 points) and 30.3 points (range, 20 to 35 points)
      postoperatively, respectively (P < .001 and P < .001, respectively). However, the
      difference between the postoperative scores was not statistically significant (P
      = .198). At the last follow-up, group A showed better results than group B in
      forward flexion, external rotation, and internal rotation strength, with
      statistically significant differences (P = .017, P = .001, and P < .001,
      respectively). According to the postoperative repair integrity analyzed by use of
      magnetic resonance imaging, 58.3% of group A cases (14/24) and 26.3% of group B
      cases (5/19) had complete healing (P = .036). CONCLUSIONS: An arthroscopic
      augmentation technique using the tenotomized biceps tendon was effective in
      achieving fewer structural failures, equivalent clinical outcomes, and
      significant improvement in muscle strength in comparison traditional arthroscopic
      repairs by avoiding undue tension in cases with massive rotator cuff tear.

PMID- 19171282
TI  - New technique for cell-seeded collagen-matrix-supported autologous chondrocyte
      transplantation.
AB  - Autologous chondrocyte transplantation/implantation (ACT/ACI) is becoming
      increasingly common for the treatment of large cartilage defects in the knee
      joint. The traditional ACT technique involves injection of a suspension of cells
      into the cartilage defect, which is covered with a periosteal flap or collagen
      membrane. The technique requires extensive suturing to create an effective seal;
      however, cell leakage remains a potential problem. Matrix-induced autologous
      chondrocyte implantation (MACI/MACT) avoids this potential problem by using a
      membrane on which chondrocytes are seeded and cultured for several days, before
      the membrane is cut to the correct size and shape of the defect. Time-consuming
      extensive suturing is unnecessary. However, cutting and repeated manipulation of
      the seeded membrane may result in the loss of critical chondrocytes. A modified
      technique termed ACT-collagen membrane seeding (ACT-Cs) has been developed in
      which expanded chondrocytes are applied to the collagen membrane after it has
      been cut to size, substantially reducing the risk of viable cell loss while
      retaining the ease and speed of the MACI/MACT procedure. In addition, the seeding
      of mitotically active chondrocytes onto the membrane after expansion and
      immediately before transplantation allows direct application of high cell
      concentrations.

PMID- 19171281
TI  - Graft tensioning in anterior cruciate ligament reconstruction: a systematic
      review of randomized controlled trials.
AB  - PURPOSE: The purposes of this study were to (1) perform a systematic review of
      randomized controlled trials evaluating graft tensioning in anterior cruciate
      ligament (ACL) reconstruction, and (2) determine the scientific quality of
      published randomized controlled trials evaluating graft tensioning in ACL
      reconstruction. METHODS: The search strategy included a computerized literature
      search, a citation search, and a manual search of key journals and conference
      proceedings. Eligible studies were randomized controlled trials evaluating the
      effect of graft tensioning on the outcomes of ACL reconstruction. Two reviewers
      independently performed the literature searches. The validity of the trials was
      scored using the Detsky quality scale. Consensus was achieved by a study
      committee of 3 investigators. RESULTS: Five randomized controlled trials met the
      inclusion criteria. The mean standardized Detsky score was 61.3 +/- 15.2%. Only 2
      of the studies scored >or=75%. All trials consisted of autogenous graft sources,
      with 3 involving a bone-patellar tendon-bone graft, 1 involving a 5-strand
      semitendinosus-polyester (5STP) graft, and 1 involving a semitendinosus-gracilis
      polyester (STGP) graft. CONCLUSIONS: Based on the evidence in this systematic
      review, there is a trend that suggests that 80 N of tension is the most effective
      amount of tension to apply during ACL reconstruction using hamstring-polyester
      graft sources. For ACL reconstruction using semitendinosus-gracilis or patellar
      tendon graft sources, there is no clear trend in terms of statistically
      significant or clinically relevant differences in terms of the amount of applied
      tension to apply to the graft during graft fixation. We are unable to provide
      recommendations as to the amount of tension to apply to 4-strand semitendinosus
      gracilis autografts without polyester augmentation because there has been no
      randomized clinical trial conducted to determine the most effective amount of
      tension to apply when using this graft source.

PMID- 19171283
TI  - Laser-guided placement of the tibial guide in the transtibial technique for
      anterior cruciate ligament reconstruction.
AB  - In anterior cruciate ligament (ACL) reconstruction, it is important to determine
      the location and direction of the femoral bone tunnel when using the transtibial
      technique. Accurately identifying the anatomic location at which to make the
      femoral bone tunnel for double-bundle ACL reconstruction is not a straightforward
      procedure. We describe a new method in which the centrum of the femoral tunnel is
      marked with an awl and a laser beam-guided technique is used to place the tibial
      pin. This procedure allows us to mark the desired location of the femoral tunnel
      before drilling the tibial bone tunnel when using the transtibial technique. This
      is the first report of a laser-guided technique used in arthroscopic surgery. We
      used a laser beam to determine the location of the femoral tunnel--the anatomic
      site needed to perform the intra-articular drilling in the tibia. In this
      technique, a laser pointer is set at the tibial guide, which reflects the laser
      beam and illuminates the point where the femoral bone tunnel should be made. Our
      method offers an easy and accurate way to reconfirm the tibial placement before
      drilling.

PMID- 19171284
TI  - Leg anterior compartment syndrome following ankle arthroscopy after Maisonneuve
      fracture.
AB  - We report a case of leg anterior compartment syndrome following ankle arthroscopy
      after Maisonneuve fracture. A 21-year-old football player sprained his left
      ankle. Plain radiography of his left ankle showed a lateral dislocation of the
      talus without obvious fractures. Plain radiography of his left lower extremity
      showed a spiral fracture of the proximal fibula approximately one third distal to
      the fibular head. According to these findings, we diagnosed this fracture as a
      Maisonneuve fracture and treated it by ankle arthroscopy and drilling of the
      talar osteochondral injury followed by arthroscopic ankle visualization during
      syndesmosis screw fixation. Six hours after surgery, the patient complained of
      pain in the lower extremity. We diagnosed acute compartment syndrome and
      performed emergent fasciotomy. One year after surgery, he was able to fully
      participate in athletic activities. We consider ankle arthroscopy to be available
      for the treatment of ankle fracture with the suspected complication of an intra
      articular disorder such as a Maisonneuve fracture. However, with this type of
      ankle fracture, there is a higher potential risk of acute compartment syndrome
      developing than with other types of ankle fractures. Therefore we suggest that
      surgeons guard against this complication.

PMID- 19171285
TI  - Unnecessary complication?

PMID- 19171287
TI  - Bone-bridge technique not new.

PMID- 19171288
TI  - Disciplinary custodians in nursing.

PMID- 19171289
TI  - Predicting cardiovascular risk using measures of regional and total body fat.
AB  - Excessive body fat is associated with increased risk for coronary heart disease
      (CHD). Various anthropometric methods are currently used to quantify regional and
      total body fat. The objectives of this study were to provide more insight into
      differences in cutoff points between methods for measuring total body fat and
      those for measuring regional body fat, independently and in combination, and to
      determine how well anthropometric and bioelectrical impedance methods of
      estimating body composition predict cardiovascular risk in a sample of unfit
      National Guard soldiers. Unfit healthy men (n = 123) and women (n = 32) between
      21 and 55 years old from the Army National Guard were assessed for total and
      regional body fat. After having their degree of total and regional body fat
      assessed, the participants were categorized by level of body fat and 10-year CHD
      risk. Comparisons and predictions were made between degree of total as well as
      regional body fat and 10-year CHD risk estimated from Framingham Heart Study
      equations. A significant positive relationship was observed between waist
      circumference and 10-year CHD risk in men. When controlling for age, waist
      circumference was predictive of 10-year CHD risk, contributing to 6.4% of the
      variance, whereas waist-to-hip ratio did not contribute to the model
      significantly. The results of this study show that waist circumference is the
      best measure for identifying unfit male individuals at risk for CHD.

PMID- 19171290
TI  - Treatment patterns and outcomes in a low-risk nurse-midwifery practice.
AB  - Childbirth, which represents more than 20% of all hospitalizations for women, is
      often accompanied by technical intervention, and identifying best practices is
      crucial. This study analyzed data entered into the Nurse-Midwifery Clinical Data
      Set (ACNM, 1990) to ascertain treatment patterns and associated outcomes, using
      Kane's Model of Treatment and Outcomes (Kane, R. L. [1997]. Understanding health
      care outcomes research. Gaithersburg, MD: Aspen Publishers, Inc.). Low-risk women
      (N = 510) received prenatal care from nurse-midwives and delivered at a
      university facility. Significant relationships were found between patient
      characteristics (age) and clinical factors (parity, body mass index, number of
      prenatal visits, comorbidities) and between treatment interventions (activity,
      intake, invasive monitoring) and outcomes (infant Apgar scores, complications).

PMID- 19171291
TI  - A home-based nurse-coached inspiratory muscle training intervention in heart
      failure.
AB  - People with heart failure (HF) are living longer but with disabling dyspnea that
      erodes quality of life (QOL). Decreased strength of inspiratory muscles (IMs) may
      contribute to dyspnea in HF, and inspiratory muscle training (IMT) has been shown
      to improve the strength of IMs. The purpose of this study was to determine the
      effects of a 3-month nurse-coached IMT program. Bandura's Self-Efficacy Theory
      directed nursing interventions. This randomized controlled trial employed an
      experimental group (IMT) and a control group (education). Data were collected
      during six home visits. Outcome measures included maximal inspiratory pressure,
      perceived dyspnea, self-efficacy, and health-related QOL. Significant differences
      in PI(max), dyspnea, and respiratory rate were found. Implications for further
      research and practice are discussed.

PMID- 19171293
TI  - Incidence of bone loss, falls, and fractures after Roux-en-Y gastric bypass for
      morbid obesity.
AB  - The objectives of this study were to determine the incidence of and associated
      risks for falls and fractures after gastric bypass surgery for morbid obesity and
      to determine the clinical signs of bone loss. The sample consisted of 167
      individuals at a mean age of 47 years (SD = 10). Ten participants (6%) reported a
      decrease in height since surgery, and 33 (20%) reported a decrease in height
      since they were 20 years old. Eight participants (5%) reported postoperative
      fractures. Twenty-three participants (13.8%) reported falling once since surgery,
      and 34 (20.4%) reported falling two or more times since surgery. Twelve
      participants reported a new diagnosis of osteoporosis postoperatively, and 1
      participant reported a new diagnosis of osteopenia. Sixty-seven percent (n = 112)
      of the participants were never advised to undergo a bone density test
      postoperatively. The findings from this study suggest that bone loss is a
      critical issue in this patient population, with 25% (n = 42) reporting a decrease
      in height, 8% (n = 13) reporting a new diagnosis of osteoporosis or osteopenia,
      and 5% (n = 8) reporting fractures during a mean postoperative interval of 2.4
      years. In addition, risk for skeletal fragility is profound in this cohort of
      individuals, with 34% (n = 57) indicating a history of one or more falls
      postoperatively. The results from this study clearly indicate a need for early
      recognition of bone loss in this population so that timely interventions can be
      initiated to prevent further loss and subsequent fractures.

PMID- 19171292
TI  - Mexican American elders' use of home care services.
AB  - Mexican American (MA) elders are more functionally impaired at younger ages than
      other elders yet use home care services (HCS) less. To determine the possible
      reasons, nine questionnaires were completed in Spanish or English by MA elders
      and caregivers living in southern Arizona (N = 280). Contextual, personal, and
      attitudinal factors were significantly associated with the use of HCS, and
      cultural/ethnic factors were significantly associated with confidence in HCS.
      Interventions should be designed and tested to increase the use of HCS by MA
      elders by increasing service awareness and confidence in HCS while preserving the
      expectations of familism and reducing caregiving burden.

PMID- 19171294
TI  - Intensive management program to improve glycosylated hemoglobin levels and
      adherence to diet in patients with type 2 diabetes.
AB  - This study investigated the effects of a diabetes outpatient intensive management
      program (DOIMP) on glycosylated hemoglobin (HbA(1)c) levels and adherence to
      diabetes control recommendations over a 12-week follow-up period for patients
      with diabetes. The DOIMP was composed of multidisciplinary diabetes education,
      complication monitoring, and telephone counseling. Twenty-five patients in the
      intervention group participated in the DOIMP, whereas 24 in the control group
      were briefed on the conventional description of diabetes mellitus by diabetes
      education nurses. Patients in the intervention group decreased their mean HbA(1)c
      levels by 2.3%, as compared with 0.4% in the control group. There was a
      significant increase in adherence to diet for the intervention group as compared
      with the control group. These findings indicate that the DOIMP can improve
      HbA(1)c levels and adherence to diet in patients with type 2 diabetes.

PMID- 19171295
TI  - The relationship of nurses' professional characteristics to levels of clinical
      nursing expertise.
AB  - Many hospitals are searching for guidelines for professional practice models,
      which are a requirement for Magnet recognition. This study was undertaken to
      determine the professional nursing characteristics that may contribute to the
      development of clinical nursing expertise. Experience as an RN was found to be
      highly correlated with initial level of expertise. Educational preparation and
      certification were not correlated with expertise. This research suggests that
      nurses may require more on-the-job experience for the development of clinical
      nursing expertise than what has been reported in the literature.

PMID- 19171296
TI  - Normative salivary cortisol values and responsivity in children.
AB  - This was a descriptive study on normative salivary cortisol values and
      responsivity to a hospital clinic visit and an intravenous (IV) procedure in
      children. The study presented was a subproject of a primary research study that
      examined parents coaching their children requiring an IV placement in the use of
      distraction. One measure of child response in the primary study, salivary
      cortisol, was included to further our understanding of children's physiologic
      response to stressful and painful stimuli. Salivary cortisol samples were
      obtained from 384 children aged between 4 and 10 years upon arrival to the clinic
      and 20 minutes after their IV insertion. Baseline samples were collected at home
      on a typical day for the children. Data from baseline samples were used to
      establish normative values between 8:00 a.m. and 3:00 p.m. on a nonprocedural
      day. Results demonstrate that normative cortisol levels in children follow a
      pattern similar to the circadian pattern in adults, decreasing from early morning
      to mid afternoon. Matched samples from control group children were used to
      evaluate group responsivity. Salivary cortisol levels on the baseline day were
      lower than those obtained during the day of the procedure and tapered over time
      as expected (-8.7% +/- 6.7%, p = .431). Cortisol levels on the clinic day
      increased from baseline and increased further in response to IV placement (15.7%
      +/- 6.7%, p = .023). A Location x Time interaction was significant (p = .019).
      Findings demonstrate that salivary cortisol is a useful measure of stress
      response that can be used to evaluate intervention effectiveness.

PMID- 19171297
TI  - Research access to adolescents and young adults.
AB  - Gaining research access to adolescents and young adults is not straightforward
      and involves layers of negotiation and administration. Experiences of accessing
      adolescents and young adults aged 13-21 years are described in this article.
      Issues raised for consideration are: identifying clinical gatekeepers; seeking
      ethical approval; making direct contact with adolescents and young adults
      (hereafter referred to as young people); and dealing with parents as gatekeepers.
      Refusal rates, participation rates, and reasons are also considered. The issues
      raised provide practical insights that may be helpful to other researchers aiming
      to access adolescents and young adults.

PMID- 19171298
TI  - Does the number of raters influence the pressure ulcer prevalence rate?
AB  - We analyzed data from pressure ulcer prevalence studies conducted in nursing
      homes between 2004 and 2006 concerning differences in the observed pressure ulcer
      prevalence rates while looking into the number of nurses conducting skin
      inspections (one or two). Results of the analysis revealed that the number of
      raters did not influence the observed pressure ulcer prevalence rate. Adequate
      preparation and training of ward nurses for data collection seem to be sufficient
      to achieve reliable data.

PMID- 19171299
TI  - Fulbright Scholar opportunities for global health and women's health care in
      HIV/AIDS in sub-Saharan Africa.
AB  - This article addresses global health opportunities related to HIV/AIDS and
      women's health care in sub-Saharan Africa through Fulbright Scholar and Fulbright
      Student Awards. Although many universities offer a gateway to the J. William
      Fulbright awards, some disciplines and areas of specialization, including nursing
      and women's health, have had fewer scholars or students as recipients of these
      awards. Resource-limited countries, including the countries of sub-Saharan
      Africa, offer rich opportunities for cross-cultural exchange and advancement of
      global health. Amidst the context of the shortage of health care workers, the
      increasing prevalence of HIV/AIDS and other infectious and chronic diseases in
      sub-Saharan Africa, and the challenges of public health, this article addresses
      an example of partnerships in global nursing that can be developed through the
      Fulbright programs.

PMID- 19171300
TI  - Biobased performance bioplastic: Mirel.

PMID- 19171301
TI  - Photocrosslinking and click chemistry enable the specific detection of proteins
      interacting with phospholipids at the membrane interface.
AB  - New lipid analogs mimicking the abundant membrane phospholipid
      phosphatidylcholine were developed to photocrosslink proteins interacting with
      phospholipid headgroups at the membrane interface. In addition to either a
      phenylazide or benzophenone photoactivatable moiety attached to the headgroup,
      the lipid analogs contained azides attached as baits to the acyl chains. After
      photocrosslinking in situ in the biomembrane, these baits were used for the
      attachment of a fluorescent tetramethylrhodamine-alkyne conjugate or a biotin
      alkyne conjugate using click chemistry, allowing for the selective detection and
      purification of crosslink products, respectively. Proteins crosslinked to the
      lipid analogs in inner mitochondrial membranes from Saccharomyces cerevisiae were
      detected and subsequently identified by mass spectrometry. Established
      interaction partners of phosphatidylcholine were found, as well as known integral
      and peripheral inner membrane proteins, and proteins that were not previously
      considered mitochondrial inner membrane proteins.

PMID- 19171302
TI  - Involvement of GSK-3 in regulation of murine embryonic stem cell self-renewal
      revealed by a series of bisindolylmaleimides.
AB  - The ability to propagate embryonic stem cells (ESCs) while maintaining their
      pluripotency is critical if their potential use in regenerative medicine is to be
      realized. The mechanisms controlling ESC self-renewal are under intense
      investigation, and glycogen synthase kinase 3 (GSK-3) has been implicated in
      regulating both self-renewal and differentiation. To clarify its role in ESCs we
      have used chemical genetics. We synthesized a series of bisindolylmaleimides, a
      subset of which inhibit GSK-3 in murine ESCs and robustly enhance self-renewal in
      the presence of leukemia inhibitory factor (LIF) and serum, but not in the
      absence of LIF. Importantly, these molecules appear selective for GSK-3 and do
      not perturb other signaling pathways regulating self-renewal. Our study clarifies
      the functional importance of GSK-3 in regulation of ESC self-renewal and provides
      tools for investigating its role further.

PMID- 19171303
TI  - Engineering a function into a glycosyltransferase.
AB  - As glycosyltransferases found in nature often show distinct substrate
      specificity, glycosyltransferase engineering is an important research field. In
      this work, we were able to introduce an activity into a glycosyltransferase
      involved in natural product (landomycin E) biosynthesis. This was achieved by
      recognizing hot spot amino acids in glycosyltransferases which are strongly
      involved in determining substrate specificity.

PMID- 19171304
TI  - Novel fluorescent glycan microarray strategy reveals ligands for galectins.
AB  - Galectin-1 (Gal-1) and galectin-3 (Gal-3) are widely expressed galectins with
      immunoregulatory functions in animals. To explore their glycan specificity, we
      developed microarrays of naturally occurring glycans using a bifunctional
      fluorescent linker, 2-amino-N-(2-aminoethyl)-benzamide (AEAB), directly
      conjugated through its arylamine group by reductive amination to free glycans to
      form glycan-AEABs (GAEABs). Glycans from natural sources were used to prepare
      over 200 GAEABs, which were purified by multidimensional high-pressure liquid
      chromatography and covalently immobilized onto N-hydroxysuccinimide-activated
      glass slides via their free alkylamine. Fluorescence-based screening demonstrated
      that Gal-1 recognizes a wide variety of complex N-glycans, whereas Gal-3
      primarily recognizes poly-N-acetyllactosamine-containing glycans independent of N
      glycan presentation. GAEABs provide a general solution to glycan microarray
      preparation from natural sources for defining the specificity of glycan-binding
      proteins.

PMID- 19171305
TI  - Visualization of Src activity at different compartments of the plasma membrane by
      FRET imaging.
AB  - Membrane compartments function as segregated signaling platforms for different
      cellular functions. It is not clear how Src is regulated at different membrane
      compartments. To visualize local Src activity in live cells, a FRET-based Src
      biosensor was targeted in or outside of lipid rafts at the plasma membrane, via
      acylation or prenylation modifications on targeting tags either directly fused to
      the biosensor or coupled to the biosensor through an inducible heterodimerization
      system. In response to growth factors and pervanadate, the induction of Src
      activity in rafts was slower and weaker, dependent on actin and possibly its
      mediated transportation of Src from perinuclear regions to the plasma membrane.
      In contrast, the induction of Src activity in nonrafts was faster and stronger,
      dependent on microtubules. Hence, Src activity is differentially regulated via
      cytoskeleton at different membrane compartments.

PMID- 19171306
TI  - Screening and characterization of surface-tethered cationic peptides for
      antimicrobial activity.
AB  - There is an urgent need to coat the surfaces of medical devices, including
      implants, with antimicrobial agents to reduce the risk of infection. A peptide
      array technology was modified to permit the screening of short peptides for
      antimicrobial activity while tethered to a surface. Cellulose-amino-hydroxypropyl
      ether (CAPE) linker chemistry was used to synthesize, on a cellulose support,
      peptides that remained covalently bound during biological assays. Among 122
      tested sequences, the best surface-tethered 9-, 12-, and 13-mer peptides were
      found to be highly antimicrobial against bacteria and fungi, as confirmed using
      alternative surface materials and coupling strategies as well as coupling through
      the C and N termini of the peptides. Structure-activity modeling of the
      structural features determining the activity of tethered peptides indicated that
      the extent and positioning of positive charges and hydrophobic residues were
      influential in determining activity.

PMID- 19171307
TI  - Unusual chemistry in the biosynthesis of the antibiotic chondrochlorens.
AB  - The antibiotic chondrochlorens A and B from the myxobacterium Chondromyces
      crocatus Cm c5 incorporate several unusual structural features, notable among
      them a shared chloro-hydroxy-styryl functionality and the ethoxy group of
      chondrochloren B. Our analysis of the chondrochloren gene cluster by targeted
      gene inactivation coupled with assays in vitro has shed significant light on the
      biosynthesis of these metabolites. Chlorination of tyrosine occurs early in the
      pathway, likely on a peptidyl carrier protein-bound intermediate, whereas
      decarboxylation to the styryl moiety appears to be accomplished by an
      unprecedented oxidative decarboxylase. We also show that the chondrochloren B
      ethoxy group arises from initial incorporation by the polyketide synthase of
      hydroxy malonate as an extender unit, methylation in cis by an O
      methyltransferase, followed by a second methylation. This report therefore
      constitutes a direct demonstration of the involvement of a radical S
      adenosylmethionine methylase in bacterial secondary metabolism.

PMID- 19171308
TI  - Mycolic acids constitute a scaffold for mycobacterial lipid antigens stimulating
      CD1-restricted T cells.
AB  - CD1-restricted lipid-specific T lymphocytes are primed during infection with
      Mycobacterium tuberculosis, the causative agent of tuberculosis. Here we describe
      the antigenicity of glycerol monomycolate (GroMM), which stimulates CD1b
      restricted CD4(+) T cell clones. Chemical characterization of this antigen showed
      that it exists as two stereoisomers, one synthetic isomer being more stimulatory
      than the other. The hydroxyl groups of glycerol and the mycolic acid length are
      critical for triggering the T cell responses. GroMM was presented by M.
      tuberculosis-infected dendritic cells, demonstrating that the antigen is
      available for presentation during natural infection. Ex vivo experiments showed
      that GroMM stimulated T cells from vaccinated or latently infected healthy donors
      but not cells from patients with active tuberculosis, suggesting that GroMM
      specific T cells are primed during infection and their detection correlates with
      lack of clinical active disease.

PMID- 19171309
TI  - A chemical genomic approach identifies matrix metalloproteinases as playing an
      essential and specific role in Xenopus melanophore migration.
AB  - To dissect the function of matrix metalloproteinases (MMPs) involved in cellular
      migration in vivo, we undertook both a forward chemical genomic screen and a
      functional approach to discover modulators of melanophore (pigment cell)
      migration in Xenopus laevis. We identified the 8-quinolinol derivative NSC 84093
      as affecting melanophore migration in the developing embryo and have shown it to
      act as a MMP inhibitor. Potential targets of NSC 84093 investigated include MMP
      14 and MMP-2. MMP-14 is expressed in migrating neural crest cells from which
      melanophores are derived. MMP-2 is expressed at the relevant time of development
      and in a pattern that suggests it contributes to melanophore migration.
      Morpholino-mediated knockdown of both MMPs demonstrates they play a key role in
      melanophore migration and partially phenocopy the effect of NSC 84093.

PMID- 19171310
TI  - The contributions of weight problem perception, BMI, gender, mood, and smoking
      status to binge eating among college students.
AB  - College student participants (N=1063; 77.8% response rate) completed a web-based
      survey assessing demographics, depression, anxiety, body image, cigarette
      smoking, and weight history. Among overweight participants, 42.6% of those who
      believed they were overweight admitted to binge eating, while only 30.1% who did
      not feel overweight did so (p<.05). Among non-overweight participants, 43.2% of
      those who believed they were overweight admitted to binge eating, while only
      32.9% of those who did not feel overweight did so (p<.05). Weight Problem
      Perception (WPP) mediated the contribution of BMI on binge eating outcomes, and
      WPP contributed significantly to the prediction of binge eating, beyond the risk
      conferred by established correlates of binge eating (e.g., gender, mood, and
      cigarette smoking). Results suggest that when assessing risk for binge eating, a
      one-question assessment of whether or not an individual believes s/he is
      overweight has significant predictive power. Findings are consistent with
      literature on the importance of the "fat self-schema" [Stein, K.F., & Corte, C.
      (2007). Identity impairment and the eating disorders: Content and organization of
      the self-concept in women with anorexia nervosa and bulimia nervosa. European
      Eating Disorders Review, 15 (1), 58-69] in disordered eating and theory
      implicating identity in the maintenance of addictive behavior [West, R.W. (2006).
      Theory of Addiction. Malden, MA: Blackwell Publishing, Inc.].

PMID- 19171311
TI  - A consideration of developmental egocentrism in anorexia nervosa.
AB  - Recent research has suggested that normal adolescent processes are important in
      understanding psychosis, and that young adult individuals with psychosis are
      often struggling to develop an individual and autonomous self (the "fundamental
      task" of adolescence). The current paper explores the utility of considering
      normative adolescent developmental processes in understanding anorexia nervosa.
      Data were collected from 31 female young-adults with symptoms of anorexia
      nervosa, 26 female comparison young-adults and 71 female adolescents on measures
      of adolescent egocentrism. A one-way ANOVA indicated that individuals with
      symptoms of anorexia nervosa scored more highly than both their peers and the
      adolescents on several dimensions of egocentric developmental beliefs.
      Correlations also showed that egocentrism was positively associated with eating
      concern in participants with symptoms of anorexia. The results suggest that young
      adult women with symptoms of anorexia nervosa tended to feel physically
      invulnerable while also feeling both psychologically vulnerable to others and
      special or different. Together with the finding of excessive self-consciousness,
      this supports a notion that they may be experiencing exaggerated versions of
      normal self-developmental phenomena. Clinically, offering alternative ways of
      feeling unique other than dieting may be important in therapeutic approaches to
      anorexia nervosa. Similarly, strategies aimed at normalisation, such as
      facilitating healthy attachment to peers, may be useful for individuals with
      anorexia nervosa.

PMID- 19171312
TI  - Body attitudes in patients with eating disorders at presentation and completion
      of intensive outpatient day treatment.
AB  - Due to the importance of the distorted body experience in eating disorder
      diagnosis and treatment, we wanted to explore body attitudes of patients with
      eating disorders before and after 5 months of intensive specialized outpatient
      day treatment. We assessed 193 patients diagnosed with Anorexia Nervosa (AN),
      Bulimia Nervosa (BN) and Eating Disorder Not Otherwise Specified (EDNOS) using
      the Body Attitude Test (BAT), Body Mass Index (BMI), Eating Disorder Evaluation
      Scale (EDES) and Symptom Checklist 90 (SCL-90). Eating disorder subtypes differed
      in BMI, total body attitudes and negative appreciation of body size at intake,
      but not at termination of treatment. Following treatment, all patient groups
      reported large improvements in eating disorder pathology and all but the AN
      Restrictive (AN-R) group, reported large improvements in overall psychological
      functioning. The AN patients demonstrated significant improvement in BMI, however
      the Anorexia Nervosa purging (AN-P) and Anorexia Nervosa restrictive (AN-R)
      subtypes differed in their changes in body attitudes. AN-R patients indicated no
      significant improvement in body attitudes. AN-P patients improved in total body
      attitudes, except one subscale. Patients with Bulimia Nervosa non-purging (BN-NP)
      subtype, Bulimia Nervosa purging (BN-P) subtype and EDNOS demonstrated similar
      improvements in total body attitudes (BAT). Body attitudes provide important
      insights into differences between eating disorder diagnostic categories and their
      treatment responsiveness.

PMID- 19171313
TI  - Binge eating in adolescents: its relation to behavioural problems and family-meal
      patterns.
AB  - The aim of the study was to explore the relationship between binge eating,
      behavioural problems and family-meal patterns in a sample of adolescents. Two
      hundred and fifty-nine adolescents from a public secondary school completed the
      Bulimic Investigatory test, Edinburgh (BITE) [Henderson, M., & Freeman, C. P.
      (1987). A self-rating scale for bulimia. The "BITE". British Journal of
      Psychiatry, 150, 18-24.] and the Youth Self-Report (YSR) [Achenbach, T. M.
      (1991). Manual for the Youth Self-Report and 1991 profile. Burlington, VT:
      University of Vermont.], as well as 13 additional questions regarding the eating
      episodes and family-meal patterns. The results show that binge eating is a
      frequent behaviour in adolescence with 33.2% of the sample reporting binge eating
      at least once in the last six months. The adolescents who reported binge eating
      had higher scores on most of the YSR first-order factors compared to those who do
      not engage in this behaviour. No differences were found in family meal patterns.
      Questions regarding the binge-eating episodes were also analysed making
      comparisons by age and gender.

PMID- 19171314
TI  - Exercise and energy intake in overweight, sedentary individuals.
AB  - Exercise expends energy, but without dietary intervention, exercise does not
      appear to produce substantial weight loss. The present study examined whether
      overweight, sedentary individuals increase their energy intake after moderate
      intensity exercise, particularly in the presence of negative mood. A repeated
      measures design was used where overweight, sedentary individuals (N=65)
      completed, in counterbalanced order, two conditions: 3 min of exercise (Active)
      and 3 min of sedentary activity (Sedentary) during one session. Snack foods were
      presented 10 min after each activity. Mixed-effects regression modeling revealed
      no significant effect of Active versus Sedentary condition on energy intake.
      However, moderational analyses revealed that change in negative mood interacted
      with condition to predict energy intake, such that participants who reported
      increased negative mood during exercise consumed more calories in the Active
      compared to the Sedentary condition. That a short bout of exercise resulted in
      mood deterioration and increased energy intake for some overweight, sedentary
      individuals is concerning. Further research examining behavioral and
      physiological mechanisms of mood deterioration and caloric overcompensation
      following exercise in overweight, sedentary individuals is warranted.

PMID- 19171316
TI  - The relationship between restrained eating, pleasure associated with eating, and
      well-being re-visited.
AB  - Appleton and McGowan [Appleton, K. M. & McGowan, L. (2006). The relationship
      between restrained eating and poor psychological health is moderated by pleasure
      normally associated with eating. Eating Behaviors, 7, 342-347.] reported that
      pleasure associated with eating is an important moderator of the relationship
      between restrained eating and well-being. Using questionnaires, the current study
      re-visited this issue in order to determine the exact conformation of this
      interaction between pleasure and restraint and how it might predict well-being. A
      significant relationship was found between restraint and well-being--higher
      restraint scores were predictive of lower self-clarity, lower life satisfaction,
      and higher neuroticism. Furthermore, pleasure was an important moderator of this
      relationship for both self-clarity and neuroticism. Conditional slopes analyses
      revealed that individuals who were both high on pleasure associated with eating
      and high on restraint showed the lowest self-clarity and the highest neuroticism
      scores, while the opposite pattern was found for those high on pleasure but low
      on restraint. This study confirms that pleasure associated with eating is an
      important moderator of the relationship between restrained eating and well-being.

PMID- 19171317
TI  - Group work with female survivors of childhood sexual abuse: evidence of poorer
      outcomes among those with eating disorders.
AB  - OBJECTIVE: This study explored levels of depression and self-esteem after
      childhood sexual abuse (CSA) group treatment for survivors with and without
      histories of eating disorders (ED). METHODS: Fifty adult female survivors
      completed a 15-week CSA group treatment program and were assessed at intake, pre
      group treatment, discharge, and six months follow-up using the Beck Depression
      Inventory, the Generalized Contentment Scale and the Index of Self-Esteem. They
      were also asked to report on their CSA histories and comorbid psychiatric issues
      including histories of ED. RESULTS: Survivors with reported histories of anorexia
      nervosa or bulimia nervosa were significantly more depressed (minimum p<.05) and
      tended to have significantly less self-esteem (minimum p<.10) at discharge and
      six-month follow-up than those without ED. The size of these effects suggested
      their potential clinical significance as well. Seven to nine of every ten clients
      with histories of ED were more depressed and had lower self-esteem than the
      typical client without ED at discharge and at six-month follow-up. CONCLUSION:
      The findings suggest that CSA treatment programs should assess survivors for ED
      as they might benefit from a more specialized focus on their emotional responses
      to the abuse.

PMID- 19171315
TI  - Acute tryptophan depletion and sweet food consumption by overweight adults.
AB  - Serotonergic involvement has been implicated in preferential consumption of treat
      foods. We tested the effect of acute tryptophan depletion (ATD) on food
      consumption by overweight and lean adults with and without a history of recurrent
      major depressive disorder (MDD). ATD and taste-matched placebo challenges were
      administered double-blind in counter-balanced order. Participants were classified
      as lean (n=36) or overweight (n=19) on the basis of body mass index (BMI). Total
      calorie, carbohydrate, protein, and sweet food consumption were assessed via a
      test meal 8-h following ATD. Four food items of comparable palatability were
      offered as a part of the test: two sweet (one carbohydrate-rich, and one protein
      rich) and two non-sweet (one carbohydrate-rich, and one protein-rich). As
      compared to the placebo challenge, ATD significantly increased sweet calorie
      intake among overweight participants and increased their propensity to consume
      sweet food first before any other type of food. Lean participants' sweet calorie
      intake and food preference were unaffected by ATD. Findings suggest serotonergic
      involvement in the sweet food consumption by overweight individuals.

PMID- 19171318
TI  - Never-smokers with a positive family smoking history are more likely to be
      overweight or obese than never-smokers with a negative family smoking history.
AB  - To shed light on the complex relationship between smoking and body weight, we
      used never-smokers stratified on family smoking history to model the effects of a
      diathesis for smoking on body weight without the potential confound of metabolic
      changes or decreased physical activity caused by chronic tobacco smoke exposure.
      Participants were 100 family history negative never-smokers (FH-; 2 never-smoking
      parents) and 71 family history positive never-smokers (FH+; 2 ever-smoking
      parents). Controlling for significant group differences in race and age, BMI was
      significantly higher in FH+ (26.7+/-.6) than in FH- (24.5+/-.4; F=10.351 p<.01).
      Further analysis using logistic regression showed that FH+ were 2.7 times as
      likely to be overweight/obese (BMI > or = 25; 95% C.I. 1.398-5.351; p<.01). FH+
      scored significantly higher on the Dieting and Bingeing Severity Scale than FH-
      and were significantly more likely to score in the severe or at-risk range. FH+
      drank significantly more alcohol than FH-; they scored significantly higher on
      the CAGE and on the Michigan Alcohol Screening Test. Our analyses provide support
      for the role of inherited and/or environmentally-driven tendencies towards
      disinhibited eating and/or risky behaviors in general in the observed differences
      in BMI. No group differences in BMI or likelihood of being overweight/obese
      emerged based on prenatal exposure to nicotine in FH+ smokers, although our
      sample was too small to rule out an association. Further research in larger
      samples, using more complex statistical models, will be needed to disentangle
      these issues and identify causal pathways.

PMID- 19171320
TI  - Cigarette smoking is associated with body shape concerns and bulimia symptoms
      among young adult females.
AB  - Elevated rates of cigarette smoking have been reported among individuals with
      Bulimia Nervosa. However, little is known about eating disorder symptoms within
      non-clinical samples of smokers. The purpose of the present study was to compare
      the eating disorder symptoms of young adult female smokers (n=184) and non
      smokers (n=56), to determine whether smokers were more likely to endorse bulimic
      symptoms and report greater body shape concern than non-smokers. Analyses
      indicated that smokers scored significantly higher than non-smokers on the Body
      Shape Questionnaire, p=.03, and the Bulimia Test-Revised, p=.006. In addition, a
      higher proportion of smokers than non-smokers scored > or = 85 on the Bulimia
      Test-Revised, p=.05, suggesting the possibility that Bulimia Nervosa diagnoses
      were more prevalent among smokers. No differences were found between smokers and
      non-smokers on other measures of eating behavior. Overall, findings suggest that
      smoking is specifically associated with symptoms of Bulimia Nervosa and body
      shape concern among young adult females.

PMID- 19171319
TI  - Short-term weight gain by menstrual phase following smoking cessation in women.
AB  - Prevention of early weight gain may be critical to avoid relapse among women with
      a fear of weight gain. Menstrual phase has physiological fluctuation of fluid
      resulting in short-term weight gain, suggesting menstrual phase of smoking
      cessation may impact short-term weight gain. This study examined the effect of
      smoking abstinence and menstrual cycle on short-term weight gain. Women were
      randomized to quit smoking during the follicular or luteal phase of their cycle
      and followed for four weeks. Weight, among other measures, was recorded at five
      post-quit date visits (days 2, 5, 9, 12 and week 4). Participants (n=152) were
      grouped based on randomized quit phase and smoking status after assigned quit
      date: 1) follicular (F), quit < 24 h, 2) F, quit > or = five days, 3) luteal (L),
      quit < 24 h, and 4) L, quit > or = five days. Participants who quit smoking
      experienced significantly more weight gain than those who quit for less than 24
      h. There were no significant increases in short-term weight gain based on
      menstrual cycle phase during attempted smoking cessation.

PMID- 19171321
TI  - Psychometric properties of self-monitoring of eating disorder urges among
      treatment seeking women: ecological momentary assessment using a daily diary
      method.
AB  - OBJECTIVES: The psychometric properties of an ecological momentary assessment
      (EMA) method used to evaluate eating disorder (ED) urges were examined. METHODS:
      Participants, 139 women who sought treatment for an ED, completed a daily diary
      measuring ED urges after each meal for a three week period at the start of
      treatment, and a measure of ED attitudes and behaviors pre- and post-treatment.
      RESULTS: The construct validity of this method was indicated by a two factor
      solution representing binge eating urges and ED compensatory behavior urges, and
      by significant differences between ED diagnostic groups on ED urge type.
      Correlations of ED urges early in therapy with outcomes provided evidence for
      predictive validity. Correlations at pre-treatment between ED urges and ED
      attitudes and behaviors supported criterion validity. EMA of ED urges showed good
      retest stability. CONCLUSIONS: EMA of ED urges is a valid and reliable approach
      that is associated with ED symptom severity, and predictive of treatment outcome.

PMID- 19171322
TI  - Clinical and psychometric validation of an extended version of the Testable
      Assumptions Questionnaire (TAQ-ED-R).
AB  - OBJECTIVE: Testable dysfunctional assumptions are a central aspect of the
      cognitive profile of patients with eating disorders. These are conditional
      beliefs that can be challenged directly using techniques such as behavioural
      experiments and surveys. Recent research has suggested that such assumptions fall
      into three classes (assumptions about one's body, one's feelings and the world),
      but the emerging scale had only relatively few items. The present study examines
      the clinical and psychometric utility of an extended version of that scale--the
      Testable Assumptions Questionnaire-Eating Disorders-Revised (TAQ-ED-R). METHOD:
      The TAQ-ED-R and the Eating Disorders Examination-Questionnaire (EDE-Q) were
      administered to 200 women--72 with eating disorders, and 128 with no eating
      disorder. Differences between anorexic, bulimic and non-clinical women were
      examined, and associations with EDE-Q scores were tested. RESULTS: The three
      subscales had adequate to good internal consistency across all three samples. The
      two clinical groups reported relatively high levels of testable assumptions, but
      there was no difference between the anorexic and bulimic women on the overall
      scale. Although all three forms of testable assumption were associated with
      levels of eating pathology, assumptions relating to one's body were the key
      correlate. DISCUSSION: The TAQ-ED-R is a clinically useful measure of
      dysfunctional assumptions that can be tested with the help of behavioural
      experiments and surveys. It will be important to test the predictive validity of
      the new measure, as well as its capacity to drive treatment for comorbid states,
      such as alexithymia and social anxiety.

PMID- 19171323
TI  - Osteoporosis health beliefs and knowledge in college students: the role of
      dietary restraint.
AB  - This study investigated the relationship between dietary restraint (DR) and
      osteoporosis-related knowledge and beliefs in college women and men. A total of
      517 university students completed measures of osteoporosis knowledge, perceived
      susceptibility to and severity of osteoporosis, barriers to and benefits of
      calcium and exercise, health motivation, exercise and calcium self-efficacy, and
      DR. Two MANOVAs were conducted to examine differences between high and low
      dietary restrainers on osteoporosis beliefs and knowledge. For women, HR scored
      higher on perceived susceptibility to, and severity of, osteoporosis, calcium
      barriers, and health motivation; for men, HR scored lower on exercise benefits.
      These results suggest that DR may be related to osteoporosis beliefs and
      knowledge differently for men and women.

PMID- 19171324
TI  - Men, muscles, and mood: the relationship between self-concept, dysphoria, and
      body image disturbances.
AB  - Beginning in the early 1990s investigations into the body image concerns of men
      have increased, and this study adds to extant research by examining correlates of
      more general body dissatisfaction (BD) and symptoms of muscle dysmorphia (MD) in
      particular. Three hundred four undergraduate men completed a broad-based symptom
      inventory, a self-concept questionnaire, and an instrument that assessed
      problematic body image, eating, and exercise patterns as well as specific
      symptoms of MD. Multiple regression analyses suggest that lower ratings of
      overall self-concept and higher levels of depression, anxiety, and interpersonal
      sensitivity are predictive of body image concerns in men. Furthermore, these
      variables accounted for almost twice the variance in general BD than they did for
      specific symptoms of MD. In addition, anorexic and bulimic behaviors, obsessive
      compulsive symptoms, and risk factors for interpersonal problems were also
      associated with symptoms of MD, even when BD was controlled.

PMID- 19171325
TI  - Weight parameters and pathological eating as predictors of obesity treatment
      outcome in children and adolescents.
AB  - OBJECTIVE: The current study investigated weight parameters and pathological
      eating as predictors of treatment outcome in obese youngsters. METHOD: Obese
      youngsters (N=132) were examined before participating in an obesity treatment
      program. Weight loss was measured during and at the end of treatment. RESULTS:
      Baseline adjusted BMI, restrained eating style and weight loss after 4 months of
      treatment positively predicted weight loss at the end, whereas larger weight loss
      after 1 month of treatment predicted less total weight loss. Lower baseline
      adjusted BMI was associated with more drop-out whereas subjective binge eating
      was positively related to program completion. CONCLUSION: Specific weight and
      eating pathology parameters affected positive as well as negative obesity
      treatment outcome. Identifying more pre-treatment predictors for drop-out can
      ameliorate our treatment approach.

PMID- 19171326
TI  - A connectionist model of a continuous developmental transition in the balance
      scale task.
AB  - A connectionist model of the balance scale task is presented which exhibits
      developmental transitions between 'Rule I' and 'Rule II' behavior [Siegler, R. S.
      (1976). Three aspects of cognitive development. Cognitive Psychology,8, 481-520.]
      as well as the 'catastrophe flags' seen in data from Jansen and van der Maas
      [Jansen, B. R. J., & van der Maas, H. L. J. (2001). Evidence for the phase
      transition from Rule I to Rule II on the balance scale task. Developmental
      Review, 21, 450-494]. The model extends a connectionist model of this task
      [McClelland, J. L. (1989). Parallel distributed processing: Implications for
      cognition and development. In R. G. M. Morris (Ed.), Parallel distributed
      processing: Implications for psychology and neurobiology (pp. 8-45). Oxford:
      Clarendon Press] by introducing intrinsic variability into processing and by
      allowing the network to adapt during testing in response to its own outputs. The
      simulations direct attention to several aspects of the experimental data
      indicating that children generally show gradual change in sensitivity to the
      distance dimension on the balance scale. While a few children show larger changes
      than are characteristic of the model, its ability to account for nearly all of
      the data using continuous processes is consistent with the view that the
      transition from Rule I to Rule II behavior is typically continuous rather than
      discrete in nature.

PMID- 19171327
TI  - Commentary on the levels of pesticide exposure in general and rural population
      based on the article titled "A comparison of infant hair, cord blood and meconium
      analysis to detect fetal exposure to environmental pesticides" by Ostrea et al.
      [Environ. Res. 106 (2008) 277-283].

PMID- 19171328
TI  - Factors controlling physico-chemical characteristics in the coastal waters off
      Mangalore--a multivariate approach.
AB  - Water quality parameters (temperature, pH, salinity, DO, BOD, suspended solids,
      nutrients, PHc, phenols, trace metals--Pb, Cd and Hg, chlorophyll-a (chl-a) and
      phaeopigments) and the sediment quality parameters (total phosphorous, total
      nitrogen, organic carbon and trace metals) were analysed from samples collected
      at 15 stations along 3 transects off Karnataka coast (Mangalore harbour in the
      south to Suratkal in the north), west coast of India during 2007. The analyses
      showed high ammonia off Suratkal, high nitrite (NO(2)-N) and nitrate (NO(3)-N) in
      the nearshore waters off Kulai and high nitrite (NO(2)-N) and ammonia (NH(3)-N)
      in the harbour area. Similarly, high petroleum hydrocarbon (PHc) values were
      observed near the harbour, while phenols remained high in the nearshore waters of
      Kulai and Suratkal. Significantly, high concentrations of cadmium and mercury
      with respect to the earlier studies were observed off Kulai and harbour regions,
      respectively. R-mode varimax factor analyses were applied separately to surface
      and bottom water data sets due to existing stratification in the water column
      caused by riverine inflow and to sediment data. This helped to understand the
      interrelationships between the variables and to identify probable source
      components for explaining the environmental status of the area. Six factors (each
      for surface and bottom waters) were found responsible for variance (86.9% in
      surface and 82.4% in bottom) in the coastal waters between Mangalore and
      Suratkal. In sediments, 4 factors explained 86.8% of the observed total variance.
      The variances indicated addition of nutrients and suspended solids to the coastal
      waters due to weathering and riverine transport and are categorized as natural
      sources. The observed contamination of coastal waters indicated anthropogenic
      inputs of Cd and phenol from industrial effluent sources at Kulai and Suratkal,
      ammonia from wastewater discharges off Kulai and harbour, PHc and Hg from boat
      traffic and harbour activities of New Mangalore harbour. However, the strong
      seasonal currents and the seasonal winds keep the coastal waters well mixed and
      aerated, which help to disperse the contaminants, without significantly affecting
      chlorophyll-a concentrations. The interrelationship between the stations as shown
      by cluster analyses and depicted in dendograms, categorize the contamination
      levels sector-wise.

PMID- 19171329
TI  - Creation of a neovagina in Rokitansky patients with a pelvic kidney: comparison
      of long-term results of the modified Vecchietti and McIndoe techniques.
AB  - OBJECTIVE: To evaluate perioperative data and long-term results of Rokitansky
      patients with a pelvic kidney that underwent the McIndoe and modified Vecchietti
      procedures. DESIGN: Retrospective descriptive study. SETTING: A tertiary referral
      center for the study and treatment of Rokitansky syndrome. PATIENT(S): Eleven
      patients with Rokitansky syndrome. INTERVENTION(S): Two and nine patients,
      respectively, underwent the McIndoe and Vecchietti modified techniques. MAIN
      OUTCOME MEASURE(S): Anatomic success was defined as a neovagina > or =6 cm long
      allowing easy introduction of two fingers within 6 months postoperatively.
      Functional success was considered achieved when the patient reported satisfactory
      sexual intercourse starting from 6 months postoperatively. RESULT(S): Surgery was
      performed with no complications in all 11 patients. The mean duration of surgery
      was 190 +/- 14.1 minutes in the first group and 32 +/- 6.4 minutes in the second
      group. At 14 years of follow-up, both patients who underwent McIndoe vaginoplasty
      had a mean +/- SD length and width of 8.2 +/- 0.4 cm and 5 cm and negative
      Schiller's test 24 months postoperatively. At 4 years of follow-up, eight out of
      the nine patients who underwent the Vecchietti procedure (89%) had a mean +/- SD
      length and width of the neovagina of 7.4 +/- 0.6 cm and 4.2 +/- 0.5 cm and iodine
      positive vaginal-type epithelium coating 100% of the neovagina 24 months
      postoperatively. CONCLUSION(S): While appearing to be safe, effective, and with
      optimal functional results, the modified Vecchietti approach also seems to yield
      good anatomical and aesthetic results along with shorter surgical and
      hospitalization times.

PMID- 19171330
TI  - Mutational analysis of the WNT gene family in women with Mayer-Rokitansky-Kuster
      Hauser syndrome.
AB  - The aim of this study is to determine if Mullerian agenesis has a genetic basis
      linked to the WNT genes. Genomic DNA analyses for mutations in the coding
      sequences of four members of this family in a series of 11 women with Mayer
      Rokitansky-Kuster-Hauser syndrome found four variants in the coding sequence of
      these genes, but causal mutations were not observed. This supports the hypothesis
      that mutations in the coding sequence of WNT4, WNT5A, WNT7A, and WNT9B are not
      responsible for the Mayer-Rokitansky-Kuster-Hauser syndrome.

PMID- 19171331
TI  - Health of children born after ovulation induction.
AB  - OBJECTIVE: To study the health of children born after ovulation induction (OI).
      DESIGN: Nationwide register-based study. SETTING: The OI children were followed
      up to the age of 4 years and compared with other children. PATIENT(S): The OI
      children (N = 4,467). Two control groups: all other children (excluding children
      born after IVF, N = 190,398) and a random sample of those children (n = 26,877).
      INTERVENTION(S): Ovulation induction treatment in ordinary practice. MAIN OUTCOME
      MEASURE(S): Mortality rates and adjusted odds ratios for perinatal outcomes,
      hospitalizations, health-related benefits, and long-term medication use.
      RESULT(S): A total of 12% of OI and 2% of control children were multiples. Even
      after stratifying for multiplicity and adjusting for the available confounding
      factors (region, smoking, maternal age, socioeconomic position, and parity for
      perinatal health and mother's socioeconomic position for other indicators), most
      indicators showed worse health among OI children compared with control children.
      The OI children had poorer perinatal health and more episodes of long
      hospitalization than the control children. Singleton OI children had more long
      term illnesses in childhood, as measured by child disability allowance, long-term
      medication use, and hospital care episodes. CONCLUSION(S): Either OI treatment or
      the reasons for the treatment increase the risk of health problems in early
      childhood.

PMID- 19171332
TI  - The effect of serum and intrafollicular insulin resistance parameters and
      homocysteine levels of nonobese, nonhyperandrogenemic polycystic ovary syndrome
      patients on in vitro fertilization outcome.
AB  - OBJECTIVE: To investigate the serum and follicular fluid concentrations of
      insulin resistance parameters and homocysteine and their effect on IVF outcome in
      nonobese, nonhyperandrogenemic polycystic ovary syndrome patients. DESIGN:
      Prospective study. SETTING: Department of Infertility of Dr. Zekai Tahir Burak
      Women's Health Research and Education Hospital. PATIENT(S): Ninty-seven women
      underwent IVF. INTERVENTION(S): Subjects were categorized according to IVF
      indications: group 1 with polycystic ovary syndrome (PCOS), group 2 with
      subfertile male partners, group 3 with unexplained infertiliy. Serum and
      follicular fluid parameters from the first follicle on the day of oocyte
      retrieval were analyzed. MAIN OUTCOME MEASURE(S): Serum and follicular fluid
      insulin resistance parameters, homocysteine, sex hormone levels, and laboratory
      and clinical IVF outcome were studied. RESULT(S): Serum insulin, homeostasis
      model assessment estimate of insulin resistance (HOMA-IR), and homocysteine
      levels were significantly higher in subjects having PCOS. However, these
      significant differences in serum insulin resistance and homocysteine levels were
      not seen in the follicular microenvironment. There were no differences in
      clinical pregnancy rates between study groups. CONCLUSION(S): Despite elevated
      serum insulin, HOMA-IR, and homocysteine levels, and their effects on oocyte
      numbers and maturation in PCOS patients, there were no differences in follicular
      parameters and clinical pregnancy rates between hyperinsulinemic and
      hyperhomocysteinemic PCOS patients and the other two groups.

PMID- 19171333
TI  - Does endometrial integrin expression in endometriosis patients predict enhanced
      in vitro fertilization cycle outcomes after prolonged GnRH agonist therapy?
AB  - OBJECTIVE: To determine whether endometrial expression of the integrin
      alpha(v)beta(3) vitronectin can predict which endometriosis patient subgroup will
      benefit from pre-IVF cycle prolonged GnRH agonist (GnRHa) therapy. DESIGN:
      Prospective randomized institutional review board approved pilot trial. SETTING:
      Private assisted reproductive technology program. PATIENT(S): IVF candidates with
      regular menses, surgically confirmed endometriosis, and normal ovarian reserve.
      INTERVENTION(S): All patients underwent endometrial biopsy 9 to 11 days post-LH
      surge to evaluate alpha(v)beta(3) integrin expression. Patients were randomized
      either to receive depot leuprolide acetate 3.75 mg every 28 days for three doses
      before controlled ovarian hyperstimulation (COH) or to proceed directly to COH
      and IVF. Group 1: integrin-positive controls (N = 12); group 2: integrin-positive
      administered prolonged GnRHa (N = 8). Group A: integrin-negative controls (N =
      7); group B: integrin-negative administered prolonged GnRHa (N = 9). MAIN OUTCOME
      MEASURE(S): COH responses, ongoing pregnancy and implantation rates. RESULTS:
      There were no significant effects of GnRH agonist treatment in either of the
      integrin expression strata regarding ongoing pregnancy or implantation rates,
      although these outcomes were more frequent in group 2 vs. 1 (62.5% vs. 41.6% and
      35% vs. 20.6%, respectively). This effect may have because of limited sample
      size. The value of a negative integrin biopsy in predicting an ongoing pregnancy
      after prolonged GnRH agonist therapy was only 44.4%. CONCLUSION(S): Endometrial
      alpha(v)beta(3) integrin expression did not predict which endometriosis patients
      would benefit from prolonged GnRHa therapy before IVF.

PMID- 19171334
TI  - Perceptions of women's infertility: what do physicians see?
AB  - OBJECTIVE: To assess physicians' awareness of the infertility risk associated
      with race, age, and education, and to elicit their clinical management
      recommendations for a hypothetical patient. DESIGN: Cross-sectional survey.
      SETTING: Surveys were mailed to 1,000 randomly selected primary care physicians
      in the state of Michigan. PATIENT(S): None. INTERVENTIONS(S): None. MAIN OUTCOME
      MEASURE(S): Self-reported questionnaire asking the relative prevalence of
      infertility among women based on race, education, and age. Physicians were also
      asked what interventions they would recommend for one of four hypothetical female
      infertility patients who were either European American or African American and
      either a working professional or receiving Medicaid. RESULT(S): Although most
      physicians did not correctly identify the associations between age, race, and
      socioeconomic status and women's infertility, their suggested clinical
      interventions did not vary based on a hypothetical patient's race or
      socioeconomic status. Female physicians, obstetrician/gynecologists, and
      physicians with more infertility experience or who had seen more infertile
      patients recommended more components of a model standard of care. CONCLUSION(S):
      A questionnaire using a hypothetical patient model suggests that primary care
      physicians may not be sufficiently aware of the infertility risk of African
      American women and women with lower socioeconomic status to ensure that women in
      need of services are identified.

PMID- 19171335
TI  - Female obesity impairs in vitro fertilization outcome without affecting embryo
      quality.
AB  - OBJECTIVE: To compare embryo quality and reproductive outcome in our IVF program
      according to the women's body mass index (BMI). DESIGN: Retrospective study.
      SETTING: University-affiliated infertility clinic, between January 2001 and April
      2007. PATIENT(S): Women undergoing a total of 6,500 IVF-intracytoplasmic sperm
      injection (ICSI) cycles. INTERVENTION(S): Six thousand five hundred IVF-ICSI
      cycles were included and divided into four groups: lean (<20 kg/m(2); n = 1,070;
      16.5%); normal (20-24.9 kg/m(2); n = 3,930; 60.5%); overweight (25-29.9 kg/m(2);
      n = 1,081; 16.6%); and obese (> or =30 kg/m(2); n = 419; 6.4%). MAIN OUTCOME
      MEASURE(S): Comparison of embryo quality and reproductive outcome (implantation,
      pregnancy, miscarriage, and live birth rates) among BMI groups. RESULT(S): No
      difference in insemination procedure, fertilization rate, day of ET, mean number
      of transferred and cryopreserved embryos, percentage of blastocyst transfers, or
      embryo quality on day 2 and 3 was found among groups. However, implantation,
      pregnancy, and live birth rates were poorer in obese women. In fact, pregnancy
      and live birth rates were reduced progressively with each unit of BMI (kilograms
      per square meter) with a significant odds ratio of 0.984 (95% confidence interval
      0.972-0.997) and 0.981 (95% confidence interval 0.967-0.995), respectively. In
      addition, the cumulative pregnancy rate after four IVF cycles was reduced as BMI
      increased. CONCLUSION(S): Female obesity impairs IVF outcome, but embryo quality
      is not affected, pointing to an alteration in the uterine environment.

PMID- 19171336
TI  - Gonadotropin-releasing hormone agonist or human chorionic gonadotropin for final
      oocyte maturation in an oocyte donor program.
AB  - OBJECTIVE: To compare leuprolide acetate to hCG as the trigger for final oocyte
      maturation in oocyte donor cycles. DESIGN: Retrospective review. SETTING:
      Academic IVF donor program. PATIENT(S): Thirty-two healthy oocyte donors aged 21
      33 years with adequate ovarian reserve. INTERVENTION(S): Donors were down
      regulated with cetrorelix and received either leuprolide acetate (n = 12) or hCG
      (n = 20) for final oocyte maturation. MAIN OUTCOME MEASURE(S): Embryo number,
      embryo quality, fertilization, implantation, clinical pregnancy, and ovarian
      hyperstimulation syndrome rates. RESULT(S): The numbers of total oocytes (23 vs.
      15), mature (metaphase II) oocytes (22 vs. 13), embryos (15 vs. 10), and
      cryopreserved embryos (12 vs. 6) per treatment cycle were significantly greater
      in the leuprolide arm than in the hCG arm. Fertilization rates (73% vs. 78%),
      implantation rates (30% vs. 29%), and clinical pregnancy rates (40% vs. 50%) were
      not statistically different between the arms. There were no cases of ovarian
      hyperstimulation syndrome. CONCLUSION(S): Leuprolide acetate-triggered oocyte
      donor cycles yielded similar fertilization, implantation, and clinical pregnancy
      rates to hCG-triggered cycles.

PMID- 19171337
TI  - Hepatic steatosis in young lean insulin resistant women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: To investigate the presence of nonalcoholic fatty liver disease
      (NAFLD) in young lean women with polycystic ovary syndrome (PCOS) and insulin
      resistance (IR). DESIGN: Case control study. SETTING: Women with PCOS and healthy
      controls in a metabolic day ward. PATIENT(S): Seventeen young lean women with
      PCOS and 17 matched controls were studied prospectively. INTERVENTION(S): Fasting
      blood and a glucose tolerance test. Ovarian and liver ultrasonography, and
      computed tomography (CT) of the liver (women with PCOS only). MAIN OUTCOME
      MEASURE(S): Anthropometric variables, biochemical and hormonal parameters, and
      several IR indices were determined. Hepatic lipid content was assessed with
      ultrasonography and CT of the liver. RESULT(S): Women with PCOS had higher
      androgen levels, and the IR indices, glucose and insulin area under the curve,
      QUICKI, MATSUDA, and HOMA, compared to controls. In addition to IR, women with
      PCOS had normal aminotransferase levels, and higher, although within the normal
      range, alkaline phosphatase levels compared with controls. Women with PCOS had no
      evidence of NAFLD by either ultrasonography or CT of the liver. CONCLUSION(S):
      Young lean women with PCOS and IR do not have evidence of NAFLD. Because of the
      presence of IR, follow-up is required to determine whether they are at risk of
      developing NAFLD.

PMID- 19171338
TI  - A GnRH agonist and exogenous hormone stimulation protocol has a higher live-birth
      rate than a natural endogenous hormone protocol for frozen-thawed blastocyst
      stage embryo transfer cycles: an analysis of 1391 cycles.
AB  - OBJECTIVE: To compare embryo and birth data in cryopreserved-thawed blastocyst
      stage ET cycles between natural endogenous hormone cycles and exogenous hormone
      stimulation cycles. DESIGN: Retrospective cohort analysis. SETTING: Large
      academic assisted reproductive technology center. PATIENT(S): One thousand three
      hundred ninety-one patient cycles undergoing frozen-thawed blastocyst-stage ET
      cycles. MAIN OUTCOME MEASURE(S): Live-birth rate. INTERVENTION(S): The synthetic
      protocol used GnRH agonist followed by estrogen and P. The natural protocol used
      monitoring and post-transfer P. RESULT(S): The patients in the two protocols had
      similar baseline characteristics. Multiple linear regression showed the synthetic
      protocol to have a higher live-birth rate (odds ratio [OR], 1.46; 95% confidence
      interval [CI], 1.02-2.09). In patients having two embryos transferred, the
      synthetic stimulation protocol resulted in a higher live-birth rate per cycle
      start (32.3% vs. 20.4%; relative risk [RR], 1.58; 95% CI, 1.22-2.06). Similarly,
      patients with one or two embryos transferred who had additional cryopreserved
      blastocysts available also had a higher live-birth rate per cycle start (36.1%
      vs. 12.1; RR, 2.98; 95% CI, 1.16-7.63). CONCLUSION(S): The synthetic hormone
      protocol was associated with a higher live-birth rate when compared with a
      natural cycle protocol for frozen-thawed blastocyst-stage ET cycles. This
      improvement persisted when analysis was controlled for cycle cancellation. The
      synthetic stimulation protocol for frozen-thawed embryo cycles offers improved
      outcome results for patients.

PMID- 19171339
TI  - Duration of strength retention of ankle taping during activities of daily living.
AB  - BACKGROUND AND PURPOSE: Taping has been used for the prevention and treatment of
      ankle injuries. The change in tape strength has not been specifically quantified
      during activities of daily living (ADL) by any investigation so far. Therefore
      the primary aim of this study was to investigate the change in ankle tape
      strength over a 24-h period, while subjects performed their ADL. SUBJECTS: Twenty
      four healthy subjects (mean age: 24.3+/-7.4) participated in this study. METHODS:
      Ankle taping was applied to all subjects for a 24-h period. Outcome measures were
      recorded at six different time intervals and are as follows: before and
      immediately after taping, 15, 30, 60 min, and 24h post taping. Strength of tape
      was quantified as the moment required to rotate the foot passively into
      inversion, measured using a handheld dynamometer. The range of motion (ROM) was
      also measured using a goniometer. The muscle activity of the ankle evertors were
      monitored while recording the outcome measures to ensure that the passive
      rotation of the ankle into inversion by the investigator was not impeded by their
      contraction. RESULTS: A significant change in the moment required to rotate the
      foot into inversion and ROM was found between all time intervals tested
      (p<0.001). There was a 58% reduction in MOM and a 155% increase in ROM after 24h.
      DISCUSSION AND CONCLUSION: This study has quantified for the first time the
      reduction in the support provided by ankle taping while subjects performed their
      ADL. This can assist clinicians on deciding the frequency of tape reapplication
      that may required to provide adequate support to the ankle.

PMID- 19171340
TI  - National data of 6409 Swedish inpatients with femoral shaft fractures: stable
      incidence between 1998 and 2004.
AB  - INTRODUCTION: Femoral shaft fractures are commonly thought to be primarily
      associated with high-energy trauma in young persons. Only limited attention has
      been given to low-energy violence as a cause of these fractures among the
      elderly. National epidemiological data on characteristics of patients with
      femoral shaft fractures are lacking, so the purpose of this study was to analyse
      the incidence, admissions, causes of fracture and operations for these fractures
      on a nationwide basis in Sweden during 1998-2004. PATIENTS AND METHODS: Data on
      all femoral shaft fractures were extracted from the Swedish National Hospital
      Discharge Registry. Sex- and age-specific fracture incidence, hospital
      admissions, mechanisms of injury and surgical procedures were analysed using
      descriptive analysis, linear-regression analysis and other methods as
      appropriate. RESULTS: Over a period of 7 years, 6409 patients with femoral shaft
      fractures were identified, corresponding to an annual incidence of 10 per 100,000
      person-years. Men had a younger median age (27 years, IQR 12-68) than women (79
      years, IQR 62-86) (p<0.001). Females (54%) generated more admissions than males
      (46%). The incident rate ratio between men and women was 0.9 (p<0.001). Most
      hospital admissions were generated among females by the 80-89 years age-group and
      among males <10 years of age. 2% of the fractures were open fractures. The total
      number of hospital admissions was stable during 1998-2004. The two major
      mechanisms of injury were falls on the same level (50%) and transport accidents
      (17%). A significant number of fractures occurred among elderly patients after
      low-energy trauma. Osteosynthesis with femoral nail (54%) was the preferred
      operation, followed by osteosynthesis with plate and screws (16%), skeletal
      traction (14%) and external fixation (6%). DISCUSSION: This nationwide study on
      femoral shaft fractures provides an update on incidence, admissions, external
      causes and surgical procedures. This information assists health-care providers in
      planning hospital beds, surgical interventions and risk preventions. Moreover,
      these data can be used for power calculations for further clinical studies.

PMID- 19171341
TI  - Effect of aortic valve stenosis on haemostasis is independent from vascular
      atherosclerotic burden.
AB  - OBJECTIVE: The aim of study was to assess whether activation of blood coagulation
      and platelets is enhanced in aortic stenosis (AS) and if so, to determine factors
      that might modulate these processes. PATIENTS/METHODS: Seventy-five patients with
      AS (48 males, 27 females, aged 65+/-10 years) were enrolled in the study. A
      control group comprised 75 age- and sex-matched subjects. We determined markers
      of thrombin generation (thrombin-antithrombin complex [TAT], prothrombin fragment
      1+2 [F1+2]), platelet activation (soluble CD40 ligand [sCD40L], beta
      thromboglobulin [beta-TG], P-selectin) in peripheral blood plasma. The extent of
      atherosclerosis in the carotid and coronary arteries was assessed as a potential
      confounding factor. RESULTS: Mean concentrations of thrombin and platelet markers
      were higher approximately two-fold in the AS group than in controls (p<0.005 for
      all comparisons). Maximal gradient was positively associated with TAT (r=0.61,
      p<0.001), F1+2 (r=0.60, p<0.001), sCD40L (r=0.52, p<0.01) and beta-TG (r=0.70,
      p<0.001). Aortic valve area (AVA) negatively associated only with one platelet
      marker, beta-TG (r=-0.30, p<0.05). The presence of concomitant atherosclerotic
      plaque in the carotid (in 65% of patients) or coronary arteries (in 43% of
      patients) did not influence thrombin generation and platelet activation in
      patients with AS. CONCLUSIONS: AS predisposes to prothrombotic state. Maximal
      gradient as an index of turbulent flow associated with activation of coagulation
      and platelets. In contrast, the small aortic valve area was not closely related
      to these parameters.

PMID- 19171342
TI  - Usefulness of haptoglobin and serum amyloid A proteins as biomarkers for
      atherothrombotic ischemic stroke diagnosis confirmation.
AB  - OBJECTIVE: To identify protein biomarkers in order to classify ischemic stroke
      subtypes using proteomic analysis and immunoenzymatic tools for clinical
      validation. METHODS AND RESULTS: We performed a proteomic analysis in serum
      samples of 24 patients with ischemic stroke (12 atherothrombotic patients and 12
      cardioembolic patients). In this study, based on two-dimensional electrophoresis
      and mass spectrometry we found four spots whose expression intensity was at least
      four times stronger in atherothrombotic patients than in cardioembolic patients.
      These spots were identified as haptoglobin related protein, serum amyloid A (two
      spots) and haptoglobin alpha chain. We validated the possible value of
      haptoglobin and serum amyloid A in a larger series of patients (n=262) with
      ischemic stroke using ELISA techniques. Haptoglobin levels >1040microg/mL
      identified atherothrombotic patients with 95% sensitivity and 88% specificity
      whereas serum amyloid A levels >160microg/mL identified atherothrombotic patients
      with 91% sensitivity and 83% specificity. CONCLUSIONS: Haptoglobin and serum
      amyloid A are useful biomarkers for atherothrombotic ischemic stroke diagnosis
      confirmation.

PMID- 19171343
TI  - Lack of association of chromosome 9p21.3 genotype with cardiovascular structure
      and function in persons with stable coronary artery disease: The Heart and Soul
      Study.
AB  - OBJECTIVE: Recent large-scale genome-wide association studies have identified a
      novel susceptibility locus on chromosome 9p21.3 that contributes a significant
      attributable risk for myocardial infarction. The phenotypic significance of this
      locus in patients with established coronary artery disease is unknown. We sought
      to compare cardiovascular structure and function in carriers and non-carriers of
      the risk haplotype in a cross-sectional study. METHODS: We genotyped the
      rs1333049 single-nucleotide polymorphism in 593 Caucasian individuals with stable
      coronary artery disease recruited in the Heart and Soul Study. All study subjects
      underwent resting and stress echocardiography. Linear and logistic regression
      models were used to examine the association between the rs1333049 polymorphism
      and echocardiographic parameters of cardiovascular structure and function.
      RESULTS: There was no association between rs1333049 genotype and
      echocardiographic phenotype (left ventricular hypertrophy, systolic dysfunction,
      diastolic dysfunction, inducible ischemia, exercise capacity, mitral annular
      calcification, and aortic plaque). CONCLUSIONS: In a cross-sectional study of
      individuals with stable coronary artery disease, there was no association of
      chromosome 9p21.3 genotype with cardiovascular structure and function.

PMID- 19171344
TI  - Biomechanical properties across trabeculae from the proximal femur of normal and
      ovariectomised sheep.
AB  - The elastic behaviour of trabecular bone is a function not only of bone volume
      and architecture, but also of tissue material properties. Variation in tissue
      modulus can have a substantial effect on the biomechanical properties of
      trabecular bone. However, the nature of tissue property variation within a single
      trabecula is poorly understood. This study uses nanoindentation to determine the
      mechanical properties of bone tissue in individual trabeculae. Using an
      ovariectomised ovine model, the modulus and hardness distribution across
      trabeculae were measured. In both normal and ovariectomised bone, the modulus and
      hardness were found to increase towards the core of the trabeculae. Across the
      width of the trabeculae, the modulus was significantly less in the ovariectomised
      bone than in the control bone. However, in contrast to this hardness was found
      not to differ significantly between the two groups. This study provides valuable
      information on the variation of mechanical material properties in healthy and
      diseased trabecular bone tissue. The results of the current study will be useful
      in finite element modelling where more accurate values of trabecular bone modulus
      will enable the prediction of the macroscale behaviour of trabecular bone.

PMID- 19171345
TI  - Rapid identification of elastic modulus of the interface tissue on dental
      implants surfaces using reduced-basis method and a neural network.
AB  - This paper proposes a rapid inverse analysis approach based on the reduced-basis
      method (RBM) and neural network (NN) to identify the "unknown" elastic modulus
      (Young's modulus) of the interfacial tissue between a dental implant and the
      surrounding bones. In the present RBM-NN approach, a RBM model is first built to
      compute displacement responses of dental implant-bone structures subjected to a
      harmonic loading for a set of "assumed" Young's moduli. The RBM model is then
      used to train a NN model that is used for actual inverse analysis in real-time.
      Actual experimental measurements of displacement responses are fed into the
      trained NN model to inversely determine the "true" elastic modulus of the
      interfacial tissue. As an example, a physical model of dental implant-bone
      structure is built and inverse analysis is conducted to verify the present RBM-NN
      approach. Based on numerical simulation and actual experiments, it is confirmed
      that the identified results are very accurate, reliable, and the computational
      saving is very significant. The present RBM-NN approach is found robust and
      efficient for inverse material characterizations in noninvasive and/or
      nondestructive evaluations.

PMID- 19171346
TI  - Wave attenuation as a measure of muscle quality as measured by magnetic resonance
      elastography: initial results.
AB  - Advances in imaging technologies such as magnetic resonance elastography (MRE)
      have allowed researchers to gain insights into muscle function in vivo. MRE has
      been used to examine healthy and diseased muscle by calculating shear modulus.
      However, additional information can be measured from visualizing a mechanical
      wave as it passes through a tissue. One such measurable quantity is wave
      attenuation. The purpose of this study was to determine if a simple measure of
      wave attenuation could be used to distinguish between healthy and diseased
      muscle. Twenty seven subjects (14 healthy controls, 7 hyperthyroid myopathy
      patients, 6 myositis patients) participated in this study. Wave amplitude was
      determined along a linear profile through the center of the muscle, and an
      exponential decay curve was fit to the data. This measure was able to find
      significant differences in attenuation between healthy and diseased muscle.
      Furthermore, four hyperthyroid myopathy subjects who were tested following
      treatment all showed improvement by this measure. A likely reason for patients
      with hyperthyroid myopathy and myositis behaving similarly is that this
      measurement may reflect similar changes in the muscle extracellular matrix. In
      addition to modulus, attenuation seems to be an important parameter to measure in
      skeletal muscle. Further research is needed to investigate other potential
      measures of attenuation as well as examining other potential measures that can be
      found from visualizing wave propagation. Future studies should also include
      muscle biopsies to confirm that the changes seen are as a result of changes in
      extracellular matrix structure.

PMID- 19171347
TI  - Analysis of fatty acids in sputum from patients with pulmonary tuberculosis using
      gas chromatography-mass spectrometry preceded by solid-phase microextraction and
      post-derivatization on the fiber.
AB  - A method based on solid-phase microextraction (SPME) and post-derivatization on
      the fiber coupled to gas chromatography-mass spectrometry (GC-MS) was developed
      for the analysis of fatty acids in sputum from patients with pulmonary
      tuberculosis. The sputum specimens were digested, hydrolyzed, extracted,
      derivertized, injected and analyzed without cultivation or isolation of the
      microorganism. Under optimized conditions, the relative standard deviations (RSD,
      n=5) for all analytes were below 17% and the limits of detection varied from 1.68
      (C(24:0)) to 150.4 microg L(-1) (C(12:0)). Good linearity was observed for all
      the fatty acids studied except for C(12:0) within a wide concentration range of
      three orders of magnitudes with the correlation coefficients ranging from 0.91
      (C(24:0)) to 0.99 (C(14:0)). Fatty acids in sputum specimens from 21 persons were
      directly analyzed using the proposed method. The results show that in all the
      sputum specimens from patients, who were clinically diagnosed with tuberculosis
      (TB), tuberculosis stearic acid (TBSA) was detected, while in all the sputum
      samples from persons without TB, TBSA was not found. The possibility of using the
      proposed method to detect mycobacterium tuberculosis (MTB) via the identification
      of TBSA in sputum was discussed. The comparison with other methods including
      sputum culture and microscopy of direct smears indicated that the proposed method
      is fast and sensitive for the analysis of fatty acids in sputum and offers an
      alternative for the detection of MTB in sputum.

PMID- 19171349
TI  - pH programming in capillary electrophoresis by means of temperature programming.
AB  - When using a background electrolyte with a buffer having strong temperature
      dependence of pK, different operating temperatures result in different operating
      pH values, using the same background electrolyte (BGE). It has been shown that
      this can be used to fine-tune selectivities of sample mixtures of weak analytes.
      Capillary electrophoresis (CE) equipment is designed to operate under isothermal
      conditions, but by proper programming, a very reproducible temperature and thus
      BGE pH program during the analysis can be realized. This was experimentally
      verified and illustrated by computer simulations. Equipment characteristics have
      been determined, and possibilities and restrictions to make use of this feature
      are presented.

PMID- 19171348
TI  - Characterization of fulvic acids by liquid chromatography-quadrupole time-of
      flight mass spectrometry.
AB  - Fulvic acid standards from Suwannee River, Pony Lake, Elliot Soil, Waskish Peat,
      and Nordic Reservoir were characterized by liquid chromatography coupled to
      quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) operating in negative
      electrospray ionization mode. The method employed a commercially available
      stationary phase that resulted in a distinctive chromatographic peak for each of
      the fulvic acid samples that differed in width and retention time at peak
      maximum. The QTOF-MS, operating in TOF mode, revealed that the unique
      chromatographic peak shapes were the result of the relative fraction of hydrogen
      and oxygen contained in various fulvic acid components. Those species that
      contained larger amount of hydrogen displayed a larger mass defect and were
      retained longer on the LC column, indicating reduced polarity. This is supported
      by a reduction in the degree of fragmentation related to polar functional groups
      as the mass defect and retention time increased. Lastly, the analysis of even and
      odd mass (at m/z 1 greater) ion intensity ratios revealed a correlation to the
      percent nitrogen of the various standards.

PMID- 19171350
TI  - Quality control of traditional Chinese medicines. Foreword.

PMID- 19171351
TI  - A symposium is a unique opportunity to exchange ideas. Foreword.

PMID- 19171352
TI  - Enzyme enhanced quantitative determination of multiple DNA targets based on
      capillary electrophoresis.
AB  - In the current paper, enzyme enhanced simultaneous quantitative determination of
      multiple DNA targets based on capillary electrophoresis (CE) was described. We
      used three biotin-modified DNA probes, which reacted with avidin-conjugated
      horseradish peroxidase (avidin-HRP) conjugate to obtain the HRP labeled probes,
      to hybridize with three corresponding targets. The resulting mixture containing
      double-strand DNA (dsDNA)-HRP, excess single-strand DNA (ssDNA)-HRP and remaining
      avidin-HRP was separated by capillary electrophoresis, and then the system of HRP
      catalyzing H(2)O(2)/o-aminophenol (OAP) reaction was adopted. The catalytic
      product was detected with electrochemical detection. With this protocol, the
      limits of quantification for the hybridization assay of 21-, 39- and 80-mer DNA
      fragments were of 1.2 x 10(-11), 2.4 x 10(-11) and 3.0 x 10(-11)M, respectively.
      The multiplex assay also provided good specificity without any cross-reaction.

PMID- 19171353
TI  - Improved determination of milk oligosaccharides using a single derivatization
      with anthranilic acid and separation by reversed-phase high-performance liquid
      chromatography.
AB  - An improved analytical scheme for human milk neutral oligosaccharides
      determination was developed, in which, the oligosaccharides were pooled in two
      fractions (pools 1 and 2) after gel filtration, and then were quantitatively
      derivatized with a single fluorescent reagent, 2-anthranilic acid. Separation was
      by reversed-phase HPLC on an ODS-100Z column with a mobile phase of 50 mM
      ammonium acetate pH 4.0 and 150 mM citrate buffer pH 4.5 and monitored by a
      fluorescence detector at 360nm excitation and 425 nm emission wavelengths. The
      method improved on the separation of neutral tetra- and hexa-saccharide isomers,
      namely, lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) as well as of lacto
      N-difucohexaose I (LNDFH I) and lacto-N-difucohexaose II (LNDFH II). The
      separation of trisacccharide isomers, 3-fucosyllactose (3-FL) and 2'
      fucosyllactose (2'-FL) was also successful. Limits of detection and
      quantification were in the range of 1-10 ng/l and 2-30 ng/l, respectively. The
      methods' accuracy was good with its precision at <20% RSD and <1% RSD,
      respectively, for oligosaccharide concentration and retention time. The
      recoveries were in the range of 80-100%. This method was successfully applied to
      the separation and determination of representative neutral oligosaccharide
      contents in Samoa women milk.

PMID- 19171354
TI  - CCR7+ myeloid dendritic cells together with CCR7+ T cells and CCR7+ macrophages
      invade CCL19+ nonnecrotic muscle fibers in inclusion body myositis.
AB  - CCR7 and its ligands CCL19 and CCL21 are a key chemokine system in T cell priming
      in secondary lymphoid organs, and are rarely expressed in normal muscle tissue.
      We immunohistochemically investigated the expression of this chemokine system in
      the muscles of seven patients with inclusion body myositis (IBM). In all cases,
      CCR7+ mononuclear cells infiltrated in the endomysium, preferentially surrounded
      and invaded nonnecrotic muscle fibers. Double immunostaining revealed that such
      CCR7+ mononuclear cells included BDCA-1+ myeloid dendritic cells as well as CD8+
      cells, CD4+ cells and CD68+ macrophages. On the other hand, CCL19 was widely
      expressed on muscle fibers including those invaded by mononuclear cells. CCL19
      was also expressed diffusely on endomysial mononuclear cells and endothelium of
      vessels. Immunoreactivities of CCL21 were detected on some muscle fibers and
      mononuclear cells. By RT-PCR analyses, mRNA of CCR7 was detected in all the
      patients and that of CCL19 and CCL21 was detected in six. These findings showed
      that the CCL19, CCL21/CCR7 chemokine system is expressed in muscles of IBM. The
      chemokine mediated attraction in dendritic and other immune cells and muscle
      cells may be crucial in sustained antigen presentation, T cell activation and
      immune attack to muscles in the pathogenesis of IBM.

PMID- 19171355
TI  - Immunomodulation of EAE by alpha-fetoprotein involves elevation of immune cell
      apoptosis markers and the transcription factor FoxP3.
AB  - Alpha-fetoprotein (AFP) is an immunomodulatory glycoprotein associated with the
      normal growth of the mammalian fetus. Ws have shown that treatment with
      recombinant human AFP (rhAFP) reduced lymphocyte reactivity and the extent of
      neuroinflammation in mice with experimental autoimmune encephalomyelitis (EAE).
      In the present study we found involvement of AFP in immune cell apoptosis,
      attesting to its possible mechanism of action. AFP increased the expression of
      the Bax, Bid, Bad and ApaF genes in peripheral lymphocytes, together with an
      enhanced expression of Caspase-3, Fas, FasL and TRAIL among infiltrating immune
      cells. The induction of apoptosis markers was accompanied with an increased
      expression of Foxp3 in lymph node cells, as well as accumulation of CD4+Foxp3+
      regulatory T cells in the CNS. Overall, these immunological alterations gave rise
      to a milder disease and accelerated remission rate. Our results suggest a new
      role for AFP in controlling the autoimmune inflammation associated with EAE.

PMID- 19171356
TI  - Alternatives to transtemporal approach of transcranial Doppler for the detection
      of right-to-left cardiac shunt.
AB  - BACKGROUND: Transcranial Doppler (TCD) is reliable and reproducible for the
      diagnosis of right-to-left cardiac shunts (RLS). METHODS: Various factors
      limiting the performance and diagnostic methods of RLS by TCD are discussed.
      RESULTS: In patients with insufficient temporal acoustic windows, TCD may still
      be reliably used to monitor the microembolic signals at various alternative
      sites. Diagnostic yield of TCD may be further improved and better quantitative
      assessment of the 'functional potential' of the RLS by optimizing the preparation
      of the 'air-saline-blood' contrast-mixture, injecting the mixture in controlled
      body positions and using power M-mode TCD. CONCLUSIONS: TCD may be used reliably
      for the detection as well as the quantification of RLS even in patients with
      insufficient temporal acoustic windows.

PMID- 19171357
TI  - Toyocamycin specifically inhibits auxin signaling mediated by SCFTIR1 pathway.
AB  - The auxins, plant hormones, play a crucial role in many aspects of plant
      development by regulating cell division, elongation and differentiation.
      Toyocamycin, a nucleoside-type antibiotic, was identified as auxin signaling
      inhibitor in a screen of microbial extracts for inhibition of the auxin-inducible
      reporter gene assay. Toyocamycin specifically inhibited auxin-responsive gene
      expression, but did not affect other hormone-inducible gene expression.
      Toyocamycin also blocked auxin-enhanced degradation of the Aux/IAA repressor
      modulated by the SCF(TIR1) ubiquitin-proteasome pathway without inhibiting
      proteolytic activity of proteasome. Furthermore, toyocamycin inhibited auxin
      induced lateral root formation and epinastic growth of cotyledon in the
      Arabidopsis thaliana plant. This evidence suggested that toyocamycin would act on
      the ubiquitination process regulated by SCF(TIR1) machineries. To address the
      structural requirements for the specific activity of toyocamycin on auxin
      signaling, the structure-activity relationships of nine toyocamycin-related
      compounds, including sangivamycin and tubercidin, were investigated.

PMID- 19171358
TI  - [Massive sinus-lift procedures with beta-tricalcium phosphate: long-term
      results].
AB  - INTRODUCTION: The use of bone substitutes in massive sinus-lift pre-implant
      procedures remains controversial. The aim of our study was to evaluate the long
      term reliability of pure-phase beta-tricalcium phosphate (betaTCP, Cerasorb,
      Curasan, Kleinostheim, Germany) used in this particular indication. MATERIAL AND
      METHOD: Twenty patients (33sinus) presenting with severe sinus floor atrophy
      (class 4 to 6 according to Cawood) and having undergone a sinus lift procedure by
      mean of betaTCP were followed in a prospective study between January 2002 and May
      2008. The surgical approach was classical (under local anesthesia in eight
      patients) and the sinuses were filled with betaTCP (6 cm3 on average per sinus)
      and autologous growth factors (platelet rich plasma PRP and platelet rich fibrin
      PRF, according to the technique described by Dohan and Weibrich). One hundred and
      twenty-three dental implants were inserted in the grafted sinuses between the
      fourth and the eighth postoperative month (Nobel Biocare MK III and MK IV-mean
      length: 12.44 mm) using a 2-step buried technique and loaded between the fourth
      and the sixth month. Follow-up included regular clinical examination and
      panoramic X-rays to screen for possible sinus and implant complications. The
      control X-rays also allowed measuring the biomaterial resorption rate. RESULTS:
      The mean postoperative follow-up was 4.5 years for the sinus lift procedures and
      4 years for the implants. We noted one case of local infection at the 15th
      postoperative day (3%). The implant success rate was 97.6% (lack of osteo
      integration for two implants in the same patient, one failure after loading). The
      prosthetic success rate was 100%. The mean resorption rate of the material was
      20.3% and the mean gain of height was 16.9 mm. DISCUSSION: The use of betaTCP
      associated to growth factors (PRP ou PRF) without bone graft, in massive sinus
      lift procedures induces few complications. The implant success rate is comparable
      to the one obtained by using autologous bone grafts. The resorption rate of the
      material is comparable to that of autologous bone.

PMID- 19171359
TI  - Improving control of African schistosomiasis: towards effective use of rapid
      diagnostic tests within an appropriate disease surveillance model.
AB  - Contemporary control of schistosomiasis is typically reliant upon large-scale
      administration of praziquantel (PZQ) to school age children. Whilst PZQ treatment
      of each child is inexpensive, the direct and indirect costs of preventive
      chemotherapy for the whole school population are more substantive and, at the
      national level where many schools are targeted, maximising cost effectiveness and
      the health impact are essential requirements for ensuring longer-term
      sustainability (i.e. >5 years). To this end, the WHO has issued a set of
      treatment guidelines, inclusive of re-treatment schedules, such that, where
      possible, treatment decisions by school are based upon local disease prevalence
      as determined by parasitological and/or questionnaire methods. As each diagnostic
      method has known shortcomings, presumptive treatment of at-risk schools may
      initially be preferred, especially if the existing infrastructure for disease
      surveillance is poor. It is against this background of school-based preventive
      chemotherapy that a rapid diagnostic test (RDT) for schistosomiasis is most
      urgently needed, not only to improve initial disease surveillance but also to
      focus drug delivery better through time. In this paper, the development,
      evaluation and application of selected diagnostic tests are reviewed to identify
      barriers that impede progress, foremost of which is that a new disease
      surveillance and evaluation model is required where the in-country price of each
      RDT ideally needs to be less than US$1 to be cost effective both in the short-
      and long-term perspective.

PMID- 19171360
TI  - Characterisation of atmospheric deposition as a source of contaminants in urban
      rainwater tanks.
AB  - To characterise atmospheric input of chemical contaminants to urban rainwater
      tanks, bulk deposition (wet+dry deposition) was collected at sixteen sites in
      Brisbane, Queensland, Australia on a monthly basis during April 2007-March 2008
      (N=175). Water from rainwater tanks (22 sites, 26 tanks) was also sampled
      concurrently. The deposition/tank water was analysed for metals, soluble anions
      and selected samples were additionally analysed for PAHs, pesticides, phenols,
      organic & inorganic carbon. Flux (mg/m(2)/d) of total solids mass was found to
      correlate with average daily rainfall (R(2)=0.49) indicating the dominance of the
      wet deposition contribution to total solids mass. On average 97% of the total
      mass of analysed components was accounted for by Cl(-) (25.0%), Na (22.6%),
      organic carbon (20.5%), NO(3)(-) (10.5%), SO(4)(2-) (9.8%), inorganic carbon
      (5.7%), PO(4)(3-) (1.6%) and NO(2)(-) (1.5%). For other minor elements the
      average flux from highest to lowest was in the order of
      Fe>Al>Zn>Mn>Sr>Pb>Ba>Cu>Se. There was a significant effect of location on flux of
      K, Sb, Sn, Li, Mn, Fe, Cu, Zn, Ba, Pb and SO(4)(2-) but not other metals or
      anions. Overall the water quality resulting from the deposition (wet+dry) was
      good but 10.3%, 1.7% and 17.7% of samples had concentrations of Pb, Cd and Fe
      respectively greater than the Australian Drinking Water Guidelines (ADWG). This
      generally occurred in the drier months. In comparison 14.2% and 6.1% of tank
      samples had total Pb and Zn concentrations exceeding the guidelines. The
      cumulative mean concentration of lead in deposition was on average only 1/4 of
      that in tank water over the year at a site with high concentrations of Pb in tank
      water. This is an indication that deposition from the atmosphere is not the major
      contributor to high lead concentrations in urban rainwater tanks in a city with
      reasonable air quality, though it is still a significant portion.

PMID- 19171361
TI  - The use of microemulsions to remove chromium from industrial sludge.
AB  - In this work microemulsion systems were used to remove chromium from leather
      tannery sediments. The sludge was treated by a solid-liquid extraction process
      (acid digestion). The effects of particle size, digestion temperature and
      digestion time with regards to the efficiency of chromium removal were
      considered. The raw sludge (3 Mesh) was dried, grounded and sieved. Particles
      with 3, 14, 65, 100, 200, and 325 Mesh were evaluated. Sludge digestion solutions
      were prepared using each studied granule size at 25 degrees C, 70 degrees C, and
      95 degrees C. Microemulsion extraction experiments to remove chromium III from
      the acid digestion solution were made according to a Scheffe Net experimental
      design methodology, using microemulsion systems inside the Winsor II region
      (System I) and inside the microemulsion region (Winsor IV--System II). A
      statistical treatment was used to obtain the isoresponse plots. Chromium
      extraction percentages were up to 73.3% for System I and up to 93.4% for System
      II.

PMID- 19171362
TI  - Deactivation and transformation products in biodegradability testing of beta
      lactams amoxicillin and piperacillin.
AB  - Antibiotics have increasingly been detected in effluents and the environment.
      However, information on the degree of deactivation and mineralization, and the
      nature of possible formed dead-end transformation products is scarce but
      desirable for proper risk assessment. An important group of antibiotics is the
      beta-lactams. We studied the transformation of the closely structurally related
      beta-lactams piperacillin and amoxicillin in two OECD biodegradability batch
      tests. None of the antibiotics was biodegraded in the closed bottle test (CBT).
      However, primary abiotic elimination as monitored by HPLC-UV-VIS was 20% and 100%
      in the CBT within 14 days, respectively. With HPLC-UV-VIS and ion trap LC-MS/MS
      primary elimination was shown to be more than 94% for both antibiotics within
      seven days in the Zahn-Wellens test (ZWT). Both compounds were deactivated by
      hydrolysis. For piperacillin, a dead-end transformation product resulted after
      hydrolysis of the beta-lactam ring. For amoxicillin full mineralization of the
      transformation products was observed.

PMID- 19171363
TI  - Microwave activated electrochemical degradation of 2,4-dichlorophenoxyacetic acid
      at boron-doped diamond electrode.
AB  - A method for improving the oxidation ability of the electrode is proposed by
      using microwave activation in electrochemical oxidation. The electrochemical
      degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) with microwave radiation
      (MW-EC) was carried out in a continuous flow system under atmospheric pressure.
      In 3 h the removal of COD, ACE (average current efficiency) and Cl(-)
      concentration was 1.63, 2.25 and 1.67 times as that without microwave radiation,
      respectively. The high degradation ability was resulted from the more active
      centers at the electrode surface due to the microwave radiation. The decay
      kinetics of 2,4-D followed a pseudo first-order reaction. The rate constant was
      increased to 2.16x10(-4) s(-1) with the microwave radiation, while it was
      8.52x10(-5) s(-1) with electrochemical treatment only (EC). Under both
      conditions, the main intermediates were identified and quantified by High
      Performance Liquid Chromatography (HPLC). The formation rate of intermediate
      products and further degradation rate were increased by about 50-120% with the
      microwave radiation. The activation of electrochemical oxidation by microwave was
      discussed from the diffusion process, adsorption and the temperature at boron
      doped diamond (BDD) electrode.

PMID- 19171364
TI  - Effects of varying combustion conditions on PCDD/F emissions and formation during
      MSW incineration.
AB  - Process, combustion and fuel parameters were varied to elucidate factors that
      substantially affect the formation and emissions of polychlorinated dibenzo-p
      dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) arising from municipal
      solid waste (MSW) incineration. The combustion conditions were varied by changing
      the: freeboard temperatures; quench time in the post-combustion zone; fuel load;
      chlorine and copper levels in the fuel; and the water, sulfur dioxide, carbon
      monoxide and oxygen levels in the combustion gases. The study was performed using
      a 5kW laboratory-scale fluidized-bed reactor and PCDD/Fs were sampled at a point
      at 300 degrees C in the post-combustion zone. The results showed that increasing
      the SO(2) level (from 0 to 130ppm) substantially reduced the PCDD/F emissions, by
      up to 60%. In contrast, increasing the CO levels (due to transient combustion
      conditions), raising the Cl level (from 0.7% to 1.7%) and reducing the freeboard
      temperature (from 800 degrees C to 660 degrees C) all substantially increased the
      emission levels (more than 3-fold). Changes in PCDD/F profiles associated with
      increases in Cl, SO(2) or CO levels and increasing the freeboard temperature
      (from 800 degrees C to 950 degrees C) indicate that the PCDFs were mainly formed
      by chlorination. In addition, increasing the Cl level increased the chlorination
      activity in the formation of PCDDs. Increasing the SO(2) level appeared to be
      less effective in reducing the amount of PCDDs formed via the precursor pathway.
      While increased CO levels induced PCDD formation via the precursor pathway,
      although this was found to depend on the O(2) level in the flue gas.

PMID- 19171365
TI  - Allelochemical stress causes oxidative damage and inhibition of photosynthesis in
      Chlorella vulgaris.
AB  - This study investigated the effects of N-phenyl-2-naphthylamine, an effective
      allelochemical on aquatic unicellular algae Chlorella vulgaris at physiological
      gene transcription level. Exposure to 2.5 mg L(-1) of N-phenyl-2-naphthylamine
      increased the activities of the antioxidant enzymes, superoxide dismutase (SOD),
      peroxidase (POD), and catalase (CAT), which were 2.47, 3.24, and 4.27 times
      higher than that of the control, however, exposure to 4.0 mg L(-1) N-phenyl-2
      naphthylamine decreased the activities of these antioxidant enzymes. An increase
      in malondialdehyde content and a decrease in chlorophyll content following
      exposure to N-phenyl-2-naphthylamine suggested that the alga was severely damaged
      and that cell growth was greatly inhibited. Electron microscopy showed that the
      plasma membrane was detached from the cell wall, the nucleus was condensed, and
      the structure of chloroplasts was disrupted, in response to N-phenyl-2
      naphthylamine exposure. Real-time PCR showed that N-phenyl-2-naphthylamine
      reduced the transcript abundance of psaB and psbC to 3% and 1% of the control,
      respectively. These results demonstrated that N-phenyl-2-naphthylamine not only
      inhibited photosynthesis, but also triggered the synthesis of reactive oxygen
      species (ROS) to disrupt the subcellular structure of this aquatic organism.

PMID- 19171366
TI  - Immunomodulation in the marine gastropod Haliotis diversicolor exposed to
      benzo(a)pyrene.
AB  - It has been reported that environmental pollutants in the aquatic ecosystem could
      weaken immune competence of organisms. The purpose of the present study was to
      investigate the effects of benzo(a)pyrene [B(a)P] on immunomodulation in marine
      gastropods and to see if these effects are caused by or related to the generation
      of reactive oxygen species. In our present study, the marine gastropod Haliotis
      diversicolor was exposed to sublethal concentrations (0.01, 0.02, 0.04 and 0.08
      mg L(-1)) of B(a)P for 7d under laboratory conditions and the alterations of
      hematological parameters like haemocyte count, haemocyte viability, protein
      content and immune components like phenoloxidase, phagocytosis and superoxide
      anion generation were measured. In addition, the changes in lysozyme activity,
      antibacterial activity due to the effect of B(a)P on abalone were analysed. B(a)P
      was found to decrease significantly the total number of circulating haemocytes.
      Intracellular superoxide anion generation and phenoloxidase significantly
      increased on exposure to B(a)P, whereas phagocytic activity was decreased
      significantly at higher concentration. Significant alterations were found in the
      uptake of neutral red and the observed alterations of hematological parameters
      and immune components tested indicated the generation of immunotoxicological
      effects on abalone due to B(a)P exposure. The results demonstrate a possible
      relationship between B(a)P and the immunological parameters of abalone studied.

PMID- 19171367
TI  - Accumulation of 242Pu by a macrophyte of the Yenisei River (Elodea canadensis) in
      laboratory experiments.
AB  - The study addresses 242Pu accumulation by Elodea canadensis, one of the abundant
      species of submerged plants in the Yenisei River. 242Pu in water samples of the
      "Elodea-Yenisei River water" model system and in the biomass fractions was
      determined alpha-spectrometrically, following radiochemical recovery of 242Pu
      using 236Pu--a chemical yield tracer. The experiments on accumulation of 242Pu by
      Elodea biomass showed that the activity concentration of 242Pu can reach 21 +/- 2
      Bq/g dry wt, with the concentration factor for 242Pu 13100 +/- 2100 L/kg dry wt.
      Results of chemical fractionation proved that during the first few hours of the
      experiment 242Pu contained in Elodea was mainly concentrated in the exchangeable
      and the adsorbed fractions of biomass (about 100%). As Elodea biomass accumulated
      242Pu, the absolute amount of 242Pu in the exchangeable and the adsorbed
      fractions remained almost unchanged, although the portion of 242Pu tightly bound
      to biomass increased. At the end of the experiment, on day 7, 242Pu tightly bound
      to biomass (fractions of organics and mineral residue) constituted 43-63% (in
      different experiments) of the total 242Pu in the biomass.

PMID- 19171368
TI  - Bioaugmentation for chlorinated ethenes using Dehalococcoides sp.: comparison
      between batch and column experiments.
AB  - Batch and column experiments were performed to evaluate the transport, growth and
      dechlorination activity of Dehalococcoides sp. (DHC) during bioaugmentation for
      chlorinated ethenes. Batch experiments showed that the reductive dechlorination
      of trichloroethene (TCE), cis-1,2-dichloroethene (DCE), and vinyl chloride (VC),
      as well as growth of the DHC, were well described by the Monod kinetic model. The
      measured maximum utilization rate coefficients for TCE, DCE, and VC were 1.3x10(
      12), 5.2x10(-13), and 1.4x10(-12)mmol Cl(-) (cellh)(-1), respectively. Results of
      the column experiments showed that dechlorination occurred throughout the length
      of the column, and that extractable DHC concentrations associated with the soil
      phase throughout the column were negligible relative to the aqueous phase
      concentrations. Dechlorination rates relative to aqueous DHC concentrations in
      the column were approximately 200-times greater than in the batch experiments.
      Additional batch experiments performed using column effluent water confirmed this
      result. Incorporation of these enhanced dechlorination kinetics in the transport
      model provided a reasonable prediction of the column data. Overall results of
      this study suggest that aqueous phase (as opposed to soil phase) DHC
      concentrations can be used to estimate dechlorination activity in saturated
      soils, and DHC dechlorination activity in porous media may be substantially
      greater than DHC dechlorination activity measured in batch experiments.

PMID- 19171369
TI  - Correlation of PCDD/F and PCB at combustion experiments using wood and hospital
      waste. Influence of (NH(4))(2)SO(4) as additive on PCDD/F and PCB emissions.
AB  - The objectives of this work were to study the emissions of polychlorinated
      dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/F) and polychlorinated
      biphenyl (PCB) during the combustion of wood, wood and hospital waste as well as
      wood, hospital waste and (NH(4))(2)SO(4) in a pilot plant and to determine the
      relation of the toxic emissions to the fuel properties. The presence of PVC
      (experiments b and c) increases PCDD/F and PCB formation compared to burning only
      eco-farm wood (a). However, analysis and quantification of PCDD/F and PCB showed
      that the amount of 5% of (NH(4))(2)SO(4) in the fuel mixture significantly
      impacted the dioxins emissions and suppressed it by approximately 50%. In
      addition, longer duration of the combustion experiment by using (NH(4))SO(4)
      resulted in a stronger inhibition of the toxic emissions. Overall, the lowest
      values were observed during the combustion of the fuel blends containing wood
      only. Relationships of PCDD/F (WHO-TEQ) and individual congeners of WHO-PCDD/F,
      WHO-PCB and six PCB indicator congeners were also found. As a result, all single
      PCB congeners were identified as PCDD/F (WHO-TEQ) surrogates in the flue gas.
      Furthermore, the correlation between PCDD/F and PCB congeners was examined by
      statistical methods such as cluster analysis (CA). Closely neighboured pairs on
      the dendrogram were additionally confirmed by a high linear coefficient of
      determination (R(2)). (NH(4))(2)SO(4)-containing samples did not affect the
      correlations between PCDD/F and PCB at the concentrations given.

PMID- 19171370
TI  - Extracellular plant DNA in Geneva groundwater and traditional artesian drinking
      water fountains.
AB  - DNA, as the signature of life, has been extensively studied in a wide range of
      environments. While DNA analysis has become central to work on natural gene
      exchange, forensic analyses, soil bioremediation, genetically modified organisms,
      exobiology, and palaeontology, fundamental questions about DNA resistance to
      degradation remain. This paper investigated on the presence of plant DNA in
      groundwater and artesian fountain (groundwater-fed) samples, which relates to the
      movement and persistence of DNA in the environment. The study was performed in
      the groundwater and in the fountains, which are considered as a traditional
      artesian drinking water in Geneva Champagne Basin. DNA from water samples was
      extracted, analysed and quantified. Plant gene sequences were detected using PCR
      amplification based on 18S rRNA gene primers specific for eukaryotes.
      Physicochemical parameters of water samples including temperature, pH,
      conductivity, organic matter, dissolved organic carbon (DOC) and total organic
      carbon (TOC) were measured throughout the study. The results revealed that
      important quantities of plant DNA can be found in the groundwater. PCR
      amplification based on 18S rDNA, cloning, RFLP analysis and sequencing
      demonstrated the presence of plant DNA including Vitis rupestris, Vitis
      berlandieri, Polygonum sp. Soltis, Boopis graminea, and Sinapis alba in the water
      samples. Our observations support the notion of plant DNA release, long-term
      persistence and movement in the unsaturated medium as well as in groundwater
      aquifers.

PMID- 19171372
TI  - Electro-photocatalytic degradation of acid orange II using a novel TiO2/ACF
      photoanode.
AB  - A novel photoanode was prepared by immobilizing TiO(2) film onto activated carbon
      fibers (TiO(2)/ACF) using liquid phase deposition (LPD) to study the electro
      photocatalytic (EPC) degradation of organic compounds exemplified by an azo-dye,
      namely, Acid Orange II (AOII). Results demonstrated that by applying a 0.5 V bias
      (vs. SCE) across the TiO(2)/ACF electrode, the AOII degradation rate was
      increased significantly compared to that of photocatalytic (PC) oxidation. The
      application of an electric field promotes the separation of photogenerated
      electrons and holes as confirmed by electrochemical impedance spectroscopy (EIS)
      measurements. The structural and surface morphology of the TiO(2)/ACF electrode
      was characterized by field emission scanning electron microscopy (FE-SEM) and X
      ray diffraction (XRD). SEM images showed that TiO(2) was deposited on almost
      every carbon fiber with an average thickness of about 200 nm with the inner space
      between neighboring fibers being maintained unfilled. The morphological features
      of the photo-anode facilitated the passage of solution as well as UV light
      through the felt-form electrode and created a three-dimensional environment
      favorable to EPC oxidation. Both the large outer surface area of the 3D electrode
      and the good organic adsorption capacity of the ACF support promoted high contact
      efficiency between AOII and TiO(2) surface. Anatase was the major crystalline
      TiO(2) deposited. UV-vis spectrophotometry, TOC (total organic carbon) analysis,
      and HPLC technique were used to monitor the concentration change of AOII and
      intermediates as to gain insight into the EPC degradation of AOII using the
      TiO(2)/ACF electrode.

PMID- 19171371
TI  - Effects of 17beta-estradiol, and its metabolite, 4-hydroxyestradiol on
      fertilization, embryo development and oxidative DNA damage in sand dollar
      (Dendraster excentricus) sperm.
AB  - Oxidative compounds have been demonstrated to decrease the fertilization
      capability and viability of offspring of treated spermatozoa. As estrogen and its
      hydroxylated metabolites readily undergo redox cycling, this study was undertaken
      to determine if estrogens and other oxidants could damage DNA and impair sperm
      function. Sperm was preexposed to either 17beta-estradiol (E2), 4
      hydroxyestradiol (4OHE2) or the oxidant t-butyl hydroperoxide (t-BOOH), and
      allowed to fertilize untreated eggs. The fertilization rates and development of
      the larvae were assessed, as well as the amount of 8-oxodeoxyguanosine (8-oxodG)
      as an indication of oxidative DNA damage. All compounds caused significant
      decreases in fertilization and increases in pathological abnormalities in
      offspring, with 4OHE2 being the most toxic. Treatment with 4OHE2 caused a
      significant increase of 8-oxodG, but E2 failed to show any effect. Pathological
      abnormalities were significantly correlated (r(2)=0.44, p< or =0.05) with 8-oxodG
      levels in sperm treated with t-BOOH and 4OHE2, but not E2. 8-OxodG levels also
      were somewhat weakly correlated with impaired fertilization in 4OHE2-treated
      sperm (r(2)=0.33, p< or =0.05). The results indicate that biotransformation of E2
      to 4OHE2 enhances oxidative damage of DNA in sperm, which can reduce
      fertilization and impair embryonic development, but other mechanisms of action
      may also contribute to these effects.

PMID- 19171374
TI  - Can programmed cell death be induced in post-ejaculatory bull and stallion
      spermatozoa?
AB  - Apoptosis is common during spermatogenesis. Here, it was tested whether apoptosis
      could be induced in sperm after ejaculation. There were several lines of evidence
      to indicate that sperm are resistant to induction of apoptosis. First, incubation
      of bull sperm at temperatures characteristic of normothermia (38.5 degrees C) or
      heat shock (40 and 41 degrees C) for 4h did not increase the proportion of sperm
      positive for the TUNEL reaction. There was also no reduction in mitochondrial
      polarity caused by exposure to 40 or 41 degrees C. Incubation at 38.5 degrees C
      (least-squares mean+/-SEM=4.0+/-1.4%), 40 degrees C (6.2+/-1.4%), and 41 degrees
      C (7.0+/-1.4%) for 24h did increase the proportion of sperm that were TUNEL
      positive slightly as compared to non-incubated control sperm (1.0+/-1.4%).
      However, the increase in TUNEL labeling was not affected by incubation
      temperature and occurred even in the presence of the group II caspase inhibitor,
      z-DEVD-fmk. In addition, exposure of bull sperm to carbonyl cyanide 3
      chlorophenylhydrazone (CCCP), which depolarizes mitochondrial membranes, did not
      increase TUNEL labeling. Stallion sperm were also resistant to increased TUNEL
      labeling in response to incubation at 41 degrees C for 4h or exposure to CCCP.
      Western blotting was performed to determine whether failure of induction of
      apoptosis was due to aberrant caspase activation. Procaspase-9 was detected in
      bull sperm, but cleavage to caspase-9 was not induced by short-term aging at
      38.5, 40, or 41 degrees C, or exposure to CCCP. Procaspase-3 was not detected in
      bull spermatozoa. In conclusion, post-ejaculatory bull and stallion sperm were
      resistant to induction of apoptosis; this resistance, at least in bulls, was due
      to refractoriness of mitochondria to heat shock-induced depolarization, lack of
      activation of procaspase-9, and an absence of procaspase-3.

PMID- 19171373
TI  - Surgical management of borderline ovarian tumors: The role of fertility-sparing
      surgery.
AB  - OBJECTIVE: To evaluate the recurrence, survival, and pregnancy outcomes of
      patients with borderline ovarian tumors (BOT) treated with fertility-sparing
      surgery. METHODS: The medical records of patients with BOT who underwent surgery
      between 1989 and 2008 were retrospectively reviewed. Outcomes were compared
      between groups that underwent radical or fertility-sparing surgery. Fertility
      sparing surgery was defined as the preservation of the uterus and ovarian tissue
      in one or both adnexa. RESULTS: During the study period, 360 patients with BOT
      were identified; of these, 344 had stage I, one had stage II, and 15 had stage
      III disease. A total of 176 patients underwent radical surgery (23
      laparoscopically and 153 laparotomically), and 184 underwent fertility-sparing
      surgery (48 laparoscopically and 136 laparotomically). After surgery, 45 patients
      received adjuvant chemotherapy. After a median follow-up time of 70 months
      (range, 3-216 months), 18 patients had recurrent disease and 5 died of disease.
      The recurrence rate was similar in the radical and fertility-sparing surgery
      groups (4.9% vs. 5.1%, p=0.923). In the fertility-sparing surgery group, however,
      the most common site of recurrence was the remaining ovarian tissue which was
      successfully salvaged with a second round of fertility-sparing surgery.
      Multivariate analysis showed no difference in disease-free survival between
      groups that underwent radical or fertility-sparing surgery (p=0.651). To date,
      there have been 34 full-term deliveries by women in the fertility-sparing surgery
      group. CONCLUSIONS: Fertility-sparing surgery for patients with BOT is safe and
      can permit future pregnancy, suggesting that such surgery should be considered
      for young patients who wish to preserve fertility.

PMID- 19171375
TI  - Biogeochemistry in highly reduced mussel farm sediments during macrofaunal
      recolonization by Amphiura filiformis and Nephtys sp.
AB  - Mussel farming is considered a viable means for reducing coastal eutrophication.
      This study assessed the importance of bioturbation by recolonizing fauna for
      benthic solute fluxes and porewater distributions in manipulated mussel farm
      sediments. Three consecutive time-series flux incubations were performed during
      an experimental period of three weeks in sieved farm sediment treated with the
      brittle star Amphiura filiformis and the polychaete Nephtys sp. The functional
      behavior of Nephtys sp. and interactions between Nephtys sp. and the
      spontaneously colonizing spionid Malacoceros fuliginosus determined the
      biogeochemical response in the Nephtys sp. treatment. For example, the oxic zone
      was restricted and benthic nitrate and silicate fluxes were reduced compared to
      the brittle star treatment. A. filiformis seemed to enhance the bioadvective
      solute transport, although an increased supply of oxygen was due to the highly
      reducing conditions of the sediment mainly seen as secondary effects related to
      porewater distributions and benthic nutrient fluxes.

PMID- 19171377
TI  - Expansion and delivery of human fibroblasts on micronized acellular dermal matrix
      for skin regeneration.
AB  - In order to obtain an abundant supply of autologous dermal fibroblasts for the
      manufacture of engineered autologous dermal substitutes, we fabricated the
      micronized acellular dermal matrix (MADM) microcarriers and expanded human
      fibroblasts on them. This novel approach eliminated the need for the repeated
      trypsinizations that may disrupt cell-extracellular matrix interactions and
      impair cell viability. This cell expansion protocol simultaneously formed an
      engineered particulate dermal substitute (EPDS) avoiding cell reseeded on the
      scaffolds process. We further tested its feasibility and effectiveness in athymic
      murine subcutaneous injection and full-thickness cutaneous wound model. Our
      results showed that MADM microcarriers retained the ultrastructure of the
      acellular dermal matrix, had good biocompatibility, and supported human
      fibroblast expansion either as a direct culture substrate or through culturing
      cells in conditioned medium prepared from them. In the animal study, EPDS formed
      a thick layer of tissue below the subcutaneous muscle tissue at 3 weeks following
      EPDS injection into subcutaneous tissue. In full-thickness cutaneous wound, the
      degree of wound healing with EPDS implantation was better than that without EPDS
      although healing rates were not significantly different between wounds implanted
      with or without EPDS. This demonstrates the potential utility of MADM not only as
      a cell culture substrate to expand fibroblasts but also as a cell transplantation
      vehicle for skin regeneration, with several advantages over current expansion
      transplantation protocols for skin regeneration. In addition, EPDS may be used
      for cosmetic or reconstructive soft tissue augmentation in a minimally invasive
      fashion.

PMID- 19171376
TI  - Poly(amidoamine) dendrimer-drug conjugates with disulfide linkages for
      intracellular drug delivery.
AB  - Understanding and improving drug release kinetics from dendrimer-drug conjugates
      are key steps to improve their in vivo efficacy. N-Acetyl cysteine (NAC) is an
      anti-inflammatory agent with significant potential for clinical use in the
      treatment of neuroinflammation, stroke and cerebral palsy. There is a need for
      delivery of NAC which can enhance its efficacy, reduce dosage and prevent it from
      binding plasma proteins. For this purpose, a poly(amidoamine) dendrimer-NAC
      conjugate that contains a disulfide linkage was synthesized and evaluated for its
      release kinetics in the presence of glutathione (GSH), cysteine (Cys), and bovine
      serum albumin (BSA) at both physiological and lysosomal pH. The results indicate
      that the prepared conjugate can deliver approximately 60% of its NAC payload
      within 1h at intracellular GSH concentrations at physiological pH, whereas the
      conjugate did not release any drug at plasma GSH levels. The stability of the
      conjugate in the presence of bovine serum albumin at plasma concentrations was
      also demonstrated. The efficacy of the dendrimer-NAC conjugate was measured in
      activated microglial cells (target cells in vivo) using the reactive oxygen
      species (ROS) assay. The conjugates showed an order of magnitude increase in
      antioxidant activity compared to free drug. When combined with intrinsic and
      ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices
      can lead to improved drug release profiles and in vivo efficacy.

PMID- 19171378
TI  - Inhibition of complement activation on a model biomaterial surface by
      streptococcal M protein-derived peptides.
AB  - The aim of this study was to evaluate a new approach to inhibit complement
      activation triggered by biomaterial surfaces in contact with blood. In order to
      inhibit complement activation initiated by the classical pathway (CP), we used
      streptococcal M protein-derived peptides that specifically bind human C4BP, an
      inhibitor of the CP. The peptides were used to coat polystyrene microtiter wells
      which served as a model biomaterial. The ability of coated peptides to bind C4BP
      and to attenuate complement activation via the CP (monitored as generation of
      fluid-phase C3a and binding of fragments of C3 and C4 to the surface) was
      investigated using diluted normal human serum, where complement activation by the
      AP is minimal, as well as serum from a patient lacking alternative pathway
      activation. Complement activation (all parameters) was significantly decreased in
      serum incubated in well surfaces coated with peptides. Total inhibition of
      complement activation was obtained at peptide coating concentrations as low as 1
      5 microg/mL. Successful use of Streptococcus-derived peptides shows that it is
      feasible to control complement activation at a model biomaterial surface by
      capturing autologous complement regulatory molecules from plasma.

PMID- 19171379
TI  - The long-term consequences of childhood emotional maltreatment on development:
      (mal)adaptation in adolescence and young adulthood.

PMID- 19171380
TI  - Cardio-respiratory function and oxidative stress biomarkers in Nile tilapia
      exposed to the organophosphate insecticide trichlorfon (NEGUVON).
AB  - The cardio-respiratory function, oxidative stress and fish antioxidants were
      analyzed in juvenile Nile tilapia exposed for 96 h to a sublethal trichlorfon
      (TRC-Neguvon, Bayer) concentration of 0.5 mg L(-1). The exposure to TRC induced
      oxidative stress in the heart, as manifested by the glutathione S-transferase
      depletion and hydroperoxide elevation, and was the most sensitive organ when
      compared to the liver and gills, in which the antioxidant mechanisms against TRC
      exposure were sufficient to remove reactive oxygen species (ROS), preventing the
      increase of lipid peroxidation. TRC exposure also reduced O(2) uptake (V O(2))
      and increased the critical oxygen tension (PcO(2)), reducing the species capacity
      to survive prolonged hypoxic conditions. The heart rate and force contraction
      were significantly impaired, making the heart the most sensitive organ when
      exposed to the TRC.

PMID- 19171381
TI  - Assessment of bioaccumulation of heavy metals by different plant species grown on
      fly ash dump.
AB  - A field experiment was conducted on a 10-hectare area on fly ash dump at
      Khaperkheda Thermal Power Plant, Nagpur, India, where different ecologically and
      economically important plant species were planted using bioremediation
      technology. The technology involves the use of organic amendment and selection of
      suitable plant species along with site-specific nitrogen-fixing strains of
      biofertilizers. The study was conducted to find out the metal accumulation
      potential of different plant species. The total heavy metal contents in fly ash
      were determined and their relative abundance was found in the order of
      Fe>Mn>Zn>Cu>Ni>Cr>Pb>Cd. Fly ash samples had acidic pH, low electrical
      conductivity, low level of organic carbon and trace amounts of N and P.
      Plantation of divergent species was done on fly ash dump using the bioremediation
      technique. After 3 years of plantation, luxuriant growth of these species was
      found covering almost the entire fly ash dump. The results of the metal analysis
      of these species indicated that iron accumulated to the greatest extent in
      vegetation followed by Mn, Ni, Zn, Cu, Cr and Pb. Cassia siamea was found to
      accumulate all metals at higher concentrations compared to other species. The
      experimental study revealed that C. siamea could be used as a hyper-accumulator
      plant for bioremediation of fly ash dump.

PMID- 19171382
TI  - Side-on binding of p-sulphonatocalix[4]arene to the dinuclear platinum complex
      trans-[{PtCl(NH3)2}2mu-dpzm]2+ and its implications for anticancer drug delivery.
AB  - The utility of p-sulphonatocalix[4]arene (s-CX[4]) as a drug delivery vehicle for
      multinuclear platinum anticancer agents, using trans-[{PtCl(NH(3))(2)}(2)mu
      dpzm](2+) (di-Pt; where dpzm=4,4'-dipyrazolylmethane) as a model complex, has
      been examined using (1)H nuclear magnetic resonance, electrospray ionisation mass
      spectrometry, molecular modelling and in vitro growth inhibition assays. s-CX[4]
      binds di-Pt in a side-on fashion in a ratio of 1:1, with the dpzm ligand of the
      metal complex located within the s-CX[4] cavity with binding further stabilised
      by ion-ion interactions and hydrogen bonding between the metal complex am(m)ine
      groups and the s-CX[4] sulphate groups. Partial encapsulation of di-Pt within the
      cavity does not prevent binding of 5'-guanosine monophosphate to the metal
      complex. When bound to two individual guanosine molecules, di-Pt also remains
      partially bound by s-CX[4]. The cytotoxicity of free di-Pt and s-CX[4] and their
      host guest complex was examined using in vitro growth inhibition assays in the
      A2780 and A2780cis human ovarian cancer cell lines. Free di-Pt has an IC(50) of
      100 and 60 microM, respectively, in the cell lines, which is significantly less
      active than cisplatin (1.9 and 8.1 microM, respectively). s-CX[4] displays no
      cytotoxicity at concentrations up to 1.5mM and does not affect the cytotoxicity
      of di-Pt, probably because its low binding constant to the metal complex (6.8 x
      10(4)M(-1)) means the host-guest complex is mostly disassociated at biologically
      relevant concentrations.

PMID- 19171383
TI  - Dinuclear copper(II) complexes containing 6-(benzylamino)purines as bridging
      ligands: synthesis, characterization, and in vitro and in vivo antioxidant
      activities.
AB  - A series of dinuclear copper(II) complexes involving 6-(benzylamino)purine
      derivatives, (HL(n)), as bridging ligands were synthesized, characterized and
      tested for both their in vitro and in vivo antioxidant activities. Based on
      results of elemental analyses, temperature dependence of magnetic susceptibility
      measurements, UV-vis, FTIR, EPR, NMR and MALDI-TOF mass spectroscopy,
      conductivity measurements and thermal analyses, the complexes with general
      compositions of [Cu(2)(mu-HL(n))(4)Cl(2)]Cl(2).2H(2)O (1-4) and [Cu(2)(mu
      HL(n))(2)(mu-Cl)(2)Cl(2)] (5-7) were prepared {where n=1-4; HL(1)=6-[(2
      methoxybenzyl)amino]purine, HL(2)=6-[(4-methoxybenzyl)amino]purine, HL(3)=6-[(2,3
      dimethoxybenzyl)amino]purine and HL(4)=6-[(3,4-dimethoxybenzyl)amino]purine}. In
      the case of complexes 2, 3, 5 and 7, the antioxidant activities were studied by
      both in vitro {superoxide dismutase-mimic (SOD-mimic) activity} and in vivo
      {cytoprotective effect against the alloxan-induced diabetes (antidiabetic
      activity)} methods. The obtained IC(50) value of the SOD-mimic activity for the
      complex 5 (IC(50)=0.253 microM) was shown to be even better than that of the
      native bovine Cu,Zn-SOD enzyme (IC(50)=0.480 microM), used as a standard. As for
      the antidiabetic activity, the pretreatment of mice with complexes 3 and 7 led to
      the complete elimination of cytotoxic attack of alloxan and its free radical
      metabolites, used as a diabetogenic agent. The cytoprotective effect of these
      compounds was proved by the preservation of the initial blood glucose levels of
      the pretreated animals, as against the untreated control group.

PMID- 19171384
TI  - Efficacy, safety and tolerability of quetiapine augmentation in treatment
      resistant depression: an open-label, pilot study.
AB  - BACKGROUND: Atypical antipsychotics may have efficacy as augmentation therapy in
      treatment resistant depression (TRD) but evidence is limited. METHODS: An open
      label study of quetiapine augmentation in 24 patients (mean age: 46.3 years) with
      a DSM-IV major depressive episode resistant to at least 2 trials of
      antidepressant medication, and currently taking a monoamine reuptake inhibitor.
      An 8-week treatment phase was followed by an 18-week extension in patients who
      showed clinical benefit. RESULTS: Eighteen patients (75%) completed the 8-week
      treatment phase with seven patients (29%) being responders on the Montgomery
      Asberg Depression Rating Scale and 13 (54%) on the CGI-I. Fewer patients
      responded if they had previously received olanzapine in the current episode but
      this was not statistically significant (0% v 37%, p=0.27). Of the eleven patients
      entering the extension phase, 3 patients (27%) experienced a significant
      worsening of mood. The most common adverse events were sedation (54%), dry mouth
      (38%) and dizziness (29%). Significant weight gain was found in 40% of patients
      treated for 26 weeks. Average quetiapine doses were 245 mg at 8 weeks and 346 mg
      at 26 weeks. CONCLUSIONS: Quetiapine may be a helpful adjunctive agent for some
      patients with TRD but placebo-controlled trials are needed to establish its place
      in management. LIMITATIONS: The trial was open-label and the numbers were small.

PMID- 19171385
TI  - Interferon alpha and neuromuscular disorders.
AB  - Interferon-alpha (IFNalpha) is a potent extracellular protein mediator of host
      defense and homeostasis. IFNalpha has well-established direct antiviral,
      antiproliferative and immunomodulatory properties. The worldwide, increasing and
      long-term use of IFNalpha, particularly for the treatment of chronic hepatitis C
      virus infection, has drawn attention to the development or exacerbation of
      numerous autoimmune phenomena, including a variety of neuropathy syndromes,
      neuromuscular junction disorders and myopathies. Management entailed withdrawal
      of IFNalpha therapy with supportive, immunomodulatory, and symptomatic treatment
      as clinically indicated. The mechanisms of IFNalpha-induced autoimmunity are
      incompletely understood, and likely vary depending on the inherent differences in
      the pathogenesis of the immune disorder on a background of patient genetic
      susceptibility. In addition, there is preliminary evidence from case reports and
      open-label studies that the immunomodulatory effects of IFNalpha may have
      potential as a treatment option for a spectrum of immune-mediated neuromuscular
      diseases, but further studies are needed.

PMID- 19171386
TI  - Cannabis induced acute coronary syndrome in a young female.
AB  - Nowadays cannabis is the most common substance of drug abuse and
      pathophysiological effects have been described on the cardiovascular system. Yet
      there is limited information concerning cannabis induced acute coronary syndrome
      and the exact contribution of cannabis smoking to coronary artery disease and its
      mechanism are not known. We describe a case of acute coronary syndrome following
      cannabis smoking in a young female with no predisposing causes for thrombosis.

PMID- 19171387
TI  - Low birth weight and increased cardiovascular risk: fetal programming.

PMID- 19171388
TI  - Combination of sitaxentan and tadalafil for idiopathic pulmonary arterial
      hypertension following relapse on bosentan.
AB  - Sitaxentan, a highly-selective endothelin receptor antagonist (ETRA) and bosentan
      a non-selective ETRA are both approved for the treatment of idiopathic pulmonary
      arterial hypertension (iPAH). Sildenafil is a phosphodiesterase-5 (PDE-5)
      inhibitor used in the treatment of iPAH. Tadalafil is a long acting PDE-5
      inhibitor largely unexplored for the treatment of iPAH. Following failure of
      monotherapy combination therapy with an ETRA and a PDE-5 inhibitor is often used,
      a frequently used combination being bosentan with sildenafil. We report our
      clinical experience in three patients with iPAH treated with a combination of
      sitaxentan and tadalafil, who previously discontinued bosentan. There was
      sustained symptomatic and haemodynamic improvement in all three patients treated
      with the combination. No adverse effect related to the combination treatment was
      noted. Sitaxentan and tadalafil, both being once a day treatments, can also
      possibly increase compliance.

PMID- 19171389
TI  - Anomalous right coronary artery arising next to the left coronary ostium:
      unambiguous detection of the anatomy by computed tomography and evaluation of
      functional significance by cardiovascular magnetic resonance.
AB  - Herein we report on the diagnostic potential of multi-detector row computed
      tomography (MDCT) combined with cardiovascular magnetic resonance (CMR) for the
      diagnostic workup in an adult patient with a rare coronary anomaly. MDCT
      unambiguously detected the anomalous right coronary artery (RCA), which
      originated next to the left coronary ostium and coursed inter-arterially between
      the ascending aorta and the pulmonary trunk. The intramural proximal
      intussusception of the ectopic RCA could be clearly appreciated on MDCT images,
      while multiple mixed plaques were detected in the left anterior descending (LAD),
      resulting in moderate stenosis of this vessel. CMR during adenosine infusion
      ruled-out inducible ischemia, yielding normal perfusion patterns both in the RCA
      and in the LAD coronary territory. Since ischemia was not demonstrated by stress
      CMR, revascularization was not performed.

PMID- 19171390
TI  - Stenotrophomonas maltophilia pacemaker endocarditis in a patient with d
      transposition of the great arteries after atrial switch procedure.
AB  - We report a case of pacemaker endocarditis due to Stenotrophomonas maltophilia in
      a 22-year-old Caucasian man with d-transposition of the great arteries after
      atrial switch procedure. S.maltophilia isolated from blood cultures was
      susceptible to trimethoprim-sulfamethoxazole and amikacin, and resistant to
      ciprofloxacin and all tested beta-lactam antibiotics. The infected pacemaker
      system was completely removed by thoracotomy. Simultaneously, a new DDD pacemaker
      and epicardial electrodes were successfully implanted and selective antibiotic
      therapy consisting of trimethoprim-sulfamethoxazole (480 mg i.v. q 6 h) and
      amikacin (250 mg i.v. twice daily) was continued. However, the post-operative
      course was complicated by septic shock and the patient died on 9th day after
      surgery. Importantly, S.maltophilia isolated from extracted pacemaker leads was
      multidrug-resistant including to trimethoprim-sulfamethoxazole, ciprofloxacin,
      all tested aminoglycosides, and beta-lactams, with the exception of ticarcillin
      clavulanate. In conclusion, pacemaker endocarditis due to Stenotrophomonas
      maltophilia is an extremely rare but serious complication of permanent pacing
      therapy. The susceptibility of S.maltophilia isolates to antimicrobial agents can
      change during the course of infection. Despite the inherent resistance of
      S.maltophilia to most beta-lactam antibiotics, multidrug-resistant strains may be
      susceptible in vitro to ticarcillin-clavulanate. Further studies are needed to
      determine the optimal management of patients with pacemaker endocarditis caused
      by Stenotrophomonas maltophilia.

PMID- 19171391
TI  - Decreased circulatory erythropoietin in hyperacute phase of myocardial ischemia.
AB  - PURPOSE: Erythropoietin provides cellular protection by inhibiting apoptosis.
      Myocardial damage related to the cardiac ischemia is more prominent especially in
      the first 6 h. In the present study, circulatory erythropoietin levels in
      response to cardiac ischemia were evaluated. MATERIALS AND METHODS: Patients with
      stable angina who underwent balloon angioplasty (study group, n = 55) and
      hospitalized for coronary angiography (as control group, n = 23) were enrolled
      into the study. Serum erythropoietin levels were measured in both groups in
      baseline, 6 and 18 h after the procedure. RESULTS: Coronary balloon inflation
      time was accepted as duration of myocardial ischemia. Study group showed
      significant erythropoietin reduction at sixth hour compared to control group.
      Erythropoietin reduction at sixth hour was significantly correlated with duration
      of myocardial ischemia. CONCLUSION: Decreased circulatory erythropoietin levels
      in the early phase of acute cardiac ischemia may accelerate the apoptotic
      activity. Recombinant erythropoietin replacement to prevent erythropoietin
      decrease following cardiac ischemia may have negative effect on myocyte loss.

PMID- 19171392
TI  - Myocardial stunning identified by using strain/strain rate imaging during
      dobutamine stress echocardiography in a rare late recurrence of Tako-Tsubo
      syndrome.
AB  - Tako-Tsubo cardiomyopathy affects postmenopausal women and is often associated to
      emotional or physical stress. It is typically characterized by transient left
      ventricular apical ballooning with chest pain and, electrocardiographic changes
      and biochemical markers suggestive of acute coronary syndrome, despite
      angiographically normal coronary arteriograms. The pathogenesis of the condition
      is still unknown, but increased catecholamine levels have been postulated as a
      pathogenic mechanism. Little data exist in the medical literature regarding
      recurrent events in this disorder. We present here a case of a 62 year-old woman
      who had a recurrent episode of Tako-Tsubo syndrome 6 years after initial
      presentation with typical features of the condition. An underlying cause could
      not be found that could explain the recurrence of this late episode.

PMID- 19171393
TI  - Incidence of diffuse and focal chronic stent recoil after implantation of current
      generation bare-metal and drug-eluting stents.

PMID- 19171394
TI  - Changing axis deviation and paroxysmal atrial flutter associated with subclinical
      hyperthyroidism.
AB  - Subclinical hyperthyroidism is an increasingly recognized entity that is defined
      as a normal serum free thyroxine and free triiodothyronine levels with a thyroid
      stimulating hormone level suppressed below the normal range and usually
      undetectable. It has been reported that subclinical hyperthyroidism is not
      associated with coronary heart disease or mortality from cardiovascular causes
      but it is sufficient to induce arrhythmias including atrial fibrillation and
      atrial flutter. It has also been reported that increased factor X activity in
      patients with subclinical hyperthyroidism represents a potential hypercoagulable
      state. Rarely, it has also been reported intermittent changing axis deviation
      during atrial fibrillation and during atrial flutter. We present a case of
      paroxysmal atrial flutter and changing axis deviation associated with subclinical
      hyperthyroidism, in a 76-year-old Italian man. Also this case focuses attention
      on the importance of a correct evaluation of subclinical hyperthyroidism.

PMID- 19171395
TI  - Recurrence of cerebrovascular events in young adults with a secundum atrial
      septal defect.
AB  - BACKGROUND: The recurrence rate for cerebrovascular ischemic events in patients
      after a first TIA or CVA with an atrial septal defect type 2 (ASD2) remains
      unknown. At present, there are no guidelines with respect to appropriate
      treatment. The aim of this study was to determine incidence rates of recurrent
      cerebrovascular events in patients with ASD2. METHODS: A multicenter,
      retrospective study was performed at selected centres in The Netherlands, United
      Kingdom and United States. All patients with ASD2 and a prior cerebrovascular
      event were identified from available databases. Clinical data were retrieved from
      medical files, electronic databases and radiographic charts. RESULTS: Fifty-six
      adult patients born between 1950 and 1990 (median age at first cerebrovascular
      event 37.5, range 15-53 years) were recruited. Recurrent events (9 TIA, 2 CVA)
      were recorded in 11 patients (19.6%) during a median follow-up time of 5.3 years
      (range 0.2-28.9). Non-closure of the defect was the only significant predictor of
      a recurrent event (p=0.01). CONCLUSION: Patients with an ASD2 and a history of a
      cerebrovascular ischemic event have a substantial risk for recurrent events.
      Closure of the ASD2 seems to substantially decrease the risk of recurrence.
      However, prospective randomized trials are needed to confirm our findings.

PMID- 19171396
TI  - Recurrent bare metal stent thrombosis: six years, single center experience.
AB  - PURPOSE: To evaluate clinical characteristics, treatment and outcomes of patients
      suffering from recurrent bare metal stent thrombosis (RST). METHODS: A
      retrospective evaluation of patients who underwent percutaneous coronary
      intervention (PCI) with bare metal stent implantation between January 2002 and
      December 2007 was performed. Patients who experienced more than one in stent
      thrombotic episode were identified and procedural and clinical outcomes were
      investigated. RESULTS: Eight thousand eight hundred sixteen patients underwent
      PCI with bare metal stent implantation during the study period. Ninety five
      patients (1.1%) underwent PCI due to stent thrombosis and 6 (6.3%) of them [mean
      age 69 +/- 14 years (range 43-83 years)] underwent a second procedure due to RST.
      Emergency PCI was performed in all patients, with a favourable angiographic
      outcome in 4 (67%) of them. The procedure was complicated by death in 1, major
      ischemic stroke in 1 and acute coronary by pass grafting in 1 patient. The
      ejection fraction before the initial intervention and after the second thrombotic
      episode declined from 52 +/- 14% to 33 +/- 15% (p < 0.05). CONCLUSION: Recurrent
      stent thrombosis is a rare, but major complication following stent implantation,
      which dramatically affects patients' outcomes.

PMID- 19171397
TI  - Possible explanation for no evidence of carditis in human H5N1 infection.

PMID- 19171398
TI  - Determinants of left main calcifications in a cohort of 2136 diabetes patients.
AB  - INTRODUCTION: Left main (LM) calcification has been shown to be an independent
      predictor of mortality. Diabetes accelerates atherosclerosis and coronary artery
      calcification (CAC). In this study we aimed to describe the predictors of LM
      calcification in diabetes patients. METHODS: From a database of >25,000 patients
      who have undergone CAC scanning at our institution, consecutive diabetic patients
      (n=2136) were evaluated for demographic data, CAC scores and coronary risk
      factors. RESULTS: In our cohort 29.1% of patients had LM CAC. Of the classical
      atherosclerosis risk factors, in binary regression analysis, only age (OR 1.03
      [1.017-1.043]), male gender (OR 1.59; p<0.05), hypertension (OR 1.73; p<0.05),
      and CAC score (OR 1.001; p<0.05) were found to be independently associated with
      LM disease. CONCLUSION: The prevalence of LM CAC is high amongst diabetics
      (29.1%); associated with increased age, HTN and male sex.

PMID- 19171399
TI  - Assessment of myocardial scarring by contrast enhanced magnetic resonance imaging
      in a patient 11 years after percutaneous transluminal septal myocardial ablation
      in hypertrophic obstructive cardiomyopathy.
AB  - We report on a 60 year-old male who was one of the first patients who underwent
      percutaneous transluminal septal myocardial ablation (PTSMA) in our institution
      in 1996. Contrast enhanced cardiac magnetic resonance imaging (MRI) 11 years
      after the PTSMA demonstrated extensive scarring, in septal and inferior segments
      of the left ventricle, and an excellent functional result. It has been previously
      demonstrated that contrast-enhanced MRI allows detailed evaluation of size and
      location of septal myocardial infarction induced by PTSMA, and that infarction
      size detected by MRI correlates well with clinical indexes of infarct size. Our
      case report underlines the importance of ongoing specialized care and
      reassessment of patients after PTSMA including continuous clinical risk
      assessment.

PMID- 19171400
TI  - The paradox of high apolipoprotein A-I levels independently predicting incident
      type-2 diabetes among Turks.
AB  - BACKGROUND: Predictive value of apolipoprotein (apo) A-I for incident
      hypertension, metabolic syndrome (MetS), type 2 diabetes (DM) and coronary heart
      disease (CHD) needs further exploration. METHODS: A representative sample of
      Turkish adults was studied with this purpose prospectively. Sex-specific apoA-I
      tertiles were examined regarding cardiometabolic risk. RESULTS AND CONCLUSIONS: A
      total of 1044 men and 1067 women (aged 49+/-12 years at baseline) were followed
      up over 7.4 years. High serum apoA-I levels were significantly associated in
      multivariable analysis with female sex, aging, alcohol intake, (inversely)
      cigarette smoking and, in women, with systolic blood pressure. Risk of diabetes
      was predicted in logistic regression in both genders by top versus bottom apoA-I
      tertile (RR 1.98; [95%CI 1.31; 3.0]), additive to age, body mass index (BMI), C
      reactive protein (CRP), HDL-cholesterol and lipid lowering drugs. By adding sex
      hormone-binding globulin to the model in a subset of the sample, the association
      between high apoA-I and incident diabetes was attenuated only in women. ApoA-I
      tertiles tended to be positively associated also with hypertension and CHD only
      in women but this did not reach significance. High compared with low serum apoA-I
      levels nearly double the risk for incident diabetes, additively to age, BMI, CRP,
      HDL-cholesterol among Turks. Systemic inflammation concomitant with prevailing
      MetS might turn apoA-I into proinflammatory particles.

PMID- 19171401
TI  - Atrial fibrillation associated with chocolate intake abuse and chronic salbutamol
      inhalation abuse.
AB  - The use of substances as the substrate for atrial fibrillation is not frequently
      recognized. Chocolate is derived from the roasted seeds of the plant theobroma
      cacao and its components are the methylxanthine alkaloids theobromine and
      caffeine. Caffeine is a methylxanthine whose primary biological effect is the
      competitive antagonism of the adenosine receptor. Normal consumption of caffeine
      was not associated with risk of atrial fibrillation or flutter. Sympathomimetic
      effects, due to circulating catecholamines cause the cardiac manifestations of
      caffeine overdose toxicity, produce tachyarrhythmias such as supraventricular
      tachycardia, atrial fibrillation, ventricular tachycardia, and ventricular
      fibrillation.The commonly used doses of inhaled or nebulized salbutamol induced
      no acute myocardial ischaemia, arrhythmias or changes in heart rate variability
      in patients with coronary artery disease and clinically stable asthma or chronic
      obstructive pulmonary disease. Two-week salbutamol treatment shifts the
      cardiovascular autonomic regulation to a new level characterized by greater
      sympathetic responsiveness and slight beta2-receptor tolerance. We present a case
      of atrial fibrillation associated with chocolate intake abuse in a 19-year-old
      Italian woman with chronic salbutamol inhalation abuse. This case focuses
      attention on chocolate intake abuse associated with chronic salbutamol abuse as
      the substrate for atrial fibrillation.

PMID- 19171402
TI  - Peripartum cardiomyopathy in the era of cardiac magnetic resonance imaging: first
      results and perspectives.

PMID- 19171403
TI  - Risk of cerebrovascular events after neck and supraclavicular radiotherapy: a
      systematic review.
AB  - OBJECTIVE: Although low dose radiation therapy (RT) has been used to prevent re
      occlusion of coronary arteries, it may also precipitate vascular damage.
      Specifically, irradiation to the neck is related to subsequent vascular wall
      thickening and atherosclerotic plaque formation. Several investigators, reporting
      patients with varied disease processes and using different methods, have
      described an increased risk of cerebrovascular events (CVEs) after RT to the neck
      for head and neck cancer, breast cancer, or lymphoma. Our purpose is to determine
      the rate and risk of CVEs in patients after receiving radiation therapy to the
      neck. METHODS: We performed a pooled analysis of the published data to document
      the cumulative risk of subsequent stroke after RT to the neck. An extensive
      MEDLINE and PUBMED search yielded five articles involving 6908 patients
      describing institutional series or cohort analyses comparing the frequency of CVE
      in irradiated versus non-irradiated patients. RESULTS: Sixty-six CVEs were
      reported in 2567 patients after neck RT, whereas only 12 CVEs were documented in
      4119 non-irradiated patients. Crude risk of CVEs after neck RT was 2.6%, and was
      0.29% in non-irradiated patients. This odds ratio of 9.0 was statistically
      significant (95% CI 4.9, 16.7; p<0.0001). Data for supraclavicular RT were more
      difficult to analyze given differences in populations and reporting between the
      three studies, but it appears a significant risk is unlikely. CONCLUSIONS: Neck
      RT increases the likelihood of CVEs, but this risk must be reconciled with the
      benefits of the therapy in the specific clinical situation. For instance,
      consideration should be made to limiting neck RT where possible for breast cancer
      and lymphoma patients.

PMID- 19171404
TI  - Quantitative risk assessment: is more complex always better? Simple is not stupid
      and complex is not always more correct.
AB  - In quantitative risk assessments a large variety of complexities can be found,
      from simple and deterministic to very extensive and stochastic. This publication
      advocates that both simple and complex approaches have their value and should be
      done in parallel. The simple analysis gives much insight and can help to detect
      main factors and potential errors in the complex analysis. Extensive analysis
      with increased complexity suggests better precision but might not increase the
      accuracy, due to the uncertainty in the additional parameters. However, complex
      analysis supplies more confidence in certain phenomena and might also increase
      insight. This is shown with two examples. The first is the effectiveness of
      sampling plans for powdered infant formula, for factories operating at various
      levels of contamination. The results of a simple determination, an analysis
      including a within batch variability and an analysis including both within batch
      and between batch variability will be compared. The last approach has as
      advantage that apart from determining the probability of rejection of a batch, it
      can determine also the reduction of the health risk in the population following a
      certain sampling plan; it is more complex but it also does bring additional
      information. However the conclusions still contain large uncertainty, due to the
      difficulty of obtaining realistic values of the within batch and between batch
      variability. The second example is dose-response relations comparing the
      exponential model (one parameter), the beta-Poisson model (two parameters) and
      the Weibull-gamma model (three parameters). The conclusion is not that simple is
      best, but that simple is not stupid, and provides valuable information. Complex,
      on the other hand, is not always by definition more correct, but also does have
      its merits.

PMID- 19171405
TI  - The RNA infrastructure: dark matter of the eukaryotic cell?
AB  - Eukaryotes express many functional non-protein-coding RNAs (ncRNAs) that
      participate in the processing and regulation of other RNA molecules. By focusing
      on connections between RNA-based processes, common patterns emerge that form a
      network-like RNA infrastructure. Owing to the intracellular movement of RNA
      during its processing (both between nuclear compartments and between the nucleus
      and cytoplasm), the RNA infrastructure contains both spatial and temporal
      connections. As research moves away from being protein-centric and focuses more
      on genomics, it is timely to explore these often 'hidden' aspects of the
      eukaryotic cell. The general and ancestral nature of most basic RNA-processing
      steps places a new focus on the generality of the spatial and temporal steps in
      RNA processing.

PMID- 19171406
TI  - Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy
      chain (CD98) expression in stage I pulmonary adenocarcinoma.
AB  - BACKGROUND: The purpose of this study was to evaluate the prognostic value of l
      type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in
      patients with stage I pulmonary adenocarcinoma. METHODS: A total of 139
      consecutive patients with pathologic stage I pulmonary adenocarcinoma were
      retrospectively reviewed. Expression of LAT1, CD98, Ki-67 labeling index,
      vascular endothelial growth factor (VEGF) and microvessel density (MVD) was also
      evaluated immunohistochemically and correlated with the prognosis of patients
      after complete resection of the tumor. RESULTS: LAT1 and CD98 expression were
      positive in 23% (32/139) and 22% (31/139), respectively (p=0.887). LAT1 with CD98
      expression was recognized in 15% (21/139). LAT1 expression was significantly
      correlated with CD98, Ki-67 labeling index, VEGF, and MVD. The 5-year survival
      rates of LAT1-positive and -negative patients and CD98-positive and -negative
      patients, were 60.2 and 95.2% (p<0.0001) and 72.5 and 93.4% (p=0.0008),
      respectively. Univariate analysis disclosed that cellular proliferation and MVD
      in the tumor were significant prognostic factors. However, multivariate analysis
      confirmed that positive expression of LAT1 and CD98 was an independent factor for
      predicting a poor prognosis. CONCLUSION: The overexpression of LAT1 and CD98 is a
      pathological factor to predict the prognosis in patients with resectable stage I
      pulmonary adenocarcinoma.

PMID- 19171407
TI  - Dose intensity correlate with survival in elderly patients treated with
      chemotherapy for advanced non-small cell lung cancer.
AB  - INTRODUCTION: In elderly patients treated with chemotherapy for advanced non
      small cell lung cancer (NSCLC), frequently an adequate dose intensity (DI) is
      difficult to be delivered. We therefore performed in this population a study to
      assess the delivered DI and its impact on clinical outcome. PATIENTS AND METHODS:
      Inclusion criteria were: age equal or greater than 70 years; cytological or
      histological diagnosis of NSCLC; stage IIIB or IV; no previous chemotherapy for
      advanced disease. Total relative dose intensity (RDI) was taken into account for
      the analysis. An RDI less than 80% was considered as suboptimal for tumor
      shrinkage. A survival comparison between subgroups (more or less than 80% RDI)
      was done. RESULTS: 107 patients were eligible for the analysis. Mean age was 74.3
      years. PS was 0-1 in 92.5% of subjects. Mean number of comorbidities was 1.86.
      The most frequently chemotherapy regimens used were single agent vinorelbine and
      single agent gemcitabine. Overall mean RDI was 68%; 36% of patients received a
      RDI>80% of the originally planned one. The objective response rate (RR) was 55.2%
      and 33.3% respectively for patients receiving more or less than 80% of the RDI
      (p<0.01); a significant difference in overall survival between these two groups
      (p<0.0001) was also recorded. Baseline hemoglobin and body mass index (BMI) were
      the variables that significantly influenced the delivered RDI. CONCLUSIONS: These
      data suggest that in elderly patients treated with chemotherapy for advanced
      NSCLC an adequate dose intensity has a significant positive impact on both
      response rate and overall survival.

PMID- 19171408
TI  - Anti-metastatic potential of Punarnavine, an alkaloid from Boerhaavia diffusa
      Linn.
AB  - The alkaloid Punarnavine isolated from the plant Boerhaavia diffusa Linn. was
      studied for its anti-metastatic activity using B16F-10 melanoma cells in C57BL/6
      mice. Administration of Punarnavine (40mg/kg body weight) prophylactically
      (95.25%), simultaneously (93.9%) and 10 days after tumor inoculation (80.1%)
      could inhibit the metastatic colony formation of melanoma in lungs. Survival rate
      of the metastatic tumor-bearing animals were increased significantly by the
      administration of Punarnavine in all the modalities compared to the metastasis
      bearing untreated control. These results correlated with the biochemical
      parameters such as lung collagen hydroxyl proline, uronic acid, hexosamine, serum
      sialic acid, serum gamma-glutamyltranspeptidase and serum vascular endothelial
      growth factor (VEGF) levels and histopathological studies. Punarnavine
      administration could suppress or down regulate the expression of MMP-2, MMP-9
      (MMP--matrix metalloproteinase), ERK-1, ERK-2 (ERK--extracellular-signal
      regulated kinase) and VEGF in the lung tissue of metastasis-induced animals.
      Punarnavine could inhibit MMP-2 and MMP-9 protein expression in gelatin
      zymographic analysis of B16F-10 cells. These results indicate Punarnavine could
      inhibit the metastatic progression of B16F-10 melanoma cells in mice.

PMID- 19171409
TI  - Synthesis and evaluation of a novel series of heterocyclic oleanolic acid
      derivatives with anti-osteoclast formation activity.
AB  - Oleanolic acid with anti-bone resorption effect was an active component
      discovered in a medicinal plant of Achyranthes bidentata. A series of
      heterocyclic derivatives of oleanolic acid including indole, pyrazine,
      quinoxaline, quinoline moieties and their natural amino acid amides were
      synthesized. Their inhibitory activity on the formation of osteoclast-like
      multinucleated cells (OCLs) and cytotoxicity of the selected derivatives were
      evaluated. Among the derivatives, compounds 2a and 8a displayed quite a potent
      activity even at 200 nM. The structure-activity relationships of the derivatives
      were also discussed.

PMID- 19171410
TI  - Synthesis and blood glucose lowering effect of novel pyridazinone substituted
      benzenesulfonylurea derivatives.
AB  - Fifteen novel pyridazinone substituted benzenesulfonylurea derivatives (3a-o)
      were synthesized from corresponding sulfonamides derivatives via novel carbamates
      (2a-e). These were characterized by elemental analysis and various spectroscopic
      methods viz. IR, (1)H NMR, (13)C NMR and MS. Blood sugar lowering effect of
      thirteen (3a-c, 3e, 3g-o) sulfonylurea derivatives at the dose of 20 mg/kg (p.o.)
      were assessed using glucose tolerance test in normal and NIDDM (n2-STZ) rat
      models. All compounds except 3c, 3e and 3o almost completely prevented the rise
      of blood glucose of NIDDM rats as compared with NIDDM control. While compounds 3c
      and 3o showed more than 50% prevention in the rise of blood glucose levels. In
      glucose-fed normal rats these compounds at the same dose except 3e significantly
      prevented the rise of blood glucose (more than 50%) when compared with control of
      glucose-fed normal rats. From the results, novel compounds (3a-c, 3g-n) exhibited
      considerably potent blood glucose lowering activity and may be used as lead
      compounds for developing new antidiabetic drugs. Some structure-activity
      relationship was observed while varying nature of 'Ar' and 'R'.

PMID- 19171411
TI  - The effectiveness of the lecturer practitioner role in clinical practice: an
      Irish perspective.
AB  - BACKGROUND: Demands within academia such as teaching, publishing, research
      activity and generating grant income can make it difficult for nurse educators to
      protect time for clinical practice. In an effort to overcome this problem
      lecturer practitioner posts have been introduced with designated responsibilities
      in both clinical and educational settings. METHODS: Using a mixed method
      descriptive methodology student nurses and registered nurses completed a modified
      questionnaire to examine the impact of lecturer practitioners (LPs) in clinical
      practice. Focus groups were also conducted with lecturer practitioners
      themselves. RESULTS: The results identified that by having a clinical remit, LPs
      forged good relationships with student nurses and registered nurses in clinical
      practice, who considered the LP as being a learning resource with realistic
      expectations of the clinical environment. DISCUSSION: The results provide further
      evidence to support the continuation of nurse educators in clinical practice for
      their own development, their students and registered nurses.

PMID- 19171412
TI  - A quantitative pilot study evaluating the effectiveness of a venepuncture and
      cannulation study day.
AB  - Continuing education for nurses is an expensive commodity. In order to justify
      its expense employers must experience tangible benefits to nursing practice. This
      paper describes a quantitative study carried out in an in-service training
      organisation in Northern Ireland. The aim of this study was to pilot a tool,
      which considered factors associated with successful completion of the record of
      practice documentation following training in peripheral intravenous cannulation.
      The questionnaire was sent to all course participants for a single year (n=344).
      The response rate of was 28% (n=97). Seventy two percent of nurses successfully
      cannulated on at least five occasions with most completing the record of practice
      form within one month. There were no significant differences found between
      nursing grades in relation to the time taken to complete the record of practice
      document (p=0.395, Kruskal-Wallis, chi(2)=1.860, df=2). There was highly
      statistically significant correlation found in relation to highest academic grade
      and the time taken to complete the record of practice (p<0.001, r=0.121) as
      illustrated in Fig. 3. However, the strength of the relationship was weak as the
      two variables only shared 1.4% of their variation in common. The difference
      between the grades achieved by hospital and community nurses in time taken to
      complete the record of practice was statistically significant (p=0.003, Mann
      Whitney U=470.000, Z=-3.023) with hospital nurses more likely to complete their
      supervised practice and to do so more quickly.

PMID- 19171414
TI  - Nutrient transport through a Vegetative Filter Strip with subsurface drainage.
AB  - The transport of nutrients and soil sediments in runoff has been recognized as a
      noteworthy environmental issue. Vegetative Filter Strips (VFS) have been used as
      one of the best management practices (BMPs) for retaining nutrients and sediments
      from surface runoff, thus preventing the pollutants from reaching receiving
      waters. However, the effectiveness of a VFS when combined with a subsurface
      drainage system has not been investigated previously. This study was undertaken
      to monitor the retention and transport of nutrients within a VFS that had a
      subsurface drainage system installed at a depth of 1.2 m below the soil surface.
      Nutrient concentrations of NO(3)-N (Nitrate Nitrogen), PO(-)(4)
      (Orthophosphorus), and TP (Total Phosphorus) were measured in surface water
      samples (entering and leaving the VFS), and subsurface outflow. Soil samples were
      collected and analyzed for plant available Phosphorus (Bray P1) and NO(3)-N
      concentrations. Results showed that PO(-)(4), NO(3)-N, and TP concentrations
      decreased in surface flow through the VFS. Many surface outflow water samples
      from the VFS showed concentration reductions of as much as 75% for PO(-)(4) and
      70% for TP. For subsurface outflow water samples through the drainage system,
      concentrations of PO(-)(4) and TP decreased but NO(3)-N concentrations increased
      in comparison to concentrations in surface inflow samples. Soil samples that were
      collected from various depths in the VFS showed a minimal buildup of nutrients in
      the top soil profile but indicated a gradual buildup of nutrients at the depth of
      the subsurface drain. Results demonstrate that although a VFS can be very
      effective in reducing runoff and nutrients from surface flow, the presence of a
      subsurface drain underneath the VFS may not be environmentally beneficial. Such a
      combination may increase NO(3)-N transport from the VFS, thus invalidating the
      purpose of the BMP.

PMID- 19171413
TI  - Modelling phytoremediation by the hyperaccumulating fern, Pteris vittata, of
      soils historically contaminated with arsenic.
AB  - Pteris vittata plants were grown on twenty-one UK soils contaminated with arsenic
      (As) from a wide range of natural and anthropogenic sources. Arsenic
      concentration was measured in fern fronds, soil and soil pore water collected
      with Rhizon samplers. Isotopically exchangeable soil arsenate was determined by
      equilibration with (73)As(V). Removal of As from the 21 soils by three sequential
      crops of P. vittata ranged between 0.1 and 13% of total soil As. Ferns grown on a
      soil subjected to long-term sewage sludge application showed reduced uptake of As
      because of high available phosphate concentrations. A combined solubility-uptake
      model was parameterised to enable prediction of phytoremediation success from
      estimates of soil As, 'As-lability' and soil pH. The model was used to
      demonstrate the remediation potential of P. vittata under different soil
      conditions and with contrasting assumptions regarding re-supply of the labile As
      pool from unavailable forms.

PMID- 19171415
TI  - Reliability of 2D ultrasound measurements of testis size in dolphins taken under
      voluntary behavior.
AB  - This study was undertaken to evaluate the reliability of two-dimensional (2D)
      ultrasound in measuring testis size in dolphins, in vivo, with the subject
      presenting for examination under voluntary or trained behaviour. The testes of
      five bottlenose dolphins (Tursiops aduncus) were measured once by two operators
      to test inter-operator variability (reproducibility) and repeatedly measured by
      the same operator to test intra-operator variability (repeatability). Ultrasound
      examinations for each test were conducted on the same day to avoid measurement
      variability due to time difference. The evaluation of reproducibility and
      repeatability were conducted on separate days. In the ultrasound examination, the
      length, circumference, depth and width of both testes of the animal were
      measured. To prevent bias, measurements were not communicated between the
      operators on-site and repeated measurements were masked. Results showed that both
      reproducibility and repeatability of all the testis measurements were high
      (>90%). Overall, measurement variability of the technique was found to be of a
      satisfactory level. Ultrasound is a useful imaging tool for routine long-term
      monitoring of the testes in this species of animals. Sources of error due to
      movements as a result of the subject being in the water during examinations were
      inevitable and must be taken into account.

PMID- 19171416
TI  - The destruction of Escherichia coli biofilms using high-intensity focused
      ultrasound.
AB  - High-intensity focused ultrasound (HIFU) has shown great potential for replacing
      surgery in many applications. In this work, HIFU was used to destroy Escherichia
      coli (E. coli) biofilms that had been grown on chambered microscope slides.
      Biofilms are central to the pathogenesis and persistence of nosocomial (hospital
      acquired) infections associated with indwelling medical devices. The slides were
      exposed to 9.1 mus pulses at a pulse repetition frequency of 1000 Hz. The pulses
      were generated by a 1.1 MHz spherically focused source with a focal length of 6.3
      cm and an active diameter of 7 cm. The peak rarefactional pressure for the pulses
      was varied as 3.1, 4.1, 5.2, 6.2 and 7.6 MPa in addition to a sham where the
      biofilms were not exposed. The effectiveness of the treatment was assessed by
      determining the number of colony forming units (CFU) remaining following exposure
      of the bacteria to HIFU. Most of the biofilms treated at the higher exposures of
      6.2 and 7.6 MPa had no detectable CFU, indicating that bacteria in the biofilm
      were killed by the treatment or that treatment disrupted the biofilm and released
      bacteria from the slide. However, the ability of some bacteria to survive at the
      higher exposure settings needs to be resolved prior to implementing the treatment
      clinically.

PMID- 19171417
TI  - Development of carcinoid tumour in hormonally treated adenocarcinoma of the
      prostate.
AB  - We present the case of an 81-yr-old man with a prostatic adenocarcinoma and a
      metastatic carcinoid. Simultaneous occurrence of hormonally treated
      adenocarcinoma of the prostate and a carcinoid has been described before. The
      pathogenesis of this coincidence is largely unclear; however, androgen
      deprivation therapy might play a key role in neuroendocrine differentiation of
      adenocarcinoma cells. Early recognition of the carcinoid syndrome is crucial, as
      surgical cure is not possible after metastasis. We provide a brief review of
      recent literature.

PMID- 19171418
TI  - Preservation of lateral prostatic fascia is associated with urine continence
      after robotic-assisted prostatectomy.
AB  - BACKGROUND: Among several clinical factors, nerve or prostatic fascia
      preservation is associated with an improved continence outcome in several
      studies. OBJECTIVE: We study the clinical aspects associated with urine
      continence after prostatectomy, paying special attention to the extent and
      location of fascia preservation. DESIGN, SETTING, AND PARTICIPANTS: European
      Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30
      (QLQ-C30) and Prostate Cancer Module (PR25) questionnaires were used to evaluate
      quality-of-life (QoL) parameters prior to and at 6 and 12 mo after surgery for
      151 men treated with robot-assisted laparoscopic prostatectomy (RALP) for
      localised prostate cancer. Fascia preservation was scored at 12 locations around
      the circumference of the prostate. Any involuntary urine loss showed a strong
      correlation with several domains of the EORTC QLQ-C30 and was therefore chosen as
      the definition of urine incontinence. INTERVENTION: Robot-assisted laparoscopic
      prostatectomy (RALP). MEASUREMENTS: Any urine incontinence. RESULTS AND
      LIMITATIONS: Of the preoperative and intraoperative characteristics, a low fascia
      preservation (FP) score and a higher score for preoperative voiding complaints
      (EORTC QLQ-P25 domain 1) were associated with an increased risk of urine
      incontinence and pad use at 6 and 12 mo postoperatively. In the multivariate
      binary logistic regression analysis, the extent of fascia preservation at the
      lateral aspects of the prostate as assessed by the FP score was the best
      predictor of urine continence at 6 and 12 mo postoperatively. The odds ratio for
      urine incontinence in men with preservation of the lateral prostatic fascia was
      0.378 (95% CI, 0.121-0.624) and 0.289 (95% CI, 0.201-0.524) for preservation at
      the right and left aspects, respectively. This is a retrospective analysis not
      containing pad-test data. CONCLUSIONS: Fascia preservation at the lateral aspect
      of the prostate was the best predictor of urine continence after RALP. These data
      suggest that preservation of fascial support lateral rather than dorsolateral to
      the urethra and prostate may protect neurovascular structures important to
      improving postprostatectomy urine continence.

PMID- 19171419
TI  - Editorial comment on: Preservation of lateral prostatic fascia is associated with
      urine continence after robotic-assisted prostatectomy.

PMID- 19171420
TI  - Editorial comment on: Preservation of lateral prostatic fascia is associated with
      urine continence after robotic-assisted prostatectomy.

PMID- 19171421
TI  - Synergistic effect of Sorafenib and Sunitinib with Enzastaurin, a selective
      protein kinase C inhibitor in renal cell carcinoma cell lines.
AB  - Enzastaurin (LY317615.HCl) is an oral selective PKC-beta inhibitor with
      antiproliferative efficacy in various tumor models. This study was designed to
      investigate whether combination therapy with Enzastaurin and other targeted
      agents including Sorafenib and Sunitinib enhanced anti-tumor efficacy in renal
      cell carcinoma cell lines. Enzastaurin alone presented not active in renal cell
      carcinoma cell lines. Both Sorafenib and Sunitinib with Enzastaurin at
      concentrations feasible in vivo showed a synergistic reduction of viable RCC
      cells by inhibiting cell growth through inhibition of phospho-S6-kinase and GSK3
      beta. The combination of Enzastaurin with Sorafenib and Sunitinib seems highly
      encouraging and warrants further investigation in vivo.

PMID- 19171422
TI  - SAGE analysis highlights the importance of p53csv, ddx5, mapkapk2 and ranbp2 to
      multiple myeloma tumorigenesis.
AB  - Serial analysis of gene expression (SAGE) allows a comprehensive profiling of
      gene expression within a given tissue and also an assessment of transcript
      abundance. We generated SAGE libraries from normal and neoplastic plasma cells to
      identify genes differentially expressed in multiple myeloma (MM). Normal plasma
      cells were obtained from palatine tonsils and MM SAGE library was generated from
      bone marrow plasma cells of MM patients. We obtained 29,918 SAGE tags from normal
      and 10,340 tags from tumor libraries. Computer-generated genomic analysis
      identified 46 upregulated genes in the MM library. Ten upregulated genes were
      selected for further investigation. Differential expression was validated by
      quantitative real-time PCR in purified plasma cells of 31 patients and three
      controls. P53CSV, DDX5, MAPKAPK2 and RANBP2 were found to be upregulated in at
      least 50% of the MM cases tested. All of them were also found upregulated in MM
      when compared to normal plasma cells in a meta-analysis using ONCOMINE microarray
      database. Antibodies specific to DDX5, RANBP2 and MAPKAPK2 were used in a TMA
      containing 57 MM cases and confirmed the expression of these proteins in 74%,
      96%, and 21% of the MM samples, respectively. Analysis of differential expression
      using SAGE could identify genes important for myeloma tumorigenesis (P53CSV,
      DDX5, MAPKPK2 and RANBP2) and that could potentially be useful as therapeutic
      targets.

PMID- 19171423
TI  - Reduction of 2,4,6-trichlorophenol with zero-valent zinc and catalyzed zinc.
AB  - Reductive dechlorination of 2,4,6-trichlorophenol (2,4,6-TCP) was conducted with
      Zn and Zn bimetals, Pd/Zn, Ni/Zn, Cu/Zn, Pt/Zn. Zn showed relatively low reaction
      rate toward 2,4,6-TCP, while Pd/Zn had dramatically increased reactivity and
      other bimetals had higher reaction rates than that of plain zinc. Phenol and less
      chlorinated phenols were found as dechlorination products. Pd/Zn produced
      cyclohexanone which is a product of aromatic ring reduced. Surface area
      normalized kinetic constants and second metal contents normalized kinetic
      constants were calculated and compared. Two mechanisms, mainly catalytic
      activation and enhanced corrosion, were proposed for the reactivity enhancement.

PMID- 19171424
TI  - Thermodynamic analysis of the selective chlorination of electric arc furnace
      dust.
AB  - The remelting of automobile scrap in an electric arc furnace (EAF) results in the
      production of a dust, which contains high concentrations of the oxides of zinc,
      iron, calcium and other metals. Typically, the lead and zinc are of commercial
      value, while the other metals are not worth recovering. At the present time, EAF
      dusts are treated in high temperature Waelz rotary kiln-type processes, where the
      lead and zinc oxides are selectively reduced and simultaneously reoxidized and a
      crude zinc oxide is produced. Another alternative processing route is selective
      chlorination, in which the non-ferrous metals are preferentially chlorinated to
      their gaseous chlorides and in this manner separated from the iron. In the
      present research, a detailed thermodynamic analysis of this chlorination process
      has been performed and the following factors were investigated; temperature,
      amount of chlorine, lime content, silica content, presence of an inert gas and
      the oxygen potential. High lead and zinc recoveries as gaseous chlorides could be
      achieved but some of the iron oxide was also chlorinated. Additionally, the
      calcium oxide in the dust consumes chlorine, but this can be minimized by adding
      silica, which results in the formation of stable calcium silicates. The optimum
      conditions were determined for a typical dust composition. The selectivities
      achieved with chlorination were lower than those for reduction, as reported in
      the literature, but there are other advantages such as the potential recovery of
      copper.

PMID- 19171425
TI  - Deodorization of swine manure slurry using horseradish peroxidase and peroxides.
AB  - Considering the development of highly confined piggery and increasing complaints
      about livestock manure odors, it is pressing to develop a practical way to reduce
      the odors. Peroxidase, which has been proved to be capable of removing toxic
      phenolic compounds from wastewater, may also be effective in deodorizing the
      swine manures. Horseradish peroxidase (HRP) (0.1-3.0 U/mL) with hydrogen peroxide
      (H(2)O(2), 0.5-6%) or calcium peroxide (CaO(2), 0.1-3.0g) was examined for the
      efficiency of controlling the release of seven malodor compounds, including three
      volatile fatty acids (isobutyric acid, isocaproic acid and isovaleric acid), two
      phenolic compounds (phenol and p-cresol) and two indolic compounds (indole and
      skatole) from swine manure slurry. Odor intensity and total nitrogen content in
      swine manure were also measured. The results showed almost 100% reduction in p
      cresol, 54-84% reduction in odor intensity, 32-54% reduction in indolic compounds
      and 28-41% reduction of VFAs. The effect of deodorization can last for at least
      48 h.

PMID- 19171426
TI  - Co-remediation of the lead-polluted garden soil by exogenous natural zeolite and
      humic acids.
AB  - The current study reported the co-remediation effect on the lead-polluted garden
      soil by zeolite and humic acids (HA), which was from comparing with the
      remediation of single zeolite in term of the lead fraction of sequential
      extraction in the soil and the distribution of lead in different parts of rape.
      Mixed treatment (zeolite and HA) and single treatment (zeolite) were,
      respectively, applied to the artificially polluted garden soil to examine the
      difference of their remediation effects in pot experiment. Results indicated that
      the co-remediation led to significantly greater (p<0.01) reduction in the lead
      concentration in plants than by singly adding to zeolite. The co-application of
      zeolite and HA reduced the available fraction of lead compounds, but slightly
      increased (p<0.01) the water-soluble fraction of lead compounds in the garden
      soil, compared with the application of single zeolite, especially in the severe
      lead-polluted soil (> or =1000 mg kg(-1)). This method might be an efficient way
      to remediate the lead-polluted soils on a large scale, although zeolite is a kind
      of hazardous material.

PMID- 19171427
TI  - Fractionation study in bioleached metallurgy wastes using six-step sequential
      extraction.
AB  - The stored metallurgy wastes contain residues from ore processing operations that
      are characterized by relatively high concentrations of heavy metals. The
      bioleaching process makes use of bacteria to recover elements from industrial
      wastes and to decrease potential risk of environmental contamination. Wastes were
      treated by solutions containing bacteria. In this work, the optimized six-stage
      sequential extraction procedure was applied for the fractionation of Ni, Cr, Fe,
      Mn, Cu and Zn in iron-nickel metallurgy wastes deposited in Southern Poland
      (Szklary). Fractionation and total concentrations of elements in wastes before
      and after various bioleaching treatments were studied. Analyses of the extracts
      were performed by ICP-MS and FAAS. To achieve the most effective bioleaching of
      Zn, Cr, Ni, Cu, Mn, Fe the usage of both autotrophic and heterotrophic bacteria
      in sequence, combined with flushing of the residue after bioleaching is required.
      80-100% of total metal concentrations were mobilized after the proposed
      treatment. Wastes treated according to this procedure could be deposited without
      any risk of environmental contamination and additionally the metals could be
      recovered for industrial purposes.

PMID- 19171428
TI  - A comparative study of multicomponent adsorption of phenolic compounds on GAC and
      ACFs.
AB  - The impact of adsorbent pore size distribution (PSD) and adsorbate critical
      oxidation potential (COP) on competitive adsorption on activated carbon were
      investigated in this study. Three activated carbons with different pore size
      distribution were used as adsorbents--granular activated carbon (GAC) F400, and
      two activated carbon fibers (ACFs), namely ACC-10 and ACC-15. Binary adsorptions
      of 2-methylphenol/2-chlorophenol and 2-methylphenol/2-nitrophenol were conducted
      on all three adsorbents. Ternary adsorption of 2-methylphenol/2-nitrophenol/2
      chlorophenol was conducted on ACC-15 and F400. 2-Nitrophenol was more physically
      adsorbable than the other two adsorbates, while 2-methylphenol was the easiest to
      get oligomerized due to its low COP. ACC-10, which has the smallest critical pore
      size and narrow PSD, was shown to be effective in hampering oligomerization of
      phenolic compounds in all binary adsorption systems. ACC-15, which has larger
      critical pore size than ACC-10 and also narrow PSD, showed somewhat effectiveness
      in hampering oligomerization in binary adsorption systems and total effectiveness
      in ternary adsorptions. On the other hand, the wide pore size variations of F400
      played a role in the oligomerization of the phenolic compounds. The Ideal
      Adsorbed Solution Theory (IAST) well predicted the multicomponent adsorption
      systems that did not undergo oligomerization.

PMID- 19171429
TI  - Sorption isotherm and kinetic modeling of aniline on Cr-bentonite.
AB  - In this paper, the sorption characteristics of aniline on Cr-bentonite prepared
      using synthetic wastewater containing chromium was investigated in a batch system
      at 30 degrees C. The effects of relevant parameters, such as pH value of
      solution, adsorbent dosage and initial aniline concentration were examined. The
      experimental data were analyzed by the Langmuir and Freundlich, and Temkin models
      of sorption. The sorption isotherm data were fitted well to Langmuir isotherm and
      the monolayer sorption capacity was found to be 21.60 mg/g at 30 degrees C.
      Dubinin-Redushkevich (D-R) isotherm was applied to describe the nature of aniline
      uptake and it was found that it occurred chemically. The kinetic data obtained at
      different concentrations were analyzed using a pseudo first-order, pseudo second
      order kinetic equation and intraparticle diffusion model. The experimental data
      fitted very well the pseudo second-order kinetic model. Intraparticle diffusion
      affects aniline uptake. The results indicate that there is significant potential
      for Cr-bentonite as an adsorbent material for aniline removal from aqueous
      solutions.

PMID- 19171430
TI  - Trigeminal neuralgia and pain related to multiple sclerosis.
AB  - Although many patients with multiple sclerosis (MS) complain of trigeminal
      neuralgia (TN), its cause and mechanisms are still debatable. In a multicentre
      controlled study, we collected 130 patients with MS: 50 patients with TN, 30
      patients with trigeminal sensory disturbances other than TN (ongoing pain,
      dysaesthesia, or hypoesthesia), and 50 control patients. All patients underwent
      pain assessment, trigeminal reflex testing, and dedicated MRI scans. The MRI
      scans were imported and normalised into a voxel-based, 3D brainstem model that
      allows spatial statistical analysis. The onset ages of MS and trigeminal symptoms
      were significantly older in the TN group. The frequency histogram of onset age
      for the TN group showed that many patients fell in the age range of classic TN.
      Most patients in TN and non-TN groups had abnormal trigeminal reflexes. In the TN
      group, 3D brainstem analysis showed an area of strong probability of lesion
      (P<0.0001) centred on the intrapontine trigeminal primary afferents. In the non
      TN group, brainstem lesions were more scattered, with the highest probability for
      lesions (P<0.001) in a region involving the subnucleus oralis of the spinal
      trigeminal complex. We conclude that the most likely cause of MS-related TN is a
      pontine plaque damaging the primary afferents. Nevertheless, in some patients a
      neurovascular contact may act as a concurring mechanism. The other sensory
      disturbances, including ongoing pain and dysaesthesia, may arise from damage to
      the second-order neurons in the spinal trigeminal complex.

PMID- 19171431
TI  - Reactive diffusion under Laplace tension.
AB  - Nanostructures such as nanospheres or nanowires may contain surfaces and
      interfaces of pronounced curvature. To investigate the impact of severe curvature
      on the kinetic of reactions, thin-film Al/Cu/Al and Cu/Al/Cu triple layers are
      deposited on tungsten tips of 25nm curvature radius. The thermal reaction of the
      layer structure is studied by atom probe tomography. Experiments demonstrate that
      the reaction rate depends significantly on the deposition sequence of metals.
      Interpretation of the observed reaction kinetics leads to the conclusion that
      under the influence of interfacial tension probably the two limiting cases of
      atomic transport, Darken and Nernst-Planck kinetics, are realized in dependence
      on the stacking sequence.

PMID- 19171432
TI  - A new approach for explanation of specimen rupture under high electric field.
AB  - Failure of needle-shaped specimens under the action of high electric fields is
      one of the most serious problems in many field-ionization devices and methods. It
      was shown that the length of what was removed during discharge part of specimens
      in most of the cases was several orders greater than that of an initial radius of
      the specimen apex. Experimental results obtained in this work indicate that
      electrical breakdown in field-ion microscopes is initiated by the impact of
      nanoparticles detached from a point anode in a high electric field. A new
      approach for explanation of an observed specimen failure in a high electric field
      was proposed, where the formation and expansion of the cathode plasma play the
      key role in the mechanical rupture and melting of field-ion tips. The expanding
      plasma behaves as a dynamic capacitor plate characterized by a high velocity and
      increasing field strength at the specimen tip. The field rise rate at a constant
      voltage in a dynamic plasma-to-tip capacitor is of the order of >10(20)V/m/s. The
      present experimental data along with the ecton model of the vacuum breakdown
      allow the results to be discussed as a mechanical sample failure under the action
      of the superhigh positive field pulse induced by the cathode plasma expansion.

PMID- 19171433
TI  - Fabrication and field emission properties of boron nanowire bundles.
AB  - We have successfully synthesized large-scale crystalline boron nanowire bundles
      (BNBs) by chemical vapor deposition method. Fe(3)O(4) nanoparticles were used as
      catalysts spreading on ceramic substrate during the reaction process. The bundles
      consisted of many thin boron nanowires with a mean diameter of about 25nm and a
      length of several micrometers. In addition, boron nanowires are single crystals
      with an alpha-tetragonal structure and grow along [001] orientation. These
      nanowires have a surface electron affinity of 3.76eV and a work function of
      4.54eV. A turn-on field of 5.1V/mum and a threshold field of 10.5V/mum were found
      in the nanowire bundles, and stable field emission was recorded at the same time.

PMID- 19171434
TI  - MicroRNA expression and its implications for the diagnosis and therapeutic
      strategies of breast cancer.
AB  - Alterations in microRNA (miRNA) expression have been associated with tumor
      suppression or tumorigenesis, metastasis and poor prognosis in human breast
      cancer. Deregulation of miRNAs is emerging as a major aspect of cancer etiology
      because their capacity to direct the translation and stability of targeted
      transcripts can dramatically influence cellular physiology. Some miRNAs were
      considered to be associated with molecular subtypes of breast cancer and
      correlated with specific breast cancer clinicopathological factors, such as HER2,
      estrogen and progesterone receptor level, tumor stage, vascular invasion, or
      proliferation index. The expression level of miRNAs as suppressors, which can
      inhibit the expression of tumor promoting genes, is frequently down-regulated in
      breast cancer. Multiple lines of evidence also demonstrated the involvement of
      specific miRNAs as oncogenes in breast tumorigenesis. Some miRNAs have been
      considered to have potential clinical applications as a novel biomarker for
      breast cancer diagnosis and prognostic factor. Exploitation of the therapeutic
      potential of RNA interference will be an important task and achieved through the
      further understanding of the mechanisms of gene regulation by miRNAs.

PMID- 19171435
TI  - Diurnal cortisol profiles and evening cortisol in post-pubertal adolescents
      scoring high on the Children's Depression Inventory.
AB  - Early-onset mood disorders have become a significant public health problem in
      recent years. The Children's Depression Inventory (CDI) is a commonly used self
      report measure. We studied the relation of CDI cut-offs to biological markers of
      depression such as the diurnal cortisol rhythm and evening cortisol. In 58 post
      pubertal adolescents (29 boys and 29 girls, M(age)=15.1 years), the diurnal
      cortisol profile was derived from three saliva samples, collected at awakening,
      at noon and in the evening on a week-end day. Longitudinal repeated measurements
      regression revealed that the group with CDI>18 (high depressive symptoms) clearly
      had a higher and flatter diurnal rhythm with elevated evening cortisol compared
      to either the group with CDI between 13 and 18 (moderate depressive symptoms) or
      CDI<13 (low depressive symptoms). Multinomial logistic regression indicated that
      evening cortisol was useful in classifying the adolescents in the high depressive
      symptoms group, while awakening and noon cortisol were not. Our results indicate
      that the type of high flattened profiles sometimes seen in individuals who are
      clinically depressed according to diagnostic interviews can also be identified
      with a self-report inventory, at high levels of symptom reporting. Given the
      complexity of conducting diagnostic interviews, this result bears clinical
      relevance.

PMID- 19171436
TI  - Ribonucleotide reductase inhibitors with erythropoietin and iron sulfate against
      malaria.

PMID- 19171437
TI  - Cortical stimulation with weak electrical currents for cognitive modulation in
      attention deficit hyperactivity disorder.

PMID- 19171438
TI  - Sclerosing angiomatoid nodular transformation of the spleen: case report.
AB  - Sclerosing angiomatoid transformation of the spleen (SANT) is a relatively new,
      rare, and unique lesion that involves the spleen. Less than 30 cases have been
      described to date. The lesion commonly affects middle-aged adults and shows a
      female predilection. It is often discovered incidentally through imaging. SANT is
      morphologically and immunohistochemically distinct. However, as it is a
      relatively new entity, misdiagnosis of SANT may lead to overtreatment of the
      patients. The pathogenesis of SANT is unknown. The lesion is entirely benign, and
      splenectomy is curative. We report a new case of SANT, with emphasis on the
      differential diagnosis and pathogenesis of SANT.

PMID- 19171439
TI  - Nested variant of urothelial carcinoma of the renal pelvis.
AB  - The nested variant of urothelial carcinoma is an uncommon form of urothelial
      carcinoma with distinctive histopathologic features. The majority of cases of
      this unusual type of urothelial carcinoma have been described in the urinary
      bladder, with examples of this neoplasm involving the upper urinary tract being
      extremely limited. The present report details the clinical and pathologic
      features of an unusual case of a nested variant of urothelial carcinoma occurring
      in the renal pelvis of a 71-year-old woman. The tumor was characterized by a
      nested pattern of growth and relatively bland cytologic features, and presented
      with locally advanced disease at the time of nephroureterectomy. Although rare,
      awareness that the nested variant of urothelial carcinoma may occur at this
      particular site is important so as not to confuse this unusual form of urothelial
      carcinoma with other pathologic lesions of the renal pelvis.

PMID- 19171440
TI  - A broadly adaptive array of dose-constraint templates for planning of intensity
      modulated radiation therapy for advanced T-stage nasopharyngeal carcinoma.
AB  - PURPOSE: To develop and validate adaptive dose-constraint templates in intensity
      modulated radiotherapy (IMRT) planning for advanced T-stage nasopharyngeal
      carcinoma (NPC). METHOD AND MATERIALS: Dose-volume histograms of clinically
      approved plans for 20 patients with advanced T-stage NPC were analyzed, and the
      pattern of distribution in relation to the degree of overlap between targets and
      organs at risk (OARs) was explored. An adaptive dose constraint template (ADCT)
      was developed based on the degree of overlap. Another set of 10 patients with
      advanced T-stage NPC was selected for validation. Results of the manual arm
      optimization protocol and the ADCT optimization protocol were compared with
      respect to dose optimization time, conformity indices, multiple-dose end points,
      tumor control probability, and normal tissue complication probability. RESULTS:
      For the ADCT protocol, average time required to achieve an acceptable plan was 9
      minutes, with one optimization compared with 94 minutes with more than two
      optimizations of the manual arm protocol. Target coverage was similar between the
      manual arm and ADCT plans. A more desirable dose distribution in the region of
      overlap between planning target volume and OARs was achieved in the ADCT plan.
      Dose end points of OARs were similar between the manual arm and ADCT plans.
      CONCLUSIONS: With the developed ADCT, IMRT treatment planning becomes more
      efficient and less dependent on the planner's experience on dose optimization.
      The developed ADCT is applicable to a wide range of advanced T-stage NPC
      treatment and has the potential to be applied in a broader context to IMRT
      planning for other cancer sites.

PMID- 19171441
TI  - [Bariatric surgery and obstetrics].
AB  - Obesity poses a significant risk to reproductive-aged women. Weight reduction
      before conception is the best way to increasing fertility and reduces obesity
      associated morbidity. When medical interventions fail, bariatric surgery is the
      most successful method of weight loss, effective increasing fertility and
      reducing obstetrical complications and maternal and neonatal morbidity comparing
      obese women. Gastric banding and gastric bypass are the most increasingly
      utilized treatment option in France and should be offered to morbidly obese women
      of childbearing age. This literature review provides information about different
      techniques of bariatric surgery and about the multidisciplinary management of
      these pregnancies (monitoring, micronutrient supplementation) to promote maternal
      and fetal wellbeing in concert with continuing postoperative weight control.

PMID- 19171442
TI  - Characterization of an outbreak of astroviral diarrhea in a group of cheetahs
      (Acinonyx jubatus).
AB  - A Mamastrovirus was identified in an outbreak of diarrhea in cheetahs (Acinonyx
      jubatus). Five young adult and two adult cheetahs presented with lethargy,
      anorexia, watery diarrhea and regurgitation over an 11-day period. Fecal samples
      were submitted for electron microscopy and culture. Electron microscopy results
      revealed particles morphologically consistent with an astrovirus, and no other
      viral pathogens or significant bacterial pathogens were identified. The
      astrovirus was confirmed and sequenced using consensus astroviral PCR, resulting
      in a 367 base pair partial RNA-dependent-RNA polymerase (RdRp) product and a 628
      base pair partial capsid product. Bayesian and maximum likelihood phylogenetic
      analyses were performed on both the RdRp and the capsid protein segments. All
      animals were monitored and treated with bismuth subsalicylate tablets (524mg PO
      BID for 5 days), and recovered without additional intervention. This is the first
      report we are aware of documenting an astrovirus outbreak in cheetah.

PMID- 19171443
TI  - Development of a multiplex qPCR for detection and quantitation of pathogenic
      intestinal spirochaetes in the faeces of pigs and chickens.
AB  - Anaerobic intestinal spirochaetes of the genus Brachyspira include several
      important pathogenic species, particularly those infecting pigs and chickens. In
      this study a multiplex-quantitative polymerase chain reaction (M-qPCR) assay was
      developed based on amplification of a 198 base pair portion of the NADH oxidase
      gene, using TaqMan probes for detecting and quantifying the three main pathogenic
      species, B. hyodysenteriae, B. pilosicoli and B. intermedia. The specificity of
      the assay was validated using 130 spirochaete strains belonging to members of the
      seven officially named and two provisionally named Brachyspira species. The
      detection limit for all three targeted species was 1-10 viable cells and 10 fg
      DNA per reaction. Further detection limit testing was conducted on porcine and
      chicken faecal specimens that were spiked with spirochaete cells before DNA
      extraction. The assay could detect 10(2) to 10(3)cells per 0.2g of sample, giving
      an improved detection threshold compared to standard PCRs. The M-qPCR was further
      developed by incorporating a novel internal control (IC) that employed host cells
      as template DNA. This adaptation allowed monitoring of the quality of the
      extracted DNA and ensured that there was no inhibition of the PCR reaction. Use
      of the IC further improved the detection limits of the assay and increased
      confidence in being able to detect low numbers of pathogens in faecal samples.
      Taken together, the results indicate that the new M-qPCR assay is a valuable tool
      for detecting and quantifying low numbers of pathogenic intestinal spirochaetes
      in the faeces of pigs and chickens, and potentially other species.

PMID- 19171444
TI  - Reproductive performance of donor mares subsequent to eFSH treatment in early
      vernal transition: Comparison between the first, second, and mid-season estrous
      cycles of the breeding season.
AB  - The objective was to compare the reproductive performances associated with the
      first (Cycle-1), second (Cycle-2), and mid-season (MS-Cycle) ovulations of the
      breeding season in donor mares that were treated with equine-FSH (eFSH) in the
      early vernal transition. Mares (n=15) kept under ambient light were examined
      ultrasonographically per-rectum starting January 30. When an ovarian follicle >
      or =25mm in diameter was detected, twice daily eFSH treatments were initiated.
      The eFSH treatments ceased when a follicle > or =35mm was detected, and 36h later
      hCG was administered. Thereafter, mares were artificially inseminated every 48h
      until ovulation (Day 0). Trans-cervical embryo recovery attempts were performed
      on Day 8, and subsequently PGF2alpha was administered. Equine FSH was not
      administered in the subsequent estrous cycles. In Cycle-2 and in the MS-Cycle,
      hCG was administered when a follicle > or =35mm was detected; breeding, embryo
      recovery, and PGF2alpha administration, were similar to Cycle-1. Mares had an
      untreated estrous cycle (no treatment or breeding) between Cycle-2 and the MS
      Cycle. All mares developed follicle(s) > or =35mm after 4.9+/-0.6 days of eFSH
      treatment, and subsequently ovulations occurred; mean (95% CI) interval from
      treatment initiation to ovulation was 7.9 (6.5-9.3) days. The number of
      preovulatory follicles (> or =30mm) at the time of hCG administration (Cycle-1:
      2.2+/-0.3 compared with Cycle-2: 1.0+/-0 compared with MS-Cycle: 1.1+/-0.1
      follicles), and the number of ovulations (2.5+/-0.4 compared with 1.0+/-0
      compared with 1.1+/-0.1 ovulations) were greater (p<0.05) in Cycle-1.
      Nevertheless, mean embryo numbers did not differ among cycles (0.8+/-0.2 compared
      with 0.5+/-0.1 compared with 0.5+/-0.1 embryo/mare). On average, embryo
      morphology grade was less (p<0.05) in Cycle-1 as compared to non-eFSH cycles
      (combined Cycle-2 and MS-Cycle). This impaired embryo quality could be due to a
      seasonal effect, or negative effect of the eFSH treatment, which was possibly
      related to alterations in the hormonal environment (estradiol-17beta and
      progesterone). A prolonged IOI (>21 days) was recorded in 7 of 15 mares following
      the Cycle-1 ovulation, but not subsequently. In conclusion, eFSH treatment of
      vernal transitional donor mares stimulated ovulation within only few days of
      treatment, and the following embryo recovery rate was at least as good as in the
      subsequent estrous cycles; however, on average, embryos were morphologically
      impaired. In subsequent estrous cycles in the breeding season, ovulations, embryo
      recovery rates, and embryo variables did not appear to be negatively affected;
      however, the first inter-ovulatory interval of the breeding season was prolonged
      in approximately half of the mares.

PMID- 19171445
TI  - The dialectic role of progesterone.
AB  - Progesterone is known to be metabolized into various metabolites exerting various
      effects, predominantly into 5alpha-pregnanes and 4-pregnenes. Studies on uterine
      tissues showed numerous progesterone-converting enzymes such as 5alpha-reductase
      (5alphaR), 5beta-reductase, 3alpha-, 3beta-, 20alpha-, and 20beta-hydroxysteroid
      oxidoreductases and others. The main progesterone-metabolizing enzymes in human
      breast tissues are 5alphaR, 3alpha-HSO 3beta-HSO, and 20alpha-HSO. Tumor genesis
      in the breast has been shown to be enhanced by high 5alphaR activity and
      suppression of 3alpha-HSO and 20alpha-HSO. A major determinant of 5alphaR, the
      breast's gate-keeping enzyme activity is the genetic variation in the enzyme's
      gene. Two polymorphisms within the steroid 5alphaR type 2 gene, Ala>Thr at codon
      49 and Val>Leu at codon 89 have been reported to strongly affect the enzyme's
      activity, even in regard to breast cancer risk. As steroid hormones are known to
      be converted into many other steroids occupying different receptors and thereby
      exerting various different effects, progesterone receptors are important factors
      when mediating the hormone's effects. The progesterone receptor (PR) gene is
      transcribed from one gene by two alternative promoters and translated into PR-B,
      a potent transcriptional activator, and PR-A, the shorter isoform, necessary to
      oppose the effects of PR-B. In addition, endocrine reactions are modulated by
      epigenetics. The expression of progesterone receptors has been shown to be up-
      and downregulated by various epigenetic mechanisms. Many factors must be also
      taken into account in hormonal (replacement) therapy. Thus natural steroids
      should not be disparaged as treatment options for gender-specific diseases. An
      update on endocrinological knowledge and experience is rather mandatory for
      gynaecologists.

PMID- 19171446
TI  - Pathophysiologic evaluation of MELAS strokes by serially quantified MRS and CASL
      perfusion images.
AB  - PURPOSE: To clarify the roles of serial MR spectroscopy (MRS) and continuous
      arterial spin labeling (CASL) perfusion images for evaluating cerebral lesions in
      patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke
      like episodes (MELAS). MATERIALS AND METHODS: Two cases of MELAS followed up
      serially using MRS and CASL images in addition to routine MR imaging were
      enrolled. RESULTS: Newly appeared lesions assessed by MRS revealed increased
      lactate doublets which correlated well with CSF lactate level, and these showed a
      decreasing trend after treatment, although conventional T2 weighted images
      revealed hyper-intensity in both phases. Spectra from normally appearing white
      matter depicted slight lactate peaks during clinical exacerbation periods with
      marked elevation of CSF lactate and showed a decreasing NAA concentration during
      the prolonged course. In CASL images, acute lesions of the disease were clearly
      visible as hyper-perfusion foci, and chronic lesions were demonstrated as hypo-
      or iso-perfusion regions. CONCLUSION: The detection of lactate peaks in the MR
      spectrum from normally appearing white matter may be considered as systemic
      lactic acidosis or an exacerbation of MELAS, and active lesions can be
      distinguished from chronic inactive lesions by the increase of lactate peaks in
      MRS or the state of hyper-perfusion in CASL images.

PMID- 19171447
TI  - Development and validation of a stability-indicating RP-HPLC method to separate
      low levels of dexamethasone and other related compounds from betamethasone.
AB  - Betamethasone (BM) is an active pharmaceutical ingredient (API) or an
      intermediate which is used to manufacture various finished pharmaceutical
      products. Betamethasone is also used as a starting material to manufacture other
      APIs that are related to this steroid family. It is quite a challenging task to
      separate dexamethasone (DM) peak (the alpha epimer) and other structurally
      related compounds from BM. A stability-indicating reversed-phase high performance
      liquid chromatography (RP-HPLC) method has been developed which can separate and
      accurately quantitate low levels of DM and other related compounds from BM and
      also from each other. This method was successfully validated for the purpose of
      conducting stability studies of betamethsone in quality control (QC)
      laboratories. The stability-indicating capability of this method was demonstrated
      by adequate separation of DM and all the degradation product peaks from BM peak
      and also from each other in aged stability samples of betamethasone. A gradient
      mobile phase system consisting of (A) water:acetonitrile (90:10, v/v) and (B)
      acetonitrile:isopropanol (80:20, v/v) was used with an ACE Phenyl column (10 cm x
      4.6 mm, 3 microm particles, 100 A pore size) and an ultraviolet (UV) detection at
      240 nm.

PMID- 19171449
TI  - Micrometastases and isolated tumour cells in sentinel lymph nodes in oral and
      oropharyngeal squamous cell carcinoma.
AB  - BACKGROUND: The occurrence of micrometastases (MMs) and isolated tumour cells
      (ITCs) in oral sentinel lymph node (SLN) biopsy is poorly known, and the
      definitions and clinical significance of MMs and ITCs in SLN biopsy are
      controversial. We compared the UICC/TNM definitions of MMs and ITCs with our
      previously published sentinel node protocol to assess how the adoption of the
      UICC/TNM criteria would affect the staging of nodal micrometastatic disease.
      METHODS: Of 107 patients who had a SLN biopsy and pathology at 150 microm
      intervals, 35 with metastatic tumour were included. Eighty-six SLNs were
      reassessed using the UICC/TNM definitions for MMs and ITCs. Findings were linked
      to the final pathology in the subsequent neck dissection. RESULTS: Initial H&E
      sections showed metastases in 24 patients (in 34 out of 61 SLN), 8 of whom (9
      SLNs) had MMs. Additional step serial sections revealed metastatic deposits in a
      further 11 patients (15 out of 25 SLNs were positive) which were reassessed as
      MMs (6 patients) or ITCs (5 patients). Subsequent neck dissection revealed
      additional metastases in 46% of patients with MM, whilst one of the ITC patients
      had subsequent neck metastases (20%). CONCLUSION: Despite some limitations, the
      UICC/TNM classification provides an objective, uniform method of detecting MMs
      and ITC's. Unlike in cases with ITC, metastases in other non-SLNs were common
      when a micrometastasis was detected in a SLN, indicating need for further
      treatment of the neck.

PMID- 19171448
TI  - Language, literacy, and characterization of stroke among patients taking warfarin
      for stroke prevention: Implications for health communication.
AB  - OBJECTIVE: Warfarin is a medication commonly prescribed to prevent strokes
      associated with certain medical conditions such as atrial fibrillation; however,
      little is known about how people taking warfarin perceive the goal of therapy and
      how they describe strokes. We assessed the stroke-related health literacy of
      anticoagulated patients to inform ways in which to improve health communication
      among people taking warfarin. METHODS: We conducted a mixed-methods study of an
      ethnically and linguistically diverse sample of people taking warfarin to prevent
      stroke (N=183) and measured literacy using the short-form Test of Functional
      Health Literacy in Adults. We asked participants to (1) describe their indication
      for warfarin, and (2) describe a stroke. Transcribed answers were coded as
      concordant or discordant with established indications for warfarin and
      definitions of stroke. RESULTS: Forty-three percent of participants provided a
      discordant response when describing their indication for warfarin. Only 9.3%
      reported that the purpose of taking warfarin was to prevent stroke. Not speaking
      English [OR=2.4 (1.1-5.6)] and less than a college education [OR=3.3 (1.4-7.3)]
      were independently associated with discordant answers about warfarin. Nearly 40%
      of subjects had inaccurate perceptions of stroke, and only one-third of subjects
      described a symptom or sign of stroke. Among English and Spanish-speaking
      participants, inadequate literacy was strongly associated with discordant
      responses about stroke [OR=5.8 (2.1-15.6)]. CONCLUSION: Among high-risk people
      taking warfarin to prevent stroke, significant gaps in stroke-related health
      literacy exist. These gaps likely represent mismatches in the ways clinicians
      teach and patients learn. PRACTICE IMPLICATIONS: Since stroke risk awareness and
      early recognition of the signs and symptoms of stroke are critical aspects of
      stroke prevention and treatment, clinicians should more strongly link warfarin
      therapy to stroke prevention and ensure that patients know the presenting
      symptoms and signs of stroke. Public health communication strategies regarding
      stroke prevention need to target individuals with limited literacy and limited
      English proficiency.

PMID- 19171450
TI  - Metachronous hepatic metastases from gastric carcinoma: a multicentric survey.
AB  - BACKGROUND: The treatment of hepatic metastases from gastric cancer is
      controversial, due to biologic aggressiveness of the disease. OBJECTIVE: To
      survey the clinical approach to the subset of patients presenting with
      metachronous hepatic metastases as sole site of recurrence after curative
      resection of gastric cancer, focusing on the results achieved by different
      therapies and to investigate the prognostic factors of major clinical relevance.
      METHODS: Retrospective multi-center chart review evaluating 73 patients,
      previously submitted to D >or= 2 gastrectomy for gastric cancer, who developed
      exclusive hepatic recurrence. Prognostic factors related to the patient, to the
      gastric malignancy and its treatment, and to the metastatic disease and its
      therapy were evaluated. RESULTS: Forty-five patients received supportive care, 17
      were submitted to chemotherapy, and 11 to hepatic resection. Survival was
      independently influenced by the variables T (p=0.019), N (p=0.05) and G (p=0.018)
      of the gastric primary and by the therapeutic approach to the metastases
      (p<0.005). In particular, T4 gastric cancer, presence of lymph-node metastases
      and G3 tumor displayed a negative prognostic value. Therapeutic approach to the
      metastases was the principal prognostic variable: 1, 2, and 3 years survival
      rates were 22.2%, 4.4% and 2.2%, respectively, for patients without specific
      treatment; 44.9%, 12.8% and 6.4% after chemotherapy (p=0.08) and 80.8%, 30.3% and
      20.2% after surgical resection (p<0.001). CONCLUSIONS: Our data suggest some
      clinical criteria that may facilitate selection of therapy for patients with
      hepatic recurrence after primary gastric cancer resection. The best survival
      rates are associated with surgical treatment, which should be chosen whenever
      possible.

PMID- 19171451
TI  - [Is the switch of fluoroquinolones from intravenous to oral administration useful
      in an intensive care unit? Economical approach].

PMID- 19171452
TI  - In vitro and in vivo effect of IFNalpha on B16F10 melanoma in two models:
      subcutaneous (C57BL6J mice) and lung metastasis (Swiss mice).
AB  - Interferon alpha tends to be the only agent used to treat melanoma. The objective
      of this study was to assess the effect of interferon alpha on the growth of the
      B16F10 melanoma, both in vitro and in vivo. We study the in vitro effect of
      interferon alpha (250,000, 500,000 and 1,000,000 IU/ml) on the B16F10 melanoma
      cell line (at 24, 48 and 72 h) and the in vivo effect in a subcutaneous (1x10(6)
      cells; 300,000 IU) and a pulmonary metastatic model (5x10(5) cells/lateral vein
      of the tail; 300,000, 600,000 and 1,200,000 IU). Necropsy included a
      morphological and immunohistochemical study (subcutaneous model), while the
      number of superficial lung metastases, implantation percentage and growth and
      invasion indices were calculated in the latter model. In vitro, interferon alpha
      decreased cell survival in a time- and dose-dependent manner; 250,000 IU/ml: 77%
      (24h), 80% (48 h) and 92% (72 h); 500,000 IU/ml: 62% (24h), 32% (48 h), 20% (72
      h); 1,000,000 IU/ml: 41% (24h), 16% (48 h), 10% (72 h). In the subcutaneous
      model, it reduced tumor weights (77.74%) and cell proliferation (70.8%), and
      increased necrotic areas (8%) and inflammatory infiltrates (34.46%). Metastatic
      model: 300,000 IU reduced pleural nodules by 38.79%, implantation by 59.42%,
      growth by 43.48%, invasion by 25.06%; the corresponding figures for 600,000 and
      1,200,000 IU were 38.79, 59.42, 43.48, 25.06%, and 65.55, 84.98, 56.52, 66.19%,
      respectively. Interferon alpha inhibited cell proliferation in all the models and
      had immunomodulatory (subcutaneous model) and antimetastatic (pulmonary
      metastatic model) effects in vivo.

PMID- 19171453
TI  - [Pharmacological treatment of stable chronic obstructive pulmonary disease].
AB  - The pharmacological treatment of chronic obstructive pulmonary disease (COPD) can
      significantly improve quality of life by reducing exacerbations, dyspnea and
      exercise intolerance, thereby limiting the degree of handicap and improving daily
      activities. Recently, large randomised trials showed that some treatments can
      alter the decline in FEV1, which was previously only accessible to smoking
      cessation, and maybe reduce mortality. Bronchodilators are the first-line
      pharmacological treatment of COPD. Their clinical efficacy cannot be predicted by
      the inconstant changes in FEV(1.) Their main mechanism of action is the reduction
      in lung hyperinflation. Theophylline has a lower efficacy/tolerance ratio than
      inhaled bronchodilators. In symptomatic patients with FEV1 <50/60% predicted and
      repeated exacerbations despite bronchodilators, inhaled corticosteroids combined
      with long acting beta-agonists can be used. Several other approaches targeting
      inflammation and oxidative stress, remodelling and lung regeneration are also
      being studied. Medications must be associated with non-pharmacological measures
      (including help towards smoking cessation, education, exercise training...).
      Systemic manifestations of COPD must also be taken into account.

PMID- 19171454
TI  - [Pulmonary function tests in chronic obstructive pulmonary disease].
AB  - The diagnosis of chronic obstructive pulmonary disease (COPD) relies on the
      presence of chronic airflow limitation poorly reversible or not reversible at
      all, defined by an FEV1/FVC ratio less than 70%. Stages of severity of COPD are
      defined according to the level of post-bronchodilator FEV1: > 80% of the
      predicted value (stage I); 50-80% (stage II); 30-50% (stage III); < 30% (stage
      IV). Accordingly, the measurement of pulmonary volumes (spirometry) is required
      for the diagnosis but also for the follow-up of COPD patients. The investigations
      which are required depend on the severity of COPD: spirometry and flow-volume
      curves during forced expiration are sufficient in stage I; measurement of static
      lung volumes and bronchodilator reversibility testing are required in stage II.
      Arterial blood gases should be measured in stages III and IV. Pulse oxymetry and
      6minute walk test (6MWT) are recommended from stage II. For appreciating the
      severity of COPD and for the follow-up of patients it is recommended to evaluate
      other variables than FEV1: results of the 6MWT, level of dyspnea, body mass
      index. The results of FEV1 and of these variables are included in the recently
      developed BODE index. Measurement of CO transfer capacity is recommended in the
      presence of emphysema; cardiopulmonary exercise testing (bicycle) is recommended
      before initiating exercise training.

PMID- 19171455
TI  - [Prurigo].
AB  - Prurigo is a medical term which includes several clinical, pathological and
      etiologic entities. Diagnostic and therapeutic management is different depending
      on if we face acute prurigo or chronic prurigo. Acute prurigo is almost always
      linked to parasites or insects. Chronic prurigo can be linked to dermatologic
      diseases or may reveal internal pathologies. Complementary exams we should ask
      for are focused on these diseases. Idiopathic chronic prurigo, without underlying
      disease, is the most frequent one. It needs regular survey, as it can reveal
      cutaneous or internal diseases after months or even years. Treatment of prurigo
      is treatment of the underlying disease. Symptomatic treatment against pruritus,
      topic or systemic, must be added.

PMID- 19171456
TI  - [Excess mortality and sudden unexpected death in epilepsy].
AB  - Patients with epilepsy have a two to three fold increased risk of death as
      compared to the age-matched general population. This increased risk of death
      primarily affects young adults with drug resistant epilepsy. Sudden unexpected
      death in epilepsy (SUDEP) is one of the main cause of mortality in that
      population, and appears to be the direct consequence of a seizure. The
      pathophysiology of SUDEP remains unclear, but a post-ictal central or obstructive
      apnea seems to represent the most likely mechanism. The risk of SUDEP is
      increased in patients with nocturnal seizures, generalized tonic-clonic seizures,
      and poor compliance. This risk can be decreased by nocturnal supervision. There
      is yet no consensus regarding the information about SUDEP that should be
      delivered to patients with epilepsy, but it seems reasonable to individualize
      this information according to each patient form of epilepsy.

PMID- 19171457
TI  - [Recovery of transportable organs after cardiac arrest].
AB  - The transplant of an allograft after cardiac arrest has been allowed in France
      since 2005 (decree of 2 august 2005: art R.1232-4-1, 2 and 3 of the public health
      code). Recently, according to the international scale, 4 situations that could
      lead to the realization of transplantable organs after cardiac arrest were
      identified according to a classification called "Maastricht" which describes the
      potential donors. In France the donors of class III (cessation of all medical
      care) were excluded. Ethical questions concerning this new practice come up. Are
      criteria adopted to define death enough sure? What is the place of non-heart
      beating donor transplantation with new technical resuscitation as extracorporeal
      life support for prolonged cardiac arrest? How does family and medical staff live
      this protocol? Despite this, non heart-beating donor kidney transplants offer the
      opportunity to compensate for the growing discrepancy between supply and demand
      for donor kidneys. Results from foreign studies have shown that they have the
      same survival and long term function as kidneys from traditional brain-stem dead
      donors. This practice is defined by legislation and supervised by the "Agence de
      la biomedecine" which guarantees technical efficiency and respect of ethics.

PMID- 19171458
TI  - Morphine-methadone opioid rotation in cancer patients: analysis of dose ratio
      predicting factors.
AB  - The dose ratio that is effective when switching opioid therapy from morphine to
      methadone in cancer patients varies widely. There are no conclusive data
      explaining the source of this variability. We analyzed 54 cancer patients
      undergoing opioid rotation to clarify those factors that influenced the
      morphine/methadone dose ratio (MMEDR) at Day 10 after the switch. Reasons for
      switching were uncontrolled pain (10 patients) or side effects (with or without
      pain, 44 patients). Initial MMEDR was 5:1 or 10:1 (82% or 18% of patients,
      respectively). Multivariate regression analysis was used to identify the
      demographic, cancer-related, and treatment-related variables that were potential
      predictors of MMEDR. Median previous morphine dose for the entire sample was 220
      mg/day (range: 30-1000 mg/day). The stable MMEDR median was 5:1 (range: 2:1
      15:1). In the univariate analysis, reasons for opioid rotation, age, and previous
      morphine doses were associated with MMEDR. Multiple linear regression analysis
      showed that only the reason for switching (pain vs. side effects; P<0.001) and
      previous morphine doses (lower vs. upper to 300 mg/day; P<0.001) were associated
      with MMEDR. From this analysis, the MMEDRs for patients rotated for side effects
      at 300 mg/day or more or less than 300 mg/day of morphine were 9.1:1 or 5.6:1,
      respectively, and the MMEDRs for those switched for pain at 300 mg/day or more or
      less than 300 mg/day of morphine were 4.9:1 or 3:1, respectively. Both the
      reasons for opioid rotation and previous morphine doses are predictive factors
      and should be used to select the MMEDR more accurately.

PMID- 19171459
TI  - Using the Palliative Performance Scale to provide meaningful survival estimates.
AB  - Although there is a growing body of knowledge on survival prediction in
      populations with advanced cancer receiving palliative care using the Palliative
      Performance Scale (PPS), this literature has focused on disease, gender, and care
      location, and less is known about how to apply such knowledge to be clinically
      meaningful. To address this issue, we evaluated a database comprising 13 years of
      initial PPS scores on 6066 patients, which were recorded on their first
      assessment by the Victoria Hospice palliative care team in the home or palliative
      care unit setting. Our results reaffirmed PPS as a significant predictor of
      survival, with increasing survival times associated with higher PPS levels. We
      explored survival time distributions, a life expectancy table, and a survival
      nomogram as three potential ways to assist in estimating survival times in
      palliative care. We also evaluated the concept of Kaplan-Meier survival curve
      "nose-tail" refinement, and observed that this approach requires more research.
      More work is needed to better identify those who live "longer than expected" or
      die "sooner than expected" to provide clinical utility in discussion with
      patients and families.

PMID- 19171460
TI  - Topical analgesic combinations for bortezomib neuropathy.

PMID- 19171461
TI  - Impact of acute moderate elevation in left ventricular afterload on diastolic
      transmitral flow efficiency: analysis by vortex formation time.
AB  - BACKGROUND: The formation of a vortex alongside a diastolic jet signifies an
      efficient blood transport mechanism. Vortex formation time (VFT) is an index of
      the optimal conditions for vortex formation. It was hypothesized that left
      ventricular (LV) afterload impairs diastolic transmitral flow efficiency and
      therefore shifts the VFT out of its optimal range. METHODS: In 9 open-chest pigs,
      LV afterload was elevated by externally constricting the ascending aorta and
      increasing systolic blood pressure to 130% of baseline value for 3 minutes.
      RESULTS: Systolic LV function decreased, diastolic filling velocity increased
      only during the late (atrial) phase from 0.46 +/- 0.06 to 0.63 +/- 0.19 m/s (P =
      .0231), and end-diastolic LV volume and heart rate remained unchanged. VFT
      decreased from 4.09 +/- 0.27 to 2.78 +/- 1.03 (P = .0046). CONCLUSION: An acute,
      moderate elevation in LV afterload worsens conditions for diastolic vortex
      formation, suggesting impaired blood transport efficiency.

PMID- 19171462
TI  - The evidence provided by a single trial is less reliable than its statistical
      analysis suggests.
AB  - OBJECTIVE: To investigate whether a single trial can provide sufficiently robust
      evidence to warrant clinical implementation of its results. Trial-specific
      factors, such as subject selection, study design, and execution strategy, have an
      impact on the outcome of trials. In multiple trials, they may lead to
      heterogeneity that can be taken into account in the (random effects) meta
      analysis. Single trials lack this method of estimating the impact of such
      factors, and this affects the credibility of the results. STUDY DESIGN AND
      SETTING: To indicate how much the precision of the results of a single trial
      might be overestimated, we calculated the ratio of the widths of the confidence
      intervals when heterogeneity was taken into account and when it was not. RESULTS:
      The ratios of the widths of the confidence intervals with and without between
      study variability were 1.15, 1.41, and 2.00, when the heterogeneity I(2) values
      were 0.25, 0.50, and 0.75, respectively. CONCLUSION: The results of a single
      trial should be interpreted with caution. When it is difficult to predict or
      determine how trial-specific factors influence the results, the best way to
      evaluate the performance of a treatment is to use multiple, possibly smaller,
      trials.

PMID- 19171463
TI  - Neurolupus is associated with anti-ribosomal P protein antibodies: an inception
      cohort study.
AB  - OBJECTIVE: Serum IgG antibodies (Abs) to phosphorylated ribosomal (P ribosomal)
      proteins have been inconsistently associated with neuropsychiatric manifestations
      in systemic lupus erythematosus (SLE). Our aim was to assess whether serum IgG
      Abs to ribosomal P proteins are associated with neuropsychiatric SLE. PATIENTS
      AND METHODS: We examined an inception cohort of 219 SLE patients.
      Neuropsychiatric SLE manifestations were characterized using the American College
      of Rheumatology (ACR) definition. Serum Abs to P ribosomal proteins were searched
      for by immunoblotting. In a subgroup of patients, Abs were investigated also in
      cerebrospinal fluid (CSF). RESULTS: Abs to P ribosomal proteins were detected in
      45 (21%) patients, 23 of whom (51%) with neuropsychiatric involvement. Abs to P
      ribosomal protein were present both in serum and CSF. Abs to P ribosomal proteins
      significantly correlated with psychosis (p=0.017), mononeuropathy multiplex
      (p=0.040), malar rash (p=0.004), serum anti-Sm Abs (p=0.042), and lupus
      anticoagulant (p=0.036). SLE onset age was significantly younger in patients with
      Abs to P ribosomal proteins. Logistic regression analysis confirmed the
      relationship between Abs to P ribosomal proteins and psychosis, malar rash, SLE
      onset age and lupus anticoagulant. CONCLUSIONS: Abs to ribosomal P proteins are
      associated with psychosis and might be associated with peripheral nervous system
      complications.

PMID- 19171464
TI  - Schizophrenia model of elevated D2(High) receptors: haloperidol reverses the
      amphetamine-induced elevation in dopamine D2(High).

PMID- 19171465
TI  - Prevalence and risk of atopic disorders among schizophrenia patients: a
      nationwide population based study.
AB  - OBJECTIVE: Although a body of evidence indicates a link between psychiatric
      illnesses and allergies, no one has investigated the association between
      schizophrenia and atopic disorders. The objective of this nationwide population
      based study was to examine the prevalence and risk of atopic disorders (asthma,
      allergic rhinitis, urticaria, and atopic dermatitis) among schizophrenia
      patients. METHOD: This study used data from the Taiwan National Health Insurance
      Research Database covering the years 2000 to 2002. A total of 44,187 patients
      diagnosed with schizophrenia in the year 2000 were included, together with
      132,561 matched non-psychiatric controls. Follow up until the end of 2002
      identified concurrent diagnoses of atopic disorders. Logistic regression analyses
      were performed after controlling for the covariates of socio-demographic
      characteristics. RESULTS: Findings indicated high comorbidity, with 20.2% of
      schizophrenia patients (approximately one in five) experiencing concurrent atopic
      disorders. Moreover, schizophrenia in patients was independently associated with
      a 1.3-fold increased risk (95%CI=1.24-1.39) of concurrent asthma, after adjusting
      for socio-demographic characteristics. Yet the risk of diagnosed allergic
      rhinitis and urticaria was 23% (95%CI=0.74-0.81) and 26% (95%CI=0.72-0.77) lower,
      respectively, among schizophrenia patients compared to people without any
      psychiatric disease. CONCLUSION: Data suggests an increased risk of asthma and
      decreased risk of allergic rhinitis and urticaria among schizophrenia patients.
      Future studies on the identification of common etiologic pathways for
      schizophrenia and asthma could be significant for developing innovative
      treatments that target both illnesses concurrently.

PMID- 19171466
TI  - Follow-up MRI study of the insular cortex in first-episode psychosis and chronic
      schizophrenia.
AB  - Morphologic abnormalities of the insular cortex have been described in psychotic
      disorders such as schizophrenia, but it remains unknown whether these
      abnormalities develop progressively over the course of the illness. In the
      current study, longitudinal magnetic resonance imaging data were obtained from 23
      patients with first-episode psychosis (FEP), 11 patients with chronic
      schizophrenia, and 26 healthy controls. The volumes of the short (anterior) and
      long (posterior) insular cortices were measured on baseline and follow-up
      (between 1 and 4 years later) scans and were compared across groups. In cross
      sectional comparison at baseline, the FEP and chronic schizophrenia patients had
      significantly smaller short insular cortex than did controls. In longitudinal
      comparison, the FEP patients showed significant gray matter reduction of the
      insular cortex over time (-4.3%/2.0 years) compared with controls (0.3%/2.2
      years) without significant subregional effects, but there was no difference
      between chronic schizophrenia patients (-1.7%/2.4 years) and controls. The gray
      matter loss of the left insular cortex over time in FEP patients was correlated
      with the severity of positive and negative symptoms at follow-up. These findings
      indicate that patients with psychotic disorders have smaller gray matter volume
      of the insular cortex especially for its anterior portion (short insula) at first
      expression of overt psychosis, but also exhibit a regional progressive
      pathological process of the insular cortex during the early phase after the
      onset, which seems to reflect the subsequent symptomatology.

PMID- 19171467
TI  - Gamma-oryzanol-loaded calcium pectinate microparticles reinforced with chitosan:
      optimization and release characteristics.
AB  - Response surface methodology was used to optimize microparticle preparation
      conditions, including the ratio of pectin:gamma-oryzanol (OZ) (X(1)), agitation
      speed (X(2)), and the concentration of emulsifier (X(3)), for maximal entrapment
      efficiency (EE) of OZ-loaded Ca pectinate microparticles. The optimized values of
      X(1), X(2), and X(3) were found to be 2.72:5.28, 1143.5 rpm, and 2.61%,
      respectively. Experimental results obtained for the optimum formulation agreed
      favorably with the predicted results, indicating the usefulness of predicting
      models for EE. In order to evaluate the effect of chitosan-coating and blending
      on the release pattern of the entrapped OZ from microparticles, chitosan-coated
      and blended Ca pectinate microparticles were prepared. Release studies revealed
      that the chitosan treatments, especially the chitosan-coating, were effective in
      suppressing the release in both simulated gastric fluid (SGF) and intestinal
      fluid (SIF).

PMID- 19171468
TI  - [Intricated asthma tracheomalacia: diagnosis and therapeutic aspects].
AB  - An asthmatic girl was first hospitalized at age 2(9/12) years because of
      dyspnoea, lung consolidations and/or atelectasis, and rattling. Between ages
      2(9/12) and 6(2/12) years, she required three hospitalizations in ICU out of nine
      hospitalizations for the same symptoms. Differential diagnosis of this difficult
      to treat asthma disclosed severe tracheomalacia and persistent asthma. Treatments
      given according to the clinical, radiological and functional findings failed to
      decrease frequency and severity of acute respiratory episodes. Eventually,
      positive pressure ventilation delivered at airway opening (via a mouthpiece)
      associated to active respiratory physiotherapy succeeded in removing atelectasis
      and quickly cured the five following acute episodes without any further
      hospitalization. This case report is about diagnosis procedure, intricate asthma
      and tracheomalacia, and open mind to unusual therapeutics that may disclose
      potential help.

PMID- 19171469
TI  - Markers of inflammation, thrombosis and endothelial activation correlate with
      carotid IMT regression in stable coronary disease after atorvastatin treatment.
AB  - BACKGROUND AND AIMS: MIAMI is a prospective multicenter clinical study designed
      to investigate the relationship between changes in carotid intima-media thickness
      (C-IMT) and changes in circulating markers of inflammation, thrombosis and
      endothelial activation in stable coronary patients treated for 20+/-3.7 months
      with 20mg/day atorvastatin. METHODS AND RESULTS: Eighty-five subjects had their C
      IMT, blood lipids and soluble markers measured at baseline, at the 12th month and
      at the end of the study. Almost all soluble markers decreased upon treatment
      except for high-sensitivity C-reactive protein (hs-CRP), interleukin-18 (IL-18),
      tissue factor pathway inhibitor-free (TFPI-free) and soluble vascular cell
      adhesion molecules-1 (sVCAM-1) which did not change significantly, and
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and soluble CD40
      ligand (sCD40L) which increased. sCD40L, fibrinogen, tissue factor pathway
      inhibitor-total (TFPI-total), soluble intercellular adhesion molecules-1 (sICAM
      1), sE-selectin, interleukin-8 (IL-8) and von Willebrand factor (vWF) changed
      significantly even after application of the Bonferroni correction for multiple
      comparisons. Changes in lipids did not correlate with C-IMT regression either
      when considered singly or when combined in a lipid score. Changes in soluble
      markers correlated poorly with C-IMT regression when analyzed singly, but
      strongly when combined in relevant composite scores (inflammation/coagulation
      score, endothelial activation score, soluble markers score and total score).
      CONCLUSION: In patients with stable coronary artery disease treated with moderate
      doses of atorvastatin, carotid IMT regression correlated with changes of
      inflammation, thrombosis and endothelial activation profiles.

PMID- 19171470
TI  - From chronic overnutrition to insulin resistance: the role of fat-storing
      capacity and inflammation.
AB  - AIMS: We analyze how the inflammatory state in adipose tissue caused by a
      condition of chronically positive energy balance can lead to insulin resistance
      first in adipose tissue, then in all insulin-sensitive tissues. DATA SYNTHESIS:
      Chronic nutrient overload causes an increase in adipose depots that, if adipose
      tissue expandability is low, are characterized by an increased presence of
      hypertrophic adipocytes. This adipocyte hypertrophy is a possible stress
      condition for the endoplasmic reticulum (ER) that would lead to a proinflammatory
      state in adipose tissue. In this condition, ER stress would activate metabolic
      pathways that trigger insulin resistance, release of macrophage chemoattractant
      proteins, and in chronic inflammation, the death of the hypertrophic adipocyte.
      The infiltrated macrophages in turn release inflammatory proteins causing further
      recruitment of macrophages to adipose tissue and the release of inflammatory
      cytokines. Following these events, insulin resistance becomes extended to all
      adipose tissue. Insulin-resistant adipocytes, characterized by low liposynthetic
      capacity and high lipolytic capacity, cause increased release of free fatty acids
      (FFA). FFA released by lipolitic adipocytes may also activate Toll-like receptors
      4 and then chemokines and cytokines release amplifying insulin resistance,
      lipolysis and inflammation in all adipose tissue. Moreover, increased circulating
      FFA levels, reduced circulating adiponectin levels and leptin resistance lead to
      decreased lipid oxidation in non-adipose tissues, thereby triggering ectopic
      accumulation of lipids, lipotoxicity and insulin resistance. CONCLUSION: All the
      conditions that increase circulating fatty acids and cause lipid overloading
      (obesity, lipoatrophy, lipodystrophy, catabolic states, etc.) induce a lipotoxic
      state in non-adipose tissues that gives rise to insulin resistance.

PMID- 19171471
TI  - Omega-3 fatty acid supplementation decreases matrix metalloproteinase-9
      production in relapsing-remitting multiple sclerosis.
AB  - OBJECTIVES: The primary objective was to evaluate the effect of omega-3 fatty
      acids (omega-3 FA) on matrix metalloproteinase-9 (MMP-9) production by immune
      cells in multiple sclerosis (MS). Quality of life, fatty acid levels, and safety
      were also evaluated. MATERIALS AND METHODS: Ten participants with relapsing
      remitting MS (RRMS) received omega-3 FA supplementation (9.6g/day fish oil) in an
      open-label study. Participants were evaluated at four time points, baseline,
      after 1 month of omega-3 FA supplementation, after 3 months of omega-3 FA
      supplementation, and after a 3-month wash out. RESULTS: Immune cell secretion of
      MMP-9 decreased by 58% after 3 months of omega-3 FA supplementation when compared
      with baseline levels (p<0.01). This effect was coupled with a significant
      increase in omega-3 FA levels in red blood cell membranes. CONCLUSIONS: Omega-3
      FA significantly decreased MMP-9 levels in RRMS and may act as an immune
      modulator that has potential therapeutic benefit in MS patients.

PMID- 19171472
TI  - Mapping the experience of drug dealing risk environments: an ethnographic case
      study.
AB  - BACKGROUND: The traditional approach to understanding the economic dimensions of
      risk environments is to examine the forces that determine the activities of
      social actors. Drug dealing poses a particular problem for risk environments as
      dealing and drug dealers are often thought to be out of the scope of harm
      reduction interventions. However, local level drug dealing can be an important
      feature of local economies in marginalized communities, and the sharp
      distinctions between users and dealers may not always hold. METHODS: Ethnographic
      evidence is used to describe how two drug dealers experience risk. Two domestic
      spaces, the house of a heroin and amphetamine dealer respectively, are used to
      illustrate the relationships between structural forces, experience and physical
      space. RESULTS: One key mechanism through which risk environments mediate the
      relations between structural forces and individuals is through the modification
      of every day space. Rather than simply being a container for action, space is
      made through experience. This case study illustrates how two drug dealers orient
      themselves in space in relation to a complex amalgam of sensations, memories,
      inscriptions and intentions. Rather than simply being effects of structural
      oppression, these drug dealers are active participants in the local drug economy.
      The risk environment and associated economic processes become embodied into the
      dealers' and their physical environments. CONCLUSION: Drug dealers shape, and are
      shaped by, their risk environments. A 'determinants' approach to understanding
      the economic dimension to drug use risk environments needs to be refined.
      Community resilience policies such "neighbourhood renewal" need to take into
      account the embodied aspects of economic structures in the experience of drug use
      and drug dealing. The economic relations, the processes that disable the
      transformation of different forms of capital, the memories and the practices that
      make drug users, are embodied. Community resilience policies need to bring into
      focus the embodiment of the economic dimensions of risk environments if they are
      to successfully reduce harm.

PMID- 19171473
TI  - Comparing field investigations with laboratory models to predict landfill
      leachate emissions.
AB  - Investigations into laboratory reactors and landfills are used for simulating and
      predicting emissions from municipal solid waste landfills. We examined water flow
      and solute transport through the same waste body for different volumetric scales
      (laboratory experiment: 0.08 m(3), landfill: 80,000 m(3)), and assessed the
      differences in water flow and leachate emissions of chloride, total organic
      carbon and Kjeldahl nitrogen. The results indicate that, due to preferential
      pathways, the flow of water in field-scale landfills is less uniform than in
      laboratory reactors. Based on tracer experiments, it can be discerned that in
      laboratory-scale experiments around 40% of pore water participates in advective
      solute transport, whereas this fraction amounts to less than 0.2% in the
      investigated full-scale landfill. Consequences of the difference in water flow
      and moisture distribution are: (1) leachate emissions from full-scale landfills
      decrease faster than predicted by laboratory experiments, and (2) the stock of
      materials remaining in the landfill body, and thus the long-term emission
      potential, is likely to be underestimated by laboratory landfill simulations.

PMID- 19171474
TI  - Inexact fuzzy-stochastic constraint-softened programming - A case study for waste
      management.
AB  - In this study, an inexact fuzzy-stochastic constraint-softened programming method
      is developed for municipal solid waste (MSW) management under uncertainty. The
      developed method can deal with multiple uncertainties presented in terms of fuzzy
      sets, interval values and random variables. Moreover, a number of violation
      levels for the system constraints are allowed. This is realized through
      introduction of violation variables to soften system constraints, such that the
      model's decision space can be expanded under demanding conditions. This can help
      generate a range of decision alternatives under various conditions, allowing in
      depth analyses of tradeoffs among economic objective, satisfaction degree, and
      constraint-violation risk. The developed method is applied to a case study of
      planning a MSW management system. The uncertain and dynamic information can be
      incorporated within a multi-layer scenario tree; revised decisions are permitted
      in each time period based on the realized values of uncertain events. Solutions
      associated with different satisfaction degree levels have been generated,
      corresponding to different constraint-violation risks. They are useful for
      supporting decisions of waste flow allocation and system-capacity expansion
      within a multistage context.

PMID- 19171475
TI  - Sensing DNA-coatings of microparticles using micropipettes.
AB  - The resistive pulse technique is widely used to detect the size of small
      particles in aqueous solutions. This work demonstrates that a few tens of DNA
      molecules and thus the charges on a particle can be simply detected by pressure
      driven translocation through a microcapillary based Coulter counter. The typical
      opening of the capillaries ranges from 2 to 6 microm. The custom-built system
      gives optical access using a high numerical aperture objective allowing to
      observe colloids passing the sensing volume by optical means. We show the
      feasibility of our setup by distinguishing colloids with one and two micron
      diameters. Our measurements prove that a few ten strands of DNA bound to the
      colloids can be detected. This can be achieved by simple comparison of current
      amplitudes for blank and coated colloids at low salt concentrations (2-40 mmol
      [NaCl]). Our results clearly demonstrate that the Coulter counter can be used to
      detect the surface charges on colloids. Moreover, the results are in good
      agreement with a dynamical computer model taking into account the full geometry
      of the capillary.

PMID- 19171477
TI  - Effect of HIF-1 modulation on the response of two- and three-dimensional cultures
      of human colon cancer cells to 5-fluorouracil.
AB  - Tumour hypoxia represents a major obstacle to the success of radiotherapy and
      chemotherapy. The discovery that the hypoxia-inducible factor 1 (HIF-1) is a
      master regulator of cellular response to low oxygen led to the concept that
      inhibiting HIF-1 activity may sensitise hypoxic cancer cells to radiation and
      cytotoxic drugs. In the present study we investigate the effects of HIF-1
      modulation on the response of the human colon adenocarcinoma cell line HCT116 to
      5-fluorouracil (5FU). Increasing HIF-1 activity, either by exposing cells to
      hypoxia or by forced expression of a degradation-resistant form of HIF-1alpha,
      results in poor cell response to 5FU; conversely, knockdown of HIF-1alpha by RNA
      interference prevents hypoxia-induced resistance to 5FU. PMX290, a thioredoxin-1
      inhibitor, significantly inhibits HIF-1 activity and concomitantly sensitises
      hypoxic cells to 5FU. These results were confirmed in HCT116 cells grown as three
      dimensional spheroids, a model that more closely reproduces the hypoxic
      environment of solid tumours.

PMID- 19171479
TI  - Intramammary lymph node metastasis predicts poorer survival in breast cancer
      patients.
AB  - Involvement of an intramammary lymph node with metastatic breast cancer is an
      uncommon clinical or radiological presentation. Previously reported series of
      patients are small in number and the clinical advice is unclear. We identified
      100 patients on our pathology database with intramammary lymph nodes in
      association with a primary breast cancer. Ten were identified pre-operatively on
      breast imaging and 90 were first discovered on pathological assessment of excised
      breast tissue. Twenty one contained metastasis. Factors that predicted for
      intramammary node metastasis were increasing age (p=0.017), lymphovascular
      invasion (p=0.002) and grade of tumour (p=0.012). The presence of metastasis
      within the intramammary lymph node was associated with a poorer disease free
      survival (p=0.007) and reduced overall survival (p=0.035). Sixty seven percent of
      patients with intramammary node metastasis had further axillary metastases. One
      patient had an intramammary node metastasis but uninvolved axillary sentinel
      node. She presented 19 months later with an axillary nodal recurrence. The
      presence of intramammary lymph node metastasis is associated with poorer outcome
      in breast cancer patients. Pre-operative detection of intramammary lymph node
      metastasis is helpful to guide breast and axillary surgeries. Intramammary lymph
      node metastasis predicts strongly for axillary metastatic disease and axillary
      node clearance is recommended.

PMID- 19171478
TI  - Annexins in human breast cancer: Possible predictors of pathological response to
      neoadjuvant chemotherapy.
AB  - Neoadjuvant chemotherapy is used in women who have large or locally advanced
      breast cancers. However, up to 70% of women who receive neoadjuvant chemotherapy
      fail to achieve a complete pathological response in their primary tumour (a
      surrogate marker of long-term survival). Five proteins, previously identified to
      be linked with chemoresistance in our in vitro experiments, were identified
      histochemically in pre-treatment core needle biopsies from 40 women with large or
      locally advanced breast cancers. Immunohistochemical staining with the five
      proteins showed no single protein to be a predictor of response to chemotherapy.
      However, pre-treatment breast cancer specimens that were annexin-A2 positive but
      annexin-A1 negative correlated with a poor pathological response (p=0.04,
      Fisher's exact test). The mechanisms by which annexins confer chemoresistance
      have not been identified, but may be due to inhibition of apoptosis. Annexin-A1
      has been shown to enhance apoptosis, whilst annexin-A2, by contrast, inhibits
      apoptosis.

PMID- 19171476
TI  - EUROCARE-4. Survival of cancer patients diagnosed in 1995-1999. Results and
      commentary.
AB  - EUROCARE-4 analysed about three million adult cancer cases from 82 cancer
      registries in 23 European countries, diagnosed in 1995-1999 and followed to
      December 2003. For each cancer site, the mean European area-weighted observed and
      relative survival at 1-, 3-, and 5-years by age and sex are presented. Country
      specific 1- and 5-year relative survival is also shown, together with 5-year
      relative survival conditional to surviving 1-year. Within-country variation in
      survival is analysed for selected cancers. Survival for most solid cancers, whose
      prognosis depends largely on stage at diagnosis (breast, colorectum, stomach,
      skin melanoma), was highest in Finland, Sweden, Norway and Iceland, lower in the
      UK and Denmark, and lowest in the Czech Republic, Poland and Slovenia. France,
      Switzerland and Italy generally had high survival, slightly below that in the
      northern countries. There were between-region differences in the survival for
      haematologic malignancies, possibly due to differences in the availability of
      effective treatments. Survival of elderly patients was low probably due to
      advanced stage at diagnosis, comorbidities, difficult access or lack of
      availability of appropriate care. For all cancers, 5-year survival conditional to
      surviving 1-year was higher and varied less with region, than the overall
      relative survival.

PMID- 19171480
TI  - In situ microbial treatment of landfill leachate using aerated lagoons.
AB  - The aim of this study was to assess the efficiency of leachate treatment by
      microbial oxidation in four connected on-site aerated lagoons at a landfill site.
      The landfill site was found to be in an ageing methanogenic state, producing
      leachate with relatively low COD (mean value 1740 mg l(-1)) and relatively high
      ammonium concentrations (mean value 1241 mg l(-1)). Removal of COD averaged 75%,
      with retention times varying from 11 to 254 days. Overall 80% of the N load was
      removed within the plant, some by volatilisation of ammonium. Microbial community
      profiling of the water from each lagoon showed a divergent community profile,
      presumably a reflection of the nutrient status in each lagoon. In municipal solid
      waste landfills under similar conditions, leachate treatment through a
      facultative aerobic system in which sequential aerobic and anaerobic microbial
      oxidations occurred can readily be achieved using a simple two-lagoon system,
      suggesting this technology can be economic to install and simple to run.

PMID- 19171481
TI  - The bioleaching feasibility for Pb/Zn smelting slag and community characteristics
      of indigenous moderate-thermophilic bacteria.
AB  - The feasibility of recovering metal values and removing hazardous elements from
      the Pb/Zn smelting slag using bioleaching technique were studied through a flask
      experiment, and the community characteristics of the indigenous moderate
      thermophilic bacteria in this bioleaching system were also analyzed through a
      culture-independent restriction fragment length polymorphism (RFLP) of 16S rRNA
      genes approach. The results show that more than 80% of Al, As, Cu, Mn, Fe and Zn
      in the Pb/Zn smelting slag were leached at 65(o)C, pH 1.5, pulp density 5%, but
      only about 5% of Pb. Phylogenetic analysis revealed that the bacteria in the
      bioleaching system mainly fell among Firmicutes, Gammaproteobacteria and
      Betaproteobacteria, and the dominant bacteria are affiliated with Bacillus spp.,
      Sporosarcina spp. and Pseudomonas spp.

PMID- 19171482
TI  - Discovery of small molecule human C5a receptor antagonists.
AB  - A novel series of small molecule C5a antagonists is reported. In particular, in
      vitro metabolic studies and solution based combinatorial synthesis are
      demonstrated as useful tools for the rapid identification of antagonists with low
      in vitro clearance. Members of this series specifically inhibited the binding of
      (125)I-labeled C5a to human recombinant C5a receptor (C5aR). In functional cell
      assays these compounds displayed surmountable antagonism against C5a and did not
      demonstrate any detectable agonist activity.

PMID- 19171483
TI  - Time-dependent inactivation of human phenylethanolamine N-methyltransferase by 7
      isothiocyanatotetrahydroisoquinoline.
AB  - Inhibitors of phenylethanolamine N-methyltransferase [PNMT, the enzyme that
      catalyzes the final step in the biosynthesis of epinephrine (Epi)] may be of use
      in determining the role of Epi in the central nervous system. Here we describe
      the synthesis and characterization of 7-SCN tetrahydroisoquinoline as an affinity
      label for human PNMT.

PMID- 19171484
TI  - 1-Amido-1-phenyl-3-piperidinylbutanes - CCR5 antagonists for the treatment of
      HIV. Part 1.
AB  - The development of a new class of CCR5 antagonist replacing the tropane core of
      maraviroc by piperidine with a branched N-substituent is described. Compound 15h
      shows good whole cell antiviral activity together with microsomal stability and
      only weak activity at the hERG ion channel.

PMID- 19171485
TI  - Occlusive dressing of wounds: old tradition, new concepts.

PMID- 19171486
TI  - Ceramides: branched alkyl chains in the sphingolipid siblings of diacylglycerol
      improve biological potency.
AB  - The synthesis of a small number of ceramide analogues containing a combination of
      linear and highly branched alkyl chains on either the d-sphingosine or the N-acyl
      core of the molecule is reported. Regardless of location, the presence of the
      branched chain improves potency relative to the positive control, C2 ceramide;
      however, the most potent compound (4) has the branched side chain as part of the
      d-sphingosine core. The induction of apoptosis by 4 in terms of Annexin V binding
      and DiOC(6) labeling was superior to that achieved with C2 ceramide.

PMID- 19171487
TI  - Quantifying the architectural complexity of microscopic images of histology
      specimens.
AB  - Tumour grade (a measure of the degree of cellular differentiation of malignant
      neoplasm) is an important prognostic factor in many types of cancer. In general,
      poorly differentiated tumours are characterized by a higher degree of
      architectural irregularity and complexity of histological structures. Fractal
      dimension is a useful parameter for characterizing complex irregular structures.
      However, one of the difficulties of estimating the fractal dimension from
      microscopic images is the segmentation of pathologically relevant structures for
      analysis. A commonly used technique to segment structures of interest is to apply
      a pixel intensity threshold to convert the original image to binary and extract
      pixel outline structures from the binary representation. The difficulty with this
      approach is that the value of the threshold required to segment the histological
      structures is highly dependent on the staining technique chosen and imaging
      conditions (i.e., illumination time, intensity, and uniformity) of the
      microscopic system. In this work, we present a method for finding the optimal
      intensity threshold by maximizing the corresponding fractal dimension. This
      method results in the segmentation of histological structures and the estimation
      of their fractal dimension (independent of imaging conditions). We applied our
      technique to 164 prostate histology sections from 82 prostate core biopsy
      specimens (two serial sections from each of the 63 benign prostate tissues and 19
      high grade prostate carcinoma). We stained one of the serial sections with
      conventional hemotoxylin and eosin (H&E) and the other with pan-keratin, and
      found that the difference in mean fractal dimension between the two groups was
      statistically significant (p<0.0001) for both stains. However, using receiver
      operating characteristics (ROC) analysis, we conclude that our fractal dimension
      method applied to the images of pan-keratin stained sections provides greater
      classification performance (benign versus high grade) than with those stained
      with H&E when compared to the original histological diagnosis. The sensitivity
      and specificity achieved with the pan-keratin images were 89.5% and 90.5%,
      respectively.

PMID- 19171488
TI  - Relationship between radioactivity of radium and concentrations of barium and
      lead in hokutolite.
AB  - Hokutolite consists of barite (BaSO(4)) and anglesite (PbSO(4)), and contains
      significant amounts of radium isotopes as a radioactive mineral. Photon
      activation and gamma-ray spectrometry were employed to determine Ba, Pb and
      (226)Ra contents in hokutolite samples and to investigate the correlation between
      (226)Ra activity and both Ba and Pb content. (226)Ra activity in 30 hokutolite
      samples were estimated in the range of 40-65Bq/g and was positively related to Ba
      content (r=0.859, p<0.001), but independent of Pb content (r=-0.236, p=0.217).
      Experimental results implied that (226)Ra preferably precipitated with Ba over
      Pb. The (226)Ra activity in hokutolite from the Peitou Hot Spring was
      experimentally estimated based on the Ba/Pb ratio and expressed as (226)Ra
      (Bq/g)=14.67 (Ba/Pb)(molar)+14.13.

PMID- 19171489
TI  - Renal cell carcinoma with inferior vena cava thrombus: the Hacettepe experience.
AB  - OBJECTIVES: We evaluated the clinical outcome and factors affecting survival in
      patients with renal cell carcinoma (RCC) and tumor thrombus involving inferior
      vena cava (IVC). METHODS: Between 1990 and 2007, 28 patients with RCC and tumor
      thrombus extending into IVC underwent radical nephrectomy and thrombectomy.
      Patient data were reviewed retrospectively to evaluate the demographics, clinical
      presentation, surgical approach, pathological features, clinical outcomes, and
      survival. RESULTS: Twenty-eight patients with a mean age of 52.7 years were
      operated. Thrombus level was infrahepatic in 15 patients (54%), intrahepatic in 3
      patients (10%), suprahepatic in 3 patients (10%), supradiaphragmatic in 2
      patients (8%), and intracardiac in 5 patients (18%). All patients with
      intracardiac thrombi underwent cardiopulmonary bypass (CPB) and deep hypothermic
      circulatory arrest (DHCA). The mean tumor size was 98.21 mm. Four patients had
      distant metastases and 3 patients had lymph node involvement. Pathological
      examination revealed RCC of clear cell type in 26 patients, papillary in 1 and
      chromophobe in 1 patient. At a mean follow-up of 36.4 months, 16 patients were
      still alive while 8 patients died due to disease progression and 2 patients died
      of other causes. Two patients died of pulmonary emboli in the early postoperative
      period. Lymph node involvement, distant metastases, hypercalcemia, and
      sarcomatoid component were found to be factors affecting overall survival
      significantly. Level of tumor thrombus and Fuhrman grade did not affect survival.
      CONCLUSIONS: Radical nephrectomy and tumor thrombectomy is currently known to be
      the most effective method in patients with RCC and tumor thrombus extending into
      IVC. Factors affecting survival are the ones related to tumor biology. Tumor
      thrombus level does not affect the prognosis.

PMID- 19171490
TI  - Altered antioxidant status and lipid peroxidation in Indian patients with
      urothelial bladder carcinoma.
AB  - OBJECTIVES: Urothelial carcinoma of bladder is the second most common urological
      malignancy after prostate cancer. Recently, there has been increased interest in
      research of the role of free radicals and antioxidant materials in the
      prevention, treatment, and alleviation of therapy-related side effects of cancer.
      In the present study, we aimed to assess the alterations in the levels of
      antioxidant vitamins, activities of defense enzymes, circulating lipid peroxide,
      and total antioxidant activity (AOA) in patients with urothelial carcinoma of
      bladder and correlate these changes with the grade and severity of the disease.
      MATERIALS AND METHODS: The study cohort consisted of 90 subjects; 50 patients
      with bladder UC (25, low grade; 10, high grade; 15, muscle invasive) and 40
      healthy controls. Vitamins C and E, malondialdehyde (MDA), and AOA were estimated
      using standard protocols. Superoxide dismutase (SOD) and glutathione peroxidase
      (GPx) were assayed using commercially available kits. RESULTS: The serum levels
      of vitamins C and E, whole blood levels of SOD and GPx, and serum AOA was
      significantly lower (P < 0.001) while serum MDA levels were significantly higher
      (P < 0.001) in patients than in controls, indicating presence of oxidative stress
      in bladder UC patients. The levels of all the biochemical parameters were
      correlated with the grade and severity of the disease. There were significant
      differences between the patients with low grade tumors and muscle invasive tumors
      for all parameters (P < 0.001); except AOA (P < 0.279). CONCLUSIONS: The observed
      redox imbalance in UC of bladder in correlation with the grade and stage, as a
      consequence of decreased levels of antioxidant vitamins, enzymes, and AOA, along
      with increased MDA levels in circulation, may be important factors in tumor
      development and growth. Our results suggest that with advancing stage of bladder
      UC, the levels of oxidative stress increase, while levels of antioxidant
      molecules decrease. These findings suggest possible use of antioxidant
      supplementation as prophylactic agents for prevention and treatment of bladder
      cancer.

PMID- 19171491
TI  - Sequential intravesical gemcitabine and mitomycin C chemotherapy regimen in
      patients with non-muscle invasive bladder cancer.
AB  - OBJECTIVES: Currently, there are few options other than cystectomy for the
      management of BCG refractory non-muscle invasive bladder cancer. We report our
      experience with intravesical combination chemotherapy using gemcitabine and MMC
      in such patients. MATERIALS AND METHODS: We identified all patients with non
      muscle invasive bladder cancer who were BCG refractory or intolerant and had been
      treated with intravesical gemcitabine and MMC at our institution. Patients were
      treated with a combination of intravesical gemcitabine (1000 mg in 50 ml sterile
      water) followed sequentially by intravesical MMC (40 mg in 20 ml sterile water)
      every week for 6 weeks (induction). Induction therapy was followed by a
      maintenance regimen using the same dose of gemcitabine and MMC once a month for
      12 months. Data regarding patient demographics and disease information such as
      previous intravesical therapy, previous cystoscopy, cytology results, time to
      recurrence, and side effect profile were collected. RESULTS: A total of 10
      patients (6 male and 4 female) aged 48 to 85 years (median 67 years) underwent
      treatment with a median follow-up of 26.5 months (4-34 months). Six patients were
      recurrence free and have maintained their response at a median of 14 months (4-34
      months). Four patients had biopsy proven recurrence. Median time to recurrence
      was 6 months (range 4-13 months). The therapy was well tolerated in all patients.
      There were no major complications. Two patients experienced irritative lower
      urinary tract symptoms, which did not require cessation of therapy and one
      experienced a maculopapillary rash that improved with benadryl. CONCLUSIONS: In
      patients with recurrent BCG refractory bladder cancer, intravesical combination
      chemotherapy with gemcitabine and MMC appears to be well tolerated and yields a
      response in a good proportion number of patients.

PMID- 19171492
TI  - Indication, timing and results of endovascular treatment of type B dissection.
AB  - Aortic dissection is an uncommon but a highly lethal condition. Dissection of the
      ascending aorta is associated with a mortality rate of 1-2% per hour within the
      first 24h and should be managed by an open surgery. An uncomplicated, acute, type
      B dissection, which should be treated medically, is less frequently lethal, with
      survival rates of 84% within 1 year. Unfortunately, long-term outcome of medical
      therapy alone is suboptimal, with a reported 30-50% mortality rate at 5 years and
      a delayed expansion of the false lumen in 20-50% of patients at 4 years. In this
      setting, endovascular treatment should be considered when the aortic diameter
      exceeds 55-60mm, in case of uncontrolled pain, blood pressure and rapid growth of
      the dissecting aneurysm (>1cm per year). About 30-42% of acute, type B aortic
      dissections are complicated, as evidenced by haemodynamic instability or
      peripheral vascular ischaemia with a mortality rate of 50-85% if not treated
      properly. In this scenario, stent-graft repair is an attractive alternative to
      surgical repair for correcting ischaemic complications. The long-term therapy of
      patients with aortic dissection includes aggressive medical therapy, follow-up
      visits and serial imaging.

PMID- 19171493
TI  - Cold-induced limb pain decreases sensitivity to pressure-pain sensations in the
      ipsilateral forehead.
AB  - The aim of this study was to investigate the effect of unilateral limb pain on
      sensitivity to pain on each side of the forehead. In the first experiment,
      pressure-pain thresholds and sharpness sensations were assessed on each side of
      the forehead in 45 healthy volunteers before and after a 10 degrees C cold
      pressor of the hand and in 18 controls who were not subjected to the cold
      pressor. In a second experiment, forehead sensitivity was assessed in 32 healthy
      volunteers before and after a 2 degrees C cold pressor. The assessments were
      repeated without the cold pressor, and before and after six successive 4 degrees
      C cold pressor tests. The 10 degrees C cold pressor did not influence forehead
      sensitivity, whereas the 2 degrees C cold pressor and the 4 degrees C cold
      pressor tests resulted in bilateral analgesia to sharpness and pressure. The
      analgesia to pressure was greater in the ipsilateral forehead. Stress-induced
      analgesia and diffuse noxious inhibitory controls may have contributed to the
      analgesia to pressure-pain and sharpness sensations bilaterally after the most
      painful cold pressor tests. The locus coeruleus inhibits ipsilateral nociceptive
      activity in dorsal horn neurons during limb inflammation, and thus may have
      mediated the ipsilateral component of analgesia. Pain-evoked changes in forehead
      sensitivity differed for sharpness and pressure, possibly due to separate
      thalamic or cortical representations of cutaneous and deep tissue sensibility.
      These findings suggest that several mechanisms act concurrently to influence pain
      sensitivity at sites distant from a primary site of painful stimulation.

PMID- 19171494
TI  - Impairment of VGLUT2 but not VGLUT1 signaling reduces neuropathy-induced
      hypersensitivity.
AB  - Glutamate is the major excitatory neurotransmitter in the central nervous system
      with an important role in nociceptive processing. Storage of glutamate into
      vesicles is controlled by vesicular glutamate transporters (VGLUT). Null mutants
      for VGLUT1 and VGLUT2 were poorly viable, thus, pain-related behavior was
      presently compared between heterozygote VGLUT1 and VGLUT2 mice and their
      respective wild-type littermates using a test battery that included a variety of
      assays for thermal and mechanical acute nociception, and inflammatory and
      neuropathic pain syndromes. Behavioral analysis of VGLUT1 mutant mice did not
      show important behavioral changes in the pain conditions tested. Reduction of
      VGLUT2 also resulted in unaltered acute nociceptive and inflammatory-induced pain
      behavior. Interestingly, VGLUT2 heterozygote mice showed an attenuation or
      absence of some typical neuropathic pain features (e.g., absence of mechanical
      and cold allodynia after spared nerve injury). Chronic constriction injury in
      VGLUT2 heterozygote mice showed also reduced levels of cold allodynia, but had no
      impact on mechanical thresholds. Together, these data suggest that VGLUT2, but
      not VGLUT1, plays a role in neuropathy-induced allodynia and hypersensitivity,
      and might be a therapeutic target to prevent and/or treat neuropathic pain.

PMID- 19171495
TI  - T1 and T2 effects during radio-frequency pulses in spoiled gradient echo
      sequences.
AB  - Finite pulse durations in diverse pulse schemes lead to the reduction of the
      magnitude of the magnetization vector due to T(1) and T(2) effects during the
      radio-frequency pulses. This paper presents an analysis of the steady state
      signal in the presence of relaxation effects during radio-frequency pulses in MRI
      spoiled gradient echo sequences. It is shown that minor attenuations of the
      magnetization vector can have dramatic consequences on the measured signal, and
      may thus entail a loss in SNR benefits at high static magnetic fields if a
      careful analysis is not performed. It is emphasized that it is the time
      integrated magnetization vector trajectory that matters for these effects and not
      only the pulse duration. Some experimental results obtained on a phantom at 3T
      verify this analysis.

PMID- 19171496
TI  - Nonlinear ultrasonic waves in bubbly liquids with nonhomogeneous bubble
      distribution: Numerical experiments.
AB  - This paper deals with the nonlinear propagation of ultrasonic waves in mixtures
      of air bubbles in water, but for which the bubble distribution is nonhomogeneous.
      The problem is modelled by means of a set of differential equations which
      describes the coupling of the acoustic field and bubbles vibration, and solved in
      the time domain via the use and adaptation of the SNOW-BL code. The attenuation
      and nonlinear effects are assumed to be due to the bubbles exclusively. The
      nonhomogeneity of the bubble distribution is introduced by the presence of bubble
      layers (or clouds) which can act as acoustic screens, and alters the behaviour of
      the ultrasonic waves. The effect of the spatial distribution of bubbles on the
      nonlinearity of the acoustic field is analyzed. Depending on the bubble density,
      dimension, shape, and position of the layers, its effects on the acoustic field
      change. Effects such as shielding and resonance of the bubbly layers are
      especially studied. The numerical experiments are carried out in two
      configurations: linear and nonlinear, i.e. for low and high excitation pressure
      amplitude, respectively, and the features of the phenomenon are compared. The
      parameters of the medium are chosen such as to reproduce air bubbly water
      involved in the stable cavitation process.

PMID- 19171497
TI  - Performance in the cranio-cervical flexion test is altered in elderly subjects.
AB  - The cranio-cervical flexion test (CCFT) tests the coordination of the deep and
      superficial cervical flexor muscles during a cranio-cervical flexion task. The
      test has revealed impairments in muscle function in younger/middle aged patients
      with various neck pain disorders. Neck pain and headache are common in elders but
      it is unknown if age alone affects performance in the CCFT. This study compared
      performance in the CCFT between healthy asymptomatic elderly and younger
      subjects. Electromyographic (EMG) amplitude in the sternocleidomastoid (SCM),
      angle of cranio-cervical flexion and ability to target the pressure levels of
      each test stage were examined in 44 elderly and 39 young participants. The
      results indicated that the elderly group had higher measures of normalized EMG
      signal amplitude in the SCM during the test (p<0.001), greater shortfalls from
      the target pressures of all stages of the test (p<0.01), except for the 22 mm Hg
      stage (p=0.13), and larger variability of the cranio-cervical flexion range of
      motion for the five successive stages of the test (particularly at 26, 28 and 30
      mm Hg stages) compared to young subjects. Clinicians must be aware of this
      occurrence when assessing performance in the CCFT in elders with neck pain.

PMID- 19171499
TI  - Human polyomaviruses, WU and KI in HIV exposed children with acute lower
      respiratory tract infections in hospitals in South Africa.
AB  - BACKGROUND: The importance of two recently identified polyomaviruses, WUV and
      KIV, as respiratory pathogens in populations with a high HIV prevalence needs to
      be defined, since human polyomaviruses can cause significant morbidity and
      mortality in patients with immunosuppression. Geographic distribution and disease
      association of WUV and KIV genotypes are not yet clearly defined. OBJECTIVES: To
      investigate the prevalence of WUV and KIV in HIV-positive and HIV-negative
      patients with respiratory infections in hospitals in South Africa and determine
      their genotypes. STUDY DESIGN: Specimens from patients with acute respiratory
      infections from hospitals serving Pretoria were screened for WUV and KIV.
      Positive specimens were sequenced and subjected to phylogenetic analysis.
      RESULTS: WUV was identified in (7%) and KIV in (1%) of mainly pediatric patients.
      Co-infections were common in WUV- and KIV-infected patients (71% and 66.6%,
      respectively); 57% of patients with WUV and 33% of patients with KIV were HIV
      positive while the HIV prevalence in the respiratory virus patient group screened
      in this study was 33% WUV and KIV patients presented with moderate to severe
      lower respiratory tract disease. Four distinct and 2 unique WUV strains were
      identified clustering into 2 of 4 globally identified genotypes. KIV strains were
      identical to strains from Sweden. CONCLUSION: WUV is frequently detected in HIV
      infected patients with respiratory disease, but its role as respiratory pathogen
      remains uncertain.

PMID- 19171500
TI  - A dose-ranging study of pramipexole for the symptomatic treatment of restless
      legs syndrome: polysomnographic evaluation of periodic leg movements and sleep
      disturbance.
AB  - OBJECTIVE: To evaluate, both polysomnographically and by subjective scales, the
      efficacy and safety profile of pramipexole for restless legs syndrome (RLS) via a
      3-week, double-blind, placebo-controlled, parallel-group, dose-ranging study.
      METHODS: At baseline and after 3 weeks, periodic limb movements (PLM) and sleep
      parameters were assessed by polysomnography, and patients self-assessed their
      sleep disturbance and overall RLS severity using the international RLS study
      group rating scale (IRLS). Four pramipexole doses were evaluated: 0.125, 0.25,
      0.50, and 0.75mg/d. Data from 107 patients were included in the intent-to-treat
      (ITT) analysis. RESULTS: For pramipexole recipients, the primary outcome measure,
      PLM per hour in bed asleep or awake (the PLM index, or PLMI), decreased by a
      median of -26.55 to -52.70 depending on dosage group, vs. -3.00 for placebo
      (p<0.01 or 0.001 for each group vs. placebo; Wilcoxon-Mann-Whitney test).
      Improvements in the secondary endpoints of PLM while asleep and while awake were
      also significantly superior for pramipexole. At 3 weeks, all pramipexole doses
      reduced the median for PLM while asleep to levels considered normal (<5PLM/h).
      Except for delta-sleep time and awakenings/arousals, sleep parameters remained
      unchanged or favored pramipexole. Median sleep latency was reduced by -5.00 to 
      11.75min in the pramipexole groups, vs. -2.00 for placebo (p<0.05 for all groups
      except 0.25mg/d). Median total sleep time increased by 25.75-66.75min, vs. 25.50
      (p<0.05 for 0.50mg/d), and median time in stages 2-4/rapid eye movement (REM)
      sleep increased by 37.00-68.00min, vs. 26.75 (p<0.05 for 0.50mg/d). By subjective
      IRLS ratings, all pramipexole doses were significantly superior to placebo.
      Safety analysis demonstrated no dose-dependent increase in adverse events, and no
      drug-related increase in daytime somnolence was observed. CONCLUSIONS:
      Pramipexole is effective and well tolerated in RLS, most notably among objective
      measures, for reducing PLM and decreasing sleep latency. Although other sleep
      parameters showed lesser, usually insignificant change, patients' subjective
      ratings of RLS severity and sleep disturbance were significantly improved
      (p0.0023).

PMID- 19171502
TI  - Contraception for adolescents.
AB  - Ensuring that sexually active adolescents are using contraception consistently
      and correctly is an effective means of reducing unplanned pregnancy. Use of
      highly effective long-acting reversible methods, such as subdermal implants, is
      low. We need to challenge the perception that the pill and condoms, the most
      commonly used contraceptive methods, are always the most suitable methods for
      young people. Changes in adolescent sexual behaviour, including increased number
      of sexual partners, is consistent with a rise in sexually transmitted infections.
      No contraceptive methods, with the exception of male or female sterilisation, are
      contra-indicated solely on the grounds of age. Young people need to be counselled
      about both the benefits and risks associated with each method so that they can
      make an informed choice. Most of the clinical evidence on contraceptive use comes
      from studies of 'older' women, with little research identified that specifically
      addressed implications for adolescent contraceptive use.

PMID- 19171501
TI  - Modulation of dendritic cells using granulocyte-macrophage colony-stimulating
      factor (GM-CSF) delays type 1 diabetes by enhancing CD4+CD25+ regulatory T cell
      function.
AB  - Abnormalities in DC function are implicated in defective immune regulation that
      leads to type-1 diabetes (T1D) in NOD mice and humans. In this study, we used GM
      CSF and Flt3-L to modulate DC function in NOD mice and observed the effects on
      T1D development. Treatment with either ligand at earlier stages of insulitis
      suppressed the development of T1D. Unlike Flt3-L, GM-CSF was more effective in
      suppressing T1D, even when administered at later stages of insulitis. In vitro
      studies and in vivo adoptive transfer experiments revealed that CD4+CD25+ T cells
      from GM-CSF-treated mice could suppress effector T cell response and T1D. This
      suppression is likely mediated through enhanced IL-10 and TGF-beta1 production.
      Adoptive transfer of GM-CSF exposed DCs to naive mice resulted in an expansion of
      Foxp3+ T cells and a significant delay in T1D onset. Our results indicate that GM
      CSF acted primarily on DCs and caused an expansion of Foxp3+ Tregs which delayed
      the onset of T1D in NOD mice.

PMID- 19171503
TI  - Relationship between scalp potential and autonomic nervous activity during a
      mental arithmetic task.
AB  - The cerebral cortex had massive bidirectional connections to autonomic nervous
      system and mental performance can induce change of autonomic activity, but which
      regions are related to autonomic function is not clear. The study was to analyze
      the scalp positions which may affect cardiac autonomic nervous activity during a
      mental arithmetic (MA) task. Forty-three healthy male subjects were voluntarily
      participated in the study. Sympathetic and parasympathetic activities were
      estimated with heart rate variability. Scalp potential was determined by the
      wavelet packet parameters and approximate entropy (ApEn) of Electroencephalogram
      (EEG). The results showed that heart rate and the normalized low frequency power
      component were significantly increased (p<0.01) and the high frequency power
      component was decreased (p<0.01). Meanwhile relative wavelet packet energy in
      alpha band of EEG at P3, P4, Pz, O1, O2 and Oz electrodes were decreased and the
      beta band of EEG at the same electrodes were increased significantly (p<0.01).
      ApEn was significantly increased in MA (p<0.01). Moreover, changes of brain
      activity were earlier than the changes of autonomic activity and significantly
      correlations existed between heart rate variability and wavelet packet energy
      (p<0.05). In addition, a significant positive correlation between HR change and
      the laterality ratio score of alpha band in P3 v P4 (p<0.05) were observed. It is
      noted that cerebral conscious activity enhanced with the decrease of
      parasympathetic activity and increase of sympathetic activity, and the right post
      central areas dominated sympathetic activity during stress-inducing mental tasks.

PMID- 19171505
TI  - Use of Total Error concept in the validation of viral activity in cell cultures.
AB  - Due to the high variability inherent of experimental recipients, validating
      biological methods is often a complex exercise, and following ICH Q2R1
      recommendations is not always feasible and/or meaningful. Linking systematic
      error and random error to obtain a unique criterion, as defined in ISO guideline,
      could be of interest to capture the total variability in biological assays. In
      this paper, the use of Total Error concept in the validation of biological assays
      was for the first time investigated and compared to a conventional interpretation
      of the ICH guideline. Both decision methodologies concluded that the assay was
      valid from 2.13 to 5.83 log(10)(CCID(50)/ml). However, only the Total Error
      approach using accuracy profile as decision tool allowed to guarantee that
      accurate and reliable results will be obtained during the future routine
      application of the assay. In addition, the risk to obtain out of acceptance
      limits results was estimated using this approach and was found out to be at the
      most 3.1% irrespective of the concentration level, thus demonstrating the
      reliability of the biological assay.

PMID- 19171504
TI  - Lipidomic analysis of endocannabinoid metabolism in biological samples.
AB  - The endocannabinoids are signaling lipids present in many living organisms. They
      activate G protein-coupled cannabinoid receptors to modulate a broad range of
      biological processes that include emotion, cognition, inflammation and
      reproduction. The endocannabinoids are embedded in an interconnected network of
      cellular lipid pathways, the regulation of which is likely to control the
      strength and duration of endocannabinoid signals. Therefore, physiopathological
      or pharmacological perturbations of these pathways may indirectly affect
      endocannabinoid activity and, vice versa, endocannabinoid activity may influence
      lipid pathways involved in other metabolic and signaling events. Recent progress
      in liquid chromatography and mass spectrometry has fueled the development of
      targeted lipidomic approaches, which allow researchers to examine complex lipid
      interactions in cells and gain a broader view of the endocannabinoid system.
      Here, we review these new developments from the perspective of our laboratory's
      experience in the field.

PMID- 19171507
TI  - Radio-guided occult lesion localization versus wire-guided localization in non
      palpable breast lesions.
AB  - 'Radio-guided occult lesion localization' is a new technique in the breast
      conservative surgery performed for the localization and resection of non-palpable
      breast lesions. The purpose of this study is to evaluate the results of this
      breast surgical procedure provided by several published papers.

PMID- 19171506
TI  - Photo-crosslinked poly(epsilon-caprolactone fumarate) networks for guided
      peripheral nerve regeneration: material properties and preliminary biological
      evaluations.
AB  - In an effort to achieve suitable biomaterials for peripheral nerve regeneration,
      we present a material design strategy of combining a crystallite-based physical
      network and a crosslink-based chemical network. Biodegradable polymer disks and
      conduits have been fabricated by photo-crosslinking three poly(epsilon
      caprolactone fumarate)s (PCLF530, PCLF1250, and PCLF2000), which were synthesized
      from the precursor poly(epsilon-caprolactone) (PCL) diols with nominal molecular
      weights of 530, 1250, and 2000 g mol(-1), respectively. Thermal properties such
      as glass transition temperature (T(g)), melting temperature (T(m)), and
      crystallinity of photo-crosslinked PCLFs were examined and correlated with their
      rheological and mechanical properties. Furthermore, in vitro degradation of
      uncrosslinked and crosslinked PCLFs in PBS crosslinked PCLFs in 1 N NaOH aqueous
      solution at 37 degrees C was studied. In vitro cytocompatibility, attachment, and
      proliferation of Schwann cell precursor line SPL201 cells on three PCLF networks
      were investigated. Crosslinked PCLF2000 with the highest crystallinity and
      mechanical properties was found to best support cell attachment and
      proliferation. Using a new photo-crosslinking method, single-lumen crosslinked
      PCLF nerve conduits without defects were fabricated in a glass mold. Crosslinked
      PCLF2000 nerve conduits were selected for evaluation in a 1cm gap rat sciatic
      nerve model. Histological evaluation demonstrated that the material was
      biocompatible with sufficient strength to hold sutures in place after 6 and 17
      weeks of implantation. Nerve cable with myelinated axons was found in the
      crosslinked PCLF2000 nerve conduit.

PMID- 19171509
TI  - A rare case of facial dermatofibrosarcoma protuberans and its reconstructive
      challenges.

PMID- 19171510
TI  - The healing of critical-sized bone defect of rat zygomatic arch with particulate
      bone graft and bone morphogenetic protein-2.
AB  - For some critical-sized bony defects in the facial bones, it is necessary that
      the defect be reconstructed using an autologous bone graft from another donor
      site, not only to ensure stability, but also to derive aesthetic contouring.
      However, because of the easy gain and easy moulding of particulate bone, it would
      be easier to reconstruct the defect by using particulate bone graft (PBG) rather
      than block bone graft (BBG). This study was designed to confirm the usefulness of
      PBG with bone morphogenetic protein-2 (BMP-2) instead of BBG and to observe its
      long-term outcome in critical-sized zygomatic arch defects in a rat model. A
      sample of 18 Sprague-Dawley rats was divided into three groups; a 5-mm critical
      sized bone defect was made in both zygomatic arches of all subjects. Each group
      was treated with different combinations of BMP-2 and PBG. At 2, 4, 8 and 12 weeks
      after treatment, each defect was compared radiologically. Histological evaluation
      was performed after 12 weeks. In the first group, the defects with PBG decreased
      more than in those with no bone graft (P<0.01). In the second group, defects with
      PBG and BMP-2 decreased more than in those with PBG alone (P<0.01). In the third
      group, there was no significant difference between the group with PBG and BMP-2
      and that with in situ bone graft (instead of BBG). In conclusion, PBG with BMP-2
      showed satisfactory bone healing without any additional bone graft in the animal
      model.

PMID- 19171511
TI  - Hemi aplasia of the nose with complete cleft lip and palate of the contralateral
      side.
AB  - Nasal aplasia, including hemi aplasia of the nose, is a rare congenital anomaly
      of the nose. Since the ipsilateral side tends to be affected more frequently than
      the contralateral side of the face in half nose anomalies, only reports
      concerning the ipsilateral defect are numerous. This report presents an unusual
      case of hemi aplasia of the nose with complete cleft lip and palate of the
      contralateral side. A local flap on the nasal dorsum was used for nasal
      reconstruction, where correction of the elongation of the inner canthal distance
      and the shape of the inner canthus was performed.

PMID- 19171512
TI  - Improved event interval reconstruction in synthetic electrocardiograms.
AB  - Mathematical models for synthesizing ECGs are important tools in providing
      reproducible standard signals for biomedical signal processing research and
      technology. The ECG synthesis model ECGsyn and its extensions are the state of
      the art and realistically capture: 1) the ECG morphology; 2) the spectrum of
      heart rate variability; and 3) QT-interval adaptation to heart rate. This paper
      demonstrates ECGsyn's time-domain limitations at reconstructing an ECG time
      series from ECG wave annotations. An alternative algorithm, ECGfm, is therefore
      presented that recreates the event intervals with greater fidelity by applying
      the wave annotations as a phase constraint. Results on data drawn from the
      Physionet Physobank QT database demonstrate the improved performance of the ECGfm
      algorithm.

PMID- 19171513
TI  - Improving ECG beats delineation with an evolutionary optimization process.
AB  - As in other complex signal processing tasks, ECG beat delineation algorithms are
      usually constituted of a set of processing modules, each one characterized by a
      certain number of parameters (filter cutoff frequencies, threshold levels, time
      windows, etc.). It is well recognized that the adjustment of these parameters is
      a complex task that is traditionally performed empirically and manually, based on
      the experience of the designer. In this paper, we propose a new automated and
      quantitative method to optimize the parameters of such complex signal processing
      algorithms. To solve this multiobjective optimization problem, an evolutionary
      algorithm (EA) is proposed. This method for parameter optimization is applied to
      a wavelet-transform-based ECG delineator that has previously shown interesting
      performance. An evaluation of the final delineator, using the optimal parameters,
      has been performed on the QT database from Physionet and results are compared
      with previous algorithms reported in the literature. The optimized parameters
      provide a more accurate delineation, with a global improvement of 7.7%, over all
      the criteria evaluated, and over the best results found in the literature, which
      is a proof of interest in the approach.

PMID- 19171514
TI  - Segmentation of dual-axis swallowing accelerometry signals in healthy subjects
      with analysis of anthropometric effects on duration of swallowing activities.
AB  - Dysphagia (swallowing difficulty) is a serious and debilitating condition that
      often accompanies stroke, acquired brain injury, and neurodegenerative illnesses.
      Individuals with dysphagia are prone to aspiration (the entry of foreign material
      into the airway), which directly increases the risk of serious respiratory
      consequences such as pneumonia. Swallowing accelerometry is a promising
      noninvasive tool for the detection of aspiration and the evaluation of
      swallowing. In this paper, dual-axis accelerometry was implemented since the
      motion of the hyolaryngeal complex occurs in both anterior-posterior and superior
      inferior directions during swallowing. Dual-axis cervical accelerometry signals
      were acquired from 408 healthy subjects during dry, wet, and wet chin tuck
      swallowing tasks. The proposed segmentation algorithm is based on the idea of
      sequential fuzzy partitioning of the signal and is well suited for long signals
      with nonstationary variance. The algorithm was validated with simulated signals
      with known swallowing locations and a subset of 295 real swallows manually
      segmented by an experienced speech language pathologist. In both cases, the
      algorithm extracted individual swallows with over 90% accuracy. The time duration
      analysis was carried out with respect to gender, body mass index (BMI), and age.
      Demographic and anthropometric variables influenced the duration of these
      segmented signals. Male participants exhibited longer swallows than female
      participants (p=0.05). Older participants and participants with higher BMIs
      exhibited swallows with significantly longer (p=0.05) duration than younger
      participants and those with lower BMIs, respectively.

PMID- 19171515
TI  - Recognition of abstract objects via neural oscillators: interaction among
      topological organization, associative memory and gamma band synchronization.
AB  - Synchronization of neural activity in the gamma band is assumed to play a
      significant role not only in perceptual processing, but also in higher cognitive
      functions. Here, we propose a neural network of Wilson-Cowan oscillators to
      simulate recognition of abstract objects, each represented as a collection of
      four features. Features are ordered in topological maps of oscillators connected
      via excitatory lateral synapses, to implement a similarity principle. Experience
      on previous objects is stored in long-range synapses connecting the different
      topological maps, and trained via timing dependent Hebbian learning (previous
      knowledge principle). Finally, a downstream decision network detects the presence
      of a reliable object representation, when all features are oscillating in
      synchrony. Simulations performed giving various simultaneous objects to the
      network (from 1 to 4), with some missing and/or modified properties suggest that
      the network can reconstruct objects, and segment them from the other
      simultaneously present objects, even in case of deteriorated information, noise,
      and moderate correlation among the inputs (one common feature). The balance
      between sensitivity and specificity depends on the strength of the Hebbian
      learning. Achieving a correct reconstruction in all cases, however, requires ad
      hoc selection of the oscillation frequency. The model represents an attempt to
      investigate the interactions among topological maps, autoassociative memory, and
      gamma-band synchronization, for recognition of abstract objects.

PMID- 19171516
TI  - Directly manipulated free-form deformation image registration.
AB  - Previous contributions to both the research and open source software communities
      detailed a generalization of a fast scalar field fitting technique for cubic B
      splines based on the work originally proposed by Lee . One advantage of our
      proposed generalized B-spline fitting approach is its immediate application to a
      class of nonrigid registration techniques frequently employed in medical image
      analysis. Specifically, these registration techniques fall under the rubric of
      free-form deformation (FFD) approaches in which the object to be registered is
      embedded within a B-spline object. The deformation of the B-spline object
      describes the transformation of the image registration solution. Representative
      of this class of techniques, and often cited within the relevant community, is
      the formulation of Rueckert who employed cubic splines with normalized mutual
      information to study breast deformation. Similar techniques from various groups
      provided incremental novelty in the form of disparate explicit regularization
      terms, as well as the employment of various image metrics and tailored
      optimization methods. For several algorithms, the underlying gradient-based
      optimization retained the essential characteristics of Rueckert's original
      contribution. The contribution which we provide in this paper is two-fold: 1) the
      observation that the generic FFD framework is intrinsically susceptible to
      problematic energy topographies and 2) that the standard gradient used in FFD
      image registration can be modified to a well-understood preconditioned form which
      substantially improves performance. This is demonstrated with theoretical
      discussion and comparative evaluation experimentation.

PMID- 19171517
TI  - Rate-distortion efficient piecewise planar 3-D scene representation from 2-D
      images.
AB  - In any practical application of the 2-D-to-3-D conversion that involves storage
      and transmission, representation efficiency has an undisputable importance that
      is not reflected in the attention the topic received. In order to address this
      problem, a novel algorithm, which yields efficient 3-D representations in the
      rate distortion sense, is proposed. The algorithm utilizes two views of a scene
      to build a mesh-based representation incrementally, via adding new vertices,
      while minimizing a distortion measure. The experimental results indicate that, in
      scenes that can be approximated by planes, the proposed algorithm is superior to
      the dense depth map and, in some practical situations, to the block motion vector
      based representations in the rate-distortion sense.

PMID- 19171519
TI  - Enabling location privacy and medical data encryption in patient telemonitoring
      systems.
AB  - Patient telemonitoring systems (PTS) deal with the acquisition, processing, and
      secure transmission of a patient's physiological and physical parameters to a
      remote location, where expert medical knowledge is available. In emergency
      situations, when the patient's life is threatened, the trend in modern PTS is to
      transmit the current location of the patient. Although research in communications
      security has led to mechanisms that sufficiently protect medical data, research
      related to location privacy area is still in its early stages. This paper
      proposes an architecture that enhances PTS through location privacy and data
      encryption. We study the most popular PTS technologies in conjunction with
      location privacy architectures and propose an innovative scheme that exploits a
      point-to-point protocol called Mist. We describe a prototype implementation,
      developed for validating the proposed framework along with the corresponding
      evaluation results.

PMID- 19171520
TI  - Real-time 3-D ultrasound scan conversion using a multicore processor.
AB  - Real-time 3-D ultrasound scan conversion (SC) in software has not been practical
      due to its high computation and I/O data handling requirements. In this paper, we
      describe software-based 3-D SC with high volume rates using a multicore
      processor, Cell. We have implemented both 3-D SC approaches: 1) the separable 3-D
      SC where two 2-D coordinate transformations in orthogonal planes are performed in
      sequence and 2) the direct 3-D SC where the coordinate transformation is directly
      handled in 3-D. One Cell processor can scan-convert a 192 x 192 x 192 16-bit
      volume at 87.8 volumes/s with the separable 3-D SC algorithm and 28 volumes/s
      with the direct 3-D SC algorithm.

PMID- 19171521
TI  - Aggregation of classifiers for staining pattern recognition in antinuclear
      autoantibodies analysis.
AB  - Indirect immunofluorescence is currently the recommended method for the detection
      of antinuclear autoantibodies (ANA). The diagnosis consists of both estimating
      the fluorescence intensity and reporting the staining pattern for positive wells
      only. Since resources and adequately trained personnel are not always available
      for these tasks, an evident medical demand is the development of computer-aided
      diagnosis (CAD) tools that can support the physician decisions. In this paper, we
      present a system that classifies the staining pattern of positive wells on the
      strength of the recognition of their cells. The core of the CAD is a multiple
      expert system (MES) based on the one-per-class approach devised to label the
      pattern of single cells. It employs a hybrid approach since each composing binary
      module is constituted by an ensemble of classifiers combined by a fusion rule.
      Each expert uses a set of stable and effective features selected from a wide pool
      of statistical and spectral measurements. In this framework, we present a novel
      parameter that measures the reliability of the final classification provided by
      the MES. This feature is used to introduce a reject option that allows to reduce
      the error rate in the recognition of the staining pattern of the whole well. The
      approach has been evaluated on 37 wells, for a total of 573 cells. The measured
      performance shows a low overall error rate ( 2.7%-5.8%), which is below the
      observed intralaboratory variability.

PMID- 19171522
TI  - Real-time analysis of physiological data to support medical applications.
AB  - This paper presents a flexible framework that performs real-time analysis of
      physiological data to monitor people's health conditions in any context (e.g.,
      during daily activities, in hospital environments). Given historical
      physiological data, different behavioral models tailored to specific conditions
      (e.g., a particular disease, a specific patient) are automatically learnt. A
      suitable model for the currently monitored patient is exploited in the real-time
      stream classification phase. The framework has been designed to perform both
      instantaneous evaluation and stream analysis over a sliding time window. To allow
      ubiquitous monitoring, real-time analysis could also be executed on mobile
      devices. As a case study, the framework has been validated in the intensive care
      scenario. Experimental validation, performed on 64 patients affected by different
      critical illnesses, demonstrates the effectiveness and the flexibility of the
      proposed framework in detecting different severity levels of monitored people's
      clinical situations.

PMID- 19171523
TI  - Detection of movement in bed using unobtrusive load cell sensors.
AB  - Quality of sleep is an important attribute of an individual's health state and
      its assessment is therefore a useful diagnostic feature. Changes in the patterns
      of motor activities during sleep can be a disease marker, or can reflect various
      abnormal physiological and neurological conditions. Presently, there are no
      convenient, unobtrusive ways to assess quality of sleep outside of a clinic. This
      paper describes a system for unobtrusive detection of movement in bed that uses
      load cells installed at the corners of a bed. The system focuses on identifying
      when a movement occurs based on the forces sensed by the load cells. The movement
      detection approach estimates the energy in each load cell signal over short
      segments to capture the variations caused by movement. The accuracy of the
      detector is evaluated using data collected in the laboratory. The detector is
      capable of detecting voluntary movements in bed while the subjects were awake,
      with an average equal error rate of 3.22% (+/-0.54). Its performance is invariant
      with respect to the individual's characteristics, e.g., weight, as well as those
      of the bed. The simplicity of the resulting algorithms and their relative
      insensitivity to the weight and height of the monitored individual make the
      approach practical and easily deployable in residential and clinical settings.

PMID- 19171524
TI  - Integrating heterogeneous classifier ensembles for EMG signal decomposition based
      on classifier agreement.
AB  - In this paper, we present a design methodology for integrating heterogeneous
      classifier ensembles by employing a diversity-based hybrid classifier fusion
      approach, whose aggregator module consists of two classifier combiners, to
      achieve an improved classification performance for motor unit potential
      classification during electromyographic (EMG) signal decomposition. Following the
      so-called overproduce and choose strategy to classifier ensemble combination, the
      developed system allows the construction of a large set of base classifiers, and
      then automatically chooses subsets of classifiers to form candidate classifier
      ensembles for each combiner. The system exploits kappa statistic diversity
      measure to design classifier teams through estimating the level of agreement
      between base classifier outputs. The pool of base classifiers consists of
      different kinds of classifiers: the adaptive certainty-based, the adaptive fuzzy
      k -NN, and the adaptive matched template filter classifiers; and utilizes
      different types of features. Performance of the developed system was evaluated
      using real and simulated EMG signals, and was compared with the performance of
      the constituent base classifiers. Across the EMG signal datasets used, the
      developed system had better average classification performance overall,
      especially in terms of reducing classification errors. For simulated signals of
      varying intensity, the developed system had an average correct classification
      rate CCr of 93.8% and an error rate Er of 2.2% compared to 93.6% and 3.2%,
      respectively, for the best base classifier in the ensemble. For simulated signals
      with varying amounts of shape and/or firing pattern variability, the developed
      system had a CCr of 89.1% with an Er of 4.7% compared to 86.3% and 5.6%,
      respectively, for the best classifier. For real signals, the developed system had
      a CCr of 89.4% with an Er of 3.9% compared to 84.6% and 7.1%, respectively, for
      the best classifier.

PMID- 19171525
TI  - A semantically enriched clinical guideline model enabling deployment in
      heterogeneous healthcare environments.
AB  - Clinical guidelines are developed to assist healthcare practitioners to make
      decisions on patient's medical problems, and as such they communicate with
      external applications to retrieve patient data to initiate medical actions
      through clinical workflows, and transmit information to alert/reminder systems.
      The interoperability problems in the healthcare information technology domain
      prevent wider deployment of clinical guidelines because each deployment requires
      a tedious custom adaptation phase. In this paper, we provide machine-processable
      mechanisms that express the semantics of clinical guideline interfaces so that
      automated processes can be used to access the clinical resources for guideline
      deployment and execution. To be able to deploy the semantically extended
      guidelines to healthcare settings semiautomatically, the underlying application's
      semantics must also be available. We describe how this can be achieved based on
      two prominent implementation technologies in use in the eHealth domain:
      integrating healthcare enterprise cross-enterprise document sharing integration
      profile for discovering and exchanging electronic healthcare records and Web
      service technology for interacting with the clinical workflows and wireless
      medical sensor devices. The system described in this paper is realized within the
      scope of the SAPHIRE Project.

PMID- 19171526
TI  - Modeling interaction for segmentation of neighboring structures.
AB  - This paper presents a new method for segmenting medical images by modeling
      interaction between neighboring structures. Compared to previously reported
      methods, the proposed approach enables simultaneous segmentation of multiple
      neighboring structures for improved robustness. During the segmentation process,
      the object contour evolution and shape prior estimates are influenced by the
      interactions between neighboring shapes consisting of attraction, repulsion, and
      competition. Instead of estimating the a priori shape of each structure
      independently, an interactive maximum a posteriori shape estimation method is
      used for estimating the shape priors by considering shape prior distribution,
      neighboring shapes, and image features. Energy functionals are then formulated to
      model the interaction and segmentation. With the proposed method, neighboring
      structures with similar intensities and/or textures, and blurred boundaries can
      be extracted simultaneously. Experimental results obtained on both synthetic data
      and medical images demonstrate that the introduced interaction between
      neighboring structures improves segmentation performance compared with other
      existing approaches.

PMID- 19171527
TI  - Computer-aided detection and diagnosis of breast cancer with mammography: recent
      advances.
AB  - Breast cancer is the second-most common and leading cause of cancer death among
      women. It has become a major health issue in the world over the past 50 years,
      and its incidence has increased in recent years. Early detection is an effective
      way to diagnose and manage breast cancer. Computer-aided detection or diagnosis
      (CAD) systems can play a key role in the early detection of breast cancer and can
      reduce the death rate among women with breast cancer. The purpose of this paper
      is to provide an overview of recent advances in the development of CAD systems
      and related techniques. We begin with a brief introduction to some basic concepts
      related to breast cancer detection and diagnosis. We then focus on key CAD
      techniques developed recently for breast cancer, including detection of
      calcifications, detection of masses, detection of architectural distortion,
      detection of bilateral asymmetry, image enhancement, and image retrieval.

PMID- 19171528
TI  - Indexes for three-class classification performance assessment--an empirical
      comparison.
AB  - Assessment of classifier performance is critical for fair comparison of methods,
      including considering alternative models or parameters during system design. The
      assessment must not only provide meaningful data on the classifier efficacy, but
      it must do so in a concise and clear manner. For two-class classification
      problems, receiver operating characteristic analysis provides a clear and concise
      assessment methodology for reporting performance and comparing competing systems.
      However, many other important biomedical questions cannot be posed as "two-class"
      classification tasks and more than two classes are often necessary. While several
      methods have been proposed for assessing the performance of classifiers for such
      multiclass problems, none has been widely accepted. The purpose of this paper is
      to critically review methods that have been proposed for assessing multiclass
      classifiers. A number of these methods provide a classifier performance index
      called the volume under surface (VUS). Empirical comparisons are carried out
      using 4 three-class case studies, in which three popular classification
      techniques are evaluated with these methods. Since the same classifier was
      assessed using multiple performance indexes, it is possible to gain insight into
      the relative strengths and weakness of the measures. We conclude that: 1) the
      method proposed by Scurfield provides the most detailed description of classifier
      performance and insight about the sources of error in a given classification task
      and 2) the methods proposed by He and Nakas also have great practical utility as
      they provide both the VUS and an estimate of the variance of the VUS. These
      estimates can be used to statistically compare two classification algorithms.

PMID- 19171529
TI  - Cardiac motion recovery via active trajectory field models.
AB  - Cardiovascular researchers are constantly developing new and innovative medical
      imaging technologies, striving to improve the understanding, diagnosis, and
      treatment of cardiovascular dysfunction. Combining these sophisticated imaging
      methods with advancements in image understanding via computational intelligence
      will continue to advance the frontier of cardiovascular medicine. Recently,
      researchers have turned to a new class of tissue motion imaging techniques,
      including displacement encoding with stimulated echoes (DENSE) in cardiac
      magnetic resonance (cMR) imaging, to directly quantify cardiac displacement and
      produce accurate spatiotemporal measurements of myocardial strain, twist, and
      torsion. The associated analysis of DENSE cMR and other tissue motion imagery,
      however, represents a major bottleneck in the study of intramyocardial mechanics.
      In the computational intelligence area of deformable models, this paper develops
      an automated motion recovery technique termed active trajectory field models
      (ATFMs) geared toward these new motion imaging protocols, offering quantitative
      physiological measurements without the pains of manual analyses. This novel
      generative deformable model exploits both image information and prior knowledge
      of cardiac motion, utilizing a point distribution model derived from a training
      set of myocardial trajectory fields to automatically recover cardiac motion from
      a noisy image sequence. The effectiveness of the ATFM method is demonstrated by
      quantifying myocardial motion in 2-D short-axis murine DENSE cMR image sequences
      both before and after myocardial infarction, producing results comparable to
      existing semiautomatic analysis methods.

PMID- 19171530
TI  - PathMiner: a Web-based tool for computer-assisted diagnostics in pathology.
AB  - Large-scale, multisite collaboration has become indispensable for a wide range of
      research and clinical activities that rely on the capacity of individuals to
      dynamically acquire, share, and assess images and correlated data. In this paper,
      we report the development of a Web-based system, PathMiner , for interactive
      telemedicine, intelligent archiving, and automated decision support in pathology.
      The PathMiner system supports network-based submission of queries and can
      automatically locate and retrieve digitized pathology specimens along with
      correlated molecular studies of cases from "ground-truth" databases that exhibit
      spectral and spatial profiles consistent with a given query image. The
      statistically most probable diagnosis is provided to the individual who is
      seeking decision support. To test the system under real-case scenarios, a
      pipeline infrastructure was developed and a network-based test laboratory was
      established at strategic sites at the University of Medicine and Dentistry of New
      Jersey-Robert Wood Johnson Medical School, Robert Wood Johnson University
      Hospital, the University of Pennsylvania School of Medicine, Hospital of the
      University of Pennsylvania, The Cancer Institute of New Jersey, and Rutgers
      University. The average five-class classification accuracy of the system was
      93.18% based on a tenfold cross validation on a close dataset containing 3691
      imaged specimens. We also conducted prospective performance studies with the
      PathMiner system in real applications in which the specimens exhibited large
      variations in staining characters compared with the training data. The average
      five-class classification accuracy in this open-set experiment was 87.22%. We
      also provide the comparative results with the previous literature and the
      PathMiner system shows superior performance.

PMID- 19171531
TI  - Enhancement of multichannel chromosome classification using a region-based
      classifier and vector median filtering.
AB  - Multichannel chromosome image acquisition is used for cancer diagnosis and
      research on genetic disorders. This type of imaging, apart from aiding the
      cytogeneticist in several ways, facilitates the visual detection of chromosome
      abnormalities. However, chromosome misclassification errors result from different
      factors, such as uneven hybridization, spectral overlap among fluors, and
      biochemical noise. In this paper, we enhance the chromosome classification
      accuracy by making use of a region Bayes classifier that increases the
      classification accuracy when compared to the already developed pixel-by-pixel
      classifier and by incorporating the vector median filtering approach for
      filtering of the image. The method is evaluated using a publicly available
      database that contains 183 six-channel chromosome sets of images. The overall
      improvement on the chromosome classification accuracy is 9.99%, compared to the
      pixel-by-pixel classifier without filtering. This improvement in the chromosome
      classification accuracy would allow subtle deoxyribonucleic acid abnormalities to
      be identified easily. The efficiency of the method might further improve by using
      features extracted from each region and a more sophisticated classifier.

PMID- 19171532
TI  - Recurrent metastatic tuberculous gummata with a unique para-spinal tuberculous
      abscess.

PMID- 19171533
TI  - Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis.

PMID- 19171534
TI  - Allergic contact dermatitis from timolol complicating choroidal melanoma-related
      glaucoma.

PMID- 19171535
TI  - Unilateral angiokeratoma of the breast.

PMID- 19171536
TI  - Unusual cutaneous presentation of ALK+ anaplastic large cell lymphoma mimicking
      syphilis on the glans penis.

PMID- 19171537
TI  - Eruptive pseudoangiomatosis.

PMID- 19171538
TI  - Chronic eczema in a patient with Leukocyte Adhesion Deficiency (LAD) type I.

PMID- 19171539
TI  - Extranodal NK/T-cell lymphoma, nasal type presenting as a pyogenic granuloma-like
      on a fingertip.

PMID- 19171540
TI  - Adult-onset Stills disease with a cellulitis-like eruption.

PMID- 19171541
TI  - Apocrine hidrocystoma on the finger.

PMID- 19171542
TI  - Acquired progressive lymphangioma with atypical clinical presentation.

PMID- 19171543
TI  - Pemphigoid nodularis: the importance of ELISA for diagnosis.

PMID- 19171544
TI  - Eosinophilic annular erythema responsive to chloroquin.

PMID- 19171545
TI  - Nodular fasciitis of the upper eyelid.

PMID- 19171546
TI  - Cutaneous metastasis of post-irradiation osteosarcoma.

PMID- 19171547
TI  - Sweets syndrome: a rare first cutaneous diagnostic sign in cervical cancer.

PMID- 19171548
TI  - Granulomatous slack skin clinically and histologically masquerading as borderline
      leprosy in its early stages.

PMID- 19171549
TI  - Guidelines on the use of high-dose intravenous immunoglobulin in dermatology.
AB  - The treatment recommendations presented for the use of IVIg in dermatology
      highlight the high status of IVIg therapy in numerous defined dermatological
      autoimmune diseases and in toxic epidermal necrolysis. The high value of IVIg
      therapy in diseases which are otherwise refractory to treatment is undisputed. A
      clear case therefore exists for making a treatment recommendation such as
      described above for the conditions mentioned. Because the mechanism of action of
      IVIG in vivo is still unclear, however, further efforts should be made to reach
      standard therapies for the affected patient groups. This would enable even larger
      case series conducted by different therapists at different sites to be evaluated.
      Orientation towards the guideline recommendations laid down here should create a
      basis for this. The implementation of this EU guideline in general practice means
      that the use of IVIg in dermatology will be optimized throughout Europe.

PMID- 19171550
TI  - Fatty acid 2-hydroxylase regulates cAMP-induced cell cycle exit in D6P2T
      schwannoma cells.
AB  - Sphingolipids are ubiquitous components of eukaryotic cells that regulate various
      cellular functions. In many cell types, a fraction of sphingolipids contain 2
      hydroxy fatty acids, produced by fatty acid 2-hydroxylase (FA2H), as the N-acyl
      chain of ceramide [hydroxyl fatty acid (hFA)-sphingolipids]. FA2H is highly
      expressed in myelin-forming cells of the nervous system and in epidermal
      keratinocytes. While hFA-sphingolipids are thought to enhance the physical
      stability of specialized membranes produced by these cells, physiological
      significance of hFA-sphingolipids in many other cell types is unknown. In this
      study, we report novel roles for FA2H and hFA-sphingolipids in the regulation of
      the cell cycle. Treatment of D6P2T Schwannoma cells with dibutyryl-cAMP (db-cAMP)
      induced exit from the cell cycle with concomitant upregulation of FA2H. Partial
      silencing of FA2H in D6P2T cells resulted in 60-70% reduction of hFA
      dihydroceramide and hFA-ceramide, with no effect on nonhydroxy dihydroceramide
      and ceramide. Under these conditions, db-cAMP no longer induced cell cycle exit,
      and cells continued to grow and divide. Immunoblot analyses revealed that FA2H
      silencing prevented db-cAMP-induced upregulation of cyclin-dependent kinase
      inhibitors p21 and p27. These results provide evidence that FA2H is a negative
      regulator of the cell cycle and facilitates db-cAMP-induced cell cycle exit in
      D6P2T cells.

PMID- 19171551
TI  - Rapid infusion rituximab changing practice for patient care.
AB  - Rituximab is a chimeric anti-CD20 monoclonal antibody. Its intravenous
      administration is associated with substantial infusion related-toxicity.
      Recommended infusion durations are prolonged (average 5-6 h for first infusion
      and 3-4 h for subsequent infusions). We aimed to explore the safety and
      tolerability of short infusion rituximab, (over 90 min), in Non-Hodgkin's
      lymphoma patients at Riyadh Military Hospital. Adult oncology patients diagnosed
      with Non-Hodgkin's lymphoma, who were to receive rituximab, were included in the
      study. The schedule of administration for cycle one was unaltered and delivered
      according to the product monograph (5-6 h). All subsequent cycles were
      administered over a total infusion time of 90 min (20% of the dose in the first
      30 min then the remaining 80% over 60 min, total dose delivered in 500 mL sodium
      chloride). All patients were observed for infusion related reactions during the
      rituximab infusion and for 30 min after the infusion. In addition, all patients
      were advised to report any reaction occurring within 24 h after rituximab
      infusion.From April 2007 to September 2007, 21 patients with non-Hodgkin's
      lymphoma were treated with rituximab-based chemotherapy. A total of 126 infusions
      were administered with average of 6 infusions per patient. The majority of
      patients were treated with CHOP-Rituximab or CHOP-like regimen. The 90-min
      Rituximab infusion schedule was well tolerated with no grade 3/4 infusion related
      adverse events observed. A rapid infusion rituximab over 90 min is well tolerated
      and safe when administered as the second and subsequent infusions in the course
      of therapy. This shortened infusion schedule has resulted in a substantial
      reduction in resource utilization. Our institution has adopted this as routine
      practice.

PMID- 19171552
TI  - Nail toxicity induced by cancer chemotherapy.
AB  - PURPOSE: To provide a comprehensive literature review of chemotherapy-induced
      nail toxicity, including clinical presentation, implicated drugs and approaches
      for prevention and management. DATA SOURCE: A search of MEDLINE and EMBASE (1966
      2008) databases was conducted using the terms (and variations of the terms)
      antineoplastic agents, nails, nail toxicity, onycholysis, and paronychia.
      Bibliographies from selected articles were reviewed for appropriate references.
      DATA EXTRACTION: The retrieved literature was reviewed to include all articles
      relevant to the clinical presentation, diagnosis, incidence, prevention, and
      treatment of chemotherapy-induced nail toxicity. DATA SYNTHESIS: Nail toxicity is
      a relatively uncommon adverse effect linked to a number of chemotherapeutic
      agents. Clinical presentation varies, depending on which nail structure is
      affected and the severity of the insult. Nail changes may involve all or some
      nails. Toxicity may be asymptomatic and limited to cosmetic concerns, however,
      more severe effects, involving pain and discomfort can occur. Taxanes and
      anthracyclines are the antineoplastic drug groups most commonly implicated. It is
      suggested that the administration schedule may influence the incidence of nail
      abnormalities, for example reported cases linked to the weekly administration of
      paclitaxel.Before instituting chemotherapy, patients should be educated regarding
      potential nail toxicities and strategies for prevention implemented. Management
      includes appropriate nail cutting, avoiding potential irritants, topical, or oral
      antimicrobials, and possibly cessation or dose reduction of the offending agent.
      Cryotherapy, through the application of frozen gloves or socks, has been
      beneficial in reducing docetaxel-induced nail toxicity and may be effective for
      other drugs.

PMID- 19171553
TI  - The optimal therapeutic use of ixabepilone in patients with locally advanced or
      metastatic breast cancer.
AB  - BACKGROUND: The epothilones are a new class of microtubule-stabilizing drugs that
      exert potent antitumor activity against taxane-resistant and multidrug resistant
      cell lines. The most clinically advanced member of this class is the
      semisynthetic epothilone B derivative ixabepilone. PURPOSE: This article reviews
      the preclinical and clinical data on ixabepilone in patients with locally
      advanced and metastatic breast cancer (MBC) and provides guidance for pharmacists
      on its optimal use. DATA SOURCE: PubMed and conference proceedings through August
      2008. RESULTS: In preclinical studies, ixabepilone has demonstrated potent
      antitumor activity and low susceptibility to mechanisms that confer tumor
      resistance. Clinically meaningful benefits have been achieved with ixabepilone
      monotherapy in phase 2 trials of patients with MBC who have failed previous
      chemotherapies (anthracyclines, taxanes, or capecitabine). In a randomized, phase
      3 trial, the combination of ixabepilone and capecitabine proved more effective
      than capecitabine alone after the failure of taxane and anthracycline regimens.
      At the recommended dose and schedule, the therapeutic ratio of ixabepilone is
      generally favorable, and its adverse effects (notably neutropenia and peripheral
      neuropathy) are generally manageable and reversible. CONCLUSION: Ixabepilone
      represents an advance in the treatment of anthracycline - and taxane-pretreated
      MBC. Future studies will define its efficacy in combination with other drugs used
      in the treatment of MBC, as well as in other types of cancer.

PMID- 19171554
TI  - Antineoplastic agent workplace contamination study: the Alberta Cancer Board
      Pharmacy perspective Phase III.
AB  - OBJECTIVE: To continue with workplace contamination monitoring in the Alberta
      Cancer Board (ACB) pharmacy practice environment. SETTING: The ACB in the
      Canadian province of Alberta which includes two public tertiary centers and 19
      associated community satellite sites based around the province in existing
      hospitals. METHODS: After the completion of a Phase 1 and Phase 11 study,(1)
      which investigated the feasibility of routine monitoring of antineoplastic agent
      contamination in the pharmacy practice environment, it was decided to launch a
      Phase III study. The Phase III study would be done at the Cross Cancer Institute
      in the main pharmacy department as well as at a brand new satellite pharmacy
      within the CCI hospital. Samples would be taken in these areas as well as on the
      outer exterior of latex gloves worn to prepare cyclophosphamide and other
      antineoplastics. RESULTS: The result determined that the area in front of the
      biological safety cabinet in the main CCI pharmacy department as well as the
      exterior of the latex gloves showed evidence of cyclophosphamide contamination.
      The results from the sample taken in the new satellite pharmacy showed no
      evidence of cyclophosphamide contamination. CONCLUSION: results from this study
      prompted a decision to launch a Phase IV study to determine the feasibility
      within our network, for routine monitoring as well as sampling throughout the
      clean room beyond the BSC.

PMID- 19171555
TI  - Patients' perspectives and safe handling of oral anticancer drugs at an Asian
      cancer center.
AB  - Background. In view of the increased usage of oral anticancer drugs in the
      contemporary treatment of cancer, we aimed to examine cancer patients'
      perspectives of oral anticancer drugs, through a survey at an Asian cancer
      centre. This study also intended to describe patients' behavior regarding
      storage, handling, and administration of oral anticancer drugs. METHODS: This
      cross sectional survey was conducted at a single site. The interviewer
      administered survey was undertaken at the outpatient pharmacy of National Cancer
      Centre Singapore (NCCS), the largest ambulatory cancer center in Singapore,
      between January and March 2008. Eligible patients had received at least one cycle
      of oral anticancer agent treatment or had been taking oral anticancer agents
      continuously for 3 months. RESULTS: A total of 126 patients were surveyed. Median
      age of surveyed patients was 58 years (range 31-85 years). The drugs involved
      were capecitabine (39.7% of patients), tamoxifen (23.1%), aromatase inhibitors
      (18.2%), gefitinib (9.1%), and imatinib (3.3%). Over 90% patients self
      administered their oral anticancer drugs. The majority of the patients (94.2%)
      reported no difficulties in adherence to their oral anticancer treatment
      regimens. Forty per cent of patients reported habitually washing their hands
      after administering their anticancer drugs. None of the patients, except two
      patients receiving capecitabine, indicated that they habitually used gloves to
      handle their oral anticancer medications. CONCLUSION: The majority of patients
      receiving oral anticancer agents reported no difficulty in adhering to their oral
      anticancer treatment regimens as prescribed. However, this survey demonstrated
      the need to improve patients' understanding of the requirements for storage,
      handling and safe administration of oral anticancer drugs.

PMID- 19171557
TI  - Celebrities help promote campaign to destigmatise mental illness.

PMID- 19171558
TI  - Experts call for patient safety in preregistration training to be explicit.

PMID- 19171559
TI  - Middle classes in Britain drink most alcohol, but smoking is at lowest recorded
      level.

PMID- 19171560
TI  - HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity.

PMID- 19171561
TI  - Should NICE's threshold range for cost per QALY be raised? Yes.

PMID- 19171562
TI  - Should NICE's threshold range for cost per QALY be raised? No.

PMID- 19171563
TI  - MPs criticise UK government's science adviser for stance on homoeopathy.

PMID- 19171566
TI  - Peripheral administration of GH induces cell proliferation in the brain of adult
      hypophysectomized rats.
AB  - IGF-I treatment has been shown to enhance cell genesis in the brains of adult GH-
      and IGF-I-deficient rodents; however, the influence of GH therapy remains poorly
      understood. The present study investigated the effects of peripheral recombinant
      bovine GH (bGH) on cellular proliferation and survival in the neurogenic regions
      (subventricular zone (SVZ), and dentate gyrus of the hippocampus), as well as the
      corpus callosum, striatum, parietal cortex, and piriform cortex. Hypopituitarism
      was induced in female rats by hypophysectomy, and the rats were supplemented with
      thyroxine and cortisone acetate. Subsequently, the rats received daily s.c.
      injections of bGH for either 6 or 28 days respectively. Following 5 days of
      peripheral bGH administration, the number of bromodeoxyuridine (BrdU)-positive
      cells was increased in the hippocampus, striatum, parietal cortex, and piriform
      cortex after 6 and 28 days. In the SVZ, however, BrdU-positive cells increased
      only after 28 days of bGH treatment. No significant change was observed in the
      corpus callosum. In the hippocampus, after 28 days of bGH treatment, the number
      of BrdU/NeuN-positive cells was increased proportionally to increase the number
      of BrdU-positive cells. (3)H-thymidine incorporation in vitro revealed that 24 h
      of bGH exposure was sufficient to increase cell proliferation in adult
      hippocampal progenitor cells. This study shows for the first time that 1)
      peripheral bGH treatment increased the number of newborn cells in the adult brain
      and 2) bGH exerted a direct proliferative effect on neuronal progenitor cells in
      vitro.

PMID- 19171564
TI  - Long term survival after evidence based treatment of acute myocardial infarction
      and revascularisation: follow-up of population based Perth MONICA cohort, 1984
      2005.
AB  - OBJECTIVE: To examine trends in long term survival in patients alive 28 days
      after myocardial infarction and the impact of evidence based medical treatments
      and coronary revascularisation during or near the event. DESIGN: Population based
      cohort with 12 year follow-up. SETTING: Perth, Australia. PARTICIPANTS: 4451
      consecutive patients with a definite acute myocardial infarction according to the
      World Health Organization MONICA (monitoring trends and determinants in
      cardiovascular disease) criteria admitted to hospital during 1984-7, 1988-90, and
      1991-3. MAIN OUTCOME MEASURES: All cause mortality identified from official
      mortality records and the hospital morbidity data, with death from cardiovascular
      disease as a secondary end point. RESULTS: In the 1991-3 cohort, 28 day survivors
      of acute myocardial infarction had a 7.6% absolute event reduction (95%
      confidence interval 4% to 11%) or a 28% lower relative risk reduction (16% to
      38%), unadjusted for risk of death, over 12 years after the incident admission
      compared with the 1984-7 cohort, similar to the survival of the 1988-90 cohort.
      The improved survival for the 1991-3 cohort persisted after adjustment for
      demographic factors, coronary risk factors, severity of disease, and event
      complications with an adjusted relative risk reduction of 26% (14% to 37%), but
      this was not apparent after further adjustment for medical treatments in hospital
      and coronary revascularisation procedures within 12 months of the incident
      myocardial infarction. CONCLUSION: The improving trends in 12 year survival after
      a definite acute myocardial infarction are associated with progressive use of
      evidence based treatments during the initial admission to hospital and in the 12
      months after the event. These changes in the management of acute myocardial
      infarction are probably contributing to the continuing decline in mortality from
      coronary heart disease in Australia.

PMID- 19171567
TI  - Human fetal pancreatic insulin-producing cells proliferate in vitro.
AB  - There have been considerable efforts towards understanding the potential of human
      pancreatic endocrine cells to proliferate and transition into mesenchymal cell
      populations. Since rodent studies have demonstrated that mouse insulin-producing
      cells do not proliferate in vitro, a similar possibility has been considered for
      human islet endocrine cells. Considering the inherent differences in mouse and
      human pancreatic islets, we decided to assess the potential of human fetal
      pancreatic insulin-producing cells to proliferate in vitro. We studied the
      proliferative potential of human fetal pancreatic islet-derived populations from
      second or third trimester fetal pancreas and characterized the cells that grow
      out during their expansion. We have used seven different approaches including in
      situ hybridization and immunostaining, quantitative estimation of multiple gene
      transcripts in populations as well as in single cells, clonal analysis of islet
      cells, assessment of heritable marks of active insulin promoter, and thymidine
      analog-based lineage tracing. Our studies demonstrate that human fetal pancreatic
      insulin-producing cells proliferate in vitro to generate mesenchymal cell
      populations. Interestingly, epigenetic modifications that mark open chromatin
      conformation of insulin promoter regions are retained even after a million fold
      expansion/proliferation in vitro. These findings demonstrate that hormone
      producing cells in pancreatic islets proliferate in vitro and retain epigenetic
      marks that characterize an active insulin promoter. Such in vitro-derived
      mesenchymal cells may be of potential use in cell-replacement therapy for
      diabetes.

PMID- 19171568
TI  - Effect of cell phone distraction on pediatric pedestrian injury risk.
AB  - OBJECTIVE: Early adolescents are using cell phones with increasing frequency.
      Cell phones are known to distract motor vehicle drivers to the point that their
      safety is jeopardized, but it is unclear if cell phones might also distract child
      pedestrians. This study was designed to examine the influence of talking on a
      cell phone for pediatric pedestrian injury risk. PARTICIPANTS AND METHODS:
      Seventy-seven children aged 10 to 11 years old completed simulated road crossings
      in an immersive, interactive virtual pedestrian environment. In a within-subjects
      design, children crossed the virtual street 6 times while undistracted and 6
      times while distracted by a cell phone conversation with an unfamiliar research
      assistant. Participants also completed several other experimental tasks
      hypothesized to predict the impact of distraction while crossing the street and
      talking on a cell phone. RESULTS: Children's pedestrian safety was compromised
      when distracted by a cell phone conversation. While distracted, children were
      less attentive to traffic; left less safe time between their crossing and the
      next arriving vehicle; experienced more collisions and close calls with oncoming
      traffic; and waited longer before beginning to cross the street. Analyses testing
      experience using a cell phone and experience as a pedestrian yielded few
      significant results, suggesting that distraction on the cell phone might affect
      children's pedestrian safety no matter what their experience level. There was
      some indication that younger children and children who are less attentive and
      more oppositional may be slightly more susceptible to distraction while talking
      on the cell phone than older, more attentive, and less oppositional children.
      CONCLUSION: Our results suggest that cell phones distract preadolescent children
      while crossing streets.

PMID- 19171569
TI  - Impact of the 2004-2005 influenza vaccine shortage on pediatric practice: a
      national survey.
AB  - BACKGROUND: A severe influenza vaccine shortage occurred during the 2004-2005
      influenza season because of the loss of all vaccine made by Chiron (Emeryville,
      CA) for US distribution. OBJECTIVES: The objectives of this study were to assess
      among pediatricians nationally: (1) influenza vaccine-delivery strategies; (2)
      reported vaccine shortages and factors associated with experiencing shortages;
      and (3) the impact of shortages on vaccine redistribution, patient referral, and
      clinical practice, including patient prioritization. METHODS: A survey was
      administered in March 2005 through June 2005 to 427 pediatricians who
      participated in a national network representative of the American Academy of
      Pediatrics membership. RESULTS. Our response rate was 82%. Thirty-nine percent of
      the pediatricians had a computerized method for identifying patients at high risk
      needing vaccination. Ninety-four percent and 79% reported giving high-priority to
      children >/=24 months old with high-risk conditions and children 6 to 23 months
      old, respectively, whereas 41% gave high-priority to household contacts and
      caregivers of children <6 months old. Forty-three percent reported experiencing
      shortages of vaccine for patients at high risk, whereas only 14% ordered Chiron
      vaccine. In multivariate analyses, ordering vaccine from Chiron and ordering
      Aventis Pasteur (Lyon, France) vaccine solely from a vaccine distributor were
      associated with experiencing a shortage. Forty-eight percent of respondents
      obtained additional vaccine from another source, most frequently the public
      health sector, whereas 37% reported selling or giving away vaccine. In addition,
      47% referred patients at high risk elsewhere for vaccination, primarily to public
      health clinics. Forty-nine percent reported having unused vaccine remaining at
      the end of the season. CONCLUSIONS: Although few pediatricians ordered Chiron
      vaccine, substantial influenza vaccine shortages were reported, highlighting the
      tenuousness of injectable influenza vaccine supplies for children. The extensive
      redistribution of vaccine suggests that cooperative efforts between the private
      and public sectors were widespread. Efforts to vaccinate patients at high risk
      during shortages would be aided by better systems to identify and recall these
      patients.

PMID- 19171570
TI  - Diagnosis and management of acute sinusitis by pediatricians.
AB  - BACKGROUND: Acute sinusitis is frequently diagnosed in young children, yet little
      is known regarding pediatrician practices surrounding its diagnosis and
      management. OBJECTIVES: The purpose of this work was to describe how
      pediatricians diagnose and manage nonsevere acute sinusitis in otherwise healthy
      children < or =6 years of age. METHODS: We used a mail survey administered from
      June to August 2007 to a national random sample of 750 general pediatricians from
      the American Medical Association Master File. RESULTS. The response rate was 45%
      (N = 271). Pediatricians reported first considering acute sinusitis at the ages
      of 0 to 5 (6%), 6 to 11 (17%), 12 to 23 (36%), 24 to 35 (21%), and > or =36 (20%)
      months. Symptoms thought to be "very important" in the diagnosis of acute
      sinusitis included prolonged symptom duration (93%), purulent rhinorrhea (55%),
      and nasal congestion (43%); 60% reported that symptom duration is more important
      than symptom combination. Symptom durations expected before considering the
      diagnosis were 1 to 6 (3%), 7 to 9 (17%), 10 to 13 (37%), 14 to 16 (38%), and >
      or =17 (6%) days. Fifty-eight percent reported using sinus computed tomography
      scans "occasionally" or more often in the diagnosis of acute sinusitis. Ninety
      six percent reported treating acute sinusitis with an antibiotic "frequently" or
      "always." Fifty-three percent reported using contingency antibiotic prescriptions
      "occasionally" or more often for acute sinusitis. Adjuvants used "frequently" or
      "always" included saline washes (44%), systemic decongestants (28%), nasal
      corticosteroids (20%), and systemic antihistamines (13%). CONCLUSIONS: We found
      significant variation in the age at which pediatricians begin considering the
      diagnosis of nonsevere acute sinusitis in children. Most pediatricians consider
      symptom duration the most important diagnostic factor. The majority of
      pediatricians use sinus computed tomography imaging at least occasionally in
      young children with nonsevere symptoms despite its limitations in this clinical
      setting. Although poorly understood, the use of contingency antibiotic
      prescriptions is common. Lastly, the use of systemic decongestants and
      antihistamines in young children is reported, a practice that needs to be
      reexamined in light of recent Food and Drug Administration warnings regarding
      their safety.

PMID- 19171571
TI  - Who will speak for me? Improving end-of-life decision-making for adolescents with
      HIV and their families.
AB  - OBJECTIVES: The purpose of this research was to test the effectiveness of a model
      of family/adolescent-centered advance care planning for adolescents living with
      HIV and their families for increasing congruence and quality of communication
      while decreasing decisional conflict. PATIENTS AND METHODS: Ours was a 2-group,
      randomized, controlled trial in 2 hospital-based outpatient clinics in Washington
      and Memphis from 2006 to 2008. Participants (N = 38 dyads) included medically
      stable adolescents aged 14 to 21 years with HIV/AIDS and surrogates/families aged
      > or =21 years. Three 60- to 90-minute sessions were conducted 1 week apart via a
      semistructured family interview with a trained/certified interviewer. Each
      session encompassed, respectively: (1) Lyon Advance Care Planning Survey; (2)
      Respecting Choices interview; and (3) Five Wishes. Controls received (1)
      developmental history, (2) safety tips, and (3) future plans. Family congruence
      was measured by the Statement of Treatment Preferences and adolescent decisional
      conflict by the Decisional Conflict Scale, immediately after session 2.
      Communication was measured by the Quality of Participant-Interviewer
      Communication Scale after each session. RESULTS: Adolescent demographics were as
      follows: mean age was 16 years; 40% were boys; 92% were black; HIV transmission
      rate was 68% perinatal and 32% sexually acquired; 42% were asymptomatic; 29% were
      symptomatic; and 29% had a diagnosis of AIDS. Significantly increased congruence
      for testing the difference of the 2 kappa values for the 2 conditions was
      observed for intervention versus control dyads. Intervention adolescents reported
      feeling significantly better informed about end-of-life decisions. Intervention
      adolescents and all of the surrogates were more likely to feel that their
      attitudes and wishes were known by the interviewer over time. Intervention
      families, significantly more so than controls, rated the overall quality of
      discussion as very good to excellent. CONCLUSIONS: Family-centered advance care
      planning by trained facilitators increased congruence in adolescent/surrogate
      preferences for end-of-life care, decreased decisional conflict, and enhanced
      communication quality. Families acknowledged a life-threatening condition and
      were willing to initiate end-of-life conversations when their adolescents were
      medically stable.

PMID- 19171572
TI  - Neonatal palliative care attitude scale: development of an instrument to measure
      the barriers to and facilitators of palliative care in neonatal nursing.
AB  - OBJECTIVE: The aim of this research project was to obtain an understanding of the
      barriers to and facilitators of providing palliative care in neonatal nursing.
      This article reports the first phase of this research: to develop and administer
      an instrument to measure the attitudes of neonatal nurses to palliative care.
      METHODS: The instrument developed for this research (the Neonatal Palliative Care
      Attitude Scale) underwent face and content validity testing with an expert panel
      and was pilot tested to establish temporal stability. It was then administered to
      a population sample of 1285 neonatal nurses in Australian NICUs, with a response
      rate of 50% (N = 645). Exploratory factor-analysis techniques were conducted to
      identify scales and subscales of the instrument. RESULTS: Data-reduction
      techniques using principal components analysis were used. Using the criteria of
      eigenvalues being >1, the items in the Neonatal Palliative Care Attitude Scale
      extracted 6 factors, which accounted for 48.1% of the variance among the items.
      By further examining the questions within each factor and the Cronbach's alpha of
      items loading on each factor, factors were accepted or rejected. This resulted in
      acceptance of 3 factors indicating the barriers to and facilitators of palliative
      care practice. The constructs represented by these factors indicated barriers to
      and facilitators of palliative care practice relating to (1) the organization in
      which the nurse practices, (2) the available resources to support a palliative
      model of care, and (3) the technological imperatives and parental demands.
      CONCLUSIONS: The subscales identified by this analysis identified items that
      measured both barriers to and facilitators of palliative care practice in
      neonatal nursing. While establishing preliminary reliability of the instrument by
      using exploratory factor-analysis techniques, further testing of this instrument
      with different samples of neonatal nurses is necessary using a confirmatory
      factor-analysis approach.

PMID- 19171573
TI  - Usual source of care and unmet need among vulnerable children: 1998-2006.
AB  - OBJECTIVE: The purpose of this work was to identify the proportions of publicly
      (Medicaid and State Child Health Insurance Program) insured and uninsured
      children who did not identify a usual source of care from 1998 to 2006, spanning
      the State Children's Health Insurance Program (1997 to present) and the
      President's Health Center Initiative (2002 to present), and to characterize unmet
      medical need as it relates to insurance and a usual source of care for publicly
      insured and uninsured children. METHODS: We conducted a secondary data analysis
      of multiple years of the National Health Interview Survey. We identified the
      proportion of publicly insured and uninsured children aged 0 to 17 years who did
      not identify a usual source of care and stratified according to the site of care.
      We described the odds of reporting an unmet medical need according to insurance
      status and usual source of care, compared with privately insured children with a
      usual source of care. Sample weights were used to derive national estimates.
      RESULTS: From 1998 through 2006, there were significant increases in the
      proportions of children enrolled in Medicaid (16.7%-24.5%) and the State Child
      Health Insurance Program (2.0%-5.3%). The proportion of uninsured children has
      remained stable from 2002 to 2006 at approximately 10%. However, the proportion
      of uninsured reporting no usual source of care increased from 17.8% to 23.3%.
      Hispanic children had significant increases in the proportions of the uninsured
      and reporting no usual source of care by 2006. Hispanics constituted the largest
      proportion in both groups. Uninsured children and children without a usual source
      of care reported the highest odds of unmet need. Among the insured, publicly
      insured children had twice the odds of reporting an unmet need compared with
      privately insured children. CONCLUSIONS: During the State Child Health Insurance
      Program and the President's Health Center Initiative, growing proportions of
      uninsured children reported no usual source of care. Unmet medical need was the
      highest for the uninsured and those without a usual source of care. These
      findings suggest that initiatives designed to improve access to care must combine
      broadened insurance coverage with enhanced access to usual sources of care.

PMID- 19171574
TI  - Varicella vaccination and ischemic stroke in children: is there an association?
AB  - BACKGROUND: Ischemic stroke is a known complication of varicella disease.
      Although there have been case reports of ischemic stroke after varicella
      vaccination, the existence and magnitude of any vaccine-associated risk has not
      been determined. OBJECTIVE. The purpose of this work was to determine whether
      varicella vaccination is associated with an increased risk of ischemic stroke and
      encephalitis in children within 12 months after vaccination. PATIENTS AND
      METHODS: We conducted a retrospective cohort study based on computerized data
      from children 11 months through 17 years old enrolled for > or =12 months in the
      Vaccine Safety DataLink from 1991 through 2004. International Classification of
      Disease codes identified cases of ischemic stroke (433-436, 437.1, 437.4, 437.6,
      437.8-437.9) and encephalitis (052.0, 323.5, 323.8-9). Cox regression was used to
      model the risk in the 12 months after vaccination relative to all other person
      time. Covariates included calendar time, gender, and stroke risk factors (eg,
      sickle cell disease). RESULTS: Varicella vaccine was administered to 35.3% of the
      3.2 million children in the cohort. There were 203 new inpatient ischemic stroke
      diagnoses, including 8 that occurred within 12 months after vaccination; there
      was no temporal clustering. The adjusted stroke hazard ratio was not elevated
      during any of the time periods in the 12 months after vaccination. Stroke was
      strongly associated with known risk factors such as sickle cell disease and
      cardiac disease. None of the 243 encephalitis cases occurred during the first 30
      days after vaccination, and there was no association between encephalitis and
      varicella vaccination at any time in the 12 months after vaccination. CONCLUSION:
      Our retrospective cohort study of >3 million children found no association
      between varicella vaccine and ischemic stroke.

PMID- 19171575
TI  - Minitablets: new modality to deliver medicines to preschool-aged children.
AB  - OBJECTIVE: The goal was to assess the acceptability and suitability of placebo
      minitablets for preschool-aged children. METHODS: One hundred children 2 to 6
      years of age were recruited from a major London hospital. How to swallow the
      minitablet was discussed with the child, and chewing was discouraged. The parents
      were asked to administer 1 minitablet (placebo, 3-mm diameter) to the child. The
      outcomes were recorded as (1) swallowed, (2) chewed, (3) spat out, or (4) refused
      to take. RESULTS: Of the youngest children (2 years of age), almost one half
      (46%) swallowed the minitablet. The proportion increased to 53% for children 3
      years of age. Children > or =4 years of age were more likely to swallow the
      minitablet than not to swallow the minitablet, with 85% of 5-year-old children
      swallowing the minitablet. The ability to swallow the minitablet was not affected
      by gender. CONCLUSIONS: This study demonstrated the potential to use minitablets
      for the treatment of preschool-aged children and suggests that minitablets can be
      used as a potential new formulation for children in this age range.

PMID- 19171576
TI  - Skeletal surveys in infants with isolated skull fractures.
AB  - OBJECTIVE: The goal was to describe the utility of skeletal surveys and factors
      associated with both skeletal survey use and referral to child protective
      services for infants with skull fractures in the absence of significant
      intracranial injury. METHODS: A retrospective chart review was performed for
      infants who were evaluated at a tertiary children's hospital because of an
      isolated, non-motor vehicle-related, skull fracture between 1997 and 2006.
      Logistic regression analyses were used to test for associations of demographic
      factors, clinical findings that raised suspicion for abuse (absence of trauma
      history, changing history, delay in care, previous child protective services
      involvement, and other cutaneous injuries), and fracture type (simple versus
      complex) with the primary outcomes of skeletal survey use and reports to child
      protective services. RESULTS: Among the 341 infants in the study, 31% had
      clinical findings that raised suspicion for abuse and 42% had complex skull
      fractures. Skeletal surveys were obtained for 141 infants (41%) and detected
      additional fractures for only 2 (1.4%) of those 141 infants. Child protective
      services reports were made for 52 (15%) of the 341 children. Both infants with
      positive skeletal survey findings had other clinical findings that raised
      suspicion for abuse, and they were among those reported. With controlling for
      race and age, Medicaid-eligible/uninsured infants were more likely than privately
      insured infants to receive skeletal surveys and child protective services reports
      in the presence of a complex skull fracture or clinical findings that raised
      suspicion for abuse. CONCLUSION: Skeletal surveys were ordered frequently for
      infants with isolated skull fractures, but they rarely added additional
      information, beyond the history and physical findings, to support a report to
      child protective services.

PMID- 19171577
TI  - Health of children 3 to 17 years of age with Down syndrome in the 1997-2005
      national health interview survey.
AB  - OBJECTIVE: This study provides population-based estimates of recent medical
      conditions, concurrent developmental disorders, and health impact and utilization
      indicators for US children with and without Down syndrome. METHODS: The sample
      included children 3 to 17 years of age in the 1997-2005 National Health Interview
      Survey Child Sample Core and specifically included 146 children with Down
      syndrome, 604 children with mental retardation but without Down syndrome, and 95
      454 children without either condition reported. Developmental and medical
      conditions, health status, and service use were reported by parents or other
      knowledgeable caregivers. RESULTS: After adjustment for demographic factors,
      children with Down syndrome had higher odds, compared with children without
      mental retardation, of recent food/digestive allergy, frequent diarrhea/colitis,
      > or =3 ear infections in the previous year, very recent head/chest cold, and
      developmental disabilities other than mental retardation. They had increased odds
      that approached significance for recent seizures, very recent stomach/intestinal
      illness, and asthma. They had substantially higher rates (threefold or higher,
      compared with children without mental retardation) for nearly all health impact
      and health and special education service use measures. Of note, >25% of children
      with Down syndrome needed help with personal care, regularly took prescription
      medications, had recently seen a medical specialist, and received physical
      therapy or related therapy. The comparison group with mental retardation without
      Down syndrome represented many children with multiple serious disabilities who
      also had high rates of medical conditions and high levels of health impact and
      service use. CONCLUSION: These findings provide empirical, population-based data
      to inform guidelines for frequent monitoring and support for children with Down
      syndrome.

PMID- 19171578
TI  - Policies and characteristics of the preschool environment and physical activity
      of young children.
AB  - OBJECTIVE: The purpose of this study was to examine policies and characteristics
      of preschools and the extent to which they influence the physical activity of 3-
      to 5-year-old children during the preschool day. METHODS: A total of 299 children
      from 20 preschools wore accelerometers for an average of 8.1 hours/day (SD: 1.5
      hours/day), for 5.5 days (SD: 2.1 days). A researcher completed the Early
      Childhood Environment Rating Scale-Revised for each preschool to assess quality.
      Classrooms and playgrounds were measured, and the preschool director was
      interviewed about physical activity policies. For each policy or characteristic,
      preschools were divided into 2 groups on the basis of whether the
      characteristic/policy was presumed to promote or not promote physical activity.
      RESULTS: Children spent fewer minutes per hour in sedentary activity and more
      minutes per hour in moderate/vigorous physical activity in preschools that had
      higher quality scores, less fixed playground equipment, more portable playground
      equipment, lower use of electronic media, and larger playgrounds. Five preschools
      had all 5 of these characteristics, and children in those preschools had
      significantly more moderate/vigorous physical activity minutes per hour and fewer
      sedentary minutes per hour compared with children in the other preschools.
      CONCLUSION: Children in the top 5 physical activity-promoting preschools
      accumulated >60 minutes of moderate/vigorous physical activity per day, compared
      with the children in the other preschools, who accumulated <60 minutes of
      moderate/vigorous physical activity per day.

PMID- 19171579
TI  - Decreased aortic elasticity in healthy 11-year-old children exposed to tobacco
      smoke.
AB  - OBJECTIVE: The goal was to assess the relationship between passive smoking and
      arterial elasticity in children. METHODS: Healthy 11-year-old children (N = 386)
      from an atherosclerosis prevention trial (Special Turku Coronary Risk Factor
      Intervention Project for Children) were studied. Aortic and carotid elasticities
      were determined by using M-mode ultrasound imaging based on measurements of blood
      pressure and arterial diameter changes during the cardiac cycle. The aortic
      stiffness index, Young's elastic modulus, and distensibility and the respective
      indices for the carotid artery were calculated. Exposure to tobacco smoke was
      measured by using serum cotinine concentrations, and children were classified
      into 3 groups, that is, the noncotinine group (n = 220; undetectable cotinine
      levels), the low-cotinine group (n = 127; cotinine levels of 0.2-1.6 ng/mL), and
      the top-decile cotinine group (n = 39; cotinine levels of > or =1.7 ng/mL).
      RESULTS: Higher cotinine concentrations were associated with increased aortic
      stiffness index values. An increase in aortic Young's elastic modulus and a
      decrease in aortic distensibility were observed across the cotinine groups. In
      multivariate regression models, the cotinine level remained a significant
      explanatory variable regarding all aortic elasticity indices. Carotid elasticity
      indices showed no differences across the cotinine groups. CONCLUSIONS: Childhood
      exposure to tobacco smoke (verified with serum cotinine levels) decreases aortic
      elastic properties in healthy children.

PMID- 19171580
TI  - Parental smoking and adolescent smoking initiation: an intergenerational
      perspective on tobacco control.
AB  - OBJECTIVE: Adolescence is an important period of risk for the development of
      lifelong smoking behaviors. Compelling, although inconsistent, evidence suggests
      a relationship between parental smoking and the risk of smoking initiation during
      adolescence. This study investigates unresolved issues concerning the strength
      and nature of the association between parent smoking and offspring smoking
      initiation. METHODS: We enrolled 564 adolescents aged 12 to 17, along with 1 of
      their parents, into the New England Family Study between 2001 and 2004. Lifetime
      smoking histories were obtained from parents and their adolescent offspring.
      Discrete-time survival analysis was used to investigate the influence of parental
      smoking histories on the risk of adolescent smoking initiation. RESULTS: Parental
      smoking was associated with a significantly higher risk of smoking initiation in
      adolescent offspring. In addition, the likelihood of offspring smoking initiation
      increased with the number of smoking parents and the duration of exposure to
      parental smoking, suggesting a dose-response relationship between parental
      smoking and offspring smoking. Offspring of parents who had quit smoking were no
      more likely to smoke than offspring of parents who had never smoked. The effects
      of parental smoking on offspring initiation differed by sex (with a stronger
      effect of fathers' smoking on boys than girls), developmental period (with a
      stronger effect of parental smoking before the adolescent was age 13 than
      afterward), and residence of parents (with effects of fathers' smoking being
      dependent on living in the same household as the adolescent). Parental smoking
      was also associated with stronger negative reactions to adolescents' first
      cigarette, a potential marker of the risk of progression to higher levels of use.
      CONCLUSIONS: Parental smoking is an important source of vulnerability to smoking
      initiation among adolescents, and parental smoking cessation might attenuate this
      vulnerability.

PMID- 19171581
TI  - Water-pipe tobacco smoking among middle and high school students in Arizona.
AB  - BACKGROUND: Using a water pipe to smoke tobacco is increasing in prevalence among
      US college students, and it may also be common among younger adolescents. The
      purpose of this study of Arizona middle and high school students was to examine
      the prevalence of water-pipe tobacco smoking, compare water-pipe tobacco smoking
      with other forms of tobacco use, and determine associations between
      sociodemographic variables and water-pipe tobacco smoking in this population.
      METHODS: We added items assessing water-pipe tobacco smoking to Arizona's 2005
      Youth Tobacco Survey and used them to estimate statewide water-pipe tobacco
      smoking prevalence among various demographic groups by using survey weights. We
      also used multiple logistic regression to determine which demographic
      characteristics had independent relationships with each of 2 outcomes: ever use
      of water pipe to smoke tobacco and water-pipe tobacco smoking in the previous 30
      days. RESULTS: Median age of the sample was 14. Accounting for survey weights,
      among middle school students, 2.1% had ever smoked water-pipe tobacco and 1.4%
      had done so within the previous 30 days. Among those in high school, 10.3% had
      ever smoked from a water pipe and 5.4% had done so in the previous 30 days,
      making water-pipe tobacco smoking more common than use of smokeless tobacco,
      pipes, bidis, and kreteks (clove cigarettes). In multivariate analyses that
      controlled for covariates, ever smoking of water-pipe tobacco was associated with
      older age, Asian race, white race, charter school attendance, and lack of plans
      to attend college. CONCLUSIONS: Among Arizona youth, water pipe is the third most
      common source of tobacco after cigarettes and cigars. Increased national
      surveillance and additional research will be important for addressing this threat
      to public health.

PMID- 19171582
TI  - Binge pattern of alcohol consumption during pregnancy and childhood mental health
      outcomes: longitudinal population-based study.
AB  - OBJECTIVE: Patterns of alcohol consumption during pregnancy such as episodes of
      binge drinking may be as important as average levels of consumption in conferring
      risk for later childhood mental health and learning problems. However, it can be
      difficult to distinguish risk resulting from episodic or regular background
      levels of drinking. This large study investigates whether patterns of alcohol
      consumption are independently associated with child mental health and cognitive
      outcomes, whether there are gender differences in risk, and whether occasional
      episodes of higher levels of drinking carry any risk in the absence of regular
      daily drinking during pregnancy. METHODS: This prospective, population-based
      study used data from the Avon Longitudinal Study of Parents and Children. We
      investigated the relationships between a binge pattern of alcohol use
      (consumption of > or =4 drinks in a day) in the second and third trimesters of
      pregnancy and childhood mental health problems at 47 and 81 months of age (n =
      6355 and 5599, respectively). In a subgroup, we also investigated these
      relationships with child IQ at 49 months of age (n = 924). RESULTS: fter
      controlling for a range of prenatal and postnatal factors, any episodes of
      consuming > or =4 drinks in a day were independently associated with higher risks
      for mental health problems (especially hyperactivity/inattention) in girls at the
      age of 47 months and in both genders at 81 months. There was no association with
      IQ scores at 49 months after adjustment for confounders. The consumption of > or
      =4 drinks in a day continued to carry risk for mental health problems (especially
      hyperactivity/inattention) in the absence of regular daily drinking. CONCLUSIONS:
      The consumption of > or =4 drinks in a day on an occasional basis during
      pregnancy may increase risk for child mental health problems in the absence of
      moderate daily levels of drinking. The main risks seem to relate to hyperactivity
      and inattention problems.

PMID- 19171583
TI  - The cost of preterm birth throughout childhood in England and Wales.
AB  - BACKGROUND: Infants born preterm are at increased risk of adverse health and
      developmental outcomes. Mortality and morbidity after preterm birth impose a
      burden on finite public sector resources. This study considers the economic
      consequences of preterm birth from birth to adult life and compares the costs
      accruing to those born preterm with those born at term. METHODS: A decision
      analytic model was constructed to estimate the costs to the public sector over
      the first 18 years after birth, stratified by week of gestational age at birth.
      Costs were discounted and reported in UK pounds at 2006 prices. Probabilistic
      sensitivity analysis was used to examine uncertainty in the model parameters and
      generate confidence intervals surrounding the cost estimates. RESULTS: The model
      estimates the costs associated with a hypothetical cohort of 669601 children and
      is based on live birth and preterm birth data from England and Wales in 2006. The
      total cost of preterm birth to the public sector was estimated to be pound2.946
      billion (US $4.567 billion), and an inverse relationship was identified between
      gestational age at birth and the average public sector cost per surviving child.
      The incremental cost per preterm child surviving to 18 years compared with a term
      survivor was estimated at pound22885 (US $35471). The corresponding estimates for
      a very and extremely preterm child were substantially higher at pound61781 (US
      $95760) and pound94740 (US $146847), respectively. CONCLUSIONS: Despite concerns
      about ongoing costs after discharge from perinatal services, the largest
      contribution to the economic implications of preterm birth are hospital inpatient
      costs after birth, which are responsible for 92.0% of the incremental costs per
      preterm survivor.

PMID- 19171584
TI  - Reference ranges for hematocrit and blood hemoglobin concentration during the
      neonatal period: data from a multihospital health care system.
AB  - OBJECTIVE: "Reference ranges" are developed when it is impossible or
      inappropriate to establish "normal ranges" by drawing blood on healthy normal
      volunteers. Reference ranges for the hematocrit and the blood hemoglobin
      concentration of newborn infants have previously been reported from relatively
      small sample sizes by using measurement methods that now are considered outmoded.
      METHODS: We sought to develop reference ranges for hematocrit and hemoglobin
      during the neonatal period (28 days) by using very large sample sizes and modern
      hematology analyzers, accounting for gestational and postnatal age and gender.
      Data were assembled from a multihospital health care system after exclusion of
      patients with a high likelihood of an abnormal value and those who were receiving
      blood transfusions. RESULTS: During the interval from 22 to 40 weeks' gestation,
      the hematocrit and blood hemoglobin concentration increased approximately
      linearly. For every week advance in gestational age, the hematocrit increased by
      0.64% and the hemoglobin concentration increased by 0.21 g/dL. No difference was
      seen on the basis of gender. During the 4-hour interval after birth,
      hematocrit/hemoglobin values of late preterm and term neonates (35-42 weeks'
      gestation) increased by 3.6% +/- 0.5% (mean +/- SD), those of neonates of 29 to
      34 weeks' gestation remained unchanged, and those of <29 weeks' gestation
      decreased by 6.0% +/- 0.3%. During the first 28 days after birth, an
      approximately linear decrease in hematocrit/hemoglobin occurred. CONCLUSIONS: The
      figures presented herein describe reference ranges for hematocrit and blood
      hemoglobin concentration during the neonatal period, accounting for gestational
      and postnatal age.

PMID- 19171585
TI  - Clarification of laboratory and clinical variables that influence cystic fibrosis
      newborn screening with initial analysis of immunoreactive trypsinogen.
AB  - OBJECTIVES: To ensure that each newborn receives an equitable test of the highest
      possible sensitivity, we recognized the necessity to reassess immunoreactive
      trypsinogen and DNA issues in cystic fibrosis newborn screening algorithms. Our
      objectives included clarification of various factors that influence
      immunoreactive trypsinogen concentrations and resolution of long-standing
      questions about variations in immunoreactive trypsinogen levels among newborns.
      METHODS: Immunoreactive trypsinogen data on 660443 newborns who were born between
      July 1, 1994, and June 30, 2004, were abstracted from the Wisconsin State
      Laboratory of Hygiene databases and deidentified for analysis. Using a compiled
      data set, we analyzed various demographic characteristics to determine their
      role, if any, in immunoreactive trypsinogen variation. Specifically, season of
      birth, reagent lot, and birth weight were examined. Sensitivities of the most
      common cystic fibrosis newborn screening protocols, namely immunoreactive
      trypsinogen/immunoreactive trypsinogen and immunoreactive trypsinogen/DNA, were
      also investigated. RESULTS: Mean and 95th percentile immunoreactive trypsinogen
      levels were shown to vary by both season and reagent lot number and affect
      sensitivity of the assay. Low birth weight infants had significantly higher
      immunoreactive trypsinogen values than normal birth weight infants. Sensitivities
      were also found to vary on the basis of the algorithm used, with the highest
      sensitivity of 96.2% calculated for an immunoreactive trypsinogen/DNA protocol
      with 23 cystic fibrosis transmembrane conductance regulator mutation analyses
      compared with 80.2% with the immunoreactive trypsinogen/immunoreactive
      trypsinogen method used in 9 states. CONCLUSIONS: Floating, rather than fixed,
      cutoff values for the initial immunoreactive trypsinogen portion of any cystic
      fibrosis newborn screening protocol are generally necessary on the basis of the
      seasonal and reagent lot variations observed. Because of its lower sensitivity,
      immunoreactive trypsinogen/immunoreactive trypsinogen does not optimize detection
      of patients with cystic fibrosis.

PMID- 19171586
TI  - Twin zygosity studies and the genetic basis of neonatal morbidities.

PMID- 19171587
TI  - Dawn of the "bone phenotype" in cystic fibrosis.

PMID- 19171588
TI  - Sodium bicarbonate is beneficial in patients with diabetic ketoacidosis.

PMID- 19171589
TI  - Skin barrier therapy and neonatal mortality in preterm infants.

PMID- 19171590
TI  - Next steps in pulse oximetry screening research.

PMID- 19171591
TI  - Assessing the effects of computer-based documentation on parent-provider
      communication.

PMID- 19171592
TI  - Unexpected infant deaths associated with use of cough and cold medications.

PMID- 19171593
TI  - Trends in age at diagnosis and outcomes in biliary atresia.

PMID- 19171594
TI  - Systematic review of digital imaging screening strategies for retinopathy of
      prematurity.

PMID- 19171595
TI  - Routine newborn HIV testing: an idea whose time has come.

PMID- 19171596
TI  - Cold and cough medications in children: dealing with parental expectations.

PMID- 19171598
TI  - How are other first-world nations suppressing the adverse consequences of
      violence and youth sex in the modern media environment?

PMID- 19171599
TI  - Clinical prediction rules for meningitis in children pretreated with antibiotics.

PMID- 19171600
TI  - A question of volume?

PMID- 19171601
TI  - No association between hyperbilirubinemia and attention-deficit disorder.

PMID- 19171602
TI  - Antifungal prophylaxis: identification of preterm neonates at highest risk for
      invasive fungal infection.

PMID- 19171603
TI  - A review of the evidence for the medical home for children with special health
      care needs.

PMID- 19171604
TI  - Transition from pediatric to adult care: internists' perspectives.
AB  - OBJECTIVE: The goal was to understand the concerns of adult health care providers
      regarding transition for young adult patients with childhood-onset conditions.
      METHODS: Internists from the 2000 American Board of Medical Specialties directory
      were selected randomly. A 2-stage mail survey was conducted from August 2001 to
      November 2004. In stage 1, providers stated their concerns regarding accepting
      care of transitioning young adult patients. In stage 2, providers ranked their
      concerns. RESULTS: A total of 241 internal medicine providers were selected for
      participation. In stage 1, 134 of 241 physicians were eligible to participate,
      and 67 (50%) of 134 completed stage 1 surveys. In stage 2, 112 physicians were
      eligible, and 65 (58%) of 112 responded. Concerns elicited in stage 1 were
      clustered into 6 categories: patient maturity, patient psychosocial needs, family
      involvement, providers' medical competency, transition coordination, and health
      system issues. In stage 2, concerns rated highest were lack of training in
      congenital and childhood-onset conditions, lack of family involvement, difficulty
      meeting patients' psychosocial needs, needing a superspecialist, lack of
      adolescent training, facing disability/end-of-life issues during youth and early
      in the relationship, financial pressures limiting visit time, and families' high
      expectations. CONCLUSIONS: Internists clearly stated the need for better training
      in congenital and childhood-onset conditions, training of more adult
      subspecialists, and continued family involvement. They also identified concerns
      about patients' psychosocial issues and maturity, as well as financial support to
      care for patients with complex conditions.

PMID- 19171605
TI  - Effect of antibiotics for otitis media on mastoiditis in children: a
      retrospective cohort study using the United kingdom general practice research
      database.
AB  - BACKGROUND: Information is needed on whether mastoiditis has increased in
      association with the decline in antibiotics prescribed to children by primary
      care physicians in the United Kingdom. OBJECTIVE: To determine time trends in
      mastoiditis incidence, the frequency of antecedent otitis media, and the effect
      of antibiotics for otitis media on the risk of mastoiditis in children. PATIENTS
      AND METHODS: We conducted a retrospective cohort study by using the UK General
      Practice Research Database. Children aged 3 months to 15 years between 1990 and
      2006 were included. Risk of mastoiditis within 3 months after otitis media
      diagnosis and the protective effect of antibiotics were determined. RESULTS:
      There were 2 622 348 children within the General Practice Research Database; 854
      had mastoiditis, only one third of whom (35.7%) had antecedent otitis media.
      Mastoiditis incidence remained stable between 1990 and 2006 ( approximately 1.2
      per 10 000 child-years). Risk of mastoiditis, after otitis media, was 1.8 per 10
      000 episodes (139 of 792 623) after antibiotics compared with 3.8 per 10 000 (149
      of 389 649) without antibiotics, and increased with age. Antibiotics halved the
      risk of mastoiditis. General practitioners would need to treat 4831 otitis media
      episodes with antibiotics to prevent 1 child from developing mastoiditis. If
      antibiotics were no longer prescribed for otitis media, an extra 255 cases of
      childhood mastoiditis would occur, but there would be 738 775 fewer antibiotic
      prescriptions per year in the United Kingdom. CONCLUSIONS: Most children with
      mastoiditis have not seen their general practitioner for otitis media.
      Antibiotics halve the risk of mastoiditis, but the high number of episodes
      needing treatment to prevent 1 case precludes the treatment of otitis media as a
      strategy for preventing mastoiditis. Although mastoiditis is a serious disease,
      most children make an uncomplicated recovery after mastoidectomy or intravenous
      antibiotics. Treating these additional otitis media episodes could pose a larger
      public health problem in terms of antibiotic resistance.

PMID- 19171606
TI  - School recess and group classroom behavior.
AB  - OBJECTIVES: This study examines the amount of recess that children 8 to 9 years
      of age receive in the United States and compares the group classroom behavior of
      children receiving daily recess with that of children not receiving daily recess.
      METHODS: This is a secondary analysis of a public-use data set, the Early
      Childhood Longitudinal Study, Kindergarten Class of 1998-1999, third-grade data
      set. Children were categorized into 2 levels of recess exposure, that is,
      none/minimal break (<1 break of 15 minutes/day) or some recess. Some recess was
      further categorized into 5 levels on the basis of frequency and duration of
      recess. Child, parent, school, and classroom characteristics of those with and
      without recess were compared. The group classroom behavior was assessed by using
      the teacher's rating of class behavior. RESULTS: Complete data were available for
      10301 to 11624 children 8 to 9 years of age. There were equal numbers of boys and
      girls (boys: 50.3%). Children exposed to none/minimal break (30%) were much more
      likely to be black, to be from families with lower incomes and lower levels of
      education, to live in large cities, to be from the Northeast or South, and to
      attend public school, compared with those with recess. Teacher's rating of
      classroom behavior scores were better for children with some recess than for
      those with none/minimal break. This finding was maintained in multivariate
      regression analysis. However, among children receiving daily recess, the
      teacher's rating of class behavior scores did not differ significantly according
      to the level of exposure. CONCLUSIONS: These results indicated that, among 8- to
      9-year-old children, having > or =1 daily recess period of >15 minutes in length
      was associated with better teacher's rating of class behavior scores. This study
      suggests that schoolchildren in this age group should be provided with daily
      recess.

PMID- 19171607
TI  - Performance of a rapid antigen-detection test and throat culture in community
      pediatric offices: implications for management of pharyngitis.
AB  - OBJECTIVES: The goals were to establish performance characteristics of a rapid
      antigen-detection test and blood agar plate culture performed and interpreted in
      community pediatric offices and to assess the effect of the pretest likelihood of
      group A streptococcus pharyngitis on test performance (spectrum bias). METHODS:
      Two throat swabs were collected from 1848 children 3 to 18 years of age who were
      evaluated for acute pharyngitis between November 15, 2004, and May 15, 2005, in 6
      community pediatric offices. One swab was used to perform the rapid antigen
      detection test and a blood agar plate culture in the office and the other was
      sent to our laboratory for blood agar plate culture. Clinical findings were used
      to calculate the McIsaac score for each patient. The sensitivities of the office
      tests were calculated, with the hospital laboratory culture results as the
      criterion standard. RESULTS: Thirty percent of laboratory blood agar plate
      cultures yielded group A streptococcus (range among sites: 21%-36%). Rapid
      antigen-detection test sensitivity was 70% (range: 61%-80%). Office culture
      sensitivity was significantly greater, 81% (range: 71%-91%). Rapid antigen
      detection test specificity was 98% (range: 98%-99.5%), and office culture
      specificity was 97% (range: 94%-99%), a difference that was not statistically
      significant. The sensitivity of a combined approach using the rapid antigen
      detection test and back-up office culture was 85%. Among patients with McIsaac
      scores of >2, rapid antigen-detection test sensitivity was 78%, office culture
      sensitivity was 87%, and combined approach sensitivity was 91%. Positive
      diagnostic test results were significantly associated with McIsaac scores of >2.
      CONCLUSIONS: The sensitivity of the office culture was significantly greater than
      the sensitivity of the rapid antigen-detection test, but neither test was highly
      sensitive. The sensitivities of each diagnostic modality and the recommended
      combined approach were best among patients with greater pretest likelihood of
      group A streptococcus pharyngitis.

PMID- 19171608
TI  - Mortality rates for extremely low birth weight infants born in Japan in 2005.
AB  - OBJECTIVE: Our goal was to investigate the neonatal mortality rate and the
      mortality rate during the NICU stay for extremely low birth weight infants born
      in Japan in 2005. METHODS: The Committee of Neonatal Medicine of the Japan
      Pediatric Society retrospectively surveyed the deaths of extremely low birth
      weight infants born and hospitalized between January 1 and December 31, 2005.
      From 297 institutions in Japan, data on 3065 extremely low birth weight infants,
      which represented 98.4% of those reported in the maternal and health statistics
      of Japan in 2005, were collected. RESULTS: The neonatal mortality rate and the
      mortality rate during the NICU stay were 13.0% and 17.0%, respectively, which
      were lower than 17.7% and 21.5% in the survey in 2000. The neonatal mortality
      rates and the mortality rates during the NICU stay were 53.3% and 67.7% in the
      <400-g birth weight group (n = 62), 42.1% and 53.5% in the 400- to 499-g birth
      weight group (n = 159), 22.2% and 27.7% in the 500- to 599-g birth weight group
      (n = 387), 16.8% and 22.2% in the 600- to 699-g birth weight group (n = 537),
      9.4% and 12.7% in the 700- to 799-g birth weight group (n = 574), 6.3% and 9.1%
      in the 800- to 899-g birth weight group (n = 649), and 3.9% and 5.3% in the 900-
      to 999-g birth weight group (n = 697), respectively. The factors involved in the
      deaths of extremely low birth weight infants included lower gestational age,
      lower birth weight, male gender, multiple birth, institutions in which <10
      extremely low birth weight infants were admitted per year, and no prenatal
      maternal transfer. CONCLUSION: The mortality rates of extremely low birth weight
      infants who were born in 2005 demonstrated definite improvement.

PMID- 19171609
TI  - Economic evaluation of tandem mass spectrometry newborn screening in Australia.
AB  - OBJECTIVE: The goal was to investigate the cost-effectiveness of tandem mass
      spectrometry screening for the detection of inborn metabolic errors in an
      Australian setting. METHODS: Cost-effectiveness analysis from the health service
      perspective was undertaken on the basis of registry data for affected
      individuals. The intervention group was contrasted with both a contemporaneous
      group in nonscreening states and a historical cohort. The registry covers all
      individuals identified in Australia between 1994 and 2002. Main outcome measures
      were the total net cost of screening, the cost of treatment, life-years saved,
      and deaths averted. RESULTS: The total net cost of testing was estimated to be
      A$218 000 per 100 000 infants. Medical costs incurred by the intervention group
      exceeded those for the control group by A$131 000 per 100 000 infants. The number
      of life-years saved per 100 000 infants screened was 32.378 life-years per 100
      000 infants through an expected mortality rate reduction of 0.738 deaths per 100
      000 infants. The cost per death averted was estimated to be A$472 913 and the
      cost per life-year saved was estimated to be A$10 779, which compare favorably
      with existing cost-effectiveness standards. This conclusion is particularly
      robust because conservative assumptions were made throughout, because of data
      limitations. Sensitivity analyses suggested that this result was relatively
      robust to adjustment of model parameters. CONCLUSIONS: Tandem mass spectrometry
      screening for conditions caused by rare errors of metabolism is likely to be a
      cost-effective intervention in Australia.

PMID- 19171610
TI  - Spectrum and management of hypertriglyceridemia among children in clinical
      practice.
AB  - OBJECTIVES: The prevalence and identification of hypertriglyceridemia in youths
      will likely will increase in the future as a consequence of childhood obesity and
      increased screening for dyslipidemias. We sought to review our clinical
      experience with hypertriglyceridemia, evaluate factors associated with increased
      triglyceride levels, and review treatment options to provide guidance for
      management. METHODS: Clinical review of data for all patients who had > or =1
      elevated triglyceride level (>4 mmol/L [>350 mg/dL]) while being monitored in a
      specialized lipid disorders clinic was performed. RESULTS: The study population
      consisted of 76 patients with 761 clinic visits. Hypertriglyceridemia was
      secondary to lifestyle factors for 13 patients. The rest had primary
      hypertriglyceridemia, with 32 patients having familial combined
      hypertriglyceridemia and hypercholesterolemia (type II), 25 patients having
      primary hypertriglyceridemia (type IV), 4 patients having familial lipase
      deficiency (type I), and 2 patients having hyperlipoproteinemia E2/E2 phenotype
      (type III). Triglyceride levels were highest in type I and III
      hypertriglyceridemia (>10 mmol/L [>900 mg/dL]), followed by type IV and adiposity
      related hypertriglyceridemia (>4 mmol/L [>350 mg/dL]) and finally type II
      familial combined hypertriglyceridemia and hypercholesterolemia (>2 mmol/L [>180
      mg/dL]). A total of 34 patients received 37 trials of drug therapy as part of
      triglyceride level management (bile acid-binding resins, n = 12; fibrates, n =
      19; statins, n = 6). Triglyceride levels were found to decrease over time with
      the use of fibrates, to increase with the use of bile acid-binding resins, and
      not to change with the use of statins. CONCLUSIONS: Lifestyle modifications
      remain the primary therapeutic avenue for the management of pediatric
      hypertriglyceridemia. We propose an algorithm for the management of this
      heterogeneous population to guide clinicians in their treatment decisions.

PMID- 19171611
TI  - Increasing adherence to inhaled steroid therapy among schoolchildren: randomized,
      controlled trial of school-based supervised asthma therapy.
AB  - OBJECTIVE: We aimed to determine the effectiveness of school-based supervised
      asthma therapy in improving asthma control. The primary hypothesis was that the
      supervised-therapy group would have a smaller proportion of children experiencing
      an episode of poor asthma control each month, compared with those in the usual
      care group. METHODS: Children were eligible if they had physician-diagnosed
      persistent asthma, the need for daily controller medication, and the ability to
      use a dry-powder inhaler and a peak flowmeter. The trial used a 2-group,
      randomized, longitudinal design with a 15-month follow-up period. A total of 290
      children from 36 schools were assigned randomly to either school-based,
      supervised therapy or usual care. Ninety-one percent of the children were black,
      and 57% were male. The mean age was 11 years (SD: 2.1 years). An episode of poor
      asthma control was defined as > or =1 of the following each month: (1) an absence
      from school attributable to respiratory illness/asthma; (2) average use of rescue
      medication >2 times per week (not including preexercise treatment); or (3) > or
      =1 red or yellow peak flowmeter reading. RESULTS: Two hundred forty children
      completed the study. There were no differences in the likelihood of an episode of
      poor asthma control between the baseline period and the follow-up period for the
      usual-care group. For the supervised-therapy group, however, the odds of
      experiencing an episode of poor asthma control during the baseline period were
      1.57 times the odds of experiencing an episode of poor asthma control during the
      follow-up period. Generalized estimating equation modeling revealed a marginally
      significant intervention-time period interaction, indicating that children in the
      supervised-therapy group showed greater improvement in asthma control.
      CONCLUSIONS: Supervised asthma therapy improves asthma control. Clinicians who
      have pediatric patients with asthma with poor outcomes that may be attributable
      to nonadherence should consider supervised therapy.

PMID- 19171612
TI  - Neuropsychological performance 10 years after immunization in infancy with
      thimerosal-containing vaccines.
AB  - OBJECTIVE: Thimerosal, a mercury compound used as a preservative in vaccines
      administered during infancy, has been suspected to affect neuropsychological
      development. We compared the neuropsychological performance, 10 years after
      vaccination, of 2 groups of children exposed randomly to different amounts of
      thimerosal through immunization. METHODS: Children who were enrolled in an
      efficacy trial of pertussis vaccines in 1992-1993 were contacted in 2003. Two
      groups of children were identified, according to thimerosal content in vaccines
      assigned randomly in the first year of life (cumulative ethylmercury intake of
      62.5 or 137.5 microg), and were compared with respect to neuropsychological
      outcomes. Eleven standardized neuropsychological tests, for a total of 24
      outcomes, were administered to children during school hours. Mean scores of
      neuropsychological tests in the domains of memory and learning, attention,
      executive functions, visuospatial functions, language, and motor skills were
      compared according to thimerosal exposure and gender. Standard regression
      coefficients obtained through multivariate linear regression analyses were used
      as a measure of effect. RESULTS: Nearly 70% of the invited subjects participated
      in the neuropsychological assessment (N = 1403). Among the 24 neuropsychological
      outcomes that were evaluated, only 2 were significantly associated with
      thimerosal exposure. Girls with higher thimerosal intake had lower mean scores in
      the finger-tapping test with the dominant hand and in the Boston Naming Test.
      CONCLUSIONS: Given the large number of statistical comparisons performed, the few
      associations found between thimerosal exposure and neuropsychological development
      might be attributable to chance. The associations found, although statistically
      significant, were based on small differences in mean test scores, and their
      clinical relevance remains to be determined.

PMID- 19171613
TI  - Does breastfeeding protect against substantiated child abuse and neglect? A 15
      year cohort study.
AB  - OBJECTIVES: We explored whether breastfeeding was protective against maternally
      perpetrated child maltreatment. METHODS: A total of 7223 Australian mother-infant
      pairs were monitored prospectively over 15 years. In 6621 (91.7%) cases, the
      duration of breastfeeding was analyzed with respect to child maltreatment
      (including neglect, physical abuse, and emotional abuse), on the basis of
      substantiated child protection agency reports. Multinomial logistic regression
      was used to compare no maltreatment with nonmaternal and maternally perpetrated
      maltreatment and to adjust for confounding in 5890 cases with complete data
      (81.5%). Potential confounders included sociodemographic factors, pregnancy
      wantedness, substance abuse during pregnancy, postpartum employment, attitudes
      regarding infant caregiving, and symptoms of anxiety or depression. RESULTS: Of
      512 children with substantiated maltreatment reports, >60% experienced > or =1
      episode of maternally perpetrated abuse or neglect (4.3% of the cohort). The odds
      ratio for maternal maltreatment increased as breastfeeding duration decreased,
      with the odds of maternal maltreatment for nonbreastfed children being 4.8 times
      the odds for children breastfed for > or =4 months. After adjustment for
      confounding, the odds for nonbreastfed infants remained 2.6 times higher, with no
      association seen between breastfeeding and nonmaternal maltreatment. Maternal
      neglect was the only maltreatment subtype associated independently with
      breastfeeding duration. CONCLUSION: Among other factors, breastfeeding may help
      to protect against maternally perpetrated child maltreatment, particularly child
      neglect.

PMID- 19171614
TI  - Timing of delivery and survival rates for infants with prenatal diagnoses of
      congenital diaphragmatic hernia.
AB  - OBJECTIVES: The goal of the study was to test the hypothesis that infants with
      known congenital diaphragmatic hernias born at early term gestation (37-38 weeks)
      rather than later (39-41 weeks) had greater survival rates and less
      extracorporeal membrane oxygenation use. Primary outcomes were survival to
      hospital discharge or transfer and extracorporeal membrane oxygenation use.
      METHODS; A retrospective cohort study of term infants with prenatal diagnoses of
      congenital diaphragmatic hernia was performed with the Congenital Diaphragmatic
      Hernia Study Group Registry of patients with congenital diaphragmatic hernias who
      were treated between January 1995 and December 2006. RESULTS: Among 628 term
      infants at 37 to 41 weeks of gestation who had prenatal diagnoses of congenital
      diaphragmatic hernia and were free of major associated anomalies, early term
      birth (37 vs 39-41 weeks) and greater birth weight were associated independently
      with survival, whereas black race was related inversely to survival. Infants born
      at early term with birth weights at or above the group mean (3.1 kg) had the
      greatest survival rate (80%). Among infants born through elective cesarean
      delivery, infants born at 37 to 38 weeks of gestation, compared with 39 to 41
      weeks, had less use of extracorporeal membrane oxygenation (22.0% vs 35.5%) and a
      trend toward a greater survival rate (75.0% vs 65.8%). CONCLUSIONS: The timing of
      delivery is an independent, potentially important factor in the consideration of
      elective delivery for infants diagnosed prenatally as having congenital
      diaphragmatic hernias. Among fetuses with prenatally diagnosed congenital
      diaphragmatic hernias and without major associated anomalies, early term delivery
      may confer advantage.

PMID- 19171615
TI  - Longitudinal brain volume changes in preterm and term control subjects during
      late childhood and adolescence.
AB  - OBJECTIVE: Although preterm very low birth weight infants have a high prevalence
      of neuroanatomical abnormalities when evaluated at term-equivalent age, patterns
      of brain growth in prematurely born infants during school age and adolescence
      remain largely unknown. Our goal was to test the hypothesis that preterm birth
      results in long-term dynamic changes in the developing brain. METHODS: We
      performed serial volumetric MRI studies at ages 8 and 12 years in 55 preterm
      infants born weighing 600 to 1250 g and 20 term control children who participated
      in the follow-up component of a prospective, randomized, placebo-controlled
      intraventricular hemorrhage prevention study. RESULTS: Total brain volumes
      increased 2% to 3% between the ages of 8 and 12 years for both preterm and term
      children. These changes involved reductions in cerebral gray matter while white
      matter increased. Between 8 and 12 years of age, preterm subjects experienced a
      2% decrease in left cerebral gray matter compared with a 10% reduction in left
      cerebral gray for term controls. For right cerebral gray matter, preterm children
      experienced a 3% decrease in volume between years 8 and 12, compared with 9% for
      term controls (group-by-time). In contrast, preterm subjects had a 10% increase
      in cerebral white matter volumes bilaterally between ages 8 and 12 years,
      compared with >26% increases for both hemispheres for term controls. Significant
      differences in regional volume changes between study groups were found in
      bilateral temporal gray and in parietal white matter. CONCLUSIONS: Preterm birth
      continues to perturb the trajectory of cerebral development during late childhood
      and early adolescence with preterm children, showing both lower gray matter
      reduction and less white matter gain over time compared with term control
      subjects.

PMID- 19171616
TI  - Predicting motor development in very preterm infants at 12 months' corrected age:
      the role of qualitative magnetic resonance imaging and general movements
      assessments.
AB  - OBJECTIVE: The objective of this study was to compare the predictive value of
      qualitative MRI of brain structure at term and general movements assessments at 1
      and 3 months' corrected age for motor outcome at 1 year's corrected age in very
      preterm infants. PATIENTS AND METHODS: Eighty-six very preterm infants (<30
      weeks' gestation) underwent MRI at term-equivalent age, were evaluated for white
      matter abnormality, and had general movements assessed at 1 and 3 months'
      corrected age. Motor outcome at 1 year's corrected age was evaluated with the
      Alberta Infant Motor Scale, the Neuro-Sensory Motor Development Assessment, and
      the diagnosis of cerebral palsy by the child's pediatrician. RESULTS: At 1 year
      of age, the Alberta Infant Motor Scale categorized 30 (35%) infants as
      suspicious/abnormal; the Neuro-Sensory Motor Development Assessment categorized
      16 (18%) infants with mild-to-severe motor dysfunction, and 5 (6%) infants were
      classified with cerebral palsy. White matter abnormality at term and general
      movements at 1 and 3 months significantly correlated with Alberta Infant Motor
      Scale and Neuro-Sensory Motor Development Assessment scores at 1 year. White
      matter abnormality and general movements at 3 months were the only assessments
      that correlated with cerebral palsy. All assessments had 100% sensitivity in
      predicting cerebral palsy. White matter abnormality demonstrated the greatest
      accuracy in predicting combined motor outcomes, with excellent levels of
      specificity (>90%); however, the sensitivity was low. On the other hand, general
      movements assessments at 1 month had the highest sensitivity (>80%); however, the
      overall accuracy was relatively low. CONCLUSION: Neuroimaging (MRI) and
      functional (general movements) examinations have important complementary roles in
      predicting motor development of very preterm infants.

PMID- 19171617
TI  - Children with special health care needs: patterns of safety restraint use,
      seating position, and risk of injury in motor vehicle crashes.
AB  - OBJECTIVES: Special health care needs associated with behavioral conditions may
      influence a child's safety in motor vehicle crashes. The aim of this study was to
      describe and compare variation in restraint use, seating position, and injury
      risk in motor vehicle crashes among children with and without special health care
      needs likely to affect behavior. PATIENTS AND METHODS: This study uses data
      collected between December 1, 1998, and November 30, 2002, in a cross-sectional
      study of children <16 years of age who were involved in crashes of State Farm
      insured vehicles in 15 states. Parent reports via a validated telephone survey
      were used to define precrash special health care needs, restraint status, seating
      position, and the occurrence of clinically significant injuries by using a
      previously validated survey instrument. RESULTS: Complete data were collected for
      14654 children aged 4 to 15 years, representing 171633 children in crashes. Of
      these, 152 children were reported to have a special need likely to affect
      behavior, representing 1883 children. A greater proportion of children with
      special needs likely to affect behavior were appropriately restrained,
      particularly among children aged 4 to 8 years. Drivers of children with special
      needs likely to affect behavior were more often restrained and more often were
      the child passenger's parent. There were no differences in the rates of front-row
      seating. There was no significant association between the presence of a special
      need likely to affect behavior and risk of injury, after adjustment for
      child/driver characteristics and crash severity. CONCLUSIONS: Despite a greater
      proportion of children with special needs likely to affect behavior using proper
      vehicle restraint, their injury risk was similar to that of children without
      these special needs. Primary care pediatricians providing best practices for
      vehicle safety should consider the unique riding experience and risk of injury
      among children with special health care needs likely to affect behavior.

PMID- 19171618
TI  - Trends in hospitalizations for neonatal jaundice and kernicterus in the United
      States, 1988-2005.
AB  - CONTEXT AND OBJECTIVE: Recent reports have raised global concerns about a
      reemergence of kernicterus. Accurate information on the incidence of kernicterus
      is unavailable because of the rarity of the condition and the lack of a
      systematic surveillance strategy. We used nationally representative hospital
      discharge data to evaluate trends in the diagnosis and management of neonatal
      jaundice and the incidence of kernicterus in relation to the American Academy of
      Pediatrics hyperbilirubinemia clinical practice guideline. PATIENTS AND METHODS:
      The data came from the Healthcare Cost and Utilization Project family of
      databases. The Nationwide Inpatient Sample and the Kids' Inpatient Database were
      combined to generate trend data for the years 1988-2005. All neonatal discharges
      with primary or secondary International Classification of Diseases, Ninth
      Revision, Clinical Modification diagnoses codes for jaundice or kernicterus
      occurring within the first 30 days of life were selected with population
      incidence rates calculated from estimates of term and preterm newborn
      hospitalizations derived from the Healthcare Cost and Utilization Project data.
      To increase the reliability of identified kernicterus hospitalizations, newborns
      with a diagnosis of kernicterus and a procedure code for phototherapy or exchange
      transfusion were included as cases. RESULTS: Hospital diagnosis codes for
      kernicterus likely included a substantial number of rule-out cases, because
      approximately 70% did not include a procedure code for phototherapy or exchange
      transfusion. Including only cases with a procedure code for phototherapy or
      exchange transfusion resulted in 2.7 per 100000 diagnosed with kernicterus over
      the entire study period. A diagnosis code for jaundice was recorded for 15.6% of
      newborns. The diagnosis of jaundice and kernicterus differed according to race
      and gender. Rates also were elevated in preterm relative to term infants for both
      jaundice and kernicterus. Trends in diagnosis for newborn jaundice were u-shaped,
      with rates falling in the years before the initial American Academy of Pediatrics
      guideline (1988-1993) and increasing in the years after publication of the
      guideline (1997-2005). In contrast, the number of newborn hospitalizations with a
      diagnosis of kernicterus generally declined throughout the study period. Most of
      the decline in hospitalizations for term infants with a diagnosis of kernicterus
      occurred before and immediately after publication of the 1994 guideline, going
      from 5.1 per 100000 in 1988 to 1.5 per 100000 in the years from 1994 to 1996 and
      has since remained constant. CONCLUSIONS: Nationally representative hospital data
      indicate a declining incidence of hospitalizations with a diagnosis of
      kernicterus in newborn infants over the period 1988-2005. The decline occurred
      before and immediately after publication of the 1994 American Academy of
      Pediatrics guideline on hyperbilirubinemia. Epidemiologic findings were mostly
      consistent with other studies. Healthcare Cost and Utilization Project data
      provide an important system for monitoring hospitalizations of uncommon newborn
      conditions such as kernicterus.

PMID- 19171619
TI  - US infant mortality trends attributable to accidental suffocation and
      strangulation in bed from 1984 through 2004: are rates increasing?
AB  - OBJECTIVE: Accidental suffocation and strangulation in bed, a subgroup of sudden,
      unexpected infant deaths, is a leading mechanism of injury-related infant deaths.
      We explored trends and characteristics of these potentially preventable deaths.
      METHODS: In this descriptive study, we analyzed US infant mortality data from
      1984 through 2004. To explore trends in accidental suffocation and strangulation
      in bed and other sudden, unexpected infant deaths, we calculated cause-specific
      infant mortality rates and estimated proportionate mortality. Sudden, unexpected
      infant death was defined as a combination of all deaths attributed to accidental
      suffocation and strangulation in bed, sudden infant death syndrome, and unknown
      causes. Finally, we examined factors that were reported as contributing to these
      accidental suffocation and strangulation in bed deaths. RESULTS: Between 1984 and
      2004, infant mortality rates attributed to accidental suffocation and
      strangulation in bed increased from 2.8 to 12.5 deaths per 100000 live births.
      These rates remained relatively stagnant between 1984 and 1992 and increased
      between 1992 and 2004; the most dramatic increase occurred between 1996 and 2004
      (14% average annual increase). In contrast, total sudden, unexpected infant death
      rates remained stagnant between 1996 and 2004, whereas the proportion of deaths
      attributed to sudden infant death syndrome declined and to unknown cause
      increased. Black male infants <4 months of age were disproportionately affected
      by accidental suffocation and strangulation in bed. Beds, cribs, and couches were
      reported as places where deaths attributed to accidental suffocation and
      strangulation in bed occurred. CONCLUSIONS: Infant mortality rates attributable
      to accidental suffocation and strangulation in bed have quadrupled since 1984.
      The reason for this increase is unknown. Prevention efforts should target those
      at highest risk and focus on helping parents and caregivers provide safer sleep
      environments.

PMID- 19171620
TI  - Noise and light exposures for extremely low birth weight newborns during their
      stay in the neonatal intensive care unit.
AB  - OBJECTIVES: The objectives of this study were to characterize noise and light
      levels for extremely low birth weight newborns throughout their stay in the NICU,
      evaluate factors influencing noise and light levels, and determine whether
      exposures meet recommendations from the American Academy of Pediatrics. METHODS:
      Sound and light were measured inside the beds of extremely low birth weight
      newborns (n = 22) from birth to discharge. Measurements were recorded for 20
      consecutive hours weekly from birth until 36 weeks' postmenstrual age, biweekly
      until 40 weeks, and every 4 weeks thereafter. Clinical variables including bed
      type and method of respiratory support were recorded at each session. RESULTS:
      Age-related changes in respiratory support and bed type explained the weekly
      increase of 0.22 dB in sound level and 3.67 lux in light level. Old incubators
      were the noisiest bed types, and new incubators were the quietest. Light levels
      were significantly higher in open beds than in incubators. The variations in
      noise and light levels over time were greatest for open beds. Noise and light
      levels were much less affected by respiratory support in incubators compared with
      open beds. A typical extremely low birth weight neonate was exposed to noise
      levels averaging 56.44 dB(A) and light levels averaging 70.56 lux during their
      stay from 26 to 42 weeks' postmenstrual age in the NICU. Noise levels were rarely
      within American Academy of Pediatrics recommendations (5.51% of the time),
      whereas light levels almost always met recommendations (99.37% of the time).
      CONCLUSIONS: Bed type and respiratory support explained differences in noise and
      light levels that extremely low birth weight newborns experience during their
      hospital stay. Noise levels exceeded recommendations, although evidence
      supporting those recommendations is lacking. Well-designed intervention studies
      are needed to determine the effects of noise reduction on the development of
      extremely low birth weight newborns.

PMID- 19171621
TI  - Prenatal alcohol exposure and language delay in 2-year-old children: the
      importance of dose and timing on risk.
AB  - OBJECTIVE: The aim of this study was to investigate the association of dose and
      timing of prenatal alcohol exposure with early language acquisition. METHODS: We
      examined language delay in a randomly selected, population-based sample of
      Western Australian children born in 1995-1996 whose mothers had agreed to
      participate in a longitudinal study on health-related behaviors and who had
      completed the 2-year questionnaire (N = 1739). Information on alcohol consumption
      was collected at 3 months after birth for four periods; the three months pre
      pregnancy and for each trimester separately. Prenatal alcohol exposure was
      grouped into none, low, moderate-heavy and binge (>5) based on the total quantity
      consumed per week, quantity consumed per occasion, and frequency of consumption.
      The communication scale from the Ages & Stages Questionnaire was used to evaluate
      language delay. Logistic regression analysis was used to generate odds ratios and
      95% confidence intervals, adjusted for confounding factors. RESULTS: There was no
      association between low levels of alcohol consumption and language delay at any
      time period, although there was a nonsignificant 30% increase in risk when
      moderate-to-heavy levels of alcohol were consumed in the third trimester.
      Children exposed to a binge pattern of maternal alcohol consumption in the second
      trimester had nonsignificant, three-fold increased odds of language delay, with a
      similar estimate following third trimester alcohol exposure after controlling for
      covariates. CONCLUSIONS: This study did not detect an association between low
      levels of prenatal alcohol exposure and language delay when compared with women
      who abstained from alcohol during pregnancy. A nonsignificant threefold increase
      in the likelihood of language delay was seen in children whose mothers binged
      during late pregnancy. However, the small numbers of women with a binge-drinking
      pattern in late pregnancy limited the power of this study; studies analyzing
      larger numbers of children exposed to binge drinking in late pregnancy are
      needed.

PMID- 19171622
TI  - Parenting behavior is associated with the early neurobehavioral development of
      very preterm children.
AB  - OBJECTIVE: There is an increasing focus on social and environmental factors that
      promote and support the early development of highly vulnerable children such as
      those born very preterm. The aim of this study was to assess the relationship
      between parenting behavior, parent-child synchrony, and neurobehavioral
      development in very preterm children at 24 months of age. METHODS: Participants
      were 152 very preterm children (<30 weeks' gestation or <1250 g birth weight) and
      their parents/guardians. At 2 years' corrected age, parents/guardians and
      children completed a semistructured parent-child interaction task assessing dyad
      synchrony and parenting behavior (positive affect, negative affect, sensitivity,
      facilitation, and intrusiveness). Cognitive and motor development was assessed by
      using the Bayley Scales of Infant Development II, and the Infant Toddler Social
      and Emotional Assessment was used to assess socioemotional development (social
      emotional competence and internalizing and externalizing behavior). RESULTS: fter
      controlling for social risk, most parenting domains were associated with
      cognitive development, with parent-child synchrony emerging as the most
      predictive. Greater parent-child synchrony was also associated with greater
      social-emotional competence, as was parenting that was positive, warm, and
      sensitive. Parents who displayed higher levels of negative affect were more
      likely to rate their children as withdrawn, anxious, and inhibited, but,
      unexpectedly, higher negative affect was also associated with more optimal
      psychomotor development. Parenting was not associated with externalizing
      behaviors at this age. CONCLUSIONS: Specific parenting behaviors, particularly
      parent-child synchrony, were associated with neurobehavioral development. These
      findings have implications for the development of targeted parent-based
      interventions to promote positive outcomes across different developmental domains
      during the first 2 years of life for very preterm children.

PMID- 19171623
TI  - Evaluation of an intimate partner violence curriculum in a pediatric hospital.
AB  - OBJECTIVE: Intimate partner violence harms victims as well as families and
      communities. Many barriers account for limited intimate partner violence
      screening by nurses. The purpose of this study was to measure how participation
      in a curriculum about screening parents for intimate partner violence, at a
      pediatric hospital, affects a nurse's knowledge, attitudes, behaviors, and self
      efficacy for intimate partner violence screening. METHODS: In this
      interventional, longitudinal study, data were collected before participation in
      an intimate partner violence screening curriculum, after participation, and 3
      months later. The measurement tool was adapted from Maiuro's (2000) Self-efficacy
      for Screening for Intimate Partner Violence Questionnaire. RESULTS: Sixty-eight
      pediatric nurses completed all aspects of the study. At baseline, 18 (27%) nurses
      self-reported seeing a parent with an injury, and of those only 7 (39%) followed
      up with intimate partner violence screening. Factor analysis was performed on the
      baseline Self-efficacy for Screening for Intimate Partner Violence Questionnaire
      by using varimax rotation. Five factors were identified: conflict, fear of
      offending parent, self-confidence, appropriateness, and attitude. Only fear of
      offending parent was significantly different from times 1 to 3, indicating that
      nurses were less fearful after the training. Cronbach's alpha value for the total
      questionnaire at baseline was .85. Nurses reported significant improvement
      (baseline to 3-month follow-up) in several self-efficacy items. CONCLUSIONS:
      Participation in a 30-minute curriculum on intimate partner violence screening
      was associated with improvements in self-efficacy and significantly lower fear of
      offending parents 3 months after training. Nurses also showed improvement in the
      perception of resources available for nurses to manage intimate partner violence.
      Thirty-minute hospital-based curriculums that include victim testimonial video
      and practice role-playing to simulate parent interactions are recommended.

PMID- 19171624
TI  - Being bullied: associated factors in children and adolescents 8 to 18 years old
      in 11 European countries.
AB  - OBJECTIVES: To analyze the prevalence of bullying victims among children and
      adolescents aged 8 to 18 years in 11 European countries and to investigate the
      associated sociodemographic, physical, and psychosocial factors. METHODS: Being a
      bullying victim was measured by using the social acceptance (bullying) scale from
      the Kidscreen-52, a health-related quality-of-life questionnaire administered to
      16 210 children and adolescents aged 8 to 18 and their parents in postal or
      school-based surveys in 11 European countries. Standardized mean differences
      (effect size) were computed to measure the percentage of children/adolescents
      scoring 1 SD below the mean on the Kidscreen bullying scale. Logistic regression
      models were used to determine which sociodemographic, physical, and psychosocial
      factors were associated with being bullied. RESULTS: The percentage of children
      being bullied was 20.6% for the entire sample, ranging from 10.5% in Hungary to
      29.6% in the United Kingdom. In almost all countries the factors most strongly
      associated with being bullied were younger age, having probable mental health
      problems, having a low score on the Kidscreen-52 moods and emotions dimensions,
      and poor social support. Using the grand mean for all countries as the reference
      category, there was an above-average likelihood of children or adolescents
      reporting that they had been victims of bullying in 5 countries (Austria,
      Netherlands, Spain, Switzerland, and the United Kingdom), and a below-average
      likelihood in 3 countries (France, Greece, Hungary). CONCLUSIONS: This study
      indicated considerable variation between countries in the prevalence of those
      perceiving themselves to be victims of bullying but also revealed a clear profile
      of those likely to be bullied. The study also suggests that the Kidscreen
      bullying scale could be useful in identifying potential bullying victims.

PMID- 19171625
TI  - New opportunity to improve pediatric emergency preparedness: pediatric emergency
      assessment, recognition, and stabilization course.
AB  - The ideal first response to a life-threatening pediatric emergency includes early
      recognition of the emergency, activation of the appropriate emergency response
      system, performance of basic life support (cardiopulmonary
      resuscitation/automated external defibrillator treatment), and initiation of
      advanced life support, but the extent of resuscitation training among health care
      providers likely to be first at the side of a critically ill or injured child is
      often deficient. In the past, resuscitation courses beyond basic life support
      focused on training advanced providers. The Pediatric Emergency Assessment,
      Recognition, and Stabilization course was developed by the American Heart
      Association to target a broad range of health care providers who are likely to be
      first at the side of a child requiring resuscitation. It is hoped that training
      of health care providers through the Pediatric Emergency Assessment, Recognition,
      and Stabilization course will translate into early recognition of life
      threatening pediatric emergencies and greater resuscitation success, but results
      will depend on the availability of instruction and the maintenance of skills.

PMID- 19171626
TI  - Moral reflections on neonatal intensive care.

PMID- 19171627
TI  - The role of preschool home-visiting programs in improving children's
      developmental and health outcomes.
AB  - Child health and developmental outcomes depend to a large extent on the
      capabilities of families to provide a nurturing, safe environment for their
      infants and young children. Unfortunately, many families have insufficient
      knowledge about parenting skills and an inadequate support system of friends,
      extended family, or professionals to help with or advise them regarding child
      rearing. Home-visiting programs offer a mechanism for ensuring that at-risk
      families have social support, linkage with public and private community services,
      and ongoing health, developmental, and safety education. When these services are
      part of a system of high-quality well-child care linked or integrated with the
      pediatric medical home, they have the potential to mitigate health and
      developmental outcome disparities. This statement reviews the history of home
      visiting in the United States and reaffirms the support of the American Academy
      of Pediatrics for home-based parenting education and support.

PMID- 19171628
TI  - Clinical inactivity among pediatricians: prevalence and perspectives.
AB  - INTRODUCTION: During their careers, physicians may have periods of clinical
      inactivity for a variety of reasons. Concerns have been raised about the impact
      of clinical inactivity on the growing physician workforce shortage. It is unknown
      how these periods of clinical inactivity impact physician competence and patient
      safety. With this study we sought to determine the rates of clinical inactivity,
      the duration of periods of inactivity, professional activities during those
      periods, and the perspective of pediatricians regarding future requirements of
      competency for return to clinical practice. PATIENTS AND METHODS: A random sample
      of 6757 American Board of Pediatrics diplomates aged < or =65 years received a
      structured questionnaire by mail. The survey explored the prevalence of and
      reasons for clinical inactivity and perspectives on the return to clinical
      practice. Clinical inactivity was defined as a period of absence of > or =12
      months from any direct or consultative clinical care. RESULTS: The response rate
      was 74%. Of respondents, 88% (n = 4176) were currently engaged in pediatric
      clinical care. Twelve percent (n = 554) indicated that they had experienced a
      period of clinical inactivity lasting > or =12 months. Women were more likely
      than men (16% vs 7%) to have had periods of clinical inactivity. Controlling for
      gender, generalists were no more likely than subspecialists to report a past
      period of clinical inactivity. More than one third of the respondents (n = 1672
      [36%]) agreed that pediatricians who return from clinical inactivity after >1
      year should undergo a competency evaluation. CONCLUSIONS: Almost 1 in 8
      pediatricians has suspended clinical care for > or =1 year, and a similar
      proportion of respondents were inactive at the time of our survey. Currently, all
      of these physicians may maintain both their licensure and board certification
      during these periods. The impact of clinical inactivity on patient care and
      patient safety is unknown.

PMID- 19171629
TI  - Hallucinations and other psychotic symptoms associated with the use of attention
      deficit/hyperactivity disorder drugs in children.
AB  - OBJECTIVES: To gain a better understanding of the capacity of psychostimulant
      medications to induce adverse psychiatric reactions and determine the frequency
      of such reactions, we analyzed postmarketing surveillance data and clinical trial
      data for drugs, either approved or under development, for the treatment of
      attention-deficit/hyperactivity disorder. METHODS: The US Food and Drug
      Administration requested manufacturers of drugs approved for attention
      deficit/hyperactivity disorder or with active clinical development programs for
      that indication to search their electronic clinical trial databases for cases of
      psychosis or mania using prespecified search terms. The manufacturers supplied
      descriptions of clinical trials, numbers of patients exposed to study drug, and
      duration of exposure to permit calculations of incidence rates. Independently,
      cases of psychosis or mania in children and adults for drugs used to treat
      attention-deficit/hyperactivity disorder from the Food and Drug Administration
      Adverse Event Reporting System safety database were analyzed. Manufacturers were
      asked to conduct similar analyses of their postmarketing surveillance databases.
      RESULTS: We analyzed data from 49 randomized, controlled clinical trials in the
      pediatric development programs for these products. A total of 11 psychosis/mania
      adverse events occurred during 743 person-years of double-blind treatment with
      these drugs, and no comparable adverse events occurred in a total of 420 person
      years of placebo exposure in the same trials. The rate per 100 person-years in
      the pooled active drug group was 1.48. The analysis of spontaneous postmarketing
      reports yielded >800 reports of adverse events related to psychosis or mania. In
      approximately 90% of the cases, there was no reported history of a similar
      psychiatric condition. Hallucinations involving visual and/or tactile sensations
      of insects, snakes, or worms were common in cases in children. CONCLUSIONS:
      Patients and physicians should be aware that psychosis or mania arising during
      drug treatment of attention-deficit/hyperactivity disorder may represent adverse
      drug reactions.

PMID- 19171630
TI  - Brain and ventricles in very low birth weight infants at term: a comparison among
      head circumference, ultrasound, and magnetic resonance imaging.
AB  - OBJECTIVES: The aim of this study was to assess the relationship among the size
      of the lateral ventricles, head-circumference measure, and brain volumes. In
      addition, the association between ventricular dilatation and various brain
      lesions was defined. PATIENTS AND METHODS: A total of 257 preterm very low birth
      weight (< or =1500 g) infants who met the inclusion criteria were born in Turku
      University Central Hospital between 2001 and 2006. A total of 209 (84.8%) of 218
      survivors participated in the study. The measurements at term included the
      ventricular brain ratio, the widths of the frontal and occipital horns of the
      lateral ventricles by ultrasound, total and regional brain volumes by MRI, and
      head circumference. Brain lesions were defined by ultrasound at 3 to 5, 7 to 10,
      and 30 days of age monthly until discharge and by MRI and ultrasound at term.
      RESULTS: An abnormal ventricular brain ratio (>0.35), an increasing number of
      dilated ventricular horns, and smaller head circumference were significantly
      associated with smaller total brain tissue volume. The abnormal ventricular brain
      ratio and the increasing number of dilated ventricular horns in ultrasound
      associated with larger ventricular volumes in MRI, and a smaller head
      circumference was associated significantly with reduced regional brain tissue
      volumes. Brain lesions were more common in infants with ventriculomegaly.
      CONCLUSIONS: The ventricular brain ratio, widths of the lateral ventricular
      horns, and head circumference are appropriate measures for the estimation of both
      total and regional brain tissue volumes. Ventriculomegaly is strongly associated
      with brain lesions.

PMID- 19171631
TI  - Folate, related B vitamins, and homocysteine in childhood and adolescence:
      potential implications for disease risk in later life.
AB  - OBJECTIVES: Folate and the metabolically related B vitamins are an important
      priority throughout life, but few studies have examined their status through
      childhood and adolescence. The aims of the current study were to investigate age,
      gender, and lifestyle factors as determinants of folate, related B-vitamin
      status, and homocysteine concentrations among British children and adolescents
      and to propose age-specific reference ranges for these biomarkers, which, at
      present, are unavailable. PARTICIPANTS AND METHODS: Data from the National
      Dietary and Nutritional Survey of 2127 young people aged 4 to 18 years were
      accessed to provide a representative sample of British children. All of the
      subjects who provided a blood sample for homocysteine concentrations were
      included in the current study (n = 840). Of these, laboratory biomarkers of
      folate (serum and red cell folate: n = 832 and 774, respectively), vitamin B(12)
      (n = 828), vitamin B(6) (n = 770), and riboflavin (n = 839) were also examined.
      RESULTS: The biomarker status of all 4 of the relevant B vitamins decreased
      significantly with age. Correspondingly, homocysteine concentrations
      progressively increased, with median values of 5.6, 6.3, and 7.9 mumol/L for
      children aged 4 to 10 years, 11 to 14 years, and 15 to 18 years, respectively,
      and were higher in boys compared with girls (15-18 years only). Independent of
      age and gender, fortified breakfast cereal intake (consumed by 89% of the sample)
      was associated with significantly higher B-vitamin status and lower homocysteine
      concentrations. CONCLUSIONS: It is not generally appreciated that the well
      established progressive increase in homocysteine from 4 to 18 years reflects
      decreases in the biomarker status of all 4 metabolically related B vitamins. We
      suggest age-specific laboratory reference ranges for homocysteine and related B
      vitamin concentrations for potential use within a pediatric setting.

PMID- 19171633
TI  - Protecting the public: state medical board licensure policies for active and
      inactive physicians.
AB  - OBJECTIVE: The purpose of this research was to explore state physician licensing
      board policies and regulation of active, inactive, and retired licenses. METHODS:
      We conducted structured telephone interviews from January to March 2007 with
      representatives of all 64 state allopathic and osteopathic medical licensing
      boards in the United States. All of the licensing boards participated. RESULTS:
      Only 34% of state licensing boards query physicians regarding clinical activity
      at both initial licensure and renewal. The majority of boards allow physicians to
      hold or renew an unrestricted active license to practice medicine, although they
      may not have cared for a patient in years. Only 1 board requires a minimum number
      of patient visits to maintain an active license. Five boards allow physicians
      with inactive licenses to practice some form of medicine, whereas 7 boards allow
      physicians with retired licenses to practice. Few states have any mechanism to
      assess the competency of clinically inactive physicians who return to active
      practice. CONCLUSIONS: The number of inactive physicians in the United States is
      growing. Currently, state medical board policies do not address the issue of
      continuing competence in license renewal. Greater medical safety concerns on the
      part of the public will likely lead to calls for greater accountability by state
      licensing authorities.

PMID- 19171632
TI  - Prolonged intravenous therapy versus early transition to oral antimicrobial
      therapy for acute osteomyelitis in children.
AB  - OBJECTIVES: Early transition from intravenous to oral antimicrobial therapy for
      acute osteomyelitis in children has been suggested as a safe and effective
      alternative to traditional prolonged intravenous therapy via central venous
      catheter, but no studies have directly compared these 2 treatment modalities. We
      sought to compare the effectiveness of early transition from intravenous to oral
      antimicrobial therapy versus prolonged intravenous antimicrobial therapy for the
      treatment of children with acute osteomyelitis. METHODS: We conducted a
      retrospective cohort study of children aged 2 months to 17 years diagnosed with
      acute osteomyelitis between 2000 and 2005 at 29 freestanding children's hospitals
      in the United States to confirm the extent of variation in the use of early
      transition to oral therapy. We used propensity scores to adjust for potential
      differences between children treated with prolonged intravenous therapy and
      logistic regression to model the association of outcome (treatment failure rates
      within 6 months of diagnosis) and difference in the mode of therapy within
      hospitals and across hospitals. RESULTS: Of the 1969 children who met inclusion
      criteria, 1021 received prolonged intravenous therapy and 948 received oral
      therapy. The use of prolonged intravenous therapy varied significantly across
      hospitals (10%-95%). The treatment failure rate was 5% (54 of 1021) in the
      prolonged intravenous therapy group and 4% (38 of 948) in the oral therapy group.
      There was no significant association between treatment failure and the mode of
      antimicrobial therapy. Thirty-five (3.4%) children in the prolonged intravenous
      therapy group were readmitted for a catheter-associated complication.
      CONCLUSIONS: Treatment of acute osteomyelitis with early transition to oral
      therapy is not associated with a higher risk of treatment failures and avoids the
      risks of prolonged intravenous therapy through central venous catheters.

PMID- 19171634
TI  - Persistence of morbidity and cost differences between late-preterm and term
      infants during the first year of life.
AB  - BACKGROUND: Late-preterm infants are known to have greater morbidity and costs
      compared with term infants during the neonatal period, but less is known about
      whether these differences continue beyond this period. OBJECTIVE: The purpose of
      this study was to examine the most common causes and costs of rehospitalization
      and other health care use among late-preterm and term infants throughout the
      first year of life. METHODS: We conducted a retrospective cohort study of late
      preterm (33-36 weeks' gestation) and term infants born in 2004 with > or =1 year
      of enrollment in a large national US database of commercially insured members.
      All of the reported health care services and costs were examined from the birth
      hospitalization through the first year of life. RESULTS: We evaluated 1683 late
      preterm and 33 745 term infants. The average length of stay of the birth
      hospitalization for term infants was 2.2 days, and the average cost was $2061.
      Late-preterm infants had a substantially longer average stay of 8.8 days and
      average cost of $26 054. Total first-year costs after birth discharge were, on
      average, 3 times as high among late-preterm infants ($12 247) compared with term
      infants ($4069). Late-preterm infants were rehospitalized more often than term
      infants (15.2% vs 7.9%). A subset of late-preterm infants that were discharged
      late from their birth hospitalization had the highest rates of rehospitalization
      and total health care costs. Higher costs during rehospitalization of late
      preterm infants, especially those with a late discharge, indicate their
      propensity to have more severe illness. CONCLUSIONS: Late-preterm infants have
      greater morbidity and total health care costs than term infants, and these
      differences persist throughout the first year of life. Management strategies and
      guidelines to reduce morbidity and costs in late-preterm infants should be
      investigated.

PMID- 19171635
TI  - Routine developmental screening implemented in urban primary care settings: more
      evidence of feasibility and effectiveness.
AB  - OBJECTIVES: The purpose of this study was to examine the feasibility and
      effectiveness of implementation of validated developmental screening by using the
      Parents' Evaluation of Developmental Status in 2 urban pediatric practices.
      DESIGN AND METHODS: We implemented the Parents' Evaluation of Developmental
      Status at Boston Children's Hospital Primary Care Center and at Joseph Smith
      Community Health Center as quality improvement initiatives. Each practice offered
      screening to all of the patients attending well-child care visits between 6
      months and 8 years of age. The implementation process was investigated by using
      preimplementation and postimplementation surveys and a focus group of pediatric
      primary care providers. To assess outcomes, such as changes in identification
      rates and referrals for developmental and behavioral concerns, we reviewed
      medical charts of all of the 2- and 3-year-olds present at Children's Hospital
      Primary Care Center well-child care visits in the periods before and after
      screening implementation. RESULTS: Providers found routine screening easier than
      expected and feasible to conduct in a busy primary care setting. The practice
      change resulted in screening of 61.6% of eligible children. Compared with same
      aged children before screening, after screening was implemented more behavioral
      concerns were detected in the 2-year-old group, and more children with
      developmental concerns were identified in the 3-year-old group. Referral rates
      for additional evaluation increased only for 3-year-olds, although the types of
      referrals (ie, audiology and early intervention) were consistent as those found
      before screening started. CONCLUSIONS: Implementation of validated screening by
      using the Parents' Evaluation of Developmental Status was feasible in large,
      urban settings. Effectiveness was demonstrated via chart review documenting an
      increased rate of identification of developmental and behavioral concerns.
      Perceived obstacles, such as the time requirement, should not prevent widespread
      adoption of screening.

PMID- 19171636
TI  - Genetic contribution to patent ductus arteriosus in the premature newborn.
AB  - BACKGROUND: The most common congenital heart disease in the newborn population,
      patent ductus arteriosus, accounts for significant morbidity in preterm newborns.
      In addition to prematurity and environmental factors, we hypothesized that
      genetic factors play a significant role in this condition. OBJECTIVE: The
      objective of this study was to quantify the contribution of genetic factors to
      the variance in liability for patent ductus arteriosus in premature newborns.
      PATIENTS AND METHODS: A retrospective study (1991-2006) from 2 centers was
      performed by using zygosity data from premature twins born at < or =36 weeks'
      gestational age and surviving beyond 36 weeks' postmenstrual age. Patent ductus
      arteriosus was diagnosed by echocardiography at each center. Mixed-effects
      logistic regression was used to assess the effect of specific covariates. Latent
      variable probit modeling was then performed to estimate the heritability of
      patent ductus arteriosus, and mixed-effects probit modeling was used to quantify
      the genetic component. RESULTS: We obtained data from 333 dizygotic twin pairs
      and 99 monozygotic twin pairs from 2 centers (Yale University and University of
      Connecticut). Data on chorioamnionitis, antenatal steroids, gestational age, body
      weight, gender, respiratory distress syndrome, patent ductus arteriosus,
      necrotizing enterocolitis, oxygen supplementation, and bronchopulmonary dysplasia
      were comparable between monozygotic and dizygotic twins. We found that
      gestational age, respiratory distress syndrome, and institution were significant
      covariates for patent ductus arteriosus. After controlling for specific
      covariates, genetic factors or the shared environment accounted for 76.1% of the
      variance in liability for patent ductus arteriosus. CONCLUSIONS: Preterm patent
      ductus arteriosus is highly familial (contributed to by genetic and environmental
      factors), with the effect being mainly environmental, after controlling for known
      confounders.

PMID- 19171637
TI  - Patent ductus arteriosus therapy: impact on neonatal and 18-month outcome.
AB  - OBJECTIVE: The purpose of this work was to evaluate therapy for patent ductus
      arteriosus as a risk factor for death or neurodevelopmental impairment at 18 to
      22 months, bronchopulmonary dysplasia, or necrotizing enterocolitis in extremely
      low birth weight infants. METHODS: We studied infants in the National Institute
      of Child Health and Human Development Neonatal Research Network Generic Data Base
      born between 2000 and 2004 at 23 to 28 weeks' gestation and at <1000-g birth
      weight with patent ductus arteriosus. Patent ductus arteriosus therapy was
      evaluated as a risk factor for outcomes in bivariable and multivariable analyses.
      RESULTS: Treatment for subjects with patent ductus arteriosus (n = 2838) included
      403 receiving supportive treatment only, 1525 treated with indomethacin only, 775
      with indomethacin followed by secondary surgical closure, and 135 treated with
      primary surgery. Patients who received supportive therapy for patent ductus
      arteriosus did not differ from subjects treated with indomethacin only for any of
      the outcomes of interest. Compared with indomethacin treatment only, patients
      undergoing primary or secondary surgery were smaller and more premature. When
      compared with indomethacin alone, primary surgery was associated with increased
      adjusted odds for neurodevelopmental impairment and bronchopulmonary dysplasia in
      multivariable logistic regression. Secondary surgical closure was associated with
      increased odds for neurodevelopmental impairment and increased adjusted odds for
      bronchopulmonary dysplasia but decreased adjusted odds for death. Risk of
      necrotizing enterocolitis did not differ among treatments. Indomethacin
      prophylaxis did not significantly modify these results. CONCLUSIONS: Our results
      suggest that infants treated with primary or secondary surgery for patent ductus
      arteriosus may be at increased risk for poor short- and long-term outcomes
      compared with those treated with indomethacin. Prophylaxis with indomethacin in
      the first 24 hours of life did not modify the subsequent outcomes of patent
      ductus arteriosus therapy.

PMID- 19171638
TI  - Cord blood leptin and adiponectin as predictors of adiposity in children at 3
      years of age: a prospective cohort study.
AB  - OBJECTIVES: Leptin and adiponectin are adipocyte-secreted hormones that regulate
      energy homeostasis and metabolism. Because their roles in the neonatal period and
      in early childhood are poorly understood, we aimed in this prospective cohort
      study to determine the extent to which umbilical cord blood leptin and
      adiponectin concentrations predict measures of adiposity and growth at 3 years of
      age. PATIENTS AND METHODS: We studied 588 children participating in the
      prospective prebirth cohort study Project Viva. We examined associations of cord
      blood leptin and adiponectin levels with weight changes during the first 6 months
      of life, 3-year circulating leptin and adiponectin concentrations, and the
      following adiposity-related outcomes at 3 years of age: BMI z score, height-for
      age z score, and sums of triceps and subscapular skinfold thicknesses to
      represent overall adiposity, as well as subscapular/triceps skinfold ratio to
      represent central adiposity. RESULTS: Cord blood leptin and adiponectin were each
      directly associated with the duration of gestation and birth weight for
      gestational age z scores. Cord blood leptin levels were negatively associated
      with change in weight-for-length, weight-for-age, and length-for-age z scores
      between birth and 6 months of age. Similarly, cord blood adiponectin was
      negatively associated with change in weight-for-length and weight-for-age z
      scores. After adjusting for several maternal and child factors related to
      obesity, each 10 ng/mL increment of cord blood leptin was associated with a
      reduction in BMI z score and higher leptin levels at 3 years but not with
      skinfold thicknesses. Each 10 microg/mL increment of cord blood adiponectin was
      positively associated with a higher subscapular skinfold thickness/triceps
      skinfold thickness ratio at 3 years. CONCLUSIONS: Lower cord blood leptin levels
      are associated with smaller size at birth but more pronounced weight gain in the
      first 6 months of life and higher BMI at 3 years of age. Cord blood adiponectin
      levels are also directly associated with birth weight for gestational age,
      inversely associated with weight gain in the first 6 months of life, and predict
      an increase in central adiposity at age 3 years.

PMID- 19171639
TI  - Sports injuries to high school athletes with disabilities.
AB  - INTRODUCTION: Physical activity in sports comes with an inherent risk for injury.
      For children with disabilities, their injury risk may be complicated by
      preexisting disability. However, very little research exists on sports injuries
      to young athletes with disabilities. To best manage potential injuries to
      children with disabilities, data on sports injury patterns are needed. The
      purpose of this study was to measure the frequency of and risk factors for injury
      to high school athletes with disabilities. METHODS: A total of 210 athletes from
      8 special education high schools that are part of an interscholastic sports
      league participated in the study. Seven of the 8 schools were followed for 1
      season each of basketball, softball, soccer, and field hockey, and 1 school
      enrolled only during field hockey. Data were collected from coaches on daily
      exposure sessions (game, practice, and conditioning, as well as length of
      session), athlete characteristics (disability, gender, age, seizure history, and
      behavioral problems), and nature of injuries resulting in any type of medical
      treatment. RESULTS: Thirty-eight injuries were reported among 512 special
      athletes for a rate of 2.0 per 1000 athlete exposures. Soccer (3.7 per 1000) had
      the highest rate of injury. More than half of the injuries were abrasions and
      contusions. Those at highest risk for injury were athletes with autism, athletes
      with histories of seizures, and starters. Athletes with autism had approximately
      5 times the injury rate of athletes with mental disabilities. Athletes with
      seizures had >2.5 times the rate of injury reported among those with no seizure
      history. CONCLUSIONS: This adapted sports program is a reasonably safe activity
      for children with disabilities. Nonetheless, findings have important implications
      for prevention. The preparticipation medical examination may be an excellent
      opportunity to create special guidelines, particularly for athletes with autism
      and seizure history.

PMID- 19171640
TI  - Mental health problems and overweight in a nationally representative sample of
      adolescents: effects of race and ethnicity.
AB  - OBJECTIVES: In this study we examined the relation between mental health problems
      and weight in a population-based study of youth aged 12 to 17 years and whether
      the association between mental health problems and weight is moderated by race
      and ethnicity. METHODS: We used 2003 National Survey on Children's Health data.
      Logistic regression was used to arrive at adjusted odds ratios showing the
      relation between BMI and mental health problems. RESULTS: Compared with their
      nonoverweight counterparts, both white and Hispanic youth who were overweight
      were significantly more likely to report depression or anxiety, feelings of
      worthlessness or inferiority, behavior problems, and bullying of others. Odds
      ratios relating mental health problems and BMI in black subjects were not
      statistically significant except for physician diagnosis of depression.
      CONCLUSIONS: Our results suggest that, when addressing youth overweight status,
      mental health problems also need to be addressed. Given that the relationship
      between mental health problems and youth overweight differs according to
      race/ethnic group, public health programs that target overweight youth should be
      cognizant of potential comorbid mental health problems and that race/ethnicity
      may play a role in the relationship between mental health and overweight status.

PMID- 19171641
TI  - Effects of sleep deprivation on the pediatric electroencephalogram.
AB  - BACKGROUND: The routine electroencephalogram aids in epilepsy syndrome diagnosis.
      Unfortunately, routine outpatient electroencephalogram results are normal in
      roughly half of children with epilepsy. To increase the yield, practice
      guidelines recommend electroencephalograms with sleep and sleep deprivation. The
      purpose of this study was to rigorously evaluate this recommendation in children.
      METHODS: We conducted a randomized, blinded comparison of routine
      electroencephalograms versus sleep-deprived electroencephalograms in 206 children
      aged 0 to 18 years. Electroencephalograms were ordered for standard indications
      after a neurologist's clinical assessment indicated > or =1 seizure (83%) or
      unclear spell (17%). The primary outcome was the proportion of normal routine
      electroencephalogram results versus sleep-deprived electroencephalogram results.
      Logistic regression modeling was used to assess the influence of sleep, as well
      as other clinical factors. RESULTS: Although children with sleep-deprived
      electroencephalograms had less sleep the night before (4.9 vs 7.9 hours) and more
      sleep during electroencephalograms (73% vs 55%), the increase in
      electroencephalogram yield was borderline significant (56% normal sleep-deprived
      electroencephalogram versus 68% normal routine electroencephalogram). Moreover,
      sleep during the electroencephalogram did not increase its diagnostic yield.
      Sleep-deprived electroencephalogram yield tended to be higher in children with
      preelectroencephalogram clinical diagnosis of seizure(s) and at older ages (>3
      years). CONCLUSIONS: Sleep deprivation, but not sleep during the
      electroencephalogram, modestly increases the yield of the electroencephalogram in
      children diagnosed with seizures by neurologists. Compared with a routine
      electroencephalogram, the number needed to test with sleep-deprived
      electroencephalogram to identify 1 additional child with epileptiform discharges
      is approximately 11.

PMID- 19171642
TI  - Lateral sinus thrombosis as a complication of otitis media: 10-year experience at
      the children's hospital of Philadelphia.
AB  - OBJECTIVES: Lateral sinus thrombosis is a rare intracranial complication of
      otitis media that is traditionally described in countries with poor access to
      medical care. Our goal was to describe the clinical presentation, management, and
      outcome of patients diagnosed with lateral sinus thrombosis in a US tertiary care
      center and to highlight the clinically relevant differences in presentation
      between these patients and those described in previous reports. PATIENTS AND
      METHODS: The medical charts of 13 patients diagnosed with otogenic lateral sinus
      thrombosis were reviewed. These patients were identified from a manual search of
      156 subjects with International Classification of Diseases, Ninth Revision codes
      corresponding with a diagnosis of mastoiditis or thromboembolism over a 10-year
      period (1997-2007) at the Children's Hospital of Philadelphia. RESULTS: In
      contrast to previous reports in the literature, the majority of patients in this
      series exhibited cranial neuropathies and signs of raised intracranial pressure.
      Nearly all of the patients had a history of acute otitis media treated with
      antibiotics in the weeks preceding admission. However, many patients denied high
      fevers or active otomastoid symptoms, which are classically associated with
      lateral sinus thrombosis. The diagnosis was made in all of the children by using
      computed tomography and MRI/venography. Treatment strategies included myringotomy
      tube placement, simple mastoidectomy, intravenous antibiotics, and
      anticoagulation. Posthospitalization follow-up data revealed no significant long
      term complications. CONCLUSION: Despite appropriate antibiotic therapy, lateral
      sinus thrombosis and other intracranial complications of otitis media are still a
      threat to children in the modern era. Neurologic, rather than otologic, symptoms
      may dominate the presentation of otogenic lateral sinus thrombosis. Thus, a high
      index of suspicion may be critical for ensuring timely diagnosis of this rare
      condition.

PMID- 19171644
TI  - Can birth weight standards based on healthy populations improve the
      identification of small-for-gestational-age newborns at risk of adverse neonatal
      outcomes?
AB  - OBJECTIVES: To develop neonatal growth standards based on (1) the entire
      population of live births and (2) a healthy subpopulation and compare them in
      identifying infants as small for gestational age and at risk of adverse neonatal
      outcomes. PATIENTS AND METHODS: We included all births, between 28 and 41 weeks
      of gestation, reported in Burgundy (France) from 2000 to 2006. Fetal deaths,
      multiple births, and chromosomal aberrations were excluded. We first estimated
      separate birth weight distributions at each week of gestation for (1) all
      neonates and (2) only infants born from women without maternal diseases. Small
      for gestational age was defined as a birth weight below the 10th percentile of
      the corresponding standard. We assessed the associations of small for gestational
      age on the basis of the alternative definitions, with mortality and major
      neonatal outcomes. RESULTS: We included 127 584 live births. For term newborns,
      small for gestational age was significantly associated with an increased risk of
      death with both standards. In contrast, for preterm newborns (32-36 weeks), small
      for gestational age was not significantly associated with mortality and
      morbidity. Very preterm infants (28-31 weeks) identified as small for gestational
      age according to the healthy-population standard were at higher risk of chronic
      lung disease and intraventricular hemorrhage. When using the entire-population
      standard, small for gestational age was associated with chronic lung disease but
      not intraventricular hemorrhage. The area under the receiver operating
      characteristic for predicting an intraventricular hemorrhage was significantly
      greater for small for gestational age defined with the healthy-population
      standard compared with small for gestational age classified with the entire
      population standard. CONCLUSIONS: Neonatal growth standards based on healthy
      populations could improve the identification of very preterm neonates as small
      for gestational age and at risk of intraventricular hemorrhage.

PMID- 19171645
TI  - Blood pressure responses to psychosocial stress in young adults with very low
      birth weight: Helsinki study of very low birth weight adults.
AB  - Young adults born prematurely with very low birth weight (</=1500 g) have higher
      blood pressure than do their counterparts born at term. We tested whether they
      also have higher blood pressure reactivity to psychosocial stress, which may be a
      more-specific predictor of long-term cardiovascular morbidity. Systolic and
      diastolic blood pressure levels for 44 very low birth weight adults (mean age:
      23.1 years; SD: 2.3 years) and 37 control subjects (mean age: 23.6 years; SD: 2.0
      years) were measured through noninvasive finger photoplethysmography during a
      standardized psychosocial stress challenge (Trier Social Stress Test). Baseline
      and task values and their difference (ie, reactivity) served as outcome
      variables. In comparison with the control group, the very low birth weight group
      had 7.9 mm Hg higher diastolic blood pressure during the task and 4.8 mm Hg
      higher diastolic reactivity, with adjustment for gender and age, height, and BMI
      at testing. A similar trend was seen for systolic blood pressure during the
      baseline period and the task, but the group differences were not statistically
      significant. Our results indicate that very low birth weight is associated with
      elevated blood pressure reactivity to psychosocial stress and, therefore, may
      increase the risk of cardiovascular morbidity.

PMID- 19171643
TI  - Recovery of birth weight z score within 2 years of diagnosis is positively
      associated with pulmonary status at 6 years of age in children with cystic
      fibrosis.
AB  - OBJECTIVE: We recently reported that 60% of children newly diagnosed with cystic
      fibrosis who had pancreatic insufficiency responded to treatment initiation and
      achieved catch-up weight gain to a level comparable with their birth weight z
      score within 2 years of diagnosis ("responders"), whereas the remaining 40%
      failed to do so ("nonresponders"). The present study examined the impact of this
      early weight recovery on subsequent growth pattern and pulmonary status at 6
      years of age. PATIENTS AND METHODS: Sixty-three children with cystic fibrosis who
      had pancreatic insufficiency but no meconium ileus, and were enrolled in the
      Wisconsin Cystic Fibrosis Neonatal Screening Project, were studied. Responders
      were defined by a recovery of weight z score comparable with that at birth within
      2 years of diagnosis. From ages 2 to 6, growth was measured by both height and
      BMI. Pulmonary status was evaluated by symptoms, spirometry, quantitative chest
      radiography, and respiratory microbiology. RESULTS: The majority (71%) of the
      responders maintained their early weight recovery through 6 years of age, whereas
      only 32% of the nonresponders achieved substantial growth improvement from 2 to 6
      years of age. Proportionately fewer responders reported cough symptoms (10%
      daytime cough; 22% nighttime cough) compared with nonresponders (41% daytime
      cough; 45% nighttime cough) at age 6. The percentage of predicted forced
      expiratory volume in 1 second at age 6 was 11% higher in responders (99.5% +/-
      13.9%) compared with nonresponders (88.3% +/- 18.5%). Responders had
      significantly better Brasfield (20.1 +/- 1.4) and Wisconsin chest radiograph (8.3
      +/- 3.3) scores compared with nonresponders (Brasfield: 18.9 +/- 1.8; Wisconsin:
      12.3 +/- 8.3). Respiratory microbiology results were not significantly different.
      Multiple regression analyses indicated that the positive association between
      responder and percent predicted forced expiratory volume in 1 second at 6 years
      of age remained statistically significant after controlling for infections with
      Pseudomonas aeruginosa and Staphylococcus aureus and chest radiograph scores.
      Growth patterns from 2 to 6 years of age were not associated with pulmonary
      measures at age 6. CONCLUSIONS: Patients with cystic fibrosis with pancreatic
      insufficiency who achieved early growth recovery within 2 years of diagnosis had
      fewer cough symptoms, higher lung function, and better chest radiograph scores at
      6 years of age.

PMID- 19171646
TI  - Interleukin-1beta-induced disruption of barrier function in cultured human
      corneal epithelial cells.
AB  - PURPOSE: The barrier function of the corneal epithelium contributes to corneal
      homeostasis and is impaired by inflammation. Adherens junctions (AJs) and tight
      junctions (TJs) of the corneal epithelium are essential for cell adhesion and
      barrier function. We examined the effects of the proinflammatory cytokine
      interleukin (IL)-1beta on AJs and TJs as well as on barrier function in simian
      virus 40-transformed human corneal epithelial (HCE) cells. METHODS: Barrier
      function was evaluated by measurement of transepithelial electrical resistance
      (TER). The subcellular distributions of the AJ proteins E-cadherin and beta
      catenin, the TJ proteins ZO-1 and occludin, and the p65 subunit of nuclear factor
      (NF)-kappaB were determined by immunofluorescence staining. The expression of
      junctional proteins as well as the phosphorylation and degradation of the NF
      kappaB-inhibitory protein IkappaB-alpha were examined by immunoblot analysis.
      RESULTS: IL-1beta induced the disappearance of ZO-1 and occludin from the
      interfaces of neighboring HCE cells without affecting the localization of E
      cadherin or beta-catenin. It also reduced the TER of HCE cells in a concentration
      and time-dependent manner. The overall abundance of TJ and AJ proteins was not
      affected by IL-1beta. IL-1beta induced the phosphorylation and downregulation of
      IkappaB-alpha as well as the translocation of p65 to the nucleus. The NF-kappaB
      inhibitor curcumin blocked the effects of IL-1beta on both TER and the
      subcellular localization of ZO-1 and occludin. CONCLUSIONS: IL-1beta induced the
      redistribution of ZO-1 and occludin from TJs of HCE cells and thereby disrupted
      the barrier function of these cells in a manner dependent on NF-kappaB. These
      effects of IL-1beta may contribute to the loss of corneal epithelial barrier
      function associated with ocular inflammation.

PMID- 19171647
TI  - Expression of matrix metalloproteinases during experimental Candida albicans
      keratitis.
AB  - PURPOSE: This study was designed to investigate the expression of matrix
      metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs)
      during the inception and progression of experimental keratomycosis. METHODS:
      Scarified corneas of adult BALB/c mice were topically inoculated with Candida
      albicans strain SC5314 and monitored for disease severity. Infected and mock
      infected corneas were compared at 1 day post inoculation (p.i.) with a murine
      gene microarray. Real-time reverse transcriptase-polymerase chain reaction (RT
      PCR) determined MMP and TIMP levels at 1, 3, and 7 days p.i. for infected, mock
      infected, and normal corneas. Immunostaining localized target proteins at 1 day
      p.i. RESULTS: Eyes inoculated with C. albicans developed corneal infection with a
      mean clinical score of 8.2+/-0.8 at 1 day p.i. Compared to controls at 1 day
      p.i., MMP-8, -9, -10, -12, -13, -19, and TIMP-1 were significantly upregulated
      from fivefold to 375-fold by microarray and from threefold to 78-fold by real
      time RT-PCR. Upregulated MMPs and TIMP-1 in the corneal epithelium and stroma of
      infected eyes correlated with the influx of acute inflammatory cells. Neither MMP
      8 nor -13 expression was affected by mechanical trauma, but both increased >100
      fold during the week after the onset of fungal keratitis. TIMP-1 expression rose
      from 21-fold more than controls at 1 day to 46-fold at 7 days p.i. by RT-PCR.
      CONCLUSIONS: Transcriptional and translational levels of MMP-8, -9, -13, and TIMP
      1 increase during the early stages of C. albicans keratitis, confirming findings
      for MMP-9 and TIMP-1 in other infectious keratitis models and suggesting roles
      for MMP-8 and -13.

PMID- 19171648
TI  - Subtoxic oxidative stress induces senescence in retinal pigment epithelial cells
      via TGF-beta release.
AB  - PURPOSE: The goal of the present study was to determine whether oxidative stress
      and transforming growth factor (TGF)-beta induce cellular senescence in human
      retinal pigment epithelial (RPE) cells. METHODS: Cultured human RPE cells were
      exposed to 50 to 150 microM hydrogen peroxide (H(2)O(2)) for 1 and 2 hours or
      treated with 1.0 ng/mL TGF-beta1 or -beta2 for 12, 24, and 48 hours. Senescence
      associated beta-galactosidase (SA-beta-Gal) activity was detected by
      histochemical staining. Expression of senescence-associated genes (apolipoprotein
      J [Apo J], connective tissue growth factor [CTGF], fibronectin, and SM22) was
      examined by real-time PCR and induction of signal transduction proteins (p21,
      p16, and pRb) by Western blot analysis. The effects of TGF-beta blocking on the
      oxidative stress-induced expression of senescence-associated biomarkers were
      investigated by simultaneous incubation with neutralizing antibodies against the
      TGF-beta1, -beta2, and -beta3 isoforms and the TGF-betaII receptor. RESULTS:
      H(2)O(2) markedly increased the number of SA-beta-Gal-positive cells to up to 89%
      and the expression of Apo J, CTGF, fibronectin, and SM22 by approximately three
      to fourfold. Treatment with TGF-beta1 and -beta2 showed similar changes.
      H(2)O(2)and TGF-beta1 and -beta2 markedly enhanced the expression of p21 but
      downregulated pRb. In contrast, they had no effect on p16 expression.
      Simultaneous treatment with neutralizing antibodies against the TGF-beta1, 
      beta2, and -beta3 isoforms and the TGF-betaII receptor prevented the oxidative
      stress-mediated elevation of senescence-associated biomarkers. CONCLUSIONS:
      Oxidative stress, TGF-beta1, and TGF-beta2 are capable of inducing cellular
      senescence in cultured human RPE cells. Therefore, reduction of oxidative stress
      and minimizing TGF-beta may help to prevent senescence-associated changes in the
      RPE as seen in early age-related macular degeneration.

PMID- 19171649
TI  - Divergent regulation of cardiac KCND3 potassium channel expression by the thyroid
      hormone receptors alpha1 and beta1.
AB  - The cardiac transient outward current I(to) is regulated by thyroid hormone (T3).
      However, it remains unclear whether T3 directly modulates underlying gene
      transcription and which thyroid receptor (TR) isoform might be responsible for
      gene transactivation. To clarify this situation, we analysed the role of T3 and
      its receptors alpha1 (TRalpha1) and beta1 (TRbeta1) in regulation of KCNA4,
      KCND2, KCND3 and KCNIP2 transcription in rat cardiomyocytes. Initial results
      demonstrated a T3-mediated increase of I(to) current density. T3 stimulation
      enhanced KCND2 and KCND3 expression and decreased KCNA4 transcription, while
      KCNIP2 remained unaffected. To dissect the role of TRalpha1 and TRbeta1 in T3
      dependent I(to) modulation, TRalpha1 and TRbeta1 were overexpressed in
      cardiomyocytes by adenovirus-mediated gene transfer. TRalpha1 increased I(to),
      while TRbeta1 significantly reduced I(to) in size, which was associated with
      TRalpha1-mediated increase and TRbeta1-mediated reduction of KCND2/3
      transcription. To further evaluate a possible direct interaction of TRalpha1 and
      TRbeta1 with the KCND3 promoter, TR expression vectors were cotransfected with a
      construct containing 2335 bp of the KCND3 5'-flanking sequence linked to a
      luciferase reporter into ventricular myocytes. While the TRalpha1 aporeceptor
      enhanced KCND3 transcription, the TRbeta1 aporeceptor suppressed KCND3
      expression, with both effects exhibiting ligand-dependent amplification upon T3
      stimulation. Deletion of the KCND3 5'-flanking region localized the suppressible
      promoter sequence for TRbeta1 to within -293 bp and the activating promoter
      sequence for TRalpha1 to within -2335 to -1654 bp of the transcription start
      site. Disruption of putative TR binding sites by mutagenesis abolished the
      TRalpha1- (G-1651T) and TRbeta1- (G-73T) mediated effects, indicating that
      TRalpha1 and TRbeta1 response elements map to different regions of the KCND3
      promoter. Thus, I(to) is modulated by diverse T3-dependent regulation of
      underlying gene transcription. TRalpha1 and TRbeta1 exhibit distinct effects on
      KCND3 transactivation with TRalpha1 enhancing and TRbeta1 suppressing KCND3
      transcription.

PMID- 19171650
TI  - Synaptotagmin-7 is a principal Ca2+ sensor for Ca2+ -induced glucagon exocytosis
      in pancreas.
AB  - Hormones such as glucagon are secreted by Ca(2+)-induced exocytosis of large
      dense-core vesicles, but the mechanisms involved have only been partially
      elucidated. Studies of pancreatic beta-cells secreting insulin revealed that
      synaptotagmin-7 alone is not sufficient to mediate Ca(2+)-dependent insulin
      granule exocytosis, and studies of chromaffin cells secreting neuropeptides and
      catecholamines showed that synaptotagmin-1 and -7 collaborate as Ca(2+) sensors
      for exocytosis, and that both are equally involved. As no other peptide secretion
      was analysed, it remains unclear whether synaptotagmins generally act as Ca(2+)
      sensors in large dense-core vesicle exocytosis in endocrine cells, and if so,
      whether synaptotagmin-7 always functions with a partner in that role. In
      particular, far less is known about the mechanisms underlying Ca(2+)-triggered
      glucagon release from alpha-cells than insulin secretion from beta-cells, even
      though insulin and glucagon together regulate blood glucose levels. To address
      these issues, we analysed the role of synaptotagmins in Ca(2+)-triggered glucagon
      exocytosis. Surprisingly, we find that deletion of a single synaptotagmin
      isoform, synaptotagmin-7, nearly abolished Ca(2+)-triggered glucagon secretion.
      Moreover, single-cell capacitance measurements confirmed that pancreatic alpha
      cells lacking synaptotagmin-7 exhibited little Ca(2+)-induced exocytosis, whereas
      all other physiological and morphological parameters of the alpha-cells were
      normal. Our data thus identify synaptotagmin-7 as a principal Ca(2+) sensor for
      glucagon secretion, and support the notion that synaptotagmins perform a
      universal but selective function as individually acting Ca(2+) sensors in
      neurotransmitter, neuropeptide, and hormone secretion.

PMID- 19171651
TI  - Experimentally guided modelling of dendritic excitability in rat neocortical
      pyramidal neurones.
AB  - Constructing physiologically relevant compartmental models of neurones is
      critical for understanding neuronal activity and function. We recently suggested
      that measurements from multiple locations along the soma, dendrites and axon are
      necessary as a data set when using a genetic optimization algorithm to constrain
      the parameters of a compartmental model of an entire neurone. However, recordings
      from L5 pyramidal neurones can routinely be performed simultaneously from only
      two locations. Now we show that a data set recorded from the soma and apical
      dendrite combined with a parameter peeling procedure is sufficient to constrain a
      compartmental model for the apical dendrite of L5 pyramidal neurones. The peeling
      procedure was tested on several compartmental models showing that it avoids local
      minima in parameter space. Based on the requirements of this analysis procedure,
      we designed and performed simultaneous whole-cell recordings from the soma and
      apical dendrite of rat L5 pyramidal neurones. The data set obtained from these
      recordings allowed constraining a simplified compartmental model for the apical
      dendrite of L5 pyramidal neurones containing four voltage-gated conductances. In
      agreement with experimental findings, the optimized model predicts that the
      conductance density gradients of voltage-gated K(+) conductances taper rapidly
      proximal to the soma, while the density gradient of the voltage-gated Na(+)
      conductance tapers slowly along the apical dendrite. The model reproduced the
      back-propagation of the action potential and the modulation of the resting
      membrane potential along the apical dendrite. Furthermore, the optimized model
      provided a mechanistic explanation for the back-propagation of the action
      potential into the apical dendrite and the generation of dendritic Na(+) spikes.

PMID- 19171652
TI  - Action potential initiation in the peripheral terminals of cold-sensitive
      neurones innervating the guinea-pig cornea.
AB  - The site at which action potentials initiate within the terminal region of
      unmyelinated sensory axons has not been resolved. Combining recordings of nerve
      terminal impulses (NTIs) and collision analysis, the site of action potential
      initiation in guinea-pig corneal cold receptors was determined. For most
      receptors (77%), initiation mapped to a point in the time domain that was closer
      to the nerve terminal than to the site of electrical stimulation at the back of
      the eye. Guinea-pig corneal cold receptors are Adelta-neurones that lose their
      myelin sheath at the point where they enter the cornea, and therefore their axons
      conduct more slowly within the cornea. Allowing for this inhomogeneity in
      conduction speed, the resulting spatial estimates of action potential initiation
      sites correlated with changes in NTI shape predicted by simulation of action
      potentials initiating within a nerve terminal. In some receptors, more than one
      NTI shape was observed. Simulations of NTI shape suggest that the origin of
      differing NTI shapes result from action potentials initiating at different,
      spatially discrete, locations within the nerve terminal. Importantly, the
      relative incidence of NTI shapes resulting from action potential initiation close
      to the nerve termination increased during warming when nerve activity decreased,
      indicating that the favoured site of action potential initiation shifts toward
      the nerve terminal when it hyperpolarizes. This finding can be explained by a
      hyperpolarization-induced relief of Na(+) channel inactivation in the nerve
      terminal. The results provide direct evidence that the molecular entities
      responsible for stimulus transduction and action potential initiation reside in
      parallel with one another in the unmyelinated nerve terminals of cold receptors.

PMID- 19171653
TI  - Activity-dependent depression of the spike after-depolarization generates long
      lasting intrinsic plasticity in hippocampal CA3 pyramidal neurons.
AB  - Persistent plastic changes to the intrinsic excitability of neurons have
      substantial implications for computational processing within the CNS. We have
      identified and characterized a novel long-lasting form of intrinsic plasticity in
      hippocampal CA3 pyramidal cells. Although the patterns of action potential firing
      elicited in this cell population by depolarizing current injections exhibited
      considerable diversity, practically all cells produced an initial high frequency
      (>100 Hz) burst of two to five spikes. This burst involved conductances that were
      responsible for the prominent spike afterdepolarization of CA3 pyramids. Long
      lasting changes in the firing behaviour of CA3 cells were produced by
      conditioning stimuli (CS) consisting of either periods of depolarization in
      voltage clamp or periods of short (2 or 4 spikes) high frequency (circa 100 Hz)
      burst firing at 5 or 10 Hz. CS-induced changes included substantial prolongation
      of the first inter-spike interval and increased spike jitter. Similar CS-induced
      changes were seen when the test stimulus used to elicit firing resembled a
      glutamatergic EPSC. In line with this, a long-lasting depression of the ADP was
      elicited by the same CS that altered firing patterns of CA3 cells. Conditioning
      induced changes in both spiking patterns and ADP amplitude were blocked by
      buffering intracellular Ca(2+) with BAPTA. Furthermore, the Kv7 channel blocker
      XE991, a cognitive enhancer, both enhanced the ADP and completely eliminated its
      conditioning-induced depression. These findings indicate that a persistent
      enhancement of Kv7 channels, following a transient increase in cytoplasmic
      Ca(2+), results in a prolonged depression of the ADP in CA3 pyramidal neurones.

PMID- 19171654
TI  - Visual control of stable and unstable loads: what is the feedback delay and
      extent of linear time-invariant control?
AB  - Human balance is commonly described using linear-time-invariant (LTI) models. The
      feedback time delay determines the position of balance in the motor-control
      hierarchy. The extent of LTI control illuminates the automaticity of the control
      process. Using non-parametric analysis, we measured the feedback delay, extent of
      LTI control and visuo-motor transfer function in six randomly disturbed, visuo
      manual compensatory tracking tasks analogous to standing with small mechanical
      perturbations and purely visual information. The delay depended primarily on load
      order (2nd: 220+/-30 ms, 1st: 124+/-20 ms), and secondarily on visual
      magnification (extent 2nd: 34 ms, 1st: 8 ms) and was unaffected by load
      stability. LTI control explained 1st order and stable loads relatively well. For
      unstable (85% passive stabilisation) 2nd order loads, LTI control accounted for
      40% of manual output at 0.1 Hz decreasing below 10% as frequency increased
      through the important 1-3 Hz region where manual power and visuo-motor gain are
      high. Visual control of unstable 2nd order loads incurs substantial feedback
      delays and the control process will not be LTI. These features do not result from
      exclusive use of visual inputs because we found much shorter delays and a greater
      degree of LTI control when subjects visually controlled a 1st order load. Rather,
      these results suggest that delay and variability are inevitable when more
      flexible, intentional mechanisms are required to control 2nd order unstable
      loads. The high variability of quiet standing, and movement generally, may be
      indicative of flexible, variable delay, intentional mechanisms rather than the
      automatic LTI responses usually reported in response to large perturbations.

PMID- 19171655
TI  - Mechanistic basis of differential conduction in skeletal muscle arteries.
AB  - The goal of this investigation was to probe intercellular conduction in skeletal
      muscle feed arteries and to address why smooth muscle-initiated responses fail to
      robustly spread like their endothelial counterpart. Using computational and
      experimental approaches, two interrelated rationales were developed to explain
      this apparent discrepancy in cell-to-cell communication. The first rationale
      stressed that smooth muscle electrical responses, if initiated, will be actively
      dissipated as they spread from cell-to-cell along the arterial wall. Charge
      dissipation is promoted within arteries by the structural and connectivity
      properties of vascular cells. The second rationale centred on the idea that when
      agents other than KCl stimulate a limited number of smooth muscle cells, they
      fail to generate the currents required to elicit a localized membrane potential
      (V(M)) response. This insufficiency results in part from charge loss, via gap
      junctions, to neighbouring unstimulated cells. Experiments confirmed the latter
      rationale by showing that focal phenylephrine application: (1) elicited a
      localized constriction insensitive to L-type Ca(2+) channel blockade; and (2)
      failed to substantially depolarize vascular smooth muscle cells. Further
      investigation revealed that while focal phenylephrine-induced constriction was
      V(M) independent, it was reliant on internal Ca(2+) mobilization and the
      activation of inositol 1,4,5-trisphosphate (IP(3)) receptors. The preceding
      findings illustrate that by using computational modelling and experimentation in
      a complementary manner, one can isolate key cellular properties and rationally
      examine their role in limiting the conduction of smooth muscle-initiated
      responses. Functionally, these observations enable investigators to assign the
      concept of 'local and global' blood flow control to the electrical and/or non
      electrical behaviour of specific cell types.

PMID- 19171656
TI  - Phenomics of cardiac chloride channels: the systematic study of chloride channel
      function in the heart.
AB  - Recent studies have identified several chloride (Cl-) channel genes in the heart,
      including CFTR, ClC-2, ClC-3, CLCA, Bestrophin, and TMEM16A. Gene targeting and
      transgenic techniques have been used to delineate the functional role of cardiac
      Cl- channels in the context of health and disease. It has been shown that Cl-
      channels may contribute to cardiac arrhythmogenesis, myocardial hypertrophy and
      heart failure, and cardioprotection against ischaemia-reperfusion. The study of
      physiological or pathophysiological phenotypes of cardiac Cl- channels, however,
      may be complicated by the compensatory changes in the animals in response to the
      targeted genetic manipulation. Alternatively, tissue-specific conditional or
      inducible knockout or knockin animal models may be more valuable in the
      phenotypic studies of specific Cl- channels by limiting the effect of
      compensation on the phenotype. The integrated function of Cl- channels may
      involve multi-protein complexes of the Cl- channel subproteome and similar
      phenotypes can be attained from alternative protein pathways within cellular
      networks, which are influenced by genetic and environmental factors. Therefore,
      the phenomics approach, which characterizes phenotypes as a whole phenome and
      systematically studies the molecular changes that give rise to particular
      phenotypes achieved by modifying the genotype (such as gene knockouts or
      knockins) under the scope of genome/proteome/phenome, may provide a more complete
      understanding of the integrated function of each cardiac Cl- channel in the
      context of health and disease.

PMID- 19171657
TI  - Pathophysiology and puzzles of the volume-sensitive outwardly rectifying anion
      channel.
AB  - Cell swelling activates or upregulates a number of anion channels. Of the volume
      activated or -regulated anion channels (VAACs or VRACs), the volume-sensitive
      outwardly rectifying anion channel (VSOR) is most prominently activated and
      ubiquitously expressed. This channel is known to be involved in a variety of
      physiological processes including cell volume regulation, cell proliferation,
      differentiation and cell migration as well as cell turnover involving apoptosis.
      Recent studies have shown that VSOR activity is also involved in a number of
      pathophysiological processes including the acquisition of cisplatin resistance by
      cancer cells, ischaemia-reperfusion-induced death of cardiomyocytes and
      hippocampal neurons, glial necrosis under lactacidosis as well as neuronal
      necrosis under excitotoxicity. Moreover, VSOR serves as the pathway for glutamate
      release from astrocytes under ischaemic conditions and when stimulated by
      bradykinin, an initial mediator of inflammation. So far, many signalling
      molecules including the EGF receptor, PI3K, Src, PLCgamma and Rho/Rho kinase have
      been implicated in the regulation of VSOR activity. However, our pharmacological
      studies suggest that these signals are not essential components of the swelling
      induced VSOR activation mechanism even though some of these signals may play
      permissive or modulatory roles. Molecular identification of VSOR is required to
      address the question of how cells sense volume expansion and activate VSOR.

PMID- 19171658
TI  - Asymmetric control of inspiratory and expiratory phases by excitability in the
      respiratory network of neonatal mice in vitro.
AB  - Rhythmic motor behaviours consist of alternating movements, e.g. swing-stance in
      stepping, jaw opening and closing during chewing, and inspiration-expiration in
      breathing, which must be labile in frequency, and in some cases, in the duration
      of individual phases, to adjust to physiological demands. These movements are the
      expression of underlying neural circuits whose organization governs the
      properties of the motor behaviour. To determine if the ability to operate over a
      broad range of frequencies in respiration is expressed in the rhythm generator,
      we isolated the kernel of essential respiratory circuits using rhythmically
      active in vitro slices from neonatal mice. We show respiratory motor output in
      these slices at very low frequencies (0.008 Hz), well below the typical frequency
      in vitro (approximately 0.2 Hz) and in most intact normothermic mammals. Across
      this broad range of frequencies, inspiratory motor output bursts remained
      remarkably constant in pattern, i.e. duration, peak amplitude and area. The
      change in frequency was instead attributable to increased interburst interval,
      and was largely unaffected by removal of fast inhibitory transmission. Modulation
      of the frequency was primarily achieved by manipulating extracellular potassium,
      which significantly affects neuronal excitability. When excitability was lowered
      to slow down, or in some cases stop, spontaneous rhythm, brief stimulation of the
      respiratory network with a glutamatergic agonist could evoke (rhythmic) motor
      output. In slices with slow (<0.02 Hz) spontaneous rhythms, evoked motor output
      could follow a spontaneous burst at short (<or=1 s) or long (approximately 60 s)
      intervals. The intensity or timing of stimulation determined the latency to the
      first evoked burst, with no evidence for a refractory period greater than
      approximately 1 s, even with interburst intervals >60 s. We observed during
      inspiration a large magnitude (approximately 0.6 nA) outward current generated by
      Na(+)/K(+) ATPase that deactivated in 25-100 ms and thus could contribute to
      burst termination and the latency of evoked bursts but is unlikely to control the
      interburst interval. We propose that the respiratory network functions over a
      broad range of frequencies by engaging distinct mechanisms from those controlling
      inspiratory duration and pattern that specifically govern the interburst
      interval.

PMID- 19171659
TI  - In vitro characterization of HCN channel kinetics and frequency dependence in
      myocytes predicts biological pacemaker functionality.
AB  - The pacemaker current, mediated by hyperpolarization-activated cyclic nucleotide
      gated (HCN) channels, contributes to the initiation and regulation of cardiac
      rhythm. Previous experiments creating HCN-based biological pacemakers in vivo
      found that an engineered HCN2/HCN1 chimeric channel (HCN212) resulted in
      significantly faster rates than HCN2, interrupted by 1-5 s pauses. To elucidate
      the mechanisms underlying the differences in HCN212 and HCN2 in vivo
      functionality as biological pacemakers, we studied newborn rat ventricular
      myocytes over-expressing either HCN2 or HCN212 channels. The HCN2- and HCN212
      over-expressing myocytes manifest similar voltage dependence, current density and
      sensitivity to saturating cAMP concentrations, but HCN212 has faster
      activation/deactivation kinetics. Compared with HCN2, myocytes expressing HCN212
      exhibit a faster spontaneous rate and greater incidence of irregular rhythms
      (i.e. periods of rapid spontaneous rate followed by pauses). To explore these
      rhythm differences further, we imposed consecutive pacing and found that
      activation kinetics of the two channels are slower at faster pacing frequencies.
      As a result, time-dependent HCN current flowing during diastole decreases for
      both constructs during a train of stimuli at a rapid frequency, with the effect
      more pronounced for HCN2. In addition, the slower deactivation kinetics of HCN2
      contributes to more pronounced instantaneous current at a slower frequency. As a
      result of the frequency dependence of both instantaneous and time-dependent
      current, HCN2 exhibits more robust negative feedback than HCN212, contributing to
      the maintenance of a stable pacing rhythm. These results illustrate the benefit
      of screening HCN constructs in spontaneously active myocyte cultures and may
      provide the basis for future optimization of HCN-based biological pacemakers.

PMID- 19171666
TI  - Advancing the 'science of delivery' of health promotion: not just the 'science of
      discovery'.

PMID- 19171660
TI  - Cardiovascular and thermal responses evoked from the periaqueductal grey require
      neuronal activity in the hypothalamus.
AB  - Stimulation of neurons in the lateral/dorsolateral periaqueductal grey (l/dlPAG)
      produces increases in heart rate (HR) and mean arterial pressure (MAP) that are,
      according to traditional views, mediated through projections to medullary
      autonomic centres and independent of forebrain mechanisms. Recent studies in rats
      suggest that neurons in the l/dlPAG are downstream effectors responsible for
      responses evoked from the dorsomedial hypothalamus (DMH) from which similar
      cardiovascular changes and increase in core body temperature (T(co)) can be
      elicited. We hypothesized that, instead, autonomic effects evoked from the
      l/dlPAG depend on neuronal activity in the DMH. Thus, we examined the effect of
      microinjection of the neuronal inhibitor muscimol into the DMH on increases in
      HR, MAP and T(co) produced by microinjection of N-methyl-D-aspartate (NMDA) into
      the l/dlPAG in conscious rats. Microinjection of muscimol alone modestly
      decreased baseline HR and MAP but failed to alter T(co). Microinjection of NMDA
      into the l/dlPAG caused marked increases in all three variables, and these were
      virtually abolished by prior injection of muscimol into the DMH. Similar
      microinjection of glutamate receptor antagonists into the DMH also suppressed
      increases in HR and abolished increases in T(co) evoked from the PAG. In
      contrast, microinjection of muscimol into the hypothalamic paraventricular
      nucleus failed to reduce changes evoked from the PAG and actually enhanced the
      increase in T(co). Thus, our data suggest that increases in HR, MAP and T(co)
      evoked from the l/dlPAG require neuronal activity in the DMH, challenging
      traditional views of the place of the PAG in central autonomic neural circuitry.

PMID- 19171667
TI  - The DREAM model's effectiveness in health promotion of AIDS patients in Africa.
AB  - This study evaluates the effectiveness of a holistic model for treating people
      living with AIDS in Africa; the model aims to improve knowledge about AIDS
      prevention and care, increase trust in the health centre, impact behaviour, and
      promote a high level of adherence to HAART. The study took place in the context
      of the DREAM (Drug Resource Enhancement against AIDS and Malnutrition) programme
      in Mozambique, designed by the Community of Sant'Egidio to treat HIV patients in
      Africa. It provides patients with free anti-retroviral drugs, laboratory tests
      (including viral load), home care and nutritional support. This is a prospective
      study involving 531 patients over a 12-month period. The patients, predominantly
      poor and with a low level of education, demonstrated a good level of knowledge
      about AIDS (more than 90% know how it is transmitted) and trust in the treatment,
      with a relatively small percentage turning to traditional healers. Overall the
      patients had a low level of engaging in risky sexual behaviour and a very good
      level of adherence to HAART (69.5% of the 531 subjects had a pill count higher
      than 95%). The positive results of the programme's educational initiatives were
      confirmed with the patients' good clinical results.

PMID- 19171668
TI  - Six essential roles of health promotion research centres: the Atlantic Canada
      experience.
AB  - Over the past 20 years, the federal government and universities across Canada
      have directed resources towards the development of university-based health
      promotion research centres. Researchers at health promotion research centres in
      Canada have produced peer-reviewed papers and policy documents based on their
      work, but no publications have emerged that focus on the specific roles of the
      health promotion research centres themselves. The purpose of this paper is to
      propose a framework, based on an in-depth examination of one centre, to help
      identify the unique roles of health promotion research centres and to clarify the
      value they add to promoting health and advancing university goals. Considering
      the shifting federal discourse on health promotion over time and the
      vulnerability of social and health sciences to changes in research funding
      priorities, health promotion research centres in Canada and elsewhere may need to
      articulate their unique roles and contributions in order to maintain a critical
      focus on health promotion research. The authors briefly describe the Atlantic
      Health Promotion Research Centre (AHPRC), propose a framework that illustrates
      six essential roles of health promotion research centres and describe the policy
      contexts and challenges of health promotion research centres. The analysis of
      research and knowledge translation activities over 15 years at AHPRC sheds light
      on the roles that health promotion research centres play in applied research. The
      conclusion raises questions regarding the value of university-based research
      centres and challenges to their sustainability.

PMID- 19171669
TI  - Water, ecology and health: ecosystems as settings for promoting health and
      sustainability.
AB  - Despite the proposed ecological and systems-based perspectives of the settings
      based approach to health promotion, most initiatives have tended to overlook the
      fundamental nature of ecosystems. This paper responds to this oversight by
      proposing an explicit re-integration of ecosystems within the healthy settings
      approach. We make this case by focusing on water as an integrating unit of
      analysis. Water, on which all life depends, is not only an integral consideration
      for the existing healthy settings (schools, hospitals, workplaces) but also
      highlights the ecosystem context of health and sustainability. A focus on
      catchments (also know as watersheds and river basins) exemplifies the scaled and
      upstream/downstream nature of ecosystems and draws into sharp focus the cross
      sectoral and transdisciplinary context of the social and environmental
      determinants of health. We position this work in relation to the converging
      agendas of health promotion and ecosystem management at the local, regional and
      global scales--and draw on evidence from international initiatives as diverse as
      the WHO Commission on Social Determinants of Health, and the Millennium Ecosystem
      Assessment. Using water as a vehicle for understanding the systemic context for
      human wellbeing, health promotion and disease prevention draws inevitable
      attention to key challenges of scale, intersectoral governance and the
      complementary themes of promoting resilience and preventing vulnerability. We
      conclude by highlighting the importance of building individual and institutional
      capacity for this kind of integration--equipping a new generation of researchers,
      practitioners and decision-makers to be conversant with the language of
      ecosystems, capable of systemic thought and focused on settings that can promote
      both health and sustainability.

PMID- 19171671
TI  - Calcium signaling by dopamine D5 receptor and D5-D2 receptor hetero-oligomers
      occurs by a mechanism distinct from that for dopamine D1-D2 receptor hetero
      oligomers.
AB  - In this report, we investigated whether the D5 dopamine receptor, given its
      structural and sequence homology with the D1 receptor, could interact with the D2
      receptor to mediate a calcium signal similar to the G(q/11) protein-linked
      phospholipase C-mediated calcium signal resulting from the coactivation of D1 and
      D2 dopamine receptors within D1-D2 receptor heterooligomers. Fluorescent
      resonance energy transfer experiments demonstrated close colocalization of cell
      surface D5 and D2 receptors (<100 A), indicating hetero-oligomerization of D5 and
      D2 receptors in cells coexpressing both receptors. Coactivation of D5 and D2
      receptors within the D5-D2 hetero-oligomers activated a calcium signal. However,
      unlike what is observed for D1 receptors, which activate extensive calcium
      mobilization only within a complex with the D2 receptors, a robust calcium signal
      was triggered by D5 receptors expressed alone. Hetero-oligomerization with the D2
      receptor attenuated the ability of the D5 receptor to trigger a calcium signal.
      The D5 and D5-D2-associated calcium signals were G(q/11) protein-linked and
      phospholipase C-mediated but were also critically dependent on the influx of
      extracellular calcium through store-operated calcium channels, unlike the calcium
      release triggered by D1-D2 heterooligomers. Collectively, these results
      demonstrate that calcium signaling through D5-D2 receptor hetero-oligomers
      occurred through a distinct mechanism to achieve an increase in intracellular
      calcium levels.

PMID- 19171672
TI  - Capacitative Ca2+ entry via Orai1 and stromal interacting molecule 1 (STIM1)
      regulates adenylyl cyclase type 8.
AB  - Capacitative Ca(2+) entry (CCE), which occurs through the plasma membrane as a
      result of Ca(2+) store depletion, is mediated by stromal interacting molecule 1
      (STIM1), a sensor of intracellular Ca(2+) store content, and the pore-forming
      component Orai1. However, additional factors, such as C-type transient receptor
      potential (TRPC) channels, may also participate in the CCE apparatus. To explore
      whether the store-dependent Ca(2+) entry reconstituted by coexpression of Orai1
      and STIM1 has the functional properties of CCE, we used the Ca(2+)-calmodulin
      stimulated adenylyl cyclase type 8 (AC8), which responds selectively to CCE,
      whereas other modes of Ca(2+) entry, including those activated by arachidonate
      and the ionophore ionomycin, are ineffective. In addition, the Ca(2+) entry
      mediated by previous CCE candidates, diacylglycerol-activated TRPC channels, does
      not activate AC8. Here, we expressed Orai1 and STIM1 in HEK293 cells and saw a
      robust increment in CCE, and a proportional increase in CCE-stimulated AC8
      activity. Inhibitors of the CCE assembly process ablated the effects on cyclase
      activity in both AC8-overexpressing HEK293 cells and insulin-secreting MIN6 cells
      endogenously expressing Ca(2+)-sensitive AC isoforms. AC8 is believed to be
      closely associated with the source of CCE; indeed, not only were AC8, Orai1, and
      STIM1 colocalized at the plasma membrane but also all three proteins occurred in
      lipid rafts. Together, our data indicate that Orai1 and STIM1 can be integral
      components of the cAMP and CCE microdomain associated with adenylyl cyclase type
      8.

PMID- 19171674
TI  - A cytochrome P450-derived epoxygenated metabolite of anandamide is a potent
      cannabinoid receptor 2-selective agonist.
AB  - Oxidation of the endocannabinoid anandamide by cytochrome P450 (P450) enzymes has
      the potential to affect signaling pathways within the endocannabinoid system and
      pharmacological responses to novel drug candidates targeting this system. We
      previously reported that the human cytochromes P450 2D6, 3A4, and 4F2 are high
      affinity, high-turnover anandamide oxygenases in vitro, forming the novel
      metabolites hydroxyeicosatetraenoic acid ethanolamides and epoxyeicosatrienoic
      acid ethanolamides. The objective of this study was to investigate the possible
      biological significance of these metabolic pathways. We report that the 5,6
      epoxide of anandamide, 5,6-epoxyeicosatrienoic acid ethanolamide (5,6-EET-EA), is
      a potent and selective cannabinoid receptor 2 (CB2) agonist. The K(i) values for
      the binding of 5,6-EET-EA to membranes from Chinese hamster ovary (CHO) cells
      expressing either recombinant human CB1 or CB2 receptor were 11.4 microM and 8.9
      nM, respectively. In addition, 5,6-EET-EA inhibited the forskolin-stimulated
      accumulation of cAMP in CHO cells stably expressing the CB2 receptor (IC(50) =
      9.8 +/- 1.3 nM). Within the central nervous system, the CB2 receptor is expressed
      on activated microglia and is a potential therapeutic target for
      neuroinflammation. BV-2 microglial cells stimulated with low doses of interferon
      gamma exhibited an increased capacity for converting anandamide to 5,6-EET-EA,
      which correlated with increased protein expression of microglial P450 4F and 3A
      isoforms. Finally, we demonstrate that 5,6-EET-EA is more stable than anandamide
      in mouse brain homogenates and is primarily metabolized by epoxide hydrolase.
      Combined, our results suggest that epoxidation of anandamide by P450s to form 5,6
      EET-EA represents an endocannabinoid bioactivation pathway in the context of
      immune cell function.

PMID- 19171673
TI  - Nitrooleic acid, an endogenous product of nitrative stress, activates nociceptive
      sensory nerves via the direct activation of TRPA1.
AB  - Transient Receptor Potential A1 (TRPA1) is a nonselective cation channel,
      preferentially expressed on a subset of nociceptive sensory neurons, that is
      activated by a variety of reactive irritants via the covalent modification of
      cysteine residues. Excessive nitric oxide during inflammation (nitrative stress),
      leads to the nitration of phospholipids, resulting in the formation of highly
      reactive cysteine modifying agents, such as nitrooleic acid (9-OA-NO(2)). Using
      calcium imaging and electrophysiology, we have shown that 9-OA-NO(2) activates
      human TRPA1 channels (EC(50), 1 microM), whereas oleic acid had no effect on
      TRPA1. 9-OA-NO(2) failed to activate TRPA1 in which the cysteines at positions
      619, 639, and 663 and the lysine at 708 had been mutated. TRPA1 activation by 9
      OA-NO(2) was not inhibited by the NO scavenger carboxy-PTIO. 9-OA-NO(2) had no
      effect on another nociceptive-specific ion channel, TRPV1. 9-OA-NO(2) activated a
      subset of mouse vagal and trigeminal sensory neurons, which also responded to the
      TRPA1 agonist allyl isothiocyanate and the TRPV1 agonist capsaicin. 9-OA-NO(2)
      failed to activate neurons derived from TRPA1(-/-) mice. The action of 9-OA-NO(2)
      at nociceptive nerve terminals was investigated using an ex vivo extracellular
      recording preparation of individual bronchopulmonary C fibers in the mouse. 9-OA
      NO(2) evoked robust action potential discharge from capsaicin-sensitive fibers
      with slow conduction velocities (0.4-0.7 m/s), which was inhibited by the TRPA1
      antagonist AP-18. These data demonstrate that nitrooleic acid, a product of
      nitrative stress, can induce substantial nociceptive nerve activation through the
      selective and direct activation of TRPA1 channels.

PMID- 19171675
TI  - Dual mechanisms of CYP3A protein regulation by proinflammatory cytokine
      stimulation in primary hepatocyte cultures.
AB  - Whereas many cytochrome P450 enzymes are transcriptionally suppressed by
      inflammatory stimuli, down-regulation of CYP2B protein by the inflammatory
      cytokine interleukin (IL)-1beta is nitric oxide (NO)-dependent and occurs via
      polyubiquitination and proteasomal degradation. Here, we used iTRAQ proteomic
      analysis to search for other proteins that are potentially down-regulated by
      cellular NO in cultured rat hepatocytes, and we identified CYP3A1 as one such
      protein. Therefore, we examined whether CYP3A proteins, like CYP2B, undergo NO-
      and proteasome-dependent degradation in response to cytokine treatment of rat
      hepatocytes. In cultured rat hepatocytes treated with phenobarbital, IL-1beta
      stimulation failed to down-regulate CYP3A1 mRNA within 24 h of treatment, whereas
      CYP3A protein was down-regulated to 40% of control within 6 h, showing the post
      transcriptional down-regulation of CYP3A1 protein. The down-regulation of CYP3A
      after 9 h of stimulation by IL-1beta was attenuated by inhibitors of NO synthase
      (NOS) and of the proteasome, showing NO- and proteasome-dependent down-regulation
      at earlier time points. However, the down-regulation of CYP3A evoked by IL-1beta
      measured 24 h after stimulation was not affected by the inhibition of NOS or by
      proteasomal inhibitors, showing that CYP3A1 down-regulation at later time points
      is NO- and proteasome-independent. IL-6, which did not evoke NO production nor
      affect CYP3A1 mRNA within 24 h, produced a delayed proteasome-independent down
      regulation as well. Taken together, these observations show a novel dual mode of
      post-transcriptional CYP3A down-regulation by cytokines: NO- and proteasome
      dependent at earlier time points and NO- and proteasome-independent at later
      times.

PMID- 19171676
TI  - Expression and localization of cytosolic sulfotransferase (SULT) 1A1 and SULT1A3
      in normal human brain.
AB  - Cytosolic sulfotransferases (SULTs) are a family of Phase II drug-metabolizing
      enzymes that catalyze the transfer of a sulfonate group from 3'-phosphoadenosine
      5'-phosphosulfate to endogenous and xenobiotic compounds. Several SULT isoform
      messages have been detected in the human brain; however, protein expression
      patterns have not been characterized. Immunoblot analysis of the SULT1A1 and 1A3
      isoforms was carried out with cytosolic fractions isolated from superior temporal
      gyrus, hippocampus, cerebellum, occipital pole, frontal pole, and temporal pole
      regions of normal adult human brains. SULT1A1 expression was highest in cytosolic
      fractions isolated from cerebellum, occipital, and frontal lobes, whereas,
      SULT1A3 expression was highest in cytosol from superior temporal gyrus,
      hippocampus, and temporal lobe. SULT1A1 and SULT1A3 immunoreactivities were found
      in both neurons and glial cells by immunohistochemical analysis in all brain
      regions studied. SULT1A1 is known to catalyze the metabolism of small phenols,
      whereas SULT1A3 sulfates catecholamine neurotransmitters. Because SULT1A1 and 1A3
      have distinct substrate specificities, the differences in expression pattern and
      cellular localization of the SULT1A isoforms are probably associated with the
      distribution and function of their selective substrates in the different brain
      regions.

PMID- 19171677
TI  - Electrocatalytic drug metabolism by CYP2C9 bonded to a self-assembled monolayer
      modified electrode.
AB  - Cytochrome P450 (P450) enzymes typically require the presence of at least
      cytochrome P450 reductase (CPR) and NADPH to carry out the metabolism of
      xenobiotics. To address whether the need for redox transfer proteins and the
      NADPH cofactor protein could be obviated, CYP2C9 was bonded to a gold electrode
      through an 11-mercaptoundecanoic acid and octanethiol self-assembled monolayer
      (SAM) through which a current could be applied. Cyclic voltammetry demonstrated
      direct electrochemistry of the CYP2C9 enzyme bonded to the electrode and fast
      electron transfer between the heme iron and the gold electrode. To determine
      whether this system could metabolize warfarin analogous to microsomal or
      expressed enzyme systems containing CYP2C9, warfarin was incubated with the
      CYP2C9-SAM-gold electrode and a controlled potential was applied. The expected 7
      hydroxywarfarin metabolite was observed, analogous to expressed CYP2C9 systems,
      wherein this is the predominant metabolite. Current-concentration data generated
      with increasing concentrations of warfarin were used to determine the Michaelis
      Menten constant (K(m)) for the hydroxylation of warfarin (3 microM), which is in
      good agreement with previous literature regarding K(m) values for this reaction.
      In summary, the CYP2C9-SAM-gold electrode system was able to carry out the
      metabolism of warfarin only after application of an electrical potential, but in
      the absence of either CPR or NADPH. Furthermore, this system may provide a unique
      platform for both studying P450 enzyme electrochemistry and as a bioreactor to
      produce metabolites without the need for expensive redox transfer proteins and
      cofactors.

PMID- 19171678
TI  - A phosphomimetic mutation at threonine-57 abolishes transactivation activity and
      alters nuclear localization pattern of human pregnane x receptor.
AB  - The pregnane X receptor (PXR) plays crucial roles in multiple physiological
      processes. However, the signaling mechanisms responsible are not well defined; it
      is most likely that multiple functions of PXR are modulated by its
      phosphorylation. Therefore, we sought to determine whether mutation at a highly
      conserved Thr(57) affects human PXR (hPXR) function. Site-directed mutagenesis
      was performed to generate phosphorylation-deficient (hPXR(T57A)) and
      phosphomimetic (hPXR(T57D)) mutants. Gene reporter, Western blotting,
      immunocytochemistry, mammalian two-hybrid, and electrophoretic mobility shift
      assays were used to study cytochrome P450 3A4 (CYP3A4) promoter activation,
      protein levels, localization, cofactor interaction, and CYP3A4 promoter binding
      of the hPXR mutants, respectively. hPXR(T57D), but not hPXR(T57A), lost its
      transcriptional activity. Neither mutation altered hPXR's protein levels and
      interaction with steroid receptor coactivator-1. hPXR and hPXR(T57A) exhibited a
      homogenous nuclear distribution, whereas hPXR(T57D) exhibited a distinctive
      punctate nuclear localization pattern similar to that of hPXR mutants with
      impaired function that colocalize with silencing mediator of retinoid and thyroid
      receptors (SMRT), although silencing of SMRT did not rescue the altered function
      of hPXR(T57D). However, hPXR(T57D), but not hPXR(T57A), impaired hPXR's ability
      to bind to the CYP3A4 promoter, consistent with the mutant's transactivation
      function. Furthermore, the 70-kDa form of ribosomal protein S6 kinase (p70 S6K)
      phosphorylated hPXR in vitro and inhibited its transcriptional activity, whereas
      hPXR(T57A) partially resisted the inhibitory effect of p70 S6K. Our studies
      identify a functionally significant phosphomimetic mutant (hPXR(T57D)) and show
      p70 S6K phosphorylation and regulation of hPXR transactivation to support the
      notion that phosphorylation plays important roles in regulating hPXR function.

PMID- 19171679
TI  - Characterization of the disposition and toxicokinetics of N-butylpyridinium
      chloride in male F-344 rats and female B6C3F1 mice and its transport by organic
      cation transporter 2.
AB  - Studies were conducted to characterize the effect of dose and route of
      administration on the disposition of N-butylpyridinium chloride (NBuPy-Cl), an
      ionic liquid with solvent properties. Urine was the major route of NBuPy-Cl
      excretion after intravenous (5 mg/kg), single oral (0.5, 5, or 50 mg/kg), or
      repeated oral (50 mg/kg/day, 5 days) administration to male F-344 rats and single
      oral (50 mg/kg) administration to female B6C3F1 mice. Depending on the vehicle,
      absorption after dermal application (5 mg/kg, 125 microg/cm(2)) was 10 to 35% at
      96 h. After the single intravenous dose, the blood concentration of NBuPy-Cl
      decreased in a biphasic manner with an elimination half-life of 2.2 h and a
      clearance of 7 ml/min. After single oral administration of NBuPy-Cl (50 mg/kg),
      maximum blood concentration was reached at 1.3 h, and the bioavailability was
      determined to be 47% at 6 h based on the blood toxicokinetics and 67% at 72 h
      based on urinary excretion. In all the urine and blood samples, only the parent
      compound was detected. Coadministration of NBuPy-Cl and inulin (by intravenous
      injection) revealed that the clearance of NBuPy-Cl exceeded the rat glomerular
      filtration rate. After incubation with Chinese hamster ovary cells expressing
      human organic cation transporter 2 (hOCT2), NBuPy-Cl was transported effectively
      (K(t) = 18 microM), and also a potent inhibitor of hOCT2 mediated
      tetraethylammonium transport (IC(50) = 2.3 microM). In summary, NBuPy-Cl is
      partially absorbed from the gastrointestinal tract and eliminated rapidly in the
      urine as parent compound most likely by renal glomerular filtration and OCT2
      mediated secretion.

PMID- 19171680
TI  - Using a field quantitative real-time PCR test to rapidly identify highly viremic
      rift valley fever cases.
AB  - Approximately 8% of Rift Valley fever (RVF) cases develop severe disease, leading
      to hemorrhage, hepatitis, and/or encephalitis and resulting in up to 50% of
      deaths. A major obstacle in the management of RVF and other viral hemorrhagic
      fever cases in outbreaks that occur in rural settings is the inability to rapidly
      identify such cases, with poor prognosis early enough to allow for more
      aggressive therapies. During an RVF outbreak in Kenya in 2006 to 2007, we
      evaluated whether quantitative real-time reverse transcription-PCR (qRT-PCR)
      could be used in the field to rapidly identify viremic RVF cases with risk of
      death. In 52 of 430 RVF cases analyzed by qRT-PCR and virus culture, 18 died
      (case fatality rate [CFR] = 34.6%). Levels of viremia in fatal cases were
      significantly higher than those in nonfatal cases (mean of 10(5.2) versus 10(2.9)
      per ml; P < 0.005). A negative correlation between the levels of infectious virus
      particles and the qRT-PCR crossover threshold (C(T)) values allowed the use of
      qRT-PCR to assess prognosis. The CFR was 50.0% among cases with C(T) values of
      <27.0 (corresponding to 2.1 x 10(4) viral RNA particles/ml of serum) and 4.5%
      among cases with C(T) values of >or=27.0. This cutoff yielded 93.8% sensitivity
      and a 95.5% negative predictive value; the specificity and positive predictive
      value were 58% and 50%, respectively. This study shows a correlation between high
      viremia and fatality and indicates that qRT-PCR testing can identify nearly all
      fatal RVF cases.

PMID- 19171681
TI  - Mucor circinelloides as a cause of invasive maxillofacial zygomycosis: an
      emerging dimorphic pathogen with reduced susceptibility to posaconazole.
AB  - A case of maxillofacial zygomycosis caused by Mucor circinelloides, identified by
      phenotypic and molecular methods and treated successfully with liposomal
      amphotericin B (AmBisome) and surgical debridement, is described. The isolate was
      resistant to posaconazole. This report underscores the importance of prior
      susceptibility testing of zygomycetes to guide therapy with the most effective
      antifungal agent for an improved prognosis.

PMID- 19171682
TI  - Comparison of the roll plate method to the sonication method to diagnose catheter
      colonization and bacteremia in patients with long-term tunnelled catheters: a
      randomized prospective study.
AB  - Diagnosing catheter-related bloodstream infection (CRBSI) still often involves
      tip culture. The conventional method is the semiquantitative roll plate method.
      However, the use of a quantitative sonication technique could have additional
      value, as it may detect endoluminal microorganisms more easily. Because
      endoluminal infection tends to occur in long-term central venous catheters, we
      compared both techniques for patients with long-term tunnelled catheters. For 313
      consecutive Hickman catheter tips from 279 hematological patients, colonization
      detection rates were compared by performing both techniques in a random order,
      using conventional detection cutoffs. Additionally, for the subgroup of patients
      with clinical suspicion of CRBSI (n = 89), the diagnostic values of both
      techniques were compared. The overall tip colonization rate was 25%. For each
      technique, the detection rate tended to be better if that technique was performed
      first. The diagnostic performance for the subgroup of patients with clinical
      suspicion of CRBSI was limited and not different for both methods. Sensitivity
      and specificity were 45% and 84%, respectively, for sonication versus 35% and
      90%, respectively, for the roll plate technique. The fact that 35 of 40 patients
      with CRBSI received antimicrobial therapy before catheter removal and tip
      culture, in an attempt to salvage the catheter, may partly explain this poor
      performance. No differences were observed when catheters were stratified
      according to in situ time below or above the median of 4 weeks. The sonication
      culture technique was not better than the roll plate method to diagnose tip
      colonization or CRBSI in patients with long-term tunnelled catheters.

PMID- 19171683
TI  - Human-to-human transmission of tuberculosis caused by Mycobacterium bovis in
      immunocompetent patients.
AB  - Human-to-human transmission of Mycobacterium bovis in two immunocompetent
      patients from the same family was confirmed by spoligotyping (pattern F35, which
      was only observed in cattle from the same area in France). A single allelic
      difference between animal and human isolates was observed with mycobacterial
      interspersed repetitive units containing variable-number tandem repeats,
      suggesting a jump across the species barrier.

PMID- 19171684
TI  - Use of sloppy molecular beacon probes for identification of mycobacterial
      species.
AB  - We report here the use of novel "sloppy" molecular beacon probes in homogeneous
      PCR screening assays in which thermal denaturation of the resulting probe
      amplicon hybrids provides a characteristic set of amplicon melting temperature
      (T(m)) values that identify which species is present in a sample. Sloppy
      molecular beacons possess relatively long probe sequences, enabling them to form
      hybrids with amplicons from many different species despite the presence of
      mismatched base pairs. By using four sloppy molecular beacons, each possessing a
      different probe sequence and each labeled with a differently colored fluorophore,
      four different T(m) values can be determined simultaneously. We tested this
      technique with 27 different species of mycobacteria and found that each species
      generates a unique, highly reproducible signature that is unaffected by the
      initial bacterial DNA concentration. Utilizing this general paradigm, screening
      assays can be designed for the identification of a wide range of species.

PMID- 19171685
TI  - Molecular diagnosis of polymicrobial sepsis.

PMID- 19171686
TI  - Impact of blood cultures drawn by phlebotomy on contamination rates and health
      care costs in a hospital emergency department.
AB  - We conducted a prospective comparison of blood culture contamination rates
      associated with dedicated phlebotomists and nonphlebotomy staff in the emergency
      department (ED) at Parkland Memorial Hospital in Dallas, TX. In addition,
      hospital charges and lengths of stay were determined for patients with negative,
      false-positive, and true-positive blood culture results. A total of 5,432 blood
      culture collections from two ED areas, the western wing of the ED (ED west) and
      the nonwestern wing of the ED (ED nonwest), were evaluated over a 13-month
      period. Phlebotomists drew 2,012 (55%) of the blood cultures in ED west while
      nonphlebotomy staff drew 1,650 (45%) in ED west and 1,770 (100%) in ED nonwest.
      The contamination rates of blood cultures collected by phlebotomists were
      significantly lower than those collected by nonphlebotomists in ED west (62/2,012
      [3.1%] versus 122/1,650 [7.4%]; P < 0.001). Similar results were observed when
      rates between phlebotomists in ED west and nonphlebotomy staff in ED nonwest were
      compared (62/2,012 [3.1%] versus 100/1,770 [5.6%]; P < 0.001). Comparison of
      median patient charges between negative and false-positive episodes ($18,752
      versus $27,472) showed $8,720 in additional charges per contamination event while
      the median length of stay increased marginally from 4 to 5 days. By utilizing
      phlebotomists to collect blood cultures in the ED, contamination rates were
      lowered to recommended levels, with projected reductions in patient charges of
      approximately $4.1 million per year.

PMID- 19171687
TI  - Unilateral multicystic dysplastic kidney: a meta-analysis of observational
      studies on the incidence, associated urinary tract malformations and the
      contralateral kidney.
AB  - BACKGROUND: Many papers are published on cohorts with unilateral multicystic
      dysplastic kidney (MCDK) patients, but show variable results as to the incidence
      of associated urinary tract abnormalities. The objective of this study was to
      describe the status of the urinary tract, including contralateral hypertrophy and
      malformations, in patients with unilateral MCDK based on a meta-analysis of the
      literature, taking into account the timing of diagnosis (pre- versus postnatal)
      as a possible source of bias. METHODS: A systematic review of the scientific
      literature in English was conducted using PubMed and Embase. A meta-analysis was
      performed with the studies that were identified using our reproducible search.
      RESULTS: Based on analysis of the data in 19 populations, the overall incidence
      of unilateral MCDK is 1 in 4300 with an increasing trend over the years. A total
      of 67 cohorts with over 3500 patients with unilateral MCDK were included in the
      meta-analysis. Fifty-nine percent of patients were male and the MCDKs were
      significantly more often found on the left side (53.1%). Associated anomalies in
      the solitary functioning kidney were found in 1 in 3 patients, mainly
      vesicoureteric reflux (VUR, in 19.7%). In patients with VUR, 40% have severe
      contralateral VUR, defined as grade III-V. Contralateral hypertrophy, present in
      77% of patients after a follow-up of at least 10 years, showed a trend to be less
      pronounced in patients with VUR. Timing of the diagnosis of MCDK did not
      essentially influence the results. CONCLUSIONS: These aggregate results provide
      insight into the incidence, demographic data and associated anomalies in patients
      with unilateral MCDK. One in three patients with unilateral MCDK show anomalies
      in the contralateral, solitary functioning kidney. However, studies into the long
      term consequences of these anomalies are scarce.

PMID- 19171688
TI  - Women with Alport syndrome: risks and rewards of kidney donation.

PMID- 19171689
TI  - Olmesartan improves left ventricular function in pressure-overload hypertrophied
      rat heart by blocking angiotensin II receptor with synergic effects of
      upregulation of angiotensin converting enzyme 2.
AB  - It is not clear how the blocking effect of angiotensin II receptors by olmesartan
      affects the functional recovery of pressure-overload hypertrophied heart.
      Hypertrophied heart was created by abdominal aortic banding above the celiac
      artery in Wistar rats at the age of eight weeks. Hypertrophied heart was excised
      and studied at 10 and 16 weeks after the operation (HT groups). For the last four
      weeks before the experiment, olmesartan (0.2 mg/kg per day) was administered
      subcutaneously by osmotic minipumps (Olm groups). Left ventricular function was
      measured by Langendorff perfusion. The levels of mRNA for angiotensin-converting
      enzyme (ACE), ACE2 and extracellular signal-regulated kinases (ERKs) in
      myocardium were analyzed by RT-PCR. Left ventricular systolic (+dP/dt(max), left
      ventricular systolic pressure) and diastolic functions (-dP/dt(max), tau) were
      impaired in HT groups, while in Olm groups they were significantly improved. The
      left ventricle to body weight (LV/BW) ratio increased significantly in HT groups,
      but in Olm groups the LV/BW ratio decreased significantly in comparison with HT
      groups. The ACE2 mRNA level was significantly higher in Olm groups as compared
      with HT groups. Plasma angiotensin II and the ERK mRNA level in HT groups
      increased significantly, but decreased in Olm groups in comparison with HT groups
      significantly. Olmesartan improved left ventricular function and hypertrophy
      through the increase of the ACE2 mRNA and decrease of both angiotensin II and ERK
      mRNA in pressure-overload rat heart.

PMID- 19171690
TI  - Hyperaldosteronism in pregnancy.
AB  - Aldosterone is a key regulator of electrolyte and water homeostasis and plays a
      central role in blood pressure regulation. Hormonal changes during pregnancy,
      among them increased progesterone and aldosterone production, lead to the
      required plasma volume expansion of the maternal body as an accommodation
      mechanism for fetus growth. This review discusses the regulation of aldosterone
      production by aldosterone synthase (CYP11B2); the impact on aldosterone secretion
      due to the presence of a chimeric gene originating from a crossover between
      CYP11B1 and CYP11B2 in glucocorticoid remediable aldosteronism (GRA) - the
      inherited form of hypertension; enhanced aldosterone production in aldosterone
      producing adenoma (APA); and idiopathic hyperaldosteronism (IHA). Features of
      hyperaldosteronism are also found in patients with apparent mineralocorticoid
      excess (AME), in which glucocorticoids exacerbate activation of the
      mineralocorticoid receptor (MR) because of a defect in the 11beta-hydroxysteroid
      dehydrogenase type 2 enzyme. Regulation of aldosterone production and tissue
      specific activation of the mineralocorticoid receptor are prerequisites for
      optimal control of body fluids and blood pressure during pregnancy and contribute
      largely to the wellbeing of the mother-to-be.

PMID- 19171691
TI  - Aldosterone and progression of kidney disease.
AB  - Experimental evidence indicates that aldosterone, besides its mineralcorticoid
      properties, directly contributes to accelerate renal damage through promotion of
      cell growth, fibrosis and inflammation. As a consequence, attenuation of growth
      promoting and fibroproliferative effects of aldosterone might contribute to slow
      progression of chronic renal injury. Preliminary clinical observations have
      documented that aldosterone blockers added to angiotensin-converting enzyme
      inhibitor- and/or angiotensin receptor blocker-based regimens exerted significant
      antiproteinuric effects in patients with diabetic and nondiabetic nephropathies.
      Further studies in larger cohorts are now required to definitively address the
      safety and efficacy of aldosterone antagonism in patients with chronic kidney
      diseases.

PMID- 19171692
TI  - Enteral nutrition practice recommendations.

PMID- 19171693
TI  - East meets West: Chinese and U.S. college students' views on formal and informal
      crime control.
AB  - Both formal and informal crime control are used to deter people from engaging in
      criminal behavior that is harmful to the well-being of society. Formal criminal
      justice control uses the law and official government agencies to promote
      compliance, whereas informal criminal justice control uses morals and social
      institutions to encourage people to be law abiding. This study examined survey
      data to determine the importance of each form of social control among Chinese and
      U.S. college students. Chinese students were more likely to view formal and
      informal crime control as important mechanisms. Furthermore, Chinese students
      ranked the blending of formal and informal crime control as being more important.

PMID- 19171694
TI  - Glucose control in korean immigrants with type 2 diabetes.
AB  - Despite the rising incidence of type 2 diabetes in Korean immigrants, little is
      known about glucose control in these individuals. This descriptive study examined
      factors influencing glucose control in Korean immigrants with type 2 diabetes.
      Participants were 143 Korean immigrants with type 2 diabetes who completed
      questionnaires, a finger stick blood test for glycosylated hemoglobin (HbA1c),
      and anthropometric measures. The mean HbA1c level was 7.6 % (SD = 1.5; range =
      5.6 to 12.5). Less than half of the participants (41.3%) met the American
      Diabetes Association's goal of less than 7%. After adjusting for demographic and
      health variables, family diet support, waist-to-hip ratio (WHR), the duration of
      diabetes, the number of diabetic medications, and age significantly influenced
      glucose control. Findings support the positive role of family involvement in
      diabetes management. Patients with long-standing diabetes, higher WHR, and more
      diabetic medications deserve special attention because they tend to have higher
      HbA1c levels.

PMID- 19171695
TI  - Rural nurse cultural self-efficacy and job satisfaction.
AB  - This article explores relationships between rural nurse cultural self-efficacy
      and job satisfaction using an online survey of 104 rural nurses in the Northwest.
      The authors found that self-efficacy was associated with personal
      characteristics: rural lifestyle and job satisfaction. Nurses who were older,
      experienced, and with urban backgrounds reported more efficacies when caring for
      people of different ethnic or racial backgrounds, preferences, and health
      conditions. Nurses with high cultural self-efficacy expressed intention to leave
      employment. Rural background nurses expressed the most job satisfaction. The
      authors conclude exposure to diversity may increase cultural self-efficacy.

PMID- 19171696
TI  - Magnesium supplements for menopausal hot flashes.

PMID- 19171697
TI  - Combining docetaxel with estramustine: back to the future?

PMID- 19171698
TI  - The transition from phase II to phase III studies.

PMID- 19171699
TI  - Hematologic toxicity and double autografting of stem cells after myeloablative
      activities of yttrium-90-ibritumomab tiuxetan.

PMID- 19171700
TI  - Another infusion of hope.

PMID- 19171701
TI  - Bisphosphonates and bone turnover in premenopausal women receiving adjuvant
      chemotherapy.

PMID- 19171702
TI  - Progress in defining and treating high-risk neuroblastoma: lessons from the bench
      and bedside.

PMID- 19171704
TI  - Oral lesion as the first manifestation of choriocarcinoma of the testicle.

PMID- 19171703
TI  - Faculty development to change the paradigm of communication skills teaching in
      oncology.

PMID- 19171705
TI  - Pseudo meigs' syndrome secondary to colorectal adenocarcinoma metastasis to the
      ovaries.

PMID- 19171706
TI  - Patient characteristics and prognosis in metastatic breast cancer.

PMID- 19171707
TI  - Safety of ovarian preservation in premenopausal women with endometrial cancer.
AB  - PURPOSE: Oophorectomy is commonly performed in premenopausal women with
      endometrial cancer who undergo hysterectomy. The benefits of oophorectomy in this
      setting are unknown, and the procedure subjects women to the long-term sequelae
      of estrogen deprivation. We examined the safety of ovarian preservation in young
      women with endometrial cancer who underwent hysterectomy. PATIENTS AND METHODS:
      Women < or = 45 years of age with stage I endometrial cancer recorded from 1988
      to 2004 in the Surveillance, Epidemiology, and End Results Database were
      examined. We developed Cox proportional hazards models and Kaplan-Meier curves to
      compare women who underwent oophorectomy with those who had ovarian preservation.
      RESULTS: A total of 3,269 women, including 402 patients (12%) who had ovarian
      preservation, were identified. Younger age (P < .0001), later year of diagnosis
      (P = .04), residence in the eastern United States (P = .02), and low tumor grade
      (P < .0001) were associated with ovarian preservation. In a multivariate Cox
      model, ovarian preservation had no effect on either cancer-specific (hazard ratio
      [HR] = 0.58; 95% CI, 0.14 to 2.44) or overall (HR = 0.68; 95% CI, 0.34 to 1.35)
      survival. The findings were unchanged when women who received pelvic radiotherapy
      were excluded. CONCLUSION: Ovarian preservation in premenopausal women with early
      stage endometrial cancer may be safe and not associated with an increase in
      cancer-related mortality.

PMID- 19171708
TI  - Randomized phase II trial of first-line treatment with sorafenib versus
      interferon Alfa-2a in patients with metastatic renal cell carcinoma.
AB  - PURPOSE: An open-label, phase II study to evaluate progression-free survival
      (PFS), overall best response, adverse events (AEs), and patient-reported outcomes
      with sorafenib versus interferon alfa-2a (IFN-alpha-2a) in patients with
      untreated, advanced renal cancer. PATIENTS AND METHODS: A total of 189 patients
      were randomly assigned to oral sorafenib 400 mg twice daily or to subcutaneous
      IFN-alpha-2a 9 million U three times weekly (period 1). Sorafenib patients who
      progressed were dose-escalated to 600 mg twice daily; IFN-alpha-2a patients who
      progressed were switched to sorafenib 400 mg twice daily (period 2). RESULTS: In
      period 1 PFS was similar for sorafenib-treated (n = 97; 5.7 months) and IFN-alpha
      2a-treated patients (n = 92; 5.6 months); more sorafenib-treated patients had
      tumor shrinkage (68.2% v 39.0%). Common drug-related AEs (Grades > or = 3) for
      sorafenib were hand-foot skin reaction (11.3%), diarrhea (6.2%), and
      rash/desquamation (6.2%); for IFN-alpha-2a, these were fatigue (10.0%), nausea
      (3.3%), flu-like syndrome (2.2%), and anorexia (2.2%). Sorafenib-treated patients
      reported fewer symptoms, better quality of life (QOL), and greater treatment
      satisfaction. In period 2, 41.9% of patients who received sorafenib 600 mg twice
      daily (n = 43) experienced tumor reduction (median PFS, 3.6 months). After the
      switch to sorafenib 400 mg twice daily, tumors were reduced in 76.2% of 50
      patients (median PFS, 5.3 months). AEs were mostly grade 1 to 2; no increase in
      AEs of grades > or = 3 occurred after sorafenib dose escalation. CONCLUSION: In
      this study, sorafenib resulted in similar PFS as IFN-alpha-2a in patients with
      untreated RCC. However, sorafenib-treated patients experienced greater rates of
      tumor size reduction, better QOL, and improved tolerability. Both dose escalation
      of sorafenib after progression and a switch to sorafenib after progression on IFN
      alpha-2a resulted in clinical benefit.

PMID- 19171709
TI  - Phase I trial of oral irinotecan and temozolomide for children with relapsed high
      risk neuroblastoma: a new approach to neuroblastoma therapy consortium study.
AB  - PURPOSE: Irinotecan and temozolomide have single-agent activity and schedule
      dependent synergy against neuroblastoma. Because protracted administration of
      intravenous irinotecan is costly and inconvenient, we sought to determine the
      maximum-tolerated dose (MTD) of oral irinotecan combined with temozolomide in
      children with recurrent/resistant high-risk neuroblastoma. PATIENTS AND METHODS:
      Patients received oral temozolomide on days 1 through 5 combined with oral
      irinotecan on days 1 through 5 and 8 through 12 in 3-week courses. Daily oral
      cefixime was used to reduce irinotecan-associated diarrhea. RESULTS: Fourteen
      assessable patients received 75 courses. Because neutropenia and thrombocytopenia
      were initially dose-limiting, temozolomide was reduced from 100 to 75 mg/m(2)/d
      for subsequent patients. Irinotecan was then escalated from 30 to 60 mg/m2/d.
      First-course grade 3 diarrhea was dose-limiting in one of six patients treated at
      the irinotecan MTD of 60 mg/m2/d. Other toxicities were mild and reversible. The
      median SN-38 lactone area under the plasma concentration versus time curve at
      this dose was 72 ng . hr/mL. One patient with bulky soft tissue disease had a
      complete response through six courses. Six additional patients received a median
      of seven courses (range, three to 22 courses) before progression. CONCLUSION:
      This all-oral regimen was feasible and well tolerated in heavily pretreated
      children with resistant neuroblastoma, and seven (50%) of 14 assessable patients
      had response or disease stabilization for three or more courses in this phase I
      trial. SN-38 lactone exposures were similar to those reported with protracted
      intravenous irinotecan. The dosages recommended for further study in this patient
      population are temozolomide 75 mg/m2/d plus irinotecan 60 mg/m2/d when given with
      cefixime.

PMID- 19171711
TI  - Excellent outcome with reduced treatment for infants with disseminated
      neuroblastoma without MYCN gene amplification.
AB  - PURPOSE: On the assumption that most infants with disseminated neuroblastoma
      without MYCN amplification (MYCNA) have a favorable prognosis, two concomitant
      prospective trials were started in which chemotherapy was limited to patients
      presenting life- or organ-threatening symptoms or overt metastases to skeleton,
      lung, or CNS. Surgery was to be performed only in the absence of surgical risk
      factors. PATIENTS AND METHODS: One hundred seventy infants with disseminated
      neuroblastoma without MYCNA, diagnosed between June 1999 and June 2004 in nine
      European countries were eligible for either of the two studies. Trial 99.2
      included all stage 4S infants and those with stage 4 with a primary tumor
      infiltrating across the midline or positive skeletal scintigraphy who were to be
      observed in absence of symptoms. Trial 99.3 included infants with overt
      metastases to the skeleton, lung, and CNS to be treated with a minimum of four
      chemotherapy courses. RESULTS: The 125 infants treated on trial 99.2 had a 2-year
      overall survival (OS) of 97.6% with no difference between asymptomatic and
      symptomatic patients (97.7% v 97.3%), patients without or with unresectable
      primary tumors (96.8% v 100%), and patients without or with positive skeletal
      scintigraphy without radiologic abnormalities (97.2% v 100%). The 45 infants
      treated on trial 99.3 had a 2-year OS of 95.6%. No patients died of surgery- or
      chemotherapy-related complications. CONCLUSION: Infants with disseminated disease
      without MYCNA have excellent survival with minimal or no treatment. Asymptomatic
      infants with an unresectable primary tumor or positive skeletal scintigraphy
      without radiologic abnormalities may undergo observation alone.

PMID- 19171710
TI  - Sensitivity of surveillance studies for detecting asymptomatic and unsuspected
      relapse of high-risk neuroblastoma.
AB  - PURPOSE: Relapse-free survival (RFS) is a powerful measure of treatment efficacy.
      We describe the sensitivity of standard surveillance studies for detecting
      relapse of neuroblastoma (NB). PATIENTS AND METHODS: The patients were in
      complete/very good partial remission of high-risk NB; routine monitoring revealed
      asymptomatic and, therefore, unsuspected relapses in 113 patients, whereas 41
      patients had symptoms prompting urgent evaluations. Assessments every 2 to 4
      months included computed tomography, iodine-131-metaiodobenzylguanidine (131)I
      MIBG; through November 1999) or iodine-123-metaiodobenzylguanidine ((123)I-MIBG)
      scan, urine catecholamines, and bone marrow (BM) histology. Bone scan was routine
      through 2002. RESULTS: (123)I-MIBG scan was the most reliable study for revealing
      unsuspected relapse; it had an 82% detection rate, which was superior to the
      rates with (131)I-MIBG scan (64%; P = .1), bone scan (36%; P < .001), and BM
      histology (34%; P < .001). Among asymptomatic patients, (123)I-MIBG scan was the
      sole positive study indicating relapse in 25 (27%) of 91 patients compared with
      one (4.5%) of 22 patients for (131)I-MIBG scan (P = .04) and 0% to 6% of patients
      for each of the other studies (P < .001). Patients whose monitoring included
      (123)I-MIBG scan were significantly less likely than patients monitored by (131)I
      MIBG scan to have an extensive osteomedullary relapse and had a significantly
      longer survival from relapse (P < .001) and from diagnosis (P = .002). They also
      had significantly longer survival than patients with symptomatic relapses (P =
      .002). CONCLUSION: (123)I-MIBG scan is essential for valid estimation of the
      duration of RFS of patients with high-risk NB. Without monitoring that includes
      (123)I-MIBG scan, caution should be used when comparing RFS between institutions
      and protocols.

PMID- 19171712
TI  - Phase I study of lapatinib in combination with chemoradiation in patients with
      locally advanced squamous cell carcinoma of the head and neck.
AB  - PURPOSE: This study (EGF100262) sought to establish the recommended phase II dose
      of lapatinib with chemoradiotherapy in patients with locally advanced squamous
      cell carcinoma of the head and neck (LA SCCHN). PATIENTS AND METHODS: Patients
      were enrolled onto cohorts of escalating lapatinib dose (500, 1,000, and 1,500
      mg/d). Patients received 1 week of lapatinib alone followed by 6.5 to 7 weeks of
      the same dose of lapatinib plus radiotherapy 66 to 70 Gy and cisplatin 100
      mg/m(2) on days 1, 22, and 43 of radiotherapy. End points included
      safety/tolerability and clinical activity. RESULTS: Thirty-one patients were
      enrolled (seven patients in each of the 500- and 1,000-mg cohorts and three in
      the 1,500-mg cohort; an additional 14 patients were enrolled at 1,500 mg in a
      safety cohort). Dose-limiting toxicities (DLTs) included perforated ulcer in one
      patient in the 500-mg cohort and transient elevation of liver enzymes in one
      patient in the 1,000-mg cohort. No DLTs were observed in the 1,500-mg cohort.
      Therefore, the recommended phase II dose was defined as lapatinib 1,500 mg/d with
      chemoradiotherapy. The most common grade 3 to 4 adverse events were radiation
      mucositis, radiation dermatitis, lymphopenia, and neutropenia. No patients
      experienced drug-related symptomatic cardiotoxicity, and no interstitial
      pneumonitis was reported. The overall response rate was 81% (65% at the
      recommended phase II dose). CONCLUSION: The recommended phase II dose is
      lapatinib 1,500 mg/d with chemoradiotherapy in patients with LA SCCHN; this
      regimen is associated with an acceptable tolerability profile. Given these
      findings, randomized phase II and III studies of lapatinib plus chemoradiotherapy
      have been initiated.

PMID- 19171713
TI  - Overall genomic pattern is a predictor of outcome in neuroblastoma.
AB  - PURPOSE: For a comprehensive overview of the genetic alterations of
      neuroblastoma, their association and clinical significance, we conducted a whole
      genome DNA copy number analysis. PATIENTS AND METHODS: A series of 493
      neuroblastoma (NB) samples was investigated by array-based comparative genomic
      hybridization in two consecutive steps (224, then 269 patients). RESULTS: Genomic
      analysis identified several types of profiles. Tumors presenting exclusively
      whole-chromosome copy number variations were associated with excellent survival.
      No disease-related death was observed in this group. In contrast, tumors with any
      type of segmental chromosome alterations characterized patients with a high risk
      of relapse. Patients with both numerical and segmental abnormalities clearly
      shared the higher risk of relapse of segmental-only patients. In a multivariate
      analysis, taking into account the genomic profile, but also previously described
      individual genetic and clinical markers with prognostic significance, the
      presence of segmental alterations with (HR, 7.3; 95% CI, 3.7 to 14.5; P < .001)
      or without MYCN amplification (HR, 4.5; 95% CI, 2.4 to 8.4; P < .001) was the
      strongest predictor of relapse; the other significant variables were age older
      than 18 months (HR, 1.8; 95% CI, 1.2 to 2.8; P = .004) and stage 4 (HR, 1.8; 95%
      CI, 1.2 to 2.7; P = .005). Finally, within tumors showing segmental alterations,
      stage 4, age, MYCN amplification, 1p and 11q deletions, and 1q gain were
      independent predictors of decreased overall survival. CONCLUSION: The analysis of
      the overall genomic pattern, which probably unravels particular genomic
      instability mechanisms rather than the analysis of individual markers, is
      essential to predict relapse in NB patients. It adds critical prognostic
      information to conventional markers and should be included in future treatment
      stratification.

PMID- 19171714
TI  - Iodine-131--metaiodobenzylguanidine double infusion with autologous stem-cell
      rescue for neuroblastoma: a new approaches to neuroblastoma therapy phase I
      study.
AB  - PURPOSE: Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) provides targeted
      radiotherapy with more than 30% response rate in refractory neuroblastoma, but
      activity infused is limited by radiation safety and hematologic toxicity. The
      goal was to determine the maximum-tolerated dose of (131)I-MIBG in two
      consecutive infusions at a 2-week interval, supported by autologous stem-cell
      rescue (ASCR) 2 weeks after the second dose. PATIENTS AND METHODS: The (131)I
      MIBG dose was escalated using a 3 + 3 phase I trial design, with levels
      calculated by cumulative red marrow radiation index (RMI) from both infusions.
      Using dosimetry, the second infusion was adjusted to achieve the target RMI,
      except at level 4, where the second infusion was capped at 21 mCi/kg. RESULTS:
      Twenty-one patients were enrolled onto the study at levels 1 to 4, with 18
      patients assessable for toxicity and 20 patients assessable for response.
      Cumulative (131)I-MIBG given to achieve the target RMI ranged from 22 to 50
      mCi/kg, with cumulative RMI of 3.2 to 8.92 Gy. No patient had a dose-limiting
      toxicity. Reversible grade 3 nonhematologic toxicity occurred in six patients at
      level 4, establishing the recommended cumulative dose as 36 mCi/kg. The median
      time to absolute neutrophil count more than 500/microL after ASCR was 13 days (4
      to 27 days) and to platelet independence was 17 days (6 to 47 days). Responses
      included two partial responses, eight mixed responses, three stable disease, and
      seven progressive disease. Responses by semiquantitative MIBG score occurred in
      eight patients, soft tissue responses occurred in five of 11 patients, but bone
      marrow responses occurred in only two of 13 patients. CONCLUSION: The lack of
      toxicity with this approach allowed dramatic dose intensification of (131)I-MIBG,
      with minimal toxicity and promising activity.

PMID- 19171715
TI  - Poor survival for infants with MYCN-amplified metastatic neuroblastoma despite
      intensified treatment: the International Society of Paediatric Oncology European
      Neuroblastoma Experience.
AB  - PURPOSE: To report the results of a prospective, nonrandomized European study on
      infants with neuroblastoma and MYCN gene amplification. PATIENTS AND METHODS:
      Infants with neuroblastoma (stage 2, 3, 4, and 4s) and MYCN gene amplification
      who were diagnosed between 1999 and 2004 were eligible for enrollment onto the
      study. After diagnosis, staging, and mandatory biologic studies, induction
      chemotherapy (IC) with conventional drugs was administered, followed by delayed
      surgery, megatherapy (busulfan-melphalan as a conditioning regimen), and local
      radiotherapy. RESULTS: Of the 46 infants enrolled onto the study, 35 infants were
      eligible; of these 35 infants, 97% had metastatic spread (24 infants had stage 4,
      and 10 infants had stage 4s). Two-year overall survival (OS) was 30% (SE, 0.08),
      with median survival time of 12 months, and 23 deaths due to disease. Two-year,
      event-free survival (EFS) was 29% (SE, 0.07). The treatment was well tolerated
      with no deaths as a result of toxicity or severe toxicity. Despite protocol
      adherence, 30% of the patients who were assessable for response to IC experienced
      disease progression or did not respond. Stage and high lactate dehydrogenase
      reached significance in the univariate analysis (P = .028 and .039, respectively
      for OS; and P = .05 and .031 respectively, for EFS). Ten of 16 patients who
      received megatherapy are still alive. CONCLUSION: Although treatment was well
      tolerated, survival was poor and our IC failed to achieve a satisfactory response
      in 30% of our patients. New therapeutic approaches and more intense world-wide
      collaboration are needed to achieve a cure in this population.

PMID- 19171716
TI  - Long-term results for children with high-risk neuroblastoma treated on a
      randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a
      children's oncology group study.
AB  - PURPOSE We assessed the long-term outcome of patients enrolled on CCG-3891, a
      high-risk neuroblastoma study in which patients were randomly assigned to undergo
      autologous purged bone marrow transplantation (ABMT) or to receive chemotherapy,
      and subsequent treatment with 13-cis-retinoic acid (cis-RA). PATIENTS AND METHODS
      Patients received the same induction chemotherapy, with random assignment (N =
      379) to consolidation with myeloablative chemotherapy, total-body irradiation,
      and ABMT versus three cycles of intensive chemotherapy. Patients who completed
      consolidation without disease progression were randomly assigned to receive no
      further therapy or cis-RA for 6 months. Results The event-free survival (EFS) for
      patients randomly assigned to ABMT was significantly higher than those randomly
      assigned to chemotherapy; the 5-year EFS (mean +/- SE) was 30% +/- 4% versus 19%
      +/- 3%, respectively (P = .04). The 5-year EFS (42% +/- 5% v 31% +/- 5%) from the
      time of second random assignment was higher for cis-RA than for no further
      therapy, though it was not significant. Overall survival (OS) was significantly
      higher for each random assignment by a test of the log(-log(.)) transformation of
      the survival estimates at 5 years (P < .01). The 5-year OS from the second random
      assignment of patients who underwent both random assignments and who were
      assigned to ABMT/cis-RA was 59% +/- 8%; for ABMT/no cis-RA, it was 41% +/- 8%
      [corrected]; for continuing chemotherapy/cis-RA, it was 38% +/- 7%; and for
      chemotherapy/no cis-RA, it was 36% +/- 7%. CONCLUSION: Myeloablative therapy and
      autologous hematopoietic cell rescue result in significantly better 5-year EFS
      than nonmyeloablative chemo therapy; neither myeloablative therapy with
      [corrected] autologous hematopoietic cell rescue nor cis-RA given after
      consolidation therapy significantly improved OS.

PMID- 19171717
TI  - Effect of progression from impaired glucose tolerance to diabetes on
      cardiovascular risk factors and its amelioration by lifestyle and metformin
      intervention: the Diabetes Prevention Program randomized trial by the Diabetes
      Prevention Program Research Group.
AB  - OBJECTIVE: Although subjects with diabetes have increased risk for cardiovascular
      disease (CVD), the evolution of this increased risk as pre-diabetic individuals
      progress to diabetes is not understood. This study examines the longitudinal
      relationship between selected CVD risk factors (blood pressure, triglycerides,
      HDL and LDL cholesterol, and LDL peak particle density [PPD]) and glycemia in the
      three treatment groups of the Diabetes Prevention Program. RESEARCH DESIGN AND
      METHODS: A total of 3,234 participants with impaired glucose tolerance (IGT) were
      followed for a mean of 3.2 years after randomization to intensive lifestyle
      intervention (ILS), metformin, or placebo. Using repeated-measures models,
      adjusted mean levels of risk factors were estimated for an annual change in
      glycemic status. Tests were also conducted to assess the risk factor trends with
      improvement or worsening of glycemic status. RESULTS: CVD risk factor values and
      changes from baseline became more unfavorable as glucose tolerance status
      deteriorated but improved with reversion to normal glucose tolerance (NGT),
      especially in the ILS intervention group (trend test P < 0.001 for all risk
      factors except for LDL PPD [P = 0.02] in ILS and HDL cholesterol [P = 0.02] in
      placebo). Although there were few significant differences in the transition from
      IGT to diabetes, there were strong relationships between risk factors and
      continuous measures of glycemia. CONCLUSIONS: Progression from IGT to diabetes is
      associated with mild deterioration, whereas reversion to NGT is associated with
      improvement in risk factors. Early intervention with ILS, but less so with
      metformin, in participants at high risk for diabetes improves the cardiovascular
      risk and glucose tolerance profile simultaneously.

PMID- 19171718
TI  - Prospective study of zinc intake and risk of type 2 diabetes in women.
AB  - OBJECTIVE: The aim of this study is to investigate the intake of zinc in relation
      to risk of type 2 diabetes in U.S. women. RESEARCH DESIGN AND METHODS: Dietary
      intakes of zinc and other nutrients were assessed and updated using a validated
      food frequency questionnaire from 1980 to 2002 among 82,297 women who were aged
      33-60 years at baseline in 1980 and followed up to 2004 in the Nurses' Health
      Study. RESULTS: During the 24 years of follow-up, 6,030 incident cases of type 2
      diabetes were ascertained. After adjustment of lifestyle and dietary risk
      factors, the relative risks (RRs) (95% CI) of type 2 diabetes comparing the
      highest with the lowest quintiles were 0.90 (0.82-0.99) (P(trend) = 0.04) for
      total zinc intake and 0.92 (0.84-1.00) (P(trend) = 0.009) for dietary zinc intake
      from food sources, respectively. We further found an inverse association for
      dietary zinc to heme iron ratio. After multivariate adjustment of covariates, the
      RRs (95% CI) across quintiles of this ratio were 1.0 (reference), 0.93 (0.86
      1.01), 0.86 (0.79-0.94), 0.82 (0.75-0.90), and 0.72 (0.66-0.80), respectively
      (P(trend) < 0.0001). CONCLUSIONS: Higher zinc intake may be associated with a
      slightly lower risk of type 2 diabetes in women. More studies are warranted to
      confirm this association and to explore potential mechanisms.

PMID- 19171719
TI  - Prevalence and correlates of depression in individuals with and without type 1
      diabetes.
AB  - OBJECTIVE: Depression is associated with poor glycemic control and complications
      in people with type 1 diabetes. We assessed the prevalence of depression and
      antidepressant medication use among adults with and without type 1 diabetes and
      the association between depression and diabetes complications. RESEARCH DESIGN
      AND METHODS: In 2006-2008, the Coronary Artery Calcification in Type 1 Diabetes
      Study applied the Beck Depression Inventory II (BDI-II) to 458 participants with
      type 1 diabetes (47% male, aged 44 +/- 9 years, type 1 diabetes duration 29 +/- 9
      years) and 546 participants without diabetes (nondiabetic group) (51% male, aged
      47 +/- 9 years). Use of antidepressant medication was self-reported. Depression
      was defined as a BDI-II score >14 and/or use of antidepressant medication.
      Occurrence of diabetes complications (retinopathy, blindness, neuropathy,
      diabetes-related amputation, and kidney or pancreas transplantation) was self
      reported. RESULTS: Mean BDI-II score, adjusted for age and sex, was significantly
      higher in participants with type 1 diabetes than in nondiabetic participants
      (least-squares mean +/- SE: 7.4 +/- 0.3 vs. 5.0 +/- 0.3; P < 0.0001). Type 1
      diabetic participants reported using more antidepressant medications (20.7 vs.
      12.1%, P = 0.0003). More type 1 diabetic than nondiabetic participants were
      classified as depressed by BDI-II cut score (17.5 vs. 5.7%, P < 0.0001) or by
      either BDI-II cut score or antidepressant use (32.1 vs. 16.0%, P < 0.0001).
      Participants reporting diabetes complications (n = 209) had higher mean BDI-II
      scores than those without complications (10.7 +/- 9.3 vs. 6.4 +/- 6.3, P <
      0.0001). CONCLUSIONS: Compared with nondiabetic participants, adults with type 1
      diabetes report more symptoms of depression and more antidepressant medication
      usage. Depression is highly prevalent in type 1 diabetes and requires further
      study on assessment and treatment.

PMID- 19171720
TI  - Cost-effectiveness of surgically induced weight loss for the management of type 2
      diabetes: modeled lifetime analysis.
AB  - OBJECTIVE: To estimate the cost-effectiveness of surgically induced weight loss
      relative to conventional therapy for the management of recently diagnosed type 2
      diabetes in class I/II obese patients. RESEARCH DESIGN AND METHODS: This study
      builds on a within-trial cost-efficacy analysis. The analysis compares the
      lifetime costs and quality-adjusted life-years (QALYs) between the two
      intervention groups. Intervention costs were extrapolated based on observed
      resource utilization during the trial. The proportion of patients in each
      intervention group with remission of diabetes at 2 years was the same as that
      observed in the trial. Health care costs for patients with type 2 diabetes and
      outcome variables required to derive estimates of QALYs were sourced from
      published literature. A health care system perspective was adopted. Costs and
      outcomes were discounted annually at 3%. Costs are presented in 2006 Australian
      dollars (AUD) (currency exchange: 1 AUD = 0.74 USD). RESULTS: The mean number of
      years in diabetes remission over a lifetime was 11.4 for surgical therapy
      patients and 2.1 for conventional therapy patients. Over the remainder of their
      lifetime, surgical and conventional therapy patients lived 15.7 and 14.5
      discounted QALYs, respectively. The mean discounted lifetime costs were 98,900
      AUD per surgical therapy patient and 101,400 AUD per conventional therapy
      patient. Relative to conventional therapy, surgically induced weight loss was
      associated with a mean health care saving of 2,400 AUD and 1.2 additional QALYs
      per patient. CONCLUSIONS: Surgically induced weight loss is a dominant
      intervention (it both saves health care costs and generates health benefits) for
      managing recently diagnosed type 2 diabetes in class I/II obese patients in
      Australia.

PMID- 19171721
TI  - Prevalence of abnormal lipid profiles and the relationship with the development
      of microalbuminuria in adolescents with type 1 diabetes.
AB  - OBJECTIVE: To explore the prevalence of lipid abnormalities and their
      relationship with albumin excretion and microalbuminuria in adolescents with type
      1 diabetes. RESEARCH DESIGN AND METHODS: The study population comprised 895 young
      subjects with type 1 diabetes (490 males); median age at the baseline assessment
      was 14.5 years (range 10-21.1), and median diabetes duration was 4.8 years (0.2
      17). A total of 2,194 nonfasting blood samples were collected longitudinally for
      determination of total cholesterol, LDL cholesterol, HDL cholesterol, TG, and non
      HDL cholesterol. Additional annually collected data on anthropometric parameters,
      A1C, and albumin-to-creatinine ratio (ACR) were available. RESULTS: Total
      cholesterol, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol were
      higher in females than in males (all P < 0.001). A significant proportion of
      subjects presented sustained lipid abnormalities during follow-up: total
      cholesterol >5.2 mmol/l (18.6%), non-HDL cholesterol >3.4 mmol/l (25.9%), TG >1.7
      mmol/l (20.1%), and LDL cholesterol >3.4 mmol/l (9.6%). Age and duration were
      significantly related to all lipid parameters (P < 0.001); A1C was independently
      related to all parameters (P < 0.001) except HDL cholesterol, whereas BMI SD
      scores were related to all parameters (P < 0.05) except total cholesterol. Total
      cholesterol and non-HDL cholesterol were independently related to longitudinal
      changes in ACR (B coefficient +/- SE): 0.03 +/- 0.01/1 mmol/l, P = 0.009, and
      0.32 +/- 0.014/1 mmol/l, P = 0.02, respectively. Overall mean total cholesterol
      and non-HDL cholesterol were higher in microalbuminuria positive (n = 115) than
      in normoalbuminuric subjects (n = 780): total cholesterol 4.7 +/- 1.2 vs. 4.5 +/-
      0.8 mmol/l (P = 0.04) and non-HDL cholesterol 3.2 +/- 1.2 vs. 2.9 +/- 0.8 mmol/l
      (P = 0.03). CONCLUSIONS: In this longitudinal study of adolescents with type 1
      diabetes, sustained lipid abnormalities were related to age, duration, BMI, and
      A1C. Furthermore, ACR was related to both total cholesterol and non-HDL
      cholesterol, indicating a potential role in the pathogenesis of diabetic
      nephropathy.

PMID- 19171722
TI  - Is femur length the key height component in risk prediction of type 2 diabetes
      among adults?
AB  - OBJECTIVE: To examine the diabetes risk association with femur length, standing
      height, and height without femur length (HWFL) (HWFL = standing height--femur
      length). RESEARCH DESIGN AND METHODS: We used data from three time periods of the
      National Health and Nutrition Examination Survey (1999-2000, 2001-2002, and 2003
      2004) for this cross-sectional analysis and confined the eligible subjects to
      6,188 adults aged 20+ years who had fasted >or=8 h and had no missing values of
      femur length or standing height. The outcome measure was type 2 diabetes.
      RESULTS: Multivariate logistic regression analyses indicated that the odds of
      type 2 diabetes per 1-SD value increase in femur length, standing height, and
      HWFL were 0.73 (95% CI 0.61-0.86), 0.91 (0.75-1.10), and 1.09 (0.90-1.32) for
      men, respectively, and 0.82 (0.70-0.97), 0.99 (0.82-1.21), and 1.11 (0.93-1.33)
      for women. CONCLUSIONS: Our study supports the hypothesis that femur length may
      be the key height component in diabetes risk association.

PMID- 19171723
TI  - Simulated physician learning intervention to improve safety and quality of
      diabetes care: a randomized trial.
AB  - OBJECTIVE: To assess two physician learning interventions designed to improve
      safety and quality of diabetes care delivered by primary care physicians (PCPs).
      RESEARCH DESIGN AND METHODS: This group randomized clinical trial included 57
      consenting PCPs and their 2,020 eligible adult patients with diabetes. Physicians
      were randomized to no intervention (group A), a simulated case-based physician
      learning intervention (group B), or the same simulated case-based learning
      intervention with physician opinion leader feedback (group C). Dependent
      variables included A1C values, LDL cholesterol values, pharmacotherapy
      intensification rates in patients not at clinical goals, and risky prescribing
      events. RESULTS: Groups B and C had substantial reductions in risky prescribing
      of metformin in patients with renal impairment (P = 0.03). Compared with groups A
      and C, physicians in group B achieved slightly better glycemic control (P =
      0.04), but physician intensification of oral glucose-lowering medications was not
      affected by interventions (P = 0.41). Lipid management improved over time (P <
      0.001) but did not differ across study groups (P = 0.67). CONCLUSIONS: A
      simulated, case-based learning intervention for physicians significantly reduced
      risky prescribing events and marginally improved glycemic control in actual
      patients. The addition of opinion leader feedback did not improve the learning
      intervention. Refinement and further development of this approach is warranted.

PMID- 19171724
TI  - Increased persistency in medication use by U.S. Medicare beneficiaries with
      diabetes is associated with lower hospitalization rates and cost savings.
AB  - OBJECTIVE: To assess the relationship between annual fills for antidiabetes
      medications, ACE inhibitors, angiotensin II receptor blockers (ARBs), and lipid
      lowering agents on hospitalization and Medicare spending for beneficiaries with
      diabetes. RESEARCH DESIGN AND METHODS: Using Medicare Current Beneficiary Survey
      data from 1997 to 2004, we identified 7,441 community-dwelling beneficiaries with
      diabetes, who contributed 14,317 person-years of data for the analysis. We used
      multivariate regression analysis to estimate the effect of persistency in
      medication fills on hospitalization risk, hospital days, and Medicare spending.
      RESULTS: For users of older oral antidiabetes agents, ACE inhibitors, ARBs, and
      statins, each additional prescription fill was associated with significantly
      lower risk of hospitalization, fewer hospital days, and lower Medicare spending.
      CONCLUSIONS: These results suggest an economic case for promoting greater
      persistency in use of drugs with approved indications by Medicare beneficiaries
      with diabetes; however, additional research is needed to corroborate the study's
      cross-sectional findings.

PMID- 19171725
TI  - Effect of intensive glycemic control and diabetes complications on lower urinary
      tract symptoms in men with type 1 diabetes: Diabetes Control and Complications
      Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.
AB  - OBJECTIVE: Although diabetes is known to result in lower urinary tract symptoms
      (LUTS) in men, it remains unclear if glycemic control can mitigate urinary
      symptoms. We studied how diabetic characteristics are related to LUTS in the men
      who completed the urological assessment component (UroEDIC) of the Epidemiology
      of Diabetes Interventions and Complications (EDIC) follow-up study of the
      Diabetes Control and Complications Trial (DCCT) participants. RESEARCH DESIGN AND
      METHODS: Study participants were men who completed the UroEDIC questionnaire at
      the year 10 DCCT/EDIC follow-up examination, which included data on genitourinary
      tract function and the American Urological Association Symptom Index (AUASI).
      Analyses were conducted to assess how treatment arm and diabetes characteristics
      were associated with LUTS using logistic regression. RESULTS: Of the 591 men who
      completed the AUASI questions, nearly 20% (n = 115) had AUASI scores in the
      moderate to severe category for LUTS (AUASI score >or=8). No associations were
      observed between LUTS and treatment arm, or A1C levels at the DCCT baseline or
      end-of-study or at the year 10 EDIC (UroEDIC) examination. Of the diabetes
      complications studied, only erectile dysfunction at the UroEDIC examination was
      associated with LUTS. CONCLUSIONS: These data from the UroEDIC cohort do not
      support the assumption that intensive glycemic control results in decreased lower
      urinary tract symptom severity in men with type 1 diabetes. This result may be
      due to a true lack of effect, or it may be due to other factors, for example, the
      relatively young age of the cohort.

PMID- 19171726
TI  - Cost-efficacy of surgically induced weight loss for the management of type 2
      diabetes: a randomized controlled trial.
AB  - OBJECTIVE: To determine the within-trial cost-efficacy of surgical therapy
      relative to conventional therapy for achieving remission of recently diagnosed
      type 2 diabetes in class I and II obese patients. RESEARCH DESIGN AND METHODS:
      Efficacy results were derived from a 2-year randomized controlled trial. A health
      sector perspective was adopted, and within-trial intervention costs included
      gastric banding surgery, mitigation of complications, outpatient medical
      consultations, medical investigations, pathology, weight loss therapies, and
      medication. Resource use was measured based on data drawn from a trial database
      and patient medical records and valued based on private hospital costs and
      government schedules in 2006 Australian dollars (AUD). An incremental cost
      effectiveness analysis was undertaken. RESULTS: Mean 2-year intervention costs
      per patient were 13,400 AUD for surgical therapy and 3,400 AUD for conventional
      therapy, with laparoscopic adjustable gastric band (LAGB) surgery accounting for
      85% of the difference. Outpatient medical consultation costs were three times
      higher for surgical patients, whereas medication costs were 1.5 times higher for
      conventional patients. The cost differences were primarily in the first 6 months
      of the trial. Relative to conventional therapy, the incremental cost
      effectiveness ratio for surgical therapy was 16,600 AUD per case of diabetes
      remitted (currency exchange: 1 AUD = 0.74 USD). CONCLUSIONS: Surgical therapy
      appears to be a cost-effective option for managing type 2 diabetes in class I and
      II obese patients.

PMID- 19171727
TI  - Quality of life and quality of care in patients with diabetes experiencing
      different models of care.
AB  - OBJECTIVE: To study variation in quality of life and quality of care in patients
      with diabetes experiencing three different models of care: traditional hospital
      care, hospital/general practitioner (GP) shared care, and structured GP care.
      RESEARCH DESIGN AND METHODS: A cross-sectional study involving 1,456 patients
      with diabetes (71% response rate) was conducted. Quality of life was assessed
      with the Audit of Diabetes-Dependent Quality of Life (ADDQoL) instrument and
      quality of care with a 10-point process-of-care report card. RESULTS: The
      adjusted odds ratio (OR) for a high (upper quartile) ADDQoL score was
      significantly increased in the structured care relative to the traditional
      hospital care group (OR 1.7 [95% CI 1.2-2.5]). A significantly higher proportion
      of structured GP care patients reported compliance with seven or more key process
      of-care measures compared with the other models of care. CONCLUSIONS: Diabetes
      quality of life may be enhanced when care is provided in a primary care setting
      without compromising quality of care.

PMID- 19171728
TI  - Insulin resistance is associated with decreased quadriceps muscle strength in
      nondiabetic adults aged >or=70 years.
AB  - OBJECTIVE: Lower-limb muscle strength is reduced in many people with diabetes. In
      this study, we examined whether quadriceps muscle strength is reduced in relation
      to insulin resistance in well-functioning ambulatory nondiabetic individuals.
      RESEARCH DESIGN AND METHODS: Participants (age >or=70 years) underwent dual
      energy X-ray absorptiometry (DEXA) scanning to ascertain muscle and fat mass,
      tests of quadriceps strength, computed tomography scanning of the quadriceps to
      gauge muscle lipid content, and fasting insulin and glucose level measurements
      from which homeostasis model assessment of insulin resistance (HOMA-IR) was
      derived. RESULTS: In regression analysis, quadriceps strength per kilogram of
      muscle mass was negatively associated (P < 0.0001) with HOMA-IR independent of
      other factors negatively associated with strength such as increased age, female
      sex, low-physical activity, impaired fasting glucose, and increased total body
      fat. Muscle lipid content was not associated with strength. CONCLUSIONS: A small
      decrease in quadriceps muscle force is associated with increased HOMA-IR in well
      functioning nondiabetic adults, suggesting that diminished quadriceps muscle
      strength begins before diabetes.

PMID- 19171729
TI  - Topics in type 2 diabetes and insulin resistance.

PMID- 19171730
TI  - Gabapentin extended release for the treatment of painful diabetic peripheral
      neuropathy: efficacy and tolerability in a double-blind, randomized, controlled
      clinical trial.

PMID- 19171731
TI  - Impaired postprandial metabolism of apolipoprotein B48-containing remnant
      particles in normolipidemic subjects with brittle type 1 diabetes.

PMID- 19171732
TI  - Exenatide-associated ischemic renal failure.

PMID- 19171733
TI  - Impact of white-coat hypertension on microvascular complications in type 2
      diabetes: response to Kramer et al.

PMID- 19171735
TI  - Relationship between baseline glycemic control and cognitive function in
      individuals with type 2 diabetes and other cardiovascular risk factors: the
      action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD
      MIND) trial.
AB  - OBJECTIVE: Diabetes is associated with cognitive decline and dementia. However,
      the relationship between the degree of hyperglycemia and cognitive status remains
      unclear. This was explored using baseline cognitive measures collected in the
      ongoing Memory in Diabetes (MIND) substudy of the Action to Control
      Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS: The
      relationship of A1C and fasting plasma glucose (FPG) levels to performance on
      four cognitive tests was assessed, adjusting for age and other determinants of
      cognitive status. The tests were the Digit Symbol Substitution Test (DSST), Mini
      Mental Status Examination (MMSE), Rey Auditory Verbal Learning Test, and Stroop
      Test. RESULTS: A statistically significant age-adjusted association was observed
      between the A1C level and the score on all four cognitive tests. Specifically, a
      1% higher A1C value was associated with a significant 1.75-point lower DSST score
      (95% CI -1.22 to -2.28; P < 0.0001), a 0.20-point lower MMSE score (-0.11 to 
      0.28; P < 0.0001), a 0.11-point lower memory score (-0.02 to -0.19, P = 0.0142),
      and a worse score (i.e., 0.75 s more) on the Stroop Test (1.31-0.19, P = 0.0094).
      The association between the DSST score and A1C persisted in all multiple linear
      regression models. FPG was not associated with test performance. CONCLUSIONS:
      Higher A1C levels are associated with lower cognitive function in individuals
      with diabetes. The effect of glucose lowering on cognitive function will be
      determined by the ongoing ACCORD-MIND trial.

PMID- 19171736
TI  - How our current medical care system fails people with diabetes: lack of timely,
      appropriate clinical decisions.

PMID- 19171745
TI  - Regulating glucagon secretion: somatostatin in the spotlight.

PMID- 19171746
TI  - Many HAPO returns: maternal glycemia and neonatal adiposity: new insights from
      the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study.

PMID- 19171747
TI  - The alpha-cell conundrum: ATP-sensitive K+ channels and glucose sensing.

PMID- 19171748
TI  - Inflammation, insulin resistance, and type 2 diabetes: back to the future?

PMID- 19171753
TI  - Jodi Nunnari: keeping an eye on mitochondrial inheritance. Interview by Caitlin
      Sedgwick.

PMID- 19171749
TI  - Imatinib mesylate reduces endoplasmic reticulum stress and induces remission of
      diabetes in db/db mice.
AB  - OBJECTIVE: Imatinib has been reported to induce regression of type 2 diabetes in
      chronic leukemia patients. However, the mechanism of diabetes amelioration by
      imatinib is unknown, and it is uncertain whether imatinib has effects on type 2
      diabetes itself without other confounding diseases like leukemia. We studied the
      effect of imatinib on diabetes in db/db mice and investigated possible
      mechanism's underlying improved glycemic control by imatinib. RESEARCH DESIGN AND
      METHODS: Glucose tolerance and insulin tolerance tests were done after daily
      intraperitoneal injection of 25 mg/kg imatinib into db/db and C57BL/6 mice for 4
      weeks. Insulin signaling and endoplasmic reticulum stress responses were studied
      by Western blotting. beta-Cell mass and apoptotic beta-cell number were
      determined by combined terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling (TUNEL) staining and insulin immunohistochemistry. The in vitro
      effect of imatinib was studied using HepG2 cells. RESULTS: Imatinib induced
      remission of diabetes in db/db mice and amelioration of insulin resistance.
      Expression of endoplasmic reticulum stress markers in the liver and adipose
      tissues of db/db mice, such as phospho-PERK, phospho-eIF2alpha, TRB3, CHOP, and
      phospho-c-Jun NH(2)-terminal kinase, was reduced by imatinib. Insulin receptor
      substrate-1 tyrosine phosphorylation and Akt phosphorylation after insulin
      administration were improved by imatinib. Serum aminotransferase levels and
      hepatic triglyceride contents were decreased by imatinib. Pancreatic beta-cell
      mass was increased by imatinib, accompanied by decreased TUNEL(+) beta-cell and
      increased BrdU(+) beta-cell numbers. Imatinib attenuated endoplasmic reticulum
      stress in hepatoma cells in vitro. CONCLUSIONS: Imatinib ameliorated endoplasmic
      reticulum stress and induced remission of diabetes in db/db mice. Imatinib or
      related compounds could be used as therapeutic agents against type 2 diabetes and
      metabolic syndrome.

PMID- 19171754
TI  - Translocation or just location? Pseudopodia affect fluorescent signals.
AB  - The use of fluorescent probes is one of the most powerful techniques for gaining
      spatial and temporal knowledge of dynamic events within living cells. Localized
      increases in the signal from cytosolic fluorescent protein constructs, for
      example, are frequently used as evidence for translocation of proteins to
      specific sites within the cell. However, differences in optical and geometrical
      properties of cytoplasm can influence the recorded intensity of the probe signal.
      Pseudopodia are especially problematic because their cytoplasmic properties can
      cause abrupt increases in fluorescent signal of both GFP and fluorescein.
      Investigators should therefore be cautious when interpreting fluorescence changes
      within a cell, as these can result from either translocation of the probe or
      changes in the optical properties of the milieu surrounding the probe.

PMID- 19171755
TI  - TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic
      receptor for bacteria.
AB  - Phagocytosis, which is essential for the immune response to pathogens, is
      initiated by specific interactions between pathogens and cell surface receptors
      expressed by phagocytes. This study identifies triggering receptor expressed on
      myeloid cells 2 (TREM-2) and its signaling counterpart DAP12 as a molecular
      complex that promotes phagocytosis of bacteria. Expression of TREM-2-DAP12
      enables nonphagocytic Chinese hamster ovary cells to internalize bacteria. This
      function depends on actin cytoskeleton dynamics and the activity of the small
      guanosine triphosphatases Rac and Cdc42. Internalization also requires src kinase
      activity and tyrosine phosphorylation. In bone marrow-derived macrophages,
      phagocytosis is decreased in the absence of DAP12 and can be restored by
      expression of TREM-2-DAP12. Depletion of TREM-2 inhibits both binding and uptake
      of bacteria. Finally, TREM-2-dependent phagocytosis is impaired in Syk-deficient
      macrophages. This study highlights a novel role for TREM-2-DAP12 in the immune
      response to bacterial pathogens.

PMID- 19171756
TI  - The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole
      reduplication.
AB  - Restricting centriole duplication to once per cell cycle is critical for
      chromosome segregation and genomic stability, but the mechanisms underlying this
      block to reduplication are unclear. Genetic analyses have suggested an
      involvement for Skp/Cullin/F box (SCF)-class ubiquitin ligases in this process.
      In this study, we describe a mechanism to prevent centriole reduplication in
      Drosophila melanogaster whereby the SCF E3 ubiquitin ligase in complex with the F
      box protein Slimb mediates proteolytic degradation of the centrosomal regulatory
      kinase Plk4. We identified SCF(Slimb) as a regulator of centriole duplication via
      an RNA interference (RNAi) screen of Cullin-based ubiquitin ligases. We found
      that Plk4 binds to Slimb and is an SCF(Slimb) target. Both Slimb and Plk4
      localize to centrioles, with Plk4 levels highest at mitosis and absent during S
      phase. Using a Plk4 Slimb-binding mutant and Slimb RNAi, we show that Slimb
      regulates Plk4 localization to centrioles during interphase, thus regulating
      centriole number and ensuring the block to centriole reduplication.

PMID- 19171757
TI  - Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1
      and S-glutathionylation of Fas.
AB  - Reactive oxygen species (ROS) increase ligation of Fas (CD95), a receptor
      important for regulation of programmed cell death. Glutathionylation of reactive
      cysteines represents an oxidative modification that can be reversed by
      glutaredoxins (Grxs). The goal of this study was to determine whether Fas is
      redox regulated under physiological conditions. In this study, we demonstrate
      that stimulation with Fas ligand (FasL) induces S-glutathionylation of Fas at
      cysteine 294 independently of nicotinamide adenine dinucleotide phosphate reduced
      oxidase-induced ROS. Instead, Fas is S-glutathionylated after caspase-dependent
      degradation of Grx1, increasing subsequent caspase activation and apoptosis.
      Conversely, overexpression of Grx1 attenuates S-glutathionylation of Fas and
      partially protects against FasL-induced apoptosis. Redox-mediated Fas
      modification promotes its aggregation and recruitment into lipid rafts and
      enhances binding of FasL. As a result, death-inducing signaling complex formation
      is also increased, and subsequent activation of caspase-8 and -3 is augmented.
      These results define a novel redox-based mechanism to propagate Fas-dependent
      apoptosis.

PMID- 19171758
TI  - Kank attenuates actin remodeling by preventing interaction between IRSp53 and
      Rac1.
AB  - In this study, insulin receptor substrate (IRS) p53 is identified as a binding
      partner for Kank, a kidney ankyrin repeat-containing protein that functions to
      suppress cell proliferation and regulate the actin cytoskeleton. Kank
      specifically inhibits the binding of IRSp53 with active Rac1 (Rac1(G12V)) but not
      Cdc42 (cdc42(G12V)) and thus inhibits the IRSp53-dependent development of
      lamellipodia without affecting the formation of filopodia. Knockdown (KD) of Kank
      by RNA interference results in increased lamellipodial development, whereas KD of
      both Kank and IRSp53 has little effect. Moreover, insulin-induced membrane
      ruffling is inhibited by overexpression of Kank. Kank also suppresses integrin
      dependent cell spreading and IRSp53-induced neurite outgrowth. Our results
      demonstrate that Kank negatively regulates the formation of lamellipodia by
      inhibiting the interaction between Rac1 and IRSp53.

PMID- 19171759
TI  - Actin filament dynamics are dominated by rapid growth and severing activity in
      the Arabidopsis cortical array.
AB  - Metazoan cells harness the power of actin dynamics to create cytoskeletal arrays
      that stimulate protrusions and drive intracellular organelle movements. In plant
      cells, the actin cytoskeleton is understood to participate in cell elongation;
      however, a detailed description and molecular mechanism(s) underpinning filament
      nucleation, growth, and turnover are lacking. Here, we use variable-angle
      epifluorescence microscopy (VAEM) to examine the organization and dynamics of the
      cortical cytoskeleton in growing and nongrowing epidermal cells. One population
      of filaments in the cortical array, which most likely represent single actin
      filaments, is randomly oriented and highly dynamic. These filaments grow at rates
      of 1.7 microm/s, but are generally short-lived. Instead of depolymerization at
      their ends, actin filaments are disassembled by severing activity. Remodeling of
      the cortical actin array also features filament buckling and straightening
      events. These observations indicate a mechanism inconsistent with treadmilling.
      Instead, cortical actin filament dynamics resemble the stochastic dynamics of an
      in vitro biomimetic system for actin assembly.

PMID- 19171760
TI  - Integrin alpha3beta1-dependent beta-catenin phosphorylation links epithelial Smad
      signaling to cell contacts.
AB  - Injury-initiated epithelial to mesenchymal transition (EMT) depends on contextual
      signals from the extracellular matrix, suggesting a role for integrin signaling.
      Primary epithelial cells deficient in their prominent laminin receptor,
      alpha3beta1, were found to have a markedly blunted EMT response to TGF-beta1. A
      mechanism for this defect was explored in alpha3-null cells reconstituted with
      wild-type (wt) alpha3 or point mutants unable to engage laminin 5 (G163A) or
      epithelial cadherin (E-cadherin; H245A). After TGF-beta1 stimulation, wt
      epithelial cells but not cells expressing the H245A mutant internalize complexes
      of E-cadherin and TGF-beta1 receptors, generate phospho-Smad2 (p-Smad2)-pY654
      beta-catenin complexes, and up-regulate mesenchymal target genes. Although Smad2
      phosphorylation is normal, p-Smad2-pY654-beta-catenin complexes do not form in
      the absence of alpha3 or when alpha3beta1 is mainly engaged on laminin 5 or E
      cadherin in adherens junctions, leading to attenuated EMT. These findings
      demonstrate that alpha3beta1 coordinates cross talk between beta-catenin and Smad
      signaling pathways as a function of extracellular contact cues and thereby
      regulates responses to TGF-beta1 activation.

PMID- 19171763
TI  - Antibody to the dendritic cell surface activation antigen CD83 prevents acute
      graft-versus-host disease.
AB  - Allogeneic (allo) hematopoietic stem cell transplantation is an effective therapy
      for hematological malignancies but it is limited by acute graft-versus-host
      disease (GVHD). Dendritic cells (DC) play a major role in the allo T cell
      stimulation causing GVHD. Current immunosuppressive measures to control GVHD
      target T cells but compromise posttransplant immunity in the patient,
      particularly to cytomegalovirus (CMV) and residual malignant cells. We showed
      that treatment of allo mixed lymphocyte cultures with activated human DC
      depleting CD83 antibody suppressed alloproliferation but preserved T cell
      numbers, including those specific for CMV. We also tested CD83 antibody in the
      human T cell-dependent peripheral blood mononuclear cell transplanted SCID (hu
      SCID) mouse model of GVHD. We showed that this model requires human DC and that
      CD83 antibody treatment prevented GVHD but, unlike conventional
      immunosuppressants, did not prevent engraftment of human T cells, including
      cytotoxic T lymphocytes (CTL) responsive to viruses and malignant cells.
      Immunization of CD83 antibody-treated hu-SCID mice with irradiated human leukemic
      cell lines induced allo antileukemic CTL effectors in vivo that lysed (51)Cr
      labeled leukemic target cells in vitro without further stimulation. Antibodies
      that target activated DC are a promising new therapeutic approach to the control
      of GVHD.

PMID- 19171762
TI  - Posttranslational regulation of the NKG2D ligand Mult1 in response to cell
      stress.
AB  - NKG2D is a major stimulatory receptor expressed by natural killer (NK) cells and
      some T cells. The receptor recognizes major histocompatibility complex class I
      like cell surface ligands that are poorly expressed by normal tissues but are
      often induced in transformed and infected cells. The existence of several NKG2D
      ligands in each individual, some with strikingly divergent protein sequences,
      raises the possibility that different ligands are regulated by distinct disease
      associated stresses. The transcripts for some ligands, including murine UL16
      binding proteinlike transcript 1 (Mult1), are abundant in certain normal tissues
      where cell surface expression is absent, suggesting the existence of
      translational or posttranslational regulation. We report here that under normal
      conditions, Mult1 protein undergoes ubiquitination dependent on lysines in its
      cytoplasmic tail and lysosomal degradation. Mult1 degradation and ubiquitination
      is reduced in response to stress imparted by heat shock or ultraviolet
      irradiation, but not by other forms of genotoxicity, providing a novel mechanism
      for stress-mediated cellular control of NKG2D ligand expression.

PMID- 19171764
TI  - Anaphylactic shock depends on endothelial Gq/G11.
AB  - Anaphylactic shock is a severe allergic reaction involving multiple organs
      including the bronchial and cardiovascular system. Most anaphylactic mediators,
      like platelet-activating factor (PAF), histamine, and others, act through G
      protein-coupled receptors, which are linked to the heterotrimeric G proteins
      G(q)/G(11), G(12)/G(13), and G(i). The role of downstream signaling pathways
      activated by anaphylactic mediators in defined organs during anaphylactic
      reactions is largely unknown. Using genetic mouse models that allow for the
      conditional abrogation of G(q)/G(11)- and G(12)/G(13)-mediated signaling pathways
      by inducible Cre/loxP-mediated mutagenesis in endothelial cells (ECs), we show
      that G(q)/G(11)-mediated signaling in ECs is required for the opening of the
      endothelial barrier and the stimulation of nitric oxide formation by various
      inflammatory mediators as well as by local anaphylaxis. The systemic effects of
      anaphylactic mediators like histamine and PAF, but not of bacterial
      lipopolysaccharide (LPS), are blunted in mice with endothelial G alpha(q)/G
      alpha(11) deficiency. Mice with endothelium-specific G alpha(q)/G alpha(11)
      deficiency, but not with G alpha(12)/G alpha(13) deficiency, are protected
      against the fatal consequences of passive and active systemic anaphylaxis. This
      identifies endothelial G(q)/G(11)-mediated signaling as a critical mediator of
      fatal systemic anaphylaxis and, hence, as a potential new target to prevent or
      treat anaphylactic reactions.

PMID- 19171765
TI  - Increasing functional avidity of TCR-redirected T cells by removing defined N
      glycosylation sites in the TCR constant domain.
AB  - Adoptive transfer of T lymphocytes transduced with a T cell receptor (TCR) to
      impart tumor reactivity has been reported as a potential strategy to redirect
      immune responses to target cancer cells (Schumacher, T.N. 2002. Nat. Rev.
      Immunol. 2:512-519). However, the affinity of most TCRs specific for shared tumor
      antigens that can be isolated is usually low. Thus, strategies to increase the
      affinity of TCRs or the functional avidity of TCR-transduced T cells might be
      therapeutically beneficial. Because glycosylation affects the flexibility,
      movement, and interactions of surface molecules, we tested if selectively
      removing conserved N-glycoslyation sites in the constant regions of TCR alpha or
      beta chains could increase the functional avidity of T cells transduced with such
      modified TCRs. We observed enhanced functional avidity and improved recognition
      of tumor cells by T cells harboring TCR chains with reduced N-glycosylation
      (DeltaTCR) as compared with T cells with wild-type (WT) TCR chains. T cells
      transduced with WT or DeltaTCR chains bound tetramer equivalently at 4 degrees C,
      but tetramer binding was enhanced at 37 degrees C, predominantly as a result of
      reduced tetramer dissociation. This suggested a temperature-dependent mechanism
      such as TCR movement in the cell surface or structural changes of the TCR
      allowing improved multimerization. This strategy was effective with mouse and
      human TCRs specific for different antigens and, thus, should be readily
      translated to TCRs with any specificity.

PMID- 19171766
TI  - Differential rates of replacement of human dermal dendritic cells and macrophages
      during hematopoietic stem cell transplantation.
AB  - Animal models of hematopoietic stem cell transplantation have been used to
      analyze the turnover of bone marrow-derived cells and to demonstrate the critical
      role of recipient antigen-presenting cells (APC) in graft versus host disease
      (GVHD). In humans, the phenotype and lineage relationships of myeloid-derived
      tissue APC remain incompletely understood. It has also been proposed that the
      risk of acute GVHD, which extends over many months, is related to the protracted
      survival of certain recipient APC. Human dermis contains three principal subsets
      of CD45(+)HLA-DR(+) cells: CD1a(+)CD14(-) DC, CD1a(-)CD14(+) DC, and CD1a(
      )CD14(+)FXIIIa(+) macrophages. In vitro, each subset has characteristic
      properties. After transplantation, both CD1a(+) and CD14(+) DC are rapidly
      depleted and replaced by donor cells, but recipient macrophages can be found in
      GVHD lesions and may persist for many months. Macrophages isolated from normal
      dermis secrete proinflammatory cytokines. Although they stimulate little
      proliferation of naive or memory CD4(+) T cells, macrophages induce cytokine
      expression in memory CD4(+) T cells and activation and proliferation of CD8(+) T
      cells. These observations suggest that dermal macrophages and DC are from
      distinct lineages and that persistent recipient macrophages, although unlikely to
      initiate alloreactivity, may contribute to GVHD by sustaining the responses of
      previously activated T cells.

PMID- 19171768
TI  - Kudos to reviewers for the JGP: you make our science better.

PMID- 19171767
TI  - Human CD4+ T cell recent thymic emigrants are identified by protein tyrosine
      kinase 7 and have reduced immune function.
AB  - CD4(+) recent thymic emigrants (RTEs) comprise a clinically and immunologically
      important T cell population that indicates thymic output and that is essential
      for maintaining a diverse alphabeta-T cell receptor (TCR) repertoire of the naive
      CD4(+) T cell compartment. However, their frequency and function are poorly
      understood because no known surface markers distinguish them from older non-RTE
      naive CD4(+) T cells. We demonstrate that protein tyrosine kinase 7 (PTK7) is a
      novel marker for human CD4(+) RTEs. Consistent with their recent thymic origin,
      human PTK7(+) RTEs contained higher levels of signal joint TCR gene excision
      circles and were more responsive to interleukin (IL)-7 compared with PTK7(-)
      naive CD4(+) T cells, and rapidly decreased after complete thymectomy.
      Importantly, CD4(+) RTEs proliferated less and produced less IL-2 and interferon
      gamma than PTK7(-) naive CD4(+) T cells after alphabeta-TCR/CD3 and CD28
      engagement. This immaturity in CD4(+) RTE effector function may contribute to the
      reduced CD4(+) T cell immunity observed in contexts in which CD4(+) RTEs
      predominate, such as in the fetus and neonate or after immune reconstitution. The
      ability to identify viable CD4(+) RTEs by PTK7 staining should be useful for
      monitoring thymic output in both healthy individuals and in patients with genetic
      or acquired CD4(+) T cell immunodeficiencies.

PMID- 19171769
TI  - Decremental response to high-frequency trains of acetylcholine pulses but
      unaltered fractional Ca2+ currents in a panel of "slow-channel syndrome"
      nicotinic receptor mutants.
AB  - The slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the
      neuromuscular junction caused by gain-of-function mutations to the muscle
      nicotinic acetylcholine (ACh) receptor (AChR). Although it is clear that the
      slower deactivation time course of the ACh-elicited currents plays a central role
      in the etiology of this disease, it has been suggested that other abnormal
      properties of these mutant receptors may also be critical in this respect. We
      characterized the kinetics of a panel of five SCCMS AChRs (alphaS269I, betaV266M,
      epsilonL221F, epsilonT264P, and epsilonL269F) at the ensemble level in rapidly
      perfused outside-out patches. We found that, for all of these mutants, the peak
      current amplitude decreases along trains of nearly saturating ACh pulses
      delivered at physiologically relevant frequencies in a manner that is consistent
      with enhanced entry into desensitization during the prolonged deactivation phase.
      This suggests that the increasingly reduced availability of activatable AChRs
      upon repetitive stimulation may well contribute to the fatigability and weakness
      of skeletal muscle that characterize this disease. Also, these results emphasize
      the importance of explicitly accounting for entry into desensitization as one of
      the pathways for burst termination, if meaningful mechanistic insight is to be
      inferred from the study of the effect of these naturally occurring mutations on
      channel function. Applying a novel single-channel-based approach to estimate the
      contribution of Ca(2+) to the total cation currents, we also found that none of
      these mutants affects the Ca(2+)-conduction properties of the AChR to an extent
      that seems to be of physiological importance. Our estimate of the Ca(2+)-carried
      component of the total (inward) conductance of wild-type and SCCMS AChRs in the
      presence of 150 mM Na(+), 1.8 mM Ca(2+), and 1.7 mM Mg(2+) on the extracellular
      side of cell-attached patches turned out be in the 5.0-9.4 pS range, representing
      a fractional Ca(2+) current of approximately 14%, on average. Remarkably, these
      values are nearly identical to those we estimated for the NR1-NR2A N-methyl-d
      aspartate receptor (NMDAR), which has generally been considered to be the main
      neurotransmitter-gated pathway of Ca(2+) entry into the cell. Our estimate of the
      rat NMDAR Ca(2+) conductance (using the same single-channel approach as for the
      AChR but in the nominal absence of extracellular Mg(2+)) was 7.9 pS,
      corresponding to a fractional Ca(2+) current of 13%.

PMID- 19171770
TI  - Pentobarbital produces activation and block of {alpha}1{beta}2{gamma}2S GABAA
      receptors in rapidly perfused whole cells and membrane patches: divergent results
      can be explained by pharmacokinetics.
AB  - Millimolar concentrations of the barbiturate pentobarbital (PB) activate gamma
      aminobutyric acid (GABA) type A receptors (GABARs) and cause blockade reported by
      a paradoxical current increase or "tail" upon washout. To explore the mechanism
      of blockade, we investigated PB-triggered currents of recombinant
      alpha(1)beta(2)gamma(2S) GABARs in whole cells and outside-out membrane patches
      using rapid perfusion. Whole cell currents showed characteristic bell-shaped
      concentration dependence where high concentrations triggered tail currents with
      peak amplitudes similar to those during PB application. Tail current time courses
      could not be described by multi-exponential functions at high concentrations (>
      or =3,000 microM). Deactivation time course decayed over seconds and was slowed
      by increasing PB concentration and application time. In contrast, macropatch tail
      currents manifested eightfold greater relative amplitude, were described by multi
      exponential functions, and had millisecond rise times; deactivation occurred over
      fractions of seconds and was insensitive to PB concentration and application
      time. A parsimonious gating model was constructed that accounts for macropatch
      results ("patch" model). Lipophilic drug molecules migrate slowly through cells
      due to avid partitioning into lipophilic subcellular compartments. Inclusion of
      such a pharmacokinetic compartment into the patch model introduced a slow kinetic
      component in the extracellular exchange time course, thereby providing
      recapitulation of divergent whole cell results. GABA co-application potentiated
      PB blockade. Overall, the results indicate that block is produced by PB
      concentrations sixfold lower than for activation involving at least three
      inhibitory PB binding sites, suggest a role of blocked channels in GABA-triggered
      activity at therapeutic PB concentrations, and raise an important technical
      question regarding the effective rate of exchange during rapid perfusion of whole
      cells with PB.

PMID- 19171771
TI  - Four Ca2+ ions activate TRPM2 channels by binding in deep crevices near the pore
      but intracellularly of the gate.
AB  - TRPM2 is a tetrameric Ca(2+)-permeable channel involved in immunocyte respiratory
      burst and in postischaemic neuronal death. In whole cells, TRPM2 activity
      requires intracellular ADP ribose (ADPR) and intra- or extracellular Ca(2+), but
      the mechanism and the binding sites for Ca(2+) activation remain unknown. Here we
      study TRPM2 gating in inside-out patches while directly controlling intracellular
      ligand concentrations. Concentration jump experiments at various voltages and
      Ca(2+) dependence of steady-state single-channel gating kinetics provide
      unprecedented insight into the molecular mechanism of Ca(2+) activation. In
      patches excised from Xenopus laevis oocytes expressing human TRPM2, coapplication
      of intracellular ADPR and Ca(2+) activated approximately 50-pS nonselective
      cation channels; K(1/2) for ADPR was approximately 1 microM at saturating Ca(2+).
      Intracellular Ca(2+) dependence of TRPM2 steady-state opening and closing rates
      (at saturating [ADPR] and low extracellular Ca(2+)) reveals that Ca(2+)
      activation is a consequence of tighter binding of Ca(2+) in the open rather than
      in the closed channel conformation. Four Ca(2+) ions activate TRPM2 with a Monod
      Wymann-Changeux mechanism: each binding event increases the open-closed
      equilibrium constant approximately 33-fold, producing altogether 10(6)-fold
      activation. Experiments in the presence of 1 mM of free Ca(2+) on the
      extracellular side clearly show that closed channels do not sense extracellular
      Ca(2+), but once channels have opened Ca(2+) entering passively through the pore
      slows channel closure by keeping the "activating sites" saturated, despite rapid
      continuous Ca(2+)-free wash of the intracellular channel surface. This effect of
      extracellular Ca(2+) on gating is gradually lost at progressively depolarized
      membrane potentials, where the driving force for Ca(2+) influx is diminished.
      Thus, the activating sites lie intracellularly from the gate, but in a shielded
      crevice near the pore entrance. Our results suggest that in intact cells that
      contain micromolar ADPR a single brief puff of Ca(2+) likely triggers prolonged,
      self-sustained TRPM2 activity.

PMID- 19171772
TI  - Dynamic coupling of voltage sensor and gate involved in closed-state inactivation
      of kv4.2 channels.
AB  - Voltage-gated potassium channels related to the Shal gene of Drosophila (Kv4
      channels) mediate a subthreshold-activating current (I(SA)) that controls
      dendritic excitation and the backpropagation of action potentials in neurons. Kv4
      channels also exhibit a prominent low voltage-induced closed-state inactivation,
      but the underlying molecular mechanism is poorly understood. Here, we examined a
      structural model in which dynamic coupling between the voltage sensors and the
      cytoplasmic gate underlies inactivation in Kv4.2 channels. We performed an
      alanine-scanning mutagenesis in the S4-S5 linker, the initial part of S5, and the
      distal part of S6 and functionally characterized the mutants under two-electrode
      voltage clamp in Xenopus oocytes. In a large fraction of the mutants (>80%)
      normal channel function was preserved, but the mutations influenced the
      likelihood of the channel to enter the closed-inactivated state. Depending on the
      site of mutation, low-voltage inactivation kinetics were slowed or accelerated,
      and the voltage dependence of steady-state inactivation was shifted positive or
      negative. Still, in some mutants these inactivation parameters remained
      unaffected. Double mutant cycle analysis based on kinetic and steady-state
      parameters of low-voltage inactivation revealed that residues known to be
      critical for voltage-dependent gate opening, including Glu 323 and Val 404, are
      also critical for Kv4.2 closed-state inactivation. Selective redox modulation of
      corresponding double-cysteine mutants supported the idea that these residues are
      involved in a dynamic coupling, which mediates both transient activation and
      closed-state inactivation in Kv4.2 channels.

PMID- 19171773
TI  - Beyond oversights, lies, and pies in the sky: exaggeration as goal projection.
AB  - The adaptiveness of overly positive self-evaluation is heavily debated. The
      present research emphasizes that costs and benefits of positive biases are
      contingent upon their underlying motives. Five studies explored psychological and
      performance correlates of the tendency to exaggerate academic performance.
      Students who exaggerated in a private reporting context showed greater
      achievement motivation and positive affect (Study 1), challenge and approach
      orientations (Study 2), and observer-rated composure during a stressful mock job
      interview (Study 3). Moreover, exaggeration predicted subsequent academic
      improvements. This form of exaggeration apparently reflects an adaptive tendency
      to project positive goals onto self-reports. In contrast, exaggeration in a more
      public context was associated with social desirability motives and not with
      positive affect, approach/challenge motives, or improvement (Study 4). Making
      actual performance salient (by highlighting that records would be checked)
      reduced exaggeration; students who exaggerated in this context did not improve
      over time, instead showing performance decrements (Study 5).

PMID- 19171774
TI  - Priming media stereotypes reduces support for social welfare policies: the
      mediating role of empathy.
AB  - Two experiments involving White participants tested the influence of media-based
      priming of Black stereotypes on support for government policy that assisted Black
      versus White persons-in-need. Experiment 1 showed that priming the "Black
      criminal" stereotype through exposure to photographs of Blacks looting after
      Hurricane Katrina reduced policy support for Black evacuees-in-need but did not
      influence support responses toward White evacuees-in-need. Experiment 2 showed
      that priming the "promiscuous Black female" stereotype through exposure to sexual
      rap music reduced policy support for a Black pregnant woman-in-need but did not
      influence support responses toward a White pregnant woman-in-need. Further tests
      of mediated moderation demonstrated that in both experiments, the interactive
      influence of priming Black stereotypes and race of persons-in-need on policy
      support was mediated by empathic responding.

PMID- 19171775
TI  - Interpersonal predictors of stress generation.
AB  - Hammen (1991) provided evidence for a stress generation process in which
      individuals with a history of depression contributed to the occurrence of
      stressors, especially interpersonal and conflict events. However, few studies
      have examined the factors contributing to stress generation. This study examines
      aspects of individuals' interpersonal style, operationalized as attachment,
      dependency, and reassurance seeking, as predictors of conflict stress generation
      within romantic relationships. These effects were examined both prospectively
      over a 4-week period and cross-sectionally using a 14-day daily diary in a sample
      of female college students. Overall, there was significant evidence that
      interpersonal style contributes to the occurrence of interpersonal stressors.
      Specifically, anxious attachment and reassurance seeking prospectively predicted
      romantic conflict stress over a 4-week period, and a variety of interpersonal
      behaviors were associated with romantic conflict stressors on a daily basis.
      These results are interpreted in relation to previous literature, and limitations
      and directions for future research are discussed.

PMID- 19171776
TI  - A splicer that represses (translation).
AB  - Regulated translation and subcellular localization of maternal mRNAs underlies
      establishment of the antero-posterior axis in the Drosophila oocyte. In this
      issue of Genes & Development, Besse et al. (pp. 195-207) show that a molecule
      better known as a regulator of alternative splicing in the nucleus,
      polypyrimidine tract-binding protein (PTB), is required for repression of oskar
      mRNA in the cytoplasm. Their work suggests that PTB need not engage oskar mRNA in
      the nucleus for efficient repression, providing an important counterexample to
      the increasingly popular idea that cytoplasmic regulation initiates in the
      nucleus.

PMID- 19171777
TI  - Human papillomaviruses: a growing field.
AB  - A combination of functional studies on human papillomavirus (HPV) oncoproteins
      and epidemiological studies on persistence of HPV infection firmly established a
      role for HPV in the etiology of cervical cancers. Understanding the viral life
      cycle of HPVs has been more difficult. In this issue of Genes & Development, Wang
      et al. (pp. 181 - 194) describe an efficient method to propagate infectious HPV
      in differentiating epithelium, providing clear evidence for temporal separation
      of viral and cellular replication.

PMID- 19171778
TI  - Promoter-specific control of E. coli RNA polymerase by ppGpp and a general
      transcription factor.
AB  - The stringent response of Escherichia coli reflects a global influence of the
      nucleotide ppGpp on gene expression in response to nutrient starvation. For
      critical elements of the response, the target of ppGpp is RNA polymerase, which
      can be either repressed or activated in a promoter-dependent way. A small
      protein, DksA, which binds in the secondary channel of RNA polymerase, possibly
      along with other general regulatory factors, contributes to ppGpp-dependent
      transcription regulation. Rutherford and colleagues (pp. 236-248) identify
      mutations in genes for the core subunits of RNA polymerase that circumvent the
      need for DksA in the regulation; the sites of these mutations suggest that DksA
      acts allosterically through the RNA polymerase active site to destabilize
      transcription initiation complexes.

PMID- 19171779
TI  - Dscam and DSCAM: complex genes in simple animals, complex animals yet simple
      genes.
AB  - Cadherins and the immunoglobulin (Ig) proteins give rise to a multitude of
      surface receptors, which function as diverse cell adhesion molecules (CAMs) or
      signal-transducing receptors. These functions are often interdependent, and rely
      on a high degree of specificity in homophilic binding as well as heterophilic
      interactions. The Drosophila receptor Dscam is an exceptional example of
      homophilic binding specificity involved in a number of important biological
      processes, such as neural wiring and innate immunity. Combinatorial use of
      alternatively spliced Ig-domains enables the generation of an estimated 18,000
      isoform-specific homophilic receptor pairs. Although isoform diversity of Dscam
      is unique to arthropods, recent genetic analysis of vertebrate DSCAM (Down
      Syndrome Cell Adhesion Molecule) genes has revealed an intriguing conservation of
      molecular functions underlying neural wiring. This review covers the multiple
      functions of Dscam across different species highlighting its remarkable
      versatility as well as its conserved basic functions in neural development. We
      discuss how an unprecedented expansion of complex alternative splicing has been
      uniquely employed by arthropods to generate diverse surface receptors, important
      for cell-cell communication, molecular self-recognition in neurons, and innate
      immune defenses. We end with a speculative hypothesis reconciling the striking
      differences in Dscam and DSCAM gene structures with their conserved functions in
      molecular recognition underlying neural circuit formation.

PMID- 19171780
TI  - N-myc alters the fate of preneoplastic cells in a mouse model of medulloblastoma.
AB  - Studying the early stages of cancer can provide important insight into the
      molecular basis of the disease. We identified a preneoplastic stage in the
      patched (ptc) mutant mouse, a model for the brain tumor medulloblastoma.
      Preneoplastic cells (PNCs) are found in most ptc mutants during early adulthood,
      but only 15% of these animals develop tumors. Although PNCs are found in mice
      that develop tumors, the ability of PNCs to give rise to tumors has never been
      demonstrated directly, and the fate of cells that do not form tumors remains
      unknown. Using genetic fate mapping and orthotopic transplantation, we provide
      definitive evidence that PNCs give rise to tumors, and show that the predominant
      fate of PNCs that do not form tumors is differentiation. Moreover, we show that N
      myc, a gene commonly amplified in medulloblastoma, can dramatically alter the
      fate of PNCs, preventing differentiation and driving progression to tumors.
      Importantly, N-myc allows PNCs to grow independently of hedgehog signaling,
      making the resulting tumors resistant to hedgehog antagonists. These studies
      provide the first direct evidence that PNCs can give rise to tumors, and
      demonstrate that identification of genetic changes that promote tumor progression
      is critical for designing effective therapies for cancer.

PMID- 19171781
TI  - Differential DNA damage signaling accounts for distinct neural apoptotic
      responses in ATLD and NBS.
AB  - The MRN complex (Mre11/RAD50/NBS1) and ATM (ataxia telangiectasia, mutated) are
      critical for the cellular response to DNA damage. ATM disruption causes ataxia
      telangiectasia (A-T), while MRN dysfunction can lead to A-T-like disease (ATLD)
      or Nijmegen breakage syndrome (NBS). Neuropathology is a hallmark of these
      diseases, whereby neurodegeneration occurs in A-T and ATLD while microcephaly
      characterizes NBS. To understand the contrasting neuropathology resulting from
      Mre11 or Nbs1 hypomorphic mutations, we analyzed neural tissue from
      Mre11(ATLD1/ATLD1) and Nbs1(DeltaB/DeltaB) mice after genotoxic stress. We found
      a pronounced resistance to DNA damage-induced apoptosis after ionizing radiation
      or DNA ligase IV (Lig4) loss in the Mre11(ATLD1/ATLD1) nervous system that was
      associated with defective Atm activation and phosphorylation of its substrates
      Chk2 and p53. Conversely, DNA damage-induced Atm phosphorylation was defective in
      Nbs1(DeltaB/DeltaB) neural tissue, although apoptosis occurred normally. We also
      conditionally disrupted Lig4 throughout the nervous system using Nestin-cre
      (Lig4(Nes-Cre)), and while viable, these mice showed pronounced microcephaly and
      a prominent age-related accumulation of DNA damage throughout the brain. Either
      Atm-/- or Mre11(ATLD1/ATLD1) genetic backgrounds, but not Nbs1(DeltaB/DeltaB),
      rescued Lig4(Nes-Cre) microcephaly. Thus, DNA damage signaling in the nervous
      system is different between ATLD and NBS and likely explains their respective
      neuropathology.

PMID- 19171782
TI  - A general mechanism for transcription regulation by Oct1 and Oct4 in response to
      genotoxic and oxidative stress.
AB  - Oct1 and Oct4 are homologous transcription factors with similar DNA-binding
      specificities. Here we show that Oct1 is dynamically phosphorylated in vivo
      following exposure of cells to oxidative and genotoxic stress. We further show
      that stress regulates the selectivity of both proteins for specific DNA
      sequences. Mutation of conserved phosphorylation target DNA-binding domain
      residues in Oct1, and Oct4 confirms their role in regulating binding selectivity.
      Using chromatin immunoprecipitation, we show that association of Oct4 and Oct1
      with a distinct group of in vivo targets is inducible by stress, and that Oct1 is
      essential for a normal post-stress transcriptional response. Finally, using an
      unbiased Oct1 target screen we identify a large number of genes targeted by Oct1
      specifically under conditions of stress, and show that several of these inducible
      Oct1 targets are also inducibly bound by Oct4 in embryonic stem cells following
      stress exposure.

PMID- 19171783
TI  - A phosphorylation-acetylation switch regulates STAT1 signaling.
AB  - Cytokines such as interferons (IFNs) activate signal transducers and activators
      of transcription (STATs) via phosphorylation. Histone deacetylases (HDACs) and
      the histone acetyltransferase (HAT) CBP dynamically regulate STAT1 acetylation.
      Here we show that acetylation of STAT1 counteracts IFN-induced STAT1
      phosphorylation, nuclear translocation, DNA binding, and target gene expression.
      Biochemical and genetic experiments altering the HAT/HDAC activity ratio and
      STAT1 mutants reveal that a phospho-acetyl switch regulates STAT1 signaling via
      CBP, HDAC3, and the T-cell protein tyrosine phosphatase (TCP45). Strikingly,
      inhibition of STAT1 signaling via CBP-mediated acetylation is distinct from the
      functions of this HAT in transcriptional activation. STAT1 acetylation induces
      binding of TCP45, which catalyzes dephosphorylation and latency of STAT1. Our
      results provide a deeper understanding of the modulation of STAT1 activity. These
      findings reveal a new layer of physiologically relevant STAT1 regulation and
      suggest that a previously unidentified balance between phosphorylation and
      acetylation affects cytokine signaling.

PMID- 19171784
TI  - Allosteric control of Escherichia coli rRNA promoter complexes by DksA.
AB  - The Escherichia coli DksA protein inserts into the RNA polymerase (RNAP)
      secondary channel, modifying the transcription initiation complex so that
      promoters with specific kinetic characteristics are regulated by changes in the
      concentrations of ppGpp and NTPs. We used footprinting assays to determine the
      specific kinetic intermediate, RP(I), on which DksA acts. Genetic approaches
      identified substitutions in the RNAP switch regions, bridge helix, and trigger
      loop that mimicked, reduced, or enhanced DksA function on rRNA promoters. Our
      results indicate that DksA binding in the secondary channel of RP(I) disrupts
      interactions with promoter DNA at least 25 A away, between positions -6 and +6
      (the transcription start site is +1). We propose a working model in which the
      trigger loop and bridge helix transmit effects of DksA to the switch region(s),
      allosterically affecting switch residues that control clamp opening/closing
      and/or that interact directly with promoter DNA. DksA thus inhibits the
      transition to RP(I). Our results illustrate in mechanistic terms how
      transcription factors can regulate initiation promoter-specifically without
      interacting directly with DNA.

PMID- 19171785
TI  - Direct interaction between sensor kinase proteins mediates acute and chronic
      disease phenotypes in a bacterial pathogen.
AB  - The genome of the opportunistic pathogen Pseudomonas aeruginosa encodes over 60
      two-component sensor kinases and uses several (including RetS and GacS) to
      reciprocally regulate the production of virulence factors involved in the
      development of acute or chronic infections. We demonstrate that RetS modulates
      the phosphorylation state of GacS by a direct and specific interaction between
      these two membrane-bound sensors. The RetS-GacS interaction can be observed in
      vitro, in heterologous systems in vivo, and in P. aeruginosa. This function does
      not require the predicted RetS phosphorelay residues and provides a mechanism for
      integrating multiple signals without cross-phosphorylation from sensors to
      noncognate response regulators. These results suggest that multiple two-component
      systems found in a single bacterium can form multisensor signaling networks while
      maintaining specific phosphorelay pathways that remain insulated from detrimental
      cross-talk.

PMID- 19171786
TI  - Altered P2X7-receptor level and function in mouse models of Huntington's disease
      and therapeutic efficacy of antagonist administration.
AB  - The precise mechanism by which mutant huntingtin elicits its toxicity remains
      unknown. However, synaptic alterations and increased susceptibility to neuronal
      death are known contributors to Huntington's disease (HD) symptomatology. While
      decreased metabolism has long been associated with HD, recent findings have
      surprisingly demonstrated reduced neuronal apoptosis in Caenorhabditis elegans
      and Drosophila models of HD by drugs that diminish ATP production. Interestingly,
      extracellular ATP has been recently reported to elicit neuronal death through
      stimulation of P2X7 receptors. These are ATP-gated cation channels known to
      modulate neurotransmitter release from neuronal presynaptic terminals and to
      regulate cytokine production and release from microglia. We hypothesized that
      alteration in P2X7-mediated calcium permeability may contribute to HD synaptic
      dysfunction and increased neuronal apoptosis. Using mouse and cellular models of
      HD, we demonstrate increased P2X7-receptor level and altered P2X7-mediated
      calcium permeability in somata and terminals of HD neurons. Furthermore, cultured
      neurons expressing mutant huntingtin showed increased susceptibility to apoptosis
      triggered by P2X7-receptor stimulation. Finally, in vivo administration of the
      P2X7-antagonist Brilliant Blue-G (BBG) to HD mice prevented neuronal apoptosis
      and attenuated body weight loss and motor-coordination deficits. These in vivo
      data strongly suggest that altered P2X7-receptor level and function contribute to
      HD pathogenesis and highlight the therapeutic potential of P2X7 receptor
      antagonists.

PMID- 19171787
TI  - Dipping comes of age: the importance of nocturnal blood pressure.

PMID- 19171788
TI  - Prevalence and factors associated with circadian blood pressure patterns in
      hypertensive patients.
AB  - Ambulatory blood pressure (BP) monitoring has become useful in the diagnosis and
      management of hypertensive individuals. In addition to 24-hour values, the
      circadian variation of BP adds prognostic significance in predicting
      cardiovascular outcome. However, the magnitude of circadian BP patterns in large
      studies has hardly been noticed. Our aims were to determine the prevalence of
      circadian BP patterns and to assess clinical conditions associated with the
      nondipping status in groups of both treated and untreated hypertensive subjects,
      studied separately. Clinical data and 24-hour ambulatory BP monitoring were
      obtained from 42,947 hypertensive patients included in the Spanish Society of
      Hypertension Ambulatory Blood Pressure Monitoring Registry. They were 8384
      previously untreated and 34,563 treated hypertensives. Twenty-four-hour
      ambulatory BP monitoring was performed with an oscillometric device (SpaceLabs
      90207). A nondipping pattern was defined when nocturnal systolic BP dip was <10%
      of daytime systolic BP. The prevalence of nondipping was 41% in the untreated
      group and 53% in treated patients. In both groups, advanced age, obesity,
      diabetes mellitus, and overt cardiovascular or renal disease were associated with
      a blunted nocturnal BP decline (P<0.001). In treated patients, nondipping was
      associated with the use of a higher number of antihypertensive drugs but not with
      the time of the day at which antihypertensive drugs were administered. In
      conclusion, a blunted nocturnal BP dip (the nondipping pattern) is common in
      hypertensive patients. A clinical pattern of high cardiovascular risk is
      associated with nondipping, suggesting that the blunted nocturnal BP dip may be
      merely a marker of high cardiovascular risk.

PMID- 19171789
TI  - Exercise capacity and mortality in hypertensive men with and without additional
      risk factors.
AB  - We assessed the association between exercise capacity and mortality in
      hypertensive men with and without additional cardiovascular risk factors. A
      cohort of 4631 hypertensive veterans, who successfully completed a graded
      exercise test at the Veterans Affairs Medical Center in Washington, DC, and Palo
      Alto, California, was followed for 7.7+/-5.4 years (35,629 person-years) for all
      cause mortality. Fitness categories were established based on peak metabolic
      equivalent (MET) levels achieved. In each fitness category, we defined
      individuals with and without additional cardiovascular risk factors. Exercise
      capacity was the strongest predictor of all-cause mortality. The adjusted
      mortality risk was 13% lower for every 1-MET increase in exercise capacity.
      Compared with the very low fit (< or =5.0 MET), the adjusted risk was 34% lower
      for those achieving 5.1 to 7.0 MET (low fit; hazard ratio: 0.66; CI: 0.58 to
      0.76; P<0.001), 59% lower for the moderate fit (7.1 to 10.0 MET; hazard ratio:
      0.41; CI: 0.35 to 0.50; P<0.001), and 71% lower for the high-fit category (>10.0
      MET; hazard ratio: 0.29; CI: 0.21 to 0.40; P<0.001). Within the very-low-fit
      category, mortality risk was 47% higher for those with additional risk factors
      compared with individuals with no risk factors. This risk was eliminated for
      those in the next fitness category (5.1 to 7.0 MET) and was progressively reduced
      for the moderate and high-fit categories regardless of the presence or absence of
      additional risk factors. In conclusion, exercise capacity was the strongest
      predictor of all-cause mortality in hypertensive men. The increased risk imposed
      by low fitness and additional cardiovascular risk factors was eliminated by
      relatively small increases in exercise capacity and declined progressively with
      higher exercise capacity.

PMID- 19171790
TI  - Upward hypertension trends: changes in blood pressure or in antihypertensive
      treatment?

PMID- 19171791
TI  - Aortic calcification is associated with aortic stiffness and isolated systolic
      hypertension in healthy individuals.
AB  - Arterial stiffening is an independent predictor of mortality and underlies the
      development of isolated systolic hypertension (ISH). A number of factors regulate
      stiffness, but arterial calcification is also likely to be important. We tested
      the hypotheses that aortic calcification is associated with aortic stiffness in
      healthy individuals and that patients with ISH exhibit exaggerated aortic
      calcification compared with controls. A total of 193 healthy, medication-free
      subjects (mean age+/-SD: 66+/-8 years) were recruited from the community,
      together with 15 patients with resistant ISH. Aortic pulse wave velocity (PWV)
      was measured noninvasively, and aortic calcium content was quantified from high
      resolution, thoraco-lumbar computed tomography images using a volume scoring
      method. In healthy volunteers, calcification was positively and significantly
      associated with aortic PWV (r=0.6; P<0.0001) but was not related to augmentation
      index or brachial PWV. Calcification was significantly higher in treatment
      resistant and healthy subjects with ISH compared with controls (mean
      [interquartile range]: 1.92 [1.14 to 3.66], 0.84 [0.35 to 1.75], and 0.19 [0.1 to
      0.78] cm3, respectively; P<0.0001 for both). In a multiple regression model,
      aortic calcium was independently associated with aortic PWV along with age, mean
      arterial pressure, heart rate, and estimated glomerular filtration rate
      (R(2)=0.51; P<0.0001). Only age, calcium phosphate product, and aortic PWV were
      independently associated with calcification. These data suggest that
      calcification may be important in the process of aortic stiffening and the
      development of ISH. Calcification may underlie treatment resistance in ISH, and
      anticalcification strategies may present a novel therapy.

PMID- 19171792
TI  - Sex differences in sympathetic neural-hemodynamic balance: implications for human
      blood pressure regulation.
AB  - Among young normotensive men, a reciprocal balance between cardiac output and
      sympathetic nerve activity is important in the regulation of arterial pressure.
      In young women, the balance among cardiac output, peripheral resistance, and
      sympathetic nerve activity is unknown. Consequently, the aim of this study was to
      examine the relationship of cardiac output and total peripheral resistance to
      muscle sympathetic nerve activity in young women. Multiunit peroneal recordings
      of muscle sympathetic nerve activity were obtained in 17 women (mean+/-SEM: age
      24+/-3 years) and 21 men (mean+/-SEM: age 25+/-5 years). Mean resting muscle
      sympathetic nerve activity was lower in women compared with men (19+/-3 versus
      25+/-1 bursts minute(-1); P<0.05), as was mean arterial pressure (89+/-1 versus
      94+/-2 mm Hg; P<0.05). Mean arterial pressure was not related to muscle
      sympathetic nerve activity in men (P=0.80) or women (P=0.62). There was a
      positive relationship between total peripheral resistance and muscle sympathetic
      nerve activity (r=0.62; P<0.05) and an inverse relationship between cardiac
      output and muscle sympathetic nerve activity (r=-0.69; P<0.05) in men.
      Unexpectedly, muscle sympathetic nerve activity had no relationship to either
      total peripheral resistance (r=-0.27; P>0.05) or cardiac output (r=0.23; P>0.05)
      in women. Our results demonstrate that men and women rely on different integrated
      physiological mechanisms to maintain a normal arterial pressure despite widely
      varying sympathetic nerve activity among individuals. These findings may have
      important implications for understanding how hypertension and other disorders of
      blood pressure regulation occur in men and women.

PMID- 19171793
TI  - Energy metabolism in human renin-gene transgenic rats: does renin contribute to
      obesity?
AB  - Renin initiates angiotensin II formation and has no other known functions. We
      observed that transgenic rats (TGR) overexpressing the human renin gene (hREN)
      developed moderate obesity with increased body fat mass and glucose intolerance
      compared with nontransgenic Sprague-Dawley (SD) rats. The metabolic changes were
      not reversed by an angiotensin-converting enzyme inhibitor, a direct renin
      inhibitor, or by (pro)renin receptor blocker treatment. The obese phenotype in
      TGR(hREN) originated from higher food intake, which was partly compensated by
      increases in resting energy expenditure, total thermogenesis (postprandial and
      exercise activity), and lipid oxidation during the first 8 weeks of life. Once
      established, the difference in body weight between TGR(hREN) and SD rats remained
      constant over time. When restricted to the caloric intake of SD, TGR(hREN)
      developed an even lower body weight than nontransgenic controls. We did not
      observe significant changes in the cocaine and amphetamine-regulated transcript,
      pro-opiomelanocortin, both anorexigenic, or neuropeptide Y, orexigenic, mRNA
      levels in TGR(hREN) versus SD controls. However, the mRNA level of the agouti
      related peptide, orexigenic, was significantly reduced in TGR(hREN) versus SD
      controls at the end of the study, which indicates a compensatory mechanism. We
      suggest that the human renin transgene initiates a process leading to increased
      and early appetite, obesity, and metabolic changes not related to angiotensin II.
      The mechanisms are independent of any currently known renin-related effects.

PMID- 19171794
TI  - Heme oxygenase-1 induction remodels adipose tissue and improves insulin
      sensitivity in obesity-induced diabetic rats.
AB  - Obesity-associated inflammation causes insulin resistance. Obese adipose tissue
      displays hypertrophied adipocytes and increased expression of the cannabinoid-1
      receptor. Cobalt protoporphyrin (CoPP) increases heme oxygenase-1 (HO-1)
      activity, increasing adiponectin and reducing inflammatory cytokines. We
      hypothesize that CoPP administration to Zucker diabetic fat (ZDF) rats would
      improve insulin sensitivity and remodel adipose tissue. Twelve-week-old Zucker
      lean and ZDF rats were divided into 4 groups: Zucker lean, Zucker lean-CoPP, ZDF,
      and ZDF-CoPP. Control groups received vehicle and treatment groups received CoPP
      (2 mg/kg body weight) once weekly for 6 weeks. Serum insulin levels and glucose
      response to insulin injection were measured. At 18 weeks of age, rats were
      euthanized, and aorta, kidney, and subcutaneous and visceral adipose tissues were
      harvested. HO-1 expression was measured by Western blot analysis and HO-1
      activity by serum carbon monoxide content. Adipocyte size and cannabinoid-1
      expression were measured. Adipose tissue volumes were determined using MRI. CoPP
      significantly increased HO-1 activity, phosphorylated AKT and phosphorylated AMP
      kinase, and serum adiponectin in ZDF rats. HO-1 induction improved
      hyperinsulinemia and insulin sensitivity in ZDF rats. Subcutaneous and visceral
      adipose tissue volumes were significantly decreased in ZDF rats. Adipocyte size
      and cannabinoid-1 expression were both significantly reduced in ZDF-CoPP rats in
      subcutaneous and visceral adipose tissues. This study demonstrates that HO-1
      induction improves insulin sensitivity, downregulates the peripheral
      endocannabinoid system, reduces adipose tissue volume, and causes adipose tissue
      remodeling in a model of obesity-induced insulin resistance. These findings
      suggest HO-1 as a potential therapeutic target for obesity and its associated
      health risks.

PMID- 19171795
TI  - Mutations in three distinct loci cause resistance to peptide deformylase
      inhibitors in Bacillus subtilis.
AB  - Bacillus subtilis mutants with resistance against peptide deformylase inhibitors
      were isolated. All showed a bypass of the pathway through mutations in three
      genes required for formylation of Met-tRNA(fMet), fmt, folD, and glyA. glyA
      corresponds to a yet uncharacterized locus inducing resistance. The bypass of
      formylation caused robust fitness reduction but was not accompanied by
      alterations of the transcription profile. A subtle adaptation of the enzymes of
      the intermediary metabolism was observed.

PMID- 19171796
TI  - In vitro activities of retigeric acid B alone and in combination with azole
      antifungal agents against Candida albicans.
AB  - The vitro antifungal activity of retigeric acid B (RAB), a pentacyclic
      triterpenoid from the lichen species Lobaria kurokawae, was evaluated alone and
      in combination with fluconazole, ketoconazole, and itraconazole against Candida
      albicans using checkerboard microdilution and time-killing tests. The MICs for
      RAB against 10 different C. albicans isolates ranged from 8 to 16 microg/ml. A
      synergistic action of RAB and azole was observed in azole-resistant strains,
      whereas synergistic or indifferent effects were observed in azole-sensitive
      strains when interpreted by a separate approach of the fractional inhibitory
      concentration index and DeltaE model (the difference between the predicted and
      measured fungal growth percentages). In time-killing tests, we used both colony
      counts and a colorimetric assay to evaluate the combinational antifungal effects
      of RAB and azoles, which further confirmed their synergistic interactions. These
      findings suggest that the natural product RAB may play a certain role in
      increasing the susceptibilities of azole-resistant C. albicans strains.

PMID- 19171797
TI  - In vitro activity and preclinical profile of TMC435350, a potent hepatitis C
      virus protease inhibitor.
AB  - The hepatitis C virus (HCV) NS3/4A serine protease has been explored as a target
      for the inhibition of viral replication in preclinical models and in HCV-infected
      patients. TMC435350 is a highly specific and potent inhibitor of NS3/4A protease
      selected from a series of novel macrocyclic inhibitors. In biochemical assays
      using NS3/4A proteases of genotypes 1a and 1b, inhibition constants of 0.5 and
      0.4 nM, respectively, were determined. TMC435350 inhibited HCV replication in a
      cellular assay (subgenomic 1b replicon) with a half-maximal effective
      concentration (EC(50)) of 8 nM and a selectivity index of 5,875. The compound was
      synergistic with alpha interferon and an NS5B inhibitor in the replicon model and
      additive with ribavirin. In rats, TMC435350 was extensively distributed to the
      liver and intestinal tract (tissue/plasma area under the concentration-time curve
      ratios of >35), and the absolute bioavailability was 44% after a single oral
      administration. Compound concentrations detected in both plasma and liver at 8 h
      postdosing were above the EC(99) value measured in the replicon. In conclusion,
      given the selective and potent in vitro anti-HCV activity, the potential for
      combination with other anti-HCV agents, and the favorable pharmacokinetic
      profile, TMC435350 has been selected for clinical development.

PMID- 19171798
TI  - Detection of human immunodeficiency virus (HIV) type 1 M184V and K103N minority
      variants in patients with primary HIV infection.
AB  - We used an allele-specific real-time PCR assay to explore the presence of K103N
      and M184V minority species among primary human immunodeficiency virus (HIV)
      infections and their potential influence in HIV transmission. Thirty randomly
      chosen antiretroviral drug-naive patients lacking both the K103N and the M184V
      mutations as determined by conventional sequencing methods were studied, and
      K103N and M184V viral minority species were found in three (10%) and four (11%)
      patients, respectively.

PMID- 19171800
TI  - Accelerated metabolism of voriconazole and its partial reversal by cimetidine.
AB  - We report a case of accelerated metabolism of voriconazole during therapy for
      invasive pulmonary aspergillosis, resulting in subtherapeutic levels. Target
      voriconazole levels were restored with high dosages of voriconazole (up to 40
      mg/kg of body weight/day) and the addition of cimetidine as a cytochrome P450
      enzyme inhibitor.

PMID- 19171799
TI  - A novel gene, erm(41), confers inducible macrolide resistance to clinical
      isolates of Mycobacterium abscessus but is absent from Mycobacterium chelonae.
AB  - Mycobacterium abscessus infections tend to respond poorly to macrolide-based
      chemotherapy, even though the organisms appear to be susceptible to
      clarithromycin. Circumstantial evidence suggested that at least some M. abscessus
      isolates might be inducibly resistant to macrolides. Thus, the purpose of this
      study was to investigate the macrolide phenotype of M. abscessus clinical
      isolates. Inducible resistance to clarithromycin (MIC > 32 microg/ml) was found
      for 7 of 10 clinical isolates of M. abscessus previously considered susceptible;
      the remaining 3 isolates were deemed to be susceptible (MIC <or= 0.5 microg/ml).
      Inducible resistance was conferred by a novel erm gene, erm(41), which was
      present in all 10 isolates and in an isolate of Mycobacterium bolletii (M.
      abscessus type II). However, the erm(41) alleles were nonfunctional in the three
      susceptible M. abscessus isolates. No evidence of erm(41) was found in
      Mycobacterium chelonae, and an isolate of Mycobacterium massiliense appeared to
      be an erm(41) deletion mutant. Expression of erm(41) in M. abscessus conferred
      resistance to clarithromycin and erythromycin and the ketolide HMR3004. However,
      this species was found to be intrinsically resistant, independent of erm(41), to
      clindamycin, quinupristin (streptogramin B), and telithromycin. The ability to
      confer resistance to clindamycin and telithromycin, but not quinupristin, was
      demonstrated by expressing erm(41) in Maycobacterium smegmatis. Exposure of M.
      abscessus to the macrolide-lincosamide-streptogramin B-ketolide agents increased
      the levels of erm(41) mRNA 23- to 250-fold within 24 h. The inducible macrolide
      resistance phenotype of some M. abscessus isolates may explain the lack of
      efficacy of macrolide-based chemotherapy against this organism.

PMID- 19171801
TI  - Activity of posaconazole and other antifungal agents against Mucorales strains
      identified by sequencing of internal transcribed spacers.
AB  - The antifungal susceptibility profiles of 77 clinical strains of Mucorales
      species, identified by internal transcribed spacer sequencing, were analyzed.
      MICs obtained at 24 and 48 h were compared. Amphotericin B was the most active
      agent against all isolates, except for Cunninghamella and Apophysomyces isolates.
      Posaconazole also showed good activity for all species but Cunninghamella
      bertholletiae. Voriconazole had no activity against any of the fungi tested.
      Terbinafine showed good activity, except for Rhizopus oryzae, Mucor
      circinelloides, and Rhizomucor variabilis isolates.

PMID- 19171802
TI  - Synthesis and antimalarial activities of cyclen 4-aminoquinoline analogs.
AB  - In an attempt to augment the efficacy of 7-chloro 4-aminoquinoline analogs and
      also to overcome resistance to antimalarial agents, we synthesized three cyclen
      (1,4,7,10-tetraazacyclododecane) analogs of chloroquine [a bisquinoline
      derivative, 7-chloro-4-(1,4,7,10-tetraaza-cyclododec-1-yl)-quinoline HBr, and a 7
      chloro-4-(1,4,7,10-tetraaza-cyclododec-1-yl)-quinoline-Zn(2+) complex]. The
      bisquinoline displays the most potent in vitro and in vivo antimalarial
      activities. It displays 50% inhibitory concentrations (IC(50)s) of 7.5 nM against
      the D6 (chloroquine-sensitive) clone of Plasmodium falciparum and 19.2 nM against
      the W2 (chloroquine-resistant) clone, which are comparable to those of
      artemisinin (10.6 and 5.0 nM, respectively) and lower than those of chloroquine
      (10.7 and 87.2 nM, respectively), without any evidence of cytotoxicity to
      mammalian cells, indicating a high selectivity index (>1,333 against D6 clone and
      >521 against W2 clone). Potent antimalarial activities of the bisquinoline
      against chloroquine- and mefloquine-resistant strains of P. falciparum were also
      confirmed by in vitro [(3)H]hypoxanthine incorporation assay. The in vivo
      antimalarial activity of the bisquinoline, as determined in P. berghei-infected
      mice, is comparable to that of chloroquine (50% effective dose, <or=1.1 mg/kg
      when given orally); no apparent toxicity has been observed up to the highest dose
      tested (3 x 30 mg/kg). The bisquinoline inhibits in vitro hemozoin (beta-hematin)
      formation with an IC(50) of 1.1 microM, which is about 10-fold more potent than
      chloroquine (IC(50) 9.5 microM). Overall, this article describes the discovery of
      a new class of cyclen 4-aminoquinoline analogs as potent antimalarial drugs.

PMID- 19171803
TI  - Relationship between susceptibility to daptomycin in vitro and activity in vivo
      in a rabbit model of aortic valve endocarditis.
AB  - Daptomycin is approved for treatment of Staphylococcus aureus bacteremia and
      right-sided endocarditis. Increases in daptomycin MICs have been associated with
      failure. A rabbit model of aortic valve endocarditis was used to determine
      whether MIC correlates with activity in vivo and whether a higher daptomycin dose
      can improve efficacy. Two related clinical S. aureus strains, one with a
      daptomycin MIC of 0.5 microg/ml and the other with a MIC of 2 microg/ml, were
      used to establish aortic valve endocarditis in rabbits. Daptomycin was
      administered once a day for 4 days at 12 mg/kg of body weight or 18 mg/kg to
      simulate doses in humans of 6 mg/kg and 10 mg/kg, respectively. Endocardial
      vegetations, spleens, and kidneys were harvested and quantitatively cultured. The
      strain with a MIC of 2 microg/ml had a survival advantage over the strain with a
      MIC of 0.5 microg/ml with >100 times more organisms of the former in endocardial
      vegetations at the 12-mg/kg dose in a dual-infection model. Both the 12-mg/kg
      dose and the 18-mg/kg dose completely eradicated the strain with a MIC of 0.5
      from vegetations, spleens, and kidneys. The 12-mg/kg dose was ineffective against
      the strain with a MIC of 2 in vegetations; the 18-mg/kg dose produced a reduction
      of 3 log(10) units in CFU in vegetations compared to the controls, although in no
      rabbit were organisms completely eliminated. Increasing the dose of daptomycin
      may improve its efficacy for infections caused by strains with reduced daptomycin
      susceptibility.

PMID- 19171804
TI  - The effects of health information technology on inpatient care.

PMID- 19171805
TI  - Clinical information technologies and inpatient outcomes: a multiple hospital
      study.
AB  - BACKGROUND: Despite speculation that clinical information technologies will
      improve clinical and financial outcomes, few studies have examined this
      relationship in a large number of hospitals. METHODS: We conducted a cross
      sectional study of urban hospitals in Texas using the Clinical Information
      Technology Assessment Tool, which measures a hospital's level of automation based
      on physician interactions with the information system. After adjustment for
      potential confounders, we examined whether greater automation of hospital
      information was associated with reduced rates of inpatient mortality,
      complications, costs, and length of stay for 167 233 patients older than 50 years
      admitted to responding hospitals between December 1, 2005, and May 30, 2006.
      RESULTS: We received a sufficient number of responses from 41 of 72 hospitals
      (58%). For all medical conditions studied, a 10-point increase in the automation
      of notes and records was associated with a 15% decrease in the adjusted odds of
      fatal hospitalizations (0.85; 95% confidence interval, 0.74-0.97). Higher scores
      in order entry were associated with 9% and 55% decreases in the adjusted odds of
      death for myocardial infarction and coronary artery bypass graft procedures,
      respectively. For all causes of hospitalization, higher scores in decision
      support were associated with a 16% decrease in the adjusted odds of complications
      (0.84; 95% confidence interval, 0.79-0.90). Higher scores on test results, order
      entry, and decision support were associated with lower costs for all hospital
      admissions (-$110, -$132, and -$538, respectively; P < .05). CONCLUSION:
      Hospitals with automated notes and records, order entry, and clinical decision
      support had fewer complications, lower mortality rates, and lower costs.

PMID- 19171808
TI  - Effects of exercise modality on insulin resistance and functional limitation in
      older adults: a randomized controlled trial.
AB  - BACKGROUND: Authorities advocate that resistance and aerobic exercise are
      essential for reducing risk factors for chronic disease and disability in older
      adults. However, the incremental effects of combined resistance and aerobic
      exercise compared with either modality alone on risk factors for disease and
      disability is generally unknown. METHODS: Participants were 136 sedentary,
      abdominally obese older men and women recruited from September 30, 2002, through
      November 15, 2006, at Queen's University. Participants were randomized to 1 of
      the following 4 groups for 6 months: resistance exercise, aerobic exercise,
      resistance and aerobic exercise (combined exercise), or nonexercise control.
      Primary outcomes were analyzed by an intent-to-treat model and included changes
      in insulin resistance by hyperinsulinemic-euglycemic clamp and functional
      limitation using the average change in 4 tests combined (average z score).
      RESULTS: After controlling for age, sex, and baseline value, insulin resistance
      improved compared with controls in the aerobic exercise and the combined exercise
      groups but not in the resistance exercise group. Improvement (mean [SE]) in the
      combined exercise group was greater than in the resistance exercise group (9.2
      [1.3] vs 1.8 [1.3] mg/mL/microIU per kilogram of skeletal muscle per minute x100
      [P < .001]) but not in the aerobic exercise group (9.2 [1.3] vs 6.5 [1.3]
      mg/mL/microIU per kilogram of skeletal muscle per minute x100 [P = .46]).
      Functional limitation improved significantly in all groups compared with the
      control group. Improvement in the combined exercise group was greater than in the
      aerobic exercise group (0.5 [0.1] vs -0.0 [0.1]; standard units, z score [P =
      .003]) but not in the resistance exercise group. Improvement in the resistance
      exercise group was not different from the aerobic exercise group. CONCLUSION: The
      combination of resistance and aerobic exercise was the optimal exercise strategy
      for simultaneous reduction in insulin resistance and functional limitation in
      previously sedentary, abdominally obese older adults. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00520858.

PMID- 19171806
TI  - Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and
      risk of breast cancer among premenopausal women in the Nurses' Health Study II.
AB  - BACKGROUND: The use of aspirin and other nonsteroidal anti-inflammatory drugs
      (NSAIDs) is widespread for treatment of common symptoms such as headaches,
      muscular pain, and inflammation. In addition, the chemopreventive use of NSAIDs
      is increasingly common for heart disease and colon cancer. Evidence of a
      protective association with breast cancer risk has been inconsistent, and few
      data exist for premenopausal women. METHODS: We assessed the associations for use
      of aspirin, other NSAIDs, and acetaminophen with breast cancer risk among
      premenopausal women in the prospective Nurses' Health Study II. In total, 112,292
      women, aged 25 to 42 years and free of cancer in 1989, were followed up until
      June 2003. Multivariate relative risks and 95% confidence intervals were
      calculated by Cox proportional hazards models, adjusting for age and other
      important breast cancer risk factors. RESULTS: Overall, 1345 cases of invasive
      premenopausal breast cancer were documented. Regular use of aspirin (> or = 2
      times per week) was not significantly associated with breast cancer risk
      (relative risk, 1.07; 95% confidence interval, 0.89-1.29). Regular use of either
      nonaspirin NSAIDs or acetaminophen also was not consistently associated with
      breast cancer risk. Results did not vary by frequency (days per week), dose
      (tablets per week), or duration of use. Furthermore, associations with each drug
      category did not vary substantially by estrogen and progesterone receptor status
      of the tumor. CONCLUSION: These data suggest that the use of aspirin, other
      NSAIDs, and acetaminophen is not associated with a reduced risk of breast cancer
      among premenopausal women.

PMID- 19171809
TI  - Loop diuretic use and fracture in postmenopausal women: findings from the Women's
      Health Initiative.
AB  - BACKGROUND: The relationship of loop diuretics to bone mineral density (BMD),
      falls, and fractures in postmenopausal women has not been established. METHODS:
      We examined whether loop diuretics are associated with changes in BMD, falls, and
      fractures in women enrolled in the Women's Health Initiative. We included the
      133,855 women (3411 users and 130,444 nonusers of loop diuretics) who were
      enrolled in the WHI from October 29, 1993 to December 31, 1998 and determined
      incident falls and fractures for a mean of 7.7 years. Women who had BMD
      measurements at baseline and at year 3 (300 users and 9124 nonusers of loop
      diuretics) were also examined. RESULTS: After adjustment for covariates, no
      significant association was found between ever use of loop diuretics and total
      (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.00-1.19), hip (HR,
      1.21; 95% CI, 0.91-1.60), and clinical vertebral fractures (HR, 1.17; 95% CI,
      0.92-1.48) and falls (1.02; 0.96-1.08). An increased risk was found for other
      clinical fractures (1.16; 1.01-133) and total fractures (1.16; 1.03-1.31) with
      more than 3 years' use of loop diuretics. The BMD changes were not associated
      with loop diuretic use. CONCLUSIONS: After adjustment for confounding variables,
      no significant association was found between ever use of loop diuretics and
      changes in BMD, falls, and fractures. Loop diuretics were used by women in poor
      health who were already at risk for fractures. However, prolonged use of loop
      diuretics was associated with higher fracture risk in postmenopausal women.

PMID- 19171810
TI  - Increased mortality and cardiovascular morbidity associated with use of
      nonsteroidal anti-inflammatory drugs in chronic heart failure.
AB  - BACKGROUND: Accumulating evidence indicates increased cardiovascular risk
      associated with nonsteroidal anti-inflammatory drug (NSAID) use, in particular in
      patients with established cardiovascular disease. We studied the risk of death
      and hospitalization because of acute myocardial infarction and heart failure (HF)
      associated with use of NSAIDs in an unselected cohort of patients with HF.
      METHODS: We identified 107,092 patients surviving their first hospitalization
      because of HF between January 1, 1995, and December 31, 2004, and their
      subsequent use of NSAIDs from individual-level linkage of nationwide registries
      of hospitalization and drug dispensing by pharmacies in Denmark. Data analysis
      was performed using Cox proportional hazard models adjusted for age, sex,
      calendar year, comorbidity, medical treatment, and severity of disease, and
      propensity-based risk-stratified models and case-crossover models. RESULTS: A
      total of 36,354 patients (33.9%) claimed at least 1 prescription of an NSAID
      after discharge; 60,974 (56.9%) died, and 8970 (8.4%) and 39,984 (37.5%) were
      hospitalized with myocardial infarction or HF, respectively. The hazard ratio
      (95% confidence interval) for death was 1.70 (1.58-1.82), 1.75 (1.63-1.88), 1.31
      (1.25-1.37), 2.08 (1.95-2.21), 1.22 (1.07-1.39), and 1.28 (1.21-1.35) for
      rofecoxib, celecoxib, ibuprofen, diclofenac, naproxen, and other NSAIDs,
      respectively. Furthermore, there was a dose-dependent increase in risk of death
      and increased risk of hospitalization because of myocardial infarction and HF.
      Propensity-based risk-stratified analysis and case-crossover models yielded
      similar results. CONCLUSIONS: NSAIDs are frequently used in patients with HF and
      are associated with increased risk of death and cardiovascular morbidity.
      Inasmuch as even commonly used NSAIDs exerted increased risk, the balance between
      risk and benefit requires careful consideration when any NSAID is given to
      patients with HF.

PMID- 19171811
TI  - The ACCORD Trial and control of blood glucose level in type 2 diabetes mellitus:
      time to challenge conventional wisdom.

PMID- 19171812
TI  - Uric acid and insulin sensitivity and risk of incident hypertension.
AB  - BACKGROUND: Uric acid, insulin sensitivity, and endothelial dysfunction may be
      important in the development of hypertension. Corresponding circulating
      biomarkers are associated with risk of hypertension, but because these factors
      may be interrelated, whether they independently affect risk is unknown. METHODS:
      In 1496 women aged 32 to 52 years without hypertension at baseline, we
      prospectively analyzed the associations between fasting plasma levels of uric
      acid, insulin, triglycerides, the insulin sensitivity index, and 2 biomarkers
      associated with endothelial dysfunction (homocysteine and soluble intercellular
      adhesion molecule-1) and the odds of incident hypertension. Odds ratios were
      adjusted for standard risk factors and then for all biomarkers plus estimated
      glomerular filtration rate and total cholesterol level. Population-attributable
      risk was estimated for biomarkers significantly associated with hypertension.
      RESULTS: All the biomarkers were associated with incident hypertension after
      adjustment for standard hypertension risk factors. However, after simultaneously
      controlling for all the biomarkers, estimated glomerular filtration rate, and
      total cholesterol level, only uric acid and insulin levels were independently
      associated with incident hypertension. Comparing the highest and lowest quartiles
      of uric acid levels, the odds ratio was 1.89 (95% confidence interval, 1.26
      2.82). A similar comparison yielded an odds ratio of 2.03 (95% confidence
      interval, 1.35-3.05) for insulin levels. Using an estimated basal incidence rate
      of 14.6 per 1000 annually, 30.8% of all hypertension occurring in young women
      annually is associated with uric acid levels of 3.4 mg/dL or greater (to convert
      to micromoles per liter, multiply by 59.485). For insulin levels of 2.9
      microIU/mL or greater (to convert to picomoles per liter, multiply by 6.945),
      this proportion is 24.2%. CONCLUSIONS: Differences in uric acid and insulin
      levels robustly and substantially affect the risk of hypertension in young women.
      Measuring these biomarkers in clinical practice may identify higher-risk
      individuals.

PMID- 19171814
TI  - Exclusive Staphylococcus aureus throat carriage: at-risk populations.
AB  - BACKGROUND: Approximately 25% of Staphylococcus aureus carriers have exclusive
      throat carriage. We aimed to identify the populations at risk for exclusive
      throat carriage to improve sensitivity to detect carriers. METHODS: Four groups
      underwent nasal and throat screening for S. aureus. Three groups of individuals
      in the community (n = 2632) with different estimated levels of exposure to the
      health care system (HCS) were screened, including 1500 healthy blood donors, 498
      patients from a school of dental medicine, and 634 health care workers (HCWs) at
      a trade fair. The fourth group comprised in-hospital patients and HCWs (n = 832)
      and was considered the group with the highest estimated exposure to the HCS. As a
      primary outcome, we analyzed risk factors for exclusive throat carriage in
      exclusive throat carriers vs all nasal carriers. RESULTS: Of 3464 individuals
      screened, 428 (12.4%) had exclusive throat carriage, and 1260 (36.4%) had
      carriage in the nares only or in the nares and the throat. The most important
      independent risk factor for exclusive throat carriage was age 30 years or younger
      (odds ratio, 1.66; P < .001). Exposure to the HCS was a significant protective
      factor for exclusive throat carriage (odds ratio, 0.67; P = .001). Healthy blood
      donors were almost twice as likely to have exclusive throat carriage than in
      hospital patients and HCWs (30.2% vs 18.4% of all carriers, P < .001).
      CONCLUSIONS: Absence of exposure to the HCS and younger age predicted exclusive
      throat carriers, a population at high risk for community-onset methicillin
      resistant S. aureus. Screening for S. aureus should include swabs from the
      anterior nares and from the throat to improve the likelihood of detecting
      carriers.

PMID- 19171815
TI  - Cost-effectiveness of interferon gamma release assays vs tuberculin skin tests in
      health care workers.
AB  - BACKGROUND: Interferon gamma release assays (IGRAs) offer alternatives to
      tuberculin skin tests (TSTs) for diagnosing latent tuberculosis infection (LTBI).
      Unlike TSTs, IGRAs require only a single patient visit and are not affected by
      prior BCG vaccination, providing greater specificity. Of 2 Food and Drug
      Administration-approved IGRAs, the newer QuantiFERON-TB Gold in Tube test (QFT
      GIT) requires less manual processing time than the QuantiFERON-TB Gold test (QFT
      G). We compared the cost-effectiveness of the QFT-G, QFT-GIT, and TST for
      detecting LTBI in new health care workers (HCWs). METHODS: A Markov state
      transition decision analytic model using the societal perspective and lifetime
      horizon was constructed to compare costs and quality-adjusted life-years (QALYs)
      associated with the 3 strategies for hypothetical 35-year-old HCWs with or
      without prior BCG vaccination. Direct and indirect costs and probabilities were
      based on manufacturer data, national Veterans Health Administration records, and
      the published literature. Future costs and QALYs were discounted at 3% per year.
      RESULTS: Both IGRAs were more effective and less costly than the TST, whether or
      not the HCW had been vaccinated with BCG previously. The incremental cost
      effectiveness ratio of the QFT-G compared with the QFT-GIT was $14,092/QALY for
      non-BCG-vaccinated HCWs and $103,047/QALY for BCG-vaccinated HCWs. There was no
      prevalence of LTBI at which the TST became the most effective or least costly
      strategy. If the sensitivity of the QFT-GIT exceeds that of the QFT-G, then the
      QFT-GIT is the most effective and least costly strategy. CONCLUSION: Use of the
      QFT-G and QFT-GIT leads to superior clinical outcomes and lower costs than the
      TST and should be considered in screening non-BCG-vaccinated and BCG-vaccinated
      new HCWs for LTBI.

PMID- 19171816
TI  - Tuberculosis and substance abuse in the United States, 1997-2006.
AB  - BACKGROUND: Tuberculosis (TB) control efforts are often ineffective in
      controlling TB among patients who use illicit drugs or abuse alcohol (substance
      abuse). This study examined the prevalence of substance abuse among TB cases
      reported in the United States and assessed the relation between substance abuse
      and indicators of TB transmission. METHODS: A cross-sectional analysis was
      performed of data on US TB cases in patients 15 years or older reported from 1997
      through 2006. Analyses included number and proportion of patients with TB
      characterized by substance abuse and associations between substance abuse, sputum
      smear status, treatment failure, and inclusion in a county-level genotype
      cluster. RESULTS: Of 153,268 patients with TB, 28,650 (18.7%) reported substance
      abuse, including 22,293 of 76,816 US-born patients (29.0%). Multivariate analysis
      showed that, among patients negative for human immunodeficiency virus, odds of
      sputum smear-positive disease were 1.8 (99% confidence interval [CI], 1.7-1.9)
      times greater among those who reported substance abuse; this association was
      weaker among patients with human immunodeficiency virus infection (odds ratio
      [OR], 1.2; 99% CI, 1.1-1.4). Among female patients, odds of treatment failure
      were 2.4 (99% CI, 1.9-3.0) times greater among those who reported substance
      abuse. The association was weaker among male patients (OR, 1.5; 99% CI, 1.3-1.7).
      Patients who abused substances were more likely to be involved in a county-level
      genotype cluster (US-born: OR, 2.3; 99% CI, 2.0-2.7; foreign-born: 1.5; 1.2-2.0).
      CONCLUSIONS: Substance abuse is the most commonly reported behavioral risk factor
      among patients with TB in the United States. Patients who abuse substances are
      more contagious (eg, smear positive) and remain contagious longer because
      treatment failure presumably extends periods of infectiousness. Increased
      transmission is consistent with our finding that patients who abuse substances
      were more likely to be involved in a localized genotype cluster, which can
      represent recent transmission.

PMID- 19171817
TI  - Ability of hospitalized patients to identify their in-hospital physicians.

PMID- 19171818
TI  - A novel therapy for lymphedema.

PMID- 19171819
TI  - Physician influences on patient care: random vs fixed effects.

PMID- 19171820
TI  - Racial disparities in diabetes and physicians: lack of association does not
      indicate cause or cure.

PMID- 19171813
TI  - Impact of a weight management program on health-related quality of life in
      overweight adults with type 2 diabetes.
AB  - BACKGROUND: Inconsistent findings have been reported regarding improved health
      related quality of life (HRQOL) after weight loss. We tested the efficacy of a
      weight management program for improving HRQOL in overweight or obese adults
      diagnosed as having type 2 diabetes mellitus. METHODS: We conducted a randomized
      multisite clinical trial at 16 outpatient research centers with 2 treatment arms
      and blinded measurements at baseline and the end of year 1. A total of 5145
      participants (mean [SD] age, 58.7 [6.9] years; mean [SD] body mass index
      [calculated as weight in kilograms divided by height in meters squared], 36.0
      [5.9]; 59.5% women; 63.1% white) were randomized to an intensive lifestyle
      intervention (ILI) or to diabetes support and education (DSE). Main outcome
      measures included the 36-Item Short-Form Health Survey physical component summary
      (PCS) and mental health component summary (MCS) scores and Beck Depression
      Inventory II (BDI-II) scores. Baseline mean (SD) scores were 47.9 (7.9) for PCS,
      54.0 (8.1) for MCS, and 5.7 (5.0) for BDI-II. RESULTS: Improved HRQOL was
      demonstrated by the PCS and BDI-II scores (P < .001) in the ILI arm compared with
      the DSE arm. The largest effect was observed for the PCS score (difference, 
      2.91; 99% confidence interval, -3.44 to -2.37). The greatest HRQOL improvement
      occurred in participants with the lowest baseline HRQOL levels. Mean (SD) changes
      in weight (ILI, -8.77 [8.2] kg and DSE, -0.86 [5.0] kg), improved fitness, and
      improved physical symptoms mediated treatment effects associated with the BDI-II
      and PCS. CONCLUSIONS: Overweight adults diagnosed as having type 2 diabetes
      experienced significant improvement in HRQOL by enrolling in a weight management
      program that yielded significant weight loss, improved physical fitness, and
      reduced physical symptoms. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00017953.

PMID- 19171821
TI  - Tailoring internal medicine training to improve hospitalist outcomes.

PMID- 19171822
TI  - Hospitalist care.

PMID- 19171823
TI  - Education research: neurology residency training in the new millennium.
AB  - OBJECTIVE: To survey adult neurology program directors (ANPD) to identify their
      most pressing needs at a time of dramatic change in neurology resident education.
      METHODS: All US ANPD were surveyed in 2007 using an instrument adjusted from a
      1999 survey instrument. The goal was to characterize current program content, the
      institution and evaluation of the core competencies, program director
      characteristics, program director support, the institution of work duty hour
      requirements, resident support, and the curriculum needs of program directors and
      programs. RESULTS: A response rate of 82.9% was obtained. There is a significant
      disconnect between administration time spent by ANPD and
      departmental/institutional support of this, with ANPD spending approximately 35%
      of a 50-hour week on administration with only 16.7% salary support. Rearrangement
      of rotations or services has been the most common mode for ANPD to deal with work
      duty hour requirements, with few programs employing mid level providers. Most
      ANPD do not feel work duty hour reform has improved resident education. More
      residents are entering fellowships following graduation than documented in the
      past. Curriculum deficiencies still exist for ANPD to meet all Neurology Program
      Requirements, especially for nontraditional neurology topics outside the
      conventional bounds of clinical neurology (e.g., practice management). Nearly one
      quarter of neurology residency programs do not have a meeting or book fund for
      every resident in the program. CONCLUSIONS: Adult neurology program directors
      (ANPDs) face multiple important financial and organizational hurdles. At a time
      of increasing complexity in medical education, ANPDs need more institutional
      support.

PMID- 19171824
TI  - Alzheimer disease: what changes in the brain cause dementia?

PMID- 19171826
TI  - ACGME, test thyself!

PMID- 19171827
TI  - Effect of aerobic training in patients with spinal and bulbar muscular atrophy
      (Kennedy disease).
AB  - OBJECTIVE: We examined the effect of aerobic exercise in patients with spinal and
      bulbar muscular atrophy (SBMA). SBMA is caused by a defect androgen receptor.
      This defect causes motor neuron death, but considering the important function of
      androgens in muscle, it is possible that muscle damage in SBMA also occurs
      independently of motor neuron damage. METHODS: Eight patients with SBMA engaged
      in regular cycling exercise for 12 weeks. Maximum oxygen uptake (Vo(2max)),
      maximal work capacity (W(max)), muscle morphology, citrate synthase (CS)
      activity, body composition, EMG, static strength measurements, lung function,
      plasma proteins, and hormones were evaluated before and after training.
      Evaluation of improvements in activities of daily living (ADL) was conducted
      after training. RESULTS: W(max) increased by 18%, and CS activity increased by
      35%. There was no significant change in Vo(2max) or any of the other variables
      examined before and after training, and the patients with SBMA did not feel
      improvements in ADL. CONCLUSIONS: Frequent, moderate-intensity aerobic
      conditioning is of little beneficial effect in patients with spinal and bulbar
      muscular atrophy (SBMA). High levels of plasma creatine kinase and muscle
      regeneration indicate a primary myopathic affection, which, in parallel with the
      motor neuron deficiency, may attenuate the response to exercise training in
      patients with SBMA.

PMID- 19171828
TI  - Comparing explorative saccade and flicker training in hemianopia: a randomized
      controlled study.
AB  - OBJECTIVE: Patients with homonymous hemianopia are disabled on everyday
      exploratory activities. We examined whether explorative saccade training (EST),
      compared with flicker-stimulation training (FT), would selectively improve
      saccadic behavior on the patients' blind side and benefit performance on natural
      exploratory tasks. METHODS: Twenty-eight hemianopic patients were randomly
      assigned to distinct groups performing for 6 weeks either EST (a digit-search
      task) or FT (blind-hemifield stimulation by flickering letters). Outcome
      variables (response times [RTs] during natural search, number of fixations during
      natural scene exploration, fixation stability, visual fields, and quality-of-life
      scores) were collected before, directly after, and 6 weeks after training.
      RESULTS: EST yielded a reduced (post/pre, 47%) digit-search RT for the blind
      side. Natural search RT decreased (post/pre, 23%) on the blind side but not on
      the seeing side. After FT, both sides' RT remained unchanged. Only with EST did
      the number of fixations during natural scene exploration increase toward the
      blind and decrease on the seeing side (follow-up/pre difference, 238%). Even with
      the target located on the seeing side, after EST more fixations occurred toward
      the blind side. The EST group showed decreased (post/pre, 43%) fixation stability
      and increased (post/pre, 482%) asymmetry of fixations toward the blind side.
      Visual field size remained constant after both treatments. EST patients reported
      improvements in social domain. CONCLUSIONS: Explorative saccade training
      selectively improves saccadic behavior, natural search, and scene exploration on
      the blind side. Flicker-stimulation training does not improve saccadic behavior
      or visual fields. The findings show substantial benefits of compensatory
      exploration training, including subjective improvements in mastering daily-life
      activities, in a randomized controlled trial.

PMID- 19171829
TI  - TP53 codon 72 polymorphism is associated with age at onset of glioblastoma.
AB  - BACKGROUND: Functional single nucleotide polymorphisms (SNP) in codon 72 of TP53
      have been shown to be a risk factor, a prognostic marker, and related factor to
      age at onset in various cancers. METHODS: We investigated blood samples from 254
      patients with glioblastoma and 238 healthy controls. RESULTS: TP53 codon 72
      status was not correlated with prognosis and did not differ between glioblastoma
      and control populations. However, the Pro/Pro genotype was overrepresented in
      patients <45 years (20.6% vs 6.4% in patients with glioblastoma >45 years, p =
      0.002, vs 5.9% in control group, p = 0.001). We then confirmed this result on an
      independent series of young patients with glioblastoma. Finally, the analysis of
      tumor DNA found the Pro allele associated with occurrence of TP53 somatic
      mutation. CONCLUSION: Our data suggest that TP53 functional variation is
      particularly critical for oncogenesis of glioblastoma in young patients.

PMID- 19171830
TI  - Treatment of CNS sarcoidosis with infliximab and mycophenolate mofetil.
AB  - OBJECTIVE: To describe the effects of the anti-tumor necrosis factor neutralizing
      antibody, infliximab, and the antiproliferative immunosuppressant, mycophenolate
      mofetil, in refractory neurosarcoidosis. METHODS: We treated patients with biopsy
      proven sarcoidosis and CNS involvement, who had failed treatment with steroids,
      with infliximab (5 mg/kg on weeks 0, 2, and 6, and then every 6-8 weeks
      thereafter). Six out of seven patients were co-treated with mycophenolate mofetil
      (1,000 mg PO BID). Patients underwent a review of symptoms and complete
      neurologic examination every 3 months and MRI scanning before and after 3-4
      infusions of infliximab. RESULTS: All patients reported significant symptomatic
      improvement by the fourth infusion of infliximab, including relief of headache
      and neuropathic pain, reversal of motor, sensory, or coordination deficits, and
      control of seizure activity. Furthermore, infliximab therapy was universally
      associated with a decrease in lesion size or suppression of gadolinium
      enhancement as documented by MRI. A positive treatment response was attained
      irrespective of location or distribution of CNS involvement by sarcoidosis
      (dural/leptomeningeal based vs intraparenchymal; cord vs brain; single lesion vs
      multifocal). There were no serious adverse effects in a follow-up period spanning
      6-18 months. CONCLUSIONS: Combination treatment with mycophenolate mofetil and
      infliximab is a promising therapeutic approach for neurosarcoidosis.

PMID- 19171831
TI  - Treatment of intractable chronic cluster headache by occipital nerve stimulation
      in 14 patients.
AB  - BACKGROUND: Cluster headache is a primary headache involving repeated attacks of
      excruciatingly severe headache usually occurring several times a day. Most
      patients with chronic cluster headache (CCH) have an unremitting illness
      requiring daily preventive therapy for years. OBJECTIVE: To describe the clinical
      outcome of occipital nerve stimulation (ONS) for 14 patients with intractable
      CCH. METHODS: Fourteen patients with medically intractable CCH were implanted
      with bilateral electrodes in the suboccipital region for ONS and a retrospective
      assessment of their clinical outcome obtained. RESULTS: At a median follow-up of
      17.5 months (range 4-35 months), 10 of 14 patients reported improvement and 9 of
      these recommend ONS. Three patients noticed a marked improvement of 90% or better
      (90%, 90%, and 95%), 3 a moderate improvement of 40% or better (40%, 50%, and
      60%), and 4 a mild improvement of 20-30% (20%, 20%, 25%, and 30%). Improvement
      occurred within days to weeks for those who responded most and patients
      consistently reported their attacks returned within hours to days when the device
      was off. One patient found that ONS helped abort acute attacks. Adverse events of
      concern were lead migrations and battery depletion. CONCLUSION: Intractable
      chronic cluster headache (CCH) is a devastating, disabling condition that has
      traditionally been treated with cranially invasive or neurally destructive
      procedures. ONS offers a safe, effective option for some patients with CCH. More
      work is required to evaluate and understand this novel therapy.

PMID- 19171832
TI  - Epidemiology of ischemic stroke from atrial fibrillation in Dijon, France, from
      1985 to 2006.
AB  - BACKGROUND: Atrial fibrillation (AF) is strongly associated with age, and
      epidemiologic studies are needed to evaluate the impact of both aging of the
      population and the use of anticoagulant therapy in patients with AF on the
      incidence of cardioembolic stroke with AF (CE/AF stroke). METHODS: We evaluated
      trends in incidence rates, risk factors, prestroke therapy, and survival in CE/AF
      stroke from a prospective population-based registry, from 1985 to 2006. RESULTS:
      A total of 3,064 ischemic strokes, including 572 (18.7%) CE/AF strokes, were
      recorded. Over the 22 years, a decrease in the incidence of overall CE/AF stroke
      was noted (incidence rate ratio 0.9858, 95% confidence interval [CI] 0.9731
      0.9986; p = 0.03). We observed a higher prevalence of previous AF, previous
      myocardial infarction, and patients aged >70 years in CE/AF stroke (p < 0.0001)
      whereas hypercholesterolemia was more prevalent in other ischemic strokes (p =
      0.003). A significant increase in the use of anticoagulants and antiplatelet
      agents was noted, and was particularly pronounced for CE/AF stroke with previous
      AF. For CE/AF stroke, survival rates were 72% at 1 month (95% CI 0.68-0.76), 52%
      at 1 year (95% CI 0.48-0.56), and 43% at 2 years (95% CI 0.39-0.48), and remained
      lower than those of other ischemic stroke. CONCLUSIONS: The decrease in the
      incidence of cardioembolic/atrial fibrillation stroke in our study was probably
      due to a slight increase in the utilization of antithrombotic therapy in patients
      with atrial fibrillation, but the use of such therapies will have to increase
      further because of the expected aging of the population in coming years.

PMID- 19171833
TI  - Factors associated with resistance to dementia despite high Alzheimer disease
      pathology.
AB  - BACKGROUND: Autopsy series have shown that some elderly people remain with normal
      cognitive function during life despite having high burdens of pathologic lesions
      associated with Alzheimer disease (AD) at death. Understanding why these
      individuals show no cognitive decline, despite high AD pathologic burdens, may be
      key to discovery of neuroprotective mechanisms. METHODS: A total of 36 subjects
      who on autopsy had Braak stage V or VI and moderate or frequent neuritic plaque
      scores based on Consortium to Establish a Registry for Alzheimer's Disease
      (CERAD) standards were included. Twelve had normal cognitive function and 24 a
      diagnosis of AD before death. Demographic characteristics, clinical and
      pathologic data, as well as antemortem brain volumes were compared between the
      groups. RESULTS: In multiple regression analysis, antemortem hippocampal and
      total brain volumes were significantly larger in the group with normal cognitive
      function after adjusting for gender, age at MRI, time from MRI to death, Braak
      stage, CERAD neuritic plaque score, and overall presence of vascular disease.
      CONCLUSION: Larger brain and hippocampal volumes were associated with preserved
      cognitive function during life despite a high burden of Alzheimer disease (AD)
      pathologic lesions at death. A better understanding of processes that lead to
      preservation of brain volume may provide important clues for the discovery of
      mechanisms that protect the elderly from AD.

PMID- 19171834
TI  - Biochemical indicators of vitamin B12 and folate insufficiency and cognitive
      decline.
AB  - BACKGROUND: In some prospective studies, associations of serum vitamin B(12) and
      homocysteine concentrations with cognitive decline have been reported but few
      have examined the role of methylmalonic acid, a more specific marker of vitamin
      B(12) deficiency than homocysteine. OBJECTIVE: The aim of the study was to
      determine whether serum concentrations of vitamin B(12) or selected metabolites
      are related to cognitive decline. METHODS: A total of 516 subjects were selected
      in a stratified random sampling design from among Chicago Health and Aging
      Project participants for clinical evaluation. We used linear mixed models to
      examine the association of blood markers of vitamin B(12) status to change in
      cognitive scores over 6 years. Cognitive function was assessed every 3 years and
      measured as the sum of standardized scores on four tests. RESULTS: Probable
      vitamin B(12) deficiency was observed in 14.2% of the sample. Elevated serum
      concentrations of homocysteine were present in 19.2% of subjects, and of
      methylmalonic acid, in 36.4%. Higher serum methylmalonic acid concentrations were
      predictive of faster rates of cognitive decline (beta = -0.00016, SE = 0.0001, p
      = 0.004) and higher serum vitamin B(12) concentrations were associated with
      slower rates of cognitive decline (beta = +0.00013, SE < 0.0001, p = 0.005) in
      multivariable adjusted mixed models. Serum concentrations of homocysteine had no
      relationship to cognitive decline. CONCLUSIONS: Serum methylmalonic acid and
      vitamin B(12) concentrations may be the more important risk factors for cognitive
      decline when compared to serum homocysteine concentrations, particularly in older
      populations exposed to food fortification and possible supplements containing
      folic acid.

PMID- 19171836
TI  - Novel FHL1 mutations in fatal and benign reducing body myopathy.

PMID- 19171835
TI  - Vascular risk factors and dementia: how to move forward?
AB  - In recent years, accumulating evidence has suggested that vascular risk factors
      contribute to Alzheimer disease (AD). Vascular dementia had been traditionally
      considered secondary to stroke and vascular disease. It has been traditionally
      distinguished from AD, considered to be a purely neurodegenerative form of
      dementia. However, in light of this more recent literature, it appears that there
      is a spectrum: ranging from patients with pure vascular dementia to patients with
      pure AD and including a large majority of patients with contributions from both
      Alzheimer and vascular pathologies. In this article, we discuss the impact of
      vascular risk factors on AD and its consequences at the individual level and at
      the population level by highlighting the concept of attributable risk. We then
      discuss the key questions and next steps involved in designing a therapeutic
      trial to control vascular risk factors for the prevention of dementia.

PMID- 19171837
TI  - Elemental mercury neurotoxicity from self-injection.

PMID- 19171838
TI  - Linezolid inducing complex partial status epilepticus in a patient with epilepsy.

PMID- 19171839
TI  - Reflections: neurology and the humanities. Poems.

PMID- 19171840
TI  - Open-ring peripherally enhancing lesion of the cervical spine.

PMID- 19171841
TI  - Re: Practice parameter: assessing patients in a neurology practice for risk of
      falls (an evidence-based review): report of the Quality Standards Subcommittee of
      the American Academy of Neurology.

PMID- 19171842
TI  - Re: A randomized, placebo-controlled trial of repeated IV antibiotic therapy for
      Lyme encephalopathy. Prolonged Lyme disease treatment: enough is enough.

PMID- 19171843
TI  - Leptin and insulin resistance: good, bad, or still unclear?

PMID- 19171845
TI  - Adiponectin and inflammation.

PMID- 19171846
TI  - Surrogate measures of insulin resistance: of rats, mice, and men.

PMID- 19171848
TI  - Letter to the editor: "does baroreflex unloading decrease limb venous compliance
      in women?".

PMID- 19171847
TI  - Matrix metalloproteinase-9-mediated tissue injury overrides the protective effect
      of matrix metalloproteinase-2 during colitis.
AB  - Matrix metalloproteinases (MMP) play an important role in pathogenesis of
      inflammatory bowel disease (IBD). Two known gelatinases, MMP-2 and MMP-9, are
      upregulated during IBD. Epithelial-derived MMP-9 is an important mediator of
      tissue injury in colitis, whereas MMP-2 protects against tissue damage and
      maintains gut barrier function. It has been suggested that developing strategies
      to block MMP-9 activity in the gut might be of benefit to IBD. However, given
      that MMP-2 and MMP-9 are structurally similar, such approaches would also likely
      inhibit MMP-2. Thus, to gain insight into outcome of inhibiting both MMP-2 and
      MMP-9, MMP-2(-/-)/MMP-9(-/-) double knockout mice (dKO) lacking both MMP-2 and
      MMP-9 were used in this study. Three models of murine colitis were used: dextran
      sodium sulfate (DSS), Salmonella typhimurium (S.T.), and trinitrobenzene sulfonic
      acid (TNBS). Our data demonstrate that MMP-2 and MMP-9 activities were highly
      upregulated in wild-type (WT) mice treated with DSS, S.T., or TNBS whereas dKO
      mice were resistant to the development of colitis. WT mice had extensive
      inflammation and tissue damage compared with dKO mice as suggested by
      histological assessment and myeloperoxidase activity. In conclusion, these
      results suggest an overriding role of MMP-9 in mediating tissue injury compared
      with the protective role of MMP-2 in development of colitis. Thus inhibition of
      MMP-9 may be beneficial in treatment of colitis even if resulting in inhibition
      of MMP-2.

PMID- 19171850
TI  - Waiting list mortality among children listed for heart transplantation in the
      United States.
AB  - BACKGROUND: Children listed for heart transplantation face the highest waiting
      list mortality in solid-organ transplantation medicine. We examined waiting list
      mortality since the pediatric heart allocation system was revised in 1999 to
      determine whether the revised allocation system is prioritizing patients
      optimally and to identify specific high-risk populations that may benefit from
      emerging pediatric cardiac assist devices. METHODS AND RESULTS: We conducted a
      multicenter cohort study using the US Scientific Registry of Transplant
      Recipients. All children <18 years of age who were listed for a heart transplant
      between 1999 and 2006 were included. Among 3098 children, the median age was 2
      years (interquartile range 0.3 to 12 years), and median weight was 12.3 kg
      (interquartile range 5 to 38 kg); 1294 (42%) were nonwhite; and 1874 (60%) were
      listed as status 1A (of whom 30% were ventilated and 18% were on extracorporeal
      membrane oxygenation). Overall, 533 (17%) died, 1943 (63%) received transplants,
      and 252 (8%) recovered; 370 (12%) remained listed. Multivariate predictors of
      waiting list mortality include extracorporeal membrane oxygenation support
      (hazard ratio [HR] 3.1, 95% confidence interval [CI] 2.4 to 3.9), ventilator
      support (HR 1.9, 95% CI 1.6 to 2.4), listing status 1A (HR 2.2, 95% CI 1.7 to
      2.7), congenital heart disease (HR 2.2, 95% CI 1.8 to 2.6), dialysis support (HR
      1.9, 95% CI 1.2 to 3.0), and nonwhite race/ethnicity (HR 1.7, 95% CI 1.4 to 2.0).
      CONCLUSIONS: US waiting list mortality for pediatric heart transplantation
      remains unacceptably high in the current era. Specific high-risk subgroups can be
      identified that may benefit from emerging pediatric cardiac assist technologies.
      The current pediatric heart-allocation system captures medical urgency poorly.
      Further research is needed to define the optimal organ-allocation system for
      pediatric heart transplantation.

PMID- 19171851
TI  - Fluid retention is associated with cardiovascular mortality in patients
      undergoing long-term hemodialysis.
AB  - BACKGROUND: Patients with chronic kidney disease (stage 5) who undergo
      hemodialysis treatment have similarities to heart failure patients in that both
      populations retain fluid frequently and have excessively high mortality. Volume
      overload in heart failure is associated with worse outcomes. We hypothesized that
      in hemodialysis patients, greater interdialytic fluid gain is associated with
      poor all-cause and cardiovascular survival. METHODS AND RESULTS: We examined 2
      year (July 2001 to June 2003) mortality in 34,107 hemodialysis patients across
      the United States who had an average weight gain of at least 0.5 kg above their
      end-dialysis dry weight by the time the subsequent hemodialysis treatment
      started. The 3-month averaged interdialytic weight gain was divided into 8
      categories of 0.5-kg increments (up to > or =4.0 kg). Eighty-six percent of
      patients gained >1.5 kg between 2 dialysis sessions. In unadjusted analyses,
      higher weight gain was associated with better nutritional status (higher protein
      intake, serum albumin, and body mass index) and tended to be linked to greater
      survival. However, after multivariate adjustment for demographics (case mix) and
      surrogates of malnutrition-inflammation complex, higher weight-gain increments
      were associated with increased risk of all-cause and cardiovascular death. The
      hazard ratios (95% confidence intervals) of cardiovascular death for weight gain
      <1.0 kg and > or =4.0 kg (compared with 1.5 to 2.0 kg as the reference) were 0.67
      (0.58 to 0.76) and 1.25 (1.12 to 1.39), respectively. CONCLUSIONS: In
      hemodialysis patients, greater fluid retention between 2 subsequent hemodialysis
      treatment sessions is associated with higher risk of all-cause and cardiovascular
      death. The mechanisms by which fluid retention influences cardiovascular survival
      in hemodialysis may be similar to those in patients with heart failure and
      warrant further research.

PMID- 19171852
TI  - Early stent thrombosis in patients with acute coronary syndromes treated with
      drug-eluting and bare metal stents: the Acute Catheterization and Urgent
      Intervention Triage Strategy trial.
AB  - BACKGROUND: The clinical and angiographic predictors of early (<30 days) stent
      thrombosis (ST) have not been reported in high-risk patients with acute coronary
      syndromes. METHODS AND RESULTS: Qualitative and quantitative coronary
      angiographic analyses were performed in 3405 patients with moderate- and high
      risk acute coronary syndromes in whom stents were implanted in the prospective
      randomized Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY)
      trial, including 3043 patients (89.4%) in whom drug-eluting stents were
      implanted. Within 30 days, definite or probable ST occurred in 48 patients
      (1.4%). ST rates were not significantly different in patients treated with bare
      metal stents compared with drug-eluting stents (1.4% versus 1.4%; P=1.00) or with
      heparin plus glycoprotein IIb/IIIa inhibitors (1.1%) compared with bivalirudin
      with or without IIb/IIIa inhibitors (1.6% and 1.5%, respectively; P=0.26 and
      P=0.37, respectively). Compared with patients without ST, patients with ST more
      frequently had insulin-requiring diabetes mellitus and baseline renal
      insufficiency, a greater overall burden of coronary atherosclerosis, and
      suboptimal final angiographic results. ST also was more common in patients
      without preprocedural thienopyridine administration and with inconsistent
      antiplatelet drug use within 30 days. By multivariable analysis, the strongest
      independent predictors of definite ST were a smaller final stent minimal lumen
      diameter, a lack of preprocedural thienopyridine administration, the extent of
      coronary artery disease, and higher baseline hemoglobin level. CONCLUSIONS:
      Occurring in nearly 1 in 70 patients, early ST is relatively common in acute
      coronary syndromes, occurs with similar frequency after anticoagulation with
      either heparin plus glycoprotein IIb/IIIa inhibitors or bivalirudin with or
      without IIb/IIIa inhibitors, and is predicted by diffuse atherosclerosis,
      suboptimal angiographic results, and inadequate pharmacotherapy.

PMID- 19171853
TI  - Randomized comparison of everolimus-eluting and paclitaxel-eluting stents: two
      year clinical follow-up from the Clinical Evaluation of the Xience V Everolimus
      Eluting Coronary Stent System in the Treatment of Patients with de novo Native
      Coronary Artery Lesions (SPIRIT) III trial.
AB  - BACKGROUND: In the prospective randomized Clinical Evaluation of the Xience V
      Everolimus Eluting Coronary Stent System in the Treatment of Patients with de
      novo Native Coronary Artery Lesions (SPIRIT) III trial, an everolimus-eluting
      stent (EES) compared with a widely used paclitaxel-eluting stent (PES) resulted
      in a statistically significant reduction in angiographic in-segment late loss at
      8 months and noninferior rates of target vessel failure (cardiac death,
      myocardial infarction, or target vessel revascularization) at 1 year. The safety
      and efficacy of EES after 1 year have not been reported. METHODS AND RESULTS: A
      total of 1002 patients with up to 2 de novo native coronary artery lesions
      (reference vessel diameter, 2.5 to 3.75 mm; lesion length < or =28 mm) were
      randomized 2:1 to EES versus PES. Antiplatelet therapy consisted of aspirin
      indefinitely and a thienopyridine for > or =6 months. Between 1 and 2 years,
      patients treated with EES compared with PES tended to have fewer episodes of
      protocol-defined stent thrombosis (0.2% versus 1.0%; P=0.10) and myocardial
      infarctions (0.5% versus 1.7%; P=0.12), with similar rates of cardiac death (0.3%
      versus 0.3%; P=1.0) and target vessel revascularization (2.9% versus 3.0%;
      P=1.0). As a result, at the completion of the 2-year follow-up, treatment with
      EES compared with PES resulted in a significant 32% reduction in target vessel
      failure (10.7% versus 15.4%; hazard ratio, 0.68; 95% confidence interval, 0.48 to
      0.98; P=0.04) and a 45% reduction in major adverse cardiac events (cardiac death,
      myocardial infarction, or target lesion revascularization; 7.3% versus 12.8%;
      hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.83; P=0.004). Among the
      360 patients who discontinued clopidogrel or ticlopidine after 6 months, stent
      thrombosis subsequently developed in 0.4% of EES patients versus 2.6% of PES
      patients (P=0.10). CONCLUSIONS: Patients treated with EES rather than PES
      experienced significantly improved event-free survival at a 2-year follow-up in
      the SPIRIT III trial, with continued divergence of the hazard curves for target
      vessel failure and major adverse cardiac events between 1 and 2 years evident.
      The encouraging trends toward fewer stent thrombosis episodes after 6 months in
      EES-treated patients who discontinued a thienopyridine and after 1 year in all
      patients treated with EES rather than PES deserve further study.

PMID- 19171854
TI  - Continuous improvements in "chain of survival" increased survival after out-of
      hospital cardiac arrests: a large-scale population-based study.
AB  - BACKGROUND: The impact of ongoing efforts to improve the "chain of survival" for
      out-of-hospital cardiac arrest (OHCA) is unclear. The objective of this study was
      to evaluate the incremental effect of changes in prehospital emergency care on
      survival after OHCA. METHODS AND RESULTS: This prospective, population-based
      observational study involved consecutive patients with OHCA from May 1998 through
      December 2006. The primary outcome measure was 1-month survival with favorable
      neurological outcome. Multiple logistic regression analysis was used to assess
      factors that were potentially associated with better neurological outcome. Among
      42,873 resuscitation-attempted adult OHCAs, 8782 bystander-witnessed arrests of
      presumed cardiac origin were analyzed. The median time interval from collapse to
      call for medical help, first cardiopulmonary resuscitation, and first shock
      shortened from 4 (interquartile range [IQR] 2 to 11) to 2 (IQR 1 to 5) minutes,
      from 9 (IQR 5 to 13) to 7 (IQR 3 to 11) minutes, and from 19 (IQR 13 to 22) to 9
      (IQR 7 to 12) minutes, respectively. Neurologically intact 1-month survival after
      witnessed ventricular fibrillation increased from 6% (6/96) to 16% (49/297;
      P<0.001). Among all witnessed OHCAs, earlier cardiopulmonary resuscitation (odds
      ratio per minute 0.89, 95% confidence interval 0.85 to 0.93) and earlier
      intubation (odds ratio per minute 0.96, 95% confidence interval 0.94 to 0.99)
      were associated with better neurological outcome. For ventricular fibrillation,
      only earlier shock was associated with better outcome (odds ratio 0.84, 95%
      confidence interval 0.80 to 0.88). CONCLUSIONS: Data from a large, population
      based cohort demonstrate a continuous increase in OHCA survival with improvement
      in the chain of survival. The incremental benefit of early advanced care on OHCA
      survival is also suggested.

PMID- 19171855
TI  - Determinants of prolonged QT interval and their contribution to sudden death risk
      in coronary artery disease: the Oregon Sudden Unexpected Death Study.
AB  - BACKGROUND: In a recent cohort study, prolongation of the corrected QT interval
      (QTc) was associated with an independent increased risk of sudden cardiac death
      (SCD). We evaluated determinants of prolonged QTc and the relationship of
      prolonged QTc to SCD risk among patients with coronary artery disease in the
      general population. METHODS AND RESULTS: A case-control design was used. Cases
      were SCD patients with coronary artery disease among a metropolitan area of 1 000
      000 residents (2002 to 2006); controls were area residents with coronary artery
      disease but no history of SCD. All cases were required to have an ECG suitable
      for QTc analysis before and unrelated to the occurrence of SCD. A total of 373
      cases and 309 controls met criteria for analysis. Mean QTc was significantly
      longer in cases than in controls (450+/-45 versus 433+/-37 ms; P<0.0001). In a
      multivariate model, gender, diabetes mellitus, and QTc-prolonging drugs were
      significant determinants of QTc prolongation in controls. In a logistic
      regression model predicting SCD, diabetes mellitus (odds ratio, 1.97; 95%
      confidence interval, 1.32 to 2.96) and use of QTc-prolonging drugs (odds ratio,
      2.90; 95% confidence interval, 1.92 to 4.37) were significant predictors of SCD
      among subjects with normal or borderline QTc. However, abnormally prolonged QTc
      in the absence of diabetes and QT-prolonging medications was the strongest
      predictor of SCD (odds ratio, 5.53; 95% confidence interval, 3.20 to 9.57).
      CONCLUSIONS: Diabetes mellitus and QTc-affecting drugs determined QTc
      prolongation and were predictors of SCD in coronary artery disease. However,
      idiopathic abnormal QTc prolongation was associated with 5-fold increased odds of
      SCD. A continued search for novel determinants of QTc prolongation such as
      genomic factors is likely to enhance risk stratification for SCD in coronary
      artery disease.

PMID- 19171856
TI  - Dual angiogenic and neurotrophic effects of bone marrow-derived endothelial
      progenitor cells on diabetic neuropathy.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) are known to promote
      neovascularization in ischemic diseases. Recent evidence suggested that diabetic
      neuropathy is causally related to impaired angiogenesis and deficient growth
      factors. Accordingly, we investigated whether diabetic neuropathy could be
      reversed by local transplantation of EPCs. METHODS AND RESULTS: We found that
      motor and sensory nerve conduction velocities, blood flow, and capillary density
      were reduced in sciatic nerves of streptozotocin-induced diabetic mice but
      recovered to normal levels after hind-limb injection of bone marrow-derived EPCs.
      Injected EPCs were preferentially and durably engrafted in the sciatic nerves. A
      portion of engrafted EPCs were uniquely localized in close proximity to vasa
      nervorum, and a smaller portion of these EPCs were colocalized with endothelial
      cells. Multiple angiogenic and neurotrophic factors were significantly increased
      in the EPC-injected nerves. These dual angiogenic and neurotrophic effects of
      EPCs were confirmed by higher proliferation of Schwann cells and endothelial
      cells cultured in EPC-conditioned media. CONCLUSIONS: We demonstrate for the
      first time that bone marrow-derived EPCs could reverse various manifestations of
      diabetic neuropathy. These therapeutic effects were mediated by direct
      augmentation of neovascularization in peripheral nerves through long-term and
      preferential engraftment of EPCs in nerves and particularly vasa nervorum and
      their paracrine effects. These findings suggest that EPC transplantation could
      represent an innovative therapeutic option for treating diabetic neuropathy.

PMID- 19171857
TI  - Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from
      the American Heart Association Nutrition Subcommittee of the Council on
      Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing;
      and Council on Epidemiology and Prevention.

PMID- 19171858
TI  - Preoperative brain injury in transposition of the great arteries is associated
      with oxygenation and time to surgery, not balloon atrial septostomy.
AB  - BACKGROUND: Preoperative brain injury is an increasingly recognized phenomenon in
      neonates with complex congenital heart disease. Recently, reports have been
      published that associate preoperative brain injury in neonates with transposition
      of the great arteries with the performance of balloon atrial septostomy (BAS), a
      procedure that improves systemic oxygenation preoperatively. It is unclear
      whether BAS is the cause of brain injury or is a confounder, because neonates who
      require BAS are typically more hypoxemic. We sought to determine the relationship
      between preoperative brain injury in neonates with transposition of the great
      arteries and the performance of BAS. We hypothesized that brain injury results
      from hypoxic injury, not from the BAS itself. METHODS AND RESULTS: Infants with
      transposition of the great arteries (n=26) were retrospectively included from a
      larger cohort of infants with congenital heart disease who underwent preoperative
      brain MRI as part of 2 separate prospective studies. Data collected included all
      preoperative pulse oximetry recordings, all values from preoperative arterial
      blood gas measurements, and BAS procedure data. MRI scans were performed on the
      day of surgery, before the surgical repair. Of the 26 neonates, 14 underwent BAS.
      No stroke was seen in the entire cohort, whereas 10 (38%) of 26 patients were
      found to have hypoxic brain injury in the form of periventricular leukomalacia.
      Periventricular leukomalacia was not associated with BAS; however, neonates with
      periventricular leukomalacia had lower preoperative oxygenation (P=0.026) and a
      longer time to surgery (P=0.028) than those without periventricular leukomalacia.
      CONCLUSIONS: Preoperative brain injury in neonates with transposition of the
      great arteries is associated with hypoxemia and longer time to surgery. We found
      no association between BAS and brain injury.

PMID- 19171859
TI  - Retrograde type A aortic dissection after endovascular stent graft placement for
      treatment of type B dissection.
AB  - BACKGROUND: Retrograde type A aortic dissection has been deemed a rare
      complication after endovascular stent graft placement for type B dissection.
      However, this life-threatening event appears to be underrecognized and is worth
      being investigated further. METHODS AND RESULTS: Eleven of 443 patients developed
      retrograde type A aortic dissection during or after stent grafting for type B
      dissection from August 2000 to June 2007. Of these 11 patients, 3 had Marfan
      syndrome. The Kaplan-Meier estimate of the rate of freedom from this event at 36
      months is 97.4% (95% confidence interval, 0.95 to 0.99). The new entry was
      located at the tip of the proximal bare spring of the stent graft in 9 patients,
      was within the anchoring area of the proximal bare spring in 1, and remained
      unknown in 1 patient. Eight patients were converted to open surgery, and 2
      received medical treatment. One patient suddenly died 2 hours after the primary
      stent grafting, and 2 died within 1 week after the surgical conversion, so
      mortality reached 27.3%. During the follow-up from 3 to 50 months, type I
      endoleak was identified in 1 patient 3 months after the surgical exploration and
      disappeared at 6 months. CONCLUSIONS: Retrograde type A aortic dissection after
      stent grafting for type B dissection appears not to be rare and results from
      mixed causes. Fragility of the aortic wall and disease progression may predispose
      to it, whereas stent grafting-related factors make important and provocative
      contributions. Avoiding aortic arch stent grafting in Marfan patients, preferably
      selecting the endograft without the proximal bare spring for patients with a
      kinked aortic arch or with Marfan syndrome (if endografting is used), improving
      the device design, and standardizing endovascular manipulation might lessen its
      occurrence.

PMID- 19171860
TI  - Images in cardiovascular medicine. Newly discovered heart murmur: noncoronary
      sinus of valsalva aneurysm with rupture into the right atrium and right
      ventricle.

PMID- 19171861
TI  - Letter by Reiffel regarding article, "Acute pharmacological conversion of atrial
      fibrillation to sinus rhythm".

PMID- 19171862
TI  - Letter by Abdellaoui et al regarding article, "Intracoronary compared with
      intravenous bolus abciximab application in patients with ST-elevation myocardial
      infarction undergoing primary percutaneous coronary intervention".

PMID- 19171864
TI  - "Risky business": ten years is not a lifetime.

PMID- 19171865
TI  - Copayment levels and medication adherence: less is more.

PMID- 19171866
TI  - What price to pay? The cost of everything and the value of nothing.

PMID- 19171867
TI  - Antihypertensive efficacy of aliskiren: is hydrochlorothiazide an appropriate
      benchmark?

PMID- 19171868
TI  - Evolutionary genetics of coronary heart disease.

PMID- 19171869
TI  - Cardiovascular magnetic resonance imaging for valvular heart disease: technique
      and validation.

PMID- 19171870
TI  - Images in cardiovascular medicine. Local erosions of a bioprosthetic aortic valve
      cusp caused by towering ring suture knots too close to the valve.

PMID- 19171871
TI  - Heart disease and stroke statistics--2009 update: a report from the American
      Heart Association Statistics Committee and Stroke Statistics Subcommittee.

PMID- 19171872
TI  - Inhibition of aurora kinases for tailored risk-adapted treatment of multiple
      myeloma.
AB  - Genetic instability and cellular proliferation have been associated with aurora
      kinase expression in several cancer entities, including multiple myeloma.
      Therefore, the expression of aurora-A, -B, and -C was determined by Affymetrix
      DNA microarrays in 784 samples including 2 independent sets of 233 and 345 CD138
      purified myeloma cells from previously untreated patients. Chromosomal
      aberrations were assessed by comprehensive interphase fluorescence in situ
      hybridization and proliferation of primary myeloma cells by propidium iodine
      staining. We found aurora-A and -B to be expressed at varying frequencies in
      primary myeloma cells of different patient cohorts, but aurora-C in testis cell
      samples only. Myeloma cell samples with detectable versus absent aurora-A
      expression show a significantly higher proliferation rate, but neither a higher
      absolute number of chromosomal aberrations (aneuploidy), nor of subclonal
      aberrations (chromosomal instability). The clinical aurora kinase inhibitor VX680
      induced apoptosis in 20 of 20 myeloma cell lines and 5 of 5 primary myeloma cell
      samples. Presence of aurora-A expression delineates significantly inferior event
      free and overall survival in 2 independent cohorts of patients undergoing high
      dose chemotherapy, independent from conventional prognostic factors. Using gene
      expression profiling, aurora kinase inhibitors as a promising therapeutic option
      in myeloma can be tailoredly given to patients expressing aurora-A, who in turn
      have an adverse prognosis.

PMID- 19171873
TI  - ICSBP-mediated immune protection against BCR-ABL-induced leukemia requires the
      CCL6 and CCL9 chemokines.
AB  - Interferon (IFN) is effective at inducing complete remissions in patients with
      chronic myelogenous leukemia (CML), and evidence supports an immune mechanism.
      Here we show that the type I IFNs (alpha and beta) regulate expression of the IFN
      consensus sequence-binding protein (ICSBP) in BCR-ABL-transformed cells and as
      shown previously for ICSBP, induce a vaccine-like immunoprotective effect in a
      murine model of BCR-ABL-induced leukemia. We identify the chemokines CCL6 and
      CCL9 as genes prominently induced by the type I IFNs and ICSBP, and demonstrate
      that these immunomodulators are required for the immunoprotective effect of ICSBP
      expression. Insights into the role of these chemokines in the antileukemic
      response of IFNs suggest new strategies for immunotherapy of CML.

PMID- 19171874
TI  - C1q enhances IFN-gamma production by antigen-specific T cells via the CD40
      costimulatory pathway on dendritic cells.
AB  - Dendritic cells (DCs) are known to produce C1q, the initiator of the classical
      complement pathway. We demonstrate that murine DCs deficient in C1q (C1qa(-/-))
      are poorer than wild-type (WT) DCs at eliciting the proliferation and Th1
      differentiation of antigen-specific T cells. These defects result from decreased
      production of IL-12p70 by C1qa(-/-) DCs and impaired expression of costimulatory
      molecules CD80 and CD86 in response to CD40 ligation. The defective production of
      IL-12p70 and the reduced expression of CD80 and CD86 by C1qa(-/-) DCs were
      specifically mediated via CD40 ligation, as normal levels of IL-12p70 and CD80/86
      were observed after ligation of Toll-like receptors (TLRs) on C1qa(-/-) DCs. CD40
      ligation on C1qa(-/-) DCs, but not TLR ligation, results in decreased
      phosphorylation of p38 and ERK1/2 kinases. A strong colocalization of CD40 and
      C1q was observed by confocal microscopy upon CD40 ligation (but not TLR ligation)
      on DCs. Furthermore, human DCs from 2 C1q-deficient patients were found to have
      impaired IL-12p70 production in response to CD40L stimulation. Our novel data
      suggest that C1q augments the production of IL-12p70 by mouse and human DCs after
      CD40 triggering and plays important roles in sustaining the maturation of DCs and
      guiding the activation of T cells.

PMID- 19171875
TI  - Mature human eosinophils express functional Notch ligands mediating eosinophil
      autocrine regulation.
AB  - Eosinophil chemotaxis and survival within tissues are key components in the
      development of tissue eosinophilia and subsequent effector responses. In this
      study, we demonstrate a novel mechanism of eosinophil autoregulation affecting
      migration and survival mediated through Notch signaling. We show for the first
      time that human blood eosinophils express Notch receptors and Notch ligands,
      expressions of which are influenced by the presence of eosinophil-activating
      granulocyte-macrophage colony-stimulating factor (GM-CSF). Evidence of Notch
      receptor activation and subsequent transcription of the Notch-responsive gene
      HES1 were observed in GM-CSF-stimulated eosinophils, confirming functionality of
      eosinophil-expressed Notch-signaling components. Moreover, by inhibiting Notch
      signaling with gamma-secretase inhibitors or Notch receptor-specific neutralizing
      antibodies, we demonstrate that autocrine Notch signaling enhances stimulus
      mediated actin rearrangement and eosinophil chemokinesis, and impairs eosinophil
      viability. Taken together, these data suggest autocrine Notch signaling, enhanced
      in response to tissue- or inflammatory-derived signals, influences eosinophil
      activity and longevity, which may ultimately contribute to the development of
      tissue eosinophilia and exacerbation or remediation of eosinophil effector
      functions.

PMID- 19171877
TI  - Expression of the leukemia oncogene Lmo2 is controlled by an array of tissue
      specific elements dispersed over 100 kb and bound by Tal1/Lmo2, Ets, and Gata
      factors.
AB  - The Lmo2 gene encodes a transcriptional cofactor critical for the development of
      hematopoietic stem cells. Ectopic LMO2 expression causes leukemia in T-cell acute
      lymphoblastic leukemia (T-ALL) patients and severe combined immunodeficiency
      patients undergoing retroviral gene therapy. Tightly controlled Lmo2 expression
      is therefore essential, yet no comprehensive analysis of Lmo2 regulation has been
      published so far. By comparative genomics, we identified 17 highly conserved
      noncoding elements, 9 of which revealed specific acetylation marks in chromatin
      immunoprecipitation and microarray (ChIP-chip) assays performed across 250 kb of
      the Lmo2 locus in 11 cell types covering different stages of hematopoietic
      differentiation. All candidate regulatory regions were tested in transgenic mice.
      An extended LMO2 proximal promoter fragment displayed strong endothelial
      activity, while the distal promoter showed weak forebrain activity. Eight of the
      15 distal candidate elements functioned as enhancers, which together
      recapitulated the full expression pattern of Lmo2, directing expression to
      endothelium, hematopoietic cells, tail, and forebrain. Interestingly, distinct
      combinations of specific distal regulatory elements were required to extend
      endothelial activity of the LMO2 promoter to yolk sac or fetal liver
      hematopoietic cells. Finally, Sfpi1/Pu.1, Fli1, Gata2, Tal1/Scl, and Lmo2 were
      shown to bind to and transactivate Lmo2 hematopoietic enhancers, thus identifying
      key upstream regulators and positioning Lmo2 within hematopoietic regulatory
      networks.

PMID- 19171876
TI  - Regulation of macrophage function in tumors: the multifaceted role of NF-kappaB.
AB  - The pivotal role of tumor-associated macrophages (TAMs) in tumor progression is
      now well established. TAMs have been shown to influence multiple steps in tumor
      development including the growth, survival, invasion, and metastasis of tumor
      cells as well as angiogenesis and lymphangiogenesis in tumors. The molecular
      circuits that polarize TAMs toward such a protumoral phenotype are now the focus
      of intense investigation. The transcription factor, nuclear factor-kappaB (NF
      kappaB), is a master regulator of many cellular processes and been shown to
      regulate various pathways that impact on the function of TAMs. Much evidence for
      this has come from the use of elegant transgenic murine tumor models in which
      modification of single components of the NF-kappaB signaling pathway has been
      shown to regulate the pro-tumor repertoire of TAMs. Here, we outline this
      evidence and attempt to reconcile the various views that have emerged recently
      over the exact role of NF-kappaB in this phenomenon.

PMID- 19171878
TI  - Th-1 polarization is regulated by dendritic-cell comparison of MHC class I and
      class II antigens.
AB  - In the control of T-helper type I (Th-1) polarization, dendritic cells (DCs) must
      interpret a complex array of stimuli, many of which are poorly understood. Here
      we demonstrate that Th-1 polarization is heavily influenced by DC-autonomous
      phenomena triggered by the loading of DCs with antigenically matched major
      histocompatibility complex (MHC) class I and class II determinants, that is,
      class I and II peptide epitopes exhibiting significant amino acid sequence
      overlap (such as would be physiologically present during infectious processes
      requiring Th-1 immunity for clearance). Data were derived from 13 independent
      antigenic models including whole-cell systems, single-protein systems, and 3
      different pairs of overlapping class I and II binding epitopes. Once loaded with
      matched class I and II antigens, these "Th-1 DCs" exhibited differential cytokine
      secretion and surface marker expression, a distinct transcriptional signature,
      and acquired the ability to enhance generation of CD8(+) T lymphocytes.
      Mechanistically, tRNA-synthetases were implicated as components of a putative
      sensor complex involved in the comparison of class I and II epitopes. These data
      provide rigorous conceptual explanations for the process of Th-1 polarization and
      the antigenic specificity of cognate T-cell help, enhance the understanding of Th
      1 responses, and should contribute to the formulation of more effective
      vaccination strategies.

PMID- 19171880
TI  - Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of
      acute myeloid leukemia with a distinctive gene expression profile that is
      uniquely associated with a favorable outcome.
AB  - Mutations in CCAAT/enhancer binding protein alpha (CEBPA) are seen in 5% to 14%
      of acute myeloid leukemia (AML) and have been associated with a favorable
      clinical outcome. Most AMLs with CEBPA mutations simultaneously carry 2 mutations
      (CEBPA(double-mut)), usually biallelic, whereas single heterozygous mutations
      (CEBPA(single-mut)) are less frequently seen. Using denaturing high-performance
      liquid chromatography and nucleotide sequencing, we identified among a cohort of
      598 newly diagnosed AMLs a subset of 41 CEBPA mutant cases (28 CEBPA(double-mut)
      and 13 CEBPA(single-mut) cases). CEBPA(double-mut) associated with a unique gene
      expression profile as well as favorable overall and event-free survival, retained
      in multivariable analysis that included cytogenetic risk, FLT3-ITD and NPM1
      mutation, white blood cell count, and age. In contrast, CEBPA(single-mut) AMLs
      did not express a discriminating signature and could not be distinguished from
      wild-type cases as regards clinical outcome. These results demonstrate
      significant underlying heterogeneity within CEBPA mutation-positive AML with
      prognostic relevance.

PMID- 19171879
TI  - IL-17-producing human peripheral regulatory T cells retain suppressive function.
AB  - Although implicated in antagonistic functions, both regulatory T cells (Tregs)
      and Th17 effector cells play an important role in controlling autoimmune
      pathogenesis. Paradoxically, recent studies indicate that Tregs have the capacity
      to produce interleukin-17 (IL-17), although the ability of these cells to retain
      their suppressive function remains unknown. Here we report that human Tregs
      within the CD4(+)CD45RA(-)CD25(high)CCR6(+)HLA-DR(-)FoxP3(+) population produce
      IL-17 when activated in the presence of the proinflammatory cytokines IL-1beta
      and IL-6, whereas IL-17 secretion was inhibited by TGFbeta. To assess the ability
      of a single Treg to secrete IL-17 and to suppress in vitro immune function, we
      isolated clones from this population. We found that IL-17(+)/FoxP3(+) Treg clones
      retain suppressive function and exhibit the plasticity to secrete IL-17 or
      suppress depending on the nature of the stimulus provided. IL-17 production by
      these Treg clones was accompanied by sustained FoxP3 expression and concomitant,
      but reversible, loss of suppressive activity. Our data demonstrate that at the
      single cell level a subset of in vitro suppressive FoxP3(+) cells can be driven
      to secrete IL-17 under inflammatory conditions. These findings suggest a new
      mechanism by which inflammation can drive Tregs to secrete IL-17, thereby
      dampening suppression and promoting an inflammatory milieu.

PMID- 19171881
TI  - Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid
      leukemia.
AB  - Wilms tumor 1 (WT1) mutations have recently been identified in approximately 10%
      of adult acute myeloid leukemia (AML) with normal cytogenetics (CN-AML) and are
      associated with poor outcome. Using array-based comparative genome hybridization
      in pediatric CN-AML samples, we detected a WT1 deletion in one sample. The other
      WT1 allele was mutated. This prompted us to further investigate the role of WT1
      aberrations in childhood AML. Mutations were found in 35 of 298 (12%) diagnostic
      pediatric AML samples. In 19 of 35 (54%) samples, more than one WT1 aberration
      was found: 15 samples had 2 different mutations, 2 had a homozygous mutation, and
      2 had a mutation plus a WT1 deletion. WT1 mutations clustered significantly in
      the CN-AML subgroup (22%; P < .001) and were associated with FLT3/ITD (43 vs 17%;
      P < .001). WT1 mutations conferred an independent poor prognostic significance
      (WT1 mutated vs wild-type patients: 5-year probability of overall survival [pOS]
      35% vs 66%, P = .002; probability of event-free survival 22% vs 46%, P < .001;
      and cumulative incidence of relapse or regression 70% vs 44%, P < .001). Patients
      with both a WT1 mutation and a FLT3/ITD had a dismal prognosis (5-year pOS 21%).
      WT1 mutations occur at a significant rate in childhood AML and are a novel
      independent poor prognostic marker.

PMID- 19171882
TI  - Light-assisted deep-trapping of holes in conjugated polymers.
AB  - The injection of positive charge carriers (holes) into a single conjugated
      polymer chain was observed to be light-assisted. This effect may underlie
      critical, poorly understood organic electronic device phenomena such as the build
      up of functional deeply trapped charge layers in polymer light emitting diodes.
      The charging/discharging dynamics were investigated indirectly by a variety of
      single molecule electro-optical spectroscopic techniques, including an "image
      capture" approach.

PMID- 19171883
TI  - Beta2-adrenoceptor signaling is required for the development of an asthma
      phenotype in a murine model.
AB  - Chronic regular use of beta(2)-adrenoceptor (beta(2)-AR) agonists in asthma is
      associated with a loss of disease control and increased risk of death.
      Conversely, we have found that administration of beta(2)-AR inverse agonists
      results in attenuation of the asthma phenotype in an allergen-driven murine
      model. Besides antagonizing agonist-induced signaling and reducing signaling by
      empty receptors, beta-AR inverse agonists can also activate signaling by novel
      pathways. To determine the mechanism of the beta-AR inverse agonists, we compared
      the asthma phenotype in beta(2)-AR-null and wild-type mice. Antigen challenge of
      beta(2)-AR-null mice produced results similar to what was observed with chronic
      beta(2)-AR inverse agonist treatment, namely, reductions in mucous metaplasia,
      airway hyperresponsiveness (AHR), and inflammatory cells in the lungs. These
      results indicate that the effects of beta(2)-AR inverse agonists are caused by
      inhibition of beta(2)-AR signaling rather than by the induction of novel
      signaling pathways. Chronic administration of alprenolol, a beta-blocker without
      inverse agonist properties, did not attenuate the asthma phenotype, suggesting
      that it is signaling by empty receptors, rather than agonist-induced beta(2)-AR
      signaling, that supports the asthma phenotype. In conclusion, our results
      demonstrate that, in a murine model of asthma, beta(2)-AR signaling is required
      for the full development of three cardinal features of asthma: mucous metaplasia,
      AHR, and the presence of inflammatory cells in the lungs.

PMID- 19171884
TI  - Progressive aggregation despite chaperone associations of a mutant SOD1-YFP in
      transgenic mice that develop ALS.
AB  - Recent studies suggest that superoxide dismutase 1 (SOD1)-linked amyotrophic
      lateral sclerosis results from destabilization and misfolding of mutant forms of
      this abundant cytosolic enzyme. Here, we have tracked the expression and fate of
      a misfolding-prone human SOD1, G85R, fused to YFP, in a line of transgenic G85R
      SOD1-YFP mice. These mice, but not wild-type human SOD1-YFP transgenics,
      developed lethal paralyzing motor symptoms at 9 months. In situ RNA hybridization
      of spinal cords revealed predominant expression in motor neurons in spinal cord
      gray matter in all transgenic animals. Concordantly, G85R SOD-YFP was diffusely
      fluorescent in motor neurons of animals at 1 and 6 months of age, but at the time
      of symptoms, punctate aggregates were observed in cell bodies and processes.
      Biochemical analyses of spinal cord soluble extracts indicated that G85R SOD-YFP
      behaved as a misfolded monomer at all ages. It became progressively insoluble at
      6 and 9 months of age, associated with presence of soluble oligomers observable
      by gel filtration. Immunoaffinity capture and mass spectrometry revealed
      association of G85R SOD-YFP, but not WT SOD-YFP, with the cytosolic chaperone
      Hsc70 at all ages. In addition, 3 Hsp110's, nucleotide exchange factors for
      Hsp70s, were captured at 6 and 9 months. Despite such chaperone interactions,
      G85R SOD-YFP formed insoluble inclusions at late times, containing predominantly
      intermediate filament proteins. We conclude that motor neurons, initially
      "compensated" to maintain the misfolded protein in a soluble state, become
      progressively unable to do so.

PMID- 19171886
TI  - Design of 240,000 orthogonal 25mer DNA barcode probes.
AB  - DNA barcodes linked to genetic features greatly facilitate screening these
      features in pooled formats using microarray hybridization, and new tools are
      needed to design large sets of barcodes to allow construction of large barcoded
      mammalian libraries such as shRNA libraries. Here we report a framework for
      designing large sets of orthogonal barcode probes. We demonstrate the utility of
      this framework by designing 240,000 barcode probes and testing their performance
      by hybridization. From the test hybridizations, we also discovered new probe
      design rules that significantly reduce cross-hybridization after their
      introduction into the framework of the algorithm. These rules should improve the
      performance of DNA microarray probe designs for many applications.

PMID- 19171885
TI  - Morphological and functional reorganization of rat medial prefrontal cortex in
      neuropathic pain.
AB  - Neuropathic pain is a chronic pain that results from lesion or dysfunction of the
      nervous system. Depression and cognitive decline are often coupled to chronic
      pain, suggesting the involvement of cortical areas associated with higher
      cognitive functions. We investigated layer 2/3 pyramidal neurons in acute slices
      of the contralateral medial prefrontal cortex (mPFC) in the rat spared nerve
      injury (SNI) model of neuropathic pain and found morphological and functional
      differences between the mPFC of SNI and sham-operated animals. Basal, but not
      apical, dendrites of neurons from SNI rats are longer and have more branches than
      their counterparts in sham-operated animals; spine density is also selectively
      increased in basal dendrites of neurons from SNI rats; the morphological changes
      are accompanied by increased contribution to synaptic currents of the NMDA
      component. Interestingly, the NMDA/AMPA ratio of the synaptic current elicited in
      mPFC neurons by afferent fiber stimulation shows linear correlation with the
      rats' tactile threshold in the injured (but not in the contralateral) paw. Our
      results not only provide evidence that neuropathic pain leads to rearrangement of
      the mPFC, which may help defining the cellular basis for cognitive impairments
      associated with chronic pain, but also show pain-associated morphological changes
      in the cortex at single neuron level.

PMID- 19171887
TI  - C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia.
AB  - Mincle (also called as Clec4e and Clecsf9) is a C-type lectin receptor expressed
      in activated phagocytes. Recently, we have demonstrated that Mincle is an
      FcRgamma-associated activating receptor that senses damaged cells. To search an
      exogenous ligand(s), we screened pathogenic fungi using cell line expressing
      Mincle, FcRgamma, and NFAT-GFP reporter. We found that Mincle specifically
      recognizes the Malassezia species among 50 different fungal species tested.
      Malassezia is a pathogenic fungus that causes skin diseases, such as tinea
      versicolor and atopic dermatitis, and fatal sepsis. However, the specific
      receptor on host cells has not been identified. Mutation of the putative mannose
      binding motif within C-type lectin domain of Mincle abrogated Malassezia
      recognition. Analyses of glycoconjugate microarray revealed that Mincle
      selectively binds to alpha-mannose but not mannan. Thus, Mincle may recognize
      specific geometry of alpha-mannosyl residues on Malassezia species and use this
      to distinguish them from other fungi. Malassezia activated macrophages to produce
      inflammatory cytokines/chemokines. To elucidate the physiological function of
      Mincle, Mincle-deficient mice were established. Malassezia-induced
      cytokine/chemokine production by macrophages from Mincle(-/-) mice was
      significantly impaired. In vivo inflammatory responses against Malassezia was
      also impaired in Mincle(-/-) mice. These results indicate that Mincle is the
      first specific receptor for Malassezia species to be reported and plays a crucial
      role in immune responses to this fungus.

PMID- 19171888
TI  - Nodal points and complexity of Notch-Ras signal integration.
AB  - Metazoans use a handful of highly conserved signaling pathways to create a
      signaling backbone that governs development. How these few signals have such a
      versatile action likely depends upon the larger-scale network they form through
      integration, as exemplified by cross-talk between the Notch and receptor tyrosine
      kinase (RTK) pathways. We examined the transcriptional output of Notch-RTK cross
      talk during Drosophila development and present in vivo data supporting a role for
      selected mutually regulated genes in signal integration. Interestingly, Notch-RTK
      integration did not lead to general antagonism of either pathway, as is commonly
      believed. Instead, integration had a combinatorial effect on specific cross
      regulated targets, which unexpectedly included numerous core components of the
      RTK and other major signaling pathways (TGF-beta, Hh, Jak/Stat, nuclear receptor
      and Wnt). We find the majority of Ras-responsive genes are also Notch-responsive,
      suggesting Notch may function to specify the response to Ras activation.

PMID- 19171889
TI  - The default mode network and self-referential processes in depression.
AB  - The recently discovered default mode network (DMN) is a group of areas in the
      human brain characterized, collectively, by functions of a self-referential
      nature. In normal individuals, activity in the DMN is reduced during nonself
      referential goal-directed tasks, in keeping with the folk-psychological notion of
      losing one's self in one's work. Imaging and anatomical studies in major
      depression have found alterations in both the structure and function in some
      regions that belong to the DMN, thus, suggesting a basis for the disordered self
      referential thought of depression. Here, we sought to examine DMN functionality
      as a network in patients with major depression, asking whether the ability to
      regulate its activity and, hence, its role in self-referential processing, was
      impaired. To do so, we asked patients and controls to examine negative pictures
      passively and also to reappraise them actively. In widely distributed elements of
      the DMN [ventromedial prefrontal cortex prefrontal cortex (BA 10), anterior
      cingulate (BA 24/32), lateral parietal cortex (BA 39), and lateral temporal
      cortex (BA 21)], depressed, but not control subjects, exhibited a failure to
      reduce activity while both looking at negative pictures and reappraising them.
      Furthermore, looking at negative pictures elicited a significantly greater
      increase in activity in other DMN regions (amygdala, parahippocampus, and
      hippocampus) in depressed than in control subjects. These data suggest depression
      is characterized by both stimulus-induced heightened activity and a failure to
      normally down-regulate activity broadly within the DMN. These findings provide a
      brain network framework within which to consider the pathophysiology of
      depression.

PMID- 19171890
TI  - Expression profiling during ocular development identifies 2 Nlz genes with a
      critical role in optic fissure closure.
AB  - The gene networks underlying closure of the optic fissure during vertebrate eye
      development are poorly understood. Here, we profile global gene expression during
      optic fissure closure using laser capture microdissected (LCM) tissue from the
      margins of the fissure. From these data, we identify a unique role for the
      C(2)H(2) zinc finger proteins Nlz1 and Nlz2 in normal fissure closure. Gene
      knockdown of nlz1 and/or nlz2 in zebrafish leads to a failure of the optic
      fissure to close, a phenotype which closely resembles that seen in human uveal
      coloboma. We also identify misregulation of pax2 in the developing eye of
      morphant fish, suggesting that Nlz1 and Nlz2 act upstream of the Pax2 pathway in
      directing proper closure of the optic fissure.

PMID- 19171891
TI  - Generalized ensemble methods for de novo structure prediction.
AB  - Current methods for predicting protein structure depend on two interrelated
      components: (i) an energy function that should have a low value near the correct
      structure and (ii) a method for searching through different conformations of the
      polypeptide chain. Identification of the most efficient search methods is
      essential if we are to be able to apply such methods broadly and with confidence.
      In addition, efficient search methods provide a rigorous test of existing energy
      functions, which are generally knowledge-based and contain different terms added
      together with arbitrary weights. Here, we test different search methods with one
      of the most accurate and predictive energy functions, namely Rosetta the
      knowledge-based force-field from Baker's group [Simons K, Kooperberg C, Huang E,
      Baker D (1997) J Mol Biol 268:209-225]. We use an implementation of a generalized
      ensemble search method to scale relevant parts of the energy function. This
      method, known as Hamiltonian Replica Exchange Monte Carlo, outperforms the
      original Monte Carlo Simulated Annealing used in the Rosetta package in terms of
      sampling low-energy states. It also outperforms another widely used generalized
      ensemble search method known as Temperature Replica Exchange Monte Carlo. Our
      results reveal clear deficiencies in the low-resolution Rosetta energy function
      in that the lowest energy structures are not necessarily the most native-like. By
      using a set of nonnative low-energy structures found by our extensive sampling,
      we discovered that the long-range and short-range backbone hydrogen-bonding
      energy terms of the Rosetta energy discriminate between the nonnative and native
      like structures significantly better than the low-resolution score used in
      Rosetta.

PMID- 19171892
TI  - Molecular recognition and self-assembly special feature: Dynamic combinatorial
      synthesis of a catenane based on donor-acceptor interactions in water.
AB  - A new type of neutral donor-acceptor [2]-catenane, containing both complementary
      units in the same ring was synthesized from a dynamic combinatorial library in
      water. The yield of the water soluble [2]-catenane is enhanced by increasing
      either building-block concentrations or ionic strength, or by the addition of an
      electron-rich template. NMR spectroscopy demonstrates that the template is
      intercalated between the 2 electron-deficient naphthalenediimide units of the
      catenane.

PMID- 19171893
TI  - Arabidopsis ORC1 is a PHD-containing H3K4me3 effector that regulates
      transcription.
AB  - Control of gene expression depends on a complex and delicate balance of various
      posttranslational modifications of histones. However, the relevance of specific
      combinations of histone modifications is not fully defined. Downstream effector
      proteins recognize particular histone modifications and transduce this
      information into gene expression patterns. Methylation of histone H3 at lysine 4
      (H3K4me) is a landmark of gene expression control in eukaryotes. Its recognition
      depends on the presence in the effector protein of a motif termed plant
      homeodomain (PHD) that specifically binds to H3K4me3. Here, we establish that
      Arabidopsis ORC1, the large subunit of the origin recognition complex involved in
      defining origins of DNA replication, functions as a transcriptional activator of
      a subset of genes, the promoters of which are preferentially bound by ORC1.
      Arabidopsis ORC1 contains a PHD and binds to H3K4me3. In addition to H4
      acetylation, ORC1 binding correlates with increased H4K20me3 in the proximal
      promoter region of ORC1 targets. This suggests that H4K20me3, unlike in animal
      cells, is associated with transcriptional activation in Arabidopsis. Thus, our
      data provide a molecular basis for the opposite role of ORC1 in transcriptional
      activation in plants and repression in animals. Since only ORC1 proteins of plant
      species contain a PHD, we propose that plant ORC1 constitutes a novel class of
      H3K4me3 effector proteins characteristic of the plant kingdom.

PMID- 19171894
TI  - Newborn infants detect the beat in music.
AB  - To shed light on how humans can learn to understand music, we need to discover
      what the perceptual capabilities with which infants are born. Beat induction, the
      detection of a regular pulse in an auditory signal, is considered a fundamental
      human trait that, arguably, played a decisive role in the origin of music.
      Theorists are divided on the issue whether this ability is innate or learned. We
      show that newborn infants develop expectation for the onset of rhythmic cycles
      (the downbeat), even when it is not marked by stress or other distinguishing
      spectral features. Omitting the downbeat elicits brain activity associated with
      violating sensory expectations. Thus, our results strongly support the view that
      beat perception is innate.

PMID- 19171896
TI  - Phase separation in hydrogen-helium mixtures at Mbar pressures.
AB  - The properties of hydrogen-helium mixtures at Mbar pressures and intermediate
      temperatures (4000 to 10000 K) are calculated with first-principles molecular
      dynamics simulations. We determine the equation of state as a function of
      density, temperature, and composition and, using thermodynamic integration, we
      estimate the Gibbs free energy of mixing, thereby determining the temperature, at
      a given pressure, when helium becomes insoluble in dense metallic hydrogen. These
      results are directly relevant to models of the interior structure and evolution
      of Jovian planets. We find that the temperatures for the demixing of helium and
      hydrogen are sufficiently high to cross the planetary adiabat of Saturn at
      pressures approximately 5 Mbar; helium is partially miscible throughout a
      significant portion of the interior of Saturn, and to a lesser extent in Jupiter.

PMID- 19171895
TI  - Yeast telomere capping protein Stn1 overrides DNA replication control through the
      S phase checkpoint.
AB  - Telomere integrity is maintained through end-protection proteins that block
      nuclease degradation and prevent telomeres from being recognized as DNA breaks.
      Although less well understood, end protection proteins may also play a role in
      facilitating telomere replication. Here, we show that overproduction (OP) of the
      yeast telomere capping protein Stn1 makes cells highly sensitive to the
      replication inhibitors hydroxyurea (HU) and methyl-methane sulfonate (MMS).
      Unexpectedly, this sensitivity corresponds with Stn1 OP blocking most, if not
      all, aspects of the S phase checkpoint. The checkpoint kinase Rad53 is
      phosphorylated with normal timing in Stn1 OP cells, indicating Stn1 does not
      interfere with signaling steps involved in activating the checkpoint. Part of the
      role of Stn1 in telomere integrity is mediated through the Pol12 subunit of DNA
      polymerase alpha (Pol alpha). We show that overproduced Stn1 generally associates
      with chromosomes in HU treated and untreated cells, and, remarkably, Stn1
      chromosome binding and OP checkpoint defects are rescued in pol12 mutants. We
      propose Stn1 normally promotes Pol alpha activity at telomeres but can be
      recruited through Pol12 to nontelomeric sites when overproduced. During
      replication stress, the mislocalized Stn1 may inappropriately promote Pol alpha
      in a manner that interferes with Rad53 effector mechanisms controlling
      replication fork integrity.

PMID- 19171897
TI  - Cross-presenting human gammadelta T cells induce robust CD8+ alphabeta T cell
      responses.
AB  - Gammadelta T cells are implicated in host defense against microbes and tumors but
      their mode of function remains largely unresolved. Here, we have investigated the
      ability of activated human Vgamma9Vdelta2(+) T cells (termed gammadelta T-APCs)
      to cross-present microbial and tumor antigens to CD8(+) alphabeta T cells.
      Although this process is thought to be mediated best by DCs, adoptive transfer of
      ex vivo antigen-loaded, human DCs during immunotherapy of cancer patients has
      shown limited success. We report that gammadelta T-APCs take up and process
      soluble proteins and induce proliferation, target cell killing and cytokine
      production responses in antigen-experienced and naive CD8(+) alphabeta T cells.
      Induction of APC functions in Vgamma9Vdelta2(+) T cells was accompanied by the up
      regulation of costimulatory and MHC class I molecules. In contrast, the
      functional predominance of the immunoproteasome was a characteristic of
      gammadelta T cells irrespective of their state of activation. Gammadelta T-APCs
      were more efficient in antigen cross-presentation than monocyte-derived DCs,
      which is in contrast to the strong induction of CD4(+) alphabeta T cell responses
      by both types of APCs. Our study reveals unexpected properties of human
      gammadelta T-APCs in the induction of CD8(+) alphabeta T effector cells, and
      justifies their further exploration in immunotherapy research.

PMID- 19171898
TI  - Reversal of defective lysosomal transport in NPC disease ameliorates liver
      dysfunction and neurodegeneration in the npc1-/- mouse.
AB  - Niemann-Pick type C disease is largely attributable to an inactivating mutation
      of NPC1 protein, which normally aids movement of unesterified cholesterol (C)
      from the endosomal/lysosomal (E/L) compartment to the cytosolic compartment of
      cells throughout the body. This defect results in activation of macrophages in
      many tissues, progressive liver disease, and neurodegeneration. In the npc1(-/-)
      mouse, a model of this disease, the whole-animal C pool expands from 2,082 to
      4,925 mg/kg body weight (bw) and the hepatic C pool increases from 132 to 1,485
      mg/kg bw between birth and 49 days of age. A single dose of 2-hydroxypropyl-beta
      cyclodextrin (CYCLO) administered at 7 days of age immediately caused this
      sequestered C to flow from the lysosomes to the cytosolic pool in many organs,
      resulting in a marked increase in cholesteryl esters, suppression of C but not
      fatty acid synthesis, down-regulation of genes controlled by sterol regulatory
      element 2, and up-regulation of many liver X receptor target genes. There was
      also decreased expression of proinflammatory proteins in the liver and brain. In
      the liver, where the rate of C sequestration equaled 79 mg x d(-1) x kg(-1),
      treatment with CYCLO within 24 h increased C movement out of the E/L compartment
      from near 0 to 233 mg x d(-1) x kg(-1). By 49 days of age, this single injection
      of CYCLO resulted in a reduction in whole-body C burden of >900 mg/kg, marked
      improvement in liver function tests, much less neurodegeneration, and,
      ultimately, significant prolongation of life. These findings suggest that CYCLO
      acutely reverses the lysosomal transport defect seen in NPC disease.

PMID- 19171899
TI  - Knockdown of proteins involved in iron metabolism limits tick reproduction and
      development.
AB  - Ticks are among the most important vectors of a wide range of human and animal
      diseases. During blood feeding, ticks are exposed to an enormous amount of free
      iron that must be appropriately used and detoxified. However, the mechanism of
      iron metabolism in ticks is poorly understood. Here, we show that ticks possess a
      complex system that efficiently utilizes, stores and transports non-heme iron
      within the tick body. We have characterized a new secreted ferritin (FER2) and an
      iron regulatory protein (IRP1) from the sheep tick, Ixodes ricinus, and have
      demonstrated their relationship to a previously described tick intracellular
      ferritin (FER1). By using RNA interference-mediated gene silencing in the tick,
      we show that synthesis of FER1, but not of FER2, is subject to IRP1-mediated
      translational control. Further, we find that depletion of FER2 from the tick
      plasma leads to a loss of FER1 expression in the salivary glands and ovaries that
      normally follows blood ingestion. We therefore suggest that secreted FER2
      functions as the primary transporter of non-heme iron between the tick gut and
      the peripheral tissues. Silencing of the fer1, fer2, and irp1 genes by RNAi has
      an adverse impact on hatching rate and decreases postbloodmeal weight in tick
      females. Importantly, knockdown of fer2 dramatically impairs the ability of ticks
      to feed, thus making FER2 a promising candidate for development of an efficient
      anti-tick vaccine.

PMID- 19171900
TI  - Model of genetic variation in human social networks.
AB  - Social networks exhibit strikingly systematic patterns across a wide range of
      human contexts. Although genetic variation accounts for a significant portion of
      the variation in many complex social behaviors, the heritability of egocentric
      social network attributes is unknown. Here, we show that 3 of these attributes
      (in-degree, transitivity, and centrality) are heritable. We then develop a
      "mirror network" method to test extant network models and show that none account
      for observed genetic variation in human social networks. We propose an
      alternative "Attract and Introduce" model with two simple forms of heterogeneity
      that generates significant heritability and other important network features. We
      show that the model is well suited to real social networks in humans. These
      results suggest that natural selection may have played a role in the evolution of
      social networks. They also suggest that modeling intrinsic variation in network
      attributes may be important for understanding the way genes affect human
      behaviors and the way these behaviors spread from person to person.

PMID- 19171901
TI  - Caloric restriction improves memory in elderly humans.
AB  - Animal studies suggest that diets low in calories and rich in unsaturated fatty
      acids (UFA) are beneficial for cognitive function in age. Here, we tested in a
      prospective interventional design whether the same effects can be induced in
      humans. Fifty healthy, normal- to overweight elderly subjects (29 females, mean
      age 60.5 years, mean body mass index 28 kg/m(2)) were stratified into 3 groups:
      (i) caloric restriction (30% reduction), (ii) relative increased intake of UFAs
      (20% increase, unchanged total fat), and (iii) control. Before and after 3 months
      of intervention, memory performance was assessed under standardized conditions.
      We found a significant increase in verbal memory scores after caloric restriction
      (mean increase 20%; P < 0.001), which was correlated with decreases in fasting
      plasma levels of insulin and high sensitive C-reactive protein, most pronounced
      in subjects with best adherence to the diet (all r values < -0.8; all P values
      <0.05). Levels of brain-derived neurotrophic factor remained unchanged. No
      significant memory changes were observed in the other 2 groups. This
      interventional trial demonstrates beneficial effects of caloric restriction on
      memory performance in healthy elderly subjects. Mechanisms underlying this
      improvement might include higher synaptic plasticity and stimulation of
      neurofacilitatory pathways in the brain because of improved insulin sensitivity
      and reduced inflammatory activity. Our study may help to generate novel
      prevention strategies to maintain cognitive functions into old age.

PMID- 19171903
TI  - A hybrid nanomemristor/transistor logic circuit capable of self-programming.
AB  - Memristor crossbars were fabricated at 40 nm half-pitch, using nanoimprint
      lithography on the same substrate with Si metal-oxide-semiconductor field effect
      transistor (MOS FET) arrays to form fully integrated hybrid memory resistor
      (memristor)/transistor circuits. The digitally configured memristor crossbars
      were used to perform logic functions, to serve as a routing fabric for
      interconnecting the FETs and as the target for storing information. As an
      illustrative demonstration, the compound Boolean logic operation (A AND B) OR (C
      AND D) was performed with kilohertz frequency inputs, using resistor-based logic
      in a memristor crossbar with FET inverter/amplifier outputs. By routing the
      output signal of a logic operation back onto a target memristor inside the array,
      the crossbar was conditionally configured by setting the state of a nonvolatile
      switch. Such conditional programming illuminates the way for a variety of self
      programmed logic arrays, and for electronic synaptic computing.

PMID- 19171902
TI  - Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic
      oncogenesis involving stem cell marker Nanog.
AB  - Alcohol synergistically enhances the progression of liver disease and the risk
      for liver cancer caused by hepatitis C virus (HCV). However, the molecular
      mechanism of this synergy remains unclear. Here, we provide the first evidence
      that Toll-like receptor 4 (TLR4) is induced by hepatocyte-specific transgenic
      (Tg) expression of the HCV nonstructural protein NS5A, and this induction
      mediates synergistic liver damage and tumor formation by alcohol-induced
      endotoxemia. We also identify Nanog, the stem/progenitor cell marker, as a novel
      downstream gene up-regulated by TLR4 activation and the presence of CD133/Nanog
      positive cells in liver tumors of alcohol-fed NS5A Tg mice. Transplantation of
      p53-deficient hepatic progenitor cells transduced with TLR4 results in liver
      tumor development in mice following repetitive LPS injection, but concomitant
      transduction of Nanog short-hairpin RNA abrogates this outcome. Taken together,
      our study demonstrates a TLR4-dependent mechanism of synergistic liver disease by
      HCV and alcohol and an obligatory role for Nanog, a TLR4 downstream gene, in HCV
      induced liver oncogenesis enhanced by alcohol.

PMID- 19171904
TI  - Apoplastic effectors secreted by two unrelated eukaryotic plant pathogens target
      the tomato defense protease Rcr3.
AB  - Current models of plant-pathogen interactions stipulate that pathogens secrete
      effector proteins that disable plant defense components known as virulence
      targets. Occasionally, the perturbations caused by these effectors trigger innate
      immunity via plant disease resistance proteins as described by the "guard
      hypothesis." This model is nicely illustrated by the interaction between the
      fungal plant pathogen Cladosporium fulvum and tomato. C. fulvum secretes a
      protease inhibitor Avr2 that targets the tomato cysteine protease Rcr3(pim). In
      plants that carry the resistance protein Cf2, Rcr3(pim) is required for
      resistance to C. fulvum strains expressing Avr2, thus fulfilling one of the
      predictions of the guard hypothesis. Another prediction of the guard hypothesis
      has not yet been tested. Considering that virulence targets are important
      components of defense, different effectors from unrelated pathogens are expected
      to evolve to disable the same host target. In this study we confirm this
      prediction using a different pathogen of tomato, the oomycete Phytophthora
      infestans that is distantly related to fungi such as C. fulvum. This pathogen
      secretes an array of protease inhibitors including EPIC1 and EPIC2B that inhibit
      tomato cysteine proteases. Here we show that, similar to Avr2, EPIC1 and EPIC2B
      bind and inhibit Rcr3(pim). However, unlike Avr2, EPIC1 and EPIC2B do not trigger
      hypersensitive cell death or defenses on Cf-2/Rcr3(pim) tomato. We also found
      that the rcr3-3 mutant of tomato that carries a premature stop codon in the Rcr3
      gene exhibits enhanced susceptibility to P. infestans, suggesting a role for
      Rcr3(pim) in defense. In conclusion, our findings fulfill a key prediction of the
      guard hypothesis and suggest that the effectors Avr2, EPIC1, and EPIC2B secreted
      by two unrelated pathogens of tomato target the same defense protease Rcr3(pim).
      In contrast to C. fulvum, P. infestans appears to have evolved stealthy effectors
      that carry inhibitory activity without triggering plant innate immunity.

PMID- 19171905
TI  - BRG1 requirement for long-range interaction of a locus control region with a
      downstream promoter.
AB  - The dynamic packaging of DNA into chromatin is a fundamental step in the control
      of diverse nuclear processes. Whereas certain transcription factors and
      chromosomal components promote the formation of higher-order chromatin loops, the
      co-regulator machinery mediating loop assembly and disassembly is unknown. Using
      mice bearing a hypomorphic allele of the BRG1 chromatin remodeler, we demonstrate
      that the Brg1 mutation abrogated a cell type-specific loop between the beta
      globin locus control region and the downstream beta major promoter, despite trans
      acting factor occupancy at both sites. By contrast, distinct loops were
      insensitive to the Brg1 mutation. Molecular analysis with a conditional allele of
      GATA-1, a key regulator of hematopoiesis, in a novel cell-based system provided
      additional evidence that BRG1 functions early in chromatin domain activation to
      mediate looping. Although the paradigm in which chromatin remodelers induce
      nucleosome structural transitions is well established, our results demonstrating
      an essential role of BRG1 in the genesis of specific chromatin loops expands the
      repertoire of their functions.

PMID- 19171906
TI  - Dysregulation of CalDAG-GEFI and CalDAG-GEFII predicts the severity of motor side
      effects induced by anti-parkinsonian therapy.
AB  - Voluntary movement difficulties in Parkinson's disease are initially relieved by
      l-DOPA therapy, but with disease progression, the repeated l-DOPA treatments can
      produce debilitating motor abnormalities known as l-DOPA-induced dyskinesias. We
      show here that 2 striatum-enriched regulators of the Ras/Rap/ERK MAP kinase
      signal transduction cascade, matrix-enriched CalDAG-GEFI and striosome-enriched
      CalDAG-GEFII (also known as RasGRP), are strongly and inversely dysregulated in
      proportion to the severity of abnormal movements induced by l-DOPA in a rat model
      of parkinsonism. In the dopamine-depleted striatum, the l-DOPA treatments produce
      down-regulation of CalDAG-GEFI and up-regulation of CalDAG-GEFII mRNAs and
      proteins, and quantification of the mRNA levels shows that these changes are
      closely correlated with the severity of the dyskinesias. As these CalDAG-GEFs
      control ERK cascades, which are implicated in l-DOPA-induced dyskinesias, and
      have differential compartmental expression patterns in the striatum, we suggest
      that they may be key molecules involved in the expression of the dyskinesias.
      They thus represent promising new therapeutic targets for limiting the motor
      complications induced by l-DOPA therapy.

PMID- 19171907
TI  - The Src family kinase, Lyn, suppresses osteoclastogenesis in vitro and in vivo.
AB  - c-Src kinase is a rate-limiting activator of osteoclast (OC) function and Src
      inhibitors are therefore candidate antiosteoporosis drugs. By affecting
      alphavbeta3 and macrophage-colony stimulating factor (M-CSF)-induced signaling, c
      Src is central to osteoclast activity, but not differentiation. We find Lyn,
      another member of Src family kinases (SFK) is, in contrast, a negative regulator
      of osteoclastic bone resorption. The absence of Lyn enhances receptor activator
      of NF-kappaB ligand (RANKL)-mediated differentiation of osteoclast precursors
      without affecting proliferation and survival, while its overexpression decreases
      osteoclast formation. In further contrast to c-Src, Lyn deficiency does not
      impact the activity of the mature cell. Reflecting increased osteoclast
      development in vitro, Lyn-/- mice undergo accelerated osteoclastogenesis and bone
      loss, in vivo, in response to RANKL. Mechanistically, Lyn forms a complex with
      receptor activator of NF-kappaB (RANK), the tyrosine phosphatase, SHP-1, and the
      adapter protein, Grb2-associated binder 2 (Gab2). Upon RANKL exposure, Gab2
      phosphorylation, JNK, and NF-kappaB activation are enhanced in Lyn-/-
      osteoclasts, all critical events in osteoclast development. We therefore
      establish that Lyn regulates osteoclast formation and does it in a manner
      antithetical to that of c-Src. The most pragmatic aspect of our findings is that
      successful therapeutic inhibition of c-Src, in the context of the osteoclast,
      will require its stringent targeting.

PMID- 19171908
TI  - Demographic models and IPCC climate projections predict the decline of an emperor
      penguin population.
AB  - Studies have reported important effects of recent climate change on Antarctic
      species, but there has been to our knowledge no attempt to explicitly link those
      results to forecasted population responses to climate change. Antarctic sea ice
      extent (SIE) is projected to shrink as concentrations of atmospheric greenhouse
      gases (GHGs) increase, and emperor penguins (Aptenodytes forsteri) are extremely
      sensitive to these changes because they use sea ice as a breeding, foraging and
      molting habitat. We project emperor penguin population responses to future sea
      ice changes, using a stochastic population model that combines a unique long-term
      demographic dataset (1962-2005) from a colony in Terre Adelie, Antarctica and
      projections of SIE from General Circulation Models (GCM) of Earth's climate
      included in the most recent Intergovernmental Panel on Climate Change (IPCC)
      assessment report. We show that the increased frequency of warm events associated
      with projected decreases in SIE will reduce the population viability. The
      probability of quasi-extinction (a decline of 95% or more) is at least 36% by
      2100. The median population size is projected to decline from approximately 6,000
      to approximately 400 breeding pairs over this period. To avoid extinction,
      emperor penguins will have to adapt, migrate or change the timing of their growth
      stages. However, given the future projected increases in GHGs and its effect on
      Antarctic climate, evolution or migration seem unlikely for such long lived
      species at the remote southern end of the Earth.

PMID- 19171909
TI  - WiFi networks and malware epidemiology.
AB  - In densely populated urban areas WiFi routers form a tightly interconnected
      proximity network that can be exploited as a substrate for the spreading of
      malware able to launch massive fraudulent attacks. In this article, we consider
      several scenarios for the deployment of malware that spreads over the wireless
      channel of major urban areas in the US. We develop an epidemiological model that
      takes into consideration prevalent security flaws on these routers. The spread of
      such a contagion is simulated on real-world data for georeferenced wireless
      routers. We uncover a major weakness of WiFi networks in that most of the
      simulated scenarios show tens of thousands of routers infected in as little as 2
      weeks, with the majority of the infections occurring in the first 24-48 h. We
      indicate possible containment and prevention measures and provide computational
      estimates for the rate of encrypted routers that would stop the spreading of the
      epidemics by placing the system below the percolation threshold.

PMID- 19171910
TI  - Evolutionary tradeoffs for nitrogen allocation to photosynthesis versus cell
      walls in an invasive plant.
AB  - Many studies have shown that individuals from invasive populations of many
      different plant species grow larger than individuals from native populations and
      that this difference has a genetic basis. This increased vigor in invasive
      populations is thought to be due to life history tradeoffs, in which selection
      favors the loss of costly defense traits, thereby freeing resources that can be
      devoted to increased growth or fecundity. Despite the theoretical importance of
      such allocation shifts for invasions, there have been no efforts to understand
      apparent evolutionary shifts in defense-growth allocation mechanistically.
      Reallocation of nitrogen (N) to photosynthesis is likely to play a crucial role
      in any growth increase; however, no study has been conducted to explore potential
      evolutionary changes in N allocation of introduced plants. Here, we show that
      introduced Ageratina adenophora, a noxious invasive plant throughout the
      subtropics, appears to have evolved increased N allocation to photosynthesis
      (growth) and reduced allocation to cell walls, resulting in poorer structural
      defenses. Our results provide a potential mechanism behind the commonly observed
      and genetically based increase in plant growth and vigor when they are introduced
      to new ranges.

PMID- 19171911
TI  - Varicella reactivation presenting as shingles and aseptic meningitis in an
      immunocompetent 11-year-old boy.

PMID- 19171912
TI  - Identifying previous sports injury among high school athletes.

PMID- 19171913
TI  - Staged introduction of antiretroviral therapy into a family with multiple HIV
      infected members.
AB  - Children and families bear a significant burden of human immunodeficiency virus
      disease globally, particularly in sub-Saharan Africa. Care of severely affected
      families can be adversely impacted by high medication burdens and overwhelmed
      caregivers, who themselves may be human immunodeficiency virus infected. Family
      centered care involving joint clinic days, treatment preparation, adherence
      counseling, and community-based follow-up may improve the care of family units.
      We describe the successful treatment of a single family composed of 6 infected
      members living in a rural African setting.

PMID- 19171914
TI  - Developing countries need better antiretroviral drugs.

PMID- 19171915
TI  - Has prolactin a role in the hypogonadal status of HIV-infected patients?
AB  - Most cases of hypogonadism in human immunodeficiency virus (HIV) infection are of
      hypophyseal- hypothalamic origin, and hyperprolactinemia, also commonly observed
      in HIV-infected patients, may cause hypogonadism. We studied 188 HIV-infected men
      who had simultaneous determinations of gonadal and hypophyseal hormones, and we
      found that prolactin levels were independently predictive of hypogonadism in
      multivariate analysis.

PMID- 19171916
TI  - The use of darunavir/ritonavir as intensification in low viremic HIV-infected
      patients treated with boosted protease inhibitor-containing regimens.

PMID- 19171917
TI  - A fluorescence lifetime-based assay for protease inhibitor profiling on human
      kallikrein 7.
AB  - Fluorescence lifetime is an intrinsic parameter describing the fluorescence
      process. Changes in the fluorophore's physicochemical environment can lead to
      changes in the fluorescence lifetime. When used as the readout in biological
      assays, it is thought to deliver superior results to conventional optical
      readouts. Hence it has the potential to replace readout technologies currently
      established in drug discovery such as absorption, luminescence or fluorescence
      intensity. Here we report the development of an activity assay for human
      kallikrein 7, a serine protease involved in skin diseases. As a probe, we have
      selected a blue-fluorescent acridone dye, featuring a remarkably long lifetime
      that can be quenched by either of the 2 natural amino acids, tyrosine and
      tryptophan. Incorporating this probe and 1 of the quenching amino acids on either
      side of the scissile bond of the substrate peptide enables us to monitor the
      enzymatic activity by quantifying the increase in the fluorescence lifetime
      signal. A systematic investigation of substrate structures has led to a
      homogenous, microplate-based, compound profiling assay that yields inhibitory
      constants down into the single-digit nanomolar range. This type of assay has now
      been added to our standard portfolio of screening techniques, and is routinely
      used for compound profiling.

PMID- 19171918
TI  - Development and validation of a higher throughput screening approach to
      genotoxicity testing using the GADD45a-GFP GreenScreen HC assay.
AB  - There is a pressing need to develop rapid yet accurate screening assays for the
      identification of genotoxic liability and for early hazard assessment in drug
      discovery. The GADD45a-GFP human cell-based genotoxicity assay (GreenScreen HC)
      has been reformatted to test 12 compounds per 96-well microplate in a higher
      throughput, automated screening mode and the protocol applied to the analysis of
      1266 diverse, pharmacologically active compounds. Testing from a fixed starting
      concentration of 100 AmicroM and over 3 serial dilutions, the hit rates for
      genotoxicity (7.3%) and cytotoxicity (33%) endpoints of the assay have been
      determined in a much wider chemical space than previously reported. The degree of
      interference from color, autofluorescence, and low solubility has also been
      assessed. The assay results have been compared to an in silico approach to
      genotoxicity assessment using Derek for Windows software. Where carcinogenicity
      data were available, GreenScreen HC demonstrated a higher specificity than in
      silico methods while identifying genotoxic species that were not highlighted for
      genotoxic liability in structure-activity relationship software. Higher
      throughput screening from a fixed, low concentration reduces sensitivity to less
      potent genotoxins, but the maintenance of the previously reported high
      specificity is essential in early hazard assessment where misclassification can
      lead to the needless rejection of potentially useful compounds in drug
      development.

PMID- 19171919
TI  - A high-throughput ligand competition binding assay for the androgen receptor and
      other nuclear receptors.
AB  - Standardized, automated ligand-binding assays facilitate evaluation of endocrine
      activities of environmental chemicals and identification of antagonists of
      nuclear receptor ligands. Many current assays rely on fluorescently labeled
      ligands that are significantly different from the native ligands. The authors
      describe a radiolabeled ligand competition scintillation proximity assay (SPA)
      for the androgen receptor (AR) using Ni-coated 384-well FlashPlates and liganded
      AR-LBD protein. This highly reproducible, low-cost assay is well suited for
      automated high-throughput screening. In addition, the authors show that this
      assay can be adapted to measure ligand affinities for other nuclear receptors
      (peroxisome proliferation-activated receptor gamma, thyroid receptors alpha and
      beta).

PMID- 19171920
TI  - Characterizing cannabinoid CB2 receptor ligands using DiscoveRx PathHunter beta
      arrestin assay.
AB  - The authors have characterized a set of cannabinoid CB(2) receptor ligands,
      including triaryl bis sulfone inverse agonists, in a cell-based receptor/beta
      arrestin interaction assay (DiscoveRx PathHunter). The results were compared with
      results using a competitive ligand binding assay, and with effects on forskolin
      stimulated cAMP levels (PerkinElmer LANCE). The authors show good correlation
      between the 3 assay systems tested, with the beta-arrestin protein
      complementation assay exhibiting a more robust signal than the cAMP assay for
      cannabinoid CB(2) agonists. Further assay validation shows that DiscoveRx
      PathHunter HEK293 CB(2) beta-arrestin assay can be carried out from cryopreserved
      cell suspensions, eliminating variations caused by the need for multiple cell
      pools during live cell screening campaigns. These results, and the authors'
      results evaluating a test set of random library compounds, validate the use of
      ligand-induced interaction between the human cannabinoid CB(2) receptor and beta
      arrestin as an appropriate and valuable screening platform for compounds specific
      for the cannabinoid CB(2) receptor.

PMID- 19171921
TI  - Comparison of variability and sensitivity between nuclear translocation and
      luciferase reporter gene assays.
AB  - High-content screening (HCS), a technology based on subcellular imaging by
      automated microscopy and sophisticated image analysis, has emerged as an
      important platform in small-molecule screening for early drug discovery. To
      validate a subcellular imaging assay for primary screening campaigns, an HCS
      assay was compared with a non-image-based readout in terms of variability and
      sensitivity. A study was performed monitoring the accumulation of the forkhead
      transcription factor of the O subfamily (FOXO3a) coupled with green fluorescent
      protein in the nucleus of human osteosarcoma (U-2 OS) cells. In addition, the
      transcription of a luciferase gene coupled with a FOXO3a-responsive promoter was
      monitored. This report demonstrates that both assay formats show good
      reproducibility in primary and concentration response screening despite
      differences in statistical assay quality. In primary screening, the correlation
      of compound activity between the 2 assays was low, in contrast to the good
      correlation of the IC(50) values of confirmed compounds. Furthermore, the high
      content imaging assay showed a mean shift of 2.63-fold in IC(50) values compared
      with the reporter gene assay. No chemical scaffold was specifically found with 1
      of the technologies only, however these results validate the HCS technology
      against established assays for screening of new molecular entities.

PMID- 19171922
TI  - Process validation and screen reproducibility in high-throughput screening.
AB  - The use of large-scale compound screening has become a key component of drug
      discovery projects in both the pharmaceutical and the biotechnological
      industries. More recently, these activities have also been embraced by the
      academic community as a major tool for chemical genomic activities. High
      throughput screening (HTS) activities constitute a major step in the initial drug
      discovery efforts and involve the use of large quantities of biological reagents,
      hundreds of thousands to millions of compounds, and the utilization of expensive
      equipment. All these factors make it very important to evaluate in advance of the
      HTS campaign any potential issues related to reproducibility of the
      experimentation and the quality of the results obtained at the end of these very
      costly activities. In this article, the authors describe how GlaxoSmithKline
      (GSK) has addressed the need of a true validation of the HTS process before
      embarking in full HTS campaigns. They present 2 different aspects of the so
      called validation process: (1) optimization of the HTS workflow and its
      validation as a quality process and (2) the statistical evaluation of the HTS,
      focusing on the reproducibility of results and the ability to distinguish active
      from nonactive compounds in a vast collection of samples. The authors describe a
      variety of reproducibility indexes that are either innovative or have been
      adapted from generic medical diagnostic screening strategies. In addition, they
      exemplify how these validation tools have been implemented in a number of case
      studies at GSK.

PMID- 19171923
TI  - Isolation of novel EGFR-specific VHH domains.
AB  - Epidermal growth factor receptor (EGFR) is overexpressed or mutated in a high
      percentage of tumors. EGFR has long been considered a promising target for cancer
      diagnostic and therapeutic applications. However, monoclonal antibodies and other
      large antibody constructs diffuse into tumors slowly, limiting their efficacy. To
      develop lower molecular weight probes for EGFR and other tumor cell receptors,
      the authors immunized a llama with the extracellular domains (ECDs) of EGFR and
      an oncogenic mutant receptor, EGFRvIII, and with extracts of tumor cell lines.
      From the immune repertoire of the llama, the authors constructed a heavy chain
      variable domain (VHH domain)-phage library. At approximately 16 kDa, the VHH
      domain is a tenth of the size of a monoclonal antibody and is the smallest
      antibody fragment that retains specificity. By affinity selection from this
      library, the authors isolated many VHH domains with specificity for EGFR. The VHH
      domains bind to whole cells expressing the receptor but not to control cells
      lacking the receptor and can immunoprecipitate EGFR from cell lysates. Some VHH
      domains have cross-specificity with existing anti-EGFR monoclonal antibodies and
      have reasonably high (nM) affinities. The llama-VHH domain library is also
      potentially a rich source of targeting agents directed toward other tumor cell
      receptors.

PMID- 19171924
TI  - Optimizing the expression of recombinant alphabetagamma GABAA receptors in HEK293
      cells for high-throughput screening.
AB  - Despite being important clinical targets, it is not straightforward to reliably
      express recombinant trimeric alphabetagamma GABA-A receptors (GABA(A)Rs) for high
      throughput screening. This study therefore sought to devise a simple and reliable
      means of transiently expressing alpha1beta1gamma1 and alpha1beta1gamma2 GABA(A)Rs
      in HEK293 cells. Expression efficiencies resulting from 5 different transfection
      strategies were assessed by flow cytometry and pharmacological analysis using an
      anion-sensitive yellow fluorescent protein-based assay. PolyFect and Effectene,
      employed according to the manufacturers' instructions, conferred the strongest
      and most reliable expression of trimeric alphabetagamma GABA(A)Rs. Functional
      analysis via the yellow fluorescent protein assay revealed dramatic differences
      in the pharmacological properties of gamma1- and gamma2-containing receptors,
      consistent with previous electrophysiological characterizations. The authors
      conclude that this method of expressing and screening recombinant GABA(A)Rs
      provides an effective means of discovering novel GABA(A)R modulators for use as
      therapeutic lead compounds and pharmacological probes.

PMID- 19171925
TI  - Genome-wide linkage analysis with clustered SNP markers.
AB  - Single nucleotide polymorphisms (SNPs) have recently replaced microsatellites as
      the genetic markers of choice in linkage analysis, primarily because they are
      more abundant and the genotypes more amenable for automatic calling. One of the
      most recently launched linkage mapping sets (LMS) is the Applied Biosystems Human
      LMS 4K, which is a genome-wide linkage set based on the SNPlex technology and the
      use of clustered SNPs. In this article the authors report on their experience
      with this set and the associated genotyping software GeneMapper version 4.0,
      which they have used for linkage analyses in 17 moderate to large families with
      assumed monogenic disease. For comparison of methods, they also performed a
      genome-wide linkage analysis in 1 of the 17 families using the Affymetrix
      GeneChip Human Mapping 10K 2.0 array. The conclusion is that both methods
      performed technically well, with high call rates and comparable and low rates of
      Mendelian inconsistencies. However, genotyping is less automated in GeneMapper
      version 4.0 than in the Affymetrix software and thus more time consuming.

PMID- 19171926
TI  - A comparative analysis of acute-phase proteins as inflammatory biomarkers in
      preclinical toxicology studies: implications for preclinical to clinical
      translation.
AB  - Recently, in early clinical development, a few biologics and small molecules
      intended as antitumor or anti-inflammatory agents have caused a severe adverse
      pro-inflammatory systemic reaction also known as systemic inflammatory response
      syndrome (SIRS). This toxicity could result from expected pharmacological effects
      of a therapeutic antibody and/or from interaction with antigens expressed on
      cells/tissues other than the intended target. Clinical monitoring of SIRS is
      challenging because of the narrow diagnostic window to institute a successful
      intervening therapeutic strategy prior to acute circulatory collapse.
      Furthermore, for these classes of therapeutic agents, studies in animals have low
      predictive ability to identify potential human hazards. In vitro screens with
      human cells, though promising, need further development. Therefore,
      identification of improved preclinical diagnostic markers of SIRS will enable
      clinicians to select applicable markers for clinical testing and avoid
      potentially catastrophic events. There is limited preclinical toxicology data
      describing the interspecies performance of acute-phase proteins because the
      response time, type, and duration of major acute-phase proteins vary
      significantly between species. This review will attempt to address this
      intellectual gap, as well as the use and applicability of acute-phase proteins as
      preclinical to clinical translational biomarkers of SIRS.

PMID- 19171927
TI  - The role of haptic macrophages in regulation of idiosyncratic drug reactions.
AB  - Idiosyncratic drug reactions (IDR) account for approximately 6%-10% of all
      adverse drug reactions. The unpredictable and serious nature of these reactions
      makes them a significant economic burden and safety concern to the health care
      community and the pharmaceutical industry. Clinical and laboratory evidence
      suggests that adverse immune responses against drug-protein adducts play a role
      in the pathogenesis of IDR. However, it remains unclear why only a small
      percentage of patients are susceptible to developing these reactions. We
      hypothesized that most patients develop immunological tolerance against drug
      protein adducts as a default mechanism, and that IDRs can only occur when this
      tolerance is deficient or abrogated in susceptible individuals. Using a murine
      model of 2,4-dinitrochlorobenzene (DNCB)-induced delayed type hypersensitivity
      (DTH) reaction, our previously published data demonstrated that intravenous
      pretreatment of mice with dinitrophenyl-bovine serum albumin (DNP-BSA) induced
      immunological tolerance to subsequent DNCB sensitization, and that hepatic
      macrophages (Kupffer cells, KC) played an important role in mediating such
      tolerance. Further mechanistic investigation revealed that KC, acting as
      incompetent antigen-presenting cells, cannot elicit strong T cell reactions, and
      that they actively suppress T cell activation through production of
      prostaglandins. These findings suggest that KCs may play a critical role in
      regulating immune reactions within the liver and contributing to liver-mediated
      systemic immune tolerance.

PMID- 19171929
TI  - Preclinical support for combination therapy in the treatment of autoimmunity with
      atacicept.
AB  - Atacicept, a fully human recombinant fusion protein that blocks the activity of
      BLyS (B-Lymphocyte Stimulator) and APRIL (a proliferation-inducing ligand), is
      undergoing clinical evaluation in B-cell-mediated diseases, including autoimmune
      disorders. Nonclinical studies in mice and cynomolgus monkeys demonstrate dose
      dependent, reversible decreases in circulating Ig concentrations and reductions
      in mature B cells in the peripheral blood and lymphoid tissues. However, the
      combination of atacicept with purine synthesis inhibitors (e.g., mycophenolate
      mofetil [MMF]) and anti-B-cell monoclonal therapy (e.g., rituximab) has not been
      evaluated. Atacicept does not augment hematological toxicities associated with
      MMF, including anemia or thrombocytopenia. Combination of atacicept with MMF or
      rituximab reduced B cells in the periphery (MMF) or tissues (MMF and rituximab)
      further than did monotherapy, as was the case with atacicept-MMF combination
      therapy and serum Ig concentrations. Overall, atacicept appears to augment the
      pharmacologic activity toward B cells of current immunosuppressive therapies
      without increasing the hematological toxicities associated with MMF. Enhanced
      reduction in B cells and Ig concentrations associated with atacicept combination
      therapy may increase therapeutic activity or allow dose reduction in autoimmune
      patients. Findings from nonclinical safety studies support clinical evaluation of
      atacicept combination therapies.

PMID- 19171928
TI  - The role of protease inhibitors in the pathogenesis of HIV-associated
      lipodystrophy: cellular mechanisms and clinical implications.
AB  - Metabolic complications associated with HIV infection and treatment frequently
      present as a relative lack of peripheral adipose tissue associated with
      dyslipidemia and insulin resistance. In this review we explain the connection
      between abnormalities of intermediary metabolism, observed either in vitro or in
      vivo, and this group of metabolic effects. We review molecular mechanisms by
      which the HIV protease inhibitor (PI) class of drugs may affect the normal
      stimulatory effect of insulin on glucose and fat storage. We then propose that
      both chronic inflammation from HIV infection and treatment with some drugs in
      this class trigger cellular homeostatic stress responses with adverse effects on
      intermediary metabolism. The physiologic outcome is such that total adipocyte
      storage capacity is decreased, and the remaining adipocytes resist further fat
      storage. The excess circulating and dietary lipid metabolites, normally
      "absorbed" by adipose tissue, are deposited ectopically in lean (muscle and
      liver) tissue, where they impair insulin action. This process leads to a
      pathologic cycle of lipotoxicity and lipoatrophy and a clinical phenotype of body
      fat distribution with elevated waist-to-hip ratio similar to the metabolic
      syndrome.

PMID- 19171930
TI  - Immunotoxicity and environment: immunodysregulation and systemic inflammation in
      children.
AB  - Environmental pollutants, chemicals, and drugs have an impact on children's
      immune system development. Mexico City (MC) children exposed to significant
      concentrations of air pollutants exhibit chronic respiratory inflammation,
      systemic inflammation, neuroinflammation, and cognitive deficits. We tested the
      hypothesis that exposure to severe air pollution plays a role in the immune
      responses of asymptomatic, apparently healthy children. Blood measurements for
      markers of immune function, inflammatory mediators, and molecules interacting
      with the lipopolysaccharide recognition complex were obtained from two cohorts of
      matched children (aged 9.7 +/- 1.2 years) from southwest Mexico City (SWMC) (n =
      66) and from a control city (n = 93) with criteria pollutant levels below current
      standards. MC children exhibited significant decreases in the numbers of natural
      killer cells (p = .003) and increased numbers of mCD14+ monocytes (p < .001) and
      CD8+ cells (p = .02). Lower concentrations of interferon gamma (p = .009) and
      granulocyte-macrophage colony-stimulating factor (p < .001), an endotoxin
      tolerance-like state, systemic inflammation, and an anti-inflammatory response
      were also present in the highly exposed children. C-reactive protein and the
      prostaglandin E metabolite levels were positively correlated with twenty-four-
      and forty-eight-hour cumulative concentrations of PM(2.5). Exposure to urban air
      pollution is associated with immunodysregulation and systemic inflammation in
      children and is a major health threat.

PMID- 19171931
TI  - The liver toxicity biomarker study: phase I design and preliminary results.
AB  - Drug-induced liver injury (DILI) is the primary adverse event that results in
      withdrawal of drugs from the market and a frequent reason for the failure of drug
      candidates in development. The Liver Toxicity Biomarker Study (LTBS) is an
      innovative approach to investigate DILI because it compares molecular events
      produced in vivo by compound pairs that (a) are similar in structure and
      mechanism of action, (b) are associated with few or no signs of liver toxicity in
      preclinical studies, and (c) show marked differences in hepatotoxic potential.
      The LTBS is a collaborative preclinical research effort in molecular systems
      toxicology between the National Center for Toxicological Research and BG
      Medicine, Inc., and is supported by seven pharmaceutical companies and three
      technology providers. In phase I of the LTBS, entacapone and tolcapone were
      studied in rats to provide results and information that will form the foundation
      for the design and implementation of phase II. Molecular analysis of the rat
      liver and plasma samples combined with statistical analyses of the resulting
      datasets yielded marker analytes, illustrating the value of the broad-spectrum,
      molecular systems analysis approach to studying pharmacological or toxicological
      effects.

PMID- 19171932
TI  - AMP-activated protein kinase phosphorylates R5/PTG, the glycogen targeting
      subunit of the R5/PTG-protein phosphatase 1 holoenzyme, and accelerates its down
      regulation by the laforin-malin complex.
AB  - R5/PTG is one of the glycogen targeting subunits of type 1 protein phosphatase, a
      master regulator of glycogen synthesis. R5/PTG recruits the phosphatase to the
      places where glycogen synthesis occurs, allowing the activation of glycogen
      synthase and the inactivation of glycogen phosphorylase, thus increasing glycogen
      synthesis and decreasing its degradation. In this report, we show that the
      activity of R5/PTG is regulated by AMP-activated protein kinase (AMPK). We
      demonstrate that AMPK interacts physically with R5/PTG and modifies its basal
      phosphorylation status. We have also mapped the major phosphorylation sites of
      R5/PTG by mass spectrometry analysis, observing that phosphorylation of Ser-8 and
      Ser-268 increased upon activation of AMPK. We have recently described that the
      activity of R5/PTG is down-regulated by the laforin-malin complex, composed of a
      dual specificity phosphatase (laforin) and an E3-ubiquitin ligase (malin). We now
      demonstrate that phosphorylation of R5/PTG at Ser-8 by AMPK accelerates its
      laforin/malin-dependent ubiquitination and subsequent proteasomal degradation,
      which results in a decrease of its glycogenic activity. Thus, our results define
      a novel role of AMPK in glycogen homeostasis.

PMID- 19171933
TI  - {beta}-Arrestin-2 Mediates Anti-apoptotic Signaling through Regulation of BAD
      Phosphorylation.
AB  - beta-Arrestins, originally discovered as terminators of G protein-coupled
      receptor signaling, have more recently been appreciated to also function as
      signal transducers in their own right, although the consequences for cellular
      physiology have not been well understood. Here we demonstrate that beta-arrestin
      2 mediates anti-apoptotic cytoprotective signaling stimulated by a typical 7
      transmembrane receptor the angiotensin ATII 1A receptor, expressed endogenously
      in rat vascular smooth muscle cells or by transfection in HEK-293 cells. Receptor
      stimulation leads to concerted activation of two pathways, ERK/p90RSK and
      PI3K/AKT, which converge to phosphorylate and inactivate the pro-apoptotic
      protein BAD. Anti-apoptotic effects as well as pathway activities can be
      stimulated by an angiotensin analog (SII), which has been previously shown to
      activate beta-arrestin but not G protein-dependent signaling, and are abrogated
      by beta-arrestin-2 small interfering RNA. These findings establish a key role for
      beta-arrestin-2 in mediating cellular cytoprotective functions by a 7
      transmembrane receptor and define the biochemical pathways involved.

PMID- 19171934
TI  - Luciferase fragment complementation imaging of conformational changes in the
      epidermal growth factor receptor.
AB  - Crystal structures of the epidermal growth factor (EGF) receptor suggest that its
      activation is associated with extensive conformational changes in both the
      extracellular and intracellular domains. However, evidence of these structural
      dynamics in intact cells has been lacking. Here we use luciferase complementation
      imaging to follow EGF-induced conformational changes in its receptor in real time
      in live cells. When the luciferase fragments are fused to the C terminus of an
      EGF receptor lacking the cytoplasmic domain, EGF stimulates a rapid increase in
      luciferase activity, consistent with ligand-induced receptor dimerization.
      However, when the luciferase fragments are fused to the C terminus of the full
      length receptor, EGF induces a rapid but transient decrease in luciferase
      activity. The decrease requires tyrosine kinase activity, whereas the subsequent
      recovery requires MAP kinase activity. Our data demonstrate the utility of the
      luciferase system for in vivo imaging changes in EGF receptor dimerization and
      conformation. They also identify two sequential ligand-induced conformational
      changes in the EGF receptor.

PMID- 19171935
TI  - Structure and function of an NADPH-cytochrome P450 oxidoreductase in an open
      conformation capable of reducing cytochrome P450.
AB  - NADPH-cytochrome P450 oxidoreductase (CYPOR) catalyzes the transfer of electrons
      to all known microsomal cytochromes P450. A CYPOR variant, with a 4-amino acid
      deletion in the hinge connecting the FMN domain to the rest of the protein, has
      been crystallized in three remarkably extended conformations. The variant donates
      an electron to cytochrome P450 at the same rate as the wild-type, when provided
      with sufficient electrons. Nevertheless, it is defective in its ability to
      transfer electrons intramolecularly from FAD to FMN. The three extended CYPOR
      structures demonstrate that, by pivoting on the C terminus of the hinge, the FMN
      domain of the enzyme undergoes a structural rearrangement that separates it from
      FAD and exposes the FMN, allowing it to interact with its redox partners. A
      similar movement most likely occurs in the wild-type enzyme in the course of
      transferring electrons from FAD to its physiological partner, cytochrome P450. A
      model of the complex between an open conformation of CYPOR and cytochrome P450 is
      presented that satisfies mutagenesis constraints. Neither lengthening the linker
      nor mutating its sequence influenced the activity of CYPOR. It is likely that the
      analogous linker in other members of the diflavin family functions in a similar
      manner.

PMID- 19171936
TI  - The glutathione system of Aspergillus nidulans involves a fungus-specific
      glutathione S-transferase.
AB  - The tripeptide glutathione is involved in cellular defense mechanisms for
      xenobiotics and reactive oxygen species. This study investigated glutathione
      dependent mechanisms in the model organism Aspergillus nidulans. A recombinant
      dimeric protein of A. nidulans glutathione reductase (GR) contained FAD and
      reduced oxidized glutathione (GSSG) using NADPH as an electron donor. A deletion
      strain of the GR gene (glrA) accumulated less intracellular reduced glutathione
      (GSH), indicating that the fungal GR contributes to GSSG reduction in vivo.
      Growth of the deletion strain of glrA was temperature-sensitive, and this
      phenotype was suppressed by adding GSH to the medium. The strain subsequently
      accumulated more intracellular superoxide, and cell-free respiration activity was
      partly defective. Growth of the strain decreased in the presence of oxidants,
      which induced glrA expression 1.5-6-fold. These results indicated that the fungal
      glutathione system functions as an antioxidant mechanism in A. nidulans. Our
      findings further revealed an initial proteomic differential display on GR
      depleted and wild type strains. Up-regulation of thioredoxin reductase,
      peroxiredoxins, catalases, and cytochrome c peroxidase in the glrA-deletion
      strain revealed interplay between the glutathione system and both the thioredoxin
      system and hydrogen peroxide defense mechanisms. We also identified a
      hypothetical, up-regulated protein in the GR-depleted strains as glutathione S
      transferase, which is unique among Ascomycetes fungi.

PMID- 19171937
TI  - Aromatic Residues {epsilon}Trp-55 and {delta}Trp-57 and the Activation of
      Acetylcholine Receptor Channels.
AB  - The two transmitter binding sites of the neuromuscular acetylcholine (ACh)
      receptor channel contain several aromatic residues, including a tryptophan
      located on the complementary, negative face of each binding pocket. These two
      residues, Trp-55 in the epsilon subunit and Trp-57 in the delta subunit, were
      mutated (AEFHILRVY), and for most constructs the rate constants for acetylcholine
      binding and channel gating were estimated by using single channel kinetic
      analyses. The rate constants for unliganded channel opening and closing were also
      estimated for some mutants. From these measurements we calculated all of the
      equilibrium constants of the "allosteric" cycle as follows: diliganded gating,
      unliganded gating, dissociation from the C(losed) conformation, and dissociation
      from the O(pen) conformation. The results indicate the following. (i) These
      aromatic side chains play a relatively minor role in ACh receptor channel
      activation. (ii) The main consequence of mutations is to reduce the affinity of
      the O conformation of the binding site for ACh, with the effect being greater at
      the epsilon subunit. (iii) In epsilon (but not delta) the aromatic nature of the
      side chain is important in determining affinity, to a slightly greater degree in
      the O conformation. Phi value analyses (of both tryptophan residues) show Phi
      approximately 1 for both the ACh binding and diliganded gating reactions. (iv)
      This suggests that the structural boundaries of the dynamic elements of the
      gating conformational change may not be subunit-delimited, and (v) the mutated
      tryptophan residues experience energy changes that occur relatively early in both
      the ligand-binding and channel-gating reactions.

PMID- 19171938
TI  - Functional Interactions between Distinct Sodium Channel Cytoplasmic Domains
      through the Action of Calmodulin.
AB  - Sodium channels are fundamental signaling molecules in excitable cells, and are
      molecular targets for local anesthetic agents and intracellular free Ca(2+)
      ([Ca(2+)](i)). Two regions of Na(V)1.5 have been identified previously as
      [Ca(2+)](i)-sensitive modulators of channel inactivation. These include a C
      terminal IQ motif that binds calmodulin (CaM) in different modes depending on
      Ca(2+) levels, and an immediately adjacent C-terminal EF-hand domain that
      directly binds Ca(2+). Here we show that a mutation of the IQ domain (A1924T;
      Brugada Syndrome) that reduces CaM binding stabilizes Na(V)1.5 inactivation,
      similarly and more extensively than even reducing [Ca(2+)](i). Because the DIII
      DIV linker is an essential structure in Na(V)1.5 inactivation, we evaluated this
      domain for a potential CaM binding interaction. We identified a novel CaM binding
      site within the linker, validated its interaction with CaM by NMR spectroscopy,
      and revealed its micromolar affinity by isothermal titration calorimetry.
      Mutation of three consecutive hydrophobic residues (Phe(1520)-Ile(1521)
      Phe(1522)) to alanines in this CaM-binding domain recapitulated the
      electrophysiology phenotype observed with mutation of the C-terminal IQ domain:
      Na(V)1.5 inactivation was stabilized; moreover, mutations of either CaM-binding
      domain abolish the well described stabilization of inactivation by lidocaine. The
      direct physical interaction of CaM with the C-terminal IQ domain and the DIII-DIV
      linker, combined with the similarity in phenotypes when CaM-binding sites in
      either domain are mutated, suggests these cytoplasmic structures could be
      functionally coupled through the action of CaM. These findings have bearing upon
      Na(+) channel function in genetically altered channels and under pathophysiologic
      conditions where [Ca(2+)](i) impacts cardiac conduction.

PMID- 19171939
TI  - Elaboration, diversification and regulation of the Sir1 family of silencing
      proteins in Saccharomyces.
AB  - Heterochromatin renders domains of chromosomes transcriptionally silent and, due
      to clonal variation in its formation, can generate heritably distinct populations
      of genetically identical cells. Saccharomyces cerevisiae's Sir1 functions
      primarily in the establishment, but not the maintenance, of heterochromatic
      silencing at the HMR and HML loci. In several Saccharomyces species, we
      discovered multiple paralogs of Sir1, called Kos1-Kos4 (Kin of Sir1). The Kos and
      Sir1 proteins contributed partially overlapping functions to silencing of both
      cryptic mating loci in S. bayanus. Mutants of these paralogs reduced silencing at
      HML more than at HMR. Most genes of the SIR1 family were located near telomeres,
      and at least one paralog was regulated by telomere position effect. In S.
      cerevisiae, Sir1 is recruited to the silencers at HML and HMR via its ORC
      interacting region (OIR), which binds the bromo adjacent homology (BAH) domain of
      Orc1. Zygosaccharomyces rouxii, which diverged from Saccharomyces after the
      appearance of the silent mating cassettes, but before the whole-genome
      duplication, contained an ortholog of Kos3 that was apparently the archetypal
      member of the family, with only one OIR. In contrast, a duplication of this
      domain was present in all orthologs of Sir1, Kos1, Kos2, and Kos4. We propose
      that the functional specialization of Sir3, itself a paralog of Orc1, as a
      silencing protein was facilitated by the tandem duplication of the OIR domain in
      the Sir1 family, allowing distinct Sir1-Sir3 and Sir1-Orc1 interactions through
      OIR-BAH domain interactions.

PMID- 19171940
TI  - Drosophila convoluted/dALS is an essential gene required for tracheal tube
      morphogenesis and apical matrix organization.
AB  - Insulin-like growth factors (IGFs) control cell and organism growth through
      evolutionarily conserved signaling pathways. The mammalian acid-labile subunit
      (ALS) is a secreted protein that complexes with IGFs to modulate their activity.
      Recent work has shown that a Drosophila homolog of ALS, dALS, can also complex
      with and modulate the activity of a Drosophila IGF. Here we report the first
      mutations in the gene encoding dALS. Unexpectedly, we find that these mutations
      are allelic to a previously described mutation in convoluted (conv), a gene
      required for epithelial morphogenesis. In conv mutants, the tubes of the
      Drosophila tracheal system become abnormally elongated without altering tracheal
      cell number. conv null mutations cause larval lethality, but do not disrupt
      several processes required for tracheal tube size control, including septate
      junction formation, deposition of a lumenal/apical extracellular matrix, and
      lumenal secretion of Vermiform and Serpentine, two putative matrix-modifying
      proteins. Clearance of lumenal matrix and subcellular localization of clathrin
      also appear normal in conv mutants. However, we show that Conv/dALS is required
      for the dynamic organization of the transient lumenal matrix and normal structure
      of the cuticle that lines the tracheal lumen. These and other data suggest that
      the Conv/dALS-dependent tube size control mechanism is distinct from other known
      processes involved in tracheal tube size regulation. Moreover, we present
      evidence indicating that Conv/dALS has a novel, IGF-signaling independent
      function in tracheal morphogenesis.

PMID- 19171941
TI  - Effects of Wolbachia infection and ovarian tumor mutations on Sex-lethal germline
      functioning in Drosophila.
AB  - Wolbachia is a ubiquitous intracellular endosymbiont of invertebrates.
      Surprisingly, infection of Drosophila melanogaster by this maternally inherited
      bacterium restores fertility to females carrying ovarian tumor (cystocyte
      overproliferation) mutant alleles of the Drosophila master sex-determination
      gene, Sex-lethal (Sxl). We scanned the Drosophila genome for effects of infection
      on transcript levels in wild-type previtellogenic ovaries that might be relevant
      to this suppression of female-sterile Sxl mutants by Wolbachia. Yolk protein gene
      transcript levels were most affected, being reduced by infection, but no genes
      showed significantly more than a twofold difference. The yolk gene effect likely
      signals a small, infection-induced delay in egg chamber maturation unrelated to
      suppression. In a genetic study of the Wolbachia-Sxl interaction, we established
      that germline Sxl controls meiotic recombination as well as cystocyte
      proliferation, but Wolbachia only influences the cystocyte function. In contrast,
      we found that mutations in ovarian tumor (otu) interfere with both Sxl germline
      functions. We were led to otu through characterization of a spontaneous dominant
      suppressor of the Wolbachia-Sxl interaction, which proved to be an otu mutation.
      Clearly Sxl and otu work together in the female germline. These studies of
      meiosis in Sxl mutant females revealed that X chromosome recombination is
      considerably more sensitive than autosomal recombination to reduced Sxl activity.

PMID- 19171942
TI  - Expression of I-CreI endonuclease generates deletions within the rDNA of
      Drosophila.
AB  - The rDNA arrays in Drosophila contain the cis-acting nucleolus organizer regions
      responsible for forming the nucleolus and the genes for the 28S, 18S, and 5.8S/2S
      RNA components of the ribosomes and so serve a central role in protein synthesis.
      Mutations or alterations that affect the nucleolus organizer region have
      pleiotropic effects on genome regulation and development and may play a role in
      genomewide phenomena such as aging and cancer. We demonstrate a method to create
      an allelic series of graded deletions in the Drosophila Y-linked rDNA of
      otherwise isogenic chromosomes, quantify the size of the deletions using real
      time PCR, and monitor magnification of the rDNA arrays as their functions are
      restored. We use this series to define the thresholds of Y-linked rDNA required
      for sufficient protein translation, as well as establish the rate of Y-linked
      rDNA magnification in Drosophila. Finally, we show that I-CreI expression can
      revert rDNA deletion phenotypes, suggesting that double-strand breaks are
      sufficient to induce rDNA magnification.

PMID- 19171943
TI  - Construction of genetic linkage maps and comparative genome analysis of catfish
      using gene-associated markers.
AB  - A genetic linkage map of the channel catfish genome (N=29) was constructed using
      EST-based microsatellite and single nucleotide polymorphism (SNP) markers in an
      interspecific reference family. A total of 413 microsatellites and 125 SNP
      markers were polymorphic in the reference family. Linkage analysis using JoinMap
      4.0 allowed mapping of 331 markers (259 microsatellites and 72 SNPs) to 29
      linkage groups. Each linkage group contained 3-18 markers. The largest linkage
      group contained 18 markers and spanned 131.2 cM, while the smallest linkage group
      contained 14 markers and spanned only 7.9 cM. The linkage map covered a genetic
      distance of 1811 cM with an average marker interval of 6.0 cM. Sex-specific maps
      were also constructed; the recombination rate for females was 1.6 times higher
      than that for males. Putative conserved syntenies between catfish and zebrafish,
      medaka, and Tetraodon were established, but the overall levels of genome
      rearrangements were high among the teleost genomes. This study represents a first
      generation linkage map constructed by using EST-derived microsatellites and SNPs,
      laying a framework for large-scale comparative genome analysis in catfish. The
      conserved syntenies identified here between the catfish and the three model fish
      species should facilitate structural genome analysis and evolutionary studies,
      but more importantly should facilitate functional inference of catfish genes.
      Given that determination of gene functions is difficult in nonmodel species such
      as catfish, functional genome analysis will have to rely heavily on the
      establishment of orthologies from model species.

PMID- 19171945
TI  - Effect of late promoter activity on bacteriophage lambda fitness.
AB  - For many bacteriophages (phages), the proteins responsible for host lysis and
      virion morphogenesis are expressed from the same polycistronic transcript. Such
      an expression pattern can potentially have a pleiotropic effect on the assembly
      rate and lysis time, thus affecting phage fitness. To study the effects of late
      promoter activity on phage life history traits and fitness, we constructed a
      series of isogenic phage lambda strains that differ only in their late promoter
      pR' sequences. The resulting late promoter activities ranged from 6 to 100% of
      the wild type's. The lysis times, burst sizes, and relative fitness were
      empirically determined for these strains. Our results showed that the lysis time
      is more sensitive than the assembly rate to variation in pR' activity. However,
      except for the strain with the lowest activity, the relative fitnesses of all the
      other strains are not significantly different from each other. Ad hoc models
      describing the effects of the late promoter activity on lysis time and assembly
      rate were constructed. The expected phage burst size and fitness curve were
      predicted from these models. Evolution of the late promoter activity was
      discussed in the context of phage life history trait evolution.

PMID- 19171944
TI  - Tools for fungal proteomics: multifunctional neurospora vectors for gene
      replacement, protein expression and protein purification.
AB  - The completion of genome-sequencing projects for a number of fungi set the stage
      for detailed investigations of proteins. We report the generation of versatile
      expression vectors for detection and isolation of proteins and protein complexes
      in the filamentous fungus Neurospora crassa. The vectors, which can be adapted
      for other fungi, contain C- or N-terminal FLAG, HA, Myc, GFP, or HAT-FLAG epitope
      tags with a flexible poly-glycine linker and include sequences for targeting to
      the his-3 locus in Neurospora. To introduce mutations at native loci, we also
      made a series of knock-in vectors containing epitope tags followed by the
      selectable marker hph (resulting in hygromycin resistance) flanked by two loxP
      sites. We adapted the Cre/loxP system for Neurospora, allowing the selectable
      marker hph to be excised by introduction of Cre recombinase into a strain
      containing a knock-in cassette. Additionally, a protein purification method was
      developed on the basis of the HAT-FLAG tandem affinity tag system, which was used
      to purify HETEROCHROMATIN PROTEIN 1 (HP1) and associated proteins from
      Neurospora. As expected on the basis of yeast two-hybrid and co
      immunoprecipitation (Co-IP) experiments, the Neurospora DNA methyltransferase DIM
      2 was found in a complex with HP1. Features of the new vectors allowed for
      verification of an interaction between HP1 and DIM-2 in vivo by Co-IP assays on
      proteins expressed either from their native loci or from the his-3 locus.

PMID- 19171946
TI  - Training with virtual visual feedback to alleviate phantom limb pain.
AB  - BACKGROUND: Performing phantom movements with visual virtual feedback, or mirror
      therapy, is a promising treatment avenue to alleviate phantom limb pain. However
      the effectiveness of this approach appears to vary from one patient to another.
      OBJECTIVE: To assess the individual response to training with visual virtual
      feedback and to explore factors influencing the response to that approach.
      METHODS: Eight male participants with phantom limb pain (PLP) resulting from
      either a traumatic upper limb amputation or a brachial plexus avulsion
      participated in this single case multiple baseline study. Training was performed
      2 times per week for 8 weeks where a virtual image of a missing limb performing
      different movements was presented and the participant was asked to follow the
      movements with his phantom limb. RESULTS: Patients reported an average 38%
      decrease in background pain on a visual analog scale (VAS), with 5 patients out
      of 8 reporting a reduction greater than 30%. This decrease in pain was maintained
      at 4 weeks postintervention in 4 of the 5 participants. No significant
      relationship was found between the long-term pain relief and the duration of the
      deafferentation or with the immediate pain relief during exposure to the
      feedback. CONCLUSIONS: These results support the use of training with virtual
      feedback to alleviate phantom limb pain. Our observations suggest that between
      participant differences in the effectiveness of the treatment might be related
      more to a difference in the susceptibility to the virtual visual feedback, than
      to factors related to the lesion, such as the duration of the deafferentation.

PMID- 19171948
TI  - Sleep enhances off-line spatial and temporal motor learning after stroke.
AB  - BACKGROUND: Individuals with chronic stroke demonstrate sleep-dependent off-line
      motor learning of a continuous tracking task. However, it remains unclear which
      aspects of learned movements are preferentially enhanced by sleep (ie, spatial
      accuracy and/or the time lag of tracking). OBJECTIVE: . The purpose of this study
      was to investigate whether spatial tracking accuracy, temporal tracking accuracy,
      or both are enhanced by sleep during off-line motor learning after stroke.
      METHODS: . Individuals with chronic stroke and control participants either
      practiced a continuous tracking task in the evening and underwent retention
      testing the following morning (sleep groups) or practiced the task in the morning
      and underwent retention testing in the evening (no-sleep groups). RESULTS: .
      Individuals with stroke who slept between practice and retention testing
      demonstrated off-line improvements in both spatial and temporal elements of
      tracking at retention. Participants with a stroke who stayed awake between
      practice and retention testing did not demonstrate off-line improvements in
      either spatial tracking accuracy or the time lag of tracking. Control
      participants did not demonstrate sleep- or time-dependent enhancement of either
      component of the movement task. Time of day of testing was not a factor in
      practice related changes in motor performance. CONCLUSION: This study provides
      the first evidence that sleep enhances motor learning through both improved
      spatial tracking accuracy and anticipation of upcoming movements, as demonstrated
      by a reduction in the time lag of tracking in individuals following stroke. We
      propose that the cerebellum and hippocampus are likely important neural
      correlates associated with sleep-dependent off-line motor skill learning.

PMID- 19171947
TI  - Return of memory and sleep efficiency following moderate to severe closed head
      injury.
AB  - OBJECTIVE: Sleep disturbance is common in the subacute recovery phase following
      brain injury. A previous study from the authors' group found 68% of patients with
      closed head injury (CHI) had disrupted sleep on a rehabilitation unit. In the
      present study, the authors investigated whether improvement in sleep efficiency
      correlates with duration of posttraumatic amnesia (PTA) after CHI. METHODS:
      Fourteen CHI patients were enrolled and followed prospectively. Mechanism of
      injury included motor vehicle accident, fall, and blunt assault. An actigraph was
      placed on each subject's wrist within 72 hours of admission to the rehabilitation
      unit and recorded data for the duration of their stay. A minimum of 7 days of
      continuous actigraphy data was obtained on all subjects. PTA was measured daily
      using the Orientation Log (O-LOG). RESULTS: Seventy-eight percent of subjects had
      mean week-1 sleep efficiency scores of < or = 63%. Patients admitted having
      already cleared PTA had significantly better week-1 sleep efficiency scores than
      those with ongoing amnesia (P = .032). For those patients admitted with ongoing
      PTA, each 10-unit increase in sleep efficiency score correlated with 1 unit
      increase in O-LOG score (P = .056). CONCLUSIONS: Disrupted sleep is common in the
      postacute stage following CHI. Improved sleep efficiency correlates with
      resolution of PTA. Decreased sleep efficiency may negatively affect memory return
      after traumatic brain injury. Actigraphy is uniquely suited to study the sleep
      patterns of these patients.

PMID- 19171949
TI  - Free recall and learning of emotional word lists in very elderly people with and
      without dementia.
AB  - An emotional memory advantage has been found across the life span where recall is
      better for emotional (as opposed to neutral) stimuli. Our goal was to design
      emotionally valent word lists for easy use by practitioners and to test whether
      demented and healthy elderly participants showed an emotional memory advantage
      with these lists. Three new word lists (a positive, a negative, and a neutral
      list) were constructed. Thirty-eight controls, 37 with mild cognitive impairment
      and 20 Alzheimer's dementia participants' free recall was tested. Unsurprisingly,
      controls had better recall overall. Emotionally valent words were recalled better
      in comparison to neutral words in all 3 groups. No recall advantage for positive
      versus negative words emerged. Learning differed among the groups with the
      Alzheimer's dementia participants showing flatter learning curves. The results
      tentatively suggest that emotional memory may stay intact longer but that
      learning of such lists becomes more difficult as dementia progresses.

PMID- 19171950
TI  - Changing attitudes to cardiopulmonary resuscitation in older people: a 15-year
      follow-up study.
AB  - BACKGROUND: while it is well established that individual patient preferences
      regarding cardiopulmonary resuscitation (CPR) may change with time, the stability
      of population preferences, especially during periods of social and economic
      change, has received little attention. OBJECTIVE: to elicit the resuscitation
      preferences of older Irish inpatients and to compare the results with an
      identical study conducted 15 years earlier. METHODS: one hundred and fifty older
      medical inpatients awaiting discharge in a university teaching hospital or a
      district general hospital subjects were asked about resuscitation preferences.
      Results were compared to those elicited from a hundred subjects in 1992. RESULTS:
      most patients (94%) felt it was a good idea for doctors to discuss CPR routinely
      with patients, compared with 39% in 1992. In their current health, 6% in 2007 and
      76% in 1992 would refuse CPR. The independent predictors of refusal of CPR in
      current health on logistic regression were age and year of assessment. In the
      final model, those aged 75-84 years [OR 2.77 (95% CI 1.25-6.13), P = 0.02] and 85
      years or more [OR 15.19 (4.26-54.15), P < 0.0001] were more likely than those
      aged 65-74 years (reference group) to refuse CPR. Those questioned in 2007 [OR
      0.04 (0.02-0.81), P < 0.0001] were less likely than those questioned in 1992
      (reference group) to refuse CPR. CONCLUSIONS: there has been a significant shift
      in the attitudes of older Irish inpatients over 15 years towards favouring
      greater patient participation in decision making and an increased desire for
      resuscitation.

PMID- 19171951
TI  - Improvement in diabetes self-efficacy and glycaemic control using telemedicine in
      a sample of older, ethnically diverse individuals who have diabetes: the IDEATel
      project.
AB  - BACKGROUND: with increasing prevalence of diabetes in older people, it is
      important to understand factors that affect their outcomes. The Informatics for
      Diabetes Education and Telemedicine (IDEATel) project is a demonstration project
      to evaluate the feasibility and effectiveness of telemedicine with diverse,
      medically underserved, older diabetes patients. Subjects were randomised to
      telemedicine case management or usual care. This intervention has been shown to
      result in improved medical outcomes and self-efficacy. Self-efficacy refers to
      one's belief that (s)he can successfully engage in a behaviour. Self-efficacy has
      been shown to relate to behaviour change and glycaemic control in middle-aged
      individuals, but not studied in older individuals. OBJECTIVES: to assess whether
      (a) diabetes self-efficacy relates to the primary medical outcome of glycaemic
      control, and to secondary outcomes (blood pressure and cholesterol), and (b)
      whether, after an intervention, change in diabetes self-efficacy relates to
      change in these medical outcomes in a group of older, ethnically diverse
      individuals. METHODS: three waves of longitudinal data from participants in
      IDEATel were analysed. RESULTS: diabetes self-efficacy at baseline correlated
      with glycaemic control, blood pressure and cholesterol. An increase in diabetes
      self-efficacy over time was related to an improvement in glycaemic control (P <
      0.0001), but not in blood pressure and lipid levels. The intervention was
      significantly related to improved self-efficacy over time (P < 0.0001), and both
      directly (P = 0.022) and indirectly through self-efficacy (P < 0.001) to improved
      glycaemic control. The mediation effect of self-efficacy was also significant (P<
      0.004). CONCLUSIONS: diabetes self-efficacy is a relevant construct for older
      diabetes patients. Thus, interventions that target enhanced self-efficacy may
      also result in improved glycaemic control.

PMID- 19171952
TI  - Pseudomonas arthropathy in an older patient.
AB  - BACKGROUND: septic arthritis caused by Pseudomonas aeruginosa is uncommon in the
      immunocompetent older population, despite its occurrence in younger patients with
      open injuries and in intravenous drug abusers. CASE REPORT: here we report a case
      of septic arthritis caused by P. aeruginosa complicated by death in an older
      patient with recently treated Pseudomonas urinary tract infection. DISCUSSION:
      the diagnosis of Pseudomonas septic arthritis is made on culturing the organism
      from synovial fluid aspirate. Concurrent septic arthritis and crystal arthropathy
      is associated with a high mortality.

PMID- 19171953
TI  - Aerobic potential, stroke parameters, and coordination in swimming front-crawl
      performance.
AB  - The purposes of this review were (1) to review the recent studies conducted in
      swimming on the assessment of aerobic potential and establishment of exercise
      intensity domains (it is important that exercise-intensity domains be accurately
      defined and their physiological underpinnings well understood to optimize and
      evaluate training programs); (2) to analyze changes in traditionally measured
      stroke rate and stroke length during exhaustive swims, particularly in relation
      to the predetermined intensity domains (introduction of an "optimal swimming
      technique speed"); and (3) to introduce the latest swimming research on arm
      coordination that might help us better understand the technical adaptations of
      swimmers under physical stress.

PMID- 19171954
TI  - Physiological responses to exercise on different models of the concept II rowing
      ergometer.
AB  - PURPOSE: The Concept II model C (IIC) rowing ergometer was replaced by the
      Concept II model D (IID), but the design modifications of the updated ergometer
      might alter resistance characteristics and rowing technique, thereby potentially
      influencing ergometer test results. This study evaluated the physiological
      response to rowing on the IIC and IID ergometers during a submaximal progressive
      incremental test and maximal-performance time trial. METHODS: Eight national
      level rowers completed submaximal and maximal tests on the IIC and IID ergometers
      separated by 48 to 72 h. Physiological responses and calculated blood lactate
      thresholds (LT1 and LT2) were compared between ergometer models (IIC vs IID)
      using standardized drag-factor settings. RESULTS: Power output, oxygen
      consumption, rowing economy (mL O2 . min-1 . W-1), heart rate, blood lactate
      concentration, stroke rate, and rating of perceived exertion all displayed
      similar responses regardless of ergometer model. Calculated physiological values
      equivalent to LT1 and LT2 were also similar between models, except for blood
      lactate concentration at LT, which displayed a small but statistically
      significant difference (P = .02) of 0.2 mmol/L. CONCLUSIONS: The physiological
      response when rowing on IIC and IID ergometers is nearly identical, and testing
      can therefore be carried out on either ergometer and the results directly
      compared.

PMID- 19171955
TI  - Highland dance: heart-rate and blood lactate differences between competition and
      class.
AB  - PURPOSE: This study looked at the physiological effects of performance in
      Highland-dance competition to consider whether the traditional methods used
      during class and rehearsal provide an appropriate training stimulus toward this
      performance. METHODS: Nine championship standard, female Highland dancers (age
      14.2 +/- 1.47 years) had their heart rate and blood lactate concentrations
      measured before and after 3 dances during a championship competition. Heart rate
      was also measured during the same 3 dances in rehearsal and during class.
      RESULTS: Repeated-measures analysis of variance showed significant differences in
      predance lactate concentrations between the first dance (Highland Fling, 1.4 +/-
      0.3 mM/L), the second dance (Sword dance, 2.3 +/- 0.8 mM/L), and the third dance
      (Sean Truibhas, 3.5 +/- 1.8 mM/L; F2,16 = 11.72, P < .01. This, coupled with a
      significant rise in lactate concentration during the dances (F1,8 = 76.75, P <
      .001), resulted in a final postdance lactate concentration of 7.3 +/- 2.96 mM/L.
      Heart-rate data during competition, rehearsal, and class (195.0 +/- 6.5, 172.6 +/
      5.4, and 151.9 +/- 7.4 beats/min, respectively) showed significant differences
      between all 3 (F2,16 = 107.1, P < .001); these are comparable to research on
      other dance forms. CONCLUSIONS: Given the disparity between the anaerobic
      predominance of competition and the aerobic predominance during class, it is
      suggested that the class does not provide an appropriate training stimulus as
      preparation for competitive performance in Highland dance.

PMID- 19171956
TI  - The effect of superoxygenated water on blood gases, lactate, and aerobic cycling
      performance.
AB  - CONTEXT: Recently, superoxygenated-water beverages have emerged as a new
      purported ergogenic substance. PURPOSE: This study aimed to determine the effects
      of superoxygenated water on submaximal endurance performance. METHODS: Eleven
      active male subjects, VO2max 52.6 +/- 4.8 mL . kg-1 . min-1, height 180.0 +/- 2.0
      cm, weight 76.0 +/- 7.0 kg, age 24 +/- 1.0 y (mean +/- SD), completed a 45-min
      cycle-ergometry exercise test at 70% of their previously predicted maximal power
      output with a 10-min rest period, followed by a 15-min time trial (TT). Thirty
      min before the exercise test subjects consumed 15 mL of either superoxygenated
      water (E) or placebo (P; water mixed with low-chlorine solution). Subjects then
      completed the test again a week later for the other condition (double-blind,
      randomized). The physiological variables measured during exercise were VO2, VCO2,
      respiratory-exchange ratio (RER), VE, PO2, PCO2, blood lactate (bLa-), and heart
      rate (HR). Mean distance covered and the average power output for the 15-min TT
      were also measured as performance indicators. RESULTS: There were no significant
      differences in VO2, VCO2, RER, VE, bLa-, PO2, and HR (P > .05) during the
      exercise tests. Neither were there any significant improvements in the total
      distance covered (P 9.01 +/- 0.74 km vs E 8.96 +/- 0.68 km, P > .05) or the
      average power output (P 186.7 +/- 35.8 W vs E 179.0 +/- 25.9 W, P > .05) during
      the 15-min TT. CONCLUSION: Based on these results the authors conclude that
      consuming 15 mL of superoxygenated water does not enhance submaximal or maximal
      TT cycling performance.

PMID- 19171957
TI  - A comparison of ballistic-movement and ballistic-intent training on muscle
      strength and activation.
AB  - PURPOSE: Studies have both supported and refuted the concept that it is the
      intent to perform ballistic contractions that determines velocity-specific gains
      in resistance training. The purpose of this investigation was to determine
      whether ballistic intent is as effective as ballistic movement in improving
      muscle activation, force, movement time, and reaction time. METHODS: Subjects
      completed 8 wk of punch training. A dynamic (DYN) group trained with elastic
      resistance bands, and the isometric (ISO) group trained with an unyielding strap.
      A control (CTRL) group was also tested. Pretesting and posttesting measures
      included isometric force; electromyography (EMG) of triceps, biceps, pectoralis
      major, and latissimus dorsi; movement and reaction time of both arms; and a quick
      hands test of coordination. RESULTS: Triceps iEMG increased by 63% in the ISO
      group (P = .03). Pectoralis major iEMG increased by 65% in the DYN group (P =
      .007). Movement time decreased 17.6% in the DYN training group (P = .001).
      Isometric force did not improve in either training group or in the CTRL group.
      CONCLUSIONS: Because of its specificity of movement, dynamic training might be a
      more appropriate method to improve punching speed for martial artists and boxers.
      The intent to contract explosively over a short duration does not appear to be
      beneficial in increasing force production or speed of movement in punching.

PMID- 19171958
TI  - Effect of instability and resistance on unintentional squat-lifting kinetics.
AB  - CONTEXT: Resistance training while using an instability-training device is known
      to increase activation of stabilizing muscle groups while decreasing the force
      generated by the prime movers during isometric contractions. PURPOSE: To
      investigate differences in squat kinetics during dynamic resistance training in
      an increasingly unstable training environment. METHODS: Fourteen active men
      participated in this study. In each testing session, each participant performed 3
      repetitions of squats with a 10-repetition maximum (10-RM) resistance, 40% of
      their 10-RM resistance, and 20.45 kg. The 3 testing session consisted of standing
      on a stable floor, foam pads, or BOSU balls. All repetitions were recorded with
      an optical encoder to record barbell kinetics. RESULTS: The transition from
      stable (floor) to very unstable (BOSU) resulted in high likelihoods (>75%) of
      clinically meaningful differences ranging from small to large (effect size [ES]
      0.31-1.73) in factors relating to concentric kinetics, eccentric power, and squat
      depth, regardless of the resistance used for training. There were also likely
      differences at the heaviest resistance in peak concentric power (stable to foam:
      ES 2.06; foam to BOSU: ES 0.38), eccentric power (stable to foam: ES 1.88; foam
      to BOSU: ES 0.74), and squat depth (stable to foam: ES 0.50; foam to BOSU: ES
      0.67). CONCLUSIONS: Resistance training in an unstable environment at an
      intensity sufficient to elicit strength gains of the prime movers results in
      deleterious effects in concentric squat kinetics and squat technique. Such
      observations are particularly evident on very unstable platforms.

PMID- 19171959
TI  - Relationship between throwing velocity, muscle power, and bar velocity during
      bench press in elite handball players.
AB  - PURPOSE: The purpose of this study was to examine the relationship between ball
      throwing velocity during a 3-step running throw and dynamic strength, power, and
      bar velocity during a concentric-only bench-press exercise in team-handball
      players. METHODS: Fourteen elite senior male team-handball players volunteered to
      participate. Each volunteer had power and bar velocity measured during a
      concentric-only bench-press test with 26, 36, and 46 kg, as well as having 1
      repetition-maximum (1-RMBP) strength determined. Ball-throwing velocity was
      evaluated with a standard 3-step running throw using a radar gun. RESULTS: Ball
      throwing velocity was related to the absolute load lifted during the 1-RMBP (r =
      .637, P = .014), peak power using 36 kg (r = .586, P = .028) and 46 kg (r = .582,
      P = .029), and peak bar velocity using 26 kg (r = .563, P = .036) and 36 kg (r =
      .625, P = .017). CONCLUSIONS: The results indicate that throwing velocity of
      elite team-handball players is related to maximal dynamic strength, peak power,
      and peak bar velocity. Thus, a training regimen designed to improve ball-throwing
      velocity in elite male team-handball players should include exercises that are
      aimed at increasing both strength and power in the upper body.

PMID- 19171960
TI  - Caffeine, carbohydrate, and cooling use during prolonged simulated tennis.
AB  - PURPOSE: To determine the effects of prolonged simulated tennis on performance
      and the ergogenic potential of caffeine, carbohydrates, and cooling. METHODS:
      Twelve highly trained male tennis players (age 18.3 +/- 3.0 y, height 178.8 +/-
      8.5 cm, body mass 73.95 +/- 12.30 kg, mean +/- SD) performed 4 simulated matches
      (2 h 40 min) against a ball machine on an indoor hard court. The counterbalanced
      experimental trials involved caffeine supplementation (3 mg/kg), carbohydrate
      supplementation (6% solution), precooling and intermittent cooling, and placebo
      control. Physiological markers (core temperature, heart rate, blood lactate, and
      blood glucose), subjective responses (ratings of perceived exertion and thermal
      sensation), stroke velocity and accuracy, serve kinematics, and tennis-specific
      perceptual skill quantified the efficacy of interventions. RESULTS: Significant
      effects of time (P < .01) reflected increased physiological demand, reduced serve
      velocity and ground-stroke velocity and accuracy, and a slowing of the serve
      racket-arm acceleration phase. Caffeine increased serve velocity (165 +/- 15
      km/h) in the final set of the match (P = .014) compared with placebo (159 +/- 15
      km/h, P = .008) and carbohydrate (158 +/- 13 km/h, P = .001) conditions.
      Carbohydrate and cooling conditions afforded physiological advantage (increased
      blood glucose, P < .01, and reduced preexercise thermal sensation, P < .01) but
      did not affect performance relative to the placebo condition. CONCLUSIONS:
      Prolonged simulated tennis induced significant decrements in tennis skills.
      Caffeine supplementation partly attenuated the effects of fatigue and increased
      serve velocity. In contrast, carbohydrate and cooling strategies had little
      ergogenic effect on tennis performance.

PMID- 19171961
TI  - The application of postactivation potentiation to elite sport.
AB  - Recently there has been considerable interest and research into the functional
      significance of postactivation potentiation (PAP) on sport performance. The
      interest has evolved around the potential for enhancing acute performance or the
      long-term training effect, typically in the form of complex training. Complex
      training usually involves performing a weight-training exercise with high loads
      before executing a plyometric exercise with similar biomechanical demands.
      Despite a considerable amount of research in the past 10 years it would seem
      there is still much research to be done to fully determine whether PAP has a
      functional role and, if so, how to best exploit it. It is clear from the research
      that there are many factors that need to be considered when attempting to apply
      PAP to an athlete. It is possible that a well-conceived sport-specific warm-up
      might be as or more effective in enhancing acute performance and easier to apply
      in a practical setting. In addition, despite its current popularity, there has
      not been 1 study that has effectively examined the efficacy of complex training
      and whether it has any advantage over other forms of training that combine weight
      training and plyometrics but not in the same training session.

PMID- 19171962
TI  - Measurement agreement (repeatability) for a countermovement jump protocol using a
      portable forceplate.
AB  - This study assessed measurement agreement of jump-height measures derived from a
      portable forceplate sampling at 500 Hz. Female (n = 42) and male (n = 30)
      participants (total N = 72, age = 19.7 +/- 2.8 y, height = 174.5 +/- 9.3 cm, mass
      = 71.4 +/- 12.8 kg) performed 25 separate maximal jump attempts. This
      incorporated 5 sets of 5 single jumps. One min of rest was allowed between jump
      attempts, with a 3-min rest period between sets. For each participant, the best
      jump height for each set of 5 jumps was kept for analysis. No systematic bias was
      identified, and the best jump height was stable within participants across all 5
      sets of jumps. Therefore, factors such as fatigue and learning did not affect the
      measures. Females did jump lower (P = or < .0001) than their male counterparts,
      justifying additional analysis of agreement for the 2 gender groups.
      Heteroscedasticity was found, so ratio limits of agreement (LOAs) were calculated
      by using the antilog of the log-transformed data. The calculated ratio LOAs were
      x// 1.08 for the total group, x// 1.08 for females, and x// 1.08 for males. From
      the calculated ratio LOA, the jump protocol was shown to provide stable measures
      of jump height. In addition, the ratio LOA can be helpful to interpret findings
      from research that report jump height derived from the same protocol and
      assessing participants from the studied population (ie, active university-age
      male, female, or combined-gender groups).

PMID- 19171963
TI  - Modeling the temporal evolution of the Drosophila gene expression from DNA
      microarray time series.
AB  - The time evolution of gene expression across the developmental stages of the host
      organism can be inferred from appropriate DNA microarray time series. Modeling
      this evolution aims eventually at improving the understanding and prediction of
      the complex phenomena that are the basis of life. We focus on the embryonic-to
      adult development phases of Drosophila melanogaster, and chose to model the
      expression network with the help of a system of differential equations with
      constant coefficients, which are nonlinear in the transcript concentrations but
      linear in their logarithms. To reduce the dimensionality of the problem, genes
      having similar expression profiles are grouped into 17 clusters. We show that a
      simple linear model is able to reproduce the experimental data with very good
      precision, owing to the large number of parameters that represent the connections
      between the clusters. Remarkably, the parameter reduction allowed elimination of
      up to 80-85% of these connections while keeping fairly good precision. This
      result supports the low-connectivity hypothesis of gene expression networks, with
      about three connections per cluster, without introducing a priori hypotheses. The
      core of the network shows a few gene clusters with negative self-regulation, and
      some highly connected clusters involving proteins with crucial functions.

PMID- 19171964
TI  - Imperfect pseudo-merohedral twinning in crystals of fungal fatty acid synthase.
AB  - The recent high-resolution structures of fungal fatty acid synthase (FAS) have
      provided new insights into the principles of fatty acid biosynthesis by large
      multifunctional enzymes. The crystallographic phase problem for the 2.6 MDa
      fungal FAS was initially solved to 5 A resolution using two crystal forms from
      Thermomyces lanuginosus. Monoclinic crystals in space group P2(1) were obtained
      from orthorhombic crystals in space group P2(1)2(1)2(1) by dehydration. Here, it
      is shown how this space-group transition induced imperfect pseudo-merohedral
      twinning in the monoclinic crystal, giving rise to a Moire pattern-like
      interference of the two twin-related reciprocal lattices. The strategy for
      processing the twinned diffraction images and obtaining a quantitative analysis
      is presented. The twinning is also related to the packing of the molecules in the
      two crystal forms, which was derived from self-rotation function analysis and
      molecular-replacement solutions using a low-resolution electron microscopy map as
      a search model.

PMID- 19171965
TI  - Structure-function studies of the RNA polymerase II elongation complex.
AB  - RNA polymerase II (Pol II) is the eukaryotic enzyme that is responsible for
      transcribing all protein-coding genes into messenger RNA (mRNA). The mRNA
      transcription cycle can be divided into three stages: initiation, elongation and
      termination. During elongation, Pol II moves along a DNA template and synthesizes
      a complementary RNA chain in a processive manner. X-ray structural analysis has
      proved to be a potent tool for elucidating the mechanism of Pol II elongation.
      Crystallographic snapshots of different functional states of the Pol II
      elongation complex (EC) have elucidated mechanistic details of nucleotide
      addition and Pol II translocation. Further structural studies in combination with
      in vitro transcription experiments led to a mechanistic understanding of various
      additional features of the EC, including its inhibition by the fungal toxin alpha
      amanitin, the tunability of the active site by the elongation factor TFIIS, the
      recognition of DNA lesions and the use of RNA as a template.

PMID- 19171966
TI  - Model-building strategies for low-resolution X-ray crystallographic data.
AB  - The interpretation of low-resolution X-ray crystallographic data proves to be
      challenging even for the most experienced crystallographer. Ambiguity in the
      electron-density map makes main-chain tracing and side-chain assignment
      difficult. However, the number of structures solved at resolutions poorer than
      3.5 A is growing rapidly and the structures are often of high biological interest
      and importance. Here, the challenges faced in electron-density interpretation,
      the strategies that have been employed to overcome them and developments to
      automate the process are reviewed. The methods employed in model generation from
      electron microscopy, which share many of the same challenges in providing high
      confidence models of macromolecular structures and assemblies, are also
      considered.

PMID- 19171967
TI  - X-ray structure determination at low resolution.
AB  - As an example of structure determination in the 3.5-4.5 A resolution range,
      crystal structures of the ATPase p97/VCP, consisting of an N-terminal domain
      followed by a tandem pair of ATPase domains (D1 and D2), are discussed. The
      structures were originally solved by molecular replacement with the high
      resolution structure of the N-D1 fragment of p97/VCP, whereas the D2 domain was
      manually built using its homology to the D1 domain as a guide. The structure of
      the D2 domain alone was subsequently solved at 3 A resolution. The refined model
      of D2 and the high-resolution structure of the N-D1 fragment were then used as
      starting models for re-refinement against the low-resolution diffraction data for
      full-length p97. The re-refined full-length models showed significant improvement
      in both secondary structure and R values. The free R values dropped by as much as
      5% compared with the original structure refinements, indicating that refinement
      is meaningful at low resolution and that there is information in the diffraction
      data even at approximately 4 A resolution that objectively assesses the quality
      of the model. It is concluded that de novo model building is problematic at low
      resolution and refinement should start from high-resolution crystal structures
      whenever possible.

PMID- 19171968
TI  - On vital aid: the why, what and how of validation.
AB  - Limitations to the data and subjectivity in the structure-determination process
      may cause errors in macromolecular crystal structures. Appropriate validation
      techniques may be used to reveal problems in structures, ideally before they are
      analysed, published or deposited. Additionally, such techniques may be used a
      posteriori to assess the (relative) merits of a model by potential users. Weak
      validation methods and statistics assess how well a model reproduces the
      information that was used in its construction (i.e. experimental data and prior
      knowledge). Strong methods and statistics, on the other hand, test how well a
      model predicts data or information that were not used in the structure
      determination process. These may be data that were excluded from the process on
      purpose, general knowledge about macromolecular structure, information about the
      biological role and biochemical activity of the molecule under study or its
      mutants or complexes and predictions that are based on the model and that can be
      tested experimentally.

PMID- 19171969
TI  - Case-controlled structure validation.
AB  - Although many factors influence the quality of a macromolecular crystal
      structure, validation criteria are usually only calibrated using one of these
      factors, the resolution. For many purposes this is sufficient, but there are
      times when one wishes to compare one set of structures with another and the
      comparison may be invalidated by systematic differences between the sets in
      factors other than resolution. This problem can be circumvented by borrowing from
      medicine the idea of the case-matched control: each structure of interest is
      matched with a control structure that has similar values for all relevant factors
      considered in this study. In addition to resolution, these include the size of
      the structure (as measured by the volume of the asymmetric unit) and the year of
      deposition. This approach has been applied to address two questions: whether
      structures from structural genomics efforts reach the same level of quality as
      structures from traditional sources and whether the impact factor of the journal
      in which a structure is published correlates with structure quality. In both
      cases, once factors influencing quality have been controlled in the comparison,
      there is little evidence for a systematic difference in quality.

PMID- 19171970
TI  - Structure validation in chemical crystallography.
AB  - Automated structure validation was introduced in chemical crystallography about
      12 years ago as a tool to assist practitioners with the exponential growth in
      crystal structure analyses. Validation has since evolved into an easy-to-use
      checkCIF/PLATON web-based IUCr service. The result of a crystal structure
      determination has to be supplied as a CIF-formatted computer-readable file. The
      checking software tests the data in the CIF for completeness, quality and
      consistency. In addition, the reported structure is checked for incomplete
      analysis, errors in the analysis and relevant issues to be verified. A validation
      report is generated in the form of a list of ALERTS on the issues to be
      corrected, checked or commented on. Structure validation has largely eliminated
      obvious problems with structure reports published in IUCr journals, such as
      refinement in a space group of too low symmetry. This paper reports on the
      current status of structure validation and possible future extensions.

PMID- 19171972
TI  - Prospects for de novo phasing with de novo protein models.
AB  - The prospect of phasing diffraction data sets ;de novo' for proteins with
      previously unseen folds is appealing but largely untested. In a first systematic
      exploration of phasing with Rosetta de novo models, it is shown that all-atom
      refinement of coarse-grained models significantly improves both the model quality
      and performance in molecular replacement with the Phaser software. 15 new cases
      of diffraction data sets that are unambiguously phased with de novo models are
      presented. These diffraction data sets represent nine space groups and span a
      large range of solvent contents (33-79%) and asymmetric unit copy numbers (1-4).
      No correlation is observed between the ease of phasing and the solvent content or
      asymmetric unit copy number. Instead, a weak correlation is found with the length
      of the modeled protein: larger proteins required somewhat less accurate models to
      give successful molecular replacement. Overall, the results of this survey
      suggest that de novo models can phase diffraction data for approximately one
      sixth of proteins with sizes of 100 residues or less. However, for many of these
      cases, ;de novo phasing with de novo models' requires significant investment of
      computational power, much greater than 10(3) CPU days per target. Improvements in
      conformational search methods will be necessary if molecular replacement with de
      novo models is to become a practical tool for targets without homology to
      previously solved protein structures.

PMID- 19171971
TI  - Analysis and validation of carbohydrate three-dimensional structures.
AB  - Knowledge of the three-dimensional structures of the carbohydrate molecules is
      indispensable for a full understanding of the molecular processes in which
      carbohydrates are involved, such as protein glycosylation or protein-carbohydrate
      interactions. The Protein Data Bank (PDB) is a valuable resource for three
      dimensional structural information on glycoproteins and protein-carbohydrate
      complexes. Unfortunately, many carbohydrate moieties in the PDB contain
      inconsistencies or errors. This article gives an overview of the information that
      can be obtained from individual PDB entries and from statistical analyses of sets
      of three-dimensional structures, of typical problems that arise during the
      analysis of carbohydrate three-dimensional structures and of the validation tools
      that are currently available to scientists to evaluate the quality of these
      structures.

PMID- 19171973
TI  - Re-refinement from deposited X-ray data can deliver improved models for most PDB
      entries.
AB  - The deposition of X-ray data along with the customary structural models defining
      PDB entries makes it possible to apply large-scale re-refinement protocols to
      these entries, thus giving users the benefit of improvements in X-ray methods
      that have occurred since the structure was deposited. Automated gradient
      refinement is an effective method to achieve this goal, but real-space
      intervention is most often required in order to adequately address problems
      detected by structure-validation software. In order to improve the existing
      protocol, automated re-refinement was combined with structure validation and
      difference-density peak analysis to produce a catalogue of problems in PDB
      entries that are amenable to automatic correction. It is shown that re-refinement
      can be effective in producing improvements, which are often associated with the
      systematic use of the TLS parameterization of B factors, even for relatively new
      and high-resolution PDB entries, while the accompanying manual or semi-manual map
      analysis and fitting steps show good prospects for eventual automation. It is
      proposed that the potential for simultaneous improvements in methods and in re
      refinement results be further encouraged by broadening the scope of depositions
      to include refinement metadata and ultimately primary rather than reduced X-ray
      data.

PMID- 19171975
TI  - Analysis of errors in the structure determination of MsbA.
AB  - The determination of incorrect structures for the ABC transporter MsbA gave rise
      to questions of how this could have occurred. Methodological aspects of the MsbA
      structure determination are explored in light of this error.

PMID- 19171974
TI  - An emerging consensus for the structure of EmrE.
AB  - The archetypical member of the small multidrug-resistance family is EmrE, a
      multidrug transporter that extrudes toxic polyaromatic cations from the cell
      coupled to the inward movement of protons down a concentration gradient. The
      architecture of EmrE was first defined from the analysis of two-dimensional
      crystals by cryoelectron microscopy (cryo-EM), which showed that EmrE was an
      unusual asymmetric dimer formed from a bundle of eight alpha-helices. The most
      favoured interpretation of the structure was that the monomers were oriented in
      opposite orientations in the membrane in an antiparallel orientation. A model was
      subsequently built based upon the cryo-EM data and evolutionary constraints and
      this model was consistent with mutagenic data indicating which amino-acid
      residues were important for substrate binding and transport. Two X-ray structures
      that differed significantly from the cryo-EM structure were subsequently
      retracted owing to a data-analysis error. However, the revised X-ray structure
      with substrate bound is extremely similar to the model built from the cryo-EM
      structure (r.m.s.d. of 1.4 A), suggesting that the proposed antiparallel
      orientation of the monomers is indeed correct; this represents a new structural
      paradigm in membrane-protein structures. The vast majority of mutagenic and
      biochemical data corroborate this structure, although cross-linking studies and
      recent EPR data apparently support a model of EmrE that contains parallel dimers.

PMID- 19171976
TI  - Non-compliance in dermatologic diseases.

PMID- 19171977
TI  - From the desk of the guest editor. Seminar: chronic arsenicosis in India.

PMID- 19171978
TI  - Pathogenesis, clinical features and pathology of chronic arsenicosis.
AB  - Arsenicosis is a multisystem disorder, with virtually no system spared from its
      vicious claw; though its predominant manifestations are linked to cutaneous
      involvement. Cutaneous effects take the form of pigmentary changes,
      hyperkeratosis, and skin cancers (Bowen's disease, squamous cell carcinoma, and
      basal cell epithelioma). Peripheral vascular disease (blackfoot disease),
      hypertension, ischemic heart disease, noncirrhotic portal hypertension,
      hepatomegaly, peripheral neuropathy, respiratory and renal involvement, bad
      obstetrical outcome, hematological disturbances, and diabetes mellitus are among
      the other clinical features linked to arsenic toxicity. The effects are mediated
      principally by the trivalent form of arsenic (arsenite), which by its ability to
      bind with sulfhydryl groups present in various essential compounds leads to
      inactivation and derangement of body function. Though the toxicities are mostly
      linked to the trivalent state, arsenic is consumed mainly in its pentavalent form
      (arsenate), and reduction of arsenate to arsenite is mediated through
      glutathione. Body attempts to detoxify the agent via repeated oxidative
      methylation and reduction reaction, leading to the generation of methylated
      metabolites, which are excreted in the urine. Understandably the
      detoxification/bio-inactivation process is not a complete defense against the
      vicious metalloid, and it can cause chromosomal aberration, impairment of DNA
      repair process, alteration in the activity of tumor suppressor gene, etc.,
      leading to genotoxicity and carcinogenicity. Arsenic causes apoptosis via free
      radical generation, and the cutaneous toxicity is linked to its effect on various
      cytokines (e.g., IL-8, TGF-beta, TNF-alpha, GM-CSF), growth factors, and
      transcription factors. Increased expression of cytokeratins, keratin-16 (marker
      for hyperproliferation) and keratin-8 and -18 (marker for less differentiated
      epithelial cells), can be related to the histopathological findings of
      hyperkeratosis and dysplastic cells in the arsenicosis skin lesion.

PMID- 19171979
TI  - Arsenicosis: diagnosis and treatment.
AB  - Diagnosis of arsenicosis relies on both clinical and laboratory criteria, but
      principally it can be diagnosed on the basis of its cutaneous manifestations.
      Cutaneous manifestations (melanosis, keratosis, and cutaneous cancers) are
      essential clues in the diagnosis, and trained dermatologists or arsenic experts
      are able to clinically confirm a case even without laboratory backup. Although
      systemic manifestations are not considered as diagnostic hallmarks, yet their
      presence serves as important telltale signs in arriving at the diagnosis. In
      countries where laboratory facilities are available, measuring the level of
      arsenic in drinking water (consumed in the last 6 months), urine, hair, and nails
      is of immense value. Newer biomarkers of arsenic exposure are being explored to
      provide early information about arsenic intoxication, of which urinary porphyrin
      level, blood metallothionein have shown promising results. Controlling the
      problem of arsenicosis depends on various factors, of which the most important is
      cessation of intake of arsenic-contaminated water. Deep wells, traditional dug
      wells, treatment of surface water, rainwater harvesting, and removing arsenic
      from the contaminated water by arsenic removal plant or arsenic treatment unit
      are the available options for providing arsenic-free drinking water. The role of
      nutrition and antioxidants in preventing the onset of symptoms of arsenicosis is
      also of importance. Nonspecific therapies (e.g., keratolytics for hyperkeratosis)
      cannot also be ignored and serve as palliative measures. The persons affected
      need to be followed up at regular intervals to detect the onset of cancers (if
      any) at the earliest. Role of counseling and education should never be
      underestimated since absence of public awareness can undermine all efforts of
      mitigation measures.

PMID- 19171980
TI  - Epidemiology and prevention of chronic arsenicosis: an Indian perspective.
AB  - Arsenicosis is a global problem but the recent data reveals that Asian countries,
      India and Bangladesh in particular, are the worst sufferers. In India, the state
      of West Bengal bears the major brunt of the problem, with almost 12 districts
      presently in the grip of this deadly disease. Recent reports suggest that other
      states in the Ganga/Brahmaputra plains are also showing alarming levels of
      arsenic in ground water. In West Bengal, the majority of registered cases are
      from the district of Nadia, and the maximum number of deaths due to arsenicosis
      is from the district of South 24 Paraganas. The reason behind the problem in
      India is thought to be mainly geogenic, though there are instances of reported
      anthropogenic contamination of arsenic from industrial sources. The reason for
      leaching of arsenic in ground water is attributed to various factors, including
      excessive withdrawal of ground water for the purpose of irrigation, use of bio
      control agents and phosphate fertilizers. It remains a mystery why all those who
      are exposed to arsenic-contaminated water do not develop the full-blown disease.
      Various host factors, such as nutritional status, socioeconomic status, and
      genetic polymorphism, are thought to make a person vulnerable to the disease. The
      approach to arsenicosis mitigation needs be holistic, sustainable, and
      multidisciplinary, with the 2 main pillars being health education and provision
      of 'arsenic-free water.' In the state of West Bengal, the drive for arsenic
      mitigation has been divided into 3 phases using various methods, including new
      hand pumps/tube wells at alternative deep aquifers, dug wells, arsenic removal
      plants, arsenic treatment units, as well as piped and surface water supply
      schemes. The methods have their own limitations, so it is intended that a
      pragmatic approach be followed in the arsenicosis prevention drive. It is also
      intended that the preventive measures be operationally and economically feasible
      for the people living in the affected areas.

PMID- 19171981
TI  - Role of stressful life events in induction or exacerbation of psoriasis and
      chronic urticaria.
AB  - BACKGROUND: The possibility of a causal influence of emotional stress, especially
      of stressful life events, on the course of various skin diseases has long been
      postulated. Previous reports addressing its influence on skin psoriasis and
      chronic urticaria have been mainly anecdotal. OBJECTIVE: The aim of this study
      was to evaluate the stressful events of life within 1 year preceding onset or
      exacerbation of skin disease in patients of psoriasis vulgaris and chronic
      urticaria. METHOD: Fifty consecutive clinically diagnosed psoriasis patients and
      50 consecutive clinically diagnosed chronic urticaria patients were examined
      clinically and administered Gurmeet Singh's presumptive stressful life events
      scale. RESULTS: Stressful life events were seen in 26% of the patients in the
      psoriasis vulgaris group and 16% of the patients in the chronic urticaria group
      within 1 year preceding onset or exacerbation of skin disease. In the psoriasis
      vulgaris group, the most common stressful life event seen was financial loss or
      problems (8%), followed by death of close family member (4%), sexual problems
      (4%), family conflict (2%), major personal illness or injury (2%), and transfer
      or change in working conditions (2%), failure in examinations (2%), family member
      unemployed (2%), illness of family member (2%), getting married or engaged (2%),
      miscellaneous (2%). In the chronic urticaria group, the most common stressful
      life event seen was death of a close family member (6%), followed by family
      conflict (2%), financial loss or problems (2%), sexual problems (2%), illness of
      family member (2%), getting married or engaged (2%), trouble at work with
      colleagues, superiors, or subordinates (2%), going on a pleasure trip (2%) and
      extramarital relations (2%). CONCLUSION: Psychological stress plays a significant
      role in triggering or exacerbating dermatological diseases. Our study indicates
      the role of relaxation therapies and stress management programs in chronic
      diseases such as psoriasis and chronic urticaria. Psychological interventions can
      help individuals to reinterpret events and develop strategies to cope with
      stressful events, thus decreasing morbidity due to these diseases.

PMID- 19171982
TI  - Quality of life in psoriasis: a study from south India.
AB  - BACKGROUND: Psoriasis can have a profound impact on a patient's quality of life.
      Very few Indian studies have examined this aspect of Indian patients of
      psoriasis. AIMS: This study was conducted to assess the clinical severity, as
      well as physical and psychosocial disability, and stress incurred and to analyze
      their interrelationship in psoriasis patients aged more than 18 years. METHODS:
      This hospital-based cross-sectional study was conducted in the Department of
      Dermatology, JIPMER, Pondicherry, India. Clinical severity, physical and
      psychosocial morbidity, and the stress incurred were measured using psoriasis
      area severity index (PASI), psoriasis disability index (PDI), and psoriasis life
      stress inventory (PLSI) respectively, the latter two of which were suitably
      modified and translated into the local language, viz., Tamil. Appropriate tests
      were conducted using SPSS for Windows (Release 7.5.1) statistical software.
      RESULTS: Fifty patients (34 males, 16 females) were included in the study. The
      clinical PASI scores correlated significantly with the overall physical
      disability (PDI), individual aspects of the PDI (except the treatment-related
      activities), and the measurement of stress incurred (PLSI). A PASI score of more
      than 18 delineated a subgroup of patients with higher overall physical disability
      and higher stress rating. Among the physical and psychosocial factors
      investigated, daily activities, employment, and treatment were reported to be
      affected the most. Psoriasis sufferers are also most likely to feel self
      conscious, be disturbed / inconvenienced by the shedding of the skin, live in a
      constant fear of relapse, and avoid social interactions. CONCLUSIONS: The present
      study provides compelling evidence that psoriasis affects the quality of life,
      and it highlights the importance of adopting a multidimensional assessment of
      psoriasis.

PMID- 19171983
TI  - Cutaneous manifestations in 404 Iranian patients with inflammatory bowel disease:
      a retrospective study.
AB  - BACKGROUND: Cutaneous manifestations of inflammatory bowel disease are relatively
      common, although they vary widely. AIMS: The aim of this study was to determine
      the prevalence of cutaneous manifestations in inflammatory bowel disease
      according to their location, age, gender, activity, and type of underlying
      disease in an Iranian population during a 10-year period. METHODS: The medical
      records of 404 inpatients with inflammatory bowel disease were extracted
      retrospectively to detect cutaneous manifestations. RESULTS: In this study, the
      prevalence of cutaneous manifestations was 5.9%. These manifestations were higher
      in Crohn's disease (7.29%) than in ulcerative colitis (4.07%), and more frequent
      in females (52%) than in males (48%). Aphthous stomatitis was observed more
      frequently in Crohn's disease; however, pyoderma gangrenosum was seen more often
      in ulcerative colitis. Erythema nodosum was diagnosed only in female patients
      with Crohn's disease. Manifestations secondary to nutritional deficiency or
      associated conditions including psoriasis and other autoimmune disorders were
      less frequent. CONCLUSIONS: Aphthous stomatitis, pyoderma gangrenosum, and
      erythema nodosum were the most common skin disorders related to inflammatory
      bowel disease (IBD), which mainly occurred in women.

PMID- 19171984
TI  - An uncontrolled, open label study of sulfasalazine in severe alopecia areata.
AB  - BACKGROUND: Alopecia areata (AA) is an autoimmune disease mediated by T
      lymphocytes. Many treatments have been used but their results remain
      disappointing. There is a need to propose new therapeutic alternatives. METHODS:
      During a period of 3 years, 26 patients with recalcitrant or severe AA (>40% hair
      loss) were enrolled in an open-label uncontrolled clinical trial. According to
      the response to sulfasalazine, patients were grouped into 3 categories: no hair
      regrowth (< 10% terminal hair), partial hair regrowth (10%-90% terminal hair),
      and complete hair regrowth (90%-100% terminal hair). Efficacy evaluation was
      performed with clinical examination. RESULTS: Twenty-two patients completed the
      treatment. Overall, 68.2% (15 of 22 patients) responded to therapy: 27.3% (6 of
      22 patients) achieved complete hair regrowth, and 40.9% had partial hair
      regrowth. Seven (31.8%) patients had no hair regrowth. Of the 22 patients with
      complete and partial remission, 10 (45.5%) suffered a partial or complete
      relapse. Side effects following treatment were seen in 7 (31.8%) patients.
      CONCLUSION: Sulfasalazine could be considered as a therapeutic alternative in the
      treatment of AA, because of its safety profile, cosmetically acceptable efficacy,
      and good tolerability.

PMID- 19171985
TI  - An open, nonrandomized, comparative study of imiquimod 5% cream versus 10%
      potassium hydroxide solution in the treatment of molluscum contagiosum.
AB  - BACKGROUND: There are numerous therapeutic modalities available for treatment of
      molluscum contagiosum. However, the ablative modalities are painful and not
      suitable for children. AIM: We aimed to evaluate and compare the safety and
      efficacy of 2 of the painless modalities, viz., 5% imiquimod cream and 10%
      potassium hydroxide (KOH) solution, in the treatment of molluscum contagiosum.
      METHODS: Out of a total of 40 patients of molluscum contagiosum in the study, 18
      patients in the imiquimod group and 19 patients in the KOH group completed the
      study. The given medication was applied by the patient or a parent to mollusca at
      night, 3 days per week. Imiquimod was continued till clinical cure; and 10% KOH,
      till lesions showed signs of inflammation. Assessments of response and side
      effects were performed at the end of week 4, week 8, and week 12. Significance
      was tested by Student's t test and Mann-Whitney test. RESULTS: The mean lesion
      count decreased from 22.39 to 10.75 with imiquimod and from 20.79 to 4.31 with
      KOH at the end of 12 weeks. We found complete clearance of lesions in 8 (44%)
      patients with imiquimod and in 8 (42.1%) patients with 10% KOH. Minor side
      effects were seen in 15 (78.9%) patients on KOH and 10 (55.5%) patients on
      imiquimod. CONCLUSIONS: The results of this study suggest that both 5% imiquimod
      cream and 10% KOH solution are equally effective in molluscum contagiosum though
      KOH has a faster onset of action. However, KOH solution is associated with a
      higher incidence of side effects.

PMID- 19171986
TI  - Immune reconstitution inflammatory syndrome.
AB  - BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical
      deterioration in clinical status in a patient on antiretroviral treatment (ART)
      despite satisfactory control of viral replication and improvement of CD4 count.
      AIM: To study development of IRIS as a part of ART. METHODS: Hundred patients on
      antiretroviral treatment were studied prospectively in the Department of Skin and
      VD over a period of 2 years. Patients were asked to come if they developed any
      symptoms or on a monthly basis. They were screened clinically and investigated
      suitably for evidence of opportunistic infections. RESULTS: Out of 100 patients,
      10 patients did not come for follow-up. Twenty (22.2%) out of the 90 patients
      developed IRIS. Herpes zoster (HZ), herpes simplex virus (HSV), and tuberculosis
      (TB) were the cases of IRIS seen in the present study. CONCLUSIONS: IRIS in terms
      of HSV/TB is known to accelerate HIV disease progression. Hence early detection
      and prompt treatment, along with continuation of highly active ART, are of utmost
      importance.

PMID- 19171987
TI  - Keratinocyte-melanocyte graft technique followed by PUVA therapy for stable
      vitiligo.
AB  - BACKGROUND: Various surgical procedures for correcting stable vitiligo exist but
      these have their own limitations. Autologous, non-cultured, non-trypsinized,
      melanocyte plus keratinocyte grafting is a new and simple method of vitiligo
      surgery. OBJECTIVE: The study aimed to evaluate efficacy of a new grafting
      technique in vitiligo patches. METHODS: Eighteen vitiligo patches underwent this
      procedure. The upper layer of epidermis was removed by superficial dermabrasion
      using a dermabrader micromotor until the epidermis appeared wet and shiny. Then,
      antibiotic ointment was applied and dermabrasion was continued up to the whitish
      area of the upper dermis. The paste-like material (ointment with entangled
      epidermal particles) was collected and spread over the dermabraded recipient
      site. RESULTS: Pigmentation usually started at 4-6 weeks. Complete uniform
      pigmentation took 16-20 weeks. CONCLUSION: For smaller vitiligo patches this
      method gives cosmetically acceptable results. It is easy to perform and does not
      require specific laboratory setup.

PMID- 19171988
TI  - Clinicopathologic analysis of 21 cases of nevus sebaceus: a retrospective study.
AB  - BACKGROUND: Nevus sebaceus (NS), otherwise designated as 'organoid nevus',
      involves proliferative changes of the sebaceous glands, sweat glands, and the
      hair follicles. It displays a range of appearances, depending on the lesion's
      age. AIMS: To study the histopathological features of NS and correlate these with
      clinical findings. METHODS: All skin biopsy specimens over a 12-year period from
      1995 to 2007 which had a diagnosis of NS were included. Clinical data with follow
      up notes and histopathology were reviewed. RESULTS: Half of the cases had a
      verrucous clinical appearance, while the rest presented as papules, plaques, or
      patches. All the cases showed immature hair follicles, and 24% of cases showed
      immature sebaceous glands. Normal terminal hair follicles were characteristically
      absent in the lesion. Nineteen percent of the cases showed dilated apocrine
      glands, and 14% showed hyperplasia of eccrine glands. Epidermal changes in the
      form of acanthosis, papillomatosis, and hyperkeratosis were seen in 86% of cases.
      Dilated keratin-filled infundibula were observed in 24% of cases. One case was
      associated with a squamous cell carcinoma. CONCLUSIONS: Nevus sebaceus is a
      cutaneous hamartoma, consisting of various elements indigenous to the organ.
      Normal terminal hair follicles are characteristically absent in the lesion
      although the same may be seen in rest of the epidermis, a feature of diagnostic
      importance, not usually highlighted in literature. The divergent differentiation
      observed in NS is consistent with the common embryologic origin of the
      folliculosebaceous-apocrine unit and should not mislead the pathologist.

PMID- 19171990
TI  - Brooke-Spiegler syndrome.
AB  - The Brooke-Spiegler syndrome (BSS) is an uncommon autosomal dominant disorder
      characterized by a high affinity to form multiple adnexal neoplasia (skin
      appendage tumors), especially trichoepitheliomas and cylindromas, and
      occasionally spiradenomas, which usually appear in the second or third decade of
      life. To date, only a few cases with this syndrome have been reported. This case
      report describes a 26-year-old woman who presented to the dermatology department
      of Qaem Hospital with tumoral lesions on her scalp, face, and forearm. Her father
      and younger brother were also affected. On examination, several round-to-oval
      skin-colored papules with a smooth pearly surface measuring 2 to 6 mm in diameter
      were seen on the mid-face, particularly in the nasolabial folds, the upper lip.
      Tumors and nodules seen on the scalp were pinkish red, dome-shaped, and to some
      extent, pedunculated with surface telangiectasia and induration. Histopathology
      of the facial papules showed trichoepithelioma while that of a scalp nodule
      showed cylindroma.

PMID- 19171989
TI  - Topical immunotherapy with diphenylcyclopropenone in vitiligo: a preliminary
      experience.
AB  - BACKGROUND: Despite recent significant therapeutic advances, vitiligo remains a
      clinical conundrum. Topical immunotherapy has been extensively tested in the
      treatment of various dermatologic disorders, especially those believed to have an
      immunologic basis. AIM: To evaluate the role of topical diphenylcyclopropenone
      (DPCP) in the treatment of vitiligo. METHODS: Nineteen patients with limited
      vitiligo lesions were enrolled in this study. After sensitization with 2% lotion
      of DPCP in acetone, progressively higher concentrations beginning at 0.001% up to
      2% were applied weekly for 6 months to the depigmented skin lesions. RESULTS:
      Thirteen of the 19 patients were evaluated at the end of 6 months. Four patients
      with focal vitiligo, one patient with vitiligo vulgaris, and three patients with
      segmental vitiligo showed marked (grade 3) repigmentation. CONCLUSION: Marginal
      and central repigmentation with hyperpigmented borders was seen in the majority
      of lesions. Further controlled trials should be undertaken to evaluate the use of
      topical DPCP in vitiligo.

PMID- 19171991
TI  - Nocardial mycetoma: diverse clinical presentations.
AB  - Nocardia spp are gram-positive, aerobic, acid-fast bacteria which exist as
      saprophytes in nature. Invasive disseminated infections are particularly common
      in immunocompromised or debilitated hosts. Superficial infections with Nocardia
      spp occur as a result of local trauma and contamination of the wound. Clinically,
      it presents as acute infection (abscesses or cellulitis), mycetoma, or
      sporotrichoid infection. Differential diagnosis includes eumycetoma,
      chromomycosis, blastomycosis, coccidioidomycosis, sporotrichosis, tuberculosis,
      botryomycosis, syphilis, yaws, and neoplasia. Its diagnosis is confirmed by
      demonstrating the causative organism in exudates (as granules), tissue specimens,
      or cultures. Early diagnosis will obviate need for drastic surgical measures as
      early institution of chemotherapy is effective in most patients. However, its
      diagnosis is often delayed due to diverse clinical presentations and for want of
      clinical suspicion, particularly in non-endemic areas. This paper presents 4
      clinical forms of this not so uncommon disease, emphasizing the importance of
      high index of clinical suspicion, especially in non-endemic regions; and the
      significance of repeated examination of exudates for Nocardia granules for an
      early diagnosis.

PMID- 19171992
TI  - Diffuse cutaneous leishmaniasis: co-infection with human immunodeficiency virus
      (HIV).
AB  - Cutaneous leishmaniasis is a disease caused by intracellular protozoal parasites
      belonging to the genus Leishmania. Immune suppression caused by HIV infection is
      an important factor for atypical presentation and widespread progression of
      cutaneous leishmaniasis. Diffuse (disseminated) cutaneous leishmaniasis and HIV
      co-infection is emerging as an extremely serious new disease. A 38-year-old HIV
      positive man presented with a 12-month history of a progressive papule and
      nodular eruptions on face and extremities with infiltrations of nasal and oral
      mucosa. We report the case due to its atypical, widespread muco-cutaneous
      presentation masquerading as lepromatous leprosy.

PMID- 19171993
TI  - Berardinelli-Seip syndrome in a 6-year-old boy.
AB  - A 6-year-old boy presented with abnormal habitus since birth, delayed language
      development, history of frequent falls since 9 months, and fever since 1 week. He
      was found to have hyperandrogenic features, generalized paucity of fat,
      generalized muscular overdevelopment, and brownish pigmentation over the flexural
      creases. Skin biopsy demonstrated features suggestive of acanthosis nigricans
      with an absence of subcutaneous tissue. After further investigation, a diagnosis
      of Berardinelli-Seip syndrome with bilateral pneumonia and generalized tonic
      clonic seizures was made. Clinical features, histopathology, differential
      diagnosis, and prognosis of this rare disorder have been discussed.

PMID- 19171994
TI  - Clinicoepidemiological study of pityriasis rosea.

PMID- 19171995
TI  - Erythrokeratodermia variabilis: successful palliative treatment with acitretin.

PMID- 19171996
TI  - Granulomatous contact dermatitis to palladium following ear piercing.

PMID- 19171997
TI  - Primary cutaneous B-cell lymphoblastic lymphoma.

PMID- 19171998
TI  - Complete recovery from juvenile pemphigus vulgaris.

PMID- 19171999
TI  - Plica neuropathica: different etiologies in two cases.

PMID- 19172000
TI  - Linear verrucous hemangioma on the leg.

PMID- 19172001
TI  - Inflammatory nevus comedonicus in an infant.

PMID- 19172002
TI  - Osler-Weber-Rendu syndrome associated with vitiligo.

PMID- 19172003
TI  - Segmental vitiligo and twenty-nail dystrophy: an unusual association.

PMID- 19172004
TI  - Basal cell carcinoma occurring in a lesion of lichen planus: coincidence or
      causation?

PMID- 19172005
TI  - Type IV Ehlers-Danlos syndrome associated with factor VIII deficiency.

PMID- 19172006
TI  - Persistent atypical varicella in two renal transplant patients and its relation
      to mycophenolic acid.

PMID- 19172007
TI  - Scientific and linguistic precision in titles of papers published as original
      articles in Indian Journal of Dermatology, Venereology and Leprology.

PMID- 19172009
TI  - Langerhans cell histiocytosis presenting with hypopigmented macules.

PMID- 19172010
TI  - Lafora's disease diagnosed on axillary skin biopsy in 3 patients.

PMID- 19172011
TI  - Number of authors of single case reports in Indian Journal of Dermatology,
      Venereology and Leprology and Journal of the American Academy of Dermatology.

PMID- 19172012
TI  - Aggravation of psoriasis by antimalarials: a comment on the pathogenic mechanism.

PMID- 19172013
TI  - Predicted B-cell epitopes on 18 kDa antigen of Haemophilus ducreyi.

PMID- 19172014
TI  - Subcision in rolling acne scars with 24G needle.

PMID- 19172015
TI  - Furuncular myiasis mimicking pyoderma.

PMID- 19172016
TI  - Clinical applications of Q-switched NdYAG laser.

PMID- 19172017
TI  - Guidelines for writing a research project synopsis or protocol.

PMID- 19172018
TI  - Basics of statistics for postgraduates.

PMID- 19172019
TI  - An unusual periumbilical plaque.

PMID- 19172020
TI  - Obituary--Dr. B. C. Lahiri.

PMID- 19172023
TI  - Fate of medical dermatology in the era of cosmetic dermatology and
      dermatosurgery.

PMID- 19172024
TI  - Cosmeceuticals: are they truly worth the cost?

PMID- 19172025
TI  - Adverse reactions to cosmetics and methods of testing.
AB  - Untoward reactions to cosmetics, toiletries, and topical applications are the
      commonest single reason for hospital referrals with allergic contact dermatitis.
      In most cases, these are only mild or transient and most reactions being irritant
      rather than allergic in nature. Various adverse effects may occur in the form of
      acute toxicity, percutaneous absorption, skin irritation, eye irritation, skin
      sensitization and photosensitization, subchronic toxicity,
      mutagenicity/genotoxicity, and phototoxicity/photoirritation. The safety
      assessment of a cosmetic product clearly depends upon how it is used, since it
      determines the amount of substance which may be ingested, inhaled, or absorbed
      through the skin or mucous membranes. Concentration of ingredients used in the
      different products is also important. Various test procedures include in vivo
      animal models and in vitro models, such as open or closed patch test, in vivo
      skin irritation test, skin corrosivity potential tests (rat skin transcutaneous
      electrical resistance test, Episkin test), eye irritation tests (in vivo eye
      irritancy test and Draize eye irritancy test), mutagenicity/genotoxicity tests
      (in vitro bacterial reverse mutation test and in vitro mammalian cell chromosome
      aberration test), and phototoxicity/photoirritation test (3T3 neutral red uptake
      phototoxicity test). Finished cosmetic products are usually tested in small
      populations to confirm the skin and mucous membrane compatibility, and to assess
      their cosmetic acceptability.

PMID- 19172026
TI  - Diffuse hair loss in an adult female: approach to diagnosis and management.
AB  - Telogen effluvium (TE) is the most common cause of diffuse hair loss in adult
      females. TE, along with female pattern hair loss (FPHL) and chronic telogen
      effluvium (CTE), accounts for the majority of diffuse alopecia cases. Abrupt,
      rapid, generalized shedding of normal club hairs, 2-3 months after a triggering
      event like parturition, high fever, major surgery, etc. indicates TE, while
      gradual diffuse hair loss with thinning of central scalp/widening of central
      parting line/frontotemporal recession indicates FPHL. Excessive, alarming diffuse
      shedding coming from a normal looking head with plenty of hairs and without an
      obvious cause is the hallmark of CTE, which is a distinct entity different from
      TE and FPHL. Apart from complete blood count and routine urine examination,
      levels of serum ferritin and T3, T4, and TSH should be checked in all cases of
      diffuse hair loss without a discernable cause, as iron deficiency and thyroid
      hormone disorders are the two common conditions often associated with diffuse
      hair loss, and most of the time, there are no apparent clinical features to
      suggest them. CTE is often confused with FPHL and can be reliably differentiated
      from it through biopsy which shows a normal histology in CTE and miniaturization
      with significant reduction of terminal to vellus hair ratio (T:V < 4:1) in FPHL.
      Repeated assurance, support, and explanation that the condition represents
      excessive shedding and not the actual loss of hairs, and it does not lead to
      baldness, are the guiding principles toward management of TE as well as CTE. TE
      is self limited and resolves in 3-6 months if the trigger is removed or treated,
      while the prognosis of CTE is less certain and may take 3-10 years for
      spontaneous resolution. Topical minoxidil 2% with or without antiandrogens,
      finestride, hair prosthesis, hair cosmetics, and hair surgery are the
      therapeutically available options for FPHL management.

PMID- 19172027
TI  - Trace element levels in alopecia areata.
AB  - BACKGROUND: Alopecia areata (AA) is a recurrent, nonscarring type of hair loss
      considered to be an autoimmune process. Though its etiopathology is not fully
      understood, there are claims that imbalance of trace elements may trigger the
      onset of AA. AIM: The aim of the present study was to assess the levels of zinc,
      copper, and magnesium in the serum of AA patients. METHODS: Fifty AA patients (34
      men and 16 women), and fifty age and sex matched healthy control subjects were
      studied. Samples were analyzed using atomic absorption spectrometric methods.
      RESULTS: Serum zinc levels were significantly decreased (P < 0.05) in AA patients
      whose disease was extensive, prolonged, and resistant to treatment, whereas serum
      copper and magnesium levels showed insignificant rise compared to controls.
      CONCLUSION: We conclude that copper and magnesium levels are not altered in AA,
      but the decreased zinc levels found in our study may merit further investigation
      of the relationship.

PMID- 19172028
TI  - Teledermatology: clinical case profiles and practical issues.
AB  - BACKGROUND AND AIMS: Teledermatology is an area that has shown rapid growth in
      the recent past. However, not many studies have been conducted with regards to
      the application of teledermatology in India. Aim of our study was to evaluate the
      clinical profiles of cases referred for teledermatology consultation at our
      center, and to assess and compare the different modalities of teledermatology
      consultations done at our center along with the practical issues related to such
      a service. METHODS: A retrospective study of teledermatology consultations at our
      center over a 3-year period was carried out. Store-and-forward (SAF), realtime
      consults (RTC), and hybrid (combining the two) were included.Two trained
      dermatologists were involved in carrying out the consultations in the referral
      center. RESULTS: Of the 120 consultations, 68 male and 52 female patients in the
      age range of 2-77 years were seen. In more than 90% of the cases,
      teleconsultation was the first contact for the patient with the dermatologist
      (for the present condition). In 68% of the cases, the reference was for both
      diagnosis and management, while in the rest, the reference was mainly related to
      management issues (appropriate diagnosis having already been made). Certainity of
      diagnosis was maximum for hybrid, SAF, and RTC. CONCLUSIONS: Teledermatology can
      prove valuable as a tool to provide healthcare in areas of shortage of
      specialists. A hybrid system combining SAF and RTC could be the ideal form of
      teledermatology consultations in the future. Many practical issues need to be
      addressed before the effectiveness of teledermatology in India can be fully
      recognized.

PMID- 19172029
TI  - Presentation of early onset psoriasis in comparison with late onset psoriasis: a
      clinical study from Pakistan.
AB  - BACKGROUND: Early onset psoriasis and late onset psoriasis are known to have
      different clinical patterns in Caucasian population. However, there is paucity of
      data among Asian patients. AIMS: To compare the clinical presentation of early
      onset psoriasis with late onset psoriasis in Pakistani population. METHODS:
      During the study period, participating dermatologists filled a pre-tested
      questionnaire for each patient with psoriasis on first encounter. The
      questionnaire incorporated information regarding clinical and demographic
      features of psoriasis including age of onset, clinical type of psoriasis, nail or
      joint involvement, and PASI score. Patients were then divided into early onset
      (age of onset < 30 years, group I) and late onset (age of onset > or =30 years,
      group II) psoriasis. RESULTS: Five hundred and fifteen questionnaires were filled
      and returned for evaluation. There was no statistically significant difference in
      both groups with regards to gender, family history (P = 0.09), nail (P = 0.69)
      and joint (P = 0.74) involvement, disease severity (P = 0.68), and clinical type
      of psoriasis (P = 0.06). No significant difference between disease severities
      measured by PASI score was observed in the two groups (P = 0.68). Presence of
      nail involvement was associated with joint disease in both groups (odds ratio
      2.8, confidence interval 1.9-4.1). CONCLUSION: Patients with early and late onset
      psoriasis in Pakistani population do not show different clinical and demographic
      features contrary to the Western patients.

PMID- 19172030
TI  - Male sex workers: are we ignoring a risk group in Mumbai, India?
AB  - BACKGROUND: Male sex workers (MSWs) have recently been recognized as an important
      risk group for sexually transmitted infections (STIs) including human
      immunodeficiency virus (HIV) infection. Although there are global studies on
      MSWs, few such studies describe the behavioral patterns and STIs among this
      population in India. METHODS: MSWs were evaluated at the Humsafar trust, a
      community based organization situated in suburban Mumbai, India. We report on the
      demographics, sexual behaviors, and STIs including HIV of these sex workers.
      RESULTS: Of the 75 MSWs, 24 were men and 51 were transgenders. The mean age of
      the group was 23.3 (+ 4.9) years. About 15% were married or lived with a
      permanent partner. Of these individuals, 85% reported sex work as a main source
      of income and 15% as an additional source. All the individuals reported anal sex
      (87% anal receptive sex and 13% anal insertive sex). About 13% of MSWs had never
      used a condom. The HIV prevalence was 33% (17% in men vs 41% in transgenders, P =
      0.04). The STI prevalence was 60% (58% in men vs 61% in transgenders, P = 0.8).
      Syphilis was the most common STI (28%) in these MSWs. HIV was associated with
      being a transgender (41 vs 17%, P = 0.04), age > 26 years (57 vs 28%, P = 0.04),
      more than one year of sex work (38 vs 8%, P = 0.05), and income P = 0.02).
      CONCLUSIONS: The MSWs have high-risk behaviors, low consistent condom use, and
      high STI/HIV infections. These groups should be the focus of intensive public
      health interventions aimed at reduction of risky sexual practices, and STI/HIV
      prevention and care.

PMID- 19172031
TI  - Comparing the therapeutic effects of finasteride gel and tablet in treatment of
      the androgenetic alopecia.
AB  - BACKGROUND: Finasteride, a type II-selective 5alpha-reductase inhibitor, as a
      causative agent of decreasing dihydroxy testosterone (DHT) level, is effective in
      the treatment of male androgenic alopecia. AIM: We compared the local and oral
      finasteride in the treatment of androgenic alopecia. METHOD: This is a double
      blind, randomized clinical trial study of 45 male patients, who were referred
      with alopecia to the private clinics and departments in Boo-Ali Sina Hospital, in
      Sari. Patients with male androgenic alopecia were selected according to the
      history and physical examinations. The patients were randomly divided into two:
      topical finasteride (A) and oral finasteride (B) groups. Topical finasteride
      group (A) received a topical gel of 1% finasteride and placebo tablets, while the
      oral finasteride group (B) received finasteride tablets (1 mg) and gel base
      (without drug) as placebo for 6 months. The patients were followed by clinical
      observation and recording of side effects prior to the treatment and at the end
      of first week, and then by a monthly follow-up. The size of bald area, total hair
      count, and terminal hair were studied. Data were analyzed by descriptive and Chi
      square statistical test. RESULTS: The mean duration of hair loss was 18.8+/-23.10
      months. Each month the terminal hair, size of bald area and hair count between
      the two groups were compared. There were no significant differences between the
      two groups as a viewpoint of hair thickness, hair counts and the size of bald
      area. Serial measurements indicated a significant increase in hair counts and
      terminal hair counts between the two groups. CONCLUSIONS: The results of this
      study showed that the therapeutic effects of both finasteride gel and finasteride
      tablet were relatively similar to each other.

PMID- 19172032
TI  - The rK39 immunochromatic dipstick testing: a study for K39 seroprevalence in dogs
      and human leishmaniasis patients for possible animal reservoir of cutaneous and
      visceral leishmaniasis in endemic focus of Satluj river valley of Himachal
      Pradesh (India).
AB  - BACKGROUND: The newly recognized endemic focus of leishmaniasis in Satluj river
      valley of Himachal Pradesh (India) has both localized cutaneous leishmaniasis
      (LCL) and visceral leishmaniasis (VL) predominantly caused by Leishmania
      donovani. Rapid rK39 immunochromatographic dipstick test detects circulating
      antibodies to recombinant K39 antigen of L. donovani-infantum complex and is
      highly specific/sensitive in diagnosing symptomatic or asymptomatic infection in
      humans and dogs. METHODS: The sera from two VL patients and 13 LCL patients, and
      31 dogs were subjected to rK39 immunochromatographic dipstick testing with an aim
      to identify possible animal reservoir for leishmaniasis in this endemic focus.
      RESULTS AND CONCLUSION: The positive rapid rK39 immunochromatographic dipstick
      test in 100% VL and 31.8% LCL patients, and 6.5% dogs suggests that both VL and
      LCL in this focus are apparently being caused by L. donovani-infantum and that
      reservoir infection is perhaps being chiefly maintained in asymptomatic dogs.
      However, it needs corroborative evidence in the form of in-vitro parasite
      cultivation and/or PCR studies for confirmation. A more elaborate study is
      recommended.

PMID- 19172033
TI  - Generalized morphea, lichen sclerosis et atrophicus associated with oral
      submucosal fibrosis in an adult male.
AB  - Generalized morphea is a disease characterized by wide-spread sclerosis of the
      skin. A 39-year-old man presented with history of multiple pigmented and bound
      down plaques on the body along with mucosal involvement. Dermatological
      examination showed multiple indurated and sclerosed plaques with follicular
      plugging in few of them and gross thickened eroded and glazed tongue. The
      constellation of these findings with histopathological correlation led us to
      diagnosis of this spectrum of cutaneous involvement. The coexistence of localized
      morphea with lichen sclerosis et atrophicus has been reported earlier but
      existence of these entities with submucosal fibrosis in a same patient is
      documented here and is the first of its kind.

PMID- 19172034
TI  - Retiform hemangioendothelioma with lymph node metastasis: a rare entity.
AB  - Retiform hemangioendothelioma (RH) is a rare, recently described, unique kind of
      low grade angiosarcoma. The tumor is characterized by distinctive arborizing
      blood vessels that mimic the appearance of rete testis. The tumor chiefly
      originates from the skin and subcutaneous tissue and has a tendency to recur
      locally. Only one case with lymph node metastasis has been reported previously.
      Another such rare case of RH is being reported in an adult female who presented
      with a subcutaneous nodule, underwent multiple recurrences and uniquely
      metastasized to regional lymph node.

PMID- 19172035
TI  - Nephrogenic fibrosing dermopathy.
AB  - An adult female patient on hemodialysis for chronic renal failure presented with
      large, brownish, and indurated plaques with bound-down skin on both lower limbs
      and abdomen along with difficulty in movement of the legs. Histopathological
      features revealed thick collagen bundles admixed with mucin and intercalating
      spindle-like cells characteristic of nephrogenic fibrosing dermopathy (NFD).
      Immunohistochemical study showed prominent CD68 positivity and weak CD34
      positivity suggesting that the plaques were more than 20-weeks old. NFD in
      patients with chronic renal failure of unknown cause is a poor prognostic
      indicator. Early detection before the development of contracture and prompt
      treatment of NFD and underlying renal failure may reverse this disabling
      condition.

PMID- 19172036
TI  - Disseminated cutaneous rhinosporidiosis: varied morphological appearances on the
      skin.
AB  - Rhinosporidiosis is a chronic granulomatous disorder caused by Rhinosporidium
      seeberi . It frequently involves the nasopharynx and occasionally affects the
      skin. We report a case of 45-year-old man who had disseminated cutaneous
      rhinosporidiosis with cutaneous pseudohorn, its base arising from
      rhinosporidiosis. The case presented with multiple reddish lesions over the nose
      of six years duration. In the past year, he developed skin lesions over the left
      arm, forearm, back, and chest. On examination, polymorphic lesions of
      rhinosporidiosis in form of verrucous plaque, unulcerated tumor, granulomatous
      growth, and furunculoid lesions were observed. Interestingly, there was a
      cutaneous horn over the chest which on histopathological examination showed
      hyperplastic epithelium with numerous globular cysts of varying shape,
      representing sporangia in different stages of development and transelimination.
      Computerized tomography scan of the chest showed bilateral opacities suggestive
      of lung involvement. On the basis of these clinical and histopathological
      findings, a diagnosis of nasal rhinosporidiosis with cutaneous and systemic
      dissemination was made.

PMID- 19172037
TI  - Periungual acquired digital fibrokeratoma.

PMID- 19172038
TI  - The reliability of periodic acid-Schiff staining in the diagnosis of
      onychomycosis.

PMID- 19172039
TI  - Granulomatous rosacea in Cornelia de Lange syndrome.

PMID- 19172040
TI  - Tanning caused by psoralen-photochemotherpy in Indian skin.

PMID- 19172041
TI  - Concurrent oral and genital involvement in lichen planus.

PMID- 19172042
TI  - Noncicatricial alopecia due to plaque-type psoriasis of the scalp.

PMID- 19172043
TI  - Localized pemphigus vulgaris on cheeks responding to topical steroids.

PMID- 19172044
TI  - Chrysomya bezziana infestation in a neglected squamous cell carcinoma on the
      face.

PMID- 19172045
TI  - Pulse therapy for pemphigus: the burden of proof.

PMID- 19172046
TI  - Prolonged antimicrobial and oral cyclophosphamide therapy in pemphigus: need for
      caution.

PMID- 19172047
TI  - Emergence of dermatology in India.

PMID- 19172048
TI  - Fitzpatrick skin typing: applications in dermatology.

PMID- 19172049
TI  - Asymptomatic swelling in a 60-year-old scar.

PMID- 19172051
TI  - Cytomegalovirus infection: an Indian perspective.
AB  - Human cytomegalovirus (CMV) poses an important public health problem as it may
      cause serious morbidity and mortality in congenitally infected newborns and
      immunocompromised patients, most notably transplant recipients and HIV-infected
      persons. It is probably one of the most common infections known to humans and is
      characterized by a self-limiting infection in healthy individuals. CMV infection
      is the single most frequent cause of infectious complications in the early period
      following kidney transplantation Post-transfusion cytomegalovirus infection is of
      concern in the immunocompetent as well as in certain categories of
      immunocompromised individuals such as neonates, pregnant women, recipients of
      bone marrow and other organ transplants and individuals with immunodeficiency
      disorders. The emergence of AIDS in India has necessitated the establishment of
      reliable tests for diagnosis of cytomegalovirus infection as a damaged immune
      system permits cytomegalovirus reactivation. The magnitude of this problem in
      India and the various diagnostic modalities used have not been adequately
      investigated and, hence, CMV infection is still a major health problem warranting
      strong preventive measures. The ultimate goal of the prevention program is to
      develop a vaccine that can be administered to seronegative women of childbearing
      age to prevent primary infection during pregnancy.

PMID- 19172052
TI  - Prevalence of hepatitis C virus (HCV) coinfection in HIV infected individuals in
      south India and characterization of HCV genotypes.
AB  - PURPOSE: To determine anti-HCV antibodies and genomic subtype of HCV in 1487
      confirmed human immunodeficiency virus (HIV) positive samples. METHODS: A total
      of 1487 confirmed HIV-positive samples were tested for anti-HCV antibodies by
      using a third generation ELISA kit (Ortho 3.0) and by RT PCR for HCV. HIV and HCV
      coinfected samples were selected for HCV genotyping by RFLP and subtyping with
      NS5-type specific primers. RESULTS: A total of 1487 HIV-infected serum samples
      were screened for HCV infection, of which, a 1443 (97.04%) were negative and 45
      (3.02%) were coinfected. HIV-HCV coinfection was predominant in the age group 41
      50 years (51.1%). HCV genotyping and subtyping was done for the 45 HCV RNA
      positive specimens of which genotype 1 was observed in 31 (68.8%) and genotype 3
      was observed in 14 (31.1%) subjects. Further subtyping analysis showed the
      genotype 1b in 23 (51.1%), 1a in eight (17.7%), 3a in 10 (22.2%) and 3b in four
      (8.8%) subjects. CONCLUSION: HIV and HCV seroprevalence is higher in South India,
      and the most prevalent genotype in coinfection was genotype 1b.

PMID- 19172053
TI  - Maternal and neonatal screening for Group B streptococci by SCP B gene based PCR:
      a preliminary study.
AB  - OBJECTIVE: To detect the magnitude of group B streptococcal (GBS) colonization
      and disease among a sample of pregnant women and their infants in Egypt. STUDY
      DESIGN: Prospective observational study. PARTICIPANTS: The study included 95
      pregnant females, 35-37 weeks of gestational age, attending the antenatal
      outpatient clinic at AlFayom University Hospital between September 2006 and June
      2007. All participants were screened with vaginorectal swabs by a conventional
      GBS PCR assay. Participants were grouped into group A (GBS present, 17 patients)
      and group B (GBS absent, 78 patients). Details with regard to labor and delivery
      were recorded and placental pathology was examined to detect histological
      chorioamnionitis. Ninety-five infant data were also recorded. All neonates of
      group A (17 out of 95 with known positive maternal GBS) underwent collection of
      simultaneous specimens from surface sites for PCR before their first bath and
      within four hours of birth. RESULTS: GBS carriage rate in the study sample was
      17.89%. Chorioamnionitis confirmed in three patients by placental pathology (one
      was in group A and two in group B) was statistically not significant. Twenty-two
      women had rupture of membranes (< 12 hours) before delivery (four from group A
      and 18 from group B) that was not statistically significant. There were three
      infants out of 17 in group A who had GBS colonized at one or more sites by PCR
      which was statistically significant. However, only one infant was admitted to
      neonatal intensive care unit (NICU) that was not statistically significant.
      CONCLUSION: Maternal GBS carriage is associated with a significant increase in
      neonatal infection rate but is not associated with an increase in neonatal
      intensive care admission. An accurate evaluation of colonization rate (using a
      larger sample) is desired to evaluate neonatal invasive disease and determine the
      cost effectiveness of PCR to select an appropriate preventive strategy in Egypt.

PMID- 19172054
TI  - A molecular method for typing Herpes simplex virus isolates as an alternative to
      immunofluorescence methods.
AB  - BACKGROUND: Typing of Herpes simplex virus (HSV) isolates is required to identify
      the virus isolated in culture. The methods available for this include antigen
      detection by immunofluorescence (IF) assays and polymerase chain reaction (PCR).
      This study was undertaken to standardize a molecular method for typing of HSV and
      compare it with a commercial IF reagent for typing. OBJECTIVES: To compare a
      molecular method for typing HSV isolates with a monoclonal antibody (MAb) based
      IF test. STUDY DESIGN: This cross-sectional study utilized four reference strains
      and 42 HSV isolates obtained from patients between September 1998 and September
      2004. These were subjected to testing using an MAb-based IF test and a PCR that
      detects the polymerase ( pol ) gene of HSV isolates. RESULTS: The observed
      agreement of the MAb IF assay with the pol PCR was 95.7%. Fifty four point eight
      percent (23/42) of isolates tested by IF typing were found to be HSV-1, 40.5%
      (17/42) were HSV-2, and two (4.8%) were untypable using the MAb IF assay. The two
      untypable isolates were found to be HSV-2 using the pol PCR. In addition, the
      cost per PCR test for typing is estimated to be around Rs 1,300 (USD 30), whereas
      the cost per MAb IF test is about Rs 1,500 (USD 35) including all overheads
      (reagents, instruments, personnel time, and consumables). CONCLUSION: The pol PCR
      is a cheaper and more easily reproducible method for typing HSV isolates as
      compared to the IF test. It could replace the IF-based method for routine typing
      of HSV isolates as availability of PCR machines (thermal cyclers) is now more
      widespread than fluorescence microscopes in a country like India.

PMID- 19172055
TI  - Comparison of cefoxitin disc diffusion test, oxacillin screen agar, and PCR for
      mecA gene for detection of MRSA.
AB  - Cefoxitin is a potent inducer of the mecA regulatory system. It is being
      recommended for detection of methicillin resistance in Staphylococcus aureus
      (MRSA) when using disk diffusion testing. The aim of our study was to evaluate
      the efficacy of cefoxitin disc diffusion test to characterize MRSA and compare it
      with oxacillin agar screening and detection of mecA gene by PCR. MATERIALS AND
      METHODS: Fifty strains of S. aureus isolated from clinical samples were used in
      the study. Routine antibiotic susceptibility testing was performed including
      oxacillin disk. Oxacillin screen agar plates with 4% NaCl and 6 microg/ml of
      oxacillin were inoculated and interpreted as per standard guidelines. Cefoxitin
      disc diffusion test was performed using 30 microg disc and zone sizes were
      measured. PCR for amplification of the mecA gene was performed. RESULTS: Out of
      the 50 isolates, 28 were found to be methicillin resistant by oxacillin disc
      diffusion test, 30 were resistant by oxacillin screen agar method, and 32 were
      resistant with cefoxitin disc diffusion. For these 32 isolates mecA gene was
      positive. CONCLUSION: Results of cefoxitin disc diffusion test is in concordance
      with the PCR for mecA gene. Thus, the test can be an alternative to PCR for
      detection of MRSA in resource constraint settings.

PMID- 19172056
TI  - In vitro inhibition of Helicobacter pylori urease with non and semi fermented
      Camellia sinensis.
AB  - PURPOSE: Helicobacter pylori is the etiological agent in duodenal and peptic
      ulcers. The growing problem of antibiotic resistance by the organism demands the
      search for novel compounds, especially from natural sources. This study was
      conducted to evaluate the effect of Camellia sinensis extracts on the urease
      enzyme that is a major colonization factor for H. pylori. METHODS: Minimum
      inhibitory concentrations of nonfermented and semifermented C. sinensis methanol:
      water extracts were assessed by broth dilution method. Examination of the urease
      function was performed by Mc Laren method, and urease production was detected on
      12% SDS polyacrylamide gel electrophoresis from whole cell and membrane bound
      proteins. RESULTS: Both extracts had inhibitory effects against H. pylori and
      urease production. At a concentration of 2.5 mg/ml of nonfermented extract and
      3.5 mg/ml of semifermented extract the production of Ure A and Ure B subunits of
      the urease enzyme were inhibited completely. A concentration of 4 mg/ml of
      nonfermented and 5.5 mg/ml of semifermented extract were bactericidal for H.
      pylori. CONCLUSIONS: C. sinensis extracts, especially the nonfermented, could
      reduce H. pylori population and inhibit urease production at lower
      concentrations. The superior effect of nonfermented extract is due to its rich
      polyphenolic compounds and catechin contents.

PMID- 19172057
TI  - In vitro culture of various species of microsporidia causing keratitis:
      evaluation of three immortalized cell lines.
AB  - Being intracellular parasites, microsporidia can only be propagated in cell
      culture systems. This study evaluated three cell lines to determine the most
      suitable host-parasite In vitro system. Confluent monolayers of vero, SIRC, and
      HeLa cell lines, grown in 24-well tissue culture plates, were inoculated with
      varying concentrations (1 x 10(4) to 1 x 10(8) spores/mL) of Vittaforma corneae,
      Encephalitozoon hellem, Encephalitozoon cuniculi, and Encephalitozoon
      intestinalis spores. Growth was compared quantitatively at weekly intervals.
      Encephalitozoon species showed the highest amount of growth when cultured in vero
      cell line, while there was no significant difference in their growth in SIRC and
      HeLa cell lines. In comparison, V. corneae showed the highest growth in SIRC
      cells, followed by vero cells. The analytical sensitivity was found to be 1 x
      10(4) spores/mL for vero cell line compared to 1 x 10(5) spores/mL for SIRC cell
      line and 1 x 10(7) spores/mL for HeLa cell line. HeLa cells also showed rapid
      disruption of cells, and the spores could not be easily distinguished from cell
      debris. This is the first report of the comparison of vero, SIRC, and HeLa for
      the propagation of microsporidial spores. Vero cell line was found to be more
      sensitive than SIRC and HeLa cells, and we believe that the inclusion of vero
      cell line in the routine culture protocols of ocular parasitology laboratories
      would result in a significant increase in the diagnostic yield.

PMID- 19172058
TI  - Investigation of T cell receptors in the peripheral blood of patients with active
      pulmonary tuberculosis.
AB  - T cells have the capability of recognizing target cells through their T cell
      receptors (TCRs). Thus, the percentages of CD3+/gamma-delta (gammadelta) TCR+ and
      CD3+/alpha-beta (alphabeta) TCR+ T lymphocytes were investigated in active and
      inactive pulmonary tuberculosis (PT) patients and in healthy individuals. CD3+
      and CD3+/alphabeta TCR+ cell percentages were significantly lower in all PT
      patients than in healthy subjects. Percentages of CD3+/gammadelta and
      CD3+/alphabeta TCR+ were not statistically different between active and inactive
      PT patients. It was concluded that alphabeta TCR+ T cells might have a protective
      role in tuberculosis infection.

PMID- 19172059
TI  - Needle stick injuries in a tertiary care hospital.
AB  - BACKGROUND: Accidental needle stick injuries (NSIs) are an occupational hazard
      for healthcare workers (HCWs). A recent increase in NSIs in a tertiary care
      hospital lead to a 1-year review of the pattern of injuries, with a view to
      determine risk factors for injury and potential interventions for prevention.
      METHODS: We reviewed 1-year (July 2006-June 2007) of ongoing surveillance of
      NSIs. RESULTS: The 296 HCWs reporting NSIs were 84 (28.4%) nurses, 27 (9.1%)
      nursing interns, 45 (21.6%) cleaning staff, 64 (21.6%) doctors, 47 (15.9%)
      medical interns and 24 (8.1%) technicians. Among the staff who had NSIs, 147
      (49.7%) had a work experience of less than 1 year (n = 230, 77.7%). In 73 (24.6%)
      of the NSIs, the patient source was unknown. Recapping of needles caused 25
      (8.5%) and other improper disposal of the sharps resulted in 55 (18.6%) of the
      NSIs. Immediate post-exposure prophylaxis for HCWs who reported injuries was
      provided. Subsequent 6-month follow-up for human immunodeficiency virus showed
      zero seroconversion. CONCLUSION: Improved education, prevention and reporting
      strategies and emphasis on appropriate disposal are needed to increase
      occupational safety for HCWs.

PMID- 19172060
TI  - High prevalence of hepatitis A virus antibody among Bangladeshi children and
      young adults warrants pre-immunization screening of antibody in HAV vaccination
      strategy.
AB  - Serum samples from 465 subjects aged between 1 and 25 years were tested for
      antibody against hepatitis A virus (HAV) [anti-HAV IgG and IgM] to determine the
      seroprevalence of HAV antibody and do a cost-benefit analysis for decision making
      about vaccination against HAV among the general population of Bangladesh. A high
      prevalence of anti-HAV (74.8%) was observed in the study population; the whole
      study population was found positive for anti-HAV by the age of 25 years. On
      performing the cost-benefit analysis, it was found that the cost for vaccination
      with screening for anti-HAV was almost three times cheaper than vaccination
      without screening. Thus, in the present socioeconomic condition of Bangladesh, a
      policy based on screening for HAV antibody before vaccination is recommended.

PMID- 19172061
TI  - SHV-28, an extended-spectrum beta-lactamase produced by a clinical isolate of
      Klebsiella pneumoniae in south India.
AB  - SHV-28, an extended spectrum beta-lactamase from a clinical isolate of Klebsiella
      pneumoniae , had an isoelectric point of 7.6 and a substrate profile showing
      preferential hydrolysis for cefotaxime over ceftazidime. It differed from SHV-1
      by one amino acid substitution. The conserved S-T-F-K and K-T-G motifs were
      identified by SHV-28 protein sequencing.

PMID- 19172062
TI  - Differentiation of Candida dubliniensis on chrom agar and Pal's agar.
AB  - Difference in expression of putative virulence factors and in antifungal
      susceptibility among different Candida species has raised the need for species
      level identification. The close relationship of Candida dubliniensis with C.
      albicans has led to misidentification of C. dubliniensis isolates as C. albicans.
      Phenotypic tests include ability to produce chlamydospore on casein agar, colony
      colour development on differential media CHROM agar Candida medium and ability to
      form hyphal fringe on Pal's agar, have been used to differentiate these two
      Candida species. Fifty isolates of Candida species were recovered from various
      specimens (blood, urine, tissue and respiratory secretions) from diabetic and
      cancer patients between April and July 2007. The isolates were tested for
      chlamydospore production on casein agar. These were also streaked simultaneously
      on CHROM agar, Pal's agar and a combination of CHROM agar supplemented with Pal's
      agar for identification and differentiation of C. dubliniensis from C. albicans.
      On CHROM agar, 19 isolates were identified as C. dubliniensis, nine as C.
      albicans, 10 as C. krusei, nine as C. tropicalis and two as C. glabrata. One was
      indeterminate and later identified as C. dubliniensis. Out of the 20 C.
      dubliniensis isolates, 19 isolates exhibited hyphal fringe on Pal's agar. On
      CHROM agar supplemented with Pal's agar, 16 out of the 19 fringe-positive
      isolates exhibited fringe surrounding the bluish green-coloured colonies of C.
      dubliniensis. Additional identification tests like growth at 45 degrees C and
      ability to reduce 2,3,5-triphenyltetrazolium chloride were time efficient,
      inexpensive and easy-to-use methods for differentiation of C. dubliniensis and C.
      albicans isolates. CHROM agar when supplemented with Pal's agar gave definitive
      identification between C. dubliniensis and C. albicans.

PMID- 19172063
TI  - The risk factors and outcome of fungal peritonitis in continuous ambulatory
      peritoneal dialysis patients.
AB  - AIM: To determine the risk factors and outcome of fungal peritonitis in
      continuous ambulatory peritoneal dialysis (CAPD) patients over a 7-year period.
      PATIENTS AND METHODS: This retrospective study was conducted on 30 cases of
      fungal peritonitis in CAPD patients during a 7-year period (2000-2007). The
      diagnosis was based on elevated CAPD effluent count and isolation of fungi.
      Patients were evaluated for previous episode of bacterial peritonitis. RESULTS:
      The incidence of fungal peritonitis was 16.2%. Age varied between 8 and 75 years,
      with a mean age of 57 years. Twenty-three were males (76.7%) and seven were
      females (23.3%). Seventeen patients (56.6%) had previous episodes of bacterial
      peritonitis that was treated with multiple antibiotics. The common fungus was
      Candida species (50%). CAPD catheter removal and initiation of antifungal therapy
      was done for all patients. Reinsertion was done for three (10%) patients.
      Mortality rate was 20%. CONCLUSION: Patients with previous bacterial peritonitis
      and antibiotic usage are at greater risk of developing fungal peritonitis.

PMID- 19172064
TI  - Screening for methicillin-resistant Staphylococcus aureus carriers among patients
      and health care workers of a tertiary care hospital in south India.
AB  - A total of 200 subjects were screened for carriage of methicillin-resistant
      Staphylococcus aureus (MRSA) at different sites using oxacillin blood agar and
      mannitol salt agar with oxacillin. Overall carriage rate was 8.5%, with the
      highest rate in inpatients (15.6%) while the lowest was seen in health care
      workers (1.8%). The commonest site of colonization was the anterior nares.
      Oxacillin blood agar was found to be superior to mannitol salt agar with
      oxacillin for the isolation of MRSA. Male sex and prolonged hospital stay were
      found to be the major risk factors for MRSA colonization.

PMID- 19172065
TI  - Isolation of Salmonella enterica serotype Isangi from a suspected case of enteric
      encephalopathy.
AB  - Nontyphoidal salmonella species are thought to be potentially infectious to
      humans and many are documented to cause human diseases. We isolated S. Isangi
      from the blood of a 30-year-old man with complaints of diarrhoea, fever, and
      altered sensorium. The serotype of the isolate was confirmed at National
      Salmonella Centre (Vet.), Division of Bacteriology and Mycology, Indian
      Veterinary Research Institute, Izzatnagar, India. The isolate was not an extended
      spectrum beta-lactamase (ESBL) producer and the patient responded well to
      ceftriaxone. We reviewed the literature concerning infections caused by
      salmonella; however, did not find any report related to S. Isangi infection in
      human beings from India.

PMID- 19172067
TI  - Bilateral breast abscess: a rare complication of enteric fever.
AB  - Breast abscess is usually caused by Staphylococcus aureus in pregnant or
      lactating females. Salmonella spp. is occasionally associated with abscess
      formation in various organs, but breast abscess is a very rare complication. In
      enteric fever dissemination to multiple organ systems following bacteraemia can
      lead to localized abscess. We report a case of bilateral breast abscess due to
      Salmonella Typhi in an unmarried 35-year-old female without any predisposing
      conditions. She presented with fever and painful swelling of both the breasts. S.
      typhi was isolated from both breasts. Such rare cause must be suspected in
      females without any evident predisposing factors for effective management.

PMID- 19172066
TI  - Phaeohyphomycosis of subcutaneous tissue caused by Phaeoacremonium parasiticum.
AB  - Though Phaeoacremonium parasiticum is an unusual cause of human disease,
      subcutaneous infection, eumycetoma, osteomyelitis, arthritis and even
      disseminated diseases, such as fungemia and endocarditis have been reported.
      Here, we report a case of subcutaneous abscess on the forearm due to P.
      parasiticum in a 26-year-old woman. There were no obvious predisposing factors.
      The patient was treated with surgical debridement followed by intravenous
      amphotericin B and itraconazole to which she responded well. We report this case,
      being rare and the first from India.

PMID- 19172068
TI  - Cerebral Candida abscess in an infant.
AB  - Brain abscess is uncommon in the pediatric population. Here, we report one such
      case due to Candida albicans in one-year-old infant, without any predisposing
      factors. The child presented with progressively increasing size of head
      circumference. The diagnosis was confirmed by CT scan of brain and
      microbiological investigations on the drained pus material. The patient responded
      to combination of surgery (drainage) and intravenous amphotericin B. Neurological
      development six months after hospital discharge was normal. The organism being a
      rare cause of cerebral abscess in pediatric population is reported here.

PMID- 19172069
TI  - Tuberculous synovitis in a HIV positive patient.
AB  - Tuberculosis of the appendicular skeleton is an uncommon infection by tubercle
      bacilli. Thirty percent of the skeletal tuberculosis involves joints, the knee
      being the third most common joint affected. We report a case of tubercular
      synovitis of the knee joint in a 30-year-old HIV seropositive male. The diagnosis
      was done by Ziehl-Neelsen stain and culture on Lowenstein Jensen medium, of the
      synovial fluid along with the X-ray findings of the knee joint. The X-ray of the
      chest showed findings suggestive of pulmonary tuberculosis. The patient was
      responding well to the antitubercular treatment at the last follow up.

PMID- 19172070
TI  - A case of tuberculous pericardial effusion.
AB  - Tuberculosis accounts for up to 4% of acute pericarditis and 7% cases of cardiac
      tamponade. Prompt treatment can be life saving but requires accurate diagnosis.
      We report a case of 30-year-old male who presented with fever, chills, and dry
      nonproductive cough since one month. The case was diagnosed by radiological
      findings, which were suggestive of pulmonary tuberculosis, followed by acid fast
      staining and culture of the aspirated pericardial fluid. The patient was
      responding to antitubercular treatment at the last follow up.

PMID- 19172071
TI  - Giant Mantoux reaction.

PMID- 19172072
TI  - Comparison of conventional broth blood culture technique and manual lysis
      centrifugation technique for detection of fungemia.

PMID- 19172073
TI  - Hepatitis B virus and human immunodeficiency virus infections are a public health
      problem even in rural communities of Vellore district, Tamil Nadu.

PMID- 19172074
TI  - Intestinal helminths and associated risk factors in children of district Pulwama,
      Kashmir, India.

PMID- 19172076
TI  - Writing pens as fomites in hospital.

PMID- 19172075
TI  - Sedimentation method, a good alternative to centrifugation for concentration of
      acid fast bacilli in developing countries: a preliminary study from western Uttar
      Pradesh.

PMID- 19172077
TI  - Visceral leishmaniasis simulating chronic liver disease: successful treatment
      with miltefosine.

PMID- 19172078
TI  - Nasopharyngeal carriage and antibiotic resistance of Haemophilus influenzae,
      Streptococcus pneumoniae and Moraxella catarrhalis in healthy school children in
      Turkey.

PMID- 19172079
TI  - In vitro interactions between cotrimoxazole and doxycycline in Burkholderia
      pseudomallei: how important is this combination in maintenance therapy of
      melioidosis?

PMID- 19172080
TI  - Prostatic abscess by Staphylococcus aureus in a diabetic patient.

PMID- 19172081
TI  - A comparison of association statistics between pooled and individual genotypes.
AB  - BACKGROUND: Markers for individual genotyping can be selected using quantitative
      genotyping of pooled DNA. This strategy saves time and money. METHODS: To
      determine the efficacy of this approach, we investigated the bivariate
      distribution of association test statistics from pooled and individual genotypes.
      We used a sample of approximately 1,000 samples with individual and pooled
      genotyping on 40,000 SNPs. RESULTS AND CONCLUSIONS: We found that the
      distribution of the joint test statistics can be modelled as a mixture of two
      bivariate normal distributions. One distribution has a correlation of zero, and
      is probably due to SNPs whose pooled genotyping was unsuccessful. The other
      distribution has a correlation of approximately 0.65 in our data. This latter
      distribution is probably accounted for by SNPs whose pooled genotyping accurately
      predicts the underlying allele frequency. Approximately 87% of the data belongs
      to this distribution. We also derived a method to investigate the effect of both
      the correlation and selection cut-off on the relative power of pooling studies.
      We demonstrate that pooled genotyping has good power to detect SNPs that are
      truly associated with disease-causing variants for SNPs showing good correlation
      between pooled and individual genotyping. Therefore, this approach is a cost
      effective tool for association studies.

PMID- 19172082
TI  - A model for fine mapping in family based association studies.
AB  - Genome wide association studies for complex diseases are typically followed by
      more focused characterization of the identified genetic region. We propose a
      latent class model to evaluate a candidate region with several measured markers
      using observations on families. The main goal is to estimate linkage
      disequilibrium (LD) between the observed markers and the putative true but
      unobserved disease locus in the region. Based on this model, we estimate the
      joint distribution of alleles at the observed markers and the unobserved true
      disease locus, and a penetrance parameter measuring the impact of the disease
      allele on disease risk. A family specific random effect allows for varying
      baseline disease prevalences for different families. We present a likelihood
      framework for our model and assess its properties in simulations. We apply the
      model to an Alzheimer data set and confirm previous findings in the ApoE region.

PMID- 19172083
TI  - Variance components linkage analysis with repeated measurements.
AB  - BACKGROUND: When subjects are measured multiple times, linkage analysis needs to
      appropriately model these repeated measures. A number of methods have been
      proposed to model repeated measures in linkage analysis. Here, we focus on
      assessing the impact of repeated measures on the power and cost of a linkage
      study. METHODS: We describe three alternative extensions of the variance
      components approach to accommodate repeated measures in a quantitative trait
      linkage study. We explicitly relate power and cost through the number of measures
      for different designs. Based on these models, we derive general formulas for
      optimal number of repeated measures for a given power or cost and use analytical
      calculations and simulations to compare power for different numbers of repeated
      measures across several scenarios. We give rigorous proof for the results under
      the balanced design. RESULTS: Repeated measures substantially improve power and
      the proportional increase in LOD score depends mostly on measurement error and
      total heritability but not much on marker map, the number of alleles per marker
      or family structure. When measurement error takes up 20% of the trait variability
      and 4 measures/subject are taken, the proportional increase in LOD score ranges
      from 38% for traits with heritability of approximately 20% to 63% for traits with
      heritability of approximately 80%. An R package is provided to determine optimal
      number of repeated measures for given measurement error and cost. Variance
      component and regression based implementations of our methods are included in the
      MERLIN package to facilitate their use in practical studies.

PMID- 19172085
TI  - Ranking bias in association studies.
AB  - BACKGROUND: It is widely appreciated that genomewide association studies often
      yield overestimates of the association of a marker with disease when attention
      focuses upon the marker showing the strongest relationship. For example, in a
      case-control setting the largest (in absolute value) estimated odds ratio has
      been found to typically overstate the association as measured in a second,
      independent set of data. The most common reason given for this observation is
      that the choice of the most extreme test statistic is often conditional upon
      first observing a significant p value associated with the marker. A second, less
      appreciated reason is described here. Under common circumstances it is the
      multiple testing of many markers and subsequent focus upon those with most
      extreme test statistics (i.e. highly ranked results) that leads to bias in the
      estimated effect sizes. CONCLUSIONS: This bias, termed ranking bias, is separate
      from that arising from conditioning on a significant p value and may often be a
      more important factor in generating bias. An analytic description of this bias,
      simulations demonstrating its extent, and identification of some factors leading
      to its exacerbation are presented.

PMID- 19172086
TI  - Case-deletion diagnostics for maximum likelihood multipoint quantitative trait
      locus linkage analysis.
AB  - OBJECTIVES: Case-deletion diagnostic methods are tools that allow identification
      of influential observations that may affect parameter estimates and model fitting
      conclusions. The goal of this paper was to develop two case-deletion diagnostics,
      the exact case deletion (ECD) and the empirical influence function (EIF), for
      detecting outliers that can affect results of sib-pair maximum likelihood
      quantitative trait locus (QTL) linkage analysis. METHODS: Subroutines to compute
      the ECD and EIF were incorporated into the maximum likelihood QTL variance
      estimation components of the linkage analysis program MAPMAKER/SIBS. Performance
      of the diagnostics was compared in simulation studies that evaluated the
      proportion of outliers correctly identified (sensitivity), and the proportion of
      non-outliers correctly identified (specificity). RESULTS: Simulations involving
      nuclear family data sets with one outlier showed EIF sensitivities approximated
      ECD sensitivities well for outlier-affected parameters. Sensitivities were high,
      indicating the outlier was identified a high proportion of the time. Simulations
      also showed the enormous computational time advantage of the EIF. Diagnostics
      applied to body mass index in nuclear families detected observations influential
      on the lod score and model parameter estimates. CONCLUSIONS: The EIF is a
      practical diagnostic tool that has the advantages of high sensitivity and quick
      computation.

PMID- 19172084
TI  - Haplotyping methods for pedigrees.
AB  - Haplotypes provide valuable information in the study of diseases, complex traits,
      population histories, and evolutionary genetics. With the dramatic increase in
      the number of available single nucleotide polymorphism (SNP) markers, haplotype
      inference (haplotyping) using observed genotype data has become an important
      component of genetic studies in general and of statistical gene mapping in
      particular. Existing haplotyping methods include (1) population-based methods,
      (2) methods for pooled DNA samples, and (3) methods for family and pedigree data.
      The methods and computer programs for population data and pooled DNA samples were
      reviewed recently in the literature. As several authors noted, family and
      pedigree datasets are abundant and have unique advantages. In the past twenty
      years, many haplotyping methods for family and pedigree data have been developed.
      Therefore, in this contribution we review haplotyping methods and the
      corresponding computer programs suitable for family and pedigree data and discuss
      their applications and limitations. We explore the connections among these
      methods, and describe the challenges that remain to be addressed.

PMID- 19172087
TI  - When a case is not a case: effects of phenotype misclassification on power and
      sample size requirements for the transmission disequilibrium test with affected
      child trios.
AB  - Phenotype misclassification in genetic studies can decrease the power to detect
      association between a disease locus and a marker locus. To date, studies of
      misclassification have focused primarily on case-control designs. The purpose of
      this work is to quantify the effects of phenotype misclassification on the
      transmission disequilibrium test (TDT) applied to affected child trios, where
      both parents are genotyped. We compute the non-centrality parameter of the
      distribution corresponding to the TDT statistic when there is linkage and
      association of a marker locus with a disease locus and there is phenotype
      misclassification. We verify our analytic calculations with simulations and
      provide an example sample size calculation. In our simulation studies, the
      maximum absolute difference between statistical power computed by simulation and
      analytic methods is 0.018. In an example sample size calculation, we observe that
      to maintain equivalent power, the required sample size increases when the disease
      prevalence decreases or when the misclassification rate increases. A 39-fold
      sample size increase is required when the misclassification rate is 5% and the
      disease prevalence is 1%. Given the potentially substantial power loss for the
      TDT in the presence of misclassification, we recommend that researchers
      incorporate phenotype misclassification into their study design for genetic
      association using trio data. We have developed freely available software that
      computes power loss for a fixed sample size or sample size for a fixed power in
      the presence of phenotype misclassification.

PMID- 19172088
TI  - Chemotherapy in patients with penile carcinoma.
AB  - The prognosis of patients with advanced penile carcinoma is poor. There are only
      few studies, mostly with a low number of patients, which show a low response rate
      with severe toxicity. While adjuvant and palliative chemotherapy for penile
      cancer is universally characterized by low efficacy, neoadjuvant approaches for
      patients with fixed lymph node metastases have shown some response. Overall,
      recent experiences with new chemotherapeutic approaches (i.e. taxane-based
      combinations) have shown some encouraging results. Therefore, these combinations
      should be investigated in larger and multi-center studies.

PMID- 19172089
TI  - Bicycle saddle pressure: effects of trunk position and saddle design on healthy
      subjects.
AB  - OBJECTIVE: There is a common belief that seat pressure during cycling can
      compress specific neurovascular tissues over the perineum leading to genital
      pathologies. This topic has seldom been discussed for women. The present study
      was conducted to verify the effect of trunk position and saddle design on saddle
      pressure in both men and women. METHODS: Recreational cyclists (11 men and 11
      women) were evaluated while seated on a bicycle. Saddle pressure was measured
      with F-scan insoles adapted for two saddle models (with and without a hole), and
      two trunk positions (upright and forwards). Pressure values were compared between
      trunk positions and saddles employing ANOVA. RESULTS: There were no statistical
      differences comparing saddle pressure between the two trunk positions for women.
      For men a statistical difference between the trunk positions for the saddle with
      a hole was found. Thus, the trunk forwards shift seems to affect the values of
      saddle pressure only for men using the 'holed' saddle. CONCLUSION: Saddle
      pressure for men was influenced by saddle design and trunk position only. This
      result indicates that the masculine anatomy may influence saddle pressure during
      bicycle.

PMID- 19172090
TI  - Transrectal ultrasound as diagnostic tool for the detection of local recurrence
      following cystectomy and urinary diversion.
AB  - OBJECTIVE: Routine follow-up after cystectomy for bladder cancer detect patients
      with local recurrence late in the course of disease. We set out to determine the
      value of transrectal ultrasound (TRUS) as diagnostic tool to diagnose local
      failure. PATIENTS AND METHODS: Between 1986 and 2003, radical cystectomy for
      bladder cancer with orthotopic diversion was performed in 642 male patients. We
      identified all patients that simultaneously had transabdominal ultrasound,
      digital rectal examination, TRUS and CT/MRI of the pelvis at the diagnosis of
      local recurrence. RESULTS: Mean follow-up was 59.4 months. 83/642 patients (13%)
      had local failure of bladder cancer during follow-up. In 48/642 patients (7.5%)
      the local recurrence was the first site of recurrence. 35/642 patients (5.5%)
      developed local failure with concomitant distant disease. 31/83 patients met the
      inclusion criteria. The median time between cystectomy and diagnosis of local
      recurrence was 13 months (2-51 months). Routine follow-up detected local
      recurrence in 1 asymptomatic patient. 25/31, 3/31 and 2/31 patients had pain in
      the lower extremities/pelvis, hematuria and urinary retention, respectively.
      Digital rectal examination, transabdominal ultrasound, TRUS, and CT/MRI of the
      pelvis were suspicious for local recurrence in 9, 7, 26, and 29 patients,
      respectively. CONCLUSIONS: TRUS is a highly sensitive tool in detecting local
      recurrence following cystectomy. It is easy to perform and inexpensive. We
      recommend TRUS in short intervals in all patients with high risk for local
      recurrence in order to detect cancer early.

PMID- 19172091
TI  - Health-related quality of life after radical prostatectomy and low-dose-rate
      brachytherapy for localized prostate cancer.
AB  - OBJECTIVE: To evaluate quality of life (QOL) after radical retropubic
      prostatectomy (RP) and low-dose-rate brachytherapy (BT). METHODS: Between 2001
      and 2004, RP or BT was performed in 212 patients. QOL data were evaluated with
      the European Organization for Research and Treatment of Cancer QLQ-C30 version
      3.0, the International Prostate Symptom Score (IPSS) and the International Index
      of Erectile Function-5 questionnaires. QOL data were compared. RESULTS: RP and BT
      were performed in 142 and 70 patients, respectively. The mean follow-up was 24
      months (5-53). The mean overall global health score for patients after RP was 78
      (0-100) and after BT it was 83 (33-100), and it showed a trend in favour of BT.
      The follow-up lasted at most 53 months, and the period was divided into yearly
      categories. Patients who underwent BT showed worse global health in the first
      year after operation, but thereafter they showed better health. Patients who
      received BT showed a trend towards having lower functional-scale and symptom
      scale scores in the first year after operation, and then higher scores for any
      subsequent year of follow-up. Only diarrhoea was temporarily worse in the second
      year after BT compared to RP. The mean total IPSS and QOL score for BT and RP
      patients during follow-up showed no significant difference. CONCLUSION: Patients
      treated with BT or RP have similar QOL scores. QOL after BT is worse in the first
      year after treatment, but thereafter it is better than QOL after RP.

PMID- 19172092
TI  - Nephron-sparing surgery: the effect of surface cooling and temporary renal artery
      occlusion on renal function.
AB  - AIMS: To evaluate whether transient renal artery clamping and external renal
      hypothermia cause any detrimental effect on the remaining renal parenchyma after
      nephron-sparing surgery with the use of (99m)Tc-DMSA-SPECT. METHODS: Twenty-eight
      patients with a unilateral renal mass but a normal contralateral kidney underwent
      nephron-sparing surgery. Serum biochemistry, 24-hour urinary creatinine clearance
      and absolute uptakes of the injected dose (%ID) of both kidneys as measured by
      renal (99m)Tc-DMSA-SPECT were compared preoperatively and in the 3rd
      postoperative month. (99m)Tc-DMSA uptakes in the contralateral kidney were used
      as controls. RESULTS: The average tumor size and mean renal artery clamping time
      were 37.4 +/- 11.3 (range 25-68) mm and 53.7 +/- 13 (range 38-90) min,
      respectively. Pre- and postoperative mean absolute uptakes of %ID in the
      remaining parenchyma of the operated kidneys were 15.13 +/- 3.30 and 14.74 +/-
      3.38%, respectively (p = 0.052). In the contralateral kidneys, there was also no
      significant difference between the two studies (18.82 +/- 6.26 vs. 19.14 +/-
      7.19%, respectively; p = 0.546). Likewise, there was no statistically significant
      difference between pre- and postoperative serum creatinine (p = 0.179) and
      creatinine clearance values (p = 0.108). CONCLUSION: Renal artery clamping and
      external cooling during nephron-sparing surgery have no demonstrable harmful
      effects on the renal parenchyma as measured by (99m)Tc-DMSA-SPECT analysis.

PMID- 19172093
TI  - Our 21-year experience with the Thiersch-Duplay technique following surgical
      correction of penoscrotal transposition.
AB  - OBJECTIVES: To assess surgical techniques applied after surgical correction of
      penoscrotal transposition and their complications. METHODS: The medical records
      of 64 patients with a mean age of 4.1 years (range 1-24) who underwent surgical
      correction for penoscrotal transposition and subsequent Thiersch-Duplay
      urethroplasty in the last 21 years were evaluated retrospectively. RESULTS: All
      cases underwent Thiersch-Duplay urethroplasty following reconstruction of
      penoscrotal transposition after a minimum interval of 6 months. Following
      Thiersch urethroplasty, 41 (64%) cases with successful outcomes had glandular
      meatuses. Of the remaining 23 (36%) patients 15, 7 and 1 patients underwent
      second operations for urethrocutaneous fistulas, meatal regressions and urethral
      diverticulum, respectively. Eleven of 15 patients underwent primary fistula
      repair and 4 patients, turnover fistula repair. These patients had glandular
      meatuses following fistula repair. Seven cases with meatal regression and
      breakdown of the neourethra were reoperated on by using double-face
      urethroplasty, onlay island flap urethroplasty and free-tube urethroplasty
      techniques. Finally, all patients had glandular meatuses. One patient with
      urethral diverticulum underwent successful diverticulum excision and meatoplasty.
      CONCLUSIONS: Thierch urethroplasty is the most commonly performed technique after
      surgical correction of penoscrotal transposition; however, additional procedures
      are needed for the management of its complications.

PMID- 19172094
TI  - Prostatitis-like symptoms: diagnosis and management in a Malaysian primary care
      population.
AB  - BACKGROUND: Little is known about how primary care physicians (PCPs) in Asia
      diagnose and manage prostatitis-like symptoms. This study investigated the
      clinical diagnosis of and care provided for prostatitis-like symptoms by PCPs in
      a Malaysian population, and compared these findings to reports from other areas.
      METHODS: All members of the Penang Private Medical Practitioners' Society were
      asked to complete a self-administered survey. Nonresponders were contacted after
      3 weeks and received a telephone request after 6 weeks. RESULTS: Of the 786
      practitioners contacted, 669 considered themselves to be PCPs, including 279
      (42%) who responded to the survey. Adult males with prostatitis-like symptoms
      typically constitute <1% of the patients seen by PCPs. Most PCPs (72%) believe
      that prostatitis-like symptoms are caused by bacterial infection. 61% of PCPs
      base their diagnosis of prostatitis-like symptoms on clinical history, a physical
      examination and dipstick urinalysis. Standard management was to prescribe 1 or 2
      courses of antimicrobials. CONCLUSIONS: Despite the 8.7% prevalence found in a
      previous survey in this population, prostatitis remains underdiagnosed in
      Malaysia. In contrast to many other clinical settings, urologists in Malaysia see
      a large proportion of newly diagnosed and treatment-naive prostatitis patients,
      providing an opportunity for clinical diagnostic and treatment studies.

PMID- 19172095
TI  - Hydronephrosis promotes expression of hypoxia-inducible factor 1 alpha.
AB  - BACKGROUND: Obstructive uropathy is argued to involve an ischemia-type tissue
      injury. Further, hypoxia-inducible factor 1 alpha (HIF-1 alpha) constitutes a
      nuclear transcription factor normally upregulated under hypoxic conditions. We
      hypothesized that HIF-1 alpha is expressed in the hydronephrotic renal pelvis, as
      a result of tissue hypoxia. PATIENTS AND METHODS: Renal pelvis tissue specimens
      were obtained from 2 patient groups. Group 1 (controls, n = 10) consisted of
      patients who underwent nephrectomy due to nonobstructive renal malignancy. Group
      2 (n = 18) consisted of patients who underwent open procedures due to intractable
      hydronephrosis, not amenable to conservative measures. HIF-1 alpha detection was
      conducted via immunohistochemical techniques, while histological alterations in
      both groups were also recorded. RESULTS: Smooth muscle hypertrophy and urothelial
      hyperplasia were major findings in group 2. HIF-1 alpha-positive cells
      (fibroblasts and occasionally macrophages), mainly localized in the stroma, were
      also found to a greater extent in group 2 (p = 0.0066). CONCLUSION: We conclude
      that HIF-1 alpha is mainly expressed in stroma fibroblasts of the hydronephrotic
      renal pelvis, implying the presence of significant tissue hypoxia at the dilated
      upper urinary tract.

PMID- 19172096
TI  - Alterations of urine TGF-beta1 and bFGF following bladder outlet obstruction: a
      predictor for detrusor contractibility?
AB  - OBJECTIVES: To investigate the alterations of urine transforming growth factor
      beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) following bladder
      outlet obstruction (BOO) in rats and to determine their correlation with the
      impaired detrusor contractibility. METHODS: Wistar rats were divided into
      control, 2-week BOO 6-week and BOO groups. Impaired detrusor contractibility was
      quantified by measuring detrusor contraction force (DCF) of detrusor strip
      stimulated by carbachol. The enzyme-linked immunosorbent assay method was used to
      determine the urine levels of the 2 factors. Correlation analysis was conducted
      between DCF and urine levels of the 2 factors to see if there was an association
      between them after BOO. RESULTS: DCF was found to be significantly lower in the 6
      week BOO group than in the 2-week BOO and control groups. There is no significant
      difference regarding urine TGF-beta1 between the 2-week BOO and control groups (p
      > 0.05). Urine TGF-beta1 level in the 6-week BOO group was significantly higher
      than in the 2-week BOO (p < 0.05) and control groups (p < 0.05). There existed a
      negative correlation between DCF and urine TGF-beta1 (p < 0.05). CONCLUSIONS: In
      an animal model, our results have suggested the potential role of urine TGF-beta1
      as a noninvasive biomarker to predict detrusor contractibility after BOO.

PMID- 19172097
TI  - Local factors compared with systemic factors in the formation of bladder uric
      acid stones.
AB  - AIM: The aim of this study was to evaluate the clinical characteristics of uric
      acid urolithiasis and how the presentation differs between urolithiasis of the
      upper urinary tract (UUT) compared with urolithiasis of the bladder. We attempted
      to evaluate the importance of local vs. systemic factors in the formation of
      bladder uric acid stones. PATIENTS AND METHODS: The medical records of 77
      consecutive patients with uric acid urolithiasis from January 2004 to December
      2006 were reviewed retrospectively. In all patients, histories were recorded, and
      physical examinations, renal function tests and urine analysis were done. The
      features of the treated stones were recorded, and the chemical composition was
      analyzed by computed Fourier transform infrared spectrophotometry. RESULTS: Among
      77 patients with uric acid stones, 66 were male and 11 were female (ratio of
      7.6:1). Mean age was 59.50 +/- 10.46 years. Of the stones, 55 (71.4%) were
      located in the UUT (UUT group) and 22 (28.6%) in the bladder (bladder group).
      Multiple presentations of urolithiasis at diagnosis were found in 56 (72.7%)
      patients. The mean values of serum creatinine and uric acid were 148.28 +/- 70.69
      and 443.33 +/- 95.91 micromol/l, respectively. Mean body mass index (BMI) was
      26.78 +/- 2.90, and 72.7% of patients were overweight or obese. Mean urinary pH
      was 5.39. No significant differences existed between the 2 groups in regard to
      gender, BMI, urinary pH, stone nature, or presence of hypertension, gout, and/or
      urinary tract infections. In the bladder group, the incidence of benign prostate
      hyperplasia was significantly increased, and the incidence of diabetes mellitus
      was significantly lower, as were levels of serum uric acid and creatinine.
      CONCLUSIONS: Uric acid urolithiasis was predominant in men in this study. These
      patients tended to be obese or overweight, with multiple stone presentations and
      low urinary pH. Furthermore, the bladder uric acid stone group had significantly
      lower levels of serum creatinine and uric acid, and lower percentages of diabetes
      mellitus but higher incidences of benign prostate hyperplasia in comparison with
      the UUT group. The local factor seems more important than the systemic factor in
      the formation of bladder uric acid stone.

PMID- 19172098
TI  - Statistical evaluation of hemodynamic effects of regular use of sildenafil on the
      human corpora cavernosa.
AB  - INTRODUCTION: Sildenafil citrate is currently used on demand in the treatment of
      erectile failure, regardless of etiology. Nevertheless, recent data suggest a
      significant improvement in nocturnal penile erections in potent and impotent men
      taking a single dose at bedtime. The present study analyzes whether continuous
      use of sildenafil positively correlates with improvement of penile blood flow and
      treatment satisfaction referred by patients with erectile dysfunction (ED) of
      vascular origin. PATIENTS AND METHODS: A total of 32 patients, mean age 54, with
      ED of vascular etiology, were evaluated at the beginning and at the end of our
      study using the International Index of Erectile Function (IIEF-5) and pharmaco
      penile duplex ultrasonography during basic and dynamic phases. These patients
      were treated with sildenafil (50 mg) twice a week for 4 months. During pharmaco
      penile duplex ultrasonography, we measured basal peak flow velocity, basal
      acceleration of peak flow in both cavernous arteries before intracavernous (i.c.)
      pharmaco-stimulation, maximum peak flow velocities and end-diastolic flow
      velocities after i.c. stimulation. The data observed were compared with those of
      10 patients with ED who voluntarily decided not to take any treatment. RESULTS
      AND CONCLUSIONS: In this study, basal peak flow velocity, basal acceleration,
      maximum peak flow velocity and IIEF-5 scores were found to significantly increase
      after treatment. All differences were statistically significant (p < 0.05). Only
      few mild adverse effects were observed. Our data suggest that the regular use of
      sildenafil (50 mg) improves the blood flow in cavernous arteries increasing
      sexual performance in patients with ED of vascular origin.

PMID- 19172099
TI  - Transurethral incision of the bladder neck using KTP in the treatment of bladder
      neck obstruction in women.
AB  - OBJECTIVES: To study the results and complications of the potassium-titanyl
      phosphate (KTP, green) laser during transurethral incision of the bladder neck in
      the treatment of female voiding dysfunction due to bladder neck obstruction.
      METHODS: A total of 40 women (43-79 years of age) with obstruction were
      identified. Patients with neurogenic, traumatic, or iatrogenic causes of
      obstruction were excluded. Preoperative investigations included a full urodynamic
      examination and urethrocystoscopy. Transurethral bladder neck incision with KTP
      was performed in all patients. Urodynamic results, clinical improvements in
      voiding symptoms, and volume of bleeding were assessed. RESULTS: Of the 40
      patients, 12 had chronic urinary retention and 28 had difficult micturition. The
      most common findings on urodynamic study were a high voiding pressure plus low
      flow rate and high urethral pressure. After treatment, the lower urinary tract
      symptoms were resolved or improved in all patients. Urodynamic study revealed
      decreased voiding pressure, post-void residual urine volume, and increased
      maximal flow rate. CONCLUSIONS: Transurethral incision of the bladder neck is
      effective in relieving voiding difficulties owing to anatomic or functional
      bladder neck obstruction in women. KTP has great efficacy in the treatment of
      female voiding dysfunction due to bladder neck obstruction.

PMID- 19172100
TI  - Cystic nephroma, cystic partially differentiated nephroblastoma and cystic Wilms'
      tumor in children: a spectrum with therapeutic dilemmas.
AB  - BACKGROUND: Cystic renal tumors are a diagnostic and therapeutic challenge.
      Cystic nephroma (CN), cystic partially differentiated nephroblastoma (CPDN) and
      cystic Wilms' tumor (CWT) are a spectrum with CN at the benign end, CWT at the
      malignant end and CPDN in the intermediate position. CN and stage 1 CPDN are
      often treated with surgery alone. International Society of Pediatric Oncology
      (SIOP) protocols for Wilms' tumor (WT) advocate preoperative chemotherapy, which
      may be unnecessary and potentially harmful in CN and in stage 1 CPDN. There are
      difficulties in differentiating the three types using imaging techniques.
      Therefore, controversies exist regarding the optimal treatment. METHODS: We
      describe 6 children, who each had a postoperative diagnosis of CN, CPDN or CWT,
      and we retrospectively evaluate the treatment strategies. RESULTS: The three
      types cannot be differentiated using imaging techniques, although the presence of
      solid components in the tumor is indicative of WT. CONCLUSIONS: Surgery as first
      line therapy should be seriously considered in children who have a cystic renal
      tumor, but further collaborative studies are needed since the distinction line
      between CPDN and CWT is not always clear.

PMID- 19172101
TI  - Uroflow findings in older boys with tubularized incised-plate urethroplasty.
AB  - AIM: To analyze uroflow findings in older boys with tubularized incised-plate
      urethroplasty (TIPU). MATERIALS AND METHODS: 79 toilet-trained patients who had
      TIPU were evaluated by studying their voiding history, a physical examination,
      suprapubic ultrasound and uroflowmetry, both pre- and postoperatively. The
      obstructive urinary flow pattern (OUFP) was accepted as low maximum urinary flow
      rate with plateau, staccato or intermittent shape. RESULTS: The mean age was 7
      years (range 5-11). The mean follow-up was 30 months (range 6-36). Of the 79
      patients, 70 recovered. A permanent OUFP was found in 10 of 63 patients, as
      follows: 7 were detected in the 6th month after operation, and 1 each in the 9th,
      18th and 36th months.Ten patients had no voiding abnormality and significant
      residual urine. The mean interval from initial surgery to presentation with an
      OUFP was 10.5 months. CONCLUSIONS: An occult urethral obstruction develops in
      some asymptomatic children with TIPU and commonly occurres in the first year
      after operation.

PMID- 19172102
TI  - Influence of high bladder pressure on vesicoureteral reflux and its resolution.
AB  - OBJECTIVES: Voiding dysfunction may result in lower urinary tract symptoms in
      children and is associated with urinary tract infection, renal damage and
      vesicoureteral reflux (VUR). The aim of this study was to assess the relationship
      between detrusor pressure, VUR and abnormal renal scintigraphy findings in
      children with dysfunctional voiding. PATIENTS AND METHODS: Between 2004 and 2007,
      30 children with VUR and voiding dysfunction, 22 girls and 8 boys, median age 8.2
      years, were evaluated. Urodynamic study, renal scan and voiding
      cystourethrography were performed in all patients. RESULTS: The degree of the
      renal scarring was found to be associated with the detrusor pressures (p =
      0.018). The highest detrusor pressure was shown in the group of urge syndrome.
      The degree of the VUR was found to be correlated with the detrusor pressures (p =
      0.038). In our study group, VUR had resolved in 11 (37%) patients, had improved
      in grade in 10 (33%) patients and remained unchanged in 9 (30%) patients after
      anticholinergic therapy. No significant relationship was found between the
      duration of therapy and the voiding patterns (p = 0.389). CONCLUSION: Every child
      with VUR should undergo a careful evaluation of its bladder function. The
      patients who have high detrusor pressures should be evaluated carefully for the
      presence of VUR and renal damage.

PMID- 19172103
TI  - Long-term efficiency of skin stretching and a topical corticoid cream application
      for unretractable foreskin and phimosis in prepubertal boys.
AB  - OBJECTIVES: To evaluate the long-term efficacy of topical application of a potent
      corticoid cream and skin stretching in the treatment of unretractable foreskin,
      pinpoint phimosis, balanopreputial adhesions and lichen sclerosus in prepubertal
      boys. METHODS: 462 prepubertal boys (mean age 4.7 years) with unretractable
      foreskin applied a topical potent corticoid cream together with skin stretching
      twice daily for 6 weeks. Follow-up interview of all patients was performed to
      evaluate long-term results (median 22 months). Short- and long-term results were
      compared and evaluated. RESULTS: 400/462 boys (86%) had a retractable prepuce
      after 6 weeks of treatment. 62/462 boys had no or only a partial response. After
      a median follow-up of 22 months, the treatment continued to be successful in
      383/462 boys (83%). In 76/462 boys the foreskin was unretractable, of which 35
      preferred surgical treatment. 12/462 boys presented with lichen sclerosus and the
      non-surgical treatment appeared efficient in 9/12 (67%). CONCLUSIONS: This study
      has shown that local application of a potent corticoid cream and skin stretching
      is a safe, simple and effective long-term treatment for all types of
      unretractable foreskin in prepubertal boys. The efficiency of the treatment was
      not related to the age of the patient or the type of unretractable foreskin.

PMID- 19172104
TI  - Development of Sertoli cells during mini-puberty in normal and cryptorchid
      testes.
AB  - BACKGROUND: Only a few studies have dealt with quantitative changes of Sertoli
      cells during human development, and the results of these studies are conflicting.
      Our hypothesis is that the development of Sertoli cells during mini-puberty
      follows the same pattern as germ cells. METHODS: We examined the biopsies of
      cryptorchid and normal testes from patients aged 1-12 months. Fifty complete,
      rounded tubules were examined and the number of Sertoli cells per tubule was
      determined. We compared the numbers in cryptorchid and normal testes, as well as
      the average number of Sertoli cells in each age group separately. RESULTS: The
      number of Sertoli cells per tubule in the cryptorchid testes of patients aged 1-4
      months was 22.38 +/- 1.01 compared to cryptorchid patients aged 5-12 months
      (23.20 +/- 1.41). This number in patients with spontaneously descended testes
      aged 1-4 months was 23.53 +/- 1.98, while this number in the same group of
      patients aged 5-12 months was 26.20 +/- 1.40. The difference between the two age
      groups was statistically significant (p < 0.001, two-tailed test). CONCLUSIONS:
      Our results suggest the number of Sertoli cells increases with the hormonal
      surge. In cryptorchid patients, the number of Sertoli cells is diminished
      compared to the normal testis.

PMID- 19172105
TI  - Low transscrotal orchidopexy is a safe and effective approach for undescended
      testes distal to the external inguinal ring.
AB  - OBJECTIVES: To review the results of a low transscrotal orchidopexy in patients
      with palpable undescended testes located distal to the external inguinal ring.
      METHODS: Between July 1998 and June 2005, transscrotal orchidopexy with a single
      low scrotal incision was performed in 32 patients for 49 undescended testes. The
      indication was an undescended testis that lay distal to the external ring and
      could be pulled down manually into the scrotum under general anesthesia. RESULTS:
      All testes that were treated with the low transscrotal approach were successfully
      fixed in the middle or lower portion of the scrotum. The mean operative time was
      significantly shorter for the low transscrotal orchidopexy (45.2 min) than for
      the inguinal orchidopexy (66.6 min) for 107 undescended testes at similar
      locations. The median follow-up duration was 39.1 months; all testes except 1
      (97.7%) were located in a good position within the scrotum and had a good
      consistency; 1 testis ascended postoperatively and required inguinal orchidopexy.
      No inguinal hernias or hydroceles occurred after the surgery. CONCLUSIONS: Low
      transscrotal orchidopexy appears to be an excellent alternative to the standard
      inguinal orchidopexy for undescended testes located distal to the external
      inguinal ring.

PMID- 19172106
TI  - Properties in penetrating capsula of transurethral plasmakinetic resection:
      comparison with transurethral resection of the prostate in an ex vivo study.
AB  - AIM: As capsular perforation is still regarded as one of complications of
      transurethral prostatectomy, the aim of this study was to compare the properties
      in penetrating capsular tissue of transurethral plasmakinetic resection (PKRP)
      and transurethral resection of the prostate (TURP). METHODS: Isolated normal
      saline-perfused porcine kidneys were used to determine the penetrating capsule
      properties of PKRP and TURP. We quantified and compared the time of cutting
      through renal surface during different procedures. RESULTS: The time of
      perforating renal capsula induced by PKRP was longer than that by TURP (p <
      0.05). As soon as the operator activated footswitch, the renal capsula was cut
      through by the monopolar loop. The duration was always less than 1 s in the TURP
      group, although sometimes the plasma-loop could not penetrate the velamen
      (15/40). The time of penetrating the renal surface with capsula induced by PKRP
      was longer than that without capsula (p < 0.05). The duration of penetrating the
      surface without capsula was always less than 1 s. CONCLUSIONS: With the present
      ex vivo model, we provided evidence that it is more difficult to penetrate
      capsular tissue with PKRP compared to TURP.

PMID- 19172107
TI  - In vitro and in vivo effects of vardenafil (a PDE-5 Inhibitor) on corpus
      cavernosal smooth muscle relaxation in diabetic rabbits.
AB  - INTRODUCTION: Diabetes mellitus is associated with impaired cavernosal smooth
      muscle relaxation (CSMR) and the development of erectile dysfunction (ED).
      Vardenafil, a phosphodiesterase type 5 inhibitor has been used to treat ED. The
      aim of this study was to assess the in vitro and in vivo effects of vardenafil on
      diabetic rabbit CSMR. METHODS: Organ bath studies were used. RESULTS: Sodium
      nitroprusside (SNP)- and electrical field stimulation (EFS)-induced CSMR in
      diabetic rabbits given the vehicle was significantly impaired when compared with
      controls. The in vitro addition of vardenafil significantly enhanced SNP-induced
      CSMR in diabetic animals given the vehicle. SNP-induced CSMR in diabetic animals
      given in vivo vardenafil was significantly increased when compared with the
      diabetic untreated group. The in vitro addition of vardenafil significantly
      enhanced SNP and EFS-induced CSMR in cavernosal tissue taken from diabetic
      animals given vardenafil in vivo. CONCLUSIONS: The present findings suggest that
      the combination of in vitro and in vivo vardenafil enhance diabetic CSMR,
      reinforcing the use of vardenafil for the treatment of diabetes-induced ED.

PMID- 19172108
TI  - Study of 5-Aza-CdR on transcription regulation of RASSF1A gene in the BIU87 cell
      line.
AB  - OBJECTIVES: To investigate the effect of 5-Aza-CdR on methylation and expression
      of RASSF1A gene in the human bladder cancer BIU87 cell line. METHODS: Cultured
      BIU87 cells were treated with increasing concentrations (0.1, 0.5, 1.0, 5.0
      micromol/l) of 5-Aza-CdR. MTT was used to detect the proliferation of BIU87
      cells. The methylation status and expression level of RASSF1A gene in BIU87 cells
      were analyzed by methylation-specific polymerase chain reaction and RT-PCR before
      and after treatment with 5-Aza-CdR. Meanwhile, Western blot was used to detect
      the changes of RASSF1A protein. RESULTS: In this study we found that the growth
      velocity of the BIU87 cell line was suppressed to various degrees after having
      been treated with different concentrations of 5-Aza-CdR, and the survival rate
      decreased with increasing 5- Aza-CdR concentrations. Besides, the methylation
      status of RASSF1A was obviously reversed and mRNA was re-expressed after
      treatment with 5-Aza-CdR. Expression of RASSF1A protein increased with increasing
      5-Aza-CdR concentrations. CONCLUSIONS: Our results suggest that the tumor
      suppressive effect of 5-Aza-CdR may result from reactivation of silenced RASSF1A
      through a demethylation function.

PMID- 19172109
TI  - Prostate cancer-producing granulocyte colony-stimulating factor.
AB  - An 86-year-old man with a serum prostate-specific antigen level of 93.33 ng/ml
      was diagnosed as having cT3aN0M0 prostatic adenocarcinoma of Gleason score 9.
      Although the serum prostate-specific antigen responded well to combined androgen
      blockade, the cancer spread and lead to death 6 months after diagnosis. The
      patient had leukocytosis during the clinical course with no sign of localized
      infection, especially after manipulation of the prostate. Enzyme immunoassay
      demonstrated elevated serum levels of granulocyte colony-stimulating factor (G
      CSF) and macrophage colony-stimulating factor. To our knowledge, this is the
      first case of prostate cancer with G-CSF production, which was confirmed
      immunohistochemically.

PMID- 19172110
TI  - Collagen graft interposition in vesicovaginal fistula treatment.
AB  - Vesicovaginal fistula (VVF) is a quite rare complication of gynecological
      surgery. The first attempt to repair the fistulous tract offers the best
      opportunity for cure. We report the successful repair of VVF in 2 patients using
      a combined anterior vaginal approach and porcine dermal collagen grafting as
      interposition tissue. Favorable results confirm technical simplicity, safety and
      efficacy of this procedure.

PMID- 19172111
TI  - A new modified renal vein anastomosis in unilateral dual renal transplantation.
AB  - Transplantation of renal allografts inadequate to meet the recipient's metabolic
      needs has been proposed as a cause of chronic allograft failure. Dual renal
      transplant is a novel idea to transplant enough nephron mass to solve this
      problem. According to the current literature, graft renal veins are anastomosed
      to the external iliac vein or inferior vena cava as venous drainage in the
      setting of dual renal transplantation. In the presented case, renal blood was
      returned through one of the grafts back to the systematic circulation through the
      other renal vein graft. This provides a feasible option for unilateral dual renal
      transplantation to accomplish renal vein anastomosis in some difficult
      situations.

PMID- 19172112
TI  - Mucoepidermoid lung tumor appearing as an abscess on the scrotum.
AB  - The authors present the case of a 52-year-old man who had recurring scrotal
      abscesses resulting in oncotomy being carried out seven times within 2 years.
      Eventually, it was dissected out totally. Histology proved anaplastic cancer
      metastasis. The primary tumor was detected in the bronchia; moreover, metastases
      were found in other organs as well. The patient died 6 weeks after the first
      diagnosis. We intended to draw attention to frequently occurring scrotal
      inflammation and thus the underlying diseases. We emphasize the importance of
      histology examinations.

PMID- 19172113
TI  - Aggregation of expanded huntingtin in the brains of patients with Huntington
      disease.
AB  - Huntingtin containing an expanded polyglutamine causes neuronal death and
      Huntington disease. Although expanded huntingtin is found in virtually every cell
      type, its toxicity is limited to neurons of certain areas of the brain, such as
      cortex and caudate/putamen. In affected areas of the brain, expanded huntingtin
      is not found in its intact monomeric form. It is found instead in the form of N
      terminal fragments, oligomers and polymers, all of which accumulate in the
      cortex. Whereas the oligomer is mostly soluble, the polymers and the fragments
      associate with each other and with other proteins to form the insoluble
      inclusions characteristic of the disease. It is likely that the aggregates
      containing expanded huntingtin are toxic to neurons, but it remains to be
      determined whether the oligomer or the inclusion is the toxic species.

PMID- 19172116
TI  - Ascariasis in an adolescent with AIDS.

PMID- 19172115
TI  - An emerging concept of prion infections as a form of transmissible cerebral
      amyloidosis.
AB  - Proteins are a major constituent of cells with specific biological functions.
      Besides the primary structure that is simply the sequence of amino acids that
      comprise a protein, the secondary structure represents the first step of folding
      defining its general conformation. The biological functions of proteins are
      directly dependent on the acquisition of their conformation. The same protein can
      have different stable states, which may participate with different functions in
      the cell. The amyloid diseases comprise Alzheimer's and Parkinson's diseases,
      type II diabetes mellitus and systemic amyloidosis. Amyloid fibers are insoluble,
      resistant to proteolysis and show an extremely high content of beta-sheet, in a
      very similar structure to the one observed among prion rods, associated to the
      transmissible spongiform encephalopathies. All these diseases are "infectious" in
      the sense that misfolded beta-sheeted conformers formed in a nucleation process
      in which preformed metastable oligomer acts as a seed to convert a normal isoform
      into an abnormal protein with a misfolded conformation. Only prion infections
      have a proven infectivity in a microbiological sense; some recent observations,
      however, detected the transmissibility of systemic amyloidosis by a prion-like
      mechanism among mice. Prions diseases and amyloidosis present many similar
      aspects of the so-called conformational diseases; according to this
      interpretation the prion infections could be considered as a form of
      transmissible cerebral amyloidosis.

PMID- 19172114
TI  - Biological roles of prion domains.
AB  - In vivo amyloid formation is a widespread phenomenon in eukaryotes. Self
      perpetuating amyloids provide a basis for the infectious or heritable protein
      isoforms (prions). At least for some proteins, amyloid-forming potential is
      conserved in evolution despite divergence of the amino acid (aa) sequences. In
      some cases, prion formation certainly represents a pathological process leading
      to a disease. However, there are several scenarios in which prions and other
      amyloids or amyloid-like aggregates are either shown or suspected to perform
      positive biological functions. Proven examples include self/nonself recognition,
      stress defense and scaffolding of other (functional) polymers. The role of prion
      like phenomena in memory has been hypothesized. As an additional mechanism of
      heritable change, prion formation may in principle contribute to heritable
      variability at the population level. Moreover, it is possible that amyloid-based
      prions represent by-products of the transient feedback regulatory circuits, as
      normal cellular function of at least some prion proteins is decreased in the
      prion state.

PMID- 19172117
TI  - Role of the multichannel intraluminal impedance technique in infants and
      children.
AB  - Recently, multichannel intraluminal impedance (MII) was added to the repertoire
      of tests available to study esophageal (patho)physiology in children. MII has
      since been used in 2 major areas. First, it has been used as a diagnostic test
      for gastroesophageal reflux disease (GERD). The main advantage over traditional
      pH monitoring is its ability to detect both acid and nonacid gastroesophageal
      reflux (GER) and to discern between liquid and gas GER.Although feasible with
      multiple pH sensors, the MII technique routinely detects the proximal extent of a
      GER episode. When a pH sensor is added to the MII-catheter, important information
      about the acidity of a GER event can be gathered.The second area in which the
      role of MII has been investigated is that of esophageal function testing.
      Manometry classically reveals information about esophageal pressure patterns and
      sphincter function, but does not inform us about bolus flow. MII not only detects
      the presence of esophageal flow but also adds information on the direction of
      flow, duration of bolus presence, completeness of bolus clearance, and
      composition of a bolus.The combination of MII with manometry enables
      determination of the relationship between esophageal pressures and flow and,
      therefore, enhances evaluation of esophageal function in terms of assessment of
      mechanisms of esophageal volume clearance. In addition, this technique will
      improve our understanding of (patho)physiological mechanisms in pediatric GERD
      and other esophageal motility disorders.

PMID- 19172118
TI  - Psychological treatments for pediatric functional gastrointestinal disorders.
AB  - Our objective was to systematically review and evaluate behavioral and
      psychological treatments applied to pediatric functional gastrointestinal
      disorders. Electronic searches were conducted in bibliographic databases
      including PubMed, PsychInfo, and Medline. Psychological and behavioral
      interventions were classified into the following 5 primary treatment modalities:
      psychoeducation, behavior therapy/contingency management, relaxation-based
      therapies (including biofeedback and hypnotherapy), and cognitive-behavioral
      therapy (including cognitive-behavioral family therapy). There was a wide
      variation in the quality and quantity of studies within each treatment category.
      Effective interventions generally involved multiple therapeutic components and
      included elements of both individual and family treatment. Psychological
      interventions that combine psychoeducation, relaxation-based therapies, and
      cognitive-behavioral therapy appear superior to standard care (reassurance or
      dietary manipulation) in the elimination of pain and reduction in functional
      disability. Although many psychological treatments demonstrated evidence of
      positive effects, few well-designed randomized controlled trials of psychological
      treatments for functional gastrointestinal disorders exist. More work is needed
      to determine the most potent, essential elements of psychological treatments
      alone or in combination with standard medical intervention, and to establish
      their applicability with diverse populations. Clinical and research implications
      are discussed.

PMID- 19172121
TI  - Childhood esophagitis: then and now.
AB  - OBJECTIVES: It is not known whether the prevalence of childhood esophagitis has
      changed over time. In children, the intraepithelial eosinophil is considered the
      hallmark of esophageal inflammation. This study compares the prevalence of
      intraepithelial eosinophils in esophageal biopsies obtained from 1980-1988 and
      2001-2002. PATIENTS AND METHODS: This study reevaluated all of the esophageal
      biopsies obtained at a single center during 2 periods: 1980-1988 and 2001-2002.
      Histological appearances were characterized and eosinophils per high-power field
      were quantified. RESULTS: In total, 1058 esophageal biopsies from 510 subjects
      were reviewed. Between 1980 and 1988, 247 biopsies from 188 subjects were
      evaluated. Of these, 62 subjects met the criteria for esophageal disease, and 106
      had no specific pathological changes. Between 2001 and 2002, 811 biopsies from
      322 subjects were evaluated. Of these, 132 subjects met the criteria for
      esophageal disease, and 182 had no specific pathological changes. A statistically
      significant increase in the prevalence of esophageal inflammatory disease was
      observed comparing the recent group with the remote group. Eosinophilic
      esophagitis is thought to be distinct from other types of esophagitis in
      pathogenesis, epidemiology, histology, and treatment. Some suggest the prevalence
      of eosinophilic esophagitis has increased in recent years. We sought evidence for
      an increase in histological changes consistent with eosinophilic esophagitis. No
      matter whether histology consistent with eosinophilic esophagitis was defined as
      25, 20, 15, or 10 eosinophils per high-power field, no increase in prevalence was
      found. CONCLUSIONS: This study demonstrated no evidence for a change in the
      density of eosinophilic infiltrates in esophageal biopsies during the 22-year
      study period. The study showed a statistically significant increase in the
      prevalence of esophageal inflammatory disease across the same period.

PMID- 19172119
TI  - Morphological changes of the enteric nervous system, interstitial cells of cajal,
      and smooth muscle in children with colonic motility disorders.
AB  - OBJECTIVES: To evaluate the relation between colonic manometry findings and the
      colonic enteric nervous system, interstitial cells of Cajal, and smooth muscle
      morphology. PATIENTS AND METHODS: Colonic specimens from surgical resections or
      full-thickness biopsy specimens were assessed from a cohort of children who
      underwent colonic manometry before surgery. Colonic manometric patterns were
      subdivided into high-amplitude propagating contractions, low-amplitude
      propagating contractions, absence of contractions, and low-amplitude simultaneous
      contractions. Immunohistochemistry was performed to identify abnormalities in the
      enteric nervous system, interstitial cells of Cajal, and smooth muscle layers.
      RESULTS: Study participants included patients with Hirschsprung disease (n = 4),
      chronic intestinal pseudo-obstruction (n = 1), and idiopathic intractable
      constipation (n = 8). Thirty-seven ganglionic segments were studied.
      Abnormalities in myenteric plexus were recognized in segments of all manometry
      groups, and no differences could be identified when they were compared with
      segments with high-amplitude propagating contractions. All of the segments showed
      an abnormal interstitial cells of Cajal plexus, and no statistical difference
      could be identified between the 4 groups (n = 0.08). Homogeneous expression of
      smooth muscle actin was observed in all of the segments. CONCLUSIONS: In this
      cohort we were unable to classify specific manometric findings as reflective of
      myopathic or neuropathic abnormalities in patients with motility disorders.
      Caution should be used when predicting the type of neuromuscular disorder based
      on colonic manometry.

PMID- 19172120
TI  - 14 years of eosinophilic esophagitis: clinical features and prognosis.
AB  - OBJECTIVE: To determine the natural history of treated and untreated eosinophilic
      esophagitis (EE) and examine the presenting symptoms of EE. PATIENTS AND METHODS:
      Retrospective and prospective chart review of all patients diagnosed with EE at
      The Children's Hospital of Philadelphia. EE was defined as greater than 20
      eosinophils per high power field after treatment with reflux medications.
      RESULTS: We identified 620 patients in our database in the last 14 years and 330
      patients with greater than 1 year of follow-up for analysis. The number of new EE
      patients has increased on an annual basis. Of the patients presenting with EE,
      68% were younger than 6 years old. Reflux symptoms and feeding issues/failure to
      thrive were the most common presenting symptoms for EE. Eleven patients had
      resolution of all of their food allergies and 33 patients had resolutions of some
      of their food allergies. No patients have progression of EE into other
      gastrointestinal disorders. CONCLUSIONS: EE is a chronic disease with less than
      10% of the population developing tolerance to their food allergies. EE does not
      progress into other gastrointestinal diseases.

PMID- 19172122
TI  - "pH-Only" acid reflux events in infants during later phases of the feeding cycle
      are less acidic and cleared more efficiently than classic 2-phase acid reflux
      events.
AB  - BACKGROUND: Gastroesophageal acid exposure in infants is a function of 4 acid
      gastroesophageal reflux (AGER) types: classic 2-phase, single-phase, and pH-only
      events (POEs), as well as rereflux episodes. In symptomatic infants, classic 2
      phase events and POEs make up the majority of total AGER events and AGER events
      lasting 5 minutes or longer, and are responsible for the majority of total
      gastroesophageal acid exposure. Also, in symptomatic infants, chemical clearance
      efficiency of classic 2-phase events has been shown to be influenced by feeding.
      Pathogenicity of AGER involves variables that include frequency, duration, and pH
      of AGER events. The purpose of this investigation was to compare classic 2-phase
      episodes and POEs on the basis of these variables during discrete periods related
      to feeding. PATIENTS AND METHODS: Impedance/pH tracings from 12 symptomatic
      infants (median age 20 weeks) were examined. Mean frequencies, durations, and
      nadir pH values were calculated during feeding, the first hour postprandial
      (1stPP), the second hour postprandial (2ndPP), and fasting. RESULTS: Compared
      with classic 2-phase events, POEs were cleared significantly more efficiently
      during 1stPP (3-fold, P = 0.02), 2ndPP (3-fold, P = 0.0001), and fasting (4.5
      fold, P < 0.0001), and were less acidic during 2ndPP (1.9 +/- 0.15 vs 2.6 +/-
      0.07, P = 0.0005) and fasting (1.5 +/- 0.12 vs 2.9 +/- 0.07, P < 0.0001). Whereas
      clearance of classic 2-phase events became increasingly less efficient, clearance
      of POEs did not fluctuate significantly during the course of the feeding cycle.
      CONCLUSIONS: The lower acidity and more rapid clearance during 2ndPP and fasting
      suggest that POEs are likely to have a different clinical impact (compared with
      classic 2-phase AGER events) during later phases of the feeding cycle.

PMID- 19172123
TI  - Fecal calprotectin and lactoferrin as noninvasive markers of pediatric
      inflammatory bowel disease.
AB  - OBJECTIVE: To evaluate whether fecal calprotectin (FC) and fecal lactoferrin (FL)
      can be used as noninvasive markers in children and young people (4-17 years) with
      active inflammatory bowel disease (IBD). PATIENTS AND METHODS: Stool samples were
      collected from 3 groups of children: those with active IBD, control individuals
      with other gastrointestinal (GI) diseases (GI control) and control individuals
      with no GI disease (non-GI control). The number of patients for the FC assay was
      as follows: IBD = 26, GI control = 30, non-GI control = 25. The number of
      patients for the FL assay was as follows: IBD = 24, GI control = 26, non-GI = 24.
      FC and FL were measured by use of enzyme-linked immunoassays. RESULTS: The median
      concentrations of FC and FL in isolation, and their interaction, were
      significantly higher in the IBD group than in the GI and non-GI control groups (P
      < 0.001). Although the area under the curve, sensitivity, and specificity for FC,
      FL, and FC x FL interaction were significantly better than chance, FL
      consistently had the lowest area under the curve, and FC x FL consistently had
      the highest area under the curve. CONCLUSIONS: FC and FL are both significantly
      elevated in children with IBD, and the interaction of these 2 biomarkers may
      produce a better initial diagnostic test compared with their use in isolation.

PMID- 19172124
TI  - Use of complementary medicine in pediatric patients with inflammatory bowel
      disease: results from a multicenter survey.
AB  - OBJECTIVES: We examined the use of complementary and alternative medicine (CAM)
      at 3 US pediatric medical centers, comparing a group of children with
      inflammatory bowel disease (IBD) with children presenting with chronic
      constipation. MATERIALS AND METHODS: Surveys were administered by postal mail and
      at pediatric IBD centers in San Francisco, Houston, and Atlanta from 2001 to
      2003. A comparison group consisting of pediatric patients with chronic
      constipation also was surveyed. Data were analyzed by t tests and by exact tests
      of contingency tables. RESULTS: In all, 236 surveys were collected from the IBD
      group; 126 surveys were collected from the chronic constipation comparison group.
      CAM therapies were used by 50% in the IBD group and 23% in the chronic
      constipation group. The overall regional breakdown of CAM use in IBD revealed no
      differences, although the types of CAM therapy used varied by site. The most
      commonly used CAM therapies in the IBD group were spiritual interventions (25%)
      and nutritional supplements (25%). Positive predictors for CAM use in IBD include
      the patient's self-reported overall health, an increase in the number of side
      effects associated with allopathic medications, white ethnicity, and parental
      education beyond high school. CONCLUSIONS: This is the first US study to
      characterize CAM use in pediatric patients with IBD with another chronic
      gastrointestinal disorder. CAM use was twice as common with the IBD group
      compared with the chronic constipation group. Regional variations exist with the
      types of CAM therapy used. Practitioners should know that half of their pediatric
      patients with IBD may be using CAM in conjunction with or as an alternative to
      other treatments and that certain predictors can help identify those using CAM
      therapies.

PMID- 19172125
TI  - Transition of adolescents with inflammatory bowel disease from pediatric to adult
      care: a survey of adult gastroenterologists.
AB  - OBJECTIVES: Transition of patients with inflammatory bowel disease (IBD) from
      pediatric to adult providers requires preparation. Gastroenterologists for adult
      patients ("adult gastroenterologists") may have expectations of patients that are
      different from those of pediatric patients. We sought to explore the perspectives
      of adult gastroenterologists caring for adolescents and young adults with IBD, to
      improve preparation for transition. MATERIALS AND METHODS: A survey sent to 1132
      adult gastroenterologists caring for patients with IBD asked physicians to rank
      the importance of patient competencies thought necessary in successful transition
      to an adult practice. Providers reported which problems occurred in patients with
      IBD transitioning to their own practice. Adult gastroenterologists were asked
      about medical and developmental issues that are unique to adolescence. RESULTS: A
      response rate of 34% was achieved. Adult gastroenterologists reported that young
      adults with IBD often demonstrated deficits in knowledge of their medical history
      (55%) and medication regimens (69%). In addition, 51% of adult
      gastroenterologists reported receiving inadequate medical history from pediatric
      providers. Adult providers were less concerned about the ability of patients to
      identify previous and current health care providers (19%), or attend office
      visits by themselves (15%). Knowledge of adolescent medical and developmental
      issues was perceived as important by adult gastroenterologists; however, only 46%
      felt competent addressing the developmental aspects of adolescents. CONCLUSIONS:
      For successful transition, adolescents and young adults with IBD need improved
      education about their medical history and medications. Pediatric providers need
      to improve communication with the receiving physicians. In addition, adult
      providers may benefit from further training in adolescent issues. Formal
      transition checklists and programs may improve the transition of patients with
      IBD from pediatric to adult care.

PMID- 19172126
TI  - Is endoscopic retrograde cholangiopancreatography valuable and safe in children
      of all ages?
AB  - OBJECTIVE: To evaluate indications, findings, therapies, safety, and technical
      success of endoscopic retrograde cholangiopancreatography (ERCP) in children of
      the Emma Children's Hospital Academic Medical Centre in Amsterdam, the
      Netherlands. DESIGN: Descriptive. Retrospective analysis by medical records.
      PATIENTS AND METHODS: Information was obtained by chart review of patients
      between 0 and 18 years who underwent ERCP from 1995 to 2005 in our center. The
      following data were analyzed: indications, findings, therapies, safety, and
      technical success. Success was defined as obtaining accurate diagnostic
      information or succeeding in endoscopic therapy. RESULTS: Sixty-one children (age
      3 days to 16.9 years, mean age 7.0 years) underwent a total of 99 ERCPs. Of those
      patients, 51% (31/61) were younger than 1 year, 84% had biliary indications, and
      16% had pancreatic indications for the performance of ERCP. The complication rate
      was 4% (4/99) and included substantial pancreatitis and mild irritated pancreas.
      No complications occurred in children younger than 1 year. CONCLUSIONS: ERCP is a
      safe and valuable procedure for children of all ages with suspicion of
      pancreaticobiliary diseases. Indications for ERCP are different for children and
      adults. A laparotomy could be prevented in 12% of children with suspicion of
      biliary atresia. Further research is required to determine the role of MRCP
      versus ERCP.

PMID- 19172127
TI  - Wilson disease in children: analysis of 57 cases.
AB  - OBJECTIVES: Wilson disease (WD) has a wide spectrum of clinical manifestations.
      Affected children may be entirely asymptomatic and the diagnosis problematic.
      Herein we present the clinical and laboratory characteristics of 57 children with
      WD and point out the diagnostic difficulties in a pediatric population. PATIENTS
      AND METHODS: Clinical and laboratory data were collected from 57 consecutive
      children with WD. Evaluation included detailed physical examination, conventional
      laboratory testing, genetic analysis, and liver biopsy. RESULTS: The mean age at
      diagnosis was 9.27 +/- 3.62 years (range 4 months-18 years). Twenty patients were
      symptomatic, 19 were referred because of abnormal liver function test results
      and/or hepatomegaly, and 18 received their diagnoses after family screening.
      Twenty-two patients had both Kayser-Fleischer ring and decreased serum
      ceruloplasmin levels, 13 had urinary copper excretion after penicillamine
      challenge >1600 microg/24 hours, and 3 had liver copper content >250 microg/g dry
      weight. Of the remaining 19 patients, 17 had both low serum ceruloplasmin <or=20
      mg/dL and increased urinary copper excretion, >75 microg/24 hours before, or
      >1000 microg/24 hours after penicillamine challenge. In 2 patients with equivocal
      cases who had serum ceruloplasmin 26 mg/dL, the diagnosis was confirmed by
      genetic analysis. No correlation was found between specific mutations and the
      disease phenotypic expression. Chelating therapy was well tolerated, and the
      outcome was satisfactory. CONCLUSIONS: WD in children may be obscure and requires
      extensive investigation to establish the diagnosis. Genetic analysis is needed in
      equivocal cases.

PMID- 19172128
TI  - British paediatric surveillance unit study of biliary atresia: outcome at 13
      years.
AB  - BACKGROUND: Little information is available on contemporary, prospectively
      collected data on the long-term outcome of national cohorts of children with
      biliary atresia. OBJECTIVE: This study aimed to describe the current outcome of a
      national cohort of children with biliary atresia. PATIENTS AND METHODS: All 93
      cases of biliary atresia in the United Kingdom and Ireland diagnosed between
      March 1993 and February 1995 were followed up prospectively. RESULTS: A total of
      91 children underwent Kasai portoenterostomy in 15 individual centres. Only 2
      centres treated more than 5 children annually. Median age at last follow-up was
      12 years (range 0.25-14). Fifteen children (16%) have died: 10 after unsuccessful
      portoenterostomy, 1 of sepsis after successful portoenterostomy, and 4 after
      liver transplantation. Forty-two (45%) underwent liver transplantation at a
      median age of 1 year (range 0.5-9), with 90% survival. All 41 children with
      failed portoenterostomy (and 2 without portoenterostomy) died or underwent liver
      transplantation at a median age of 0.8 years (range 0.25-6.5). When the
      portoenterostomy was successful, 40 of 50 patients (80%) are alive without liver
      transplantation. The 13-year actuarial survival without liver transplantation is
      43.8% overall and is better in children treated at centres that treat more than 5
      cases yearly (54% vs 27.3%, P = 0.005). CONCLUSIONS: If the portoenterostomy is
      successful, then few children with biliary atresia will need transplantation
      before adolescence. Children with biliary atresia should be treated in
      experienced centres to maximize the chance of successful surgery.

PMID- 19172129
TI  - Galacto-oligosaccharides are bifidogenic and safe at weaning: a double-blind
      randomized multicenter study.
AB  - OBJECTIVES: The primary objective of this study was to determine the bifidogenic
      effect of galacto-oligosaccharides (GOS) in a follow-on formula and the effects
      on other intestinal bacteria. Secondary objectives were the effects on stool
      characteristics, growth, and general well-being. PARTICIPANTS AND METHODS: In a
      multicenter, double-blind study, 159 healthy infants, formula-fed at enrollment
      (at 4-6 months), were randomized to an experimental follow-on formula
      supplemented with 5 g/L (GOS) (77 infants), or to a standard follow-on formula
      (control, 82 infants). Infants were evaluated at enrollment (study day 1 = sd1),
      after 6 weeks (study day 2 = sd2), and after an additional 12 weeks (study day 3
      = sd3). At each study day, a fresh stool sample for the bacterial counts was
      collected, and the growth parameters were measured. At sd2, urinary specimens
      were collected for the evaluation of urinary osmolarity. RESULTS: At sd2 and sd3,
      the GOS group had a higher median number (colony-forming units per gram of stool)
      of bifidobacteria than did the control group (sd2 GOS 9.2 x 10(9) vs control 4.4
      x 10(9), P = 0.012); (sd3 GOS 7.2 x 10(9) vs control 2.4 x 10(9), P = 0.027).
      Other bacteria did not show any significant differences between the 2 groups at
      all study days. The GOS produced softer stools but had no effect on stool
      frequency. The urinary osmolarity (mOsm/L) at sd2 was comparable in both groups.
      Supplementation had no influence on the incidence of gastrointestinal side
      effects or on the growth of the infants. CONCLUSIONS: These data indicate that
      the addition of GOS (5 g/L) to a follow-on formula positively influences the
      bifidobacteria flora and the stool consistency in infants during the
      supplementation period at weaning. No local or systemic side effects were
      recorded.

PMID- 19172130
TI  - Zinc therapy for diarrhoea improves growth among Bangladeshi infants 6 to 11
      months of age.
AB  - OBJECTIVES: We assessed the effect of zinc for the treatment of diarrhoea
      implemented at the community level on physical growth among children 6 to 35
      months of age. METHODS: The service areas of 30 community health workers in the
      Matlab field site of International Centre for Diarrhoeal Disease Research,
      Bangladesh, were randomly allocated to the intervention or comparison study arm.
      Between November 1998 and October 2000, caretakers of 3- to 59-month-old children
      with diarrhoea in both intervention and comparison areas were offered oral
      rehydration solution and feeding advice, and severe episodes were referred for
      facility-based care. The caretakers of the children in the intervention area were
      additionally offered 20 mg/day elemental zinc for 14 days as adjunct treatment
      for each diarrhoea episode. Weight and length of children who were 6 to 11 months
      of age at the beginning of the study were measured every 2 months for 2 years.
      Rates of length and weight gains were compared between children living in
      intervention and control arms using a latent growth model. RESULTS:
      Characteristics of children living in control and intervention areas were
      similar, except that more children living in intervention areas were underweight
      at baseline (44 vs 35%; P = 0.02). Children living in intervention clusters
      gained slightly more weight and length than children in the control clusters
      (86.4 g/year and 2.8 mm/year, respectively). CONCLUSIONS: The therapeutic use of
      zinc along with oral rehydration solution for community-based diarrhoea
      management may have a small positive benefit on the rates of growth among
      children younger than 3 years of age.

PMID- 19172131
TI  - Cytokine responses in very low birth weight infants receiving glutamine-enriched
      enteral nutrition.
AB  - OBJECTIVE: Very low birth weight (VLBW) infants receiving glutamine-enriched
      enteral nutrition may present with a lower infection rate, which may result from
      enhanced antimicrobial innate or Th1 cytokine responses. We investigated whether
      glutamine-enriched enteral nutrition in VLBW infants increased these cytokine
      responses following in vitro stimulation of whole blood cells. METHODS: In a
      double-blind, placebo-controlled, randomized controlled trial, VLBW infants
      (gestational age <32 weeks and/or birth weight <1500 g) received enteral
      glutamine supplementation (0.3 g x kg(-1) x day(-1)) or isonitrogenous placebo
      supplementation (alanine) between days 3 and 30 of life. Cytokine responses
      following in vitro whole blood cell stimulation with anti-(alpha)CD3/alphaCD28 or
      lipopolysaccharide were analyzed by cytometric bead array at 3 time points:
      before the start of the study, at day 7 of life, and at day 14 of life. RESULTS:
      Baseline patient and nutritional characteristics were not different between
      groups. At least 2 blood samples were analyzed in 25 of 52 (48%) and 38 of 50
      (76%) infants in the glutamine-supplemented and control groups, respectively.
      Glutamine-enriched enteral nutrition was not associated with significant
      alterations in cytokine responses (interferon-gamma, tumor necrosis factor-alpha,
      interleukin [IL]-2, IL-4, IL-5, and IL-10) of peripheral blood cells upon
      stimulation with either anti-alphaCD3/alphaCD28 or lipopolysaccharide.
      CONCLUSIONS: We hypothesize that glutamine-enriched enteral nutrition decreases
      the infection rate in VLBW infants by influencing the mucosal and not the
      systemic immune system.

PMID- 19172132
TI  - Posterior reversible encephalopathy syndrome following infliximab infusion.

PMID- 19172133
TI  - Crohn disease of the neovagina and augmented bladder in a child born with cloacal
      exstrophy.

PMID- 19172134
TI  - Colon cancer in a 16-year-old girl: signet-ring cell carcinoma without
      microsatellite instability--an unusual suspect.

PMID- 19172135
TI  - Selected summary. Extrahepatic biliary atresia (EHBA) is still a significant
      medical and economic burden to patients and families.

PMID- 19172136
TI  - Fecal beta-defensin-2 in children with inflammatory bowel diseases.
AB  - Defensins, endogenous antibiotic peptides, are part of the intestinal epithelial
      barrier. In this pilot study we analyzed the possibility of measuring fecal beta
      defensin-2 (HBD2) in comparing inflammatory and noninflammatory conditions. In
      samples from healthy control individuals, low levels of HBD2 were detectable,
      which markedly rose under inflammatory conditions (P = 0.0002 vs normal control
      individuals), the highest levels being observed in patients with ulcerative
      colitis (median 356 ng/g, range 40-527). Despite frank inflammation, Crohn
      disease patients with colitis had significantly lower, albeit enhanced, HBD2
      levels than did ulcerative colitis patients. These data confirm the possibility
      of quantifying HBD2 in feces and indicate that colitis in Crohn disease and
      colitis in ulcerative colitis differ from each other with respect to their
      ability to secrete HBD2.

PMID- 19172137
TI  - Drugs for HIV Infection.

PMID- 19172138
TI  - More resistance to oseltamivir (Tamiflu).

PMID- 19172139
TI  - Implantable cardioverter defibrillators.

PMID- 19172140
TI  - Tetrabenazine (Xenazine) for Huntington's chorea.

PMID- 19172142
TI  - General or locoregional anesthesia for elective carotid endarterectomy: which
      local anesthetic can we use?

PMID- 19172143
TI  - Prospective randomized, blind comparison of ropivacaine and levobupivacaine for
      superficial plexus anesthesia in carotid endoarterectomy.
AB  - BACKGROUND: The authors performed a study to evaluate if the onset time, duration
      of sensory block, and quality of postoperative analgesia in superficial cervical
      plexus anesthesia with 0.5% levobupivacaine (1 mg/kg) was greater than 0.75%
      ropivacaine (1.5 mg/kg). METHODS:  DESIGN: randomized, double-blind study.
      SETTING: University teaching hospital. PARTICIPANTS: 28 consecutive patients
      undergoing elective carotid thromboendoarterectomy were randomized into two
      groups. INTERVENTIONS: patients received either 1 mg/kg of 0.5% levobupivacaine
      (N.=15), or 1.5 mg/kg of 0.75% ropivacaine (N.=13). We assessed the onset time
      (pinprick test), duration of sensory block, and postoperative analgesia with the
      two drugs. RESULTS: Onset time of sensory block was 20+/-6 min with ropivacaine
      and 29+/-8 min with levobupivacaine (P=0.003). Intraoperatively we used different
      total doses of lidocaine, with the median (interquartile range) dose of 50 (40
      100) mg for ropivacaine and 130 (60-180) mg for levobupivacaine (P=0.05). The
      first pain medication was requested after 12+/-0.4 h by ropivacaine patients and
      after 11+/-1.6 h by levobupivacaine patients (P=0.5). CONCLUSION: No beneficial
      effect was noted in the quality of nerve block or patient's satisfaction for 0.5%
      levobupivacaine when compared to 0.75% ropivacaine.

PMID- 19172144
TI  - The 2008 international guidelines for management of severe sepsis and septic
      shock: merits and weaknesses.
AB  - The Guidelines are intended to provide standard guidance for the care of patients
      by grouping evidence-based interventions into bundles that can be easily used by
      clinicians to improve patient outcome. The 2008 International guidelines for
      management of severe sepsis and septic shock is a large and extraordinary update
      of the literature offered by current leaders in the field. Unfortunately, as a
      consensus of experts, most of whom expressed their opinions by voting, these
      guidelines do not always represent the state of the art. Furthermore, they can
      change if new participants take part in the process. By considering the merits
      and weaknesses of practice guidelines, we conclude that guidelines cannot replace
      a physician's judgments, but rather should be a starting point for more robust
      and proficient scientific evidence.

PMID- 19172145
TI  - A year in review in Minerva Anestesiologica, 2008. I Critical Care. Experimental
      and clinical studies.

PMID- 19172146
TI  - Discovering chemical modifiers of oncogene-regulated hematopoietic
      differentiation.
AB  - It has been proposed that inhibitors of an oncogene's effects on multipotent
      hematopoietic progenitor cell differentiation may change the properties of the
      leukemic stem cells and complement the clinical use of cytotoxic drugs. Using
      zebrafish, we developed a robust in vivo hematopoietic differentiation assay that
      reflects the activity of the oncogene AML1-ETO. Screening for modifiers of AML1
      ETO-mediated hematopoietic dysregulation uncovered unexpected roles of COX-2- and
      beta-catenin-dependent pathways in AML1-ETO function. This approach may open
      doors for developing therapeutics targeting oncogene function within leukemic
      stem cells.

PMID- 19172149
TI  - Is Brucella an enteric pathogen?

PMID- 19172147
TI  - A new perspective on radiation resistance based on Deinococcus radiodurans.
AB  - In classical models of radiation toxicity, DNA is the molecule that is most
      affected by ionizing radiation (IR). However, recent data show that the amount of
      protein damage caused during irradiation of bacteria is better related to
      survival than to DNA damage. In this Opinion article, a new model is presented in
      which proteins are the most important target in the hierarchy of macromolecules
      affected by IR. A first line of defence against IR in extremely radiation
      resistant bacteria might be the accumulation of manganese complexes, which can
      prevent the production of iron-dependent reactive oxygen species. This would
      allow an irradiated cell to protect sufficient enzymatic activity needed to
      repair DNA and survive.

PMID- 19172150
TI  - Vestibular function after spinal cord injury: preliminary results.
AB  - STUDY DESIGN: The excitability of the vestibular apparatus and pathways was
      studied in 10 patients with acute spinal cord injury (ASCI) and in 7 patients
      with chronic spinal cord injury (CHSCI). OBJECTIVES: Proprioceptive input that
      may be lost after spinal cord injury (SCI) is needed for integration with
      vestibular signals to produce proper postural control and perception of movement.
      This study examined whether there is a change in vestibular excitability after
      the disruption of the afferent proprioceptive input due to the spinal cord
      lesion. This study was carried out at Spine Injury Centre and Institute of
      Rehabilitation, Belgrade, Serbia. METHODS: A total of 10 patients with ASCI and 7
      with CHSCI were compared to a group of 50 age-matched healthy subjects. The
      excitability of the vestibular pathways was studied by means of a modified
      caloric test in which the duration of postcaloric nystagmus was measured.
      RESULTS: ASCI patients with cervical lesions showed significantly reduced
      response durations (P<0.05). There was no difference in control values for ASCI
      and for CHSCI patients with thoracic or lumbal lesions. There was no difference
      in control values for cervical CHSCI patients. CONCLUSIONS: These results suggest
      that the vestibular response to caloric stimulation is supported by spinally
      mediated sensory input and that the loss of such input is compensated for over
      time. Further, these results show that the caloric test may be a useful tool for
      assessing the degree to which SCI disrupts multisensory integration in the
      vestibular system and tracking the process of reintegration.

PMID- 19172151
TI  - Properties and outcomes of spinal rehabilitation units in four countries.
AB  - OBJECTIVE: Compare rehabilitation after spinal cord lesions (SCL) in different
      countries. DESIGN: Multicenter comparative study. SETTING: Four spinal
      rehabilitation units, in Denmark, Russia, Lithuania and Israel. SUBJECTS: 199 SCL
      patients. INTERVENTIONS: Information was collected about unit properties,
      rehabilitation objectives, American Spinal Injury Association (ASIA) scale and
      spinal cord independence measure (SCIM) assessments, and patient data. chi (2)
      test, t-test, ANOVA and ANCOVA were used for statistical analysis. MAIN OUTCOME
      MEASURES: Time from lesion onset to admission for rehabilitation (TAR), length of
      stay in rehabilitation (LOS), SCIM and spinal cord ability realization
      measurement index (SCI-ARMI) scores, SCIM gain, SCI-ARMI gain and rehabilitation
      efficiency (RE). RESULTS: Differences were found between the units in
      rehabilitation objectives, facilities and special equipment for rehabilitation.
      Staff/bed ratio was 1.7 in Lithuania and Denmark, 1.1 in Israel and 0.9 in
      Russia. Russian patients were the youngest and had the most severe lesions among
      participating units. Admission SCIM and SCI-ARMI were the lowest in Israel:
      25.1+/-17.2 and 34.3+/-17.3. TAR was highest in Russia (12.4 month) and lowest in
      Israel (2 weeks; P<0.01). LOS was longest in Denmark (176.9 days; P<0.001). SCIM
      score at the end of rehabilitation was highest in Denmark (67.3+/-23). SCIM gain
      and SCI ARMI gain were highest in Israel (36.9+/-18.3 and 38.5+/-19.4,
      respectively) and lowest in Russia (P<0.001). RE was highest in Lithuania and
      lowest in Denmark (P<0.001). CONCLUSIONS: In the participating units, SCL
      rehabilitation outcomes depend on SCL severity and unit-specific properties. A
      moderately delayed rehabilitation with long LOS achieved high functioning, and
      early or slightly delayed rehabilitation combined with shorter LOS achieved high
      functional gain or efficiency.

PMID- 19172152
TI  - Non-pharmacological treatment and prevention of bone loss after spinal cord
      injury: a systematic review.
AB  - OBJECTIVE: Review the literature on non-pharmacological prevention and treatment
      of osteoporosis after spinal cord injury (SCI). METHODS: PubMed, EMBASE and the
      Cochrane Controlled Trials Register were searched. All identified papers were
      read by title, abstract and full-length article when relevant. Hand search of the
      articles' sources identified additional papers. For included studies, the level
      of evidence was determined. RESULTS: No studies conclusively showed an effective
      intervention. However, there are few randomized controlled trials (RCTs), and
      those that exist assess interventions and outcome measures that could be
      improved. Five studies on weight-bearing early post-injury are conflicting, but
      standing or walking may help retain bone mineral. In the chronic phase, there was
      no effect of weight bearing (12 studies). One study found that an early
      commencement of sports after SCI improved bone mineral, and the longer the period
      of athletic career, the higher the (leg) bone mineral. Early after SCI, there may
      be some effects of electrical stimulation (ES) (five studies). Chronic-phase ES
      studies vary (14 studies, including mixed periods after injury), but improvement
      is seen with longer period of training, or higher frequency or stimulus
      intensity. Improvements correspond to trabecular bone in the distal femur or
      proximal tibia. Impact vibration and pulsed electromagnetic fields may have some
      positive effects, whereas pulsed ultrasound does not. Six studies on the
      influence of spasticity show inconsistent results. CONCLUSIONS: Bone mineral
      should be measured around the knee; the length and intensity of the treatment
      should be sufficiently long and high, respectively, and should commence early
      after SCI. If bone mineral is to remain, the stimulation has to be possibly
      continued for long term. In addition, RCTs are necessary.

PMID- 19172153
TI  - Progression of spinal cord atrophy by traumatic or inflammatory myelopathy in the
      pediatric patients: case series.
AB  - STUDY DESIGN: Case series. OBJECTIVE: To present spinal cord atrophy in pediatric
      patients who had spinal cord injury developed after trauma or acute transverse
      myelitis, and had no motor recovery later. SETTING: Department of Rehabilitation
      Medicine, Tertiary National University Children's Hospital, Seoul, Korea.
      METHODS: Case series. RESULTS: Two pediatric patients with paraplegia due to
      acute transverse myelitis and one pediatric patient with paraplegia due to
      traumatic myelopathy were included in this case series. Their initial MRI
      (magnetic resonance imaging) findings were spinal cord swelling and high signal
      intensity in T2-weighted image. After several months, they had no motor recovery
      and showed no change of neurological level, though they underwent steroid and
      physical therapy. A follow-up MRI revealed spinal cord atrophy. CONCLUSION: If a
      pediatric patient with traumatic or inflammatory spinal cord injury does not show
      motor recovery after several months, spinal cord atrophy must be considered.

PMID- 19172154
TI  - A pilot study examining correlates of body image among women living with SCI.
AB  - STUDY DESIGN: Cross-sectional pilot study. OBJECTIVES: To explore correlates of
      body image among women with spinal cord injury (SCI), within the framework of
      Cash's cognitive behavioral model of body image. SETTING: Hamilton, Ontario,
      Canada. METHODS: Women with SCI (N=11, 64% with tetraplegia) reported their
      functional and appearance body image (Adult Body Satisfaction Questionnaire). A 3
      day recall of leisure time physical activity (LTPA), three measures of body
      composition (that is, weight, waist circumference, body fat) and several
      demographic variables were assessed as potential correlates. RESULTS: Appearance
      satisfaction was negatively correlated with all three measures of body
      composition and positively correlated with years postinjury. Functional
      satisfaction was positively correlated with years postinjury, and negatively
      correlated with various LTPA variables. CONCLUSION: Functional and appearance
      body image may improve with time following SCI. Body composition may impact
      satisfaction with physical appearance for some women. The negative relationship
      between LTPA and functional satisfaction merits further examination, as
      functional dissatisfaction may motivate individuals to engage in certain types
      and intensities of LTPA. Correlates of body image differ between appearance and
      functional satisfaction. Future research should examine appearance and functional
      satisfaction separately among women with SCI.

PMID- 19172155
TI  - Equivalent stimulation of naive and memory CD8 T cells by DNA vaccination: a
      dendritic cell-dependent process.
AB  - CD8 T-cell priming following DNA vaccination has been shown to confer protection
      against infections and tumors. These vaccines, however, have been disappointing
      in their ability to boost memory responses in prime-boost settings. We recently
      found that migratory dendritic cell (DC) subsets inefficiently stimulate memory
      CD8 T cells, raising the possibility that the poor boosting capacity of DNA
      encoded antigens might relate to their presentation by subsets of DCs that are
      only capable of efficiently stimulating naive T cells. Here, we show that DCs are
      required for T-cell priming in vivo following intradermal immunization with DNA
      encoded antigens and that epidermal Langerhans cells are relatively unimportant.
      We then provide evidence that naive and memory CD8 T cells respond equally to DNA
      encoded antigen. These findings show that immunization to DNA-encoded antigens is
      strongly DC-dependent and that the failure to boost memory T-cell immunity
      efficiently is not a consequence of a differential capacity of this form of
      antigen to stimulate naive or memory T cells.

PMID- 19172156
TI  - Using histone deacetylase inhibitors to enhance Foxp3(+) regulatory T-cell
      function and induce allograft tolerance.
AB  - The histone/protein deacetylase inhibitor (HDACi), trichostatin A (TsA),
      increases the production and suppressive function of Foxp3(+) regulatory T cells
      (T(regs)), at least in part, by promoting the acetylation of Foxp3 protein
      itself. Acetylation of Foxp3 is required for effective binding of Foxp3 to the
      promoter of the interleukin-2 (IL-2) gene and the suppression of IL-2 expression.
      We have sought to identify agents that had similar effects on T(regs), but
      without the associated toxicity of TsA. This review summarizes the contrasting
      effects of various HDACis on T(reg) functions in vitro and in vivo. Agents that
      block primarily class I HDAC had minimal or no effect on T(reg) suppression,
      whereas multiple inhibitors of both class I and class II HDAC enhanced T(reg)
      suppression in vitro and in vivo. These data indicate tools for further analysis
      of T(reg) functions, and point to a critical role of class II HDAC in the
      regulation of T(regs). Such knowledge has direct implications for the development
      of in vivo approaches to treat autoimmune and other inflammatory diseases.

PMID- 19172157
TI  - Genetic variants in multidrug and toxic compound extrusion-1, hMATE1, alter
      transport function.
AB  - hMATE1 (human multidrug and toxin compound extrusion-1; encoded by SLC47A1) is
      thought to have an important function in the renal and hepatic elimination of
      drugs, endogenous compounds and environmental toxins. The goals of this study
      were to identify genetic variants of hMATE1 and to determine their effects on
      hMATE1 transport function. We identified four synonymous and six nonsynonymous,
      coding region variants in DNA samples from 272 individuals (68 Caucasians, 68
      African Americans, 68 Asian Americans and 68 Mexican Americans). The overall
      prevalence of hMATE1 nonsynonymous variants was relatively low with three
      singleton variants and three variants having allele frequencies > or =2% in a
      specific ethnic group. The nonsynonymous hMATE1 variants were constructed and
      stably transfected into HEK-293 cells. Uptake studies using four known hMATE1
      substrates (paraquat, metformin, tetraethylammonium and oxaliplatin) were
      performed in cells transfected with hMATE1 reference or variants. We found that
      two singleton variants, G64D and V480M, produced a complete loss of function for
      all four tested substrates whereas three polymorphic variants (allele frequencies
      > or =2%), L125F, V338I and C497S, significantly altered the transport function
      in a substrate-dependent manner. Confocal microscopy studies were consistent with
      functional studies suggesting that the altered function of the variants was due
      to altered localization to the plasma membrane. These data suggest that
      nonsynonymous variants in hMATE1 may alter drug disposition and ultimately affect
      clinical drug response.

PMID- 19172158
TI  - Education as a predictor of quality of life outcomes among disadvantaged men.
AB  - Higher educational levels along with other factors such as literacy and
      communication with physicians have been associated with better outcomes for men
      with prostate cancer, but little research has focused on the relationship of
      educational attainment to self-efficacy for interacting with physicians been
      conducted on its effect on self-efficacy and health-related quality of life
      (HRQOL) among low-income, uninsured men. Data from 425 low-income, uninsured men
      with prostate cancer enrolled in UCLA's Men's Health Study were examined. We
      found that men with higher and lower education levels, including those who did
      not complete high school, had similar HRQOL and self-efficacy outcomes. Because
      of the close relationship between income and education, broader studies into the
      associations of these variables and prostate cancer outcomes are needed.

PMID- 19172159
TI  - Connecting the dots.

PMID- 19172161
TI  - Making scents out of how olfactory neurons are ordered in space.

PMID- 19172162
TI  - Whither proBDNF?

PMID- 19172163
TI  - Too much Sonic, too few neurons.

PMID- 19172164
TI  - PML: a tumor suppressor essential for neocortical development.

PMID- 19172165
TI  - Sleep on it.

PMID- 19172166
TI  - Exit chloride, enter glutamate.

PMID- 19172168
TI  - More attention and greater awareness in the scientific study of magic.

PMID- 19172169
TI  - Metric Learning Using Iwasawa Decomposition.
AB  - Finding a good metric over the input space plays a fundamental role in machine
      learning. Most existing techniques use the Mahalanobis metric without
      incorporating the geometry of positive matrices and experience difficulties in
      the optimization procedure. In this paper we introduce the use of Iwasawa
      decomposition, a unique and effective parametrization of symmetric positive
      definite (SPD) matrices, for performing metric learning tasks. Unlike other
      previously employed factorizations, the use of the Iwasawa decomposition is able
      to reformulate the semidefinite programming (SDP) problems as smooth convex
      nonlinear programming (NLP) problems with much simpler constraints. We also
      introduce a modified Iwasawa coordinates for rank-deficient positive semidefinite
      (PSD) matrices which enables the unifying of the metric learning and linear
      dimensionality reduction. We show that the Iwasawa decomposition can be easily
      used in most recent proposed metric learning algorithms and have applied it to
      the Neighbourhood Components Analysis (NCA). The experimental results on several
      public domain datasets are also presented.

PMID- 19172170
TI  - AN OPTIMAL-PATH APPROACH FOR NEURAL CIRCUIT RECONSTRUCTION.
AB  - Neurobiologists are collecting large amounts of electron microscopy image data to
      gain a better understanding of neuron organization in the central nervous system.
      Image analysis plays an important role in extracting the connectivity present in
      these images; however, due to the large size of these datasets, manual analysis
      is essentially impractical. Automated analysis, however, is challenging because
      of the difficulty in reliably segmenting individual neurons in 3D. In this paper,
      we describe an automatic method for finding neurons in sequences of 2D sections.
      The proposed method formulates the problem of finding paths through sets of
      sections as an optimal path computation, which applies a cost function to the
      identification of a cell from one section to the next and solves this
      optimization problem using Dijkstra's algorithm. This basic formulation allows us
      to account for variability or inconsistencies between sections and to prioritize
      cells based on the evidence of their connectivity.

PMID- 19172171
TI  - Field validity and feasibility of four techniques for the detection of Trichuris
      in simians: a model for monitoring drug efficacy in public health?
AB  - BACKGROUND: Soil-transmitted helminths, such as Trichuris trichiura, are of major
      concern in public health. Current efforts to control these helminth infections
      involve periodic mass treatment in endemic areas. Since these large-scale
      interventions are likely to intensify, monitoring the drug efficacy will become
      indispensible. However, studies comparing detection techniques based on
      sensitivity, fecal egg counts (FEC), feasibility for mass diagnosis and drug
      efficacy estimates are scarce. METHODOLOGY/PRINCIPAL FINDINGS: In the present
      study, the ether-based concentration, the Parasep Solvent Free (SF), the McMaster
      and the FLOTAC techniques were compared based on both validity and feasibility
      for the detection of Trichuris eggs in 100 fecal samples of nonhuman primates. In
      addition, the drug efficacy estimates of quantitative techniques was examined
      using a statistical simulation. Trichuris eggs were found in 47% of the samples.
      FLOTAC was the most sensitive technique (100%), followed by the Parasep SF (83.0%
      [95% confidence interval (CI): 82.4-83.6%]) and the ether-based concentration
      technique (76.6% [95% CI: 75.8-77.3%]). McMaster was the least sensitive (61.7%
      [95% CI: 60.7-62.6%]) and failed to detect low FEC. The quantitative comparison
      revealed a positive correlation between the four techniques (Rs = 0.85-0.93;
      p<0.0001). However, the ether-based concentration technique and the Parasep SF
      detected significantly fewer eggs than both the McMaster and the FLOTAC
      (p<0.0083). Overall, the McMaster was the most feasible technique (3.9 min/sample
      for preparing, reading and cleaning of the apparatus), followed by the ether
      based concentration technique (7.7 min/sample) and the FLOTAC (9.8 min/sample).
      Parasep SF was the least feasible (17.7 min/sample). The simulation revealed that
      the sensitivity is less important for monitoring drug efficacy and that both
      FLOTAC and McMaster were reliable estimators. CONCLUSIONS/SIGNIFICANCE: The
      results of this study demonstrated that McMaster is a promising technique when
      making use of FEC to monitor drug efficacy in Trichuris.

PMID- 19172172
TI  - The importance of pH in regulating the function of the Fasciola hepatica
      cathepsin L1 cysteine protease.
AB  - The helminth parasite Fasciola hepatica secretes cathepsin L cysteine proteases
      to invade its host, migrate through tissues and digest haemoglobin, its main
      source of amino acids. Here we investigated the importance of pH in regulating
      the activity and functions of the major cathepsin L protease FheCL1. The slightly
      acidic pH of the parasite gut facilitates the auto-catalytic activation of FheCL1
      from its inactive proFheCL1 zymogen; this process was approximately 40-fold
      faster at pH 4.5 than at pH 7.0. Active mature FheCL1 is very stable at acidic
      and neutral conditions (the enzyme retained approximately 45% activity when
      incubated at 37 degrees C and pH 4.5 for 10 days) and displayed a broad pH range
      for activity peptide substrates and the protein ovalbumin, peaking between pH 5.5
      and pH 7.0. This pH profile likely reflects the need for FheCL1 to function both
      in the parasite gut and in the host tissues. FheCL1, however, could not cleave
      its natural substrate Hb in the pH range pH 5.5 and pH 7.0; digestion occurred
      only at pH</=4.5, which coincided with pH-induced dissociation of the Hb
      tetramer. Our studies indicate that the acidic pH of the parasite relaxes the Hb
      structure, making it susceptible to proteolysis by FheCL1. This process is
      enhanced by glutathione (GSH), the main reducing agent contained in red blood
      cells. Using mass spectrometry, we show that FheCL1 can degrade Hb to small
      peptides, predominantly of 4-14 residues, but cannot release free amino acids.
      Therefore, we suggest that Hb degradation is not completed in the gut lumen but
      that the resulting peptides are absorbed by the gut epithelial cells for further
      processing by intracellular di- and amino-peptidases to free amino acids that are
      distributed through the parasite tissue for protein anabolism.

PMID- 19172173
TI  - Compound evolutionary history of the rhesus macaque MHC class I B region revealed
      by microsatellite analysis and localization of retroviral sequences.
AB  - In humans, the single polymorphic B locus of the major histocompatibility complex
      is linked to the microsatellite MIB. In rhesus macaques, however, haplotypes are
      characterized by the presence of unique combinations of multiple B genes, which
      may display different levels of polymorphism. The aim of the study was to shed
      light on the evolutionary history of this highly complex region. First, the
      robustness of the microsatellite MIB-linked to almost half of the B genes in
      rhesus macaques (Mamu-B)-for accurate B haplotyping was studied. Based on the
      physical map of an established haplotype comprising 7 MIB loci, each located next
      to a certain Mamu-B gene, two MIB loci, MIB1 and MIB6, were investigated in a
      panel of MHC homozygous monkeys. MIB1 revealed a complex genotyping pattern,
      whereas MIB6 analysis resulted in the detection of one or no amplicon. Both
      patterns are specific for a given B haplotype, show Mendelian segregation, and
      even allow a more precise haplotype definition than do traditional typing
      methods. Second, a search was performed for retroelements that may have played a
      role in duplication processes as observed in the macaque B region. This resulted
      in the description of two types of duplicons. One basic unit comprises an
      expressed Mamu-B gene, adjacent to an HERV16 copy closely linked to MIB. The
      second type of duplicon comprises a Mamu-B (pseudo)gene, linked to a truncated
      HERV16 structure lacking its MIB segment. Such truncation seems to coincide with
      the loss of B gene transcription. Subsequent to the duplication processes,
      recombination between MIB and Mamu-B loci appears to have occurred, resulting in
      a hyperplastic B region. Thus, analysis of MIB in addition to B loci allows
      deciphering of the compound evolutionary history of the class I B region in Old
      World monkeys.

PMID- 19172174
TI  - Accurate inference of subtle population structure (and other genetic
      discontinuities) using principal coordinates.
AB  - BACKGROUND: Accurate inference of genetic discontinuities between populations is
      an essential component of intraspecific biodiversity and evolution studies, as
      well as associative genetics. The most widely-used methods to infer population
      structure are model-based, Bayesian MCMC procedures that minimize Hardy-Weinberg
      and linkage disequilibrium within subpopulations. These methods are useful, but
      suffer from large computational requirements and a dependence on modeling
      assumptions that may not be met in real data sets. Here we describe the
      development of a new approach, PCO-MC, which couples principal coordinate
      analysis to a clustering procedure for the inference of population structure from
      multilocus genotype data. METHODOLOGY/PRINCIPAL FINDINGS: PCO-MC uses data from
      all principal coordinate axes simultaneously to calculate a multidimensional
      "density landscape", from which the number of subpopulations, and the membership
      within subpopulations, is determined using a valley-seeking algorithm. Using
      extensive simulations, we show that this approach outperforms a Bayesian MCMC
      procedure when many loci (e.g. 100) are sampled, but that the Bayesian procedure
      is marginally superior with few loci (e.g. 10). When presented with sufficient
      data, PCO-MC accurately delineated subpopulations with population F(st) values as
      low as 0.03 (G'(st)>0.2), whereas the limit of resolution of the Bayesian
      approach was F(st) = 0.05 (G'(st)>0.35). CONCLUSIONS/SIGNIFICANCE: We draw a
      distinction between population structure inference for describing biodiversity as
      opposed to Type I error control in associative genetics. We suggest that discrete
      assignments, like those produced by PCO-MC, are appropriate for circumscribing
      units of biodiversity whereas expression of population structure as a continuous
      variable is more useful for case-control correction in structured association
      studies.

PMID- 19172175
TI  - Carcinogenic effects in a phenylketonuria mouse model.
AB  - Phenylketonuria (PKU) is a metabolic disorder caused by impaired phenylalanine
      hydroxylase (PAH). This condition results in hyperphenylalaninemia and elevated
      levels of abnormal phenylalanine metabolites, among which is phenylacetic
      acid/phenylacetate (PA). In recent years, PA and its analogs were found to have
      anticancer activity against a variety of malignancies suggesting the possibility
      that PKU may offer protection against cancer through chronically elevated levels
      of PA. We tested this hypothesis in a genetic mouse model of PKU (PAH(enu2))
      which has a biochemical profile that closely resembles that of human PKU. Plasma
      levels of phenylalanine in homozygous (HMZ) PAH(enu2) mice were >12-fold those of
      heterozygous (HTZ) littermates while tyrosine levels were reduced. Phenylketones,
      including PA, were also markedly elevated to the range seen in the human disease.
      Mice were subjected to 7,12 dimethylbenz[a]anthracene (DMBA) carcinogenesis, a
      model which is sensitive to the anticancer effects of the PA derivative 4
      chlorophenylacetate (4-CPA). Tumor induction by DMBA was not significantly
      different between the HTZ and HMZ mice, either in total tumor development or in
      the type of cancers that arose. HMZ mice were then treated with 4-CPA as positive
      controls for the anticancer effects of PA and to evaluate its possible effects on
      phenylalanine metabolism in PKU mice. 4-CPA had no effect on the plasma
      concentrations of phenylalanine, phenylketones, or tyrosine. Surprisingly, the
      HMZ mice treated with 4-CPA developed an unexplained neuromuscular syndrome which
      precluded its use in these animals as an anticancer agent. Together, these
      studies support the use of PAH(enu2) mice as a model for studying human PKU.
      Chronically elevated levels of PA in the PAH(enu2) mice were not protective
      against cancer.

PMID- 19172176
TI  - Waging peace through neglected tropical disease control: a US foreign policy for
      the bottom billion.

PMID- 19172177
TI  - Evidence-based policy on deworming.

PMID- 19172178
TI  - Taenia solium cysticercosis hotspots surrounding tapeworm carriers: clustering on
      human seroprevalence but not on seizures.
AB  - BACKGROUND: Neurocysticercosis accounts for 30%-50% of all late-onset epilepsy in
      endemic countries. We assessed the clustering patterns of Taenia solium human
      cysticercosis seropositivity and seizures around tapeworm carriers in seven rural
      communities in Peru. METHODOLOGY: The presence of T. solium-specific antibodies
      was defined as one or more positive bands in the enzyme-linked
      immunoelectrotransfer blot (EITB). Neurocysticercosis-related seizures cases were
      diagnosed clinically and had positive neuroimaging or EITB. PRINCIPAL FINDINGS:
      Eleven tapeworm carriers were identified by stool microscopy. The seroprevalence
      of human cysticercosis was 24% (196/803). Seroprevalence was 21% >50 m from a
      carrier and increased to 32% at 1-50 m (p = 0.047), and from that distance
      seroprevalence had another significant increase to 64% at the homes of carriers
      (p = 0.004). Seizure prevalence was 3.0% (25/837) but there were no differences
      between any pair of distance ranges (p = 0.629, Wald test 2 degrees of freedom).
      CONCLUSION/SIGNIFICANCE: We observed a significant human cysticercosis
      seroprevalence gradient surrounding current tapeworm carriers, although
      cysticercosis-related seizures did not cluster around carriers. Due to
      differences in the timing of the two outcomes, seroprevalence may reflect recent
      T. solium exposure more accurately than seizure frequency.

PMID- 19172179
TI  - The ubiquitin ligase RPM-1 and the p38 MAPK PMK-3 regulate AMPA receptor
      trafficking.
AB  - Ubiquitination occurs at synapses, yet its role remains unclear. Previous studies
      demonstrated that the RPM-1 ubiquitin ligase organizes presynaptic boutons at
      neuromuscular junctions in C. elegans motorneurons. Here we find that RPM-1 has a
      novel postsynaptic role in interneurons, where it regulates the trafficking of
      the AMPA-type glutamate receptor GLR-1 from synapses into endosomes. Mutations in
      rpm-1 cause the aberrant accumulation of GLR-1 in neurites. Moreover, rpm-1
      mutations enhance the endosomal accumulation of GLR-1 observed in mutants for lin
      10, a Mint2 ortholog that promotes GLR-1 recycling from Syntaxin-13 containing
      endosomes. As in motorneurons, RPM-1 negatively regulates the pmk-3/p38 MAPK
      pathway in interneurons by repressing the protein levels of the MAPKKK DLK-1.
      This regulation of PMK-3 signaling is critical for RPM-1 function with respect to
      GLR-1 trafficking, as pmk-3 mutations suppress both lin-10 and rpm-1 mutations.
      Positive or negative changes in endocytosis mimic the effects of rpm-1 or pmk-3
      mutations, respectively, on GLR-1 trafficking. Specifically, RAB-5(GDP), an
      inactive mutant of RAB-5 that reduces endocytosis, mimics the effect of pmk-3
      mutations when introduced into wild-type animals, and occludes the effect of pmk
      3 mutations when introduced into pmk-3 mutants. By contrast, RAB-5(GTP), which
      increases endocytosis, suppresses the effect of pmk-3 mutations, mimics the
      effect of rpm-1 mutations, and occludes the effect of rpm-1 mutations. Our
      findings indicate a novel specialized role for RPM-1 and PMK-3/p38 MAPK in
      regulating the endosomal trafficking of AMPARs at central synapses.

PMID- 19172180
TI  - Requirement for abasic endonuclease gene homologues in Arabidopsis seed
      development.
AB  - Arabidopsis thaliana has three genes, Ape1L, Ape2, and Arp, that show homology to
      abasic (apurinic/apyrimidinic) endonuclease genes of bacterial, yeast, or animal
      cells. In bacteria, yeast, and animals, abasic endonucleases function in base
      excision repair of oxidized and other modified DNA bases. Here we report that
      plants with knock-out mutations in any one of Ape1L, Ape2, or Arp show no
      apparent differences from wild type in growth rate, growth habit, and fertility.
      However, coincident knock-out mutations in Ape1L and Ape2 are lethal and lead to
      abortion of developing embryos. Mutations of Arp are not deleterious, even in
      combination with one of the other two mutations. The results are consistent with
      the interpretation that the process of base excision repair, involving at least
      one intact copy of Ape1L or Ape2, is required in the process of embryogenesis.

PMID- 19172181
TI  - Loss of magel2, a candidate gene for features of Prader-Willi syndrome, impairs
      reproductive function in mice.
AB  - BACKGROUND: MAGEL2 is one of several genes typically inactivated in the
      developmental obesity disorder Prader-Willi syndrome (PWS). The physiological
      consequences of loss of MAGEL2, but without the concurrent loss of other PWS
      genes, are not well understood. Gene-targeted mutation of Magel2 in mice disrupts
      circadian rhythm and metabolism causing reduced total activity, reduced weight
      gain before weaning, and increased adiposity after weaning. PRINCIPAL FINDINGS:
      We now show that loss of Magel2 in mice causes reduced fertility in both males
      and females through extended breeding intervals and early reproductive decline
      and termination. Female Magel2-null mice display extended and irregular estrous
      cycles, while males show decreased testosterone levels, and reduced olfactory
      preference for female odors. CONCLUSIONS: Our results suggest that loss of MAGEL2
      contributes to the reproductive deficits seen in people with PWS, and further
      highlights the role of normal circadian rhythm in the maintenance of fertility.

PMID- 19172182
TI  - Mast cells and gastrointestinal dysmotility in the cystic fibrosis mouse.
AB  - BACKGROUND: Cystic fibrosis (CF) has many effects on the gastrointestinal tract
      and a common problem in this disease is poor nutrition. In the CF mouse there is
      an innate immune response with a large influx of mast cells into the muscularis
      externa of the small intestine and gastrointestinal dysmotility. The aim of this
      study was to evaluate the potential role of mast cells in gastrointestinal
      dysmotility using the CF mouse (Cftr(tm1UNC), Cftr knockout). METHODOLOGY: Wild
      type (WT) and CF mice were treated for 3 weeks with mast cell stabilizing drugs
      (ketotifen, cromolyn, doxantrazole) or were treated acutely with a mast cell
      activator (compound 48/80). Gastrointestinal transit was measured using gavage of
      a fluorescent tracer. RESULTS: In CF mice gastric emptying at 20 min post-gavage
      did not differ from WT, but was significantly less than in WT at 90 min post
      gavage. Gastric emptying was significantly increased in WT mice by doxantrazole,
      but none of the mast cell stabilizers had any significant effect on gastric
      emptying in CF mice. Mast cell activation significantly enhanced gastric emptying
      in WT mice but not in CF mice. Small intestinal transit was significantly less in
      CF mice as compared to WT. Of the mast cell stabilizers, only doxantrazole
      significantly affected small intestinal transit in WT mice and none had any
      effect in CF mice. Mast cell activation resulted in a small but significant
      increase in small intestinal transit in CF mice but not WT mice. CONCLUSIONS: The
      results indicate that mast cells are not involved in gastrointestinal dysmotility
      but their activation can stimulate small intestinal transit in cystic fibrosis.

PMID- 19172183
TI  - Does deworming improve growth and school performance in children?

PMID- 19172184
TI  - Geohelminth Infections among pregnant women in rural western Kenya; a cross
      sectional study.
AB  - BACKGROUND: Geohelminth infections are common in rural western Kenya, but risk
      factors and effects among pregnant women are not clear. METHODOLOGY: During a
      community-based cross-sectional survey, pregnant women were interviewed and asked
      to provide a blood sample and a single fecal sample. Hemoglobin was measured and
      a blood slide examined for malaria. Geohelminth infections were identified using
      the concentration and Kato-Katz method. RESULTS: Among 390 participants who
      provided a stool sample, 76.2% were infected with at least one geohelminth: 52.3%
      with Ascaris lumbricoides, 39.5% with hookworm, and 29.0% with Trichuris
      trichiura. Infection with at least one geohelminth species was associated with
      the use of an unprotected water source (adjusted odds ratio [AOR] 1.8, 95%
      confidence interval [CI] 1.1-3.0) and the lack of treatment of drinking water
      (AOR 1.8, 95% CI 1.1-3.1). Geohelminth infections were not associated with
      clinical symptoms, or low body mass index. A hookworm infection was associated
      with a lower mid upper arm circumference (adjusted mean decrease 0.7 cm, 95% CI
      0.3-1.2 cm). Hookworm infections with an egg count > or =1000/gram feces (11
      women) were associated with lower hemoglobin (adjusted mean decrease 1.5 g/dl,
      95% CI 0.3-2.7). Among gravidae 2 and 3, women with A. lumbricoides were less
      likely to have malaria parasitemia (OR 0.4, 95% CI 0.2-0.8) compared to women
      without A. lumbricoides, unlike other gravidity groups. CONCLUSION: Geohelminth
      infections are common in this pregnant population; however, there were few
      observed detrimental effects. Routine provision of antihelminth treatment during
      an antenatal clinic visit is recommended, but in this area an evaluation of the
      impact on pregnancy, malaria, and birth outcome is useful.

PMID- 19172185
TI  - Graded Smad2/3 activation is converted directly into levels of target gene
      expression in embryonic stem cells.
AB  - The Transforming Growth Factor (TGF) beta signalling family includes morphogens,
      such as Nodal and Activin, with important functions in vertebrate development.
      The concentration of the morphogen is critical for fate decisions in the
      responding cells. Smad2 and Smad3 are effectors of the Nodal/Activin branch of
      TGFbeta signalling: they are activated by receptors, enter the nucleus and
      directly transcribe target genes. However, there have been no studies correlating
      levels of Smad2/3 activation with expression patterns of endogenous target genes
      in a developmental context over time. We used mouse Embryonic Stem (ES) cells to
      create a system whereby levels of activated Smad2/3 can be manipulated by an
      inducible constitutively active receptor (Alk4*) and an inhibitor (SB-431542)
      that blocks specifically Smad2/3 activation. The transcriptional responses were
      analysed by microarrays at different time points during activation and
      repression. We identified several genes that follow faithfully and reproducibly
      the Smad2/3 activation profile. Twenty-seven of these were novel and expressed in
      the early embryo downstream of Smad2/3 signalling. As they responded to Smad2/3
      activation in the absence of protein synthesis, they were considered direct.
      These immediate responsive genes included negative intracellular feedback
      factors, like SnoN and I-Smad7, which inhibit the transcriptional activity of
      Smad2/3. However, their activation did not lead to subsequent repression of
      target genes over time, suggesting that this type of feedback is inefficient in
      ES cells or it is counteracted by mechanisms such as ubiquitin-mediated
      degradation by Arkadia. Here we present an ES cell system along with a database
      containing the expression profile of thousands of genes downstream of Smad2/3
      activation patterns, in the presence or absence of protein synthesis.
      Furthermore, we identify primary target genes that follow proportionately and
      with high sensitivity changes in Smad2/3 levels over 15-30 hours. The above
      system and resource provide tools to study morphogen function in development.

PMID- 19172186
TI  - Deworming and development: asking the right questions, asking the questions
      right.

PMID- 19172187
TI  - Molecular and behavioral differentiation among Brazilian populations of Lutzomyia
      longipalpis (Diptera: Psychodidae: Phlebotominae).
AB  - BACKGROUND: Lutzomyia longipalpis is the primary vector of American visceral
      leishmaniasis. There is strong evidence that L. longipalpis is a species complex,
      but until recently the existence of sibling species among Brazilian populations
      was considered a controversial issue. In addition, there is still no consensus
      regarding the number of species occurring in this complex. METHODOLOGY/PRINCIPAL
      FINDINGS: Using period, a gene that controls circadian rhythms and affects
      interpulse interval periodicity of the male courtship songs in Drosophila
      melanogaster and close relatives, we analyzed the molecular polymorphism in a
      number of L. longipalpis samples from different regions in Brazil and compared
      the results with our previously published data using the same marker. We also
      studied the male copulation songs and pheromones from some of these populations.
      The results obtained so far suggest the existence of two main groups of
      populations in Brazil, one group representing a single species with males
      producing Burst-type copulation songs and cembrene-1 pheromones; and a second
      group that is more heterogeneous and probably represents a number of incipient
      species producing different combinations of Pulse-type songs and pheromones.
      CONCLUSIONS/SIGNIFICANCE: Our results reveal a high level of complexity in the
      divergence and gene-flow among Brazilian populations of the L. longipalpis
      species complex. This raises important questions concerning the epidemiological
      consequences of this incipient speciation process.

PMID- 19172188
TI  - Methionine sulfoxides on prion protein Helix-3 switch on the alpha-fold
      destabilization required for conversion.
AB  - BACKGROUND: The conversion of the cellular prion protein (PrP(C)) into the
      infectious form (PrP(Sc)) is the key event in prion induced neurodegenerations.
      This process is believed to involve a multi-step conformational transition from
      an alpha-helical (PrP(C)) form to a beta-sheet-rich (PrP(Sc)) state. In addition
      to the conformational difference, PrP(Sc) exhibits as covalent signature the
      sulfoxidation of M213. To investigate whether such modification may play a role
      in the misfolding process we have studied the impact of methionine oxidation on
      the dynamics and energetics of the HuPrP(125-229) alpha-fold.
      METHODOLOGY/PRINCIPAL FINDINGS: Using molecular dynamics simulation, essential
      dynamics, correlated motions and signal propagation analysis, we have found that
      substitution of the sulfur atom of M213 by a sulfoxide group impacts on the
      stability of the native state increasing the flexibility of regions preceding the
      site of the modification and perturbing the network of stabilizing interactions.
      Together, these changes favor the population of alternative states which maybe
      essential in the productive pathway of the pathogenic conversion. These changes
      are also observed when the sulfoxidation is placed at M206 and at both, M206 and
      M213. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the sulfoxidation of
      Helix-3 methionines might be the switch for triggering the initial alpha-fold
      destabilization required for the productive pathogenic conversion.

PMID- 19172189
TI  - Split-cre complementation indicates coincident activity of different genes in
      vivo.
AB  - Cre/LoxP recombination is the gold standard for conditional gene regulation in
      mice in vivo. However, promoters driving the expression of Cre recombinase are
      often active in a wide range of cell types and therefore unsuited to target more
      specific subsets of cells. To overcome this limitation, we designed inactive
      "split-Cre" fragments that regain Cre activity when overlapping co-expression is
      controlled by two different promoters. Using transgenic mice and virus-mediated
      expression of split-Cre, we show that efficient reporter gene activation is
      achieved in vivo. In the brain of transgenic mice, we genetically defined a
      subgroup of glial progenitor cells in which the Plp1- and the Gfap-promoter are
      simultaneously active, giving rise to both astrocytes and NG2-positive glia.
      Similarly, a subset of interneurons was labelled after viral transfection using
      Gad67- and Cck1 promoters to express split-Cre. Thus, split-Cre mediated genomic
      recombination constitutes a powerful spatial and temporal coincidence detector
      for in vivo targeting.

PMID- 19172190
TI  - Naloxone's pentapeptide binding site on filamin A blocks Mu opioid receptor-Gs
      coupling and CREB activation of acute morphine.
AB  - Chronic morphine causes the mu opioid receptor (MOR) to switch its coupling from
      Gi/o to Gs, resulting in excitatory signaling via both Galphas and its Gbetagamma
      dimer. Ultra-low-dose naloxone (NLX) prevents this switch and attenuates opioid
      tolerance and dependence. This protective effect is mediated via a high-affinity
      interaction of NLX to a pentapeptide region in c-terminal filamin A (FLNA), a
      scaffolding protein interacting with MOR. In organotypic striatal slice cultures,
      we now show that acute morphine induces a dose-dependent Go-to-Gs coupling switch
      at 5 and 15 min that resolves by 1 hr. The acute Gs coupling induced by 100
      microM morphine was completely prevented by co-treatment with 100 pM NLX, (+)NLX,
      or naltrexone (NTX), or their pentapeptide binding site (FLNA(2561-2565)), which
      we show can act as a decoy for MOR or bind to FLNA itself. All of these co
      treatments presumably prevent the MOR-FLNA interaction. Since ultra-low-dose NTX
      also attenuates the addictive properties of opioids, we assessed striatal cAMP
      production and CREB phosphorylation at S(133). Correlating with the Gs coupling,
      acute morphine induced elevated cAMP levels and a several-fold increase in
      pS(133)CREB that were also completely blocked by NLX, NTX or the FLNA
      pentapeptide. We propose that acute, robust stimulation of MOR causes an
      interaction with FLNA that allows an initially transient MOR-Gs coupling, which
      recovers with receptor recycling but persists when MOR stimulation is repeated or
      prolonged. The complete prevention of this acute, morphine-induced MOR-Gs
      coupling by 100 pM NLX/NTX or 10 microM pentapeptide segment of FLNA further
      elucidates both MOR signaling and the mechanism of action of ultra-low-dose NLX
      or NTX in attenuating opioid tolerance, dependence and addictive potential.

PMID- 19172191
TI  - Expression of activated PIK3CA in ovarian surface epithelium results in
      hyperplasia but not tumor formation.
AB  - BACKGROUND: The Phosphatidylinositol 3'-kinase is a key regulator in various
      cancer-associated signal transduction pathways. Genetic alterations of its
      catalytic subunit alpha, PIK3CA, have been identified in ovarian cancer. Our in
      vivo data suggests that PIK3CA activation is one of the early genetic events in
      ovarian cancer. However, its role in malignant transformation of ovarian surface
      epithelium (OSE) is largely unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using the
      Mullerian inhibiting substance type II receptor (MISIIR) promoter, we generated
      transgenic mice that expressed activated PIK3CA in the Mullerian epithelium.
      Overexpression of PIK3CA in OSE induced remarkable hyperplasia, but was not able
      to malignantly transform OSE in vivo. The consistent result was also observed in
      primary cultured OSEs. Although enforced expression of PIK3CA could not induce
      OSE anchorage-independent growth, it significantly increased anchorage
      independent growth of OSE transformed by mutant K-ras. CONCLUSIONS/SIGNIFICANCE:
      While PIK3CA activation may not be able to initiate OSE transformation, we
      conclude that activation of PIK3CA may be an important molecular event
      contributing to the maintenance of OSE transformation initiated by oncogenes such
      as K-ras.

PMID- 19172192
TI  - Anticancer alkaloid lamellarins inhibit protein kinases.
AB  - Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from
      marine invertebrates, display promising anti-tumor activity. They induce
      apoptotic cell death through multi-target mechanisms, including inhibition of
      topoisomerase I, interaction with DNA and direct effects on mitochondria. We here
      report that lamellarins inhibit several protein kinases relevant to cancer such
      as cyclin-dependent kinases, dual-specificity tyrosine phosphorylation activated
      kinase 1A, casein kinase 1, glycogen synthase kinase-3 and PIM-1. A good
      correlation is observed between the effects of lamellarins on protein kinases and
      their action on cell death, suggesting that inhibition of specific kinases may
      contribute to the cytotoxicity of lamellarins. Structure/activity relationship
      suggests several paths for the optimization of lamellarins as kinase inhibitors.

PMID- 19172193
TI  - Characterizing the anti-HIV activity of papuamide A.
AB  - Papuamide A is representative of a class of marine derived cyclic depsipeptides,
      reported to have cytoprotective activity against HIV-1 in vitro. We show here
      that papuamide A acts as an entry inhibitor, preventing human immunodeficiency
      virus infection of host cells and that this inhibition is not specific to R5 or
      X4 tropic virus. This inhibition of viral entry was determined to not be due to
      papuamide A binding to CD4 or HIV gp120, the two proteins involved in the cell
      virus recognition and binding. Furthermore, papuamide A was able to inhibit HIV
      pseudotype viruses expressing envelope glycoproteins from vesicular stomatitis
      virus or amphotropic murine leukemia virus indicating the mechanism of viral
      entry inhibition is not HIV-1 envelope glycoprotein specific. Time delayed
      addition studies with the pseudotyped viruses show that papuamide A inhibits
      viral infection only at the initial stage of the viral life cycle. Additionally,
      pretreatment studies revealed that the virus, and not the cell, is the target of
      papuamide A's action. Together, these results suggest a direct virucidal
      mechanism of HIV-1 inhibition by papuamide A. We also demonstrate here that the
      other papuamides (B-D) are able to inhibit viral entry indicating that the free
      amino moiety of 2,3-diaminobutanoic acid residue is not required for the
      virucidal activity.

PMID- 19172194
TI  - A tropical marine microbial natural products geobibliography as an example of
      desktop exploration of current research using web visualisation tools.
AB  - Microbial marine biodiscovery is a recent scientific endeavour developing at a
      time when information and other technologies are also undergoing great technical
      strides. Global visualisation of datasets is now becoming available to the world
      through powerful and readily available software such as Worldwind, ArcGIS
      Explorer and Google Earth. Overlaying custom information upon these tools is
      within the hands of every scientist and more and more scientific organisations
      are making data available that can also be integrated into these global
      visualisation tools. The integrated global view that these tools enable provides
      a powerful desktop exploration tool. Here we demonstrate the value of this
      approach to marine microbial biodiscovery by developing a geobibliography that
      incorporates citations on tropical and near-tropical marine microbial natural
      products research with Google Earth and additional ancillary global data sets.
      The tools and software used are all readily available and the reader is able to
      use and install the material described in this article.

PMID- 19172195
TI  - Acetylcholinesterase-inhibiting activity of pyrrole derivatives from a novel
      marine gliding bacterium, Rapidithrix thailandica.
AB  - Acetylcholinesterase-inhibiting activity of marinoquinoline A (1), a new
      pyrroloquinoline from a novel species of a marine gliding bacterium Rapidithrix
      thailandica, was assessed (IC(50) 4.9 microM). Two related pyrrole derivatives, 3
      (2'-aminophenyl)-pyrrole (3) and 2,2-dimethyl-pyrrolo-1,2-dihydroquinoline (4),
      were also isolated from two other strains of R. thailandica. The isolation of 3
      from a natural source is reported here for the first time. Compound 4 was
      proposed to be an isolation artifact derived from 3. The two isolated compounds
      were virtually inactive in the acetylcholinesterase-inhibitory assay (enzyme
      inhibition < 30% at 0.1 g L(-1)).

PMID- 19172196
TI  - Detection of diarrheic shellfish poisoning and azaspiracid toxins in Moroccan
      mussels: comparison of the LC-MS method with the commercial immunoassay kit.
AB  - Diarrheic shellfish poisoning (DSP) is a recurrent gastrointestinal illness in
      Morocco, resulting from consumption of contaminated shellfish. In order to
      develop a rapid and reliable technique for toxins detection, we have compared the
      results obtained by a commercial immunoassay-"DSP-Check" kit" with those obtained
      by LC-MS. Both techniques are capable of detecting the toxins in the whole flesh
      extract which was subjected to prior alkaline hydrolysis in order to detect
      simultaneously the esterified and non esterified toxin forms. The LC-MS method
      was found to be able to detect a high level of okadaic acid (OA), low level of
      dinophysistoxin-2 (DTX2), and surprisingly, traces of azaspiracids 2 (AZA2) in
      mussels. This is the first report of a survey carried out for azaspiracid (AZP)
      contamination of shellfish harvested in the coastal areas of Morocco. The "DSP
      Check" kit was found to detect quantitatively DSP toxins in all contaminated
      samples containing only OA, provided that the parent toxins were within the range
      of detection and was not in an ester form. A good correlation was observed
      between the two methods when appropriate dilutions were performed. The
      immunoassay kit appeared to be more sensitive, specific and faster than LC-MS for
      determination of DSP in total shellfish extract.

PMID- 19172197
TI  - Extracts from Cladiella australis, Clavularia viridis and Klyxum simplex (soft
      corals) are capable of inhibiting the growth of human oral squamous cell
      carcinoma cells.
AB  - Many biomedical products have already been obtained from marine organisms. In
      order to search more therapeutic drugs against cancer, this study demonstrates
      the cytotoxicity effects of Cladiella australis, Clavularia viridis and Klyxum
      simplex extracts on human oral squamous cell carcinoma (SCC4, SCC9 and SCC25)
      cells using cell adhesion and cell viability assay. The morphological alterations
      in SCCs cells after treatment with three extracts, such as typical nuclear
      condensation, nuclear fragmentation and apoptotic bodies of cells were
      demonstrated by Hoechst stain. Flow cytometry indicated that three extracts
      sensitized SCC25 cells in the G(0)/G(1) and S-G(2)/M phases with a concomitant
      significantly increased sub-G(1) fraction, indicating cell death by apoptosis.
      This apoptosis process was accompanied by activation of caspase-3 expression
      after SCC25 cells were treated with three extracts. Thereby, it is possible that
      extracts of C. australis, C. viridis and K. simplex cause apoptosis of SCCs and
      warrant further research investigating the possible anti-oral cancer compounds in
      these soft corals.

PMID- 19172198
TI  - Antioxidant activities of hydrolysates of Arca subcrenata prepared with three
      proteases.
AB  - In order to get products with antioxidant activity from Arca subcrenata Lischke,
      the optimal hydrolase and hydrolysis conditions were investigated in the paper.
      Three proteases (neutrase, alcalase and papain) were applied to hydrolyze the
      homogenate of A. subcrenata. An orthogonal design was used to optimize hydrolysis
      conditions, and the pH-stat methods was used to determine the degree of
      hydrolysis. Viewed from the angle of reducing power, such as scavenging
      activities against alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical and
      hydrogen peroxide, the antioxidant activities of the alcalase hydrolysate (AH)
      were superior to neutrase hydrolysate (NH) and papain hydrolysate (PH), and its
      EC(50) values in DPPH radical and hydrogen peroxide scavenging effect were 6.23
      mg/ml and 19.09 mg/ml, respectively. Moreover, compared with products hydrolyzed
      by neutrase and papain, the molecular mass of AH was lower and its content of
      amino acid of peptides was higher. Therefore, alcalase was selected as the
      optimal enzyme to produce active ingredients since its hydrolysate exhibited the
      best antioxidant activity among them and possessed large amount of potential
      active peptides.

PMID- 19172199
TI  - Characterization of Streptomyces spp. isolated from the sea surface microlayer in
      the Trondheim Fjord, Norway.
AB  - The water surface microlayer is still poorly explored, although it has been shown
      to contain a high density of metabolically active bacteria, often called
      bacterioneuston. Actinomycetes from the surface microlayer in the Trondheim
      fjord, Norway, have been isolated and characterized. A total of 217 isolates from
      two separate samples morphologically resembling the genus Streptomyces have been
      further investigated in this study. Antimicrobial assays showed that about 80% of
      the isolates exhibited antagonistic activity against non-filamentous fungus, Gram
      negative, and Gram-positive bacteria. Based on the macroscopic analyses and
      inhibition patterns from the antimicrobial assays, the sub-grouping of isolates
      was performed. Partial 16S rDNAs from the candidates from each subgroup were
      sequenced and phylogenetic analysis performed. 7 isolates with identical 16S rDNA
      sequences were further studied for the presence of PKS type I genes. Sequencing
      and phylogenetic analysis of the PKS gene fragments revealed that horizontal gene
      transfer between closely related species might have taken place. Identification
      of unique PKS genes in these isolates implies that de-replication can not be
      performed based solely on the 16S rDNA sequences. The results obtained in this
      study suggest that streptomycetes from the neuston population may be an
      interesting source for discovery of new antimicrobial agents.

PMID- 19172201
TI  - Advances in inflammatory bowel disease: are patients taking their medicines?
      Interview by Paul C. Adams.
AB  - Dr Subrata Ghosh is the Professor of Gastroenterology at the Imperial College,
      Hammersmith Hospital, London, England. He has bench-to-bedside research interests
      in inflammatory bowel disease (IBD) and other intestinal inflammatory diseases.
      He will become the Head of the Division of Gastroenterology at the University of
      Calgary, Calgary, Alberta, in March 2009.

PMID- 19172200
TI  - Immunomodulatory effects of domoic acid differ between in vivo and in vitro
      exposure in mice.
AB  - The immunotoxic potential of domoic acid (DA), a well-characterized neurotoxin,
      has not been fully investigated. Phagocytosis and lymphocyte proliferation were
      evaluated following in vitro and in vivo exposure to assay direct vs indirect
      effects. Mice were injected intraperitoneally with a single dose of DA (2.5
      microg/g b.w.) and sampled after 12, 24, or 48 hr. In a separate experiment,
      leukocytes and splenocytes were exposed in vitro to 0, 1, 10, or 100 microM DA.
      In vivo exposure resulted in a significant increase in monocyte phagocytosis (12
      hr), a significant decrease in neutrophil phagocytosis (24-hr), a significant
      decrease in monocyte phagocytosis (48-hr), and a significant reduction in T-cell
      mitogen-induced lymphocyte proliferation (24-hr). In vitro exposure significantly
      reduced neutrophil and monocyte phagocytosis at 1 muM. B- and T-cell mitogen
      induced lymphocyte proliferation were both significantly increased at 1 and 10
      microM, and significantly decreased at 100 microM. Differences between in vitro
      and in vivo results suggest that DA may exert its immunotoxic effects both
      directly and indirectly. Modulation of cytosolic calcium suggests that DA exerts
      its effects through ionotropic glutamate subtype surface receptors at least on
      monocytes. This study is the first to identify DA as an immunotoxic chemical in a
      mammalian species.

PMID- 19172202
TI  - Narrow band imaging for the detection of neoplastic lesions of the colon.

PMID- 19172203
TI  - Gastric intramural hematoma: a case report and literature review.
AB  - Intramural hematoma of the gastrointestinal tract is an uncommon occurrence, with
      the majority being localized to the esophagus or duodenum. Hematoma of the
      gastric wall is very rare, and has been described most commonly in association
      with coagulopathy, peptic ulcer disease, trauma, and amyloid-associated
      microaneurysms. A case of massive gastric intramural hematoma, secondary to
      anticoagulation therapy, and a gastric ulcer that was successfully managed with
      conservative therapy, is presented. A literature review of previously reported
      cases of gastric hematoma is also provided.

PMID- 19172204
TI  - Hepatocellular carcinoma with cutaneous metastases.
AB  - Two cases of cutaneous metastases from hepatocellular carcinoma (HCC) are
      reported. Both patients had been diagnosed with HCC at least one year before the
      appearance of skin lesions. The lesions presented as small reddish nodules in
      both patients, with a large additional vascular lesion in one of the patients.
      Cutaneous metastases from HCC are very rare. However, these two cases suggest
      that patients with HCC and presenting with skin nodules should have biopsies
      performed to confirm the diagnosis.

PMID- 19172205
TI  - Does onsite cytotechnology evaluation improve the accuracy of endoscopic
      ultrasound-guided fine-needle aspiration biopsy?
AB  - BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the
      preferred modality for the cytological diagnosis of various cancers. Onsite
      cytopathology interpretation is not available in most centres. OBJECTIVE: To
      assess whether the the adequacy of tissue sampling assessed by an onsite
      cytotechnologist improves the diagnostic accuracy of EUS-FNA. METHODS: The
      present study is a retrospective review of all patients undergoing solid mass EUS
      FNA between September 2005 and August 2007. Patients in group I (September 2005
      to August 2006) had cytology slides prepared by an endoscopy nurse. Patients in
      group II (September 2006 to August 2007) had cytology slides prepared, stained
      and assessed for adequacy of tissue sampling by a cytotechnologist in the
      endoscopy suite. The final cytopathological diagnosis (definitely positive,
      definitely negative or inconclusive) was compared between the two groups.
      RESULTS: A total of 49 EUS-FNA procedures were performed in 47 patients in group
      I and 60 EUS-FNA procedures in 55 patients in group II. Pancreatic masses were
      the most common target site in both groups. The total number of needle passes was
      105 in group I (mean 2.14 passes per patient; range one to five needle passes)
      and 158 in group II (mean 2.63 passes per patient; range one to four needle
      passes). The difference in the number of needle passes was not statistically
      significant between groups. The final diagnosis was definite in 53% in group I
      compared with 77% in group II (P=0.01). The percentage of inconclusive diagnoses
      was 47% in group I and 23% in group II (P=0.001). CONCLUSION: Onsite
      cytotechnologist interpretation of adequacy of tissue sampling significantly
      improves the diagnostic yield of EUS-FNA. This appears to be independent of the
      total number of needle passes undertaken for tissue sampling.

PMID- 19172206
TI  - Sociocultural factors that potentially affect the institution of prevention and
      treatment strategies for prevention of hepatitis B in Chinese Canadians.
AB  - BACKGROUND: Despite the availability of screening for chronic hepatitis B (CHB)
      infection and effective treatments now available, many at-risk individuals fail
      to seek appropriate medical attention. OBJECTIVE: To identify the barriers to
      care for CHB infection in a Chinese Canadian community. METHODS: A survey
      conducted in English or Chinese collected information from individuals with CHB
      infection that evaluated the level of understanding and identified the barriers
      that may prevent Chinese patients from undergoing monitoring, screening and/or
      treatment for CHB infection. RESULTS: Among the 204 patients enrolled, common
      misconceptions were that sharing food transmits hepatitis B and that patients
      with severe disease are always symptomatic. Patients with a better understanding
      of hepatitis B were better educated, younger and were being followed at a
      tertiary care centre (P<0.01 for all). Prominent barriers to health care were
      time, inconvenience and language difficulties. Patients under the care of family
      physicians who had extended office hours were less likely to cite time (P=0.06)
      and distance (P=0.05) as barriers. CONCLUSION: Patient misconceptions that severe
      liver disease due to hepatitis B infection is symptomatic may factor into the
      unwillingness to spare the time and undergo the inconvenience associated with
      regular medical follow-up. Implementation of programs that increase awareness of
      the silent progression of CHB infection and provide culturally responsive
      clinics, better able to work within patients' time constraints may improve
      Chinese patients' access to health care.

PMID- 19172207
TI  - Do patients undergo prostate examination while having a colonoscopy?
AB  - OBJECTIVES: To determine the rate at which physicians report performing a digital
      rectal examination and comment on the prostate gland before performing
      colonoscopy in men 50 to 70 years of age. METHODS: A retrospective chart review
      of all men 50 to 70 years of age who had a colonoscopy in Kingston, Ontario, in
      2005 was completed. It was noted whether each physician described performing a
      digital rectal examination before the colonoscopy, and if so, whether he or she
      commented on the prostate. RESULTS: In 2005, 846 eligible colonoscopies were
      performed by 17 physicians in Kingston, Ontario. In 29.2% of cases, the physician
      made no comment about having performed a digital rectal examination; in 55.8% of
      cases, the physician commented on having completed a digital rectal examination
      but said nothing about the prostate; and in 15.0% of cases, the physician made a
      comment regarding the prostate. No physician consistently commented on the
      prostate for all patients, and in no circumstances was direct referral to another
      physician or follow-up suggested. DISCUSSION: A colonoscopy presents an ideal
      opportunity for physicians to use a digital rectal examination to assess for
      prostate cancer. Physicians performing colonoscopies in men 50 to 70 years of age
      should pay special attention to the prostate while performing a digital rectal
      examination before colonoscopy. This novel concept may help maximize resources
      for cancer screening and could potentially increase the detection rate of
      clinically palpable prostate cancer.

PMID- 19172208
TI  - The quality of screening colonoscopies in an office-based endoscopy clinic.
AB  - BACKGROUND: Wait times for hospital screening colonoscopy have increased
      dramatically in recent years, resulting in an increase in patient referrals to
      office-based endoscopy clinics. There is no formal regulation of office
      endoscopy, and it has been suggested that the quality of service in some office
      locations may be inferior to hospital procedures. OBJECTIVE: To compare the
      quality of office-based screening colonoscopies at a clinic in Oakville, Ontario,
      with published benchmarks for cecal intubation, withdrawal times, polyp
      detection, adenoma detection, cancer detection and patient complications.
      METHODS: Demographic information on consecutive patients and colonoscopy reports
      by all nine gastroenterologists at the Oakville Endoscopy Centre between August
      2006 and December 2007 were prospectively obtained. RESULTS: A total of 3741
      colonoscopies were analyzed. The mean age of patients was 57.1 years and 51.9%
      were women. The cecal intubation rate was 98.98% with an average withdrawal time
      of 9.75 min. A total of 3857 polyps were retrieved from 1725 patients (46.11%),
      and 1721 adenomas were detected in 953 patients (25.47%). A total of 126 patients
      (3.37%) had advanced polyps and 18 (0.48%) were diagnosed with colon cancer. One
      patient (0.027%) had a colonic perforation and two patients had postpolypectomy
      bleeding (0.053%). These results meet or exceed published benchmarks for quality
      colonoscopy. CONCLUSIONS: The Ontario Endoscopy Centre data demonstrate that
      office-based colonoscopies, performed by well-trained physicians using adequate
      sedation and hospital-grade equipment, result in outcomes at least equal to or
      better than those of published academic/community hospital practices and are
      therefore a viable option for the future of screening colonoscopy in Canada.

PMID- 19172209
TI  - Inflammatory bowel disease and pregnancy: evidence, uncertainty and patient
      decision-making.
AB  - Inflammatory bowel disease (IBD) often affects women during their child-bearing
      years. Management of a pregnant IBD patient, or a patient contemplating
      pregnancy, poses unique challenges and can be quite daunting. Knowledge of the
      basic interplay among disease, normal host physiology and pregnancy is vital to
      managing these patients. One of the most important advances in the management of
      IBD over the past decade has been the finding that normal pregnancy outcomes can
      be achieved when a woman enters the pregnancy in remission. New insights into the
      safety of a wider spectrum of drugs in these patients has allowed for increased
      success in IBD management. The evidence supporting medical interventions
      including biological therapy such as antibodies to tumour necrosis factor agents
      is reviewed. Once the treating physician understands this complex relationship,
      management of the pregnant IBD patient can often become a rewarding experience.

PMID- 19172210
TI  - Unsuspected polymorphic metabolism of rupatadine via its primary metabolite,
      desloratadine.

PMID- 19172211
TI  - The use of bronchial challenge to diagnose asthma in preschool children.
AB  - Wheezing and respiratory symptoms are very common in preschool children, and the
      ability to diagnose asthma correctly is important. This review describes an
      approach to the diagnosis of asthma in preschool children by means of an
      inhalation bronchial challenge. The child is exposed to increasing doses of
      challenge agent until wheezing is detected at a dose below that at which normal
      subjects respond, thus indicating bronchial hyperreactivity. The technique was
      originally developed using simple stethoscope auscultation of the lungs together
      with recording of respiratory rate and oxygen saturation (by pulse oximetry).
      Extensive studies have confirmed the safety and practicability of the technique
      and the specificity for asthma when the challenge agent is adenosine 5'
      monophosphate (AMP). Subsequently, acoustic recordings have been used to detect
      and analyse breath sounds and to quantify the wheeze; these show excellent
      correlation between the clinical detection of wheeze and the wheeze rate
      (duration of wheeze/duration of recording) during bronchial challenges in
      children. Equipment is now becoming available that can perform the acoustic
      quantification of wheeze automatically and facilitate bronchial challenges in
      young children.

PMID- 19172212
TI  - Asthma patient safety incidents: national perspectives need to be informed by
      primary care reporting.

PMID- 19172213
TI  - Simultaneous laceration of external iliac artery and vein complicating anterior
      vaginal wall sling operation for stress urinary incontinence.
AB  - CASE REPORT: We report a case of simultaneous injury of right external iliac
      artery and vein by a needle carrier that was inserted from the suprapubic area
      down to the vaginal lumen during anterior vaginal wall sling procedure.
      DISCUSSION: The risk factors and measures to be taken to avoid this life
      threatening complication are discussed.

PMID- 19172214
TI  - Nerve injury during uterosacral ligament fixation: a cadaver study.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study was to identify nerve(s)
      vulnerable to entrapment during uterosacral ligament fixation (USLF), which could
      cause postoperative lower extremity pain previously described in the literature.
      METHODS: Preserved cadavers in a medical anatomy course were used. Before the
      students' pelvic dissections, a 2-0 prolene suture was placed in the middle third
      of each left uterosacral ligament visualized. The sutures were re-evaluated at
      the end of the course. RESULTS: Nine sutures remained in place after the course,
      and one entrapped a nerve. It was part of the inferior hypogastric plexus,
      included fibers from S2 and S3, and radiated to the bladder and rectum. The
      posterior femoral cutaneous nerve was lateral and posterior to this nerve.
      CONCLUSIONS: The inferior hypogastric plexus is vulnerable during USLF.
      Entrapment of S2 and S3 fibers could cause pain in their respective dermatomes
      and could be responsible for the postoperative pain previously described.

PMID- 19172215
TI  - Ablation of cathepsin k activity in the young mouse causes hypermineralization of
      long bone and growth plates.
AB  - Cathepsin K deficiency in humans causes pycnodysostosis, which is characterized
      by dwarfism and osteosclerosis. Earlier studies of 10-week-old male cathepsin K
      deficient (knockout, KO) mice showed their bones were mechanically more brittle,
      while histomorphometry showed that both osteoclasts and osteoblasts had impaired
      activity relative to the wild type (WT). Here, we report detailed mineral and
      matrix analyses of the tibia of these animals based on Fourier transform infrared
      microspectroscopy and imaging. At 10 weeks, there was significant
      hypercalcification of the calcified cartilage and cortices in the KO. Carbonate
      content was elevated in the KO calcified cartilage as well as cortical and
      cancellous bone areas. These data suggest that cathepsin K does not affect
      mineral deposition but has a significant effect on mineralized tissue remodeling.
      Since growth plate abnormalities were extensive despite reported low levels of
      cathepsin K expression in the calcified cartilage, we used a differentiating
      chick limb-bud mesenchymal cell system that mimics endochondral ossification but
      does not contain osteoclasts, to show that cathepsin K inhibition during initial
      stages of mineral deposition retards the mineralization process while general
      inhibition of cathepsins can increase mineralization. These data suggest that the
      hypercalcification of the cathepsin K-deficient growth plate is due to
      persistence of calcified cartilage and point to a role of cathepsin K in bone
      tissue development as well as skeletal remodeling.

PMID- 19172216
TI  - Molecular characterization of an endolithic microbial community in dolomite rock
      in the central Alps (Switzerland).
AB  - Endolithic microorganisms colonize the pores in exposed dolomite rocks in the
      Piora Valley in the Swiss Alps. They appear as distinct grayish-green bands about
      1-8 mm below the rock surface. Based on environmental small subunit ribosomal RNA
      gene sequences, a diverse community driven by photosynthesis has been found.
      Cyanobacteria (57 clones), especially the genus Leptolyngbya, form the functional
      basis for an endolithic community which contains a wide spectrum of so far not
      characterized species of chemotrophic Bacteria (64 clones) with mainly
      Actinobacteria, Alpha-Proteobacteria, Bacteroidetes, and Acidobacteria, as well
      as a cluster within the Chloroflexaceae. Furthermore, a cluster within the
      Crenarchaeotes (40 clones) has been detected. Although the eukaryotic diversity
      was outside the scope of the study, an amoeba (39 clones), and several green
      algae (51 clones) have been observed. We conclude that the bacterial diversity in
      this endolithic habitat, especially of chemotrophic, nonpigmented organisms, is
      considerable and that Archaea are present as well.

PMID- 19172217
TI  - Abnormal motor excitability in patients with psychogenic paresis. A TMS study.
AB  - BACKGROUND: Patients with motor conversion disorders present an inability to
      execute movements voluntarily, although central and peripheral motor pathways are
      normal. We speculated that this phenomenon could be due to an abnormal loss of
      excitatory drive on central motor areas. METHODS: The effect of motor imagery on
      motor excitability was tested in a group of eight patients with a functional
      (psychogenic) hemiparesis and in an age-matched control group (n=8) by using
      transcranial magnetic stimulation (TMS). TMS pulses were applied at rest and
      while subjects imagined a tonic index finger adduction. Amplitudes of motor
      evoked potentials (MEP) recorded from the first dorsal interosseous muscle were
      used as an indicator of motor excitability. RESULTS: Motor thresholds and MEP
      amplitudes at rest were almost identical in the patient group and the control
      group. During motor imagery, MEP amplitudes increased by 200% in healthy
      subjects. In the patient group, motor imagery of the "paretic" index finger was
      associated with a mean MEP amplitude decrease of 37% compared with the MEP size
      at rest. Motor imagery of the unaffected index finger increased MEPs by 63% which
      was significantly different both from results in the control group and the
      "paretic" side. CONCLUSIONS: We suggest that the paradoxical decrease of motor
      excitability during motor imagery is the electrophysiological correlate of a
      disturbed voluntary control in motor conversion disorder. The results further
      indicate that this abnormality is not restricted to the clinically affected body
      part.

PMID- 19172218
TI  - Patent foramen ovale closure and migraine: are we following the wrong pathway?

PMID- 19172219
TI  - Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin
      with a moderate increase of bone turnover in postmenopausal osteoporosis: a
      randomized prospective study.
AB  - The effect of vitamin K(2) (menatetrenone) on bone turnover was investigated in
      postmenopausal patients with osteoporosis. A 6-month open-label, randomized
      prospective study was conducted in 109 patients. The control group (n = 53)
      received calcium aspartate (133.8 mg of elemental calcium daily), while the
      menatetrenone group (n = 56) received 45 mg of menatetrenone daily for 6 months.
      Serum and urinary levels of bone turnover markers were monitored. The serum level
      of undercarboxylated osteocalcin (uc-OC) was significantly lower (P < 0.001) in
      the menatetrenone group than in the control group (at 1 month), while there was a
      higher level of osteocalcin containing gamma-carboxylated glutamic acid (Gla-OC)
      in the menatetrenone group than the control group (P = 0.018). Significant
      differences of uc-OC and Gla-OC between the two groups were observed from 1 month
      onward. In addition, a higher level of intact osteocalcin was found in the
      menatetrenone group compared with the control group after 6 months (P = 0.006).
      Assessment of bone resorption markers showed that menatetrenone therapy was
      associated with significantly higher urinary N-telopeptide of type I collagen
      (NTX) excretion compared with the control group after 6 months, while there was
      no significant difference of urinary deoxypyridinoline excretion between the two
      groups. In conclusion, one month of menatetrenone therapy enhanced the secretion
      and gamma-carboxylation of osteocalcin, while urinary NTX excretion was increased
      after 6 months of treatment. Further investigations are required to determine
      whether the effects of menatetrenone on bone turnover are associated with
      fracture prevention.

PMID- 19172220
TI  - Potential utility of high preoperative levels of serum type I collagen markers in
      postmenopausal women with primary hyperparathyroidism with respect to their short
      term variations after parathyroidectomy.
AB  - We evaluated short-term changes in serum amino-terminal procollagen propeptide
      (P1NP) and cross-linked C-terminal telopeptide (betaCTX) of type I collagen after
      parathyroidectomy (PTX) in 41 postmenopausal women with primary
      hyperparathyroidism (PHPT). Serum levels of 25-hydroxyvitamin D, intact PTH,
      calcium, phosphate, albumin, creatinine, P1NP, and betaCTX were measured before
      and 2 days after PTX. Their P1NP and betaCTX levels were compared with those
      measured in 41 normally menstruating and 30 postmenopausal controls. Fifteen of
      these 41 women had both pre-surgery P1NP and betaCTX concentrations above the
      upper limit noted in our postmenopausal controls [high turnover (HT) subgroup],
      while betaCTX levels were solely above the upper limit lastly mentioned in 11
      women [high bone resorption (HBR) subgroup]. In addition, these two markers were
      within the postmenopausal control range in 12 of them [normal turnover (NT)
      subgroup]. A more significant decrease in postoperative betaCTX levels was
      observed in the 15 HT compared with the 12 NT PHPT women. The significant
      postoperative increase in P1NP levels observed in the 15 HT as well as in the 11
      HBR was no longer significant in the 12 NT women. In conclusion, higher pre
      surgery P1NP and betaCTX levels in post-menopausal PHPT women are associated with
      a preferential activation of bone formation over bone resorption after PTX.

PMID- 19172221
TI  - Nucleotide variations in genes encoding carbonic anhydrase 8 and 10 associated
      with femoral bone mineral density in Japanese female with osteoporosis.
AB  - Osteoporosis is a multi-factorial common disease, which is caused by combination
      of genetic as well as environmental factors. Among several factors, osteoclast
      acidification pathways during bone resorption might play an important role.
      Carbonic anhydrases, consisting of a gene family, are essential for pH regulation
      by the osteoclast. Clinically, use of carbonic anhydrase inhibitors has been
      known to be associated with a bone-sparing effect as judged by spine bone mineral
      density (BMD). Here, we investigated single nucleotide polymorphisms (SNPs) in
      carbonic anhydrase genes that are expressed in bone tissues, i.e., CA8 and CA10,
      for possible association with femoral and lumbar BMD among 337 Japanese women
      with osteoporosis participated in BioBank Japan project. Significant correlation
      was observed between CA8 SNP, rs6984526, and femoral BMD (P = 0.00029);
      homozygous carriers of the major (C) allele (n = 166) had the highest BMD (0.754
      +/- 0.006 g/cm(2), mean +/- SD), while heterozygous carriers (n = 135) were
      intermediate (0.741 +/- 0.07 g/cm(2)) and homozygous T-allele carriers (n = 31)
      had the lowest BMD (0.691 +/- 0.012 g/cm(2)). CA8 SNP as well displayed
      significant association with lumbar BMD in recessive model (P = 0.00017). In
      addition, CA10 SNP, rs2106329, also displayed strong association with femoral BMD
      (P = 0.00002). The results suggest that the variations of CA8 and CA10 loci may
      be important determinants of osteoporosis in Japanese women.

PMID- 19172222
TI  - Determinants of prevalent vertebral fractures and progressive bone loss in long
      term hemodialysis patients.
AB  - Skeletal fractures are common in hemodialysis (HD) patients. However, consensus
      regarding technique and site of bone examination has not been reached in HD
      patients. Seventy-two patients (44% females) aged 65 (1.4) years, treated with HD
      for 43 (4.6) months were examined with quantitative computed tomography and 53 of
      them re-examined after 1 year. Bone mineral density (BMD) of lumbar spine was
      established separately for cortical and trabecular bone, prevalent vertebral
      fractures were determined. Data are given as mean (standard error). At least one
      vertebral fracture was discovered in 15 (21%) patients. In a logistic regression
      model, fractures were best predicted by cortical BMD: OR 0.96 (CI 0.94, 0.99), p
      < 0.005. With a multiple regression analysis, time on dialysis was found to be
      independently correlated to cortical BMD (R = 0.35, p < 0.005). On follow-up, a
      decrease of BMD was detected, which occurred only in the cortical region and was
      significantly greater in females than in males: -7% (1.7) versus 1.2% (1.9), p <
      0.005. A time-dependent loss of vertebral cortical bone occurs in HD patients,
      especially in females. This decrement may impose an increased risk of fractures
      on long-term dialysis patients.

PMID- 19172223
TI  - The role of estrogen receptor-alpha gene TA polymorphism and aromatase gene TTTA
      polymorphism on peak bone mass attainment in males: is there an additive negative
      effect of certain allele combinations?
AB  - Idiopathic osteoporosis in males is influenced predominantly by low peak bone
      mass as a feature under a strong genetic control. Among a number of candidate
      genes, alpha-estrogen receptor (ERalpha) and CYP19 genes are of particular
      interest due to important role of estrogen in pathophysiology of osteoporosis. In
      the present study we examined the association of certain allelic combinations of
      ERalpha gene thymine-adenine (TA) polymorphism and aromatase gene TTTA
      polymorphism on bone mineral density (BMD) in young men. The study sample
      consisted of 92 unrelated healthy male volunteers, aged 21-35. In each subject,
      lumbar spine and proximal femur BMD, parameters of bone turnover and 25-OHD level
      were measured. Two ERalpha (TA)( n ) alleles, allele 19 and allele 21, were found
      to be associated with lower BMD. The presence of allele 19 was associated with
      significantly lower lumbar spine (P = 0.006) and trochanter (P = 0.02) BMD while
      the subjects positive for allele 21 had significantly lower lumbar spine (P =
      0.04), trochanter (P = 0.02) and total hip (P = 0.03) BMD. Men with CYP19
      (TTTA)(7-3)/ERalpha (TA)(19) allele combination had significantly lower lumbar
      spine BMD (P = 0.02) and those with CYP19 (TTTA)(7-3)/ERalpha (TA)(21) allele
      combination had significantly lower BMD for all three measurements, i.e. lumbar
      spine (P = 0.02), femoral neck (P = 0.02) and total hip (P = 0.008). These
      particular combinations of high-risk alleles were associated with lower median
      lumbar spine, femoral neck and total hip BMD than either of the allele alone
      suggesting that negative effect of two risk alleles on peak bone mass add up.

PMID- 19172224
TI  - Bone mineral density measurement in puerperal women as a predictor of persistent
      osteopenia.
AB  - The clinical value of bone mineral density (BMD) measurement in puerperal women
      is uncertain. Our aim was to examine the effectiveness of BMD measurement in
      puerperal women for identification of persistent osteopenia and osteoporosis. We
      addressed cross-sectional and longitudinal changes in BMD, assessed using dual
      energy X-ray absorptiometry (DXA), in a postpartum female cohort from a single
      center in Japan. We measured BMD of the lumbar spine (L2-L4) with DXA in 2,436
      puerperal women within 7 days of delivery (study 1). For 210 of the women, the
      BMD was measured again after 5-10 years (study 2). In study 1, 8 (0.3%) of the
      women were osteoporotic, 37 (17.0%) were osteopenic, and 2,013 (82.6%) were
      normal. In study 2, 27 (71.1%) of the 38 osteoporotic or osteopenic women
      identified in the puerperal scan were still osteopenic at the scan after 5-10
      years. Over the same period, only 7 (4.1%) of 172 initially normal women became
      osteopenic. The mean of the BMD change per year was 0.15 +/- 0.82%/year.
      Osteopenia was associated with a significantly lower body weight and body mass
      index at puerperium and after 5-10 years compared to normal women. The multiple
      regression analysis showed that BMD at the first scan negatively contributed and
      body weight changes between the scans positively significantly contributed to the
      BMD changes per year. Puerperal BMD remained static over the subsequent 5-10
      years. If the women have a low BMD at this stage of their reproductive life, it
      tends not to improve over this time. Perhaps identification of this at-risk group
      may lead to effective interventions to reduce fracture risk in later life.

PMID- 19172225
TI  - Inhibition of the classical NF-kappaB pathway prevents osteoclast bone-resorbing
      activity.
AB  - The classical NF-kappaB pathway plays an important role in osteoclast formation
      and differentiation; however, the role of NF-kappaB in osteoclast bone-resorbing
      activity is not well understood. To elucidate whether NF-kappaB is important for
      osteoclast bone-resorbing activity, we used a selective peptide inhibitor of the
      classical NF-kappaB pathway named the NBD peptide. Osteoclasts were generated
      using bone marrow macrophages in the presence of M-CSF and RANKL. The NBD peptide
      dose-dependently blocked the bone-resorbing activity of osteoclasts by reducing
      area, volume (p < 0.001) and depths (p < 0.05) of pits. The reduced resorption by
      the peptide was due to reduced osteoclast bone-resorbing activity, but not
      reduced differentiation as the number of osteoclasts was similar in all groups.
      The peptide inhibited bone resorption by reducing TRAP activity, disrupting actin
      rings and preventing osteoclast migration. Gene expressions of a panel of bone
      resorption markers were significantly reduced. The NBD peptide dose-dependently
      reduced the RANKL-induced c-Src kinase activity, which is important for actin
      ring formation and osteoclast bone resorption. Therefore, these data suggest that
      the classical NF-kappaB pathway plays a pivotal role in osteoclast bone-resorbing
      activity.

PMID- 19172226
TI  - Good maintenance of physical benefits in a 12-month exercise and nutritional
      intervention by voluntary, home-based exercise: a 6-month follow-up of a
      randomized controlled trial.
AB  - We assessed the maintenance of physical benefits in a 12-month exercise and
      nutritional intervention in postmenopausal women (55-75 years of age) after 6
      month postintervention follow-up by voluntary, home-based exercise, and examined
      whether physical factors responded differently to high or low exercise frequency
      during the 6-month postintervention period. Forty-five women completed the 12
      month intervention program, followed by 6-month cessation of intervention, and
      were compared with 19 matched controls. Twenty-one of the former exercisers
      reported that they continued exercise training at least 30 min at least 3
      days/week (high-frequency exerciser, HFE), while the remaining 24 former
      exercisers reported that they had done exercise training at least 30 min twice
      per week or less during the postintervention follow-up (low-frequency exerciser,
      LFE). The following items were measured at baseline, 12, and 18 months: bone
      strength, CS-30 test, 10-m obstacle walk, whole-body reaction time, one-leg
      stance, and grip strength. After 6-month postintervention follow-up, the
      beneficial effect on bone was not fully maintained. These benefits in physical
      performance obtained in the 12-month intervention program, except one-leg stance,
      were fully maintained for 6 months by voluntary, home-based exercise. The gained
      benefit in one-leg stance was not fully maintained; LFE showed a significant
      decrease over the 6-month postintervention follow-up period, suggesting that
      continued exercise training of at least 30 min at least 3 days/week is required
      to maintain the balance benefit. These findings suggest that a continued exercise
      program of voluntary, home-based exercise may be effective to maintain the
      physical benefits of exercise intervention that may lower fracture risk in later
      life.

PMID- 19172227
TI  - Treatment of juxta-articular intraosseous cystic lesions in rheumatoid arthritis
      patients with interconnected porous calcium hydroxyapatite ceramic.
AB  - In patients with rheumatoid arthritis (RA), juxta-articular intraosseous cystic
      lesions may cause spontaneous pathological fractures. The outcome of curettage
      and the packing of such lesions with interconnected porous calcium hydroxyapatite
      ceramic (IP-CHA) was investigated. Twelve lesions were treated in ten RA patients
      (three men and seven women with a mean age of 59 years). Ten lesions were
      associated with impending pathological fracture involving the articular surface.
      In all patients, curettage and packing of the bone cavity with IP-CHA were done.
      Assessment was based on final radiographs obtained an average of 30 months after
      surgery (range 10-47 months). Absorption of the implanted IP-CHA, expansion of
      the lesion, implant incorporation into host bone, and postoperative fractures
      were investigated. At final follow-up, there was no absorption of the implanted
      IP-CHA in any of the lesions. Expansion of the radiolucent area was only noted in
      one lesion. Seven of the other 11 lesions showed major incorporation of IP-CHA
      into host bone, while minor incorporation was seen in four lesions. There were no
      postoperative fractures. In conclusion, curettage and packing with IP-CHA is a
      feasible method of preventing pathological fracture due to juxta-articular
      intraosseous cystic lesions in RA patients.

PMID- 19172228
TI  - Melatonin treatment decreases c-fos expression in a headache model induced by
      capsaicin.
AB  - The aim of the present work was to analyze c-fos response within the trigeminal
      nucleus caudalis (TNC) of pinealectomized rats and animals that received
      intraperitoneal melatonin, after intracisternal infusion of capsaicin, used to
      induce intracranial trigeminovascular stimulation. Experimental groups consisted
      of animals that received vehicle solution (saline-ethanol-Tween 80, 8:1:1,
      diluted 1:50) only (VEI, n=5); animals that received capsaicin solution (200 nM)
      only (CAP, n=6); animals submitted to pinealectomy (PX, n=5); sham-operated
      animals (SH, n=5); animals submitted to pinealectomy followed by capsaicin
      stimulation (200 nM) after 15 days (PX + CAP, n=7); and animals that received
      capsaicin solution (200 nM) and intraperitoneal melatonin (10 mg/kg) (CAP + MEL,
      n=5). Control rats, receiving vehicle in the cisterna magna, showed a small
      number of c-fos-positive cells in the TNC (layer I/II) as well as the sham
      operated and pinealectomized rats, when compared to animals stimulated by
      capsaicin. On the other hand, pinealectomized rats, which received capsaicin,
      presented the highest number of c-fos-positive cells. Animals receiving capsaicin
      and melatonin treatment had similar expression of the vehicle group. Our data
      provide experimental evidence to support the role of melatonin and pineal gland
      in the pathophysiology of neurovascular headaches.

PMID- 19172229
TI  - The preclinical activity of the histone deacetylase inhibitor PXD101 (belinostat)
      in hepatocellular carcinoma cell lines.
AB  - The activity of the histone deacetylase inhibitor PXD101 was investigated in
      three hepatocellular carcinoma (HCC) cell lines. PXD101 was found to inhibit cell
      growth at a dose-dependent manner and induce histone acetylation in PLC/PRF/5,
      Hep3B and HepG2 cells. In PLC/PRF/5 and Hep3B cells which express hepatitis B
      related genes (HBx, HBc and HBc), treatment with PXD101 resulted in apoptosis
      without a significant effect on viral gene expression. Exposure to PXD101 for up
      to 48 h had varying effects on the expression of 12 cellular genes with tumor
      suppressor functions, including p21, SOCS1, CMTM5, RASAL1, DLEC1, SFRP (-1, -2, 
      4 and -5), ADAMTS (-8 and -9). This study provided the basis for a phase II
      clinical trial of PXD101 in inoperable hepatitis-B associated HCC.

PMID- 19172230
TI  - Insertion of a heterologous gene construct into a non-functional ORF of the
      Streptococcus thermophilus chromosome.
AB  - An integrative vector was constructed for inserting heterologous genes within a
      non-functional open reading frame (ORF) on the chromosome of Streptococcus
      thermophilus. The vector, pINTRS, contained a temperature sensitive origin of
      replication and an erythromycin resistance gene for initial selection in S.
      thermophilus. The region of the vector containing unique cloning sites, for
      insertion of recombinant genes, was flanked by homologous DNA sequences
      corresponding to a pseudogene in S. thermophilus to facilitate chromosomal
      integration. The gene encoding green fluorescent protein, regulated by a plasmid
      borne hsp promoter of S. thermophilus, was cloned into pINTRS to demonstrate
      proper functioning of the vector.

PMID- 19172231
TI  - Effect of cadmium on cellular viability in two species of microalgae (Scenedesmus
      sp. and Dunaliella viridis).
AB  - We determined the effect of several concentrations of cadmium (0, 5, 10, and 20
      microg/l) on cellular viability in the microalgae Scenedesmus sp. and Dunaliella
      viridis, by measuring growth at 0, 24, 48, 72, and 96 h and pigment production at
      10 days. Algae were obtained from the Nonvascular Plant Laboratory collection, in
      the Facultad Experimental de Ciencias, Universidad del Zulia, Venezuela. Growth
      was measured by cellular counting, while pigment content was evaluated using
      conventional spectrophotometric techniques. Growth of both species decreased in
      the exposed cultures comparing with the control, but its behavior was similar,
      because in both control and exposed cultures, its was observed an adaptive phase
      in the first hours, as well as a growth phase after 72 h. Cadmium concentrations
      above 10 microg/l produced an adverse effect on pigment production, depending on
      the concentration and/or exhibition time. However, even though cadmium inhibited
      growth and pigment production, levels of both parameters indicated cellular
      viability, demonstrating the adaptability of the algae cultures when they were
      exposed to the metal.

PMID- 19172232
TI  - Cytotoxicity of bacterial-derived toxins to immortal lung epithelial and
      macrophage cells.
AB  - Health risks associated with inhalation and deposition of biological materials
      have been a topic of great concern due to highly publicized cases of inhalation
      anthrax, of new regulations on the release of particulate matter, and to
      increased concerns on the hazards of indoor air pollution. Here, we present an
      evaluation of the sensitivity of two immortal cell lines (A549, human lung
      carcinoma epithelia) and NR8383 (rat alveolar macrophages) to a variety of
      bacterial-derived inhalation hazards and simulants including etoposide,
      gliotoxin, streptolysin O, and warfarin. The cell response is evaluated through
      quantification of changes in mitochondrial succinate dehydrogenase activity,
      release of lactate dehydrogenase, initiation of apoptosis, and through changes in
      morphology as determined by visible light microscopy and scanning electron
      microscopy. These cells display dose-response relations to each toxin, except for
      triton which has a step change response. The first observable responses of the
      epithelial cells to these compounds are changes in metabolism for one toxin
      (warfarin) and alterations in membrane permeability for another (gliotoxin). The
      other four toxins display a similar time course in response as gauged by changes
      in metabolism and loss of membrane integrity. Macrophages are more sensitive to
      most toxins; however, they display a lower level of stability. This information
      can be used in the design of cell-based sensors responding to these and similar
      hazards.

PMID- 19172233
TI  - Expression of transcriptional repressor Slug gene in mouse endometrium and its
      effect during embryo implantation.
AB  - Slug, a member of the Snail family of zinc-finger transcription factors, is
      involved in regulating embryonic development and tumorigenesis. The aim of this
      study was to investigate the expression of Slug in mouse endometrium during early
      pregnancy and its possible role during embryo implantation. Fluorescence
      quantitative polymerase chain reaction and immunohistochemistry were applied to
      detect Slug mRNA and Slug protein expression in endometrium of nonpregnant and
      early pregnant mice, respectively. The expressions of Slug mRNA and its protein
      in pregnant group were higher than that in nonpregnant group and gradually
      increased from pregnancy day 1, reaching its maximum level on day 4 and then
      declining on days 5, 6, and 7. Immunohistochemistry showed that Slug protein was
      mainly present in luminal epithelium from pregnancy days 2 to 5 and in glandular
      epithelium from days 2 to 6 and enhanced significantly in stromal cells on days
      4, 5, and 6. The number of embryos implanted was greatly decreased after Slug
      function in mouse endometrium was blocked by the intrauterine injection with anti
      Slug polyclonal antibody on day 3 of pregnancy before implantation. These results
      suggested that up-regulation of Slug expression may play a key role in the embryo
      implantation in mice.

PMID- 19172234
TI  - An improved end-point fluorimetric procedure for the determination of low amounts
      of trypsin activity in biological samples using rhodamine-110-based substrates.
AB  - A novel end-point fluorimetric procedure based on the use of rhodamine-110
      labeled specific substrate was developed to determine trypsin activities in
      biological samples. We evaluated the ability of trichloroacetic acid and acetic
      acid to stop the enzymatic reaction without hindering the detection of the
      fluorescence of rhodamine-110 released into the reaction mixture from the
      specific substrate (CBZ-L-alanyl-L-arginine)(2)-rhodamine-110. Trichloroacetic
      acid decreased markedly the fluorescence of rhodamine-110, even at low
      concentrations. On the other hand, the addition of 50 mmol/l acetic acid
      inactivated efficiently trypsin activity, causing minor effects on rhodamine-110
      fluorescence. The proposed procedure was more sensitive than the
      spectrophotometric end-point method using N-alpha-benzoyl-DL-arginine-p
      nitroanilide as substrate. The possibility of carrying out end-point fluorimetric
      assays improves the performance of monocell fluorimeters by setting specific
      conditions optimal for each enzyme activity independently of the fluorimeter.
      This method also allows replicate assays to be conducted simultaneously,
      resulting in considerable time saving and in increased performance of low-cost
      equipment.

PMID- 19172235
TI  - Microbial fuel cells: the effects of configurations, electrolyte solutions, and
      electrode materials on power generation.
AB  - This objective of this study is to conduct a systematic investigation of the
      effects of configurations, electrolyte solutions, and electrode materials on the
      performance of microbial fuel cells (MFC). A comparison of voltage generation,
      power density, and acclimation period of electrogenic bacteria was performed for
      a variety of MFCs. In terms of MFC configuration, membrane-less two-chamber MFCs
      (ML-2CMFC) had lower internal resistance, shorter acclimation period, and higher
      voltage generation than the conventional two-chamber MFCs (2CMFC). In terms of
      anode solutions (as electron donors), the two-chamber MFCs fed with anaerobic
      treated wastewater (AF-2CMFCs) had the power density 19 times as the two-chamber
      MFCs fed with acetate (NO(3)(-)2CMFCs). In terms of cathode solutions (as
      electron acceptors), AF-2CMFCs with ferricyanide had higher voltage generation
      than that of ML-2CMFCs with nitrate (NO(3)(-)ML-2CMFCs). In terms of electrode
      materials, ML-2CMFCs with granular-activated carbon as the electrode (GAC-ML
      2CMFCs) had a power density 2.5 times as ML-2CMFCs with carbon cloth as the
      electrode. GAC-ML-2CMFCs had the highest columbic efficiency and power output
      among all the MFCs tested, indicating that the high surface area of GAC
      facilitate the biofilm formation, accelerate the degradation of organic
      substrates, and improve power generation.

PMID- 19172236
TI  - Engineering Escherichia coli for fermentative dihydrogen production: potential
      role of NADH-ferredoxin oxidoreductase from the hydrogenosome of anaerobic
      protozoa.
AB  - Trichomonas vaginalis generates reduced ferredoxin within a unique subcellular
      organelle, hydrogenosome that is used as a reductant for H2 production. Pyruvate
      ferredoxin oxidoreductase and NADH dehydrogenase (NADH-DH) are the two enzymes
      catalyzing the production of reduced ferredoxin. The genes encoding the two
      subunits of NADH-DH were cloned and expressed in Escherichia coli. Kinetic
      properties of the recombinant heterodimer were similar to that of the native
      enzyme from the hydrogenosome. The recombinant holoenzyme contained 2.15 non-heme
      iron and 1.95 acid-labile sulfur atoms per heterodimer. The EPR spectrum of the
      dithionite-reduced protein revealed a [2Fe-2S] cluster with a rhombic symmetry of
      gxyz = 1.917, 1.951, and 2.009 corresponding to cluster N1a of the respiratory
      complex I. Based on the Fe content, absorption spectrum, and the EPR spectrum of
      the purified small subunit, the [2Fe-2S] cluster was located in the small subunit
      of the holoenzyme. This recombinant NADH-DH oxidized NADH and reduced low redox
      potential electron carriers, such as viologen dyes as well as Clostridium
      ferredoxin that can couple to hydrogenase for H2 production from NADH. These
      results show that this unique hydrogenosome NADH dehydrogenase with a critical
      role in H2 evolution in the hydrogenosome can be produced with near-native
      properties in E. coli for metabolic engineering of the bacterium towards
      developing a dark fermentation process for conversion of biomass-derived sugars
      to H2 as an energy source.

PMID- 19172237
TI  - Production of milk-clotting protease from Bacillus subtilis.
AB  - An indigenous Bacillus subtilis strain isolated from soil was found to be a
      potent milk-clotting protease (mcp) producer. Production optimized using response
      surface methodology (RSM) yielded 1,190 U/ml of enzyme in medium containing 6%
      fructose, 1% casein, 0.3% NH4NO3, 10 mM CaCl2, pH 6.0 and inoculated with 3%
      inoculum and incubated at 250 rpm for 72 h. Solid-state fermentation resulted in
      1,080 and 952.3 U/gds of milk-clotting protease using soybean meal and rice bran,
      respectively, with higher proteolytic values of 18.97 and 9.1 IU/gds. Production
      in a biphasic system using an overlay of RSM-optimized medium on solid layer of
      6% fructose and 1% casein with 1.5% agar resulted in significant enzyme
      production. Maximum mcp was obtained using a biphasic system where solid: liquid
      ratio of 3.0 resulted in a final yield of 1,276.65 U/ml with a yield index of
      1.80 as compared to static liquid culture. However, significant increase or
      difference was noted as compared to yield obtained after RSM. This is the first
      report on the use of RSM for production of mcp from a bacterial species.

PMID- 19172238
TI  - Modeling biomass gasification using thermodynamic equilibrium approach.
AB  - In this paper, the thermodynamic equilibrium models for biomass gasification
      applicable to various gasifier types have been developed, with and without
      considering char. The equilibrium models were then modified closely matching the
      CH(4) only or both CH(4) and CO compositions from experimental data. It is shown
      that the modified model presented here based on thermodynamic equilibrium and
      taking into account local heat and mass considerations can be used to simulate
      the performance of a downdraft gasifier. The model can also be used to estimate
      the equilibrium composition of the syngas. Depending on the gasifier type and
      internal fluid flow, heat and mass transfer characteristics, with proper
      modification of the equilibrium model, a simple tool to simulate the operation
      and performance of varying types of biomass gasifier can be developed.

PMID- 19172239
TI  - Temsirolimus in patients with advanced renal cell carcinoma: an overview.
AB  - Treatment of patients with advanced renal cell carcinoma (RCC) has changed
      dramatically with the advent of targeted therapeutics. Temsirolimus, an inhibitor
      of mammalian target of rapamycin (mTOR), has proven beneficial in the treatment
      of advanced RCC with poor prognosis. The rationale for mTOR inhibitors in
      treatment of RCC, the pharmacokinetics and toxicities of temsirolimus, landmark
      clinical trials of temsirolimus in advanced RCC, and the indications for its use
      in the treatment of RCC are reviewed here. The status of temsirolimus in the
      rapidly evolving therapeutic landscape of advanced RCC is also discussed.

PMID- 19172240
TI  - [Modern morphological diagnosis and current classification of soft tissue
      sarcomas].
AB  - Malignant soft tissue tumors are somewhat rare, and thus sufficient experience in
      diagnostics and therapy of these sarcomas is available as a rule only at
      specialist centers. The gold standard of morphological diagnosis is still
      represented by evaluation of HE-stained histological sections. However modern
      methods of examination are also helpful in diagnosis. Because
      immunohistochemistry is now used routinely, emphasis in this article is laid on
      molecular methods with special reference to fluorescence in-situ hybridization
      (FISH) and reverse transcriptase polymerase chain reaction. Principles of the WHO
      soft tissue tumor classification are explained, and the changed or expanded
      interpretation of some tumor entities is illustrated using the example of
      atypical lipomatous tumors, so-called malignant fibrous histiocytomas and
      hemangiopericytomas, fibrosarcomas, and inflammatory myofibroblastic tumors.

PMID- 19172241
TI  - Ethyl pyruvate improves survival in awake hemorrhage.
AB  - Classical experimental models of hemorrhage are characterized by the use of
      anesthetics that may interfere with the typical immune responses and pathology of
      hemorrhage/resuscitation. Thus, therapeutic strategies successful in anesthetized
      animals might not be beneficial in clinical trials. In this study, we analyzed
      whether ethyl pyruvate could provide therapeutic benefits during resuscitation in
      awake (unanesthetized) hemorrhage. Our results indicate that hemorrhage in
      unanesthetized animals required approximately 25% higher blood withdrawal than
      anesthetized animals to achieve the same targeted mean arterial blood pressure.
      Resuscitation with Hextend reestablished circulatory volume and improved survival
      during resuscitation of awake rodents. Yet, over 75% of the animals resuscitated
      with Hextend died within the first hours after hemorrhage. Resuscitation with
      Hextend containing 50 mM ethyl pyruvate protected over 87% of the animals. This
      survival benefit did not correlate with significant changes in the metabolic
      markers but with an anti-inflammatory potential during resuscitation. Unlike
      classical hemorrhage in anesthetized animals, ethyl pyruvate reestablished mean
      arterial blood pressure significantly earlier than Hextend in unanesthetized
      rodents. Unanesthetized animals showed twofold higher serum tumor necrosis factor
      (TNF)-alpha than anesthetized animals subjected to the same blood pressure. This
      process was not due to the response of a single organ, but affected all the
      analyzed organs including the lung, heart, spleen, and liver. Although
      resuscitation with Hextend failed to attenuate systemic TNF-alpha levels, it
      inhibited TNF-alpha levels in the lung, heart, and liver but not in the spleen.
      Unlike Hextend, resuscitation with ethyl pyruvate prevented high serum TNF-alpha
      levels and blunted TNF-alpha responses in all the organs including the spleen.
      These studies indicate that the inflammatory responses in anesthetized animals
      differ from that in unanesthetized animals and that awake hemorrhage can provide
      advantages in the study of anti-inflammatory strategies during resuscitation.
      Ethyl pyruvate may attenuate systemic inflammatory responses during resuscitation
      and improve survival in experimental models of awake hemorrhage.

PMID- 19172242
TI  - [Operative treatment of traumatic fractures of the thorax and lumbar spine. Part
      II: surgical treatment and radiological findings].
AB  - The Spine Study Group (AG WS) of the German Trauma Association (DGU) presents its
      second prospective Internet-based multicenter study (MCS II) for the treatment of
      thoracic and lumbar spinal injuries. This second part of the study report focuses
      on the surgical treatment, course of treatment, and radiological findings in a
      study population of 865 patients. A total of 158 (18,3%) thoracic, 595 (68,8%)
      thoracolumbar, and 112 (12,9%) lumbar spine injuries were treated. Of these, 733
      patients received operative treatment (OP group). Fifty-two patients were treated
      non-operatively and 69 patients were treated with kyphoplasty/vertebroplasty
      without additional instrumentation (Plasty group). In the OP group, 380 (51.8%)
      patients were instrumented from a posterior (dorsal) position, 34 (4.6%) from an
      anterior (ventral) position, and 319 (43.5%) cases with a combined
      posteroanterior procedure. Angular stable internal spine fixator systems were
      used in 86-97% of the cases for posterior and/or combined posteroanterior
      procedures. For anterior procedures, angular stable plate systems were used in a
      majority of cases (51.1%) for the instrumentation of mainly one or two segment
      lesions (72.7%). In 188 cases (53,3%), vertebral body replacement implants
      (cages) were used and were mainly implanted via endoscopic approaches (67,4%) to
      the thoracic spine and/or the thoracolumbar junction. The average operating time
      was 152 min in posterior-, 208 min in anterior-, and 298 min in combined postero
      anterior procedures (p<0,001). The average blood loss was highest in combined
      operations, measuring 959 ml vs. 650 ml in posterior vs. 534 ml in anterior
      operations (p<0,001).Computer-assisted intraoperative navigation systems were
      used in 95 cases. At the time of hospital admission, 58,7% of the patients had
      spinal canal narrowing of an average of 36% (5-95%) at the level of their injury.
      The average spinal canal narrowing in patients with a complete spinal cord injury
      (Frankel/ASIA A) was calculated to be 70%, vs. 50% in patients with incomplete
      neurologic deficits (Frankel/ASIA B-D), and 20% in patients without neurologic
      deficits (Frankel/ASIS E; p<0,001). The average procedure in the plasty treatment
      subgroup was 50 min (18-145 min) to address one (n=59) or two (n=10) injured
      vertebral bodies. In patients with nonoperative treatment mainly three-point
      corsets (n=36) were administered for a duration of 6-12 weeks. During their
      hospital stay 93 of 195 (44,7%) patients with initial neurologic deficits
      improved at least one Frankel/ASIA grade until the day of discharge. Two patients
      (0,2%) showed a neurologic deterioration. The highest rate of complete spinal
      cord injury (n=36, 23%) was associated with thoracic spine injuries. Nine (1%)
      patients died during the initial course of treatment. A total of 105 (14,3%)
      cases with intraoperative (n=56) and/or postoperative complications (n=69) were
      registered. The most common intraoperative complication was bleeding (n=35,
      4,8%). A higher relative frequency of intraoperative complications was noticed in
      combined (n=34, 10,7%) vs. isolated posterior (n=22, 5,9%; p=0,021) procedures.
      The most common postoperative complication was associated with wound healing
      problems in 14 (1,9%) patients. Except in the non-operative treatment subgroup, a
      correction of the posttraumatic measured radiological deformity was achieved to a
      different extent within every treatment subgroup. There were no statistically
      significant differences between the postoperative radiological results of the
      treatment subgroups (dorsal vs. combination), taking into consideration the
      influence of relevant parameters such as different fracture types, patient age,
      and the amount of posttraumatic deformity (p=0,34, ANOVA).

PMID- 19172243
TI  - A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type
      2 diabetic patients: a randomised placebo-controlled study.
AB  - AIMS/HYPOTHESIS: Cu(II)-selective chelation with trientine ameliorates
      cardiovascular and renal disease in a model of diabetes in rats. Here, we tested
      the hypothesis that Cu(II)-selective chelation might improve left ventricular
      hypertrophy (LVH) in type 2 diabetic patients. METHODS: We performed a 12 month
      randomised placebo-controlled study of the effects of treatment with the Cu(II)
      selective chelator trientine (triethylenetetramine dihydrochloride, 600 mg given
      orally twice daily) on LVH in diabetic patients (n = 15/group at baseline) in an
      outpatient setting wherein participants, caregivers and those assessing outcomes
      were blinded to group assignment. Using MRI, we measured left ventricular
      variables at baseline, and at months 6 and 12. The change from baseline in left
      ventricular mass indexed to body surface area (LVM(bsa)) was the primary endpoint
      variable. RESULTS: Diabetic patients had LVH with preserved ejection fraction at
      baseline. Trientine treatment decreased LVM(bsa) by 5.0 +/- 7.2 g/m(2) (mean +/-
      SD) at month 6 (when 14 trientine-treated and 14 placebo-treated participants
      were analysed; p = 0.0056 compared with placebo) and by 10.6 +/- 7.6 g/m(2) at
      month 12 (when nine trientine-treated and 13 placebo-treated participants were
      analysed; p = 0.0088), whereas LVM(bsa) was unchanged by placebo treatment. In a
      multiple-regression model that explained ~75% of variation (R (2) = 0.748, p =
      0.001), cumulative urinary Cu excretion over 12 months was positively associated
      with trientine-evoked decreases in LVM(bsa). CONCLUSIONS/INTERPRETATION: Cu(II)
      selective chelation merits further exploration as a potential pharmacotherapy for
      diabetic heart disease. TRIAL REGISTRATION: Australian New Zealand Clinical
      Trials Registry ACTRN 12609000053224 FUNDING: The Endocore Research Trust;
      Lottery Health New Zealand; the Maurice and Phyllis Paykel Trust; the Foundation
      of Research, Science and Technology (New Zealand); the Health Research Council of
      New Zealand; the Ministry of Education (New Zealand) through the Maurice Wilkins
      Centre for Molecular Biodiscovery; and the Protemix Corporation.

PMID- 19172244
TI  - The risk allele load accelerates the age-dependent decline in beta cell function.
AB  - AIMS/HYPOTHESIS: Among the novel type 2 diabetes risk loci identified by genome
      wide association studies, TCF7L2, HHEX, SLC30A8 and CDKAL1 appear to affect beta
      cell function. In the present study we examined the effect of these genes' risk
      alleles on the age-dependent decline in insulin secretion. METHODS: The SNPs
      rs7903146 (TCF7L2), rs7754840(CDKAL1), rs7923837 (HHEX) and rs13266634 (SLC30A8)
      were genotyped in 1,412 non-diabetic patients, who were subsequently grouped
      according to their number of risk alleles. All participants underwent an OGTT.
      Insulin secretion was assessed by validated indices and proinsulin conversion by
      calculating AUC(proinsulin)/AUC(insulin). RESULTS: The number of risk alleles
      revealed a Gaussian distribution, with most participants carrying four risk
      alleles. Stratification into groups with low (LAL, up to three alleles), median
      (MAL, four alleles) and high (HAL, five to eight alleles) allele load resulted in
      MAL and HAL participants displaying significantly lower insulin secretion and
      proinsulin conversion than LAL participants (p <or= 0.0014 and p = 0.0185,
      respectively). In the overall cohort, age was negatively associated with insulin
      secretion and proinsulin conversion (both p < 0.0001). MAL and HAL participants
      showed a significantly more pronounced decline in insulin secretion with
      increasing age than LAL participants (p <or= 0.0325; analysis of covariance), and
      after stratification for BMI this relationship was maintained in obese, but not
      non-obese, participants. Proinsulin conversion decreased with increasing age in
      MAL and HAL, but not LAL, participants (p <or= 0.0003 vs p = 0.2).
      CONCLUSIONS/INTERPRETATION: The risk allele load significantly accelerates the
      age-dependent decline in beta cell function, and this might be of particular
      importance in obese people.

PMID- 19172245
TI  - [Selective fusion of idiopathic scoliosis with respect to the Lenke
      classification].
AB  - Indications for surgical treatment of idiopathic scoliosis are progressive curves
      greater than 40-50 degrees. In most cases, fusion of only the primary
      (structural) curve(s) is sufficient due to the flexibility and spontaneous
      correction of the secondary curves. Therefore, it is crucial to identify both
      primary and secondary curves. According to the Lenke classification, all curves
      with a residual curve of more than 25 degrees on the bending films and those with
      a pathological kyphosis are regarded as structural and should be fused, whereas
      the nonstructural curves can be left unfused. However, according to reports in
      the literature and to the author's experience, clinical parameters such as
      shoulder level and rib or lumbar hump as well as radiometric criteria such as
      rotation are relevant as well. In summary, the Lenke classification is an
      important and helpful tool for analysing idiopathic curves and determining fusion
      length, even though each scoliosis case needs to be evaluated individually,
      especially taking clinical parameters into account.

PMID- 19172246
TI  - Carbon dioxide monitoring during long-term noninvasive respiratory support in
      children.
AB  - INTRODUCTION: Routine monitoring of noninvasive respiratory support relies on
      nocturnal pulse oximetry and daytime arterial blood gases, without systematic
      nocturnal carbon dioxide recording. The aim of the study was to assess if
      overnight pulse oximetry and daytime blood gases are sufficiently accurate to
      detect nocturnal hypoventilation in children receiving long-term noninvasive
      respiratory support. MATERIALS AND METHODS: Pulse oximetry and carbon dioxide
      pressure measured by capillary arterialized blood gases and a combined
      transcutaneous carbon dioxide and pulse oximetry (PtcCO(2)/SpO(2)) monitor were
      compared in 65 patients (asthma, n = 16, recurrent bronchitis, n = 8, lung
      infection, n = 8, cystic fibrosis, n = 15, interstitial lung disease, n = 6,
      neuromuscular disease, n = 12). Daytime capillary arterialized blood gases and
      nocturnal recording of pulse oximetry and carbon dioxide by means of a combined
      PtcCO(2)/SpO(2) monitor were performed in 50 other patients receiving nocturnal
      noninvasive respiratory support at home. RESULTS: A correlation was observed
      between pulse oximetry (r = 0.832, P < 0.0001) and carbon dioxide pressure (r =
      0.644, P < 0.0001) measured by capillary arterialized blood gases and the
      combined PtcCO(2)/SpO(2) monitor. Twenty-one of the 50 patients (42%) on long
      term noninvasive respiratory support presented nocturnal hypercapnia, defined by
      a PtcCO(2) value >50 mmHg, without nocturnal hypoxemia. Daytime capillary
      arterialized carbon dioxide levels were normal in 18 of these 21 patients.
      CONCLUSIONS: Nocturnal hypercapnia may occur in children receiving nocturnal
      noninvasive respiratory support at home. Nocturnal pulse oximetry and daytime
      arterial blood gases are not sufficiently accurate to diagnose nocturnal
      hypercapnia, underlying the importance of a systematic carbon dioxide monitoring
      in children receiving noninvasive respiratory support.

PMID- 19172247
TI  - Caspofungin for prevention of intra-abdominal candidiasis in high-risk surgical
      patients.
AB  - PURPOSE: Thirty to forty percent of patients with recurrent gastrointestinal
      perforation/anastomotic leakage or acute necrotizing pancreatitis develop intra
      abdominal invasive candidiasis (IC). A corrected Candida colonization index (CCI)
      > or =0.4 is a powerful predictor of IC. Fluconazole prevents intra-abdominal IC
      in this setting, but azole-resistant Candida species are emerging. The aim of
      this study was to explore the efficacy and safety of caspofungin for prevention
      of intra-abdominal IC in high-risk surgical patients. METHODS: Prospective non
      comparative single-center study in consecutive adult surgical patients with
      recurrent gastrointestinal perforation/anastomotic leakage or acute necrotizing
      pancreatitis. Preventive caspofungin therapy (70 mg, then 50 mg/day) was given
      until resolution of the surgical condition. Candida colonization index and CCI,
      occurrence of intra-abdominal IC and adverse events were monitored. RESULTS:
      Nineteen patients were studied: 16 (84%) had recurrent gastrointestinal
      perforation/anastomotic leakage and 3 (16%) acute necrotizing pancreatitis. The
      median duration of preventive caspofungin therapy was 16 days (range 4-46). The
      colonization index decreased significantly during study therapy, and the CCI
      remained <0.4 in all patients. Caspofungin was successful for prevention of intra
      abdominal IC in 18/19 patients (95%, 1 breakthrough IC 5 days after inclusion).
      No drug-related adverse event requiring caspofungin discontinuation occurred.
      CONCLUSION: Caspofungin may be efficacious and safe for prevention of intra
      abdominal candidiasis in high-risk surgical patients. This needs to be further
      investigated in randomized trials.

PMID- 19172248
TI  - How reliable are G-protein-coupled receptor antibodies?
AB  - A cluster of manuscripts in this issue of the Journal highlights a lack of
      selectivity of 49 antibodies against 19 subtypes of alpha(1)- and beta
      adrenoceptors, muscarinic, dopamine and galanin receptors as well as vanilloid
      (TRPV1) receptors. Taken together these data demonstrate that lack of selectivity
      appears to be the rule rather than the exception for antibodies against G-protein
      coupled and perhaps also other receptors. Thus, the previously often applied
      validation of such antibodies by the disappearance of staining in the presence of
      blocking peptide, i.e. the antigen against which the antibody was raised, alone
      is insufficient to demonstrate specificity. We propose that receptor antibodies
      should be validated by at least one of the following techniques: a) disappearance
      of staining in knock-out animals of the target receptor, b) reduction of staining
      upon knock-down approaches such as siRNA treatment, c) selectivity of staining in
      immunoblots or immunocytochemistry for the target receptor vs. related subtypes
      when expressed in the same cell line and/or d) antibodies raised against multiple
      distinct epitopes of a receptor yielding very similar staining patterns. Other
      issues of consideration to obtain reliable results based on receptor antibodies
      in applications such as immunohistochemistry or immunoblotting are also being
      discussed.

PMID- 19172249
TI  - Abnormal pain response in pain-sensitive opiate addicts after prolonged
      abstinence predicts increased drug craving.
AB  - RATIONALE: Craving is a primary feature of opiate addiction and is clinically
      significant because of its potential to trigger opiate use and relapse. Opiate
      use can also produce abnormal pain perception. We predicted that for opiate
      addicts (OAs), there may be an association between these two major features of
      addiction (drug craving and abnormal pain responses). OBJECTIVES: To examine pain
      responses in abstinent opiate addicts in comparison with healthy controls using a
      cold-pressor test (CPT) and investigate the correlations of cue-induced drug
      craving with pain responses. MATERIAL AND METHODS: Fifty-four abstinent OAs and
      46 healthy subjects participated in the CPT, and the OAs were also exposed to
      heroin-related cues the day before the pain test. Outcome measures included pain
      tolerance time, VAS ratings of pain intensity and distress, and (in the cue
      exposure procedure) VAS ratings of heroin craving and anxiety. RESULTS: In the
      CPT, abstinent addicts showed shorter pain-tolerance time (85.1 +/- 14.1 s vs.
      133.7 +/- 16.7 s, p < 0.05) and higher ratings of pain distress (61 +/- 3.2 vs.
      45.6 +/- 3.2, p < 0.01) compared to healthy controls. When we divided the addicts
      and controls into pain-sensitive (PS) and pain-tolerant (PT) groups by
      dichotomizing each group in terms of pain-tolerance time, we again found
      differences between the two PS groups (37.3 +/- 3.5 s vs. 57.4 +/- 5.1 s, p <
      0.01 for pain-tolerance time; 66.7 +/- 3.2 vs. 52.4 +/- 3.3, p < 0.01 for
      distress ratings). For all participants, pain-tolerance time was negatively
      correlated with VAS ratings for pain intensity and distress. More importantly,
      the PS addicts reported greater cue-induced craving than the PT addicts (17.8 +/-
      2.2 vs. 4.5 +/- 4.2, p < 0.05). For the addict group as a whole, pain distress
      (the affective aspect of pain) was positively correlated with intensity of cue
      induced craving measured on a different day (r = 0.33, p = 0.01). CONCLUSIONS: A
      hyperalgesic state persists for at least 5 months in abstinent OAs and is
      predictive of cue-induced craving. Longitudinal research is needed to clarify the
      direction of causation between hyperalgesia and opiate addiction.

PMID- 19172251
TI  - Plasma fingerprinting with GC-MS in acute coronary syndrome.
AB  - New biomarkers of cardiovascular disease are needed to augment the information
      obtained from traditional indicators and to illuminate disease mechanisms. One of
      the approaches used in metabolomics/metabonomics for that purpose is metabolic
      fingerprinting aiming to profile large numbers of chemically diverse metabolites
      in an essentially nonselective way. In this study, gas chromatography-mass
      spectrometry was employed to evaluate the major metabolic changes in low
      molecular weight plasma metabolites of patients with acute coronary syndrome (n =
      9) and with stable atherosclerosis (n = 10) vs healthy subjects without
      significant differences in age and sex (n = 10). Reproducible differences between
      cases and controls were obtained with pattern recognition techniques, and
      metabolites accounting for higher weight in the classification have been
      identified through their mass spectra. On this basis, it seems inherently
      plausible that even a simple metabolite profile might be able to offer improved
      clinical diagnosis and prognosis, but in addition, specific markers are being
      identified.

PMID- 19172250
TI  - Effects of alcohol consumption and alcohol expectancy on the categorisation of
      perceptual cues of emotional expression.
AB  - RATIONALE: Evidence that alcohol leads to increased aggressive behaviour is
      equivocal and confounded by evidence that such effects may operate indirectly via
      expectancy. One mechanism by which alcohol consumption may increase aggressive
      behaviour is via alterations in the processing of emotional facial cues.
      OBJECTIVES: We investigated whether acute alcohol consumption or the expectancy
      of consuming alcohol (or both) induces differences in the categorisation of
      ambiguous emotional expressions. We also explored differences between male and
      female participants, using male and female facial cues of emotional expression.
      METHODS: Following consumption of a drink, participants completed a
      categorisation task in which they had to identify the emotional expression of a
      facial stimulus. Stimuli were morphed facial images ranging between unambiguously
      angry and happy expressions (condition 1) or between unambiguously angry and
      disgusted expressions (condition 2). Participants (N = 96) were randomised to
      receive an alcoholic or non-alcoholic drink and to be told that they would
      receive an alcoholic or non-alcoholic drink. RESULTS: Significant effects of
      alcohol were obtained in the angry-disgusted task condition, but only when the
      target facial stimulus was male. Participants tended to categorise male disgusted
      faces as angry after alcohol, but not after placebo. CONCLUSIONS: Our data
      indicate that alcohol consumption may increase the likelihood of an ambiguous but
      negative facial expression being judged as angry. However, these effects were
      only observed for male faces and therefore may have been influenced by the
      greater expectation of aggression in males compared to females. Implications for
      alcohol-associated aggressive behaviour are discussed.

PMID- 19172252
TI  - Determination of diquat by flow injection-chemiluminescence.
AB  - A simple, economic, sensitive and rapid method for the determination of the
      pesticide diquat was described. This new method was based on the coupling of flow
      injection analysis methodology and direct chemiluminescent detection; to the
      authors' knowledge, this approach had not been used up to now with this
      pesticide. It was based on its oxidation with ferricyanide in alkaline medium;
      significant improvements in the analytical signal were achieved by using high
      temperatures and quinine as sensitiser. Its high throughput (144 h(-1)), together
      with its low limit of detection (2 ng mL(-1)), achieved without need of
      preconcentration steps, permitted the reliable quantification of diquat over the
      linear range of (0.01-0.6) microg mL(-1) in samples from different origins
      (river, tap, mineral and ground waters), even in the presence of a 40-fold
      concentration of paraquat, a pesticide commonly present in the commercial
      formulations of diquat.

PMID- 19172253
TI  - Determination of pharmaceuticals in sewage sludge by pressurized liquid
      extraction (PLE) coupled to liquid chromatography-tandem mass spectrometry (LC
      MS/MS).
AB  - In this study, we aimed at optimizing a sensitive and reliable method for a
      simultaneous determination of 31 pharmaceuticals belonging to predominant
      therapeutic classes identified in different types of sewage sludge proceeding
      from conventional and advanced wastewater treatment. Freeze-dried sewage sludge
      was extracted by pressurized liquid extraction technique using accelerated
      solvent extractor Dionex 300. In order to minimize interferences with matrix
      components and to preconcentrate target analytes, solid phase extraction was
      introduced in the method as a clean-up step. The entire method was validated for
      linearity, precision, accuracy, and method detection limits (MDLs). The method
      turned out to be specific, sensitive, and reliable for the analysis of sludge of
      different composition, type, and retention time in the process. The developed
      sample preparation protocol and previously published method for LC-MS/MS analysis
      (Gros et al., Talanta 70:678-690, 2006) were successfully applied to monitor the
      target pharmaceuticals in different types of sewage sludge, i.e., primary sludge,
      secondary sludge, treated sludge, and sludge proceeding from pilot-scale membrane
      bioreactors (MBRs) operating in parallel to the conventional activated sludge
      treatment. Among the investigated pharmaceuticals, 20 were detected in the sludge
      proceeding from full-scale installations, whereas the MBR sludge concentrations
      were below MDLs for several compounds. The highest concentrations were recorded
      for treated and primary sludge. For example, the mean concentration of ibuprofen
      in the digested sludge was 299.3 +/- 70.9 ng g(-1) dw, whereas in the primary
      sludge, it was enriched up to 741.1 ng g(-1) dw. Other pharmaceuticals detected
      at relatively high concentrations were diclofenac, erythromycin, glibenclamide,
      ketoprofen, ofloxacin, azithromycin (up to 380.7, 164.2, 190.7, 336.3, 454.7,
      299.6 ng g(-1) dw in the primary sludge, respectively), gemfibrozil, loratidine,
      and fluoxetine (up to 189.1, 189.7 and 174.1 ng g(-1) dw in the treated sludge,
      respectively).

PMID- 19172254
TI  - Effects of allicin on CYP2C19 and CYP3A4 activity in healthy volunteers with
      different CYP2C19 genotypes.
AB  - OBJECTIVE: To investigate the interaction between allicin and omeprazole and to
      observe the effects of allicin on CYP2C19 and CYP3A4 activity in healthy Chinese
      male volunteers with different CYP2C19 genotypes. METHODS: Eighteen subjects (six
      CYP2C19*1/CYP2C19*1, four CYP2C19*1/CYP2C19*2, two CYP2C19*1/ CYP2C19*3, and six
      CYP2C19*2/ CYP2C19*2) were enrolled in a two-phase randomized crossover trial. In
      each phase, all subjects received placebo or a 180 mg allicin capsule once daily
      for 14 consecutive days. The pharmacokinetics of omeprazole (20 mg orally on day
      15) was determined for up to 12 h following administration by high-performance
      liquid chromatography. RESULTS: In carriers of the CYP2C19*1/CYP2C19*1 and
      CYP2C19*1/CYP2C19*2 or *3 genotype, allicin treatment increased the peak plasma
      concentration (C(max)) of omeprazole by 49.7 +/- 7.2 (p < 0.001) and 54.2 +/-
      9.2% (p < 0.001), and increased the area under the plasma time-concentration
      curve (AUC(0-infinity)) of omeprazole by 48.1 +/- 9.0 (p = 0.001) and 73.6 +/-
      26.7% (p < 0.001), respectively. The ratio of AUC(0-infinity) of 5
      hydroxyomeprazole to omeprazole (a marker for CYP2C19 activity) decreased
      significantly (p < 0.001 and p = 0.001, respectively). However, no
      pharmacokinetic parameters were significantly changed by allicin in
      CYP2C19*2/CYP2C19*2. The C(max) and AUC(0-infinity) of omeprazole sulfone were
      unchanged in all three genotypes. CONCLUSIONS: Allicin reduced the metabolism of
      omeprazole by inhibiting CYP2C19 activity in individuals with the
      CYP2C19*1/CYP2C19*1 and CYP2C19*1/CYP2C19*2 or *3 genotypes, but not in those
      with the CYP2C19*2/ CYP2C19*2 genotype. Allicin did not significantly affect the
      activity of CYP3A4 in all subjects.

PMID- 19172255
TI  - Phase-contrast cine MRI versus MR cisternography on the evaluation of the
      communication between intraventricular arachnoid cysts and neighbouring
      cerebrospinal fluid spaces.
AB  - INTRODUCTION: The objective of this study was to evaluate the role of phase
      contrast cine magnetic resonance imaging (PC-MRI) in detecting possible
      communications between intraventricular arachnoid cysts (IV-ACs) and
      cerebrospinal fluid (CSF) spaces based on MR cisternography (MRC) comparison.
      MATERIALS AND METHODS: Twenty-one patients with IV-AC were examined by PC-MRI and
      MRC. In order to determine the communication of IVAC with its neighbouring CSF
      spaces, PC-MRI was employed. The communication of IV-ACs with the ventricular
      system was examined on at least two anatomic planes. Precontrast images and PC
      MRI were followed by the intrathecal administration of 0.5-1 ml gadopentetate
      dimeglumine. Early and delayed MRC were then carried out. Results of PC-MRI were
      compared with findings of MRC (McNemar's test). RESULTS: In seven IV-ACs, no
      communication was detected by PC-MRI. In 14 IVACs, a pulsatile CSF flow into the
      IV-ACs was observed. All the IV-ACs, which have been determined as non
      communicating (NC) on the PC-MRI, showed NC character on MRC as well. Six cases
      suggesting a communication on PC-MRI showed no communication on MRC. MRC revealed
      eight communicating (38%) and 13 NC (62%) IV-ACs among a total of 21 cases. The
      sensitivity and specificity of PC-MRI imaging in demonstrating the communication
      between the IV-ACs and the CSF were 100% and 54%, respectively. CONCLUSION: PC
      MRI is an effective method for evaluating NC IV-ACs. In order to decide about the
      management of IV-ACs, which are communicating according to the PC-MRI, the
      results should be confirmed with MRC if suspected jet flow is depicted.

PMID- 19172256
TI  - Follow-up study on in-stent thrombosis after carotid stenting using multidetector
      CT angiography.
AB  - INTRODUCTION: The purpose of the present study was to evaluate the role of
      multidetector three-dimensional computed tomography angiography (3D CTA) for
      evaluating both the residual arterial lumen and the sequential change in the
      intraluminal diameter and thrombus formation following carotid artery stenting
      (CAS). MATERIALS AND METHODS: Twenty consecutive patients consisting of 23
      successfully stented carotid arteries were examined by 3D CTA with volume
      rendering at 2, 4, 8, 12 weeks and 6, 12 months of follow-up. RESULTS: The
      eccentric in-stent hypodense area could be detected in ten of 23 (43.5%) carotid
      arteries at 2 weeks of follow-up, and they then gradually declined until they
      almost disappeared at 12 weeks. Eccentric in-stent hypodense areas in the acute
      and subacute phase (up to 12 weeks after CAS) were found in nine out of 16
      carotid arteries with longer stents (3 or 4 cm in size) deployed across the
      carotid bifurcation, whereas no eccentric in-stent hypodense area could be
      observed in the patients with a short stent (2 cm) deployed only to the internal
      carotid artery. Seven of the ten observed eccentric hypodense areas presented on
      the dorsal surface at the carotid bifurcation level. CONCLUSION: Carotid 3D CTA
      for evaluating residual lumen and in-stent thrombus formation after CAS is
      considered to be a useful diagnostic method. To avoid stent occlusion, both the
      acute and subacute phases following CAS (up to 12 weeks) call for the
      administration of appropriate anti-platelet therapy and careful observations of
      the patients.

PMID- 19172257
TI  - Cavernous sinus thrombosis secondary to sinusitis: a rare and life-threatening
      complication.

PMID- 19172258
TI  - Possible mechanisms of rapid neurological deterioration and acute hydrocephalus
      in drug abusers.

PMID- 19172259
TI  - Role of intracellular domains in the function of the herg potassium channel.
AB  - The functional role of the large intracellular regions (which include the cyclic
      nucleotide binding domain, cNBD, and the Per-Arnt-Sim domain, PAS) in the herg
      channel is not well understood. We have studied possible interactions of the cNBD
      with other parts of the channel protein using lysine mutations to disrupt such
      interactions. Some lysine mutations caused significant right shifts in the
      voltage dependence of inactivation; almost all the mutants caused speeding up of
      deactivation time course. In a homology model of the cNBD, lysine mutations that
      affected both inactivation and deactivation lie in a hydrophobic band on the
      surface of the structure of this domain. Some known mutations in the Long QT
      Syndrome type 2, with effects on deactivation, are located at residues close to
      hydrophobic bands on the cNBD and the PAS domains. Such bands of residues in
      these intracellular domains may play an important part in channel function.

PMID- 19172260
TI  - Study of kinetics of thermal aggregation of mitochondrial aspartate
      aminotransferase by dynamic light scattering: protective effect of alpha
      crystallin.
AB  - Thermal aggregation of aspartate aminotransferase from pig heart mitochondria
      (mAAT) has been studied at various temperatures and various protein
      concentrations by dynamic light scattering. The character of the dependence of
      protein aggregate size on time indicates that aggregation of mAAT proceeds in the
      regime of diffusion-limited cluster-cluster aggregation. Suppression of mAAT
      aggregation by alpha-crystallin is due to transition of the aggregation process
      into the regime of reaction-limited cluster-cluster aggregation. Realization of
      this regime of aggregation means that the sticking probability for the colliding
      particles is less than unity.

PMID- 19172261
TI  - Roles of surface residues of intracellular domains of heag potassium channels.
AB  - Ether-a-go-go potassium channels have large intracellular regions containing 'Per
      Ant-Sim' (PAS) and cyclic nucleotide binding (cNBD) domains at the N- and C
      termini, respectively. In heag1 and heag2 channels, recent studies have suggested
      that the N- and C-terminal domains interact, and affect activation properties.
      Here, we have studied the effect of mutations of residues on the surfaces of PAS
      and cNBD domains. For this, we introduced alanine and lysine mutations in heag1
      channels, and recorded currents by two-electrode voltage clamp. In both the PAS
      domain and the cNBD domain, contiguous areas of conserved residues on the
      surfaces of these domains were found which affected the activation kinetics of
      the channel. Next, we investigated possible effects of mutations on domain
      interactions of PAS and cNBD proteins in heag2 by co-expressing these domain
      proteins followed by analysis with native gels and western blotting. We found
      oligomeric association between these domains. Mutations F30A and A609K (on the
      surfaces of the PAS and cNBD domains, respectively) affected oligomeric
      compositions of these domains when proteins for PAS and cNBD domains were
      expressed together. Taken together, the data suggest that the PAS and cNBD
      domains form interacting oligomers that have roles in channel function.

PMID- 19172262
TI  - Enhancement of the microbial community biomass and diversity during air sparging
      bioremediation of a soil highly contaminated with kerosene and BTEX.
AB  - In order to obtain insights in complexity shifts taking place in natural
      microbial communities under strong selective pressure, soils from a former air
      force base in the Czech Republic, highly contaminated with jet fuel and at
      different stages of a bioremediation air sparging treatment, were analyzed. By
      tracking phospholipid fatty acids and 16S rRNA genes, a detailed monitoring of
      the changes in quantities and composition of the microbial communities developed
      at different stages of the bioventing treatment progress was performed. Depending
      on the length of the air sparging treatment that led to a significant reduction
      in the contamination level, we observed a clear shift in the soil microbial
      community being dominated by Pseudomonads under the harsh conditions of high
      aromatic contamination to a status of low aromatic concentrations, increased
      biomass content, and a complex composition with diverse bacterial taxonomical
      branches.

PMID- 19172263
TI  - Gene cloning, expression, and characterization of a novel trehalose synthase from
      Arthrobacter aurescens.
AB  - Trehalose synthase (TreS) is an intramolecular transglycosylase. It specially
      catalyzes the conversion of maltose and trehalose. In this study, a novel treS
      gene, which had a length of 1,797 bp and encoded 598 amino acids, was cloned from
      Arthrobacter aurescens CGMCC 1.1892 and expressed in Escherichia coli. Thin layer
      chromatography results indicated that it could catalyze the conversion between
      maltose and trehalose in one step. However, the ion chromatography results showed
      that, as a byproduct, about 13% glucose was also produced. The purified
      recombinant enzyme had a molecular weight of 68 kDa and showed its optimal
      activity at 35 degrees C and pH 6.5. This enzyme was not thermostable, and its
      activity was increased by 1 mM Mg2+, Mn2+, and Ca2+ while strongly inhibited by 5
      mM Cu2+ and SDS.

PMID- 19172264
TI  - 5-Fluorouracil reduces biofilm formation in Escherichia coli K-12 through global
      regulator AriR as an antivirulence compound.
AB  - The uracil analog, 5-fluorouracil (5-FU), reduces virulence and biofilm formation
      for Pseudomonas aeruginosa PA14 without affecting its growth. As 5-FU is an
      approved anticancer drug, its antivirulence attributes in P. aeruginosa prompted
      us to examine the effect of this compound on three different Escherichia coli K
      12 strains and its effect on virulence genes in E. coli O157:H7 (EHEC); the
      mechanism by which it functions was also examined. 5-FU decreased biofilm
      formation in a dose-dependent manner in E. coli K-12 and repressed the expression
      of virulence genes in EHEC. Five other uracil analogs were also tested for their
      effects on biofilm formation, and none of these compounds affected the biofilm
      formation in E. coli K-12. Whole-transcriptome analysis revealed that 5-FU
      induced the expression of 157 genes and repressed the expression of 19 genes.
      Biofilm formation with the addition of 5-FU was checked in 21 isogenic knockout
      mutants whose gene expression was induced in the microarray data; we found that 5
      FU does not decrease biofilm formation of the cells that lack AriR, a global DNA
      regulator that controls acid resistance in E. coli. Hence, 5-FU represses biofilm
      formation of E. coli K-12 through AriR and is a novel antivirulence compound for
      this strain.

PMID- 19172265
TI  - Characterization of a ring-hydroxylating dioxygenase from phenanthrene-degrading
      Sphingomonas sp. strain LH128 able to oxidize benz[a]anthracene.
AB  - Sphingomonas sp. strain LH128 was isolated from a polycyclic aromatic hydrocarbon
      (PAH)-contaminated soil using phenanthrene as the sole source of carbon and
      energy. A dioxygenase complex, phnA1fA2f, encoding the alpha and beta subunit of
      a terminal dioxygenase responsible for the initial attack on PAHs, was identified
      and isolated from this strain. PhnA1f showed 98%, 78%, and 78% identity to the
      alpha subunit of PAH dioxygenase from Novosphingobium aromaticivorans strain
      F199, Sphingomonas sp. strain CHY-1, and Sphingobium yanoikuyae strain B1,
      respectively. When overexpressed in Escherichia coli, PhnA1fA2f was able to
      oxidize low-molecular-weight PAHs, chlorinated biphenyls, dibenzo-p-dioxin, and
      the high-molecular-weight PAHs benz[a]anthracene, chrysene, and pyrene. The
      action of PhnA1fA2f on benz[a]anthracene produced two benz[a]anthracene
      dihydrodiols.

PMID- 19172266
TI  - Paclitaxel production using co-culture of Taxus suspension cells and paclitaxel
      producing endophytic fungi in a co-bioreactor.
AB  - The co-culture of the suspension cells of Taxus chinensis var. mairei and its
      endophytic fungi, Fusarium mairei, in a 20-L co-bioreactor was successfully
      established for paclitaxel production. The co-bioreactor consists of two-unit
      tanks (10 L each) with a repairable separate membrane in the center, culturing
      Taxus suspension cells in one tank and growing fungi in another. By optimizing
      the co-culture conditions, there was a desirable yield of paclitaxel in Taxus
      cell cultures. The Taxus cell cultures by co-culture produced 25.63 mg/L of
      paclitaxel within 15 days; it was equivalent to a productivity of 1.71 mg/L per
      day and 38-fold higher than that by uncoupled culture (0.68 mg/L within 15 days).
      The optimum conditions for co-culture in the co-bioreactor were: B5 medium,
      inoculating fungi when Taxus cells had grown for 5 days in the co-bioreactor,
      hydrophilic separate membrane in the center of the co-bioreactor, and air flow
      rate of 1:0.85 v/v/m in fungus cultures.

PMID- 19172267
TI  - Testing for radioligand sensitivity to endogenous neurotransmitter release.

PMID- 19172268
TI  - Kinetic models for analysing myocardial [(11)C]palmitate data.
AB  - PURPOSE: [(11)C]Palmitate PET can be used to study myocardial fatty acid
      metabolism in vivo. Several models have been applied to describe and quantify its
      kinetics, but to date no systematic analysis has been performed to define the
      most suitable model. METHODS: In this study a total of 21 plasma input models
      comprising one to three compartments and up to six free rate constants were
      compared using statistical analysis of clinical data and simulations. To this
      end, 14 healthy volunteers were scanned using [(11)C]palmitate, whilst myocardial
      blood flow was measured using H(2)(15)O. RESULTS: Models including an oxidative
      pathway, representing production of (11)CO(2), provided significantly better fits
      to the data than other models. Model robustness was increased by fixing efflux of
      (11)CO(2) to the oxidation rate. Simulations showed that a three-tissue
      compartment model describing oxidation and esterification was feasible when no
      more than three free rate constants were included. CONCLUSION: Although further
      studies in patients are required to substantiate this choice, based on the
      accuracy of data description, the number of free parameters and generality, the
      three-tissue model with three free rate constants was the model of choice for
      describing [(11)C]palmitate kinetics in terms of oxidation and fatty acid
      accumulation in the cell.

PMID- 19172270
TI  - The European searchable tumour line database.
AB  - The European Searchable Tumour line Database (ESTDAB) (
      http://www.ebi.ac.uk/ipd/estdab ) is a freely available and fully searchable
      database of melanoma-derived cell lines, which have been characterised for over
      250 immunologically relevant markers by a consortium of European scientists. The
      database is linked to a cell bank, which can provide melanoma cell lines to non
      profit investigators for a nominal handling charge. All cells are fully HLA typed
      at the genomic and surface expression levels. The expression of a number of
      surface antigens, apoptotic markers, tumour-associated antigens and extracellular
      matrix proteins has also been determined. Cytokine secretion has been tested and
      polymorphisms in cytokine genes have been identified. Glycans at the cell surface
      were identified and glycosyltransferase activity quantified. Cell lines with a
      particular constellation of these parameters can be sought online via the ESTDAB
      interface, which is included as part of the Immuno-Polymorphism Database (IPD)
      section of the European Bioinformatics Institute's (EBI) website.

PMID- 19172271
TI  - Metastatic tumour cells favour the generation of a tolerogenic milieu in tumour
      draining lymph node in patients with early cervical cancer.
AB  - OBJECTIVE: We compared the immune system state in metastatic tumour draining
      lymph nodes (mTDLN) and metastasis free TDLN (mfTDLN) in 53 early stage cervical
      cancer patients to assess whether the presence of metastatic tumour cells worsen
      the balance between an efficacious anti-tumour and a tolerogenic
      microenvironment. METHODS: The immune system state was measured by
      immunophenotypic and functional assessment of suppressor and effector immune cell
      subsets. RESULTS: Compared to mfTDLN, mTDLN were significantly enriched in
      CD4(+)Foxp3(+) regulatory T cells (Treg), which, in addition, exhibited an
      activated phenotype (HLA-DR(+) and CD69(+)). Treg in mTDLN were also
      significantly enriched in neuropilin-1 (Nrp1) expressing cells, a subset
      particularly potent in dampening T cell responses. mTDLN tended to be enriched in
      a population of CD8(+)Foxp3(+)T cells (operationally defined as CD8(+)Treg) that
      showed a suppressor potency similar to Treg under the same experimental
      conditions. Plasmacytoid dendritic cells (pDC) and myeloid DC (mDC) generally
      show distinct roles in inducing T cell tolerance and activation, respectively. In
      line with the excess of suppressor T cells, the ratio pDC to mDC was
      significantly increased in mTDLN. Immunohistochemical testing showed that
      metastatic tumour cells produced the vascular endothelial growth factor, a
      natural ligand for Nrp1 expressed on the cell surface of Nrp1(+)Treg and pDC, and
      therefore a potential mediator by which tumour cells foster immune privilege in
      mTDLN. Consistent with the overall tolerogenic profile, mTDLN showed a
      significant Tc2 polarisation and tended to contain lower numbers of
      CD45RA(+)CD27(-) effector memory CD8(+)T cells. CONCLUSIONS: The increased
      recruitment of suppressor type cells concomitant with the scarcity of cytotoxic
      type cells suggests that in mTDLN the presence of tumour cells could tip the
      balance against anti-tumour immune response facilitating the survival of
      metastatic tumour cells and possibly contributing to systemic tolerance.

PMID- 19172269
TI  - Is the lung scan alive and well? Facts and controversies in defining the role of
      lung scintigraphy for the diagnosis of pulmonary embolism in the era of MDCT.
AB  - PURPOSE: The last decade has seen a changing pattern of utilization of
      multidetector CT (MDCT) versus lung perfusion scintigraphy in the investigation
      of pulmonary venous thromboembolism (VTE). In response to this the International
      Atomic Energy Agency (IAEA) determined that the subject required an overview.
      METHOD: The IAEA has invited a group of five specialists in the relevant fields
      to review the current status and optimum role of scintigraphy, to explore some of
      the facts and controversies surrounding the use of both modalities and to make
      recommendations about the continued role of nuclear medicine for the
      investigation of pulmonary embolism. This paper identifies the relative merits of
      each technique, highlights benefits, focuses on complementary roles and seeks a
      nonadversarial symbiosis. CONCLUSION: The consultants reached a consensus that
      the continued use of scintigraphy for diagnosis of thromboembolic disease is
      recommended, particularly in scenarios where scintigraphy confers specific
      benefits and is complementary to MDCT.

PMID- 19172272
TI  - Autologous hematopoietic stem cell transplantation in adult acute lymphoblastic
      leukemia: still not out of fashion.
AB  - The role of autologous hematopoietic stem cell transplantation (autoHSCT) in
      adult acute lymphoblastic leukemia (ALL) is still unclear. We retrospectively
      analyzed the results of the autoHSCT and maintenance therapy, with oral 6
      mercaptopurine and methotrexate, in comparison to conventional-dose chemotherapy
      in the consolidation treatment of adult ALL and lymphoblastic lymphoma (LBL). The
      patients, with HLA identical sibling donor, underwent allogeneic transplantation,
      while the others were treated with autoHSCT and maintenance therapy with oral 6
      mercaptopurine and methotrexate, or by conventional-dose chemotherapy (patient's
      decision, no autologous hematopoietic stem cells harvest). Sixty consecutive
      adult patients (median age 35.2 years; range 17.3 to 70.7) with ALL (n = 52), LBL
      (n = 7), and acute biphenotypic leukemia (n = 1) were treated in our center from
      1997 to 2007. Patients treated with chemotherapy alone (n = 35) had a shorter
      median progression-free survival (PFS) compared to patients who underwent
      autoHSCT plus maintenance therapy (n = 18), 8.4 and 46.8 months, respectively (p
      = 0.017). Patients treated with chemotherapy alone had also a shorter median
      overall survival (OS) compared to patients treated with autoHSCT: 13.0 vs. 46.8
      months (p = 0.046). The differences remained statistically significant even after
      excluding patients with Ph positivity. We can conclude that, in our case,
      autoHSCT followed by maintenance chemotherapy is a good option for adult patients
      with ALL and, in standard-risk and high-risk patients, provides more favorable OS
      and PFS rates compared to patients treated by chemotherapy alone. However, we are
      aware of the fact that our analysis may have been distorted by the fact that the
      analysis is retrospective, that treatment with autoHSCT was based on patient's
      decision, and that chemotherapy may have been administered to negatively selected
      patients.

PMID- 19172273
TI  - Antitumor effects of polyclonal antithymocyte globulins: focus on B-cell
      malignancies and multiple myeloma.
AB  - Polyclonal antithymocyte globulins (ATGs) are used in organ and allogeneic stem
      cell transplantation mainly due to their immunomodulatory potential. Since ATGs
      contain antibodies against antigens expressed on various hematopoetic cells, it
      is not surprising that they induce cell death not only in healthy T-, B-, NK, and
      dendritic cells but also in malignant cells of lymphatic and to a lesser extent
      of myeloid lineage. The cytotoxic and antiproliferative effects of ATGs in
      malignant B-cells have been known for many years, without attracting clinical
      attention due to the advent of monoclonal antibodies like rituximab. Recent data
      indicate a potential role of ATGs in the therapy of multiple myeloma, a disease
      in which monoclonal serotherapy has been rather unsuccessful. This review
      discusses available data demonstrating the cytotoxic effects of ATGs and
      envisages a possible new role of these polyclonal antibodies in the therapy of
      hematological malignancies.

PMID- 19172274
TI  - Risk factors for poor treatment outcome and central nervous system relapse in
      diffuse large B-cell lymphoma with bone marrow involvement.
AB  - Although several studies have described the prognostic implication of bone marrow
      (BM) involvement (BMI) in lymphoma, studies focused on BM-involved diffuse large
      B-cell lymphoma (DLBCL) are very rare and small-sized. This study was performed
      to examine the prognostic impact of morphologic findings of BMI by lymphoma and
      risk factors for central nervous system (CNS) relapse in BM-involved DLBCL.
      Between 1993 and 2005, 675 patients were diagnosed with DLBCL, and 88 patients
      who had BMI at initial diagnosis were eligible for this study. The median overall
      survival (OS) and failure-free survival (FFS) of 88 patients were 36.6 and 20.1
      months, respectively. When three variables from BM morphologic findings (the
      pattern of BM infiltration, extent of BMI by lymphoma, and percentage of large
      cells in the infiltrate) were simultaneously included into multivariate model,
      the increased extent of BMI by lymphoma (> or =10%) in BM area was the only
      negative prognostic factor, independent of the International Prognostic Index
      (IPI). Patients with both lower IPI scores and less extent of BMI showed an
      excellent prognosis with chemotherapy alone (5-year OS and FFS rates, 80% and
      69%). However, morphologic BM features were not independent predictive factors
      for CNS recurrences. An increased lactate dehydrogenase (LDH) level at initial
      diagnosis was the only independent predictive factor for CNS relapse. Further
      efforts should be directed toward finding optimal treatment modalities based on
      the IPI and the extent of BMI by lymphoma. CNS prophylaxis may be considered only
      in patients with initial elevated LDH levels.

PMID- 19172275
TI  - Wegener's granulomatosis complicated by central diabetes insipidus and peripheral
      neutrophy with normal pituitary in a patient.
AB  - Wegener's granulomatosis (WG) is a necrotizing systemic vasculitis that any organ
      system can be involved in. We report a patient who was hospitalized with
      recurrent nodules in pulmonary computed tomograph and symptoms such as
      intermitted fever, polydipsia, insensibility and pain on extremities. Laboratory
      investigation showed positive antineutrophil cytoplasmic antibody in a
      cytoplastic pattern. The histopathologic result of the lung nodule revealed
      multiloci necrosis of lung tissue accompanied with large amount of neutrophils.
      She was diagnosed as WG with multi-systemic involvements and almost recovered on
      6 months' prednisone and cyclophosphamide treatment.

PMID- 19172276
TI  - Relationship between spinal mobility measures and quality of life in patients
      with ankylosing spondylitis.
AB  - The aim of this study was to assess spinal mobility status and Quality of life
      (QoL) of patients with ankylosing spondylitis (AS) and determine the relationship
      between spinal mobility and measures of clinical condition including QoL. A total
      of 74 patients with AS were included in this study. Disease specific instruments
      Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Disease
      Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI)
      were applied, and mobility testing: occiput-wall distance and chest expansion.
      QoL was assessed by the Short Form-36 (SF-36). The mean age was 48.5 years; there
      were significant correlations between BASMI score and age (P < 0.001), disease
      duration (P < 0.001), symptoms duration (P < 0.001) and BASFI (P < 0.001). BASMI
      was negatively correlated with SF-36 physical function subscale (P < 0.001) and
      general health subscale (P = 0.029). In multivariate regression analysis, BASFI
      score (P < 0.001) was independently associated factor with physical function
      domain of SF-36. This study showed that in AS spinal mobility measures are
      associated with physical function, general health, emotional role and mental
      health domains of QoL.

PMID- 19172278
TI  - Diagnostic performance of diffusion-weighted magnetic resonance imaging in
      esophageal cancer.
AB  - The purpose of this study was to assess the value of diffusion-weighted magnetic
      resonance imaging (DWI) in detecting esophageal cancer and assessing lymph-node
      status, compared with histopathological results. DWI was prospectively performed
      in 24 consecutive patients with esophageal cancer, using the diffusion-weighted
      whole-body imaging with background body signal suppression (DWIBS) sequence.
      DWIBS images were fused with T2-weighted images, and independently and blindly
      evaluated by three board-certified radiologists, regarding primary tumor
      detectability and lymph-node status. Apparent diffusion coefficients (ADCs) of
      the primary tumor and lymph nodes were also measured. Average primary tumor
      detection rate was 49.4%, average patient-based sensitivity and specificity for
      the detection of lymph-node metastasis were 77.8 and 55.6%, and average lymph
      node group-based sensitivity and specificity were 39.4 and 92.6%. There were no
      interobserver differences among the three readers (P < 0.0001). Mean ADC of
      detected primary tumors was 1.26 +/- 0.29x10(-3) mm(2)/s. Mean ADC of metastatic
      lymph nodes (1.46 +/- 0.35x10(-3) mm(2)/s) was significantly higher (P < 0.0001)
      than that of nonmetastatic lymph nodes (1.15 +/- 0.24 mm(2)/s), but ADCs of both
      groups overlapped. In conclusion, this study suggests that DWI only has a limited
      role in detecting esophageal cancer and nodal staging.

PMID- 19172280
TI  - Colonic manifestation of mantle cell lymphoma with multiple lymphomatous
      polyposis.

PMID- 19172279
TI  - Plasminogen fragment K1-3 inhibits expression of adhesion molecules and
      experimental HCC recurrence in the liver.
AB  - PURPOSE: There is no established adjuvant or neo-adjuvant treatment to curb tumor
      recurrence of hepatocellular carcinoma (HCC). Recent data showed that angiostatic
      factors can inhibit tumor cell adhesion to the endothelium and therefore
      recurrence/metastasis. We tested a potential preventive, pre-operative strategy
      using plasminogen kringles 1-3 (K1-3) to overcome this hurdle. MATERIALS AND
      METHODS: Effects of K1-3 on the intercellular cell adhesion molecule (ICAM) and
      vascular cell adhesion molecule (VCAM) expression was analyzed in vitro and in
      vivo on RNA and protein levels. Influence of K1-3 on HCC recurrence in the liver
      was analyzed in an orthotopic tumor model. RESULTS: K1-3 decreased ICAM
      expression in Hepa129 tumor cells and VCAM expression in SVEC4-10 endothelial
      cells in vitro. In vivo, ICAM was reduced in histological tumor sections.
      Preventive treatment with AdK1-3 inhibited experimental HCC recurrence and tumor
      growth in the liver. CONCLUSIONS: We were able to show that K1-3 inhibits
      intrahepatic tumor recurrence. This novel aspect elucidates a possible approach
      to prevent HCC recurrence.

PMID- 19172281
TI  - Chronic inflammatory demyelinating polyradiculoneuropathy associated with
      inflammatory bowel diseases: questioning the autoimmunity hypothesis.

PMID- 19172282
TI  - Effects of amniotic membrane on the healing of primary colonic anastomoses in the
      cecal ligation and puncture model of secondary peritonitis in rats.
AB  - PURPOSE: We aimed to investigate the effects of amniotic membrane on primary
      colonic anastomoses in a rat peritonitis model. MATERIALS AND METHODS: Fifty
      female Sprague Dawley rats were used in the study. Bacterial peritonitis was
      induced in all rats by performing a cecal ligation and puncture. Ten rats served
      as controls for the bursting pressure measurement, while the other 40 animals
      were divided into two groups (the anastomosis group (P) or the amniotic membrane
      group (PA)), and all of them underwent colonic anastomosis. The latter group had
      amniotic membrane covering their anastomoses. Half of the PA and P groups were
      sacrificed on the third postoperative day (PA3, P3), and the other half on the
      seventh postoperative day (PA7, P7). RESULTS: The bursting pressures were
      significantly higher in groups PA3 and PA7 compared with P3 (p < 0.01) and P7 (p
      < 0.05), respectively. Inflammatory cell infiltration and adhesion scores were
      significantly lower in groups PA3 and PA7 compared with groups P3 (p < 0.001, p <
      0.01, respectively) and P7 (p < 0.001, p < 0.05, respectively). Neoangiogenesis,
      fibroblast activity, collagen deposition, and hydroxyproline concentrations were
      significantly higher in groups with amniotic membrane than in groups without
      amniotic membrane (p < 0.05, for all comparisons). CONCLUSION: This study showed
      that the covering of colonic anastomoses with amniotic membrane significantly
      prevented the delaying effect of intraperitoneal sepsis and provided a safer and
      stronger anastomosis than suture and that this was the case for both the early
      and late phases of anastomotic healing in the colon.

PMID- 19172283
TI  - Meta-analysis of medical treatment and placebo treatment for preventing
      postoperative recurrence in Crohn's disease (CD).
AB  - INTRODUCTION: We performed a meta-analysis to compare the clinical and endoscopic
      recurrence of medical treatment and placebo treatment for preventing
      postoperative recurrence in Crohn's disease. MATERIALS AND METHODS: Trials were
      located through Medline, Embase, the Cochrane Central Register of Controlled
      Trials, Ovid, Sciencedirect, and Ingenta electronic databases. From 124 articles
      screened, 14 were identified as randomized placebo-controlled trials and were
      included for data extraction. Main outcome measures were clinical recurrence,
      endoscopic recurrence, and severe endoscopic recurrence. The meta-analysis was
      performed with the fixed-effects model. RESULT: Fourteen studies with 1,497
      participants were analyzed. In the intention-to-treat analysis, medical treatment
      was associated with a significantly lower incidence of clinical recurrence
      (relative risk of 0.74, 95% confidence interval 0.64-0.87, P = 0.000], but there
      were no significant differences in endoscopic recurrence (0.94, 0.83-1.07, P =
      0.353) and severe endoscopic recurrence (0.83, 0.60-1.16, P = 0.281) between the
      two groups. When using per-protocol analysis, the results is similar, medical
      treatment was associated with a significantly lower incidence of clinical
      recurrence (0.84, 0.72-0.97, P = 0.020), but there were no significant
      differences in endoscopic recurrence (0.94, 0.85-1.05, P = 0.268) or severe
      endoscopic recurrence (0.76, 0.55-1.04, P = 0.084) between the two groups of
      patients. CONCLUSIONS: Medical treatment has a sufficiently beneficial effect on
      decreasing the risk of clinical postoperative recurrence in patients with CD.

PMID- 19172285
TI  - Low cost polymer intramedullary nails for fracture fixation: a biomechanical
      study in a porcine femur model.
AB  - INTRODUCTION: Whilst intramedullary nailing is a commonly accepted technique for
      lower limb fracture fixation, the cost of nails can be prohibitive in hospitals
      in developing nations. In these institutions bone cement has found many off label
      applications, that whilst are effective do not meet manufacturers guidelines. The
      aim of this study was to examine the biomechanics of one such application,
      fracture fixation using a bone cement intramedullary nail. MATERIALS AND METHODS:
      Five porcine femurs underwent a mid-shaft osteotomy and were fixed using a nail
      made from antibiotic simplex bone cement. The torsional and flexural stiffness
      and shear modulus of these constructs were compared to five intact porcine
      femurs. RESULTS: The bone cement intramedullary nail was able to achieve relative
      stability in both torsion, with a mean shear modulus of 0.17 GPa and in flexion
      with a mean flexural stiffness of 358 N/mm. This corresponds to 47 and 22% of the
      respective measurements in the intact femurs. The mean ultimate flexural strength
      of fracture/nail constructs was 936 +/- 350 N, which is 20% of the ultimate
      flexural strength of an intact porcine femur (4,820 +/- 698 N). CONCLUSION:
      Intramedullary nails made from bone cement were able to provide sufficient
      promise in this situation to warrant further investigation for their
      applicability as a low cost alternative for use in developing countries.

PMID- 19172284
TI  - Long-term success rate after surgical treatment of anorectal and rectovaginal
      fistulas in Crohn's disease.
AB  - BACKGROUND: Due to the considerable variety in the clinical presentation of
      anorectal and rectovaginal fistulas in Crohn's disease, data on treatment results
      for each type of fistula are limited. The aim of this study was to summarize the
      results after surgical treatment of such fistulas in a large consecutive series
      of patients. PATIENTS AND METHODS: All patients with anorectal or rectovaginal
      fistula due to Crohn's disease requiring surgery in our institution between 1991
      and 2001 were extracted from a prospective database. A standardized telephone
      interview was conducted and patients were followed in our outpatient clinic, the
      department of internal medicine, or at their gastroenterologist. Type of fistula
      and interventions were classified and analyzed. Recurrence-free time intervals
      were estimated for each type of fistula and for the different surgical
      procedures. The influence of the surgical procedure, the number of operations
      performed, and the correlation to other localizations of the disease were
      analyzed in regard to the recurrence rate. RESULTS: From 777 patients with
      Crohn's disease undergoing surgery between 1991 and 2001, 147 had anorectal or
      rectovaginal fistula (292 operations). Ninety-eight percent of them also had
      Crohn's disease in the colon or rectum compared to only 21% of patients without a
      fistula (p value <0.001). Over long-term follow-up, 29 patients (20%) required
      proctectomy. Submucosal fistulas needed major surgery in only 14% of cases
      compared to 56% of cases with rectovaginal fistulas. After 5 years, complex
      fistulas showed a strong trend towards a higher recurrence rate after surgery
      than simple submucosal fistulas (45.6% vs. 18.8%, p = 0.079). Whereas recurrences
      occurred over the whole observation period in the group of patients with complex
      fistulas, there was no further recurrence in patients with submucosal fistulas 13
      months after surgery. In rectovaginal fistulas, additional levatorplasty showed
      no advantage over standard endorectal advancement flap. CONCLUSIONS: Long-term
      follow-up demonstrates that recurrence rates after repair of complex fistulas for
      Crohn's disease are high and continuously increase over time. Submucosal fistulas
      have the best outcome; after 13 months without recurrence, definite cure can be
      expected.

PMID- 19172286
TI  - The accuracy and precision of computer assisted surgery in the assessment of
      frontal plane deviations of the lower extremity: a femoral fracture model.
AB  - OBJECTIVES: Mechanical axis deviation of the lower extremity as a result of
      malreduction or malunion of fractures plays an important role in the development
      of arthritis. Therefore it is crucial to restore the limb alignment as accurate
      as possible. The purpose of this study was to evaluate the accuracy and precision
      of navigation in assessing isolated frontal plane (varus/valgus) deviations of
      the lower limb in a simulated fracture model of the femur. MATERIALS AND METHODS:
      Three fracture models with ten specimens in each were created in femoral
      synthetic composite bones to simulate a subtrochanteric (AO/OTA 31-A1), mid
      diaphyseal (AO/OTA 32-A3), and supracondylar (AO/OTA 33-A1) femur fracture. Each
      specimen was mounted on a custom holding device and registered with the
      navigation system. Eight custom-made aluminum wedges of varying angles (5 degrees
      -26 degrees ) were used to create varus/valgus angulations at the fracture site.
      After wedge placement, the frontal plane deformity was recorded and registered by
      the navigation system. The means and standard deviations for each navigated wedge
      angle were calculated and compared to the actual wedge angle using a one sample t
      test. A single factor ANOVA test was subsequently performed to see if the
      differences between the navigated mean angles in each fracture group were
      statistically significant. The level of significance was defined as P < 0.05.
      RESULTS: None of the navigated mean angles were found to be significantly
      different from the actual wedge angles (P = 0.05-1.00). More specifically, the
      differences between the navigated mean angles and the actual wedge angles ranged
      from 0 degrees to 0.7 degrees . Furthermore, the differences between the
      navigated mean angles in each angle group were found to be statistically
      insignificant (P = 0.53-0.99). CONCLUSION: The high accuracy and precision of
      navigation systems in determining frontal plane deformities of long bones can
      make them an invaluable tool for the exact reduction and realignment of lower
      extremity fractures.

PMID- 19172288
TI  - Visual outcomes of vitreoretinal surgery in eyes with severe open-globe injury
      presenting with no-light-perception vision.
AB  - BACKGROUND: Severe ocular trauma causing no light perception (NLP) typically
      carries a dismal prognosis, and implies no further therapeutic intervention. We
      have identified a cohort of patients with verified NLP following open-globe
      injury who have recovered vision of light perception (LP) or better. We evaluated
      the outcomes of vitreoretinal surgery performed on eyes that were NLP post open
      globe injury. METHODS: Retrospective review of outcomes of secondary
      vitreoretinal surgery performed at Massachusetts Eye and Ear Infirmary from 1
      January 2001 to 31 December 2006 on all cases of open-globe repair (OGR) that had
      NLP prior to OGR or on the first post-operative day. RESULTS: A total of 648
      cases of OGR were performed in the study period. Eighty-eight patients had NLP
      prior to OGR or on the first post-operative day after OGR. Twenty-three patients
      from the above group (26.1%) spontaneously recovered a vision of light perception
      (LP) or better. Eight of the 23 patients had a secondary vitreoretinal surgery.
      All eyes that did not undergo vitreoretinal surgery returned to NLP or became
      phthisical within 7 months. Among the eight eyes that underwent surgery, five had
      improvement, with vision ranging from hand motion to 20/70. Prognostic indicators
      for successful surgical outcome were hand motion or better vision prior to
      vitreoretinal surgery, recovery of vision within 5 days of OGR, and vitreoretinal
      intervention within 5 weeks of the initial open-globe injury. CONCLUSION:
      Patients with severe open-globe injury and NLP occasionally recover LP or better
      vision. These patients may regain useful vision after vitreoretinal surgery if
      prompt referral and intervention is attempted and if the spontaneous visual
      recovery occurs within the first week after OGR.

PMID- 19172289
TI  - Virtual reality training improves wet-lab performance of capsulorhexis: results
      of a randomized, controlled study.
AB  - PURPOSE: To investigate, whether capsulorhexis training on the EYESi surgical
      simulator improves wet-lab operating performance of surgical novices. METHODS:
      Randomized, masked experimental study. Thirty-one medical students and 32
      ophthalmological residents were randomized to either virtual reality (VR)
      training, or control. Initially and after 3 weeks each participant performed
      three capsulorhexis tasks in a porcine wet-lab. In between, participants from the
      VR training groups completed two training trials on the EYESi surgical simulator
      (VRmagic, Mannheim, Germany). VR training consisted of basic skill tasks and
      capsulorhexis tasks of increasing difficulty, and preset performance goals had to
      be reached for each task. All wet-lab procedures (n = 372) were recorded on DVD,
      and assessed by a masked observer. Each wet-lab capsulorhexis was evaluated with
      regard to five criteria (circularity, size, centering, time, tissue protection)
      using a predefined scoring system with a maximum overall score of 10 points (2
      per criterion). The primary outcome measure was the intra-individual difference
      in the average overall performance score between the first and second wet-lab
      capsulorhexis procedures. Ten operation videos were additionally assessed by
      three further investigators to determine interobserver agreement. RESULTS: Inter
      observer agreement regarding the overall performance score was high (ICC = 0.91).
      Compared to control groups, VR-trained students and residents showed significant
      improvement in their median wet-lab capsulorhexis overall performance score
      compared to controls (+3.67 vs +0.33 points, P = 0.001 and +3.33 vs +/-0.00
      points, P < 0.0001). The capsulorhexis performance of VR-trained students and
      residents was also more consistent with a lower standard deviation of scores
      compared to controls (SD 1.3 vs 2.1 and 1.2 vs 1.7 points respectively).
      CONCLUSIONS: Structured capsulorhexis training on the EYESi to reach specific
      target criteria significantly improved wet-lab capsulorhexis performance.

PMID- 19172290
TI  - Implantation of alloplastic material increases survival of mice subsequently
      exposed to polymicrobial sepsis.
AB  - PURPOSE: Major surgery can modulate the immune system and by this the clinical
      course of following complications. Effects of minor surgical treatments on the
      immune system and septic complications are poorly understood. MATERIALS AND
      METHODS: We investigated the effect of a minor surgical procedure--the
      implantation of an osmotic pump--on the outcome of experimental polymicrobial
      sepsis (colon ascendens stent-induced peritonitis, CASP) in mice. RESULTS:
      Animals with pumps implanted 3 days prior to CASP showed an attenuated clinical
      course of sepsis and increased survival. While measured serum cytokine levels
      were not affected by the minor surgical stress of pump implantation, splenocyte
      secretion of IFN-gamma in response to lipopolysaccharide was increased.
      CONCLUSION: The early implantation of alloplastic material modulates the immune
      system and leads to an increased survival of a polymicrobial sepsis. Identifying
      the molecular nature of this effect might point the way to a new therapeutic
      approach to reduce sepsis mortality.

PMID- 19172291
TI  - Over-expression of cathepsin E and trefoil factor 1 in sessile serrated adenomas
      of the colorectum identified by gene expression analysis.
AB  - Sessile serrated adenomas are now recognised as precursor lesions of a
      substantial subset of colorectal cancers arising via a so-called "serrated
      pathway". However, their biological markers remain to be defined. The aim of our
      study was to identify differentially expressed genes in sessile serrated adenomas
      and conventional adenomas. Gene expression analysis demonstrated molecular
      differences between polyp types. Further studies using quantitative real-time
      polymerase chain reaction on cathepsin E (CTSE) demonstrated a significantly (p <
      0.05) higher expression in sessile serrated adenomas as compared to hyperplastic
      polyp and tubular adenomas. Trefoil Factor 1 showed the same trend of expression
      for sessile serrated adenomas as compared to hyperplastic polyps and was
      significantly higher in both polyps compared to tubular adenomas.
      Immunohistochemistry for both proteins demonstrated strong cytoplasmic staining
      of abnormal crypts in all sessile serrated adenomas, while staining in tubular
      adenomas and hyperplastic polyps was absent or weak and focal. BRAF and KRAS
      mutation analysis were employed to further validate polyp discrimination. The
      findings demonstrated the positive association of the BRAF mutation, V600E, with
      sessile serrated adenomas and KRAS mutations with tubular adenomas (p < 0.05).
      This study demonstrates the over-expression in CTSE, in particular, and TFF1 in
      sessile serrated adenomas compared to both hyperplastic polyps and tubular
      adenomas.

PMID- 19172293
TI  - Histological grading in a large series of advanced stage ovarian carcinomas by
      three widely used grading systems: consistent lack of prognostic significance. A
      translational research subprotocol of a prospective randomized phase III study
      (AGO-OVAR 3 protocol).
AB  - While there is no doubt that histologic grading is applicable in early stage
      ovarian carcinoma, it is still in controversial discussion concerning advanced
      stage ovarian carcinoma. It was the aim of this study to assess the three most
      widely used grading systems for ovarian carcinoma in terms of prognostic
      significance, concordance rates, and reproducibility in a large number of
      advanced stage ovarian carcinomas of all types after standardized chemotherapy.
      Representative hematoxylin and eosin slides from 334 cases of stage IIB-IV
      ovarian carcinoma (prospective randomized, multi-center, phase III study) were
      used. The first round was grading of all cases according to FIGO, GOG, and
      Silverberg by one author. The second round (after 1 year) was 30 randomly
      selected cases graded by three authors. None of the three grading systems was
      prognostically significant (FIGO p = 0.38; GOG p = 0.70; Silverberg p = 0.92).
      The concordance rates between the three systems were as follows: FIGO/GOG 95.5%,
      kappa = 0.929; Silverberg/FIGO 69.9%, kappa = 0.533; Silverberg/GOG 66.8%, kappa
      = 0,481. Grading of advanced stage ovarian carcinomas was of no value for
      estimation of prognosis in this homogeneously treated patient group. Alternative
      methods should be defined, which might help to separate patients with high risk
      of tumor progression from others with low risk.

PMID- 19172292
TI  - Complement C3a expression and tryptase degranulation as promising
      histopathological tests for diagnosing fatal amniotic fluid embolism.
AB  - To date, the most recent specific diagnostic investigations for amniotic fluid
      embolism have been unable to conclusively identify any mechanism of disease other
      than a physical block to the circulation. We selected eight fatal cases in
      previously healthy women with uneventful singleton term pregnancies who presented
      to tertiary care centers in Italy for delivery. Pathologic features were assessed
      immunohistochemically using anti-fibrinogen, anti-tryptase, anti-C(3a), and anti
      cytokeratin antibodies. AE1/AE3 cytokeratin stains proved positive, and tryptase
      positive material was documented outside pulmonary mast cells. In all studied
      cases, expression of complement C(3a) was twofold lower than in the control
      group, suggesting a possible complement activation in AFE, initiated by fetal
      antigen leaking into the maternal circulation.

PMID- 19172294
TI  - In vivo anti-malarial effect of the beta-amino alcohol 1t on Plasmodium berghei.
AB  - Glycerol derivatives are a class of compounds, which are easy and inexpensive to
      produce with potent anti-malarial activities against blood stages of Plasmodium
      falciparum in vitro. In the present study, one of these compounds, termed 1t,
      which had the lowest IC(50) values, was assessed in a murine malarial model.
      Nuclear magnetic resonance imaging and Balb/c mice infected with Plasmodium
      berghei ANKA strain were treated in a 4-day suppressive test. Mice received a
      once-daily intraperitoneal administration of 50 mg/Kg of the drug for 4 days.
      Although no parasitaemia clearance was reached, a slower parasite proliferation
      and a slightly longer survival time compared with the placebo group were
      observed.

PMID- 19172295
TI  - Initial characterization of Pf62, a novel protein of Plasmodium falciparum
      identified by immunoscreening.
AB  - In order to find new antigens from Plasmodium falciparum, a complementary DNA
      (cDNA) library was constructed and screened. The study of expression library of
      P. falciparum was performed in an attempt to identify new antigens that could
      have potential relevance for the falciparum-malaria diagnosis and/or protection.
      Between the positive clones detected (ring erythrocyte surface antigen, merozoite
      erythrocyte surface antigen, RHOP H3, CSP, LSA), a new gene that correspond to a
      new protein (Pf62) was isolated and characterized. This antigen was useful for
      the diagnosis of malaria in enzyme-linked immunosorbent assay tests. The cDNA
      corresponding to this antigen and structure of the gene were characterized. Pf62
      is a single copy gene that contains one exon. The Pf62 cDNA has an open reading
      frame of 1,599 nucleotides that code for a putative protein of 532 amino acids
      with a predicted molecular mass of 62 kDa. The polypeptide contains in the
      central section two regions of repeats of 21 and 19 amino acids, respectively.
      The localization of the Pf62 protein was performed by immunoblot, indirect
      immunofluorescence assay and immunoelectron microscopy. Pf62 is localized in the
      cytoplasm of the parasite and also on the surface of the infected erythrocyte.
      Serologic assays by using synthetic peptides designed from different antigenic
      regions of the Pf62 protein resulted in acceptable data of sensitivity and
      specificity in symptomatic malaria patients.

PMID- 19172296
TI  - Angiostrongylus cantonensis: morphological and behavioral investigation within
      the freshwater snail Pomacea canaliculata.
AB  - An infection with Angiostrongylus cantonensis, the main causative agent for human
      eosinophilic encephalitis, can be acquired through the consumption of the
      freshwater snail Pomacea canaliculata. This snail also provides a suitable model
      to study the developmental morphology and behavior of A. cantonensis larvae,
      facilitated by the snail's distinct lung structure. We used microanatomy for
      studying the natural appearance and behavior of A. cantonensis larvae while
      developing within P. canaliculata. The distribution of refractile granules in the
      larval body and characteristic head structures changed during the developmental
      cycle. Two well-developed, rod-like structures with expanded knob-like tips at
      the anterior part were observed under the buccal cavity as early as the late
      second developmental stage. A "T"-shaped structure at the anterior end and its
      tenacity distinguished the outer sheath from that shed during the second molting.
      Early first-stage larvae obtained from fresh rat feces are free moving and
      characterized by a coiled tail, whereas a mellifluous "Q"-movement was the
      behavioral trait of third-stage A. cantonensis larvae outside the host tissue. In
      combination, the distribution of refractive granules, distinct head features,
      variations in sheaths, and behavioral characteristics can be utilized for
      differentiation of larval stages, and for distinguishing A. cantonensis larvae
      from those of other free-living nematodes.

PMID- 19172299
TI  - Acute cyanosis in a child after percutaneous placement of a peritoneal dialysis
      catheter: question. Methemoglobinemia.

PMID- 19172297
TI  - Characterization of tissue distribution and histopathological lesions in Neospora
      caninum experimentally infected gerbils.
AB  - Gerbils (Meriones unguiculatus) were inoculated intraperitoneally (i.p.) with
      Neospora caninum tachyzoites to examine parasite distribution and histological
      lesions at different time points over a 9-day period of infection. Gerbils were
      sacrificed 12 h post-infection (PI), then daily intervals up to day 9 PI. The
      parasite was detected by PCR assay targeting the Nc5 sequence of N. caninum. The
      parasite was not found in any organs until day 5 PI, however, from day 8 PI
      onwards, they were detected in all the organs examined as demonstrated by PCR.
      The first target organs in acute N. caninum infection were liver, spleen, and
      kidney, but not the blood as was expected. Histologic lesions were detected in
      the liver and spleen only, no lesions were found in other organs examined until
      the end of the experiment. Notably, the focal miliary hepatitis was observed in
      the liver of infected gerbils just after 1 day post-inoculation, whereas splenic
      lesions were not found until day 5 PI. These results reinforce the applicability
      of gerbils as a suitable model of acute neosporosis and provide new insights into
      the response of gerbils to N. caninum intraperitoneal infection.

PMID- 19172300
TI  - Chronic kidney disease in the VACTERL association: clinical course and outcome.
AB  - Approximately 60% of VACTERL (vertebral defects, anal atresia, cardiac defects,
      tracheoesophageal fistula with atresia, renal defects/radial limb dysplasia)
      patients have renal anomalies that can be associated with chronic kidney disease
      (CKD). With improved medical care, a large proportion of these patients survive
      into adulthood. Longitudinal follow-up data regarding the management of kidney
      disease in these children is lacking. Twelve VACTERL patients with CKD stage 2-5
      and 12 age-matched controls with similar urologic anomalies and CKD [mean follow
      up period 15.0 +/- 1.4 (SE) and 11.9 +/- 2.1 years, respectively] were identified
      in a single center. Eight VACTERL patients progressed to end-stage renal disease
      (ESRD) compared to four controls (66.7 vs. 33.3%, respectively). Six VACTERL
      patients were dialyzed pre-transplant. Of the four patients on peritoneal
      dialysis (PD), three had to be switched to hemodialysis due to complications,
      whereas two of the three controls on PD did not experience significant problems.
      Seven VACTERL patients underwent renal transplantation compared to four controls.
      Mean creatinine clearance 2 years post-transplant was 65.8 +/- 6.3 in VACTERL
      patients vs. 87.8 +/- 7.1 ml/min per 1.73 m(2) in controls (p = 0.03). VACTERL
      patients had a significantly lower mean height standard deviation score than the
      controls (-2.34 +/- 0.41 vs. -1.27 +/- 0.24, respectively; p < 0.05). Based on
      these results, VACTERL patients with CKD develop ESRD more frequently, experience
      more complications with dialysis, may have a poorer transplant outcome, and have
      more severe growth failure than controls.

PMID- 19172301
TI  - Cervical cancer patient information-seeking behaviors, information needs, and
      information sources in South Korea.
AB  - GOALS: The aim of this study was to explore the cancer information needs,
      utilization, and source preferences in South Korean women with cervical cancer.
      PATIENTS AND METHODS: This was a multicenter descriptive study comprising 968
      cervical cancer patients (stages 0-IVb; mean age, 55 years; response rate, 34.4%
      of those who agreed to participate) who had been treated from 1983 through 2004
      at any of the six South Korean hospitals. The study data were obtained through a
      mail-in self-response questionnaire that asked about the patients' cancer
      information needs, cancer-information-seeking behavior, information sources, and
      type of information needed. It also collected data about anxiety and depression.
      RESULTS: Of the 968 cervical cancer patients, 404 (41.7%) had sought cancer
      information. When patients felt a need for information, their information-seeking
      behavior increased (overall risk = 4.053, 95% confidence interval = 2.139-7.680).
      Television and/or radio were the most frequently cited sources, and narratives
      about cancer experiences were the most easily understood forms of cancer
      information. More younger patients preferred booklets and pamphlets, while more
      older patients preferred television and radio. The most needed cancer information
      at the time of diagnosis and treatment involved diagnosis, stage, and prognosis
      while after treatment ended it involved self-care techniques. CONCLUSIONS:
      Cervical cancer patients' need of cancer information varied with age and
      treatment phase. These findings should help guide the development of educational
      materials tailored to the needs of individual patients.

PMID- 19172302
TI  - 'Quite an awkward situation to be in': perceptions of patients, carers and health
      and social care professionals of the supportive cancer care in British military
      personnel stationed in Germany.
AB  - GOALS OF WORK: This paper reports findings from a study which identified the
      nature and volume of supportive care received by British military services
      personnel and their dependents who experience cancer and are based in Germany.
      The objectives were to (1) identify any gaps in the provision of supportive care,
      (2) determine the potential for additional supportive care services (local or
      remote), and (3) identify any educational or development issues for DMWS
      personnel. MATERIALS AND METHODS: Interviews and focus groups were conducted with
      people with cancer (n = 7), informal carers (n = 6), British health care
      professionals employed by British Forces in Germany (n = 8), German health care
      professionals (n = 3), senior military personnel (n = 6) and army support
      personnel (n = 5). Analysis of the data was thematic and focused on accounts of
      care related to core issue identified in the UK's National Institute of Health
      and Clinical Excellence (NICE) guidelines (24). MAIN RESULTS: The paper explores
      the difficulties which British military personnel experience in their cancer
      care. The shortfalls in best practice are discussed in the framework of NICE
      guidelines focusing on communication, information, psychosocial care and
      coordination of care/inter-agency working. Significant gaps in the supportive
      care service provision are apparent CONCLUSIONS: The limited assessment and
      discussion of patients' supportive care needs suggests key areas for service
      improvement for providers both within the British Military in Germany, and in the
      services provided by German organisations. These findings highlight issues that
      should be considered by those providing supportive care for marginalised patient
      groups, such as patients and carers from different cultures.

PMID- 19172303
TI  - Effects of nutritional and psychological status of the patients with advanced
      stomach cancer on physical performance status.
AB  - GOALS OF THE WORK: The aim of this study was to assess the associations between
      coping mode, nutritional status, and psychological status and performance status
      of the patients with advanced stomach cancer. MATERIALS AND METHODS: An
      epidemiological survey was conducted among 233 patients with advanced stomach
      cancer in Fujian, China. In-person interviews were performed for the participants
      with respect to information of psychological status prior to chemotherapy,
      nutritional status during chemotherapy, and physical performance status after
      chemotherapy. MAIN RESULTS: Multivariate logistic regression analyses showed that
      the level of hemoglobin (HB), level of daily calorie intake, score of Depression
      Status Inventory (DSI), and score of confrontation subscale of Medical Coping
      Modes Questionnaire had a significant influence on performance status (P < 0.05).
      The relative risks (95% confidence interval) were 2.06 (1.12-3.79) for low level
      of hemoglobin versus normal level of hemoglobin, 1.16 (1.02-1.32) for low level
      of daily calorie intake versus normal level of daily calorie intake, 5.89 (2.00
      17.31) for DSI score > or =40 versus DSI score <40, and 3.17 (1.73-5.78) for low
      score of confrontation versus high score of confrontation, respectively.
      CONCLUSIONS: Depression, low score of "Confrontation", low levels of HB, and low
      level of daily calorie intake may be the risk factors of poor performance status
      of the patients with advanced stomach cancer.

PMID- 19172304
TI  - Modesty and recognition--a qualitative study of the lived experience of recovery
      from anal cancer.
AB  - BACKGROUND: Anal cancer is a rare disease within the cancer spectrum. Long-term
      disabilities are notable and place increased demands on rehabilitation. AIM: The
      objective of this study was to describe the lived experiences of recovery from
      anal cancer, including which and how resources may help survivors of anal cancer
      to resist and to manage potentially complex stressors encountered in the recovery
      from the disease. DESIGN: A qualitative, salutogenetic-oriented, phenomenological
      study was conducted based on audio-taped, semi-structured interviews. METHODS:
      Interviewee selection was carried out through purposeful sampling. Sixteen
      individuals (11 women and five men; average age 52 years), who had completed
      therapy for anal cancer (average 31 months ago), participated in the study.
      Transcripts from the audio-taped interviews were used for qualitative text
      condensation analysis, inspired by Giorgi's phenomenological methodology.
      FINDINGS: The analysis revealed two concepts, modesty and recognition, which
      describe the essence of the lived experience of anal cancer, and which each
      appear to be important resistance resources. While modesty is regarded as an
      enforced and necessary competence developed and mastered by the individual,
      recognition refers to a desired, but often lacking, resource in the individual's
      interaction with health authorities and relatives. DISCUSSION: Anal cancer
      appears to lack attention and deserved recognition from professional and social
      services, which in itself may lead to mistrust and devaluation of the individual
      seeking support. It is recommended that both researchers and rehabilitation
      services incorporate, prioritize, and advise on the disease's specific issues and
      the terms under which the survivor can maintain an active, working and social
      life, as desired.

PMID- 19172305
TI  - Evaluation of intervention to prevent hypomagnesemia in cervical cancer patients
      receiving combination cisplatin and radiation treatment.
AB  - PURPOSE: The purpose of this study was to evaluate the impact of increasing the
      magnesium (Mg(2+)) supplementation in the pre- and posthydration of patients
      receiving cisplatin plus radiation (CisXRT) to prevent chemotherapy-induced
      hypomagnesemia (CIH) events. MATERIALS AND METHODS: The study was conducted on
      newly diagnosed cervical cancer patients receiving CisXRT. The first prospective
      intervention to prevent CIH was to increase the pre- and posthydration Mg(2+)
      from 1 to 2 g. After completion of the first intervention, the analysis
      demonstrated the persistent occurrence of CIH on cycle 3, and later, a second
      intervention was implemented to increase Mg(2+) to 3 g in the pre- and
      posthydration. Patients that failed to complete at least five cycles or received
      cisplatin in combination with another chemotherapy regimen were excluded from the
      study. Baseline group included 70 patients that had received CisXRT prior to any
      changes in magnesium supplementation. RESULTS: There were 62.8% (44/70) and 32.6%
      (22/70) of patients with episodes of CIH in the baseline and first intervention
      groups, respectively (P = 0.007). In the second intervention group, a 49.6%
      decrease in the total number of episodes compared to control group was observed.
      Patients in the second intervention group showed a 100% improvement incidence of
      persistent CIH over the two other cohorts (P = 0.001). CONCLUSIONS: The increase
      of Mg(2+) to 2 g for the initial two cycles and then to 3 g with the third cycle
      of CisXRT therapy prevented episodes of CIH and decreased associated treatment
      delays.

PMID- 19172306
TI  - Bortezomib-related colon mucositis in a multiple myeloma patient.

PMID- 19172308
TI  - Interobserver reliability and intraobserver reproducibility of Powers ratio for
      assessment of atlanto-occipital junction: comparison of plain radiography and
      computer tomography (Kirkham B. Wood; ESJO-D-08-00378R2).

PMID- 19172309
TI  - Management of intramedullary spinal cord abscess: experience with four cases,
      pathophysiology and outcomes.
AB  - Intramedullary spinal cord abscess (ISCA) in children is extremely a rare
      infection of the central nervous system (CNS); and probably a devastating
      neurological condition. Clinical awareness of patients at risk is crucial for
      early diagnosis and intervention; as this entity is one of the treatable
      conditions of paraparesis. Association with congenital neuro-ectodermal
      abnormality in children is frequent. This pathology highlights the importance of
      complete neurological checks of infants as a part of their routine physical
      examination and early management of patients with congenital dermal sinus,
      prophylactic surgical resection of such a congenital anomaly is recommended by
      most authors to prevent serious infections of the CNS. However, once the abscess
      is established; immediate surgical drainage along side adequate antibiotics
      should be instituted. This may guarantee improving neurological outcome. In this
      communication, the authors present their experience with four cases of ISCA in
      children treated successfully with surgical drainage, intravenous antibiotics and
      neuro rehabilitation between 2001 and 2006 and discuss their results. We
      concluded that early diagnosis and treatment is essential; before a devastating
      mechanico-vascular insult of the spinal cord is established from rapid formation
      of the abscess and a swift expansion of the spinal cord within the limited
      intraspinal space.

PMID- 19172310
TI  - Reviewer's comment concerning "The effect of intraoperative skeletal (skull
      femoral) traction in apical vertebral rotation" by St Lewis et al. (MS-no: ESJO-D
      08-00312R1).

PMID- 19172311
TI  - Pulsed radiofrequency effects on the lumbar ganglion of the rat dorsal root: a
      morphological light and transmission electron microscopy study at acute stage.
AB  - Since the dorsal root ganglia represent the first structure of pain modulation,
      they are the target of the newest therapies of neuropathic pain. Between these,
      pulsed radiofrequency (PRF) has been described among the promising non-invasive
      methods. Although the results encourage the clinical use of this procedure, their
      mechanism of action is still unclear. Aim of our study was to analyze acute
      effects of PRF on the rat lumbar ganglion and on nervous fibres running inside
      it. Clinical works describe PRF treatment as a technique without any visible
      neurological deficit. The few disposable histological works are contractictory:
      some describe no signs of cellular damage and some demonstrate visible
      intracellular modifications. A total of 20 male Wistar rats were deeply
      anesthesized. Ten were positioned in a stereotactic system, and exposed to PRF at
      2 Hz for 30 s after exposition of paravertebral muscles and positioning of a
      stimulation needle on left L4 ganglion. The other ten were used as controls.
      After 1 h, the left dorsal root ganglions L3, L4, L5 of the 20 animals were
      explanted, fixed in 2.5% Karnowsky solution and prepared for light and
      transmission electron microscopy. At light microscopy no differences between
      treated and control animals were observed; at transmission electron microscopy,
      instead, it was possible to observe that T gangliar cells contained an abnormal
      abundant smooth reticulum with enlarged cisternae and numerous vacuoles;
      myelinated axons presented pathological features and their myelin coverage was
      not adherent. Instead, unmyelinated axons appeared normal in shape and dimension
      and the Schwann cells surrounding it had intact plasmamembrane. Our results,
      obtained at acute stage, reveal that the PRF procedure should destroy the myelin
      envelope of nervous fibres. Further future studies, at chronic stage, should give
      other information on the prognosis of the myelinic damage.

PMID- 19172313
TI  - Mucocele of the gland of Blandin-Nuhn: histological and clinical findings.
AB  - The authors examined the clinical and histopathological features of 48 cases of
      mucocele of the glands of Blandin-Nuhn. Data of all patients with mucocele
      treated at the Department of Oral and Maxillofacial Surgery totaled 312 cases
      during the 6-year period of study were analyzed. There was no sex predominance,
      and most patients were younger than 20 years. All lesions were located on the
      ventral surface of the tongue, and they were more frequently observed at the tip
      of the tongue whereas few ones occurred more posteriorly. All lesions presented a
      polypoid appearance. Histopathologically, the mucoceles were of the extravasation
      type and trauma might be the most frequent etiological factor. This type of
      mucocele was the second most frequent one and should not be considered rare.

PMID- 19172312
TI  - Theoretical study of cyclohexane hydroxylation by three possible isomers of
      [FeIV(O)(R-TPEN)] 2+: does the pentadentate ligand wrapping around the metal
      center differently lead to the different stability and reactivity?
AB  - Density functional theory calculations have been carried out to elucidate the
      mechanism of cyclohexane hydroxylation by three possible isomers of [Fe(IV)(O)(N
      R-N,N',N'-tris(2-pyridylmethyl)ethane-1,2-diamine)](2+) (R is methyl or benzyl)
      (Klinker et al. in Angew Chem Int Ed 44:3690-3694, 2005). The calculations offer
      a mechanistic view and reveal the following features: (a) all the three isomers
      possess triplet ground states and low-lying quintet excited states, (b) the
      relative stability follows the order isomer A > isomer B > isomer C, in agreement
      with the conclusions of Klinker et al., (c) the theoretical investigations
      provide a rationale to explain the interconversion of the three isomers, (d) the
      reaction pathways of the C-H hydroxylation are initiated by a hydrogen
      abstraction step, and (e) the three isomers react with cyclohexane via two-state
      reactivity patterns on competing triplet and quintet spin-state surfaces. As
      such, in the gas phase, the relative reactivity exhibits the trend isomer B >
      isomer A, while at the highest level, B2//B1 with zero point energy and solvation
      corrections, the relative reactivity follows the order isomer B > isomer A >
      isomer C. Thus, the calculated reaction pathway shows that pyridine rings
      perpendicular to the Fe-O axis result in more reactive species, and a pyridine
      ring coordinated trans to the oxygen atom leads to the least reactive isomer.

PMID- 19172314
TI  - Dimensional changes of periodontal soft tissues after intrasulcular incision.
AB  - In maxillofacial surgery, intrasulcular incisions are often used. This
      prospective case series was established to evaluate the detrimental effects of
      intrasulcular incisions on periodontal structures. In 35 patients, measurements
      of probing depth and crown length before and 10 months postoperatively were
      performed to calculate changes of attachment level and gingival recession. In a
      subgroup, surgically treated sites were compared with untreated control sites. A
      nonparametric test was applied for longitudinal and split-mouth comparisons.
      Overall, intrasulcular incisions did not induce significant attachment loss. The
      frequency of sites losing > or = 2 mm of attachment was 5.0%, 2.6%, and 4.7% at
      mesial, buccal, and distal sites, respectively. Intrasulcular incisions caused
      only a slight increase in gingival recession by 0.4 +/- 0.5, 0.2 +/- 0.3, and 0.3
      +/- 0.4 mm at mesial, buccal, and distal sites, respectively. Within the
      limitations of the study design, it can be concluded that intrasulcular incisions
      without additional vertical incisions do not impose a serious risk for attachment
      loss and/or gingival recession.

PMID- 19172315
TI  - DFT and electrochemical studies on nortriptyline oxidation sites.
AB  - A study on the possible sites of oxidation and epoxidation of nortriptyline was
      performed using electrochemical and quantum chemical methods; these sites are
      involved in the biological responses (for example, hepatotoxicity) of
      nortriptyline and other similar antidepressants. Quantum chemical studies and
      electrochemical experiments demonstrated that the oxidation and epoxidation sites
      are located on the apolar region of nortriptyline, which will useful for
      understanding the molecule's activity. Also, for the determination of the
      compound in biological fluids or in pharmaceutical formulations, we propose a
      useful analytical methodology using a graphite-polyurethane composite electrode,
      which exhibited the best performance when compared with boron-doped diamond or
      glassy carbon surfaces.

PMID- 19172316
TI  - Theoretical study of 1-(4-hexylcyclohexyl)-4-isothiocyanatobenzene: molecular
      properties and spectral characteristics.
AB  - The mesogenic species 4-(4-hexylcyclohexyl) isothiocyanatobenzene (6CHBT) was
      studied with density functional theory and molecular mechanics in order to
      investigate the molecular properties, interactions between dimers and to
      interpret the IR spectrum. Two types of calculations were performed for model
      systems containing single and double molecules of 6CHBT. Calculations (involving
      conformation analysis) for isolated species indicated that the trans isomer, in
      the equatorial-equatorial conformation, is the most energetically stable. The
      6CHBT molecule is polar, with a rather high (4.43 D) dipole moment with
      negatively charged isothiocyanato (NCS) ligand. The dimer-dimer interaction
      energies show that the head-to-head configuration (where van der Waals attraction
      forces play the major role) is the most energetically stable. Vibrational
      analysis provided detailed assignment of the experimental infra-red (IR)
      spectrum.

PMID- 19172317
TI  - The effects of light-induced reduction of the photosystem II reaction center.
AB  - Accumulation of reduced pheophytin a (Pheo-D1) in photosystem II reaction center
      (PSII RC) under illumination at low redox potential is accompanied by changes in
      absorbance and circular dichroism spectra. The temperature dependences of these
      spectral changes have the potential to distinguish between changes caused by the
      excitonic interaction and temperature-dependent processes. We observed a
      conformational change in the PSII RC protein part and changes in the spatial
      positions of the PSII RC pigments of the active D1 branch upon reduction of Pheo
      D1 only in the case of high temperature (298 K) dynamics. The resulting
      absorption difference spectra of PSII RC models equilibrated at temperatures of
      77 K and 298 K were highly consistent with our previous experiments in which
      light-induced bleaching of the PSII RC absorbance spectrum was observable only at
      298 K. These results support our previous hypothesis that Pheo-D1 does not
      interact excitonically with the other chlorins of the PSII RC, since the reduced
      form of Pheo-D1 causes absorption spectra bleaching only due to temperature
      dependent processes.

PMID- 19172318
TI  - Molecular modeling and dynamics studies of purine nucleoside phosphorylase from
      Bacteroides fragilis.
AB  - Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of
      N-ribosidic bonds of purine nucleosides and deoxynucleosides, except adenosine,
      to generate ribose 1-phosphate and the purine base. This work describes for the
      first time a structural model of PNP from Bacteroides fragilis (Bf). We modeled
      the complexes of BfPNP with six different ligands in order to determine the
      structural basis for specificity of these ligands against BfPNP. Comparative
      analysis of the model of BfPNP and the structure of HsPNP allowed identification
      of structural features responsible for differences in the computationally
      determined ligand affinities. The molecular dynamics (MD) simulation was assessed
      to evaluate the overall stability of the BfPNP model. The superposition of the
      final onto the initial minimized structure shows that there are no major
      conformational changes from the initial model, which is consistent with the
      relatively low root mean square deviation (RMSD). The results indicate that the
      structure of the model was stable during MD, and does not exhibit loosely
      structured loop regions or domain terminals.

PMID- 19172320
TI  - TCNE-aniline charge transfer complex: ab initio and TDDFT investigations in gas
      phase.
AB  - The geometric and electronic structure of tetracyanoethylene (TCNE)-aniline
      (donor-acceptor type) complex has been investigated in gas phase using ab initio
      and time dependent density functional theory calculations. Both the above
      calculations predict a composed structure for the complex, in which the
      interacting site is a C[triple bond]N and C=C bond center in the TCNE and, -NH(2)
      and pi-electrons of aniline. The N atom of aniline is oriented toward the TCNE
      molecule. The charge transfer transition energy, estimated by calculating the
      ground-to-excited state transition electric dipole moments of the complex, agree
      well with the reported experimental value in chloroform medium.

PMID- 19172319
TI  - A computational modeling and molecular dynamics study of the Michaelis complex of
      human protein Z-dependent protease inhibitor (ZPI) and factor Xa (FXa).
AB  - Protein Z-dependent protease inhibitor (ZPI) and antithrombin III (AT3) are
      members of the serpin superfamily of protease inhibitors that inhibit factor Xa
      (FXa) and other proteases in the coagulation pathway. While experimental
      structural information is available for the interaction of AT3 with FXa, at
      present there is no structural data regarding the interaction of ZPI with FXa,
      and the precise role of this interaction in the blood coagulation pathway is
      poorly understood. In an effort to gain a structural understanding of this
      system, we have built a solvent equilibrated three-dimensional structural model
      of the Michaelis complex of human ZPI/FXa using homology modeling, protein
      protein docking and molecular dynamics simulation methods. Preliminary analysis
      of interactions at the complex interface from our simulations suggests that the
      interactions of the reactive center loop (RCL) and the exosite surface of ZPI
      with FXa are similar to those observed from X-ray crystal structure-based
      simulations of AT3/FXa. However, detailed comparison of our modeled structure of
      ZPI/FXa with that of AT3/FXa points to differences in interaction specificity at
      the reactive center and in the stability of the inhibitory complex, due to the
      presence of a tyrosine residue at the P1 position in ZPI, instead of the P1
      arginine residue in AT3. The modeled structure also shows specific structural
      differences between AT3 and ZPI in the heparin-binding and flexible N-terminal
      tail regions. Our structural model of ZPI/FXa is also compatible with available
      experimental information regarding the importance for the inhibitory action of
      certain basic residues in FXa.

PMID- 19172321
TI  - A LRRK2 G2019S mutation carrier from Turkey shares the Japanese haplotype.
AB  - The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is recognized as the
      most common cause of familial autosomal dominant and also sporadic forms of
      Parkinson disease (PD). A common founder has been described for most Europeans
      and all North Africans and Jews; besides, two distinct G2019S LRRK2 haplotypes
      were found in a small proportion of European families and in Japanese PD
      patients. This study revealed a Turkish patient heterozygous for the G2019S
      mutation sharing the Japanese haplotype. To the best of our knowledge, it is the
      first time that the G2019S-associated Japanese haplotype has been reported in a
      different population.

PMID- 19172322
TI  - Tumefactive demyelinating lesions: nine cases and a review of the literature.
AB  - Tumefactive demyelinating lesions (TDLs) are misdiagnosed frequently. To
      investigate the characteristics of TDLs, clinical and radiological data from nine
      cases with TDLs were analyzed after admission. All cases underwent surgery and
      pathological examination; some received postoperative steroid therapy. Onsets
      were mostly within 3 weeks and main presentation included intracranial
      hypertension, extremity weakness, epilepsy, and visual disturbance. Symptoms in
      children were acute and severe, frequently including headache, vomiting, and
      visual disturbance. Most intracephalic lesions were in cerebral hemispheres. All
      intraspinal lesions were in cervical segments. Radiological features included
      mass effect, perifocal edema and enhancement (of which open-ring enhancement was
      diagnostic), and decreased relative cerebral blood volume. Intraoperative frozen
      section did not confirm the diagnosis, while postoperative paraffin section did
      confirm it (by evidence of macrophage infiltration). The patients responded well
      to steroid therapy and no relapse was found during following up. Thus, intensive
      analysis of both clinical and radiological data may provide some clues for
      diagnosis. For suspected cases, it is advisable to take steroid therapy or
      undergo advanced radiological examinations, such as serial magnetic resonance
      spectroscopy. However, in difficult cases, pathological evidence is beneficial to
      a final diagnosis.

PMID- 19172323
TI  - Magnetic resonance spin-labeling perfusion imaging of synovitis in inflammatory
      arthritis at 3.0 T.
AB  - OBJECTIVE: The aim of this study was to test the feasibility of arterial spin
      labeling (ASL) perfusion imaging of synovitis in inflammatory joint diseases on a
      clinical 3.0 T whole-body scanner. MATERIALS AND METHODS: Fifteen patients
      (geometric mean 47 years, range 8-69 years) with different types of inflammatory
      arthritis of the finger or wrist joints participated in the study. In addition to
      conventional spin-echo and dynamic contrast-enhanced FLASH3D sequences, a novel
      spin-labeling technique (FAIR-TrueFISP) for quantitative assessment of tissue
      perfusion was applied. Perfusion maps were calculated pixel-wise by means of the
      extended Bloch equations. RESULTS: Perfusion maps showed good image quality with
      clear visualization of hyperaemia in synovitis. The computed perfusion maps
      corresponded best to subtraction images of the dynamic series from 30 to 60 s
      after contrast-medium injection. The quantitative perfusion values of synovitis
      showed a good correlation with the disease activity. Perfusion values for
      inflamed synovium in phase of high activity were up to 230 ml/100 g tissue/min.
      CONCLUSION: The proposed modality allows for the assessment of disease activity
      in arthritis without the application of contrast-medium offering a new tool for
      therapy monitoring. As the technique provides quantitative information on
      hyperaemia, it potentially offers new insights in the pathophysiology of
      arthritic diseases.

PMID- 19172324
TI  - Shapes and coiling of mixed phospholipid vesicles.
AB  - We have studied some physical properties of mixed phosphatidylcholine (SOPC)
      phosphatidylserine (SOPS) vesicles. In a previous work (Paredes et al. in J Biol
      Phys 32:177-181, 2006) it was shown that the shape of the vesicles depends on the
      SOPC:SOPS composition, and that coiled cylindrical vesicles exist in samples with
      low SOPS contents. In this work, we further studied the same system of mixed
      vesicles. Differential scanning calorimetry (DSC) experiments displayed peaks
      characteristic of lipid mixing in the liquid state, ruling out a possible phase
      transition as an explanation of vesicle coiling. In addition, small-angle X-ray
      scattering (SAXS) experiments allowed us to estimate the periodicity distance
      inside the vesicles. This distance is d approximately equal 60 A, as revealed by
      the Bragg peaks observed in the experiments. Finally, the coiling transition of a
      cylindrical vesicle was observed under solvent flow. This observation indicates
      that the vesicle coiling reported previously for this system (Paredes et al. in J
      Biol Phys 32:177-181, 2006) does not depend on the SOPC:SOPS composition alone,
      but also on mechanical perturbations during the preparation steps.

PMID- 19172325
TI  - Psychological impact of disasters on children: review of assessment and
      interventions.
AB  - BACKGROUND: There is a wide range of mental and behavioral sequel in children
      following disasters, which can last long. This review discusses the nature and
      extent of the psychiatric problems, their management options and process to
      organize the psychological interventions for affected children. DATA SOURCES:
      Literatures were searched through PubMed with the words "children, disaster,
      psychiatry, and mental health" and relevant cross references were included in the
      review. RESULTS: Proportions of children having posttraumatic symptoms or
      syndromal diagnoses vary in different studies depending on various factors like
      nature and severity of disaster, diagnostic criteria used, cultural issues
      regarding meaning of trauma, support available, etc. Common psychiatric
      manifestations among children include acute stress reactions, adjustment
      disorder, depression, panic disorder, post-traumatic stress disorder, anxiety
      disorders specific to childhood and psychotic disorders. Comorbidities and sub
      clinical syndromes are also common. Most of the post-disaster mental health
      interventions can be provided in the community by the local disaster workers.
      Supportive counselling, cognitive behavior therapy, brief trauma/grief-focused
      psychotherapy, and play therapy are the commonly utilized methods of
      psychological intervention, which can be given in groups. Information about the
      efficacy of medications is still emerging, while many are being used and found
      useful. CONCLUSIONS: Following disaster, systematic screening for psychological
      problems in children is suggested. An integrated approach using psycho-socio
      educational and clinical interventions is expected to be effective.

PMID- 19172326
TI  - Psychopathology and psychological adjustment in children and adolescents with
      epilepsy.
AB  - BACKGROUND: Epilepsy is the most common chronic neurological illness in childhood
      and adolescence, and this condition may increase the risk of psychopathology at
      these ages. DATA SOURCES: A literature review, including MEDLINE and PsychLIT
      database, was made covering the period of 1966-2007. Research studies were
      included if they were concerned with children suffering from epilepsy and
      measures of psychopathology. RESULTS: Studies found a more elevated rate of
      psychological and psychiatric disorders, both behavioral and emotional, in these
      samples compared to general population or children with other chronic conditions.
      The problems presented in children and adolescents with epilepsy are quite
      similar to those in general population with a slight increase of hyperkinetic and
      attention problems likely related to both direct brain damage and anticonvulsant
      treatment. There is no evidence of psychotic disorders and/or specific
      personality traits associated with epilepsy at these ages. CONCLUSIONS: Family
      factors, specially those related to psychopathology in other family members and
      parent-child relationships, appear to have stronger influence on children
      psychopathology than illness factors themselves. Some guidelines are provided in
      order to improve future research.

PMID- 19172327
TI  - Prenatal diagnosis and treatment planning of congenital heart defects
      possibilities and limits.
AB  - BACKGROUND: Newborns with hypoplastic left heart syndrome (HLHS) or right heart
      syndrome or other malformations with a single ventricle physiology and associated
      hypoplasia of the great arteries continue to be a challenge in terms of survival.
      The vast majority of these forms of congenital heart defects relate to abnormal
      morphogenesis during early intrauterine development and can be diagnosed
      accurately by fetal echocardiography. Early knowledge of these conditions not
      only permits a better understanding of the progression of these malformations but
      encourages some researchers to explore new minimally invasive therapeutic options
      with a view to early pre- and postnatal cardiac palliation. DATA SOURCES: PubMed
      database was searched with terms of "congenital heart defects", "fetal
      echocardiography" and "neonatal cardiac surgery". RESULTS: At present, early
      prenatal detection has been applied for monitoring pregnancy to avoid
      intrauterine cardiac decompensation. In principle, the majority of congenital
      heart defects can be diagnosed by prenatal echocardiography and the detection
      rate is 85%-95% at tertiary perinatal centers. The majority, particularly of
      complex congenital lesions, show a steadily progressive course including
      subsequent secondary phenomena such as arrhythmias or myocardial insufficiency.
      So prenatal treatment of an abnormal fetus is an area of perinatal medicine that
      is undergoing a very dynamic development. Early postnatal treatment is
      established for some time, and prenatal intervention or palliation is at its best
      experimental stage in individual cases. CONCLUSION: The upcoming expansion of
      fetal cardiac intervention to ameliorate critically progressive fetal lesions
      intensifies the need to address issues about the adequacy of technological
      assessment and patient selection as well as the morbidity of those who undergo
      these procedures.

PMID- 19172328
TI  - Metabolic syndrome in fifth grade children with acanthosis nigricans: results
      from the CARDIAC project.
AB  - BACKGROUND: A number of cardiovascular disease (CVD) risk factors have been
      linked to obesity and associated negative health outcomes in children. However,
      no consistent definition of metabolic syndrome exists for children. In addition,
      research is needed to systematically examine the prevalence of metabolic syndrome
      in high-risk children, including those with insulin resistance. This study
      explores several definitions of metabolic syndrome and determines the prevalence
      of metabolic syndrome in a large sample of children with acanthosis nigricans
      (AN). METHODS: The study used results from a large-scale screening of fifth-grade
      students in West Virginia to explore the prevalence of metabolic syndrome among
      676 male and female participants who had mild to severe AN. RESULTS: In this high
      risk sample of students who had AN, 49% met the criteria, i.e., three risk
      factors including insulin resistance, high body-mass index, and elevated blood
      pressure or dyslipidemia, when tested for metabolic syndrome. Children with AN
      who were classified as obese or morbidly obese were at significantly increased
      odds of having metabolic syndrome. CONCLUSIONS: Results are discussed in terms of
      systematically defining metabolic syndrome for high-risk children, as well as
      public health and clinical interventions targeting children who are overweight or
      obese. The presence of AN and morbid obesity might be easily observed markers for
      metabolic syndrome.

PMID- 19172329
TI  - Melamine-contaminated milk products induced urinary tract calculi in children.
AB  - BACKGROUND: Melamine is an industrial chemical used primarily as plastics
      stabilizer and fire retardant. On September 11, 2008, melamine-contaminated milk
      products were reported to be responsible for urinary tract calculi in infants and
      children in China. This study aimed to investigate the prevalence, lesions, risk
      factors, clinical features, and management of children fed with the melamine
      contaminated milk products. METHODS: A total of 15 577 infants and children fed
      with the milk products were screened at our hospital. Ultrasonography was
      performed in all the infants and children. For those found with urinary tract
      calculion ultrasonography, urnalysis was done. Among them, 846 with detailed data
      screened from September 17 to 25 were enrolled for further analysis in this
      study. They were divided into calculus group (326 children) and non-calculus
      group (520 children) according to the results of ultrasonography. They included
      429 boys and 417 girls, aged from 1 month to 5 years (median, 18 months). Their
      clinical and laboratory data, ultrasonograms, and treatment results were
      analyzed. RESULTS: Of the 15 577 children screened, 562 (3.61%) had urinary tract
      calculi. The rate was closely related to the melamine concentration in patients
      fed with formula. In 846 children with detailed data enrolled in this analysis,
      weight and head circumference Z scores in the calculus group were lower than
      those in the non-calculus group (P=0.048, P=0.046). Long duration of formula
      feeding, high melamine contained formula, and minimal water intake were the risk
      factors for calculi (P<0.05, respectively). Of 326 children with calculi, 281 had
      small calculiless than 0.5 cm in diameter, 227 had multiple calculi, and 34 had
      urinary tract distention. Moreover, diffuse renal lesions, renal failure and
      ascites were noted in 4, 3 and 2 patients, respectively. After 1-month treatment
      with sodium bicarbonate and Chinese traditional medicine, calculi disappeared in
      49 of 54 outpatients. In 41 inpatients, 5 had calculi removed operatively and 36
      had calculi minimized. CONCLUSIONS: Melamine-contaminated milk products induced
      urinary tract calculi, which have a good response to conservative therapy. Long
      term follow-up of infants and children fed with melamine-contaminated milk
      products is required, and food safety should be supervised increasingly for the
      health of children.

PMID- 19172330
TI  - Breast-feeding history and overweight in 11 to 13-year-old children in Iran.
AB  - BACKGROUND: The relationship between breast-feeding history and risk of
      overweight in pre-adolescent children was investigated. METHODS: Children's
      breast-feeding history and demographics were obtained in interviewer-administered
      questionnaires of a multistage cluster sample survey of 800 parents of children
      aged 11-13 years living in Yazd, Iran. Height and weight were measured in the
      children. Overweight was defined as body mass index >/=90th age- and sex-specific
      percentile of the 2000 Centers for Disease Control reference values. RESULTS: One
      hundred and four (13.0%) of 800 children were overweight. A total of 783 (97.9%)
      of the children had been breast fed. There was a markedly lower overweight
      prevalence among breast-fed than non breast-fed children. Controlling for age and
      sex, children breast fed for at least 24 months were substantially less likely to
      be overweight than children breast fed for less than 12 months (OR 0.56, 95% CI
      0.31-0.9). A longer overall duration and duration of exclusive breast-feeding
      were associated significantly with the decreasing prevalence of overweight.
      CONCLUSION: This sample of Iranian children shows high rates of overweight at
      young ages but also high rates of breast-feeding. The duration of breast-feeding
      is inversely related with the prevalence of overweight in pre-adolescent
      children.

PMID- 19172331
TI  - Bilirubin levels predict renal cortical changes in jaundiced neonates with
      urinary tract infection.
AB  - BACKGROUND: This study was undertaken to determine the incidence of urinary tract
      infection (UTI) and the frequency of anatomical abnormalities in newborns with
      unexplained jaundice and to find out if there is any correlation between
      bilirubin level and renal damage. METHODS: We studied 462 full-term neonates for
      UTI. They were aged 3-25 days, with either high (>10 mg/dL) or prolonged (>10
      days) hyperbilirubinemia, with or without manifestations such as fever, vomiting,
      diarrhea, poor feeding, lethargy, and irritability. Neonates positive for UTI
      were further investigated with ultrasound, cystourethrography, and acute phase
      renal scintigraphy with technetium-99m dimercaptosuccinate acid (DMSA). RESULTS:
      Thirty neonates (6.5%) were found to have UTI. Twenty-eight of them had indirect
      hyperbilirubinemia and two had direct hyperbilirubinemia, with total bilirubin
      levels of 11.8-20.1 mg/dL. None of the neonates was found to have jaundice
      because of other reasons such as infection. Vesicoureteral reflux was found in 5
      neonates and one of them was combined with hydronephrosis. Renal scintigraphy
      with technetium-99m DMSA showed renal cortex changes in 14 (46.7%) of the 30
      neonates with UTI. These 14 neonates also had increased levels of bilirubin in
      comparison to those with normal findings of DMSA. CONCLUSIONS: The incidence of
      UTI in uncomplicated neonatal jaundice is relatively high. Anatomical
      abnormalities of the urinary tract are not rare in infected children. Increased
      bilirubin levels are related to pathological findings in renal scintigraphy.

PMID- 19172332
TI  - A practical screening model for hearing loss in Iranian school-aged children.
AB  - BACKGROUND: Hearing loss is a common and considerable disability that harms
      educational performance of school children in developing countries like Iran.
      Lack of a simple and practical screening protocol often deters routine and
      systematic hearing screening at school entry. METHODS: This study was to
      establish a practical screening model for hearing loss in school-aged children
      based on a community-based, retrospective casecontrol study in Ilam, the capital
      of Ilam province in Iran. Results from the audiologic and non-audiologic
      examination of 785 children in primary schools were selected and examined. The
      non-audiologic evaluation consisted of medical history, general physical
      examination, while the audiologic assessment consisted of otoscopy, audiometry
      and tympanometry. RESULTS: Univariate analysis of non-audiologic variables showed
      an association between hearing loss and male gender (P<0.05) and the grade of
      study (P<0.05). The frequency of impaired hearing in the first grade of primary
      schools was significantly higher than the children in the second grade (P<0.05).
      In audiologic factors related to impaired hearing, otitis media with effusion
      (OME) was diagnosed significantly (P<0.05). CONCLUSION: Routine screening based
      on the identification of OME will facilitate the detection of a major amount of
      hearing impaired school-aged children.

PMID- 19172333
TI  - Why we are still doing so many exchange blood transfusion for neonatal jaundice
      in Nigeria.
AB  - BACKGROUND: Since exchange blood transfusion (EBT) is associated with serious
      complications, phototherapy has been made more powerful to reduce the need for
      EBT in the developed world. This study was undertaken to determine the
      indications for EBT in neonatal jaundice (NNJ) at our unit and what proportion of
      EBTs was possibly avoidable. METHODS: All the babies who had EBT for
      hyperbilirubinemia over a three-year period were included. Age, sex, weight,
      place of delivery, blood group of baby and mother, other investigations,
      management, and the outcome of the babies were recorded. RESULTS: Of the 1686
      babies admitted to the neonatal unit, 90 (5.3%) had EBT. Fourteen (15.6%) were
      inborn while 76 (84.4%) were out-born babies. Fifty-six (62.2%) babies were
      admitted primarily for NNJ while 34 (37.8%) developed NNJ during admission.
      Thirty-six (40.0%) of the babies had phototherapy for more than 24 hours prior to
      EBT either because they were of very low birthweight or NNJ was detected very
      early and therapy was so commenced. Sixty-eight (75.6%) babies had single EBT
      while the remaining 22 (24.4%) had two sessions of EBT. Factors associated with
      severe NNJ in babies requiring EBT included low birthweight (<2500 g, 44.4%), ABO
      incompatibility (30.0%), glucose-6-phosphate dehydrogenase deficiency (34.4%) and
      septicemia (26.1%). Twenty-seven (30.0%) of the neonates developed features of
      kernicterus: 26 before admission while 1 during admission; all except one were
      delivered outside the hospital. CONCLUSIONS: The EBT rate in our center was high.
      With more effective phototherapy, EBT could be avoided in most of the babies who
      initially had phototherapy for more than 24 hours before EBT and repeated EBT
      sessions. Health education of the population at risk, especially pregnant women,
      and early referral at the primary health care level will reduce the burden of
      severe NNJ.

PMID- 19172334
TI  - Diagnosis and management of esophageal achalasia in children: analysis of 13
      cases.
AB  - BACKGROUND: Esophageal achalasia is a rare disease and there have been very few
      reports about it, especially in children. We reviewed our experience in dealing
      with esophageal achalasia in 13 children. METHODS: Thirteen children (6 boys and
      7 girls), who had been diagnosed with achalasia over a 12-year period between May
      1993 and October 2005, were analysed with regard to clinical manifestations,
      esophageal manometry, endoscopic findings, and treatment. Their age ranged from 3
      years to 14 years and 5 months (average 10.3 years) at the time of diagnosis.
      RESULTS: In the 13 children, 3 had a family history of esophageal achalasia, 2 of
      them were sisters. All the 3 children suffered from achalasia/alacrimia/ACTH
      deficiency. Dysphagia was the most common symptom in the affected children.
      Vomiting/regurgitation, retrosternal pain, retarded growth, and respiratory
      symptoms were also observed in some patients. Heller's esophagocardiomyotomy was
      performed in 9 (69.23%) children, among whom 3 had an antireflux operation at the
      same time. In the remaining 4 children, 3 received a pneumatic dilatation and 1
      received regular administration of nifedipine. Twelve patients were followed up:
      8 patients by surgery were cured and have been in perfect condition until now, 3
      patients recovered fairly, and 1 patient showed improvement. CONCLUSIONS:
      Esophageal manometry combined with X-ray examination proves to be an effective
      diagnostic method for achalasia. It is also effective in evaluating the result of
      treatment. Heller's esophagocardiomyotomy is a treatment of choice for children
      with achalasia because of its safety and long-term effective results after
      surgery.

PMID- 19172335
TI  - Serum total and free carnitine levels in children with asthma.
AB  - BACKGROUND: Serum carnitine is decreased in recurrent pulmonary infections. We
      aimed to evaluate serum carnitine levels in asthmatic children. METHODS: Study
      group consisted of children with stable asthma and those with acute asthma
      attacks, while control group included healthy children. Attack severity was
      determined by the pulmonary score system. Total and free carnitine levels were
      studied in one blood sample from the control group and stable asthmatics and in
      two samples from children with acute asthma exacerbation during and after the
      attack. RESULTS: All the 40 patients in the study group had moderate asthma
      including 30 with acute attack (13 mild and 17 moderate) and 10 with stable
      asthma. Carnitine levels were significantly lower in acute attack asthmatics than
      in the stable asthmatics and controls, while there was no significant difference
      between the latter two groups. Carnitine levels were not different between
      asthmatics with mild and moderate attack, and were similar during and after an
      acute attack. CONCLUSIONS: Serum carnitine levels decrease in children with
      moderate asthma during exacerbation of asthma and shortly thereafter. Further
      studies are needed to evaluate the effect of carnitine treatment on serum
      carnitine level.

PMID- 19172336
TI  - Neuroimages of persistent falcine sinus in children.

PMID- 19172338
TI  - Congenital pulmonary lymphangiectasis.
AB  - BACKGROUND: Congenital pulmonary lymphangiectasis (CPL) characterized by
      dilatation of pulmonary lymphatic vessels occurs as a congenital anomaly. With
      poor prognosis, neonatal presentation of bilateral CPL is associated with the
      severe compromise of pulmonary gas exchange and high mortality. METHODS: A male
      infant born at 39 weeks of gestation was found to have CPL. Cyanosis and cardiac
      arrest occurred a few minutes after birth, and the symptoms remained after
      artificial ventilation. The infant died of hypoxemic cardiac failure 45 minutes
      after birth. Autopsy showed neither pleural effusion nor valvular abnormalities.
      RESULTS: Microscopically dilated vessels with lymphatics were seen in the lung of
      the infant. Atelectasis, CPL, inhalation of amniotic fluid, partial hydropic
      degeneration of hepatic cells, and scrotal edema were diagnosed. CONCLUSION: With
      regard to treatment and prognosis, CPL must be distinguished from interstitial
      emphysema and other diseases.

PMID- 19172337
TI  - Is there a correlation between venlafaxine therapy during pregnancy and a higher
      incidence of necrotizing enterocolitis?
AB  - BACKGROUND: Novel antidepressant drugs are increasingly used by women of child
      bearing age. However, potentially harmful effects on fetus and newborn remain
      unknown. METHODS: Case report and literature review. RESULTS: We present preterm
      twins whose mother was treated with venlafaxine, a nonselective serotonin
      reuptake inhibitor, throughout pregnancy until delivery. The twins developed
      neonatal necrotizing enterocolitis. CONCLUSION: The question whether there might
      be a correlation between maternal serotonin reuptake inhibitor therapy and
      neonatal necrotizing enterocolitis is discussed.

PMID- 19172339
TI  - Intracranial solitary juvenile xanthogranuloma in an infant.
AB  - BACKGROUND: Juvenile xanthogranuloma (JXG) is a disorder of histiocyte
      proliferation. Most cases present with a solitary cutaneous lesion. JXG with
      systemic involvement is rare with significant morbidity. Intracranial solitary
      JXG may be misdiagnosed before operation. METHODS: A 5-month-old boy showed an
      elevated anterior fontanel but no other abnormalities on admission. Brain MRI
      showed a large mass in the right parietal region. RESULTS: The tumor was removed
      with the encroached meninges. A JXG in the right parietal region was diagnosed
      pathologically. CONCLUSION: Total excision of the tumor may be curative with a
      prerequisite of ensuring normal vital signs and nervous function.

PMID- 19172340
TI  - A tension pneumocephalus caused by severe traumatic brain injury.

PMID- 19172342
TI  - Evaluating obesity in fibromyalgia: neuroendocrine biomarkers, symptoms, and
      functions.
AB  - The aim of this study was to investigate the associations between obesity and
      fibromyalgia syndrome (FMS). This study was conducted at the University of Utah
      Pain Management and Research Center, Salt Lake City, Utah. Thirty-eight FMS
      patients were included in this study. Neuroendocrine indices (catecholamines,
      cortisol, C-reactive protein [CRP], and interleukin-6), symptom measures
      (Fibromyalgia Impact Questionnaire), sleep indices (Actigraph), and physical
      functioning (treadmill testing) were measured. Body mass index (BMI) provided the
      primary indicator of obesity. Approximately 50% of the patients were obese and an
      additional 21% were overweight. Strong positive associations were found between
      BMI and levels of IL-6 (r=0.52) and epinephrine (r=0.54), and somewhat weaker
      associations with cortisol (r=0.32) and CRP (r=0.37). BMI was also related to
      maximal heart rate (r=0.33) and inversely related to distance walked (r= -0.41).
      BMI was associated with disturbed sleep: total sleep time (r= -0.56) and sleep
      efficiency (r= -0.44). No associations between self-reported symptoms and BMI
      were found. This study provides preliminary evidence suggesting that obesity
      plays a role in FMS-related dysfunction.

PMID- 19172341
TI  - Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover
      markers in postmenopausal women.
AB  - Current treatments for postmenopausal osteoporosis suffer from side effects. Safe
      and natural milk proteins, ribonuclease, and lactoferrin promote formation of new
      capillaries and bone formation. A ribonuclease-enriched lactoferrin supplement
      studied here, demonstrates significant reduction in resorption and increase in
      formation, towards restoring the balance of bone turnover within 6 months.
      INTRODUCTION: Osteoporosis, a major health issue among postmenopausal women,
      causes increased bone resorption and reduced bone formation. A reduction in
      angiogenesis could also contribute to this imbalance. Current treatments such as
      hormone replacement therapy and bisphosphonates have drawbacks of severe side
      effects. Milk ribonuclease (RNase) is known to promote angiogenesis and
      lactoferrin (LF) to stimulate bone formation by osteoblasts. We examine the
      effect of ribonuclease-enriched lactoferrin supplement on the bone health of
      postmenopausal women. METHODS: A total of 38 healthy, postmenopausal women, aged
      45 to 60 years were randomized into placebo or RNAse-enriched-LF (R-ELF)
      supplement groups. The bone health status was monitored by assessing bone
      resorption markers, serum N-telopeptides (NTx), and urine deoxypyridinoline (Dpd)
      crosslinks and serum bone formation markers, bone-specific alkaline phosphatase
      (BAP), and osteocalcin (OC). RESULTS: R-ELF supplementation demonstrated a
      decrease in urine Dpd levels by 14% (19% increase for placebo) and serum NTx
      maintained at 24% of the baseline (41% for placebo), while serum BAP and OC
      levels showed a 45% and 16% elevation (25% and 5% for placebo). CONCLUSIONS: R
      ELF supplementation demonstrated a statistically significant reduction in bone
      resorption and increase in osteoblastic bone formation, to restore the balance of
      bone turnover within a short period.

PMID- 19172343
TI  - Role of glycemic elements of Cynodon dactylon and Musa paradisiaca in diabetes
      management.
AB  - The study defined the scientific evaluation of glycemic elements of extracts of
      Cynodon dactylon and Musa paradisiaca. A dose of 500 mg/kg body weight (bw) of C.
      dactylon produced maximum falls of 23.2% and 22.8% in blood glucose levels of
      normoglycemic rats during studies of fasting blood glucose and glucose tolerance,
      respectively, whereas the same dose of M. paradisiaca produced a rise of 34.9%
      and 18.4%. In diabetic rats during glucose tolerance tests, a fall of 27.8% and a
      rise of 17.5% were observed with the same dose of C. dactylon and M. paradisiaca,
      respectively. Laser-induced breakdown spectroscopy used for detection of glycemic
      elements present in both the extracts indicated that C. dactylon was rich in
      magnesium (Mg), whereas M. paradisiaca was rich in potassium (K) and sodium (Na),
      comparatively, suggesting thereby the defined roles of these elements in diabetes
      management.

PMID- 19172344
TI  - Effect of low-level laser irradiation and epidermal growth factor on adult human
      adipose-derived stem cells.
AB  - The study investigated the effects of low-level laser radiation and epidermal
      growth factor (EGF) on adult adipose-derived stem cells (ADSCs) isolated from
      human adipose tissue. Isolated cells were cultured to semi-confluence, and the
      monolayers of ADSCs were exposed to low-level laser at 5 J/cm(2) using 636 nm
      diode laser. Cell viability and proliferation were monitored using adenosine
      triphosphate (ATP) luminescence and optical density at 0 h, 24 h and 48 h after
      irradiation. Application of low-level laser irradiation at 5 J/cm(2) on human
      ADSCs cultured with EGF increased the viability and proliferation of these cells.
      The results indicate that low-level laser irradiation in combination with EGF
      enhances the proliferation and maintenance of ADSCs in vitro.

PMID- 19172345
TI  - Value of laparoscopic appendectomy in the elderly patient.
AB  - BACKGROUND: Acute appendicitis (AA) in elderly patients (60 years of age and
      older) is a challenging problem associated with significant morbidity and
      mortality when perforation is present. We hypothesized that laparoscopic
      appendectomy (LA) would enable an earlier correct diagnosis and have advantages
      in elderly patients. METHODS: We performed a retrospective review of patients who
      underwent laparoscopic appendectomy for suspected AA. Data of elderly patients
      were compared to data of younger patients (18 to <60 years of age). RESULTS:
      Fifty-four LA were performed in elderly patients and 423 in younger patients.
      Patients over the age of 60 years had more co-morbidities and required more
      frequent use of anticoagulants. Preoperative imaging (ultrasound or computerized
      tomography) was significantly more frequent in elderly patients (36% versus 15%),
      and was associated with a higher rate of confirmation of acute appendicitis (78%
      versus 55%), which allowed a decrease in the rate of negative surgical
      explorations to 4.1% in elderly patients compared to 10.2% in younger patients.
      Complicated appendicitis and conversions were more frequent in the elderly
      patients. This resulted in prolonged operative time and longer hospital stay for
      this group. The overall complication rate was equivalent in the two groups,
      without differences in the occurrence either of infectious complications or of
      complications related to surgical site. There were no deaths following
      appendectomy in our series. CONCLUSIONS: Laparoscopic appendectomy is safe in the
      elderly population and is not associated with any increase in morbidity. The high
      incidence of complicated appendicitis in elderly patients affects operative time
      and length of hospital stay following laparoscopic appendectomy, and it can also
      lead to an increased rate of conversion to an open procedure. Use of preoperative
      abdominal computerized tomography scan is mandatory in elderly patients to
      provide an early diagnosis and to decrease unnecessary surgical exploration when
      acute appendicitis is suspected.

PMID- 19172346
TI  - Patency rates of cuffed and noncuffed extended polytetrafluoroethylene grafts in
      dialysis access: a prospective, randomized study.
AB  - BACKGROUND: Although autogenous arteriovenous fistulae are the optimal route for
      dialysis access, extended polytetrafluoroethylene (ePTFE) grafts continue to be
      the preferred access for patients without suitable superficial veins. Among the
      common complications related to dialysis grafts, thrombosis due to graft outlet
      stenosis is the most frequently encountered clinical problem. A cuffed graft was
      designed to eliminate the outflow turbulence to reduce outlet stenosis and to
      enhance the clinical patency of ePTFE grafts. We conducted a prospective,
      randomized study to compare the clinical outcomes of cuffed ePTFE grafts and
      noncuffed grafts in dialysis access. METHODS: Between November 2004 and October
      2005, 89 ePTFE grafts were implanted for hemodialysis access in the upper
      extremities of end-stage renal patients. Graft selection was randomized, with
      patients receiving a cuffed graft (Venaflo) or a regular noncuffed graft (Stretch
      Gore-Tex). All patients were monitored for signs of thrombosis or other
      complications. Primary and secondary graft patency was analyzed by using a life
      table analysis, and the log-rank test was applied to compare graft patencies.
      RESULTS: Demographic data for both groups were similar without statistical
      difference. The primary patency rates and secondary patency rates at 12 months
      after implantation were 56% and 91% for cuffed grafts, and 41% and 78% for
      noncuffed grafts, respectively. The cuffed group outperforms the noncuffed group
      regarding primary and secondary patencies statistically. However, the incidence
      of other complications that required further surgery was similar in both groups.
      CONCLUSIONS: This investigation revealed that the cuffed ePTFE graft, which was
      designed to decrease graft outlet stenosis, may enhance the clinical patency
      rates of dialysis grafts.

PMID- 19172347
TI  - Locking, jamming, and ratchet mechanisms of sliding surgical knots topologically
      revisited.
AB  - BACKGROUND: The geometry of lockable, ratchet, or jamming sliding surgical knots
      was assessed to enhance practical and topological understanding of knots among
      surgeons. METHODS: Using a database of more than 100 surgical knots, 29 knots
      that reportedly feature locking, ratchet, or jamming mechanisms were
      topologically assessed for their ability to lock antegradely or retrogradely, to
      lock by assuming their flat geometry, or to jam. RESULTS: Eighteen of the 29
      investigated surgical knots have previously been mistakenly categorized.
      Topologically, the concept of a true ratchet knot is a fallacy. CONCLUSIONS:
      Surgical knots may be consistently classified on the basis of precise and
      detailed definition of various anti-backsliding geometrical characteristics of
      knots.

PMID- 19172348
TI  - "State of the art" in liver resection and living donor liver transplantation: a
      worldwide survey of 100 liver centers.
AB  - BACKGROUND: New strategies have been developed to expand indications for liver
      surgery. The objective was to evaluate the current practice worldwide regarding
      critical liver mass and manipulation of the liver volume. METHODS: A survey was
      sent to 133 liver centers worldwide, which focused on (a) critical liver volume,
      (b) preoperative manipulation of the liver mass, and (c) use of liver biopsy and
      metabolic tests. RESULTS: The overall response rate to the survey was 75%. Half
      of the centers performed more than 100 resections per year; 86% had an associated
      liver transplant program. The minimal remnant liver volume for resection was 25%
      (15-40%) in cases of normal liver parenchyma and 50% (25-90%) in the presence of
      underlying cirrhosis. The minimal remnant liver volume for living donors was 40%
      (30-50%), whereas the accepted graft body weight ratio was 0.8 (0.6-1.2). Portal
      vein occlusion to manipulate the liver volume before resection was performed in
      89% of the centers. CONCLUSIONS: Limits of liver volume and the current practice
      of liver manipulation before resection were comparable among different centers
      and continents. The minimal remnant liver volume in normal liver was 25%, and
      more than 80% of the centers performed portal vein occlusion.

PMID- 19172349
TI  - Partial splenectomy in the management of nonparasitic splenic cysts.
AB  - BACKGROUND: Recognition of the importance of the spleen in immunological function
      and the potential threat of severe postsplenectomy complications have led to the
      development of parenchyma-preserving surgical procedures. The aim of the present
      study was to assess the impact of open splenic partial resection on the
      management of splenic cysts. PATIENTS AND METHODS: From April 2003 to June 2007,
      11 patients with splenic cysts were evaluated. All patients fulfilled the
      criteria for surgical resection. Ten of the patients (6 women and 4 men) 15-42
      years of age (mean: 26.4 years) were subjected to open partial splenectomy. In
      one patient, a centrally located splenic cyst was considered unsuitable for
      partial splenectomy, and the patient therefore underwent total spleen excision.
      Patients with splenic cysts constituted 3.8% of all 290 patients subjected to
      splenectomy during the study period. Spleen parenchyma was cut with the aid of a
      LigaSure instrument. Bleeding from the transected splenic parenchyma was secured
      with argon plasma coagulation and absorbable tape sutures or oxidized cellulose.
      RESULTS: Nine of the ten patients underwent successful partial splenectomy. In
      one patient, insufficient arterial supply to the preserved splenic remnant after
      excision of the upper cyst-containing splenic pole led to total splenectomy. The
      mean operative time was 98 min (range: 85-160 min), and mean blood loss was 106
      ml (55-200 ml). The mean cyst diameter was 9.1 cm (range: 7-17 cm) and weight was
      738 g (range: 230-2,420 g). The postoperative course was uneventful in all cases.
      Pathological examination showed an epithelial cyst in 8 patients and a pseudocyst
      in 2. After a mean follow-up of 26.4 months, the size of the splenic remnant
      constituted, on average, 71% of preoperative spleen size. Moreover, normal
      splenic vein flow was observed. Platelet counts remained within the normal range,
      and no cyst recurrence was observed. There were no infections documented during
      the follow-up period. CONCLUSIONS: Open partial splenectomy is a safe and
      effective method in the management of nonparasitic splenic cysts. It ensures
      complete cyst removal, lack of cyst recurrence, and preservation of the spleen
      functions.

PMID- 19172350
TI  - Single-incision laparoscopic surgery (SILS) for totally extraperitoneal (TEP)
      inguinal hernia repair: first case.

PMID- 19172351
TI  - The frontal cortex is activated during learning of endoscopic procedures.
AB  - BACKGROUND: To date, several training and evaluation systems for endoscopic
      surgery have been developed, such as virtual-reality simulators and box trainers.
      However, despite current advances in these objective assessments, no functional
      brain studies during learning of endoscopic surgical skills have been carried
      out. In the present study, we investigated cortical activation using near
      infrared spectroscopy (NIRS) during endoscopic surgical tasks. STUDY DESIGN: A
      total of 21 right-handed subjects, comprising 4 surgical experts, 4 trainees, and
      13 novices, participated in the study. Suturing and knot-tying tasks were
      performed in a box trainer. Cortical activation was assessed in all subjects by
      task-related changes in hemoglobin (Hb) oxygenation using NIRS. RESULTS: In
      surgical experts and novices with no experience of endoscopic surgical training,
      we found no changes in oxy-Hb, deoxy-Hb or total-Hb levels in any of the frontal
      channels. In surgical trainees and one novice with experience of endoscopic
      surgical training, we found significant increases in oxy-Hb and total-Hb levels
      in most of the frontal channels. There were significant differences in oxy-Hb and
      total-Hb levels in CH-19 between surgical experts and trainees (p = 0.02 for
      both), and between surgical trainees and novices with no experience of endoscopic
      surgical training (p = 0.008 for both). Furthermore, additional training
      increased oxy-Hb levels in the frontal cortex of novices with no experience of
      endoscopic surgical training but had no such effect on surgical experts.
      CONCLUSIONS: The present data suggest that NIRS is a feasible tool for assessing
      brain activation during endoscopic surgical tasks, and may have a large impact on
      the future development of teaching, training, and assessment methods for
      endoscopic surgical skills.

PMID- 19172352
TI  - Short-term outcomes of laparoscopic-assisted distal gastrectomy for gastric
      cancer during a surgeon's learning curve period.
AB  - BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) is gaining wider
      acceptance for treating early gastric cancer (EGC). However, many gastric
      surgeons are still reluctant to perform LADG, mainly because this procedure
      entails a considerable learning curve. We aimed to evaluate the technical
      feasibility and short-term outcomes of performing LADG by a single experienced
      gastric surgeon who initially had no experience with laparoscopic surgery as
      compared with open distal gastrectomy (ODG). METHODS: Between January 2006 and
      December 2007, 177 patients with preoperatively diagnosed EGC located at the
      middle or lower third of the stomach were enrolled; 102 patients underwent LADG,
      4 patients had open conversion, and 71 patients underwent conventional ODG. The
      operative and early postoperative outcomes from a prospective database were
      compared between the two groups. RESULTS: The clinicopathological characteristics
      were similar between the two groups. No operation-related deaths occurred.
      Although operation time was significantly longer for LADG than for ODG, time to
      first flatus was shorter and, consequently, postoperative hospital stay was
      significantly shorter in the LADG group. There was no significant difference in
      the overall complication rates between the two groups. On comparing the early (n
      = 50) and late groups (n = 52) of LADG patients, operation time and postoperative
      hospital stay were shorter and number of retrieved lymph nodes was greater in the
      late group (p < 0.05). Major and minor complications were markedly reduced in the
      late group (p < 0.05). CONCLUSIONS: Although LADG was more time consuming than
      ODG, it was a feasible, safe procedure that accomplished the oncological
      requirements. Postoperative morbidity of LADG was similar to that of ODG, and
      LADG led to faster postoperative recovery. However, LADG should be performed
      carefully to prevent unexpected complications, especially during the early
      learning period.

PMID- 19172353
TI  - Laparoscopic Nissen fundoplication is a good option in patients with abnormal
      esophageal motility.
AB  - BACKGROUND: Patients with gastroesophageal reflux disease (GERD) and abnormal
      esophageal motility are the most controversial subgroup of surgically treated
      patients because of potentially increased risk of postoperative dysphagia. Our
      study aim was to determine if Nissen fundoplication is associated with increased
      postoperative dysphagia in patients with ineffective esophageal motility.
      METHODS: Medical records of all adult (>18 years old) patients who underwent
      laparoscopic Nissen fundoplication for GERD over 8 years were reviewed
      retrospectively. Of the 151 patients, 28 (group A) met manometric criteria for
      abnormal esophageal motility (<30 mmHg mean contractile pressure or <80%
      peristalsis), whereas 63 (group B) had normal esophageal function. Sixty patients
      had no manometric data and were therefore excluded from analysis. Follow-up time
      ranged from 1 month to 5 years. Outcomes (postoperative dysphagia, recurrence of
      GERD symptoms, free of medications) were compared between groups. RESULTS: Group
      A had higher age and American Society of Anesthesiologists (ASA) score (p = 0.016
      and 0.020), but this did not correlate with outcome. Two patients (7.1%) in group
      A and three patients (5.3%) in group B had postoperative dysphagia. When adjusted
      for follow-up time, there was no significant difference between the groups (p =
      0.94). Group B had more cases of recurrent heartburn (10.7% versus 3.6%, p =
      0.039), and more patients in this group were back on medications (21.4% versus
      7.1%, p < 0.05) CONCLUSIONS: This retrospective study found equally low rates of
      dysphagia following Nissen fundoplication regardless of baseline esophageal
      motility. Preoperative esophageal dysmotility therefore does not seem to be a
      contraindication for laparoscopic Nissen fundoplication.

PMID- 19172354
TI  - Robotic-assisted sacrocolpopexy: technique and learning curve.
AB  - BACKGROUND: Laparoscopic sacrocolpopexy (LSCP) offers a minimally invasive
      approach for treating vaginal vault prolapse. The Da Vinci robotic surgical
      system may decrease the difficulty of the procedure. The objective of this study
      was to describe the surgical technique of robotic-assisted sacrocolpopexy (RASCP)
      and evaluate its feasibility, safety, learning curve, and perioperative
      complications. METHODS: Eighty patients underwent RASCP between November 2004 and
      June 2007. Robotic dissection of the planes between the bladder and vagina
      anteriorly and between the vagina and rectum posteriorly was performed. A
      peritoneal incision was made to expose the sacral promontory and extended down to
      the vaginal apex. A Y-shaped mesh was sutured to the anterior and posterior
      surfaces of the vagina. The tail end of the mesh was sutured to the sacral
      promontory. Intracorporeal knot tying was used in all sutures. The peritoneal
      incision was closed to cover the mesh using a running suture. RESULTS: Mean
      operative time was 197.9 [standard deviation (SD) 66.8] min. After completion of
      the first ten cases, mean operative time decreased by 25.4% [64.3 min, 95%
      confidence interval (CI) 16.1-112.4 min, p < 0.01]. Two (2.5%) patients had
      injury to the bladder, one (1.2%) patient had a small bowel injury, and one
      (1.2%) patient had a ureteric injury. Postoperatively, five (6%) patients
      developed vaginal mesh erosion, one (1.2%) patient developed a pelvic abscess,
      and one (1.2%) patient had postoperative ileus. Four (5%) cases were converted to
      laparotomy. Mean follow-up period was 4.8 months (range 1-24 months).
      CONCLUSIONS: RASCP is a feasible procedure with acceptable complication rates and
      short learning curve.

PMID- 19172355
TI  - Perforation into the peritoneal cavity during transanal endoscopic microsurgery
      for rectal cancer is not associated with major complications or oncological
      compromise.
AB  - BACKGROUND: This study was designed to investigate short-term and long-term
      consequences from perforation to the peritoneal cavity during transanal
      endoscopic microsurgery (TEM) for rectal cancer, with special emphasis on local
      recurrence and complications. METHODS: Data from TEM procedures with peritoneal
      perforations were collected from six prospective databases. Patient, procedure,
      and follow-up data were extracted. Participating centers were the United Kingdom
      TEM database, the German TEM database from Mainz, the National Danish TEM
      database, and databases from the three major Norwegian TEM centers. A total of
      888 TEM procedures were registered, and 22 perforations were identified. RESULTS:
      Median age was 82 years. Tumor stages were 14 pT1, 4 pT2, 3 pT3, and 1 pTx. The
      mean tumor size was 4.1 cm. Radical resection was achieved in 17 patients. All
      perforations were handled endoscopically. There were no severe complications and
      no deaths related to the procedure. The mean time of observation was 37 (median
      36; range 3-164) months. Local recurrence occurred in two patients, three
      patients died from the cancer (distant metastasis), and six died from other
      causes. CONCLUSIONS: Breaching the peritoneum during TEM is not associated with
      major short-term complications or long-term oncological consequences provided
      that primary endoscopic repair is undertaken.

PMID- 19172357
TI  - Temporal analysis of tumor heterogeneity and volume for cervical cancer treatment
      outcome prediction: preliminary evaluation.
AB  - In this paper, we present a method of quantifying the heterogeneity of cervical
      cancer tumors for use in radiation treatment outcome prediction. Features based
      on the distribution of masked wavelet decomposition coefficients in the tumor
      region of interest (ROI) of temporal dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) studies were used along with the imaged tumor volume to assess
      the response of the tumors to treatment. The wavelet decomposition combined with
      ROI masking was used to extract local intensity variations in the tumor. The
      developed method was tested on a data set consisting of 23 patients with advanced
      cervical cancer who underwent radiation therapy; 18 of these patients had local
      control of the tumor, and five had local recurrence. Each patient participated in
      two DCE-MRI studies: one prior to treatment and another early into treatment (2-4
      weeks). An outcome of local control or local recurrence of the tumor was assigned
      to each patient based on a posttherapy follow-up at least 2 years after the end
      of treatment. Three different supervised classifiers were trained on
      combinational subsets of the full wavelet and volume feature set. The best
      performing linear discriminant analysis (LDA) and support vector machine (SVM)
      classifiers each had mean prediction accuracies of 95.7%, with the LDA classifier
      being more sensitive (100% vs. 80%) and the SVM classifier being more specific
      (100% vs. 94.4%) in those cases. The K-nearest neighbor classifier performed the
      best out of all three classifiers, having multiple feature sets that were used to
      achieve 100% prediction accuracy. The use of distribution measures of the masked
      wavelet coefficients as features resulted in much better predictive performance
      than those of previous approaches based on tumor intensity values and their
      distributions or tumor volume alone.

PMID- 19172356
TI  - Commissural neurons in the rat ventral cochlear nucleus.
AB  - Commissural neurons connect the cochlear nucleus complexes of both ears. Previous
      studies have suggested that the neurons may be separated into two anatomical
      subtypes on the basis of percent apposition (PA); that is, the percentage of the
      soma apposed by synaptic terminals. The present study combined tract tracing with
      synaptic immunolabeling to compare the soma area, relative number, and location
      of Type I (low PA) and Type II (high PA) commissural neurons in the ventral
      cochlear nucleus (VCN) of rats. Confocal microscopic analysis revealed that 261
      of 377 (69%) commissural neurons have medium-sized somata with Type I axosomatic
      innervation. The commissural neurons also showed distinct topographical
      distributions. The majority of Type I neurons were located in the small cell cap
      of the VCN, which serves as a nexus for regulatory pathways within the auditory
      brainstem. Most Type II neurons were found in the magnocellular core. This
      anatomical dichotomy should broaden current views on the function of the
      commissural pathway that stress the fast inhibitory interactions generated by
      Type II neurons. The more prevalent Type I neurons may underlie slow regulatory
      influences that enhance binaural processing or the recovery of function after
      injury.

PMID- 19172358
TI  - The evolution of tuberculosis virulence.
AB  - The evolution of Mycobacterium tuberculosis presents several challenges for
      public health. HIV and resistance to antimycobacterial medications have
      evolutionary implications for how Mycobacterium tuberculosis will evolve, as
      these factors influence the host environment and transmission dynamics of
      tuberculosis strains. We present an evolutionary invasion analysis of
      tuberculosis that characterizes the direction of tuberculosis evolution in the
      context of different natural and human-driven selective pressures, including
      changes in tuberculosis treatment and HIV prevalence. We find that the evolution
      of tuberculosis virulence can be affected by treatment success rates, the
      relative transmissibility of emerging strains, the rate of reactivation from
      latency among hosts, and the life expectancy of hosts. We find that the virulence
      of tuberculosis strains may also increase as a consequence of rising HIV
      prevalence, requiring faster case detection strategies in areas where the
      epidemics of HIV and tuberculosis collide.

PMID- 19172359
TI  - A compartmental model for activity-dependent dendritic spine branching.
AB  - Dendritic spines are small, mushroom-like protrusions from the arbor of a neuron
      in the central nervous system. Interdependent changes in the morphology,
      biochemistry, and activity of spines have been associated with learning and
      memory. Moreover, post-mortem cortices from patients with Alzheimer's or
      Parkinson's disease exhibit biochemical and physical alterations within their
      dendritic arbors and a reduction in the number of dendritic spines. For over a
      decade, experimentalists have observed perforations in postsynaptic densities on
      dendritic spines after induction of long-term potentiation, a sustained
      enhancement of response to a brief electrical or chemical stimulus, associated
      with learning and memory. In more recent work, some suggest that activity
      dependent intraspine calcium may regulate the surface area of the spine head, and
      reorganization of postsynaptic densities on the surface. In this paper, we
      develop a model of a dendritic spine with the ability to partition its
      transmission and receptor zones, as well as the entire spine head. Simulations
      are initially performed with fixed parameters for morphology to study electrical
      properties and identify parameters that increase efficacy of the synaptic
      connection. Equations are then introduced to incorporate calcium as a second
      messenger in regulating continuous changes in morphology. In the model, activity
      affects compartmental calcium, which regulates spine head morphology. Conversely,
      spine head morphology affects the level of local activity, whether the spines are
      modeled with passive membrane properties, or excitable membrane using Hodgkin
      Huxley kinetics. Results indicate that merely separating the postsynaptic
      receptors on the surface of the spine may add to the diversity of circuitry, but
      does not change the efficacy of the synapse. However, when the surface area of
      the spine is a dynamic variable, efficacy of the synapse may vary continuously
      over time.

PMID- 19172360
TI  - Evolutionary entropy: a predictor of body size, metabolic rate and maximal life
      span.
AB  - Body size of organisms spans 24 orders of magnitude, and metabolic rate and life
      span present comparable differences across species. This article shows that this
      variation can be explained in terms of evolutionary entropy, a statistical
      parameter which characterizes the robustness of a population, and describes the
      uncertainty in the age of the mother of a randomly chosen newborn. We show that
      entropy also has a macroscopic description: It is linearly related to the
      logarithm of the variables body size, metabolic rate, and life span. Furthermore,
      entropy characterizes Darwinian fitness, the efficiency with which a population
      acquires and converts resources into viable offspring. Accordingly, entropy
      predicts the outcome of natural selection in populations subject to different
      classes of ecological constraints. This predictive property, when integrated with
      the macroscopic representation of entropy, is the basis for enormous differences
      in morphometric and life-history parameters across species.

PMID- 19172361
TI  - Incidence of carpal tunnel syndrome in the US military population.
AB  - Carpal tunnel syndrome (CTS) is a common disease. Its epidemiology has been
      evaluated previously, mostly in regional populations or in working groups, with
      an incidence between 1.5 and 3.5 per 1,000 person-years. We studied this
      diagnosis in the US military population, with the hypothesis that this young
      population would have a lower incidence of CTS than previously reported in
      general populations. The Defense Medical Epidemiology Database notes all medical
      encounters for all US military personnel and maintains the number of all
      personnel on active duty each year. We queried the database using the
      International Classification of Diseases, ninth revision, code 354.0 (CTS) and
      analyzed the personnel presenting for initial visits for the years 1998-2006.
      Multivariate Poisson analysis was performed, controlling for rank, gender, age,
      and race. The raw incidence of CTS in the US military was 3.98 per 1,000 person
      years, in a population of 12,298,088 person-years. Females had a significantly
      higher incidence of CTS than males, with an adjusted incidence rate ratio of
      3.29. CTS incidence increased by age, with the age group > or = 40 years having a
      significantly higher incidence. Additionally, military rank was found to be an
      independent risk factor for CTS, with rates higher in senior officer and enlisted
      groups. This suggests that occupational requirements have an effect on CTS within
      the military. We showed a comparable incidence of CTS between the US military and
      general population, with a significantly higher female cohort with a diagnosis of
      CTS. Increased age and advanced rank were risk factors for CTS.

PMID- 19172362
TI  - Tendon graft--ulna fixation in distal radio-ulnar joint stabilisation;
      biomechanical comparison of three graft-bone fixation methods.
AB  - A common distal radio-ulnar joint (DRUJ) stabilisation procedure uses a tendon
      graft running from the lip of the radial sigmoid notch to the ulnar fovea and
      through a bony tunnel to the ulnar shaft, before being wrapped round the distal
      ulna and sutured to itself. Such graft fixation can be challenging and requires a
      considerable tendon length. The graft length could be reduced by fixing the graft
      to the ulna using a bone anchor or interference screw. The aim of this study was
      to compare the strength of three distal ulna graft fixation methods (tendon
      wrapping and suturing, bone anchor and interference screw). Four human cadaveric
      ulnae were used. A tendon strip was run through a tunnel in the distal ulna and
      secured by: (1) wrapping round the shaft and suturing it to itself, (2) a bone
      anchor and (3) an interference screw in the bone tunnel. Load to failure was
      determined using a custom-made apparatus and an Instron machine. Maximum failure
      load was highest for the bone anchor fixation (99.3 +/- 23.7 N) followed by the
      suturing (96.2 +/- 12.1 N), and the interference screw fixation (46.9 +/- 5.6 N).
      There was no significant difference between the tendon suturing and bone anchor
      methods, but the tendon suturing was statistically significantly higher compared
      to the interference screw (P = 0.028). In performing anatomical stabilisation of
      the DRUJ fixation of the tendon graft to the distal ulna with a bone anchor
      provides the most secure fixation. This may make the stabilisation technique less
      demanding and require a smaller tendon graft.

PMID- 19172363
TI  - The Buttazzoni classification of distal radial fractures in adults: interobserver
      and intraobserver reliability.
AB  - Despite the fact that distal radial fracture is the commonest fracture, there is
      a little evidence-based knowledge about the value of its classification to guide
      management and predict prognosis. The available classification systems are either
      complicated or weakly applicable in clinical practice. Older's classification is
      the most reliable, but does not cover all radial fracture types. We evaluated the
      interobserver and intraobserver reliability of a new classification system which
      is a modification of Older's classification covering all radial fracture types.
      Two hundred and thirty-two consecutive adult patients with acute distal radial
      fractures were blindly evaluated according to the new classification by three
      orthopedic surgeons twice with 1-year interval. The interobserver reliability was
      measured using the Fleiss kappa coefficient, and the intraobserver reliability
      was measured using the Cohen's kappa coefficient. The new classification showed
      fair to substantial interobserver and intraobserver reliability, i.e., results
      comparable to the reliability of commonly used classification systems. The
      reliability was better for younger patients and when evaluation was carried out
      by hand-surgery-interested orthopedic surgeons. The new classification system is
      simple, covers all radial fracture types, and has an acceptable reliability.
      Further studies are needed to judge its ability to direct management and predict
      prognosis.

PMID- 19172364
TI  - Physician-physician communication: what's the hang-up?

PMID- 19172365
TI  - The academic quilting bee.
AB  - In medicine, the challenges faced by female faculty members who are attempting to
      achieve academic advancement have been well described. Various strategies have
      been proposed to increase academic productivity to aid the promotion of women in
      medicine. We propose an innovative collaboration strategy that encourages
      completion of an academic writing project. This strategy acknowledges the
      challenges inherent in achieving work-life balance and utilizes a collaborative
      work style with a group of peer physicians. The model is designed to encourage
      the completion and collation of independently prepared sections of an academic
      paper within a setting that emphasizes social networking and collaboration. This
      approach has many similarities to the construction of a quilt during a "quilting
      bee."

PMID- 19172366
TI  - Validation of the Spanish translation of the questionnaire for the obesity
      related problems scale.
AB  - BACKGROUND: The objective of the study was to translate and validate the
      questionnaire for the Obesity-Related Problems Scale (OP) in the Spanish
      language. METHODS: The translation-retranslation procedure and a pilot study were
      first conducted. Then, patients with morbid obesity who were on a waiting list to
      undergo bariatric surgery were selected. The construct validity of the OP scale
      was studied by means of exploratory and confirmatory factor analyses. Item
      convergent and divergent validity were examined. The internal consistency of the
      OP scale, floor and ceiling effects, concurrent validity, and known-group
      validation were also examined. The Short Form 36 and EuroQol-5D questionnaires
      were used to evaluate the concurrent validity. RESULTS: A total of 123
      individuals took part in the field study. Factor analyses and the item convergent
      and divergent validity confirmed the homogeneity of the construct. The Cronbach's
      alpha coefficient was high (0.93), and floor and ceiling effects were small.
      Regarding the OP scale concurrent validity, the majority exceeded the correlation
      coefficient of 0.40, and all correlation coefficients were lower than the
      internal consistency of the OP scale. In relation to the known-group validation,
      significant differences were found in the OP mean scale according to body mass
      index (BMI) and age. Those patients with a higher BMI and younger patients
      reported more obesity-related problems. CONCLUSION: These results confirm that
      this version of the OP scale has been translated and adapted correctly for the
      Spanish language and that it fulfils the psychometric properties required for
      these instruments.

PMID- 19172367
TI  - Chylothorax: unusual complication after laparoscopic gastric banding.
AB  - Laparoscopic adjustable gastric banding is one of the most frequently performed
      bariatric procedures because of its low operative risk and morbidity.
      Postoperative chylothorax has never been reported following bariatric surgery. We
      present the case of a 41-year-old woman who developed a massive right chylothorax
      after a laparoscopic gastric banding, whose lymphogram showed thoracic duct
      disruption. Good outcome was achieved after thoracoscopy approach with duct
      ligation. Although rare, chylothorax is a severe complication, and surgeons must
      be aware of anatomic landmarks. Chyle leak could be under-diagnosed in
      postoperative uncomplicated pleural effusions.

PMID- 19172369
TI  - Resource utilization in clubfoot management.
AB  - Both private and socialized healthcare systems require treatments to be not only
      effective, but also cost-efficient. Although the Ponseti method of clubfoot
      treatment is effective, its cost-effectiveness has not been demonstrated. We
      compared the difference in resource use between two prospective cohorts treated
      for clubfoot by either the Ponseti method or below-knee casting followed by
      primary surgical release in the socialized healthcare system of New Zealand.
      Using these cohorts and US billing data, costs of treating these cohorts in the
      US healthcare system were also calculated. Treatment of initial deformity,
      recurrences, and complications in both cohorts were included in the final
      assessment. Twenty-six patients (40 feet) were enrolled in the Ponseti cohort and
      29 (46 feet) in the primary surgical cohort. For most patients, the Ponseti
      method was more cost-effective than the primary surgical treatment in both
      healthcare systems. The cost of treating both cohorts was lower in the socialized
      system than in the US healthcare system. LEVEL OF EVIDENCE: Level II, prognostic
      study. See the Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 19172368
TI  - Ghrelin and apolipoprotein AIV levels show opposite trends to leptin levels
      during weight loss in morbidly obese patients.
AB  - BACKGROUND: Although bariatric surgery is the most common procedure used to
      induce weight loss in morbidly obese patients, its effect on plasma satiety
      factors (leptin, ghrelin, and apolipoprotein (apo)-AIV) is controversial. The aim
      of this work was to analyze these parameters before and at different times after
      surgery. METHODS: Plasma was obtained from 34 patients before undergoing Roux-en
      Y gastric bypass and during weight loss in the 12 months following surgery.
      RESULTS: Morbidly obese patients had significantly higher values (147%) of leptin
      than normal-weight (NW) persons, while their ghrelin levels were 46% less than
      NW. Apo-AIV levels had approximately the same value in both groups (obese and
      NW). During weight loss, leptin decreased by 75% and ghrelin increased by 78%.
      Both parameters reached values less than or near NW, respectively, at 1 year
      after surgery. During the first month after surgery, apo-AIV plasma levels
      decreased (47%) but later increased and finally returned to preoperative values.
      Apo-AIV levels were correlated negatively with leptin and positively with
      ghrelin. High-density lipoprotein (HDL) levels were positively correlated with
      those of ghrelin and apo-AIV. CONCLUSIONS: During weight loss, plasma leptin and
      ghrelin could be good markers of total fat decrease. Ghrelin could also indicate
      gastric mucous improvement, whereas apo-AIV could indicate the recovery of
      intestinal function. Changes produced in the HDL levels of morbidly obese
      patients during weight loss suggest a decreased risk of coronary disease.

PMID- 19172370
TI  - Social support, social intimacy, and cardiovascular reactions to acute
      psychological stress.
AB  - BACKGROUND: Exaggerated cardiovascular reactions to psychological stress are
      considered a risk factor for cardiovascular morbidity. Social support may reduce
      such risk by attenuating cardiovascular reactivity to stress. PURPOSE: To examine
      the effects of three independent social support variables and their interaction
      on cardiovascular reactivity to acute stress. The variables were stranger or
      friend presence, active supportive or passive presence, and male or female
      presence. METHODS: Cardiovascular reactions to mental arithmetic stress were
      measured in 112 healthy young women tested in one of eight distinct independent
      conditions: active supportive male friend; active supportive female friend;
      passive male friend; passive female friend; active supportive male stranger;
      active supportive female stranger, passive male stranger; and passive female
      stranger. RESULTS: Support from a friend rather than a stranger was associated
      with attenuated blood pressure reactivity, but only when the supporter was a male
      friend. Support from a male stranger or female friend was associated with
      augmented blood pressure reactivity. CONCLUSIONS: This interaction between the
      intimacy and sex of the supporter on cardiovascular reactivity extends the
      findings of previous laboratory studies of social support and can, to an extent,
      be interpreted in terms of the Social Comparison Theory.

PMID- 19172378
TI  - Editorial.

PMID- 19172379
TI  - Distribution of potential suitable hammers and transport of hammer tools and nuts
      by wild capuchin monkeys.
AB  - Selection and transport of objects to use as tools at a distant site are
      considered to reflect planning. Ancestral humans transported tools and tool
      making materials as well as food items. Wild chimpanzees also transport selected
      hammer tools and nuts to anvil sites. To date, we had no other examples of
      selection and transport of stone tools among wild nonhuman primates. Wild bearded
      capuchins (Cebus libidinosus) in Boa Vista (Piaui, Brazil) routinely crack open
      palm nuts and other physically well-protected foods on level surfaces (anvils)
      using stones (hammers) as percussive tools. Here we present indirect evidence,
      obtained by a transect census, that stones suitable for use as hammers are rare
      (study 1) and behavioral evidence of hammer transport by twelve capuchins (study
      2). To crack palm nuts, adults transported heavier and harder stones than to
      crack other less resistant food items. These findings show that wild capuchin
      monkeys selectively transport stones of appropriate size and hardness to use as
      hammers, thus exhibiting, like chimpanzees and humans, planning in tool-use
      activities.

PMID- 19172381
TI  - Myeloid sarcoma in essential thrombocythemia that transformed into acute myeloid
      leukemia.
AB  - A 72-year-old man was diagnosed with essential thrombocythemia (ET) and was
      treated with hydroxyurea for approximately 5 years. He was well until April 2007.
      In May 2007, a slight fall in hemoglobin levels was found. In June 2007, an upper
      endoscopy performed to investigate the cause of anemia showed multiple polypoid
      lesions in the body of the stomach. A gastric biopsy showed a diffuse
      infiltration of very immature cells. Several additional immunohistochemical
      staining showed that the cells were positive for CD13, CD34, CD117, and HLA DR,
      but negative for myeloperoxidase, CD42b, glycophorin, B cell marker, T cell
      marker, cytokeratin and desmin. We finally diagnosed the condition as myeloid
      sarcoma. Subsequently, the patient's ET transformed into acute myeloid leukemia.
      To our knowledge, this is an exceedingly rare event involving a patient with
      essential thrombocythemia.

PMID- 19172380
TI  - Using genetics to understand the dynamics of wild primate populations.
AB  - While much can be learned about primates by means of observation, the slow life
      history of many primates means that even decades of dedicated effort cannot
      illuminate long-term evolutionary processes. For example, while the size of a
      contemporary population can be estimated from field censuses, it is often
      desirable to know whether a population has been constant or changing in size over
      a time frame of hundreds or thousands of years. Even the nature of "a population"
      is open to question, and the extent to which individuals successfully disperse
      among defined populations is also difficult to estimate by using observational
      methods alone. Researchers have thus turned to genetic methods to examine the
      size, structure, and evolutionary histories of primate populations. Many results
      have been gained by study of sequence variation of maternally inherited
      mitochondrial DNA, but in recent years researchers have been increasingly
      focusing on analysis of short, highly variable microsatellite segments in the
      autosomal genome for a high-resolution view of evolutionary processes involving
      both sexes. In this review we describe some of the insights thus gained, and
      discuss the likely impact on this field of new technologies such as high
      throughput DNA sequencing.

PMID- 19172382
TI  - The unfolded protein response during prostate cancer development.
AB  - Accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces the
      unfolded protein response (UPR). The UPR promotes cell survival by adjusting ER
      protein folding capacity but if homeostasis cannot be re-established, apoptosis
      is induced. The execution of life/death decisions is regulated by the three UPR
      branches (IRE1, PERK, ATF6) and their downstream effectors. Events that offset
      the balance of the UPR branches can have devastating consequences, and UPR
      misregulation has been correlated with various diseases, including metabolic and
      neurodegenerative diseases and cancer. In cancer, upregulation of the UPR is
      thought to provide a growth advantage to tumor cells. In contrast to this
      prevailing view, we report here an analysis of data obtained by others indicating
      that all three UPR branches appear selectively down-regulated in mouse models of
      prostate tumorigenesis.

PMID- 19172383
TI  - Radiation-guided targeting of combretastatin encapsulated immunoliposomes to
      mammary tumors.
AB  - PURPOSE: Radiation upregulates expression of endothelial cell adhesion molecules
      providing a potential avenue for targeting drugs to irradiated tissue. Induced
      upregulation of E-selectin can be used to target immunoliposomes to solid tumors.
      The effects of targeting immunoliposomes containing the antivascular drug
      combretastatin disodium phosphate (CA4P) to irradiated mammary tumors were
      investigated in this study. METHODS: Mice bearing transplanted MCa-4 mouse
      mammary tumors were assigned to one of the factorial treatments permuting the
      administration of free CA4P, tumor irradiation, CA4P encapsulated liposomes, and
      CA4P encapsulated immunoliposomes (conjugated with anti-E-selectin). Single and
      fractionated dosing of radiation and/or CA4P was evaluated. RESULTS: For single
      dose treatments the group that received a single dose of radiation plus a single
      dose of immunoliposomes showed a significant delay in tumor growth compared to
      all other treatment groups. Fractionated radiation plus fractionated doses of
      immunoliposomes resulted in further tumor growth delay; however, it was not
      significantly different from other fractionated dose treatment groups that
      combined radiation and CA4P. CONCLUSIONS: Targeting of antivascular drugs to
      irradiated tumors via ligand-bearing liposomes results in significant tumor
      growth delay. This effect can be further potentiated using a fractionated
      irradiation dosing schedule combined with fractionated immunoliposome treatments.

PMID- 19172384
TI  - NF-kappaB decoy oligonucleotides suppress RANTES expression and monocyte
      chemotactic activity via NF-kappaB inactivation in stromal cells of ectopic
      endometrium.
AB  - BACKGROUND: The nuclear factor kappa B (NF-kappaB) pathway is a critical mediator
      of regulated on activation, normal T cell expressed and secreted (RANTES) gene
      regulation and therefore represents a potential target for therapy of
      endometriosis-associated symptoms. OBJECTIVE: The objective of this study was to
      investigate the effect of NF-kappaB decoy oligonucleotides (ODNs) on NF-kappaB
      activation, RANTES expression, and monocyte chemotactic activity in ectopic
      endometrial stromal cells in vitro. METHODS: A specific sandwich enzyme-linked
      immunosorbent assay (ELISA) was used to quantify RANTES expression in ectopic and
      normal endometrial stromal cells stimulated by interleukin (IL)-1beta. Four hours
      after transfection of NF-kappaB decoy ODNs, 10 ng/ml IL-1beta was added to induce
      the ectopic endometrial stromal cells to secrete RANTES. The NF-kappaB
      activation, RANTES expression, and monocyte chemotactic activity in ectopic
      endometrial stromal cells were respectively evaluated by electrophoretic mobility
      shift assay, ELISA, and Boyden chambers. RESULTS: IL-1beta induced significantly
      higher levels (P < 0.05) of RANTES expression in a time-dependent manner in
      ectopic endometrial stromal cells compared with IL-1beta-untreated ectopic and
      normal endometrial stromal cells. The RANTES accounts for the majority (68%) of
      the monocyte chemotactic activity in conditioned media of ectopic endometrial
      stromal cells. In vitro transfection of NF-kappaB decoy ODNs dramatically
      decreased (P < 0.05) the NF-kappaB activation, RANTES expression, and monocyte
      chemotactic activity in IL-1beta-induced ectopic endometrial stromal cells.
      CONCLUSIONS: NF-kappaB decoy ODNs may exert anti-inflammatory effects in ectopic
      endometrial stromal cells via the suppression of NF-kappaB activation, RANTES
      expression, and monocyte chemotactic activity.

PMID- 19172385
TI  - Sociocultural determinants of teenage childbearing among Latinas in California.
AB  - OBJECTIVES: U.S. Latinas have a persistently high rate of teenage childbearing,
      which is associated with adverse outcomes for both mother and child. This study
      was designed to investigate the roles of socioeconomic factors and acculturation
      in teenage childbearing in this population. METHODS: Logistic regression was used
      to analyze the association of measures of acculturation (language spoken at home,
      nativity, and age at immigration) and respondents' parents' education with age at
      first birth in a stratified sample of post-partum women in California. RESULTS:
      The unadjusted odds ratio for teenage birth for Latinas versus non-Latina Whites
      was 5.2 (95% CI 4.1-6.6). Nativity was not significantly associated with teen
      birth, but speaking Spanish at home was positively associated and immigrating at
      a later age was negatively associated with teen birth. Overall, these measures of
      acculturation accounted for 17% (95% CI 8-28%) of the difference in odds of teen
      birth between Latinas and non-Latina Whites. Higher levels of education among
      respondents' parents had differentially protective effects across the
      racial/ethnic groups. Controlling for disparities in respondents' parents'
      education without changing its differential effects across racial/ethnic groups
      reduced the odds ratio for Latinas compared to non-Latina Whites by 30% (95% CI
      14-60%). CONCLUSION: These findings call into question common assumptions about
      the protective effect of acculturation on teen fertility and suggest that
      improving childhood socioeconomic factors among Latinas may decrease teen
      childbearing.

PMID- 19172386
TI  - Low-dimensional, morphologically accurate models of subthreshold membrane
      potential.
AB  - The accurate simulation of a neuron's ability to integrate distributed synaptic
      input typically requires the simultaneous solution of tens of thousands of
      ordinary differential equations. For, in order to understand how a cell
      distinguishes between input patterns we apparently need a model that is
      biophysically accurate down to the space scale of a single spine, i.e., 1 mum. We
      argue here that one can retain this highly detailed input structure while
      dramatically reducing the overall system dimension if one is content to
      accurately reproduce the associated membrane potential at a small number of
      places, e.g., at the site of action potential initiation, under subthreshold
      stimulation. The latter hypothesis permits us to approximate the active cell
      model with an associated quasi-active model, which in turn we reduce by both time
      domain (Balanced Truncation) and frequency-domain (H(2) approximation of the
      transfer function) methods. We apply and contrast these methods on a suite of
      typical cells, achieving up to four orders of magnitude in dimension reduction
      and an associated speed-up in the simulation of dendritic democratization and
      resonance. We also append a threshold mechanism and indicate that this reduction
      has the potential to deliver an accurate quasi-integrate and fire model.

PMID- 19172387
TI  - Common genetic effects of gender atypical behavior in childhood and sexual
      orientation in adulthood: a study of Finnish twins.
AB  - The existence of genetic effects on gender atypical behavior in childhood and
      sexual orientation in adulthood and the overlap between these effects were
      studied in a population-based sample of 3,261 Finnish twins aged 33-43 years. The
      participants completed items on recalled childhood behavior and on same-sex
      sexual interest and behavior, which were combined into a childhood gender
      atypical behavior and a sexual orientation variable, respectively. The phenotypic
      association between the two variables was stronger for men than for women.
      Quantitative genetic analyses showed that variation in both childhood gender
      atypical behavior and adult sexual orientation was partly due to genetics, with
      the rest being explained by nonshared environmental effects. Bivariate analyses
      suggested that substantial common genetic and modest common nonshared
      environmental correlations underlie the co-occurrence of the two variables. The
      results were discussed in light of previous research and possible implications
      for theories of gender role development and sexual orientation.

PMID- 19172388
TI  - Expression of corticosteroid-binding globulin in human astrocytoma cell line.
AB  - Glial tumor cells are known to be sensitive to glucocorticoids (GC) in vivo and
      in vitro. Here we studied the expression of corticosteroid-binding globulin (CBG)
      in the low-grade malignant human astrocytoma cell line 1321N1. CBG was observed
      in cytoplasm of most of these cells with immunocytochemistry. RT-PCR revealed the
      presence of the respective mRNA. Only scattered cells contained nuclear
      immunoreactivity for glucocorticoid receptor as visualized by double
      immunostaining. Immunoreactive CBG could be recovered from the supernatant of
      cultures that had been exposed to 10(-5) M cortisol. Our observations indicate
      the endogenous expression of CBG in 1321N1 cells which may occur independently
      from classical glucocorticoid receptor pathways. Cortisol seems to facilitate
      liberation of CBG in a paracrine manner, perhaps through membrane action of the
      steroid. Effects of adrenal steroids on proliferation and apoptosis of certain
      glial tumors may in part depend on these mechanisms.

PMID- 19172390
TI  - Quantitative analysis of delayed neuronal death in the hippocampal subfields of
      SHRSP and SHR.
AB  - Transient forebrain ischemia and reperfusion induces delayed neuronal death (DND)
      in the hippocampal Cornu Ammonis 1 (CA1) subfield of stroke-prone spontaneously
      hypertensive rat (SHRSP). The vulnerability to DND is potentially related to the
      genetic susceptibility to stroke in this strain. To elucidate the mechanism of
      DND in SHRSP, however, it is essential to establish a method for quantitative
      evaluation of DND, which is not available yet. Male SHRSPs and spontaneously
      hypertensive rats (SHRs) at 12 weeks of age were used in the experiment. The
      bilateral common carotid arteries were surgically occluded with aneurysmal clips
      for 10 min. The brain was taken out 7 days after the experiment of the transient
      ischemia, and was sliced into serial coronal sections. Quantitative estimation of
      the number of viable pyramidal cells in the CA1 and CA2/3 subfields was performed
      based on the stereology with a random and systematic sampling. The transient
      ischemia and reperfusion (TIR) significantly reduced the number of viable
      pyramidal cells in CA1 of SHRSP (61000 +/- 20100 in TIR vs. 128500 +/- 21900 in
      the sham-operation, P < 0.000001 by Student's t-test), while no significant
      difference was observed in SHR (140300 +/- 30800 in TIR vs. 128200 +/- 16700 in
      the sham-operation, P = 0.35). Further analysis revealed a dorsal-ventral
      gradient in the distribution of DND in CA1 of SHRSP with the most severe change
      in the dorsal area. The quantitative measurement using a stereological method is
      useful in the precise evaluation of DND in SHRSP. This method can be applied in
      the studies of effects of medical treatments on the 'ischemia/reperfusion'
      insult.

PMID- 19172389
TI  - Synaptic degeneration of retinal ganglion cells in a rat ocular hypertension
      glaucoma model.
AB  - AIMS: Glaucoma is a common neurodegenerative disease that affects retinal
      ganglion cells (RGCs) and their axons. Little is known of the synaptic
      degeneration involved in the pathophysiology of glaucoma. Here we used an
      experimental ocular hypertension model in rats to investigate this issue.
      METHODS: Elevated intraocular pressure (IOP) was induced by laser coagulation of
      the episcleral and limbal veins. RGCs were retrogradely labeled with Fluoro-Gold
      (FG). The c-fos protein was used as a neuronal connectivity marker. Expression of
      c-fos in the retinas was investigated by immunohistochemistry at 5 days and 2
      weeks after the induction of ocular hypertension. Both surviving RGCs as revealed
      by retrograde FG-labeled and c-fos-labeled RGCs were counted. RESULTS: The c-fos
      protein was mainly expressed in the nuclei and nucleoli of cells in the ganglion
      cell layer and inner nuclear layer in the normal retina. We also confirmed that c
      fos was also expressed in the nuclei and nucleoli of RGCs retrogradely labeled
      with FG. There was no significant RGC loss at 5 days but about 13% RGC loss at 2
      weeks after the induction of ocular hypertension. The number of RGCs expressing c
      fos was significantly lower in the experimental animals at both 5 days and 2
      weeks than normal. CONCLUSION: Our study suggests that there is synaptic
      disconnection for RGCs after ocular hypertension and it may precede the cell
      death in the early stage. It may provide insight into novel therapeutic
      strategies to slow the progress of glaucoma.

PMID- 19172391
TI  - Fibronectin and focal adhesion kinase small interfering RNA modulate rat retinal
      Muller cells adhesion and migration.
AB  - Retinal Muller cells (RMCs) hypertrophy and proliferation play a crucial role in
      epiretinal membrane formation. This study was designed to analyze the effects of
      Fibronectin and specific FAK siRNA in cell adhesion and migration in rat Muller
      cells. RMCs were cultured and identified by GFAP, Vimentin, and GLAST mAb,
      respectively. The cells were planted on dishes coated with Fibronectin at 0, 1,
      5, 10, 50, and 100 microg/ml. The attachment and migration assay was applied to
      characterize the RMCs-Fibronectin interactions. Cell lysis and Western blotting
      were utilized to detect beta(1)-integrin, FAK, and GLAST protein expression. Then
      the cells were treated with FAK siRNA, non-targeting siRNA, and control medium.
      The cell cycle and apoptosis rate was determined by flow cytometry. The
      attachment, migration, and Western blotting assay were repeated. These data
      suggested that almost all the cells expressed GFAP, Vimentin, and GLAST,
      respectively, which ensured most of the harvested cells were RMCs. In attachment
      assay, the A570 values increased significantly with time (F = 1105.439, P <
      0.001) and Fibronectin concentration (F = 424.683, P < 0.001). There were
      significant difference between each Fibronectin concentration in RMCs migration
      (F = 34.703, P < 0.000). The expression ratio of FAK, beta(1)-integrin, and GLAST
      elevated significantly as Fibronectin concentration increased (F = 54.755, P <
      0.000; F = 119.962, P < 0.000; F = 39.287, P < 0.000). The Fibronectin
      pretreatment was settled on 50 microg/ml for siRNA inhibition assays. The
      specific FAK siRNA treatment significantly increased G(0)/G(1) percentage and
      apoptosis rate compared with NT siRNA and control group (F = 11.526, P = 0.009; F
      = 64.772, P < 0.000). The apoptotic rate was significantly suppressed by
      inhibitors of caspase-8 and 3 (F = 10.500, P = 0.011). The A570 values were
      significantly suppressed in FAK siRNA groups compared with NT siRNA and control
      group (F = 154.241, P < 0.000), and the mean migratory cells per view field were
      significantly decreased (F = 10.906, P = 0.001). FAK and GLAST expression ratio
      decreased significantly after FAK siRNA treatment (F = 5.315, P = 0.047; F =
      5.985, P = 0.042). Take together, FAK is involved in beta(1)-integrin mediated
      adhesive signaling and play a critical role in regulating Muller cell adhesion,
      migration, and so far as to glutamate transportation functions.

PMID- 19172392
TI  - Is vitamin E toxic to neuron cells?
AB  - Besides acting as potent free radical scavengers, tocopherols and tocotrienols
      have been known to have non-antioxidant properties such as the involvement of
      alpha-tocopherol (alphaT) in PKC pathway and the anti-cancer properties of gamma
      tocotrienol (gammaT3). This study aims to elucidate whether protective effects
      shown by alphaT and gammaT3 in H(2)O(2)-induced neuron cultures have anti
      apoptotic or pro-apoptotic tendency toward the initiation of neuronal apoptosis.
      H(2)O(2) is used to induce apoptosis in primary cerebellar neuron cultures which
      is attenuated by pretreatment of alphaT or gammaT3 at concentrations < or =10
      microM. Similar to our previous work, gammaT3 was found to be neurotoxic at
      concentrations > or =100 microM, whereas alphaT showed no neurotoxicity. Cellular
      uptake of gammaT3 was higher than that of alphaT. Treating cells simultaneously
      with either gammaT3 or alphaT and with then H(2)O(2) led to higher expression of
      Bax and Bcl-2 than in neurons exposed to H(2)O(2) alone. Analysis of Bcl-2/Bax
      ratio as 'survival index' showed that both pretreatment of gammaT3 and alphaT
      followed by H(2)O(2) increase the 'survival index' of Bcl-2/Bax ratio compared to
      H(2)O(2)-treated cells, while treatment of gammaT3 alone decrease the ratio
      compared to unchanged Bcl2/Bax ratio of similar treatment with alphaT alone.
      Similar treatment of gammaT3 decreased p53 expression and activates p38 MAPK
      phosphorylation, whereas alphaT did not alter its expression compared to H(2)O(2)
      treated cells. Treating neurons with only gammaT3 or alphaT increased the
      expression of Bax, Bcl-2, p53, and p38 MAPK compared to control with gammaT3
      exerting stronger expression for proteins involved than alphaT. In conclusion,
      low doses of gammaT3 and alphaT confer neuroprotection to H(2)O(2)-treated
      neurons via their antioxidant mechanism but gammaT3 has stronger pro-apoptosis
      tendency than alphaT by activating molecules involved in the neuronal apoptotic
      pathway in the absence of H(2)O(2).

PMID- 19172393
TI  - Personality and psychopathology in Flemish referred children: five perspectives
      of continuity.
AB  - The present study investigates five types of continuity of personality and
      internalizing and externalizing problems (i.e., structural, differential, mean
      level, individual-level and ipsative continuity) in a sample of referred children
      and adolescents (N = 114) with a broad variety of psychological problems. Mothers
      were administered a child personality and psychopathology measure, i.e., the
      Hierarchical Personality Inventory for Children [Handleiding hierarchische
      persoonlijkheidsvragenlijst voor kinderen (manual hierarchical personality
      inventory for children). Ghent University, Department of Developmental,
      Personality, and Social Psychology, Ghent, 2005] and the Child Behavior Checklist
      [Handleiding voor de cbcl/4-18: (Manual of the CBCL/4-18), Afdeling Kinder- en
      Jeugdpsychiatrie. Erasmus Universiteit Rotterdam, The Netherlands, 1996] at two
      measurement occasions, with a 26-months interval. Personality was substantially
      stable, paralleling findings for non-referred peers. Internalizing and
      Externalizing Problem Behavior were almost as stable as personality traits,
      suggesting that childhood psychopathology is more persistent than generally
      assumed. Strengths and limitations of the present study and implications for
      further research are discussed.

PMID- 19172394
TI  - Association between epidermal growth factor polymorphism and esophageal squamous
      cell carcinoma susceptibility.
AB  - Genetic factors are known to be important in the development of esophageal
      squamous cell carcinoma (ESCC). Epidermal growth factor (EGF) can activate
      several signaling pathways leading to proliferation, differentiation, and
      tumorigenesis of epithelial tissues by binding with its receptor. Interindividual
      variations in EGF production were genetically contributed to EGF +61 G/A
      polymorphism. The purpose of this study is to investigate the potential
      association between EGF gene polymorphism and ESCC in a Chinese population. In
      this study, we analyzed single nucleotide polymorphism of EGF +61 G/A in 158
      patients with ESCC and 212 age- and sex-matched controls in a Chinese population
      using a polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) strategy and DNA sequencing. The variant genotypes of GA/AA were associated
      with a significantly decreased risk of ESCC compared with the wild-type
      homozygote GG (OR = 0.657, 95% CI: 0.434-0.996). However, no significant
      difference was observed between the EGF +61 G/A polymorphism and the risk of ESCC
      when the analyses were stratified in terms of age, gender, smoking status,
      different clinical stage, and lymph node status. The EGF +61 G/A polymorphism is
      associated with ESCC in a Chinese population. Our data suggests that the EGF gene
      may play a role in the development of ESCC.

PMID- 19172395
TI  - Educational success and adult health: findings from the Chicago longitudinal
      study.
AB  - Growing evidence indicates that education is associated with health, yet we lack
      knowledge about the specific educational experiences influencing health
      trajectories. This study examines the role school factors play in the emergence
      of poor young adult health outcomes for a low-income, minority sample. The
      following research questions are addressed. First, what are the education-based
      predictors of daily tobacco smoking, frequent substance use, depression, and no
      health insurance coverage? Second, do later-occurring school factors explain the
      association between earlier school measures and the outcomes and, if so, what
      pathways account for this mediation effect? Data were derived from the Chicago
      Longitudinal Study, an investigation of a cohort of 1,539 individuals, born
      around 1980, who attended kindergarten programs in the Chicago Public Schools.
      Participants were followed prospectively from early childhood through age 24, and
      study measures were created from various data sources and multiple assessment
      waves. Findings from probit hierarchical regressions with controls for early
      sociodemographic covariates indicated that elementary school socioemotional
      classroom adjustment and high school completion were significantly and negatively
      associated with all four study outcomes. Participation in the Chicago Child
      Parent Center preschool program predicted lower rates of both daily tobacco
      smoking and no health insurance coverage (p < .05). Middle school reading
      achievement was inversely related to depression (p < .01), while middle school
      frustration tolerance was inversely associated with daily tobacco smoking and
      frequent drug use (p < .05). Also, negatively linked to frequent drug use was a
      high school measure of students' expectation to attend college (p < .01). In
      nearly all cases, later-occurring school factors fully mediated significant
      associations between earlier ones and the outcomes. Patterns of mediation were
      explored along with implications of results.

PMID- 19172396
TI  - The Bcl-2 family in autoimmune and degenerative disorders.
AB  - Members of the Bcl-2 family are essential regulators of programmed cell death and
      thus play a major role in the development and function of many tissues. The
      balance between pro-survival and pro-apoptotic members of the family decides
      whether a cell will live or die. This mechanism allows organisms to get rid of
      cells that are no longer needed or have become dangerous. Deregulation of
      apoptosis is a major contributing factor in the development of many diseases. A
      deeper understanding of how the Bcl-2 family proteins orchestrate death in normal
      and pathologic conditions is thus relevant not only for disease etiology, but
      also to try to prevent these various disorders. Experiments with transgenic and
      gene-ablated mice have helped elucidate the function of the different members of
      the Bcl-2 family and their physiological roles. The present review highlights the
      role of Bcl-2 family members in autoimmune and degenerative disorders, with a
      particular focus on the mouse models that have been used to study their function.

PMID- 19172397
TI  - The paradox of autophagy and its implication in cancer etiology and therapy.
AB  - Autophagy is a cellular self-catabolic process in which cytoplasmic constituents
      are sequestered in double membrane vesicles that fuse with lysosomes where they
      are degraded. As this catabolic activity generates energy, autophagy is often
      induced under nutrient limiting conditions providing a mechanism to maintain cell
      viability and may be exploited by cancer cells for survival under metabolic
      stress. However, progressive autophagy can be cytotoxic and autophagy can under
      certain settings substitute for apoptosis in induction of cell death. Moreover,
      loss of autophagy is correlated with tumorigenesis and several inducers of
      autophagy are tumor-suppressor genes. Thus, the relation of autophagy to cancer
      development is complex and depends on the genetic composition of the cell as well
      as on the extra-cellular stresses a cell is exposed to. In this review we
      describe the intricate nature of autophagy and its regulators, particularly those
      that have been linked to cancer. We discuss the multifaceted relation of
      autophagy to tumorigenesis and highlight studies supporting a role for autophagy
      in both tumor-suppression and tumor-progression. Finally, various autophagy
      targeting therapeutic strategies for cancer treatment are presented.

PMID- 19172398
TI  - Monitoring of tumor response to chemotherapy in vivo by a novel small-molecule
      detector of apoptosis.
AB  - Utilization of molecular imaging of apoptosis for clinical monitoring of tumor
      response to anti-cancer treatments in vivo is highly desirable. To address this
      need, we now present ML-9 (butyl-2-methyl-malonic acid; MW = 173), a rationally
      designed small-molecule detector of apoptosis, based on a novel alkyl-malonate
      motif. In proof-of-concept studies, induction of apoptosis in tumor cells by
      various triggers both in vitro and in vivo was associated with marked uptake of
      (3)H-ML-9 administered in vivo, in correlation with the apoptotic hallmarks of
      DNA fragmentation, caspase-3 activation and membrane phospholipid scrambling, and
      with correlative tumor regression. ML-9 uptake following chemotherapy was tumor
      specific, with rapid clearance of the tracer from the blood and other non-target
      organs. Excess of non-labeled "cold" compound competitively blocked ML-9 tumor
      uptake, thus demonstrating the specificity of ML-9 binding. ML-9 may therefore
      serve as a platform for a novel class of small-molecule imaging agents for
      apoptosis, useful for assessment of tumor responsiveness to treatment.

PMID- 19172400
TI  - Physician remuneration methods for family physicians in Canada: expected outcomes
      and lessons learned.
AB  - Canada is a leader in experimenting with alternative, non fee for service
      provider remuneration methods; all jurisdictions have implemented salaries and
      payment models that blend fee for service with salary or capitation components. A
      series of qualitative interviews were held with 27 stakeholders in the Canadian
      health care system to assess the reasons and expectations behind the
      implementation of these payment methods for family physicians, as well as the
      extent to which objectives have been achieved. Results indicate that the main
      reasons are a need to recruit and retain primary care physicians to rural and
      remote regions of the country, and the desire to increase collaboration, care
      continuity, prevention and health promotion. The general perception is that
      positive results have been observed, but problems are not alleviated. Blended
      payments have had some positive effects on preventive care delivery,
      collaboration, and care continuity. Salaries have provided a stable, predictable,
      and high source of income for physicians, thereby improving recruitment and
      retention. The implementation of salaries, however, led to concerns with
      declining physician productivity, and has brought to light a need for improved
      measurement and monitoring systems.

PMID- 19172399
TI  - From cognitive neuroscience to geriatric neuropsychology: what do current
      conceptualizations of the action error handling process mean for older adults?
AB  - The fields of cognitive neuroscience and neuropsychology have contributed an
      extensive corpus of research to the study of error monitoring processes in
      younger adults; however, less is known about error handling in older adults. This
      paper highlights current conceptualizations of error detection and correction in
      healthy and impaired older adult populations. The literature suggests that some
      error handling processes require fewer processing resources than others and may
      be performed relatively automatically. Compared with young adults, older adults
      demonstrate a reduced ability to recognize errors, but exhibit similar rates of
      correction. Older adults diagnosed with a neurodegenerative disease (e.g.
      Alzheimer's disease) show a reduced ability to detect and correct their action
      errors. Thus, neurodegenerative disease processes amplify the impairments in
      error identification associated with normal aging by disrupting both automatic
      and controlled error corrections. The clinical implications of our current
      knowledge are discussed, and directions for future neuropsychological research
      are offered.

PMID- 19172401
TI  - Human arsenic exposure and risk assessment at the landscape level: a review.
AB  - Groundwater contaminated with arsenic (As), when extensively used for irrigation,
      causes potentially long term detrimental effects to the landscape. Such
      contamination can also directly affect human health when irrigated crops are
      primarily used for human consumption. Therefore, a large number of humans are
      potentially at risk worldwide due to daily As exposure. Numerous previous studies
      have been severely limited by small sample sizes which are not reliably
      extrapolated to large populations or landscapes. Human As exposure and risk
      assessment are no longer simple assessments limited to a few food samples from a
      small area. The focus of more recent studies has been to perform risk assessment
      at the landscape level involving the use of biomarkers to identify and quantify
      appropriate health problems and large surveys of human dietary patterns,
      supported by analytical testing of food, to quantify exposure. This approach
      generates large amounts of data from a wide variety of sources and geographic
      information system (GIS) techniques have been used widely to integrate the
      various spatial, demographic, social, field, and laboratory measured datasets.
      With the current worldwide shift in emphasis from qualitative to quantitative
      risk assessment, it is likely that future research efforts will be directed
      towards the integration of GIS, statistics, chemistry, and other dynamic models
      within a common platform to quantify human health risk at the landscape level. In
      this paper we review the present and likely future trends of human As exposure
      and GIS application in risk assessment at the landscape level.

PMID- 19172402
TI  - An effective dietary survey framework for the assessment of total dietary arsenic
      intake in Bangladesh: part-A--FFQ design.
AB  - The accurate assessment of dietary intake patterns is important for the
      determination of total dietary arsenic (As) exposure in As-contaminated regions
      of Bangladesh. Food intake questionnaires are a common means of assessing food
      intake. A food frequency questionnaire (FFQ) was designed to assess the daily
      intake of frequently consumed food items and was successfully implemented to
      assess dietary patterns and intake of the rural populations in 18 villages from
      three Districts of Bangladesh (Comilla, Manikganj Sadar, and Munshiganj). The FFQ
      presented in this paper comprises a complete set of tools which allowed not only
      collection of information on dietary patterns but also information on the spatial
      characteristics of the landscape, socio-demographic indicators, and geographic
      locations of the identified environmental media of the contaminants, which
      resulted in As exposure to humans. The FFQ was designed in three sections: (1)
      general household information, (2) household water and rice information, and (3)
      individual dietary intake of other foods. The dietary intake of other food was
      then further subdivided into five different food subgroups: (i) grain intake,
      (ii) protein intake, (iii) fruit intake (iv), vegetable intake, and (v) dal
      (pulse) intake. During the design and development of the FFQ, emphasis was given
      to the source of food, the frequency (day/week/month) of consumption, and the
      daily amount of food consumed by each adult male, adult female, and child to
      accurately determine the dietary pattern and intake of arsenic in the rural
      population of Bangladesh.

PMID- 19172403
TI  - Current techniques for the study of troponin I phosphorylation in human heart.
AB  - Cardiac troponin I phosphorylation has been shown to be reduced in human heart
      failure and hypertrophic cardiomyopathy using the increasingly popular Pro-Q
      Diamond phosphoprotein gel stain. In this brief report I discuss the use of
      Western immunoblotting, non-equilibrium isoelectric focussing and Pro-Q Diamond
      and introduce phosphate affinity SDS-PAGE using Phos-tag-acrylamide for the
      investigation of troponin I phosphorylation.

PMID- 19172404
TI  - Avian comparative genomics: reciprocal chromosome painting between domestic
      chicken (Gallus gallus) and the stone curlew (Burhinus oedicnemus,
      Charadriiformes)--an atypical species with low diploid number.
AB  - The chicken is the most extensively studied species in birds and thus constitutes
      an ideal reference for comparative genomics in birds. Comparative cytogenetic
      studies indicate that the chicken has retained many chromosome characters of the
      ancestral avian karyotype. The homology between chicken macrochromosomes (1-9 and
      Z) and their counterparts in more than 40 avian species of 10 different orders
      has been established by chromosome painting. However, the avian homologues of
      chicken microchromosomes remain to be defined. Moreover, no reciprocal chromosome
      painting in birds has been performed due to the lack of chromosome-specific
      probes from other avian species. Here we have generated a set of chromosome
      specific paints using flow cytometry that cover the whole genome of the stone
      curlew (Burhinus oedicnemus, Charadriiformes), a species with one of the lowest
      diploid number so far reported in birds, as well as paints from more
      microchromosomes of the chicken. A genome-wide comparative map between the
      chicken and the stone curlew has been constructed for the first time based on
      reciprocal chromosome painting. The results indicate that extensive chromosome
      fusions underlie the sharp decrease in the diploid number in the stone curlew. To
      a lesser extent, chromosome fissions and inversions occurred also during the
      evolution of the stone curlew. It is anticipated that this complete set of
      chromosome painting probes from the first Neoaves species will become an
      invaluable tool for avian comparative cytogenetics.

PMID- 19172405
TI  - Molecular marker suggests rapid changes of sex-determining mechanisms in
      Australian dragon lizards.
AB  - Distribution of sex-determining mechanisms across Australian agamids shows no
      clear phylogenetic segregation, suggesting multiple transitions between
      temperature-dependent (TSD) and genotypic sex determination (GSD). These taxa
      thus present an excellent opportunity for studying the evolution of sex
      chromosomes, and evolutionary transitions between TSD and GSD. Here we report the
      hybridization of a 3 kb genomic sequence (PvZW3) that marks the Z and W
      microchromosomes of the Australian central bearded dragon (Pogona vitticeps) to
      chromosomes of 12 species of Australian agamids from eight genera using
      fluorescence in-situ hybridization (FISH). The probe hybridized to a single
      microchromosome pair in 11 of these species, but to the tip of the long arm of
      chromosome pair 2 in the twelfth (Physignathus lesueurii), indicating a micro
      macro chromosome rearrangement. Three TSD species shared the marked
      microchromosome, implying that it is a conserved autosome in related species that
      determine sex by temperature. C-banding identified the marked microchromosome as
      the heterochromatic W chromosome in two of the three GSD species. However, in
      Ctenophorus fordi, the probe hybridized to a different microchromosome from that
      shown by C-banding to be the heterochromatic W, suggesting an independent origin
      for the ZW chromosome pair in that species. Given the haphazard distribution of
      GSD and TSD in this group and the existence of at least two sets of sex
      microchromosomes in GSD species, we conclude that sex-determining mechanisms in
      this family have evolved independently, multiple times in a short evolutionary
      period.

PMID- 19172408
TI  - Critical coastal issues of Sagar Island, east coast of India.
AB  - Sagar Island, situated in the east coast of India and one of the biggest deltas
      in Sundarban group, faces coastal erosion and degradation of coastal vegetation
      and various natural hazards. Erosion is mainly due to clay mining, wave
      activities, and the impact of river and tidal currents of Muri Ganga and Hugly
      Rivers. Further, the coastal zone of Sagar Island faces increasingly severe
      problems of rapidly growing human population, deteriorating environmental
      quality, and loss of critical habitats. Sagar Island has been victimized several
      times by tropical cyclones and influenced daily by tidal fluctuations. The island
      needs immediate attention on the coastal zone in order to protect the shoreline
      and ecosystem. The capability of satellite remote sensing to provide synoptic,
      repetitive, and multispectral data has proved to be very useful in the inventory
      and monitoring of critical coastal issues. Sagar Island and its environs are
      subjected to both natural and anthropogenic activities that continuously modify
      the region.

PMID- 19172406
TI  - Chromatin condensation in terminally differentiating mouse erythroblasts does not
      involve special architectural proteins but depends on histone deacetylation.
AB  - Terminal erythroid differentiation in vertebrates is characterized by progressive
      heterochromatin formation and chromatin condensation and, in mammals, culminates
      in nuclear extrusion. To date, although mechanisms regulating avian erythroid
      chromatin condensation have been identified, little is known regarding this
      process during mammalian erythropoiesis. To elucidate the molecular basis for
      mammalian erythroblast chromatin condensation, we used Friend virus-infected
      murine spleen erythroblasts that undergo terminal differentiation in vitro.
      Chromatin isolated from early and late-stage erythroblasts had similar levels of
      linker and core histones, only a slight difference in nucleosome repeats, and no
      significant accumulation of known developmentally regulated architectural
      chromatin proteins. However, histone H3(K9) dimethylation markedly increased
      while histone H4(K12) acetylation dramatically decreased and became segregated
      from the histone methylation as chromatin condensed. One histone deacetylase,
      HDAC5, was significantly upregulated during the terminal stages of Friend virus
      infected erythroblast differentiation. Treatment with histone deacetylase
      inhibitor, trichostatin A, blocked both chromatin condensation and nuclear
      extrusion. Based on our data, we propose a model for a unique mechanism in which
      extensive histone deacetylation at pericentromeric heterochromatin mediates
      heterochromatin condensation in vertebrate erythroblasts that would otherwise be
      mediated by developmentally-regulated architectural proteins in nucleated blood
      cells.

PMID- 19172409
TI  - Effect of feeding some West African browse foliages on growth and carcass
      composition in sheep.
AB  - The effect of feeding foliage from Afzelia africana, Pterocarpus erinaceus or
      Khaya senegalensis on growth performance was evaluated using 32 West African
      Djallonke rams of about 8 months of age and with a mean initial body weight (BW)
      of 16.1 kg. The animals were randomly assigned to four groups of 8 animals and
      the experiment lasted for 13 weeks. All the animals received the same amount of
      hay from Andropogon gayanus and maize bran (200 g/day each) and dried foliage ad
      libitum. The control group was fed cottonseed cake in restricted amounts. The
      animals were able to consume higher amounts of A. africana than of P. erinaceus
      and K. senegalensis. There was no significant difference in growth rate between
      sheep offered A. africana or P. erinaceus, 62.9 and 58.8 g/d, respectively, but
      sheep offered K. senegalensis had a lower average daily gain, 48 g/day (P < 0.05)
      due to lower consumption of both energy and crude protein. Animals in the control
      group had the highest growth rate, 95.8 g/day. Sheep offered P. erinaceus and K.
      senegalensis had similar carcass characteristics and dressing percentage but
      lower fasted BW, empty BW, carcass weight and dressing percentage (P < 0.05) than
      sheep offered A. africana. These tree species can provide valuable feed during
      periods of feed shortage in the humid and sub-humid zones.

PMID- 19172407
TI  - Endogenous endothelial cell signaling systems maintain vascular stability.
AB  - The function of the endothelium is to provide a network to allow delivery of
      oxygen and nutrients to tissues throughout the body. This network comprises
      adjacent endothelial cells that utilize adherens junction proteins such as
      vascular endothelial cadherin (VE-cadherin) to maintain the appropriate level of
      vascular permeability. The disruption of VE-cadherin interactions during
      pathologic settings can lead to excessive vascular leak with adverse effects.
      Endogenous cell signaling systems have been defined, which help to maintain the
      proper level of vascular stability. Perhaps the best described system is
      Angiopoietin-1 (Ang-1). Ang-1 acting through its receptor Tie2 generates a well
      described set of signaling events ultimately leading to enhanced vascular
      stability. In this review, we will focus on what is known about additional
      endogenous cell signaling systems that stabilize the vasculature, and using Ang
      1/Tie2 as a model, we will address where our understanding of these additional
      systems is lacking.

PMID- 19172410
TI  - Aromatic L-amino acid decarboxylase deficiency: clinical features, drug therapy
      and follow-up.
AB  - BACKGROUND: Aromatic L-amino acid decarboxylase (AADC) deficiency is a disorder
      of biogenic amine metabolism resulting in generalized combined deficiency of
      serotonin, dopamine and catecholamines. Main clinical features are developmental
      delay, muscular hypotonia, dystonia, oculogyric crises and additional
      extraneurological symptoms. Response to therapy has been variable and
      unsatisfactory; the overall prognosis is guarded. METHODS: To gain more insight
      into this rare disorder we collected clinical and laboratory data of nine German
      patients. All patients were clinically examined by one investigator, and their
      responses to different drug regimes were evaluated by the patients' charts.
      RESULTS: Symptoms were obvious from early infancy. Later, main neurological
      features were truncal muscular hypotonia, hypokinesia, oculogyric crises and
      rigor. Three patients had single seizures. All patients presented distinct
      extraneurological symptoms, such as hypersalivation, hyperhidrosis, nasal
      congestion, sleep disturbances and hypoglycaemia. In CSF all patients revealed
      the pattern typical of AADC with decreased concentrations of homovanillic and 5
      hydroxyindoleacetic acid and elevated concentration of 3-ortho-methyldopa.
      Diagnosis was confirmed by measurement of AADC activity in plasma in all
      patients. Drug regimes consisted of vitamin B6, dopamine agonists, MAO inhibitors
      and anticholinergics in different combinations. No patient achieved a complete
      recovery from neurological symptoms, but partial improvement of mobility and mood
      could be achieved in some. CONCLUSION: AADC deficiency is a severe neurometabolic
      disorder, characterized by muscular hypotonia, dystonia, oculogyric crises and
      additional extraneurological symptoms. Medical treatment is challenging, but a
      systematic trial of the different drugs is worthwhile.

PMID- 19172411
TI  - Abnormal bradykinin signalling in fibroblasts deficient in the PIP(2) 5
      phosphatase, ocrl1.
AB  - The oculocerebrorenal syndrome of Lowe (Lowe syndrome) is an X-linked disorder of
      phosphatidylinositol metabolism characterized by congenital cataracts, renal
      proximal tubulopathy and neurological deficits. The disorder is due to the
      deficiency of the phosphatidylinositol 4,5-bisphosphate (PIP(2)) 5-phosphatase,
      ocrl1. PIP(2) is critical for numerous cellular processes, including cell
      signalling, actin reorganization and protein trafficking, and is chronically
      elevated in patients with Lowe syndrome. The elevation of PIP(2) cells of
      patients with Lowe syndrome provides the unique opportunity to investigate the
      roles of this phospholipid in fundamental cellular processes. We previously
      demonstrated that ocrl1 deficiency causes alterations in the actin cytoskeleton.
      Since actin remodelling is strongly activated by [Ca(+2)], which increases in
      response to IP(3) production, we hypothesized that altered calcium signalling
      might contribute to the observed abnormalities in actin organization. Here we
      report a specific increase in bradykinin-induced Ca(+2) mobilization in Lowe
      fibroblasts. We show that the abnormal bradykinin signalling occurs in spite of
      normal total cellular receptor content. These data point to a novel role for
      ocrl1 in agonist-induced calcium release.

PMID- 19172413
TI  - Heterogeneity of pT3 colorectal carcinomas according to the depth of invasion.
AB  - Colorectal carcinomas (CRCs) infiltrating through the muscularis propria layer
      without infiltration of adjacent structures, organs or the serosa-i.e. the pT3
      tumors, compose the largest subset of large intestinal carcinomas treated by
      surgical resection. They are heterogeneous in terms of prognosis. CRCs treated by
      surgery in a period of 69 months were prospectively classified as pT3a tumors
      (invading to a maximum of 5 mm beyond the muscularis propria) and pT3b tumors
      (invading deeper). Their nodal status, incidence of vascular invasion and the
      presence or absence of distant metastases were analyzed in relation to the depth
      of invasion. Of the 593 CRCs primarily treated by surgery 429 were pT3 tumors.
      CRCs categorized as pT3a had significantly lower rates of nodal involvement (44%
      vs 75%), massive nodal involvement (pN2) (9% vs 39%), venous invasion (17% vs
      30%) and distant metastasis (11% vs 28%) than pT3b tumors. Significant
      differences in these prognostic variables in pT3a and pT3b cancers were observed
      both for carcinomas of the colon and those of the rectum. Such differences were
      not obvious in further 66 ypT3 cases of rectal carcinoma receiving neoadjuvant
      treatment before surgery. Tumors in the pT3a category are associated with a
      better prognostic profile than pT3b tumors. This subdivision might be useful in
      both prognostication and treatment planning.

PMID- 19172412
TI  - Succinic semialdehyde dehydrogenase deficiency: lessons from mice and men.
AB  - Succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder of GABA
      degradation with subsequent elevations in brain GABA and GHB, is a neurometabolic
      disorder with intellectual disability, epilepsy, hypotonia, ataxia, sleep
      disorders, and psychiatric disturbances. Neuroimaging reveals increased T2
      weighted MRI signal usually affecting the globus pallidus, cerebellar dentate
      nucleus, and subthalamic nucleus, and often cerebral and cerebellar atrophy. EEG
      abnormalities are usually generalized spike-wave, consistent with a predilection
      for generalized epilepsy. The murine phenotype is characterized by failure-to
      thrive, progressive ataxia, and a transition from generalized absence to tonic
      clonic to ultimately fatal convulsive status epilepticus. Binding and
      electrophysiological studies demonstrate use-dependent downregulation of GABA(A)
      and (B) receptors in the mutant mouse. Translational human studies similarly
      reveal downregulation of GABAergic activity in patients, utilizing flumazenil-PET
      and transcranial magnetic stimulation for GABA(A) and (B) activity, respectively.
      Sleep studies reveal decreased stage REM with prolonged REM latencies and
      diminished percentage of stage REM. An ad libitum ketogenic diet was reported as
      effective in the mouse model, with unclear applicability to the human condition.
      Acute application of SGS-742, a GABA(B) antagonist, leads to improvement in
      epileptiform activity on electrocorticography. Promising mouse data using
      compounds available for clinical use, including taurine and SGS-742, form the
      framework for human trials.

PMID- 19172414
TI  - Invasive giant prolactinoma with loss of therapeutic response to cabergoline:
      expression of angiogenic markers.
AB  - The present study reports the case of a 70-year-old Caucasian man who was
      referred to the Military Hospital of Buenos Aires for evaluation of a giant
      sellar-extrasellar mass with extension in the right temporal lobe and compression
      of the third ventricle. Patient was initially responsive to cabergoline with
      reduction of prolactin levels and shrinkage of tumor burden for at least 36
      months. Thereafter, prolactin levels and tumor size increased even though
      cabergoline dosage was increased. Transcraneal surgery was performed at 56 months
      of treatment. Prolactin levels and tumor proliferation did not subside and the
      patient died 14 months later. High GH and IGF-I levels were observed in the late
      stages of tumor development, with no evidence of acromegalic features.
      Immunohistochemistry of the excised tumor revealed strong immunoreactivity for
      VEGF and FGF-2, two potent angiogenic factors, and CD31 (an endothelial marker)
      indicating high vascularization of the adenoma.

PMID- 19172416
TI  - The Neuroscience Peer Review Consortium.

PMID- 19172415
TI  - Characteristics, mechanisms of action, and epitope mapping of anti-factor VIII
      antibodies.
AB  - The development of anti-factor VIII (FVIII) antibodies (Abs), also called
      inhibitors, is currently one of the most serious complications arising during the
      treatment of hemophilia A patients. Improved prevention and eradication of these
      Abs remain a challenge both for clinicians and scientists. Numerous studies in
      the literature have reported on their epitope specificity, on their mechanism of
      FVIII inactivation, as well as on the methods used for their detection. In this
      review, we summarize the current knowledge on the nature (isotypes, kinetic
      properties), epitope properties, and mechanisms of action of anti-FVIII Abs.
      Furthermore, we present methods for detection and epitope characterization of
      anti-FVIII Abs with emphasis on the Luminex technique susceptible to facilitate
      the monitoring of changes in the epitope specificity of these Abs.

PMID- 19172417
TI  - Vaccination against human papillomavirus--an impact on preterm delivery?
      Estimations based on literature review.
AB  - OBJECTIVE: Cervical cone excision increases the risk of preterm deliveries.
      Vaccination against human papillomavirus 16/18 (HPV16/18) will probably prevent
      development of high grade cervical intraepithelial neoplasia and thereby reduce
      the need for cervical cone excisions. An HPV16/18 vaccination programme may
      therefore also prevent some preterm deliveries. METHODS: We identified the
      parameters influencing the effect of a HPV16/18 vaccination programme on preterm
      deliveries, and estimated a possible range of preventable deliveries before the
      37th week of pregnancy. The number of preterm deliveries prevented by HPV16/18
      vaccination programme would depend on the number of preterm deliveries related to
      cervical cone excision (extent of the health problem), and the proportion of this
      health problem that could be prevented by a vaccination programme. We obtained
      values on the parameters used in the estimations from the scientific literature.
      RESULTS: If 2% of childbearing women are treated with cervical cone excision,
      between 60 and 220 preterm deliveries/100 000 births may be related to such
      treatment. Close to 60% (between 35 and 128 preterm deliveries) could be
      prevented by an HPV16/18 vaccination programme, if the programme coverage was
      90%. If 4% of women are treated with cone excision, between 70 and 257 preterm
      deliveries/100 000 births could be prevented. CONCLUSION: HPV16/18 vaccination
      programmes may reduce the number of preterm deliveries through reducing the need
      for cone excision.

PMID- 19172418
TI  - Can ultrasound measurements replace digitally assessed elements of the Bishop
      score?
AB  - OBJECTIVE: To compare elements of the Bishop score and corresponding sonographic
      measurements before induction of labor, and assess how predictive factors can be
      used in a clinical setting. DESIGN: Prospective comparative clinical study.
      SETTING: Secondary referral center, university hospital. POPULATION: A total of
      275 women scheduled for induction of labor. METHODS: Fetal head descent to the
      perineum was assessed with transperineal ultrasound. Cervical length, posterior
      angle, and dilatation were evaluated with transvaginal ultrasound followed by
      Bishop score without knowledge of the ultrasound measurements. RESULTS:
      Univariable regression analyses of successful induction were significant for
      digital assessment of cervical dilatation, ultrasound measured fetal head
      perineum distance < or =40 mm, ultrasound measured cervical length < or =25 mm,
      and ultrasound measured posterior cervical angle >90 degrees. After adjusting for
      maternal factors in a multivariable model, estimates were significant for
      previous vaginal birth (OR 5.3; 95% CI 2.1-13.9, p<0.01), but borderline for
      maternal height (OR 1.1; 95% CI 1.0-1.2, p=0.01) and ultrasound measured
      posterior cervical angle >90 degrees (OR 2.6; 95% CI 1.1-6.1, p=0.03). A scoring
      model combining ultrasound measured fetal head-perineum distance, cervical
      length, cervical posterior angle and digitally assessed cervical dilatation,
      discriminated successful and failed induction at 71% (95% CI 61-80%, p<0.01) area
      under the receiver-operating characteristics curve. CONCLUSION: Digital
      assessment of fetal head descent, cervical length and position can possibly be
      replaced with ultrasound measurements. Dilatation is best evaluated with digital
      assessment. Combination of these four factors can predict success of labor
      induction.

PMID- 19172419
TI  - Fetal hemodynamic changes following maternal betamethasone administration in
      pregnancies with fetal growth restriction and absent end-diastolic flow in the
      umbilical artery.
AB  - OBJECTIVES: To examine the effects of betamethasone administration on umbilical
      artery (UA), middle cerebral artery (MCA) and ductus venosus (DV) Doppler flow.
      DESIGN: Longitudinal prospective study. SETTING: Fetal Surveillance Unit,
      Department of Obstetrics and Gynecology, University of Sao Paulo, Sao Paulo,
      Brazil. POPULATION: Thirty-two singleton pregnancies complicated by fetal growth
      restriction with absent end-diastolic flow in the UA. METHODS: Pulsatility index
      (PI) of the UA, MCA and DV was measured from 26 to 34 weeks prior to and within
      24 or 48 hours after starting betamethasone treatment course. Analysis of
      variance for repeated measures was used to determine the changes in the fetal
      hemodynamic Doppler flow following maternal corticosteroid administration. MAIN
      OUTCOME MEASURES: Improvement of UA-PI within 24 hours and DV-PIV (venous
      pulsatility) within 48 hours from the first betamethasone dose. RESULTS: Mean
      gestational age at delivery was 29.3 (+/-1.8) weeks and birthweight was 806.6 (+/
      228.2) g. A reduction in the UA-PI was observed in 29 (90.6%) cases, with return
      of end-diastolic flow in 22 (68.7%). The mean UA-PI were 2.84 (+/-0.52) before
      corticosteroid administration, 2.07 (+/-0.56) within 24 hours and 2.42 (+/-0.75)
      after 48 hours, with a significant difference along the evaluations (p<0.001). No
      significant changes in the MCA Doppler were observed. DV-PIV decreased from 1.06
      (+/-0.23) prior corticosteroids administration to 0.73 (+/-0.16) within 24 hours
      and 0.70 (+/-0.19) after 48 hours (p<0.001). CONCLUSIONS: There was reduction in
      the umbilical artery and in the DV pulsatility indices within 24 hours from
      betamethasone administration that was maintained up to 48 hours.

PMID- 19172420
TI  - Fetal outcome in severe maternal morbidity: too many stillbirths.
AB  - OBJECTIVE: We determined the stillbirth rates among singleton births in Gambian
      hospitals. Contribution of severe obstetric complications was given special
      attention. DESIGN: A multi-center retrospective review. SETTING: Three obstetric
      referral hospitals. SAMPLE: Fetal outcomes in 826 women with severe maternal
      morbidity out of 3,280 singleton deliveries. METHODS: All women with severe
      maternal morbidity reported in the investigated hospitals between January and
      June 2006 were identified and their cases reviewed. For each case, information
      about fetal outcome and the mother's age, parity, obstetric complications and
      delivery mode was abstracted from maternity records. Main outcome measures.
      Stillbirth rates and the impact of health service factors. RESULTS: There were
      excessively high stillbirth rates with an eight-fold increased risk among women
      with severe obstetric complications (310/1,000 births), compared to women without
      complications (51/1,000 births). Hemorrhage, anemia, sepsis and hypertensive
      pregnancy disorders were associated with higher stillbirth rates. Dystocia cases
      had a relatively lower stillbirth rate. In women with severe obstetric
      complications, vaginal delivery was associated with a four-fold increased risk of
      stillbirth compared to cesarean section. CONCLUSION: Severe maternal morbidity
      has significant impact on stillbirth rates. Better access to emergency obstetric
      care and improved intrapartum care will significantly reduce stillbirth rates in
      poor settings of the world, such as The Gambia.

PMID- 19172421
TI  - Infection risk and intrauterine devices.
AB  - For most women, intrauterine contraceptive devices (IUCD) are a safe option.
      Upper genital tract infections (pelvic inflammatory disease, PID) occur when
      pathogenic microorganisms ascend from the cervix and invade the endometrium and
      the fallopian tubes, causing an inflammatory reaction. Evidence-based
      recommendations regarding intrauterine contraception and risk of infection were
      presented at the Congress of the European Society of Contraception, in Prague,
      2008: A clinical history (including sexual history) should be taken as part of
      the routine assessment for intrauterine contraception to identify women at high
      risk of sexually transmitted infections (STI); if appropriate a test should be
      offered; if symptoms or signs are present, appropriate diagnostic tests should be
      done, results awaited, necessary treatment completed, and IUCD insertion
      postponed until resolution. Prophylactic antibiotics are not recommended
      (evidence level II-3). STI screening is not routinely recommended. PID among IUCD
      users is most strongly related to the insertion process and to the background
      risk of STI (evidence level II-2). Conditions which represent an unacceptable
      health risk if an IUCD is inserted (WHO Medical Eligibility Criteria, MEC,
      Categories 3-4) are current PID, current purulent cervicitis, chlamydial or
      gonorrheal infection. For continuation as well as initiation, WHO MEC categories
      3-4 are allotted to women with known pelvic tuberculosis, puerperal sepsis and
      septic abortion.

PMID- 19172422
TI  - Limited knowledge on progestogen-only contraception and risk of venous
      thromboembolism.
AB  - OBJECTIVE: To assess the current knowledge concerning progestogen-only
      contraception (POC) and risks of venous thromboembolism (VTE). DESIGN AND
      SETTING: Systematic review of the literature on observational and analytical
      studies reporting risk estimates for VTE in women exposed to POCs. METHODS AND
      MAIN OUTCOME MEASURES: We performed a computerized literature search in the Pub
      Med, Embase, and the Cochrane Library for studies published between 1966 and
      February 13, 2008. Based on the evaluated studies we calculated an overall risk
      estimate for VTE in association with POC. RESULTS: Four case-control studies and
      one cohort study were included. Of the case-control studies, three reported an
      increased risk and one a decreased risk of VTE. The cohort study found divergent
      results depending on the type of statistical analysis used. None of the results
      was statistically significant. The overall odds ratio for POC-associated VTE in
      the four case-control studies was 1.45 (95% CI=0.92-2.26). CONCLUSIONS: The risk
      of VTE associated with use of POCs is poorly investigated. The slightly elevated
      overall risk estimate might suggest an association between POC and an increased
      risk for VTE. The results must, however, be interpreted with caution due to the
      possibility of residual confounding. Well-designed studies with sufficient
      statistical power to evaluate risks of VTE with POC are warranted.

PMID- 19172423
TI  - Confirmation of tubal patency in hysterosalpingo-contrast sonography by
      transvaginal hydrolaparoscopy.
AB  - OBJECTIVE: To confirm tubal patency in hysterosalpingo-contrast sonography
      (HyCoSy) by transvaginal hydrolaparoscopy (THL). DESIGN: A prospective study.
      SETTING: Infertility clinic at a university hospital. POPULATION: Fifty-six
      infertile women with a history of tubal risk factor(s) who underwent HyCoSy and
      THL between 2003 and 2006. METHODS: After performing HyCoSy, the tubal patency
      was verified by THL. RESULTS: Altogether, 51 women and 101 tubes could be
      examined. Using HyCoSy, 61 of the tubes were considered patent and 40 occluded.
      THL confirmed 82 tubes patent and 19 occluded. Of 61 tubes found to be patent in
      HyCoSy, 60 were also patent in THL. In contrast, of 40 tubes occluded in HyCoSy
      only 18 tubes were confirmed to be occluded by THL. The concordance was 77%. The
      sensitivity of HyCoSy was 95%, the specificity 73%, the negative predictive value
      98% and the positive predictive value 45%. CONCLUSIONS: HyCoSy is a reliable
      method when tubal patency is demonstrated. In cases of suspected tubal occlusion,
      THL is an inexpensive and safe outpatient procedure to exclude benign tubal spasm
      and confirm the presence of true occlusion.

PMID- 19172424
TI  - Invasive prenatal diagnostic practice in Denmark 1996 to 2006.
AB  - The Danish National Board of Health recommended in 2004 routine ultrasound
      scanning in week 12 with nuchal translucency measurement, combined with the
      double test to all pregnant women. Those who were found to have a risk of trisomy
      21 higher than 1:300 were offered amniocentesis or chorionic villus sampling
      (CVS). The total number of pregnancies in Denmark with an invasive prenatal
      procedure decreased from 6,929 in 1996 to 3,103 in 2006, the percentage of CVS
      increased from 45 to 69%, and the percentage of women below 35 years among those
      undergoing invasive procedures increased from 38 to 52%. The mean gestational age
      at which the procedures were done increased--for CVS from week 11 to 13, and for
      amniocentesis from week 16 to 17. We thus achieved to more than double the offer
      of prenatal screening and at the same time reduce the number of invasive
      procedures by 55%.

PMID- 19172425
TI  - Incidence trends of cervical adenocarcinoma in Israeli Jewish women. A population
      based study.
AB  - OBJECTIVE: To assess the trend over time of the relative frequency and incidence
      of adenocarcinoma (AC) in Israeli Jewish women. DESIGN: Register study. SETTING:
      Israel National Cancer Registry. POPULATION: All cases of histologically proven
      invasive cervical cancer diagnosed during two time periods: 1961-1971 and 2002
      2004. METHODS: Calculation of frequencies and incidence rates and comparison by
      the chi2 test and by the Poisson regression model, respectively. MAIN OUTCOME
      MEASURES: Frequency and incidence of AC. RESULTS: There were a total of 532 women
      with a diagnosis of cervical cancer during the first and 434 women during the
      second period (incidence 4.2 and 4.7/100,000, respectively). The total incidence
      rates and frequency rates of AC during the two periods were statistically not
      different. The frequency rate of AC during the second period was significantly
      higher in the 20-29 and the 40-49 age groups and in the North African born than
      in the other ethnic groups. CONCLUSIONS: Our study indicates that except in
      certain age and ethnic groups, the frequency and incidence of AC has not
      significantly altered in Israel over the time periods studied.

PMID- 19172426
TI  - Outcome after endovascular revascularization of atherosclerotic renal artery
      stenosis.
AB  - BACKGROUND: With an aging population, more patients might be treated for
      atherosclerotic renal artery stenosis (ARAS). The goal of this treatment is to
      achieve a dialysis-free life or a well-controlled blood pressure with reduced
      risks of cardiovascular complications. PURPOSE: To analyze the clinical outcome
      of percutaneous transluminal renal artery angioplasty without stenting (PTRA) or
      with stenting (PTRS) for ARAS at one center. MATERIAL AND METHODS: The study
      group comprised 152 patients who underwent 203 PTRA/PTRS. All had hypertension,
      and 45% had azotemia. A retrospective collection of baseline and postprocedural
      number of antihypertensive drugs, blood pressure, and serum creatinine were
      analyzed during a follow-up of 3-18 months. RESULTS: Technical success rate was
      95%, and clinical benefit was seen in 63% of patients. Complications included a
      30-day mortality rate of 1.5%, a total complication rate of 35%, and major
      adverse events in 13%. The major adverse events were highly related to azotemia.
      Major adverse events within 30 days, with permanent disability, were seen in 5%
      and almost exclusively in patients with moderate or severe renal impairment. A
      subgroup analysis of 28 patients with renal duplex resistive index (RI) pre
      PTRA/S and 6 months' follow-up showed a benefit of PTRA/PTRS in 17 (68%) of the
      25 patients with RI <80 and in all three (100%) of the patients with RI >or=80.
      CONCLUSION: Endovascular treatment of ARAS has an excellent technical success
      rate, with a clinical improvement rate of >60%. However, it is associated with a
      considerable complication rate. Serious complications are seen mainly in azotemic
      patients. Predictors of clinical response could not be identified. Renal duplex
      RI is questioned as a predictor of clinical outcome.

PMID- 19172427
TI  - The neurobiology of the dystrophin-associated glycoprotein complex.
AB  - While the function of dystrophin in muscle disease has been thoroughly
      investigated, dystrophin and associated proteins also have important roles in the
      central nervous system. Many patients with Duchenne and Becker muscular
      dystrophies (D/BMD) have cognitive impairment, learning disability, and an
      increased incidence of some neuropsychiatric disorders. Accordingly, dystrophin
      and members of the dystrophin-associated glycoprotein complex (DGC) are found in
      the brain where they participate in macromolecular assemblies that anchor
      receptors to specialized sites within the membrane. In neurons, dystrophin and
      the DGC participate in the postsynaptic clustering and stabilization of some
      inhibitory GABAergic synapses. During development, alpha-dystroglycan functions
      as an extracellular matrix receptor controlling, amongst other things, neuronal
      migration in the developing cortex and cerebellum. Several types of congenital
      muscular dystrophy caused by impaired alpha-dystroglycan glycosylation cause
      neuronal migration abnormalities and mental retardation. In glial cells, the DGC
      is involved in the organization of protein complexes that target water-channels
      to the plasma membrane. Finally, mutations in the gene encoding epsilon
      sarcoglycan cause the neurogenic movement disorder, myoclonus-dystonia syndrome
      implicating epsilon-sarcoglycan in dopaminergic neurotransmission. In this review
      we describe the recent progress in defining the role of the DGC and associated
      proteins in the brain.

PMID- 19172428
TI  - A multi-objective evolutionary algorithm for protein structure prediction with
      immune operators.
AB  - Genetic algorithms (GA) are often well suited for optimisation problems involving
      several conflicting objectives. It is more suitable to model the protein
      structure prediction problem as a multi-objective optimisation problem since the
      potential energy functions used in the literature to evaluate the conformation of
      a protein are based on the calculations of two different interaction energies:
      local (bond atoms) and non-local (non-bond atoms) and experiments have shown that
      those types of interactions are in conflict, by using the potential energy
      function, Chemistry at Harvard Macromolecular Mechanics. In this paper, we have
      modified the immune inspired Pareto archived evolutionary strategy (I-PAES)
      algorithm and denoted it as MI-PAES. It can effectively exploit some prior
      knowledge about the hydrophobic interactions, which is one of the most important
      driving forces in protein folding to make vaccines. The proposed MI-PAES is
      comparable with other evolutionary algorithms proposed in literature, both in
      terms of best solution found and the computational time and often results in much
      better search ability than that of the canonical GA.

PMID- 19172429
TI  - Lateralisation of trunk movements in captive Asian elephants (Elephas maximus).
AB  - Behavioural lateralisation has been widely investigated in vertebrates. Most
      studies in this area have focused on laterality in paired organs such as hands,
      limbs, and eyes. Fewer studies have explored side preferences in unpaired organs
      such as tails or trunks. We investigated laterality of trunk use among captive
      Asian elephants (Elephas maximus), quantifying side preference in four different
      trunk movements: feeding, sand spraying, self-touching, and swinging. We found
      evidence for significant side preference in all four movement categories.
      Variation in the occurrence and direction of side preference was seen both within
      and between individuals but no overall population-level side bias was seen for
      any of the four trunk movements. The strength of side preference in trunk use was
      significantly higher for feeding than for self-touching and swinging. This study
      adds to the very limited data on laterality in unpaired organs generally, and
      elephants' trunks more specifically. In addition it provides novel information
      about directional lateralisation in trunk use across a range of functionally
      distinct contexts.

PMID- 19172430
TI  - Neurocognitive functioning of a child with partial trisomy 6 and monosomy 21.
AB  - This case study describes the neurocognitive presentation of a child with
      identified genetic abnormalities of trisomy 6 and monosomy 21 who was evaluated
      as part of a standard medical protocol for cochlear implantation following
      diagnosis of profound sensorineural hearing loss. This child received
      neurocognitive testing prior to cochlear implantation and approximately 12 months
      post-activation of his cochlear implant. While he has not fully developed oral
      language, his presentation suggested improvement in overall skills since the
      activation of the cochlear implant; however, less than would be expected for a
      typically developing child.

PMID- 19172431
TI  - The relationship between visual orienting and interlimb synchrony in a patient
      with a superior parietal infarction: a case study.
AB  - Much work indicates that parietal cortex mediates the transformation of visual
      information into the motor commands necessary for successful performance of many
      unimanual tasks. Accumulating evidence suggests that parietal cortex also
      mediates the coordination of bimanual movements, during which the natural
      tendency is to couple the limbs temporally. However, the extent to which parietal
      oculomotor and/or visual processes contribute to temporal coupling of the limbs
      during bimanual task performance is unknown. In the current study, we monitored
      the eye movements of a patient with a left parietal infarction as she performed a
      series of bimanual visuomotor tasks. We demonstrate the impact of an ipsilesional
      (leftward) orientation bias on her ability to synchronize the onset of bimanual
      limb movements; the movements were performed in serial fashion, i.e., left limb
      before right, when the patient was permitted to freely shift saccades and the
      visual target cuing the left (ipsilesional) limb movement was presented at
      greater (leftward) eccentricities. Disruption of interlimb synchrony as such was
      not, however, evident when the patient was required to fixate or when visual
      targets were presented at lesser ipsilesional eccentricities. Additionally,
      despite the disruptive influence of oculomotor and visual factors on interlimb
      synchrony, the patient appeared capable of using visual feedback to straighten
      the right (contralesional) limb trajectory, thus improving the spatial component
      of task performance. Results suggest that parietal cortex plays an important role
      in the coordination of limb movements during performance of bimanual visuomotor
      tasks. This role appears to involve orienting gaze or attention to the goals of
      each limb so that the nervous system can synchronize the activity of both limbs
      and thereby ensure successful task completion.

PMID- 19172432
TI  - Emotion, social functioning and activities of daily living in frontotemporal
      dementia.
AB  - Social functioning in FTD is profoundly affected, and forms the basis for the
      clinical diagnosis of the behavioural variant of the disease (bv-FTD). In
      particular, there are deficits in emotional processing, but the inter
      relationship of such deficits to other aspects of social functioning remains
      unclear. We studied patients with bv-FTD (n = 14) and AD (n = 14), and compared
      their performance on a test of emotion recognition with their scores on two carer
      based assessments: the Disability Assessment for Dementia (DAD) of activities in
      daily living (ADL), and the Cambridge Behavioural Inventory (CBI). The bv-FTD
      group had significantly greater impairments in ADLs, and had higher scores on the
      CBI, compared to the AD group. Despite a deficit in emotion recognition,
      particularly involving negative emotions, in the FTD group relative to AD and
      controls, performance on this task did not correlate with ADL ratings which
      instead, correlated highly with carer-rated apathy levels on the CBI. The study
      highlights the multifactorial nature of social dysfunction in FTD which is
      important in the management of these patients and in designing effective
      behavioural and therapeutic interventions. The relationship of emotional
      processing to other aspects of social cognition in FTD is reviewed.

PMID- 19172433
TI  - Exogenous luminal nitric oxide exacerbates esophagus tissue damage in a reflux
      esophagitis model of rats.
AB  - OBJECTIVE: Cytotoxic concentrations of nitric oxide are generated luminally at
      the gastroesophageal junction through the entero-salivary recirculation of
      dietary nitrate in humans. The site of luminal nitric oxide generation shifts to
      the lower esophagus when gastric acid is refluxed into the esophagus. The aim of
      this study was to investigate the influence of persistent administration of
      exogenous nitric oxide on esophageal damage. MATERIAL AND METHODS: 0.1% sodium
      nitrite and/or 1% ascorbic acid was administered in an established rat acid
      refluxed esophagitis model. Co-administration of both reactants in this model is
      thought to induce high concentrations of nitric oxide luminally in the esophagus
      by an acid-catalyzed chemical reaction when refluxed gastric acid is present. The
      tissue damage was evaluated by a macroscopic lesion index and myeloperoxidase
      activity. Nitrotyrosin was assessed immunohistochemically as a footprint of
      peroxynitrite formation. RESULTS: Co-administration of sodium nitrite and
      ascorbic acid induced a 4- to 5-fold increase in the esophageal damage compared
      with baseline reflux esophagitis, while the damage was unchanged when either of
      the reagents alone was given. Nitrotyrosine was strongly stained in the tissue
      from the co-administration. Treatment of superoxide scavengers efficiently
      prevented the exacerbation of esophageal damage by exogenous nitric oxide
      exposure, suggesting an essential role of superoxide in esophageal damage.
      CONCLUSIONS: Exogenous luminal nitric oxide greatly exacerbated the tissue damage
      of reflux esophagitis. Diffusion of the luminal nitric oxide into the adjacent
      superoxide-enriched inflamed tissue of the esophagus could lead to the production
      of the highly toxic agent peroxynitrite, thus causing exacerbation of the
      esophageal damage.

PMID- 19172434
TI  - HIV and HCV discordant injecting partners and their association to drug equipment
      sharing.
AB  - Our objective was to examine the association between HIV and HCV discordant
      infection status and the sharing of drug equipment by injection drug users
      (IDUs). IDUs were recruited from syringe exchange and methadone treatment
      programmes in Montreal, Canada. Characteristics of participants and their
      injecting partners were elicited using a structured questionnaire. Among 159
      participants and 245 injecting partners, sharing of syringes and drug preparation
      equipment did not differ between concordant or discordant partners, although HIV
      positive subjects did not share with HIV-negative injectors. Sharing of syringes
      was positively associated with discordant HIV status (OR=1.85) and negatively
      with discordant HCV status (OR=0.65), but both results were not statistically
      significant. Sharing of drug preparation equipment was positively associated with
      both discordant HIV (OR=1.61) and HCV (OR=1.18) status, but both results were non
      significant. Factors such as large injecting networks, frequent mutual
      injections, younger age, and male gender were stronger predictors of equipment
      sharing. In conclusion, IDUs do not appear to discriminate drug equipment sharing
      partners based at least on their HCV infection status. The results warrant
      greater screening to raise awareness of infection status, post-test counselling
      to promote status disclosure among partners, and skill-building to avoid
      equipment sharing between discordant partners.

PMID- 19172435
TI  - Incidence and risk factors of infection in a single cohort of 110 adults with
      systemic lupus erythematosus.
AB  - Infection is a major cause of mortality in patients with systemic lupus
      erythematosus (SLE). This study describes infectious complications in SLE
      patients and analyzes the risk factors for infection at the time of SLE diagnosis
      and during the course of SLE in a case-control study. Of 110 patients enrolled,
      42 (38%) had at least 1 episode of infectious disease. The incidence of
      infectious disease was 4.4/100 patient-years (py) with a total follow-up duration
      of 954 y. In multivariate analysis, independent predictors of infection at the
      time of SLE diagnosis were an SLE disease activity index (SLEDAI) > 12 (p =
      0.01), C3 levels < 90 mg/dl (p = 0.01) and positive anti-ds DNA antibodies (p <
      0.01). Frequent flare-ups (p = 0.04) and follow-up duration > or =8 y (p = 0.023)
      were also significant risk factors for infectious diseases. It is mandatory to
      closely observe SLE patients with risk factors for developing infectious
      diseases.

PMID- 19172436
TI  - Chlamydia pneumoniae DNA is present in peripheral blood mononuclear cells during
      acute coronary syndrome and correlates with chlamydial lipopolysaccharide levels
      in serum.
AB  - Chlamydia pneumoniae can possibly trigger and maintain inflammation in coronary
      arteries. Chlamydia pneumoniae DNA and chlamydial lipopolysaccharide (cLPS) were
      measured 3 times during a 1-y period in 97 patients with acute coronary syndrome.
      Chlamydia pneumoniae DNA in peripheral blood mononuclear cells was detected in 8
      (8.2%) patients at the initial hospitalization and in 9 (10.6%) patients at 3
      months. One y after the acute coronary syndrome, Chlamydia pneumoniae DNA was not
      found in any patients. Serum cLPS levels were elevated at inclusion, and declined
      significantly during follow-up (1.40 microg/ml; (0.20-2.91), median; (range of
      25th to 75th percentiles) at inclusion, 0.44 microg/ml; (0.00-1.39) at 1 y; ANOVA
      p<0.0001). cLPS levels correlated significantly to Chlamydia pneumoniae DNA
      positivity at 3 months (p=0.003). In conclusion, Chlamydia pneumoniae DNA is
      present during acute coronary syndrome and in the recovery period, but declines
      in stable state, suggesting a role of the bacterium in the acute phase of
      coronary syndrome.

PMID- 19172437
TI  - Relationship between erythrocyte catalase and serum adenosine deaminase
      activities in eclampsia.
AB  - OBJECTIVE: To examine the relationship between antioxidant status and T-cell
      activation in the pathogenesis of eclampsia by measuring the activities of
      erythrocyte catalase, an enzyme of antioxidant mechanism, and serum adenosine
      deaminase (ADA), regarded as a marker of T-cell activation. METHODS: A total of
      60 patients [20 eclamptic (E) pregnant women, 20 healthy pregnant (HP) women and
      20 non-pregnant (NP) women] were included in the study. Maternal venous blood
      samples were obtained from each patient during weeks 28-37 of gestation, and
      biochemical analyses of catalase activity in erythrocytes and ADA activity in
      serum were carried out. RESULTS: Erythrocyte catalase activity was significantly
      lower and serum ADA activity was significantly higher in the E pregnant women
      when compared with the HP women and NP women (P <0.001). No significant
      correlation was observed between erythrocyte catalase activity and serum ADA
      activity. CONCLUSIONS: Erythrocyte catalase and serum ADA activities may at least
      in part contribute to the pathogenesis of eclampsia. However, more studies are
      needed to verify and clarify the relationship between antioxidant status and T
      cell activation in eclampsia.

PMID- 19172438
TI  - Grapefruit juice alters plasma sertraline levels after single ingestion of
      sertraline in healthy volunteers.
AB  - OBJECTIVE: Grapefruit juice contains a number of natural substances that have the
      capacity to inhibit the activity of human cytochrome P450 (CYP) 3A4, CYP1A2, and
      p-glycoprotein. We investigated the effects of grapefruit juice on the
      pharmacokinetics of sertraline in healthy volunteers. METHODS: Eight healthy
      subjects volunteered for the study after providing written informed consent to
      participate. The study used a crossover design with two phases separated by an
      interval of at least 2 weeks. The subjects ingested 250 ml of grapefruit juice or
      250 ml of water 3 times daily for 5 days. On day 6, each subject was given 75 mg
      of sertraline with 250 ml of grapefruit juice or water. Blood samples were taken
      2, 4, 6, 8, 10, 24, and 48 h later. Plasma levels of sertraline were determined
      by high-performance liquid chromatography. RESULTS: Grapefruit juice increased
      the mean peak concentrations in plasma (C(max)) of sertraline from 17.6+/-6.1 to
      29.3+/-11.5 ng/ml (mean+/-SD, P=0.003) and the mean area under the plasma
      sertraline concentration-time curve (AUC) from 0 to infinity of sertraline from
      402.0+/-151.9 to 820.5+/-313.0 h ng/ml (mean+/-SD, P=0.002). CONCLUSION: These
      results suggest that grapefruit juice affects the pharmacokinetics of sertraline.

PMID- 19172439
TI  - Development of 5-HT transporter density and long-term effects of methylphenidate
      in an animal model of ADHD.
AB  - Although stimulants as the treatment of choice are widely prescribed in ADHD,
      little is known about their long-term neurobiological effects. Hence, for the
      first time the present study examined the long-term effects of chronic
      methylphenidate (MPH) administration on striatal 5-hydroxytryptamine transporter
      (5-HTT) densities in an animal model of ADHD. First, it compared the normal
      development of striatal 5-HTT densities of spontaneously hypertensive rats (SHR)
      as an animal model of ADHD and Wistar Kyoto (WKY) rats as controls; binding of
      the highly selective ligand of 5-HTT [(3)H]paroxetine was determined on membrane
      preparations of the striatum of SHR and WKY rats on postnatal days 25, 50, and
      90, i.e. from the time of weaning until adulthood. Second, the long-term effect
      of chronic administration of 2 mg/kg per day MPH at two different developmental
      stages (days 25-39 or 50-64) on the striatal 5-HTT density was examined in both
      rat strains at day 90. Long-term effects of MPH treatment on striatal 5-HTT
      density in adulthood could be ruled out in both healthy (WKY) and "ADHD" rats
      (SHR). But a higher striatal 5-HTT density in older SHR versus WKY rats might
      indicate ADHD specific changes in the 5-HT system that needs further
      investigation not only in animals.

PMID- 19172440
TI  - Quality of life for couples 4-5.5 years after unsuccessful IVF treatment.
AB  - OBJECTIVE: To describe quality of life in men and women who had terminated in
      vitro fertilization (IVF) within the public health system 4-5.5 years previously,
      and for whom treatment did not result in childbirth. DESIGN: Cross-sectional
      study. SETTING: Reproductive Unit, Sahlgrenska University Hospital, Gothenburg,
      Sweden. SAMPLE: Four hundred pairs were invited to participate, 71% accepted and
      68% completed questionnaires. METHODS: Questionnaire study. Study subgroups were
      compared with a control group with children and with each other. MAIN OUTCOME
      MEASURE: Psychological General Well-Being (PGWB), Sense of Coherence (SOC),
      experience of infertility, demographic-socio-economic and health characteristics
      were measured. RESULTS: Surprisingly, 76.7% had or lived together with children;
      39.6% had biological children, 34.8% had adopted and 3.7% were parents to both
      biological and adopted children. No differences were found between the study and
      the control groups, except in SOC which scored lower in the study group. The
      study group with children had a higher PGWB index than the 23.3% without children
      and the controls. SOC scored higher in the subgroup with than those without
      children. Infertility was still a central issue in the subgroup without children.
      CONCLUSION: Despite having undergone unsuccessful IVF within the public health
      system, more than 75% lived with children 4-5.5 years later. This subgroup had a
      better quality of life, compared to those without children. Additional IVF
      treatment may result in increased quality of life.

PMID- 19172441
TI  - The effect of uterine fundal pressure on the duration of the second stage of
      labor: a randomized controlled trial.
AB  - OBJECTIVE: To determine the effect of uterine fundal pressure on shortening the
      second stage of labor and on the fetal outcome. DESIGN: Randomized controlled
      trial. SETTING: Teaching and research hospital. SAMPLE: One hundred ninety-seven
      women between 37 and 42 gestational weeks with singleton cephalic presentation
      admitted to the delivery unit. METHODS: Random allocation into groups with or
      without manual fundal pressure during the second stage of labor. MAIN OUTCOME
      MEASURES: The primary outcome measure was the duration of the second stage of
      labor. Secondary outcome measures were umbilical artery pH, HCO3-, base excess,
      pO2, pCO2 values and the rate of instrumental delivery, severe maternal
      morbidity/mortality, neonatal trauma, admission to neonatal intensive care unit,
      and neonatal death. RESULTS: There were no significant differences in the mean
      duration of the second stage of labor and secondary outcome measures except for
      mean pO2 which was lower and mean pCO2 which was higher in the fundal pressure
      group. Nevertheless, the values still remained within normal ranges and there
      were no neonates with an Apgar score <7 in either of the groups. CONCLUSION:
      Application of fundal pressure on a delivering woman was ineffective in
      shortening the second stage of labor.

PMID- 19172442
TI  - New concepts and trends in vaginal prolapse surgery.
AB  - Despite poor results in prolapse surgery, the operative procedures have basically
      remained unchanged for 100 years. It has been postulated that lifting
      restrictions and other measures of inactivation are crucial for the success. Even
      though most of what is done in prolapse repair is not evidence based, few have
      challenged the prevailing concepts. However, tradition-based policies are now
      being scrutinized and in accordance with other operations, time of
      hospitalization is sharply reduced at many institutions. The reintroduction of
      local anesthesia and sedation offers potential advantages compared to regional-
      or general anesthesia. Although augmentation by foreign material is not
      altogether a new concept, the introduction of commercial kits make mesh
      procedures more standardized, but not necessarily technically more easy to
      perform. As molecular biology provides more and more evidence about the
      importance of the quality of the connective tissue, it is conceivable that
      foreign material in prolapse repair is here to stay. In this period of time it is
      more essential than ever to scientifically document the results of the new
      concepts. In the Nordic countries, where the first registries were set up for
      Tensionfree Vaginal Tape (TVT), a cooperative effort among 53 institutions is
      under way to evaluate mesh repairs in prolapse surgery.

PMID- 19172443
TI  - Management of postpartum hemorrhage by uterine balloon tamponade.

PMID- 19172444
TI  - Pre-pregnancy transabdominal cerclage.
AB  - A consecutive series of 45 women with one or more previous second trimester
      deliveries, who had a pre-pregnancy transabdominal cerclage (TAC) from 1999 to
      July 2007, was followed until January 2008. Within the observation period 50
      pregnancies occurred in 36 women. Seven resulted in first trimester abortions,
      none in second trimester abortions or deliveries, and six were on-going
      pregnancies. In the remaining 37 pregnancies the fetal salvage rate was 100%, and
      cesarean section was performed after 34 weeks (mean 36+5 weeks) in 36 (97%)
      pregnancies. One woman had three successful pregnancies following the procedure.
      No serious complications were associated with the application of TAC. One woman
      had a hysterectomy following cesarean section. Pre-pregnancy TAC is a procedure
      with few complications and excellent outcome. The method may be considered in
      women with a second trimester fetal loss, when cervical incompetence cannot be
      ruled out.

PMID- 19172445
TI  - Villoglandular papillary adenocarcinoma of the uterine cervix: a diagnostic
      challenge.
AB  - Villoglandular papillary adenocarcinoma (VGA) is a rare subtype of cervical
      adenocarcinoma. It tends to appear in younger women and its indolent behavior
      permits fertility-preserving treatments. Pathologically, VGA presents a
      diagnostic challenge. The aim of our study was to evaluate the reliability of
      histological assessment for pre-treatment diagnosis of VGA. The data from the
      outpatient files of 12 patients in whom VGA had been diagnosed were reviewed.
      Median age at diagnosis was 38.8 years (range 27-65). Final pathology results
      confirmed VGA in nine patients. Of these, only two had been correctly diagnosed
      preoperatively, while in three, the initial biopsies were benign or pre
      malignant. In four patients, the biopsy results had been interpreted as an
      invasive malignant tumor necessitating hysterectomy. The final histological
      report on the remaining three patients was invasive cervical adenocarcinoma. We
      conclude that pre-treatment diagnosis should not be based solely on a simple
      punch biopsy because of its low rate of diagnostic accuracy.

PMID- 19172446
TI  - Circulating levels of adiponectin, leptin, and tumour necrosis factor alpha in
      hypertension.
AB  - BACKGROUND: Abnormal adipocyte function is implicated in the coalition of
      multiple cardiovascular risk factors, where aberrant circulating levels of the
      adipose-derived hormones adiponectin, leptin, and tumour necrosis factor (TNF)
      alpha may provide the putative link between hypertension and increased
      cardiovascular risk. The pragmatic utility of these 'adipocytokines' in the
      clinical setting of hypertension is unclear, and we hypothesized a relationship
      of circulating adipocytokines to hypertension, and associated cardiovascular
      morbidity. METHOD: Using a cross-sectional approach, we measured plasma
      adipocytokines in 278 'high-risk' treated hypertensive participants of the Anglo
      Scandinavian Cardiac Outcomes Trial (ASCOT) study (mean (SD) age 62.9 (7.7)
      years), who were compared to 54 newly diagnosed untreated hypertensives (61.3
      (10.9) years) and 55 healthy controls (48.3 (12.3) years). RESULTS: Levels of all
      three adipocytokines were lower amongst treated hypertensives compared to newly
      diagnosed hypertensives and healthy controls (P<0.001 for leptin and
      adiponectin), and varied with gender, co-morbidities (e.g. diabetes,
      cardiovascular disease (CVD), left ventricular hypertrophy) and by treatments
      (e.g. statins and beta-blockade). Levels of adiponectin (P<0.001) and leptin
      (P=0.02) rose in an ordinal fashion with increasing hypertension severity
      (grade). Levels of leptin were associated with diastolic blood pressure in a
      positive fashion (P<0.001). CONCLUSIONS: While hypertension affects adipocytokine
      levels, the clinical interpretation of circulating levels in hypertension is
      confounded by a range of factors. The positive relation between leptin and
      adiponectin with hypertension severity may reflect an underlying adaptive
      response that is attenuated during pharmacological hypertension management.

PMID- 19172447
TI  - The Glasgow outcome scale in vegetative state: a possible source of bias.

PMID- 19172448
TI  - The methodology in the paper by Chambers et al. raises serious questions about
      their conclusions.

PMID- 19172450
TI  - Profiling early outcomes during the transition from hospital to home after brain
      injury.
AB  - PRIMARY OBJECTIVE: To profile early outcomes during the transition from hospital
      to home for individuals with acquired brain injury (ABI) and their family
      caregivers. RESEARCH DESIGN: Prospective longitudinal study with data collected
      at three time points: pre-discharge and 1- and 3-months post-discharge. METHODS
      AND PROCEDURES: Participants included 26 individuals with ABI and 26 family
      caregivers, who were assessed on measures of global functioning, psychosocial
      reintegration, health-related quality-of-life and emotional well-being. Changes
      in outcomes over time and group comparisons were examined using repeated measures
      ANOVAs with relevant post-hoc analyses. RESULTS: Participants typically
      demonstrated improved global functioning and psychosocial reintegration during
      the transition period, with closer alignment of perspectives (i.e. comparisons
      between self-ratings of participants with ABI and ratings of family caregivers)
      at 3-months post-discharge on the occupational activities and living skills
      domains. Additionally, levels of depression and stress reported by participants
      with ABI were observed to increase over time. CONCLUSIONS: Collectively, the
      results highlight the critical nature of the transition phase for psychosocial
      reintegration and emotional adjustment and support the need for holistic
      approaches to transition-specific interventions.

PMID- 19172451
TI  - Shunt implantation in a special sub-group of post-traumatic hydrocephalus-
      patients have normal intracranial pressure without clinical representations of
      hydrocephalus.
AB  - BACKGROUND: Post-traumatic hydrocephalus (PTH) is a frequent complication
      secondary to traumatic brain injury (TBI) and controversy remains over whether to
      perform a shunt placement for patients with normal pressure hydrocephalus when
      the patient is too injured to display symptoms or has atypical symptoms. METHOD:
      A hospital-based retrospective study was performed in patients who developed
      normal pressure hydrocephalus, without atypical symptoms, from January 2004 to
      June 2007. Information regarding patients' demographics, TBI, hydrocephalus and
      outcome was collected. RESULTS: A total of 31 patients were involved in this
      study. At the 12-month follow-up, 20 patients (64.5%) showed clear improvement.
      Among the 10 patients who developed PTH after decompressive craniectomy,
      cranioplasty was performed after shunt implantation and clinical improvement was
      observed in nine patients. Additionally, in this series, the patients' age and
      the severity of hydrocephalus, assessed by CT imaging before shunt placement,
      significantly correlated with improvement. CONCLUSION: Although the effect was
      not definitively established, many patients in the sub-group of PTH patients
      described here would benefit from shunt placement, especially when they
      simultaneously have large cranial defects after surgical decompression and
      underwent cranioplasties after shunt placement. Additionally, younger patients
      and those with less severe hydrocephalus before shunt placement may expect a
      better outcome after shunt placement.

PMID- 19172452
TI  - A longitudinal study of functional magnetic resonance imaging in upper-limb
      hemiplegia after stroke treated with constraint-induced movement therapy.
AB  - PRIMARY OBJECTIVE: To investigate the correlation of cerebral function
      reorganization and functional recovery by using functional magnetic resonance
      imaging (fMRI) with constraint-induced movement therapy (CIMT) for chronic upper
      limb hemiparesis in one subject with stroke. RESEARCH DESIGN: The patient was
      treated with 2 weeks of CIMT and the unaffected upper-limb was restricted by a
      splint for 2 weeks. Clinical measures and functional magnetic resonance imaging
      (fMRI) tests were performed 1 day before the treatment, the day of after the
      treatment and 2 weeks after the treatment. MAIN OUTCOMES: Compared with the
      baseline, Upper Extremity Function Test (UEFT) of the patient's upper limb
      increased by 29.1% and Simple Test for Evaluating Hand Function (STEF) increased
      by 18.4%. Before, after and 2 weeks after the treatment, changes of activation in
      brain by using fMRI were found during the movement of the affected and unaffected
      hand. CONCLUSION: CIMT could significantly improve the upper limb movement
      function of stroke patients and fMRI proved that this kind of change was related
      with the plasticity change of the cerebrum. The motor function of the unaffected
      limb could not be affected when it was restricted and the change of the cerebrum
      excitation area was a transient change.

PMID- 19172453
TI  - Injury and recovery: severe amnestic syndrome following traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To illustrate the clinical course of a patient with a marked
      amnestic syndrome resulting from a closed head injury that had significant
      effects on frontal and thalamic memory structures. METHODS AND PROCEDURES: The
      patient underwent a series of brain imaging investigations (CT and MRI) and
      neuropsychological investigations to determine the severity and course of
      behavioural and cognitive impairments. RESULTS: Three months post-injury, the
      patient demonstrated dense retrograde and anterograde amnesia for auditory-verbal
      and visuo-spatial information, disorientation and confabulation. In contrast,
      memory for faces appeared unimpaired. One month later the patient's behaviour,
      orientation and spatial memory had improved with no concomitant improvement in
      auditory-verbal memory. CONCLUSIONS: The findings indicate that injury to the
      diencephalon manifests in a verbal amnesic syndrome that is anterograde in nature
      if localized in the region of the anterior left thalamus, but leaves a relatively
      intact visual memory. Furthermore, injuries to the frontal and temporal lobes and
      their projections to the diencephalon may be more important in the emergence and
      resolution of retrograde amnesia and disturbances in autobiographical recall than
      previously appreciated.

PMID- 19172454
TI  - The association of red blood cell counts with endothelin-1 in African and
      Caucasian women.
AB  - The literature shows an increase in endothelin-1 with increased levels of
      erythrocytes. There are also indications that inflammation and elevated
      endothelin-1 levels interact with erythropoiesis. In this study, the association
      of erythrocytes and endothelin-1 in women of different ethnicities was
      investigated. Blood pressure, vascular resistance, and C-reactive protein (P =
      0.09) were significantly higher in the African women (n = 102) compared to the
      Caucasian women (n = 115), while arterial compliance was significantly lower in
      the African women with no significant differences for endothelin-1. In single,
      partial, and multiple regression analyses, there was a significant positive
      correlation between the red blood cell count and log endothelin-1 in the
      Caucasians while in the Africans there was a weak negative correlation. This is
      an indication that endothelin-1 might interfere with erythrocyte production in
      Africans with higher levels of inflammation.

PMID- 19172455
TI  - Effects of mistletoe (Viscum album L., Loranthaceae) extracts on arterial blood
      pressure in rats treated with atropine sulfate and hexocycline.
AB  - Acute effects of different extracts of mistletoe stem (Viscum album) were
      investigated on values of arterial blood pressure in Wistar rats. Arterial blood
      pressure was registered by direct method in the left carotid artery and the
      investigated extracts (total ethanol, ether and ethyl acetate) of mistletoe stem
      were administered into the right jugular vein. The total ethanol extract
      exhibited the best effect even on the lowest applied concentration (3.33 x 10(-5)
      mg kg(-1)) and significantly decreased the blood pressure after applied
      concentration 1.00 x 10(-3) mg kg(-1). On the contrary, the ether and ethyl
      acetate extracts exhibited notable activity only by higher administered doses.
      Atropine as a nonselective blocker of muscarinic receptors reduced the
      hypotensive effects of ethanol extract of mistletoe. Hexocycline, a selective
      blocker of muscarine receptors, significantly raised blood pressure and decreased
      the hypotensive effect of ethanol extract of mistletoe on arterial blood pressure
      in rats.

PMID- 19172456
TI  - Endothelial dysfunction in patients with noncomplicated and complicated
      hypertension.
AB  - Endothelial dysfunction plays an important role in the pathogenesis of
      hypertension. Other risk factors of atherosclerosis also affect its development.
      The aim of the study was to assess nitric oxide metabolites concentration
      (nitrites and nitrates No(x)) and endothelin (ET-1) in plasma and cyclic 3,5
      guanosine monophosphate (cGMP) in 24 h-urine collection in patients with
      noncomplicated hypertension without risk factors of atherosclerosis and in
      hypertensive patients with coronary artery disease (CAD). Sixty-eight subjects
      were included in the study (44 men, 24 women), aged 47 +/- 76 years, allotted
      into four groups: I - controls (18 clinically healthy subjects); II - 12 subjects
      with hypertension without risk factors of atherosclerosis; III - 16 subjects with
      hypertension and risk factors of atherosclerosis; and IV - 22 subjects with
      hypertension and CAD. Plasma NO(x) concentration was determined using the Greiss
      method, plasma ET-1 by ELISA, and urine cGMP using the immunoenzymatic method.
      Plasma NO(x) concentration was 14.00 +/- 6.88 micromol/L in group I, in group II 
      18.62 +/- 5.84 micromol, in group III - 9.96 +/- 4.72 micromol/L, and in group
      IV - 8.78 +/- 3.72 micromol/L. Statistically significant differences were between
      groups I and III (p < 0.05) and I and IV (p < 0.04) and groups II and III (p <
      0.01) and II and IV (p < 0.01). The concentration of cGMP in 24 h urine
      collection was in group I - 40 +/- 24 pmol/L; in group II - 54 +/- 41 pmol/L; in
      group III - 38 +/- 32 pmol/L; and in group IV - 42 +/- 36 pmol/L. There were no
      significant differences between the groups. Plasma ET-1 concentration was 3.86 +/
      0.52 pg/mL in group I, in group II - 4.05 +/- 0.71 pg/mL, in group III - 4.22 +/
      0.79 pg/mL and in group IV - 4.38 +/- 0.75 pg/mL. Statistically significant
      differences were between group I and III (p < 0.05), I and IV (p < 0.03), and
      between group II and IV (p < 0.04). Endothelial dysfunction was not found in
      hypertensive patients without a family history of cardiovascular diseases and
      without other risk factors of atherosclerosis. Deterioration of endothelial
      function was observed in patients with hypertension with risk factors of
      atherosclerosis. It was most pronounced in those with CAD.

PMID- 19172457
TI  - Brachial-ankle pulse wave velocity as an early indicator of left ventricular
      diastolic function among hypertensive subjects.
AB  - While increased arterial stiffness is a known risk of cardiovascular disease,
      pulse wave velocity (PWV) is a conventionally adopted index of arterial
      stiffness. However, the relationship between PWV and left ventricular functions
      are not thoroughly evaluated. This cross-sectional study investigated whether PWV
      measurement is an early indicator of left ventricular (LV) dysfunction. A
      noninvasive, volume-plethysmographic apparatus was used to determine blood
      pressure, electrocardiogram, heart sounds, and PWV in 42 consecutively diagnosed
      subjects with hypertension, and 42 sex- and age-matched nonhypertension subjects
      were studied. Arterial stiffness and aortic stiffness were evaluated by brachial
      ankle (b-a) PWV, heart-carotid (h-c) PWV, heart-femoral (h-f) PWV, carotid
      femoral (c-f) PWV, and femoral-ankle (f-a) PWV. Function of LV was estimated by
      tissue Doppler imaging (TDI) echocardiography. Hypertension subjects exhibited
      higher b-a PWV and late diastolic mitral flow velocity values than those of
      nonhypertensive subjects. Pearson correlation analysis revealed that LV diastolic
      function (Em(av)) negatively correlated with c-f PWV and b-a PWV. Multiple linear
      regression analysis indicated that b-a PWV was independently and negatively
      associated with LV diastolic function (Em(av)). Further analysis by stratified
      hypertensive status, the b-a PWV were independently and negatively associated
      with Em(av) in hypertensive subjects (p = 0.004) only. In conclusion, the b-a
      PWV, but not c-f PWV, h-c PWV, h-f PWV, or f-a PWV, is significantly correlated
      with LV diastolic function in hypertensive subjects, indicating that b-a PWV
      involving both central and peripheral components of arterial stiffness may be an
      early indicator of LV dysfunction.

PMID- 19172458
TI  - High prevalence of pulmonary hypertension in homozygous sickle cell patients with
      leg ulceration.
AB  - Pulmonary hypertension is a common complication and is a risk factor for death in
      adult patients with sickle cell disease. Chronic leg ulceration is a major cause
      of morbidity in homozygous sickle cell disease. We aimed to determine prevalence
      of pulmonary hypertension in homozygous sickle cell patients and if there is any
      relation of pulmonary hypertension with leg ulceration. A total of 88 patients,
      asymptomatic for pulmonary hypertension, were enrolled in the study. Doppler
      echocardiography was performed on homozygous sickle cell patients with and
      without leg ulceration. 12 patients (10 male, 2 female) had active ulcer or
      healed scar (group I) and 76 patients (40 male, 36 female) had no active leg
      ulcer or history of (group II). The prevalence of pulmonary hypertension in group
      I and group II were 91.6% (n = 11) and 31.6% (n = 24), respectively (p = 0.0001).
      Patients with leg ulceration had increased left atrium and right ventricular
      diameters at diastole and also had increased left ventricular end-diastolic and
      end-systolic diameters. We determined an increased prevalence of pulmonary
      hypertension in patients with leg ulceration. Patients with homozygous sickle
      cell disease, especially those with leg ulcers should be screened for pulmonary
      hypertension, since pulmonary hypertension is a frequent and generally
      asymptomatic complication and a risk factor of mortality.

PMID- 19172459
TI  - Regulation of angiotensin II type I receptor (AT1R) protein levels in the obese
      Zucker rat kidney and urine.
AB  - Increased renal expression of the angiotensin II, type-1 receptor (AT1R) has been
      associated with increased blood pressure (BP) and progression of renal disease.
      We tested whether common medications used to treat hypertension and the metabolic
      syndrome alter renal AT1R; and whether urine AT1R can be used as a reasonable
      noninvasive marker of renal levels in the obese Zucker rat, a model for human
      metabolic syndrome. Immunoblotting revealed that renal and urinary levels of AT1R
      were significantly higher in obese versus lean rats and correlated (R = 0.62, p <
      0.05). Chronic treatment with BP lowering, candesartan, an AT1R antagonist,
      increased renal levels of AT1R in both lean (282% of lean controls) and obese
      (178% of obese controls) rats, but decreased urine AT1R levels in obese rats (72%
      of obese controls). Similarly, chronic treatment with rosiglitazone (RGZ), a
      peroxisome proliferator activated receptor (subtype gamma) agonist, significantly
      decreased urine (43% of obese controls) but not renal AT1R (105%) in obese rats.
      Blood pressure, measured by radiotelemetry, was significantly correlated in
      untreated and RGZ-treated rats to renal AT1R (R = 0.57, p = 0.0035). Finally,
      high- (4%) and medium- (0.4%) NaCl diets increased excretion of AT1R in obese
      rats to approximately 400% of low- (0.04%) NaCl diet. This effect was markedly
      blunted in lean rats. Overall, we demonstrate increased renal AT1R levels in
      obese rats. Urine AT1R correlated with renal levels only in the untreated state.
      Relative salt-sensitivity of AT1R excretion in obese, relative to lean rats, may
      have implications for both BP and renal disease in the metabolic syndrome.

PMID- 19172460
TI  - Association between pulse pressure and subclinical carotid atherosclerosis in
      normotensive and hypertensive post-menopausal women.
AB  - Pulse pressure, the difference between systolic blood pressure and diastolic
      blood pressure, is associated with cardiovascular diseases. Several studies
      showed that a large pulse pressure is an independent predictor of cardiovascular
      mortality since the increased stiffness augment ascending aortic pulse pressure
      that, in turn, produce wall stress and development of atherosclerosis. A sample
      of 252 post-menopausal women underwent a clinical evaluation and carotid artery
      ultrasound examinations. We measured carotid intimal media thickness--a well
      known atherosclerosis marker. For statistical analysis an unpaired student-test
      and a one-way ANOVA to compare means between the groups and a chi-square test to
      compare the prevalence of variables among the groups were used. Multivariate
      linear regression analysis was used to adjust for confounding variables. The
      carotid intimal media thickness (IMT) was significantly associated to pulse
      pressure in post-menopausal women. The statistically significant association was
      confirmed after adjustment for age, blood pressure, cholesterol, and trygliceride
      levels. Indeed, after subdivision in tertiles of pulse pressure, the IMT in the
      third pulse pressure tertile was significantly higher than in the first tertile.
      A large pulse pressure is an independent risk factor for carotid atherosclerosis
      in post-menopausal women. The pulse pressure could predispose to atherosclerosis
      influencing the nitrix oxide (NO) release or representing an injury to the
      arterial wall. Clinical trials are requested to assess whether a treatment aimed
      at reducing the pulse pressure could better prevent cardiovascular and
      cerebrovascular disease in these subjects.

PMID- 19172461
TI  - A tailored target intervention on influence factors of quality of life in Chinese
      patients with hypertension.
AB  - Studies suggested that hypertension was associated with impaired health-related
      quality of life and it is important to find a proper and feasible management of
      hypertension in the community. This study evaluates the effect of a tailored
      target intervention on influence factors of quality of life in Chinese patients
      with hypertension. A cross-sectional survey was carried out to investigate 644
      patients with hypertension by using the Chinese version of the short form-36, and
      195 patients were screened out to participate in the tailored target
      intervention. Multivariate linear regression analyses showed that age, gender,
      educational level, high intake of fried food, household income, attitude,
      knowledge, blood pressure, symptoms, serious events during the past year,
      duration of hypertension, and number of taking anti-hypertensive medicine were
      significantly correlated with quality of life. Grade-based management by
      community physicians and physical exercise had a positive effect on quality of
      life. After the 6-month intervention, the control rate of hypertension was
      increased from 32.0% to 39.4%, and the mean systolic and diastolic blood pressure
      values were significantly decreased to 137.2 and 85.7 mmHg vs. 140.9 and 87.6
      mmHg at baseline, respectively. The intervention program resulted in overall
      improvement on total score of quality of life and mean scores of all the domains
      except social functioning in patients with hypertension. In view of the influence
      factors of quality of life, taking the tailored target intervention could not
      only improve the quality of life of hypertensive patients, but also effectively
      increase the control rate of hypertension.

PMID- 19172462
TI  - Effects of efonidipine hydrochloride on heart rate and circulatory changes due to
      stress.
AB  - Efonidipine hydrochloride is a dual Ca channel blocker that inhibits T-type Ca
      channels, which are localized in the sinoatrial node and are involved in the
      pacemaker mechanism of the heart, as well as L-type Ca channels. In the present
      study, the effect of efonidipine hydrochloride in inhibiting an increase in heart
      rate along with changes in circulation during mental and physical stress was
      examined using normotensive volunteers. A mental arithmetic test caused
      significant increases in heart rate and blood pressure, which were significantly
      inhibited 3 hours after oral administration of 40 mg of efonidipine hydrochloride
      but not at 1 week after cessation of administration. In contrast, the plasma
      norepinephrine, epinephrine, renin activity, and aldosterone levels following the
      test were unchanged at both 3 hours and 1 week after administration of
      efonidipine hydrochloride. Physical stress in the form of cold by immersing one
      hand in ice water for 2 minutes induced similar increases in the heart rate and
      blood pressure, which were significantly reduced at 3 hours but not at 1 week
      after administration of efonidipine hydrochloride. The plasma levels of the
      humoral factors previously described following the physical stress were unchanged
      at either 3 hours or 1 week after administration of efonidipine hydrochloride.
      These results suggest that efonidipine hydrochloride inhibits increases in heart
      rate and blood pressure due to stress, presumably by blocking T-type Ca channels
      rather than by inhibiting the sympathetic nervous system. Therefore, efonidipine
      hydrochloride is expected to be a Ca antagonist that exhibits a strong
      cardioprotective effect.

PMID- 19172464
TI  - Molecular expression and functional evidence of a drug efflux pump (BCRP) in
      human corneal epithelial cells.
AB  - PURPOSE: Breast Cancer Resistance Protein (BCRP) belongs to the family of efflux
      transporters involved in drug efflux leading to drug resistance. The objective of
      this study was to explore physical barriers for ocular drug absorption and to
      verify the presence and possible role of BCRP as a barrier for ocular drug
      resistance. METHODS: Transfected human corneal epithelial cells (SV40-HCEC) were
      selected as an in vitro model for corneal epithelium with MDCKII-BCRP as positive
      control. [(3)H]-Mitoxantrone ([(3)H]-MTX), which is a proven substrate for
      organic anion transporter like BCRP, was selected as a model drug for functional
      expression studies. Fumetremorgin C (FTC), a known specific inhibitor for BCRP
      and GF120918, an inhibitor for BCRP and P-gp, were added to inhibit BCRP-mediated
      efflux. PGP-4008, a specific inhibitor of P-gp was used to delineate the
      contribution of P-gp. The mRNA extracted from cells was used for RT-PCR analysis
      and gene expression. Membrane fractions of SV40-HCEC and MDCKII-BCRP were used
      for immunoprecipitation followed by Western blot analysis. RESULTS: Efflux was
      inhibited significantly in the presence of FTC and GF120918. Dose-dependent
      inhibition of efflux by BCRP was noticed in SV40-HCEC and MDCKII-BCRP in the
      presence of FTC and GF120918, and the efflux was ATP-dependent. The metabolic
      inhibitor, 2,4-DNP, significantly inhibited efflux. No pH-dependent efflux was
      noticed except at pH 5.5. RT-PCR analysis indicated a unique and distinct band at
      approximately 429 bp, corresponding to BCRP in SV40-HCEC and MDCKII-BCRP cells.
      Western Blot analysis indicated a specific band at approximately 70 kDa in the
      membrane fraction of SV40-HCEC and MDCKII-BCRP cells. CONCLUSIONS: We have
      demonstrated the expression of BCRP in human corneal epithelial cells and, for
      the first time, demonstrated its functional activity leading to drug efflux. RT
      PCR and Western blot analysis further confirmed this finding.

PMID- 19172465
TI  - Pitavastatin attenuates leukocyte-endothelial interactions induced by ischemia
      reperfusion injury in the rat retina.
AB  - PURPOSE: Statins (3-hydroxy-methylglutaryl coenzyme A reductase inhibitors) have
      been shown to lower serum cholesterol levels in clinical use. Moreover, it has
      been reported that statins exert pleiotropic and beneficial effects on vascular
      endothelium. Therefore, we investigated the effects of pitavastatin, a new
      statin, on leukocyte accumulation during ischemia-reperfusion injury. MATERIALS
      AND METHODS: Transient retinal ischemia was induced in Long-Evans rats for 60 min
      by temporal ligation of the optic nerve. Pitavastatin (0.12, 0.35, or 1.1 mg/kg)
      was administered 5 min prior to the induction of retinal ischemia. Leukocyte
      endothelial interactions in the post-ischemic retina were evaluated in vivo with
      acridine orange digital fluorography. The number of rolling leukocytes, number of
      accumulated leukocytes, and diameters of the major retinal artery and vein were
      evaluated. Intercellular adhesion molecule-1 (ICAM-1) mRNA expression in the
      retina was semiquantitatively studied using the RT-PCR method. RESULTS:
      Pitavastatin-treated rats at doses of 0.35 and 1.1 mg/kg showed mild arterial
      narrowing (p < 0.01) and venous dilation (p < 0.01) compared with vehicle-treated
      (ischemic) rats. In rats treated with 0.35 mg/kg pitavastatin, the number of
      rolling leukocytes was significantly reduced by 35.5% (p < 0.01) 12 hr after
      reperfusion compared with that of vehicle-treated rats. With treatment at a dose
      of 0.35 mg/kg pitavastatin, the number of accumulated leukocytes was reduced to
      68.7% (p < 0.01) 24 hr after reperfusion. Moreover, pitavastatin treatment
      significantly reduced ICAM-1 mRNA expression in the retina during ischemia
      reperfusion injury. CONCLUSIONS: Pitavastatin effectively attenuated ischemia
      induced leukocyte-endothelial interactions in the rat retina.

PMID- 19172466
TI  - Femtosecond laser-assisted keratoplasty: laboratory studies in eye bank eyes.
AB  - PURPOSE: To optimize the surgical technique for performing femtosecond laser
      assisted keratoplasty (FLAK) using the IntraLase FS to cut both recipient and
      donor cornea buttons in eye bank globes. METHODS: FLAK was performed in six
      globes and six corneoscleral buttons for each of the following trephination
      patterns: top hat, mushroom, tongue-groove, and vertical. Manual trephination was
      performed as control. The wound integrity was tested in incisions closed with 8
      sutures, 8 sutures with fibrin adhesive, and 16 sutures by measuring the
      intraocular pressure required to produce graft-host wound leakage (IOP(L)). Light
      microscopy (LM) and scanning electron microscopy (SEM) were performed to assess
      cut surface quality and graft-host interface regularity. RESULTS: Mushroom and
      top hat FLAK had significantly higher IOP(L) than vertical or manual trephination
      (p < 0.0001) for wounds closed with 16 sutures. There was no difference in IOP(L)
      between top hat, mushroom, and tongue-groove FLAK in wounds closed with 8 sutures
      with fibrin adhesive (p > 0.75). LM and SEM demonstrated cut surfaces with good
      quality and smooth edges. CONCLUSIONS: These preliminary studies show that FLAK
      produces precise trephination cuts of superior wound strength and stability to
      that of manual trephination. Adjuvant fibrin glue may further improve wound
      integrity.

PMID- 19172467
TI  - Numerical study of the effect of corneal layered structure on ocular
      biomechanics.
AB  - PURPOSE: The study aimed to improve the accuracy of corneal numerical simulation
      by adopting a better representation of the corneal layered structure. The study
      considered both the shear and tensile behavior of the interface surfaces between
      stromal lamellae, and assessed the effect of modeling the cornea's three main
      layers-the epithelium, stroma, and endothelium with their respective material
      properties. METHODS: Twelve human donor corneas were tested to determine the
      behavior of the stroma under surface shear. Numerical models were then built to
      consider the stromal inter-lamellar adhesion, which included the shear behavior
      determined experimentally and the tensile behavior available in the literature.
      They also adopted the distinctive material properties of the epithelium, stroma,
      and endothelium. The numerical models simulated corneal behavior under
      intraocular pressure elevation, concentric anterior pressure, and the conditions
      under tonometry with the Goldmann applanation tonometer. RESULTS: The stress
      strain shear behavior of stromal tissue followed an exponential pattern, with an
      initial low stiffness increasing gradually under higher stresses. This behavior
      was adopted in the numerical simulation to set the level of adhesion between
      stromal layers. Considering that the stromal inter-lamellar adhesion and the
      distinctive material properties of corneal layers had a significant effect in
      simulating the response to concentrated anterior pressures, which cause bending
      of corneal tissue, this was almost unnecessary when predicting the effect of
      intraocular pressure, which put the cornea under membrane tension. CONCLUSIONS:
      The corneal layered structure affects the results of numerical simulations
      especially in problems where the cornea is subjected to bending effects.

PMID- 19172468
TI  - Oxidative stress markers in aqueous humor of patients with senile cataracts.
AB  - PURPOSE: To investigate the levels of oxidative stress markers in human eyes with
      senile cataracts. METHODS: We conducted a retrospective, case-controlled study of
      57 patients with senile cataracts. To assess oxidative stress markers in the eye,
      we measured the enzymatic activities of superoxide dismutase (SOD) and catalase
      (CAT) as well as the total protein levels in aqueous humor. RESULTS: In aqueous
      humor, SOD and CAT activity levels were 0.133 +/- 0.020 and 1.223 +/- 0.081 U/ml,
      respectively; protein levels were 2.372 +/- 0.166 mg/ml (means +/- SEM). We
      observed a significant increase in SOD activity and the protein level in
      progressed nuclear cataracts. No significant age-associated difference in
      antioxidant enzyme levels was detected. CONCLUSION: Significant increases in the
      levels of SOD activity and total protein correlated with the severity of the
      cataract but not with patient age, suggesting that progressed cataract is
      associated with molecules leaking from the lens capsule.

PMID- 19172469
TI  - The effect of the Rho-associated protein kinase inhibitor, HA-1077, in the rabbit
      ocular hypertension model induced by water loading.
AB  - PURPOSE: The aim of this study was to investigate the intraocular pressure (IOP)
      lowering effect of a new anti-glaucoma drug, the Rho-associated protein kinase
      (ROCK) inhibitor, HA-1077, in a rabbit ocular hypertension model. METHODS:
      Experiments were carried out in 18 male New Zealand white rabbits, with ocular
      hypertension induced by water loading. Animals were divided into three groups
      followed by topical administration of 1 mM, 2 mM, and 3 mM HA-1077 in the left
      eye. As a control, phosphate buffered saline was administered in the opposite
      eye. RESULTS: After administration of HA-1077 eye drops, there was a significant
      time- and dose-dependent decrease of the IOP. While minor conjunctival injection
      was seen in a few cases, no abnormalities of the anterior chamber or fundus were
      observed. CONCLUSIONS: This is the first report of the effect of the ROCK
      inhibitor, HA-1077, on the IOP in an ocular hypertension model. Study results
      indicated that HA-1077 has a strong IOP-lowering effect.

PMID- 19172470
TI  - Genetically engineered elastin-like polymer as a substratum to culture cells from
      the ocular surface.
AB  - PURPOSE: To investigate epithelial cell adhesion and proliferation on a newly
      developed elastin-like polymer (ELP) that mimics the functional characteristics
      of extracellular matrices. MATERIALS AND METHODS: A genetically engineered ELP
      with cell attachment sequences was adsorbed onto glass coverslips as 1, 2, or 3
      molecular films. Conjunctival epithelial cells from a human cell line and human
      skin fibroblast cells (as controls) were plated onto coverslips with three
      different substrata: plain glass, Thermanox, and ELP-coated. Cells (10(4)) were
      plated after EDTA- or trypsin-based detachment. To test adhesion, epithelial and
      fibroblast cells were incubated for 4 hr, stained with hematoxylin, and counted.
      To study proliferation, Ki-67-positive epithelial cells were counted after 1, 3,
      and 5 days in culture. Immunostaining for conjunctival and adhesion markers was
      performed. RESULTS: Epithelial cell, but not fibroblast, adhesion on ELP was
      significantly enhanced compared to that of control substrata. Epithelial cells
      detached with EDTA alone adhered significantly better than those detached with
      trypsin. By day 5, epithelial cell proliferation on ELP was significantly greater
      than that on plain glass. Epithelial cells grown on ELP expressed conjunctival
      and adhesion markers. CONCLUSIONS: The recombinant ELP resembling the ocular
      surface extracellular matrix was a suitable substratum to sustain epithelial cell
      attachment and growth. This type of polymer may be suitable for tissue
      engineering to restore vision by reconstructing the ocular surface.

PMID- 19172471
TI  - C5a, but not C3a, increases VEGF secretion in ARPE-19 human retinal pigment
      epithelial cells.
AB  - PURPOSE: We examined the potential for the pro-inflammatory complement proteins
      C5a and C3a to increase VEGF expression in ARPE-19 cells. MATERIALS AND METHODS:
      Expression of complement receptors in ARPE-19 cells was evaluated by RT-PCR. VEGF
      secretion from ARPE-19 cells treated with C5a or C3a was determined by ELISA.
      RESULTS: C5a and C3a receptor, but not C5L2, were detected in human eye tissue
      and ARPE-19 cells. C5a, but not C3a, treatment increased VEGF secretion from ARPE
      19 cells, an effect inhibited by the C5aR antagonist, NDT 9513727. CONCLUSIONS:
      C5a receptor mediates increased VEGF secretion from ARPE-19 cells, suggesting a
      role for the C5a receptor in the pathogenesis of macular degeneration.

PMID- 19172472
TI  - Radioprotective effect of a metalloporphyrin compound in rat eye model.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of the
      antioxidant Mn (III) tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) in
      protecting ocular tissue and retinal microvasculature from radiation damage.
      MATERIALS AND METHODS: 75 rats were treated with Mn TE-2-PyP at 2.5 micro
      g/injection into one eye an hour before proton irradiation. The radiation was
      delivered in a single fraction to total doses of 8 Gray (Gy) or 28 Gy; Rats were
      sacrificed 3 days and 3, 6, 9, and 12 months thereafter for histology and
      quantification of photoreceptor cell populations and retinal capillary changes.
      RESULTS: By 6 months following radiation, there was significant loss of retinal
      outer and inner nuclear layers in eyes receiving radiation only (8 and 28 Gy) (p
      < 0.05) compared to their controls and to the eyes of rats treated with radiation
      plus metalloporphyrin. Retinal microvessel length density decreased significantly
      6 months following 28 Gy (p < 0.05) compared to their controls and to MnTE-2-PyP
      treated rats. By 12 months following irradiation, irradiated eyes showed
      extensive damage to the photoreceptor layer, whereas the eyes of animals
      receiving radiation plus MnTE-2-PyP showed almost no morphological damage. MnTE-2
      PyP treatment also suppressed radiation-induced apoptosis in our study.
      CONCLUSIONS: These results demonstrated that MnTE-2-PyP protected both
      photoreceptors and retinal capillaries from radiation damage, suggesting that
      this metalloporphyrin antioxidant is effective in regulating the damage induced
      by proton radiation.

PMID- 19172473
TI  - Evidencing the modulation of P-glycoprotein at blood-ocular barriers using gamma
      scintigraphy.
AB  - PURPOSE: To evaluate the effect of P-glycoprotein modulation at blood-ocular
      barriers using gamma scintigraphy. METHODS: Ofloxacin, a fluoroquinolone, was
      selected as a substrate to study the drug efflux transporter (P-glycoprotein)
      modulation after labeling with Technetium ((99m)Tc) in rabbits. New Zealand
      albino rabbits were randomized into two groups of 4 each. Group I received
      labeled ofloxacin intravitreally (100 micro Ci) and Group II animals were given
      verapamil intravitreally 15 min before the labeled ofloxacin. Static imaging was
      done at predetermined time, and dynamic images were also taken after 30 min of
      intravitreal injection. RESULTS: The radio-chemical purity of labeled ofloxacin
      was found to be 90-95% with the labeling efficiency of 90%. The static anterior
      planar images of verapamil pre-treated group showed marginal increase in the
      uptake of labeled ofloxacin, and dynamic images showed less systemic pool as
      compared to its control. CONCLUSION: This study further confirms the findings of
      our laboratory regarding the involvement of P-glycoprotein in the intraocular
      disposition of susceptible drugs.

PMID- 19172474
TI  - The effect of soft contact lenses during the measurement of retinal nerve fiber
      layer thickness using optical coherence tomography.
AB  - PURPOSE: To investigate if the measurement of retinal nerve fiber layer (RNFL)
      thickness using optical coherence tomography (OCT) is affected by soft contact
      lens wear. METHODS: This prospective, observational, cross-sectional clinical
      study looked at 66 eyes in 66 patients who usually wear soft contact lenses
      everyday and 36 eyes in 36 patients who did not wear contact lenses during the 6
      months prior to the study. No patients had pre-existing retinal or optic nerve
      pathology or other media opacities that might influence the RNFL thickness. All
      eyes were scanned using the fast RNFL program of the Stratus OCT with and without
      soft contact lenses on. RESULTS: The mean RNFL thickness in eyes with and without
      soft contact lenses was 99.4 +/- 9.7 (SD) microm and 100.8 +/- 10.3 micro m,
      respectively, in contact lens wearers. The mean RNFL thickness in eyes with and
      without soft contact lenses was 102.8 +/- 10.8 microm and 105.3 +/- 9.9 microm,
      respectively, in non-contact lens wearers. The mean RNFL thickness in eyes with
      and without soft contact lenses was significantly different in both groups of
      patients (p = 0.006, p = 0.001, respectively). The average RNFL thickness without
      soft contact lenses was statistically significantly increased in non-contact
      wearers compared with soft contact lens wearers (p = 0.035). CONCLUSIONS: Soft
      contact lenses may affect the measurement of RNFL thickness using OCT. It is
      recommended that clinicians be careful in measuring RNFL thickness using OCT with
      myopic patients using soft contact lenses.

PMID- 19172476
TI  - Paying for assistive technology: a study of Hispanics.
AB  - PURPOSE: The purpose of this study is to learn about the methods that Hispanics
      utilise to pay for assistive technology (AT) and how these compare with a
      National sample of non-Hispanic participants who answered the same survey in a
      previous project. METHOD: This secondary analysis combined two studies - a
      National Study and a targeted study of Hispanics - a follow-up study that
      purposively sought out Hispanics, due to their lower representation in the
      national sample. RESULTS: This study found that Hispanics pay for AT out of their
      own pocket or relied on extended family rather than government programmes. The
      study also found that Hispanics utilised private insurance less than their
      counterparts in the National study. CONCLUSIONS: This study raises questions
      about the reach of government programmes, meant to enhance the access of
      underrepresented groups to AT, established by the AT legislation. Further studies
      are needed to explore whether participants are not accessing this programmes or
      are failing to identify them as resources.

PMID- 19172475
TI  - Use of cognitive aids and other assistive technology by individuals with multiple
      sclerosis.
AB  - PURPOSE: To investigate the use of assistive technology (AT), unmet needs for AT,
      and examine correlates of use of memory aids and cognitive strategies among
      individuals with multiple sclerosis (MS). METHOD: A cross-sectional study of
      1,063 community dwelling adults with MS in Washington State. A self-report survey
      assessed use of AT as well as depression, fatigue, mobility, and other
      demographic and disease related variables. RESULTS: Some 70% of respondents
      reported using memory strategies and 50.7% reported using electronic memory aids.
      The strongest correlate of use of electronic memory aids was endorsement of
      difficulties thinking (OR: 2.09, p < 0.001) though younger age, higher education,
      and report of higher fatigue were also significant. Fatigue (OR: 1.27, p < 0.001)
      and depression (OR: 0.89, p < 0.001) were highly associated with use of memory
      strategies. Subjects who were older, unemployed, more depressed, and have more
      mobility disability were less likely to use memory strategies. CONCLUSIONS: Use
      of AT for memory is widespread and further research should be conducted on
      efficacy of AT. Many individuals who might be presumed to need AT for memory most
      (older, less educated, more disability) are least likely to report use.
      Healthcare providers are urged to ask about memory AT and make appropriate
      referrals.

PMID- 19172477
TI  - Wheelchair accessibility: descriptive survey of curb ramps in an urban area.
AB  - PURPOSE: To determine the extent to which curb ramps in an urban area met a set
      of wheelchair accessibility guidelines. METHOD: For each of 79 intersections in
      an urban area, we collected data about eight accessibility characteristics, based
      on existing guidelines. A total score (0-8) was calculated for each intersection,
      based on the number of criteria met. RESULTS: Of the 79 intersections assessed,
      98.7% had curb ramps. Of the curb ramps, 53.8% provided direct lines of travel
      from the sidewalks to the crosswalks, 93.6% were >or=915 mm in width, 43.6% had
      ramp slopes <or=4.8 degrees (1:12), 57.7% had gutter counter-slopes of <or=2.9
      degrees (1:20), 26.9% had smooth transitions (<or=13 mm) from the curb ramps to
      the gutters, 85.9% were free from irregularities and 100% were free from drainage
      grates. The mean (+/-SD) total score was 5.6 (+/-1.1). Only 2.6% of the
      intersections met all eight criteria. CONCLUSIONS: Although curb ramps were
      usually present at intersections, only a small proportion of them met all of the
      accessibility criteria evaluated. This finding has implications for those
      responsible for installing and maintaining curb ramps and suggests that
      wheelchair users and their caregivers should learn the wheelchair skills needed
      to overcome such accessibility barriers.

PMID- 19172478
TI  - Use of power tilt systems in everyday life.
AB  - PURPOSE: The goal of this study was to monitor and describe the use of power tilt
      systems in everyday life. Additionally, tilt measurements were used to determine
      if participants performed regular pressure relieves. METHODS: Wheelchair
      occupancy and seat position of 16 fulltime power wheelchair users were monitored
      regularly for 1-2 weeks. Daily wheelchair occupancy, typical position, time spent
      at different tilt angles, tilt frequency and pressure relieving tilt (PRT)
      frequency were described. RESULTS: Participants used their tilt systems in many
      different ways, including subjects who typically sat at small (0-14 degrees) tilt
      angles and subjects who typically sat at medium (15-29 degrees) tilt angles. Few
      subjects tilted past 45 degrees. Almost all subjects tilted throughout the day,
      with the median subject performing >3 tilts per hour of wheelchair occupancy.
      Despite the regular use, few subjects performed regular PRTs (median = 0.13/h)
      CONCLUSION: Differences in tilt-use illustrated the variability in function and
      activity among users, as well as the diverse benefits of a tilt system for
      different users. Further study into why subjects did not regularly achieve PRT
      magnitudes would be valuable to inform improved training, education and follow
      up.

PMID- 19172479
TI  - Development of a French-Canadian version of the Life-Space Assessment (LSA-F):
      content validity, reliability and applicability for power mobility device users.
AB  - PURPOSE: To examine the measurement properties of the French-Canadian version of
      the Life-Space Assessment questionnaire (LSA-F) for power mobility device (PMD)
      users. METHODS: Content validity, test-retest reliability of telephone interviews
      (2-week interval) and applicability were examined with PMD users presenting
      neurological, orthopedic or medically complex conditions. Translation/back
      translation from English to French and cultural adaptation was performed and
      pretested with five bilingual users. Test-retest reliability was examined with 40
      French-speaking users, age 50 and over, who had been using a subsidized PMD for 2
      15 months. Audio-taped interviews were coded to judge content validity and
      applicability. RESULTS: Content validity results confirmed equivalent meaning for
      most questions. The test-retest reliability was excellent for the composite score
      (intra-class correlation coefficient = 0.87) and revealed moderate to substantial
      concordance for 18/20 items (k = 0.47-0.73; P(a) > 57.5%). The applicability of
      the LSA-F is satisfactory considering an acceptable burden of assessment, low
      refusal of the telephone interview format (8%; n = 4), reasonable administration
      time (9.2 +/- 3.9 min) and a normally distributed composite score. CONCLUSIONS:
      The LSA-F is a valid measure with regards to its content, stable over a period of
      2 weeks and applicable for a population of middle-aged and older French-Canadian
      speaking adults who use PMDs.

PMID- 19172480
TI  - Design, development and testing of a low-cost electric powered wheelchair for
      India.
AB  - PURPOSE: To design and develop an appropriate, low-cost electric powered
      wheelchair (EPW) for the Indian subcontinent. METHOD: We performed the following
      multi-phase design process: (1) Conceptual design; (2) System design, Prototype I
      fabrication, focus group testing with Indian stakeholders (n = 29); (3) System re
      design, Prototype II fabrication and user trials with US (n = 5) and Indian (n =
      25) subjects. RESULTS: (1) Preliminary investigations revealed that a
      conventional EPW design was infeasible due to the high component cost. Instead,
      we constrained our design to incorporate a single drive motor and manual
      steering, with the option of upgrading to power steering where economically
      feasible. (2) The first prototype was fabricated out of easily available, low
      cost materials. Focus group testing demonstrated feasibility of the design and
      revealed differences between stakeholder groups. (3) Prototype II incorporated
      feedback from the first focus group and a needs assessment. US subjects provided
      valuable design advice prior to the India trials. Indian subjects travelled
      further in the SIMPL-EPW than their own manual wheelchair (MWC). Depending on
      spinal injury level, Indian subjects found the entire (tetraplegia) or outdoor
      portion (paraplegia) of the obstacle course significantly less challenging in the
      SIMPL-EPW compared with their own MWC. CONCLUSIONS: We demonstrated a useful and
      successful multi-phase design approach for developing assistive technology for
      developing regions.

PMID- 19172481
TI  - Effects of vibratory orthosis on balance in idiopathic Parkinson's disease.
AB  - PURPOSE: It was hypothesised that lumbar vibration stimulation applied by a
      vibratory orthosis improves balance in people with Parkinson's disease (PD).
      METHODS: The overall stability index and the percent of elapsed time in different
      zones and quadrants on the platform of Biodex balance system were evaluated.
      General conditions of eyes-open and eyes-close, each with two situations of
      motors On and motors Off of vibratory orthosis were considered. RESULTS: Balance
      in PD patients improved in eyes-open condition rather than eyes-close. The
      balance also improved in eyes-open condition with motors On rather than that in
      motors Off. In eyes-close condition, balance was lesser in motors On than that in
      motors Off situation. The results also suggest that in PD patients, body
      trajectories on the platform of Biodex balance system follow a random-like
      chaotic behaviour. CONCLUSIONS: A new orthosis in rehabilitation of PD patients
      was introduced to enhance balance and decrease risk of fall. It promotes new
      ideas for rehabilitation of similar neurological diseases. The possibility of
      enhancing balance in PD patients in a short-term setting was evaluated. Results
      showed balance enhancement in PD patients in eyes-open condition. However, in
      eyes-close condition, we are not sure of its effectiveness.

PMID- 19172482
TI  - Effects of the CCR5-Delta32 mutation on hepatitis C virus-specific immune
      responses in patients with haemophilia.
AB  - In hepatitis C virus (HCV) infection antiviral T cells express the CC chemokine
      receptor 5 (CCR5). Their recruitment to the liver is an important step in the
      immune response. A 32 base pair deletion in the CCR5 gene leads to reduced
      expression and total loss of CCR5 in CCR5-n32 heterozygous and homozygous
      subjects, respectively. However, the role of this mutation for antiviral immunity
      remains unclear. Here, we analysed proliferation, IFN-gamma and IL-4 secretion
      (ELISpot) induced by the HCV antigens core, NS3, NS4, and NS5a in 21 anti-HCV
      positive haemophiliac patients in relationship to their CCR5 genotypes (CCR5
      wildtype n = 10, CCR5-n32 heterozygous n = 5 and CCR5-n32 homozygous n = 6).
      Furthermore, T cell migration in response to the CCR5 ligands CCL3, -4 and -5 was
      studied. Overall IFN-gamma responses to HCV proteins were only slightly greater
      in CCR5 wild-type patients than in CCR5-n32 carriers (0.6 versus 0.24 SFC/10(4)
      PBMC; p = 0.043). This difference was consistently seen with all tested HCV
      antigens. In contrast, neither T cell migration, nor PBMC proliferation, nor IL-4
      production differed between CCR5 genotypes. Interruption of the CCR5 signalling
      pathway due to CCR5-n32 may potentially result in subtle reduction of HCV
      specific IFN-gamma responses in anti-HCV-positive haemophiliac patients.

PMID- 19172483
TI  - Modulation of steroidogenic enzymes in murine lymphoid organs after immune
      activation.
AB  - To study the effects of immune cell activation by a protein antigen or lymphoid
      tissue derived cytokines on peripheral steroidogenesis activities of 3beta HSD
      and 17beta HSD was measured in lymphoid organs of control and BSA immunized mice
      after 3 weeks treatment. We demonstrated the presence of 3betaHSD and 17betaHSD
      in the lymphoid organs after active immunization. We found elevated serum
      corticosterone after 3 weeks of antigen administration in presence of CFA and a
      higher serum IL-6 level that also alter lymphoid tissue cytokine responses like
      TNF-alpha, IL-12p70, and IL-6, among which IL-12p70 and TNF-alpha down-regulate
      the activity of steroidogenic enzymes in the thymus during an immune response.

PMID- 19172484
TI  - Vibrio vulnificus-induced cell death of human mononuclear cells requires ROS
      dependent activation of p38 and ERK 1/2 MAPKs.
AB  - Vibrio vulnificus is a Gram-negative bacterium that multiplies rapidly in host
      tissue and causes extensive tissue damage. Human peripheral blood mononuclear
      cells (PBMC) were shown to be readily killed by exposure to live V. vulnificus.
      V. vulnificus induced production of intracellular reactive oxygen species (ROS)
      and nitric oxide (NO) in PBMC. Pretreatment of PBMC with diphenyleneiodonium
      chloride (DPI) abolished ROS generation upon exposure to V. vulnificus and
      decreased the bacterial ability to cause cell death. In contrast, pretreatment of
      these cells with inhibitors of inducible nitric oxide synthase (iNOS) blocked V.
      vunificus-induced NO production, but did not significantly alter cell death by V.
      vulnificus. V. vulnificus also triggered phosphorylation of mitogen-activated
      protein kinases (MAPKs), including p38 and ERK1/2 in PBMC. Inactivation of these
      MAPKs by selective inhibitors caused a reduction both in ROS generation and cell
      death induced by V. vulnificus. It was further shown that an inhibitor of ROS
      generation (DPI) blocked V. vulnificus-induced phosphorylation of p38 and ERK1/2
      MAPK. This study demonstrates that V. vulnificus induces death of PBMC via ROS
      dependent activation of p38 MAPK and ERK1/2 MAPK.

PMID- 19172485
TI  - T helper type 2 differentiation is associated with induction of antibacterial
      defense mechanisms in blood lymphocytes of patients with sarcoidosis.
AB  - Whereas sarcoidosis is characterized by an excessive inflammatory immune response
      mainly at the pulmonary site, circulating T lymphocytes poorly respond to antigen
      challenge. It has been suggested, that the extensive local inflammation might be
      triggered by bacterial pathogens. Recently, it has been shown that this
      paradoxically immunological situation likely results from a disequilibrium
      between effector and regulatory T lymphocytes (T(reg)). Here, we apply a DNA
      microarray approach in order to analyze circulating T cells for specific
      dysregulatory events, which should provide detailed insights in the impairment of
      cell-mediated immunity. Gene expression profiles were performed from peripheral
      blood T lymphocytes of untreated patients with pulmonary sarcoidosis (stage I) (n
      = 3) and a control group consisting of healthy donors (n = 3). Circulating T
      lymphocytes in sarcoidosis exhibit a specific gene expression pattern of
      molecules that are primarily involved in immune responses and lymphocyte
      signalling. Compared to controls patients with sarcoidosis display also
      alterations in gene expression of molecules with bacteriolytic and chemotactic
      function. Among others, array analysis resulted in increased transcript levels of
      Th2 immune response, whereas genes coding for molecules involved in Th1
      differentiation are down-regulated. Furthermore, genes encoding proteins
      representing primordial antimicrobial peptides which may mobilise immunocompetent
      T cells and other inflammatory cells are up-regulated. This observation supports
      recent reports suggesting that bacterial antigens play a role in the pathogenesis
      of sarcoidosis. However, the results of our study indicate an unbalanced immune
      response towards Th2 in the peripheral blood of patients with sarcoidosis.

PMID- 19172486
TI  - A comparison between ((3)H)-thymidine incorporation and isothermal
      microcalorimetry for the assessment of antigen-induced lymphocyte proliferation.
AB  - Lymphocyte transformation tests (LTT) are time-consuming radioactive assays used
      in the clinic for the determination of allergic drug reactions and extensively in
      basic immunological research. In the present study we propose an alternative
      method in the monitoring of T-cell responses by isothermal microcalorimetric
      (IMC) measurements of overall cellular heat production as a function of time. For
      mitogen-induced lymphocyte proliferation, we analyzed a concentration dependent
      effect of phytohemaglutinin (PHA) and both tests showed a good correlation. This
      was also the case for specific antigenic stimulation with Varidase(R) or tetanus
      toxoid. On the other hand, antigen-induced lymphocyte proliferation analyzed by
      pre and post influenza vaccine (Inflexal(R) V) samples, showed no such
      correlation. Our study suggests that IMC measurements, despite the advantages of
      simplicity, on-line recording of metabolic activity and no use of radioactivity,
      may be limited to monitoring mitogen-induced lymphocyte proliferation.

PMID- 19172488
TI  - Higher histamine sensitivity in non-atopic subjects by skin prick test may result
      in misdiagnosis of eggplant allergy.
AB  - Eggplant (aubergine; Solanum melongena L.), a member of the nightshade family, is
      widely consumed as a vegetable. A high incidence of allergic reactions to
      eggplant appears to be commonly experienced among Indians, presumably due to its
      high histamine content. Therefore, it appeared interesting to investigate the
      histamine content of different varieties of eggplant (green and purple round;
      green and purple slender long) using raw, cooked, and dialyzed extracts. A
      significant varietal difference in the histamine content of eggplant varieties
      was observed. Highest amount was present in the green round variety (2.41 mg/100
      g fresh weight in raw and 2.07 mg/100 g in cooked extracts). The histamine
      content of other varieties (in mg/100 g raw) is: green slender long (1.80),
      purple slender long (1.35), and purple round (0.89). Histamine is stable to heat
      processing, since only 11-14% loss was observed upon cooking. Skin prick test
      (SPT) on non-atopic subjects (without any history of eggplant allergy) using four
      varieties of raw and cooked eggplant extracts revealed that only subjects with a
      lower threshold for histamine produce positive results equivalent to that seen
      between 10-100 microg/mL histamine dihydrochloride. It can be concluded that the
      amount of histamine present in eggplant does not produce a positive SPT response
      in a majority of non-atopic subjects, and that a positive response in a few
      subjects are likely to be misdiagnosed as eggplant allergy.

PMID- 19172487
TI  - Functional characterization of N297A, a murine surrogate for low-Fc binding anti
      human CD3 antibodies.
AB  - Several low- or non-FcR binding anti-human CD3 monoclonal antibodies have been
      under investigation for the treatment of autoimmune diseases. To model the
      mechanism of action of these anti-human CD3 mAbs in the murine system, an Fc
      modified anti-mouse CD3 antibody (N297A) was generated. N297A exhibited similar
      biological effects as Fc-modified anti-human CD3 antibodies including rapid,
      reversible reduction in peripheral leukocyte numbers, differential modulation of
      activated versus resting T cells, and reduced levels of induced cytokine release
      compared to the non-Fc-modified parent antibody. In an in vivo model of colitis
      induced by adoptive transfer of IL-10-deficient cells, administration of N297A
      significantly reduced body weight loss. As N297A shared many functional
      characteristics of non-FcR binding anti-human CD3 mAbs both in vitro and in vivo,
      it provides a means to model the mechanisms of action of Fc-modified anti-human
      CD3 antibodies in mouse.

PMID- 19172489
TI  - Effect of Bifidobacterium bifidum DSM 20082 cytoplasmic fraction on human immune
      cells.
AB  - The objective of the present study was to determine the effect of the soluble
      cytoplasmic fraction from Bifidobacterium bifidum DSM 20082 (Bb) lysate on
      peripheral blood T cells. In peripheral blood mononuclear cells of healthy
      subjects, cytotoxic activity, proliferation, apoptosis, and up-regulation of CD8
      or CD4 molecules in T cells were examined. When peripheral blood mononuclear
      cells were stimulated with Bb lysate, the main effect was observed in CD8+ cells
      as a significant increase of CD8 molecules in a dose-dependent manner, and this
      behavior was observed at 24, 48, and 72 h after stimulation; in contrast,
      stimulation with Bb lysate showed no effect on the up-regulation of CD4 molecules
      in T helper cells. Further Bb lysate did not induce proliferation activity in
      either CD8+ or CD4+ cells. Bb lysate induced activation of CD8+ cytotoxic
      activity against autologous monocytes. Around 80% of the cells stimulated with Bb
      lysate were positive to peanut agglutinin (PNA), suggesting that the stimulated
      CD8+ cells corresponded to activated/effector cellular populations. When
      apoptosis was determined, there were no differences between stimulated and non
      stimulated cells. Our results indicate that Bb lysate is able to increase
      cytotoxic activity of peripheral CD8+ cells, without affecting lymphocyte
      survival.

PMID- 19172490
TI  - Science in the Making: Right Hand, Left Hand. I: A BBC television programme
      broadcast in 1953.
AB  - In August 1953, the BBC broadcast a television science programme entitled Science
      in the Making: Right Hand, Left Hand. The programme was broadcast live, being
      presented by Dr Jacob Bronowski in collaboration with Dr Kenneth Smith, and
      produced by George Noordhof. It not only presented a popular account of current
      ideas about right- and left-handedness, by using a group of celebrities (and a
      chimpanzee) in the studio, but also asked viewers to complete a brief
      questionnaire on handedness, which was printed in the Radio Times. Recently 6,336
      of the returned questionnaires, which were said to have been analysed by Sir
      Cyril Burt and a colleague, were found in the archive of the Psychology
      Department of University College London. The present paper describes what we have
      discovered about the programme from various sources, including the producer and
      the son of Dr Kenneth Smith, and also presents basic descriptions of the
      postcards and the response to the programme. In two subsequent papers we will
      describe our analysis of the data from the postcards, which represents an
      unusual, large-scale survey of handedness in the mid-twentieth century.

PMID- 19172491
TI  - Imitation of lateralised body movements: doing it the hard way.
AB  - Two experiments examined imitation of lateralised body movement sequences
      presented at six viewing angles (0 degrees , 60 degrees , 120 degrees , 180
      degrees , 240 degrees , and 300 degrees rotation relative to the participant's
      body). Experiment 1 found that, when participants were instructed simply to "do
      what the model does", at all viewing angles they produced more actions using the
      same side of the body as the model (anatomical matches), than actions using the
      opposite side (anatomical non-matches). In Experiment 2 participants were
      instructed to produce either anatomical matches or anatomical non-matches of
      observed actions. When the model was viewed from behind (0 degrees ), the
      anatomically matching group were more accurate than the anatomically non-matching
      group, but the non-matching group was superior when the model faced the
      participant (180 degrees and 240 degrees ). No reliable differences were observed
      between groups at 60 degrees , 120 degrees , and 300 degrees . In combination,
      the results of Experiments 1 and 2 suggest that, when they are confronting a
      model, people choose to imitate the hard way; they attempt to match observed
      actions anatomically, in spite of the fact that anatomical matching is more
      subject to error than anatomical non-matching.

PMID- 19172492
TI  - Idiotype vaccination for lymphoma: moving towards optimisation.

PMID- 19172493
TI  - Outpatient or inpatient stem cell transplantation: patria est ubicunque est bene?

PMID- 19172494
TI  - Managing hematopoietic stem-cell transplant resources: the case for outpatient
      transplantation.

PMID- 19172495
TI  - Circulating endothelial cells in chronic lymphocytic leukemia: more evidence of
      disturbed angiogenesis.

PMID- 19172496
TI  - Transcriptional profiling of chronic lymphocytic leukemia: is there still more to
      learn?

PMID- 19172497
TI  - Treatment of elderly adults with acute promyelocytic leukemia: put the pedal to
      metal.

PMID- 19172498
TI  - Efficacy and safety of micafungin, an echinocandin antifungal agent, on invasive
      fungal infections in patients with hematological disorders.
AB  - The study was conducted as a prospective multicenter trial to evaluate the
      efficacy and safety of micafungin in patients with invasive fungal infections
      (IFIs) in hematological disorders. A total of 277 patients was registered, and
      197 were assessed for clinical efficacy. The mean dosage and duration of
      micafungin were 170.7 mg/day and 22.0 days, respectively. The efficacy rates were
      87.5% (7/8) for patients with candidiasis, 44.7% (17/38) for probable IFIs, 61.9%
      (39/63) for possible IFIs and 80.7% (71/88) for those who failed to respond to
      antibacterials. In patients with febrile neutropenia (below 500 microL), despite
      broad-spectrum antibacterial treatment over 2 days, 86.3% (44/51) of patients had
      a favourable response to micafungin. The incidence of adverse events related to
      micafungin was 14.1% (39/277), but most of them were mild and reversible. These
      data indicate the usefulness of micafungin as a novel therapeutic drug for both
      empirical and targeted therapy for IFIs.

PMID- 19172500
TI  - Substance use disorders among personality disordered patients admitted for day
      hospital treatment. Implications for service developments.
AB  - Personality disorders (PD) and substance use disorders (SUD) are highly comorbid
      conditions. However, their treatment services are often separated. The aims of
      this study was to investigate how extensive this separation was prior to a
      Norwegian health reform (2004) that promoted integration, and to discuss clinical
      challenges for an integrated treatment of PD and SUD. All patients with a
      diagnosis of PD (n=1783) admitted to 10 day hospital treatment programs (1993
      2003) were examined. Diagnoses were assessed by Mini International
      Neuropsychiatric Interview and Structured Clinical Interview for DSM-IV
      interviews. Socio-demographic data, psychosocial functioning (Global Assessment
      of Functioning Scale), symptom distress (Symptom Check List-90-Revised),
      interpersonal problems (Circumplex of Interpersonal Problems) and treatment
      course were recorded. The majority of patients were females (72%) and the
      prevalence of SUD was low (14%). SUD occurred among all PD categories. Patients
      with borderline PD were over-represented and patients with cluster C disorders
      were under-represented in the SUD sample. The SUD sample contained more men and
      it was associated with more previous violence against self and others. The
      reported violence was partly explained by gender (males) and diagnoses
      (borderline and SUD). PD patients with SUD also displayed more aggression during
      treatment and dropped out more frequently. The findings demonstrate that the
      female dominated specialized psychiatric treatment services for PD to a large
      extent had excluded PD patients who also had SUD. The reasons are probably
      related to the surplus problems that characterized the SUD sample and gender
      issues. Implications for the development of the PD and SUD services with respect
      to an integrated treatment for these comorbid conditions are discussed.

PMID- 19172501
TI  - Current trends in psychiatry care in Finland with special focus on private
      practice psychiatry and psychotherapy.
AB  - Several previous reforms decentralized Finnish psychiatric services to a great
      extent. The Ministry of Social Affairs and Health is outlining a proposal for
      Health Care Law, which makes an effort to centralize and reorganize healthcare.
      It is not yet possible to see what this will mean for the psychiatric services.
      In general, the health status of the Finnish population has improved. Although
      rates of suicides have declined considerably, rates of alcohol-related deaths
      have risen. Moreover, disability related to major depression has increased
      drastically, which has lead to a nationwide project called MASTO, which has the
      aim to improve early detection and treatment of depression. The Ministry of
      Social Affairs and Health set up a work group, MIND 2009, to draft local working
      models for mental health and addiction services. To study the significance of
      psychotherapy in a private practice psychiatric context, the Finnish Psychiatric
      Association conducted a survey amongst its members. Most psychiatrists in private
      practice conduct psychotherapy.

PMID- 19172502
TI  - Interview with Professor Egil W. Martinsen by Toril Dammen.

PMID- 19172503
TI  - Macular dysfunction and morphology in spinocerebellar ataxia type 7 (SCA 7).
AB  - PURPOSE: To characterize the clinical phenotype regarding retinal function and
      macular appearance in patients with spinocerebellar ataxia type 7 (SCA 7), with
      an emphasis on electrophysiological findings. METHODS: Three patients from two
      Swedish families were given an ophthalmological examination including visual
      acuity, fundus inspection, Farnsworth's color vision test, Goldmann perimetry,
      full-field electroretinography (full-field ERG), multifocal electroretinography
      (mfERG) and optical coherence tomography (OCT). DNA was analyzed with polymerase
      chain reaction for CAG trinucleotide expansion repeats in the SCA 7 gene.
      RESULTS: Molecular analysis demonstrated abnormally expanded CAG repeats in the
      gene for SCA 7, which encodes the protein ataxin-7, thus confirming the diagnosis
      SCA 7. In the oldest patient very discreet pigmentary changes in the maculae were
      found, but with that exception the patients had a normal ophthalmoscopic fundus
      appearance and OCT demonstrated only minor changes. MfERG indicated predominantly
      central involvement, especially in the early disease stages, which in pace with
      disease progression extended from the center to the more peripheral areas. Full
      field ERG in the oldest patient demonstrated bilaterally distinctly prolonged 30
      Hz flicker implicit time, verifying widespread cone photoreceptor degeneration.
      CONCLUSIONS: The patients with genetically confirmed SCA 7 presented an early
      macular dysfunction, preceding any signs of abnormalities in fundus appearance.
      According to the electrophysiological findings the primary dysfunction involves
      the cone photoreceptors in the foveal region, however in an older patient
      involvement of cone photoreceptors throughout the retina was verified. This is in
      accordance with the theory that ataxin-7 interacts with CRX transcription, since
      it is known that mutations in the CRX gene cause cone-rod dystrophy.

PMID- 19172504
TI  - Duane retraction syndrome, nystagmus, retinal pigment epitheliopathy and
      epiretinal membrane with micro- and pachygyria, developmental delay, hearing loss
      and craniopharyngioma.
AB  - PURPOSE: To report the association of Duane syndrome with nystagmus and a
      patterned hyperpigmentation of the retinal pigment epithelium, developmental
      delay, micro- and pachygyria and craniopharyngioma. CASE REPORT: We describe a 12
      year old girl with developmental delay, hearing loss, cortical micro- and
      pachygyria, and a cystic craniopharyngioma; her ocular features include
      unilateral Duane syndrome, monocular nystagmus under binocular conditions, and a
      patterned hyperpigmentation of the retinal pigment epithelium. Her mother had
      similar retinal pigment epithelial abnormalities. CONCLUSIONS: The combination of
      two neuronal migrational disorders, the unusual retinal pigment epithelial
      abnormalities in the proband and her mother, and evidence that each feature may
      be genetic and are suggestive of a genetic basis for this constellation of
      features.

PMID- 19172505
TI  - Lack of association between optineurin gene variants T34T, E50K, M98K,
      691_692insAG and R545Q and primary open angle glaucoma in Brazilian patients.
AB  - PURPOSE: To verify the frequencies of T34T, E50K, M98K, 691_692insAG, and R545Q
      variants in the optineurin (OPTN) gene in Brazilian subjects with primary open
      angle glaucoma (POAG) and controls. PATIENTS AND METHODS: Ninety-nine patients
      with POAG and 100 normal controls were enrolled in this study. The frequency of
      alterations in the OPTN gene was analyzed by direct sequencing and enzymatic
      digestion of PCR products. RESULTS: None of the five alterations evaluated was
      significantly associated with POAG when compared to controls. However, the T34T
      silent change was present in greater frequency in POAG patients (37.37% vs.
      23.00% in controls), while the R545Q change was more prevalent in controls
      (23.00% vs. 10.10% in POAG). The M98K and 691_692insAG presented with low
      frequencies in POAG patients (1.01% and 2.02%, respectively) and controls (2.00%
      and 2.00%, respectively). The E50K substitution was not observed. CONCLUSION: Our
      data show no association between the five evaluated variants and POAG in the
      Brazilian population.

PMID- 19172506
TI  - Uncommon associations with ataxia-telangiectasia: vitiligo and optic disc drusen.
AB  - Ataxia-telangiectasia (A-T) is an autosomal recessive condition presented by
      progressive cerebellar ataxia, oculocutaneous telangiectasia, humoral and
      cellular immunodeficiencies and a predisposition to malignancy. We report on a 13
      years old male patient with the diagnosis of A-T associated with uncommon
      clinical features; optic disc drusen and vitiligo. To our knowledge, this is the
      first report of A-T associated with these findings.

PMID- 19172507
TI  - Phenotypic overlap of familial exudative vitreoretinopathy (FEVR) with persistent
      fetal vasculature (PFV) caused by FZD4 mutations in two distinct pedigrees.
AB  - PURPOSE: To describe a severe familial exudative vitreoretinopathy (FEVR)
      phenotype seen in infancy that resembles persistent fetal vasculature (PFV)
      caused by mutations in the FZD4 gene in two pedigrees with high intrafamilial
      variability. METHODS: Three infants presented with features compatible with
      bilateral PFV. Eye examinations from the affected children and their relatives
      were reviewed retrospectively (follow-up:18 months-9 years). Mutation screening
      was performed using direct sequencing of the FZD4, LRP5 and NDP genes. RESULTS:
      Bilateral retinal folds extending from the optic nerve to the inferotemporal
      aspect of the lens mimicing PFV were observed in two of the three affected
      children before the age of two months. The third child was examined at birth, and
      the avascular peripheral retina treated with diode laser within one week of age,
      with subsequent arrest of the disease process. A FZD4 mutation, M493_W494del, was
      identified in one affected child in pedigree 1, and a novel missense mutation,
      I114T, was detected in 2 affected children in pedigree 2; while no mutations were
      found in NDP or LRP5 genes in the 3 affected children. In both pedigrees, at
      least one affected relative was asymptomatic and failed to show the
      characteristic avascular changes of FEVR. CONCLUSIONS: The clinical features in
      the three children and their relatives with a documented FZD4 mutation support
      the previous reports of a high degree of intrafamilial and interfamilial
      variability in FEVR. In extreme cases with very early onset, the development of a
      retinal fold can mimic PFV, a non-hereditary condition with rare exception.

PMID- 19172508
TI  - The effect of therapy refusal against medical advice in retinoblastoma patients
      in a setting where treatment delays are common.
AB  - BACKGROUND: Patients who refuse therapy against medical advice may be at risk of
      adverse health outcomes. We analyzed the impact of therapy refusal and its effect
      on the survival of retinoblastoma patients. PATIENTS AND METHODS: 165 consecutive
      untreated retinoblastoma patients admitted to the CM-Hospital, between 1993-2000
      were evaluated retrospectively. Survival outcomes and its association with delays
      and tumor staging were analyzed using Kaplan-Meier and Cox-Regression. RESULTS:
      Of the 165 cases, 78 cases (47,3%) were assigned to the "No-Refusal-Group"; 52
      cases (31,5%) to "Temporary-Refusal-Group," 30 cases (18,2%) to "Definite-Refusal
      Group." Survival rates of patients who temporarily refused were significantly
      lower than those who did not refuse the therapy (p < 0.05). Progression of tumor
      stage was highly associated with temporary-refusal (p < 0.0005). In the Cox
      Regression model, clinical staging of tumor was highly associated, whereas
      admission delay and treatment delay were slightly associated with the overall
      survival (p < 0.05, adjusted-hazard-ratio 6.321, 1.031,1.025, respectively). The
      clinical staging is the strongest variable associated with patient survival
      outcome. Delay >or= 6 months between first sign and admission is highly
      associated with tumor progression (p < 0.0005). CONCLUSIONS: First, the high
      level of therapy refusal in a developing country like Indonesia has an adverse
      effect on the survival outcome of retinoblastoma patients. Second, the change of
      the tumor stage from intraocular to extraocular is the most adverse predictive
      factor for survival. Third, the advanced stage of the tumor is caused by long
      delay to admission. In a developing country the parents of many young patients
      refuse to accept the recommended therapy and therefore the tumor may reach a
      critical stage for the prognosis.

PMID- 19172509
TI  - Congenital alacrima in a patient with blepharophimosis syndrome.
AB  - PURPOSE: To report a case of congenital alacrima in a patient with
      Blepharophimosis Syndrome (BPES). METHODS: Case report of a 9-month-old female
      who presented with severe dry eyes. Further investigation revealed bilateral
      absence of lacrimal glands confirmed by CT. This unique case and its management
      are discussed. RESULTS: Conservative management with artificial tears and
      ointment did not treat the ocular surface dryness. A combination of aggressive
      lubrication with surgical occlusion of the lower lid punctums was required to
      improve the corneal surface. CONCLUSION: BPES can be associated with many
      ophthalmic and facial abnormalities. Review of the pubmed literature, reveals
      this is the first reported case of alacrima and BPES. Patient with alacrima have
      severe ocular surface dryness, which requires aggressive and life long
      lubrication and tear supplementation.

PMID- 19172510
TI  - Published international classification of retinoblastoma (ICRB) definitions
      contain inconsistencies--an analysis of impact.
AB  - PURPOSE: To determine the impact of subtle differences (most notably in their
      classification of group E eyes) in two published versions of the ICRB
      (Philadelphia and the Children's Hospital Los Angeles). METHODS: Analysis of a
      series of 96 eyes with intra-ocular retinoblastoma. RESULTS: The disparate
      criteria of the 2 published ICRB schemas affected group assignment of 5.2% of the
      eyes (25% of the group E eyes). CONCLUSION: Discrepancies need to be reconciled
      to ensure accurate and uniform application of the ICRB.

PMID- 19172511
TI  - Triple A or Allgrove syndrome. A case report with ophthalmic abnormalities and a
      novel mutation in the AAAS gene.
AB  - PURPOSE: Triple A syndrome is a rare autosomal recessive disease characterized by
      achalasia, alacrima, adrenocorticotrophic hormone resistant adrenal failure and
      some neurologic abnormalities. We report a nine year old patient with alacrima,
      optic atrophy and achalasia with mutation in the AAAS gene. METHODS: PCR
      amplification of the complete coding sequence as well as the exon-intron
      junctions of AAAS gene was performed in DNA from the patient and his parents.
      RESULTS: AAAS gene analysis demonstrated a homozygous A to G mutation at
      nucleotide position 122 in exon 1 in DNA from the patient. CONCLUSIONS: The novel
      mutation described confirms the diagnosis.

PMID- 19172512
TI  - Cystoid macular edema in a patient with chronic progressive external
      ophthalmoplegia with mitochondrial myopathy.
AB  - PURPOSE: To report the findings of cystoid macular edema in a patient with
      chronic progressive external ophthalmoplegia and other systemic features of
      mitochondrial myopathy. DESIGN: Observational case report. METHODS: Retrospective
      review of the ophthalmic examination and genetic studies of a patient with
      chronic progressive ophthalmoplegia. RESULTS: Fundus photos, retinal optical
      coherence tomography, and fluorescein angiography were significant for findings
      consistent with bilateral cystoid macular edema, which were found to have
      resolved after 18 months without treatment. The medical examination supported the
      diagnosis of chronic progressive external ophthalmoplegia. Fundus photos, retinal
      optical coherence tomography, and fluorescein angiography were significant for
      findings consistent with cystoid macular edema. CONCLUSIONS: This case
      demonstrates the occurrence CME in a patient with CPEO and additional systemic
      features.

PMID- 19172513
TI  - LCA5, a rare genetic cause of leber congenital amaurosis in Koreans.
AB  - PURPOSE: Leber congenital amaurosis (LCA), the most severe form of inherited
      retinal dystrophy, is a genetically heterogenous disorder and more than nine
      genes only account for about half of LCA cases. Recently, LCA5 was identified as
      a rare genetic cause of LCA. Here, we analyzed the LCA5 gene in 14 LCA patients
      with no mutation identified in any other known LCA genes and 3 patients with one
      unclassified missense variant in RPGRIP1. METHODS: We analyzed all exons and
      flanking regions of the LCA5 gene using direct sequencing. We included 170
      control subjects in this study to screen novel sequence variant and analyzed the
      functional effect of a missense variant using in-silico prediction. RESULTS: No
      pathogenic mutation in LCA5 was found in our seventeen patients including 3
      patients with one unclassified missense variant in RPGRIP1. We identified one
      novel missense variant, c.1642C>T (p.Pro548Ser), in exon 9. We considered it
      benign because it was found in control subjects and predicted not to be harmful
      to protein function on in-silico prediction. We identified another intronic
      variant, which has been confirmed to be benign through mRNA analysis.
      CONCLUSIONS: This result shows that mutation in LCA5 is likely to be a rare
      genetic cause in Koreans and suggests that further investigation to identify
      other causative genes is necessary in Koreans.

PMID- 19172514
TI  - Evaluation of the Impact-R for monitoring the platelet storage lesion.
AB  - The aim of this study was to evaluate the Impact-R test for measuring changes in
      platelet function in stored platelet concentrates. Platelet function was measured
      within samples (reconstituted with red cells) taken from apheresis concentrates
      (n = 20) and buffy coat concentrates (n = 20) stored for up to 7 days. The final
      mean platelet counts and haematocrits in apheresis concentrates were 319 x
      10(9)/l and 56.2%, and in buffy coat concentrates they were 296 x 10(9)/l and
      54.6%, respectively. The surface coverage (a measure of adhesion) decreased
      significantly during storage of PCs from 11.6 +/- 4 and 8.5 +/- 3.8% on day 1 to
      7.4 +/- 3.4 and 5.9 +/- 3% on day 7 in apheresis and buffy coat concentrates,
      respectively. Buffy coat concentrates exhibited a significantly lower surface
      coverage than apheresis concentrates on day 1 of testing. The average size (a
      measure of aggregation) also decreased significantly during storage from 26.9 +/-
      3.7 microm(2) and 24.1 +/- 3.1 microm(2) on day 1 to 21.8 +/- 3 microm(2) and
      20.8 +/- 2.2 microm(2) on day 7 in apheresis and buffy coat concentrates,
      respectively. However, in contrast to the surface coverage, no significant
      difference in the average size between the two types of concentrate was observed.
      In conclusion, both platelet adhesion and aggregation measured by the Impact-R
      device decline significantly during the storage of platelet concentrates. The
      Impact-R is a simple device to perform rapid test which may be useful for the
      assessment of platelet function within platelet concentrates.

PMID- 19172515
TI  - The effect of ex vivo anticoagulants on whole blood platelet aggregation.
AB  - Pre- and intraoperative platelet function monitoring is increasingly recommended
      in order to detect risk factors for bleeding and to target coagulation
      management. The ideal anticoagulant for accurate platelet aggregometry remains
      controversial. The aim of this experimental trial was to compare platelet
      aggregability in whole blood stored in citrate, heparin and direct thrombin
      inhibitors. Whole blood was drawn from 11 healthy adult volunteers who had not
      taken any medication in the previous 14 days. Blood was stored in trisodium
      citrate, unfractionated heparin, melagatran, lepirudin and argatroban. Platelet
      aggregation was performed using the impedance aggregometer Multiplate (Dynabyte,
      Munich, Germany) with adenosine diphosphate (ADP), thrombin receptor activating
      peptide (TRAP), collagen, arachidonic acid and ristocetin as agonists. Samples
      were analysed immediately after blood sampling (baseline), as well as 30 and 120
      min afterwards. At baseline there were no significant differences in
      aggregability between samples containing direct thrombin inhibitors and heparin.
      In contrast, aggregation in response to all agonists except for ristocetin was
      significantly impaired in citrated blood. During storage the response to
      arachidonic acid and collagen was maintained by direct thrombin inhibitors and
      heparin, whereas ADP-, TRAP- and ristocetin-induced aggregation varied
      considerably over time in all ex vivo anticoagulants tested. Pre-analytical
      procedures should be standardized because storage duration and anticoagulants
      significantly affect platelet aggregability in whole blood. For point-of-care
      monitoring with immediate analysis after blood withdrawal all tested direct
      thrombin inhibitors as well as unfractionated heparin can be used as
      anticoagulants whereas citrate is not recommended.

PMID- 19172516
TI  - Glanzmann's thrombasthenia in North Indians: sub classification and carrier
      detection by flow cytometry.
AB  - Thirty-three patients of Glanzmann's thrombasthenia (GT) and their families were
      assessed for the expression of alphaIIbbeta3 on platelet surface, by flow
      cytometry, to determine the common subtypes in North Indians as well as to assess
      the carrier status in family members of GT patients. GT was diagnosed in patients
      with bleeding manifestations accompanied by absent/reduced platelet aggregation,
      secondary to adenosine-di-phosphate, adrenaline, arachidonic acid and collagen.
      Based on alphaIIbbeta3 levels, 21 patients (64%) were classified as type I (as
      alphaIIbbeta3 was absent), 4 patients (12%) as type II and 8 patients (24%) as
      type III. Eight out of 20 fathers, 10 out of 20 mothers and 20 out of 31 siblings
      were found to have reduced alphaIIbbeta3 levels. Reduced alphaIIbbeta3 expression
      was seen in 63% of parents and 65% of siblings. It is possible that low
      alphaIIbbeta3 levels in family members may reflect their carrier status. It is
      postulated that flow cytometry estimation of alphaIIbbeta3 in parents/siblings
      may detect carrier status in GT. It is also revealed that type I GT is the
      commonest subtype in North Indians.

PMID- 19172517
TI  - The effects of pitavastatin, eicosapentaenoic acid and combined therapy on
      platelet-derived microparticles and adiponectin in hyperlipidemic, diabetic
      patients.
AB  - Platelet-derived microparticles (PDMP) play an important role in the pathogenesis
      of diabetic vasculopathy, and statins or eicosapentaenoic acid (EPA) have been
      shown to have a beneficial effect on atherosclerosis in hyperlipidemic patients.
      However, the influence of EPA and statins on PDMP and adiponectin in
      atherosclerosis is poorly understood. We investigated the effect of pitavastatin
      and EPA on circulating levels of PDMP and adiponectin in hyperlipidemic patients
      with type II diabetes. A total of 191 hyperlipidemic patients with type II
      diabetes were divided into three groups: group A received pitavastatin 2 mg once
      daily (n = 64), group B received EPA 1800 mg daily (n = 55) and group C received
      both drugs (n = 72). PDMP and adiponectin were measured by ELISA at baseline and
      after 3 and 6 months of drug treatment. Thirty normolipidemic patients were
      recruited as healthy controls. PDMP levels prior to treatment in hyperlipidemic
      patients with diabetes were higher than levels in healthy controls (10.4 +/- 1.9
      vs. 3.1 +/- 0.4 U/ml, p < 0.0001), and adiponectin levels were lower than
      controls (3.20 +/- 0.49 vs. 5.98 +/- 0.42 microg/ml, p < 0.0001). PDMP decreased
      significantly in group B (before vs. 6M, 10.6 +/- 2.0 vs. 8.0 +/- 1.7 U/ml, p <
      0.01), but not in group A (before vs. 6M, 9.4 +/- 1.9 vs. 9.6 +/- 1.7 U/ml, not
      significant). In contrast, group A exhibited a significant increase in
      adiponectin levels after treatment (before vs. 6M, 3.29 +/- 0.51 vs. 4.16 +/-
      0.60 microg/ml, p < 0.001). Furthermore, group C exhibited significant
      improvement in both PDMP and adiponectin levels after treatment (PDMP, before vs.
      6M, 11.2 +/- 2.0 vs. 4.5 +/- 2.7 U/ml, p < 0.001; adiponectin, before vs. 6M,
      3.24 +/- 0.41 vs. 4.02 +/- 0.70 microg/ml, p < 0.001). Reductions of PDMP in
      combined therapy were significantly greater than those observed with EPA alone (p
      < 0.05 by ANOVA). In addition, soluble CD40 ligand exhibited almost the same
      change as PDMP in all therapy groups. These results suggest that pitavastatin
      possesses an adiponectin-dependent antiatherosclerotic effect, and this drug is
      able to enhance the anti-platelet effect of EPA. The combination therapy of
      pitavastatin and EPA may be beneficial for the prevention of vascular
      complication in hyperlipidemic patients with type II diabetes.

PMID- 19172518
TI  - Increased mean platelet volume in patients with slow coronary flow.
AB  - Mean platelet volume (MPV) is an indicator of platelet activation, a central
      process in the pathophysiology of coronary heart disease (CAD). The importance of
      slow coronary flow (SCF) phenomenon results from its association with angina
      pectoris, acute myocardial infarction, hypertension and sudden cardiac death. The
      aim of this study is to evaluate the values of MPV in patients with SCF. MPV was
      measured in 84 consecutive patients with SCF and 88 patients with CAD and 84
      control subjects. The association between thrombolysis in myocardial infarction
      (TIMI) frame count (TFC) and MPV level and other clinical and laboratory
      parameters were evaluated. There were no statistically significant differences in
      MPV between SCF group and CAD group. MPV was significantly higher in patients in
      the both SCF and CAD groups, compared with control group. The TFC for all the
      epicardial coronary arteries and the mean TFC were significantly higher in the
      SCF group than the both CAD group and control group. The mean TFC was positively
      and moderately correlated with MPV in the whole study population. To determine
      the independent predictors of mean TFC, a stepwise linear regression analysis was
      performed by including the parameters that were correlated with the mean TFC in
      the bivariate analysis. MPV level was the only independent predictor of the mean
      TFC (b = 0.312, p < 0.001). These findings have shown that MPV level is
      significantly associated with coronary blood flow and that elevated MPV level
      might be an independent predictor for the presence of SCF. We believe that
      further studies are needed to clarify the role of MPV in SCF complicated CAD,
      especially in relation to angiographic and clinical parameters, before we
      conclude that MPV to be used as a follow-up marker during the management of
      relevant patients.

PMID- 19172519
TI  - Platelet alpha- and beta-secretase activities: A preliminary study in normal
      human subjects.
AB  - beta-amyloid (Abeta) arises from an amyloid precursor protein (APP) via beta- and
      gamma-secretase proteolysis. Platelets are the primary depot of APP in the
      circulation and may be a source of cerebral Abeta. We measured the platelet
      activities of alpha- and beta-secretases in normal individuals. Platelet alpha-
      and beta-secretase activities were linear with respect to incubation time and
      quantity of platelet extract included in the assays. beta-secretase activity,
      calculated relative to platelet count (PC) and platelet protein (PP), varied
      between individuals 3.5-fold and 4.6-fold, respectively. Meanwhile, alpha
      secretase varied 3.75-fold and 5.8-fold. beta-secretase/alpha-secretase ratios
      varied 4.1-fold (PC) or 10.5-fold (PP). beta-secretase correlated with age (r =
      0.779, p < 0.02, PP) and mean platelet volume (MPV) (r = 0.702, p < 0.05, PC).
      alpha-secretase correlated negatively with high-density lipoprotein (HDL) (-0.76,
      p < 0.01, PP). beta-secretase/alpha-secretase ratios correlated with MPV (r =
      0.67, p < 0.05, PC) and HDL (r = 0.77, p < 0.02, PP). These data could indicate
      that platelet secretase activity is related to aging, platelet size and plasma
      lipoprotein levels. Clearly, however, this is a preliminary study involving a
      limited number of individuals and further, more detailed, investigations are
      required to establish that such relationships are valid.

PMID- 19172520
TI  - Novel mutations in GP IIb gene in Glanzmann's thrombasthenia from India.
AB  - The integrin GPIIb-IIIa plays an important role in platelet activation and plug
      formation. Quantitative and qualitative dysfunction in this receptor causes
      Glanzmann's thrombasthenia (GT) and leads to a bleeding tendency. Mutations in
      the GPIIb or GPIIIa gene are known to be responsible for the inherited form of
      this disease, which is characterized by mucocutaneous bleeding and other
      clinically severe bleeding manifestations. GT is an autosomal inherited platelet
      function. Mutations in the GPIIIa gene but not GPIIb gene in GT patients from
      Western India have been studied. Hence, this study was designed and included for
      the first time two mutation detection strategies: single strand conformation
      polymorphism and conformation sensitive gel electrophoresis followed by
      sequencing. Patients diagnosed as GT in our laboratory were screened for
      mutations. We report 12 mutations in 13 patients, of which 11 are novel
      mutations. Six mutations were missense, four were deletions and two were splice
      junction mutations. The study thus identifies novel mutations in the GPIIb gene
      in patients from Western India, implicating the importance of certain amino acids
      in structure-function correlations as well as enabling prenatal diagnosis in
      these families.

PMID- 19172521
TI  - Platelet structural pathology in a patient with the X-linked GATA-1, R216Q
      mutation.
AB  - The ultrastructural pathology of GATA-1, V205M and G208S macrothrombocytes was
      discussed in earlier investigations. This study has used the same technology to
      evaluate macrothrombocytes from a patient with the GATA-1, R216Q mutation. Some
      of the pathological features observed in macrothrombocytes from patients with the
      V205M and G208S variations including hypo- and agranular platelets, tubular
      inclusions and platelets within platelets, as well as platelets within platelets
      within platelets were identified. However, tubular membrane sheets in
      megakaryocytes and platelets of the V205M and G208S types and large groups of
      platelets attached to platelets to form megathrombocytes were not observed. The
      unique pathology of the megathrombocytes from this patient was the near absence
      of dense bodies in his giant cells. Storage Pool Deficiency, together with large
      platelets, defective adhesion and aggregation of his macrocytes under shear
      stress to vWF and collagen and defective clot retraction may contribute to the
      pathogenesis of his bleeding disorder.

PMID- 19172522
TI  - Anti-platelet drugs and outcome in severe infection: clinical impact and
      underlying mechanisms.
AB  - Platelet activation contributes to microvascular thrombosis and organ failure in
      systemic inflammation. We tested the hypothesis whether anti-platelet drugs might
      favourably affect outcome in patients at risk for organ failure as well as in a
      mouse model of endotoxin shock. Two hundred twenty-four consecutive patients who
      were admitted for community acquired pneumonia over a time period of 5 years to a
      University Hospital were enrolled; about 20% of whom received anti-platelet drugs
      (acetylsalicylic acid, thienopyridines) for secondary prevention of
      cardiovascular disease. Patients with anti-platelet drugs were about 12 years old
      but did not differ in SOFA score and routine laboratory parameters at admission.
      Logistic regression and 2 x 2 table analysis in age-matched subgroups indicated
      that anti-platelet drugs may reduce the need of intensive care treatment (odds
      ratio (OR) 0.32 [95% confidential interval: 0.10-1.00] and 0.19 [0.04-0.87],
      respectively). In age-matched subgroups, the use of anti-platelet drugs was also
      associated with a shorter stay in hospital (13.9 +/- 6.2 vs. 18.2 +/- 10.2 days;
      p < 0.02). In the animal model Balb/c mice were pre-treated with clopidogrel
      (added to drinking water) for 4 days prior to intraperitoneal (i.p.)
      administration of endotoxin (lipopolsaccharide (LPS) from Escherichia coli
      0111:B4). Within the first 48 hours after LPS there were no differences between
      clopidogrel and control animals (n = 26 each) in macro-haemodynamics. However,
      clopidogrel abolished the LPS-induced drop in platelet count and reduced fibrin
      deposition in lung tissue. Using DNA microarray technology, we could show that
      clopidogrel suppressed endotoxin-induced up-regulation of inflammation-relevant
      genes, including arachidonate-5-lipoxygenase activating protein and leukotriene
      B4 receptor 1. According to our data a possible benefit of anti-platelet drugs in
      patients on risk for systemic inflammation and organ failure should be tested in
      a prospective trial.

PMID- 19172523
TI  - Lifestyle modification decreases the mean platelet volume in prehypertensive
      patients.
AB  - Mean platelet volume (MPV) is an indicator of platelet activation. The present
      study was designed to investigate platelet function by measuring MPV, platelet
      count (PLC) and platelet mass (PLM) in prehypertensive (PHT) subjects.
      Additionally, we also evaluated the effects of lifestyle modification on platelet
      functions by measuring MPV, PLC and PLM. We selected 36 newly diagnosed PHT
      patients and 21 control subjects (BP < 120/80 mmHg) matched for age and sex.
      Lifestyle modifications (weight loss, reduced sodium intake, increased physical
      activity, limited alcohol consumption and the Dietary Approaches to Stop
      Hypertension (DASH) diet) were recommended to PHT individuals for 20 weeks. At
      entry into the study, although PLM and PLC values were similar between study
      groups, MPV values were significantly higher in the PHT group than in the control
      group (respectively, 10.41 +/- 0.93 fl vs. 9.56 +/- 1.04 fl, p < 0.01).
      Additionally, MPV was positively correlated with the systolic blood pressure
      (BP), body mass index (BMI) and insulin resistance (IR) in the PHT group (r:
      0.41; p < 0.02, r: 0.37; p < 0.04, r: 0.35; p < 0.05, respectively). Only age and
      PHT were found to be independent predictors of MPV after regression analysis. The
      program substantially lowered BP (net reductions in systolic and diastolic BPs of
      16.2 and 8.7 mmHg, p < 0.001, p < 0.001, respectively). In addition, BMI, waist
      circumference (WC) and IR were significantly reduced in the PHT group (p < 0.01,
      p < 0.01, p < 0.05, respectively). At the end of study, although PLM, PLC values
      were reduced in the PHT group, only the decrease in MPV reached statistical
      significance (respectively, 10.41 +/- 0.93 fl vs. 9.67 +/- 1.2 fl, p < 0.01). In
      closing, to our best notice, our study is the first to display a significant
      increase in MPV in PHT subjects and to show a decrease in MPV by lifestyle
      modification after 20 weeks. As a result, we consider that decreased platelet
      activation with multi-aspect effects of lifestyle modification therapy might play
      an important role in reducing thrombotic risk in PHT patients.

PMID- 19172524
TI  - Acute profound thrombocytopenia with second exposure to eptifibatide associated
      with a strong antibody reaction.
AB  - We present a case of eptifibatide-induced acute profound thrombocytopenia in a 64
      year-old male receiving eptifibatide for the second time during percutaneous
      coronary intervention. Although rare, short and self-limited episodes of acute
      and profound thrombocytopenia have been associated with eptifibatide exposure.
      The thrombocytopenia is thought to be immune mediated, and assays are available
      to test for eptifibatide-induced platelet antibodies.

PMID- 19172525
TI  - Interpretation of the flag of platelet clumping from the Coulter LH 750.

PMID- 19172526
TI  - Effect of low-dose aspirin for skin rash associated with erlotinib therapy in
      patients with lung cancer.

PMID- 19172527
TI  - Absence of CYCS mutations in a large Italian cohort of patients with inherited
      thrombocytopenias of unknown origin.

PMID- 19172529
TI  - Factors contributing to performance on the Rey Complex Figure Test in individuals
      with traumatic brain injury.
AB  - When examining visual memory test results one must be aware of other variables
      that impact performance, particularly in individuals with traumatic brain injury
      who have broad cognitive deficits. The present investigation sought to determine
      the extent to which executive functioning, as operationally defined as perceptual
      organization, planning, and mental flexibility, impacted Rey Complex Figure Test
      (RCFT) performance. Results indicated that executive functioning measures
      accounted for between 11% and 16% of the variance in RCFT scores. ANCOVAs
      revealed that the relationship between degree of executive impairment and RCFT
      memory trials were non-significant when performance on the copy trial was
      controlled for. Furthermore, speed of processing and word reading were
      significantly related to RCFT performance. The predicted relationship with fine
      motor functioning was not supported. Implications and future research directions
      are discussed.

PMID- 19172530
TI  - Occurence of ultra-rapid cycling during electroconvulsive therapy in bipolar
      depression.
AB  - BACKGROUND: Treatment of bipolar depression with antidepressants has often been
      reported to be associated with a certain risk of rapid cycling (RC). Also, non
      pharmacological treatment approaches such as sleep deprivation or light therapy
      can induce affective shifts. Moreover, during electroconvulsive therapy (ECT),
      which is considered a powerful antidepressant treatment, manic switches and
      episodes of rapid cycling can occur. METHODS: Here we report the case of a 66
      year-old female patient with bipolar depression, who underwent electroconvulsive
      therapy because of a therapy-refractory depressive episode. RESULTS: During ECT,
      highly frequent mood alternations were observed, fulfilling the criteria of ultra
      rapid cycling (URC). These symptoms were successfully treated with lithium
      carbonate while ECT was continued. CONCLUSION: To our knowledge, this is the
      first case report of URC during ECT. URC might be considered a rare but potential
      side effect of ECT. In our case, lithium was used successfully for the treatment
      of URC and might be suggested in similar cases, where anticonvulsants are not the
      first choice of treatment. However, in view of the risk of cognitive side effects
      the combination of ECT and lithium requires a careful clinical monitoring.

PMID- 19172531
TI  - Using 3D-MRI to localize the dorsolateral prefrontal cortex in TMS research.
AB  - Transcranial magnetic stimulation (TMS) is currently used as a non-invasive
      treatment for depression. In most clinical trials, the left dorsolateral
      prefrontal cortex (DLPFC) has been selected as the target site for TMS treatment
      and this region is commonly determined by a "standard procedure", using a fixed
      position with respect to the motor cortex. In this study, to evaluate the
      relevance of using individual anatomical data during coil positioning, we used a
      more individualized localization method, based on three-dimensional magnetic
      resonance imaging of the head (3D-MRI). We wanted to examine the intra-individual
      variability of the localization of the stimulation area using a method taking
      into account individual brain anatomy by 3D-MRI, by comparing this method to the
      "standard procedure". As expected, even in a gender-controlled sample, our
      results demonstrate that the difference between the anatomical localization and
      the standard procedure of a well-defined part of the prefrontal cortex varies
      within subjects. Therefore, our results confirm the need for a TMS-coil
      positioning method which incorporates individual anatomical information.

PMID- 19172532
TI  - Relational property between head and eye regions is the primary determinant of
      the efficiency in search for a deviant gaze.
AB  - The human visual system is extremely sensitive to the directions of the gazes of
      others. However, the mechanism underlying gaze direction perception has yet to be
      clarified. The primary aim of the present study is to investigate whether the
      relational property between the local eye region and other facial regions serves
      as the primary visual system cue in detecting a direct gaze. Our results showed
      that search efficiency was determined primarily by the gaze direction indicated
      by the relational property regardless of the direction indicated by the local
      feature information of the eye region; this was true even when the gaze
      directions indicated by these two types of information were conflicting. These
      results bolster the hypothesis that the human visual system primarily accesses
      socially meaningful information in searching for a deviant gaze.

PMID- 19172533
TI  - Recurrent miscarriages: What is the role of cytokines?
AB  - Recurrent miscarriage is defined as three or more consecutive miscarriages before
      20 weeks of gestation. This condition is a frequent reproductive problem
      worldwide, affecting up to 1% of couples. Immune effector cell dysfunction has
      been implicated in the pathogenesis of early pregnancy loss. This dysfunction may
      involve defects in cytokines, growth factors and immunosuppressive factors at the
      maternofetal interface. This is a growing research field, especially the role of
      cytokines in recurrent miscarriage.

PMID- 19172534
TI  - Shorter CAG repeats in the androgen receptor gene may enhance hyperandrogenicity
      in polycystic ovary syndrome.
AB  - BACKGROUND: The main goal of the present study was to assess the influence of the
      androgen receptor gene CAG repeat polymorphism on hyperandrogenism and its
      phenotypical features in patients with polycystic ovary syndrome (PCOS). METHODS:
      CAG repeat lengths were analyzed in 97 oligo-anovulatory women with ultrasound
      features of PCOS. All individuals were assessed for endocrine parameters and
      their phenotypical features were recorded. These parameters were correlated with
      the CAG repeat lengths. RESULTS: PCOS patients with a bi-allelic mean lower than
      21 repeats had lower dihydrotestosterone levels (p = 0.007), lower
      androstenedione levels (p = 0.023), lower luteinizing hormone levels (p = 0.023),
      a lower luteinizing hormone/follicle-stimulating hormone ratio (p = 0.021) and
      the highest percentage of patients with acne and/or hirsutism (p = 0.021).
      CONCLUSIONS: Our findings support the hypothesis that the PCOS phenotype may
      result from either elevated androgen levels or an enhanced sensitivity to
      androgens caused by a more active androgen receptor.

PMID- 19172535
TI  - Effects of early luteal-phase vaginal progesterone supplementation on the outcome
      of in vitro fertilization and embryo transfer.
AB  - OBJECTIVE: To determine whether early luteal-phase vaginal progesterone
      supplementation improves the outcome of in vitro fertilization-embryo transfer
      (IVF-ET). METHODS: A randomized, controlled trial was conducted on 197 women
      undergoing IVF-ET cycles with human chorionic gonadotropin (hCG) as the standard
      luteal-phase support. The participants were randomly assigned to either the study
      group or the control group. The study group was given 200 mg micronized
      progesterone vaginally three times per day starting in the afternoon of oocyte
      retrieval until the morning of embryo transfer, in addition to the standard hCG
      luteal-phase support. The control group received only the hCG support. The
      pregnancy rates and the implantation rates were measured. RESULTS: There were no
      significant differences in pregnancy rates or implantation rates between groups.
      However, subgroup analysis revealed significantly higher pregnancy and
      implantation rates in the study group among those women with fibroids or
      difficult oocyte retrieval involving uterine puncture (38.7% vs. 15.4% and 26.8%
      vs. 9.4% respectively, both p = 0.04). CONCLUSION: Additional early luteal-phase
      vaginal progesterone supplementation may improve the outcome of IVF-ET in women
      with fibroids or difficult oocyte retrieval.

PMID- 19172536
TI  - Effects of estrogen therapy on microalbuminuria in healthy post-menopausal women.
AB  - OBJECTIVE: To evaluate the impact of estrogen therapy on microalbuminuria levels
      in healthy post-menopausal women. METHODS: Sixty post-menopausal women were
      evaluated in a prospective, randomised, double-blind, placebo-controlled study.
      The patients were randomly allocated to one of two groups to take one pill orally
      per day containing either 1 mg of 17beta-estradiol (E(2) group) or placebo
      (placebo group). Prior to initiating treatment and at the end of the sixth
      treatment month, microalbumin was measured in a 12-h urine sample, and lipid
      profile (total cholesterol, HDL, LDL and triglycerides) and fasting glucose were
      evaluated. Comparative intra- and inter-group analyses between the initial and
      final laboratory parameters were performed using the t-test for paired samples
      and for independent samples, respectively. RESULTS: Microalbuminuria levels
      remained within normal limits throughout the study and no statistically
      significant differences were found in the intra- or inter-group analyses. With
      respect to lipid profile, alterations characteristically encountered during use
      of estrogen replacement therapy were found. No statistically significant
      variation in glucose levels occurred during the study period. CONCLUSION:
      Estrogen replacement therapy had no significant effect on microalbuminuria levels
      in healthy post-menopausal patients.

PMID- 19172537
TI  - Levonorgestrel-releasing intrauterine system: why do some women dislike it?
AB  - BACKGROUND: There is growing evidence of women's dissatisfaction with the
      levonorgestrel-releasing intrauterine system (LNG-IUS) because of a high
      incidence of adverse effects. OBJECTIVE: To quantify the continuation rate and
      users' satisfaction, and identify symptoms associated with early removal before
      the 5-years effective life-time. METHOD: A questionnaire was sent to 212 women,
      who had LNG-IUS inserted from 1 January 1998 to 31 December 2003 at The Ipswich
      Hospital, UK. RESULTS: The response rate was 76% (n = 161), 16 of the respondents
      were excluded and the data of 145 are presented. The continuation rate was 85%,
      70%, 59%, 56%, 50% and 50% at 6 months, 1, 2, 3, 4 and 5 years, respectively. The
      total number of women who had the LNG-IUS removed before 5 years was 72 (50%),
      and the median duration of use was 270 days (range 4-1460). The reasons for early
      removal were unscheduled bleeding, progestogenic adverse effects, abdominal pain
      and others in 40 (28%), 32 (22%), 19 (13%) and 19 (13%) women, respectively. Only
      73 (50%) women were satisfied with LNG-IUS. CONCLUSIONS: Our findings are similar
      to recent reports, and this information should be readily available to women to
      enable them to make an informed choice.

PMID- 19172538
TI  - Effect of androgens combined with hormone therapy on quality of life in post
      menopausal women with sexual dysfunction.
AB  - AIM: To evaluate with validated instruments changes in quality of life and
      sexuality in women receiving hormonal replacement therapy (AHT). DESIGN:
      Randomised, double-blind, double-dummy study with two parallel treatment arms.
      PATIENTS AND METHODS: Forty-seven healthy post-menopausal women, aged 45-64
      years, were evaluated using the Female Sexual Function Index (FSFI) and the
      menopause-specific quality of life questionnaire (MENQOL). Of them, 40 diagnosed
      with sexual dysfunction were randomised (1:1) to receive daily 0.625 mg of
      conjugated estrogens plus 1.25 mg of methyl-testosterone and 100 mg of micronised
      progesterone or placebo. After 3 months follow-up, FSFI and MENQOL questionnaires
      were administered for a second time. RESULTS: Quality of life was unchanged in
      the placebo group whereas AHT significantly improved scores of vasomotor,
      psychological, physical and sexual symptoms. As expected, FSFI was not modified
      in the placebo group while in AHT group the FSFI score improved significantly. In
      addition, at the end of the study, 68.7% of subjects of the AHT group did not fit
      did not fit the criteria for sexual dysfunction as per the FSFI (p < 0.0001).
      CONCLUSIONS: Adding methyl-testosterone to hormone therapy improves quality of
      life and sexuality in post-menopausal women with sexual dysfunction.

PMID- 19172539
TI  - Coronary heart disease and HRT in France: MISSION study prospective phase
      results.
AB  - OBJECTIVE: To determine the morbidity incidence associated with Hormone
      Replacement Therapy (HRTs) in postmenopausal women. This paper presents the
      results concerning the incidence of coronary heart disease (CHD). DESIGN: MISSION
      study started on 5 January 2004, the cutoff for data collection was June 2006
      (follow-up no. 1). 'Exposed group': postmenopausal women currently on HRT,
      commonly prescribed in France or stopped < or =5 years previously. 'Unexposed
      group': never received HRT or stopped >5 years previously. RESULTS: Data were
      available for 4949 patients (without CHD at the beginning of the follow-up): 2693
      Exposed group and 2256 Unexposed group. The incidence during follow-up no. 1 of
      postmenopausal CHD was not significantly different in the Exposed group (0.11%)
      compared with the Unexposed group (0.13%). In the Exposed group the time between
      start of HRT and menopause was 2.93 +/- 4.46 years in those who experienced CHD
      and 1.53 +/- 3.20 years in those who had no incidence of CHD (p = 0.3).
      CONCLUSION: In the MISSION cohort, no increased risk of CHD was found in the
      Exposed group compared with the Unexposed group.

PMID- 19172540
TI  - A pilot study on the usefulness of body mass index and waist hip ratio as a
      predictive tool for gestational diabetes in Asian Indians.
AB  - Gestational diabetes mellitus (GDM) is a common public health issue of pregnancy
      and women who have had GDM are at high risk for developing of diabetes mellitus
      Type-2. The aim of this study was to find the association between various
      clinical and biochemical parameters and GDM. One hundred and six consecutive
      patients who attended the out patient unit of department of gynecology, Kottayam
      Medical College, were enrolled in the study and followed up through the whole
      antenatal, intra-partum and post-partum periods to identify the obstetric
      outcome. We found that the prevalence of GDM was seven times higher in those with
      higher waist-hip ratio (WHR > 0.85) compared with those having a lower WHR (p <
      0.001).Those with higher WHR gained more weight than other group (10.6 kg vs. 8.1
      kg; p < 0.001). Obesity (BMI > or =23) and higher WHR were associated with
      increased risk of gestational diabetes (BMI > or =23: OR = 7.5, CI 95% = (1.61
      34.31), p = 0.013; WHR > 0.85: OR = 12.05, CI 95% = (1.82-77.43), p = 0.007). We
      found that a WHR of 0.849 has the optimal sensitivity and specificity for the
      prediction of GDM. A waist circumference of 85.5 cm (with sensitivity of 75%,
      specificity 81.4%) and a BMI of 24.3 kg/m(2) (sensitivity 75%, specificity 86.5%)
      had the best predictive value. In conclusion, we found that maternal obesity has
      a strong correlation with obstetric complications. We found WHR is more important
      risk determinant for GDM in overweight/obese women than women with normal
      weight/lean.

PMID- 19172541
TI  - A novel mutation in exon8 of the follicle-stimulating hormone receptor in a woman
      with primary amenorrhea.
AB  - The FSH receptor (FSHR) gene mutation are rare, but recently have been detected
      in several cases with primary amenorrhea. We report a 25-year-old female who had
      primary amenorrhea, moderately developed secondary sex characteristics and normal
      sized ovaries with small antral follicles. Her ovaries reacted slightly to
      clomiphene citrate therapy; they did not react to the ordinary dose of human
      menopausal gonadotropin (hMG) (150 IU/day x 9 days), but did react to high-dose
      hMG (300 IU/day x 6 days) treatment. These ovarian responses to hMG stimulation
      suggested an FSHR dysfunction of her ovaries. We extracted genomic DNA and
      analysed FSHR gene sequence after we obtained the written informed consent from
      the patient under the approval by the Ethics Committee of Yamaguchi Grand Medical
      Centre and the Yamaguchi University School of Medicine. Direct sequencing
      revealed a heterozygous mutation 662T->G resulting in the substitution of valine
      for glycine at position 221 in exon8 of the FSHR extracellular domain, which was
      also confirmed by the PCR-RFLP method. The sequencing results also showed two
      SNPs, 919G->A (Ala307Thr) and 2039G->A (Ser680Asn), in exon10. A novel mutation
      in exon8 of FSHR was identified in a woman with primary amenorrhea whose ovaries
      reacted to high-dose hMG treatment.

PMID- 19172542
TI  - Molecular identification of chromosome Y sequences in Brazilian patients with
      Turner syndrome.
AB  - The investigation of Y-specific sequences in patients with Turner Syndrome (TS)
      with karyotype 45,X or mosaic, has a fundamental role in the clinical management
      of these patients. The relationship between the presence of Y chromosome
      fragments and a higher risk of gonadoblastoma in TS has already been established.
      The aim of the study was to investigate the presence of Y-chromosome fragments in
      a population of 42 female Brazilian patients with TS from Mato Grosso state.
      Cytogenetic analysis has shown the karyotypes 45,X in 27 of them (64.3%) and
      mosaic in 15 (35.7%). The presence of the Y-primers SRY, DYZ3, ZFY, DYZ1, DYS1
      and PABY was investigated in all patients. These markers were amplified by
      polymerase chain reaction (PCR) technique, using DNA genomic from peripheral
      blood lymphocytes. None of these patients had shown any Y-chromosome fragments
      when they were analysed only by the classic cytogenetic technique. The PCR
      analysis with the Y-specific sequences ZFY and DYZ3 were identified in two
      different patients (4.8%), both with karyotype 45,X. It was concluded that PCR is
      efficient in the investigation of hidden Y-fragments in TS patients. Therefore,
      this method should be included in the routine assistance of these patients.

PMID- 19172543
TI  - Effects of two estroprogestins containing ethynilestradiol 30 microg and
      drospirenone 3 mg and ethynilestradiol 30 microg and chlormadinone 2 mg on skin
      and hormonal hyperandrogenic manifestations.
AB  - Hyperandrogenic manifestation in women, such as seborrhea, acne and increased
      hair growth are common reasons of psychological distress. Skin appearance is very
      important for young women. This study evaluated the hormonal and skin effects of
      two estroprogestins (EPs) containing ethinyl-estradiol (EE) 30 microg associated
      with drospirenone (DRSP) 3 mg or chlormadinone acetate (CMA) 2 mg, respectively.
      Fifty-five women with signs and symptoms of hyperandrogenism (seborrhea, acne and
      increased hair growth) were enrolled in the study; randomly, 30 women were
      treated with EE 30 microg + DRSP 3 mg and 25 with EE 30 microg + CMA 2 mg.
      Follicle-stimulating hormone (FSH), luteinising hormone (LH), 17
      hydroxyprogesterone (17OHP), androstenedione (A), testosterone (T),
      dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG) and
      free androgen index (T x 100/SHBG, FAI) were assessed at baseline, and after 3
      and 6 months of treatment with EPs. Effects on seborrhea, acne and increased hair
      growth (as Ferriman-Gallwey score) were also evaluated at the same time points.
      Finally, skin hydration, transepidermal water loss (TEWL) and skin homogeneity
      were studied with non-invasive technique during the study. Treatment for 6 months
      with both EPs decreased significantly the circulating androgen levels (A, T,
      DHEAS) and FAI, and increased SHBG levels; also skin pattern was improved. EP
      containing EE and DRSP was better than EP containing EE and CMA as for skin
      changes, as seborrhea, acne, increased hair, hydration, homogeneity and overall
      quality of the skin; moreover, hormonal changes (as FAI) under therapy were more
      pronounced with EE/DRSP than EE/CMA. These effects may be considered in EP choice
      and could be important in improving patient's compliance and quality of life in
      hyperandrogenic women.

PMID- 19172544
TI  - Elevated level of plasma vascular endothelial growth factor after gonadotropin
      releasing hormone agonist treatment for leiomyomata.
AB  - OBJECTIVE: Uterine leiomyomata are the most common gynecological benign tumor and
      greatly affect reproductive health and well-being. The pathophysiology and
      epidemiology of fibroids are poorly understood. Gonadotropin-releasing hormone
      agonist (GnRH-a) pretreatment is one of the unfavourable factors for leiomyomata
      treatment with uterine artery embolisation (UAE). In this study, we investigated
      the plasma level of vascular endothelial growth factor (VEGF) in uterine
      leiomyoma patients with or without GnRH-a pretreatment. STUDY DESIGN: Thirty-two
      women who underwent UAE for symptomatic uterine leiomyoma were analysed. The
      plasma level of VEGF was studied before UAE. RESULTS: The level of plasma VEGF
      was significantly higher in the GnRH-a pretreated group compared with the non
      treated group. CONCLUSION: A compensative reaction for vasculature after GnRH-a
      treatment is speculated. Higher level of VEGF in GnRH-a pretreatment group could
      be one of the unfavourable factors for the treatment of uterine leiomyomata by
      UAE.

PMID- 19172545
TI  - Anabolic decline in the aging male: a situation of unbalanced syncrinology.

PMID- 19172546
TI  - Perioperative morbidity and mortality in 80 years and older undergoing elective
      urology surgery - a prospective study.
AB  - BACKGROUND AND PURPOSE: The number of octogenarians requiring surgery increases
      constantly. Data regarding perioperative morbidity and mortality in octogenarians
      is limited. Our aim was to assess surgery-related complications in octogenarians,
      undergoing urological surgery. PATIENTS AND METHODS: We prospectively collected
      data from octogenarians and a control group of younger patients undergoing an
      elective urological surgery in our institution. Recorded data included: age,
      gender, American Society of Anesthesiologists (ASA) score, co-morbidities, number
      of medications, operation extent, anaesthesia type, surgery duration and
      perioperative morbidity and mortality. RESULTS: Forty-seven octogenarians and 80
      patients with a median age of 59 years (range 19-75) enrolled prospectively.
      Gender ratio, surgeries extent and median operative time were similar among
      groups. General anaesthesia was more prevalent in the control group. ASA
      classification and duration of hospitalization were significantly higher in
      octogenarians. The rate of intra-operative complications was significantly higher
      in the octogenarians group 6.38% versus 3.75% (p = 0.007), there was no
      significant difference in immediate post-operative and post-discharge
      complications among groups. One octogenarian patient died 2 days post-surgery, no
      death occurred in the control group. CONCLUSIONS: Octogenarians have higher rate
      of intra-operative morbidity, leading to longer hospital stay. More experienced
      surgeons and anaesthetists should be involved in the operation; and careful
      surgical technique, tapered anaesthesia and higher level of post-operative
      monitoring should be applied for patients in this age.

PMID- 19172547
TI  - Salvage therapy trial for erectile dysfunction using phosphodiesterase type 5
      inhibitors and vitamin E: preliminary report.
AB  - We report our initial experience with salvage therapy for low responders to PDE-5
      inhibitors by adding vitamin E. Of 89 patients with ED who visited our clinic
      between January 2004 to August 2006, 9 were unable to obtain a full response to a
      PDE-5 inhibitor and included in the present study. After providing informed
      consent, each was given 300 mg per day of alpha-tocophenol at least 1 month and
      completed IIEF-5 questionnaires to assess its efficacy while also taking a PDE-5
      inhibitor. With alpha-tocophenol administration, the average IIEF-5 score
      increased from 13.8 +/- 3.2 to 17.1 +/- 3.6. Four of seven patients who completed
      the questionnaire each time showed improved IIEF-5 scores, with a maximum
      elevation of 9 points. Further, eight of the nine patients experienced favourable
      subjective changes, the majority being increased penile rigidity. The present
      clinical trial results are, to our knowledge, the first known to show the effects
      of vitamin E for enhancing the efficacy of a PDE-5 inhibitor.

PMID- 19172548
TI  - Testosterone supplementation for hypogonadal men by the nasal route.
AB  - Although multiple forms of testosterone replacement therapy are available to
      treat hypogonadism, none is ideal. This article reports on the pharmacokinetics
      of an innovative nasal formulation of testosterone in hypogonadal men. The first
      study was undertaken in eight men with a baseline total testosterone (TT) of
      130.8 +/- 87.4 ng/dL and examined the pharmacokinetics of nasal testosterone
      given in a single dose of 7.6 mg, 15.2 mg or 22.8 mg, respectively. The second
      study examined the pharmacokinetics of nasal testosterone (7.6 mg) given either
      twice or three times a day in 21 severely hypogonadal men (baseline TT in 20
      patients <50 ng/dL, in one patient 152 ng/dL) for 14 days. The steady-state
      concentration of testosterone was within the normal range in all treatment
      groups, but only in the 3-times-a-day group was the 95% confidence interval
      completely within the physiological range. The average DHT level did not exceed
      the upper range of normal. The clinical global visual analogue scale improved in
      the whole group receiving testosterone (p < 0.001). All adverse events in both
      studies were of mild to moderate intensity and were evaluated as unlikely or not
      related to the administered study drug. No patients dropped out during treatment.
      Comparison with the normal circadian rhythm by computer modelling suggests that
      nasal testosterone can be used to mimic the normal diurnal pattern in eugonadal
      men. Thus, nasal testosterone can be administered safely to humans in doses that
      approximate serum concentrations in the normal physiological range.

PMID- 19172549
TI  - The effects of environmental stressors on the mortality of the oldest old male
      population in Hong Kong, 1977-2006.
AB  - Although age-sex-specific mortality rates were decreasing over the years, such a
      trend was not observed for the male population aged 85 or above (the oldest old)
      in Hong Kong. Despite literature suggesting that environmental stressors were
      associated with higher mortality, the adverse effects of socioeconomic and
      political events were seldom included. Hence, this study explored the
      relationship between environmental stressors covering adverse weather conditions
      as well as key socioeconomic and political events and fluctuations in the oldest
      old mortality rates in Hong Kong during the period 1977 to 2006. The oldest old
      mortality rates in Hong Kong were observed to have a likelihood of being
      associated with these environmental stressors. Furthermore, men appeared to be
      more susceptible to these risk factors than did women. More care and attention
      should be given to the oldest old men, in particular, during periods of
      socioeconomic or political upheavals. A cohort study would be useful to study
      these stressors in greater detail.

PMID- 19172550
TI  - Baldness, benign prostate hyperplasia, prostate cancer and androgen levels.
AB  - INTRODUCTION: We evaluated the pattern of baldness and serum androgen levels in
      patients with benign prostate hyperplasia (BPH) and prostate cancer. BPH,
      prostate cancer and androgenic alopecia (AA) were somehow androgen dependent and
      affect large population of elderly men. MATERIAL AND METHOD: A total of 152
      patients, 108 patients with BPH and 44 patients with prostate cancer were
      included in the study. We measured serum total, free and bioavailable
      testosterone, FSH, LH, prolactin, estradiol, albumin and SHBG levels. Baldness
      classification was based on Norwood's classification and we categorised baldness
      as vertex and frontal baldness. RESULT: The frequency of AA in BPH and prostate
      cancer groups were not different. We looked for some correlation between the two
      groups with respect to AA and hormone levels. We did not find any correlation
      between AA and total testosterone, free testosterone, bioavailable testosterone
      or SHBG levels in both groups. CONCLUSION: This prospective study with selected
      small group of patients showed that there is no difference of male pattern
      baldness in BPH and prostate cancer patients and also there is no correlation
      between pattern of baldness and serum androgen levels.

PMID- 19172552
TI  - [Post-exposure prophylaxis of HIV infection. German-Austrian recommendations,
      update September 2007].

PMID- 19172551
TI  - Why can patients with erectile dysfunction be considered lucky? The association
      with testosterone deficiency and metabolic syndrome.
AB  - Metabolic syndrome (MetS) is a diagnostic category, based on a cluster of risk
      factors (hyperglycemia/diabetes, abdominal obesity, hypertriglyceridaemia, low
      HDL cholesterol and hypertension), which identifies subjects at high risk for
      forthcoming type 2 diabetes mellitus and cardiovascular (CV) diseases. Recently,
      a close association between MetS, erectile dysfunction (ED) and male hypogonadism
      has been reported. In patients with MetS, hypogonadism can exacerbate sexual
      dysfunction and arteriogenic ED because of its typical symptoms, such as
      decreased sexual desire and mood disturbances. On the other hand, hypogonadism
      per se has been associated with an increased risk of CV and overall mortality.
      Obesity and in particular central obesity is nowadays considered the most
      important determinant of MetS-induced hypogonadism whereas hypertension and
      diabetes play a major role in ED associated with MetS. This review analyses the
      current literature regarding the relationship between ED, MetS and hypogonadism
      emphasising the epidemiological and psychopathological aspects and stressing the
      concept that ED subjects are 'lucky', because ED offers a unique chance to
      undergo medical examination and therefore to improve not only their sexual but,
      most importantly, their overall health.

PMID- 19172553
TI  - [Diagnostic and treatment of HIV-affected couples who wish to have children].

PMID- 19172554
TI  - [Antiretroviral therapy of HIV infection. German-Austrian guidelines (position in
      September 2008)].

PMID- 19172555
TI  - [German-Austrian recommendations for HIV treatment during pregnancy and for
      newborns exposed to HIV--Update 2008].

PMID- 19172556
TI  - [Rupture of an abdominal aortic aneurysm].
AB  - Abdominal aortic aneurysms, i.e., enlargements of the abdominal aorta > 3 cm, are
      often the consequence of atherosclerotic vascular changes. Aneurysms of the
      abdominal aorta are often incidentally detected and asymptomatic. Expansion of
      the aneurysms are common and associated with an increased risk of rupture,
      resulting in a life-threatening situation. Here, we demonstrate the case of a 79
      year old man being admitted to the hospital for presyncope and repeated
      hypotension. Before finishing the diagnostic tests, the patient's situation
      suddenly worsened in the emergency room, due to rupture of a huge infrarenal
      aneurysm not known until then. Emergency surgery, however, was not successful,
      confirming the bad outcome for patients in this situation. Early diagnosis and
      surgical repair where appropriate are essential to affect prognosis of this
      disease.

PMID- 19172557
TI  - Atypical carcinoid of the larynx and potential complications of the carcinoid
      syndrome: a case report.
AB  - A 47-year-old man with a history of allergic rhinitis presented with a several
      month history of nasal symptoms and gastroesophageal reflux disease. He also had
      clinical depression, for which he had been taking a selective serotonin reuptake
      inhibitor (SSRI). During evaluation, flexible laryngoscopy incidentally detected
      a left interarytenoid polyp. Biopsy identified the lesion as a moderately
      differentiated neuroendocrine carcinoma. In addition to conducting a metastatic
      workup, we determined that it was necessary to evaluate the functional status of
      the tumor prior to excision because the SSRI could precipitate a carcinoid
      syndrome. We discuss the characteristics and management of different
      neuroendocrine carcinomas of the larynx, and we review the potential
      complications of the carcinoid syndrome.

PMID- 19172558
TI  - Tracheal diverticulum: a report of 4 cases.
AB  - Tracheal diverticulum is a rare entity. When it does occur, it is usually
      discovered incidentally in an asymptomatic patient as an outpouching from the
      tracheal wall, usually on the right side. It can be either congenital or
      acquired. A tracheal diverticulum may act as a reservoir for secretions that may
      spill over into the tracheobronchial tree, predisposing affected patients to
      cough, dyspnea, stridor, and chronic chest infection. The author describes 4
      cases of tracheal diverticulum--3 congenital and 1 acquired--that were discovered
      on chest x-ray. The congenital form was found incidentally in 3 asymptomatic
      middle-aged women, and the acquired case (a tracheobronchial diverticulum) was
      discovered during a workup for chronic cough and fever in a young man. All 4
      patients were thoroughly evaluated with conventional chest and neck radiographs,
      barium-swallow imaging, linear tomography, computed tomography, and magnetic
      resonance imaging. Resection of these tracheal diverticula was not considered for
      any patient. The author also reviews the literature on tracheal diverticulum.

PMID- 19172559
TI  - Chondroid metaplasia mimicking recurrent squamous cell carcinoma of the head and
      neck.
AB  - A 65-year-old woman presented with a "sore bump" on her tongue. She had a history
      of squamous cell carcinoma of the head and neck that had been treated with
      surgery and radiotherapy 11 years earlier. The tongue lesion was excised, and
      pathologic examination identified a submucosal focus of benign-appearing
      cartilage. No evidence of dysplasia or malignancy was seen. She was diagnosed
      with chondroid metaplasia. Chondroid metaplasia involving the head and neck is
      rare. When it has occurred, it has been seen in both reactive and neoplastic
      settings. To our knowledge, this is the first reported case of a chondroid
      metaplasia of the tongue.

PMID- 19172560
TI  - Malignant melanoma metastatic to the thyroid gland: a case report and review of
      the literature.
AB  - The thyroid gland is a relatively uncommon site for a secondary malignancy; even
      less common is a case of malignant melanoma metastatic to the thyroid. We
      describe the case of a 68-year-old man who presented with a neck mass in the
      posterior triangle. Fine-needle aspiration biopsy (FNAB) identified the mass as a
      malignant melanoma. The patient had had no known primary skin melanoma. He
      underwent a left modified radical neck dissection, and the mass was discovered to
      be a positive lymph node. Postoperatively, he declined to undergo radio- and
      chemotherapy. Eighteen months later, he returned with a diffusely enlarged
      thyroid. FNAB again attributed the enlargement to malignant melanoma. Soon
      thereafter, the patient began experiencing seizures, and on magnetic resonance
      imaging, he was found to have metastatic disease to the brain. He developed
      ventilator-dependent respiratory failure and required a subtotal thyroidectomy
      for the placement of a tracheostomy tube. Patients who present with a thyroid
      nodule and who have a history of malignancy present a diagnostic dilemma: Is the
      nodule benign, a new primary, or a distant metastasis? The findings of this case
      and a review of the literature strengthen the argument that any patient with a
      thyroid mass and a history of malignancy should be considered to have a
      metastasis until proven otherwise.

PMID- 19172561
TI  - Consistency of medical student education in otolaryngology.

PMID- 19172562
TI  - Extruding stapes prosthesis.

PMID- 19172563
TI  - Iatrogenic occipital osteomyelitis.

PMID- 19172564
TI  - Parathyroid carcinoma.

PMID- 19172565
TI  - Laryngeal saccular cyst in an infant.

PMID- 19172566
TI  - Your experience with pay-for-call reimbursement: results of a questionnaire
      survey.

PMID- 19172567
TI  - Asymmetric agenesis of the mastoid antrum in a neonate.
AB  - The authors report a case of asymmetric development of the mastoid antrum in a
      neonate. The lack of mastoid development most likely represents a congenital
      maldevelopment. Agenesis of the mastoid antrum has surgical implications, as
      failure to recognize its absence can result in disorientation during surgery,
      with potential to injure adjacent structures.

PMID- 19172568
TI  - Nonseptic lateral sinus thrombosis: the role of the otolaryngologist.
AB  - Nonseptic lateral sinus thrombosis differs from septic lateral sinus thrombosis
      in that it is not associated with ear or sinus infection. Mastoid changes are
      frequently detected on computed tomography or magnetic resonance imaging in cases
      of nonseptic lateral sinus thrombosis. An otolaryngologic evaluation is usually
      required to exclude coexisting mastoiditis.

PMID- 19172569
TI  - Depressed anterior table fracture: a minimally invasive method of reduction.
AB  - One-third of frontal sinus fractures are isolated to the anterior table.
      Traditional approaches to the reduction of an isolated anterior table fracture
      include the coronal incision, the bilateral brow incision, an endoscopic brow
      lift with an incision either directly over the fracture or in the brow, and
      delayed repair with a camouflaging implant. We describe a case involving a 14
      year-old boy with a depressed anterior table fracture that we successfully
      treated using a minimally invasive technique requiring only one 2-cm incision.

PMID- 19172570
TI  - Transfistula endoscopic closure of frontocutaneous fistula: a novel approach.
AB  - A fistula of the anterior table of the frontal sinus is an uncommon complication
      of acute frontal sinus abscess. Various methods to close a frontocutaneous
      fistula have been described. We present the second reported transfistula
      endoscopically assisted primary closure of a frontocutaneous fistula, which
      eliminated the need for major surgical intervention. We also review the etiology,
      pathogenesis, diagnosis, and management of frontocutaneous fistula.

PMID- 19172571
TI  - Vascular hamartoma of the paranasal sinuses: report of 3 rare cases and a short
      review of the literature.
AB  - The paranasal sinuses are an extremely unusual location for a vascular hamartoma.
      As far as we know, only 1 such case has been previously reported in the English
      language literature. We report 3 new cases of vascular hamartoma of the paranasal
      sinuses, which occurred in a 20-year-old woman and in 2 men aged 36 and 45 years.
      Radiologically, the lesion in the woman was confined to the sinuses, while
      evidence of intraorbital extension was seen in the 2 men. No intracranial
      extension was seen in any patient. The diagnosis was confirmed by histopathologic
      examination of the excised lesions. All 3 patients were alive without recurrence
      at 12 to 24 months of follow-up.

PMID- 19172572
TI  - Chondrosarcoma of the nasal septum.
AB  - Chondrosarcoma of the nasal septum is a rarely encountered malignancy. When it
      does occur, early diagnosis is difficult because patients generally present with
      common, nonspecific sinonasal complaints. We describe a case of chondrosarcoma of
      the nasal septum in a 38-year-old Hispanic man. The lesion was discovered on
      computed tomography during a workup for symptoms of chronic sinus disease. The
      tumor was removed in its entirety and identified as a low-grade lesion that
      required no further treatment. The patient remained disease-free 4 years
      postoperatively. We review the diagnosis of this neoplasm and its treatment and
      follow-up.

PMID- 19172573
TI  - An unusual presentation of Teflon granuloma: case report and discussion.
AB  - For more than 25 years, Teflon was the most commonly used material for injection
      laryngoplasty. However, the incidence of Teflon granuloma and the consequent
      deterioration of glottic function ultimately led to the development of other
      injectable materials, and as a result, Teflon granulomas are no longer frequently
      encountered. We present a case of Teflon granuloma that was unusual in that (1) a
      long period of time had elapsed between the injection and the granuloma formation
      and (2) there was no change in the patient's glottic function.

PMID- 19172574
TI  - Training in the primary prevention and early detection of oral cancer: pilot
      study of its impact on clinicians' perceptions and intentions.
AB  - In this pilot study, we tested a new program for training medical care providers
      in the primary prevention and early detection of oral cancer. The training
      program consisted of two modules: (1) oral cancer epidemiology and head and neck
      examinations for the early detection of oral cancer and (2) assessment and
      counseling of patients in tobacco cessation. On a pretraining questionnaire, the
      8 participating clinicians (3 primary care physicians, 4 ENT nurses, and 1
      physician assistant) indicated that they had only a limited awareness of oral
      cancer, that they generally did not routinely examine asymptomatic patients for
      oral cancer, and that they engaged in only a limited amount of risk
      assessment/counseling with their patients. On a post-training questionnaire, they
      indicated that their training had been well received and would prompt them to
      increase their efforts to examine their patients for early signs of oral cancer
      and to counsel them about its risks.

PMID- 19172575
TI  - Glycemic risk factors of diabetic vascular complications: the role of glycemic
      variability.
AB  - Achieving adequate targets relatively to all risk factors is considered a
      standard of care for patients with diabetes mellitus. To date, current guidelines
      underline the importance of the 'glucose triad' (post-prandial glucose, fasting
      plasma glucose and glycated haemoglobin) as the three glycemic factors that
      should be controlled in diabetes care; however, several literature data show that
      optimizing glycemic control needs achieving a control of glycemic variations. The
      objective of the present work is reviewing biological and clinical data
      supporting the role of glycemic variability, its measurement and relationship
      with the three other well-known glycemic risk factors and evidencing the areas
      that need further investigation. At last, we propose a simple model that
      summarizes the 'glucose triad' plus the 'new' risk factor glycemic variability
      (the 'Pyramid of the Risk').

PMID- 19172576
TI  - Continuous subcutaneous insulin infusion (CSII) 30 years later: still the best
      option for insulin therapy.
AB  - Thirty years after its introduction, the use of continuous subcutaneous insulin
      infusion (CSII) keeps increasing, especially among children and adolescents. The
      technique, when used properly, is safe and effective.Compared with traditional
      NPH-based multiple daily injections (MDI), CSII provides a small but clinically
      important reduction of HbA(1c) levels, diminishes blood glucose variability,
      decreases severe hypoglycaemic episodes and offers a better way to cope with the
      dawn phenomenon.Insulin analogues have improved the treatment of diabetes,
      eroding part of the place previously occupied by CSII, but CSII still remains the
      first option for patients experiencing severe hypoglycaemic episodes, high
      HbA(1c) values or marked glucose variability while being treated with optimized
      MDI. Furthermore CSII is better than MDI considering the effects on quality of
      life and the possibility to adjust insulin administration according to physical
      activity or food intake.CSII may be limited by cost. Present estimates suggest
      that CSII may be cost-effective just for patients experiencing a marked
      improvement in HbA(1c) or a decrease in severe hypoglycaemic episodes, but the
      effects on quality of life are difficult to measure.CSII does not merely imply
      wearing an external device; it requires a multidisciplinary team, intensive
      patient education and continuous follow up.

PMID- 19172577
TI  - Novel injectable gel (system) as a vehicle for human articular chondrocytes in
      cartilage tissue regeneration.
AB  - We developed a novel injectable carrageenan/fibrin/hyaluronic acid-based hydrogel
      with in situ gelling properties to be seeded with chondrogenic cells and used for
      cartilage tissue engineering applications. We first analysed the distribution
      within the hydrogel construct and the phenotype of human articular chondrocytes
      (HACs) cultured for 3 weeks in vitro. We observed a statistically significant
      increase in the cell number during the first 2 weeks and maintenance of cell
      viability throughout the cell culture, together with the deposition/formation of
      a cartilage-specific extracellular matrix (ECM). Taking advantage of a new in
      vivo model that allows the integration between newly formed and preexisting
      cartilage in immunodeficient mice to be investigated, we showed that injectable
      hydrogel seeded with human articular chondrocytes was able to regenerate and
      repair an experimentally made lesion in bovine articular cartilage, thus
      demonstrating the potential of this novel cell delivery system for cartilage
      tissue engineering.

PMID- 19172578
TI  - Organization of nucleobase-functionalized beta-peptides investigated by soft
      electrospray ionization mass spectrometry.
AB  - The development and validation of analytical methods is a key to succeed in
      investigating noncovalent interactions between biomolecules or between small
      molecules and biomolecules. Electrospray ionization mass spectrometry (ESI-MS)
      was applied with a Fourier transform ion cyclotron resonance mass spectrometer
      (FTICR-MS) as well as a quadrupole/time-of-flight tandem mass spectrometer (QqToF
      MS) for a systematic investigation of noncovalent complexes based on nucleobase
      pairing in an artificial and noncharged backbone topology. Synthetical beta
      peptide helices covalently modified with nucleobases were organized by
      recognition of a sequence of four nucleobases. Specific duplexes of beta-peptide
      helices were obtained on the basis of hydrogen bonding base pair complementarity.
      Oligomer interactions were detected with defined stoichiometry and sensitivity
      for the respective duplex stability. FTICR-MS and QqToF-MS were used equally well
      to indicate double strand stabilities in agreement with the dissociation data
      determined by UV spectroscopy. Furthermore, the dissociation energies of gas
      phase ions of the noncovalent complexes were analyzed with collision induced
      dissociation (CID)-MS/MS and infrared multiphoton dissociation (IRMPD)-MS/MS. The
      CID conditions turned out to be too harsh for a differentiation of the duplex
      stabilities, whereas IRMPD might be developed as a technique to detect even small
      interaction energy differences.

PMID- 19172579
TI  - Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize
      platinum-resistant ovarian cancer cells to paraplatin.
AB  - Polyphenolic extracts of the principal flavonoid classes present in cranberry
      were screened in vitro for cytotoxicity against solid tumor cells lines,
      identifying two fractions composed principally of proanthocyanidins (PACs) with
      potential anticancer activity. Matrix-Assisted Laser Desorption/Ionization Time
      Of-Flight Mass Spectrometry (MALDI-TOF-MS) analysis of the proanthocyanidins
      (PACs) fractions indicated the presence of A-type PACs with 1-4 linkages
      containing between 2-8 epicatechin units with a maximum of 1 epigallocatechin
      unit. PACs exhibited in vitro cytotoxicity against platinum-resistant human
      ovarian, neuroblastoma and prostate cancer cell lines (IC50 = 79-479 microg/mL)
      but were non-cytotoxic to lung fibroblast cells (IC50 > 1000 microg/ml). SKOV-3
      ovarian cancer cells treated with PACs exhibited classic apoptotic changes. PACs
      acted synergistically with paraplatin in SKOV-3 cells. Pretreatment of SKOV-3
      cells with PACs (106 microg/ml) resulted in a significant reduction of the
      paraplatin IC50 value. Similarly, in a BrdU incorporation assay, co-treatment of
      SKOV-3 cells with PACs and paraplatin revealed reduced cell proliferation at
      lower concentrations than with either individually. In SKOV-3 cell cultures co
      treated with PAC-1 and paraplatin, an HPLC analysis indicated differential
      quantitative presence of various PAC oligomers such as DP-8, -9, -11 and -14
      indicating either selective binding or uptake. Cranberry proanthocyanidins
      exhibit cell-line specific cytotoxicity, induce apoptotic markers and augment
      cytotoxicity of paraplatin in platinum-resistant SKOV-3 ovarian cancer cells.

PMID- 19172580
TI  - Astragalus membranaceus prevents daunorubicin-induced apoptosis of cultured
      neonatal cardiomyocytes: role of free radical effect of Astragalus membranaceus
      on daunorubicin cardiotoxicity.
AB  - Anthracyclines are antitumor antibiotics with significant activity against solid
      and hematologic malignancies. One problem preventing more widespread use has been
      the development of cardiotoxicity. To determine whether antioxidant agents can
      reduce the cardiotoxicity of anthracyclines, a herb Astragalus membranaceus was
      introduced, which has been widely used for the treatment of cardiovascular
      diseases in China and was confirmed to be an effective antioxidant agent
      recently. Pre-treatment with Astragalus membranaceus significantly attenuated the
      daunorubicin-induced increases of reactive oxygen species (p < 0.001), apoptosis
      (p < 0.05) and the secretions of LDH (p < 0.01) in cultured neonatal
      cardiomyocytes. Astragalus membranaceus also raised the EC(50) of daunorubicin
      1.24-fold. Compared with Astragalus membranaceus, N-acetyl-L-cysteine had similar
      effects on daunorubicin-induced cell injury, however, superoxide dismutase
      reduced reactive oxygen species without attenuating apoptosis. The subcellular
      distribution of DNR was similar to the distribution of MitoTracker Red 580 in
      mitochondria, which was mainly in the cytoplasm around the nuclear membrane in
      cultured neonatal cardiomyocytes. In conclusion, the results suggested that
      Astragalus membranaceus is potentially protective against daunorubicin
      cardiotoxicity by decreasing free radical release and apoptosis in cultured
      neonatal cardiomyocytes. The main subcellular distribution of daunorubicin may be
      in the mitochondria.

PMID- 19172582
TI  - 1-methyl malate from Berberis integerrima fruits enhances the antibacterial
      activity of ampicillin against Staphylococcus aureus.
AB  - The enhancement of the antibacterial activity of ampicillin by different extracts
      of Berberis integerrima fruits was evaluated against Staphylococcus aureus. Disk
      diffusion and agar dilution methods were used to determine the antibacterial
      activity of ampicillin in the absence and presence of different plant extracts or
      various fractions eluted by column chromatography. A clinical isolate of S.
      aureus was used as a test strain. The active component of B. integerrima fruits
      involved in the enhancement of ampicillin activity was purified and identified as
      1-methyl malate using different spectroscopic methods. Both the ethanol extract
      of B. integerrima fruits and 1-methyl malate enhanced the antibacterial activity
      of ampicillin. The total extract as well as 1-methyl malate increased the
      antibacterial activity of ampicillin against the test strain. The potency of
      ampicillin against the test strain was increased 64-fold when tested with a sub
      toxic concentration of total extract of B. integerrima fruits. Also, 1-methyl
      malate increased the bactericidal activity of ampicillin. In the presence of 2
      mg/mL of 1-methyl malate the MIC of ampicillin for S. aureus decreased from 128
      to 1 microg/mL (128-fold).

PMID- 19172581
TI  - Antihyperlipidemic compounds from the fruit of Piper longum L.
AB  - A bioassay-guided isolation of an ethanol extract of the fruit of Piper longum L.
      yielded piperlonguminine, piperine and pipernonaline, as the main
      antihyperlipidemic constituents. They exhibit appreciable antihyperlipidemic
      activity in vivo, which is comparable to that of the commercial
      antihyperlipidemic drug, simvastatin.

PMID- 19172583
TI  - Accelerated antioxidant bioavailability of OPC-3 bioflavonoids administered as
      isotonic solution.
AB  - The degree of absorption of bioflavonoids, a diverse and complex group of plant
      derived phytonutrients, has been a frequent debate among scientists. Monomeric
      flavonoid species are known to be absorbed within 2 h. The kinetics of plasma
      reactive oxygen species, a reflection of bioactivity, of a commercial blend of
      flavonoids, OPC-3 was investigated. OPC-3 was selected to compare absorption of
      an isotonic flavonoid solution vs tablet form with the equivalent amount of
      fluid. In the case of isotonic OPC-3 the reactive oxygen species of the subject's
      plasma decreased significantly (p < 0.05), six times greater than OPC-3 tablets
      by 10 min post-consumption. After 20 min the isotonic formulation was
      approximately four times more bioavailable and after 40 min twice as bioavailable
      as the tablet, respectively. At time points 1 h and later, both isotonic and
      tablet formulations lowered oxidative stress, although the isotonic formulation
      values remained significantly better throughout the investigation period of 4 h.
      These findings point to a dramatically accelerated bioavailability of flavonoids
      delivered in an isotonic formulation.

PMID- 19172585
TI  - Mechanism of protective action of mangiferin on suppression of inflammatory
      response and lysosomal instability in rat model of myocardial infarction.
AB  - Lysosomal instability has been suggested as a major factor in the development of
      cellular injury during myocardial necrosis through the formation of inflammatory
      mediators. The present study was designed to investigate the effect of mangiferin
      on lysosomal hydrolases and TNF-alpha production during isoproterenol (ISPH)
      induced myocardial necrosis in rats. The rats given ISPH (200 mg/kg body weight
      twice, subcutaneous) for 2 days showed a significant increase in plasma TNF-alpha
      production, serum and heart lysosomal hydrolases activity. ISPH administration to
      rats resulted in decreased stability of the membranes, which was reflected by the
      lowered activity of cathepsin-D and beta-glucuronidase in mitochondrial, nuclear,
      lysosomal and microsomal fractions. Pretreatment with mangiferin (100 mg/kg body
      weight, intraperitoneally) for 28 days, significantly prevented the alterations
      and restored the enzyme activities to near-normal status. These findings
      demonstrate that mangiferin could preserve lysosomal integrity through decrease
      in the inflammatory process and hence establish the cardioprotective effect of
      mangiferin.

PMID- 19172584
TI  - Predictors of contralateral breast cancer in patients with unilateral breast
      cancer undergoing contralateral prophylactic mastectomy.
AB  - BACKGROUND: Although contralateral prophylactic mastectomy (CPM) reduced the risk
      of contralateral breast cancer in unilateral breast cancer patients, it was
      difficult to predict which patients were most likely to benefit from the
      procedure. The objective of this study was to identify the clinicopathologic
      factors that predict contralateral breast cancer and thereby inform decisions
      regarding performing CPM in unilateral breast cancer patients. METHODS: A total
      of 542 unilateral breast cancer patients who underwent CPM at The University of
      Texas M. D. Anderson Cancer Center from January 2000 to April 2007 were included
      in the current study. A logistic regression analysis was used to identify
      clinicopathologic factors that predict contralateral breast cancer. RESULTS: Of
      the 542 patients included in this study, 25 (5%) had an occult malignancy in the
      contralateral breast. Eighty-two patients (15%) had moderate-risk to high-risk
      histologic findings identified at final pathologic evaluation of the
      contralateral breast. Multivariate analysis revealed that 3 independent factors
      predicted malignancy in the contralateral breast: an ipsilateral invasive lobular
      histology, an ipsilateral multicentric tumor, and a 5-year Gail risk >or=1.67%.
      Multivariate analysis also revealed that an age >or=50 years at the time of the
      initial cancer diagnosis and an additional ipsilateral moderate-risk to high-risk
      pathology were independent predictors of moderate-risk to high-risk histologic
      findings in the contralateral breast. CONCLUSIONS: The findings indicated that
      CPM may be a rational choice for breast cancer patients who have a 5-year Gail
      risk >or=1.67%, an additional ipsilateral moderate-risk to high-risk pathology,
      an ipsilateral multicentric tumor, or an ipsilateral tumor of invasive lobular
      histology.

PMID- 19172586
TI  - (13)C CP MAS NMR of halogenated (Cl, Br, I) pharmaceuticals at ultrahigh magnetic
      fields.
AB  - This work reports significantly improved spectral resolution of (13)C CP MAS NMR
      spectra of chlorinated, brominated and iodinated solid organic compounds when
      such spectra are recorded at ultrahigh magnetic field strengths. The cause of
      this is the residual dipolar coupling between carbon atoms and quadrupolar
      halogen nuclides (chlorine-35/37, bromine-79/81 or iodine-127), an effect
      inversely proportional to the magnetic field strength which declines in
      importance markedly at 21.1 T as compared to lower fields. In favorable cases,
      the fine structure observed can be used for spectral assignment, e.g. for Cl
      substituted aromatics where the substituted carbon as well as the ortho-carbons
      show distinct doublets. The experimental results presented are supported by
      theoretical modeling and calculations. The improved spectral resolution in the
      studied systems and similar halogenated materials will be of particular interest
      and importance for polymorph identification, drug discovery and quality control
      in the pharmaceutical industry.

PMID- 19172587
TI  - In situ proton NMR study of acetyl and formyl group migration in mono-O-acyl D
      glucose.
AB  - Acetyl and formyl group migration, mutarotation, and hydrolysis of mono-O
      acylated glucose are studied by in situ 1D and 2D (1)H NMR spectroscopy. Alpha-D
      glucosyl-1-acetate and alpha-D-glucosyl-1-formate serve as sole starting
      materials. They are generated in situ by configuration retaining glucosyltransfer
      from alpha-D-glucosyl-1-phosphate to formate and acetate, which is catalyzed by
      the Glu-237 --> Gln mutant of Leuconostoc mesenteroides sucrose phosphorylase.
      Temporary accumulated regio-isomeric mono-O-acyl D-glucoses are identified,
      characterized, and quantified directly from the reaction mixture. Time courses of
      the transformations give insight into pH dependence of acyl group migration and
      mutarotation as well as into the stability of various regioisomers.

PMID- 19172588
TI  - Accuracy in planar cutting of bones: an ISO-based evaluation.
AB  - BACKGROUND: Computer- and robot-assisted technologies are capable of improving
      the accuracy of planar cutting in orthopaedic surgery. This study is a first step
      toward formulating and validating a new evaluation methodology for planar bone
      cutting, based on the standards from the International Organization for
      Standardization. METHODS: Our experimental test bed consisted of a purely
      geometrical model of the cutting process around a simulated bone. Cuts were
      performed at three levels of surgical assistance: unassisted, computer-assisted
      and robot-assisted. We measured three parameters of the standard ISO1101:2004:
      flatness, parallelism and location of the cut plane. RESULTS: The location was
      the most relevant parameter for assessing cutting errors. The three levels of
      assistance were easily distinguished using the location parameter. CONCLUSIONS:
      Our ISO methodology employs the location to obtain all information about
      translational and rotational cutting errors. Location may be used on any osseous
      structure to compare the performance of existing assistance technologies.

PMID- 19172594
TI  - Effect of perceived anonymity in assessments of eating disordered behaviors and
      attitudes.
AB  - OBJECTIVE: The present study assessed the effect of perceived anonymity on
      endorsements of eating disordered behaviors and attitudes across multiple
      response formats. METHOD: Four hundred sixty-nine undergraduate women responded
      using one of three questionnaire formats: a nominally anonymous true/false
      condition, an unmatched count condition, or a randomized-response condition. Both
      the unmatched count and randomized response conditions provided complete response
      anonymity. RESULTS: Significantly different endorsement rates were found for the
      majority of items when comparing the standard and unmatched count conditions,
      whereas differences were found for fewer items when comparing the standard and
      randomized response conditions. Perceived anonymity significantly differed across
      conditions, with the highest and lowest perceptions of anonymity found for the
      unmatched count and standard conditions, respectively. DISCUSSION: Perceived
      anonymity and response format affect endorsements of eating disordered behaviors
      and attitudes, highlighting the necessity of understanding factors that
      contribute to response bias.

PMID- 19172595
TI  - Negative reinforcement eating expectancies, emotion dysregulation, and symptoms
      of bulimia nervosa.
AB  - OBJECTIVE: Research suggests that emotion dysregulation or difficulties in the
      modulation of emotional experience constitute risk for eating disorders. Recent
      work has also highlighted the role of certain eating-related cognitions,
      specifically expectations of negative emotional reinforcement from eating, in the
      development of disturbed eating patterns. However, it is unclear whether these
      expectancies are merely a dimension of a general inability to regulate emotions
      effectively or rather a unique cognitive-affective risk factor for the
      development of an eating disorder. This study examines the unique contribution of
      eating expectancies to symptoms of bulimia nervosa (BN) after controlling for two
      dimensions of emotion dysregulation (alexithymia and experiential avoidance)
      previously implicated in the phenomenology of eating disorders. METHOD:
      Participants were 115 undergraduate women who self-reported demographics,
      alexithymia, experiential avoidance, eating expectancies, and symptoms of BN.
      RESULTS: Eating expectancies uniquely contributed 12.4% of the variance in
      symptoms of BN, F(2, 108) = 11.74, p < .001. The final model was statistically
      significant, F(6, 108) = 13.62, p < .001, and accounted for 40.0% of the variance
      in symptoms of BN. DISCUSSION: These results suggest that individuals who expect
      eating to provide emotional relief may be especially susceptible to disordered
      eating. Findings are discussed in terms of emotional risk models and clinical
      interventions for BN.

PMID- 19172596
TI  - Stress-induced laboratory eating behavior in obese women with binge eating
      disorder.
AB  - OBJECTIVE: To compare the microstructural eating behavior of obese patients with
      and without binge eating disorder (BED) after stress induction in laboratory.
      METHOD: Forty-eight obese women were investigated. Seventeen were assigned to the
      group of BED. Group (BED vs. non-BED) by condition (stress vs. no stress)
      interaction effect on feeding variables, measured by a universal eating monitor,
      was tested. Stress was induced by the trier social stress test (TSST) and
      chocolate pudding served as laboratory food. RESULTS: From the nonstress to the
      stress condition, patients with BED, when compared with non-BED had a greater
      increase in average eating rate (p < .01) and a corresponding greater increase in
      the frequency of spoonfuls (p < .02). The BED group also showed a different
      change in acceleration/deceleration from the nonstress to the stress condition
      compared to the non-BED group (p < .04). DISCUSSION: Obese individuals with BED
      appear to exhibit a different response to stress than obese non-BED individuals
      and individuals with bulimia nervosa.

PMID- 19172597
TI  - Competition affects food choice in women.
AB  - OBJECTIVE: To examine women's food choices after exposure to a threatening upward
      social comparison in an achievement situation. METHOD: Female university students
      performed three tasks in the presence of a confederate; for some, the situation
      was competitive and they were made to feel the confederate was likely to
      outperform them, whereas the remainder performed under noncompetitive
      circumstances. After completing the tasks, all participants chose a food to eat
      in a supposedly unrelated taste test. RESULTS: It was expected and found that
      participants in the high threat condition, in comparison with those in a low
      threat condition, would be highly motivated to restore their sense of self-worth
      by successfully competing in an area unrelated to the original inferiority and
      would, therefore, choose a lower calorie/more nutritious food. A secondary
      analysis revealed that it was primarily dieters whose food choices were affected
      by the threat. DISCUSSION: For dieters, competition by means of food choice can
      provide a means of restoring self-regard when self-esteem has been threatened in
      some other domain.

PMID- 19172598
TI  - Rosuvastatin positively changes nerve electrophysiology in diabetic rats.
AB  - OBJECTIVE: To examine the effect of rosuvastatin on peripheral nerve function in
      diabetic rats using electrophysiological measurements. BACKGROUND: Diabetes was
      induced in 5-day-old male Wistar rats by intraperitoneal (i.p.) injection of
      streptozotocin (STZ). As many as 45 diabetic rats were randomized to three
      groups: one treated with rosuvastatin (group R), another with rosuvastatin and
      mevalonate (group MR) and the other was untreated (group U). The data were
      compared with a group of normal age-matched rats i.e. control rats (group C).
      METHODS: Neurophysiological measurements were performed at the age of 3 months
      (T1) and again at the age of 8 months (T2), after 3 months of treatment. RESULTS:
      At T1, there was a trend to lower amplitude of compound motor action potential
      (CMAP) in the three diabetic groups as compared to controls, and no difference
      for motor nerve conduction velocity (MNCV), amplitude of sensory nerve action
      potential (SNAP), sensory nerve conduction velocity (SNCV) between diabetic
      groups and controls. At T2, the amplitude of CMAP was significantly lower in
      groups R and MR versus group U and control rats. MNCV was significantly and
      similarly decreased in the three diabetic groups; the latency of the first
      sensory peak (fastest sensory fibres) was significantly increased in group U but
      was normal in groups R and MR. CONCLUSIONS: This study shows that: 1.rosuvastatin
      exerts a beneficial effect on the conduction of the fastest sensory
      fibres;2.these effects are independent of blood pressure and lipid changes.

PMID- 19172599
TI  - Effect of compost and casing treatments of insecticides against the sciarid
      Bradysia ocellaris (Diptera: Sciaridae) and on the total yield of cultivated
      mushrooms, Agaricus bisporus.
AB  - BACKGROUND: Bradysia ocellaris (Comstock) is one of the major pests of cultivated
      mushrooms, Agaricus bisporus (Lange) Imbach. The feeding of sciarid fly larvae
      causes damage to the cultivation substrates, compost and casing. A comparative
      study of insecticidal treatments incorporated into compost and casing against B.
      ocellaris was conducted during 2003-2004. Treatments with an organophosphate,
      diazinon, a pyrazole, fipronil, and an insect growth regulator (IGR),
      triflumuron, were incorporated into casing. Another IGR, cyromazine, was
      incorporated into compost. Insecticidal incorporation into compost and casing has
      been associated with reductions in mushroom yield. Therefore, the effect of these
      insecticidal treatments on the overall yield was evaluated. RESULTS: A combined
      treatment, incorporation of cyromazine at 10 mg kg(-1) into compost and of
      triflumuron at 20 mg kg(-1) into casing, provided 100% control against B.
      ocellaris. There was no apparent reduction in yield as a result of incorporation
      of the tested chemicals into either compost or casing. CONCLUSION: The results
      obtained from this study suggest that incorporation of insecticides into both
      compost and casing is required to control a moderate to high pressure of insect
      pests. There were no significant yield reductions as a result of the
      incorporation of pesticides in the Australian mushroom-growing system.

PMID- 19172600
TI  - Health care utilization in patients with eating disorders.
AB  - OBJECTIVE: To examine health care costs among patients with eating disorders
      (EDs) using the Blue Cross Blue Shield of North Dakota claims database system.
      METHOD: Four groups of individuals enrolled between 1999 and 2005 were
      identified: (1) a group diagnosed with EDs at the beginning of the study period,
      in 2000 or 2001; (2) a group diagnosed with EDs later in the study period, in
      2004 or 2005; (3) a comparison group with depression; and (4) a non-eating
      disordered comparison group. RESULTS: Health care costs were high for patients
      diagnosed with an ED during the period when the diagnosis was made but remained
      elevated in the years following. Such costs were consistently higher than those
      for the non-eating disordered comparison group, but similar to the depression
      comparison group. DISCUSSION: Health care costs remained elevated after a
      diagnosis of an ED for an extended period of time.

PMID- 19172602
TI  - Coming soon to the Laryngoscope: papers from the American Laryngological Society.

PMID- 19172603
TI  - Defining the nasopalatine line: the limit for endonasal surgery of the spine.
AB  - OBJECTIVES: The expanded endoscopic endonasal approach (EEA) to the odontoid
      process is performed for decompression of the brainstem and to access tumors at
      the foramen magnum. Caudal exposure is limited by the nasal bones anteriorly and
      the hard palate posteriorly. We define the line connecting these two points as
      the nasopalatine line (NPL) and the nasopalatine angle (NPA) as the angle between
      the nasopalatine line and the plane of the hard palate. STUDY DESIGN: This study
      was a retrospective cohort study. METHODS: Pre and post-operative computed
      tomographic (CT) scans of 17 patients who underwent transodontoid EEA were
      reviewed. The position of the odontoid and the inferior extent of the tumor and
      surgical dissection were compared to the NPL. Factors affecting the posterior
      projection of the NPL, including basilar invagination and head position, were
      examined. RESULTS: The mean NPA was 27.1 degrees (range 21-31 degrees ). The NPL
      intersects the spinal column at 8.9 mm (range -9.0-8.7 mm) above the base of the
      C2 body. The base of the odontoid process and the inferior extent of surgical
      dissection were always above this line. Both basilar invagination and head
      position affect the relative position of the NPL. Patients with basilar
      invagination demonstrated a significantly lower posterior projection of the NPL
      than those without (P < .01). Maximal cervical flexion afforded more caudal
      exposure than cervical extension. CONCLUSIONS: The NPL accurately predicts the
      most inferior extent of surgical dissection. Further caudal dissection may
      require the use of angled instruments or a transoral approach.

PMID- 19172604
TI  - Combined atresiaplasty and tragal reconstruction for microtia and congenital
      aural atresia: thesis for the American Laryngological, Rhinological, and
      Otological Society.
AB  - OBJECTIVE: To describe a new technique for combining atresiaplasty with tragal
      reconstruction by performing the tragal reconstruction with cartilage grafting at
      the same time as the atresiaplasty for patients with microtia and congenital
      aural atresia. Hearing and canaloplasty outcomes for this combined technique are
      reported. PATIENTS: Patients with aural atresia (n = 19) with (n = 16) or without
      (n = 3) microtia, and a Jahrsdoerfer grade of 6 or higher. Mean age was 8.3
      years. Atresiaplasty was performed in 20 ears, with the new combined technique in
      15 ears (75%). METHODS/INTERVENTIONS: During the meatoplasty portion of
      atresiaplasty, the tragus was reconstructed with a cartilage graft and an
      anteriorly pedicled skin flap. OUTCOME MEASURES: Hearing results, complications
      including canal stenosis, infections, sensorineural hearing loss, and facial
      nerve injuries. RESULTS: The mean postatresiaplasty pure tone average (PTA) and
      air bone gap (ABG) were 37.5 and 29.4 dB, respectively. Eleven (55%) of the ears
      had an ABG of < or =30 dB, and 10 (50%) had speech reception thresholds (SRT) of
      < or =30 dB. Six ears (30%) had postoperative infections. Revision surgery was
      performed in four ears (20%) for canal/meatal stenosis, and in six (30%) for
      conductive hearing loss. Bone Anchored Hearing Aid was performed in six patients
      (30%). There was no sensorineural hearing loss or facial nerve injury.
      CONCLUSIONS: The new combined tragal reconstruction and atresiaplasty technique
      yielded satisfactory hearing, canal/meatal patency, and cosmetic results, with
      acceptable rates of complications. This combined tragal reconstruction and
      atresiaplasty technique is a valuable option in the armamentarium of microtia and
      atresia surgeons.

PMID- 19172608
TI  - Percutaneous tracheotomy in otolaryngology-head and neck surgery residency
      training programs.
AB  - OBJECTIVES: Percutaneous tracheotomy (PT) has been garnering attention in
      otolaryngology-head and neck surgery (OTO-HNS) community for many years. This
      procedure is used routinely by a variety of surgical disciplines; yet its use
      remains controversial especially in OTO-HNS. The purpose of this study is to
      understand the current practices pertaining to PT in OTO-HNS training programs.
      STUDY DESIGN: Multi-institution physician survey. METHODS: A survey of 102
      American OTO-HNS residency program directors. RESULTS: The response rate was 80%.
      29% of programs perform PT on a regular basis. Ciaglia Blue Rhino method was used
      by all respondents who could identify the method used. Simultaneous video
      bronchoscopy was always used by 91% of those who performed PT. Among respondents
      in programs where PT was not done regularly, 18% felt that it was the method of
      choice for selected patients; among those in programs where PT was done
      regularly, 72% felt that it was the method of choice. 64% of respondents
      indicated that other hospital services regularly performed PT in their
      institution, and this was evenly split between trauma, general surgery,
      pulmonology and intensive care unit (ICU). There was no significant difference in
      this regard between respondents from hospitals that did or did not do PT. 71% of
      OTO-HNS graduates are not trained in PT. CONCLUSIONS: Only 29% of otolaryngology
      residency programs in the U.S. perform PT regularly. This study objectively shows
      that this is a highly polarized subject amongst OTO-HNS but apparently not in
      medicine in general. Further study is needed to understand the reason for this
      controversy.

PMID- 19172609
TI  - Dural arteriovenous fistula: diagnosis, treatment, and outcomes.
AB  - OBJECTIVES: The objective of this study is to determine the sensitivity of
      computed tomography angiography (CTA) and magnetic resonance angiography (MRA)
      compared to the gold standard, conventional carotid angiography, in the diagnosis
      of a dural arteriovenous fistula (DAVF). Further objectives include identifying
      outcomes of treatment and complications as a function of pretreatment radiologic
      classification. STUDY DESIGN: This is a retrospective review of adults diagnosed
      with a DAVF between 1990 and 2006. METHODS: Data collected included age, gender,
      presenting clinical symptoms, diagnostic imaging modalities (conventional
      angiography, CTA, and/or MRA), interventions (self-compression of artery,
      embolization, craniotomy, or a combination of these), results (symptoms resolved,
      improved, or same), and complications (embolic or surgical). All DAVFs were
      classified according to the Cognard classification. RESULTS: There were a total
      of 46 patients with 51 fistulas, of whom 42 patients (46 fistulas) had complete
      follow-up data. Using conventional angiography as the gold standard, CTA had a
      sensitivity of 15.4%, whereas MRA had a sensitivity of 50%. Embolization (either
      single or multiple treatments) was the most common treatment, being done in 36/46
      (78%) fistulas. Presenting symptoms were resolved or improved in 45/46 fistulas
      (97.8%) regardless of treatment or Cognard classification. There were
      complications in 12/46 (26%) patients, most of which were transient and resolved
      without permanent sequelae. CONCLUSIONS: A DAVF is a vascular lesion that is best
      diagnosed with conventional angiography, but can often be found with MRA.
      Treatment with endovascular embolization is effective and has few significant
      complications.

PMID- 19172610
TI  - Lithotripsy for refractory pediatric sialolithiasis.
AB  - Symptomatic salivary stones in the middle or proximal parotid duct have
      traditionally been treated by gland excision, which is associated with a 3% to
      27% risk to the facial nerve in the pediatric population. Minimally invasive
      approaches to the management of salivary duct calculi have been introduced over
      the last several years. Fluoroscopically guided basket retrieval, lithotripsy,
      and intraoral stone removal under general anesthesia have found favor with many
      surgeons. Our patient had extracorporeal lithotripsy to his parotid gland with
      complete disintegration of the stone. He has had no evidence of stone recurrence
      or further bouts of parotitis. Extracorporeal shock wave lithotripsy with or
      without duct dilation is an efficient technique for the therapy of sialolithiasis
      in selected patients, especially patients who are at higher risk from a surgical
      standpoint.

PMID- 19172611
TI  - Outcomes of primary surgical treatment of T1 and T2 carcinomas of the oropharynx.
AB  - OBJECTIVES: Oropharyngeal cancers represent 10%-15% of all head and neck cancers.
      At presentation 60%-70% will have advanced-stage disease with a high incidence of
      neck metastases. Primary treatment employing radiotherapy, with or without
      chemotherapy, is widely prescribed. The aim of this study is to analyze the
      outcome of definitive surgical management of T1-T2 cancers of the oropharynx.
      METHODS: We conducted a retrospective cohort study of patients treated at the
      Sydney Head and Neck Cancer Institute. Patients with previously untreated
      squamous cell carcinoma (SCC) of the oropharynx were included according to the
      TNM stage of the disease as follows: T1 or T2, any N-stage, and M0. All patients
      underwent definitive primary surgical management. Primary analysis endpoints were
      locoregional control rates and disease-specific survival. RESULTS: Ninety-two
      patients were identified, of which 26 were T1 and 66 were T2. Forty-four patients
      had clinical neck disease, and 57 had postoperative radiotherapy. The results
      showed no significant difference between the T1 and T2 groups with respect to
      local control or treatment type; however, advanced-stage neck disease was
      associated with a worse prognosis. The 5-year disease-specific survival was 83%
      and local control rate was 87%. Ultimately, 25 of the 92 patients had treatment
      failure (27%). CONCLUSIONS: Selected patients with early-stage primary cancers of
      the oropharynx may be effectively treated with definitive primary surgery.

PMID- 19172612
TI  - Survival impact of nodal disease in hard palate and maxillary alveolus cancer.
AB  - OBJECTIVE: Evaluate the impact of primary site stage and cervical metastasis on
      the survival of patients with squamous cell carcinoma (SCC) of the hard palate or
      maxillary alveolus. STUDY DESIGN: Cross-sectional population analysis of
      prospectively maintained database. METHODS: Cases of hard palate and maxillary
      alveolus SCC from 1988-2004 were extracted from the Surveillance, Epidemiology,
      and End Results database. Demographic data and extent of disease were extracted
      for each case, and T-stage, and N-stage were computed. Survival differences
      according to T-stage and N-stage were determined with the Kaplan-Meier method and
      the log-rank test. RESULTS: Four hundred eleven cases of maxillary alveolus and
      314 cases of hard palate SCC were identified, for a total of 725 cases (53.9%
      female, mean age: 70.9 years). The prevalence of cervical metastasis was not
      significantly different according to primary site (P = .181); advanced N-stage
      significantly correlated with more advanced T-stage (P < .001). Of the 725 cases,
      4.1% of T1 tumors, 14.9% of T2 tumors, 10.3% of T3 tumors, and 24.7% of T4 tumors
      had cervical nodal metastases. The mean overall survivals were 96.5, 69.1, 67.8,
      and 49.3 months for T1-T4 tumors, respectively (P < .001). With regard to N
      stage, the mean survivals were 73.7, 69.7, 29.8, and 5.5 months for N0-N3
      lesions, respectively (P < .001). Nodal metastasis effect on survival remained
      significant (P < .039) in stratified survival analysis except for T3 lesions (P =
      .205). CONCLUSIONS: Survival in patients with SCC of either the hard palate or
      maxillary alveolus is significantly influenced by T-stage and a nonnegligible
      rate of cervical nodal metastases.

PMID- 19172613
TI  - Comment on M. Guillot-Delost et al. (2008;10:834-846): Clinical-grade preparation
      of human natural regulatory T cells encoding the thymidine kinase suicide gene as
      a safety gene.

PMID- 19172614
TI  - Low-cost dual-action aural foreign-body extractor.
AB  - Adequate visualization, appropriate equipment, a cooperative patient, and a
      skilled physician are keys to successful foreign body removal. The first attempt
      at removal is critical because success rates markedly decrease after the first
      failed attempt.

PMID- 19172615
TI  - Osteoconductivity of strontium-doped bioactive glass particles: a
      histomorphometric study in rats.
AB  - There is accumulating evidence that strontium (Sr)-containing bioceramics have
      positive effects on bone tissue repair. The aims of the present study were to
      evaluate the osteoconductivity of Sr-doped bioactive glass (BG) particles
      implanted in rat tibia bone marrow, and characterize the neoformed bone tissue by
      SEM-energy-dispersive X-ray microanalysis. Melt-derived BGs were prepared from a
      base 45S5 BG. Sr-doped glass (45S5.6Sr) was prepared using 6 wt % SrO as a
      substitute for the CaO. Histological analysis using undecalcified sections showed
      that new lamellar bone had formed along the surface of both 45S5 and 45S5.6Sr BG
      particles within 4 weeks. To evaluate osteoconductivity, affinity indices were
      calculated. At 30 days after implantation, 45S5 and 45S5.6Sr BGs had almost
      identical affinity indices (88% +/- 7% and 87% +/- 9%; p > 0.05). Strontium was
      not detected in the neoformed bone tissue surrounding 45S5.6Sr BG particles.
      These results indicate that 45S5.6Sr BG particles are osteoconductive when
      implanted inside the intramedullary canal of rat tibiae, and no alterations in
      bone mineralization, in terms of Ca/P ratio, were observed in the neoformed bone
      tissue around 45S5.6Sr BG particles.

PMID- 19172616
TI  - A survey of Louisiana hospital ethics committees.
AB  - OBJECTIVES: To obtain a picture of hospital ethics committees (HECs) in the State
      of Louisiana. Compare results to other published studies. Gauge interest and
      participation in HECs by otolaryngologists. STUDY DESIGN: Mail in questionnaire
      to all hospitals in Louisiana. Minisurvey distributed to randomly selected
      otolaryngologists. METHODS: A questionnaire was mailed to the 194 hospitals
      identified by the Louisiana State Hospital Association. Questions included the
      presence and description of HECs plus the demographic data for the hospitals.
      RESULTS: Eighty-eight hospitals returned the survey. A HEC was present in 69.
      Membership was most often multidisciplinary. The annual growth rate ranged from
      1.7% to 6%-8%. Teaching hospitals and larger hospitals tended to have a higher
      frequency rate of HECs. Like most US HECs, this state's committee primary
      functions included case consultation, education, and policy review. About 30% of
      otolaryngologists surveyed had some experience with a HEC. CONCLUSIONS:
      Louisiana's HEC construction and function appear similar to those committees
      found in other US hospitals. Membership is multidisciplinary. The three major
      functions are education, policy development and case consultation. Larger
      institutions tend to have a higher frequency of HECs. The growth rate of HECs
      increased in the early 1990s. As the ethical issues in contemporary medicine
      become more complex, especially with technological advances, HECs can anticipate
      constant new challenges. Future direction may focus on the evaluation of how well
      HECs function and on how improvements can be made.

PMID- 19172617
TI  - Bioactivating electrically conducting polypyrrole with fibronectin and bovine
      serum albumin.
AB  - Electrically conducting polypyrrole (PPy) and its composite materials are useful
      in interfacing electrical components and cells or living tissue. In recent years,
      significant efforts have been made to bioactivate PPy by incorporating
      biomolecules. The main objective of this work was to chemically bioactivate PPy
      particules by incorporating fibronectin (FN) and bovine serum albumin (BSA).
      Modified PPy particles were synthesized through a water-in-oil emulsion
      polymerization. XPS and FTIR confirmed the presence of biomolecules on the PPy
      particles, and the surface morphology was observed by SEM. A four-point probe was
      used to measure the conductivity of the newly synthesized PPy particles, which
      was in the range of 10(-1) S cm(-1). Conductive biodegradable membranes were
      prepared with 5 and 10% (wt/wt) PPy to poly(L,L-lactide) (PPy/PLLA). The contact
      angles of each synthesized membrane were approximately 75 degrees , supporting
      their usefulness for cell culture. The cultured human skin fibroblasts
      demonstrated normal morphology and significantly higher adhesion and spreading on
      the PPy/PLLA approximately FN membrane than on the unmodified PPy/PLLA membrane.
      On the other hand, the PPy/PLLA approximately BSA membranes showed decreased cell
      adhesion. Bioactivated PPy may be useful in tissue engineering to fabricate
      conducting biodegradable scaffolds with either improved or reduced cell adhesion
      properties for various cell culture and in vivo applications.

PMID- 19172618
TI  - Evaluation of clinical biomaterial surface effects on T lymphocyte activation.
AB  - Previous in vitro studies in our laboratory have shown that lymphocytes can
      influence macrophage adhesion and fusion on biomaterial surfaces. However, few
      studies have evaluated how material adherent macrophages can influence lymphocyte
      behavior, specifically T cells. In this study, we cultured human peripheral blood
      mononuclear cells from healthy donors on three synthetic nonbiodegradable
      biomedical polymers: elasthane 80A (PEU), silicone rubber (SR), or polyethylene
      terephthalate (PET) and tissue culture polystyrene (TCPS). Upregulation of T cell
      surface activation markers (CD69 and CD25), lymphocyte proliferation, and
      interleukin-2 (IL-2) and interferon-gamma (IFNgamma) concentrations were
      evaluated by flow cytometry, carboxy-fluorescein diacetate, succinimydyl ester
      (CFSE) incorporation, and multiplex cytokine immunoassay, respectively, to assess
      T cell activation. Following 3 and 7 days of culture, CD4+ helper T cells from
      cultures of any of the material groups did not express the activation markers
      CD69 and CD25 and lymphocyte proliferation was not present. IL-2 and IFNgamma
      levels were produced, but dependent on donor. These data indicate that T cells
      are not activated in response to clinically relevant synthetic biomaterials. The
      data also suggest that lymphocyte subsets exclusive of T cells are the source of
      the lymphokines, IL-2 and IFN-gamma, in certain donors.

PMID- 19172619
TI  - In vitro cartilage formation using TGF-beta-immobilized magnetic beads and
      mesenchymal stem cell-magnetic bead complexes under magnetic field conditions.
AB  - We evaluated the efficacy of transforming growth factor (TGF)-beta-immobilized
      magnetic beads for chondrogenesis in vitro using a mesenchymal stem cell (MSC)
      delivery system and an external magnetic force (EMF). MSCs isolated from the bone
      marrow of Sprague Dawley rats were mixed with carboxyl group-combined magnetic
      beads (Ferri Sphere 100C) coated with anti-rat CD44 mouse monoclonal antibodies.
      TGF-beta3 (10 and 1 ng/mL) was attached magnetically to such other Ferri Sphere
      100C beads via an amide bond formed between a primary amino group on the TGF
      beta3 and the carboxyl groups on the surface of the beads. MSC-magnetic bead
      complexes were centrifuged to form a pellet and cultured in chondrogenic
      differentiation medium (CDM) supplemented with either 10 or 1 ng/mL TGF-beta
      immobilized magnetic beads (10 or 1 ng/mL TGF-beta-immobilized magnetic bead
      groups) or in CDM supplemented with 1 or 10 ng/mL TGF-beta (1 or 10 ng/mL TGF
      beta group). TGF-beta-immobilized magnetic beads were gathered effectively under
      an EMF. Chondrogenesis was achieved from the MSC-magnetic bead complexes in the
      presence of 1 ng/mL TGF-beta-immobilized magnetic beads.

PMID- 19172620
TI  - Response of rat osteoblasts to polycaprolactone/chitosan blend porous scaffolds.
AB  - Novel porous polycaprolactone/chitosan blend scaffolds were fabricated via a
      particle-leaching technique using hexafluoro-2-propanol as a shared solvent and
      salt particles as porogen. By selecting optimized processing conditions, numerous
      blend scaffolds were already built with well-controlled porous structures and
      approximately similar pore parameters. The interactions between these scaffolds
      and the rat osteoblasts were further investigated by measuring the adhesion,
      proliferation, and morphologies of cells as well as the corresponding alkaline
      phosphatase activity during various culture periods in vitro. Data collected from
      different measurements reflected that by incorporating an appropriate amount of
      chitosan component, the resultant blend scaffolds could improve the adhesion and
      growth of osteoblasts and exert a significant impact on the osteoblastic
      phenotype.

PMID- 19172621
TI  - Bisphosphonate-related osteonecrosis of the jaw and its associated risk factors:
      a Belgian case series.
AB  - OBJECTIVES: Bisphosphonate-related osteonecrosis of the jaw (BROJ) is a serious
      oral complication of bisphosphonate (BP) treatment involving the exposure of
      necrotic maxillary or mandibular bone. Our purpose is to describe the clinical
      presentation of 34 cases of BROJ and to identify potential risk factors. STUDY
      DESIGN: A retrospective study was performed in four Belgian institutions.
      METHODS: Complete medical histories were recorded and analyzed. These data
      include age, gender, initial disease requiring BP, type and duration of BP
      treatment, symptomatology and location of BROJ, prior dental procedures,
      treatment of the BROJ and treatment outcome, and radiographic, histological, and
      microbiological data. RESULTS: Bisphosphonates (BP) were used in the management
      of disseminated cancers in 30 patients (88.5% of total studied), while four
      patients received BP due to osteoporosis (11.5%). The most frequently used BP was
      zoledronic acid in 29 patients (83%). Microbiological data obtained in 25
      patients demonstrated that 72% of these patients were infected or colonized by an
      actinomyces. Eight of the 14 patients (57%) who received only medical treatment
      were cured. Of the 20 patients who underwent surgical treatments, only four were
      completely cured (20%). BROJ lesions smaller than 1 cm are associated with better
      prognosis in terms of treatment outcomes (P = .0009). Local treatments combined
      with long-term antibiotics are also correlated with better prognosis (P = .02).
      CONCLUSIONS: Lesions smaller than 1 cm and lesions that were subject to medical
      treatments are associated with a better outcome. Surgical treatments appear to be
      non-beneficial for BROJ.

PMID- 19172622
TI  - Screening biomaterials for functional complement activation in serum.
AB  - Complement plays an important role in the immune attack against invading
      microorganisms. However, blood-contacting medical device biomaterials lacking
      specific complement inhibitors, with free hydroxyl and/or amino groups, or with
      absorbed antibodies, may inappropriately activate complement. Inappropriate
      activation by either the antibody-mediated classical or the antibody-independent
      alternative pathway may have well-known acute or poorly understood chronic
      effects on the host or device. This article describes methods for screening
      biomaterials for functional whole complement activation using normal human serum,
      or specifically for alternative pathway activation using C4-deficient guinea pig
      serum, or for classical pathway activation using both sera in combination.
      Detailed protocols are available as standard methodologies from the American
      Society for Testing and Materials (ASTM F1984, ASTM F2065, and ASTM F2567).
      Results obtained with these functional tests are confirmed by detection of
      classical and alternative pathway-specific markers C4d and Bb, respectively.
      These methods demonstrate dose and time-course activation of complement to beaded
      agarose, cellulose acetate, and purified alginate as examples of biomaterials.
      Significant difference in a functional endpoint denoting specific complement
      pathways is an appropriate screening method for complement activation by medical
      device biomaterials which might result in adverse events when the device is
      implanted or contacts human blood.

PMID- 19172623
TI  - Advanced time-series analysis of MEG data as a method to explore olfactory
      function in healthy controls and Parkinson's disease patients.
AB  - OBJECTIVES: To determine whether time-series analysis of magnetoencephalography
      (MEG) data is a suitable method to study brain activity related to olfactory
      information processing, and to detect differences in odor-induced brain activity
      between patients with Parkinson's disease (PD) and controls. METHODS: Whole head
      151-channel MEG recordings were obtained in 21 controls and 20 patients with PD
      during a 10-min olfactory stimulus paradigm, consisting of 10 alternating rest
      stimulus cycles (30 s each), using phenylethyl alcohol administered by means of a
      Burghart olfactometer. Relative spectral power and synchronization likelihood
      (SL; an unbiased measure of functional connectivity) were calculated for delta,
      theta, alpha1, alpha2, beta, and gamma frequency bands. RESULTS: In controls,
      olfactory stimulation produced an increase in theta power and a decrease in beta
      power. In patients with PD, there was a decrease in alpha1 power. No significant
      interaction between group and condition was found for spectral power. SL analysis
      revealed a significantly different response to olfactory stimulation in patients
      with PD compared to controls. In controls, the odor stimulus induced a decrease
      in local beta band SL. The response in patients with PD involved a decrease in
      intrahemispheric alpha2 band SL. CONCLUSION: This is the first study to show that
      time-series analysis of MEG data, including spectral power and SL, can be used to
      detect odor-induced changes in brain activity. In addition, differences in odor
      induced brain activity were found between patients with PD and controls using
      analysis of SL, but not of spectral power.

PMID- 19172625
TI  - Syllable congruency and word frequency effects on brain activation.
AB  - This article investigates the neural representation of the processes involved in
      recognizing multisyllabic words in Spanish asking whether lexical and sublexical
      processes are reflected in a different neuronal activation pattern. High and low
      frequency words were presented for lexical decision in two different colors. In
      the congruent condition the color boundaries matched the limit of the first
      syllable, whereas in the incongruent condition color boundaries and syllable
      boundaries did not match. The results revealed robust and dissociable brain
      activations for lexical frequency and syllable-color congruency, but no
      interaction between the two. We interpreted the greater activation for low
      relative to high frequency words in the left pre/SMA region, and in the
      insula/inferior frontal cortex bilaterally to reflect a differential recruitment
      of lexico-phonological and/or semantic processes. In contrast, we considered two
      interpretations for the greater deactivation in the precuneus for both lexical
      frequency and syllable-color congruency words, and in the thalami and a frontal
      area for syllable-color congruency words only. The deactivations may reflect the
      differential engagement of semantic processing or may result from the
      differential allocation of attentional resources. Importantly, while a
      differential deactivation pattern was observed in the precuneus region for
      lexicality and syllable-color congruency, BOLD deconvolution revealed a
      remarkable difference in timing of the two effects with a much earlier
      deactivation peak for the syllable-color congruency factor. Thus, effects of
      lexical frequency and syllable-color congruency on brain activation show an
      important dissociation between lexical and sublexical processes during visual
      word recognition of multisyllabic words.

PMID- 19172624
TI  - Functional connectivity between the thalamus and visual cortex under eyes closed
      and eyes open conditions: a resting-state fMRI study.
AB  - The thalamus and visual cortex are two key components associated with the alpha
      power of electroencephalography. However, their functional relationship remains
      to be elucidated. Here, we employ resting-state functional MRI to investigate the
      temporal correlations of spontaneous fluctuations between the thalamus [the whole
      thalamus and its three largest nuclei (bilateral mediodorsal, ventrolateral and
      pulvinar nuclei)] and visual cortex under both eyes open and eyes closed
      conditions. The whole thalamus show negative correlations with the visual cortex
      and positive correlations with its contralateral counterpart in eyes closed
      condition, but which are significantly decreased in eyes open condition,
      consistent with previous findings of electroencephalography desynchronization
      during eyes open resting state. Furthermore, we find that bilateral thalamic
      mediodorsal nuclei and bilateral ventrolateral nuclei have remarkably similar
      connectivity maps, and resemble to those of the whole thalamus, suggesting their
      crucial contributions to the thalamus-visual correlations. The bilateral pulvinar
      nuclei are found to show distinct functional connectivity patterns, compatible
      with previous findings of the asymmetry of anatomical and functional organization
      in the nuclei. Our data provides evidence for the associations of intrinsic
      spontaneous neuronal activity between the thalamus and visual cortex under
      different resting conditions, which might have implications on the understanding
      of the generation and modulation of the alpha rhythm.

PMID- 19172626
TI  - Microdebrider-assisted versus radiofrequency-assisted inferior turbinoplasty.
AB  - OBJECTIVES: The study aimed to evaluate the long-term efficacy of microdebrider
      assisted inferior turbinoplasty (MAIT) compared to radiofrequency-assisted
      inferior turbinoplasty (RAIT) for hypertrophic inferior turbinates. STUDY DESIGN:
      Surgical outcomes were evaluated using the visual analogue scale, anterior
      rhinomanometry, and saccharin test results. METHODS: From January 2001 to
      December 2006 inclusively, 120 patients with persistent allergic rhinitis,
      chronic nasal obstruction, and hypertrophic inferior turbinates were enrolled in
      this study, randomly classified, and underwent either MAIT (n = 60) or RAIT. Ten
      patients who did not have any nasal discomfort served as normal controls.
      Assessments (visual analogue scale, anterior rhinomanometry, and saccharin test)
      were conducted prior to surgery and 6 months, 1, 2, and 3 years subsequent to
      surgery. RESULTS: Compared to preoperative values, the symptom scores (nasal
      obstruction, sneezing, rhinorrhea, and snoring), mean total nasal resistance, and
      mean saccharin transit time all improved significantly at 6 months, 1, 2, and 3
      years after surgery in MAIT group (P < .05 for all). The same holds true for the
      RAIT group from 6 months up to 1 year (P < .05 for all), but no improvements from
      2 to 3 years after were noted. The parameters between the two groups did not
      significantly differ 6 months after surgery, but was noted after 1 to 3 years (P
      < .05 for all). CONCLUSION: MAIT is more effective than RAIT at relieving nasal
      symptoms and decreasing total nasal resistance and saccharin transit time 1 to 3
      years postoperatively in patients with persistent allergic rhinitis and who have
      substantial nasal obstruction.

PMID- 19172627
TI  - Randomized, double blind, placebo controlled trial on the safety and efficacy of
      continuous intratympanic dexamethasone delivered via a round window catheter for
      severe to profound sudden idiopathic sensorineural hearing loss after failure of
      systemic therapy.
AB  - OBJECTIVES: To study the safety and efficacy of continuous intratympanic
      dexamethasone-phosphate (Dex-P) for severe to profound sudden idiopathic
      sensorineural hearing (ISSHL) or sudden idiopathic anacusis after failure of
      systemic therapy. STUDY DESIGN: Randomized, double-blind, placebo controlled
      multicenter trial. METHODS: Patients with ISSHL and insufficient recovery (mean
      4PTA = 97 dB HL) after systemic high dose glucocorticoid therapy received either
      Dex-P (4 mg/ml) or placebo (NaCl 0.9%) continuously applied for 14 days into the
      round window niche via a temporarily implanted catheter. For ethical reasons,
      intratympanic treatment was continued with Dex-P in all patients for another 14
      days after the placebo-controlled study period. According to a two-step adaptive
      study design an interim analysis was performed after inclusion of 23 patients.
      RESULTS: Intention-to-treat analysis for the primary outcome criterion (4PTA: 0.5
      3 kHz) during the placebo controlled study period (14 days) showed an average
      hearing improvement in the treatment group of 13.9 dB (SD: 21.3) and in the
      placebo group of 5.4 dB (SD: 10.4). This difference in hearing improvement
      between the two groups (mean: 8.4 dB, SD: 17.0, 95% CI: -7.1-24.1) was
      statistically not significant (p = .26). Of the secondary outcome parameters, the
      largest benefit of local salvage therapy was found for maximum speech
      discrimination with an improvement of 24.4% (SD: 32.0) in the treatment and 4.5%
      (SD: 7.6) in the placebo group (p = 0.07). After a 3 month follow-up period (i.e.
      after all patients received intratympanic Dex-P) hearing improvement in the two
      groups was very similar. No serious adverse events were observed. Sample size
      calculation after the interim analysis resulted in stopping of the trial.
      CONCLUSIONS: The tendency toward better hearing improvement in the treatment
      group, the rather conservative inclusion criteria, the limited placebo-controlled
      observation period and the absence of serious adverse events supports further
      investigation local inner ear drug delivery as a first or second line treatment
      option for ISSHL.

PMID- 19172628
TI  - The laryngeal chemoreflex: an evaluation of the normoxic response.
AB  - OBJECTIVES: The laryngeal chemoreflex is a reflexive central apnea, bradycardia,
      and cardiovascular collapse that occurs in young, maturing mammals in response to
      exposure of the laryngeal mucosa to acidic and/or organic stimuli. The severity
      of the laryngeal chemoreflex varies within a species from one animal to another,
      and in some animals, the response can be fatal. This study seeks to identify
      those factors that contribute to fatal laryngeal chemoreflex responses when the
      larynx is stimulated under normoxic conditions, and to define how the normoxic
      response differs from the hypoxic laryngeal chemoreflex response. STUDY DESIGN:
      This is a prospective study evaluating the response to laryngeal stimulation of
      80 newborn piglets. METHODS: The laryngeal chemoreflex response was elicited from
      67 piglets under normoxic conditions. The data were collected from a combination
      of three separate experimental protocols, each of which included inducing the
      laryngeal chemoreflex under normoxic conditions as the first step. The
      physiologic response was recorded with a combination of arterial blood gas, pulse
      oximetry, blood pressure, and continuous cardiac monitoring. RESULTS: Resumption
      of respirations occurred when the pCO(2) rose by a mean of 8.34 (Standard
      Deviation [SD] = 4.8) mmHg, regardless of response severity (ANOVA, P > .05).
      Moderate (requiring supplemental O(2) for recovery) and profound (fatal)
      responders had a significantly higher prestimulation pCO(2) (95% confidence
      interval [CI] 39.8-44.8 mmHg and 40.5-46.4 mmHg, respectively) than did mild
      (recovery without assistance) responders (95% CI 36.8-40.8 mmHg, ANOVA, P < .05).
      Baseline pH was statistically significantly different as a function of response
      severity (95% CI profound: 7.29-7.37, moderate: 7.33-7.38, and mild 7.36-7.39, P
      < .05). CONCLUSIONS: Accumulation of arterial CO(2) is associated with resumption
      of respirations during the normoxic laryngeal chemoreflex. The combination of an
      elevated prestimulation pCO(2) and a low prestimulation pH predicts a profound
      laryngeal chemoreflex response under normoxic conditions.

PMID- 19172629
TI  - Coblation removal of large suprastomal tracheal granulomas.

PMID- 19172630
TI  - Bile acids identified in middle ear effusions of children with otitis media with
      effusion.
AB  - OBJECTIVES/HYPOTHESIS: Several studies have shown the presence of pepsin in the
      middle ear effusions of children with otitis media with effusion (OME). When
      gastric reflux is the cause, other noxious reflux products might be present. We
      therefore investigated the presence of bile acids in the middle ear effusions of
      children with OME. STUDY DESIGN: We evaluated 38 children (63 samples of middle
      ear secretions (ME samples)) in a prospective study at a tertiary care children's
      hospital. METHODS: ME samples were collected from children with OME during
      ventilation tube insertion. Most ME samples were diluted with albumin. The
      presence of bile acids was measured with the 3alpha-hydroxy steroid dehydrogenase
      enzymatic method. A ME sample was considered positive when it contained at least
      5 mumol/l bile acids, independent of dilution. Blood samples were taken
      simultaneously as a reference to determine bile acids serum levels. RESULTS: We
      found bile acids in 32 % (20/63) of all ME samples and in 42% (16/38) of all
      children. Bile acids concentrations of 12 well-soluble ME samples ranged from 5.9
      40.9 mumol/L and were 3.1-19.7 times higher than the serum concentrations. In 4
      of the corresponding serums, no bile acids were measurable at all. CONCLUSIONS:
      Bile acids are present in a number of the ME samples of children with OME.
      Because of dilution, it is possible that more ears contain bile acids. Bile acids
      are known to be noxious to mucosal cells at a higher (pH) than pepsin and,
      therefore, might play a role in the pathology of OME.

PMID- 19172631
TI  - A method for accurate group difference detection by constraining the mixing
      coefficients in an ICA framework.
AB  - Independent component analysis (ICA) is a promising method that is increasingly
      used to analyze brain imaging data such as functional magnetic resonance imaging
      (fMRI), structural MRI, and electroencephalography and has also proved useful for
      group comparison, e.g., differentiating healthy controls from patients. An
      advantage of ICA is its ability to identify components that are mixed in an
      unknown manner. However, ICA is not necessarily robust and optimal in identifying
      between-group effects, especially in highly noisy situations. Here, we propose a
      modified ICA framework for multigroup data analysis that incorporates prior
      information regarding group membership as a constraint into the mixing
      coefficients. Our approach, called coefficient-constrained ICA (CC-ICA),
      prioritizes identification of components that show a significant group
      difference. The performance of CC-ICA via synthetic and hybrid data simulations
      is evaluated under different hypothesis testing assumptions and signal to noise
      ratios (SNRs). Group analysis is also conducted on real multitask fMRI data.
      Results show that CC-ICA improves the estimation accuracy of the independent
      components greatly, especially those that have different patterns for different
      groups (e.g., patients vs. controls); In addition, it enhances the data
      extraction sensitivity to group differences by ranking components with P value or
      J-divergence more consistently with the ground truth. The proposed algorithm
      performs quite well for both group-difference detection and multitask fMRI data
      fusion, which may prove especially important for the identification of relevant
      disease biomarkers.

PMID- 19172632
TI  - Spatiotemporal mapping of sex differences during attentional processing.
AB  - Functional neuroimaging studies have increasingly aimed at approximating neural
      substrates of human cognitive sex differences elicited by visuospatial challenge.
      It has been suggested that females and males use different behaviorally relevant
      neurocognitive strategies. In females, greater right prefrontal cortex activation
      has been found in several studies. The spatiotemporal dynamics of neural events
      associated with these sex differences is still unclear. We studied 22 female and
      22 male participants matched for age, education, and nicotine with 29-channel
      electroencephalogram recorded under a visual selective attention paradigm, the
      Attention Network Test. Visual event-related potentials (ERP) were
      topographically analyzed and neuroelectric sources were estimated. In absence of
      behavioral differences, ERP analysis revealed a novel frontal-occipital second
      peak of visual N100 that was significantly increased in females relative to
      males. Further, in females exclusively, a corresponding central ERP component at
      around 220 ms was found; here, a strong correlation between stimulus salience and
      sex difference of the central ERP component amplitude was observed. Subsequent
      source analysis revealed increased cortical current densities in right rostral
      prefrontal (BA 10) and occipital cortex (BA 19) in female subjects. This is the
      first study to report on a tripartite association between sex differences in
      ERPs, visual stimulus salience, and right prefrontal cortex activation during
      attentional processing.

PMID- 19172633
TI  - ICA decomposition of EEG signal for fMRI processing in epilepsy.
AB  - In this study, we introduce a new approach to process simultaneous
      Electroencephalography and functional Magnetic Resonance Imaging (EEG-fMRI) data
      in epilepsy. The method is based on the decomposition of the EEG signal using
      independent component analysis (ICA) and the usage of the relevant components'
      time courses to define the event related model necessary to find the regions
      exhibiting fMRI signal changes related to interictal activity. This approach
      achieves a natural data-driven differentiation of the role of distinct types of
      interictal activity with different amplitudes and durations in the epileptogenic
      process. Agreement between the conventional method and this new approach was
      obtained in 6 out of 9 patients that had interictal activity inside the scanner.
      In all cases, the maximum Z-score was greater in the fMRI studies based on ICA
      component method and the extent of activation was increased in 5 out of the 6
      cases in which overlap was found. Furthermore, the three cases where an agreement
      was not found were those in which no significant activation was found at all
      using the conventional approach.

PMID- 19172634
TI  - Effects of sprayer configuration on efficacy for the control of scab on crabapple
      using electron beam analysis.
AB  - Foliar diseases like apple scab result in significant economic losses to growers
      each year. Assessment in past studies involved only macroscopic disease ratings.
      More complete knowledge of the fate and behavior of fungicide has been needed to
      reduce pesticide use with less off-target contamination. Field studies were
      conducted in a production nursery for over 4 years. A moderately susceptible
      cultivar of ornamental crabapple, Malus spp. cv "Candied Apple", was sprayed with
      a fungicide using two sprayer/nozzle configurations. The fungicide used in this
      study was Mankocide, combination of Cu(OH)2 and mancozeb that permitted electron
      beam analysis (EBA) identification based on the presence of Cu, MN and Zn in the
      molecule and formulation. EBA was conducted using a cold field emission scanning
      electron microscopy and energy dispersive x-ray microanalyzer. Fresh leaf samples
      were placed on sticky stubs after each fungicide treatment. The presence or
      absence of fungal conidia and fungicide residue were measured. EBA permitted
      direct visualization and identification of the pathogens, morphologically, and
      chemical characterization of fungicide present. EBA was useful to quantify
      disease control related to fungicide coverage, sprayer configuration and
      treatment efficacy.

PMID- 19172635
TI  - Outcome measures used in forensic mental health research: a structured review.
AB  - BACKGROUND: The evidence base for forensic mental health (FMH) services has been
      developing since the late 1990s. Are outcome measures sound enough for the
      evaluation tasks? AIMS: To identify, from published literature, outcome measures
      used in FMH research and, where feasible, assess their quality. METHOD: A
      structured review was undertaken of trials and intervention studies published
      between 1990 and 2006. Details of outcome variables and measures were abstracted.
      Evidence regarding most frequently occurring outcome measures was assessed.
      RESULTS: Four hundred and fifty different instruments were used to assess
      outcomes, incorporating 1038 distinct variables. Very little evidence could be
      found to support the measurement properties of commonly used instruments.
      CONCLUSIONS: and implications for practice There is little consistency in the use
      of outcome measure in FMH research. Effort is required to reach consensus on
      validated outcome measures in this field in order to better inform practice.

PMID- 19172636
TI  - The future is offender health: evidencing mainstream health services throughout
      the offender pathway.

PMID- 19172637
TI  - Developing an attitude towards bullying scale for prisoners: structural analyses
      across adult men, young adults and women prisoners.
AB  - BACKGROUND: Few studies have attempted to explore attitudes towards bullying
      among prisoners, despite acknowledgement that attitudes may play an important
      role. AIM: To evaluate the structure of a new attitudinal scale, the Prison
      Bullying Scale (PBS), with adult men and women in prison and with young male
      prisoners. HYPOTHESES: That attitudes would be represented as a multidimensional
      construct and that the PBS structure would be replicated across confirmatory
      samples. METHOD: The PBS was developed and confirmed across four independent
      studies using item parceling and confirmatory factor analysis: Study I comprised
      412 adult male prisoners; Study II, 306 adult male prisoners; Study III, 171 male
      young offenders; and Study IV, 148 adult women prisoners. RESULTS: Attitudes were
      represented as a multidimensional construct comprising seven core factors. The
      exploratory analysis was confirmed in adult male samples, with some confirmation
      among young offenders and adult women. The fit for young offenders was adequate
      and improved by factor covariance. The fit for women was the poorest overall.
      CONCLUSION: The study notes the importance of developing ecologically valid
      measures and statistically testing these measures prior to their clinical or
      research use. IMPLICATIONS: The development of the PBS holds value both as an
      assessment and as a research measure and remains the only ecologically validated
      measure in existence to assess prisoner attitudes towards bullying.

PMID- 19172638
TI  - A qualitative study exploring the life-course experiences of young offenders with
      symptoms and signs of ADHD who were detained in a residential care setting.
AB  - BACKGROUND: An association between attention-deficit/hyperactivity disorder
      (ADHD) and offending is increasingly being recognised among youths in the
      criminal justice system, but is poorly understood. METHODS: Using the qualitative
      methodology of Interpretive Phenomenological Analysis, we explored the self
      reported life-course experiences of five adolescents in a young offenders' secure
      unit; all had been rated by teachers on Conner's scale as having ADHD, although
      only one had received a clinical diagnosis. RESULTS: Three master themes were
      identified: loss, a search for belonging and responses to confinement. The themes
      suggest that both the ADHD and the offending behaviour of these young men need to
      be understood in the context of losses that they have suffered and their
      responses to these losses. They showed a preoccupation with family matters and a
      desperate wish to find a way to belong; they almost seemed to welcome some
      aspects of their confinement. CONCLUSION: These themes suggest that 'being held'
      may, to some extent, fulfil a self-identified need for belonging and reattachment
      after major losses. Therapeutic interventions may need to take account of the
      possibility that this confinement may also validate for these young men a
      tendency to attribute the course of their lives to external factors.

PMID- 19172639
TI  - The development of a specialist hostel for the community management of
      personality disordered offenders.
AB  - BACKGROUND: Since the late 1990s, in England and in Wales, there has been
      increasing interest in the particular challenges of managing offenders with
      personality disorder (PD). In 1999, a specialist hostel, managed by the probation
      service but with a high level of forensic mental health service input, was opened
      to high-risk PD offenders. AIMS: To describe the first 93 high-risk residents
      with PD who were completing sentences under life licence, parole or probation,
      and their outcome. METHODS: We investigated the nature of the offences residents
      had previously committed, their psychological profile in terms of personality
      patterns on the Millon Clinical Multiaxial Inventory (MCMI-III) and the
      Psychopathy Checklist-Revised (PCL-R), as well as staff commentary on their
      progress, to establish whether these factors related to outcome in terms of
      completion of stay in the hostel or premature discharge. Curfew failures and
      rearrest rates were also measured. RESULTS: Of the 80 men who completed their
      residency within the two years of the study, the majority (50) left the hostel
      for positive reasons under mutual agreement. One-fifth were rearrested while
      resident, which is a lower rate than would be expected for such a group of
      offenders. PCL-R scores were predictive of outcome, but so was previous offending
      history. Self-defeating traits on the MCMI-III and negative comments written by
      hostel staff were also associated with failure. CONCLUSIONS: The hostel
      development demonstrated that probation and health services can work together to
      manage violent offenders with high levels of psychological dysfunction, and the
      evaluation provided some indications of how such arrangements might be enhanced.

PMID- 19172640
TI  - A voxel-based morphometric MRI study in men with borderline personality disorder:
      preliminary findings.
AB  - OBJECTIVE: There is increasing evidence for subtle changes in brain morphology
      and function in patients with borderline personality disorder (BPD). Structural
      brain imaging studies show lower volume in frontal, temporal and parietal brain
      regions than in healthy controls. The aim of our preliminary study of men with
      BPD was to investigate structural brain changes and their relationship with a
      measure of impulsivity. METHODS: We examined seven male patients with BPD and six
      control men using voxel-based morphometry. Analysis of covariance was carried out
      to assess regionally specific differences in grey and white matter (WM) volumes.
      Correlations between trait impulsivity as measured using the Impulsiveness
      Venturesomeness-Empathy scale and brain volumes were studied. RESULTS: Compared
      with healthy men, men with BPD had similar WM volumes but smaller grey matter
      (GM) volumes in frontal, temporal and parietal cortices. The latter were
      negatively correlated with trait impulsivity. CONCLUSIONS: Our findings fit with
      previous reports of smaller regional GM volumes reported in women with BPD, and
      suggest that in men there may be an association between smaller GM volumes and
      impulsivity.

PMID- 19172642
TI  - A multiparametric evaluation of regional brain damage in patients with primary
      progressive multiple sclerosis.
AB  - The purpose of this study is to define the topographical distribution of gray
      matter (GM) and white matter (WM) damage in patients with primary progressive
      multiple sclerosis (PPMS), using a multiparametric MR-based approach. Using a 3
      Tesla scanner, dual-echo, 3D fast-field echo (FFE), and diffusion tensor (DT) MRI
      scans were acquired from 18 PPMS patients and 17 matched healthy volunteers. An
      optimized voxel-based (VB) analysis was used to investigate the patterns of
      regional GM density changes and to quantify GM and WM diffusivity alterations of
      the entire brain. In PPMS patients, GM atrophy was found in the thalami and the
      right insula, while mean diffusivity (MD) changes involved several cortical
      subcortical structures in all cerebral lobes and the cerebellum. An overlap
      between decreased WM fractional anisotropy (FA) and increased WM MD was found in
      the corpus callosum, the cingulate gyrus, the left short temporal fibers, the
      right short frontal fibers, the optic radiations, and the middle cerebellar
      peduncles. Selective MD increase, not associated with FA decrease, was found in
      the internal capsules, the corticospinal tracts, the superior longitudinal
      fasciculi, the fronto-occipital fasciculi, and the right cerebral peduncle. A
      discrepancy was found between regional WM diffusivity changes and focal lesions
      because several areas had DT MRI abnormalities but did not harbor T2-visible
      lesions. Our study allowed to detect tissue damage in brain areas associated with
      motor and cognitive functions, which are known to be impaired in PPMS patients.
      Combining regional measures derived from different MR modalities may be a
      valuable tool to improve our understanding of PPMS pathophysiology.

PMID- 19172643
TI  - The free choice whether or not to respond after stimulus presentation.
AB  - The concept of 'willed' actions has attracted attention during the last few
      years. Free choices have been associated with activations on the medial frontal
      surface, the dorsolateral prefrontal cortex and the parietal lobe. Self-paced
      movements and free selection between various motor responses were typically used
      to investigate voluntary behavior. The aim of the present study was to determine
      neural correlates of voluntary motor responses and the voluntary inhibition of
      motor responses in a group of healthy subjects. Hence, a go/nogo/voluntary
      selection paradigm was used. In the voluntary selection condition subjects
      decided freely whether or not to respond with a button press after stimulus
      presentation. Functional MRI data and event-related potentials were acquired
      simultaneously in order to reliably investigate spatial and temporal
      characteristics of these responses. The results showed decision-related enhanced
      neural responses predominantly in the medial frontal gyrus/supplementary motor
      area, lateral frontal brain regions and the inferior parietal gyrus. Additional
      activations associated with voluntary movements were detected in the frontal eye
      field as well as brain regions directly linked to motor responses (e.g.
      somatosensory cortical areas). Altogether, decision processes were shown to be
      relatively independent of the kind of response chosen.

PMID- 19172644
TI  - Fact learning in complex arithmetic and figural-spatial tasks: the role of the
      angular gyrus and its relation to mathematical competence.
AB  - Neuroimaging studies have revealed a strong link between mental calculation and
      the angular gyrus (AG) which has been interpreted to reflect arithmetic fact
      retrieval. Moreover, a stronger AG activation in individuals with higher
      mathematical competence has been reported. The present fMRI study investigates
      the specificity of the AG for arithmetic fact learning and the interplay between
      training and mathematical competence on brain activation. Adults of lower and
      higher mathematical competence underwent a five-day training on sets of complex
      multiplication and figural-spatial problems. In the following fMRI test session,
      trained and untrained problems were presented. Similar training effects were
      observed in both problem types, consisting of AG activation increases bilaterally
      and wide-spread activation decreases in frontal and parietal regions. This
      finding indicates that the AG is not specifically involved in the learning of
      arithmetic facts. Competence-related differences in the AG only emerged in
      untrained but not in trained multiplication problems. The relation between AG
      activation and mathematical competence in arithmetic problem solving therefore
      seems to be due to differences in arithmetic fact retrieval which can be
      attenuated through training.

PMID- 19172645
TI  - Separating function from structure in perfusion imaging of the aging brain.
AB  - The accuracy of cerebral blood flow (CBF) imaging in humans has been impeded by
      the partial volume effects (PVE), which are a consequence of the limited spatial
      resolution. Because of brain atrophy, PVE can be particularly problematic in
      imaging the elderly and can considerably overestimate the CBF difference with the
      young. The primary goal of this study was to separate the structural decline from
      the true CBF reduction in elderly. To this end, a PVE-correction algorithm was
      applied on the CBF images acquired with spin-echo EPI continuous arterial spin
      labeling MRI (voxel size = 3.4 x 3.4 x 8 mm(3)). Tissue-specific CBF images that
      were independent of voxels' tissue fractional volume were obtained in elderly (N
      = 30) and young (N = 26); mean age difference was 43 years. Globally, PVE
      corrected gray matter CBF was 88.2 +/- 16.1 and 107.3 +/- 17.5 mL/100 g min(-1)
      in elderly and young, respectively. The largest PVE contribution was found in the
      frontal lobe and accounted for an additional 10% and 12% increase in the age
      related CBF difference between men and women, respectively. The GM-to-WM CBF
      ratios were found to be on average 3.5 in elderly and 3.9 in young. Whole brain
      voxelwise comparisons showed marked CBF decrease in anterior cingulate
      (bilateral), caudate (bilateral), cingulate gyrus (bilateral), cuneus (left),
      inferior frontal gyrus (left), insula (left), middle frontal gyrus (left),
      precuneus (bilateral), prefrontal cortex (bilateral), and superior frontal gyrus
      (bilateral) in men and amygdala (bilateral), hypothalamus (left), hippocampus
      (bilateral), and middle frontal gyrus (right) in women.

PMID- 19172646
TI  - Coordinate-based activation likelihood estimation meta-analysis of neuroimaging
      data: a random-effects approach based on empirical estimates of spatial
      uncertainty.
AB  - A widely used technique for coordinate-based meta-analyses of neuroimaging data
      is activation likelihood estimation (ALE). ALE assesses the overlap between foci
      based on modeling them as probability distributions centered at the respective
      coordinates. In this Human Brain Project/Neuroinformatics research, the authors
      present a revised ALE algorithm addressing drawbacks associated with former
      implementations. The first change pertains to the size of the probability
      distributions, which had to be specified by the used. To provide a more
      principled solution, the authors analyzed fMRI data of 21 subjects, each
      normalized into MNI space using nine different approaches. This analysis provided
      quantitative estimates of between-subject and between-template variability for 16
      functionally defined regions, which were then used to explicitly model the
      spatial uncertainty associated with each reported coordinate. Secondly, instead
      of testing for an above-chance clustering between foci, the revised algorithm
      assesses above-chance clustering between experiments. The spatial relationship
      between foci in a given experiment is now assumed to be fixed and ALE results are
      assessed against a null-distribution of random spatial association between
      experiments. Critically, this modification entails a change from fixed- to random
      effects inference in ALE analysis allowing generalization of the results to the
      entire population of studies analyzed. By comparative analysis of real and
      simulated data, the authors showed that the revised ALE-algorithm overcomes
      conceptual problems of former meta-analyses and increases the specificity of the
      ensuing results without loosing the sensitivity of the original approach. It may
      thus provide a methodologically improved tool for coordinate-based meta-analyses
      on functional imaging data.

PMID- 19172647
TI  - Functional brain areas associated with manipulation of a prehensile tool: a PET
      study.
AB  - Using PET, brain areas representing the use of a well-learned tool (chopsticks)
      were investigated in 10 normal common users. The experimental task was to hold
      the tool in their right hand and use it to pick up and transport a small pin from
      a table. Data for the same task performed using only the fingers were also
      obtained as a control. The results showed an extensive overlap in activated areas
      with and without the use of the tool. The tool-use prehension, compared to the
      finger prehension, was associated with higher activities in the caudal-ventral
      premotor, dorsal premotor, superior parietal, posterior intraparietal, middle
      temporal gyrus, and primary sensory, occipital cortices, and the cerebellum.
      These are thus considered to be the human cortical and subcortical substrates
      representing the use of the tool studied. The activity of the posterior
      intraparietal area was negatively correlated with the number of drops of the pin,
      whereas occipital activity was positively correlated with the same error
      parameter. The caudal-ventral premotor and posterior intraparietal areas are
      together known to be involved in tool use-related modulation in peripersonal
      space. The correlation results suggest that this modulation depends on the level
      of performance. The coactivated left middle temporal gyrus further suggests that
      familiarity with a tool as well as the knowledge about its usage plays a role in
      peripersonal space modulation. Superior parietal activation, along with occipital
      activation, indicates the involvement of visual-spatial attention in the tool
      use, possibly reflecting the effect of interaction between the prehension (task)
      and the tool.

PMID- 19172648
TI  - Exploring the relationship between white matter and gray matter damage in early
      primary progressive multiple sclerosis: an in vivo study with TBSS and VBM.
AB  - We investigated the relationship between the damage occurring in the brain normal
      appearing white matter (NAWM) and in the gray matter (GM) in patients with early
      Primary Progressive multiple sclerosis (PPMS), using Tract-Based Spatial
      Statistics (TBSS) and an optimized voxel-based morphometry (VBM) approach. Thirty
      five patients with early PPMS underwent diffusion tensor and conventional imaging
      and were clinically assessed. TBSS and VBM were employed to localize regions of
      lower fractional anisotropy (FA) and lower GM volume in patients compared with
      controls. Areas of anatomical and quantitative correlation between NAWM and GM
      damage were detected. Multiple regression analyses were performed to investigate
      whether NAWM FA or GM volume of regions correlated with clinical scores
      independently from the other and from age and gender. In patients, we found 11
      brain regions that showed an anatomical correspondence between reduced NAWM FA
      and GM atrophy; of these, four showed a quantitative correlation (i.e., the right
      sensory motor region with the adjacent corticospinal tract, the left and right
      thalamus with the corresponding thalamic radiations and the left insula with the
      adjacent WM). Either the NAWM FA or the GM volume in each of these regions
      correlated with disability. These results demonstrate a link between the
      pathological processes occurring in the NAWM and in the GM in PPMS in specific,
      clinically relevant brain areas. Longitudinal studies will determine whether the
      GM atrophy precedes or follows the NAWM damage. The methodology that we described
      may be useful to investigate other neurological disorders affecting both the WM
      and the GM.

PMID- 19172650
TI  - Effects of different viewing perspectives on somatosensory activations during
      observation of touch.
AB  - Previous studies showed that neurons in the monkey premotor cortex became active
      when performing a particular action and also when observing the same action
      performed by others. These findings suggest a mirror system for action
      observation. Recently, bimodal neurons, sensitive both to visual and tactile
      stimulation, were reported in the parietal cortex, suggesting a potential mirror
      neuron system for observing and experiencing tactile stimulation. Subsequently, a
      mirror neuron system for observed touch has been suggested. The current study was
      designed to determine whether the activation of a sensory mirror system during
      touch observation is affected by possible attributions of the observed touch to
      oneself (subjective view) or to somebody else (objective view). In the study,
      healthy volunteers observed video clips of a touched or nontouched hand either in
      an egocentric or in an allocentric perspective during functional magnetic
      resonance imaging. Results showed activation of somatosensory cortices when
      observing the hand being touched in egocentric as well as in the allocentric
      perspectives. Moreover, somatosensory responses differed depending on the
      perspective of the observed touch. We discuss the results in terms of a possible
      mirror neuron system for observed and experienced touch.

PMID- 19172651
TI  - Volume and iron content in basal ganglia and thalamus.
AB  - Magnetic resonance imaging (MRI) studies have highlighted the possibility to
      investigate brain iron content in vivo. In this study, we combined T2*
      relaxometry and automatic segmentation of basal ganglia based on T1-weighted
      images in healthy subjects, with the aim of characterizing age related changes in
      volume and iron-related relaxivity values (R2*) of these structures. Thirty
      healthy subjects underwent MR imaging at 3 Tesla. Mean R2* values and volumes
      were calculated for the selected subcortical structures (pallidum, putamen,
      thalamus and caudate nucleus). Our results showed a correlation between R2*
      values and iron concentration as calculated from published post-mortem data.
      Furthermore, we observed a shrinkage/iron increase with a different pattern in
      the anatomical regions selected in this work, suggesting that the age-related
      changes on these MR parameters are specific to the subcortical structure
      considered. In particular, the putamen demonstrated a decrease of volume and an
      increase of iron level, with the posterior region of this structure appearing
      more disposed to iron deposition. Our work suggests that combining volumetry and
      iron estimation in MRI permits to investigate in vivo neurophysiological and
      neuropathological changes of basal ganglia.

PMID- 19172652
TI  - Activated region fitting: a robust high-power method for fMRI analysis using
      parameterized regions of activation.
AB  - An important issue in the analysis of fMRI is how to account for the spatial
      smoothness of activated regions. In this article a method is proposed to
      accomplish this by modeling activated regions with Gaussian shapes. Hypothesis
      tests on the location, spatial extent, and amplitude of these regions are
      performed instead of hypothesis tests of individual voxels. This increases power
      and eases interpretation. Simulation studies show robust hypothesis tests under
      misspecification of the shape model, and increased power over standard techniques
      especially at low signal-to-noise ratios. An application to real single-subject
      data also indicates that the method has increased power over standard methods.

PMID- 19172649
TI  - Automated 3D mapping of hippocampal atrophy and its clinical correlates in 400
      subjects with Alzheimer's disease, mild cognitive impairment, and elderly
      controls.
AB  - We used a new method we developed for automated hippocampal segmentation, called
      the auto context model, to analyze brain MRI scans of 400 subjects from the
      Alzheimer's disease neuroimaging initiative. After training the classifier on 21
      hand-labeled expert segmentations, we created binary maps of the hippocampus for
      three age- and sex-matched groups: 100 subjects with Alzheimer's disease (AD),
      200 with mild cognitive impairment (MCI) and 100 elderly controls (mean age:
      75.84; SD: 6.64). Hippocampal traces were converted to parametric surface meshes
      and a radial atrophy mapping technique was used to compute average surface models
      and local statistics of atrophy. Surface-based statistical maps visualized links
      between regional atrophy and diagnosis (MCI versus controls: P = 0.008; MCI
      versus AD: P = 0.001), mini-mental state exam (MMSE) scores, and global and sum
      of-boxes clinical dementia rating scores (CDR; all P < 0.0001, corrected). Right
      but not left hippocampal atrophy was associated with geriatric depression scores
      (P = 0.004, corrected); hippocampal atrophy was not associated with subsequent
      decline in MMSE and CDR scores, educational level, ApoE genotype, systolic or
      diastolic blood pressure measures, or homocysteine. We gradually reduced sample
      sizes and used false discovery rate curves to examine the method's power to
      detect associations with diagnosis and cognition in smaller samples. Forty
      subjects were sufficient to discriminate AD from normal and correlate atrophy
      with CDR scores; 104, 200, and 304 subjects, respectively, were required to
      correlate MMSE with atrophy, to distinguish MCI from normal, and MCI from AD.

PMID- 19172653
TI  - Diminished neural sensitivity to irregular facial expression in first-episode
      schizophrenia.
AB  - INTRODUCTION: Blunted, inappropriate affective-social behavior is a hallmark of
      early schizophrenia, possibly corresponding to reduced ability to recognize and
      express emotions. It is yet unknown if this affective deficiency relates to
      disturbed neural sensitivity to facial expressions or to overall face processing.
      In a previous imaging study, healthy subjects showed less suppression of the
      fusiform gyrus (FG) to repeated presentation of the same transfigured-bizarre
      face relative to regular face. We assumed that the FG in schizophrenia will show
      reduced repetition related sensitivity to transfigured-bizarre faces, while
      having overall normal response to faces. METHODS: Ten first-episode patients with
      schizophrenia and 10 controls rated the bizarreness of upright and inverted
      faces. In an fMRI study, another group of 17 first-episode patients with
      schizophrenia and 12 controls viewed regular and transfigured-bizarre faces in
      blocks. Each block contained regular- or transfigured-bizarre faces of either
      different or same individual, presented in an upright or inverted orientation.
      RESULTS: Patients in comparison with controls rated irregular faces as less
      bizarre. The FG, in patients and controls exhibited similar response to inverted
      faces, suggesting normal face processing. In contrast, the FG only in patients,
      showed similar suppression to repeated transfigured-bizarre and regular faces.
      Finally, the FG in patients compared with controls showed reduced functional
      connectivity with the amygdala and prefrontal cortex. CONCLUSION: Patients with
      schizophrenia already at first-episode, showed reduced behavioral and neural
      sensitivity to bizarre facial expressions. Possibly, this deficiency is related
      to disturbed modulations of emotion-related face processing in the FG by the
      amygdala and prefrontal cortex.

PMID- 19172654
TI  - Differential force scaling of fine-graded power grip force in the sensorimotor
      network.
AB  - Force scaling in the sensorimotor network during generation and control of static
      or dynamic grip force has been the subject of many investigations in monkeys and
      human subjects. In human, the relationship between BOLD signal in cortical and
      subcortical regions and force still remains controversial. With respect to grip
      force, the modulation of the BOLD signal has been mostly studied for forces often
      reaching high levels while little attention has been given to the low range for
      which electrophysiological neuronal correlates have been demonstrated. We thus
      conducted a whole-brain fMRI study on the control of fine-graded force in the low
      range, using a power grip and three force conditions in a block design.
      Participants generated on a dynamometer visually guided repetitive force pulses
      (ca. 0.5 Hz), reaching target forces of 10%, 20%, and 30% of maximum voluntary
      contraction. Regions of interest analysis disclosed activation in the entire
      cortical and subcortical sensorimotor network and significant force-related
      modulation in several regions, including primary motor (M1) and somatosensory
      cortex, ventral premotor and inferior parietal areas, and cerebellum. The BOLD
      signal, however, increased monotonically with force only in contralateral M1 and
      ipsilateral anterior cerebellum. The remaining regions were activated with force
      in various nonlinear manners, suggesting that other factors such as visual input,
      attention, and muscle recruitment also modulate the BOLD signal in this
      visuomotor task. These findings demonstrate that various regions of the
      sensorimotor network participate differentially in the production and control of
      fine-graded grip forces.

PMID- 19172655
TI  - Changes in the interaction of resting-state neural networks from adolescence to
      adulthood.
AB  - This study examined how the mutual interactions of functionally integrated neural
      networks during resting-state fMRI differed between adolescence and adulthood.
      Independent component analysis (ICA) was used to identify functionally connected
      neural networks in 100 healthy participants aged 12-30 years. Hemodynamic
      timecourses that represented integrated neural network activity were analyzed
      with tools that quantified system "causal density" estimates, which indexed the
      proportion of significant Granger causality relationships among system nodes.
      Mutual influences among networks decreased with age, likely reflecting stronger
      within-network connectivity and more efficient between-network influences with
      greater development. Supplemental tests showed that this normative age-related
      reduction in causal density was accompanied by fewer significant connections to
      and from each network, regional increases in the strength of functional
      integration within networks, and age-related reductions in the strength of
      numerous specific system interactions. The latter included paths between lateral
      prefrontal-parietal circuits and "default mode" networks. These results
      contribute to an emerging understanding that activity in widely distributed
      networks thought to underlie complex cognition influences activity in other
      networks.

PMID- 19172656
TI  - Re: Life-threatening posttonsillectomy hemorrhage.

PMID- 19172658
TI  - Elevated glutamate and NMDA disrupt production of the second messenger cyclic GMP
      in the early postnatal mouse cortex.
AB  - The second messenger cyclic guanosine monophosphate (cGMP) plays many roles
      during nervous system development. Consequently, cGMP production shows complex
      patterns of regulation throughout early development. Elevated glutamate levels
      are known to increase cGMP levels in the mature nervous system. A number of
      clinical conditions including ischemia and perinatal asphyxia can result in
      elevated glutamate levels in the developing brain. To investigate the effects of
      elevated glutamate levels on cGMP in the developing cortex we exposed mouse brain
      slices to glutamate or N-methyl D-aspartate (NMDA). We find that at early
      postnatal stages when the endogenous production of cGMP is high, glutamate or
      NMDA exposure results in a significant lowering of the overall production of cGMP
      in the cortex, unlike the situation in the mature brain. However, this response
      pattern is complex with regional and cell-type specific exceptions to the overall
      lowered cGMP production. These data emphasize that the response of the developing
      brain to physiological disturbances can be different from that of the mature
      brain, and must be considered in the context of the developmental events
      occurring at the time of disturbance.

PMID- 19172659
TI  - Desensitization to media violence over a short period of time.
AB  - This study investigated the desensitization to violence over a short period of
      time. Participants watched nine violent movie scenes and nine comedy scenes, and
      reported whether they enjoyed the violent or comedy scenes and whether they felt
      sympathetic toward the victim of violence. Using latent growth modeling, analyses
      were carried out to investigate how participants responded to the different
      scenes across time. The findings of this study suggested that repeated exposure
      to media violence reduces the psychological impact of media violence in the short
      term, therefore desensitizing viewers to media violence. As a result, viewers
      tended to feel less sympathetic toward the victims of violence and actually enjoy
      more the violence portrayed in the media. Additionally, desensitization to media
      violence was better represented by a curvilinear pattern, whereas desensitization
      to comedy scenes was better represented by a linear pattern. Finally, trait
      aggression was not related to the pattern of change over time, although
      significant effects were found for initial reports of enjoyment and sympathy.

PMID- 19172660
TI  - Development of adolescence-limited, late-onset, and persistent offenders from age
      8 to age 48.
AB  - This article investigates the life success at ages 32 and 48 of four categories
      of males: nonoffenders, adolescence-limited offenders (convicted only at ages 10
      20), late-onset offenders (convicted only at ages 21-50), and persistent
      offenders (convicted at both ages 10-20 and 21-50). In the Cambridge Study in
      Delinquent Development, 411 South London males have been followed up from age 8
      to 48 in repeated personal interviews. There was considerable continuity in
      offending over time. Persistent offenders had the longest criminal careers
      (averaging 18.4 years), and most of them had convictions for violence. Persistent
      offenders were leading the most unsuccessful lives at ages 32 and 48, although
      all categories of males became more successful with age. By age 48, the life
      success of adolescence-limited offenders was similar to that of nonoffenders. The
      most important risk factors at ages 8-18 that predicted which offenders would
      persist after age 21 were heavy drinking at age 18, hyperactivity at ages 12-14,
      and low popularity and harsh discipline at ages 8-10. The most important risk
      factors that predicted which nonoffenders would onset after age 21 were poor
      housing and low nonverbal IQ at ages 8-10, high neuroticism at age 16, and anti
      establishment attitudes and motoring convictions at age 18. It was suggested that
      nervousness and neuroticism may have protected children at risk from offending in
      adolescence and the teenage years.

PMID- 19172661
TI  - Normal renal arterial anatomy assessed by multidetector CT angiography: are there
      differences between men and women?
AB  - The purpose of this study was to determine renal arterial anatomy and gender
      differences in adults without renovascular disease using multidetector computed
      tomography angiography (MDCTA). MDCTA datasets of 399 patients were
      retrospectively reviewed. Measurements of the aortorenal diameters, the
      angulation of the renal ostia and pedicles as well as the distance between the
      origins of the renal arteries were measured. Differences in measurements between
      genders were tested for statistical significance using analysis of variance
      (ANOVA) and Pearson's Chi-Square tests. A total of 798 renal arteries were
      available for analysis in 207 female (mean age = 52.91 years) and 192 male
      patients (mean age = 53.04 years). Female patients were found to have smaller
      aortae (at the level of the right renal ostium) and bilateral renal arteries than
      males (mean aortic diameter M/F = 18.33/15.89 mm, mean right renal artery ostial
      diameter M/F = 5.06/4.59 mm, mean left ostial renal diameter M/F = 5.14/4.66 mm)
      (p < .001). There was no statistical significance for the renal ostia level in
      relation to the vertebrae and the majority of renal arteries originated at the L1
      and L2 levels. The longitudinal distance between right and left renal artery
      ostia ranged from 0 to 32 mm (mean = 4,6 mm, median = 5mm). The mean
      anteroposterior orientation of the right renal ostia was M/F = 29.45
      degrees/28.20 degrees , and M/F = -7.96 degrees/-11.14 degrees for left renal
      artery ostia. The mean anteroposterior orientation of the right renal pedicle was
      M/F = 41.37 degrees/44.34 degrees and M/F = 42.31 degrees/43.95 degrees for the
      left pedicle. There are some differences in normal renal arterial anatomy between
      genders. Normal renal arterial information is useful not only for planning and
      performing of endovascular and laparoscopic urologic procedures, but also for
      medical device development.

PMID- 19172662
TI  - Cerebral biometry in fetal magnetic resonance imaging: new reference data.
AB  - OBJECTIVES: To provide normal magnetic resonance imaging (MRI) reference
      biometric data of the fetal brain, to evaluate reproducibility and gender effect,
      to compare the two cerebral hemispheres and to compare MRI with ultrasonographic
      biometry, in a large cohort. METHODS: Normal cerebral fetal MRI examinations were
      collected prospectively and several parameters were measured: the supratentorial
      space (bone and cerebral fronto-occipital and biparietal (BPD) diameters), the
      length of the corpus callosum (LCC), the surface area, height and anteroposterior
      diameter of the vermis, the transverse cerebellar diameter (TCD) and the
      anteroposterior diameter of the pons. We evaluated the interobserver
      reproducibility of measurements and the possible gender effect on measurements of
      bone BPD, TCD and LCC. We compared right and left hemispheres, right and left
      atria and ultrasound and MRI measurements. RESULTS: The study included 589
      fetuses, ranging from 26 to 40 weeks. Normal values (from 3(rd) to 97(th)
      percentile) are provided for each parameter. Interobserver agreement was
      excellent, with an intraclass correlation coefficient (ICC) > 0.75 for many
      parameters. The gender effect was evaluated in 372 cases and did not reveal any
      clinically meaningful difference. Comparison between the right and left cerebral
      hemispheres and between the right and left atria did not reveal any meaningful
      differences. Ultrasound and MRI measurements of BPD and TCD were compared in 94
      cases and 48 cases, respectively, and the agreement was excellent (ICC = 0.85).
      CONCLUSIONS: We present new reproducible reference charts for cerebral MRI
      biometry at 26-40 weeks' gestation, from a large cohort of fetuses.

PMID- 19172663
TI  - Effects of grape seed extract and its ethylacetate/ethanol fraction on blood
      glucose levels in a model of type 2 diabetes.
AB  - The present study observed the effects of grape seed extract (GSE) and its
      ethylacetate (E) and ethylacetate/ethanol (EE) fractions on blood glucose levels
      in C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice at 4-12 weeks of age. In the GSE- and
      EE fraction-treated db/db group, the blood glucose concentration began to be
      lower than that in the vehicle-treated db/db group at 6 weeks after treatment,
      while the blood glucose concentration in the E fraction-treated db/db group was
      similar to that in the vehicle-treated db/db group. The glycosylated hemoglobin
      (HbA1c) level in the vehicle-treated db/db groups was 9.3%, whereas HbA1c levels
      in the GSE- and EE fraction-treated db/db group decreased significantly to 5.7%
      and 6.1%, respectively, at 8 weeks after treatment. However, administration of
      GSE and its EE fraction did not show any significant effects on body weights and
      food consumption in db/db mice. These results suggest that GSE and its EE
      fraction have a potential to decrease the blood glucose and HbA1c level, which is
      applicable to good healthy foods for reducing blood glucose levels.

PMID- 19172664
TI  - Inhibition of P-glycoprotein function by procyanidine on blood-brain barrier.
AB  - The inhibitory effects of procyanidine, one of the components from the bark of
      Pinus massoniana Lamb, on the P-glycoprotein (P-gp) function of the blood-brain
      barrier (BBB) were studied using in vitro rat brain microvessel endothelial cells
      (RBMECs) and nude mice transplanted with human cerebroma. Quantitative
      accumulation and efflux of rhodamine 123 (Rh123), a P-gp substrate, were
      determined using a fluorescence spectrophotometer as a measure of P-gp function.
      Procyanidine markedly increased the accumulation of Rh123 by inhibiting its
      efflux in a dose-dependent manner. A 5-fold increase in cellular Rh123 was
      observed for procyanidine at 10 micromol/L. The verapamil-stimulated ATPase
      activity in plasma membrane vesicles from the RBMECs was estimated by measuring
      inorganic phosphate liberation. Procyanidine significantly inhibited the
      verapamil-induced P-gp ATPase activity by 78% when pretreated with 10 micromol/L
      in a concentration-dependent manner. The inhibition of P-gp by procyanidine was
      suggested to be at least partly due to its inhibition of P-gp ATPase.
      Procyanidine markedly improved the therapeutic effects of adriamycin (ADM) on
      nude mice transplanted with human cerebroma, compared with solitary treatment of
      ADM. The combination of 80 mg/kg procyanidine with 2 mg/kg ADM significantly
      elevated the days of survival with an increase in life span of 76%. The findings
      suggested that procyanidine was a potent inhibitor of P-gp on BBB and could
      improve the therapeutic effects on cerebral tumors of some drugs which are
      difficult to accumulate in the brain.

PMID- 19172665
TI  - Identification of plant extracts with potential antidiabetic properties: effect
      on human peroxisome proliferator-activated receptor (PPAR), adipocyte
      differentiation and insulin-stimulated glucose uptake.
AB  - Thiazolidinediones (TZDs) are insulin sensitizing drugs used to treat type 2
      diabetes. The primary target of the TZDs is the peroxisome proliferator-activated
      receptor (PPAR) gamma, a key regulator of adipogenesis and glucose homeostasis.
      Currently prescribed TZDs are full PPARgamma agonists, and their use is
      associated with several side effects. Partial PPARgamma agonists appear to be
      associated with fewer side effects but may still confer the desired insulin
      sensitizing action. Extracts from common medicinal/food plants were tested in a
      screening platform comprising a series of bioassays, including tests for
      PPARgamma, alpha and delta transactivation, adipocyte differentiation and insulin
      stimulated glucose uptake, allowing identification of plants containing
      potentially interesting PPAR agonists. Twenty-two plant extracts out of 133 were
      found to increase insulin-stimulated glucose uptake and 18 extracts were found to
      activate PPARgamma, 3 to activate PPARalpha and gamma, 6 to activate PPARdelta
      and gamma, and 9 to activate PPARgamma, alpha and delta. Among the 24 different
      plant species tested in the platform, 50% were shown to contain compounds capable
      of activating PPARgamma and stimulating insulin-dependent glucose uptake with no
      or little effect on adipocyte differentiation warranting further studies and
      characterization.

PMID- 19172667
TI  - Garcinia mangostana L.: a phytochemical and pharmacological review.
AB  - Garcinia mangostana L. (mangosteen, Clusiaceae) has a long history of use as a
      medical plant, mostly in Southeast Asia. This is a review of the phytochemistry
      and pharmacology of mangosteen. Traditionally mangosteen is famous for its
      antiinflammatory properties and is used in the treatment of skin infections and
      wounds. Other applications include the therapy of various conditions such as
      dysentery, different urinary disorders, cystitis and gonorrhoea. This review
      highlights the development of this botanical drug into a widely used
      nutraceutical. Products derived from G. mangostana are now distributed
      increasingly all over the world. This has given rise to a concomitant increase in
      research on the phytochemical constituents and biological activity of mangosteen.
      Central to the biological activity of the species are xanthones which are
      reviewed in detail. A comprehensive assessment of the biological activities of
      individual xanthones as well as extracts of G. mangostana is included. In
      addition, its potential in terms of developing novel drug leads is assessed.
      Products containing its fruits are now sold widely as 'liquid botanical
      supplements', but evidence for the health benefits of these products is still
      lacking. As shown here, a serious weakness in our knowledge is the lack of
      clinical data and it is not yet clear to what extent the findings about
      pharmacological activities are of potential clinical relevance.

PMID- 19172666
TI  - Chemical and antioxidant evaluation of Indian gooseberry (Emblica officinalis
      Gaertn., syn. Phyllanthus emblica L.) supplements.
AB  - Indian gooseberry (Emblica officinalis Gaertn.) (Euphorbiaceae) has a
      distinguished history in Ayurveda medicine and is ascribed a number of medicinal
      properties and as a dietary supplement, its use is increasing in Western
      countries. It is thought that its beneficial properties are a function of its
      antioxidant potency. The study investigated the chemistry and antioxidant
      properties of four commercial E. officinalis fruit extracts in order to determine
      if there are any qualitative-quantitative differences. All extracts produced
      positive responses in the total phenol, total flavonoid and total tannin assays.
      The presence of predominantly (poly)phenolic analytes, e.g. ellagic and gallic
      acids and corilagin, was confirmed by RP-HPLC coupled with photodiode array
      detection. Despite ascorbic acid being a major constituent of E. officinalis
      fruits, the furanolactone could not be identified in one of the samples. The
      extracts demonstrated varying degrees of antioxidative efficacy. The extract
      designated IG-3 was consistently amongst the most effective extracts in the
      iron(III) reduction and 1,1-diphenyl-2-picrylhydrazyl and superoxide anion
      radical scavenging assays while the extract designated IG-1 demonstrated the best
      hydroxyl radical scavenging activity. All extracts appeared to be incapable of
      chelating iron(II) at realistic concentrations.

PMID- 19172668
TI  - Antipsychotic choice in early-onset schizophrenia.

PMID- 19172669
TI  - Special issue on human computing.

PMID- 19172670
TI  - Letter to editor in response to "Prevention of pediatric graft coronary artery
      disease: atorvastatin", by Chin et al.

PMID- 19172671
TI  - One-third of adult smokers have a mental illness.

PMID- 19172672
TI  - Follow-up of intensive glucose control in type 2 diabetes.

PMID- 19172673
TI  - Follow-up of intensive glucose control in type 2 diabetes.

PMID- 19172674
TI  - Follow-up of intensive glucose control in type 2 diabetes.

PMID- 19172675
TI  - Breast reconstruction after breast-cancer surgery.

PMID- 19172676
TI  - Breast reconstruction after breast-cancer surgery.

PMID- 19172677
TI  - Breast reconstruction after breast-cancer surgery.

PMID- 19172678
TI  - Executive physicals.

PMID- 19172679
TI  - Executive physicals.

PMID- 19172680
TI  - From signal to dialogue: Dynamic aspects of hearing, language and cognition.
      Proceedings of an international conference, September 7-8, 2007, Linkoping
      University, Sweden.

PMID- 19172681
TI  - Prevalence of social phobia in non-demented elderly from a swedish population
      study.
AB  - OBJECTIVE: To examine the prevalence of social phobia, and how the different
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
      diagnostic components of social phobia influence prevalence rates, among a
      population sample aged 70 years and older. DESIGN: A general population sample
      was investigated in 2000-2001 with semistructured psychiatric examinations,
      including the Comprehensive Psychopathological Rating Scale, the Mini
      International Neuropsychiatric Interview, the Global Assessment of Functioning
      (GAF) scale, and the Mini Mental State Examination. SETTING: General population
      Participants: Randomized sample of 914 nondemented elderly, response rate 68%.
      The sample was stratified into two age groups: 70-year olds (N = 338 women and
      224 men) and aged 78 and above (N = 352 women). MEASUREMENTS: Social phobia
      according to DSM-IV requiring: a) fearing social situations, b) experiencing the
      fear as unreasonable or excessive, c) avoiding feared social situations or
      enduring them with intense anxiety or distress, and d) that this causes social
      consequences. RESULTS: The 1-month prevalence of social phobia was 1.9% (N = 17),
      an additional 1.6% (N = 15) fulfilled criteria a, c, and d, but not b. Thus, 3.5%
      had "social phobia" that caused social consequences. This was related to lower
      GAF-score and concurrent depression,panic attacks, and agoraphobia. Almost one
      fourth (N = 220) of the total sample feared social situations. This was more
      common in 70-year-old women compared with 70-year-old men (29.9% versus 20.5%),
      and to women aged 78-92 years (21.0%). CONCLUSIONS: Our results indicate that DSM
      IV criteria exclude a large group of individuals with social phobia. It could be
      discussed whether DSM-IV criteria should be revised to also encompass these
      individuals.

PMID- 19172682
TI  - Physical disability and depressive symptomatology in an elderly population: a
      complex relationship. The Italian Longitudinal Study on Aging (ILSA).
AB  - OBJECTIVES: Depressive symptoms (DS) are very frequent in elderly individuals and
      are associated with negative outcomes. This study was undertaken to evaluate
      whether DS predict physical disability in this population. METHODS: A
      prospective,community-based cohort study, this work included 5,632 individuals
      aged 65-84 years, who were recruited from the demographic registries of eight
      Italian municipalities in 1992. The complete data of 3,256 subjects were
      collected and analyzed. DS were assessed using the Geriatric Depression Scale
      with a score > or = 10/30 indicating DS. All traditional risk factors for
      disability established by questionnaires and physical examinations were assessed
      at baseline. The outcomes were self-reported disability on the activities of
      daily living (ADL) test and the performance-based physical function assessment
      (Physical Performance Tests, PPT). The contribution of the predictive variables
      to the outcomes evaluated after a mean follow-up of 3.5 +/- 0.4 years was
      assessed using hierarchical logistic nested models. RESULTS: Baseline DS was
      associated with higher rates of ADL disability (odds ratio [OR] 1.73,
      95%confidence interval [CI] 1.12-2.66) and PPT disability (OR 1.83, 95% CI 1.17
      2.85)in men and with ADL disability (OR 1.81, 95% CI 1.28 -2.55) in women. The
      independent predictors of PPT disability in women were arthritis (OR 2.13, 95% CI
      1.28 -3.53) and age (OR 1.09; 95% CI 1.03-1.15). CONCLUSIONS: This study provides
      evidence that older persons who report DS are at higher risk of subsequent
      physical decline. In women, arthritis is a more powerful predictor of preclinical
      disability, as measured by PPT.

PMID- 19172683
TI  - 60 years studying heart-disease risk.

PMID- 19172684
TI  - Mixed results for disease-modification strategies for Alzheimer's disease.

PMID- 19172685
TI  - Industry concern over EU hepatotoxicity guidance.

PMID- 19172686
TI  - An audience with...Frank Torti.

PMID- 19172687
TI  - Osteoporosis: overview and pipeline.

PMID- 19172688
TI  - Alvimopan.

PMID- 19172689
TI  - Perspectives on NMR in drug discovery: a technique comes of age.
AB  - In the past decade, the potential of harnessing the ability of nuclear magnetic
      resonance (NMR) spectroscopy to monitor intermolecular interactions as a tool for
      drug discovery has been increasingly appreciated in academia and industry. In
      this Perspective, we highlight some of the major applications of NMR in drug
      discovery, focusing on hit and lead generation, and provide a critical analysis
      of its current and potential utility.

PMID- 19172690
TI  - T-cell activation by dendritic cells in the lymph node: lessons from the movies.
AB  - Interactions between T cells and dendritic cells (DCs) in the lymph nodes are
      crucial for initiating cell-mediated adaptive immune responses. With the help of
      two-photon imaging, the complexity of these cellular contacts in vivo has
      recently been captured in time-lapse movies in several immunological contexts.
      Well beyond the satisfaction of seeing a T-cell response as it happens, these
      experiments provide fundamental insights into the regulation and the biological
      meaning of T-cell-DC contact dynamics. This Review focuses on how this emerging
      field is changing our perception of T-cell activation by DCs.

PMID- 19172691
TI  - Vitamin effects on the immune system: vitamins A and D take centre stage.
AB  - Vitamins are essential constituents of our diet that have long been known to
      influence the immune system. Vitamins A and D have received particular attention
      in recent years as these vitamins have been shown to have an unexpected and
      crucial effect on the immune response. We present and discuss our current
      understanding of the essential roles of vitamins in modulating a broad range of
      immune processes, such as lymphocyte activation and proliferation, T-helper-cell
      differentiation, tissue-specific lymphocyte homing, the production of specific
      antibody isotypes and regulation of the immune response. Finally, we discuss the
      clinical potential of vitamin A and D metabolites for modulating tissue-specific
      immune responses and for preventing and/or treating inflammation and
      autoimmunity.

PMID- 19172693
TI  - Mesenchymal stem cells in health and disease.
AB  - Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal stem cells
      that can be isolated from many adult tissues. They can differentiate into cells
      of the mesodermal lineage, such as adipocytes, osteocytes and chondrocytes, as
      well as cells of other embryonic lineages. MSCs can interact with cells of both
      the innate and adaptive immune systems, leading to the modulation of several
      effector functions. After in vivo administration, MSCs induce peripheral
      tolerance and migrate to injured tissues, where they can inhibit the release of
      pro-inflammatory cytokines and promote the survival of damaged cells. This Review
      discusses the targets and mechanisms of MSC-mediated immunomodulation and the
      possible translation of MSCs to new therapeutic approaches.

PMID- 19172692
TI  - Formation and function of the lytic NK-cell immunological synapse.
AB  - The natural killer (NK)-cell immunological synapse is the dynamic interface
      formed between an NK cell and its target cell. Formation of the NK-cell
      immunological synapse involves several distinct stages, from the initiation of
      contact with a target cell to the directed delivery of lytic-granule contents for
      target-cell lysis. Progression through the individual stages is regulated, and
      this tight regulation underlies the precision with which NK cells select and kill
      susceptible target cells (including virally infected cells and cancerous cells)
      that they encounter during their routine surveillance of the body.

PMID- 19172694
TI  - The art of measuring gastrin in plasma: a dwindling diagnostic discipline?
AB  - The gastrointestinal hormone gastrin is measured in plasma in physiological,
      pathophysiological and diagnostic investigations. In the diagnosis of
      hypergastrinaemic diseases such as gastrinomas and gastric achlorhydria,
      measurement of gastrin concentrations in circulation is crucial. Gastrin
      circulates, however, not as a single peptide but as a mixture of peptides of
      different lengths and amino acid derivatizations. Moreover, in hypergastrinaemia
      the peptide pattern changes. Consequently, diagnostic gastrin measurements
      require immunoassays that recognize the pathological plasma patterns, which are
      characterized by a predominance of the large peptides (gastrin-34 and gastrin-71)
      and less, if any, of the shorter main form of gastrin in normal tissue, gastrin
      17. Alternatively, and in specific cases, "processing-independent assays" (PIA)
      for progastrin may be considered, since hypersecreting gastrin cells also release
      substantial amounts of biosynthetic precursors and processing intermediates.
      Recently, gastrin kits that do not take the pathological plasma patterns into
      account have been marketed and may miss the diagnosis. Therefore, proper
      diagnosis of gastrinomas and other hypergastrinaemic diseases requires insight
      into cellular gastrin synthesis and peripheral metabolism, and also into the
      design of useful immunoassays. This review discusses the art of measuring gastrin
      in plasma with adequate diagnostic specificity.

PMID- 19172695
TI  - Circulating serum trefoil factors increase dramatically during pregnancy.
AB  - OBJECTIVE: Trefoil factors (TFF1-3) are 7-12 kDa peptides secreted by mucosal
      surfaces, with changing levels of expression reflected in serum concentrations.
      The genes for the peptides are located on chromosome 21, the chromosome
      duplicated in trisomy 21. We studied the levels of circulating TFFs in pregnant
      women carrying trisomy 21 foetuses and in women with normal pregnancies,
      throughout pregnancy and postpartum. MATERIAL AND METHODS: Employing ELISA
      methods, serum collected at gestational weeks (GW) 18, 32, 39 and 8 weeks
      postpartum from women carrying normal foetuses (n=141) was analysed for TFFs. In
      addition, serum collected at GW 6-14 (median = 10) from women carrying trisomy 21
      foetuses (n=48) or healthy foetuses (n=46) was analysed. RESULTS: Peaking at 39
      GW, concentrations of TFF2 and TFF3 were 3.5 and 47 times higher, respectively,
      than postpartum. Postpartum levels were comparable to concentrations previously
      measured in nonpregnant women. TFF1 concentrations rose throughout pregnancy and
      postpartum, being 1.5 times higher postpartum compared to 18 GW. No differences
      in the levels of TFFs were observed between women carrying trisomy 21 and those
      with healthy foetuses. To our knowledge, circulating TFF3 has never been reported
      to reach the levels observed here. Also, the pattern of increase is unusual, as
      previous reports have shown parallel increases in TFF1 and TFF3 with no
      alterations in TFF2. CONCLUSIONS: Our results demonstrate that circulating TFFs
      are not candidate markers of trisomy 21 in first-trimester pregnancies, but raise
      intriguing questions concerning the origin of TFFs produced during pregnancy and
      their physiological function.

PMID- 19172696
TI  - The reduced folate carrier (RFC1) 80G > A and folate hydrolase 1 (FOLH1) 1561C >
      T polymorphisms and the risk of colorectal cancer: a nested case-referent study.
AB  - OBJECTIVE: Polymorphisms in genes involved in folate uptake and metabolism may
      affect folate status and, thereby, the risk of cancer. In this nested case
      referent study, we related two such polymorphisms, reduced folate carrier (RFC1)
      80G > A and folate hydrolase 1 (FOLH1) 1561C > T, to the risk of colorectal
      cancer, taking into account pre-diagnostic plasma folate and total homocysteine
      concentrations and the MTHFR 677C > T polymorphism, which were analysed in a
      previous study. MATERIAL AND METHODS: Subjects were 220 cases and 414 matched
      referents from the population-based Northern Sweden Health and Disease Study.
      RESULTS: The RFC1 80A-allele was associated with reduced plasma folate and
      elevated plasma total homocysteine concentrations, but the result was
      statistically significant only for folate. In contrast, the FOLH1 1561T-allele
      was associated with higher plasma folate and reduced plasma total homocysteine
      concentrations, and the result was statistically significant only for
      homocysteine. Neither polymorphism was related to the risk of colorectal cancer,
      either in univariate analysis or after adjusting for body mass index, current
      smoking, recreational and occupational physical activity and alcohol intake.
      Further adjustment for folate or homocysteine status or the MTHFR 677C > T
      polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype
      in combination with low plasma folate concentrations or the MTHFR 677TT genotype
      had a reduced risk of colorectal cancer of borderline statistical significance.
      CONCLUSIONS: These findings suggest that although the RFC1 80G > A and FOLH1
      1561C > T polymorphisms may influence folate status, they are not likely to have
      a major independent role in the development of colorectal cancer.

PMID- 19172697
TI  - Accuracy of N-terminal-pro-atrial natriuretic peptide in patients admitted to
      emergency department.
AB  - OBJECTIVE: B-type natriuretic peptide (BNP) and N-terminal-pro-BNP (Nt-proBNP)
      are commonly used for the triage of patients in the emergency department (ED)
      with dyspnoea and/or chest pain. The aim of our study was to determine the
      accuracy of N-terminal-pro-ANP (Nt-proANP) in such patients. MATERIAL AND
      METHODS: Nt-proANP was measured by home-made radioimmunoassay in 137 ED patients
      admitted with cardiovascular and/or pulmonary disorders. BNP and Nt-pro-BNP were
      determined with automated assays. Final diagnosis was confirmed at discharge or
      after follow-up. RESULTS: Nt-proANP levels were significantly influenced by the
      diagnostic subgroups (ANOVA: p<0.001) and were [geometric mean (range)]: 19727
      ng/L (5260-45200) in congestive heart failure (CHF, n=31), 6575 ng/L (1350-36000)
      in coronary artery disease (CAD, n=19), 5324 ng/L (1710-13150) in pulmonary
      embolism (PE, n=20), 5035 ng/L (1510-16600) in pulmonary diseases (PD, n=24) and
      3001 ng/L (750-11860) in patients without cardiopulmonary diseases (n=43).
      Pairwise comparisons demonstrated that CHF patients had Nt-pro-ANP values higher
      than all other groups (p<0.05) and that patients without cardiopulmonary diseases
      had the lowest values (p<0.05). For diagnosis of CHF, the area under the ROC
      curve of Nt-proANP was 0.94 (95 % CI: 0.89-0.98) and was equivalent to Nt-proBNP
      (0.91; p=0.284) and BNP (0.93; p=0.572). CONCLUSIONS: The diagnostic accuracy of
      Nt-proANP was equivalent to BNP and Nt-proBNP in the present cohort of patients
      admitted to ED with dyspnoea and/or chest pain.

PMID- 19172698
TI  - Nt-proBNP in haemodialysis patients: a preliminary study.
AB  - OBJECTIVE: N-terminal pro-brain natriuretic peptide (Nt-proBNP) is a marker of
      left ventricular function. Although many factors can increase left ventricular
      dysfunction in haemodialysis patients, the role of Nt-proBNP is uncertain.
      MATERIAL AND METHODS: Serum concentrations of Nt-proBNP and troponin T were
      measured by electrochemiluminescence and C-reactive protein by immunoturbidimetry
      in 52 dialysis patients followed-up for 36 months. RESULTS: Nt-proBNP correlated
      (p<0.05) with time on haemodialysis (rho=0.345), left ventricular mass index
      (r=0.596), troponin T level (r=0.605) and age (r=0.296). Patients with a history
      of heart disease showed higher levels of Nt-proBNP (median; minimum-maximum
      ngl/L) (15,571; 1,553-209,451) than those without (4,535; 751-115,078) (p<0.01).
      Sensitivity and specificity of Nt-proBNP in the detection of left ventricular
      dysfunction (ventricular ejection fraction < 45%) were 1.0 and 0.782,
      respectively. In the univariate analysis, patients with Nt-proBNP levels > or =
      33,314 ng/L, CRP > or = 5 mg/L or troponin T > or = 0.1 microg/L had poorer
      probabilities of 1-year, 2-year and 3-year survival than patients with lower
      levels. Unfavourable prognostic factors in the multivariate analysis were CRP > 5
      mg/L and Tn T > 0.1 microg/L. CONCLUSIONS: Nt-proBNP showed good diagnostic
      performance for detecting left ventricular dysfunction and was an important
      predictor of mortality in haemodialysis patients in the univariate analysis. In
      the multivariate analysis, Nt-proBNP lost its prognostic value, whereas for CRP
      and Tn T it was maintained.

PMID- 19172699
TI  - Haemoglobin, C-reactive protein and androgen levels in uncomplicated and
      complicated pregnancies of women with polycystic ovary syndrome.
AB  - OBJECTIVE: We studied a possible association between pregnancy complications and
      blood/serum levels of haemoglobin, C-reactive protein, sex hormones and lipids in
      women with polycystic ovary syndrome. MATERIAL AND METHODS: Twenty-one women with
      polycystic ovary syndrome were followed prospectively from the first trimester to
      delivery. Women with pregnancy complications (n=10) were compared to women
      without complications (n=11). Outcome measures were blood/serum levels of
      haemoglobin, C-reactive protein, dehydroepiandrosterone sulphate,
      androstenedione, testosterone, sex hormone binding globulin, free testosterone
      index, oestrogens and lipids. RESULTS: Haemoglobin levels were higher in
      complicated pregnancies compared to uncomplicated pregnancies throughout the
      complete pregnancy, while C-reactive protein levels were higher for complicated
      pregnancies at gestational weeks 19 and 32. Serum levels of lipids, androgens and
      oestrogens did not differ throughout pregnancy. CONCLUSION: In women suffering
      from polycystic ovary syndrome, pregnancy complications were associated with
      elevated blood/serum levels of haemoglobin and C-reactive protein. Androgen,
      oestrogen and lipid levels did not differ between groups.

PMID- 19172700
TI  - A genotyping method for VKORC1 1173C > T by Pyrosequencing technology.
AB  - Vitamin K epoxide reductase complex subunit 1 (VKORC1) is the site of inhibition
      by warfarin and other antivitamin K drugs during oral anticoagulant therapy. The
      SNP rs9934438 in intron 1 of VKORC1 (c.173+1000C > T or 1173C > T) discriminating
      the VKORC1*2 haplotype is associated with low warfarin dose requirement and
      unstable prothrombin time - international normalized ratio. To genotype this SNP,
      we have developed a rapid method using Pyrosequencing technology. The proposed
      method takes a post-PCR sample preparation of less than 1 h and a DNA sequencing
      time of less than 15 min to genotype 96 samples. The current method was compared
      with a dHPLC method that we reported previously. Genotype frequencies at VKORC1
      1173C>T for our Swedish population were 38% wild-type, 40% heterozygote and 22%
      homozygote. The frequency of the T-allele was 0.42, which exactly matches the
      frequency previously reported for Germans. The current method can be used to
      determine whether patients initiating warfarin therapy are carriers of SNP 1173
      C>T that is strongly associated with low warfarin dose requirement.

PMID- 19172701
TI  - Pre-metrological variation of immunological quantities.

PMID- 19172702
TI  - Expanding the horizons: new approaches to providing HIV testing services in the
      United States.

PMID- 19172703
TI  - Patient perceptions and acceptance of routine emergency department HIV testing.
AB  - OBJECTIVES: We report on the rates of patient acceptance and their perceptions of
      routine emergency department (ED) human immunodeficiency virus (HIV) testing in a
      high-prevalence area. METHODS: We analyzed the race/ethnicity of patients who
      either accepted or declined a routine HIV test that was offered to all patients
      in the ED of a large academic center. We also distributed a patient perception
      survey about ED HIV testing. RESULTS: During the study period, an HIV screening
      test was offered to 9,826 patients. Of these, 5,232 patients (53%) accepted the
      test. The acceptance rate of HIV testing was highest among African American
      patients (55%), followed by 52% for white, 50% for Hispanic, and 42% for Asian
      patients. A total of 1,519 completed surveys were returned for analysis. The most
      common reasons for declining a test were that patients did not perceive
      themselves to be at risk for HIV (49%) or they had recently been tested for HIV
      (18%). Overall, 84% of patients stated they would recommend to a friend to get an
      HIV test in the ED. When analyzed by ethnicity, 89% of African American patients
      stated they would recommend to a friend to get an HIV test if the friend went to
      the ED, but only 74% of white patients would do so. CONCLUSIONS: The Centers for
      Disease Control and Prevention's 2006 recommendations on HIV screening are well
      accepted by the target populations. Further work at explaining the risk of HIV
      infection to ED patients should be undertaken and may boost the acceptance rate
      of ED HIV screening.

PMID- 19172704
TI  - Emergency department patient acceptance of opt-in, universal, rapid HIV
      screening.
AB  - OBJECTIVES: We assessed emergency department (ED) patient acceptance of opt-in,
      rapid human immunodeficiency virus (HIV) screening and identified demographic
      characteristics and HIV testing-history factors associated with acceptance of
      screening. METHODS: A random sample of 18- to 55-year-old ED patients was offered
      rapid HIV screening. Patient acceptance or decline of screening and the reasons
      for acceptance or decline were analyzed with multivariable regression models.
      Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for the
      logistic regression models. RESULTS: Of the 2,099 participants, 39.3% accepted
      HIV screening. In a multinomial regression model, participants who were never
      married/not partnered, did not have private health insurance, and had 12 or fewer
      years of education were more likely to be screened due to concern about a
      possible HIV exposure. In a multivariable logistic regression model, the odds of
      accepting screening were greater among those who were younger than 40-years-old
      (OR=1.61, 95% CI 1.32, 2.00), nonwhite (OR=1.28, 95% CI 1.04, 1.58), not married
      (OR=1.82, 95% CI 1.44, 2.28), lacking private health insurance (OR=1.40, 95% CI
      1.13, 1.74), and who had 12 or fewer years of education (OR=1.43, 95% CI 1.16,
      1.75). Despite use of a standardized protocol, patient acceptance of screening
      varied by which research assistant asked them to be screened. Patients not
      previously tested for HIV who were white, married, and 45 years or older and who
      had private health insurance were more likely to decline HIV screening.
      CONCLUSIONS: In an opt-in, universal, ED HIV screening program, patient
      acceptance of screening varied by demography, which indicates that the impact of
      such screening programs will not be universal. Future research will need to
      determine methods of increasing uptake of ED HIV screening that transcend patient
      demographic characteristics, HIV testing history, and motivation for testing.

PMID- 19172705
TI  - Implementing rapid HIV testing in outreach and community settings: results from
      an advancing HIV prevention demonstration project conducted in seven U.S. cities.
AB  - OBJECTIVES: The goals of this project were to assess the feasibility of
      conducting rapid human immunodeficiency virus (HIV) testing in outreach and
      community settings to increase knowledge of HIV serostatus among groups
      disproportionately affected by HIV and to identify effective nonclinical venues
      for recruiting people in the targeted populations. METHODS: Community-based
      organizations (CBOs) in seven U.S. cities conducted rapid HIV testing in outreach
      and community settings, including public parks, homeless shelters, and bars.
      People with reactive preliminary positive test results received confirmatory
      testing, and people confirmed to be HIV-positive were referred to health-care and
      prevention services. RESULTS: A total of 23,900 people received rapid HIV
      testing. Of the 267 people (1.1%) with newly diagnosed HIV infection, 75%
      received their confirmatory test results and 64% were referred to care. Seventy
      six percent were from racial/ethnic minority groups, and 58% identified
      themselves as men who have sex with men, 72% of whom reported having multiple sex
      partners in the past year. Venues with the highest proportion of new HIV
      diagnoses were bathhouses, social service organizations, and needle-exchange
      programs. The acceptance rate for testing was 60% among sites collecting this
      information. CONCLUSIONS: Findings from this demonstration project indicate that
      offering rapid HIV testing in outreach and community settings is a feasible
      approach for reaching members of minority groups and people at high risk for HIV
      infection. The project identified venues that would be important to target and
      offered lessons that could be used by other CBOs to design and implement similar
      programs in the future.

PMID- 19172706
TI  - Trastuzumab treatment beyond  brain progression in HER2-  positive metastatic
      breast  cancer.

PMID- 19172707
TI  - Advancing HIV prevention demonstration projects: new strategies for a changing
      epidemic.

PMID- 19172708
TI  - ACP Journal Club. Applying evidence: what's the next action?

PMID- 19172709
TI  - ACP Journal Club. Rosuvastatin prevented major cardiovascular events in persons
      with elevated C-reactive protein.

PMID- 19172710
TI  - ACP Journal Club. Review: Tight glucose control reduces septicemia, but not
      death, and increases hypoglycemia in critically ill adults.

PMID- 19172711
TI  - ACP Journal Club. Review: Inhaled anticholinergics increase risk for major
      cardiovascular events in chronic obstructive pulmonary disease.

PMID- 19172712
TI  - ACP Journal Club. Tiotropium reduced exacerbations but not rate of FEV1 decline
      in patients with COPD using other respiratory medications.

PMID- 19172713
TI  - ACP Journal Club. Aspirin and/or antioxidants did not  prevent CV events in
      diabetes and  peripheral arterial disease.

PMID- 19172714
TI  - ACP Journal Club. Pioglitazone reduced liver injury and  improved fasting glucose
      in nonalcoholic  steatohepatitis without diabetes.

PMID- 19172715
TI  - ACP Journal Club.  Defibrillator therapy improved quality of  life in CHF;
      amiodarone did not.

PMID- 19172716
TI  - ACP Journal Club.  n-3 polyunsaturated fatty acids reduced  morbidity and
      mortality in chronic heart  failure.

PMID- 19172717
TI  - ACP Journal Club.  Laparoscopic surgery was more effective  than medical
      management for chronic  gastroesophageal reflux disease.

PMID- 19172718
TI  - ACP Journal Club.  Alteplase given 3 to 4.5 hours after stroke  reduced
      disability and improved global  outcome.

PMID- 19172719
TI  - ACP Journal Club. Immediate and delayed acupuncture  reduced frequency and pain
      intensity of  primary migraine or tension-type headaches.

PMID- 19172720
TI  - ACP Journal Club. Arthroscopic surgery added no benefit  to optimized physical
      and medical therapy  in knee osteoarthritis.

PMID- 19172721
TI  - [Is the incomplete disk prolapse without effect on the roots clinically
      misunderstood?].

PMID- 19172722
TI  - [Pathogenesis of migraine].

PMID- 19172724
TI  - [Extra payment to perform good work?].

PMID- 19172725
TI  - [Surgical techniques: interventions on the paranasal sinuses--endonasal paranasal
      sinus interventions II].

PMID- 19172726
TI  - Decision making during the  conception and career of CD4+ T cells.
AB  - The mechanisms by which thymocytes commit to becoming CD4+ T cells and how these
      cells subsequently can adopt various cell fates are becoming important paradigms
      of developmental programming. Understanding how such CD4+ T-cell diversity
      accommodates both immune reaction against various challenges and the suppression
      of undesirable responses is also revealing new therapeutic options.

PMID- 19172727
TI  - Prenatal and early postnatal morphogenesis and growth of human laryngotracheal
      structures.
AB  - Advances in neonatal medicine have resulted in increased care of fetal and
      neonatal airways. These advances have required an exhaustive knowledge of fetal
      airway anatomy and development. The aim of this study was to determine the
      anatomical development of laryngotracheal structures during the fetal and
      immediate postnatal period and to correlate these observations with other fetal
      biometric parameters to estimate developmental particularities of the fetal
      airway. An anatomical prospective study was based on examination of larynx and
      trachea from 300 routine autopsies of fetuses and infants, free of malformation
      and never intubated. Anatomical measurements of cricoid cartilage, thyroid
      cartilage, glottis, arytenoid cartilage and trachea were performed using a
      precision calliper and precision divider. Statistical analysis was performed to
      represent the growth of anatomical structures and to evaluate the correlation
      with biometric data. Raw data and 10th and 90th percentile curves were fitted
      satisfactorily with a linear model for gestational age. A linear relationship
      between laryngotracheal measurement and body weight and height was observed
      except for glottis length, interarytenoid distance and anterior cricoid height.
      The diameter of the cricoid lumen was significantly less than that of the trachea
      and glottis lumen. A sexual dysmorphism was noted for thyroid cartilage
      measurements and interarytenoid distance, with measurements significantly smaller
      in females. This study reports the anatomical development of normal
      laryngotracheal structures during the fetal period. Despite the fact that this
      study was performed during postmortem examination, these observations can be
      useful to develop criteria, materials and surgical procedures adapted to fetal
      and neonatal airways as well as for the purposes of early diagnosis and
      management of laryngotracheal malformations.

PMID- 19172729
TI  - The unusual orbitosphenoid of the snakelike lizard Bachia bicolor.
AB  - We studied the morphology of the chondrocranial orbitotemporal region in the
      snakelike gymnophthalmid lizard Bachia bicolor and its relation to other
      structures such as the ophthalmic division of the trigeminal nerve and eye
      muscles, to show its particular morphology, and discuss the homology of some
      skeletal structures relative to other squamates. We used three-dimensional
      computer reconstructions from serial histological sections; additionally we
      studied the embryonic and postembryonic development of the orbitosphenoid bone
      using cleared and double-stained whole-mount skeletal material. The
      chondrocranial orbitotemporal morphology in B. bicolor was found to be severely
      reduced as described for other miniaturized snakelike squamates, but it was
      accompanied by extensive orbitosphenoid ossifications. Within squamates, only
      amphisbaenians showed an expanded orbitosphenoid, which originates from fused
      endochondral and membranous ossifications. In B. bicolor the orbitosphenoid was
      also found to be formed by endochondral and membranous ossifications, but
      contrary to the amphisbaenian condition the membranous ossifications were found
      to arise as membrane bone outgrowths from the perichondral ossification of the
      chondral core. Despite its derived morphologies, we argue that the
      orbitosphenoids in amphisbaenians and B. bicolor are homologous to the
      orbitosphenoids of other squamates. Thus, the expanded orbitosphenoid morphology
      is found to be achieved by different ontogenetic processes in amphisbaenians and
      B. bicolor, representing a case of independent evolution by convergence.

PMID- 19172728
TI  - The vomeronasal organ of the tammar wallaby.
AB  - The vomeronasal organ is the primary olfactory organ that detects sexual
      pheromones in mammals. We investigated the anatomy of the vomeronasal organ of
      the tammar wallaby (Macropus eugenii), a small macropodid marsupial. Pheromones
      may be important for activation of the hypothalamo-pituitary axis of tammar males
      at the start of the breeding season because plasma testosterone and luteinizing
      hormone concentration in males rise concurrently with pregnancy and the post
      partum ovulation in females. The gross anatomy and the connection to the brain of
      the vomeronasal organ were examined by light and electron microscopy in adult
      male and female tammars. The vomeronasal organ was well developed in both sexes.
      The vomeronasal organ is a tubular organ connected at the rostral end via the
      nasopalatine duct (incisive duct) to the mouth and nasal cavity. At the rostral
      end the lumen of the vomeronasal organ was crescent shaped, changing to a narrow
      oval shape caudally. Glandular tissue associated with the vomeronasal organ
      increased towards the blind end of the organ. The tammar has the typical pattern
      of mammalian vomeronasal organs with electron-dense supporting cells and electron
      lucent receptor cells. Microvilli were present on the surface of both epithelia
      while cilia were only found on the surface of the non-receptor epithelium. Some
      non-receptor epithelial cells appeared to secrete mucus into the vomeronasal
      organ lumen. The vomeronasal organ shows a high degree of structural conservation
      compared with eutherian mammals. The degree of vomeronasal organ development
      makes it likely that, as in other mammals, pheromones are important in the
      reproduction of the tammar.

PMID- 19172730
TI  - Megadontia, striae periodicity and patterns of enamel secretion in Plio
      Pleistocene fossil hominins.
AB  - Early hominins formed large and thick-enamelled cheek-teeth within relatively
      short growth periods as compared with modern humans. To understand better the
      developmental basis of this process, we measured daily enamel increments, or
      cross striations, in 17 molars of Plio-Pleistocene hominins representing seven
      different species, including specimens attributed to early Homo. Our results show
      considerable variation across species, although all specimens conformed to the
      known pattern characterised by greater values in outer than inner enamel, and
      greater cuspal than cervical values. We then compared our results with the
      megadontia index, which represents tooth size in relation to body mass, for each
      species to assess the effect of daily growth rates on tooth size. Our results
      indicate that larger toothed (megadont) taxa display higher rates or faster
      forming enamel than smaller toothed hominins. By forming enamel quickly, large
      tooth crowns were able to develop within the constraints of shorter growth
      periods. Besides daily increments, many animals express long-period markings
      (striae of Retzius) in their enamel. We report periodicity values (number of
      cross striations between adjacent striae) in 14 new specimens of Australopithecus
      afarensis, Paranthropus aethiopicus, Paranthropus boisei, Homo habilis, Homo
      rudolfensis and Homo erectus, and show that long-period striae express a strong
      association with male and average male-female body mass. Our results for Plio
      Pleistocene hominins show that the biological rhythms that give rise to long
      period striae are encompassed within the range of variation known for modern
      humans, but show a lower mean and modal value of 7 days in australopithecines. In
      our sample of early Homo, mean and modal periodicity values were 8 days, and
      therefore similar to modern humans. These new data on daily rates of enamel
      formation and periodicity provide a better framework to interpret surface
      manifestations of internal growth markings on fossil hominin tooth crowns.
      Importantly, our data on early hominin cross striation variation may now
      contribute towards solving difficult taxonomic diagnoses where much may depend on
      fragmentary molar remains and enamel structure.

PMID- 19172731
TI  - The distal forelimb musculature in aquatic and terrestrial turtles: phylogeny or
      environmental constraints?
AB  - We compared the muscular anatomy of the distal front limb in terrestrial and
      aquatic chelonians to test whether observed differences between the two groups
      are associated with their divergent lifestyles and locomotor modes. Given the
      different use of the forelimb in the two environments (body support and
      propulsion on land vs. mainly propulsion in water) we expected that: (1) aquatic
      and terrestrial turtles would show differences in their muscular anatomy, with
      aquatic species having more individualized muscle bundlesto allow for the complex
      forearm movements observed during swimming, and (2) that terrestrial turtles
      would have more robust muscles to support their body weight against gravity. To
      address these questions, we examined the forelimb myology and associated tissues
      in six aquatic or semi-aquatic turtles (Phyrnops hilarii, Podocnemis unifilis,
      Trachemys scripta, Sacalia bealei, Cuora amboinensis and Mauremys caspica) and
      six terrestrial or semi-terrestrial turtles (Geochelone chilensis, Testudo
      graeca, Cuora galbinifrons, Glyptemys insculpta, Terrapene carolina and
      Rhinoclemmys pulcherrima). This paper describes the general structure of the
      forelimb musculature in all species, and quantifies muscle masses in those
      species with more than five specimens available (Ph. hilarii, Po. unifilis and
      Ge. chilensis). The general structure of the forelimb muscles in the strictly
      terrestrial species Ge. chilensis and Tes. graeca was found to be notably
      different from the pattern of the aquatic and semi-aquatic species examined,
      showing a distinct fusion of the different muscular bodies. Ter. carolina also
      show a distinctly terrestrial pattern, but a less extensive tendon development.
      R. pulcherrima and GI. insculpta were found to be morphologically intermediate;
      in the geoemydids the strictly terrestrial bauplan never appears. Quantitative
      differences in the robustness or mass of the distal forelimb muscles were also
      observed for the species investigated, supporting our prediction that the
      extensor muscles are more robust in terrestrial turtles. However, in contrast to
      our expectations, not only the extensor muscles of the distal forelimb (which are
      crucial in providing both body support and propulsion), but all muscles acting
      around the wrist were found to be heavier in terrestrial turtles.

PMID- 19172732
TI  - Abdominal muscle size and symmetry at rest and during abdominal hollowing
      exercises in healthy control subjects.
AB  - The symmetry of, and physical characteristics influencing, the thickness of the
      lateral abdominal muscles at rest and during abdominal exercises were examined in
      57 healthy subjects (20 men, 37 women; aged 22-62 years). M-mode ultrasound
      images were recorded from the abdominal muscles at rest and during abdominal
      hollowing exercises in hook-lying. The fascial lines bordering the transvs.
      abdominis, obliquus internus and obliquus externus were digitized and the
      absolute thickness, relative thickness (% of total lateral thickness) and
      contraction ratio (thickness during hollowing/thickness at rest), as well as the
      asymmetry (difference between sides expressed as a percent of the smallest value
      for the two sides) for each of these parameters were determined for each muscle.
      Both at rest and during hollowing, obliquus internus was the thickest and
      transvs. abdominis the thinnest muscle. There were no significant differences
      between left and right sides for group mean thicknesses of any muscle; however,
      individual asymmetries were evident, with mean values for the different muscles
      ranging from 11% to 26%; asymmetry was much less for the contraction ratios (mean
      % side differences, 5-14% depending on muscle). Body mass was the most
      significant positive predictor of absolute muscle thickness, for all muscles at
      rest and during hollowing, accounting for 30-44% variance. Body mass index
      explained 20-30% variance in transvs. abdominis contraction ratio (negative
      relationship). The influence of these confounders must be considered in
      comparative studies of healthy controls and back pain patients, unless groups are
      very carefully matched. Asymmetries observed in patients should be interpreted
      with caution, as they are also common in healthy subjects.

PMID- 19172733
TI  - A model of the intracortical vascular system of long bones and of its
      organization: an experimental study in rabbit femur and tibia.
AB  - The vascular anatomy of the cortical bone and the canal system are highly
      correlated, and the former has an important bearing on shape and microscopic
      lamellar structure, as it is established in the progression of the remodelling
      process. The classical description of a longitudinal system of canals (Havers')
      connected by the transversal Volkmann's canals is the generally acknowledged
      model of the structural organization of the cortex. However, it is remarkably
      difficult to study the circulation inside the compact bone in detail owing to its
      hard, calcified matrix, and the methods thus far applied have represented either
      the bone morphology and the architecture of the canal system or the injected
      vessel network. In the present study, the intracortical vessel network was
      injected with black China ink and evidenced by transillumination of full
      thickness, decalcified hemicortices. By making use of the depth of field of the
      microscope objective, the three-dimensional architecture of the network was
      highlighted and the morphometry of vessel size measurements and a classification
      of the network nodes according to the number of arms was made possible. These
      observations were integrated with data obtained by routine histology on
      decalcified sections relevant to the connections of the intracortical canal
      system with the outer environment, with regard to the direction of advancement of
      new canals and with regard to the mode of formation of the system nodes. The
      formation of the intracortical vessels network involved two processes: the
      incorporation of the periosteal network and osteonal remodelling, the latter
      occurring through the advancement of cutting cones followed by their own vascular
      loop and by concentric lamellar apposition. The two systems could be
      distinguished by the diameter of the vessels (the former were significantly
      larger) and by the network architecture (the former convoluted, and the latter
      longitudinally orientated and straight). Longitudinal vessels could form branches
      or create connections with the periosteal derived vessels that occasionally meet
      on the line of their advancement. They were observed entering from either inside
      the cortex from the metaphyses or from the endosteal surface of the marrow
      cavity. The combined observations from different methods of study documented a
      model of intracortical canal and vessel networks formed by two initially
      independent systems: one derived from the external, periosteal vessels, and one
      from metaphyseal and marrow vessels. Connections between the two were established
      with the advancing of cutting cones from the extremities of the diaphysis.
      Analysis of the system architecture and the modalities of its progressive
      organization suggested that the direction of advancement of a forming canal does
      not necessarily correspond to the final blood flow direction of its central
      vessel.

PMID- 19172734
TI  - Identification and characterization of a novel intraepithelial lymphoid tissue in
      the gills of Atlantic salmon.
AB  - In addition to being the respiratory organ in fish, the gills form a barrier
      against the external milieu. Innate and adaptive immune system components have
      been detected in the gills, but lymphoid cell accumulations similar to that seen
      in the mammalian mucosa have not been described. The present investigations
      revealed cell accumulations on the caudal edge of interbranchial septum at the
      base of the gill filaments in the Atlantic salmon. Cytokeratin
      immunohistochemical staining and identification of a basal membrane and desmosome
      cell junctions by electron microscopy showed that the cell accumulation was
      located intraepithelially. Major histocompatibility complex (MHC) class II+ cells
      were detected by immunohistochemistry, and laser capture micro-dissection and
      subsequent RT-PCR analysis revealed expression of T-cell receptor transcripts in
      the investigated tissue, suggesting the presence of T cells. The intraepithelial
      tissue reported here may be a suitable location for immune surveillance of gill
      infections, as well as a target site for new vaccine approaches and
      investigations of epithelial immunity. This is the first description of a
      lymphocyte cell aggregation within a teleostian gill epithelium network,
      illustrating a phylogenetically early form of leukocyte accumulations in a
      respiratory organ.

PMID- 19172735
TI  - Anatomy of the nasal profile.
AB  - There is a lack in the understanding of the variation within the thickness of the
      soft tissue structures (muscle, skin and fat) overlying the cartilaginous
      skeleton of the nose and their relationship to the dorsum shape. We examined such
      relationships by dissecting noses of six adult female and six adult male
      cadavers, comparing the internal anatomical structures to the external nasal
      profile. We found that the soft tissue structures differ in thickness along the
      dorsum and that these differences are individualized. Specifically, continuous
      presence of subcutaneous fat from root to tip was found in half the sample, one
      nose had fat only on the tip, another one only on the root, the four others at
      both positions. The nasalis muscle was identifiable in nine of the 12 noses,
      transversing the nose in half the sample, and in the remaining three, only the
      lateral section of the muscle was identified. The superior border of the septal
      cartilage does not form a linear extension of the profile contour of the nasal
      bones but angles downwards. The actual profile contour of the dorsum does not
      follow the profile of the nasal bones or the septal cartilage. These results may
      influence the current use of nasal guidelines in forensic facial approximation.

PMID- 19172736
TI  - High-resolution visualization of airspace structures in intact mice via
      synchrotron phase-contrast X-ray imaging (PCXI).
AB  - Anatomical visualization of airspace-containing organs in intact small animals
      has been limited by the resolution and contrast available from current imaging
      methods such as X-ray, micro-computed tomography and magnetic resonance imaging.
      Determining structural relationships and detailed anatomy has therefore relied on
      suitable fixation, sectioning and histological processing. More complex and
      informative analyses such as orthogonal views of an organ and three-dimensional
      structure visualizations have required different animals and image sets,
      laboriously processed to gather this complementary structural information.
      Precise three-dimensional anatomical views have always been difficult to achieve
      in small animals. Here we report the ability of phase-contrast synchrotron X-ray
      imaging to provide detailed two- and three-dimensional visualization of airspace
      organ structures in intact animals. Using sub-micrometre square pixel charge
      coupled device array detectors, the structure and anatomy of hard and soft
      tissues, and of airspaces, is readily available using phase-contrast synchrotron
      X-ray imaging. Moreover, software-controlled volume-reconstructions of
      tomographic images not only provide unsurpassed image clarity and detail, but
      also selectable anatomical views that cannot be obtained with established
      histological techniques. The morphology and structure of nasal and lung airways
      and the middle ear are illustrated in intact mice, using two- and three
      dimensional representations. The utility of phase-contrast synchrotron X-ray
      imaging for noninvasively localizing objects implanted within airspaces, and the
      detection of gas bubbles transiting live airways, are other novel features of
      this visualization methodology. The coupling of phase-contrast synchrotron X-ray
      imaging technology with software-based reconstruction techniques holds promise
      for novel and high-resolution non-invasive examination of airspace anatomy in
      small animal models.

PMID- 19172737
TI  - Delta6-desaturase (FADS2) deficiency unveils the role of omega3- and omega6
      polyunsaturated fatty acids.
AB  - Mammalian cell viability is dependent on the supply of the essential fatty acids
      (EFAs) linoleic and alpha-linolenic acid. EFAs are converted into omega3- and
      omega6-polyunsaturated fatty acids (PUFAs), which are essential constituents of
      membrane phospholipids and precursors of eicosanoids, anandamide and docosanoids.
      Whether EFAs, PUFAs and eicosanoids are essential for cell viability has remained
      elusive. Here, we show that deletion of delta6-fatty acid desaturase (FADS2) gene
      expression in the mouse abolishes the initial step in the enzymatic cascade of
      PUFA synthesis. The lack of PUFAs and eicosanoids does not impair the normal
      viability and lifespan of male and female fads2 -/- mice, but causes sterility.
      We further provide the molecular evidence for a pivotal role of PUFA-substituted
      membrane phospholipids in Sertoli cell polarity and blood-testis barrier, and the
      gap junction network between granulosa cells of ovarian follicles. The fads2 -/-
      mouse is an auxotrophic mutant. It is anticipated that FADS2 will become a major
      focus in membrane, haemostasis, inflammation and atherosclerosis research.

PMID- 19172738
TI  - Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2
      docking protein.
AB  - Grb2-associated binder (Gab)2 functions downstream of a variety of receptor and
      cytoplasmic tyrosine kinases as a docking platform for specific signal
      transducers and performs important functions in both normal physiology and
      oncogenesis. Gab2 signalling is promoted by its association with specific
      receptors through the adaptor Grb2. However, the molecular mechanisms that
      attenuate Gab2 signals have remained unclear. We now demonstrate that growth
      factor-induced phosphorylation of Gab2 on two residues, S210 and T391, leads to
      recruitment of 14-3-3 proteins. Together, these events mediate negative-feedback
      regulation, as Gab2(S210A/T391A) exhibits sustained receptor association and
      signalling and promotes cell proliferation and transformation. Importantly,
      introduction of constitutive 14-3-3-binding sites into Gab2 renders it refractory
      to receptor activation, demonstrating that site-selective binding of 14-3-3
      proteins is sufficient to terminate Gab2 signalling. Furthermore, this is
      associated with reduced binding of Grb2. This leads to a model where signal
      attenuation occurs because 14-3-3 promotes dissociation of Gab2 from Grb2, and
      thereby uncouples Gab2 from the receptor complex. This represents a novel
      regulatory mechanism with implications for diverse tyrosine kinase signalling
      systems.

PMID- 19172739
TI  - Distinct roles for yeast Stn1 in telomere capping and telomerase inhibition.
AB  - The budding yeast Cdc13, Stn1 and Ten1 (CST) proteins are proposed to function as
      an RPA-like complex at telomeres that protects ('caps') chromosome ends and
      regulates their elongation by telomerase. We show that Stn1 has a critical
      function in both processes through the deployment of two separable domains. The N
      terminus of Stn1 interacts with Ten1 and carries out its essential capping
      function. The C terminus of Stn1 binds both Cdc13 and Pol12, and we present
      genetic data indicating that the Stn1-Cdc13 interaction is required to limit
      continuous telomerase action. Stn1 telomere association, similar to that of
      Cdc13, peaks during S phase. Significantly, the magnitude of Stn1 telomere
      binding is independent of telomere TG tract length, suggesting that the negative
      effect of Stn1 on telomerase action might be regulated by a modification of CST
      activity or structure in cis at individual telomeres. Genetic analysis suggests
      that the Tell kinase exerts an effect in parallel with the Stn1 C terminus to
      counteract its inhibition of telomerase. These data provide new insights into the
      coordination of telomere capping and telomerase regulation.

PMID- 19172740
TI  - Structure of the archaeal Kae1/Bud32 fusion protein MJ1130: a model for the
      eukaryotic EKC/KEOPS subcomplex.
AB  - The EKC/KEOPS yeast complex is involved in telomere maintenance and
      transcription. The Bud32p and kinase-associated endopeptidase 1 (Kaelp)
      components of the complex are totally conserved in eukarya and archaea. Their
      genes are fused in several archaeal genomes, suggesting that they physically
      interact. We report here the structure of the Methanocaldococcus jannaschii
      Kae1/Bud32 fusion protein MJ1130. Kae1 is an iron protein with an ASKHA fold and
      Bud32 is an atypical small RIO-type kinase. The structure MJ1130 suggests that
      association with Kae1 maintains the Bud32 kinase in an inactive state. We indeed
      show that yeast Kae1p represses the kinase activity of yeast Bud32p. Extensive
      conserved interactions between MjKae1 and MjBud32 suggest that Kae1p and Bud32p
      directly interact in both yeast and archaea. Mutations that disrupt the
      Kae1p/Bud32p interaction in the context of the yeast complex have dramatic
      effects in vivo and in vitro, similar to those observed with deletion mutations
      of the respective components. Direct interaction between Kae1p and Bud32p in
      yeast is required both for the transcription and the telomere homeostasis
      function of EKC/KEOPS.

PMID- 19172742
TI  - Primary microRNA transcripts are processed co-transcriptionally.
AB  - microRNAs (miRNAs) are generated from long primary (pri-) RNA polymerase II (Pol
      II)-derived transcripts by two RNase III processing reactions: Drosha cleavage of
      nuclear pri-miRNAs and Dicer cleavage of cytoplasmic pre-miRNAs. Here we show
      that Drosha cleavage occurs during transcription acting on both independently
      transcribed and intron-encoded miRNAs. We also show that both 5'-3' and 3'-5'
      exonucleases associate with the sites where co-transcriptional Drosha cleavage
      occurs, promoting intron degradation before splicing. We finally demonstrate that
      miRNAs can also derive from 3' flanking transcripts of Pol II genes. Our results
      demonstrate that multiple miRNA-containing transcripts are co-transcriptionally
      cleaved during their synthesis and suggest that exonucleolytic degradation from
      Drosha cleavage sites in pre-mRNAs may influence the splicing and maturation of
      numerous mRNAs.

PMID- 19172743
TI  - A new tRNA intermediate revealed on the ribosome during EF4-mediated back
      translocation.
AB  - EF4 (LepA) is an almost universally conserved translational GTPase in eubacteria.
      It seems to be essential under environmental stress conditions and has previously
      been shown to back-translocate the tRNAs on the ribosome, thereby reverting the
      canonical translocation reaction. In the current work, EF4 was directly
      visualized in the process of back-translocating tRNAs by single-particle cryo-EM.
      Using flexible fitting methods, we built a model of ribosome-bound EF4 based on
      the cryo-EM map and a recently published unbound EF4 X-ray structure. The cryo-EM
      map establishes EF4 as a noncanonical elongation factor that interacts not only
      with the elongating ribosome, but also with the back-translocated tRNA in the A
      site region, which is present in a previously unseen, intermediate state and
      deviates markedly from the position of a canonical A-tRNA. Our results,
      therefore, provide insight into the underlying structural principles governing
      back-translocation.

PMID- 19172744
TI  - SRP RNA controls a conformational switch regulating the SRP-SRP receptor
      interaction.
AB  - The interaction of the signal-recognition particle (SRP) with its receptor (SR)
      mediates co-translational protein targeting to the membrane. SRP and SR interact
      via their homologous core GTPase domains and N-terminal four-helix bundles (N
      domains). SRP-SR complex formation is slow unless catalyzed by SRP's essential
      RNA component. We show that truncation of the first helix of the N domain (helix
      N1) of both proteins dramatically accelerates their interaction. SRP and SR with
      helix N1 truncations interact at nearly the RNA-catalyzed rate in the absence of
      RNA. NMR spectroscopy and analysis of GTPase activity show that helix N1
      truncation in SR mimics the conformational switch caused by complex formation.
      These results demonstrate that the N-terminal helices of SRP and SR are
      autoinhibitory for complex formation in the absence of SRP RNA, suggesting a
      mechanism for RNA-mediated coordination of the SRP-SR interaction.

PMID- 19172745
TI  - Structural basis for the activation of PPARgamma by oxidized fatty acids.
AB  - The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma)
      has important roles in adipogenesis and immune response as well as roles in both
      lipid and carbohydrate metabolism. Although synthetic agonists for PPARgamma are
      widely used as insulin sensitizers, the identity of the natural ligand(s) for
      PPARgamma is still not clear. Suggested natural ligands include 15-deoxy
      delta12,14-prostaglandin J2 and oxidized fatty acids such as 9-HODE and 13-HODE.
      Crystal structures of PPARgamma have revealed the mode of recognition for
      synthetic compounds. Here we report structures of PPARgamma bound to oxidized
      fatty acids that are likely to be natural ligands for this receptor. These
      structures reveal that the receptor can (i) simultaneously bind two fatty acids
      and (ii) couple covalently with conjugated oxo fatty acids. Thermal stability and
      gene expression analyses suggest that such covalent ligands are particularly
      effective activators of PPARgamma and thus may serve as potent and biologically
      relevant ligands.

PMID- 19172747
TI  - Structural basis of enzyme encapsulation into a bacterial nanocompartment.
AB  - Compartmentalization is an important organizational feature of life. It occurs at
      varying levels of complexity ranging from eukaryotic organelles and the bacterial
      microcompartments, to the molecular reaction chambers formed by enzyme
      assemblies. The structural basis of enzyme encapsulation in molecular
      compartments is poorly understood. Here we show, using X-ray crystallographic,
      biochemical and EM experiments, that a widespread family of conserved bacterial
      proteins, the linocin-like proteins, form large assemblies that function as a
      minimal compartment to package enzymes. We refer to this shell-forming protein as
      'encapsulin'. The crystal structure of such a particle from Thermotoga maritima
      determined at 3.1-angstroms resolution reveals that 60 copies of the monomer
      assemble into a thin, icosahedral shell with a diameter of 240 angstroms. The
      interior of this nanocompartment is lined with conserved binding sites for short
      polypeptide tags present as C-terminal extensions of enzymes involved in
      oxidative-stress response.

PMID- 19172746
TI  - Structure of the DBL3x domain of pregnancy-associated malaria protein VAR2CSA
      complexed with chondroitin sulfate A.
AB  - Plasmodium falciparum-infected erythrocytes bind to chondroitin sulfate A (CSA)
      in the placenta via the VAR2CSA protein, a member of the P. falciparum
      erythrocyte membrane protein-1 family, leading to life-threatening malaria in
      pregnant women with severe effects on their fetuses and newborns. Here we
      describe the structure of the CSA binding DBL3x domain, a Duffy binding-like
      (DBL) domain of VAR2CSA. By forming a complex of DBL3x with CSA oligosaccharides
      and determining its structure, we have identified the CSA binding site to be a
      cluster of conserved positively charged residues on subdomain 2 and subdomain 3.
      Mutation or chemical modification of lysine residues at the site markedly
      diminished CSA binding to DBL3x. The location of the CSA binding site is an
      important step forward in the molecular understanding of pregnancy-associated
      malaria and offers a new target for vaccine development.

PMID- 19172748
TI  - Molecular functions of the histone acetyltransferase chaperone complex Rtt109
      Vps75.
AB  - Histone acetylation and nucleosome remodeling regulate DNA damage repair,
      replication and transcription. Rtt109, a recently discovered histone
      acetyltransferase (HAT) from Saccharomyces cerevisiae, functions with the histone
      chaperone Asf1 to acetylate lysine K56 on histone H3 (H3K56), a modification
      associated with newly synthesized histones. In vitro analysis of Rtt109 revealed
      that Vps75, a Nap1 family histone chaperone, could also stimulate Rtt109
      dependent acetylation of H3K56. However, the molecular function of the Rtt109
      Vps75 complex remains elusive. Here we have probed the molecular functions of
      Vps75 and the Rtt109-Vps75 complex through biochemical, structural and genetic
      means. We find that Vps75 stimulates the kcat of histone acetylation by
      approximately 100-fold relative to Rtt109 alone and enhances acetylation of K9 in
      the H3 histone tail. Consistent with the in vitro evidence, cells lacking Vps75
      showed a substantial reduction (60%) in H3K9 acetylation during S phase. X-ray
      structural, biochemical and genetic analyses of Vps75 indicate a unique,
      structurally dynamic Nap1-like fold that suggests a potential mechanism of Vps75
      dependent activation of Rttl09. Together, these data provide evidence for a
      multifunctional HAT-chaperone complex that acetylates histone H3 and deposits H3
      H4 onto DNA, linking histone modification and nucleosome assembly.

PMID- 19172749
TI  - Histone chaperone specificity in Rtt109 activation.
AB  - Rtt109 is a histone acetyltransferase that requires a histone chaperone for the
      acetylation of histone 3 at lysine 56 (H3K56). Rtt109 forms a complex with the
      chaperone Vps75 in vivo and is implicated in DNA replication and repair. Here we
      show that both Rtt109 and Vps75 bind histones with high affinity, but only the
      complex is efficient for catalysis. The C-terminal acidic domain of Vps75
      contributes to activation of Rtt109 and is necessary for in vivo functionality of
      Vps75, but it is not required for interaction with either Rtt109 or histones. We
      demonstrate that Vps75 is a structural homolog of yeast Nap1 by solving its
      crystal structure. Nap1 and Vps75 interact with histones and Rtt109 with
      comparable affinities. However, only Vps75 stimulates Rtt109 enzymatic activity.
      Our data highlight the functional specificity of Vps75 in Rtt109 activation.

PMID- 19172751
TI  - The HP1-p150/CAF-1 interaction is required for pericentric heterochromatin
      replication and S-phase progression in mouse cells.
AB  - The heterochromatin protein 1 (HP1)-rich heterochromatin domains next to
      centromeres are crucial for chromosome segregation during mitosis. This mitotic
      function requires their faithful reproduction during the preceding S phase, a
      process whose mechanism and regulation are current puzzles. Here we show that
      p150, a subunit of chromatin assembly factor 1, has a key role in the replication
      of pericentric heterochromatin and S-phase progression in mouse cells,
      independently of its known function in histone deposition. By a combination of
      depletion and complementation assays in vivo, we link this unique function of
      p150 to its ability to interact with HP1. Absence of this functional interaction
      triggers S-phase arrest at the time of replication of pericentromeric
      heterochromatin, without eliciting known DNA-based checkpoint pathways. Notably,
      in cells lacking the histone methylases Suv39h, in which pericentric domains do
      not show HP1 accumulation, p150 is dispensable for S-phase progression.

PMID- 19172750
TI  - A regulatable switch mediates self-association in an immunoglobulin fold.
AB  - Beta-2 microglobulin (beta2m) is a globular protein that self-associates into
      fibrillar amyloid deposits in patients undergoing hemodialysis therapy. Formation
      of these beta-sheet-rich assemblies is a fundamental property of polypeptides
      that can be triggered by diverse conditions. For beta2m, oligomerization into pre
      amyloidogenic states occurs in specific response to coordination by Cu2+. Here we
      report the basis for this self-association at atomic resolution. Metal is not a
      direct participant in the molecular interface. Rather, binding results in distal
      alterations enabling the formation of two new surfaces. These interact to form a
      closed hexameric species. The origins of this include isomerization of a buried
      and conserved cis-proline previously implicated in the beta2m aggregation
      pathway. The consequences of this isomerization are evident and reveal a
      molecular basis for the conversion of this robust monomeric protein into an
      amyloid-competent state.

PMID- 19172752
TI  - Structural basis for group A trichothiodystrophy.
AB  - Patients with the rare neurodevelopmental repair syndrome known as group A
      trichothiodystrophy (TTD-A) carry mutations in the gene encoding the p8 subunit
      of the transcription and DNA repair factor TFIIH. Here we describe the crystal
      structure of a minimal complex between Tfb5, the yeast ortholog of p8, and the C
      terminal domain of Tfb2, the yeast p52 subunit of TFIIH. The structure revealed
      that these two polypeptides adopt the same fold, forming a compact
      pseudosymmetric heterodimer via a beta-strand addition and coiled coils
      interactions between terminal alpha-helices. Furthermore, Tfb5 protects a
      hydrophobic surface in Tfb2 from solvent, providing a rationale for the influence
      of p8 in the stabilization of p52 and explaining why mutations that weaken p8-p52
      interactions lead to a reduced intracellular TFIIH concentration and a defect in
      nucleotide-excision repair, a common feature of TTD cells.

PMID- 19172753
TI  - A proposed OB-fold with a protein-interaction surface in Candida albicans
      telomerase protein Est3.
AB  - Ever shorter telomeres 3 (Est3) is an essential telomerase regulatory subunit
      thought to be unique to budding yeasts. Here we use multiple sequence alignment
      and hidden Markov model-hidden Markov model (HMM-HMM) comparison to uncover
      potential similarities between Est3 and the mammalian telomeric protein Tpp1.
      Analysis of site-specific mutants of Candida albicans Est3 revealed functional
      distinctions between residues that are conserved between Est3 and Tpp1 and those
      that are unique to Est3. Although both types of residues are important for
      telomere maintenance in vivo, only the former contributes to telomerase activity
      in vitro and facilitates the association of Est3 with telomerase core components.
      Consistent with a function in protein-protein interaction, the residues common to
      Est3 and Tpp1 map to one face of an OB-fold model structure, away from the
      canonical nucleic acid binding surface. We propose that Est3 and the OB-fold
      domain of Tpp1 mediate a conserved function in telomerase regulation.

PMID- 19172754
TI  - The Est3 protein associates with yeast telomerase through an OB-fold domain.
AB  - The Ever shorter telomeres 3 (Est3) protein is a small regulatory subunit of
      yeast telomerase which is dispensable for enzyme catalysis but essential for
      telomere replication in vivo. Using structure prediction combined with in vivo
      characterization, we show here that Est3 consists of a predicted OB
      (oligosaccharide/oligonucleotide binding)-fold. We used mutagenesis of predicted
      surface residues to generate a functional map of one surface of Est3, identifying
      a site that mediates association with the telomerase complex. Unexpectedly, the
      predicted OB-fold of Est3 is structurally similar to the OB-fold of the human
      TPP1 protein, despite the fact that Est3 and TPP1, as components of telomerase
      and a telomere-capping complex, respectively, perform functionally distinct tasks
      at chromosome ends. Our analysis of Est3 may be instructive in generating
      comparable missense mutations on the surface of the OB-fold domain of TPP1.

PMID- 19172755
TI  - [[Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, etc. The world renouned steer Sunny Boy].

PMID- 19172756
TI  - Epilepsy and respiratory chain defects in children with mitochondrial
      encephalopathies.

PMID- 19172757
TI  - The novel iron chelator, 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone,
      reduces catecholamine-mediated myocardial toxicity.
AB  - Iron (Fe) chelators are used clinically for the treatment of Fe overload disease.
      Iron also plays a role in the pathology of many other conditions, and these
      potentially include the cardiotoxicity induced by catecholamines such as
      isoprenaline (ISO). The current study examined the potential of Fe chelators to
      prevent ISO cardiotoxicity. This was done as like other catecholamines, ISO
      contains the classical catechol moiety that binds Fe and may form redox-active
      and cytotoxic Fe complexes. Studies in vitro used the cardiomyocyte cell line,
      H9c2, which was treated with ISO in the presence or absence of the chelator,
      desferrioxamine (DFO), or the lipophilic ligand, 2-pyridylcarboxaldehyde 2
      thiophenecarboxyl hydrazone (PCTH). Both of these chelators were not cardiotoxic
      and significantly reduced ISO cardiotoxicity in vitro. However, PCTH was far more
      effective than DFO, with the latter showing activity only at a high, clinically
      unachievable concentration. Further studies in vitro showed that interaction of
      ISO with Fe(II)/(III) did not increase cytotoxic radical generation, suggesting
      that this mechanism was not involved. Studies in vivo were initiated using rats
      pretreated intravenously with DFO or PCTH before subcutaneous administration of
      ISO (100 mg/kg). DFO at a clinically used dose (50 mg/kg) failed to reduce
      catecholamine cardiotoxicity, while PCTH at an equimolar dose totally prevented
      catecholamine-induced mortality and reduced cardiotoxicity. This study
      demonstrates that PCTH reduced ISO-induced cardiotoxicity in vitro and in vivo,
      demonstrating that Fe plays a role, in part, in the pathology observed.

PMID- 19172758
TI  - Retraction notice to "Synthesis, kinetic studies and pharmacological evaluation
      of mutual azo prodrug of 5-aminosalicylic acid for colon-specific drug delivery
      in inflammatory bowel disease" [European Journal of Medicinal Chemistry 42 (2006)
      885-890].

PMID- 19172759
TI  - Intracistronic transcriptional polarity enhances translational repression: a new
      role for Rho.
AB  - Transcriptional polarity in Escherichia coli occurs when cryptic Rho-dependent
      transcription terminators become activated as a consequence of reduced
      translation. Whether this is due to an increased spacing between the RNA
      polymerase and the leading ribosome or to prior functional inactivation of a
      subpopulation of the mRNAs has been a matter of discussion. Transcriptional
      polarity results in decreased synthesis of inefficiently translated mRNAs and
      therefore in decreased expression of downstream genes in the same operon
      (intercistronic polarity). By analogy, expression of the gene in which the
      conditional termination occurs is also expected to decrease, but this has so far
      not been demonstrated experimentally. To study the relevance of this
      intracistronic polarity for expression regulation in vivo, the polarity-prone
      IacZ reporter gene was fused to a range of mutated ribosome binding sites,
      repressed to different degrees by local RNA structure. Quantitative analysis of
      protein and mRNA synthesis shows that polarity occurs on functionally active mRNA
      molecules and that it indeed affects expression of the cistron carrying the
      terminator, thus enhancing the effect of translational repression. These findings
      point to a novel regulatory function of transcriptional polarity, reminiscent of
      transcriptional attenuation but opposite in effect.

PMID- 19172760
TI  - Measuring how fat we are.  Weighing the pros and cons of three measures of
      adiposity.

PMID- 19172761
TI  - Do PPIs have long-term side effects? Nexium and the other proton-pump inhibitors
      are great at reducing stomach acid, but that might have some unintended
      consequences.

PMID- 19172762
TI  - Changing the cardiovascular prevention game. Results from a large clinical trial
      may mean a new era of super-low LDL targets and anti-inflammatory strategies.

PMID- 19172763
TI  - Selenium for prostate cancer prevention.

PMID- 19172764
TI  - Masseteric nerve block for masseter muscle pain--a clinical note.
AB  - This article describes a technique for the delivery of local anesthetic to the
      masseteric nerve just before it innervates the masseter muscle. As the mandibular
      division (V3) of the trigeminal nerve exits foramen ovale, the anterior division
      of V3 along with the masseteric nerve travels in the infratemporal fossa.
      Eventually, the masseteric nerve passes through the mandibular notch to innervate
      the masseter muscle. With the aid of a cadaveric dissection, an infiltration
      technique for the regional blockade of the masseter muscle was devised. The
      masseteric nerve block is an effective technique for obtaining anesthesia in the
      whole masseter muscle. This peripheral nerve block provides another modality for
      the treatment of acute and chronic masseter muscle pain. The masseteric nerve
      block can also be used diagnostically to verify the source of pain.

PMID- 19172765
TI  - Lazy, apathetic and dangerous: the social construction of unemployed workers in
      Germany during the late Weimar Republic.

PMID- 19172766
TI  - Feminism as if all people mattered: working to remove the causes of war, 1919
      1929.

PMID- 19172767
TI  - From camp follower to lady in uniform: women, class and military institutions
      before 1920.

PMID- 19172768
TI  - The sacred in the scientific: ambiguous practices of science in Tibetan medicine.

PMID- 19172769
TI  - "Empty cradles" and the quiet revolution: demographic discourse and cultural
      struggles of gender, race, and class in Italy.

PMID- 19172770
TI  - "Making place" at the United Nations: indigenous cultural politics at the U.N.
      Working Group on Indigenous Populations.

PMID- 19172772
TI  - Protective effect of catechin on ischemia-reperfusion-induced renal injury in
      rats.

PMID- 19172771
TI  - Languages of sex and AIDS in Nepal: notes on the social production of
      commensurability.

PMID- 19172773
TI  - Early termination of pregnancy.

PMID- 19172774
TI  - Proceedings and abstracts of a conference on diagnostics of human viral blood
      borne infections, challenges and hopes in the 21st century, Zegrze, 23-24 October
      2008.

PMID- 19172775
TI  - [Madam's powder: tracing the history of magnetic cures for wounds in France].

PMID- 19172776
TI  - [Moliere's Femmes Savantes and the question of the functions of knowledge].

PMID- 19172778
TI  - Comment on Demirbag, et al. "Multidrug resistance of isolated microorganisms in
      occluded bile duct stents" (Turk J Gastroenterol 2007; 18 (1): 33-40).

PMID- 19172779
TI  - The socio-economic impact of regime change in eastern Europe: Gypsy marginality
      in the 1990s.

PMID- 19172780
TI  - Marriage, divorce, and legal change: new evidence from England and Wales.

PMID- 19172781
TI  - [Aragonese emigration to Argentina, 1880-1960].

PMID- 19172782
TI  - [Cuba: sugar production expansion and immigration: a regional approach].

PMID- 19172783
TI  - [Social networks and religious space: from a colony of Germans from Russia to an
      Adventist village. Puiggari, Argentina, 1870-1920].

PMID- 19172784
TI  - Local color. Children's hospital inspired by familiar scenes.

PMID- 19172785
TI  - Creating environment for cancer care.

PMID- 19172786
TI  - Wireless in the ED. Taking emergency departments to the next level.

PMID- 19172787
TI  - ICC update. International Code Council changes for 2009.

PMID- 19172788
TI  - 'Greening the cleaning. Implementing an environmentally friendly cleaning
      program.

PMID- 19172789
TI  - [Regulation of Wnt signaling pathway and its relationship with tumorigenesis].

PMID- 19172790
TI  - [Bioinformatics, systems biology and KEGG].

PMID- 19172791
TI  - [Molecular basis of hypophosphatasia].

PMID- 19172792
TI  - [Roles of chemokine signaling during development of the olfactory system].

PMID- 19172793
TI  - [Protein palmitoylating enzymes].

PMID- 19172794
TI  - [Regulation of store-operated calcium entry by STIM1].

PMID- 19172795
TI  - [Influenza virus replicon and host factors for its replication and
      transcription].

PMID- 19172796
TI  - [Novel roles of CXCL14 in obesity and glucose metabolism].

PMID- 19172797
TI  - [Dosage adjustments based on GFR--precautions for use of eGFR].

PMID- 19172798
TI  - [Nephritis and nephropathy].

PMID- 19172799
TI  - [Physiology and pathophysiology of tubular transport of solutes and water].

PMID- 19172800
TI  - [Comprehensive understanding of the fundamental theory on acid-base disorders].

PMID- 19172801
TI  - [Questions and comments concerning non-dialysis, dialysis and kidney
      transplantation].

PMID- 19172802
TI  - [Comparison between serum cystatin C and estimation of GFR by the MDRD study
      equation for chronic kidney disease].
AB  - Glomerular filtration rate(GFR) can be estimated from serum (s-) creatinine using
      the modification of diet in renal disease (MDRD). However, its calculation is
      sometimes cumbersome in clinical use. Cystatin C is less influenced by age,
      gender and muscle mass than serum creatinine, and it has been proposed as an
      alternative marker for estimating GFR (eGFR). The comparison of s-cystatin C with
      MDRD-eGFR from 245 Japanese outpatients with chronic kidney disease (CKD)resulted
      in the equation of eGFR = 82.8/s-cystatin C - 10.7 (r = 0.85, n = 245). Based on
      this equation, there were 22 patients above + SD, which was the high-group in
      which s-cystatin C levels were higher than the corresponding eGFR, and there were
      21 patients below -SD, which was the low-group in which s-cystatin C levels were
      lower than the corresponding eGER. Between the two groups there was no
      significant difference in age, gender, weight, and body mass index. The high
      group included 1 case of hyperthyroidism and 7 cases of steroid user. The low
      group included 4 cases of hypothyroidism and 1 case of steroid user. In healthy
      individuals, MDRD-eGFR is unsuitable for estimating GFR. Thyroid dysfunction or
      glucocorticoid excess are known to influence s-cystatin C levels. An improved
      eGFR equation was provided from 144 cases excluding 88 with normal renal function
      (eGFR > 90 mL/min/1.73 m2), 5 with thyroid dysfunction and 8 steroid users. eGFR
      = 86.1/s-cystatin C - 13.6 (r = 0.94, n = 144). Each GFR estimation provided from
      males or from females yielded nearly the same results as this equation. The
      prediction of eGFR using s-cystatin C may be convenient and useful in clinical
      practice, and the comparison of s-cystatin C with creatinine-based eGFR may
      reveal some factors that affect s-cystatin C or s-creatinine levels independent
      of GFR.

PMID- 19172803
TI  - [Clinical evaluation of tonsillectomy with modified high-dose intravenous
      methylprednisolone therapy in patients with IgA nephropathy].
AB  - Immunoglobulin A nephropathy (IgAN) is now recognized as the most common form of
      primary glomerulonephritis worldwide and is the major cause of end-stage renal
      disease. As reported, the renal survival rate is 61% at 20 years and the renal
      prognosis of this disease is relatively poor on long-term observation, hence
      various protocols have been attempted to control this disease. At Iizuka
      Hospital, a prospective study of tonsillectomy with methylprednisolone pulse
      therapy was performed for the treatment of patients with IgA nephropathy from
      August 2002. We reviewed the clinical efficacy of our protocol. From August 2002
      to July 2006, 31 patients whose IgA nephropathy was demonstrated by percutaneous
      renal biopsy were administered our regimen. In our study, 12 patients had an
      observation period of more than 24 months. Our protocol consisted of
      tonsillectomy with one course of methylprednisolone pulse therapy.
      Methylprednisolone at the daily dose of 1,000 mg for 3 consecutive days followed
      by oral steroid at the daily dose of 20 mg, was gradually tapered, and
      discontinued one year later. All of the patients were administered angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers with favorable
      control of hypertension. The mean observation period for the 12 patients with IgA
      nephropathy was 37.4 months. The mean age at renal biopsy was 34.8 +/- 12.2
      years. The male-female ratio was 3:9. At the renal biopsy in our hospital, mean
      creatinine value was 0.95 +/- 0.38 mg/dL, mean creatinine clearance was 92.1 +/-
      34.9 mL/min, and the mean urinary protein and urinary creatinine ratio was 3.52
      +/- 4.36. After 24 months, mean creatinine value was 1.03 +/- 0.59 mg/dL, mean
      creatinine clearance was 91.2 +/- 42.3 mL/min, and the mean urinary protein and
      urinary creatinine ratio was 0.83 +/- 0.98. Urinary protein and urine occult
      blood became negative in 66.7% of patients, and the urinary remission rate was
      58.3%. On our protocol, mean length of the hospital stay was 11.4 +/- 4.7 days.
      Our prospective study showed that tonsillectomy with one course of
      methylprednisolone pulse therapy in IgA nephropathy appears to be beneficial for
      urinary remission and contributes to a short hospital stay.

PMID- 19172804
TI  - [Case of Henoch-Schonlein purpura nephritis complicated with essential mixed
      cryoglobulinemia].
AB  - We report a case of purpura nephritis complicated with essential mixed
      cryoglobulinemia. The patient was referred to our hospital because of a petechial
      rash on the lower extremities, microscopic hematuria, and progressive
      deterioration of renal function. The presumptive diagnosis of Henoch-Schonlein
      purpura (HSP) was made, and the patient was treated with prednisolone at the dose
      of 40 mg/day. However, there was a persistent purpuric skin rash. On the other
      hand, immunoelectrophoresis of the serum revealed the presence of IgA-lambda and
      polyclonal IgG in the cryoprecipitate. Granular staining for polyclonal rather
      than monoclonal IgA and C3 segmentally along the capillary walls demonstrated by
      immunofluorescence analysis of renal biopsy led to the diagnosis of purpura
      nephritis as the major mechanism of renal damage. After three sessions of
      cryofiltration, the patient's serum cryoglobulins decreased and the active rash
      finally settled, along with improvement of renal function. These observations
      suggest that the presence of cryoglobulinemia modulated the clinical course of
      HSP in our case. Therefore, the possibility of the latent presence of
      cryoglobulinemia in cases with HSP having an active rash refractory to steroid
      treatment should not be overlooked.

PMID- 19172805
TI  - [Case of multiple nodular lesions of bilateral kidneys with IgG4-related systemic
      disease].
AB  - A 59-year-old woman was admitted to our hospital because of a pancreatic mass
      lesion. Serum gamma-globulin and IgG4 levels were elevated to 2.2 g/dL and 1,310
      mg/dL, respectively. Computed tomography examination revealed multiple low
      density areas without enhancement by contrast in the pancreatic body and
      bilateral kidneys. Endoscopic retrograde cholangiopancreatography images
      demonstrated diffuse narrowing of the main pancreatic duct with an irregular wall
      from the body to the tail of the pancreas. Positron emission tomography
      examination revealed intense 18F-fluorodeoxyglucose uptake by the pancreas and
      kidneys. Accordingly, the patient was diagnosed as having IgG4-related autoimmune
      pancreatitis. In addition, the findings of a renal tissue specimen obtained by
      biopsy demonstrated IgG4-positive plasma cell infiltration in both abnormal mass
      lesions and normal regions by imaging, leading to the final diagnosis of IgG4
      related sclerotic disease. The patient was treated with prednisolone (30 mg/day),
      and the size of the pancreatic and renal lesions markedly decreased four weeks
      later. We report here a rare case of IgG4-related autoimmune pancreatitis with
      multiple renal lesions, which were confirmed by renal biopsy.

PMID- 19172806
TI  - [Acute necrotizing tubulointerstitial nephritis due to adenoviral infection
      following hematopoietic stem cell transplantation: clinical findings obtained
      from 4 autopsy cases].
AB  - Once adenovirus infection extends to the kidney from the bladder in the
      immunosuppressive state after hematopoietic stem cell transplantation, most
      patients develop acute renal failure due to adenovirus-associated necrotizing
      tubulointerstitial nephritis. In the 6 years from 2000 to 2006, we
      retrospectively investigated the characteristics of adenovirus infection in 402
      patients who had received a hematopoietic stem cell transplantation in our
      hospital. The incidence of adenovirus-associated hemorrhagic cystitis in patients
      who had received a hematopoietic stem cell transplantation was 3.5% (14/402).
      Among these 14 patients, 4 developed acute necrotizing tubulointerstitial
      nephritis all of whom died, which yielded the incidence and mortality rates of
      the disease of 1.0% and 100%, respectively. Once adenovirus infection extends to
      major organs in a rapid manner, the patient's general condition becomes fatal.
      Further study is necessary to establish the diagnosis and treatment of adenoviral
      infections in a compromised host.

PMID- 19172807
TI  - [Has the number of children with developmental disorders really increased?
      Thinking about the role of this academic society while this anxiety exists].

PMID- 19172808
TI  - [3-year-old girl showing severe developmental regression in infancy].

PMID- 19172809
TI  - [Biopterin and child neurologic disease].
AB  - Tetrahydrobiopterin (BH4) deficiencies are disorders affecting phenylalanine
      metabolism in the liver and neurotransmitter biosynthesis in the brain. BH4 is
      the essential cofactor in the enzymatic hydroxylation of 3 aromatic amino acids
      (phenylalanine, tyrosine, and tryptophan). BH4 is synthesized from guanosine
      triphosphate (GTP), catalyzed by GTP cyclohydrolase I (GTPCH), 6-pyruvoyl
      tetrahydropterin synthase, and sepiapterin reductase (SR), and in aromatic amino
      acids, the hydoxylating system is regenerated by pterin-4a-carbinolamine
      dehydrolase and dihydropteridine reductase (DHPR). BH4 deficiency has been
      diagnosed in patients with hyperphenylalaninemia (HPA) by neonatal mass-screening
      based on BH4 oral-loading tests, analysis of urinary or serum pteridines, and
      measurement of DHPR activity in blood using a Guthrie card. BH4 deficiency
      without treatment causes combined symptoms of HPA and neurotransmitter (dopamine,
      norepinephrine, epinephrine, and serotonin) deficiency, such as red hair,
      psychomotor retardation, and progressive neurological deterioration. However,
      autosomal dominant GTPCH deficiency and autosomal recessive SR deficiency leads
      to BH4 and neurotransmitter deficiency without HPA and may not be detected by
      neonatal screening for phenylketonuria. The former is Segawa's disease, which is
      characterized by dopa-responsive dystonia with marked diurnal fluctuation and is
      caused by a defect of GTPCH, and the latter is SR deficiency, which is
      characterized by progressive psychomotor retardation, dystonia, and severe
      dopamine and serotonin deficiencies. Biochemical diagnosis is performed by the
      measurement of neopterin and biopterin levels, since both are low in Segawa
      disease, and the biopterin level is high in SR deficiency in cerebrospinal fluid.
      We must consider metabolic disorders of biopterin in child neurologic diseases
      with dystonia.

PMID- 19172810
TI  - [Retrospective analysis of pervasive developmental disorder patients initially
      diagnosed with attention deficit/hyperactivity disorder].
AB  - We retrospectively analyzed 66 patients with pervasive developmental disorder
      (PDD) whose respective diagnoses had been changed from attention
      deficit/hyperactivity disorder (AD/HD) and compared their clinical
      characteristics with those in patients whose diagnoses was not altered (n = 135).
      Of 52 patients, 41 (79%) had language delay or hyperactivity at initial
      examination. Of the 47 patients treated with methylphenidate, 41 patients (87%)
      responded favorably. The patients with altered diagnoses were categorized into
      three groups with inappropriate diagnoses (n = 32), amended diagnoses (n = 6),
      and dual diagnoses (n = 28). Consequently, some patients increasingly showed PDD
      characteristics concomitantly with age; other patients had justified dual
      diagnoses with PDD and AD/HD. The total points for peculiar behavioral history
      were significantly higher in patients with altered diagnoses than in those with
      unaltered diagnoses (5.4 +/- 3.7 vs. 2.6 +/- 2.6, p < 0.001). In particular, the
      points for language delay, indifference, and persistence were significantly more
      positive in patients with altered diagnoses. Results suggest that close
      evaluation of an individual's behavioral history might suggest a differential
      diagnosis between PDD and AD/HD.

PMID- 19172811
TI  - [Sulthiame treatment for patients with intractable epilepsy].
AB  - We examined the antiepileptic effect and side effects of sulthiame in 28 patients
      with intractable epilepsy. The patients' ages ranged from 6 months to 34 years
      (mean: 8 years 7 months), and 26 of them were under 18-years-old. Nineteen
      patients had severe physical and mental disabilities. Sixteen patients had
      generalized seizures, and 12 had partial seizures. Sulthiame was administered at
      the dose of 50-300 mg/day (4-14 mg/kg body weight) as add-on therapy in all
      except one patient. Among the 28 patients, two with complex partial seizures (7%)
      became seizure-free. Eight patients (29%) (6 patients with generalized seizures
      and 2 patients with partial seizures) showed seizure reduction by > 50%. Among
      these 10 patients who showed positive responses, six developed tolerance within 2
      5 months. Side-effects were observed in 5 patients, including enuresis,
      drowsiness, and drooling, none of which caused discontinuation of treatment.
      Therefore, we conclude that sulthiame is an effective and safe antiepileptic drug
      for the treatment of intractable epilepsy.

PMID- 19172812
TI  - [H reflex in patients with spastic quadriplegia].
AB  - Hoffmann reflex (H reflex) is an electrically elicited spinal monosynaptic
      reflex. H reflex was examined in 18 patients with spastic quadriplegia who had
      perinatal or postnatal problems. H reflex was elicitable in 11 patients for the
      abductor pollicis brevis (61.1%), 10 for the abductor digiti minimi (55.6%) and
      16 for the abductor hallucis (88.9%). Because the abductor pollicis brevis and
      the abductor digiti minimi do not exhibit H reflex in normal subjects, it was
      suggested that the excitability of alpha motor neurons innervating these muscles
      was increased. H reflex was not detected for the extensor digitorum brevis in any
      patients, indicating the difference in the excitability among alpha motor
      neurons. In some patients, H reflex did not disappear under supramaximal stimuli.
      We conclude that the mechanism of evolution of H reflex in patients with spastic
      quadriplegia is different from that in normal subjects.

PMID- 19172813
TI  - [Surgical management for intractable aspiration in handicapped children].
AB  - Intractable aspiration is a life-threatening medical problem. Sixteen patients
      with intractable aspiration underwent surgical management. Their underlying
      diseases were cerebral palsy (n = 6), degenerative diseases (n = 5), acquired
      hypoxic ischemic encephalopathy (n = 4), and congenital myopathy (n = 1).
      Laryngotracheal separation was performed in nine patients with median age of 2
      years 6 months (range: 7 mo - 13 y 5 mo), and laryngectomy was performed in seven
      with median age of 7 years 4 month (range: 1 y 6 mo - 17 y 1 mo). Surgical
      interventions were effective in all patients with respiratory distress. The most
      common complication was increased drawling in six patients, who recovered within
      6 months of clinical follow-up. Other complications were tracheal granulations (n
      = 4), bleeding (n = 2), narrowing of the tracheal hole (n = 2), tracheomalacia (n
      = 2), ruptured suture (n = 1), and tracheal abscess (n = 1). Considering the
      underlying diseases and age, surgical management for intractable aspiration
      should be performed at appropriate timing.

PMID- 19172814
TI  - [Acute encephalitis/encephalopathy associated with transient involuntary movement
      and limbic dysfunction in the recovery phase].
AB  - We report 3 patients aged 3 - 4 years who presented with impaired consciousness
      and status epilepticus or a cluster of seizures, followed by transient
      involuntary movements and limbic dysfunction in the recovery phase. In all the
      patients, the involuntary movements were observed mainly on the left side and
      consisted of dystonia, athetosis, chorea, facial myoclonus, and oral dyskinesia.
      The patients also showed stereotypic movement, oral tendency, visual agnosia, and
      emotional disturbance, which suggested limbic dysfunction resembling Kluver-Bucy
      syndrome. Single-photon emission computed tomography (SPECT) revealed
      hypoperfusion of the unilateral basal ganglia and the adjacent frontal and
      temporal lobes. No obvious lesions were observed on brain MRI in the acute phase
      in 2 patients, who recovered completely during the follow-up period. However, the
      last patient, who had abnormalities with regard to the limbic system and
      subcortical white matter on diffusion-weighted image in the acute phase,
      exhibited mental retardation, epilepsy, and persistent oral tendency during the
      follow-up period.

PMID- 19172815
TI  - [Treatment approach to congenital myasthenic syndrome in a patient with
      acetylcholine receptor deficiency].
AB  - Congenital myasthenic syndromes (CMS) are rare heterogeneous disorders of
      neurotransmission caused by genetic defects of neuromuscular junction molecules.
      While CMS patients have been reported worldwide, in Japan there have been only a
      few descriptions of adult CMS patients with acetylcholinesterase (AChE)
      deficiency and slow channel syndrome. Herein, we report a Japanese CMS patient
      with acetylcholine receptor (AChR) deficiency, diagnosed during childhood, and
      our treatment approach to the patient. This 13-year-old Japanese boy had had
      severe myasthenic symptoms since infancy. Ptosis, his first symptom, appeared at
      5 months and nasal voice was recognized at 2 years of age. AchR and anti-muscle
      specific tyrosine kinase (Musk) antibody remained negative. A positive tensilon
      test and decremental response on electromyogram supported the diagnosis of sero
      negative myasthenia gravis. Despite thymectomy and strong immunosuppressive
      therapy including steroid pulse and FK 506, he gradually deteriorated and became
      wheelchair bound. Genetic analyses for AchR, Rapsyn, Musk and AChE were negative.
      At age 11 years, a muscle biopsy was performed in the deltoid muscle for
      neuromuscular junction sampling. Electron microscopic and confocal microscopic
      analysis of endplates showed almost complete loss of AChR and the diagnosis of
      CMS with AChR deficiency was confirmed. All immunosuppressive therapies were
      discontinued. Instead, we started Ubretide and 3,4-diaminopyridine (DAP) after
      obtaining informed consent. Although not approved in Japan for this use, 3,4-DAP
      is reportedly effective in refractory cases of CMS. The patient experienced no
      side effects. Despite all of the objective data were improving, his subjective
      symptoms and ADL remained poor. There are still many challenges in the treatment
      of the patient.

PMID- 19172816
TI  - [Case of infantile autism with pediatric Wernicke's encephalopathy due to severe
      eating disorder].
AB  - Wernicke's encephalopathy (WE) or thiamine deficiency is fatal if left untreated.
      We report a case of a 3-year-old boy with infantile autism and a severe eating
      disorder who developed WE after 3 weeks of starvation without thiamine
      supplementation. The eating disorder started when he entered preschool. He
      presented with unconsciousness and a cluster of seizures. Cranial magnetic
      resonance imaging (MRI) showed high-intensity signal changes in the basal ganglia
      on T2-weighted images and fluid-attenuated inversion recovery (FLAIR). Treatment
      with high-dose intravenous thiamine was effective. Pediatric patients with WE
      tends to show no typical symptoms or brain lesions on MRI as seen in adult WE
      patients typically along alcoholics. Brain lesions similar to those in hypoxia or
      mitochondrial diseases such as Leigh's encephalopathy, are observed in patients
      with pediatric WE, and this makes diagnosis difficult. WE should be considered
      when patients with severe eating disorders present with unconsciousness and/or
      frequent seizures, and show basal ganglia lesions on MRI, differential diagnosis
      should include WE.

PMID- 19172817
TI  - [Recurrent idiopathic cerebral infarction in a 5-year-old boy, with emphasis on
      the importance of platelet aggregation analysis for appropriate selection of anti
      platelet drugs].
AB  - We present a 5-year-old boy with recurrent idiopathic cerebral infarction in
      which analysis of platelet hyperaggregability was useful in choosing appropriate
      anti-platelet drugs. The patient presented with gait disturbance at the age of 5
      years and 1 month. Brain MRI demonstrated multiple infarctions in the right
      thalamus and left cerebellum. There were no apparent underlying diseases
      including hematological, cardiac and vascular abnormalities. He was diagnosed as
      idiopathic cerebral infarction. First, we administered ticlopidine and he
      remained stable with persistent mild intention tremor in the left upper extremity
      for 4 months. Then he developed the second stroke at the age of 5 years and 5
      months, and multiple infarctions in the right celebellum and cerebellar vermis
      were demonstrated. On platelet aggregation analysis, adenosine diphosphate (ADP)
      induced aggregation was inhibited, probably due to ticlopidine administration.
      Collagen- and epinephrine-induced platelet aggregation showed hyperaggregation,
      so we started to administer cilostazol, which inhibits only epinephrine-induced
      hyperaggregation. We also added aspirin, which inhibits collagen-induced
      hyperaggregation. The combination of anti-platelet drugs inhibited epinephrine-,
      collagen- and ADP-induced hyperaggregation in this patient. He has been stable on
      the triple combination of anti-platelet drugs without further episodes of
      cerebral infarction or transient ischemic attack for 4 years to date. Appropriate
      selection of anti-platelet therapy was achieved by the simple and repeatable
      platelet aggregation analyses, which must be considered even in pediatric
      patients with cerebral infarction.

PMID- 19172818
TI  - [Case of Sturge-Weber syndrome manifesting complex partial status epilepticus].
AB  - A three-year-old boy presented with status epilepticus with right hemiconvulsion
      and complex partial status epilepticus (CPSE) that were preceded by disturbance
      of consciousness and right hemiplegia just after a traumatic head injury. He was
      diagnosed as Sturge-Weber syndrome (SWS) because of the presence of a small
      cutaneous port-wine nevus and the nature of his MRI findings. The nevus was
      located in the middle of the forehead and was light in color. Intravenous drip
      infusion of lidocaine was effective for the treatment of CPSE, but the patient
      has experienced refractory complex partial seizures since then. It has not yet
      been reported that patients with SWS developed CPSE following head trauma,
      although it is known that patients with SWS can manifest convulsive status
      epilepticus. CPSE should be recognized as one of the seizure types of SWS.

PMID- 19172819
TI  - [Reliability of rapid word reading test in children with developmental
      disorders].

PMID- 19172820
TI  - [Flash visual evoked potential findings in unilateral schizencephaly].

PMID- 19172821
TI  - Analysis of factors of treatment completion in dots health facilities in metro
      Manila, Philippines: a case-control study.
AB  - STUDY BACKGROUND AND OBJECTIVES: The Philippines is one of the 22 countries with
      high TB burden. DOTS was adopted not only by purely public providers (PP) but
      also by public-private mix (PPM) facilities. This study aims to identify the
      patient and facility factors that promote completion of TB treatment in DOTS
      facilities in an urban setting. The study also explores the difference between
      the PP and PPM DOTS facilities in terms of case management and treatment
      outcomes. [Methods] A case control study was done by interviewing 394 patients
      sampled from TB cohort report between 2003 and 2005 of 14 DOTS facilities in
      Metro Manila. Statistical analyses used include chi-square test and logistic
      regression analysis. RESULTS: Being female and aged 30-44 (OR = 7.04; 95% CI 1.12
      44.35), unemployed (OR = 2.73; 95% CI 1.18-6.33), being above per capita poverty
      threshold (OR = 2.03; 95% CI 1.03-3.99), having experienced at least one of the
      signs and symptoms of TB (OR = 4.64; 95% CI 1.29-16.67), taking the medication at
      health facility (OR = 3.87; 95% CI 1.48-10.16) and patient's understanding of DOT
      (OR = 2.67; 95% CI 1.37-5.23) predict TB treatment completion. Public-private mix
      type of DOTS facility was also significantly associated with completing treatment
      (chi 2 (1) = 54.76, p = 0.000). CONCLUSION: Patient factors like middle-aged
      female compared to female aged more than 60, being above per capita poverty
      threshold, unemployment and having experienced at least one signs and symptoms of
      TB and facility factors like providing treatment at the facility and explaining
      the DOT to patient increase the likelihood of completing treatment. Thus,
      encouraging patients to take their medication at the facility and helping the
      patients understand the importance of DOT can increase TB treatment completion.
      The seemingly better DOTS implementation and treatment outcomes by the PPM must
      be evaluated further through cost effectiveness and efficiency studies.

PMID- 19172822
TI  - [Clinical research on multi-drug resistant and extensive drug-resistant
      tuberculosis in Japan].
AB  - PURPOSE: To know the number of patients with MDR-TB and XDR-TB newly diagnosed
      annually and the number of those with continuously culture-positive in spite of
      continued treatment. METHODS: To fill the questionnaire sent to all the TB
      hospitals in Japan and to investigate the number of beds for TB, MDR-TB cases
      newly admitted to each hospital in 2006 and chronic bacillary cases in spite of
      continued treatment. RESULT: We sent the questionnaires to all the TB hospitals
      in Japan and 81% of 270 hospitals replied. As the result, 93 MDR-TB were newly
      hospitalized (12 cases were with XDR-TB). 76 cases of them were newly diagnosed
      MDR-TB. Almost after 1 year treatment, patients with XDR-TB showed lower negative
      conversion rate than other MDR-TB (42.9% vs 63.8%) and higher fatality rate
      (42.9% vs 7.2%). Excluding above 93 new MDR-TB cases, 103 cases with chronic MDR
      TB including 44 cases with XDR-TB had been treated during the observation period,
      84 case had been hospitalized and other 19 cases at OPD. DISCUSSION: Since 2000,
      extensive multi-resistant (XDR) TB has been a global topic. In Japan, nation-wide
      survey on 2002 showed the ratio of MDR and XDR were 1.9% and 0.6% respectively
      out of 3122 TB stains investigated. XDR/MDR rate was higher than those in other
      countries. Our clinical based investigation showed total XDR/MDR rate was 28.6%
      (56/196) and it was similar to that of previous bacteriological survey in 2002.
      CONCLUSION: We investigated the number of patients with MDR-TB and XDR-TB newly
      diagnosed in 2006 and the number of those who were continuously culture-positive.
      The survey showed that there were 196 patients with MDR-TB, and 56 patients of
      them (28.6%) were with XDR-TB. Many of them were in the districts of Kinki area
      and Kanto-Shinetsu area and 70% of them had been treated in the hospitals
      belonging to the National Hospital Organization.

PMID- 19172823
TI  - [Long-term observation of pulmonary Mycobacterium avium complex disease treated
      with chemotherapy-- following the guidelines for treatment].
AB  - OBJECTIVE: We performed a long-term retrospective investigation of pulmonary
      Mycobacterium avium complex (MAC) disease treated with combined chemotherapy
      following the ATS guideline or the Japanese Society for Tuberculosis guideline.
      We also studied when to terminate the combined chemotherapy. MATERIALS AND
      METHODS: The subjects of this study consisted of 90 patients who underwent
      combined chemotherapy according to these guidelines for minimum one-year period
      and followed up for at least one year since April, 1998. RESULTS: The mean
      patients' age was 64.8 years old and the gender distribution consisted of 34
      males and 56 females. While the sputum negative conversion was observed in 54 of
      90 patients (60%), clinical improvement was recognized in 35 patients (39%)
      following combined chemotherapy administered according to the guidelines. Out of
      54 patients with sputum conversion, 30 cases were followed up after the
      discontinuation of treatment, and sputum relapse later was seen in 18 patients.
      Out of 24 patients who continued the same treatment, sputum relapse was seen in
      10 patients. Out of 35 patients with clinical improvement, 17 cases have been
      followed up after the discontinuation of treatment, clinical worsening was later
      recognized in 9 patients. Out of 18 patients who continued the same treatment,
      clinical worsening was recognized in 6 patients. CONCLUSIONS: As the probability
      of sputum relapse after discontinuation of treatment was high even among patients
      whose sputum converted to negative by combined treatment according to the
      guidelines, we think that it is better to continue treatment according to the
      guidelines as long as possible.

PMID- 19172824
TI  - [Usefulness of bronchofiberscopy for the diagnosis of pulmonary non-tuberculous
      mycobacteriosis--an analysis mainly on pulmonary M. avium complex disease].
AB  - OBJECTIVES: The aim of this study was to evaluate the usefulness of
      bronchofiberscopy (BFS) in the diagnosis of pulmonary non-tuberculous
      mycobacteriosis (PNTM). MATERIALS AND METHODS: Among 909 PNTM patients admitted
      to our hospital during the period from 1995 to 2006, BFS was performed for the
      diagnosis of PNTM in 107 patients (12%) who had either a negative sputum-smear
      for acid-fast bacilli (AFB) (n = 100) or from whom it had been impossible to
      collect sputum (n =7). For these 107 cases, we retrospectively compared and
      analyzed the findings from specimens obtained by BFS, such as smears, cultures,
      polymerase-chain reaction (PCR), and transbronchial lung biopsy (TBLB), with
      clinical, radiological, and sputum examination disease, was also seen in the
      positive ratios of other nontuberculous mycobacteriosis cases. Type and/or spread
      of MAC disease on chest radiographs did not relate to positive ratios of BFS
      obtained specimens. Based on overall BFS findings, including the examination of
      sputum immediately after BFS, 68 of 92 (74%) patients met the diagnostic criteria
      of MAC disease. Furthermore, through a combination of positive-TBLB findings and
      positive-PCR findings of BFS specimens, we were able to obtain an early and
      strong indication of MAC disease in 17 of 36 (47%) patients. CONCLUSION: Using
      BFS to obtain various kinds of specimens is a useful tool for the early and
      definite diagnosis of PNTM/pulmonary MAC disease.

PMID- 19172825
TI  - [Start of PTB (Phthisis) mortality statistics in Japan (1)].
AB  - First "Statistics Annual", which included the population and vital statistics was
      published in Japan in 1882, and the numbers of death classified by major causes
      of death were tabulated by sex and age groups and by prefecture. Koch R reported
      the discovery of tubercle bacilli as the pathogen for TB in 1882, and since the
      latter half of 1883, the numbers of death due to PTB (Phthisis) were tabulated by
      prefecture, and by sex and age groups since 1884 annually except for 1885. Based
      on the population statistics and the numbers of PTB death, PTB (Phthisis)
      mortality was calculated by sex and age groups, and the results were shown in
      Table 1. PTB mortality per 100,000 increased from 78.2 in 1884 to 171.9 in 1899.
      Sex- and age-specific PTB mortality in 1884 showed a pattern increasing with age,
      and the PTB mortality of male was higher than that of female in adult as shown in
      Fig. 2. In 1889, low peak of mortality was seen in the age groups 15-19 and 20
      29, and in these age groups, the PTB mortality was higher in female than in male.
      Such trend was seen more markedly in 1894 and 1899, while the rate was higher in
      male than in female in the age groups over 40. Trend of PTB mortality by sex and
      age groups was shown in Fig. 3. Rapid increase of PTB mortality in the age groups
      10-14 and 20-29 could be explained by the rapid increase of young women workers
      in fast growing silk and spinning industries, but how rapid increase of PTB
      mortality in infants be explained? In "Statistics Annual", PTB (Phthisis)
      mortality rate by prefecture was printed, and the summarized table was shown in
      Table 2. The rates in 1883 and 1884 were calculated from the numbers of PTB death
      and the B-type population shown in the "Statistics Annual", which will be
      described in the next issue of this paper.

PMID- 19172826
TI  - [Some topics of TB research using epidemetric models].
AB  - Recent challenges to research in tuberculosis (TB) epidemiology were overviewed,
      with special emphasis on studies using mathematical models. They include; the
      effectiveness of DOTS strategy on TB epidemiology, impact of HIV epidemics and
      multi-drug resistant TB, simulation of selected TB control measures (BCG
      vaccination, case-finding, the use of interferon-gamma release assay for sub
      clinical infections). The perspectives on molecular epidemiology and the host
      susceptibility are discussed, and these topics are considered as important
      research agendas in TB epidemiology. Also, discussions were made on the relevant
      ways of organizing epidemiological studies in TB, now and in the near future.

PMID- 19172827
TI  - [Evaluation of the tuberculosis control program through tuberculosis
      surveillance].
AB  - Tuberculosis (TB) surveillance has involved three main functions: (1) data
      collection, (2) data analysis, and (3) feedback. There is now one more important
      function: (4) a new action plan based on the results of feedback. If all four
      functions are operating smoothly, the result will be effective so-called "program
      surveillance". In Japan, the first nationwide computerized TB surveillance system
      was established in 1987 and it was revised in 1992, 1998 and 2007. Treatment
      outcomes have been decided automatically in this system since 1998, based on data
      concerning treatment status, bacteriological test results and so on. Two optional
      systems, the recording of DOTS and managing of contact tracing, were added to
      this system in 2007. Since we can thus obtain and use a large amount of
      surveillance data, we have developed assessment indicators and methods of
      evaluating the national or regional TB control programs (Fig. 1). However, the
      accuracy of surveillance data entered into computers at public health centers has
      been inadequate. Therefore, one of the objectives of evaluating regional TB
      control program activities is to improve the quality of surveillance data. As
      regional governments have responsibility for TB control programs in Japan, TB
      control is generally evaluated at the regional level; i.e. prefecture and
      designated city. This evaluation process should be done in the cycle of "Plan-Do
      See" (planning, execution, evaluation). However, the priority of "See" in this
      cycle seems to be low, because of the heavy workload of TB control activities.
      Nevertheless, the evaluation of TB control is very important, so I have
      introduced some examples of evaluation methods in WHO and Osaka city, and propose
      the optimum approach to evaluating TB control programs at the regional level.
      This approach is: (1) to observe the correct epidemiological situation, (2) to
      set a clear goal, (3) to announce the strategy, and (4) to carry out an annual
      evaluation. It might also be possible to evaluate the national TB control program
      by the same process. However, unfortunately there is no national organization
      such as a TB surveillance committee. I therefore propose setting up a TB
      surveillance committee in Japan as soon as possible. Since the number of TB
      specialists has been decreasing in Japan, advice and support for regional TB
      control will become increasingly important. An organization such as a TB
      surveillance committee would serve as supervisor.

PMID- 19172828
TI  - [Anorectal Lesniowski-Crohn's disease].
AB  - Authors retrospectively reviewed results of surgical treatment of the patients
      with anorectal Lesniowski-Crohn's (LC) disease, operated in the Department of
      General and Gastroenterological Surgery in Warsaw. MATERIAL AND METHODS: In years
      1987-2007 we treated 110 patients with LC disease. The anorectal localization of
      lesions was noticed in 24 patients (13 women, 11 men, average age of fall--28
      year), i.e. 21.8% of all patients. The operations performed in other hospitals
      were taken into account. Results were compared with literature data. RESULTS:
      Anorectal lesions were the first signs of LC disease in 16/110 patients (14.5%),
      and there were most often: perianal fistulas (multiple) in 12, perianal abscesses
      in 2, and rectovaginal fistula in 2 patients. In the remaining 8 patients (7.3%),
      anorectal lesions emerged in later period of the disease, formerly placed in
      other part of digestive tract. The primary local surgical treatment
      (incision/excision offistulas, abscess drainage) was performed in 20/24 patients.
      Most frequent indications were: perianal fistulas--13, perianal abscesses--6, and
      rectovaginal fistula--1. Primary abdominal operations were performed in 4/24
      patients: Hartman procedure in 2 patients with rectovaginal fistulas and in other
      2 patients with severe colitis--subtotal colectomy and restorative
      proctocolectomy. The follow-up in 23/24 patients exceeded 5 years, only in 1
      patient was 4 years. The surgical recurrences were noticed in 19/24 (79.1%)
      patients. Recurrences of fistulas were noticed in 11 patients, in addiction in 5
      patients we noticed anal stenosis, in 3 rectal/sigmoidal stenosis and in 3
      proctitis of the remaining rectal stump. Surgical recurrences of LC disease after
      5, 10 and 15 years of observation were 18/23--78.2%, 14/15-93.3%, and 7/7--100%
      respectively. Two patients (8.3%) died from severe general complications of the
      disease. The primary local surgical treatment was sufficient only in 2 patients.
      In 18/22 patients 28 abdominal operations were carried out in later period of the
      disease. In all 24 patients we performed 46 extended abdominal operations. In
      result of them 13/24 patients have definitive and 1 temporary stoma. CONCLUSIONS:
      1. Surgical treatment of anorectal LC disease should be sparing and performed in
      the proper time. 2. Surgical treatment of anorectal LC disease is difficult and
      should be carried out in reference centers. 3. Anorectal LC disease has poor
      prognosis in terms of fecal and gas continence and creates the risk of
      proctectomy in up to 20% of cases.

PMID- 19172829
TI  - [Back pain in children].
AB  - Back pain and pain of the surrounding structures leads to significant diagnostic
      and therapeutic difficulties which result from a complex pathomechanism. They are
      the symptom of a large number of pathologic processes that may to a varying
      extent contribute to pain related manifestation of symptoms. In 80-90% of cases
      the cause of the back pain remains unknown, only in 10-20% adult patients it is
      feasible to establish the etiological factor during one year observation.
      Contrary to the situation in adults, in over 50% of children it is possible to
      identify the cause of the reported ailments. The authors present etiological
      factors and clinical symptoms in 44 patients, hospitalized because of back pain
      in Child Neurology Department of Medical University of Silesia in Katowice in the
      period between 2004 and 2007.

PMID- 19172830
TI  - [Role of c-c chemokines in the determination of pleural effusion etiology].
AB  - The purpose of the study was to evaluate predictive value of vascular endothelial
      growth factor (VEGF) in the differential diagnosis of pleural effusion. MATERIAL
      AND METHODS: By Light's criteria in 29 cases exudates and 10 transudates was
      recognized. We investigated 39 patients with pleural effusion (congestive heart
      failure--10, parapneumonic--11, tuberculous--6, malignant--12, transudate--10).
      RESULTS: The mean VEGF value were significantly higher (p = 0.002) in the
      effusion of lung cancer patient (3958.33 pg/ml) than in the serum (1030.33
      pg/ml). The mean VEGF levels were significantly higher (p = 0.004) in patient
      with exudates (2711.10 pg/ml) than in transudates (683 pg/ml). Based on the
      receiver operating characteristic (ROC) curve analysis, cut off value in
      differentiation of exudates and transudates was accepted at the level of 560
      pg/ml (sensitivity 80% and specificity 70%). The mean VEGF levels were
      significantly higher (p = 0.008) in the malignant effusion (3958.33 pg/ml) than
      in the tuberculous effusion (1308.90 pg/ml). Based on the ROC curve analysis, cut
      off value in differentiation of malignant and tuberculous effusion was accepted
      at the level of 2000 pg/ml (sensitivity 92% and specificity 83%). The positive
      correlation between pleural VEGF concentrations and pleural lactate dehydrogenase
      (LDH) level were observed (r = 0.67, p < 0.05). CONCLUSION: We conclude that
      pleural effusion VEGF level could be useful in the differentiation between
      exudates and transudate and also between malignant and tuberculous exudates.

PMID- 19172831
TI  - [Analysis of treatment results of boys referred to outpatient paediatric surgery
      centre with recognition of phimosis].
AB  - The problem with prepuce retraction is caused not only by its narrowing, called
      phimosis, but also frequently by the inner prepuce adhesion to glans. The
      spontaneous prepuce retraction is received in 80% cases of boys up to the age of
      two, whereas in remaining cases, after the age of two it is necessary to take up
      the medical treatment. The purpose of the research was to estimate the
      effectiveness of conservative therapy using steroid ointments which was
      undertaken in boys referred to Outpatient Paediatric Surgery Centre with
      recognition of phimosis. MATERIAL AND METHODS: Cases of 315 boys referred to
      Outpatient Paediatric Surgery Centre due to phimosis were analyzed between April
      2004 and May 2007. At the first appointment the boys were divided into 3 main
      groups: I--children with foreskin adhesion without visible stenosis (near 20%),
      who had the prepuce adhesion released in a local anaesthetic with Emla cream; II-
      children with narrowed foreskin (phimosis) who were treated with the use of
      conservative therapy by means of topical steroids (about 70%); III--children with
      stenosed prepuce (phimosis) developed to a large extent, who were immediately
      qualified to a surgery therapy without trying the conservative therapy (near
      10%). RESULTS: Among all patients about 1/5 needed the prepuce adhesion releasing
      with the use of Emla ointment only. High efficiency of conservative treatment
      with topical steroids was revealed both in primary and acquired phimosis.
      Reduction of the therapy time of children treated with topical steroids because
      of primary phimosis in relation to those treated surgically was taken into
      account. CONCLUSION: Conservative treatment of phimosis is highly effective and
      safe method which may also be an initial stage to operative treatment or to cure
      scarring after surgical treatment as well.

PMID- 19172832
TI  - [Pouchitis--what do we know after 30 years?].
AB  - The restorative proctocolectomy is a surgical procedure performed from 30 years
      in patients with ulcerative colitis and familial adenomatous polyposis. The ileal
      pouch anastomosed with anal spincters replaces the function of the excised colon
      and enables the natural rout of intestinal contents. The most frequent
      postoperative complication is pouchitis, often lowering the estimation of the
      operation. Authors described the current opinions in ethiopathogenesis and
      treatment of this disease.

PMID- 19172833
TI  - [Methods of taste sensitivity examination].
AB  - Taste is the main sensory system that keeps a check on ingested food. Human
      beings are able to recognize five basic tastes: salty, sour, sweet, bitter and
      umami. Gustometry, including both gustometry with application of taste substances
      and electrogustometry, is the method of taste examination. There are various
      methods of applying taste substances during gustometry examination. The stimuli
      used in gustometry are: citric acid or hydrochloric acid (sour taste), caffeine
      or quinine hydrochloride (bitter taste), sodium chloride (salty taste),
      saccharose (sweet taste), monosodium glutamate (umami taste). Electrogustometry,
      widely used by clinicians to examine taste sensitivity, allows to estimate the
      functioning of taste by means of electric excitability thresholds determined
      through the response to the irritation of taste buds area with electrical current
      of different intensity. Electrogustometry is especially useful in estimating the
      efficiency of sensory pathways. However, if we want to examine taste sensitivity
      to individual taste categories we should use more laborious gustometry with the
      application of taste substances, which main advantage is the use of physiological
      stimuli.

PMID- 19172834
TI  - [Analysis and importance of statistical power and sample size in empirical
      scientific research].
AB  - In order to define completely the mining of significant test it is essential to
      have the knowledge of test's statistical power. We intuit that when two tests are
      performed it is the one with a bigger power that is preferable. It means that
      when two tests have the same sample size and the same significance level a,
      better is the one which rejects the false null hypothesis more often. When
      planning the empirical scientific research it is cardinal to know how big the
      effect must be and what level of power of statistical test has to be achieved to
      be satisfied with the overall outcome. Four versions of power analysis are being
      presented. They are accessible in Power Analysis procedure of STATISTICA
      software. The analysis of statistical power supports one of the most severe
      problems in clinical research such as exposing objects of the study to the risk
      of injury, unpleasantness and inconvenience during the experiment. It happens
      that when scientist try to draw a particular clinical conclusion too little data
      are taken into account and the risk of receiving false negative results is
      getting higher. The opposite situation appears when in order to justify the
      outcome of the experiment too many data are taken which leads to false positive
      results.

PMID- 19172835
TI  - [Situation-related seizures in patients at developmental age].
AB  - The seizures which accompany specified situations occur in about 5% of
      population. They are frequent in patients at developmental age due to a different
      degree of brain maturity. A single, occasional seizure event which occurs in
      specified situations is not an epilepsy but it constitutes a significant clinical
      problem which requires a thorough diagnostics and procedure. We discuss situation
      related seizures (also called acute symptomatic seizures) in children, excluding
      febrile convulsions. We bring attention to situation-related seizures
      characteristic only of developmental age.

PMID- 19172836
TI  - [Patient with dyspnoea and gigantic tumor of the chest].
AB  - We describe the patient with gigantic chest tumor admitted to the hospital
      because of dyspnoea. The patient was operated on after the elimination of
      suspicion of acute pulmonary embolism. Cardiovascular failure was caused by the
      huge arterial-venous fistula in the tumor and diastolic heart failure were the
      reasons for dyspnoea. On the basis of the microscopic examination
      hemangiopericytoma (HPC) was diagnosed--a mesenchymal tumor derived from
      pericytes. We present in our paper the rules applying to dealing with HPC.

PMID- 19172837
TI  - [Non-epithelial tumors of the large intestine].
AB  - Colorectal cancer may arise from any kind of tissue constituting normal wall of
      the large intestine, however, in majority of cases, it is of epithelial origin.
      Endocrine, mesenchymal neoplasms and non-granulomatic lymphomas belong to rarely
      occurring cancers of the large intestine. Mesenchymal neoplasms may derive from
      muscles, nervous system, fibrous connective tissue, fat tissue and from blood and
      lymphatic vessels. The paper presents 3 cases of non-epithelial neoplasms of the
      large intestine (myosarcoma and 2 myomas). All cancers concerned women older than
      50 years (mean age 64.6 +/- 11.4 years) and were localized in the right
      hemicolon. In all cases episodes of hemorrhage from the lower part of the
      digestive tract triggered the diagnostic procedures. Surgical treatment varied
      from hemicolectomy with lymphadenectomy to endoscopic excision of a small lipoma.
      Histopathological verification and immunohistochemical staining were obtained
      after their removal. Clinical course and intraoperative situation were decisive
      as to type of surgery. Although mesenchymal tumors are very rare among large
      intestine neoplasms, one should consider their occurrence while carrying
      preoperative diagnosis. CONCLUSION: Occurrence of other tumors than neoplasms
      should be taken into consideration while carrying preoperative diagnosis.

PMID- 19172838
TI  - [Dermatofibrosarcoma protuberans of the vulva].
AB  - Dermatofibrosarcoma protuberans (DFSP) is a locally malignant neoplasm derived
      from fibrous tissue. Similar picture of such lesions to malignant tumors as well
      as to benign changes creates a risk of too gentle treatment and consequently of
      recurrence and malignant transformation of the lesions with possible remote
      metastases. Therefore accurate diagnosis and aggressive surgical treatment can
      prevent the recurrence of the tumor. Authors of the study present case report of
      49-year-old woman with DFSP of vulvar area.

PMID- 19172839
TI  - [A rare case of neurilemmoma of the floor of the mouth].
AB  - Neurilemmoma is a benign neoplasm of neuroectodermal origin. The authors present
      a rare case of this lesion localized in the oral cavity. Clinical symptoms,
      histologic structure of the tumor, methods of treatment and differential
      diagnosis are described.

PMID- 19172840
TI  - [Memory hallucinations as an untypical symptom in schizoaffective disorders-
      legal doubts].
AB  - The authors have described diagnostic difficulties of patient with memory
      hallucinations. A 45-year-old man, previously hospitalized many times on the
      Psychiatry Department was admitted to the Psychiatry Department after another
      suicidal attempt. During the examination the patient has confessed that he had
      committed a crime. This cause that doctor was on the horns of a dilemma of
      writing his statement in case history. Psychiatric and psychological diagnostics
      have showed memory hallucinations. Paying attention to legal aspect allowed to
      solve the problem. The frequency of occurrence of memory hallucinations still has
      been the question today.

PMID- 19172841
TI  - [Complications after alcoholization of mental nerve].
AB  - Trigeminal neuralgia (TN) is a syndrome affecting usually one half of the face
      and consisting of severe pains within one or more branches of the nerve. One of
      the methods for conservative treatment is using anesthetic drugs in the form of
      perineural sensory branch blockades n. V. If these are found ineffective,
      alcoholic blockades are used in some cases although complications like necrosis,
      tissue fibrosis or risk of developing a neuroma may occur. The paper describes a
      case of complication after alcoholic blockade into left mental nerve, namely oral
      tissue necrosis.

PMID- 19172842
TI  - Integrative genomics--a basic and essential tool for the development of molecular
      medicine.
AB  - Understanding the molecular mechanisms of disease requires the introduction of
      molecular diagnostics into medical practice. Current medicine employs only
      elements of molecular diagnostics, and usually on the scale of single genes.
      Medicine in the post-genomic era will utilize thousands of molecular markers
      associated with disease that are provided by high-throughput sequencing and
      functional genomic, proteomic and metabolomic studies. Such a spectrum of
      techniques will link clinical medicine based on molecularly oriented diagnostics
      with the prediction and prevention of disease. To achieve this task, large-scale
      and genome-wide biological and medical data must be combined with biostatistical
      analyses and bioinformatic modeling of biological systems. The collecting,
      cataloging and comparison of data from molecular studies and the subsequent
      development of conclusions create the fundamentals of systems biology. This
      highly complex analytical process reflects a new scientific paradigm called
      integrative genomics.

PMID- 19172843
TI  - Harnessing stem cells and dendritic cells for novel therapies.
AB  - This review presents the latest achievements in basic studies on stem-cell
      biology and on approaches aimed to design therapies based on stem cells and
      dendritic cells. Studies on stem-cell homeostasis are aimed to delineate the
      accessibility of these cells for therapeutic purposes. Hematopoietic stem cell
      transplantation has become a routine application of stem cells in the treatment
      of patients with cancer and with hematologic disorders. Perspectives of
      application of the mesenchymal stem cells for regenerative medicine and for
      tolerance induction following allogeneic transplantation are being extensively
      explored. Reprogramming of adult somatic cells to an undifferentiated pluripotent
      state in vitro by a transduction with just four genes encoding transcription
      factors opened the way for the generation of patient-specific pluripotent stem
      cells. Such induced pluripotent stem cells hold a great promise for replacement
      therapies of various so far incurable disorders. However, because of the
      tumorigenic potential of the retroviral vector transduction-induced pluripotent
      stem cells, before these cells become useful for clinical application,
      appropriate, safe methods of stem cell generation, selection, proliferation and
      differentiation need to be elaborated. There is a great potential for further
      developments of cancer immunotherapies and for controlling of post
      transplantational reactions, if current basic studies on stem cells and on
      immunostimulatory and tolerogenic dendritic cells would be successfully
      translated to the clinic.

PMID- 19172844
TI  - Molecular underpinnings of the targeted therapy for cancer.
AB  - Cancer is a real challenge for modern medicine. Biologically, it is of a host
      origin and therefore its eradication appears not so easy as one could expect to
      do it. Cancer presents itself with many faces as if it would be Janus the deity.
      The basic knowledge on tumorigenesis at the level of evolutionary science is
      weak. Additionally, accumulating molecular data are still focused on experimental
      systems, but more important fact is to determine the molecular pathobiology that
      could have impact on improvement of control of malignant disease. Poland is among
      the countries with high cancer morbidity and mortality. Multidisciplinary
      approach to detect, control, and treat cancer diseases is the only way to get
      improved clinical results. Moreover, it is worth pointing out that individual
      considerations of every patient would offer clinical benefits. Biology of human
      tumors with the modem armament of molecular and chemical methods would be a help
      hand to construct novel drugs. Making a list of crucial pathways worth blocking
      with their translation into clinical benefits appears to be a great step forward.
      Chemistry is a real partner to modem medicine due to a technical possibility to
      have impact on molecules (xenobiotics) that will finally become approved drugs.
      Combinatorial chemistry offers automated methods for pipeline organic synthesis a
      large number of chemicals that are further capable of undertaking investigation
      at a bed. Many chemicals have been used for more than ten years upon treating
      various cancer patients. New drugs have various origin , i.e., monoclonal
      antibodies (Herceptin, Erbitux, Avastin) or small molecules (Glivec, Tarceva,
      Sutent, Nexavar). We do hope that in the future many new drugs will be available
      for treatment of particular disease in relation to genetic characterization of
      individual patient's tumor. At the same time, we realize the great need for
      changes in the financial facets of modem individual treatment, and hoping not to
      hamper the development of new drugs due to the lack of financial solution how to
      make new and expensive drugs available to many patients.

PMID- 19172845
TI  - The scope and requirements related to preclinical and clinical studies of a new
      medicinal product, including biotechnological and biosimilar products.
AB  - The article presents an outline of the requirements concerning the planning of
      preclinical and clinical studies, necessary for the legal approval of a medicinal
      product. It describes the clinical research plan of innovative and generic
      pharmaceutical products, taking into account the specific situations in which the
      assessment of biological equivalence of a generic product is not possible based
      on pharmacokinetic parameters. The article also discusses the guidelines which
      determine the scope of studies which are necessary in the process of registration
      of biotechnological and biosimilar products.

PMID- 19172846
TI  - Phase transfer catalysis in pharmaceutical industry--where are we?
AB  - Basic concept of phase transfer catalysis, its specific features and applications
      in pharmaceutical industry are described.

PMID- 19172847
TI  - Synthetic analogs of natural glycosides in drug discovery and development.
AB  - Secondary metabolites, which have vital environmental and allelopathic functions
      for a host, and long tradition of ethnopharmacological applications preceding
      modern medicinal use, often occur in their native state as glycosides. The role
      of sugar moiety looks completely different from plant physiology point of view
      and from drug discovery and development perspective. Based on a short survey of
      cases, in which structural modification of natural glycone (saccharide part of a
      low molecular weight secondary metabolite) resulted in advantageous
      pharmacological changes, we postulate that glycosides of natural origin can be
      quite promising as drug leads, based on general rules of drug design. In
      particular, polyfunctional sugar moieties offer ample opportunities for almost
      continuous changes in shape, electron density and polarity. By the same token,
      glycosylation of other biologically active natural products, which are not
      natively glycosylated, can be viewed as a tool for tune up of their activity in
      direction of higher efficacy and better selectivity. Despite of considerable
      advances towards turning enzymatic glycosylations into biotechnological
      processes, chemical transformations still remain more practical, particularly for
      synthesis of modified glycosides, both: in research laboratory and in industry.

PMID- 19172848
TI  - A multivariate analysis of patients with brain tumors treated with ATN-RNA.
AB  - Glioblastoma multiforme (GBM) is the most common form of malignant glioma,
      characterized by genetic instability, intratumoral histopathological variability,
      and unpredictable clinical behavior. Malignant gliomas express preferentially a
      number of surface markers that may be exploited as therapeutic targets, such as
      tenascin-C, an extracellular matrix glycoprotein contributes to tumor cell
      adhesion, invasion, migration and proliferation. Disappointing results in the
      treatment of gliomas with surgery, radiation and chemotherapy have fuelled a
      search for new treatment modalities. Here we present the data for 46 patients
      suffering from brain tumor. They were resected and treated with dsRNA (ATN-RNA)
      complementary to the sequence of tenascin-C mRNA. MRI and CT follow up studies
      showed growth tumor delay or lack of its recurrence symptoms, due to inhibition
      of TN-C synthesis. A significant improvement in overall survival (OS) was
      observed without loosing of the quality of life (QOL) of patients. This novel
      therapy based on RNA interference shows a big therapeutical potential. To our
      knowledge intervention with RNAi (iRNAi) is the first protocol of application of
      RNAi in human disease treatment.

PMID- 19172849
TI  - Transcriptional activity of interferon gamma and two subunits of its receptor as
      molecular markers of myocarditis.
AB  - Inflammatory cytokines have an important role in the pathogenesis of myocarditis,
      but still little is known about the importance of interferon gamma (IFNg) in this
      disease. The aim of the study was to evaluate the prognostic value of the initial
      transcriptional activity of IFNg and two subunits of its receptor as measured
      with the use of QRT-PCR and SYBRGreen chemistry in the group of 63 patients with
      clinically confirmed myocarditis who were treated with statin or immunosupressive
      therapy. The initial values of IFNg and the ratio of IFNgRb/IFNgRa were
      statistically different in the analyzed group of patients. The prognostic value
      of IFNg and IFNgRb/IFNgRa was determined by logistic regression analysis.

PMID- 19172850
TI  - Effect of selol on the opioids activity in streptozotocin induced hyperalgesia.
AB  - We examined the effect of the opioid receptor agonists and the effect of an
      antioxidant selol, which is an organoselenium compound on antinociceptive action
      of opioid agonists in diabetic neuropathic pain model. Streptozotocin (STZ)
      induced hyperglycemia accompanied by a prolonged decrease in nociceptive
      threshold is considered a useful model of experimental hyperalgesia. The changes
      in pain thresholds were determined using mechanical stimuli--the modification of
      the classic paw withdrawal Randall-Selitto test. Neither morphine, fentanyl nor
      buprenorphine administered alone in 7 consecutives days modified the STZ induced
      hyperalgesia, whereas selol slightly increased the nociceptive threshold.
      Pretreatment with selol markedly enhanced the analgesic activity of all three
      investigated opioids. Concomitant administration of selol and opioids in
      alleviation of neoplastic pains seems to be justified.

PMID- 19172851
TI  - Evaluation of the expression of transcriptional factor NF-kappaB induced by
      phytic acid in colon cancer cells.
AB  - Over the last years phytic acid, a hexaphosphorylated inositol (IP6) has
      attracted particular attention due to its anti-cancer activity, however, the
      molecular mechanisms of its action have not been elucidated, as yet. The aim of
      this study was to evaluate the influence of phytic acid on the expression of
      genes encoding p65 and p50 subunits of NF-kappaB and of its inhibitor
      IkappaBalpha in human colorectal cancer cell line Caco-2. A kinetic study of p65
      and p50 subunits and IkappaBalpha mRNAs expression was performed on Caco-2 cells
      after treatment with 1, 2.5 and 5 mM IP6 for 1, 6, 12 and 24 h. Quantification of
      the genes expression was carried out using real time QRT-PCR technique. Treatment
      of cells with 5 mM IP6 resulted in a strong increase in IkappaBalpha expression
      at 6 h, 12 h and 24 h. The level of p65 transcript after 1 h was lower in the
      cells exposed to 1, 2.5, and 5 mM IP6 than in the control cells. The increase in
      transcriptional activity of p65 gene in response to 5 mM IP6 after 6 h and 12 h
      was observed. Cells treated for 24 h with 2.5 mM and 5 mM IP6 showed a
      significant decrease in expression of p65 gene. There were no quantitative
      changes in the p50 gene expression in the cells treated with IP6 compared to the
      control cells. High positive correlation between the expression of IkappaBalpha
      and p65 was detected. The results of this study suggest that IP6 primarily
      influences p65 and IkappaBalpha genes expression in colon cancer cells. Changes
      in transcriptional activities of IkappaBalpha and p65 depend on IP6 concentration
      and time of its action.

PMID- 19172852
TI  - Rate of binding of host molecules to artificial receptors formed by self
      organisation of lipidated oligopeptides.
AB  - The arrays of artificial receptors were synthesized and used in the studies of
      binding of triphenylmethyl dyes. Rate of binding of Brilliant Black was
      determined by the measurements of decrease of optical density of dye solution.
      Considering the fast process of removing excess of dye and uniform coloration of
      receptors, Brilliant Black was evaluated as the most versatile reporter dye for
      Indicator Displacement Assay (IDA).

PMID- 19172853
TI  - The new analogues of nitrogen mustard with one, two or three 2-chloroethylamino
      fragments. Reactions with nucleophiles.
AB  - 1,3,5-Triazines substituted with mono-, di, and tri-[4-(2-chloroethyl)piperazin-l
      yl] groups gave products of substitution of chlorine atom when treated with
      ethanol, phenol, butylamine, toluidine,or thiophenol under mild reaction
      conditions.

PMID- 19172854
TI  - Determination of the stereoisomers of racemic alpha-tocopherol in pharmaceutical
      preparations by high-performance liquid chromatography and gas chromatography.
AB  - In the present study we used chiral high performance liquid chromatography and
      gas chromatography to determine the stereoisomers of racemic alpha-tocopherol.
      The Chiralcel OD-H and Silar-100 AT columns were used. Statistical evaluation of
      the results established the precision of these methods.

PMID- 19172855
TI  - Sex dependent antinociceptive activity and blood pressure changes in SHR, WKY and
      WAG rat strains after diclofenac treatment.
AB  - Antinociceptive action of diclofenac (non-opioid analgesic) was investigated in
      male and female normotensive (WKY) and genetically established hypertensive (SHR)
      and normotensive WAG. The drug was administered subcutaneously in doses of 10
      mg/kg body weight and per os 20 mg/kg and 40 mg/kg. Statistically significant
      differences in pain threshold were reported between male and female rats of
      investigated strains. Phase of sex cycle in female rats was determined along with
      the pain threshold level. Arterial hypertension control in WAG and SHR female
      rats performed in parallel showed considerable changes in blood pressure after
      diclofenac administration in the estrus phase. There were several correlated
      effects in blood pressure and pain threshold after drugs administration. The
      results obtained may explain the non-uniformity in antinociceptive action of
      analgesics in both sexes during long-term therapy in different strains.

PMID- 19172856
TI  - Thermochemolysis as the useful method to assess the purity of melanin isolated
      from the human melanoma malignum.
AB  - Melanin formation in pigmented melanoma cells is considered as a target for the
      tumor therapy. The evaluation of potential correlation between melanin structure
      and the tumor type could be also of diagnostic and prognostic importance. One of
      the major problems in structural investigations of natural melanins is the lack
      of appropriate methods, which allow isolation of pure intact pigment. In this
      study the thermochemolysis technique was used to assess the purification grade of
      melanin isolated from the human melanoma malignum cells by two different
      enzymatic methods. Melanin samples were thermally degraded in the presence of
      tetramethylammonium hydroxide and the thermochemolysis products were analyzed by
      gas chromatography/mass spectrometry (GC/MS). Compounds of lipid origin,
      especially fatty acid methyl esters and aliphatic and cyclic hydrocarbons, were
      predominant among pyrolysis products of melanin isolated from the tumor cells by
      method I. In contrast, during thermochemolysis of the pigment sample isolated by
      the method II, mainly eumelanin markers (pyrrole and its methyl derivatives,
      toluene, styrene, phenol, benzyl nitrile and indole) were formed. The comparison
      of pyrolysis profiles of the analyzed samples indicate that method II is more
      efficient for melanoma pigment purification.

PMID- 19172857
TI  - Interactions between glycosyltransferases and 2-deoxy glycosyl derivatives of
      uridine simulated by molecular docking.
AB  - The focus of the present work was to investigate interactions between 2-deoxy
      sugar derivatives of uridine and active sites of N-acetylglucosaminyltransferase
      I and beta-1,4-galactosyltransferase I. The ligand-protein interactions were
      simulated with a docking software (GOLD). The results suggest that the
      synthesized compounds bind the enzyme by a similar mode as the natural substrate.

PMID- 19172858
TI  - Application of confidence intervals to bioanalytical method validation--drug
      stability in biological matrix testing.

PMID- 19172859
TI  - An approach for synthesis of tropinone analogue N-substituted with triazine ring.

PMID- 19172860
TI  - Bortezomib in multiple myeloma: treatment and retreatment. A single center
      experience.

PMID- 19172861
TI  - Molecular properties relevant to bioavailability of tioconazole and its
      derivatives.

PMID- 19172862
TI  - A high-performance liquid chromatography with electrochemical detection for the
      determination of olanzapine in human plasma.

PMID- 19172863
TI  - Polyvinylpyrrolidone-polyurethane interpolymer hydrogel coating as a local drug
      delivery system.

PMID- 19172864
TI  - Electrically enhanced and controlled drug delivery through buccal mucosa.

PMID- 19172865
TI  - Efficacy and safety of thalidomide in the treatment of multiple myeloma.

PMID- 19172866
TI  - Comparison of properties of cyclic and linear glycine derived structures and
      their phosphorus analogues--theoretical studies.

PMID- 19172867
TI  - Examination of antibacterial and antifungal activity of selected non-antibiotic
      products.

PMID- 19172868
TI  - Validation of an analytical procedure--control of residual solvents in
      pharmaceutical substance.

PMID- 19172869
TI  - Biological activity of methyl 2-[5-oxo-3,4-di-(2-pirydyl)-1,4,5,6-tetrahydro
      1,2,4-triazine-6-ylidene] acetate.

PMID- 19172870
TI  - Closely related isoxazoles may exhibit opposite immunological activities.

PMID- 19172871
TI  - Triazole derivatives with antifungal activity: a pharmacophore model study.

PMID- 19172872
TI  - [Mycoplasma M. arginini infection induces constitutive activation of NF-kappaB
      and inhibits apoptosis in cells expressing toll-like receptors TLR2/6].
AB  - NF-kappaB is one of the main transcriptional factors that is responsible for cell
      survival under stresses. It was shown that various species of mycoplasma and
      their structural components were able to stimulate NF-kappaB activation as a
      result of their interaction with specific toll-like receptors on eukaryotic cell
      surface. Based on these studies, we suggested that activation of NF-kappaB in
      response to mycoplasmal infection could enhance the resistance of infected cells
      in response to proapoptotic stimuli. In this study we showed that infection of
      cells expressing toll-like receptors TLR2/6 with mycoplasma M. arginini leaded to
      suppression of apoptosis induced by chemotherapeutic agents (cisplatin, 5
      fluorouracil, taxol).

PMID- 19172873
TI  - [A comparative study of the role of the yadA, invA, and psaA genes in the
      pathogenicity of Yersinia pseudotuberculosis].
AB  - The roles of yadA, invA, and psaA genes introduced into the genetic background of
      the Y. pseudotuberculosis strain possessing the large p VM82 plasmid in virulence
      and invasion capacity were studied. Isogenic single mutants as well as double and
      multiple mutants of these genes were constructed and used. LD50 was used as a
      measure of virulence and the estimation of the ability to invade mammalian cells
      and the effect of infection on the weight changes of infected mice were used as
      additional indicators of pathogenicity. It was shown that the YadA had a major
      effect on the bacterial virulence when compared with the effects of PsaA and
      InvA. InvA appears to mediate the main pathway of the cellular invasion. YadA is
      responsible for the weight loss after infection of mice with sublethal doses of
      Y. pseudotuberculosis. The effects of YadA on virulence and of InvA on bacterial
      invasion were independent of the expression of the other genes studied. To our
      knowledge, this study showed for the first time the direct involvement of YadA in
      the virulence of Y. pseudotuberculosis in mice. Further pathomorphological
      studies are required to reveal the differences in the pathogenesis of
      pseudotuberculosis caused by yadA mutants or yadA+ bacteria of Y.
      pseudotuberculosis.

PMID- 19172875
TI  - [Determining drug resistance of the clinical strains of Mycobacterium
      tuberculosis to pyrazinamide].
AB  - Description of the pyrazinamide-resistant clinical strains of M. tuberculosis
      derived from sputum of patients treated in TB clinics in Tula was made (June,
      2001 - July, 2002). It was demonstrated that 30.3% (n = 91) strains were
      resistant to pyrazinamide. It was found out that these strains were resistant to
      other antituberculosis drugs in most cases. The method of PCR-sequencing was used
      to find the mutations in the gene pncA determining resistance to pyrazinamide. 44
      different types of mutations localized in 28 codons were detected. The
      predominance of the mutations in 57 (13.2%), 63 (7.7%), 97 (7.7%), 12 (6.6%), 103
      (6.6%) codons and in -11 (6.6%) promoter ofp ncA was observed in the pyrazinamide
      resistant strains. Several new mutations determining resistance of the clinical
      strains of M. tuberculosis to pyrazinamide were described. A high correlation
      between resistance of mycobacteria to pyrazinamide and activity of pyrazinamidase
      was observed.

PMID- 19172874
TI  - [Mechanism of interaction of tumor necrosis factor (TNF-alpha) of macroorganism
      with the Salmonella enterica cells (ser. Typhimurium)].
AB  - The goal of this work was to elucidate the mechanism of direct interaction of
      bacterial cells with tumor necrosis factor (TNF-alpha; cytokine). It was shown
      earlier that this interaction facilitated activation of bacterial growth and
      recultivation of non-cultivated forms in vitro and in vivo. It was shown in
      experiments with mice deficient in the genes encoding eucaryotic TNF-alpha
      receptors and infected with salmonella that addition of exogenous TNF-alpha to
      suspension of infection cells caused a one-day acceleration in the infection
      start (bacteria planting from spleen) in both knockouted and control mice
      relative to the same animals infected with the same bacteria without cytokine.
      Thus, bacteria are able to interact with cytokine even in the absence of
      eucaryotic receptors. Specificity of the bacterium-cytokine interaction and
      bacterial protein EF-Tu mediating direct interaction of bacteria with cytokine
      were identified using the method of immobilization of recombinant protein TNF
      alpha-spacer-CSD on cellulose.

PMID- 19172876
TI  - [Construction of the vector based on the CELO avian adenovirus genome providing
      enhanced expression of secreted alkaline phosphatase gene in a non-permissive
      system in vitro and in vivo].
AB  - Aviadenovirus CELO is a promising vector for gene delivery to eukaryotic cells,
      including mammalian cells. In the present state of affairs, it gives a chance to
      apply recombinant adenoviruses CELO against animal pathogens. High expression
      level of transgene consisting of virus vector is necessary to reach protective
      humoral and T-cell immune answer. One of the approaches to enhance the expression
      level of transgene consisting of viral vectors is inclusion of addition 5'- and
      3'- untranslated regulatory elements (PARS, IRES, WPRE) to the expression
      cassette. In this work, 5'-untranslated regulatory elements of major late
      transcription unit of CELO genome (a bipartite leader and gene hexon leader) were
      used for construction of the expression cassette consisting of the recombinant
      adenovirus CELO to provide high expression level of reporter gene of secreted
      alkaline phosphatase in nonpermissive cell system. It was shown in our
      experiments that the obtained recombinant adenovirus CELO was characterized by
      enhanced (2.4-3.5 times) expression level of reporter gene in transduced
      mammalian cells in vitro and in vivo.

PMID- 19172877
TI  - [Molecular and genetic characterization of allelic variants of microsatellite
      loci in parthenogenetic Caucasian rock lizards Darevskia armeniaca (Lacertidae)].
AB  - Using a pair of primers selected for the loci deltau 215, deltau 281, and deltau
      323 of Darevskia unisexualis monolocus PCR analysis of orthologous loci was
      carried out in populations of the related parthenogenetic species D. armeniaca
      and in populations of bisexual parental species D. valentini and D. mixta. It was
      shown that the studied loci were polymorphic and represented in populations of D.
      armeniaca by several allelic variants. We cloned and sequenced PCR amplification
      products of the allelic variants of deltau 215, deltau 281, and deltau 323 loci.
      It was found that allelic differences of microsatellite loci were caused by
      variation in a number of tandem repeats in the microsatellite clusters and point
      mutations in the flanking regions. Interspecies comparison of the orthologous
      locus deltau 215 between parthenogenetic species D. armeniaca and parental
      species showed that two allelic variants of deltau 215 in D. armeniaca were
      inherited from the parental bisexual species D. mixta and D. valentini. The third
      allelic variant was not found in parental species and appeared because of
      mutation processes in genome of parthenospecies. For the first time, the
      information about the molecular nature of allelic polymorphism of these
      microsatellite loci of parthenogenetic species D. armeniaca was received in this
      study.

PMID- 19172879
TI  - [Hardware-software system for noninvasive electrocardiographic examination of
      heart based on inverse problem of electrocardiography].

PMID- 19172878
TI  - [Distribution of mutations in the rpoB, katG, inhA, ahpC gene of rifampicin and
      isoniazid resistant M. tuberculosis strains isolated in Kyrgyz Republic].
AB  - The aim of this work was to evaluate the prevalence mutations in the rpoB, katG,
      inhA, ahpC gene of rifampicin and isoniazid resistant M. tuberculosis (Tb)
      isolates from Kyrgyz Republic using OA Biochip MDR. In the rifampicin-resistant
      strains, the mutations were identified in the codons 531, 526, 516, 511, 513,
      512, 533, and 522. The most prevalent point mutations were Ser531RLeu at the
      codon 531 (59.7%). Resistance to INH was associated with mutations found in the
      katG gene (94.5%), inhA gene (3.5%), and ahpC gene (1.0%). The most prevalent
      mutations were SerRThr at the codon 315 (93.0%). The rifampicin and isoniasid
      resistance of the M. Tb strains isolated in Kyrgyzstan is associated mostly with
      Ser531RLeu mutation of the rpoB gene, Ser315RThr mutation of the katG gene, and
      InhT15 mutation.

PMID- 19172880
TI  - [A method for compensation of the cardiac rhythm variability in sphygmogram
      analysis].

PMID- 19172881
TI  - [Intellectual pulse express-diagnosis of the state of human cardiovascular
      system].

PMID- 19172882
TI  - [Radiation load associated with target-oriented and panoramic X-ray examination
      using portable X-ray equipment].

PMID- 19172883
TI  - [Development of a device for electrothermometry with cold test in patients with
      pneumatic hammer disease].

PMID- 19172884
TI  - [On the necessity to develop a special list of medical criteria for the
      qualifying sign "mental disorder"].
AB  - The authors propose and discuss approaches to the expert evaluation of the
      severity of harm to the health in the form of mental disorder associated with the
      traumatic impact. The following qualifying signs of the degree of harm to the
      health included in the current legislation are considered in terms of forensic
      psychiatry: "life-threatening harm" (Criminal Code of the Russian Federation,
      article 111) and "length/brevity of impairment of the health" (Criminal Code of
      the Russian Federation, articles 112, 115). The well-grounded proposals of
      changes in the existing legislation envisage that the qualifying sign "permanent
      maladjustment" should be introduced into the corresponding legal innovations of
      the Criminal Code as useful for the forensic medical examination of victims with
      mental disorders. Substantive definition of such notions as "transient
      disadaptation", "permanent maladjustment" and degree of its manifestation (mild,
      moderate, severe) are given.

PMID- 19172885
TI  - [Differential diagnosis of subdural liquor accumulation in recurrent
      craniocerebral injury].
AB  - Criteria are proposed for the diagnosis of the origin and time- lapse of subdural
      accumulations of liquor in patients with repeated craniocerebral injury. The set
      of this criteria includes specific features of association and relative position
      of subdural liquor accumulations, their volume, and intracranial manifestations
      of primary and repeated craniocerebral injuries. Algorithms and nomograms have
      been developed in the course of the study allowing for accurate differentiation
      between subdural liquor accumulations as consequences of primary and repeated
      craniocerebral injuries. The results of the study have implications for practical
      forensic medical evaluation of repeated craniocerebral injuries with subdural
      liquor accumulation.

PMID- 19172886
TI  - [Identification of the type of external impact based on the analysis of fracture
      site morphology in the long tubular bones of the lower extremities].
AB  - Morphological structure of the destroyed compact layer at the fracture site in
      long tubular bones was examined after various forms of external disturbance.
      Different load intensity was shown to cause qualitatively different changes in
      the texture of the affected bone tissue "at opens up the possibility for
      differential diagnosis of the impact and pressure on the fractured surface.

PMID- 19172887
TI  - [Forensic medical evaluation of age-related changes of elastic properties of the
      large arteries].
AB  - Quantitative characteristics of elastic properties of the human aorta, carotid,
      femoral, and humeral arteries have been obtained in the study of autopsy
      materials. Their mathematical analysis revealed a statistically significant
      decrease of arterial wall elasticity with age. It is concluded that these data
      can be used to develop a method for the objective age determination for the
      purpose of forensic medical examination.

PMID- 19172888
TI  - [Forensic medical aspect of the maternal mortality problem].
AB  - The relevance of maternal mortality estimation in the context of forensic medical
      examination is emphasized. Results of the qualitative analysis of the materials
      of such examinations undertaken with regard to the issue of maternal mortality
      (MM) in 2000-2007 are presented. Examples of diagnostic failure are considered as
      a cause of deficient medical attendance in gynecological and obstetric practice
      and in the treatment of iatrogenic (instrumental) complications during and after
      endotracheal intubation.

PMID- 19172889
TI  - [Postnatal differential diagnosis of combined birth injury in newborn infants].
AB  - Constructional defects of skull base synchondroses related to a fatal birth
      injury result only from bottom-upwards pressure of the vertebral column and
      always combine with a crack or displaced fracture of the sapheno-occipital
      suture. A postnatal injury having the form of occipital synchondrosis fracture
      occurs in case of a local impact on the cervico-occipital region and is not
      associated with a shear strain of lateral synchondrosis and any damage to the
      sapheno-occipital suture. The spinal birth injury is due to the axial load on the
      vertebrae in combination with excessive bending and rotation. The postnatal
      spinal trauma results from neck compression and closure of the mouth and nose
      openings. It can be either flexural or extensive with a rotational component or
      without it; in any case, it shows no signs of axial load on the vertebrae. In
      case of a postnatal combined craniospinal injury in a newborn infant, unlike
      birth trauma, there are no constructive shear strains with the rupture of lateral
      synchondroses of the major portion of the occipital bone and synchondrosis
      between the main part of the occipital bone and the sphenoid bone.

PMID- 19172890
TI  - [Information value of electrolytes, glucose, and urea in pericardial liquid in
      different terminal conditions].
AB  - The informative worth of sodium, potassium, calcium, magnesium, glucose, and urea
      levels in the pericardial liquid is analysed. The values of these parameters in a
      terminal disease of cerebral origin may testify to the absence of disturbances of
      energy and protein metabolism or electrolyte disbalance in the myocardium.
      Disturbances of myocardial electrolyte balance, energy and protein metabolism
      develop in cardiac, pulmonary, and mixed type terminal conditions. Cardiac arrest
      is associated with impaired myocardial conduction.

PMID- 19172891
TI  - [Estimation of the body length from the hand bones in adult subjects].
AB  - A method for estimation of the body length from the wrist bones in adult subjects
      is reported for the first time. Carpal, metacarpal, and phalangeal bone length in
      108 skeletons of Caucasoid subjects (stored in the collections of the Department
      of Anthropology, M V. Lomonosov Moscow State University, and Museum of
      Anthropology, Sankt Peterburg State University) was measured to the nearest 0.1
      mm by the method of R. Martin. The SPSS programs were used to calculate multiple
      regression equations allowing for the determination of the body length from the
      lengths of carpal bones (to the accuracy within +/- 46.1 mm), metacarpal bones 1
      V (to the accuracy within +/- 56.7 to 48.6 mm), their combinations (to the
      accuracy +/- 49.1 to 47.9 mm), and the longitudinal size of radii I-V (to within
      +/- 50.8-44.4 mm). The precision of the estimation was as high as +/- 3.5 mm
      provided all the wrist bones were available for the measurement. It is concluded
      that the results of verification of this method may be applied in the practice of
      forensic medicine.

PMID- 19172892
TI  - [Peculiarities of sexual development in Caucasoids and Ural Mongoloids in
      Northern Russia].
AB  - A review of the domestic scientific literature concerning forensic medical
      aspects of the girls' pubertal development is presented. The interplay of various
      social factors is shown to influence the rate of sexual maturation and the age at
      which puberty begins. Racial differences of these parameters are demonstrated. It
      is concluded that they need to be further studied and taken into consideration in
      forensic medical evaluation of the time of sexual maturity.

PMID- 19172893
TI  - [Study of the specific features of the tooth and jaw system of Dagestanians and
      Armenians for personality identification].
AB  - The objective of this study was to elucidate anatomic and morphological features
      of the dental system in several ethnic groups comprising Dagestan population
      (Laks, Avars, Dargins) and the population of Armenia (Armenians) for the
      establishment of their ethno-racial identity. Clinical, morphometric, and X-ray
      studies were conducted; the data obtained were treated statistically. It was
      demonstrated that the ethnic and racial identity of the population groups of
      Dagestan and Armenia included in the study can be determined based on selected
      characteristics of their dentoalveolar system. Moreover, these characteristics
      may be of some use for personality identification.

PMID- 19172894
TI  - [The development and application of an immunoenzyme assay kit for the detection
      of compounds of the opiate family in human biological liquids].
AB  - Monoclonal antimorphine antibodies both free and conjugated with horse- radish
      peroxidase have been raised and used to develop an assay kit for the detection of
      narcotic opiate-based drugs by an immuno-enzyme assay (IEA). The kit contains all
      ingredients necessary for the enzymatic reaction. A total of 215 urine and blood
      samples were analysed using the new kit. The results were compared with the data
      obtained by thin layer chromatography and high-performance liquid chromatography.
      False negative results were absent while false positive (inconclusive) results
      were recorded in three cases, probably due to the fact that sensitivity of IEA is
      higher than that of control methods. It is concluded that the kit may be used in
      laboratory screening studies for detecting opiates in biological fluids.

PMID- 19172895
TI  - [Anatomic approach to the sphenooccipital synchondrosis in newborns and infants
      with craniocerebral injury].
AB  - An anatomic approach is developed to sphenooccipital synchondrosis in newborn
      infants and nurslings. After removal of the squamous portion of the occipital
      bone by the method of Medvedev, opening of the cerebrospinal canal, removal of
      the spinal cord and hypophysis, two parallel cuts converging at an angle of
      approximately 90 degrees were made with a dissecting blade saw along both sides
      of sella turcica towards the anterior edge of the great occipital foramen to
      transect the sphenoid bone and main part of the occipital bone. The resulting
      osteochondrous fragment showed up defects in synchondrosis including consolidated
      ones.

PMID- 19172896
TI  - [The problem of poisoning with lithium compounds--the past and the present].

PMID- 19172897
TI  - [Forensic medical personnel of Moscow and philanthropy].

PMID- 19172898
TI  - [Scientific and Practical conference "Organization of cooperation and activities
      of forensic medical experts and clinicians for the expert evaluation of
      craniocerebral injuries". Sankt-Peterburg, 27-28 March, 2008].

PMID- 19172899
TI  - [The III Inter-regional Scientific and Practical Conference of the Association of
      Non-commercial Forensic Medical Institutions, "Forensic medical expertise of
      cadaver in Federal Forensic Medical Institutions of Health Care Administrative
      Organs of Southern Federal District of the Russian Federation: organisation,
      problems and ways of improvements.", Kislovodsk, 24-25 January, 2008].

PMID- 19172900
TI  - [Avian influenza vaccines].
AB  - The review gives data on the designing of avian influenza vaccines and the
      preparation of human safe vaccine strains from the highly virulent strains of
      these viruses. It considers activated and live vaccines, promising adjuvants for
      vaccines, as well as recombinant, virus-vector, and DNA vaccines and virus-like
      particles. The results of a number of clinical trials of avian influenza vaccines
      are examined. Analysis of the data published leads to the conclusion that cell
      culture-based whole-virion vaccines with adjuvants are promising in combating
      avian influenza.

PMID- 19172901
TI  - [Site-directed modification of caspase cleavage site regions in avian influenza
      virus proteins].
AB  - A reverse genetics approach was applied to generate variants of avian influenza
      virus A/FPV/Ro/34 (H7N1) containing mutations in the caspase cleavage sites of NP
      and M2 proteins. Mutation Gly16 --> Asp in avian virus NP made this protein
      (NPgd) sensitive to caspases, like human virus NP, and permitted its cleavage in
      infected cells. Mutant recombinant virus NPgd was able to replicate and stably
      carried Gly --> Asp mutation during passages in cultured cells, chicken eggs, and
      chickens. This variant was found to have significantly decreased virulence for
      chickens comparatively to wild type recombinant virus (wtr). Virus variants
      characterized by deletion Gly16 in NP (NPdel) and mutated caspase cleavage site
      VDVDD87 --> VNVND87 in M2 (M2nn) protein were shown to lack intracellular caspase
      dependent cleavage of NP and M2, respectively, and to retain their ability to
      replicate in different hosts. Variant NPdel, like wide type virus, displayed a
      high chicken virulence whereas M2nn, like NPgd one, was found to possess a low
      virulent phenotype. The findings suggest that the mutations altering natural
      caspase cleavage motifs in NP and M2 do not restrict virus replication ability
      but can significantly reduce the virulent potential of the mutant viruses.
      Recombinant virus variants with altered caspase cleavage motifs could be proposed
      as a matrix for the design of live recombinant vaccines.

PMID- 19172902
TI  - [Relationship of nuclear import of influenza virus nucleoprotein polymers to
      their conformational status].
AB  - It has been earlier shown that in the cells infected with influenza virus, the
      molecules of nucleoprotein (NP) are polymers that differ in their conformational
      maturity and stability. The present investigation has studied the ability of
      different conformational forms of NP polymers to migrate into the nucleus.
      Conformationally mature compact NP oligomers are shown to predominantly import
      into the nucleus. In contrast, unstable, loose, and conformationally immature NP
      multimers accumulate in the cytoplasm and do not migrate into the nucleus. The
      present investigation is the first evidence for that that the conformational
      maturity of influenza virus NPs is essential for their nuclear traffic and,
      hence, for participation in the transcription and replication of viral genomes.

PMID- 19172903
TI  - [Phylogenetic analysis of the nucleotide sequences of Chatanga virus strains, the
      new representative of California encephalitis serocomplex, isolated in different
      regions of the Russian Federation].
AB  - The complete nucleotide sequences of the S segment and the fragments of M and L
      segments (on 900 and 410 nucleotides, respectively) were determined in 14
      California encephalitis serocomplex (CES) strains isolated from different regions
      of the Russian Federation. Phylogenetic analysis by the sequences of genomic S,
      M, and L segments indicated that all Russian strains were an individual
      independent CES virus. The new virus is named Chatanga for the place of isolation
      of one of the strains. Two genetic groups of Chatanga virus have been identified.
      Snowshoe hare (Lepus americanus) virus and La Crosse virus are closest to
      Chatanga virus among CES viruses.

PMID- 19172904
TI  - [Infection of pigs with influenza A/H4 and A/H5 viruses isolated from wild birds
      on the territory of Russia].
AB  - Pigs were intranasally infected with avian influenza A/H5 (H5N1, H5N3) and A/H4
      (H4N6, H4N8) viruses in mono- and coinfection. Infection with both apathogenic
      and pathogenic strains caused no clinical manifestations. A virus and/or
      fragments of its genome retained in nasopharyngeal fluid as long as 6-8 days
      after infection. During monoinfection, the structure of the hemagglutinin (HA)
      receptor site of isolates from the pigs infected with A/H5N1 strains
      (A/chicken/Kurgan/3/2005, A/duck/Russia/5354-vac/2005) and A/H5N3
      (A/duck/Primorje/2633/01) remained unchanged during 6-7 days. When two animals
      infected with avirulent A/H5N3 viruses (A/duck/Primorje/2633/01,
      A/duck/Altai/1285/91) that differed in immunogenic properties were kept together,
      the A/duck/Altai/1285/91 virus that induced a later IgG generation was prevalent
      in the nasopharyngeal fluid of both animals. Moreover, 4 significant nucleotide
      replacements were detected in the HA gene on days 7-8. Infection of pigs with
      avian influenza A/H4 viruses yielded the similar results. The joint keeping of
      animals infected with Algarganey teal/Astrakhan/309/102 (H4N8) strain and A/ musk
      beaver/Buryatia/944/00 (H4N6) isolated from musk beaver exhibited fragments of "a
      variant" of the identical structure in the nasal swabs of both animals on days 7
      8. A nucleotide sequence from 37 nucleotide replacements differing from both
      baseline sequences was revealed in the HA 364-1045 gene region. The amino acid
      sequence of the variant was similar to Algarganey teal/Astrakhan/3091/02, other
      than one position 264 < Lys > (numeration by H3), which coincided with the A/
      musk beaver/Buryatia/1944/00 strain. The latter induced the antibody generation
      on day 5 after infection while the A/garganey teal/Astrakhan/3091/02 strain did
      only on day 14. It is possible that under co-circulation of two different
      influenza A viruses, the virus causing a slower development of an immune response
      showed a higher probability of transiting to another host (specimen) and changing
      the HA receptor site in the organism of a new host.

PMID- 19172905
TI  - [Nucleotide sequence analysis of the NSP4 gene from group A rotaviruses isolated
      in Nizhni Novgorod].
AB  - The complete nucleotide sequences of the NSP4 gene from Russian isolates of Group
      A rotaviruses with different G[P] types obtained in Nizhni Novgorod have been
      first ascertained. They belong to their affiliation to three NSP4 (A, B, and C)
      of the 5 known genotypes. Eleven strains had NSP4 genotype. Phylogenetic analysis
      based on the complete nucleotide sequences of the NSP4 gene revealed the sequence
      homology of G1P[8] viruses with the strains circulating in Scandinavia and that
      of the G3 type viruses with the strains from South-Eastern Asia. The rotavirus
      strains G1, G3, G4, and P[8] demonstrated the homology with porcine rotavirus
      strains, while the strains G3P[6], G3P[9], and G2P[4] did the homology with
      bovine rotavirus strains. There was an unusual strain of human rotaviruses G3P[9]
      genetically related to feline rotaviruses.

PMID- 19172906
TI  - [Role of a host in spontaneous recovery from viral hepatitis C: genetic
      predetermined factors].
AB  - The impact of both congenital and specific human immune responses on the invasion
      of viruses is determined by a broad spectrum of genetically determined
      parameters. The review attempts to characterize the influence of genetic
      determinants on the outcome of human hepatitis C viral (HCV) infection. The
      increased rate of convalescence is associated with female sex and white
      ethnicity. Hereditary immune disorders/deficiency lead to the reduced probability
      of spontaneous convalescence and the complicated course of a chronic stage of the
      disease. The carriage of some HLA haplotypes and gene alleles, which determine
      the development of an immune response following the Th1 or Th2 type, is essential
      in predicting both the outcome of acute HCV infection and the course of chronic
      hepatitis C. Specifically, the higher elaboration of IFN-gamma and IL-12 which
      specify a Th1 immune response facilitates the good outcome of HCV infection. At
      the same time, the increased generation of Th2-orienting IL-6 and IL-10
      predisposes to the chronic course of the disease. In recent studies, the outcome
      of the infection is also associated with the polymorphism of genes, encoding for
      low-density lipoproteins and complement type 1 receptors, with other genes
      determining the development of a congenital immune response and a specific one.
      The understanding of genetic predisposition of the outcome of HCV infection and
      the possibility of its prediction may make a considerable contribution to the
      definition of treatment policy for viral hepatic C.

PMID- 19172907
TI  - [Identification of porcine parvovirus and virus-specific antibodies by polymerase
      chain reaction and enzyme immunoassay].
AB  - Porcine parvovirus infection (PPVI) caused by a small non-enveloped virus
      (porcine parvovirus, PPV) is responsible for serious reproductive dysfunctions in
      sows. In the Russian Federation, the approved diagnostic methods for
      determination of parvovirus antigen and virus-specific antibodies are
      hemagglutination and hemagglutination-inhibition tests, respectively. The present
      paper gives the results of developing diagnostic tests to reveal porcine
      parvovirus by polymerase chain reaction and its antibodies by recombinant protein
      based indirect enzyme immunoassay. The developed tests supplement a battery of
      diagnostic methods and specify some disputable results obtained by classical
      methods.

PMID- 19172908
TI  - [Stimulus set and response set in task switching: a comparison using ERP].
AB  - Event-related potential (ERP) and reaction time (RT) were recorded to investigate
      the time course of processes involved in set switching. The cued set-switching
      paradigm required participants to switch stimulus task sets between male and
      female face-images memorized as targets prior to a trial block and response task
      sets between two stimulus-response mappings for each stimulus task. Replicating
      previous findings, an RT switch-cost was found when compared with set-repeat
      trials. The RT was also prolonged for a stimulus task requirement of memory
      comparison with two-face targets rather than one face. A similar prolongation
      with memory comparison was observed in P3b latency, which showed no switch
      effect. The switch effect was observed for the onset latency of stimulus-locked
      lateralized readiness potential (LRP), measured as an index of commencement of
      motor processes after response selection. The response-locked LRP indicated that
      the final process of motor execution itself was not modified by set switching.
      The processes producing the stimulus-locked LRP switch cost, associated with
      response task set, were discussed in terms of two hypotheses, exogenous
      reconfiguration and carryover.

PMID- 19172909
TI  - [Cognitive dimensions used in rating work performance].
AB  - This study explored the cognitive dimensions used by individuals in judging work
      performance based on the individual scale methodology of Hayashi, Ohashi, &
      Hirooka (1983). The participants were fifteen undergraduate students and nine
      workers. First, the participants described the characteristics of eight high
      performers and eight low performers whom they had worked with. Second, from these
      characteristics, they selected twenty characteristics that they considered as
      determinants in judging whether performers are superior or inferior. Third, using
      an individual scale consisting of the selected characteristics, they rated
      sixteen high performers and sixteen low performers. Factor analyses were
      conducted for each participant's ratings on the individual scale. The results
      suggested that three or four dimensions were generally used in judging
      performers, although there were individual differences in the number of
      dimensions used. Undergraduate students judged performers using more cognitive
      dimensions than workers did. The contents of the cognitive dimensions were
      relevant to technical skill, work attitude, cognitive ability, motivation,
      interpersonal competence, leadership, and personality. Undergraduate students
      used fewer cognitive ability dimensions and more personality dimensions than
      workers used.

PMID- 19172910
TI  - [Regulating factors of intention and experience with co-production related to
      local government administration].
AB  - This study examined the regulating factors of intention and experience with co
      production related to local government administration. The result of a survey for
      211 adults showed that their intention to participate in co-production was
      determined by "contact/information disclosure expectations" for local government
      employees, dissatisfaction with local government, communication with the
      neighborhood, and the number of organizational affiliations in the community. Of
      these factors, the number of organizational affiliations also determined
      experiences with co-production. Co-production was promoted by increased
      affiliative expectations for local government employees and ties in the community
      for action.

PMID- 19172911
TI  - [Development of a vulgarity scale based on Ortega's "The revolt of the masses"].
AB  - This study developed a scale measuring the spiritual vulgarity of the masses,
      based upon Ortega's "The revolt of the masses" (1957). A questionnaire was
      constructed with forty items, based on Ortega's descriptions of the
      characteristics of the spiritual vulgarity of the masses. The questionnaire was
      completed by 200 university students. The results of factor analysis of the
      vulgarity measurements yielded two subscales; autistic attitude and contumelious
      attitude. The two scales were correlated with other existing measures of social
      values, which was further evidence of validity.

PMID- 19172912
TI  - [No difference found between cognitive processing of self-face (self-name) and
      other's face (other's name) using a priming task].
AB  - This study investigated differences between cognitive processing of an
      individual's own face or name and another's face or name based on the interactive
      activation and competition (IAC) model of Burton, Bruce, & Johnston (1990). In
      Experiment 1, the self-face and faces of famous persons were used as target
      stimuli, and the self-face, self-name, faces or names of the famous persons were
      used as prime stimuli. In Experiment 2, self-name and names of famous persons
      were used as target stimuli. Participants were instructed to judge whether the
      target was male or female as quickly and accurately as possible. The results
      showed that reaction time for the targets was fastest when the prime was
      identical with the target in both experiments. This pattern was seen for both
      self and others. These results suggest that there is no difference between the
      cognitive processing of the self-face (name) and another's face (name). We
      proposed a modified framework for the role of face and name in the IAC model.

PMID- 19172913
TI  - [Relationship between recognition judgments and confidence ratings for repeated
      test items].
AB  - Eighty-nine participants performed a set of recognition judgment and confidence
      rating tasks twice. Half of the new items presented in the second task had
      already presented as old items to the participants in the first task. Analysis of
      the second task responses, showed a positive correlation between confidence and
      performance for the old items, and a negative correlation for the new items. In
      particular, a strong negative correlation was observed when items presented in
      the first task were presented as "new" in the second task. This negative
      correlation reflects "source monitoring error" where the participants falsely
      recognized the items in the first task as those presented in the second, because
      they were unaware of making source misattributions.

PMID- 19172914
TI  - [Relationship among weblog authors' target audience, contents, and types of
      interpersonal communication].
AB  - Weblogs are one of the most popular personal websites in Japan, where entries are
      made in journal style and displayed in reverse chronological order. This study
      examined the relationship between weblog authors' target audience (i.e.,
      orientation) and the actual situations depicted in their weblogs by combining a
      questionnaire survey of the authors with an analysis of their weblog content
      data. Based on a questionnaire survey of 736 Japanese weblog authors, their
      target audience was divided into four clusters: (a) general public, (b) self, (c)
      self and offline friends, and (d) various others. To assess the actual situations
      depicted in their weblogs, the amount of happy and unhappy emotional expression
      in their writing and the frequency of interpersonal communication (comments,
      bookmarks, and trackbacks) were calculated from their log data. The results
      suggested that weblog authors wrote different types of content and used different
      types of communication depending on their audience, whereas the weblog content
      itself still showed the diary-like characteristic of personal daily-life records.

PMID- 19172915
TI  - [Construction of a Japanese version of the "Regret and Maximization Scale" in
      decision making].
AB  - This study developed a Japanese version of the "Regret and Maximization Scale" in
      decision making, which was originally constructed by Schwartz, Ward, Monterosso,
      Lyubomirsky, White, and Lehman (2002). This scale measures assess the tendency to
      experience regret, and individual differences in the desire to maximize or to
      satisfy. In Study 1, the original version of the "Regret and Maximization Scale"
      was translated into Japanese and administered to 307 Japanese university students
      responded the scale. Factor analysis did not replicate the finding of Schwartz et
      al. (2002). In Study 2, we developed new items, and constructed a "Japanese
      Version of the Regret and Maximization Scale", based on the interpretation of the
      factor analysis in Study 1. This new version of the scale was administered to 163
      Japanese university students. The result of factor analysis and reliability
      analysis indicated that this "Japanese Version of the Regret and Maximization
      Scale" had a considerably high Cronbach's alpha and conceptual validity.

PMID- 19172916
TI  - Relationship between smoking and periodontal probing pocket depth profile.
AB  - The purpose of the present study was to investigate if the periodontal probing
      pocket depth profile differs significantly between smokers and non-smokers as
      well as within the smoking group. Subjects born 1940-1943 were collected from a
      computer database at a specialist clinic of periodontology. The patients included
      consisted of 293 individuals between 57 and 64years of age examined by nine
      periodontists. The periodontal probing depth at site level, age, gender and
      smoking habits were collected from the database. Former smokers and patients with
      an uncertain history of smoking habits were excluded. The smokers were stratified
      into three groups according to the daily consumption of cigarettes (1-10 cig/day,
      11-20 cig/day, > 20 cig/day). The relative frequencies of periodontal probing
      pocket depths of 4-5 mm and > or = 6 mm were calculated and these two categories
      were used in the analyses. The partial correlation coefficients between smoking
      and the percentage share of periodontal pocket depths in different tooth regions
      were calculated by using multiple regression analyses. The smokers had
      significantly deeper periodontal pockets compared to the nonsmokers. The
      correlation between smoking and the percentage share of palatal periodontal
      pockets > or = 6 mm was significant. The percentage share of palatal pockets > or
      = 6 mm was significantly increased for subjects who smoked > 20 cigarettes per
      day (25%) compared to non-smokers as well as compared to subjects with a daily
      consumption of 1-20 cigarettes per day. This difference was significant within
      all tooth groups in the upper jaw. The results support the hypothesis that
      smoking has a local effect on periodontal pocket depth beside the systemic
      effect.

PMID- 19172917
TI  - Treatment of smarting symptoms in the oral mucosa by appliance of lingual acrylic
      splints.
AB  - The aim of the present study was to evaluate the relieving effect on smarting
      symptoms in the oral mucosa by the use of lingual acrylic splints. Recruited for
      the study were 53 persons, 48 women and 5 men, with smarting symptoms in the oral
      mucosa, not associated with general disease, and with signs of erythema, most
      often on the apex of the tongue, and/or crenated tongue. Symptoms were registered
      from the tongue in 49 cases, the palate in 28 cases and the lips in 15 cases. A
      lingual acrylic splint was applied in the lower jaw behind the front teeth, not
      covering the occlusal surfaces and it was kept in the mouth day and night. At an
      average the splint was used in 8 months. A group of 10 women was recruited for
      comparison. These women were just instructed to avoid tongue pressing for at
      least a two month period. All patients were asked whether the treatment affected
      the symptoms and they registered their opinion on a 100 mm VAS line with end
      effect points "not helped at all/deteriorated" and "now completely without
      symptoms". On the question whether the treatment had affected the symptoms, the
      average result was 55 mm and median value 64 mm. The treatment results were
      somewhat better among those with moderate initial symptoms compared to those with
      severe symptoms. Interestingly, in the group for comparison, symptom VAS values
      improved significantly from 60 to 41 mm (P < 0.05). CONCLUSION: Treatment of
      smarting symptoms in the oral mucosa may to a great extent be relieved by the
      application of an acrylic lingual splint. However, before using this splint
      method, an effort should be made to make the patient actively avoid tongue
      pressure.

PMID- 19172918
TI  - Impaired jaw function and eating difficulties in whiplash-associated disorders.
AB  - Eating requires mouth opening, biting, chewing and swallowing and should be
      performed without dysfunction or pain. Previous studies have shown that jaw
      opening-closing movements are the result of coordinated activation of both jaw
      and neck muscles, with simultaneous movements in the temporomandibular, atlanto
      occipital and cervical spine joints. Consequently, it can be assumed that pain or
      dysfunction in any of the three joint systems involved could impair jaw
      activities. In fact, recent findings support this hypothesis by showing an
      association between neck injury and reduced amplitudes, speed and coordination of
      integrated jaw-neck movements. This study investigated the possible association
      between neck injury and disturbed eating behaviour. Fifty Whiplash-associated
      disorders (WAD) patients with pain and dysfunction in thejaw-face region and 50
      healthy age- and sex-matched controls without any history of neck injury
      participated in the study. All participants were assessed by a questionnaire,
      which contained 26 items about eating behaviour, jaw pain and dysfunction. For
      the WAD group there were significant differences in jaw pain and dysfunction and
      eating behaviour before and after the accident, but no significant differences
      between WAD before and healthy. The healthy and the WAD group before the accident
      reported no or few symptoms. The WAD patients after the accident reported pain
      and dysfunction during mouth opening, biting, chewing, swallowing and yawning and
      felt fatigue, stiffness and numbness in the jaw-face region. In addition, a
      majority also reported avoiding tough food and big pieces of food, and taking
      breaks during meals. Altogether, these observations suggest an association
      between neck injury and disturbed jaw function and therefore impaired eating
      behaviour. A clinical implication is that examination of jaw function should be
      recommended as part of the assessment and rehabilitation of WAD patients.

PMID- 19172919
TI  - Ectopic maxillary canines and root resorption of adjacent incisors. Does computed
      tomography (CT) influence decision-making by orthodontists?
AB  - The purpose of this investigation was to evaluate whether access to computed
      tomography (CT) influences orthodontists' decision-making about management of
      incisor root resorption due to ectopic maxillary canines. The study base
      comprised orthodontic specialists and active members of the Swedish Orthodontic
      Society: 182 orthodontists under 65 years of age, who had been registered
      specialists for at least one year and were providing specialist treatment for
      regular orthodontic patients. A questionnaire was sent out, comprising 8
      questions about management and decision-making in cases of ectopic maxillary
      canines with root resorption of adjacent incisors and 7 questions about practice
      profile. The orthodontists were asked whether they altered their treatment
      decisions when CT was available as a diagnostic tool. The response rate was high,
      86%. Sixty of the orthodontists had access to CT. Sixty-one percent of the 97
      orthodontists without access to CT stated that, in cases with space deficiency,
      they seldom or never considered extraction of a lateral incisor with suspected
      root resorption if the resorption was not discernible on intra-oral or panoramic
      radiographs. It was evident that even in cases of root resorption of lateral
      incisors due to ectopic canines,the orthodontists' management decisions were not
      particularly influenced by availability of CT diagnostic data. In the extraction
      cases 55% of the orthodontists considered extraction of the affected incisor
      first when root resorption was severe, i.e. involving the pulp and 37% when the
      resorption reached half way to the pulp. In cases without space deficiency 82%
      preferred to extract these resorbed lateral incisors not until the resorption
      reached the pulp.

PMID- 19172920
TI  - Cross-cultural adaptation and validation of the oral Iimpacts on daily
      performances (OIDP) in Swedish.
AB  - OBJECTIVES: The aim was to assess the validity and reliability of a Swedish
      version of the Oral impacts on Daily Performance (OIDP) index measuring oral
      health-related quality of life. MATERIAL AND METHODS: After translation and
      cultural adaptation, a 3-site sample of 204 adults (20-86 years) was interviewed
      using the OIDP. Moreover, the study included a self-administered questionnaire
      and a clinical examination. RESULTS: A total of 39.7% reported at least one oral
      impact on daily life. The most common performances affected were eating and
      cleaning teeth (both 20.6%). Oral effects on psychological performances caused
      the highest impacts. No gender or age differences were demonstrated with respect
      to having at least one impact. However, among those affected, women, old and
      young subjects scored higher than men and other ages, respectively, on the OIDP.
      The face and content validity were deemed good in pilot interviews with
      laypersons and dental professionals. The construct validity was confirmed, as the
      OIDP score was consistently associated with self-perceived oral health OR 2.13
      (95% CI 1.10-4.10) and other self-rated variables, e.g. satisfaction with oral
      health OR 2.43 (CI 1.34-4.41), also when accounting for age, gender and
      socioeconomic differences. Associations were estimated using logistic regression.
      Lacking 10 or more teeth was associated with a higher OIDP score, which supports
      the criterion validity of the instrument. In a test-retest analysis Cohen's kappa
      was 0.77. CONCLUSIONS: The Swedish version of the OIDP appears to be a valid and
      reliable measure for assessing oral impacts on daily performances.

PMID- 19172921
TI  - Relationships between psychosocial work environmental factors, personality,
      physical work demands and workload in a group of Swedish dentists.
AB  - The aim of the study was to investigate, in a group of 77 Swedish dentists (36
      males, 41 females) working in dental clinics, possible effects of psychosocial
      work environmental factors, personality traits, and social desirability
      tendencies on their reporting of their workload and of the physical demands
      placed on them. Participants were given questionnaires for assessing their
      workload, the physical and psychosocial demands of their job, their social
      support at work, and their control over their work situation, using a 10-cm
      visual analogue scale (V.A.S.). The Eysenck Personality Questionnaire (EPQ) was
      also given to assess neuroticism and extraversion and the Marlowe-Crown SD-scale
      to measure tendencies to answer questions in a socially desirable manner. As in
      two earlier studies of ours, very high assessments were made of workload,
      physical work demands and social support. Higher assessments of workload and of
      physical work demands were found in those assessing the psychosocial work demands
      placed on them to be higher. Those assessing the work load of their job as higher
      also considered themselves to have less control over their work situation and
      were less extraverted. Despite these dentists perceiving themselves as being
      faced with a stressful work situation involving a high workload, strong physical
      and psychosocial demands being placed on them and their having a low degree of
      control over their work situation, the high degree of social support they
      experienced may have made their work situation less stressful.

PMID- 19172922
TI  - Ageing and mortality in the UK--national statistician's annual article on the
      population.
AB  - The population of the UK is growing at the fastest rate since the 1960s,
      increasing on average by 0.5 per cent each year. The fastest growing age group is
      those aged 85 years and older, who now represent just over 2 per cent of the
      population, compared to just over 1 per cent in 1982. In 2007, continued increase
      in the population over state pension age meant for the first time this sub-group
      of the population exceeded the number aged under 16. Further improvements in
      survival mean both the continued growth of the older population and the likely
      continued ageing of the population as a whole. This is the second in a series of
      annual reports on the population of the UK, providing an overview of the latest
      statistics on the population, and focussing on a specific theme. This year's
      theme is the ageing population, with different topics to be covered in future
      years. The report highlights the work being taken forward as part of the National
      Statistics Centre for Demography (NSCD) work programme to understand the social
      and demographic impacts of an ageing society.

PMID- 19172923
TI  - Population turnover and churn: enhancing understanding of internal migration in
      Britain through measures of stability.
AB  - Net migration measures take account of the direction of migration flows, but our
      understanding of migration can be extended using population turnover and churn as
      measures of population stability. Turnover is a measure of the intensity of
      migration into and out of a district, whereas churn incorporates these flows and
      also includes the flows that take place within each district. Using districts of
      Britain and their type-based groupings, the highest levels of turnover and churn
      are found in London and some of the more dynamic urban areas, whereas the lowest
      levels are found in rural and previously industrial areas. Age has a significant
      effect on these measures with the population in their late teens and early
      twenties being the least stable and older populations being more stable.

PMID- 19172924
TI  - The National Population Projections Expert Advisory Group: results from a
      questionnaire about future trends in fertility, mortality and migration.
AB  - This article discusses the results of a questionnaire completed by the National
      Population Projections Expert Advisory Group in spring 2007. As well as asking
      for the experts' opinions on the most likely future levels of key fertility,
      mortality and migration indicators, views were collected about a wide range of
      factors that may have an influence on key demographic variables over the next 25
      years.

PMID- 19172925
TI  - Hepatitis B infection following deployment to Angola.
AB  - We describe the clinical illness and long-term follow up of two British personnel
      who acquired hepatitis B infection during a 3-month UN mission to Angola. Medical
      officers need to be familiar with this viral illness, which may present in
      military personnel after any exercise in or deployment to the tropics or
      subtropics.

PMID- 19172926
TI  - Audit of prescription of anti-malarial prophylaxis to patients admitted to Royal
      Centre for Defence Medicine (RCDM) following evacuation from Afghanistan.
AB  - INTRODUCTION: For most of the year Military personnel deployed to Afghanistan are
      required to take anti-malarial chemoprophylaxis (AMC). This audit aims to
      quantify how many personnel taking AMC in theatre have it continued at RCDM.
      METHOD: A database kept at RCDM was searched for details of all evacuated
      patients. Records of these patients were then searched to find out which had been
      admitted, how many had been taking AMC prior to admission and how many were
      prescribed it in hospital. RESULTS: During the study period 40 patients were
      evacuated to RCDM. 26 of these were admitted and had notes available and were
      therefore included in the study. 9 of these had been taking AMC prior to
      admission; of them, only 4 had been continued on AMC by the time they were
      admitted to RCDM. CONCLUSION: Insufficient numbers of patients taking AMC prior
      to admission have it continued as an inpatient. Awareness of this issue needs to
      be raised at all points of the medical evacuation chain.

PMID- 19172927
TI  - Update on Top Structures--Next Steps.

PMID- 19172928
TI  - Medical support to Navy Command headquarters.

PMID- 19172929
TI  - Surgical hand scrub: are alcohol gel based preparations a viable alternative on
      overseas operations?

PMID- 19172930
TI  - HCA nixes Pensacola deal. Baptist couldn't secure financing by deadline.

PMID- 19172931
TI  - HHS unveils six to eighty-six. Meantime, joint commission revises its standards.

PMID- 19172932
TI  - New year's stress. ACHE survey shows finances lead execs' concerns.

PMID- 19172934
TI  - Quality push continues.

PMID- 19172933
TI  - Battling the clones. CHW wants to avoid genetically altered foods.

PMID- 19172935
TI  - Swiping savings. MGMA renews push for machine-readable ID cards.

PMID- 19172936
TI  - Belt-tightening time. Recession-proof? Doc investors fear not.

PMID- 19172937
TI  - Haunted by HIV's origins.

PMID- 19172938
TI  - Three-star snacks aisle five.

PMID- 19172939
TI  - Sorry, but I can't help you.

PMID- 19172940
TI  - Time for a debate on folate? Too much of a good thing could turn out to be bad.

PMID- 19172941
TI  - Sex ed for seniors: you still need those condoms. Sexually transmitted diseases
      stalk older singles, too.

PMID- 19172943
TI  - The passions behind the pill. Helping women in poverty is what drove the
      development of the oral contraceptive.

PMID- 19172942
TI  - A new knee built for women only. The pitch: the female body needs its own design.

PMID- 19172945
TI  - Fear and allergies in the lunchroom.

PMID- 19172944
TI  - Lessons from a bug. A pandemic filled beds but offered important insights.

PMID- 19172946
TI  - Knocking yourself up.

PMID- 19172947
TI  - The ghosts we think we see.

PMID- 19172948
TI  - Unlucky charms at lunch.

PMID- 19172949
TI  - What's chemo, mommy?

PMID- 19172950
TI  - The case for chutes and ladders.

PMID- 19172951
TI  - Your child was out of line.

PMID- 19172953
TI  - An Rx for women. CVS Caremark aims to be a one-stop shop for stressed customers.

PMID- 19172952
TI  - An inconvenient price.

PMID- 19172954
TI  - Taking care of your parents. 15 ways to safeguard their health, wealth, and
      happiness.

PMID- 19172955
TI  - The need for a long-range plan. If you expect to care for your parents, think and
      act like a CEO.

PMID- 19172956
TI  - Confronting sadness in seniors. Often undiagnosed in the elderly, depression has
      telltale signs.

PMID- 19172957
TI  - Get moving, seniors--age is no excuse. New exercise guidelines call for several
      workouts a week.

PMID- 19172958
TI  - The power of the aging mind.

PMID- 19172959
TI  - Market structure elements: the case of California nursing homes.
AB  - This article empirically examines how various elements of market structure affect
      the pricing behavior and profitability of individual nursing homes in California.
      Market structure elements include seller concentration, the concentration of
      nursing homes organized on a nonprofit basis, and concentration of nursing homes
      organized on an independent basis in the market area. It is hypothesized that the
      latter two variables affect the nature of competition in the market area. Using
      data for year 2000, the empirical results suggest that both the private payer
      price and Lerner index are higher in nursing home market areas with increased
      seller concentration and concentration of secular, not-for-profit nursing homes.
      Neither price nor profitability is influenced by the market concentration of
      independent nursing homes, however. All in all, the study suggests that the
      typical California nursing home possesses some degree of market power, even in
      the absence of a state certificate of need law.

PMID- 19172960
TI  - Pay-for-performance as a method to establish the business case for quality.
AB  - One of the major reasons providers give for not implementing promising quality
      enhancing interventions (QEI) is that no "business case" for quality has been
      made. This article clarifies the concepts of the business case for quality and
      the related economic case for quality and identifies the perspectives of the
      various actors in health care financing, production, and consumption decisions. A
      methodology to evaluate the business case for quality from the perspective of
      payers and providers is presented. The article then uses implemented QEIs to show
      how a pay-for-performance (P4P) program can alter the business cases for payers
      and providers. Specifically, the P4P programs described in this article allow a
      provider to implement a QEI with the financial alignment of the payer in order to
      achieve financial and non-financial benefits. In some cases, providers and payers
      may be able to establish P4P programs providing net benefits for both parties.

PMID- 19172961
TI  - The financing of hospital-based emergency departments.
AB  - This article describes the principal channels of reimbursement for hospital-based
      emergency departments, and considers the impact of these funding streams on the
      organization and delivery of emergency care. We describe the services offered in
      the emergency department setting, reimbursement methodologies, factors affecting
      reimbursement, and the costs of hospital-based emergency services. We examine
      hospital financing and the contribution of the emergency department to the
      hospital's patient and service mixes and to its financial bottom line. We
      identify perverse payment incentives in terms of quality, efficiency, and broad
      system goals, and consider how payment incentives can be used to improve patient
      safety and quality of care.

PMID- 19172962
TI  - What we know and do not know about tiered provider networks.
AB  - In response to continuing concerns about escalating health care costs and poor
      quality care, many health plans have adopted a strategy called "tiered provider
      networks." With TPNs, plans provide financial incentives for members to utilize
      hospitals, primary care physicians, and/or specialist physicians identified as
      performing especially well in terms of cost-efficient and/or high-quality care.
      The strategy is relatively new, and little is known about TPN structure,
      implementation, or operation. In this article, we present findings about tiered
      provider networks developed from a national survey of health plans and from
      interviews with health plan executives, their employer clients, and providers in
      their networks.

PMID- 19172963
TI  - Chronic disease prevalence and burden in elderly men: an analysis of Medicare
      medical claims data.
AB  - Because of the lack of information on men's health issues, and the substantial
      economic and morbidity impact of chronic diseases in this population, the current
      study describes the prevalence and burden of the top ten chronic diseases
      diagnosed in males age 65 and older. This study will provide insight to providers
      and benefit administrators seeking to develop educational and therapy management
      programs to reduce acute and long-term complications associated with the most
      prevalent chronic medical conditions.

PMID- 19172964
TI  - The effects of location and race on the performance of cardiac procedures.
AB  - This study assessed the impact of patient and facility characteristics on patient
      outcomes for coronary artery disease. The sample data studied and analyzed (i.e.,
      hospital financial and administrative data) were from patients discharged in
      2004, from hospitals in Florida with principal diagnoses codes indicating
      diseases of the circulatory system. Patient outcomes were measured as principal
      procedure codes for patients who received coronary arteriography, percutaneous
      transluminal coronary angioplasty, and coronary artery bypass graft surgeries.
      Chi-square analysis indicated that both patient location (chi 2 = 225.9038, p <
      .0001) and race (chi 2 = 312.1335, p < .0001) were associated with the receipt of
      cardiovascular procedures.

PMID- 19172965
TI  - Outsourcing and its implications for hospital organizations in Turkey.
AB  - To thrive in this era of global competition, all organizations must explore new
      managerial approaches to get an edge in the marketplace. One increasingly
      appealing approach is outsourcing. Hospitals are particularly fertile
      environments for outsourcing, given their role as providers of a broad and
      complex array of services, many of which may be bought from other institutions.
      The purpose of this study is to determine the types of services that hospitals in
      Turkey buy from other organizations. The study sample included 14 university
      hospitals, 20 Ministry of Health Hospitals, 15 Social Insurance Organization
      Hospitals and 31 private hospitals in Istanbul, Ankara, Izmir, Antalya, and
      Eskisehir, which are the biggest cities in Turkey. The following services were
      found to be outsourced: hospital management information systems (83.8%), cleaning
      services (81.3%), maintenance services (72.5%), leased medical devices (75.0%),
      food services (60.0%), patient direction services (63.8%), magnetic imaging
      services (60.0%), other imaging services (48.8%), laboratory services (42.5%),
      security services (38.8%), laundry services (36.3%), patient transportation
      services (33.8%), accounting services (26.3%), ambulance services (22.5%),
      patient satisfaction measurement services (13.8%), consultancy services (12.5%),
      and financial and investment services (9.5%). Private hospitals bought more
      services than public facilities did. The sampled hospitals chose to outsource
      services in order to decrease costs (78.8%), increase the quality of services
      rendered (65.5%), increase flexibility and share risk (36.6%), and increase
      profits (11.2%). The results of this study suggest that outsourcing, when applied
      judiciously through cost and risk analysis, is a cost-effective approach that can
      be used by most hospitals.

PMID- 19172966
TI  - Health status, risk factors and unmet needs of diverse populations.

PMID- 19172967
TI  - Korean American mother and daughter communication on women's health topics.
AB  - The purpose of this study was to explore communication patterns about health
      behaviors and lifestyles between Korean mothers and daughters living in the
      United States. Demographic and general health information was also collected.
      Semi-structured interviews were conducted with nine Korean mother and daughter
      dyads. Korean mothers talked with their daughters about healthy diets and
      exercise but relied on daughters' schools to provide much of their
      daughters'health education information related to growth and developmental
      changes and women's health issues such as screening and HIV prevention practice.
      Intervention models to enhance mother/daughter health communication and to
      improve mothers' self care need to be investigated.

PMID- 19172968
TI  - The caregiving experience among Hispanic caregivers of dementia patients.
AB  - This research reviewed studies that investigated factors influencing the
      caregiving experience among informal Hispanic caregivers of dementia patients.
      This review identified 24 journal articles published between 1985 and 2003.
      Variables studied were depression and social support. In addition, methodological
      issues were detected such as sampling bias and multiple measurements. This review
      concluded that there is a need for an extensive, in depth research of the
      caregiving experience among Hispanics and further research needs are discussed.

PMID- 19172969
TI  - Mental health symptoms in Iraqi refugees: posttraumatic stress disorder, anxiety,
      and depression.
AB  - Refugees suffer from a higher rate of mental health symptoms than the general
      population since they have experienced extreme suffering and the accumulated
      effects of trauma. Because of the diversity of regions from which refugees
      originate, there is a need to understand some of the unique experiences that are
      specific to each sub-groups of immigrants. The purpose of the present study was
      to explore mental health symptoms in Iraqi refugee clients who immigrated to the
      United States after the Gulf War of the early 1990's. As part of a larger study,
      116 adult Iraqi immigrants to the United States (46 male, 70 females) who were
      seeking mental health services completed measures of anxiety, depression, and
      posttraumatic stress disorder. As expected, the majority of refugees reported
      intense anxiety and depression, and many met the DSM IV criteria for
      posttraumatic stress disorder. Like refugees from other countries-of-origin,
      Iraqi refugees are in need of culturally sensitive assessment and mental health
      treatment. The results are discussed in light of the treatment needs of Iraqi
      refugee clients, their resilience and motivation for a better life, and the ways
      that health professionals can assist in optimizing their adjustment.

PMID- 19172970
TI  - Migrant Latinas and brothel sex work in Belize: sexual agency and sexual risk.
AB  - Sexual risk variability among brothel-based sex workers has been shown to be
      influenced by fear of HIV transmission, and by culture-bound gender norms as well
      as economic need, yet the effect of sexual agency on impoverished Latina sex
      workers' risk behavior with their clients remains poorly characterized. We
      investigated perceived health beliefs regarding susceptibility to/severity of
      HIV/AIDS, and sexual agency regarding barriers to condom use, benefits of
      unprotected sex, and risk-reduction behavior with clients among a sample of 33
      brothel workers in Belize. Although 77% of participants felt at risk for HIV,
      only 30% always use condoms and 43% did not refuse unprotected sex with clients.
      Participants' narrative explanations for unprotected sex emphasized that
      clients'preferences often overrode brothel workers fear of HIV, and that the
      health benefits of using condoms with clients were often weighed against the
      social benefits of unprotected sex. Implications for brothel-based condom
      promotion programs and further research are discussed.

PMID- 19172971
TI  - Developing an international learning experience in The Gambia, West Africa: the
      rewards and challenges of a complex partnership.
AB  - An international educational program that engages students in healthcare in
      another culture is a wonderful way to immerse students in diversity issues.
      However, developing these types of international programs are challenging for
      many reasons. It takes a great deal of time, financial resources, and ongoing
      commitment from all involved. Even with the known benefits of developing
      international educational partnerships many nursing programs lack the personnel
      and/or financial resources to develop and/or to sustain these programs overtime.
      By partnering with other universities and local hospitals extra financial and
      personnel resources become available to develop and help sustain these
      international educational programs.

PMID- 19172972
TI  - Learning disabilities in the community college and the role of disability
      services departments.
AB  - The community college offers educational opportunities to a diverse population of
      students. Many of the students attending the community college are considered non
      traditional, and have numerous factors not faced by traditional-age students that
      can affect retention in this population. Learning disabled (LD) students attend
      the community college at a higher rate than other higher education institutions
      (Barnett, 1996; Bigaj, 1995; & Henderson, 1992). The American Association of
      Community Colleges (AACC) reported that LDs now constitute the largest single
      category of disability served by disability service offices in the community
      colleges (Barnett, 1992). Accommodations are set up by the Disability Support
      Services Departments, and it is the Disability Services offered by the college
      that can be the deciding factor for the student regarding the choice of
      institution (Cocchi, 1997). A trend for the future involves many students who
      attend the community college self-identifying as being learning disabled and
      requesting accommodation. Faculty, staff, and administrators in the community
      college will need to be very familiar with legislation that impacts the rights
      and availability of services for LD students.

PMID- 19172973
TI  - Charting the 7 c's of cultural change affecting foreign nurses: competency,
      communication, consistency, cooperation, customs, conformity and courage.
AB  - Eighty-two percent of practicing RNs are located in metropolitan areas in which
      the predominant employment setting is the hospital according to the National
      Sample Survey of Registered Nurses (Services, 2000). However, despite current
      trends toward moderate increased enrollment in nursing schools, a 2001American
      Hospital Survey (AHA) among 715 member hospitals revealed that 126,000 registered
      nurse positions across America remain unfilled. As a result, hospitals have
      adopted creative solutions to ease the nursing shortage. One creative solution is
      to import foreign nurses. According to the Commission on Graduates of Foreign
      Nursing Schools (CGFNS) many come from the Philippines, are single, female and
      between 23-27 years of age. The foreign nurse will encounter many barriers and
      practice problems no matter his/her level of skill. This article explores seven
      areas of clinical competency that nurses from the Philippines will encounter and
      must surmount as well as some of the implications for nursing practice that
      veteran and newly graduated nurses might want to be aware of when working with
      foreign nurses.

PMID- 19172975
TI  - Minority nurses' experiences on the job.
AB  - While a number of studies have explored questions regarding career path and job
      satisfaction among nurses, the data rarely are examined for distinct racial and
      ethnic groups. Furthermore, we have not found any study that has explored the
      relationship between ethnicity and factors that foster job satisfaction among
      nurses. The purpose of this study is to describe the work environment, job
      advancement, and promotion experiences of registered nurses in California who
      self-identify an ethnic affiliation. We tried to determine if minority nurses
      faced more and/or different barriers to career advancement than white nurses.
      Overall, we found that minority nurses have positive views of their opportunities
      and workplaces. They are more likely than white nurses in the sample to agree
      that they have opportunities to learn new skills at work, to think their job
      duties match their skills, and to believe they have opportunities to advance at
      their workplace.

PMID- 19172974
TI  - Beyond self-assessment--assessing organizational cultural responsiveness.
AB  - While there is growing recognition of the need for health care organizations to
      provide culturally responsive care, appropriate strategies for assessing
      organizational responsiveness have not been determined. A document review
      assessment instrument was designed to assess best practice within eight domains,
      and along seven dimensions of organizational approach to diversity. Results
      obtained from the pilot of the instrument were congruent with data collected from
      key informant interviews, a focus group, observational methods and organizational
      feedback session; however, they were not consistent with self-assessment results
      at the same site. A larger pilot is required to determine generalizability of
      results.

PMID- 19172976
TI  - The Patient Health Questionnaire (PHQ-9K) to screen for depressive disorders
      among immigrant Korean American elderly.
AB  - Korean American (KA) elderly by utilizing the translated Patient Health
      Questionnaire (PHQ-9K). Based on the literature related to cultural expression of
      depression among KAs, the PHQ-9 was selected, translated into Korean (PHQ-9K),
      and utilized. Data were collected at an Asian Senior Center and analyzed
      according to the diagnostic assessment and severity of depression criteria.
      Findings indicated that among the participants, 15 % definitely require treatment
      for depression and 3.4 % had suicide ideation daily during the two-week period
      preceding data collection. Two hypotheses were supported: A high prevalence of
      depression exists among KA elderly and the PHQ-9K may be a culturally appropriate
      instrument to detect depression in KA elderly. KA Senior Centers can be ideal
      places to screen for depression in KA elderly who are unable to access current
      health care systems when they experience depressive disorders.

PMID- 19172977
TI  - Engaging community in the quality of hypertension care project with Hmong
      Americans.
AB  - This paper describes the collaborative endeavors between researchers and the
      Hmong community to develop and test a quality of hypertension care survey
      instrument. In-depth interviews with community leaders and hypertensive patients
      enhanced the understanding of quality of care from Hmong socio-cultural
      perspectives. Knowledge gained from the Hmong community was integrated into the
      research process. The collaborative process led to generating a culturally
      sensitive survey instrument, overcoming cultural barriers for recruitment of
      survey participants, and facilitating community involvement in all aspects of
      research implementation. Applying community-sensitive research methods ensured
      the success of the project.

PMID- 19172978
TI  - Transcultural nursing: its importance in nursing practice.
AB  - Transcultural nursing is an essential aspect of healthcare today. The ever
      increasing multicultural population in the United States poses a significant
      challenge to nurses providing individualized and holistic care to their patients.
      This requires nurses to recognize and appreciate cultural differences in
      healthcare values, beliefs, and customs. Nurses must acquire the necessary
      knowledge and skills in cultural competency. Culturally competent nursing care
      helps ensure patient satisfaction and positive outcomes. This article discusses
      changes that are important to transcultural nursing. It identifies factors that
      define transcultural nursing and analyzes methods to promote culturally competent
      nursing care. The need for transcultural nursing will continue to be an important
      aspect in healthcare. Additional nursing research is needed to promote
      transcultural nursing.

PMID- 19172979
TI  - Integrating the core professional values of nursing: a profession, not just a
      career.
AB  - To meet the predicted deficit of more than 1 million nurses by 2020, traditional
      nursing recruitment must target previously un-recruited populations, as well as a
      culturally diversified workforce to include variations in age, ethnicity, gender,
      life style, national origin, and sexual orientations. As diversity increases,
      differences must be bridged to acculturate new nurses to recognize and identify
      with a shared nursing ideology and culture. The core professional nursing values
      (CPNVs) impart a common foundation that unites students and nurses in a
      meaningful, collective culture. Baccalaureate nursing programs actively
      promulgate these professional nursing values, however, methods to incorporate
      them into curricula are often absent from the literature. Following an
      intervention integrating the CPNVs into academic education, students affirmed the
      usefulness of this approach describing that the integration of the core values
      created a shared culture of professional nursing and deepened their commitment to
      the profession. Incorporating the CPNVs provided a promising approach that
      bridged the cultural chasm of a highly diverse student population and the
      profession of nursing by creating a shared professional culture across the myriad
      differences.

PMID- 19172980
TI  - Hispanics' experiences in the health system prior to hospice admission.
AB  - National data document that Hispanics are under-represented in hospice. Policy
      makers often attribute the under-representation to Hispanics' cultural values and
      preferences, however, another reason may be healthcare system barriers
      encountered by Hispanics. We explored Hispanics' versus Whites' experiences in
      the healthcare system prior to hospice admission to help account for Hispanics
      under-representation in hospice. The conceptual model was the Agency for
      Healthcare Research and Quality Model on Healthcare Access. Whites' experiences
      were used as benchmarks to identify healthcare disparities for Hispanics. In four
      hospice agencies, Hispanic (n = 60) and White (n = 60) Medicare patients were
      interviewed. The results showed that prior to hospice admission, Hispanics had
      less access to health services known to be associated with hospice access.

PMID- 19172981
TI  - The use of prayer by Hispanic migrant farmworkers with type 2 diabetes.
AB  - Praying for issues related to health can be a very important aspect in peoples'
      lives. Since research on this practice is limited, a qualitative study was
      conducted that explored the use of prayer in Hispanic migrant farmworkers
      diagnosed with type 2 diabetes. Eighteen farmworkers were interviewed and asked
      two specific questions with multiple probes to elicit information regarding their
      religious practices and prayer. Responses regarding religious practices were
      extremely limited whereas the farmworkers expounded on the question relating to
      prayer. Three main themes emerged: 1) Farmworkers used prayer in their daily
      lives; 2) Farmworkers prayed for themselves and their family; and 3) Farmworkers
      recited prayers specifically for their diabetes.

PMID- 19172982
TI  - Health disparities among Latina/o adolescents in urban and rural schools:
      educators' perspectives.
AB  - This qualitative pilot study examined health disparities among rural and urban
      Latina/o adolescents from the perspective of middle and high school
      administrators, counselors, nurses, and teachers. Participants were asked to
      describe Latina/o health disparities in their schools, reasons attributed to
      health disparities, and school-based interventions for addressing health
      disparities. Focus group participants reported that common health disparities for
      Latina/o youth in rural and urban settings include poor vision care and high
      teenage pregnancy rates. However, participants reported differences in physical
      health and mental health disparities, as well as differences in social-cultural
      economic contributors to disparities and school-based interventions.

PMID- 19172983
TI  - Ageless health needs assessment on the U.S.-Mexico border: Ciudad Juarez.
AB  - OBJECTIVES: The Ageless Health Needs Assessment Study examined the self-reported
      health of the 60 and older population along the U.S.-Mexico border. METHODS: A
      health survey was administered in Ciudad Juarez, Chihuahua, Mexico to 507 Mexican
      descendents by telephone (n = 296) and in-person (n = 211). The health survey
      examined measures of physical and psychosocial health. RESULTS: All participants
      were aged 60 and older and born in Mexico. Most reported achieving an elementary
      school education or less and many lived in poverty. Results from a MANCOVA showed
      significant differences between groups: men, individuals with higher education,
      and sufficient amounts of physical activity reported better health scores
      compared to women, individuals with lower education, and insufficient physical
      activity. CONCLUSIONS: These findings suggest that higher levels of education and
      physical activity may be associated with better health outcomes among elderly
      Mexicans dwelling on the border.

PMID- 19172984
TI  - How New Mexico licensed registered nurses gained cultural self-efficacy and their
      stories.
AB  - The cultural self-efficacy of licensed registered nurses in New Mexico has been
      reported by this author in two previous articles (Hagman, 2004 & 2006). The
      Cultural Self-Efficacy Scale (CSES) developed by Bernal and Froman (1987) was
      used to quantify New Mexico RN's knowledge of cultural concepts, skills and life
      patterns of five ethnic groups (White-non Hispanic, Hispanic, African American,
      Asian American and Native American). Methods used included quantitative survey
      results and written responses to two open-ended questions yielding both
      quantitative and qualitative data. This article provides details of the
      qualitative data which revealed how the RNs in that study gained their reported
      level of self-efficacy and the stories they shared. Data analysis revealed four
      major themes; experience, education, travel, and military service. Examples are
      provided for each theme. Participants also shared cultural stories/anecdotes

PMID- 19172985
TI  - Health practices and expectations of Brazilians in the United States.
AB  - This ethnographic examination of Brazilian immigrant perspectives regarding
      healthcare in the U.S. included participant observation and interviews with 42
      Brazilian transnationals. Data were analyzed using Agar's approach. Findings show
      that Brazilians accessed allopathic care only as a last resort after self
      treatment strategies failed, that they tended to feel that diagnostic testing,
      referrals, and symptom-relieving prescriptions were imperative to good care, and
      that they expected more personal warmth, continuity of care, and more
      affectionate verbal and nonverbal cues than their U.S. clinicians provided.
      Recommendations to improve quality of healthcare to Brazilian transnationals in
      the USA are discussed.

PMID- 19172986
TI  - The double burden of malnutrition. Case studies from six developing countries.

PMID- 19172987
TI  - Chromosome 13q13-q14 locus overlaps mood and psychotic disorders: the relevance
      for redefining phenotype.
AB  - The nosology of major psychoses is challenged by the findings that schizophrenia
      (SZ) and bipolar disorder (BP) share several neurobiological, neuropsychological
      and clinical phenotypic characteristics. Moreover, several vulnerability loci or
      genes may be common to the two DSM disorders. We previously reported, in a sample
      of 21 kindreds (sample 1), a genome-wide suggestive linkage in 13q13-q14 with a
      common locus (CL) phenotype that crossed the diagnostic boundaries by combining
      SZ, BP and schizoaffective disorders. Our objectives were to test phenotype
      specificity in a separate sample (sample 2) of 27 kindreds from Eastern Quebec
      and to also analyze the combined sample of 48 kindreds (1274 family members). We
      performed nonparametric and parametric analyses and tested as phenotypes: SZ
      alone, BP alone, and a CL phenotype. We replicated in sample 2 our initial
      finding with CL with a maximum NPL(pair) score of 3.36 at D13S1272 (44 Mb), only
      2.1 Mb telomeric to our previous maximum result. In the combined sample, the peak
      with CL was at marker D13S1297 (42.1 Mb) with a NPL(pair) score reaching 5.21,
      exceeding that obtained in each sample and indicating consistency across the two
      samples. Our data suggest a susceptibility locus in 13q13-q14 that is shared by
      schizophrenia and mood disorder. That locus would be additional to another well
      documented and more distal 13q locus where the G72/G30 gene is mapped.

PMID- 19172988
TI  - The complex interaction between APOE promoter and AD: an Italian case-control
      study.
AB  - The single nucleotide polymorphisms (SNPs) rs449647, rs769446 and rs405509 in the
      promoter region of the APOE gene have been variously suggested to be epsilon 4
      independent risk factors for Alzheimer's disease (AD). A previous Italian study
      found that the rs449647 was significantly associated with late-onset AD. The aim
      of this study was to verify whether these APOE promoter SNPs are genetic risk
      factors for AD and to investigate their interaction with the common APOE
      polymorphism. A total of 169 clinically diagnosed AD patients and 99 cognitively
      intact age-matched controls were included in the study. Significant associations
      with AD independent from sex, age and APOE/epsilon 4 status were found for
      rs449647 A/A and rs405509 G/G genotypes (positive), and rs449647 A/T and rs405509
      T/T genotypes (negative). Haplotype frequency estimation at the APOE locus showed
      significant associations for the ATG4, ATT4 and ACG3 (positive) and ATT2, ATT3
      and TCG3 (negative) haplotypes. Therefore this study confirms the role of the
      rs449647 A/A genotype as risk factor for AD in Italy and suggests that promoter
      genotypes and APOE haplotypes might have a complex function in AD-associated
      genetic risk factors.

PMID- 19172989
TI  - Increased expression of the Hutchinson-Gilford progeria syndrome truncated lamin
      A transcript during cell aging.
AB  - Most cases of the segmental progeroid syndrome, Hutchinson-Gilford progeria
      syndrome (HGPS), are caused by a de novo dominant mutation within a single codon
      of the LMNA gene. This mutation leads to the increased usage of an internal
      splice site that generates an alternative lamin A transcript with an internal
      deletion of 150 nucleotides, called lamin A Delta 150. The LMNA gene encodes two
      major proteins of the inner nuclear lamina, lamins A and C, but not much is known
      about their expression levels. Determination of the overall expression levels of
      the LMNA gene transcripts is an important step to further the understanding of
      the HGPS. In this study, we have performed absolute quantification of the lamins
      A, C and A Delta 150 transcripts in primary dermal fibroblasts from HGPS patients
      and unaffected age-matched and parent controls. We show that the lamin A Delta
      150 transcript is present in unaffected controls but its expression is >160-fold
      lower than that in samples from HGPS patients. Analysis of transcript expression
      during in vitro aging shows that although the levels of lamin A and lamin C
      transcripts remain unchanged, the lamin A Delta 150 transcript increases in late
      passage cells from HGPS patients and parental controls. This study provides a new
      method for LMNA transcript analysis and insights into the expression of the LMNA
      gene in HGPS and normal cells.

PMID- 19172990
TI  - Genetic analysis of autosomal recessive osteopetrosis in Chuvashiya: the unique
      splice site mutation in TCIRG1 gene spread by the founder effect.
AB  - The rare malignant disorder autosomal recessive osteopetrosis (OPTB) is one of
      the most prevalent autosomal recessive diseases in the Chuvash Republic of
      Russia. The purpose of this study was to determine the underlying molecular cause
      of osteopetrosis in Chuvashiya and to reveal the factors causing the unusual high
      frequency of the disease in this region. Having assumed a founder effect, we
      performed linkage disequilibrium (LD) mapping of the OPTB locus at the TCIRG1
      region and found a unique splice site mutation c.807+5G>A in all Chuvashian OPTB
      patients studied. We then analyzed the mutational change in mRNA and detected an
      intron insertion within the mutant transcript, resulting in a frameshift and
      premature stop-codon formation (p.Leu271AspfsX231). A decreased expression of the
      mutant transcript was also detected, which may have been the result of nonsense
      mediated decay. Real-time qPCR and MLPA melting curve analysis-based systems were
      designed and used for c.807+5G>A mutation screening. In addition to analyzing the
      gene frequency in Chuvashiya, we also estimated three other populations in the
      Volga-Ural region (Mari, Udmurt and Bashkir). We found a 1.68% prevalence in
      Chuvashiya (calculated disease frequency, 1/3500 newborns) and a 0.84% in the
      Mari population (1/14 000 newborns). The haplotype analysis revealed that all
      OPTB cases in Chuvashians and Marians originated from a single mutational event
      and the age of the mutation in Chuvashians was estimated to be approximately 890
      years.

PMID- 19172992
TI  - An international external quality assessment for molecular diagnosis of
      hereditary recurrent fevers: a 3-year scheme demonstrates the need for
      improvement.
AB  - Hereditary recurrent fevers (HRF) are rare diseases caused by molecular defects
      in genes involved in the regulation of innate immunity. Sixty-seven international
      laboratories participated in an external quality assessment (EQA) scheme, which
      was developed to appraise the accuracy of genetic testing. Reports were evaluated
      for the 12 items recommended by the OECD (Organisation for Economic Co-Operation
      and Development) guidelines for molecular diagnostics. The best documented items
      were the name of the gene, the biologist, or the patient, whereas information on
      the test and screening limits, and clinical interpretation of the disease
      inheritance were scarcely provided. The mutation nomenclature was incomplete in
      about 70% of the cases. In the first 2 years of EQA, we identified almost 30%
      genotyping error rate, which decreased markedly in the last year. The combined
      performance on the basis of the correct identification of all genotypes by a
      given laboratory in all the 3 years was only 40%, showing a critical need for
      improvement.

PMID- 19172991
TI  - Centrotemporal sharp wave EEG trait in rolandic epilepsy maps to Elongator
      Protein Complex 4 (ELP4).
AB  - Rolandic epilepsy (RE) is the most common human epilepsy, affecting children
      between 3 and 12 years of age, boys more often than girls (3:2). Focal sharp
      waves in the centrotemporal area define the electroencephalographic (EEG) trait
      for the syndrome, are a feature of several related childhood epilepsies and are
      frequently observed in common developmental disorders (eg, speech dyspraxia,
      attention deficit hyperactivity disorder and developmental coordination
      disorder). Here we report the first genome-wide linkage scan in RE for the EEG
      trait, centrotemporal sharp waves (CTS), with genome-wide linkage of CTS to 11p13
      (HLOD 4.30). Pure likelihood statistical analysis refined our linkage peak by
      fine mapping CTS to variants in Elongator Protein Complex 4 (ELP4) in two
      independent data sets; the strongest evidence was with rs986527 in intron 9 of
      ELP4, providing a likelihood ratio of 629:1 (P=0.0002) in favor of an
      association. Resequencing of ELP4 coding, flanking and promoter regions revealed
      no significant exonic polymorphisms. This is the first report of a gene
      implicated in a common focal epilepsy and the first human disease association of
      ELP4. ELP4 is a component of the Elongator complex, involved in transcription and
      tRNA modification. Elongator depletion results in the brain-specific
      downregulation of genes implicated in cell motility and migration. We hypothesize
      that a non-coding mutation in ELP4 impairs brain-specific Elongator-mediated
      interaction of genes implicated in brain development, resulting in susceptibility
      to seizures and neurodevelopmental disorders.

PMID- 19172993
TI  - Characterization of a t(5;8)(q31;q21) translocation in a patient with mental
      retardation and congenital heart disease: implications for involvement of RUNX1T1
      in human brain and heart development.
AB  - The chromosome break points of the t(8;21)(q21.3;q22.12) translocation associated
      with acute myeloid leukemia disrupt the RUNX1 gene (also known as AML1) and the
      RUNX1T1 gene (also known as CBFA2T3, MTG8 and ETO) and generate a RUNX1-RUNX1T1
      fusion protein. Molecular characterization of the translocation break points in a
      t(5;8)(q32;q21.3) patient with mild-to-moderate mental retardation and congenital
      heart disease revealed that one of the break points was within the RUNX1T1 gene.
      Analysis of RUNX1T1 expression in human embryonic and fetal tissues suggests a
      role of RUNX1T1 in brain and heart development and support the notion that
      disruption of the RUNX1T1 gene is associated with the patient's phenotype.

PMID- 19172994
TI  - Dystrophia myotonia: why focus on foci?
AB  - Dystrophia myotonia type 1 (DM1; Steinert's disease; myotonic dystrophy) is an
      autosomal dominant disorder due to a large CTG expansion in the 3'-untranslated
      region (UTR) of the DM protein kinase (DMPK) gene. Transcription of this gene
      yields a long CUGn-containing mutant (mut) RNA, in which clinical disease is
      associated with repeats of n=100-5000. Phenomenologically, the expression of mut
      RNA is correlated with the morphologic observation of ribonucleoprotein
      precipitates ('foci') in the nuclei of DMPK-expressing cells. The prevailing view
      is that the identification of proteins in these foci is the sine qua non of
      protein-mut RNA interactions. In this viewpoint, I contend that this is an
      unwarranted inference that falls short in explaining published data. A new model
      of mut RNA-protein interactions is proposed with distinct binding properties for
      soluble and insoluble (focus) mut RNA that accommodate these data without
      exclusions.

PMID- 19172995
TI  - Evidence of combat in triceratops.
AB  - BACKGROUND: The horns and frill of Triceratops and other ceratopsids (horned
      dinosaurs) are interpreted variously as display structures or as weapons against
      conspecifics and predators. Lesions (in the form of periosteal reactive bone,
      healing fractures, and alleged punctures) on Triceratops skulls have been used as
      anecdotal support of intraspecific combat similar to that in modern horned and
      antlered animals. If ceratopsids with different cranial morphologies used their
      horns in such combat, this should be reflected in the rates of lesion occurrence
      across the skull. METHODOLOGY/PRINCIPAL FINDINGS: We used a G-test of
      independence to compare incidence rates of lesions in Triceratops (which
      possesses two large brow horns and a smaller nasal horn) and the related
      ceratopsid Centrosaurus (with a large nasal horn and small brow horns), for the
      nasal, jugal, squamosal, and parietal bones of the skull. The two taxa differ
      significantly in the occurrence of lesions on the squamosal bone of the frill (P
      = 0.002), but not in other cranial bones (P > 0.20). CONCLUSIONS/SIGNIFICANCE:
      This pattern is consistent with Triceratops using its horns in combat and the
      frill being adapted as a protective structure for this taxon. Lower pathology
      rates in Centrosaurus may indicate visual rather than physical use of cranial
      ornamentation in this genus, or a form of combat focused on the body rather than
      the head.

PMID- 19172996
TI  - Whi5 regulation by site specific CDK-phosphorylation in Saccharomyces cerevisiae.
AB  - The Whi5 transcriptional repressor is a negative regulator of G1 cell cycle
      progression in Saccharomyces cerevisiae and is functionally equivalent to the
      Retinoblastoma (Rb) tumor suppressor protein in mammals. In early G1, Whi5 binds
      to and inhibits SBF (Swi4/Swi6) transcriptional complexes. At Start, Cln:Cdc28
      kinases phosphorylate and inactivate Whi5, causing its dissociation from SBF
      promoters and nuclear export, allowing activation of SBF transcription and entry
      into late G1. In an analysis of Whi5 phosphorylation, we found that 10 of the 12
      putative CDK phosphorylation sites on Whi5 were occupied in vivo in
      asynchronously growing cells. In addition, we identified 6 non-CDK Whi5
      phosphorylation sites. Whi5 CDK and non-CDK phosphorylation mutants were
      functional and able to rescue the small cell size of whi5Delta cells. However,
      the Whi5 CDK mutant with all 12 putative CDK sites changed to alanine causes a
      dramatic cell cycle phenotype when expressed with a Swi6 CDK phosphorylation
      mutant. Mutational analysis of Whi5 determined that only four C-terminal CDK
      sites were necessary and sufficient for Whi5 inactivation when Swi6 CDK sites
      were also mutated. Although these four Whi5 CDK sites do not wholly determine
      Whi5 nuclear export, they do impact regulation of cell size. Taken together,
      these observations begin to dissect the regulatory role of specific
      phosphorylation sites on Whi5.

PMID- 19172997
TI  - CAMKII activation is not required for maintenance of learning-induced enhancement
      of neuronal excitability.
AB  - Pyramidal neurons in the piriform cortex from olfactory-discrimination trained
      rats show enhanced intrinsic neuronal excitability that lasts for several days
      after learning. Such enhanced intrinsic excitability is mediated by long-term
      reduction in the post-burst after-hyperpolarization (AHP) which is generated by
      repetitive spike firing. AHP reduction is due to decreased conductance of a
      calcium-dependent potassium current, the sI(AHP). We have previously shown that
      learning-induced AHP reduction is maintained by persistent protein kinase C (PKC)
      and extracellular regulated kinase (ERK) activation. However, the molecular
      machinery underlying this long-lasting modulation of intrinsic excitability is
      yet to be fully described. Here we examine whether the CaMKII, which is known to
      be crucial in learning, memory and synaptic plasticity processes, is instrumental
      for the maintenance of learning-induced AHP reduction. KN93, that selectively
      blocks CaMKII autophosphorylation at Thr286, reduced the AHP in neurons from
      trained and control rat to the same extent. Consequently, the differences in AHP
      amplitude and neuronal adaptation between neurons from trained rats and controls
      remained. Accordingly, the level of activated CaMKII was similar in pirifrom
      cortex samples taken form trained and control rats. Our data show that although
      CaMKII modulates the amplitude of AHP of pyramidal neurons in the piriform
      cortex, its activation is not required for maintaining learning-induced
      enhancement of neuronal excitability.

PMID- 19172998
TI  - Heterochrony and cross-species intersensory matching by infant vervet monkeys.
AB  - BACKGROUND: Understanding the evolutionary origins of a phenotype requires
      understanding the relationship between ontogenetic and phylogenetic processes.
      Human infants have been shown to undergo a process of perceptual narrowing during
      their first year of life, whereby their intersensory ability to match the faces
      and voices of another species declines as they get older. We investigated the
      evolutionary origins of this behavioral phenotype by examining whether or not
      this developmental process occurs in non-human primates as well.
      METHODOLOGY/PRINCIPAL FINDINGS: We tested the ability of infant vervet monkeys
      (Cercopithecus aethiops), ranging in age from 23 to 65 weeks, to match the faces
      and voices of another non-human primate species (the rhesus monkey, Macaca
      mulatta). Even though the vervets had no prior exposure to rhesus monkey faces
      and vocalizations, our findings show that infant vervets can, in fact, recognize
      the correspondence between rhesus monkey faces and voices (but indicate that they
      do so by looking at the non-matching face for a greater proportion of overall
      looking time), and can do so well beyond the age of perceptual narrowing in human
      infants. Our results further suggest that the pattern of matching by vervet
      monkeys is influenced by the emotional saliency of the Face+Voice combination.
      That is, although they looked at the non-matching screen for Face+Voice
      combinations, they switched to looking at the matching screen when the Voice was
      replaced with a complex tone of equal duration. Furthermore, an analysis of
      pupillary responses revealed that their pupils showed greater dilation when
      looking at the matching natural face/voice combination versus the face/tone
      combination. CONCLUSIONS/SIGNIFICANCE: Because the infant vervets in the current
      study exhibited cross-species intersensory matching far later in development than
      do human infants, our findings suggest either that intersensory perceptual
      narrowing does not occur in Old World monkeys or that it occurs later in
      development. We argue that these findings reflect the faster rate of neural
      development in monkeys relative to humans and the resulting differential
      interaction of this factor with the effects of early experience.

PMID- 19172999
TI  - A role for the juxtamembrane cytoplasm in the molecular dynamics of focal
      adhesions.
AB  - Focal adhesions (FAs) are specialized membrane-associated multi-protein complexes
      that link the cell to the extracellular matrix and play crucial roles in cell
      matrix sensing. Considerable information is available on the complex molecular
      composition of these sites, yet the regulation of FA dynamics is largely unknown.
      Based on a combination of FRAP studies in live cells, with in silico simulations
      and mathematical modeling, we show that the FA plaque proteins paxillin and
      vinculin exist in four dynamic states: an immobile FA-bound fraction, an FA
      associated fraction undergoing exchange, a juxtamembrane fraction experiencing
      attenuated diffusion, and a fast-diffusing cytoplasmic pool. The juxtamembrane
      region surrounding FAs displays a gradient of FA plaque proteins with respect to
      both concentration and dynamics. Based on these findings, we propose a new model
      for the regulation of FA dynamics in which this juxtamembrane domain acts as an
      intermediary layer, enabling an efficient regulation of FA formation and
      reorganization.

PMID- 19173000
TI  - Understanding sensory nerve mechanotransduction through localized elastomeric
      matrix control.
AB  - BACKGROUND: While neural systems are known to respond to chemical and electrical
      stimulation, the effect of mechanics on these highly sensitive cells is still not
      well understood. The ability to examine the effects of mechanics on these cells
      is limited by existing approaches, although their overall response is intimately
      tied to cell-matrix interactions. Here, we offer a novel method, which we used to
      investigate stretch-activated mechanotransduction on nerve terminals of sensory
      neurons through an elastomeric interface. METHODOLOGY/PRINCIPAL FINDINGS: To
      apply mechanical force on neurites, we cultured dorsal root ganglion neurons on
      an elastic substrate, polydimethylsiloxane (PDMS), coated with extracellular
      matrices (ECM). We then implemented a controlled indentation scheme using a glass
      pipette to mechanically stimulate individual neurites that were adjacent to the
      pipette. We used whole-cell patch clamping to record the stretch-activated action
      potentials on the soma of the single neurites to determine the
      mechanotransduction-based response. When we imposed specific mechanical force
      through the ECM, we noted a significant neuronal action potential response.
      Furthermore, because the mechanotransduction cascade is known to be directly
      affected by the cytoskeleton, we investigated the cell structure and its effects.
      When we disrupted microtubules and actin filaments with nocodozale or
      cytochalasin-D, respectively, the mechanically induced action potential was
      abrogated. In contrast, when using blockers of channels such as TRP, ASIC, and
      stretch-activated channels while mechanically stimulating the cells, we observed
      almost no change in action potential signalling when compared with mechanical
      activation of unmodified cells. CONCLUSIONS/SIGNIFICANCE: These results suggest
      that sensory nerve terminals have a specific mechanosensitive response that is
      related to cell architecture.

PMID- 19173001
TI  - Derangement of a factor upstream of RARalpha triggers the repression of a
      pleiotropic epigenetic network.
AB  - BACKGROUND: Chromatin adapts and responds to extrinsic and intrinsic cues. We
      hypothesize that inheritable aberrant chromatin states in cancer and aging are
      caused by genetic/environmental factors. In previous studies we demonstrated that
      either genetic mutations, or loss, of retinoic acid receptor alpha (RARalpha),
      can impair the integration of the retinoic acid (RA) signal at the chromatin of
      RA-responsive genes downstream of RARalpha, and can lead to aberrant repressive
      chromatin states marked by epigenetic modifications. In this study we tested
      whether the mere interference with the availability of RA signal at RARalpha, in
      cells with an otherwise functional RARalpha, can also induce epigenetic
      repression at RA-responsive genes downstream of RARalpha. METHODOLOGY/PRINCIPAL
      FINDINGS: To hamper the availability of RA at RARalpha in untransformed human
      mammary epithelial cells, we targeted the cellular RA-binding protein 2 (CRABP2),
      which transports RA from the cytoplasm onto the nuclear RARs. Stable ectopic
      expression of a CRABP2 mutant unable to enter the nucleus, as well as stable
      knock down of endogenous CRABP2, led to the coordinated transcriptional
      repression of a few RA-responsive genes downstream of RARalpha. The chromatin at
      these genes acquired an exacerbated repressed state, or state "of no return".
      This aberrant state is unresponsive to RA, and therefore differs from the
      physiologically repressed, yet "poised" state, which is responsive to RA.
      Consistent with development of homozygosis for epigenetically repressed loci, a
      significant proportion of cells with a defective CRABP2-mediated RA transport
      developed heritable phenotypes indicative of loss of function.
      CONCLUSION/SIGNIFICANCE: Derangement/lack of a critical factor necessary for
      RARalpha function induces epigenetic repression of a RA-regulated gene network
      downstream of RARalpha, with major pleiotropic biological outcomes.

PMID- 19173002
TI  - Altering mucus rheology to "solidify" human mucus at the nanoscale.
AB  - The ability of mucus to function as a protective barrier at mucosal surfaces
      rests on its viscous and elastic properties, which are not well understood at
      length scales relevant to pathogens and ultrafine environmental particles. Here
      we report that fresh, undiluted human cervicovaginal mucus (CVM) transitions from
      an impermeable elastic barrier to non-adhesive objects sized 1 microm and larger
      to a highly permeable viscoelastic liquid to non-adhesive objects smaller than
      500 nm in diameter. Addition of a nonionic detergent, present in vaginal gels,
      lubricants and condoms, caused CVM to behave as an impermeable elastic barrier to
      200 and 500 nm particles, suggesting that the dissociation of hydrophobically
      bundled mucin fibers created a finer elastic mucin mesh. Surprisingly, the
      macroscopic viscoelasticity, which is critical to proper mucus function, was
      unchanged. These findings provide important insight into the nanoscale structural
      and barrier properties of mucus, and how the penetration of foreign particles
      across mucus might be inhibited.

PMID- 19173003
TI  - Circadian control of dendrite morphology in the visual system of Drosophila
      melanogaster.
AB  - BACKGROUND: In the first optic neuropil (lamina) of the fly's visual system,
      monopolar cells L1 and L2 and glia show circadian rhythms in morphological
      plasticity. They change their size and shape during the day and night. The most
      pronounced changes have been detected in circadian size of the L2 axons. Looking
      for a functional significance of the circadian plasticity observed in axons, we
      examined the morphological plasticity of the L2 dendrites. They extend from axons
      and harbor postsynaptic sites of tetrad synaptic contacts from the photoreceptor
      terminals. METHODOLOGY/PRINCIPAL FINDINGS: The plasticity of L2 dendrites was
      evaluated by measuring an outline of the L2 dendritic trees. These were from
      confocal images of cross sections of L2 cells labeled with GFP. They were in wild
      type and clock mutant flies held under different light conditions and sacrified
      at different time points. We found that the L2 dendrites are longest at the
      beginning of the day in both males and females. This rhythm observed under a
      day/night regime (LD) was maintained in constant darkness (DD) but not in
      continuous light (LL). This rhythm was not present in the arrhythmic per(01)
      mutant in LD or in DD. In the clock photoreceptor cry(b) mutant the rhythm was
      maintained but its pattern was different than that observed in wild-type flies.
      CONCLUSIONS/SIGNIFICANCE: The results obtained showed that the L2 dendrites
      exhibit circadian structural plasticity. Their morphology is controlled by the
      per gene-dependent circadian clock. The L2 dendrites are longest at the beginning
      of the day when the daytime tetrad presynaptic sites are most numerous and L2
      axons are swollen. The presence of the rhythm, but with a different pattern in
      cry(b) mutants in LD and DD indicates a new role of cry in the visual system. The
      new role is in maintaining the circadian pattern of changes of the L2 dendrite
      length and shape.

PMID- 19173004
TI  - Developmental and lactational exposure to dieldrin alters mammary tumorigenesis
      in Her2/neu transgenic mice.
AB  - Breast cancer is the most common cancer in Western women and while its precise
      etiology is unknown, environmental factors are thought to play a role. The
      organochlorine pesticide dieldrin is a persistent environmental toxicant thought
      to increase the risk of breast cancer and reduce survival in the human
      population. The objective of this study was to define the effect of developmental
      exposure to environmentally relevant concentrations of dieldrin, on mammary tumor
      development in the offspring. Sexually mature FVB-MMTV/neu female mice were
      treated with vehicle (corn oil), or dieldrin (0.45, 2.25, and 4.5 microg/g body
      weight) daily by gavage for 5 days prior to mating and then once weekly
      throughout gestation and lactation until weaning. Dieldrin concentrations were
      selected to produce serum levels representative of human background body burdens,
      occupational exposure, and overt toxicity. Treatment had no effect on litter
      size, birth weight or the number of pups surviving to weaning. The highest dose
      of dieldrin significantly increased the total tumor burden and the volume and
      number of tumors found in the thoracic mammary glands. Increased mRNA and protein
      expression of the neurotrophin BDNF and its receptor TrkB was increased in tumors
      from the offspring of dieldrin treated dams. This study indicates that
      developmental exposure to the environmental contaminant dieldrin causes increased
      tumor burden in genetically predisposed mice. Dieldrin exposure also altered the
      expression of BNDF and TrkB, novel modulators of cancer pathogenesis.

PMID- 19173005
TI  - Genetic and molecular analysis of wild-derived arrhythmic mice.
AB  - A new circadian variant was isolated by screening the intercross offspring of
      wild-caught mice (Mus musculus castaneus). This variant was characterized by an
      initial maintenance of damped oscillations and subsequent loss of rhythmicity
      after being transferred from light-dark (LD) cycles to constant darkness (DD). To
      map the genes responsible for the persistence of rhythmicity (circadian ratio)
      and the length of free-running period (tau), quantitative trait locus (QTL)
      analysis was performed using F(2) mice obtained from an F(1) cross between the
      circadian variant and C57BL/6J mice. As a result, a significant QTL with a main
      effect for circadian ratio (Arrhythmicity; Arrh-1) was mapped on Chromosome (Chr)
      8. For tau, four significant QTLs, Short free-running period (Sfp-1) (Chr 1), Sfp
      2 (Chr 6), Sfp-3 (Chr 8), Sfp-4 (Chr 11) were determined. An epistatic
      interaction was detected between Chr 3 (Arrh-2) and Chr 5 (Arrh-3). An in situ
      hybridization study of clock genes and mouse Period1::luciferase (mPer1::luc)
      real-time monitoring analysis in the suprachiasmatic nucleus (SCN) suggested that
      arrhythmicity in this variant might not be attributed to core circadian
      mechanisms in the SCN neurons. Our strategy using wild-derived variant mice may
      provide a novel opportunity to evaluate circadian and its related disorders in
      human that arise from the interaction between multiple variant genes.

PMID- 19173006
TI  - Extraction and characterization of essential discharge patterns from multisite
      recordings of spiking ongoing activity.
AB  - BACKGROUND: Neural activation patterns proceed often by schemes or motifs
      distributed across the involved cortical networks. As neurons are correlated, the
      estimate of all possible dependencies quickly goes out of control. The complex
      nesting of different oscillation frequencies and their high non-stationariety
      further hamper any quantitative evaluation of spiking network activities. The
      problem is exacerbated by the intrinsic variability of neural patterns.
      METHODOLOGY/PRINCIPAL FINDINGS: Our technique introduces two important novelties
      and enables to insulate essential patterns on larger sets of spiking neurons and
      brain activity regimes. First, the sampling procedure over N units is based on a
      fixed spike number k in order to detect N-dimensional arrays (k-sequences), whose
      sum over all dimension is k. Then k-sequences variability is greatly reduced by a
      hierarchical separative clustering, that assigns large amounts of distinct k
      sequences to few classes. Iterative separations are stopped when the dimension of
      each cluster comes to be smaller than a certain threshold. As threshold tuning
      critically impacts on the number of classes extracted, we developed an effective
      cost criterion to select the shortest possible description of our dataset.
      Finally we described three indexes (C,S,R) to evaluate the average pattern
      complexity, the structure of essential classes and their stability in time.
      CONCLUSIONS/SIGNIFICANCE: We validated this algorithm with four kinds of
      surrogated activity, ranging from random to very regular patterned. Then we
      characterized a selection of ongoing activity recordings. By the S index we
      identified unstable, moderatly and strongly stable patterns while by the C and
      the R indices we evidenced their non-random structure. Our algorithm seems able
      to extract interesting and non-trivial spatial dynamics from multisource neuronal
      recordings of ongoing and potentially stimulated activity. Combined with time
      frequency analysis of LFPs could provide a powerful multiscale approach linking
      population oscillations with multisite discharge patterns.

PMID- 19173008
TI  - Number-based visual generalisation in the honeybee.
AB  - Although the numerical abilities of many vertebrate species have been
      investigated in the scientific literature, there are few convincing accounts of
      invertebrate numerical competence. Honeybees, Apis mellifera, by virtue of their
      other impressive cognitive feats, are a prime candidate for investigations of
      this nature. We therefore used the well-established delayed match-to-sample
      paradigm, to test the limits of honeybees' ability to match two visual patterns
      solely on the basis of the shared number of elements in the two patterns. Using a
      y-maze, we found that bees can not only differentiate between patterns containing
      two and three elements, but can also use this prior knowledge to differentiate
      three from four, without any additional training. However, bees trained on the
      two versus three task could not distinguish between higher numbers, such as four
      versus five, four versus six, or five versus six. Control experiments confirmed
      that the bees were not using cues such as the colour of the exact configuration
      of the visual elements, the combined area or edge length of the elements, or
      illusory contours formed by the elements. To our knowledge, this is the first
      report of number-based visual generalisation by an invertebrate.

PMID- 19173009
TI  - Modeling mercury deposition through latent space-time processes.
AB  - This paper provides a space-time process model for total wet mercury deposition.
      Key methodological features introduced include direct modeling of deposition
      rather than of expected deposition, the utilization of precipitation information
      (there is no deposition without precipitation) without having to construct a
      precipitation model, and the handling of point masses at 0 in the distributions
      of both precipitation and deposition. The result is a specification that enables
      spatial interpolation and temporal prediction of deposition as well as
      aggregation in space or time to see patterns and trends in deposition.We use
      weekly deposition monitoring data from the NADP/MDN (National Atmospheric
      Deposition Program/Mercury Deposition Network) for 2003 restricted to the eastern
      U.S. and Canada. Our spatio-temporal hierarchical model allows us to interpolate
      to arbitrary locations and, hence, to an arbitrary grid, enabling weekly
      deposition surfaces (with associated uncertainties) for this region. It also
      allows us to aggregate weekly depositions at coarser, quarterly and annual,
      temporal levels.

PMID- 19173010
TI  - PROFILE-KERNEL LIKELIHOOD INFERENCE WITH DIVERGING NUMBER OF PARAMETERS.
AB  - The generalized varying coefficient partially linear model with growing number of
      predictors arises in many contemporary scientific endeavor. In this paper we set
      foot on both theoretical and practical sides of profile likelihood estimation and
      inference. When the number of parameters grows with sample size, the existence
      and asymptotic normality of the profile likelihood estimator are established
      under some regularity conditions. Profile likelihood ratio inference for the
      growing number of parameters is proposed and Wilk's phenomenon is demonstrated. A
      new algorithm, called the accelerated profile-kernel algorithm, for computing
      profile-kernel estimator is proposed and investigated. Simulation studies show
      that the resulting estimates are as efficient as the fully iterative profile
      kernel estimates. For moderate sample sizes, our proposed procedure saves much
      computational time over the fully iterative profile-kernel one and gives stabler
      estimates. A set of real data is analyzed using our proposed algorithm.

PMID- 19173007
TI  - Rapid changes in transcription profiles of the Plasmodium yoelii yir multigene
      family in clonal populations: lack of epigenetic memory?
AB  - The pir multigene family, found in the genomes of Plasmodium vivax, P. knowlesi
      and the rodent malaria species, encode variant antigens that could be targets of
      the immune response. Individual parasites of the rodent malaria Plasmodium
      yoelii, selected by micromanipulation, transcribe only 1 to 3 different pir (yir)
      suggesting tight transcriptional control at the level of individual cells. Using
      microarray and quantitative RT-PCR, we show that despite this very restricted
      transcription in a single cell, many yir genes are transcribed throughout the
      intra-erythrocytic asexual cycle. The timing and level of transcription differs
      between genes, with some being more highly transcribed in ring and trophozoite
      stages, whereas others are more highly transcribed in schizonts. Infection of
      immunodeficient mice with single infected erythrocytes results in populations of
      parasites each with transcriptional profiles different from that of the parent
      parasite population and from each other. This drift away from the original 'set'
      of transcribed genes does not appear to follow a preset pattern and "epigenetic
      memory" of the yir transcribed in the parent parasite can be rapidly lost. Thus,
      regulation of pir gene transcription may be different from that of the well
      characterised multigene family, var, of Plasmodium falciparum.

PMID- 19173011
TI  - Efficacy of Parent Training for Stepfathers: From Playful Spectator and Polite
      Stranger to Effective Stepfathering.
AB  - OBJECTIVE: The primary goal of this paper was to evaluate independent effects of
      stepfather parenting behaviors within the context of a parent training efficacy
      trial designed for recently married couples with children exhibiting behavior
      problems. A secondary goal was to examine measurement properties of a multiple
      method, multiple-source construct of effective stepfathering including direct
      observation. Stepfather hypotheses were derived from a social interaction
      learning model of child adjustment and specifically evaluated the Oregon model of
      Parent Management Training (PMTO) intervention DESIGN: In a randomized control
      trial, 110 recently married families consisting of an early-elementary-school
      aged focal child, biological mother, and stepfather were assessed over 2 years.
      Assessment included direct observation of stepfather - stepchild interactions.
      Analyses first tested intervention effects on change in stepfathering and second
      tested independent effects of stepfathering on change in children's depression
      and noncompliance at follow-ups. RESULTS: The intervention produced medium effect
      sizes at 6 and 12 months for improved stepfathering with parenting effects
      diminishing at 24 months. Hierarchical regression models showed that intervention
      group improvements in stepfathering predicted greater reductions in children's
      depression and noncompliance at 2 years relative to controls, controlling for
      change in mothering. CONCLUSIONS: These findings underscore the preventive
      utility of the PMTO intervention for stepfathers. Implications for research,
      translation, timing of intervention, and implementation are discussed.

PMID- 19173012
TI  - Intracranial hemorrhage during GliaSite RTS manipulation in an anticoagulated
      patient.
AB  - The GliaSite radiation therapy system (RTS) is an implantable balloon
      brachytherapy applicator used to deliver iodine-125 in the treatment of recurrent
      high-grade gliomas. Patients generally tolerate the procedure well, with only
      rare reports of adverse events such as wound infection, meningitis, and
      symptomatic radiation necrosis. Hemorrhagic complications have not been reported.
      We present a case report describing intracranial hemorrhage during GliaSite
      manipulation in a patient receiving long-term anticoagulation for a previously
      diagnosed pulmonary embolism. The GliaSite RTS and the management of venous
      thromboembolism in patients with brain tumors are reviewed. These events suggest
      that normalizing coagulation status during GliaSite balloon inflation and
      deflation should be considered.

PMID- 19173014
TI  - Reconciling symbolic and dynamic aspects of language: Toward a dynamic
      psycholinguistics.
AB  - The present paper examines natural language as a dynamical system. The oft
      expressed view of language as "a static system of symbols" is here seen as an
      element of a larger system that embraces the mutuality of symbols and dynamics.
      Following along the lines of the theoretical biologist H.H. Pattee, the relation
      between symbolic and dynamic aspects of language is expressed within a more
      general framework that deals with the role of information in biological systems.
      In this framework, symbols are seen as information-bearing entities that emerge
      under pressures of communicative needs and that serve as concrete constraints on
      development and communication. In an attempt to identify relevant dynamic aspects
      of such a system, one has to take into account events that happen on different
      time scales: evolutionary language change (i.e., a diachronic aspect), processes
      of communication (language use) and language acquisition. Acknowledging the role
      of dynamic processes in shaping and sustaining the structures of natural language
      calls for a change in methodology. In particular, a purely synchronic analysis of
      a system of symbols as "meaning-containing entities" is not sufficient to obtain
      answers to certain recurring problems in linguistics and the philosophy of
      language. A more encompassing research framework may be the one designed
      specifically for studying informationally based coupled dynamical systems
      (coordination dynamics) in which processes of self-organization take place over
      different time scales.

PMID- 19173013
TI  - Moving to higher ground: The dynamic field theory and the dynamics of visual
      cognition.
AB  - In the present report, we describe a new dynamic field theory that captures the
      dynamics of visuo-spatial cognition. This theory grew out of the dynamic systems
      approach to motor control and development, and is grounded in neural principles.
      The initial application of dynamic field theory to issues in visuo-spatial
      cognition extended concepts of the motor approach to decision making in a sensori
      motor context, and, more recently, to the dynamics of spatial cognition. Here we
      extend these concepts still further to address topics in visual cognition,
      including visual working memory for non-spatial object properties, the processes
      that underlie change detection, and the 'binding problem' in vision. In each
      case, we demonstrate that the general principles of the dynamic field approach
      can unify findings in the literature and generate novel predictions. We contend
      that the application of these concepts to visual cognition avoids the pitfalls of
      reductionist approaches in cognitive science, and points toward a formal
      integration of brains, bodies, and behavior.

PMID- 19173017
TI  - Balancing the art and science of medical practice.

PMID- 19173016
TI  - Continuous non-invasive arterial pressure technique improves patient monitoring
      during interventional endoscopy.
AB  - INTRODUCTION: Close monitoring of arterial blood pressure (BP) is a central part
      of cardiovascular surveillance of patients at risk for hypotension. Therefore,
      patients undergoing diagnostic and therapeutic procedures with the use of
      sedating agents are monitored by discontinuous non-invasive BP measurement
      (NIBP). Continuous non-invasive BP monitoring based on vascular unloading
      technique (CNAP, CN Systems, Graz) may improve patient safety in those settings.
      We investigated if this new technique improved monitoring of patients undergoing
      interventional endoscopy. METHODS: 40 patients undergoing interventional
      endoscopy between April and December 2007 were prospectively studied with CNAP(R)
      in addition to standard monitoring (NIBP, ECG and oxygen saturation). All
      monitoring values were extracted from the surveillance network at one-second
      intervals, and clinical parameters were documented. The variance of CNAP values
      were calculated for every interval between two NIBP measurements. RESULTS: 2660
      minutes of monitoring were recorded (mean 60.1+/-34.4 min/patient). All patients
      were analgosedated with midazolam and pethidine, and 24/40 had propofol infusion
      (mean 90.9+/-70.3 mg). The mean arterial pressure for CNAP was 102.4+/-21.2 mmHg
      and 106.8+/-24.8 mmHg for NIBP. Based on the first NIBP value in an interval
      between two NIBP measurements, BP values determined by CNAP showed a maximum
      increase of 30.8+/-21.7% and a maximum decrease of 22.4+/-28.3% (mean of all
      intervals). DISCUSSION: Conventional intermittent blood pressure monitoring of
      patients receiving sedating agents failed to detect fast changes in BP. The new
      technique CNAP improved the detection of rapid BP changes, and may contribute to
      a better patient safety for those undergoing interventional procedures.

PMID- 19173018
TI  - Congenital megaureter.

PMID- 19173015
TI  - Aberrant p63 and WT-1 expression in myoepithelial cells of pregnancy-associated
      breast cancer: implications for tumor aggressiveness and invasiveness.
AB  - Our recent studies revealed that focal alterations in breast myoepithelial cell
      layers significantly impact the biological presentation of associated epithelial
      cells. As pregnancy-associated breast cancer (PABC) has a significantly more
      aggressive clinical course and mortality rate than other forms of breast
      malignancies, our current study compared tumor suppressor expression in
      myoepithelial cells of PABC and non-PABC, to determine whether myoepithelial
      cells of PABC may have aberrant expression of tumor suppressors. Tissue sections
      from 20 cases of PABC and 20 cases of stage, grade, and age matched non-PABC were
      subjected to immunohistochemistry, and the expression of tumor suppressor maspin,
      p63, and Wilms' tumor 1 (WT-1) in calponin positive myoepithelial cells were
      statistically compared. The expression profiles of maspin, p63, and WT-1 in
      myoepithelial cells of all ducts encountered were similar between PABC and non
      PABC. PABC, however, displayed several unique alterations in terminal duct and
      lobular units (TDLU), acini, and associated tumor tissues that were not seen in
      those of non-PABC, which included the absence of p63 and WT-1 expression in a
      vast majority of the myoepithelial cells, cytoplasmic localization of p63 in the
      entire epithelial cell population of some lobules, and substantially increasing
      WT-1 expression in vascular structures of the invasive cancer component. All or
      nearly all epithelial cells with aberrant p63 and WT-1 expression lacked the
      expression of estrogen receptor and progesterone receptor, whereas they had a
      substantially higher proliferation index than their counterparts with p63 and WT
      1 expression. Hyperplastic cells with cytoplasmic p63 expression often adjacent
      to, and share a similar immunohistochemical and cytological profile with,
      invasive cancer cells. To our best knowledge, our main finings have not been
      previously reported. Our findings suggest that the functional status of
      myoepithelial cells may be significantly associated with tumor aggressiveness and
      invasiveness.

PMID- 19173020
TI  - Omega-3 Fatty Acid supplementation during pregnancy.
AB  - Omega-3 fatty acids are essential and can only be obtained from the diet. The
      requirements during pregnancy have not been established, but likely exceed that
      of a nonpregnant state. Omega-3 fatty acids are critical for fetal
      neurodevelopment and may be important for the timing of gestation and birth
      weight as well. Most pregnant women likely do not get enough omega-3 fatty acids
      because the major dietary source, seafood, is restricted to 2 servings a week.
      For pregnant women to obtain adequate omega-3 fatty acids, a variety of sources
      should be consumed: vegetable oils, 2 low-mercury fish servings a week, and
      supplements (fish oil or algae-based docosahexaenoic acid).

PMID- 19173019
TI  - Human papillomavirus-related gynecologic neoplasms: screening and prevention.
AB  - The recent recognition of oncogenic human papillomavirus (HPV) as a key component
      of female lower genital tract malignancies has led to significant changes in many
      screening and prevention guidelines for cervical cancer, and, combined with the
      advent of vaccination, will likely have sweeping repercussions on the incidence
      of cervical, vulvar, and vaginal carcinoma. This article focuses on the specific
      principles of cancer screening and prevention with an emphasis on HPV-mediated
      disease.

PMID- 19173021
TI  - The impact of maternal obesity on maternal and fetal health.
AB  - The increasing rate of maternal obesity provides a major challenge to obstetric
      practice. Maternal obesity can result in negative outcomes for both women and
      fetuses. The maternal risks during pregnancy include gestational diabetes and
      preeclampsia. The fetus is at risk for stillbirth and congenital anomalies.
      Obesity in pregnancy can also affect health later in life for both mother and
      child. For women, these risks include heart disease and hypertension. Children
      have a risk of future obesity and heart disease. Women and their offspring are at
      increased risk for diabetes. Obstetrician-gynecologists are well positioned to
      prevent and treat this epidemic.

PMID- 19173022
TI  - Listeriosis in pregnancy: diagnosis, treatment, and prevention.
AB  - Listeriosis is a rare disease that causes mild maternal illness, but can be
      devastating to the fetus. Listeria's rare microbiologic features make it a
      difficult infection to diagnose and treat: it is an intracellular organism that
      hides within host cells. Because of the potentially severe consequences, it is
      important that obstetricians are familiar with the diagnosis, treatment, and
      prevention of listerial infection.

PMID- 19173023
TI  - A Review of the Proceedings from the 2008 NICHD Workshop on Standardized
      Nomenclature for Cardiotocography: Update on Definitions, Interpretative Systems
      With Management Strategies, and Research Priorities in Relation to Intrapartum
      Electronic Fetal Monitoring.
AB  - Despite evidence demonstrating no neonatal benefit, the medicolegal climate in
      the United States requires obstetricians to integrate continuous intrapartum
      surveillance into their care of the pregnant laboring patient. The intent of this
      article is to familiarize the reader with the most recent, standardized,
      quantitative nomenclature recommended to describe intrapartum CTG in order to
      reduce miscommunication among providers caring for the laboring patient,
      propagate consistent, evidence-based responses to CTG patterns, and systematize
      the terminology used by researchers investigating intrapartum CTG.

PMID- 19173024
TI  - Obstetric fistula: living with incontinence and shame.
AB  - Over 2 million women worldwide have an obstetric fistula, with the majority of
      cases occurring in resource-poor countries. Afflicted women tend to be young,
      primiparous, impoverished, and have little or no access to medical care.
      Incontinent of urine and/or stool, these women become ostracized and shunned by
      their community. Most obstetric fistulas are surgically correctible, although
      surgical outcomes have been poorly studied. Programs that improve nutrition,
      delay the age of marriage, improve family planning, and increase access to
      maternal and obstetric care are necessary to prevent obstetric fistula.

PMID- 19173025
TI  - Growing old.

PMID- 19173026
TI  - Hormone replacement therapy and quality of life.

PMID- 19173027
TI  - Magnesium sulphate and cerebral palsy.

PMID- 19173028
TI  - Levator hiatus damage.

PMID- 19173029
TI  - Snippets.

PMID- 19173030
TI  - Management of severe preeclampsia.

PMID- 19173031
TI  - Comment on "why epidurals do not always work".
AB  - The technique review by Arendt and Segal1in the Spring 2008 issue of Reviews in
      Obstetrics & Gynecology gives us broad insight on various causes of epidural
      analgesia failure. We would like to comment on the subject and share our
      experience.

PMID- 19173033
TI  - Differential expression of neurotrophins in postnatal C57BL/6 mice striatum.
AB  - Neurotrophin expression in early stages of development is crucial for brain
      assembly and function. In particular, postnatal expression of neurotrophins has
      not been well documented in the neostriatum and in general neurotrophins or their
      receptor mRNA's are normally reported, but not protein expression. In the present
      study, immunocytochemical expression of BDNF, NT-3 and NT-4/5 was characterized
      in striatal tissue of C57BL/6 mice at postnatal days 10(th )(P10), 21(st) (P21),
      42(nd) (P42) and 80(th) (P80). We found that the expression of BDNF diminished
      along the postnatal time course we evaluated, while staining for NT-4 increased
      up to age P42 and remained constant, thereafter in the cell's soma. In contrast,
      NT-3 was first expressed in the neostriatal bundles and later on, in neostriatal
      cell somas. These results provide information about differences in the spatial
      and temporal expression of each neurotrophin in the neostriatum during the first
      80(th) postnatal days. RT-PCR procedures were also carried out to further
      determine whether protein levels of neurotrophins observed in the neostriatum
      were under control of gene expression. All neurotrophin mRNAs were expressed and
      only mRNA(BDNF) was reduced during the postnatal evaluated days. Differences in
      temporal expression of neurotrophins may be related to the heterochronic
      development of neostriatal cell populations, but also with the specificity of
      each neurotrophin modulating different neuronal targets.

PMID- 19173032
TI  - The fascinating world of RNA interference.
AB  - Micro- and short-interfering RNAs represent small RNA family that are recognized
      as critical regulatory species across the eukaryotes. Recent high-throughput
      sequencing have revealed two more hidden players of the cellular small RNA pool.
      Reported in mammals and Caenorhabditis elegans respectively, these new small RNAs
      are named piwi-interacting RNAs (piRNAs) and 21U-RNAs. Moreover, small RNAs
      including miRNAs have been identified in unicellular alga Chlamydomonas
      reinhardtii, redefining the earlier concept of multi-cellularity restricted
      presence of these molecules. The discovery of these species of small RNAs has
      allowed us to understand better the usage of genome and the number of genes
      present but also have complicated the situation in terms of biochemical
      attributes and functional genesis of these molecules. Nonetheless, these new
      pools of knowledge have opened up avenues for unraveling the finer details of the
      small RNA mediated pathways.

PMID- 19173034
TI  - Assay validation for KIM-1: human urinary renal dysfunction biomarker.
AB  - Urinary kidney injury molecule (KIM-1) is a sensitive quantitative biomarker for
      early detection of kidney tubular injury. The objective of the present work was
      to analytically validate this urinary renal injury biomarker. Duo-set reagents
      from R&D were used to develop the ELISA and validate the assay's linearity, intra
      run precision, inter-run precision, lower limit of quantification, recovery,
      dilutional verification, reference range, stability, and length of run. The
      reference range data suggests that the healthy population falls within the assay
      range (59 - 2146 pg/mL) and upper limit of quantitation for this assay is 17168
      pg/mL for the patient population. This is a robust assay to detect urinary levels
      of KIM-1, which serves as a non-invasive sensitive, reproducible, and potentially
      high-throughput method to detect early kidney injury in drug development studies.

PMID- 19173035
TI  - Antitumor activity of T cells generated from lymph nodes draining the SEA
      expressing murine B16 melanoma and secondarily activated with dendritic cells.
AB  - The successful use of tumor-draining lymph nodes (TDLN) as a source of effector
      cells for cancer immunotherapy depends largely on the immunogenicity of the tumor
      drained by the lymph nodes as well as the methods for secondary in vitro T cell
      activation and expansion. We transferred the bacterial superantigen
      staphylococcal enterotoxin A (SEA) gene into B16 murine melanoma tumor cells, and
      used them to induce TDLN (SEA TDLN) in syngeneic hosts. Wild-type (wt) TDLN
      induced by parental B16 tumor was used as a control. In vitro, SEA TDLN cells
      proliferated more vigorously, produced more IFN gamma and demonstrated higher CTL
      activity than wt TDLN cells when activated with anti-CD3/anti-CD28/IL-2. In vivo,
      SEA TDLN cells mediated tumor eradication more effectively than similarly
      activated wt TDLN cells (p<0.01). Furthermore, use of dendritic cells (DC) plus
      tumor antigen in vitro in addition to anti-CD3/anti-CD28/IL-2 stimulation further
      amplified the immune function and therapeutic efficacy of SEA TDLN cells. DC
      stimulated SEA TDLN cells eliminated nearly 90% of the pulmonary metastasis in
      mice bearing established B16 melanoma micrometastases. These results indicate
      that enforced expression of superantigen SEA in poorly immunogenic tumor cells
      can enhance their immunogenicity as a vaccine in vivo. The combined use of
      genetically modified tumor cells as vaccine to induce TDLN followed by secondary
      stimulation using antigen-presenting cells and tumor antigen in a sequential
      immunization/activation procedure may represent a unique method to generate more
      potent effector T cells for adoptive immunotherapy of cancer.

PMID- 19173036
TI  - SIRT1, is it a tumor promoter or tumor suppressor?
AB  - SIRT1 has been considered as a tumor promoter because of its increased expression
      in some types of cancers and its role in inactivating proteins that are involved
      in tumor suppression and DNA damage repair. However, recent studies demonstrated
      that SIRT1 levels are reduced in some other types of cancers, and that SIRT1
      deficiency results in genetic instability and tumorigenesis, while overexpression
      of SIRT1 attenuates cancer formation in mice heterozygous for tumor suppressor
      p53 or APC. Here, I review these recent findings and discuss the possibility that
      activation of SIRT1 both extends lifespan and inhibits cancer formation.

PMID- 19173037
TI  - Activity of Chitosans in combination with antibiotics in Pseudomonas aeruginosa.
AB  - Chitosan and its derivative water soluble Chitosan oligosaccharide are used in a
      variety of applications in pharmaceutical preparations. In this study, 2 wild
      (ATCC 15729 and PAO1) and 2 mutant strains (PT121 and PT149) of P. aeruginosa are
      investigated for drug-drug interactions in vitro. 10 antimicrobial agents
      (antibiotics) are combined with different degree of deacetylated Chitosans and
      Chitosan oligosaccharide. All the chitosans show synergistic activity with
      sulfamethoxazole, a sulfonamide antimicrobial agent. It is interesting to observe
      that the MIC value for the MexEF-OprN overexpressing mutant strain of P.
      aeruginosa is 5 fold higher than the other strains under investigation suggesting
      a possible role of this efflux pump in Sulfamethoxazole efflux. The findings
      suggest on the use of chitosans as enhancing agent in combination with
      antibiotics in pharmaceutical preparations.

PMID- 19173039
TI  - Isotope Ratio Mass Spectrometry.
AB  - Isotope Ratio Mass Spectrometry (IRMS) is a specialized technique used to provide
      information about the geographic, chemical, and biological origins of substances.
      The ability to determine the source of an organic substance stems from the
      relative isotopic abundances of the elements which comprise the material. Because
      the isotope ratios of elements such as carbon, hydrogen, oxygen, sulfur, and
      nitrogen can become locally enriched or depleted through a variety of kinetic and
      thermodynamic factors, measurement of the isotope ratios can be used to
      differentiate between samples which otherwise share identical chemical
      compositions. Several sample introduction methods are now available for
      commercial isotope ratio mass spectrometers. Combustion is most commonly used for
      bulk isotopic analysis, whereas gas and liquid chromatography are predominately
      used for the real-time isotopic analysis of specific compounds within a mixture.
      Here, highlights of advances in instrumentation and applications within the last
      three years are provided to illustrate the impact of this rapidly growing area of
      research. Some prominent new applications include authenticating organic food
      produce, ascertaining whether or not African elephants are guilty of night-time
      raids on farmers' crops, and linking forensic drug and soil samples from a crime
      scene to a suspected point of origin. For the sake of brevity, we focus this
      Minireview on the isotope ratio measurements of lighter-elements common to
      organic sources; we do not cover the equally important field of inorganic isotope
      ratio mass spectrometry.

PMID- 19173038
TI  - Understanding quantitative genetics in the systems biology era.
AB  - Biology is now entering the new era of systems biology and exerting a growing
      influence on the future development of various disciplines within life sciences.
      In early classical and molecular periods of Biology, the theoretical frames of
      classical and molecular quantitative genetics have been systematically
      established, respectively. With the new advent of systems biology, there is
      occurring a paradigm shift in the field of quantitative genetics. Where and how
      the quantitative genetics would develop after having undergone its classical and
      molecular periods? This is a difficult question to answer exactly. In this
      perspective article, the major effort was made to discuss the possible
      development of quantitative genetics in the systems biology era, and for which
      there is a high potentiality to develop towards "systems quantitative genetics".
      In our opinion, the systems quantitative genetics can be defined as a new
      discipline to address the generalized genetic laws of bioalleles controlling the
      heritable phenotypes of complex traits following a new dynamic network model.
      Other issues from quantitative genetic perspective relating to the genetical
      genomics, the updates of network model, and the future research prospects were
      also discussed.

PMID- 19173040
TI  - Algal biosensor array on a single electrode.
AB  - An algal array was prepared on a single transparent electrode, and photosynthetic
      activity of each algal channel and its inhibition by a toxin were monitored with
      a single-channel potentiostat by successive light irradiation with a LED array.

PMID- 19173041
TI  - Electrophoretic field gradient focusing with on-column detection by fluorescence
      quenching.
AB  - Native, uncoloured, proteins can be focused in a column containing a fluorescent
      packing material, using hydrodynamic flow and a counteracting non-linear electric
      field, and imaged along the length of the channel by fluorescence quenching.

PMID- 19173042
TI  - Immunosensing system for alpha-fetoprotein through boronate immunoaffinity column
      in combination with flow injection chemiluminescence.
AB  - A novel immunosensing system for determination of human alpha-fetoprotein (AFP)
      was proposed by using a boronate immunoaffinity column as the glycated antigen
      collector in combination with flow injection chemiluminescence. The column was
      fabricated by filling boronic acid-modified sepharose gel into a glass tube. With
      a sugar-boronic acid interaction, the AFP antigen could be effectively
      immobilized on the sepharose gel matrix. After an off-line incubation, the
      mixture of the analyte AFP and horseradish peroxidase-labeled AFP antibody (HRP
      anti-AFP) was injected into the column. The free HRP-anti-AFP was trapped by the
      immobilized antigen in the column and detected via chemiluminescence due to its
      sensitive effect on the reaction of luminol and hydrogen peroxide. A calibration
      curve with two linear ranges of 5-120 and 300-1000 ng mL(-1) was obtained under
      the optimized conditions. The whole assay process including regeneration of the
      reactor can be completed in 36 min. The presented immunoassay exhibited a high
      sensitivity, a wide linear range, a low interference with other antigens and a
      good reproducibility. It is potentially used to detect the serum AFP level in
      clinical diagnosis.

PMID- 19173043
TI  - A micro-thermoelectric gas sensor for detection of hydrogen and atomic oxygen.
AB  - This paper demonstrates the fabrication and performance of a micro-thermoelectric
      gas sensor for an effective and inexpensive gas analysis system. The proposed
      micro-thermoelectric gas sensor was fabricated by using a surface micromachining
      technique. The sensing mechanism, consisting of thermoelectric material and a
      novel metal catalyst, was fabricated on the highly thermally resistive layer for
      reduced heat transfer to the substrate allowing for a simple fabrication process.
      The micro-thermoelectric gas sensor detects target gas species by measuring the
      reaction heat of the catalytic reaction between the target gas and a novel metal
      catalyst using Cu-Bi thermopiles. The catalytic reaction occurs only on the hot
      junction of the sensing thermopile where the metal catalyst is deposited. In
      order to reduce the external thermal noise, a difference between the output
      voltage of the sensing and the reference thermopiles was measured by using a
      differential amplifier. The response of the fabricated sensor was linear to
      temperature difference. The fabricated sensor can be used to detect various
      concentrations of hydrogen and atomic oxygen, where the output voltage linearly
      increased with the gas concentration.

PMID- 19173044
TI  - Optical feedback cavity enhanced absorption spectroscopy with diode lasers.
AB  - An optical feedback cavity enhanced absorption spectroscopy (OF-CEAS) apparatus
      has been developed, using a distributed feedback diode laser centred close to a
      wavelength of 1596 nm. Light from a V-shaped optical cavity is allowed to feed
      back to the laser diode, injection seeding the laser at the cavity mode
      frequencies, and bringing about linewidth narrowing and frequency locking to the
      cavity resonance. The OF-CEAS technique's expediency and sensitivity have been
      demonstrated, first on measurements of aerial water absorptions close to 6260.8
      cm(-)(1), and then on two carbon dioxide absorptions close to 6261.7 cm(-)(1)
      which may be used to measure the concentrations of (13)CO(2) and (12)CO(2)
      isotopologues in a CO(2) sample. Employing a cavity of moderate finesse (F
      approximately 3500), an acquisition time-reduced minimum detectable absorption
      coefficient of 5.8 x 10(-)(9) cm(-)(1) s(1/2) has been determined.

PMID- 19173045
TI  - Determination of hydroxyl rate constants by a high-throughput fluorimetric assay:
      towards a unified reactivity scale for antioxidants.
AB  - We describe in this article the development of a new method for the determination
      of rate constants of reaction of the hydroxyl radical, generated by radiolysis of
      water, with almost any possible molecule. It has been designed to provide a fast
      and reliable screening of antioxidant banks using microplates. Our particular
      approach is based on the use of the coumarin molecule as a competitor against the
      tested molecules: after a fast pulse of low dose irradiation, the fluorescence of
      7-hydroxycoumarin produced by the oxidation of coumarin is measured and is
      inversely proportional to the scavenging ability of the tested antioxidant. We
      have validated our protocol using 32 molecules whose rate constants with HO had
      already been evaluated and found a good agreement between our rate constants and
      the latter ones. The scopes and limitations of our method, as well as those of
      other rate constant determination methods, are discussed.

PMID- 19173046
TI  - Design and characterization of immunogens for raising antibodies directed towards
      chelated alkali metals.
AB  - The properties of immunogens synthesized from a calix[4]crown-6 were investigated
      with the aim of generating specific antibodies towards caesium chelates. Affinity
      capillary electrophoresis was successfully used to determine the stability
      parameters with caesium of both the hapten and the corresponding immunogens after
      coupling to bovine serum albumin (BSA). Unfortunately, the stability of the
      caesium chelate was shown to decrease drastically as the polarity of the medium
      increased. Nevertheless, the selectivity was proved to be rather stable, with a
      clear preference of caesium over potassium. The binding mechanism for the protein
      conjugates proved to be complex, as revealed by isotherms, whatever the number of
      calixarene groups coupled to BSA. Immunization of mice with caesium loaded
      immunogen resulted in the production of polyclonal antibodies able to distinguish
      between free calixarene and its complexes with either potassium or caesium.

PMID- 19173047
TI  - A weighted multiscale regression for multivariate calibration of near infrared
      spectra.
AB  - A weighted multiscale regression for building a combined model in multivariate
      calibration of near infrared spectra is proposed. In the approach, the spectra
      are decomposed into different scale blocks (or frequency components) by wavelet
      transform (WT) at first, then partial least squares (PLS) models are built with
      the decomposed components, and at last a combined model is built by a weighted
      averaging. The weight of each model is determined by the prediction residual
      error sum of squares (PRESS) value obtained with Monte Carlo cross validation
      (MCCV). The underlying philosophy of the strategy is that useful information may
      be embedded in all the components obtained by WT, although the higher and lower
      frequency components mainly represent noise and background, respectively. To
      validate the effectiveness and universality of the proposed method, it was
      applied to two different sets of near-infrared (NIR) spectra of tobacco lamina.
      Compared with the results obtained with commonly used PLS methods, the proposed
      method is proved to be a high-performance tool for multivariate calibration of
      complex NIR spectra.

PMID- 19173048
TI  - Predicting skin permeability using liposome electrokinetic chromatography.
AB  - The potential of liposome electrokinetic chromatography (LEKC), which is applied
      to estimate compound penetration through the skin, was evaluated in this report.
      Quantitative retention-activity relationships (QRARs) were successfully
      constructed between the compound skin permeability coefficient (log K(p)) and the
      retention values (log k), as well as some calculated molecular descriptors by the
      stepwise regression method (R(2) = 0.902). Furthermore, the developed vector
      method was applied to compare the similarity between the reported lipophilicity
      measuring scales and compounds through the skin. Both results indicated that the
      transport of a compound into the liposomal membrane was more similar to its
      penetration through the skin than that into other systems including the octanol
      water system. In a word, LEKC is a promising simple method to predict drug
      penetration through the skin.

PMID- 19173049
TI  - Combining chemical reduction with an electrochemical technique for the
      simultaneous detection of Cr(vi), Pb(ii) and Cd(ii).
AB  - This work herein reports the approach for the simultaneous determination of heavy
      metal ions including cadmium (Cd(ii)), lead (Pb(ii)), and chromium (Cr(vi)) using
      a bismuth film electrode (BFE) by anodic stripping voltammertry (ASV). The BFE
      used was plated in situ. Due to the reduction of Cr(vi) with H(2)O(2) in the acid
      medium, on one hand, the Cr(iii) was produced and Cr(vi) was indirectly detected
      by monitoring the content of Cr(iii) using square-wave ASV. On the other hand,
      Pb(ii) was also released from the complex between Pb(ii) and Cr(vi). Furthermore,
      the coexistence of the Cd(ii) was also simultaneously detected with Pb(ii) and
      Cr(vi) in this system as a result of the formation of an alloy with Bi. The
      detection limits of this method were 1.39 ppb for Cd(ii), 2.47 ppb for Pb(ii) and
      5.27 ppb for Cr(vi) with a preconcentration time of 120 s under optimal
      conditions (S/N = 3), respectively. Furthermore, the sensitivity of this method
      can be improved by controlling the deposition time or by using a cation-exchange
      polymer (such as Nafion) modified electrode.

PMID- 19173050
TI  - Magnetic susceptibility measurement of a microdroplet interface using a magnetic
      circuit.
AB  - A conventional method to measure the magnetic susceptibility of a microdroplet in
      a glass capillary has been constructed by using a magnetic circuit (2.82 T) with
      a high magnetic field gradient (B(dB/dz) = 3900 T(2)/m). The magnetophoretic
      velocity of a toluene droplet with ferrocene dispersed in 1 M HCl aqueous
      solution including K(3)[Fe((III))(CN)(6)], Fe((III))Cl(3) and
      cetyltrimethylammonium bromide (CTAB) was measured and the volume magnetic
      susceptibility of droplets was determined. From the dependence of the magnetic
      susceptibility on the radius of the droplets, the interfacial magnetic
      susceptibility of the droplets adsorbed by Prussian blue aggregates was
      determined. The interfacial concentration of Prussian blue of individual droplet
      calculated from the observed magnetic susceptibility indicated that the
      interfacial concentration of Prussian blue are different even in similar sized
      droplets, suggesting inhomogeneous formation of interfacial aggregates.

PMID- 19173051
TI  - Characterization of a high-performance portable GC with a chemiresistor array
      detector.
AB  - The laboratory characterization of a novel, second-generation portable gas
      chromatograph (GC) prototype designed for trace-level determinations of complex
      mixtures of volatile organic compounds (VOC) is described. The instrument
      incorporates a small, multi-stage adsorbent preconcentrator/injector (PCI), two
      series-coupled separation columns with fast, independent temperature-programming
      capabilities and junction-point pressure/flow control, and a detector consisting
      of an array of microfabricated chemiresistor (CR) sensors coated with thiolate
      monolayer-protected gold nanoparticle films. Response patterns from the CR array
      are used in conjunction with chromatographic retention times to identify eluting
      mixture components. Scrubbed ambient air is used as the carrier gas. Enhancements
      in design relative to a previously reported first-generation prototype instrument
      have led to significant reductions in limits of detection as well as improvements
      in resolution, reliability, flexibility, and convenience. Key features of the
      instrument are characterized, with an emphasis on the tradeoffs in sensor array
      performance associated with operation at different temperatures and flow rates.
      The separation of a preconcentrated mixture of 31 VOCs in < 7 minutes is
      demonstrated. Projected detection limits are in the ppt range for most compounds,
      assuming a 1 L sample volume.

PMID- 19173052
TI  - Discrimination between drug-resistant and non-resistant human melanoma cell lines
      by FTIR spectroscopy.
AB  - We investigated the ability of FTIR-microscopy to define spectral changes between
      drug-sensitive and drug-resistant human melanoma cells. As a model system, a
      resistant melanoma cell line (GAC) was selected with cisplatin from parental (GA)
      cells. Using Fourier transform infrared spectroscopy (FTIR) we investigated the
      ability to differentiate between the resistant variant derived from the sensitive
      parental cell line, in the absence of cisplatin. We determined and validated
      spectral parameters (biomarkers) that differentiated between the two cell lines.
      By applying the principal component analysis (PCA) model, we reduced the original
      data size to six principal components. We detected a significant and consistent
      increase in the cell's DNA/RNA ratio as well as an increase in the lipid/protein
      ratio in the resistant cells. These results strongly support the potential of
      developing FTIR microspectroscopy as a simple, reagent-free method for the
      identification of drug-resistant cells. Rapid detection of tumors resistant to a
      particular drug, should contribute to the ability of the physician to choose an
      effective treatment protocol.

PMID- 19173053
TI  - Imaging mass spectrometry using chemical inkjet printing reveals differential
      protein expression in human oral squamous cell carcinoma.
AB  - Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry
      (IMS) is a recently developed technique that generates molecular profiles usually
      of peptide and protein signals directly from the surface of thin tissue sections
      and can be coupled with automation to generate two-dimensional ion density maps.
      This allows specific information to be obtained on the relative abundance and
      spatial distribution of the analytes of interest. The technique has potential for
      application in many diseases including cancer with respect to elucidating the
      molecular pathology and identifying potential biomarkers. In this proof-of
      principle study we have evaluated inkjet printing of the sinapinic acid matrix
      used for MALDI-IMS directly onto the surface of human oral squamous cell
      carcinoma biopsy specimens. This MS profiling technique produced reproducible
      informative chemical images for clinical pathology. Analysis of the resulting
      protein profiles of highly expressed protein in squamous cell carcinoma of the
      tongue reveals spectral features at approximately 4500 and approximately 8360 Da.

PMID- 19173054
TI  - Ag nanostructures assembled on magnetic particles for ready SERS-based detection
      of dissolved chemical species.
AB  - In this investigation, a novel one-step fabrication of Ag-deposited Fe(2)O(3)
      particles and their application as surface-enhanced Raman scattering (SERS)
      substrates in chemical analyses are demonstrated. To deposit Ag onto them,
      Fe(2)O(3) particles were dispersed in a reaction mixture consisting of ethanolic
      AgNO(3) and butylamine, and then the reaction mixture was incubated and shaken
      for 40 min at 50 degrees C. The Ag-deposited Fe(2)O(3) particles are found to be
      efficient SERS substrates for the vibrational spectroscopic characterization of
      molecular adsorbates prepared in a similar way on silver surfaces; the
      enhancement factor of benzenethiol adsorbed on Ag-deposited Fe(2)O(3) was
      estimated to be about 3 x 10(6). Since the magnetic particles are readily
      recovered from the solution phase without centrifugation and/or filtering, the
      SERS-active magnetic particles are useful especially in the Raman spectroscopic
      analysis of dissolved organic species. We evaluate their performance as SERS
      substrates using benzenethiol, adenine, riboflavin, and naphthalene as model
      compounds; thereby, for instance, adenine could be detected down to 10 nM
      concentrations, and naphthalene was also able to be detected down to 200 nM by
      using pentachlorobenzenethiol-adsorbed Ag-deposited Fe(2)O(3) particles as the
      adsorbent.

PMID- 19173055
TI  - Sequence-specific electrochemical detection of Alicyclobacillus acidoterrestris
      DNA using electroconductive polymer-modified fluorine tin oxide electrodes.
AB  - This study outlines the quantification of low levels of Alicyclobacillus
      acidoterrestris in pure cultures, since this bacterium is not inactivated by
      pasteurization and may remain in industrialized foods and beverages.
      Electroconductive polymer-modified fluorine tin oxide (FTO) electrodes and
      multiple nanoparticle labels were used for biosensing. The detection of A.
      acidoterrestris in pure cultures was performed by reverse transcription
      polymerase chain reaction (RT-PCR) and the sensitivity was further increased by
      asymmetric nested RT-PCR using electrochemical detection for quantification of
      the amplicon. The quantification of nested RT-PCR products by Ag/Au-based
      electrochemical detection was able to detect 2 colony forming units per mL (CFU
      mL(-1)) of spores in pure culture and low detection and quantification limits
      (7.07 and 23.6 nM, respectively) were obtained for the target A. acidoterrestris
      on the electrochemical detection bioassay.

PMID- 19173056
TI  - Use of the thyrocyte sodium iodide symporter as the basis for a perchlorate cell
      based assay.
AB  - Perchlorates are strong oxidants widely employed in military and civilian
      energetic materials and recently have been scrutinized as persistent
      environmental pollutants. The perchlorate anion, ClO(4)(-), is a well-known and
      potent competitive inhibitor of iodide transport by the sodium iodide symporter
      (NIS) expressed in the basolateral membranes of thyroid follicular cells
      (thyrocytes). Iodide uptake by thyroid follicular cells is rapid and
      reproducible. The competitive radiotransporter assay in this study shows promise
      as a rapid and convenient method to assay for ClO(4)(-) in water samples at the
      nM level. This work describes the initial efforts to define the assay conditions
      that enhance NIS selectivity for ClO(4)(-). Experiments of 10 min co-incubation
      of ClO(4)(-) and (125)I(-) demonstrate a more significant effect on (125)I(-)
      transport, with a quantifiable ClO(4)(-) concentration range of 50 nM (5 ppb) to
      2 microM (200 ppb), and IC(50) of 180 nM (18 ppb), nearly three-fold lower than
      previous reports. Since the IC(50) in our assay for other known competitor anions
      (SCN(-), ClO(3)(-), NO(3)(-)) remains unchanged from previous research, the
      increased sensitivity for ClO(4)(-) also produces a three-fold enhancement in
      selectivity. In addition to the possible applicability of the thyrocyte to the
      development of a cellular perchlorate biosensor, we propose that the high
      affinity of the NIS for ClO(4)(-) also creates the potential for exploiting this
      membrane protein as a selective, sensitive, and broadly applicable biomechanical
      mechanism for controlled movement and concentration of perchlorate.

PMID- 19173057
TI  - Optimization and evaluation of networked single-wall carbon nanotubes as a NO(2)
      gas sensing material.
AB  - We have prepared conductometric NO(2) gas sensors based on single-wall carbon
      nanotube (SWNT) networks. The SWNT properties are modified systematically by
      varying the annealing temperature between 350 to 550 degrees C under vacuum.
      Thermal annealing is not only necessary to remove dispersant used for nanotube
      dispersion but also plays an important role in optimizing the gas sensing
      abilities. In this paper, the sensing performance is evaluated through three
      crucial sensing characteristics: sensitivity to NO(2), humidity interfering
      effect, and sensor stability over repeated use, all examined at room temperature.
      The sensor annealed at 400 degrees C shows the highest NO(2) sensitivity because
      of the structural properties, i.e., high specific surface area and the molecular
      geometry of having all carbon atoms at the tube-surface. The sensor also shows
      negligible humidity interfering effect and high sensor stability, originating
      from the hydrophobicity and chemical stability of the material, respectively. In
      contrast, annealing temperatures higher than 400 degrees C lead to structural
      defects in SWNTs and thus lower the sensing performance. We experimentally
      confirm that these SWNT characteristics make SWNTs a suitable gas sensing
      material from a practical perspective.

PMID- 19173058
TI  - Dihexadecyldimethylammonium hydroxide admicelles on silica for the
      preconcentration of selected phenols.
AB  - Admicelle based extractions, where sorbents used are prepared by immobilizing
      charged surfactants in a bilayer arrangement onto a silica or aluminum oxide
      surface, have been used for preconcentrating a wide variety of analytes. These
      analytes have a certain degree of hydrophobicity interacting with the alkyl
      chains of the surfactant or they are counter-charged interacting
      electrostatically with the charged polar group of the surfactant. Weakly
      hydrophobic molecules are more challenging to efficiently extract onto this type
      of medium. Presented is an admicelle extraction procedure for extracting weak
      acid phenols. An acid-base reaction takes place between modified surfactants
      containing hydroxide counter ions and weak acid phenols. The result of this
      reaction is the production of phenolate ions that remain counter to the cationic
      surfactant. The acid-base reaction together with the fluid nature of the
      surfactant phase protects the phenolate ions from being removed by counter ions
      in natural solutions. High extraction efficiencies result.

PMID- 19173060
TI  - Investigating the concept of diffusional independence. Potential step transients
      at nano- and micro-electrode arrays: theory and experiment.
AB  - Microelectrode arrays find broad application in electroanalysis offering the
      enhanced sensitivity associated with microelectrodes, but with a high total
      current output. Such arrays are often constructed to make the electrodes
      'diffusionally independent'. To emphasize that this is a time dependent property,
      a two-dimensional simulation, in conjunction with the diffusional domain
      approach, is used to model potential step transient currents at microelectrode
      arrays. Two types of array, hexagonal and cubic, are considered. In both cases
      the absolute (not relative) microelectrode separation distance has a significant
      effect on transient current. Three different regimes of transient current versus
      time can be observed at microelectrode arrays. At short times the transient
      response of isolated microelectrodes is seen, then at intermediate times the
      steady-state response of independent electrodes can be observed. At longer times
      planar diffusion to the entire array takes over. It follows that only at
      timescales corresponding to the first two regimes can the electrodes be
      considered as diffusionally independent. To verify the theory the potential step
      experiment is performed at a regularly spaced hexagonal iridium microdisk array.
      Theory is found to be in a good agreement with the experimental results.

PMID- 19173059
TI  - Artificial-enzyme gel membrane-based biosurveillance sensor with high
      reproducibility and long-term storage stability.
AB  - We propose that the most sophisticated strategy for primary biosurveillance is to
      exploit structural commonality through the detection of biologically relevant
      phosphoric substances. A novel assay, an artificial-enzyme membrane was designed
      and synthesized for sensor fabrication. This artificial-enzyme catalyzes the
      hydrolysis of the diphosphoric acid anhydride structure. This structure
      selective, albeit not molecule-selective, catalytic hydrolysis was successfully
      coupled with amperometric detection. Since the catalytic reaction produces a
      dephosphorylation product (PO(4)(3-)), it can be reduced by an electrode
      potential of -250 mV vs. Ag/AgCl. Owing to the structural selectivity of the
      artificial-enzyme membrane, the sensor can detect biological phosphoric
      substances comprehensively that have the diphosphoric acid anhydride structure.
      The sensor successfully determined various biological phosphoric substances at
      concentrations in the micromolar (microM) to millimolar (mM) range, and it showed
      good functional stability and reproducibility in terms of sensor responses. This
      sensor was used to detect Escherichia coli lysed by heat treatment, and the
      response increased with increasing bacterial numbers. This unique technique for
      analyzing molecular commonality can be applied to the surveillance of
      biocontaminants, e.g. microorganisms, spores and viruses. Artificial-enzyme-based
      detection is a novel strategy for practical biosurveillance in the front line.

PMID- 19173061
TI  - Bienzymatic-based electrochemical DNA biosensors: a way to lower the detection
      limit of hybridization assays.
AB  - The use of the alkaline phosphatase (AP) as an enzyme label and the amplification
      of its analytical response with a diaphorase (DI) secondary enzyme were
      investigated in an electrochemical hybridization assay involving arrays of carbon
      screen-printed DNA biosensors for the sensitive quantification of an amplified
      406-base pair human cytomegalovirus DNA sequence (HCMV DNA). For this purpose,
      PCR-amplified biotinylated HCMV DNA targets were simultaneously bound to a
      monolayer of neutravidin irreversibly adsorbed on the surface of the electrodes
      and hybridized to complementary digoxigenin-labeled detection probes. The amount
      of hybrids immobilized on the electrode surface was labeled with an anti
      digoxigenin AP conjugate and quantified electrochemically by measuring the
      activity of the AP label through the hydrolysis of the electroinactive p
      aminophenylphosphate (PAPP) substrate into the p-aminophenol (PAP) product. The
      intensity of the cyclic voltammetric anodic peak current resulting from the
      oxidation of PAP into p-quinoneimine (PQI) was related to the number of viral
      amplified DNA targets present in the sample, and a detection limit of 10 pM was
      thus achieved. The electrochemical response of the AP label product was further
      enhanced by adding the diaphorase enzymatic amplifier in the solution. In the
      presence of the auxiliary enzyme DI, the PQI was reduced back to PAP and the
      resulting oxidized form of DI was finally regenerated in its reduced native state
      by its natural substrate, NADH. Such a bienzymatic amplification scheme enabled a
      100-fold lowering of the HCMV DNA detection limit obtained with the monoenzymatic
      system.

PMID- 19173062
TI  - Droplet detector for the continuous flow luminol-hydrogen peroxide
      chemiluminescence system.
AB  - A droplet detector with high sensitivity and low consumption of reagents and
      sample for continuous flow chemiluminescence (CL) detection has been developed.
      The proposed system directly mixes sample with luminescence reagents to form a
      small droplet, thanks to the gravity force and surface tension of water, in front
      of a photomultiplier tube (PMT) where the CL reaction takes place. The PMT can
      then instantaneously record the maximum CL light signal emitted from the whole
      reaction process. This small droplet can replace the conventional spiral-shaped
      flow cell for flow injection CL analysis and the droplet detector can reduce
      interference from the reaction products and residual reagents. To evaluate the
      potential application of the proposed detector, the CL detection of Fe(ii) was
      assessed under the alkaline luminol-hydrogen peroxide conditions. The CL
      intensity increased linearly with the concentration of Fe(ii) ranging from 10.0
      to 1000 nmol dm(-3) with a detection limit of 7.16 nmol dm(-3) (S/N = 3). The
      droplet detector allows highly sensitive, stable and fast CL detection of
      analytes, and thus is promising for application to other analytes having fast CL
      reaction rates.

PMID- 19173063
TI  - Application of yeast imprinting in biotechnology and process control.
AB  - Rapid advancements in biotechnology depend on the development of reliable sensing
      sytems adaptable to a variety of analytes. Molecularly imprinted polymers
      combined with mass-sensitive devices (10 MHz QCMs) provide a reliable and robust
      method to observe cell growth and allow cell specifications in real-time. Such
      biosensors selectively detect fermenting yeast in a complex matrix and 10(4)
      cells/microl in solution correspond to an adhesion of approximately 3 x 10(3)
      cells on the sensor coating. Over a period of up to 40 hours, the growth of the
      microorganism at 30 degrees C was observed in various nutrient solutions of
      glucose, peptone and ammonium sulfate, thereby rendering the determination of
      optimum growth conditions possible. While almost no change, i.e. no cell
      propagation, occurred in the absence of glucose, the frequency decreases to more
      than 700 Hz under rich conditions. Increasing the depth of the imprints to more
      than 1.5 microm the yeast cells are so strongly bound that they are fixed in the
      material. With such gravimetric sensors, for instance osmotic effects of cells
      can be followed by a frequency change of 3 kHz by altering the ion strength by
      0.1 M.

PMID- 19173064
TI  - A highly sensitive acidic pH fluorescent probe and its application to HepG2
      cells.
AB  - A novel acidic fluorescent probe 1 has been designed, synthesized, characterized
      and evaluated in vivo as optical imaging of intracellular H(+). The design
      strategy for the probe is based on the change in structure between spirocyclic
      (non-fluorescent) and ring-open (fluorescent) forms of rhodamine dyes. The probe
      exhibits high sensitivity, good photostability, excellent cell membrane
      permeability and strong pH dependence. The pH titration indicates that the
      fluorescence intensity increases more than 100-fold within the pH range of 4.2
      6.0 with the pK(a) value of 4.85, which is valuable for studying acidic
      organelles in living cells. The fluorescent imaging of HepG2 cells also
      demonstrates that the designed probe has great value in monitoring intracellular
      H(+) within living cells.

PMID- 19173065
TI  - Selective detection of endogenous thiols using microchip-based flow analysis and
      mercury/gold amalgam microelectrodes.
AB  - This paper describes the fabrication and characterization of thin-layer
      mercury/gold amalgam microelectrodes and their integration with microchip-based
      flow injection analysis. This microchip platform allows on-chip injection and
      lysis of erythrocytes followed by selective detection of intracellular
      glutathione (GSH) at low potentials. The thin-layer gold microelectrodes were
      amalgamated by electrodeposition of mercury. The electrodes produced a linear
      response for both GSH and cysteine in flow injection analysis studies utilizing
      both off-chip and on-chip injection. Comparative experiments using diamide and on
      chip injection were performed to demonstrate the ability of the microchip device
      to detect changes in GSH concentration. Finally, rabbit erythrocyte samples (2%
      hematocrit) were injected and lysed on-chip and the amount of GSH detected
      corresponded to 312 amol/cell, which is in agreement with previously reported
      values. The selectivity, short time between injection and detection
      (approximately 5 s), and the continuous introduction of sample to the on-chip
      injector should enable the study of dynamically changing systems such as the
      glutathione redox system found in erythrocytes.

PMID- 19173066
TI  - Rapid ultrasensitive measurement of salivary cortisol using nano-linker chemistry
      coupled with surface plasmon resonance detection.
AB  - Cortisol detection in saliva is of great interest for the diagnosis of various
      disease states and the monitoring of stress in humans. Currently, measurements
      are performed predominantly by radioimmunoassay (RIA) which is expensive, labour
      intensive, uses hazardous radioisotopes and involves extensive delays in
      obtaining results. A rationally designed cortisol-linker conjugate allowing high
      assay sensitivity was employed as a coating antigen in a microfluidic surface
      plasmon resonance (SPR) biosensor immunoassay for the ultrasensitive and rapid
      detection of salivary cortisol. Detection of cortisol is by competitive
      immunoassay using a secondary antibody for signal enhancement. The method
      requires no chemical extraction or complex sample pre-treatment despite high
      saliva viscosity. The cortisol assay was optimized for maximum sensitivity in
      buffer before being adapted for the salivary matrix, where it showed a limit of
      detection of 49 pg/mL. The results showed good correlation to RIA (r = 0.94). The
      biosensor assays showed an inter-assay coefficient of variation (CV) of 13.5% and
      recoveries close to 100%. The covalently immobilized sensor surface provided
      stable responses for more than 140 binding and regeneration cycles, enabling re
      use. Cortisol in saliva was detected across the physiologically relevant range
      using the SPR immunobiosensor by employing a rationally designed assay format
      including signal enhancement for maximum sensitivity. The system can handle
      saliva matrix effects by use of chemical treatment during the assay to reduce non
      specific binding to sensor surfaces. This sensor system provides an automated,
      high sensitivity analytical tool capable of yielding results in approximately 15
      min. This biosensor could potentially be used for active stress-monitoring and in
      the diagnosis of disease.

PMID- 19173067
TI  - A novel approach to correct variations in Raman spectra due to photo-bleachable
      cellular components.
AB  - Bacterial typing by Raman spectroscopy is based on small spectral differences
      that exist between strains, due to differences in their overall molecular
      composition. These strain-specific spectral differences can be obscured by
      sources of non-specific signal variance. One such source is the signal
      contribution of microbial pigments that can vary strongly in intensity. Examples
      of such pigments are carotenoids in Staphylococcus aureus, and other pigments in
      Pseudomonas aeruginosa and Mycobacterium lentiflavum. The variance in the
      intensity of these pigments greatly overshadows strain-specific differences, and
      therefore lowers spectral reproducibility and causes misclassification of
      microbial strains. Here a method is presented to determine the spectral signature
      of pigments of which the relative signal contribution decreases under laser
      irradiation; so-called photo-bleachable pigments. These signatures are used to
      eliminate signal variance caused by these pigments by means of the extended
      multiplicative scatter correction algorithm and spectral interferent subtraction.
      Application of this method increases the reproducibility of the spectra of
      microorganisms that contain such pigments to the extent that reproducible
      identification of samples at strain level is achieved.

PMID- 19173068
TI  - Differentiation of liquid analytes in gel films by permeability-modulated double
      layer chemo-chips.
AB  - A double-layer chemo-chip for the characterization of liquid analytes by rapid
      fluorimetric imaging is described. The chemo-chip consists of an array of
      polymeric micro-spots prepared on a glass slide. Each spot is composed of a thin
      indicator layer made of PVA doped with an immobilized fluorescence dye and a top
      layer polymer spot with different permeation properties. The analytes can be
      differentiated by variations in the optical response rate of the indicator dye
      after its application. Consequently, different cross-linker concentrations were
      applied using the Nano-Plotter((TM)) which formed top layers of varying
      permeability. The chemo-chips were tested with the aqueous solutions of two model
      liquids (aqueous solutions of malonic acid and phenanthroline hydrochloride). It
      was found that the transition time of response had changed considerably (up to a
      factor of about 10) depending on different local cross linking degrees. This has
      resulted in time-dependent fluorescent patterns of the fluorescence images of the
      micro-array. The response was fast and the transition times were in the range
      between a few seconds to 30 s.

PMID- 19173069
TI  - High temporal resolution coupling of low-flow push-pull perfusion to capillary
      electrophoresis for ascorbate analysis at the rat vitreoretinal interface.
AB  - A system is presented demonstrating the high-temporal resolution coupling of low
      flow push-pull perfusion sampling (LFPS) to capillary electrophoresis for the
      absorbance measurement of ascorbate at the rat vitreoretinal interface. This
      system holds all separation components at a low pressure as the means for
      withdrawing sample during LFPS. The system uses a flow-gated interface to
      directly couple the withdrawal capillary from the LFPS probe to a separation
      capillary and eliminates the need for any offline sample handling. The temporal
      resolution of the system was limited by injection time and is less than 16 s.
      This high temporal resolution was applied to the monitoring of in vivo ascorbate
      levels at the rat vitreoretinal interface. Baseline concentrations of ascorbate
      were found to be 86 microM +/- 18 microM at the vitreoretinal interface. Baseline
      concentrations matched well with those obtained for the postmortem bulk vitreous
      analysis. Upon stimulation with 145 mM K(+), a maximum increase in baseline
      values between 32-107% for n = 3 was observed. This system demonstrates the first
      in vivo temporal study of ascorbate at the rat vitreoretinal interface.

PMID- 19173071
TI  - Sandwiched sodium and half-sandwiched copper carbonyl complexes featuring
      polyfluorinated tris(triazolyl)borate [HB(3,5-(CF(3))(2)Tz)(3)](-).
AB  - Fluorinated tris(triazolyl)borate [HB(3,5-(CF(3))(2)Tz)(3)](-) (Tz = triazolyl)
      affords the isolation of [Na(THF)(6)]{[HB(3,5-(CF(3))(2)Tz)(3)](2)Na} with a
      ligand sandwiched sodium ion and a copper carbonyl complex [HB(3,5
      (CF(3))(2)Tz)(3)]CuCO with a high C-O stretching frequency.

PMID- 19173072
TI  - Structural and biological investigation of ferrocene-substituted 3-methylidene
      1,3-dihydro-2H-indol-2-ones.
AB  - The Knoevenagel condensation of 1,3-dihydro-2H-indol-2-one with ferrocene
      carboxaldehyde afforded an approximate 2:1 mixture of the geometrical isomers (E)
      and (Z)-3-ferrocenylmethylidene-1,3-dihydro-2H-indol-2-one respectively in an
      overall 67% yield; the air and solution-stable isomers were readily separated by
      preparative thin layer chromatography and their structures were unequivocally
      elucidated in solution, by (1)H NMR spectroscopy, and in the solid phase, by X
      ray crystallography; both isomers of displayed in vitro toxicity against B16
      melanoma and Vero cell lines in the micromolar range and inhibited the kinase
      VEGFR-2 with IC(50) values of ca. 200 nM.

PMID- 19173070
TI  - myo-Inositol oxygenase: a radical new pathway for O(2) and C-H activation at a
      nonheme diiron cluster.
AB  - The enzyme myo-inositol oxygenase (MIOX) catalyzes conversion of myo-inositol
      (cyclohexan-1,2,3,5/4,6-hexa-ol or MI) to d-glucuronate (DG), initiating the only
      known pathway in humans for catabolism of the carbon skeleton of cell-signaling
      inositol (poly)phosphates and phosphoinositides. Recent kinetic, spectroscopic
      and crystallographic studies have shown that the enzyme activates its substrates,
      MI and O(2), at a carboxylate-bridged nonheme diiron(ii/iii) cluster, making it
      the first of many known nonheme diiron oxygenases to employ the mixed-valent form
      of its cofactor. Evidence suggests that: (1) the Fe(iii) site coordinates MI via
      its C1 and C6 hydroxyl groups; (2) the Fe(ii) site reversibly coordinates O(2) to
      produce a superoxo-diiron(iii/iii) intermediate; and (3) the pendant oxygen atom
      of the superoxide ligand abstracts hydrogen from C1 to initiate the unique C-C
      bond-cleaving, four-electron oxidation reaction. This review recounts the studies
      leading to the recognition of the novel cofactor requirement and catalytic
      mechanism of MIOX and forecasts how remaining gaps in our understanding might be
      filled by additional experiments.

PMID- 19173073
TI  - Unprecedented double migratory insertion of phenyl isocyanide into
      cyclopentadienyl C-H bonds.
AB  - The reaction of [(eta(5)-C(5)H(5))Cu(CNPh)] with phenyl-isocyanide results in an
      unprecedented double migratory insertion into two sp(2) C-H bonds of a eta(5)
      coordinated cyclopentadienyl group, and formation of the 6-aminofulvene-2
      aldimine complexes [(CNPh)Cu{kappa(2)-N,N-C(5)H(3)-1,2-(CHNPh)(2)}] and
      [(CNPh)(2)Cu{kappa(2)-N,N-C(5)H(3)-1,2-(CHNPh)(2)}], respectively, both of which
      have been structurally characterised.

PMID- 19173074
TI  - Unusual formation of a [NiSFe(2)(CO)(6)] cluster: a structural model for the
      inactive form of [NiFe] hydrogenase.
AB  - The synthesis and characterisation of the trinuclear Ni-Fe complex
      [Ni(L(2))SFe(2)(CO)(6)] (1) formed from the reaction of [Ni(L(1))] with
      Fe(3)(CO)(12) is described. The single-crystal X-ray structure of 1 shows Ni(ii)
      bound to three thioether R(2)-S donors and bridged by a sulfide (S(2-)) group to
      two Fe(CO)(3) units. undergoes a reversible one-electron reduction process at
      E(1/2) = -1.62 V vs. Fc(+)/Fc to generate 1 (-), which has been characterised by
      UV-vis and IR spectroelectrochemistry and by EPR spectroscopy. DFT calculations
      on 1and 1 (-) reveal electronic structures that are delocalised across the
      NiFe(2) core. The SOMO in 1 (-) possesses Ni-Fe and Fe-Fe anti-bonding character
      and lies approximately in the plane defined by the equilateral triangle of Ni and
      Fe atoms. It possesses d-orbital contributions of 18.5, 15.0 and 19.8% for the
      Ni(1), Fe(1) and Fe(2) atoms, respectively. The Ni-S(sulfide) bond length in 1
      [2.1654(7) A] is identical to that for the bridging sulfide found in the oxidised
      inactive form of the [NiFe] hydrogenase from D. vulgaris (2.16 A). Thus, 1
      provides a useful comparison for biological [NiFe] centres bridged by sulfide
      donors.

PMID- 19173075
TI  - Binding of [Pt(1C3)(dien)](2+) to the duplex DNA oligonucleotide 5'-d(TGGCCA)-3':
      the effect of an appended positive charge on the orientation and location of
      anthraquinone intercalation.
AB  - The binding of a platinum intercalator complex [Pt(1C3)(dien)](2+) (1C3 = 1-[(3
      aminopropyl)amino]-anthracene-9,10-dione, dien = 3-azapentane-1,5-diamine) to DNA
      and to the self-complementary oligonucleotide 5'-d(TGGCCA)-3' has been
      investigated by UV-visible spectrophotometry and 2D NMR spectroscopy,
      respectively. The uncomplexed anthraquinone, 1C3, has an apparent DNA binding
      constant of 1.4 x 10(4), similar to that of ethidium bromide. Addition of the
      coordinatively saturated {Pt(dien)} moiety increases the binding constant to 3.7
      x 10(5) M(-1), showing the effect of the increased positive charge introduced by
      this moiety. Multiple binding modes are evident from the lack of isosbestic
      points in the titration spectra and the non-linear nature of the half-reciprocal
      plot used to calculate the binding constant. [Pt(1C3)(dien)](2+) forms a 2 : 1
      adduct with 5'-d(TGGCCA)-3' and is shown by 2D NMR to intercalate primarily in
      the TG:CA base pairs at the ends of the oligonucleotide with the side chain and
      {Pt(dien)} situated in the minor groove.

PMID- 19173076
TI  - Combination of POMs and deliberately designed macrocations: a rational approach
      for synthesis of POM-pillared metal-organic framework.
AB  - Two POM-pillared 3D porous compounds,
      [Cu(I)Cu(II)(Cu(II)fcz)(2)(H(2)O)(5)(PMo(VI)(10)Mo(V)(2)O(40))].6H(2)O () and
      [Cu(I)(2)(Cu(II)fcz)(2)(H(2)O)(2)(PMo(VI)(8)V(V)(3)V(IV)(3)O(42))].6H(2)O ()
      (Hfcz = fluconazole, (1-(2,4-difluorophenyl)-1,1-bis[(1H-1,2,4-triazol-1
      yl)methyl]benzyl alcohol) have been constructed based on different polyanions,
      (Cufcz)(2)(2+) macrocations and copper cations by the hydrothermal method. The
      (Cufcz)(2)(2+) macrocations link Cu cations to generate a 2D wavelike cationic
      sheet. Then the POM anions act as pillars to the cationic sheet to form different
      POM-pillared 3D frameworks. In compound 2 , the polyanion exhibits a rare
      coordination mode and acts as a penta-dentate ligand, which acts as to pillars to
      the cationic sheet to form an unprecedented 3D (3,4,5,6)-connected open framework
      with
      (3.6.7)(3(2).6.7(3))(3(3).4.6(2).7(3).8)(3(4).4(2).6(2).7(6).8)(3(2).6(2).7(6).8(
      ).10) topology. In compound , polyanions covalently link cationic sheets to
      extend to an unusual 3D (3,4,6)-connected framework with the
      (5(2).6)(5(2).6(2).7.9)(5(4).6(4).7(4).9(3)) topology. To the best of our
      knowledge, it is the first time that POM-pillared 3D metal-organic frameworks
      have been realized by combining POMs with deliberately designed macrocations and
      transition-metal ions, using a rational approach for synthesis of POM-based open
      metal-organic frameworks. In addition, the electrochemical behaviors of compounds
      1 and 2 have been investigated.

PMID- 19173077
TI  - Rigidity effect of the dithioether spacer on the size of the luminescent cluster
      (Cu(2)I(2))(n) (n = 2, 3) in their coordination polymers.
AB  - Treatment of CuI with the flexible PhS(CH(2))(4)SPh dithioether ligand in MeCN
      solution affords the strongly luminescent metal-organic 2D coordination polymer
      [Cu(4)I(4){mu-PhS(CH(2))(4)SPh}(2)](n) (). The interpenetrated 2D network of is
      built upon by Cu(4)(mu(3)-I)(4) cubane-like clusters as secondary building units
      (SBUs), which are interconnected via bridging 1,4-bis(phenylthio)butane ligands.
      In contrast, the auto-assembly reaction of the unsaturated semi-flexible
      PhSCH(2)C[triple bond, length as m-dash]CCH(2)SPh ligand with CuI results in
      formation of the 3D metallopolymer [(Cu(6)I(6)){mu-PhSCH(2)C[triple bond, length
      as m-dash]CCH(2)SPh}(3)](n) (). The SBUs of luminescent consist of discrete
      Cu(6)(mu(3)-I)(6) hexagon prisms, which are coordinated with bridging 1,4
      bis(phenythio)butyne ligands via Cu-S bonds. Contrary to the other rare
      literature-known examples of metallopolymers incorporating Cu(6)X(6) SBUs as
      connecting nodes, the CuCu interactions of [2.8484(6) A] are markedly shorter,
      being close to the sum of the Van der Waals radii of two Cu atoms ( approximately
      2.8 A). The photophysics of these compounds, which exhibit reversible
      luminescence thermochromism, has been investigated in detail. The solid-state
      luminescence spectra of and feature at room temperature intense emissions around
      560 and 555 nm, respectively. The luminescence properties of the unusual
      Cu(6)(mu(3)-I)(6) hexagon prism motif are rationalized by means of DFT and TDDFT
      computations.

PMID- 19173078
TI  - Activation and cleavage of the N-O bond in dinuclear mixed-metal nitrosyl systems
      and comparative analysis of carbon monoxide, dinitrogen, and nitric oxide
      activation.
AB  - The activation and scission of the N-O bond in nitric oxide using dinuclear mixed
      metal species, comprising transition elements with d(3) and d(2) configurations
      and trisamide ligand systems, have been investigated by means of density
      functional calculations. The [Cr(iii)-V(iii)] system is analyzed in detail and,
      for comparative purposes, the [Mo(iii)-Nb(iii)], [W(iii)-Ta(iii)], and (mixed
      row) [Mo(iii)-V(iii)] systems are also considered. The overall reaction and
      individual intermediate steps are favourable for all systems, including the case
      where first row (Cr and V) metals are exclusively involved, a result that has not
      been observed for the related dinitrogen and carbon monoxide systems. In contrast
      to the cleavage of dinitrogen by three-coordinate Mo amide complexes where the
      dinuclear intermediate possesses a linear [Mo-NN-Mo] core, the [M-NO-M'] core
      must undergo significant bending in order to stabilize the dinuclear species
      sufficiently for the reaction to proceed beyond the formation of the nitrosyl
      encounter complex. A comparative bonding analysis of nitric oxide, dinitrogen and
      carbon monoxide activation is also presented. The overall results indicate that
      the pi interactions are the dominant factor in the bonding across the [M-L(1)L(2)
      M'] (L(1)L(2) = N-O, N-N, C-O) moiety and, consequently, the activation of the
      L(1)-L(2) bond. These trends arise from the fact that the energy gaps between the
      pi orbitals on the metal and small molecule fragments are much more favourable
      than for the corresponding sigma orbitals. The pi energy gaps decrease in the
      order [NO < N(2) < CO] and consequently, for each individual pi orbital
      interaction, the back donation between the metal and small molecule increases in
      the order [CO < N(2) < NO]. These results are in accord with previous findings
      suggesting that optimization of the pi interactions plays a central role in
      increasing the ability of these transition metal systems to activate and cleave
      small molecule bonds.

PMID- 19173079
TI  - The comparison of fac and mer ruthenium(ii) trischelate complexes in anion
      binding.
AB  - The synthesis of three new homoleptic trischelate ruthenium(ii) complexes bearing
      new 2,2'-bipyridine ligands, 5,5'-dibenzylamido-2,2'-bipyridine () and 5
      benzylamido-2,2'-bipyridine (L1) has been achieved. In the case of
      [Ru(L2)(3)](2+), the mer and fac isomers have been separated. (1)H NMR
      spectroscopic anion binding studies indicate that the two C(3)-symmetric pockets
      provided by [Ru(L1)(3)](2+) is conducive to receive a range of anions, although
      this is not readily reflected in the photophysical behaviour. The fac-isomer of
      [Ru(L2)(3)](2+) does appear to have an enhancement in the binding interactions
      over the mer form with dihydrogenphosphate salts, although the difference is much
      less marked with the spherical chloride ions. From X-ray crystallographic
      evidence, the ability to hold water in the "anion" binding cleft can inhibit the
      strength of the interactions with anions, giving rise to the observed selectivity
      for directional oxoanions such as dihydrogen phosphate.

PMID- 19173080
TI  - Structure and magnetism of decanuclear and octadecanuclear manganese(II/III)
      triethanolamine clusters.
AB  - Two new potential single molecule magnets
      [Mn(10)O(3)(O(2)CCH(3))(6)(tea)(teaH)(3)(teaH(2))(3)][NO(3)](2).3H(2)O (1) and
      [Mn(18)(N(3))(12)O(12)(tea)(2)(teaH)(4)(OMe)(MeOH)].2MeOH.H(2)O.Et(2)O (2) have
      been synthesised using manganese(II) nitrate, the tripodal ligand triethanolamine
      (teaH(3)) and co-ligands such as acetate for 1 and azide for 2. Both compounds
      are mixed-valent with 1 consisting of 4 Mn(II) and 6 Mn(III) ions and 2
      consisting of 3 Mn(II) and 15 Mn(III) ions. Complex 1 has a near planar
      Mn(7)(II/III) disc-like core with 3 Mn(II) ions positioned on the periphery of
      the disc, forming a star-like geometry. Complex 2 contains a hexa-capped
      truncated tetrahedral core. Variable temperature DC magnetic susceptibility data
      collected in 2, 1, 0.1 and 0.01 T fields, and in the 2-300 K temperature range,
      for 1 and 2, indicate a large ground spin-state for both compounds. Using a new
      approach to calculating the DC Mvs. H isotherms (or isofield Mvs. H/T curves) by
      means of the thermal population of Zeeman levels generated from a group of
      closely spaced S states (within 9 cm(-1) of ground), the ground S of 1 is 10. The
      ZFS term, D, is close to zero. For 2 , the magnetisation isotherms, and low
      temperature susceptibilities, point to a ground state spin of (21)/(2) with many
      closely spaced spin states (probably from (17)/(2) to (35)/(2)) close in energy,
      the lowest Zeeman level energies of which change as the field increases. AC
      magnetic susceptibility data show frequency-dependent out-of-phase signals
      indicating both clusters are possibly single molecule magnets. Extrapolation of
      the in-phase component, chi'(M)T, to 0 K suggests spin ground state of S = 10 for
      1 and (21)/(2) for 2 , in agreement with the DC data.

PMID- 19173081
TI  - Synthesis and properties of a novel tripodal bipyridyl ligand tb-carbinol and its
      Ru(II)-Re(I) trimetallic complexes: investigation of multimetallic artificial
      systems for photocatalytic CO(2) reduction.
AB  - A novel tripodal ligand, tris[(4'-methyl-2,2'-bipyridin-4-yl)methyl]carbinol (tb
      carbinol) and its homonuclear and heteronuclear Ru(II)-Re(I) complexes have been
      synthesized and characterized by NMR spectroscopy, elemental analysis, and mass
      spectroscopy. The spectroscopic, electrochemical and photocatalytic properties of
      the Ru(II)-Re(I) complexes have been investigated. In these supramolecular
      complexes with tb-carbinol as a bridging ligand, the intramolecular interaction
      among the terminal metal centers is very weak. In the cases of Ru(II) and Re(I)
      heteronuclear systems, when the Re(I) moieties are excited, the emission from the
      Re(I) moiety is efficiently quenched and the intensity of the emission from the
      Ru(II) moiety increases. The rate constant of energy transfer from Re(I) moieties
      to Ru(II) unit in RuRe(2) is 1.7 x 10(8) s(-1). From the point of view of the
      free energy change, the intramolecular electron transfer from the Ru(II) moiety
      to the Re(I) moiety could proceed smoothly in the ground state. Both of Ru(2)Re
      and RuRe(2) show excellent photocatalytic activities to the CO(2) reduction.
      RuRe(2) exhibits a turnover number of 190 for CO formation compared with 89 from
      the model complexes system after 16 h of irradiation (TN(CO) calculated based on
      Ru(II) moiety concentration). Ru(2)Re shows a higher turnover number than the
      model complexes system, 110 compared with 55 from the model system (TN(CO)
      calculated based on Re(I) moiety concentration). The bridging ligand of Ru(II)
      Re(I) heteronuclear tripodal systems, tb-carbinol, plays an important role in
      converting radiant energy to chemical energy in the form of CO from CO(2).
      Enhancement of the photocatalytic response to light in the visible region has
      been achieved by fabricating supramolecular systems featuring covalently linked
      Ru(II) and Re(I) moieties.

PMID- 19173082
TI  - Synthesis and characterization of a series of manganese phosphonate complexes
      with various valences and nuclearity.
AB  - A series of new manganese phosphonate clusters with unprecedented topologies,
      [Mn(20)Na(4)O(12)(t-BuPO(3))(12)(O(2)CMe)(16)(H(2)O)(12)].5H(2)O (),
      [Mn(15)O(6)(MePO(3))(2)(MeCOO)(18)(H(2)O)(12)][MePO(3)H](2).12H(2)O (), and [Mn(t
      BuPO(3)H)(2)(phen)(2)].MeCOOH () have been synthesized and characterized. The
      core of is composed of two folded "butterfly-like" [Mn(4)(mu(3)-O)(2)] units and
      two trigonal prism [Mn(6)O(6)] units connected by four mu(3)-O, resulting in a
      twisted oval of twenty homovalent manganese(iii) ions. The pentadecanuclear core
      of complex is mixed-valent, containing six Mn(III) and nine Mn(II) ions and
      features six mu(4)-O and two capping MePO(3)(2-) anions adopting the binding mode
      [6.222], forming a rudder-like cage structure with a chiral D(3) symmetry.
      Compound is a manganese(ii) phosphonate and features a 1D chain configuration
      packed by hydrogen bonds and pi-pi stacking interactions. Magnetic susceptibility
      measurements reveal that compounds 1, 2 , and 3 display antiferromagnetic
      interactions between the adjacent manganese ions, while the in-phase signal
      chi'(M)T and out-of-phase signal chi''(M) of complex 1 exhibit frequency
      dependence below approximately 3 K, but no frequency-dependence is observed in
      the ac signals of complex 2.

PMID- 19173083
TI  - Employment of methyl 2-pyridyl ketone oxime in manganese non-carboxylate
      chemistry: Mn(II)(2)Mn(IV) and Mn(II)(2)Mn(III)(6) complexes.
AB  - The employment of the anion of methyl 2-pyridyl ketone oxime (mpko(-)) as a
      tridentate chelating/bridging ligand in manganese chemistry is described. The
      inorganic anion (Br(-), ClO(4)(-)) used in the reaction affects the identity of
      the product. The reaction of MnBr(2) and one equivalent of mpkoH in the presence
      of a base affords [Mn(3)(OMe)(2)(mpko)(4)Br(2)] (3), which is mixed-valence
      (2Mn(II), Mn(IV)). The central Mn(IV) atom in each of the two,
      crystallographically independent, centrosymmetric molecules is coordinated by
      four oximate oxygen atoms belonging to the eta(1):eta(1):eta(1):mu mpko(-)
      ligands, and two eta(1):mu MeO(-) groups, while six coordination at each terminal
      Mn(II) atom is completed by four nitrogen atoms belonging to the 'chelating' part
      of two mpko(-) ligands, and one Br(-) ion. The Mn(II) atoms have trigonal
      prismatic coordination geometry. The reaction of Mn(ClO(4))(2).6H(2)O, mpkoH and
      OH(-) (1:2:1) in MeOH gives [Mn(8)O(4)(OMe)(mpko)(9)(mpkoH)](ClO(4))(4) (4),
      which is also mixed-valence (2Mn(II), 6Mn(III)) and possesses the novel
      [Mn(8)(mu(3)-O)(4)(mu-OMe)(mu-OR'')(2)](11+) core. The latter possesses a U
      shaped sequence of four fused {Mn(II)Mn(III)(2)(mu(3)-O)}(6+) triangular units,
      with a Mn(III)-Mn(III) edge being shared between the central triangles. Variable
      temperature, solid-state dc and ac magnetic susceptibility studies were carried
      out on complexes 3 and 4 . The dc susceptibility data for 3 in the 5.0-300 K
      range have been fit to a model with two J values, revealing weak ferromagnetic
      Mn(II)Mn(IV) (J = +3.4 cm(-1)) and Mn(II)Mn(II) (J' = +0.3 cm(-1)) exchange
      interactions. Fitting of the magnetization vs. H/T data by matrix diagonalization
      and including only axial anisotropy (ZFS, D) gave ground state spin (S) and D
      values of S = 13/2, D = +0.17 cm(-1) for and S = 3, D = -0.09 cm(-1) for 4 . The
      combined work demonstrates the usefulness of mpko(-) in the preparation of
      interesting Mn clusters, without requiring the co-presence of carboxylate
      ligands.

PMID- 19173084
TI  - Cationic and neutral Ni(II) complexes containing a non-innocent PNP ligand:
      formation of alkyl and thiolate species.
AB  - The synthesis and characterization of a series of cationic and neutral Ni
      complexes with the non-innocent PNP(tBu) pincer ligand is discussed. Starting
      with the dicationic complex , [Ni(PNP(tBu))(NCMe)](BF(4))(2), a small series of
      dicationic and monocationic Ni(II) complexes has been prepared. Substitution with
      tert-butyl isocyanide and azide occurs readily in MeCN solution. IR spectroscopy
      provided a practical handle to access the formal valence state of the ligand. For
      the mono- and dicationic tert-butyl isocyanide species and the main vibrational
      bands in the IR spectra were reproduced quantitatively by DFT theoretical
      calculations, showing good agreement with the experimentally observed Deltanu
      upon dearomatization of the PNP(tBu) backbone. Using a selective dearomatization
      reprotonation methodology the mononuclear Ni-thiolate species and are cleanly
      generated and their structures have been determined by X-ray crystal structure
      determination. Alternatively, starting from the monocationic species
      [Ni(PNP(tBu))Cl]BF(4), neutral alkyl derivatives are easily available in a two
      step procedure, and these species have been spectroscopically characterized.

PMID- 19173085
TI  - DNA binding and oxidative DNA cleavage activity of (mu-oxo)diiron(iii) complexes
      in visible light.
AB  - Four (mu-oxo)diiron(iii) complexes [Fe(2)(mu-O)(H(2)O)(2)B(4)](ClO(4))(4) ( and )
      and [Fe(2)(mu-O)(mu-O(2)CMe)B(4)](ClO(4))(3) ( and ), where B = 1,10
      phenanthroline (phen) and dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), are prepared
      and their DNA binding and cleavage activity studied. The complexes show DNA
      binding propensity giving K(b) values of 3.6-9.3 x 10(4) M(-1). The viscosity and
      DNA melting data suggest a surface and/or groove binding nature of the complexes
      to calf thymus (CT) DNA. The DNA binding data obtained from isothermal
      calorimetric study indicate two binding modes involving surface aggregation
      and/or partial intercalation of the phenanthroline bases to CT DNA. All the
      complexes show chemical nuclease activity in the presence of 3-mercaptopropionic
      acid as a reducing agent following a mechanistic pathway that involves formation
      of superoxide and hydroxyl radicals. Photoirradiation of pUC19 DNA at 365 nm in
      the presence of 1-4 show that the complexes, barring 1 , are efficient
      photocleavers of supercoiled DNA to its nicked circular form. Complexes 2-4
      display photocleavage activity in visible light of different wavelengths.
      Complexes 3 and 4 exhibit significant DNA cleavage activity in red light of 633
      nm, the wavelength known for the activity of the photodynamic therapeutic drug
      Photofrin. The mechanistic study using various additives suggests a minor groove
      binding nature of the complexes with the formation of singlet oxygen from the
      quinoxaline moiety of dpq and hydroxyl radical from photodecarboxylation of the
      acetate ligand as the reactive oxygen species.

PMID- 19173086
TI  - Photoinduced linkage isomerism of {RuNO}(6) complexes with bioligands and related
      chelators.
AB  - Five novel complexes containing the {RuNO}(6) fragment and the anions derived
      from l-histidine (l-his), rac-3-amino-alanine (rac-dap), kojic acid (koj),
      methyliminodiacetic acid (mida), and thiodiacetic acid (tda) have been
      synthesised and characterised by single-crystal X-ray diffraction analysis, mass
      spectrometry, spectroscopic methods (NMR, UV-vis, IR) and elemental analysis. In
      the irradiated complexes, [Ru(NO)Cl(2)(l-his)] (1), [Ru(NO)Cl(2)(rac-dap)] (2),
      K[Ru(NO)Cl(3)(koj)] (3), K[Ru(NO)Cl(2)(mida)].(1/2)H(2)O (4), and
      K[Ru(NO)Cl(2)(tda)].H(2)O (5), the existence of the photoinduced long-lived
      metastable isonitrosyl state S1 and/or the side-on-bonded S2 state were detected
      by differential scanning calorimetry (DSC) and/or IR spectroscopy. For all
      complexes 1-5 full geometry optimisation, frequency analysis and calculation of
      the isotropic magnetic shielding tensors have been conducted in the framework of
      DFT theory.

PMID- 19173087
TI  - Metal and ligand substitution of the aluminium tris-pyridyl ligands [RAl(2
      py')(3)](-) (R = Et, (n)Bu, (s)Bu, (t)Bu; 2-py' = 2-pyridyl, 3-methyl-2-pyridyl,
      5-methyl-2-pyridyl, 6-methyl-2-pyridyl).
AB  - A series of tris-pyridyl complexes [RAl(2-py)(3)]Li.thf [2-py = 2-pyridyl; R = Et
      (1); (n)Bu (2); (s)Bu (3), (t)Bu (4)] were prepared by the sequential reaction of
      AlCl(3) with RLi then 2-Li-py in thf. The related complexes [MeAl{2-(3
      Me)py}(3)]Li(mu-Br)Li(thf)(3) (5), [MeAl{2-(5-Me)py}(3)]Li.thf (6) and [MeAl{2-(6
      Me)py}(3)]Li.thf (7) are obtained similarly from MeAlCl(2) and the appropriate
      lithio-pyridine (2-Li-py'). The synthetic approaches used provide the means for
      extensive elaboration of the [RAl(2-py')(3)](-) ligand frameworks, and
      potentially broad access to a large range of new anionic tris-pyridyl ligands of
      this type. Fundamental insights into how the ligand bites and coordination
      environments offered are modified by substituents at the Al bridgehead and
      pyridyl rings are given by the solid-state structures of 1-7 .

PMID- 19173088
TI  - Partial double bond character in chalcogen compounds of stanna-closo
      dodecaborate.
AB  - The following chalcogen compounds of stanna-closo-dodecaborate were synthesized
      and characterized: the tetrameric oxide [(O-SnB(11)H(11))(4)](8-) from the
      reaction with hydrogen peroxide and the sulfide and selenide [S-SnB(11)H(11)](2
      ), [Se-SnB(11)H(11)](2-) from the reaction with elemental sulfur and selenium,
      respectively. The stannaborate derivatives were characterized by (119)Sn
      Mossbauer spectroscopy and single crystal structural analysis. The character of
      the bond between the tin and group 16 elements was studied extensively by using
      quantum chemical methods.

PMID- 19173089
TI  - Systems for the management of respiratory disease in primary care--an
      international series: South Africa.
AB  - INTRODUCTION: Progress to democracy in South Africa in 1994 was followed by the
      adoption of a primary health care approach with free access for all. State health
      facilities serve 80% of the population, and a private sector comprising general
      practitioners, specialists and private hospitals, serves the remainder. NATIONAL
      POLICIES AND MODELS: There are national prescribing guidelines for common
      diseases, and these specify the medicines on the Essential Drugs List that are
      available at primary care facilities for respiratory diseases including asthma,
      COPD, pneumonia and tuberculosis. EPIDEMIOLOGY: Asthma prevalence is average
      among children (13%) but morbidity is high. COPD rates are high owing to
      concurrent risk factors of smoking (in both men and women), occupational
      exposures, biomass fuel use and previous lung infections including tuberculosis.
      Tuberculosis and HIV are rampant, and together with pneumococcal co-infection
      account for considerable mortality. ACCESS TO CARE: Primary care facilities are
      within reach of most communities, but major barriers to care include loss of
      income, waiting times in clinics, cost of transportation, and inconvenient hours.
      FACILITIES AVAILABLE: The country is divided into districts each served by a
      hospital, several community health centres and many fixed or mobile clinics. The
      latter provide predominantly nurse-led care by nurse practitioners with
      additional qualifications. Some clinics and most community health centres are
      served by doctors. Referrals are made to secondary and tertiary hospitals served
      by specialists. FUTURE: Innovations to address staff shortages include the
      creation of the specialty of family medicine for physicians and development of
      the clinical associate who is trained to perform a limited clinical role, as well
      as in-service on-site training of nurses through programmes of integrated care
      for infectious and chronic diseases. There is an urgent need to address low staff
      morale and medical migration resulting from a decade of poor leadership and AIDS
      denialism. CONCLUSIONS: The structures and policies for primary care in South
      Africa provide some grounds for optimism that services may begin to match the
      promise of quality care for all, but the burden of disease and resource
      constraints - particularly in terms of qualified personnel - mitigate against an
      early delivery of this promise.

PMID- 19173090
TI  - Are executive control functions related to autism symptoms in high-functioning
      children?
AB  - BACKGROUND: Linking autism symptoms to cognitive abilities can expand phenotypic
      descriptions and facilitate investigations into the etiology and treatment of
      this multiplex disorder. Executive dysfunction is one of several potential
      cognitive phenotypes in autism. METHOD: Archival clinical data on 89 children
      diagnosed with Autism Spectrum Disorders and administered a large
      neuropsychological battery were evaluated for relationships between executive
      functioning and autism symptoms. RESULTS: Significant relationships between both
      laboratory tasks and behavior rating scales of executive functions and autism
      symptoms were identified. Multiple regression analyses revealed that measures of
      semantic fluency, divided auditory attention, and behavioral regulation were
      significantly correlated with autism symptoms, even after accounting for the
      variance from correlated "nuisance variables," such as vocabulary and age.
      CONCLUSIONS: Executive dysfunction is related to all three clusters of behavioral
      symptoms in Autism Spectrum Disorders.

PMID- 19173091
TI  - A suspicion of chikungunya leading to a diagnosis of angioimmunoblastic T-cell
      lymphoma.

PMID- 19173094
TI  - Evidence-based imaging in trauma radiology: where we are and how to move forward.
AB  - Evidence-based imaging is an important tool for the determination of which
      subjects should undergo imaging and what imaging approach should be applied. This
      paper includes a summary of the methods of evidence-based imaging, including
      formulation of a clinically relevant question, searching the medical literature,
      critically analyzing the data, summarizing the evidence, and applying the
      evidence to practice. Application of the many validated clinical prediction rules
      to trauma imaging is also discussed. In addition, the challenges of evidence
      based imaging and the needs for future research are detailed.

PMID- 19173092
TI  - An ER activity profile including ER, PR, Bcl-2 and IGF-IR may have potential as
      selection criterion for letrozole or tamoxifen treatment of patients with
      advanced breast cancer.
AB  - INTRODUCTION: The purpose of this study was to evaluate the association between
      response at recurrence to letrozole versus tamoxifen and the expression of
      estrogen regulated proteins individually and combined in an "ER activity profile"
      in primary tumor tissue. Our hypothesis is that letrozole may be more effective
      than tamoxifen for treatment of tumors with high intratumoral estrogen content,
      whereas tamoxifen may be more efficient for treatment of tumors with high levels
      of the estrogen receptor (ER) and low intratumoral estrogen content. MATERIALS
      AND METHODS: For this study, we produced tissue microarrays from formalin fixed
      paraffin embedded primary tumor material from a subgroup of patients (9.4%), who
      have participated in the international, randomized, phase III clinical trial PO25
      comparing letrozole with tamoxifen in 907 patients with advanced breast cancer.
      The expression levels of ER, the progesterone receptor (PR), the anti-apoptotic
      protein Bcl-2 and the Insulin like Growth Factor Receptor I (IGF-IR) were
      determined by semi-quantitative immunohistochemistry. RESULTS: Response to
      letrozole and tamoxifen treatment, measured as time to progression (TTP), was
      independent of primary tumor expression level of ER, Bcl-2 and IGF-IR. However,
      high expression of PR as well as high expression of three different ER activity
      profiles; ER/PR/Bcl-2, ER/PR/IGF-IR and ER/PR/Bcl-2/IGF-IR identified letrozole
      treated patients with significantly longer TTP. The ER activity profile including
      ER, PR, Bcl-2 and IGF-IR showed a trend towards being a selection criterion for
      letrozole versus tamoxifen therapy. DISCUSSION: This small sub-study supports our
      hypothesis that letrozole is superior to tamoxifen primarily in patients
      expressing high levels of estrogen regulated proteins in the primary tumor
      tissue. Furthermore, it seems that the "ER activity profile" with high PR, IGF-IR
      and Bcl-2 is a promising selection criterion, regarding prediction of response to
      letrozole versus tamoxifen.

PMID- 19173095
TI  - Volume-dependent overestimation of spontaneous intracerebral hematoma volume by
      the ABC/2 formula.
AB  - BACKGROUND: Although the ABC/2 formula has been widely used to estimate the
      volume of intracerebral hematoma (ICH), the formula tends to overestimate
      hematoma volume. The volume-related imprecision of the ABC/2 formula has not been
      documented quantitatively. PURPOSE: To investigate the volume-dependent
      overestimation of the ABC/2 formula by comparing it with computer-assisted
      volumetric analysis (CAVA). MATERIAL AND METHODS: Forty patients who had suffered
      spontaneous ICH and who had undergone non-enhanced brain computed tomography
      scans were enrolled in this study. The ICH volume was estimated based on the
      ABC/2 formula and also calculated by CAVA. Based on the ICH volume calculated by
      the CAVA method, the patients were divided into three groups: group 1 consisted
      of 17 patients with an ICH volume of less than 20 ml; group 2 comprised 13
      patients with an ICH volume of 20 to 40 ml; and group 3 was composed of 10
      patients with an ICH volume larger than 40 ml. RESULTS: The mean estimated
      hematoma volume was 43.6 ml when using the ABC/2 formula, compared with 33.8 ml
      when using the CAVA method. The mean estimated difference was 1.3 ml, 4.4 ml, and
      31.4 ml for groups 1, 2, and 3, respectively, corresponding to an estimation
      error of 9.9%, 16.7%, and 37.1% by the ABC/2 formula (P<0.05). CONCLUSION: The
      ABC/2 formula significantly overestimates the volume of ICH. A positive
      association between the estimation error and the volume of ICH is demonstrated.

PMID- 19173096
TI  - Fractures of the fifth metacarpal.
AB  - BACKGROUND: The literature is limited concerning the epidemiological issues of
      fracture in the fifth metacarpal bone. PURPOSE: To explore the incidence and
      types of this fracture, and how the fracture is related to age, gender, trauma
      mechanism, and at what day of the week the causing trauma occurred. MATERIAL AND
      METHODS: All hand fractures registered at the Department of Radiology, Buskerud
      Hospital, Norway, in the period between 2004 and 2006 were reviewed. RESULTS: Of
      1475 hand fractures, 271 (18.4%) were located in the fifth metacarpal bone. In
      130 of these cases (121 male, nine female), the trauma had occurred through
      aggression, such as a fistfight or from punching a hard object. The majority of
      fractures were located in the neck of the metacarpal bone (boxer's fracture). The
      median age of this group was 22 (7-51) years. Concerning the time of trauma,
      there was a significant peak during weekends (95 patients). One hundred forty-one
      of the fifth metacarpal fractures were caused by accidental trauma (99 males, 42
      females). In this group, the fractures were located approximately equally in the
      subcapital, diaphyseal, and basal part of the metacarpal. The median age was 34
      (2-90) years. The accidental traumas occurred about as often during the weekdays
      as during the weekend. CONCLUSION: Of all hand fractures, fractures of the fifth
      metacarpal bone are the most common. There are as many aggression-related
      fractures as accidental fractures in the fifth metacarpal bone. When the fracture
      is caused by aggression, the typical patient is a young male sustaining fracture
      during the weekend.

PMID- 19173097
TI  - Retention of a model pathogen in a porous media biofilm.
AB  - The inadvertent or the deliberate introduction of pathogens into drinking water
      can lead to public health consequences. Distribution system sampling strategies
      are needed to provide information on the identity, source and fate of the
      introduced pathogens. Porous media biofilm reactors conditioned with undefined
      drinking water biofilms were tested for their ability to immobilize Escherichia
      coli 0157:H7. Biofilms were established by applying continuous flow of
      biologically activated carbon treated water with natural microflora and
      supplemented nutrient solution (0.5 mg l(-1) C) for 2 or 3 weeks. Control
      reactors were clean and were not colonized with biofilm. All reactors were
      injected with slug doses of approximately 1 x 10(9) cfu E. coli O157:H7. On the
      basis of the plate count enumeration of the introduced pathogen, reactors pre
      colonized for 2 or 3 weeks retained significantly more cells (0.75 and 9.37% of
      the introduced spike dose, respectively) compared with uncolonized control
      reactors (0.22%). Compared with cultivation, microscopic direct counts and
      quantitative PCR suggested significantly higher and lower numbers of pathogens,
      respectively. Plate counts were thus considered as the method of choice for
      pathogen enumeration in this study. In addition to providing general insights
      into interactions between pathogens and drinking water biofilms, the study
      concluded that engineered biofilm systems may be considered as a device to
      capture pathogens from the bulk flow for monitoring purposes.

PMID- 19173098
TI  - In search of sexual pleasure and fidelity: vaginal practices in KwaZulu-Natal,
      South Africa.
AB  - Vaginal practices, such as intra-vaginal cleansing, drying and tightening, are
      suspected of placing women at higher risk of acquiring HIV and STIs. Yet, there
      is limited understanding of what these practices entail, what motivates women to
      undertake them and what their socio-cultural and historical meanings are. This
      paper explores the range of vaginal practices used by women in KwaZulu-Natal,
      South Africa and locates these within the context of local patterns of migration
      and understandings of sexual health and pleasure. Study activities took place at
      an urban and rural site employing qualitative research techniques: semi
      structured interviewing and an additional ethnographic component in the rural
      site. Vaginal practices were believed to be ubiquitous and a wide range of
      substances and procedures were described. Strong motivations for vaginal
      practices included women's desire to enhance men's sexual pleasure, ensure men's
      fidelity and exercise agency and control in their relationships. The common use
      of traditional medicines in this quest to maintain stable relationships and
      affect the course of love, suggests a complexity that cannot be captured by
      simple terms like 'dry sex'. We argue instead that any interventions to change
      women's reliance on vaginal practices must recognise and attend to the broader
      social contexts in which they are embedded.

PMID- 19173099
TI  - An exploratory study of aging and perceptual-motor expertise in handball
      goalkeepers.
AB  - Few studies have examined the effect of age on skilled perception. The purpose of
      this study was to determine whether the perceptual-motor abilities of highly
      skilled performers in dynamic, time-constrained sports exhibited the same pattern
      of age-related decline seen in other areas. The sample for this study involved
      five age-specific groups of handball goalkeepers. Each participant completed an
      eye-tracking task, a temporal occlusion task, and an eight-choice reaction time
      task. Results revealed age-related declines in motor performance but not
      perceptual performance. Skilled perception appears resistant to normal age
      related declines over time through the use of compensatory mechanisms.

PMID- 19173100
TI  - Global self-esteem across the life span: a cross-sectional comparison between
      representative and self-selected internet samples.
AB  - The cross-sectional trajectory of global self-esteem across the life span was
      examined administering the Rosenberg and Single-Item Self-Esteem scales to
      Estonians (N = 29,463) who were either randomly selected from the National Census
      to represent the population or self-recruited through the Internet. The results
      (a) challenge the recent conclusion of a universal age trajectory of self-esteem,
      (b) demonstrate that self-recruited Internet data collection method is biased
      compared to random sampling, and (c) present that different self-esteem items
      have dissimilar trajectories. A variance component analysis confirmed that age
      differences in self-esteem are relatively small compared to interindividual
      differences and measurement error.

PMID- 19173101
TI  - Social engagement and cognitive function in old age.
AB  - We examined the association of diverse measures of social engagement with level
      of function in multiple cognitive domains in 838 persons without dementia who had
      a mean age of 80.2 (SD = 7.5). Social network size, frequency of social activity,
      and level of perceived social support were assessed in linear regression models
      adjusted for age, sex, education, and other covariates. Social activity and
      social support were related to better cognitive function, whereas social network
      size was not strongly related to global cognition. The results confirm that
      higher level of social engagement in old age is associated with better cognitive
      function but the association varies across domains of social engagement.

PMID- 19173102
TI  - Change in frailty and risk of death in older persons.
AB  - The authors developed and validated a continuous composite measure of frailty and
      examined its rate of change in 832 older persons with annual evaluations for up
      to 8 years. In generalized estimating equation models adjusted for age, sex, and
      education, there was a significant increase in frailty during follow-up. In a
      proportional hazards model controlling for age, sex, education, and baseline
      frailty, each 1-unit increase in annual change in frailty was associated with an
      almost 5 times the risk of mortality. Using a continuous measure, the authors
      document that frailty is progressive in some older persons and that its rate of
      progression is associated with mortality.

PMID- 19173103
TI  - Inhibition and retrieval of facts in young and older adults.
AB  - Inhibition is considered to have an important role in memory retrieval. However,
      many experimental results suggest that its efficiency declines with aging. In
      this study, the authors tested this hypothesis by using the retrieval-practice
      task. The retrieval-induced forgetting (RIF) observed with this paradigm is
      normally explained in terms of inhibition. Young (mean age 21.5 years) and older
      (mean age 71.6 years) adults studied sets of four shared-subject sentences. A
      retrieval-practice phase required participants to repeatedly recall a subset of
      the studied sentences. In the final test, participants were provided item
      specific cues and told to recall all the studied sentences. RIF was similar for
      both age groups, suggesting comparable inhibitory efficiency in young and older
      adults.

PMID- 19173104
TI  - Age-related decline in mentalizing skills across adult life span.
AB  - In the literature, there are few and conflicting reports regarding age-related
      changes in adult mentalizing abilities: whereas Happe et al. (1998, Developmental
      Psychology, 34, 358-362) showed better performances of elderly compared with
      young subjects in an advanced theory of mind (ToM) task, Mayor et al. (2002,
      British Journal of Psychology, 93, 465-485) and Sullivan and Ruffmann (2004,
      British Journal of Psychology, 95(Pt 1), 1-18) found an age-related decline.
      Former studies addressing the issue compared young to elderly subjects and did
      not investigate earlier changes in middle-aged adults. To shed light on changes
      in ToM skills along adulthood, the authors used the revised version of the
      "Reading the Mind in the Eyes Test" (Baron-Cohen et al., 2001, Journal of Child
      Psychology and Psychiatry, 42, 241-251) to compare four groups of people of
      different ages covering the whole span of adult life. The authors found aged
      related decline in ToM skills as early as the fifth decade of life. Awareness of
      the age-related changes in adult mentalizing is important to differentiate normal
      aging effects from ToM impairments due to neuropsychiatric diseases.

PMID- 19173105
TI  - Optimal time-of-day and consolidation of learning in younger and older adults.
AB  - The current study investigated the relationship between intraindividual
      variability and associative learning in younger and older adults. The authors
      hypothesized that higher levels of intraindividual variability would be
      associated with a reduction in the benefits of practice during learning, and that
      nonoptimal testing times would magnify these effects. Results indicated that
      older adults showed an increase in reaction time (RT) standard deviation (SD)
      relative to mean RT in the evening. Although time-of-day did not have a
      significant effect on rate of learning or total learning, intraindividual
      variability did predict learning rate of younger adults at nonoptimal testing
      times. Results are discussed in light of theoretical models of aging and
      learning.

PMID- 19173106
TI  - Components of speech prosody and their use in detection of syntactic structure by
      older adults.
AB  - Young and older adults heard sentences in which one character was describing
      another character ("The doctor said the nurse is thirsty"), where the character
      being described could be determined only by the prosodic pattern in which the
      sentence was heard. Using computer editing, the authors generated sentences that
      were heard with either one (Experiment 1) or two (Experiment 2) of three
      ordinarily co-occurring prosodic features reduced (pitch variation, amplitude
      variation, timing variation). For both age groups, timing variation was the most
      valuable of the three prosodic features. These results add to our understanding
      of the effective preservation of spoken language comprehension in normal aging.

PMID- 19173108
TI  - Electrophysiological correlates of word comprehension: event-related potential
      (ERP) and independent component analysis (ICA).
AB  - In this study we asked to what extent auditory evoked potentials can help us to
      understand the complex processes underlying word comprehension. Monosyllabic and
      bisyllabic words were presented to 34 young adults in the context of a semantic
      category judgment. The basic paradigm assessed the typicality effect, the
      tendency for classification of members of a category to be made more accurately
      and more rapidly for strong exemplars than for weak exemplars. Event-related
      potentials (ERPs) were recorded from 30 active scalp electrodes. The ERP waveform
      in response to the semantic categorization of a word was characterized by unique
      activity in four temporal intervals; (1) a negative peak at a latency of about
      100 ms, (2) a positive peak at a latency of about 200 ms, (3) a broad negativity
      extending over the latency range from 200 to 600 ms, and (4) a broad positivity
      extending from 600 to 1400 ms. Independent component analysis (ICA) of the
      individual EEG epochs yielded four maximally independent components, interpreted
      as (1) exogenous detection of a change in the acoustic environment, followed by
      allocation of cognitive resources, especially sustained attention, to the
      analysis of subsequent acoustic events, (2) phonological processing, (3) semantic
      processing, and (4) decision processing. The morphologies of the four ICA
      waveforms were consistent with a parallel processing, interactive model of word
      recognition, and subsequent semantic categorization.

PMID- 19173109
TI  - Hearing loss features in GJB2 biallelic mutations and GJB2/GJB6 digenic
      inheritance in a large Italian cohort.
AB  - The aim of this study was to describe the clinical features of hearing loss due
      to mutations on connexin 26/30 coding genes (GJB2/GJB6). Mutations in the GJB2
      gene are found to account for approximately 50% of cases of autosomal recessive
      non-syndromic deafness. Several European studies have estimated that the GJB2
      healthy carrier condition involves about 2-4% of the population, with the 35delG
      mutations being the most common. A 342-kb deletion truncating the GJB6 gene
      (encoding connexin-30) has been associated with autosomal recessive non-syndromic
      deafness, mostly as digenic inheritance of the Cx30 deletion/Cx26 mutation. The
      following retrospective study describes audiological features and genotypes of a
      large cohort of 376 Italian hearing-impaired patients who underwent genetic
      screening for the GJB2/GJB6 genes and received follow-up care at our centre
      between January 2002 and October 2006. Sixteen different genotypes causing
      deafness in more than 27% of patients with either biallelic mutations or digenic
      inheritance GJB2/GJB6 were identified. The most frequent mutations were 35delG,
      M34T, L90P, and R184P.

PMID- 19173110
TI  - Long-term administration of salicylate enhances prestin expression in rat
      cochlea.
AB  - Salicylate, a common drug frequently used long term in the clinic, is well known
      for causing reversible hearing loss and tinnitus. Our previous study, however,
      demonstrated that chronic administration of salicylate progressively raised the
      amplitude of distortion product of otoacoustic emissions (DPOAEs), which are
      mainly caused by (outer hair cell) OHC electromotility. How salicylate affects
      OHC electromotility to cause this paradoxical increase remains unclear. One
      possibility is that it could affect prestin, which is a motor protein that
      contributes to the mechano-electrical properties of OHCs. In this experiment, we
      assessed the effect of acute and chronic salicylate treatment on prestin
      expression. Interestingly, after long-term salicylate injection (200 mg/kg, twice
      daily for 14 days), prestin gene and protein levels were up-regulated about
      twofold. These levels returned to baseline 14 days after treatment stopped. Acute
      injection of salicylate (single injection, 400 mg/kg) did not affect prestin
      levels. These data reveal that chronic salicylate administration markedly, but
      reversibly, increased prestin levels which may contribute to the enhanced DPOAE
      amplitudes we observed previously with similar salicylate treatment, which may be
      responsible for salicylate-induced tinnitus generation.

PMID- 19173111
TI  - Measuring outcome from vestibular rehabilitation, part II: refinement and
      validation of a new self-report measure.
AB  - A prototype self-report measure of vestibular rehabilitation outcome is described
      in a previous paper. The objectives of the present work were to identify the most
      useful items and assess their psychometric properties. Stage 1: One hundred fifty
      five participants completed a prototype 36-item Vestibular Rehabilitation Benefit
      Questionnaire (VRBQ). Statistical analysis demonstrated its subscale structure
      and identified redundant items. Stage 2: One hundred twenty-four participants
      completed a refined 22-item VRBQ and three established questionnaires (Dizziness
      Handicap Inventory, DHI; Vertigo Symptom Scale short form, VSS-sf; Medical
      Outcomes Study short form 36, SF-36) in a longitudinal study. Statistical
      analysis revealed four internally consistent subscales of the VRBQ: Dizziness,
      Anxiety, Motion-Provoked Dizziness, and Quality of Life. Correlations with the
      DHI, VSS-sf, and SF-36 support the validity of the VRBQ, and effect size
      estimates suggest that the VRBQ is more responsive than comparable
      questionnaires. Twenty participants completed the VRBQ twice in a 24-hour period,
      indicating excellent test-retest reliability. The VRBQ appears to be a concise
      and psychometrically robust questionnaire that addresses the main aspects of
      dizziness impact.

PMID- 19173112
TI  - The perception of prosody and speaker gender in normal-hearing listeners and
      cochlear implant recipients.
AB  - The purpose of this study was to examine the effects of altering the fundamental
      frequency (F0) on perception of prosody and speaker gender in both normal-hearing
      listeners and cochlear implant (CI) recipients. Tests with natural speech and
      defined modifications of the F0 were performed, and the resulting changes in
      perception were measured. Compared to the normal-hearing listeners, most of the
      CI users exhibited worse outcomes, especially for sentence stress. In contrast,
      the speaker gender tests yielded similar results for both groups when
      artificially modifying the F0 contour. The results seemed to be strongly related
      to the duration of alterations in F0. Although the perception of prosodic cues
      was limited in most of the CI recipients, they showed qualitatively similar
      results to normal-hearing listeners in that the boundary between questions and
      statements and between female and male voices was comparable. A large inter
      individual difference in performance was observed among the CI recipients, which
      could not be attributed to different processor or implant types or to other
      factors such as implant experience.

PMID- 19173117
TI  - Automatic speech recognition (ASR) and its use as a tool for assessment or
      therapy of voice, speech, and language disorders.
AB  - In general opinion computerized automatic speech recognition (ASR) seems to be
      regarded as a method only to accomplish transcriptions from spoken language to
      written text and as such quite insecure and rather cumbersome. However, due to
      great advances in computer technology and informatics methodology ASR has
      nowadays become quite dependable and easier to handle, and the number of
      applications has increased considerably. After some introductory background
      information on ASR a number of applications of great interest for professionals
      in voice, speech, and language therapy are pointed out. In the foreseeable
      future, the keyboard and mouse will by means of ASR technology be replaced in
      many functions by a microphone as the human-computer interface, and the computer
      will talk back via its loud-speaker. It seems important that professionals
      engaged in the care of oral communication disorders take part in this development
      so their clients may get the optimal benefit from this new technology.

PMID- 19173118
TI  - Antimicrobial effect and resistant regulation of Glycyrrhiza uralensis on
      methicillin-resistant Staphylococcus aureus.
AB  - In the present study, we investigated antimicrobial activity of Glycyrrhiza
      uralensis against various strains of methicillin-resistant Staphylococcus aureus
      (MRSA) (KCCM 11812, 40510, 40512). Glycyrrhiza uralensis was extracted by 80%
      MeOH and fractionated by organic solutions. The extract and fractions showed
      antimicrobial activity against standard S. aureus as well as MRSA. In the minimum
      inhibitory concentration test, G. uralensis showed 0.25 mg mL(-1) in hexane
      fraction and 0.10-0.12 mg mL(-1) in chloroform fraction. Especially, chloroform
      fraction showed 2.5 times higher antimicrobial activity than penicillin.
      Furthermore, chloroform fraction correlated with MRSA gene expression (MecA,
      MecI, MecRI, FemA). These results suggest that G. uralensis may have potent
      antimicrobial activity and thus, this medicinal herb can be a suitable
      phytotherapeutic agent for treating MRSA infections.

PMID- 19173119
TI  - The relaxation mechanisms of tetrandrine on the rabbit corpus cavernosum tissue
      in vitro.
AB  - The relaxation mechanisms of tetrandrine (Tet) on the rabbit corpus cavernosum
      tissue in vitro were investigated. Strips of rabbit corpus cavernosum were
      mounted in organ chambers. The effects of Tet were examined on isolated muscle
      strips pre-contracted with phenylephrine (PE) alone, in the presence of N(W)
      nitro-L-arginine (LNNA, a nitric oxide synthase inhibitor), 1-H
      [1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one(ODQ, a guanylyl cyclase inhibitor),
      indomethacin (cyclooxygenase inhibitor), tetraethylammonium (TEA, Ca(2+)
      activated K(+) channel blocker), 4-aminopiridine (4-AP, voltage dependent K(+)
      channel blocker) and glibenclamide (ATP sensitive K(+)channel blocker). The
      effects of Tet on KCl-induced contraction of isolated muscle strips were also
      investigated. The procedure of calcium absence-calcium addition was designed to
      observe the effect of Tet on the two components of the contractile responses to
      PE based on the source of Ca(2+) (extracellular vs. intracellular). Corpus
      cavernosum strips showed relaxation in response to Tet (10(-8) approximately 10(
      3) mol L(-1)) in a concentration-dependent manner with an IC(50) of 3.73 x 10(-5)
      mol L(-1). However, they were not affected by LNNA, ODQ, indomethacin and K(+)
      channel blockers. Tet (10 micromol L(-1), 30 micromol L(-1)) concentration
      dependently reduced the maximal contraction response of isolated strips induced
      by KCl to (73.0 +/- 3.8) and (41.5 +/- 3.4)%, respectively (p < 0.01). In the
      procedure of calcium absence-calcium addition, Tet 100 micromol L(-1) inhibited
      both intracellular calcium-dependent and extracellular calcium-dependent
      contraction induced by PE (20 micromol L(-1)) (p < 0.05). The inhibition ratios
      were (23.8 +/- 7.1) and (40.7 +/- 11.2)%, respectively. The results of the
      present study suggest that Tet possesses a relaxant effect on rabbit corpus
      cavernosum tissues, which is attributable to the inhibition of extracellular
      Ca(2+) influx and the inhibition of release of intracellular-stored Ca(2+), but
      not mediated by the release of nitric oxide, prostaglandins or by the activation
      of potassium channels.

PMID- 19173120
TI  - Two new flavanone glycosides from Veratrum nigrum L.
AB  - Two new flavanone glycosides have been isolated from the water soluble part of
      Veratrum nigrum L., belonging to the family Lilica. The structures of 3',4'
      dimethoxyl-quercitrin and 4'-methoxyl-glucotricin have been established with the
      aid of extensive NMR spectroscopic studies.

PMID- 19173121
TI  - Influence of growth regulators and sucrose concentrations on growth and
      rosmarinic acid production in calli and suspension cultures of Coleus blumei.
AB  - Rosmarinic acid, which is reported to have adstringent, antibacterial, antiviral
      and antioxidant activities, is one of the most prominent secondary compounds in
      Coleus blumei (Lamiaceae). Rosmarinic acid (RA) production in different hybrids
      of C. blumei was estimated by HPLC. Conditions for HPLC were as follows: column,
      150 x 4.6 mm; solvent system, methanol -0.1% phosphate (45 : 55); flow rate, 0.9
      mL/min; detection: 325 nm. Two out of four hybrids of C. blumei (hy1; hy2)
      contain better rosmarinic acid production (0.9 and 1.0% dry weight, respectively)
      and the leaves have the highest rosmarinic acid production, followed by stems and
      roots. The hydroxyphenylpyruvate reductase (HPPR) gene expression levels were
      analysed by semi-quantitative RT-PCR. Hy3 shows highest level of HPPR gene
      expression out of four hybrids on genotype-specific patterns, and stems represent
      the highest level of HPPR gene expression among leaves, roots and stems. This was
      probably a result of the fact that the RA biosynthetic pathway was regulated by
      interactions of several enzymes necessary for biosynthesis. The explants from the
      hy1 leaves were used in subsequent studies on the effect of different growth
      regulators (2.0 mg L(-1) 6-benzyl-aminopurine (6-BA), different 2,4
      dichlorophenxyaretic acid (2,4-D) and alpha-naphthaleneacetic (NAA)
      concentrations) and sucrose contents (1, 2, 3, 4, 5 or 6%) on culture growth and
      rosmarinic acid accumulation. On the effect of different growth regulators, the
      best result is obtained when the B5-medium supplemented is with 2.0 mg L(-1) 6
      BA, 0.5 mg L(-1) NAA, 0.8 mg L(-1) 2,4-D and 2% sugar, and solidified with 0.8%
      agar. In this case, both growth index and rosmarinic acid accumulation reach a
      maximum, which is 49.7 and 25.3% (dry weight), respectively. The optimal medium
      for suspension culture growth contains 2.0 mg L(-1) 6-BA, 0.5 mg L(-1) NAA, 0.8
      mg L(-1) 2,4-D, 600 mg L(-1) inositel and 2% sugar, and the rosmarinic acid
      production is 1.7% (dry weight). The rosmarinic acid accumulation is enhanced by
      the sucrose concentrations. When the sucrose content is 6%, the calli and cell
      culture accumulate 33.7% (dry weight) and 10.1% (dry weight) rosmarinic acid,
      respectively. Higher sucrose content (>or=5%) has a negative influence on culture
      growth. B5-medium supplemented with 2.0 mg L(-1) 6-BA, 0.5 mg L(-1) NAA, 0.8 mg
      L(-1) 2,4-D, 4% sugar and 0.8% agar is best for both culture growth and
      rosmarinic acid accumulation. On the basis of the above results, we can establish
      a two-phase culture system by calli of C. blumei for the biosynthesis of RA. In
      the growth phase, the calli grow well, but with lower RA production in a modified
      B5-1A medium with 2% sucrose. The calli are then subcultured to B5-1A medium with
      6% sucrose where the calli start to accumulate RA, but grow slowly.

PMID- 19173122
TI  - New principles from seeds of Nigella sativa.
AB  - A new triterpene saponin and known steroidal glucoside were isolated from the
      alcohol extract, and a new cycloartenol from n-hexane extract of seeds of Nigella
      sativa L. and were identified as 3-O-[beta-D-xylopyranosyl-(1-->2)-alpha-L
      rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranosyl]-11-methoxy-16,23-dihydroxy-28
      methylolean-12-enoate (1), stigma-5,22-dien-3-beta-D-glucopyranoside (2) and
      cycloart-23-methyl-7,20, 22-triene-3beta,25-diol (3), respectively. They were
      characterised on the basis of spectral analysis and comparison with literature
      data. The hexane and alcohol extract of the seeds showed antimicrobial activity.
      The antioxidant activity of hexane extract is also described.

PMID- 19173123
TI  - Chemical composition, antimicrobial and antioxidant activities of Centaurea
      ensiformis Hub.-Mor. (Asteraceae), a species endemic to Mugla (Turkey).
AB  - The n-hexane, chloroform, ethyl acetate and ethyl alcohol extracts of the aerial
      parts of Centaurea ensiformis, endemic to Turkey, have been assessed for
      antimicrobial and antioxidant activities. The chemical composition of the hexane
      extract of this plant was determined. The antimicrobial activities on
      microorganisms, including multiple antibiotic resistant bacteria, were evaluated
      using the disc diffusion method. The antioxidant activities were determined by
      using four complementary in vitro assays: inhibition of 2,2-diphenyl-1
      picrylhydrazyl radical, total antioxidant activity, and the total amount of
      phenolic and flavonoid compounds. The structure of the active extract was
      elucidated by: thin layer chromatography, column chromatography, gas
      chromatography or gas chromatography-mass spectrometry. The various extracts of
      C. ensiformis inhibited the growth of tested bacteria. All the C. ensiformis
      extracts had no effect on the yeasts. The total antioxidant activity increased
      with the increasing amount of the extracts (20, 40, 80 and 160 microg), which
      contained linoleic acid emulsion. The major compounds of the hexane extract of
      the plant were caryophyllene oxide (28.72%), spathulenol (17.81%), eudesmol
      (13.03%) and beta-bourbonene (8.51%).

PMID- 19173124
TI  - Phenolic contents, antioxidant and antibacterial activities of Hymenocardia
      acida.
AB  - This study investigates the antioxidant and antibacterial activities of aqueous
      and methanolic extracts from Hymenocardia acida Tul. (Hymenocardiaceae). The
      inhibition values of the extracts and quercetin were found to be very close, with
      no significant differences at a concentration of 0.05 mg mL(-1) in their ability
      to inhibit 1,1-diphenyl-2-picrylhydrazyl (DPPH). Total proanthocyanidins for both
      water and methanol extracts were 20.2 +/- 0.01 and 30.6 +/- 0.51 mg g(-1)
      (catechin equivalent) while the total phenol contents were 20.0 +/- 0.52 and 35.6
      +/- 1.42 mg mL(-1) (tannic acid equivalent), respectively. Positive correlations
      R(2) = 0.85, R(2) = 0.94, R(2) = 0.97 for DPPH, reducing power and 2'-azino-bis(3
      ethylbenzo thiazoline)6-sulphonic acid (ABTS). Linear regression analysis also
      produced a high correlation coefficient with total proanthocyanidins (DPPH, R(2)
      = 0.69; ABTS, R(2) = 0.94). H. acida extracts showed low antibacterial activity
      (minimum inhibitory concentration (MIC) value >or=5.0 mg mL(-1)) against gram
      negative bacteria but significantly (MIC value <or=2.5 mg mL(-1)) inhibited the
      growth of the gram positive strains tested. Qualitative TLC of the extract was
      positive for flavonoids, phenols, steroids and triterpenoids. The results of this
      study support the use of H. acida in traditional Nigerian medicine and show that
      the alcoholic extract of the leaves can be used as an easily accessible source of
      natural antioxidant and can be of assistance in some dermatological problems.

PMID- 19173125
TI  - An antiplasmodial new (bis)indole alkaloid from the hard coral Tubastraea sp.
AB  - Tubastarea sp., a stony coral (Dendrophylliidae) from the Great Hanish in the
      Archipelago of the Hanish Islands, Yemen, contains, in addition to the known
      aplysinopsin (1) and 6-bromo-3'-deimino-3'-oxoaplysinopsin (2), the new
      bis(indole) alkaloid (3). The structures of compounds (1-3) were elucidated by
      interpretation of spectral data. Compound 3 inhibits the growth of Plasmodium
      falciparum (chloroquine-resistant strain) with an IC(50) 1.2 microg mL(-1).

PMID- 19173126
TI  - Unusual amount of (-)-mesquitol from the heartwood of Prosopis juliflora.
AB  - A large amount of flavonoid has been extracted and isolated from the heartwood of
      Prosopis juliflora, an exogenous wood species of Kenya. Structural and
      physicochemical elucidation based on FTIR, (1)H and (13)C NMR, GC-MS and HPLC
      analysis clearly demonstrated the presence of (-)-mesquitol as the sole compound
      without any noticeable impurities. The product was able to slow down oxidation of
      methyl linoleate induced by AIBN. The important amount and high purity of (-)
      mesquitol present in the acetonic extract of P. juliflora could therefore be of
      valuable interest as a potential source of antioxidants from a renewable origin.

PMID- 19173128
TI  - A statement of retraction.

PMID- 19173127
TI  - Chemical and biological comparisons on supercritical extracts of Tanacetum
      cinerariifolium (Trevir) Sch. Bip. with three related species of chrysanthemums
      of Sardinia (Italy).
AB  - In this manuscript, the authors compare the chemical composition and the
      biological effects of extracts of some Sardinian plant species: Glebionis
      coronaria (L.) Spach [=Chrysanthemum coronarium L.], locally known as
      'caragantzu', Glebionis segetum (L.) Fourr. [=Chrysanthemum segetum L.], known as
      'caragantzu masedu', and Sardinian endemic species Plagius flosculosus (L.) Alavi
      and Heywood [=Chrysanthemum flosculosus L.], known as 'caragantzu burdu'. In
      addition, the authors compare the pyrethrins contained in these species with an
      extract of Tanacetum cinerariifolium (Trevir.) Sch. Bip. [=Chrysanthemum
      cinerariifolium (Trevir.) Vis.], a commercial species rich in pyrethrins. The
      volatile fractions from chrysanthemum flowers were obtained by supercritical
      fluid extraction (SFE) with CO(2) at 90 bar and 50 degrees C and by
      hydrodistillation. Pyrethrins were extracted, together with other high molecular
      mass compounds, by SFE at high pressure, 300 bar and 40 degrees C. The
      composition of the volatile oils is determined by GC-MS analysis and the amount
      of pyrethrins by HPLC analysis. Moreover, the antibacterial and antimycotic
      activities of volatile fractions were investigated in order to compare to their
      traditional uses.

PMID- 19173129
TI  - Antimicrobial activity of tigecycline and comparative agents against clinical
      isolates of staphylococci and enterococci from ICUs and general hospital wards at
      three Swedish university hospitals.
AB  - The activities of tigecycline and comparative agents on staphylococci and
      enterococci isolated from patients at general hospital wards (GHWs) and intensive
      care units (ICUs) at 3 university hospitals in Sweden were investigated.
      Oxacillin disc diffusion and minimal inhibitory concentration with E-test were
      used. The presence of mecA, vanA or vanB genes was determined with PCR.
      Statistically significant higher incidence of clindamycin, fusidic acid,
      rifampicin and multidrug-resistant CoNS was found at ICUs compared to GHWs.
      Resistance rates were low among S. aureus. Tigecycline, linezolid and vancomycin
      were the only agents with high activity against methicillin-resistant S. aureus
      and multidrug-resistant CoNS. Resistance rates were low among E. faecalis, except
      for high-level gentamicin-resistant (HLGR) E. faecalis. E. faecium showed high
      resistance rates to ampicillin, piperacillin/tazobactam and imipenem. The HLGR
      rates among E. faecium were lower than the rates for E. faecalis. Tigecycline and
      linezolid were the only drugs with high activity against all enterococci
      including vancomycin-resistant enterococci. No statistically significant
      differences in susceptibility rates were found between the ward levels for S.
      aureus and enterococcal isolates and no statistically significant differences
      were found between the hospitals.

PMID- 19173130
TI  - Psychometric properties of the Worker Role Self-assessment instrument used to
      evaluate unemployed people in Sweden.
AB  - The aim was to determine the psychometric properties of the new Worker Role Self
      assessment (WRS) instrument. The content validity, utility, test-retest
      reliability, sensitivity to change, and predictive validity of the WRS were
      investigated in two subject samples, which were selected at work and pain
      rehabilitation clinics, respectively. One of these groups consisted of 23 clients
      and four occupational therapists, and the other comprised 83 clients. All clients
      in both samples were unemployed. The results showed that both the clients and the
      occupational therapists perceived the content validity and the utility of the WRS
      as good. The test-retest reliability showed mostly good to moderate agreement,
      and the internal consistency was satisfactory. One of the items showed predictive
      validity for work capacity, and the same item was sensitive to change. However, a
      ceiling effect reduced the utility and the sensitivity to change. Our findings
      indicate that the WRS is promising as a tool that clinicians can use to evaluate
      the capacity for return to work and for planning interventions, although some
      revisions are needed to counteract the ceiling effect.

PMID- 19173131
TI  - The challenged values of family medicine.

PMID- 19173132
TI  - [Posterior capsular opacification: one factor to be considered for the study of
      the optic nerve].

PMID- 19173133
TI  - [Topical interferon alfa-2b or surgical excision for primary treatment of
      conjunctiva-cornea intraepithelial neoplasia].

PMID- 19173134
TI  - [Conjunctival tumors].
AB  - Conjunctival tumors are one of the most frequent of the eye and adnexa. They
      comprise a large variety of conditions, from benign lesions such as nevus or
      papilloma, to malignant lesions such as epidermoid carcinoma or melanoma which
      may threaten visual function and the life of the patient. They can arise from any
      cellular component, but the most frequent are of epithelial and melanocytic
      origin. Early diagnosis is essential for preventing ocular and systemic spread
      and to preserve visual function. In this paper we review the clinical
      characteristics of the most frequent conjunctival tumors, and we discuss tumor
      management.

PMID- 19173135
TI  - [Effect of double anaesthetic Colicursi (tetracaine 0.1% and oxybuprocaine 0.4%)
      on central and paracentral corneal thickness].
AB  - OBJECTIVE: To study the effect of 1 drop of combined topical anaesthesia
      (tetracaine 0.1% and oxybuprocaine 0.4%) on central corneal thickness (CCT)
      values and at 2.5 mm from the corneal centre in nasal, temporal, superior and
      inferior hemi meridians, monitored by Orbscan over a period of 16 minutes.
      MATERIALS AND METHODS: The corneal thickness of 12 right eyes of 12 young healthy
      men was determined using the Orbscan Topography System. Values were determined at
      the centre and paracentral regions 2.5 mm from the centre every 2 minutes for 16
      minutes before and after the administration of 1 drop of double anaesthetic
      Colircusi which contains tetracaine 0.1% and oxybuprocaine 0.4%. RESULTS: There
      was no obvious trend of central and paracentral corneal thickness value change
      before and after administration of Colircusi (paired ANOVA, p>0.05). Although
      corneal thickness variation was not statistically significant, higher differences
      were observed at the 6 minute time-point for CCT and at 8 minutes for nasal
      paracentral corneal thickness. CONCLUSIONS: One drop of double anaesthetic
      Colircusi with tetracaine 0.1% and oxibuprocaine 0.4% does not produce any
      significant change in central corneal thickness or in paracentral regions 2.5 mm
      from the centre (nasal, temporal, superior and inferior hemi meridians).

PMID- 19173136
TI  - [Pars plana vitrectomy, phacoemulsification and intraocular lens implantation for
      the management of cataract and proliferative diabetic retinopathy: comparison of
      a combined versus two-step surgical approach].
AB  - PURPOSE: To report the intra-and postoperative complications and visual acuity
      outcomes in pars plana vitrectomy (PPV), phacoemulsification and intraocular lens
      (IOL) implantation in patients with cataract and proliferative diabetic
      retinopathy (PDR). A comparison of the combined versus two-step surgical approach
      is given. METHOD: Retrospective uncontrolled interventional clinical trial. Forty
      eight eyes of 48 consecutive patients with PDR were included. Twenty-eight
      (58.3%) eyes with combined surgery and 20 (41.7%) eyes with sequential surgery
      were analyzed. RESULTS: Postoperative follow-up time was between 6 and 63 months
      (mean: 18 months). 1) Combined surgery: Preoperative best-corrected visual acuity
      (BCVA) ranged from 20/200 to hand motions, and postoperative BCVA ranged from
      20/30 to hand motions. BCVA improved in 17 eyes (60.7%), while in 7 (25%) eyes
      there was no change (> or =2 ETDRS lines) in VA, and in 4 (14.3%) eyes BCVA
      decreased. Postoperative complications included vitreous hemorrhage (VH) in 10
      (35.7%) eyes, and fibrinous exudation in 9 (32.1%) eyes. 2) Two-step surgery:
      Preoperative BCVA ranged from 10/200 to light perception, and from 20/40 to light
      perception in the postoperative period. Best-corrected visual acuity improved in
      15 (75%) eyes, remained the same in 4 (20%) eyes, and decreased in 1 (5%) eye.
      Postoperative complications included fibrinous exudation in 6 (30%) eyes, and VH
      in 3 (15%) eyes. CONCLUSION: Combined PPV, phacoemulsification and IOL
      implantation as well as the two-step procedure are safe and effective for the
      management of cataract in PDR. Sequential surgery could be advantageous to BCVA
      outcomes by minimizing postoperative VH, which is significantly more frequent
      after combined surgery.

PMID- 19173137
TI  - [Surgical removal of peripapillary choroidal neovascularization in young
      patients].
AB  - PURPOSE: To analyze anatomical and visual outcomes after subretinal surgery for
      peripapillary choroidal neovascularization (CNV) not associated with age-related
      macular degeneration (AMD). METHODS: Five eyes from five patients with
      peripapillary CNV who had been treated by subretinal surgery were retrospectively
      analyzed. RESULTS: The patients averaged 32 years of age (range, 11 to 49, SD
      14.5 years) and mean follow-up was 31.4 months (range, 8 to 48, SD 20.8 months).
      Best corrected visual acuity was 0.05 (range, 0.001 to 0.16, SD 0.07) before
      surgery and 0.64 (range, 0.2 to 0.9, SD 0.26) after surgery (p=0.005; Student's t
      test for paired data). Neither intraoperative nor postoperative incidences
      occurred. CONCLUSIONS: Surgical removal may be considered one of the therapeutic
      options to treat peripapillary CNV not related to AMD.

PMID- 19173138
TI  - [Painful incomplete third-nerve palsy caused by an internal carotid-communicating
      posterior artery aneurysm].
AB  - CLINICAL CASE: A 38-year-old woman presented acute-onset, painful incomplete
      third-nerve palsy caused by an internal carotid-posterior communicating artery
      (IC-PC) aneurysm. We describe the differential diagnosis with Tolosa-Hunt
      syndrome and the results after endovascular treatment. DISCUSSION: The presence
      of pupil-sparing third-nerve palsy may not exclude the presence of an IC-PC
      aneurysm and orbital magnetic resonance imaging and/or computed tomography
      imaging must be performed in these cases. The prompt recovery after endovascular
      treatment is consistent with previous reports.

PMID- 19173139
TI  - [Post-traumatic cyclodialysis cleft treated with transscleral diode laser].
AB  - CASE REPORT: A 28-year-old man who received a blunt trauma in his left eye,
      presented with persistent ocular hypotony (intraocular pressure: 4 mmHg) as well
      as loss of visual acuity (0.4), optic disc edema and chorioretinal folds in the
      macula. The foveal thickness, measured by optic coherence tomography, was 326
      microns. Using ultrasound biomicroscopy, a desinsertion of the nasal iris and a
      360 degrees choroidal detachment was observed. The hypotony did not respond to
      conservative treatment and 10 months after the trauma he underwent a transscleral
      cyclopexy with contact diode laser. One year after the laser treatment the visual
      acuity was 1.0, the intraocular pressure 14 mmHg and the foveal thickness 240
      microns. DISCUSSION: Transscleral cyclopexy with diode laser may be an effective
      alternative treatment to resolve post-traumatic cyclodialysis that does not
      respond to medical treatment.

PMID- 19173140
TI  - [Origins of the Miracle Mission].

PMID- 19173141
TI  - [The false dyschromatopsia of the painter Eugene Carriere].

PMID- 19173142
TI  - [To our readers].

PMID- 19173143
TI  - [On the comprehensibility of German hospital quality reports: systematic
      evaluation and need for action].
AB  - OBJECTIVE: This paper focuses on the current resolutions for quality reports of
      German hospitals as released in 2007 as well as on comprehensibility of these
      reports for patients. It is meant to analyse the textual information given by
      these quality reports. Its main objective was to attain a reliable assessment of
      their comprehensibility for patients on the basis of objective measuring methods.
      A further goal was to qualify eventual differences between large and small or
      private and public hospital operators. On the basis of the attained results
      conclusions on the appropriateness of the current legal situation and the
      existing criteria for quality reports were to be drawn. METHOD: The textual
      system part of 200 German hospital reports was analysed as published in the
      Internet (latest download 28th May, 2007). The selection took place by means of a
      controlled sample. The sample structure essentially corresponds to the German
      hospital system structure in terms of bed numbers and its ratio of public and
      private operators. The analysis measured all formal text patterns as well as
      technical terms by means of a computer-aided device. The readability index for
      each text was calculated according to all known readability formulas for the
      German language. RESULTS: German hospital quality reports are readable only for
      those patients who dispose of above-average communicative skills. The analysed
      reports contain more than 10% technical terms while 17% of the chosen words and
      60% of all sentences are too long. 10% of all sentences are too complex and 25%
      comprise more than three technical terms. To understand these texts at least an
      entrance qualification for higher education is required in accordance to
      readability indices. The texts' degree of complexity is comparable to that of
      philosophical papers. Most textual information given by German hospital quality
      reports is proven to be unreadable and incomprehensible for most patients. There
      are no fundamental differences concerning hospital size and operator.
      CONCLUSIONS: The reports' readability and comprehensibility for patients have
      only scarcely been considered in the current legal resolutions, and there is no
      undergoing process of improvement. The analysis has shown that there is in fact
      an urgent need for action. Future reports should therefore ensure that their
      textual content is formulated in a readable and comprehensible recipient-friendly
      manner. To enhance customer-oriented transparency within the German public health
      service patients should be able to fully understand what hospitals want to
      communicate. Therefore the further process of research will focus on the
      development of specific criteria for the production of textual reports. This has
      to be done in co-operation with patients and resident general practitioners.

PMID- 19173144
TI  - [Social differences in the utilisation of prenatal screening, smoking during
      pregnancy and birth weight--empirical analysis of data from the Perinatal Study
      in Bavaria (Germany)].
AB  - INTRODUCTION: Perinatal studies provide an excellent database for public health
      research, to date this potential has rarely been used, however. Taking the
      example of the Perinatal Study in Bavaria, the objective is to demonstrate the
      pros and cons of this database. As it includes only very few variables on socio
      economic status, an additional variable is calculated assessing the socio
      economic status of the community where the mother lives. This is rarely done in
      Germany, and as far as we know the procedure proposed here has not been applied
      before. METHODS: The analyses are based on the data from 2004. They focus on
      three dependent variables: number of prenatal screenings, maternal smoking during
      pregnancy, birth weight of the baby. The following independent variables are
      included as well: age of the mother, nationality of the mother (e.g., German,
      Mediterranean countries), single mother (yes/no), occupational status of the
      mother, community where the mother lives (4- or 5-digit postal code). The socio
      economic status of the community is assessed by the poverty rate, linking two
      other datasets, one for transferring the postal codes to community names, the
      other providing information per community. The multivariate analyses are
      conducted by logistic regressions. RESULTS: Information was available from about
      76 000 births. Concerning the variable 'few prenatal screenings', the analyses
      show an increased risk for mothers from Eastern Europe and from the Mediterranean
      countries, for single mothers and for mothers with low occupational status. The
      risk factor 'maternal smoking during pregnancy' is increased for mothers from the
      Mediterranean countries and for single mothers. It is especially high, however,
      for low status blue collar workers: compared with white collar workers their
      smoking prevalence is 4.67-times (large cities) or even 6.14-times (smaller
      communities) higher. The risk factor 'low birth weight of the baby' is again
      increased for single mothers and for mothers with low occupational status. An
      association with the poverty rate is mainly seen for the variable 'maternal
      smoking during pregnancy', with higher smoking prevalences in the poor
      communities. DISCUSSION: The results demonstrate that the data from the perinatal
      studies are important for public health research. Concerning the risk factors
      analysed here, large social differences can be observed. In order to show time
      trends, it would be important to repeat these analyses on a routine basis. From a
      methodological point of view, it can be stressed that regional differences in
      health and health care have rarely been looked at in Germany, and that the
      procedure proposed here provides a new starting point for closing this research
      gap.

PMID- 19173145
TI  - [Appraisal of resource use in the German health-care system from the perspective
      of the statutory health insurance].
AB  - This paper gives a systematic overview of resource use that is relevant within
      the German health-care system from the perspective of the statutory health
      insurance and how these resource uses should be priced in economic analyses. This
      includes all relevant cost domains from ambulatory and inpatient care as well as
      a detailed description of relevant data resulting from drug usage. For
      prescriptions the legal framework (e.g., reference pricing) is applied to list
      all relevant co-payments or discounts (e.g., for pharmaceutical companies) which
      have to be considered in patented as well as off-patent drugs. The same method is
      applied for ambulatory services [taking the universal remuneration scheme (EBM)
      into account] as well as for inpatient stays (discussing certain characteristics
      of the German DRG system). As a result, for the first time, a pragmatic as well
      as a practical approach is presented to value resource usage within the German
      health care system in future studies from the perspective of the statutory health
      insurance or, in other words, the sickness funds.

PMID- 19173146
TI  - [The Devil is in the details ...].

PMID- 19173147
TI  - [Chances and limits of a standardisation in the appraisal of cost analyses].

PMID- 19173148
TI  - [Developmental model of obesity in early childhood].
AB  - Periods of heightened vulnerability to weight gain have been identified, and
      research supports the notion that obesity has its origins in early life. Maternal
      overweight, maternal smoking during pregnancy, high or low birth weight, rapid
      growth in early infancy, and early adiposity rebound all have been implicated in
      the development of obesity. This paper focuses on susceptibility to increased
      overweight and adiposity during the prenatal period, infancy and mid-childhood,
      and on how factors operating in each of these periods by their timing and
      duration, and also whether other co-factors are present. The persistence of
      obesity from early childhood emphasizes the importance of understanding growth
      trajectories, and a developmental view on early risk factors of adiposity. A
      systematic review of early risk factors may help developing prevention strategies
      to overcome strong influences of obesogenic environments at young age.

PMID- 19173149
TI  - [Integrated intensive treatment of tinnitus: decrease of the tinnitus-related
      distress during a one-year follow-up study].
AB  - AIM OF THE STUDY: The therapy of the chronic tinnitus is aimed at improving the
      way patients cope with their tinnitus and at reducing the tinnitus-related
      distress. The present study investigated the changes of psychometric parameters
      that occurred in patients with chronic tinnitus after 7-days outpatient
      multidisciplinary therapy. The changes were monitored for up to 1 year in order
      to evaluate the long-term efficiency. METHODS: Main emphasis of the intensive
      tinnitus therapy applied was placed on tinnitus habituation and on teaching the
      patients how to apply coping strategies. The main elements of the multimodal
      concept included progressive muscle relaxation according to Jacobson,
      physiotherapy, educative seminars, training of selective attention and, lastly,
      the change of judgment, attitude and behaviour towards tinnitus. Psychometric
      parameters and tinnitus-related distress were assessed prior to and after the
      therapy (at 3, 6 and 12 months) using the tinnitus questionnaire (TQ) according
      to Goebel and Hiller. Furthermore, subjects waiting for therapy (waiting list)
      were recruited to the control group and compared with the therapy group which had
      received therapy 3 months earlier. RESULTS: The therapy group showed a
      significant reduction of the TQ total score after 3 months as compared to the
      control group. Moreover, we observed a long-term, progressive positive outcome
      during the one-year follow-up. The TQ total score was reduced by 10.9 points.
      There was an obvious decrease of the emotional and cognitive distress as well as
      of the intrusiveness of tinnitus, as per evaluation of TQ subscales. CONCLUSIONS:
      The outpatient intensive multidisciplinary tinnitus therapy with long-term
      aftercare has proved to be an effective method in the treatment of patients with
      chronic tinnitus. The outpatient setting enables the instant implementation of
      strategies learned during therapy in the patients' everyday life.

PMID- 19173150
TI  - [Adiposity in children and adolescents--the relevance of prevention and
      rehabilitation].

PMID- 19173152
TI  - [Better network].

PMID- 19173153
TI  - [Pseudomembranous colitis: CT-findings].

PMID- 19173154
TI  - [Stent-assisted intracranial angioplasty: potentials and limitations of pre- and
      postinterventional CT angiography].
AB  - PURPOSE: CT angiography (CTA) is a noninvasive technique for evaluating
      intracranial arterial stenoses and for following up on intracranial stents. We
      analyzed a series of patients to assess the capabilities of CTA with respect to
      preinterventional und postinterventional diagnostic imaging for stent-assisted
      intracranial angioplasty. MATERIALS AND METHODS: We examined 8 patients with 9
      symptomatic intracranial arterial stenoses before and after stent placement with
      CTA. CT angiographies were compared to the periprocedural conventional
      angiography with regard to the quality of the visualization as well as the
      dimensions of the identified stenoses and the implanted stents. RESULTS: The
      extent of the preinterventional intracranial stenoses identified with CTA
      differed between -15% to + 12% from conventional angiography. In any case we were
      able to assess stent position, expansion, and perfusion with postinterventional
      CTA. The mean residual stenosis after stent placement was 33% (13 - 48%) measured
      with conventional angiography and it was accurately estimated with a difference
      of +/- 15% in 5 of 9 stents by CTA. 4 residual stenoses were underestimated or
      overestimated between -20% and + 26%. Further CTA controls of several patients
      showed good visualization of in-stent neointimal hyperplasia. CONCLUSION: CTA is
      useful for stent planning and follow-up of symptomatic intracranial stenoses.
      Intracranial stents and their lumina are adequately visualized by CTA, especially
      in vertebrobasilar vessels. However, residual stenosis and restenosis especially
      in the intracranial internal carotid artery and in the presence of calcified
      plaques may be incorrectly estimated by CTA. In case of doubt patients must
      undergo invasive angiography. In summary the use of CTA is a possibility for the
      primary follow-up of intracranial stents. It cannot generally prevent further
      diagnostics, but it is a potential method for reducing invasive angiography.

PMID- 19173155
TI  - Assessment of left ventricular function parameters with a new three-dimensional
      shape model.
AB  - PURPOSE: To evaluate a 3D model of the left ventricle (LV) which allows
      calculation of LV function parameters on the basis of both short axis (SA) and
      long axis (LA) cine acquisitions. Comparison with the conventional Simpson's rule
      method in a volunteer and patient collective. MATERIALS AND METHODS: Cine imaging
      was performed with a prospectively triggered SSFP sequence: trueFISP: TR 3.6
      msec, TE 1.8 msec, bFFE: TR 3.0 msec, TE 1.4 msec, flip angle 60 degrees ,
      resolution 1.37 x 1.37 mm, slice thickness 8 mm, gap 2 mm in SA orientation from
      apex to basis and in radial LA orientation (spacing 15 degrees) in 11 volunteers
      and 27 patients with mitral valve insufficiency. Five different volume
      computations were compared: Simpson's rule based on all SA slices (M0), 3D shape
      model based on all SA slices (M1a), 3D shape model based on 3 SA slices (M1b), 3D
      shape model based on all SA and LA slices (M2a), and 3D shape model based on 3 SA
      slices and 1 LA slice (M2b). RESULTS: M 0 and M 1a give similar results (r: 0.99,
      b: 0.98). M 2a produces larger volumes than M 0 (b: 0.85) due to the inclusion of
      the LA contours. M 1b effectively reproduces the volumes computed with M 0 (r:
      0.99, b: 1.02). M 2b effectively reproduces the volumes computed with M 2a (r:
      0.99, b: 0.94). M 2b and M 0 give similar results in the patient collective (r:
      0.99, b: 0.97). CONCLUSION: The proposed 3D shape model allows merging of
      information acquired in different orientations and thus the combination of SA and
      LA contours with better coverage of the left ventricle. It provides a suitable
      fit with a reduced number of segmented contours.

PMID- 19173156
TI  - [Application of a clip-based hemostatic device for hemostasis of an artery
      punctured by a port catheter system].

PMID- 19173157
TI  - [Applications of botulinum toxin in ophthalmology].

PMID- 19173158
TI  - [The management of cataract in childhood].
AB  - Congenital and juvenile cataracts are one of the leading causes of childhood
      blindness. About one out of 3000 children has or develops optically significant
      lens opacities that need surgery early in life. Up to the age of two years, the
      eyes remain aphacic and are corrected with contact lenses and bifocal glasses
      following surgery. Beyond the age of two years, IOL implanation is safe and
      sufficiently precise, but requires surgical measures to prevent secondary
      cataract. In congenital cases, surgery should be performed early enough to
      prevent amblyopia, but not too early in order to reduce the likelihood of
      secondary glaucoma. Hence, unilateral cataracts should be operated on in the
      sixth week of life, bilateral ones in the tenth week. Optimal interaction between
      surgeons, orthoptists and parents are prerequisites for good functional outcomes.
      This review covers the most important aspects of the timing of surgery, surgical
      techniques, visual outcomes, complications and postsurgical visual
      rehabilitation.

PMID- 19173159
TI  - [Beyond TGF-beta: wound healing modulation in filtering glaucoma surgery].
AB  - Conjunctival scarring remains the major problem in filtering glaucoma surgery.
      Antimetabolites afford a reduction of scar formation, but considerable side
      effects limit their application. Here, we review the mechanisms and peculiarities
      of wound healing following glaucoma surgery and report on new developments in the
      field of wound healing modulation. The growth factor TGF-beta has a central role
      in wound healing and scarring. Therefore, novel concepts of wound healing
      modulation comprise scavenging of TGF-beta and specific inhibition of disinct
      downstream intracellular signalling pathways. Several compounds have entered
      preclinical evaluation and offer new potential to modulate scarring in future
      combination therapies.

PMID- 19173160
TI  - [Oxidative stress at the retinal pigment epithelium - experimental implications
      for protection].
AB  - Oxidative stress at the retinal pigment epithelium (RPE) is involved in the
      pathophysiology of age-related macula degeneration (ARMD). Observations on a
      clinical or laboratory level have revealed that supplementation of antioxidative
      scavengers failed in many cases. A potential therapeutic target is the cellular
      signal transduction cascade initiated by oxidative stress which results, e. g.,
      in altered expression of pro- and antiagiogenic factors as well as induction of
      apoptosis. This review summarises the current literature on cellular effects of
      free radicals and deduces potential therapeutic approaches to protect the RPE
      from oxidative damage.

PMID- 19173161
TI  - [Macular translocation - a therapeutic approach for neovascular macular
      degeneration in the era of anti-VEGF therapy?].
AB  - Since anti-VEGF treatment has been proven to achieve a significant improvement of
      visual acuity in a cohort of patients with neovascular age-related macular
      degeneration (AMD), macular surgery and particularly the macular translocation
      with 360 degrees retinotomy (FMT: full macular translocation) have lost their
      former popularity. However, the approach of macular surgery still remains a
      promising therapy in selected cases. A prospective randomised study, comparing
      FMT and photodynamic therapy in subfoveal classic choroidal neovascularisation
      (CNV), recently showed the superiority of FMT in terms of visual gain. In spite
      of the postoperative complications and the disturbed binocular vision, the
      reading acuity and the life quality of many patients improved. Therefore, it is
      justified to discuss the chances and advantages of the FMT at least in selected
      cases. After all, case selection was an important determinant also in the phase
      III studies of ranibizumab; many patients seen during the routine consulting
      hours were excluded as a consequence of the study criteria. Most of them were
      suspected to achieve a less favourable outcome of the anti-VEGF regimen. Thus,
      patients who did not meet the inclusion criteria of recent studies or showed no
      response to the anti-VEGF therapy, as well as patients with extensive submacular
      bleeding or ruptures of the pigment epithelium can also be considered as
      candidates of FMT. Generally, in the presence of highly effective anti-VEGF
      drugs, FMT can be discussed for second-line treatment, if the fellow eye has poor
      function and no additional risk factors of the affected eye are known (e. g.,
      hyperopia, large lesion size, etc). Detailed information relating to the
      potential adverse events have to be mentioned. Although the indication is
      restricted, surgeons should have the continuing ability to perform the
      challenging surgical procedure.

PMID- 19173162
TI  - [Retinal damage by perfluorocarbon liquids - a question of specific gravity?
      Intraocular pressure peaks and shearing forces].
AB  - BACKGROUND: Perfluorocarbon liquids (PFCL) cause retinal damage when used as long
      term ocular endotamponades. Whether these changes are related to the mechanical
      or to the chemical properties of PFCL is unclear. The purpose of this study was
      to evaluate pressure spikes or shearing forces during endotamponade with PFCL and
      standardised eye movements. MATERIAL AND METHODS: Part 1: In an eye model the
      resulting pressure forces of 6 PFCL were measured at four different sites during
      standardised eye movements. Part 2: Shearing forces were determined in a
      plexiglass eye model and the resulting tangential forces at the PFCL-retina
      interface were calculated. Part 3: Rabbit eyes were vitrectomised and filled with
      light and heavy fluorocarbons for 6 weeks. Subsequently, the retina were examined
      histologically and by immunohistochemistry. RESULTS: With increasing filling of
      the eye model, the maximum of the pressure peaks moved from the inferior wall of
      the eye model to the lateral eye walls. For perfluorodecalin (PFD) the highest
      pressure peak was 407 Pa with a 75 % filling of the vitreous cavity. The lowest
      pressure peak was 314 Pa with a 50 % filling of hexafluoropropene oxide. Shearing
      forces for standardised accelerations were dependent on viscosity and ranged
      between 0.87 mN/m(2) (perfluorohexyloctane) and 8055 mN/m(2) (hexafluoropropene
      oxide). Part 3: Histological and immunohistochemical analyses did not reveal
      pressure-related damage or any difference between the effects of the different
      tamponades in vivo. CONCLUSION: In comparison with physiological dynamic and
      static pressure peaks, the measured mechanical forces induced by intraocular PFCL
      tamponades are low. Specific gravity and mechanical damage by intraocular PFCL as
      a cause of retinal damage seem unlikely. Animal studies underline these findings.

PMID- 19173163
TI  - [Contact allergy to topical ophthalmological drugs - epidemiological risk
      assessment].
AB  - BACKGROUND: Contact allergies (CA) against active agents of topical
      ophthalmological therapeutics, causing inflammation of the conjunctiva and/or the
      lid, are usually not life-threatening, but occur not infrequently. As yet, the
      assessment of the CA-eliciting risk has been based on clinical data alone, while
      a valid epidemiological risk assessment is lacking. MATERIALS AND METHODS: The
      Information Network of Departments of Dermatology supplied information on
      diagnostic results obtained in 4,102 patients patch-tested for suspected CA to
      ophthalmic drugs between 1995 and 2004. Clinical prevalences were extrapolated to
      incidences at the German population level. These estimates served as numerator
      for a relative incidence (RI), which included the nationwide frequency of
      prescriptions collected by the WIdO, Bonn, in terms of a standardised defined
      daily dose (DDD) as denominator. RESULTS: The estimated annual incidence of CA
      ranges from 155 (atropine sulphate) to 2077 (gentamicin sulphate) and can thus be
      regarded as moderate. If incidence estimates are related to prescription
      frequencies, the highest risk was found for kanamycin and neomycin sulphate (RI >
      8 / 100,000 DDD). In contrast, the RI of pilocarpine-HCl (0.3) was virtually
      negligible. CONCLUSIONS: The substance-specific risk of CA has been evaluated for
      the first time and found to differ between therapeutics (with a similar spectrum
      of application). CA risk should be considered in differential therapeutic
      decision-making.

PMID- 19173164
TI  - [Fluctuation of intraocular pressure in 24-hour telemonitoring compared to
      tonometry during normal office hours].
AB  - BACKGROUND: Elevated intraocular pressure (IOP) is a clinically relevant factor
      in glaucoma progression. As a dynamic parameter the IOP depends on various
      internal and exogenic influencing factors. Therefore, we analysed intraindividual
      IOD variations between ambulant care and 24-h home-monitoring using self
      tonometry. PATIENTS AND METHODS: This study is based on paper-based glaucoma
      cards of 25 patients with primary open angle glaucoma. Additionally, all patients
      participated in a telemedical home-monitoring study with self-measurements of IOP
      and blood pressure stored in an electronic patient record. The glaucoma cards
      contained a total number of 409 IOP values with documentation periods from 0.5 to
      10 years. In the teletonometry project all 25 patients were observed for 6 months
      with 1490 recorded IOP values. Statistical analysis was performed with SPSS
      software. RESULTS: Average IOP values for all 25 glaucoma patients were 16.3 +/-
      2.9 mmHg for both eyes in glaucoma card documentation, whereas the electronic
      patient records showed IOP averages of 18.9 +/- 4.7 mmHg for right eyes and 18.2
      +/- 4.4 mmHg for left eyes. Corresponding to the practice opening hours the
      glaucoma cards contained no IOP records from 12:00 pm to 01:30 pm as well as
      between 06:00 pm and 07:15 am. In these time periods 17 % of all IOP values
      recorded in 24-hour teletonometry were higher than 20 mmHg. However, statistical
      analysis and clinical evaluation of device parameters and measurement
      characteristics revealed sporadic measuring errors. CONCLUSIONS: The additional
      involvement of self-tonometry in telemedical 24-h home-monitoring is a feasible
      method to record and detect intraday IOP fluctuations. Compared to single IOP
      measurements documented in common paper-based glaucoma cards, the 24-h electronic
      patient record showed more frequent circadian IOP variations. As a result, self
      tonometry and home-monitoring can be a useful link to fill the gap between
      singular ambulant IOP measurement and hospitalisation with 24-hour IOP profiles.

PMID- 19173166
TI  - [Vortex keratopathy with unusual central position after LASIK-treatment with
      amiodarone].

PMID- 19173165
TI  - [ITAP - 6-month results of a prospective, randomised phase 3 study for evaluation
      of the combination therapy of PDT and intravitreal triamcinolone in exudative
      AMD].
AB  - BACKGROUND: Combination therapy of photodynamic therapy (PDT) with intravitreal
      triamcinolone (IVTA) for choroidal neovascularisation (CNV) in age-related
      macular degeneration is thought to improve the prognosis. It is therefore widely
      used, although results are mostly based upon non-randomised and retrospective
      studies. Here we present the 6-month results of our prospective, randomised,
      multicentre ITAP trial (Intravitreal Triamcinolone and PDT) for the evaluation of
      the combination therapy as compared to PDT alone. PATIENTS: This prospective,
      randomised, multicentre phase III trial was performed for the evaluation of the
      efficacy and safety of combination therapy (PDT and IVTA) as compared to PDT
      alone. Three randomised therapy groups (A: PDT alone, B: IVTA on the same day 1
      hour after PDT C: IVTA 1 week before PDT) were monitored over 1 year. The
      patients included had wet AMD with predominantly classic CNV, minimal classic CNV
      smaller than 4 papillary diameters or occult CNV with recent disease progression.
      Re-treatment was performed when persistent leakage of the CNV was visible at
      follow-up. Primary outcome criteria were the comparison between combination
      therapy and PDT monotherapy concerning visual acuity, and, second, the comparison
      between the two groups of combination therapy. RESULTS: 92 patients were included
      in the study. Before treatment, mean best corrected ETDRS letter score was 52, 53
      and 51 in groups A, B and C, respectively. At the 6 months follow-up, mean best
      corrected letter score was 40, 47 and 47, respectively, with only group A loosing
      more than 10 letters. This change, however, was not statistically significant
      between the groups. Mean retinal thickness as measured with optical coherence
      tomography decreased in all groups, and reached statistical significance in both
      combination groups. Re-treatment rates did not differ significantly between the
      three groups at 6 months follow-up, nor was there a significant cataract
      progression requiring operation. CONCLUSION: At 6 months there was no significant
      difference between mono- and combination therapy groups concerning visual acuity.

PMID- 19173167
TI  - [Adenoma of the pigmented epithelium of the ciliary body].

PMID- 19173168
TI  - [Intraocular bevacizumab as palliative therapy in melanoma-metastasis-associated
      rubeotic secondary glaucoma].

PMID- 19173169
TI  - [The history of research on depressive disorders at the beginning of modern
      times: John of the Cross].
AB  - OBJECTIVE: The paper examines the importance of the Spanish author John of the
      Cross (1542-1591) for the history of research on depressive disorders. METHODS:
      In view of the allegoric nature of his prose and lyric texts, a critical analysis
      of his work was performed. RESULTS: John of the Cross provides essential
      information not only on diagnostic but also on therapeutic issues. CONCLUSIONS:
      Taking into account the importance he attributes to the spiritual dimension of
      the human nature, an effort is made to show his pioneering role regarding modern
      approaches to the therapy of depressive disorders and to emphasize the need for
      heightened sensitivity towards the spiritual needs and interests of the modern
      patient.

PMID- 19173170
TI  - [Gamma-hydroxybutyrat (GHB)-dependence and -withdrawal in the case of previous
      alcohol dependence].
AB  - OBJECTIVE: gamma-Hydroxybutyrat (GHB) is used medically for narcolepsy and as a
      narcotic. It is also a rare illegal drug. In this case report the development of
      a GHB-dependency against the background of a primary alcohol dependency is
      described. METHODS: Based on established alcohol withdrawal scales (AWSS by
      Wetterling, CIWA) and neuropsychological testing procedures (CGI, GAF, SKID-II,
      PISQ, analog-scale for Craving), the initial situation, the development of
      psychopathological findings, and the course of detoxification were shown.
      RESULTS/CONCLUSION: The combined detoxication of GHB and alcohol was successfully
      finished by a reduction schedule of diazepam. Withdrawal-assessment scales for
      alcohol were helpful, but show limitations for GHB-withdrawal symptoms. The
      patient suffers, according to ICD-10, from a multiple drug dependence (alcohol,
      GHB, abstinence from amphetamines). Symptoms of insomnia, major depression, and
      generalized anxiety disorder can be associated with the use of GHB.

PMID- 19173171
TI  - [Suicides and social neighbourhood characteristics: an ecological analysis in an
      urban German area].
AB  - OBJECTIVE: Ecological analyses on the association between social neighbourhood
      factors and suicide rates have rarely been conducted in German cities. Aim of our
      study was to analyse the association between small area (neighbourhood) social
      characteristics and the suicide frequency within a large German city. METHODS:
      All suicides occurring between 2002 to 2004 in the city of Dortmund were
      registered and death certificates validated. Social indicators for the 62 city
      neighbourhoods were analysed for their influence on suicide frequency using
      correlation and Poisson regression methods. RESULTS: Between 2002 and 2004, 217
      suicides were registered in Dortmund. In women, but not in men, high correlations
      with several social neighbourhood indicators were found. In the regression
      analysis the proportions of married individuals, welfare recipients, and elderly
      citizens (65 years and older) as well as the population density were
      significantly associated with the suicide frequency in the neighbourhoods.
      DISCUSSION: Ecological analyses may suggest details and local starting points for
      suicide prevention programmes.

PMID- 19173172
TI  - [Depression and response: impact of personality and cognition].
AB  - OBJECTIVE: Despite effective pharmacologic and therapeutic strategies some
      patients do not sufficiently benefit from antidepressive treatment. The influence
      of personality and cognition onto response in depressive inpatients shall be
      explored. METHODS: Depressive inpatients were rated concerning depressive
      pathology immediately after admission as well as at discharge. In addition, prior
      to discharge, cognitive performance and personality traits were measured. The
      sample was divided into responders and nonresponders by the reduction of
      depressive symptoms from admission to discharge. For the assumption of response,
      a reduction of minimum 50 % was defined. RESULTS: Preliminary results suggest an
      impact of personality traits onto response in depressive patients, particularly
      extraversion seems to have a salutary effect. Furthermore, significant
      differences between responders and nonresponders were shown concerning alertness.
      CONCLUSIONS: In the treatment of non-response depression, cognitive and
      personality traits should be taken in account by using multimodal strategies.

PMID- 19173174
TI  - [Translation of the Richmond Agitation-Sedation Scale (RASS) for use in German
      Swiss intensive care units].
AB  - In intensive care units, patients are sedated to reduce the stress caused by
      illness and/or treatments such as artificial respiration. Regular assessment of
      the degree of sedation as part of the goal-directed therapy has been recommended
      as a standard of care. The Swiss Society of Intensive Care Medicine requires all
      accredited Swiss intensive care units to periodically document the degree of
      sedation by means of a sedation scale as part of the minimal data set (MDSi). The
      ten-level Richmond Agitation-Sedation Scale (RASS) is one of two proposed scales
      for the assessment of the degree of sedation. Because validated versions of the
      recommended sedation scales exist in English only, the RASS was translated by a
      systematic iterative procedure in six steps. The iterative translation of the
      RASS for use in Swiss intensive care units described in this article is an
      example of interdisciplinary teamwork. Translation of clinical assessment tools
      for clinical use should be carried out as carefully and stringently as the
      development of research tools. Based on the experience gained in the described
      project we recommend the following points to consider when translating clinical
      assessment tools: a) referring to literature not only on the subject of
      translation but also on the process of translation itself, b) involving
      professional translators as language experts, and c) consulting the author(s) of
      the original version.

PMID- 19173173
TI  - [Thrombosis of inferior vena cava complicating tonsillectomy in a case of azygos
      continuation].

PMID- 19173175
TI  - [Impact of a pre-operative mobilisation program using the Viv-Arte training model
      based on kinesthetic mobilisation on mobility, pain, and post-operation length of
      stay of patients receiving an elective medial laparotomy: a prospective,
      randomised, controlled pilot study].
AB  - A medial incision is a common surgical technique to obtain access to the abdomen.
      Thereby, the muscles involved in movement are manipulated, leading to post
      operative restrictions in mobility and pain determined by movement. The aim of
      this pilot study was to assess the impact of a pre-operative training session
      using the Viv-Arte model, which is based on kinesthetic mobilisation principles.
      The parameters to be measured were mobility, pain, and length of hospital stay
      for patients, who were undergoing elective medial laparotomy. In addition, the
      study tested the research design and to identify possible effect sizes. The
      method chosen was a prospective, randomised, controlled, and unblinded design.
      Twenty-seven patients were involved (median=63 years, 19 of the patients were
      male) who were to have a medial incision for cystectomy. The intervention
      involved pre-operative training of post-operative mobility techniques. Mobility
      was tested using the "Mobilitatstest fur Patienten im Akutkrankenhaus (MOTPA)
      (Mobility test for patients in hospital)"; pain intensity was assessed using the
      visual analogue scale. The intervention and control groups were comparable for
      all variables. There were no significant differences in the two groups related to
      the objectives. It is possible that the study groups or the operationalisation
      were not appropriate for testing the effects of the intervention. It seems
      important to continue to develop instruments that are appropriate for measuring
      the effect of mobility-related interventions.

PMID- 19173176
TI  - [Enfuvirtide in HIV patients: a nursing guideline for medication management].
AB  - Fusion inhibitors can be an effective salvage therapy in HIV-patients with
      multiple resistances. However, the management and maintenance of the therapy,
      which requires percutaneous self-administration, can be a difficult task for
      patients. Preparation and administration are time-consuming and may force
      patients to alter their daily routine. Therefore, appropriate counselling and
      training is important. Evidence-based guidelines can help health care
      professionals to provide continuing high quality care. The department of Clinical
      Nursing Science at the University Hospital Basel have developed a nursing
      guideline, which formulates patient-management from decision-making up to the
      support needed in long-time treatment maintenance. The main focus of this article
      lies on the theoretical framework of this guideline and a description of its key
      elements. These are important aspects of managing the treatment of chronic
      illness in general. Therefore, this article addresses all health care providers
      supporting chronically ill patients in their medication management.

PMID- 19173177
TI  - [Nurses' role in the therapeutic team of stroke units].
AB  - Over the last decade, stroke units have been increasingly established in Germany.
      Within these units, nurses have been identified as having a crucial role in the
      coordination of multi-professional team activities. However, currently very
      little data exists to support this fact; therefore, a questionnaire was developed
      to assess various aspects of the nurses' role within the multi-professional team,
      including cooperation with other team members (e.g., communication behaviour and
      acceptance within the multi-professional team), contribution to team and unit
      organisation, and impact on patient recovery. A total of 55 multi-disciplinary
      staff members from three separate stroke units completed the questionnaire.
      Results showed that staff have comparable estimates concerning the nurses' level
      of interdisciplinary cooperation. As well, nurses and other non-medical staff
      rate nurses' contribution to unit organisation comparably high while physicians'
      ratings of nurses' contribution are lower. The professional groups' ratings of
      the nurses' contribution to patient recovery vary. The results indicate that
      German stroke unit nurses contribute significantly to stroke unit care by acting
      as coordinators of the unit organisation for various multi professional team
      members.

PMID- 19173178
TI  - [A portfolio for the development of a Surgical Intensive Care Unit into an
      internationally recognized reference center].
AB  - This article describes the development and content of the portfolio of the
      Surgical Intensive Care Unit. The first step was to evaluate clinical practice
      using a SWOT (strengths, weakness, opportunities and threats) analysis;
      development and trends within surgical intensive care were analyzed with a
      literature search. From these results, three areas were identified as essential
      for the development of practice: (1) best practice/best care, (2) research, and
      (3) development into a reference center. For each area, clearly specified
      objectives, outcomes, measures, responsibilities, and resources were defined and
      an extensive multi-year action plan was established. Best Practice/Best Care
      consisted of the improvement of performance and patient outcomes, the support and
      promotion of personnel, and the implementation of evidence-based nursing
      practice. Combining Best Practice/Best Care with the goals and measures of the
      second area, Research, formed the basis for realizing the vision of the Surgical
      Intensive Care Unit to become "a nationally and internationally recognized
      reference center for surgical intensive care for defined topics and patient
      groups." Concrete strategies for achieving this goal were established in the
      third area.

PMID- 19173180
TI  - Evaluation of [(201)Tl](III) Vancomycin in normal rats.
AB  - BACKGROUND: Tl-201 has potential in the preparation of radiolabelled compounds
      similar to its homologues, like In-111 and radiogallium. In this paper, recently
      prepared [(201)Tl](III) vancomycin complex ([(201)Tl](III)VAN) has been evaluated
      for its biological properties. MATERIAL AND METHODS: [(201)Tl](III)VAN was
      prepared according to the optimized conditions followed by biodistribution
      studies in normal rats for up to 52 h. The Staphylococcus aurous specific binding
      was checked in vitro. The complex was finally injected to normal rats. Tracer
      SPECT images were obtained in normal animals and compared to those of (67)Ga
      citrate. RESULTS: Freshly-prepared [(201)Tl](III)VAN batches (radiochemical yield
      > 99%, radiochemical purity > 98%, specific activity approximately 1.2 Ci/mmol)
      showed a similar biodistribution to that of unlabeled vancomycin. The
      microorganism binding ratios were 3 and 9 for tracer (201)Tl(3+) and tracer
      (201)Tl(III)DTPA, respectively, suggesting the preservation of the tracer
      bioactivity. As a nonspecific cell penetrating tracer, [(201)Tl](III)DTPA was
      used.

PMID- 19173181
TI  - New forms of radionuclide therapy with (90)Y in oncology.
AB  - BACKGROUND: Currently, there is growing interest in the use of the beta emitter
      (90)Y in systemic therapy in oncology. For successful therapy, an appropriate
      ligand is chosen to carry the isotope to the place of its action. As well as
      performing this function, the type of the ligand influences both the course and
      the side effects of the treatment. For RIT of lymphomas, bone marrow becomes the
      critical organ; in NET patients treated with labelled somatostatin analogues,
      increased kidney irradiation can occur. The aim of this study was to evaluate the
      side effects of therapy using 90Y associated with different ligands, depending on
      the charge to critical organs after treatment in two groups of patients: those
      with neuroendocrine tumours and those with non-Hodgkin's lymphomas. MATERIAL AND
      METHODS: 32 patients with histopathologically confirmed NET treated with (90)Y
      DOTATATE (7.4 GBq/m(2) cumulative dose) and 30 NHL patients treated with (90)Y
      ibritumomab tiuxetan (1200 MBq max dose) were enrolled in the study. The kidney
      function and changes of blood indices were assessed during the course of the
      therapy. RESULTS: 59% of NET patients treated with (90)Y-DOTATATE displayed
      transient reduction of blood indices, the largest after cycles III and IV of
      therapy. After 5 months an increase in creatinine level was noticed, but no
      statistically important changes in creatinine level and GFR were observed. In the
      group of patients with NHL, the change of haematological indices after RIT
      concerned mainly PLT, ANC and WBC. The reduction of the average PLT and WBC
      values started in the first weeks after the treatment application, reaching nadir
      in the 6(th) week and 8(th) week, respectively. No life threatening infections
      were observed in either group of patients. CONCLUSIONS: After treatment with the
      use of the (90)Y radionuclide, no significant treatment toxicity, including
      disorders involving the critical organs for both types of therapies, was found in
      the groups of neuroendocrine tumour and non-Hodgkin's lymphoma patients.

PMID- 19173182
TI  - Multiple myeloma: predictive value of Tc-99m MIBI scintigraphy and MRI in its
      diagnosis and therapy.
AB  - BACKGROUND: We assessed the validity of (99m)Tc-MIBI scintigraphy and MRI in the
      diagnosis and prediction of the effect of therapy in patients with multiple
      myeloma (MM) and monoclonal gammopathy of unknown significance (MGUS), in whom
      both examinations were performed within 14 days. MATERIAL AND METHODS: Forty
      seven consecutive patients with MM and 5 with MGUS were enrolled in the study.
      Out of 47 MM patients, 6 were in Durie-Salmon stage I and 41 had active disease
      in stage II or III. Fifteen patients were examined before and within 2 months of
      intensive chemotherapy. Anterior and posterior whole-body scans were obtained 10
      min after IV administration of 740 MBq (20 mCi) (99m)Tc-MIBI. MRI of Th and LS
      spine, T1 w.i. and STIR in the sagittal plane were performed. RESULTS: Bone
      marrow pathological changes in 41 MM patients with active disease were detected
      in 39 (95%) scintigraphic examinations and in 38 (94%) of MRI. Among 41 MM
      patients with active disease, 21 showed diffuse patterns of (99m)Tc-MIBI uptake,
      8 showed focal patterns and 10 showed both focal and diffuse patterns, while 34
      patients exhibited focal lesions in MRI and 4 both focal and diffuse findings.
      Moreover, 5 of 38 patients had epidural mass and 18 had vertebrae compression.
      Out of 15 patients after therapy, 13 reached complete remission and 2 had stable
      disease. Normal (99m)Tc-MIBI scintigraphy was found in 11 (85%) patients with
      complete remission, 2 presented both focal and diffuse patterns of (99m)Tc-MIBI
      uptake. Two patients with stable disease also had focal and diffuse radiotracer
      uptake. MRI findings were normal only in 3 (23%) patients in complete remission.
      Eight patients exhibited focal lesions and 2 showed partial conversion in MRI.
      CONCLUSIONS: (99m)Tc-MIBI scintigraphy and MRI are methods of equal sensitivity
      in detecting active MM and complement each other. The advantage of 99mTc-MIBI
      scintigraphy is the possibility of whole body examination, which allows
      superiority in detection of MM in appendicular skeleton and extramedular lesions,
      and faster response to therapy, while the advantage of MRI is the detection of
      epidural masses and vertebral compressions influencing the therapeutic strategy.

PMID- 19173183
TI  - The role of PET/CT in evaluation of Facet and Disc abnormalities in patients with
      low back pain using (18)F-Fluoride.
AB  - BACKGROUND: Bone scintigraphy including Single Photon Emission Computed
      Tomography (SPECT) is known for its role in the diagnosis of low back pain
      disorders. Positron Emission Tomography (PET) with (18)F (Flouride-18) as a
      tracer can be used to carry out bone scans with improved image quality. With the
      addition of CT, simultaneous PET/CT fused images provide more accurate anatomical
      details. The objectives of this work are to assess the use of (18)F-PET/CT in
      patients with back pain and suspected facetogenic pain, and to find the frequency
      of facet arthropathy versus disc disease abnormalities. MATERIAL AND METHODS: 67
      patients who presented with back pain underwent routine X-ray, CT and/or MRI,
      which failed to identify a clear cause, were referred to (18)F-PET/CT. Among the
      main group, a subset of 25 patients had previous spine surgery consisting of
      laminectomy or discectomy (17 patients) and lumbar fusion (8 patients). The
      PET/CT scan was acquired on a GE VCT 64-Slice combined scanner. Imaging started
      45-60 minutes after administration of 12-15 mCi (444-555 MBq) of (18)F-Fluoride.
      The PET scan was acquired from the skull base through the inguinal region in 3D
      mode at 2 minutes/bed. A lowresolution, non-contrast CT scan was also acquired
      for anatomic localization and attenuation correction. RESULTS: The (18)F-PET/CT
      showed abnormal uptake in the spine in 56 patients, with an overall detection
      ability of 84%. Facet joints as a cause of back pain was much more frequent (25
      with abnormal scans). One-third (36%) of the patients showed multiple positive
      uptake in both facet joints and disc areas (20/56). The patients were further
      divided into two groups. Group A consisted of 42 patients (63%) with back pain
      and no previous operative procedures, and the (18)F-PET/CT showed a high
      sensitivity (88%) in identifying the source of pain in 37/42 patients. Group B
      included 25 patients (37%) with prior lumbar fusion or laminectomy, in which the
      PET/CT showed positive uptake in 76% (19/25 patients). (18)F-PET/CT showed
      positive uptake in all patients (100%) with a history of pain after lumbar
      fusion, while in the laminectomy subgroup only 11 cases (65%) showed positive
      focal uptake. CONCLUSIONS: (18)F-PET/CT has a potential use in evaluating adult
      patients with back pain. It has a promising role in identifying causes of
      persistent back pain following vertebral surgical interventions.

PMID- 19173184
TI  - Conventional and parametric kidney scintigrams - reproducibility of
      semiquantitative image evaluation.
AB  - BACKGROUND: Parametric kidney scintigraphy gives the possibility of regional
      function distribution assessment of these organs; the clinical application of the
      method has thus far been limited. The usefulness of the method for the assessment
      of postinflammatory scars and diabetic nephropathy has been demonstrated.
      Preliminary data also indicate that this type of imaging allows the assessment of
      kidney function after extracorporeal shock wave lithotripsy. The aim of this
      study was the evaluation of the reproducibility of semiquantitative parametric
      kidney image evaluation. MATERIAL AND METHODS: The results of 98 dynamic kidney
      scintigraphic series were evaluated, obtained from examination of 44 patients (20
      males, 24 females) with nephrolithiasis, who had been treated by means of
      lithotripsy. The semiquantitative assessment involved conventional
      renoscintigraphic images obtained from summation of scintigraphic serial records
      in the secretory phase, and parametric clearance images. A 5-level score was
      applied for assessment of both types of images, based upon numbers of detected
      defects of the regional function (0 - no defects; 1, 2, 3 - for 1, 2 or 3
      defects, and 4 for higher numbers). Altogether, 196 kidney images were evaluated.
      The assessment was performed independently by 2 observers: A - an experienced
      specialist in nuclear medicine, who evaluated the images twice, and B - a
      resident physician with limited experience in the field. RESULTS: The agreement
      between the two evaluations by the specialist (intra-observer test) reached a
      level of 96% for conventional images and 90% for the parametric ones. In the
      inter-observer test, full agreement reached the levels of 84% and 71% for
      conventional and parametric images, respectively. If +/- 1 degree of the image
      score was taken as factual agreement, the intra-observer concordance reached
      100%, and for inter-observer comparison, the agreement reached 99% and 97% for
      conventional and parametric images, respectively. CONCLUSIONS: The concordance of
      image assessment for conventional and parametric images is very good. In
      observations by two physicians, a somewhat closer agreement was reached for
      conventional than for parametric images; the difference between the two series of
      image assessments was small.

PMID- 19173185
TI  - Optimized lymphoscintigraphy and diagnostics of lymphatic oedema of the lower
      extremities.
AB  - BACKGROUND: The elementary diagnostic method for the detection of lymph
      circulation abnormalities in extremities is lymphoscintigraphy. This method
      provides information on the morphology and function of the lymphatic system.
      However, there are no generally acceptable standards for lymphoscintigraphy,
      which makes judgment of its clinical usefulness very difficult. MATERIAL AND
      METHODS: In this work, a discussion is presented on the usefulness of static
      qualitative scintigraphy of the lymphatic system of lower extremities as well as
      of its quantitative interpretation, depending upon: (1) time measurement of
      radiopharmaceutical transport in the system, and (2) assessment of its regional
      uptake in lymph nodes. The effectiveness of visual assessment combined with each
      of the quantitative evaluations mentioned is also presented. RESULTS/CONCLUSIONS:
      Combination of visual evaluation of static scintigraphy with each of the listed
      quantitative procedures improves the sensitivity of lymphoscintigraphy in the
      diagnosis of lymphatic oedema of lower extremities without affecting the
      specificity of visual evaluation. Both combined methods are characterized by
      similar indices of diagnostic efficacy. This enables limitation of the
      quantitative evaluation of lymphatic scintigraphy to the measurement of the final
      uptake of RPh in the inguinal lymphatic nodes.

PMID- 19173186
TI  - Iodine-123 uptake in vertebral haemangiomas in a patient with papillary thyroid
      carcinoma.
AB  - We present a case of a 58-year-old woman with papillary carcinoma of the thyroid
      and elevated thyroglobulin. Whole body 123I scan with SPECT images demonstrated
      focal uptake in the thoracic spine, reported as bone metastases. Subsequent
      (18)FDG PET and (99m)Tc HDP bone were normal. MRI and CT scans confirmed the
      presence of vertebral haemangiomas corresponding to the uptake seen on the (123)I
      scan. False-positive uptake of (123)I in benign vertebral haemangiomas should be
      considered in the differential diagnosis of focal vertebral uptake.

PMID- 19173187
TI  - Pulmonary emboli and extramedullary haematopoiesis in beta-thalassaemia
      intermedia.
AB  - We present a case of a 52-year-old woman with beta-thalassaemia intermedia under
      investigation for pulmonary hypertension. V/Q scan demonstrated bilateral
      pulmonary emboli. In addition there was evidence of central, posterior matched
      defects. CT pulmonary angiogram confirmed the presence of extramedullary
      haematopoiesis (EMH) in the paravertebral region. Although a few case reports of
      pulmonary emboli in thalassaemia intermedia have been published, to the best of
      our knowledge there have been no reports of matched defects caused by
      extramedullary haematopoiesis. This may be mistaken for enlarged pulmonary
      arteries, which are also seen in patients with pulmonary hypertension.

PMID- 19173188
TI  - A rare combination of cardiopulmonary anomalies demonstrated on ventilation
      perfusion scan.
AB  - In this case report we describe an unusual appearance seen on a ventilation
      perfusion (V/Q) scan in a woman with pulmonary hypertension. Although the
      pulmonary hypertension was not caused by pulmonary emboli, the V/Q scan suggested
      several cardiac anomalies which may lead to pulmonary hypertension. Most of the
      cardiac anomalies, including right-sided aortic arch and right-to-left shunt, can
      be deduced from careful examination of the V/Q scan. A subsequent cardiac MRI
      scan confirmed the anomalies.

PMID- 19173189
TI  - [Role of C-C chemokines in the determination of pleural effusion etiology].
AB  - INTRODUCTION: Pleural effusion secondary to various diseases is associated with
      the presence of different inflammatory cells. The C-C chemokines (MCP-1 and MIP
      1alpha), produced by pleural mesothelial cells, plays an important role in the
      recruitment of inflammatory cells to the pleural space. The purpose of the study
      was to evaluate predictive value of MCP-1 and MIP-1alpha in the differential
      diagnosis of pleural effusion. MATERIAL AND METHODS: Based on Light's criteria in
      29 cases exudates and in 10 transudates were recognized. We investigated 39
      patients with pleural effusion (congestive heart failure - 10, parapneumonic -
      11, tuberculous - 6, malignant - 12). The C-C chemokines MCP-1 and MIP-1alpha
      levels in pleural effusion and serum were measured by ELISA. RESULTS: The MCP-1
      was significantly higher (p = 0.009) in the patient with exudates than in
      patients with transudates (2436 pg/ml and 794 pg/ml respectively). ROC curve
      analysis revealed however that this parameter has limited value in the
      differentiation of exudates an transudates (MCP-1 cut off value 1060 pg/ml,
      sensitivity 48%, specificity 90%, PPV 93%, NPV 37%). The chemokine MIP-1alpha
      were significantly higher (p = 0.001) in tuberculous than in the malignant
      effusion (405 pg/ml and 30 pg/ml respectively). Based on the ROC curve analysis,
      as a cut off value in the differentiation of tuberculous and malignant pleural
      effusion a value 120 pg/ml was accepted. The sensitivity of this test was 66% and
      specificity 99%, PPV 80%, NPV 84%. CONCLUSIONS: The chemokine MCP-1 has a limited
      value in the differentiation between transudate and exudates; MIP-1alpha could be
      helpful in the differentiation between tuberculous and malignant pleural
      effusion.

PMID- 19173190
TI  - [Quality of spirometric measurements in children younger than 10 years of age in
      the light of the recommendations].
AB  - INTRODUCTION: In 2005 the European Respiratory Society/American Thoracic Society
      (ERS/ATS) published an updated document on the standardization of spirometry
      (European Respiratory Journal 2005; 26: 319-338). It defines criteria for the
      acceptability of spirometric measurements. The aim of this retrospective study
      was to assess the adherence to those standards of flow-volume measurements in
      children younger than 10 years of age. MATERIAL AND METHODS: The analysis was
      carried out on the results obtained from 233 children aged 4.2-10 years, referred
      to a spirometric lab during a period of three months. RESULTS: 116 children (all
      but one preschool) did not cooperate; the results of the 117 who completed the
      procedure of flow-volume measurement were analysed using ERS/ATS criteria. 80.3%
      of the children had back extrapolated volume (Vbe) within the defined limit, but
      only 23.9% had forced expiratory time > 3 s. FEV(1) and FVC were repeatable in
      78.6% of the children. When these three criteria were used together, the
      measurements were acceptable according to ATS/ERS recommendations in 17.1% of the
      children. Elimination of the forced expiratory time criterion has further
      increased their number to 63.2%. CONCLUSIONS: Specific recommendations for
      children should be developed, as the current requirements appear too restrictive,
      especially regarding the time of forced expiration.

PMID- 19173191
TI  - [Comparison of outpatient and inpatient costs of moderate and severe
      exacerbations of chronic obstructive pulmonary disease in Poland].
AB  - INTRODUCTION: The aim of the study was to examine the direct and indirect costs
      of COPD exacerbations under usual clinical practice in primary and secondary care
      from a societal perspective in Poland. MATERIAL AND METHODS: An observational,
      prospective study was conducted among patients with exacerbation of moderate or
      severe COPD. Seventy-three patients were included in the study - 39 treated in
      hospital (HC) and 34 treated in ambulatory care (AC). The direct costs included
      the cost of drugs, diagnostic tests, in-hospital and outpatient care. The
      indirect costs included costs of transportation to the health-care provider and
      work days lost. RESULTS: The mean duration of COPD exacerbation did not differ
      significantly between the groups [HC: 11.2 (CI 95%: 9.6-12.8) days; AC: 10.8 (CI
      95%: 9.1-12.1); p > 0.05]. The total health-care cost per exacerbation was EUR
      1197 (4137.9 PLN) in secondary care (the HC group), and it was 6 times higher
      than the total cost of exacerbation in primary care (the AC group) - EUR 199.8
      (446.9 PLN). The costs of drugs and diagnostic tests were significantly higher in
      the HC group than in the AC group; however, it was the cost of in-hospital stay
      and medical visits in the HC group that most influenced expenditure related to
      COPD exacerbations, as they were 27 times higher than in the AC group.
      CONCLUSIONS: In Poland the costs of COPD exacerbation managed in secondary care
      are 6-fold higher than in primary care. Therefore, the decisions about admission
      of patients with COPD exacerbation to hospital should be made carefully.

PMID- 19173192
TI  - [The role of interleukin-18 in the pathogenesis of bronchial asthma and other
      allergic diseases and in activation of basophils and mastocytes].
AB  - Interleukin-18 is a proinflammatory cytokine produced by a wide range of cells
      and is involved in the pathogenesis of several inflammatory diseases such as
      atopic asthma. It was recently demonstrated that IL-18 acts on T cells to induce
      airway inflammation and airway hyperresponsiveness. These observations strongly
      indicate that IL-18 stimulates Th1 cells to produce cytokines and chemokines
      responsible for the airway infiltration and inflammatory responsiveness. Moreover
      IL-18 activates mast cells and basophils playing the important role in atopy.
      Atopic asthma is characterized by eosinophilic airway inflammation, remodeling,
      mucus hypersecretion and high serum levels of IgE. Most current data suggest that
      asthma drives development of a Th2 lymphocyte-predominant immune response, which
      is associated with atopy and IgE mediated inflammation via pathways involving the
      production of proinflammatory cytokines such as IL-18. Here we discuss the
      functional role of IL-18 in activation of mast cells and basophils and
      pathogenesis of allergic diseases.

PMID- 19173193
TI  - [Bronchopulmonary dysplasia -- early and long-term pulmonary sequelae].
AB  - Improvement in perinatal care have resulted in significantly increased survival
      of premature infants. Discontinuation of correct intrauterine lung development
      and a necessity of oxygen-therapy and/or mechanical ventilation become a reason
      of bronchopulmonary dysplasia (BPD). In the first period of life the main
      complaint of these patients is oxygen dependence. Moreover the risk of serious
      infections of lower respiratory tract (particularly RSV) increases. This becomes
      the reason of readmission of about 50% prematures with diagnosed BPD in the first
      year of life. The main problem of these patients is airway obstruction, which
      very often doesn't respond to brochodilatators. The probable reason of these
      disturbances is imperfect development of respiratory system and remodelling of
      respiratory tract. Reduction in lung function (reduced FEV(1), PEF, FVC) persists
      until adolescence. Acceleration of the decrease in FEV(1)/FVC ratio may suggest
      that these patients are a risk group of COPD development. The assessment of lung
      radiography at the age of 11 years of former prematures with diagnosed BPD
      reveals the presence of persistent emphysematic changes (86% of these children
      had one or more bubbles). Abnormalities in chest high resolution CT occur in the
      majority of these patients (in 81.3% of the 10-years-olds group and in 92.5% of
      18-year-olds group). Further prospective long-term study of prematures is
      essential for the establishment of remote prognosis and treatment standards.

PMID- 19173194
TI  - [The new diagnostic methods of latent tuberculosis infection].
AB  - So far the only method of diagnostic assessment of tubercle bacillus infection
      was a skin tuberculin reaction - but it has low specificity and sensitivity. The
      article discusses the new tests in the diagnosis of a latent phase of
      tuberculosis infection and the active form of the disease based on the
      measurement of interferon gamma (IFN-gamma) released by lymphocyte T after the
      stimulation by antigens which are specific for M. tuberculosis: ESAT-6, CFP-10.
      The sensitivity and specificity of QuantiFERON-TB Gold and T-SPOT.TB tests in
      diagnosis of infection as well as in active form of disease, comparison between
      the results of tuberculin skin test and the results obtained by the new tests,
      and problem of incompatibility of results obtained thanks to those tests are
      discussed.

PMID- 19173195
TI  - [Long-term remission after erlotinib therapy in an elderly patient with advanced
      non-small-cell lung cancer. Case report and conclusions for clinical practice].
AB  - Small molecule tyrosine kinase inhibitors (TKIs) of epidermal growth factor
      receptor (EGFR) - gefitinib and erlotinib - have recently been used as a
      therapeutic option in advanced non-small cell lung cancer (NSCLC) patients
      relapsing after first- or second-line chemotherapy. We report here a case of long
      term remission in an elderly, non-smoking woman with advanced NSCLC after
      chemotherapy failure, who was selected for erlotinib therapy using demographic
      and clinical criteria. Based on this example and on the literature data we
      discuss the need for careful patient selection for this new therapeutic method.

PMID- 19173196
TI  - [Usefulness of the scintigraphic assessment of the thoracic splenosis -- a case
      report].
AB  - Thoracic splenosis of the left lung and upper abdominal area was described. Left
      minithoracotomy was performed due to unclear results from a fine needle biopsy
      and following the suggestion to obtain a tissue sample. Clinical findings were
      similar to neoplasmatic disease; intraoperative extension of the disease was
      larger than CT view and correlated with postoperative assessment with (99m)Tc
      sulphur colloid. This confirmed the usefulness of scintigraphic assessment in
      preoperative diagnosis in order to avoid thoracotomy in such cases.

PMID- 19173197
TI  - [Commentary to the article of A. Dubaniewicz and G. Moszkowska: "Analysis of
      occurrence of DRB and DQ alleles in sarcoidosis and tuberculosis from Northern
      Poland"].

PMID- 19173198
TI  - [Commentary to the article of A. Semik-Orzech, A. Barczyk and W. Pierzchala: "The
      influence of sensitivity to fungal allergens on the development and course of
      allergic diseases of the respiratory tract"].

PMID- 19173199
TI  - [Commentary to the article of K. Kruczak and E. Nizankowska-Mogilnicka: "The new
      diagnostic methods of latent tuberculosis infection"].

PMID- 19173200
TI  - [Coding in pediatric neurology: a good indicator of the quality of health care].

PMID- 19173201
TI  - [Coding in neuropediatrics based on the International Classification Diseases,
      9th revision (ICD-9), 5th edition (2006)].
AB  - AIMS: To analyze International Classification Diseases, 9th revision (ICD-9)
      coding and adapt it, on a consensus basis, to 'reasons for medical consultation',
      'diagnoses' and 'procedures' in child neurology. MATERIALS AND METHODS: The most
      frequent reasons for medical consultation, diagnoses and procedures in
      neuropediatrics were selected and assigned the most appropriate ICD-9, Clinical
      Modification (5th ed.) (ICD-9-CM) codes in accordance with this system's coding
      rules. Disorders were grouped by sections, and allocated to the various members
      of the working group (13 child neurologists from 10 hospitals in Madrid and
      environs). RESULTS: Available on the web www.neurologia.com/cie-9. ICD-9-CM codes
      were assigned to: 158 reasons for medical consultation; 886 diagnoses; 73
      diagnostic procedures; and 53 therapeutic procedures. In every case, the most
      appropriate ICD-9 code was sought for the respective diagnosis. No codes were
      invented but the working group did take certain liberties with interpretation,
      which nevertheless showed respect for general ICD-9-CM philosophy and are
      described in full in the text. CONCLUSIONS: The creation of this ICD-9 adaptation
      will not only enhance diagnostic coding in child neurology departments, but will
      also provide them with a useful tool for setting up databases to enable
      information to be retrospectively analyzed and shared by the different health
      centers.

PMID- 19173202
TI  - [Incidence of strokes in Spain: the Iberictus study. Data from the pilot study].
AB  - INTRODUCTION: In a population-based study of the incidence of stroke conducted on
      a broad denominator, it is wise first to carry out a pilot study. AIM: To present
      the results of the pilot phase of the study on stroke incidence in Spain,
      entitled Iberictus. PATIENTS AND METHODS: Population of the study: all cases
      involving the first episode of acute cerebrovascular disease (stroke or transient
      ischaemic attack) diagnosed among residents over 17 years of age with their
      habitual place of abode registered in the areas of study between 15th and 31st
      October 2005 (total denominator: 1,440,997 inhabitants). SOURCE OF DATA:
      prospective, hospital records (basic minimum data set, discharge abstracts) and
      casualty department registers. Standardised definitions: diagnostic
      categorisation and pathological, topographical and aetiological classification.
      Inter-observer agreement analysis among researchers (kappa). RESULTS: A total of
      128 cases were identified. Age range, 37-103 years; mean age, 75.7 +/- 13.4
      years; 54% were females. In all, 71.1% of the cases were collected by means of a
      basic minimum data set. There were 91 ischaemic events (29.7% atherothrombotic
      and 29.7% cardioembolic). Of the 15 haemorrhagic strokes, 40% due to arterial
      hypertension, six were lobar hemispheric, six were deep basal ganglia, and there
      were three cerebellar haemorrhages. The incidence of stroke was seen to increase
      exponentially with age. Inter-observer agreement was good for the classifications
      that were employed (range of kappa indices, 0.57-0.78). Several problems were
      detected and corrected in the fieldwork. CONCLUSIONS: The Iberictus pilot study
      yielded data that were consistent with the literature and provided us with the
      opportunity to detect and correct issues that would hinder us from conducting the
      main study.

PMID- 19173203
TI  - [Identifying deletions in the dystrophin gene and detecting carriers in families
      with Duchenne's/Becker's muscular dystrophy].
AB  - INTRODUCTION: Between 60 and 65% of the mutations that cause Duchenne's/Becker's
      muscular dystrophy (DMD/BMD) are deletions in the dystrophin gene. Identifying
      deletions confirms the diagnosis and allows carriers to be detected with
      precision, which is the main preventive resource. The frequency and distribution
      of deletions in the DMD gene is unknown in south-east Mexico. AIMS: To identify
      deletions in the DMD gene and to detect carriers in families with DMD/BMD in
      south-east Mexico. PATIENTS AND METHODS: The study involved 26 families that
      showed clinical signs of DMD/BMD: Deletions were determined in the DNA of 40
      males by means of the multiple polymerase chain reaction (PCR) in 22 segments of
      the gene. Detection of carriers was applied to 33 female relatives using PCR
      restriction fragment length polymorphism of the polymorphic markers Pert 87.8/Taq
      1, pERT 87.15/Bam H1, and single PCR for VNTR MP1P by linkage analysis. RESULTS:
      Deletions were identified in 67.5% of patients with DMD and they were located in
      the 5' end and in the central region, exons 44 to 52, of the gene. In the
      detection of carriers, 73.33% of the families were informative. The markers
      87.8/Taq 1 and MPIP yielded the greatest information power, with 26.67 and
      33.33%, respectively. Of a total of 33 females, 21 (63.64%) were carriers, one
      (3.03%) was a non-carrier and 11 (33.33%) were not informative. CONCLUSIONS: The
      frequency of deletions was 67.5%. Carrier status was determined in 66.67% of the
      females who were analysed. The markers pERT 87.8/Taq 1 and MP1P yielded the
      greatest information power.

PMID- 19173204
TI  - [Clinical course of multiple sclerosis in patients treated with cytostatic drugs
      for cancer].
AB  - INTRODUCTION: The risk of side effects secondary to global and non-specific
      immune suppression has limited the systematic application of immunosuppressive
      therapy in multiple sclerosis (MS). However, when a patient with MS develops a
      cancer, cytostatic drugs as treatment for the neoplastic process may induce
      improvement not only of the cancer but also of MS. CASE REPORTS: We present a
      series of four women with clinically defined MS and subjected to cytostatic
      therapy (cisplatin, 5-fluorouracil, leukovorin, adriamycin, tamoxifen and
      anastrozole) after the development of cancer: two presented breast cancer, one
      colon cancer, and the fourth parotid gland malignancy. Their clinical and
      neuroimaging course is described, following chemotherapy for the malignant
      disease. None of the patients have suffered further MS outbreaks. The four women
      have improved and remain clinically stable after neoplastic treatment. Magnetic
      resonance imaging showed persistence of the same lesion burden in three patients,
      and reduction in the other. At the present one patient receives weekly
      intramuscular interferon-beta 1a, whereas the other did not received any
      treatment. CONCLUSIONS: Probably there are no specific cytostatics for MS.
      Immunosuppressive therapy could be a therapeutic option among patients with an
      aggressive clinical course.

PMID- 19173205
TI  - [Huntington's disease: molecular foundations and implications in the
      characterisation of the neuronal mechanisms responsible for linguistic
      processing].
AB  - INTRODUCTION: Certain neuronal models of linguistic processing suggest that the
      basal ganglia play a key role in this processing, thanks to their integration
      within the so-called cortico-striato-cortical circuits. DEVELOPMENT: A
      comparative analysis, at a phenotypic and molecular level, of the pathologies,
      syndromes and disorders that entail a structural alteration and/or a dysfunction
      of the basal ganglia is essential for validating and optimising such models, as
      well as for achieving a suitable characterisation of the genetic program
      responsible for the development and functioning of the 'language organ'. One of
      the most significant pathologies in this respect is Huntington's disease, which
      is caused by the destruction of certain groups of neurons in the caudate nucleus.
      CONCLUSIONS: This type of analysis seems to confirm the hypothesis that, during
      linguistic processing, the basal ganglia would be responsible for planning and
      modulating the sequential tasks related to the so-called procedural (or
      computational or rule-applying) component of language. Equally plausible,
      however, is the hypothesis that, inside them, there would be regions that are
      specifically dedicated to processing the different (morphological and
      syntactical) rules that go to make up said component. Additionally, the nature of
      these subcortical structures and the function they perform would explain the
      simultaneous presence of an articulatory and a linguistic deficit in disorders in
      which the basal ganglia are affected. Lastly, this kind of analysis is also
      making it possible to characterise some of the genes that constitute the genetic
      program responsible for the development and functioning of this region of the
      brain and, by extension, of the 'language organ'.

PMID- 19173206
TI  - [Neuro-ophthalmological manifestations of pituitary adenomas. The usefulness of
      optical coherence tomography].
AB  - INTRODUCTION: Pituitary adenomas are a frequently occurring pathology that
      require multidisciplinary management by several different specialists. Their
      neuro-ophthalmological manifestations vary widely and sometimes appear as the
      presenting symptom. AIM: To gather the main ophthalmological signs and symptoms
      of these tumours so that specialists who find themselves before any of them will
      suspect this pathology. DEVELOPMENT: This survey was based on the clinical
      experience of the neuro-ophthalmological unit at the Hospital Clinic de
      Barcelona, with over 350 patients who had suffered from pituitary tumours. A
      bibliographical search was also carried out on Medline for papers published on
      pituitary adenomas in the literature in both English and Spanish. We focused
      mainly on those that reported on the ophthalmological manifestations of such
      tumours. A number of articles were found dealing with isolated ophthalmological
      manifestations of these tumours, many of them as presenting symptoms. We also
      found review articles in English. Apart from oculomotor disorders and other less
      common findings, visual field defects stand out as the guiding symptom of this
      condition. CONCLUSIONS: Improved diagnostic techniques are allowing pituitary
      tumours to be detected at increasingly earlier stages, but cases are still seen
      with neuro-ophthalmological symptoms as the presenting symptoms. Familiarity with
      these syndromes is crucial. In addition to the clinical and visual field
      examination, optical coherence tomography is particularly useful for the
      diagnosis and follow-up of these patients. Prospective studies are needed to
      establish factors for predicting the visual recovery in these patients.

PMID- 19173207
TI  - [Mixed meningoencephalitis caused by Mycobacterium tuberculosis and varicella
      zoster virus].

PMID- 19173209
TI  - [Tumoral pituitary apoplexy and cocaine consumption].

PMID- 19173210
TI  - [Pseudomigraine with pleocytosis: a pediatric case with cerebellar ataxia and
      mumps virus infection].

PMID- 19173211
TI  - [Reversible posterior leukoencephalopathy syndrome caused by pre-eclampsia].

PMID- 19173212
TI  - [Adie syndrome and chronic nephropathy].

PMID- 19173213
TI  - [HaNDL syndrome and Hashimoto encephalopathy. Reply].

PMID- 19173214
TI  - Fluorescent benzofurazan-cholic acid conjugates for in vitro assessment of bile
      acid uptake and its modulation by drugs.
AB  - One of the most common mechanisms of hepatotoxicity is drug-induced cholestasis.
      Hence, new approaches for screening the cholestatic potential of drug candidates
      are desirable. In this context, we describe herein the use of synthetic 4
      nitrobenzo-2-oxa-1,3-diazole (NBD) fluorescent conjugates of cholic acid (ChA) at
      positions 3alpha, 3beta, 7alpha, and 7beta for in vitro assessment of bile acid
      uptake. All the conjugates show a strong absorption band between 400 and 550 nm
      and have a fluorescence quantum yield of approximately 0.45, with an emission
      maximum centered at approximately 530 nm. After their photophysical
      characterization, 3alpha-, 3beta-, 7alpha-, and 7beta-NBD-ChA were used to
      monitor uptake in freshly isolated rat hepatocytes by means of a previously
      optimized flow cytometry technique. Transport of the cholic acid derivatives
      inside the cell was detected and quantified by measuring the increase of NBD
      green fluorescence within cells over time. The effect of troglitazone, a well
      known inhibitor of bile acid uptake by the sodium taurocholate co-transporting
      polypeptide, supports the specificity of fluorescent NBD-ChA transport. According
      to the final intracellular fluorescence level attained and the uptake rate,
      3alpha-NBD-ChA was found to be the most efficient derivative. Furthermore, sodium
      valproate, cyclosporin A, and chlorpromazine decreased the uptake of 3alpha-NBD
      ChA, in agreement with their relative in vivo potency as cholestatic compounds;
      in contrast, sodium citrate (the negative control) had no effect. These results
      support the suitability of the in vitro flow cytometric assay with NBD-ChA to
      detect compounds that affect bile acid uptake.

PMID- 19173215
TI  - Glycosylated neurotensin analogues exhibit sub-picomolar anticonvulsant potency
      in a pharmacoresistant model of epilepsy.
AB  - Neurotensin (NT) is an endogenous neuropeptide involved in a variety of central
      and peripheral neuromodulatory effects. Herein we show the effects of site
      specific glycosylation on the in vitro and in vivo pharmacological properties of
      this neuropeptide. NT analogues containing O-linked disaccharides (beta-melibiose
      and alpha-TF antigen) or beta-lactose units linked by a PEG(3) spacer were
      designed and chemically synthesized using Fmoc chemistry. For the latter
      analogue, Fmoc-Glu-(beta-Lac-PEG(3)-amide) was prepared. Our results indicate
      that the addition of the disaccharides does not negatively affect the sub
      nanomolar affinity or the low-nanomolar agonist potency for the neurotensin
      receptor subtype 1 (NTS1). Interestingly, three glycosylated analogues exhibited
      sub-picomolar potency in the 6 Hz limbic seizure mouse model of pharmacoresistant
      epilepsy following intracerebroventricular administration. Our results suggest
      for the first time that chemically modified NT analogues may lead to novel
      antiepileptic therapies.

PMID- 19173216
TI  - Total synthesis of (-)-spirangien A, an antimitotic polyketide isolated from the
      myxobacterium Sorangium cellulosum.
AB  - An expedient first total synthesis of (-)-spirangien A, a potent cytotoxic and
      antifungal polyketide of myxobacterial origin, is described. By using a common
      1,3-diol intermediate obtained by an efficient aldol-reduction sequence for
      installation of the C15-C18 and C25-C28 stereotetrads and a reagent-controlled
      boron aldol coupling followed by spiroacetalization, a highly convergent strategy
      was developed for construction of the elaborate spiroacetal core. Conversion of
      this advanced spiroacetal intermediate into (+)-spirangien diene, obtained
      previously by controlled degradation of spirangien A, was then achieved by
      installation of the truncated side-chain using an allylboration-Peterson
      sequence. The total synthesis of (-)-spirangien A was then achieved by the
      controlled attachment of the unsaturated C1-C12 side-chain, avoiding exposure to
      light. A Stork-Wittig olefination and double Stille cross-coupling sequence was
      exploited to install the delicate conjugated pentaene chromophore featuring
      alternating (Z)- and (E)-olefins, leading initially to the methyl ester of
      spirangien A, which proved significantly more stable than the corresponding free
      acid. Subsequent careful hydrolysis afforded (-)-spirangien A, validating the
      relative and absolute configuration.

PMID- 19173217
TI  - Experimental study of the bone marrow protective effect of a traditional Chinese
      compound preparation.
AB  - This study investigated the effect of Wei Gan Li on bone marrow haemopoiesis in
      myelosuppressed anaemic mice induced by (60)Cogamma, cyclophosphamide and
      chloramphenicol. After treatment with Wei Gan Li, colony forming units of
      granulocyte macrophages, erythroid cells, burst forming unit-erythroid cells,
      megakaryocytes and the proliferation of bone marrow stromal cells were measured
      by in vitro cell culture techniques. Bone marrow haemopoietic stem cells were
      measured by flow cytometry. The peripheral blood cell count was found to have
      significantly recovered after Wei Gan Li administration and the proliferation of
      bone marrow haemopoietic stem/progenitor cells and BMSC were also significantly
      increased. Wei Gan Li was therefore found to promote the recovery of bone marrow
      haemopoietic function in myelosuppressed anaemic mice.

PMID- 19173218
TI  - Photodynamic effect of hypericin in primary cultures of human umbilical
      endothelial cells and glioma cell lines.
AB  - Hypericin is the most powerful naturally occurring photosensitizer and as such
      there is renaissant interest in the potentials of this compound for anticancer
      photodynamic therapy (PDT). The purpose of this study was to investigate the
      hypericin-mediated photodynamic therapy effects on normal human umbilical
      endothelial cells (HUVECs) in comparison with cancer human glioma cell lines U-87
      MG and U-373 MG, in in vitro conditions. The data suggest that endothelial cells
      as well as glioma cell lines are sensitive only to photoactivated hypericin. The
      inhibitory effects of photoactivated hypericin did not differ in endothelial
      compared with tumor cells in cytotoxicity MTT and DNA fragmentation assays.
      However, an important difference in sensitivity was found between the above
      mentioned cell types in migration and metalloproteinases inhibition assays
      performed as cell function tests. The findings in both function tests were
      supported by the high sensitivity of endothelial cells in an additional
      angiogenesis test of tubular formation in vitro.

PMID- 19173219
TI  - Isolation and identification of hemostatic ingredients from Lamiophlomis rotata
      (Benth.) Kudo.
AB  - Lamiophlomis rotata (Benth.) Kudo (LR) is a traditional drug used by Chinese
      minorities such as Tibetans, Mongolians and Na Xi with the beneficial effects of
      hemostasis and alleviating pain. Flavonoids ingredients (P(1)), iridoid
      glycosides ingredients (P(2)) and maximus polarity components ingredients (P(3))
      were isolated from the aqueous extract of LR (AELR) with polyamide and
      macroporous adsorptive resins chromatographic columns. The hemostatic activity of
      these ingredients was estimated by the changes in bleeding time (BT), clotting
      time (CT) and blood coagulation parameters in mice or rats. RP-HPLC was used to
      analyze the chemical composition of P(2). As a result, AELR and P(2)
      significantly shortened BT, CT and thrombin time (TT), and increased fibrinogen
      (FIB), but P(1) and P(3) showed no hemostatic effect during the experiment.
      Moreover, P(2) showed satisfactory hemostatic effect with dose-effect
      relationship and low toxicity in mice. 8-Dehydroxy shanzhiside, phloyoside II,
      shanzhiside methylester, loganin, and 8-O-acetylshanzhiside methylester were
      detected as the main iridoid glycosides in P(2) by RP-HPLC. Our results suggest
      that iridoid glycosides may be the hemostatic activity ingredients of L. rotata
      and are a potential hemostatic medicine.

PMID- 19173220
TI  - Anti-allergic activity of principles from the roots and heartwood of Caesalpinia
      sappan on antigen-induced beta-hexosaminidase release.
AB  - The dichloromethane extract of the roots and heartwood of Caesalpinia sappan
      exhibited potent inhibitory activity against beta-hexosaminidase release as
      marker of degranulation in rat basophilic leukemic (RBL-2H3) cells, with
      inhibition of 98.7% and 87.5% at concentration of 100 microg/ml, respectively.
      These extracts were further separated by chromatographic techniques to give two
      chalcones and seven homoisoflavones. Among the compounds tested, sappanchalcone
      (2) possessed the most potent effect against allergic reaction in RBL-2H3 cells
      with an inhibitory concentration (IC50) value of 7.6 microM, followed by 3
      deoxysappanchalcone (1, IC50 = 15.3 microM), whereas other compounds showed
      moderate and mild effects. The results suggested the following structural
      requirements of chalcones (1 and 2) and homoisoflavones (3-9) for anti-allergic
      activity: (i) chalcone exhibited higher activity than homoisoflavone (ii) vicinal
      hydroxylation at B-ring of chalcone conferred higher activity than one
      hydroxylation; and (iii) for homoisoflavone, the hydroxyl groups at C-3 and C-4
      positions decreased the activity. This is the first report of C. sappan for anti
      allergic activity.

PMID- 19173222
TI  - Selection and structural analysis of de novo proteins from an alpha3beta3 genetic
      library.
AB  - The construction of novel functional proteins has been a key area of protein
      engineering. However, there are few reports of functional proteins constructed
      from artificial scaffolds. Here, we have constructed a genetic library encoding
      alpha3beta3 de novo proteins to generate novel scaffolds in smaller size using a
      binary combination of simplified hydrophobic and hydrophilic amino acid sets. To
      screen for folded de novo proteins, we used a GFP-based screening system and
      successfully obtained the proteins from the colonies emitting the very bright
      fluorescence as a similar intensity of GFP. Proteins isolated from the very
      bright colonies (vTAJ) and bright colonies (wTAJ) were analyzed by circular
      dichroism (CD), 8-anilino-1-naphthalenesulfonate (ANS) binding assay, and
      analytical size-exclusion chromatography (SEC). CD studies revealed that vTAJ and
      wTAJ proteins had both alpha-helix and beta-sheet structures with thermal
      stabilities. Moreover, the selected proteins demonstrated a variety of
      association states existing as monomer, dimer, and oligomer formation. The SEC
      and ANS binding assays revealed that vTAJ proteins tend to be a characteristic of
      the folded protein, but not in a molten-globule state. A vTAJ protein, vTAJ13,
      which has a packed globular structure and exists as a monomer, was further
      analyzed by nuclear magnetic resonance. NOE connectivities between backbone
      signals of vTAJ13 suggested that the protein contains three alpha-helices and
      three beta-strands as intended by its design. Thus, it would appear that
      artificially generated alpha3beta3 de novo proteins isolated from very bright
      colonies using the GFP fusion system exhibit excellent properties similar to
      folded proteins and would be available as artificial scaffolds to generate
      functional proteins with catalytic and ligand binding properties.

PMID- 19173223
TI  - Matrix-free detection of intact ions from proteins in argon-cluster secondary ion
      mass spectrometry.
AB  - In the secondary ion mass spectrometry (SIMS) of organic substances, the
      molecular weight of the intact ions currently detectable is at best only as high
      as 1000 Da, which for all practical purposes prevents the technique from being
      applied to biomaterials of higher mass. We have developed SIMS instrumentation in
      which the primary ions were argon cluster ions having a kinetic energy per atom,
      controlled down to 1 eV. On applying this instrumentation to several peptides and
      proteins, the signal intensity of fragment ions was decreased by a factor of
      10(2) when the kinetic energy per atom was decreased below 5 eV; moreover, intact
      ions of insulin (molecular weight (MW): 5808) and cytochrome C (MW: 12 327) were
      detected without using any matrix. These results indicate that fragmentation can
      be substantially suppressed without sacrificing the sputter yield of intact ions
      when the kinetic energy per atom is decreased to the level of the target's
      dissociation energy. This principle is fully applicable to other biomolecules,
      and it can thus be expected to contribute to applications of SIMS to biomaterials
      in the future.

PMID- 19173221
TI  - Dynamics of a truncated prion protein, PrP(113-231), from (15)N NMR relaxation:
      order parameters calculated and slow conformational fluctuations localized to a
      distinct region.
AB  - Prion diseases are associated with the misfolding of the prion protein (PrP(C))
      from a largely alpha-helical isoform to a beta-sheet rich oligomer (PrP(Sc)).
      Flexibility of the polypeptide could contribute to the ability of PrP(C) to
      undergo the conformational rearrangement during PrP(C)-PrP(Sc) interactions,
      which then leads to the misfolded isoform. We have therefore examined the
      molecular motions of mouse PrP(C), residues 113-231, in solution, using (15)N NMR
      relaxation measurements. A truncated fragment has been used to eliminate the
      effect of the 90-residue unstructured tail of PrP(C) so the dynamics of the
      structured domain can be studied in isolation. (15)N longitudinal (T(1)) and
      transverse relaxation (T(2)) times as well as the proton-nitrogen nuclear
      Overhauser effects have been used to calculate the spectral density at three
      frequencies, 0, omega(N,) and 0.87omega(H). Spectral densities at each residue
      indicate various time-scale motions of the main-chain. Even within the structured
      domain of PrP(C), a diverse range of motions are observed. We find that removal
      of the tail increases T(2) relaxation times significantly indicating that the
      tail is responsible for shortening of T(2) times in full-length PrP(C). The
      truncated fragment of PrP has facilitated the determination of meaningful order
      parameters (S(2)) from the relaxation data and shows for the first time that all
      three helices in PrP(C) have similar rigidity. Slow conformational fluctuations
      of mouse PrP(C) are localized to a distinct region that involves residues 171 and
      172. Interestingly, residues 170-175 have been identified as a segment within PrP
      that will form a steric zipper, believed to be the fundamental amyloid unit. The
      flexibility within these residues could facilitate the PrP(C)-PrP(Sc) recognition
      process during fibril elongation.

PMID- 19173225
TI  - Memory-related changes in L-citrulline and agmatine in the rat brain.
AB  - L-citrulline, L-ornithine, and agmatine are the metabolites of L-arginine by
      nitric oxide synthase (NOS), arginase, and arginine decarboxylase (ADC),
      respectively. In contrast to the NOS and arginase pathways, the role of the ADC
      agmatine pathway in learning and memory has only been paid attention lately.
      Recent evidence suggests a potential involvement of agmatine in learning and
      memory processing. The present study further addressed this issue by comparing
      the levels of agmatine, as well as L-arginine, L-citrulline, and L-ornithine, in
      the hippocampus, parahippocampal region, prefrontal cortex, vestibular nucleus,
      and cerebellum in rats that were trained in the delayed nonmatch to position task
      in the T-maze with their yoked controls. There were significantly increased
      agmatine levels in the prefrontal, entorhinal, and perirhinal cortices and
      increased L-citrulline concentrations in the dentate gyrus (DG) and prefrontal
      cortex in the T-maze training group relative to the control one. L-arginine and L
      ornithine levels were not significantly different between groups in the brain
      regions examined. These results demonstrate T-maze training-induced region
      specific increases in L-citrulline and agmatine. Significant positive
      correlations between prefrontal and perirhinal agmatine levels and animals'
      performance in the T-maze further suggest the direct involvement of agmatine in
      learning and memory processing.

PMID- 19173226
TI  - Vasoactive intestinal peptide acts via multiple signal pathways to regulate
      hippocampal NMDA receptors and synaptic transmission.
AB  - Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide, which belongs to
      a superfamily of structurally related peptide hormones including pituitary
      adenylate cyclase-activating polypeptide (PACAP). Although several studies have
      identified the involvement of PACAP in learning and memory, little work has been
      done to investigate such a role for VIP. At least three receptors for VIP have
      been identified including the PACAP receptor (PAC1-R) and the two VIP receptors
      (VPAC receptors). VIP can activate the PAC1-R only if it is used at relatively
      high concentrations (e.g., 100 nM); however, at lower concentrations (e.g., 1 nM)
      it is selective for the VPAC receptors. Our lab has showed that PAC1-R activation
      signals through PKC/CAKbeta/Src pathway to regulate NMDA receptors; however,
      there is little known about the potential regulation of NMDA receptors by VPAC
      receptors. Our studies demonstrated that application of 1 nM VIP enhanced NMDA
      currents by stimulating the VPAC receptors as the effect was blocked by VPAC
      receptor antagonist [Ac-Tyr(1), D-Phe(2)]GRF (1-29). This enhancement of NMDA
      currents was blocked by both Rp-cAMPS and PKI(14-22) (they are highly specific
      PKA inhibitors), but not by the specific PKC inhibitor, bisindolylmaleimide I. In
      addition, the VIP-induced enhancement of NMDA currents was accentuated by
      inhibition of phosphodiesterase 4, which inhibits the degradation of cAMP. This
      regulation of NMDA receptors also required the scaffolding protein AKAP. In
      contrast, the potentiation induced by high concentration of VIP (e.g., 100 nM)
      was mediated by PAC1-R as well as by Src kinase. Overall, these results show that
      VIP can regulate NMDA receptors through different receptors and signaling
      pathways.

PMID- 19173228
TI  - Neural bases of autobiographical support for episodic recollection of faces.
AB  - Incidental retrieval of autobiographical knowledge can provide rich contextual
      support for episodic recollection of a recent event. We examined the neural bases
      of these two processes by performing fMRI scanning during a recognition memory
      test for faces that were unfamiliar, famous, or personally known. The presence of
      pre-experimental knowledge of a face was incidental to the task, but nonetheless
      resulted in improved performance. Two distinct networks of activation were
      associated with correct recollection of a face's prior presentation (recollection
      hits vs. correct rejections) on one hand, and with pre-experimental knowledge
      about it (famous or personally known vs. unfamiliar faces) on the other. The
      former included mid/posterior cingulate cortex, precuneus, and ventral striatum.
      The latter included bilateral hippocampus, retrosplenial, and ventromedial
      prefrontal cortices. Anterior and medial thalamic activations showed an
      interaction between both effects, driven by increased activation for recollection
      of unfamiliar faces. When recollecting the presentation of a famous or personally
      known face, hippocampal activation increased with participants' ratings of how
      well they felt they knew the person shown. Ventromedial prefrontal cortex showed
      significantly greater activation for personally known than famous faces. Our
      results indicate a dissociation between the involvement of retrosplenial vs.
      mid/posterior cingulate and precuneus in memory tasks. They also indicate that,
      during recognition memory experiments, the hippocampus supports incidental
      retrieval of pre-experimental knowledge about the stimuli presented. This type of
      knowledge likely underlies the additional recollection found for prior
      presentation of well known stimuli compared with novel ones and may link
      hippocampal activation at encoding to subsequent memory performance more
      generally.

PMID- 19173229
TI  - Transvaginal ultrasound measurement of cervical length in the supine and upright
      positions versus Bishop score in predicting successful induction of labor at
      term.
AB  - OBJECTIVES: To examine the predictive value of cervical length as measured by
      transvaginal sonography (TVS) in supine and upright maternal positions for the
      mode of delivery and induction-to-delivery interval after induction of labor at
      term, and to compare these measurements with the Bishop score and its predictive
      value. METHODS: TVS for cervical length measurement in the supine and upright
      positions and digital examination of the cervix were performed in 68 nulliparous
      and 34 parous women before induction of labor at term. In assessing the
      predictive value of the Bishop score and TVS parameters for a vaginal delivery
      after labor induction only nulliparous women were included in the analysis, since
      all the parous women delivered vaginally. Both nulliparous and parous women were
      included in the analysis of the induction-to-delivery interval. The method of
      labor induction, oxytocin or prostaglandin, was determined on the basis of the
      pre-induction Bishop score. RESULTS: Logistic regression analysis showed in
      nulliparous women that only the cervical length measured in the upright position
      was a significant predictor of the need for Cesarean section (odds ratio 1.14;
      95% CI, 1.02-1.27). The areas under the receiver-operating characteristics curve
      in predicting the need for Cesarean section because of failure to progress were
      higher for the cervical length, both in supine and upright positions, than for
      the Bishop score (0.66, 0.68 and 0.46, respectively). Only the Bishop score
      correlated significantly with the induction-to-delivery interval in both
      nulliparous and parous women. However, this may have been due to a selection
      bias, as no significant correlation with Bishop score was found when the oxytocin
      and prostaglandin induction-to-delivery intervals were analyzed separately.
      CONCLUSION: Our results suggest that maternal postural change might improve the
      accuracy of sonographically-measured cervical length for predicting a vaginal
      delivery after induction of labor at term. However, our results need to be
      confirmed in a larger and more homogeneous population.

PMID- 19173230
TI  - Fetoscopic release of umbilical cord amniotic band in a human fetus.
AB  - Umbilical cord amniotic bands occur in approximately 10% of cases of amniotic
      band syndrome and are a well-known cause of fetal death. An unexpected amniotic
      band encircling the umbilical cord was diagnosed during a fetoscopic procedure to
      release a leg constriction. Both bands were released fetoscopically using a YAG
      laser. We report the first case of an amniotic band involving the umbilical cord
      diagnosed and released prenatally.

PMID- 19173232
TI  - Calculating patient-specific risk for Down syndrome: does software matter?

PMID- 19173233
TI  - How should the obstetrician respond to surrogate pregnancy?

PMID- 19173234
TI  - Effect of a low-lying placenta on delivery outcome.
AB  - OBJECTIVES: To evaluate delivery outcome in pregnancies with a low-lying placenta
      (within 2 cm of, but not covering, the internal os) that had been identified
      within 4 weeks of delivery. We examined the likelihood of a vaginal delivery and
      investigated the clinical significance of the placental edge to internal os
      measurement. METHODS: A retrospective chart review was performed for singleton
      pregnancies delivering in the third trimester with a low-lying placenta
      identified within 4 weeks of delivery. Outcome variables included type of
      delivery, maternal and neonatal hemoglobin levels, and umbilical artery pH
      levels. RESULTS: Eighty-six patients met the study criteria of a low-lying
      placenta identified within 4 weeks of delivery. Forty-five of these patients were
      allowed to labor and, of these, 29 (64.4%) delivered vaginally. The vaginal
      delivery rate was 76.5% in patients with a placenta to cervical os distance of 1
      2 cm, significantly greater than the rate of 27.3% in patients in whom the
      placenta was within 1 cm of the cervix (P = 0.0085). A maternal hemoglobin level
      below 8.0 g/dL was the most common morbidity associated with low-lying placenta.
      Analysis of morbidity observed did not clearly favor either elective Cesarean
      delivery or attempted vaginal delivery. CONCLUSIONS: In this retrospective study,
      most laboring patients with a low-lying placenta were able to have a vaginal
      delivery with limited morbidity. The likelihood of a vaginal delivery was greater
      with increased placenta to cervical os distance. Further studies are needed to
      determine the clinical significance of the placenta to cervical os distance and
      the interval from scan to delivery.

PMID- 19173235
TI  - Cervical length and risk of antepartum bleeding in women with complete placenta
      previa.
AB  - OBJECTIVE: To evaluate if cervical length predicts prepartum bleeding and
      emergency Cesarean section in cases of placenta previa. METHODS: Between
      September 2005 and September 2007, cervical length was measured by transvaginal
      ultrasound in women with complete placenta previa persisting into the third
      trimester of pregnancy. A complete follow-up of pregnancy was obtained in all
      cases. RESULTS: Overall, 59 women were included in the study group. The mean +/-
      SD gestational age at ultrasound was 30.7 +/- 2.7 weeks and the cervical length
      was 36.9 +/- 8.8 mm. Cesarean delivery was performed in all cases, at a mean
      gestational age of 34.7 +/- 2.3 weeks. Twenty-nine (49.1%) of the women presented
      prepartum bleeding and 12 (20.3%) required an emergency Cesarean section prior to
      34 completed weeks due to massive hemorrhage. Cervical length did not differ
      significantly between cases with and those without prepartum bleeding (35.3 +/-
      9.3 mm vs. 38.4 +/- 8.2 mm; P = 0.18), but was significantly shorter among
      patients who underwent emergency Cesarean section < 34 weeks due to massive
      hemorrhage compared with patients who underwent elective Cesarean section (29.4
      +/- 5.7 mm vs. 38.8 +/- 8.5 mm; P = 0.0006). CONCLUSIONS: Transvaginal
      sonographic cervical length predicts the risk of emergency Cesarean section < 34
      weeks in women with complete placenta previa.

PMID- 19173236
TI  - Multimodality imaging findings of leiomyomatosis peritonealis disseminata.

PMID- 19173237
TI  - Four-dimensional ultrasonographic imaging of fetal lower urinary tract
      obstruction and guidance of percutaneous cystoscopy.

PMID- 19173238
TI  - Is the location of cord entanglement associated with antepartum death in
      monoamniotic twins?

PMID- 19173239
TI  - Role of three-dimensional power Doppler in the antenatal diagnosis of placenta
      accreta: comparison with gray-scale and color Doppler techniques.
AB  - OBJECTIVE: To assess the role of three-dimensional (3D) power Doppler in the
      antenatal diagnosis of placenta accreta and compare its diagnostic performance
      with gray-scale and color Doppler ultrasonography. METHODS: One hundred and
      seventy pregnant women with persistent placenta previa totalis (after 28 weeks'
      gestation) were prospectively enrolled into this study. Gray-scale transabdominal
      ultrasound examination was performed to detect loss of the subendometrial
      echolucent zone and other abnormalities suggestive of placenta accreta. Color
      flow mapping was used to scan the whole placenta to detect any newly formed
      vessels at the serosa-bladder border or the presence of abnormal lacunae. Finally
      a targeted examination of angioarchitecture in the basal and lateral views of the
      placenta was carried out using 3D power Doppler. The ultrasound findings were
      analyzed with reference to the final diagnosis made during Cesarean delivery.
      RESULTS: Placenta accreta and its variants (including increta and percreta) were
      confirmed in 39 patients at the time of Cesarean delivery. Based on receiver
      operating characteristics analysis, 'numerous coherent vessels' visualized using
      3D power Doppler in the basal view was the best single criterion for the
      diagnosis of placenta accreta, with a sensitivity of 97% and a specificity of
      92%. If we considered the presence of at least one criterion to be diagnostic
      when using each ultrasound technique, then 3D power Doppler would have the best
      positive predictive value (76%), followed by gray-scale (51%) and color Doppler
      (47%). The majority of patients with placenta accreta showed multiple
      characteristic features on ultrasound imaging. In contrast, those patients with a
      false-positive diagnosis (i.e. the final diagnosis was placenta previa alone)
      tended to show isolated ultrasound markers of the condition. CONCLUSION: 3D power
      Doppler may be useful as a complementary technique for the antenatal diagnosis or
      exclusion of placenta accreta.

PMID- 19173240
TI  - First-trimester maternal serum tumor necrosis factor receptor-1 and pre
      eclampsia.
AB  - OBJECTIVES: To examine whether the maternal serum concentration of the soluble
      receptor-1 of tumor necrosis factor-alpha (TNF-R1) at 11-13 weeks of gestation in
      pregnancies that subsequently develop pre-eclampsia is different from that in
      women without this complication. METHODS: The concentration of TNF-R1 at 11 + 0
      to 13 + 6 weeks was measured in samples from 128 cases that subsequently
      developed pre-eclampsia and 569 controls with no pregnancy complications. TNF-R1
      and uterine artery pulsatility index (UtA-PI) values were expressed as multiples
      of the median (MoM) adjusted for maternal factors. The distributions of log TNF
      R1 MoM and log UtA-PI MoM in the control and pre-eclampsia groups were compared.
      Logistic regression analysis was used to determine whether a significant
      contribution is provided by maternal factors, TNF-R1 and UtA-PI in predicting pre
      eclampsia. The performance of screening was determined by analysis of receiver
      operating characteristics curves. RESULTS: Median TNF-R1 and UtA-PI were
      significantly higher in the pre-eclampsia group (TNF-R1, 1.062 MoM; UtA-PI, 1.301
      MoM) than in the control group (TNF-R1, 0.996 MoM; UtA-PI, 1.037 MoM). There was
      no significant association between TNF-R1 and gestational age at delivery, birth
      weight percentile or UtA-PI. Logistic regression analysis demonstrated
      significant contributions to the detection of pre-eclampsia from maternal factors
      and UtA-PI but not from TNF-R1. CONCLUSIONS: In pregnancies developing pre
      eclampsia the maternal serum TNF-R1 concentration at 11-13 weeks of gestation is
      increased, but the level of TNF-R1 is not associated with the degree of
      impairment in placental perfusion or the severity of pre-eclampsia. Measurement
      of serum TNF-R1 does not improve the prediction of pre-eclampsia provided by
      screening based on a combination of maternal factors and UtA-PI.

PMID- 19173241
TI  - Maintaining quality assurance for sonographic nuchal translucency measurement:
      lessons from the FASTER Trial.
AB  - OBJECTIVE: To evaluate nuchal translucency measurement quality assurance
      techniques in a large-scale study. METHODS: From 1999 to 2001, unselected
      patients with singleton gestations between 10 + 3 weeks and 13 + 6 weeks were
      recruited from 15 centers. Sonographic nuchal translucency measurement was
      performed by trained technicians. Four levels of quality assurance were employed:
      (1) a standardized protocol utilized by each sonographer; (2) local-image review
      by a second sonographer; (3) central-image scoring by a single physician; and (4)
      epidemiological monitoring of all accepted nuchal translucency measurements cross
      sectionally and over time. RESULTS: Detailed quality assessment was available for
      37 018 patients. Nuchal translucency measurement was successful in 96.3% of
      women. Local reviewers rejected 0.8% of images, and the single central physician
      reviewer rejected a further 2.9%. Multivariate analysis indicated that higher
      body mass index, earlier gestational age and transvaginal probe use were
      predictors of failure of nuchal translucency measurement and central image
      rejection (P = 0.001). Epidemiological monitoring identified a drift in
      measurements over time. CONCLUSION: Despite initial training and continuous image
      review, changes in nuchal translucency measurements occur over time. To maintain
      screening accuracy, ongoing quality assessment is needed.

PMID- 19173242
TI  - Second-trimester genetic sonogram for detection of fetal chromosomal
      abnormalities in a community-based antenatal testing unit.
AB  - OBJECTIVE: To evaluate the efficacy of the second-trimester genetic sonogram for
      the detection of Down syndrome and other chromosomal abnormalities in a community
      based antenatal testing unit. METHODS: This was a retrospective study using data
      from two community hospital antenatal ultrasound units. Six hundred and sixty
      fetal ultrasound examinations in both at-risk (n = 581) and low-risk (n = 79)
      pregnancies were performed from 15 + 0 to 22 + 6 weeks' gestation and all cases
      were verified for outcome data. The sonographic detection of a major congenital
      anomaly or a sonographic marker (increased nuchal skinfold, short humerus, short
      femur, echogenic bowel, pyelectasis, echogenic intracardiac focus, absence or
      hypoplasia of fifth mid phalanx or choroid plexus cyst) was recorded. The entire
      group of 660 ultrasound examinations as well as subgroups with and without non
      ultrasound risk factors for a fetal chromosomal abnormality were analyzed to
      determine the sensitivity, specificity, positive and negative predictive values
      and positive likelihood ratio for the detection of Down syndrome and other fetal
      chromosomal abnormalities. RESULTS: There were 32 (4.85%) chromosomal
      abnormalities in our study population. Twelve (3.75%) of these were Down
      syndrome, of which eight (66.6%) had a positive ultrasound examination in the
      second trimester. Six of seven (85.7%) of the trisomy 18 fetuses, 2/2 of the
      trisomy 13 fetuses and 2/3 of the non-mosaic 45,X fetuses had positive sonograms.
      The overall detection rate for chromosomal abnormalities was 20/32 (sensitivity,
      62.5%; specificity, 80.7%; negative predictive value, 97.7%; positive predictive
      value, 14.2%; positive likelihood ratio, 3.24). Major structural defects and
      sonographic markers, excluding hypoplastic fifth digit and choroid plexus cyst,
      occurred significantly more frequently in Down syndrome cases compared with
      normal ones. CONCLUSIONS: In a community-based antenatal testing unit we have
      demonstrated a detection rate for fetal Down syndrome with the second-trimester
      genetic sonogram that is comparable to the range of sensitivities reported by
      larger centers involving primarily high-risk patients. However, only 12 of the 32
      fetal chromosomal abnormalities that we encountered were Down syndrome.

PMID- 19173244
TI  - The arterial anatomy of the Achilles tendon: anatomical study and clinical
      implications.
AB  - The Achilles tendon is the most frequently ruptured tendon in the lower limb and
      accounts for almost 20% of all large tendon injuries. Despite numerous published
      studies describing its blood supply, there has been no uniformity in describing
      its topography. The current study comprises a detailed anatomical study of both
      the intrinsic and extrinsic arterial supply of the Achilles tendon, providing the
      detail sought from studies calling for improved planning of surgical procedures
      where damage to the vascularity of the Achilles tendon is likely. A dissection,
      microdissection, histological, and angiographic study was undertaken on 20
      cadaveric lower limbs from 16 fresh and four embalmed cadavers. The Achilles
      tendon is supplied by two arteries, the posterior tibial and peroneal arteries.
      Three vascular territories were identified, with the midsection supplied by the
      peroneal artery, and the proximal and distal sections supplied by the posterior
      tibial artery. The midsection of the Achilles tendon was markedly more
      hypovascular that the rest of the tendon. The Achilles tendon is at highest risk
      of rupture and surgical complications at its midsection. Individuals with
      particularly poor supply of the midsection may be at increased risk of tendon
      rupture, and approaches to the tendon operatively should consider the route of
      supply by the peroneal artery to this susceptible part of the tendon.

PMID- 19173243
TI  - Fluorinated 1,2,4-Triazolo[1,5-a]pyrimidine-6-carboxylic acid derivatives as
      antimycobacterial agents.
AB  - A series of fluorinated 1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylic acid
      derivatives was designed and synthesized as fluoroquinolone analogues. The
      synthesized compounds were screened against Mycobacterium tuberculosis H(37)R(v)
      strain at 6.25 microg/mL concentration. Compound 4, the 7-oxo-2-(trifluoromethyl)
      4,7-dihydro-1,2,4-triazolo[5,1-a]pyrimidine-6-carboxylic acid was found to be a
      very potent inhibitor, being able to inhibit 92% growth of M. tuberculosis
      H(37)R(v )at 6.25 microg/mL concentration. At the same time, it proofed to be
      nontoxic to mammalian cells (IC(50) > 62.5 microg/mL in VERO cells).

PMID- 19173245
TI  - Translation and rotation movements of the mandible during mouth opening and
      closing.
AB  - To assess the relative contribution of rotation and translation of the
      temporomandibular condyle-disc assembly during opening and closing movements,
      free movements of maximum mouth opening and closing were recorded in healthy
      subjects (12 men, 14 women) using an optoelectronic three-dimensional motion
      analyzer. For each subject, the displacement of the lower interincisal point, the
      path of the condylar reference point, the degree of rotation around the three
      orthogonal rotational axes, and the relative contribution of translation and
      rotation were calculated during all movement of mouth opening and closing. The
      distance covered by the interincisor point and the rotational angle about the
      transverse axis at maximum mouth opening were larger in men than in women, but
      the difference cancelled after correcting for mandibular radius in the sagittal
      plane; mandibular rotation was always larger than translation, but never
      approaching 100%; opening and closing translations were similar within sex, but
      their paths were longer in men than in women (P < 0.05); rotational angles around
      vertical and sagittal axes were negligible; the linear correlation between
      maximum mandibular opening and condylar translation was minor and not
      significant. In normal subjects, mouth opening and closing as modeled at the
      interincisor point was determined more by mandibular rotation than by
      translation, but in no occasion a pure rotation was found. The percentage
      rotation was not identical during mouth opening and closing; female and male
      paths were not totally coincident; no correlation between maximum mandibular
      opening and condylar translation was found.

PMID- 19173248
TI  - Three muscles in the upper costovertebral region: description and clinical
      anatomy.
AB  - The aim of the study was to describe three small muscles in the upper
      costovertebral region that have close proximity to the ventral rami of the lower
      cervical and upper two thoracic spinal nerves. The study was performed using both
      anterior and posterior approaches to the costovertebral region. Twenty-five human
      cadavers, 15 males and 10 females with a mean age of 50 years and with normal
      spines, constituted the material of the study. Dissection revealed the presence
      of three triangular muscles that extended from the transverse processes of the
      seventh cervical through second thoracic vertebrae to the upper borders of the
      necks of the first through third ribs, respectively. The second and third muscles
      are described and reported for the first time. The ventral rami of the lower
      cervical and upper two thoracic spinal nerves emerged through narrow gaps between
      the described muscles and the bodies of seventh cervical and upper two thoracic
      vertebrae, respectively. The lateral branch of the dorsal ramus of the
      corresponding spinal nerve issued posteriorly between the muscle and the
      articular capsule of the zygapophyseal joint. It then curved round the posterior
      aspect of the muscle and passed through the gap between the muscle and the
      levator costarum, after supplying them both. We suggest that these three muscles
      were suggested to share a common embryogenesis with the intertransverse muscles.
      In addition, this study suggests that the three muscles described herein could be
      one of the potential causes of thoracic outlet syndrome.

PMID- 19173249
TI  - The frequency of accessory sacroiliac joints.

PMID- 19173250
TI  - Anatomy of the petrosphenoidal and petrolingual ligaments at the petrous apex.
AB  - The petrous apex is a complex area surrounded by the cavernous sinus, Dorello's
      canal and Meckel's cave. The petrosphenoidal ligament (PSL) and the petrolingual
      ligament (PLL) are important structures located in the region. These two
      ligaments were examined under a surgical microscope in 10 specimens of five adult
      cadaveric heads fixed in formalin. They were found to span from the petrous apex
      to the posterior clinoid process, and the lingula of the sphenoid bone,
      respectively. The dural sleeve of the abducens nerve, the dorsal meningeal artery
      or its medial branch, and the venous blood space were located below the PSL in
      all specimens, and the petrous or sphenoidal insertion of the PSL varied in five
      specimens. The PLL invariably surrounded part of the dorsal and lateral walls of
      the lacerum segment of the internal carotid artery (ICA), just under the
      anteroinferior portion of the anteromedial wall of Meckel's cave in all
      specimens. The PSL and PLL are valuable anatomical landmarks for identifying the
      ICA and the nerves in this region. A thorough understanding of the relationship
      of the two ligaments with neurovascular structures is a prerequisite for surgery
      in and around the petrous apex.

PMID- 19173251
TI  - The arterial supply of the patellar tendon: anatomical study with clinical
      implications for knee surgery.
AB  - The middle-third of the patellar tendon (PT) is well-established as a potential
      graft for cruciate ligament reconstruction, but there is little anatomical basis
      for its use. Although studies on PT vascular anatomy have focused on the risk to
      tendon pedicles from surgical approaches and knee pathophysiology, the
      significance of its blood supply to grafting has not been adequately explored
      previously. This investigation explores both the intrinsic and extrinsic arterial
      anatomy of the PT, as relevant to the PT graft. Ten fresh cadaveric lower limbs
      underwent angiographic injection of the common femoral artery with radio-opaque
      lead oxide. Each tendon was carefully dissected, underwent plain radiography and
      subsequently schematically reconstructed. The PT demonstrated a well-developed
      and consistent vascularity from three main sources: antero-proximally, mainly by
      the inferior-lateral genicular artery; antero-distally via a choke-anastomotic
      arch between the anterior tibial recurrent and inferior medial genicular
      arteries; and posteriorly via the retro-patellar anastomotic arch in Hoffa's fat
      pad. Two patterns of pedicles formed this arch: inferior-lateral and descending
      genicular arteries (Type-I); superior-lateral, inferior-lateral, and superior
      medial genicular arteries (Type-II). Both types supplied the posterior PT, with
      the majority of vessels descending to its middle-third. The middle-third PT has a
      richer intrinsic vascularity, which may enhance its ingrowth as a graft, and
      supports its conventional use in cruciate ligament reconstruction. The pedicles
      supplying the PT are endangered during procedures where Hoffa's fat pad is
      removed including certain techniques of PT harvest and total knee arthroplasty.

PMID- 19173252
TI  - You live on.

PMID- 19173253
TI  - The clinical anatomy of the anterolateral abdominal wall musculature.
AB  - The anatomy of the anterolateral abdominal wall is mainly of interest to medical
      students early in their studies. Clinically, it is mostly relevant to surgeons
      who are performing laparotomies and repairing or preventing hernias. The author's
      life-long experience suggests that some of the lesser-known details of the
      anatomy of the abdominal wall have been neglected resulting in some suboptimal
      results. This manuscript highlights some of these details which, hopefully, will
      lead to improved outcomes for patients.

PMID- 19173254
TI  - Diploic venous anatomy studied in-vivo by MRI.
AB  - Calvarial diploic venous anatomy has been studied post-mortem, but few studies
      have addressed these venous structures in-vivo. Previous work in our laboratory
      has shown that intraosseous infusion through the skull diploic space near the
      diploic veins in animals and humans does access the superior sagittal sinus and
      the systemic venous system. We developed a volumetric method of imaging the
      diploic veins in-vivo using MRI, intravenous gadolinium, and digital subtraction
      to provide for three-dimensional depiction and exact localization of these veins.
      We hypothesized that this technique would allow for an assessment of the
      probability of existence, distribution, and concentration of diploic veins in the
      skull. We scanned 31 neurosurgical patients, and were able to create 3D diploic
      venous maps in 74% of them. These maps were processed using Adobe Photoshop CS2.
      Mathworks MatLab 6.5, once customized, counted the number of pixels occupied by
      the diploic veins in the processed image. The probability of veins was highest in
      the occipital regions (100%). The inferior occipital (4.1%) and posterior
      parietal (4.1%) regions had the highest concentrations of diploic veins. Digital
      subtraction venography using a volumetric MRI sequence can demonstrate the
      diploic veins in-vivo. The inferior occipital region may be the best area for an
      intraosseous infusion device because it has the greatest likelihood of containing
      a vein and also has the highest concentration of veins.

PMID- 19173255
TI  - Anatomical variability of the lateral femoral cutaneous nerve: findings from a
      surgical series.
AB  - The lateral femoral cutaneous nerve (LFCN) is a branch of the lumbar plexus and
      supplies the skin of the lateral thigh region. This entrapment-compressive
      syndrome is named meralgia paresthetica or Roth's meralgia and depends, on a vast
      majority of cases, on the entrapment of the nerve in proximity of the inguinal
      ligament. Surgical decompression of the nerve is an option when conservative
      treatments fail and is usually performed through a 3-cm infrainguinal skin
      incision. Available data on anatomical variations of the LFCN derive from
      extensive cadaver dissections and lack many features relevant to the surgeon.
      This study was conducted to investigate anatomical details of the LFCN at the
      site of surgery for meralgia paresthetica. We reviewed retrospective data
      regarding the anatomical features of LFCN from 148 consecutive patients operated
      on for Roth's meralgia. In the majority of the cases the LFCN was a single trunk,
      deep to the thigh superficial fascia and to the inguinal ligament and coursing
      inferior-lateral to the anterior superior iliac spine. Less frequent findings
      were early nerve bifurcation, epifascial position, inferior-medial direction, and
      exit from the pelvis through an iliac bone canal. In 13 cases (8.8%) the nerve
      was not found at surgery. Anatomical variations of the LFCN must be considered at
      the time of surgery to maximize success rates and avoid nerve damage during
      surgical dissection.

PMID- 19173256
TI  - Acrel's ganglion.

PMID- 19173257
TI  - Neuroanatomy of cervical sympathetic trunk: a cadaveric study.
AB  - To reduce the risk of iatrogenic injury to sympathetic chain during anterior and
      anterolateral approaches to the cervical spine, its location has to be well
      defined and known by surgeons. We analyzed the course of sympathetic chain and
      its ganglia from C7 up to its entry into the cranial base and its relationship
      mainly with the longus colli (LC). Formalin fixed 20 human cadavers were
      dissected under operating microscope. Measurement of the dimensions of the
      ganglia, distance of the trunk to the LC, and the angles identifying the course
      of the chain were performed. Superior and inferior cervical/cervicothoracic
      ganglion were observed in all specimens, the middle cervical ganglion was
      observed in 48% of the specimens. The middle ganglion consisted of two ganglia in
      10% of the dissected sides. Forty percent of the inferior
      cervical/cervicothoracic ganglion was at the C7 level, 25% was at C7-Th1 disc
      level, and 35% was at Th1 level. Vertebral ganglion was detected in only 8% of
      the specimens. The course of the sympathetic trunk converges medially descending
      from upper cervical levels to the lower levels. Anterior surgical approach to the
      cervical spine is a commonly used procedure. Although Horner syndrome due to
      sympathetic injury is not a common sequence of cervical operations, our findings
      support the current few reports on the subject and should be useful to any
      surgeon who operates in the cervical region to avoid this uncommon complication.

PMID- 19173258
TI  - Methods to reduce formaldehyde levels of cadavers.

PMID- 19173259
TI  - Hermann Stieve's clinical-anatomical research on executed women during the "Third
      Reich".
AB  - Hermann Stieve (1886-1952) was Director of the Berlin Institute of Anatomy from
      1935 to 1952. His research on the female reproductive system is controversial, as
      some of his scientific insights derived from histological investigations on the
      genital organs of executed women. These investigations were made possible by the
      sharp increase in executions during the "Third Reich." Stieve's research was
      methodologically accurate and contributed significantly to contemporary
      scientific debates. Nevertheless, his use of the organs of execution victims,
      some of them resistance fighters, benefited from the Nazi justice system. He thus
      indirectly supported this system of injustice. The allegation, however, that
      Stieve "ordered" the death of prison inmates according to their menstrual cycle,
      appears to be incorrect. An appraisal of Stieve's research should avoid
      traditional black-and-white classifications of research during Nazi times. In our
      opinion, Stieve was neither a murderer nor a fervent Nazi. Nevertheless, his
      research results were flawed by their ethical and political context. Stieve will
      remain a somber footnote in the biographies of many execution victims.

PMID- 19173260
TI  - Morphologic variations of the prostatic utricle.
AB  - Anatomical variations of the prostatic utricle (PU) have rarely been reported
      despite an understanding of them being required for diagnosing and treating PU
      anomalies. This study was performed on 57 prostates to clarify the variations of
      this structure. Fifty prostates were dissected under a surgical microscope, five
      prostates were used for ultrasonography and dissection, and two others were
      processed for light microscopy and reconstructed into 3D models. The PU was
      classified into three types based on the location of its pouch. The most common
      type was one in which the PU projected out from between the two ejaculatory
      ducts. The site and shape of the utricular orifice were also diverse on the
      seminal colliculus, which was most commonly located on the distal three-fourths
      of the prostatic urethra. The results of this study clarified the variations in
      the anatomy of the PU and may help improve diagnosis and treatment of PU
      diseases.

PMID- 19173262
TI  - The clinical surface anatomy anomalies of the palmaris longus muscle in the Black
      African population of Zimbabwe and a proposed new testing technique.
AB  - The presence of the palmaris longus muscle (PLM) is highly variable. Rates of
      absence vary from 0.6% in the Korean population to as high as 63.9% in the
      Turkish population. The tendon of PLM may be absent on one or both forearms, may
      have duplicated tendons on one forearm or may be laterally shifted to the extent
      that the tendon of the PLM lies superficial to that of flexor carpi radialis
      muscle. Among Black American populations, in which there is usually mixed
      ancestry, rates of absence are 3.5%. Only two studies have been performed on
      Black African populations: in Republic of Congo and Uganda, and each showed
      widely differing rates of absence of 3.0% and 14.6%, respectively. In this study,
      a total of 890 Black Zimbabwean subjects in Harare aged between 8 and 13 years,
      were examined for clinical surface anatomy anomalies of the tendon of PLM. The
      results showed that the tendon of the PLM was absent unilaterally in 0.9% of the
      population, and bilaterally absent in 0.6% with an overall rate of absence of
      1.5%. Other variations noted were a laterally shifted PLM in 1.1% of subjects and
      duplicated tendons on one forearm, which was the least prevalent anomaly, in 0.2%
      of subjects. The author proposes a new technique to test the tendon of PLM, which
      combines resisted thumb abduction and resisted wrist flexion. The proposed
      technique capitalizes on the role of the PLM as an important abductor of the
      thumb.

PMID- 19173261
TI  - Efficacy of colistin-impregnated beads to prevent multidrug-resistant A.
      baumannii implant-associated osteomyelitis.
AB  - Osteomyelitis (OM) from multidrug-resistant (MDR) Acinetobacter has emerged in
      >30% of combat-related injuries in Iraq and Afghanistan. While most of these
      strains are sensitive to colistin, the drug is not available in bone void fillers
      for local high-dose delivery. To address this, we developed a mouse model with
      MDR strains isolated from wounded military personnel. In contrast to S. aureus
      OM, which is osteolytic and characterized by biofilm in necrotic bone, A.
      baumannii OM results in blastic lesions that do not contain apparent biofilm. We
      also found that mice mount a specific IgG response against three proteins (40,
      47, and 56 kDa) regardless of the strain used, suggesting that these may be
      immuno-dominant antigens. PCR for the A. baumannii-specific parC gene confirmed a
      100% infection rate with 75% of the MDR strains, and in vitro testing confirmed
      that all strains were sensitive to colistin. We also developed a real-time
      quantitative PCR (RTQ-PCR) assay that could detect as few as 10 copies of parC in
      a sample. To demonstrate the efficacy of colistin prophylaxis in this model, mice
      were treated with either parenteral colistin (0.2 mg colistinmethate i.m. for 7
      days), local colistin (PMMA bead impregnated with 1.0 mg colistin sulfate), or an
      unloaded PMMA bead control. While the parenteral colistin failed to demonstrate
      any significant effects versus the placebo, the colistin PMMA bead significantly
      reduced the infection rate such that only 29.2% of the mice had detectable levels
      of parC at 19 days (p < 0.05 vs. i.m. colistin and placebo).

PMID- 19173263
TI  - Direct evidence for the up-regulation of Vps34 regulated by PKCgamma during short
      term treatment with morphine.
AB  - In this study, we investigated whether PKCgamma could be associated with
      functional changes of vacuolar protein sorting 34 (Vps34) during morphine
      treatment using primary cultures of cerebral cortical neurons from mice. The
      immunoprecipitation analysis showed that p-PKCgamma and Vps34 are present
      together in molecular complexes. The treatment with morphine increases PKCgamma
      and Vps34 levels. Phosphorylation of PKCgamma increased Vps34 level. The
      inhibition of morphine-induced increase in PKCgamma phosphorylation reduced Vps34
      level. These results indicates that opioid receptor activation increases PKCgamma
      phosphorylation in the neurons and, in turn, upregulates Vps34 during short-term
      treatment with neurons.

PMID- 19173264
TI  - Complexity of contacts between synaptic boutons and dendritic spines in adult rat
      hippocampus: three-dimensional reconstructions from serial ultrathin sections in
      vivo.
AB  - The morphological relationship between a synapse and dendritic spine is an
      important determinant of synaptic function, and has been studied extensively with
      the electron microscope. This has revealed that the universal idea of one synapse
      per spine is no longer tenable; dendritic spines may on occasions form synapses
      with two or more axonal boutons. To elucidate the detailed structure and
      relationship of spines and their synaptic contacts in the molecular layers of the
      dentate gyrus of the adult rat, a study using 3-dimensional (3D) reconstructions
      was made from serial ultrathin sections (up to 150 sections per series), of both
      pre- and postsynaptic segments of axons and dendrites. We found that synapses
      from all unmyelinated axons examined were en passant and although most contacts
      between synapse and spine are one-to-one, all reconstructions examined contained
      both multisynaptic axonal segments, and multisynaptic spines. In the dentate
      gyrus, 3.48% mushroom spines were multisynaptic, synapsing with more than two
      axons, and 0.46% of the total population of synapses were multisynaptic. Although
      these values appear small, they actually comprise millions of contacts per cubic
      millimeter of tissue. Axonal varicosities can contact more than three dendritic
      spines originating from different dendritic branches while spines may branch with
      up to three heads, and spine heads may receive two or more synaptic contacts. Our
      data confirm the complexity of relationships between spines and synapses and show
      that a one-one relationship between synapse and spine cannot be assumed
      automatically.

PMID- 19173265
TI  - Dopamine D(2/3) receptor occupancy of apomorphine in the nonhuman primate brain-
      a comparative PET study with [11C]raclopride and [11C]MNPA.
AB  - Binding studies in vitro have demonstrated that the dopamine D2 receptor may
      exist in two affinity states for agonists. The high affinity state is thought to
      represent the functional state of the receptor and proportions might alter during
      disease. In vitro studies further indicate that agonists induce measurable D(2)
      receptor occupancy at clinically relevant concentrations but only when measured
      at the high affinity state. Recently developed PET-radioligands, such as
      [11C]MNPA, have now made it possible to directly study agonist binding in vivo.
      The aim of this study was to compare the inhibition by apomorphine of agonist and
      antagonist radioligand binding to D(2/3) receptors in vivo. A total of 36 PET
      measurements were performed with the D(2/3) antagonist [11C]raclopride or the
      D(2/3) agonist [11C]MNPA in two cynomolgus monkeys. On each study day, a baseline
      measurement was followed by two consecutive pretreatment studies with rising
      doses of apomorphine (0.01, 0.05, 0.15, 0.5, 1.0, and 3.0 mg/kg). Binding
      potential (BP(ND)) values were calculated for the striatum with cerebellum as
      reference region. Apomorphine inhibited [11C]raclopride and [11C]MNPA binding in
      a dose-dependent manner and to a similar extent. ID(50) and K(i) values were 0.26
      mg/kg and 29 ng/ml for [11C]raclopride and 0.50 mg/kg and 31 ng/ml for [11C]MNPA.
      The present observations do not support the existence of two affinity states in
      vivo. It might thus be speculated that all D(2/3) receptors are in the high
      affinity state at in vivo conditions.

PMID- 19173267
TI  - Total synthesis of azithromycin.
AB  - The quaternary king: Azithromycin (1), which has improved pharmacological
      profiles compared with erythromycins, was the target of an enantioselective
      synthesis. All the stereogenic quaternary carbon centers were elaborated by a
      desymmetrization of 2-substituted glycerols using a chiral imine/CuCl(2)
      catalyst.

PMID- 19173266
TI  - Human evidence of a supra-spinal modulating role of dopamine on pain perception.
AB  - BACKGROUND: Over the last decades, remarkable progresses have been accomplished
      regarding the understanding of the neurophysiologic and neuropharmacological
      bases of pain. A growing preclinical literature supports a role for substance P,
      endogenous opioids, glutamate, serotonin, and norepinephrine in pain perception.
      Recently, a series of studies explored the function of dopamine in pain
      perception, which we review here, while focusing on human studies. METHODS: The
      literature was screened using electronic databases. RESULTS: We found evidence
      from genetics, brain imaging, neuropsychiatry, and pharmacology of an involvement
      of dopamine in pain processing. Using positron emission tomography and molecular
      genetics, studies have been performed in healthy volunteers and patients
      suffering from chronic pain conditions, showing a key role of dopamine in pain
      perception. Moreover, abnormal pain perception has been documented in
      neuropsychiatric disorders, such as Parkinson's disease and schizophrenia, where
      dopamine has a pathophysiological role. Lastly, pharmacological studies have
      shown that dopaminergic drugs (antipsychotics, antiparkinsonian drugs, atypical
      antidepressants, psychostimulants) modify pain perception. DISCUSSION: Although
      there is growing evidence supporting a role of dopamine in pain perception, the
      mechanisms by which dopamine influences pain processing remains to be determined.
      On the basis of preliminary findings, we put forth the hypothesis that dopamine
      is involved in endogenous pain modulation systems, and further discuss the
      implications of this hypothesis for the understanding of the physiopathology of
      chronic pain disorders associated with dysfunctional endogenous pain modulation
      systems.

PMID- 19173268
TI  - Mid-IR spectroscopy and structural features of protonated carbonic acid in the
      gas phase.
AB  - An anti trihydroxycarbenium ion is revealed to be the gas-phase structure of
      protonated carbonic acid by IR multiple-photon dissociation spectroscopy (see
      picture for calculated structure and comparison of experimental and computed
      spectra). Deprotonation yields anti-H(2)CO(3) with a nominal gas-phase basicity
      of 724 kJ mol(-1).

PMID- 19173269
TI  - Linking borane with N-heterocyclic carbenes: effective hydrogen-atom donors for
      radical reactions.
AB  - Undue influence: N-heterocyclic carbenes (NHCs) were found to reduce the strength
      of the B-H bonds of borane by a surprisingly large amount upon the formation of
      NHC-BH(3) complexes. This property was exploited in the development of a suite of
      NHC-borane complexes for the reduction of xanthates in radical-mediated Barton
      McCombie-type deoxygenation reactions (see scheme). AIBN =
      azobisisobutyronitrile, Bn = benzyl.

PMID- 19173270
TI  - Near-IR remote release from assemblies of liposomes and nanoparticles.
AB  - Set free by light: Near-IR (NIR) laser-initiated remote release of fluorescent
      dye from complexes of liposome-gold-nanoparticle aggregates is demonstrated (see
      fluorescence images). Complexes of the desired size are shown to be a viable
      approach to the construction of vesicle-based drug-delivery systems with light
      triggered remote release characteristics. This opens up a new method to
      manipulate liposome-based drug-delivery systems in a biocompatible way by using
      the near-IR spectral range.

PMID- 19173271
TI  - An Ugi reaction in the total synthesis of (-)-dysibetaine.
AB  - (-)-Dysibetaine has been synthesized in 11 steps from readily available L-malic
      acid (see scheme). The key step is a unique Ugi 4-center-3-component cyclization
      reaction, where an ester group acts as the carboxylic acid component. The use of
      1,1,1,3,3,3-hexamethyldisilazane as an ammonia equivalent and a specially
      designed isocyanide leads to an expeditious synthesis.

PMID- 19173272
TI  - Thallium(I) as a coordination site protection agent: preparation of an isolable
      zero-valent nickel tris-isocyanide.
AB  - Blocking the pass: Low-valent Ni centers readily bind Tl(I) ions in a
      synthetically reversible fashion. The Tl units, in turn, serve as coordination
      site protection agents for Ni with respect to incoming Lewis basic ligands. This
      synthetic sequence allows for the isolation of a reactive zero-valent Ni tris
      isocyanide complex.

PMID- 19173273
TI  - In situ analysis of the Zn(S,O) buffer layer preparation for chalcopyrite solar
      cells by Zn L-edge X-ray absorption spectroscopy.
AB  - Bridging the gap between high-vacuum soft X-ray absorption spectroscopy and real
      systems under ambient conditions probes chemical reactions in situ during
      deposition and annealing processes. The origin of highly efficient buffer layers
      in Zn(S,O) is the complex formation between Zn(2+) and the S=C group of thiourea
      (see schematic), which allows ligand-to-metal and metal-to-ligand charge transfer
      (LMCT and MLCT).

PMID- 19173274
TI  - Characterization of supercomplex crude oil mixtures: what is really in there?
AB  - Through different windows: One major obstacle in energy research is the
      complexity and variety of compounds present in crude oil. A study of different
      ionization methods for mass spectrometry shows that the mass spectrum very
      strongly depends on which method is used.

PMID- 19173275
TI  - Water splitting by light with osmocene as photocatalyst.
AB  - Last but not least: A simple molecular redox system is used to split water into
      hydrogen and oxygen photochemically. Two separate photolyses are combined to a
      cyclic process (see scheme). Osmocene ([Cp(2)Os(II)] with Cp(-) = C(5)H(5)(-))
      serves as photocatalyst.

PMID- 19173276
TI  - Reversible sigma-borane-to-borylene transformation: a little something for
      everyone.
AB  - A reaction with many facets: The facile dehydrogenative synthesis of a borylene
      complex (left in scheme) from a dihydroborane (right), proceeds reversibly at
      room-temperature. The implications of this reaction for the fields of inorganic,
      main-group, and hydrogen-storage chemistry are covered in this Highlight.

PMID- 19173277
TI  - Differential microRNA expression between hepatitis B and hepatitis C leading
      disease progression to hepatocellular carcinoma.
AB  - MicroRNA (miRNA) plays an important role in the pathology of various diseases,
      including infection and cancer. Using real-time polymerase chain reaction, we
      measured the expression of 188 miRNAs in liver tissues obtained from 12 patients
      with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and 14
      patients with hepatitis C virus (HCV)-related HCC, including background liver
      tissues and normal liver tissues obtained from nine patients. Global gene
      expression in the same tissues was analyzed via complementary DNA microarray to
      examine whether the differentially expressed miRNAs could regulate their target
      genes. Detailed analysis of the differentially expressed miRNA revealed two types
      of miRNA, one associated with HBV and HCV infections (n = 19), the other with the
      stage of liver disease (n = 31). Pathway analysis of targeted genes using
      infection-associated miRNAs revealed that the pathways related to cell death, DNA
      damage, recombination, and signal transduction were activated in HBV-infected
      liver, and those related to immune response, antigen presentation, cell cycle,
      proteasome, and lipid metabolism were activated in HCV-infected liver. The
      differences in the expression of infection-associated miRNAs in the liver
      correlated significantly with those observed in Huh7.5 cells in which infectious
      HBV or HCV clones replicated. Out of the 31 miRNAs associated with disease state,
      17 were down-regulated in HCC, which up-regulated cancer-associated pathways such
      as cell cycle, adhesion, proteolysis, transcription, and translation; 6 miRNAs
      were up-regulated in HCC, which down-regulated anti-tumor immune response.
      CONCLUSION: miRNAs are important mediators of HBV and HCV infection as well as
      liver disease progression, and therefore could be potential therapeutic target
      molecules.

PMID- 19173278
TI  - Study on the pharmacokinetics drug-drug interaction potential of Glycyrrhiza
      uralensis, a traditional Chinese medicine, with lidocaine in rats.
AB  - Drug-drug interaction potentials of an herbal medicine named Glycyrrhiza
      uralensis was investigated in rats via in vitro and in vivo pharmacokinetic
      studies. P(450) levels and the metabolic rate of lidocaine in the liver
      microsomes prepared from different treatment groups were measured. In a separate
      in vivo pharmacokinetic study, the pharmacokinetic parameters of lidocaine in
      plasma and urine were estimated. P(450) levels in the rats pretreated by
      Glycyrrhiza uralensis were significant higher than that in the non-treatment
      control. The increase in P(450) levels was dose-dependent. Glycyrrhiza uralensis
      (1 and 3 g/kg) increased P(450) levels by 62% and 91%, respectively, compared
      with the non-treatment control (0.695 nmol/mg protein). The metabolic rate of
      lidocaine in the liver microsomes was significantly higher in the herb pretreated
      rats. The pharmacokinetic profile of lidocaine was significantly modified in the
      rats with the herbal pretreatment. Elimination half-lives were shortened by 39%,
      and total clearances were increased by 59% with the pretreatment of Glycyrrhiza
      uralensis. In conclusion, Glycyrrhiza uralensis showed induction effect on P(450)
      isozymes. Efficacy and safety profiles of a drug may be affected when the herbal
      products or herbal prescriptions containing the plant medicine were concomitantly
      used.

PMID- 19173279
TI  - Antioxidative effects of curcumin and its analogues against the free-radical
      induced peroxidation of linoleic acid in micelles.
AB  - Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, 1) is a
      yellow ingredient isolated from turmeric (curcumin longa). Many health benefits
      have been claimed for curcumin, and these have generally been ascribed to its
      radical-trapping antioxidant properties. In order to find more active
      antioxidants with 1 as the lead compound, we synthesized curcumin analogues,
      i.e., 1,7-bis(3,4-dihydroxyphenyl)-1,6-heptadiene-3,5-dione (2), 1-(3,4
      dihydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (3), 1-(4
      hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (4), 1,7
      bis (4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (5), 1,7-bis(3,4-dimethoxyphenyl)
      1,6-heptadiene-3,5-dione (6), 1,7-bis(4-methoxyphenyl)-1,6-heptadiene-3,5-dione
      (7), and 1,7-diphenyl-1,6-heptadiene-3,5-dione (8). Antioxidative effects of
      curcumin and these analogues against the peroxidation of linoleic acid were
      studied in sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB)
      micelles. The peroxidation was initiated thermally by a water-soluble initiator
      2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), and reaction kinetics were
      monitored by the formation of linoleic acid hydroperoxides. Kinetic analysis of
      the antioxidation process demonstrates that these compounds, except 6, 7 and 8,
      are effective antioxidants in micelles by H-atom abstraction from the phenolic
      groups. Compounds 2 and 3, which bear ortho-diphenoxyl functionality, possess
      significantly higher antioxidant activity than curcumin and other analogues, and
      the 4-hydroxy-3-methoxyphenyl group also plays an important role in the
      antioxidative activity. In addition, the synergistic antioxidant effect of these
      compounds with alpha-tocopherol (vitamin E) in micelles was also studied by
      following the formation of linoleic acid hydroperoxides and the consumption of
      alpha-tocopherol. It was found that these compounds could not synergistically
      interact with alpha-tocopherol in micelles.

PMID- 19173280
TI  - Inhibition of release of inflammatory mediators in rat peritoneal mast cells and
      murine macrophages by a Chinese herbal medicine formula (RCM-102).
AB  - RCM-102 is a Chinese herbal medicine formulation derived from a formula which was
      shown to be effective in treating seasonal allergic rhinitis (SAR) in a
      randomized placebo-controlled trial. The aim of this study was to investigate the
      in vitro effect of RCM-102 on the formation of inflammatory mediators, histamine,
      prostaglandin and nitric oxide, which are known to be involved in the
      pathophysiology of SAR. The effect of RCM-102 on histamine release was tested in
      compound 48/80-stimulated rat peritoneal mast cells. The effects of RCM-102 on
      the release of NO and prostaglandins (PGE(2)) and the expression of inducible NO
      synthase (iNOS) and COX-2 were studied in lipopolysaccharide (LPS)-stimulated RAW
      264.7 cells. In rat peritoneal mast cells, RCM-102 significantly reduced the
      compound 48/80-induced histamine release. It also significantly reduced NO and
      PGE(2) production as well as the expression of COX-2 and iNOS in RAW 264.7 cells.
      These findings indicate that RCM-102 inhibits the formation of several
      allergic/inflammatory mediators and thus may be used for treating related
      conditions such as SAR. The actions of RCM-102 are likely to be contributed by
      the synergistic actions of individual herbal ingredients.

PMID- 19173281
TI  - Antiinflammatory and lipoxygenase inhibitory compounds from Vitex agnus-castus.
AB  - Several secondary metabolites, artemetin (1), casticin (2), 3,3'-dihydroxy
      5,6,7,4'-tetramethoxy flavon (3), penduletin (4), methyl 4-hydroxybenzoate (5), p
      hydroxybenzoic acid (6), methyl 3,4-dihydroxybenzoate (7), 5-hydroxy-2
      methoxybenzoic acid (8), vanillic acid (9) and 3,4-dihydroxybenzoic acid (10)
      were isolated from a folkloric medicinal plant, Vitex agnus-castus. The
      structures of compounds 1-10 were identified with the help of spectroscopic
      techniques. Compounds 3-10 were isolated for the first time from this plant.
      These compounds were screened for their antiinflammatory and lipoxygenase
      inhibitory activities. Compounds 6, 7 and 10 were found to have significant
      antiinflammatory activity in a cell-based contemporary assay, whereas compounds 1
      and 2 exhibited a potent lipoxygenase inhibition.

PMID- 19173282
TI  - Efficient eradication of hormone-resistant human prostate cancers by inactivated
      Sendai virus particle.
AB  - Hormone-refractory prostate cancer is one of the intractable human cancers in the
      world. Here, we examined the direct tumor-killing activity of inactivated Sendai
      virus particle [hemagglutinating virus of Japan envelope (HVJ-E)] through
      induction of Type I interferon (IFN) in the hormone-resistant human prostate
      cancer cell lines PC3 and DU145. Preferential binding of HVJ-E to PC3 and DU145
      over hormone-sensitive prostate cancer cell and normal prostate epithelium was
      observed, resulting in a number of fused cells. After HVJ-E treatment, a number
      of IFN-related genes were up-regulated, resulting in Type I IFN production in PC3
      cells. Then, retinoic acid-inducible gene-I (RIG-I) helicase which activates Type
      I IFN expression after Sendai virus infection was up-regulated in cancer cells
      after HVJ-E treatment. Produced IFN-alpha and -beta enhanced caspase 8 expression
      via Janus kinases/Signal Transducers and Activators of Transcription pathway,
      activated caspase 3 and induced apoptosis in cancer cells. When HVJ-E was
      directly injected into a mass of PC3 tumor cells in SCID (severe combined
      immunodeficiency) mice, a marked reduction in the bulk of each tumor mass was
      observed and 85% of the mice became tumor-free. Although co-injection of an anti
      asialo GM1 antibody with HVJ-E into each tumor mass slightly attenuated the tumor
      suppressive activity of HVJ-E, significant suppression of tumor growth was
      observed even in the presence of anti-asialo GM1 antibody. This suggests that
      natural killer cell activation made small contribution to tumor regression
      following HVJ-E treatment in hormone-resistant prostate cancer model in vivo.
      Thus, HVJ-E effectively targets hormone-resistant prostate cancer by inducing
      apoptosis in tumor cells, as well as activating anti-tumor immunity.

PMID- 19173283
TI  - Melanoma-associated chondroitin sulphate proteoglycan as a new target antigen for
      CD4+ T cells in melanoma patients.
AB  - Melanoma-associated chondroitin sulfate proteoglycan (MCSP) (also known as high
      molecular weight-melanoma-associated antigen) represents an interesting target
      antigen for cancer immunotherapy which is expressed on human melanomas and other
      tumors such as breast carcinomas, gliomas, neuroblastomas and acute leukemias.
      MCSP seems to play an important functional role in melanoma as it is involved in
      tumor cell migration, invasion and angiogenesis. In this study, we isolated
      CD4(+) T helper cells from the blood of a healthy donor, recognizing a peptide
      from the MCSP core protein presented by HLA-DBR1*1101 molecules. T cell
      reactivity against the identified peptide could be detected in the blood of
      healthy donors and melanoma patients. MCSP specific T cells from the blood of a
      patient could be readily expanded by repeated peptide stimulation and recognized
      MCSP and HLA-DR expressing tumor cells. Our findings suggest that vaccination
      against MCSP helper T cell epitopes might be a promising approach to fight
      melanoma.

PMID- 19173284
TI  - DNA fingerprinting tags novel altered chromosomal regions and identifies the
      involvement of SOX5 in the progression of prostate cancer.
AB  - Identification of genomic alterations associated with the progression of prostate
      cancer may facilitate the better understanding of the development of this highly
      variable disease. Matched normal, premalignant high-grade prostatic
      intraepithelial neoplasia and invasive prostate carcinoma cells were procured by
      laser capture microdissection (LCM) from human radical prostatectomy specimens.
      From these cells, comparative DNA fingerprints were generated by a modified PCR
      based technique called scanning of microdissected archival lesion (SMAL)-PCR.
      Recurrent polymorphic fingerprint fragments were used in tagging altered
      chromosomal regions. Altered regions were found at cytobands 1p31.3, 1q44,
      2p23.1, 3p26.3, 3q22.3, 4q22.3, 4q35.2, 5q23.2, 8q22.3, 8q24.13, 9q21.3, 9q22.32,
      10q11.21, 11p13, 12p12.1, 13q12.1, 16q12.2 and 18q21.31. Candidate genes in the
      surrounding area that may possibly harbor mutations that change normal prostatic
      cells to progress into their tumor stages were proposed. Of these fragments, a
      420 bp alteration, absent in all 26 normal samples screened, was observed in 2
      tumors. This fragment was cloned, sequenced and localized to chromosome 12p12.1.
      Within this region, candidate gene sex determining region Y-box 5 (SOX5) was
      proposed. Further studies of SOX5 in cell lines, xenografts and human prostate
      specimens, at both the RNA and protein levels, found overexpression of the gene
      in tumors. This overexpression was then subsequently found by fluorescent in situ
      hybridization to be caused by amplification of the region. In conclusion, our
      results suggest LCM coupled with SMAL-PCR DNA fingerprinting is a useful method
      for the screening and identification of chromosomal regions and genes associated
      with cancer development. Further, overexpression of SOX5 is associated with
      prostate tumor progression and early development of distant metastasis.

PMID- 19173286
TI  - Dimerization of DNA methyltransferase 1 is mediated by its regulatory domain.
AB  - DNA methylation is a major epigenetic modification and plays a crucial role in
      the regulation of gene expression. Within the family of DNA methyltransferases
      (Dnmts), Dnmt3a and 3b establish methylation marks during early development,
      while Dnmt1 maintains methylation patterns after DNA replication. The maintenance
      function of Dnmt1 is regulated by its large regulatory N-terminal domain that
      interacts with other chromatin factors and is essential for the recognition of
      hemi-methylated DNA. Gelfiltration analysis showed that purified Dnmt1 elutes at
      an apparent molecular weight corresponding to the size of a dimer. With protein
      interaction assays we could show that Dnmt1 interacts with itself through its N
      terminal regulatory domain. By deletion analysis and co-immunoprecipitations we
      mapped the dimerization domain to the targeting sequence TS that is located in
      the center of the N-terminal domain (amino acids 310-629) and was previously
      shown to mediate replication independent association with heterochromatin at
      chromocenters. Further mutational analyses suggested that the dimeric complex has
      a bipartite interaction interface and is formed in a head-to-head orientation.
      Dnmt1 dimer formation could facilitate the discrimination of hemi-methylated
      target sites as has been found for other palindromic DNA sequence recognizing
      enzymes. These results assign an additional function to the TS domain and raise
      the interesting question how these functions are spatially and temporarily co
      ordinated.

PMID- 19173287
TI  - Large genomic rearrangements and germline epimutations in Lynch syndrome.
AB  - In one-third of families fulfilling the Amsterdam criteria for hereditary
      nonpolyposis colorectal cancer/Lynch syndrome, and a majority of those not
      fulfilling these criteria point mutations in DNA mismatch repair (MMR) genes are
      not found. The role of large genomic rearrangements and germline epimutations in
      MLH1, MSH2 and MSH6 was evaluated in 2 such cohorts. All 45 index patients were
      mutation-negative by genomic sequencing and testing for a prevalent population
      specific founder mutation, and selectively lacked MMR protein expression in tumor
      tissue. Eleven patients ("research cohort") represented 11 mutation-negative
      families among 81 verified or putative Lynch syndrome families from the nation
      wide Hereditary Colorectal Cancer Registry of Finland. Thirty-four patients from
      33 families ("clinic-based cohort") represented suspected Lynch syndrome patients
      tested for MMR gene mutations in a diagnostic laboratory during 2004-2007.
      Multiplex ligation-dependent probe amplification (MLPA) and methylation-specific
      (MS)-MLPA were used to detect rearrangements and epimutations, respectively.
      Large genomic deletions occurred in 12/45 patients (27%), being present in 3/25
      (12%), 9/16 (56%) and 0/4 (0%) among index patients lacking MLH1, MSH2 or MSH6
      expression, respectively. Germline epimutations of MLH1, one of which coexisted
      with a genomic deletion, occurred in 2 patients (4%) and were accompanied by
      monoallelic expression in mRNA. Large genomic deletions (mainly MSH2) and
      germline epimutations (MLH1) together explain a significant fraction of point
      mutation-negative families suspected of Lynch syndrome and are associated with
      characteristic clinical and family features. Our findings have important
      implications in the diagnosis and management of such families.

PMID- 19173288
TI  - Fatty acid synthase is over-expressed in large aberrant crypt foci in rats
      treated with azoxymethane.
AB  - Fatty acid synthase (FAS) is over-expressed in many human cancers including
      colon. High levels of FAS expression have also been observed in a number of
      lesions that are precursors to invasive colorectal cancer. However, FAS
      expression in aberrant crypt foci (ACF), the earliest identifiable lesions in
      colon cancer development, has not been investigated. In this study, we treated
      Fisher rats with a single dose of the colon carcinogen azoxymethane then
      evaluated ACF 100 days later. We showed that large ACF (>or=4 crypts/focus) have
      a significantly higher level of immunohistochemical staining for FAS than either
      small ACF (<or=3 crypts/focus) or normal crypts. Furthermore, the severity of
      nuclear atypia in ACF was positively associated with increased expression of FAS.
      These findings suggest that the genes associated with FAS over-expression are
      activated early in the stepwise development of colon cancer, though not until the
      ACF have reached a critical size with a level of nuclear atypia indicative of
      dysplasia.

PMID- 19173289
TI  - Monoamines block kainate- and carbachol-induced gamma-oscillations but augment
      stimulus-induced gamma-oscillations in rat hippocampus in vitro.
AB  - Monoamines are implicated in a cognitive processes in a variety of brain regions,
      including the hippocampal formation, where storage and retrieval of information
      are facilitated by synchronous network activities. We have investigated the
      effects of norepinephrine, serotonin, and dopamine on carbachol-, kainate-, and
      stimulus-induced hippocampal gamma-oscillations employing combined extra- and
      intracellular recordings. Monoamines dose-dependently and reversibly suppressed
      kainate- and carbachol-induced gamma-oscillations while increasing the frequency.
      The effect of serotonin was mimicked by fenfluramine, which releases serotonin
      from presynaptic terminals. Forskolin also suppressed kainate- and carbachol
      induced gamma-oscillations. This effect was mimicked by 8-Br-cAMP and
      isoproterenol, an agonist of noradrenergic beta-receptor suggesting that the
      monoamines-mediated suppression of these oscillations could involve intracellular
      cyclic adenosine 3',5'-cyclic monophosphate (AMP). By contrast, stimulus-induced
      gamma-oscillations were dose-dependently augmented in power and duration after
      monoamines application. Intracellular recordings from pyramidal cells revealed
      that monoamines prolonged the stimulus-induced depolarization and membrane
      potential oscillations. Stimulus-induced gamma-oscillations were also suppressed
      by isoproterenol, the D1 agonist SKF-38393 forskolin, and 8-Br-cAMP. This
      suggests that the augmentation of stimulus-induced gamma-oscillations by
      monoamines involves--at least in part-different classes of cells than in case of
      carbachol- and kainate-induced gamma-oscillations.

PMID- 19173291
TI  - Indole-3-carbinol inhibits MDA-MB-231 breast cancer cell motility and induces
      stress fibers and focal adhesion formation by activation of Rho kinase activity.
AB  - Indole-3-carbinol (I3C), a phytochemical derived from cruciferous vegetables such
      as broccoli and Brussels sprouts, has potent antiproliferative effects in human
      breast cancer cells and has been shown to decrease metastatic spread of tumors in
      experimental animals. Using chemotaxis and fluorescent-bead cell motility assays,
      we demonstrated that I3C significantly decreased the in vitro migration of MDA-MB
      231 cells, a highly invasive breast cancer cell line. Immunofluorescence staining
      of the actin cytoskeleton revealed that concurrent with the loss of cell
      motility, I3C treatment significantly increased stress fiber formation.
      Furthermore, I3C induced the localization of the focal adhesion component
      vinculin and tyrosine-phosphorylated proteins to the cell periphery, which
      implicates an indole-dependent enhancement of focal adhesions within the outer
      boundary of the cells. Coimmunoprecipitation analysis of focal adhesion kinase
      demonstrated that I3C stimulated the dynamic formation of the focal adhesion
      protein complex without altering the total level of individual focal adhesion
      proteins. The RhoA-Rho kinase pathway is involved in stress fiber and focal
      adhesion formation, and I3C treatment stimulated Rho kinase enzymatic activity
      and cofilin phosphorylation, which is a downstream target of Rho kinase
      signaling, but did not increase the level of active GTP-bound RhoA. Exposure of
      MDA-MB-231 cells to the Rho kinase inhibitor Y-27632, or expression of dominant
      negative RhoA ablated the I3C induced formation of stress fibers and of
      peripheral focal adhesions. Expression of constitutively active RhoA mimicked the
      I3C effects on both processes. Taken together, our data demonstrate that I3C
      induces stress fibers and peripheral focal adhesions in a Rho kinase-dependent
      manner that leads to an inhibition of motility in human breast cancer cells.

PMID- 19173292
TI  - Homeobox gene HOPX is epigenetically silenced in human uterine endometrial cancer
      and suppresses estrogen-stimulated proliferation of cancer cells by inhibiting
      serum response factor.
AB  - HOPX (homeodomain only protein X) is a newly identified homeobox gene whose loss
      of expression has been reported for several types of neoplasm. Although we found
      most human uterine endometrial cancers (HEC) defective in HOPX expression,
      genetic mutations in the HOPX gene were undetectable. As is the case with several
      tumor suppressor genes, the promoter region of HOPX is densely methylated in HEC
      tissue samples obtained by laser capture microdissection. HOPX mRNA and protein
      levels were reduced in the majority of samples, and this correlated with
      hypermethylation of the HOPX promoter. Forced expression of HOPX resulted in a
      partial block in cell proliferation, in vivo tumorigenicity and c-fos gene
      expression in HEC and MCF7 cells in response to 17beta-estradiol (E(2))
      stimulation. Analysis of the serum response element (SRE) of c-fos gene promoter
      showed that the effect of HOPX expression is associated with inhibition of E(2)
      induced c-fos activation through the serum response factor (SRF) motif. Knockdown
      of HOPX in immortalized human endometrial cells resulted in accelerated
      proliferation. Our study indicates that transcriptional silencing of HOPX results
      from hypermethylation of the HOPpromoter, which leads to HEC development.

PMID- 19173293
TI  - DeltaNp73alpha inhibits PTEN expression in thyroid cancer cells.
AB  - DeltaNp73 is a N-terminally truncated p53 family member with a dominant negative
      function, which is upregulated in cancer. PTEN is a lipid phosphatase, which is
      involved in the attenuation of tyrosine kinase signaling. PTEN expression is
      increased by p53, and its function is blunted in several malignancies. Because in
      most of the thyroid carcinomas, DeltaNp73alpha is upregulated, whereas PTEN
      expression down regulated, we investigated whether DeltaNp73alpha may influence
      PTEN expression in this cell model. We found that DeltaNp73alpha overexpression
      in thyroid cancer cells reduces PTEN expression, whereas DeltaNp73alpha down
      regulation by siRNA increases PTEN expression. Real-time PCR indicated that
      overexpression of DeltaNp73alpha is able to reduce PTEN mRNA levels. Moreover,
      chromatin immunoprecipitation (ChIP) and luciferase assays indicated that
      DeltaNp73alpha binds to -1031-779 region of the PTEN promoter, which is a
      different site than that for p53, thereby inhibiting promoter activity.
      Interestingly, also the transcriptionally active p73 isoforms (TAp73alpha and
      TAp73beta) bound to this DNA sequence and, at variance with DeltaNp73alpha,
      stimulated PTEN promoter activity to an extent similar to that of p53. In
      accordance with its effect on PTEN protein levels, DeltaNp73alpha increased
      phospho-Akt protein content and, as a consequence, Mdm2-mediated p53 degradation.
      This effect of DeltaNp73alpha resulted in increased thyroid cancer cell
      proliferation and reduced apoptosis and was reverted by the PI3-kinase inhibitor
      LY294002, indicating the role of Akt pathway in this effect. Taken together,
      these results indicate a novel p73 regulated mechanism for PTEN expression in
      thyroid cancer cells, and that, also through this mechanism, DeltaNp73alpha
      exerts its protumorigenic effect.

PMID- 19173290
TI  - Optical tweezers experiments resolve distinct modes of DNA-protein binding.
AB  - Optical tweezers are ideally suited to perform force microscopy experiments that
      isolate a single biomolecule, which then provides multiple binding sites for
      ligands. The captured complex may be subjected to a spectrum of forces,
      inhibiting or facilitating ligand activity. In the following experiments, we
      utilize optical tweezers to characterize and quantify DNA binding of various
      ligands. High mobility group type B (HMGB) proteins, which bind to double
      stranded DNA, are shown to serve the dual purpose of stabilizing and enhancing
      the flexibility of double stranded DNA. Unusual intercalating ligands are
      observed to thread into and lengthen the double-stranded structure. Proteins
      binding to both double- and single-stranded DNA, such as the alpha polymerase
      subunit of E. coli Pol III, are characterized, and the subdomains containing the
      distinct sites responsible for binding are isolated. Finally, DNA binding of
      bacteriophage T4 and T7 single-stranded DNA (ssDNA) binding proteins is measured
      for a range of salt concentrations, illustrating a binding model for proteins
      that slide along double-stranded DNA, ultimately binding tightly to ssDNA. These
      recently developed methods quantify both the binding activity of the ligand as
      well as the mode of binding.

PMID- 19173294
TI  - Molecular imaging of glucose uptake in oral neoplasia following topical
      application of fluorescently labeled deoxy-glucose.
AB  - The clinical value of assessing tumor glucose metabolism via F-18
      fluorodeoxyglucose (FDG) PET imaging in oncology is well established; however,
      the poor spatial resolution of PET is a significant limitation especially for
      early stage lesions. An alternative technology is optical molecular imaging,
      which allows for subcellular spatial resolution and can be effectively used with
      topical contrast agents for imaging epithelial derived cancers. The goal of this
      study was to evaluate the potential of optical molecular imaging of glucose
      metabolism to aid in early detection of oral neoplasia. Fluorescently labeled
      deoxyglucose (2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D
      glucose)) was applied topically to tissue phantoms, fresh oral biopsies (n = 32)
      and resected tumors specimens (n = 2). High-resolution imaging results show that
      2-NBDG can be rapidly delivered to oral epithelium using topical application. In
      normal epithelium, the uptake of 2-NBDG is limited to basal epithelial cells. In
      contrast, high-grade dysplasia and cancers show uptake of 2-NBDG in neoplastic
      cells throughout the lesion. Following 2-NBDG labeling, the mean fluorescence
      intensity of neoplastic tissue averages 3.7 times higher than that of matched
      nonneoplastic oral biopsies in samples from 20 patients. Widefield fluorescence
      images of 8-paired oral specimens were obtained pre and postlabeling with 2-NBDG.
      Prior to labeling, neoplastic samples showed significantly lower autofluorescence
      than nonneoplastic samples. The fluorescence of neoplastic samples increased
      dramatically after labeling; the differential increase in fluorescence was on
      average 30 times higher in neoplastic samples than in normal samples. Topical
      application of 2-NBDG can therefore provide image contrast in both widefield and
      high-resolution fluorescence imaging modalities, highlighting its potential in
      early detection of oral neoplasia.

PMID- 19173295
TI  - Birth weight and childhood leukemia: a meta-analysis and review of the current
      evidence.
AB  - A growing body of evidence suggests that childhood leukemia may be initiated in
      utero when lymphoid and myeloid cells are not fully differentiated and are
      particularly susceptible to malignant transformation. A fixed effects meta
      analysis examining the association between birth weight and childhood leukemia
      was conducted including 32 studies and 16,501 cases of all types of leukemia
      (OL), 10,974 cases of acute lymphoblastic leukemia (ALL), and 1,832 cases of
      acute myeloid leukemia (AML). The odd ratios (OR) for the association of high
      birth weight with OL, ALL and AML were 1.35 (95% CI: 1.24, 1.48), 1.23 (95% CI:
      1.15, 1.32), and 1.40 (95% CI: 1.11, 1.76), respectively, compared with normal
      birth weight. Low birth weight was not associated with overall and ALL leukemia,
      but with AML (OR = 1.50; 95% CI: 1.05, 2.13). Per 1000 g increase in birth
      weight, the OR for OL was 1.18 (95% CI: 1.13, 1.23) and ALL 1.18 (95% CI: 1.12,
      1.23). The combined available evidence from observational studies suggests that
      high birth weight is associated with an increased risk of overall leukemia and
      ALL. For AML the risk may be elevated at both high and low extremes of birth
      weight, suggesting a U-shaped association.

PMID- 19173297
TI  - Selective targeting by preS1 domain of hepatitis B surface antigen conjugated
      with phosphorylcholine-based amphiphilic block copolymer micelles as a
      biocompatible, drug delivery carrier for treatment of human hepatocellular
      carcinoma with paclitaxel.
AB  - Using dithioester-capped 2-methacryloyloxyethyl phosphorylcholine (MPC) as a
      macro chain transfer agent, a diblock copolymer was synthesized with n-butyl
      methacrylate (BMA) as hydrophobic core-forming blocks. The MPC-BMA unit was
      copolymerized with an immobilizable unit, p-nitrophenylcarbonyloxyethyl
      methacrylate (NPMA). The NPMA moiety then was modified by the addition of preS1
      domain of hepatitis B surface antigen (HBsAg). This micelle-forming nanoparticle,
      the poly (MPC-co-BMA-co-NPMA) (PMBN) conjugated with preS1 enables solubilization
      of paclitaxel (PTX) with increased hepatotropism. The 50% inhibitory
      concentration (IC(50)) values of PTX and PTX/PMBN-preS1 against the human
      hepatocellular carcinoma cell line, HepG2, were 1,008 and 131 nM, respectively (p
      < 0.05). Conjugation of preS1 to PMBN enhanced strongly the synergistic
      inhibitory effect of paclitaxel on HepG2 cells in vitro, whereas such a change in
      IC(50) was not detected against the human squamous cell carcinoma cell line,
      A431. Tumor growth rates of a HepG2 xenograft in Balb/c nude mice after
      intraperitoneal injection of PTX, PTX/PMBN and PTX/PMBN-preS1 were +97.9%, -74.3%
      and -96.2%*, respectively (*p < 0.05 versus PTX). The local paclitaxel levels
      after administration of the PMBN-preS1 conjugate were determined in the
      xenografts by high-performance liquid chromatography and were 8 times higher than
      that after administration of paclitaxel alone. No side effects attributable to
      PMBN-preS1 were observed histologically in vital organs, and body weight loss was
      significantly less in the PTX/PMBN-preS1 group. These studies demonstrate that
      PMBN-preS1 may be used as a human hepatocyte-specific drug delivery carrier
      without serious adverse effects.

PMID- 19173298
TI  - How I became a biochemist.

PMID- 19173296
TI  - Regulation of deoxycholate induction of CXCL8 by the adenomatous polyposis coli
      gene in colorectal cancer.
AB  - Elevated deoxycholic acid (DCA), mutations in the adenomatous polyposis coli
      (APC) gene and chronic inflammation are associated with increased risk of
      colorectal cancer. APC status was manipulated to determine whether DCA mediates
      inflammatory molecules in normal or initiated colonic mucosa. DCA increased
      steady state mRNA and protein levels of CXCL8 in cells which do not express wild
      type APC. Steady-state CXCL8 mRNA and protein were suppressed when cells with
      conditional expression of wild-type APC were exposed to DCA. Immunostaining did
      not detect CXCL8 in normal human colonic mucosa. CXCL8 was expressed in
      adenomatous polyps and adenocarcinomas. CXCL8 expression correlated with nuclear
      beta-catenin localization in epithelial cells of adenomas, but was associated
      with endothelial cells and neutrophils in the adenocarcinomas. DCA-mediated CXCL8
      promoter-reporter activity was elevated in a mutant APC background. Wild-type APC
      suppressed this effect. Mutation of activator protein-1 (AP-1) or nuclear factor
      kappa B (NF-kappaB) sites suppressed the activation of the CXCL8 promoter
      reporter by DCA. Chromatin immunoprecipitation revealed that AP-1 and NF-kappaB
      binding to the 5'-promoter of CXCL8 was induced by DCA. The beta-catenin
      transcription factor was bound to the 5'-promoter of CXCL8 in the absence or
      presence of DCA. Phenotypic assays determined that DCA-mediated invasion was
      blocked by antibody-directed against CXCL8 or wild-type APC. CXCL8 exposure led
      to matrix metalloproteinase-2 production and increased invasion on laminin-coated
      filters. These data suggest that DCA-mediated CXCL8 occurs in initiated colonic
      epithelium and neutralizing CXCL8 could reduce the invasive potential of tumors.

PMID- 19173299
TI  - Genomic location analysis by ChIP-Seq.
AB  - The interaction of a multitude of transcription factors and other chromatin
      proteins with the genome can influence gene expression and subsequently cell
      differentiation and function. Thus systematic identification of binding targets
      of transcription factors is key to unraveling gene regulation networks. The
      recent development of ChIP-Seq has revolutionized mapping of DNA-protein
      interactions. Now protein binding can be mapped in a truly genome-wide manner
      with extremely high resolution. This review discusses ChIP-Seq technology, its
      possible pitfalls, data analysis and several early applications.

PMID- 19173300
TI  - Isoform-specific cleavage of 14-3-3 proteins in apoptotic JURL-MK1 cells.
AB  - The proteins of 14-3-3 family are substantially involved in the regulation of
      many biological processes including the apoptosis. We studied the changes in the
      expression of five 14-3-3 isoforms (beta, gamma, epsilon, tau, and zeta) during
      the apoptosis of JURL-MK1 and K562 cells. The expression level of all these
      proteins markedly decreased in relation with the apoptosis progression and all
      isoforms underwent truncation, which probably corresponds to the removal of
      several C-terminal amino acids. The observed 14-3-3 modifications were partially
      blocked by caspase-3 inhibition. In addition to caspases, a non-caspase protease
      is likely to contribute to 14-3-3's cleavage in an isoform-specific manner. While
      14-3-3 gamma seems to be cleaved mainly by caspase-3, the alternative mechanism
      is essentially involved in the case of 14-3-3 tau, and a combined effect was
      observed for the isoforms epsilon, beta, and zeta. We suggest that the processing
      of 14-3-3 proteins could form an integral part of the programmed cell death or at
      least of some apoptotic pathways.

PMID- 19173301
TI  - Loss of cell-cell contacts induces NF-kappaB via RhoA-mediated activation of
      protein kinase D1.
AB  - Cell-cell contacts mediated by cadherins are known to inhibit the small Rho
      GTPase RhoA. We here show that in epithelial cells the disruption of these cell
      cell contacts as mediated by a calcium switch leads to actin re-organization and
      the activation of RhoA. We identified the serine/threonine kinase protein kinase
      D1 (PKD1) as a downstream target for RhoA in this pathway. After disruption of
      cell-cell contacts, PKD1 relayed RhoA activation to the induction of the
      transcription factor NF-kappaB. We found that a signaling complex composed of the
      kinases ROCK, novel protein kinase C (nPKC), and Src family kinases (SFKs) is
      upstream of PKD1 and crucial for RhoA-mediated NF-kappaB activation. In
      conclusion, our data suggest a previously undescribed signaling pathway of how
      RhoA is activated by loss of cell-cell adhesions and by which it mediates the
      activation of NF-kappaB. We propose that this pathway is of relevance for
      epithelial tumor cell biology, where loss of cell-cell contacts has been
      implicated in regulating cell survival and motility.

PMID- 19173302
TI  - Secretory products from human adipocytes stimulate proinflammatory cytokine
      secretion from human endothelial cells.
AB  - Hyperplasia and hypertrophy of fat cells can be found in obesity and increased
      adiposity is associated with endothelial dysfunction as an early event of
      atherosclerosis. However, it is unclear whether human adipocytes directly
      influence endothelial protein secretion. To study the crosstalk between fat and
      endothelial cells, human umbilical venous endothelial cells (HUVECs) were
      cultured in infranatants (Adipo) of primary differentiated human adipocytes.
      Interestingly, significantly increased secretion of 23 cytokines and chemokines
      from HUVECs was detected in four independent experiments after Adipo stimulation
      by protein array analysis detecting a total of 174 different proteins. Among
      those, time-dependent Adipo-induced upregulation of cytokine secretion in HUVECs
      was confirmed by ELISA for interleukin (IL)-8, monokine induced by gamma
      interferon, macrophage inflammatory protein (MIP)-1beta, MIP-3alpha, monocyte
      chemoattractant protein-1, and IL-6. Factors besides adiponectin, leptin,
      resistin, and tumor necrosis factor alpha appear to mediate these stimulatory
      effects. Our findings suggest that endothelial cell secretion is significantly
      influenced towards a proinflammatory pattern by adipocyte-secreted factors.

PMID- 19173303
TI  - Metazoan origins of DNA replication: regulation through dynamic chromatin
      structure.
AB  - DNA replication in eukaryotes is initiated at multiple replication origins
      distributed over the entire genome, which are normally activated once per cell
      cycle. Due to the complexity of the metazoan genome, the study of metazoan
      replication origins and their activity profiles has been less advanced than in
      simpler genome systems. DNA replication in eukaryotes involves many protein
      protein and protein-DNA interactions, occurring in multiple stages. As in
      prokaryotes, control over the timing and frequency of initiation is exerted at
      the initiation site. A prerequisite for understanding the regulatory mechanisms
      of eukaryotic DNA replication is the identification and characterization of the
      cis-acting sequences that serve as replication origins and the trans-acting
      factors (proteins) that interact with them. Furthermore, in order to understand
      how DNA replication may become deregulated in malignant cells, the distinguishing
      features between normal and malignant origins of DNA replication as well as the
      proteins that interact with them must be determined. Based on advances that were
      made using simple genome model systems, several proteins involved in DNA
      replication have been identified. This review summarizes the current findings
      about metazoan origins of DNA replication and their interacting proteins as well
      as the role of chromatin structure in their regulation. Furthermore, progress in
      origin identification and isolation procedures as well as potential mechanisms to
      inhibit their activation in cancer development and progression are discussed.

PMID- 19173304
TI  - Matrilysin (MMP-7) cleaves C-type lectin domain family 3 member A (CLEC3A) on
      tumor cell surface and modulates its cell adhesion activity.
AB  - Matrilysin (MMP-7) plays important roles in tumor progression. Previous studies
      have suggested that MMP-7 binds to tumor cell surface and promotes their
      metastatic potential. In this study, we identified C-type lectin domain family 3
      member A (CLEC3A) as a membrane-bound substrate of MMP-7. Although this protein
      is known to be expressed specifically in cartilage, its message was found in
      normal breast and breast cancer tissues as well as breast and colon cancer cell
      lines. Because few studies have been done on CLEC3A, we overexpressed its
      recombinant protein in human cancer cells. CLEC3A was found in the cell membrane,
      extracellular matrix (ECM), and culture medium of the CLEC3A-expressing cells.
      CLEC3A has a basic sequence in the NH(2)-terminal domain and showed a strong
      heparin-binding activity. MMP-7 cleaved the 20-kDa CLEC3A protein, dividing it to
      a 15-kDa COOH-terminal fragment and an NH(2)-terminal fragment with the basic
      sequence. The 15-kDa fragment no longer had heparin-binding activity. Treatment
      of the CLEC3A-expressing cells with MMP-7 released the 15-kDa CLEC3A into the
      culture supernatant. Furthermore, the 20-kDa CLEC3A promoted cell adhesion to
      laminin-332 and fibronectin substrates, but this activity was abrogated by the
      cleavage by MMP-7. These results suggest that CLEC3A binds to heparan sulfate
      proteoglycans on cell surface, leading to the enhancement of cell adhesion to
      integrin ligands on ECM. It can be speculated that the cleavage of CLEC3A by MMP
      7 weakens the stable adhesion of tumor cells to the matrix and promotes their
      migration in tumor microenvironments.

PMID- 19173306
TI  - Conformational dynamics of the EGFR kinase domain reveals structural features
      involved in activation.
AB  - The epidermal growth factor receptor (EGFR) has been the focus of intensive
      studies because of its importance in cancer research. Thus, a broader
      understanding of the molecular mechanism of activation of the EGFR kinase will
      have profound significance for the development of novel therapeutics. Numerous
      crystal structures of EGFR kinase, including the structure of the activating
      kinase dimer, have provided snapshots of the specific pathway. Herein, we
      performed unrestrained-, as well as targeted-molecular dynamics simulations based
      on these data, to gain further insight into the conformational changes
      responsible for activation. Comparison of the monomer- versus activating-EGFR
      dimer simulations indicates that the dimerization is stabilizing structural
      elements associated with the activated state and predicts new salt-bridge
      interactions involving activation-loop residues that may also be associated with
      that state. Targeted molecular dynamics simulations of the inactive-to-active
      EGFR transition, as well as the reverse pathway, confirm the formation of
      conserved structural features of functional importance for the activity or
      stabilization of either conformation. Interestingly, simulations of the L834R
      mutant, which is associated with cancer, suggest that the structural basis of the
      activation induced by that mutation might be the ability of the mutated R834
      residue to consecutively form salt bridges with neighboring acidic residues and
      cause destabilization of a hydrophobic cluster in the inactive state.

PMID- 19173305
TI  - Hitting the bull's eye: novel directed cancer therapy through helicase-targeted
      synthetic lethality.
AB  - Designing strategies for anti-cancer therapy have posed a significant challenge.
      One approach has been to inhibit specific DNA repair proteins and their
      respective pathways to enhance chemotherapy and radiation therapy used to treat
      cancer patients. Synthetic lethality represents an approach that exploits pre
      existing DNA repair deficiencies in certain tumors to develop inhibitors of DNA
      repair pathways that compensate for the tumor-associated repair deficiency. Since
      helicases play critical roles in the DNA damage response and DNA repair,
      particularly in actively dividing and replicating cells, it is proposed that the
      identification and characterization of synthetic lethal relationships of DNA
      helicases will be of value in developing improved anti-cancer treatment
      strategies. In this review, we discuss this hypothesis and current evidence for
      synthetic lethal interactions of eukaryotic DNA helicases in model systems.

PMID- 19173307
TI  - Merging chemical and biological space: Structural mapping of enzyme binding
      pocket space.
AB  - Structure-based drug design tries to mutually map pharmacological space populated
      by putative target proteins onto chemical space comprising possible small
      molecule drug candidates. Both spaces are connected where proteins and ligands
      recognize each other: in the binding pockets. Therefore, it is highly relevant to
      study the properties of the space composed by all possible binding cavities. In
      the present contribution, a global mapping of protein cavity space is presented
      by extracting consensus cavities from individual members of protein families and
      clustering them in terms of their shape and exposed physicochemical properties.
      Discovered similarities indicate common binding epitopes in binding pockets
      independent of any possibly given similarity in sequence and fold space.
      Unexpected links between remote targets indicate possible cross-reactivity of
      ligands and suggest putative side effects. The global clustering of cavity space
      is compared to a similar clustering of sequence and fold space and compared to
      chemical ligand space spanned by the chemical properties of small molecules found
      in binding pockets of crystalline complexes. The overall similarity architecture
      of sequence, fold, and cavity space differs significantly. Similarities in cavity
      space can be mapped best to similarities in ligand binding space indicating
      possible cross-reactivities. Most cross-reactivities affect co-factor and other
      endogenous ligand binding sites.

PMID- 19173308
TI  - An unusually small dimer interface is observed in all available crystal
      structures of cytosolic sulfotransferases.
AB  - Cytosolic sulfotransferases catalyze the sulfonation of hormones, metabolites,
      and xenobiotics. Many of these proteins have been shown to form homodimers and
      heterodimers. An unusually small dimer interface was previously identified by
      Petrotchenko et al. (FEBS Lett 2001;490:39-43) by cross-linking, protease
      digestion, and mass spectrometry and verified by site-directed mutagenesis.
      Analysis of the crystal packing interfaces in all 28 available crystal structures
      consisting of 17 crystal forms shows that this interface occurs in all of them.
      With a small number of exceptions, the publicly available databases of biological
      assemblies contain either monomers or incorrect dimers. Even crystal structures
      of mouse SULT1E1, which is a monomer in solution, contain the common dimeric
      interface, although distorted and missing two important salt bridges.

PMID- 19173309
TI  - Accurate domain identification with structure-anchored hidden Markov models,
      saHMMs.
AB  - The ever increasing speed of DNA sequencing widens the discrepancy between the
      number of known gene products, and the knowledge of their function and structure.
      Proper annotation of protein sequences is therefore crucial if the missing
      information is to be deduced from sequence-based similarity comparisons. These
      comparisons become exceedingly difficult as the pairwise identities drop to very
      low values. To improve the accuracy of domain identification, we exploit the fact
      that the three-dimensional structures of domains are much more conserved than
      their sequences. Based on structure-anchored multiple sequence alignments of low
      identity homologues we constructed 850 structure-anchored hidden Markov models
      (saHMMs), each representing one domain family. Since the saHMMs are highly family
      specific, they can be used to assign a domain to its correct family and clearly
      distinguish it from domains belonging to other families, even within the same
      superfamily. This task is not trivial and becomes particularly difficult if the
      unknown domain is distantly related to the rest of the domain sequences within
      the family. In a search with full length protein sequences, harbouring at least
      one domain as defined by the structural classification of proteins database
      (SCOP), version 1.71, versus the saHMM database based on SCOP version 1.69, we
      achieve an accuracy of 99.0%. All of the few hits outside the family fall within
      the correct superfamily. Compared to Pfam_ls HMMs, the saHMMs obtain about 11%
      higher coverage. A comparison with BLAST and PSI-BLAST demonstrates that the
      saHMMs have consistently fewer errors per query at a given coverage. Within our
      recommended E-value range, the same is true for a comparison with SUPERFAMILY.
      Furthermore, we are able to annotate 232 proteins with 530 nonoverlapping domains
      belonging to 102 different domain families among human proteins labelled
      "unknown" in the NCBI protein database. Our results demonstrate that the saHMM
      database represents a versatile and reliable tool for identification of domains
      in protein sequences. With the aid of saHMMs, homology on the family level can be
      assigned, even for distantly related sequences. Due to the construction of the
      saHMMs, the hits they provide are always associated with high quality crystal
      structures. The saHMM database can be accessed via the FISH server at
      http://babel.ucmp.umu.se/fish/.

PMID- 19173310
TI  - Prediction of 3D metal binding sites from translated gene sequences based on
      remote-homology templates.
AB  - Database-scale analysis was performed to determine whether structural models,
      based on remote homologues, are effective in predicting 3D transition metal
      binding sites in proteins directly from translated gene sequences. The extent by
      which side chain modeling alone reduces sensitivity and selectivity is shown to
      be <10%. Surprisingly, selectivity was not dependent on the level of sequence
      homology between template and target, or on the presence of a metal ion in the
      structural template. Applying a modification of the CHED algorithm (Babor et al.,
      Proteins 2008;70:208-217) and machine learning filters, a selectivity of
      approximately 90% was achieved for protein sequences using unrelated structural
      templates over a sequence identity range of 18-100%. Below approximately 18%
      identity, the number of analyzable target-template pairs and predictability of
      metal binding sites falls off sharply. A full third of structural templates were
      found to have target partners only in the remote homology range of 18-30%. In
      this range, nonmetal-binding templates are calculated to be the majority and
      serve to predict with 50% sensitivity at the geometric level. Overall,
      sensitivity at the geometric level for targets having templates in the 18-30%
      sequence identity range is 73%, with an average of one false positive site per
      true site. Protein sequences described as "unknown" in the UniProt database and
      composed largely of unidentified genome project sequences were studied and metal
      binding sites predicted. A web server for prediction of metal binding sites from
      protein sequence is provided.

PMID- 19173311
TI  - Conserved structural and dynamics features in the denatured states of drosophila
      SUMO, human SUMO and ubiquitin proteins: Implications to sequence-folding
      paradigm.
AB  - We have characterized here the structural and dynamics properties of urea
      denatured state of dSmt3 by multidimensional NMR at 27 degrees C and pH 5.6. The
      various results suggest that hydrophobic clusters as well as different native and
      non-native secondary structural elements are transiently formed. The backbone in
      the regions Gln26-Lys31 and Gly47-Gln60 shows conformationally restricted
      motions. The AABUF profile of the sequence reflected that this region has the
      highest tendency to undergo hydrophobic clustering and may thus assist the
      formation of transient structures. The secondary chemical shifts and coupling
      constants indicated that this region has strong tendency to occupy the broad beta
      domain of (phi,psi) space. A number of NMR parameters indicated that the region
      Asp58-Gln60 (corresponding to beta3-beta4 turn in the folded state) has residual
      turn-like structure. The present structural and dynamics results on urea
      denatured dSmt3 have been compared with the previously published results on
      denatured states of similar fold proteins e.g. human SUMO-1 (55% homologous),
      ubiquitin (13.8% homologous) and GB1. Although the sequence homology is rather
      poor between them, the residual structure in all cases seems to be largely native
      type. The implications of these to sequence-folding paradigm and initial folding
      processes have been discussed.

PMID- 19173312
TI  - Structural and dynamic effects of cholesterol at preferred sites of interaction
      with rhodopsin identified from microsecond length molecular dynamics simulations.
AB  - An unresolved question about GPCR function is the role of membrane components in
      receptor stability and activation. In particular, cholesterol is known to affect
      the function of membrane proteins, but the details of its effect on GPCRs are
      still elusive. Here, we describe how cholesterol modulates the behavior of the
      TM1-TM2-TM7-helix 8(H8) functional network that comprises the highly conserved
      NPxxY(x)(5,6)F motif, through specific interactions with the receptor. The
      inferences are based on the analysis of microsecond length molecular dynamics
      (MD) simulations of rhodopsin in an explicit membrane environment. Three regions
      on the rhodopsin exhibit the highest cholesterol density throughout the
      trajectory: the extracellular end of TM7, a location resembling the high-density
      sterol area from the electron microscopy data; the intracellular parts of TM1,
      TM2, and TM4, a region suggested as the cholesterol binding site in the recent X
      ray crystallography data on beta(2)-adrenergic GPCR; and the intracellular ends
      of TM2-TM3, a location that was categorized as the high cholesterol density area
      in multiple independent 100 ns MD simulations of the same system. We found that
      cholesterol primarily affects specific local perturbations of the helical TM
      domains such as the kinks in TM1, TM2, and TM7. These local distortions, in turn,
      relate to rigid-body motions of the TMs in the TM1-TM2-TM7-H8 bundle. The
      specificity of the effects stems from the nonuniform distribution of cholesterol
      around the protein. Through correlation analysis we connect local effects of
      cholesterol on structural perturbations with a regulatory role of cholesterol in
      the structural rearrangements involved in GPCR function.

PMID- 19173313
TI  - Characterization of a diagnostic Fab fragment binding trimeric Lewis X.
AB  - Lewis X trisaccharides normally function as essential cell-cell interaction
      mediators. However, oligomers of Lewis X trisaccharides expressed by the parasite
      Schistosoma mansoni seem to be related to its evasion of the immune response of
      its human host. Here we show that monoclonal antibody 54-5C10-A, which is used to
      diagnose schistosomiasis in humans, interacts with oligomers of at least three
      Lewis X trisaccharides, but not with monomeric Lewis X. We describe the sequence
      and the 2.5 A crystal structure of its Fab fragment and infer a possible mode of
      binding of the polymeric Lewis X from docking studies. Our studies indicate a
      radically different mode of binding compared to Fab 291-2G3-A, which is specific
      for monomeric Lewis X, thus providing a structural explanation of the diagnostic
      success of 54-5C10-A.

PMID- 19173314
TI  - X-ray crystal structure of a CRISPR-associated RAMP module [corrected] Cmr5
      protein [corrected] from Thermus thermophilus HB8.

PMID- 19173315
TI  - Folding simulations of Trp-cage mini protein in explicit solvent using biasing
      potential replica-exchange molecular dynamics simulations.
AB  - Replica exchange molecular dynamics (RexMD) simulations are frequently used for
      studying structure formation and dynamics of peptides and proteins. A significant
      drawback of standard temperature RexMD is, however, the rapid increase of the
      replica number with increasing system size to cover a desired temperature range.
      A recently developed Hamiltonian RexMD method has been used to study folding of
      the Trp-cage protein. It employs a biasing potential that lowers the backbone
      dihedral barriers and promotes peptide backbone transitions along the replica
      coordinate. In two independent applications of the biasing potential RexMD method
      including explicit solvent and starting from a completely unfolded structure the
      formation of near-native conformations was observed after 30-40 ns simulation
      time. The conformation representing the most populated cluster at the final
      simulation stage had a backbone root mean square deviation of approximately 1.3 A
      from the experimental structure. This was achieved with a very modest number of
      five replicas making it well suited for peptide and protein folding and
      refinement studies including explicit solvent. In contrast, during five
      independent continuous 70 ns molecular dynamics simulations formation of
      collapsed states but no near native structure formation was observed. The
      simulations predict a largely collapsed state with a significant helical
      propensity for the helical domain of the Trp-cage protein already in the unfolded
      state. Hydrogen bonded bridging water molecules were identified that could play
      an active role by stabilizing the arrangement of the helical domain with respect
      to the rest of the chain already in intermediate states of the protein.

PMID- 19173317
TI  - Specific labeling of peptidoglycan precursors as a tool for bacterial cell wall
      studies.
AB  - Because of its importance for bacterial cell survival, the bacterial cell wall is
      an attractive target for new antibiotics in a time of great demand for new
      antibiotic compounds. Therefore, more knowledge about the diverse processes
      related to bacterial cell wall synthesis is needed. The cell wall is located on
      the exterior of the cell and consists mainly of peptidoglycan, a large
      macromolecule built up from a three-dimensional network of aminosugar strands
      interlinked with peptide bridges. The subunits of peptidoglycan are synthesized
      inside the cell before they are transported to the exterior in order to be
      incorporated into the growing peptidoglycan. The high flexibility of the cell
      wall synthesis machinery towards unnatural derivatives of these subunits enables
      research on the bacterial cell wall using labeled compounds. This review
      highlights the high potential of labeled cell wall precursors in various areas of
      cell wall research. Labeled precursors can be used in investigating direct cell
      wall-antibiotic interactions and in cell wall synthesis and localization studies.
      Moreover, these compounds can provide a powerful tool in the elucidation of the
      cell wall proteome, the "wallosome," and thus, might provide new targets for
      antibiotics.

PMID- 19173322
TI  - Determination of anti-malaria agent chloroquine using single drop liquid-liquid
      liquid microextraction.
AB  - A simple, sensitive, and inexpensive single drop liquid-liquid-liquid
      microextraction combined with isocratic RP-HPLC and UV detection was developed
      for the determination of anti-malaria drug, chloroquine. The target compound was
      extracted from alkaline aqueous sample solution (adjusted to 0.5 mol/L sodium
      hydroxide) through a thin layer of organic solvent membrane and back-extracted to
      an acidic acceptor drop (adjusted to 0.02 mol/L phosphoric acid) suspended on the
      tip of a 25 microL HPLC syringe in the organic layer. This syringe was also used
      for direct injection after extraction. The linear range was 1-200 microg/L. The
      LOD and LOQ were 0.3 and 1.0 microg/L, respectively. Intra-and inter-day
      precisions were less than 2.0 and 2.3%, respectively. The real samples were
      successfully analyzed using the proposed method. The recoveries of spiked samples
      were more than 94.6%.

PMID- 19173323
TI  - Analysis of polycyclic aromatic hydrocarbons in atmospheric particulate samples
      by microwave-assisted extraction and liquid chromatography.
AB  - A methodology based on microwave-assisted extraction (MAE) and LC with
      fluorescence detection (FLD) was investigated for the efficient determination of
      15 polycyclic aromatic hydrocarbons (PAHs) regarded as priority pollutants by the
      US Environmental Protection Agency and dibenzo(a,l)pyrene in atmospheric
      particulate samples. PAHs were successfully extracted from real outdoor
      particulate matter (PM) samples with recoveries ranging from 81.4 +/- 8.8 to
      112.0 +/- 1.1%, for all the compounds except for naphthalene (62.3 +/- 18.0%) and
      anthracene (67.3 +/- 5.7%), under the optimum MAE conditions (30.0 mL of ACN for
      20 min at 110 degrees C). No clean-up steps were necessary prior to LC analysis.
      LOQs ranging from 0.0054 ng/m(3 )for benzo(a)anthracene to 0.089 ng/m(3) for
      naphthalene were reached. The validated MAE methodology was applied to the
      determination of PAHs from a set of real world PM samples collected in Oporto
      (north of Portugal). The sum of particulate-bound PAHs in outdoor PM ranged from
      2.5 and 28 ng/m(3).

PMID- 19173316
TI  - Crystal structure of a novel Sm-like protein of putative cyanophage origin at
      2.60 A resolution.
AB  - ECX21941 represents a very large family (over 600 members) of novel, ocean
      metagenome-specific proteins identified by clustering of the dataset from the
      Global Ocean Sampling expedition. The crystal structure of ECX21941 reveals
      unexpected similarity to Sm/LSm proteins, which are important RNA-binding
      proteins, despite no detectable sequence similarity. The ECX21941 protein
      assembles as a homopentamer in solution and in the crystal structure when
      expressed in Escherichia coli and represents the first pentameric structure for
      this Sm/LSm family of proteins, although the actual oligomeric form in vivo is
      currently not known. The genomic neighborhood analysis of ECX21941 and its
      homologs combined with sequence similarity searches suggest a cyanophage origin
      for this protein. The specific functions of members of this family are unknown,
      but our structure analysis of ECX21941 indicates nucleic acid-binding
      capabilities and suggests a role in RNA and/or DNA processing.

PMID- 19173324
TI  - Statistical mixture design investigation of fractionated and total extracts from
      Erythrina speciosa Andrews leaves.
AB  - The simplex centroid mixture design for the ethanol, dichloromethane, hexane and
      acetone solvents has been applied to the extraction of crude mass and the fiber,
      organic, neutral and basic fractions as well as the fractionation residues of
      Erythrina speciosa Andrews leaves. Binary and ternary synergic solvent
      interactions are seen to provide dominant contributions to the extraction of both
      crude mass and all the fractions. Quadratic and special cubic mixture models
      precisely predict the extracted quantities of each fraction and the residue as a
      function of the proportions of the four solvents. Different solvent mixtures are
      found to be the most efficient extractors for the different fractions: binary
      dichloromethane-hexane mixtures for the fiber fraction, ternary ethanol
      dichloromethane-acetone mixtures for the neutral fraction, binary ethanol
      dichloromethane mixtures for the organic fraction, crude extract and residue
      values and ternary ethanol-dichloromethane-hexane mixtures for the basic
      fraction. Principal component analysis shows that the ethanol-dichloromethane
      mixtures are important for extracting large quantities of the basic and organic
      fractions as well as of the residue and crude masses.

PMID- 19173325
TI  - Application of HPLC-NMR for the rapid chemical profiling of a Southern Australian
      sponge, Dactylospongia sp.
AB  - Rapid chemical profiling of the antitumour active crude dichloromethane extract
      of the marine sponge, Dactylospongia sp. was undertaken. A combination of both
      offline (HPLC followed by NMR and MS) and on-line (on-flow and stop-flow HPLC
      NMR) chemical profiling approaches was adopted to establish the exact nature of
      the major constituents present in the dichloromethane extract of this sponge. On
      flow HPLC-NMR analysis was employed to initially identify components present in
      the dichloromethane extract, while stop-flow HPLC-NMR experiments were then
      conducted on the major component present, resulting in the partial identification
      of pentaprenylated p-quinol (5). Subsequent off-line RP semi-preparative HPLC
      isolation of 5 followed by detailed spectroscopic analysis using NMR and MS
      permitted the complete structure to be established. This included the first
      complete carbon NMR chemical shift assignment of 5 based on the heteronuclear 2-D
      NMR experiments, together with the first report of its antitumour activity. This
      study represents one of the few reports describing the application of HPLC-NMR to
      chemically profile secondary metabolites from a marine organism.

PMID- 19173328
TI  - QM/MM methods for biomolecular systems.
AB  - Combined quantum-mechanics/molecular-mechanics (QM/MM) approaches have become the
      method of choice for modeling reactions in biomolecular systems. Quantum
      mechanical (QM) methods are required for describing chemical reactions and other
      electronic processes, such as charge transfer or electronic excitation. However,
      QM methods are restricted to systems of up to a few hundred atoms. However, the
      size and conformational complexity of biopolymers calls for methods capable of
      treating up to several 100,000 atoms and allowing for simulations over time
      scales of tens of nanoseconds. This is achieved by highly efficient, force-field
      based molecular mechanics (MM) methods. Thus to model large biomolecules the
      logical approach is to combine the two techniques and to use a QM method for the
      chemically active region (e.g., substrates and co-factors in an enzymatic
      reaction) and an MM treatment for the surroundings (e.g., protein and solvent).
      The resulting schemes are commonly referred to as combined or hybrid QM/MM
      methods. They enable the modeling of reactive biomolecular systems at a
      reasonable computational effort while providing the necessary accuracy.

PMID- 19173333
TI  - Improved protein separation by microchip isoelectric focusing with stepwise
      gradient of electric field strength.
AB  - A stepwise gradient of electric field strength was proposed for microchip IEF
      based protein separation, by which after focusing at low voltages, IEF was
      performed by applying higher separation voltages step-by-step. A linear
      relationship between the focusing time and the inverse of the electric field
      strength was found. In addition, the conductivity of an established pH gradient
      showed a negative but nonlinear correlation with the applied voltage. Based on
      the above-mentioned results, a stepwise gradient of electric field strength,
      ranging from 160 to 1500 V/cm was applied in the separation of proteins extracted
      from Escherichia coli in a straight glass microchip channel permanently coated by
      polyacrylamide. Compared to the conventional separation performed under a
      constant field strength of 750 V/cm, the increased stepwise gradient of electric
      field strength resulted in improved resolution and decreased focusing time, while
      without the negative effects of Joule heat for protein separation. All these
      results demonstrated that such a method might be of great significance to achieve
      high resolution and high-throughput analysis of complex protein samples for
      microchip IEF.

PMID- 19173337
TI  - Synthesis and in-vitro cytotoxicity evaluation of novel naphtindolizinedione
      derivatives, part II: improved activity for aza-analogues.
AB  - Our previous investigation on potential antitumor agents now got enriched by the
      evaluation of in-vitro activity against a full panel of NCI cancer cell lines for
      five new compounds. The concurrent presence in the molecular structure of a
      nitrogen atom in the aromatic system and a N,N-dimethylaminoethyl amide chain
      play a decisive role to enhance cytotoxicity. The N,N-anti compound 14 shows a
      higher activity than its N,N-syn isomer, exhibiting the best selective inhibition
      against the melanoma MALME-3M cell line, with a GI(50)-value (= 30 nM)
      corresponding to a 330-fold increase in activity compared to the corresponding
      deaza-analogue. Compound 14 is efficiently synthesized by aminolysis of the ester
      obtained as a single regio-isomer by an one-pot three-component procedure
      involving metal-assisted cyclization under microwave irradiation conditions.

PMID- 19173336
TI  - Synthesis and biological evaluation of distamycin analogues - new potential
      anticancer agents.
AB  - Eight of analogues of distamycin, potential minor-groove binders, were
      synthesized and tested for in-vitro cytotoxicity towards human breast cancer
      cells MCF-7 and MDA-MB-231. The method of synthesis is simple and convenient. All
      of the compounds 1-8 showed antiproliferative and cytotoxic effects against both
      cell lines in the range 3.47 to 12.53 microM for MDA-MB-231 and 4.35 to 12.66
      microM for MCF-7. All compounds demonstrated activity against DNA topoisomerases
      I and II at a concentration of 50 microM. The ethidium bromide assay showed that
      these compounds bind to plasmid pBR322, yet weaker than distamycin. Further
      investigations concerning the mechanism of cytotoxicity are now in progress, but
      the IC(50) values suggest that synthetic distamycin analogues with a free amino
      group, 3-4 and 7-8, can serve as potential carriers of strong acting elements, e.
      g. alkylating groups.

PMID- 19173332
TI  - The functional neuroanatomy of geriatric depression.
AB  - OBJECTIVE: Positron Emission Tomography (PET) studies of cerebral glucose
      metabolism have demonstrated sensitivity in evaluating the functional
      neuroanatomy of treatment response variability in depression, as well as in the
      early detection of functional changes associated with incipient cognitive
      decline. The evaluation of cerebral glucose metabolism in late life depression
      may have implications for understanding treatment response variability, as well
      as evaluating the neurobiological basis of depression in late life as a risk
      factor for dementia. METHODS: Sixteen patients with geriatric depression and 13
      comparison subjects underwent resting PET studies of cerebral glucose metabolism,
      as well as magnetic resonance (MR) imaging scans to evaluate brain structure.
      RESULTS: Cerebral glucose metabolism was elevated in geriatric depressed patients
      relative to comparison subjects in anterior (right and left superior frontal
      gyrus) and posterior (precuneus, inferior parietal lobule) cortical regions.
      Cerebral atrophy (increased cerebrospinal fluid [CSF] and decreased grey and
      white matter volumes) were observed in some of these regions, as well. Regional
      cerebral metabolism was positively correlated with severity of depression and
      anxiety symptoms. CONCLUSIONS: In contrast to decreased metabolism observed in
      normal aging and neurodegenerative conditions such as Alzheimer's disease,
      cortical glucose metabolism was increased in geriatric depressed patients
      relative to demographically matched controls, particularly in brain regions in
      which cerebral atrophy was observed, which may represent a compensatory response.

PMID- 19173338
TI  - Nitric oxide synthase inhibition by pentacycloundecane conjugates of
      aminoguanidine and tryptamine.
AB  - This paper describes the synthesis and in-vitro activity of pentacycloundecane
      conjugated aminoguanidine and tryptamine analogues on nitric oxide synthase (NOS)
      using rat brain homogenate. Both aminoguanidine and tryptamine-derived NOS
      inhibitors show selectivity towards the inducible and neuronal isoforms of the
      NOS enzyme, but are weak inhibitors and complete inhibition of the enzyme occurs
      only at high millimolar concentrations. In view of the increased NOS inactivation
      observed with alkyl substitution of these structures, the present study aimed to
      evaluate the effect of the pentacycloundecane cage moiety as an alkyl substituent
      on the in vitro NOS inhibition of aminoguanidine and tryptamine compounds.
      Comparison of the IC(50) values of aminoguanidine (IC(50) = 2.306x10(-3) M) and 8
      imino-N-guanidino-pentacyclo-undecane 2 (IC(50) = 8.803x10(-5) M) revealed a more
      than 26-fold increase in potency. The ability of tryptamine to inhibit NOS
      activity was also markedly improved by the various pentacycloundecane
      substituents. The compounds, 3-hydroxy-4-[3-(2-aminoethyl)indole]
      azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecane 4 and 8-[3-(2
      aminoethyl) indole]-pentacyclo[5.4.0(2,6).0(3,10).0(5,9)]undecane 7 showed the
      best activity of the tryptamine analogues with a more than 3-fold increase in
      nitric oxide synthase inhibition. The results confirmed that the
      pentacycloundecane structure substantially enhanced the NOS inhibitory potency as
      observed for the six new NOS inhibitors.

PMID- 19173339
TI  - Special issue: microscale separations.

PMID- 19173340
TI  - Microseparation of membrane proteins.
AB  - Membrane proteins are generally of natural low abundance and insoluble to aqueous
      solutions. Thus, investigation of membrane proteins is relatively hampered since
      efficient separation of membrane proteins are rather challenging. Microseparation
      approaches certainly play an essential role in fulfilling such demanding
      investigations due to their significant advantages of high throughput, reduced
      separation time, and low sample consumption. In this review, recent developments
      of microseparation are documented with aspects of three key separation methods,
      including CE, micro-LC and microchip. Preparation of membrane proteins prior to
      separation is also discussed, including solubilization and preconcentration.
      Certainly, more applications of microseparation approaches in membrane protein
      separations can be expected in the near future.

PMID- 19173341
TI  - Metal ion analysis using microchip CE with chemiluminescence detection based on
      1,10-phenanthroline-hydrogen peroxide reaction.
AB  - We developed a microchip CE method with chemiluminescence (CL) detection using
      the reaction of 1,10-phenanthroline and hydrogen peroxide for separation and
      determination of metal ions, where the metal ions acted as catalysts for the CL
      reaction. The microchip consisted of two microchannels that crossed at the
      intersection and four reservoirs that accessed the ends of the channels. The
      metal ions in the sample solution migrated in the channel along with 1,10
      phenanthroline included in a running solution, and then mixed with hydrogen
      peroxide in one of the reservoirs to emit CL. The light was detected with a
      photomultiplier tube located just above the reservoir. Two metal ion groups, the
      platinum metal group (Ru(III), Rh(III), Pd(II), Os(VIII), Ir(III), and Pt(IV))
      and the fourth periodic transition metal group (Cu(II), Fe(II), Co(II), and
      Ni(II)) were examined using the present system. The lowest detection limit was
      observed for Os(VIII); Os(VIII) responded over the range of 7.5x10(-12)-1.0x10(-8
      )M with the detection limit of 7.5x10(-12 )M (about 38 zmol) (S/N = 3). The mixed
      solution of Ru(III), Rh(III), Pd(II), Os(VIII), Ir(III), and Pt(IV) could be
      analyzed using this system within about 2.5 min. In addition, the system was
      applied to the determination of Cu(II) concentration in a city water supply.

PMID- 19173342
TI  - Pharmacovigilance in pregnancy using population-based linked datasets.
AB  - PURPOSE: National dispensing data for subsidized prescription medicines have
      recently been approved for linkage to the population-based health datasets in
      Western Australia (WA), creating the capacity to study how these medicines are
      used and their impact on pregnancy outcomes. METHODS: Pregnancy events were
      identified in the Hospital Morbidity Data System from 2002 to 2005 (N = 164,278
      admissions; N = 98,265 women) and linked to the midwives' notification system
      (MNS), the registry of births and deaths, the Western Australian birth defects
      registry and the pharmaceutical benefit scheme. Dispensing records were extracted
      for each pregnancy event (N = 1,276,084 dispenses). RESULTS: There were 106,074
      births, 1527 ectopic pregnancies and 25,180 terminations of pregnancy. Dispensed
      medicines were linked to 28.0% of the pregnancy events. Multiple birth
      pregnancies were 50% more likely to be dispensed a medicine in the first
      trimester. As parity increased, so did the likelihood of a medicine being
      dispensed in pregnancy. Women who were dispensed a medicine were twice as likely
      to smoke during pregnancy and were 14% more likely to have a registered birth
      defect. During the first trimester, medicines from category D or X of the risk of
      drug use in pregnancy were dispensed to 2.1% of all pregnancy events. The WHO ATC
      'Psychoanaleptics' category was dispensed to 3.8% of all pregnancy events.
      CONCLUSION: Linkage of dispensing data to pregnancy events is feasible and this
      approach to post-marketing surveillance will add to the resources available in
      Australia to investigate pregnancy outcomes in relation to the safe use of
      prescribed medicines in pregnancy.

PMID- 19173344
TI  - Arrays, lasers, balloons and first trimester sonographic screening: an
      introduction to the 2008 International Society for Prenatal Diagnosis meeting
      issue.

PMID- 19173343
TI  - Conformational study of poly-DeltaAbu peptides and construction of amphipathic
      nanostructure.
AB  - Generally, it is believed that alpha,beta-dehydroamino acid residues are most
      stable in the Z- form rather than in the E- form. In this study, it has been
      shown that poly-DeltaAbu exists in alternate Delta(E)Abu and Delta(Z)Abu form,
      with phi, psi values of approximately 0 degrees , 80 degrees and 35 degrees , 27
      degrees for the E- and Z- forms, respectively, rather than the all Z- form. The
      conformational results for the peptides Ac-DeltaAbu(2)-NHMe and Ac-L/D-Ile
      Delta(Z)Abu/Delta(E)Abu-NHMe suggest the incorporation of DeltaAbu in both the Z-
      and E- forms, which is consistent with the available observations in natural
      systems. Because of adoption of phi, psi values corresponding to the collagen
      type structure ( approximately -30 degrees , 120 degrees ) by Ile residue and
      with phi, psi values in the left-handed helical region for Delta(Z)Abu residue,
      the peptide Ac-(L-Ile-Delta(Z)Abu)(3)-NHMe adopts an amphipathic left-handed
      helical beta-sheet type structure. This structure is stabilized by network of
      hydrogen bonding, carbonyl-carbonyl, and CH-O interactions and can be exploited
      for the construction of antimicrobial peptides and nanomaterials.

PMID- 19173345
TI  - Rapid prenatal diagnosis of common chromosome aneuploidies by QF-PCR, results of
      9 years of clinical experience.
AB  - BACKGROUND: Despite being deliberately targeted to common chromosome
      aneuploidies, the rapid quantitative fluorescent polymerase chain reaction (QF
      PCR) tests can detect the majority of chromosome abnormalities in prenatal
      diagnosis. The main advantages of this assay are low cost, speed and automation
      allowing large-scale application. METHODS: We developed a QF-PCR test that was
      applied on 43 000 clinical samples reporting results in 24 h. Most common
      indications were biochemical risk (32%) and advanced maternal age (30%). Samples
      were also tested by cytogenetic analysis and the results compared. RESULTS:
      Aneuploidies involving chromosomes 21, 18, 13, X and Y were detected with 100%
      specificity. Several cases of partial trisomies and mosaicism were also
      identified. Overall 95% of clinically relevant abnormalities were readily
      detected and termination of affected pregnancies could be performed without
      waiting for the cytogenetic results. CONCLUSIONS: Our study supports the
      possibility of reducing the load of prenatal cytogenetic tests if the pregnancies
      are carefully monitored by non-invasive screening. In case of abnormal QF-PCR
      results, medical action can be taken within few hours from sampling. In cases of
      negative QF-PCR results, cytogenetic analyses might only be performed for fetuses
      with ultrasound abnormalities. In countries where large-scale cytogenetic tests
      are not available, QF-PCR may be used as the only prenatal diagnostic procedure.

PMID- 19173346
TI  - Early first-trimester free beta-hCG and PAPP-A serum distributions in
      monochorionic and dichorionic twins.
AB  - BACKGROUND: In the Netherlands, prenatal screening for trisomy 21 in the first
      trimester of pregnancy for singletons is conducted through a combined test based
      on maternal age, nuchal translucency measurement and maternal serum free beta-hCG
      and PAPP-A. In our clinic risk calculations in twins are currently based on the
      NT of both fetuses instead of the combined test. In this study we looked at
      differences in early first-trimester free beta-hCG and PAPP-A between mono- and
      dichorionic twins. METHODS: A total of 202 twin pregnant women participated in
      the study and agreed to donate first-trimester serum for research. RESULTS: The
      data of 200 twins with normal outcome were used for setting up reference values
      for free beta-hCG and PAPP-A. Trisomy 21 was identified in the two remaining
      pregnancies. The overall median weight-corrected MoM was 1.99 for free beta-hCG,
      and 2.14 for PAPP-A in all twins. Monochorionic twins have a significantly lower
      free beta-hCG weight-corrected MoM (1.53 vs 2.11; Mann-Whitney U, p=0.002) and a
      significantly lower PAPP-A weight-corrected MoM (1.59 vs 2.40; Mann-Whitney U,
      p=0.003) compared to dichorionic. CONCLUSION: This study strengthened the need to
      make a distinction between mono- and dichorionic twins for the risk calculation
      in Down syndrome screening as biochemical markers are significantly lower in
      monochorionic than in dichorionic twins.

PMID- 19173347
TI  - Current controversies in prenatal diagnosis 1: Is aneuploidy testing by PGD
      indicated for all infertile patients undergoing IVF?

PMID- 19173348
TI  - In situ X-ray measurements to probe a new solid-state polycondensation mechanism
      for the design of supramolecular organo-bridged silsesquioxanes.
AB  - A long-range ordered organic/inorganic material is synthesized from a bis-silane,
      (EtO)(3)Si-(CH(2))(3)-NHCONH-C(6)H(4)-NHCONH-(CH(2))(3)-Si(OEt)(3). This
      crosslinked sol-gel solid exhibits a supramolecular organization via
      intermolecular hydrogen bonding interactions between urea groups (-NHCONH-) and
      covalent siloxane bonding, triple bond Si-O-Si triple bond. Time-resolved in situ
      X-ray measurements (coupling small- and wide-angle X-ray scattering techniques)
      are performed to follow the different steps involved in the synthetic process. A
      new mechanism based on the crystallization of the hydrolyzed species followed by
      their polycondensation in solid state is proposed.

PMID- 19173349
TI  - (1)H and (13)C NMR data of methyl tetra-O-benzoyl-D-pyranosides in acetone-d(6).
AB  - Complete assignments of (1)H- and (13)C-NMR resonances of five methyl tetra-O
      benzoyl-D-pyranosides based on (1)H, (13)C, 2D DQF-COSY, HMQC, HMBC and HSQC
      TOCSY experiments have been performed.

PMID- 19173350
TI  - Identification of degradation products in stressed tablets of Rabeprazole sodium
      by HPLC-hyphenated techniques.
AB  - Three unknown impurities of Rabeprazole, a proton pump inhibitor, were formed in
      the formulated drug under the stress conditions, [40 degrees C/75% relative
      humidity (RH) for 6 months] with relative retention times (RRTs) 0.17, 0.22 and
      0.28. The Impurity-I (0.17 RRT) was isolated using preparative HPLC and
      characterized by NMR and MS. The other two impurities, Impurity-II (RRT 0.22) and
      Impurity-III (RRT 0.28) could not be isolated, hence they are characterized by
      HPLC-hyphenated techniques, LC-NMR and high-resolution LC-MS. On the basis of the
      spectral data, the Impurity-I, Impurity-II and Impurity-III were characterized as
      1-(1H-benzo[d]imidazol-2-yl)-3-methyl-4-oxo-1,4-dihydropyridine-2-carboxylic
      acid, 1H-benzo [d] imidazole-2-sulfonic acid and 4-(3-methoxy propoxy)-3-methyl-2
      pyridine carboxylic acid, respectively.

PMID- 19173351
TI  - Peptide-functionalized, low-biofouling click multilayers for promoting cell
      adhesion and growth.

PMID- 19173352
TI  - Catalytic, enantioselective ring opening of aziridines.
AB  - Cooperative metal centers in a bimetallic catalyst facilitate the highly
      enantioselective ring opening of meso aziridines 1 with silyl nucleophiles (see
      scheme; TMS = trimethylsilyl). The 1,2-azidoamides 2 and 1,2-amidonitriles 3
      obtained in this way in high yields and with up to 99% ee are valuable precursors
      to enantiomerically pure 1,2-diamines and beta-amino acids.

PMID- 19173353
TI  - Highly proton-conducting self-humidifying microchannels generated by copolymer
      brushes on a scaffold.
AB  - Filling in the gaps: Macroporous silicon membranes modified with sulfonated
      polymer brushes have been synthesized by pore-filling surface polymerization (see
      picture) to give proton-conducting channels with tailor-made, finely tuned
      physicochemical characteristics. These membranes display high conductivity values
      (ca. 10(-2) S cm(-1)) regardless of the humidity, thus surpassing the performance
      of nafion.

PMID- 19173354
TI  - A designer axially chiral amino sulfonamide as an efficient organocatalyst for
      direct asymmetric mannich reactions of N-Boc-protected imines.
AB  - The moderate nucleophilicity of the axially chiral amino sulfonamide (S)-1
      suppresses the problematic side reactions, including aldol reactions, in the
      asymmetric Mannich reaction of N-Boc-protected imines with aldehydes. The
      corresponding adducts are obtained in good yield and excellent stereoselectivity
      (see scheme; Boc = tert-butoxycarbonyl, Tf = trifluoromethanesulfonyl).

PMID- 19173355
TI  - Responsive supramolecular gels constructed by crown ether based molecular
      recognition.
AB  - Responsive supramolecular gels were constructed from crown ether terminated four
      arm star poly(epsilon-caprolactone) (PCL-DB24C8) and dibenzylammonium-terminated
      two-arm PCL-DBAS (see scheme), exploiting the formation of pseudorotaxane
      linkages between crown ether and ammonium moieties. The resultant supramolecular
      gels exhibit thermo- and pH-induced reversible gel-sol transition.

PMID- 19173356
TI  - Patterned monolayers of neutral and charged functionalized manganese arene
      complexes on a highly ordered pyrolytic graphite surface.
AB  - Complex patterns: The arene manganese tricarbonyl complexes [Mn(eta(5)-2,5
      didodecoxy-1,4-semiquinone)(CO)(3)] and [Mn(eta(6)-1,4-dioctyloxybenzene)(CO)(3)]
      BF(4) form patterned monolayers on the surface of highly ordered pyrolytic
      graphite (HOPG), as a result of hydrogen-bonding, hydrophobic, and electrostatic
      interactions, leading to an ordered 2D array of manganese atoms or ions.

PMID- 19173357
TI  - Exploiting the divergent reactivity of aryl-palladium intermediates for the rapid
      assembly of fluorene and phenanthrene derivatives.
AB  - They all fall down: The value of domino processes can be greatly enhanced when
      the possibility exists for one to selectively diverge from a common intermediate.
      In preliminary studies the dual reactivity of aryl-palladium intermediates is
      exploited. A diverse array of fluorene and phenanthrene derivatives were
      synthesized in a rapid and efficient manner (see scheme).

PMID- 19173358
TI  - Air-stable {(C5H5)Co} catalysts for [2+2+2] cycloadditions.
AB  - Cobalt cyclopentadienyl complexes incorporating a fumarate and a CO ligand (see
      picture) efficiently catalyze inter- and intramolecular [2+2+2] cycloadditions of
      alkynes, nitriles, and/or alkenes to give benzenes, pyridines, or 1,3
      cyclohexadienes. Unlike catalysts such as [CpCo(CO)(2)] or [CpCo(C(2)H(4))(2)]
      (Cp = C(5)H(5)), they are air-stable, easy to handle, compatible with microwave
      conditions, and do not necessarily require irradiation to be active.

PMID- 19173359
TI  - Fast biosynthesis of GFP molecules: a single-molecule fluorescence study.
AB  - It's not easy being green: Real-time visualization of labeled ribosomes and de
      novo synthesized green fluorescent protein molecules using single-molecule
      sensitive fluorescence microscopy demonstrates that the mutant GFPem is produced
      with a characteristic time of five minutes. Fluorescence of the fastest GFP
      molecules appears within one minute (see picture).

PMID- 19173360
TI  - Nickel-catalyzed cross-coupling of non-activated and functionalized alkyl halides
      with alkyl Grignard reagents.
AB  - Reacting in the 'Ni'ck of time: The title reaction is realized by using an
      isolated Ni(II) complex (1). The catalysis tolerates a wide range of important
      functional groups that are often incompatible with Grignard reagents in cross
      coupling reactions.

PMID- 19173361
TI  - New principles for glycoside-bond formation.
AB  - Increased understanding of the important roles that oligosaccharides and
      glycoconjugates play in biological processes has led to a demand for significant
      amounts of these materials for biological, medicinal, and pharmacological
      studies. Therefore, tremendous effort has been made to develop new procedures for
      the synthesis of glycosides, whereby the main focus is often the formation of the
      glycosidic bonds. Accordingly, quite a few review articles have been published
      over the past few years on glycoside synthesis; however, most are confined to
      either a specific type of glycoside or a specific strategy for glycoside
      synthesis. In this Review, new principles for the formation of glycoside bonds
      are discussed. Developments, mainly in the last ten years, that have led to
      significant advances in oligosaccharide and glycoconjugate synthesis have been
      compiled and are evaluated.

PMID- 19173362
TI  - Anode catalysts for direct ethanol fuel cells utilizing directly solar light
      illumination.
AB  - Shine a light: A PtNiRu/TiO(2) anode catalyst for direct ethanol fuel cells shows
      photocatalytic activity. The peak current density for ethanol oxidation under
      solar light illumination is 2-3 times greater than that in the absence of solar
      light. Ethanol is oxidized by light-generated holes, and the electrons are
      collected by the TiO(2) support to generate the oxidation current.Novel
      PtNiRu/TiO(2) anode catalysts for direct ethanol fuel cells (DEFCs) were prepared
      from PtNiRu nanoparticles (1:1:1 atomic ratios) and a nanoporous TiO(2) film by a
      sol-gel and electrodeposition method. The performances of the catalysts for
      ethanol oxidation were investigated by cyclic voltammetry, chronoamperometry and
      electrochemical impedance spectroscopy. The results indicate a remarkable
      enhancement of activity for ethanol oxidation under solar light illumination.
      Under solar light illumination, the generated oxidation peak current density is
      24.6 mA cm(-2), which is about 2.5 times higher than that observed without solar
      light (9.9 mA cm(-2)). The high catalytic activity of the PtNiRu/TiO(2) complex
      catalyst for the electrooxidation of ethanol may be attributed to the modified
      metal/nanoporous TiO(2) film, and the enhanced electrooxidation of ethanol under
      solar light may be due to the photogeneration of holes in the modified nanoporous
      TiO(2) film.

PMID- 19173363
TI  - Palladium-catalysed direct 3- or 4-arylation of 2,5-disubstituted pyrrole
      derivatives: an economically and environmentally attractive procedure.
AB  - Straight to the point: The direct 3- or 4-arylation of pyrrole derivatives
      through C--H bond activation proceeds in moderate to good yields using Pd(OAc)(2)
      as catalyst. In contrast to classical coupling procedures, the preparation of an
      organometallic derivative is not required and the major by-products are AcOH/KBr
      instead of metallic salts.

PMID- 19173364
TI  - Nanostructured cobalt oxide clusters in mesoporous silica as efficient oxygen
      evolving catalysts.
AB  - Light, inexpensive, effective: Nanostructured Co(3)O(4) clusters (see picture) in
      mesoporous silica are the first example of a nanometer-sized multielectron
      catalyst made of a first-row transition-metal oxide that evolves oxygen from
      water efficiently. The nanorod bundle structure of the catalyst results in a very
      large surface area, an important factor contributing to the high turnover
      frequency.

PMID- 19173365
TI  - Secondary alkyl halides in transition-metal-catalyzed cross-coupling reactions.
AB  - Enormous effort has gone into the development of metal-catalyzed cross-coupling
      reactions with alkyl halides as electrophilic coupling partners. Whereas a wide
      array of primary alkyl halides can now be used effectively in cross-coupling
      reactions, the synthetic potential of secondary alkyl halides is just beginning
      to be revealed. This Minireview summarizes selected examples of the use of
      secondary alkyl halides as electrophiles in cross-coupling reactions. Emphasis is
      placed on the transition metals employed, the mechanistic pathways involved, and
      implications in terms of the stereochemical outcome of reactions.

PMID- 19173366
TI  - Semisynthesis of a homogeneous glycoprotein enzyme: ribonuclease C: part 1.
AB  - Seven in one blow: The efficient formation of mixed disulfides on the thiol-rich
      fusion protein A followed by subsequent intein cleavage gave the fragment B with
      all seven cysteines protected against oxidation. The native chemical ligation of
      B with synthetic glycopeptide thioesters provides glycoproteins.

PMID- 19173367
TI  - Cobalt growth on the tips of CdSe nanorods.
AB  - Best of both worlds: Reduction of an organometallic Co precursor on preformed
      CdSe nanorods yields two distinct semiconducting-magnetic heterostructures (see
      picture). The selective growth of Co on the tips of CdSe first gives nanosphere
      nanorod dimers, which evolve into nanorod-nanorod structures. In the hybrid
      objects the magnetic properties of Co remain intact, while the luminescence
      properties of CdSe are affected but not completely quenched.

PMID- 19173368
TI  - Protein recognition by an ensemble of fluorescent DNA G-quadruplexes.
AB  - Sniffing out proteins: Fluorescent DNA G-quadruplexes have been used for building
      versatile signaling receptors for proteins in a single solution. Introducing a
      protein sample to the ensemble results in a unique emission signature for
      unambiguous identification (see scheme, R = fluorophore). The self-assembled,
      pattern-based protein detection systems are easily fabricated, have the potential
      for high-throughput operations, and have the ability to handle small protein
      samples.

PMID- 19173369
TI  - Drug delivery by an enzyme-mediated cyclization of a lipid prodrug with unique
      bilayer-formation properties.
AB  - Special delivery: Liposomal drug-delivery systems in which prodrugs are activated
      specifically by disease-associated enzymes have great potential for the treatment
      of severe diseases, such as cancer. A new type of phospholipid-based prodrug has
      the ability to form stable small unilamellar vesicles (see picture). Activation
      of the prodrug vesicles by the enzyme sPLA(2) initiates a cyclization reaction,
      which leads to the release of the drug.

PMID- 19173371
TI  - Current considerations in the treatment of generalized anxiety disorder.
AB  - Generalized anxiety disorder (GAD) is a chronic disorder that frequently co
      occurs with a variety of co-morbidities in patients with somatic conditions and
      other mental disorders. GAD is highly prevalent and is one of the most common
      anxiety disorders seen by primary care physicians. The individual and societal
      cost associated with GAD is high and the marked level of impairment experienced
      by patients with this disorder is equivalent in magnitude to that reported in
      patients with major depressive disorder. Furthermore, patients with GAD are at
      risk of suicide or suicide attempts, and are frequent users of healthcare
      services. Thus, GAD is a serious and chronic condition that requires appropriate
      long-term treatment. The focus of acute treatment for patients with GAD is the
      improvement of symptoms, while the primary goal of long-term clinical management
      is remission, i.e. the complete resolution of both symptoms and functional
      impairment. The consensus across current treatment guidelines is that first-line
      treatment for patients with GAD should consist of an antidepressant, either a
      selective serotonin reuptake inhibitor (SSRI) such as sertraline, paroxetine or
      escitalopram, or a selective serotonin noradrenaline (norepinephrine) reuptake
      inhibitor (SNRI) such as venlafaxine or duloxetine. However, the SSRIs and SNRIs
      have efficacy limitations, such as lack of response in many patients, a 2- to 4
      week delay before the onset of symptom relief, lack of full remission, and risk
      of relapse. In addition, there are troublesome adverse effects associated with
      both the SSRIs and SNRIs. Evidence from early clinical studies of the atypical
      antipsychotics in the treatment of anxiety and GAD indicate that they may have a
      potential role in the treatment of GAD, either as monotherapy or as augmentation
      to standard treatment.

PMID- 19173370
TI  - Pharmacological manipulation of kynurenic acid: potential in the treatment of
      psychiatric disorders.
AB  - The kynurenine pathway constitutes the main route of tryptophan degradation and
      generates the production of several neuroactive compounds; quinolinic acid is an
      excitotoxic NMDA receptor agonist, 3-hydroxykynurenine is a free-radical
      generator and kynurenic acid (KYNA) is an antagonist at glutamate and nicotinic
      receptors. In low micromolar concentrations, KYNA blocks the glycine site of the
      NMDA receptor and the nicotinic alpha(7) acetylcholine receptor. Knowledge
      regarding kynurenine metabolites and their involvement in neurophysiological
      processes has increased dramatically in recent years. In particular, endogenous
      KYNA appears to tightly control firing of midbrain dopamine neurons and to be
      involved in cognitive functions. Thus, decreased endogenous levels of rat brain
      KYNA have been found to reduce firing of these neurons, and mice with a targeted
      deletion of kynurenine aminotransferase II display low endogenous brain KYNA
      levels concomitant with an increased performance in cognitive tests. It is also
      suggested that kynurenines participate in the pathophysiology of psychiatric
      disorders. Thus, elevated levels of KYNA have been found in the CSF as well as in
      the post-mortem brain of patients with schizophrenia. Advantages in understanding
      how kynurenines can be pharmacologically manipulated may provide new
      possibilities in the treatment of psychiatric disorders, such as schizophrenia.

PMID- 19173372
TI  - Antiepileptic drug-induced cognitive adverse effects: potential mechanisms and
      contributing factors.
AB  - Cognitive dysfunction is frequently observed in patients with epilepsy and
      represents an important challenge in the management of patients with this
      disorder. In this respect, the relative contribution of antiepileptic drugs
      (AEDs) is of relevance. The fact that a considerable number of patients require
      AED therapy for many years, or perhaps even a lifetime, emphasizes the need to
      focus on the long-term adverse effects of these drugs on cognition. The most
      prevalent of the CNS adverse effects observed during AED therapy are sedation,
      somnolence, distractibility, insomnia and dizziness. Sedation, in particular, is
      associated with most of the commonly used AED therapies. Nevertheless, cognitive
      function in individuals with epilepsy may also be influenced by several factors,
      of which AEDs constitute only one of many putative causes. In general terms, most
      studies agree that some differences exist among the older AEDs with regard to the
      effects on cognition, and some newer generation molecules may have a better
      cognitive profile than older AEDs. The mechanisms of action are an obvious
      determinant; however, there is still a lack of evidence for differentiation
      between available drugs with regard to cognitive effects. Some authors have
      suggested that there may be different cognitive effects associated with
      individual drugs; however, the question as to whether there are more specific
      deficits related to the action of individual drugs remains unsolved. There seems
      to be agreement that polytherapy and high-dose treatment can produce cognitive
      adverse effects and when high dosages or adjunctive polytherapy is needed, the
      balance between benefits and disadvantages may be negatively biased against drug
      treatment. Thus, drug treatment requires careful balancing in the attempt to
      reach maximal seizure control while avoiding neurotoxic adverse effects. Finally,
      the mood status of the patient and clinical relevance of the information obtained
      by neuropsychological testing represent important variables that need to be taken
      into account when discussing cognitive adverse effects of AEDs.

PMID- 19173373
TI  - Role of antiepileptic drugs in the management of eating disorders.
AB  - Growing evidence suggests that antiepileptic drugs (AEDs) may be useful in
      managing some eating disorders. In the present paper, we provide a brief overview
      of eating disorders, the rationale for using AEDs in the treatment of these
      disorders and review the data supporting the effectiveness of specific AEDs in
      the treatment of patients with eating disorders. In addition, the potential
      mechanisms of action of AEDs in these conditions are discussed. Of the available
      AEDs, topiramate appears to have the broadest spectrum of action as an anti-binge
      eating, anti-purging and weight loss agent, as demonstrated in two placebo
      controlled studies in bulimia nervosa and three placebo-controlled studies in
      binge-eating disorder (BED) with obesity. Topiramate may also have beneficial
      effects in night-eating syndrome and sleep-related eating disorder, but
      controlled trials in these conditions are needed. The results of one small
      controlled study suggest that zonisamide may have efficacy in BED with obesity.
      However, both topiramate and zonisamide are associated with adverse effect
      profiles that may limit their use in patients with eating disorders. Phenytoin
      may be effective in some patients with compulsive binge eating, particularly if
      co-morbid EEG abnormalities are present, but available data are too varied to
      allow definitive conclusions to be made. Carbamazepine and valproate may be
      effective in treating patients with bulimia nervosa or anorexia nervosa when they
      are used to treat an associated psychiatric (e.g. mood) or neurological (e.g.
      seizure) disorder; otherwise, both agents, particularly valproate, are associated
      with weight gain. In conclusion, AEDs have an emerging role in the management of
      some eating disorders.

PMID- 19173376
TI  - Magneto-mechanical impedance of metallic structures.
AB  - Impedance measurements with a magneto-elastic active sensor are explored for
      inferring the magneto-mechanical impedance (MMI) of a metallic structure. It is
      shown that the MMI contains electrical response of the sensor and both electrical
      and mechanical structural responses. An analytical model is suggested that
      accounts for electrical characteristics of the sensor, sensor/structure
      electromagnetic interaction, and multimodal structural dynamic behavior. The
      model is validated with a set of MMI experiments demonstrating feasibility of
      deducing structural natural frequencies and structural vibration modes.

PMID- 19173375
TI  - Assessing residual confounding of the association between antipsychotic
      medications and risk of death using survey data.
AB  - BACKGROUND: Nonrandomised studies on the causal effects of psychotropic
      medications may be biased by patient characteristics that are not fully adjusted.
      OBJECTIVE: Studies using linked claims databases found that typical antipsychotic
      medications were associated with increased short-term mortality compared with
      atypical antipsychotics. It has been suggested that such results may be due to
      residual confounding by factors that cannot be measured in claims databases.
      Using detailed survey data we identified the direction and magnitude of such
      residual confounding. DESIGN: Cross-sectional survey data. PARTICIPANTS: 17 776
      participants aged > or =65 years from the Medicare Current Beneficiary Survey
      (MCBS). MEASUREMENTS: To determine the association between typical antipsychotic
      use and potential confounding factors we assessed five factors not measured in
      Medicare claims data but in the MCBS, i.e. body mass index, smoking, activities
      of daily living (ADL) score, cognitive impairment and Rosow-Breslau physical
      impairment scale. We estimated adjusted associations between these factors and
      antipsychotic use. Combined with literature estimates of the independent effect
      of confounders on death, we computed the extent of residual confounding caused by
      a failure to adjust for these factors. RESULTS: Comparing typical antipsychotic
      users with atypical antipsychotic users, we found that not adjusting for
      impairments in the ADL score led to an underestimation of the association with
      death (-13%), as did a failure to adjust for cognitive impairment (-7%). The
      combination of all five unmeasured confounders resulted in a net confounding of 
      5% (range -19% to +2%). After correction, the reported association between
      typical antipsychotic use and death compared with atypical antipsychotic use was
      slightly increased from a relative risk (RR) of 1.37 to 1.44 (95% CI 1.33, 1.56).
      Comparing any antipsychotic use with non-users would result in overestimations of
      >50% if cognitive impairment remained unadjusted. CONCLUSION: Claims data studies
      tend to underestimate the association of typical antipsychotics with death
      compared with atypical antipsychotics because of residual confounding by measures
      of frailty. Studies comparing antipsychotic use with non-users may substantially
      overestimate harmful effects of antipsychotics.

PMID- 19173374
TI  - Dopamine dysregulation syndrome: an overview of its epidemiology, mechanisms and
      management.
AB  - Dopamine dysregulation syndrome (DDS) is a relatively recently described
      iatrogenic disturbance that may complicate long-term symptomatic therapy of
      Parkinson's disease. Patients with DDS develop an addictive pattern of dopamine
      replacement therapy (DRT) use, administering doses in excess of those required to
      control their motor symptoms. The prevalence of DDS in patients attending
      specialist Parkinson's disease centres is 3-4%. Amongst the behavioural
      disturbances associated with DDS are punding, which is a complex stereotyped
      behaviour, and impulse control disorders (ICDs), such as pathological gambling,
      hypersexuality, compulsive shopping and compulsive eating. We review the risk
      factors and potential mechanisms for the development of DDS, including
      personality traits, potential genetic influences and Parkinson's disease-related
      cognitive deficits. Impulsive personality traits are prominent in patients
      developing DDS, and have been previously associated with the development of
      substance dependence. Candidate genes affecting the dopamine 'D(2)-like' receptor
      family have been associated with impulsive personality traits in addition to drug
      and nondrug addictions. Impaired decision making is implicated in addictive
      behaviours, and decision-making abilities can be influenced by dopaminergic
      medications. In Parkinson's disease, disruption of the reciprocal loops between
      the striatum and structures in the prefrontal cortex following dopamine depletion
      may predispose to DDS. The role of DRT in DDS is discussed, with particular
      reference to models of addiction, suggesting that compulsive drug use is due to
      progressive neuroadaptations in dopamine projections to the accumbens-related
      circuitry. Evidence for neuroadaptations and sensitization occurring in DDS
      include enhanced levodopa-induced ventral striatal dopamine release. Levodopa is
      still considered the most potent trigger for DDS in Parkinson's disease, but
      subcutaneous apomorphine and oral dopamine agonists may also be responsible. In
      the management of DDS, further research is needed to identify at-risk groups,
      thereby facilitating more effective early intervention. Therefore, an increased
      awareness of the syndrome amongst treating physicians is vital. Medication
      reduction strategies are employed, particularly with regard to avoiding rapidly
      acting 'booster' DRT formulations. Psychosocial treatments, including cognitive
      behavioural therapy, have been beneficial in treating substance use disorders and
      ICDs in non-Parkinson's disease patients, but there are currently no published
      trials of psychological interventions in DDS. Further studies are also required
      to identify factors that can predict those patients with DDS or ICDs who will
      derive benefit from surgical interventions such as deep brain stimulation.

PMID- 19173377
TI  - Time-forward speech intelligibility in time-reversed rooms.
AB  - The effects of time-reversed room acoustics on word recognition abilities were
      examined using virtual auditory space techniques, which allowed for temporal
      manipulation of the room acoustics independent of the speech source signals. Two
      acoustical conditions were tested: one in which room acoustics were simulated in
      a realistic time-forward fashion and one in which the room acoustics were
      reversed in time, causing reverberation and acoustic reflections to precede the
      direct-path energy. Significant decreases in speech intelligibility--from 89% on
      average to less than 25%--were observed between the time-forward and time
      reversed rooms. This result is not predictable using standard methods for
      estimating speech intelligibility based on the modulation transfer function of
      the room. It may instead be due to increased degradation of onset information in
      the speech signals when room acoustics are time-reversed.

PMID- 19173378
TI  - Sequential effects on the detectability of a tone added to a multitone masker.
AB  - The detectability of a tone added to a masker is superior when the detection
      trial is preceded by the masker than the signal-plus-masker. This auditory
      enhancement can withstand long temporal gaps between the precursor and the trial,
      suggesting that for yes/no trials sensitivity may depend on the stimulus
      presented in the prior trial. The results from an experiment examining the
      detectability of a 1000-Hz tone added to 6-tone maskers confirmed sequential
      effects on sensitivity. The values of d(') were higher when the prior trial was a
      no-signal (masker alone) trial compared to a signal (signal-plus-masker) trial.

PMID- 19173379
TI  - Speaking up: Killer whales (Orcinus orca) increase their call amplitude in
      response to vessel noise.
AB  - This study investigated the effects of anthropogenic sound exposure on the vocal
      behavior of free-ranging killer whales. Endangered Southern Resident killer
      whales inhabit areas including the urban coastal waters of Puget Sound near
      Seattle, WA, where anthropogenic sounds are ubiquitous, particularly those from
      motorized vessels. A calibrated recording system was used to measure killer whale
      call source levels and background noise levels (1-40 kHz). Results show that
      whales increased their call amplitude by 1 dB for every 1 dB increase in
      background noise levels. Furthermore, nearby vessel counts were positively
      correlated with these observed background noise levels.

PMID- 19173380
TI  - Threshold fine structure affects amplitude modulation perception.
AB  - Modulation detection thresholds of a sinusoidally amplitude-modulated tone were
      measured for two different positions of the low-level carrier relative to the
      fine structure of the threshold in quiet. Modulation detection thresholds were
      higher for a carrier at a fine-structure minimum than for a carrier at a fine
      structure maximum, regardless of whether the carriers had the same sound pressure
      level or the same sensation level. This indicates that even for small variations
      of the carrier frequency, the sensitivity to amplitude modulation can vary
      substantially due to the frequency characteristics of the threshold in quiet.

PMID- 19173381
TI  - Monitoring progressive damage in polymer-based composite using nonlinear dynamics
      and acoustic emission.
AB  - In this work quantitative results of applying nonlinear acoustic dynamics to
      study progressive damage in a polymer-based composite SMC (sheet molding
      compound) are presented. Via carefully controlled resonant plate experiment,
      nonlinear slow dynamics (SNLD) response of SMC in terms of relaxation time and
      frequency shift has been shown to be very sensitive to gradual damage induced
      using three-point bending tests. Besides, acoustic emission monitoring is used to
      characterize damage through the elastic energy released by SMC at every damage
      step. Interesting logarithmlike changes of the SNLD parameters as a function of
      the acoustic emission cumulated energy are found.

PMID- 19173382
TI  - Observations of low-frequency temporal and spatial coherence in shallow water.
AB  - Measurements of temporal and spatial coherence are most always confounded by the
      presence of multipath interference. Here, two sets of data are presented that
      allow separation of arrivals from individual propagating modes and then
      unambiguous computations of temporal and spatial coherence free of multipath
      effects. A consistent finding for surface reflected bottom reflected (SRBR) modes
      is that lower order mode are more coherent in both time and space than higher
      order (steeper) modes. Also, SRBR paths are much more coherent than refracted
      bottom reflected mode groups that cannot be separated in time and are affected by
      multi-mode interference.

PMID- 19173383
TI  - Modulation frequency features for phoneme recognition in noisy speech.
AB  - In this letter, a new feature extraction technique based on modulation spectrum
      derived from syllable-length segments of subband temporal envelopes is proposed.
      These subband envelopes are derived from autoregressive modeling of Hilbert
      envelopes of the signal in critical bands, processed by both a static
      (logarithmic) and a dynamic (adaptive loops) compression. These features are then
      used for machine recognition of phonemes in telephone speech. Without degrading
      the performance in clean conditions, the proposed features show significant
      improvements compared to other state-of-the-art speech analysis techniques. In
      addition to the overall phoneme recognition rates, the performance with broad
      phonetic classes is reported.

PMID- 19173384
TI  - Comments on work published elsewhere.

PMID- 19173385
TI  - Toward the acoustical characterization of asphalt pavements: analysis of the
      tire/road sound from a porous surface.
AB  - Sound level in close proximity to the contact patch of the tire and road
      (L(CPtr)) is analyzed as a function of the vehicle speed in the acoustic
      frequency range, showing different behavior depending on frequency. At least two
      regions are observed; one at low frequencies, where the variation in sound with
      speed (coefficient B) increases with frequency, and the other at higher
      frequencies, where such sound/speed variation does not increase significantly
      with frequency. The dependence of B at low frequencies seems to be correlated
      with the high sound absorption of this porous surface.

PMID- 19173386
TI  - Feasibility of global-scale synthetic aperture communications.
AB  - A recent paper [Higley et al., J. Acoust. Soc. Am. 118, 2365-2372 (2005)]
      investigated synthetic aperture communications in shallow water exploiting the
      relative motion between a source and a receiver. This letter presents a
      feasibility study of synthetic aperture communications at global distances using
      the 57 Hz acoustic data from the Heard Island Feasibility Test conducted in
      January 1991 [Baggeroer and Munk, Phys. Today 45, 22-30 (1992)]. Specifically, a
      reception at Ascension Island, about 9200 km from the source ship moving at about
      3 kt near Heard Island, is analyzed by treating the 255-digit m-sequence
      tomography signal as a binary-phase shift-keying communication signal with an
      information rate of 11.4 bitss. The performance using a single receiver combining
      three consecutive receptions spaced 5.2 min ( approximately 470 m) apart
      indicates that synthetic aperture acoustic communications is feasible at global
      distances.

PMID- 19173387
TI  - Comment on "Measuring power production in the mammalian cochlea" [Curr. Biol. 17,
      1340 (2007)].
AB  - Recently, a paper by Lakashkin et al. (2007) ("Power amplification in the
      mammalian cochlea," Curr. Biol. 17, 1340-1344) was published on how power can be
      measured in the mammalian cochlea. The general subject is of current widespread
      interest, so the question of whether the method used by Lakashkin et al. is valid
      may be of interest to the readers of this journal. Power generation in the
      cochlea can account for the extraordinary sensitivity of hearing. Lukashkin et
      al. claimed to provide a direct proof of cochlear power generation. A first-order
      spring-dashpot system was used to model the organ of Corti. The power flux
      direction can be derived from the sign of the phase difference between the force
      and displacement, which can be presented as a "hysteresis plot." Basilar membrane
      (BM) vibration near the characteristic frequency (CF) was measured while applying
      a low-frequency modulation tone together with the CF tone. A force was derived
      from the modulation profile of the BM CF vibration and when plotted versus the
      displacement at the modulation frequency, the function had a counterclockwise
      direction of hysteresis, suggesting power generation. In this letter, we present
      comments on the analysis in the report: (1) that it is not appropriate to analyze
      at the modulation frequency to derive the power generation at CF; (2) that the
      derivation of a force from just the displacement profile is not justified,
      followed by an alternative interpretation of the experimental data.

PMID- 19173388
TI  - Reduced contribution of a nonsimultaneous mistuned harmonic to residue pitch: the
      role of harmonic number.
AB  - Listeners adjusted a matching sound so that its pitch equaled that of a
      subsequent 90-ms complex tone (12 harmonics of a 155-Hz F0), whose mistuned
      harmonic (+/-3%) was presented either simultaneously with or after the other
      harmonics. The third or the fourth harmonic was mistuned. For both harmonics,
      pitch shifts were significantly smaller when the mistuned harmonic was presented
      after rather than simultaneously with the remainder of the target complex and
      when the component corresponding to the mistuned harmonic was absent (as opposed
      to present) from the matching sound. Presenting the mistuned component after the
      remainder of the complex generally reduced the pitch shifts more for the third
      than for the fourth harmonic; the nonsimultaneous presentation reduced shifts by
      a factor of 2.8 (third) and 1.7 (fourth) in the presence, and 6.4 (third) and 1.9
      (fourth) in the absence of the nominally mistuned harmonic from the matching
      sound. The results are discussed in terms of an analytical listening and matching
      strategy that results in larger pitch shifts for a nonsimultaneous mistuned
      harmonic that has an octave or double-octave relationship to the F0 than for one
      that does not, without it necessarily being temporally integrated into the
      residue pitch of the complex.

PMID- 19173389
TI  - Identification of synthetic vowels based on selected vocal tract area functions.
AB  - The purpose of this study was to determine the degree to which synthetic vowel
      samples based on previously reported vocal tract area functions of eight speakers
      could be accurately identified by listeners. Vowels were synthesized with a wave
      reflection type of vocal tract model coupled to a voice source. A particular
      vowel was generated by specifying an area function that had been derived from
      previous magnetic resonance imaging based measurements. The vowel samples were
      presented to ten listeners in a forced choice paradigm in which they were asked
      to identify the vowel. Results indicated that the vowels [i], [ae], and [u] were
      identified most accurately for all of speakers. The identification errors of the
      other vowels were typically due to confusions with adjacent vowels.

PMID- 19173390
TI  - An analysis of the masking of speech by competing speech using self-report data.
AB  - Many of the items in the "Speech, Spatial, and Qualities of Hearing" scale
      questionnaire [S. Gatehouse and W. Noble, Int. J. Audiol. 43, 85-99 (2004)] are
      concerned with speech understanding in a variety of backgrounds, both speech and
      nonspeech. To study if this self-report data reflected informational masking,
      previously collected data on 414 people were analyzed. The lowest scores
      (greatest difficulties) were found for the two items in which there were two
      speech targets, with successively higher scores for competing speech (six items),
      energetic masking (one item), and no masking (three items). The results suggest
      significant masking by competing speech in everyday listening situations.

PMID- 19173391
TI  - Abnormal processing of temporal fine structure in speech for frequencies where
      absolute thresholds are normal.
AB  - The identification of nonsense syllables that were lowpass filtered at 1.5 kHz
      was compared for subjects with normal hearing and subjects with mild-to-severe
      hearing loss at high frequencies but with normal or near-normal hearing at low
      frequencies. Absolute thresholds were mostly within the normal range (<20 dB
      hearing level) for both groups for frequencies below 1.5 kHz. Performance was
      assessed with intact speech, speech that had been processed to preserve only
      temporal envelope cues in a few frequency bands (E speech), and speech that had
      been processed to remove envelope cues as far as possible while preserving
      temporal fine structure cues, again in a few frequency bands (TFS speech). For
      the intact speech and E speech, the hearing-impaired subjects performed slightly
      more poorly than the normal-hearing subjects, but this effect was significant
      only for the intact speech. For the TFS speech, the hearing-impaired subjects
      performed significantly more poorly than the normal-hearing subjects, with 12 out
      of 16 of the former performing at chance. The results indicate that, for people
      with hearing loss at medium to high frequencies, the processing of the TFS of
      speech can be degraded for frequencies where absolute thresholds are within the
      normal range.

PMID- 19173392
TI  - Sound transmission loss of rectangular and slit-shaped apertures: experimental
      results and correlation with a modal model.
AB  - Among noise control techniques, enclosures are widely used. It is known that
      enclosure acoustic efficiency is strongly influenced by the presence of openings
      or leaks. Modeling of diffuse field sound transmission loss (TL) of apertures and
      slits is therefore critical when the enclosure acoustic performance
      characteristics need to be predicted with confidence either for design or for
      modifying existing enclosures. Recently, a general model for diffuse field sound
      TL of rectangular and circular apertures has been developed and validated with
      respect to existing analytical or numerical models. This paper presents an
      experimental validation of this new model. The aim was to develop a simple,
      reliable tool for predicting enclosure insertion loss using statistical energy
      analysis. Twelve out of the 15 test configurations were found to be reliable and
      were compared with theoretical models, which in fact correlate closely (without
      adjustment) with the experimental work.

PMID- 19173393
TI  - T-matrix methods in acoustic scattering.
AB  - Some further refinements are described for the T-matrix approach to acoustic
      scattering. From the structure of the matrices involved, one can infer the
      Rayleigh limit explicitly for objects having no density contrast. One finds
      T(Ray)=iR-R(2), where the R-matrix involves integrals of the regular spherical
      wave functions over the object's surface. The index of refraction and loss factor
      can be chosen as desired, and energy balance and reciprocity requirements are
      found to be met. The derivation can be extended to obtain the Rayleigh expansion,
      effectively describing T as a series in ascending powers of the ratio of object
      size to wavelength. In trial cases, the series converges throughout the Rayleigh
      region and somewhat beyond. Bodies of high aspect ratio are also considered,
      where difficulties arise due to precision loss during numerical integration. Loss
      ranges from 4 or 5 significant figures (2:1 spheroid) to 22 figures (40:1
      spheroid) or more. A class of surfaces has been found for which this problem can
      be avoided, however, enabling one to treat a variety of body shapes up to aspect
      ratios of 100:1 with no difficulty.

PMID- 19173394
TI  - Three-dimensional propagation and scattering around a conical seamount.
AB  - A three-dimensional (3D) propagation and scattering model is developed for an
      offset acoustic source in an ocean with axisymmetric bathymetry. Based on the
      same theoretical foundation as the formulation presented by Taroudakis [M. I.
      Taroudakis, "A coupled-mode formulation for the solution in the presence of a
      conical sea-mount," J. Comput. Acoust. 4, 101-121 (1996)], the present approach
      combines a spectral decomposition in azimuth with a coupled-mode theory for two
      way, range-dependent propagation. However, the earlier formulations were severely
      limited in terms of frequency, size, and geometry of the seamount, the seabed
      composition, and the distance between the source and the seamount, and were
      therefore severely limited in regard to realistic seamount problems. Without
      changing the fundamental theoretical foundation, the present approach applies a
      number of modifications to the numerical formulation, leading to orders of
      magnitude in numerical efficiency for realistic problems. Further, by using a
      standard normal mode model for determining the fundamental modal solutions and
      coupling matrices, and by applying a simple superposition principle, the
      computational requirements are made independent of the distance between the
      seamount and the source and receivers, and dependent only on the geometry of the
      seamount and the source frequency. Therefore, realistic propagation and
      scattering scenarios can be modeled, including effects of seamount roughness and
      realistic sedimentary structure.

PMID- 19173395
TI  - Reflection of underwater sound from surface waves.
AB  - A tank experiment has been conducted to measure reflection of underwater sound
      from surface waves. Reflection from a wave crest leads to focusing and caustics
      and results in rapid variation in the received waveform as the surface wave
      moves. Theoretical results from wavefront modeling show that interference of
      three surface reflected eigenrays for each wave crest produces complicated
      interference waveforms. There is good agreement between theory and experiment
      even on the shadow side of caustics where there are two surface reflected
      arrivals but only one eigenray.

PMID- 19173396
TI  - Use of the distorted wave born approximation to predict scattering by
      inhomogeneous objects: application to squid.
AB  - A new method has been developed to predict acoustic scattering by weakly
      scattering objects with three-dimensional variability in sound speed and density.
      This variability can take the form of inhomogeneities within the body of the
      scatterer and/or geometries where the acoustic wave passes through part of the
      scattering body, into the surrounding medium, and back into the body. This method
      applies the distorted wave Born approximation (DWBA) using a numerical approach
      that rigorously accounts for the phase changes within a scattering volume. Ranges
      of validity with respect to material properties and numerical considerations are
      first explored through comparisons with modal-series-based predictions of
      scattering by fluid-filled spherical and cylindrical fluid shells. The method is
      then applied to squid and incorporates high resolution spiral computerized
      tomography (SCT) scans of the complex morphology of the organism. Target strength
      predictions based on the SCT scans are compared with published backscattering
      data from live, freely swimming and tethered squid. The new method shows
      significant improvement for both single-orientation and orientation-averaged
      scattering predictions over the DWBA-homogeneous-prolate-spheroid model.

PMID- 19173397
TI  - Benchmark problems for acoustic scattering from elastic objects in the free field
      and near the seafloor.
AB  - Results from a workshop organized in 2006 to assess the state of the art in
      target scatter modeling are presented. The problem set includes free-field
      scenarios as well as scattering from targets that are proud, half-buried, or
      fully buried in the sediment. The targets are spheres and cylinders, of size O(1
      m), which are insonified by incident plane waves in the low-frequency band 0.1-10
      kHz. In all cases, the quantity of interest is the far-field target strength. The
      numerical techniques employed fall within three classes: (i) finite-element (FE)
      methods and (ii) boundary-element (BE) techniques, with different approaches to
      computing the far field via discretizations of the Helmholtz-Kirchhoff integral
      in each case, and (iii) semianalytical methods. Reference solutions are
      identified for all but one of the seven test problems considered. Overall, FE-
      and BE-based models emerge as those being capable of treating a wider class of
      problems in terms of target geometry, with the FE method having the additional
      advantage of being able to deal with complex internal structures without much
      additional effort. These capabilities are of value for the study of experimental
      scenarios, which can essentially be envisioned as variations of the problem set
      presented here.

PMID- 19173398
TI  - Coherence function of a sound field in an oceanic waveguide with horizontally
      isotropic statistics.
AB  - The mean value and the coherence function of a sound field propagating in an
      oceanic waveguide with random inhomogeneities are important statistical
      characteristics of this field, which are needed for many practical applications.
      Closed equations for the coherence function were obtained in many works for both
      two dimensional and three dimensional geometries. For the 3D case, these
      equations are too involved even for a numerical treatment. In this paper,
      explicit expressions for the mean field and the coherence function due to a point
      omnidirectional monochromatic source in a 3D waveguide are derived for the case
      of random inhomogeneities, which are statistically isotropic in a horizontal
      plane. The solutions are much simpler than those obtained previously due to the
      cylindrical symmetry of the problem. The theory developed is used to study
      numerically the mean field and the coherence function in an oceanic waveguide
      perturbed by a random field of internal waves with the Garrett-Munk spectrum.

PMID- 19173399
TI  - Empirical dependence of acoustic transmission scintillation statistics on
      bandwidth, frequency, and range in New Jersey continental shelf.
AB  - The scintillation statistics of broadband acoustic transmissions are determined
      as a function of signal bandwidth B, center frequency f(c), and range with
      experimental data in the New Jersey continental shelf. The received signal
      intensity is shown to follow the Gamma distribution implying that the central
      limit theorem has led to a fully saturated field from independent multimodal
      propagation contributions. The Gamma distribution depends on the mean intensity
      and the number of independent statistical fluctuations or coherent cells micro of
      the received signal. The latter is calculated for the matched filter, the
      Parseval sum, and the bandpassed center frequency, all of which are standard
      ocean acoustic receivers. The number of fluctuations mu of the received signal is
      found to be an order of magnitude smaller than the time-bandwidth product TB of
      the transmitted signal, and to increase monotonically with relative bandwidth
      Bfc. A computationally efficient numerical approach is developed to predict the
      mean intensity and the corresponding broadband transmission loss of a
      fluctuating, range-dependent ocean waveguide by range and depth averaging the
      output of a time-harmonic stochastic propagation model. This model enables
      efficient and accurate estimation of transmission loss over wide areas, which has
      become essential in wide-area sonar imaging applications.

PMID- 19173400
TI  - Cooperative prey herding by the pelagic dolphin, Stenella longirostris.
AB  - Sonar techniques were used to quantitatively observe foraging predators and their
      prey simultaneously in three dimensions. Spinner dolphins foraged at night in
      highly coordinated groups of 16-28 individuals using strict four-dimensional
      patterns to increase prey density by up to 200 times. Herding exploited the
      prey's own avoidance behavior to achieve food densities not observed otherwise.
      Pairs of dolphins then took turns feeding within the aggregation that was
      created. Using a proxy estimate of feeding success, it is estimated that each
      dolphin working in concert has more access to prey than it would if feeding
      individually, despite the costs of participating in the group maneuvers,
      supporting the cooperation hypothesis. Evidence of a prey density threshold for
      feeding suggests that feedback from the environment may be enough to favor the
      evolution of cooperation. The remarkable degree of coordination shown by foraging
      spinner dolphins, the very strict geometry, tight timing, and orderly turn
      taking, indicates the advantage conferred by this strategy and the constraints
      placed upon it. The consistent appearance of this behavior suggests that it may
      be a critical strategy for energy acquisition by spinner dolphins in energy poor
      featureless environments in the tropical Pacific Ocean.

PMID- 19173401
TI  - Fuzzy structure theory modeling of sound-insulation layers in complex
      vibroacoustic uncertain systems: theory and experimental validation.
AB  - The fuzzy structure theory was introduced 20 years ago in order to model the
      effects of complex subsystems imprecisely known on a master structure. This
      theory was only aimed at structural dynamics. In this paper, an extension of that
      theory is proposed in developing an elastoacoustic element useful to model sound
      insulation layers for computational vibroacoustics of complex systems. The
      simplified model constructed enhances computation time and memory allocation
      because the number of physical and generalized degrees of freedom in the
      computational vibroacoustic model is not increased. However, these
      simplifications introduce model uncertainties. In order to take into account
      these uncertainties, the nonparametric probabilistic approach recently introduced
      is used. A robust simplified model for sound-insulation layers is then obtained.
      This model is controlled by a small number of physical and dispersion parameters.
      First, the extension of the fuzzy structure theory to elastoacoustic element is
      presented. Second, the computational vibroacoustic model including such an
      elastoacoustic element to model sound-insulation layer is given. Then, a design
      methodology to identify the model parameters with experiments is proposed and is
      experimentally validated. Finally, the theory is applied to an uncertain
      vibroacoustic system.

PMID- 19173402
TI  - Wave characterization of cylindrical and curved panels using a finite element
      method.
AB  - This paper describes a wave finite element method for the numerical prediction of
      wave characteristics of cylindrical and curved panels. The method combines
      conventional finite elements and the theory of wave propagation in periodic
      structures. The mass and stiffness matrices of a small segment of the structure,
      which is typically modeled using either a single shell element or, especially for
      laminated structures, a stack of solid elements meshed through the cross-section,
      are postprocessed using periodicity conditions. The matrices are typically found
      using a commercial FE package. The solutions of the resulting eigenproblem
      provide the frequency evolution of the wavenumber and the wave modes. For
      cylindrical geometries, the circumferential order of the wave can be specified in
      order to define the phase change that a wave experiences as it propagates across
      the element in the circumferential direction. The method is described and
      illustrated by application to cylinders and curved panels of different
      constructions. These include isotropic, orthotropic, and laminated sandwich
      constructions. The application of the method is seen to be straightforward even
      in the complicated case of laminated sandwich panels. Accurate predictions of the
      dispersion curves are found at negligible computational cost.

PMID- 19173403
TI  - Generalized eigenfunctions of layered elastic media and application to diffuse
      fields.
AB  - The spectral decomposition of the elastic wave operator in a layered isotropic
      half-space is derived by means of standard functional analysis methods.
      Particular attention is paid to the coupled P-SV waves. The problem is formulated
      directly in terms of displacements which leads to a 2 x 2 Sturm-Liouville system.
      The resolvent kernel (Green's function) is expressed in terms of simple plane
      wave solutions. Application of Stone's formula leads naturally to eigenfunction
      expansions in terms of generalized eigenvectors with oscillatory behavior at
      infinity. The generalized eigenfunction expansion is employed to define a diffuse
      field as a white noise process in modal space. By means of a Wigner transform, we
      calculate vertical to horizontal kinetic energy ratios in layered media, as a
      function of depth and frequency. Several illustrative examples are considered
      including energy ratios near a free surface, in the presence of a soft layer.
      Numerical comparisons between the generalized eigenfunction summation and a
      classical locked-mode approximation demonstrate the validity of the approach. The
      impact of the local velocity structure on the energy partitioning of a diffuse
      field is illustrated.

PMID- 19173404
TI  - Minimizing sleep disturbance from blast noise producing training activities for
      residents living near a military installation.
AB  - Field research was conducted during 2004 in the vicinity of a United States
      military installation to determine if awakening of residents due to blast noise
      from large military weapons might vary during the night. Analysis of the data
      indicates that awakening from blast noise is significantly less likely during the
      time period between midnight and 0200 h compared to time periods before midnight
      and approaching dawn. These findings suggest that postponing noisy evening
      training until after midnight could effectively reduce the negative impact of
      nighttime training on local residents and thus help to preserve nighttime
      training capabilities.

PMID- 19173405
TI  - Measuring hybrid passive-active sound absorption of a microperforated liner at
      oblique incidence.
AB  - The performance of hybrid passive-active absorbers at normal incidence has been
      previously demonstrated. However, their feasibility in realistic environments
      remains to be confirmed. This paper proposes a hybrid passive-active liner
      absorbing at oblique incidence. The passive absorber is a 2.44x2.44x1 mm(3)
      microperforated panel backed by a 5 cm deep air layer and a rigid ending. An
      active multichannel cell, composed of five single-input single-output
      controllers, releases the sound pressure at the entrance of the air cavity in a
      reduced area of the microperforated panel absorber. Hybrid passive/active
      absorption of the prototype is measured in an anechoic room up to a maximum
      incidence angle of 21 degrees . For instance, at 20 degrees such a system is able
      to provide an average absorption of 94% between 266 and 1500 Hz. In addition, the
      performance that would provide such a hybrid absorber in a reverberant room has
      been quantified theoretically by an index describing the active-to-passive
      reverberation time ratio in terms of the active-to-passive absorption area and
      absorption coefficient ratios. The proposed prototype, implementing 7% of the
      active proportion area, would afford a reverberation time reduction between 77.5%
      and 12% from 100 to 500 Hz.

PMID- 19173406
TI  - A broadband fast multipole accelerated boundary element method for the three
      dimensional Helmholtz equation.
AB  - The development of a fast multipole method (FMM) accelerated iterative solution
      of the boundary element method (BEM) for the Helmholtz equations in three
      dimensions is described. The FMM for the Helmholtz equation is significantly
      different for problems with low and high kD (where k is the wavenumber and D the
      domain size), and for large problems the method must be switched between levels
      of the hierarchy. The BEM requires several approximate computations (numerical
      quadrature, approximations of the boundary shapes using elements), and these
      errors must be balanced against approximations introduced by the FMM and the
      convergence criterion for iterative solution. These different errors must all be
      chosen in a way that, on the one hand, excess work is not done and, on the other,
      that the error achieved by the overall computation is acceptable. Details of
      translation operators for low and high kD, choice of representations, and BEM
      quadrature schemes, all consistent with these approximations, are described. A
      novel preconditioner using a low accuracy FMM accelerated solver as a right
      preconditioner is also described. Results of the developed solvers for large
      boundary value problems with 0.0001 less, similarkD less, similar500 are
      presented and shown to perform close to theoretical expectations.

PMID- 19173407
TI  - Space domain complex envelopes: definition and a spatial modulation method.
AB  - When one visualizes a sound field as a means of treating noise sources, a
      detailed variation of the sound field is not required. It is sufficient to see
      source locations and overall variation of the field. A complex envelope in space
      can provide adequate information that one wishes to get because an envelope shows
      a gross change in signal. In other words, to interpret overall variation of sound
      fields in terms of a complex envelope is attempted. To achieve this objective,
      spatial complex envelopes have been defined firstly, and then a spatial
      modulation method to obtain the envelope has been theoretically developed and
      verified.

PMID- 19173408
TI  - Basin-scale time reversal communications.
AB  - During November 1994, broadband acoustic signals were transmitted from a 75-Hz
      source to a 20-element, 700-m vertical array at approximately 3250 km range in
      the eastern North Pacific Ocean as part of the acoustic engineering test (AET) of
      the acoustic thermometry of ocean climate program [Worcester et al., J. Acoust.
      Soc. Am. 105, 3185-3201 (1999)]. The AET tomography signal can be treated as a
      binary-phase shift-keying communication signal with an information rate of 37.5
      bitss. With the multipath arrivals spanning 5-8 sec, these data represent an
      extreme case of intersymbol interference. The AET array data are processed using
      time reversal combined with frequent channel updates to accommodate channel
      variations over the 20-min long reception, followed by a single channel decision
      feedback equalizer. The almost error-free performance using all 20 array elements
      demonstrates the feasibility of time reversal communications at basin scale.
      Further, comparable performance of single receive element communications
      integrating over multiple transmissions indicates that the ocean provided
      temporal diversity that is as effective as the spatial diversity provided by the
      array.

PMID- 19173409
TI  - The prolate spheroidal wave functions as invariants of the time reversal operator
      for an extended scatterer in the Fraunhofer approximation.
AB  - The decomposition of the time reversal operator, known by the French acronym
      DORT, is widely used to detect, locate, and focus on scatterers in various
      domains such as underwater acoustics, medical ultrasound, and nondestructive
      evaluation. In the case of point-scatterers, the theory is well understood: The
      number of nonzero eigenvalues is equal to the number of scatterers, and the
      eigenvectors correspond to the scatterers Green's function. In the case of
      extended objects, however, the formalism is not as simple. It is shown here that,
      in the Fraunhofer approximation, analytical solutions can be found and that the
      solutions are functions called prolate spheroidal wave-functions. These functions
      have been studied in information theory as a basis of band-limited and time
      limited signals. They also arise in optics. The theoretical solutions are
      compared to simulation results. Most importantly, the intuition that for an
      extended objects, the number of nonzero eigenvalues is proportional to the number
      of resolution cell in the object is justified. The case of three-dimensional
      objects imaged by a two-dimensional array is also dealt with. Comparison with
      previous solutions is made, and an application to super-resolution of scatterers
      is presented.

PMID- 19173410
TI  - A phase and space coherent direct imaging method.
AB  - A direct imaging algorithm for point and extended targets is presented. The
      algorithm is based on a physical factorization of the response matrix of a
      transducer array. The factorization is used to transform a passive target problem
      to an active source problem and to extract principal components (tones) in a
      phase consistent way. The multitone imaging function can superpose multiple tones
      (spatial diversity/aperture of the array) and frequencies (bandwidth of the
      probing signal) based on phase coherence. The method is a direct imaging
      algorithm that is simple and efficient since no forward solver or iteration is
      needed. Robustness of the algorithm with respect to noise is demonstrated via
      numerical examples.

PMID- 19173412
TI  - Psychophysical and physiological measures of electrical-field interaction in
      cochlear implants.
AB  - The primary purpose of this study was to determine whether the electrically
      evoked compound action potential (ECAP) can be used to predict psychophysical
      electrical-field interaction patterns obtained with simultaneous stimulation of
      intracochlear electrodes. The second goal was to determine whether ECAP patterns
      are affected by recording location because differences might influence the
      relation between ECAP and psychophysical measures. The third goal was to
      investigate whether symmetrical threshold shifts are produced with phase
      inversion of the interaction stimulus. Nine adults with Advanced Bionics cochlear
      implants participated. ECAP and psychophysical thresholds were obtained for
      basal, middle, and apical probe electrodes in the presence of a subthreshold
      interaction stimulus delivered simultaneously to each of seven to eight
      interaction electrodes per probe. The results showed highly significant
      correlations between ECAP and psychophysical threshold shifts for all nine
      subjects, which suggests that the ECAP can adequately predict psychophysical
      electrical-field interaction patterns for subthreshold stimuli. ECAP thresholds
      were significantly higher for recordings from the basal (versus apical) side of
      the probe, which suggests that recording location may affect relations between
      ECAP and psychophysical measures. Interaction stimulus phase inversion generally
      produced symmetrical threshold shifts for psychophysical measures but not for
      half of ECAP measures.

PMID- 19173411
TI  - Sex differences in distortion-product and transient-evoked otoacoustic emissions
      compared.
AB  - Although several studies have documented the existence of sex differences in
      spontaneous otoacoustic emissions (SOAEs) and transient-evoked OAEs (TEOAEs) in
      humans, less has been published about sex differences in distortion-product OAEs
      (DPOAEs). Estimates of sex and ear differences were extracted from a data set of
      OAE measurements previously collected for other purposes. In accord with past
      findings, the sex differences for TEOAEs were substantial for both narrowband and
      wideband measures. By contrast, the sex differences for DPOAEs were about half
      the size of those for TEOAEs. In this sample, the ear differences were small for
      TEOAEs in both sexes and absent for DPOAEs. One implication is that the cochlear
      mechanisms underlying DPOAEs appear to be less susceptible to whatever influences
      are responsible for producing sex differences in TEOAEs and SOAEs in humans. We
      discuss the possibility that differences in the effective level of the stimuli
      may contribute to these outcomes.

PMID- 19173413
TI  - Spectral and temporal integration of brief tones.
AB  - Both spectral and temporal integration of tones have been explored in detail, but
      integration of tones varying across both dimensions has received little
      attention. This study explores temporal integration of tone pulses that vary over
      a range of frequencies. Baseline thresholds were obtained for both spectral and
      temporal integration with the same signals and compared with prior research. The
      signals were then varied on both dimensions in several ways: with equivalent
      spectral and temporal step sizes, different spectral and temporal step sizes, and
      a random pattern of frequency presentation. The data were also analyzed by
      spectral step size, temporal step size, frequency range, direction and slope of
      frequency change, and predictability. The spectral and temporal integration
      conditions showed that the current procedures and signals yielded the same
      improvement in detection thresholds as prior studies. The spectrotemporal
      integration conditions showed the improvement for overall detection of the
      signals to be limited by spectral integration, with improvement related primarily
      to the number of tones, regardless of timing and frequency. Surprisingly, trial
      by-trial random presentation of signal frequencies did not negatively influence
      detection. These results support the multiple looks hypothesis [Viemeister, N. F.
      and Wakefield, G. H. (1991). "Temporal integration and multiple looks," J.
      Acoust. Soc. Am. 90, 858-865] as applied to spectrotemporal integration.

PMID- 19173415
TI  - Within- and across-channel factors in the multiband comodulation masking release
      paradigm.
AB  - Maskers made up of comodulated narrow bands of noise can result in a signal
      detection advantage due to both within- and across-channel processes. The purpose
      of this study was to determine whether contributions from these processes could
      be differentiated on the basis of two stimulus manipulations: (1) onset/offset
      asynchrony across bands and (2) introduction of a random temporal fringe
      surrounding the comodulated bands. The hypothesis was that only masking release
      due to across-channel processing would be disrupted by these manipulations. Five
      band comodulated maskers were constructed, and the availability of within- and
      across-channel cues was varied by adjusting the frequency spacing of the bands;
      both logarithmic and linear spacings were tested. The signal was a 1 kHz pure
      tone. Onset/offset asynchrony had different effects depending on the
      characteristics of the asynchrony. The results were consistent with an
      interpretation that across-channel, but not within-channel, masking release was
      disrupted when the flanking bands were presented continuously and the on-signal
      band was gated. However, the results suggested that both the across-channel and
      the within-channel masking release were disrupted in conditions where the on
      signal band was continuous and the flanking bands were gated on, as well as in
      conditions where a random temporal fringe was present.

PMID- 19173414
TI  - Pitfalls in behavioral estimates of basilar-membrane compression in humans.
AB  - Psychoacoustic estimates of basilar-membrane compression often compare on- and
      off-frequency forward masking. Such estimates involve assuming that the recovery
      from forward masking for a given signal frequency is independent of masker
      frequency. To test this assumption, thresholds for a brief 4-kHz signal were
      measured as a function of masker-signal delay. Comparisons were made between on
      frequency (4 kHz) and off-frequency (either 2.4 or 4.4 kHz) maskers, adjusted in
      level to produce the same amount of masking at a 0-ms delay between masker offset
      and signal onset. Consistent with the assumption, forward-masking recovery from a
      moderate-level (83 dB SPL) 2.4-kHz masker and a high-level (92 dB SPL) 4.4-kHz
      masker was the same as from the equivalent on-frequency maskers. In contrast,
      recovery from a high-level (92 dB SPL) 2.4-kHz forward masker was slower than
      from the equivalent on-frequency masker. The results were used to simulate
      temporal masking curves, taking into account the differences in on- and off
      frequency masking recoveries at high levels. The predictions suggest that
      compression estimates assuming frequency-independent masking recovery may
      overestimate compression by as much as a factor of 2. The results suggest caution
      in interpreting forward-masking data in terms of basilar-membrane compression,
      particularly when high-level maskers are involved.

PMID- 19173416
TI  - The decision process in forward-masked intensity discrimination: evidence from
      molecular analyses.
AB  - In a two-interval forced-choice intensity discrimination task presenting a fixed
      increment, the level of the forward masker in interval 1 and interval 2 was
      sampled independently from the same normal distribution on each trial. Mean and
      standard deviation of the distribution were varied. Correlational analyses of the
      trial-by-trial data revealed different decision strategies depending on the
      relation between mean masker level and standard level. If the two levels were
      identical, listeners tended to select the interval containing the higher-level
      masker, behaving like an energy detector at the output of a temporal window of
      integration. For mean masker level higher than the standard level, most listeners
      showed a negative correlation between the masker level in a given interval and
      the probability of selecting this interval, indicating a strategy of comparing
      the masker loudness and the target loudness in each of the two observation
      intervals, and voting for the interval where the loudness difference was smaller.
      Implications for models of forward-masked intensity discrimination and
      differences from decision strategies reported for forward-masked detection tasks
      [Jesteadt et al., (2005). "Effect of variability in level on forward masking and
      on increment detection," J. Acoust. Soc. Am. 118, 325-337] are discussed.

PMID- 19173417
TI  - Frequency difference limens of pure tones and harmonics within complex stimuli in
      Mongolian gerbils and humans.
AB  - Frequency difference limens (FDLs) for pure tones between 200 and 6400 Hz and for
      the first, the second, or the eighth harmonic of an 800 Hz complex in four
      Mongolian gerbils (Meriones unguiculatus) were determined using a Go/NoGo
      procedure. The 12 harmonics of the complex started either in sine phase or at a
      random phase. Gerbils showed very high pure tone FDLs ranging from 17.1% Weber
      fraction (200 Hz) to 6.7% (6400 Hz). They performed much better in detecting
      mistuning of a harmonic in the complex in the sine phase condition with FDLs
      decreasing from 0.07% for the first harmonic to 0.02% for the eighth harmonic.
      FDLs were about one order of magnitude higher when temporal cues were degraded by
      randomizing the starting phase of every component in the harmonic complex for
      every stimulus. These results are strikingly different from those obtained in
      four human subjects who needed about four times higher frequency shifts than
      gerbils for detecting a mistuned component in a sine phase complex and showed
      similar detection of mistuning in the random phase condition. The results are
      discussed in relation to possible processing mechanisms for pure tone frequency
      discrimination and for detecting mistuning in harmonic complex stimuli.

PMID- 19173418
TI  - Critical bands and critical ratios in animal psychoacoustics: an example using
      chinchilla data.
AB  - This paper suggests that critical ratios obtained in noise-masked tone studies
      are not good indicators of critical bandwidths obtained in both human and
      nonhuman animal subjects. A probe-tone detection study using chinchilla subjects
      suggests that they may be broadband processors in detection tasks as opposed to
      human subjects who use narrow-band, critical-band processing. If chinchilla and
      other nonhuman animal subjects are wideband processors, this can partially
      explain why their critical ratios are significantly greater than those measured
      in human subjects. Thus, large critical ratios obtained for nonhuman animals may
      indicate processing inefficiency rather than wide critical bands.

PMID- 19173419
TI  - Pitch discrimination interference: the role of ear of entry and of octave
      similarity.
AB  - Gockel et al. [(2004). J. Acoust. Soc. Am. 116, 1092-1104] reported that
      discrimination of the fundamental frequency (F0) of two sequentially presented
      complex tones (the target) was impaired when an additional complex tone (the
      interferer) was presented simultaneously with and to the same ear as the target,
      even though the target and interferer were filtered into separate frequency
      regions. This pitch discrimination interference (PDI) was greatest when the
      target and interferer had similar F0s. The current study examined the role of
      relative ear of entry of the target and interferer and whether the dependence of
      the PDI effect on the relative F0 of target and interferer is based on pitch
      height (F0 as such) or pitch chroma (the musical note). Sensitivity (d(')) was
      measured for discrimination of the F0 of a target with a nominal F0 of 88 Hz,
      bandpass filtered from 1375 to 1875 Hz. The interferer was bandpass filtered from
      125 to 625 Hz. The contralateral interferer produced marked PDI, but smaller than
      for ipsilateral presentation. PDI was not larger when the interferer's F0 was
      twice the nominal target F0 than when it was a factor of 1.9 or 2.1 higher.

PMID- 19173420
TI  - The relationship between pitch discrimination and vocal production: comparison of
      vocal and instrumental musicians.
AB  - Auditory pitch discrimination and vocal pitch accuracy are fundamental abilities
      and essential skills of a professional singer; yet, the relationship between
      these abilities, particularly in trained vocal musicians, has not been the
      subject of much research. Difference limens for frequency (DLFs) and pitch
      production accuracy (PPA) were examined among 20 vocalists, 21 instrumentalists,
      and 21 nonmusicians. All were right-handed young adult females with normal
      hearing. Stimuli were harmonic tone complexes simulating piano tones and
      represented the mid-frequency of the untrained female vocal range, F0=261.63-392
      Hz (C4-G4). DLFs were obtained by an adaptive psychophysical paradigm. Vocal
      pitch recordings were analyzed to determine PPA. Musicians demonstrated superior
      pitch discrimination and production accuracy compared to nonmusicians. These
      abilities did not distinguish instrumentalists and vocalists. DLF and PPA were
      significantly correlated with each other only for musicians with instrumental
      training; however, PPA was most consistent with minimal variance for vocalists.
      It would appear that a relationship between DLF and PPA develops with musical
      training, and these abilities can be differentially influenced by the type of
      specialty training.

PMID- 19173421
TI  - Spectral weights for sample discrimination as a function of overall level.
AB  - Doherty and Lutfi [(1996). "Spectral weights for overall level discrimination in
      listeners with sensorineural hearing loss," J. Acoust. Soc. Am. 99, 1053-1058]
      examined the weights assigned to individual components of a six-tone complex
      during a sample discrimination task and reported that hearing-impaired subjects
      gave the most weight to components in the region of their high-frequency hearing
      loss. In contrast, weighting patterns varied for normal-hearing subjects. In the
      current study, the same six-tone complex, comprised of the octave frequencies
      from 0.25 to 8 kHz, was presented to three subjects with normal hearing in high
      pass noise, in low-pass noise, and in quiet at two overall levels. Consistent
      with Doherty and Lutfi, subjects assigned more weight to the 4-kHz component in
      the high-pass noise condition, but roughly equal weight to all components in the
      lower-level quiet condition. Weights in the low-pass noise and higher-level quiet
      conditions, however, were similar to those in the high-pass noise condition. A
      second experiment compared weights for seven subjects in quiet at four different
      mean levels. Weights for the highest-frequency components increased as the
      overall level of the complexes was increased. These results suggest that overall
      level, rather than degree of hearing loss or sensation level, was the primary
      cause of the effect that Doherty and Lutfi observed.

PMID- 19173422
TI  - Acoustic, psychophysical, and neuroimaging measurements of the effectiveness of
      active cancellation during auditory functional magnetic resonance imaging.
AB  - Functional magnetic resonance imaging (fMRI) is one of the principal neuroimaging
      techniques for studying human audition, but it generates an intense background
      sound which hinders listening performance and confounds measures of the auditory
      response. This paper reports the perceptual effects of an active noise control
      (ANC) system that operates in the electromagnetically hostile and physically
      compact neuroimaging environment to provide significant noise reduction, without
      interfering with image quality. Cancellation was first evaluated at 600 Hz,
      corresponding to the dominant peak in the power spectrum of the background sound
      and at which cancellation is maximally effective. Microphone measurements at the
      ear demonstrated 35 dB of acoustic attenuation [from 93 to 58 dB sound pressure
      level (SPL)], while masked detection thresholds improved by 20 dB (from 74 to 54
      dB SPL). Considerable perceptual benefits were also obtained across other
      frequencies, including those corresponding to dips in the spectrum of the
      background sound. Cancellation also improved the statistical detection of sound
      related cortical activation, especially for sounds presented at low intensities.
      These results confirm that ANC offers substantial benefits for fMRI research.

PMID- 19173423
TI  - Speech enhancement with multichannel Wiener filter techniques in multimicrophone
      binaural hearing aids.
AB  - This paper evaluates speech enhancement in binaural multimicrophone hearing aids
      by noise reduction algorithms based on the multichannel Wiener filter (MWF) and
      the MWF with partial noise estimate (MWF-N). Both algorithms are specifically
      developed to combine noise reduction with the preservation of binaural cues.
      Objective and perceptual evaluations were performed with different speech-in
      multitalker-babble configurations in two different acoustic environments. The
      main conclusions are as follows: (a) A bilateral MWF with perfect voice activity
      detection equals or outperforms a bilateral adaptive directional microphone in
      terms of speech enhancement while preserving the binaural cues of the speech
      component. (b) A significant gain in speech enhancement is found when
      transmitting one contralateral microphone signal to the MWF active at the
      ipsilateral hearing aid. Adding a second contralateral microphone showed a
      significant improvement during the objective evaluations but not in the subset of
      scenarios tested during the perceptual evaluations. (c) Adding the partial noise
      estimate to the MWF, done to improve the spatial awareness of the hearing aid
      user, reduces the amount of speech enhancement in a limited way. In some
      conditions the MWF-N even outperformed the MWF possibly due to an improved
      spatial release from masking.

PMID- 19173424
TI  - Speech recognition by bilateral cochlear implant users in a cocktail-party
      setting.
AB  - Unlike prior studies with bilateral cochlear implant users which considered only
      one interferer, the present study considered realistic listening situations
      wherein multiple interferers were present and in some cases originating from both
      hemifields. Speech reception thresholds were measured in bilateral users
      unilaterally and bilaterally in four different spatial configurations, with one
      and three interferers consisting of modulated noise or competing talkers. The
      data were analyzed in terms of binaural benefits including monaural advantage
      (better-ear listening) and binaural interaction. The total advantage (overall
      spatial release) received was 2-5 dB and was maintained with multiple interferers
      present. This advantage was dominated by the monaural advantage, which ranged
      from 1 to 6 dB and was largest when the interferers were mostly energetic. No
      binaural-interaction benefit was found in the present study with either type of
      interferer (speech or noise). While the total and monaural advantage obtained for
      noise interferers was comparable to that attained by normal-hearing listeners, it
      was considerably lower for speech interferers. This suggests that bilateral users
      are less capable of taking advantage of binaural cues, in particular, under
      conditions of informational masking. Furthermore, the use of noise interferers
      does not adequately reflect the difficulties experienced by bilateral users in
      real-life situations.

PMID- 19173425
TI  - Talkers alter vowel production in response to real-time formant perturbation even
      when instructed not to compensate.
AB  - Talkers show sensitivity to a range of perturbations of auditory feedback (e.g.,
      manipulation of vocal amplitude, fundamental frequency and formant frequency).
      Here, 50 subjects spoke a monosyllable ("head"), and the formants in their speech
      were shifted in real time using a custom signal processing system that provided
      feedback over headphones. First and second formants were altered so that the
      auditory feedback matched subjects' production of "had." Three different
      instructions were tested: (1) control, in which subjects were naive about the
      feedback manipulation, (2) ignore headphones, in which subjects were told that
      their voice might sound different and to ignore what they heard in the
      headphones, and (3) avoid compensation, in which subjects were informed in detail
      about the manipulation and were told not to compensate. Despite explicit
      instruction to ignore the feedback changes, subjects produced a robust
      compensation in all conditions. There were no differences in the magnitudes of
      the first or second formant changes between groups. In general, subjects altered
      their vowel formant values in a direction opposite to the perturbation, as if to
      cancel its effects. These results suggest that compensation in the face of
      formant perturbation is relatively automatic, and the response is not easily
      modified by conscious strategy.

PMID- 19173426
TI  - Low-dimensional models of the glottal flow incorporating viscous-inviscid
      interaction.
AB  - The behavior of glottal flow can, to a large extent, be characterized by
      development and separation of the boundary layer. The point of flow separation is
      known to vary during the phonatory cycle due to change in channel configuration.
      To take the movable nature of the separation point into account, the boundary
      layer equation is solved numerically, and the values of the characteristic
      quantities are determined as well as the point of separation. Development of the
      boundary layer in general reduces the effective size of the channel, and,
      therefore, increases the core flow velocity, which, in turn provides the boundary
      condition of the boundary-layer equation. The interaction between the viscous
      (boundary layer) and inviscid (core flow) parts of the glottal flow is,
      therefore, strongly indicated. To apply this viscous-inviscid interaction, the
      expression of the core flow is derived for a two-dimensional flow field, and is
      solved jointly with the boundary-layer equation. Numerical results are shown to
      examine the effect of the Reynolds number and glottal configuration, with special
      emphasis on the comparison of flow models developed for one- and two-dimensional
      flow fields. Numerical results are also quantitatively compared with data
      obtained from flow measurement experiments.

PMID- 19173427
TI  - Modeling tone and intonation in Mandarin and English as a process of target
      approximation.
AB  - This paper reports the development of a quantitative target approximation (qTA)
      model for generating F(0) contours of speech. The qTA model simulates the
      production of tone and intonation as a process of syllable-synchronized
      sequential target approximation [Xu, Y. (2005). "Speech melody as articulatorily
      implemented communicative functions," Speech Commun. 46, 220-251]. It adopts a
      set of biomechanical and linguistic assumptions about the mechanisms of speech
      production. The communicative functions directly modeled are lexical tone in
      Mandarin and lexical stress in English and focus in both languages. The qTA model
      is evaluated by extracting function-specific model parameters from natural speech
      via supervised learning (automatic analysis by synthesis) and comparing the F(0)
      contours generated with the extracted parameters to those of natural utterances
      through numerical evaluation and perceptual testing. The F(0) contours generated
      by the qTA model with the learned parameters were very close to the natural
      contours in terms of root mean square error, rate of human identification of
      tone, and focus and judgment of naturalness by human listeners. The results
      demonstrate that the qTA model is both an effective tool for research on tone and
      intonation and a potentially effective system for automatic synthesis of tone and
      intonation.

PMID- 19173428
TI  - Effects of obstruent consonants on fundamental frequency at vowel onset in
      English.
AB  - When a vowel follows an obstruent, the fundamental frequency in the first few
      tens of milliseconds of the vowel is known to be influenced by the voicing
      characteristics of the consonant. This influence was re-examined in the study
      reported here. Stops, fricatives, and the nasal /m/ were paired with the vowels
      /i,a/ to form CVm syllables. Target syllables were embedded in carrier sentences,
      and intonation was varied to produce each syllable in either a high, low, or
      neutral pitch environment. In a high-pitch environment, F0 following voiceless
      obstruents is significantly increased relative to the baseline /m/, but following
      voiced obstruents it closely traces the baseline. In a low-pitch environment, F0
      is very slightly increased following all obstruents, voiced and unvoiced. It is
      suggested that for certain pitch environments a conflict can occur between
      gestures corresponding to the segmental feature [stiff vocal folds] and
      intonational elements. The results are different acoustic manifestations of
      [stiff] in different pitch environments. The spreading of the vocal folds that
      occurs during unvoiced stops in certain contexts in English is an enhancing
      gesture, which aids the resolution of the gestural conflict by allowing the
      defining segmental gesture to be weakened without losing perceptual salience.

PMID- 19173429
TI  - The contribution of temporal fine structure to the intelligibility of speech in
      steady and modulated noise.
AB  - Speech reception thresholds were measured with steady and amplitude-modulated
      noise maskers for signals processed to contain variable amounts of temporal fine
      structure (TFS) information. Subjects benefited more from TFS information for the
      modulated than for the steady masker. For both maskers, addition of TFS
      information up to 548 Hz improved performance, though the improvement was greater
      for the modulated masker. The addition of TFS information at higher frequencies
      improved performance further for the modulated masker only. These results are
      consistent with the idea that TFS information is important for listening in the
      dips of a fluctuating masker.

PMID- 19173430
TI  - Lexical and indexical cues in masking by competing speech.
AB  - Three experiments were conducted using the TVM sentences, a new set of stimuli
      for competing speech research. These open-set sentences incorporate a cue name
      that allows the experimenter to direct the listener's attention to a target
      sentence. The first experiment compared the relative efficacy of directing the
      listener's attention to the cue name versus instructing the subject to listen for
      a particular talker's voice. Results demonstrated that listeners could use either
      cue about equally well to find the target sentence. Experiment 2 was designed to
      determine whether differences in intelligibility among talkers' voices that were
      noted when three utterances were presented together persisted when each talker's
      sentences were presented in steady-state noise. Results of experiment 2 showed
      only minor intelligibility differences between talkers' utterances presented in
      noise. The final experiment considered how providing accurate and inaccurate
      information about the target talker's voice influenced speech recognition
      performance. This voice cue was found to have minimal effect on listeners'
      ability to understand the target utterance or ignore a masking voice.

PMID- 19173432
TI  - English /r/-/l/ category assimilation by Japanese adults: individual differences
      and the link to identification accuracy.
AB  - Native speakers of Japanese often have difficulty identifying English /r/ and
      /l/, and it has been thought that second-language (L2) learning difficulties like
      this are caused by how L2 phonemes are assimilated into ones native phonological
      system. This study took an individual difference approach to examining this
      relationship by testing the category assimilation of Japanese speakers with a
      wide range of English /r/-/l/ identification abilities. All Japanese subjects
      were assessed in terms of (1) their accuracy in identifying English /r/ and /l/,
      (2) their assimilation of /r/ and /l/ into their Japanese flap category, (3)
      their production of /r/ and /l/, and (4) their best-exemplar locations for /r/,
      /l/, and Japanese flap in a five-dimensional set of synthetic stimuli (F1, F2,
      F3, closure duration, and transition duration). The results demonstrated that
      Japanese speakers assimilate /l/ into their flap category more strongly than they
      assimilate /r/. However, there was little evidence that category assimilation was
      predictive of English /r/-/l/ perception and production. Japanese speakers had
      three distinct best exemplars for /r/, /l/, and flap, and only their
      representation of F3 in /r/ and /l/ was predictive of identification ability.

PMID- 19173431
TI  - Masking release for low- and high-pass-filtered speech in the presence of noise
      and single-talker interference.
AB  - Speech intelligibility was measured for sentences presented in spectrally matched
      steady noise, single-talker interference, or speech-modulated noise. The stimuli
      were unfiltered or were low-pass (LP) (1200 Hz cutoff) or high-pass (HP) (1500 Hz
      cutoff) filtered. The cutoff frequencies were selected to produce equal
      performance in both LP and HP conditions in steady noise and to limit access to
      the temporal fine structure of resolved harmonics in the HP conditions. Masking
      release, or the improvement in performance between the steady noise and single
      talker interference, was substantial with no filtering. Under LP and HP
      filtering, masking release was roughly equal but was much less than in unfiltered
      conditions. When the average F0 of the interferer was shifted lower than that of
      the target, similar increases in masking release were observed under LP and HP
      filtering. Similar LP and HP results were also obtained for the speech-modulated
      noise masker. The findings are not consistent with the idea that pitch conveyed
      by the temporal fine structure of low-order harmonics plays a crucial role in
      masking release. Instead, any reduction in speech redundancy, or manipulation
      that increases the target-to-masker ratio necessary for intelligibility to beyond
      around 0 dB, may result in reduced masking release.

PMID- 19173433
TI  - Automatic source speaker selection for voice conversion.
AB  - This paper focuses on the importance of source speaker selection for a weighted
      codebook mapping based voice conversion algorithm. First, the dependency on
      source speakers is evaluated in a subjective listening test using 180 different
      source-target pairs from a database of 20 speakers. Subjective scores for
      similarity to target speaker's voice and quality are obtained. Statistical
      analysis of scores confirms the dependence of performance on source speakers for
      both male-to-male and female-to-female transformations. A source speaker
      selection algorithm is devised given a target speaker and a set of source speaker
      candidates. For this purpose, an artificial neural network (ANN) is trained that
      learns the regression between a set of acoustical distance measures and the
      subjective scores. The estimated scores are used in source speaker ranking. The
      average cross-correlation coefficient between rankings obtained from median
      subjective scores and rankings estimated by the algorithm is 0.84 for similarity
      and 0.78 for quality in male-to-male transformations. The results for female-to
      female transformations were less reliable with a cross-correlation value of 0.58
      for both similarity and quality.

PMID- 19173434
TI  - Detection of time-varying harmonic amplitude alterations due to spectral
      interpolations between musical instrument tones.
AB  - Gradated spectral interpolations between musical instrument tone pairs were used
      to investigate discrimination as a function of time-averaged spectral difference.
      All possible nonidentical pairs taken from a collection of eight musical
      instrument sounds consisting of bassoon, clarinet, flute, horn, oboe, saxophone,
      trumpet, and violin were tested. For each pair, several tones were generated with
      different balances between the primary and secondary instruments, where the
      balance was fixed across the duration of each tone. Among primary instruments it
      was found that changes to horn and bassoon [corrected] were most easily
      discriminable, while changes to saxophone and trumpet timbres were least
      discriminable. Among secondary instruments, the clarinet had the strongest effect
      on discrimination, whereas the bassoon had the least effect. For primary
      instruments, strong negative correlations were found between discrimination and
      their spectral incoherences, suggesting that the presence of dynamic spectral
      variations tends to increase the difficulty of detecting time-varying alterations
      such as spectral interpolation.

PMID- 19173435
TI  - Voice classification and vocal tract of singers: a study of x-ray images and
      morphology.
AB  - This investigation compares vocal tract dimensions and the classification of
      singer voices by examining an x-ray material assembled between 1959 and 1991 of
      students admitted to the solo singing education at the University of Music,
      Dresden, Germany. A total of 132 images were available to analysis. Different
      classifications' values of the lengths of the total vocal tract, the pharynx, and
      mouth cavities as well as of the relative position of the larynx, the height of
      the palatal arch, and the estimated vocal fold length were analyzed
      statistically, and some significant differences were found. The length of the
      pharynx cavity seemed particularly influential on the total vocal tract length,
      which varied systematically with classification. Also studied were the
      relationships between voice classification and the body height and weight and the
      body mass index. The data support the hypothesis that there are consistent
      morphological vocal tract differences between singers of different voice
      classifications.

PMID- 19173436
TI  - Quantifying bat call detection performance of humans and machines.
AB  - Methods for detecting echolocation calls in field recordings of bats vary in
      performance and influence the effective range of a recording system. In
      experiments using synthetic calls from five species, human detection accuracy was
      89.7+/-0.6%, compared to 76.3+/-0.8% for a model-based detector, 72.2+/-0.8% for
      an energy-based detector, and 98.4+/-0.2% for an optimal linear detector. The
      energy-based detector was 11 times faster than the model-based detector and 110
      times faster than humans. Human accuracy was positively correlated with test
      duration (R(2)=0.43, P<0.05), meaning that higher accuracy was achieved at the
      expense of slower performance. Species was a significant factor determining
      accuracy for all detectors (P<0.001) because of call bandwidth: Narrowband calls
      concentrated energy in a narrower frequency band and were easier to detect. For a
      hypothetical recording system, range at 90% human detection accuracy varied from
      10 to 35 m among species, while range dropped by approximately 20% using the
      automated detectors. The optimal detector outperformed humans by 5 dB and the
      automated methods by 9 dB. The results quantify the tradeoff between detector
      speed and accuracy and are useful for designing field studies of bats.

PMID- 19173437
TI  - Bone sonometry: reducing phase aberration to improve estimates of broadband
      ultrasonic attenuation.
AB  - Previous studies suggest that phase cancellation at the receiving transducer can
      result in the overestimation of the frequency dependent ultrasonic attenuation of
      bone, a quantity that has been shown to correlate with bone mineral density and
      ultimately with osteoporotic fracture risk. Evidence supporting this
      interpretation is provided by phase insensitive processing of the data, which
      appear to reduce the apparent overestimates of attenuation. The present study was
      designed to clarify the components underlying phase aberration artifacts in such
      through-transmission measurements by conducting systematic studies of the
      simplest possible test objects capable of introducing phase aberration.
      Experimental results are presented for a Lexan phantom over the frequency range
      300-700 kHz and a Plexiglas phantom over the 3-7 MHz range. Both phantoms were
      flat and parallel plates featuring a step discontinuity milled into one of their
      initially flat sides. The through-transmitted signals were received by a 0.6 mm
      diameter membrane hydrophone that was raster scanned over a grid coaxial with the
      transmitting transducer. Signals received by the pseudoarray were processed
      offline to emulate phase sensitive and phase insensitive receivers with different
      aperture diameters. The data processed phase sensitively were focused to
      demonstrate the results of planar, geometrical, and correlation-based aberration
      correction methods. Results are presented illustrating the relative roles of
      interference in the ultrasonic field and phase cancellation at the receiving
      transducer in producing phase aberration artifacts. It was found that artifacts
      due to phase cancellation or interference can only be minimized with phase
      insensitive summation techniques by choosing an appropriately large receiving
      aperture. Data also suggest the potentially confounding role of time-and
      frequency-domain artifacts on ultrasonic measurements and illustrate the
      advantages of two-dimensional receiving arrays in determining the slope of
      attenuation (nBUA) for the clinical assessment of osteoporosis.

PMID- 19173438
TI  - Interest of the attenuation coefficient in multiparametric high frequency
      ultrasound investigation of whole blood coagulation process.
AB  - Previous studies [R. Libgot, F. Ossant, Y. Gruel, P. Lermusiaux, and F. Patat,
      Proc.-IEEE Utrason. Symp. 4, 2259-2262 (2005); R. Libgot-Calle, F. Ossant, Y.
      Gruel, P. Lermusiaux, and F. Patat, Ultrasound Med. Biol. 34, 252-264 (2008); F.
      Ossant, R. Libgot, P. Coupe, P. Lermusiaux, and F. Patat, Proc.-IEEE Ultrason.
      Symp. 2, 846-849 (2004)] showed the potential of an in vitro high frequency
      ultrasound (beyond 20 MHz) device to describe the blood clotting process. The
      parameters were simultaneously estimated in double transmission (DT) with the
      calculation of the velocity of longitudinal waves and in backscattering (BS)
      modes with the estimation of the integrated BS coefficient and the effective
      scatterer size. The aim of the present study was to show how the integrated
      attenuation coefficient (IAC) assessed in DT mode could provide additional
      information on this process, especially regarding the fibrin polymerization which
      is an important part of the coagulation process. A characteristic time t(a) of
      the variations in IAC that could be linked to fibrin formation was identified.

PMID- 19173439
TI  - Phonation behavior of cooperatively foraging spinner dolphins.
AB  - Groups of spinner dolphins have been shown to cooperatively herd small prey. It
      was hypothesized that the strong group coordination is maintained by acoustic
      communication, specifically by frequency-modulated whistles. Observations of
      groups of spinner dolphins foraging at night within a sound-scattering layer were
      made with a multibeam echosounder while the rates of dolphin sounds were measured
      using four hydrophones at 6 m depth intervals. Whistles were only detected when
      dolphins were not foraging and when animals were surfacing. Differences in click
      rates were found between depths and between different foraging stages but were
      relatively low when observations indicated that dolphins were actively feeding
      despite the consistency of these clicks with echolocation signals. Highest click
      rates occurred within the scattering layer, during transitions between foraging
      states. This suggests that clicks may be used directly or indirectly to cue group
      movement during foraging, potentially by detecting other individuals' positions
      in the group or serving a direct communicative role which would be contrary to
      the existing assumption that echolocation and communication are
      compartmentalized. Communicating via clicks would be beneficial as the signal's
      characteristics minimize the chance of eavesdropping by competing dolphins and
      large fish. Our results are unable to support the established paradigm for
      dolphin acoustic communication and suggest an alternate coordination mechanism in
      foraging spinner dolphins.

PMID- 19173440
TI  - Comparison of stationary acoustic monitoring and visual observation of finless
      porpoises.
AB  - The detection performance regarding stationary acoustic monitoring of Yangtze
      finless porpoises Neophocaena phocaenoides asiaeorientalis was compared to visual
      observations. Three stereo acoustic data loggers (A-tag) were placed at different
      locations near the confluence of Poyang Lake and the Yangtze River, China. The
      presence and number of porpoises were determined acoustically and visually during
      each 1-min time bin. On average, porpoises were acoustically detected 81.7+/-9.7%
      of the entire effective observation time, while the presence of animals was
      confirmed visually 12.7+/-11.0% of the entire time. Acoustic monitoring indicated
      areas of high and low porpoise densities that were consistent with visual
      observations. The direction of porpoise movement was monitored using stereo
      beams, which agreed with visual observations at all monitoring locations.
      Acoustic and visual methods could determine group sizes up to five and ten
      individuals, respectively. While the acoustic monitoring method had the advantage
      of high detection probability, it tended to underestimate group size due to the
      limited resolution of sound source bearing angles. The stationary acoustic
      monitoring method proved to be a practical and useful alternative to visual
      observations, especially in areas of low porpoise density for long-term
      monitoring.

PMID- 19173441
TI  - Behavioral responses of herring (Clupea harengus) to 1-2 and 6-7 kHz sonar
      signals and killer whale feeding sounds.
AB  - Military antisubmarine sonars produce intense sounds within the hearing range of
      most clupeid fish. The behavioral reactions of overwintering herring (Clupea
      harengus) to sonar signals of two different frequency ranges (1-2 and 6-7 kHz),
      and to playback of killer whale feeding sounds, were tested in controlled
      exposure experiments in Vestfjorden, Norway, November 2006. The behavior of free
      ranging herring was monitored by two upward-looking echosounders. A vessel towing
      an operational naval sonar source approached and passed over one of them in a
      block design setup. No significant escape reactions, either vertically or
      horizontally, were detected in response to sonar transmissions. Killer whale
      feeding sounds induced vertical and horizontal movements of herring. The results
      indicate that neither transmission of 1-2 kHz nor 6-7 kHz have significant
      negative influence on herring on the received sound pressure level tested (127
      197 and 139-209 dB(rms) re 1 microPa, respectively). Military sonars of such
      frequencies and source levels may thus be operated in areas of overwintering
      herring without substantially affecting herring behavior or herring fishery. The
      avoidance during playback of killer whale sounds demonstrates the nature of an
      avoidance reaction and the ability of the experimental design to reveal it.

PMID- 19173501
TI  - Dissociative recombination of highly enriched para-H3+.
AB  - The determination of the dissociative recombination rate coefficient of H(3) (+)
      has had a turbulent history, but both experiment and theory have recently
      converged to a common value. Despite this convergence, it has not been clear if
      there should be a difference between the rate coefficients for ortho-H(3) (+) and
      para-H(3) (+). A difference has been predicted theoretically and could
      conceivably impact the ortho:para ratio of H(3) (+) in the diffuse interstellar
      medium, where H(3) (+) has been widely observed. We present the results of an
      experiment at the CRYRING ion storage ring in which we investigated the
      dissociative recombination of highly enriched ( approximately 83.6%) para-H(3)
      (+) using a supersonic expansion source that produced ions with T(rot)
      approximately 60-100 K. We observed an increase in the low energy recombination
      rate coefficient of the enriched para-H(3) (+) by a factor of approximately 1.25
      in comparison to H(3) (+) produced from normal H(2) (ortho:para=3:1). The ratio
      of the rate coefficients of pure para-H(3) (+) to that of pure ortho-H(3) (+) is
      inferred to be approximately 2 at low collision energies; the corresponding ratio
      of the thermal rate coefficients is approximately 1.5 at electron temperatures
      from 60 to 1000 K. We conclude that this difference is unlikely to have an impact
      on the interstellar ortho:para ratio of H(3) (+).

PMID- 19173502
TI  - Vibrationally inelastic collisions of H+D2: a comparison of quantum mechanical,
      quasiclassical, and experimental results.
AB  - A detailed comparison of quantum mechanical (QM) and quasiclassical trajectory
      (QCT) integral and differential cross sections (DCSs) as well as opacity
      functions is presented in this work for the vibrationally inelastic collisions of
      H+D(2)(v=0,j=0)-->H+D(2)(v(')=3,j(')) at 1.72 eV collision energy. These results
      are also compared with the experimental differential cross sections by Greaves et
      al. [Nature (London) 454, 88 (2008)]. The agreement between QCT and QM results is
      fairly good but some differences are appreciable, and it is shown that the
      experimental results are in a somewhat better agreement with the calculated QM
      DCS. The present results and their analysis confirm that the vibrational
      excitation takes place by elongation of the D-D bond in a "tug-of-war" mechanism,
      where the incoming H atom and one of the D atoms compete for the formation of a
      bond with the other D atom, as proposed by Greaves et al. It is also found that
      these collisions may give rise to the formation of short-lived collision
      complexes (tau(coll)=35-50 fs) that can be traced back to the presence of
      relatively deep wells in the potential surface when the original D-D bond is
      stretched. The analysis of the trajectories into v(')=3 reveals that most of them
      cross at least twice the reaction barrier via a recrossing mechanism.

PMID- 19173503
TI  - Solid-solid transition of the size-polydisperse hard sphere system.
AB  - The solid-solid coexistence of a polydisperse hard sphere system is studied by
      using the Monte Carlo simulation. The results show that for large enough
      polydispersity the solid-solid coexistence state is more stable than the single
      phase solid. The two coexisting solids have different composition distributions
      but the same crystal structure. Moreover, there is evidence that the solid-solid
      transition terminates in a critical point as in the case of the fluid-fluid
      transition.

PMID- 19173504
TI  - Kinetic energy density study of confined noninteracting fermions: the importance
      of the angular momentum.
AB  - In this work we present a study of the kinetic energy density of an arbitrary
      number of noninteracting fermions confined in a Coulombic potential. We present
      the results for the total kinetic energy and the kinetic energy density using
      three simple but representative functionals: Thomas-Fermi, von Weizsaker, and the
      second order gradient expansion approximation. In order to assess their quality,
      the deviation of the kinetic energy density of every functional is measured
      through a parameter that reflects the quality of the functionals in a better way
      than their relative errors (for that reason, we call it quality factor). Trying
      to understand the performance of the different functionals we study degenerate
      states with the same energy but different angular momenta and densities.
      Therefore, the functionals' ability to capture the effects of each density
      corresponding to the different angular momenta is discussed, as well as the
      trends of these contributions.

PMID- 19173505
TI  - Theoretical description of charge migration with a single Slater-determinant and
      beyond.
AB  - Triggered by the interest to study charge migration in large molecular systems, a
      simple methodology has recently been proposed based on straightforward density
      functional theory calculations. This approach describes the time evolution of the
      initially created hole density in terms of the time evolution of the ionized
      highest occupied molecular orbital (HOMO). Here we demonstrate that this time
      dependent analog of Koopmans' theorem is not valid, and instead of the time
      evolution of the HOMO, the time evolution of the orbitals that remain occupied in
      the cation determines the evolution of the initially created hole in the
      framework of time-dependent single-determinant theories. Numerical examples
      underline that for a proper description of charge migration processes, an
      explicit treatment of the electron correlation is indispensable. Moreover, they
      also demonstrate that the attempts to describe charge migration based on Kohn
      Sham density functional theory using conventional exchange-correlation
      functionals are doomed to fail due to the well-known self-interaction error.

PMID- 19173506
TI  - Third-order dispersion energy from response functions.
AB  - In the second order of perturbation theory, the dispersion component of the
      interaction energy of two atoms or molecules can be expressed as an integral of
      frequency-dependent response functions of monomers. An analogous formula is
      derived here for the third-order dispersion energies. The general formula
      involves a nonstandard response function, but for atoms in asymptotic expansion
      the expression involves only the standard dynamic hyperpolarizabilities.

PMID- 19173507
TI  - High-accuracy calculations of the ground, 1 1A1', and the 2 1A1', 2 3A1', and 1
      1E' excited states of H3+.
AB  - Accurate variational Born-Oppenheimer calculations of the 1 (1)A(1) ('), 2
      (1)A(1) ('), 2 (3)A(1) ('), and 1 (1)E(') states of the H(3) (+) ion at the
      ground-state equilibrium geometry are reported. The wave functions of the states
      are expanded in terms of explicitly correlated spherical Gaussian functions with
      shifted centers. In the variational optimization the analytical gradient of the
      energy with respect to the nonlinear exponential parameters of the Gaussians has
      been employed. The energies obtained in the calculations are the best variational
      estimates ever calculated for the four states. One-electron densities for the
      states, as well as a D(3h)-restricted potential energy surface of the ground
      state calculated around the equilibrium geometry, are also presented and
      discussed.

PMID- 19173508
TI  - A finite-difference implementation of the Caldeira-Leggett master equation.
AB  - The Caldeira-Leggett master equation for dissipative quantum dynamics has
      predominantly been implemented in phase space, where it plays the role of a
      quantum Fokker-Planck equation. Here we demonstrate the feasibility of a pure
      coordinate space implementation in the case of intermediate damping strength and
      temperature, for times long enough to observe thermal equilibration. After a
      thorough numerical investigation of the analytically solvable harmonic oscillator
      case, a Morse oscillator model is studied. This is a case in which a quantal
      phase space approach would be difficult to implement and we show how analytical
      results for thermal averages are reproduced to a surprisingly high degree.

PMID- 19173509
TI  - Multidimensional Langevin modeling of biomolecular dynamics.
AB  - A systematic computational approach to describe the conformational dynamics of
      biomolecules in reduced dimensionality is presented. The method is based on (i)
      the decomposition of a high-dimensional molecular dynamics trajectory into a few
      "system" and (many) "bath" degrees of freedom and (ii) a Langevin simulation of
      the resulting model. Employing principal component analysis, the dimension of the
      system is chosen such that it contains all slow large-amplitude motions of the
      molecule, while the bath coordinates only account for its high-frequency
      fluctuations. It is shown that a sufficiently large dimension of the model is
      essential to ensure a clear time scale separation of system and bath variables,
      which warrants the validity of the memory-free Langevin equation. Applying
      methods from nonlinear time series analysis, a practical Langevin algorithm is
      presented which performs a local estimation of the multidimensional Langevin
      vector fields describing deterministic drift and stochastic driving. Adopting a
      800 ns molecular dynamics simulation of the folding of heptaalanine in explicit
      water, it is shown that a five-dimensional Langevin model correctly reproduces
      the structure and conformational dynamics of the system. The virtues and limits
      of the approach are discussed in some detail.

PMID- 19173510
TI  - Condition on the Kohn-Sham kinetic energy and modern parametrization of the
      Thomas-Fermi density.
AB  - We study the asymptotic expansion of the neutral-atom energy as the atomic number
      Z-->infinity, presenting a new method to extract the coefficients from
      oscillating numerical data. Recovery of the correct expansion yields a condition
      on the Kohn-Sham kinetic energy that is important for the accuracy of approximate
      kinetic energy functionals for atoms, molecules, and solids. For example, this
      determines the small gradient limit of any generalized gradient approximation and
      conflicts somewhat with the standard gradient expansion. Tests are performed on
      atoms, molecules, and jellium clusters using densities constructed from Kohn-Sham
      orbitals. We also give a modern, highly accurate parametrization of the Thomas
      Fermi density of neutral atoms.

PMID- 19173511
TI  - Free-time and fixed end-point optimal control theory in quantum mechanics:
      application to entanglement generation.
AB  - We have constructed free-time and fixed end-point optimal control theory for
      quantum systems and applied it to entanglement generation between rotational
      modes of two polar molecules coupled by dipole-dipole interaction. The motivation
      of the present work is to solve optimal control problems more flexibly by
      extending the popular fixed time and fixed end-point optimal control theory for
      quantum systems to free-time and fixed end-point optimal control theory. As a
      demonstration, the theory that we have constructed in this paper will be applied
      to entanglement generation in rotational modes of NaCl-NaBr polar molecular
      systems that are sensitive to the strength of entangling interactions. Our method
      will significantly be useful for the quantum control of nonlocal interaction such
      as entangling interaction, which depends crucially on the strength of the
      interaction or the distance between the two molecules, and other general quantum
      dynamics, chemical reactions, and so on.

PMID- 19173512
TI  - Constrained density functional theory based configuration interaction improves
      the prediction of reaction barrier heights.
AB  - In this work, a constrained density functional theory based configuration
      interaction approach (CDFT-CI) is applied to calculating transition state
      energies of chemical reactions that involve bond forming and breaking at the same
      time. At a given point along the reaction path, the configuration space is
      spanned by two diabaticlike configurations: reactant and product. Each
      configuration is constructed self-consistently with spin and charge constraints
      to maximally retain the identities of the reactants or the products. Finally, the
      total energy is obtained by diagonalizing an effective Hamiltonian constructed in
      the basis spanned by these two configurations. By design, this prescription does
      not affect the energies of the reactant or product species but will affect the
      energy at intermediate points along the reaction coordinate, most notably by
      modifying the reaction barrier height. When tested with a large set of reactions
      that include hydrogen transfer, heavy atom transfer, and nucleophilic
      substitution, CDFT-CI is found to improve the prediction of barrier heights by a
      factor of 2-3 for some commonly used local, semilocal, and hybrid functionals.
      Thus, just as CDFT can be used to cure energy errors in charge localized states,
      CDFT-CI can recover the correct energy for charge delocalized states by
      approximating the true wave function as a linear combination of localized
      configurations (e.g., reactant and product). The well-defined procedure and the
      promising results of CDFT-CI suggest that it could broaden the applicability of
      traditional DFT methods for reaction barrier heights.

PMID- 19173513
TI  - Additive and nonadditive models of vapor-liquid equilibrium in CO2 from first
      principles.
AB  - We describe quantum-chemical calculations on dimers of CO(2) and use the results
      to develop first-principles models for Gibbs ensemble Monte Carlo simulations of
      the phase coexistence curve. Isotropic pairwise potentials are insufficient to
      model the phase behavior and overestimate the binding in liquid CO(2) by 4 kJ
      mol(-1). An anisotropic treatment of the atoms in the pairwise potential reduces
      the strength of the binding by approximately 0.5 kJ mol(-1). We use ab initio
      calculations on trimers of CO(2) to assess the strength of nonadditive
      interactions. Including nonadditive dispersion in Gibbs ensemble simulations
      gives an enthalpy of vaporization within 1.5 kJ mol(-1) of the experimental value
      over a wide range of temperatures.

PMID- 19173514
TI  - Non-Condon nature of fluctuating bridges on nonadiabatic electron transfer:
      analytical interpretation.
AB  - Rigorous expressions for the calculation of nonadiabatic electron transfer rates
      are presented in closed forms for donor-acceptor systems incorporated fluctuating
      bridges and their non-Condon electronic couplings. In high temperature limit,
      they show a similar property to the Marcus formula. However, the Marcus parabolic
      with respect to the driving force is shifted for the exponential coupling while
      it becomes an overlap of several Gaussian functions for the linear coupling.
      Furthermore, the effective couplings are exponentially and linearly dependent on
      temperature and the squared frequencies of bridge modes for the exponential and
      linear couplings, respectively.

PMID- 19173515
TI  - Competition between pi and sigma hydrogen bonds and conformational probing of 2
      orthofluorophenylethanol by low-and high-resolution electronic spectroscopy.
AB  - The flexible model molecule 2-orthofluorophenylethanol has been investigated by
      laser-induced fluorescence, and low- and high-resolution resonance-enhanced two
      photon ionization spectroscopy in combination with high-level ab initio quantum
      chemistry calculations. One dominant conformation has been identified in the cold
      molecular beam corresponding to the most stable theoretically predicted gauche
      structure stabilized by an intramolecular OH...pi hydrogen bond. A tentative
      assignment of a higher-lying gauche conformer present in the molecular beam
      separated by high potential barriers from the most stable one has been made. The
      missing other higher-energy theoretically predicted conformations most likely
      relax to the most stable ones during the process of the adiabatic expansion. The
      good agreement between the experimental and theoretical results demonstrates that
      even in the case of a substitution with an electronegative atom at the ortho
      position, bringing about a significant redistribution of the electron density in
      the benzene ring and providing a convenient binding site for the formation of a
      competing OH...F sigma hydrogen bond, the nonclassical OH...pi bond remains the
      preferred binding motif for the most stable conformer.

PMID- 19173516
TI  - Space-time coupling in femtosecond pulse shaping and its effects on coherent
      control.
AB  - We present a Fourier optical analysis of a typical femtosecond pulse shaping
      apparatus and derive analytic expressions for the space-time dependence of the
      emerging waveform after the pulse shaper and in the focal volume of an additional
      focusing element. For both geometries the results are verified experimentally.
      Hereafter, we analyze the influence of space-time coupling on nonlinear
      processes, specifically second harmonic generation, resonant interaction with an
      atomic three-level system, and resonant excitation of a diatomic molecule.

PMID- 19173517
TI  - Adiabatic and nonadiabatic dissociation of ethyl radical.
AB  - Direct ab initio molecular dynamics using the trajectory surface hopping method
      with Tully's fewest switches simulates the photodissociation dynamics of ethyl
      radical, C(2)H(5), following electronic excitation to the A-state. Nonadiabatic
      dissociation dominates and produces ground state ethylene and fast hydrogen atoms
      with an anisotropic angular distribution. Surface hopping also generates hot
      ground state ethyl radicals followed ultimately by unimolecular dissociation to
      C(2)H(4)+H. The calculated excited state lifetime and the product recoil energy
      distribution obtained from an ensemble of trajectories are consistent with
      previous experiments and suggest that a strictly nonadiabatic mechanism can
      account for nonradiative decay. This process is in competition with adiabatic
      dissociation producing electronically excited state ethylene and H, a
      dissociation channel that has not yet been experimentally observed. The branching
      ratio between adiabatic and nonadiabatic dissociation pathways depends
      sensitively on the quality of the potential energy surfaces. At the
      multireference configuration interaction with singles and doubles level of
      theory, 15% of all trajectories dissociate adiabatically.

PMID- 19173518
TI  - UV photodissociation of methyl bromide and methyl bromide cation studied by
      velocity map imaging.
AB  - We employ the velocity map imaging technique to measure kinetic energy and
      angular distributions of state selected CH(3) (v(2)=0,1,2,3) and Br ((2)P(3/2),
      (2)P(1/2)) photofragments produced by methyl bromide photolysis at 215.9 nm.
      These results show unambiguously that the Br and Br( *) forming channels result
      in different vibrational excitations of the umbrella mode of the methyl fragment.
      Low energy structured features appear on the images, which arise from CH(3)Br(+)
      photodissociation near 330 nm. The excess energy of the probe laser photon is
      channeled into CH(3) (+) vibrational excitation, most probably in the nu(4)
      degenerate bend.

PMID- 19173519
TI  - UV excitation and radiationless deactivation of imidazole.
AB  - The vertical spectrum and the radiationless decay of imidazole have been
      investigated theoretically. Benchmark calculations were performed employing
      different methods and levels. Four different conical intersections were
      characterized and the reaction paths connecting the Franck-Condon region to them
      were computed. Two of the conical intersections show puckered structures while
      the other two show NH and ring dissociation patterns. The pipi( *)/S(0) N(1)
      puckered conical intersection is connected to the planar pisigma( *)/S(0) ring
      opened conical intersection by a branch of the crossing seam. After excitation
      into the first (1)pipi( *) state, the internal conversion can occur either in
      this branch of crossing seam or along the NH-dissociation path.

PMID- 19173520
TI  - Nature of Ar bonding to small Co(n+) clusters and its effect on the structure
      determination by far-infrared absorption spectroscopy.
AB  - Far-infrared vibrational spectroscopy by multiple photon dissociation has proven
      to be a very useful technique for the structural fingerprinting of small metal
      clusters. Contrary to previous studies on cationic V, Nb, and Ta clusters,
      measured vibrational spectra of small cationic cobalt clusters show a strong
      dependence on the number of adsorbed Ar probe atoms, which increases with
      decreasing cluster size. Focusing on the series Co(4) (+) to Co(8) (+) we
      therefore use density-functional theory to analyze the nature of the Ar-Co(n) (+)
      bond and its role for the vibrational spectra. In a first step, energetically low
      lying isomer structures are identified through first-principles basin-hopping
      sampling runs and their vibrational spectra are computed for a varying number of
      adsorbed Ar atoms. A comparison of these fingerprints with the experimental data
      enables in some cases a unique assignment of the cluster structure. Independent
      of the specific low-lying isomer, we obtain a pronounced increase in the Ar
      binding energy for the smallest cluster sizes, which correlates nicely with the
      observed increased influence of the Ar probe atoms on the IR spectra. Further
      analysis of the electronic structure motivates a simple electrostatic picture
      that not only explains this binding energy trend but also rationalizes the
      stronger influence of the rare-gas atom compared to the preceding studies by the
      small atomic radius of Co.

PMID- 19173521
TI  - Photodissociation dynamics of the A 2Sigma+ state of SH and SD radicals.
AB  - Atomic sulfur products from predissociation of the lowest rotational states of
      SH/SD A (2)Sigma(+) (v(')=0,1,2) are studied using velocity map imaging. The
      dissociation process, which is slow compared to rotation, is dominated by
      interference effects due to predissociation of states with low rotation quantum
      numbers prepared by photoexcitation using overlapping transitions of different
      parities. The measured product angular distributions can be modeled using the
      methods presented recently by Kim et al. [J. Chem. Phys. 125, 133316 (2006)]. The
      S((3)P(J)) (2+1) resonance enhanced multiphoton ionization scheme used in the
      detection step of the experiment is sensitive to the angular momentum
      polarization of the atomic fragments. S((3)P(J)), J=2,1,0, fine-structure yields,
      angular distributions, and atom polarization parameters are reported. Strong
      polarization of the S((3)P(2,1)) products was observed along with a weak
      sensitivity of the branching ratio to excess energy and a full insensitivity of
      the atomic product polarization to excess energy. None of the data fit the
      predictions of either adiabatic or diabatic photodissociation, emphasizing the
      need for a fully quantum treatment.

PMID- 19173522
TI  - Rotationally resolved photoelectron spectroscopic study of the Jahn-Teller effect
      in allene.
AB  - The pulsed-field-ionization zero-kinetic-energy photoelectron spectra of allene
      (C(3)H(4)) and perdeuterated allene have been recorded from the first adiabatic
      ionization energy up to 2200 cm(-1) of internal energy in the cations at a
      resolution sufficient to observe the full rotational structure. The intensity
      distributions in the spectra are dominated by vibrational progressions in the
      torsional mode, which were analyzed in the realm of a two-dimensional model of
      the Emultiply sign in circle(b(1) plus sign in circleb(2)) Jahn-Teller effect in
      the allene cation [C. Woywod and W. Domcke, Chem. Phys. 162, 349 (1992)]. Whereas
      the rotational structure of the transitions to the lowest torsional levels (0(0)
      and 4(1)) are regular and can be qualitatively analyzed in terms of a simple
      orbital ionization model, the rotational structure of the spectra of the 4(2) and
      4(3) levels are strongly perturbed. The photoelectron spectrum of C(3)H(4) also
      reveals several weak vibrational bands in the immediate vicinity of these levels
      that are indicative of (ro)vibronic perturbations. A slight broadening of the
      transitions to the 4(1) levels compared to that of the vibronic ground state and
      the increase of the number of sharp features in the rotational structure of the
      spectrum of the 4(2) level point at the importance of large-amplitude motions not
      considered in previous treatments of the Jahn-Teller effect in the allene cation.

PMID- 19173523
TI  - Fourier transform microwave spectroscopy of HZnCN(X 1Sigma+) and ZnCN(X 2Sigma+).
AB  - The pure rotational spectrum of HZnCN in its X (1)Sigma(+) electronic state has
      been recorded using pulsed Fourier transform microwave (FTMW) techniques in the
      frequency range 7-39 GHz-the first spectroscopic study of this species in the gas
      phase. The FTMW spectrum of ZnCN(X (2)Sigma(+)) has been measured as well. A new
      FTMW spectrometer with an angled beam and simplified electronics, based on a
      cryopump, was employed for these experiments. The molecules were created in a dc
      discharge from a gas mixture of Zn(CH(3))(2) and cyanogen (1% D(2) for the
      deuterated analogs), diluted with argon, that was expanded supersonically from a
      pulsed nozzle. Seven isotopologues of HZnCN arising from zinc, deuterium, and
      (13)C substitutions were studied; for every species, between three and five
      rotational transitions were recorded, each consisting of numerous hyperfine
      components arising from nitrogen, and in certain cases, deuterium, and 67-zinc
      nuclear spins. Four transitions of ZnCN were measured. From these data,
      rotational, nuclear spin-rotation, and quadrupole coupling constants have been
      determined for HZnCN, as well as rotational, and magnetic and quadrupole
      hyperfine parameters for the ZnCN radical. The bond lengths determined for HZnCN
      are r(H-Zn)=1.495 A, r(Zn-C)=1.897 A, and r(C-N)=1.146 A, while those for ZnCN
      are r(Zn-C)=1.950 A and r(C-N)=1.142 A. The zinc-carbon bond length thus shortens
      with the addition of the H atom. The nitrogen quadrupole coupling constant eqQ
      was found to be virtually identical in both cyanide species (-5.089 and -4.931
      MHz), suggesting that the electric field gradient across the N nucleus is not
      influenced by the H atom. The quadrupole constant for the (67)Zn nucleus in
      H(67)ZnCN is unusually large relative to that in (67)ZnF (-104.578 versus -60
      MHz), evidence that the bonding in the cyanide has more covalent character than
      in the fluoride. This study additionally suggests that hydrides of other metal
      cyanide species are likely candidates for high resolution spectroscopic
      investigations.

PMID- 19173524
TI  - On the importance of vibrational contributions to small-angle optical rotation:
      Fluoro-oxirane in gas phase and solution.
AB  - The specific optical rotation of (S)-fluoro-oxirane in gas phase and solution is
      predicted using time-dependent density functional theory (B3LYP functional) and
      coupled cluster linear response theory. Upon vibrational averaging, the coupled
      cluster singles and doubles model predicts the gas phase specific optical
      rotation to be 8.1 degrees (dm g/cm(3))(-1) at 355 nm at room temperature. This
      is an order of magnitude smaller than the B3LYP result of 68.4 degrees (dm
      g/cm(3))(-1). The main source of this discrepancy is the electronic contribution
      at the equilibrium geometry. The effects of cyclohexane and acetonitrile solvents
      are calculated for both the electronic and vibrational contributions with the
      B3LYP functional. The specific optical rotation is estimated to change
      significantly depending on the polarity of the solvent, increasing in cyclohexane
      and decreasing in acetonitrile.

PMID- 19173525
TI  - Structural changes of water in a hydrogel during dehydration.
AB  - Raman spectra of poly-N,N,-dimethylacrylamide hydrogel were measured in order to
      investigate the mechanism of the structural changes in water and the polymer
      network during dehydration. The results show that the vibrational energies of the
      C=O and the O-H stretching modes increase with the extent of dehydration, whereas
      that of the CH(3) rocking mode decreases. The energy shifts observed in the C=O
      stretching and CH(3) rocking modes indicate that the polymer network shrinks with
      the dehydration and undergoes a glass transition at some point. The energy shifts
      of the O-H stretching modes are attributed to changes in the water structure with
      the structural change of the polymer network. By applying a structural model of
      bulk water to the spectra of the O-H stretching region, the local water
      structures in the gel and the dried glassy polymer were analyzed. The result
      shows that a tetragonal water structure consisting of four hydrogen bonds
      increases in the residual water of the dried glassy polymer, suggesting that the
      residual water forms a two-dimensional hydrogen-bonded network. The local water
      structure in a polymer might have important implications for the interpretation
      of properties of localized water, for instance, water in a mineral crack.

PMID- 19173526
TI  - Shear induced structural ordering of a model metallic glass.
AB  - We report results of nonequilibrium molecular dynamics simulations of a one
      component glassy system under the influence of a shear flow, with the aim of
      investigating shear-induced ordering of this system. In spite of the very low
      temperature, the system transforms into a strained crystalline state through well
      defined nucleation events. Various characteristics of the observed ordering at
      different strain rates and temperatures are discussed. We also define and discuss
      the transition rates.

PMID- 19173527
TI  - Calorimetric and dielectric study of organic ferroelectrics, phenazine
      chloranilic acid, and its bromo analog.
AB  - The heat capacities of single crystals of organic ferroelectric complexes
      phenazine-chloranilic acid (Phz-H(2)ca) and phenazine-bromanilic acid (Phz
      H(2)ba) were measured. At temperatures below those of the reported ferroelectric
      phase transitions, heat capacity anomalies due to successive phase transitions
      were found in both complexes. Excess entropies involved in the low-temperature
      successive phase transitions are much larger than those due to the ferroelectric
      phase transitions. The temperature dependence of the complex dielectric constants
      showed the existence of multiple dielectric relaxation modes in both complexes
      and their deuterated analogs (Phz-D(2)ca and Phz-D(2)ba). We discuss the
      possibility of concerted hopping of neighboring protons within a hydrogen-bonded
      chain while taking into account the one-dimensional nature of the chain.

PMID- 19173528
TI  - On the interactions between molecules in an off-resonant laser beam: Evaluating
      the response to energy migration and optically induced pair forces.
AB  - Electronically excited molecules interact with their neighbors differently from
      their ground-state counterparts. Any migration of the excitation between
      molecules can modify intermolecular forces, reflecting changes to a local
      potential energy landscape. It emerges that throughput off-resonant radiation can
      also produce significant additional effects. The context for the present analysis
      of the mechanisms is a range of chemical and physical processes that
      fundamentally depend on intermolecular interactions resulting from second and
      fourth-order electric-dipole couplings. The most familiar are static dipole
      dipole interactions, resonance energy transfer (both second-order interactions),
      and dispersion forces (fourth order). For neighboring molecules subjected to off
      resonant light, additional forms of intermolecular interaction arise in the
      fourth order, including radiation-induced energy transfer and optical binding.
      Here, in a quantum electrodynamical formulation, these phenomena are cast in a
      unified description that establishes their inter-relationship and connectivity at
      a fundamental level. Theory is then developed for systems in which the interplay
      of these forms of interaction can be readily identified and analyzed in terms of
      dynamical behavior. The results are potentially significant in Forster
      measurements of conformational change and in the operation of
      microelectromechanical and nanoelectromechanical devices.

PMID- 19173529
TI  - Mode-selective vibrational redistribution after spectrally selective N-H
      stretching mode excitation in intermolecular hydrogen bonds.
AB  - Mode-selective vibrational redistribution after spectrally selective excitation
      within the highly structured N-H stretching band of the 7-azaindole dimer was
      observed by subpicosecond infrared-pump/anti-Stokes Raman-probe spectroscopy.
      Measurements after relaxation of the N-H stretching vibration indicate ultrafast
      initial population transfer to vibrations with pronounced N-H bending character.
      From these modes energy is transferred to modes of frequencies below 1000 cm(-1)
      on a slower time scale of about 3 ps. Tuning the spectrally narrow infrared
      excitation to the different substructures of the N-H stretching band influences
      the distribution of populations between the fingerprint modes. Their relative
      populations are correlated with the contributions of the modes forming the
      different coupled combination tones of the N-H stretching band. These results
      provide experimental support to a Fermi resonance model previously used for
      simulations of the N-H stretching infrared absorption band shape and insight into
      relaxation from the initially excited combination bands.

PMID- 19173530
TI  - Charge localization in alcohol isomers studied by Compton scattering.
AB  - The isomers of small molecule alcohols propanol (PrOH) and butanol (BuOH) are
      studied by x-ray Compton scattering experiments with synchrotron radiation and
      density-functional theory calculations. The lineshape of the measured spectra,
      i.e., the Compton profile, is a momentum-space property, and its changes reflect
      changes in the electronic charge density between the isomers. Compared to the
      linear alcohols (n-PrOH and n-BuOH), the Compton profiles of the branched
      alcohols (iso-PrOH, iso-BuOH, sec-BuOH) are found to be narrower, which indicates
      a more delocalized charge for the latter. The calculations are performed for
      systems consisting of one to three monomer units and are found to reproduce
      reasonably the experimental spectral features. The influence of the basis set and
      exchange-correlation scheme is studied in more detail. The results provide new
      insight into the isomeric differences in small molecule alcohols and show that
      quantum chemical calculations can be increasingly tested against the x-ray
      Compton scattering data.

PMID- 19173531
TI  - A theoretical study of the effects of the charge state and size of gold clusters
      on the adsorption and dissociation of H2.
AB  - The adsorption and dissociation of H(2) on the neutral and charged gold clusters
      Au(n) (m)(m=0,+/-1; n=1-6) is investigated using the density functional theory
      PW91 functional. H(2) interacts very weakly with Au(n) (-1), whereas the
      interaction with Au(n) (+1) is relatively strong. The binding energies on neutral
      clusters are between those on the cationic and anionic systems. The binding
      energy decreases monotonically with the size increase of the cationic clusters
      while it goes up first and then goes down on the neutral systems with the maximum
      value of 0.78 eV at Au(3). Au cations show no propensity for the dissociation
      barrier reduction and are thermodynamically unfavorable for the dissociation. For
      the first time we find that H(2) dissociation involves valley-ridge inflection
      points on some clusters. Our results indicate that H(2) dissociates facilely at
      low temperatures on both neutral and cationic Au(4) and Au(5). The phenomenon
      that H(2) dissociation was not observed experimentally is not due to the higher
      dissociation barrier and weak binding of H(2). We also show that the coordination
      number of the Au atom may not play a determining role in H(2) dissociation.

PMID- 19173532
TI  - Processing and near-field optical properties of self-assembled plasmonic
      nanoparticle networks.
AB  - We report on recent progress in the production and the deposition on surfaces of
      dielectric materials of self-assembled metallic nanoparticle systems able to
      organize into branched networks. We emphasize the interest of these new objects
      for tailoring novel near-field optical properties that could be the basis for
      optical energy transport in systems of extremely reduced sizes. The experimental
      optical spectra of such chain networks in solution can be very well reproduced by
      applying the coupled-dipole approximation scheme. In this paper, we apply this
      method to investigate the near-field optical properties of self-assembled
      plasmonic nanoparticle networks deposited on transparent surfaces.

PMID- 19173533
TI  - Interaction of Au with CeO2(111): A photoemission study.
AB  - We have studied the adsorption of low dimensional gold on ceria, produced by
      evaporation onto the surface. The interaction of gold with CeO(2)(111) layers was
      investigated with x-ray photoemission spectroscopy, ultraviolet photoemission
      spectroscopy, and resonant photoelectron spectroscopy (RPES). Gold was deposited
      in steps onto a 1.5 nm thick CeO(2)(111) layer epitaxially grown on a Cu(111)
      substrate. The RPES showed a partial Ce(4+)-->Ce(3+) reduction, observed as a
      resonant enhancement of the 4f level of the Ce(3+) species. This can be explained
      by possible creation of a new Au(+) ionic state. The observed effects are
      stronger for Au deposition at room temperature than at 250 degrees C. The
      obtained results are in agreement with already published density functional
      theory calculations reporting weakening of bond between the oxygen and the Ce
      atoms in ceria caused by the presence of gold.

PMID- 19173534
TI  - A multiscale approach for modeling the early stage growth of single and multiwall
      carbon nanotubes produced by a metal-catalyzed synthesis process.
AB  - A parametrized mesoscale model for the early stage growth of isolated single or
      multiwall carbon nanotubes (CNTs) has been developed in order to investigate the
      effects of metal catalyst particle size and composition on CNT growth mechanism
      during synthesis via a substrate-supported, catalytic chemical vapor deposition
      process. The model is based on a coarse-grained graphene sheet, represented by a
      two-dimensional simply connected triangular mesh, with parameters for the surface
      curvature, bond stretching, carbon-carbon interaction, and carbon-catalyst
      interaction determined by classical molecular dynamics simulations using a bond
      order potential derived from ab initio calculations. The mesoscale simulations
      show that the initial type of CNT growth is strongly influenced by the surface
      interaction energy between the graphene sheet and metal catalyst particle, rate
      of carbon deposition, and particle size. As expected, single wall tubes are
      produced from small catalyst particles at low deposition rates, but increasing
      the strength of carbon-catalyst interaction energy or carbon deposition rate
      results in double or even multiwall CNT structures, formed by folding or
      involution of the graphene sheet. For the range of model parameters investigated,
      all single wall CNTs with a diameter greater than 6.6 nm exhibited a kink
      collapse transition once a certain critical tube length was reached.

PMID- 19173535
TI  - Molecular dynamics simulation of the contact angle of liquids on solid surfaces.
AB  - In this work, Lennard-Jones liquid and water droplets are simulated adjacent to a
      solid surface using molecular dynamics. The contact angle is obtained by using
      direct simulation. The particle-particle particle-mesh method [B. Shi, S. Sinha,
      and V. K. Dhir, J. Phys. Chem. 124, 204715 (2006)] for long range force
      correction is used in the simulation. The contact angle is studied as a function
      of system temperature and the solid/fluid interaction potential. It is shown that
      the contact angle decreases with increasing system temperature and increases when
      the potential decreases. At high system temperature (pressure), the contact angle
      drops to zero. The predictions are compared with data from experiments and a
      reasonable agreement is found.

PMID- 19173536
TI  - The growth process of first water layer and crystalline ice on the Rh(111)
      surface.
AB  - The adsorption states and growth process of the first layer and multilayer of
      water (D(2)O) on Rh(111) above 135 K were investigated using infrared reflection
      absorption spectroscopy (IRAS), temperature programed desorption, spot-profile
      analysis low-energy electron diffraction, and scanning tunneling microscopy
      (STM). At the initial stage, water molecules form commensurate ( radical3x
      radical3)R30 degrees islands, whose size is limited for several hexagonal units;
      the average diameter is approximately 2.5 nm. This two-dimensional (2D) island
      includes D-down species, and free OD species exist at the island edge. With
      increasing coverage, the D-up species starts to appear in IRAS. At higher
      coverages, the 2D islands are connected in STM images. By the titration of Xe
      adsorption we estimated that the D-down domain occupies about 55% on Rh(111) at
      the saturation coverage. Further adsorption of water molecules forms three
      dimensional ice crystallites on the first water layer; thus, the growth mode of
      crystalline water layers on Rh(111) is a Stranski-Krastanov type. We have found
      that an ice crystallite starts to grow on D-down domains and the D-down species
      do not reorient upon the formation of a crystalline ice.

PMID- 19173537
TI  - Consistent scaling of thermal fluctuations in smoothed dissipative particle
      dynamics.
AB  - Dissipative particle dynamics (DPD) as a model of fluid particles suffers from
      the problem that it has no physical scale associated with the particles.
      Therefore, a DPD simulation requires an ambiguous fine-tuning of the model
      parameters with the physical parameters. A corrected version of DPD that does not
      suffer from this problem is smoothed dissipative particle dynamics (SDPD) [P.
      Espanol and M. Revenga, Phys. Rev. E 67, 026705 (2003)]. SDPD is, in fact, a
      version of the well-known smoothed particle hydrodynamics method, albeit with the
      proper inclusion of thermal fluctuations. Here, we show that SDPD produces the
      proper scaling of the fluctuations as the resolution of the simulation is varied.
      This is investigated in two problems: the Brownian motion of a spherical
      colloidal particle and a polymer molecule in suspension.

PMID- 19173538
TI  - Direct observation of time-dependent photoluminescence spectral shift in CdS
      nanoparticles synthesized in polymer solutions.
AB  - Direct observation of time-resolved emission spectra (TRESs) of cadmium sulfide
      nanoparticles in polymer solutions was carried out with picosecond resolution
      using a streak camera. The TRESs were found to undergo a pronounced time
      dependent Stokes shift, eventually coinciding with the steady-state
      photoluminescence spectra within an approximately 40 ns delay time. Moreover,
      approximately 90% of the shift was complete within the first 1 ns after
      excitation, in contrast to the fact that overall photoluminescence involves very
      long time constants of 10-100 ns. The observed Stokes shift dynamics was very
      similar in CdS nanoparticles stabilized in two very different types of polymer
      solutions. Thus the solvent and/or polymeric stabilizer appeared to have a
      minimal effect on the shift. We propose that the relaxation proceeds through an
      internal mechanism involving the fast decay of high-energy traps into relatively
      slow-decaying low-energy traps. Time-dependent photoluminescence anisotropy
      experiments also revealed an approximately 1 ns decay component appearing only in
      the higher-energy end of the photoluminescence spectrum. Because this time
      constant is too short to represent rotational diffusion of the nanometer-sized
      particles, it was associated with the rapid relaxation of the high-energy trap
      states.

PMID- 19173539
TI  - Characterization of anisotropic poly(vinyl alcohol) hydrogel by small- and ultra
      small-angle neutron scattering.
AB  - Poly(vinyl alcohol) (PVA) hydrogels are formed from PVA solution when physical
      cross-links form during freeze/thaw cycling. By applying a stress during the
      freeze/thaw process, PVA hydrogels with anisotropic mechanical properties are
      produced. We have used small- and ultra-small-angle neutron scattering to study
      the structure at length scales of 2 nm to 10 mum. By supplementing the neutron
      data with data from atomic force microscopy, we have probed a large range of
      length scales within which structural changes responsible for bulk anisotropy
      occur. We model the gel as interconnected PVA blobs of size 20-50 nm arranged in
      fractal aggregates extending to micrometers or tens of micrometers. Bulk
      mechanical anisotropy appears to be due to the alignment of blobs and connections
      between blobs. This information is essential for tailoring mechanical properties
      for applications where anisotropy is desirable such as to match the properties of
      natural tissue in coronary grafts and to control diffusive properties in active
      wound dressings.

PMID- 19173540
TI  - Evaluating the transferability of coarse-grained, density-dependent implicit
      solvent models to mixtures and chains.
AB  - Previously, we described a coarse-graining method for creating local density
      dependent implicit solvent (DDIS) potentials that reproduce the radial
      distribution function (RDF) and solute excess chemical potential across a range
      of particle concentrations [E. C. Allen and G. C. Rutledge, J. Chem. Phys. 128,
      154115 (2008)]. In this work, we test the transferability of these potentials,
      derived from simulations of monomeric solute in monomeric solvent, to mixtures of
      solutes and to solute chains in the same monomeric solvent. For this purpose,
      "transferability" refers to the predictive capability of the potentials without
      additional optimization. We find that RDF transferability to mixtures is very
      good, while RDF errors in systems of chains increase linearly with chain length.
      Excess chemical potential transferability is good for mixtures at low solute
      concentration, chains, and chains of mixed composition; at higher solute
      concentrations in mixtures, chemical potential transferability fails due to the
      nature of the DDIS potentials, in which particle insertion directly affects the
      interaction potential. With these results, we demonstrate that DDIS potentials
      derived for pure solutes can be used effectively in the study of many important
      systems including those involving mixtures, chains, and chains of mixed
      composition in monomeric solvent.

PMID- 19173541
TI  - Structural relaxations of phospholipids and water in planar membranes.
AB  - We have used dielectric spectroscopy and temperature modulated differential
      scanning calorimetry (TMDSC) to investigate the structural relaxation processes
      and phase transitions of water and lipids in multilamellar, planar phospholipids.
      At low hydration levels we observe the main structural relaxation related to the
      glass transition of the phospholipids. With increasing water content a more
      pronounced pretransition, attributed to a gel to ripple phase transition, is
      observed in the TMDSC data. In the proximity of this pretransition, a distinct
      change in the temperature dependence or alternatively a bifurcation into two
      processes is observed in the dielectric data. Around this temperature a crossover
      in the long-range ionic conductivity across the membranes is also observed, which
      is one of the key parameters for biological membranes. Thus, the major dynamical
      changes do not occur at the main, i.e., the gel to liquid structural phase
      transition, but at a pretransition that occurs roughly 20 K below the main
      transition.

PMID- 19173543
TI  - Comment on "Residual multiparticle entropy does not generally change sign near
      freezing" [J. Chem. Phys. 128, 161101 (2008)].
AB  - Does the vanishing of the residual multiparticle entropy, a quantity defined as
      the cumulative contribution of more-than-two-particle density correlations to the
      excess entropy of a fluid, have physical significance? We address this question
      in the light of the arguments presented in the paper that is being commented on
      and of the phenomenology thus far explored in a variety of model systems
      undergoing thermodynamic or structural transformations into more ordered (but not
      necessarily crystalline) states or regimes.

PMID- 19173542
TI  - Simulations of nucleation and elongation of amyloid fibrils.
AB  - We present a coarse-grained model for the growth kinetics of amyloid fibrils from
      solutions of peptides and address the fundamental mechanism of nucleation and
      elongation by using a lattice Monte Carlo procedure. We reproduce the three main
      characteristics of nucleation of amyloid fibrils: (1) existence of lag time, (2)
      occurrence of a critical concentration, and (3) seeding. We find the nucleation
      of amyloid fibrils to require a quasi-two-dimensional configuration, where a
      second layer of beta sheet must be formed adjunct to a first layer, which in turn
      leads to a highly cooperative nucleation barrier. The elongation stage is found
      to involve the Ostwald ripening (evaporation-condensation) mechanism, whereby
      bigger fibrils grow at the expense of smaller ones. This new mechanism reconciles
      the debate as to whether protofibrils are precursors or monomer reservoirs. We
      have systematically investigated the roles of time, peptide concentration,
      temperature, and seed size. In general, we find that there are two kinds of lag
      time arising from two different mechanisms. For higher temperatures or low enough
      concentrations close to the disassembly boundary, the fibrillization follows the
      nucleation mechanism. However, for low temperatures, where the nucleation time is
      sufficiently short, there still exists an apparent lag time due to slow Ostwald
      ripening mechanism. Consequently, the lag time is nonmonotonic with temperature,
      with the shortest lag time occurring at intermediate temperatures, which in turn
      depend on the peptide concentration. While the nucleation dominated regime can be
      controlled by seeding, the Ostwald ripening regime is insensitive to seeding.
      Simulation results from our coarse-grained model on the fibril size, lag time,
      elongation rate, and solubility are consistent with available experimental
      observations on many specific amyloid systems.

PMID- 19173548
TI  - Sublethal effects of subacute exposure to RDX (1,3,5-trinitro-1,3,5-triazine) in
      the northern bobwhite (Colinus virginianus).
AB  - Northern bobwhite (Colinus virginianus) were orally exposed via gavage to 0, 0.5,
      3, 8, 12, or 17 mg/kg of RDX (1,3,5-trinitro-1,3,5-triazine) in corn oil daily
      for 14 d to evaluate sublethal effects of this explosive in birds. Mortality
      occurred at a rates of 100, 67, and 25% for the 17, 12, and 8 mg/kg/d dose
      groups, respectively. Death was preceded by clonic and tonic convulsions and
      weight loss caused by gastrointestinal effects. Increases in serum globulin and
      total leukocytes were observed in the two highest-dose groups. Degeneration of
      testicular and splenic tissue also was observed. The no-observed-adverse-effects
      and lowest-observed-adverse-effects levels were determined as 3.0 and 8.0
      mg/kg/d, respectively.

PMID- 19173549
TI  - Concentrations of selenium and mercury in eared grebes (Podiceps nigricollis)
      from Utah's Great Salt Lake, USA.
AB  - We examined selenium and mercury concentrations in eared grebes (Podiceps
      nigricollis) that spent the fall of 2006 on the Great Salt Lake (UT, U.S.A.),
      where their diet consisted mainly of brine shrimp (Artemia franciscana). Selenium
      concentrations in livers varied based on when the grebes were collected (lower in
      September [mean +/- standard error, 9.4 +/- 0.7 microg/g dry wt] than in November
      [14.5 +/- 1.4 microg/g]), on where the birds were collected on the Great Salt
      Lake (Antelope Island, 8.6 +/- 0.5 +/- microg/g; Stansbury Island, 15.2 +/- 1.4
      microg/g), and on the grebe's age (juveniles, 8.5 +/- 1.5 mcirog/g; adults, 15.8
      +/- 1.3 microg/g), but not by sex. Selenium concentrations in blood differed only
      by collection site (Antelope Island, 16.8 +/- 2.3 microg/g; Stansbury Island,
      25.4 +/- 3.0 microg/g). Mercury concentration in the blood of grebes varied by
      when the grebes were collected (September, 5.6 +/- 0.5 microg/g; November, 8.4 +/
      1.2 microg/g), where the birds were collected (Antelope Island, 4.3 +/- 0.5
      microg/g; Stansbury Island, 10.1 +/- 2.6 microg/g), and the grebe's age
      (juveniles, 5.5 +/- 0.8 microg/g; adults, 8.4 +/- 1.0 microg/g), but not by sex.
      Selenium concentrations in blood were correlated with selenium concentrations in
      the liver and with mercury concentrations in both blood and liver. Body mass of
      grebes increased dramatically from September (381 +/- 14 g wet wt) to November
      (591 +/- 11 g). Body, liver, and spleen mass either were not correlated with
      selenium or mercury concentrations or the relationship was positive. These
      results suggest that high mercury and selenium levels were not preventing grebes
      from increasing or maintaining mass.

PMID- 19173550
TI  - Validation of the target lipid model for toxicity assessment of residual
      petroleum constituents: monocyclic and polycyclic aromatic hydrocarbons.
AB  - A method is presented for developing scientifically defensible, numeric
      guidelines for residual petroleum-related constituents, specifically monocyclic
      aromatic hydrocarbons (MAHs) and polycyclic aromatic hydrocarbons (PAHs), in the
      water column. The guidelines are equivalent to a HC5 (i.e., hazard concentration
      to 5% of the tested species, or the concentration that protects 95% of the tested
      species). The model of toxicity used in this evaluation is the target lipid model
      (TLM) that was developed for assessing the toxicity of type I narcotic chemicals.
      An acute to chronic ratio is used for chronic expression and sublethal effects.
      The TLM is evaluated by comparing predicted and observed toxicity of these
      petroleum components. The methodology is capable of predicting both the acute and
      chronic toxicity of MAHs and PAHs in single exposures and in mixtures. For acute
      exposures, the TLM was able to predict the toxicity to within a factor of three
      to five. The use of toxic units was an effective metric for expressing the
      toxicity of mixtures. Within the uncertainty bounds, the TLM correctly predicted
      where sublethal effects of edemas, hemorrhaging, and other abnormalities were
      observed to occur in early life-stage exposure to PAHs. The computed HC5s were
      lower than no-observed-effect concentrations based on growth, reproduction, and
      mortality endpoints and sublethal effects. The methodology presented can be used
      by the oil spill community to compare residual concentrations of PAHs against
      defensible, numeric guidelines to assess potential ecological impacts.

PMID- 19173555
TI  - Highly regioselective simultaneous introduction of phosphino and seleno groups
      into unsaturated bonds by the novel combination of (Ph2P)2 and (PhSe)2 upon
      photoirradiation.
AB  - A novel combination of tetraphenyldiphosphine and diphenyl diselenide under
      photoirradiation conditions attains simultaneous introduction of
      diphenylphosphino and phenylseleno groups into carbon-carbon unsaturated bonds
      such as terminal alkynes or allenes, regioselectively.

PMID- 19173556
TI  - Conversion of Weinreb amides into benzene rings incorporating the amide carbonyl
      carbon.
AB  - Esters, acids and acid chlorides can be converted via the intermediacy of their
      corresponding Weinreb amides into benzene derivatives that incorporate the
      original carbonyl carbon as part of the benzene ring. The process involves
      treatment of the derived Weinreb amides with 3-butenylmagnesium bromide and an
      allylic Grignard reagent, followed by ring-closing metathesis, dehydration and
      dehydrogenation. The dehydration-dehydrogenation can be done under acidic
      conditions with a mixture of TsOH x H(2)O and DDQ or in two steps with
      SOCl(2)/pyridine, followed by treatment with DDQ. Application of the method to
      carbohydrates provides a convenient route to C-5 aryl pyranosides.

PMID- 19173557
TI  - Effect of swelling ratio of injectable hydrogel composites on chondrogenic
      differentiation of encapsulated rabbit marrow mesenchymal stem cells in vitro.
AB  - An injectable, biodegradable hydrogel composite of oligo(poly(ethylene glycol)
      fumarate) (OPF) and gelatin microparticles (MPs) has been investigated as a cell
      and growth factor carrier for cartilage tissue engineering applications. In this
      study, hydrogel composites with different swelling ratios were prepared by cross
      linking OPF macromers with poly(ethylene glycol) (PEG) repeating units of varying
      molecular weights from 1000 approximately 35000. Rabbit marrow mesenchymal stem
      cells (MSCs) and MPs loaded with transforming growth factor-beta1 (TGF-beta1)
      were encapsulated in the hydrogel composites to examine the effect of the
      swelling ratio of the hydrogel composites on the chondrogenic differentiation of
      encapsulated rabbit marrow MSCs both in the presence and in the absence of TGF
      beta1. The swelling ratio of the hydrogel composites increased as the PEG
      molecular weight in the OPF macromers increased. Chondrocyte-specific genes were
      expressed at higher levels in groups containing TGF-beta1-loaded MPs and varied
      with the swelling ratio of the hydrogel composites. OPF hydrogel composites with
      PEG repeating units of molecular weight 35000 and 10000 with TGF-beta1-loaded MPs
      exhibited a 159 +/- 95- and a 89 +/- 31-fold increase in type II collagen gene
      expression at day 28, respectively, while OPF hydrogel composites with PEG
      repeating units of molecular weight 3000 and 1000 with TGF-beta1-loaded MPs
      showed a 27 +/- 10- and a 17 +/- 7-fold increase in type II collagen gene
      expression, respectively, as compared to the composites with blank MPs at day 0.
      The results indicate that chondrogenic differentiation of encapsulated rabbit
      marrow MSCs within OPF hydrogel composites could be affected by their swelling
      ratio, thus suggesting the potential of OPF composite hydrogels as part of a
      novel strategy for controlling the differentiation of stem cells.

PMID- 19173558
TI  - Cyclodextrin and polysaccharide-based nanogels: entrapment of two hydrophobic
      molecules, benzophenone and tamoxifen.
AB  - The entrapment of two hydrophobic molecules, benzophenone and tamoxifen, into
      self-assembling cyclodextrin (CD)-based nanogels has been studied. These nanogels
      formed spontaneously upon the association of a hydrophobically modified dextran
      (MD) and a cyclodextrin polymer (pbetaCD). The interactions of benzophenone and
      tamoxifen with MD and pbetaCD were investigated using phase solubility studies,
      circular dichroism, and isothermal titration calorimetry. Both hydrophobic
      molecules were included into the CD cavities of the pbetaCD and were also
      solubilized by MD into its hydrophobic microdomains. We took advantage of these
      interactions to form benzophenone- and tamoxifen-loaded nanogels. The highest
      benzophenone loadings were obtained by solubilizing it in both pbetaCD and MD
      solutions before mixing them to form nanogels. These studies open new
      possibilities of applications of the nanogels, mainly in the cosmetic field, as
      sun screen carriers prepared by a simple "green" technology.

PMID- 19173559
TI  - CuO nanoparticles catalyzed C-N, C-O, and C-S cross-coupling reactions: scope and
      mechanism.
AB  - CuO nanoparticles have been studied for C-N, C-O, and C-S bond formations via
      cross-coupling reactions of nitrogen, oxygen, and sulfur nucleophiles with aryl
      halides. Amides, amines, imidazoles, phenols, alcohols and thiols undergo
      reactions with aryl iodides in the presence of a base such as KOH, Cs(2)CO(3),
      and K(2)CO(3) at moderate temperature. The procedure is simple, general, ligand
      free, and efficient to afford the cross-coupled products in high yield.

PMID- 19173560
TI  - Monolayer resist for patterned contact printing of aligned nanowire arrays.
AB  - Large-area, patterned printing of nanowires by using fluorinated self-assembled
      monolayers as the resist layer is demonstrated. By projecting a light pattern on
      the surface of the monolayer resist in an oxygen-rich environment, sticky and
      nonsticky regions on the surface are directly defined in a single-step process
      which then enables the highly specific and patterned transfer of the nanowires by
      the contact printing process, without the need for a subsequent lift-off step.
      This work demonstrates a simple route toward scalable, patterned printing of
      nanowires on substrates by utilizing light-tunable, nanoscale chemical
      interactions and demonstrates the versatility of molecular monolayers for use as
      a resist layer.

PMID- 19173562
TI  - Morpholino, piperidino, and pyrrolidino derivatives of pyrimidine nucleosides as
      inhibitors of ribonuclease A: synthesis, biochemical, and crystallographic
      evaluation.
AB  - Six 5'-deoxy-5'-morpholine, piperidine, and pyrrolidine of pyrimidine nucleosides
      have been synthesized and characterized. Their inhibitory action to ribonuclease
      A has been studied by biochemical analysis and X-ray crystallography. These
      compounds are moderate inhibitors of RNase A with mid-to-upper micromolar
      inhibition constants (K(i)). The high resolution X-ray crystal structures of the
      RNase A-inhibitor complexes have shown that all inhibitors bind at the enzyme
      catalytic cleft with the pyrimidine nucleobase at the B(1)R(2) subsites while the
      5' group binds away from the main subsite P(1), where P-O(5') bond cleavage
      occurs, toward the solvent close to subsite P(0). Structure-activity relationship
      analysis has demonstrated that the compounds with the larger group in the 5'
      position are more potent. Comparative structural analysis of these RNase A
      complexes with other similar RNase A-ligand complexes provides a structural
      explanation of their potency and suggests ways to improve their efficiency and
      selectivity. These inhibitors can be the starting point for the development of
      compounds that can be used as pharmaceuticals against pathologies associated with
      RNase A homologues such as human angiogenin, which is implicated in tumor induced
      neovascularization.

PMID- 19173563
TI  - NMR measure of translational diffusion and fractal dimension. Application to
      molecular mass measurement.
AB  - Experimental NMR diffusion measure on polymers and on globular proteins are
      presented. These results, complemented with results found in the literature,
      enable a general description of effective fractal dimension for objects such as
      small organic molecules, sugars, polymers, DNA, and proteins. Results are
      compared to computational simulations as well as to theoretical values. A global
      picture of the diffusion phenomenon emerges from this description. A power law
      relating molecular mass with diffusion coefficients is described and found to be
      valid over 4 orders of magnitude. From this law, the fractal dimension of the
      molecular family can be measured, with experimental values ranging from 1.41 to
      2.56 in full agreement with theoretical approaches. Finally, a method for
      evaluating the molecular mass of unknown solutes is described and implemented as
      a Web page.

PMID- 19173564
TI  - Electrochemical and theoretical investigation of corannulene reduction processes.
AB  - The voltammetric generation of corannulene anions was investigated over a large
      range of experimental conditions comprising either "traditional" electrochemical
      solvents, such as dimethylformamide, acetonitrile, and tetrahydrofuran, or
      "unconventional" solvents, such as liquid ammonia, liquid methylamine, or liquid
      dimethylamine, and several different supporting electrolytes. Strong ion pairing
      effects were found to dominate the electrochemical generation of corannulene
      higher anions, and through the suitable choice of the solvent/electrolyte system,
      we observed, for the first time, the reversible electrochemical generation of up
      to the triply reduced corannulene. The standard potentials obtained
      experimentally compared rather well with the theoretical values calculated by ab
      initio and density functional methods, in which solvation and ion pairing effect
      were explicitly taken into account. In particular, the calculations considered
      the effect of the electrolyte cation size on ion pairing in order to rationalize
      the occurrence of the third reduction within the experimental potential window.

PMID- 19173565
TI  - Spontaneous polarization of the neutral interface for valence asymmetric
      coulombic systems.
AB  - In this paper, we discuss the phenomenon of a spontaneous polarization of a
      neutral hard planar interface for valence asymmetric Coulombic systems. Within a
      field theoretical description, we account for the existence of nontrivial charge
      density and electric potential profiles. The analysis of the phenomenon shows
      that the effect is related to combinatorics in relation with the existence of the
      two independent species cations and anions. This simple and basic feature is
      related to the quantum mechanical properties of the system. The theoretical
      results are compared with numerical simulations data and are shown to be in very
      good agreement, which a fortiori justifies our physical interpretation.

PMID- 19173566
TI  - pH-dependent structures of an i-motif DNA in solution.
AB  - We have investigated for the first time the structure of i-motif DNA in solution
      at various pH conditions by using synchrotron small-angle X-ray scattering
      technique. To facilitate direct structural comparison between solution structures
      of i-motif DNA at various pH values, we created atomic coordinates of i-motif DNA
      from a fully folded to unfolded atomic model. Under mild acidic conditions, the
      conformations for i-motif DNA appeared to be similar to that of the partially
      unfolded i-motif atomic model in overall shape, rather than the fully folded i
      motif atomic model. Collectively, our observations indicate that i-motif DNA
      molecule is structurally dynamic over a wide pH range, adopting multiple
      conformations ranging from the folded i-motif structure to a random coil
      conformation. As the i-motif structure has been used as an important component in
      nanomachines, we can therefore believe that the structural evidence presented
      herein will promote the development of future DNA-based molecular-actuator
      devices.

PMID- 19173568
TI  - Thermal denaturation of hydrated wool keratin by 1H solid-state NMR.
AB  - Thermal denaturation of hydrated keratin in wool was investigated by NMR using 1H
      wide-line spectra to obtain the phase composition and 1H spin-diffusion
      experiments using a double-quantum filter to obtain the domain sizes for the wool
      fibers. The denaturation process detected by DSC takes place for wool fibers in
      deuterated water in the temperature range 140-144 degreeC. The phase composition
      measured by 1H wide line NMR spectra reveals a rigid, semirigid and an amorphous
      phase for temperatures in the range 25-160 degreeC. A dramatic change in the
      phase composition was detected around 142 degreeC, corresponding to the
      denaturation temperature. The morphological domain sizes measured by 1H spin
      diffusion NMR experiments were obtain from the solutions of the spin-diffusion
      equations for two-dimensional rectangular and cylindrical morphologies. The
      keratin mobility gradient in the interfacial region at different denaturation
      temperatures was measured from the 1H spin-diffusion data. A qualitative model
      describing the denaturation process of hydrated keratin protein was developed
      that explains the changes in domain thickness, spin diffusivities, phase
      composition, and thermodynamic parameters.

PMID- 19173569
TI  - Vibrational dynamics of iron in cytochrome C.
AB  - Nuclear resonance vibrational spectroscopy (NRVS) and Raman spectroscopy on
      (54)Fe- and (57)Fe-enriched cytochrome c (cyt c) identify multiple bands
      involving vibrations of the heme Fe. Comparison with predictions from Fe isotope
      shifts reveals that 70% of the NRVS signal in the 300-450 cm(-1) frequency range
      corresponds to vibrations resolved in Soret-enhanced Raman spectra. This
      frequency range dominates the "stiffness", an effective force constant determined
      by the Fe vibrational density of states (VDOS), which measures the strength of
      nearest-neighbor interactions with Fe. The stiffness of the low-spin Fe
      environment in both oxidation states of cyt c significantly exceeds that for the
      high-spin Fe in deoxymyoglobin, where the 200-300 cm(-1) frequency range
      dominates the VDOS. This situation is reflected in the shorter Fe-ligand bond
      lengths in the former with respect to the latter. The longer Fe-S(Met80) in
      oxidized cyt c with respect to reduced cyt c leads to a decrease in the stiffness
      of the iron environment upon oxidation. Comparison with NRVS measurements allows
      us to assess assignments for vibrational modes resolved in this region of the
      heme Raman spectrum. We consider the possibility that the 372 cm(-1) band in
      reduced cyt c involves the Fe-S(Met80) bond.

PMID- 19173570
TI  - Multiscale modeling catalytic decomposition of hydrocarbons during carbon
      nanotube growth.
AB  - A molecular dynamics simulator coupled to a quantum semiempirical Hamiltonian
      model was applied to multiscale modeling of the catalytic decomposition of
      hydrocarbons during carbon nanotube (CNT) and carbon nanofiber (CNF) growth. It
      was found that catalytic decomposition of acetylene is accompanied by a large
      energy release and its rate weakly depends on temperature in the range from 20 to
      700 degrees C. In contrast, the methane decomposition rate substantially
      decreases as the iron temperature drops. A comparative analysis of acetylene
      decomposition on a clean surface and on an oxidized Fe(100) surface showed that
      the presence of oxygen reduces the decomposition rate by an order of magnitude,
      but has very little influence on the amount of heat released by the reaction. We
      also found that oxygen absorbed on the surface of catalyst does not easily
      diffuse into the catalyst or desorb from the surface. This implies that the
      surface of the catalyst is quickly covered by oxygen during CNT/CNF growth even
      at low oxygen flow rates.

PMID- 19173571
TI  - Factors controlling the stability of a kinetically hindered lamellar-lamellar
      transition.
AB  - We show that we can manipulate the stability of a metastable gel phase, either to
      enhance its transitory nature or to "lock" it in. Using simple additives such as
      salt and fatty alcohol we were able to examine both the long-range effect, acting
      between charged bilayers, and short-range effects on the metastability. We found
      that the addition of salt to the cationic surfactant diethanolamine ester
      dimethyl ammonium chloride destabilized the gel phase, and at high concentrations
      it was able to decrease the length of time taken for the gel phase to revert to a
      hydrated solid "coagel" phase by an order of magnitude. The growth of the coagel
      phase was also found to be affected by increasing salt concentration, changing
      from needle-like (1D) to spherical growth. In contrast to the marked
      destabilization of the gel phase by salt, the addition of 1-octadecanol was found
      to prolong the lifetime of the gel phase almost indefinitely by disrupting the
      short-range packing between the surfactant molecules. This suggests that
      counterion binding plays a major role in the stability of metastable lamellar gel
      phases.

PMID- 19173572
TI  - Diffusion of molecules in ionic liquids/organic solvent mixtures. Example of the
      reversible reduction of O2 to superoxide.
AB  - Transport properties of molecules dissolved in room-temperature ionic liquids are
      highly sensitive to the charge carried by the molecule because of complex ion-ion
      interactions that could be tuned by addition of a cosolvent. In this connection,
      the one-electron reduction of oxygen was used as a probe system for studying the
      effects of the addition of a cosolvent such as dimethylformamide (DMF) into a
      pure ionic liquid (triethylbutylammonium bis(trifluoromethylsulfonyl)imide)
      ([Et(3)BuN][NTf(2)]) on the diffusion of charged species versus neutral species.
      Experimental data about the diffusion coefficients of O(2) (D(O(2))) and O(2)(*-)
      (D(O)((2)(*-))) and their ratios (gamma = D(O)((2)(*-))/D(O(2))) were extracted
      using scanning electrochemical microscopy (SECM) in transient mode as a function
      of the DMF concentration. The ratio gamma and both of the diffusion coefficients
      D(O)((2))(*-) and D(O(2)) were found to increase exponentially with the DMF
      volume fractions following the same general tendency described for the viscosity.
      However, D(O)((2))(*-) varies on a much larger range than D(O)((2)) (around 1000
      times more), and O(2)(*-) retains an almost "pure ionic" behavior for higher DMF
      fractions. All of these results support the occurrence of a sharp transformation
      in the bonding character of the RTIL cation upon addition of a molecular solvent,
      as predicted in recent theoretical simulations.

PMID- 19173573
TI  - Visual sandwich immunoassay system on the basis of plasmon resonance scattering
      signals of silver nanoparticles.
AB  - In this contribution, we established a sandwich immunoassay system with a common
      spectrofluorometer to collect the plasmon resonance scattering (PRS) signals from
      silver nanoparticles (AgNPs) immunotargeted on glass slides. By taking the
      immunoreactions of goat antihuman IgG (Fc fragment specific) antibody (GAH-IgG),
      human immunoglobulin (H-IgG), and rabbit antihuman IgG (Fab fragment specific)
      antibody (RAH-IgG) as an example, we found that if a primary antibody (GAH-IgG)
      was first immobilized on the surface of glass slides and applied to capture
      target antigen (H-IgG), AgNPs-labeled secondary antibody (RAH-IgG) could be
      employed to detect the target antigen (H-IgG) by forming a sandwich immune
      complex on the surface of the glass slide. It was found that the PRS signals
      resulting from the AgNPs immunotargeted on the glass slides could be applied to
      the quantitative detection of H-IgG target antigen in the range of 10-1000 ng/mL
      with the limit of determination of 1.46 ng/mL (3sigma) under optimal conditions,
      which is sensitive and comparable with reported chemiluminescence immunoassays.
      With a dark-field microscope coupled with a spectral system, we measured the PRS
      features of single AgNPs immunotargeted on the glass slides, showing that the PRS
      of single nanoparticles might have potential applications in analytical
      chemistry. Further findings showed that the strong PRS signals from the AgNPs
      immunotargeted on the glass slides can be clearly seen and distinguished by naked
      eyes under the excitation of a common white light-emitting diode (LED) torch.
      Therefore, a visual PRS immunoassay system can be established easily with common
      glass slides and an LED torch.

PMID- 19173574
TI  - Multiplexed four-channel rectilinear ion trap mass spectrometer.
AB  - A four-channel multiplexed mass spectrometer with rectilinear ion trap (RIT) mass
      analyzers was designed, constructed, and characterized. The system consists of
      four parallel atmospheric pressure ion (API) sources, four RIT mass analyzers,
      four sets of ion optical elements, and four conversion dynode detectors. The
      complete instrument is housed in a single vacuum manifold with a common vacuum
      system. It has a relatively small footprint, and costs and complexity were
      minimized and controls simplified by sharing the electronics and control modules
      among different channels. Each channel of the instrument can be operated in
      either positive or negative ion mode with a choice of ionization methods to
      improve the information content from an experiment. Also, the instrument is
      equipped with simultaneous data acquisition capabilities from all four channels,
      but the use of a common RF electronics system limits the degree to which the
      analyzer channels can be scanned independently. The instrument was characterized
      over the mass/charge range of 150 to 1300 Th. Mass misassignments in different
      ion traps because of machining and assembly tolerances were avoided by the
      application of supplementary direct current signals to each mass analyzer to
      correct mass offsets. A multiplexed automatic gain control (AGC) scheme was
      developed to control the ion population in each of the traps independently. These
      two features allow tandem mass spectrometry to be performed with an isolation
      window of 1 Th so trapping identical ions in all four channels. There are two
      principal modes of operation. In one, the same sample is analyzed in all four
      channels using different ionization methods to increase the information content
      of the analysis. In the other mode of operation, different samples are analyzed
      in all four channels with the same ionization method, so providing higher
      throughput. These capabilities were demonstrated by examining lipids produced by
      Escherichia coli and complex mixtures containing drugs of abuse.

PMID- 19173575
TI  - Tunable antimicrobial polypropylene surfaces: simultaneous attachment of
      penicillin (Gram +) and gentamicin (Gram -).
AB  - Surface reactions were performed on polypropylene (PP) surfaces to retard the
      simultaneous growth of Staphylococcus aureus (S. aureus) and Pseudomonas putida
      (P. putida) bacteria. Microwave plasma reactions in the presence of maleic
      anhydride (MA) resulted in the formation of acid groups on the surface of PP.
      Such surfaces were further modified by conducting two parallel reactions: (1)
      poly(ethylene glycol) (PEG) was attached to COOH groups of the PP surface,
      followed by penicillin V (PEN) reactions to target S. aureus destruction and (2)
      diglycidyl PEG was attached, followed by gentamicin (GEN) reactions, to create
      antimicrobial surfaces targeted at P. putida . Simultaneous gram "+" and gram "-"
      resistance was obtained by varying the PEN/GEN ratios on such modified PP
      surfaces, thus providing the controllable degree of gram "+" and gram "-"
      antimicrobial strength. While spectroscopic analyses revealed chemical
      attachments of PEN and GEN, the effectiveness against proliferation of S. aureus
      (Gram +) and P. putida (Gram -) bacteria was determined using liquid culture
      tests. These studies show for the first time the formation of tunable
      antimicrobial polypropylene surfaces with controllable strength.

PMID- 19173576
TI  - Pseudorotation in radical cations of low-symmetric decalin molecules.
AB  - Adiabatic potential energy surfaces (PES) of isomeric decalin cations have been
      found to be the pseudorotational surfaces due to avoided crossing that is typical
      for the highly symmetric Jahn-Teller active ions rather than for low-symmetric
      bicyclic systems. According to the UB3LYP/6-31G* data, the height of the barrier
      to pseudorotation is less than 2 kcal/mol for the trans isomer and about 9
      kcal/mol for the cis isomer. Another peculiarity of the cis isomer PES is that
      the structure of minimum energy lies beyond the pseudorotation gutter. The
      calculation results are in fair agreement with the experimental electron spin
      resonance data.

PMID- 19173577
TI  - Theoretical analysis on the transition state of the anticancer drug trans
      [PtCl2(isopropylamine)2] and its cis isomer binding to DNA purine bases.
AB  - The first and second substitution reactions between hydrolyzed trans/cis
      [PtCl(2)(isopropylamine)(2)], trans/cis-[Pt(isopropylamine)(2)Cl(H(2)O)](+), and
      trans/cis- [Pt(isopropylamine)(2)(H(2)O)(2)](2+) and purine bases guanine and
      adenine are explored using the B3LYP hybrid functional and IEF-PCM solvation
      models. For the first substitution, the calculated lowest free energy barrier is
      11.4/12.2kcal/mol (from trans-Pt-chloroaqua complex to trans/cis-monoadduct) for
      guanine, and 14.2/14.2kcal/mol (from trans-Pt-chloroaqua complex to trans/cis
      monoadduct) for adenine. The computed lowest free energy barrier of monoaquated
      complexes is always lower than that of diaquated complexes in the first
      substitution. Our calculations for the first substitution demonstrate, for the
      first time, that the trans reactant complexes (or isolated reactants) can
      generate trans- or cis-monoadducts via identical or very similar trigonal
      bipyramidal transition-state structures, suggesting that the monoadducts can
      subsequently close to form the bifunctional intrastrand Pt-DNA adducts and
      simultaneously distort DNA in the same way as cisplatin. Our calculations confirm
      that the transplatin analogue leads to conformational alterations in double
      helical DNA similar to those induced by cisplatin. In other words, it is likely
      that the transplatin analogue has the same mechanism of action as cisplatin
      binding to DNA targets. For the second substitution, the
      Pt(isopropylamine)(2)GA(2+) head-to-tail path has the lowest free energy of
      activation at 17.2 kcal/mol, closely followed by the Pt(isopropylamine)(2)GG(2+)
      head-to-tail path at 23.7 kcal/mol when the monofunctional cis-Pt-G complex
      serves as the reactant, while the Pt(isopropylamine)(2)GA(2+) head-to-head adduct
      has the lowest barrier of 13.3kcal/mol, closely followed by the
      Pt(isopropylamine)(2)GG(2+) head-to-head adduct at 17.6 kcal/mol if the
      monofunctional trans-Pt-G complex is the reactant. The theoretically determined
      activation energy is lower than that of cisplatin, which confirms that trans
      [PtCl(2)(isopropylamine)(2)] is a potential anticancer drug as suggested by
      experiment. The structural analysis for reactant complexes, product complexes,
      and transition states shows that hydrogen bonds play an important role in
      stabilizing these species for the first and second substitution.

PMID- 19173580
TI  - Depth-dependent dissociation of nitric acid at an aqueous surface: Car-Parrinello
      molecular dynamics.
AB  - The acid dissociation of a nitric acid HNO(3) molecule located at various depths
      in a water slab is investigated via Car-Parrinello molecular dynamics
      simulations. HNO(3) is found to remain molecular when it is adsorbed on top of
      the surface with two hydrogen-bonds, and to dissociate--although not always--by
      transferring a proton to a water molecule within a few picoseconds when embedded
      at various depths within the aqueous layer. The acid dissociation events are
      analyzed and discussed in terms of the proton donor-acceptor O-O hydrogen bonding
      distance and the configurations of the nearest-neighbor solvent waters of an
      HNO(3).H(2)O pair. Four key structural features for the HNO(3) acid dissociation
      are identified and employed to analyze the trajectory results. Key solvent
      motions for the dissociation include the decrease of the proton donor-acceptor O
      O hydrogen bonding distance and a 4 to 3 coordination number change for the
      proton-accepting water. The Eigen cation (H(3)O(+)), rather than the Zundel
      cation (H(5)O(2)(+)), is found to be predominant next to the NO(3)(-) ion in
      contact ion pairs in all cases.

PMID- 19173578
TI  - Bulk and interfacial aqueous fluoride: an investigation via first principles
      molecular dynamics.
AB  - Using first principles molecular dynamics simulation, we have studied a fluoride
      anion embedded in a periodically replicated water slab composed of 215 water
      molecules to mimic both bulk and interfacial solvation. In contrast to some
      recent experiments, our findings suggest that there are only small structural
      changes for fluoride and its first solvation shell in the bulk. Moreover, the
      presence of fluoride does not significantly alter the rotational dynamics of
      nearby water. In addition, we have computed the molecular dipole moments using
      Wannier centers. At the interface, the presence of fluoride increases the
      molecular dipole moments of nearby water molecules, whereas in the bulk, the
      dipole moments for water appear to be essentially invariant to the presence of
      fluoride in the vicinity. Previous studies of the air-water interface have showed
      interfacial water to have higher average HOMO energies and, thus, likely to be
      more prone to electrophilic attack. With the addition of fluoride, the most
      likely reactive site for electrophilic reactions shifts to the anion. This
      finding could explain the known large increase in reaction rates for
      heterogeneous process of interest in atmospheric science. The reactive properties
      of other anions near the air-water interface are of general interest in
      heterogeneous chemistry and can be elucidated using a similar type of analysis,
      as performed here for the fluoride anion.

PMID- 19173579
TI  - The scaffold protein PDZK1 undergoes a head-to-tail intramolecular association
      that negatively regulates its interaction with EBP50.
AB  - PDZK1 (also known as CAP70, NHERF3, or NaPi-Cap1) is a scaffolding protein
      composed of four PDZ (Post-Synaptic Density-95, Discs Large, Zonula Occludens-1)
      domains followed by a short carboxyl-terminal tail. This scaffold acts as a
      mediator of localization and expression levels of multiple receptors in the
      kidney, liver, and endothelium. Here, we characterize the self-association
      properties of the protein. PDZK1 can undergo modest homodimerization in vivo and
      in vitro through self-association involving its third PDZ domain. In addition,
      the tail of PDZK1 interacts in an intramolecular fashion with the first PDZ
      domain, but this interaction does not contribute to dimer formation. The
      interaction between the tail of PDZK1 and its first PDZ domain induces the
      protein to adopt a more compact conformation. A head-to-tail association has also
      been reported for EBP50/NHERF1, a two-PDZ domain member of the same scaffolding
      protein family as PDZK1, and shown to regulate binding of target proteins to the
      EBP50 PDZ domains. As opposed to EBP50, the association of PDZK1 with specific
      ligands for its PDZ domains is unaffected by the intramolecular association,
      establishing a different mode of interaction among these two members of the same
      scaffolding family. However, the tail of PDZK1 interacts with the PDZ domains of
      EBP50, and this interaction is negatively regulated by the intramolecular
      association of PDZK1. Thus, we have uncovered a regulated association between the
      two PDZ-containing scaffolding molecules, PDZK1 and EBP50.

PMID- 19173581
TI  - Bond angle distributions of carbon dioxide in the gas, supercritical, and solid
      phases.
AB  - Recent work has focused attention on possible shifts in the bond angle
      distribution of CO(2) as a consequence of intermolecular interactions in the
      supercritical phase. To investigate the temperature and phase dependence of the
      intramolecular structure of CO(2), we performed Feynman path integral Monte Carlo
      calculations based on a spectroscopically derived analytical potential, first
      principles molecular dynamics simulations using Kohn-Sham density functional
      theory, and Monte Carlo simulations employing empirical interaction potentials.
      On the basis of various distributions used to characterize the intramolecular
      structure, we conclude that the aggregation state has a negligible influence on
      the intramolecular structure, in particular we find that in the classical limit
      the distributions are remarkably similar for the ideal gas, supercritical, and
      solid phases when considered at the same temperature. In contrast, an increase in
      the temperature from 325 to 673 K or inclusion of nuclear quantum effects leads
      to a significant broadening of the distributions. With respect to the first C-O
      bond vector, the second bond vector most prefers a collinear arrangement.
      However, due to the Jacobian factor the maximum in the bond angle distribution at
      325 K is shifted to an angle of about 175.7 degrees in the classical limit or to
      173.0 degrees if nuclear quantum effects are included. Nevertheless, an analysis
      of the temperature dependence of the constant-volume heat capacity demonstrates
      that carbon dioxide should be viewed as a linear molecule.

PMID- 19173582
TI  - Cation-pi controlled solid-state photodimerization of 4-azachalcones.
AB  - We described a new approach for the solid-state photodimerization of alkenes in
      which the cation-pi interaction between a pyridinium and an aromatic ring serves
      as a powerful tool to control the alignment of alkenes in a crystal. The
      irradiation of 4-azachalcone (1a) gave the synHT dimer 2a in 49% yield, whereas
      the photolysis of 4'-methoxy-4-azachalcone (1b) afforded the synHH dimer 3b in
      67% yield. On the other hand, the photodimerization of 1a.HCl and 1b.HCl
      exclusively afforded the synHT dimers 2a and 2b, respectively, in quantitative
      yields. The structures of the produced dimers were clarified by X-ray
      crystallographic analyses. A comparison of the X-ray packing structures of 1a and
      1b with 1a.HCl and 1b.HCl clarified the significant differences between them. The
      separations of the two reactive double bonds of the HCl salts are much shorter
      than those of 1a and 1b, strongly suggesting the existence of an intermolecular
      cation-pi interaction in the pyridinium salts. These results are evidence of the
      significant effectiveness in the cation-pi controlled solid-state
      photodimerization on the stereoselective formation of cyclobutane dimers.

PMID- 19173584
TI  - Experimental evidence for water mediated electron transfer through bis-amino acid
      donor-bridge-acceptor oligomers.
AB  - This work compares the photoinduced unimolecular electron transfer rate constants
      for two different solute molecules (D-SSS-A and D-SRR-A) in water and DMSO
      solvents. The D-SSS-A solute has a cleft between the electron donor and acceptor
      units, which is able to contain a water molecule but is too small for DMSO. The
      rate constant for D-SSS-A in water is significantly higher than that for D-SRR-A,
      which lacks a cleft, and significantly higher for either solute in DMSO. The
      enhancement of the rate constant is explained by an electron tunneling pathway
      that involves water molecule(s).

PMID- 19173585
TI  - Theoretical investigation on structures, densities, detonation properties, and
      the pyrolysis mechanism of the derivatives of HNS.
AB  - The derivatives of 2,2',4,4',6,6'-hexanitrostilbene (HNS) are optimized to obtain
      their molecular geometries and electronic structures at the DFT-B3LYP/6-31G*
      level. Detonation properties are evaluated using the modified Kamlet-Jacobs
      equations based on the calculated densities and heats of formation. It is found
      that there are good linear relationships between the density, detonation
      velocity, detonation pressure, and number of nitro, amino, and hydroxy groups.
      The thermal stability and pyrolysis mechanism of the title compounds are
      investigated by calculating the bond dissociation energies at the unrestricted
      B3LYP/6-31G* level. For the nitro and amino derivatives of HNS, the C-NO(2) bond
      is a trigger bond during the thermolysis initiation process, while for hydroxy
      derivatives, it is started from the isomerization reaction of the hydrogen
      transfer in the O-H bond. According to the quantitative standard of energetics
      and stability, as high-energy density compounds, 2,2',3,3',4,4',5,6,6'
      nonanitrostilbene and 2,2',3,3',4,4',5,5',6,6'-decanitrostilbene essentially
      satisfy this requirement. In addition, we have discussed the effect of the nitro,
      amino, and hydroxy groups on the structure and properties.

PMID- 19173586
TI  - Experimental and theoretical characterization of adsorbed water on self-assembled
      monolayers: understanding the interaction of water with atmospherically relevant
      surfaces.
AB  - A combination of experiments and molecular dynamic (MD) simulations has been
      applied to elucidate the nature of water on organic self-assembled monolayers
      (SAMs) before and after oxidation. SAMs mimic organics adsorbed on environmental
      urban surfaces. Water on clean or SAM-coated borosilicate glass surfaces was
      measured at equilibrium as a function of relative humidity (RH), using
      transmission Fourier transform infrared (FTIR) spectroscopy at 1 atm and 22 +/- 1
      degrees C. The SAMs included C18 and C8 alkanes, as well as the C8 terminal
      alkene. Oxidation of the terminal alkene SAM was carried out with either KMnO(4)
      solution or gaseous O(3). The FTIR data showed at least two distinct peaks due to
      water on these surfaces, one at approximately 3200 cm(-1), which dominates at low
      RH (20%), and one at approximately 3400 cm(-1) at high RH (80%), which is similar
      to that in bulk liquid water. Temperature-programmed desorption (TPD) experiments
      showed that oxidation leads to more strongly adsorbed water. However, the amount
      of water in equilibrium with water vapor on the oxidized alkene was not
      significantly different from that on the unoxidized SAM, although there was a
      change in the relative intensities of the two contributing infrared peaks at 80%
      RH. MD simulations with hydrogen bond analysis suggest that molecules on the
      surface of small water clusters that dominate on SAM surfaces at low RH have
      fewer hydrogen bonds, while those in the interior of the clusters have three and
      four hydrogen bonds similar to bulk liquid water. Taken together, the
      experimental infrared data and MD simulations suggest a correlation between the
      relative intensities of the 3200 cm(-1)/3400 cm(-1) bands and the hydrogen
      bonding patterns of the water on the surface and in the interior of clusters on
      the SAM surfaces. These studies suggest that water clusters will be present even
      on hydrophobic surfaces in the atmosphere and hence are available to participate
      in heterogeneous chemistry. In addition, oxidation of organic coatings on
      atmospheric particles or surfaces in the boundary layer may not lead to enhanced
      water uptake as is often assumed.

PMID- 19173588
TI  - Nickel-63 microirradiators.
AB  - Here we report the fabrication of two types of microirradiators, consisting of a
      recessed disk and protruding wire with low-beta-energy radionuclide Ni-63
      electrodeposited onto a 25 microm diameter Pt wire. Ni-63 is constricted to a
      small surface area of the microelectrode; hence, this tool provides a means of
      delivery of localized, large dose density of beta radiation to the object but a
      minimal dose exposure to the user. The activity levels of Ni-63 emitted from the
      recessed disk and protruding wire are 0.25 and 1 Bq, respectively. The
      corresponding beta particles flux levels emitted from the recessed disk and
      protruding wire are 51 and 11 kBq/cm(2), respectively. These values, measured
      experimentally using liquid scintillation counting, fit very well the expected
      values of activity for each microirradiator, calculated considering the self
      absorption effect, typical for low-energy beta particles. In order to determine
      the optimal configuration the dose rates for varying distances from the object
      were calculated.

PMID- 19173589
TI  - Screening assay for metal-catalyzed oxidation inhibitors using liquid
      chromatography-mass spectrometry with an N-terminal beta-amyloid peptide.
AB  - Production of microregional catalytic reactive oxygen species (ROS) by metal
      binding amyloid-beta (Abeta) peptides mediates the neurotoxicity of Alzheimer's
      disease, and inhibitors of this activity may be of therapeutic value. No current
      analytical methods target specific ROS inhibitors produced by metal-binding
      peptides. We report a screening assay for metal-catalyzed oxidation (MCO)
      inhibitors based on liquid chromatography-mass spectrometry (LC-MS) with a model
      N-terminal Abeta peptide (Abeta(1-6)). When subjected to MCO by Cu(II)/ascorbic
      acid, singly and doubly charged Abeta(1-6) molecules were observed at m/z 729.2
      and 364.8 and m/z 685.3 and 343.3, respectively, corresponding to a decrease in
      mass of 45 and 89 Da compared with the model peptide. In contrast, H(2)O(2) did
      not modify the Abeta(1-6) peptide. Modified peptides were characterized by a
      specific MCO of Abeta(1-6), which contains both His and N-terminal Asp residues.
      LC-MS detection of the modified peptides allowed us to identify antioxidants that
      inhibit MCO of Abeta(1-6). MCO of the model peptide was inhibited by curcumin,
      but not dibutylhydroxytoluene, carotene, tocopherol, estradiol or nicotine,
      revealing a clear difference between curcumin and other antioxidants. This novel
      assay may allow for the identification of antioxidants that protect against MCO
      of peptides and proteins related to degenerative diseases.

PMID- 19173594
TI  - Essential role of c-Cbl in amphiregulin-induced recycling and signaling of the
      endogenous epidermal growth factor receptor.
AB  - The intracellular processing of the epidermal growth factor receptor (EGFR)
      induced by epidermal growth factor (EGF) and transforming growth factor-alpha
      (TGF-alpha) has been studied meticulously, with the former resulting in EGFR
      degradation and the latter in EGFR recycling to the plasma membrane. However,
      little is known about how other EGF family growth factors affect the trafficking
      of the EGFR. Additionally, although both EGF and TGF-alpha have been shown to
      effectively induce initial c-Cbl (ubiquitin ligase)-mediated ubiquitination of
      the EGFR, limited information is available regarding the role of c-Cblin the
      trafficking and signaling of recycling EGFR. Thus, in this study, we investigated
      the roles of c-Cblin endogenous EGFR trafficking and signaling after stimulation
      with amphiregulin (AR). We demonstrated that a physiological concentration of AR
      induced recycling of the endogenous EGFR to the plasma membrane, which correlated
      closely with transient association of the EGFR with c-Cbl and transient EGFR
      ubiquitination. Most importantly, we used c-Cbl small interfering RNA (siRNA)
      duplexes and ac-Cbl dominant negative mutant to show that c-Cbl is critical for
      the efficient transition of the EGFR from early endosomes to a recycling pathway
      and that c-Cbl regulates the duration of extracellular signal regulated kinase
      1/2 mitogen-activated protein kinase (ERK1/2 MAPK) phosphorylation. These data
      support novel functions of c-Cbl in mediating recycling of EGF receptors to the
      plasma membrane, as well as in mediating the duration of activation (transient vs
      sustained) of ERK1/2 MAPK phosphorylation.

PMID- 19173596
TI  - Relationship between hydrophobic interactions and secondary structure stability
      for Trpzip beta-hairpin peptides.
AB  - The temperature-induced beta-hairpin stabilities of selected mutations of the
      Trpzip1 peptide, SWTWEGNKWTWK (WWWW), have been investigated by electronic
      circular dichroism (CD), Raman, and FT-IR spectroscopies. The tryptophan (Trp)
      residues in the original Trpzip1 sequence were systematically substituted with
      tyrosine (Tyr) in different positions to test the impact of Trp interactions on
      the beta-hairpin structure and stability. The CD intensity at approximately 228
      nm, which arises from Trp-Trp interactions (tertiary structure), and the amide I'
      IR absorbance at approximately 1635 cm(-1) (secondary structure) have been
      measured over a range of temperatures to investigate the impact of Tyr
      substitution on beta-hairpin thermal stability in Trpzip peptides. Mutation from
      Trp to Tyr in the Trpzip1 sequence reduces the extent of beta-hairpin structure
      and monotonically decreases the beta-hairpin stability of Trpzip1 mutant peptides
      with an increasing number of Tyr substitutions. Substituted Trpzip peptides with
      just one pair of Trp-Trp interactions close to either the terminal residues
      (WYYW) or the turn (YWWY) have similar stabilities. Comparison of conformational
      transitions monitored by CD and IR reveals them to have multistate behavior in
      which the temperature-induced disruption of the Trp-Trp interaction (tertiary
      structure) occurs at a lower temperature than the unfolding of the secondary
      structure.

PMID- 19173595
TI  - Differential accessibilities of dibasic prohormone processing sites of
      proenkephalin to the aqueous environment revealed by H-D exchange mass
      spectrometry.
AB  - Proenkephalin (PE) is a prohormone containing dibasic sites that are cleaved by
      proteases to generate peptide neurotransmitters and hormones. Little is known
      about the conformational features of such protease cleavage sites within
      prohormone substrates. Therefore, the goal of this study was to investigate the
      relative accessibilities of multiple dibasic processing sites of PE by peptide
      amide hydrogen-deuterium exchange mass spectrometry (DXMS). DXMS demonstrated
      differences in the relative accessibilities of the KR, KK, and RR cleavage sites
      of PE to the aqueous environment. DXMS assesses relative rates of exchange of
      hydrogens of the polypeptide backbone of PE with deuterium atoms from D(2)O
      (heavy water) in solvent. Analyses of peptides spanning each of the 12 dibasic PE
      cleavage sites illustrated differences in H-D exchange rates that reflect
      relative solvent accessibility. The mid-domain cleavage sites (dibasic sites 4-8)
      exhibited greater accessibility to the aqueous solvent compared to regions of the
      NH(2) and COOH domains (dibasic sites 2, 3, and 9-11, respectively). The NH(2)-
      and COOH-terminal domains both exhibited relatively high H-D exchange rates. The
      hydrogen exchange rate profile of PE, as well as its circular dichroism (CD)
      features for secondary structure, was modified in trifluoroethanol, an organic
      solvent that represents a more hydrophobic environment. These findings suggest
      that the dibasic protease cleavage sites of the PE prohormone with differences in
      accessibility to the aqueous environment undergo proteolytic processing to
      generate active neuropeptides for cell-cell communication in neuroendocrine
      systems.

PMID- 19173597
TI  - From D-glucose to enantiomerically pure cycloctanoses. The glycosidase inhibitory
      capacity of medium-ring carbasugars.
AB  - Exhaustive dihydroxylation of the pair of cyclooctadienols consisting of 4 and 5,
      which are available in enantiomerically pure form from d-glucose, resulted in the
      formation of two diastereomeric tetraols in each case. The difference in polarity
      of the 6/7 and 8/9 pairs facilitated their chromatographic separation. Ensuing
      acetylation and PMB deprotection allowed for the assignment of relative (and
      ultimately absolute) stereochemistry to the resulting monohydric alcohols on the
      basis of J(HH) analysis of their (1)H NMR spectra. The highly functionalized
      exomethylenecyclooctanes 14-17, which were derived by periodinane oxidation and
      Wittig olefination, were further elaborated by hydroboration and global
      deprotection. The eight members of the cyclooctanose family of carbasugars and
      their precursor intermediates consistently showed patterns of J(HH) values in
      line with the contiguous stereochemical relationships. Also assayed was their
      specific inhibitory behavior toward glycosidases.

PMID- 19173598
TI  - Phosphine-mediated [3+2] cycloaddition reactions of ethyl 5,5-diarylpenta-2,3,4
      trienoates with arylmethylidenemalononitriles and N-tosylimines.
AB  - Ethyl 5,5-diarylpenta-2,3,4-trienoates were synthesized and utilized in the
      phosphine-mediated [3+2] cycloaddition reactions with
      arylmethylidenemalononitriles and N-tosylimines in the presence of
      tributylphosphine. These reactions provide an easy access to a variety of novel
      polysubstituted cyclopentenes or pyrrolidines in good to excellent yields under
      mild conditions.

PMID- 19173600
TI  - Hexadentate bispidine derivatives as versatile bifunctional chelate agents for
      copper(II) radioisotopes.
AB  - The preparation and use of bispidine derivatives (3,7-diazabicyclo[3.3.1]nonane)
      as chelate ligands for radioactive copper isotopes for diagnosis (64Cu) or
      therapy (67Cu) are reported. Starting from the hexadentate bispidine-based
      bis(amine)tetrakis(pyridine) ligand 1 with a keto and two ester substituents, the
      corresponding mono-ol 2 and two dicarboxylic acid derivatives 3 and 5 have been
      synthesized. A range of techniques, including single-crystal X-ray structure
      analysis, UV/vis spectroscopy, cyclic voltammetry, thin-layer- (TLC), and high
      performance liquid chromatography (HPLC), have been used to characterize the
      structure and stability of the copper(II)-bispidine complexes. A rapid formation
      (within 1 min) of stable copper(II)-bispidine complexes under mild conditions
      (ambient temperature, aqueous solution) has been observed. Challenge experiments
      of these complexes in the presence of a high excess of competing ligands, such as
      glutathione, cyclam, or superoxide dismutase (SOD), as well as in rat plasma,
      gave no evidence of demetalation or transchelation. The bifunctional bispidine
      derivative 5 can be readily functionalized with biologically active molecules at
      the pendant carboxylate groups. The coupling of a bombesin analogue betahomo-Glu
      betaAla-betaAla-[Cha(13),Nle(14)]BBN(7-14), by condensation of a carboxylate of
      the bispidine backbone with the N-terminus of the peptide produced the
      bifunctional ligand 6. The radiocopper(II) complex of this bombesin-bispidine
      conjugate has a considerable hydrophilicity (log D(o/w) < -2.4), and this leads
      to a very fast blood clearance (blood: 0.28 +/- 0.02 SUV, 1 h p.i.), low liver
      tissue accumulation (liver: 1.20 +/- 0.27 SUV, 1 h p.i.), and rapid renal-urinary
      excretion (kidneys: 6.06 +/- 2.96 SUV, 1 h p.i.) as shown by biodistribution
      studies of 64Cu-6 in Wistar rats. Preliminary in vivo studies of 64Cu-6 in NMRI
      nu/nu mice, bearing the human prostate tumor PC-3 showed an accumulation of the
      conjugate in the tumor (2.25 +/- 0.13 SUV, 12.5 min p.i.; 0.94 +/- 0.05 SUV, 55
      min p.i.) and allowed a clear visualization of the gastrin-releasing peptide
      receptor distribution by positron emission tomography (PET).

PMID- 19173601
TI  - Olive oil qualitative parameters after orchard irrigation with saline water.
AB  - The effect of irrigation with saline water on oil quality was studied in the two
      olive ( Olea europaea L.) cultivars Koroneiki and Mastoidis, which are the main
      varieties grown extensively on the island of Crete. Plants (5 years old) were
      grown outdoors in containers, filled with freely drained light soil. Four
      treatments were applied, differing in the NaCl added to the irrigation water as
      follows: 0 (control) 50, 100, and 150 mM NaCl. Drip irrigation was applied
      regularly, during the dry season (from April to October). Plants in all
      treatments were irrigated when the soil-water potential reached -40 kPa at a
      depth of 30 cm. Data showed that increased NaCl levels in irrigation water
      resulted in a decrease in oil content in the fruits and an increase in total
      phenols and their secoiridoid derivatives in olive oils from harvested fruits.
      Furthermore, changes also took place in the composition of fatty acids and
      triacylglycerol molecular species. The extent of alterations was different for
      the two varieties and greater in cv. Koroneiki. This fitted with agronomic
      evidence that cv. Koroneiki is less saline-tolerant than cv. Mastoidis.

PMID- 19173602
TI  - Transcriptome analysis of potato tubers--effects of different agricultural
      practices.
AB  - The use of profiling techniques such as transcriptomics, proteomics, and
      metabolomics has been proposed to improve the detection of side effects of plant
      breeding processes. This paper describes the construction of a food safety
      oriented potato cDNA microarray (FSPM). Microarray analysis was performed on a
      well-defined set of tuber samples of two different potato varieties, grown under
      different, well-recorded environmental conditions. Data were analyzed to assess
      the potential of transcriptomics to detect differences in gene expression due to
      genetic differences or environmental conditions. The most pronounced differences
      were found between the varieties Sante and Lady Balfour, whereas differences due
      to growth conditions were less significant. Transcriptomics results were
      confirmed by quantitative PCR. Furthermore, the bandwidth of natural variation of
      gene expression was explored to facilitate biological and/or toxicological
      evaluation in future assessments.

PMID- 19173603
TI  - Novel key aroma components of galbanum oil.
AB  - Galbanum oil is composed of monoterpenes in large amounts and pyrazines in small
      amounts. Although the monoterpenes are the main components of galbanum oil, they
      hardly contribute to the distinct galbanum aroma. The scanty amounts of
      pyrazines, in contrast, contribute significantly to the aroma. Considering the
      complexity and potency of the odor, the essential oil was assumed to contain so
      far not identified compounds with high odor contribution. By the gas
      chromatography-mass spectrometry-olfactometry (GC-MS-O) analysis of galbanum oil,
      fruity-green-balsamic notes were detected at two different retention times. The
      mass spectra (MS) of the newly discovered notes were elucidated by conducting
      multidimensional (MD) GC-MS-O. By analyzing the MS data, six chemical structures
      were proposed: (6E/Z,8E)-undeca-6,8,10-trien-2-one, (6E/Z,8E)-undeca-6,8,10-trien
      3-one, and (6E/Z,8E)-undeca-6,8,10-trien-4-one. The compounds were then
      synthesized in an attempt to match the MS, retention indices (RI), and odor
      qualities. The MD-GC-MS-O analyses of the candidate compounds led to the
      identification of the novel key aroma compounds (6Z,8E)-undeca-6,8,10-trien-3-one
      and (6Z,8E)-undeca-6,8,10-trien-4-one in galbanum oil.

PMID- 19173604
TI  - Electrically assisted extraction of soluble matter from chardonnay grape skins
      for polyphenol recovery.
AB  - The objective of this study was to investigate the effects of pulsed electric
      field (PEF) and high-voltage electrical discharges (HVED) application on the
      efficiency of aqueous extraction of total soluble matter and polyphenols from
      grape skins ( Vitis vinifera L.) at different temperatures within 20-60 degrees
      C. The highest level of polyphenol concentration C was reached after about 60 min
      of extraction for HVED treatment: C(HVED) = 21.4 +/- 0.8 micromol of gallic acid
      equivalent (GAE)/g of dry matter (DM). Almost the same level of C was reached
      after 180 min of extraction for the PEF-treated skins. These levels exceeded the
      value C = 19.1 +/- 0.5 micromol of GAE/g of DM for the untreated samples. The
      difference between degrees Brix values for HVED-treated and untreated systems
      decreased with temperature increase (from 40 to 60 degrees C), but a large
      difference in the total amount of polyphenols was observed for HVED-treated and
      untreated systems. The activation energies were W(u) = 31.3 +/- 3.7 kJ/mol and
      W(PEF) = 28.9 +/- 5.5 kJ/mol for untreated and PEF-treated systems, respectively.

PMID- 19173605
TI  - Extra binding region induced by non-zinc chelating inhibitors into the S1'
      subsite of matrix metalloproteinase 8 (MMP-8).
AB  - The mode of binding and the activity of the first two non-zinc chelating, potent,
      and selective inhibitors of human neutrophil collagenase are reported. The
      crystal structures of the catalytic domain of MMP-8, respectively complexed with
      each inhibitor, reveals that both ligands are deeply inserted into the primary
      specificity subsite S(1)', where they induce a similar conformational change of
      the surrounding loop that is endowed with the main specificity determinants of
      MMPs. Accord to this rearrangement, both inhibitors remove the floor of the
      pocket formed by the Y227 side-chain, rendering available an extra binding region
      never explored before. The present data show that potent and more selective
      inhibitors can be obtained by developing ligands able to interact with the
      selectivity regions of the enzyme rather than with the catalytic zinc ion, which
      is the common feature of all MMP members.

PMID- 19173609
TI  - Synthesis of 2'-C-beta-methyl-2'-deoxyguanosine.
AB  - We describe two approaches for the synthesis of 2'-C-beta-methyl-2'
      deoxyguanosine (3) via 2'-radical deoxygenation. One approach starts from 1,3,5
      tri-O-benzoyl-alpha-d-ribofuranose (6) and gives 3 in 11 steps with 9.7% overall
      yield. The second approach starts from guanosine and gives 3 in 8 steps with 23%
      overall yield.

PMID- 19173610
TI  - Pd-catalyzed C-C cross-coupling reactions within a thermoresponsive and pH
      responsive and chelating polymeric hydrogel.
AB  - A porous, thermoresponsive and pH-responsive, and chelating hydrogel of poly(N
      isopropylacrylamide)-co-poly[2-methacrylic acid 3-(bis-carboxymethylamino)-2
      hydroxypropyl ester] (PNIPAM-co-PMACHE) is proposed as both a reaction medium and
      the Pd catalyst support for organic synthesis. Organic synthesis within the
      PNIPAM-co-PMACHE hydrogel has three merits. First, organic reactions such as
      Suzuki and Heck reactions within the hydrogel can be accelerated due to the
      enriched Pd catalyst and reactants within the hydrogel by the reversible
      deswelling/swelling. Second, organic synthesis within the PNIPAM-co-PMACHE
      hydrogel, which holds about approximately 300 times of water and is similar to
      the environmentally benign reaction medium of water, can be performed efficiently
      without surfactant or cosolvent being added. Third, the PNIPAM-co-PMACHE hydrogel
      itself and the therein-immobilized Pd catalyst can be easily recycled since the
      hydrogel/Pd composite can reversibly swell/deswell.

PMID- 19173611
TI  - Selectivity in ligand recognition of G-quadruplex loops.
AB  - A series of disubstituted acridine ligands have been cocrystallized with a
      bimolecular DNA G-quadruplex. The ligands have a range of cyclic amino end groups
      of varying size. The crystal structures show that the diagonal loop in this
      quadruplex results in a large cavity for these groups, in contrast to the steric
      constraints imposed by propeller loops in human telomeric quadruplexes. We
      conclude that the nature of the loop has a significant influence on ligand
      selectivity for particular quadruplex folds.

PMID- 19173612
TI  - Temporal analysis of neural differentiation using quantitative proteomics.
AB  - The ability to derive neural progenitors, differentiated neurons and glial cells
      from human embryonic stem cells (hESCs) with high efficiency holds promise for a
      number of clinical applications. However, investigating the temporal events is
      crucial for defining the underlying mechanisms that drive this process of
      differentiation along different lineages. We carried out quantitative proteomic
      profiling using a multiplexed approach capable of analyzing eight different
      samples simultaneously to monitor the temporal dynamics of protein abundance as
      human embryonic stem cells differentiate into motor neurons or astrocytes. With
      this approach, a catalog of approximately 1200 proteins along with their relative
      quantitative expression patterns was generated. The differential expression of
      the large majority of these proteins has not previously been reported or studied
      in the context of neural differentiation. As expected, two of the widely used
      markers of pluripotency, alkaline phosphatase (ALPL) and LIN28, were found to be
      downregulated during differentiation, while S-100 and tenascin C were upregulated
      in astrocytes. Neurofilament 3 protein, doublecortin and CAM kinase-like 1 and
      nestin proteins were upregulated during motor neuron differentiation. We
      identified a number of proteins whose expression was largely confined to specific
      cell types, embryonic stem cells, embryoid bodies and differentiating motor
      neurons. For example, glycogen phosphorylase (PYGL) and fatty acid binding
      protein 5 (FABP5) were enriched in ESCs, while beta spectrin (SPTBN5) was highly
      expressed in embryoid bodies. Karyopherin, heat shock 27 kDa protein 1 and
      cellular retinoic acid binding protein 2 (CRABP2) were upregulated in
      differentiating motor neurons but were downregulated in mature motor neurons. We
      validated some of the novel markers of the differentiation process using
      immunoblotting and immunocytochemical labeling. To our knowledge, this is the
      first large-scale temporal proteomic profiling of human stem cell differentiation
      into neural cell types highlighting proteins with limited or undefined roles in
      neural fate.

PMID- 19173613
TI  - Quantification of isotopically overlapping deamidated and 18o-labeled peptides
      using isotopic envelope mixture modeling.
AB  - A robust peptide quantification method was developed where overlapping peptide
      isotopic distributions were fit with predicted peptide isotopic envelope mixture
      models (IEMMs). Application to two difficult quantitative problems was
      demonstrated. The first was the quantification of deamidation, where masses of
      isotopic peaks differ by 1 Da, and the second was (18)O labeling, where the
      isotopic peaks are shifted 2 and 4 Da. In both cases, peptide quantification
      cannot be performed by simple integration of extracted ion chromatograms, because
      the isotopic envelopes of mass-shifted peptides are normally not resolved. To
      test the methodology for quantification of deamidation, several synthetic
      peptides and their corresponding deamidated forms were mixed at various ratios
      (1:0, 1:2, 2:1, 4:1, 10:1, and 20:1) and analyzed using the IEMM method,
      resulting in a high correlation (R(2) = 0.96) between measured and known
      percentages of deamidation. The IEMM method was then incorporated into a workflow
      for deamidation quantification in a large-scale proteomics experiment. A series
      of normal (3 day, 2 year, 35 year, and 70 year) and cataractous (93 year) human
      lenses were analyzed using two-dimensional liquid chromatography tandem mass
      spectrometry, and deamidation quantities of several gammaS-crystallin peptides
      ([N14-Q16], N53, [Q63-Q70], and N143) were determined. Two peptides (N53 and [Q63
      Q70]) had more extensive deamidation in the water-insoluble portions of normal
      lens samples, and deamidation at N143 was more extensive in the 93 year water
      insoluble cataractous sample. The utility of the technique for analysis of (18)O
      labeled peptides was examined using mixtures of labeled BSA peptides in known
      (16)O/(18)O ratios (10:1, 4:1, 1:1, 1:4, and 1:10). The methodology allowed for
      accurate measurements of ratios of (16)O/(18)O peptides over the wide range of
      relative abundances.

PMID- 19173614
TI  - Field-ion microscopy of quantum oscillations of linear carbon atomic chains.
AB  - Field ion microscopic imaging of monatomic carbon chains near the ground quantum
      states and the visualization of their two-dimensional wave functions were
      demonstrated. Quantum motions with the frequency proportional to the electric
      field are detected and analyzed with subangstrom lateral resolution. Electric
      fields above 10(10) V/m can be used for control of a transverse vibration mode of
      atomic chains in the terahertz spectral range.

PMID- 19173616
TI  - A new artificial beta-sheet that dimerizes through parallel beta-sheet
      interactions.
AB  - This paper introduces a chemical model of a beta-sheet that dimerizes through
      parallel beta-sheet interactions in CDCl(3) solution. The model consists of two C
      terminally linked dipeptides connected to a molecular template. (1)H NMR studies
      establish the beta-sheet folding and dimerization of the model system. This
      system corroborates that linking two peptide strands and blocking one edge of the
      assembly creates soluble, easy-to-study systems that participate in the types of
      interactions that occur widely in peptide and protein aggregates.

PMID- 19173617
TI  - A biomimetic electrocatalytic system for the atom-economical chemoselective
      synthesis of secondary amines.
AB  - A facile one-pot oxidation-imine formation-reduction route to secondary amines
      can be achieved electrolytically from primary amines. This atom-economical 1(ox)
      mediated sequence, leaving ammonia as the sole byproduct, allows the rapid
      chemoselective synthesis of secondary amines, at both ambient temperature and
      pressure.

PMID- 19173618
TI  - PIFA-mediated oxidative cyclization of 1-carbamoyl-1-oximylcycloalkanes:
      synthesis of spiro-fused pyrazolin-5-one N-oxides.
AB  - A convenient and efficient synthesis of spiro-fused pyrazolin-5-one N-oxides
      starting from readily available 1-carbamoyl-1-oximylcycloalkanes is developed.
      This general protocol features a novel and facile way for access to the five
      membered azaheterocycles by formation of a new N-N single bond. The key
      cyclization step utilizes the formation of an N-oxonitrenium intermediate,
      mediated by the hypervalent iodine reagent PIFA, and its subsequent
      intramolecular trapping by the amide moiety under rather mild experimental
      conditions.

PMID- 19173619
TI  - Electrochemical DNA biosensor based on the proximity-dependent surface
      hybridization assay.
AB  - This paper describes a novel electrochemical DNA (E-DNA) biosensor for simple,
      rapid, and specific detection of nucleic acids based on the proximity-dependent
      surface hybridization assay. This E-DNA biosensor was constructed by self
      assembly of a 3' short thiolated capture probe on the gold electrode. DNA
      detection was realized by outputting a remarkable redox current of the 5'
      ferrocene (Fc) tail labeled probe. When the target DNA was introduced into the
      system, it was complementary to the 5' Fc labeled probe at the one-half-segment
      and complementary to the 3' short thiolated capture probe at the other half
      segment, resulting in forming a stable duplex complex. As a result, the Fc probe
      was proximate to the electrode surface, and the Faradaic current was observed.
      This E-DNA biosensor was proved to have a low detection limit (1 fM) and a wide
      dynamic range (from 1 fM to 1 nM) due to the stable hybridization mode. In
      addition, the sensing system could discriminate the complementary sequence from
      mismatch sequences, with high sensitivity, stability, and reusability.

PMID- 19173620
TI  - Minor groove binding compounds that jump a gc base pair and bind to adjacent AT
      base pair sites.
AB  - Most A/T specific heterocyclic diamidine derivatives need at least four A/T base
      pairs for tight binding to the DNA minor groove. Addition of a GC base pair to
      A/T sequences typically causes a large decrease in binding constant. The ability
      to target biologically important sequences of DNA could be significantly
      increased if compounds that could recognize A/T sites with an intervening GC base
      pair could be designed. The kinetoplast DNA sequence of parasitic microorganisms,
      for example, contains numerous three A/T binding sites that are separated by a
      single G. A series of compounds were prepared to target the AAAGTTT sequence as a
      model system for discovery of "G-jumpers". The new synthetic compounds have two
      aromatic-amidine groups for A/T recognition, and these are connected through an
      oxy-methylene linker to cross the GC. CD experiments indicated a minor groove
      binding mode, as expected, for these compounds. T(max), surface plasmon
      resonance, and isothermal titration calorimetry experiments revealed 1:1 binding
      to the AAAGTTT sequence with an affinity that depends on compound structure.
      Benzimidazole derivatives gave the strongest binding and had generally good
      solution properties. The binding affinities to the classical AATT sequence were
      similar to that for AAAGTTT for these extended compounds, but binding was weaker
      to the AAAGCTTT sequence with two intervening GC base pairs. Binding to both
      AAAGTTT and AATT was enthalpy driven for strong binding benzimidazole
      derivatives.

PMID- 19173621
TI  - Dietary derived sesquiterpenes from Phyllodesmium lizardensis.
AB  - The recently discovered new aeolidean species Phyllodesmium lizardensis
      Burghardt, Schrodl and Wagele, 2008 was investigated concerning its secondary
      metabolite profile. P. lizardensis so far has only been found on Lizard Island.
      Analysis of P. lizardensis led to the isolation of the new sesquiterpenes (+)
      3beta-hydroxy-alpha-muurolene (1) and (+)-3beta-acetoxy-alpha-muurolene (2). GC
      MS analysis of the host coral, identified as Heteroxenia sp., also showed the
      presence of compounds 1 and 2, whereas a sympatric Xenia species lacks these
      products. These results indicate that P. lizardensis specifically sequesters
      these compounds from Heteroxenia sp.

PMID- 19173627
TI  - Continuous alloy-composition spatial grading and superbroad wavelength-tunable
      nanowire lasers on a single chip.
AB  - By controlling local substrate temperature in a chemical vapor deposition system,
      we have successfully achieved spatial composition grading covering the complete
      composition range of ternary alloy CdSSe nanowires on a single substrate of 1.2
      cm in length. Spatial photoluminescence scan along the substrate length shows
      peak wavelength changes continuously from approximately 500 to approximately 700
      nm. Furthermore, we show that under strong optical pumping, every spot along the
      substrate length displays lasing behavior. Thus our nanowire chip provides a
      spatially continuously tunable laser with a superbroad wavelength tuning range,
      unmatched by any other available semiconductor-based technology.

PMID- 19173628
TI  - Piezoresistive InGaAs/GaAs nanosprings with metal connectors.
AB  - This paper presents the fabrication, assembly, and characterization of
      piezoresistive nanosprings for creating nanoelectromechanical systems. The
      fabrication process is based on conventional microfabrication techniques to
      create a planar pattern in a 27nm thick, n-type InGaAs/GaAs bilayer that self
      forms into three-dimensional structures during a wet etch release. As the
      nanosprings have lower doped thin and flexible layers, small metal pads have been
      attached to both sides for achieving stable ohmic contact with electrodes.
      Nanorobotic manipulation is applied to assemble the nanosprings between
      electrodes using electron-beam-induced deposition inside a scanning electron
      microscope, and the bridged nanosprings were then characterized for
      electromechanical properties. With their strong piezoresistive response, low
      stiffness, large-displacement capability, and excellent fatigue resistance, they
      are well-suited to function as sensing elements in high-resolution, large-range
      electromechanical sensors.

PMID- 19173629
TI  - One-pot high-throughput synthesis of beta-turn cyclic peptidomimetics via
      "volatilizable" supports.
AB  - A promising method for the high-throughput synthesis of linear C
      hydroxyalkylamido peptidomimetics and beta-turn cyclic peptidomimetics via
      "volatilizable" aminoalkyl functionalized silica gels is presented. Boc amino
      acids and carboxylic acids were coupled on functionalized aminoalkyl silica gels
      using a standard DIC/HOBt coupling protocol. After peptide synthesis, the resin
      bound peptide was cleaved using a two-step process to obtain the linear C
      hydroxyalkylamido peptidomimetics. Beta-turn cyclic peptidomimetics were
      generated by intramolecular S(N)Ar cyclization in an aqueous solution. Both the
      linear and the cyclic peptidomimetics were obtained with good to excellent yields
      and purities through a "one-pot" reaction.

PMID- 19173632
TI  - Bishydrazide derivatives of isoindoline as simple anion receptors.
AB  - Isoindoline has been investigated as a scaffold for the construction of anion
      receptors. A family of bishydrazide derivatives of isoindoline has been
      synthesized, and the anion-binding properties of these receptors were
      investigated both in solution and in the solid state. Enhanced affinity toward
      halides has been observed for isoindoline-based ligands compared to analogous
      pyrroledicarboxyamides. However, in the case of highly basic anions, the anion
      binding is accompanied by partial deprotonation of the receptors, which also
      leads to the color changes of ligands' solutions.

PMID- 19173633
TI  - High-rate solar photocatalytic conversion of CO2 and water vapor to hydrocarbon
      fuels.
AB  - Efficient solar conversion of carbon dioxide and water vapor to methane and other
      hydrocarbons is achieved using nitrogen-doped titania nanotube arrays, with a
      wall thickness low enough to facilitate effective carrier transfer to the
      adsorbing species, surface-loaded with nanodimensional islands of cocatalysts
      platinum and/or copper. All experiments are conducted in outdoor sunlight at
      University Park, PA. Intermediate reaction products, hydrogen and carbon
      monoxide, are also detected with their relative concentrations underlying
      hydrocarbon production rates and dependent upon the nature of the cocatalysts on
      the nanotube array surface. Using outdoor global AM 1.5 sunlight, 100 mW/cm(2), a
      hydrocarbon production rate of 111 ppm cm(-2) h(-1), or approximately 160
      microL/(g h), is obtained when the nanotube array samples are loaded with both Cu
      and Pt nanoparticles. This rate of CO(2) to hydrocarbon production obtained under
      outdoor sunlight is at least 20 times higher than previous published reports,
      which were conducted under laboratory conditions using UV illumination.

PMID- 19173634
TI  - Revisiting magnesium chelation by teichoic acid with phosphorus solid-state NMR
      and theoretical calculations.
AB  - Teichoic acids are essential components of the Gram-positive bacterial cell wall.
      One of their many functions is metal binding, a vital process for bacterial
      growth. With the combination of phosphorus-31 solid-state NMR spectroscopy and
      theoretical calculations using density functional theory (DFT), we have
      determined that the binding mode between teichoic acids and magnesium involves
      bidentate coordination by the phosphate groups of teichoic acid. Measurement of
      chemical shift anisotropy tensors gave a reduced anisotropy (delta) of 49.25 ppm
      and an asymmetry (eta) of 0.7. DFT calculations with diglycerol phosphate and
      triglycerol diphosphate model compounds were completed with Mg(2+) in anhydrous
      as well as partially hydrated bidentate and fully hydrated monodentate,
      bidentate, and bridging binding modes. (31)P CSA tensors were calculated from the
      energy-minimized model compounds using the combined DFT and GIAO methods,
      resulting in dramatically different tensor values for each binding mode. The
      anhydrous bidentate chelation mode was found to be a good approximation of the
      experimental data, an observation that alters the current monodentate paradigm
      for metal chelation by teichoic acids.

PMID- 19173635
TI  - Orientational ordering and low-temperature libration in the rotor-stator
      cocrystals of fullerenes and cubane.
AB  - Cocrystals of cubane and fullerenes, C60-cubane and C70-cubane, show distinct
      rotational ordering transitions. We studied the corresponding structural changes
      with temperature-dependent X-ray diffraction and the thermodynamics of the phase
      transitions with adiabatic microcalorimetry and differential scanning
      calorimetry. C60-cubane has one phase transition around 130 K from a high
      temperature fcc phase with freely rotating C60 to a low-temperature orthorombic
      phase in which the fullerene rotation is frozen. The corresponding enthalpy
      change is approximately 1170 J/mol, and the entropy change is 9.6 J/(mol K). C70
      cubane has two phase transitions. Around 380 K, the high-temperature fcc phase
      with freely rotating C70 transforms into a bct phase in which the C70 rotates
      uniaxially around an axis that precesses around the c direction with a full
      opening angle of 40 degree. Around 170 K, the uniaxial rotation also freezes out,
      with an accompanying structural transition to monoclinic and enthalpy and entropy
      changes of 620 J/mol and 8.7 J/(mol K), respectively. The low-temperature
      specific heat was analyzed in terms of the Debye-Einstein model to estimate the
      librational energies of the fullerenes and Debye temperatures. We found very
      similar values for the two cocrystals, approximately Elib = 2.2 meV and TDebye =
      23 K. For reference, we also measured the specific heats of pure C60 and C70 and
      found Elib = 2.96 meV and TDebye = 32 K for C60 and Elib = 1.9 meV and TDebye =
      20 K for C70.

PMID- 19173637
TI  - Graphene-based composite thin films for electronics.
AB  - The electrical properties of solution-processed composite thin films consisting
      of functionalized graphene sheets (FGS) as the filler and polystyrene (PS) as the
      host material are described. We demonstrate that transistors from graphene-based
      composite thin films exhibit ambipolar field effect characteristics, suggesting
      transport via percolation among FGS in the insulating PS matrix. Device
      characteristics as a function of the FGS size are also reported. The results
      indicate that devices fabricated using the largest size FGS yield the highest
      mobility values. This simple and scaleable fabrication scheme based on a
      commodity plastic could be useful for low-cost, macro-scale electronics.

PMID- 19173638
TI  - Structural analysis of [ChCl](m)[ZnCl(2)](n) ionic liquid by X-ray absorption
      fine structure spectroscopy.
AB  - The components and structures of ionic liquid ChCl-ZnCl(2) in different
      ChCl:ZnCl(2) ratios were investigated using XAFS (X-ray absorption fine
      structure) technique. The average coordination number and distance of Zn species
      at different x(ZnCl(2)) (mole fraction of ZnCl(2) when synthesizing) were
      calculated. It is shown that x(ZnCl(2)) has a regular influence on the
      coordination number of Zn species, due to the change of anion forms and
      structures in the ChCl-ZnCl(2) ionic liquid. The possible forms and structures of
      Zn species in the ionic liquids were analyzed according to the coordination
      number. XAFS and DSC (differential scanning calorimetry) analysis imply that
      besides ZnCl(3)(-) and Zn(2)Cl(5)(-) anions, the Cl-Zn-Cl ion pair is a main
      species in the ionic liquid at higher x(ZnCl(2)). This newly discovered Zn
      species has substantial influence on the properties of the ionic liquid. From the
      analysis of the coordination numbers and coordination distance, a new mechanism
      of interactions between Ch(+) cation and Cl-Zn-Cl ion pairs or Cl(-) is proposed.

PMID- 19173640
TI  - Implementation of a DFT-based method for the calculation of the Zeeman g-tensor
      in periodic systems with the use of numerical and Slater-type atomic orbitals.
AB  - The Zeeman g-tensor parameterizes the interaction of an effective electronic spin
      with the homogeneous external magnetic field in the electron paramagnetic
      resonance (EPR) experiment. In this article, we describe a Kohn-Sham DFT (KS DFT)
      based implementation of the g-tensor for periodic systems. Our implementation can
      be used, for example, for the first-principles calculation of a g-tensor of
      paramagnetic defects in solids. Our approach is based on the method of Van Lenthe
      et al. in which the spin-orbital coupling is taken into account variationally.
      The method is implemented in the BAND program, a KS DFT implementation for
      periodic systems. The Bloch states are expanded in the basis of numerical and
      Slater-type atomic orbitals (NAOs/STOs). Our implementation does not rely on the
      frozen core approximation tacitly assumed in the pseudopotential schemes. The
      implementation is validated by calculating the g-tensor for small molecules as
      well as for paramagnetic defects in solids. In particular, we consider ozonide
      and hydrogen cyanide anion radicals in a KCl host crystal lattice.

PMID- 19173643
TI  - MOLCAS 7.2.

PMID- 19173644
TI  - Effects of lattice expansion on the reactivity of a one-dimensional oxide.
AB  - By means of scanning tunneling microscopy (STM) and density functional theory
      (DFT) calculations, we characterize at the single-atom level the mechanism of the
      water formation reaction on the (10 x 2)-O/Rh(110) surface, a prototype of a one
      dimensional (1D) oxide where the lattice expansion and the segmentation of the
      surface play a fundamental role. When the reaction is imaged in the 238-263 K
      temperature range (35 s/image acquisition time), a peculiar comblike propagation
      mechanism for the reaction front is found. Fast STM measurements (33 ms/image)
      prove that this mechanism holds also at room temperature, being therefore an
      intrinsic characteristic of the reaction on the 1D oxide. DFT calculations
      explain the observed behavior as due to the interplay between the lattice
      expansion in the initial surface and its relaxation during the reaction that
      leads to varying configurations for the reactants. At low temperatures, the
      reaction produces, in its final stages, a low-coverage, ordered patterning of the
      surface with residual oxygen. The pattern formation is related to the
      segmentation of the oxide phase.

PMID- 19173642
TI  - Ribosomal translocation: one step closer to the molecular mechanism.
AB  - Protein synthesis occurs in ribosomes, the targets of numerous antibiotics. How
      these large and complex machines read and move along mRNA have proven to be
      challenging questions. In this Review, we focus on translocation, the last step
      of the elongation cycle in which movement of tRNA and mRNA is catalyzed by
      elongation factor G. Translocation entails large-scale movements of the tRNAs and
      conformational changes in the ribosome that require numerous tertiary contacts to
      be disrupted and reformed. We highlight recent progress toward elucidating the
      molecular basis of translocation and how various antibiotics influence tRNA-mRNA
      movement.

PMID- 19173645
TI  - A fluorous-tagged "safety catch" linker for preparing heterocycles by ring
      closing metathesis.
AB  - A fluorous-tagged "safety catch" linker is described for the synthesis of
      heterocycles with use of ring-closing metathesis. The linker facilitates the
      purification of metathesis substrates, the removal of the catalyst, the
      functionalization of the products, and the release of only metathesis products.
      The synthesis of a range of heterocycles is described.

PMID- 19173646
TI  - PEG branched polymer for functionalization of nanomaterials with ultralong blood
      circulation.
AB  - Nanomaterials have been actively pursued for biological and medical applications
      in recent years. Here, we report the synthesis of several new poly(ethylene
      glycol) grafted branched polymers for functionalization of various nanomaterials
      including carbon nanotubes, gold nanoparticles (NPs), and gold nanorods (NRs),
      affording high aqueous solubility and stability for these materials. We
      synthesize different surfactant polymers based upon poly(gamma-glutamic acid)
      (gammaPGA) and poly(maleic anhydride-alt-1-octadecene) (PMHC18). We use the
      abundant free carboxylic acid groups of gammaPGA for attaching lipophilic species
      such as pyrene or phospholipid, which bind to nanomaterials via robust
      physisorption. Additionally, the remaining carboxylic acids on gammaPGA or the
      amine-reactive anhydrides of PMHC18 are then PEGylated, providing extended
      hydrophilic groups, affording polymeric amphiphiles. We show that single-walled
      carbon nanotubes (SWNTs), Au NPs, and NRs functionalized by the polymers exhibit
      high stability in aqueous solutions at different pH values, at elevated
      temperatures, and in serum. Moreover, the polymer-coated SWNTs exhibit remarkably
      long blood circulation (t(1/2) = 22.1 h) upon intravenous injection into mice,
      far exceeding the previous record of 5.4 h. The ultralong blood circulation time
      suggests greatly delayed clearance of nanomaterials by the reticuloendothelial
      system (RES) of mice, a highly desired property for in vivo applications of
      nanomaterials, including imaging and drug delivery.

PMID- 19173647
TI  - A mutagenesis-free approach to assignment of (19)F NMR resonances in
      biosynthetically labeled proteins.
AB  - Solution NMR studies of protein structure and dynamics using fluorinated amino
      acid probes are a valuable addition to the repertoire of existing (13)C, (15)N,
      and (1)H experiments. Despite the numerous advantages of the (19)F nucleus in
      NMR, protein studies are complicated by the dependence of resonance assignments
      on site-directed mutagenesis methods which are laborious and often problematic.
      Here we report an NMR-based route to the assignment of fluorine resonances in
      (13)C,(15)N-3-fluoro-l-tyrosine labeled calmodulin. The assignment begins with
      the correlation of the fluorine nucleus to the delta proton in the novel
      (13)C,(15)N-enriched probe which is achieved using a CT-HCCF-COSY experiment.
      Connection to the backbone is made through two additional solution NMR
      experiments, namely the (H(beta))C(beta)(C(gamma)C(delta))H(delta) and HNCACB.
      Assignments are completed using either previously published backbone chemical
      shift data or obtained experimentally provided uniform (13)C,(15)N labeling
      procedures are employed during protein expression. Additional benefits of the
      (13)C,(15)N-3-fluoro-l-tyrosine probe include the reduction of spectral overlap
      through ((13)C(19)F) CT-HSQCs, as well as the ability to monitor side chain
      dynamics using (19)F T(1), T(2), and the (13)C-(19)F NOE.

PMID- 19173648
TI  - A new synthesis of difluorodiazirine and the absolute reactivity of
      difluorocarbene.
AB  - Difluorodiazirine was generated by the reaction of 2,4
      dinitrophenoxyfluorodiazirine with lithium fluoride and 15-crown-5 in HMPA. Laser
      flash photolysis of difluorodiazirine afforded difluorocarbene (CF(2)). Absolute
      rate constants and activation parameters were determined for the additions of
      CF(2) to several alkenes.

PMID- 19173649
TI  - Enantioselective intramolecular Friedel-Crafts-type alpha-arylation of aldehydes.
AB  - Enantioselective organo-SOMO catalysis has, in the last two years, been the
      subject of considerable development and exploration. A number of new and unique
      transformations have been reported, such as alpha-allylation, alpha-oxyamination,
      alpha-enolation, and alpha-vinylation of aldehydes. Herein, we report a
      modification of this activation mode that involves the intramolecular Friedel
      Crafts-type alpha-arylation of aldehydes carrying electron-donating groups on
      their aromatic nucleus and its application to the total synthesis of demethyl
      calamenene, a potent cytotoxic agent against human adenocarcinoma A 549.

PMID- 19173650
TI  - Selective C-H activation alpha to primary amines. Bridging metallaaziridines for
      catalytic, intramolecular alpha-alkylation.
AB  - Selective alpha-C-H activation results in the synthesis of the first bridging
      metallaaziridine complex for the catalytic alpha-alkylation of primary amines.
      Reaction development led to the preparation of new Zr 2-pyridonate complexes for
      this useful transformation. No nitrogen protecting groups are required for this
      reaction, which is capable of assembling quaternary chiral centers alpha to
      nitrogen. Preliminary mechanistic investigations suggest bridging
      metallaaziridine species are the catalytically active intermediates for this
      alpha-functionalization reaction, while monomeric imido complexes furnish azepane
      hydroamination products.

PMID- 19173652
TI  - Optimizing a waveguide-based sandwich immunoassay for tumor biomarkers:
      evaluating fluorescent labels and functional surfaces.
AB  - The sensor team at the Los Alamos National Laboratory has developed a waveguide
      based optical biosensor for the detection of biomarkers associated with disease.
      We have previously demonstrated the application of this technology to the
      sensitive detection of carcinoembryonic antigen in serum and nipple aspirate
      fluid from breast cancer patients. In this publication, we report improvements to
      this technology that will facilitate transition to a point-of-care diagnostic
      system and/or robust research tool. The first improvement involved replacing
      phospholipid bilayers used for waveguide functionalization with self-assembled
      monolayers. These thin films are stable, specific, and robust silane-based
      surfaces that reduce nonspecific binding and enhance the signal to background
      ratio. Second, we have explored four different fluorescent labeling paradigms to
      determine the optimal procedure for use in the assay. Labeling the detector
      antibody with an organic dye (AlexaFluor 647) in the hinge region allows for
      unusual signal enhancement with repeat excitation (at 635 nm) in our assay
      format, thereby facilitating a better signal resolution at lower concentrations
      of the antigen. We have also labeled the detector antibody with photostable
      quantum dots through either the amine groups of lysine (Fc, NH) or using a
      histidine tag in the hinge region of the antibody (Hinge, H). Both labeling
      strategies allow for acceptable signal resolution, but quantum dots show much
      greater resistance to photobleaching than organic dyes.

PMID- 19173651
TI  - Direct vinylation of alcohols or aldehydes employing alkynes as vinyl donors: a
      ruthenium catalyzed C-C bond-forming transfer hydrogenation.
AB  - Under the conditions of ruthenium catalyzed transfer hydrogenation, 2-butyne
      couples to benzylic and aliphatic alcohols 1a-1l to furnish allylic alcohols 2a
      2l, constituting a direct C-H vinylation of alcohols employing alkynes as vinyl
      donors. Under related transfer hydrogenation conditions employing formic acid as
      terminal reductant, 2-butyne couples to aldehydes 4a, 4b, and 4e to furnish
      identical products of carbonyl vinylation 2a, 2b, and 2e. Thus, carbonyl
      vinylation is achieved from the alcohol or the aldehyde oxidation level in the
      absence of any stoichiometric metallic reagents. Nonsymmetric alkynes 6a-6c
      couple efficiently to aldehyde 4b to provide allylic alcohols 2m-2o as single
      regioisomers. Acetylenic aldehyde 7a engages in efficient intramolecular coupling
      to deliver cyclic allylic alcohol 8a.

PMID- 19173653
TI  - Influence of substitution pattern on solution behavior of hydroxypropyl
      methylcellulose.
AB  - Industrially produced hydroxypropyl methylcellulose (HPMC) is a chemically
      heterogeneous material, and it is thus difficult to predict parameters related to
      function on the basis of the polymer's average chemical values. In this study,
      the solution behavior of seven HPMC batches was correlated to the molecular
      weight, degree of substitution, and substituent pattern. The initial onset of
      phase separation, so-called clouding, generally followed an increased average
      molecular weight and degree of substitution. However, the slope of the clouding
      curve was affected by the substitution pattern, where the heterogeneously
      substituted batches had very shallow slopes. Further investigations showed that
      the appearance of a shallow slope of the clouding curve was a result of the
      formation of reversible polymer structures, formed as a result of the
      heterogeneous substituent pattern. These structures grew in size with temperature
      and concentration and resulted in an increase in the viscosity of the solutions
      at higher temperatures.

PMID- 19173654
TI  - Investigation of the interaction between Berberine and human serum albumin.
AB  - Berberine is an important traditional medicinal herb, which has been effectively
      used in the treatment of dysentery, diarrhea, stomatitis, throat infections, and
      hepatitis in folk medicine. In this study, the interaction between Berberine and
      human serum albumin (HSA) was investigated by fluorescence spectroscopy and UV
      vis absorbance spectroscopy. In the mechanism discussion, it was proved that the
      fluorescence quenching of HSA by berberine is a result of the formation of
      berberine-HSA complex. Fluorescence quenching constants were determined using the
      Stern-Volmer equation and Scatchard equation to provide a measure of the binding
      affinity between berberine and HSA. The results of thermodynamic parameters
      DeltaG, DeltaH, and DeltaS at different temperatures indicate that the
      electrostatic interactions play a major role for berberine-HSA association. Site
      marker competitive experiments indicated that the binding of berberine to HSA
      primarily took place in subdomain IIA. Furthermore, the distance r between donor
      (Trp-214) and acceptor (berberine) was obtained according to fluorescence
      resonance energy transfer (FRET).

PMID- 19173655
TI  - Thermodynamics of melittin binding to lipid bilayers. Aggregation and pore
      formation.
AB  - Lipid membranes act as catalysts for protein folding. Both alpha-helical and beta
      sheet structures can be induced by the interaction of peptides or proteins with
      lipid surfaces. Melittin, the main component of bee venom, is a particularly well
      studied example for the membrane-induced random coil-to-alpha-helix transition.
      Melittin in water adopts essentially a random coil conformation. The cationic
      amphipathic molecule has a high affinity for neutral and anionic lipid membranes
      and exhibits approximately 50-65% alpha-helix conformation in the membrane-bound
      state. At higher melittin concentrations, the peptide forms aggregates or pores
      in the membrane. In spite of the long-standing interest in melittin-lipid
      interactions, no systematic thermodynamic study is available. This is probably
      caused by the complexity of the binding process. Melittin binding to lipid
      vesicles is fast and occurs within milliseconds, but the binding process involves
      at least four steps, namely, (i) the electrostatic attraction of the cationic
      peptide to an anionic membrane surface, (ii) the hydrophobic insertion into the
      lipid membrane, (iii) the conformational change from random coil to alpha-helix,
      and (iv) peptide aggregation in the lipid phase. We have combined
      microelectrophoresis (measurement of the zeta potential), isothermal titration
      calorimetry, and circular dichroism spectroscopy to provide a thermodynamic
      analysis of the individual binding steps. We have compared melittin with a
      synthetic analogue, [D]-V(5,8),I(17),K(21)-melittin, for which alpha-helix
      formation is suppressed and replaced by beta-structure formation. The comparison
      reveals that the thermodynamic parameters for the membrane-induced alpha-helix
      formation of melittin are identical to those observed earlier for other peptides
      with an enthalpy h(helix) of -0.7 kcal/mol and a free energy g(helix) of -0.2
      kcal/mol per peptide residue. These thermodynamic parameters hence appear to be
      of general validity for lipid-induced membrane folding. As g(helix) is negative,
      it further follows that helix formation leads to an enhanced membrane binding for
      the peptides or proteins involved. In this study, melittin binds by approximately
      2 orders of magnitude better to the lipid membrane than [D]-V(5,8),I(17),K(21)
      melittin which cannot form an alpha-helix. We also found conditions under which
      the isothermal titration experiment reports only the aggregation process.
      Melittin aggregation is an entropy-driven process with an endothermic heat of
      reaction (DeltaH(agg)) of approximately 2 kcal/mol and an aggregation constant of
      20-40 M(-1).

PMID- 19173656
TI  - Chemical modification of epitaxial graphene: spontaneous grafting of aryl groups.
AB  - The addition of nitrophenyl groups to the surface of few-layer epitaxial graphene
      (EG) by the formation of covalent carbon-carbon bonds changed the electronic
      structure and transport properties of the EG from near-metallic to
      semiconducting.

PMID- 19173657
TI  - Competitive inhibition of uracil DNA glycosylase by a modified nucleotide whose
      triphosphate is a substrate for DNA polymerase.
AB  - Base excision repair (BER) enzymes are attractive targets for antiviral and
      anticancer agents. A number of nucleotides and nucleotide analogues are potent
      competitive inhibitors of BER glycosylases when they are incorporated into
      synthetic oligonucleotides. However, these molecules often are not substrates for
      DNA polymerases, which limits their utility in cells and as potential therapeutic
      agents. 1'-Cyano-2'-deoxyuridine (CNdU) is a nanomolar competitive inhibitor of
      uracil DNA glycosylase. In addition, the respective nucleotide triphosphate is
      accepted as a substrate by the Klenow fragment (exo(-)) of DNA polymerase I from
      E. coli. This is the first competitive inhibitor of UDG that is incorporated into
      DNA by Klenow exo(-), a model replicative polymerase. 1'-Cyano-2'-deoxyuridine
      (CNdU) and related molecules may prove useful as a new family of therapeutic or
      experimental agents that target DNA repair by using the cells' polymerase(s) to
      incorporate them into DNA. A potential benefit of such a mechanism is that
      multiple incorporations can occur for longer DNA molecules leading to
      amplification of the inhibitory effect beyond that seen here with short DNA
      duplexes.

PMID- 19173658
TI  - Hydrogenolysis of palladium(II) hydroxide and methoxide pincer complexes.
AB  - Hydrogenolysis reactions of palladium(II) hydroxide and methoxide complexes to
      form water and methanol, respectively, and the corresponding palladium(II)
      hydride are reported. In the presence of water, 1 was found to exist in solution
      as a water-bridged dimer; however, kinetic studies suggest the reaction of 1 and
      H(2) proceeds exclusively through the hydroxide monomer to form the palladium(II)
      hydride and water. Computational studies suggest a four-center intramolecular
      proton transfer as opposed to an oxidative addition/reductive elimination
      pathway.

PMID- 19173659
TI  - Nickel-catalyzed [4 + 2] cycloaddition of enones with alkynes.
AB  - A nickel-catalyzed [4 + 2] cycloaddition reaction has been developed where enones
      react with alkynes to afford polysubstituted pyrans. A mechanistic rationale is
      proposed, implying oxa-nickela cycle formation by oxidative cyclization of nickel
      to enone, followed by alkyne insertion.

PMID- 19173661
TI  - Identification of the water amidogen radical complex.
AB  - The water amidogen radical complex (H(2)O-NH(2)) is a reactive intermediate in
      the atmospheric oxidation of ammonia by a hydroxyl radical. In the present study,
      we identify for the first time the H(2)O-NH(2) complex using matrix isolation
      infrared spectroscopy. We corroborate our experimental findings with high level
      coupled cluster ab initio calculations.

PMID- 19173660
TI  - Porous nanoparticle supported lipid bilayers (protocells) as delivery vehicles.
AB  - Mixing liposomes with hydrophilic particles induces fusion of the liposome onto
      the particle surface. Such supported bilayers have been studied extensively as
      models of the cell membrane, while their applications in drug delivery have not
      been pursued. In this communication, we report liposome fusion on mesoporous
      particles as a synergistic means to simultaneously load and seal cargo within the
      porous core. We find fusion of a cationic lipid (DOTAP) on an anionic silica
      particle loads an anionic fluorescent dye (calcein) into the particle to a
      concentration exceeding 100x that in the surrounding medium. The loaded
      "protocell" particles are taken up efficiently by Chinese hamster ovary cells,
      where, due to a reduced pH within endosomal compartments, calcein is effectively
      released. Compared to some other nanoparticle systems, protocells provide a
      simple construct for cargo loading, sealing, delivery, and release. They promise
      to serve as useful vectors in nanomedicine.

PMID- 19173662
TI  - Growth of long, highly stable, and densely packed worm-like nanocolumns of hexa
      peri-hexabenzocoronenes via chemisorption on Au(111).
AB  - Long, highly stable, and densely packed edge-on nanocolumns of hexa-peri
      hexabenzocoronenes spontaneously grow from solution as self-assembled monolayers
      chemisorbed on gold.

PMID- 19173663
TI  - A temperature-sensitive liposomal 1H CEST and 19F contrast agent for MR image
      guided drug delivery.
AB  - A novel temperature-sensitive liposomal MRI contrast agent has been developed,
      which allows drug carrier localization using (1)H CEST with simultaneous
      quantification of the drug release using (19)F MR imaging in response to a local
      temperature increase.

PMID- 19173664
TI  - A hybrid electrochemical-colorimetric sensing platform for detection of
      explosives.
AB  - A highly selective, sensitive, and low-cost hybrid sensing platform is developed
      based on extraordinary properties of explosives in an ionic liquid and an
      integrated electrochemical and colorimetric approach.

PMID- 19173665
TI  - Total synthesis and structure elucidation of (+)-phorbasin C.
AB  - The first total synthesis and structure elucidation of a member of the phorbasin
      class of natural products is described.

PMID- 19173666
TI  - Symmetry controls the face geometry of DNA polyhedra.
AB  - Two complementary strategies have been developed to control the face geometry
      during the self-assembly of DNA polyhedra from branched DNA nanomotifs (tiles).
      In these approaches, any two interacting tiles are not equivalent in terms of
      either sequence or orientation; thus, each face must contain an even number of
      tiles. As a demonstration, DNA cubes, whose each face contains four tiles, have
      been assembled through these approaches.

PMID- 19173667
TI  - Impact of perfluorination on the charge-transport parameters of oligoacene
      crystals.
AB  - The charge-transport parameters of the perfluoropentacene and perfluorotetracene
      crystals are studied with a joint experimental and theoretical approach that
      combines gas-phase ultraviolet photoelectron spectroscopy and density functional
      theory. To gain a better understanding of the role of perfluorination, the
      results for perfluoropentacene and perfluorotetracene are compared to those for
      their parent oligoacenes, that is, pentacene and tetracene. Perfluorination is
      calculated to increase the ionization potentials and electron affinities by
      approximately 1 eV, which is expected to reduce significantly the injection
      barrier for electrons in organic electronics devices. Perfluorination also leads
      to significant changes in the crystalline packing, which greatly affects the
      electronic properties of the crystals and their charge-transport characteristics.
      The calculations predict large conduction and valence bandwidths and low hole and
      electron effective masses in the perfluoroacene crystals, with the largest
      mobilities expected along the pi-stacks. Perfluorination impacts as well both
      local and nonlocal vibrational couplings, whose strengths increase by a factor of
      about 2 with respect to the parent compounds.

PMID- 19173668
TI  - Micrometer- and nanometer-scale photopatterning using 2
      nitrophenylpropyloxycarbonyl-protected aminosiloxane monolayers.
AB  - An approach to nanopatterning is reported in which a scanning near-field optical
      microscope coupled to a near-UV laser is used to selectively deprotect 2
      nitrophenylpropyloxycarbonyl (NPPOC)-protected aminosiloxane monolayers on glass.
      UV deprotection was studied for unpatterned samples using X-ray photoelectron
      spectroscopy (XPS) and contact angle measurements. Highly efficient
      photodeprotection of the NPPOC moiety was observed upon irradiation at both 325
      and 364 nm, and complete deprotection was found to occur within minutes. The
      resulting amine-terminated surfaces were then derivatized using trifluoroacetic
      anhydride (TFAA) and aldehyde-functionalized polymer nanoparticles. Contact angle
      and XPS measurements postderivatization indicated that surface functionalization
      was extensive, with the NPPOC-deprotected surfaces and aminopropylsiloxane
      control materials exhibiting essentially identical characteristics. Micrometer
      scale patterns were fabricated using mask-based exposure, functionalized with
      polymer nanoparticles, and characterized by atomic force microscopy. Nanometer
      scale patterns were fabricated using near-field exposure and characterized by
      friction force microscopy. The nanopatterns were derivatized with TFAA. The
      resulting images exhibited a clear contrast inversion that was due to an
      inversion of surface polarity in the patterned areas and confirmed that high
      spatial resolution (ca. 100 nm) was readily achievable.

PMID- 19173675
TI  - Circulating CD34+/KDR+ endothelial progenitor cells are reduced in chronic heart
      failure patients as a function of Type D personality.
AB  - The aim of the present study was to assess whether EPC (endothelial progenitor
      cell) number/function might be an explanatory factor for the observed
      relationship between Type D personality (a joint tendency towards negative
      affectivity and social inhibition) and poor cardiovascular prognosis. We also
      assessed whether the effect of a single exercise bout on EPC number/function was
      affected by Type D personality. A total of 35 sedentary men with CHF (chronic
      heart failure; left ventricular ejection fraction <or=45%) underwent CPET
      (cardiopulmonary exercise testing) and personality assessment with the 14-item
      Type D scale. CD34+/KDR (kinase insert domain-containing receptor)+ cells were
      quantified by flow cytometry before and immediately after CPET. Migration of
      early EPC towards VEGF (vascular endothelial growth factor) and SDF-1alpha
      (stromal-cell-derived factor-1alpha) was investigated. Type D (n=10) and non-Type
      D (n=25) patients were comparable with regards to demographics, disease severity
      and Framingham risk factor score. Circulating EPC numbers were reduced by 54% in
      Type D compared with non-Type D patients (0.084+/-0.055 and 0.183+/-0.029% of
      lymphocytes respectively; P=0.006). Exercise led to a 60% increase in EPC in Type
      D patients, whereas the EPC number remained unchanged in the non-Type D group
      (P=0.049). Baseline migratory capacity was related to disease severity, but was
      not different between Type D and non-Type D patients. Exercise induced a highly
      significant enhancement of migratory capacity in both groups. In conclusion,
      reduced EPC numbers might explain the impaired cardiovascular outcome in Type D
      patients. The larger increase in circulating EPCs observed in these patients
      suggests that acute exercise elicits a more pronounced stimulus for endothelial
      repair.

PMID- 19173676
TI  - Comparison of the retinal microvasculature in European and African-Caribbean
      people with diabetes.
AB  - Diabetes aggravates the impact of elevated BP (blood pressure) on the
      microcirculation, and people of African ancestry with diabetes are more
      susceptible to microvascular damage than Europeans. In the present study, we
      investigated possible differences in the retinal microcirculation in people of
      European and African-Caribbean ethnicity with diabetes that might account for
      this. A total of 51 subjects with Type 2 diabetes (age 40-65 years; 25 male; 29
      African-Caribbean) were studied. Clinic and 24 h ambulatory BP, and fasting
      glucose, insulin and lipids were measured. Digital retinal images were analysed
      using custom-written semi-automatic software to determine: LDR (length/diameter
      ratio) and AVR (arteriolar/venular diameter ratio), branching angles, vessel
      tortuosity and NT (number of terminal vessel branches). Arterioles were narrower
      in European people with diabetes than in African-Caribbean people with diabetes
      [mean (S.D.) arteriolar diameter, 76 (7) compared with 82 (11) microm
      respectively (P=0.03); arteriolar LDR, 28.1 (8.5) compared with 23.7 (7.0)
      respectively (P=0.046); and AVR, 0.66 (0.21) compared with 0.90 (0.36)
      respectively (P=0.028)]. Ethnic differences in arteriolar LDR, arteriolar
      diameter and AVR were not explained by differences in BP, but were attenuated by
      adjustment for the duration of diabetes. There was no significant relationship
      between BP and arteriolar narrowing in the group as a whole, although the
      relationship between arteriolar LDR and systolic BP was stronger in Europeans
      than African-Caribbeans [beta=0.08 (0.07) compared with beta=0.03 (0.06);
      P=0.03]. In conclusion, in the presence of diabetes, a relationship between BP
      and retinal arteriolar diameter was not evident and implies impaired small artery
      remodelling in the presence of diabetes. African-Caribbean people with diabetes
      have wider retinal arterioles and this could contribute to enhanced microvascular
      damage in this ethnic group.

PMID- 19173677
TI  - The soluble metal-binding domain of the copper transporter ATP7B binds and
      detoxifies cisplatin.
AB  - Wilson disease ATPase (ATP7B) has been implicated in the resistance of cancer
      cells to cisplatin. Using a simple in vivo assay in bacterial culture, in the
      present study we demonstrate that ATP7B can confer resistance to cisplatin by
      sequestering the drug in its N-terminal metal-binding domain without active drug
      extrusion from the cell. Expression of a protein fragment containing four N
      terminal MBRs (metal-binding repeats) of ATP7B (MBR1-4) protects cells from the
      toxic effects of cisplatin. One MBR1-4 molecule binds up to three cisplatin
      molecules at the copper-binding sites in the MBRs. The findings of the present
      study suggest that suppressing enzymatic activity of ATP7B may not be an
      effective way of combating cisplatin resistance. Rather, the efforts should be
      directed at preventing cisplatin binding to the protein.

PMID- 19173678
TI  - Retinoids synergize with insulin to induce hepatic Gck expression.
AB  - Hepatic GK (glucokinase) plays a key role in maintaining glucose homoeostasis.
      Many stimuli regulate GK activity by controlling its gene transcription. We
      hypothesized that endogenous lipophilic molecules modulate hepatic Gck
      expression. Lipophilic molecules were extracted from rat livers, saponified and
      re-constituted as an LE (lipophilic extract). LE synergized with insulin to
      induce primary hepatocyte, but not beta-cell, Gck expression in an SREBP-1c
      (sterol-regulatory-element-binding protein-1c)-independent manner. The dramatic
      induction of Gck mRNA resulted in a significant increase in GK activity.
      Subsequently, the active molecules were identified as retinol and retinal by MS
      after the purification of the active LE fractions. Retinoids synergized with
      insulin to induce Gck expression by the activation of both RAR [RA (retinoic
      acid) receptor] and RXR (retinoid X receptor). Inhibition of RAR activation
      completely abolished the effect of retinal. The hepatic GK specific activity and
      Gck mRNA levels of Zucker lean rats fed with a VAD [VA (vitamin A)-deficient]
      diet were significantly lower than those of rats fed with VAS (VA-sufficient)
      diet. Additionally, the hepatic Gck mRNA expression of Sprague-Dawley rats fed
      with a VAD diet was lower than that of rats fed with VA-marginal, -adequate or 
      supplemented diets. The reduced expression of Gck mRNA was increased after an
      intraperitoneal dose of RA in VAD rats. Furthermore, an intravenous injection of
      RA rapidly raised hepatic Gck expression in rats fed with a VAS control diet.
      Understanding the underlying mechanism that mediates the synergy may be helpful
      for developing a treatment strategy for patients with diabetes.

PMID- 19173679
TI  - Branched-chain 2-oxoacid transamination increases GABA-shunt metabolism and
      insulin secretion in isolated islets.
AB  - We have previously shown that oxo-4-methylpentanoate promotes islet GABA (gamma
      aminobutyric acid) metabolism and stimulates insulin secretion. The main aim of
      this work was to explore the participation of the transamination of branched
      chain 2-oxoacids in these processes with the aid of several inhibitors of this
      enzyme activity. No correlation was found between the transamination of branched
      chain 2-oxoacids in islet homogenates and insulin secretion. However, in vivo
      transamination rates correlated better with the secretion capacity of the
      different branched-chain 2-oxoacids. Gabapentin, a specific inhibitor of the
      cytosolic isoenzyme, showed greater potential to decrease the in vitro
      transamination rates of oxo-3-methylbutyrate and oxo-3-methylpentanoate than
      those of oxo-4-methylpentanoate and oxohexanoate; this correlated with its
      capacity to decrease insulin secretion. 4-Methylvaleric acid very strongly
      inhibited the transamination of all the branched-chain 2-oxoacids and blocked
      their capacity to decrease islet GABA and to stimulate insulin secretion. KCl at
      70 mM at stimulated islet GABA release, subsequently decreasing its tissue
      concentration. This 'non-metabolic' decrease of GABA suppressed the second phase
      of insulin secretion triggered by oxo-4-methylpentanoate and oxohexanoate. Oxo-4
      methylpentanoate and oxo-3-methylpentanoate suppressed dose-dependent 2
      oxoglutarate dehydrogenase activity in islet homogenates. In conclusion, the
      transamination of branchedchain 2-oxoacids is more important to the stimulation
      of insulin secretion than their catabolism, and transamination decreases islet
      GABA concentrations by promoting GABA metabolism. Also, inhibition of 2
      oxoglutarate dehydrogenase by branched-chain 2-oxoacids may increase metabolic
      flux in the 'GABA-shunt' at the expense of reduced tricarboxylic acid cycle flux.

PMID- 19173680
TI  - Impact of the haplotypes of the human pregnane X receptor gene on the basal and
      St John's wort-induced activity of cytochrome P450 3A4 enzyme.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Human pregnane X receptor (PXR/NR1I2)
      is a key regulator of cytochrome P450 3A4. To date, there are 198 reported SNPs
      for the human PXR/NR1I2 gene. Some of these SNPs are found to affect the inducing
      ability of PXR to CYP3A4. WHAT THIS STUDY ADDS: This study, for the first time,
      has investigated the effect of PXR haplotype on basal and St John's wort-induced
      CYP3A4 activity in humans. H1/H1 of the PXR gene had weaker basal transcriptional
      activity but greater inducible transcriptional activity to CYP3A4 than H1/H2 and
      H2/H2. AIMS: Human pregnane X receptor (PXR/NR1I2) is the master regulator of
      CYP3A4, which metabolizes >50% of drugs on the market. This study investigated
      the relationship between the two most frequent haplotypes [H1 (TCAGGGGCCACC) and
      H2 (CCGAAAACTAAT)] of PXR and basal and St John's wort (SJW)-induced CYP3A4
      activity. METHODS: Ten healthy subjects carrying H1 and H2 haplotypes (three
      subjects with H1/H1, four with H1/H2 and three with H2/H2) entered this study.
      The 10 subjects did not carry CYP3A4*4, *5 and *6. All subjects were
      administrated a 300-mg SJW tablet three times daily for 14 days, and CYP3A4
      activity was measured using nifedipine (NIF) as a probe. The plasma
      concentrations of NIF and dehydronifedipine (DNIF) were determined by a validated
      liquid chromatography/mass spectrometry/mass spectrometry method. RESULTS: After
      administration of SJW, the AUC(0-infinity) of NIF decreased significantly, and
      the AUC(0-infinity) of DNIF increased significantly (P < 0.05). For H1/H2, the
      AUC(0-infinity) of NIF decreased by 42.4%, and the AUC(0-infinity) of DNIF
      increased by 20.2%; for H2/H2, the AUC(0-infinity) of NIF decreased by 47.9%, and
      the AUC(0-infinity) of DNIF increased by 33.0%; for H1/H1, the AUC(0-infinity) of
      NIF decreased by 29.0%, yet the AUC(0-infinity) of DNIF increased by 106.7%. The
      increase of the AUC(0-infinity) of DNIF in H1/H1 was significantly different from
      the other two haplotype pairs (P < 0.05). Meanwhile, before administration of
      SJW, the ratio of AUC(0-infinity(DNIF))/AUC(0-infinity(NIF)) was the lowest for
      H1/H1 (22.1%), compared with H1/H2 (58.7%) and H2/H2 (30.0%). CONCLUSIONS: H1/H1
      of the human PXR gene had weaker basal transcriptional activity but greater
      inducible transcriptional activity to CYP3A4 than H1/H2 and H2/H2.

PMID- 19173681
TI  - Population pharmacokinetics of intravenous pantoprazole in paediatric intensive
      care patients.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The use of intravenous pantoprazole, a
      proton pump inhibitor, has been increasing in the paediatric intensive care unit.
      Despite this increased use, data on the disposition of intravenous pantoprazole
      in paediatric intensive care patients are very scarce. WHAT THIS STUDY ADDS: Our
      population approach has determined the pharmacokinetic parameters of intravenous
      pantoprazole in paediatric intensive care patients and the relative importance of
      factors influencing its disposition. Pantoprazole clearance was significantly
      influenced by developmental changes and by the presence of systemic inflammatory
      syndrome, hepatic dysfunction and CYP2C19 inhibitors. AIMS: To characterize the
      pharmacokinetics of intravenous pantoprazole in a paediatric intensive care
      population and to determine the influence of demographic factors, systemic
      inflammatory response syndrome (SIRS), hepatic dysfunction and concomitantly used
      CYP2C19 inducers and inhibitors on the drug's pharmacokinetics. METHODS: A total
      of 156 pantoprazole concentration measurements from 20 patients (10 days to 16.4
      years of age) at risk for or with upper gastrointestinal bleeding, who received
      pantoprazole doses ranging from 19.9 to 140.6 mg/1.73 m(2)/day, were analysed
      using a population pharmacokinetic approach (nonmem program). RESULTS: The best
      structural model for pantoprazole was a two-compartment model with zero order
      infusion and first-order elimination. Body weight, SIRS, age, hepatic dysfunction
      and presence of CYP2C19 inhibitors were significant covariates affecting
      clearance (CL), accounting for 75% of interindividual variability. Only body
      weight significantly influenced central volume of distribution (V(c)). In the
      final population model, the estimated CL and V(c) were 5.28 l h(-1) and 2.22 l,
      respectively, for a typical 5-year-old child weighing 20 kg. Pantoprazole CL
      increased with weight and age, whereas the presence of SIRS, CYP2C19 inhibitors
      and hepatic dysfunction, when present separately, significantly decreased
      pantoprazole CL by 62.3, 65.8 and 50.5%, respectively. For patients aged between
      6 months and 5 years without SIRS, CYP2C19 inhibitor or hepatic dysfunction, the
      predicted pantoprazole CL is faster than that reported in adults. CONCLUSION:
      These results provide important information for physicians regarding selection of
      a starting dose and dosing regimens of pantoprazole for paediatric intensive care
      patients based on factors frequently encountered in this population.

PMID- 19173682
TI  - Faecal short chain fatty acid pattern and allergy in early childhood.
AB  - AIM: To investigate whether functional changes of the gut flora over time were
      related to sensitization and allergic symptoms at four years of age. METHODS: The
      levels of short chain fatty acids (SCFAs) in faecal samples at one (n = 139) and
      four (n = 53) years of age were related to the development of positive skin prick
      tests (SPT) and allergic symptoms during the first four years of life. RESULTS:
      Faecal acetic (p < 0.01) and propionic (p < 0.01) acids decreased from one to
      four years of age, while valeric acid (p < 0.001) increased. Low levels of i
      butyric (p = 0.01), i-valeric (p = 0.03) and valeric acids (p = 0.02) at one year
      were associated with questionnaire-reported symptoms of food allergy at four
      years. Positive SPTs and allergic symptoms at four years were associated with low
      faecal levels of i-butyric, i-valeric and valeric acids. At one year of age,
      infants with, as compared to without older siblings had higher median levels of
      valeric acid. CONCLUSION: A slow functional maturation of the gut microflora, as
      measured by faecal levels of SCFAs is associated with allergy both at one and
      four years. The findings lend further support to an association between allergy
      and the development of microbial diversity.

PMID- 19173683
TI  - Autism spectrum disorder in children with and without epilepsy: impact on social
      functioning and communication.
AB  - AIM: To compare developmental and psychological functioning in two groups of
      children with autism spectrum disorder (asd), one with epilepsy and one without.
      METHODS: Sixty 7-17-year-old children in each group were recruited through a
      range of services in order to screen as representative a sample as possible.
      Parents were interviewed using the diagnostic interview for social and
      communication disorders (DISCO-11), and children were clinically examined and
      their medical histories assessed. RESULTS: The asd and epilepsy (asd+e) group
      demonstrated a substantially more even gender ratio, with a greater proportion of
      girls. They were more likely to have received later asd diagnoses and additional
      medical diagnoses. They also showed more motor difficulties, developmental delays
      and challenging behaviours, but were no more likely to be aloof and passive. The
      asd-only group experienced more abnormal fascinations with objects and used brief
      glances as a means of eye contact more than the asd+e group. CONCLUSION: Results
      support important between-group differences with diagnostic and therapeutic
      implications. asds often present atypically in children with seizures. However,
      both groups showed widely varying social and linguistic presentations.

PMID- 19173684
TI  - Intraocular lens as a drug delivery system for dexamethasone.
AB  - PURPOSE: To evaluate the effect of an intraocular lens (IOL) coated with
      dexamethasone on postoperative inflammation after cataract surgery. METHODS:
      Clear lens extraction was performed bilaterally in eight 8-week-old rabbits. An
      uncoated silicone IOL (CeeOn; AMO, Santa Ana, CA, USA) was implanted in one
      randomly selected eye. In the other eye, the same silicone IOL model was
      implanted but was coated with dexamethasone. Aqueous humour was obtained
      preoperatively and on days 1, 3, 7, 14 and 28 postoperatively. Three inflammatory
      parameters were measured and compared between the eyes: prostaglandin E2 (PGE2),
      white blood cell (WBC) count and protein content. The animals were killed on day
      28 postoperatively. RESULTS: PGE2 levels measured on days 1, 3 and 7 were
      significantly lower in eyes with a coated IOL compared to eyes with an uncoated
      IOL (p < 0.01). The WBC count was significantly lower in eyes with a coated IOL
      on days 1 (p < 0.01) and 3 (p < 0.05). There was significantly less protein in
      eyes with a coated IOL on days 1 and 3 (p < 0.01). CONCLUSION: Coating a silicone
      IOL with dexamethasone significantly reduced postoperative inflammation after
      clear lens extraction in rabbits.

PMID- 19173685
TI  - Successful treatment of longstanding vasospastic central retinal artery
      occlusion.

PMID- 19173686
TI  - Living without aprotinin: the results of a 5-year blood saving program in cardiac
      surgery.
AB  - BACKGROUND: After 20 years of regular use in cardiac surgery patients, aprotinin
      has recently been withdrawn from the market due to many concerns about its
      safety. For a number of reasons aprotinin has not been available in Italy since
      1998. The present study presents an aprotinin-free treatment protocol applied at
      our institution during the last 5 years, and aims to verify the results of this
      protocol in terms of allogeneic blood product transfusions, postoperative blood
      loss and surgical re-exploration rate. METHODS: Retrospective study on 7988
      consecutive patients who underwent cardiac surgery during the years 2003-2007.
      All the patients received specific hemostasis/coagulation management based on (a)
      routine use of tranexamic acid, (b) heparin dose-response monitoring,
      thromboelastography, platelet (PLT) function analysis in a select population of
      patients, and (c) use of fresh frozen plasma (FFP), PLTs, and desmopressin
      according to the hemostasis/coagulation profile. Data retrieved from the
      institutional database were quantity of packed red cells (PRCs), FFP, PLT
      transfusion rate, blood loss in the first 12 postoperative hours, and surgical re
      exploration rate. RESULTS: PRCs were transfused in 40.4% of patients (with higher
      rates for selected high-risk subpopulations), FFP in 12.9% and PLTs in 2.6%.
      Surgical re-exploration rate was 3.7%. With respect to historical controls, a
      significant reduction of PRCs and FFP transfusions was obtained using closed
      circuits, point of care coagulation tests, and combination of the two.
      CONCLUSION: This aprotinin-free blood saving program is an effective strategy for
      allogeneic blood products transfusion containment.

PMID- 19173687
TI  - We should work less at night.
AB  - There is growing amount of evidence that doctors' performance is poorer if they
      work for over-prolonged duties or at night. These working patterns decrease the
      standard of care and increase the health care expenses. Furthermore, night
      workers have serious health risks due to their non-physiological work shifts.
      Effective ways to reduce the overall consequences of fatigue and night work
      include minimising the amount of work carried out at nighttime and setting up
      rules for maximal hours for each work shift.

PMID- 19173688
TI  - Depth of anaesthesia monitoring in obese patients: a randomized study of propofol
      remifentanil.
AB  - BACKGROUND: In obese patients, depth of anaesthesia monitoring could be useful in
      titrating intravenous anaesthetics. We hypothesized that depth of anaesthesia
      monitoring would reduce recovery time and use of anaesthetics in obese patients
      receiving propofol and remifentanil. METHODS: We investigated 38 patients with a
      body mass index >or=30 kg/m(2) scheduled for an abdominal hysterectomy. Patients
      were randomized to either titration of propofol and remifentanil according to a
      cerebral state monitor (CSM group) or according to usual clinical criteria
      (control group). The primary end point was time to eye opening and this was
      assessed by a blinded observer. RESULTS: Time to eye opening was 11.8 min in the
      CSM group vs. 13.4 min in the control group (P=0.58). The average infusion rate
      for propofol was a median of 516 vs. 617 mg/h (P=0.24) and for remifentanil 2393
      vs. 2708 microg/h (P=0.04). During surgery, when the cerebral state index was
      continuously between 40 and 60, the corresponding optimal propofol infusion rate
      was 10 mg/kg/h based on ideal body weight. CONCLUSION: No significant reduction
      in time to eye opening could be demonstrated when a CSM was used to titrate
      propofol and remifentanil in obese patients undergoing a hysterectomy. A
      significant reduction in remifentanil consumption was found.

PMID- 19173689
TI  - Comparison of intrathecal magnesium, fentanyl, or placebo combined with
      bupivacaine 0.5% for parturients undergoing elective cesarean delivery.
AB  - BACKGROUND: Intrathecal (i.t.) administration of magnesium has been reported to
      potentiate opioid antinociception in rats and humans. In this prospective,
      randomized, double-blind, study, we investigated the sensory, motor, and
      analgesic block characteristics of i.t. magnesium 50 mg compared with fentanyl 25
      microg and saline when added to 0.5% bupivacaine (10 mg). METHODS: Ninety ASA I
      or II adult patients undergoing cesarean section were randomly allocated to
      receive 1.0 ml of 0.9% sodium chloride in group S, 50 mg of magnesium sulfate
      (1.0 ml) 5% in group M, or 25 microg of fentanyl (1.0 ml) in group F following 10
      mg of bupivacaine 0.5% i.t. We recorded the following: onset and duration of
      sensory and motor block, maximal sensory block height, the time to reach the
      maximal dermatomal level of sensory block, and the duration of spinal anesthesia.
      RESULTS: Magnesium did not shorten the onset time of sensory and motor blockade
      or prolong the duration of spinal anesthesia. The duration of sensory (P<0.032)
      and motor (P<0.002) blockade was significantly shorter in M and S groups than in
      the F group. The time to reach the maximal dermatomal level of sensory block was
      significantly shorter in the F group than in the S and M groups (P<0.002).
      CONCLUSION: In patients undergoing cesarean section with spinal anesthesia, the
      addition of magnesium sulfate (50 mg) i.t. to 10 mg of spinal bupivacaine (0.5%)
      did not shorten the onset time of sensory and motor blockade or prolong the
      duration of spinal anesthesia, as seen with fentanyl.

PMID- 19173690
TI  - Equal effects of gelatin and hydroxyethyl starch (6% HES 130/0.42) on modified
      thrombelastography in children.
AB  - BACKGROUND: Artificial colloids are frequently used to prevent or treat
      circulatory failure due to hypovolaemia. Whereas gelatin has been shown not to
      affect coagulation besides its haemodilutional effect, hydroxyethyl starches
      (HES) have additional negative effects on haemostasis. The third-generation HES
      solutions have been developed to minimise these effects. We therefore conducted a
      prospective, randomised study, to verify the hypothesis that a 6% HES 130/0.42/6
      : 1 and a 4% gelatin infusion influences modified thrombelastography (TEM)
      parameters in children in the same manner and to the same extent. METHODS: A
      total of 50 paediatric patients aged 0-12 years scheduled for surgery were
      assigned to receive either 10 ml/kg HES 130/0.42 or gelatin. Blood gas analysis,
      haemodynamic parameters and TEM measurements were performed before and after
      colloid administration. RESULTS: Patient characteristics, indications/surgical
      procedures and the main results obtained from blood gas analysis were comparable
      between the two groups. After administration of either gelatin or HES, all TEM
      parameters, except for clotting time, indicated impaired coagulation whereas the
      mean values of all TEM parameters remained within the normal ranges. Comparing
      the gelatin and HES 130/0.42/6 : 1 groups, none of the measured TEM parameters
      was found to show between-group differences at baseline or after colloid
      infusion. CONCLUSION: In conclusion, we could demonstrate that the
      investigational product, HES 130/0.42/6 : 1 solution, administered at a dosage of
      10 ml/kg to children, had comparable effects on coagulation monitored with TEM as
      a gelatin solution. Perioperative administration of HES 130/0.42/6 : 1 does not
      alter coagulation to an extent above and beyond the effect of haemodilution.

PMID- 19173691
TI  - Impact of a regional anesthesia rotation on ultrasonographic identification of
      anatomic structures by anesthesiology residents.
AB  - OBJECTIVE: The specific aim of this study was to determine the ability of
      anesthesiology residents to independently identify a series of anatomic
      structures in a live model using ultrasound, both before and after a 4-week
      regional anesthesia rotation that incorporates a standardized ultrasound training
      curriculum for peripheral nerve blockade. METHODS: Ten CA2 and CA3 anesthesiology
      residents volunteered to participate in this study. Each resident was subjected
      to a pre-rotation practical exam, in which he attempted to identify 15 structures
      at four sites of peripheral nerve blockade, in a test subject. Each resident then
      received specific training for ultrasound-guided nerve blocks during a 4-week
      regional anesthesia rotation, and then completed a post-rotation exam. The mean
      number of structures correctly identified on the exams was compared for
      significant differences utilizing a paired t-test. RESULTS: Residents were able
      to identify significantly more anatomic structures on the post-rotation exam as
      compared with the pre-rotation exam (mean 14.1 vs. 9.9, P<.001), as well as more
      peripheral nerve targets. The most frequently misidentified structures on the pre
      rotation exam were the subclavian vein, the sciatic nerve in the popliteal fossa,
      and the femur. CONCLUSIONS: Ultrasound-naive anesthesiology residents, who
      received instruction and experience with ultrasound-guided peripheral nerve
      blocks on a 4-week regional anesthesia rotation, significantly improved their
      ability to independently identify relevant anatomic structures with
      ultrasonography.

PMID- 19173692
TI  - A multilevel model for continuous time population estimation.
AB  - Statistical methods have been developed and applied to estimating populations
      that are difficult or too costly to enumerate. Known as multilist methods in
      epidemiological settings, individuals are matched across lists and estimation of
      population size proceeds by modeling counts in incomplete multidimensional
      contingency tables (based on patterns of presence/absence on lists). As multilist
      methods typically assume that lists are compiled instantaneously, there are few
      options available for estimating the unknown size of a closed population based on
      continuously (longitudinally) compiled lists. However, in epidemiological
      settings, continuous time lists are a routine byproduct of administrative
      functions. Existing methods are based on time-to-event analyses with a second
      step of estimating population size. We propose an alternative approach to address
      the twofold epidemiological problem of estimating population size and of
      identifying patient factors related to duration (in days) between visits to a
      health care facility. A Bayesian framework is proposed to model interval lengths
      because, for many patients, the data are sparse; many patients were observed only
      once or twice. The proposed method is applied to the motivating data to
      illustrate the methods' applicability. Then, a small simulation study explores
      the performance of the estimator under a variety of conditions. Finally, a small
      discussion section suggests opportunities for continued methodological
      development for continuous time population estimation.

PMID- 19173693
TI  - Flexible regression model selection for survival probabilities: with application
      to AIDS.
AB  - Clinicians are often interested in the effect of covariates on survival
      probabilities at prespecified study times. Because different factors can be
      associated with the risk of short- and long-term failure, a flexible modeling
      strategy is pursued. Given a set of multiple candidate working models, an
      objective methodology is proposed that aims to construct consistent and
      asymptotically normal estimators of regression coefficients and average
      prediction error for each working model, that are free from the nuisance
      censoring variable. It requires the conditional distribution of censoring given
      covariates to be modeled. The model selection strategy uses stepup or stepdown
      multiple hypothesis testing procedures that control either the proportion of
      false positives or generalized familywise error rate when comparing models based
      on estimates of average prediction error. The context can actually be cast as a
      missing data problem, where augmented inverse probability weighted complete case
      estimators of regression coefficients and prediction error can be used (Tsiatis,
      2006, Semiparametric Theory and Missing Data). A simulation study and an
      interesting analysis of a recent AIDS trial are provided.

PMID- 19173694
TI  - Adaptive randomization for multiarm comparative clinical trials based on joint
      efficacy/toxicity outcomes.
AB  - We present an outcome-adaptive randomization (AR) scheme for comparative clinical
      trials in which the primary endpoint is a joint efficacy/toxicity outcome. Under
      the proposed scheme, the randomization probabilities are unbalanced adaptively in
      favor of treatments with superior joint outcomes characterized by higher efficacy
      and lower toxicity. This type of scheme is advantageous from the patients'
      perspective because on average, more patients are randomized to superior
      treatments. We extend the approximate Bayesian time-to-event model in Cheung and
      Thall (2002, Biometrics 58, 89-97) to model the joint efficacy/toxicity outcomes
      and perform posterior computation based on a latent variable approach.
      Consequently, this allows us to incorporate essential information about patients
      with incomplete follow-up. Based on the computed posterior probabilities, we
      propose an AR scheme that favors the treatments with larger joint probabilities
      of efficacy and no toxicity. We illustrate our methodology with a leukemia trial
      that compares three treatments in terms of their 52-week molecular remission
      rates and 52-week toxicity rates.

PMID- 19173695
TI  - Flexible designs for genomewide association studies.
AB  - Genomewide association studies attempting to unravel the genetic etiology of
      complex traits have recently gained attention. Frequently, these studies employ a
      sequential genotyping strategy: A large panel of markers is examined in a
      subsample of subjects, and the most promising markers are genotyped in the
      remaining subjects. In this article, we introduce a novel method for such designs
      enabling investigators to, for example, modify marker densities and sample
      proportions while strongly controlling the family-wise type I error rate. Loss of
      efficiency is avoided by redistributing conditional type I error rates of
      discarded markers. Our approach can be combined with cost optimal designs and
      entails a greater flexibility than all previously suggested designs. Among other
      features, it allows for marker selections based upon biological criteria instead
      of statistical criteria alone, or the option to modify the sample size at any
      time during the course of the project. For practical applicability, we develop a
      new algorithm, subsequently evaluate it by simulations, and illustrate it using a
      real data set.

PMID- 19173696
TI  - Estimation in semiparametric transition measurement error models for longitudinal
      data.
AB  - We consider semiparametric transition measurement error models for longitudinal
      data, where one of the covariates is measured with error in transition models,
      and no distributional assumption is made for the underlying unobserved covariate.
      An estimating equation approach based on the pseudo conditional score method is
      proposed. We show the resulting estimators of the regression coefficients are
      consistent and asymptotically normal. We also discuss the issue of efficiency
      loss. Simulation studies are conducted to examine the finite-sample performance
      of our estimators. The longitudinal AIDS Costs and Services Utilization Survey
      data are analyzed for illustration.

PMID- 19173697
TI  - Latent-model robustness in joint models for a primary endpoint and a longitudinal
      process.
AB  - Joint modeling of a primary response and a longitudinal process via shared random
      effects is widely used in many areas of application. Likelihood-based inference
      on joint models requires model specification of the random effects. Inappropriate
      model specification of random effects can compromise inference. We present
      methods to diagnose random effect model misspecification of the type that leads
      to biased inference on joint models. The methods are illustrated via application
      to simulated data, and by application to data from a study of bone mineral
      density in perimenopausal women and data from an HIV clinical trial.

PMID- 19173698
TI  - Applications of extensions of bivariate rank sum statistics to the crossover
      design to compare two treatments through four sequence groups.
AB  - This article describes applications of extensions of bivariate rank sum
      statistics to the crossover design with four sequence groups for two treatments.
      A randomized clinical trial in ophthalmology provides motivating background for
      the discussion. The bilateral design for this study has four sequence groups T:T,
      T:P, P:T, and P:P, respectively, for T as test treatment or P as placebo in the
      corresponding order for the left and right eyes. This article describes how to
      use the average of the separate Wilcoxon rank sum statistics for the left and
      right eyes for the overall comparison between T and P with the correlation
      between the two eyes taken into account. An extension of this criterion with
      better sensitivity to potential differences between T and P through reduction of
      the applicable variance has discussion in terms of a conceptual model with
      constraints for within-side homogeneity of groups with the same treatment and
      between-side homogeneity of the differences between T and P. Goodness of fit for
      this model can have assessment with test statistics for its corresponding
      constraints. Simulation studies for the conceptual model confirm better power for
      the extended test statistic with its full invocation than other criteria without
      this property. The methods summarized here are illustrated for the motivating
      clinical trial in ophthalmology, but they are applicable to other situations with
      the crossover design with four sequence groups for either two locations for two
      treatments at the same time for a patient or two successive periods for the
      assigned treatments for a recurrent disorder. This article also notes that the
      methods based on its conceptual model can have unsatisfactory power for
      departures from that model where the difference between T and P via the T:T and
      P:P groups is not similar to that via the T:P and P:T groups, as might occur when
      T has a systemic effect in a bilateral trial. For this situation, more robust
      test statistics have identification, but there is recognition that the parallel
      groups design with only the T:T and P:P groups may be more useful than the
      bilateral design with four sequence groups.

PMID- 19173699
TI  - Covariate adjusted correlation analysis with application to FMR1 premutation
      female carrier data.
AB  - Motivated by molecular data on female premutation carriers of the fragile X
      mental retardation 1 (FMR1) gene, we present a new method of covariate adjusted
      correlation analysis to examine the association of messenger RNA (mRNA) and
      number of CGG repeat expansion in the FMR1 gene. The association between the
      molecular variables in female carriers needs to adjust for activation ratio
      (ActRatio), a measure which accounts for the protective effects of one normal X
      chromosome in females carriers. However, there are inherent uncertainties in the
      exact effects of ActRatio on the molecular measures of interest. To account for
      these uncertainties, we develop a flexible adjustment that accommodates both
      additive and multiplicative effects of ActRatio nonparametrically. The proposed
      adjusted correlation uses local conditional correlations, which are local method
      of moments estimators, to estimate the Pearson correlation between two variables
      adjusted for a third observable covariate. The local method of moments estimators
      are averaged to arrive at the final covariate adjusted correlation estimator,
      which is shown to be consistent. We also develop a test to check the
      nonparametric joint additive and multiplicative adjustment form. Simulation
      studies illustrate the efficacy of the proposed method. (Application to FMR1
      premutation data on 165 female carriers indicates that the association between
      mRNA and CGG repeat after adjusting for ActRatio is stronger.) Finally, the
      results provide independent support for a specific jointly additive and
      multiplicative adjustment form for ActRatio previously proposed in the
      literature.

PMID- 19173700
TI  - A semiparametric joint model for longitudinal and survival data with application
      to hemodialysis study.
AB  - In many longitudinal clinical studies, the level and progression rate of
      repeatedly measured biomarkers on each subject quantify the severity of the
      disease and that subject's susceptibility to progression of the disease. It is of
      scientific and clinical interest to relate such quantities to a later time-to
      event clinical endpoint such as patient survival. This is usually done with a
      shared parameter model. In such models, the longitudinal biomarker data and the
      survival outcome of each subject are assumed to be conditionally independent
      given subject-level severity or susceptibility (also called frailty in
      statistical terms). In this article, we study the case where the conditional
      distribution of longitudinal data is modeled by a linear mixed-effect model, and
      the conditional distribution of the survival data is given by a Cox proportional
      hazard model. We allow unknown regression coefficients and time-dependent
      covariates in both models. The proposed estimators are maximizers of an exact
      correction to the joint log likelihood with the frailties eliminated as nuisance
      parameters, an idea that originated from correction of covariate measurement
      error in measurement error models. The corrected joint log likelihood is shown to
      be asymptotically concave and leads to consistent and asymptotically normal
      estimators. Unlike most published methods for joint modeling, the proposed
      estimation procedure does not rely on distributional assumptions of the
      frailties. The proposed method was studied in simulations and applied to a data
      set from the Hemodialysis Study.

PMID- 19173701
TI  - Bayesian inference for smoking cessation with a latent cure state.
AB  - We present a Bayesian approach to modeling dynamic smoking addiction behavior
      processes when cure is not directly observed due to censoring. Subject-specific
      probabilities model the stochastic transitions among three behavioral states:
      smoking, transient quitting, and permanent quitting (absorbent state). A
      multivariate normal distribution for random effects is used to account for the
      potential correlation among the subject-specific transition probabilities.
      Inference is conducted using a Bayesian framework via Markov chain Monte Carlo
      simulation. This framework provides various measures of subject-specific
      predictions, which are useful for policy-making, intervention development, and
      evaluation. Simulations are used to validate our Bayesian methodology and assess
      its frequentist properties. Our methods are motivated by, and applied to, the
      Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention study, a large (29,133
      individuals) longitudinal cohort study of smokers from Finland.

PMID- 19173702
TI  - Incorporating genotype uncertainty into mark-recapture-type models for estimating
      abundance using DNA samples.
AB  - Sampling DNA noninvasively has advantages for identifying animals for uses such
      as mark-recapture modeling that require unique identification of animals in
      samples. Although it is possible to generate large amounts of data from
      noninvasive sources of DNA, a challenge is overcoming genotyping errors that can
      lead to incorrect identification of individuals. A major source of error is
      allelic dropout, which is failure of DNA amplification at one or more loci. This
      has the effect of heterozygous individuals being scored as homozygotes at those
      loci as only one allele is detected. If errors go undetected and the genotypes
      are naively used in mark-recapture models, significant overestimates of
      population size can occur. To avoid this it is common to reject low-quality
      samples but this may lead to the elimination of large amounts of data. It is
      preferable to retain these low-quality samples as they still contain usable
      information in the form of partial genotypes. Rather than trying to minimize
      error or discarding error-prone samples we model dropout in our analysis. We
      describe a method based on data augmentation that allows us to model data from
      samples that include uncertain genotypes. Application is illustrated using data
      from the European badger (Meles meles).

PMID- 19173703
TI  - Bayesian hierarchical functional data analysis via contaminated informative
      priors.
AB  - A variety of flexible approaches have been proposed for functional data analysis,
      allowing both the mean curve and the distribution about the mean to be unknown.
      Such methods are most useful when there is limited prior information. Motivated
      by applications to modeling of temperature curves in the menstrual cycle, this
      article proposes a flexible approach for incorporating prior information in
      semiparametric Bayesian analyses of hierarchical functional data. The proposed
      approach is based on specifying the distribution of functions as a mixture of a
      parametric hierarchical model and a nonparametric contamination. The parametric
      component is chosen based on prior knowledge, while the contamination is
      characterized as a functional Dirichlet process. In the motivating application,
      the contamination component allows unanticipated curve shapes in unhealthy
      menstrual cycles. Methods are developed for posterior computation, and the
      approach is applied to data from a European fecundability study.

PMID- 19173704
TI  - Comparison of hierarchical Bayesian models for overdispersed count data using DIC
      and Bayes' factors.
AB  - When replicate count data are overdispersed, it is common practice to incorporate
      this extra-Poisson variability by including latent parameters at the observation
      level. For example, the negative binomial and Poisson-lognormal (PLN) models are
      obtained by using gamma and lognormal latent parameters, respectively. Several
      recent publications have employed the deviance information criterion (DIC) to
      choose between these two models, with the deviance defined using the Poisson
      likelihood that is obtained from conditioning on these latent parameters. The
      results herein show that this use of DIC is inappropriate. Instead, DIC was seen
      to perform well if calculated using likelihood that was marginalized at the group
      level by integrating out the observation-level latent parameters. This group
      level marginalization is explicit in the case of the negative binomial, but
      requires numerical integration for the PLN model. Similarly, DIC performed well
      to judge whether zero inflation was required when calculated using the group
      marginalized form of the zero-inflated likelihood. In the context of comparing
      multilevel hierarchical models, the top-level DIC was obtained using likelihood
      that was further marginalized by additional integration over the group-level
      latent parameters, and the marginal densities of the models were calculated for
      the purpose of providing Bayes' factors. The computational viability and
      interpretability of these different measures is considered.

PMID- 19173705
TI  - Improved detection of differentially expressed genes through incorporation of
      gene locations.
AB  - In determining differential expression in cDNA microarray experiments, the
      expression level of an individual gene is usually assumed to be independent of
      the expression levels of other genes, but many recent studies have shown that a
      gene's expression level tends to be similar to that of its neighbors on a
      chromosome, and differentially expressed (DE) genes are likely to form clusters
      of similar transcriptional activity along the chromosome. When modeled as a one
      dimensional spatial series, the expression level of genes on the same chromosome
      frequently exhibit significant spatial correlation, reflecting spatial patterns
      in transcription. By modeling these spatial correlations, we can obtain improved
      estimates of transcript levels. Here, we demonstrate the existence of spatial
      correlations in transcriptional activity in the Escherichia coli (E. coli)
      chromosome across more than 50 experimental conditions. Based on this finding, we
      propose a hierarchical Bayesian model that borrows information from neighboring
      genes to improve the estimation of the expression level of a given gene and hence
      the detection of DE genes. Furthermore, we extend the model to account for the
      circular structure of E. coli chromosome and the intergenetic distance between
      gene neighbors. The simulation studies and analysis of real data examples in E.
      coli and yeast Saccharomyces cerevisiae show that the proposed method outperforms
      the commonly used significant analysis of microarray (SAM) t-statistic in
      detecting DE genes.

PMID- 19173706
TI  - The 9p21 susceptibility locus for coronary artery disease and the severity of
      coronary atherosclerosis.
AB  - BACKGROUND: Case-control Genome-Wide Association Studies (GWAS) have identified
      single nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for
      coronary artery disease (CAD). The locus does not contain a clear candidate gene.
      Hence, the results of GWAS have raised an intense interest in delineating the
      basis for the observed association. We analyzed association of 4 SNPs at the 9p21
      locus with the severity and progression of coronary atherosclerosis, as
      determined by serial quantitative coronary angiograms (QCA) in the well
      characterized Lipoprotein Coronary Atherosclerosis Study (LCAS) population. The
      LCAS is a randomized placebo-control longitudinal follow-up study in patients
      with CAD conducted to test the effects of fluvastatin on progression or
      regression of coronary atherosclerosis. METHODS: Extensive plasma lipid levels
      were measured at the baseline and 2 1/2 years after randomization. Likewise
      serial QCA was performed at the baseline and upon completion of the study. We
      genotyped the population for 4 SNPs, previously identified as the susceptibility
      SNPs for CAD in GWAS, using fluorogenic 5' nuclease assays. We reconstructed the
      haplotypes using Phase 2, analyzed SNP and haplotype effects using the Thesias
      software as well as by the conventional statistical methods. RESULTS: Only
      Caucasians were included since they comprised 90% of the study population
      (332/371 with available DNA sample). The 4 SNPs at the 9p21 locus were in tight
      linkage disequilibrium, leading to 3 common haplotypes in the LCAS population. We
      found no significant association between quantitative indices of severity of
      coronary atherosclerosis, such as minimal lumen diameter and number of coronary
      lesions or occlusions and the 9p21 SNPs and haplotypes. Likewise, there was no
      association between quantitative indices of progression of coronary
      atherosclerosis and the SNPs or haplotypes. Similarly, we found no significant
      SNP or haplotype effect on severity and progression of coronary atherosclerosis.
      CONCLUSION: We conclude the 4 SNPs at the 9p21 locus analyzed in this study do
      not impart major effects on the severity or progression of coronary
      atherosclerosis. The effect size may be very modest or the observed association
      of the CAD with SNPs at the 9p21 locus in the case-control GWAS reflect
      involvement of vascular mechanisms not directly related to the severity or
      progression of coronary atherosclerosis.

PMID- 19173707
TI  - Conditional embryonic lethality to improve the sterile insect technique in
      Ceratitis capitata (Diptera: Tephritidae).
AB  - BACKGROUND: The sterile insect technique (SIT) is an environment-friendly method
      used in area-wide pest management of the Mediterranean fruit fly Ceratitis
      capitata (Wiedemann; Diptera: Tephritidae). Ionizing radiation used to generate
      reproductive sterility in the mass-reared populations before release leads to
      reduction of competitiveness. RESULTS: Here, we present a first alternative
      reproductive sterility system for medfly based on transgenic embryonic lethality.
      This system is dependent on newly isolated medfly promoter/enhancer elements of
      cellularization-specifically-expressed genes. These elements act differently in
      expression strength and their ability to drive lethal effector gene activation.
      Moreover, position effects strongly influence the efficiency of the system. Out
      of 60 combinations of driver and effector construct integrations, several lines
      resulted in larval and pupal lethality with one line showing complete embryonic
      lethality. This line was highly competitive to wildtype medfly in laboratory and
      field cage tests. CONCLUSION: The high competitiveness of the transgenic lines
      and the achieved 100% embryonic lethality causing reproductive sterility without
      the need of irradiation can improve the efficacy of operational medfly SIT
      programs.

PMID- 19173708
TI  - Bioinformatic flowchart and database to investigate the origins and diversity of
      clan AA peptidases.
AB  - BACKGROUND: Clan AA of aspartic peptidases relates the family of pepsin monomers
      evolutionarily with all dimeric peptidases encoded by eukaryotic LTR
      retroelements. Recent findings describing various pools of single-domain nonviral
      host peptidases, in prokaryotes and eukaryotes, indicate that the diversity of
      clan AA is larger than previously thought. The ensuing approach to investigate
      this enzyme group is by studying its phylogeny. However, clan AA is a difficult
      case to study due to the low similarity and different rates of evolution. This
      work is an ongoing attempt to investigate the different clan AA families to
      understand the cause of their diversity. RESULTS: In this paper, we describe in
      progress database and bioinformatic flowchart designed to characterize the clan
      AA protein domain based on all possible protein families through ancestral
      reconstructions, sequence logos, and hidden markov models (HMMs). The flowchart
      includes the characterization of a major consensus sequence based on 6 amino acid
      patterns with correspondence with Andreeva's model, the structural template
      describing the clan AA peptidase fold. The set of tools is work in progress we
      have organized in a database within the GyDB project, referred to as Clan AA
      Reference Database http://gydb.uv.es/gydb/phylogeny.php?tree=caard. CONCLUSION:
      The pre-existing classification combined with the evolutionary history of LTR
      retroelements permits a consistent taxonomical collection of sequence logos and
      HMMs. This set is useful for gene annotation but also a reference to evaluate the
      diversity of, and the relationships among, the different families. Comparisons
      among HMMs suggest a common ancestor for all dimeric clan AA peptidases that is
      halfway between single-domain nonviral peptidases and those coded by Ty3/Gypsy
      LTR retroelements. Sequence logos reveal how all clan AA families follow similar
      protein domain architecture related to the peptidase fold. In particular, each
      family nucleates a particular consensus motif in the sequence position related to
      the flap. The different motifs constitute a network where an alanine-asparagine
      like variable motif predominates, instead of the canonical flap of the HIV-1
      peptidase and closer relatives.

PMID- 19173709
TI  - A novel DNA-binding protein modulating methicillin resistance in Staphylococcus
      aureus.
AB  - BACKGROUND: Methicillin resistance in Staphylococcus aureus is conferred by the
      mecA-encoded penicillin-binding protein PBP2a. Additional genomic factors are
      also known to influence resistance levels in strain specific ways, although
      little is known about their contribution to resistance phenotypes in clinical
      isolates. Here we searched for novel proteins binding to the mec operator, in an
      attempt to identify new factor(s) controlling methicillin resistance phenotypes.
      RESULTS: Analysis of proteins binding to a DNA fragment containing the mec
      operator region identified a novel, putative helix-turn-helix DNA-binding
      protein, SA1665. Nonpolar deletion of SA1665, in heterogeneously methicillin
      resistant S. aureus (MRSA) of different genetic backgrounds, increased
      methicillin resistance levels in a strain dependent manner. This phenotype could
      be fully complemented by reintroducing SA1665 in trans. Northern and Western blot
      analyses, however, revealed that SA1665 had no visible influence on mecA
      transcription or amounts of PBP2a produced. CONCLUSION: SA1665 is a new
      chromosomal factor which influences methicillin resistance in MRSA. Although
      SA1665 bound to the mecA promoter region, it had no apparent influence on mecA
      transcription or translation, suggesting that this predicted DNA-binding protein
      modulates resistance indirectly, most likely through the control of other genomic
      factors which contribute to resistance.

PMID- 19173710
TI  - The effect of glutamine infusion on the inflammatory response and HSP70 during
      human experimental endotoxaemia.
AB  - INTRODUCTION: Glutamine supplementation has beneficial effects on morbidity and
      mortality in critically ill patients, possibly in part through an attenuation of
      the proinflammatory cytokine response and a stimulation of heat shock protein
      (HSP)70. We infused either alanine-glutamine or saline during endotoxin challenge
      and measured plasma cytokines and HSP70 protein expression. METHODS: This
      crossover study, conducted in eight healthy young men, was double-blind,
      randomized and placebo-controlled. It was performed on 2 trial days, separated by
      a 4-week washout period. The volunteers received an infusion of alanine-glutamine
      at a rate of 0.025 g/(kg body weight x hour) or saline for 10 hours. After 2
      hours, an intravenous bolus of Escherichia coli endotoxin (0.3 ng/kg) was
      administered. Blood samples were collected hourly for the following 8 hours.
      HSP70 protein content in isolated blood mononuclear cells (BMNCs) was measured by
      Western blotting. RESULTS: Plasma glutamine increased during alanine-glutamine
      infusion. Endotoxin reduced plasma glutamine during both trials, but plasma
      glutamine levels remained above baseline with alanine-glutamine supplementation.
      Endotoxin injection was associated with alterations in white blood cell and
      differential counts, tumour necrosis factor-alpha, IL-6, temperature and heart
      rate, but glutamine affected neither the endotoxin-induced change in these
      variables nor the expression of HSP70 in BMNCs. CONCLUSIONS: Endotoxin reduced
      plasma glutamine independently of alanine-glutamine infusion, but supplementation
      allows plasma levels to be maintained above baseline. Glutamine alters neither
      endotoxin-induced systemic inflammation nor early expression of HSP70 in BMNCs.
      TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT 00780520.

PMID- 19173712
TI  - Acute right iliac fossa pain: not always appendicitis or a caecal tumour: two
      case reports.
AB  - BACKGROUND: A solitary diverticulum of the caecum is a rare benign condition
      which was first described by Potier in 1912 1. Clinical symptoms are usually a
      manifestation of complications arising from inflammation, perforation or
      haemorrhage. Despite radiological imaging, a pre-operative diagnosis is
      infrequent. CASE PRESENTATION: We report two cases of right iliac fossa pain
      associated with a solitary caecal diverticulum. We discuss the clinical
      presentation, investigative modalities, and current therapeutic guidelines
      associated with this rare condition and highlight the difference from the more
      common conditions of appendicitis in the young and caecal neoplasms in the older
      patient. CONCLUSION: Complications of a solitary caecal diverticulum should be
      considered in the differential diagnosis of acute right lower quadrant pain. Mild
      caecal diverticulitis verified pre-operatively by radiological imaging or
      laparoscopically can be ameliorated by antibiotics alone. However, severe
      inflammation, perforation, haemorrhage or torsion necessitates a localised or
      radical resection. The presence of multiple diverticula, caecal phlegmon, or the
      inability to rule out an underlying caecal neoplasm warrants a right
      hemicolectomy.

PMID- 19173711
TI  - Consensus siRNA for inhibition of HCV genotype-4 replication.
AB  - BACKGROUND: HCV is circulating as a heterogeneous group of quasispecies. It has
      been addressed that siRNA can inhibit HCV replication in-vitro using HCV clone
      and/or replicon which have only one genotype. The current study was conducted to
      assess whether siRNA can inhibit different HCV genotypes with many quasispecies
      and to assess whether consensus siRNA have the same effect as regular siRNA.
      METHODS: We generated two chemically synthesized consensus siRNAs (Z3 and Z5)
      which cover most known HCV genotype sequences and quasispecies using Ambium
      system. Highly positive HCV patient's serum with nine quasispecies was
      transfected in-vitro to Huh-7 cell line which supports HCV genotype-4
      replication. siRNA (Z3&Z5) were transfected according to Qiagen Porta-lipid
      technique and subsequently cultured for eight days. HCV replication was monitored
      by RT-PCR for detection of plus and minus strands. Real-time PCR was used for
      quantification of HCV, whereas detection of the viral core protein was performed
      by western blot. RESULTS: HCV RNA levels decreased 18-fold (P = 0.001) and 25
      fold (P = 0.0005) in cells transfected with Z3 and Z5, respectively, on Day 2
      post transfection and continued for Day 3 by Z3 and Day 7 by Z5. Reduction of
      core protein expression was reported at Day 2 post Z3 siRNA transfection and at
      Day 1 post Z5 siRNA, which was persistent for Day 4 for the former and for Day 6
      for the latter. CONCLUSION: Consensus siRNA could be used as a new molecular
      target therapy to effectively inhibit HCV replication in the presence of more
      than one HCV quasispecies.

PMID- 19173713
TI  - Expression of somatostatin receptor subtypes in human thyroid tumors: the
      immunohistochemical and molecular biology (RT-PCR) investigation.
AB  - Human endocrine tumors often express the somatostatin receptors SSTR 1-5 with
      different intensity. It has been widely investigated their distribution in
      pituitary adenomas, brain tumors, adrenal tumors and neuroendocrine tumors in
      gastrointestinal tract (NET). Some of studies also concern the expression of
      SSTRs in thyroid tumors but they are mainly limited to parafollicular C cells -
      derived medullary thyroid carcinomas (MTC). Results of SSTR 1-5 detection in
      other thyroid pathologies like follicular adenomas and papillary cancers are
      still scarce and often controversial, depending of investigation method used. The
      aim of this study was to report the presence of all the 5 subtypes of SSTR
      (including 2A and 2B SSTR isoforms) in some surgically treated human thyroid
      tumors by means of immunohistochemistry and real-time PCR method and to correlate
      the results obtained with both techniques. SSTR 1 protein was expressed in 88.8%
      of investigated cases, SSTR 2A and 2B both in 44.4%, SSTR 3 in 55.5%, SSTR 4 in
      11.2% and SSTR 5 in 33.3%. SSTR 1 is the dominant form in the thyroid gland tumor
      and hyperplasia. We found positive confirmation of both methods in 88.8% for SSTR
      1, 2A, 3 subtypes, in 22.2% for SSTR 4 and in 100% for SSTR 5. It suggests that
      somatostatin multiligand analogs or selective SSTR 1 agonists may be used in
      thyroid tumors treatment.

PMID- 19173714
TI  - Sentinel lymph node biopsy for breast cancer using methylene blue dye manifests a
      short learning curve among experienced surgeons: a prospective tabular cumulative
      sum (CUSUM) analysis.
AB  - BACKGROUND: The benefits of sentinel lymph node biopsy (SLNB) for breast cancer
      patients with histologically negative axillary nodes, in whom axillary lymph node
      dissection (ALND) is thereby avoided, are now established. Low false negative
      rate, certainly with blue dye technique, mostly reflects the established high
      inherent accuracy of SLNB and low axillary nodal metastatic load (subject to
      patient selection). SLN identification rate is influenced by volume, injection
      site and choice of mapping agent, axillary nodal metastatic load, SLN location
      and skill at axillary dissection. Being more subject to technical failure, SLN
      identification seems to be a more reasonable variable for learning curve
      assessment than false negative rate. Methylene blue is as good an SLN mapping
      agent as Isosulfan blue and is much cheaper. Addition of radio-colloid mapping to
      blue dye does not achieve a sufficiently higher identification rate to justify
      the cost. Methylene blue is therefore the agent of choice for SLN mapping in
      developing countries. The American Society of Breast Surgeons recommends that,
      for competence, surgeons should perform 20 SLNB but admits that the learning
      curve with a standardized technique may be "much shorter". One appropriate remedy
      for this dilemma is to plot individual learning curves. METHODS: Using methylene
      blue dye, experienced breast surgeons performed SLNB in selected patients with
      breast cancer (primary tumor < 5 cm and clinically negative ipsilateral axilla).
      Intraoperative assessment and completion ALND were performed for standardization
      on the first 13 of 24 cases. SLN identification was plotted for each surgeon on a
      tabular cumulative sum (CUSUM) chart with sequential probability ratio test
      (SPRT) limits based on a target identification rate of 85%. RESULTS: The CUSUM
      plot crossed the SPRT limit line after 8 consecutive, positively identified SLN,
      signaling achievement of an acceptable level of competence. CONCLUSION: Tabular
      CUSUM charting, based on a justified choice of parameters, indicates that the
      learning curve for SLNB using methylene blue dye is completed after 8
      consecutive, positively identified SLN. CUSUM charting may be used to plot
      individual learning curves for trainee surgeons by applying a proxy parameter for
      failure in the presence of a mentor (such as failed SLN identification within 15
      minutes).

PMID- 19173716
TI  - Epicuticular lipids induce aggregation in Chagas disease vectors.
AB  - BACKGROUND: The triatomine bugs are vectors of the protozoan parasite Trypanosoma
      cruzi, the causative agent of Chagas disease. Aggregation behavior plays an
      important role in their survival by facilitating the location of refuges and
      cohesion of aggregates, helping to keep them safely assembled into shelters
      during daylight time, when they are vulnerable to predators. There are evidences
      that aggregation is mediated by thigmotaxis, by volatile cues from their faeces,
      and by hexane-extractable contact chemoreceptive signals from their cuticle
      surface. The epicuticular lipids of Triatoma infestans include a complex mixture
      of hydrocarbons, free and esterified fatty acids, alcohols, and sterols. RESULTS:
      We analyzed the response of T. infestans fifth instar nymphs after exposure to
      different amounts either of total epicuticular lipid extracts or individual lipid
      fractions. Assays were performed in a circular arena, employing a binary choice
      test with filter papers acting as aggregation attractive sites; papers were
      either impregnated with a hexane-extract of the total lipids, or lipid fraction;
      or with the solvent. Insects were significantly aggregated around papers
      impregnated with the epicuticular lipid extracts. Among the lipid fractions
      separately tested, only the free fatty acid fraction promoted significant bug
      aggregation. We also investigated the response to different amounts of selected
      fatty acid components of this fraction; receptiveness varied with the fatty acid
      chain length. No response was elicited by hexadecanoic acid (C16:0), the major
      fatty acid component. Octadecanoic acid (C18:0) showed a significant assembling
      effect in the concentration range tested (0.1 to 2 insect equivalents). The very
      long chain hexacosanoic acid (C26:0) was significantly attractant at low doses
      (</= 1 equivalent), although a repellent effect was observed at higher doses.
      CONCLUSION: The detection of contact aggregation pheromones has practical
      application in Chagas disease vector control. These data may be used to help
      design new tools against triatomine bugs.

PMID- 19173717
TI  - Highly efficient transduction of human plasmacytoid dendritic cells without
      phenotypic and functional maturation.
AB  - BACKGROUND: Gene modified dendritic cells (DC) are able to modulate DC functions
      and induce therapeutic immunity or tolerance in an antigen-specific manner. Among
      the different DC subsets, plasmacytoid DC (pDC) are well known for their ability
      to recognize and respond to a variety of viruses by secreting high levels of type
      I interferon. METHODS: We analyzed here, the transduction efficiency of a pDC
      cell line, GEN2.2, and of pDC derived from CD34+ progenitors, using lentiviral
      vectors (LV) pseudotyped with different envelope glycoproteins such as the
      vesicular stomatitis virus envelope (VSVG), the gibbon ape leukaemia virus
      envelope (GaLV) or the feline endogenous virus envelope (RD114). At the same
      time, we evaluated transgene expression (E-GFP reporter gene) under the control
      of different promoters. RESULTS: We found that efficient gene transfer into pDC
      can be achieved with VSVG-pseudotyped lentiviral vectors (LV) under the control
      of phoshoglycerate kinase (PGK) and elongation factor-1 (EF1alpha) promoters (28%
      to 90% of E-GFP+ cells, respectively) in the absence of phenotypic and functional
      maturation. Surprisingly, promoters (desmin or synthetic C5-12) described as
      muscle-specific and which drive gene expression in single strand AAV vectors in
      gene therapy protocols were very highly active in pDC using VSVG-LV. CONCLUSION:
      Taken together, our results indicate that LV vectors can serve to design pDC
      based vaccines in humans, and they are also useful in vitro to evaluate the
      immunogenicity of the vector preparations, and the specificity and safety of
      given promoters used in gene therapy protocols.

PMID- 19173719
TI  - A gene catalogue for post-diapause development of an anhydrobiotic arthropod
      Artemia franciscana.
AB  - BACKGROUND: Diapause is a reversible state of developmental suspension and found
      among diverse taxa, from plants to animals, including marsupials and some other
      mammals. Although previous work has accumulated ample data, the molecular
      mechanism underlying diapause and reactivation from it remain elusive. RESULTS:
      Using Artemia franciscana, a model organism to study the development of post
      diapause embryos in Arthropod, we sequenced random clones up to a total of 28,039
      ESTs from four cDNA libraries made from dehydrated cysts and three time points
      after rehydration/reactivation, which were assembled into 8,018 unigene clusters.
      We identified 324 differentially-expressed genes (DEGs, P < 0.05) based on
      pairwise comparisons of the four cDNA libraries. We identified a group of genes
      that are involved in an anti-water-deficit system, including proteases, protease
      inhibitors, heat shock proteins, and several novel members of the late
      embryogenesis abundant (LEA) protein family. In addition, we classified most of
      the up-regulated genes after cyst reactivation into metabolism, biosynthesis,
      transcription, and translation, and this result is consistent with the rapid
      development of the embryo. Some of the specific expressions of DEGs were
      confirmed experimentally based on quantitative real-time PCR. CONCLUSION: We
      found that the first 5-hour period after rehydration is most important for
      embryonic reactivation of Artemia. As the total number of expressed genes
      increases significantly, the majority of DEGs were also identified in this
      period, including a group of water-deficient-induced genes. A group of genes with
      similar functions have been described in plant seeds; for instance, one of the
      novel LEA members shares ~70% amino-acid identity with an Arabidopsis EM
      (embryonic abundant) protein, the closest animal relative to plant LEA families
      identified thus far. Our findings also suggested that not only nutrition, but
      also mRNAs are produced and stored during cyst formation to support rapid
      development after reactivation.

PMID- 19173718
TI  - Use of folding modulators to improve heterologous protein production in
      Escherichia coli.
AB  - Despite the fundamental importance of E. coli in the manufacture of a wide range
      of biotechnological and biomedical products, extensive process and/or target
      optimisation is routinely required in order to achieve functional yields in
      excess of low mg/l levels. Molecular chaperones and folding catalysts appear to
      present a panacea for problems of heterologous protein folding in the organism,
      due largely to their broad substrate range compared with, e.g., protein-specific
      mutagenesis approaches. Painstaking investigation of chaperone overproduction
      has, however, met with mixed - and largely unpredictable - results to date. The
      past 5 years have nevertheless seen an explosion in interest in exploiting the
      native folding modulators of E. coli, and particularly cocktails thereof, driven
      largely by the availability of plasmid systems that facilitate simultaneous, non
      rational screening of multiple chaperones during recombinant protein expression.
      As interest in using E. coli to produce recombinant membrane proteins and even
      glycoproteins grows, approaches to reduce aggregation, delay host cell lysis and
      optimise expression of difficult-to-express recombinant proteins will become even
      more critical over the coming years. In this review, we critically evaluate the
      performance of molecular chaperones and folding catalysts native to E. coli in
      improving functional production of heterologous proteins in the bacterium and we
      discuss how they might best be exploited to provide increased amounts of
      correctly-folded, active protein for biochemical and biophysical studies.

PMID- 19173720
TI  - Low frequency of CD4+CD25+ Treg in SLE patients: a heritable trait associated
      with CTLA4 and TGFbeta gene variants.
AB  - BACKGROUND: CD4+CD25+ regulatory T cells play an essential role in maintaining
      immune homeostasis and preventing autoimmunity. Therefore, defects in Treg
      development, maintenance or function have been associated with several human
      autoimmune diseases including Systemic Lupus Erythematosus (SLE), a systemic
      autoimmune disease characterized by loss of tolerance to nuclear components and
      significantly more frequent in females. RESULTS: To investigate the involvement
      of Treg in SLE pathogenesis, we determined the frequency of CD4+CD25+CD45RO+ T
      cells, which encompass the majority of Treg activity, in the PBMC of 148 SLE
      patients (76 patients were part of 54 families), 166 relatives and 117 controls.
      SLE patients and their relatives were recruited in several Portuguese hospitals
      and through the Portuguese Lupus Association. Control individuals were blood
      donors recruited from several regional blood donor centers. Treg frequency was
      significantly lower in SLE patients than healthy controls (z = -6.161, P <
      0.00001) and intermediate in the relatives' group. Remarkably, this T cell subset
      was also lower in females, most strikingly in the control population (z = 4.121,
      P < 0.001). We further ascertained that the decreased frequency of Treg in SLE
      patients resulted from the specific reduction of bona fide FOXP3+CD4+CD25+ Treg.
      Treg frequency was negatively correlated with SLE activity index (SLEDAI) and
      titers of serum anti-dsDNA antibodies. Both Treg frequency and disease activity
      were modulated by IVIg treatment in a documented SLE case. The segregation of
      Treg frequency within the SLE families was indicative of a genetic trait.
      Candidate gene analysis revealed that specific variants of CTLA4 and TGFbeta were
      associated with the decreased frequency of Treg in PBMC, while FOXP3 gene
      variants were associated with affection status, but not with Treg frequency.
      CONCLUSION: SLE patients have impaired Treg production or maintenance, a trait
      strongly associated with SLE disease activity and autoantibody titers, and
      possibly resulting from the inability to convert FOXP3+CD25- into FOXP3+CD25+ T
      cells. Treg frequency is highly heritable within SLE families, with specific
      variants of the CTLA4 and TGFbeta genes contributing to this trait, while FOXP3
      contributes to SLE through mechanisms not involving a modulation of Treg
      frequency. These findings establish that the genetic components in SLE
      pathogenesis include genes related to Treg generation or maintenance.

PMID- 19173722
TI  - Hepatitis following famotidine: a case report.
AB  - H2 receptor antagonists can rarely cause idiosyncratic drug reactions leading to
      acute hepatitis. Famotidine, however, is considered a relatively safe drug with
      regards to hepatotoxicity. We report a case of a 47 year old male with a history
      of hepatitis C who developed acute hepatitis on the third day of hospitalization
      with a dramatic rise in his liver enzymes from normal values at the time of
      admission. The acute rise in liver enzymes made us consider an adverse drug
      reaction and famotidine was discontinued. Subsequently his liver enzymes came
      back to normal in seven days. Thus, physicians should consider famotidine induced
      hepatitis as a possible etiology of acute liver dysfunction.

PMID- 19173721
TI  - Secondary prevention of heart disease--knowledge among cardiologists and omega-3
      (omega-3) fatty acid prescribing behaviors in Karachi, Pakistan.
AB  - BACKGROUND: The use of omega-3 fatty acids is a currently proven strategy for
      secondary prevention of heart disease. The prescription practices for this
      important nutraceutical is not currently known. It is imperative to assess the
      knowledge of cardiologists regarding the benefits of omega-3 fatty acids and to
      determine the frequency of its prescription. The aim of the study was to
      determine the practices and associations of dietary fish prescribing among
      cardiologists of Karachi and to assess their knowledge of fish oil
      supplementation and attitudes toward dietary practices. METHODS: A cross
      sectional survey was conducted during the period of January to March, 2008. A
      self report questionnaire was employed. All practicing cardiologists of Karachi
      were included in the study. Multiple logistic regression analysis was performed
      to determine the independent factors associated with high fish prescribers.
      RESULTS: The sample comprised of a total of 163 cardiologists practicing in
      Karachi, Pakistan. Most (73.6%) of the cardiologists fell in the age range of 28
      45 years and were male (90.8%). High fish prescribers only comprised 36.2% of the
      respondents. After adjusting for age and gender, multivariate analysis revealed
      that only the variable of knowledge about fish oil's role in reducing sudden
      cardiac death was independently associated with high fish prescribers OR = 6.38
      [95% CI 2.58-15.78]. CONCLUSION: The level of knowledge about the benefits of
      omega-3 fatty acids is high and the cardiologists harbor a favorable attitude
      towards dispensing dietary fish advice. However, the prescription practices are
      less than optimal and not concordant with recommendations of organisations such
      as the American Heart Association and National Heart Foundation of Australia. The
      knowledge of prevention of sudden cardiac death in CVD patients has been
      identified as an important predictor of high fish prescription. This particular
      life-saving property of omega-3 fatty acids should be the focus of any
      implemented educational strategy targeted to improve secondary CVD prevention via
      omega-3 fatty acid supplementation.

PMID- 19173723
TI  - Activation of mRNA translation by phage protein and low temperature: the case of
      Lactococcus lactis abortive infection system AbiD1.
AB  - BACKGROUND: Abortive infection (Abi) mechanisms comprise numerous strategies
      developed by bacteria to avoid being killed by bacteriophage (phage). Escherichia
      coli Abis are considered as mediators of programmed cell death, which is induced
      by infecting phage. Abis were also proposed to be stress response elements, but
      no environmental activation signals have yet been identified. Abis are widespread
      in Lactococcus lactis, but regulation of their expression remains an open
      question. We previously showed that development of AbiD1 abortive infection
      against phage bIL66 depends on orf1, which is expressed in mid-infection.
      However, molecular basis for this activation remains unclear. RESULTS: In non
      infected AbiD1+ cells, specific abiD1 mRNA is unstable and present in low
      amounts. It does not increase during abortive infection of sensitive phage.
      Protein synthesis directed by the abiD1 translation initiation region is also
      inefficient. The presence of the phage orf1 gene, but not its mutant AbiD1R
      allele, strongly increases abiD1 translation efficiency. Interestingly, cell
      growth at low temperature also activates translation of abiD1 mRNA and
      consequently the AbiD1 phenotype, and occurs independently of phage infection.
      There is no synergism between the two abiD1 inducers. Purified Orf1 protein binds
      mRNAs containing a secondary structure motif, identified within the translation
      initiation regions of abiD1, the mid-infection phage bIL66 M-operon, and the L.
      lactis osmC gene. CONCLUSION: Expression of the abiD1 gene and consequently AbiD1
      phenotype is specifically translationally activated by the phage Orf1 protein.
      The loss of ability to activate translation of abiD1 mRNA determines the
      molecular basis for phage resistance to AbiD1. We show for the first time that
      temperature downshift also activates abortive infection by activation of abiD1
      mRNA translation.

PMID- 19173724
TI  - A qualitative study of patients' views on quality of primary care consultations
      in Hong Kong and comparison with the UK CARE Measure.
AB  - BACKGROUND: Patients' priorities and views on quality care are well-documented in
      Western countries but there is a dearth of research in this area in the East. The
      aim of the present study was to explore Chinese patients' views on quality of
      primary care consultations in Hong Kong and to compare these with the items in
      the CARE measure (a process measure of consultation quality widely used in the
      UK) in order to assess the potential utility of the CARE measure in a Chinese
      population. METHODS: Individual semi-structured interviews were conducted on 21
      adult patients from 3 different primary care clinics (a public primary healthcare
      clinic, a University health centre, and a private family physician's clinic).
      Topics discussed included expectations, experiences, and views about quality of
      medical consultations. Interviews were typed verbatim, and a thematic approach
      was taken to identify key issues. These identified issues were then compared with
      the ten CARE measure items, using a CARE framework: Connecting (Care Measure
      items 1-3), Assessing (item 4), Responding (items 5,6), and Empowering (items 7
      10). RESULTS: Patients judged doctors in terms of both the process of the
      consultation and the perceived outcomes. Themes identified that related to the
      interpersonal process of the consultation fitted well under the CARE framework;
      Connecting and communicating (18/21 patients), Assessing holistically (10/21
      patients), Responding (18/21 patients) and Empowering (19/21 patients). Patients
      from the public clinic, who were generally of lower socio-economic status, were
      least likely to expect holistic care or empowerment. Two-thirds of patients also
      judged doctors on whether they performed an adequate physical examination, and
      three-quarters on the later outcomes of consultation (in terms of relief or cure
      and/or side-effects of prescribed drugs). CONCLUSION: These findings suggest that
      Chinese patients in Hong Kong value engaged, empathic primary care doctors and
      judge the quality of consultations largely on these human skills and the
      attitudes and values that underpin them, as well as on the perceived outcomes of
      treatment. The match between themes relating to consultation process and the CARE
      Measure items suggests utility of this measure in this population, but further
      quantitative validation is required.

PMID- 19173725
TI  - An analysis of lecture video utilization in undergraduate medical education:
      associations with performance in the courses.
AB  - BACKGROUND: Increasing numbers of medical schools are providing videos of
      lectures to their students. This study sought to analyze utilization of lecture
      videos by medical students in their basic science courses and to determine if
      student utilization was associated with performance on exams. METHODS: Streaming
      videos of lectures (n = 149) to first year and second year medical students (n =
      284) were made available through a password-protected server. Server logs were
      analyzed over a 10-week period for both classes. For each lecture, the logs
      recorded time and location from which students accessed the file. A survey was
      administered at the end of the courses to obtain additional information about
      student use of the videos. RESULTS: There was a wide disparity in the level of
      use of lecture videos by medical students with the majority of students accessing
      the lecture videos sparingly (60% of the students viewed less than 10% of the
      available videos. The anonymous student survey revealed that students tended to
      view the videos by themselves from home during weekends and prior to exams.
      Students who accessed lecture videos more frequently had significantly (p <
      0.002) lower exam scores. CONCLUSION: We conclude that videos of lectures are
      used by relatively few medical students and that individual use of videos is
      associated with the degree to which students are having difficulty with the
      subject matter.

PMID- 19173726
TI  - Molecular characterization of Mycobacterium bovis strains isolated from cattle
      slaughtered at two abattoirs in Algeria.
AB  - BACKGROUND: Bovine Tuberculosis is prevalent in Algeria despite governmental
      attempts to control the disease. The objective of this study was to conduct, for
      the first time, molecular characterization of a population sample of
      Mycobacterium bovis strains isolated from slaughter cattle in Algeria. Between
      August and November 2007, 7250 animals were consecutively screened at the
      abattoirs of Algiers and Blida. In 260 animals, gross visible granulomatous
      lesions were detected and put into culture. Bacterial isolates were subsequently
      analysed by molecular methods. RESULTS: Altogether, 101 bacterial strains from
      100 animals were subjected to molecular characterization. M. bovis was isolated
      from 88 animals. Other bacteria isolated included one strain of M. caprae, four
      Rhodococcus equi strains, three Non-tuberculous Mycobacteria (NTM) and five
      strains of other bacterial species. The M. bovis strains isolated showed 22
      different spoligotype patterns; four of them had not been previously reported.
      The majority of M. bovis strains (89%) showed spoligotype patterns that were
      previously observed in strains from European cattle. Variable Number of Tandem
      Repeat (VNTR) typing supported a link between M. bovis strains from Algeria and
      France. One spoligotype pattern has also been shown to be frequent in M. bovis
      strains from Mali although the VNTR pattern of the Algerian strains differed from
      the Malian strains. CONCLUSION: M. bovis infections account for a high amount of
      granulomatous lesions detected in Algerian slaughter cattle during standard meat
      inspection at Algiers and Blida abattoir. Molecular typing results suggested a
      link between Algerian and European strains of M. bovis.

PMID- 19173727
TI  - Primary hepatic carcinoid tumor: a case report and review of the literature.
AB  - BACKGROUND: Primary hepatic carcinoid tumor (PHCT) is very rare and difficult to
      diagnose before biopsy or operation. We report a patient with a small PHCT and
      review cases in the literature. CASE PRESENTATION: A 48-year-old Chinese female
      with underlying hepatitis B virus (HBV) infection was found to have a low echoic
      hepatic nodule by abdominal ultrasound. Tumor markers were negative. Dynamic
      liver computed tomography scans showed enhancement of the nodule in the arterial
      phase and early washout in the portal phase. Hepatocellular carcinoma (HCC) was
      considered based on the image findings and underlying HBV infection. However, the
      tumor biopsy revealed a malignant neoplasm that originating from neuroendocrine
      cells. Pre-operative and intra-operative investigations for the possible other
      origin of carcinoid tumor were negative, so PHCT was confirmed. CONCLUSION: A
      small and asymptomatic PHCT is extremely rare. PHCT should be one of the
      differential diagnoses in patients with small hepatic tumor, even in regions with
      high prevalence of HBV infection and HCC. Pre-operative biopsy is necessary to
      avoid misdiagnosis even when HCC is highly suspected clinically.

PMID- 19173728
TI  - A giant colonic diverticulum presenting as a 'phantom mass': a case report.
AB  - INTRODUCTION: Diverticulosis coli is the most common disease of the colon in
      Western countries. Giant colonic diverticulum, defined as a colonic diverticulum
      measuring 4 cm in size or larger, represents an unusual manifestation of this
      common clinical entity. CASE PRESENTATION: A 68-year-old Caucasian British woman
      with a history of intermittent lower abdominal mass, leg swelling and focal
      neurological symptoms underwent extensive non-diagnostic investigations over a
      significant period under a number of disciplines. The reason for a diagnosis
      being elusive in part related to the fact that the mass was never found on
      clinical and ultrasound examination. As a result, the patient's validity was
      questioned. Ultimately, this 'phantom-mass' was diagnosed as a giant colonic
      diverticulum causing intermittent compression of the iliac vein and obturator
      nerve. CONCLUSION: Intermittent compression of the iliac vein and the obturator
      nerve by a colonic diverticulum has not previously been reported. A giant colonic
      diverticulum presenting as an intermittent mass is very rare. This case also
      illustrates two factors. First, the patient is often right. Second, the optimal
      mode of investigation for any proven or described abdominal mass with referred
      symptoms is cross-sectional imaging, typically a computed tomography scan,
      irrespective whether the mass or symptoms are constant or intermittent.

PMID- 19173715
TI  - A comprehensive overview of radioguided surgery using gamma detection probe
      technology.
AB  - The concept of radioguided surgery, which was first developed some 60 years ago,
      involves the use of a radiation detection probe system for the intraoperative
      detection of radionuclides. The use of gamma detection probe technology in
      radioguided surgery has tremendously expanded and has evolved into what is now
      considered an established discipline within the practice of surgery,
      revolutionizing the surgical management of many malignancies, including breast
      cancer, melanoma, and colorectal cancer, as well as the surgical management of
      parathyroid disease. The impact of radioguided surgery on the surgical management
      of cancer patients includes providing vital and real-time information to the
      surgeon regarding the location and extent of disease, as well as regarding the
      assessment of surgical resection margins. Additionally, it has allowed the
      surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic
      procedures, while still maintaining maximum benefit to the cancer patient. In the
      current review, we have attempted to comprehensively evaluate the history,
      technical aspects, and clinical applications of radioguided surgery using gamma
      detection probe technology.

PMID- 19173729
TI  - Combinatorial effects of environmental parameters on transcriptional regulation
      in Saccharomyces cerevisiae: a quantitative analysis of a compendium of chemostat
      based transcriptome data.
AB  - BACKGROUND: Microorganisms adapt their transcriptome by integrating multiple
      chemical and physical signals from their environment. Shake-flask cultivation
      does not allow precise manipulation of individual culture parameters and
      therefore precludes a quantitative analysis of the (combinatorial) influence of
      these parameters on transcriptional regulation. Steady-state chemostat cultures,
      which do enable accurate control, measurement and manipulation of individual
      cultivation parameters (e.g. specific growth rate, temperature, identity of the
      growth-limiting nutrient) appear to provide a promising experimental platform for
      such a combinatorial analysis. RESULTS: A microarray compendium of 170 steady
      state chemostat cultures of the yeast Saccharomyces cerevisiae is presented and
      analyzed. The 170 microarrays encompass 55 unique conditions, which can be
      characterized by the combined settings of 10 different cultivation parameters. By
      applying a regression model to assess the impact of (combinations of) cultivation
      parameters on the transcriptome, most S. cerevisiae genes were shown to be
      influenced by multiple cultivation parameters, and in many cases by combinatorial
      effects of cultivation parameters. The inclusion of these combinatorial effects
      in the regression model led to higher explained variance of the gene expression
      patterns and resulted in higher function enrichment in subsequent analysis. We
      further demonstrate the usefulness of the compendium and regression analysis for
      interpretation of shake-flask-based transcriptome studies and for guiding
      functional analysis of (uncharacterized) genes and pathways. CONCLUSION: Modeling
      the combinatorial effects of environmental parameters on the transcriptome is
      crucial for understanding transcriptional regulation. Chemostat cultivation
      offers a powerful tool for such an approach.

PMID- 19173730
TI  - Characterization of the time course of changes of the evoked electrical activity
      in a model of a chemically-induced neuronal plasticity.
AB  - BACKGROUND: Neuronal plasticity is initiated by transient elevations of neuronal
      networks activity leading to changes of synaptic properties and providing the
      basis for memory and learning 1. An increase of electrical activity can be caused
      by electrical stimulation 2 or by pharmacological manipulations: elevation of
      extracellular K+ 3, blockage of inhibitory pathways 4 or by an increase of second
      messengers intracellular concentrations 5. Neuronal plasticity is mediated by
      several biochemical pathways leading to the modulation of synaptic strength,
      density of ionic channels and morphological changes of neuronal arborisation 6.
      On a time scale of a few minutes, neuronal plasticity is mediated by local
      protein trafficking 7 while, in order to sustain modifications beyond 2-3 h,
      changes of gene expression are required 8. FINDINGS: In the present manuscript we
      analysed the time course of changes of the evoked electrical activity during
      neuronal plasticity and we correlated it with a transcriptional analysis of the
      underlying changes of gene expression. Our investigation shows that treatment for
      30 min. with the GABAA receptor antagonist gabazine (GabT) causes a potentiation
      of the evoked electrical activity occurring 2-4 hours after GabT and the
      concomitant up-regulation of 342 genes. Inhibition of the ERK1/2 pathway reduced
      but did not abolish the potentiation of the evoked response caused by GabT. In
      fact not all the genes analysed were blocked by ERK1/2 inhibitors. CONCLUSION:
      These results are in agreement with the notion that neuronal plasticity is
      mediated by several distinct pathways working in unison.

PMID- 19173731
TI  - One ancestor for two codes viewed from the perspective of two complementary modes
      of tRNA aminoacylation.
AB  - BACKGROUND: The genetic code is brought into action by 20 aminoacyl-tRNA
      synthetases. These enzymes are evenly divided into two classes (I and II) that
      recognize tRNAs from the minor and major groove sides of the acceptor stem,
      respectively. We have reported recently that: (1) ribozymic precursors of the
      synthetases seem to have used the same two sterically mirror modes of tRNA
      recognition, (2) having these two modes might have helped in preventing erroneous
      aminoacylation of ancestral tRNAs with complementary anticodons, yet (3) the risk
      of confusion for the presumably earliest pairs of complementarily encoded amino
      acids had little to do with anticodons. Accordingly, in this communication we
      focus on the acceptor stem. RESULTS: Our main result is the emergence of a
      palindrome structure for the acceptor stem's common ancestor, reconstructed from
      the phylogenetic trees of Bacteria, Archaea and Eukarya. In parallel, for pairs
      of ancestral tRNAs with complementary anticodons, we present updated evidence of
      concerted complementarity of the second bases in the acceptor stems. These two
      results suggest that the first pairs of "complementary" amino acids that were
      engaged in primordial coding, such as Gly and Ala, could have avoided erroneous
      aminoacylation if and only if the acceptor stems of their adaptors were
      recognized from the same, major groove, side. The class II protein synthetases
      then inherited this "primary preference" from isofunctional ribozymes.
      CONCLUSION: Taken together, our results support the hypothesis that the genetic
      code per se (the one associated with the anticodons) and the operational code of
      aminoacylation (associated with the acceptor) diverged from a common ancestor
      that probably began developing before translation. The primordial advantage of
      linking some amino acids (most likely glycine and alanine) to the ancestral
      acceptor stem may have been selective retention in a protocell surrounded by a
      leaky membrane for use in nucleotide and coenzyme synthesis. Such acceptor stems
      (as cofactors) thus transferred amino acids as groups for biosynthesis. Later,
      with the advent of an anticodon loop, some amino acids (such as aspartic acid,
      histidine, arginine) assumed a catalytic role while bound to such extended
      adaptors, in line with the original coding coenzyme handle (CCH) hypothesis.

PMID- 19173732
TI  - Profiling RE1/REST-mediated histone modifications in the human genome.
AB  - BACKGROUND: The transcriptional repressor REST (RE1 silencing transcription
      factor, also called NRSF for neuron-restrictive silencing factor) binds to a
      conserved RE1 motif and represses many neuronal genes in non-neuronal cells. This
      transcriptional regulation is transacted by several nucleosome-modifying enzymes
      recruited by REST to RE1 sites, including histone deacetylases (for example,
      HDAC1/2), demethylases (for example, LSD1), and methyltransferases (for example,
      G9a). RESULTS: We have investigated a panel of 38 histone modifications by ChIP
      Seq analysis for REST-mediated changes. Our study reveals a systematic decline of
      histone acetylations modulated by the association of RE1 with REST (RE1/REST). By
      contrast, alteration of histone methylations is more heterogeneous, with some
      methylations increased (for example, H3K27me3, and H3K9me2/3) and others
      decreased (for example, H3K4me, and H3K9me1). Furthermore, the observation of
      such trends of histone modifications in upregulated genes demonstrates
      convincingly that these changes are not determined by gene expression but are
      RE1/REST dependent. The outcomes of REST binding to canonical and non-canonical
      RE1 sites were nearly identical. Our analyses have also provided the first direct
      evidence that REST induces context-specific nucleosome repositioning, and
      furthermore demonstrate that REST-mediated histone modifications correlate with
      the affinity of RE1 motifs and the abundance of RE1-bound REST molecules.
      CONCLUSIONS: Our findings indicate that the landscape of REST-mediated chromatin
      remodeling is dynamic and complex, with novel histone modifying enzymes and
      mechanisms yet to be elucidated. Our results should provide valuable insights for
      selecting the most informative histone marks for investigating the mechanisms and
      the consequences of REST modulated nucleosome remodeling in both neural and non
      neural systems.

PMID- 19173733
TI  - Brucella bacteremia in a recipient of an allogeneic hematopoietic stem cell
      transplant: a case report.
AB  - BACKGROUND: Brucellosis is an important cause of morbidity and mortality in
      patients living in areas that are endemic for the infection. CASE PRESENTATION: A
      20 years old Saudi male was diagnosed to have severe aplastic anemia at King
      Faisal Specialist Hospital and Research Centre in Riyadh in April 2006. One
      hundred and twelve days following his successful allogeneic hematopoietic stem
      cell transplant, he presented with pyrexia in addition to neutropenia and mild
      thrombocytopenia. Brucella serology was strongly positive and blood cultures grew
      Brucella melitensis. The bacteremic episode of brucellosis was successfully
      treated with streptomycin, doxycyclin and ciprofloxacin at the outpatient clinic.
      To our knowledge, this is the first case of a naturally occurring Brucella
      infection complicated by Brucella bacteremia in a recipient of hematopoietic stem
      cell transplant. CONCLUSION: Brucellosis may cause systemic infections,
      complicated bacteremias and serious morbidity in immunocompromised patients
      living in countries that are endemic for the infection. It should be considered
      as a possible cause of fever and pancytopenia in hematopoietic stem cell
      transplant recipients living in these geographical locations. Nevertheless, the
      infection is curable provided the diagnosis is made early and an appropriate
      antimicrobial therapy is promptly initiated.

PMID- 19173734
TI  - Ultrastructure and molecular phylogeny of Calkinsia aureus: cellular identity of
      a novel clade of deep-sea euglenozoans with epibiotic bacteria.
AB  - BACKGROUND: The Euglenozoa is a large group of eukaryotic flagellates with
      diverse modes of nutrition. The group consists of three main subclades -
      euglenids, kinetoplastids and diplonemids--that have been confirmed with both
      molecular phylogenetic analyses and a combination of shared ultrastructural
      characteristics. Several poorly understood lineages of putative euglenozoans live
      in anoxic environments, such as Calkinsia aureus, and have yet to be
      characterized at the molecular and ultrastructural levels. Improved understanding
      of these lineages is expected to shed considerable light onto the ultrastructure
      of prokaryote-eukaryote symbioses and the associated cellular innovations found
      within the Euglenozoa and beyond. RESULTS: We collected Calkinsia aureus from
      core samples taken from the low-oxygen seafloor of the Santa Barbara Basin (580 -
      592 m depth), California. These biflagellates were distinctively orange in color
      and covered with a dense array of elongated epibiotic bacteria. Serial TEM
      sections through individually prepared cells demonstrated that C. aureus shares
      derived ultrastructural features with other members of the Euglenozoa (e.g. the
      same paraxonemal rods, microtubular root system and extrusomes). However, C.
      aureus also possessed several novel ultrastructural systems, such as modified
      mitochondria (i.e. hydrogenosome-like), an "extrusomal pocket", a highly
      organized extracellular matrix beneath epibiotic bacteria and a complex flagellar
      transition zone. Molecular phylogenies inferred from SSU rDNA sequences
      demonstrated that C. aureus grouped strongly within the Euglenozoa and with
      several environmental sequences taken from low-oxygen sediments in various
      locations around the world. CONCLUSION: Calkinsia aureus possesses all of the
      synapomorphies for the Euglenozoa, but lacks traits that are specific to any of
      the three previously recognized euglenozoan subgroups. Molecular phylogenetic
      analyses of C. aureus demonstrate that this lineage is a member of a novel
      euglenozoan subclade consisting of uncharacterized cells living in low-oxygen
      environments. Our ultrastructural description of C. aureus establishes the
      cellular identity of a fourth group of euglenozoans, referred to as the
      "Symbiontida".

PMID- 19173735
TI  - The tep1 gene of Sinorhizobium meliloti coding for a putative transmembrane
      efflux protein and N-acetyl glucosamine affect nod gene expression and nodulation
      of alfalfa plants.
AB  - BACKGROUND: Soil bacteria collectively known as Rhizobium, characterized by their
      ability to establish beneficial symbiosis with legumes, share several common
      characteristics with pathogenic bacteria when infecting the host plant. Recently,
      it was demonstrated that a fadD mutant of Sinorhizobium meliloti is altered in
      the control of swarming, a type of co-ordinated movement previously associated
      with pathogenicity, and is also impaired in nodulation efficiency on alfalfa
      roots. In the phytopathogen Xanthomonas campestris, a fadD homolog (rpfB) forms
      part of a cluster of genes involved in the regulation of pathogenicity factors.
      In this work, we have investigated the role in swarming and symbiosis of
      SMc02161, a S. meliloti fadD-linked gene. RESULTS: The SMc02161 locus in S.
      meliloti shows similarities with members of the Major Facilitator Superfamily
      (MFS) of transporters. A S. meliloti null-mutant shows increased sensitivity to
      chloramphenicol. This indication led us to rename the locus tep1 for
      transmembrane efflux protein. The lack of tep1 does not affect the appearance of
      swarming motility. Interestingly, nodule formation efficiency on alfalfa plants
      is improved in the tep1 mutant during the first days of the interaction though
      nod gene expression is lower than in the wild type strain. Curiously, a nodC
      mutation or the addition of N-acetyl glucosamine to the wild type strain lead to
      similar reductions in nod gene expression as in the tep1 mutant. Moreover,
      aminosugar precursors of Nod factors inhibit nodulation. CONCLUSION: tep1
      putatively encodes a transmembrane protein which can confer chloramphenicol
      resistance in S. meliloti by expelling the antibiotic outside the bacteria. The
      improved nodulation of alfalfa but reduced nod gene expression observed in the
      tep1 mutant suggests that Tep1 transports compounds which influence nodulation.
      In contrast to Bradyrhizobium japonicum, we show that in S. meliloti there is no
      feedback regulation of nodulation genes. Moreover, the Nod factor precursor, N
      acetyl glucosamine reduces nod gene expression and nodulation efficiency when
      present at millimolar concentrations. A role for Tep1 in the efflux of Nod factor
      precursors could explain the phenotypes associated with tep1 inactivation.

PMID- 19173736
TI  - Tamoxifen induces pleiotrophic changes in mammary stroma resulting in
      extracellular matrix that suppresses transformed phenotypes.
AB  - INTRODUCTION: The functional unit of the mammary gland has been defined as the
      epithelial cell plus its microenvironment, a hypothesis that predicts changes in
      epithelial cell function will be accompanied by concurrent changes in mammary
      stroma. To test this hypothesis, the question was addressed of whether mammary
      stroma is functionally altered by the anti-oestrogen drug tamoxifen. METHODS:
      Forty female rats at 70 days of age were randomised to two groups of 20 and
      treated with 1.0 mg/kg tamoxifen or vehicle subcutaneously daily for 30 days,
      followed by a three-day wash out period. Mammary tissue was harvested and effects
      of tamoxifen on mammary epithelium and stroma determined. RESULTS: As expected,
      tamoxifen suppressed mammary alveolar development and mammary epithelial cell
      proliferation. Primary mammary fibroblasts isolated from tamoxifen-treated rats
      displayed a three-fold decrease in motility and incorporated less fibronectin in
      their substratum in comparison to control fibroblasts; attributes indicative of
      fibroblast quiescence. Immunohistochemistry analysis of CD68, a macrophage
      lysosomal marker, demonstrated a reduction in macrophage infiltration in mammary
      glands of tamoxifen-treated rats. Proteomic analyses by mass spectrometry
      identified several extracellular matrix (ECM) proteins with expression levels
      with tamoxifen treatment that were validated by Western blot. Mammary tissue from
      tamoxifen-treated rats had decreased fibronectin and increased collagen 1 levels.
      Further, ECM proteolysis was reduced in tamoxifen-treated rats as detected by
      reductions in fibronectin, laminin 1, laminin 5 and collagen 1 cleavage
      fragments. Consistent with suppression in ECM proteolysis with tamoxifen
      treatment, matrix metalloproteinase-2 levels and activity were decreased.
      Biochemically extracted mammary ECM from tamoxifen-treated rats suppressed in
      vitro macrophage motility, which was rescued by the addition of proteolysed
      collagen or fibronectin. Mammary ECM from tamoxifen-treated rats also suppressed
      breast tumour cell motility, invasion and haptotaxis, reduced organoid size in 3
      dimensional culture and blocked tumour promotion in an orthotopic xenograft
      model; effects which could be partially reversed by the addition of exogenous
      fibronectin. CONCLUSIONS: These data support the hypothesis that mammary stroma
      responds to tamoxifen treatment in concert with the epithelium and remodels to a
      microenvironment inhibitory to tumour cell progression. Reduced fibronectin
      levels and reduced ECM turnover appear to be hallmarks of the quiescent mammary
      microenvironment. These data may provide insight into attributes of a mammary
      microenvironment that facilitate tumour dormancy.

PMID- 19173738
TI  - Determination of patient-specific internal gross tumor volumes for lung cancer
      using four-dimensional computed tomography.
AB  - BACKGROUND: To determine the optimal approach to delineating patient-specific
      internal gross target volumes (IGTV) from four-dimensional (4-D) computed
      tomography (CT) image data sets used in the planning of radiation treatment for
      lung cancers. METHODS: We analyzed 4D-CT image data sets of 27 consecutive
      patients with non-small-cell lung cancer (stage I: 17, stage III: 10). The IGTV,
      defined to be the envelope of respiratory motion of the gross tumor volume in
      each 4D-CT data set was delineated manually using four techniques: (1) combining
      the gross tumor volume (GTV) contours from ten respiratory phases
      (IGTVAllPhases); (2) combining the GTV contours from two extreme respiratory
      phases (0% and 50%) (IGTV2Phases); (3) defining the GTV contour using the maximum
      intensity projection (MIP) (IGTVMIP); and (4) defining the GTV contour using the
      MIP with modification based on visual verification of contours in individual
      respiratory phase (IGTVMIP-Modified). Using the IGTVAllPhases as the optimum
      IGTV, we compared volumes, matching indices, and extent of target missing using
      the IGTVs based on the other three approaches. RESULTS: The IGTVMIP and
      IGTV2Phases were significantly smaller than the IGTVAllPhases (p < 0.006 for
      stage I and p < 0.002 for stage III). However, the values of the IGTVMIP-Modified
      were close to those determined from IGTVAllPhases (p = 0.08). IGTVMIP-Modified
      also matched the best with IGTVAllPhases. CONCLUSION: IGTVMIP and IGTV2Phases
      underestimate IGTVs. IGTVMIP-Modified is recommended to improve IGTV delineation
      in lung cancer.

PMID- 19173737
TI  - Metastatic renal cell cancer treatments: an indirect comparison meta-analysis.
AB  - BACKGROUND: Treatment for metastatic renal cell cancer (mRCC) has advanced
      dramatically with understanding of the pathogenesis of the disease. New treatment
      options may provide improved progression-free survival (PFS). We aimed to
      determine the relative effectiveness of new therapies in this field. METHODS: We
      conducted comprehensive searches of 11 electronic databases from inception to
      April 2008. We included randomized trials (RCTs) that evaluated bevacizumab,
      sorafenib, and sunitinib. Two reviewers independently extracted data, in
      duplicate. Our primary outcome was investigator-assessed PFS. We performed random
      effects meta-analysis with a mixed treatment comparison analysis. RESULTS: We
      included 3 bevacizumab (2 of bevacizumab plus interferon-a [IFN-a]), 2 sorafenib,
      1 sunitinib, and 1 temsirolimus trials (total n = 3,957). All interventions offer
      advantages for PFS. Using indirect comparisons with interferon-alpha as the
      common comparator, we found that sunitinib was superior to both sorafenib (HR
      0.58, 95% CI, 0.38-0.86, P = < 0.001) and bevacizumab + IFN-a (HR 0.75, 95% CI,
      0.60-0.93, P = 0.001). Sorafenib was not statistically different from bevacizumab
      +IFN-a in this same indirect comparison analysis (HR 0.77, 95% CI, 0.52-1.13, P =
      0.23). Using placebo as the similar comparator, we were unable to display a
      significant difference between sorafenib and bevacizumab alone (HR 0.81, 95% CI,
      0.58-1.12, P = 0.23). Temsirolimus provided significant PFS in patients with poor
      prognosis (HR 0.69, 95% CI, 0.57-0.85). CONCLUSION: New interventions for mRCC
      offer a favourable PFS for mRCC compared to interferon-alpha and placebo.

PMID- 19173739
TI  - Guideline adherence and patient satisfaction in the treatment of inflammatory
      bowel disorders--an evaluation study.
AB  - BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are the most
      frequent inflammatory bowel disorders (IBD). IBD cause a significant burden to
      society due to extensive health care utilization from the first clinical symptoms
      until diagnosis and thereafter due to direct and indirect costs. Besides the
      socio-economic impact of CD and UC, gastrointestinal and extraintestinal symptoms
      affect quality of life, but there is remarkably little data about the quality of
      treatment as assessed by patient satisfaction, quality of life and adherence to
      guidelines. Thus the aim of this study was to identify variables that influence
      quality of treatment and quality of life as well as patient satisfaction.
      METHODS: The Essener Zirkel Study was a cross sectional study of 86 IBD-patients
      with a confirmed diagnosis of CD or UC. They were recruited at primary, secondary
      and tertiary care settings. Quality of treatment, quality of life and patient
      satisfaction were evaluated. Consulting behaviour and number of examinations,
      duration of disease and variables regarding adherence to guidelines were
      evaluated, too. RESULTS: 59 (69%) patients had CD and 27 had UC (31%). 19% spent
      more than four years until the suspected diagnosis of IBD was confirmed and
      visited more than five physicians. All patients showed a significantly reduced
      quality of life compared to the 1998 German normative population. In spite of
      being under medical treatment, nearly half of the patients suffered from strong
      quality of life restricting symptoms. Over all, 35% described their treatment as
      moderate or bad. Patients who consulted psychotherapists and non-medical
      practitioners suffered significantly less from depression. CONCLUSION: Besides
      structural deficiencies due to the health care policy, we revealed the adherence
      to guidelines to be a problem area. Our findings support the assumption, that
      providing better health care and especially maintaining constant patient
      physician communication improves patient satisfaction.

PMID- 19173740
TI  - Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung
      inflammation in mice.
AB  - BACKGROUND: Inflammation may contribute to the pathogenesis of various forms of
      pulmonary hypertension (PH). Recent studies in patients with idiopathic PH or PH
      associated with underlying diseases suggest a role for interleukin-6 (IL-6).
      METHODS: To determine whether endogenous IL-6 contributes to mediate hypoxic PH
      and lung inflammation, we studied IL-6-deficient (IL-6-/-) and wild-type (IL
      6+/+) mice exposed to hypoxia for 2 weeks. RESULTS: Right ventricular systolic
      pressure, right ventricle hypertrophy, and the number and media thickness of
      muscular pulmonary vessels were decreased in IL-6-/- mice compared to wild-type
      controls after 2 weeks' hypoxia, although the pressure response to acute hypoxia
      was similar in IL-6+/+ and IL-6-/- mice. Hypoxia exposure of IL-6+/+ mice led to
      marked increases in IL-6 mRNA and protein levels within the first week, with
      positive IL-6 immunostaining in the pulmonary vessel walls. Lung IL-6 receptor
      and gp 130 (the IL-6 signal transducer) mRNA levels increased after 1 and 2
      weeks' hypoxia. In vitro studies of cultured human pulmonary-artery smooth-muscle
      cells (PA-SMCs) and microvascular endothelial cells revealed prominent synthesis
      of IL-6 by PA-SMCs, with further stimulation by hypoxia. IL-6 also markedly
      stimulated PA-SMC migration without affecting proliferation. Hypoxic IL-6-/- mice
      showed less inflammatory cell recruitment in the lungs, compared to hypoxic wild
      type mice, as assessed by lung protein levels and immunostaining for the specific
      macrophage marker F4/80, with no difference in lung expression of adhesion
      molecules or cytokines. CONCLUSION: These data suggest that IL-6 may be actively
      involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling
      in mice.

PMID- 19173741
TI  - Eumalacostracan phylogeny and total evidence: limitations of the usual suspects.
AB  - BACKGROUND: The phylogeny of Eumalacostraca (Crustacea) remains elusive, despite
      over a century of interest. Recent morphological and molecular phylogenies appear
      highly incongruent, but this has not been assessed quantitatively. Moreover, 18S
      rRNA trees show striking branch length differences between species, accompanied
      by a conspicuous clustering of taxa with similar branch lengths. Surprisingly,
      previous research found no rate heterogeneity. Hitherto, no phylogenetic analysis
      of all major eumalacostracan taxa (orders) has either combined evidence from
      multiple loci, or combined molecular and morphological evidence. RESULTS: We
      combined evidence from four nuclear ribosomal and mitochondrial loci (18S rRNA,
      28S rRNA, 16S rRNA, and cytochrome c oxidase subunit I) with a newly synthesized
      morphological dataset. We tested the homogeneity of data partitions, both in
      terms of character congruence and the topological congruence of inferred trees.
      We also performed Bayesian and parsimony analyses on separate and combined
      partitions, and tested the contribution of each partition. We tested for
      potential long-branch attraction (LBA) using taxon deletion experiments, and with
      relative rate tests. Additionally we searched for molecular polytomies (spurious
      clades). Lastly, we investigated the phylogenetic stability of taxa, and assessed
      their impact on inferred relationships over the whole tree. We detected
      significant conflict between data partitions, especially between morphology and
      molecules. We found significant rate heterogeneity between species for both the
      18S rRNA and combined datasets, introducing the possibility of LBA. As a test
      case, we showed that LBA probably affected the position of Spelaeogriphacea in
      the combined molecular evidence analysis. We also demonstrated that several
      clades, including the previously reported and surprising clade of Amphipoda plus
      Spelaeogriphacea, are 'supported' by zero length branches. Furthermore we showed
      that different sets of taxa have the greatest impact upon the relationships
      within molecular versus morphological trees. CONCLUSION: Rate heterogeneity and
      conflict between data partitions mean that existing molecular and morphological
      evidence is unable to resolve a well-supported eumalacostracan phylogeny. We
      believe that it will be necessary to look beyond the most commonly utilized
      sources of data (nuclear ribosomal and mitochondrial sequences) to obtain a
      robust tree in the future.

PMID- 19173742
TI  - Zyxin is a novel interacting partner for SIRT1.
AB  - BACKGROUND: SIRT1 is a mammalian homologue of NAD+-dependent deacetylase sirtuin
      family. It regulates longevity in several model organisms and is involved with
      cell survival, differentiation, metabolism among other processes in mammalian
      cells. SIRT1 modulates functions of various key targets via deacetylation. Recent
      studies have revealed SIRT1 protects neurons from axonal degeneration or
      neurodegeneration. Further, SIRT1 null mice exhibit growth retardation and
      developmental defects, suggesting its critical roles in neurons and development.
      RESULTS: To identify novel binding partners for SIRT1 in the central nervous
      system, we performed yeast two-hybrid screening on human fetal brain cDNA library
      and found that zyxin is a possible binding partner. SIRT1 and zyxin transcript
      were both preferentially expressed in developmental mouse brain. Zyxin
      accumulates in the nucleus where it is co-localized with SIRT1 after treatment
      with leptomycin B in COS-7 cells. Furthermore, SIRT1 deacetylates zyxin,
      suggesting SIRT1 could interact with nuclear-accumulated zyxin and modulate its
      function through deacetylation. CONCLUSION: Zyxin could be a novel interacting
      partner of SIRT1. Zyxin is an adaptor protein at focal adhesion plaque,
      regulating cytoskeletal dynamics and signal transduction to convey signal from
      the ECM (extracellular matrix) to the nucleus. Our results raise the possibility
      that SIRT1 regulates signal transmission from ECM to the nucleus by modulating
      the functions of zyxin via deacetylation.

PMID- 19173743
TI  - A randomised controlled trial of the Neuro Emotional Technique (NET) for
      childhood Attention Deficit Hyperactivity Disorder (ADHD): a protocol.
AB  - BACKGROUND: An abundance of literature is dedicated to research for the treatment
      of Attention Deficit Hyperactivity Disorder (ADHD). Most, is in the area of
      pharmacological therapies with less emphasis in psychotherapy and psychosocial
      interventions and even less in the area of complementary and alternative medicine
      (CAM).The use of CAM has increased over the years, especially for developmental
      and behavioral disorders, such as ADHD. 60-65% of parents with children with ADHD
      have used CAM. Medical evidence supports a multidisciplinary approach (i.e.
      pharmacological and psychosocial) for the best clinical outcomes. The Neuro
      Emotional Technique (NET), a branch of Chiropractic, was designed to address the
      biopsychosocial aspects of acute and chronic conditions including non
      musculoskeletal conditions. Anecdotally, it has been suggested that ADHD may be
      managed effectively by NET. DESIGN/METHODS: A placebo controlled, double blind
      randomised clinical trial was designed to assess the effectiveness of NET on a
      cohort of children with medically diagnosed ADHD. Children aged 5-12 years who
      met the inclusion criteria were randomised to one of three groups. The control
      group continued on their existing medical regimen and the intervention and
      placebo groups had the addition of the NET and sham NET protocols added to their
      regimen respectively. These two groups attended a clinical facility twice a week
      for the first month and then once a month for six months. The Conners' Parent and
      Teacher Rating Scales (CRS) were used at the start of the study to establish
      baseline data and then in one month and in seven months time, at the conclusion
      of the study. The primary outcome measures chosen were the Conners' ADHD Index
      and Conners' Global Index. The secondary outcome measures chosen were the DSM-IV:
      Inattentive, the DSM-IV:Hyperactive-Impulsive, and the DSM-IV:Total subscales
      from the Conners' Rating Scales, monitoring changes in inattention, hyperactivity
      and impulsivity. Calculations for the sample size were set with a significance
      level of 0.05 and the power of 80%, yielding a sample size of 93. DISCUSSION: The
      present study should provide information as to whether the addition of NET to an
      existing medical regimen can improve outcomes for children with ADHD. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trial Registration Number: ANZCTRN
      012606000332527.

PMID- 19173744
TI  - The Genome Reverse Compiler: an explorative annotation tool.
AB  - BACKGROUND: As sequencing costs have decreased, whole genome sequencing has
      become a viable and integral part of biological laboratory research. However, the
      tools with which genes can be found and functionally characterized have not been
      readily adapted to be part of the everyday biological sciences toolkit. Most
      annotation pipelines remain as a service provided by large institutions or come
      as an unwieldy conglomerate of independent components, each requiring their own
      setup and maintenance. RESULTS: To address this issue we have created the Genome
      Reverse Compiler, an easy-to-use, open-source, automated annotation tool. The GRC
      is independent of third party software installs and only requires a Linux
      operating system. This stands in contrast to most annotation packages, which
      typically require installation of relational databases, sequence similarity
      software, and a number of other programming language modules. We provide details
      on the methodology used by GRC and evaluate its performance on several groups of
      prokaryotes using GRC's built in comparison module. CONCLUSION: Traditionally, to
      perform whole genome annotation a user would either set up a pipeline or take
      advantage of an online service. With GRC the user need only provide the genome he
      or she wants to annotate and the function resource files to use. The result is
      high usability and a very minimal learning curve for the intended audience of
      life science researchers and bioinformaticians. We believe that the GRC fills a
      valuable niche in allowing users to perform explorative, whole-genome annotation.

PMID- 19173745
TI  - Independent component analysis of Alzheimer's DNA microarray gene expression
      data.
AB  - BACKGROUND: Gene microarray technology is an effective tool to investigate the
      simultaneous activity of multiple cellular pathways from hundreds to thousands of
      genes. However, because data in the colossal amounts generated by DNA microarray
      technology are usually complex, noisy, high-dimensional, and often hindered by
      low statistical power, their exploitation is difficult. To overcome these
      problems, two kinds of unsupervised analysis methods for microarray data:
      principal component analysis (PCA) and independent component analysis (ICA) have
      been developed to accomplish the task. PCA projects the data into a new space
      spanned by the principal components that are mutually orthonormal to each other.
      The constraint of mutual orthogonality and second-order statistics technique
      within PCA algorithms, however, may not be applied to the biological systems
      studied. Extracting and characterizing the most informative features of the
      biological signals, however, require higher-order statistics. RESULTS: ICA is one
      of the unsupervised algorithms that can extract higher-order statistical
      structures from data and has been applied to DNA microarray gene expression data
      analysis. We performed FastICA method on DNA microarray gene expression data from
      Alzheimer's disease (AD) hippocampal tissue samples and consequential gene
      clustering. Experimental results showed that the ICA method can improve the
      clustering results of AD samples and identify significant genes. More than 50
      significant genes with high expression levels in severe AD were extracted,
      representing immunity-related protein, metal-related protein, membrane protein,
      lipoprotein, neuropeptide, cytoskeleton protein, cellular binding protein, and
      ribosomal protein. Within the aforementioned categories, our method also found 37
      significant genes with low expression levels. Moreover, it is worth noting that
      some oncogenes and phosphorylation-related proteins are expressed in low levels.
      In comparison to the PCA and support vector machine recursive feature elimination
      (SVM-RFE) methods, which are widely used in microarray data analysis, ICA can
      identify more AD-related genes. Furthermore, we have validated and identified
      many genes that are associated with AD pathogenesis. CONCLUSION: We demonstrated
      that ICA exploits higher-order statistics to identify gene expression profiles as
      linear combinations of elementary expression patterns that lead to the
      construction of potential AD-related pathogenic pathways. Our computing results
      also validated that the ICA model outperformed PCA and the SVM-RFE method. This
      report shows that ICA as a microarray data analysis tool can help us to elucidate
      the molecular taxonomy of AD and other multifactorial and polygenic complex
      diseases.

PMID- 19173746
TI  - The retinoic acid binding protein CRABP2 is increased in murine models of
      degenerative joint disease.
AB  - INTRODUCTION: Osteoarthritis (OA) is a debilitating disease with poorly defined
      aetiology. Multiple signals are involved in directing the formation of cartilage
      during development and the vitamin A derivatives, the retinoids, figure
      prominently in embryonic cartilage formation. In the present study, we examined
      the expression of a retinoid-regulated gene in murine models of OA. METHODS: Mild
      and moderate forms of an OA-like degenerative disease were created in the mouse
      stifle joint by meniscotibial transection (MTX) and partial meniscectomy (PMX),
      respectively. Joint histopathology was scored using an Osteoarthritis Research
      Society International (OARSI) system and gene expression (Col1a1, Col10a1, Sox9
      and Crabp2) in individual joints was determined using TaqMan quantitative PCR on
      RNA from microdissected articular knee cartilage. RESULTS: For MTX, there was a
      significant increase in the joint score at 10 weeks (n = 4, p < 0.001) in
      comparison to sham surgeries. PMX surgery was slightly more severe and produced
      significant changes in joint score at six (n = 4, p < 0.01), eight (n = 4, p <
      0.001) and 10 (n = 4, p < 0.001) weeks. The expression of Col1a1 was increased in
      both surgical models at two, four and six weeks post-surgery. In contrast,
      Col10a1 and Sox9 for the most part showed no significant difference in expression
      from two to six weeks post-surgery. Crabp2 expression is induced upon activation
      of the retinoid signalling pathway. At two weeks after surgery in the MTX and PMX
      animals, Crabp2 expression was increased about 18-fold and about 10-fold over the
      sham control, respectively. By 10 weeks, Crabp2 expression was increased about
      three-fold (n = 7, not significant) in the MTX animals and about five-fold (n =
      7, p < 0.05) in the PMX animals in comparison to the contralateral control joint.
      CONCLUSIONS: Together, these findings suggest that the retinoid signalling
      pathway is activated early in the osteoarthritic process and is sustained during
      the course of the disease.

PMID- 19173747
TI  - Effects of preferred-exercise prescription compared to usual exercise
      prescription on outcomes for people with non-specific low back pain: a randomized
      controlled trial [ACTRN12608000524392].
AB  - BACKGROUND: Non-specific chronic low back pain (NSCLBP) has become a significant
      problem due to high healthcare utilization, rising costs of care and perceived
      limitations of effectiveness of many current treatments. Systematic reviews have
      repeatedly concluded that, on average across participants, exercise for NSCLBP
      appears effective in decreasing pain and improving function. Not all people with
      NSCLBP benefit from exercise programs and it would assist care-providers and care
      seekers if factors that impact on program effectiveness and success were
      identified. METHODS AND DESIGN: The study will be a randomised controlled trial
      comparing an exercise rehabilitation program informed by a participant
      preferences questionnaire compared to a program without this guideline for
      patients with chronic low back pain. A sample of 150 patients will be recruited
      in Melbourne, Australia through community-based healthcare clinics that provide
      supervised exercise rehabilitation programs for people with non-specific chronic
      low back pain. Clinicians will be randomly assigned to exercise preferences
      questionnaire or no questionnaire and participants will be allocated in a
      concealed manner. A qualitative focus group study of exercise instructor feedback
      about the exercise preferences instrument will be embedded in the research
      design. Two qualitative focus group studies will also be conducted for
      participants in the intervention and the control groups to obtain feedback about
      participants' experiences of the two types of exercise programs. The primary
      outcomes will be functional ability, pain, fear avoidance, exercise adherence.
      DISCUSSION: This trial will evaluate the effectiveness of individualised exercise
      prescription compared to usual exercise prescription for NSCLP and, using
      feedback following the trial, refine the exercise preferences questionnaire.

PMID- 19173748
TI  - Prediction of protein-protein interaction types using association rule based
      classification.
AB  - BACKGROUND: Protein-protein interactions (PPI) can be classified according to
      their characteristics into, for example obligate or transient interactions. The
      identification and characterization of these PPI types may help in the functional
      annotation of new protein complexes and in the prediction of protein interaction
      partners by knowledge driven approaches. RESULTS: This work addresses pattern
      discovery of the interaction sites for four different interaction types to
      characterize and uses them for the prediction of PPI types employing Association
      Rule Based Classification (ARBC) which includes association rule generation and
      posterior classification. We incorporated domain information from protein
      complexes in SCOP proteins and identified 354 domain-interaction sites. 14
      interface properties were calculated from amino acid and secondary structure
      composition and then used to generate a set of association rules characterizing
      these domain-interaction sites employing the APRIORI algorithm. Our results
      regarding the classification of PPI types based on a set of discovered
      association rules shows that the discriminative ability of association rules can
      significantly impact on the prediction power of classification models. We also
      showed that the accuracy of the classification can be improved through the use of
      structural domain information and also the use of secondary structure content.
      CONCLUSION: The advantage of our approach is that we can extract biologically
      significant information from the interpretation of the discovered association
      rules in terms of understandability and interpretability of rules. A web
      application based on our method can be found at
      http://bioinfo.ssu.ac.kr/~shpark/picasso/

PMID- 19173749
TI  - Long-term effects of peroxisome proliferator-activated receptor ligand
      bezafibrate on N-terminal pro-B type natriuretic peptide in patients with
      advanced functional capacity impairment.
AB  - BACKGROUND: The effects of pan-peroxisome proliferator-activated receptor (PPAR)
      ligand bezafibrate on N-terminal pro-B type natriuretic peptide (ProBNP) level in
      patients with coronary artery disease (CAD) is unknown. The current study aimed
      to investigate the long-term effects of bezafibrate on ProBNP level in patients
      with pre-existing CAD and advanced functional capacity impairment. METHODS:
      Metabolic and inflammatory parameters were analyzed from stored frozen serum
      samples obtained from 108 patients enrolled in the Bezafibrate Infarction
      Prevention (BIP) Study. They presented with New York Heart Association (NYHA)
      functional class III, comprising 58 patients in the bezafibrate group and 50 in
      the placebo groups, and completed a 2-year prospective, double-blind, placebo
      controlled follow-up. RESULTS: During follow-up ProBNP level did not change
      significantly in the placebo group, whereas it increased slightly in the
      bezafibrate group, which was older and with lower baseline ProBNP values. No
      significant differences between the groups were found for ProBNP levels after 2
      year of follow-up. Analysis-of-covariance (ANCOVA) -taking into account age and
      baseline ProBNP level- showed that bezafibrate was not associated with
      longitudinal ProBNP changes during the follow-up period (p = 0.3). CONCLUSION:
      Long-term treatment by bezafibrate was not associated with longitudinal ProBNP
      changes in patients with pre-existing CAD and advanced functional capacity
      impairment.

PMID- 19173750
TI  - Bilateral femoral neck fractures in an adult male following minimal trauma after
      a simple mechanical fall: a case report.
AB  - BACKGROUND: Despite being rare there are several reports in the medical
      literature of bilateral femoral neck fractures in adult patients. They have been
      reported to have occurred following major trauma, or as a result of primary or
      secondary bone disease. In this case report we describe for the first time in the
      literature bilateral femoral neck fractures in a patient following minimal trauma
      after a simple mechanical fall. CASE PRESENTATION: We describe the case of an 84
      year-old gentleman who sustained bilateral intracapsular fractures following a
      simple mechanical fall. Prompt diagnosis and early surgical intervention resulted
      in a satisfactory outcome. CONCLUSION: This case highlights that in the elderly,
      even in the absence of primary and secondary bone disease, bilateral neck of
      femur fractures can occur following relatively minor trauma. Consequently, the
      orthopaedic surgeon, emergency physician and general practitioner should be aware
      of this injury, particularly when managing traumatic injuries in confused
      patients.

PMID- 19173751
TI  - Noninvasive ventilation in patients with acute cardiogenic pulmonary edema.
AB  - Acute cardiogenic pulmonary edema (ACPE) is a common cause of respiratory failure
      that necessitates endotracheal intubation. In some patients intubation and its
      attendant complications can be avoided with noninvasive ventilation (NIV). Both
      continuous positive airway pressure (CPAP) and NIV have been evaluated in
      patients with ACPE. Compared to conventional treatment, both CPAP and NIV improve
      vital signs and physiologic variables, and reduce intubation rate, in patients
      with ACPE. Both CPAP and NIV appear to be well tolerated and are not associated
      with any serious adverse events. Initial concern that NIV may be associated with
      a greater risk of myocardial infarction than CPAP was laid to rest by later
      studies. Despite a physiologic rationale that NIV should offer greater benefit
      than CPAP, NIV has not been found to offer any advantages regarding intubation
      rate or mortality compared with CPAP. We review the randomized controlled trials
      and summarize the evidence on NIV and CPAP in patients with ACPE.

PMID- 19173752
TI  - Noninvasive ventilation to shorten the duration of mechanical ventilation.
AB  - Noninvasive ventilation (NIV) successfully treats primary respiratory failure in
      chronic obstructive pulmonary disease (COPD), acute pulmonary edema, and, in some
      patients, hypoxemic respiratory failure. Increasingly clinicians have applied NIV
      in an effort to shorten the duration of mechanical ventilation by facilitating
      weaning and preventing or treating post-extubation respiratory failure.
      Randomized controlled trials (RCTs) indicate that NIV may be an effective weaning
      tool in a subset of patients with acute-on-chronic respiratory failure from COPD,
      and that applying immediate NIV to extubated patients at high risk for extubation
      failure improves outcome by decreasing the need for reintubation. In contrast,
      there is mixed evidence about the effectiveness of NIV to treat established post
      extubation respiratory failure. NIV appeared to be ineffective in heterogeneous
      patient populations in some randomized trials that enrolled relatively few
      patients with COPD, and a case-control study found that NIV decreased the need
      for reintubation in this group. Therefore, as with primary therapy, NIV should be
      considered for patients with COPD and post-extubation respiratory distress.

PMID- 19173753
TI  - Novel uses of noninvasive ventilation.
AB  - Noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) have
      been used in various unusual settings to assist breathing. NIV is now frequently
      used to treat exacerbations of chronic obstructive pulmonary disease and chronic
      respiratory failure in neuromuscular disease. This paper discusses CPAP and NIV
      for postoperative hypoxemia, preventing intubation in high-risk bronchoscopy,
      respiratory failure in pandemics, obesity hypoventilation syndrome, and
      respiratory support during percutaneous endoscopic gastrostomy tube placement.

PMID- 19173754
TI  - Should noninvasive ventilation be used with the do-not-intubate patient?
AB  - Most of the large quantity of data on noninvasive ventilation (NIV) in acute
      respiratory failure is from patients who want all possible treatments and life
      support. Few data are available on NIV in patients who have elected specific
      limits on life support and treatments (eg, patients with do-not-intubate [DNI]
      orders) and patients who are near the end of life and will receive comfort
      measures only (CMO). The most critical issue regarding NIV in DNI and CMO
      patients is informed consent. The patient must be informed of the risks and
      potential benefits of NIV, and must consent to NIV. We have few data on patients'
      attitudes about NIV at end of life. Data from cancer patients at end of life
      suggest that they want to maintain control over care decisions and may want
      treatment that delays death long enough that they can put their affairs in order.
      If informed consent and control of care decisions are assured, then NIV can be
      appropriate in DNI and CMO patients to reverse an acute respiratory failure that
      is not necessarily life-terminating, or to improve patient comfort, or to delay
      death.

PMID- 19173755
TI  - How to initiate a noninvasive ventilation program: bringing the evidence to the
      bedside.
AB  - Noninvasive ventilation (NIV) is under-utilized, despite robust evidence
      supporting its use in appropriately selected patients with acute respiratory
      failure. Diffusion of NIV into practice requires that clinicians view it as
      better than invasive ventilation, that it is perceived as compatible with
      existing approaches to mechanical ventilation, that it is not too difficult to
      apply, that it is trialable, and that its results are visible. Barriers to NIV
      use include lack of awareness of the evidence, lack of agreement with the
      evidence, lack of self-efficacy, unrealistic outcome expectations, and the
      inertia of previous practice. A flexible, tireless, enthusiastic, and
      knowledgeable clinical champion is important when initiating an NIV program.
      Knowledge and training are also important; ideally the training should be one-on
      one and hands-on to the extent possible. Adequate personnel and equipment
      resources are necessary when implementing the program. Guidelines and protocols
      may be useful as educational resources, to avoid clinical conflict and
      consolidate authority. When initiating an NIV program it is important to
      recognize that NIV does not avoid intubation in all cases. Success often improves
      with experience. The available evidence suggests that NIV is cost-effective. For
      optimum success the multidisciplinary nature of NIV application must be
      recognized. The NIV program should be a quality-improvement initiative. Following
      these principles, a successful program can be initiated in any acute-care
      setting.

PMID- 19173756
TI  - Complications of noninvasive ventilation in acute care.
AB  - The use of noninvasive ventilation (NIV) for acute respiratory failure has become
      widespread, but with the newfound beneficial treatments come complications. There
      is credible although somewhat disparate evidence to support the concept that,
      compared to invasive ventilation, NIV can reduce the incidence of infectious
      complications. In selected populations, nosocomial pneumonia appears to be
      significantly less common with NIV than with endotracheal intubation. NIV
      complications range from minor (eg, mask-related difficulties) to serious (eg,
      aspiration and hemodynamic effects). Evidence shows that if NIV is
      inappropriately applied for too long, the consequences may lead to death,
      presumably due to excessive delay of intubation. Despite apparently similar costs
      of treatment for patients with equivalent severity of illness, there is
      substantially less reimbursement for NIV than for intubation. The use of sedation
      in NIV patients has not been systematically studied, and sedation is generally
      underutilized, to avoid complications. Do-not-intubate patients pose a special
      ethical dilemma with regard to NIV, because NIV may conflict with a preexisting
      directive not to use life-support measures in the terminally ill patient.

PMID- 19173757
TI  - Noninvasive ventilation in acute care: controversies and emerging concepts.
AB  - This conference brought together experts on noninvasive ventilation (NIV) to
      discuss and debate the advances in evidence and technology over the past decade.
      A major impetus for the conference was that many institutions have not
      systematically integrated NIV into their clinical practice, despite mounting,
      high-level evidence supporting its effectiveness. NIV clearly improves outcomes
      for patients with chronic obstructive pulmonary disease and acute cardiogenic
      pulmonary edema when instituted as a first-line therapy. Although the evidence is
      less persuasive, initial intervention with NIV also might benefit a carefully
      selected subset of patients with acute lung injury, as well as those with acute
      respiratory failure who are immunocompromised. The papers in this and last
      month's special issue of the Journal provide an informative guide for clinicians
      attempting to implement NIV in their institutions. This paper summarizes the
      major findings from each presentation and the discussions that followed.

PMID- 19173759
TI  - Introduction: are dementia with Lewy bodies and Parkinson's disease dementia the
      same condition?

PMID- 19173760
TI  - Places, social relations and activities in the everyday lives of older adults
      with psychiatric disabilities: an interview study.
AB  - BACKGROUND: Knowledge about the daily life of older adults with psychiatric
      disabilities is extremely limited, especially from the standpoint of the
      individual. The overall aim of this study was to describe and analyze the ways in
      which older adults with a psychiatric disability experience places, social
      relations and activities in different arenas of their everyday lives. METHOD:
      Twelve older adults (>55 years) with a psychiatric disability were interviewed
      either once or twice, using different interview techniques. The first interviews
      were semi-structured and the second were in-depth interviews guided by a site
      map. The interview texts were analyzed using qualitative content analysis,
      proceeding from open to focused coding in several steps. RESULTS: Although the
      respondents spent most of their time in their own homes, some also spent a lot of
      time at day-care centers and other similar places. The amount of time spent in
      places in the public arena varied a great deal. The interviewees' experiences of
      the places, relationships and activities in their everyday lives can be related
      to aspects of freedom and coercion, internal and external structure, and
      relationships and support. CONCLUSION: The provision of a varied range of
      services and support in diverse settings in order to make these accessible to
      persons of different ages and needs is an important challenge for welfare
      politics.

PMID- 19173761
TI  - Dementia with Lewy bodies and Parkinson's disease dementia may best be viewed as
      two distinct entities.

PMID- 19173758
TI  - Membrane transporters and folate homeostasis: intestinal absorption and transport
      into systemic compartments and tissues.
AB  - Members of the family of B9 vitamins are commonly known as folates. They are
      derived entirely from dietary sources and are key one-carbon donors required for
      de novo nucleotide and methionine synthesis. These highly hydrophilic molecules
      use several genetically distinct and functionally diverse transport systems to
      enter cells: the reduced folate carrier, the proton-coupled folate transporter
      and the folate receptors. Each plays a unique role in mediating folate transport
      across epithelia and into systemic tissues. The mechanism of intestinal folate
      absorption was recently uncovered, revealing the genetic basis for the autosomal
      recessive disorder hereditary folate malabsorption, which results from loss-of
      function mutations in the proton-coupled folate transporter gene. It is therefore
      now possible to piece together how these folate transporters contribute, both
      individually and collectively, to folate homeostasis in humans. This review
      focuses on the physiological roles of the major folate transporters, with a brief
      consideration of their impact on the pharmacological activities of antifolates.

PMID- 19173762
TI  - Parkinson's disease dementia and dementia with Lewy bodies: different aspects of
      one entity.

PMID- 19173763
TI  - Commentary: DLB and PDD: the same or different? Is there a debate?

PMID- 19173764
TI  - Prevalence of Dirofilaria immitis in dogs from Hatay province, Turkey.
AB  - The present study was conducted to determine the prevalence of canine
      dirofilariosis in Hatay province, south of Turkey. A total of 269 blood samples
      were collected from owned dogs in this multi-centre survey between March and July
      2006. Blood samples were examined by modified Knott and enzyme-linked
      immunosorbent assay (ELISA) techniques to detect circulating microfilariae and
      antigens of Dirofilaria immitis, respectively. Seventy out of 269 dogs (26.0%)
      were positive for D. immitis. However, 61.4% of positive dogs had occult
      infection. The prevalence of canine dirofilariosis was heterogeneous in Hatay
      province, with higher values in shoreline (33.0%) and riverside (30.9%) areas
      followed by the lowland (25.5%) or mountainous (15.2%) areas. No statistically
      significant differences were observed in relation to sex (females, 33.3%; males,
      24.4%, P>0.05). When evaluating the prevalence of D. immitis by age, the highest
      prevalence was observed in dogs older than 4 years of age. Large breeds (29.6%)
      and the dogs living outdoors (30.2%) showed a higher prevalence in comparison to
      small breeds (21.4%) and the dogs living indoors (10.5%), respectively. In
      conclusion, according to the results of this study canine dirofilariosis had a
      high prevalence in Hatay province. Therefore, prophylaxis against heartworm is
      advisable to decrease the incidence of canine dirofilariosis.

PMID- 19173765
TI  - Longitudinal decrements in iron status during military training in female
      soldiers.
AB  - Fe is an essential micronutrient required for optimal cognitive and physical
      performance. Cross-sectional studies indicate that training degrades Fe status in
      female military personnel; however, longitudinal studies to measure the direct
      impact of military training on Fe status and performance have not been conducted.
      As such, the objective of the present study was to determine the longitudinal
      effects of military training on Fe status in female soldiers. Fe status was
      assessed in ninety-four female soldiers immediately before and following a 9-week
      basic combat training (BCT) course. Fe status indicators included Hb, erythrocyte
      distribution width (RDW), serum ferritin, transferrin saturation and soluble
      transferrin receptor (sTfR). A 2-mile (3.2 km) run test was performed at the end
      of BCT to assess aerobic performance. Fe status was affected by BCT, as all Fe
      status indicators, excluding Hb, were diminished (P < or = 0.01) at the end of
      BCT. Fe status indicators at the end of BCT (Hb and RDW) were associated (P < or
      = 0.05) with running performance, as was the change in sTfR over the training
      period (r 0.320; P < or = 0.05). In conclusion, Fe status in female soldiers is
      degraded during BCT, and degraded Fe status is associated with diminished aerobic
      performance. Female athletes and military personnel should strive to maintain Fe
      status to optimise physical performance.

PMID- 19173766
TI  - The distribution and accumulation of fucoxanthin and its metabolites after oral
      administration in mice.
AB  - The pharmacokinetics of dietary fucoxanthin, one of the xanthophylls in brown sea
      algae, is little understood. In the present study, mice were orally administered
      fucoxanthin, and the distribution and accumulation of fucoxanthin and its
      metabolites fucoxanthinol and amarouciaxanthin A were measured in the plasma,
      erythrocytes, liver, lung, kidney, heart, spleen and adipose tissue. In a single
      oral administration of 160 nmol fucoxanthin, fucoxanthinol and amarouciaxanthin A
      were detectable in all specimens tested in the present study, but fucoxanthin was
      not. The time at maximum concentration (Tmax) of these metabolites in adipose
      tissue was 24 h, while the Tmax in the others was 4 h. The area under the curve
      to infinity (AUCinfinity) of fucoxanthinol in the liver was the highest value
      (4680 nmol/g x h) among the tissues tested in the present study, while the
      AUCinfinity of amarouciaxanthin A in adipose tissue was the highest value (4630
      nmol/g x h). In daily oral administration of 160 nmol fucoxanthin for 1 week,
      fucoxanthin was also detectable in the tissues even at a low concentration. The
      amount of fucoxanthinol was 123 nmol/g in the heart and 85.2 nmol/g in the liver.
      Amarouciaxanthin A in the adipose tissue was distributed at a concentration of
      97.5 nmol/g. These results demonstrate that dietary fucoxanthin accumulates in
      the heart and liver as fucoxanthinol and in adipose tissue as amarouciaxanthin A.

PMID- 19173767
TI  - Partitioning of nutrient net fluxes across the portal-drained viscera in sheep
      fed twice daily: effect of dietary protein degradability.
AB  - Extrusion is used to decrease leguminous seed protein degradability in the rumen
      in order to shift part of the dietary protein digestion towards the small
      intestine. The effect of such displacement of digestion site on the partitioning
      of nutrient net fluxes across the gastrointestinal tract was studied using four
      sheep fitted with catheters and blood-flow probes, allowing measurements across
      the rumen, the mesenteric-drained viscera (MDV) and the portal-drained viscera
      (PDV). Two diets containing 34 % of pea seeds were tested in a crossover design.
      They differed only according to pea treatment: raw pea (RP) or extruded pea (EP)
      diet. Rumen undegradable protein (RUP) accounted for 23 and 40 % of dietary crude
      protein for RP and EP diets, respectively. Across the rumen wall, ammonia net
      flux was lower with EP diet, whereas urea net flux was not different. Across the
      MDV, free amino acid (FAA) net flux was greater with EP diet, whereas peptide
      amino acid net flux was not different, accounting for 7 % of the non-protein
      amino acid net release. From RP to EP diet, PDV net flux of ammonia decreased by
      23 %, whereas FAA net release increased by 21 %. The difference in dietary RUP
      did not affect the PDV net flux of SCFA, 3-hydroxybutyrate, lactate and glucose.
      In conclusion, the partial shift in pea protein digestion from the rumen to the
      small intestine did not affect the portal net balance of N, but decreased N loss
      from the rumen, and increased amino acid intestinal absorption and portal
      delivery.

PMID- 19173768
TI  - Prenatal arachidonic acid exposure and selected immune-related variables in
      childhood.
AB  - Arachidonic acid (AA) is considered essential in fetal development and some of
      its metabolites are thought to be important mediators of the immune responses.
      Therefore, we studied whether prenatal exposure to AA is associated with some
      immune-related clinical conditions and plasma markers in childhood. In 280
      children aged 7 years, atopy, lung function and plasma inflammation markers were
      measured and their relationships with early AA exposure were studied by linear
      and logistic regression analyses. AA exposure was deduced from AA concentrations
      in plasma phospholipids of the mothers collected at several time points during
      pregnancy and at delivery, and in umbilical cord plasma and arterial and venous
      wall phospholipids. In unadjusted regression analyses, significant positive
      associations were observed between maternal AA concentrations at 16 and 32 weeks
      of pregnancy (proxies for fetal AA exposure) and peak expiratory flow decline
      after maximal physical exercise and plasma fibrinogen concentrations of their
      children, respectively. However, after correction for relevant covariables, only
      trends remained. A significant negative relationship was observed between AA
      concentrations in cord plasma (reflecting prenatal AA exposure) and the average
      daily amplitude of peak expiratory flow at rest, which lost significance after
      appropriate adjustment. Because of these few, weak and inconsistent
      relationships, a major impact of early-life exposure to AA on atopy, lung
      function and selected plasma inflammation markers of children at 7 years of age
      seems unlikely.

PMID- 19173769
TI  - Dietary vitamin E, brain redox status and expression of Alzheimer's disease
      relevant genes in rats.
AB  - Oxidative stress is one of the major pathological features of Alzheimer's disease
      (AD). Here, we investigated whether dietary vitamin E (VE) depletion may induce
      adverse effects and supplementation with alpha-tocopherol (alphaT) may result in
      beneficial effects on redox status and the regulation of genes relevant in the
      pathogenesis of AD in healthy rats. Three groups of eight male rats each were fed
      diets with deficient ( < 1 mg alphaT equivalents/kg diet), marginal (9 mg alphaT
      equivalents/kg diet) or sufficient (18 mg alphaT equivalents/kg diet)
      concentrations of natural-source VE for 6 months; a fourth group was fed the VE
      sufficient diet fortified with alphaT (total VE, 146 mg alphaT equivalents/kg
      diet). Feeding of the experimental diets dose dependently altered alphaT
      concentrations in the cortex and plasma. No significant changes in F2-isoprostane
      concentrations, activities of antioxidative enzymes (total superoxide dismutase,
      Se-dependent glutathione peroxidase) and concentrations of glutathione or the
      expression of AD-relevant genes were observed. In this non-AD model, depletion of
      VE did not induce adverse effects and supplementation of alphaT did not induce
      positive effects on the parameters related to the progression of AD.

PMID- 19173770
TI  - Increasing sodium intake from a previous low or high intake affects water,  
      electrolyte and acid-base balance differently.
AB  - Contrasting data are published on the effects of high salt intake (between 300
      and 660 mmol/d) on Na balance and fluid retention. In some studies high levels of
      NaCl intake (400, 440, 550 and 660 mmol/d) led to positive Na balances without
      fluid retention. To test the relevance of different baseline NaCl intake levels
      on changes in metabolic water, Na, K, chloride and acid-base balance, a 28 d
      clinical trial ('Salty Life 6') was carried out in a metabolic ward. Nine healthy
      male volunteers (aged 25.7 (SD 3.1) years; body mass (BM) 71.4 (SD 4.0) kg)
      participated in the present study. Four consecutive levels of NaCl intake: low (6
      d, 0.7 mmol NaCl/kg BM per d), average normal (6 d, 2.8 mmol NaCl/kg BM per d),
      high (10 d, 7.7 mmol NaCl/kg BM per d), and low again (6 d, 0.7 mmol NaCl/kg BM
      per d) were tested. Urine osmolality, extracellular volume (ECV) and plasma
      volume (PV), cumulative metabolic Na, K, chloride and fluid balances, mRNA
      expression of two glycosaminoglycan (GAG) polymerisation genes, capillary blood
      pH, bicarbonate and base excess were measured. During average normal NaCl intake,
      193 (SEM 19) mmol Na were retained and ECV (+2.02 (SEM 0.31) litres; P<0.001) and
      PV (+0.57 (SEM 0.13) litres; P<0.001) increased. During high NaCl intake, 244
      (SEM 77) mmol Na were retained but ECV did not increase (ECV -0.54 (SEM 0.30)
      litres, P=0.+89; PV +0.27 (SEM 0.25) litres, P=0.283). mRNA expression of GAG
      polymerisation genes increased with rise in NaCl intake, while pH (P<0.01) and
      bicarbonate (P<0.001) levels decreased. We conclude that a high NaCl intake may
      increase GAG synthesis; this might play a role in osmotically inactive Na
      retention in humans.

PMID- 19173772
TI  - Rapid diagnostic tests for the home-based management of malaria, in a high
      transmission area.
AB  - Rapid diagnostic tests (RDT) are sometimes recommended to improve the home-based
      management of malaria. The accuracy of an RDT for the detection of clinical
      malaria and the presence of malarial parasites has recently been evaluated in a
      high-transmission area of southern Mali. During the same study, the cost
      effectiveness of a 'test-and-treat' strategy for the home-based management of
      malaria (based on an artemisinin-combination therapy) was compared with that of a
      'treat-all' strategy. Overall, 301 patients, of all ages, each of whom had been
      considered a presumptive case of uncomplicated malaria by a village healthworker,
      were checked with a commercial RDT (Paracheck-Pf). The sensitivity, specificity,
      and positive and negative predictive values of this test, compared with the
      results of microscopy and two different definitions of clinical malaria, were
      then determined. The RDT was found to be 82.9% sensitive (with a 95% confidence
      interval of 78.0%-87.1%) and 78.9% (63.9%-89.7%) specific compared with the
      detection of parasites by microscopy. In the detection of clinical malaria, it
      was 95.2% (91.3%-97.6%) sensitive and 57.4% (48.2%-66.2%) specific compared with
      a general practitioner's diagnosis of the disease, and 100.0% (94.5%-100.0%)
      sensitive but only 30.2% (24.8%-36.2%) specific when compared against the
      fulfillment of the World Health Organization's (2003) research criteria for
      uncomplicated malaria. Among children aged 0-5 years, the cost of the 'test-and
      treat' strategy, per episode, was about twice that of the 'treat-all' (U.S.$1.0.
      v. U.S.$0.5). In older subjects, however, the two strategies were equally costly
      (approximately U.S.$2/episode). In conclusion, for children aged 0-5 years in a
      high-transmission area of sub-Saharan Africa, use of the RDT was not cost
      effective compared with the presumptive treatment of malaria with an ACT. In
      older patients, use of the RDT did not reduce costs. The question remains whether
      either of the strategies investigated can be made affordable for the affected
      population.

PMID- 19173773
TI  - Impact of the South-to-North Water Diversion Project on the transmission of
      Schistosoma japonicum in China.
AB  - The South-to-North Water Diversion Project (SNWDP) is currently the key,
      national, water-conservation project in China, designed to optimise the use of
      water resources and relieve the water shortages in the north of the country. As
      one of the main water intakes for the project, that of the Eastern Route Scheme
      (ERS), is a breeding site for Oncomelania hupensis (the intermediate host of
      Schistosoma japonicum), there is concern that the snail may be carried far to the
      north, in the water passing through the project. To see if they could survive and
      breed to the north of their current range in China, O. hupensis were collected in
      marshland near Nanjing City and transferred to cages, on the banks of fish ponds,
      in the cities of Zhenjiang (in Jiangsu province, at 32 degrees 10'N), Xuzhou (in
      the same province but at a latitude of 34 degrees 23'N) and Jining (in Shandong
      province, at 35 degrees 23'N). Except over the first 6 months in Xuzhou, the
      snails moved north of their natural distribution did not survive and reproduce as
      well as those in Zhenjiang, and all those transferred to Jining died out within 1
      year. Although the snail populations in Xuzhou survived for 7-8 years and
      retained their infectivity to S. japonicum, histological and histochemical
      studies revealed abnormalities in the reproductive organs of these snails. It is
      concluded that, unless global warming significantly increases the minimum winter
      temperatures in northern China, the SNWDP is unlikely to result in the northward
      spread of schistosomiasis japonica.

PMID- 19173774
TI  - Mansonella perstans: safety and efficacy of ivermectin alone, albendazole alone
      and the two drugs in combination.
AB  - The safety and efficacy of a single dose of ivermectin alone (150-200 microg/kg
      bodyweight), albendazole alone (400 mg) or the combination of these two drugs was
      assessed, in Uganda, in three groups of individuals infected with Mansonella
      perstans (with 15, 13 and 15 subjects in each group, respectively). No side
      effects were observed or reported during the first 7 days post-treatment and
      every subject remained microfilaraemic during the 12 months of follow-up. In the
      subjects given ivermectin alone or albendazole alone, the microfilarial
      intensities consistently remained close to their pre-treatment levels. In the
      subjects given both drugs, however, the microfilarial intensities decreased
      slightly after treatment and at 1 and 3 months post-treatment (but not at 6, 9 or
      12 months) they were significantly lower than in the two other groups combined.
      The three single-dose drug regimens investigated were thus well tolerated but had
      disappointingly low efficacies in the treatment of M. perstans microfilaraemias.

PMID- 19173775
TI  - Antimicrobial resistance and pathogenicity of Escherichia coli isolated from
      common dairy products in the Lebanon.
AB  - In a recent study, bacteria have been isolated from popular Lebanese dairy
      products, which had been collected in the Beqaa Valley, in north-eastern Lebanon.
      The foods investigated were two cheeses (shankleesh and baladi) and a dried
      fermented mixture of yogurt and wheat grains (kishk). Bacterial colonies on
      McConkey and sorbitol-McConkey agar that showed the morphology of Escherichia
      coli were biochemically tested and then classified, using PCR-based assays, into
      the various strains of pathogenic and non-pathogenic E. coli. Some of the
      confirmed E. coli isolates were proven to be pathogenic, including two identified
      as E. coli O157:H7. When the pathogenic isolates were tested for their
      susceptibility to 10 different antibiotics (all commonly used, by clinicians and
      veterinarians, for the treatment of infections with Gram-negative bacteria), each
      tested isolate was found to be highly resistant to at least one antibiotic. It
      therefore appears that, in Lebanon, some popular dairy products pose a public
      health hazard, acting as vehicles for the transmission of drug-resistant
      pathogens.

PMID- 19173776
TI  - Non-oliguric renal failure-a presentation of leptospirosis.
AB  - Within the last 3 years, two children with non-oliguric renal failure following
      leptospirosis have been observed at the B. J. Wadia Hospital for Children, in the
      Indian city of Mumbai. Both cases presented during the monsoon season, with
      fever, abdominal pain and elevated concentrations of serum creatinine (4.3 and
      5.6 mg/dl). Neither case required dialysis and both were successfully treated
      with penicillin. Both recovered completely and gave normal results in their post
      treatment renal-function tests.

PMID- 19173777
TI  - Ecological aspects of the free-living ticks (Acari: Ixodidae) on animal trails
      within Atlantic rainforest in south-eastern Brazil.
AB  - In a recent ecological study of the ticks on animal trails within an area of
      Atlantic rainforest in south-eastern Brazil, Amblyomma aureolatum, A.
      brasiliense, A. incisum, A. ovale and Haemaphysalis juxtakochi were found
      questing on the vegetation. Most of the ticks recorded by a small, man-made dam
      on the forest border were A. dubitatum but a few A. brasiliense and A.
      cajennense, one A. incisum and one H. juxtakochi were also found. The seasonal
      activity of the ticks indicated that A. incisum and A. brasiliense had one
      generation/year. On the animal trails, most tick species and stages quested on
      the vegetation at a height of 30-40 cm above ground level. The questing larvae
      and adults of A. incisum tended to be found higher, however, with the greatest
      numbers recorded 40-50 cm (larvae) or 60-70 cm (adults) above ground level. Most
      of the adult ticks (81.1%-100%), nymphs (78.6%-100%) and larval clusters (100%)
      found on a forest trail remained questing at the same location over a 24-h
      period. Carbon-dioxide traps in the rainforest attracted <50% of the ticks
      observed questing on the nearby vegetation and, curiously, the CO2 traps set deep
      in the forest attracted far fewer ticks than similar traps set by the dam. The
      ecological relationships between the ticks, their hosts and the rainforest
      environment are discussed.

PMID- 19173778
TI  - Faunistic study of the sandflies (Diptera: Psychodidae) in an emerging focus of
      cutaneous leishmaniasis in Al Haouz province, Morocco.
AB  - The Moroccan province of Al Haouz is an emerging focus of human cutaneous
      leishmaniasis caused by Leishmania tropica. In an entomological investigation of
      three communes in the province (Ourika, Stti Fatma and Rhmate), 3440 sandflies
      were collected on sticky traps in 2005-2007. Of the six Phlebotomus species
      caught, Phlebotomus papatasi (13.3% of the total collection), P. sergenti (12.8%)
      and P. perniciosus (12.8%) were predominant, followed by P. longicuspis (7.9%),
      P. ariasi (2.6%) and P. alexandri (1.1%). All the other sandflies were
      Sergentomyia fallax (24.2%), S. minuta (22.0%) or S. dreyfussi (3.4%). The
      distribution of these species among the many biotopes, at varying altitudes (667
      1772 m), is discussed. When the variability of the P. sergenti populations in
      Ourika and Rhmate and those at two sites in northern Morocco (Taounate and
      Chefchaouene) was investigated by iso-enzyme analysis, seven polymorphic loci
      (PGI, PGM, HK, MDH1, ME, 6PGD and ACO) were identified. None of the investigated
      populations of P. sergenti was in Hardy-Weinberg equilibrium for all the
      polymorphic loci. The results indicate that the taxon known as Phlebotomus
      sergenti in Morocco does not have the genetic characteristics of a single
      species.

PMID- 19173779
TI  - The effects of different drying methods and sun exposure on the concentrations of
      deltamethrin in nets treated with K-O Tab tablets.
AB  - The method used to dry bednets after they have been treated with an insecticide
      solution may affect the levels of insecticide and the uniformity of the
      insecticide deposits on the dry nets. In an attempt to see how the drying method
      may affect the insecticide deposits on the dry net, and to select the best drying
      method, laboratory and field studies have recently been carried out (in the U.K.
      and Iran, respectively). Conventional polyester nets were each treated with a
      deltamethrin solution (made with one K-O Tab tablet in 500 ml water) and then
      dried, either while hanging vertically or laid horizontally on the floor, in the
      sun or shade. The concentrations of deltamethrin in 25-cm2 samples cut from the
      dry nets (from the inner folds, surface folds, and top and bottom of each net
      dried vertically, and from the upper and lower surfaces of each net dried
      horizontally) were then determined using high-performance liquid chromatography
      (HPLC). Drying the treated nets in the sun or the shade did not make a
      significant difference to deltamethrin concentrations on the nets. Mean
      deltamethrin concentrations were, however, higher on the lower parts of the nets
      that had been hung to dry vertically than on the upper parts of these nets, and
      greater on the upper surfaces of nets dried horizontally than on the lower
      surfaces of such nets. In general, the layers and folds of the nets that had been
      on the outside of the drying nets contained more deltamethrin than the inner
      folds. These patterns are consistent with the hypothesis that deltamethrin tends
      to accumulate at the points where the water from the insecticide solution
      evaporates from the drying nets and also, in the case of nets dried vertically,
      at the lower points of the drying nets (as the result of gravity). In order to
      obtain an even and adequate distribution of insecticide, it is therefore not
      necessary to dry the net in the shade. To achieve a uniform deposit of
      deltamethrin, the drying net should be folded as little as possible and dried
      quickly.

PMID- 19173780
TI  - Micrometry: a useful tool in the identification of intestinal coccidian
      parasites.

PMID- 19173781
TI  - The upper and lower airways: the epidemiological and pathophysiological
      connection.
AB  - The upper and lower airways do not exist as anatomically and functionally
      distinct areas. There are important relationships between both the nose and the
      paranasal sinuses and asthma. Both allergic rhinitis and rhinosinusitis may
      impact bronchial asthma. The patient with rhinitis should be observed carefully
      for the development of asthma, and those with asthma should be considered to have
      either rhinitis or rhinosinusitis.

PMID- 19173783
TI  - Allergic rhinoconjunctivitis and differential diagnosis of the red eye.
AB  - Red eye is a common presentation in clinical practice with conjunctivitis being
      the most common cause of red eye. Most commonly, conjunctivitis is infective
      (bacterial and viral) or allergic in origin although other forms of
      conjunctivitis including toxic and irritative conjunctivitis and conjunctivitis
      related to systemic conditions or dry eye are prevalent enough to warrant
      consideration in diagnosis. This article aims to provide a guide for generalists
      and allergists in the differential diagnosis of conjunctivitis allowing the
      inclusion of eye treatment into their current practice. With a discussion of
      important aspects to include in the patient history as well as a systematic guide
      to examination of the eye for generalists and allergists, this article provides a
      "plan of action" in the examination protocol for red eye patients. A differential
      diagnosis table and flowchart are provided as a useful chair-side reference for
      practitioners. With a particular focus on the more prevalent types of
      conjunctivitis, typical features, signs, and symptoms of each type are detailed.
      A general discussion of prognosis and treatment options and conditions that
      require ophthalmologic referral is included.

PMID- 19173782
TI  - Allergic rhinitis and asthma connection: treatment implications.
AB  - Treatment of patients with allergic rhinitis and asthma involves securing
      accurate diagnoses, avoidance measures, pharmacotherapy, and in some patients
      allergen immunotherapy, with consideration of immunomodulator therapy. At least
      20% of patients with asthma have evidence of gastroesophageal reflux (GERD) and
      others have laryngeal pharyngeal reflux (LPR) also referred to as supraesophageal
      reflux (SERD) or "atypical reflux." The scientific foundation of subcutaneous
      allergen immunotherapy (SCIT) includes generation of T-reg cells, which generate
      IL-10 and TGF-beta and suppress T(H2) and T(H1) lymphocyte responses. SCIT alone
      or even to a greater degree with omalizumab has been shown to reduce the extent
      of "facilitated allergen presentation" of allergen-IgE complexes binding to B
      lymphocytes, with the implication of reducing the extent of allergen presentation
      by B lymphocytes to T lymphocytes. In viewing the concept of the unified airway
      and the multiple approaches required for optimal patient care, asthma should be
      considered as a syndrome, which includes the concomitant conditions of allergic
      rhinitis and GERD (SERD or LPR) with the possibility of intermittent or chronic
      rhinosinusitis.

PMID- 19173784
TI  - Indoor allergens, environmental avoidance, and allergic respiratory disease.
AB  - Indoor allergen exposure to sources such as house-dust mites, pets, fungi, and
      insects plays a significant role in patients with allergic rhinitis and asthma.
      The identification of the major allergens has led to methods that can quantitate
      exposure, e.g., immunoassays for Der p 1 in settled dust samples. Sensitization
      and the development of allergic respiratory disease result from complex genetic
      and environmental interactions. New paradigms that examine the role of other
      environmental factors, including exposure to proteases that can activate
      eosinophils and initiate Th2 responses, and epigenetics, are being explored.
      Recommendations for specific environmental allergen avoidance measures are
      discussed for house-dust mites, cockroaches, animal dander, and fungi. Specific
      measures to reduce indoor allergen exposure when vigorously applied may reduce
      the risk of sensitization and symptoms of allergic respiratory disease, although
      further research will be necessary to establish cost-effective approaches.

PMID- 19173785
TI  - Allergen immunotherapy and asthma: efficacy, safety, and other considerations.
AB  - The efficacy of allergen immunotherapy (AIT) for allergic asthma is often debated
      despite multiple controlled trails and three meta-analyses that have established
      a significant effect on subjective and objective outcomes. Indications for AIT in
      allergic asthma include suboptimal control with medications, adverse effect of
      medications, and/or environmental control measures; patient's desire to avoid
      long-term pharmacotherapy; and presence of comorbid allergic conditions.
      Symptomatic asthma is a risk factor for AIT systemic reactions (SRs) and asthma
      should be controlled at the time of the AIT administration. The vast majority of
      studies in AIT for asthma have used single allergens although the majority of
      allergic patients in the United States are not monosensitized. There have been
      conflicting results in the limited number of studies that have investigated the
      effect of multiallergen AIT or as add-on therapy to asthmatic patients who are
      optimally controlled with medications and environmental controls. Several studies
      have suggested that AIT may prevent the development of asthma in subjects with
      allergic rhinitis and new allergen sensitizations. The recently updated Allergen
      Immunotherapy Practice Parameters lists possible prevention of asthma in patients
      with allergic rhinitis as one of the indications for AIT. Currently, subcutaneous
      immunotherapy is the only route with Federal Drug Administration approved
      formulations in the United States but sublingual immunotherapy is currently under
      investigation. This review examines the efficacy, safety, and preventive effects
      of these two routes of immunotherapy.

PMID- 19173786
TI  - The prevalence of nasal symptoms attributed to allergies in the United States:
      findings from the burden of rhinitis in an America survey.
AB  - Although the annual prevalence of physician-diagnosed hay fever has been
      previously reported, the prevalence of allergic rhinitis symptoms in the United
      States is uncertain. The purpose of this study was to estimate the prevalence of
      allergic rhinitis symptoms in the United States. A self-administered 10-item
      screening questionnaire regarding nasal symptoms was sent to representative
      households in the United States in January 2004. A total of 8,708 members (44.3%)
      reported nasal symptoms on > or =7 days in the past 12 months. The majority of
      these responders described their symptoms as seasonal or perennial allergies (n =
      5,944) compared with cold or flu only (n = 1,841), cold or flu and vasomotor
      rhinitis (n = 175), or vasomotor rhinitis only (n = 748). The prevalence of self
      reported seasonal and perennial allergic rhinitis symptoms on > or =7 days in the
      past 12 months was 30.2%, which corresponds to 89.6 million persons in the United
      States. The prevalence of self-reported physician-diagnosed seasonal or perennial
      allergic rhinitis with symptoms on > or =7 days was 22%, or approximately 65
      million persons nationwide. Among responders with a higher burden of nasal
      symptoms (> or =30 days), the prevalence of physician-diagnosed hay fever,
      allergic rhinitis, or nasal allergies was 11.9% of the total population. The
      prevalence of nasal symptoms attributed to rhinitis related to seasonal and
      perennial allergies in the United States ranged between 11.9 and 30.2% depending
      on duration of symptoms and physician diagnosis. Almost one-half of Americans
      experience troublesome nasal symptoms on at least 7 days throughout the year,
      with most attributing their symptoms to allergies.

PMID- 19173787
TI  - EG2 expressed by eosinophils as a clinically useful indicator of asthma.
AB  - The monitoring of airway inflammation is mandatory for the improved control of
      bronchial asthma. We previously reported that intracellular EG2 levels of
      eosinophils, a marker of bronchial asthma increased in asthma patients. In this
      study, we hypothesized that eosinophil EG2(+) expression increases during airway
      inflammation in asthmatic individuals. Eosinophil EG2(+) and percentage
      eosinophil EG2(+) with whole blood flow cytometry, eosinophil counts, serum total
      IgE, serum eosinophil cationic protein, eosinophil-derived neurotoxin, and
      percent of forced expiratory volume in 1 second/force vital capacity (FEV(1)/FVC)
      were measured in 33 asthmatic patients and 22 healthy volunteers. The
      relationships between these markers were evaluated. Comparisons were made on
      EG2(+) expression between attack and asymptomatic periods in six asthmatic
      patients. EG2(+) expression was significantly greater in the asthmatic patients
      than in healthy subjects. Furthermore, the EG2(+) expression showed a significant
      increase during attacks. EG2(+) expression inversely correlated with the
      FEV(1)/FVC. These results suggest that EG2(+) expression may be a useful clinical
      marker of airway inflammation in asthma.

PMID- 19173788
TI  - Gliadin-specific IgE in wheat-dependent exercise-induced anaphylaxis.
AB  - Food-dependent exercise-induced anaphylaxis is a unique form of food allergy.
      Recent studies indicate that gliadin is a major allergen in patients with wheat
      dependent exercise-induced anaphylaxis (WDEIA). We evaluated the value of serum
      gliadin-specific IgE in the diagnosis of WDEIA, as well as the characteristics
      and digestibilities of the IgE-binding components of gliadin. We analyzed 32
      adult subjects sensitized to wheat; 26 were asymptomatic sensitizers and 6 had
      WDEIA. Wheat flour and gliadin-specific IgE levels were measured, and
      corresponding receiver operator characteristics (ROC) curves were determined.
      Patients with WDEIA had higher levels of gliadin-specific IgE than patients
      without WDEIA (p = 0.003). The area under the ROC curve for gliadin-specific IgE
      was 0.872, which suggested this assay could be used as a supplementary test for
      the diagnosis of WDEIA. IgE immunoblot analyses of reactions to wheat and gliadin
      extracts were compared both with and without simulated gastric fluid (SGF) and
      intestinal fluid incubation (SIF). All six WDEIA patients had high IgE binding
      signals to 50 kDa of gliadin extract on IgE immunoblots. This binding was
      suppressed by SGF, although minimal inhibition was noted with SIF incubation.

PMID- 19173789
TI  - Oriental plane pollen allergy: identification of allergens and cross-reactivity
      between relevant species.
AB  - Pollen from different tree and grass species represent the greatest inducers of
      type I allergy worldwide. Oriental plane trees, as Platanus orientalis, are an
      important source of airborne allergens in cities of the southwest Asia and
      southeast Europe. This study was aimed to identify relevant allergens of P.
      orientalis pollen and to ascertain whether P. orientalis allergens have cross
      reactivity with related plane trees, such as Platanus acerifolia and Platanus
      occidentalis pollen components. Nineteen patients with a clinical history of
      reaction to P. orientalis pollen and a positive skin-prick test (SPT) to P.
      orientalis pollen extract were included in this study. Identification of IgE
      binding proteins in Platanus pollen extracts was elucidated by immunoblotting
      using sera from P. orientalis pollen-sensitive patients. Cross-reactivity studies
      among P. orientalis allergens and relevant species was evaluated by immunoblot
      inhibition and ELISA inhibition assays. All the patients were polysensitive and
      exhibited positive SPT to grass and tree pollen allergens. The IgE-binding
      pattern of P. orientalis pollen extract was well defined. The inhibition
      experiments showed that the capacity of P. occidentalis was greater than P.
      acerifolia pollen extract in preventing the reactivity of immobilized P.
      orientalis pollen extract with the IgE antibodies of patients. The 28-kDa
      molecule was the most frequent allergen among nine IgE-binding proteins of P.
      orientalis pollen. The IgE-reactive components of P. orientalis pollen showed a
      higher level of cross-reactivity with P. occidentalis pollen in comparison with
      P. acerifolia pollen.

PMID- 19173791
TI  - Use of olopatadine ophthalmic solution and reactivity of histamine skin testing.
AB  - The significant morbidity of allergic rhinitis and allergic conjunctivitis
      necessitates that diagnosis must be as accurate as possible. However, the very
      drugs used to treat allergic symptoms have been found to suppress histamine
      induced skin testing, making the diagnosis very challenging. Oral formulations of
      antihistamines are well known to diminish skin test reactivity, but ocular
      application has never been studied to our knowledge. This study was performed to
      evaluate whether olopatadine hydrochloride 0.2% ophthalmic solution suppressed
      histamine-induced wheals and flares on skin-prick testing. A randomized, double
      blinded, placebo-controlled, single-center, cross-over pilot study was performed
      that compared histamine-induced wheal and flare areas after 7-10 days of
      treatment with both olopatadine 0.2% ophthalmic solution and artificial tears,
      allowing for a 7- to 10-day washout period between medications. From a total of
      24 patients randomized, 21 subjects completed the study, 86% of whom were female.
      There were no statistically significant differences among both the wheal and the
      flare areas when comparing treatment with olopatadine and placebo, under the 5%
      significance level. Although characterized by a small sample size and a
      preponderance of female subjects, our data suggest that olopatadine does not
      suppress wheal and flare areas during allergy testing, and discontinuation in
      preparation for skin-prick testing does not appear to be necessary.

PMID- 19173790
TI  - Prevalence of IgE reactivities in mold-allergic subjects to commercially
      available fungal enzymes.
AB  - Fungi are important aeroallergens. However, fungal allergen sources of consistent
      quality for clinical testing are not readily available. Because some allergens
      have been identified as enzymes, we assessed the prevalence of IgE reactivity to
      commercially available fungal enzymes. The purpose of this study was to determine
      IgE antibody reactivity by radioallergosorbent assay (RAST) to commercially
      available fungal enzymes in mold-allergic individuals. Sera from 20 subjects with
      symptoms of respiratory allergies and skin test reactivity to 2 or more fungal
      allergens (4 conidial [imperfecti] fungi and/or 8 basidiomycetes) were selected.
      Controls were six atopic individuals with neither history of fungal allergy nor
      skin test reactivity to fungi. Seventeen commercial fungal enzymes were used as
      antigens to evaluate the subjects' IgE antibody reactivity by RAST. Sera from
      most fungus-allergic individuals showed substantial IgE antibody reactivity to
      enzymes; control sera showed little or no reactivity. The mean reactivity to all
      commercial enzymes of all subjects tested was RAST > or = 3% with only one
      exception. The most reactive fungal enzymes were invertase (bakers' yeast,
      Saccharomyces cerevisiae), cellulase (Trichoderma viride), and glucosidase
      (brewers yeast, S. cerevisiae) with mean binding of 14.6, 9.5, and 8.8%,
      respectively. Using RAST results with a combination of four enzymes from S.
      cerevisiae (brewers yeast glucosidase, bakers' yeast maltase, invertase, and
      invertase V), a sensitivity of 100% was shown for detecting mold-allergic
      patients. The studies suggest that fungal enzymes may be useful source materials
      for the identification of fungal allergens and may also provide readily available
      source materials to produce improved diagnostic and therapeutic reagents.

PMID- 19173792
TI  - Rapid diagnosis of bacterial sinusitis in patients using a simple test of nasal
      secretions.
AB  - Upper respiratory symptoms and sinusitis constitute a major reason for patient
      visits to their physician. The diagnosis of sinusitis is often made based on
      history and physical exam, but the accuracy of such diagnosis is questioned.
      Sinus films or CT scans are expensive. Obtaining pus from the middle meatus is
      impractical. We studied whether analysis of four easily measured substances
      (protein, pH, leukocyte esterase and nitrite) in nasal secretions could predict
      the presence or absence of bacterial sinusitis, as diagnosed by history combined
      with sinus x ray or CT. We enrolled 217 consecutive patients, aged 4-61 years,
      with clinically suspected bacterial sinusitis (duration of symptoms, 7-26 days),
      who had radiographic studies. All had their nasal secretions assayed using a
      simple rapid test. A clinical scoring system was developed to allow for a simple
      interpretation of test results of four assays in a single clinical score. All 52
      patients with scores of 0 or 1 were CT or x-ray negative for bacterial sinusitis.
      All 144 with scores of > or =4 were imaging study positive. Of the 21 patients
      (10%) with scores of 2 or 3, 14 were imaging study negative and 7 were positive.
      We concluded that combining these four separate assays on nasal secretion into
      one number, it is possible to rule in or rule out bacterial sinusitis in 90% of
      patients. This inexpensive, simple test can decrease the cost and help increase
      the accuracy of the diagnosis, thus improving the care of patients with bacterial
      sinusitis.

PMID- 19173793
TI  - Sinusitis and chronic progressive exercise-induced cough and dyspnea.
AB  - We present the case of a 47-year-old man with exercise-induced dyspnea, cough,
      chest tightness, and recalcitrant chronic rhinosinusitis. Evaluation revealed IgE
      sensitization to grass, tree, and weed pollen, no evidence of obstruction on
      spirometry, and a negative methacholine challenge. Diagnostic considerations
      included allergic and nonallergic rhinitis, asthma, aspirin-exacerbated
      respiratory disease, vocal cord dysfunction, extra-esophageal manifestations of
      acid reflux, and vasculitits. Further evaluation with sinus imaging,
      laryngoscopy, ambulatory pharyngeal pH testing, upper endoscopy, and bronchoscopy
      led to a diagnosis. Key issues surrounding the diagnostic and therapeutic
      approaches to this patient's condition are reviewed.

PMID- 19173796
TI  - [Image-guided target definition for external-beam partial breast irradiation
      after breast-conserving surgery].

PMID- 19173797
TI  - [Evaluation of the inhibitory effect of tripeptide tyroservatide on growth of
      human hepatocellular carcinoma using a hollow fiber assay].
AB  - OBJECTIVE: To investigate the inhibitory effect of tyroservatide (YSV) on growth
      of hepatocellular carcinoma cells. METHODS: In vitro effects of YSV on five human
      hepatocellular carcinoma cell lines were assayed by MTS. In vivo effects of YSV
      on 5 human hepatocellular carcinoma cell lines were assayed by hollow fiber tumor
      model. RESULTS: After treatment with YSV at a dose of 0.1 approximately 1.6
      mg/ml, the growth of the five cell lines was significantly inhibited in vitro
      compared with that of the control group (P < 0.05). Especially, YSL remarkably
      inhibited the growth of human hepatocellular carcinoma BEL-7402 cells, i.e. the
      cell growth was inhibited by 63.3% after treatment with YSL at 1.6 mg/ml. The
      hollow fiber tumor model demonstrated that YSL (320 microg x kg(-1) x d(-1) and
      640 microg x kg(-1) x d(-1)) treatment significantly inhibited the in vivo growth
      of the five cancer cell lines compared with that in the saline control (P <
      0.05). YSL showed the highest level of inhibition of human BEL-7402
      hepatocellular carcinoma cells, with an inhibitory index of 53.1% at 320 microg x
      kg(-1) x d(-1). CONCLUSION: As a new method, hollow fiber assay may be used to
      evaluate the inhibitory effect of drugs on different tumor cells in vivo,
      rapidly, accurately and economically. Our results provide an instruction and
      evidence for clinical use of YSV.

PMID- 19173798
TI  - [Preliminary study of DNA polymerase beta gene silencing by small interfering RNA
      in human gastric cancer BGC-823 cells].
AB  - OBJECTIVE: To study the influence of DNA polymerase beta (polbeta) gene silencing
      by small interfering RNA on biological behavior of human gastric cancer cell line
      BGC-823. METHODS: The siRNA eukaryotic expression vectors targeting polbeta gene
      were constructed and transfected into BGC-823 cells by liposome. Stable cell
      lines were screened with G418. The expression levels of polbeta mRNA and protein
      were detected by real time PCR and Western blot in the cells of each group. The
      proliferation of each group was detected by flow cytometry and tumorigenicity was
      determined in nude mice. RESULTS: The siRNA expression vector targeting polbeta
      gene was successfully constructed. The expression levels of polbeta mRNA and
      protein were significantly reduced in the experimental group transfected with
      siRNA expression vectors targeting polbeta, and the silencing effect of pRNAT
      U6.1-sipolbeta2 (suppression degree was 83%) was stronger than that of pRNAT-U6.1
      sipolbeta1 (depression degree is 56%). Compared with irrelevant siRNA control
      group, empty vector control group and untransfected group, the ratio of G0/G1
      cells was increased, proportion of S phase cells and cell proliferation were
      decreased in the experimental group 1 cells transfected with pRNAT-U6.1
      sipolbeta1 (P < 0.05). On the contrary, the ratio of G1/G0 was decreased,
      proportion of S phase cells and cell proliferation was increased in the
      experimental group 2 cells transfected with pRNAT-U6.1-sipolbeta2 (P < 0.05).
      CONCLUSION: The siRNA expression vectors targeting DNA polymerase beta gene can
      significantly inhibit the expression of polbeta mRNA. Neither high nor extremely
      low expression of polbeta is beneficial to maintain the cellular physiological
      functions. The expression of polbeta silenced to a proper level by siRNA may play
      an important role in inhibiting tumorigenesis.

PMID- 19173799
TI  - [hTERT promoter enhances the radiosensitivity to gene-radiation therapy of human
      laryngeal carcinoma transplanted in nude mice].
AB  - OBJECTIVE: To explore the therapeutic efficiency of human telomerase reverse
      transcriptase promoter (hTERTp) mediated horseradish peroxidase (HRP) catalyzed
      effects of indole-3-acetic (IAA) on laryngeal squamous cell carcinoma with
      different radiosensitivity in vivo. METHODS: Human laryngeal squamous cell
      carcinoma Hep-2 and Hep-2R cells were transplanted into nude mice. After growing
      to about 30 approximately 50 mm3, the tumor-bearing mice were randomly divided
      into eight groups: Hep-2 line: combined group (A), gene group (B), radiation
      group (C) and blank group (D); Hep-2R line: combined group (AR), gene group (BR),
      radiation group (CR) and blank group (DR). The phTERTp-HRP was delivered by
      intratumoral injection and the IAA by intraperitoneal injection, combined with 2
      Gy daily radiation to a total dose of 30 Gy. The tumor volume was recorded. The
      cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated
      dUTP nick end-labeling (TUNEL) assay. The expression of HRP protein was detected
      by AP immunohistochemisty. RESULTS: The tumor growth of combined groups was
      attenuated significantly and the tumor volume of Hep-2R blank group was the
      largest. The inhibition rate of each group was: A: 54.8%, B: 10.0%, C: 31.9%; AR:
      52.7%, BR: 24.8%, CR: 17.0%. In the combined groups, necrosis and apoptosis of
      tumor cells were observed under the light microscope and the apoptotic index [A
      (16.6 +/- 1.3)% vs. AR (17.6 +/- 1.3)%] of tumor cells was highest (P < 0.05).
      The HRP protein expression of BR (33.3 +/- 8.9)% was higher than that of B (21.9
      +/- 5.7)%, which was directly up-regulated in the tumors (45.0% vs. 54.8%, P <
      0.05) after radiation. CONCLUSION: In the Hep-2- and Hep-2R-transplantation
      tumors in nude mice, hTERTp can be induced by radiation and enhance the
      expression of horseradish peroxidase (HRP) gene according to telomerase activity.
      hTERTp-HRP/IAA system, which has synergistic effects with radiation and inhibits
      the tumor growth by induction of apoptosis and necrosis, may be a new gene
      radiation strategy for the treatment of laryngeal carcinoma.

PMID- 19173800
TI  - [Feasibility of apoptosis-imaging agent 99mTc-HYNIC-annexin V in early assessment
      of chemotherapeutic effect on tumor models].
AB  - OBJECTIVE: To evaluate if 99mTc-HYNIC-annexin V may be used to detect the early
      chemotherapeutic effect and to determine the best timing for detecting apoptosis
      in vivo. METHODS: Annexin V was labeled with 99mTc using HYNIC as a bifunctional
      agent. Normal Kunming mice received inoculation of Ehrlich ascites cells into the
      right upper limb. After the tumor reached 1 cm in diameter, the mice were
      randomly divided into saline treatment group as control and cyclophosphamide (150
      mg/kg injected intraperitoneally) treatment group. 99mTc-HYNIC-annexin V was
      injected intravenously at 1 h and 24 h after treatment. Region of interest
      technique (ROI) from the SPECT images taken at different time was used to get the
      ratio of tumor/limb in each group. TUNEL staining was used to detect apoptotic
      cells and the rates of positive stained cells were calculated. RESULTS: After
      treatment with saline, only little amount of the radiolabeled tracer could be
      seen in the tumor and showed weak image of the tumor. But after 24 h of treatment
      with cyclophosphamide, clear image on the tumor could be seen. 24 h after the
      treatment of cyclophosphamide, the ratio of tumor/limb was (6.27 +/- 0.24) which
      was much higher than that at 24 h after treatment with saline (2.36 +/- 0.18) and
      that at 1 h after cyclophosphamide treatment (4.00 +/- 0.38). At 24 h after
      cyclophosphamide treatment, TUNEL staining showed a significantly higher rate of
      apoptotic cells in the mice. CONCLUSION: 99mTc-HYNIC-annexin V can be used as an
      apoptosis-imaging agent to detect and evaluate the early curative effect after
      chemotherapy. The effective detection of apoptotic response in tumor with 99mTc
      HYNIC-annexin V requires a 24 h interval after chemotherapy. SPECT images can be
      obtained at 60 min after injection of the imaging agent. It suggests that 99mTc
      HYNIC-annexin V may become a promising agent for apoptosis-imaging in clinical
      application.

PMID- 19173801
TI  - [Down-regulation of TopI by RNA interference reduces the drug-sensitivity of
      small cell lung cancer cell lines to topotecan].
AB  - OBJECTIVE: To investigate the expressions of TopI gene in small cell lung cancer
      cell line H446, and explore the influence of TopI on the chemosensitivity of the
      cell line to topotecan (TPT). METHODS: Western blot was performed to detect the
      TopI expression in H446 cells. Lipofectamine 2000 was used for the transient
      transfection of H446 cells by siRNA, and the transfection efficacy was detected.
      TopI mRNA was analyzed by quantitative RT-PCR and TopI protein was detected by
      Western blot to selected effective siRNA. The drug-sensitivity to topotecan (TPT)
      was evaluated by MTT assay. RESULTS: TopI gene was expressed in H446 cells.
      Lipofectamine 2000 mediated the siRNA effectively (88.67%). Compared with its
      parental cells, RT-PCR results showed that TopI mRNAs in transfected cells were
      reduced by (95.7 +/- 1.6)%, (90.8 +/- 1.6)%, (96.1 +/- 2.7)% and (96.3 +/- 1.8)%,
      respectively, and decreased significantly at protein level. By MTT assay, the
      inhibition rate of TPT to H446 cells transfected by siRNA was lower than that of
      control group at same concentrations (P < 0.01). CONCLUSION: siRNAs can silence
      the expression of TopI and decrease the drug-sensitivity of H446 cells to TPT.

PMID- 19173802
TI  - [Insulin/PI3K signalling pathway regulates the expression of survivin in liver
      cancer HepG2 cells].
AB  - OBJECTIVE: To determine the expression level changes of survivin, a inhibitor of
      apoptosis protein, followed by activation of insulin receptors in human
      hepatocellular carcinoma HepG2 cell line, and to investigate the signalling
      pathway involved in the regulation. METHODS: Human hepatocellular carcinoma HepG2
      cells were treated with insulin alone or pre-treated with LY294002, a specific
      inhibitor of PI3K signalling pathway, to determine whether blocking PI3K
      signaling can attenuate the up-regulation of survivin expression. Real time RT
      PCR and Western blot analysis were used to measure survivin mRNA and protein
      changes before and after treatment, respectively. RESULTS: Without serum
      supplement, HepG2 cells expressed a small amount of survivin. Insulin induced
      survivin expression in a dose- and time-dependent fashion. Survivin expression
      was blocked if cells were pre-treated with LY294002 prior to insulin stimulation.
      CONCLUSION: Insulin induces survivin expression via PI3K signalling pathway,
      suggesting that to interfere the key gene in this signalling pathway may block
      survivin expression, therefore, promoting apoptosis in hepatocellular carcinoma
      cells.

PMID- 19173804
TI  - [Expressions of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma and their
      relationship with clinicopathological factors].
AB  - OBJECTIVE: The purpose of this study was to explore the clinical significance of
      expression of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma. METHODS: Semi
      quantitative reverse transcriptive polymerase chain reaction (RT-PCR) was used to
      analyze the mRNA expression levels of the three genes in tumor tissues from 60
      patients with primary breast cancer and normal breast tissues of 30 cases. The
      relationship between gene expression and clinicopathological factors were
      analyzed and determined. RESULTS: The relative expression levels (gray scale
      ratio between target gene and internal reference gene) of Fas, CTLA-4 and RhoBTB2
      genes in breast carcinoma tissues were 0.699 +/- 0.285, 1.045 +/- 0.302 and 0.625
      +/- 0.160, respectively. In the normal breast tissues, they were 0.502 +/- 0.178,
      0.418 +/- 0.140 and 0.843 +/- 0.218, respectively. There were statistically
      significant differences of the expression of those three genes between carcinoma
      tissues and normal breast tissues (P < 0.01). The expression level of Fas in
      carcinoma tissues was significantly higher in lymph node matastasis positive
      patients (0.782 +/- 0.313) than that in node-negative patients (0.557 +/- 0.146,
      P < 0.01). The expression level of CTLA-4 gene in carcinoma tissues was lower in
      II stage patients (0.978 +/- 0.330) than that in III stage patients (1.134 +/-
      0.240, P < 0.05). The expression level of RhoBTB2 gene was lower in invasive
      ductal carcinoma (0.597 +/- 0.157) than that in invasive lobular carcinoma (0.717
      +/- 0.145, P < 0.05). There were no correlations of expression of the three genes
      at mRNA level and age, ER, PR, HER2 status and survival time. Furthermore, no
      correlation was seen among the three genes expression (P > 0.05). CONCLUSION: The
      expression of all the three genes at mRNA level is involved in genesis and
      progression of breast cancer. There exist correlations between Fas expression and
      axillary lymph node matastasis, CTLA-4 expression and disease stage, and RhoBTB2
      expression and pathological type of breast cancer.

PMID- 19173805
TI  - [Analysis of serum biomarkers of ovarian epithelial cancers based on 2-DE DIGE
      and MALDI TOF/TOF].
AB  - OBJECTIVE: To find new serum tumor markers for ovarian epithelial cancers by 2-DE
      DIGE and MALDI-TOF/TOF proteomic methods, in order to improve the diagnostic
      sensitivity and specificity. METHODS: Serum samples from 103 cases of ovarian
      epithelial cancers, 60 cases of healthy women, 63 cases of benign ovarian tumors
      and 63 cases of benign pelvic diseases were collected. Sera of 20 cases of
      ovarian epithelial cancers (A), 20 cases of ovarian benign tumors (B), 20 cases
      of pelvic benign diseases (C) and 20 cases of health control (D) were matched by
      age and pooled, respectively. After depletion of high abundance serum albumin and
      IgG, the samples were assayed by 2-DE DIGE. The test was repeated three times.
      Analysis with DeCyder software revealed significant differential protein spots
      which were identified by MAIDI-TOF/TOF. Western blot and ELISA were used to
      validate the candidate serum markers. RESULTS: 1) There were 41 proteins having
      significant differences between the groups. MAIDI-TOF/TOF successfully identified
      28 proteins. Haptoglobin (Hp) was the most significantly up-regulated protein,
      and transferrin (Tf) was the most significantly down-regulated protein. 2)
      Western blot and ELISA proved that there were significant differences in Hp and
      Tf between ovarian epithelial cancers and normal controls (P = 0.000), between
      ovarian epithelial cancers and ovarian benign tumors (P = 0.000), between ovarian
      epithelial cancers and benign pelvic disease sera (P = 0.000). 3) CA125 + Hp + Tf
      combined detection of ovarian cancer had higher sensitivity and specificity than
      CA125, Hp or Tf detection alone. CONCLUSION: Hp and Tf are differently expressed
      in the sera of patients with ovarian epitheliual cancers. They can be used as
      serum biomarkers for ovarian epithelial cancers. CA125 + Hp + Tf combined
      detection may improve the sensitivity and specificity of diagnosis of ovarian
      epithelial cancers.

PMID- 19173806
TI  - [Induction of dendritic cells from intra-operative lost blood and their effects
      on CIK against liver cancer cells in vitro].
AB  - OBJECTIVE: To investigate the practical possibility of inducing dendritic cells
      (DCs) from mononuclear cells in the lost blood during operation of hepatocellular
      carcinoma (HCC) patients, and attempted to find a new source of precursor cells
      for the personalized immunotherapy based on DCs. METHODS: Collected lost blood
      during hepatectomy from 9 HCC patients and human cord blood from 8 cases of
      healthy donors undergoing caesarean section. Their mononuclear cells were divided
      into monocytes and nonadherent lymphocytes. RhGM-CSF and rhIL-4 were administered
      to induce the monocytes differentiation into DCs, and then loaded with different
      antigens (lysate antigen of autologous liver cancer cells and cell line SMMC-7721
      cells). The lymphocytes were induced into cytokine-induced killer cells (CIK)
      with IL-2, CD3-Ab, gamma-IFN and PHA. MTT assay was performed to detect the
      proliferation rate of T lymphocytes mediated by DC and the cytotoxicity of CIK to
      liver cancer cells. RESULTS: DCs induced from monocytes of the intra-operative
      lost blood possessed typical morphology and phenotypes. Compared with the DCs
      from cord blood, the DCs from intra-operative lost blood expressed lower level of
      surface markers, but both could effectively induce proliferation of CIK and
      enhance the cytotoxicity of activated CIK against liver cancer cells at similar
      levels. When the DCs from lost blood and their counterpart from cord blood were
      both loaded with autologous tumor cell antigen, the proliferation rates of CIK
      were (388.9 +/- 137.3)% and (315.1 +/- 44.5)%, respectively, and the killing
      rates against tumor cells were (87.1 +/- 8.0)% and (90.0 +/- 5.1)%, respectively.
      When the two similar DC groups were loaded with lysate antigen of SMMC-7721
      cells, the proliferation rates of CIK were (239.9 +/- 48.7)% and (226.3 +/-
      32.3)%, respectively, and the killing rates against tumor cells were (76.4 +/-
      7.9)% and (81.1 +/- 4.3)%, respectively. There were no significant differences
      between those two DC groups. The data also showed that the proliferation and
      cytotoxicity of CIK induced by DCs loaded with autologous antigen were higher
      than that of DCs loaded with SMMC-7721 antigen. CONCLUSION: Mononuclear cells
      separated from intra-operative lost blood of HCC patients can be induced into
      mature DCs, which can effectively activate CIK and significantly increase its
      killing effect on the liver cancer cells, and may become a new source of DCs to
      study and develop vaccines for clinical application.

PMID- 19173807
TI  - [Correlation between SUV of (18)F-FDG PET-CT and the expression of GLUT1, MVD and
      Ki67 in non-small cell lung cancer].
AB  - OBJECTIVE: To investigate the correlation between 18F-FDG standard uptake value
      (SUV) and expression of GLUT1, MVD and Ki67 in non-small cell lung cancer
      (NSCLC). METHODS: Thirty-three patients with non-small cell lung cancer received
      preoperative 18F-FDG PET-CT examination and underwent surgery. The expression of
      GLUT1, MVD and Ki67 were detected by immunohistochemstry. The correlation between
      the SUV of 18F-FDG PET-CT and the immunohistochemical results of the three above
      mentioned parameters was analyzed. RESULTS: Of the 33 NSCLC patients, 21 were in
      stage I, 4 in stage II and 8 in stage IIIa. Positive expression of GLUT1 was
      found in 22 cases (66.7%, 12 adenocarcinomas and 10 squamous cell carcinomas),
      and negative expression in 11 cases (10 adenocarcinomas and 1 squamous cell
      carcinoma). Twenty-four patients (72.7%) showed positive expression of Ki67 (13
      adenocarcinomas and 11 squamous cell carcinomas), and other 9 (adenocarcinomas)
      had negative expression. The positive expression rate of CD34 in this series was
      100.0% with a mean MVD of 12.6 +/- 2.9. CONCLUSION: SUV of 18F-FDG PET-CT is
      linearly correlated with the expression of GLUT1, but not with the expression of
      Ki67 or MVD. The expression of GLUT1, Ki67 and CD34 is not correlated with tumor
      size and lymph node metastasis.

PMID- 19173808
TI  - [Clinicopathological observation on 2 cases of nasal-type NK/T-cell lymphoma in
      the esophagus].

PMID- 19173809
TI  - [Single nucleotide polymorphism analysis of germline MSH6 gene mutations in
      Chinese hereditary non-polyposis colorectal cancer probands].

PMID- 19173810
TI  - [Analysis of the diagnosis and treatment of cervical minimal deviation
      adenocarcinoma].
AB  - OBJECTIVE: To analyze the characteristics of cervical minimal deviation
      adenocarcinoma (MDA) and the methods of diagnosis and treatment. METHODS: A
      retrospective study was carried out to evaluate the clinical and pathological
      data of 15 patients with MDA treated from 1992 to 2007. RESULTS: The average age
      of the 15 patients was 42.3 years. The main symptoms were increased discharge and
      irregular vaginal bleeding. Preoperative Pap smears showed adenocarcinoma in 3
      cases (27.3%). The diagnosis of MDA was confirmed in 8 cases by cervical punch
      biopsies (53.3%) and 2 cases by conization. Several cysts were noted in sections
      of the endocervix. Microscopic examination showed glands irregular in size and
      shape. However, the deviation of tumor cells was minimal. Immunohistochemistry
      revealed positive expression of CEA and alpha-SMA. The mean follow-up time was
      51.0 months. The overall 5-year survival rate was 85.7%. Four cases experienced
      recurrence in the vagina and pelvis at 2 years after operation. Three cases died
      of the disease relapse with an average survival time of 36.3 months. CONCLUSION:
      Cervical minimal deviation adenocarcinoma is rare, with minimal deviation of cell
      shape from the normal cervical cells and difficult in diagnosis. A deep biopsy or
      conization is necessary when punch biopsy is not sufficient for diagnosis.
      Immunohistochemistry is helpful to make an accurate diagnosis. Surgery is the
      first choice for cervical minimal deviation adenocarcinoma. Radiotherapy and/or
      chemotherapy should be given if needed. The prognosis can be improved if a proper
      treatment plan is carried out.

PMID- 19173811
TI  - [Prognostic implication of common bile duct infiltration in adenocarcinoma of the
      ampulla of Vater after pancreaticoduodenectomy].
AB  - OBJECTIVE: To investigate the prognostic implication of common bile duct
      infiltration in the adenocarcinoma of the ampulla of Vater after
      panreaticoduodenectomy. METHODS: A retrospective study was conducted on clinical
      manifestation, pathological behavior and survival data in 102 patients with
      Vater's ampulla adenocarcinoma, who underwent pancreaticoduodenectomy from Jan
      1980 to Dec 2003. The result of patients with the common bile duct infiltration
      were compared with that of those without. RESULTS: There were 42 cases in stage I
      (41.2%), 32 in stage II (31.3%), 27 in stage III (26.5%), and 1 in stage IV
      (1.0%). As for T stage: 9 cases in stage T1 (8.8%), 40 in T2 (39.2%), 25 in T3
      (24.5%), and 28 in T4 (27.5%). As regarding to N stage: 76 cases in stage N0
      (74.5%) and 26 in N1 (25.5%). Of these 102 cases, microscopic infiltration in the
      common bile duct (25.0%) was identified in 26 cases. A significant difference was
      observed between the patients with bile duct infiltration and those without, in
      the proportion of pancreatic medullae infiltration: 84.6% (infiltration group)
      versus 34.2% (non-infiltration group, P < 0.001). Twenty-five cases (24.5%) had
      recurrence and/or metastases postoperatively, with a median survival of 20 months
      (range, 2 to 93 months). The overall median survival of the whole group was 46.0
      months (2 approximately 192 months), with a significant difference between the
      common bile duct infiltration group (36 months) and the non-infiltration group
      (49 months, P = 0.0061). The median non-recurrence survival of the whole group
      was 43 months (2 approximately 192 months), and a significant difference was
      observed between the common bile duct infiltration group (35 months) and non
      infiltration group (47 months, P = 0.0002). CONCLUSION: If the adenocarcinoma of
      the Vater's ampulla infiltrated the common bile duct, the invasion to the
      pancreatic medulla is likely developed, and usually with a poor non-recurrence
      and overall survival. Therefore, postoperative chemotherapy/radiotherapy is
      suggested.

PMID- 19173813
TI  - [DNCE regimen for treatment of refractory or relapsed aggressive and highly
      aggressive non-Hodgkin lymphoma].
AB  - OBJECTIVE: To evaluate the efficacy and safety of DNCE [DXM, navelbine (NVB), DDP
      and Vp-16] regimen and DICE [dexamethasone (DXM), ifosfamide (IFO), cisplatin
      (DDP) and etoposide (Vp-16)] regimen in the treatment of refractory or relapsed
      aggressive and highly aggressive non-Hodgkin lymphoma (NHL). METHODS: A total of
      69 patients with histopathologically proved advanced aggressive and highly
      aggressive NHL were randomized into trial group (32 patients treated with DNCE
      regimen) and control group (37 patients treated with DICE regimen). The control
      group was given DICE regimen: DXM 20 mg, iv d1 approximately d4; IFO 1 g/m2), iv
      d1 approximately d4; Mesna 400 mg, iv q8h, d1 approximately d4; DDP 25 mg/m2, iv
      d1 approximately d4; Vp-16 100 mg/m2, iv d1 approximately d4; one cycle for 21
      approximately 28 days. The trial group was given DNCE regimen: DXM 20 mg, iv d1
      approximately d4; NVB 25 mg/m2, iv d1 and d5; DDP 25 mg/m2, iv d1 approximately
      d4; Vp-16 100 mg/m2, iv d1 approximately d4; one cycle for 21 approximately 28
      days. Each patient completed at least 2 cycles of treatment. RESULTS: A better
      efficacy was shown in the complete response rate, partial response rate, and
      total response rate between DNCE and DICE groups (18.8% vs. 10.8%, 37.5% vs.
      35.1%, and 56.3% vs. 45.9%, respectively), but the differences were statistically
      non-significant (P > 0.05). The 1-, 3-, and 5-year survival rates were not
      significantly increased in DNCE group compared with that in DICE group (86.5% vs.
      87.5%, 58.3% vs. 63.2%, 42.9% vs.38.5%, respectively, P > 0.05). The major side
      effects were leucopenia, thrombocytopenia, and nausea in both groups. The bone
      marrow depression in DNCE group was significantly slighter than that in the DICE
      group (P < 0.05). CONCLUSION: The efficacy of DNCE regimen is as good as DICE
      regimen, and the bone marrow toxicity is less severe in DNCE group than that in
      DICE regimen. Therefore, the DNCE regimen is an effective second-line salvage
      regimen for the treatment of refractory or relapsed aggressive and highly
      aggressive non-Hodgkin lymphoma.

PMID- 19173815
TI  - [Postoperative three-dimensional conformal radiotherapy for resected non-small
      cell lung cancer].
AB  - OBJECTIVE: To investigate the association between survival and postoperative
      three-dimensional conformal radiotherapy (3DCRT) in patients with resected non
      small cell lung cancer (NSCLC). METHODS: Eighty-four patients were treated with
      surgery and postoperative 3DCRT for NSCLC. Sixty-five (77.4%) patients received
      lobectomy, and 19 (22.6%) received pneumonectomy. Fifty-four (64.3%) patients
      achieved R0 resection and 30 cases (35.8%) received R1/R2 resection. Fifty-two
      patients were of stage IIIA and 24 patients were of stage IIIB. Photon energy of
      6 MV was used for all the patients. The median 3DCRT dose was 60 Gy (40 - 70 Gy)
      with a fraction size of 2 Gy. Thirty-seven patients received median 3 cycles of
      adjuvant chemotherapy. The median follow-up was 35.5 months for survivors.
      RESULTS: The overall 3-year survival rate was 58.6%, and the 4-year overall
      survival rate was 43.9%. Of the 43 patients who had treatment failure, only 8
      (9.9%) patients showed intrathoracic recurrence, but 38 (46.9%) patients had
      distant metastasis. The univariate analysis for all patients showed that sex,
      age, weight loss, tumor size, pathology and stage were not correlated with
      prognosis. R1/R2 resection was associated with a significantly worse survival.
      Toxicities were acceptable, with 9 (11.1%) patients appeared higher than NCI CTC
      grade 2 radiation pneumonitis. CONCLUSION: In a population-based cohort,
      postoperative 3DCRT for NSCLC provides a good prognosis, and the radiation
      related pneumonitis is acceptable.

PMID- 19173816
TI  - [Combination of docetaxel and capecitabine for the treatment of anthracycline
      resistant advanced breast carcinoma].
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of docetaxel and capecitabine
      combination in the treatment of anthracycline-resistant advanced breast
      carcinoma. METHODS: Forty-three patients with anthracycline-resistant advanced
      breast carcinoma were treated with docetaxel combined with capecitabine between
      January 2002 and November 2004. Docetaxel was administered intravenously at a
      dose of 75 mg/m(2) on D1, and oral intake of capecitabine at a dose of 1600 mg/d
      on D1 to D14, every 21 days as a cycle. The median number of cycles was 4 (range,
      4 approximately 6 cycles). RESULTS: All the 43 patients had a mean follow-up of
      15 months. The overall response rate was 62.8%, with a complete response rate of
      20.9% and partial response rate of 44.2%. The median survival time was 15 months
      with a median time to progression of 7.5 months. The one-year and 2-year survival
      rates were 62.8% and 41.9%, respectively. The quality of life was improved in all
      patients. The major toxicity and adverse effects were gastrointestinal reaction
      and hematological toxicity. CONCLUSION: The combination of docetaxel and
      capecitabine for the treatment of anthracycline-resistant advanced breast
      carcinoma is effective, safe and tolerable.

PMID- 19173817
TI  - [Analysis of severe complications after transcatheter arterial chemoembolization
      for primary hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the cause and treatment as well as prevention measures
      of rarely occurring severe complications after transcatheter arterial
      chemoembolization (TACE) for primary hepatic carcinoma. METHODS: 573 consecutive
      patients with primary hepatic carcinoma underwent a total of 1252 TACE procedures
      from January 2005 to July 2007. All the patients who developed complications
      after TACE received imaging and biochemical examinations. The cause, treatment
      and preventive measures of the complications in the 573 cases were analyzed.
      RESULTS: There were upper gastrointestinal hemorrhage in 3 cases, hepatic failure
      in 4, pulmonary embolism in 1, cholecystitis in 4, hepatic encephalopathy in 2,
      gastric perforation in 1, and intrahepatic biloma in 2 cases. Two patients died
      of the complications: 1 of hepatic failure and 1 of gastric perforation.
      CONCLUSION: The rarely occurring severe complications after transcatheter
      arterial chemoembolization for primary hepatic carcinoma is correlated with poor
      hepatic function and portal hypertension before therapy, overdose and reflux of
      chemotherapeutic agents or allotopic chemoembolism, etc. It can be reduced or
      prevented through careful selection of proper cases before the treatment, close
      observation, and protection of hepatic function and gastric mucosa after
      treatment.

PMID- 19173818
TI  - [Diagnosis and treatment of pancreatic metastasis from renal cell carcinoma].
AB  - OBJECTIVE: Pancreatic metastasis from renal cell carcinoma (RCC) is a rare event
      and has not been reported in our country. We report a series of 3 patients with
      metastatic RCC to the pancreas after radical nephrectomy at our institution. The
      published reports in the literature were reviewed, and the diagnosis, treatment
      as well as prognosis of this rare event were discussed. METHODS: The data of 3
      RCC patients with metastasis to the pancreas were reviewed retrospectively,
      including radical nephrectomy, metastatic interval, the second and third surgical
      removal. Survival of the three patients was analyzed and the reports in the
      literature were compared as well. RESULTS: The average interval from radical
      nephrectectomy to the comfirmed pancreatic metastasis was 6.6 years (range, 1.2
      to 12 years). The pathological stage revealed T2N0M0 (n = 2) or T3N0M0 (n = 1),
      with right-sided tumor in 2 patients and left side in 1. One patient was
      asymptomatic, while the other two cases were symptomatic at presentation,
      including upper abdominal pain, weight loss, slight xanthochromia of the skin and
      titillation, clay stool (n = 1); irregular fever, weight loss and jaundice (n =
      1). All pancreatic metastases were hypervascular on arterial stage of CT imaging.
      One patient had only a solitary pancreatic metastasis (n = 1), the another showed
      two metastatic lesions (n = 1), the third one had multiple lesions (n = 1).
      Surgical removal was accomplished in 2 patients: including pylorus-preserving
      pancreaticoduodenectomy in one, and pylorus-preserving pancreaticoduodenectomy
      together with partial tail resection in another one. The third one only received
      interventional therapy due to widespread extrapancreatic metastasis, and died of
      disseminated disease 11 months after the therapy. One of the above two surgically
      treated patients underwent the second removal due to local recurrence 2.5 years
      after the first removal of pancreatic metastasis. These two patients were still
      alive after follow-up of 8.6 years and 16.1 years, respectively. CONCLUSION:
      Renal cell carcinoma is an unpredictable tumor that may demonstrate very delayed
      metastasis even from early-stage of the disease. The pancreas is a rare site of
      metastasis from renal cell carcinoma. We advocate careful long-term follow-up of
      patients with a history of RCC. Aggressive surgical management of pancreatic
      metastatic lesions may provide a chance of long-term survival.

PMID- 19173819
TI  - [Resection of liver caudate lobe hepatocellular carcinoma via right-side approach
      to dissect the third hepatic hilum].

PMID- 19173820
TI  - [Introduction and consideration of the anti-cancer drug evaluation strategy in
      Europe and America].

PMID- 19173821
TI  - [Stem cell-targeted therapy--a new strategy for cancer treatment].

PMID- 19173822
TI  - [Antitumor effect of RNA interference on non-small cell lung cancer in vivo].
AB  - OBJECTIVE: To investigate whether chemically synthesized double-stranded RNA
      (dsRNA) targeting epidermal growth factor receptor (EGFR) can induce gene
      silencing in non-small cell lung cancer (NSCLC) cells in vivo. METHODS: The NSCLC
      cell line SPC-A1 was transfected with EGFR sequence-specific dsRNA formulated
      with Lipofectamine 2000. SPC-A1 cells (1 x 10(7)/ml) in 200 microl were injected
      s.c. into the left flank area of the athymic nude mice to establish a tumor
      bearing nude mouse model. To calculate the tumor growth inhibition rate by
      measuring the diameter and the weight of the tumor. Immunohistochemistry and
      Western blot were used to monitor the reduction of EGFR protein production. Real
      time RT-PCR was used to detect the silencing of the EGFR mRNA level. RESULTS: The
      EGFR sequence specific dsRNA (dsRNA-EGFR) significantly inhibited the tumor
      growth in vivo. The tumor growth inhibition rate was 75.0%. The dsRNA-EGFR
      sequence specifically silenced EGFR with 53.6% of down-regulation of EGFR protein
      production and 32.3% of silencing of EGFR mRNA level. CONCLUSION: dsRNA-EGFR show
      a blockbuster effect in down-regulation of EGFR mRNA level and protein
      production, and inhibition of tumor growth in vivo.

PMID- 19173823
TI  - [Inhibitory effects of a combination of rmhTRAIL and gemcitabine on human non
      small cell lung cancer cell line NCI-H460 cells in vitro and in vivo].
AB  - OBJECTIVE: To evaluate the inhibitory effects of recombinant mutant tumor
      necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) combined with
      chemotherapeutic agent gemcitabine (GEM) on human lung cancer cell line NCI-H460
      cells in vitro and in vivo. METHODS: MTT was used to evaluate the cytotoxic
      effects of rmhTRAIL and GEM either used alone or in combination treatment on NCI
      H460 cells. BAL B/c nude mice were transplanted with NCI-H460 tumor. The tumor
      bearing nude mice were randomly divided into 6 groups (n = 6): negative control
      group (to be injected intraperitoneally with normal saline); rmhTRAIL group; GEM
      group; rmhTRAIL plus GEM group; GEM plus DDP group; rmhTRAIL plus GEM andDDP
      group. The tumor size was measured every 3 - 4 days. Twenty one days after the
      administration of different drugs the mice were killed and the tumors were taken
      out and weighed. RESULTS: The growth inhibition of NCI-H460 cells was dose
      dependent after exposure to rmhTRAIL, GEM alone or together. The combination of
      rmhTRAIL and GEM showed a synergistic inhibitory effect at different
      concentrations. The relative tumor volume of rmhTRAIL group, rmhTRAIL plus GEM
      group, GEM plus DDP group and rmhTRAIL plus GEM and DDP group were 4.75 +/- 3.04,
      2.53 +/- 1.25, 4.52 +/- 2.87, and 1.69 +/- 0.97, respectively, all significantly
      smaller than that of the negative control group (8.82 +/- 5.62, P < 0.05 or P <
      0.01). The tumor weight of these four groups were (2.23 +/- 0.29) g, (1.12 +/-
      0.77) g, (2.51 +/- 0.87) g, and 0.60 +/- 0.18 g, respectively, all significantly
      less then that of the negative control group (4.71 g +/- 0.97 g, all P < 0.01).
      Both the relative tumor volume and tumor weight of rmhTRAIL plus GEM group were
      significantly smaller than those of either rmhTRAIL group or GEM group (P < 0.05
      and P < 0.01, respectively). Both the relative tumor volume and tumor weight of
      rmhTRAIL plus GEM and DDP group were significantly smaller than those of either
      rmhTRAIL group or GEM plus DDP group (P < 0.05 and P < 0.01, respectively).
      CONCLUSION: The combination of rmhTRAIL and GEM has a synergistic inhibitory
      effect on human NSCLC cell line NCI-H460 cells either in vitro and in vivo.

PMID- 19173824
TI  - [Sensitivity of two cell lines with acquired resistance to gefitinib to several
      chemotherapeutic drugs].
AB  - OBJECTIVE: To explore the sensitivity of tumor cell lines with acquired
      resistance to gefitinib to several chemotherapeutic drugs and provide preclinical
      basis of available chemotherapy regimens after failure of molecular targeted
      therapy. METHODS: Human lung adenocarcinoma cell lines PC9 and PC9/G with
      acquired resistance to gefitinib were cultured in vitro. The sensitivity to
      chemotherapeutic drugs and inhibition rate of cell proliferation was determined
      by MTT assay. Effects of drugs on apoptosis and expression of P-170 were
      determined by flow cytometry. Difference of gene expression profile between PC9
      and PC9/G cells was analyzed by DNA microarray. Western blot was used to test the
      expression of Akt, phospho-Akt and integrin beta1. RESULTS: The resistance index
      of PC9/G cells to cisplatin was about 5.4-fold compared with that of PC9 cells.
      LY294002 may significantly elevate the sensitivity of PC9/G cells to cisplatin (P
      < 0.05). PC9/G cells were more sensitive to docetaxel than PC9 cells. No
      significant difference of sensitivity to pemetrexed was found between these two
      cell lines. Expression level of P-170 in PC9/G cells was lower than that in PC9
      cells. In PC9/G cells, the expression of integrin beta1 and DNA healing gene was
      high and expression of gene during mitosis was low. The level of expression of
      Akt, phospho-Akt and integrin beta1 in PC9/G cells was higher than that in PC9
      cells. CONCLUSION: In PC9/G cells, a cell line with acquired resistance to
      gefitinib, over-expression of PI3K, integrin and DNA restoration gene and
      continuous activation of PI3K is found to be correlated with resistance to
      cisplatin. Docetaxel or pemetrexed is a more reasonable choice than cisplatin for
      treatment of NSCLC patients who failed to respond to EGFR-TKI.

PMID- 19173825
TI  - [Analysis of the changing trends of frequency and localization of gastric cancers
      arising from different sites of the stomach in population of the high incidence
      area of esophageal and gastric cancers in Hebei province].
AB  - OBJECTIVE: To analyze the changing trends of frequency and localization of
      gastric cancers arising from the gastric cardia, corpus and antrum during the
      past 14 years in population of the high incidence area of esophageal and gastric
      carcinoma in Hebei province, China. METHODS: The clinicopathological data of 4334
      cases of gastric carcinomas among the local residents of Cixian and Zanhuang
      counties, initially diagnosed in our department from 1993 to 2006, were
      retrospectively analyzed. The proportion of gastric carcinomas arising from the
      gastric cardia, corpus and antrum in different years and in patients with
      different sex and ages were analyzed and compared, and the changing trends of the
      frequency of gastric carcinoma arising from different sites of the stomach were
      statistically analyzed. RESULTS: Among all the 4334 gastric carcinomas, gastric
      cardia carcinoma accounted for 68.0%, significantly higher than that of corpus
      (24.2%) and antrum (7.9%; chi(2) = 124.396, P < 0.0001). An increasing tendency
      in the proportion of gastric cardia carcinoma from 1993 to 2006 was seen. The
      percentage of cardiac carcinoma in the high incidence area of esophageal
      carcinoma (Cixian county) was higher than that in the high incidence area of
      gastric cancer (Zanhuang county) (71.2% vs. 51.2%; chi(2) = 109.648, P < 0.0001).
      The increase in the incidence of cardiac carcinoma in Cixian county was mainly
      due to the increase of cardiac carcinoma from 1993 to 2006, while the
      contributing factor for the increase in the proportion of cardiac carcinomas was
      resulted from the decrease of incidence of antrum carcinoma in Zanhuang county
      during the same period. The occurring site of gastric carcinoma was related with
      age of patients (chi(2) = 58.380, P < 0.0001). The percentage of carcinoma of the
      gastric body was highest in < 50 year age group, while that in the gastric cardia
      was highest in 61 - 70 year age group (71.6%). CONCLUSION: The major occurring
      site of gastric carcinoma is the gastric cardia among the local residents in
      population of the high incidence areas of esophageal and gastric carcinomas
      during the past 14 years in Hebei province, China. The increasing trend of
      cardiac carcinoma and decreasing trend of corpus carcinoma in Cixian county and
      antrum carcinoma in Zanhuang county will be maintained in the coming years if the
      epidemiological conditions will not be changed.

PMID- 19173826
TI  - [Expression of ZNRD1 protein in human renal cell carcinoma].
AB  - OBJECTIVE: To investigate the expression of zinc ribbon domain-containing1
      (ZNRD1) in human renal cell carcinoma and normal kidney tissues. METHODS: The
      expression of ZNRD1 protein was examined by immunohistochemical staining in 71
      renal cell carcinomas and 24 samples of normal kidney tissue. The correlation
      between the expressions of ZNRD1 protein and clinicopathologic features was
      analyzed. The expression of ZNRD1 mRNA and ZNRD1 protein was detected by
      quantitative reverse transcriptase-polymerase chain reaction (PT-PCR) and Western
      blot in 20 renal cell carcinomas and corresponding adjacent non-cancerous
      tissues. RESULTS: ZNRD1 protein was detected mostly in the cell nuclei by
      immunohistochemistry. The positive expression rate of ZNRD1 protein was 91.7%
      (22/24) in renal cell carcinomas and 20.8% (5/24) in the normal kidney tissues,
      with a statistically significant difference between cancer and normal kidney
      tissue (P < 0.01). However, no significant correlation was observed between ZNRD1
      protein expression level and clinicopathologic features (P > 0.05). ZNRD1 mRNA
      expression level was significantly higher in renal cell carcinomas (0.6186) than
      that in the normal kidney tissues (0.4273) assessed by RT-PCR (P < 0.01). The
      expression level of ZNRD1 protein by Western blot was 0.5623 in renal cell
      carcinomas, significantly higher than that in normal kidney tissues (0.3885, P <
      0.01). CONCLUSION: ZNRD1 gene and ZNRD1 protein may play an important role in the
      carcinogenesis of renal cell carcinoma. Further investigation is still needed.

PMID- 19173827
TI  - [MR imaging features of different renal cell carcinoma subtypes].
AB  - OBJECTIVE: To compare and analyze the MRI features of different renal cell
      carcinoma (RCC) subtypes. METHODS: The MR images of 81 surgically and
      pathologically confirmed renal cell carcinomas from 79 patients were reviewed
      retrospectively. The MR imaging features of lesions in plain scan, the degree and
      patterns of lesion enhancement (homogeneous, heterogeneous, peripheral), and
      tumor spreading patterns were analyzed. In order to evaluate the diagnostic
      validity of differentiating RCC subtypes using signal enhancement, receiver
      operating characteristic curves (ROC) were generated. The cutoff value of post
      contrast signal intensity to noise ratios (SNR) of the tumor parenchyma were also
      generated in order to differentiate clear cell RCC from other subtypes. RESULTS:
      Of the 81 lesions, 58 were clear cell carcinomas, 10 chromophobe cell carcinomas,
      8 papillary cell carcinomas, and 5 unclassified RCC. All the chromophobe cell
      subtype tumors showed a homogeneous density (P < 0.05). The clear cell subtype
      tumors were likely heterogenous, and also showed heterogenous enhancement with
      mixed signal than other subtypes (P < 0.05). The cutoff value of SNR, which was
      used to differentiate clear cell subtype from the other subtypes, were 616
      (corticomedullary phase), 579 (nephrographic phase) and 278 (excretory phase),
      retrospectively. The nephrographic phase is the most appropriate for
      differentiation, with a sensitivity of 62.1%, specificity of 91.3%, positive
      predictive value of 94.7%, negative predictive value of 48.8% and an accuracy
      value of 70.3%. No significant difference was found in tumor spreading patterns
      among all subtypes of RCC. CONCLUSION: MR imaging features, particularly tumor
      heterogeneity and degree of enhancement are useful in differentiation of the
      renal cell carcinoma subtypes, and in choosing an individualized therapy.

PMID- 19173829
TI  - [Expression of vascular endothelial growth factors (VEGF)-A, -C and -D and their
      prognostic significance and relationship with angio- and lymphangiogenesis in
      gastric cancer].
AB  - OBJECTIVE: To investigate the expressions of vascular endothelial growth factors
      (VEGF)-A, -C and -D and their prognostic significance and relation to angio- and
      lymphangiogenesis in gastric cancer. METHODS: The expression of VEGF-A, -C and -D
      in 123 primary gastric cancers was detected by immunohistochemical staining. The
      lymphatic vessel density (LVD) and microvessel density (MVD) were assessed after
      immunohistochemical double-staining with D2-40 and CD34, respectively. The
      correlation between the expression of those VEGF factors and clinicopathological
      parameters were analyzed by univariate method. The overall survival was evaluated
      by Kaplan-Meier method and log-rank test. Multivariate analysis was carried out
      using Cox proportion hazard model. RESULTS: The positive expression rate of VEGF
      A, -C and -D in primary gastric cancer samples were 64.2%, 65.9% and 41.5%,
      respectively. High expression of VEGF-A, or -C or -D, or any two of them was
      correlated with high LVD (P < 0.05). High expression of both VEGF-A and -C was
      associated with high MVD, lymph node metastasis, LVI and MVI (P < 0.05). Both
      VEGF-C and -D high expression was correlated with LVI and lymph node metastasis
      (P < 0.05). The patients with high expression of these factors had a
      statistically shorter overall survival (P < 0.05). The patients with both VEGF-A
      and -C expression had the shortest survival (56 months). Multivariate analysis
      showed that VEGF-A high expression, MVD, lymph node metastasis and depth of tumor
      invasion were independent survival predictors (P = 0.033, 0.002, 0.019 and P <
      0.001, respectively). CONCLUSION: High expression of both VEGF-A and -C imply
      high potential of lymphangiogenesis, metastasis and poorer survival in gastric
      cancer patients. High expression of VEGF-C and -D may induce lymphangiogenesis
      and promote lymph node metastasis, but only VEGF-A is an independent predictor of
      survival.

PMID- 19173828
TI  - [Aberrant methylation of multiple genes and its clinical implication in
      hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the methylation frequencies of multiple tumor
      suppressor genes (TSGs) in hepatocellular carcinoma (HCC) and the clinical
      implication of aberrant DNA methylation in molecular carcinogenesis of HCC.
      METHODS: Sixty samples of HCC and the paired adjacent liver tissue, 16 samples
      from post-hepatitis cirrhotic livers, 5 from livers with chronic hepatitis and 5
      from normal livers were collected. Eight TSGs frequently silenced by
      hypermethylation of their promoters in various types of digestive tumors were
      selected, including APC, RASSF1A, p16, GSTP1, MGMT, DAPK, SOCS-1 and RIZ1. The
      status of promoter methylation in these 8 genes was investigated using
      methylation-specific polymerase chain reaction. The clinicopathological data of
      HCC were also analyzed in order to evaluate the clinical implication of aberrant
      methylation in HCC. RESULTS: Methylation of the 8 TSGs was quite frequent in HCC,
      with a methylation rate of 95.0% in RASSF1A, 90.0% in APC, 73.3% in GSTP1, 65.0%
      in p16, 61.6% in RIZ1 and 60.0% in MGMT. Methylation of the 6 genes was more
      frequent in HCC than that in adjacent tissues (P < 0.05). The methylation rate of
      MGMT, GSTP1 and RIZ1 in the adjacent tissues was 41.6%, 40.0% and 25.0%,
      respectively, significantly higher than that in cirrhotic liver (P < 0.05). p16
      methylation was more frequently observed in HCC in elderly patients. The
      frequency of MGMT methylation was tended to be higher in giant HCC than that in
      the other types of HCC. Patients with MGMT methylation in the tumor were found to
      have a shorter disease free survival. CONCLUSION: Different frequency of
      methylation in hepatocellular carcinomas, adjacent liver tissues and cirrhotic
      livers implies that epigenetic alteration in the hepatocellular carcinogenesis
      may be a gradually progressive process. Methylation status of MGMT, GSTP1 and
      RIZ1 may be promising in risk assessment of hepatocellular carcinoma and in early
      diagnosis. Furthermore, MGMT methylation might be also used as a potential
      prognostic biomarker for hepatocellular carcinoma patients.

PMID- 19173830
TI  - [Pre- and post-chemotherapy expressions of Th1 and Th2 type cytokines and their
      clinical significance in gastric cancer patients].
AB  - OBJECTIVE: To investigate the pre- and post-chemotherapy expression levels of Th1
      and Th2 type cytokines in peripheral blood CD4(+) T lymphocytes, the changes of
      Th1/Th2 ratio and their clinical significance in patients with gastric cancer.
      METHODS: The levels of specific cytokines in 60 gastric cancer patients were
      detected by flow cytometry before and after chemotherapy with FOLFOX4. RESULTS:
      The level of IFN-gamma from peripheral blood CD4(+) T lymphocytes after
      chemotherapy in the whole group of gastric cancer patients was 11.4% +/- 5.0%,
      significantly higher than that (9.5% +/- 3.4%) before chemotherapy (P < 0.05).
      The level of IL-10 after chemotherapy was 3.6% +/- 1.2%, significantly lower than
      that (4.2% +/- 1.8%) before chemotherapy (P < 0.05). The ratio of Th1/Th2 (IFN
      gamma/IL-4) after chemotherapy was 3.4 +/- 1.0 versus 3.4 +/- 1.6 before
      chemotherapy, without significant difference (P > 0.05). Interestingly, the
      levels of IFN-gamma and TNF-alpha of peripheral blood CD4(+) T lymphocytes in 15
      gastric cancer patients who achieved partial response (PR) after chemotherapy
      were 14.8% +/- 8.0% and 5.9% +/- 2.0%, respectively, both were higher than that
      (6.9% +/- 2.5% and 4.2% +/- 1.3%) before chemotherapy (both P < 0.05).
      Furthermore, the ratio of Th1/Th2 (IFN-gamma/IL-4) after chemotherapy was 4.0 +/-
      1.5, significantly higher than 2.5 +/- 1.2 before chemotherapy (P < 0.01).
      CONCLUSION: Effective chemotherapy may reduce the tumor burden and relieve the
      shift of Th1/Th2 ratio. Improvement in immune function may be a very important
      therapeutic measure due to poor response of chemotherapy in gastric cancer
      patients.

PMID- 19173831
TI  - [Correlation of DPPIV expression with clinicopathological features and prognosis
      in epithelial ovarian carcinoma].
AB  - OBJECTIVE: To investigate the expression of dipeptidyl peptidase IV (DPPIV) in
      patients with epithelial ovarian carcinoma (EOC) and its clinical significance.
      METHODS: Immunohistochemistry (IHC) was used to detect the expression of DPPIV
      protein in 378 formalin-fixed paraffin-embedded EOC tissue samples. The
      expression of DPPIV mRNA in 86 EOC tissue samples were examined by in situ
      hybridization (ISH) using specific FITC-labelled RNA probes. Forty-two samples of
      normal ovarian tissues were used as control. Statistical analyses were carried
      out by Chi-square test, Spearman rank correlation and Kaplan-Meier method.
      RESULTS: Among the 378 epithelial ovarian carcinomas, 351 (92.9%) showed a
      positive expression of DPPIV protein, while only 25/42 (59.5%) of normal ovaries
      had a positive expression by semi-quantitative IHC analysis. The expression level
      of DPPIV protein was significantly lower in the normal ovaries than that in
      ovarian carcinomas (chi(2) = 18.4, P = 0.001). There was no significant
      correlation between the expression of DPPIV protein and age, FIGO stage and
      histological grade (P > 0.05). However, the expression of DPPIV protein was
      significantly associated with histological type (chi(2) = 28.5, P = 0.005). The
      patients with high level expression of DPPIV protein likely had a poor prognosis
      in terms of overall survival (P = 0.02). Of the 86 patients, 84 (97.7%)showed
      positive expression of DPPIV mRNA, also higher than that in normal ovarian
      tissues (P < 0.05). A statistically significant correlation between DPPIV mRNA
      and protein expression was observed (r(s) = 0.66, P = 0.001). CONCLUSION: DPPIV
      may be involved in the carcinogenesis of ovarian cancer, and may become a
      potential prognostic marker for epithelial ovarian carcinoma.

PMID- 19173832
TI  - [The value of endoscopic mucosal resection for dysplasia and early-stage cancer
      of the esophagus and gastric cardia].
AB  - OBJECTIVE: To evaluate the long-term effect and clinical value of endoscopic
      mucosal resection (EMR) with transparent cap for dysplasia and early-stage cancer
      of the esophagus and gastric cardia. METHODS: From September 1996 to June 2007,
      154 lesions in the esophagus or gastric cardia of 147 patients were treated using
      EMR with transparent cap. Among the lesions, there were 69 early-stage squamous
      cell carcinomas in 64 patients and 47 squamous cell precancerous lesions of the
      esophagus in 45 patients, with an average lesion size of (14.8 +/- 6.1) mm
      (range, 3-40 mm), furthermore, there were 23 early-stage adenocarcinomas in 23
      patients and 15 precancerous lesions in the gastric cardia in 15 patients, with
      an average lesion size of (8.2 +/- 4.3) mm (rang, 5-25 mm). All lesions were
      finally confirmed histopathologically. RESULTS: Of the 154 lesions, 139 (90.3%)
      were resected completely through EMR procedure. A close relationship between the
      complete resection rate and the lesion size was observed. The bigger the lesion
      size, the lower the complete resection rate. Endoscopic follow-up was carried out
      in 7 patients for more than 10 years, in 43 for 5 - 10 years, in 31 for 3 - 5
      years and in 66 for less than 3 years. Of 11 dead patients during following-up,
      10 died of other diseases, only 1 of recurrence. The 5-year survival rate was
      96.2% for early-stage esophageal cancer, and 100% for early cancer of the gastric
      cardia. Perioperative complications included oozing bleeding in 5 patients (3.4%)
      and stricture in 1 (0.7%), no perforation occurred in this series. CONCLUSION:
      Endoscopic mucosal resection is suitable to treat precancerous lesions or early
      stage esophageal cancers without invasion into submucosa. Compared with
      conventional resection through open thoracotomy, similar long-term survival and
      curative effect can be achieved by this EMR treatment, preserving a good quality
      of life.

PMID- 19173833
TI  - [Impact of different extents of lymph node dissection on the survival in stage
      III esophageal cancer patients].
AB  - OBJECTIVE: To investigate the safety, feasibility and the impact of different
      extents of lymph node dissection on the survival in the patients with locally
      advanced thoracic esophageal carcinoma. METHODS: From January 2001 to December
      2006, 122 patients with locally advanced thoracic esophageal carcinoma underwent
      radical resection through cervical, thoracic, and abdominal incisions, and were
      randomly divided into two-field lymph node dissection group (Two-FD) and three
      field lymph node dissection group (Three-FD). Life-table method was used to
      compare the difference of survival rates between the two groups. Kaplan-Meier
      method was used to compare the cumulative survival time and median survival time
      between the two groups. Multivariate analysis was performed using Cox model to
      identify the prognostic factors affecting the survival (alpha = 0.05). RESULTS:
      There was no significant difference between the two groups in age, sex, and
      disease stage. Postoperative complication rate and perioperative mortality rate
      were 14.5% and 1.6% in the two-FD group versus 15.0% and 1.7% in the three-FD
      group, statistically without a significant difference (P > 0.05). The 1-, 3- and
      5-year survival rates were 78.2%, 39.6% and 14.5% in the two-FD group, and 83.7%,
      42.4% and 18.1% in the three-FD group, respectively. The median survival time was
      24.0 months in the two-FD group and 31.0 months in the three-FD group. Log-rank
      analysis showed that in the patients without preoperative weight loss, in T3N1M0
      stage, only single regional lymph node metastasis but < 3 in total, the three
      field lymph node dissection achieved a better prognosis (P < 0.05). Multivariate
      analysis using Cox model showed that T and N stages and lymph node dissection
      extent were still risk factors in patients with stage III locally advanced
      thoracic esophageal carcinoma. CONCLUSION: Compared with the two field lymph node
      dissection, the three field lymph node dissection is safe and feasible, and can
      improve the survival for a part of stage III esophageal cancer patients without
      increase in operative mortality and complications.

PMID- 19173834
TI  - [Features of metastasis in different lymph node groups and their significance in
      lymph node dissection in total gastrectomy for gastric cancer].
AB  - OBJECTIVE: To summarize the features of metastasis in different lymph node groups
      (from 1 to 16 groups) in gastric cancer patients treated by total gastrectomy,
      and evaluate their clinical significance in lymph node dissection. METHODS: The
      data of 73 gastric cancer patients with total gastrectomy and lymph node
      dissection from January 2004 to April 2006 were analyzed retrospectively. The
      lymph nodes were divided into 16 groups according to the 13(th) edition of
      gastric cancer treatment guideline of JGCA (The Japan Gastric Cancer
      Association). The metastatic rate and degree of dissected lymph nodes in these
      patients were compared. RESULTS: The metastatic rates of lymph node groups in
      these patients from lower to higher were as follows: group 15, 13/16, 14v, 12,
      10, 9, 11, 8, 2, 6/7, 5, 1, 4, 3. The lowest was the 15(th) group lymph nodes
      (1.4%), the highest was the 3rd group (65.8%), with a statistically significant
      difference between those two groups (P < 0.01). The metastatic degrees of the
      lymph node groups from lower to higher were as follows: 13, 16, 1, 7, 6, 5, 12,
      4, 11, 8, 2, 15, 9, 3, 10, 14v. There was a statistically significant difference
      between the lowest group of lymph node (13(th) group, 10.7%) and the highest
      (14v(th), 56.3%, P < 0.01). CONCLUSION: In the radical total gastrectomy for
      patients with gastric cancer, it is suggested that the regional lymph nodes with
      higher metastatic rate should be resected necessarily, and the group with a
      higher metastatic degree should be dissected completely. If the result of
      sentinel lymph node biopsy in the 3(rd) or 14v(th) group is negative, the
      operation extent can be reduced. If positive, it should be extended. When the
      biopsy result in the 13(th) or 16(th) is positive, palliative operation may be
      indicated. However, if the biopsy result is negative in the 13(th) or 16(th), but
      positive in the 14v(th) group, extended operation is indicated.

PMID- 19173835
TI  - [Clinicopathological features and prognosis of different gastric carcinoid
      subtypes].
AB  - OBJECTIVE: To analyze the clinicopathological features and their relation to
      treatment and prognosis in different gastric carcinoid subtypes. METHODS: The
      data of surgically treated 39 patients with gastric carcinoids (9 of type I and
      30 of type III) were retrospectively analyzed. Univariate and multivariate
      analysis were performed using Chi square test (chi(2)) and Cox model,
      respectively. The survival rates were analyzed by Kaplan-Meier method, and the
      factors affecting survival by Log rank test. RESULTS: Of the 9 patients with type
      I carcinoids, 5 underwent endoscopic or surgical resection, and extra antrectomy
      was performed in 2 patients simultaneously. 3 cases had a proximal gastrectomy,
      and 1 underwent total gastrectomy. Among the 30 patients with type III gastric
      carcinoids, 21 underwent radical resection, 6 had a palliative resection, and the
      remaining 3 underwent exploration and biopsy only due to invasion into adjacent
      organs and distant metastasis. Infiltration beyond the submucosa was found in all
      30 type III gastric carcinoid patients, but in only 1 of 9 patients with type I
      gastric carcinoids. Regional lymph node metastases were found in 27 of 30 type
      III carcinoid cases, but in none of type I. Distant metastases occurred in 5
      patients of type III carcinoid (4 in the liver and 1 in the ovary). There were
      statistically significant differences between type I and type III carcinoids in
      the sex, tumor number, location, size and infiltration depth of the tumors, the
      regional lymph node metastasis, distant metastasis and lymphatic emboli (P < 0.05
      in all). The overall 5-year survival rate was 49.7% for the whole group, and
      100.0% and 37.2% for type I and type III carcinoids, respectively. Univariate
      analysis revealed that the number of tumor, tumor size (> 2 cm), serosal
      invasion, regional lymph node metastasis and distant metastasis were all
      significant factors affecting the survival (P < 0.05 in all). However, by
      multivariate analysis, only distant metastasis was found to be a significant
      prognostic predictor. CONCLUSION: The prognosis of type III carcinoids is much
      poorer than that of type I. Subtyping of gastric carcinoids is helpful in guiding
      clinical management, and also in prediction of malignant potential and prognosis.

PMID- 19173836
TI  - [Factors influencing the long-term survival in pancreatic carcinoma patients
      after radical resection].
AB  - OBJECTIVE: To investigate the factors influencing the long-term survival of
      pancreatic carcinoma patients after radical resection. METHODS: The data of 184
      pancreatic carcinoma patients with radical resection were analyzed
      retrospectively. Analysis of the prognostic factors influencing the long-term
      survival was performed using Cox proportional hazard regression model. RESULTS:
      The overall 1-, 3- and 5-year survival rates in this group were 61.7%, 29.0% and
      14.3%, respectively. They were 78.0%, 38.4% and 25.7%, respectively, for the
      patients with a tumor < 3 cm in diameter, significantly better than those with a
      tumor >or= 3 cm (52.8%, 22.7% and 7.2%, respectively, P < 0.05). Moreover, the 1
      , 3- and 5-year survival rates were 67.6%, 30.5% and 17.4%, respectively, in the
      patients without lymph node involvement, much longer than that in those with
      lymph node metastasis (37.1%, 20.6% and 0, respectively, P < 0.05). Multivariate
      analysis by Cox proportional hazard regression model revealed that the tumor size
      (P < 0.05) and lymph node metastasis (P < 0.01) significantly influenced the long
      term survival of the patients. CONCLUSION: Tumor size and lymph node metastasis
      are significant factors influencing the long-term survival of pancreatic
      carcinoma patients with radical resection. Therefore, early diagnosis and radical
      resection are the key points to improve treatment outcome.

PMID- 19173837
TI  - [Erlotnib in the treatment of advanced non-small cell lung cancer failed to
      previous chemotherapy].
AB  - OBJECTIVE: To investigate the efficacy and side effect of erlotnib for refractory
      patients with advanced non-small cell lung cancer (NSCLC) failed to previous
      chemotherapy. METHODS: Twelve patients with chemo-refractory NSCLC were enrolled
      into this study. Erlotnib was administered at a dose of 150 mg orally once a day
      for a month. The assessment was carried out every month by intensive clinical
      observation and monthly CT scan until disease progression or intolerable toxicity
      occurred. RESULTS: All the 12 patients were evaluable. The response rate
      including complete and partial responses (CR and PR) was 25.0% (3/12). The
      disease control rate including complete, partial response and stable disease (CR,
      PR and NC) was 58.3% (7/12). The clinical benefit rate was 41.7% (5/12). The main
      side effects included skin rash and diarrhea. No patient was withdrawn from the
      treatment due to intolerable toxicities. CONCLUSION: Erlotnib is effective and
      tolerable in the treatment of patients with advanced NSCLC failed to previous
      chemotherapy.

PMID- 19173838
TI  - [Doxorubicin and etoposide-besed combination chemotherapy regimen for peripheral
      T-cell lymphoma].

PMID- 19173839
TI  - [Problems and future direction of preoperative systemic therapy for patients with
      operable breast cancer].

PMID- 19173840
TI  - [Family aggregation of primary hypertension among children and adolescents in
      Beijing].
AB  - OBJECTIVE: To explore the association between histories of hypertension in
      parents and level of blood pressure in their children so as to provide strategy
      for early intervention. METHODS: 19 088 children aged 6-17 years were selected in
      Beijing with stratified random cluster sampling method, and data on influencing
      factors including parental history of hypertension and other related
      environmental factors were collected. Systolic blood pressure (SBP) and diastolic
      blood pressure (DBP) were examined. SPSS 13.0 was used for data analyses.
      RESULTS: The average prevalence of high blood pressure in children and
      adolescents was 9.13% based on the blood pressure criteria Beijing Children and
      Adolescents Metabolic Syndrome (BCAMS) set in 2004. Familial aggregation of
      hypertension in children and adolescents was observed (P < 0.001). There were
      positive associations between the numbers of parents with history of hypertension
      and both SBP and DBP of their offspring. Partial regression coefficients appeared
      to be 0.980 (95% CI: 0.524-1.437) and 0.832 (95% CI: 0. 463-1.201) respectively,
      after controlling for confounding variables including gender, age, residential
      regions, body mass index (BMI), pubertal development, histories of smoking and
      drinking alcohol, fat intakes, physical exercises, parents' education level etc.
      Results from multiple factor logistic regression analysis showed that when
      compared with children whose parents did not have hypertension, the odds ratios
      of children having high blood pressure with only paternal history, only maternal
      history or with both parental histories were 1.688 (1.385-2.059), 1.559 (1.164
      2.087) and 1.273 (0.673-2.406), respectively, after adjustment for confounding
      factors. CONCLUSION: Parental history of hypertension seemed to be an important
      independent risk factor for high blood pressure to their offspring. Heredity
      factors should be emphasized in the development of prevention and intervention on
      hypertension in children and adolescents.

PMID- 19173841
TI  - [Research on the growth references of height, weight and body mass index for
      children under 7 years old].
AB  - OBJECTIVE: To understand the varying features and the trend of length/height-for
      age, weight-for-age and body mass index(BMI)-for-age of children under six years
      old in Ningbo city, Zhejiang province. METHODS: By random clustered sampling, 64
      038 healthy children under six years old in Ningbo were chosen and their
      length/height and weight measured. Means, standard deviation and percentiles of
      length/height-for-age, weight-for-age and BMI were calculated by SAS systems.
      Results of this study were compared with growth standards from WHO 2006 and nine
      urban areas of China, in 2005. RESULTS: Data from our study showed that the
      annual growth rates were basically the same in boys and girls. All these
      indicators increased along with age but the younger the age, the faster the
      growth rate appeared. There were notable differences seen between genders and
      urban-rural distribution. BMIs were also varied with age and sex. BMI reached
      peak between 4 to 6 months, then dropped slowly when age increased. CONCLUSION:
      The means of length/height-for-age, weight-for-age in Ningbo city had exceeded
      the WHO standards, and the growth by year under six year-olds in Ningbo was close
      to the data from nine urban areas of China in 2005.

PMID- 19173843
TI  - [The status on care and nutrition of 774 children staying in rural areas while
      parents were in towns].
AB  - OBJECTIVE: To understand the status on care and nutrition of children living in
      the rural areas (so called 'left-behind' children) while their parents were
      seeking for jobs in the urban areas. METHODS: Cross-sectional study was employed
      in this investigation. The group of 'left-behind' children (n = 774) and the
      comparison group (n = 774) were identified. The ascertainment methods mainly
      included questionnaire, anthropometrics measurements, food-frequency, and
      laboratory examination. RESULTS: Data from this study revealed that the guardians
      of the 'left-behind' children had less ability to ensure daily food that the
      children demanded than the control group and the 'left-behind' children were more
      likely to be poorly attended (chi2 = 6.671, P = 0.036; xhi2 = 15.053, P = 0.001).
      Mothers who chose to work outside of their households would tend to choose bottle
      feeding or decrease the duration of breastfeeding for their infants (chi2 = 5.
      051, P = 0.031; t = -7.201, P = 0.001). The intake of milk and bean products in
      children younger than 2 years old and cereal intake in children aged 2 to 4 in
      the group of 'left-behind' children were obviously lower than that seen in the
      control group (t = -2.150, P = 0.032; t = -2.054, P = 0.040 respectively). The
      'left-behind' children were in high prevalence of anemia, and showed significant
      difference when comparing with the control group (chi2 = 4.560, P = 0.033).
      CONCLUSION: Children under 'left-behind' situation were in poor nutrition.
      Recognition of this situation by the communities, parents and extended families
      would facilitate more attention and effective intervention programs to improve
      the situation.

PMID- 19173845
TI  - [Application of 'waist circumference cutoff point' in screening diabetes mellitus
      among rural residents in mid-western area of Shandong Province, China].
AB  - OBJECTIVE: To determine the value and the optimal cutoff point of waist
      circumference (WC) in screening diabetes mellitus (DM) and to provide evidence
      for DM prevention and identifying population at risk in mid-western rural areas
      of Shandong province. METHODS: A sample consisting 16 341 rural residents was
      selected and studied. All participants were physically examined on height,
      weight, WC and fasting plasma glucose (FPG). Oral glucose tolerance test (OGTT)
      was performed for subjects with FPG valued from 6.1 to 7.0 mmol/L. DM was defined
      according to the criteria set by WHO in 1999. Area under the curve (AUC),
      sensitivity, specificity and Youden index were computed based on the receiver
      operating characteristic (ROC) curve analysis. Optimal cutoff point was
      determined by the maximum of Youden index. RESULTS: The prevalence rates of DM
      for males and females increased along with the rise of WC (trend test chi2 =
      72.01, 122.65, P < 0.01). It appeared significantly higher in those with WC > or
      = 85 cm in females and > or = 80 cm in males, with those WC < 85 cm for females
      and < 80 cm for males, in particular. AUCs were 0.639 and 0.655 for males and
      females respectively and both had significant differences (t = 7.22, 11.07, P <
      0.01). However, the AUCs did not show significant difference (t = 0.70, P > 0.05)
      between males and females. The Youden index reached maximum when WC approached 85
      cm for females (24.90%) and 80 cm for males (24.39%). The sensitivity and
      specificity were 58.04% and 66.86% for males, and 67.08% and 57.31% for females.
      CONCLUSION: WC seemed to be an effective indicator for screening the DM. The
      optimal cutoff point of WC would be 85 cm for females and 80 cm for males in
      screening DM and defining the population at risk in this area.

PMID- 19173846
TI  - [Using repeated measurement of 'analysis of variance' on hypertension patients to
      evaluate the self-management program in the communities].
AB  - OBJECTIVE: To explore the application of repeated measurement 'analysis of
      variance' (ANOVA) in evaluating the effectiveness of 'community-based
      hypertension self-management program'. METHODS: A community-based parallel
      controlled trial was conducted among 3 communities. 169 patients in intervention
      group took part in the course on hypertension self-management program once a week
      and 204 patients in control group received routine hypertension management
      services. Data collected through questionnaire at baseline and 6 months, 12
      months after intervention and were compared through repeated ANOVA measurement.
      RESULTS: Subjects in the intervention group showed statistical significance and
      linear trends in health self-evaluation, distress, in low spirit, self-efficacy
      in managing symptoms (SEMS), self-efficacy to managing diseases in general
      (SEMDG), systolic blood pressure (SBP) and diastolic blood pressure (DBP) over
      time by univariate test of repeated measurement ANOVA. The score of SEMS
      increased from 6.84 +/- 2.53 at baseline to 8.20 +/- 1.44 at 12 months after
      intervention while SEMDG from 7.28 +/- 2.45 to 8.89 +/- 1.05, and SBP decreased
      from 137.66 +/- 7.30 mm Hg (1 mm Hg = 0.133 kPa) to 130.41 +/- 7.71 mm Hg, DBP
      decreased from 84.13 +/- 6.70 mm Hg to 81.04 +/- 5.98 mm Hg respectively. Only
      low spirit and SBP changed over time were seen in the control group. Self
      evaluation, distress,in low spirit, caused by diseases, SEMS, SEMDG and SBP were
      statistically different between control and intervention groups, and the effect
      of interaction between groups and time span were statistically significant on
      indicators as self-evaluation, low spirit, self-efficacy in managing symptoms,
      self-efficacy to manage diseases and SBP etc, by multivariate test of repeated
      measurement ANOVA. CONCLUSION: Repeated measurement ANOVA not only could be used
      to analyze group-effect, but could also explain the effect and the interaction
      among groups and time, to make the results more reliable. The self-management
      approach could improve the health status and self-efficacy of the patients,so as
      to reduce the blood pressure. Our result showed that it was effective for
      hypertensive patients to be on the chronic diseases self-management program.

PMID- 19173847
TI  - [A case-control study on the influencing factors to mild cognitive impairment
      among the community-based elderly population].
AB  - OBJECTIVE: To explore the influencing factors on mild cognitive impairment among
      the community-based elderly population. METHODS: A 'n : m' matched case-control
      study was conducted to analyze the risk factors. Cox regression model of survival
      analysis was selected to deal with non-geometric proportional matched data which
      was difficult to analyze by logistic regression model. RESULTS: Four hundred and
      twenty-three cases together with nine hundred and twenty-five controls were
      interviewed with an uniformed questionnaire. Through univariate and multivariate
      cox regression analysis, the odds ratio and 95% CI of these risk factors appeared
      to be: physical labor as 1.396 (1.092-1.785); smoking as 1.551 (1.021-2.359);
      higher level of blood glucose as 1.354 (1.102-1.664); HDL-C in the serum as 1.543
      (1.232-1.932); LDL-C in the serum as 1.299 (1.060-1.592); lower level of estrogen
      in the serum as 1.263 (1.031-1.547); hypertension as 1.967 (1.438-2.689);
      diabete: 1.381 (1.139-1.675); depressive disorder: 1.406 (1.110-1.780); cerebral
      thrombosis as 1.593 (1.307-1.943); higher SBP as 1.331 (1.129-1.569) and
      ApoEepsilon 4 carrier as 1.462 (1.140-1.873) respectively. Odds ratio and 95% CI
      on protection factors appeared to be: reading newspaper frequently as 0.610
      (0.503-0.740); frequently doing housework as 0.804 (0.665-0.973); frequently
      engaging in social activities as 0.617 (0.502-0.757); reemployment after formal
      retirement as 0.759 (0.636-0.906); having acumen olfaction as 0.900 (0.845
      0.958); having extrovert personality as 0.829 (0.699-0.984); being decisive as
      0.811 (0.662-0.993). CONCLUSION: The major measures to prevent MCI seemed to be
      including the following factors as: being intellectuals, engaging in healthy life
      style and decreasing the risk in developing hypertension, diabetes, depressive
      disorder and cerebrovascular disease. However, olfactory hypoesthesia, cowardice
      and having introvert character, ApoEepsilon 4 carrier etc could be treated as
      early indications to signify MCI.

PMID- 19173848
TI  - [A case-crossover study on air pollutants and the mortality of stroke].
AB  - OBJECTIVE: To investigate the short-term effect of particulate matter in air on
      the mortality of stroke. METHODS: Using time-stratified case-crossover study
      design, an association was examined between stroke mortality and particulate
      matter with aerodynamic diameter of < 10 microm (PM10) of 2002 - 2004 in Hangzhou
      city. Meanwhile, the acute health effect of other gaseous pollutants (sulfur
      dioxide, SO2 and nitrogen dioxide, NO2) was also analyzed. RESULTS: A total of
      9906 deaths of stroke were included. The crude stroke mortality was 83.54 per 100
      000. After being adjusted for meteorological factors, when an increase of 10
      microg/m3 in PM10, SO2 and NO2 in three days was noticed, it appeared that the
      increases of mortality of stroke were 0.56% (95% CI: 0.14%-0.99%), 1.62% (95% CI:
      0.26% - 3.01%) and 2.07% (95% CI: 0.54% - 3.62%) respectively. There was no
      distinct association in multi-pollutant models. In sensitivity analysis, the
      associations were found in all single-pollutant models but not statistically
      significant in multi-pollutant models after replacing the missing values.
      CONCLUSION: It is suggested that the short-term elevation in PM10 as well as SO2
      and NO2 daily concentrations were related to the increase of stroke mortality in
      Hangzhou city.

PMID- 19173850
TI  - [Study on the reliability and validity of the Chinese Menopause Rating Scale
      (CMRS)].
AB  - OBJECTIVE: To evaluate the feasibility, reliability, validity and responsiveness
      of a Chinese Menopause Rating Scale (CMRS). METHODS: Cross-sectional survey and
      convenience sampling were adopted. PARTICIPANTS: women with menopause syndrome
      and those in menopause but without menopause syndrome were recruited. All
      participants were asked to complete the CMRS, Kupperman Index, WHOQOL-BREF and
      MENQOL. The Self-control observation design was adopted when the responsiveness
      was evaluated. Patients were treated with TCM for weeks. MRSTCM was evaluated
      before and after the treatment. RESULTS: (1) Feasibility: 3343 participants
      including 2320 patients and 1023 menopause women, were surveyed in 8 different
      settings. The recovery rate of CMRS was 100%, with a response rate as 99.7%. The
      completion of the CMRS took 10.30 minutes on average. (2)Reliability: Cronbach's
      alpha of CMRS, soma dimension, psychology dimension and community dimension of
      CMRS were 0.93, 0.87, 0.89 and 0.73 respectively, with the correlation
      coefficient of split half of the CMRS. Soma dimension, psychology dimension and
      community dimension were 0.92, 0.89, 0.86 and 0.73 respectively and the test
      retest correlation coefficient of MRSTCM, the soma dimension, psychology
      dimension and community dimension were as 0.88, 0.91, 0.85 and 0.77 respectively.
      (3) VALIDITY: CMRS was established on the basis of connotation of menopause
      syndrome, and a series of steps were adopted to modify the scale. CMRS was
      applicable for patients with menopause syndrome. CMRS seemed to have had good
      content-related validity. The result of exploratory factor analysis was accorded
      with the theory frame of CMRS by and large. The correlations between CMRS and KI,
      CMRS and WHOQOL-BREF, CMRS and MENQOL seemed good. The CMRS was able to
      discriminate between groups of people with or without menopausal syndrome and had
      good discriminative validity. (4) Responsibility: The CMRS was measured based on
      174 patients with menopausal syndrome before and after the TCM therapy. Our
      result showed that the CMRS having the ability to measure the clinically
      important differences. CONCLUSION: CMRS was suitable for outcome assessment of
      menopausal syndrome. This primary research proved that the CMRS had good
      feasibility, reliability, validity as well as responsiveness.

PMID- 19173852
TI  - [Prevalence and risk factors for anxiety among inhabitants in the relief centers
      after the 5 *12 Sichuan earthquake].
AB  - OBJECTIVE: To investigate the prevalence and risk factors for anxiety among
      inhabitants in the relief centers one month after the 5 * 12 Sichuan earthquake
      and to formulate intervention strategies. METHODS: A total of 402 tent
      inhabitants aged > or = 18 years were randomly selected from 13 relief centers of
      4 townships in Jiangyou city. Data were collected by Self-rating Anxiety Scale
      (SAS) and risk factor questionnaires. RESULTS: The prevalence of anxiety among
      inhabitants in the relief centers was 22.1% (95% CI: 18.2%-26.6% ) (89/402). In
      single factor analysis, female, aged > or = 40 years, family per-capita monthly
      income of < 600 Yuan, education level of less than junior high school,
      inconvenient living conditions, history of chronic diseases, limited living space
      in tents, shortage of goods, and sex life being interrupted etc might increase
      anxiety. In multi-factor analysis, female (OR = 2.921), inconvenient living
      conditions (OR = 2.475), history of chronic diseases (OR = 3.997), and limited
      living space in tents (OR = 2.982) were the risk factors for anxiety. CONCLUSION:
      Inhabitants in the relief centers exhibited higher prevalence of anxiety as
      compared with the general population. Measures to improve the living conditions
      of the relief centers, including guarantee of water, electricity and material
      supply, sewage treatment, living space and privacy, and early psychological
      interventions were recommended for prevention and relief of anxiety.

PMID- 19173853
TI  - [The molecular epidemiologic investigation of hantavirus carried by rodent hosts
      in Wenzhou, Zhejiang province].
AB  - OBJECTIVE: To study the epidemiological features of hantavirus in rodents in
      Wenzhou, Zhejiang province. METHODS: Rodents were captured in Wenzhou, where
      hemorrhagic fever with renal syndrome (HFRS) had been endemic. Hantavirus
      antigens in the rat lungs were detected by immunofluorescence assay (IFA).
      Partial S segment (nt 620-999) and partial M segment (nt 2001-2301) sequences
      were amplified by RT-PCR, and then sequenced. Neighbor-joining method was used to
      construct for phylogenetic analysis. RESULTS: A total of 96 rodents were trapped
      in the epidemic areas, and 6 hantavirus antigens were identified from these lung
      samples (6.3%). Partial S and partial M segment sequences were successfully
      recovered from 5 samples and determined. Phylogenetic analysis of these sequences
      indicated that all viruses belonged to Seoul virus (SEOV), regardless of the
      sources (Rattus norvegicus, Rattus tanezumi and Rattus rattoide) that they were
      derived. However, the clustering pattern in the partial S-tree was different from
      that in the partial M-tree, suggesting that the re-assortment between SEOVs had
      occurred. CONCLUSION: All Rattus rats carried SEOV in Wenzhou and the genetic
      reassortment with SEOV had occurred naturally.

PMID- 19173854
TI  - [Analysis on data from the clinical acute viral encephalitis surveillance system
      in three prefectures in Shaanxi during 2005 - 2006].
AB  - OBJECTIVE: To describe the epidemiological features of viral encephalitis and
      burden of Japanese encephalitis (JE), and to identify potential strategies for
      effective JE control measures, using data from the Viral Encephalitis
      Surveillance Program (VESP) launched in Ankang, Baoji, and Weinan prefectures,
      Shaanxi province. METHODS: Data was gathered from sentinel hospitals reporting
      system on all the viral encephalitis (VE) cases identified between June 2005 and
      May 2007. County Center for Disease Control and Prevention (CDC) investigated the
      cases, drawing blood and cerebrospinal fluid (CSF) samples from the hospitals,
      and testing IgM antibody against JE using ELISA. We used Epi Data and Excel for
      data entry and analysis. RESULTS: A total of 1097 VEs were reported and 1053
      (96.0%) had blood or CSF samples collected and tested for IgM antibody against
      JE. Three hundred and eleven cases (29.5%) showed JE antibody positive (JE
      confirmed case). Among the JE confirmed cases, numbers of those under 15 year of
      age accounted for 33.7%, 43.9% and 88.3% in Baoji, Weinan and Ankang prefectures
      respectively. The rest were mainly children aged 5-14 years old (53.3%).
      Toddlers,farmers and children accounted for 85.2% in JE confirmed cases. About
      half of other VE cases (51.0%) were students of all age. Data an investigation on
      398 reported VE cases at discharge, showed that 67.1% of JE confirmed cases
      recovered while 83.7% of the other VE cases fully recovered. The case fatality
      rates were 9.2% for JE confirmed cases and 3.1% for other VE cases. 578 cases
      were followed up at 90-days after discharge, 69.6% of JE confirmed cases and
      90.2% of other VE cases recovered, with case fatality rates were 13.6% and 3.6%
      for JE confirmed cases and for other VE cases, respectively. The sequelae rates
      were 10.0% for JE confirmed cases and 4.5% for other VE cases. CONCLUSION: The
      peak of the VE season was the same as that of JE. There were 45.6% of reported JE
      cases with negative JE IgM, suggesting that it is necessary to carry out
      laboratory testing for clinical diagnosis cases. The fact that high risk
      population was different at prefectures levels suggested that more attention be
      paid in JE control and prevention.

PMID- 19173855
TI  - [Survey on human rabies cases and its viral molecular biological features in
      Baoshan city, Yunnan province].
AB  - OBJECTIVE: To understand the epidemiological features of two rabies cases in
      Baoshan city year 2006 and 2007 and to analyze its source of infection. METHODS:
      Questionnaires were used to do the epidemiological survey on each of the rabies
      cases. Brain tissue samples of rabies patients were collect to detect the rabies
      virus by direct immunofluorescence assay (DFA) and RT-PCR assay. Homology and
      phylogenetic tree were analyzed, based on the whole nucleotide and deduced amino
      acid sequence of P, M and N gene of rabies virus followed by molecular
      epidemiological analysis. RESULTS: In July 2006, one human rabies case was
      identified in Longyang district, and another one in Tengchong county in Baoshan
      city in 2007. The degrees of exposure of these two patients was all at degree
      III. Two brain tissue samples among the dead patients (No. CYN0601H and CYN0701H)
      were confirmed positive by both DFA and RT-PCR assay. The homology analysis of P,
      M and N gene sequences among CYN0601H, CYN0701H and other rabies strains isolated
      from other provinces and other counties, showed that the samples in Baoshan city
      shared the highest homology with the strains in Thailand. Phylogenetic analysis
      indicated that the two samples were very close and all belonged to genetype 1
      Lyssavirus, with the closest relationship between samples in Baoshan city and
      strains in Thailand. CONCLUSION: It was confirmed on the virus molecular level
      that the two patients in Baoshan city were both suffered from rabies. The
      prevalent strains in Baoshan city was probably imported from foreign country,
      suggesting that prevention and control measures on rabies virus in the boarder
      areas of Yunnan should be strengthened.

PMID- 19173856
TI  - [Study on the drug resistance situation among recently infected HIV-1 patients in
      Dehong].
AB  - OBJECTIVE: To study the HIV-1 drug resistance (DR) situation among newly infected
      persons in Dehong. METHODS: 1048 HIV-1 positive blood samples from July to
      December in 2006 from Dehong prefecture of Yunnan, were collected. HIV drug
      resistance were tested using TruGene in newly infected people that were
      distinguished with BED-CEIA, while the subtype were determined with phylogenetic
      analysis using a set of reference sequences available on the Los Alamos Database.
      RESULTS: Of sixty-four successfully analyzed samples, drug resistance mutations
      were detected in 4 samples with the resistance rate as 6.25%. Minor mutation in
      PR region such as M361/V, L63P and H69K appeared frequently and the rates were
      81.25%, 70.31% and 65.63% respectively. The predominantly prevalent strains were
      seen as C/CRF07 _ BC/08 _ BC(65.63%, 42/64) in this study. CONCLUSION: The
      prevalence of genotypic drug resistances in HIV-1 recent infections in Dehong
      prefecture appeared to be at moderate level. Drug-resistance surveillance program
      among HIV-1 infections should be continued and strengthened.

PMID- 19173857
TI  - [Emergence of 16S rRNA methylase gene rmtB in Klebsiella pneumoniae isolates from
      the inpatients in Zhejiang Province, China].
AB  - OBJECTIVE: To investigate the presence and genetic background of 16S rRNA
      methylase gene and Aminoglycoside modifying enzymes (AMEs) genes in Klebsiella
      pneumoniae isolated from the People's Liberation Army 98th Hospital, Huzhou
      district, Zhejiang province, China. METHODS: 25 strains of Klebsiella pneumoniae
      were isolated from the inpatients between September, 2005 and April, 2006. 6
      kinds of 16S rRNA methylase gene (including armA, rmtA, rmtB, rmtC, rmtD and
      npmA), 6 kinds of AMEs genes [including aac (3)-I, aac (3)-II, aac (6')-I, aac
      (6')-II, ant (3")-I and ant (2")-I], intI1, intI2, intI3, mercuric reductase gene
      merA (merA gene were the collective genetic markers of transposons of Tn21 and
      Tn501) and tnpA (tnpA gene were the collective genetic markers of transposons of
      Tn1, Tn2,Tn3 and Tn1000) were analyzed by PCR and verificated by DNA sequencing.
      RESULTS: In 25 strains of Klebsiella pneumoniae, the positive rate of genes of
      rmtB, aac (3)-II, aac (6')-I, ant (3")-I and intI1 were 60.0% (15/25), 4.0%
      (1/25), 48.0% (12/25), 60.0% (15/25) and 96.0% (24/25), respectively. The rest 12
      kinds of genes were all tested negative. The total positive rate of 6 kinds of
      AMEs gene was 84.0% (21/25). CONCLUSION: There were very high positive rate on
      both genes of rmtB and AMEs genotypes in Klebsiella pneumoniae isolated from
      inpatients, and this was the first report of the emergence of 16S rRNA methylase
      gene rmtB in Klebsiella pneumoniae identified in Zhejiang province, China.

PMID- 19173858
TI  - [Sensitivity and specificity of 4 domestic ELISA kits for detection of hepatitis
      B virus markers].
AB  - OBJECTIVE: To compare and analyze the sensitivity, specificity of 4 domestic
      ELISA kits for detection of hepatitis B virus (HBV) markers (HBsAg, anti-HBs,
      HBeAg, anti-HBe, and anti-HBc). METHODS: Five hundred and ninety four serum
      samples collected from patients with chronic hepatitis B and abnormal blood
      donors were detected for HBV markers and by 4 domestic ELISA kits. Samples with
      conflicting results by different diagnostic kits were retested. Samples with the
      HBsAg values close to the cut-off point were detected by Abbott HBsAg
      confirmation kit (Architect HBsAg confirm). Sensitivity of the kits was
      determined, using the national sensitivity reference panels for HBsAg, anti-HBs,
      HBeAg, anti-HBe and anti-HBc. RESULTS: The rates of sensitivity on 4 domestic
      kits for detection of HBsAg were 4 to 10 times lower, and on the 4 domestic kits
      for detection of anti-HBs, HBeAg, anti-HBe and anti-HBc were 4 to 16 times lower,
      as compared to Abbott Architect kits. In addition, the domestic HBV ELISA kits
      had some false positive results. The total coincidence rates of HBsAg, anti-HBs,
      HBeAg, anti-HBe, anti-HBc were 96.46%-98.15%, 94.28%-98.15%, 98.15%-99.49%,
      90.07%-96.30%, 92.09%-96.80%, respectively. CONCLUSION: Both sensitivity and
      specificity of the domestically produced HBV ELISA kits should be improved.

PMID- 19173859
TI  - [Establishment of the standard operation program on multiple loci variable
      numbers tandem repeats analysis typing on Mycobacterium tuberculosis].
AB  - OBJECTIVE: To establish and evaluate the standardized protocol of multiple loci
      variable numbers tandem repeats (VNTR) analysis (MLVA) for genotyping
      Mycobacterium tuberculosis (M. tuberculosis). METHODS: 15 VNTR loci were chosen
      for genotyping 54 Chinese M. tuberculosis strains by PCR-electrophoresis-based
      VNTR analysis and the results were analyzed by software BioNumerics (Version
      5.0). RESULTS: MLVA method was successfully established and standardized,
      including the standard protocol for bacterial culture, DNA isolation,PCR and
      agarose gel electrophoresis and the software analysis. 15 VNTR loci were
      confirmed, including ETRA, ETRB, ETRC, ETRD, ETRE, MIRU10, MIRU16, MIRU23,
      MIRU26, MIRU27, MIRU39, MIRU40, Mtub21, Mtub30 and Mtub39, to be suitable for
      MLVA analysis of M. tuberculosis. CONCLUSION: The standardized MLVA method has
      been established successfully. This method is simple and has powerful capacity
      for genotyping and strain differentiation, can be used for the network
      surveillance on pathogens of M. tuberculosis, and the data are comparable between
      laboratories. It is valuable for tracing the source and studying the trend of
      prevalence during investigation of M. tuberculosis infections.

PMID- 19173861
TI  - [Comparison of five different diagnostic criteria on metabolic syndrome applied
      during physical check-up programs among population aged 35-74, in Taiwan].
AB  - OBJECTIVE: To compare the differences of five diagnostic criteria used for
      metabolic syndrome (MS), issued by International Diabetes Federation (IDF), the
      National Cholesterol Education Program (ATP III), America-Heart-Association
      (AHA), Chinese Medical Association Diabetes Branch (CDS) and The Taiwan Health
      Bureau (TAIWAN), during a physical check-up program among population aged 35-74
      years, in Taiwan. METHODS: A total number of 28 408 people who had received
      physical checkup program first time at the MJ centers, were recruited from 2005
      to 2007. The prevalence of MS and the degree of agreement were both calculated
      according to the five definitions and the results of MS components. Distributions
      and risk factor aggregation of the results were also analyzed. RESULTS: According
      to the five definitions (1) The range of age-adjusted prevalence of MS appeared
      to be 10.6% (CDS) -23.6%(AHA), and were 13.4% (CDS) -27.6% (AHA) and 8.0% (CDS) 
      20.5% (IDF) for men and women respectively. (2) The range of five MS components
      were 22.5% (low-HDL-C) -39.7% (high FPG), with 22.3% of the total subjects
      presented at least 3 risk factors. In addition, 0% (AHA), 6.7% (TAIWAN), 6.9%
      (ATP III), 8.9% (IDF) and 14.9% (CDS) of the subjects diagnosed as MS-free, by
      the five criterions, also appeared of having > or = 3 risk factors. (3) Among all
      the MS subjects, the proportions of clinical symptom complex, having 5, 4 and 3
      MS components were 8.0%, 29.5% and 62.5% respectively. The most common clinical
      symptoms complex of MS were obesity, hypertension and high FPG. (4) The MS
      diagnostic criteria of ATP III, AHA and TAIWAN were in good accordance with Kappa
      index, showing 0.81-0.98 for the three criteria. CDS and IDF were in relatively
      weak agreement when comparing with other definitions with Kappa index showed as
      0.35 and 0.62. CONCLUSION: Our findings revealed big differences in the
      prevalence and aggregation of risk components on MS, when using the five
      definitions. We suggested that prospective cohort studies be planned to
      investigate the impact on cardiovascular disease morbidity and mortality so as to
      verify whites criterion might be suitable to the population in Taiwan,
      considering the possible bias.

PMID- 19173862
TI  - [Study on the relationship between polymorphisms of XPA gene and susceptibility
      of esophageal cancer].
AB  - OBJECTIVE: To explore the relationships between the polymorphisms of xeroderma
      pigmentosum A (XPA) and the susceptibility of esophageal cancer (EC), as well as
      its interaction with environmental factors-gene in Changzhi area, Shanxi
      province. METHODS: A case-control study was conducted, including 196 cases of EC
      and 201 controls. XPA 23G polymorphisms were determined with polymerase chain
      restriction on fragment length polymorphism (PCR-RFLP). RESULTS: The risk of EC
      was significantly degraded in the individuals who had been carrying the XPA
      heterozygote (A/G) and mutation genotype (G/G), compared to those with wild
      genotype (chi2 = 16.21, P < 0.01) and the ORs were 0.58 (0.37-0.91) and 0.32
      (0.18-0.56), respectively. There was negative interaction between XPA 23G
      mutation genotype and the consumption of pickled food (S = 0.04, API= -0.77).
      CONCLUSION: Genetic polymorphism in the XPA 23G might be associated with
      esophageal cancer in Changzhi area, and there was a negative action between XPA
      predisposing genotype and the consumption of pickled food.

PMID- 19173863
TI  - [Study on the interaction under logistic regression modeling].
AB  - When study on epidemiological causation is carried out, logistic regression has
      been commonly used to estimate the independent effects of risk factors, as well
      as to examine possible interactions among individual risk factor by adding one or
      more product terms to the regression model. In logistic or Cox's regression
      model, the regression coefficient of the product term estimates the interaction
      on a multiplicative scale while statistical significance indicates the departure
      from multiplicativity. Rothman argues that when biologic interaction is examined,
      we need to focus on interaction as departure from additivity rather than
      departure from multiplicativity. He presents three indices to measure interaction
      on an additive scale or departure from additivity, using logarithmic models such
      as logistic or Cox's regression model. In this paper, we use data from a case
      control study of female lung cancer in Hong Kong to calculate the regression
      coefficients and covariance matrix of logistic model in SPSS. We then introduce
      an Excel spreadsheet set up by Tomas Andersson to calculate the indices of
      interaction on an additive scale and the corresponding confidence intervals. The
      results can be used as reference by epidemiologists to assess the biologic
      interaction between factors. The proposed method is convenient and the Excel
      spreadsheet is available online for free.

PMID- 19173871
TI  - [Changes of waist circumference distribution and the prevalence of abdominal
      adiposity among Chinese adults from 1993 to 2006].
AB  - OBJECTIVE: To describe the changes of waist circumference distribution and the
      prevalence of abdominal adiposity on Chinese adults aged 20-65, from 1993 to
      2006. METHODS: This paper was based on the data collected in the China Health and
      Nutrition Survey in 1993, 1997, 2000, 2004 and 2006, and the subjects were men
      and women from 20 to 65 years old. Using the LMS method to construct the 15th,
      50th, and 85th percentile waist circumference percentile curves. The recommended
      cut-off points for abdominal adiposity were 85 cm and above for males and 80 cm
      and above for females, suggested in the "Guidelines for Overweight and Obesity
      Prevention and Control for Chinese Adults" in defining abdominal adiposity.
      RESULTS: Compared with 1993, the 2006 waist circumference distribution curves
      flattened and expanded at higher levels in males and females. The waist
      circumference increased from 77.1 cm to 82.9 cm among males and from 75.8 cm to
      78.9 cm among females. A gradient of increasing prevalence of abdominal obesity
      was also observed in both sexes. In males, the prevalence increased from 17.9% to
      42.5% while in females, it increased from 28.8% to 46.9%. Similar trends of
      increasing waist circumference and abdominal obesity were observed in
      underweight, normal weight, overweight and obesity. Subjects defined by body mass
      index (BMI) suggesting that primary prevention of abdominal obesity should be
      viewed as one of the major public health problems in China. CONCLUSION: This
      study indicated that the rapid increase in waist circumference among Chinese
      adults from 1993 to 2006. A gradient of increasing prevalence of abdominal
      obesity was also observed in males and females. Unless measures are taken to slow
      the increase in the course of the abdominal adiposity epidemic, the burden of
      obesity associated morbidity and mortality in the Chinese can be expected to
      increase in future years.

PMID- 19173872
TI  - [Estimation on the mortality and disease burden attributed to selected risk
      factors in Shandong province].
AB  - OBJECTIVE: To determine the major health related risk factors and provide
      evidence for policy-making, using health burden analysis on selected factors
      among general population from Shandong province. METHODS: Based on data derived
      from the Third Death of Cause Sampling Survey in Shandong, years of life lost
      (YLLs), years lived with disability (YLDs) and disability-adjusted life years
      (DALYs) were calculated according to the GBD methodology. Deaths and DALYs
      attributed to the selected risk factors were than estimated together with the PAF
      data from GBD 2001 study. The indirect method was employed to estimate the YLDs.
      RESULTS: 51.09% of the total deaths and 31.83% of the total DALYs from the
      Shandong population were resulted from the 19 selected risk factors. High blood
      pressure, smoking, low fruit and vegetable intake, alcohol consumption, indoor
      smoke from solid fuels, high cholesterol, urban air pollution, physical
      inactivity, overweight and obesity and unsafe injections in health care settings
      were identified as the top 10 risk factors for mortality which together caused
      50.21% of the total deaths. Alcohol use, smoking, high blood pressure, low fruit
      and vegetable intake, indoor smoke from solid fuels, overweight and obesity, high
      cholesterol, physical inactivity, urban air pollution and iron-deficiency anemia
      were proved as the top 10 risk factors related to disease burden and were
      responsible for 29.04% of the total DALYs. CONCLUSION: Alcohol use, smoking and
      high blood pressure were determined as the major risk factors which influencing
      the health of residents in Shandong. The mortality and burden of disease could be
      reduced significantly if these major factors were effectively under control.

PMID- 19173873
TI  - [Study on food preference and dietary behavior to overweight/obesity in school
      children and adolescents in Guangzhou: a case-control study].
AB  - OBJECTIVE: This study assessed the effect of food preference and dietary
      behaviors on the risk of overweight or obesity in school children and adolescents
      aged 6 - 19 years. METHODS: All overweight or obese students, with age- and
      school-matched controls were recruited for this case-control study from 28
      elementary and secondary schools in Guangzhou urban districts from October 2006
      to April 2007. Weight and height were measured, and body mass index was
      calculated for the classification of obesity, overweight and underweight. Their
      food preference and behaviors were assessed using a structured questionnaire
      completed by their parents. Behavior and food preference were classified into
      four levels, and the relevant bottom levels were defined as control groups.
      Logistic regression was used to assess independent determinants of overweight and
      obesity. RESULTS: Among 7136 participants, 1947 cases and 2136 normal weight
      controls from 5755 students with valid questionnaire data were included in the
      study. Results from univariate analysis showed that odds ratios for overweight or
      obesity were 0.60-0.69 in those with most preference (top group) on vegetables,
      fruits, candy, evening snacks, 0.50 in the students of less food partiality,
      1.84, 1.30 and 1.26 in those of most preference for pork, beef and deep-fried
      foods, and 5.14 in students with fastest speed during eating, respectively (all P
      < 0.05). Vegetable intake, evening snacks preference, speed during eating and
      food partiality remained with significant association with overweight and obesity
      in multivariate analysis after adjusted for age, sex, family socio-economical
      status and their parents' body build. The adjusted odds ratios (OR) and 95%
      confidence intervals (95%CI) of the above items became 0.55 (0.42 - 0.73), 0.48
      (0.35 - 0.65), 0.50 (0.39 - 0.65), and 4.32 (3.23 - 5.80) as compared to the
      relevant lowest categories, respectively. CONCLUSION: Behaviors as eating more
      vegetables and slow-eating might be protective factors against overweight and
      obesity in school children.

PMID- 19173874
TI  - [Prevalence and risk factors of prehypertensive status in people from the rural
      area of Lanxi county, Heilongjiang province].
AB  - OBJECTIVE: To access the prevalence of prehypertensive stage and its associated
      risk factors in rural inhabitants from Lanxi county in Heilongjiang province.
      METHODS: Through cluster multistage and random sampling methods, local people
      aged > or = 15 years old in Lanxi county were selected. A survey on blood
      pressure and associated risk factors was carried out. Overnight fasting blood
      specimen of people aged > or = 35 years old was collected. Chi-square test, t
      test and logistic regression analyses were then performed. RESULTS: 5272
      residents were surveyed including 2539 male and 2733 female subjects. The overall
      prevalence of prehypertension was 36.34%. The prevalence of prehypertension
      appeared to be higher in males (39.50%) than in females (33.41%) (chi2 = 58.9887,
      P < 0.0001). The prevalence of prehypertension decreased with increasing age in
      men > or = 25 years old (chi2 = 96.0698, P < 0.0001), and in women > or = 35
      years old (chi2 = 11.5784, P = 0.0208). Data from multivariable logistic
      regression showed that being male, aged (> or = 55 years old), with waist
      circumference as > or = 85 cm for men and > or = 80 cm for women, BMI > or = 25.0
      kg/m2 and fasting plasma glucose > or = 7.0 mmol/L were risk factors of
      prehypertension while high-density lipoprotein cholesterol < 0.9 mmol/L was shown
      as a protective factor (OR = 0.740, P = 0.0036). Dose-response relationships were
      seen between prehypertension and age, BMI and FPG. CONCLUSION: Prehypertension
      was popular in the rural area, with high prevalence seen in teenagers. Programs
      on prehypertension prevention should start from teenagers. Risk factors of
      prehypertension increased when people became age 55 or older. There was a need to
      monitor BP more often and to control BP through non-drug methods.

PMID- 19173875
TI  - [Study on the relationship between obesity and clustering of major risk factors
      on cardiovascular diseases in the elderly].
AB  - OBJECTIVE: To study the correlation between obesity and clustering of major risk
      factors on cardiovascular disease in the elderly. METHODS: A cross-sectional
      study was conducted. Data from 546 elderly aged 60-90 were analyzed for the
      relationship between obesity and clustering of risk factors for cardiovascular
      diseases, with descriptive statistical methods, chi2 test, logistic regression
      and ROC curve. RESULTS: (1) The positive rates of the four major risk factors and
      clustering appeared an upward trend along with the BMI and/or the WC. The overall
      positive rate of clustering of risk factors among the total 546 elderly people
      was 59.5%, and 52.5% in males, 65.7% in females. (2) As compared with females,
      males had a higher growth rate of clustering with the elevating of BMI and WC,
      and odds ratios of the highest-level groups were 13.579 and 2.876 in males and
      females, respectively. (3) Both BMI and WC were independent influencing factors
      for male (P < 0.05), and logistic regression coefficients were 0.196 and 0.074
      for BMI and WC, respectively. Only WC appeared to be the independent influencing
      factor for females (P < 0.05), while BMI was not (P = 0.537), with logistic
      regression coefficient as 0.060 for WC. (4) The combination equation of male's
      BMI and WC was CE(BMI + WC) = 0.726 x BMI + 0.274 x WC, with the optimum cut-off
      value as 41.59, and the sensitivity and the specificity were 0.785 and 0.598,
      respectively. CONCLUSION: Four major risk factors for cardiovascular diseases
      were often related to obesity while control of BMI and WC were of great
      significance to the primary prevention of cardiovascular disease. The combined
      equation of BMI and WC could be used to predict the risk of clustering.

PMID- 19173876
TI  - [Study on the activity of serum bone alkaline phosphatase and its relations to
      the heritability among pre-puberty twins].
AB  - OBJECTIVE: To evaluate calcium deficiency and demand in pre-puberty twins and to
      analyze the heritability of serum bone alkaline phosphatase (BALP). METHODS: A
      total of 73 pairs of twins aged 9-16 years were examined by BALP test.
      Microsatellite polymorphism was used to diagnose the zygosity of twins, while
      both intraclass correlation coefficient method and Christian formula were
      performed to investigate heritability of serum BALP. RESULTS: The results of
      zygosity diagnosis displayed that 34 pairs of twins were monozygotic (MZ) twins
      and 39 pairs were dizygotic (DZ) twins. 97.9% of the subjects appeared unusual in
      the activity of BALP, with activity of BALP > 250 U/L in 43.1% of subjects and
      200-250 U/L in 54.8% of the subjects. The intake of calcium was unsatisfied in
      48.4% of the boys and 39.0% in girls. Less than 10.0% of the subjects were
      satisfied with the intake of calcium in each age group while over 45.0% of the
      subjects in 10-13 age group were deficient in calcium. Differences between the
      means of BALP in different sex groups (t = 1.633, P = 0.105) and different age
      groups (F = 0.323, P = 0.924) were not statistically significant. Heritability
      analysis displayed that intra-class variation, inter-class variation, intra-class
      correlation coefficient were 191.54, 1462.22, 0.77 in MZ twins, and those were
      491.03, 1475.57, 0.50 in DZ twins respectively with the heritability of BALP
      activity as 0.54. CONCLUSION: Calcium deficiency is commonplace in pre-puberty
      twins. Our data showed that the BALP activity was influenced both by genetic
      (54%) and environmental (46%) factors.

PMID- 19173877
TI  - [Analysis on the risk factors of maternal weight for fetal macrosomia].
AB  - OBJECTIVE: To investigate the relationship between maternal weight gain and the
      increasing speed of weight in different pregnant terms and macrosomia. In order
      to reasonably manage pregnancy and decrease the morbidity of macrosomia. METHODS:
      106 newborns whose birth weights were equal to or greater than 4000 g were
      specified as macrosomia, while 106 newborn with birth weights lying in 2500 -
      3999 g were under the control group. A case-control study was conducted to
      compare the corresponding factors such as maternal BMI, weight before pregnancy
      and the change of weight during pregnancy respectively. RESULTS: Indicated by
      both simple and multiple unconditional logistic regression analysis, the cause of
      fetal macrosomia was mainly associated with the factors including the maternal
      weight before pregnancy (OR = 2.204, 95%CI: 1.377 - 3.529), maternal weight gain
      in 12-pregnant weeks (kg per week) (OR = 1.961, 95%CI: 1.204 - 3.194), maternal
      weight gain in 20-gestation weeks (kg per week) (OR = 1.811, 95%CI: 1.078 -
      3.041), maternal weight gain in 30-pregnant weeks (kg per week) (OR = 1.858,
      95%CI: 1.095 - 3.153) and virile newborn (OR = 2.630, 95%CI: 1.420 - 4.850. When
      in 30-pregnant weeks, the pregnant women with 0.5 - 1.0 kg weight gain per week
      had 1.13 fold risks comparing to those whose weight gains were less than 0.5 kg
      per week. CONCLUSION: Maternal weight before pregnancy, weight gain during
      pregnancy and fetal sex appeared a closer relation to macrosomia. It is necessary
      to monitor the change of maternal weight during different pregnancy periods,
      especially for the 30th-pregnant weeks.

PMID- 19173878
TI  - [Pretest survey on the Chinese menopause rating scale].
AB  - OBJECTIVE: To select the items from the Chinese menopause rating scale (CMRS)
      through pre-testing those people with menopausal syndromes. METHODS: 293 people
      were surveyed in Guangzhou in 2005, among which 196 people with menopausal
      syndromes and others without. Psychometrics methods were employed to develop the
      scale. The item pools were all round. Methods used would include: focus group
      discussion and interviews, subjective evaluation method and Delphi method, to
      preliminarily screen the items. Data on scales measured from 196 cases with and
      97 subjects without menopausal syndromes during the menopausal period, were
      collected. Again, seven statistical methods were employed to select the items.
      RESULTS: The 40-items scale for menopausal syndrome was formed to include: a)
      three domains: somatic (18-items), psychological (14-items) and social (5-items);
      b) one general appraisal item; c) two lie-test items. CONCLUSION: The Chinese
      menopausal syndrome scale we used seemed to possess good content validity,
      feasibility and intra-class reliability.

PMID- 19173879
TI  - [Current situation on the treatment modules of diarrhea cases in 12
      counties/cities of Guangdong, Henan and Gansu provinces in China].
AB  - OBJECTIVE: To understand the situation of diarrhea cases treatment modules in the
      areas and to provide reference data for setting up national strategies for
      treatment and control of diarrhea diseases. METHODS: Using the method of
      multistage and cluster random sampling, we selected twelve counties/cities and 60
      streets communities/villages from Guangdong, Henan and Gansu provinces that
      representing three kinds of economic development. According to the definition of
      diarrhea case published by World Health Organization, we conducted a four-time
      investigation at the community level in four different seasons. RESULTS: The
      overall incidence of diarrhea within two weeks was 0.79% (95%CI: 0.74% - 0.84%)
      in the residents from twelve counties/districts in Guangdong, Henan and Gansu.
      The incidence rate within two weeks under the 5 years old was 2.30% (95%CI: 1.96%
      - 2.67%), obviously higher than the incidence rates seen in other age groups. The
      average percentage of visiting a doctor seeking for help on diarrhea within the
      two weeks was 55.89% for the three provinces. The highest percentage was 79.88%
      in the age group under 5 years old. 35.38% of the patients with diarrhea in urban
      area went to the community or street clinics for treatment, but 75.04% of the
      diarrhea cases in rural areas went to see village or private rural doctors.
      Factors influencing the behaviors of visiting a doctor seeking for help were
      found by logistic Regression method. It was found that factors as: when diarrhea
      cases with voluminous or soft-rice like watery stools or with dark blood stools;
      when a patient was with fever, more episodes per day or with longer duration, the
      patients would turn more to the doctors for help. Diarrhea cases from the rural
      areas would see doctors more often than the cases from the urban areas. People
      having had partial 'new rural medical insurance' would see doctors more often
      than those without medical insurance. CONCLUSION: We studied the modules of
      diarrhea case treatment between the urban and rural area in Guangdong, Henan and
      Gansu provinces and found that the percentages of visiting a doctor for diarrhea
      treatment in the rural areas was higher than that in the urban areas. Both
      residents at all age and under 5 years old, the percentage of visiting a doctor
      for diarrhea treatment showed a sharp increase in the last two decades.

PMID- 19173880
TI  - [Human immunodeficiency virus/sexually transmitted infection, risk behavior and
      sexual networks among men who have sex with men in Taizhou city, Zhejiang
      province].
AB  - OBJECTIVE: To study the prevalence of human immunodeficiency virus (HIV),
      sexually transmitted infection (STI), risk behavior and the sexual networks among
      men who have sex with men (MSM) in Taizhou city, Zhejiang province. METHODS: A
      cross-sectional study was applied with venue-based sampling in 2 MSM gathering
      sites in Taizhou. 'Informed Consent' principle was applied and MSM were studied
      through a structured questionnaire. Blood samples were collected from those who
      accepted free and confidential HIV/STI counseling and then tested for HIV,
      syphilis, HCV and HSV-2 antibodies with ELISA. HIV positive sera were certified
      with western blot. RESULTS: 106 MSM were investigated and 97 qualified
      questionnaires were collected. 25.0% (23/92) of these MSM have ever had 1 female
      sex partner while 47.8% (44/92) had 2 or more. 14.3% (13/91) of them reported
      having had 1 male partner who had engaged in anal sex and 80.2% (73/91) had 2 or
      more. 22.1% (19/86) of them had participated in group sex but 62.5% (55/88) of
      them did not always use condom when having anal intercourse. 15.1% (14/93) of
      them had 1 oral sex partner while 75.3% (70/93) having 2 or more. 38.9% (37/95)
      of them had sex with female sex worker, and 35.5% (33/93) had sex with male-to
      male sex worker. 15.3% (13/85) of them had once been male-to-male sex worker
      themselves. 3.9% (3/77) of them were found HIV positive in blood tests, with
      24.7% (18/73) positive of syphilis, 15.1% (11/73) positive of HSV-2 but HCV
      appeared to be negative. 46 cases reported their egocentric recognition networks,
      with mean degree of 5.91 (ranging 0 - 10), and mean density of 0.548 (ranging
      0.000 - 1.000). 43 sexual networks were identified, with mean degree of 2.70
      (ranging 0 - 10), and mean density of 0.246 (ranging 0.000 - 1.000). CONCLUSION:
      Risk behaviors, such as multiple sex partners, low proportion of condom use and
      commercial sex engagement, both with heterosexuals and homosexuals, were
      extensively existed among MSM in Taizhou, and the prevalence of HIV/STI was
      relatively high. Their sexual networks seemed complicated but there might be in
      place of some substantially isolated MSM groups with high risk of HIV/STI
      infection. More study should be applied to identify the relationship between
      sexual networks and HIV/STI transmission.

PMID- 19173881
TI  - [Risk factors on road traffic accidents in middle school students: a matched case
      control study].
AB  - OBJECTIVE: To investigate the predictors of road traffic accidents (RTAs) in
      middle school students, a case-control study was designed to seek new clues for
      prevention and control on RTAs in this population. METHODS: Cases were 116
      students who experienced RTAs from 2005/01/01 to 2005/12/31. 116 students were
      served as controls who were from the same class of the cases and matched by age
      and sex. Information on personal behavior, family conditions, and knowledge,
      attitude, practice (KAB) on road traffic of these children were collected and
      compared. Conditional logistic regressions were conducted to analyze the
      relationship between these factors and RTAs. RESULTS: Compared to the controls,
      the cases showed more negative attitude and risk-taking-behaviors especially in
      riding bicycle. However, knowledge on road safety showed less significant
      differences between case and control groups. The negative attitude and risk
      taking-behaviors were independent risk factors for RTAs by logistic regression.
      In addition, distance from home to school that longer than 1000 m seemed a risk
      factors for RTAs, while high education levels among mothers was a protective
      factor. CONCLUSION: Road safety attitude and behavior, distance from home to
      school were the main influence factors for RTAs among middle school students. It
      seemed more important in improving the attitude and behavior on road safety than
      to enhance the knowledge for prevention and control of RTAs among middle school
      students.

PMID- 19173882
TI  - [Analysis on economic efficacy regarding previous strategies and current
      recommendations for vaccination against hepatitis B virus in China].
AB  - OBJECTIVE: To evaluate the outcome of hepatitis B vaccination strategies
      performed over the past 14 years and different alternatives recommended for
      future immunization programs from the point of view of economic efficacy.
      METHODS: Methods used would include: process of decision analysis including
      building the tree; populating the model with parameters; estimating expected cost
      benefit and effectiveness and deterministic and probabilistic sensitivity and
      threshold analysis. RESULTS: In China, over the past 14 years from 1992 to 2005,
      around 5.348 billion Chinese Yuan were provided for hepatitis B vaccination but
      the total benefits were 272.825 billion Yuan, with net benefits as 267.477
      billion Yuan. The cost for each infection averted was 81.99 Yuan while the
      benefit of one Yuan being invested had 51.01 Yuan in return. For the future
      recommendations, data from the study revealed that the priority of hepatitis B
      vaccination for newborns and vaccinations plus passive immunization of newborns
      of HBsAg positive mothers were most effective approaches. If the other population
      as adolescents was included into the vaccination program, then screening for
      hepatitis B virus markers before accepting the vaccination appeared to be one of
      the most cost-saving strategies. Sensitivity and threshold analyses showed that
      hepatitis B virus marker was the most important factor, followed by the cost of
      vaccine, vaccination coverage and vaccine efficacy, in order. CONCLUSION: Routine
      vaccination of infants in successive birth cohorts to prevent HBV transmission
      was a cost-effective strategy administrated over the past 14 years in China. In
      the following years, the immunization of newborns was still the preferential
      strategy from a societal perspective. However, vaccination provided to other
      population including adolescents seemed economically less attractive.

PMID- 19173884
TI  - [Viral surveillance on rabies in Hunan province, in 2006].
AB  - OBJECTIVE: To understand the source and distribution of rabies virus (RV) in
      Hunan province with viral surveillance in order to provide scientific measures
      for prevention and control on rabies. METHODS: Brain samples from healthy-looking
      domestic dogs were collected in the agricultural markets at the districts of
      high, middle, and low incidence rates and detected by direct Immunofluorescence
      assay (DFA). Positive samples would be further detected by RT-PCR and the
      surveillance samples were detected by RT-PCR. The positive samples detected by RT
      PCR were sequenced with N gene. RESULTS: The infection rate of those healthy
      looking domestic dogs with rabies virus was 2.78% in Hunan province in 2005. 23
      positive samples' N gene were sequenced and their similarities were 88.8% -
      100.0%. The results indicated that Hunan rabies virus N gene aberrance was mainly
      synonymous aberrance and did not carry obvious regional characteristics. The
      rabies virus were circulating among different districts in Hunan province, and
      the neighboring provinces such as Guizhou, Hubei, Guangxi, Jiangsu and Henan.
      There were no positive samples detected in salivary, blood and urine samples.
      There was one positive sample detected in two skin samples. CONCLUSION: There are
      dogs infected with rabies virus found in Hunan province and this study showed
      that rabies virus detected in Hunan had a close genetic relationship with those
      rabies identified in other provinces, suggesting that study on the immunity and
      management of dog related rabies should be strengthened.

PMID- 19173887
TI  - [Epidemiological characteristics and the strategy of vaccination on hemorrhagic
      fever with renal syndrome in the last 10 years, in China].
AB  - OBJECTIVE: To study the epidemiological characteristics and vaccination strategy
      of hemorrhagic fever with renal syndrome (HFRS) in China, from 1998 to 2007.
      METHODS: National data on the prevalence of HFRS during 1998 to 2007 were
      collected and analyzed. Spatial, time and population distributions of HFRS cases
      were described. RESULTS: HFRS appeared to remain endemic in the country, while
      the majority of cases (accounting for 81.76% of total cases), were located in
      Shandong, Heilongjiang, Liaoning, Hebei, Shaanxi, Hunan, Jilin and Zhejiang
      provinces. The occurrence of HFRS appeared to be seasonal, with two peaks in
      spring season and autumn/winter season, with 10.00% of the cases occurred in
      these peak months. The incidence rates were at a relatively low level because of
      the continuous decline of HFRS in the recent years. With age distribution, 0.97%
      were younger than 10, 96.71% were between 10 and 70, 87.32% were between 15 and
      60, and 2.31% were older than 70. The proportion of male patients accounted for
      three quarters. Around 70.00% of the cases were farmers. Young and middle-aged
      male farmers were at high risk. CONCLUSION: The descriptive study on
      epidemiological characteristics of HFRS in the recent years had provided
      scientific evidence for vaccination strategy, suggesting the key regions, sub
      populations as well as types of vaccines be determined.

PMID- 19173885
TI  - [Study on the public health emergent events in Fujian province in 2004--2007].
AB  - OBJECTIVE: To study the public health emergent events (PHEE) in Fujian province,
      from 2004 to 2007. METHODS: Descriptive and analytic methods were used to analyze
      the PHEE in Fujian province according to the internet-based surveillance reports.
      RESULTS: From 2004 to 2007, there were 304 emergency events being surveyed. Of
      all the events, there were 7 (2.30%) belonged to serious-degree of grade II,
      57(18.75%) to grade III and 240 (78.95%) to grade IV, but with no grade I.
      Results showed that the attack rate in affected population was 25.82 per
      thousand, the mortality rate was 0.08 per thousand and the fatality rate was
      0.32%. The numbers of emergency events decreased 2.82% on average, each year. A
      total number of 169 (55.60%) events occurred in schools with 71 (23.36%) in the
      countryside. Numbers due to infectious disease-born was 233 (76.64%) including
      avian flu, cholera and dengue fever were predominant pathogens of the grade II
      and grade III emergency events. 57 (18.75%) of the events was due to food
      poisoning. The epi-garph showed that there were two peaks. i.e. in Mar-Apr and
      Sep, contributed 43.1% to the total number of events. CONCLUSION: Emergency
      events showed a stable decrease in Fujian province with communicable disease and
      food poisoning the two major sources and more commonly seen in schools and
      countryside. We suggest that the government and community pay more attention to
      the emergency events of avian flu, cholera and dengue fever.

PMID- 19173888
TI  - [Study on integrons in Escherichia coli which producing extended-spectrum beta
      lactamases, isolated from stool specimen of chicken].
AB  - OBJECTIVE: To analysis the dissemination of integrons in the extended-spectrum
      beta-lactamases (ESBLs) producing Escherichia coli, isolated from stool specimen
      of chicken and to study the relations between the resistance and the integrons of
      these isolates. METHODS: The Escherichia coli isolates were collected from Gansu,
      Hubei, Sichuan provinces and Beijing municipal city, and were isolated from stool
      specimen of chickens. Using WHONET software, the Escherichia coli producing ESBLs
      were selected, and then detected by PCR method class 1, 2, 3, 4 integrase. PCR
      products of the variable region of the integron were sequenced. RESULTS: 54 of
      the 224 (24.1%) isolates were ESBLs producing Escherichia coli. Class 1 integron
      were detected in 63.0% of the isolates, and aadA1, aadA2, aadA5, aadA22, dfrA12,
      dfrA17, dfrI, aar-3 were found in the variable region and aadA gene encodes
      resistant to streptomycin, spectinomycin, dfr gene to trimethoprim and aar to
      rifampicin. We realized that aadA22 was the first time detected in China. Class 2
      integron were detected in 5.6% of the isolates, Class 3 integron was detected in
      3 isolates. CONCLUSION: Class 1 integron was the most commonly seen integron in
      Escherichia coli, encoding the resistance to streptomycin, spectinomycin and
      trimethoprim. Integrons were contributed to the horizontal transfer of resistant
      genes in the same or different species, suggesting that the antimicrobial
      resistance and the dissemination of integrons should be monitored.

PMID- 19173889
TI  - [Sequence analysis for Hexon genes of types 3, 7 and 11 of adenoviruses
      identified in Beijing].
AB  - OBJECTIVE: The objective of this study was to develop a rapid, sensitive and
      specific method for identifying and typing for adenovirus from clinical specimens
      and to learn about the viruses identified in Beijing on the molecular bases.
      METHODS: Primers were designed using hexon gene of adenovirus as target. One
      primer pair was designed as universal primers for amplifying a 1278 bp gene
      fragment located at the hexon gene of adenovirus types 3, 7, 11 and 21. Four
      primer pairs located within the region of this 1278 bp fragment were designed
      specifically for amplifying adenoviruses types 3, 7, 11 and 21, which were used
      for a multiplex nest-PCR in a single tube. The products from this multiplex nest
      PCR were 502 bp (for type 3), 311 bp (for type 7), 880 bp (for type 11) and 237
      bp (for type 21), respectively. The type of the adenovirus being tested could be
      determined after agarose electrophoresis analysis of the PCR products. Sequencing
      was performed for part of the Hexon genes at the 5' end from types 3, 7 and 11
      strains isolated from clinical specimens and the sequences were compared with
      corresponding genes published in GenBank. RESULTS: PCR products with predicted
      sizes were visualized in the agarose gel for prototype strains of adenovirus
      types 3, 7, 11 and 21, but not for other respiratory viruses, indicating that the
      technique is specific for typing without cross reaction with other viruses. Out
      of 61 clinical specimens which had been proved to be adenovirus positive by
      tissue culture and/or immunofluorescence assay, 37 were found as adenovirus type
      3 (37/61, 60.73%), 17 as adenovirus type 7 (17/61, 27.9%), 3 was adenovirus type
      11 (3/61, 4.9%). 1 was positive for both type 3 and 7 (1/61, 1.6%), suggesting
      that the patient was co-infected with type 3 and 7 adenoviruses. No adenovirus
      type 21 was detected. Out of the 61 positive specimens, three showed positive on
      both tissue culture and immunofluorescence but could not be identified under the
      methods we used, suggesting that these 3 strains (4.9%) were with the types other
      than types 3, 7, 11 and 21. Data from sequence analysis indicated that
      adenoviruses types of 3, 7 and 11 in this study shared high homology with
      corresponding types of the strains published in GenBank. Three of the type 3
      adenovirus in this study shared highest homology with the adenovirus type 3
      identified in Guangzhou, China in 2005. Three of the type 7 adenovirus shared
      highest homology with the adenovirus type 7 identified in Japan in 1998 and 3 of
      type 11 adenovirus shared highest homology with the adenovirus type 11 identified
      in Japan in 2004. Comparing with types 3 and 7, the type 11 in this study showed
      highest diversity with the corresponding type in GenBank, indicated by the
      dispersing of the varied amino acids within the region of HVR1 and HVR7 of the
      Hexon genes. CONCLUSION: This multiplex nest-PCR method had the advantages of
      rapid, sensitive and specific and could be used for identifying types of
      adenoviruses in clinical specimens. Although adenovirus types 3, 7 and 11 from
      Beijing strains shared high homology with the corresponding genes in GenBank,
      some variances were noticed, especially in type 11 strains.

PMID- 19173890
TI  - [The impact of complication on quality of life among diabetic patients in urban
      China].
AB  - OBJECTIVE: To explore the impact of chronic complications of type 2 diabetic
      mellitus (T2DM) on quality of life (QOL) among T2DM outpatients in urban China.
      METHODS: A cross-sectional study was carried out in 1524 T2DM outpatients
      recruited from 15 hospitals in 4 major cities of China. Questionnaire interviews
      were used to collect data on general characters and complications of T2DM. SF-36
      questionnaire (version 1) was used and self-completed by patients under the help
      from interviewers for those having difficulties in reading. T test, one-way ANOVA
      and generalized linear model were used to explore the association between
      complications of T2DM and quality of life. RESULTS: Complication was a
      significant predictor leading to poorer SF-36 subscale scores (decreased by 4.68 
      16.06 scores) and two summary scores (PCS, MCS). The scores of role-physical
      subscale (decreased by 22.45%) and role-emotional subscale (decreased by 16.28%)
      decreased much more than the other subscales in patients with complication.
      Overall, QOL was reduced by 11.02% in patients with complication. The QOL had a
      gradual decrease with the increasing number of complications. The average scores
      descended from 2.82 to 10.33 in the eight subscales with the increase of one
      complication. CONCLUSION: Having complication or multiple complications seemed to
      be predictors of poor QOL among T2DM outpatients.

PMID- 19173891
TI  - [Prevalence and incidence of deep venous thrombosis among patients in medical
      intensive care unit].
AB  - OBJECTIVE: A cross-sectional study was carried out to observe the prevalence,
      incidence and risk factors of deep venous thrombosis (DVT) in patients from
      intensive care unit (ICU). METHODS: Patients who were admitted to respiratory
      intensive care unit (RICU) and emergency intensive care unit (EICU) of Beijing
      Chaoyang Hospital and Beijing Anzhen Hospital were screened in our study. All
      patients enrolled underwent compression ultrasonography (CUS) within 48 h upon
      their admission to the ICUs. CUS was re-performed at 10 - 14 day, or when leaving
      ICU or at the time patients developed signs and symptoms (pain, heat, redness,
      edema) of DVT. Risk factors which were presumed associated with DVT were
      recorded. The main identified outcome was the presence of DVT. The secondary
      outcome was pulmonary thromboembolism (PTE). RESULTS: DVT was found in 30
      patients of 252 patients within 48 h (11.90%). One hundred seventy-two patients
      were performed CUS two times or more. 26 patients (15.12%) had DVT. D-dimer,
      history of operation, kidney failure appeared to be independent risk factors for
      DVT in ICU patients. 13 patients were suspected PTE and 3 patients diagnosed as
      PTE. CONCLUSION: ICU doctors should pay more attention to DVT, which is
      relatively common in ICU patients.

PMID- 19173892
TI  - [The application of artificial neural network in studying landless farmer's
      mental health problems].
AB  - To introduce a method of classification with high precision--the artificial
      neural network (ANN), and to compare the results using logistic regression
      method. Using data from 1070 landless peasants' mental health survey, the
      artificial neural network models and logistic regression model were built and
      compared on their advantages and disadvantages of the two models. The prediction
      accuracy for artificial neural network was 94.229% and for logistic regression it
      was 51.028%. ANN appeared to have had good ability on generalization. ANN
      displayed advantages when conditions of classical statistical techniques could
      not be met or the predictive effect appeared to be unsatisfactory. Hence, ANN
      would make a better fracture of its application in medical research.

PMID- 19173893
TI  - [Progress on the study of Chikungunya disease].

PMID- 19173894
TI  - [Study on molecular epidemiology of Puumala-like virus].

PMID- 19173895
TI  - [Epidemic investigation of prevalence of stroke and vascular dementia among Uygur
      and Han nationalities (> or = 50 years) in Xinjiang].

PMID- 19173896
TI  - [Evaluation on typing of the mycobacterial interspersed repetitive units as a
      practical approach in gene-typing of the Beijing family].

PMID- 19173897
TI  - [Investigation of measles outbreak in Chaoyang district of Beijing].

PMID- 19173898
TI  - [Comparison of immunity to measles between floating and local population].

PMID- 19173899
TI  - [Investigation on behavior-influencing factors of 226 addicts of voluntary
      detoxification].

PMID- 19173900
TI  - [Purification and observation of inactivated hemorrhagic fever with renal
      syndrome vaccine in human].

PMID- 19173901
TI  - [Molecular classification of breast cancers].

PMID- 19173902
TI  - [Interaction between an insertion/deletion polymorphism in pepsinogen C and
      Helicobacter pylori infection in the development of gastric cancer].
AB  - OBJECTIVE: This study was designed to investigate the interaction between
      pepsinogen C(PGC) insertion/deletion polymorphism and Helicobacter pylori(Hp)
      infection, together with its different subtype strains, in the development of
      gastric cancer (GC). METHODS: PGC Genotypes were determined by polymerase chain
      reaction (PCR) assay in 564 subjects with superficial gastritis (NOR), gastric
      ulcer (GU), atrophic gastritis (AG) and GC, who were frequency-matched as 1:1.
      Serum Hp-IgG antibodies were determined by an enzyme linked immunoadsorbent assay
      (ELISA). Hp genetic subtypes in 171 patients with Hp infection were determined by
      PCR methods. RESULTS: In GU, AG and GC, the OR of interaction was 8.69 (P =
      0.049), 11.16 (P = 0.02), and 10.61 (P = 0.03), respectively; the interaction
      index of PGC homozygous allele 1 genotype and Hp infection was 5.40, 6.48 or
      4.34, respectively; the attributable proportions were 0.721, 0.770 and 0.697,
      respectively. In AG and GC, no significant interactions were observed between PGC
      polymorphism and Hp genetic subtypes. CONCLUSION: The findings of this study
      suggest that PGC insertion/deletion polymorphism and Hp infection seem to present
      a positive interaction in the development of gastric cancer. While no
      interactions may be present between PGC polymorphism and Hp genetic subtypes.

PMID- 19173903
TI  - [Mda-7-carrying replication-defective adenovirus selectively kills hepatocellular
      carcinoma cells by facilitating release of proapoptotic protein from
      mitochondria].
AB  - OBJECTIVE: To investigate the mechanism that mda-7/IL-24 selectively kills
      hepatocellular carcinoma (HCC) HepG2 cells in vitro. METHODS: HCC cell line HepG2
      and normal liver cell line L02 were infected with Ad.mda-7. The expression of mda
      7/IL-24 was detected by RT-PCR and ELISA, respectively. The apoptotic effects
      were confirmed by Hoechst staining and flow cytometry assay, respectively.
      Furthermore, Bcl-2 family proteins, cytochrome C, Smac/DIABLO and caspase-9 were
      determined by Western blot. RESULTS: The exogenous mda-7/IL-24 gene was expressed
      in HepG2 and L02 cells infected with Ad.mda-7. Ad.mda-7 induced apoptosis in
      HepG2 but not in L02 cells in vitro. The induction of tumor cell apoptosis is
      correlated with the increasing expression of Bax and decreasing expression of Bcl
      2 and Bcl-xL genes, then facilitated the releasing of cytochrome C and
      Smac/DIABLO from mitochondria to cytoplasm and increasing the expression of
      caspase-9, eventually, resulted in apoptosis. CONCLUSION: Ad.mda-7 selectively
      induces growth inhibition and apoptosis in hepatocellular carcinoma HepG2 cells
      but not in normal L02 hepatocytes in vitro, and the mechanism might involve the
      decrease of Bcl-2 and Bcl-xL and increase of Bak expression, facilitating the
      release of cytochrome C and Smac/DIABLO from mitochondria in HCC cells.

PMID- 19173904
TI  - [Mechanism of enhancement of the CTL activity in mice co-expressing CD80, CD86
      and CD137L genes].
AB  - OBJECTIVE: To study the mechanism of enhancement of the CTL activity in mice co
      expressing of CD80, CD86 and CD137L genes. METHODS: The mice were randomly
      divided into five groups, named A, B, C, D and E. The group A and B were control
      groups (CG). H22-BAL B/c HCC mouse model was established by subcutaneous
      injection with hepatocellular carcinoma cells of cell line H22-Wt (group A), H22
      neo (group B), H22-CD80/CD86(+) (group C), H22-CD137L(+) (group D) and H22
      CD80/CD86/CD137L(+) (group E), respectively. On the 14th, 35th, 56th and 84th day
      after the first inoculation of tumor cells, TUNEL staining and DNA ladder
      examination were used to detect apoptosis of splenic T lymphocytes in all groups
      at each post-inoculation time point. Electrophoretic mobility-shift assay (EMSA)
      method was used to detect the activity of nuclear factor kappaB (NF-kappaB) in
      splenic T lymphocytes in each group at each time point post-inoculation. RESULTS:
      Apoptosis was found in a great number of T lymphocytes in CG on the 14th day,
      much more than that in group C and E. The number of apoptotic T cells in group C
      had a significant difference compared with that in the group E from 14th to 84th
      day (P = 0.003). DNA ladder analysis showed typical positive results in group C
      and E. The significant apoptosis fragments were found in group C on 21st, 35th
      and 84th days. NF-kappaB activity of T cells in groups C and E was remarkably
      higher than that of groups CG and D, with higher in group D than that of CG (P =
      0.002), and with no significant difference between group C and E on 14th day. The
      activity in group E was stable and remarkably higher than that of group C on 56th
      and 84th days after the first inoculation. CONCLUSION: H22-CD80/CD86/CD137L(+)
      induces higher NF-kappaB activity of the host T cells by synergistic action of
      CD28 and CD137, which may be one of the mechanisms of enhancement of the host CTL
      activity induced by co-expression of CD80, CD86 and CD137L genes.

PMID- 19173905
TI  - [Changes of expression and sequence of ERCC1 in cadmium chloride-induced
      transformed 16HBE cells at different stages].
AB  - OBJECTIVE: To explore the expression and sequence of ERCC1 gene in CdCl2-induced
      transformed human bronchial epithelial 16HBE cells at different stages. METHODS:
      Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemcial
      staining (SP method) were used to measure the ERCC1 mRNA and protein expression
      in 16HBE cells at different passages treated with CdCl2 (the 5th, 15th, 35th
      passage, and neoplastic cells from tumors formed in nude mice). ERCC1 exon 3,exon
      4 of the 16HBE cells and tumor cells from nude mice were amplified by polymerase
      chain reactions (PCR), the amplified DNA strips were purified,and the exons were
      detected by DNA analysis. RESULTS: During the passages of 16HBE cells treated
      with CdCl2, the expression of ERCC1 gene was decreased gradually. The ERCC1 gene
      mRNA and protein expression levels of the CdCl2-transformed 35th passage 16HBE
      cells and tumor cells from nude mice were significantly decreased comparing with
      those in non-transformed 16HBE cells (P < 0.01). In the CdCl2-induced tumorigenic
      cells in nude mice, there was adenine (A) deletion in 1st site of ERCC1 exon 4.
      The mutation was frame shift mutation. CONCLUSION: The decreased expression and
      mutation of ERCC1 gene may be the possible carcinogenic mechanism of CdCl2.

PMID- 19173906
TI  - [Ultrastructural analysis of glioma stem cells-progenitors].
AB  - OBJECTIVE: It is well known that glioma stem cells-progenitors (GSCP) proliferate
      indefinitely and hardly differentiate in vitro, however, the reasons remain
      unknown. The aim of this study was to explore the ultrastructural basis of GSCP.
      METHODS: GSCP, kept by our laboratory, were collected, embedded, and cut into
      ultrathin sections and observed under the transmission electron microscope.
      RESULTS: A single GSCP usually had relatively well developed mitochondria, Golgi
      apparatuses, ribosomes, and undeveloped rough endoplasmic reticulum, but seldom
      lysosomes and no typical autophagosomes were found, and the nuclear-cytoplasmic
      ratio was high. The nuclei frequently contained huge amounts of euchromatin and a
      small quantity of heterochromatin, and in most nuclei there were only one
      nucleolus, however, two or more nucleoli were also common. Typical apoptotic
      cells could hardly be found in tumor-spheres, and between neighboring cells in
      tumor-spheres there were incompletely developed desmosomes or intermediate
      junction. CONCLUSION: The ultrastructural features of glioma stem cells
      progenitors showed that BTSCP were very primitive and the lack of autophagy and
      the underdevelopment of some other cellular organelles are probably the reasons
      for the differential inhibition of GSCPs.

PMID- 19173907
TI  - [Correlation of Helicobacter pylori infection with the expression of COX-2 and
      EGFR and VEGF in human gastric carcinoma].
AB  - OBJECTIVE: To investigate the correlation of Helicobactor pylori (Hp) infection
      with the expression of COX-2, EGFR and VEGF in human gastric carcinoma. METHODS:
      The expression of COX-2, EGFR and VEGF was detected by immunohistochemistry in
      samples of 61 gastric cancers and 20 cancer-adjacent tissues. Western blotting
      was performed in samples of 10 gastric cancers and corresponding cancer-adjacent
      tissues. Hp infection was detected in 47 patients by fast urea enzyme test and
      (13)C breath test. RESULTS: The results of immunohistochemistry showed that the
      positive expressions of COX-2, EGFR and VEGF in gastric carcinoma were 59.02%,
      36.07% and 60.66%, respectively, significantly higher than that in the normal
      mucosa (25.00%, 0 and 30.00%, respectively). There was a positive correlation
      between the expression of COX-2, EGFR and VEGF and gastric carcinoma. The
      expression of COX-2 and EGFR was 75.76% and 45.45% in the gastric carcinomas with
      Hp infection, significantly higher than that in those without (28.57% and
      14.29%). The protein expression of COX-2, EGFR and VEGF detected by Western blot
      in gastric carcinomas was also significantly higher than that in normal mucosa.
      CONCLUSION: COX-2, EGFR and VEGF are overexpressed in gastric carcinoma, and
      there is a positive correlation among them. Hp infection may upregulate the
      expression of COX-2 and EGFR in gastric cancer tissues.

PMID- 19173908
TI  - [Establishment and evaluation of a prognostic prediction model for patients after
      complete resection of non-small cell lung cancer and multidisciplinary therapy].
AB  - OBJECTIVE: A bias may be produced when only TNM stage is used to predict the
      prognosis of non-small cell lung cancer (NSCLC) after complete resection and
      multidisciplinary treatment. The reason is that histological type,
      differentiation, and postoperative treatment which may also affect the survival
      are excluded in the prognosis prediction. The aim of this study is to establish
      and evaluate a prognostic prediction model for NSCLC patients based on
      pathological parameters after completely resection and postoperative treatment.
      METHODS: According to the theory of Nottingham index model, a prognostic
      prediction model was established based on the pathological parameters and
      postoperative management of 899 NSCLC patients after complete resection and
      multidisplinary treatment in our hospital from Jan.1, 1997 to April, 2001, and
      its efficiency and feasibility were evaluated. RESULTS: Univariate analysis and
      multivariate analysis showed that histological type (H), T stage (T), N stage
      (N), M stage (M), and postoperative mediastinal radiotherapy for positive lymph
      node (R) were independent factors affecting the survival of NSCLC after complete
      resection and multidisciplinary treatment. The prognostic prediction model based
      on these parameters is: S = 0.338H + 0.178T + 0.549N + 0.647M-0.361R. The high
      and low risks of prognostic index (PI) were 1.6695 and 1.1160, respectively. The
      5-year survival rates of the patients in the low, middle and high risk groups
      stratified by this model were 70.1%, 54.5%, and 22.5%, respectively, with a
      significant difference among the groups (chi(2) = 132.091, P = 0.000).
      CONCLUSION: A model based on the pathological parameters and postoperative
      management has been established, which may be helpful in predicting the prognosis
      for NSCLC after complete resection and multidisciplinary management.

PMID- 19173909
TI  - [Relationship of dose-volume histogram parameters and computed tomography grading
      of radiation-induced lung injury in patients with non-small cell lung cancer
      treated by three-dimensional conformal radiotherapy].
AB  - OBJECTIVE: To explore the relationship of dose-volume histogram (DVH) parameters
      and computed tomography grading of radiation-induced lung injury in patients with
      non-small cell lung cancer (NSCLC) treated by three-dimensional conformal
      radiotherapy (3D-CRT). METHODS: One hundred sixty-nine patients with stage I
      approximately III NSCLC, treated by 3D-CRT and followed by CT scan for more than
      six months after 3D-CRT, were divided into grade 0 to grade 4 based on the
      appearance of radiation-induced lung injury on CT image defined jointly by
      radiotherapist and radiologist. The patients were divided into CT positive group
      (grade 2 to grade 4) and CT negative group (grade 0 to grade 1), then the
      treatment planning shown to the patients were reviewed to compare and analyze the
      relationship of CT grading of radiation-induced lung injury and the DVH parameter
      selected. RESULTS: Regardless of whole lung or tumor-bearing lung, there was a
      statistically significant difference in normal tissue complication probability
      (NTCP) between the patients grouped with different CT grading of radiation
      induced lung injury, and the mean of NTCP increased along with upgrade of CT
      grading. There was a statistically significant difference of mean lung dose (MLD)
      regardless of whole lung or tumor-bearing lung between the patients grouped with
      different CT grading of radiation-induced lung injury, and MLD increased along
      with upgrade of CT grading. There was a statistically significant difference of
      the volume received equal or more than 20 Gy (V(20)), 30 Gy (V(30)), 40 Gy
      (V(40)) of whole lung and tumor-bearing lung between the patients grouped with
      different CT grading of radiation-induced lung injury, and V(20), V(30), V(40)
      increased along with upgrade of CT grading. There were not statistically
      significant differences of the DVH parameters of the contralateral lung in the
      patients of different groups based on the CT grading. On statistical analysis,
      the DVH parameters of whole lung and tumor-bearing lung closely correlated with
      CT grading of radiation-induced injury of the tumor-bearing lung, and there was a
      relatively strongest relationship between NTCP and CT grading of the tumor
      bearing lung (eta = 0.522). CONCLUSION: DVH parameters such NTCP, MLD, V(20),
      V(30), and V(40) are statistically correlated closely with CT grading of
      radiation-induced lung injury after radiotherapy for the patients with NSCLC
      treated by 3D-CRT. Therefore the parameters can be selected as the reference for
      evaluation after 3D-CRT for patients with NSCLC.

PMID- 19173910
TI  - [Prospective evaluation of the clinical significance of ultrasonography, helical
      computed tomography, magnetic resonance imaging and endoscopic ultrasonography in
      the assessment of vascular invasion and lymph node metastasis of pancreatic
      carcinoma].
AB  - OBJECTIVE: To evaluate prospectively the efficacy of ultrasonography (US),
      helical computed tomography (HCT), endoscopic ultrasonography (EUS) and magnetic
      resonance imaging (MRI) in the assessment of vascular invasion and lymph node
      metastasis in pancreatic carcinoma. METHODS: Consecutive 68 patients with
      pancreatic carcinoma were studied. Results of each imaging techniques regarding
      vascular invasion and lymph node metastasis were compared with the surgical and
      pathological findings. RESULTS: (1) US findings were confirmed moderately in
      accordance with surgical and pathological results in the evaluation of inferior
      cava vein, splenic artery and vein invasion of pancreatic carcinoma. HCT findings
      of evaluating superior mesenteric vein, portal vein, splenic vein were confirmed
      greatly in accordance with surgical and pathological results. The results of
      evaluating superior mesenteric artery, inferior cava vein, splenic artery, common
      hepatic artery, proper hepatic artery, celiac trunk, abdominal aorta were
      confirmed moderately in accordance with surgical and pathological results. MRI
      findings of evaluating superior mesenteric artery and vein, portal artery and
      vein were moderately in accordance with surgical and pathological results. EUS
      findings of evaluating splenic vein were confirmed greatly in accordance with
      surgical and pathological results, and moderately in accordance with surgical and
      pathological results in the evaluation of superior mesenteric vein. (2) EUS had
      the highest sensitivity (75.0%), accuracy (87.5%), and negative predictive values
      (91.7%) in the evaluation of lymph node metastasis. The sensitivity of HCT and
      MRI were 37.5% and 35.3%, which were significantly lower than that of EUS. The
      sensitivity of US was 18.7%, which was the lowest of all. In addition, the
      multivariate logistic regression analysis confirmed that EUS had an independent
      predictive value (OR: 34.50, 95%CI: 6.54 - 182.09). CONCLUSION: Helical CT should
      be considered the most precise technique to evaluate vascular invasion. EUS had
      an independent predictive value with respect to tumor metastasis to regional
      lymph nodes.

PMID- 19173911
TI  - [Analysis of factors influencing recurrence and metastasis following curative
      resection of pancreatic ductal adenocarcinoma].
AB  - OBJECTIVE: To investigate the factors influencing recurrence and metastasis
      following curative resection of pancreatic ductal adenocarcinoma and analyze the
      prognosis. METHODS: The clinicopathological and follow-up data of 56 patients who
      underwent curative resection for pancreatic ductal adenocarcinoma between Jan.
      1997 and Dec. 2006 in this hospital were analyzed retrospectively. RESULTS: The
      recurrence rate after curative resection was 73.2% (41/56). The recurrence rate
      after operation at the time of 3 months, half year, 1 year and 2 years was 26.8%
      (15/56), 51.8% (29/56), 64.3% (36/56) and 69.6% (39/56), respectively. Hepatic
      metastasis and local recurrence accounted for 36.6% and 31.7% of the cases,
      respectively. The 3-year accumulated survival of this group was 22.7%. The
      symptom presenting time, back pain, preoperative level of CA19-9, tumor size,
      AJCC stage and T stage were correlated with metastasis/recurrence. Univariate
      analysis revealed that the preoperative level of CA19-9, T stage and the tumor
      size were prognostic factors. Cox regression analysis revealed that only tumor
      size was an independent prognostic factor. CONCLUSION: The metastasis or
      recurrence mostly occurs within 2 years after curative resection, and the liver
      is the most common site of metastasis. High recurrence rate is the major reason
      causing the failure of curative resection and short survival time after
      operation. The symptom presenting time, back pain, preoperative level of CA19-9,
      tumor size, AJCC stage and T stage are correlated with metastasis/recurrence. The
      tumor size is an independent prognostic factor.

PMID- 19173912
TI  - [Synchronous primary cancers of the endometrium and ovary: review of 43 cases].
AB  - OBJECTIVE: To investigate the clinical and pathological characteristics,
      treatment methods, and prognosis of synchronous primary cancers of the
      endometrium and ovary. METHODS: The clinical data of 43 patients with synchronous
      primary cancers of the endometrium and ovary were retrospectively reviewed. The
      survival was calculated by Kaplan-Meier method and compared using the log-rank
      test. RESULTS: The median age at diagnosis was 49 years (range, 28-73 years). The
      most common symptoms were abnormal vaginal bleeding (69.8%) and abdominal or
      pelvic pain (44.2%).Pelvic masses were found in 39.5% of the patients and
      enlarged corpus in 27.9% at physical examination, while pelvic masses were found
      in 67.4% of the 43 patients (29 cases) and thickening or abnormal endometrium in
      23.3% (10 cases) during ultrasound examination. Of 25 patients examined by
      CT/MRI, pelvic masses were found in 13 cases and enlarged uterus in 11 cases. All
      15 patients who underwent endometrial biopsies were proven to have endometrial
      carcinomas. Serum CA125 level was found to be elevated in 22 of the 34 examined
      cases (64.7%) with a median value of 500 U/ml (range, 39-3439 U/ml). FIGO stages
      of endometrial carcinomas: IA 18 cases, IB 20 cases, IC 2 cases, IIA 3 cases;
      Stages of ovarian carcinomas: IA 19 cases, IB 4 cases, IC 7 cases, II 4 cases,
      III C 9 cases. Twenty-four patients (55.8%) were in stage I both endometrial and
      ovarian carcinomas. Thirty-one patients underwent total hysterectomy plus
      bilateral salpingo-oophorectomy with omentectomy and appendectomy, meanwhile, 12
      patients had pelvic lymph node dissection. Thirty-eight of the 43 patients
      (88.4%) had a pathologically proven endometrial adenocarcinoma. The predominant
      ovarian histology was endometrioid or mixed tumor with endometrioid components
      (30/43, 69.8%). Postoperatively, 26 patients (60.5%) received adjuvant
      chemotherapy alone, 12 had chemotherapy plus radiotherapy, only one patient had
      radiation alone and the remaining 4 cases received no adjuvant treatment. The 3-
      and 5-year survival rates of the group were 87.4% and 71.1%, respectively. The 3-
      and 5-year survival rates of patients with both endometrioid and ovarian
      carcinomas were higher than that of those with non-endometrioid or mixed subtypes
      (93.8%, 82.0% vs. 79.7%, 69.0%). The 3-year and 5-year survival rates of patients
      with early stage disease were better than those of the other patients (93.3%,
      93.3% vs. 69.7%, 36.7%). Recurrence developed in 15 patients (34.9%). It was
      showed by univariate analysis that lower CA125 level, early FIGO stage, and
      adjuvant chemotherapy plus radiotherapy significantly and positively affect the 5
      year survival rates, while only early FIGO stage and chemotherapy plus
      radiotherapy were revealed by multivariate analysis as independent prognostic
      factors. CONCLUSION: Synchronous primary cancers of the endometrium and ovary are
      different from either primary endometrial carcinoma or ovarian cancer, while it
      can usually be detected in early stage and with a good prognosis. The impact of
      the CA125 level on prognosis needs to be further studied. Surgical treatment
      alone may be enough for early stage patients. Chemotherapy plus radiotherapy may
      be necessary for advanced stage patients.

PMID- 19173913
TI  - [Evaluation of whole body MRI and diffusion-weighted MRI in detecting intranodal
      lesions in patients with lymphoma].
AB  - OBJECTIVE: To evaluate the whole body MRI and diffusion-weighted MRI in detecting
      intranodal lesions in patients with lymphoma. METHODS: Whole body MRI and
      diffusion-weighted MRI (DWI) were performed in 23 patients with histologically
      proven lymphoma. A conventional coronal MRI scan from head to inguinal groove was
      done for whole body scanning. In the DWI, axial MRI scans were performed after
      segmentation based on SENSE technique, and all images were merged into whole body
      image reconstruction by software. RESULTS: 417 lymph nodes were detected by MRI
      in the 23 patients. The overall positive rate of whole body MRI and DWI was 79.1%
      and 89.7%, respectively. It was 70.9% versus 85.2% and 79.4% versus 90.1% for the
      lymph nodes of < 2 cm and 2-3 cm in diameter, with a significant difference
      between the two methods (P < 0.01). However, it was 94.7% versus 97.9% for the
      lymph nodes of > 3 cm in diameter, not significantly different between the two
      methods (P > 0.05). Both methods had similar sensitivity in detecting the lymph
      nodes in the neck, supraclavicular and infraclavicular fossae, mediastinum and
      axillary fossa. However, the positive rate of whole body MRI was 51.2%, 43.8% and
      52.2%, significantly less sensitive than 83.7%, 71.9% and 87.0%, respectively, by
      DWI in detecting the lymph nodes in the retroperitoneal space, pelvic cavity and
      inguinal groove (all P < 0.01). CONCLUSION: Both whole body MRI and diffusion
      weighted MRI have a relative high sensitivity in detecting intranodal lesions for
      patients with lymphoma, showing a certain value in clinical application.

PMID- 19173915
TI  - [(18)F-FDG PET-CT in detecting the primary tumor in patients with metastatic
      cancers of unknown primary origin].
AB  - OBJECTIVE: To evaluate the value of (18)F-FDG PET-CT in detecting the primary
      tumor in patients with metastatic cancers of unknown primary origin. METHODS:
      Sixty-seven patients with metastatic cancers of unknown primary origin after
      extensive conventional diagnostic work-up were enrolled into this study. (18)F
      FDG PET-CT scans were performed at approximately 60 minutes after the intravenous
      injection of 7.4 MBq (18)F-FDG/kg, then delayed imaging scans was done at
      approximately 180 minutes for detecting the primary focus. The standardized
      uptake value (SUV) >or= 2.5 on standard PET/CT imaging was considered as
      positive. Ten percent increase of retention index (RI) was also regarded as
      positive. The correlation between (18)F-FDG PET-CT results and histopathological
      and clinical findings were analyzed, and the SUV of detected primary focus and
      that of metastatic cancers were compared. RESULTS: Of the 67 patients, the
      primary tumors were identified in 39 (53.7%) by (18)F-FDG PET-CT, and 36 of them
      were confirmed by pathology or follow-up. Thirteen distant metastases and
      seventeen lymphatic metastases were newly discovered by whole body (18)F-FDG PET
      CT imaging. The SUV of metastatic tumors was significantly lower than that of
      primary tumors (t = 3.470,P = 0.001) and closely correlated with that of the
      primary tumors (r = 0.738, P = 0.000). CONCLUSION: (18)F-FDG PET-CT is not only
      valuable in identifying the unknown primary tumor in patients with metastatic
      carcinoma, but can also be used to reveal the biological characteristics of the
      tumors by functional imaging.

PMID- 19173916
TI  - [Evaluation of immunohistochemical markers for differential diagnosis of
      hepatocellular carcinoma from intrahepatic cholangiocarcinoma].
AB  - OBJECTIVE: To evaluate the significance of a panel of immunohistochemical markers
      for distinguishing hepatocellular carcinoma (HCC) from intrahepatic
      cholangiocarcinoma (ICC). METHODS: Ten markers including hepatocyte paraffin 1
      (Hep Par 1), polyclonal carcinoembryonic antigen (pCEA), CD34, CD10, CD105,
      multidrug resistance-associated protein-3 (MRP-3), cyclooxygenase-2 (COX-2),
      mucinous glycoprotein-1 (MUC-1), aquaporin-1 (AQP-1) and CK19 were
      immunohistochemically stained in the samples from 90 surgically resected HCC and
      80 ICC, respectively,and the positive rate of their expression were compared
      statistically. RESULTS: The positive expression rates of Hep Par 1, pCEA, CD34,
      CD10, CD105, MRP-3, COX-2 were 85.6%, 82.2%, 87.8%, 18.9%, 8.9%, 11.1% and 48.9%,
      respectively, in HCC. While the positive expression rates of MUC-1, AQP-1 and
      CK19 were 73.8%, 65% and 92.5%, respectively, in ICC. CONCLUSION: Based on our
      results, Hep Par 1 and CD34 can be used as the first line markers, and pCEA and
      COX-2 as the second line makers, for differential diagnosis of hepatocellular
      carcinoma from intrahepatic cholangiocarcinoma. While MUC-1 and CK19 can be used
      as the first line markers and AQP-1 as the second one for the differential
      diagnosis of intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

PMID- 19173917
TI  - [Ultrasound-guided percutaneous radiofrequency ablation of hepatic malignancies
      with cool-tip needle].
AB  - OBJECTIVE: To investigate the efficacy, indication and complication of
      radiofrequency ablation (RFA) with cool-tip needle in patients with hepatic
      malignancies. METHODS: 421 patients with hepatic malignancies underwent
      ultrasound-guided RFA with cool-tip needle under local anaesthesia. The tumor
      size was from 1.0 to 15 cm in diameter with an average diameter of 4.3 cm.
      RESULTS: The complete ablation (CA) rate was 91.4% (382/418) in the patients with
      a tumor < 3 cm, 78.9% (97/123) in those with a tumor of 3 to 5 cm and 37.6%
      (35/93) in the patients with a tumor > 5 cm. No patient died or changed to
      celiotomy during the 1121 times of RFA for 634 lesions in 421 patients. No
      hemorrhage occurred in any of these patients after the RFA treatment. The
      complications included abdominal pain in 32.3% (136/421), nausea in 9.0%
      (38/421), fever in 34.9% (147/421) and biliary leakage in 0.2% (1/421) of the
      patients. CONCLUSION: Ultrasound-guided percutaneous radiofrequency ablation with
      cool-tip needle is effective and safe in the treatment of liver tumors.

PMID- 19173918
TI  - [Diagnosis and surgical treatment of giant intrathoracic solid tumors].
AB  - OBJECTIVE: To summarize the experience in diagnosis and surgical treatment of
      giant intrathoracic solid tumors. METHODS: The data of surgically treated 36
      patients with giant intrathoracic solid tumors were analyzed, including 19 males
      and 17 females. Complete resection was achieved in 34 cases with superior vena
      cava angioplasty in 3 cases and ligation of the left anonymous vein in 2 cases.
      Six patients received postoperative radiotherapy. RESULTS: The symptoms in 32
      cases were significantly improved. Two patients (5.6%) died of postoperative
      respiratory infection and failure. The mean postoperative hospital stay was 14.2
      days. Pulmonary edema occurred in 6 cases due to rapid decompression of the lung.
      Pathological results showed that 25 cases had benign tumors and 11 had
      malignancy. During the follow-up of 1 to 22 years, all patients with benign
      tumors were still alive, but the patients with malignant tumors had a mean
      survival time of only 2.1 years. CONCLUSION: Surgical treatment for giant
      intrathoracic solid tumors is suggested whenever technically possible. Even
      though a tumor can not be completely resected, satisfied results could still be
      achieved if combined with postoperative radiotherapy. Proper anesthesia,
      satisfied exposure with a suitable incision, appropriate resection pattern and
      hemostatic method are the keys for successful surgical treatment.

PMID- 19173919
TI  - [Analysis of cavitation of advanced NSCLC treated by rh-endostatin combined with
      NP chemotherapy].
AB  - OBJECTIVE: To study the significance of intra-tumoral cavitation in the patients
      with advanced NSCLC treated by rh-endostatin plus NP chemotherapy. METHODS: Fifty
      seven patients with advanced NSCLC were randomly assigned to receive chemotherapy
      with rh-endostatin plus NP or NP alone. The numbers of activated circulating
      endothelial cells (aCECs) were measured by flow cytometry. Chest computed
      tomography was performed to evaluate the efficacy after 2 cycles of chemotherapy.
      RESULTS: Cavitation occurred in 5 of 29 patients in the rh-endostatin plus NP
      group, but not in any case of the NP group. Of the 5 patients, there were 2 males
      and 3 females, with pathological types of 3 adenocarcinomas, 1 adenosquamous cell
      carcinoma and 1 sarcomatoid carcinoma. All of these 5 cases had a peripherally
      located tumor in the CT scan. There was only one cavity in each case and most of
      these were roundish. Four cavities were situated in the center of the tumor and
      another one was eccentric. There were 3 cavities with thin wall and 2 with thick
      wall. Their average diameter was 2.7 cm. No hemoptysis occurred in these 5
      patients. The blood-supply of the tumors showed by perfusion CT images was
      inhibited in 3 cases after treatment. The average number of aCECs decreased from
      323.2/10(5) to 33.0/10(5) after treatment. CONCLUSION: Intratumoral cavitation is
      a peculiar imaging characteristics after anti-angiogenic therapy, which may be
      caused by inhibition of blood-supply to the tumor. CT perfusion imaging and
      measurement of activated circulating endothelial cells may be helpful to predict
      the efficacy of anti-angiogenic therapy combined with chemotherapy.

PMID- 19173920
TI  - [Evaluation of recombinant human thrombopoietin in the treatment of chemotherapy
      induced thrombocytopenia in lung cancer patients].
AB  - OBJECTIVE: To evaluate the efficacy and safety of recombinant human
      thrombopoietin (rhTPO) in treatment for chemotherapy-induced thrombocytopenia in
      patients with lung cancer. METHODS: Fifty-one lung cancer patients with platelet
      count < 100 x 10(9)/L after chemotherapy were enrolled into this study. They were
      divided into three groups: mild, moderate and severe thrombocytopenia groups
      according to the platelet count. rhTPO was subcutaneously administered at a
      dosage of 300 microg kg(-1) d(-1) until the platelet count >or= 100 x 10(9)/L or
      absolute value of platelet count >or= 50 x 10(9)/L. Laboratory tests included
      routine blood count, serum biochemistry, and blood coagulation test. RESULTS: The
      duration of the chemotherapy-induced thrombocytopenia was significantly shorter
      in the mild group than that in the moderate and severe groups (P < 0.01). After
      administration of rhTPO, the time of declined platelet count beginning to recover
      was also significantly shorter in the mild group than that in the moderate and
      severe groups (P < 0.01). There was a statistically significant difference in
      platelet transfusion needed among the three groups (P < 0.01). However, no
      significant difference was found among the three groups in the time of rhTPO
      treatment (P > 0.05) and platelet count improvement (P > 0.05). CONCLUSION:
      Recombinant human thrombopoietin can be effectively and safely administered to
      deal with grade III/IV chemotherapy-induced thrombocytopenia in lung cancer
      patients with mild adverse effects.

PMID- 19173922
TI  - [Study on over-weight, obesity and the exposure to stroke risk factors among 40
      year olds and over in a community-based population].
AB  - OBJECTIVE: To describe the distribution of over weight and obesity to discover
      the level of exposure on risk factors of stroke among people aged 40 and over, in
      a community-based population. METHODS: From 2003 to 2004, people aged > or = 40
      years in a community of Fengxian district in Shanghai were selected by cluster
      sampling. Out of 11,791 individuals who were selected, 10,565 met the inclusion
      criteria and responded to the investigation. By face to face interview, a cross
      sectional survey was carried out, using a questionnaire for risk factors of
      stroke. Height, weight and blood pressures were measured and cerebrovascular
      hemodynamic parameters (CVHP) were checked. Age and gender distribution of over
      weight and obesity in the population were described. Using 60 year as cut-off
      point, participants were grouped into three: normal, over weight and obesity by
      body mass index. Level of stroke risk factor exposure between groups was compared
      and logistic regression model was used for multiple analyses. RESULTS:
      Proportions of over weight and obesity were 28.5 percent and 4.1 percent in male
      and 26.3 percent and 4.2 percent in female (P = 0.045). Systolic and diastolic
      blood pressure in over weight group were (132.5 +/- 19.4) mm Hg and (83.9 +/-
      10.5) mm Hg (1 mm Hg = 0.133 kPa), which were higher than that in normal weight
      group and lower than that in obese group (P < 0.05). Exposure rate of heart
      disease, family history of stroke in < 60 year old group and diabetes in > or =
      60 year group increased along with the increase of weight. Exposure rate of
      hypertension, abnormality of CVHP score in both age groups were also increased
      with the increase of weight. Data from multiple logistic regression indicated
      that hypertension, family history of stroke and heart disease, CVHP score below
      75 points, sex and age were independent factors of over weight and obese.
      CONCLUSION: The prevalence of over weight or obesity in a community-based
      population among aged 40 years or over was around 30 percent. The overall
      exposure rate of stroke risk factors were increasing along with the increase of
      weight, especially for those in the middle age.

PMID- 19173923
TI  - [A cross-sectional study on smoking behavior and nicotine dependence among
      workers in Guangzhou].
AB  - OBJECTIVE: To investigate smoking behavior and nicotine dependence (ND), so as to
      provide evidence for tobacco control in workers. METHODS: A cross-sectional study
      to investigate smoking behavior and ND in 668 workers with different job
      assignment in Guangzhou. Fagerstrom Test for Nicotine Dependence and logistic
      regression model were used to analyze the association between ND and some risk
      factors. RESULTS: (1) The prevalence of ever-smoking was 65.0% (348/535) in men
      (55.5% daily smokers, 5.4% occasional smokers and 4.1% ex-smokers), and 3.0%
      (4/133) in women. The prevalence of current smoking for manual workers and safety
      officers were 67.6% and 64.5% respectively. (2) Among daily and occasional
      smokers, 66.7% and 89.7% of them had low ND respectively. Among daily smokers, ND
      increased with the duration of smoking. Manual workers and officers had higher
      ND. CONCLUSION: The prevalence of smoking was relatively high in workers and
      officers and in men. However, majority of the smokers were with low ND and could
      be the prioritized target for a primary smoking cessation intervention program.

PMID- 19173924
TI  - [Association between the concentration of particulate matters and the hospital
      emergency room visits for circulatory diseases: a case-crossover study].
AB  - OBJECTIVE: To explore the association between the concentration of particulate
      matters with an aerodynamic diameter of < 10 microm (PM(10)) and the hospital
      emergency room visits for circulatory diseases (International Classification of
      Diseases, tenth vision ICD-10:I00-I99) in Beijing, China. METHODS: We collected
      data for daily hospital emergency room visits of circulatory diseases (ICD-10:I00
      I99) from Peking University Third Hospital and from the ambient air PM(10)
      through the Beijing Municipal Environmental Monitoring Center. A time-stratified
      case-crossover design was used to evaluate associations between circulatory
      disease health outcomes and PM(10). RESULTS: The no-lagged unidirectional case
      crossover design with 1:4 matched pairs had the highest odds ratios (ORs) between
      PM(10) and the hospital emergency room visits for circulatory diseases. After
      adjusting the temperature and the relative humidity, a 10 microg/m(3) increased
      in the PM(10) were found associated with the emergency room visits on value of
      ORs of 1.006(95%CI: 1.003 - 1.008) for the total circulatory diseases (ICD-10:I00
      I99), 1.003 (95%CI: 0.996 - 1.010) for coronary heart disease (ICD-10:I20-I25),
      1.005 (95%CI: 0.997 - 1.013) for cardiac arrhythmia (ICD-10:I47-I49), 1.019
      (95%CI: 1.005 - 1.033) for heart failure disease (ICD-10:I50), and 1.003 (95%CI:
      0.998 - 1.007) for cerebrovascular diseases (ICD-10:I60-I69), respectively.
      CONCLUSION: These findings suggested that elevated levels of ambient PM(10) were
      positively associated with hospital emergency room visits for the total number of
      circulatory diseases and heart failure disease.

PMID- 19173925
TI  - [Correlation between psychological well-being and social support to those settled
      immigration from Three Gorges Reservoir areas].
AB  - OBJECTIVE: To investigate the psychological well-being and the correlation
      between psychological status and social support among the settled immigrations
      from Three Gorges Reservoir areas. METHODS: A cluster randomized sampling was
      selected and 646 objects were interviewed with Basic Situation Scale, Symptom
      Check-list 90 (SCL-90) and Social Support Rating Scale (SSRS). RESULTS: Our
      findings from the results of SCL-90 revealed that the positive rate of
      psychological problem was higher in settled immigration than that of local
      permanent residents (chi(2) = 4.10, P = 0.04). The differences of scores on 6
      factors including compulsion (t = 2.644, P = 0.009), interpersonal-sensitivity (t
      = 3.220, P = 0.001), depression (t = 2.684, P = 0.008), anxiety (t = 3.003, P =
      0.003), paranoid-ideation (t = 3.246, P = 0.001), psychoticism (t = 2.088, P =
      0.038) and the total score (t = 2.506, P = 0.013) were significantly different in
      female between the two groups. There were also significant differences of 10
      factors score and total score (t = 4.114, P = 0.000) noticed between the two
      groups in age < or = 50 (P < 0.05) and the differences of 4 factors score
      including somatization (t = 2.777, P = 0.006), interpersonal-sensitivity (t =
      2.384, P = 0.018), hostility (t = 3.174, P = 0.002), paranoid ideation (t =
      2.611, P = 0.010). The total scores (t = 2.125, P = 0.034) were significantly
      different between the two groups in illiteracy and having received primary school
      education. Other than compulsion factor (t = 1.884, P = 0.061) and phobic anxiety
      factor (t = 0.979, P = 0.328), there were significant differences on other
      factors and the total score between the two groups in non-farmers (P < 0.05).
      Except compulsion (r = -0.103, P > 0.05), hostility (r = -0.084, P > 0.05) and
      paranoid ideation factor (r = -0.071, P > 0.05), the negative correlations were
      obvious between the total score, other factors score and social support (P <
      0.05). The negative correlation was obvious between somatization (r = -0.128, P <
      0.05), depression (r = -0.140, P < 0.05), anxiety (r = -0.137, P < 0.05), phobic
      anxiety (r = -0.120, P < 0.05), additional factor (r = -0.143, P < 0.05) total
      score (r = -0.137, P < 0.05) and subjective support. The correlation coefficient
      was not significant between SCL-90 total score, 10 factors score and that of
      objective support (P > 0.05). CONCLUSION: The psychological status of settled
      immigration was not satisfactory and closely correlated to psychological mental
      level and social support.

PMID- 19173926
TI  - [Levels of transition on maternal transferred measles antibody in infants in 3
      cities in China].
AB  - OBJECTIVE: To understand the epidemiological characteristics of age distribution
      of measles and related policies on measles vaccines (live; MV) in infants through
      analyzing the antibody levels of comparison in maternal-infant pairs. Transition
      of immunity in infants was also studied to provide theoretic basis for measles
      immunization strategy and to reduce the incidence of month-old infants. METHODS:
      In cities of Ningbo, Harbin, and Jinan from Zhejiang, Heilongjiang and Shandong
      provinces, data was collected from 2004 to 2007 and analyzed regarding the
      epidemic situation of measles. Studies on maternal-transferred measles antibody
      were carried our sero-epidemiologically. RESULTS: Most of the measles cases were
      found among babies younger than 12 months, and the incidence of < 1 year olds had
      been increasing. The distribution was dominated by 5 - 8 month olds in infant
      measles cases. The positive rate and GRMT of measles antibody in newborns were
      89.3 percent and 738.93. The positive rate of the measles antibody and GMRT of
      the 6-month infant were 6.9% and 6.89, while 6.7% and 3.69 in 8-month infant.
      There was a declining trend of the positive rate of the measles antibody during
      the newborns to 8-month infant. The positive rate and GRMT of measles antibody in
      mothers were 84.3 percent and 516.94. Mother's measles antibodies mainly to be at
      low and moderate level, which accounted for 50.4 percent and 30.3 percent
      respectively, the correlation coefficient between mother and infant was 0.840.
      CONCLUSION: Maternal-transferred measles antibody decreased as the growth of
      infants. The positive rates of measles antibody were quite low in 6-month and 8
      month olds which were the age range that needs most attention.

PMID- 19173927
TI  - [Reliability and validity regarding the Chinese version of the International
      Physical Activity Questionnaires (long self-administrated format) on women in
      Chengdu, China].
AB  - OBJECTIVE: To test the reliability and validity of International Physical
      Activity Questionnaires (long self-administrated format) (IPAQ), Chinese version
      on women of 12 - 44 years old, in Chengdu city. METHODS: Clustered sampling was
      used, according to the age distribution of investigated population. One
      community, one university and two middle schools (including one high school and
      one junior high school) in Chengdu were selected. The reliability study was
      conducted in a 28-day period. Participants were contacted three times within 28
      days (on the 1(st), the 8(th) and the 28(th) day respectively). In the validity
      study, participants completed the same questionnaire and Bouchard physical
      activity diary (PA diary) each day for seven days between visit 1 and visit 2
      before comparing the IPAQ's result with Bouchard physical activity diary's for
      validity study. Pearson or Spearman' correlation coefficients were calculated for
      validity and interclass correlation coefficients for reliability according to
      date distribution. RESULTS: (1) One hundred and eighty six participants were
      recruited for the reliability study. All of them completed the first
      questionnaire with 143 (76.88%) and 172 (92.50%) finished the second and third
      questionnaires. One hundred and fifty eight participants were recruited in the
      validity study. Qualified questionnaire accounted for 90.59% (143). (2) Results
      from the test-retest reliability of the Chinese version of long self
      administrated format (IPAQ) showed: the ICC after one week ranged from 0.7373 to
      0.972 (mean: 0.870) which were higher than those interval's reliability [ICC =
      0.472 - 0.948 for three weeks interval (mean: 0.721), and 0.473 - 0.925 for four
      weeks interval (mean: 0.696)]. The ICCs of three weeks interval and four weeks
      interval were not significantly different. ICCs for vigorous physical activity
      and leisure time physical activity were the best. (3) The validity for different
      intensity, total physical activity and sitting time showed the correlation
      coefficients between IPAQ and PA diary ranged from 0.445 to 0.696, with
      correlation for vigorous physical activity the best (r = 0.696). CONCLUSION: IPAQ
      C seemed a reliable and validated measure of physical activity for 12 - 44 year
      old women in Chengdu city.

PMID- 19173928
TI  - [Research on the causes of physical disabilities among children aged 0 - 14, in
      China].
AB  - OBJECTIVE: To understand the present situation and the changes on causes of
      physical disabilities among children aged 0 - 14 years for the past 20 years in
      China. METHODS: Data on children with physical disabilities aged 0 - 14 years
      from The China National Sample Survey on Disability in 2006 and 1987, were
      analyzed and compared. RESULTS: The categories on the causes of children with
      physical disabilities aged 0 - 14 could be grouped as: congenital diseases and
      eccyliosis, with injury factors, other factors and disease factors. The specific
      causing-disability rates were 0.257%, 0.066%, 0.055% and 0.041% respectively.
      Cerebral palsy rated the highest specific causing-disability as 0.129% in all of
      the causes. Compared with 1987, the specific causing-disability rate of
      congenital diseases and eccyliosis had an obvious increase while the rates of
      disease factors and other factors showed a substantial decrease. The top five
      causes of children with physical disabilities aged 0 - 14 years in China were
      cerebral palsy, deformity, other kinds of traumas, congenital diseases and
      eccyliosis in 2006. Other causes, postpoliomyelitis muscular atrophy, deformity,
      other kinds of traumas and unknown causes were the top five in 1987. The age
      specific top five causes were basically the same as the total top five causes of
      children aged 0 - 14 years with physical disabilities in 1987 and 2006, so as the
      same relationship between sex-specific top five causes and total top five.
      CONCLUSION: Congenital diseases and eccyliosis were the main causes of 0 - 14
      year-old children with physical disabilities, and cerebral palsy had the highest
      specific causing-disability rate while injury factors gradually became the major
      one.

PMID- 19173929
TI  - [A survey on reproductive health related sexual behavior among middle school
      students in Luoyang city].
AB  - OBJECTIVE: To explore the appropriate ways and contents of reproductive health
      education for middle school students and to understand reproductive health
      related sexual behavior and influencing factors among middle school students.
      METHODS: Reproductive health related sexual behavior was evaluated among junior
      and senior middle school students in Luoyang by cluster sampling. The statistical
      software of SAS 8.1 was adopted for data analyses. Sexual behavior and
      influencing factors were analyzed by logistic regression. RESULTS: Critical
      sexual behaviors were found significantly higher in senior students, including
      masturbation, sexual fantasy and sexual intercourse than that in junior students
      (P < 0.05), and boys had higher prevalence than girls (P < 0.05). Results from
      multivariate logistic regression model analyses indicated that incidence rate of
      sexual behavior among those who ever having had experiences was higher than those
      who were inexperienced (OR = 2.62, 95%CI: 1.21 - 5.66). Incidence rate of sexual
      behavior was related to access of reproductive health and STD/AIDS knowledge (OR
      = 3.09, 95%CI: 1.43 - 6.51). In addition, incidence rate of sexual behavior was
      related to attitude and relation of amour between boys and girls (OR = 2.24,
      95%CI: 1.32 - 3.75). CONCLUSION: Awareness on reproductive health knowledge among
      middle school students was not enough. Marginal sexual behaviors as masturbation
      and sexual fantasy had not been correctly and openly discussed to avoid
      inappropriate sexual activities.

PMID- 19173930
TI  - [Study on the declining physical functions and its influencing factors among the
      Chinese elderly aged 65 years and over].
AB  - OBJECTIVE: To understand the declining pattern of physical activities on daily
      living (PADL) and instrumental activities of daily living (IADL) and its
      influencing factors among the Chinese elderly aged 65 years and over. METHODS:
      Using data from 2002 and 2005 of the Chinese Longitudinal Health Longevity Study
      (CLHLS), 6761 Chinese elderly with fully independent PADL in 2002 and 3556
      Chinese elderly with fully independent IADL in 2002 were studied. RESULTS: Data
      showed that the male elderly with fully dependent IADL at baseline in 2002
      declined to 59.3% but kept the IADL in full independent in 2005, while that of
      female elderly were 51.8% still keeping the IADL full independent in 2005. Male
      elderly who at baseline with the PADL fully dependent in 2002 declined to 87.1%
      but kept the PADL full independent in 2005, while that of female elderly were
      81.5% keeping the PADL full independent in 2005. There were only 70.0%, 47.0%,
      24.0% and 15.0% elderly keeping the IADL full independent among the age groups of
      65 - 74, 75 - 84, 85 - 94 and 95 - 105, respectively, from 2002 to 2005; while
      there were 95.0%, 87.0%, 74.0% and 55.0% elderly keeping the PADL full
      independent among the above age groups of 65 - 74, 75 - 84, 85 - 94 and 95 - 105,
      from 2002 to 2005. Age, numbers of episodes that suffering from serious illness
      in the past two years and cognitive ability were significantly associated with
      IADL or PADL had a decline after controlling for sex, socioeconomic factors in
      the multinomial logistical regression analysis among the Chinese elderly aged 65
      years and older, during the period from 2002 to 2005. CONCLUSION: The declining
      physical functional status among the 65 and older elderly went severe with age in
      China, with IADL more severe than that of PADL. Chinese female elderly suffered
      more in PADL or IADL than that of male elderly. Age, numbers of episode that
      suffering from serious illness in the past two years and cognitive ability were
      considered as predictive factors of functional status among the Chinese elderly.
      However, gender, living conditions, education background and marital status that
      appearing to be the significant predictors only seen in partial IADL/PADL
      declining models.

PMID- 19173931
TI  - [A long-term evolution on the epidemiological characteristics of leprosy, towards
      the goal of its elimination in 1949 - 2007 in China].
AB  - OBJECTIVE: To understand the epidemiological characteristics of leprosy during
      the evolution of the disease, towards the goal of elimination for the past 50
      years and longer, so as to provide experiences for accelerating eradication of
      leprosy in China. METHODS: Data were collected from National Surveillance System
      of Leprosy which was composed annually of all the data from county-based leprosy
      unit reporting system. All the data were reviewed retrospectively. RESULTS: A
      total number of 487 900 leprosy patients were reported from 1949 to 2007 in
      China. The case detection rate reduced from the highest of 5.56/100 000 in 1958
      to the lowest of 0.12/100 000 in 2007. Leprosy patients mainly distributed in
      mountain areas in Yunnan, Guizhou, Sichuan, Guangdong Guangxi, Hunan and Jiangxi
      provinces with warm and damp climate and underdeveloped economy. After more than
      50 years of leprosy control efforts, the case detection rate declined quickly in
      provinces in the eastern and the southern parts but very slowly in provinces in
      the western and the southwestern part of China. The ratio of relapsed patients to
      newly detected ones increased from 1:139 in 1960s' to 1:10 after 1980s',
      annually. The proportion of child cases among newly detected patients had been 3%
      - 4% since 1968. In the recent 20 years, the proportion of new patients with
      positive skin smear gradually increased and the rate of disability grade two
      reached 20% and more. The average age of new patients upon diagnosis was 45 years
      old in the east coastal provinces but only 38 years old in the southwest
      provinces. A new finding was that some new patients detected in the east coastal
      provinces were immigrants from the southwestern provinces. CONCLUSION: With
      continuous socio-economic development and active efforts on leprosy control, the
      prevalence of leprosy gradually declined despite the long evolution period. Some
      negative events seemed to have influenced the trend of case detection.

PMID- 19173933
TI  - [Study on the changes of incidence rates on birth defects through hospital based
      surveillance program in Guangdong province during 1997-2007].
AB  - OBJECTIVE: To analyze the tendency of hospital based surveillance incidence rates
      of birth defects in Guangdong province to provide reference evidence for related
      intervention program. METHODS: Data from hospital based birth defects
      surveillance of Guangdong province during 1997 - 2007 were analyzed
      retrospectively. RESULTS: The overall surveillance rates of birth defects in
      Guangdong province showed an increasing trend form 98.9 per 10 000 birth in 1997
      to 244.2 per 10 000 birth in 2007. Among the frequently seen birth defects, the
      rate of congenital heart diseases increased sharply, but the rates of congenital
      talipes equinovarus, polydactyly, cleft lip with/without cleft palate showed a
      slight increasing trend. It seemed that there was a significant difference
      between different maternal age interval and gender of the infants. Mother's
      illness, drug use, and exposure to environment harmful factors in early pregnancy
      stage, high maternal age, negative bearing history were the suspect risk factors
      for birth defects. CONCLUSION: The increasing trend of surveillance rate of birth
      defects seemed to be comprehensively affected by the factors as: method being
      adopted, target and extension of birth defects surveillance, technology used for
      diagnosis, kinds of risk factor, and quality control on surveillance programs.

PMID- 19173935
TI  - [Epidemiological investigation on natural infection to Borna disease virus (BDV)
      among horses in Yili, Xinjiang].
AB  - OBJECTIVE: To investigate the epidemiological pattern of Borna disease virus
      (BDV) infection in horses and to analyze the phylogenetic tree of derived BDV in
      Yili, Xinjiang. METHODS: We established a modified nested RT-PCR (nRT-PCR) to
      detect BDV p24 segment in peripheral blood mononuclear cells (PBMCs) and brain
      tissues of 120 horses in Yili, Xinjiang. Positive products were analyzed by
      sequencing and homology analysis. RESULTS: The positive rate of BDV infection was
      2.5% in both PMBCs and brain tissues at the same time. The gene sequence revealed
      in positive PCR samples was more than 93%, identical to that of BDV derived from
      horses in other countries. We also noticed a high degree of identity (> 98%) to
      standard strain He/80 in gene sequence of positive PCR samples. CONCLUSION: Our
      study found the presence of BDV natural infection in horses in Yili. The endemic
      BDV had a high degree of identity to standard strain He/80.

PMID- 19173936
TI  - [The emergence of candidate pathogenicity island 89K DNA sequence of
      Streptococcus suis isolated from sporadic patients in Zhejiang province].
AB  - OBJECTIVE: To identify the presence of candidate pathogenicity island 89K DNA
      sequence of Streptococcus suis serotype 2 (SS2) strains isolated from patient in
      Zhejiang province. METHODS: Genes and DNA fragments were amplified by PCR, using
      specific primers, and three amplified fragments of the 89K sequence were directly
      sequenced. The results were analyzed using software related to bioinformatics and
      epidemiology. RESULTS: 8 strains of SS2 all contained 89K sequence, cps2J and mrp
      virulent genes, and species-specific 16S rDNA. 3 amplified fragments of 89K
      candidate pathogenicity island of SS2 ZJ0501 were above 99% similar to SS2 strain
      identified from outbreaks in Jiangsu in 1998, and the gene fragment of coding DNA
      recombinant protein in the 89K sequence was highly homological with that of S.
      dysgalactiae and S.agalactiae. CONCLUSION: In recent years SS2 strains isolated
      from patients with clinical symptoms in Zhejiang province had been detected to
      have contained candidate pathogenic 89K DNA fragment.

PMID- 19173937
TI  - [Molecular characteristics and its evolution of the complete genome of avian
      influenza H5N1 virus isolated in Zhejiang province from 2002 to 2006].
AB  - OBJECTIVE: To analyze the molecular characteristics and evolution reassortment of
      the complete genome of avian influenza H5N1 virus isolated in Zhejiang province
      in recent years. METHODS: Complete genomes of avian influenza H5N1 viruses
      isolated in Zhejiang province from 2002 to 2006 were sequenced. Molecular and
      evolution reassortment characterization of these virus strains were analyzed by
      Mega 3.0 bioinformatics software. RESULTS: Through study on the HA genes from all
      these strains, our data revealed that there were multiple basic amino acids at
      the cleavage site, which was typical for HPAIV. Compared with Gs/Guangdong/1/96,
      all these strains had a 20 amino acid deletion in the stalk of the NA, except for
      Dk/Zhejiang/2/02 and Ck/Zhejiang/8/03. Results from phylogenetic analysis showed
      that from 2002 to 2003 the H5N1 viruses belonged to the genotype of B, W, X, Y,
      Z, and other genotypes were prevailed in corresponding year. However, different
      gene fragments of several strains belonged to different genotypes. CONCLUSION:
      Recombinant might be widespread among the poultry in Zhejiang province. The
      genetic genes of viruses isolated after 2005, the Ck/Zhejiang/24/05 and
      Zhejiang/16/06 strains were almost all originated from the FJ-like genotype
      stably.

PMID- 19173938
TI  - [Sequencing on products of Oncomelania hupensis through simple sequence repeat
      anchored polymerase chain reaction amplification].
AB  - OBJECTIVE: To analyze the sequence of microsatellite and the flanking sequence
      from four populations of Oncomelania hupensis. METHODS: We cloned 159 SSR-PCR
      amplification products of a commonly used primer, (CA)(8RY), using O. hupensis
      genomic DNA as template, and sequenced 82 products. RESULTS: The sequences
      obtained were novel O. hupensis genomic sequences but not repeat simple sequence.
      It was observed that 36 out of 82 clones contained microsatellites between
      priming sites. The flanking sequences of certain microsatellite were invariant.
      Both (GA/CT)(n) and (TTAGGG/CCCTAA)(n) were found in four populations of O.
      hupensis. However, (CAA)(n) were found only in O. hupensis from Fuqing, Fujian
      province and (TCTCTG)(n) were found only in O. hupensis from Guichi, Anhui
      province and (GAA/TTC)(n), (CAA/TTG)(n), (CAT)(n) were found only in O. hupensis
      from Puge, Sichuan province. CONCLUSION: The results obtained by SSR-PCR should
      not be interpreted as the amplification of microsatellite loci, and analytical
      rules similar to those for Random Amplified Polymorphic DNA should be used. SSR
      PCR could not make the most of the priority of microsatellite. It seems better to
      amplify the microsatellites with the primers designed on the basis of the
      flanking sequence.

PMID- 19173939
TI  - [Genomic analysis of an unknown pap genotype from uropathogenic Escherichia coli
      4030 strain].
AB  - OBJECTIVE: To investigate the differences between the sequences of papA and papG
      of UPEC4030 strain and the related genes, to better understand the genetic
      variation of UPEC4030 papA and its combination forms with papG so as to identify
      if it was a new genotype. METHODS: Cloning and sequencing methods were used to
      analyze the sequences of papG and papA of UPEC4030 strain and to compare their
      related sequences. RESULTS: Through sequence analysis of papA, it was revealed
      that there was a 722 bp gene, encoding 192 amino acid polypeptide. The overall
      homology of the papA genes between UPEC4030 and the standard strains of ten F
      types were 36.11% - 77.95% and 22.20% - 78.34% at nucleotide and deduced amino
      acid levels. Homology between the sequences of reverse primers and the
      corresponding sequence of UPEC4030 papA was 10.00% - 66.67%. The results
      confirmed that UPEC4030 strain contained a novel papA variant. Through sequence
      analysis of UPEC4030 papG, we revealed a 1100 bp gene, encoding 337 amino acid
      polypeptide. The homology of the papG genes between UPEC4030 and UPEC IA2, the
      standard strain, was 99.00% at nucleotide level and 99.11% at deduced amino acid
      and UPEC4030 strain carried class II genotype of papG. CONCLUSION: UPEC4030
      strain contained an unknown papA variant or the new genotype and carried class II
      genotype of papG. The pathogenic mechanism and epidemiology call for further
      study.

PMID- 19173940
TI  - [A 10-year-review (1998 - 2007) on 3449 cases of osteoporotic hip fractures:
      trend of hospitalization and inpatient costs].
AB  - OBJECTIVE: The purpose of this retrospective research was to analyze the trend of
      hospitalized prevalence in the past 10 years (1998 - 2007) and to estimate
      resource utilization associated with osteoporotic hip fractures, including
      hospital length of stay and inpatient costs in Guangzhou, China. METHODS: 3449
      patients aged 50 years and older, hospitalized for primary diagnose of hip
      fractures in both hospitals in the past ten years were included in our study.
      Completed data was obtained retrospectively from the hospital medical records.
      Clinical parameters such as sex-specifics, hospital length of stay, inpatient
      costs, and the constitutions of the inpatient costs were analyzed with multiple
      statistics methods and regressions. RESULTS: Over the 10-year study period, the
      number of hospitalizations for hip fractures increased with a curve model. Male
      and female ratio was 1:1.95 with an average age of the patients as 76.32 +/- 9.52
      years old. Average hospital length of stay was 23.59 +/- 13.48 days with no
      significant difference between males and females, years of admission and the
      different diagnoses. The number of hospitalization went to the top at the age of
      70 to 79 years old (38.45%), followed by 80-89 years old (33.08%). Femoral neck
      fractures was significantly more than that of inter-trochanteric fractures in
      those patients aged 50 to 79 years (P < 0.01) but less than those
      intertrochanteric fractures aged 90 years and older (P < 0.05). Average inpatient
      costs is about 23.52 +/- 17.00 thousand Yuan (RMB) (femoral neck fractures is
      about 25.09 +/- 17.62 thousand Yuan and intertrochanteric fracture is 21.44 +/-
      15.92 thousand Yuan) of which treatment costs (included implants, materials used
      in the theatre and routinely care of the wound) contributed 52%, pharmacy
      intervention 25%, operation 6%, ward expenditure 5%, radiology and physical
      investigation 5%, and chemistry test 4%. The inpatient cost went to a peak at the
      age of 60 - 69 years old and were significantly correlated with the hospital
      length of stay. The cost increased every year in the past 10 years by 6.18%.
      CONCLUSION: These results emphasized that the growing economic impact arising
      from the inpatient treatment of osteoporotic hip fractures and most of which
      related to treatment cost (include implants, materials used in the theatre and
      routinely care of the wound), and drugs and always correlated to length of
      hospital stay. Cost control should be paid more attention to the implants and
      drugs.

PMID- 19173941
TI  - [A Meta-analysis on the association between adiponectin gene 45T/G/276G/T
      polymorphisms and type 2 diabetes in Chinese population].
AB  - OBJECTIVE: Association between the 45T/G and 276G/T single nucleotide
      polymorphisms of adiponectin gene and the occurrence of type 2 diabetes in
      Chinese population was studied. METHODS: 20 studies consisting 22 case-control
      comparisons about 45T/G polymorphism and nine case-control studies about 276G/T
      polymorphism that were based on our inclusion criterion and available in the
      literature were reviewed. RESULTS: Results from Meta-analysis demonstrated a
      large heterogeneity among the studies both on 45T/G and 276G/T polymorphisms and
      a significant association was observed between 45T/G polymorphism at exon 2 of
      the adiponectin gene and type 2 diabetes among the Chinese population.45G allele
      appeared to be one of the genetic risk factors for susceptibility to type 2
      diabetes with a random effects odds ratio (OR) of 1.43 (95%CI: 1.17 - 1.75), and
      the G allele carriers were more susceptible to the disease with an OR of 1.38
      (95%CI: 1.04 - 1.84). Results from Meta-analysis, however, showed no association
      between the 276G/T polymorphism and type 2 diabetes in the Chinese population,
      while the random effects OR of the allele 276T to susceptibility of disease was
      0.83 (95%CI: 0.61 - 1.13). CONCLUSION: The current paper on Meta-analysis
      demonstrated a correlation between the 45T/G single nucleotide polymorphism and
      the occurrence of type 2 diabetes in Chinese population, which was different from
      the findings that such an association with 276G/T polymorphism could not be
      demonstrated in the same ethnic population.

PMID- 19173942
TI  - [A Meta-analysis on the risk factors of perinatal congenital heart disease in
      Chinese people].
AB  - OBJECTIVE: To investigate the main risk factors related to the incidence of
      perinatal congenital heart disease (CHD) in Chinese people. METHODS: Results on
      the risk factors of CHD in 12 papers were analyzed by Meta-analysis method. The
      cumulative cases and controls were 3436 and 3976, respectively. The calculation
      methods of the combined odds ratio (OR) and 95% confidence interval (CI) were
      determined according to the homogeneity test. RESULTS: The pooled OR values of
      single-factor-analysis were as follows: spiritual stimulus (4.55), maternal
      exposures to pesticides (4.85), negative life events (5.39) during pregnancy,
      cold (3.18) during early pregnancy, exposure to chemical toxic substances before
      pregnancy. The pooled OR values of multiple-factor analysis were as follows:
      spiritual stimulus (4.08), exposure to chemical toxic substances (3.54), cold
      with fever (5.00) during pregnancy. CONCLUSION: The main factors influencing the
      incidence of CHD in Chinese people were current spiritual stimulus, exposure to
      chemical toxic substances or pesticides, negative life events during pregnancy,
      cold or fever during early pregnancy, exposure to chemical toxic substances
      before pregnancy.

PMID- 19173944
TI  - [Current situation on primary prevention measures to neural tube defects].

PMID- 19173945
TI  - [Prevalence, clinical and public health significance of occult hepatitis B virus
      infection].

PMID- 19173946
TI  - [Overview of human hereditary susceptibility on tuberculosis].

PMID- 19173947
TI  - [Application of microarray in infections disease diagnosis and epidemiology].

PMID- 19173948
TI  - [A serum-epidemiological study on Anaplasma phagocytophila in the Wuyishan forest
      area in Fujian].

PMID- 19173949
TI  - [Study on the papA and papG genotyping of 45 uropathogenic Escherichia coli
      strains].

PMID- 19173950
TI  - [Clinical epidemiologic analysis of cardiac cancer during the past 30 years (1977
      2006) in Gansu province].

PMID- 19173951
TI  - [Study on the clinical epidemiology of gastric cancer in an area of Tibetans
      plateau].

PMID- 19173952
TI  - [Analysis of pre-treatment screening on 160 HIV/AIDS patients receiving highly
      active antiretroviral therapy ( AZT +3TC + EFV) treatment].

PMID- 19173953
TI  - [Epidemiological characteristics of inpatients induced by injury for a 10 year
      period (1994-2003) in Shenzen, China].

PMID- 19173954
TI  - [An epidemiological survey of acute stress disorder after a violent earthquake in
      Wenchuan].

PMID- 19173955
TI  - [Study on the impact factors of condom usage among the floating population].

PMID- 19173956
TI  - [Study on immunoprotection of varicella vaccine in a elementary school in
      Chaoyang district, Beijing].

PMID- 19173957
TI  - [Investigation on the epidemiology of Far-East tick-borne spotted fever in the
      Northeastern area of China].
AB  - OBJECTIVE: To study the infection rate, epidemiological features of Far-East tick
      borne spotted fever in the Northeastern area of China and to provide evidence for
      prevention and control. METHODS: Nine cities from the three Northeastern
      provinces were chosen. Human serum, rat, serum, free tick sample as well as blood
      from suspected patients were determined by indirect immuno-fluorescence assay.
      Rickettsiae was identified by guinea pigs plant method. RESULTS: The overall rate
      of infection among human beings was 17.46%, with R. heilongjiangensis antibody
      the major one among the nine cities. The annual infection rate was 9.4%. In a two
      year period, the rates of being bitten by ticks among forestry workers was 92.8%,
      and 33.5% among soldiers. The antibody positive rate and tick-bite rate were
      positively correlated. The serum positive rate in rats was 27.3%. 20 strains were
      isolated from blood which confirmed that 16 cases were related to R.
      heilongjiangensis and another 16 cases were Far East tick-borne spotted fever.
      Clinical features of the patients were also analyzed. CONCLUSION: Nine cities
      from the east part of the Northeastern areas of China were confirmed of having R.
      heilongjiangensis infection (3.4% - 27.4%). Our results also demonstrated that in
      those above-mentioned areas, there had been an existing natural foci of Far East
      tick-borne spotted fever.

PMID- 19173958
TI  - [Survival and immune response of rural HIV/AIDS patients after free
      antiretroviral therapy].
AB  - OBJECTIVE: To assess the adherence, immunologic and survival responses in HIV
      infected patients receiving free antiretroviral therapy (ART). METHODS: All adult
      HIV-infected patients in Wenxi county who started antiretroviral treatment (ART)
      between 01 July 2001 and 31 December 2006 and aged above 18 years were included
      in this study. Epidemiological survey and laboratory tests were performed before,
      0.5 months after, 1 months after, 2 months after and every 3 months after
      initiation of ART to recognize the adherence, efficacy (CD(4)(+) T cell counts)
      and survival to the regimens. RESULTS: The median follow-up time period was 16.5
      months (Interquartile: 15.5 - 20.8 months). At baseline, the median of CD(4)(+) T
      cell counts were 154 cells/microl (Interquartile: 81 - 212 cells/microl).
      Treatment was effective in most of the patients, the CD(4)(+) T cell count of
      patients increased after the initiation of ART. The maximum increase was recorded
      at month 3, from the median of 154 cells/microl to 220 cells/microl (P < 0.001),
      and thereafter the count remained stable. When comparing with patients with
      baseline CD(4)(+) T cell count > or = 100 cells/microl, those with baseline
      CD(4)(+) T cell count < 100 cells/microl showed a higher mean increase in the
      first three months of treatment. The cumulative probability rates of remaining
      alive were 0.94, 0.88 and 0.87 at 3, 12, 24 months, respectively. In multivariate
      Cox's proportional hazard models, after adjustment for the type ofinitial
      regimens (NVP vs. EFV/IDV), CD(+)(4) T cell count of less than 50 cells/microl
      (vs. 50 cells/microl or more) was strongly associated with death hazard ratio
      0.21 (95%CI: 0.06 - 0.68). CONCLUSION: Our data showed that ART was effective for
      improving immunologic response of adult patients with HIV/AIDS. CD(4)(+) T cell
      count at initiation was associated with survival time in patients starting ART,
      suggesting that monitoring of CD(4)(+) T count should be strengthened to early
      initiate antiretroviral therapy for HIV-infected patients.

PMID- 19173959
TI  - [Study on the correlation between HIV drug resistance and CD4+ T-lymphocyte of
      AIDS patients under antiretroviral treatment in Henan province].
AB  - OBJECTIVE: To study the correlation between genotype drug resistance and CD(4)(+)
      T-lymphocyte of AIDS patients who received antiretroviral treatment in Henan
      province. METHODS: Several indicators were studied through questionnaires and
      whole blood was collected to analyze CD4+ T-lymphocyte as well as the virus load.
      In-House technique was used to detect the genotype drug resistance. RESULTS:
      32.21% and 29.17% of the patients were identified as genotype drug resistant to
      AIDS when used first and second generation medicine schemes but the improvement
      (P = 0.7538) of disease process was not influenced much. However, if the genotype
      drug resistance of patients with HAART last longer than two years (33.20%) or
      patients with HAART less than one year (18.97%), a greater impact on the
      improvement was noticed. Age (OR = 0.68) and the interval on distribution of
      medicines (OR = 1.93) had a great impact on the improvement with the genotype
      drug resistance through logistic regression analysis. Medicine scheme (OR =
      0.51), genotype drug resistance (OR = 3.20) and the rate of regular dose in a
      month (OR = 0.51) all had a great impact on the improvement to CD4+ T-lymphocyte
      by logistic regression analysis. CONCLUSION: Part of HIV/AIDS patients showed
      resistant to genotype drugs in Henan province, suggesting that we must reinforce
      the surveillance on HAART and program on drug administration to the patients, in
      order to increase the number of CD4+ T-lymphocyte so as to avoid the development
      of drug resistance.

PMID- 19173960
TI  - [Health seeking behavior and related influential factors on rural reproductive
      tract infections among rural women at reproductive age].
AB  - OBJECTIVE: To understand health seeking behavior and its influential factors to
      reproductive tract infections (RTIs) on women at reproductive age in the rural
      areas. METHODS: 54540 fertile women aged 15 - 49 were surveyed by a stratified
      cluster-random sampling method and gynecological examination were conducted in
      two steps: converging at the clinics, and then visiting their households, later,
      31 624 women who had at least one RTI symptom were chosen. RESULTS: Among all the
      women at reproductive age, the rate of having at least one RTI symptom was 59.8%
      with the means of RTI symptom as 1.66 +/- 0.89. 15989 women went to see doctors
      out of the 31 624 women who had RTI symptoms, with a proportion of 50.6%. The
      results of logistic regress showed that those women whose husbands having higher
      education level, higher income, more RTI symptoms and better knowledge on RTI
      were more easily to go to the hospitals. However, those women whose husbands
      working out of the county, having older first bearing age and more numbers of
      pregnancy were less likely to go to the hospitals. Reasons that refrained them
      from going to see a doctor would include: 2137 (13.7%) did not know that RTI was
      a disease; 7443 (47.6%) of them thought that every woman were bound to have at
      least one symptom and it did not matter; 1629 (10.4%) of them felt shameful; 349
      (2.2%) learned that the diseases were incurable; 975 (6.2%) felt the cost of
      treatment was too expensive; 2101 (13.4%) had no time; 1001 (6.4%) would treat
      themselves through buying medicines over the counter. CONCLUSION: RTI symptoms
      were quite prevalent among women at reproductive age but the rate of seeing a
      doctor was low and caused by multi-factors. Health education and gynecological
      census in increasing the curable rate of RTIs should to be strengthened.

PMID- 19173961
TI  - [Study on the reliability, validity and sensitivity of a Family Burden Scale used
      for evaluation on schistosomiasis].
AB  - OBJECTIVE: To evaluate the reliability, validity and sensitivity of a Family
      Burden Scale (FBS) of disease used on schistosomiasis. METHODS: 224
      schistosomiasis patients were investigated, using the FBS. Reliability was
      estimated by Cronbach's alpha coefficient and split-half reliability. Validity
      was tested by factor analysis. Sensitivity was evaluated by comparison of
      patients with different income levels. RESULTS: The Cronbach's alpha coefficient
      was 0.874 and split-half reliability was 0.939 for FBS, respectively. Most values
      of Cronbach's alpha and split-half reliability for each component of scale were
      above 0.70. Construct validity was appraised by factor analysis, and 6 factors
      were identified. These factors could explain 66.76% of the total variance.
      Patients with different income levels showed significant difference in terms of
      family burden for schistosomiasis (P < 0.001). CONCLUSION: This FBS appeared to
      have satisfactory reliability, validity and sensitivity and could be used in
      evaluating family burden of schistosomiasis patients.

PMID- 19173962
TI  - [Reliability and validity of a Short-Form Health Survey Scale (SF-36), Chinese
      version used in an elderly population of Zhejiang province in China].
AB  - OBJECTIVE: To evaluate the validity and reliability of a Chinese version on the
      Short-Form Health Survey Scale (SF-36) among elderly population. METHODS:
      Questionnaire including SF-36 Chinese version was administered in a cross
      sectional study from October to December 2007. 4241 elderly people over 60 years
      old from rural and urban area in Zhejiang province were face-to-face interviewed
      by well-trained investigators, and then analyses on correlation, reliability,
      factors, t-test and one-way ANOVA were made to evaluate on reliability and
      validity of the scale. RESULTS: The SF-36 Chinese version had good split-half
      reliability (r = 0.91, P < 0.001) and all the internal consistency Cronbach's
      alpha coefficients exceeded 0.8 except for VT (alpha = 0.65), SF (alpha = 0.65)
      and MH (alpha = 0.40). The correlative coefficients between each item and its
      domain were all greater than the 0.4 thresholds except item 9 - 2, and they were
      greater than the correlation between the item and other domains for all but item
      9 - 8. These results demonstrated that the SF-36 Chinese version had good
      convergent validity and discriminant validity. The distribution of 35 items in 6
      public factors (the cumulative variance = 67.04%) extracted from them was
      consistent with the basic conceived concept. All domains except MH had good
      validity to discriminate different categories. CONCLUSION: The SF-36 Chinese
      version had good reliability and validity. It was acceptable for the evaluation
      on quality of life in elderly population, but the reliability and validity of MH
      were relative low and the items such as 9 - 2, 9 - 8 in MH and 3 - 1 in PF were
      not suitable for Chinese elderly population.

PMID- 19173963
TI  - [Surveillance and pathogenic analysis on non-typhoidal Salmonella in Guangdong
      province, 2007].
AB  - OBJECTIVE: To understand non-typhoid Salmonella in diarrhea patients from
      Guangdong province in order to timely discover the outbreaks caused by them as
      well as to grasp the serotypes, antibiotic resistance and pulse-field gel
      electrophoresis (PFGE) types of those strains isolated from this surveillance
      program. METHODS: Salmonella strains from diarrhea patients were detected and all
      the positive strains were tested by serum agglutination, antibiotic
      susceptibility and PFGE. RESULTS: 71 non-typhoid Salmonella strains were isolated
      from 1128 stool samples, with a positive rate of 6.29%. All the strains were
      divided into 29 serotypes, with Salmonella serotype enteritidis and typhimurium
      showing the most common serotypes. Most of the strains were sensitive to
      cephalosporins and quinolones. The antibiotic resistance rates of S. typhimurium
      were higher than S. enteritidis and S. stanley. Other than S. enteritidis, all
      the serotype strains did not have the same type of PFGE. 17 S. enteritidis
      strains digested by XbaI were divided to 8 PFGE types while the PFGE 4 type
      appeared the most common one. 12 S. enteritidis strains were typed again by SfiI
      and NotI, and there were still 3 groups of strains showing the same PFGE pattern.
      CONCLUSION: Most of the infection caused by non-typhoidal Salmonella was sporadic
      in Guangdong province in 2007. Cephalosporins and quinolones seemed the best in
      curing the infection of non-typhoidal Salmonella at the clinics.

PMID- 19173964
TI  - [A dynamic analysis on incidence and trend of HIV-1 epidemics among intravenous
      drug users, attendants at the STD clinics and pregnant women in Yunnan province,
      China].
AB  - OBJECTIVE: BED-CEIA assay was used in HIV/AIDS surveillance sentinel sites to
      identify recent HIV-1 infection, to estimate HIV-1 incidence and to understand
      the epidemic trends in Yunnan province. METHODS: Serum specimens were collected
      from IDUs in sentinel sites, attendants in STD clinics and pregnant women under a
      cross sectional study from 2000 to 2007. Specimens confirmed as HIV-1 positive
      were tested with BED-CEIA to find recent HIV-1 infection, then the annual HIV-1
      incidence for each group was calculated and the trends of HIV-1 incidence
      observed. RESULTS: 144 780 serum specimens were collected and 4932 of them were
      confirmed as HIV-1 positive. 4678 positive specimens were tested with BED-CEIA
      and 723 ont of them were identified as recent infections. Specimens from the two
      years were combined for testing. The average HIV-1 prevalence among IDUs was
      18.2% - 26.9% from 2000 to 2007 and the annual incidence were 14.65%, 6.21%,
      4.06%, 2.23% respectively. The average HIV-1 prevalence among attendants in STD
      clinics was 1.6% - 3.2% and the annual incidence rates were 1.46%, 0.76%, 0.52%,
      0.33% respectively. The average HIV-1 prevalence among pregnant women was 0.2% -
      0.5% and the annual incidence rates were 0.16%, 0.11%, 0.10%, 0.09% respectively.
      CONCLUSION: HIV-1 incidence rates among IDUs, STDs and pregnant women showed a
      steady decrease.

PMID- 19173965
TI  - [Estimation of disability weights on malignant neoplasms in Shandong province].
AB  - OBJECTIVE: To determine stage-specific and average disability weights (DWs) of
      malignant neoplasm and provide support and evidence for study on burden of cancer
      and policy development in Shandong province. METHODS: Health status of each
      cancer patient identified during the cancer prevalence survey in Shandong, 2007
      was investigated. In line with the GBD methodology in estimating DWs, the
      disability extent of every case was classified and evaluated according to the Six
      class Disability Classification version and then the stage-specific weights and
      average DWs with their 95% confidence intervals were calculated, using SAS
      software. RESULTS: A total of 11 757 cancer cases were investigated and
      evaluated. DWs of specific stage of therapy, remission, metastasis and terminal
      of all cancers were 0.310, 0.218, 0.450 and 0.653 respectively. The average DW of
      all cancers was 0.317 (95%CI: 0.312 - 0.321). Weights of different stage and
      different cancer varied significantly, while no significant differences were
      found between males and females. DWs were found higher (> 0.4) for liver cancer,
      bone cancer, lymphoma and pancreas cancer. Lower DWs (< 0.3) were found for
      breast cancer, cervix uteri, corpus uteri, ovarian cancer, larynx cancer, mouth
      and oropharynx cancer. CONCLUSION: Stage-specific and average DWs for various
      cancers were estimated based on a large sample size survey. The average DWs of
      0.317 for all cancers indicated that 1/3 healthy year lost for each survived life
      year of them. The difference of DWs between different cancer and stage provide
      scientific evidence for cancer prevention strategy development.

PMID- 19173966
TI  - [Study on molecular epidemiology of Borna disease virus in Zunyi regions of
      Guizhou province].
AB  - OBJECTIVE: In order to study the epidemiology of Borna disease virus (BDV) in
      Zunyi region and its surrounding regions in Guizhou province. METHODS: p24
      fragment of BDV fragments in peripheral blood mononuclear cells (PBMC) from 43
      patients with viral encephalitis (VE), 9 cases with multiple sclerosis (MS), 7
      cases with Guillain-Barre syndrome (GBS), 5 cases with Parkinson disease (PD), 98
      healthy donors and 300 goats were examined by quantitative fluorescence nested
      reverse transcriptase polymerase chain reaction (PCR). Gene sequence and amino
      acid sequence were analyzed for positive products. RESULTS: The positive rate of
      BDV p24 fragment in PBMC from VE (13.95%) and MS (22.22%) were significantly
      higher than in healthy donors (0%, P < 0.05). The positive rate of BDV p24
      fragment in PBMC from goats was 0.67%, without statistical difference when
      compared with healthy donors (P > 0.05). Guillain-Barre syndrome and Parkinson
      disease (PD) were tested negative. The sequence of the BDV p24 fragment from the
      patients with VE was in conformity with that of the MS. Results presented that 3
      situs consistency silent mutation when compared with strain V and its homogeneity
      was 96.51%. 2 situs consistency silent mutation compared with BDV/MDCK and its
      homogeneity was 97.67%. 2 situs consistency silent mutation when compared with
      C6BV and its homogeneity was 97.67%. Sequences of the BDV p24 fragment from the
      goats presented 3 situs consistency silent mutation when compared with strain V
      and its homogeneity was 96.51%. 3 situs consistency silent mutation when compared
      with BDV/MDCK and its homogeneity was 96.51%. 3 situs consistency silent mutation
      when compared with C6BV and its homogeneity was 96.51%. However, there were no
      changes of encoding amino acids in all BDV p24 fragments from neuropsychiatric
      disorders. CONCLUSION: Our data indicated that the BDV infection was presented in
      patients with VE, MS and goats from Zunyi region and its surrounding regions of
      Guizhou province. BDV might play a potential role in the development of VE, MS as
      well as having correlations with animals.

PMID- 19173967
TI  - [Detection of co-infection with Lyme spirochetes and Spotted fever group
      rickettsiae in a group of Haemaphysalis longicornis].
AB  - OBJECTIVE: The present study was conducted to investigate the infection of Lyme
      disease, Spotted fever, Ehrlichiosis (anaplasmosisin) in wild animals and ticks
      in the mountain areas of Zhejiang province. METHODS: Nested polymerase chain
      reaction was used to amplify specific DNA sequences of Lyme spirochetes, Spotted
      fever group rickettsiae, Ehrlichia(anaplasma) from samples of mice and ticks.
      RESULTS: 14 positive samples were identified from 121 mice and 105 groups of
      ticks. Among mice samples, one positive 5S-23S rDNA intergenic spacer of Borrelia
      burgdorferi and two 5' fragments of Ehrlichia (anaplasma) 16S rDNA were obtained.
      11 positive results were detected from tick samples including three 5S-23S rDNA
      intergenic spacer regions of Borrelia burgdorferi and eight 5' fragments of
      Spotted fever group rickettsiae outer member protein A gene. One group of adult
      ticks, Haemaphysalis longicornis, which had been collected from eastern mountain
      area were detected to have co-infected with Lyme spirochetes and Spotted fever
      group rickettsiae. The positive sequences of 5S-23S rDNA intergenic spacer and
      ompA gene were tested and analyzed as Lyme spirochetes while rickettsia which was
      closely related to Borrelia valaisiana and R. massiliae. CONCLUSION: This was the
      first report about co-infection of Lyme spirochetes and Spotted fever group
      rickettsiae found in the same group of adult Haemaphysalis longicornis. It is
      very important to strengthen the surveillance program on tick-borne infectious
      disease and their pathogenic in vectors, wild animals and targeted high risk
      groups and to differentiate the clinical manifestation and diagnosis to extend
      the knowledge of tick-borne infectious diseases in Zhejiang.

PMID- 19173968
TI  - [Application of purified recombinant outer membrane lipoprotein LipL32 in
      detecting antibodies among leptospirosis cases].
AB  - OBJECTIVE: To establish recombinant outer membrane lipoprotein LipL32-based
      antibody detection assays in identifying leptospirosis. METHODS: Recombinant
      leptospiral outer membrane protein LipL32 was obtained by genetic engineering
      method. This purified protein was used in the indirect and sandwich ELISA assays
      to test the antibodies in sera of human beings and rats, and the results were
      compared with those obtained by microscopy agglutination test (MAT) and imported
      ELISA kit. RESULTS: When the acute and convalescent phase specimens from 9
      leptospiral patients were tested, the detected rates of three ELISAs were similar
      to the MAT. Among the 45 probable cases which MAT showed positive, 32 (71.11%)
      samples were positive by r32-I-ELISA, 36 (80.00%) by r32-S-ELISA, while 28.89%
      (13/45) samples were positive and 55.56% (25/45) were suspicious by D.A.I-ELISA.
      The specificity of r32-I-ELISA and r32-S-ELISA were 97.10% (67/69) for 69
      specimens. 43 healthy specimens were negative by both r32-I-ELISA and r32-S
      ELISA, 14 healthy specimens were negative by D.A.I-ELISA. Among 16 non
      leptospirosis patients, two specimens were positive by r32-I-ELISA and r32-S
      ELISA, D.A.I-ELISA and identified one positive specimen, while 12 specimens were
      suspicious by D.A.I-ELISA. For 10 syphilis specimens, data obtained through three
      ELISAs were in consistent with that by MAT. A sandwiched ELISA, using rLipL32
      protein as the antigen was developed to detect rat sera. Considering MAT as
      standard test, the sensitivity and specificity were 86.75% (131/151), 99.19%
      (122/123) respectively with coincidence rate as 92.34% (253/274). CONCLUSION: The
      recombinant protein LipL32 had high immunoreactivity and could be used as an
      antigen for the detection of pathogenic leptospirosis. In summary, the novel
      sandwiched ELISA with rLipL32 showed similar sensitivity and specificity to that
      of MAT in the antibody detection of rat leptospirosis. It was suitable for large
      scales field sero-epidemiological studies.

PMID- 19173969
TI  - [Isolation, identification and 16S rDNA phylogenetic analysis of Klebsiella
      pneumonia from diarrhea specimens].
AB  - OBJECTIVE: To understand the biochemical characteristics and 16S rDNA genetic
      sequence evolution of strains isolated from diarrhea specimens so as to provide
      basis for classification and identification of Klebsiella pneumoniae. METHODS:
      Specimens were cultured using MacConkey and SS medium. All isolates were
      identified as K. pneumoniae by automated biochemical tests. DNA was extracted,
      1500 bp fragments of the 16S rDNA gene were by amplified PCR and sequenced with
      K. pneumoniae 16S rDNA primer, after being cut. Fragments of 1000 bp overlapping
      sequences were analyzed by Blast to confirm the identity of the isolates. A
      phylogenetic tree was constructed by PHYLIP process to analyze the 16S rDNA
      sequence of the isolated strain with other relative bacteria species in the
      GenBank databases. RESULTS: Among 113 specimens of infectious diarrhea, 25 K.
      pneumoniae strains were identified by biochemical tests, of which 21 subsp.
      pneumoniae and 4 subsp. ozaenae, no subsp. of rhinoscleroma were isolated.
      Strains of subsp. pneumoniae were found having nature of resistance. All isolates
      were resistant to penicillin G and susceptible to polymyxin with some strains
      were resistant to Nitrofurantoin, Cephalothin, Kanamycin, Tobramycin. After
      searching in GenBank of 16S rDNA, strains biochemical identified as subsp.
      ozaenae shared high similarity with Salmonella strains and other intestinal
      bacteria. 16S rDNA phylogenetic analysis could be used to confirm subsp.
      pneumoniae, but could not separate other subspecies of K. pneumoniae completely.
      CONCLUSION: 16S rDNA phylogenetic analysis useful in identifying and classifying
      K. pneumoniae.

PMID- 19173971
TI  - [Establishment of a nested PCR to identify hepatitis B virus genotypes A-D and
      subgenotypes B1, B2, C1 and C2].
AB  - OBJECTIVE: To establish a hepatitis B virus (HBV) nested PCR (nPCR) for detection
      of genotypes A-D and subgenotypes B1, B2, C1 and C2. METHODS: The entire HBV
      nucleotide sequences of genotypes A-H retrieved from GenBank were compared and
      analyzed by DNAStar software. The PCR primers were designed by Primer Premier 5.0
      software, and the nPCR for genotyping HBV/A-D as well as subgenotyping B1, B2, C1
      and C2 were established. There were 3 steps in the process:step 1 for genotypes
      B, D and subgenotypes C1, C2 with the amplification of Mix A; step 2 for genotype
      A with the amplification of Mix B; step 3 for subgenotypes B1 and B2 with the
      amplification of Mix C in the second-round PCR, based on the first-round
      amplification procedure. A total of 68 serum samples from patients with chronic
      HBV infection were detected by nPCR. 15 of 68 sera were selected randomly and
      their PCR products were directly sequenced to confirm the accuracy of the method.
      RESULTS: Among 68 serum samples of patients with chronic HBV infection detected
      by the nPCR, 23.53% (16/68) were infected with B2, 11.76% (8/68) with C1, 48.53%
      (33/68) with C2, 1.47% (1/68) with D, 11.76% (8/68) with B2C2 mix strains, 1.47%
      (1/68) with C2D mix strains and 1.47% (1/68) with B2/C1/D mix strains. The
      sequencing analysis of the 15 serum samples had the same results as detected by
      nPCR. CONCLUSION: nPCR is a simple, rapid method and able to detect genotypes A-D
      and subgenotypes B1, B2, C1 and C2 subtypes of HBV with both high sensitivity and
      specificity.

PMID- 19173970
TI  - [Molecular typing of methicillin-resistant Staphylococcus aureus isolated from
      hospitalized patients in Qingdao].
AB  - OBJECTIVE: To explore the molecular types of methicillin-resistant Staphylococcus
      aureus (MRSA) strains present in major hospitals in Qingdao area, using pulsed
      field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) methods,
      trying to find out the epidemiological characteristics of these MRSA isolates.
      Correlation of the PFGE types with microbiological phenotypes and clinical data
      was also studied. METHODS: 360 isolates of MRSA were procured during 2003 to 2007
      from major hospitals in Qingdao. PFGE technology was applied to comparatively
      analyze the chromosomal DNA digested with endonuclease SmaI. Comparison of DNA
      fragments patterns from each MRSA strain and cluster analysis were performed with
      the Bionumerics version '2.0' software. A dendrogram was generated using PFGE
      macrorestriction fragments on gel images. Data was used to predict the
      possibility of each PFGE type via SPSS software version 11.0, using the variables
      as predictors including groups on patient's age, gender, source and the site
      where MRSA was isolated. Antibiotic sensitivity patterns of these MRSA isolates
      were determined by K-B tests, and a correlation between these patterns and PFGE
      types was investigated. Housekeeping genes were amplified with PCR and sequenced
      in representative strains of variant PFGE types to identify their allelic
      profile. RESULTS: 5 types of PFGE patterns (M0-M4) were identified with M1 being
      the predominant and M2 next to it which was significantly correlated to the
      isolates from wounds. M3 type strains were mainly isolated from ICU wards and
      there were a few cases complied with M4 type with no correlated variant factors
      found in this study. A unique pattern of MRSA isolates with its M0 distinct from
      other types had not been reported. No significant association was found between
      PFGE individual types, gender or age groups. M1 and M2 types were the major
      proportional PFGE patterns among different hospitals. No vancomycin-resistant
      isolates were detected among 360 MRSA strains. No significant association was
      found between individual antibiotic resistance and specific PFGE types. Data from
      MLST analysis showed that the allelic profiles of M1 and M3 type strain had the
      same ST239 linage which was commonly present in China. For M2 and M4
      representative strains, the allelic profiles were ST5 and ST240, respectively.
      ST45 and ST398 were corresponding to two PFGE patterns clustered as M0 type.
      CONCLUSION: Nosocomial infection due to MRSA was evenly distributed among
      different age groups and no gender bias was observed. The PFGE types of MRSA
      strains isolated in major hospitals in Qingdao were highly correlated with the
      sources of isolates and ST239 isolate seemed the prevalent and widespread one.
      Strategies should be designed to further monitor and prevent or minimize the
      spread of ST5 MRSA isolates and the like, in Qingdao area.

PMID- 19173972
TI  - [Evaluation of multiplex nucleic acid testing assays for screening of hepatitis B
      virus DNA in blood donation process].
AB  - OBJECTIVE: To evaluate the multiplex nucleic acid testing (NAT) assays for HBV,
      HCV and HIV in detecting HBV DNA in plasma samples. METHODS: 534 plasma samples
      collected form several areas were detected with Abbott Architect i2000 HBsAg, ani
      HBs, HBeAg, anti-HBe, anti-HBc and anti-HBc IgM diagnostic kits. HBV DNA levels
      of those samples were detected with Roche COBAS AmpliPrep/COBAS TaqMan HBV Test.
      Two kinds of multiplex NAT assays for HBV, HCV and HIV were used to test HBV DNA
      of those 534 samples. Results of serology-markers and quantitative HBV DNA levels
      with results of NAT were compared. RESULTS: HBV DNA was positive in all 81 HBsAg,
      HBeAg and anti-HBc positive samples, detected by both of NAT assays. HBV DNA was
      positive in 11 and 19 of 200 HBsAg negative samples when detected with the two
      kinds of NAT assays separately. Compared with the quantitative results detected
      by Roche COBAS AmpliPrep/COBAS TaqMan HBV Test, the HBV DNA positive rates were
      96.9% and 94.3% in 193 samples of HBV DNA levels over 500 IU/ml while 40.2% and
      45.3% in 117 samples of HBV DNA levels below 500 IU/ml while 99.3% and 96.0% in
      151 samples of DNA negative HBV. CONCLUSION: There are some occult low level HBV
      DNA carriers with HBsAg negative results in China. NAT assays for HBV, HCV and
      HIV may be useful to improve the transfusion safety.

PMID- 19173973
TI  - [Evaluation on HBeAg conversion time when treating chronic hepatitis B patients
      with combination of lamivudine and traditional Chinese medicine].
AB  - OBJECTIVE: To evaluate the effect of the combined use of traditional Chinese
      medicine and lamivudine (LMD) in treating chronic hepatitis B patients, and to
      follow the serological response for six months or longer. METHODS: CNKI, Wanfang
      data, VIP data, CBMdisk, MEDLINE, EMBASE, BIOSIS and Cochrane Central Register of
      Controlled Trials database and literature were searched, to include randomized
      controlled trails (RCT) that used LMD alone or combined with traditional Chinese
      medicine. RevMan 4.2 was used for data analysis. RESULTS: The Meta analysis of 7
      trails demonstrated that the HBeAg conversion rate in treatment group was higher
      than those from the control group, and the differences were statistically
      significant at 6, 9, 12 months. CONCLUSION: Data demonstrated that early
      intervention of traditional Chinese medicine might increase the HBeAg conversion
      rate but conclusion needs to be more specific to the types of trials.

PMID- 19173974
TI  - [Using a method--'floating absolute risks' to estimate the confidential intervals
      of relative hazards].
AB  - Compare the risks between multiple groups and to avoid bias, using arbitrary
      reference group. Floating absolute risks (FAR) is used to estimate the relative
      hazard ratios and to get the confidence intervals. From the example, FAR can
      describe the construction of standard error for all groups. It gets the relative
      hazard ratios and 95% confidence intervals between any two groups; even if
      neither is used as baseline data. FAR can eliminate the bias in comparison of any
      two groups by selecting a baseline group. It is useful in many epidemiological
      studies.

PMID- 19173975
TI  - [Risk prediction model of perinatal congenital heart disease].
AB  - Through analyzing the influencing factors of congenital heart disease (CHD), it
      is aimed to establish CHD risk prediction model in fetus, and simultaneously
      provide theoretical foundation for CHD prevention. One-factor logistic regression
      method was used to screen the significant factors regarding CHD, and to
      separately adopt multiple-factor non-conditional logistic regression method and
      decision tree to set up model prediction fetus CHD risk and to analyze the
      advantages and shortcomings. Correct classification rates turned to be 80.93% and
      82.79% respectively among 215 'training samples' by the two methods and the rates
      were 85.45% and 89.09% respectively among 55 'testing samples'. The alliance of
      logistic regression and decision tree can overcome influence by co-linearity to
      guarantee the accuracy and perfection, as well as promoting the predictive
      accuracy.

PMID- 19173976
TI  - [Application of 'Family-Based Association Test' in studying genetic
      epidemiology].
AB  - To introduce the application of Family-Based Association Test (FBAT) in detecting
      the association or linkage between marker alleles and phenotype or traits in
      genetic epidemiology. A brief overview on basic steps involved in design,
      implementation, principles of application, available software as well as the use
      and feature of FBAT method, were explained based on data from nuclear family.
      Advantages of FBAT were compared to conventional genetic statistics approaches.
      Data showed that this approach might make the most use of parental genotype,
      genotype of affected offspring and their phenotype to test the association
      between biallelic or multi-allelic markers, phenotype or traits to their
      conditional distributions given the minimal sufficient statistics under the null
      hypothesis for the genetic model. Covariates, such as traits or environmental
      exposures, might be included into this procedure so as to effectively control the
      bias of population admixture through adjustment of variables. FBAT could be used
      for genetic analysis with data from nuclear family since it is more advantageous
      than the conventional statistical methods.

PMID- 19173977
TI  - [Suicidal behavior among people living with HIV/AIDS, a review].

PMID- 19173978
TI  - [The impact of great earthquakes on population health].

PMID- 19173979
TI  - [Progress on the molecular typing of Streptococcus suis].

PMID- 19173980
TI  - [Isolation and Identification of Borrelia burgdorferi sensu lato in Leye county,
      Guangxi province].

PMID- 19173981
TI  - [Analysis on the reported cases of infectious diseases and correlative things in
      rural clinic Tianjin in 2007].

PMID- 19173982
TI  - [Analysis on seat-belt wearing behavior about the occupants in small size motor
      vehicles in 5 districts, Zhejiang province].

PMID- 19173983
TI  - [Research on the relationship between areas with high prevalence of birth defects
      and earth elements].

PMID- 19173984
TI  - [Survey on drinking while driving behavior in the cities of Nanning and Liuzhou,
      Guangxi province].

PMID- 19173985
TI  - [Methods of cervical cancer screening and facing new problems in China].

PMID- 19173987
TI  - [Screening for differential methylation status by CpG island microarray in the
      hepatocellular carcinoma cell lines].
AB  - OBJECTIVE: To profile the methylation alterations of CpG islands in
      hetpatocellular carcinoma cell lines. METHODS: A global analysis of DNA
      methylation using the Human CpG-island 12K Array (HCGI12K) from Canada University
      Health Network was performed on nine human hepatocellular carcinoma (HCC) cell
      lines (Hep3B, HepG2, PLC/RPF/5/RPF/5, SMMC-7721, BEL-7402, MHCC97-H, MHCC97-L,
      HCCLM3, HCCLM6) and a control cell line Chang's liver. Metastatic potential
      related alterations were also screened in MHCC97 series cell lines (MHCC97-H,
      MHCC97-L, HCCLM3, HCCLM6), using MHCC97-L, a cell line with low metastatic
      potential, as control. To screen the key genes which are hypermethylation or
      hypomethylation in the HCC cell lines compared with the normal liver cell line by
      normalization processing and cluster analysis of microarray data. Two randomly
      selected genes was analyzed by methylation specific PCR to verify the chip
      results. RESULTS: By a standard of methylation alteration ratio > or = 2 or < or
      = 0.5, fifty-eight CpG island cloning sites and sixty-six upstream or downstream
      tumor-related genes were identified. The genes were oncogenes, tumour suppressor
      genes and their ligand genes, apoptosis-related genes, cell proliferation and
      differentiation genes, cell cycle-related gene and cell signaling pathway key
      genes such as Wnt, ras, and FGF pathway-related genes. The methylation specific
      PCR results were consistent with those obtained by chips. CONCLUSION: The results
      of this study demonstrate that there are a series of CpG island methylation
      alterations in HCC cell lines. The expression of many oncogenes, tumor suppressor
      genes and other key genes may be up- or down-regulated, respectively, because of
      their CpG island hypomethylation or hypermethylation accordingly. It may provide
      a basis for screening HCC biological markers by CpG island methylation
      profilling.

PMID- 19173986
TI  - [Establishment of a highly-metastatic model of human primary melanoma of the
      small intestine orthotopically transplanted in the small intestine of nude mice].
AB  - OBJECTIVE: To provide an useful animal model for exploring metastatic biology and
      anti-metastatic therapy of primary malignant melanoma of the small intestine.
      METHODS: A 49-year old male patient with malignant melanoma was treated by
      surgery, and the primary tumor in the small intestine and a metastatic tumor in
      the liver were removed. The diagnosis of malignant melanoma was confirmed by
      histopathology. Fresh melanoma tissue fragments taken from the primary intestinal
      tumor and hepatic metastatic tumor were orthotopically implanted into the mucosal
      layer of small intestine in nude mice, respectively. The tumor growth rate,
      invasion and metastasis of the transplanted tumors were observed. Light and
      electron microscopy, immunophenotype analysis, flow cytometry and karyotype
      analysis were carried out. RESULTS: Fragments of the primary and liver metastatic
      malignant melanoma were successfully implanted in nude mice. After continuous
      passages in nude mice, an highly-metastatic model of human primary malignant
      melanoma of the small intestine (from the primary lesion) in nude mice (termed
      HSIM-0602) and a liver metastatic model of human primary malignant melanoma of
      the small intestine (originally from the liver metastatic lesion) in nude mice
      (termed HSIM-0603) were successfully established. Histological examination of the
      transplanted tumors revealed a high-grade melanoma of the small intestine.
      Immunohistochemical stainings of S-100 protein and HMB45 were positive. Many
      scattered melanosomes and melanin complex were seen in the cytoplasm of tumor
      cells. Chromosomal modal number was between 55 and 59. DNA index (DI) was 1.59 -
      1.71, representing a heteroploid. The HSIM-0602 and HSIM-0603 tumor models had
      been maintained for 21 and 23 passages in nude mice, respectively. 227 nude mice
      were used for transplantation. Both the growth rate after transplantation and
      resuscitation rate from liquid nitrogen cryopreservation were 100%. The HSIM-0602
      model exhibited 84.8% lung metastasis, 65.7% liver metastasis and 63.8% lymph
      node metastasis. However, HSIM-0603 displayed 100% liver metastasis, 46.7% lung
      metastasis and 71.3% lymph node metastasis. The transplanted tumors actively and
      invasively grew in the small intestine of nude mice and showed hematogenous and
      lymphatic metastases. CONCLUSION: To our knowledge it is the first time that two
      strains of spontaneous highly-metastatic nude-mouse model of human primary
      malignant melanoma of the small intestine have been successfully established in
      our department. The models are very closely mimic the natural clinicopathologic
      course of primary small intestinal melanoma in humans and provide ideal animal
      models for the researches on metastasis biology and anti-metastatic experimental
      therapy of malignant melanoma of the small intestine.

PMID- 19173988
TI  - [In vivo effect of annexin I down-regulation on the growth of human pancreatic
      cancer in nude mice].
AB  - OBJECTIVE: To further explore the effect of annexin I on the tumor growth of
      human pancreatic cancer in nude mice. METHODS: To knock down the expression of
      annexin I in pancreatic carcinoma cells by RNAi. A nude mouse model of human
      pancreatic cancer was established by subcutaneous inoculation of human pancreatic
      cancer cell line Suit-II cells. The effect of annexin I on tumor growth was
      assessed by tumor growth curve and tumor weight records, and Westen blot and flow
      cytometry were used to examine the expression of annexin I after annexin I
      knocking down. RESULTS: The results of Western blot revealed that the expression
      of annexin I was significantly decreased in Suit-II cells transfected with
      pSilencer-annexin I-siRNA1, and almost completely inhibited in the cells
      transfected with pSilencer-annexin I-siRNA2 and pSilencer-annexin I-siRNA3. The
      growth of tumors transfected with annexin I-siRNA2 and annexin I-siRNA3 was
      inhibited by 76.6% and 68.4%, respectively, in comparison with that of tumor from
      the parent Suit-II cells. At 44 days after tumor cell inoculation, the tumor
      weight was 0.8987 g (transfected with annexin I-siRNA2) and 0.8992 g (transfected
      with annexin I-siRNA3), significantly lower (P < 0.001) than that of tumor from
      parent Suit-II cells (2.5866 g) and transfected with annexin I-siRNAN (2.4070 g).
      CONCLUSION: annexin I promotes the growth and proliferation of pancreatic
      carcinoma cells in vivo and increases the ability of tumor formation in nude
      mice. The results of this study support that annexin I may become a potential
      target in gene therapy for this disease.

PMID- 19173989
TI  - [FTIR spectroscopic explorations of freshly resected laryngeal carcinoma
      tissues].
AB  - OBJECTIVE: To investigate the characteristics of freshly resected laryngeal
      carcinoma by Fourier transform infrared spectroscopy (FTIR). METHODS: FTIR was
      applied to the study of the cancerous tissues and adjacent normal tissues in 32
      patients. RESULTS: Compared with pathological diagnosis results, one benign
      specimen was classified as a malignant, the accuracy was 98.4%. Significant
      differences were seen in the FTIR spectra between the normal and malignant
      laryngeal tissues. The peak at 1085 cm(-1) shift to 1114 cm(-1) showed that the
      relative contents of DNA in laryngeal carcinoma cells was increased. The peak at
      1397 cm(-1) was stronger than 1451 cm(-1) in normal tissues, while it was not
      obvious in cancer tissues. I(2926)/I(2870) in carcinoma cells was lower than that
      in normal tissues. The wave numbers of the bands of amide I and amide II,
      symmetric and asymmetric stretching bands of CH(3), stretching vibration bands of
      C-OH and NH band were shifted to higher number in cancer tissues. CONCLUSION: The
      study shows that the malignant and normal laryngeal tissues have different FTIR
      spectra, which are mainly due to changes in protein, nucleic acid and
      phospholipids. FTIR may become a new method for the diagnosis of laryngeal
      carcinoma in clinical practice.

PMID- 19173990
TI  - [Expression and clinical relevance of ARHI, STAT3 and E2F1 in ovarian serous
      carcinoma].
AB  - OBJECTIVE: To investigate the variation in expression of ARHI, STAT3 and E2F1 and
      the correlation among them during carcinogenesis of ovarian serous carcinoma.
      METHODS: Immunohistochemical staining was used to detect the expression of ARHI,
      STAT3 and E2F1 in samples of 25 normal ovaries, 35 ovarian serous cystadenomas,
      18 borderline serous cystadenomas and 56 ovarian serous carcinomas. The variation
      in expression of the three genes and relationship among them were analyzed.
      RESULTS: ARHI expression was detected in 22 of 25 (88.0%) normal ovaries and 30
      of 35 (85.7%) cystadenomas, but only in 10 of 18 (55.6%) borderline serous
      cystadenomas and 22 of 56 (39.3%) ovarian serous carcinomas, significantly lower
      than that in the normal ovaries and ovarian serous cystadenomas (P < 0.05). STAT3
      expression was found in 14 of 18 (77.8%) borderline serous cystadenomas and 49 of
      56 (87.5%) ovarian serous carcinomas, significantly higher than that in the
      normal ovaries and ovarian serous cystadenomas (P < 0.05). To compare with E2F1
      expression in the normal ovaries, serous cystadenomas and borderline serous
      cystadenomas, E2F1 expression in 46 of 56 (82.1%) ovarian serous carcinomas was
      significantly higher (P < 0.05). It was found that the expression of ARHI was
      inversely correlated with that of STAT3 and E2F1. CONCLUSION: Our findings
      indicate that ARHI expression is down-regulated, but STAT3 and E2F1 expressions
      are up-regulated, with an inverse correlation between ARHI and STAT3 in the
      carcinogenesis of ovarian serous carcinoma.

PMID- 19173991
TI  - [Application of SELDI-TOF-MS in detection of liver metastasis from colorectal
      cancer].
AB  - OBJECTIVE: To establish a serum protein fingerprint model for prediction of liver
      metastasis from colorectal cancer by SELDI-TOF-MS analysis, and to determine the
      differentiatial proteins associated with the metastatic liver cancers. METHODS:
      Data were collected from the Department of General Surgery in Zhongshan Hospital.
      A group of patients with colorectal cancer (CRC) without liver metastasis (n =
      36) and another group with liver metastasis (n = 36) were included in this study.
      Serum samples were collected from peripheral venous blood before operation.
      Special serum protein or peptide fingerprint was determined by surface-enhanced
      laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The
      obtained data were analyzed by Biomarker Wizard software to screen the serum
      protein markers discriminating colorectal cancer patients with and without liver
      metastasis. A serum protein fingerprint model was established. This model was
      blindly verified in of CRC patients with and 44 cases without liver metastasis.
      RESULTS: Comparing the characteristic proteins in those two groups of patients,
      10 specific protein peaks were identified with statistical significance (P <
      0.05). According to m/z growing from small to large, they were: 2398, 2814, 4084,
      4289, 4465, 6422, 6619, 11 482, 11 649 and 13 714. The predictive model had a
      sensitivity of 91.7% and a specificity of 97.2%. The validation showed a
      sensitivity of 75.0% and a specificity of 81.8%. CONCLUSION: A predictive model
      based on differentiatial serum protein fingerprint with high sensitivity and
      specificity has been successfully established. It should be a very useful tool in
      detection and diagnosis of liver metastasis in colorectal cancer patients.

PMID- 19173992
TI  - [Comparison between pathological findings and MR diffusion-weighted imaging in
      primary hepatocellular carcinoma after transcatheter arterial chemoembolization].
AB  - OBJECTIVE: To explore the pathological basis of diffusion-weighted imaging (DWI)
      findings in hepatocellular carcinoma (HCC) after transcatheter arterial
      chemoembolization (TACE). METHODS: DWI was performed in 15 patients with HCC
      treated by TACE within 24 - 48 hours before II-phase operation. The DWI findings
      of the liver lesions were analyzed and correlated with pathological findings
      including macroscopic observation, HE staining and immunohistochemical staining
      for bFGF. RESULTS: (1) The viable tumor area showed mostly hypersignal intensity
      (12/15), whereas coagulative necrotic lesions showed hyposignal (8/15) or
      isosignal intensity (6/15). The ADC values of zones of viable tumor and necrosis
      in tumor were (1.42 +/- 0.16) x 10(-3) mm(2)/s and (1.58 +/- 0.18) x 10(-3)
      mm(2)/s, respectively. There was a significant difference of ADC values between
      the two zones (t = 2.618, P < 0.05). (2) There was a significant difference in
      ADC values of viable tumor between well and poorly differentiated tumors (t = 
      2.646, P < 0.05). The distinction of ADC values of the whole tumor was
      significant among tumors with different degree of necrosis (chi(2) = 7.236, P <
      0.05). (3) A negative correlation was observed between bFGF protein expression
      index and ADC values of viable parts of the tumors in the study group (r = 
      0.552, P = 0.033). CONCLUSION: DWI shows certain characteristic features of the
      HCC after TACE, and can be used to distinguish viable and necrotic tumor tissues
      in HCC after TACE.

PMID- 19173993
TI  - [Clinicopathological characteristics and prognostic factors of breast cancer with
      estrogen- and progesterone-receptor negative and HER-2 overexpression].
AB  - OBJECTIVE: To evaluate the clinicopathological characteristics and prognosis of
      breast cancer with estrogen- and progesterone-receptor negative (ER-/PR-) and HER
      2 overexpression (HER+++) in a Chinese population. METHODS: The data of patients
      with ER-/PR- and HER+++ breast cancer treated in our hospital from March 1999 to
      December 2004 were retrospectively reviewed. The influence of clinicopathological
      characteristics and molecular markers on the survival was analyzed. RESULTS: A
      total of 111 breast cancer patients with ER and PR negative but HER+++ were
      identified, accounting for 4.9% of all the breast cancer patients treated during
      the same period. There were 25 cases (22.5%) in stage I, 44 (39.6%) in stage II
      and 36 (32.4%) in stage III, respectively, with a median age of 49 years.
      Axillary lymph node metastasis was found in 54 cases. The 5-year disease free
      survival (DFS) and overall survival rates (OS) were 70.7% and 73.1%,
      respectively. Univariate analysis showed that lymph node status, primary tumor
      size and pathological stage were prognosis-related factors influencing the DFS
      and OS. However, by multivariate analysis, only primary tumor size and lymph node
      status were independent factors influencing survival. CONCLUSION: The breast
      cancer with estrogen- and progesterone-receptor negative but HER-2 overexpression
      is a particular subtype of breast cancers, with unfavorable clinicopathological
      characteristics and poor survival. Lymph node status and primary tumor size are
      two independent prognostic factors.

PMID- 19173994
TI  - [Cox proportional hazard model analysis of prognosis in patients with carcinoma
      of esophagus and gastric cardia after radical resection].
AB  - OBJECTIVE: To investigate the factors affecting the long-term survival of
      patients with carcinoma of esophagus and gastric cardia after curative resection.
      METHODS: The clinical data of 906 patients with carcinoma of esophagus and
      gastric cardia treated by radical resection in 1996 - 2004 were analyzed
      retrospectively. Twelve clinicopathological factors possibly influencing survival
      were encoded and assessed by Cox regression analysis. RESULTS: The 1-, 3- and 5
      year cumulative survival rates were 89.8%, 75.4% and 71.7%, respectively. The
      univariate analysis showed that age, length of tumor, pathological
      differentiation, number of metastatic lymph nodes, depth of invasion, involvement
      of adjacent organs and the TNM stage influenced the prognosis significantly (P <
      0.01). However, multivariate analysis showed that pathologic differentiation,
      number of metastatic lymph nodes, involvement of adjacent organs and TNM stage
      were independent prognostic factors (P < 0.05). CONCLUSION: The independent
      prognostic factors of the patients with carcinoma of esophagus and gastric cardia
      are pathologic differentiation, TNM stage, number of metastatic lymph nodes, and
      involvement of adjacent organs. The other factors influencing survival are age,
      length of tumor and depth of invasion. Furthermore, invasion of adjacent organs
      suggests worse prognosis, and should be followed-up closely.

PMID- 19173995
TI  - [Clinical analysis of 81 cases with primary small cell carcinoma of the
      esophagus].
AB  - OBJECTIVE: To evaluate the clinical characteristics, treatment and prognostic
      factors in patients with primary small cell carcinoma (SmCC) of the esophagus.
      METHODS: Eighty-one esophageal SmCC patients were treated from 1999 to 2007 in
      our department, and their clinical data were retrospectively reviewed. RESULTS:
      Of the 81 patients, 52 (64.2%) were in limited stage (LS) and 23 (28.4%) in
      extensive stage (ES). The 1-, 3- and 5-year survival rates were 55.6%, 6.2% and
      2.5%, respectively, with a median survival time of 13.5 months for the whole
      group; 69.2%, 7.3% and 3.6%, respectively, with a median survival time of 15
      months for the LS group; while only 25.2%, 0 and 0, respectively, with a median
      survival time of 6 months for the ES group. Multivariate analysis showed that
      disease stage, performance status, multidisciplinary comprehensive therapy and
      mode of treatment were independent prognostic factors. CONCLUSION: Esophageal
      small cell carcinoma is a rare but highly aggressive malignant tumor. Disease
      stage and performance status are important prognostic factors. Appropriate
      treatment may play a key role in improving the survival of the patients.

PMID- 19173996
TI  - [Detection of serum CK19-2G2 and Cyfra21-1 protein and comparison of their
      diagnostic value for lung cancer].
AB  - OBJECTIVE: To evaluate and compare the value of serum CK19-2G2 and Cyfra21-1 in
      diagnosis of lung cancer. METHODS: The serum concentration of CK19-2G2 and
      Cyfra21-1 was detected in 104 patients with lung cancer, 71 with benign lung
      diseases and 105 healthy volunteers. The value of the two parameters in the
      diagnosis of lung cancer was evaluated with ROC curve analysis. The mean level of
      CK19-2G2 in the three groups was compared with that of Cyfra21-1 by Mann-Whitney
      U test, and the correlation between these two parameters was calculated using
      Pearson coefficient correlation test. RESULTS: The mean serum CK19-2G2
      concentration in the lung cancer group was 2.87 mU/ml, significantly higher than
      that in the group with benign lung diseases (1.02 mU/ml) and healthy volunteer
      group (0.01 mU/ml) (P = 0.000). The serum concentration of CK19-2G2 was
      positively correlated with that of Cyfra21-1, with a Pearson coefficient
      correlation of 0.543. Furthermore, the mean serum CK19-2G2 level in squamous cell
      carcinoma group (8.35 mU/ml) was significantly higher than that in the other
      pathologic groups (P < 0.05). CONCLUSION: CK19-2G2, with a higher specificity,
      may be a better tumor marker than CK19-2G2 in respect of specificity for non
      small cell lung cancer (NSCLC), especially for squamous lung carcinoma, and
      deserves further study.

PMID- 19173997
TI  - [The role of (18)F-FDG DHC SPECT-CT in the diagnosis and staging for lung
      cancer].
AB  - OBJECTIVE: To investigate and compare the clinical significance of (18)F-FDG
      single-photon emission computed tomography and computed tomography (SPECT-CT) in
      the diagnosis and staging of lung cancer. METHODS: From July 2005 to July 2007,
      71 patients with suspected lung cancer received conventional CT and SPECT-CT
      examination. Fifty-seven of the 71 patients had definite pathological or
      cytological diagnosis, consisting of 52 malignant lung tumors and 5 benign
      pulmonary nodules. Forty-three patients underwent surgical resection with
      different modes. Thirty-seven of the 43 surgically treated patients had available
      complete data of CT, SPECT-CT and pathological results. RESULTS: Taking the
      pathological diagnosis as gold standard, the sensitivity, specificity and
      accuracy of diagnosing pulmonary lesions suspected as lung cancer were 84.6%
      (44/52), 80.0% (4/5), 84.2% (48/57) for conventional CT and 92.3% (48/52), 80.0%
      (4/5), 91.2% (52/57) for SPECT-CT, respectively. If taking the pathological TNM
      staging results as gold standard, the concordance rates of TNM staging with
      pathological TNM staging results was 59.5% (22/37) for CT and 67.6% (25/37) for
      SPECT-CT. The sensitivity, specificity, accuracy, positive predictive value and
      negative predictive value of staging hilar and mediastinal lymph nodes were
      76.9%, 79.2%, 78.4%, 66.6%, 86.4% for conventional CT versus 61.5%, 75.0%, 70.3%,
      57.1%, 78.3% for SPECT-CT (P > 0.05), respectively. There was no statistically
      significant difference between conventional CT and SPECT-CT in the accuracy of
      diagnosing and staging for the suspected pulmonary lesions (P > 0.05).
      CONCLUSION: SPECT-CT is likely superior to conventional CT in the diagnosing and
      staging for lung cancer. It can be used as a non-invasive supplementary tool for
      differential diagnosis between malignant and benign pulmonary lesions and in
      diagnosis of lymph node > 1 cm in diameter.

PMID- 19173998
TI  - [Nedaplatin combined with tegafur in the treatment for advanced esophageal
      cancer].
AB  - OBJECTIVE: To investigate the efficacy and toxicity of nedaplatin combined with
      tegafur in the treatment for patients with advanced esophageal cancer. METHODS:
      Among the 65 patients with advanced esophageal cancer, 27 had no history of prior
      chemotherapy and the other 38 had ever received postoperative adjuvant
      chemotherapy before. The median age of those cases was 58.0 years. Nedaplatin was
      given daily by intravenous infusion at a dose of 20 mg/m(2) for 2 hours and
      tegafur at a dose of 500 mg/m(2) for 8 hours on D1 approximately D5, every 21
      days as a cycle. RESULTS: 193 cycles of chemotherapy were accomplished in the 65
      patients, and 63 patients were evaluable for response evaluation. Of 27 patients
      with no prior history of chemotherapy, 6 achieved complete response and 16
      partial response, with a response rate (CR + PR) of 81.5%. Among the 36 patients
      who had ever received postoperative adjuvant chemotherapy, 6 obtained complete
      response and 10 partial response with a response rate (CR + PR) of 44.4%. The
      overall median time to tumor progression in this series was 5.6 months. The
      overall median actuarial survival was 9.3 months, and the one-year survival rate
      was 24.9%. Nausea and vomiting were the major toxicities, but were mild and well
      tolerable. Grade 3 to 4 neutropenia was only observed in two patients (3.2%).
      CONCLUSION: The regimen of nedaplatin combined with tegafur is effective and
      tolerable for the treatment of advanced esophageal cancer.

PMID- 19174000
TI  - [Docetaxel and capecitabine combination chemotherapy for patients with
      anthracycline-resistant metastatic breast cancer].
AB  - OBJECTIVE: To evaluate the efficacy and safety of docetaxel and capecitabine
      combination chemotherapy (DC regimen) for patients with anthracycline-resistant
      metastatic breast cancer. METHODS: Thirty-two patients with anthracycline
      resistant metastatic breast cancer were treated with a docetaxel and capecitabine
      combination regimen. All patients received oral administration of capecitabine at
      a dose of 1250 mg/m(2) twice daily, within 30 min after meal on D1 to D14, and
      intravenous infusion of docetaxel at a dose of 75 mg/m(2) on D1. The regimen was
      repeated every 3 weeks. RESULTS: A total of 126 cycles of DC regimen were
      administered in the 32 cases, with a median of 4 cycles. The overall response
      rate was 46.9%. Among the 32 patients, there were complete response in 1, partial
      response in 14, stable disease in 11 and progressive disease in 6 cases. The
      median time to progression (TTP) was 5.6 months. The one-year survival rate was
      56.3%. The effective cases in different metastatic organs were: 8 cases in the
      lung, 6 cases in the liver, 3 cases in the soft tissue and 3 cases in the lymph
      nodes. The common adverse reactions were myelosuppression, hand-foot syndrome,
      nausea and vomiting. Neutropenia was observed in 84.4% of the patients. Two
      patients developed degree IV myelosuppression. CONCLUSION: The combination
      chemotherapy regimen of docetaxel plus capecitabine is well-tolerated and
      effective for anthracycline-resistant metastatic breast cancer.

PMID- 19173999
TI  - [Capecitabine combined with cisplatin as first-line therapy in Chinese patients
      with advanced gastric carcinoma-a phase II clinical study].
AB  - OBJECTIVE: To evaluate the effectiveness and safety of the combination
      chemotherapy of capecitabine (X) with fractionated administration of cisplatin
      (C) in Chinese patients with advanced gastric cancer (AGC). METHODS: 141 patients
      with AGC were enrolled between July 2002 and August 2004. All patients had
      measurable tumor according to the criteria of RECIST, Karnofsky performance
      status > or = 60, adequate bone marrow, renal and hepatic functions. Prior
      radiotherapy or adjuvant chemotherapy was not permitted. Patients received oral
      administration of capecitabine at a dose of 1000 mg/m(2) twice a day on D1-D14,
      and intravenous infusion of fractionated cisplatin at a dose of 20 mg/m(2)/day on
      D1-D5. The regimen was repeated every 3 weeks, totally for 6 cycles. RESULTS: Of
      the 141 evaluable patients, there were 104 men and 37 women, with a median age of
      54 years (range, 23 - 80 years). Metastases before chemotherapy were detected in
      lymph nodes (46.8%), liver (40.4%), lung (5.7%) and other area (10.6%). The
      median treatment duration was 6 cycles (range, 3 - 6 cycles). The objective
      response rate (RR) was 36.2% (51/141). The median follow-up period was 17.5
      months. The median time to progress (TTP) was 9.0 months, and the median overall
      survival (OS) was 12.0 months. The most common treatment-related adverse events
      (grade 3/4) were: hand-foot syndrome (HFS) (2.1%), leucopenia (0.7%), abnormal
      alanine transaminase elevation (2.8%). There was no treatment-related death.
      CONCLUSION: Capecitabine combined with fractionated cisplatin is highly effective
      and well tolerated as a first-line treatment for advanced gastric cancer, with
      comparable results to 5-Fu plus cisplatin combination therapy.

PMID- 19174001
TI  - [Understanding and controversy of the gastroesophageal junction adenocarcinoma].

PMID- 19174003
TI  - [Effect of Jagged-1 on the cytokine expression of murine myeloid-derived
      dendritic cells].
AB  - AIM: To investigate the in vitro effect of soluble Jagged-1/Fc on the cytokine
      expression of murine myeloid-derived dendritic cells induced by both rmGM-CSF and
      rmIL-4. METHODS: The DC culture model under rmGM-CSF plus rmIL-4 conditions was
      established. The influences of Jagged-1/Fc on the morphology of DC was checked,
      and the cytokine expression were analyzed by Luminex system and ELISA. The
      activation capacity of Jagged-1/Fc-induced DC for allogeneic lymphocytes was
      detected by MTT assay. RESULTS: Compared with LPS or Zymosan A, the amount of IL
      4 expression of Jagged-1/Fc-induced DC increased significantly and the amount of
      TNF-alpha expression decreased markedly but gamma-secretase inhibitor DAPT
      reversed the inhibition of Jagged-1/Fc on TNF-alpha expression from DC and
      returned it to the control level. Jagged-1/Fc altered the amount of IL-10, IL-6,
      IL-2, IL-12 and IFN-gamma expression unconspicuously and had no effect on TGF
      beta expression. The mixed lymphocyte reaction(MLR) revealed that Jagged-1/Fc
      induced DC had the weakest ability to activate allogeneic lymphocytes and LPS
      induced DC showed the strongest activation ability. CONCLUSION: The results
      indicate that Jagged-1/Fc-induced DC incline to induce immune tolerance and to
      prime naive T cells to the Th2 cells.

PMID- 19174004
TI  - [Inductive effect of RNAi RelB dendritic cells on the CD4(+)CD25(+) T cells
      proliferation].
AB  - AIM: To discover the inductive proliferation effect of the RNAi RelB dendritic
      cells (DCs) on the heterogenic CD4(+)CD25(+) T cells in mice. METHODS: The
      proportion of CD4(+)CD25(+) T cells were quantification through flow cytometer
      when each group of DCs interact with heterogenic T cells in mixed lymphocyte
      reaction, including control DCs, LPS stimulated DCs, RNAi RelB DCs and LPS
      stimulated RNAi RelB DCs. RESULTS: Control DCs stimulate more CD4(+)CD25(+) T
      cells to proliferate than LPS stimulated DCs(P<0.01). RNAi RelB DCs and LPS
      stimulated RNAi RelB DCs significantly improved CD4(+)CD25(+) T cells
      proliferation compared with LPS stimulated DCs(P<0.01). RNAi RelB DCs can also
      induced CD4(+)CD25(+) T cells to proliferate more than Control DCs (P<0.05).
      CONCLUSION: RNAi RelB DCs possess powerful potential to induce CD4(+)CD25(+) T
      cells proliferation, one of characteristics of immature dendritic cells. This
      type of RNAi RelB DCs can be used as tolerogenic DCs to regulate autoimmunity and
      other immune responses.

PMID- 19174006
TI  - [Effects of GnRH-I analog on inositol 1, 4, 5-triphosphate (IP(3)) in gastric
      parietal cells of rats in vitro].
AB  - AIM: To study the effects of Gonadotropin-releasing hormone-I (GnRH-I) analog
      alarenin on inositol 1, 4, 5-triphosphate (IP(3)) in gastric parietal cells of
      rats in vitro. METHODS: The gastric parietal cells of rats were isolated and
      incubated in vitro and alarenlin at various concentration were added to the
      medium. IP(3) was detected by radioimmunoassay. RESULTS: When alarenlin were at
      the concentration of 0.001, 0.01, 0.1, 1 micromol/L respectively, IP(3) was
      increased gradually and acted in dose-dependent way. When alarenlin was at 1
      mumol/L, IP(3) reached peak-value. Meanwhile, when 1 micromol/L alarelin were
      incubated at different time, IP(3) acted in time-dependent way. When it was
      incubated for 5 min, IP(3); reached the peak value. After the cells were
      preincubated with phospholipase c (PLC) inhibitor (compound 48/80) for 10 min,
      then added 1 micromol/L alarenlin, we found that IP(3) increased slightly, and
      there was no difference compared with the group PLC inhibitor, which only added
      PLC inhibitor (P>0.05). At the same time, after the cells were preincubated with
      IP(3) inhibitor (heparin), then added 1 micromol/L alarenlin, IP(3) also
      increased mildly, and there was no difference compared with the group IP(3)
      inhibitor, which only added IP(3) inhibitor (P>0.05). CONCLUSION: Our data
      suggest that GnRH-I analog (alarenlin) could increase the content of IP(3) in
      gastric parietal cells of rats in vitro, and IP(3) may be an important signal
      molecule in the regulation of physiological function of gastric parietal cells of
      rats.

PMID- 19174005
TI  - [Cloning and expression of human Runx3 gene obtained from human peripheral blood
      CD8(+) T lymphocyte].
AB  - AIM: Runx3, a type of Runt family member, plays an important role in immune
      regulation. In this study, we cloned and analyzed the cDNA encoding human Runx3
      from T lymphocyte, expressed Runx3 protein in E.coli system, and studied the
      relation between Runx3 and some immune disorders or tumors. METHODS: The CD8(+) T
      were isolated from human peripheral blood with MACS, Runx3 cDNA was amplified by
      RT-PCR and cloned into pMD19-T vector, and recombinant was transformed into
      competent cells DH5alpha and recombinant sequencing were performed. The identical
      was subcloned into pQE30 vector and expressed in E.coli M15. The fusion protein
      was identified by Western blot. RESULTS: The 1,248 bp fragment amplified by RT
      PCR was the same as the anticipated one in size and encodes 415 amino acids.
      Runx3 protein was gained. CONCLUSION: Human Runx3 gene was cloned and expressed
      in E.coli system successfully, which brought a foundation for further research on
      its biological function.

PMID- 19174008
TI  - [Effect of autophagy in MTB's infection and the expression of its related gene].
AB  - AIM: To study the effect of autophagy in MTB's infection and the expression of
      its related gene. METHODS: The formation of autophagy was induced by Rapamycin
      and observed by the transmission electron microscope. The cleaning role of
      autophagy to the MTB H37Rv virulent strain after its formation was detected by
      clone forming unit (CFU). Realtime PCR was used to detect the mRNA of the
      autophagy related gene was expressed. RESULTS: The RAW264.7 cell could form
      autophagosome under the induction of the Rapamycin, and it had the determinate
      cleaning role to the H37Rv strain in the cell after which formed. The mRNA of
      atg5, atg8 and atg12 which participated the formation of autophagy were expressed
      more, but the expression of atg7 had no change. CONCLUSION: Autophagy
      participated the process of immune response of anti-MTB. Atg5, atg8 and atg12
      were the important molecule which control the formation of autophagy when MTB
      infected.

PMID- 19174007
TI  - [Effect of a C-type CpG ODN on CVB3-infected mice].
AB  - AIM: To investigate the potential effect of a self-designed C-type CpG ODN (D
      SL01) on coxsackie virus B3 (CVB3) infection. METHODS: HeLa cells infected by
      CVB3 were used as cell a model and BALB/c mice inoculated with CVB3 were used as
      an animal model for evaluating the anti-viral effect of D-SL01. RESULTS: The
      supernatants of D-SL01-treated PBMC protected HeLa cells from CVB3 infection and
      Vero E6 cells from VSV infection. However, in vivo study showed that D-SL01
      reduced the body weight of CVB3-infected mice and aggravated the pathological
      changes related to myocarditis in mice when they were intraperitonealy injected
      for 6 days in succession. CONCLUSION: When used for the treatment of viral
      infected diseases in vivo, CpG ODN may function in a complicated way, which
      indicates its administration time, route and dosage, should be taken into full
      consideration.

PMID- 19174009
TI  - [Different cytotoxicity of NK cells against high and low expression of ATP
      binding cassette transporter (ABCG(2)) of human multi-drug resistant
      nasopharyngeal carcinoma cells].
AB  - AIM: To investigate the different cytotoxicity sensitivity of high and low
      expression of ATP-binding cassette transporter (ABCG(2)) of human multi-drug
      resistant nasopharyngeal carcinoma CNE2/DDP cell line (ABCG(2)(High) cell and
      ABCG(2)(Low cell)) to NK cells. METHODS: ABCG(2)(High)CNE2/DDP cells,
      ABCG(2)(Low) CNE2/DDP cells and NK cells were isolated by magnetic activated cell
      sorting (MACS). The cytotoxic effects of NK cells against K562, ABCG(2)(High) and
      ABCG(2)(Low)CNE2/DDP cells were detected with LDH releasing assay. The apoptosis
      rate and expression of NKG2D-ligands on target cells were evaluated by FCM.
      RESULTS: The expression of ABCG(2) in ABCG(2)(High) CNE2/DDP and ABCG(2)(Low)
      CNE2/DDP cells was (91.40+/-2.32)% and (1.70+/-0.24)%, respectively. More than
      90% of the isolated NK cells were CD3(-)CD16(+)CD56(+) cells. As for the
      cytotoxicity of NK cells against ABCG(2)(Low), ABCG(2)(High)CNE2/DDP and K562
      cells at the E vs T ratio of 10 vs 1 and 20 vs 1, ABCG(2)(High) CNE2/DDP cells
      possessed highest cytotoxic sensitivity. The apoptosis rate of ABCG(2)(High)
      CNE2/DDP cells and ABCG(2)(Low)CNE2/DDP cells was (12.90+/-1.51)% and (6.13+/
      0.85)%, respectively. The expression of five kinds of NKG2D ligand of
      ABCG(2);(High)CNE2/DDP cells is higher than that of ABCG(2)(Low)CNE2/DDP cells.
      CONCLUSION: ABCG(2)(High) CNE2/DDP cells are more sensitive to NK cells than
      ABCG(2)(Low) CNE2/DDP cells in cytotoxicity because the expression of NKG2D
      ligands of ABCG(2)(High)CNE2/DDP cells is higher than that of
      ABCG(2)(Low)CNE2/DDP cells, which results in the cytotoxic sensitivity of
      increased tumor cells to NK cells.

PMID- 19174010
TI  - [Expression of interleukin-17 in hepatitis B related liver fibrosis].
AB  - AIM: To explore the role of interleukin-17 (IL-17) in the pathogenesis and
      progress of chronic hepatitis B virus (HBV) related liver diseases, especially in
      hepatitis B related liver fibrosis. METHODS: Whole vein blood was obtained from
      the patients with chronic hepatitis B (CHB) (n=36), liver cirrhosis (LC) (n=42)
      including child-pugh A (n=15), child-pugh B (n=12), child-pugh C (n=15), primary
      hepatitis carcinoma (PHC) (n=34), chronic severe hepatitis (n=30) and normal
      control (n=20).The level of serum IL-17 and the expression of IL-17 mRNA in
      peripheral blood mononuclear cell (PBMC) were analysed by ELISA and RT-PCR
      respectively. Serum IL-17 and liver fibrosis index (C-IV, LN, HA) concentration
      of LC classified by child-pugh scores were detected by ELISA. RESULTS: The level
      of serum IL-17 and the expression of IL-17 mRNA in PBMC in four HBV infectious
      groups were higher than that in control group ( P<0.01). The level of serum IL-17
      and the expression of IL-17 mRNA in PBMC in LC group was higher than that in
      other groups ( P<0.01). The level of serum IL-17 and liver fibrosis index in
      child-pugh C group in LC patients were higher than that in Child-pugh B group and
      that in child-pugh B group were higher than that in child-pugh A group (P<0.01).
      The level of serum IL-17 in LC group positively correlated to child-pugh score
      and liver fibrosis index (C-IV, LN, HA) (r=0.582, 0.568, 0.682, 0.764, P<0.01).
      CONCLUSION: IL-17 is obviously increased in HBV related liver diseases,
      especially in hepatitis B related liver cirrhosis, indicating that IL-17 may play
      a part in the development of HBV related liver diseases, especially the
      pathophysiology of hepatitis B related liver fibrosis.

PMID- 19174011
TI  - [Analysis of CDR3 sequence of TCR Valpha6, Valpha10 and Vbeta23 oligoclonal T
      cells in one APL case].
AB  - AIM: To investigate the clonality and the pattern of CDR3 sequence of TCR Valpha
      and Vbeta repertoire in patients with acute promyelocytic leukemia (APL).
      METHODS: The CDR3 of TCR Valpha 29 and Vbeta 24 subfamily genes were amplified in
      mononuclear cells from peripheral blood of one case with APL using RT-PCR. The
      positive PCR products were further labeled with fluorescent and analyzed by
      genescan technique for the CDR3 size, to evaluate clonality of the detectable TCR
      Valpha and Vbeta T cells. The products of the oligoclonal T cells were analyzed
      by sequencing to define the sequence of CDR3. RESULTS: Oligoclonal T cells
      expressed TCR Valpha6, Valpha10 or Vbeta23 genes were identified from the APL
      patient. The molecular characteristics of the CDR3 of Valpha and Vbeta genes
      rearrangement were Valpha6NJalpha17, Valpha10NJalpha35 and
      Vbeta23NDbeta1NJbeta2.7. The amino acid sequence of CDR3 region in TCR Valpha 6,
      Valpha10 and Vbeta23 subfamilies were CAMRENSAGNK, YLCAGDELLWECA or
      CASSSKWAGGTYEQY, respectively. These sequences were accepted by GenBank
      (Accession Number EU544946, EU544947 and EU647219). CONCLUSION: Three idiotype
      Valpha and Vbeta sequences are identified in a case with APL, which is thought
      that may mediate the host specific immunity response for leukemia cells in APL.
      It might provide data for farther research on the specific immunotherapy of APL.

PMID- 19174012
TI  - [Preparation of human antibodies to TNF-alpha using ribosome display technology].
AB  - AIM: To prepare distinct human McAbs to TNF-alpha with high neutralizing potency
      using ribosome display technology. METHODS: The immunoglobulin heavy and light
      chain variable (VH, VL) genes were prepared from the peripheral blood lymphocytes
      in three arthritis patients by PCR. The genes encoding VH/K fragments were
      prepared by randomly combining VH and VL genes by SOE PCR. TNF-alpha binding
      fragments were selected over three cycles of ribosome display and the selected
      VH/Ks genes were cloned into pET22b(+)/BL21(DE3), from which soluble VH/K
      fragments were prepared. The expressed products of selected clones were analyzed
      by ELISA. Then the positive clones were characterized. RESULTS: A human VH/K gene
      library with 6.7x10(12) numbers used for ribosome display was constructed. Among
      the 180 selected clones, two clones TRB21 and TRB409 exhibiting the highest ELISA
      signals were isolated. The analysis of the sequence of TRB21 and TRB409 showed
      that they were new human immunoglobulin V genes to TNF-alpha and they recognize
      TNF-alpha specifically and antagonize the cytolytic effect of TNF-alpha on 1929
      cell. CONCLUSION: The selected VH/Ks to TNF-alpha will be useful for constructing
      engineering antibodies with high affinity against arthritis. Ribosome display is
      a rapid means of generating fully human antibody fragments in vitro.

PMID- 19174013
TI  - [Generation, screening and preliminary identification of specific Fab phage
      antibody library against Daudi cell strain].
AB  - AIM: To generate and screen the specific Fab phage antibody library against human
      Daudi cell strain in B-lymphoma and identify the positive clones. METHODS: BALB/c
      mice were immunized with Daudi cells, and antisera were titrated by ELISA.
      Following the demonstration of sufficient antibody titer, total RNA was extracted
      from splenic lymphocytes of the immunized mice and RT-PCR was used to amplify
      kappa light chain and Fd fragments of heavy chain. After restrictive digestion
      with Sac I/Xba I and Xho I/Spe I, the kappa light chain and the Fd fragments were
      successively inserted into the phagemid vector pComb3H-SS and then electroporated
      into E.coli XL1-Blue. The specific Fab phage antibody library against Daudi cell
      strain in human B-lymphoma was constructed by infection of helper phage VCSM13.
      Following six rounds of biopanning with Daudi cells, the antigen binding
      activities of random clones were tested by ELISA to select the positive clones,
      which were further DNA sequenced, expressed in E.coli XL1-Blue and identified by
      Western blot. RESULTS: The Fab phage antibody library with 3.13x10(7) size was
      constructed and four positive clones which specifically recognized Daudi cell
      strain were isolated. In amino acid sequences, the variable heavy domains (V(H))
      were found to be 80%-02.394% and variable light domains (V(L)) 88%-95% homologous
      with respective murine germline genes in GenBank. Furthermore, soluble Fab
      antibodies of the positive clones were successfully expressed in E.coli XL1-Blue
      and the reactivity with the membrane proteins of Daudi cells was demonstrated by
      Western blot. CONCLUSION: Fab phage antibody library is successfully constructed
      and specific antibodies against membrane antigens in Daudi cells are obtained,
      which provides an experimental foundation for the further investigation of B
      lymphoma immunotherapy.

PMID- 19174014
TI  - [Preparation, characterization and application of polyclonal antibody against
      human carboxylesterases-II].
AB  - AIM: To construct a prokaryotic plasmid expressing human carboxyles-terases-II
      (hCE-II ), purify the recombinant protein and investigate the rabbit polyclonal
      antibody against hCE-II . METHODS: A recombinant plasmid expressing pGEX-4T-1-hCE
      II (hCE-II -GST) and pET-32a- hCE-II (hCE-II -His) was constructed and then it
      was expressed in E.coli BL21 induced by IPTG. The polyclonal antibody was
      prepared by immunizing the rabbits with the purified recombinant protein. The
      sensitivity and specificity of the antibody was detected using enzyme -linked
      immunosorbent assay, immunohistochem ical staining and Western blot analysis.
      RESULTS: The polyclonal antibody against hCE-II was successfully prepared.
      Western blot analysis showed that the antibody specifically reacted with the
      recombinant protein and natural human liver microsomal proteins.
      Immunohistochemis result demonstrated that the pAb could combine with liver
      cytoplasm protein but not vascular smooth muscle cell protein. CONCLUSION: The
      successful preparation of the pAb against hCE-II with high titer and specificity
      lays a foundation for the investigation of diagnosis kit of liver cancer.

PMID- 19174015
TI  - [Focus on vocal cord paresis].

PMID- 19174016
TI  - [Vocal fold palsy--etiology and outcome].
AB  - INTRODUCTION: The etiology of vocal fold palsy (VFP) is varied, and both Danish
      and foreign studies report variable frequencies of causes. We have evaluated
      etiologies of both unilateral (UVFP) and bilateral palsy (BVFP) and also analyzed
      the outcome of the palsies. As far as we know, our material is the largest
      published in Danish. MATERIAL AND METHODS: From 01.01.2000 to 30.06.2004 229
      patients with VFP were evaluated in the ENT department of Odense University
      Hospital. We reviewed medical records and registered and analyzed data regarding
      etiology and outcome. RESULTS: Trauma caused 39% of all cases and was thereby the
      most common etiology of VFP. 27% of the cases were idiopathic. Cancer caused 22%
      of all cases, most frequent for left-sided UVFP, but also a substantial number of
      right-sided and bilateral cases were due to malignancy. Neurological disease
      caused 18% of BVFP but only 1% of UVFP. The outcome of the palsy depended on the
      etiology. VFP caused by malignancy only rarely recovered. Chances of recovery
      were greatest for idiopathic VFP or palsy caused by neurological disease, but
      also a large proportion of traumatic VFP recovered. CONCLUSION: In a large
      patient population from Funen we found that trauma was the most common cause of
      VFP. Malignancy also frequently caused VFP. The outcome depended on the etiology.
      This is important when informing patients.

PMID- 19174017
TI  - [Vocal fold palsy--investigation and follow-up].
AB  - INTRODUCTION: A new protocol for investigation of vocal fold palsy (VFP) was
      introduced in the ENT-department, Odense University Hospital on 1 January 2002.
      The protocol included ultrasonography (US) of the neck, x-ray of the chest and
      clinical examination at 3-month intervals for 1 year as well as MRI scanning of
      the brainstem, neck and mediastinum initially and after 6 months (or CT scanning
      under special circumstances). We have evaluated our protocol for investigation
      and in particular with regard to efficiency of diagnostic methods and the effect
      of long-term follow-up. MATERIAL AND METHODS: From 1 January 2002 to 30 June 2002
      we investigated 48 patients with VFP of occult origin in our department. We
      reviewed medical records and registered and analyzed data regarding efficiency of
      diagnostic methods and the effect of follow-up. RESULTS: Ten out of 48 VFP (21%)
      proved to be caused by malignancy. Eight VFP had other causes and 30 were
      idiopathic. Nine out of ten malignant diseases were found during initial
      investigation. One patient was diagnosed with breast cancer and widespread
      metastases 10 months after initial investigation. CONCLUSION: An extensive
      protocol for investigation of VFP is indicated. In our opinion, a protocol should
      include US, CT or MRI scanning of brainstem, neck and mediastinum. Our material
      is too limited to draw any final conclusions concerning long-term follow-up.

PMID- 19174018
TI  - [Assessment of thyroplasty for vocal fold paralysis].
AB  - INTRODUCTION: Thyroplasty with silicone rubber implantation is a surgical
      procedure for treatment of patients with vocal fold paralysis. The aim of the
      present study was to evaluate the outcome of the operation and to monitor which
      of the analyses were the more beneficial. MATERIAL AND METHODS: Twenty
      consecutive patients were enrolled in the study. To assess the treatment,
      videostroboscopic evaluation was performed and maximal phonation time was
      measured. A phonetogram was recorded to evaluate voice capacity and intensity,
      and a voice quality analysis was performed using the Multi-Dimensional Voice
      Program. Furthermore, patients answered the Voice Handicap Index (VHI)
      questionnaire. RESULTS: The capacity and intensity of the voice were
      significantly increased with an improvement of the highest intensity of 13 dB.
      The capacity of the voice was increased more than 2.5 times. The voice quality
      was improved significantly as measured by the jitter percentage, shimmer
      percentage and voice turbulence index. The VHI was decreased by 40, from a mean
      preoperative value of 82. A total of 90% of patients were satisfied. CONCLUSION:
      Besides videostroboscopy, a phonetogram is the most important analysis because it
      offers a quantitative measure of the voice capacity and intensity, which are the
      major problems experienced by patients with vocal fold paralysis. Used together,
      these tools are highly instrumental in guiding the patient's choice of surgery or
      no surgery.

PMID- 19174019
TI  - [Surgery for unilateral recurrent nerve paralysis].
AB  - INTRODUCTION: Medialisation surgery for unilateral recurrent nerve paralysis has
      been performed for the past 100 years to improve voice quality. The aim of this
      paper is to describe our surgical methods and evaluate the results using
      subjective and objective parameters with an emphasis on acoustic voice analysis.
      MATERIAL AND METHODS: Retrospective cohort study of 42 consecutively operated
      patients from 1996 to 2006. Twenty-eight patients were treated with a
      hydroxyapatite prosthesis, which was inserted into the larynx (VoCom), nine
      patients had a silicone bead oil injected into the paretic vocal fold, and the
      remaining five received a combination of the mentioned procedures. The subjective
      evaluation was based on the patient's description of voice quality, while
      objective quality of the voice was assessed by acoustic voice analysis performed
      with the Multi-Dimensional Voice Program (MDVP) and visual evaluation was
      performed with videostroboscopy. RESULTS: The voice quality for both surgical
      methods was improved according to subjective as well as objective parameters.
      Forty-one out the 42 patients were satisfied with their voice. The MDVP analysis
      shows an improvement of the mean values for jitter (3.74 to 1.45), shimmer (9.9
      to 4.62) and soft phonation index (23.22 to 15.61). MDVP and videostroboscopy
      show that the improvement is more easily achieved in patients with large deficits
      in glottic closure. CONCLUSION: Surgical treatment of permanent unilateral
      recurrent nerve paralysis is an effective and safe procedure which should be
      offered to all relevant patients with voice problems.

PMID- 19174021
TI  - [Congenital bilateral vocal cord paralysis].
AB  - Congenital bilateral vocal cord paralysis (CBVCP) is a rare but potentially life
      threatening condition and awareness of the condition is necessary to ensure early
      diagnosis and treatment. This case describes a 25-month-old boy suffering from
      CBVCP. The main symptoms at birth were inspiratory stridor combined with a normal
      voice and feeding problems. The difficulties in achieving the right diagnosis are
      demonstrated, and the treatment so far, including tracheotomy and a feeding tube,
      is outlined. The importance of fibre optic laryngoscopy in both diagnosis and
      control is stressed.

PMID- 19174020
TI  - [Necrosis of the tongue triggered by ergotamine in unrecognized temporal
      arteritis].
AB  - Tongue necrosis is a rare complication in arteritis temporalis. Our case is a 74
      year-old patient who presented with weight loss, tiredness and fever during a 2-3
      month period after ingestion of 2 mg ergotamine to treat her migraine. Tongue
      necrosis then occurred after ingestion of another 2 mg of ergotamine. Our patient
      had no preexisting diagnosis of arteritis temporalis. We reviewed possible
      clinical manifestations of temporal arteritis and cases of tongue necrosis in the
      world literature. It is possible that ergotamine can cause necrosis due to
      vasoconstriction of blood vessels which have an unstable blood flow.

PMID- 19174022
TI  - [Laparoscopic splenectomy--a case control study].
AB  - INTRODUCTION: Laparoscopic splenectomy (LS) is internationally considered the
      standard procedure in surgical treatment of diseases of the spleen. We present
      our initial results with LS compared with open splenectomy (OS). MATERIAL AND
      METHODS: This study is a prospective investigation of 12 elective, consecutive LS
      compared with 12 matching OS controls. RESULTS: The operation time for LS was
      significantly longer than for OS (p < 0.01). The intra-operative blood loss was
      significant lower for LS (p < 0.001) and more accessory spleens were found by LS
      (p = 0.4). Furthermore, there was a tendency towards fewer postoperative
      complications in LS (p = 0.35). The admission period was significantly reduced
      after LS (median two versus four days; p < 0.01). CONCLUSION: Based on this
      investigation and the international literature on the subject, LS seems to be a
      safe and favourable procedure for elective splenectomy, except in case of
      distinct splenomegaly. Therefore, this method should also in Denmark be
      considered the standard operation for diseases of the spleen, which will probably
      require a certain centralisation of operations.

PMID- 19174023
TI  - [Quality indicators of type 2-diabetes monitoring during 2000-2005].
AB  - INTRODUCTION: Considerable attention has been given to the screening and
      optimization of treatment of people with type 2-diabetes in the period 2000-2005.
      The aim of this paper is to evaluate the prevalence of people with type 2
      diabetes and the quality of diabetes care provided in the period 2000 to 2005.
      MATERIAL AND METHODS: Using a previously evaluated method, all patients with type
      2-diabetes were identified and described on the basis of register data in what
      was then the County of Aarhus. RESULTS: A total of 11,436 people with type 2
      diabetes were identified in the age group 40-70 years, corresponding to a
      prevalence of 4.61%. In 2005 58% were in antidiabetic pharmacological treatment,
      68% of whom received oral antidiabetic treatment, 15% were on insulin alone and
      16% received a combination treatment including insulin and oral treatment.
      Furthermore, a total of 50% of the included patients were on lipid-lowering
      treatment of whom 99% were in statin-therapy. One or more measurements of HbA1c
      were taken in 87% of the patients in 2001 compared with 81% in 2005 (p < 0.000).
      A total of 60% had an HbA1c < 8 in 2001 compared with 67% in 2005 (p < 0.000). In
      2001 72% had a cholesterol measurement compared with 77% in 2005 (p < 0.000). A
      total of 23% had a cholesterol value < 4.5. mmol/l in 2001 compared with 42% in
      2005 (p < 0.000). CONCLUSION: During a period of five years the prevalence of
      people with type 2-diabetes increased. In the same period, improvement was seen
      in the quality indicators of HbA1c and cholesterol level. There is, however,
      still room for improvement.

PMID- 19174024
TI  - [Life-saving prehospital interventions].
AB  - INTRODUCTION: The Mobile Emergency Care Unit (MECU) in Copenhagen provides
      prehospital healthcare for the citizens in the Capital Region in case of acute
      illness or accidents. The aim of this study was to describe the patients whose
      treatment was categorized by the MECU as lifesaving and to compare these with all
      other patients. MATERIAL AND METHODS: We analysed the MECU database contents and
      ambulance records from 2005 with emphasis on treatment and diagnosis. Data
      related to admission to hospital and 30-day survival were retrieved via the
      Central Population Registry. RESULTS: A total of 296 treatments were classified
      as lifesaving in 2005, corresponding to 4.3% of all patient contacts in 2005. The
      most frequent diagnoses were "opioid-poisoning" and cardiac arrest. The treatment
      given in those cases was lifesaving in 34% and 16%, respectively. This is
      significantly higher than in the cases of convulsions/unconsciousness and trauma
      where only 0.6% and 6% of the treatments were lifesaving, respectively. After 30
      days, 60.4% of the patients who received lifesaving treatment were alive. We
      found considerable differences among the individual diagnoses regarding both the
      30-day survival and the hospitalization frequency. CONCLUSION: Approximately 4%
      of patient contacts in 2005 were classified as lifesaving, they were most
      frequently related to opioid-poisoning and cardiac arrest. A total of 60% of the
      patients were alive 30 days after the intervention.

PMID- 19174025
TI  - [Laparoscopic intraperitoneal entry techniques].

PMID- 19174026
TI  - [Adult screening for attention deficit hyperactivity disorder].
AB  - ADHD is a well established condition in childhood, but much less attention has
      been given to this diagnosis among adults. It is estimated that 2-4% of the adult
      population has this condition. Adults with ADHD present symptoms that differ
      somewhat from those presenting in childhood and they are typically characterized
      by problems with planning of work and daily life activities as well as social
      persistence. The Adult ADHD Self-report Scale (ASRS) can be used in general
      practice as an introduction to the diagnostic process of ADHD in a psychiatry
      setting and to evaluate the effect of treatment. ASRS is now available in Danish
      and is recommended as a screener for adult ADHD.

PMID- 19174027
TI  - [Picture of the month: arm edema].

PMID- 19174028
TI  - [Necroticing fasciitis in children].
AB  - Necrotizing fasciitis (NF) is a serious condition with infection of the muscular
      fascia causing rapidly spreading necrosis. NF rarely affects children, and we
      here report two paediatric cases of NF. The first developed NF after a joint
      puncture, the other after surgical extirpation of a lymph node. Both were treated
      with antibiotics, human immunoglobulin, hyperbaric oxygen and repeated surgery
      and survived. In contrast to adults, children with NF often have no underlying
      chronic illness. The most frequent access point is varicella zoster ulcers.

PMID- 19174029
TI  - [Intrathoracic goiter with differential diagnostic difficulties].
AB  - Intrathoracic goiter represents an important differential diagnosis in the
      examination of lung tumours. A 71-year-old healthy woman presented with dyspnoea,
      stridor and an inhomogeneous tumour compressing the upper part of the right lung
      at the level of the left atrium. Computed tomography showed bilateral pleural
      effusions and a pericardial effusion. Thyroid scintigraphy demonstrated no uptake
      in the pulmonary mass and material from two sets of core-needle biopsies were
      inconclusive. Surgery with histology revealed a degenerated benign intrathoracic
      goiter.

PMID- 19174030
TI  - [A hybrid approach to surgery for thoracic aortic aneurysm].
AB  - A 57-year-old male, previously treated surgically with insertion of grafts for
      type A and B aortic dissection, presented with a pulsatile mass in the jugular
      fossa. Further examination verified a pseudoaneurysm the inlet of which was
      located at the proximal anastomotic site of the descending aortic graft and a
      newly developed aneurysm of the aortic arch. Using a left lateral thoracotomy to
      avoid manipulation of the pseudoaneurysm, we adopted a hybrid approach by first
      debranching the subclavian and carotid arteries from the descending aorta
      followed by endoluminal grafting of the aortic arch. The pseudoaneurysm was
      successfully excluded.

PMID- 19174031
TI  - [Where is the HIV hiding--in the patient and in the population?].

PMID- 19174032
TI  - [Cancer as acute disease shows new ways for quality development and continuing
      education].

PMID- 19174033
TI  - [General practitioners' experience from systematic review of patient cases as a
      learning vehicle in general practice].
AB  - The study shows that GPs perceive systematic reviews of patient cases as
      potential learning vehicles. This is in line with adult learning theories, which
      argue that professional capability is best enhanced by situating learning in real
      life contexts. This paper argues that we should think pragmatically when
      developing learning methods, and strengthen future efforts to develop methods
      that ensure reliable learning based on reviews of patient cases.

PMID- 19174034
TI  - [Abatacept in the treatment of active rheumatoid arthritis].
AB  - Abatacept (CTLA4Ig) is a human fusion protein which consists of a cytotoxic
      lymphocytic-associated type 4 antigen which is bound to the Fc part of the IgG1.
      Abatacept binds to CD80/CD86 on antigen-presenting cells thus blocking the co
      stimulatory signal to the naive T cells and interfering with a central
      inflammatory rheumatoid arthritis signal pathway.

PMID- 19174035
TI  - [Surgical treatment for ovarian cancer in Denmark 2004-2007].
AB  - INTRODUCTION: Previous national surveys have demonstrated that surgical treatment
      for ovarian cancer in Denmark is performed in too many low-volume departments.
      MATERIAL AND METHODS: Nationwide data from the National Patient Registry from
      January 1 December 2004-31 December 2007 including all primary operations for
      ovarian cancer and recording the number of departments, length of hospital stay
      and mortality. RESULTS: A total of 1,908 women were operated, initially at 47
      departments (stage III-IV 31 departments), a number which was reduced to eight
      departments by 2007 and further reduction to a total of six departments is
      planned in 2008. The 30-day mortality was constant (about 3.9%) over the 4-year
      period. CONCLUSION: The organisation of surgical treatment for ovarian cancer has
      improved since the Danish Health Board in 2001 recommended that operations be
      performed at five high-volume departments.

PMID- 19174036
TI  - [Valproate treatment during pregnancy: description of four cases with foetal
      valproate syndrome].
AB  - INTRODUCTION: Treatment with valproate is associated with an increased risk of
      teratogenicity compared to other antiepileptic drugs and can cause a complex of
      serious symptoms usually referred to as "foetal valproate symdrome" which is
      characterised by major and minor malformations in association with developmental
      delay. This paper aims to give attention to the syndrome through four case
      descriptions. Furthermore, possible risk factors and the use of the mutation 677C
      T as a risk marker are discussed. MATERIAL AND METHODS: Nine developmentally
      retarded children from a parent group, born of mothers who were treated with
      valproate during pregnancy, were neuropediatrically and neuropsychologically
      examined in a non-acute setting. The mothers were screened for the 677C-T
      mutation. RESULTS: Four of seven examined children fulfilled the criteria for
      foetal valproate syndrome. Only one of the four mothers was heterozygote for the
      677C-T mutation (CT, n = 1/4) and none of the mothers were homozygote (TT, n =
      0/4) CONCLUSION: The foetal valproate syndrome is a complex of symptoms which is
      probably underdiagnosed and should be considered in the diagnostic evaluation
      program for children with developmental delay who are born of mothers with
      epilepsy. The 677C-T mutation does not seem to be a useful genetic marker of this
      syndrome.

PMID- 19174037
TI  - [Minimal residual disease in malignant diseases of the blood I. Background and
      pre-clinical validation].
AB  - In haematological malignancies, molecular markers like fusion DNA from balanced
      translocations, point mutations, or over-expressed genes can now be used not only
      for diagnosis, but also for determination of the minimal residual disease (MRD)
      after cytoreduction with a sensitivity by far exceeding that of previous
      methodologies. The sensitivity of quantitative polymerase chain reaction
      typically reaches a validated identification of 1 malignant cell in 100,000.

PMID- 19174038
TI  - [Minimal residual disease in malignant diseases of the blood II. Translation and
      therapeutic consequences].
AB  - The translation of quantitative polymerase chain reaction technology for the
      quantitative detection of minimal residual disease (MRD) arising from molecular
      aberrations in leukaemias has progressed from the pre-clinical setting to daily
      clinical practice. Thus, it is now part of the mainstay in following patients
      with chronic myeloid leukaemia treated with the tyrosine kinase inhibitor
      imatinib. Moreover, the methodology is being integrated in an increasing number
      of clinical trials, where it is expected to result in more rational and
      individualized clinical decision-making. A special point in favour of the
      techniques is the powerful and early detection of disease relapses, in some cases
      up to one year prior to clinical detection.

PMID- 19174039
TI  - [Bleeding peptic ulcer. Prevalence of Helicobacter pylori and use of nonsteroidal
      anti-inflammatory drugs/acetylsalicylic acid].
AB  - INTRODUCTION: Helicobacter pylori (HP) infection and use of nonsteroidal anti
      inflammatory drugs (NSAIDs)/acetyl salicylic acid (ASA) are risk factors for
      bleeding peptic ulcer. HP eradication reduces the risk of rebleeding.
      Antibiotics, proton pump inhibitors (PPI) and presence of blood in the stomach
      can affect the HP test. The objectives of this study were to determine the HP
      prevalence and NSAID/ASA use in patients with bleeding ulcer in a low-prevalence
      HP area, to determine the proportion of idiopathic ulcers and to estimate the
      proportion of initially false negative HP tests. In addition, the objective was
      to describe changes in the characteristics of the patients who were admitted with
      ulcer bleeding during the last two decades. MATERIAL AND METHODS: Retrospective
      review of the records of patients who were admitted with a bleeding ulcer in 2003
      to 2006 at The Department of Medical Gastroenterology S, Odense University
      Hospital. Patients with initially negative or missing HP tests were offered a
      urea breath test. This population was compared with prospective registrations for
      the periods 1990-1992 and 2000. RESULTS: A total of 264 patients were admitted in
      2003-2006. The mean age was 72 years. The HP-prevalence was 34%, and 81% had used
      NSAID/ASA, as compared with 55% in 1990-1992. The proportion of idiopathic peptic
      ulcer disease was 6.6%. At admission, 19% and 17% of the patients were in
      treatment with PPI and antibiotics, respectively. Thirteen percent of the
      initially HP-negative patients were later found to be HP-positive. CONCLUSION:
      Compared to previous studies, we found a lower HP prevalence (34%) and a higher
      proportion of NSAID/ASA usage (81%) in 2003-2006. As we found 13% false negative
      HP-tests when factors that may affect the HP test were present, we advise that a
      retest be made where these factors are present and the initial HP test is
      negative.

PMID- 19174040
TI  - [Enquiries to the Danish Poison Information Centre concerning children aged 0-14
      years during a year].
AB  - INTRODUCTION: Acute drug poisoning in children poses a serious health problem.
      The present study assesses all enquiries to the Danish Poison Information Centre
      (Giftlinjen) concerning children during a one-year period. MATERIAL AND METHODS:
      All enquiries concerning children aged 0-14 years in the period 1.9.2006 to
      31.8.2007 were reviewed and the following data registered: date and nature (drug
      or other toxicant) of the poisoning, gender, age, address of the poisoned
      patient, place of poisoning, drug name, dose and the final risk assessment.
      RESULTS: Among the 9,920 enquiries to Giftlinjen, 4,399 concerned children. Among
      those, 1,060 were related to drugs. The most frequent cause of enquiry was
      related to intake of multivitamins, although these cases were mostly classified
      as not dangerous. One third (337/1,060) of all cases were categorised as
      requiring treatment, and 31/1,060 were categorised as life-threatening - often
      due to iron intake. The main part of all poisonings took place during play in the
      patient's own home (age group 0-6 years). However, there was a trend among
      patients aged 13-15 years that the poisoning was due to affective acts or a
      suicidal reaction (often with paracetamol = acetaminophen). DISCUSSION: Most drug
      poisonings in children are not dangerous. However, there is often an uncertainty
      as to the toxic dose ingested, and an individual and thorough assessment of each
      case is therefore necessary. The risk assessment and advice given by Giftlinjen
      is an important tool to avoid unnecessary contact with hospital emergency rooms
      or other health care services.

PMID- 19174041
TI  - [The role of cysteinyl leukotrienes in chronic inflammation and neoplasia of the
      intestine].
AB  - It has recently been demonstrated that cysteinyl leukotrienes are involved in a
      variety of proinflammatory and neoplastic functions. This article gives an up-to
      date overview of the present knowledge of these bioactive lipid molecules.
      Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are applied as
      models of their cellular actions. It is described how signalling cascades
      initiated by cysteinyl leukotrienes represent alternative ways in which IBD might
      progress and lead to the development and propagation of CRC, and as such
      represent potential targets for future therapeutic regimens to manage chronic
      inflammatory disorders and cancer.

PMID- 19174042
TI  - [Legionella pneumonia in patients treated with infliximab].
AB  - Therapy with tumour necrosis factor-alfa inhibitors is widely used in various
      inflammatory disorders, but adverse events from severe infections with
      intracellular pathogens may occur. We describe two cases of severe pulmonary
      legionellosis in patients treated with infliximab for Crohn's disease and
      psoriasis, respectively. We conclude that legionella infections are probably more
      frequent in patients receiving immunosuppressive therapy with tumour necrosis
      factor-alfa inhibitors than in the background population.

PMID- 19174043
TI  - [Two cases of invasive Haemophilus influenzae type f infection].
AB  - Two cases of invasive Haemophilus influenzae type f infection are presented: a
      three-week-old boy with meningitis and a 62-year-old woman with arthritis and
      bacteremia. Since 1993 vaccination against H. influenzae type b (Hib) has been
      offered to Danish children. The result has been a remarkable decrease in invasive
      Hib disease. However, physicians need to be aware of the existence of non-type b
      invasive H. influenzae disease.

PMID- 19174044
TI  - [LEOPARD syndrome].
AB  - We describe a 12-year-old boy with a typical phenotype of the LEOPARD syndrome
      (LS). The diagnosis was confirmed in the boy and his mother, who both had a
      mutation in the PTPN11 gene at Thr468Met (c.1403C > T). Several other members of
      the maternal family are suspected also to have the LEOPARD syndrome. We discuss
      the clinical characteristics of LS, the need for follow-up and genetic
      counselling, and the molecular-genetic background as well as the relationship to
      the allelic disease Noonan syndrome.

PMID- 19174045
TI  - [Introduction: update on cardiology].

PMID- 19174046
TI  - [Update on cardiovascular prevention and cardiac rehabilitation].
AB  - This article contains a review of the main developments in cardiovascular disease
      prevention reported during the last year and a discussion of recent consensus
      statements. As in previous years, a substantial part of the research effort has
      concentrated on cardiovascular risk scores, imaging techniques (particularly
      cardiac computed tomography), cardiometabolic risk factors, and exercise
      training.

PMID- 19174047
TI  - [Advances in hypertension and diabetes].
AB  - In the course of the last year, a number of important clinical trials on
      cardiovascular disease, principally in hypertensive and diabetic patients, have
      published their results. The findings, some of which were unexpected, have
      enabled us, in certain instances, to confirm what already we knew about
      controlling these risk factors, but they have also led to active discussion about
      well-established topics, such as: To what extent should blood pressure and
      glycemia levels be reduced in patients with cardiovascular disease? In addition,
      up-to-date information has become available about treating hypertension with new
      drugs or new combinations of existing drugs. This article contains a review of
      all these topics and also summarizes the findings of some observational studies
      carried out by the working group on hypertension of the Spanish Society of
      Cardiology that have been reported in the last year.

PMID- 19174048
TI  - [Update on clinical cardiology: aortic diseases, hypertrophic cardiomyopathy, and
      prophylaxis of infective endocarditis].
AB  - Although clinical cardiology encompasses the full spectrum of heart disease, in
      order to avoid overlaps with other sections we have reviewed recent developments
      reported in two substantial subject areas: aortic diseases and hypertrophic
      cardiomyopathy, which are the focus of working groups in the Clinical and
      Outpatient Cardiology working group of the Spanish Society of Cardiology. In
      addition, this article contains a critical review of new guidelines for
      antibiotic prophylaxis against infective endocarditis published by American
      scientific societies.

PMID- 19174049
TI  - [Update on pediatric cardiology and congenital heart disease].
AB  - The fields of pediatric cardiology and congenital heart disease have experienced
      considerable progress in the last few years, with advances in new diagnostic and
      therapeutic techniques that can be applied at all stages of life from the fetus
      to the adult. This article reviews scientific publications in a number of areas
      that appeared between August 2007 and September 2008. In developed countries,
      congenital heart disease is becoming increasingly prevalent in nonpediatric
      patients, including pregnant women. Actions aimed at preventing coronary heart
      disease must be started early in infancy and should involve the promotion of a
      healthy diet and lifestyle. Recent developments in echocardiography include the
      introduction of three-dimensional echocardiography and of new techniques such as
      two-dimensional speckle tracking imaging, which can be used for both anatomical
      and functional investigations in patients with complex heart disease, including a
      univentricular heart. Progress has also occurred in fetal cardiology, with new
      data on prognosis and prognostic factors and developments in intrauterine
      interventions, though indications for these interventions have still to be
      established. Heart transplantation has become a routine procedure, supplemented
      in some cases by circulatory support devices. In catheter interventions, new
      devices have become available for the closure of atrial or ventricular septal
      defects and patent ductus arteriosus as well as for percutaneous pulmonary valve
      implantation. Surgery is also advancing, in some cases with hybrid techniques,
      particularly for the treatment of hypoplastic left heart syndrome. The article
      ends with a review of publications on cardiomyopathy, myocarditis and the
      treatment of bacterial endocarditis.

PMID- 19174050
TI  - [Update on geriatric cardiology].
AB  - This article contains a review of the main developments in the field of geriatric
      cardiology reported during 2008. The focus is on research concerning the specific
      characteristics of elderly patients with heart failure, arrhythmias, ischemic
      heart disease, and aortic valve disease.

PMID- 19174051
TI  - [Update on arrhythmias and cardiac electrophysiology].
AB  - This article contains a review of the most important developments in clinical
      arrhythmology and interventional cardiac electrophysiology that have been
      reported during the past year. Special emphasis has been placed on clinical
      conditions that are most prevalent in the general population as well as on
      progress that has been achieved using the main therapeutic approaches, whether
      pharmacologic or interventional.

PMID- 19174052
TI  - [Update on ischemic heart disease].
AB  - This article contains a review of the main developments reported during 2008 in
      either publications or presentations on the pathophysiology, secondary
      prevention, prognosis or treatment of ST-segment elevation, or non-ST-segment
      elevation acute coronary syndrome. The latest clinical practice guidelines are
      also summarized and discussed.

PMID- 19174053
TI  - [Advances in heart failure].
AB  - This article reports on the most significant developments in the field of heart
      failure in the past year. Principal innovations in the management of chronic
      heart failure are explained, including the most important features of new
      management models for patients with chronic heart failure and the main advances
      in drug therapy and in the use of and indications for cardiac devices in these
      patients. In addition, recent progress in the treatment of advanced heart
      failure, with particular emphasis on acute heart failure, is reviewed. Novel
      approaches to the surgical management of patients with heart failure, including
      new contributions in the field of the circulatory support, are also highlighted
      in this update.

PMID- 19174054
TI  - [Update on interventional cardiology].
AB  - Percutaneous intervention, whether coronary or noncoronary, continues to be a
      highly active area of medicine. This article contains an overview of the most
      notable developments reported in recent months. Drug-eluting stents (DESs) have
      provided one of the major advances in interventional cardiology as they have very
      effectively reduced the restenosis rate. Both randomized clinical trials and
      large observational studies have confirmed their safety, and their use has been
      extended to include highly complex conditions. Although thrombosis is one
      complication that can affect both conventional stents and DESs, the rate of late
      stent thrombosis is slightly, though significantly, higher with DESs. Primary
      angioplasty is the treatment of choice for patients with acute myocardial
      infarction if carried out under appropriate conditions, within a reasonable time
      period in a specialized center by experienced personnel. Use of thrombectomy
      devices can improve procedural outcomes and it appears that DES implantation is
      safe and effective, though more data are still needed. In patients with non-ST
      elevation acute coronary syndrome, early treatment using an invasive approach
      coupled to the administration of various combinations of antiplatelet and
      antithrombotic drugs continues to be fundamental. Although left main coronary
      artery lesions are generally treated surgically, advances in percutaneous
      techniques and the use of DESs mean that an increasing number of patients are
      being treated using percutaneous coronary interventions. A number of studies have
      shown good results in other lesions and in high-risk patients with, for example,
      bifurcation lesions, chronic occlusions or diabetes. Intracoronary ultrasound is
      the predominant intracoronary diagnostic technique and it can be used to assist
      in optimizing DES implantation. In addition, measurement of the fractional flow
      reserve is helpful in evaluating the severity of moderate lesions whereas the
      high-resolution images provided by optical coherence tomography are particularly
      informative. Multislice computed tomography enables the presence of coronary
      artery disease to be ruled out and the technique is also useful as a
      complementary tool for interventional cardiologists. Research into regenerative
      techniques is promising but remains experimental at present. With regard to
      noncoronary interventions, new data have become available that support the use of
      a percutaneous approach in patients with patent foramen ovale. In addition,
      clinical experience with percutaneous aortic valve replacement, via either the
      transfemoral or transapical route, is increasing.

PMID- 19174055
TI  - [Progress in cardiac pacing].
AB  - This review article summarizes the fundamental principles of radiological
      protection for interventional cardiologists. In addition, the scientific articles
      on cardiac pacing that have had the greatest impact in the last year are also
      summarized. Two cardiac pacing techniques are described: His-bundle pacing and
      cardiac contractility modulation.

PMID- 19174056
TI  - [Update on cardiac imaging techniques: echocardiography, cardiac magnetic
      resonance, and multidetector computed tomography].
AB  - This article contains a review of the most important publications on cardiac
      imaging that have appeared during 2008. During the year, we assisted with the
      clinical implementation of three-dimensional real-time transesophageal
      echocardiography, with the use of echocardiography for selecting patients for and
      monitoring those who underwent percutaneous aortic valve replacement (the
      majority of centers performing the technique were still in the learning phase),
      and with the emergence in the clinic of techniques for studying myocardial
      deformation. Also reviewed are the most significant developments in the
      application of echocardiography to coronary heart disease and cardiac
      resynchronization therapy and in 2 other techniques whose use is constantly
      increasing: cardiac magnetic resonance and multidetector cardiac computed
      tomography. The review ends with a description of the current state of the art in
      contrast echocardiography, with particular emphasis on safety in the context of
      recommendations made by the US Food and Drug Administration at the end of 2007.

PMID- 19174057
TI  - Association between serum uric acid, metabolic syndrome and microalbuminuria in
      previously untreated essential hypertensive patients.
AB  - BACKGROUND AND OBJECTIVE: The aim of the study was to assess the association of
      serum uric acid levels with microalbuminuria -urinary albumin excretion (UAE)> or
      = 30mg/24h-. PATIENTS AND METHOD: Cross-sectional study in 429 (220 women)
      hypertensive, non diabetic, never treated patients (mean age: 47 years) with
      glomerular filtration rate > or =60ml/min/1.73m(2). RESULTS: The prevalence of
      microalbuminuria was 20.5%; 18% had hyperuricemia and 47% fulfilled the criteria
      for metabolic syndrome (MS). Baseline UAE correlated in the unvaried analysis to
      diastolic blood pressure, waist circumference, high-density lipoprotein
      cholesterol and uric acid. In multiple linear regression models, only MS
      (beta=0.113; p=0.03), and serum uric acid values (beta=0.04; p=0.05) were
      independently associated with logUAE, after adjustment for age and sex.
      Hyperuricemia (serum uric acid level > or =7.0mg/dl for men and > or =6.5mg/dl
      for women; odds ratio=2.18; 95% confidence interval, 1.21-3.92; p=0.010), and MS
      (odds ratio=2.16; 95% confidence interval, 1.32-3.53; p=0.002) were independently
      associated with a higher risk of microalbuminuria in multiple logistic regression
      analyses. The prevalence of microalbuminuria was 45.8% in patients with
      coexistent MS and hyperuricemia, as compared to 13.6% in hypertensive patients
      without it (p<0.001). In patients with concomitant MS and hyperuricemia the
      probability of being microalbuminuric was 3.7 times higher than in patients
      without those factors. CONCLUSION: Serum uric acid level is associated with
      microalbuminuria. Coexistence of MS and hyperuricemia in hypertensive patients
      increases almost 4 times the odds of being microalbuminuric.

PMID- 19174058
TI  - [Usefulness of the ankle-arm index for detection of peripheral arterial disease
      in a working population of Junta de Andalucia at Malaga].
AB  - BACKGROUND AND OBJECTIVE: Detection of asymptomatic peripheral arterial disease
      increases the risk of vascular morbibity and mortality. We aimed to estimate the
      prevalence of clinical and subclinical peripheral arterial disease using the
      ankle-arm index (AAI) as diagnostic tool in a working population. SUBJECTS AND
      METHOD: We included 450 workers, older than 50 years old, attending voluntary
      regular health check-up at Centro de Prevencion de Riesgos Laborales de la Junta
      de Andalucia in Malaga (Spain). We recorded clinical and anthopometrical data.
      Blood samples were taken after an overnight fast. Vascular risk was calculated
      using Framinghan and SCORE scales. Every participant was asked for symptoms of
      intermittent claudicatio and AAI was measured. AAI was considered normal within
      0.9-1.3 values. RESULTS: Most of our workers were at low- or moderate vascular
      risk. Only 48 (10.6%) of individuals had an abnormal AAI: 9 (2%) showed an
      AAI<0.9 and 39 (8.6%) showed an AAI>1.3. An AAI<0.9 was found in 19% of those
      with a SCORE risk > or = 5%, and in 11% of those having a Framinghan risk > or =
      20%. Intermittent claudication was present in 4 out of 9 (44%) of those having an
      AAI<0.9 and in 7 out of 402 (1.7%) with a normal AAI. CONCLUSIONS: Systematic
      screening of peripheral arterial disease using the AAI is not recommended in
      active working population over 50 years-old of age. Thus, AAI measurement is
      indicated only for those individuals suffering from intermitent claudicatio and
      those who are at moderate- or high vascular risk.

PMID- 19174060
TI  - [Uric acid, appreciated by all accepted by anyone].

PMID- 19174059
TI  - [Influenza vaccination and hospitalization in high risk patients].
AB  - BACKGROUND AND OBJECTIVE: We aimed to analyze the degree of utilization of
      influenza vaccines in patients who are 65 years and older with decompensated
      chronic diseases during the 2006-07 influenza epidemic and to compare it with the
      2000-01 epidemic. We also investigated the effectiveness of the influenza
      vaccination in the prevention of incomes for cardiopulmonary illness in this
      group. PATIENTS AND METHOD: Six hundred and forty two patients were studied;
      average (standard deviation) age was 74 (10) years, and 404 (63%) were males.
      Patients considered as cases had been admitted to hospital due to cardiopulmonary
      illness during the influenza season. Controls were patients attended at hospital
      but who had not been hospitalized during that period. RESULTS: The population
      vaccination rate was 445 (68%). In the vaccination group, 275 (57%) people were
      75 year old or more vs 77 (37%) patients in the non-vaccination group (p<0.001);
      418 (94%) of the vaccination group had been vaccinated in previous years, vs 96
      (46%) in the non-vaccination group (p<0.001). Cases were 337 (68%) vs 305 (31%)
      controls. Cases had major morbidity, previous hospitalization or pneumonia, as
      well as 2 or more risk factors -292 (85%) cases vs 225 (73%) controls (p<0.001)-.
      Factors mostly influencing the possibility of hospitalization were: influenza
      vaccination (odds ratio [OR]=0.59; 95% confidence interval [CI]: 0.41-0.86;
      p=0.006), chronic ischemic heart disease (OR=0.59; 95% CI, 0.40-0.88; p=0.009),
      high blood pressure (OR=1.60; 95% CI, 1.03-2.47), and previous hospitalization
      (OR=2.40; 95% CI, 1.64-3.49; p<0.001). CONCLUSIONS: In high risk patients, the
      influenza vaccination rate was improved slightly in the last 6 years. Vaccination
      was associated with less hospitalization for heart and pulmonary diseases. These
      benefits of vaccination support future efforts to increase the rates of
      vaccination among elder patients with chronic diseases, especially if they have
      not been vaccinated in previous campaigns.

PMID- 19174061
TI  - [Regulation of the medical profession].

PMID- 19174062
TI  - [Diagnosis of pulmonary embolism].

PMID- 19174063
TI  - [First-in-human clinical trials: comparison of EMEA and FDA guidelines].

PMID- 19174064
TI  - [Ankle-arm index and oscillometric method].

PMID- 19174065
TI  - [Dengue and pregnancy].

PMID- 19174066
TI  - [Gastric and rectal linitis plastica presented as metastasic breast ductal
      carcinoma].

PMID- 19174067
TI  - [Diagnosis: eruptive xanthomas].

PMID- 19174068
TI  - [Evolution of patient colonization with methicillin-resistant Staphylococcus
      aureus in a skilled nursing facility].
AB  - BACKGROUND AND OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA)
      asymptomatic colonization is common in long-term care facilities, but the burden
      of symptomatic infection appears to be low. It is not usually known whether a
      patient is colonized at the time of admission to the geriatric facility. Our
      purpose was to determine the prevalence, characteristics and factors associated
      with MRSA colonization on admission, and the cumulative incidence of colonization
      over the following 6 months. PATIENTS AND METHOD: Longitudinal and prospective
      study conducted over a 6-month period. All patients were screened at admission
      using nasal and ulcers swabs within the first 24h. Patients were screened also at
      the end of the study to assess carrier status. RESULTS: The prevalence of MRSA
      colonization was 7.6% at the entry (25 patients). In the multivariate analysis,
      advanced age, recent use of antibiotics, prior colonization by MRSA, and
      peripheral vascular disease were independent risk factors for colonization at
      admission. With standard precautions, the 6-month cumulative incidence of MRSA
      colonization was 4.2%. CONCLUSIONS: In our long-term care facility, MRSA
      colonization at the time of admission was frequent. Few patients were colonized
      during the study and no episodes of infection were reported. Probably, standard
      precautions, including hand washing and appropriate barrier procedures during the
      care of wounds, are the most useful control measures.

PMID- 19174069
TI  - [Arginine enhanced enteral nutrition, effect on blood inflammatory markers in
      head and neck cancer patients].
AB  - BACKGROUND AND OBJECTIVE: Although immune dysfunction in cancer patients could be
      multifactorial, the immune system may be modulated by specific nutritional
      substrates, such as arginine. The aim of our study was to evaluate the effect of
      enteral nutrition supplemented with a high dose of arginine on c-reactive protein
      (CRP), interleukin 6 (IL6) and tumoral necrosis factor (TNF alpha) in surgical
      head and neck cancer patients. SUBJECTS AND METHODS: At surgery, patients were
      randomly allocated to two groups: (a) enteral diet supplements with arginine
      (group I, n=18); (b) isocaloric, isonitrogenous enteral formula (group II, n=23).
      Perioperatively and on the postoperative day 6 the following parameters were
      evaluated: serum values of prealbumin, transferrin, lymphocytes, IL6, TNF alpha
      and CRP. RESULTS: The mean age (standard deviation) was 60.9 (10.6) years.
      Prealbumin and transferrin improved in both groups, CRP decreased in both groups,
      (group I: 105.1 (62.8)mg/dl vs 53.2 (51)mg/dl: p<0.05 and group II: 103.3
      (62)mg/dl vs 61.9 (57.4)mg/dl: p<0.05). IL6 improved in both groups (group I:
      38.35 (14.2)pg/ml vs 15.6 (9.1)pg/ml: p<0.05 and group II: 32.8 (35)pg/ml vs 6.8
      (4.9)pg/ml: p<0.05) TNF alpha and lymphocytes did not change. CONCLUSIONS: Both
      formulas improved IL6 and CRP levels. A high dose of enteral arginine in these
      patients did not add biochemical advantages as compared to a standard enteral
      formula.

PMID- 19174070
TI  - [Prenatal diagnosis of hemoglobinopathies and thalassemias].
AB  - BACKGROUND AND OBJECTIVE: Thalassemias are the most common single-gene disorders
      in the world population and the most important health problem in several
      countries. The best program of prevention of new births is prenatal diagnosis.
      Here we gather the experience from 1996 of the Spanish Group of Erythropathology
      related to the prenatal diagnosis of hemoglobinopathies in Spain. SUBJECT AND
      METHOD: 36 couples carriers of beta-thalassemia or Hb S were studied. Fetal
      material was obtained by amniocentesis and BCV. The genotype was determined by
      molecular biology technologies. RESULTS: We observed 3 spontaneous abortions
      (8.3%), 6 interruptions of pregnancy (16.7%) and a case of maternal contamination
      (2.8%). Prenatal diagnosis could be completed in 97.2% of the cases (35).
      CONCLUSIONS: In our experience, with regards to hemoglobinopathies, it is
      essential to provide a good genetic advice in order to identify the molecular
      alteration in the progenitors before the first pregnancy. This would allow a
      prenatal diagnosis during the first quarter and, in case of a positive result, to
      perform an early interruption of the pregnancy without risks.

PMID- 19174071
TI  - [Multi-drug resistant organisms in long-term care hospitals: a round trip
      problem].

PMID- 19174072
TI  - [Enteral nutrition support of head and neck cancer patients].

PMID- 19174073
TI  - [Mechanism involved in aged-related endothelial dysfunction].
AB  - Ageing is an important risk factor for many cardiovascular diseases with a common
      underlying circumstance: the progressive decline of endothelial function. This
      work summarizes the mechanisms involved in such dysfunction focusing our
      attention in the vasoactive substances released by the endothelium. The decrease
      of nitric oxide contribution, the enhancement of vasoconstrictor prostanoids and
      the modification of the action of either the endothelium-derived hyperpolarizing
      factor or the vasoconstrictor peptide endothelin are some of the manifestations
      that appear as the consequence of ageing in endothelial cells. The increase in
      oxidative stress, the higher production of reactive oxygen species and the
      proinflammatory phenotype of the vascular wall contribute to explain these facts.
      The role played by the senescence of endothelial cells and their progenitors is
      also revised.

PMID- 19174074
TI  - [Descriptive study on contraceptive requirements for clinical trials in Spain. Do
      we need a debate?].

PMID- 19174075
TI  - [Erythema nodosum].

PMID- 19174076
TI  - [Salt-wasting congenital adrenal hyperplasia associated to hyperreninemic
      hyperaldosteronism].

PMID- 19174077
TI  - [Paraneoplastic erythema gyratum repens and deep vein thrombosis].

PMID- 19174078
TI  - [Efficacy of premedication with intravenous corticosteroids and antihistaminics
      in preventing infusion reactions to infliximab].
AB  - AIM: Infliximab can provoke acute or delayed infusion reactions (IR) leading to
      treatment withdrawal. Our aim was to determine the frequency of IR in patients
      with inflammatory bowel disease receiving intravenous infliximab and premedicated
      with steroids and antihistaminics. METHODS: We prospectively studied 100
      consecutive patients (74 with Crohn's disease, 26 with ulcerative colitis)
      treated with infliximab induction therapy (3 doses: weeks 0-2-6), followed or not
      by maintenance every 8 weeks. All patients were premedicated with 100 mg i.v.
      hydrocortisone and 5 mg i.v. dexchlorpheniramine 30 min before each infusion.
      RESULTS: The mean age was 40.9+/-13 years (51% females, and 38% smokers). Ninety
      two percent of the patients were under immunomodulator therapy (azathioprine/
      mercaptopurine 85% or methotrexate 7%). A total of 560 infusions were
      administered, with a mean of 5.6 per patient (range, 1-21). Fifty-six percent of
      the patients received maintenance therapy. The mean length of follow-up was 17+/
      16 months. IR occurred in 6 patients (6%) and in 1.4% of all infusions (8/560).
      All reactions were mild or moderate. Five IR were immediate, occurring in the
      second infusion. One IR was delayed (exanthema 5 days after the second infusion).
      Infliximab therapy was discontinued in only 3 patients (in the patient with the
      delayed IR and in 2 patients with immediate IR that reappeared during the third
      infusion). CONCLUSION: In patients with inflammatory bowel disease treated with
      infliximab and under immunomodulator therapy, premedication with steroids and
      antihistaminics was associated with a low prevalence of IR. Moreover, after close
      follow-up, infliximab had to be discontinued in only 3% of the patients.

PMID- 19174079
TI  - [Usefulness of ultrathin transnasal endoscopy for the placement of nasoenteric
      feeding tubes].
AB  - BACKGROUND: Placement of nasoenteral feeding tubes can require endoscopic
      support. AIM: To analyze the usefulness of transnasal ultrathin endoscopy in the
      placement of nasoenteral feeding tubes. PATIENTS AND METHODS: We performed an
      ambispective study of all patients who underwent nasoenteral feeding (4.9 mm) in
      2007. RESULTS: Twenty-six procedures were performed. The mean age of the patients
      was 69.3+/-13 years. Nasal anesthesia was used in 23 patients (88.4%), and
      midazolam in 8 (30.8%). No anesthesia was used in 4 patients (15.3%).
      INDICATIONS: stenotic esophageal lesions (42.3%), distal placement to the
      pathological alteration (46.1%), and failure of placement through the normal
      route (11.5%). We placed 13 (50%) nasoduodenal, 7 (29.6%) nasogastric and 6
      (23.1%) nasojejunal tubes. The success rate was 100%. The most frequently used
      calibre was 12 F. There were no complications. CONCLUSIONS: The use of transnasal
      ultrathin endoscopy in the placement of nasoenteral feeding tubes in our patients
      was safe, effective and relatively easy.

PMID- 19174080
TI  - [Clinical and molecular features in a family with multiple endocrine neoplasia
      type-1 syndrome].
AB  - BACKGROUND: The clinical features of multiple endocrine neoplasia type-1 (MEN-1)
      syndrome are hyperplasia or adenoma of the parathyroid glands, pituitary adenoma
      and gastroenteropancreatic endocrine tumors. This syndrome is due to mutations in
      the MEN1 gene, located on the q13 region of chromosome 11. Prognosis depends on
      tumoral growth and metastatic potential. PATIENTS AND METHOD: We reviewed the
      medical records of the members of a family (6 men and 2 women) with MEN-1
      syndrome diagnosed between 1995 and 2007 in Hospital Donostia, San Sebastian
      (Spain). Familial study of all patients and family members (19 cases from 2
      generations) was performed in 2 phases. The first phase consisted of mutation
      screening and the second of multiplex ligation-dependent probe amplification
      (MLPA) to detect deletions. RESULTS: Screening of mutations identified no
      pathogenic variants in the proband of this family. MLPA revealed a deletion
      affecting exons 1 and 2 of the MEN1 gene. Of the 10 family members with this
      molecular alteration, 8 had at least one phenotypic feature of this syndrome
      (hyperparathyroidism in 8, prolactinomas in 2, and gastrinomas in 3) after 12
      years of follow-up. CONCLUSION: We discuss the clinical forms of MEN-1 syndrome
      in this family and the molecular alteration found. Study of MEN1 gene deletions
      should be incorporated into routine molecular screening.

PMID- 19174081
TI  - [Constitutional syndrome associated to metformin induced hepatotoxicity].
AB  - Metformin is an oral antidiabetic agent frequently used to manage type II
      diabetes. This drug produces nonspecific gastrointestinal symptoms in 5-20% of
      patients and, more rarely, has also been associated with severe adverse effects
      such as lactic acidosis. Only a few isolated cases of hepatotoxicity due to this
      drug have been documented. We report the case of an 83-year-old man with
      constitutional syndrome and hepatic biochemical alterations, which were
      attributed to metformin after ruling out an oncologic etiology and observing
      complete clinical and biochemical resolution after withdrawal of the drug.

PMID- 19174082
TI  - [A rare cause of gastric outlet obstruction: Bouveret's syndrome].
AB  - Bouveret's syndrome is a rare type of gallstone ileus in which a gallstone enters
      the intestinal tract via a cholecystoenteric fistula and is lodged in the
      duodenum or the stomach. Since the first description by Leon Bouveret in 1896,
      fewer than 200 cases have been described in the worldwide literature. Mortality
      is high, at 25%, but may be related to the advanced age of the typical patient
      and comorbidities, as well as diagnostic delay. Diagnosis may be made with
      radiological (abdominal X-ray, ultrasound, computed tomography or magnetic
      resonance imaging) and endoscopic techniques. Endoscopy is preferred as the first
      therapeutic option but is frequently unsuccessful and surgery is often required.
      We present the case of a patient admitted to hospital with a history of vomiting
      after eating and epigastric pain. The management of this rare cause of gastric
      outlet obstruction is discussed.

PMID- 19174083
TI  - [Clinical practice guideline on the management of rectal bleeding (update 2007)].

PMID- 19174084
TI  - [Clinical practice guideline on the treatment of hemorrhoids and anal fissure
      (update 2007)].

PMID- 19174085
TI  - [Basic mechanisms of hepatocellular injury. Role of inflammatory lipid
      mediators].
AB  - The presence of a lesion in the cellular parenchyma is common to a large number
      of chronic liver diseases, such as viral hepatitides, alcoholic hepatitis,
      chronic cholestasis and steatohepatitis. Although the pathogenesis may vary
      according to the etiological agent, a series of mechanisms is common to all.
      Notable among these mechanisms are Kupffer cell activation and inflammatory cell
      recruitment, free oxygen radical formation and the development of oxidative
      stress, cytokine production, mainly TNFa and TGFb, and inflammatory mediator
      release due to arachidonic acid oxidation through the COX-2 and 5-LO pathways.

PMID- 19174086
TI  - [Recommendations for patients with Crohn's disease starting treatment with
      adalimumab: a rapid guide].

PMID- 19174087
TI  - [Ulcerative colitis, tacrolimus and mucosa remission].

PMID- 19174088
TI  - [Ectopic or wandering spleen associated with leukopenia and thrombocytopenia].

PMID- 19174089
TI  - [Octreotide in bleeding caused by intestinal angiodysplasia].

PMID- 19174091
TI  - [Usefulness of endosonography in the etiologic diagnosis in patients with acute
      idiopathic pancreatitis].

PMID- 19174092
TI  - [Changes in "Gastroenterology and Hepatology"].

PMID- 19174093
TI  - [Analysis of the clinical benefits and cost-effectiveness of performing a
      systematic second-look gastroscopy in benign gastric ulcer].
AB  - INTRODUCTION: We analyzed the need to routinely perform a second gastroscopy
      after an initial diagnosis of benign gastric ulcer. METHOD: A total of 226
      consecutive cases of gastric ulcer were reviewed. Sensitivity (S), specificity
      (Sp), positive and negative predictive value (PPV and NPV) and the accuracy of
      the initial gastroscopy plus biopsy were analyzed, both overall and according to
      the initial endoscopist's experience (attending or resident physician). The
      diagnostic accuracy of the initial and second-look gastroscopies was compared.
      The number of second endoscopies required to diagnose a new case of malignant
      gastric ulcer and their cost was calculated, both overall and according to the
      endoscopist's experience. RESULTS: There were 178 benign ulcers (79%) and 48
      malignant ulcers (21%). The initial gastroscopy (S: 87.2%; Sp: 100%; PPV: 100%;
      PNV: 96.7%; accuracy: 96.7%) was performed by an attending physician in 74% of
      the patients and by a resident physician in the remaining 26%. Diagnostic
      accuracy was higher for attending physicians than for residents (98.2% vs. 94.8%;
      p=0.18). The accuracy of second-look endoscopy was 100%, with a significant
      improvement when compared with the initial procedure (p=0.035). Three new cases
      of MALT lymphoma and three new cases of gastric adenocarcinoma were diagnosed and
      could be treated with curative intent. The number of second gastroscopies
      required to diagnose a new case of malignant gastric ulcer and their economic
      cost was: 37.3 (4,675 Euros) for the whole group, 55.2 (6,845 Euros) for
      attending physicians and 19.3 (2,393 Euros) for residents. CONCLUSIONS: Initial
      gastroscopy showed high diagnostic accuracy, which was slightly lower when
      performed by resident physicians. Second-look gastroscopy significantly improved
      the results, confirming the clinical benefit of this procedure in diagnosing
      potentially curable malignant lesions. The mean cost of each new diagnosis of
      malignancy was 4,675 Euros, which was three times lower if the initial
      gastroscopy was performed by a less experienced endoscopist.

PMID- 19174094
TI  - [Cultural adaptation to Spanish and validation of the Gastrointestinal Short Form
      Questionnaire].
AB  - OBJECTIVE: To describe the process followed for the cultural and psychometric
      adaptation (validation) to Spanish of the Gastrointestinal Short Form
      Questionnaire (GSFQ), used to measure the interference of symptoms of
      gastroesophageal reflux disease GERD and to report the psychometric properties of
      this instrument. MATERIAL AND METHODS: The adaptation process was supervised by a
      five-member expert panel. After forward and backward translations in duplicate, a
      Spanish version was obtained, which was administered to two samples; a five
      patient pilot sample to check comprehension and face validity, and a 4,000
      patient sample to check structural validity (factor analysis and reliability),
      construct validity, and discriminative validity. RESULTS: The questionnaire
      showed a unique dimension that matched that of the original questionnaire.
      Reliability was high (alpha=0.83), and the correlation between even-odd items was
      good (r=0.69). The overall score correlated with generic health-related quality
      of life measures evaluated by the EQ-5D tariff (r=0.499) and VAS (r=-0.481). The
      scale discriminated between GERD severity levels (p<0.008) as measured by the
      Savary-Miller scale, except for the most severe level with respect to the levels
      immediately below. The questionnaire was able to detect differences between
      diverse concomitant diseases and antecedents. Sensitivity with respect to the
      GERD clinician criterion was 60.5% and specificity was 68.3%. Normative
      comparison scaling values are reported. CONCLUSIONS: The results show acceptable
      psychometric properties. A new instrument to assess the interference of GERD
      symptoms is thus available to health professionals. This instrument takes the
      patient's perspective into account.

PMID- 19174095
TI  - [Groove pancreatitis and its differential diagnosis with pancreatic
      adenocarcinoma].
AB  - We analyzed the clinical, radiographic and histologic characteristics, as well as
      the difficulties that arose in the differential diagnosis between groove
      pancreatitis (a benign entity consisting of a segmental form of chronic
      pancreatitis occurring as a sheet-like scar in the area of pancreatoduodenal
      groove) and adenocarcinoma of the pancreas. To this end, four cases with
      abnormalities in the groove area were retrospectively reviewed, three with groove
      pancreatitis, and one with adenocarcinoma of the pancreas. The important role of
      imaging techniques is highlighted, with emphasis on magnetic resonance imaging of
      the pancreas and magnetic resonance cholangiography, which reveal certain
      differentiating characteristics between these two entities. However,
      distinguishing between these entities is often difficult, and sometimes
      impossible. Consequently, cyto-histological study is always required.

PMID- 19174096
TI  - [Severe tubulo-interstitial nephritis secondary to 5-ASA].
AB  - We report a new case of chronic interstitial nephritis in a patient with
      ulcerative colitis diagnosed in 2002 who was originally treated with 5-ASA. Three
      years later deterioration of renal function was apparent with an increase in
      serum creatinine, which was normal before treatment. Withdrawal of 5-ASA led to
      partial improvement of renal function. In patients with a delayed diagnosis of
      kidney damage, recovery of renal function is incomplete and, in some cases, the
      patient even requires some form of renal replacement therapy. We stress the
      importance of monitoring renal function in patients diagnosed with inflammatory
      bowel disease treated with this drug.

PMID- 19174097
TI  - [Foreign body granuloma simulating malignant disease in the biliary tract].
AB  - Non-absorbable suture materials, such as silk, are able to form foreign body
      granulomas and stones and consequently their use should be avoided in surgical
      procedures in the biliary tract. We present the case of a patient who underwent
      surgery for a probable Klastkin tumor. During the intervention, a 1.5-cm tumor,
      with firm consistency, extrinsic to the biliary tract was found; the mass was
      extirpated with no compromise to the biliary tract. Macroscopic examination
      revealed suture (silk) material. The histopathological report described an
      inflammatory tumor, composed essentially of macrophages and foreign body giant
      cells, and identified a suture within the cell cytoplasm. The interest of this
      case lies in the rarity of this entity, the difficulty of preoperative diagnosis,
      and its possible confusion with other anatomic and clinical syndromes.

PMID- 19174098
TI  - [Risk of gastrointestinal bleeding with aspirin and platelet antiaggregants].
AB  - Aspirin is widely used for the prevention of thrombotic cardiovascular disease.
      The effect of platelet antiaggregation is achieved with low doses of 75-325
      mg/day. Due to COX-1 inhibition, associated gastrointestinal adverse effects can
      occur. Other drugs whose platelet antiaggregant effect is achieved through
      different mechanisms of action have been developed, such as clopidogrel and
      ticlopidine, which do not inhibit COX-1. The proportion of patients taking low
      dose aspirin alone or in combination with other antiaggregants is high and
      consequently the use of these drugs should be optimized by reducing their
      gastrointestinal adverse effects to a minimum. Knowledge of the risk factors that
      increase the risk of gastrointestinal adverse effects with platelet
      antiaggregants, such as age, concomitant use of other drugs such as
      anticoagulants or non-steroidal anti-inflammatory drugs, a history of peptic
      ulcer -whether complicated or uncomplicated-, and Helicobacter pylori infection,
      would help to allow management to be individually tailored to each patient. The
      use of proton pump inhibitors and/or H. pylori eradication should allow a
      positive balance, even in patients with gastrointestinal risk factors.

PMID- 19174099
TI  - [Role of nurses in gastrointestinal endoscopy].
AB  - Currently, gastrointestinal endoscopy aids diagnosis and allows minimally
      invasive therapeutic techniques to replace more aggressive interventions such as
      surgery. These advances have reduced mortality and hospital stay in patients with
      gastrointestinal disorders undergoing these procedures. Nursing professionals who
      work in endoscopy units, in addition to providing patients with the care required
      before, during and after the procedure, should have specific training to be able
      to carry out their duties in these units and to be able to manage the materials
      and equipment required, so that they may contribute to the success of these
      procedures. The specific knowledge and the development of the functions of these
      nurses aims to establish a close collaboration with the endoscopist to minimize
      the complications of the technique, reduce the patient's potential anxiety, and
      improve the applicability and results of gastrointestinal endoscopy.

PMID- 19174100
TI  - [Clostridium-difficile-associated diarrhea].
AB  - Clostridium difficile is the most frequent cause of nosocomial diarrhea and is a
      significant cause of morbidity among hospitalized patients. The inflammation is
      produced as a result of a non-specific response to toxins. In the last few years,
      a hypervirulent strain, NAP1/BI/027, has been reported. Symptoms usually consist
      of abdominal pain and diarrhea. The diagnosis should be suspected in any patient
      who develops diarrhea during antibiotic therapy or 6-8 weeks after treatment.
      Diagnosis should be confirmed by the detection of CD toxin in stool and by
      colonoscopy in special situations. The treatment of choice is metronidazole or
      vancomycin. In some patients who do not respond to this therapy or who have
      complications, subtotal colectomy may be required. Relapse is frequent and must
      be distinguished from reinfection. Prevention and control in healthcare settings
      requires careful attention.

PMID- 19174101
TI  - [What screening strategy should be recommended to the relatives of patients
      diagnosed with colorectal cancer?].

PMID- 19174102
TI  - [Functional gastrointestinal disorders: when and why might psychotherapy be
      useful in functional digestive disorders?].

PMID- 19174103
TI  - [When ultrasonography shows a solid mass in the pancreatric head of a patient
      with epigastric pain, jaundice and weight loss, how should suspicion of
      adenocarcinoma be confirmed and the degree of extension identified?].

PMID- 19174104
TI  - [Is intravenous iron really useful in inflammatory bowel disease? Would oral iron
      not be simpler and cheaper?].

PMID- 19174105
TI  - [Should the sedation required for endoscopy be administered exclusively by
      anesthetists or could it be administered safely and effectively by other medical
      specialists or by specialist nurses?].

PMID- 19174106
TI  - [What is currently the Helicobacter pylori eradication therapy of choice? Triple
      therapy (PPI, amoxicillin and clarithromycin) or sequential therapy (PPI and
      amoxicillin for 5 days followed by PPI, clarithromycin and metronidazole for a
      further 5 days)?].

PMID- 19174107
TI  - [Ingestion of Teucrium chamaedrys infusions: evidence of acute hepatitis after
      its reintroduction].

PMID- 19174108
TI  - [Combined endoscopic treatment of iatrogenic colonic perforation].

PMID- 19174109
TI  - [Toxic hepatitis associated with the use of medroxyprogesterone].

PMID- 19174110
TI  - [Chronic abdominal pain due to a mesenteric cystic lymphangioma].

PMID- 19174111
TI  - [Double pylorus: an unusual finding in a common disease].

PMID- 19174112
TI  - [From where we came from to where we are going: a new age].

PMID- 19174113
TI  - [Forced spirometry in healthy preschool children].
AB  - INTRODUCTION: Reference values for spirometry in healthy preschool children have
      not yet been obtained in accordance with American Thoracic Society (ATS) and the
      European Respiratory Society (ERS) guidelines. The objective was to establish
      reference values for spirometry in healthy preschoolers under the ATS/ERS 2007
      statement. MATERIAL AND METHOD: Children of at least 2 and under 7 years of age
      were tested in 9 pediatric pulmonary function laboratories. The technicians were
      trained to apply a standardized protocol to perform spirometry. RESULTS: Valid
      spirometry results were obtained in 455 (81.54%) out of 558 children: 242 boys
      (53.2%) and 213 girls (46.8%). Ages were as follows: 31 at least 2 and under 3
      years old; 96, at least 3 and under 4; 108, at least 4 and under 5; 122, at least
      5 and under 6 years, and 98, at least 6 and under 7 years. Formulas were used to
      calculate the reference values for all the spirometry variables in preschoolers.
      CONCLUSIONS: Spirometry is feasible in the majority of preschool children under
      the new guidelines. The availability of the reference values presented is an
      important step, both for the care of preschoolers and for further research on
      pulmonary function.

PMID- 19174114
TI  - [ECMO: experience in paediatrics].
AB  - INTRODUCTION: ECMO (Extracorporeal Membrane Oxygenation) provides a vital support
      to patients with supposed reversible respiratory and/or cardiac failure, in whom
      conventional support techniques have been previously unsuccessful. OBJECTIVES: To
      determinate the criteria used in our hospital to put paediatric patients on ECMO,
      compare their clinical course depending on their pathology (respiratory failure,
      congenital heart disease or sepsis) and identify the sequelae attributable to
      this technique. MATERIAL AND METHOD: A retrospective review of clinical records
      of all patients on ECMO support in our centre, excluding those presenting
      typically in neonatal period. RESULTS: ECMO was used on 16 patients from June
      2001 to January 2007, of which 50% were males. The median age was 7 months (from
      21 days to 11 years). The reason for starting ECMO was respiratory failure in 11
      cases (oxygenation index >40 and/or alveolar-arterial oxygen gradient >605),
      congenital heart disease in 2 and sepsis in 3 (due to shock unresponsive to
      adequate resuscitation). The median time to starting ECMO from PICU admission was
      3.58 days (from 12h to 9 days). Venovenous cannulation was used initially in 8
      patients, but 5 of them needed venoarterial ECMO later. The technique was used
      for a mean of 8 days (from 1 to 28 days). The main complication was the isolation
      of bacteria in different cultures (8 patients). The overall survival was 50% (6
      patients with respiratory failure and both patients submitted to cardiac
      surgery). Extracorporeal support was withdrawn in 7 children because their
      clinical situation was irreversible. Another patient died seven days after
      successful decannulation. We have not found any serious sequel among survivors
      that could be attributable to this technique. CONCLUSIONS: Survival among
      children supported with ECMO in our hospital is similar to that recorded by the
      ELSO in 2004, although the prognosis depends on the initial pathology. There are
      different criteria for starting this technique depending on the underlying
      diseases: respiratory index of poor prognosis in patients with respiratory
      failure, haemodynamic instability in those with sepsis or cardiac failure after
      cardiovascular surgery. We have not found any serious sequel among the survivors
      which could be attributable to this technique.

PMID- 19174115
TI  - [HIV-1 genetic variability in non Spaniard infected children].
AB  - INTRODUCTION: The prevalence of HIV-1 non-B subtypes (HIV-NBS) is increasing in
      Europe, because of emigration from countries where genetic variants are endemic.
      Although HIV-NBS could have a different clinical evolution and could respond
      differently to antiretrovirals (AR) than B-subtypes, these variant's response
      remain undocumented. AIMS: To identify HIV-1 genetic variants and to determine
      clinical evolution in a non-Spaniard children infected with HIV-1. PATIENTS AND
      METHOD: Children with HIV-1 infection from endemic countries were tested for HIV
      1 subtypes between 1-1-1988 and 31-12-2006. Twelve children less than 18 years
      old and born abroad were selected. RESULTS: HIV-NBS were isolated in 5 children
      (42%): CRF2_AG recombinant in 3 cases (Equatorial Guinea), Subtype C in one
      (Equatorial Guinea) and CRF13_cpx in last one (India). DISCUSSION: Because of the
      increasing frequency of patients with HIV-NBS and their unknown long-term
      evolution, all children from endemic countries should be tested for HIV subtypes.
      We believe new studies with more patients during longer times could reveal
      differences in these patient's clinical, immunological and virological evolution.

PMID- 19174116
TI  - [Prognostic factors for bronchiolitis complications in a pediatric intensive care
      unit].
AB  - OBJECTIVE: To analyse the prognostic factors for complications in children with
      bronchiolitis admitted to a pediatric intensive care unit (PICU). PATIENTS AND
      METHOD: A retrospective study was performed on children with bronchiolitis
      admitted into a PICU between 2000 and 2006. Univariate and multivariate analysis
      were performed to study the prognostic factors of complications, mechanical
      ventilation requirements, mortality and PICU stays of more than 15 days. RESULTS:
      A total of 110 patients were studied, of whom 72 (65.5%) had high risk factors:
      prematurity (39.1%), cardiac disease (38.2%) and bronchopulmonary dysplasia
      (16.3%). A total of 82.7% of patients had complications; 26% need invasive
      mechanical ventilation and the mortality was 3.6%, and 16.4% stayed in PICU for
      more than 15 days. Factors associated with mechanical ventilation were the
      clinical Wood-Downes score and heart disease. A weight less than 5 kg was
      associated with complications; heart disease and invasive mechanical ventilation
      were associated with a longer PICU stay; prematurity and mechanical ventilation
      were associated with mortality. CONCLUSIONS: Children with bronchiolitis admitted
      into the PICU had a high frequency of complications, often needed mechanical
      ventilation and had long stays in the PICU, but the mortality is low. The best
      prognostic factors on admission into the PICU were the acute respiratory
      insufficiency score, the presence of heart disease and were premature at birth.

PMID- 19174117
TI  - [Success and failure predictors of non-invasive ventilation in acute
      bronchiolitis].
AB  - INTRODUCTION: The objective was to identify predictive factors for non-invasive
      ventilation (NIV) failure and to describe its use in bronchiolitis. PATIENTS AND
      METHODS: Prospective observational study that included patients diagnosed with
      bronchiolitis with a modified Wood's Clinical Asthma Score 5, or oxygen
      saturation <92%, or venous CO(2) partial pressure (PCO(2)) 60 mm Hg, with no
      response to medical treatment, who received NIV from December 2005 to May 2008.
      We collected clinical data before NIV began and at 1, 6, 12, 24 and 48 h. Need
      for intubation was considered as NIV failure. RESULTS: NIV was successful in 83%
      of 47 cases included. Patients in whom NIV failed had lower weight (5.2+/-2.2 vs.
      3.5+/-0.8 kg, P=.011), lower age [1.8 (0.3-12.3) vs. 0.8 (0.4-4.3) months,
      P=.038)], lower heart rate (HR) before NIV began (176.3+/-19.1 vs. 160.4+/-9.7
      beats/minute, P=.010), lower HR decrease at hours 1 (-16.0+/-17.3 vs.+1.1+/-11.6,
      P=.005) and 12 (-31.5+/-19.7 vs. -0.75+/-12.2, P=.002), presence of apnoeas
      (23.1% vs. 75%; P=.004) and of a predisposing condition (84.6% vs. 50%; P=.029).
      Multivariate analysis identified the absence of a predisposing condition, and a
      greater HR decrease during the first hour as success-associated independent
      factors (OR 0.004; 95% CI 0.000-0.664 and OR 0.896; 95% CI: 0.809-0.993,
      respectively). CONCLUSIONS: NIV has a high success rate in bronchiolitis. The
      main parameters which can predict NIV success are the absence of a predisposing
      condition and a higher HR decrease in the first hour.

PMID- 19174118
TI  - [Heliox-driven bronchodilator nebulization in the treatment of infants with
      bronchiolitis].
AB  - INTRODUCTION: Heliox is a helium-oxygen mixture which improves laminar flow and
      decreases airway resistance and the work of breathing. The aim of this study was
      to assess the effects of salbutamol or epinephrine nebulization driven by heliox
      in infants with moderate-to-severe bronchiolitis. MATERIALS AND METHODS: This
      prospective, observational, interventional, controlled and randomized study
      included ninety-six children who came to our pediatric emergency department with
      first episode of moderate-to-severe bronchiolitis. The patients were randomized
      to receive salbutamol or epinephrine nebulized with either oxygen (control group)
      or heliox (70% helium and 30% oxygen) as the driving gas. Heart rate, respiratory
      rate, pulse oximetry oxygen saturation and clinical score were measured before
      and after the treatment period. We also reported hospitalization rates and the
      number of patients who returned to the emergency department in the following
      seventy two hours. RESULTS: There were no significant differences between both
      groups. The only statistically significant difference was that, in the heliox
      group, patients with severe bronchiolitis needed a lower number of nebulizations
      than infants in the control group. CONCLUSIONS: According to our study, heliox
      driven salbutamol or epinephrine is not an effective therapy in patients with
      acute bronchiolitis.

PMID- 19174119
TI  - [Special needs of schoolchildren with diabetes mellitus. Point of view of parents
      and teachers].
AB  - BACKGROUND: The daily care of a diabetic (IDDM) child is essential for the short
      and long term evolution of the disease, and must include the hours the child
      spends in school. The presence of Trained personnel are needed who will be able
      to intervene in time if a serious complication, such as hypoglycemia, occurs.
      Their presence can help to ensure correct control of the disease and avoid long
      term complications. OBJECTIVES: To understand of the day to day life of children
      with IDDM, focusing on their school hours. To understand the attitude of primary
      and secondary school teachers towards pupils with IDDM. PATIENTS AND METHODOLOGY:
      Descriptive and transversal study on IDDM patients between the ages of 3 and 18,
      treated within the Healthcare Area number 3 in the Madrid Region, and their
      teachers. Two different kinds of surveys were distributed: the 1st survey by
      Fundacion para la Diabetes (Foundation for Diabetes) contained 80 questions aimed
      at patients between the ages of 3 and 18 and their parents. Questions were
      related to patient's daily life and school environment. The 2nd survey, which
      allowed free response, was aimed at primary and secondary school teachers about
      their own experiences working as professionals with pupils with IDDM. RESULTS:
      Fifty questionnaires addressed to parents and patients were valid in our remit,
      and we emphasize the following: the ages of major participation were 10 to 14
      years; 86% of children knew how to measure blood glucose and 66% how to
      administer insulin; 74% had no problems with school integration, however, up to
      50% of children under 6 years had suffered a problem occasionally; on the 50% of
      the occasions when a patient needed insulin administration during school hours,
      it was done by a relative; 66% of hypoglycaemias were resolved by the patient.
      Health personnel is present only in 8% of the schools studied; 98% of those
      surveyed think teachers should have written instructions on the signs and
      symptoms and action to be taken if a hypoglycemia occurs. Questionnaires for
      teachers were answered by 54% of them (76 of a total of 140), we would like to
      point out the following: 71% of them recognise having a diabetic pupil; the
      degree of teacher knowledge on diabetes, rated on a scale from 1 to 7 shows a
      median of 3 and a mode of 4; 47% of teachers feel insecure when having a diabetic
      pupil because they do not have instructions on actions to take in case a
      complication occurs; 97% of teachers affirm to know what a hypoglycaemia is,
      however only 67% and 57% of them recognise its signs and symptoms and know how to
      act when they occur. CONCLUSIONS: The school integration and acceptance of pupils
      with IDDM is good, according to both teachers and parents. Children with IDDM
      take responsibility for their disease at an early age and are able to develop
      certain skills. However they still need help, which they get from their family
      even during school hours. Generally, teachers are willing to learn new skills to
      be able to help these children, however, further training is required to improve
      the understanding and management of this disease.

PMID- 19174120
TI  - [Thyroid disorders and childhood rheumatic diseases].
AB  - INTRODUCTION: The relationship between thyroid dysfunction and autoimmune
      diseases has mainly been described in adults. The aim of this study was to
      analyse the prevalence and characteristics of thyroid abnormalities in children
      with rheumatic diseases. PATIENTS AND METHOD: One hundred and forty-five patients
      (109 girls and 36 boys) from a rheumatology paediatric unit were studied for two
      years. The diagnoses were: juvenile idiopathic arthritis (JIA) (n=115), lupus
      (n=17), juvenile dermatomyositis (n=5), scleroderma (n=4), and one case each of
      the following: mixed connective mixed disease, CINCA syndrome (chronic infantile
      neurological, cutaneous and articular), TRAPS (tumour necrosis factor receptor
      associated periodic syndrome), and familial mediterranean fever. T4 and TSH
      levels were carried out, and if these showed abnormalities, antithyroid
      antibodies (ATA) were determined. RESULTS: Six girls aged between 2 and 17 years
      old had thyroid abnormalities. Three had JIA and three had lupus. Five were
      diagnosed with autoimmune hypothyroidism, with high ATA levels, and there was one
      case of hyperthyroidism. All of the patients with thyroid dysfunction had
      positive antinuclear antibodies (ANA), compared to 34.5% of the rest of the
      patients (p=0.003). CONCLUSIONS: The prevalence of thyroid abnormalities in
      children with rheumatic disease was 4.14% to 7.9% in JIA patients with positive
      ANA, and up to 17.6% with lupus. The majority of patients were asymptomatic.
      Thyroid hormones should be determined when rheumatic disease is diagnosed and
      periodically afterwards.

PMID- 19174121
TI  - [Malignant thymoma associated with severe aplastic anaemia].
AB  - Malignant thymoma is a very rare neoplasm in paediatric patients; it is usually
      associated with para-neoplastic syndromes, the most frequent is myasthenia
      gravis; some haematological abnormalities may also be present, such as pure red
      cell aplasia or aplastic anaemia. We report a 12-year-old boy suffering from a
      very large thymoma, treated with multiple chemotherapy, and who developed a
      severe aplastic anaemia after surgery. He had a poor response to
      immunosuppressive treatment and later developed massive pulmonary bleeding as a
      complication.

PMID- 19174122
TI  - [Castleman's disease: presentation of an atypical case].
AB  - Castleman's disease is an unknown etiology lymphoproliferative disorder rare in
      childhood (only 100 cases described in the literature, 7 of them in Spain). It
      usually appears in young adults, with no gender-related differences. There are
      two clinical forms of the disease: the localized variant, the more frequent type,
      usually presented as a solitary mass (generally in the mediastinum) and
      asymptomatic at the time of diagnosis, and the multicentric variant, less
      frequent and usually associated with systemic symptoms and a more aggressive
      clinical evolution. The diagnosis is confirmed based on the histopathological
      study. There are two histological variants: the hyaline-vascular type, which
      usually appears as a localised variant, and the plasma-cell type, which usually
      appears as multicentric variant and has a worse prognosis. While the best
      treatment for the localised variant is surgical resection, which is curative, for
      the multicentric variant many therapeutic strategies have been used without real
      success. In the present article we report a new case of this disease in a 3-year
      old girl with the localised form, who remains asymptomatic after two years of
      follow-up, and a review of the available literature. This disease should be
      included in the differential diagnosis of the lymphoproliferative disorders.

PMID- 19174123
TI  - [Update on new insulins].
AB  - Standard human insulin preparations such as regular soluble insulin and neutral
      protamine Hagedorn (NPH) insulin have shortcomings in terms of their
      pharmacokinetic and pharmacodynamic properties that limit their clinical
      efficacy. In the last decade, due to advances in genetic engineering,
      structurally modified insulin molecules have been developed with the aim of
      changing their galenic properties to make regular soluble insulin faster and NPH
      insulin slower. Five insulin analog preparations have become commercially
      available: two long-acting analogs (insulin glargine and detemir) and three rapid
      or fast-acting analogs (insulin lispro, aspart and glulisine). This article
      highlights the specific properties of these new insulin analog preparations and
      focuses on their potential advantages and disadvantages when used in children
      with diabetes mellitus.

PMID- 19174124
TI  - [Vaccination schedule of the Spanish association of pediatrics: recommendations
      2009].
AB  - Based on the available evidence, we, the Vaccine Advisory Committee (CAV) of the
      Spanish Association of Pediatrics (Asociacion Espanola de Pediatria, AEP),
      provide information about and comments on vaccine-related innovation during 2008.
      Modifications to the Vaccine Schedule for 2009 are also discussed. The importance
      of the recommendation of administration of a varicella booster at start of school
      (3-4 years of age) is highlighted according to the technical specifications of
      one of the vaccines. The importance of making the heptavalent pneumococcal
      conjugate vaccine universally available is reiterated in accordance with the
      unquestionable results of scientific tests, WHO recommendations, the posture
      adopted by the majority of neighboring European countries, and the decision taken
      in 2006 by the autonomous community of Madrid (Spain). New scientific reasons are
      provided, corroborating the recommendation made by this committee in 2008, for
      the implementation by Spanish pediatricians of the vaccine against rotavirus and
      human papilloma virus. With regard to the latter, vaccination should be from 11
      to 16 years of age, and then extended, in accordance with the technical
      specifications of the available vaccine preparations, to 26 years of age. As part
      of the recommendations, we insist that children in risk groups should be given
      flu vaccine and hepatitis A vaccine. The committee considers that these two
      vaccines must also be given, when pediatricians consider it appropriate, to
      children other than those in risk groups. This recommendation can be regarded as
      the first step towards a future recommendation of universal vaccination. Finally,
      this year we include an appendix with recommendations and vaccination strategies
      to be followed in children who have not previously received vaccines or who have
      not been completely immunized.

PMID- 19174125
TI  - [Subacute subdural haematoma associated with an arachnoid cyst].

PMID- 19174126
TI  - [X-linked West syndrome].

PMID- 19174127
TI  - [Familial 18p syndrome -- a clinical case].

PMID- 19174128
TI  - [Kabuki syndrome in the differential diagnosis of neonatal hypotonia].

PMID- 19174129
TI  - [Belated diagnosis of congenital hypothyroidism].

PMID- 19174130
TI  - [Co-existing coeliac and inflammatory bowel disease].

PMID- 19174131
TI  - [Immersion-induced spontaneous pneumomediastinum].

PMID- 19174132
TI  - [Malignant hyperthermia syndrome after a routine intubation in an infant].

PMID- 19174133
TI  - [Difficult differential diagnosis of bone infarction and osteomyelitis in a girl
      with drepanocytosis].

PMID- 19174134
TI  - [A presentation of two female siblings with a disease caused by a cat scratch].

PMID- 19174135
TI  - [A giant congenital melanocytic nevus with a proliferative nodule].

PMID- 19174136
TI  - Bacterial predators.

PMID- 19174137
TI  - Scaling in biology.

PMID- 19174138
TI  - Erroneous quadruped walking depictions in natural history museums.

PMID- 19174139
TI  - Evolution: how fruit flies adapt to seasonal stresses.
AB  - Fruit flies inhabit a wide range of latitudes, requiring adaptation to the
      varying local climates. A recent study reports evidence that the ability of North
      American flies to endure the winter involves adaptive polymorphism of the couch
      potato gene.

PMID- 19174140
TI  - Neuronal homeostasis: does form follow function or vice versa?
AB  - Nerve cells adjust their electrical excitability and the overall strength of
      synaptic connections to maintain their functional identity. A recent study
      suggests that they may also regulate dendritic branch patterns to compensate for
      the variability of synaptic contacts and help ensure appropriate connectivity in
      the brain.

PMID- 19174141
TI  - Cell division: experiments and modelling unite to resolve the middle.
AB  - How does a cell find its middle? New experiments confirm that activating stable
      microtubules together with inhibitory dynamic microtubules are key ingredients.
      Quantitative modelling has now further scrutinised these ideas, yielding fresh
      insights into furrow positioning.

PMID- 19174142
TI  - Mammalian vision: rods are a bargain.
AB  - To maintain resting potentials in darkness, rod and cone photoreceptors incur a
      significant energy cost. But in brighter light, rods become energetically
      'cheaper' than cones, which might explain the evolution of the vertebrate duplex
      retina.

PMID- 19174143
TI  - Leaf development: untangling the spirals.
AB  - How do plants position their leaves and flowers around the stem in such regular
      patterns? Auxin is well established as an essential regulator. Now, the
      modification of a structural cell wall component is shown to have a dramatic
      impact.

PMID- 19174144
TI  - Meiosis: DDK is not just for replication.
AB  - How is the chromosome segregation machinery modified to segregate homologs during
      meiosis I? The Dbf4-dependent Cdc7 kinase (DDK) has now been identified as a key
      regulator in this process.

PMID- 19174145
TI  - Cognitive neurology: stimulating research on neglect.
AB  - A recent brain stimulation study provides the first direct physiological evidence
      that attention deficits after right-hemisphere stroke arise in part from hyper
      excitation of neural pathways in the undamaged left hemisphere.

PMID- 19174146
TI  - Biological optics: deep reflections.
AB  - An image-forming optical system that is based on a mirror with an unconventional
      structure has recently been discovered in a deep-sea fish.

PMID- 19174147
TI  - The puzzle of plastid evolution.
AB  - A comprehensive understanding of the origin and spread of plastids remains an
      important yet elusive goal in the field of eukaryotic evolution. Combined with
      the discovery of new photosynthetic and non-photosynthetic protist lineages, the
      results of recent taxonomically broad phylogenomic studies suggest that a re
      shuffling of higher-level eukaryote systematics is in order. Consequently, new
      models of plastid evolution involving ancient secondary and tertiary
      endosymbioses are needed to explain the full spectrum of photosynthetic
      eukaryotes.

PMID- 19174148
TI  - Plasmodium falciparum signal peptide peptidase is a promising drug target against
      blood stage malaria.
AB  - The resistance of malaria parasites to current anti-malarial drugs is an issue of
      major concern globally. Recently we identified a Plasmodium falciparum cell
      membrane aspartyl protease, which binds to erythrocyte band 3, and is involved in
      merozoite invasion. Here we report the complete primary structure of P.
      falciparum signal peptide peptidase (PfSPP), and demonstrate that it is essential
      for parasite invasion and growth in human erythrocytes. Gene silencing suggests
      that PfSPP may be essential for parasite survival in human erythrocytes.
      Remarkably, mammalian signal peptide peptidase inhibitors (Z-LL)(2)-ketone and L
      685,458 effectively inhibited malaria parasite invasion as well as growth in
      human erythrocytes. In contrast, DAPT, an inhibitor of a related gamma
      secretase/presenilin-1, was ineffective. Thus, SPP inhibitors specific for PfSPP
      may function as potent anti-malarial drugs against the blood stage malaria.

PMID- 19174149
TI  - UBXD1 binds p97 through two independent binding sites.
AB  - The chaperone-related p97 protein plays a central role in various cellular
      processes involving the ubiquitin-proteasome system. The diverse functions of p97
      are controlled by a large number of cofactors that recruit specific substrates or
      influence their ubiquitylation state. Many cofactors bind through a UBX or PUB
      domain, two major p97 binding modules. However, the recently identified UBXD1
      cofactor possesses both domains. To elucidate the molecular basis underlying the
      interaction between UBXD1 and p97, we analyzed the contribution of both domains
      to p97 binding biochemically and in living cells. The PUB domain mediated robust
      binding to the carboxy-terminus of p97, while the UBX domain did not contribute
      to p97 binding. Importantly, we identified an additional p97 binding site in
      UBXD1 that competed with the p47 cofactor for binding to the N domain of p97.
      This novel, bipartite binding mode suggests that UBXD1 could be an efficient
      regulator of p97 cofactor interactions.

PMID- 19174150
TI  - 1,5-Anhydro-D-fructose attenuates lipopolysaccharide-induced cytokine release via
      suppression of NF-kappaB p65 phosphorylation.
AB  - Lipopolysaccharide (LPS) stimulates macrophages by activating NF-kappaB, which
      contributes to the release of tumor necrosis factor (TNF)-alpha and interleukin
      (IL)-6. 1,5-Anhydro-D-fructose (1,5-AF), a monosaccharide formed from starch and
      glycogen, exhibits anti-oxidant activity and enhances insulin secretion. This
      study examined the effects of 1,5-AF on LPS-induced inflammatory reactions and
      elucidated its molecular mechanisms. Before LPS challenge, mice were pretreated
      with 1,5-AF (38.5 mg/kg). We found that 1,5-AF pretreatment attenuated cytokine
      release into the serum, including TNF-alpha, IL-6 and macrophage chemoattractant
      protein (MCP)-1. Furthermore, pretreatment with 1,5-AF (500 microg/ml) attenuated
      cytokine release, and 1,5-AF directly inhibited the nuclear translocalization of
      the NF-kappaB p65 subunit in LPS-stimulated murine macrophage-like RAW264.7
      cells. This inhibition was responsible for decreased LPS-induced phosphorylation
      on Ser536 of the NF-kappaB p65 subunit, which is a posttranslational modification
      involved in the non-canonical pathway. Collectively, these findings indicate that
      the anti-inflammatory activity of 1,5-AF occurs via inactivation of NF-kappaB.

PMID- 19174151
TI  - tBHQ inhibits LPS-induced microglial activation via Nrf2-mediated suppression of
      p38 phosphorylation.
AB  - Role of microglial Nrf2 activation in preventing neuronal death caused by
      microglial hyperactivation is investigated by using BV-2 microglial cells as
      modulator and primary neurons as target. Pretreatment of microglial cells with
      tBHQ, a phenolic antioxidant activating Nrf2, attenuated the LPS-derived
      overproduction of pro-inflammatory neurotoxic mediators like TNF-alpha, IL-1beta,
      IL-6, PGE(2), and NO as well as the morphological changes associated with
      microglial hyperactivation. Pretreatment of BV-2 cells with tBHQ suppressed LPS
      induced phosphorylation of p38 required for overproduction of neurotoxic
      mediators. Results obtained using Nrf2-specific shRNA showed that expression of
      Nrf2 in microglia plays a critical role in tBHQ-derived suppression of LPS
      induced p38 phosphorylation and microglial hyperactivation. Conditioned culture
      media taken from LPS-stimulated microglia cause neuronal death. However, the
      conditioned media taken from tBHQ-pretreated and LPS-stimulated microglia did not
      cause death of primary neurons. This suggested that prior activation of Nrf2 in
      microglia may inhibit microglial hyperactivation and prevent neuronal death.

PMID- 19174152
TI  - Fyn kinase is a direct molecular target of delphinidin for the inhibition of
      cyclooxygenase-2 expression induced by tumor necrosis factor-alpha.
AB  - Tumor necrosis factor (TNF)-alpha-mediated cyclooxygenase (COX)-2 expression
      plays key roles in inflammation and tumorigenesis, particularly skin
      carcinogenesis, and hence targeting the TNF-alpha-mediated signaling pathway
      might be a promising strategy for developing chemopreventive agents against skin
      cancer and other skin disorders. Here we report that Fyn kinase - one of the
      members of the nonreceptor protein tyrosine kinase family - is involved in TNF
      alpha-induced COX-2 expression, and that delphinidin - a major anthocyanidin
      present in red wine and berries - inhibits these effects by directly inhibiting
      Fyn kinase activity. Delphinidin strongly inhibited TNF-alpha-induced COX-2
      expression in JB6 P+ mouse epidermal (JB6 P+) cells, whereas two other major
      phenolic compounds (resveratrol and gallic acid) did not exert significant
      inhibitory effects. Delphinidin inhibited the TNF-alpha-induced phosphorylations
      of JNK, p38 MAP kinase, Akt, p90RSK, MSK1, and ERK, and subsequently blocked the
      activation of the eukaryotic transcription factors AP-1 and NF-kappaB. Kinase and
      pull-down assay data revealed that delphinidin inhibited Fyn kinase activity and
      directly bound with Fyn kinase noncompetitively with ATP. By using PP2 (a
      commercial inhibitor of Fyn kinase) and siRNA-Fyn, we confirmed that Fyn kinase
      is involved in TNF-alpha-induced COX-2 expression mainly by down-regulating JNK
      in JB6 P+ cells. Together these findings suggest that the targeted inhibition of
      Fyn kinase activity and COX-2 expression by delphinidin contributes to the
      chemopreventive potential of red wine and berries.

PMID- 19174153
TI  - Linking anemia to inflammation and cancer: the crucial role of TNFalpha.
AB  - Erythropoiesis is considered as a multistep and tightly regulated process under
      the control of a series of cytokines including erythropoietin (Epo). Epo
      activates specific signaling pathways and leads to activation of key
      transcription factors such as GATA-1, in order to ensure erythroid
      differentiation. Deregulation leads to a decreased number of red blood cells, a
      hemoglobin deficiency, thus a limited oxygen-carrying capacity in the blood.
      Anemia represents a frequent complication in various diseases such as cancer or
      inflammatory diseases. It reduces both quality of life and prognosis in patients.
      Tumor necrosis factor alpha (TNFalpha) was described to be involved in the
      pathogenesis of inflammation and cancer related anemia. Blood transfusions and
      erythroid stimulating agents (ESAs) including human recombinant Epo (rhuEpo) are
      currently used as efficient treatments. Moreover, the recently described
      conflicting effects of ESAs in distinct studies require further investigations on
      the molecular mechanisms involved in TNFalpha-caused anemia. The present study
      aims to evaluate the current knowledge and the importance of the effect of the
      proinflammatory cytokine TNFalpha on erythropoiesis in inflammatory and malignant
      conditions.

PMID- 19174154
TI  - Metabolism-blocked antifolates as potential anti-rheumatoid arthritis agents: 4
      amino-4-deoxy-5,8,10-trideazapteroyl-d,l-4'-methyleneglutamic acid (CH-1504) and
      its analogs.
AB  - 4-Amino-4-deoxy-5,8,10-trideazapteroyl-d,l-4'-methyleneglutamic acid (CH-1504) is
      the prototype of a potentially therapeutically more selective class of
      antifolates for rheumatoid arthritis treatment. This class is characterized by
      retention of dihydrofolate reductase (DHFR; EC 1.5.1.3) as their locus of action
      and transport by the reduced folate carrier (RFC; SLC19A1), but their lack of
      metabolism by known pathways of antifolate (e.g., methotrexate (MTX)) metabolism.
      Five new CH-1504 analogs (CHL-001-CHL-005) were synthesized and diastereomers of
      CH-1504 itself were obtained by preparative chiral HPLC; all were characterized
      biochemically. The analogs are not metabolized by aldehyde oxidase (EC 1.2.3.1),
      carboxypeptidase G2 (EC 3.4.17.11), or (excepting CHL-003) folylpolyglutamate
      synthetase (EC 6.3.2.17) and thus, unlike MTX, are "metabolism-blocked". All
      analogs are potent DHFR inhibitors; several are nearly as potent as MTX or CH
      1504. Each analog uses the RFC for transport, although with varying apparent
      affinities. In contrast, each weakly inhibits other enzymes of folate metabolism
      relevant to rheumatoid arthritis therapy (thymidylate synthase (EC 2.1.1.45), two
      formyltransferases of purine biosynthesis (EC 2.1.2.2 and EC 2.1.2.3), and 5,10
      methylenetetrahydrofolate reductase (EC 1.5.1.20)). Biochemical characterization
      showed one 4'-diastereomer of racemic CH-1504 was significantly more active than
      the other. Based on literature data concerning the effect of d- and l-glutamic
      acid substitution on antifolate activity, it is likely that the diastereomer
      containing l-4'-methylene-glutamic acid is the more active. Because of concern
      about potential pharmacokinetic and biochemical effects of d-4'-methylene
      glutamic acid-containing species, these data suggest that future analogs should
      contain only l-4'-methylene-glutamic acid. Overall, these data provide several
      interesting new leads for preclinical development.

PMID- 19174155
TI  - Cyclophilin B stimulates RNA synthesis by the HCV RNA dependent RNA polymerase.
AB  - Cyclophilins are cellular peptidyl isomerases that have been implicated in
      regulating hepatitis C virus (HCV) replication. Cyclophilin B (CypB) is a target
      of cyclosporin A (CsA), an immunosuppressive drug recently shown to suppress HCV
      replication in cell culture. Watashi et al. recently demonstrated that CypB is
      important for efficient HCV replication, and proposed that it mediates the anti
      HCV effects of CsA through an interaction with NS5B [Watashi K, Ishii N, Hijikata
      M, Inoue D, Murata T, Miyanari Y, et al. Cyclophilin B is a functional regulator
      of hepatitis C virus RNA polymerase. Mol Cell 2005;19:111-22]. We examined the
      effects of purified CypB proteins on the enzymatic activity of NS5B. Recombinant
      CypB purified from insect cells directly stimulated NS5B-catalyzed RNA synthesis.
      CypB increased RNA synthesis by NS5B derived from genotype 1a, 1b, and 2a HCV
      strains. Stimulation appears to arise from an increase in productive RNA binding.
      NS5B residue Pro540, a previously proposed target of CypB peptidyl-prolyl
      isomerase activity, is not required for stimulation of RNA synthesis.

PMID- 19174156
TI  - KB-34, a newly synthesized chalcone derivative, inhibits lipopolysaccharide
      stimulated nitric oxide production in RAW 264.7 macrophages via heme oxygenase-1
      induction and blockade of activator protein-1.
AB  - Chalcones, a subclass of the flavonoid family, are widely known for their anti
      inflammatory and anti-oxidative properties. In the present study, we synthesized
      the chalcone derivative, KB-34 (3-Phenyl-1-(2,4,6-tris
      (methoxymethoxy)phenyl)prop-2-yn-1-one), and examined its effect on nitric oxide
      (NO) production. KB-34 potently inhibited nitrite production in RAW 264.7
      macrophages stimulated by lipopolysaccharide (LPS). KB-34 treatment also markedly
      inhibited inducible nitric oxide synthase (iNOS) expression, as assessed by
      Western blot and quantitative RT-PCR analyses. Treatment of cells with KB-34
      significantly inhibited LPS-induced transcriptional activation by activator
      protein-1 (AP-1) as determined by luciferase reporter gene assay, whereas nuclear
      factor-kappaB (NF-kappaB) activity was not affected by KB-34, indicating that
      down-regulation of iNOS gene expression by KB-34 is mainly attributed by blockade
      of AP-1 activation. We also demonstrated that KB-34 treatment led to an increase
      in heme oxygenase-1 (HO-1) mRNA and protein expression, mediated by stimulating
      the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2). Treatment
      with SnPP, a selective inhibitor of HO-1, reversed the KB-34-mediated inhibition
      of nitrite production, suggesting that HO-1 plays an important role in the
      suppression of NO production by KB-34. In contrast, SnPP treatment did not
      counteract the KB-34-mediated suppression of AP-1 activity, suggesting that
      inhibition of AP-1 activation by KB-34 is independent of HO-1 induction. Taken
      together, these results indicate that KB-34 suppresses NO production in LPS
      stimulated RAW 264.7 macrophages via simultaneous induction of HO-1 expression
      and blockade of AP-1 activation. This study reveals that KB-34 would be a
      promising agent for the treatment of inflammation-associated disease.

PMID- 19174157
TI  - Inhibition of renin/prorenin receptor attenuated mesangial cell proliferation and
      reduced associated fibrotic factor release.
AB  - The present study was designed to investigate the physiological roles of
      renin/prorenin receptor in cultured rat mesangial cells. The presence of
      renin/prorenin receptor in mesangial cells was determined by immunofluorescence
      staining, real-time quantitative reverse transcriptase-polymerase chain reaction
      (real-time PCR) and Western blotting assay. The expression of renin/prorenin
      receptors was identified in both rat renal slices and cultured mesangial cells.
      Meanwhile, the cultured mesangial cells were demonstrated synthesizing and
      secreting (Pro)renin as well. Knockdown of renin/prorenin receptor expression was
      performed by small interfering RNA (siRNA) transfection. Either knockdown or
      blockade of renin/prorenin receptor by handle region peptide (HRP) reduced
      mesangial cell proliferation. In the meantime, release of type IV collagen,
      phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and
      mRNA level of transforming growth factor-beta1 (TGF-beta1) were decreased. On the
      other hand, both the production and activity of matrix metalloproteinase-2, a key
      enzyme to degrade type IV collagen, was increased. The present results indicated
      that renin/prorenin receptor played a regulatory role in mesangial cells
      proliferation and extracellular matrix accumulation. Blockade of renin/prorenin
      receptors may postpone over extracellular accumulation, which occurs in some
      pathological situations, via suppressed both mesangial cell proliferation and
      fibrotic factor release.

PMID- 19174158
TI  - Inducible expression of Wnt genes during adult hepatic stem/progenitor cell
      response.
AB  - In injured livers where hepatocyte growth is severely limited, facultative
      hepatic stem/progenitor cells, termed oval cells in rodents, are known to emerge
      and contribute to the regeneration process. Here, we investigated a possible
      involvement of Wnt signaling during mouse oval cell response and found
      significant upregulation of several Wnt genes including Wnt7a, Wnt7b, and Wnt10a.
      Accordingly, increase of beta-catenin protein was observed in oval cell
      compartments. Pharmacological activation of the canonical Wnt/beta-catenin
      signaling induced proliferation of cultured hepatic stem/progenitor cell lines.
      These results together implicate the role of Wnt/beta-catenin signaling in adult
      hepatic stem/progenitor cell response.

PMID- 19174159
TI  - Characterization of the endonuclease SSO2001 from Sulfolobus solfataricus P2.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) and their
      associated protein genes (cas genes) have been suggested to act as an immune
      system in archaea and bacteria mimicking the eukaryotic RNA interference (RNAi)
      system. We have investigated the properties of the protein SSO2001 from
      Sulfolobus solfataricus (Sso) P2, which is part of the cas gene cluster. This
      study shows that SSO2001 is an endonuclease specifically digesting double
      stranded oligonucleotides and preferably cleaving at G:C pairs. Point mutations
      identify both highly conserved aspartate and glutamate residues as being crucial
      for the nuclease activity. The catalytic activity shows an optimum at neutral pH
      and pH 3.

PMID- 19174160
TI  - Hypotonic shocks activate rat TRPV4 in yeast in the absence of polyunsaturated
      fatty acids.
AB  - Transient-receptor-potential channels (TRPs) underlie the sensing of chemicals,
      heat, and mechanical force. We expressed the rat TRPV1 and TRPV4 subtypes in
      yeast and monitored their activities in vivo as Ca(2+) rise using transgenic
      aequorin. Heat and capsaicin activate TRPV1 but not TRPV4 in yeast. Hypotonic
      shocks activate TRPV4 but not TRPV1. Osmotic swelling is modeled to activate
      enzyme(s), producing polyunsaturated fatty acids (PUFAs) to open TRPV4 in
      mammalian cells. This model relegates mechanosensitivity to the enzyme and not
      the channel. Yeast has only a single Delta9 fatty-acid monodesaturase and cannot
      make PUFAs suggesting an alternative mechanism for TRPV4 activation. We discuss
      possible explanations of this difference.

PMID- 19174161
TI  - Interplay between poxviruses and the cellular ubiquitin/ubiquitin-like pathways.
AB  - Post-translational polypeptide tagging by conjugation with ubiquitin and
      ubiquitin-like (Ub/Ubl) molecules is a potent way to alter protein functions
      and/or sort specific protein targets to the proteasome for degradation. Many
      poxviruses interfere with the host Ub/Ubl system by encoding viral proteins that
      can usurp this pathway. Some of these include viral proteins of the membrane
      associated RING-CH (MARCH) domain, p28/Really Interesting New Gene (RING) finger,
      ankyrin-repeat/F-box and Broad-complex, Tramtrack and Bric-a-Brac (BTB)/Kelch
      subgroups of the E3 Ub ligase superfamily. Here we describe and discuss the
      various strategies used by poxviruses to target and subvert the host cell Ub/Ubl
      systems.

PMID- 19174162
TI  - A sorghum 85kDa heat stress-modulated protein shows calmodulin-binding properties
      and cross-reactivity to anti-Neurospora crassa Hsp 80 antibodies.
AB  - The present study, carried out to identify stress-modulated calmodulin (CaM)
      binding proteins in sorghum, resulted in the isolation of several proteins, which
      showed binding to CaM-Sepharose matrix. Calmodulin gel overlay assay and MALDI
      ToF MS analysis revealed that an 85kDa protein (Hsp85), which interacted with
      calmodulin, cross-reacted with anti-N. crassa Hsp80 antibodies. Since these
      antibodies bind to plant Hsp90, sorghum Hsp85 is likely to be a member of the
      Hsp90 family. This study provides the first evidence that a member of Hsp90
      (Hsp85) in plants exhibits CaM-binding properties.

PMID- 19174163
TI  - Proteomic and genomic analysis of PITX2 interacting and regulating networks.
AB  - Pituitary homeobox 2 (PITX2) is a homeodomain transcription factor that has a
      substantial role in cell proliferation and differentiation in various tissues. In
      this report, we have conducted a systematic study, using proteomic and genomic
      approaches, to characterize PITX2-interacting proteins and PITX2-regulating
      genes. We identified four novel PITX2-associated protein partners Y box binding
      factor-1, heterogeneous ribonucleoprotein K, nucleolin and heterogeneous nuclear
      ribonucleoprotein U in mass spectrometry analysis. We also found that
      overexpression of PITX2 upregulated 868 genes (2-25-fold) and downregulated 191
      genes (2-15-fold) in DNA microarray analysis. These data provide an insightful
      perspective for further studying PITX2 function and mechanism of action.

PMID- 19174164
TI  - Role of the N-terminal domain of FliI ATPase in bacterial flagellar protein
      export.
AB  - FliI, the ATPase involved in bacterial flagellar protein export, forms a complex
      with its regulator FliH in the cytoplasm and hexamerizes upon docking to the
      export gate composed of integral membrane proteins. The extreme N-terminal region
      of FliI is involved not only in its interaction with FliH but also in its
      oligomerization, but the regulatory mechanism of oligomerization remains unclear.
      Using in-frame 10-residue deletions within the 100 residues of the N-terminal
      domain, we demonstrate that the first 20 residues are required for FliH binding
      and that the conformation of the N-terminal domain is sensitive to the export
      function, even though the oligomerization and FliH-binding ability are retained
      and the ATPase activity is maintained in most of the deletion variants.

PMID- 19174165
TI  - Androgens and dominance: sex-specific patterns in a highly social fish
      (Neolamprologus pulcher).
AB  - In most vertebrates, aggression and dominance are tightly linked to circulating
      testosterone. Fish, however, have two androgens (testosterone, T and 11
      ketotestosterone, 11KT) that influence aggression and dominance. To date, few
      studies have compared the relationship between androgen levels and the outcome of
      aggressive contests in both females and males of the same species. To investigate
      sex differences in androgens we staged size-matched, limited-resource (territory)
      contests with 14 female-female and 10 male-male pairs of the highly social
      cichlid Neolamprologus pulcher. We then examined androgen levels in recently
      established dominants, who won the contest and subsequently acquired a territory
      (for 3h), and subordinates, who lost and did not acquire a territory. Newly
      dominant females had higher plasma T but similar 11KT levels to newly subordinate
      females. In contrast, newly dominant males had higher 11KT but similar T levels
      to subordinate males. The ratio of 11KT to T, which demonstrates physiological
      importance of T conversion to 11KT, was positively correlated with submissive
      behavior in female winners, and correlated weakly with aggressive behavior in
      male winners (p=0.05). These findings provide support for the hypothesis that
      different androgens play equivalent roles in female versus male dominance
      establishment, and suggest that relative levels of 11KT and T are implicated in
      female dominance behavior and perhaps behavior of both sexes.

PMID- 19174166
TI  - 'Fit-for-purpose' validation of SearchLight multiplex ELISAs of angiogenesis for
      clinical trial use.
AB  - Validated assays of circulating biomarkers of angiogenesis to predict and
      determine the efficacy of vascular-targeted anticancer drugs would facilitate
      successful drug development. Multiple biomarker candidates exist and a multiplex
      approach was sought to minimise the requisite patient blood volume and to aid
      selection of those biomarkers with greatest potential clinical utility.
      Validation of the SearchLight multiplex ELISA platform comprising two multiplex
      assays of nine potential angiogenesis biomarkers was conducted (plex 1; VEGF R1
      and R2, IL-8, KGF, PlGF; plex 2; PDGFbb, HGF, FGFb and VEGF). The study focused
      on instrument qualification, analyte specificity within the multiplex format,
      assay precision and reproducibility. No evidence was found within the multiplex
      that signals output from one analyte impinged on another or that antibody cross
      reactivity occurred. Spike recovery for 5 between-experiment repeats was within
      +/-15% of input values for 7 of the 9 multiplexed analytes, with a coefficient of
      variation (CV) of <20% for 6 of the 9 analytes. Plasma samples from 8 ovarian
      cancer patients (who were not receiving therapy) were assessed using the two
      multiplexes on this platform to explore the likely baseline variability in this
      disease context. This study suggests that the platform and the multiplex approach
      will be useful to evaluate pharmacodynamic responses to vascular targeted therapy
      in early clinical trials.

PMID- 19174168
TI  - Informed Generation: physical origin and biological evolution of genetic
      codescript interpreters.
AB  - The information stored in the genome of an organism has long been thought of in
      computational terms as a kind of codescript for the construction, operation and
      control of the system in which it is found. However, genomic sequence information
      can be interpreted as biological instructions and executed as a genetic
      codescript only by a suitably prepared cell with which the program is in proper
      registration. We enquire into the character of the evolutionary process that
      generates physical systems capable of interpreting, in increasingly elaborate
      ways, the genetic information they contain. The principle of Informed Generation
      specifies the need for the spontaneous emergence and evolutionary development of
      self-organizing processes that generate phenotypes from genotypes. The principle
      of Informed Generation describes a ubiquitous feature of biological systems:
      without the prior existence of certain components or functionalities, which are
      required for the production of themselves and others, no configuration of genetic
      information that accumulated through Natural Selection could ever serve as a
      codescript for an organism. The operation of Informed Generation is demonstrated
      in the stepwise evolution of genetic coding and the general distinction between
      Natural Selection and Informed Generation is illustrated through consideration of
      gene-replicase-translatase (GRT) system. It is proposed that Informed Generation
      represents a quite general process of evolutionary self-organization in
      biological systems whereby essentially irreversible transitions in the systems'
      dynamics take them to historically contingent, isolated states whose
      characteristics are determinants of biological specificity. The operation of
      Informed Generation may have left detectable traces in topographical features of
      complex intracellular and ecological networks.

PMID- 19174167
TI  - Inheritance of epigenetic chromatin silencing.
AB  - Maintenance of alternative chromatin states through cell divisions pose some
      fundamental constraints on the dynamics of histone modifications. In this paper,
      we study the systems biology of epigenetic inheritance by defining and analyzing
      general classes of mathematical models. We discuss how the number of modification
      states involved plays an essential role in the stability of epigenetic states. In
      addition, DNA duplication and the consequent dilution of marked histones act as a
      large perturbation for a stable state of histone modifications. The requirement
      that this large perturbation falls into the basin of attraction of the original
      state sometimes leads to additional constraints on effective models. Two such
      models, inspired by two different biological systems, are compared in their
      fulfilling the requirements of multistability and of recovery after DNA
      duplication. We conclude that in the presence of multiple histone modifications
      that characterize alternative epigenetic stable states, these requirements are
      more easily fulfilled.

PMID- 19174169
TI  - An HBV model with diffusion and time delay.
AB  - In this paper, a hepatitis B virus (HBV) model with spatial diffusion and
      saturation response of the infection rate is investigated, in which the
      intracellular incubation period is modelled by a discrete time delay. By
      analyzing the corresponding characteristic equations, the local stability of an
      infected steady state and an uninfected steady state is discussed. By comparison
      arguments, it is proved that if the basic reproductive number is less than unity,
      the uninfected steady state is globally asymptotically stable. If the basic
      reproductive number is greater than unity, by successively modifying the coupled
      lower-upper solution pairs, sufficient conditions are obtained for the global
      stability of the infected steady state. Numerical simulations are carried out to
      illustrate the main results.

PMID- 19174170
TI  - Traveling wave formation in vertebrate segmentation.
AB  - In vertebrate somitogenesis, "segmentation clock" genes (such as her in
      zebrafish, hairy in chick, and hes in mouse) show oscillation, synchronized over
      nearby cells through cell-cell interaction. The locations of high gene expression
      appear with regular intervals and move like a wave from posterior to anterior
      with the speed slowing down toward the anterior end. We analyze traveling wave
      pattern of her gene expression when there is an anterior-posterior gradient of
      one of the reaction rates in the gene-protein kinetics. We adopt a model which
      includes the kinetics of mRNA and proteins of her gene in each cell and cell-cell
      interaction by Delta-Notch system explicitly. We show that the observed spatio
      temporal pattern can be explained if mRNA degradation, protein translation,
      protein transportation to nucleus occurs faster, or mRNA transcription, Delta
      protein synthesis occurs slower in posterior than in anterior regions. All of
      these gradients are those that produce longer periodicity of oscillation of clock
      gene expression in the anterior than in the posterior. Based on this result, we
      derive a mathematical formula for how the peak of gene expression moves along the
      pre-somitic mesoderm.

PMID- 19174171
TI  - Supplementation of curcumin and vitamin E enhances oxidative stress, but restores
      hepatic histoarchitecture in hypothyroid rats.
AB  - AIMS: In the present study, the effects of vitamin E and curcumin on hepatic
      dysfunction, mitochondrial oxygen consumption as well as hyperlipidemia in
      hypothyroid rats are reported. MAIN METHODS: Adult male rats were rendered
      hypothyroid by administration of 0.05% 6-n-propyl-2-thiouracil (PTU) in their
      drinking water, while vitamin E (200 mg/kg body weight) and curcumin (30 mg/kg
      body weight) were supplemented orally for 30 days. KEY FINDINGS: Hypothyroidism
      induced elevation in serum aspartate aminotransferase activity was found to
      decline in vitamin E and curcumin treated rats. Nevertheless, distorted
      histoarchitecture revealed in hypothyroid rat liver was alleviated to normal by
      vitamin E and curcumin treatment. Regulation of hypothyroidism induced decrease
      in complexes I and II mediated mitochondrial respiration by vitamin E and
      curcumin was found to be different. Administration of curcumin to hypothyroid
      rats alleviates the decreased state 4 respiration and increased respiratory
      control ratio (RCR) level in complex I mediated mitochondrial oxygen consumption,
      whereas complex II mediated respiration was not influenced by exogenous
      antioxidants. Although, increase in serum concentration of total cholesterol was
      not modified by exogenous antioxidants, increased level of non-high-density
      lipoprotein cholesterol (non-HDL-C) in serum of hypothyroid rats was further
      enhanced by vitamin E and curcumin. Moreover, a significant elevation in
      mitochondrial lipid peroxidation and protein carbonylation was noticed in
      hypothyroid groups treated with vitamin E and curcumin. SIGNIFICANCE: The present
      study suggests that supplementation of curcumin and vitamin E enhances oxidative
      stress parameters and hyperlipidemia; nevertheless, it protects hypothyroid
      induced altered rectal temperature, serum transaminase activity and hepatic
      histoarchitecture.

PMID- 19174172
TI  - Metabolic Engineering with power-law and linear-logarithmic systems.
AB  - Metabolic Engineering aims to improve the performance of biotechnological
      processes through rational manipulation rather than random mutagenesis of the
      organisms involved. Such a strategy can only succeed when a mathematical model of
      the target process is available. Simplifying assumptions are often needed to cope
      with the complexity of such models in an efficient way, and the choice of such
      assumptions often leads to models that fall within a certain structural template
      or formalism. The most popular formalisms can be grouped in two categories: power
      law and linear-logarithmic. As optimization and analysis of a model strongly
      depends on its structure, most methods in Metabolic Engineering have been defined
      within a given formalism and never used in any other. In this work, the four most
      commonly used formalisms (two power-law and two linear-logarithmic) are placed in
      a common framework defined within Biochemical Systems Theory. This framework
      defines every model as matrix equations in terms of the same parameters, enabling
      the formulation of a common steady state analysis and providing means for
      translating models and methods from one formalism to another. Several Metabolic
      Engineering methods are analysed here and shown to be variants of a single
      equation. Particularly, two problem solving philosophies are compared: the
      application of the design equation and the solution of constrained optimization
      problems. Generalizing the design equation to all the formalisms shows it to be
      interchangeable with the direct solution of the rate law in matrix form.
      Furthermore, optimization approaches are concluded to be preferable since they
      speed the exploration of the feasible space, implement a better specification of
      the problem and exclude unrealistic results. Beyond consolidating existing
      knowledge and enabling comparison, the systematic approach adopted here can fill
      the gaps between the different methods and combine their strengths.

PMID- 19174173
TI  - Using empirical social contact data to model person to person infectious disease
      transmission: an illustration for varicella.
AB  - With the aim to improve dynamic models for infections transmitted predominantly
      through non-sexual social contacts, we compared three popular model estimation
      methods in how well they fitted seroprevalence data and produced estimates for
      the basic reproduction number R(0) and the effective vaccination level required
      for elimination of varicella. For two of these methods, interactions between age
      groups were parameterized using empirical social contact data whereas for the
      third method we used the current standard approach of imposing a simplifying
      structure on the 'Who Acquires Infection From Whom' (WAIFW) matrix. The first
      method was based on solving a set of differential equations to obtain an
      equilibrium value of the proportion of susceptibles. The second method was based
      on finding a solution for the age-specific force of infection using the formula
      of the mass action principle by means of iteration. Both solutions were
      contrasted with observed age-specific seroprevalence data. The best fit of the
      WAIFW matrix was obtained with contacts involving touching, and lasting longer
      than 15min per day. Plausible values for R(0) for varicella in Belgium ranged
      from 7.66 to 13.44. Both approaches based on empirical social contact data
      provided a better fit to seroprevalence data than the current standard approach.

PMID- 19174174
TI  - Bilateral dopaminergic lesions in the ventral tegmental area of rats influence
      sucrose intake, but not umami and amino acid intake.
AB  - The role of the dopaminergic cells in the ventral tegmental area (VTA) in
      response to natural rewards is important in understanding palatability-induced
      feeding behavior. In this study, we first investigated whether dopaminergic
      lesions in the VTA would influence the taste preferences of rats for sodium
      chloride (NaCl), monosodium glutamate (MSG), disodium inosine-5'-monophosphate
      (IMP), disodium guanine-5'-monophosphate (GMP) and sucrose. Among these taste
      stimuli, only the preference of sucrose solutions decreased significantly in the
      VTA lesioned rats, preferences for the other taste stimuli were unaffected.
      Secondly, we tested whether VTA lesioned rats made slightly deficient in the
      amino acid lysine (by feeding rats a lysine deficient diet for five days) would
      detect the deficient amino acid in a choice test. Both the VTA lesioned rats and
      the control rats chose to consume the lysine solution and there was no difference
      between these two groups. These results suggest that the dopaminergic neurons in
      the VTA influence sucrose consumption, but do not alter the consumption of
      palatable umami compounds and salt. They also do not inhibit the animal's ability
      to recognize the essential amino acid lysine when the animal is deficient in it.
      Different central pathways must underlie sucrose preference and preferences for
      these amino acids and ribonucleotides.

PMID- 19174175
TI  - Development of a cell-based assay for high-throughput screening of inhibitors
      against HCV genotypes 1a and 1b in a single well.
AB  - The Hepatitis C (HCV) replicon system is a useful tool for the high-volume
      screening of inhibitors of HCV replication. In this report, a cell-based assay
      has been described, which monitors the inhibition of HCV genotypes 1a and 1b as
      well as cytotoxicity, from a single well of a 96-well plate. A mixture of two
      stable replicon cell lines was used: one containing a 1a-H77 replicon expressing
      a firefly luciferase reporter, and the other one containing a 1b-N replicon with
      a secreted alkaline phosphatase reporter, thus allowing us to monitor replication
      of two HCV genotypes in the same well. Cytotoxicity was measured using the
      Resazurin cytotoxicity assay. The assay was validated with known HCV inhibitors
      and showed that the antiviral activity and cytotoxicity of compounds were
      reproducibly measured under screening conditions. It was also showed that the
      assay's signal-to-noise ratio and Z' coefficient were suitable for high
      throughput screening. A panel of HCV inhibitors showed a good correlation between
      EC(50) and TD(50) values for 1a and 1b replicon activity and cytotoxicity
      measured using either a single replicon format or mixed replicon format. Thus,
      the use of this mixed replicon format provides an economical method for
      simultaneous measurement of compound activity against two HCV genotypes as well
      as cytotoxicity, thereby reducing cost of reagents and labor as well as improving
      throughput.

PMID- 19174176
TI  - The immunogenicity of CpG-antigen conjugates.
AB  - Compared to "live" vaccines the immunogenicity of "split" vaccines is notably
      poor, because exogeneous antigens (Ag) insufficiently access the MHC class I
      processing pathway needed for cross-presentation. Here we review our evidence
      that targeting ligands of endosomally expressed Toll-like Receptors (TLRs),
      together with exogeneous Ag to endosomes of dendritic cells (DCs) conveys
      immunogenicity to Ag similar in magnitude as "live" vaccines that produce Ag. We
      explored the consequences of enforced endocytosis of "Ag plus TLR ligands" either
      by crosslinking Ag and CpG-Oligonucleotides (CpG-Ag conjugates) or by co
      encapsulating Ag plus endosomally expressed TLR ligands in biodegradable
      microspheres (MP). While both approaches equally well yielded in effective cross
      priming of MHC class I restricted CD8 T effector cells, our data recommend MP as
      a generally applicable endosomal delivery device to vaccinate for protective and
      therapeutic CD4 and CD8 T cell immunity. Furthermore, our data suggest that
      functional inactivation of Foxp3(+) regulatory T cells further enhances the
      immunogenicity of "split vaccines".

PMID- 19174177
TI  - Refining HPV 16 L1 purification from E. coli: reducing endotoxin contaminations
      and their impact on immunogenicity.
AB  - HPV 16 L1 capsomeres purified from Escherichia coli represent a promising and
      potentially cost-effective alternative to the recently licensed VLP-based
      vaccines for the prevention of cervical cancer. However, recombinant protein
      preparations from bacteria always bear the risk of contaminating endotoxins which
      are highly toxic in humans and therefore have to be eliminated from vaccine
      preparations. In this study, we measured the LPS concentration at various stages
      of the purification of HPV 16 L1 from E. coli and determined that it enhances the
      immunogenicity of HPV 16 VLPs and capsomeres. We confirmed the immunogenicity of
      the L1 capsomeres in TLR4(-/-) mice without the enhancing effect of the LPS and
      then elaborated a suitable protocol using Triton X-114 phase separation for the
      removal of LPS without any significant protein loss or influence on the
      structural integrity of the particles. The LPS-free capsomeres purified from E.
      coli induced neutralizing L1-specific antibodies. Our results demonstrate the
      excellent potential of capsomeres as an economically interesting alternative
      vaccine to prevent cervical cancer that could be made available in developing
      countries.

PMID- 19174178
TI  - Effects of infectious bronchitis virus vaccine on the oviduct of hens.
AB  - In Australia, currently, all pullets reared for egg production are vaccinated
      with live attenuated strains of infectious bronchitis virus. Various vaccines and
      protocols to control this viral disease have been developed, although the
      severity of the disease varies from place to place and flock to flock. In the
      present trial, the effects of vaccine strains A3 and Vic S on the oviduct of
      laying hens were assessed by histopathology, electron microscopy, serology and
      also by determining the presence and persistence of viral RNA in the oviduct by
      real time PCR following the experimental infection. Birds were either
      unvaccinated or vaccinated with both A3 and Vic S and then mock-infected,
      challenged with the same attenuated strains, either A3 or Vic S. Some respiratory
      signs were observed, but were mild and short-lived. There was no drop in egg
      production in any of the groups. However, there was visual loss of shell colour
      in the unvaccinated hens challenged with the Vic S strain. Mild histopathology
      was recorded only in terms of lymphocyte infiltration and occasional submucosal
      oedema in the infundibulum and very mild gland dilatation in the magnum.
      Microscopic lesions were not recorded in the isthmus, tubular shell gland or
      shell gland pouch. Cilia loss was not observed in any region of the oviduct using
      scanning electron microscopy. Both the A3 and Vic S vaccine strains were detected
      in the oviduct of vaccinated and unvaccinated hens, mainly on the 12th day p.i.
      These results indicate that the A3 and Vic S strains replicate at a low level in
      the oviduct without causing significant damage and hence are safe for the
      oviduct.

PMID- 19174179
TI  - The control parameters used by the CNS to guide the hand depend on the visuo
      motor task: evidence from visually guided pointing.
AB  - To perform visually guided hand movements the visuo-motor system transforms
      visual information into movement parameters, invoking both central and peripheral
      processes. Central visuo-motor processes are active in the CNS, whereas
      peripheral processes are active at the neuromuscular junction. A major share of
      research attention regarding central visuo-motor processes concerns the question
      which parameters the CNS controls to guide the hand from one point to another.
      Findings in the literature are inconsistent. Whereas some researchers suggest
      that the CNS controls the hand displacement vector, others suggest that it
      controls final hand position. The current paper introduces a paradigm and
      analysis method designed to identify the parameters that the CNS controls to
      guide the hand. We use simulations to validate our analysis in the presence of
      peripheral visuo-motor noise and to estimate the level of peripheral noise in our
      data. Using our new tools, we show that hand movements are controlled either in
      terms of the hand displacement vector or in terms of final hand position,
      depending on the way visual information relevant for movement production is
      specified. Interestingly, our new analysis method reveals a difference in central
      visuo-motor processes, even though a traditional analysis of movement endpoint
      distributions does not. We estimate the level of peripheral noise in our data to
      be less than or equal to 40%. Based on our results we conclude that the CNS is
      flexible with regard to the parameters it controls to guide the hand; that
      spatial distributions of movement endpoints are not necessarily indicative of
      central visuo-motor processes; and that both peripheral and central noise has to
      be carefully considered in the interpretation of movement data.

PMID- 19174180
TI  - Evidence that increased 5-HT release evokes region-specific effects on blood
      oxygenation level-dependent functional magnetic resonance imaging responses in
      the rat brain.
AB  - This study aimed to determine the potential of in vivo functional magnetic
      resonance imaging (fMRI) methods as a non-invasive means of detecting effects of
      increased 5-HT release in brain. Changes in blood-oxygenation level-dependent
      (BOLD) contrast induced by administration of the 5-HT-releasing agent,
      fenfluramine, were measured in selected brain regions of halothane-anesthetized
      rats. Initial immunohistochemical measurements of the marker of neural
      activation, Fos, confirmed that in halothane-anesthetized rats fenfluramine (10
      mg/kg i.v.) evoked cellular responses in cortical regions which were attenuated
      by pre-treatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (300
      mg/kg i.p. once daily for 2 days). Fenfluramine-induced Fos was demonstrated in
      numerous glutamatergic pyramidal neurons (Fos/excitatory amino acid carrier 1
      (EAAC1) co-labeled), but also a small number of GABA interneurons (Fos/glutamic
      acid decarboxylase (GAD)(67) colabeled). Fenfluramine (10 mg/kg i.v.) evoked
      changes in BOLD signal intensity in a number of cortical and sub-cortical regions
      with the greatest effects being observed in the nucleus accumbens (-13.0%+/
      2.7%), prefrontal cortex (-10.1%+/-3.2%) and motor cortex (+2.3%+/-1.0%). Pre
      treatment with p-chlorophenylalanine, significantly attenuated the response to
      fenfluramine (10 mg/kg i.v.) in all regions with the exception of the motor
      cortex which showed a trend. These experiments demonstrate that increased 5-HT
      release evokes region-specific changes in the BOLD signal in rats, and that this
      effect is attenuated in almost all regions by 5-HT depletion. These findings
      support the use of fMRI imaging methods as a non-invasive tool to study 5-HT
      function in animal models, with the potential for extension to clinical studies.

PMID- 19174181
TI  - Expression of layer-specific markers in the adult neocortex of BCNU-Treated rat,
      a model of cortical dysplasia.
AB  - The experimental model of cortical dysplasia (CD) obtained by administering
      carmustine (1-3-bis-chloroethyl-nitrosurea [BCNU]) in pregnant rat uterus mimics
      the histopathological abnormalities observed in human CD patients: altered
      cortical layering, and presence of heterotopia and dysmorphic/heterotopic
      neurons. To investigate further the cortical layering disruption and the neuronal
      composition of heterotopia in BCNU-exposed cortex, we analyzed the expression
      pattern of the transcription factors Nurr1, Er81, Ror-beta, and Cux2
      (respectively specific markers of layers VI, V, IV and superficial layers) in the
      cortical areas of BCNU-treated rats by means of in situ hybridization, and
      compared the findings with those observed in adult control rats. Combining in
      situ hybridization and immunohistochemistry we also investigated the origin of
      dysmorphic or heterotopic neurons. The main results of the present study are (i)
      the analysis of cortical layer thickness revealed that the cortical thinning in
      the BCNU model was prevalently restricted to the superficial layers; (ii) in
      cortical and periventricular heterotopia, the prevalent presence of superficial
      layer neurons in the internal areas, and deeper layer neurons in a more
      peripheral region, demonstrated a rudimentary pattern of laminar organization in
      nodule formation; and (iii) the Er81 signal in the dysmorphic and heterotopic
      pyramidal neurons located in layers I/II showed that they belong to layer V.
      These results shed light on the disorganization of the laminar architecture of
      the BCNU model by providing correlations with normal cortical layering and
      revealing the ontogenesis of heterotopia and heterotopic/dysmorphic neurons. They
      also provide strong evidence of the usefulness of layer-specific markers in
      investigating the neuropathology of CD, thus opening up the possibility of
      expanding their application to human neuropathology.

PMID- 19174182
TI  - Unilateral lesion of the nigrostriatal pathway induces an increase of neuronal
      firing of the midbrain raphe nuclei 5-HT neurons and a decrease of their response
      to 5-HT(1A) receptor stimulation in the rat.
AB  - Several studies have shown that the 5-hydroxytryptamine (serotonin, 5-HT) system
      is severely affected after degeneration of nigrostriatal dopaminergic neurons. In
      the present study, we examined the changes in the firing rate and firing pattern
      of the dorsal and median raphe nuclei (DRN and MRN) 5-HT neurons, and the effect
      of the selective 5-HT(1A) receptor agonist (R)-(+)-8-hydroxy-2
      (dipropylamino)tetralin hydrobromide (8-OH-DPAT) and antagonist (N-(2-(4-(2
      methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridylcyclohexane carboxamide maleate
      salt (WAY-100635) on the neuronal firing in rats with 6-hydroxydopamine (6-OHDA)
      lesions of the substantia nigra pars compacta by using extracellular recording.
      The unilateral lesion of the nigrostriatal pathway significantly increased the
      mean firing rate of DRN and MRN 5-HT neurons compared with normal rats, and the
      firing pattern of these neurons also changed significantly towards a more bursty
      one. The lower dose of 8-OH-DPAT, 4 microg/kg (cumulative doses, i.v.),
      completely inhibited the firing activity of all DRN and MRN 5-HT neurons examined
      in normal and sham rats. In contrast to normal and sham rats, only the higher
      doses of 8-OH-DPAT, 128 and 64 microg/kg, completely inhibited the firing rate of
      DRN and MRN 5-HT neurons in 6-OHDA-lesioned rats, respectively. Furthermore, the
      local application of 8-OH-DPAT, 1.5 microg, in the DRN completely inhibited the
      firing rate of 5-HT neurons in normal and sham rats, while having no effect on
      firing rate in the lesioned rats. Altogether, these results indicate that lesion
      of the nigrostriatal pathway leads to hyperactivity of DRN and MRN 5-HT neurons,
      suggesting the implication of the DRN and MRN in the pathophysiology of
      Parkinson's disease, and the decreased response of these 5-HT neurons to 5-HT(1A)
      receptor stimulation, reflecting 5-HT(1A) receptor dysfunction in 6-OHDA-lesioned
      rats.

PMID- 19174183
TI  - Neuronal activation in the CNS during different forms of acute renal failure in
      rats.
AB  - The effect of experimentally induced acute renal failure (ARF) on neuronal cell
      activation was investigated by immunohistochemistry for Fos and Fra-2 in the rat
      brain. ARF in rats was induced by bilateral nephrectomy (BNX), bilateral ureter
      ligature (BUL) and uranyl acetate injection with proper controls (sham-operation
      or saline injections, respectively). To follow the effect of the development of
      ARF, rats were killed 30 and 60 min, and 3, 12, 24 and 72 h after surgery, or 3 h
      to 12 days after uranyl acetate injections. In the BUL and BNX rats, urea and
      creatinine rose markedly in the plasma within 72 h, while in the uranyl acetate
      injected rats the highest levels were observed on the 7th day, followed by a
      marked decline. At each time-point of the three different, experimentally induced
      ARF, the presence of Fos- and/or Fra-2-immunoreactive neurons was determined in
      120 different brain areas and nuclei. In general, the 73 of 120 brain areas that
      showed time and intensity dependent activation in response to ARF can be
      classified into four groups: 1) biogenic amine (noradrenaline, adrenaline,
      histamine and 5-HT) expressing cell groups in the lower brainstem, 2) "stress
      sensitive" forebrain areas, with regard to certain hypothalamic, limbic and
      cortical areas, 3) neuronal cell groups that participate in the central
      regulation of body and brain water and electrolyte homeostasis, including the
      circumventricular organs, and 4) central autonomic cell groups, especially
      visceral sensory cell groups in the brain, which are in primary, secondary or
      tertiary connections with renal afferents. Data presented here indicate that a
      wide variety of neurons in several regulatory mechanisms is affected by ARF
      induced peripheral and central alterations.

PMID- 19174184
TI  - Trophic activity derived from bone marrow mononuclear cells increases peripheral
      nerve regeneration by acting on both neuronal and glial cell populations.
AB  - A rat model of complete sciatic nerve transection was used to evaluate the effect
      of bone marrow mononuclear cells (BMMC) transplanted to the injury site
      immediately after lesion. Rats treated with BMMC had both sensory and motor axons
      reaching the distal stump earlier compared to untreated animals. In addition,
      BMMC transplantation reduced cell death in dorsal root ganglia (DRG) compared to
      control animals. Transplanted BMMC remained in the lesion site for several days
      but there is no evidence of BMMC differentiation into Schwann cells. However, an
      increase in the number of Schwann cells, satellite cells and astrocytes was
      observed in the treated group. Moreover, neutralizing antibodies for nerve growth
      factor (NGF) (but not for brain-derived neurotrophic factor and ciliary-derived
      neurotrophic factor) added to the BMMC-conditioned medium reduced neurite growth
      of sensory and sympathetic neurons in vitro, suggesting that BMMC release NGF,
      improve regeneration of the sciatic nerve in the adult rat and stimulate Schwann
      and satellite cell proliferation or a combination of both.

PMID- 19174185
TI  - Immunohistochemical distribution of AMPA-type label in the pigeon (C. livia)
      hippocampus.
AB  - The avian hippocampal formation (HF) is reported to have a role equivalent to
      that of the mammalian hippocampus, which may involve the glutamatergic system as
      well. In the present paper we offer evidence of the occurrence and distribution
      of the subunits composing AMPA-type glutamate receptors on neurons in the
      hippocampus region of the pigeon brain. The experiment analyzed the
      immunolabeling of glutamate receptor (GluR)(1)(,) GluR(4,) and GluR(2/3) receptor
      subunits in adult pigeons and found consistent evidence that neurons located in
      the five main areas of the avian HF have these AMPA-type subunits, but their
      incidence varies according to position and neuro-type. About 20%-35% of the
      irregular and 35%-70% of the triangular neurons on the lateral and medial "V"
      arms contain GluR(1) and GluR(2/3), while GluR(4) was found only at rounded
      neurons. The majority of the triangular neurons (over 90%) and about half of the
      irregular neurons in the medial area contain GluR(1) and GluR(2/3,) whereas the
      rounded neurons contain primarily GluR(4) (95%). Labeling revealed GluR(1) (40%
      60%) and GluR(2/3) (30%) in the dorsomedial and lateral areas but only in
      irregular neurons, while 60%-80% of the rounded neurons synthesize GluR(4). While
      triangular and irregular neurons appear to match the description of projecting
      neurons, rounded ones seem to participate in local circuits. A discussion of the
      functional significance of the avian HF concentrates on a postulation of the "V"
      arms as equivalent to the dentate gyrus and the dorsomedial area being similar to
      the Ammon's horn.

PMID- 19174186
TI  - Atypical pathways of NF-kappaB activation and aging.
AB  - The eukaryotic transcription factor Nuclear Factor-kappaB (NF-kappaB) is a master
      regulator for inflammatory responses, mediating cellular defense against
      infectious agents and environmental and cellular stress. However, recent evidence
      based studies have demonstrated that constitutive activation of NF-kappaB is a
      ubiquitous phenomenon among various cell types in the aging phenotype,
      contributing deleterious effects that oppose the acutely beneficial effects of NF
      kappaB seen in the inflammatory response. Expression of NF-kappaB with age is
      consistent with elevated levels of inflammatory markers and a pro-inflammatory
      phenotype, manifested in many age-associated diseases. While inducible activating
      mechanisms for NF-kappaB in the innate immune response are well characterized,
      constitutive activation in aging cells warrants further investigation of
      mechanisms collectively called atypical pathways. In this review, we provide a
      comprehensive examination of such NF-kappaB activating mechanisms, including
      mitochondrial dysfunction, endoplasmic stress response, organelle cross-talk,
      secondary messengers and DNA damage. Investigation of mechanisms of NF-kappaB in
      aging as an important marker of cellular stress provides guidance for the
      development of a systems view of cellular aging.

PMID- 19174188
TI  - Genomic and proteomic characterization of a thermophilic Geobacillus
      bacteriophage GBSV1.
AB  - Phages are present wherever life is found, and play roles in many biogeochemical
      and ecological processes. The thermophilic bacteriophages, however, have not been
      well studied. In this study, phage GBSV1 was obtained from a thermophilic
      bacterium Geobacillus sp. 6k51 isolated from a hot spring. GBSV1 contains a
      double-stranded linear DNA of 34,683bp, which encodes 54 putative open reading
      frames (ORFs). Thirty three of these 54 ORFs exhibit sequence similarities to
      genes from 7 species of Geobacillus or Bacillus bacteria, as well as of
      bacteriophages infecting these bacteria. Twenty-two ORFs have been functionally
      annotated based on both their sequence similarities to known genes and predicted
      Pfam protein domains. Five structural proteins of the purified GBSV1 virion have
      been identified by proteomic analyses. Surprisingly, 7 of the GBSV1 ORFs share
      sequence similarities with genes from bacteria relevant to human diseases. This
      is the first report that genes of human disease-inducing bacteria are found in a
      thermophilic phage. It is suggested that thermophilic phages may be the potential
      evolutionary link between thermophiles and human pathogens. The characterization
      of GBSV1 may possibly lead to new insights into virus-host interactions and to a
      better understanding of gene transfers and evolution of life on earth in general.

PMID- 19174187
TI  - Rheostatic signaling by CD44 and hyaluronan.
AB  - Cellular function and adaptive behavior is often driven by signals generated in
      response to the local tissue microenvironment. Cell surface receptors that detect
      changes in extracellular matrix composition and modifications to extracellular
      matrix components, are ideally positioned to provide highly responsive sensors of
      changes in the microenvironment and mediate changes in cellular function required
      to maintain tissue integrity. Receptors can act as "on/off" switches, but
      ligand/receptor complexes that provide "rheostatic" control may be more
      sensitive, provide a more rapid mechanism of control and allow for fine-tuning of
      cellular responses to the microenvironment. Herein, we review evidence that
      transitions in the physiochemical properties of the extracellular
      glycosaminoglycan hyaluronan and in the function of its major receptor, CD44,
      differentially regulate ERK and Rac signal transduction pathways to provide
      critical rheostatic control of mesenchymal cell proliferation.

PMID- 19174189
TI  - Expression, purification, and analyses of glycosylation and disulfide bonds of
      Stereum purpureum endopolygalacturonase I in Pichia pastoris.
AB  - We have succeeded in the expression of Stereum purpureum endopolygalacturonase I
      (EndoPG I) using the Pichia expression system and in purification of the three
      kinds of recombinant EndoPG I, which have one to three sugar chains by using CM52
      column chromatography. The sugar chains which were added to EndoPG I were the M8,
      M9, and/or M10 high-mannose type. The results of LC-MS analysis showed that
      recombinant EndoPG Is were randomly glycosylated at four N-glycosylation sites.
      From the thermal denaturation curves of the recombinant enzymes, it was suggested
      that EndoPG I differing in thermal stability was included in the sample after
      purification. Therefore, we investigated the disulfide bonds of recombinant
      EndoPG I by LC-MS analysis. As a result, peptides without a second or third
      disulfide bond were detected. This result is the first indicating that there are
      incomplete enzymes in terms of disulfide bonds in the Pichia expression system.

PMID- 19174190
TI  - Production of recombinant human lactoferrin in the allantoic fluid of embryonated
      chicken eggs and its characteristics.
AB  - The human iron-binding protein lactoferrin (hLf) has been implicated in a number
      of important physiological pathways, including those regulating immune function
      and tumor growth. In an effort to develop an efficient system for production of
      recombinant hLf (rhLf) that is structurally and functionally equivalent to the
      natural protein, we generated a recombinant CELO (chicken embryo lethal orphan)
      avian adenovirus containing an expression cassette for hLf. Embryonated chicken
      eggs were infected with the generated CELO-Lf virus. rhLf expression was measured
      in the allantoic fluid of infected eggs by ELISA three days later. The level of
      recombinant protein was about 0.8mg per embryo. rhLf was efficiently purified (up
      to 85% yield) from the allantoic fluid of infected eggs using affinity
      chromatography. rhLf produced in the allantoic fluid was characterized in
      comparison with natural hLf (nhLf) purified from human breast milk. SDS-PAGE,
      Western blotting and glycosylation analyzes showed that the recombinant protein
      had similar physical characteristics to nhLf. In addition, we demonstrated that
      the antioxidative and antimicrobial activity of rhLf produced in this system is
      equivalent to that of nhLf. Taken together, these results illustrate the utility
      of the described "recombinant CELO adenovirus-chicken embryo" system for
      production of functionally active rhLf. Efficient production of rhLf with
      accurate structure and function is an important step in furthering investigation
      of Lf as a potential human drug.

PMID- 19174191
TI  - The titerless infected-cells preservation and scale-up (TIPS) method for large
      scale production of NO-sensitive human soluble guanylate cyclase (sGC) from
      insect cells infected with recombinant baculovirus.
AB  - Compounds capable of stimulating soluble guanylate cyclase (sGC) activity might
      become important new tools to treat hypertension. While rational design of these
      drugs would be aided by elucidation of the sGC three-dimensional structure and
      molecular mechanism of activation, such efforts also require quantities of high
      quality enzyme that are challenging to produce. We implemented the titerless
      infected-cells preservation and scale-up (TIPS) methodology to express the
      heterodimeric sGC. In the TIPS method, small-scale insect cell cultures were
      first incubated with a recombinant baculovirus which replicated in the cells. The
      baculovirus-infected insect cells (BIIC) were harvested and frozen prior to cell
      lysis and the subsequent escape of the newly replicated virus into the culture
      supernatant. Thawed BIIC stocks were ultimately used for subsequent scale up. As
      little as 1 mL of BIIC was needed to infect a 100-L insect cell culture, in
      contrast to the usual 1L of high-titer, virus stock supernatants. The TIPS method
      eliminates the need and protracted time for titering virus supernatants, and
      provides stable, concentrated storage of recombinant baculovirus in the form of
      infected cells. The latter is particularly advantageous for virus stocks which
      are unstable, such as those for sGC, and provides a highly efficient alternative
      for baculovirus storage and expression. The TIPS process enabled efficient scale
      up to 100-L batches, each producing about 200mg of active sGC. Careful adjustment
      of expression culture conditions over the course of several 100-L runs provided
      uniform starting titers, specific activity, and composition of contaminating
      proteins that facilitated development of a process that reproducibly yielded
      highly active, purified sGC.

PMID- 19174192
TI  - Time-course study of the early lysosomal responses to pollutants in mussel
      digestive cells using acid phosphatase as lysosomal marker enzyme.
AB  - Lysosomal biomarkers are early warning signals of the biological effects caused
      by environmental pollutants but the promptness of lysosomal responses to
      pollutants has not been investigated yet. This work is aimed to determine the
      response-time of digestive cell lysosomes in mussels exposed to metals and
      hydrocarbons. Mussels, Mytilus galloprovincialis, were exposed, under laboratory
      conditions to Cd and to the water-accommodated fraction of a lubricant oil. One
      mussel per experimental group was sacrificed and processed every hour from 0 h to
      30 h. Changes in AcP activity, immunoreactivity and LMS test based on AcP
      histochemistry, discriminates significantly control and exposed mussels within 5
      h exposure. The present results suggested that after 15-20 h exposure digestive
      cell loss might be accompanied by increased AcP activity (extralysosomal) without
      a parallel increase in the levels of immunoreactive AcP protein, especially after
      Cd-exposure. The reduced labilisation period of lysosomal membrane constitute a
      cost effective early warning signal that, however, is not necessarily correlated
      with the exposure time. The routine application of immunochemical techniques
      deserves more research efforts before its implementation although, these
      techniques are very valuable to understand and interpret correctly lysosomal
      responses to pollutants.

PMID- 19174193
TI  - A 5-year prospective observational study of the outcomes of international
      treatment guidelines for Crohn's disease.
AB  - BACKGROUND & AIMS: Therapeutic strategies for patients with Crohn's disease are
      based on American and European guidelines. High rates of corticosteroid
      dependency and low remission rates are identified as weaknesses of this therapy
      and as justification for early introduction of biologic agents (top-down
      treatment) in moderate/severe Crohn's disease. We reviewed outcomes and
      corticosteroid-dependency rates of patients with moderate-to-severe disease who
      were treated according to the international guidelines. METHODS: Consecutive
      patients (102) newly diagnosed with Crohn's disease in 2000-2002 were identified
      from a prospectively maintained database. Severity of disease was scored using
      the Harvey-Bradshaw Index (HBI). Disease was classified by Montreal
      classification. Five-year follow-up data were recorded. RESULTS: Seventy-two
      patients had moderate/severe disease at diagnosis (HBI >8). Fifty-four (75%) had
      nonstricturing, nonpenetrating disease (B1). Sixty-four (89%) received
      corticosteroids, and 44 (61%) received immunomodulators. Twenty-one patients
      (29%) received infliximab. Thirty-nine patients (54%) required resection surgery.
      At a median of 5 years, 66 of 72 (92%) patients with moderate/severe disease were
      in remission (median HBI, 1). Twenty-five patients (35%) required neither surgery
      nor biologic therapy. CONCLUSIONS: When international treatment guidelines are
      strictly followed, Crohn's disease patients can achieve high rates of remission
      and low rates of morbidity at 5 years. Indiscriminate use of biologic agents
      therefore is not appropriate for all patients with moderate-to-severe disease.

PMID- 19174194
TI  - Expression pattern of the expanded noggin gene family in the planarian Schmidtea
      mediterranea.
AB  - Noggin genes are mainly known as inhibitors of the Bone Morphogenetic Protein
      (BMP) signalling pathway. Noggin genes play an important role in various
      developmental processes such as axis formation and neural differentiation. In
      vertebrates, inhibition of the BMP pathway is usually carried out together with
      other inhibitory molecules: chordin and follistatin. Recently, it has been shown
      in planarians that the BMP pathway has a conserved function in the maintenance
      and re-establishment of the dorsoventral axis during homeostasis and
      regeneration. In an attempt to further characterize the BMP pathway in this model
      we have undertaken an in silico search of noggin genes in the genome of Schmidtea
      mediterranea. In contrast to other systems in which between one and four noggin
      genes have been reported, ten genes containing a noggin domain are present in S.
      mediterranea. These genes have been classified into two groups: noggin genes (two
      genes) and noggin-like genes (eight genes). Noggin-like genes are characterized
      by the presence of an insertion of 50-60 amino acids in the middle of the noggin
      domain. Here, we report the characterization of this expanded family of noggin
      genes in planarians as well as their expression patterns in both intact and
      regenerating animals. In situ hybridizations show that planarian noggin genes are
      expressed in a variety of cell types located in different regions of the
      planarian body.

PMID- 19174195
TI  - Physiological basis to climb Mt. Everest in one day.

PMID- 19174196
TI  - Atmospheric pressure photoionization for coupling liquid-chromatography to mass
      spectrometry: a review.
AB  - This review presents the state-of-the-art techniques that couple liquid
      chromatography (LC) and mass spectrometry (MS) via atmospheric pressure
      photoionization (APPI). The different ionization mechanisms are discussed as well
      as the influence of the mobile phase composition, the nature of the dopant, etc.
      A comparison with other ionization sources, such as electrospray ionization (ESI)
      and atmospheric pressure chemical ionization (APCI), is reported, and the
      combination of APPI with these sources is also discussed. Several applications,
      covering the time period of 2005-2008, for the analysis of drugs, lipids, natural
      compounds, pesticides, synthetic organics, petroleum derivatives, and other
      substances are presented.

PMID- 19174197
TI  - Nanocrystalline Ni0.6Zn0.4Fe2O4: a novel semiconducting material for ethanol
      detection.
AB  - The structure and crystal phase of the nanocrystalline powders of Ni(1
      x)Zn(x)Fe(2)O(4) (0<or=x<or=0.5) mixed ferrite, synthesized by ethylene glycol
      mediated citrate sol-gel method, were characterized by X-ray diffraction and
      microstructure by transmission electron microscopy. Further studies by Fourier
      transform infrared spectroscopy were also conducted. Moreover, DC electrical
      properties of the prepared nanoparticles were studied by DC conductivity
      measurements. The response of prepared Ni(1-x)Zn(x)Fe(2)O(4) mixed ferrites to
      different reducing gases (ethanol, hydrogen sulfide, ammonia, hydrogen and
      liquefied petroleum gas) was investigated. In particular, Ni(0.6)Zn(0.4)Fe(2)O(4)
      composition exhibited high response to 100 ppm ethanol gas at 300 degrees C.
      Incorporation of palladium further improved the response, selectivity and
      response time of Ni(0.6)Zn(0.4)Fe(2)O(4) to ethanol gas with the blue shift in
      the operating temperature by 25 degrees C.

PMID- 19174198
TI  - A novel molecularly imprinted sensor for selectively probing imipramine created
      on ITO electrodes modified by Au nanoparticles.
AB  - A sensitive molecularly imprinted electrochemical sensor was created for
      selective detection of a tricyclic antidepressant imipramine by combination of Au
      nanoparticles (Au-NPs) with a thin molecularly imprinted film. The sensor was
      fabricated onto the indium tin oxide (ITO) electrode via stepwise modification of
      Au-NPs by self-assembly and a thin film of molecularly imprinted polymers (MIPs)
      via sol-gel technology. It was observed that the molecularly imprinted film
      displayed excellent selectivity towards the target molecule imipramine.
      Meanwhile, the introduced Au-NPs exhibited noticeable catalytic activities
      towards imipramine oxidation, which remarkably enhanced the sensitivity of the
      imprinted film. Due to such combination, the as-prepared sensor responded quickly
      to imipramine, within only 1 min of incubation. The differential voltammetric
      anodic peak current was linear to the logarithm of imipramine concentration in
      the range from 5.0x10(-6) to 1.0x10(-3) mol L(-1), and the detection limits
      obtained was 1.0x10(-9) mol L(-1). This method proposed was successfully applied
      to the determination of imipramine in drug tablets, and proven to be reliable
      compared with conventional UV method. These results reveal that such a sensor
      fulfills the selectivity, sensitivity, speed and simplicity requirements for
      imipramine detection, and provides possibilities of clinical application in
      physiological fluids.

PMID- 19174199
TI  - Microwave-assisted extraction for qualitative and quantitative determination of
      brominated flame retardants in styrenic plastic fractions from waste electrical
      and electronic equipment (WEEE).
AB  - A fast method for the determination of brominated flame retardants (BFRs) in
      styrenic polymers using microwave-assisted extraction (MAE) and liquid
      chromatography with UV detection (HPLC-UV) was developed. Different extraction
      parameters (extraction temperature and time, type of solvent, particle size) were
      first optimised for standard high-impact polystyrene (HIPS) samples containing
      known amounts of tetrabromobisphenol A (TBBPA) and decabromodiphenyl ether (Deca
      BDE). Complete extraction of TBBPA was achieved using a combination of polar/non
      polar solvent system (isopropanol/n-hexane) and high extraction temperatures (130
      degrees C). Lower extraction yields were, however, obtained for Deca-BDE, due to
      its high molecular weight and its non-polar nature. The developed method was
      successfully applied to the screening of BFRs in standard plastic samples from
      waste electrical and electronic equipment (WEEE); TBBPA could be fully recovered,
      and Deca-BDE could be identified, together with minor order polybrominated
      diphenyl ether (PBDE) congeners.

PMID- 19174200
TI  - Fast and selective determination of triterpenic compounds in olive leaves by
      liquid chromatography-tandem mass spectrometry with multiple reaction monitoring
      after microwave-assisted extraction.
AB  - A method for fast and selective determination of the main triterpenic compounds
      present in olive leaves - oleanolic, ursolic and maslinic acids as triterpenic
      acids and, uvaol and erythrodiol as triterpenic dialcohols - is reported here.
      Quantitative isolation of the analytes has been accomplished in 5min by microwave
      assistance using ethanol as extractant. Due to the medium polarity of triterpenic
      acids and dialcohols, different ethanol-water ratios were tested in order to
      select the optimum extractant composition for their solubilisation. Microwave
      assistance provided a significant shortening of the leaching time as compared to
      conventional procedures by maceration, which usually requires at least 5h. After
      extraction, determination was carried out by liquid chromatography-tandem mass
      spectrometry (LC-MS-MS) with a triple quadrupole (qQq) mass detector without any
      clean-up step prior to chromatographic analysis. Highly selective identification
      of triterpenes was confirmed by multiple reaction monitoring (MRM) using the most
      representative transitions from the precursor ion to the different product ions,
      while the most sensitive transitions were used for MS-MS quantitation. Total
      analysis performed in 25 min enables the characterization of a fraction with
      particular interest in the pharmacological area.

PMID- 19174201
TI  - A new electrochemical method for trace water determination in methanol.
AB  - A new electrochemical method for the determination of trace water in methanol has
      been developed. This method is based on the effect, that a minor change in the
      water content affects the value of conductivity measured for dissolved in the
      solutions electrolyte. The conductivity measurements were performed for four
      inorganic salts, i.e. NaCl, KCl, RbCl, and CsCl in solutions with different
      amounts of water traces in methanol and the calibration curves for three of them
      were determined. With the exception of cesium chloride the high values of
      correlation coefficients for the regression lines as well as low limits of
      detection were achieved in all cases which indicates that this method is a useful
      tool for the determination of the trace amounts of water in methanol.

PMID- 19174202
TI  - Arsenic speciation in natural water samples by coprecipitation-hydride generation
      atomic absorption spectrometry combination.
AB  - A speciation procedure for As(III) and As(V) ions in environmental samples has
      been presented. As(V) was quantitatively recovered on aluminum hydroxide
      precipitate. After oxidation of As(III) by using dilute KMnO(4), the developed
      coprecipitation was applied to determination of total arsenic. Arsenic(III) was
      calculated as the difference between the total arsenic content and As(V) content.
      The determination of arsenic levels was performed by hydride generation atomic
      absorption spectrometry (HG-AAS). The analytical conditions for the quantitative
      recoveries of As(V) including pH, amount of aluminum as carrier element and
      sample volume, etc. on the presented coprecipitation system were investigated.
      The effects of some alkaline, earth alkaline, metal ions and also some anions
      were also examined. Preconcentration factor was calculated as 25. The detection
      limits (LOD) based on three times sigma of the blank (N: 21) for As(V) was 0.012
      microg L(-1). The satisfactory results for the analysis of arsenic in NIST SRM
      2711 Montana soil and LGC 6010 Hard drinking water certified reference materials
      for the validation of the method was obtained. The presented procedure was
      successfully applied to real samples including natural waters for arsenic
      speciation.

PMID- 19174203
TI  - Chemometric-assisted MIP-optosensing system for the simultaneous determination of
      monoamine naphthalenes in drinking waters.
AB  - In the present work a chemometric-assisted molecularly imprinted polymer (MIP)
      fluorescence optosensing system has been developed for determining monoamines
      naphthalene compounds in drinking waters. The use of chemometrics for processing
      flow injection analysis with MIP fluorescence optosensor data allowed the
      simultaneous determination of the principal monoamine naphthalene compounds 1
      naphthylamine (1-NA) and 2-naphthylamine (2-NA) even in presence of potential
      interferent 1-naphthalenemethylamine (1-NMA). Classical chemometrics tools such
      as partial least-squares (PLS-1), as well as second-order algorithms like
      multiway PLS (N-PLS) and unfolded PLS (U-PLS), were successfully applied,
      assisting fluorescence emission spectra at a fixed excitation wavelength or
      excitation-emission fluorescence matrices (EEM), respectively, when interferents
      are considered in the calibration set. The combinations of both N-PLS and U-PLS
      with residual bilinearization (RBL), achieving the second-order advantage, were
      satisfactory applied for the simultaneous determination of the main monoamine
      naphthalene compounds in drinking water, in the presence of a potential
      interferent without sample pretreatment, even when the later is not modeled in
      calibration set. Predictive ability, accuracy, figures of merit, as well as
      advantages and disadvantages of the different strategies were discussed.

PMID- 19174204
TI  - Amperometric tape ion sensors for cadmium(II) ion analysis.
AB  - This paper describes a novel tape platform ion sensing methodology specific to
      the detection of cadmium(II) ions in aqueous solution based on assisted ion
      transfer reactions across a polarized water/organic gel micro-interface. The tape
      ion sensors were constructed to incorporate the micro-water/polyvinylchloride-2
      nitrophenylethyl ether (PVC-NPOE) gel interfaces referred to as ionodes. The
      sensors have overall thicknesses less than 300 microm, allowing their packaging
      in a disposable tape format. The detection methodology is based on the selective
      assisted transfer of the cadmium ion in aqueous phase by ETH 1062 present in the
      PVC-NPOE gel layer and was first investigated using cyclic voltammetry.
      Quantitative analysis of cadmium(II) ions in aqueous solution using the tape
      sensors was then conducted under stop-flow conditions. Detection limits as low as
      20 ppb (178 nM) for Cd(II) ions in very small volumes as low as a single 20
      microl droplet without any sample preconcentration was achieved in an analysis
      time of approximately 20s, which could be easily employed for the direct
      measurement of Cd(II) ion levels in various field applications. The tape ion
      sensor can also be used in a flow-cell geometry to preconcentrate Cd(II) ions
      from aqueous samples and further improve the detection limit.

PMID- 19174205
TI  - Silk fibroin as a sorbent for on-line extraction and preconcentration of copper
      with detection by electrothermal atomic absorption spectrometry.
AB  - Silk fibroin is a kind of polypeptide with functional amino acids in its
      structure. The electric charges in its molecular chains originating from the
      dissociation of acidic groups, i.e., hydroxyl, phenol and carboxyl, provide vast
      potentials for the retention of metal species of interest. In this study, the
      selective retention of Cu(2+) with silk fibroin at pH 6.0 was investigated and a
      novel on-line procedure for separation/preconcentration of Cu(2+) from complex
      sample matrices was thus developed by using a sequential injection system with an
      electrothermal atomic absorption spectrometry. A novel concept of enrichment
      index (EI), i.e., defined as enrichment factor (EF) obtained by consuming unity
      of sample volume (ml), was proposed for evaluating the enrichment efficiency of a
      flow-based preconcentration procedure. With a sampling volume of 900 microl, an
      EI of 30.3 (EF=27.3) was achieved, which was much improved as compared to that of
      reported procedures. A detection limit of 8.0 ng l(-1) was achieved within a
      linear range of 0.025-1.5 microg l(-1) along with a precision of 2.2% R.S.D. at
      0.5 microg l(-1). The practical applicability of this procedure was validated by
      analyzing a certified reference material of riverine water (GBW08608) and a
      certified reference material of seawater (NASS-5) achieving satisfactory
      agreements between the certified and the obtained values. A spiking recovery was
      also performed by using a cave water sample.

PMID- 19174206
TI  - An electrochemiluminescent biosensor for glucose based on the
      electrochemiluminescence of luminol on the nafion/glucose
      oxidase/poly(nickel(II)tetrasulfophthalocyanine)/multi-walled carbon nanotubes
      modified electrode.
AB  - A poly(nickel(II) tetrasulfophthalocyanine)/multi-walled carbon nanotubes
      composite modified electrode (polyNiTSPc/MWNTs) was fabricated by
      electropolymerization of NiTSPc on MWNTs-modified glassy carbon electrode (GCE).
      The modified electrode was found to be able to greatly improve the emission of
      luminol electrochemiluminescence (ECL) in a solution containing hydrogen
      peroxide. Glucose oxidase (GOD) was immobilized on the surface of
      polyNiTSPc/MWNTs modified GC electrode by Nafion to establish an ECL glucose
      sensor. Under the optimum conditions, the linear response range of glucose was
      1.0x10(-6) to 1.0x10(-4) mol L(-1) with a detection limit of 8.0x10(-8) mol L(-1)
      (defined as the concentration that could be detected at the signal-to-noise ratio
      of 3). The ECL sensor showed an outstanding well reproducibility and long-term
      stability. The established method has been applied to determine the glucose
      concentrations in real serum samples with satisfactory results.

PMID- 19174207
TI  - Determination of strontium and simultaneous determination of strontium oxide,
      magnesium oxide and calcium oxide content of Portland cement by derivative ratio
      spectrophotometry.
AB  - A derivative spectrophotometric method has been developed for the determination
      of strontium in Portland cement. The method is applied successfully for the
      simultaneous determination of SrO, MgO and CaO. It is based on the use of
      Alizarin Complexone (AC) as a complexing agent and measurement of the derivative
      ratio spectra of the analytes. Interferences of manganese(II) and zinc(II) were
      eliminated by precipitation. The validity of the method was examined by analyzing
      several Standard Reference Material (SRM) Portland cement samples. The strontium
      complex formed at pH 9.5 allows precise and accurate determination of strontium
      over the concentration range of 1.5-18 mg L(-1) of strontium. The MDL (at 95%
      confidence level) was found to be 25 ng mL(-1) for strontium in National
      Institute of Standards and Technology (NIST) cement samples using the proposed
      method.

PMID- 19174208
TI  - Speciation of inorganic arsenic in a sequential injection dual mini-column system
      coupled with hydride generation atomic fluorescence spectrometry.
AB  - The separation and speciation of inorganic arsenic(III) and arsenic(V) are
      facilitated by employing a novel sequential injection system incorporating two
      mini-columns followed by detection with hydride generation atomic fluorescence
      spectrometry. An octadecyl immobilized silica mini-column is used for selective
      retention of the complex between As(III) and APDC, while the sorption of As(V) is
      readily accomplished by a 717 anion exchange resin mini-column. The retained
      As(III)-PDC complex and As(V) are effectively eluted with a 3.0 mol L(-1)
      hydrochloric acid solution as stripping reagent, which well facilitates the
      ensuing hydride generation process via reaction with tetrahydroborate. With a
      sampling volume of 1.0 mL and an eluent volume of 100 microL for both species,
      linear ranges of 0.05-1.5 microg L(-1) for As(III) and 0.1-1.5 microg L(-1) for
      As(V) are obtained, along with enrichment factors of 7.0 and 8.2, respectively.
      Precisions of 2.8% for As(III) and 2.9% for As(V) are derived at the
      concentration level of 1.0 microg L(-1). The practical applicability of the
      procedure has been demonstrated by analyzing a certified reference material of
      riverine water (SLRS-4), in addition to spiking recovery in a lake water sample
      matrix.

PMID- 19174209
TI  - Selective determination of doxorubicin and doxorubicinol in rat plasma by HPLC
      with photosensitization reaction followed by chemiluminescence detection.
AB  - A highly sensitive and selective high-performance liquid chromatography (HPLC)
      method was developed for the determination of doxorubicin (DXR) and its
      metabolite doxorubicinol (DXR-ol) in rat plasma. The method was based on
      photosensitization reaction followed by peroxyoxalate chemiluminescence detection
      (PO-CL). DXR and DXR-ol that were fluorescent quinones, served as a
      photosensitizer in the presence of a hydrogen atom donor such as ethanol under
      aerobic conditions to produce hydrogen peroxide. Then the generated hydrogen
      peroxide and DXR or DXR-ol were monitored through PO-CL reaction by mixing with
      aryloxalate as a single post-column reagent that enabled highly selective and
      sensitive determination of DXR and DXR-ol. The separation of DXR and DXR-ol by
      HPLC was accomplished isocratically on an ODS column within 15 min. The method
      involves a simple one step protein precipitation by methanol and a sample size of
      50-microL was sufficient. Besides, it can detect accurately the low plasma
      concentrations. The detection limits (signal-to-noise ratio=3) were 4.5 and 3.8
      fmol for DXR and DXR-ol, respectively. The percentage recovery was found to be
      90.7-102.4% and the inter- and intra-assay RSD values in rat plasma were 2.5
      8.9%. The method has been successfully used to study pharmacokinetic profiles of
      DXR and DXR-ol in rats after a single-dose of DXR.

PMID- 19174210
TI  - A novel stir bar sorptive extraction coating based on monolithic material for
      apolar, polar organic compounds and heavy metal ions.
AB  - In this study, a novel stir bar sorptive extraction (SBSE) based on monolithic
      material (SBSEM) was prepared. The monolithic material was obtained by in situ
      copolymerization of vinylpyrrolidone and divinylbenzene in the presence of a
      porogen solvent containing cyclohexanol and 1-dodecanol with
      azobisisobutyronitrile as initiator. The influences of polymerization conditions
      on the extraction efficiencies were investigated, using phenol and p-nitrophenol
      as detected solutes. The monolithic material was characterized by various
      techniques, such as elemental analysis, scanning electron microscopy, mercury
      intrusion porosimetry, infrared spectroscopy. Polycyclic aromatic hydrocarbons
      were used to investigate the extraction efficiencies of SBSEM for apolar
      analytes. Hormones, aromatic amines and phenols were selected as test analytes to
      investigate the extraction efficiencies of SBSEM for weakly and strongly polar
      compounds. The results showed that the new SBSEM could enrich the above-mentioned
      organic compounds effectively. It is worthy to mention that the SBSEM can enrich
      some heavy metal ions, such as Cu(2+), Pb(2+), Cr(3+) and Cd(2+), through
      coordination adsorption. To our best knowledge, that is the first to use SBSE to
      enrich heavy metal ions.

PMID- 19174211
TI  - Artificial neural networks in analysis of indinavir and its degradation products
      retention.
AB  - Artificial neural networks (ANN) are biologically inspired computer programs
      designed to simulate the way in which the human brain processes the information.
      In the past few years, coupling of experimental design (ED) and ANN became useful
      tool in the method optimization. This paper presents the application of ED-ANN in
      analysis of chromatographic behavior of indinavir and its degradation products.
      According to preliminary study, full factorial design 2(4) was chosen to set
      input variables for network training. Experimental data (inputs) and results for
      retention factors from experiments (outputs) were used to train the ANN with aim
      to define correlation among variables. For networks training multi-layer
      perceptron (MLP) with back propagation (BP) algorithm was used. Network with the
      lowest root mean square (RMS) had 4-8-3 topology. Predicted data were in good
      agreement with experimental data (correlation was higher than 0.9713 for training
      set). Regression statistics confirmed good ability of trained network to predict
      compounds retention.

PMID- 19174212
TI  - Uncertainty due to volumetric operations is often underestimated.
AB  - Fifteen international titration standards were evaluated to determine minimum and
      maximum combined standard uncertainties. Assuming most thorough performance of
      the analyses revealed minimum values, whereas maximum values of uncertainty were
      obtained assuming that the analyses had been done under high time pressure.
      Minimum and maximum uncertainties were compared with the corresponding
      reproducibility standard deviations. Since the combined standard uncertainty is
      expected to lie between the reproducibility standard deviation and the maximum
      combined standard uncertainty, realistic standard uncertainties of individual
      influence quantities of volumetric and weighing procedures could be calculated.
      This top-down approach revealed up to 4 times higher uncertainties for volumetric
      operations compared to the bottom-up approach according to the current
      literature. Hence, uncertainty due to volumetric operations is obviously strongly
      underestimated. The present study additionally contains a ranking of the
      contributions to the uncertainty of titrimetric results.

PMID- 19174213
TI  - Direct electrochemistry and electrocatalysis of horseradish peroxidase
      immobilized in hybrid organic-inorganic film of chitosan/sol-gel/carbon
      nanotubes.
AB  - A hybrid organic-inorganic nanocomposite film of chitosan/sol-gel/multi-walled
      carbon nanotubes was constructed for the immobilization of horseradish peroxidase
      (HRP). This film was characterized by scanning electron microscopy. Direct
      electron transfer (DET) and bioelectrocatalysis of HRP incorporated into the
      composite film were investigated. The results indicate that the film can provide
      a favorable microenvironment for HRP to perform DET on the surface of glassy
      carbon electrodes with a pair of quasi-reversible redox waves and to retain its
      bioelectrocatalytic activity toward H(2)O(2).

PMID- 19174214
TI  - Iron (III) porphyrin bearing 2,6-di-tert-butylphenol pendants deposited onto gold
      electrodes for amperometric determination of L-histidine.
AB  - A sensitive amperometric sensor for determination of L-histidine was developed
      using gold electrode modified with Fe(III)-porphyrin bearing three 2,6-di-tert
      butylphenol groups and one palmitoyl chain. Two methods of electrode modification
      were applied: direct chemisorption and embedment into dodecanethiol monolayer.
      Both types of electrodes were used for detection of L-histidine using Osteryoung
      square-wave voltammetry. The sensitivity of sensors presented towards L-histidine
      depends on the method of electrode modification. The detection limits observed
      for the electrodes incorporating with Fe(III)-porphyrin host by embedment and
      chemisorption were in 1 and 100 nM ranges, respectively. In addition, the
      determination of L-histidine with electrode modified by embedment technique was
      more precise, in comparison to that obtained by the direct chemisorption.
      Applicability of gold electrodes modified with Fe(III)-porphyrin for the direct
      electrochemical determination of L-histidine was demonstrated using the
      artificial matrix mimicking human serum.

PMID- 19174215
TI  - Imaging of nutrient elements in the leaves of Elsholtzia splendens by laser
      ablation inductively coupled plasma mass spectrometry (LA-ICP-MS).
AB  - Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used
      for the quantitative imaging of nutrient elements (such as K, Mg, Mn, Cu, P, S
      and B) in the leaves of Elsholtzia splendens. The plant leaves were scanned
      directly with a focused Nd:YAG laser in the laser ablation chamber. The ablated
      material was transported with argon as carrier gas to a quadrupole-based ICP-MS
      (ICP-QMS), and the ion intensities of (39)K(+), (24)Mg(+), (55)Mn(+), (63)Cu(+),
      (31)P(+), (34)S(+) and (11)B(+) were measured by ICP-QMS to study the
      distribution of the elements of interest. The imaging technique using LA-ICP-MS
      on plant leaves does not require any sample preparation. Carbon ((13)C(+)) was
      used as an internal standard element to compensate for the difference in the
      amount of material ablated. Additional experiments were performed in order to
      study the influence of the water content of the analyzed leaves on the intensity
      signal of the analyte. For quantification purposes, standard reference material
      (NIST SRM 1515 Apple Leaves) was selected and doped with standard solutions of
      the analytes within the concentration range of 0.1-2000 mg L(-1). The synthetic
      laboratory standards together with the samples were measured by LA-ICP-MS. The
      shape and structure of the leaves was clearly given by LA-ICP-MS imaging of all
      the elements measured. The elemental distribution varied according to the
      element, but with a high content in the veins for all the elements investigated.
      Specifically, Cu was located uniformly in the mesophyll with a slightly higher
      concentration in the main vein. High ion intensity was measured for S with a high
      amount of this element in the veins similar to the images of the metals, whereas
      most of the B was detected at the tip of the leaf. With synthetic laboratory
      standard calibration, the concentrations of elements in the leaves measured by LA
      ICP-MS were between 20 microg g(-1) for Cu and 14,000 microg g(-1) for K.

PMID- 19174216
TI  - Determination of polybrominated diphenyl ethers in human hair by gas
      chromatography-mass spectrometry.
AB  - A rapid analytical method has been developed for the determination of
      polybrominated diphenyl ethers (PBDEs) in human hair. PBDEs were determined by
      gas chromatography with electron ionization mass spectrometric detection in the
      selected ion monitoring mode (GC-MS-SIM). A 200mg amount of hair samples was
      overnight digested in 3N HCl and then PBDEs extracted with n-hexane. After clean
      up of extracts in a Florisil column, PBDEs were analyzed by GC-MS. The method has
      been validated by spiking human hair at five concentration levels, in the range
      from 5 to 25 ng/g for most compounds, and PBDEs were quantified using labelled
      compounds as internal standards. Recoveries of PBDEs were higher than 90%,
      repeatability was equal or lower than 12.5%, and reproducibility lower than 14%,
      expressed as relative standard deviation (RSD). Limits of detection (LOD) were in
      the range 0.08-0.9 ng/g and limits of quantification (LOQ) were between 0.27 and
      3.0 ng/g. This method was applied to the determination of PBDEs in hair samples
      from 16 individuals and 5 PBDE congeners were detected in most of the samples.
      BDE-209 was the dominant compound found, followed by BDE-47, BDE-99, BDE-100, and
      BDE-190. BDE-209 was found in 12 out of 16 hair samples, and the total levels of
      PBDEs ranged from 1.4 to 19.9 ng/g.

PMID- 19174217
TI  - Flow injection on-line displacement/solid phase extraction system coupled with
      flame atomic absorption spectrometry for selective trace silver determination in
      water samples.
AB  - A novel flow injection (FI) on-line displacement solid phase extraction
      preconcentration and/or separation method coupled with FAAS in order to minimize
      interference from other metals was developed for trace silver determination. The
      proposed method involved the on-line formation and subsequently pre-sorption of
      lead diethyldithiocarbamate (Pb-DDTC) into a column packed with PTFE-turnings.
      The preconcentration and/or separation of the Ag(I) took place through a
      displacement reaction between Ag(I) and Pb(II) of the pre-sorbed Pb-DDTC.
      Finally, the retained analyte was eluted with isobutyl methyl ketone (IBMK) and
      delivered directly to nebulizer for measuring. Interference from co-existing ions
      with lower DDTC complex stability in comparison with Pb-DDTC, was eliminated
      without need for any masking reagent. With 120 s of preconcentration time at a
      sample flow rate of 7.6 mL min(-1), an enhancement factor of 110 and a detection
      limit (3s) of 0.2 microg L(-1) were obtained. The precision (RSD, n=10) was 3.1%
      at the 10 mug L(-1) level. The developed method was successfully applied to trace
      silver determination in a variety of environmental water samples and certified
      reference material.

PMID- 19174218
TI  - Fast analysis of catecholamine metabolites MHPG and VMA in human plasma by HPLC
      with fluorescence detection and a novel SPE procedure.
AB  - A fast and sensitive high-performance liquid chromatographic method has been
      developed for the determination in human plasma of MHPG (3-methoxy-4
      hydroxyphenylethylenglycol) and VMA (vanillyl mandelic acid), the main
      metabolites of epinephrine and norepinephrine. Analyses were carried out at 325
      nm while exciting at 285 nm on a reversed-phase column (Atlantis C18, 150 mm x
      4.6 mm I.D., 5 microm) using a mobile phase composed of 2% methanol and 98%
      aqueous citrate buffer at pH 3.0. A careful solid-phase extraction procedure,
      based on mixed-mode reversed-phase - strong anion exchange Oasis cartridges (MAX,
      30 mg, 1 mL), was developed for the pre-treatment of plasma samples. Extraction
      yields were satisfactory, always higher than 90%. Calibration curves were linear
      over the 0.2-40.0 ng mL(-1) concentration range for MHPG and over the 0.5-40.0 ng
      mL(-1) concentration range for VMA. The method was successfully applied to plasma
      samples of former drug users undergoing detoxification therapy and subjects "at
      risk" of developing drug addiction.

PMID- 19174219
TI  - Comparison of ultrasonic and pressurized liquid extraction for the analysis of
      polycyclic aromatic compounds in soil samples by gas chromatography coupled to
      tandem mass spectrometry.
AB  - A pressurized liquid extraction (PLE) method has been optimized for the
      determination of polycyclic aromatic hydrocarbons (PAHs) in soil samples and it
      was compared with ultrasonic extraction. The extraction step was followed by gas
      chromatography-triple quadrupole mass spectrometry (GC-QqQ-MS/MS) analysis.
      Parameters such as type of solvent, extraction time, extraction temperature and
      number of extractions were optimized. There were no significant differences among
      the two extraction methods although better extraction efficiencies were obtained
      when PLE was used, minimizing extraction time and solvent consumption. PLE
      procedure was validated, obtaining limits of detection (LODs) ranging from 0.02
      to 0.75 microg kg(-1) and limits of quantification (LOQs) ranging from 0.07 to
      2.50 microg kg(-1) for the selected PAHs. Recoveries were in the range of 59
      110%, except for naphthalene, which was the most volatile PAH. Finally, the
      method was applied to real soil samples from Southeast of Spain. PAHs
      concentrations were low, and phenanthrene, pyrene, fluorene, benzo[a]pyrene and
      chrysene were the most frequently detected analytes in the samples.

PMID- 19174220
TI  - Surface IR applied to rapid and direct immunosensing of environmental pollutants.
AB  - This paper describes the elaboration of a model immunosensor monitored by
      polarization modulation reflection absorption infrared spectroscopy (PM-RAIRS)
      and quartz crystal microbalance (QCM-D), as well as its reactivity using PM-RAIRS
      as transduction technique. To prove its relevance, this immunosensor was applied
      to the detection of benzo[a]pyrene (BaP), a carcinogenic polycylic aromatic
      hydrocarbon. Very few immunoassays, and even fewer immunosensors, have been
      described for the assay of BaP, making it an interesting target for analytical
      device development. The PM-RAIRS immunosensor was constructed on planar gold
      coated sensors functionalized with cystamine then glutaraldehyde. Antibodies were
      immobilized through their affinity to protein G, covalently coupled to the
      aldehyde layer. In a first stage, a model mouse IgG was utilized to optimize the
      elaboration parameters; then, a monoclonal anti-PAH antibody was used and
      detection tests were performed, monitored by PM-RAIRS. The successive
      functionalization steps were monitored by PM-RAIRS and QCM-D. The binding of the
      proteins to gold surface, their saturation coverages and association constants,
      as well as their capture efficiencies were discussed. BaP capture by the antibody
      layer was evidenced by the appearance of a new nu(C-H) band at 3039 cm(-1)
      typical of aromatic C-H bonds. The integrated area of this band varied linearly
      with the BAP concentration within the range of tested concentrations, with a
      limit of detection close to 3 microM. This represents the first example of
      direct, label-free immunodetection of a low molecular weight molecule by PM-RAIRS
      transduction. The simplicity and the rapid response of this IR sensor make it
      already very worthwhile to preliminary on-site measurements.

PMID- 19174221
TI  - Pore-functionalized polymer membranes for preconcentration of heavy metal ions.
AB  - Functionalized membranes containing carboxylate, phosphate and sulfonate groups
      were prepared by UV-initiator induced graft polymerization of the functional
      monomer (acrylic acid, ethylene glycol methacrylate phosphate (EGMP) and 2
      acrylamido-2-methyl-1-propane sulfonic acid) with a crosslinker
      (methylenebisacrylamide) in the pores of poly(propylene) host membranes. The
      functionalized membranes thus obtained were characterized by gravimetry, FTIR
      spectroscopy, radiotracers and scanning electron microscopy for the degree of
      grafting and water uptake, presence of functional groups, ion-exchange capacity,
      and physical structure of the membranes, respectively. The uptakes of Cs(+),
      Ag(+), Sr(2+), Cd(2+), Hg(2+), Zn(2+), Eu(3+), Am(3+), Hf(4+) and Pu(4+) ions in
      the functionalized membranes were studied as a function of acidity of the
      equilibrating aqueous solution. Among the functionalized membranes prepared in
      the present work, the EGMP-grafted membrane (with phosphate groups) showed acid
      concentration dependent selectivity towards multivalent metal ions like Eu(3+),
      Am(3+), Hf(4+) and Pu(4+). The solvent extraction studies of EGMP monomer in
      methyl isobutyl ketone (MIBK) solvent indicated that divalent and trivalent metal
      ions form complexes with EGMP in 1:2 proportion, but the distribution
      coefficients of trivalent metal ions were significantly higher that for the
      divalent ions. The uptakes of Eu(3+) ions in monomeric EGMP (dissolved in MIBK)
      and polymeric EGMP (in the forms of crosslinked gel and membrane) were studied as
      a function of concentration of H(+) ions in the equilibrating solution. This
      study indicated that polymeric EGMP has better binding ability towards Eu(3+) as
      compared to monomeric EGMP. The variation of distribution coefficients of
      Eu(3+)/Am(3+) in gel and membrane as a function of H(+) ion concentration in the
      equilibrating aqueous solution indicated that ionic species held in the membrane
      and gel were not same. These results indicated that proximity of functional
      groups (phosphate) plays an important role in metal ion binding with polymeric
      EGMP.

PMID- 19174222
TI  - Development of a method for the analysis of seven banned azo-dyes in chilli and
      hot chilli food samples by pressurised liquid extraction and liquid
      chromatography with electrospray ionization-tandem mass spectrometry.
AB  - An automated, confirmatory and sensitive procedure has been developed and
      validated for the determination of Sudan (I-IV), Sudan Orange G, Sudan Red 7B and
      Para Red in hot chilli food samples. The proposed method includes pressurised
      liquid extraction (PLE) with acetone, gel permeation chromatography (GPC) clean
      up and detection by liquid chromatography (LC) coupled to electrospray ionization
      in positive mode tandem mass spectrometry (ESI-MS-MS). The main parameters
      affecting the performance of the different ionization sources and PLE parameters
      were previously optimised using statistical design of experiments (DOE). The
      method was in-house validated on chilli powder and chilli meat. Linear
      calibrations were obtained with correlation coefficients R(2)>0.999. The limits
      of detection (LOD) and quantification (LOQ) of the method were in the ranges of
      0.002-0.012 ng g(-1) and 0.006-0.036 ng g(-1), respectively for chilli powder.
      The decision limit and detection capability were between 0.005-0.022 ng g(-1) and
      0.007-0.026 ng g(-1), respectively for chilli meat. Recoveries ranged from 94% to
      105%. The applicability of the method to the determination of azo-dyes in hot
      chilli products was demonstrated.

PMID- 19174223
TI  - Indicator-based and indicator-free magnetic assays connected with disposable
      electrochemical nucleic acid sensor system.
AB  - An indicator-based and indicator-free magnetic assays connected with a disposable
      pencil graphite electrode (PGE) were successfully developed, and also compared
      for the electrochemical detection of DNA hybridization. The oxidation signals of
      echinomycin (ECHI) and electroactive DNA bases, guanine and adenine, respectively
      were monitored in the presence of DNA hybridization by using differential pulse
      voltammetry (DPV) technique. The biotinylated probe was immobilized onto the
      magnetic beads (magnetic particles, microspheres) and hybridization with its
      complementary target at the surface of particles within the medium was exhibited
      successfully using electrochemical sensor system. For the selectivity studies,
      the results represent that both indicator-based and indicator-free magnetic
      assays provide a better discrimination for DNA hybridization compared to duplex
      with one-base or more mismatches. The detection limits (S/N=3) of the magnetic
      assays based on indicator or indicator-free were found in nM concentration level
      of target using disposable sensor technology with good reproducibility. The
      characterization and advantages of both proposed magnetic assays connected with a
      disposable electrochemical sensor are also discussed and compared with those
      methods previously reported in the literature.

PMID- 19174224
TI  - Improvement in protein separation in Barretts esophagus samples using two
      dimensional capillary electrophoresis analysis in presence of cyclodextrins as
      buffer additives.
AB  - In two-dimensional capillary electrophoresis (2DCE) components are separated
      based on their size and hydrophobicity. A preliminary run separates analytes in
      the first capillary based on size (CSE). Following that, fractions are
      electrokinetically transferred across an interface into a second capillary, where
      components are further resolved according to hydrophobicity. In order to succeed
      in this analysis, two orthogonal methods should be selected for the different
      modes. The transfers from the first to the second capillary must be efficient in
      order to reduce tailing effects and lost of resolution. We report a new method to
      improve the resolution with our 2DCE instrumentation using CD doped buffers. When
      methyl beta cyclodextrin (mbetaCD) is added to the 2DCE interface buffer a
      stacking effect is described in the transfers from the first to the second
      dimension. In addition to that, changes in retention times are observed when
      proteins form complex with CD's helping in the separation. Protein fingerprints
      were obtained from BE homogenates using this method in presence of methyl beta
      cyclodextrin (mbetaCD). Within-day and between-day precision has been studied in
      order to establish the reproducibility of the methodology proposed.

PMID- 19174225
TI  - Ammonia gas sensor based on electrosynthesized polypyrrole films.
AB  - In this work, design and fabrication of micro-gas-sensors, polymerization and
      deposition of poly(pyrrole) thin films as sensitive layer for the micro-gas
      sensors by electrochemical processing, and characterization of the polymer films
      by FTIR, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy
      (SEM), are reported. The change in conductance of thin polymer layers is used as
      a sensor signal. The behaviours, including sensitivity, reproducibility and
      reversibility, to various ammonia gas concentrations ranging from 8 ppm to 1000
      ppm are investigated. The influence of the temperature on the electrical response
      of the sensors is also studied. The experimental results show that these ammonia
      gas sensors are efficient since they are sensitive to ammonia, reversible and
      reproducible at room temperature.

PMID- 19174226
TI  - Wall-jet conductivity detector for microchip capillary electrophoresis.
AB  - A new end-column 'hybrid' contactless conductivity detector for microchip
      capillary electrophoresis (CE) was developed. It is based on a "hybrid"
      arrangement where the receiving electrode is insulated by a thin layer of
      insulator and placed in the bulk solution of the detection reservoir of the chip,
      whereas the emitting electrode is in contact with the solution eluted from the
      channel outlet in a wall-jet arrangement. The favorable features of the new
      detector including the high sensitivity and low noise, can be attributed to both
      the direct contact of the 'emitting' electrode with the analyte solution as well
      as to the insulation of the detection electrode from the high DC currents in the
      electrophoretic circuit. Such arrangement provides a 10-fold sensitivity
      enhancement compared to currently used on-column contactless conductivity CE
      microchip detector as well as low values of noise and easy operation. The new
      design of the wall-jet conductivity detector was tested for separation of
      explosive-related methylammonium, ammonium, and sodium cations. The new detector
      design reconsiders the wall-jet arrangement for microchip conductivity detection
      in scope of improved peak symmetry, simplified study of inter-electrode distance,
      isolation of the electrodes, position of the wall-jet electrode to the separation
      channel, baseline stability and low limits of detection.

PMID- 19174227
TI  - Label-free electrochemical aptasensor for the detection of lysozyme.
AB  - This work reports the advantages of a label free electrochemical aptasensor for
      the detection of lysozyme. The biorecognition platform was obtained by the
      adsorption of the aptamer on the surface of a carbon paste electrode (CPE)
      previously blocked with mouse immunoglobulin under controlled-potential
      conditions. The recognition event was detected from the decrease in the guanine
      and adenine electro-oxidation signals produced as a consequence of the molecular
      interaction between the aptamer and lysozyme. The biosensing platform
      demonstrated to be highly selective even in the presence of large excess (9-fold)
      of bovine serum albumin, cytochrome C and myoglobin. The reproducibility for 10
      repetitive determinations of 10.0 mg L(-1) lysozyme solution was 5.1% and 6.8%
      for guanine and adenine electro-oxidation signals, respectively. The detection
      limits of the aptasensor were 36.0 nmol L(-1) (if considering guanine signal) and
      18.0 nmol L(-1) (if taking adenine oxidation current). This new sensing approach
      represents an interesting and promising alternative for the electrochemical
      quantification of lysozyme.

PMID- 19174228
TI  - Amperometric determination of choline with enzyme immobilized in a hybrid
      mesoporous membrane.
AB  - Choline sensor is successfully prepared by using immobilized enzyme, i.e.,
      choline oxidase (ChOx) within a hybrid mesoporous membrane with 12 nm pore
      diameter (F127M). The measurement was based on the detection of hydrogen
      peroxide, which is the co-product of the enzymatic choline oxidation. The
      determination range and the response time are 5.0-800 microM and approximately 2
      min, respectively. The sensor is very stable compared to the native enzyme sensor
      and 85% of the initial response was maintained even after storage for 80 days.
      These results indicate that ChOx is successfully immobilized and well stabilized,
      and at the same time, enzyme reaction proceeds efficiently. Such ability of
      hybrid mesoporous membrane F127M suggests great promise for effective
      immobilization of enzyme useful for electrochemical biosensors.

PMID- 19174229
TI  - Biomimetic sensor based on MnIIIMnII complex as manganese peroxidase mimetic for
      determination of rutin.
AB  - A novel biomimetic sensor for rutin determination based on a dinuclear complex
      [Mn(III)Mn(II)(Ldtb)(mu-OAc)(2)]BPh(4) containing an unsymmetrical dinucleating
      ligand, 2-[N,N-bis(2-pyridylmethyl)-aminomethyl]-6-[N-(3,5-di-tert-butyl-2
      oxidoben-zyl)-N-(2-pyridylamino)aminomethyl]-4-methylphenol (H(2)Ldtb), as a
      manganese peroxidase mimetic was developed. Several parameters were investigated
      to evaluate the performance of the biomimetic sensor obtained after the
      incorporation of the dinuclear complex in a carbon paste. The best performance
      was obtained in 75:15:10% (w/w/w) of the graphite powder:Nujol:Mn(III)Mn(II)
      complex, 0.1 mol L(-1) phosphate buffer solution (pH 6.0) and 4.0x10(-5) mol L(
      1) hydrogen peroxide. The response of the sensor towards rutin concentration was
      linear using square wave voltammetry in the range of 9.99x10(-7) to 6.54x10(-5)
      mol L(-1) (r=0.9998) with a detection limit of 1.75x10(-7) mol L(-1). The
      recovery study performed with pharmaceuticals ranged from 96.6% to 103.2% and the
      relative standard deviation was 1.85% for a solution containing 1.0x10(-3) mol L(
      1) rutin (n=6). The lifetime of this biomimetic sensor was 200 days (at least 750
      determinations). The results obtained for rutin in pharmaceuticals using the
      biomimetic sensor and those obtained with the official method are in agreement at
      the 95% confidence level.

PMID- 19174230
TI  - Effect of a carboxyl group on the chemiluminescent reaction of tris(2,2'
      bipyridine)ruthenium(III) with aliphatic amines.
AB  - The effect of a carboxyl group beside nitrogen of aliphatic amines on the
      tris(2,2'-bipyridine)ruthenium(III), Ru(bpy)(3)(3+), chemiluminescent reaction
      was examined. It has been shown that a carboxylate anion promotes the
      chemiluminescent reaction at a lower pH and then the aliphatic amines with this
      substituent can be sensitively detected compared with corresponding aliphatic
      amines without this substituent. Based on this finding, preliminary studies on
      simultaneous determination of 4-hydroxyproline, N-methylglycine, N-methylalanine,
      proline, and pipecolic acid in human serum have been performed using isocratic
      reversed-phase ion-pair high-performance liquid chromatography (HPLC) with
      electrogenerated Ru(bpy)(3)(3+) chemiluminescent detection. The detection limits
      (signal-to-noise ratio of 3) with the proposed method were 3.0, 12, 2.7, 4.6, and
      10nM for 4-hydroxyproline, N-methylglycine, N-methylalanine, proline, and
      pipecolic acid, respectively.

PMID- 19174231
TI  - Simultaneous determination of multibenzodiazepines by HPLC/UV: investigation of
      liquid-liquid and solid-phase extractions in human plasma.
AB  - A method for simultaneous determination of seven benzodiazepines (BZPs)
      (flunitrazepam, clonazepam, oxazepam, lorazepam, chlordiazepoxide, nordiazepam
      and diazepam using N-desalkylflurazepam as internal standard) in human plasma
      using liquid-liquid and solid-phase extractions followed by high-performance
      liquid chromatography (HPLC) is described. The analytes were separated employing
      a LC-18 DB column (250 mm x 4.6 mm, 5 microm) at 35 degrees C under isocratic
      conditions using 5mM KH(2)PO(4) buffer solution pH 6.0:methanol:diethyl ether
      (55:40:5, v/v/v) as mobile phase at a flow rate of 0.8 mL min(-1). UV detection
      was carried out at 245 nm. Employing LLE, the best conditions were achieved with
      double extraction of 0.5 mL plasma using ethyl acetate and Na(2)HPO(4) pH 9.5 for
      pH adjusting. Employing SPE, the best conditions were achieved with 0.5 mL plasma
      plus 3 mL 0.1M borate buffer pH 9.5, which were then passed through a C18
      cartridge previously conditioned, washed for 3 times with these solvents: 3 mL
      0.1M borate buffer pH 9.5, 4 mL Milli-Q water and 1 mL acetonitrile 5%, finally
      the BZPs elution was carried with diethyl ether:n-hexane:methanol (50:30:20). In
      both methods the solvent was evaporated at 40 degrees C under nitrogen flow. The
      validation parameters obtained in LLE were linearity range of 50-1200 ng mL(-1)
      plasma (r>or=0.9927), limits of quantification of 50 ng mL(-1) plasma, within-day
      and between-day CV% and E% for precision and accuracy lower than 15%, and
      recovery above 65% for all BZPs. In SPE, the parameter obtained were linearity
      range of 30-1200 ng mL(-1) plasma (r>or=0.9900), limits of quantification of 30
      ng mL(-1) plasma, within-day and between-day CV% and E% for precision and
      accuracy lower than 15% and recovery above 55% for all BZPs. These extracting
      procedures followed by HPLC analysis showed their suitable applicability in order
      to examine one or more BZPs in human plasma. Moreover, it could be suggested that
      these procedures might be employed in various analytical applications, in special
      for toxicological/forensic analysis.

PMID- 19174232
TI  - An assay for identification and determination of toxic rodenticide valone in
      serum by ion chromatography-electrospray ionization tandem mass spectrometry with
      ion trap detector.
AB  - Valone has a chronic and toxic anticoagulant rodenticide that has widely used in
      China and has resulted in some accidental and intentional intoxication in recent
      years. The literature reported so far lacks sensitive and selective method for
      the confirmation of valone. The purpose of this study was to establish a novel
      assay for the identification and quantification of valone in serum by ion
      chromatography-electrospray ionization tandem mass spectrometry (IC-MS/MS). After
      serum sample was extracted with methanol/acetonitrile (10:90, v/v) and cleaned by
      Oasis HLB solid-phase extraction cartridge, chromatographic separation was
      performed on an Ionpac AS11 column with an eluent of methanol/30 mmol/L KOH
      (10:90, v/v). The overall extraction efficiency was >81.0%, and the limit of
      quantification was 0.5 ng/mL for valone. Regression analysis of the calibration
      data revealed good correlation (r(2)>0.99) for valone. Intra- and inter-day
      precisions for quality-control samples were less than 8.0 and 13.7%,
      respectively. The proposed method enables the identification and quantification
      of valone in both clinical and forensic specimens.

PMID- 19174233
TI  - Direct electrochemistry of cytochrome c on a phosphonic acid terminated self
      assembled monolayers.
AB  - The direct electrochemistry of cytochrome c (cyt c) on a gold electrode modified
      with 3-mercaptopropylphosphonic acid [HS-(CH(2))(3)-PO(3)H(2), MPPA] self
      assembled monolayers (SAMs) was for the first time investigated. Electrochemical
      measurements and surface-enhanced infrared absorption spectroscopic reveal that
      the adsorption kinetics of cyt c on the MPPA-SAMs is very fast (saturation
      adsorption is completed within 5s) and the immobilized cyt c molecules retain
      their native secondary protein structure. The nature of interaction between cyt c
      and -PO(3)H(2) groups is mainly the electrostatic interaction. The direct
      electrochemistry of the immobilized cyt c on the -PO(3)H(2) terminated SAMs with
      short chain is nearly reversible. Its formal potential (E(0)'=18+/-3 mV vs. SCE)
      is very close to that of cyt c in an aqueous solution (E(0)'=18-22 mV vs. SCE).
      In addition, the electron transfer rate of cyt c immobilized on -PO(3)H(2)
      terminated SAMs is relatively slow as compared to -SO(3)H and -COOH terminated
      SAMs, indicating excess negative charge density on the SAMs surface will decrease
      the electron transfer rate of cyt c.

PMID- 19174234
TI  - Specific mercury(II) adsorption by thymine-based sorbent.
AB  - A new kind of polymer sorbent based on the specific interaction of Hg(II) with
      nucleic acid base, thymine, is described for the selective adsorption of Hg(II)
      from aqueous solution. Two types of sorbents immobilized with thymine were
      prepared by one-step swelling and polymerization and graft polymerization,
      respectively. The maximum static adsorption capacity of the new polymer sorbents
      for Hg(II) is proportional to the density of thymine on their surface, up to
      200mg/g. Moreover, the new kind polymer sorbent shows excellent selectivity for
      Hg(II) over other interfering ions, such as Cu(II), Cd(II), Zn(II), Co(II),
      Ca(II) and Mg(II), exhibits very fast kinetics for Hg(II) adsorption from aqueous
      solution, and can be easily regenerated by 1.0M HCl. It also has been
      successfully used for the selective adsorption of spiked Hg(II) from real tap
      water samples. This new thymine polymer sorbent holds a great promise in
      laboratory and industrial applications such as separation, on-line enrichment,
      solid-phase extraction, and removal of Hg(II) from pharmaceutical, food and
      environmental samples.

PMID- 19174235
TI  - Immunoaffinity extraction of testosterone by antibody immobilized monolithic
      capillary with on-line laser-induced fluorescence detection.
AB  - An immunoaffinity capillary column has been made with poly (2-vinyl-4, 4
      dimethylazlactone-co-2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) (VDA
      co-HEMA-co-EDMA) monolith as a support for the immobilized antibody. The monolith
      is prepared by UV-initiated in situ polymerization, followed by immobilizing anti
      testosterone polyclonal antibody through the rapid reaction with VDA.
      Fluorescence labeled testosterone at C(3) is designed as a tracer to estimate the
      extraction ability of this immunoaffinity column, and to optimize the
      immunoextraction process, such as washing, eluting, incubation and injection. The
      performance in a more realistic application is then demonstrated successfully for
      the rapid extraction of testosterone (T) by competitive immunoassay and on-line
      laser-induced fluorescence (LIF) detection. This immunoaffinity monolith is
      easily prepared, with high mechanical strength and low flow resistance. It is a
      satisfactory material as an immunoextractor to detect small molecular compounds
      specifically and rapidly with high sensitivity (sub ng/mL level).

PMID- 19174236
TI  - Sensitivity enhancement of SPR biosensor with silver mirror reaction on the Ag/Au
      film.
AB  - Based on well-known silver mirror reaction the Ag film was formed on Au film
      modified by self-assembled monolayer (SAM) of 1,6-hexanedithiol (HDT). The
      sensitivity of the biosensor based on this Ag/Au film is enhanced compared to
      that based on Au film. When the surface plasmon resonance (SPR) biosensor based
      on this Ag/Au film was used to determine human IgG, the range of concentrations
      of human IgG that could be determined is 0.30-40.00 microg mL(-1). The lowest
      concentration (0.30 microg mL(-1)) that could be detected was about 8 times lower
      than that obtained by the biosensor without modification by Ag film (2.50 microg
      mL(-1)), which demonstrated that the biosensor based on Ag/Au film could make the
      resonant wavelength move to longer wavelength following with the sensitivity
      enhancement of the SPR biosensor.

PMID- 19174237
TI  - Single-drop micro-extraction and diffuse reflectance Fourier transform infrared
      spectroscopic determination of chromium in biological fluids.
AB  - The present paper deals with a new micro-extraction procedure for selective
      separation of Cr(VI) in the form of a metaloxy anionic species namely dichromate
      (Cr(2)O(7)(2-)) with N(1)-hydroxy-N(1),N(2)-diphenylbenzamidine (HOA) in to
      dichloromethane and its subsequent and rapid diffuse reflectance Fourier
      transform infrared spectroscopic (DRS-FTIR) determination employing potassium
      bromide matrix. The diffuse reflectance Fourier transform infrared spectroscopy
      gives both qualitative and quantitative information about the dichromate. The
      determination of chromium is based on the analytical peak selection, among the
      various vibrational peaks, at 902 cm(-1). The micro-extraction was based on the
      liquid-liquid solvent extraction (LLSE) principle. The dichromate binds with the
      nitrogen and oxygen atoms of N(1)-hydroxy-N(1),N(2)-diphenylbenzamidine (HOA) and
      forms 1:2, Cr(VI):HOA complex in 0.1 mol L(-1) HCl medium. The formation of above
      complex, in the acidic medium, is confirmed by the appearance of chocolate-brown
      color in the micro-extract. The speciation studies of Cr(III) and Cr(VI) is done
      by conversion of Cr(III) into Cr(VI) utilizing H(2)O(2) as an oxidizing agent.
      The chemistry of pure dichromate and that of its HOA complex is discussed. The
      limit of detection (LoD) and the limit of quantification (LoQ) of the method are
      found to be 0.01 microg g(-1) Cr(2)O(7)(2-) and 0.05 microg g(-1) Cr(2)O(7)(2-),
      respectively. The standard deviation value and the relative standard value at a
      level of 10 microg Cr(2)O(7)(2-)/0.1g KBr for n=10 is found to be 0.26 microg
      Cr(2)O(7)(2-) and 2.6%, respectively. The relative standard deviation (n=8 and 6)
      for the determination of dichromate (Cr(2)O(7)(2-)) in real human biological
      fluid samples is observed to be in the range 3.1-7.8%.

PMID- 19174238
TI  - Computer-aided target optimization for traditional Chinese medicine by ultra
      performance liquid chromatography.
AB  - A new strategy of target optimization was developed for resolving the separation
      problems of complex samples. Computer-aided target optimization for separation of
      complex samples by ultra-performance liquid chromatography (UPLC) was studied.
      Taking traditional Chinese medicine (TCM) (Rhizoma Coptidis) as an example,
      separation conditions of target compounds - overlapping peaks and all components 
      were optimized based on moved overlapping separation ranging map (OSRM) and
      artificially intervention. After calculating retention parameters and peak shape
      parameters of the target peaks, the optimization was operated in an emulational
      picture through the computer without further experiments. The emulational
      chromatogram was proved to be authentic by the estimated values, which were
      almost identical to experimental results. The method was very helpful for
      obtaining the satisfied separation conditions of target compounds rapidly and
      efficiently.

PMID- 19174239
TI  - Highly-sensitive cholesterol biosensor based on well-crystallized flower-shaped
      ZnO nanostructures.
AB  - This paper reports the fabrication of highly-sensitive cholesterol biosensor
      based on cholesterol oxidase (ChOx) immobilization on well-crystallized flower
      shaped ZnO structures composed of perfectly hexagonal-shaped ZnO nanorods grown
      by low-temperature simple solution process. The fabricated cholesterol biosensors
      reported a very high and reproducible sensitivity of 61.7 microA microM(-1)cm(-2)
      with a response time less than 5s and detection limit (based on S/N ratio) of
      0.012 microM. The biosensor exhibited a linear dynamic range from 1.0-15.0 microM
      and correlation coefficient of R=0.9979. A lower value of apparent Michaelis
      Menten constant (K(m)(app)), of 2.57 mM, exhibited a high affinity between the
      cholesterol and ChOx immobilized on flower-shaped ZnO structures. Moreover, the
      effect of pH on ChOx activity on the ZnO modified electrode has also been studied
      in the range of 5.0-9.0 which exhibited a best enzymatic activity at the pH range
      of 6.8-7.6. To the best of our knowledge, this is the first report in which such
      a very high-sensitivity and low detection limit has been achieved for the
      cholesterol biosensor by using ZnO nanostructures modified electrodes.

PMID- 19174240
TI  - Comparison of ICP-MS and SIMS techniques for determining uranium isotope ratios
      in individual particles.
AB  - The determination of uranium isotope ratios in individual particles is of great
      importance for nuclear safeguards. In the present study, an analytical technique
      by inductively coupled plasma mass spectrometry (ICP-MS) with a desolvation
      sample introduction system was applied to isotope ratio analysis of individual
      uranium particles. In ICP-MS analysis of individual uranium particles with
      diameters ranging from 0.6 to 4.2 microm in a standard reference material (NBL
      CRM U050), the use of the desolvation system for sample introduction improved the
      precision of (234)U/(238)U and (236)U/(238)U isotope ratios. The performance of
      ICP-MS with desolvation was compared with that of a conventionally used method,
      i.e., secondary ion mass spectrometry (SIMS). The analysis of test swipe samples
      taken at nuclear facilities implied that the performance of ICP-MS with
      desolvation was superior to that of SIMS in a viewpoint of accuracy, because the
      problems of agglomeration of uranium particles and molecular ion interferences by
      other elements could be avoided. These results indicated that ICP-MS with
      desolvation has an enough ability to become an effective tool for nuclear
      safeguards.

PMID- 19174241
TI  - On-line solid phase extraction coupled to capillary LC-ESI-MS for determination
      of fluoxetine in human blood plasma.
AB  - An instrumental setup including on-line solid phased extraction coupled to
      capillary liquid chromatography-electrospray ionization-mass spectrometry (SPE
      capLC-ESI-MS) has been constructed to improve the sensitivity for quantification
      of fluoxetine hydrochloride in human plasma. Prior to injection, 0.5 mL of plasma
      spiked with metronidazole (internal standard) was mixed with ammonium formate
      buffer for effective chloroform liquid-liquid extraction. The method was
      validated in the range 5-60 ng mL(-1) fluoxetine, yielding a correlation
      coefficient of 0.999 (r(2)). The within-assay and between-assay precisions were
      between (8.5 and 11%) and (6.6 and 7.5%), respectively. The method was used to
      determine the amount of fluoxetine in a healthy male 14 h after an intake of one
      capsule of the antidepressant and anorectic Flutin, which contains 20mg
      fluoxetine per each capsule. Fluoxetine was detected, and the concentration was
      calculated to 9.0 ng mL(-1) plasma. In the preliminary experiments, conventional
      LC-UV instrumentation was employed. However, it was found that employing a
      capillary column with an inner diameter of (0.3mm I.D. x 50 mm, Zorbax C(18))
      increased the sensitivity by a factor of approximately 100, when injecting the
      same mass of analyte. Incorporating an easily automated C(18) reversed phase
      column switching system with SPE (1.0mm I.D. x 5.0mm, 5 microm) made it possible
      to inject up to 100 microL of solution, and the total analysis time was 5.5 min.

PMID- 19174242
TI  - Detection of water in jet fuel using layer-by-layer thin film coated long period
      grating sensor.
AB  - The quantitative measurement of jet fuel additives in the field is of interest to
      the Air Force. The "smart nozzle" project was designed as a state-of-the-art
      diagnostics package attached to a single-point refueling nozzle for assessing key
      fuel properties as the fuel is dispensed. The objective of the work was to show
      proof of concept that a layer-by-layer thin film and long period grating fibers
      could be used to detect the presence of water in jet fuel. The data for the
      nafion/PDMA film and a long period grating fiber is a combination capable of
      quantitative measurement of water in kerosene. The average response (spectral
      loss wavelength shift) to the kerosene sample ranged from -6.0 for 15 ppm to 
      126.5 for 60 ppm water. The average calculated value for the check standard was
      21.71 and ranged from 21.25 to 22.00 with a true value of 22.5 ppm water.
      Potential interferences were observed and are judged to be insignificant in real
      samples.

PMID- 19174243
TI  - Long-wavelength homogeneous enzyme immunoassay for the determination of amikacin
      in water samples.
AB  - A simple and rapid homogeneous enzyme immunoassay involving the use of the malic
      dehydrogenase enzyme and a long-wavelength fluorophor, the oxazine Cresyl Violet,
      is proposed for the determination of the antibiotic amikacin in water samples. An
      enzymatic tracer has been synthesized by covalent binding of amikacin to malic
      dehydrogenase via a carbodiimide derivative. Free tracer catalyses the reaction
      between Cresyl Violet and malic acid giving rise to a decrease in the
      fluorescence of the fluorophor. Kinetic curves for this reaction have been
      monitored at lambda(ex) 585 and lambda(em) 624 nm using the stopped-flow mixing
      technique, being the initial rate measured in only 2-3s. The dynamic range of the
      method is 1-15 ng mL(-1) and the detection limit is 0.3 ng mL(-1), using aqueous
      standard solutions or water samples. The precision, obtained at 1 and 5 ng mL(-1)
      and expressed as relative standard deviation, was 6.0 and 9.6%, respectively. The
      method has been applied to the analysis of drinking, river and wastewater
      samples. The sample pre-treatment involved a solid-phase extraction step for the
      clean-up of the samples. A recovery study was carried out to validate the method,
      being the values obtained in the range 80-114%, with a mean value of 96.7%.

PMID- 19174244
TI  - A direct RP-HPLC method for the determination of furanic aldehydes and acids in
      honey.
AB  - In this study 5-hydroxymethyl-2-furaldehyde (HMF), 2-furaldehyde, 3-furaldehyde,
      2-furoic acid and 3-furoic acid are contemporarily determined in honey using a
      swift and direct RP-HPLC approach. The validation protocol was performed in terms
      of detection and quantification limits, precision (by repeatability and
      reproducibility), linearity and accuracy (by recovery tests); the acceptability
      of the precision and accuracy results was positively verified using Horwitz's
      model and AOAC guidelines, respectively. The method was tested on 18 honey
      samples of different ages, and botanical and geographical origin. HMF and 2
      furaldehyde correlated highly with the age of the samples, whereas no correlation
      was observed with regards to 2-furaldehyde and 2-furoic acid. Hypotheses relating
      to the formation of minority furanic compounds are also proposed.

PMID- 19174245
TI  - Reverse flow injection analysis of nanomolar soluble reactive phosphorus in
      seawater with a long path length liquid waveguide capillary cell and
      spectrophotometric detection.
AB  - A novel reverse flow injection analysis method coupled with a liquid waveguide
      capillary cell (LWCC) and spectrophotometric detection for the determination of
      nanomolar soluble reactive phosphorus in seawater was established. Reagent was
      injected into the sample stream and detected in a 2-m path length LWCC with
      detection wavelength set at 710 nm. Experimental parameters, including the
      reagent concentration, the injection volume, the flow rate and the length of the
      mixing coil, were optimized based on univariate experimental design. The
      interference of silicate and arsenate were also investigated. Under optimized
      conditions, the linearity and the detection limit of the proposed method were
      found to be 0-165.0 nM and 0.5 nM, which was estimated to be three times the
      standard deviation of the measurement blanks (n=9). The relative standard
      deviations for the determination of 24.7 and 82.5 nM samples were 1.54% and 1.86%
      (n=9), respectively. Three seawater samples were analyzed with recoveries ranging
      from 87.8% to 101.8%. Using the Student's t-test at the 95% confidence level, the
      results of the proposed method and a segmented flow analyzer reference method for
      determination of the two samples showed no significant difference. The proposed
      method had the advantages of being less reagent consuming, more sensitive and
      with higher throughput (15 h(-1)).

PMID- 19174246
TI  - Direct determination of arsine in gases by inductively coupled plasma-dynamic
      reaction cell-mass spectrometry.
AB  - Reliable determination of arsine (AsH(3)) in gases is of great importance due to
      stringent regulations associated with health, safety and environmental issues. It
      is, however, challenging for an analyst to determine trace airborne arsine
      concentrations without specifically designed collection procedures using
      adsorption, desorption, dissolution or impinging techniques. To circumvent such
      technical barrier, we have newly developed a direct analytical method,
      characterized by introduction of an arsine gas sample into stable plasma stream,
      followed by gas-phase oxidation of arsine with molecular oxygen in a dynamic
      reaction cell (DRC) equipped within the inductively coupled plasma-mass
      spectrometry (ICP/MS) system, followed by subsequent detection of AsO(+) ion.
      This preliminary work used trace arsine concentrations (161 microg m(-3), 322
      microg m(-3), and 645 microg m(-3)) gravimetrically prepared in N(2) balance. The
      proposed method was optimized for the important experimental parameters such as
      the flow rates of the reaction gas, the arsine sample, and the carrier gas. This
      method was then validated by demonstrating good figure-of-merits including the
      low limit of detection (0.10 microg m(-3)), good linearity (r(2)>0.9915), low
      measurement uncertainty (0.66%), and high speed of analysis (<6 min). The
      proposed method is expected to be potentially applicable to the determination of
      arsine in real workplace air after appropriate modifications are made.

PMID- 19174247
TI  - A tribute to: Jack L. Cronenwett, MD, editor-in-chief James M. Seeger, MD, Senior
      Editor the Journal of Vascular Surgery January 1, 2003-December 31, 2008.

PMID- 19174248
TI  - A message from the new editors.

PMID- 19174249
TI  - Supra-aortic vessels aneurysms: diagnosis and prompt intervention.
AB  - PURPOSE: Aneurysms involving the supra-aortic vessels are rare but carry serious
      risk of embolization, thrombosis, and rupture. We describe our experience with
      the diagnosis, treatment strategies, and outcomes in patients with extended
      follow-up. METHODS: Data during a 17-year period (January 1990 to December 2007)
      was analyzed. We assessed age, gender, presenting symptoms, localization,
      pathologic diagnosis, type of procedures, complications, and survival. RESULTS: A
      total of 74 patients were treated for supra-aortic aneurysms. Of all aneurysms
      treated, 63% were degenerative, 24% iatrogenic, 8% traumatic, 3% genetic, and 1%
      mycotic. The subclavian artery was most commonly affected (50%, 2/3 in the right
      side), followed by the common carotid (36%), internal carotid (10%), innominate
      (3%), and vertebral (1%). At the time of diagnosis, 52 patients (70%) were
      asymptomatic, but of those symptomatic 68% had an embolic event as a presenting
      symptom. Embolic episodes were more common in patients with smaller aneurysms (P
      < .006). Open surgery was performed in 77% of all cases, and the use of
      endovascular techniques became the predominant treatment modality over the last 4
      years. Survival at 30 days was 100%. Five- and 10-year survival rates were 87%
      and 43%, respectively. CONCLUSION: Most cases of supra-aortic aneurysm are
      asymptomatic and embolization as opposed to rupture represents the greatest risk
      to the patient. Most cases can be detected prior to symptoms. Endovascular repair
      is an emerging alternative of treatment and, with the current development of
      appropriate devices, will likely form the mainstay of therapy in the near future.

PMID- 19174250
TI  - Comparison of EVAR and open repair in patients with small abdominal aortic
      aneurysms: can we predict results of the PIVOTAL trial?
AB  - OBJECTIVE: Data from multicenter studies support observation of small abdominal
      aortic aneurysms (AAAs) over open repair (OR), but the role of endovascular
      repair (EVAR) is unclear pending outcome of the Positive Impact of EndoVascular
      Options for Treating Aneurysm earLy (PIVOTAL) trial. Our goal was to predict the
      outcome of the trial by comparing results of small AAA repair using EVAR vs OR at
      a tertiary institution. METHODS: Using selection criteria of PIVOTAL trial, we
      reviewed clinical data of 194 consecutive patients, who underwent EVAR or OR for
      4.0-5.0 cm AAAs between 1997 and 2004. All-cause and aneurysm-related deaths,
      complications, reinterventions, ruptures, and conversions were documented;
      factors affecting outcome were analyzed using chi(2) tests, Wilcoxon rank-sum
      tests, logistic regression Kaplan-Meier method with log-rank tests, and Cox
      proportional hazards regression. Median follow-up was 3.9 years (range, 1 month
      to 9 years). RESULTS: A total of 194 patients, 162 males, 32 females (mean age:
      71 years, range, 46-86) underwent 162 OR and 32 EVAR. EVAR patients were older
      (mean 74 +/- 6 vs 71 +/- 7, P = .002), had lower ejection fraction (mean 54 +/-
      11 vs 61 +/- 13, P = .0002), and less likely to have ever smoked (69% vs 85%, P =
      .03) than OR patients. Thirty-day mortality was 1.3% (2/162) for OR and 0% for
      EVAR (0/33) (P = not significant [NS]). There were 49 systemic complications (7
      EVAR, 42 OR, P = NS) and 10 local complications (3 EVAR, 7 OR, P = NS). During
      follow-up, there were no conversions and no ruptures. Freedom from
      reinterventions at 5 years was 83.1% +/- 6.9% for EVAR and 95.3% +/- 1.8% for OR
      (P = 0.02). There were 26 deaths (3 EVAR, 23 OR); but no procedure or aneurysm
      related death was confirmed after 30 days (cause unknown in 16 deaths, 62%).
      Survival rates at 1-year were 96.6% +/- 3.4% for EVAR and 97.4% +/- 1.3% for OR;
      5-year rates were 86.9% +/- 7.2% +/- EVAR and 86.9% +/- 3.3% for OR (P = 0.69).
      Multivariate analysis revealed age (hazard ratio = 1.1 per year, P = .0496) and
      AAA size (hazard ratio = 13.8 per 1 cm, P = .03) were associated with death but
      EVAR vs OR was not (P = .23). CONCLUSION: For repair of small AAAs, results of
      EVAR vs OR are not different at 5 years at a tertiary institution. Multicenter
      studies confirmed OR were not superior to observation in these patients. We
      predict the PIVOTAL study will conclude EVAR is not superior to observation.

PMID- 19174252
TI  - Duplex criteria for determination of in-stent stenosis after angioplasty and
      stenting of the superficial femoral artery.
AB  - OBJECTIVE: Endovascular intervention is considered first-line therapy for most
      superficial femoral artery (SFA) occlusive disease. Duplex ultrasound (DU)
      criteria for SFA in-stent stenosis and correlation with angiographic data remain
      poorly defined. This study evaluated SFA-specific DU criteria for the assessment
      of SFA in-stent stenosis. METHODS: From May 2003 to May 2008, 330 limbs underwent
      SFA angioplasty and stenting and were monitored by serial DU imaging. Suspected
      stenotic lesions underwent angiography and intervention when appropriate. Data
      pairs of DU and angiographically estimated stenosis <or=30 days of each other
      were analyzed. Seventy-eight limbs met these criteria, and 59 underwent
      reintervention. In-stent peak systolic velocity (PSV), the ratio of the stented
      SFA velocity/proximal SFA velocity, changes in ankle-brachial indices (ABIs), and
      the percentage of angiographic stenosis were examined. Linear regression and
      receiver operator characteristic (ROC) curve analyses were used to compare
      angiographic stenosis with PSV and velocity ratios (Vrs) to establish optimal
      criteria for determining significant in-stent stenosis. RESULTS: Mean follow-up
      was 16.9 +/- 8.3 months. Of the 59 limbs that underwent reintervention, 37 (63%)
      were symptomatic, and 22 (37%) underwent reintervention based on DU findings
      alone. Linear regression models of PSV and Vr vs degree of angiographic stenosis
      showed strong adjusted correlation coefficients (R(2) = 0.60, P < .001 and R(2) =
      0.55, P < 0.001, respectively). ROC curve analysis showed that to detect a
      >or=50% in-stent stenosis, a PSV >or=190 had 88% sensitivity, 95% specificity, a
      98% positive predictive value (PPV), and a 72% negative predictive value (NPV);
      for Vr, a ratio of >1.50 had 93% sensitivity, 89% specificity, a 96% PPV, and a
      81% NPV. To detect >or=80% in-stent stenosis, a PSV >or=275 had 97% sensitivity,
      68% specificity, a 67% PPV, and a 97% NPV; a Vr ratio >or=3.50 had 74%
      sensitivity, 94% specificity, a 77% PPV, and a 88% NPV. Combining a PSV >or=275
      and a Vr >or=3.50 to determine >or=80% in-stent stenosis had 74% sensitivity, 94%
      specificity, a 88% PPV, and a 85% NPV; odds ratio was 42.17 (95% confidence
      interval, 10.20-174.36, P < .001) to predict >or=80% in-stent stenosis. A
      significant drop in ABI (>0.15) correlated with a >62% in-stent stenosis,
      although the adjusted correlation coefficients was low (R(2) = 0.31, P = .02).
      CONCLUSION: PSV and Vr appear to have a significant role in predicting in-stent
      stenosis. To determine >or=80% stenosis, combining PSV >or=275 cm/s and Vr
      >or=3.50 is highly specific and predictive.

PMID- 19174255
TI  - Staged endovascular treatment of bilateral ruptured and intact ovarian artery
      aneurysms in a postmenopausal woman.
AB  - Ovarian artery aneurysms have rarely been reported in the literature, with almost
      all being unilateral and occurring in the peripartum period. We herein describe a
      unique case of a postmenopausal patient with a ruptured ovarian aneurysm and an
      intact contralateral aneurysm that were both successfully treated by endovascular
      techniques.

PMID- 19174256
TI  - Recurrent refractory arterial thromboembolism associated with the Janus kinase 2
      V617F mutation.
AB  - We report two patients with peripheral vascular disease requiring multiple
      bilateral radiologic and surgical interventions, and whose disease was
      unresponsive to conventional anticoagulation and antiplatelet therapy. Although
      thrombocytosis was only intermittent, analysis of the Janus kinase 2 (JAK2) gene
      revealed a V617F mutation, thus confirming the presence of an underlying occult
      myeloproliferative disorder. We propose that JAK2 mutation analysis be considered
      in patients with recurrent, unexplained arterial events to identify those with
      occult myeloproliferative disorders.

PMID- 19174257
TI  - Renal artery pseudoaneurysm caused by a complete stent fracture: a case report.
AB  - We report the case of a 71-year-old man with acute back and left flank pain
      caused by a large pseudoaneurysm of the left renal artery. The pseudoaneurysm
      resulted from a complete fracture of a stent that had been placed at the origin
      of this vessel 10 months earlier. Because the left kidney had no residual
      function, the patient was treated by percutaneous occlusion of the left renal
      artery with a vascular plug. The symptoms rapidly subsided, and he remained
      symptom free at the 6-month follow-up. Stent fractures, their complications, and
      management are discussed.

PMID- 19174258
TI  - Peripheral artery leiomyosarcoma.
AB  - Vascular leiomyosarcomas are extremely rare tumors and represent only 0.001% of
      all malignancies. Venous leiomyosarcomas occur five times more often than
      arterial ones, with 50% of them originating in the inferior vena cava (IVC).
      Arterial leiomyosarcomas are most commonly encountered in the great vessels with
      less than 50% of them occurring in the peripheral circulation. A total of only
      seven cases of arterial leiomyosarcomas involving the femoral artery have been
      reported in literature to date. We report a case of an arterial leiomyosarcoma
      involving the profunda femoris artery, and provide a comprehensive review on
      peripheral arterial leiomyosarcomas-distribution, clinical presentation,
      radiological and histological diagnosis, staging, and treatment.

PMID- 19174259
TI  - Compression therapy and liposuction of lower legs for bilateral hereditary
      primary lymphedema praecox.
AB  - In this report, we describe a case of bilateral non-syndromic hereditary
      lymphedema praecox of lower legs. The patient was diagnosed at age 16. Ten years
      later, he was unable to ambulate due to increased bilateral lower leg volume,
      continuous pain, and recurrent episodes of cellulitis. He was treated at our
      tertiary-care center with compression therapy and circumferential liposuction of
      lower legs, ankles, and dorsum of feet in order to remove hypertrophic fat
      deposits, facilitate conservative therapy, and decrease further risk of
      cellulitis. No complications were seen and compression therapy was continued.
      Fourteen month follow-up reveals no increase in leg volume over time, absence of
      pain, and no further episodes of cellulitis with complete ability to ambulate and
      return to normal activities. Even when it does not eliminate the underlying cause
      of primary lymphedema, combined therapy consisting of compression and liposuction
      is safe and is able to achieve control, at least on a short term, of clinically
      disabling conditions associated with advanced stages.

PMID- 19174260
TI  - Iliac side branch device for bilateral endovascular exclusion of isolated common
      iliac artery aneurysms without brachial access.

PMID- 19174261
TI  - The role of SVS volunteer vascular surgeons in the care of combat casualties:
      results from Landstuhl, Germany.
AB  - With a shortage of active duty vascular surgeons in the military, Society for
      Vascular Surgery (SVS) members have been called upon to perform short-term
      rotations at Landstuhl Regional Medical Center (LRMC), the US military's
      receiving facility for combat injuries sustained in the Iraq and Afghanistan
      conflicts. From September 2007 to May 2008, 20 SVS vascular surgeons have
      performed 2-week rotations at LRMC through American Red Cross and US Army
      sponsorship. Volunteers were surveyed for previous military and/or trauma
      experience. In addition to reporting number and types of procedures performed,
      volunteers were queried on their experience and impression of the rotation.
      Several volunteers have had prior military experience and all have had vascular
      trauma experience through residency, fellowship, and current practices. With most
      definitive vascular repairs being done in theater, SVS members were most often
      called upon for clinical expertise in the care of combat casualties and
      evaluation of revascularization procedures. The volunteers contributed to daily
      rounds, patient care, and teaching conferences, as well as actively participated
      in surgical procedures with the most common being wound examinations under
      anesthesia for which intraoperative vascular consultation was occasionally
      requested (5-20 per volunteer). Additional procedures that volunteers performed
      included: inferior vena cava (IVC) filter placement, thrombectomy, revision of
      lower and upper extremity interposition vein grafts, retroperitoneal spine
      exposures, diagnostic and therapeutic angiograms, iliac stenting, and duplex
      ultrasound scan interrogation of vascular repairs, suspected arterial injuries,
      and deep vein thrombosis. All volunteers described the experience as valuable and
      will return if needed. With a limited number of military vascular surgeons and
      the unpredictable need for a vascular specialist at LRMC, civilian volunteers are
      playing an important role in providing high-quality vascular care for the
      nation's wounded soldiers by expanding vascular and endovascular capability at
      LRMC and contributing to general surgical critical care. As volunteers, SVS
      members are carrying on a tradition started by our surgical forefathers during
      previous US military conflicts.

PMID- 19174262
TI  - Dominions of surrogate opinions: who is in charge?

PMID- 19174263
TI  - Technique for subclavian to carotid transposition, tips, and tricks.
AB  - When performed properly, a transposition is the most efficient and most durable
      procedure for reconstructing the subclavian artery for proximal occlusive disease
      or to extend the landing zone in the aortic arch prior to endovascular therapy
      for thoracic aortic pathology. The proximal subclavian artery, on the right or on
      the left, is approached quite differently than it is for a bypass procedure. The
      technique is described in detail here. There are very few contraindications to
      transposition, the advantages over the alternate options are many, and it can be
      the approach of choice in the vast majority of patients.

PMID- 19174264
TI  - A cylindrical femoral vein panel graft for caval reconstructions.
AB  - This report describes a simple venous reconstructive technique that results in an
      autogenous vascular graft with sufficient luminal diameter for replacing the vena
      cava. The majority of vena caval reconstructions are performed using prosthetic
      grafts; however, graft infection is a concern in clean-contaminated hepatobiliary
      and retroperitoneal resections.

PMID- 19174265
TI  - The benefit of statins in non-cardiac vascular surgery patients.
AB  - There is overwhelming evidence that statins reduce morbidity and mortality in
      patients with coronary disease. Statins have also been shown to reduce the risk
      of (recurrent) stroke. Low-density lipoprotein (LDL)-cholesterol, which plays a
      causal role in the development of atherosclerotic disease, is the primary lipid
      target in prevention, and is effectively reduced by these agents. In this review,
      studies are summarized addressing the issues whether statins also directly
      influence the atherosclerotic process in peripheral arterial disease, carotid
      artery stenosis, and growth of abdominal aortic aneurysms, and whether statins
      have an effect on perioperative outcomes in vascular surgery patients. It appears
      that the evidence of statins on peripheral arterial disease is scarce and its
      effect on perioperative outcome inconclusive. Prospective randomized trials to
      answer these questions cannot be performed anymore, however, because all vascular
      patients should receive statin treatment as secondary prevention of
      cardiovascular disease.

PMID- 19174266
TI  - The PIVOTAL study: a randomized comparison of endovascular repair versus
      surveillance in patients with smaller abdominal aortic aneurysms.
AB  - The diameter of an abdominal aortic aneurysm (AAA) is the single most important
      factor in deciding whether to repair an aneurysm or to monitor it conservatively.
      Open surgical repair does not appear to be beneficial until the diameter of the
      aneurysm is >5.5 cm. Prospective clinical trials, however, confirmed a lower risk
      of operative mortality after endovascular aneurysm repair (EVAR) than after open
      surgical repair. Further, retrospective analyses of EVAR databases suggested that
      EVAR outcome is directly related to aneurysm size and is better for smaller
      aneurysms than for larger aneurysms. Noting similar results with open surgical
      management vs surveillance in patients with smaller AAA, lower morbidity rates
      with EVAR vs open repair, and the favorable results with EVAR in smaller
      aneurysms, a clinical trial testing the hypothesis that EVAR is beneficial in
      patients with small AAA appeared warranted. To answer this question, the 70-site
      Positive Impact of endoVascular Options for Treating Aneurysm earLy (PIVOTAL) was
      begun. PIVOTAL has an enrollment goal of up to 1025 patients with a 4- to 5-cm
      AAA, randomly assigning patients to EVAR or surveillance. The primary end points
      of PIVOTAL are aneurysm rupture and AAA-related death at up to 36 months after
      randomization. When complete, the results of PIVOTAL should provide objective
      evidence to guide the use of EVAR for small AAAs.

PMID- 19174269
TI  - Regarding "Cost-effectiveness analysis of elective endovascular repair compared
      with open surgical repair of abdominal aortic aneurysms for patients at a high
      surgical risk: a 1-year patient-level analysis conducted in Ontario, Canada".

PMID- 19174272
TI  - Regarding "Symptomatic acute occlusion of the internal carotid artery:
      reappraisal of urgent vascular reconstruction based on current stroke imaging".

PMID- 19174273
TI  - Regarding "Reference value of transcutaneous oxygen measurement in diabetic
      patients compared with nondiabetic patients".

PMID- 19174274
TI  - Regarding "Long-term results of stent graft treatment of subclavian artery
      injuries: management of choice for stable patients?".

PMID- 19174277
TI  - Regarding "Functional outcome after thoracoabdominal aneurysm repair".

PMID- 19174279
TI  - Bovine neonatology. Preface.

PMID- 19174280
TI  - Resuscitation and critical care of neonatal calves.
AB  - Neonatal morbidity and mortality are major economic concerns in both beef and
      dairy cattle in the United States. In both beef and dairy most calf death occurs
      in the early neonatal period, particularly in calves born following dystocia.
      This article focuses on the resuscitation of calves after delivery and highlights
      some therapeutic points for the care of critical calves.

PMID- 19174281
TI  - Pathophysiology of diarrhea in calves.
AB  - Infectious diarrhea in calves is most commonly associated with enterotoxigenic
      Escherichia coli, Cryptosporidium parvum, rotavirus, coronavirus, or some
      combination of these pathogens. Each of these agents leads to diarrhea through
      either secretion or malabsorption/maldigestion, though the specific mechanisms
      and pathways may differ. Specific pharmacologic control and treatment are
      dependent on gaining a greater understanding of the pathophysiology of these
      organisms.

PMID- 19174282
TI  - Salmonella in calves.
AB  - Salmonellae are endemic on most large intensive farms and salmonellosis is a
      common cause of neonatal morbidity and mortality. Disease and mortality usually
      reflect a variety of management events and environmental stressors that
      contribute to compromised host immunity and increased pathogen exposure. The
      diversity of salmonella serovars present on farms, and the potential for
      different serovars to possess different virulence factors, require the
      implementation of broad prophylactic strategies that are efficacious for all
      salmonellae. This article discusses strategies to promote host immunity and
      minimize pathogen exposure at the farm level. The benefits of control include a
      reduction in disease incidence and mortality, reduced drug and labor costs, and
      improved growth rates.

PMID- 19174283
TI  - Treatment of calf diarrhea: oral fluid therapy.
AB  - Diarrhea remains the leading cause of mortality in beef and dairy calves. Calves
      that have diarrhea frequently develop dehydration, strong ion acidosis, and
      electrolyte abnormalities, and are in a state of negative energy balance. Oral
      electrolyte therapy is a simple and economical method of addressing all of these
      potential complications. This article gives an overview of oral electrolyte
      therapy of calves, including indications, guidelines for administration, and how
      to choose an electrolyte product.

PMID- 19174284
TI  - Treatment of calf diarrhea: intravenous fluid therapy.
AB  - Severely dehydrated calves that are unable to suckle need intravenous fluids for
      effective resuscitation. Intravenous fluid therapy is also indicated for sick
      calves without obvious dehydration, such as calves with strong ion acidosis,
      ruminal acidosis (rumen drinkers), severe pneumonia, septicemia, or hypothermia.
      This article presents an updated overview of intravenous fluid therapy for
      calves, recent insights into the development of metabolic acidosis in young
      calves resulting from accumulation of D-lactate, a simplified algorithm for
      intravenous fluid therapy, and a procedure for ear vein catheterization under
      field conditions.

PMID- 19174285
TI  - Treatment of calf diarrhea: antimicrobial and ancillary treatments.
AB  - Adjunct treatment of diarrhea should be routinely undertaken in all calves with
      systemic signs of illness, manifest as fever, inappetance, or lethargy. Ancillary
      treatments with documented efficacy in undifferentiated calf diarrhea include
      parenteral administration of antimicrobials with a predominantly gram negative
      spectrum of activity, parenteral administration of non-steroidal anti
      inflammatory agents such as meloxicam and flunixin meglumine, and continued
      feeding of cow's milk. Halofuginone and azithromycin have efficacy in calves with
      diarrhea due to Cryptosporidium parvum, and their administration should be
      considered in calves documented or suspected to have cryptosporidiosis.

PMID- 19174286
TI  - Respiratory disease of the bovine neonate.
AB  - Respiratory disease is an important problem in bovine neonates. Early detection
      of clinical disease is challenging. In the newborn calf, mucous membrane color,
      character and frequency of the respiratory effort, thoracic auscultation, and
      ability to oxygenate are critical elements of the examination to determine
      whether or not respiratory disease is present. Within a few days of birth,
      screening calves for fever, abnormal nasal or ocular discharge, or an inducible
      cough finds many calves with early respiratory disease. This article describes
      respiratory conditions in newborn calves that veterinarians are most likely to
      encounter, along with diagnostic and treatment options that can be applied to
      both herd investigations and individual animals.

PMID- 19174287
TI  - Mycoplasma bovis Infections in young calves.
AB  - Mycoplasma bovis has emerged as an important pathogen of young intensively reared
      calves in North America. A variety of clinical diseases are associated with M
      bovis infections of calves, including respiratory disease, otitis media,
      arthritis, and some less common presentations. Clinical disease associated with M
      bovis often is chronic, debilitating, and poorly responsive to antimicrobial
      therapy. Current control measures are centered on reducing exposure to M bovis
      through contaminated milk or other sources, and nonspecific control measures to
      maximize respiratory defenses of the calf. This article focuses on the clinical
      and epidemiologic aspects of M bovis infections in young calves.

PMID- 19174288
TI  - Respiratory distress syndrome in calves.
AB  - Respiratory disease syndrome (RDS) is a condition of neonatal calves in which
      insufficient oxygen uptake and increased retention of carbon dioxide result in
      respiratory acidosis. This condition is more common in premature calves and seems
      to be associated with a deficiency of surfactant. Although there is no uniform
      definition of RDS, clinical signs appear as tachypnea and expiration accentuated
      by an abdominal lift and expiratory grunt, and they occur in association with
      characteristic blood gas changes. This article discusses the pathophysiology of
      RDS in calves, along with the clinical findings, diagnosis, and treatment
      options.

PMID- 19174289
TI  - Septicemia and meningitis in the newborn calf.
AB  - Neonatal infections and sepsis occur most frequently in calves with failure of
      passive transfer. If the invading bacteria are not rapidly controlled, they can
      set up focal infections, such as in growth plates, joints, or meninges, or
      generalized sepsis may occur. If not successfully treated, sepsis can lead to a
      systemic inflammatory response, multiple organ dysfunction syndromes, septic
      shock, and death. Treatments are based on selecting an appropriate antimicrobial
      drug and dosage, supportive therapy, fluid therapy, nonsteroidal anti
      inflammatory drugs, and plasma transfusion. Preventing the failure of passive
      transfer through good colostrum management is essential.

PMID- 19174290
TI  - Abomasal ulceration and tympany of calves.
AB  - This article reviews the current knowledge on the pathophysiology of abomasal
      ulcer formation and abomasal tympany in calves. The development of ulcers and
      bloat has been attributed to many factors, including coarse feed, environmental
      stress, vitamin and mineral deficiencies, and bacterial infections. This article
      discusses various factors thought to play a role in the development of these
      abomasal conditions in calves.

PMID- 19174291
TI  - Neonatal immunology.
AB  - The field of neonatal immunology and calf vaccination is going through a
      revolution in veterinary medicine. The purpose of this article is to give an
      overview of basic neonatal immunology and principles of vaccination as they
      relate to beef and dairy calves. Opinions on when and what to vaccinate calves
      for vary widely among experts; therefore, this article focuses primarily on the
      documented literature. It is likely that vaccination approaches that might be
      effective or economic for one herd may not work for another.

PMID- 19174292
TI  - Grass roots growing into travel medicine.

PMID- 19174293
TI  - Mefloquine neurotoxicity: a literature review.
AB  - A literature review revealed that mefloquine neurotoxicity has been demonstrated
      at both the preclinical and clinical levels, with nausea, dizziness, sleep
      disturbances, anxiety and psychosis, amongst other adverse neuropsychiatric
      events, reported in users. Females and individuals of low body mass index (BMI)
      are at apparent greater risk. Mechanisms of possible neurotoxicity may include
      binding to neuroreceptors and cholinesterases, inhibition of sarcoendoplasmic
      reticulum ATPase (SERCA) and interference with cellular Ca(2+) homeostasis,
      accumulation in the CNS, and reductions in CNS efflux in individuals possessing
      certain MDR1 polymorphisms. It may be prudent to avoid mefloquine in females and
      low BMI individuals, and in combination with other potentially neurotoxic agents
      such as the artemisinin antimalarials.

PMID- 19174294
TI  - Water disinfection in the mountains - state of the art recommendation paper of
      the Union Internationale des Associations d'Alpinisme Medical Commission.
AB  - This paper provides the official recommendation of the Union Internationale des
      Associations d'Alpinisme (UIAA) Medical Commission to manage the problem of safe
      drinking water. The recommendation was accepted and authorized for publication by
      the Medical Commission during their annual meeting at Treplice, Tzechia, 2008.
      Safe water is essential for mountaineers worldwide in order to balance challenges
      associated with high altitude dehydration. The paper summarizes the advantages
      and disadvantages of several procedures used to procure safe drinking water in
      the mountains or at high altitude. Limitations or critical details, which may
      cause failure of the methods are mentioned systematically. We differentiate
      between "conventional" methods, which should be preferred because they produce
      safe water and "improvisation". The latter does not produce safe water but may be
      used if conventional methods are not available for any reason. They decrease the
      concentration of pathogenic microorganisms and by this they reduce the risk of
      enteral infection. Water filtration using a ceramic filter system or chemical
      disinfection is recommended as a standard method. Boiling water should be avoided
      because it is too fuel consuming and has the potential to increase deforestation.
      Generally, with regard to infections by water or food, all mountaineers should be
      vaccinated against hepatitis A and poliomyelitis in regions where they may be at
      risk.

PMID- 19174295
TI  - Medical education, global health and travel medicine: a modern student's
      experience.
AB  - Today's medical student will practice medicine in a globalised world, where an
      understanding of travel medicine and global health will be vital. Students at UK
      medical schools are keen to learn more about these areas and yet receive little
      specific training. Tomorrow's doctors should be taught about global health and
      travel medicine if they are to be prepared to work in tomorrow's world.

PMID- 19174296
TI  - Saving tourists: the status of emergency medical services in California's
      National Parks.
AB  - BACKGROUND: Providing emergency medical services (EMS) in popular tourist
      destinations such as National Parks requires an understanding of the availability
      and demand for EMS. This study examines the EMS workload, EMS transportation
      methods, EMS funding, and EMS provider status in California's National Park
      Service units. METHODS: A retrospective review of data from the 2005 Annual
      Emergency Medical Services Report for National Park Service (NPS) units in
      California. RESULTS: Sixteen NPS units in California reported EMS activity. EMS
      program funding and training costs totaled USD $1,071,022. During 2005 there were
      84 reported fatalities, 910 trauma incidents, 663 non-cardiac medicals, 129
      cardiac incidents, and 447 first aid incidents. Sequoia and Kings Canyon National
      Parks, Yosemite National Park, Golden Gate National Recreation Area, and Death
      Valley National Park accounted for 83% of the total EMS case workload. Ground
      transports accounted for 85% of all EMS transports and Emergency Medical
      Technicians with EMT-basic (EMT-B) training made up 76% of the total 373 EMS
      providers. CONCLUSIONS: Providing EMS for tourists can be a challenging task. As
      tourist endeavors increase globally and move into more remote environments, the
      level of EMS operations in California's NPS units can serve as a model for
      developing EMS operations serving tourist populations.

PMID- 19174297
TI  - Self-reported health problems among travelers visiting Cuzco: a Peruvian Airport
      survey.
AB  - Travel related illnesses are a concern among travelers visiting developing
      countries. These illnesses affect the travelers' plans and the local tourism
      industry. Few data on travel related illnesses are available from tourist
      destinations. Foreign travelers answered a self-administered questionnaire on
      health issues at the departures area of Cuzcos' International Airport between
      August and November 2002. Self-reported travel related illnesses that occurred
      during the travelers stay in Cuzco were compared with demographic and risk
      factors. The total number of participants was 5988. Their mean age was 35.4 years
      (SD 11.4), and slightly over half were female. The most common countries of
      residence were the United States (23.5%) and the United Kingdom (20%). The median
      length of stay in Cuzco was 5 days (IQR: 4-7 days). Pre-travel advice was
      received by 93.6% of the participants. Half (47.6%) of the participants became
      ill while in Cuzco. The most common illnesses reported were diarrhea (49.8%),
      altitude sickness (43.2%), and upper respiratory infections (21.7%). Most
      participants who reported an illness treated themselves (75.5%), and only 22.1%
      sought medical attention. It is concluded that a significant burden of disease is
      observed in travelers to Cuzco. Self-medication is very common and apparently
      preferred over formal medical attention.

PMID- 19174299
TI  - Importation of visceral leishmaniasis in returning Romanian workers from Spain.
AB  - BACKGROUND: Over the past two decades visceral leishmaniasis cases and foci have
      increased in Romania, where the disease has also become a medical concern. The
      following study aimed to provide essential knowledge on early diagnosis and
      management of visceral leishmaniasis cases in Romania acquired especially by
      traveling and working in the Mediterranean countries. METHOD: Retrospective
      analysis of the medical records of the patients diagnosed with imported visceral
      leishmaniasis in a western Romanian county. RESULTS: Three patients with visceral
      leishmaniasis imported from Spain were admitted to hospital in Timisoara in 2005.
      Detailed case histories along with clinical and laboratory features are
      presented. In all the patients the final laboratory confirmation of the disease
      was by Giemsa-stained blood smears obtained by bone marrow biopsy. CONCLUSIONS:
      Since 2004, many Romanian citizens left their homeland looking for a better job
      in the Mediterranean region. Unaware of the risks of outdoor labor in warm
      climatic conditions, they accepted to live and work in improper sanitary
      conditions. Late identification of the disease resulted mainly from failure of
      the physicians to diagnose and associate the syndrome with travel.

PMID- 19174298
TI  - Study of methicillin-resistant Staphylococcus aureus on the U.S./Mexico border.
AB  - BACKGROUND: El Paso, Texas and Ciudad Juarez, Mexico comprise the largest
      U.S./Mexico border population. METHODS: Bacterial samples were collected from two
      hospitals in El Paso and two in Ciudad Juarez and transported to a reference
      microbiology laboratory in El Paso for microbial identification and antimicrobial
      susceptibility testing according to NCCLS standards. The presence of the MecA
      gene, and the prevalence of both the SSCmec IV element and the Panton-Valentine
      leukocidin were investigated by PCR in all MRSA isolates. RESULTS: A total of 201
      isolates in El Paso and 128 in Ciudad Juarez of Staphylococcus aureus were
      identified, of those, MRSA were significantly more prevalent in El Paso than in
      Ciudad Juarez [89 (44.3%) versus 10 (7.8%) respectively (p<0.0001)]. Thirty one
      (35%) of MRSA strains isolated in El Paso were community associated. CONCLUSION:
      Significantly higher prevalence of MRSA infections was documented in El Paso
      compared to Ciudad Juarez.

PMID- 19174300
TI  - An outbreak of peritonitis caused by multidrug-resistant Salmonella Typhi in
      Kinshasa, Democratic Republic of Congo.
AB  - Between October 2004 and January 2005, 144 patients with peritonitis were
      admitted to the surgical wards of Kinshasa General Hospital and a few private
      city clinics. 63 patients (44%) underwent surgical intervention because of
      intestinal perforation consistent with typhoid fever; the case fatality rate was
      53%. The majority of patients had received a course of first-line antibiotics
      such as chloramphenicol, ampicillin or co-trimoxazole before admission. On
      bacteriological investigation, Salmonella Typhi was isolated from the blood of 11
      patients with peritonitis. The isolates were all resistant to ampicillin,
      chloramphenicol, tetracycline and co-trimoxazole, but sensitive to third
      generation cephalosporins, quinolone (nalidixic acid, ciprofloxacine) and
      amoxicillin-clavulanic acid. Several factors contributed to the poor outcome of
      this disease including a) the use of inappropriate antibiotics, b) long delay in
      diagnosis, c) difficult access to health facilities. This is the first documented
      outbreak of typhoid fever caused by a multidrug-resistant S. Typhi in Kinshasa.

PMID- 19174301
TI  - Imported cases of malaria admitted to two hospitals of Margarita Island,
      Venezuela, 1998-2005.
AB  - BACKGROUND: Imported cases of malaria constitute an important public health
      problem in many countries, even in those with autochthonous cases, where disease
      could be acquired in these areas and then seen in non-endemic regions. Non-immune
      populations are susceptible to complications due to malaria infection,
      particularly in malaria caused by Plasmodium falciparum. However, Plasmodium
      vivax the predominant Plasmodium spp. in Venezuela can also lead to severe
      malaria. METHODS: We reviewed retrospectively cases of malaria to identify the
      clinical features of those imported cases diagnosed at two institutions in
      Margarita Island (a non-endemic area), Venezuela, in an 8-year period. We
      conducted a retrospective observational study to identify the clinical and
      epidemiological features among hospitalized patients at Hospital Central and
      Hospital Agustin Hernandez with malaria acquired at malaria-endemic locations.
      RESULTS: We identified eighteen imported cases of malaria confirmed by thin and
      thick peripheral blood smears at these two institutions over an 8-year period.
      The mean age of diagnosis was 27 years. P. vivax was responsible for the majority
      of cases. All patients presented with fever, 89% with malaise, 78% with chills,
      and 67% with myalgia, among others symptoms. Mean haemoglobin levels on admission
      were 8.1g/dL (100% <12g/dL); platelets: 79,283cells/mm(3) (89% had platelets
      below 150,000); and a mean total leukocyte count: 3.4x10(3)cells/mm(3) (78% had
      leukopenia). Thirty nine percent of patients required blood transfusions. Two
      fatalities were identified (CFR=11%), one associated to severe malaria due to P.
      falciparum and the other due to a complicated case of P. vivax malaria.
      DISCUSSION: Imported cases of malaria due to P. vivax and P. falciparum in the
      studied population are associated with significant hematological complications.
      These findings illustrate the importance of educating non-immune populations
      about the malaria risk and prevention strategies; and from a pubic health
      perspective, the need to develop further malaria prevention strategies at a
      national level.

PMID- 19174302
TI  - Intestinal schistosomiasis, importation of a neglected tropical disease in
      Romania. Case report of a traveler to endemic regions.
AB  - BACKGROUND: Schistosomiasis is the second most common parasitic disease after
      malaria. Imported cases of schistosomiasis are reported in nonendemic regions due
      to an increased number of travelers to affected geographical areas. The present
      case report aimed to emphasize the importance of a correct history of a patient,
      including information regarding travel history and its consequences, and to
      overview the evolution of a tropical disease diagnosed rarely in Romania.
      MATERIALS AND METHODS: Retrospective analysis of a single case of imported
      schistosomiasis diagnosed in Timisoara, Romania. RESULT: A 25-year old male
      patient had traveled and worked abroad for a long period of time in tropical
      areas in Asia and South America (Brazil). The clinical pattern at admission to
      hospital included fever and diarrhea with multiple liquid stools with mucus.
      Physical examination was normal. Routine laboratory tests revealed an increased
      number of leucocytes. CONCLUSIONS: Final diagnosis was established with
      difficulty in this case. Failure to associate a febrile prolonged syndrome or
      chronic diarrhea with a history of travel can cause a delayed diagnosis.

PMID- 19174303
TI  - An imported case of Chikungunya fever from Madagascar: use of the sentinel
      traveller for detecting emerging arboviral infections in tropical and European
      countries.
AB  - A major Chikungunya virus (CHIKV) epidemic affected the South-Western Indian
      Ocean islands in 2005. This major outbreak raised concerns about the possibility
      of the emergence of CHIKV infections in Europe as an autochthonous CHIKV outbreak
      occurred in the Ravenna region of Italy during the summer of 2007 and was linked
      to a viraemic index case originating in Kerala, India. This report highlights the
      need for surveillance in countries where such emerging infections could be
      introduced by returning travellers.

PMID- 19174304
TI  - Comparison of electrospray and matrix-assisted laser desorption ionization on the
      same hybrid quadrupole time-of-flight tandem mass spectrometer: application to
      bidimensional liquid chromatography of proteins from bovine milk fraction.
AB  - Recently, two ionization sources, electrospray (ESI) and matrix-assisted laser
      desorption (MALDI) have been used in parallel to exploit their complementary
      nature and to increase proteome coverage. In this study, a method using
      bidimensional (2D) nanoLC coupled online with ESI quadrupole time-of-flight (Q
      TOF) with the simultaneous collection of fractions for analyses by LC-MALDI Q-TOF
      MS/MS was developed. A total of 39 bovine proteins were identified to a high
      degree of confidence. To help in differentiating peptide detection following ESI
      and MALDI with the same mass spectrometer, we compared physico-chemical
      characteristics of the peptides (molecular mass, charge and size) by principal
      component analysis (PCA) and analysis of variance on the results of PCA. More
      hydrophobic peptides with a wider mass coverage were identified when ESI was
      used, whereas more basic and smaller peptides were identified when MALDI was
      used. However, the generally accepted differentiation between ESI and MALDI
      according to the presence of basic amino acids residues Lys and Arg and the ratio
      Lys/Arg was not shown as significant in this study. Moreover, we pointed out the
      importance of the type of mass spectrometer used in complement to both ionization
      sources for achieving a global increase of proteome coverage.

PMID- 19174305
TI  - The impact of genome length on replication and genome stability of the
      herpesvirus guinea pig cytomegalovirus.
AB  - The impact of genome length on replication and genome stability was assessed for
      guinea pig cytomegalovirus (GPCMV), a member of the Herpesviridae. The 233-kb
      genome could be decreased by 15.1 kb without discernable impact on viral
      replication efficiency in vitro. Viruses with genomes under-length by up to 31 kb
      replicated with decreased efficiencies but this appeared to arise from the loss
      of augmenting viral genes rather than decreased genome length. Two deletions that
      were non-lethal on their own were lethal when combined, suggesting that the
      resulting 40.1 kb under-length genome fell below a minimum packageable size.
      Genomes over-length by 8.8 kb gave rise to spontaneous deletions just to the
      right of the major immediate early locus, the same region that undergoes
      deletions during fibroblast passage of human and rhesus cytomegaloviruses. These
      results suggest that genome integrity should be confirmed for herpesvirus mutants
      in which genome length is increased even modestly.

PMID- 19174306
TI  - Effect of different vasodilators on NTPDase activity in healthy and hypertensive
      patients.
AB  - INTRODUCTION: The thrombogenic process that affects the hypertensive patient is
      associated with regulatory mechanisms present in the vascular endothelium. These
      mechanisms involve release of an endothelium-derived relaxing factor,
      ectonucleotidase activity and calcium ion concentration. METHODS: Interference
      with ENTPDase activity in platelets of hypertensive patients and healthy donors
      was evaluated for arginine, sodium nitroprusside, and hydralazine. In addition,
      the kinetic behavior of NTPDase was determined in the presence of the vasodilator
      that showed the greatest inhibitory influence. RESULTS: Vasodilators decreased
      NTPDase activity with ATP and ADP as substrates. In controls, hydrolysis was
      increased in the presence of arginine. Captopril did not affect enzyme
      activities. The dose response for increasing sodium nitroprusside was biphasic.
      Kinetic behavior studies were estimated in the presence of sodium nitroprusside,
      which caused a mixed inhibition. The K(m) values increased and V(max) decreased
      with increasing sodium nitroprusside concentrations. The IC(50) and K(i) values
      indicated that the vasodilator was a strong NTPDase inhibitor when tested for the
      control and hypertensive group, using ATP and ADP as substrate, respectively.
      CONCLUSION: It is postulated that there was an interaction between vasodilators,
      NO donors and inhibition of NTPDase.

PMID- 19174307
TI  - Intraoperative margin assessment of the radical trachelectomy specimen.
AB  - OBJECTIVE: To summarize our experience in the frozen section (FS) assessment of
      the trachelectomy surgical margin. METHODS: All surgeries from 1994 to 2007 were
      performed by one surgeon. The FS examination was consistently carried out by a
      group of gynecologic pathologists according to the protocol described in details
      in this article. Cases were retrieved from the pathology files and the slides
      were reviewed by two pathologists. RESULTS: 132 patients were identified with
      complete pathology records. They ranged from 17 to 46 years old (median 31).
      Surgeries were performed for clinical Stages 1A (n=39) and 1B (n=93) tumors (63
      adenocarcinoma, 59 squamous cell carcinoma, 7 adenosquamous and 3 others). In 78
      cases, no residual tumor was seen in the trachelectomy specimens as it was
      resected by the preceding LEEP or cone. The margin was reported as negative in
      123, suspicious in 3 and positive in 6 cases. It was revised in 16 cases (6
      positive, 2 suspicious and 8 negative but <5 mm). Final margin assessment agreed
      with the FS diagnosis in 130 (98.5%) and showed interpretational overcall in 2
      cases (1.5%); only one of which resulted in a revised margin. No false negative
      intraoperative assessment was found. CONCLUSIONS: We describe our FS protocol and
      summarize our data. This protocol is reliable since none of the patients was
      under-treated.

PMID- 19174308
TI  - Demineralized dentin 3D porosity and pore size distribution using mercury
      porosimetry.
AB  - OBJECTIVES: The objectives of this study were to assess demineralized dentin
      porosity and quantify the different porous features distribution within the
      material using mercury intrusion porosimetry (MIP) technique. We compared
      hexamethyldisilazane (HMDS) drying and lyophilization (LYO) (freeze-drying) in
      sample preparation. METHODS: Fifty-six dentin discs were assigned into three
      groups. The control (CTR) group discs were superficially acid-etched (15s 37%
      H(3)PO(4)) to remove the smear layer and then freeze-dried whereas LYO and HMDS
      groups samples were first totally demineralized using EDTA 0.5M and then freeze
      dried and HMDS-dried respectively. MIP was used to determine open porosity and
      pore size distribution of each pair of samples. Field emission scanning electron
      microscopy (FESEM) was used to illustrate the results. RESULTS: The results
      showed two types of pores corresponding either to tubules and micro-branches or
      to inter-fibrillar spaces created by demineralization. Global porosity varied
      from 59% (HMDS-dried samples) to 70% (freeze-dried samples). Lyophilization
      drying technique seems to lead to less shrinkage than HMDS drying. FESEM revealed
      that collagen fibers of demineralized lyophilized samples are less melted
      together than in the HMDS-dried samples. SIGNIFICANCE: Demineralized dentin
      porosity is a key parameter in dentin bonding that will influence the hybrid
      layer quality. Its characterization could be helpful to improve the monomers
      infiltration.

PMID- 19174309
TI  - Administration of dehydroepiandrosterone ameliorates experimental autoimmune
      neuritis in Lewis rats.
AB  - Dehydroepiandrosterone (DHEA) is an abundant adrenal steroid in serum of humans,
      and has been reported to have anti-inflammatory, anti-proliferative, and certain
      immune-regulating properties. Experimental autoimmune neuritis (EAN) is a Th1
      cell-mediated animal model of Guillain-Barre syndrome (GBS) in humans. In the
      present study, DHEA was administered subcutaneously to Lewis rats immunized with
      bovine peripheral myelin (BPM) in Freund's complete adjuvant. Rats treated with
      DHEA displayed significant delay in onset, decreased inflammatory cell
      infiltration in the PNS. Benefit was associated with significant decreases in
      numbers of IFN-gamma and TNF-alpha expressing cells in the PNS, BPM-stimulated T
      cell proliferation and IFN-gamma, TNF-alpha-secretion in the spleen cells. Only 2
      mg DHEA-treated EAN rats decreased peak clinical score. No significant difference
      of supernatant IL-10 was found among the treatment and control groups. These
      results suggest that DHEA can ameliorate the severity of EAN by suppressing the
      proliferation of autoreactive T cell and expression of pro-inflammatory
      cytokines.

PMID- 19174311
TI  - Arterial hypertension parental burden affects arterial stiffness and wave
      reflection to the aorta in young offsprings.

PMID- 19174310
TI  - Administration of bone marrow stromal cells ameliorates experimental autoimmune
      myasthenia gravis by altering the balance of Th1/Th2/Th17/Treg cell subsets
      through the secretion of TGF-beta.
AB  - Bone marrow stromal cells (BMSCs) are strong candidates for cell therapy against
      human autoimmune diseases. Intravenous administration of syngenic BMSCs to EAMG
      model rats effectively ameliorated the disease, partially through a TGF-beta
      dependent mechanism. The proliferative ability of T or B cells from EAMG rats was
      inhibited by BMSCs at proper cocultured ratios. And the imbalance of Th1, Th2,
      Th17 and Treg cell subsets accompanied with the development of EAMG was corrected
      by the administration of BMSCs. These results provide further insights into the
      pathogenesis of MG, EAMG, and other immune-mediated diseases, and support a
      potential role for BMSCs in their treatment.

PMID- 19174312
TI  - The oxygen uptake efficiency slope is reduced in older patients with heart
      failure and a normal ejection fraction.

PMID- 19174313
TI  - From trivial headache to life-threatening disease.
AB  - Sometimes, a clinical course that initially appears to be 'classic' turns out to
      be a manifestation of a rare disease. We report on a 62-year-old woman who
      presented initially with episodic headache, followed by cardiogenic shock. What
      was first thought to be an ST-segment elevation acute myocardial infarction,
      later to be a takostubo cardiomyopathy, finally appeared to be a catecholamine
      induced cardiomyopathy due to a pheochromocytoma. This case illustrates that in a
      patient with presumed takotsubo cardiomyopathy and episodic headache, sweating,
      hypertension or tachycardia, pheochromocytoma needs to be excluded.

PMID- 19174314
TI  - Role of the R1135H KCNH2 mutation in Brugada syndrome.

PMID- 19174315
TI  - Intracoronary adiponectin levels rapidly and significantly increase after
      coronary revascularization.

PMID- 19174316
TI  - Effects of statins on vascular endothelial function in hypercholesterolemic
      patients with type 2 diabetes mellitus: fluvastatin vs. rosuvastatin.

PMID- 19174317
TI  - Drug eluting stent-induced Kounis syndrome.
AB  - Kounis syndrome is the concurrence of acute coronary syndromes with allergic
      conditions like anaphylaxis or anaphylactoid reactions. Cases of hypersensitivity
      to drugs-eluting-stent (DES) components able to cause serious clinical sequelae,
      like stent thrombosis have been reported recently. We report a case of a 50-year
      old male, allergic to larvae of fly carvaria, who, after exposure to the
      allergen, developed an acute myocardial infarction due to stent thrombosis,
      despite optimal medical therapy. To our knowledge this is the first description
      of intra-stent thrombosis associated with Kounis syndrome. The clinical
      implications and physiopathology of this association are discussed.

PMID- 19174318
TI  - Estimate of the abundance of cardiomyopathic mutations in the beta-myosin gene.

PMID- 19174319
TI  - Safety issues of adjunctive clopidogrel in patients discharged after percutaneous
      coronary intervention with stent placement and requiring oral anticoagulation.
AB  - Indications for percutaneous coronary intervention with stent placement are
      increasing; some candidates already require oral anticoagulation. Safety of
      triple antithrombotic therapy--aspirin (ASA), clopidogrel and oral
      anticoagulation (OAC)--remains largely unknown. In order to study hemorrhagic
      complications in those patients, we identified thirty-three patients from our
      anticoagulation clinic registry who were prescribed triple antithrombotic
      therapy. All hemorrhagic events were collected and classified as non-severe (NSH)
      or severe (SH). The same population provided a control to determine increased
      risk from addition of a second antiplatelet drug. Overall, patients were followed
      for 53 patient-months while on triple therapy (TT) and 869 patient-months on
      double therapy. Patients in TT group had more hemorrhages (90.6% patient-years vs
      8.29% patient-years, p<0.01) due to an increase in NSH (90.6% patient-years vs
      5.52% patient-years, p<0.01), without changes in SH. Mean international
      normalized ratio (INR) was similar in both groups and INR at bleeding time was
      not uniformly increased. We conclude that in patients with an AAS and OAC based
      regimen, addition of clopidogrel because of a stent placement results in a
      significant increase in NSH but no increase in SH.

PMID- 19174320
TI  - Premature coronary artery disease in young patients: an uncommon but growing
      entity.

PMID- 19174321
TI  - Associations among state and local organizational contexts: Use of evidence-based
      practices in the criminal justice system.
AB  - This study used hierarchical linear modeling (HLM) to examine the extent to which
      the organizational characteristics of state corrections agencies and local
      criminal justice facilities interacted in their associations with the extent to
      which local facilities are using evidence-based substance abuse treatment
      practices (EBPs). The study used data collected from two nationally
      representative surveys - one of state executives and the other of local prison
      wardens, justice administrators, and treatment directors - which were conducted
      as part of the National Criminal Justice Treatment Practices survey [NCJTP;
      Taxman, F.S., Young, D., Wiersema, B., Mitchell, S., Rhodes, A.G., 2007. The
      National Criminal Justice Treatment Practices Survey: Multi-level survey methods
      and procedures. J. Subst. Abuse Treat. 32, 225-238], and includes both adult
      criminal and juvenile justice samples. Results indicated that several state
      organizational characteristics were either associated with more EBP use or
      interacted with local organizational characteristics in associations with EBP
      use, including: (1) systems integration at the state level was associated with
      greater EBP use; (2) state staffing adequacy and stability accentuated the
      association between local training and resources for new programs and EBP use
      (i.e., in states with better staffing, the relationship between
      training/resources and EBP use in local facilities was stronger); and (3) state
      executives' attitudes regarding the missions and goals of corrections tended to
      diminish the extent to which corresponding local administrator attitudes were
      associated with EBP use. The study has implications for future research focused
      on EBP diffusion and implementation in correctional environments, particularly
      attempts to influence EBP use by working through state agencies.

PMID- 19174323
TI  - Tigecycline has no effect on cytokine release in an ex vivo endotoxin model of
      human whole blood.
AB  - In previous studies, tetracyclines have been shown to decrease the release of
      cytokines in experimental settings of endotoxaemia. Tigecycline is the first
      member of the closely related glycylglycines and, due to its broad antimicrobial
      spectrum, it is considered useful in the treatment of sepsis. We therefore tested
      its ability to influence the concentrations of the proinflammatory cytokines
      interleukin (IL)-1beta, tumour necrosis factor-alpha (TNFalpha) and IL-6 in an
      established ex vivo model of human endotoxaemia. Whole blood from ten healthy
      volunteers was incubated with either saline (negative control), tigecycline (1
      microg/mL [therapeutic concentration] or 100 microg/mL [supratherapeutic
      concentration]), lipopolysaccharide (LPS; 50 pg/mL, control) or a combination of
      tigecycline plus LPS (test group). Concentrations of IL-1beta, TNFalpha and IL-6
      in the supernatant were measured using commercially available enzyme-linked
      immunosorbent assay (ELISA) kits. As expected, incubation with LPS significantly
      increased the cytokine concentrations in whole blood compared with baseline
      (P<0.05). The combination of tigecycline plus LPS did not exert any significant
      effect on the concentrations of IL-1beta, IL-6 and TNFalpha after 2h and 4h of
      incubation compared with LPS alone. These results indicate that proinflammatory
      cytokines remained unaffected by tigecycline in an established ex vivo model of
      systemic inflammatory response.

PMID- 19174322
TI  - Childhood trauma and prodromal symptoms among individuals at clinical high risk
      for psychosis.
AB  - INTRODUCTION: Numerous studies point to an association between childhood trauma
      and the later development of psychotic illness. However, little is known about
      the prevalence of childhood trauma and its relationship to attenuated positive
      and other symptoms in individuals at heightened clinical risk for psychosis.
      METHOD: Thirty clinical high-risk patients (83% male, 43% Caucasian, and with a
      mean age of 19) were ascertained from the New York metropolitan area and
      evaluated for prodromal and affective symptoms, and queried regarding experiences
      of childhood trauma and abuse. RESULTS: Ninety-seven percent endorsed at least
      one general trauma experience, 83% reported physical abuse, 67% emotional abuse,
      and 27% sexual abuse. As hypothesized, total trauma exposure was positively
      associated with severity of attenuated positive symptoms (in particular
      grandiosity), an effect primarily accounted for by ethnic minority participants,
      who reported greater exposure to trauma. Trauma exposure was related to affective
      symptoms only in the Caucasian subgroup. CONCLUSIONS: Childhood trauma was
      commonly self-reported, especially among clinical high-risk patients from ethnic
      minorities, for whom trauma was related to positive symptoms. Future areas of
      research include an evaluation of potential mechanisms for this relationship,
      including neuroendocrine and subcortical dopaminergic function.

PMID- 19174324
TI  - Host-microbe interactions: bacteria.

PMID- 19174325
TI  - The state of the evidence for computerized provider order entry: a systematic
      review and analysis of the quality of the literature.
AB  - OBJECTIVE: This paper presents the results of a systematic literature review and
      a formal analysis of the scientific quality of empirical research on computerized
      provider order-entry (CPOE) applications. DESIGN: Formal, systematic review
      techniques were used to search the literature, determine study relevance, and
      evaluate study quality. MEASUREMENT: A search of multiple databases from 1976
      through mid-2007 yielded a final set of 46 articles. Relevance criteria included:
      (1) a direct comparison of a CPOE system with a non-CPOE system; (2)
      implementation in a clinical setting; and (3) clinically relevant outcomes.
      RESULTS: Study quality varied widely. Three major areas were identified for
      improvement in future studies: (1) internal validity, especially in terms of
      study designs, blinding, and instrumentation bias; (2) construct validity of the
      phenomenon of CPOE itself; and (3) measurement strategies, including reliability
      and validity assessments. CONCLUSIONS: The evidence for the impact of CPOE needs
      to be improved to support scientific generalizability. Several common confounds
      are found in this literature. Future researchers will want to address them to
      improve the strength of the inference between CPOE and clinical outcomes.
      Discussion focuses on methods to improve future CPOE research.

PMID- 19174327
TI  - Simultaneous characterization of optical and rheological properties of carotid
      arteries via bimodal spectroscopy: experimental and simulation results.
AB  - This study aimed at identifying potential correlations between rheological and
      optical properties of carotid artery rings before and after cryopreservation at
      different mechanical deformations using experimental and simulation results.
      Therefore, a uniaxial mechanical test bench was coupled to fibered optical
      spectroscopes measuring 410 nm excited autofluorescence and 650-850 nm
      elastically backscattered intensity spectra. Furthermore, we developed a
      statistical simulation program of light transport and fluorescence adapted to our
      specific experimental configuration. Both spectroscopies gave intensity spectra
      with higher amplitude for the cryopreserved samples. These observations are to be
      related to histological modifications affecting the arterial wall of
      postcryopreserved samples. We also observed significant spectral amplitude
      variations (increasing autofluorescence intensity and decreasing diffuse
      reflectance) as a function of the circumferential strains (0%-60%). Due to
      simulation, we identified values of absorption, diffusion, and anisotropy
      coefficients, and their variations as a function of state (fresh-cryopreserved),
      strains (0, 30%, 60%), and wavelengths (700, 740, 780 nm). The media and the
      adventice are, respectively, less and more absorbing for postcryopreserved rings,
      and it is the opposite for the fresh ones at higher wavelengths. Absorption and
      diffusion coefficients are slightly higher, whatever the wavelengths and strains,
      for the fresh than for the cryopreserved samples.

PMID- 19174328
TI  - Magnetic maneuvering of endoscopic capsules by means of a robotic navigation
      system.
AB  - The use of video capsules for noninvasive explorations of the digestive tube is
      progressively increasing today. At present, the motion of these wireless
      endoscopic devices cannot be controlled and they proceed by means of visceral
      peristalsis and gravity. Aimed at enabling a motion control, the technique
      described here uses an external magnetic field applied to the video capsule,
      previously coated with a magnetic shell. As a source of controlled magnetic
      field, a robotic magnetic navigation system, recently introduced in the clinical
      practice to magnetically steer cardiovascular interventional devices, was
      suggested in a previous study to be deserving of investigation. The attractive
      potentialities of this system, along with its current limitations, in order to
      maneuver endoscopic capsules were studied in this work for the first time, both
      from a theoretical and an experimental point of view. The actual capabilities
      were experimentally assessed with preliminary motion control tests on a
      conventional video capsule inside a human-sized plastic phantom. Results
      demonstrated the possibility of achieving controlled magnetic maneuvers within
      the considered environment.

PMID- 19174326
TI  - Evidence for dendritic cell-dependent CD4(+) T helper-1 type responses to
      commensal bacteria in normal human intestinal lamina propria.
AB  - Reactivity of lamina propria (LP) T cells to commensal bacteria has been
      demonstrated in animal models of inflammatory bowel disease (IBD) and in humans
      with IBD, but few studies have evaluated the function of such cells in normal
      individuals. LP mononuclear cells (LPMC) were disaggregated from healthy human
      intestinal tissue and cultured with heat-killed commensal and pathogenic
      bacteria. CD3(+)CD4(+) IFN-gamma-producing (Th1) cells reactive to commensal
      bacteria were demonstrated at frequencies ranging from 0.05 to 2.28% in LPMC.
      Bacteria-specific Th1 responses were inhibited by anti-HLA-DR antibodies and
      chloroquine exposure, were enriched in LP relative to peripheral blood, and
      expressed effector memory cell markers. Bacteria-specific CD4(+) T cell
      proliferation in vitro was dependent on the presence of LP dendritic cells (DCs),
      which produced pro-inflammatory cytokines upon bacterial exposure. These results
      suggest that bacteria-reactive DCs and CD4(+) T cells in normal LP have
      substantial pro-inflammatory potential that is revealed upon disaggregation in
      vitro.

PMID- 19174329
TI  - Sign language recognition using intrinsic-mode sample entropy on sEMG and
      accelerometer data.
AB  - Sign language forms a communication channel among the deaf; however, automated
      gesture recognition could further expand their communication with the hearers. In
      this work, data from five-channel surface electromyogram and 3-D accelerometer
      from the signer's dominant hand were analyzed using intrinsic-mode entropy (IMEn)
      for the automated recognition of Greek sign language (GSL) isolated signs.
      Discriminant analysis was used to identify the effective scales of the intrinsic
      mode functions and the window length for the calculation of the IMEn that
      contributes to the efficient classification of the GSL signs. Experimental
      results from the IMEn analysis applied to GSL signs corresponding to 60-word
      lexicon repeated ten times by three native signers have shown more than 93% mean
      classification accuracy using IMEn as the only source of the classification
      feature set. This provides a promising bed-set toward the automated GSL gesture
      recognition.

PMID- 19174330
TI  - 3-D gradient coil design--initial theoretical framework.
AB  - An analytic inverse method is presented for the theoretical design of 3-D
      transverse gradient coils. Existing gradient coil design methods require the
      basic geometry of the coil to be predetermined before optimization. Typically,
      coil windings are constrained to lie on cylindrical, planar, spherical, or
      conical surfaces. In this paper, a fully 3-D region in the solution space is
      explored and the precise geometry of the gradient coils is obtained as part of
      the optimization process. Primary interest lies in minimizing the field error
      between induced and target gradient fields within a spherical target region. This
      is achieved using regularization, in which the field error is minimized along
      with the total coil power, to obtain a 3-D current density solution within the
      coil volume. A novel priority streamline technique is used to create 3-D coil
      windings that approximate this current density, and a secondary optimization is
      performed to obtain appropriate coil currents. The 3-D coil windings display an
      interesting general geometric form involving sets of closed loops plus spiral
      type coils, and a number of examples are presented and discussed. The
      corresponding induced magnetic field is found to be highly linear within the
      region of interest, and a shielding constraint may be implemented to minimize the
      field outside the coil volume.

PMID- 19174331
TI  - Catheter kinematics for intracardiac navigation.
AB  - Steerable catheters are utilized frequently in minimally invasive cardiac
      interventions. Despite their extensive applications, the properties of the
      steerable section of such devices have not been thoroughly investigated. In this
      paper, the kinematics of the distal shaft of the catheters is modeled, and the
      catheter's reachable workspace and its singular configurations are studied. The
      modeling is empirically validated through experiments with actual catheters
      mounted on a specialized robot. The statistical analysis of the experiments
      verify the effectiveness of the proposed model in estimating the catheter's tip
      position. In the experiments, the modeling error does not exceed 2.66 +/- 1.96
      mm, and the mean absolute error in position coordinates is less than 1.55 mm. In
      addition, the linear relationship between the model and the measured position
      vectors is demonstrated, and the significance of the modeling goodness of fit is
      established. Based on the precision and computational effectiveness of the
      method, the applicability of the modeling to control and simulation purposes is
      postulated.

PMID- 19174332
TI  - xDAWN algorithm to enhance evoked potentials: application to brain-computer
      interface.
AB  - A brain-computer interface (BCI) is a communication system that allows to control
      a computer or any other device thanks to the brain activity. The BCI described in
      this paper is based on the P300 speller BCI paradigm introduced by Farwell and
      Donchin . An unsupervised algorithm is proposed to enhance P300 evoked potentials
      by estimating spatial filters; the raw EEG signals are then projected into the
      estimated signal subspace. Data recorded on three subjects were used to evaluate
      the proposed method. The results, which are presented using a Bayesian linear
      discriminant analysis classifier , show that the proposed method is efficient and
      accurate.

PMID- 19174333
TI  - Model estimation of cerebral hemodynamics between blood flow and volume changes:
      a data-based modeling approach.
AB  - It is well known that there is a dynamic relationship between cerebral blood flow
      (CBF) and cerebral blood volume (CBV). With increasing applications of functional
      MRI, where the blood oxygen-level-dependent signals are recorded, the
      understanding and accurate modeling of the hemodynamic relationship between CBF
      and CBV becomes increasingly important. This study presents an empirical and data
      based modeling framework for model identification from CBF and CBV experimental
      data. It is shown that the relationship between the changes in CBF and CBV can be
      described using a parsimonious autoregressive with exogenous input model
      structure. It is observed that neither the ordinary least-squares (LS) method nor
      the classical total least-squares (TLS) method can produce accurate estimates
      from the original noisy CBF and CBV data. A regularized total least-squares
      (RTLS) method is thus introduced and extended to solve such an error-in-the
      variables problem. Quantitative results show that the RTLS method works very well
      on the noisy CBF and CBV data. Finally, a combination of RTLS with a filtering
      method can lead to a parsimonious but very effective model that can characterize
      the relationship between the changes in CBF and CBV.

PMID- 19174334
TI  - Least-square NUFFT methods applied to 2-D and 3-D radially encoded MR image
      reconstruction.
AB  - Radially encoded MRI has gained increasing attention due to its motion
      insensitivity and reduced artifacts. However, because its samples are collected
      nonuniformly in the k-space, multidimensional (especially 3-D) radially sampled
      MRI image reconstruction is challenging. The objective of this paper is to
      develop a reconstruction technique in high dimensions with on-the-fly kernel
      calculation. It implements general multidimensional nonuniform fast Fourier
      transform (NUFFT) algorithms and incorporates them into a k-space image
      reconstruction framework. The method is then applied to reconstruct from the
      radially encoded k-space data, although the method is applicable to any non
      Cartesian patterns. Performance comparisons are made against the conventional
      Kaiser-Bessel (KB) gridding method for 2-D and 3-D radially encoded computer
      simulated phantoms and physically scanned phantoms. The results show that the
      NUFFT reconstruction method has better accuracy-efficiency tradeoff than the KB
      gridding method when the kernel weights are calculated on the fly. It is found
      that for a particular conventional kernel function, using its corresponding
      deapodization function as a scaling factor in the NUFFT framework has the
      potential to improve accuracy. In particular, when a cosine scaling factor is
      used, the NUFFT method is faster than KB gridding method since a closed-form
      solution is available and is less computationally expensive than the KB kernel
      (KB griding requires computation of Bessel functions). The NUFFT method has been
      successfully applied to 2-D and 3-D in vivo studies on small animals.

PMID- 19174335
TI  - Fluid vector flow and applications in brain tumor segmentation.
AB  - In this paper, we propose a new approach that we call the "fluid vector flow"
      (FVF) active contour model to address problems of insufficient capture range and
      poor convergence for concavities. With the ability to capture a large range and
      extract concave shapes, FVF demonstrates improvements over techniques like
      gradient vector flow, boundary vector flow, and magnetostatic active contour on
      three sets of experiments: synthetic images, pediatric head MRI images, and brain
      tumor MRI images from the Internet brain segmentation repository.

PMID- 19174336
TI  - Microwave imaging for early breast cancer detection using a shape-based strategy.
AB  - In this paper, we propose and analyze a novel shape reconstruction technique for
      the early detection of breast cancer from microwave data, which is based on a
      level-set technique. The shape-based approach offers several advantages compared
      to more traditional pixel-based approaches when targeting the reconstruction of
      key characteristics of a hidden tumor such as its correct size, shape, and static
      permittivity value. In addition to these key characteristics of hidden tumors, we
      aim at estimating the correct interfaces between fatty and fibroglandular tissue
      in the breast and their internal permittivity profiles. The level set strategy
      (which is an implicit representation of the shapes) frees us from topological
      restrictions when reconstructing an a priori arbitrary number of tumors and the
      often quite complicated interfaces between fatty and fibroglandular regions. The
      presented strategy is able to detect and, in most cases, characterize tumors
      whose sizes (diameters) are much smaller than the wavelengths of the
      electromagnetic waves that are used for illuminating the breast. We present
      numerical results for a 2-D model with two distinct tissue types (fatty and
      fibroglandular) in the interior of the breast (in addition to a possible tumor
      and the surrounding skin). Our results demonstrate the performance and potential
      of our scheme in various simulated but realistic situations.

PMID- 19174338
TI  - Assessment of tear film surface quality using dynamic-area high-speed
      videokeratoscopy.
AB  - A new method for noninvasive assessment of tear film surface quality (TFSQ) is
      proposed. The method is based on high-speed videokeratoscopy in which the corneal
      area for the analysis is dynamically estimated in a manner that removes
      videokeratoscopy interference from the shadows of eyelashes but not that related
      to the poor quality of the precorneal tear film that is of interest. The
      separation between the two types of seemingly similar videokeratoscopy
      interference is achieved by region-based classification in which the overall
      noise is first separated from the useful signal (unaltered videokeratoscopy
      pattern), followed by a dedicated interference classification algorithm that
      distinguishes between the two considered interferences. The proposed technique
      provides a much wider corneal area for the analysis of TFSQ than the previously
      reported techniques. A preliminary study with the proposed technique, carried out
      for a range of anterior eye conditions, showed an effective behavior in terms of
      noise to signal separation, interference classification, as well as consistent
      TFSQ results. Subsequently, the method proved to be able to not only discriminate
      between the bare eye and the lens on eye conditions but also to have the
      potential to discriminate between the two types of contact lenses.

PMID- 19174340
TI  - An improved technique to predict the time-of-arrival of a tumor response in radar
      based breast imaging.
AB  - Radar-based microwave imaging has been proposed as a complementary modality for
      early-stage breast cancer screening. This paper presents an algorithm that may be
      used to accurately predict the time-of-arrival (TOA) of a tumor response
      contained in sample data acquired from a small number of antennas in a realistic
      scenario. The TOA information may be used by many of the existing radar-based
      methods to detect and localize a tumor response. The robustness of the algorithm
      is demonstrated with data generated from realistic numerical breast models.

PMID- 19174339
TI  - Multiscale entropy analysis of EEG for assessment of post-cardiac arrest
      neurological recovery under hypothermia in rats.
AB  - Neurological complications after cardiac arrest (CA) can be fatal. Although
      hypothermia has been shown to be beneficial, understanding the mechanism and
      establishing neurological outcomes remains challenging because effects of CA and
      hypothermia are not well characterized. This paper aims to analyze EEG (and the
      alpha-rhythms) using multiscale entropy (MSE) to demonstrate the ability of MSE
      in tracking changes due to hypothermia and compare MSE during early recovery with
      long-term neurological examinations. Ten Wistar rats, upon post-CA resuscitation,
      were randomly subjected to hypothermia (32 degrees C-34 degrees C, N = 5) or
      normothermia (36.5 degrees C-37.5 degrees C, N = 5). EEG was recorded and
      analyzed using MSE during seven recovery phases for each experiment: baseline,
      CA, and five early recovery phases (R1-R5). Postresuscitation neurological
      examination was performed at 6, 24, 48, and 72 h to obtain neurological deficit
      scores (NDSs). Results showed MSE to be a sensitive marker of changes in alpha
      rhythms. Significant difference (p < 0.05) was found between the MSE for two
      groups during recovery, suggesting that MSE can successfully reflect temperature
      modulation. A comparison of short-term MSE and long-term NDS suggested that MSE
      could be used for predicting favorability of long-term outcome. These experiments
      point to the role of cortical rhythms in reporting early neurological response to
      ischemia and therapeutic hypothermia.

PMID- 19174341
TI  - Information capacity of the thumb and the index finger in communication.
AB  - Due to its large number of degrees of freedom and extensive connection to the
      brain, the human hand has been used to create channels of communication for a
      variety of human-machine systems. However, a fundamental question about the hand
      channel is still unanswered: what is its information capacity? This study aims to
      provide quantitative indication of effectiveness of the hand as a communication
      channel. We estimated that per gesture, the thumb and the index finger may
      deliver at most 10 and 7 bits of information, respectively. Based on this, we
      derived an upper bound for the information capacity of the hand in gesture-based
      communication: 150 b/s. Knowing this bound is critical to evaluating the
      potential and limitation of the hand channel for various forms of human-machine
      interactions.

PMID- 19174342
TI  - A texture-based classification of crackles and squawks using lacunarity.
AB  - An automatic classification method to efficiently discriminate the types of
      discontinuous breath sounds (DBSs), i.e., fine crackles (FCs), coarse crackles
      (CC), and squawks (SQ), is presented in this paper. Using the lacunarity of the
      acquired DBS, the proposed classification method, namely LAC, introduces a
      texture-based approach that captures the differences in the distribution of FC,
      CC, and SQ across the breathing cycle, which may lead to more accurate
      characterization of the pulmonary acoustical changes due to the related
      pathology. Prior to the lacunarity analysis, wavelet-based denoising of DBS is
      employed to eliminate effects of the vesicular sound (background noise) to DBS
      oscillatory pattern. LAC analysis builds its classification power both upon the
      use of lacunarity at an optimum scale and the approximation of its trajectory
      across an optimum range of scales using a three-parameter hyperbola model. LAC is
      applied to 363 DBS corresponding to 25 cases included in four lung sound
      databases. Results show that LAC efficiently classifies the three DBS categories
      in the comparison groups of FC-CC, FC-SQ (both with mean accuracy of 100%), CC-SQ
      (mean accuracy of 99.62%-100%), and FC-CC-SQ (mean accuracy of 99.75%-100%). When
      compared to other classification tools, LAC seems quite attractive, since,
      without employing high computational complexity, it results in high
      classification accuracy. Moreover, LAC introduces a "texture" concept in the
      analysis of breath sounds, something that strongly relates to the perception of
      the bioacoustic signals by the physician. Due to its simplicity, LAC could be
      implemented in a real-time context and be used in clinical medicine as a module
      of an integrated intelligent patient evaluation system.

PMID- 19174343
TI  - MR measurement of cerebrospinal fluid velocity wave speed in the spinal canal.
AB  - Noninvasive measurement of the speed with which the cerebrospinal fluid (CSF)
      velocity wave travels through the spinal canal is of interest as a potential
      indicator of CSF system pressure and compliance, both of which may play a role in
      the development of craniospinal diseases. However, measurement of CSF velocity
      wave speed (VWS) has eluded researchers primarily due to either a lack of access
      to CSF velocity measurements or poor temporal resolution. Here, we present a CSF
      VWS measurement methodology using a novel MR sequence that acquires unsteady
      velocity measurements during the cardiac cycle with a time interval < 10 ms.
      Axial CSF velocity measurements were obtained in the sagittal plane of the
      cervical spinal region on three subjects referred for an MRI scan without
      craniospinal disorders. CSF VWS was estimated by using the time shift identified
      by the maximum velocity and maximum temporal velocity gradient during the cardiac
      cycle. Based on the maximum velocity gradient, the mean VWS in the three cases
      was calculated to be 4.6 m/s (standard deviation 1.7 m/s, p < 0.005) during
      systolic acceleration. VWS computed using maximum velocity alone was not
      statistically significant for any of the three cases. The measurements of VWS are
      close in magnitude to previously published values. The methodology represents a
      new technique that can be used to measure VWS in the spinal canal noninvasively.
      Further research is required to both validate the measurements and determine
      clinical significance.

PMID- 19174344
TI  - A nonlinear total variation-based denoising method with two regularization
      parameters.
AB  - The aim of the present paper is to study the effect of the regularization
      parameter used in the numerical implementation of the Rudin-Osher-Fatemi
      denoising model. By using two different regularization parameters in the
      numerical scheme of the Rudin-Osher-Fatemi model, we will show experimentally
      that when a particular relationship between the sizes of these parameters holds,
      the quality of the denoised image and the speed of convergence of the numerical
      scheme are both much improved in comparison with the classic numerical scheme of
      the Rudin-Osher-Fatemi model where only one regularization parameter is used.

PMID- 19174345
TI  - A real-time compliance mapping system using standard endoscopic surgical forceps.
AB  - In endoscopic surgery, the use of long surgical instruments through access ports
      diminishes tactile feedback and degrades the surgeon's ability to identify hidden
      tissue abnormalities. To overcome this constraint, we developed a real-time
      compliance mapping system that is composed of: 1) a standard surgical instrument
      with a high-precision sensor configuration design; 2) real-time objective
      interpretation of the output signals for tissue identification; and 3) a novel
      human-computer interaction technique using interactive voice and handle force
      monitoring techniques to suit operating theater working environment. The system
      was calibrated and used in clinical practice in four routine endoscopic human
      procedures. In a laboratory-based experiment to compare the tissue discriminatory
      power of the system with that of surgeons' hands, the system's tissue
      discriminatory power was three times more sensitive and 10% less specific. The
      data acquisition precision was tested using principal component analysis (R(2)X =
      0.975, Q2 [cumulative (cum)] = 0.808 ) and partial least square discriminate
      analysis (R(2)X = 0.903, R(2)Y = 0.729, Q2 (cum) = 0.572).

PMID- 19174346
TI  - Instrumentation of the loss-of-resistance technique for epidural needle
      insertion.
AB  - Epidural anesthesia is the most common form of anesthesia in obstetrics. The loss
      of-resistance to saline injection is used to confirm when the needle tip enters
      the epidural space. This procedure is highly dependent on skill and expertise, so
      it is useful to quantify the tissue resistance during insertion. Sensors are used
      to measure the force and displacement of the plunger of the syringe and the
      pressure at the needle tip. A model is also developed to estimate the pressure
      from the force and displacement. Tests are first performed on porcine tissue to
      compare the continuous-pressure and intermittent-pressure versions of the
      technique and to compare the paramedian and midline needle approaches. The
      accuracy of the pressure model is 12% of peak pressure for the continuous
      technique and 20% for the intermittent technique. Significant differences in
      injection flow rate were also found for the muscle, interspinous ligament, and
      ligamentum flavum encountered in the two approaches. A small clinical study on
      human subjects was performed and again significant differences were found in flow
      rate for different tissues. These quantitative results improve the understanding
      of small differences in feel that have been previously known qualitatively and
      may help in the development of simulators.

PMID- 19174347
TI  - Ambulatory estimation of center of mass displacement during walking.
AB  - The center of mass (CoM) and the center of pressure (CoP) are two variables that
      are crucial in assessing energy expenditure and stability of human walking. The
      purpose of this study is to estimate the CoM displacement continuously using an
      ambulatory measurement system. The measurement system consists of instrumented
      shoes with 6 DOF force/moment sensors beneath the heels and the forefeet.
      Moreover, two inertial sensors are rigidly attached to the force/moment sensors
      for the estimation of position and orientation. The estimation of CoM
      displacement is achieved by fusing low-pass filtered CoP data with high-pass
      filtered double integrated CoM acceleration, both estimated using the
      instrumented shoes. Optimal cutoff frequencies for the low-pass and high-pass
      filters appeared to be 0.2 Hz for the horizontal direction and 0.5 Hz for the
      vertical direction. The CoM estimation using this ambulatory measurement system
      was compared to CoM estimation using an optical reference system based on the
      segmental kinematics method. The rms difference of each component of the CoM
      displacement averaged over a hundred trials obtained from seven stroke patients
      was ( 0.020 +/-0.007 ) m (mean +/- standard deviation) for the forward x
      direction, ( 0.013 +/-0.005) m for the lateral y-direction, and ( 0.007 +/-0.001)
      m for the upward z-direction. Based on the results presented in this study, it is
      concluded that the instrumented shoe concept allows accurate and continuous
      estimation of CoM displacement under ambulatory conditions.

PMID- 19174348
TI  - Accuracy of ultrasound measurements for skull bone thickness using coded signals.
AB  - The knowledge of skull bone thickness would be helpful for a great variety of
      surgical interventions of the head. Ultrasound (US) can offer this information
      intraoperatively in real time. A-mode US measurements of skull bone thickness
      were performed with different pulse characteristics: 1) in water and 2) by
      directly coupling a 2.25-MHz US transducer integrated in a handpiece with a soft
      delay line using coded excitation (CE) (SonoPointer). Mechanical measurements by
      calipers served as controls. The specimen were 16 nonselected human cadaveric
      skull bones preserved with formaldehyde. The average difference between the bone
      thickness measured by the SonoPointer and the mechanical control measurements was
      0.04 +/- 0.62 mm. The 95% limits of agreement between the two methods were -1.18
      and 1.25 mm. However, even the gold standard of two repeated caliper measurements
      had limits of agreement of -0.4 and 0.42 mm. Using a standard US pulse in water,
      only 62.5% sample points were measurable, whereas the SonoPointer produced the
      thickness measurement in 97.9% of points. CE proved to be superior to single
      burst or needle US pulses. A-mode US measurements of skull bone thickness using
      the SonoPointer are feasible. It may provide valuable information on skull bone
      thickness, e.g., for osteosynthesis, calvarial split bone harvesting,
      implantation of hearing devices, osseointegrated titanium fixtures, and skull
      base surgery.

PMID- 19174349
TI  - Computer-aided detection of bleeding regions for capsule endoscopy images.
AB  - Capsule endoscopy (CE) has been widely used to diagnose diseases in human
      digestive tract. However, a tough problem of this new technology is that too many
      images to be inspected by eyes cause a huge burden to physicians, so it is
      significant to investigate computerized diagnosis methods. In this paper, a new
      computer-aided system aimed for bleeding region detection in CE images is
      proposed. This new system exploits color texture feature, an important clue used
      by physicians, to analyze status of gastrointestinal tract. We put forward a new
      idea of chrominance moment as the color part of color texture feature, which
      makes full use of Tchebichef polynomials and illumination invariant of
      hue/saturation/intensity color space. Combined with uniform local binary pattern,
      a current texture representation model, it can be applied to discriminate normal
      regions and bleeding regions in CE images. Classification of bleeding regions
      using multilayer perceptron neural network is then deployed to verify performance
      of the proposed color texture features. Experimental results on our bleeding
      image data show that the proposed scheme is promising in detecting bleeding
      regions.

PMID- 19174350
TI  - Decentralized robust adaptive control for the multiagent system consensus problem
      using neural networks.
AB  - A robust adaptive control approach is proposed to solve the consensus problem of
      multiagent systems. Compared with the previous work, the agent's dynamics
      includes the uncertainties and external disturbances, which is more practical in
      real-world applications. Due to the approximation capability of neural networks,
      the uncertain dynamics is compensated by the adaptive neural network scheme. The
      effects of the approximation error and external disturbances are counteracted by
      employing the robustness signal. The proposed algorithm is decentralized because
      the controller for each agent only utilizes the information of its neighbor
      agents. By the theoretical analysis, it is proved that the consensus error can be
      reduced as small as desired. The proposed method is then extended to two cases:
      Agents form a prescribed formation, and agents have the higher order dynamics.
      Finally, simulation examples are given to demonstrate the satisfactory
      performance of the proposed method.

PMID- 19174351
TI  - Markovian search games in heterogeneous spaces.
AB  - In this paper, we consider how to search for a mobile evader in a large
      heterogeneous region when sensors are used for detection. Sensors are modeled
      using probability of detection. Due to environmental effects, this probability
      will not be constant over the entire region. We map this problem to a graph
      search problem, and even though deterministic graph search is NP-complete, we
      derive a tractable optimal probabilistic search strategy. We do this by defining
      the problem as a dynamic game played on a Markov chain. We prove that this
      strategy is optimal in the sense of Nash. Simulations of an example problem
      illustrate our approach and verify our claims.

PMID- 19174352
TI  - Information-driven search strategies in the board game of CLUE.
AB  - This paper presents an information-driven sensor management problem, referred to
      as treasure hunt, which is relevant to mobile-sensor applications such as mine
      hunting, monitoring, and surveillance. The objective is to infer a hidden
      variable or treasure by selecting a sequence of measurements associated with
      multiple fixed targets distributed in the sensor workspace. The workspace is
      represented by a connectivity graph, where each node represents a possible sensor
      deployment, and the arcs represent possible sensor movements. An additive
      conditional entropy reduction function is presented to efficiently compute the
      expected benefit of a measurement sequence over time. Then, the optimal treasure
      hunt strategy is determined by a novel label-correcting algorithm operating on
      the connectivity graph. The methodology is illustrated through the board game of
      CLUE, which is shown to be a benchmark example of the treasure hunt problem. The
      game results show that a computer player implementing the strategies developed in
      this paper outperforms players implementing Bayesian networks, Q-learning, or
      constraint satisfaction, as well as human players.

PMID- 19174353
TI  - Manifold-based learning and synthesis.
AB  - This paper proposes a new approach to analyze high-dimensional data set using low
      dimensional manifold. This manifold-based approach provides a unified formulation
      for both learning from and synthesis back to the input space. The manifold
      learning method desires to solve two problems in many existing algorithms. The
      first problem is the local manifold distortion caused by the cost averaging of
      the global cost optimization during the manifold learning. The second problem
      results from the unit variance constraint generally used in those spectral
      embedding methods where global metric information is lost. For the out-of-sample
      data points, the proposed approach gives simple solutions to transverse between
      the input space and the feature space. In addition, this method can be used to
      estimate the underlying dimension and is robust to the number of neighbors.
      Experiments on both low-dimensional data and real image data are performed to
      illustrate the theory.

PMID- 19174354
TI  - Generalized fuzzy C-means clustering algorithm with improved fuzzy partitions.
AB  - The fuzziness index m has important influence on the clustering result of fuzzy
      clustering algorithms, and it should not be forced to fix at the usual value m =
      2. In view of its distinctive features in applications and its limitation in
      having m = 2 only, a recent advance of fuzzy clustering called fuzzy c-means
      clustering with improved fuzzy partitions (IFP-FCM) is extended in this paper,
      and a generalized algorithm called GIFP-FCM for more effective clustering is
      proposed. By introducing a novel membership constraint function, a new objective
      function is constructed, and furthermore, GIFP-FCM clustering is derived.
      Meanwhile, from the viewpoints of L(p) norm distance measure and competitive
      learning, the robustness and convergence of the proposed algorithm are analyzed.
      Furthermore, the classical fuzzy c-means algorithm (FCM) and IFP-FCM can be taken
      as two special cases of the proposed algorithm. Several experimental results
      including its application to noisy image texture segmentation are presented to
      demonstrate its average advantage over FCM and IFP-FCM in both clustering and
      robustness capabilities.

PMID- 19174355
TI  - Microvascular flow estimation by contrast-assisted ultrasound B-scan and
      statistical parametric images.
AB  - The microbubbles destruction/replenishment technique has been previously applied
      to estimating blood flow in the microcirculation. The rate of increase of the
      time-intensity curve (TIC) due to microbubbles flowing into the region of
      interest (ROI), as measured from B-mode images, closely reflects the flow
      velocity. In previous studies, we proposed a new approach called the time
      Nakagami-parameter curve (TNC) obtained from Nakagami images to monitor
      microbubble replenishment for quantifying the microvascular flow velocity. This
      study aimed to further explore some effects that may affect the TNC to estimate
      the microflow, including microbubble concentration, ultrasound transmitting
      energy, attenuation, intrinsic noise, and tissue clutter. In order to well
      control each effect production, we applied a typical simulation method to
      investigate the TIC and TNC. The rates of increase of the TIC and TNC were
      expressed by the rate constants beta(I) and beta(N), respectively, of a
      monoexponential model. The results show that beta(N) quantifies the microvascular
      flow velocity similarly to the conventional beta(I) . Moreover, the measures of
      beta(I) and beta(N) are not influenced by microbubble concentration, transducer
      excitation energy, and attenuation effect. Although the effect of intrinsic
      signals contributed by noise and blood would influence the TNC behavior, the TNC
      method has a better tolerance of tissue clutter than the TIC does, allowing the
      presence of some clutter components in the ROI. The results suggest that the TNC
      method can be used as a complementary tool for the conventional TIC to reduce the
      wall filter requirements for blood flow measurement in the microcirculation.

PMID- 19174356
TI  - A telehealth architecture for networked embedded systems: a case study in in vivo
      health monitoring.
AB  - The improvement in processor performance through continuous breakthroughs in
      transistor technology has resulted in the proliferation of lightweight embedded
      systems. Advances in wireless technology and embedded systems have enabled remote
      healthcare and telemedicine. While medical examinations could previously extract
      only localized symptoms through snapshots, now continuous monitoring can
      discretely analyze how a patient's lifestyle affects his/her physiological
      conditions and if additional symptoms occur under various stimuli. We demonstrate
      how medical applications in particular benefit from a hierarchical networking
      scheme that will improve the quantity and quality of ubiquitous data collection.
      Our Telehealth networking infrastructure provides flexibility in terms of
      functionality and the type of applications that it supports. We specifically
      present a case study that demonstrates the effectiveness of our networked
      embedded infrastructure in an in vivo pressure application. Experimental results
      of the in vivo system demonstrate how it can wirelessly transmit pressure
      readings measuring from 0 to 1.5 lbf/in (2) with an accuracy of 0.02 lbf/in (2).
      The challenges in biocompatible packaging, transducer drift, power management,
      and in vivo signal transmission are also discussed. This research brings
      researchers a step closer to continuous, real-time systemic monitoring that will
      allow one to analyze the dynamic human physiology.

PMID- 19174357
TI  - Fabric-based active electrode design and fabrication for health monitoring
      clothing.
AB  - In this paper, two versions of fabric-based active electrodes are presented to
      provide a wearable solution for ECG monitoring clothing. The first version of
      active electrode involved direct attachment of surface-mountable components to a
      textile screen-printed circuit using polymer thick film techniques. The second
      version involved attaching a much smaller, thinner, and less obtrusive interposer
      containing the active electrode circuitry to a simplified textile circuit. These
      designs explored techniques for electronic textile interconnection, chip
      attachment to textiles, and packaging of circuits on textiles for durability. The
      results from ECG tests indicate that the performance of each active electrode is
      comparable to commercial Ag/AgCl electrodes. The interposer-based active
      electrodes survived a five-cycle washing test while maintaining good signal
      integrity.

PMID- 19174358
TI  - Characterizing the complexity of spontaneous electrical signals in cultured
      neuronal networks using approximate entropy.
AB  - In this paper, neurons were cultured on a substrate above a multielectrode array,
      so the changes of electrophysiological activity patterns during development of
      the neuronal network or in response to environmental perturbations were
      monitored. But the complexity of these spontaneous activity patterns is not well
      understood. In order to solve the problem, a comprehensive method (approximate
      entropy (ApEn) in combination with a "sliding window" over the data) is
      introduced to quantify the complexity of four spontaneous activity patterns
      (sporadic spikes, tonic spikes, pseudobursts, and typical bursts) in cultured
      hippocampal neuronal networks. The results show that the dynamic curves of ApEn
      illustrate vivid differences between the four patterns and the values of ApEn
      fall into different ranges. Among these patterns, the complexity of tonic spikes
      is the highest while that of pseudobursts is the lowest. This suggests that the
      proposed method is a valid procedure for tracking the dynamic variation in
      neuronal signals and can distinguish the different firing patterns of neuronal
      networks in terms of their complexity.

PMID- 19174359
TI  - Mobile technology and healthcare: the adoption issues and systemic problems.
AB  - Although the benefits that are associated with mobile technology have been
      recognised as offering great potential in the healthcare sector, its widespread
      adoption has been lagging. We propose that fundamental systemic issues are likely
      to be the main barriers to adoption. We explain that the fragmented nature of the
      conservative healthcare system, the contradictory incentives and improper outcome
      measures conspire to make the innovative adoption of mobile technology
      problematic. Researchers can only gain a limited understanding of a technology's
      potential success by using technology adoption frameworks and need to supplement
      this with a 'systems' perspective that takes a more strategic view.

PMID- 19174360
TI  - The internet and civil disobedience: examining a new form of e-health behaviour.
AB  - The use of the internet by healthcare consumers is growing at a phenomenal rate.
      It is now commonplace for consumers to make critical medical decisions using web
      based health information and use the internet for prescription drug purchases and
      communication within disease-specific internet support groups. A corresponding
      trend is unmistakable: there is a clear and identifiable 'civil disobedience' by
      healthcare consumers and a growing number of benefits managers who use the
      internet for illegal prescription drug purchases as interpreted by the US Food
      and Drug Administration (USFDA). This is seen not only in the lay public, but is
      being adopted by a growing army of government officials and policy-makers as
      well. This phenomenon carries important social and policy implications as the
      delivery of healthcare continues to defy national borders and policies.

PMID- 19174361
TI  - A survey on the use of technology to support hospice interdisciplinary team
      meetings.
AB  - Interdisciplinary teamwork is essential in the delivery of hospice services.
      Hospice agencies in the USA are required by law to follow an interdisciplinary
      approach to patient care. The goal of this study is to assess the current level
      of technology use in hospice Interdisciplinary Team (IDT) meetings and identify
      the areas where technology can be utilised to address the challenges or barriers
      that IDT meetings face. We conducted a semistructured phone survey using
      purposive sampling based on US hospice utilisation rates. The representatives of
      190 agencies participated. The findings indicate that technology is not widely
      used in team meetings. Less than half of the agencies report computer use during
      meetings. The respondents saw benefits in using technology to access patient
      records and medication lists and design the care plan. Technology can become a
      powerful tool if introduced to enhance the social and product function of a group
      process.

PMID- 19174362
TI  - Communicating e-health research across organisational boundaries: a medical model
      for temporary or limited communities of practice.
AB  - The growth of collaborative, cross-organisational medical research in recent
      years has seen extensive and impressive innovations in the use of supporting
      technologies. Greater collaboration, however, presents new communication
      challenges. Given the diverse and varied organisational structures involved,
      there exists the need for a common and neutral work area, in effect creating a
      Temporary Virtual Organisation (TVO), which respects the needs and restrictions
      of widely varied organisational structures without becoming dominated by any one
      entity. The key in the creation of a TVO is that a unique process of
      institutional review is required. Also, because information is drawn from a
      number of disparate and often incompatible information sources, a standardised
      communication and information flow is needed well before data is collected,
      transmitted and utilised by members. Review of an innovative cancer research TVO
      initiative demonstrates that Common Data Elements (CDEs) and enhanced metadata
      are key to such a process and are described here, along with critical planning
      lessons learned from a model genetic biomarker research consortium.

PMID- 19174363
TI  - Managing the quality of health information using electronic medical records: an
      exploratory study among clinical physicians.
AB  - As technology is advancing in the healthcare field, ways of reducing costs and
      improving quality are key initiatives in the tedious processes of operations
      planning. There are several ways of reducing costs and improving quality
      management. One such way is the implementation of Electronic Health Records
      (HERs). A personally interviewed sample from a relatively large healthcare
      facility located in Pittsburgh, Pennsylvania, which is associated with the
      University of Pittsburgh Medical Center, netted a total of 44 physicians. There
      were no statistically significant relationships found based on 'clinicians'
      willingness to accept Electronic Medical Record (EMR)-embedded systems with
      gender', 'benefits outweigh risks for EMR-embedded implementation', 'EMR-embedded
      systems should be mandated', 'EMR-embedded systems should be administered by the
      federal government', 'EMR-embedded systems should be administered by regional
      systems', 'EMR applications are an invasion of privacy' and 'IT-related
      technologies pose an added threat to the healthcare environment'. It was only for
      the independent variable 'improves quality of care by EMR-embedded
      implementation' that most physicians felt that such a technology does positively
      impact patient care.

PMID- 19174364
TI  - The impact of globalisation on teleradiology practice.
AB  - Some advocates of globalisation argue that a free market with little regulation
      is the best approach for achieving cost-effective healthcare. Healthcare,
      however, is different from other business activities in that it is typically less
      profit-driven; instead, it often involves the goal of providing equitable care to
      the underprivileged. Traditionally, the government has subsidised the expenses of
      delivering affordable healthcare to underserved communities. Because of the many
      recent advances in telecommunications technology, telemedicine has gained
      increasing attention. Teleradiology, in particular, is by far the maturest of all
      telemedicine disciplines and, thus, it may serve as a pivotal indicator of
      whether telemedicine on a global scale is feasible or not. In this paper, a
      prediction of the future landscape of globalised teleradiology operations is
      attempted based on the extrapolation of the historical trends in teleradiology
      practice as well as the growing pressure on federal and local governments to
      reduce their regulatory power under the General Agreement on Trade in Services
      (GATS).

PMID- 19174365
TI  - Facilitating superior chronic disease management through a knowledge-based
      systems development model.
AB  - To date, the adoption and diffusion of technology-enabled solutions to deliver
      better healthcare has been slow. There are many reasons for this. One of the most
      significant is that the existing methodologies that are normally used in general
      for Information and Communications Technology (ICT) implementations tend to be
      less successful in a healthcare context. This paper describes a knowledge-based
      adaptive mapping to realisation methodology to traverse successfully from idea to
      realisation rapidly and without compromising rigour so that success ensues. It is
      discussed in connection with trying to implement superior ICT-enabled approaches
      to facilitate superior Chronic Disease Management (CDM).

PMID- 19174366
TI  - Safeguarding patient privacy in electronic healthcare in the USA: the legal view.
AB  - The conflict between the sweeping power of technology to access and assemble
      personal information and the ongoing concern about our privacy and security is
      ever increasing. While we gradually need higher electronic access to medical
      information, issues relating to patient privacy and reducing vulnerability to
      security breaches surmount. In this paper, we take a legal perspective and
      examine the existing patchwork of laws and obligations governing health
      information in the USA. The study finds that as Electronic Medical Records (EMRs)
      increase in scope and dissemination, privacy protections gradually decrease due
      to the shortcomings in the legal system. The contributions of this paper are (1)
      an overview of the legal EMR issues in the USA, and (2) the identification of the
      unresolved legal issues and how these will escalate when health information is
      transmitted over wireless networks. More specifically, the paper discusses
      federal and state government regulations such as the Electronic Communications
      Privacy Act, the Health Insurance Portability and Accountability Act (HIPAA) and
      judicial intervention. Based on the legal overview, the unresolved challenges are
      identified and suggestions for future research are included.

PMID- 19174367
TI  - The use of websites for disseminating health information in developing countries:
      an experience from Sri Lanka.
AB  - This study was designed to investigate the use of websites as a health education
      medium in Sri Lanka. Approximately 87.2% of the websites contained less than 100
      webpages. The quality score was higher in the websites owned by local nonbusiness
      organisations compared to the websites owned by business organisations. Only 8.1%
      of the websites provided health education content for the general public as their
      main content. The total number of websites has not increased compared to the
      increase in internet usage in Sri Lanka during the last few years. The internet
      is an underutilised health education tool despite the growth of internet usage in
      Sri Lanka.

PMID- 19174368
TI  - Static magnetotherapy for the treatment of insomnia.
AB  - Magnets have been used for centuries to treat a number of physical disorders. The
      vast majority of research, however, on static magnet therapy for insomnia has
      been confined to the auricular type of therapy, with publications limited to
      Chinese journals. Most of these studies have depended on the subjective self
      assessment of participants rather than objective scientific measurements. In this
      study, the authors report the positive preliminary results of insomnia treatment
      using pillows with embedded magnets, magnetic insoles and TriPhase bracelets. The
      analysis is based on objective actigraphic and polysomnographic data. A theory of
      accelerated transition from wakefulness to sleep is proposed to explain the
      process of insomnia relief through low-strength static magnetic fields. Analysis
      by functional Magnetic Resonance Imaging (fMRI) is used to further investigate
      the theory.

PMID- 19174369
TI  - Activation of farnesoid X receptor prevents atherosclerotic lesion formation in
      LDLR-/- and apoE-/- mice.
AB  - The role of farnesoid X receptor (FXR) in the development of atherosclerosis has
      been unclear. Here, LDL receptor (LDLR(-/-)) or apolipoprotein E (apoE(-/-))
      female or male mice were fed a Western diet and treated with a potent synthetic
      FXR agonist, WAY-362450. Activation of FXR blocked diet-induced
      hypertriglyceridemia and elevations of non-HDL cholesterol and produced a near
      complete inhibition of aortic lesion formation. WAY-362450 also induced small
      heterodimer partner (SHP) expression and repressed cholesterol 7alpha-hydroxylase
      (CYP7A1) and sterol 12 alpha-hydroxylase (CYP8B1) expression. To determine if SHP
      was essential for these protective activities, LDLR(-/-)SHP(-/-) and apoE(-/
      )SHP(-/-) mice were similarly treated with WAY-362450. Surprisingly, a notable
      sex difference was observed in these mice. In male LDLR(-/-)SHP(-/-) or apoE(-/
      )SHP(-/-) mice, WAY-362450 still repressed CYP7A1 and CYP8B1 expression by 10
      fold and still strongly reduced non-HDL cholesterol levels and aortic lesion
      area. In contrast, in the female LDLR(-/-)SHP(-/-) or apoE(-/-)SHP(-/-) mice, WAY
      362450 only slightly repressed CYP7A1 and CYP8B1 expression and did not reduce
      non-HDL cholesterol or aortic lesion size. WAY-362450 inhibition of
      hypertriglyceridemia remained intact in LDLR(-/-) or apoE(-/-) mice lacking SHP
      of both sexes. These results suggest that activation of FXR protects against
      atherosclerosis in the mouse, and this protective effect correlates with
      repression of bile acid synthetic genes, with mechanistic differences between
      male and female mice.

PMID- 19174370
TI  - Abnormal functional specialization within medial prefrontal cortex in high
      functioning autism: a multi-voxel similarity analysis.
AB  - Multi-voxel pattern analyses have proved successful in 'decoding' mental states
      from fMRI data, but have not been used to examine brain differences associated
      with atypical populations. We investigated a group of 16 (14 males) high
      functioning participants with autism spectrum disorder (ASD) and 16 non-autistic
      control participants (12 males) performing two tasks (spatial/verbal) previously
      shown to activate medial rostral prefrontal cortex (mrPFC). Each task
      manipulated: (i) attention towards perceptual versus self-generated information
      and (ii) reflection on another person's mental state ('mentalizing'versus 'non
      mentalizing') in a 2 x 2 design. Behavioral performance and group-level fMRI
      results were similar between groups. However, multi-voxel similarity analyses
      revealed strong differences. In control participants, the spatial distribution of
      activity generalized significantly between task contexts (spatial/verbal) when
      examining the same function (attention/mentalizing) but not when comparing
      different functions. This pattern was disrupted in the ASD group, indicating
      abnormal functional specialization within mrPFC, and demonstrating the
      applicability of multi-voxel pattern analysis to investigations of atypical
      populations.

PMID- 19174371
TI  - Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is the most common hereditary subcortical vascular
      dementia. It is caused by mutations in NOTCH3 gene, which encodes a large
      transmembrane receptor Notch3. The key pathological finding is the accumulation
      of granular osmiophilic material (GOM), which contains extracellular domains of
      Notch3, on degenerating vascular smooth muscle cells (VSMCs). GOM has been
      considered specifically diagnostic for CADASIL, but the reports on the
      sensitivity of detecting GOM in patients' skin biopsy have been contradictory. To
      solve this contradiction, we performed a retrospective investigation of 131
      Finnish, Swedish and French CADASIL patients, who had been adequately examined
      for both NOTCH3 mutation and presence of GOM. The patients were examined
      according to the diagnostic practice in each country. NOTCH3 mutations were
      assessed by restriction enzyme analysis of specific mutations or by sequence
      analysis. Presence of GOM was examined by electron microscopy (EM) in skin
      biopsies. Biopsies of 26 mutation-negative relatives from CADASIL families served
      as the controls. GOM was detected in all 131 mutation positive patients.
      Altogether our patients had 34 different pathogenic mutations which included
      three novel point mutations (p.Cys67Ser, p.Cys251Tyr and p.Tyr1069Cys) and a
      novel duplication (p.Glu434_Leu436dup). The detection of GOM by EM in skin
      biopsies was a highly reliable diagnostic method: in this cohort the congruence
      between NOTCH3 mutations and presence of GOM was 100%. However, due to the
      retrospective nature of this study, exact figure for sensitivity cannot be
      determined, but it would require a prospective study to exclude possible
      selection bias. The identification of a pathogenic NOTCH3 mutation is an
      indisputable evidence for CADASIL, but demonstration of GOM provides a cost
      effective guide for estimating how far one should proceed with the extensive
      search for a new or an uncommon mutations among the presently known over 170
      different NOTCH3 gene defects. The diagnostic skin biopsy should include the
      border zone between deep dermis and upper subcutis, where small arterial vessels
      of correct size are located. Detection of GOM requires technically adequate
      biopsies and distinction of true GOM from fallacious deposits. If GOM is not
      found in the first vessel or biopsy, other vessels or additional biopsies should
      be examined.

PMID- 19174372
TI  - Effect of brain magnetic resonance imaging on body core temperature in sedated
      infants and children.
AB  - BACKGROUND: Children undergoing magnetic resonance imaging (MRI) under sedation
      are at risk of hypo- or hyperthermia. The effect of brain MRI at differing
      magnetic field strengths on body core temperature in sedated infants and young
      children has not been reported previously. METHODS: Two groups of 38 infants and
      children (aged 1 month to 6 yr 5 months) underwent brain MRI for different
      indications related to cerebral diseases, at 1.5 Tesla (T) and 3 T MRI units,
      respectively. All patients received deep sedation comprising midazolam,
      nalbuphine, and propofol. Pre-scan and post-scan temperatures were measured at
      the right tympanic and at rectal sites. No active warming devices were used
      during the procedures. RESULTS: Body core temperature measurements were similar
      between right tympanic and rectal site before and after the scans. After 1.5 T
      scans, the median (IQR) increase from pre-scan to post-scan tympanic temperature
      was 0.2 degrees C (0.1-0.3), and the median (IQR) rectal temperature increase was
      0.2 degrees C (0-0.3) (P<0.001). After 3 T scans, the median (IQR) tympanic
      temperature increase was 0.5 degrees C (0.4-0.7), and the median (IQR) rectal
      temperature increase was 0.5 degrees C (0.3-0.6) (P<0.001). CONCLUSIONS: Body
      core temperature increased significantly during 1.5 and 3 T examinations; this
      increase was more profound during 3 T MRI. Patient heating occurred despite
      minimal efforts to reduce passive heat loss under sedation and without the use of
      warming devices.

PMID- 19174373
TI  - Ultrasound guidance compared with electrical neurostimulation for peripheral
      nerve block: a systematic review and meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Despite the growing interest in the use of ultrasound (US) imaging to
      guide performance of regional anaesthetic procedures such as peripheral nerve
      blocks, controversy still exists as to whether US is superior to previously
      developed nerve localization techniques such as the use of a peripheral nerve
      stimulator (PNS). We sought to clarify this issue by performing a systematic
      review and meta-analysis of all randomized controlled trials that have compared
      these two methods of nerve localization. METHODS: We searched Ovid MEDLINE, the
      Cochrane Central Register of Controlled Trials, and Google Scholar databases and
      also the reference lists of relevant publications for eligible studies. A total
      of 13 studies met our criteria and were included for analysis. Studies were rated
      for methodological quality by two reviewers. Data from these studies were
      abstracted and synthesized using a meta-analysis. RESULTS: Blocks performed using
      US guidance were more likely to be successful [risk ratio (RR) for block failure
      0.41, 95% confidence interval (CI) 0.26-0.66, P<0.001], took less time to perform
      (mean 1 min less to perform with US, 95% CI 0.4-1.7 min, P=0.003), had faster
      onset (29% shorter onset time, 95% CI 45-12%, P=0.001), and had longer duration
      (mean difference 25% longer, 95% CI 12-38%, P<0.001) than those performed with
      PNS guidance. US guidance also decreased the risk of vascular puncture during
      block performance (RR 0.16, 95% CI 0.05-0.47, P=0.001). CONCLUSIONS: US improves
      efficacy of peripheral nerve block compared with techniques that utilize PNS for
      nerve localization. Larger studies are needed to determine whether or not the use
      of US can decrease the number of complications such as nerve injury or systemic
      local anaesthetic toxicity.

PMID- 19174374
TI  - Safety and efficacy of cryoablation of atrial tachycardia with high risk of
      ablation-related injuries.
AB  - AIMS: The purpose of this study was to evaluate the safety and efficacy of
      cryoablation as an alternative to radio frequency (RF) ablation in high-risk
      located atrial tachycardia (AT). METHODS AND RESULTS: Between 2004 and 2007, 164
      patients underwent catheter ablation due to AT at our institution. Twenty-six of
      these patients (22 women and 4 men), median age 58 years (range 14-76), were
      considered having high-risk-located AT and were treated by cryoablation. Seven
      patients had failed prior RF ablation due to high risk of complications. The AT
      foci distribution was: close to the AV node (n = 14), vicinity of the sinus node
      (n = 7), and crista terminalis adjacent to the phrenic nerve (n = 5).
      Cryomapping, using a 6 mm tip catheter, at -30 degrees C was performed before
      ablation with a goal temperature of -80 degrees C for 240 s. Acute success rate
      was achieved in 25/26 patients (96%). During a follow-up of 493 +/- 258 days,
      three patients had recurrences. Two of these underwent a second successful
      cryoablation procedure. Long-term success rate was 92%. Phrenic nerve palsy
      occurred in two patients with complete recovery after 1 day and 5 months,
      respectively. CONCLUSION: Cryoablation of high-risk-located AT foci is a safe and
      effective alternative to RF therapy.

PMID- 19174375
TI  - Twiddling in cardiac resynchronization therapy: 'when length matters'.
AB  - We report on a 75-year-old woman who successfully underwent cardiac
      resynchronization therapy. Two weeks after implantation, right continuous
      pectoral stimulation appeared. Retraction and dislodgement of the right atrial
      and right ventricular leads as well as coiling of the three leads around the
      device generator were observed on chest radiography, but, surprisingly, the left
      ventricular lead remained unaffected due to its major length to facilitate the
      manoeuvers of implantation.

PMID- 19174376
TI  - Accuracy of manual QRS duration assessment: its importance in patient selection
      for cardiac resynchronization and implantable cardioverter defibrillator therapy.
AB  - AIMS: Patients with left ventricular systolic dysfunction and
      electrocardiographic QRS duration (QRSd) >or=120 ms may obtain symptomatic and
      prognostic benefits from cardiac resynchronization therapy (CRT). However,
      clinical trials do not describe the methods used to measure QRSd. We investigated
      the effect of electrocardiogram (ECG) display format and paper speed on the
      accuracy of manual QRSd assessment and concordance of manual QRSd with computer
      calculated mean and maximal QRSd. METHODS AND RESULTS: Six cardiologists
      undertook QRSd measurements on ECGs, with computer-calculated mean QRSd close to
      120 ms. Display formats were 12-lead, 6-limb, and 6-precordial leads, each at 25
      and 50 mm/s. When the computer-calculated mean was used to define QRSd, manual
      assessment demonstrated 97 and 83% concordance at categorizing QRSd as < and
      >or=120 ms, respectively. Using the computer-calculated maximal QRSd, manual
      assessment demonstrated 83% concordance when QRSd was <120 ms and 19% concordance
      when QRSd was >or=120 ms. The six-precordial lead format demonstrated
      significantly less intra and inter-observer variabilities than the 12-lead, but
      this did not improve concordance rates. CONCLUSION: Manual QRSd assessments
      demonstrate significant variability, and concordance with computer-calculated
      measurement depends on whether QRSd is defined as the mean or maximal value.
      Consensus is required both on the most appropriate definition of QRSd and its
      measurement.

PMID- 19174377
TI  - Radiologically identified fracture of an implantable cardioverter defibrillator
      lead: fact or fiction?

PMID- 19174378
TI  - A preliminary assessment of the effects of ATI-2042 in subjects with paroxysmal
      atrial fibrillation using implanted pacemaker methodology.
AB  - AIMS: ATI-2042 (budiodarone) is a chemical analogue of amiodarone with a half
      life of 7 h. It is electrophysiologically similar to amiodarone, but may not have
      metabolic and interaction side effects. The sophisticated electrocardiograph logs
      of advanced DDDRP pacemakers were used to monitor the efficacy of ATI-2042. The
      aim of this study was to determine the preliminary efficacy and safety of ATI
      2042 in patients with paroxsymal atrial fibrillation (PAF) and pacemakers.
      METHODS AND RESULTS: Six women with AF burden (AFB) between 1 and 50% underwent
      six sequential 2-week study periods. Patients received 200 mg bid of ATI-2042
      during Period 2 (p2), 400 mg bid during p3, 600 mg bid during p4, 800 mg bid
      during p5, and no drug during baseline and washout (p1 and p6). Pacemaker data
      for the primary outcome measure AFB were downloaded during each period. Mean AFB
      decreased between baseline and all doses: AFB at baseline (SD) was 20.3 +/- 14.6%
      and mean AFB at 200 mg bid was 5.2 +/- 4.2%, at 400 mg bid 5.2 +/- 5.2%, at 600
      mg bid 2.8 +/- 3.4%, and at 800 mg bid 1.5 +/- 0.5%. The mean reductions in AFB
      at all doses of ATI-2042 were statistically significant (P < 0.005). Atrial
      fibrillation burden increased in washout. Atrial fibrillation episodes tended to
      increase with ATI-2042, but this was offset by substantial decreases in episode
      duration. ATI-2042 was generally well tolerated. CONCLUSION: ATI-2042 effectively
      reduced AFB over all doses studied by reducing mean episode duration. A large
      scale study will be required to confirm this effect.

PMID- 19174380
TI  - Monte Carlo dosimetry for targeted irradiation of individual cells using a
      microbeam facility.
AB  - Microbeam facilities provide a unique opportunity to investigate the effects of
      ionising radiation on living biological cells with a precise control of the
      delivered dose. This paper describes dosimetry calculations performed at the
      single-cell level in the microbeam irradiation facility available at the Centre
      d'Etudes Nucleaires de Bordeaux-Gradignan in France, using the object-oriented
      Geant4 Monte Carlo simulation toolkit. The cell geometry model is based on high
      resolution three-dimensional voxelised phantoms of a human keratinocyte (HaCaT)
      cell line. Such phantoms are built from confocal microscopy imaging and from ion
      beam chemical elemental analysis. Results are presented for single-cell
      irradiation with 3 MeV incident alpha particles.

PMID- 19174379
TI  - Population genetic structure of two Medicago species shaped by distinct life
      form, mating system and seed dispersal.
AB  - BACKGROUND AND AIMS: Life form, mating system and seed dispersal are important
      adaptive traits of plants. In the first effort to characterize in detail the
      population genetic structure and dynamics of wild Medicago species in China, a
      population genetic study of two closely related Medicago species, M. lupulina and
      M. ruthenica, that are distinct in these traits, are reported. These species are
      valuable germplasm resources for the improvement of Medicago forage crops but are
      under threat of habitat destruction. METHODS: Three hundred and twenty-eight
      individuals from 16 populations of the annual species, M. lupulina, and 447
      individuals from 15 populations of the perennial species, M. ruthenica, were
      studied using 15 and 17 microsatellite loci, respectively. Conventional and
      Bayesian-clustering analyses were utilized to estimate population genetic
      structure, mating system and gene flow. KEY RESULTS: Genetic diversity of M.
      lupulina (mean H(E)=0.246) was lower than that of M. ruthenica (mean H(E)=0.677).
      Populations of M. lupulina were more highly differentiated (F(ST)=0.535) than
      those of M. ruthenica (F(ST)=0.130). For M. lupulina, 55.5% of the genetic
      variation was partitioned among populations, whereas 76.6% of the variation
      existed within populations of M. ruthenica. Based on the genetic data, the
      selfing rates of M. lupulina and M. ruthenica were estimated at 95.8% and 29.5%,
      respectively. The genetic differentiation among populations of both species was
      positively correlated with geographical distance. CONCLUSIONS: The mating system
      differentiation estimated from the genetic data is consistent with floral
      morphology and observed pollinator visitation. There was a much higher historical
      gene flow in M. ruthenica than in M. lupulina, despite more effective seed
      dispersal mechanisms in M. lupulina. The population genetic structure and
      geographical distribution of the two Medicago species have been shaped by life
      form, mating systems and seed dispersal mechanisms.

PMID- 19174381
TI  - Building organizational capacity: a cornerstone of health system reform.
AB  - The U.S. health care delivery system is in need of overhaul. Care is fragmented,
      unsafe, and inefficient. Achieving higher levels of performance requires
      organizational capacity, including information technology (IT) and specialized
      expertise, not present in most settings. Organizational capacity is fortified
      through the benefits of larger scale and clinical integration. The evolution of
      new organizational structures will open up opportunities to redesign payment
      programs and invest capital toward building high-performing systems. A
      comprehensive policy agenda is needed to encourage growth in organizational
      capacity, including national priorities and goals, performance measurement and
      reporting, payment reform, community leadership, IT, and public education.

PMID- 19174382
TI  - Payment reform alone will not transform health care delivery.
AB  - Payment reforms clearly are an important change agent in our efforts to improve
      the health care delivery system. For broader health care delivery reform to take
      root and work, however, payment reform cannot be imposed in a vacuum. To maximize
      the chances of success and minimize the possibility of unintended consequences,
      the appropriate culture and structure of our health care institutions first must
      be in place.

PMID- 19174383
TI  - Fostering accountable health care: moving forward in medicare.
AB  - To succeed, health care reform must slow spending growth while improving quality.
      We propose a new approach to help achieve more integrated and efficient care by
      fostering local organizational accountability for quality and costs through
      performance measurement and "shared savings" payment reform. The approach is
      practical and feasible: it is voluntary for providers, builds on current referral
      patterns, requires no change in benefits or lock-in for beneficiaries, and offers
      the possibility of sustained provider incomes even as total costs are
      constrained. We simulate the potential expenditure impact and show that
      significant Medicare savings are possible.

PMID- 19174384
TI  - Medicare: the place to start delivery system reform.
AB  - The development of accountable care organizations (ACOs) is an appropriate goal
      for delivery system reform. The Medicare program can be instrumental in starting
      the necessary transformations in payment design, incentives, and delivery system
      structure. Payment reforms are critical; should come first; and may need to be
      substantial, cumulative in impact, and dramatic in design. Learning from
      successful models of physician-hospital integration and creating new models that
      can pass legal, regulatory, and antitrust concerns will be needed, if the promise
      of ACOs is to be fulfilled.

PMID- 19174385
TI  - A consumer perspective on physician payment reform.
AB  - Changing the incentives to providers through payment policy is a critical step
      toward realizing our goals for excellent health care performance. As a part of
      the needed transformation, both providers and consumers will need to be mindful
      of resources and of the fact that more services do not always lead to better
      health. Without serious efforts to promote engagement by patients and caregivers,
      however, the goals of payment reform could be defeated. Patients can be partners
      in achieving greater efficiency and effectiveness with aggressive decision
      support based on best practices. We cannot put physicians' incomes and patients'
      well-being on a collision course.

PMID- 19174386
TI  - Using Medicare payment policy to transform the health system: a framework for
      improving performance.
AB  - As the largest payer for health services in the United States, Medicare has the
      potential to use its payment policies to stimulate change in the organization of
      care to improve quality and mitigate cost growth. This paper proposes a framework
      in which Medicare would offer an array of new bundled payment options for
      physician group practices, hospitals, and delivery systems, with incentives to
      encourage greater integration in the organization of health care delivery and the
      provision of more coordinated care to beneficiaries. These changes could also
      serve as a model for other payers to improve quality and efficiency throughout
      the health system.

PMID- 19174387
TI  - Measuring outcomes and efficiency in medicare value-based purchasing.
AB  - The Medicare program may soon adopt value-based purchasing (VBP), in which
      hospitals could receive incentives that are conditional on meeting specified
      performance objectives. The authors advocate for a market-oriented framework and
      direct measures of system-level value that are focused on better outcomes and
      lower total cost of care. They present a multidimensional framework for measuring
      outcomes of care and a method to adjust incentive payments based on efficiency.
      Incremental reforms based on VBP could provoke transformational changes in total
      patient care by linking payments to value related to the whole patient
      experience, recognizing shared accountability among providers.

PMID- 19174388
TI  - Payment reform options: episode payment is a good place to start.
AB  - New strategies to control U.S. health spending growth are urgently needed.
      Although provider payment cuts are likely, cutting fee-for-service (FFS) payments
      will hurt quality and access. A more sensible approach would be to restructure
      the delivery system into organized networks of providers delivering reliable,
      evidence-based care. But restructuring will not occur without payment policy
      reform. Four policy options are commonly cited: recalibrating FFS, instituting
      pay-for-performance, creating episode-based payments, and adopting global
      payments. We argue that episode payments are the most immediately viable
      approach, and we recommend that payment reforms precede any payment reductions so
      that new delivery models can gain traction.

PMID- 19174389
TI  - Consumer-driven health care: promise and performance.
AB  - This paper analyzes the evolution of consumer-driven health care in terms of its
      original vision, its subsequent implementation, and the transformations it has
      endured as it moves into its second decade. The market is generating product
      designs that combine elements of consumerism with elements of managed care, but
      the trend is always toward a stronger role for consumer choice and a weaker role
      for management of those choices by physicians, insurers, employers, and
      regulators.

PMID- 19174390
TI  - Costs and benefits of health information technology: new trends from the
      literature.
AB  - To understand what is new in health information technology (IT), we updated a
      systematic review of health IT with studies published during 2004-2007. From
      4,683 titles, 179 met inclusion criteria. We identified a proliferation of
      patient-focused applications although little formal evaluation in this area; more
      descriptions of commercial electronic health records (EHRs) and health IT systems
      designed to run independently from EHRs; and proportionately fewer relevant
      studies from the health IT leaders. Accelerating the adoption of health IT will
      require greater public-private partnerships, new policies to address the
      misalignment of financial incentives, and a more robust evidence base regarding
      IT implementation.

PMID- 19174391
TI  - Measuring, monitoring, and managing quality in Germany's hospitals.
AB  - In German hospitals, quality measurement, monitoring, and management have
      undergone considerable development. This includes an array of mandatory measures,
      including a nationwide benchmarking exercise based on 194 indicators. Because of
      better and deeper coding of diagnoses, procedures, and demographic information
      since the introduction of the diagnosis-related group (DRG) system, two further
      "generations" of instruments have been developed: quality measurement performed
      at the provider (hospital) level using administrative data, and long-term
      performance measurement using administrative data at the payer level. All three
      approaches have specific pros and cons concerning validity regarding final
      outcomes and resistance against manipulation.

PMID- 19174393
TI  - Measuring the performance of an inter-hospital transport service.

PMID- 19174392
TI  - Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta
      analysis of observational studies.
AB  - OBJECTIVES: To assess whether smoking is a risk factor for developing rheumatoid
      arthritis (RA). DESIGN: Meta-analysis. METHOD:  DATA SOURCES: were observational
      studies that examined the association between smoking history and the risk of
      developing RA identified through Medline and EMBASE (from 1966 to December 2006),
      relevant books and a reference search. Two authors independently extracted the
      following: authors' names, publication year, sample size, participant
      characteristics, odds ratios (OR) or relative risks, adjustment factors, study
      design and area where the study was conducted. Data syntheses were based upon
      random effects model. Summarised syntheses effects were expressed by OR. RESULTS:
      Sixteen studies were selected from among 433 articles. For men, summary OR for
      ever, current and past smokers were 1.89 (95% CI 1.56 to 2.28), 1.87 (1.49 to
      2.34) and 1.76 (1.33 to 2.31), respectively. For rheumatoid factor-positive (RF+)
      RA, summary OR for ever, current and past smokers were 3.02 (2.35 to 3.88), 3.91
      (2.78 to 5.50) and 2.46 (1.74 to 3.47), respectively. Summary OR for 20 or more
      pack-years of smoking was 2.31 (1.55 to 3.41). For women, summary OR for ever,
      current and past smokers were 1.27 (1.12 to 1.44), 1.31 (1.12 to 1.54) and 1.22
      (1.06 to 1.40), respectively. For RF+ RA, summary OR for ever, current and past
      smokers were 1.34 (0.99 to 1.80), 1.29 (0.94 to 1.77) and 1.21 (0.83 to 1.77).
      Summary OR for 20 or more pack-years of smoking was 1.75 (1.52 to 2.02).
      CONCLUSION: Smoking is a risk factor for RA, especially RF+ RA men and heavy
      smokers.

PMID- 19174394
TI  - Trachoma in the Pacific Islands: evidence from Trachoma Rapid Assessment.
AB  - AIMS: To establish the presence or absence of trachoma in the Pacific Island
      region. METHODS: Trachoma Rapid Assessment methodology was used in Kiribati,
      Nauru, Vanuatu, Solomon Islands and Fiji. Advised by key informants, high-risk
      communities were chosen from each country. All available children aged 1-9 years
      and adults > or = 40 years were examined. RESULTS: A total of 903 adults > or =
      40 years and 3102 children aged 1-9 years were screened at 67 sites. Rates of
      active trachoma in children were >15% in all sites in Kiribati and >20% in all
      sites in Nauru. However, there was a high variability of rates of active trachoma
      in survey sites in Vanuatu, Solomon Islands and Fiji with rates ranging from 0%
      to 43% (average 23.3%), 6.0% to 51.9% (average 30.5%) and 0% to 48.8% (average
      22.1%) respectively. Average rates of scarring trachoma in adults were 61.9% in
      Kiribati, 12.5% in Nauru, 38.2% in Vanuatu, 67.0% in the Solomon Islands and
      18.8% in Fiji. Rates of trichiasis and trichiasis surgeries suggest the
      possibility of blinding trachoma in the region. CONCLUSION: The findings indicate
      that trachoma is present in all the Pacific Island countries screened. Further
      prevalence studies are required, and trachoma control measures should be
      considered.

PMID- 19174395
TI  - Complications and 2-year valve survival following Ahmed valve implantation during
      the first 2 years of life.
AB  - AIM: To report complications and 2-year valve survival following Ahmed valve
      implantation during the first 2 years of life. METHODS: Retrospective
      institutional case series. RESULTS: Forty-two eyes of 36 patients with Ahmed
      valve implantation (without prior drainage device surgery) during the first 2
      years of life and 2 years' postsurgical follow-up were identified. Most eyes had
      primary congenital glaucoma (28/42, 66.7%), aphakic glaucoma (5/42, 11.9%) or
      Peters anomaly (5/42, 11.9%). All but three eyes had prior ocular surgery.
      Surgery was at a mean age of 11.83 months (m) (SD 5.63). The most common
      significant postoperative complications were tube malpositioning requiring
      intervention (11/42, 26.2%), endophthalmitis (3/42, 7.1%; one with tube exposure)
      and retinal detachment (3/42, 7.1%). Thirty-six eyes (85.8%) required resumption
      of antiglaucoma medications to maintain intraocular pressure (IOP) < or =22 mm Hg
      a mean of 7.2 m (SD 6.8) postoperatively. Cumulative probabilities of valve
      survival (IOP< or =22 mm Hg with or without medication) by Kaplan-Meier analysis
      were 73.8% and 63.3% at 12 months and 24 months, respectively. CONCLUSIONS:
      Postoperative tube malpositioning that required surgical revision was common in
      this age group. Infectious endophthalmitis and retinal detachment are known
      potential complications following any incisional surgery for advanced
      buphthalmos; however, tube exposure is a unique potential problem following
      aqueous shunt implantation that can lead to intraocular infection. Cumulative
      valve survival 2 years following implantation was 63.3%.

PMID- 19174397
TI  - Vascular endothelial growth factor Trap-Eye for diabetic macular oedema.

PMID- 19174398
TI  - Lord Shiva's third eye.

PMID- 19174399
TI  - Tuberculous dacryoadenitis in a Scottish teenager.

PMID- 19174400
TI  - An exploratory study of the safety, tolerability and bioactivity of a single
      intravitreal injection of vascular endothelial growth factor Trap-Eye in patients
      with diabetic macular oedema.
AB  - AIM: The aim of the study was to assess the safety and bioactivity of a single
      intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye in
      subjects with diabetic macular oedema (DMO). METHODS: Five subjects with DMO,
      foveal thickness > or =250 microm measured by optical coherence tomography (OCT),
      and best-corrected visual acuity (BCVA) between 20/40 and 20/320, were enrolled.
      Each participant received a single intravitreal injection of 4.0 mg of VEGF Trap
      Eye followed by a 6-week observation period. Outcome measures included safety and
      biological activity, including changes in BCVA and excess retinal thickness
      assessed by OCT. RESULTS: Injections of VEGF Trap-Eye were well tolerated with no
      ocular toxicity. One patient had an unrelated serious adverse event:
      hospitalisation for cellulitis of the left foot 27 days after injection of VEGF
      Trap-Eye. Median baseline BCVA was 36 ETDRS letters read at 4 m (not ETDRS visual
      acuity score; Snellen equivalent: 20/50) and median baseline excess central 1 mm
      foveal thickness (FTH) was 108 microm. At 4 weeks after injection, the median
      excess FTH was 59 microm and the median improvement in BCVA was nine letters. At
      6 weeks after injection, four of the five patients showed improvement in excess
      FTH (median 74 microm; 31% reduction from baseline, p = 0.0625) and four of the
      five showed improvement in BCVA (median improvement of three letters).
      CONCLUSIONS: A single intravitreal injection of 4.0 mg of VEGF Trap-Eye was well
      tolerated and preliminary evidence of bioactivity was detected. These findings
      support additional studies investigating multiple injections of VEGF Trap-Eye in
      patients with DMO.

PMID- 19174401
TI  - HIV-1-mediated delivery of a short hairpin RNA targeting vascular endothelial
      growth factor in human retinal pigment epithelium cells.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) has been shown to play a
      major role in the pathological neovascularisation that occurs in degenerative
      retinal diseases like age-related macular degeneration (AMD). Although several
      approaches to attenuate VEGF show significant promise, repeated treatments are
      required to achieve therapeutic benefits. As lentiviruses efficiently and stably
      infect resting cells, a human immunodeficiency virus type 1 (HIV-1)-based vector
      was used for the delivery and long-term endogenous expression of a short hairpin
      RNA (shRNA) specific for VEGF in postmitotic human retinal pigment epithelium
      (RPE) cells. METHODS: An HIV-1 vector expressing a shRNA targeting VEGF was
      developed and adopted to transduce RPE cell cultures, in both normoxic and
      hypoxic conditions in vitro. Intracellular VEGF expression was analysed by
      western blotting, and the release of VEGF in culture supernatants was determined
      by ELISA. RESULTS: At least 90% of RPE cells were successfully transduced by HIV
      1 virions. Inhibition of VEGF expression and reduction by 95% of VEGF release in
      transduced cells were achieved. Moreover, shRNA-VEGF effectively and specifically
      prevented hypoxia-induced VEGF upregulation. CONCLUSION: HIV-1-mediated delivery
      of a shRNA-VEGF leading to gene expression knockdown could represent a novel
      therapeutic strategy against neovascularisation-related eye diseases.

PMID- 19174402
TI  - Analysis of soluble vascular endothelial growth factor receptor-1 secreted from
      cultured corneal and oral mucosal epithelial cell sheets in vitro.
AB  - BACKGROUND: In clinical trials, eyes transplanted with cultured oral mucosal
      epithelial cell sheets have shown increased neovascularisation compared with eyes
      treated with cultured corneal epithelial cell sheets. As reported recently,
      soluble vascular endothelial growth factor receptor-1 (soluble VEGFr-1) is a main
      factor to maintain a corneal avascularity. AIM: To investigate soluble VEGFr-1 of
      cultured corneal epithelial cells (CCE) and cultured oral mucosal epithelial
      cells (COE) in vitro. METHODS: Rabbit corneal and oral mucosal epithelial cells
      were co-cultured with mitomycin C-treated NIH/3T3 cells on culture plates. After
      CCE and COE were multilayered, culture medium was replaced by basal medium and
      incubated. Protein secretion of soluble VEGFr-1 was assessed in conditioned
      medium from CCE and COE by ELISA. Angiogenic potential was examined by invasion,
      migration assays with human umbilical vein endothelial cells (HUVECs) in addition
      to recombinant soluble VEGFr-1. RESULTS: CCE secreted a significantly higher
      amount of soluble VEGFr-1 than did COE. Recombinant soluble VEGFr-1 significantly
      suppressed HUVEC migration induced by COE, without suppression in CCE. In
      conclusion, these findings suggest that low protein levels of soluble VEGFr-1 may
      lead to corneal neovascularisation after COE sheet transplantation.

PMID- 19174403
TI  - Visualising vitreous through modified trans-scleral illumination by maximising
      the Tyndall effect.
AB  - BACKGROUND: A new technique for visualisation of the vitreous base is described.
      It uses a standard lightpipe for scleral indentation and transillumination.
      Visualisation of the vitreous using low light levels can be achieved by enhancing
      the Tyndall effect. DISCUSSION: Perfluorocarbon liquid (PFCL) is used to confine
      the aqueous environment to the anterior vitreous cavity and triamcinolone is
      added to increase light scatter. The technique clearly differentiates vitreous
      from PFCL and infusion fluid, and facilitates trimming of the vitreous base,
      draining of subretinal fluid and air/fluid exchange.

PMID- 19174405
TI  - A new view of the slit lamp.

PMID- 19174406
TI  - Piggyback intraocular lens implant to correct severe refractive error after
      penetrating keratoplasty in pseudophakes.

PMID- 19174407
TI  - Limits of the retinal-mapping program in age-related macular degeneration.

PMID- 19174408
TI  - Preoperative site marking.

PMID- 19174409
TI  - Awareness of eye tumours in Down syndrome.

PMID- 19174410
TI  - Effect of task familiarisation on distribution of energy during a 2000 m cycling
      time trial.
AB  - AIM: To investigate the effect of task familiarisation on the spontaneous pattern
      of energy expenditure during a series of 2000 m cycling time trials (TTs).
      METHOD: Nine trained males completed three 2000 m TTs on a Velotron cycling
      ergometer. To examine pacing strategy, the data were assigned to 250 m "bins,"
      with the pattern of aerobic and anaerobic energy expenditure calculated from
      total work accomplished and gas-exchange data. RESULTS: There were no significant
      differences between trials in performance times (191.4 (SD 4.3), 189.4 (4.6),
      190.1 (5.6) s), total aerobic (58.3 (2.7), 58.4 (3.1), 58.0 (3.4) kJ) and total
      anaerobic energy expenditure (16.4 (3.3), 17.3 (2.8), 16.5 (3.1) kJ). Pacing
      strategy in the second and third TT differed from the first TT in that a lower
      power output was adopted during the first 500 m, enabling a higher power output
      during the final 750 m of the TT. This adjustment in the pattern of energy
      expenditure was mediated by an alteration in the pattern of anaerobic energy
      expenditure, which paralleled changes in total energy expenditure. Furthermore,
      participants retained an anaerobic energy "reserve" enabling an end-spurt during
      the second and third trials. CONCLUSION: Small modifications to the pacing
      strategy are made following a single bout of exercise, primarily by altering the
      rate of anaerobic energy expenditure. This may have served to prevent critical
      metabolic disturbances. The alteration in pacing strategy following the first
      exercise bout is compatible with a complex intelligent regulatory system.

PMID- 19174411
TI  - A prospective cohort study of hamstring injuries in competitive sprinters:
      preseason muscle imbalance as a possible risk factor.
AB  - BACKGROUND: Hamstring injuries are common in sprinters. Identifying preseason
      risk factors is essential to target injury-prone athletes and develop injury
      preventive measures. OBJECTIVE: To investigate the incidence of hamstring muscle
      injury in sprinters over an athletic season and to explore the preseason
      predictor of this injury. DESIGN: Prospective cohort study. PARTICIPANTS: 44
      sprinters from the Hong Kong Sports Institute, the Hong Kong Amateur Athletic
      Association and intercollegiate athletic teams were recruited. METHODS: Preseason
      assessment of hamstring flexibility, concentric and eccentric isokinetic peak
      torque and peak torque angle were obtained at the beginning of an athletic
      season. The athletes were followed over 12 months and were asked to report all
      injuries resulting from training and competition. RESULTS: Eight athletes
      sustained hamstring injuries over the season. The injury rate was 0.87 per 1000 h
      of exposure. The incidence of injuries was higher at the beginning of the season,
      with 58.3% injuries occurring in the first 100 h of exposure. Cox regression
      analysis revealed that athletes with a decrease in the hamstring : quadriceps
      peak torque ratio of less than 0.60 at an angular velocity of 180 degrees/s have
      a 17-fold increased risk of hamstring injury. CONCLUSION: Performing preseason
      hamstring : quadriceps peak torque ratio assessments may be useful to identify
      sprinters susceptible to hamstring injury.

PMID- 19174412
TI  - Central aponeurosis tears of the rectus femoris: practical sonographic prognosis.
AB  - OBJECTIVE: This study is a statistical analysis to establish whether a
      correlation exists between the level and degree of rectus femoris (RF) central
      tendon injury and the amount of time that an athlete is unable to participate
      subsequently, referred to as "sports participation absence" (SPA). DESIGN: Causal
      comparative study. PATIENTS: 35 players from two high-level Spanish soccer teams
      with an injury to the central tendon of the RF based on clinical and ultrasound
      criteria. MAIN OUTCOME MEASURE: Ultrasound examination was performed with an 8-2
      MHz linear multifrequency transducer. All studies included both longitudinal and
      transverse RF sections. RESULTS: At the proximal level the SPA time is 45.1 days
      when the injury length is 4.0 cm. This value increases by 5.3 days with each 1 cm
      increase in the length of injury. In the case of distal level injury, SPA time is
      32.9 days when the injury length is 3.9 cm. This value increases by 3.4 days with
      each 1 cm increase. In the total representative sample, SPA time when the injury
      length is 4.2 cm corresponds to 39.1 days. This value increases by 4.2 days per
      length unit. CONCLUSIONS: RF central tendon injury at the proximal level is
      associated with a greater SPA time than at the distal level. Patients with a
      grade II injury have an SPA time longer than those with a grade I injury whether
      the injury is located proximal or distal.

PMID- 19174413
TI  - Permissive hypotension in the extremely low birthweight infant with signs of good
      perfusion.
AB  - INTRODUCTION: Many practitioners routinely treat infants whose mean arterial
      blood pressure in mm Hg is less than their gestational age in weeks (GA).
      OBJECTIVE: To assess the effectiveness of utilising a combined approach of
      clinical signs, metabolic acidosis and absolute blood pressure (BP) values when
      deciding to treat hypotension in the extremely low birthweight (ELBW) infant.
      METHODS: Retrospective cohort study of all live born ELBW infants admitted to our
      neonatal intensive care unit over a 4-year period. Patients were grouped as
      either normotensive (BP never less than GA), hypotensive and not treated (BP<GA
      but signs of good perfusion; we termed this permissive hypotension) and
      hypotensive treated (BP<GA with signs of poor perfusion). RESULTS: 118 patients
      were admitted during this period. Blood pressure data were available on 108
      patients. 53% of patients were hypotensive (mean BP in mm Hg less than GA in
      weeks). Treated patients had lower birth weight and GA, and significantly lower
      blood pressure at 6, 12, 18 and 24 h. Normotensive patients and patients
      designated as having permissive hypotension had similar outcomes. Mean blood
      pressure in the permissive group increased from 26 mm Hg at 6 h to 31 mm Hg at 24
      h. In a logistic regression model, treated hypotension is independently
      associated with mortality, odds ratio 8.0 (95% CI 2.3 to 28, p<0.001).
      CONCLUSIONS: Blood pressure spontaneously improves in ELBW infants during the
      first 24 h. Infants hypotensive on GA criteria but with clinical evidence of good
      perfusion had as good an outcome as normotensive patients. Treated low blood
      pressure was associated with adverse outcome.

PMID- 19174414
TI  - Management of neonatal abstinence syndrome: a national survey and review of
      practice.
AB  - AIM: To ascertain the present management of neonatal abstinence syndrome (NAS) in
      neonatal units in the United Kingdom (UK) and Ireland. METHODS: Postal
      questionnaire to 235 neonatal units, with telephone follow-up of non-respondents.
      RESULTS: The response rate was 90%, and 96% of respondents had a formal NAS
      guideline. The median number of infants treated annually for NAS was 6 (range 1
      100). The method of Finnegan was the most widely used scoring system (52%).
      Morphine sulphate was the most commonly used first line agent for both opiate
      (92%) and polysubstance (69%) withdrawal. Dosing regimens varied widely. Units
      using a maximum daily morphine dose of <400 microg/kg/day were more likely to
      require the addition of a second agent (76% vs 58%, p = 0.027). Phenobarbitone
      was the drug of choice to treat seizures secondary to both opiate and polydrug
      withdrawal in 73% and 81% of units, respectively. 29% of units allowed infants to
      be discharged home on medication. 58% of these allowed administration of opiates
      in the community and in almost half of cases this was managed by a parent.
      Mothers on methadone whose serology was positive for hepatitis B and/or C were
      four times more likely to be discouraged from breastfeeding. CONCLUSIONS: The
      majority of units currently use an opiate as the drug of first choice as
      recommended. Doses utilised and second agents added vary significantly between
      units. Many of our findings reflect the lack of high-quality randomised studies
      regarding management of NAS.

PMID- 19174415
TI  - Visceral fat accumulation is an independent risk factor for hepatocellular
      carcinoma recurrence after curative treatment in patients with suspected NASH.
AB  - BACKGROUND AND AIMS: Visceral fat accumulation reportedly increases the risk of
      hepatocellular carcinoma (HCC) development in patients with chronic liver
      disease. However, it has not been fully elucidated whether visceral fat
      accumulation increases the risk of HCC recurrence after curative treatment in
      patients with suspected non-alcoholic steatohepatitis (NASH). Therefore this was
      investigated in the current study. METHODS: 62 patients with naive HCC with
      suspected NASH were enrolled. All were curatively treated with percutaneous
      radiofrequency ablation between 1999 and 2006. The visceral fat area (VFA) was
      determined in each patient from CT images, taken at the time of HCC diagnosis.
      Patients were divided into two groups based on VFA: the high VFA group (>130
      cm(2) in males, >90 cm(2) in females, n = 27) and the others (n = 35). The
      effects of VFA on HCC recurrence were analysed together with other factors
      including patients' background, tumour-related factors and liver function-related
      factors. RESULTS: The cumulative recurrence rates differed significantly between
      the two groups; 15.9, 56.5 and 75.1% at 1, 2 and 3 years, respectively, in the
      high VFA group, and 9.7, 31.1 and 43.1%, respectively, in the controls (p =
      0.018). Multivariate analysis indicated visceral fat accumulation (risk ratio
      1.08, per 10 cm(2), p = 0.046) and older age (risk ratio 1.06 per 1 year, p =
      0.04) as independent risk factors of HCC recurrence. CONCLUSIONS: Visceral fat
      accumulation is an independent risk factor of HCC recurrence after curative
      treatment in patients with suspected NASH.

PMID- 19174416
TI  - Effect of binge drinking on the liver: an alarming public health issue?

PMID- 19174417
TI  - Toll-like receptor 2 is critical for induction of Reg3 beta expression and
      intestinal clearance of Yersinia pseudotuberculosis.
AB  - OBJECTIVE: Yersinia pseudotuberculosis causes ileitis and mesenteric
      lymphadenitis by mainly invading the Peyer's patches that are positioned in the
      terminal ileum. Whereas toll-like-receptor 2 (TLR2) controls mucosal inflammation
      by detecting certain microbiota-derived signals, its exact role in protecting
      Peyer's patches against bacterial invasion has not been defined. DESIGN: Wild
      type, Tlr2-, Nod2- and MyD88-deficient animals were challenged by Y
      pseudotuberculosis via the oral or systemic route. The role of microbiota in
      conditioning Peyer's patches against Yersinia through TLR2 was assessed by
      delivering, ad libitum, exogenous TLR2 agonists in drinking water to germ-free
      and streptomycin-treated animals. Bacterial eradication from Peyer's patches was
      measured by using a colony-forming unit assay. Expression of cryptdins and the c
      type lectin Reg3 beta was quantified by quantitative reverse transcriptase
      polymerase chain reaction analysis. RESULTS: Our data demonstrated that Tlr2
      deficient mice failed to limit Yersinia dissemination from the Peyer's patches
      and succumbed to sepsis independently of nucleotide-binding and oligomerisation
      domain 2 (NOD2). Recognition of both microbiota-derived and myeloid
      differentiation factor 88 (MyD88)-mediated elicitors was found to be critically
      involved in gut protection against Yersinia-induced lethality, while TLR2 was
      dispensable to systemic Yersinia infection. Gene expression analyses revealed
      that optimal epithelial transcript level of the anti-infective Reg3 beta requires
      TLR2 activation. Consistently, Yersinia infection triggered TLR2-dependent Reg3
      beta expression in Peyer's patches. Importantly, oral treatment with exogenous
      TLR2 agonists in germ-free animals was able to further enhance Yersinia-induced
      expression of Reg3 beta and to restore intestinal resistance to Yersinia. Lastly,
      genetic ablation of Reg3 beta resulted in impaired clearance of the bacterial
      load in Peyer's patches. CONCLUSIONS: TLR2/REG3 beta is thus an essential
      component in conditioning epithelial defence signalling pathways against
      bacterial invasion.

PMID- 19174418
TI  - Methylenetetrahydrofolate reductase deficiency and low dietary folate reduce
      tumorigenesis in Apc min/+ mice.
AB  - BACKGROUND: Clinical studies suggest that mild methylenetetrahydrofolate
      reductase (MTHFR) deficiency and high dietary folate may reduce the risk for
      colorectal cancer. There is concern, however, that high folate intake (a
      consequence of food fortification) may enhance tumour growth in individuals with
      pre-existing tumours or genetic predisposition to tumorigenesis. AIM: To
      determine if Mthfr deficiency and low dietary folate influence tumorigenesis in
      mice genetically predisposed to form numerous intestinal adenomas (Apc(min/+)).
      METHODS: Male Apc(min/+) mice were mated with Mthfr(+/-) and/or Mthfr(+/+)
      females. Diets with variable folate content were administered either pre-natally
      or at weaning; tumours were counted in offspring at 10 weeks of age. Plasma
      homocysteine and levels of apoptosis, DNA methylation and nucleotide ratios
      (dUTP:dTTP) in normal (pre-neoplastic) intestine were measured. RESULTS:
      Apc(min/+) mice fed high folate diets from weaning developed more adenomas than
      those fed the folic acid-deficient diet (FADD) or the control diet (CD); Mthfr
      deficiency did not affect adenoma number. However, when the FADD and CD were
      administered to dams prior to conception, throughout pregnancy and continued in
      offspring post-weaning, Apc(min/+) offspring fed FADD developed fewer adenomas
      than those fed CD. Mthfr(+/-) genotype of the mother or of the offspring also
      reduced adenoma numbers in the Apc(min/+) offspring. Adenoma number was inversely
      correlated with plasma homocysteine (r = -0.49, p<0.005, intestinal dUTP/dTTP
      ratios (r = -0.42, p = 0.05), and levels of intestinal apoptosis (r = -0.36, p =
      0.08). CONCLUSIONS: Low dietary folate and Mthfr deficiency reduce adenoma
      formation in mice predisposed to tumorigenesis, possibly through increased
      apoptosis consequent to hyperhomocysteinaemia and nucleotide imbalances.

PMID- 19174419
TI  - Dopamine agonist therapy for hyperprolactinaemia and cardiac valve dysfunction; a
      lot done but much more to do.

PMID- 19174420
TI  - Paediatric and congenital heart disease in South America: an overview.
AB  - Congenital heart diseases are one of the most common structural defects present
      at birth, with an approximate incidence of 8 per 1000 live births. As most
      countries in South America have a high birth rate, they are a significant public
      health concern. This paper provides a brief overview of the burden of congenital
      heart disease in South America, focusing on its local prevalence, facilities for
      treatment and outcomes after medical, surgical or catheter intervention for the
      most common diseases.

PMID- 19174421
TI  - Bioinformatics and breast cancer: what can high-throughput genomic approaches
      actually tell us?
AB  - High-throughput genomic technology has rapidly become a major tool for the study
      of breast cancer. Gene expression profiling has been applied to many areas of
      research from basic science to translational studies, with the potential to
      identify new targets for treatment, mechanisms of resistance and to improve on
      current tools for the analysis of prognosis. However, the sheer scale of the data
      generated along with the number of different protocols, platforms and analysis
      methods can make these studies difficult for clinicians to comprehend. Similarly,
      computational scientists and statisticians that may be called upon to analyse the
      data generated are often unaware of the processes involved in sample collection
      or the relevance and impact of genetics and pathological characteristics. There
      is a pressing need for better understanding of the challenges and limitations of
      microarray approaches, both in experimental design and data analysis. Holistic,
      whole-genome approaches are still relatively new and critics have been quick to
      highlight non-overlapping results from groups testing similar hypotheses.
      However, it is often subtle differences in the experimental design and technology
      that underpin the variation between these studies. Rather than indicating that
      the data are meaningless, this suggests that many findings are real, but highly
      context dependent. This review explores both the current state and potential of
      bioinformatics to bring meaning to high-throughput genomic approaches in the
      understanding of breast cancer.

PMID- 19174422
TI  - Multiple work-related accidents: tracing the role of hearing status and noise
      exposure.
AB  - OBJECTIVES: Our main purpose was to investigate any relationship between noise
      exposure levels in the workplace, degree of hearing loss (HL), and the relative
      risk of accident (OR of single or multiple events). METHODS: We conducted a
      retrospective study of 52 982 male workers aged 16-64 years with long-standing
      exposures to occupational noise over a 5-year period, using "hearing status" and
      "noise exposure" from the registry held by the Quebec National Institute of
      Public Health. Information on work-related accidents was obtained from the Quebec
      Workers' Compensation Board. Hearing threshold level measurements and noise
      exposures were regressed on the numbers of accidents after adjusting for age.
      RESULTS: Exposure to extremely noisy environments (L(eq8h) (equivalent noise
      level for 8 h exposure) > or =90 dBA) is associated with a higher relative risk
      of accident. The severity of hearing impairment (average bilateral hearing
      threshold levels at 3, 4 and 6 kHz) increases the relative risk of single and
      multiple events when threshold levels exceed 15 dB of hearing loss. The relative
      risk of multiple events (four or more) is approximately three times higher among
      severely hearing-impaired workers who are exposed to L(eq8h) > or =90 dBA.
      CONCLUSION: Single and multiple events are associated with high noise exposure
      and hearing status. This suggests that reducing noise exposure contributes to
      increased safety in noisy industries and prevents hearing loss. Hearing-impaired
      workers assigned to noisy workstations should be provided with assistive
      listening devices and efficient communication strategies should be implemented.

PMID- 19174423
TI  - STI management in Tanzanian private drugstores: practices and roles of drug
      sellers.
AB  - OBJECTIVES: To describe the role and possible contribution of private drugstores
      in sexually transmitted infection (STI) management in rural Tanzania. METHODS: A
      cross-sectional study that included drug sellers in private drugstores in eight
      districts of Tanzania. Data collected through interviews with drug sellers and
      the simulated client method presenting a male and female STI case. "QATI" scores
      (Questions, Advice, Treatment and drug Information) were developed to describe
      overall STI management. RESULTS: Although 74% of drug sellers stated that there
      were no STI-related drugs in the store, medications were dispensed in 78% of male
      and 63% of female simulated client visits. The clients were dispensed drugs
      recommended in the Tanzanian guidelines for syndromic management of urethral or
      vaginal discharge in 80% of male and 90% of female cases. Drug sellers dispensed
      antibiotics during 76% of male and 35% of female simulated client visits. Dosage
      regimens were often incorrect and complete syndromic management rarely provided.
      Most drug sellers agreed that it is within their professional role to give
      information on STI treatment (89%) and prevention (95%). Drug-use information was
      almost always provided. Advice was however seldom given and questions
      occasionally asked. Overall STI management was better for men than for women.
      CONCLUSIONS: The drug sellers, although aware of the prescription-only status of
      antibiotics, saw themselves as having a role in STI management and were ready to
      provide drugs. In this resource-limited setting, drug sellers could provide
      effective and safe STI management especially to male patients if given
      appropriate tools to improve practice. The consequences of this for official
      policy need to be discussed.

PMID- 19174424
TI  - Sexually transmitted infection risk exposure among black and minority ethnic
      youth in northwest London: findings from a study translating a sexually
      transmitted infection risk-reduction intervention to the UK setting.
AB  - OBJECTIVES: Young black women are disproportionately affected by sexually
      transmitted infections (STI) in the UK, but effective interventions to address
      this are lacking. The Young Brent Project explored the nature and context of
      sexual risk-taking in young people to inform the translation of an effective
      clinic-based STI reduction intervention (Project SAFE) from the USA to the UK.
      METHODS: One-to-one in-depth interviews (n = 37) and group discussions (n = 10)
      were conducted among men and women aged 15-27 years from different ethnic
      backgrounds recruited from youth and genitourinary medicine clinic settings in
      Brent, London. The interviews explored the context within which STI-related risks
      were assessed, experienced and avoided, the skills needed to recognise risk and
      the barriers to behaviour change. RESULTS: Concurrent sexual partnerships,
      mismatched perceptions and expectations, and barriers to condom use contributed
      to STI risk exposure and difficulties in implementing risk-reduction strategies.
      Women attempted to achieve monogamy, but experienced complex and fluid sexual
      relationships. Low risk awareness, flawed partner risk assessments, negative
      perceptions of condoms and lack of control hindered condom use. Whereas men made
      conscious decisions, women experienced persuasion, deceit and difficulty in
      requesting condom use, particularly with older partners. CONCLUSIONS: Knowledge
      of STI and condom use skills is not enough to equip young people with the means
      to reduce STI risk. Interventions with young women need to place greater emphasis
      on: entering and maintaining healthy relationships; awareness of risks attached
      to different forms of concurrency and how concurrency arises; skills to redress
      power imbalances and building self-esteem.

PMID- 19174425
TI  - Respiratory viruses in bronchoalveolar lavage: a hospital-based cohort study in
      adults.
AB  - BACKGROUND: The epidemiology of respiratory viruses and their potential clinical
      impact when recovered in lower respiratory specimens has not been established in
      the hospital setting. A study was performed to investigate the association
      between positive viral detection and respiratory infection in an at-risk
      population. METHODS: 299 adult patients who underwent bronchoalveolar lavage
      (BAL) procedures were enrolled in a hospital-based prospective cohort study.
      Descriptive epidemiology is presented of 17 different respiratory viruses
      detected by reverse transcription-polymerase chain reaction assays in BAL fluid
      specimens. Multivariate analysis was conducted to identify the clinical
      characteristics independently associated with the presence of virus. RESULTS: Of
      522 BAL fluid specimens analysed, 81% were collected in adult transplant
      recipients or other immunocompromised patients. Overall, PCR assays identified
      viral nucleic acid in 91 BAL fluid samples (17.4%). Similar rates of virus
      positive BAL fluid were found in the different subpopulations studied (p =
      0.113). Coronaviruses were the most frequent (32.3%), followed by rhinovirus
      (22.6%), parainfluenza (19.5%), influenza (9.7%), respiratory synctial virus
      (8.6%), human metapneumovirus (4.2%) and bocavirus (3.1%). Multivariate analysis
      using mixed models showed that respiratory viral infections were associated with
      a lack of antibiotic treatment response (OR 2.2, 95% CI 1.2 to 4.1) and the
      absence of radiological infiltrate (OR 0.3, 95% CI 0.2 to 0.8). In lung
      transplant recipients in whom a respiratory infection was suspected, the
      respiratory viral detection rate was 24.4% compared with 13.8% overall in other
      patients (p = 0.02). CONCLUSIONS: In this cohort of hospitalised adults,
      respiratory viruses detected in BAL fluid specimens were associated with
      respiratory symptoms, absence of radiological infiltrates and a poor response to
      antibiotic therapy.

PMID- 19174426
TI  - Lifestyle impact on lifetime bone loss in women and men: the Tromso Study.
AB  - A physically active, nonsmoking lifestyle with weight maintenance positively
      influences bone health. The authors estimated the effect of lifestyles on peak
      bone mass and lifetime bone loss in the Tromso Study, Norway. Bone mineral
      density (BMD) was measured at distal and ultradistal forearm sites with single x
      ray absorptiometric devices in 7,948 men and women aged 24-84 years in 1994-1995
      and repeated in 2001 in 6,182 subjects. BMD was significantly higher at peak than
      at old age. However, the difference, estimated as lifetime loss, varied between
      lifestyle groups. Lifetime loss in nonsmoking, physically active men with a body
      mass index of 25 kg/m(2) compared with smoking, inactive, and lean men was 15.9%
      and 25.9% at the distal site and 17.5% and 29.7% at the ultradistal site,
      respectively. In women, the corresponding loss estimates were 34.4% and 45.7% and
      35.6% and 55.7%, respectively. The differences in BMD at the age of 80 years
      correspond to an increased forearm fracture risk of 69% in men and 85% in women
      with greatest bone loss. A lifestyle including nonsmoking, a high physical
      activity level, and a high body weight reduces bone loss and fracture risk in
      both sexes, with increasing effect from peak bone mass to old age.

PMID- 19174427
TI  - Atrial fibrillation following cardiac surgery: clinical features and preventative
      strategies.
AB  - Atrial fibrillation (AF) is a common complication of cardiac surgery, with an
      increasing incidence. Post-operative AF results in many complications and
      increased healthcare resources. Despite substantial interest in the prediction
      and prevention of post-operative AF, as well as guidelines for the management of
      this common arrhythmia, there is still some uncertainty about appropriate risk
      stratification and management. The aim of this review article is to provide an
      overview of clinical predictive features for the development of AF following
      cardiac surgery and suitable preventive measures, using both antiarrhythmic and
      non-antiarrhythmic strategies.

PMID- 19174430
TI  - Listeriosis remains a cause for concern in Europe.

PMID- 19174428
TI  - Interindividual variability in the response to oral antiplatelet drugs: a
      position paper of the Working Group on antiplatelet drugs resistance appointed by
      the Section of Cardiovascular Interventions of the Polish Cardiac Society,
      endorsed by the Working Group on Thrombosis of the European Society of
      Cardiology.
AB  - Oral antiplatelet drugs are a cornerstone of modern pharmacotherapy in
      cardiovascular atherothrombotic diseases. The efficacy of acetylsalicylic acid
      (ASA, aspirin) and clopidogrel in decreasing the risk of adverse events in
      coronary heart disease patients has been well established in the past 20 years.
      Despite chronic oral antiplatelet therapy, a number of atherothombotic events
      continue to occur. In recent years, a number of reports in the literature have
      shown possible relationships between residual platelet activity, as measured with
      a variety of laboratory tests, and clinical outcome, raising the possibility that
      'resistance' to oral antiplatelet drugs may underlie many such clinical adverse
      events. The present position paper, conveyed within a group of clinical
      cardiologists with expertise in thrombosis appointed by the Section of
      Cardiovascular Interventions of the Polish Cardiac Society, has been further
      elaborated and endorsed by the Working Group on Thrombosis of the European
      Society of Cardiology. It aims at summarizing the main findings in this complex
      area, issuing opinions in cases of high controversy, and fostering future
      research in this area to obtain reliable laboratory and clinical data for the
      resolution of the many problems still open.

PMID- 19174431
TI  - Obama overturns ban on federal funding of family planning organisations that
      promote abortion.

PMID- 19174432
TI  - Unicef appeals for $1bn to help children and women in humanitarian emergencies.

PMID- 19174433
TI  - Heart failure with a normal ejection fraction.

PMID- 19174434
TI  - Use of primary care electronic medical record database in drug efficacy research
      on cardiovascular outcomes: comparison of database and randomised controlled
      trial findings.
AB  - OBJECTIVES: To determine whether observational studies that use an electronic
      medical record database can provide valid results of therapeutic effectiveness
      and to develop new methods to enhance validity. DESIGN: Data from the UK general
      practice research database (GPRD) were used to replicate previously performed
      randomised controlled trials, to the extent that was feasible aside from
      randomisation. Studies Six published randomised controlled trials. MAIN OUTCOME
      MEASURE: Cardiovascular outcomes analysed by hazard ratios calculated with
      standard biostatistical methods and a new analytical technique, prior event rate
      ratio (PERR) adjustment. RESULTS: In nine of 17 outcome comparisons, there were
      no significant differences between results of randomised controlled trials and
      database studies analysed using standard biostatistical methods or PERR analysis.
      In eight comparisons, Cox adjusted hazard ratios in the database differed
      significantly from the results of the randomised controlled trials, suggesting
      unmeasured confounding. In seven of these eight, PERR adjusted hazard ratios
      differed significantly from Cox adjusted hazard ratios, whereas in five they
      didn't differ significantly, and in three were more similar to the hazard ratio
      from the randomised controlled trial, yielding PERR results more similar to the
      randomised controlled trial than Cox (P<0.05). CONCLUSIONS: Although
      observational studies using databases are subject to unmeasured confounding, our
      new analytical technique (PERR), applied here to cardiovascular outcomes, worked
      well to identify and reduce the effects of such confounding. These results
      suggest that electronic medical record databases can be useful to investigate
      therapeutic effectiveness.

PMID- 19174435
TI  - Cello scrotum confession. Murphy's lore.

PMID- 19174436
TI  - Donors pledge $630m to help boost global polio eradication.

PMID- 19174437
TI  - Does acupuncture relieve pain?

PMID- 19174438
TI  - Acupuncture treatment for pain: systematic review of randomised clinical trials
      with acupuncture, placebo acupuncture, and no acupuncture groups.
AB  - OBJECTIVES: To study the analgesic effect of acupuncture and placebo acupuncture
      and to explore whether the type of the placebo acupuncture is associated with the
      estimated effect of acupuncture. DESIGN: Systematic review and meta-analysis of
      three armed randomised clinical trials. DATA SOURCES: Cochrane Library, Medline,
      Embase, Biological Abstracts, and PsycLIT. Data extraction and analysis
      Standardised mean differences from each trial were used to estimate the effect of
      acupuncture and placebo acupuncture. The different types of placebo acupuncture
      were ranked from 1 to 5 according to assessment of the possibility of a
      physiological effect, and this ranking was meta-regressed with the effect of
      acupuncture. DATA SYNTHESIS: Thirteen trials (3025 patients) involving a variety
      of pain conditions were eligible. The allocation of patients was adequately
      concealed in eight trials. The clinicians managing the acupuncture and placebo
      acupuncture treatments were not blinded in any of the trials. One clearly
      outlying trial (70 patients) was excluded. A small difference was found between
      acupuncture and placebo acupuncture: standardised mean difference -0.17 (95%
      confidence interval -0.26 to -0.08), corresponding to 4 mm (2 mm to 6 mm) on a
      100 mm visual analogue scale. No statistically significant heterogeneity was
      present (P=0.10, I(2)=36%). A moderate difference was found between placebo
      acupuncture and no acupuncture: standardised mean difference -0.42 (-0.60 to 
      0.23). However, considerable heterogeneity (P<0.001, I(2)=66%) was also found, as
      large trials reported both small and large effects of placebo. No association was
      detected between the type of placebo acupuncture and the effect of acupuncture
      (P=0.60). CONCLUSIONS: A small analgesic effect of acupuncture was found, which
      seems to lack clinical relevance and cannot be clearly distinguished from bias.
      Whether needling at acupuncture points, or at any site, reduces pain
      independently of the psychological impact of the treatment ritual is unclear.

PMID- 19174439
TI  - Change in moles linked to use of unlicensed "sun tan jab".

PMID- 19174440
TI  - EC, don't let drug companies give information to the public.

PMID- 19174441
TI  - Drug companies and the public. EC proposal can be defeated.

PMID- 19174442
TI  - Breast screening: the facts--or maybe not.

PMID- 19174443
TI  - Selective echocardiographic analysis of epicardial and endocardial left
      ventricular rotational mechanics in an animal model of pericardial adhesions.
AB  - AIMS: Diagnosis of pericardial adhesions is challenging. Twisting of the left
      ventricle (LV) is essential for normal LV functioning. We experimentally
      characterized the impact of pericardial adhesions on epicardial and endocardial
      LV rotational mechanics with velocity vector imaging (VVI). METHODS AND RESULTS:
      In nine open-chest pigs, the heart was exposed while preserving the pericardium.
      Early-stage pericardial adhesions were simulated by instilling tissue glue to
      pericardial space. Using VVI, LV rotational mechanics was quantitatively assessed
      endocardially and epicardially along with haemodynamic data at baseline and
      following the experimental intervention. End-diastolic volume, ejection fraction,
      stroke volume, late diastolic filling velocity, and LV endocardial torsion
      decreased significantly. LV epicardial torsion showed only a trend towards
      decrease (P = 0.141). Endocardial twist and torsion decreased significantly (P =
      0.007) from 8.6 +/- 2.2 degree and 1.497 +/- 0.397 degree/cm to 5.3 +/- 1.8
      degree and 0.97 +/- 0.38 degree/cm, respectively; epicardial twist showed a trend
      towards a decrease in its magnitude. Gradients of endocardial/epicardial twist
      and torsion did not significantly change. CONCLUSION: The model suggests that
      early-stage pericardial adhesions reduce both epicardial and endocardial LV twist
      and torsion without a significant alteration in their transmural gradient.
      Selective endocardial/epicardial analysis of LV twisting mechanics may have a
      diagnostic role in detection of early formation of pericardial adhesions.

PMID- 19174444
TI  - Speckle tracking for left ventricle performance in young athletes with bicuspid
      aortic valve and mild aortic regurgitation.
AB  - AIMS: Longitudinal peak systolic strain (LPSS) quantifies regional and global
      heart function. Few data are available on left ventricle (LV) performance in
      young athletes with bicuspid aortic valve (BAV), where a pattern of mild aortic
      insufficiency is relatively frequent, and the ejection fraction (EF) is often
      normal for a long time. We report the measurement of LV strain in young BAV
      athletes. METHODS AND RESULTS: Three groups (20 athletes with BAV, 20 healthy
      athletes, and 20 sedentary healthy subjects, all aged 25 +/- 3 years) underwent
      standard echo examination to evaluate LPSS at the basal and medium-apical
      segments of the lateral wall (LW) and interventricular septum (IVS) of the LV.
      LPSS was within the normal range; however, in BAV athletes, the LPSS of the basal
      segments tended to be lower (S%IVS(basal), -17.7 +/- 2.7; S%LW(basal), -14.2 +/-
      2.2; S%IVS(med-apic), -21 +/- 3.5; S%LW(med-apic), -18.8 +/- 4.2), producing a
      gradient from basal to apical regions. The EF was normal in all subjects.
      CONCLUSION: Young trained BAV athletes have normal LV performance. Nevertheless,
      these athletes tend to have lower strain than healthy subjects in the LV basal
      segments. The clinical implications of this finding are uncertain and require
      further investigation.

PMID- 19174445
TI  - Large left ventricular metastasis causing left ventricular outflow tract
      obstruction and haemolysis.
AB  - Although post-mortem studies would suggest that cardiac metastases occur
      frequently, many of these metastases remain clinically silent. However,
      symptomatic lesions may also remain unrecognized due to overshadowing by other
      symptoms of the primary malignancy. Patients undergoing treatment for cancer are
      not routinely screened using echocardiography, unless their chemotherapeutic
      regimen includes cardiotoxic agents. The current era of research and development
      of targeted biological agents (such as trastuzumab and epidermal growth factor
      receptor inhibitors) for cancer may lead to prolonged survival of oncology
      patients. In future, metastases that were once rare may become increasingly
      recognized as these new treatments augment the natural history of the disease.
      There have been several case reports of small, asymptomatic left ventricular
      metastases, but clinically significant ventricular metastases are very rare.
      There are no reports in the current literature of a symptomatic ventricular
      metastasis, occurring in the absence of other metastatic disease. We report an
      unusual case of a large solitary ventricular metastasis, leading to left
      ventricular outflow tract obstruction and haemodynamic compromise.
      Echocardiographic imaging led to the diagnosis of a recurrence of soft-tissue
      fibrosarcoma 9 years after original resection.

PMID- 19174446
TI  - Two types of thalamocortical projections from the motor thalamic nuclei of the
      rat: a single neuron-tracing study using viral vectors.
AB  - The axonal arborization of single motor thalamic neurons was examined in rat
      brain using a viral vector expressing membrane-targeted palmitoylation site
      attached green fluorescent protein (palGFP). We first divided the ventral
      anterior-ventral lateral motor thalamic nuclei into 1) the rostromedial portion,
      which was designated inhibitory afferent-dominant zone (IZ) with intense
      glutamate decarboxylase immunoreactivity and weak vesicular glutamate transporter
      2 immunoreactivity, and 2) the caudolateral portion, named excitatory subcortical
      afferent-dominant zone (EZ) with the reversed immunoreactivity profile. We then
      labeled 38 motor thalamic neurons in 29 hemispheres by injecting a diluted palGFP
      Sindbis virus solution and isolated 10 IZ and EZ neurons for reconstruction. All
      the reconstructed IZ neurons widely projected not only to the cerebral cortex but
      also to the neostriatum, whereas the EZ neurons sent axons almost exclusively to
      the cortex. More interestingly, 47-66% of axon varicosities of IZ neurons were
      observed in layer I of cortical areas. In contrast, only 2-15% of varicosities of
      EZ neurons were found in layer I, most varicosities being located in middle
      layers. These results suggest that 2 forms of information from the basal ganglia
      and cerebellum are differentially supplied to apical and basal dendrites,
      respectively, of cortical pyramidal neurons and integrated to produce a motor
      execution command.

PMID- 19174447
TI  - Evidence of 'genuine empty follicles' in follicular aspirate: a case report.
AB  - Failure to retrieve oocytes after normal ovarian stimulation has been labeled
      'empty follicle syndrome' (EFS). The existence of genuine EFS has been questioned
      and is still controversial. Here, we report an unusual case in which an
      extraordinary number of empty follicle-like structures were identified in the
      ovarian aspirate at the time of retrieval. A 31-year-old woman presented with a 4
      year history of primary infertility and underwent ovulation induction. The
      patient was given hCG and oocyte retrieval was performed 36 h later. During the
      oocyte retrieval, more than 200 tiny structures resembling pre-antral follicles
      were noted in the ovarian aspirate. They exhibited two to three layers of
      granulosa cells and appeared to enclose an immature oocyte. They showed a great
      variation in size ranging between 40 and 80 microm. These structures were further
      characterized by electron microscopy and cultivated in vitro to assess hormone
      secretion. The follicles were found to be devoid of oocytes, but each had a
      readily identifiable zona. Hormone assays revealed that these follicles were
      secreting increasing levels of estradiol. A second in vitro fertilization attempt
      gave similar results. These data are suggestive of some failure in the oocyte
      maturation process. We speculate that this may be the first actual evidence to
      support the existence of true empty follicles, which if left to grow in vivo
      might lead to empty graffian follicles and genuine EFS.

PMID- 19174448
TI  - Blocking glutamate receptors in the waist area of the parabrachial nucleus
      decreases taste reactivity behaviors in conscious rats.
AB  - The "waist" area (W) of the parabrachial nucleus contains neurons that receive
      orosensory input and play a role in the initiation of oromotor behaviors.
      Immunohistochemical data indicate that neurons in W receive glutamatergic input
      and express glutamate receptors, but a behavioral role for glutamate
      neurotransmission within W has not been investigated. To determine the role of
      specific glutamate receptors in taste reactivity behaviors, glutamate receptor
      blockers were delivered into W by reverse microdialysis during intraoral infusion
      of 0.1 M sodium chloride, 0.1 M sucrose, 0.03 M hydrochloric acid, and 0.003 M
      quinine hydrochloride. Blocking alpha-amino-3-hydroxy-5-methyl
      isoxazolepropionate (AMPA)/kainate ionotropic glutamate receptors in W with 6
      cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX) reduced ingestive taste
      reactivity behaviors to each tastant by 72-85% compared with baseline levels (P's
      < 0.05). Blocking N-methyl-D-aspartate receptors as well as type 1 and group III
      metabotropic glutamate receptors had minor effects on taste reactivity responses
      to the tastants. These data provide strong evidence for a behavioral role of
      glutamatergic neurotransmission in W in conscious rats.

PMID- 19174450
TI  - Pathological characteristics of very young (< or = 30 years) breast cancer
      patients: a single-institution experience from Turkey.

PMID- 19174451
TI  - High risk of cardiac dysfunction after treatment of secondary acute myeloid
      leukaemia to breast cancer.

PMID- 19174452
TI  - A risk model for severe anemia to select cancer patients for primary prophylaxis
      with epoetin alpha: a prospective randomized controlled trial of the ELYPSE study
      group.
AB  - BACKGROUND: Epoetin (EPO) administration reduces the need for transfusion.
      Identifying patients at high risk of anemia requiring red blood cell (RBC)
      transfusion is needed. This multicentric phase III trial tested epoetin alpha
      (EPOalpha) administration according to our risk model on the basis of three
      clinical parameters: hemoglobin (Hb) <12 g/dl, lymphocytes <or=700/microl, and/or
      performance status (PS) >1. PATIENTS AND METHODS: Patients >or=18 years with
      chemotherapy-treated solid or hematologic tumors were randomized to 150 UI/kg/TIW
      s.c. EPOalpha (arm 1) or no EPOalpha (arm 2) and stratified on Hb level at day 0,
      lymphocyte count, and PS. The primary end point was transfusion rate; secondary
      end points included overall survival (OS), safety, and quality of life. RESULTS:
      From September 2000 to January 2005, 218 patients (median age 64 years, 42.7%
      males) with principally breast cancer, sarcoma, or lung carcinoma were included.
      In total, 93% patients had PS >1 and 35% had <or=700/microl lymphocytes. Baseline
      Hb levels were 10.1 g/dl (range 6.9-11.9). Two hundred and thirteen patients were
      assessable for the primary end point: 36% received RBC in arm 1 and 58% in arm 2
      (P = 0.0012). Median OS was 7.6 [95% confidence interval (CI): 5-12] and 6 (95%
      CI: 5-8) months in arms 1 and 2, respectively. Median OS was significantly worse
      for patients with three prognostic factors (3.6 months) compared with two factors
      (8.3 months) (P < 0.001). No difference in toxicity (47% versus 41%) or
      thrombovascular events (4.5% versus 3.7%) was observed. CONCLUSION: Patients at
      high risk for RBC transfusion according to the ELYPSE model could be given
      prophylactic EPO with significantly reduced RBC transfusions and no significant
      impact on side-effects, progression-free survival, and OS.

PMID- 19174453
TI  - Sentinel node biopsy compared with complete axillary dissection for staging early
      breast cancer with clinically negative lymph nodes: results of randomized trial.
AB  - BACKGROUND: Sentinel lymph node (SLN) staging is currently used to avoid complete
      axillary dissection in breast cancer patients with negative SLNs. Evidence of a
      similar efficacy, in terms of survival and regional control, of this strategy as
      compared with axillary resection is based on few clinical trials. In 1998, we
      started a randomized study comparing the two strategies, and we present here its
      results. MATERIALS AND METHODS: Patients were randomly assigned to sentinel lymph
      node biopsy (SLNB) and axillary dissection [axillary lymph node dissection (ALND
      arm)] or to SLNB plus axillary resection if SLNs contained metastases (SLNB arm).
      Main end points were overall survival (OS) and axillary recurrence. RESULTS: One
      hundred and fifteen patients were assigned to the ALND arm and 110 to the SLNB
      arm. A positive SLN was found in 27 patients in the ALND arm and in 31 in the
      SLNB arm. Overall accuracy of SLNB was 93.0%. Sensitivity and negative predictive
      values were 77.1% and 91.1%, respectively. At a median follow-up of 5.5 years, no
      axillary recurrence was observed in the SLNB arm. OS and event-free survival were
      not statistically different between the two arms. CONCLUSIONS: The SLNB procedure
      does not appear inferior to conventional ALND for the subset of patients here
      considered.

PMID- 19174449
TI  - Breast cancer in young women and its impact on reproductive function.
AB  - BACKGROUND: Breast cancer is the most common cancer in women in developed
      countries, and 12% of breast cancer occurs in women 20-34 years. Survival from
      breast cancer has significantly improved, and the potential late effects of
      treatment and the impact on quality of life have become increasingly important.
      Young women constitute a minority of breast cancer patients, but commonly have
      distinct concerns and issues compared with older women, including queries
      regarding fertility, contraception and pregnancy. Further, they are more likely
      than older women to have questions regarding potential side effects of therapy
      and risk of relapse or a new primary. In addition, many will have symptoms
      associated with treatment and they present a management challenge. Reproductive
      medicine specialists and gynaecologists commonly see these women either shortly
      after initial diagnosis or following adjuvant therapy and should be aware of
      current management of breast cancer, the options for women at increased genetic
      risk, the prognosis of patients with early stage breast cancer and how adjuvant
      systemic treatments may impact reproductive function. METHODS: No systematic
      literature search was done. The review focuses on the current management of
      breast cancer in young women and the impact of treatment on reproductive function
      and subsequent management. With reference to key studies and meta-analyses, we
      highlight controversies and current unanswered questions regarding patient
      management. RESULTS: Chemotherapy for breast cancer is likely to negatively
      impact on reproductive function. A number of interventions are available which
      may increase the likelihood of future successful pregnancy, but the relative
      safety of these interventions is not well established. For those who do conceive
      following breast cancer, there is no good evidence that pregnancy is detrimental
      to survival. We review current treatment; effects on reproductive function;
      preservation of fertility; contraception; pregnancy; breastfeeding and management
      of menopausal symptoms following breast cancer. CONCLUSION: This paper provides
      an update on the management of breast cancer in young women and is targeted at
      reproductive medicine specialists and gynaecologists.

PMID- 19174454
TI  - Susceptibilities of Haemophilus influenzae, Streptococcus pneumoniae, including
      serotype 19A, and Moraxella catarrhalis paediatric isolates from 2005 to 2007 to
      commonly used antibiotics.
AB  - OBJECTIVES: The aim of this study was to evaluate susceptibility to common
      paediatric antibiotics for Streptococcus pneumoniae, non-typeable Haemophilus
      influenzae and Moraxella catarrhalis isolated from 2005 through 2007. METHODS:
      Microdilution MIC assays were performed using CLSI-approved methods. S.
      pneumoniae 19A strains were identified by quellung reaction. RESULTS: Among 143
      non-typeable H. influenzae, 42% produced beta-lactamase. By 2007 breakpoints
      (PK/PD:CLSI), percentage susceptibility for non-typeable H. influenzae was:
      ceftriaxone = cefixime = high-dose amoxicillin/clavulanate (all 100%:100%) >
      standard-dose amoxicillin/clavulanate (91.6%:100%) > cefuroxime axetil
      (88.1%:99.3%) > cefdinir (83.9%:100%) > trimethoprim/sulfamethoxazole
      (73.4%:73.4%) >high-dose amoxicillin (58%:58%) > standard-dose amoxicillin
      (55.2%:58%) > cefprozil (28.7%:83.2%) > cefaclor (3.5%:83.2%) > azithromycin
      (0%:87.4%). Of 208 S. pneumoniae (42 serotype 19A), 86 were penicillin
      susceptible, 60 were penicillin-intermediate and 62 were penicillin-resistant by
      2007 CLSI breakpoints. Percentage susceptibility for all S. pneumoniae/19A by PD
      breakpoints was: ceftriaxone (95.2%/86.1%) > high-dose amoxicillin (89.4%/58.3%)
      > clindamycin (85%/58.3%) > standard-dose amoxicillin (73.5%/33.3%) > cefuroxime
      axetil (69.2%/36.1%), cefprozil (67.3%/33.3%) > cefdinir (59.1%/33.3%) > cefixime
      (57.7%/33.3%) > azithromycin (56.7%/33.3%) > trimethoprim/sulfamethoxazole
      (50.5%/25%) > penicillin (41.3%/19.4%) > cefaclor (28.8%/8.3%). Percentage M.
      catarrhalis (n = 62) susceptibility by PK/PD breakpoints was: high-dose
      amoxicillin/clavulanate = cefixime (100%) > azithromycin (98.4%) > ceftriaxone
      (96.8%) > standard-dose amoxicillin/clavulanate (88.7%) > cefdinir (80.6%) >
      cefprozil = cefuroxime axetil (37.1%) > high-dose amoxicillin (11.2%) > cefaclor
      (6.5%) > standard-dose amoxicillin (4.8%). CONCLUSIONS: Despite high rates of
      beta-lactamase production among non-typeable H. influenzae and M. catarrhalis,
      multiple oral treatment options exist for non-typeable H. influenzae and M.
      catarrhalis. Multidrug-resistant serotype 19A S. pneumoniae ( approximately 20%)
      limits treatment options for ambulatory S. pneumoniae respiratory disease.

PMID- 19174455
TI  - Developmentally early and late onset of Rps10 silencing in Arabidopsis thaliana:
      genetic and environmental regulation.
AB  - Transgene dosage, silencing competence of the transgene loci, and photoperiod
      conditions were found to regulate the onset and efficiency of Rps10 silencing in
      two independent transgenic lines of Arabidopsis thaliana. The Rps10 gene encodes
      the S10 protein which is part of the small subunit of mitochondrial ribosomes.
      Homozygous plants presented developmentally early onset of silencing, a very
      efficient decrease in the level of Rps10 transcripts, as well as a severe and
      uniform phenotype called P1. P1 plants either died during the vegetative growth
      phase or were rescued by reversion resulting from inactivation of silencing. A
      wide variety of morphological and developmental abnormalities observed within the
      hemizygous transformants allowed their classification into three categories P2,
      P3, and P4. The most severe and early was the P2 phenotype found in only one
      transgenic line and most probably resulting from high competence of the transgene
      loci. Developmentally late onset of silencing occurred only in the short day
      photoperiod and was characteristic for the P3 and P4 plants. This phenomenon was
      attributed to conditions favourable to silencing achieved in the short day
      photoperiod, e.g. a greatly prolonged vegetative phase accompanied by a gradual
      increase of the level of Rps10 transcripts. To the best of our knowledge, this is
      the first report indicating that the onset of silencing depends on the
      photoperiod conditions in A. thaliana.

PMID- 19174456
TI  - Enzyme activities and subcellular localization of members of the Arabidopsis
      glutathione transferase superfamily.
AB  - Enzyme screens with Strep-tagged recombinant proteins and expression studies with
      the respective green fluorescent protein (GFP) fusions have been employed to
      examine the functional activities and subcellular localization of members of the
      Arabidopsis glutathione transferase (GST) superfamily. Fifty-one of 54 GST family
      members were transcribed and 41 found to express as functional glutathione
      dependent enzymes in Escherichia coli. Functional redundancy was observed and in
      particular three theta (T) class GSTs showed conserved activities as
      hydroperoxide-reducing glutathione peroxidases (GPOXs). When expressed in tobacco
      as GFP fusions, all three GSTTs localized to the peroxisome, where their GPOX
      activity could prevent membrane damage arising from fatty acid oxidation. Through
      alternative splicing, two of these GSTTs form fusions with Myb transcription
      factor-like domains. Examination of one of these variants showed discrete
      localization within the nucleus, possibly serving a role in reducing nucleic acid
      hydroperoxides or in signalling. Based on this unexpected differential sub
      cellular localization, 15 other GST family members were expressed as GFP fusions
      in tobacco. Most accumulated in the cytosol, but GSTU12 localized to the nucleus,
      a family member resembling a bacterial tetrachlorohydroquinone dehalogenase
      selectively associated with the plasma membrane, and a lambda GSTL2 was partially
      directed to the peroxisome after removal of a putative chloroplast transit
      peptide. Based on the results obtained with the GSTTs, it was concluded that
      these proteins can exert identical protective functions in differing subcellular
      compartments.

PMID- 19174457
TI  - Ubiquitous distribution and different subcellular localization of sorbitol
      dehydrogenase in fruit and leaf of apple.
AB  - NAD(+)-dependent sorbitol dehydrogenase (NAD-SDH, EC 1.1.1.14), a key enzyme in
      sorbitol metabolism, plays an important role in regulating sink strength and
      determining the quality of apple fruit. Understanding the tissue and subcellular
      localization of NAD-SDH is helpful for understanding sorbitol metabolism in the
      apple. In this study, two NAD-SDH cDNA sequences were isolated from apple fruits
      (Malus domestica Borkh cv. Starkrimson) and named MdSDH5 and MdSDH6.
      Immunohistochemical analysis revealed that NAD-SDH is distributed in both the
      flesh and the vascular tissue of the fruit, and the vascular tissue and mesophyll
      tissue in the young and old leaves, indicating that it is a ubiquitous protein
      expressed in both sink and source organs. Immunogold electron microscopy analysis
      demonstrated that NAD-SDH is localized mainly in the cytoplasm and chloroplast of
      the fruit and leaves. The chloroplast localization of NAD-SDH was confirmed by
      the transient expression of MdSDH5-GFP and MdSDH6-GFP in the mesophyll protoplast
      of Arabidopsis. NAD-SDH was also found in electron opaque deposits of vacuoles in
      young and mature leaves. These data show that NAD-SDH has different subcellular
      localizations in fruit and leaves, indicating that it might play a different role
      in sorbitol metabolism in different tissues of apple.

PMID- 19174458
TI  - Climate change and tropical marine agriculture.
AB  - The coral reef ecosystem forms part of a 'seascape' that includes land-based
      ecosystems such as mangroves and forests, and ideally should form a complete
      system for conservation and management. Aquaculture, including artisanal fishing
      for fish and invertebrates, shrimp farming, and seaweed farming, is a major part
      of the farming and gleaning practices of many tropical communities, particularly
      on small islands, and depends upon the integrity of the reefs. Climate change is
      making major impacts on these communities, not least through global warming and
      high CO(2) concentrations. Corals grow within very narrow limits of temperature,
      provide livelihoods for millions of people in tropical areas, and are under
      serious threat from a variety of environmental and climate extremes. Corals
      survive and grow through a symbiotic relationship with photosynthetic algae:
      zooxanthellae. Such systems apply highly co-operative regulation to minimize the
      fluctuation of metabolite concentration profiles in the face of transient
      perturbations. This review will discuss research on how climate influences reef
      ecosystems, and how science can lead to conservation actions, with benefits for
      the human populations reliant on the reefs for their survival.

PMID- 19174459
TI  - The gene regulatory network for root epidermal cell-type pattern formation in
      Arabidopsis.
AB  - A fundamental aspect of multicellular development is the patterning of distinct
      cell types in appropriate locations. In this review, the molecular genetic
      control of cell-type pattern formation in the root epidermis of Arabidopsis
      thaliana is summarized. This developmental system represents a simple and
      genetically tractable example of plant cell patterning. The distribution of the
      two epidermal cell types, root-hair cells and non-hair cells, are generated by a
      combination of positional signalling and lateral inhibition mechanisms. In
      addition, recent evidence suggests that reinforcing mechanisms are used to ensure
      that the initial cell fate choice is adopted in a robust manner.

PMID- 19174460
TI  - Low responsiveness of grapevine flowers and berries at fruit set to UV-C
      irradiation.
AB  - In grapevine, stimulation of defence responses was evidenced in response to
      various types of abiotic stresses in both leaves and berries, as revealed by the
      increasing expression of genes encoding defence-related proteins or the
      stimulation of their corresponding activities. However, the capability of
      inflorescences to respond to abiotic stresses has never been investigated.
      Therefore, plant defence reactions in response to UV-C irradiation were followed
      in inflorescences and young clusters focusing on both bunchstems (peduncle and
      pedicels) and developing flowers/berries from separated floral buds stage
      [Biologische Bundesanstalt, Bundessortenamt and CHemical industry (BBCH) stage
      57] to groat-sized berries stage (BBCH 73). For this purpose, the expression of
      various genes coding for pathogenesis-related (PR) proteins (class I and III
      chitinases, Chi1b and CH3; beta-1,3-glucanase, GLUC), an enzyme of the
      phenylpropanoid pathway (phenylalanine ammonia-lyase, PAL), and stilbene synthase
      (STS) was analysed in parallel with variations of chitinase activity and the
      accumulation of the phytoalexin resveratrol. Multiple defence responses were
      induced in bunchstems of both inflorescences and clusters following UV-C
      treatment. First, expression of genes encoding PR proteins was stimulated and
      chitinase activity was enhanced. Secondly, PAL and STS expression increased in
      association with resveratrol accumulation. Amazingly, none of the tested defence
      processes was induced in grapevine flowers following UV-C exposure, whatever the
      stage analysed. Similarly, in berries at fruit set, induction of gene expression
      was weak and neither an increase in chitinase activity nor resveratrol synthesis
      was noticed. However, in groat-sized berries, responsiveness to UV-C increased,
      as revealed by the induction of CH3, PAL, and STS expression, together with
      resveratrol accumulation. The differential responsiveness between bunchstems,
      flowers, and berries is discussed.

PMID- 19174461
TI  - Co-ordinated regulation of flowering time, plant architecture and growth by
      FASCICULATE: the pepper orthologue of SELF PRUNING.
AB  - Wild peppers (Capsicum spp.) are either annual or perennial in their native
      habitat and their shoot architecture is dictated by their sympodial growth habit.
      To study shoot architecture in pepper, sympodial development is described in wild
      type and in the classical recessive fasciculate (fa) mutation. The basic
      sympodial unit in wild-type pepper comprises two leaves and a single terminal
      flower. fasciculate plants are characterized by the formation of floral clusters
      separated by short internodes and miniature leaves and by early flowering.
      Developmental analysis of these clusters revealed shorter sympodial units and,
      often, precocious termination prior to sympodial leaf formation. fa was mapped to
      pepper chromosome 6, in a region corresponding to the tomato SELF-PRUNING (SP)
      locus, the homologue of TFL1 of Arabidopsis. Sequence comparison between wild
      type and fa plants revealed a duplication of the second exon in the mutants'
      orthologue of SP, leading to the formation of a premature stop codon. Ectopic
      expression of FASCICULATE complemented the Arabidopsis tfl1 mutant plants and as
      expected, stimulated late flowering. In agreement with the major effect of
      FASCICULATE imposed on sympodial development, the gene transcripts were localized
      to the centre of sympodial shoots but could not be detected in the primary shoot.
      The wide range of pleiotropic effects on plant architecture mediated by a single
      'flowering' gene, suggests that it is used to co-ordinate many developmental
      events, and thus may underlie some of the widespread variation in the Solanaceae
      shoot architecture.

PMID- 19174462
TI  - Trafficking of storage proteins in developing grain of wheat.
AB  - The processing properties of the wheat flour are largely determined by the
      structures and interactions of the grain storage proteins (also called gluten
      proteins) which form a continuous visco-elastic network in dough. Wheat gluten
      proteins are classically divided into two groups, the monomeric gliadins and the
      polymeric glutenins, with the latter being further classified into low molecular
      weight (LMW) and high molecular weight (HMW) subunits. The synthesis, folding and
      deposition of the gluten proteins take place within the endomembrane system of
      the plant cell. However, determination of the precise routes of trafficking and
      deposition of individual gluten proteins in developing wheat grain has been
      limited in the past by the difficulty of developing monospecific antibodies. To
      overcome this limitation, a single gluten protein (a LMW subunit) was expressed
      in transgenic wheat with a C-terminal epitope tag, allowing the protein to be
      located in the cells of the developing grain using highly specific antibodies.
      This approach was also combined with the use of wider specificity antibodies to
      compare the trafficking and deposition of different gluten protein groups within
      the same endosperm cells. These studies are in agreement with previous
      suggestions that two trafficking pathways occur in wheat, with the proteins
      either being transported via the Golgi apparatus into the vacuole or accumulating
      directly within the lumen of the ER. They also suggest that the same individual
      protein could be trafficked by either pathway, possibly depending on the stage of
      development, and that segregation of gluten proteins both between and within
      protein bodies may occur.

PMID- 19174463
TI  - Involvement of SIRT7 in resumption of rDNA transcription at the exit from
      mitosis.
AB  - Sirtuins, also designated class III histone deacetylases, are implicated in the
      regulation of cell division, apoptosis, DNA damage repair, genomic silencing and
      longevity. The nucleolar Sirtuin7 (SIRT7) was reported to be involved in the
      regulation of ribosomal gene (rDNA) transcription, but there are no data
      concerning the regulation of SIRT7 during the cell cycle. Here we have analyzed
      the behavior of endogenous SIRT7 during mitosis, while rDNA transcription is
      repressed. SIRT7 remains associated with nucleolar organizer regions, as does the
      RNA polymerase I machinery. SIRT7 directly interacts with the rDNA transcription
      factor UBF. Moreover, SIRT7 is phosphorylated via the CDK1-cyclin B pathway
      during mitosis and dephosphorylated by a phosphatase sensitive to okadaic acid at
      the exit from mitosis before onset of rDNA transcription. Interestingly,
      dephosphorylation events induce a conformational modification of the carboxy
      terminal region of SIRT7 before the release of mitotic repression of rDNA
      transcription. As SIRT7 activity is required to resume rDNA transcription in
      telophase, we propose that this conformational modification regulates onset of
      rDNA transcription.

PMID- 19174464
TI  - Mars, a Drosophila protein related to vertebrate HURP, is required for the
      attachment of centrosomes to the mitotic spindle during syncytial nuclear
      divisions.
AB  - The formation of the mitotic spindle is controlled by the microtubule organizing
      activity of the centrosomes and by the effects of chromatin-associated Ran-GTP on
      the activities of spindle assembly factors. In this study we show that Mars, a
      Drosophila protein with sequence similarity to vertebrate hepatoma upregulated
      protein (HURP), is required for the attachment of the centrosome to the mitotic
      spindle. More than 80% of embryos derived from mars mutant females do not develop
      properly due to severe mitotic defects during the rapid nuclear divisions in
      early embryogenesis. Centrosomes frequently detach from spindles and from the
      nuclear envelope and nucleate astral microtubules in ectopic positions.
      Consistent with its function in spindle organization, Mars localizes to nuclei in
      interphase and associates with the mitotic spindle, in particular with the
      spindle poles, during mitosis. We propose that Mars is an important linker
      between the spindle and the centrosomes that is required for proper spindle
      organization during the rapid mitotic cycles in early embryogenesis.

PMID- 19174465
TI  - Drosophila Past1 is involved in endocytosis and is required for germline
      development and survival of the adult fly.
AB  - Endocytosis, which is a key process in eukaryotic cells, has a central role in
      maintaining cellular homeostasis, nutrient uptake, development and downregulation
      of signal transduction. This complex process depends on several protein-protein
      interactions mediated by specific modules. One such module is the EH domain. The
      EH-domain-containing proteins comprise a family that includes four vertebrate
      members (EHD1-EHD4) and one Drosophila ortholog, Past1. We used Drosophila as a
      model to understand the physiological role of this family of proteins. We
      observed that the two predicted Past1 transcripts are differentially expressed
      both temporally and spatially during the life cycle of the fly. Endogenous Past1
      as well as Past1A and Past1B, expressed from plasmids, were localized mainly to
      the membrane of Drosophila-derived cells. We generated mutants in the Past1 gene
      by excising a P-element inserted in it. The Past1 mutants reached adulthood but
      died precociously. They were temperature sensitive and infertile because of
      lesions in the reproductive system. Garland cells that originated from Past1
      mutants exhibited a marked decrease in their ability to endocytose fluorescently
      labeled avidin. Genetic interaction was found between Past1 and members of the
      Notch signaling pathway, suggesting a role for Past1 in this developmentally
      crucial signaling pathway.

PMID- 19174466
TI  - Cx43 has distinct mobility within plasma-membrane domains, indicative of
      progressive formation of gap-junction plaques.
AB  - Connexin 43 (Cx43) is a dynamic molecule, having a short half-life of only a few
      hours. In this study, we use fluorescent-protein-tagged Cx43 variants to examine
      Cx43 delivery to the cell surface, its residency status in various cell-surface
      membrane domains and its mobility characteristics. Rapid time-lapse imaging led
      to the identification of Cx43 being delivered to cell-surface domains that lacked
      a contacting cell, and also to its localization within membrane protrusions.
      Fluorescence recovery after photobleaching (FRAP) was used to investigate the
      mobility state of cell-surface-localized Cx43. Cx43 mobility within clustered
      cell-surface profiles of Cx43 could be categorized into those with generally a
      high degree of lateral mobility and those with generally a low degree of lateral
      mobility. Cx43 mobility was independent of cluster size, yet the C-terminal
      domain of Cx43 regulated the proportion of gap-junction-like clusters that
      acquired a low Cx43 mobility state. Collectively, these studies show that Cx43
      establishes residency at all cell-surface membrane domains, and progressively
      acquires assembly states that probably reflect differences in either channel
      packing and/or its interactions with Cx43-binding proteins.

PMID- 19174468
TI  - Functional suppression of E-cadherin by protein kinase Cdelta.
AB  - Protein kinase C (PKC) delta, a member of the novel PKC subfamily, has been shown
      to have an important role in cell proliferation, differentiation, apoptosis and
      cell motility. In this study, we investigated the effect of green fluorescent
      protein (GFP)-PKCdelta and GFP-PKCalpha on cell-cell junctions of Madin-Darby
      canine kidney (MDCK) cells and found that only GFP-PKCdelta suppressed the
      homophilic interactions between the ectodomains of E-cadherins, accompanied by a
      weaker cell-cell adhesion. The kinase-deficient mutant of GFP-PKCdelta retained
      its localization at cell-cell junctions but failed to suppress the function of E
      cadherin. In addition, we demonstrated that the hinge region (residues 280-347)
      that links the regulatory domain and the catalytic domain of PKCdelta is
      essential for both its kinase activity and the targeting of cell-cell junctions.
      A PKCdelta mutant with the deletion of amino acids 280-323 within the hinge
      region, which is catalytically active but defective in the targeting of cell-cell
      junctions, failed to suppress the function of E-cadherin. Moreover, expression of
      GFP-PKCdelta in MDCK cells expedited the detachment of cells from their neighbors
      and facilitated cell scatter induced by hepatocyte growth factor. By contrast,
      the GFP-PKCdelta mutants including the kinase-deficient mutant and the truncated
      mutant lacking residues 280-323 suppressed hepatocyte-growth-factor-induced cell
      scattering. Finally, siRNA-mediated knockdown of endogenous PKCdelta in MDCK
      cells was found to delay the onset of cell-cell detachment and cell scattering
      induced by hepatocyte growth factor. Taken together, our results demonstrate that
      the catalytic activity of PKCdelta and its localization to cell-cell junctions
      are necessary for PKCdelta to suppress the function of E-cadherin, which thereby
      facilitates scattering of epithelial cells in response to extracellular cues.

PMID- 19174467
TI  - Mechanically induced osteogenic differentiation--the role of RhoA, ROCKII and
      cytoskeletal dynamics.
AB  - Many biochemical factors regulating progenitor cell differentiation have been
      examined in detail; however, the role of the local mechanical environment on stem
      cell fate has only recently been investigated. In this study, we examined whether
      oscillatory fluid flow, an exogenous mechanical signal within bone, regulates
      osteogenic, adipogenic or chondrogenic differentiation of C3H10T1/2 murine
      mesenchymal stem cells by measuring Runx2, PPARgamma and SOX9 gene expression,
      respectively. Furthermore, we hypothesized that the small GTPase RhoA and
      isometric tension within the actin cytoskeleton are essential in flow-induced
      differentiation. We found that oscillatory fluid flow induces the upregulation of
      Runx2, Sox9 and PPARgamma, indicating that it has the potential to regulate
      transcription factors involved in multiple unique lineage pathways. Furthermore,
      we demonstrate that the small GTPase RhoA and its effector protein ROCKII
      regulate fluid-flow-induced osteogenic differentiation. Additionally, activated
      RhoA and fluid flow have an additive effect on Runx2 expression. Finally, we show
      RhoA activation and actin tension are negative regulators of both adipogenic and
      chondrogenic differentiation. However, an intact, dynamic actin cytoskeleton
      under tension is necessary for flow-induced gene expression.

PMID- 19174469
TI  - Splicing of HDAC7 modulates the SRF-myocardin complex during stem-cell
      differentiation towards smooth muscle cells.
AB  - Histone deacetylases (HDACs) have a central role in the regulation of gene
      expression. Here we investigated whether HDAC7 has an impact on embryonic stem
      (ES) cell differentiation into smooth muscle cells (SMCs). ES cells were seeded
      on collagen-IV-coated flasks and cultured in the absence of leukemia inhibitory
      factor in differentiation medium to induce SMC differentiation. Western blots and
      double-immunofluorescence staining demonstrated that HDAC7 has a parallel
      expression pattern with SMC marker genes. In ex vivo culture of embryonic cells
      from SM22-LacZ transgenic mice, overexpression of HDAC7 significantly increased
      beta-galactosidase-positive cell numbers and enzyme activity, indicating its
      crucial role in SMC differentiation during embryonic development. We found that
      HDAC7 undergoes alternative splicing during ES cell differentiation. Platelet
      derived growth factor enhanced ES cell differentiation into SMCs through
      upregulation of HDAC7 splicing. Further experiments revealed that HDAC7 splicing
      induced SMC differentiation through modulation of the SRF-myocardin complex.
      These findings suggest that HDAC7 splicing is important for SMC differentiation
      and vessel formation in embryonic development.

PMID- 19174470
TI  - Sphingosine-1-phosphate receptors stimulate macrophage plasma-membrane actin
      assembly via ADP release, ATP synthesis and P2X7R activation.
AB  - Eukaryotic plasma membranes assemble actin filaments within seconds of activation
      of many receptors, especially during chemotaxis. Here, serum or sphingosine-1
      phosphate stimulation of J774 and RAW macrophages released ADP within seconds
      into the extracellular medium, along with an adenylate kinase activity that
      converted ADP to ATP. ATP then activated the P2X7 receptor (P2X7R) that was
      necessary for a peak of plasma-membrane actin assembly within 5 to 10 seconds in
      P2X7R-expressing J774, RAW and primary macrophages. Neither actin assembly nor
      characteristic P2X7R channel activity was seen in response to ATP in P2X7R
      knockout macrophages, as detected by patch-clamp analysis. Since P2X7R has been
      shown previously to form a macromolecular complex with actin we propose that it
      is involved in the membrane assembly of actin. Our data reveal a surprisingly
      rapid and complex relay of signaling and externalization events that precede and
      control actin assembly induced by sphingosine-1-phosphate. The overall model we
      present is strongly supported by the data presented in the accompanying paper
      that focuses on latex bead phagosomes.

PMID- 19174471
TI  - Lipids regulate P2X7-receptor-dependent actin assembly by phagosomes via ADP
      translocation and ATP synthesis in the phagosome lumen.
AB  - Latex bead phagosomes isolated from J774 macrophages polymerize actin. We show
      here that five lipids--phosphatidylinositol-4-phosphate, phosphatidylinositol
      (4,5)-bisphosphate, sphingosine-1-phosphate (S1P), ceramide-1-phosphate and
      phosphatidic acid--stimulate both actin assembly and transport of ADP across the
      phagosomal membrane into the lumen. Once there, this ADP is converted to ATP by
      adenylate kinase activity. High luminal ATP concentrations correlated well with
      phagosome actin assembly under different conditions. The ATP-binding P2X7
      receptor (P2X7R) was detected in phagosomes. Although S1P stimulated actin
      assembly by phagosomes from P2X7R-containing bone marrow macrophages, S1P
      stimulated actin assembly was inhibited in phagosomes from cells lacking P2X7R.
      We propose that luminal ATP accumulates in response to selected lipids and
      activates the P2X7R that signals across the phagosomal membrane to trigger actin
      assembly on the cytoplasmic membrane surface. In the accompanying paper by
      Kuehnel et al. (doi:10.1242/jcs.034207), more evidence is provided in support of
      this model from the analysis of actin assembly at the plasma membrane of intact
      macrophages.

PMID- 19174472
TI  - Drebrin A regulates dendritic spine plasticity and synaptic function in mature
      cultured hippocampal neurons.
AB  - Drebrin A, one of the most abundant neuron-specific F-actin-binding proteins, is
      found exclusively in dendrites and is particularly concentrated in dendritic
      spines receiving excitatory inputs. We investigated the role of drebrin A in
      synaptic transmission and found that overexpression of drebrin A augmented the
      glutamatergic synaptic transmission, probably through an increase of active
      synaptic site density. Interestingly, overexpression of drebrin A also affected
      the frequency, amplitude and kinetics of miniature inhibitory postsynaptic
      currents (mIPSCs), despite the fact that GABAergic synapse density and
      transmission efficacy were not modified. Downregulation of drebrin A led to a
      decrease of both glutamatergic and GABAergic synaptic activity. In heterologous
      cells, drebrin A reorganized and stabilized F-actin and these effects were
      mediated by its actin-binding domain. Thus, drebrin A might regulate dendritic
      spine morphology via regulation of actin cytoskeleton remodeling and dynamics.
      Our data demonstrate for the first time that drebrin A modulates glutamatergic
      and GABAergic synaptic activities.

PMID- 19174473
TI  - GM-CSF-induced CD11c+CD8a--dendritic cells facilitate Foxp3+ and IL-10+
      regulatory T cell expansion resulting in suppression of autoimmune thyroiditis.
AB  - GM-CSF plays an essential role in the differentiation of dendritic cells (DCs).
      Our studies have shown that GM-CSF treatment can induce semi-mature DCs and
      CD4+CD25+ regulatory T cells (Tregs) and suppress ongoing autoimmunity in mouse
      models. In this study, we examined the differences in the potential of GM-CSF to
      exert tolerogenic function on CD8a+ and CD8a- sub-populations of DCs in vivo. We
      show that GM-CSF modulates CD8a-, but not CD8a+ DCs in vivo, by inhibiting the
      surface expression of activation markers MHC II and CD80 and production of
      inflammatory cytokines such as IL-12 and IL-1beta. Self-antigen [mouse
      thyroglobulin (mTg)] presentation by GM-CSF-exposed CD8a- DCs to T cells from mTg
      primed mice induced a profound increase in the frequency of forkhead box P3
      (FoxP3)-expressing T cells compared with antigen presentation by GM-CSF-exposed
      CD8a+ DCs and control CD8a+ and CD8a- DCs. This tolerogenic property of GM-CD8a-
      DCs was abrogated when IL-12 was added. GM-CSF-exposed CD8a- DCs could also
      induce secretion of significantly higher amounts of IL-10 by T cells from mTg
      primed mice. Importantly, adoptive transfer of CD8a- DCs from GM-CSF-treated SCID
      mice, but not untreated mice, into wild-type CBA/J mice prevented the development
      of experimental autoimmune thyroiditis (EAT) in the recipient animals upon
      immunization with mTg. Collectively, our results show that GM-CSF renders CD8a-
      DCs tolerogenic, and these DCs induce Foxp3+ and IL-10+ Tregs.

PMID- 19174474
TI  - A novel adjuvant, the general opioid antagonist naloxone, elicits a robust
      cellular immune response for a DNA vaccine.
AB  - While many adjuvants have been discovered and used in research, only a few
      adjuvants have been permitted for use with human vaccination. We have previously
      shown that the administration of naloxone (NLX), a general opioid antagonist,
      during infection with a non-virulent strain of herpes simplex virus type 1 (HSV
      1) could enhance protection against HSV-1 challenge. Here, the adjuvant activity
      of NLX has been evaluated using a DNA vaccine for HSV-1 as a model. BALB/c mice
      were divided into four groups; for experimental groups, mice received the
      glycoprotein D1 (gD1) DNA vaccine alone or in combination with the adjuvant NLX.
      A positive control group received the KOS strain of HSV-1, and a negative control
      group received PBS. All mice were immunized three times on days 0, 21 and 42.
      Three weeks after the last immunization, immune responses against HSV-1 were
      assessed. Our results indicate that the administration of NLX as an adjuvant
      increased the ability of the gD1 DNA vaccine to enhance cytolytic T lymphocyte
      activity, lymphocyte proliferation, delayed-type hypersensitivity and shifting
      the immune response toward a T helper (Th)1 pattern and improved protective
      immunity against HSV-1. NLX also increased the IgG2a/IgG1 ratio, though it did
      not affect the production of HSV-1 antiserum. In conclusion, administration of
      NLX as an adjuvant in combination with the gD1 DNA vaccine can enhance cell
      mediated immunity and shift the immune responses to Th1.

PMID- 19174475
TI  - The mechanism of ABC transporters: general lessons from structural and functional
      studies of an antigenic peptide transporter.
AB  - The shuttling of substrates across a cellular membrane frequently requires a
      specialized ATP-binding cassette (ABC) transporter, which couples the energy of
      ATP binding and hydrolysis to substrate transport. Due to its importance in
      immunity, the ABC transporter associated with antigen processing (TAP) has been
      studied extensively and is an excellent model for other ABC transporters. The TAP
      protein pumps cytosolic peptides into the endoplasmic reticulum for loading onto
      class I major histocompatibility complex (MHC) for subsequent immune
      surveillance. Here, we outline a potential mechanism for the TAP protein with
      supporting evidence from bacterial transporter structures. The similarities and
      differences between TAP and other transporters support the notion that ABC
      transporters in general have adapted around a universal transport mechanism.

PMID- 19174476
TI  - Discovery of the gene signature for acute lung injury in patients with sepsis.
AB  - The acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) was
      described 30 yr ago, yet making a definitive diagnosis remains difficult. The
      identification of biomarkers obtained from peripheral blood could provide
      additional noninvasive means for diagnosis. To identify gene expression profiles
      that may be used to classify patients with ALI, 13 patients with ALI + sepsis and
      20 patients with sepsis alone were recruited from the Medical Intensive Care Unit
      of the University of Pittsburgh Medical Center, and microarrays were performed on
      peripheral blood samples. Several classification algorithms were used to develop
      a gene signature for ALI from gene expression profiles. This signature was
      validated in an independently obtained set of patients with ALI + sepsis (n = 8)
      and sepsis alone (n = 1). An eight-gene expression profile was found to be
      associated with ALI. Internal validation found that the gene signature was able
      to distinguish patients with ALI + sepsis from patients with sepsis alone with
      100% accuracy, corresponding to a sensitivity of 100%, a specificity of 100%, a
      positive predictive value of 100%, and a negative predictive value of 100%. In
      the independently obtained external validation set, the gene signature was able
      to distinguish patients with ALI + sepsis from patients with sepsis alone with
      88.9% accuracy. The use of classification models to develop a gene signature from
      gene expression profiles provides a novel and accurate approach for classifying
      patients with ALI.

PMID- 19174477
TI  - Paternal deletion of Meg1/Grb10 DMR causes maternalization of the Meg1/Grb10
      cluster in mouse proximal Chromosome 11 leading to severe pre- and postnatal
      growth retardation.
AB  - Mice with maternal duplication of proximal Chromosome 11 (MatDp(prox11)), where
      Meg1/Grb10 is located, exhibit pre- and postnatal growth retardation. To
      elucidate the responsible imprinted gene for the growth abnormality, we examined
      the precise structure and regulatory mechanism of this imprinted region and
      generated novel model mice mimicking the pattern of imprinted gene expression
      observed in the MatDp(prox11) by deleting differentially methylated region of
      Meg1/Grb10 (Meg1-DMR). It was found that Cobl and Ddc, the neighboring genes of
      Meg1/Grb10, also comprise the imprinted region. We also found that the mouse
      specific repeat sequence consisting of several CTCF-binding motifs in the Meg1
      DMR functions as a silencer, suggesting that the Meg1/Grb10 imprinted region
      adopted a different regulatory mechanism from the H19/Igf2 region. Paternal
      deletion of the Meg1-DMR (+/DeltaDMR) caused both upregulation of the maternally
      expressed Meg1/Grb10 Type I in the whole body and Cobl in the yolk sac and loss
      of paternally expressed Meg1/Grb10 Type II and Ddc in the neonatal brain and
      heart, respectively, demonstrating maternalization of the entire Meg1/Grb10
      imprinted region. We confirmed that the +/DeltaDMR mice exhibited the same growth
      abnormalities as the MatDp(prox11) mice. Fetal and neonatal growth was very
      sensitive to the expression level of Meg1/Grb10 Type I, indicating that the 2
      fold increment of the Meg1/Grb10 Type I is one of the major causes of the growth
      retardation observed in the MatDp(prox11) and +/DeltaDMR mice. This suggests that
      the corresponding human GRB10 Type I plays an important role in the etiology of
      Silver-Russell syndrome caused by partial trisomy of 7p11-p13.

PMID- 19174478
TI  - MeCP2 involvement in the regulation of neuronal alpha-tubulin production.
AB  - Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by a dominant
      mutation in the X-linked methyl CpG binding protein 2 (MeCP2) gene.
      Neuroanatomically, RTT is characterized by a reduction in dendritic arborization
      and perikaryal size in the brain. MECP2 binds methylated promoters and
      facilitates assembly of a multiprotein repressor complex that includes Sin3A and
      the histone deacetylases HDAC1/HDAC2. MeCP2 has recently been found to be
      downregulated in autistic spectrum disorders such as Angelman syndrome (AS) and
      RTT, which share some phenotypic manifestations. We have conducted expression
      analysis of cytoskeleton-related genes in brain tissue of RTT and AS patients.
      Striking examples of genes with reduced expression were TUBA1B and TUBA3 that
      encode the ubiquitous alpha-tubulin and the neuronal specific alpha-tubulin,
      respectively. In accordance with the downregulation of expression of these genes,
      we have observed a reduction in the level of the corresponding protein product
      tyrosinated alpha-tubulin. Low levels of alpha-tubulin and deteriorated cell
      morphology were also observed in MeCP2(-/y) MEF cells. The effects of MeCP2
      deficiency in these cells were completely reversed by introducing and expressing
      the human MeCP2 gene. These results imply that MeCP2 is involved in the
      regulation of neuronal alpha-tubulin and add molecular evidence that reversal of
      the effects of MeCP2 deficiency is achievable. This raises hopes for a cure of
      Rett syndrome and related MeCP2 deficiency disorders of the autistic spectrum.

PMID- 19174479
TI  - Gene expression divergence and hybrid misexpression between lake whitefish
      species pairs (Coregonus spp. Salmonidae).
AB  - Genomewide analyses of the transcriptome have confirmed that gene misexpression
      may underlie reproductive isolation mechanisms in interspecific hybrids. Here,
      using a 16,006 features cDNA microarray, we compared and contrasted gene
      expression divergence at two ontogenetic stages in incipient species of normal
      and dwarf whitefish (Coregonus clupeaformis) with that of first generation
      (normal x dwarf) and second-generation hybrid crosses (backcross: [normal x
      dwarf] x normal]. Our goal was to identify the main mode of action responsible
      for gene transcription and to discover key genes misexpressed in hybrids. Very
      few transcripts (five of 4,950 expressed) differed in mean expression level
      between parentals and hybrids at the embryonic stage, in contrast to 16-week-old
      juvenile fish for which 617 out of 5,359 transcripts differed significantly. We
      also found evidence for more misexpression in backcross hybrids whereby
      nonadditivity explained a larger fraction of hybrid inheritance patterns in
      backcross (54%) compared with F1-hybrids (9%). Gene expression in hybrids was
      more variable than in pure crosses and transgressive patterns of expression were
      ubiquitous in hybrids. In backcross embryos in particular, the expression of
      three key developmental genes involved in protein folding and mRNA translation
      was severely disrupted. Accordingly, gene misexpression in hybrids adds to other
      factors previously identified as contributing to the reproductive isolation of
      incipient species of lake whitefish.

PMID- 19174480
TI  - The endothelin system: evolution of vertebrate-specific ligand-receptor
      interactions by three rounds of genome duplication.
AB  - Morphological innovations like the acquisition of the neural crest as well as
      gene family expansions by genome duplication are considered as major leaps in the
      evolution of the vertebrate lineage. Using comparative genomic analyses, we have
      reconstructed the evolutionary history of the endothelin system, a signaling
      pathway consisting of endothelin ligands and their G protein-coupled receptors.
      The endothelin system plays a key role in cardiovascular regulation as well as in
      the development of diverse neural crest derivatives like pigment cells and
      craniofacial bone structures, which are hot spots of diversity in vertebrates.
      However, little is known about the origin and evolution of the endothelin system
      in the vertebrate lineage. We show that the endothelin core system, that is,
      endothelin ligands (Edn) and their receptors (Ednr), is a vertebrate-specific
      innovation. The components of the endothelin core system in modern vertebrate
      genomes date back to single genes that have been duplicated during whole-genome
      duplication events. After two rounds of genome duplication during early
      vertebrate evolution, the endothelin system of an ancestral gnathostome consisted
      of four ligand and four receptor genes. The previously unknown fourth endothelin
      ligand Edn4 has been kept in teleost fish but lost in tetrapods. Bony vertebrates
      generally possess three receptor genes, EdnrA, EdnrB1, and EdnrB2. EdnrB2 has
      been lost secondarily in the mammalian lineage from a chromosome that gave rise
      to the sex chromosomes in therians (marsupials and placentals). The endothelin
      system of fishes was further expanded by a fish-specific genome duplication and
      duplicated edn2, edn3, ednrA, and ednrB1 genes have been retained in teleost
      fishes. Functional divergence analyses suppose that following each round of
      genome duplication, coevolution of ligands and their binding regions in the
      receptors has occurred, adjusting the endothelin signaling system to the increase
      of possible ligand-receptor interactions. Furthermore, duplications of genes
      involved in the endothelin system are associated with functional specialization
      for the development of particular neural crest derivatives. Our results support
      an important role for newly emerging ligands and receptors as components of
      signaling pathways and their expansion through genome duplications in the
      evolution of the vertebrate neural crest.

PMID- 19174481
TI  - Genomic and proteomic analyses reveal non-neofunctionalized vitellogenins in a
      basal clupeocephalan, the Atlantic herring, and point to the origin of
      maturational yolk proteolysis in marine teleosts.
AB  - Oocyte hydration is a unique event in oviparous marine teleosts that provides the
      single-celled egg with an essential pool of water for survival during early
      development in the saline oceanic environment. A conserved mechanism of
      maturational yolk proteolysis of a neofunctionalized vitellogenin (VtgAa) has
      been shown to underlie the hydration event in all teleosts that spawn pelagic
      eggs (pelagophils), and is argued to be a key adaptation for teleost radiation in
      the oceanic environment 55 Ma. We have recently shown that a small pool of free
      amino acids (FAAs) significantly contributes to the osmolarity of the ovulated
      egg in an ancestral marine teleost, the Atlantic herring that spawns benthic eggs
      (benthophil). To determine whether multiple forms of vtg exist and whether
      neofunctionalization of the gene products are related to the egg FAA pool in this
      species, genomic sequences conserved between the exons of Atlantic herring and
      zebrafish were amplified. This approach identified a small polymorphic intron
      between exons 9 and 10 in Atlantic herring and demonstrated that two closely
      related major vtg transcripts (chvtgAc1 and chvtgAc2) are expressed during
      oogenesis. A separate polymerase chain reaction-based approach identified a more
      ancestral phosvitinless transcript (chvtgC). Proteomic analyses of the translated
      products of the major vtg forms demonstrated that the yolk proteins are similarly
      processed during deposition, and oocyte maturation and reveal that vtgs have
      duplicated but not neofunctionalized in this species. Phylogenetic analyses
      consistently clustered the transcripts and proteins as the basal sister group to
      the Ostariophysi in full congruence with the Clupeocephalan rank, and suggest
      that expansion of ostariophysan vtgAo1 and vtgAo2 genes occurred in a lineage
      specific manner after separation from the Clupeiformes. Three-dimensional
      modeling of the ChvtgAc1 sequence against the resolved lamprey lipovitellin
      module revealed that the tertiary structure is highly conserved, with most
      substitutions occurring on the outside of the molecule. The data indicate that
      the phosvitin domain, the smallest yet reported for teleosts, and an N-terminal
      fragment of the lipovitellin light chain contribute to the FAA pool. The present
      findings thus show that yolk proteolysis and the generation of an organic
      osmolyte pool of FAAs was an adaptive response to spawning in seawater also for
      the Clupeiformes, but that this process was not evolutionarily successful in
      terms of biodiversity until vtg gene neofunctionalization occurred in the
      Acanthomorpha.

PMID- 19174483
TI  - Multimodel inference and multimodel averaging in empirical modeling of
      occupational exposure levels.
AB  - Empirical modeling of exposure levels has been popular for identifying exposure
      determinants in occupational hygiene. Traditional data-driven methods used to
      choose a model on which to base inferences have typically not accounted for the
      uncertainty linked to the process of selecting the final model. Several new
      approaches propose making statistical inferences from a set of plausible models
      rather than from a single model regarded as 'best'. This paper introduces the
      multimodel averaging approach described in the monograph by Burnham and Anderson.
      In their approach, a set of plausible models are defined a priori by taking into
      account the sample size and previous knowledge of variables influent on exposure
      levels. The Akaike information criterion is then calculated to evaluate the
      relative support of the data for each model, expressed as Akaike weight, to be
      interpreted as the probability of the model being the best approximating model
      given the model set. The model weights can then be used to rank models, quantify
      the evidence favoring one over another, perform multimodel prediction, estimate
      the relative influence of the potential predictors and estimate multimodel
      averaged effects of determinants. The whole approach is illustrated with the
      analysis of a data set of 1500 volatile organic compound exposure levels
      collected by the Institute for work and health (Lausanne, Switzerland) over 20
      years, each concentration having been divided by the relevant Swiss occupational
      exposure limit and log-transformed before analysis. Multimodel inference
      represents a promising procedure for modeling exposure levels that incorporates
      the notion that several models can be supported by the data and permits to
      evaluate to a certain extent model selection uncertainty, which is seldom
      mentioned in current practice.

PMID- 19174482
TI  - New superfamilies of eukaryotic DNA transposons and their internal divisions.
AB  - Despite their enormous diversity and abundance, all currently known eukaryotic
      DNA transposons belong to only 15 superfamilies. Here, we report two new
      superfamilies of DNA transposons, named Sola and Zator. Sola transposons encode
      DDD-transposases (transposase, TPase) and are flanked by 4-bp target site
      duplications (TSD). Elements from the Sola superfamily are distributed in a
      variety of species including bacteria, protists, plants, and metazoans. They can
      be divided into three distinct groups of elements named Sola1, Sola2, and Sola3.
      The elements from each group have extremely low sequence identity to each other,
      different termini, and different target site preferences. However, all three
      groups belong to a single superfamily based on significant PSI-Blast identities
      between their TPases. The DDD TPase sequences encoded by Sola transposons are not
      similar to any known TPases. The second superfamily named Zator is characterized
      by 3-bp TSD. The Zator superfamily is relatively rare in eukaryotic species, and
      it evolved from a bacterial transposon encoding a TPase belonging to the
      "transposase 36" family (Pfam07592). These transposons are named TP36 elements
      (abbreviated from transposase 36).

PMID- 19174484
TI  - Comments on Asbestos fibre concentrations in the lungs of brake workers: another
      look.

PMID- 19174485
TI  - Formaldehyde risk assessment.

PMID- 19174486
TI  - New respirator fit test panels representing the current Chinese civilian workers.
AB  - Respirator fit test panels provide an objective tool for selecting representative
      human test subjects based upon their facial characteristics for use in research,
      product development, testing and certification. Fit test panels were typically
      based upon anthropometric data such as the 1967-1968 survey of American military
      personnel. In this study, the objectives were to: (i) evaluate the applicability
      of the recently developed National Institute for Occupational Safety and Health
      (NIOSH) respirator fit test panels for Chinese workers and (ii) develop new
      respirator fit test panels using the Chinese survey data. Overall, 95% of the
      workers in the Chinese survey fall within the NIOSH bivariate and principal
      component analysis (PCA) panels, suggesting that these panels would also be
      appropriate for the Chinese population. However, distribution of the subject
      across the panels was not uniform; only 6.3% of survey participants fell into
      five cells of the bivariate panel and only 7.2% were found within three cells of
      the PCA panel. Therefore, new respirator fit test panels with subject dimensions
      and distributions specific to Chinese workers may be beneficial for certain
      applications. Two new respirator fit test panels were developed with the same
      techniques used to create the NIOSH panels. All measurements were weighted to
      match age and gender distributions of the Chinese population from the 2005
      census. The bivariate approach used face length and face width measurements, and
      the PCA panel was developed using the first two principal components obtained
      from a set of 10 facial dimensions. Respirators designed to fit these Chinese
      worker-specific panels are also likely to accommodate >95% of Chinese workers.

PMID- 19174487
TI  - Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan
      activity against childhood neuroblastoma.
AB  - PURPOSE: High-risk neuroblastoma is characterized by poor survival rates, and the
      development of improved therapeutic approaches is a priority. Temozolomide and
      topotecan show promising clinical activity against neuroblastoma. Poly(ADP
      ribose) polymerase-1 (PARP-1) promotes DNA repair and cell survival following
      genotoxic insult; we postulated that its inhibition may enhance the efficacy of
      these DNA-damaging drugs in pediatric cancers. EXPERIMENTAL DESIGN: We evaluated
      the chemosensitizing properties of the PARP inhibitor AG014699 (Pfizer, Inc.) in
      combination with temozolomide and topotecan, against human neuroblastoma cells
      and xenografts, alongside associated pharmacologic and toxicologic indices.
      RESULTS: Addition of PARP-inhibitory concentrations of AG014699 significantly
      potentiated growth inhibition by both topotecan (1.5- to 2.3-fold) and
      temozolomide (3- to 10-fold) in vitro, with equivalent effects confirmed in
      clonogenic assays. In two independent in vivo models (NB1691 and SHSY5Y
      xenografts), temozolomide caused a xenograft growth delay, which was enhanced by
      co-administration of AG014699, and resulted in complete and sustained tumor
      regression in the majority (6 of 10; 60%) of cases. Evidence of enhanced growth
      delay by topotecan/AG014699 co-administration was observed in NB1691 xenografts.
      AG014699 metabolites distributed rapidly into the plasma (Cmax, 1.2-1.9 nmol/L at
      30 min) and accumulated in xenograft tissues (Cmax, 1-2 micromol/L at 120 min),
      associated with a sustained suppression of PARP-1 enzyme activity. Doses of
      AG014699 required for potentiation were not toxic per se. CONCLUSIONS: These data
      show enhancement of temozolomide and topotecan efficacy by PARP inhibition in
      neuroblastoma. Coupled with the acceptable pharmacokinetic, pharmacodynamic, and
      toxicity profiles of AG014699, our findings provide strong rationale for
      investigation of PARP inhibitors in pediatric early clinical studies.

PMID- 19174488
TI  - Retinoblastoma tumor suppressor gene expression determines the response to
      sequential flavopiridol and doxorubicin treatment in small-cell lung carcinoma.
AB  - PURPOSE: Small-cell lung cancers (SCLC) are defective in many regulatory
      mechanisms that control cell cycle progression, i.e., functional retinoblastoma
      protein (pRb). Flavopiridol inhibits proliferation and induces apoptosis in SCLC
      cell lines. We hypothesized that the sequence flavopiridol followed by
      doxorubicin would be synergistic in pRb-deficient SCLC cells. EXPERIMENTAL
      DESIGN: A H69 pRb-deficient SCLC cell line, H865, with functional pRb and H865
      pRb small interfering RNA (siRNA) knockdown cells were used for in vitro and in
      vivo experiments. The in vivo efficiencies of various sequential combinations
      were tested using nude/nude athymic mice and human SCLC xenograft models.
      RESULTS: Flavopiridol then doxorubicin sequential treatment was synergistic in
      the pRB-negative H69 cell line. By knocking down pRb with specific siRNA, H865
      clones with complete pRb knockdown became sensitive to flavopiridol and
      doxorubicin combinations. pRb-deficient SCLC cell lines were highly sensitive to
      flavopiridol-induced apoptosis. pRb-positive H865 cells arrested in G0-G1 with
      flavopiridol exposure, whereas doxorubicin and all flavopiridol/doxorubicin
      combinations caused a G2-M block. In contrast, pRb-negative SCLC cells did not
      arrest in G0-G1 with flavopiridol exposure. Flavopiridol treatment alone did not
      have an in vivo antitumor effect, but sequential flavopiridol followed by
      doxorubicin treatment provided tumor growth control and a survival advantage in
      Rb-negative xenograft models, compared with the other sequential treatments.
      CONCLUSIONS: Flavopiridol and doxorubicin sequential treatment induces potent in
      vitro and in vivo synergism in pRb-negative SCLC cells and should be clinically
      tested in tumors lacking functional pRB.

PMID- 19174489
TI  - Osteopontin levels in an asbestos-exposed population.
AB  - PURPOSE: Serum osteopontin levels in patients with malignant mesothelioma have
      been reported to be higher than in healthy subjects. This study assessed serum
      osteopontin levels in an asbestos-exposed population to test whether nonmalignant
      asbestos-related disorders could influence osteopontin levels. EXPERIMENTAL
      DESIGN: This cross-sectional study evaluated serum osteopontin levels in 525 male
      subjects. Subjects were classified into six different diagnostic groups,
      including asbestosis (n=23), silicosis (n=20), diffuse pleural thickening
      (n=110), asbestosis and diffuse pleural thickening (n=13), pleural plaques
      (n=142), and healthy subjects with a history of asbestos exposure (n=217).
      RESULTS: Mean serum osteopontin levels differed among the six groups (P<0.0001).
      Mean osteopontin values of the healthy individuals exposed to asbestos were
      significantly different from that of subjects with asbestosis (P<0.001) and
      diffuse pleural thickening (P<0.001). There was a significant difference in mean
      serum levels of osteopontin in healthy individuals exposed to asbestos (n=217)
      compared with the group mean of all subjects with asbestos-related disorders
      (n=288; P<0.0001). CONCLUSIONS: Our results suggest that osteopontin levels are
      elevated in subjects with asbestos-related disorders without malignant
      mesothelioma. These data indicate that osteopontin, although reported to be
      useful for detecting malignant mesothelioma in asbestos-exposed individuals, may
      be influenced by nonmalignant processes.

PMID- 19174490
TI  - Tobacco and estrogen metabolic polymorphisms and risk of non-small cell lung
      cancer in women.
AB  - To explore the potential role for estrogen in lung cancer susceptibility,
      candidate single-nucleotide polymorphism (SNPs) in tobacco and estrogen
      metabolism genes were evaluated. Population-based cases (n = 504) included women
      aged 18-74, diagnosed with NSCLC in metropolitan Detroit between November 2001
      and October 2005. Population-based controls (n = 527) were identified through
      random digit dialing and matched on race and age. Eleven SNPs in 10 different
      genes were examined in relation to risk: CYP1A1 Msp1, CYP1A1 Ile462Val, CYP1B1
      Leu432Val, CYP17, CYP19A1, XRCC1 Gln399Arg, COMT Val158Met, NQO1 Pro187Ser,
      GSTM1, GSTT1 and GSTP1 Ile105Val. Lung cancer risk associated with individual
      SNPs was seen for GSTP1 [A allele; odds ratio (OR) = 1.85; 95% confidence
      interval (CI), 1.04-3.27] and XRCC1 (A/A genotype; OR = 1.68; 95% CI, 1.01-2.79)
      in white women and CYP1B1 (G allele; OR = 11.1; 95% CI, 1.18-104) in black women
      smokers. White women smokers carrying two risk genotypes at the following loci
      were at increased risk of lung cancer compared with individuals not carrying risk
      alleles at these loci: CYP17 and GSTM1, COMT and GSTM1, CYP17 and GSTT1, XRCC1
      and GSTP1, CYP1B1 and XRCC1 and COMT and XRCC1. The most parsimonious model of
      lung cancer risk in white smoking women included age, family history of lung
      cancer, history of chronic lung disease, pack-years, body mass index, XRCC1 A/A
      genotype, GSTM1 null and COMT A/G or G/G genotype. These findings support the
      need for continued study of estrogen in relation to lung cancer risk.
      Polymorphisms in the tobacco metabolism, estrogen metabolism and DNA repair
      pathways will be useful in developing more predictive models of individual risk.

PMID- 19174491
TI  - Increased hypothalamic-pituitary-adrenal axis activity in Huntington's disease.
AB  - CONTEXT: Huntington's disease (HD) is a fatal hereditary neurodegenerative
      disorder characterized by motor, cognitive, and behavioral disturbances.
      Hypothalamic-pituitary-adrenal (HPA) axis dysfunction could contribute to a
      number of HD signs and symptoms; however, no data are available on cortisol
      diurnal variations and secretory dynamics in HD patients. OBJECTIVE: The aim of
      the study was to perform a detailed analysis of HPA axis function in HD patients
      in relation to clinical signs and symptoms. DESIGN, SETTING, AND PARTICIPANTS:
      Twenty-four-hour cortisol secretion was studied in eight early-stage, medication
      free HD patients and eight age-, sex-, and body mass index-matched controls in a
      clinical research laboratory. Cortisol levels were measured every 10 min. MAIN
      OUTCOME MEASURES: Multiparameter autodeconvolution and cosinor regression were
      applied to quantify basal, pulsatile, and total cortisol secretion rates as well
      as diurnal variations in cortisol levels. RESULTS: Total cortisol secretion rate
      and the amplitude of the diurnal cortisol profile were both significantly higher
      in HD patients compared with controls (3490 +/- 320 vs. 2500 +/- 220
      nmol/liter/24 h, P = 0.023; and 111 +/- 14 vs. 64 +/- 8 nmol/liter, P = 0.012,
      respectively). Cortisol concentrations in patients were particularly increased in
      the morning and early afternoon period. In HD patients, mean 24-h cortisol levels
      significantly correlated with total motor score, total functional capacity, as
      well as body mass index. CONCLUSIONS: HPA axis hyperactivity is an early feature
      of HD and is likely to result from a disturbed central glucocorticoid feedback
      due to hypothalamic pathology. HPA axis dysfunction may contribute to some signs
      and symptoms in HD patients.

PMID- 19174492
TI  - Vitamin D deficiency in older men.
AB  - CONTEXT: Vitamin D deficiency is not adequately evaluated in older men.
      OBJECTIVE: The aim of the study was to determine the prevalence of vitamin D
      deficiency and identify risk factors for its occurrence. DESIGN AND SETTING: We
      conducted a cross-sectional evaluation of 1606 older men in the general community
      who were enrolled in the Osteoporotic Fractures in Men Study. PARTICIPANTS: A
      randomly selected subcohort of a large population of men from six U.S.
      communities participated in the study. MAIN OUTCOME MEASURES: Serum
      concentrations of 25-hydroxyvitamin D(2) [25(OH)D(2)] and 25(OH)D(3) were
      measured using mass spectrometry. RESULTS: Deficiency [25(OH)D <20 ng/ml] was
      present in 26%, and insufficiency (<30 ng/ml) was present in 72%. Deficiency was
      particularly common among men during the winter and spring (especially in the
      northern communities) and in the oldest and more obese men. For instance, in
      Caucasian men in winter or spring who were >80 yr old, did not engage in
      lawn/garden work, and had a body mass index greater than 25 kg/m(2) and vitamin D
      intake below 400 IU/d, the prevalence of vitamin D deficiency was 86%. 25(OH)D(2)
      levels were present in a small fraction of men and accounted for a low proportion
      of total 25(OH)D levels. The use of vitamin D supplements was reported by 58% of
      men, but supplement use had a small effect on total 25(OH)D levels and, despite
      supplement use, low levels remained frequent. CONCLUSIONS: Vitamin D deficiency
      is common in older men and is especially prevalent in obese, sedentary men living
      at higher latitudes. Use of vitamin D supplements at levels reported here did not
      result in adequate vitamin D nutrition.

PMID- 19174493
TI  - Effects of an oral growth hormone secretagogue in older adults.
AB  - CONTEXT: GH secretion declines with age, possibly contributing to reduced muscle
      mass, strength, and function. GH secretagogues (GHS) may increase muscle mass and
      physical performance. OBJECTIVES/DESIGN: We conducted a randomized, double
      masked, placebo-controlled, multicenter study to investigate the hormonal, body
      composition, and physical performance effects and the safety of the orally active
      GHS capromorelin in older adults with mild functional limitation.
      INTERVENTION/PARTICIPANTS: A total of 395 men and women aged 65-84 yr were
      randomized for an intended 2 yr of treatment to four dosing groups (10 mg three
      times/week, 3 mg twice a day, 10 mg each night, and 10 mg twice a day) or
      placebo. Although the study was terminated early according to predetermined
      treatment effect criteria, 315 subjects completed 6 months of treatment, and 284
      completed 12 months. RESULTS: A sustained dose-related rise in IGF-I
      concentrations occurred in all active treatment groups. Each capromorelin dose
      prompted a rise in peak nocturnal GH, which was greatest with the least frequent
      dosing. At 6 months, body weight increased 1.4 kg in subjects receiving
      capromorelin and decreased 0.2 kg in those receiving placebo (P = 0.006). Lean
      body mass increased 1.4 vs. 0.3 kg (P = 0.001), and tandem walk improved by 0.9
      sec (P = 0.02) in the pooled treatment vs. placebo groups. By 12 months, stair
      climb also improved (P = 0.04). Adverse events included fatigue, insomnia, and
      small increases in fasting glucose, glycosylated hemoglobin, and indices of
      insulin resistance. CONCLUSIONS: In healthy older adults at risk for functional
      decline, administration of the oral GHS capromorelin may improve body composition
      and physical function.

PMID- 19174494
TI  - Decreased bone turnover despite persistent secondary hyperparathyroidism during
      prolonged treatment with imatinib.
AB  - CONTEXT: The tyrosine kinase inhibitor imatinib mesylate has an established role
      in the management of a number of malignant and proliferative conditions. Cross
      sectional and short-term prospective studies have demonstrated secondary
      hyperparathyroidism during imatinib therapy, and variable changes in markers of
      bone turnover. OBJECTIVE: Our objective was to determine the biochemical and
      skeletal effects of imatinib during long-term therapy. DESIGN: This was a 2-yr
      prospective study. SETTING: The study was performed at an academic clinical
      research center. PATIENTS OR OTHER PARTICIPANTS: Nine patients with bcr-abl
      positive chronic myeloid leukemia were included in the study. INTERVENTIONS:
      Patients received Imatinib mesylate 400 mg/d. MAIN OUTCOME MEASURES: Serum and
      urine biochemistry, markers of bone turnover, and bone mineral density were
      measured. RESULTS: Participants developed mild secondary hyperparathyroidism,
      with significant decreases in serum calcium and phosphate (P < 0.05 and P <
      0.0001 vs. baseline, respectively) and an increase in PTH (P < 0.0001 vs.
      baseline). Biochemical markers of bone turnover demonstrated a biphasic response,
      with an initial increase in markers of bone formation being followed by a
      decrease in markers of both formation and resorption. Bone density at the lumbar
      spine increased [mean (95% confidence interval) change from baseline 3.6% (1.6,
      5.5); P = 0.003] as did that at the total body [1.4% (0.2, 2.5); P = 0.065],
      whereas that at the proximal femur did not change [-0.12% (-3.0, 2.7); P = 0.93].
      Body weight and fat mass increased significantly (P < 0.0001 vs. baseline).
      CONCLUSIONS: Long-term treatment with imatinib leads to persistent mild secondary
      hyperparathyroidism. Despite this, bone turnover is decreased, and bone density
      is stable or increased. Evaluation of the skeletal actions and safety of imatinib
      during longer-term therapy is warranted.

PMID- 19174495
TI  - Hyperglycemia acutely lowers the postprandial excursions of glucagon-like Peptide
      1 and gastric inhibitory polypeptide in humans.
AB  - INTRODUCTION: Impaired secretion of glucagon-like peptide 1 (GLP-1) has been
      suggested to contribute to the deficient incretin effect in patients with type 2
      diabetes. It is unclear whether this is a primary defect or a consequence of the
      hyperglycemia in type 2 diabetes. We examined whether acute hyperglycemia reduces
      the postprandial excursions of gastric inhibitory polypeptide (GIP) and GLP-1,
      and if so, whether this can be attributed to changes in gastric emptying.
      PATIENTS AND METHODS: Fifteen nondiabetic individuals participated in a
      euglycemic clamp and a hyperglycemic clamp experiment, carried out over 285 min.
      A mixed meal was ingested after 45 min. Plasma concentrations of glucose,
      insulin, C-peptide, glucagon, triglycerides, GIP, and GLP-1 were determined, and
      gastric emptying was assessed using a (13)C-octanoate breath test. RESULTS:
      Glucose levels were 160 +/- 1 mg/dl during the hyperglycemic clamp experiments
      and 83 +/- 3 mg/dl during the euglycemia (P < 0.0001). Glucose infusion rates
      were higher during hyperglycemia, but meal ingestion led to a decline in glucose
      requirements in both experiments (P < 0.0001). Insulin and C-peptide levels were
      higher during the hyperglycemic clamp experiments (P < 0.0001), whereas glucagon
      levels were higher during euglycemia (P < 0.0001). The postprandial increases in
      GIP and GLP-1 concentrations were 46 and 52% lower during the experiments with
      hyperglycemia (P = 0.0017 and P = 0.021). Hyperglycemia also elicited a
      significant delay in gastric emptying (P < 0.0001). CONCLUSIONS: Hyperglycemia
      acutely reduces the postprandial levels of GIP and GLP-1, possibly through a
      deceleration of gastric emptying. This supports the concept that reduced incretin
      levels in some patients with type 2 diabetes are a consequence rather than a
      cause of type 2 diabetes.

PMID- 19174496
TI  - In vitro hyperresponsiveness to tumor necrosis factor-alpha contributes to
      adipokine dysregulation in omental adipocytes of obese subjects.
AB  - CONTEXT: In obesity, adipocyte hypertrophy and macrophage infiltration lead to
      overproduction of proinflammatory adipokines, which play a crucial role in the
      metabolic syndrome. The molecular mechanisms underlying this overproduction are
      still unsettled. The role of TNF-alpha also remains controversial in human
      obesity. OBJECTIVE: We revisited the contribution of TNF-alpha to adipokine
      dysregulation in central obesity. We more particularly assessed the involvement
      of TNF-alpha vs. other stromal-vascular cell (SVC)-secreted factors and searched
      for potential differential responses to TNF-alpha between adipocytes of lean and
      obese individuals. DESIGN AND PARTICIPANTS: Primary cultures of omental
      adipocytes from obese and nonobese age- and sex-matched subjects were used. For
      some experiments, we generated media previously conditioned by SVCs, which mimic
      adipocyte microenvironment. RESULTS: Adipocytes of obese subjects mainly
      overexpressed adipokines, in comparison with those of lean ones, when cultured in
      SVC-conditioned media. This was abrogated by immunoneutralization of TNF-alpha,
      indicating that among the numerous factors secreted by SVCs, TNF-alpha is a
      crucial contributor to adipokine dysregulation. Accordingly, adipocytes of obese
      subjects overproduced adipokines in response to direct exposure of TNF-alpha.
      This hyperresponsiveness was mediated by TNF-alpha receptor 1 and hyperactivation
      of the nuclear factor-kappaB (NF-kappaB) pathway. Correspondingly, NF-kappaB
      activity was increased in adipocytes of obese subjects and correlated with
      adipocyte size, adipokine expression, and in vivo insulin resistance. Eventually
      adipokine overexpression in adipocytes of obese subjects was prevented by NF
      kappaB inhibitors. CONCLUSIONS: In obesity, TNF-alpha that is [corrected] over
      other SVC-secreted factors, a crucial determinant of adipokine dysregulation acts
      on enlarged adipocytes, which are hyperresponsive to this triggering signal
      [corrected]

PMID- 19174497
TI  - Vildagliptin enhances islet responsiveness to both hyper- and hypoglycemia in
      patients with type 2 diabetes.
AB  - CONTEXT: Dipeptidyl peptidase-4 inhibitors act by increasing plasma levels of
      glucagon-like peptide-1 and suppressing excessive glucagon secretion in patients
      with type 2 diabetes. However, their effects on the glucagon response to
      hypoglycemia are not established. OBJECTIVE: The aim of the study was to assess
      effects of the dipeptidyl peptidase-4 inhibitor vildagliptin on alpha-cell
      response to hyper- and hypoglycemia. DESIGN: We conducted a single-center,
      randomized, double-blind, placebo-controlled, two-period crossover study of 28-d
      treatment, with a 4-wk between-period washout. PATIENTS: We studied drug-naive
      patients with type 2 diabetes and baseline glycosylated hemoglobin of 7.5% or
      less. INTERVENTION: Participants received vildagliptin (100 mg/d) or placebo as
      outpatients. PRIMARY OUTCOME MEASURE(S): We measured the following: 1) change in
      plasma glucagon levels during hypoglycemic (2.5 mm glucose) clamp; and 2)
      incremental (Delta) glucagon area under the concentration-time curve from time 0
      to 60 min (AUC(0-60 min)) during standard meal test. Before the study, it was
      hypothesized that vildagliptin would suppress glucagon secretion during meal
      tests and enhance the glucagon response to hypoglycemia. RESULTS: The mean change
      in glucagon during hypoglycemic clamp was 46.7 +/- 6.9 ng/liter with vildagliptin
      treatment and 33.9 +/- 6.7 ng/liter with placebo; the between-treatment
      difference was 12.8 +/- 7.0 ng/liter (P = 0.039), representing a 38% increase
      with vildagliptin. In contrast, the mean glucagon DeltaAUC(0-60 min) during meal
      test with vildagliptin was 512 +/- 163 ng/liter x min vs. 861 +/- 130 ng/liter x
      min with placebo; the between-treatment difference was -349 +/- 158 ng/liter x
      min (P = 0.019), representing a 41% decrease with vildagliptin. CONCLUSIONS:
      Vildagliptin enhances alpha-cell responsiveness to both the suppressive effects
      of hyperglycemia and the stimulatory effects of hypoglycemia. These effects
      likely contribute to the efficacy of vildagliptin to improve glycemic control as
      well as to its low hypoglycemic potential.

PMID- 19174498
TI  - Homocysteine levels and risk of hip fracture in postmenopausal women.
AB  - BACKGROUND: Recent studies suggest that high homocysteine levels are associated
      with an increased risk of fractures. Homocysteine levels are known to be
      influenced by vitamin B and folate supply or status, and poor renal function can
      result in higher levels independent of nutritional adequacy. OBJECTIVE: The aim
      of the study was to determine the associations between fasting homocysteine
      levels and incident hip fractures, and the effects of other factors on hip
      fracture risk. DESIGN: We conducted a case-control study in the Women's Health
      Initiative Observational Study, a study of postmenopausal women (n = 93,676)
      recruited in the United States. We selected 400 incident cases of hip fracture
      and 400 controls matched on age, ethnicity, and blood draw date among women not
      on osteoporosis therapies. Outcome measures included physician-adjudicated,
      incident hip fractures. Baseline lifestyle and nutritional questionnaires were
      performed. RESULTS: The risk of hip fracture increased 1.38-fold [95% confidence
      interval (CI), 1.14, 1.66] for each sd increase in serum homocysteine level after
      adjustment for fracture risk factors. This association was not affected by
      adjustment for dietary folate, B6, or B12 intake, but it diminished after
      adjustment for cystatin-C level (odds ratio, 1.08; 95% CI, 0.66-1.79), a measure
      of renal function not affected by muscle mass. Among women in the highest
      quartile of homocysteine and cystatin-C compared to those without elevations in
      either biomarker, the risk of hip fracture was substantially elevated (odds
      ratio, 2.8; 95% CI, 1.61-4.87). CONCLUSIONS: This study indicates that high
      homocysteine levels are associated with an increased risk of hip fracture, which
      could be accounted for by poor renal function.

PMID- 19174499
TI  - Effect of Roux-en-Y gastric bypass surgery on the sex steroids and quality of
      life in obese men.
AB  - CONTEXT: The effect of bariatric surgery on the reproductive function of obese
      men is not entirely elucidated. OBJECTIVE: The aim of the study was to define the
      effect of Roux-En-Y gastric bypass surgery on the reproductive hormones and
      sexual function in obese men. DESIGN AND SETTING: The cohort was followed for 2
      yr at a clinical research center. PATIENTS: Sixty-four severely obese men (22 who
      had gastric bypass surgery and 42 controls) participated in the study.
      INTERVENTION(S): Anthropometrics [weight, body mass index (BMI), and percentage
      body fat] and reproductive hormones were measured. The sexual quality of life was
      assessed using the Impact of Weight on the Quality Of Life-Lite questionnaire.
      MAIN OUTCOME MEASURE(S): Reproductive hormones and sexual quality of life were
      measured. RESULTS: The mean age was 48.9 +/- 1.2 yr. At baseline, mean weight was
      333.0 +/- 7.1 lb, BMI was 46.2 +/- 0.9 kg/m(2), and total testosterone was 339.9
      +/- 21.32 ng/dl. BMI correlated positively with estradiol and negatively with
      total and free testosterone. Indices of dissatisfaction with sexual quality of
      life correlated positively with measures of obesity. Difficult sexual performance
      and low sexual desire correlated negatively with free and total testosterone (r =
      -0.273, P = 0.038; and r = -0.267, P = 0.042, respectively). After 2 yr, the
      gastric bypass surgery group had a significant decrease in BMI (-16.6 +/- 1.2 vs.
      -0.46 +/- 0.51 kg/m(2)) and estradiol (-8.1 +/- 2.4 vs. 1.6 +/- 1.4 pg/ml) and
      had an increase in total testosterone (310.8 +/- 47.6 vs. 14.2 +/- 15.3 ng/dl)
      and free testosterone (45.2 +/- 5.1 vs. -0.4 +/- 3.0 pg/ml). Sexual quality of
      life was improved after gastric bypass surgery. CONCLUSION: Hormonal alterations
      and diminished sexual quality of life among obese men are related to degree of
      obesity, and both are improved after gastric bypass surgery.

PMID- 19174500
TI  - The effects of recombinant human leptin on visceral fat, dyslipidemia, and
      insulin resistance in patients with human immunodeficiency virus-associated
      lipoatrophy and hypoleptinemia.
AB  - CONTEXT: Leptin deficiency is associated with dyslipidemia and insulin resistance
      in animals and humans with lipoatrophy; leptin replacement ameliorates these
      abnormalities. OBJECTIVE: The objective of the study was to evaluate the effects
      of leptin therapy in lipoatrophic HIV-infected patients with dyslipidemia and
      hypoleptinemia. DESIGN: This was a 6-month, open-label, proof-of-principle pilot
      study. SETTING: Metabolic ward studies were performed before and 3 and 6 months
      after leptin treatment. PARTICIPANTS: Participants included eight HIV-infected
      men with lipoatrophy, fasting triglycerides greater than 300 mg/dl, and serum
      leptin less than 3 ng/ml. INTERVENTION: Recombinant human leptin was given by sc
      injection (0.01 mg/kg and 0.03 mg/kg twice daily for successive 3 month periods).
      OUTCOME MEASURES: Measures included fat distribution by magnetic resonance
      imaging and dual-energy X-ray absorptiometry; fasting lipids; insulin sensitivity
      by euglycemic hyperinsulinemic clamp; endogenous glucose production,
      gluconeogenesis, glycogenolysis, and whole-body lipolysis by stable isotope
      tracer studies; oral glucose tolerance testing; liver fat by proton magnetic
      resonance spectroscopy; and safety. RESULTS: Visceral fat decreased by 32% (P =
      0.001) with no changes in peripheral fat. There were significant decreases in
      fasting total (15%, P = 0.012), direct low-density lipoprotein (20%, P = 0.002),
      and non-high-density lipoprotein (19%, P = 0.005) cholesterol. High-density
      lipoprotein cholesterol increased. Triglycerides, whole-body lipolysis, and free
      fatty acids decreased during fasting and hyperinsulinemia. Fasting insulin
      decreased. Endogenous glucose production decreased during fasting and
      hyperinsulinemia, providing evidence of improved hepatic insulin sensitivity.
      Leptin was well tolerated but decreased lean mass. CONCLUSIONS: Leptin treatment
      was associated with marked improvement in dyslipidemia. Hepatic insulin
      sensitivity improved and lipolysis decreased. Visceral fat decreased with no
      exacerbation of peripheral lipoatrophy. Results from this pilot study suggest
      that leptin warrants further study in patients with HIV-associated lipoatrophy.

PMID- 19174501
TI  - Small vessel remodeling and impaired endothelial-dependent dilatation in
      subcutaneous resistance arteries from patients with acromegaly.
AB  - CONTEXT: Patients with acromegaly have increased morbidity and mortality,
      predominantly from cardiovascular disease. Hypertension and diabetes are more
      prevalent, and both cause small vessel remodeling and endothelial dysfunction.
      OBJECTIVE: To understand the structure and function of small arteries in
      acromegaly, sc blood vessels from gluteal fat biopsies were harvested from 18
      patients with active disease (AD; age, 56 +/- 15 yr; 14 males), 23 patients in
      remission (CD; age, 55 +/- 12 yr; 15 males), and 20 healthy controls (age, 55 +/-
      11 yr; 10 males) and examined in vitro using pressure myography. DESIGN:
      Contractile responses to cumulative noradrenaline concentrations were recorded
      and followed by dose-dependent dilator responses to acetylcholine. The
      acetylcholine protocol was repeated after incubation with a nitric oxide synthase
      inhibitor (N-nitro-L-arginine methyl ester) and cyclooxygenase inhibitor
      (indomethacin). After perfusion with Ca(2+)-free physiological saline solution,
      structural measurements were recorded at varying intraluminal pressures (3-180 mm
      Hg). RESULTS: Wall thickness and wall:lumen ratio were increased in AD, reduced
      with treatment but remained greater in CD than controls. Wall cross-sectional
      area was increased in AD vs. controls (P < 0.001), decreased with treatment (AD
      vs. CD, P < 0.001), but remained higher than controls (CD vs. controls, P =
      0.015). Growth index was increased in AD (20%) compared to controls (CD, 9%).
      Contractility was similar in all groups. Endothelial-dependent dysfunction was
      evident in AD compared with CD (P < 0.001) and controls (P < 0.01). Dilation did
      not change after N-nitro-L-arginine methyl ester but was impaired after
      indomethacin incubation. CONCLUSION: Active acromegaly is associated with
      hypertrophic remodeling of the vascular wall and embarrassed endothelial function
      due to reduced nitric oxide and endothelium-derived hyperpolarizing factor
      bioavailability, both of which may contribute to the early mortality from
      cardiovascular disease.

PMID- 19174502
TI  - Implementing a 48 h EWTD-compliant rota for junior doctors in the UK does not
      compromise patients' safety: assessor-blind pilot comparison.
AB  - BACKGROUND: There are currently no field data about the effect of implementing
      European Working Time Directive (EWTD)-compliant rotas in a medical setting.
      Surveys of doctors' subjective opinions on shift work have not provided reliable
      objective data with which to evaluate its efficacy. AIM: We therefore studied the
      effects on patient's safety and doctors' work-sleep patterns of implementing an
      EWTD-compliant 48 h work week in a single-blind intervention study carried out
      over a 12-week period at the University Hospitals Coventry & Warwickshire NHS
      Trust. We hypothesized that medical error rates would be reduced following the
      new rota. METHODS: Nineteen junior doctors, nine studied while working an
      intervention schedule of <48 h per week and 10 studied while working traditional
      weeks of <56 h scheduled hours in medical wards. Work hours and sleep duration
      were recorded daily. Rate of medical errors (per 1000 patient-days), identified
      using an established active surveillance methodology, were compared for the
      Intervention and Traditional wards. Two senior physicians blinded to rota
      independently rated all suspected errors. RESULTS: Average scheduled work hours
      were significantly lower on the intervention schedule [43.2 (SD 7.7) (range 26.0
      60.0) vs. 52.4 (11.2) (30.0-77.0) h/week; P < 0.001], and there was a non
      significant trend for increased total sleep time per day [7.26 (0.36) vs. 6.75
      (0.40) h; P = 0.095]. During a total of 4782 patient-days involving 481
      admissions, 32.7% fewer total medical errors occurred during the intervention
      than during the traditional rota (27.6 vs. 41.0 per 1000 patient-days, P =
      0.006), including 82.6% fewer intercepted potential adverse events (1.2 vs. 6.9
      per 1000 patient-days, P = 0.002) and 31.4% fewer non-intercepted potential
      adverse events (16.6 vs. 24.2 per 1000 patient-days, P = 0.067). Doctors reported
      worse educational opportunities on the intervention rota. CONCLUSIONS: Whilst
      concerns remain regarding reduced educational opportunities, our study supports
      the hypothesis that a 48 h work week coupled with targeted efforts to improve
      sleep hygiene improves patient safety.

PMID- 19174503
TI  - Effect of hepatitis A vaccination programs for migrant children on the incidence
      of hepatitis A in The Netherlands.
AB  - BACKGROUND: Since 1998 Municipal Public Health Services (MPHSs) in The
      Netherlands carried out Hepatitis A (HAV) vaccination programs for Turkish and
      Moroccan children to reduce import and secondary HAV infections. The aim of this
      study was to assess the effects of the programs on HAV incidence. METHODS: MPHSs
      were questioned about HAV vaccination programs for migrant children. Notification
      data of HAV over the period 1995-2006 were analysed. RESULTS: Since 1998, 19
      MPHSs (58%) organized vaccination programs for Turkish and Moroccan children. A
      large variation in the range of activities in HAV vaccination programs was
      observed. In The Netherlands, HAV incidence declined, from 6.5 per 100,000
      inhabitants in 1995 to 1.3 in 2005. HAV incidence in children of Turkish and
      Moroccan decent declined from 70.3 per 100,000 in 2000 to 13.5 per 100,000 in
      2005. Regions where MPHSs organized vaccination campaigns had the steepest
      decline in HAV incidence. CONCLUSION: The decline in HAV incidence in The
      Netherlands coincided with that observed for the rest of Europe. Therefore, also
      other causes than the enhanced vaccination programs could have contributed to
      this effect. At present, low priority is placed on continuing these HAV
      vaccination programs, as in areas without enhanced programs the incidence also
      declined to very low levels. Because HAV is still endemic in Morocco and Turkey,
      it remains important that all travellers to these countries are vaccinated
      against HAV, regardless of their country of origin.

PMID- 19174504
TI  - Assessing changes in mortality inequalities in Israel using a period-specific
      measure of socio-economic position, 1983-92 and 1995-2004.
AB  - Changes in mortality inequalities among middle-aged individuals were examined
      using a household amenities variable with analogous interpretation and
      distribution over time. Data were taken from the census-based Israel Longitudinal
      Mortality Studies I (1983-92, n = 91 656) and II (1995-2004, n = 120 973).
      Mortality differentials in socio-economic gradients for high household amenities
      showed relative increases over time in overall and cardiovascular disease
      mortality for resident men (44% and 42%, respectively) and women (45% and 82%,
      respectively). Temporal influences on measures of socio-economic position did not
      affect our findings of a widening in socio-economic inequalities in mortality.

PMID- 19174505
TI  - Identification and exploration of herb-drug combinations used by cancer patients.
AB  - INTRODUCTION: This survey aims to identify herb-chemotherapeutic drug
      combinations in a defined group of cancer patients and to explore possible
      clinical consequences of these combinations. METHODS: Herb-chemotherapeutic drug
      combinations were identified among adult cancer patients, and clinical
      consequences of the combinations were explored by literature searches in medical
      databases on possible mutual effects on similar cytochrome P-450 metabolising
      enzymes (CYPs) and/or the P-glycoprotein (P-gp) transporter. RESULTS: Among 42
      cancer patients using herbal remedies concurrently with chemotherapy, 136 two
      agent herb-drug combinations were registered and 47 different potential herb-drug
      interactions were identified on the level of CYP metabolism and P-gp transport in
      vitro. Garlic, ginger, green tea and noni juice were the herbal remedies most
      frequently used in such combinations. For 48 % of the herbal remedies identified
      no literature data exist on their interaction potentials. Clinical studies were
      available for four herbal remedies only. Minor clinical potential for CYP
      interactions in humans was indicated for green tea and Echinacea. P-gp
      interactions were only investigated for garlic, which showed a significant
      interaction potential both in vivo and in vitro. CONCLUSION: The large number of
      in vitro potential herb-drug interactions identified urge for more clinical
      pharmacokinetic interaction studies in humans.

PMID- 19174506
TI  - Trastuzumab and doxorubicin-related cardiotoxicity and the cardioprotective role
      of exercise.
AB  - Women diagnosed with breast cancer typically undergo a multimodal approach to
      treating their disease. The treatments used often result in sequelae such as
      fatigue, hair loss, nausea and vomiting, and functional impairment. Many of these
      sequelae can be controlled or eliminated with pharmacological, physical, or
      social interventions. However, 2 effective cytotoxic agents, doxorubicin and
      trastuzumab, are associated with a potentially life-threatening sequela,
      cardiotoxicity. Currently, these agents are dosage and duration limited to
      circumvent cardiac damage. Exercise prior to and during the administration of
      these agents is emerging as a possible cardioprotective intervention based on the
      findings of animal model studies. Incorporating exercise into the breast cancer
      treatment trajectory may eliminate the dosage and duration restrictions of these
      antineoplastic agents and ultimately affect survival and quality of life. The
      authors present the pharmacological mechanism for each agent and the exciting
      results of animal model studies that lay the groundwork for future clinical
      trials.

PMID- 19174507
TI  - Inhibitive effect of artemether on tumor growth and angiogenesis in the rat C6
      orthotopic brain gliomas model.
AB  - To explore the inhibitive effect of artemether on glioma growth and angiogenesis
      in brain tumor bearing SD rat. MTT assay was used to evaluate the inhibitory
      effect of artemether treatment on C6 glioma cells. Forty SD rats which were
      subcutaneous planted with SD rat C6 glioma cell to establish SD rat orthotopic
      glioma model were divided resourcefully into 5 groups. each group was 8 rats.
      Length-path (a mm) and short-path (b mm) of tumor each rat was measured. Tumor
      volume was calculated using the following formula: V (mm(3)) = a(2)bpi/6.
      Microvessel density (MVD) in different therapy groups was significantly lower
      than that in normal saline control group and brain glioma volume in different
      therapy groups was significantly smaller than that in normal saline control
      group. There were remarkably inhibitory effects of artmeter on brain glioma
      growth and angiogenesis in SD rats and the mechanism that artemether inhibited
      brain glioma growth might be penetrating the blood-brain barrier and inhibiting
      angiogenesis.

PMID- 19174508
TI  - The Psi(m) depolarization that accompanies mitochondrial Ca2+ uptake is greater
      in mutant SOD1 than in wild-type mouse motor terminals.
AB  - The electrical gradient across the mitochondrial inner membrane (Psi(m)) is
      established by electron transport chain (ETC) activity and permits mitochondrial
      Ca(2+) sequestration. Using rhodamine-123, we determined how repetitive nerve
      stimulation (100 Hz) affects Psi(m) in motor terminals innervating mouse levator
      auris muscles. Stimulation-induced Psi(m) depolarizations in wild-type (WT)
      terminals were small (<5 mV at 30 degrees C) and reversible. These
      depolarizations depended on Ca(2+) influx into motor terminals, as they were
      inhibited when P/Q-type Ca(2+) channels were blocked with omega-agatoxin.
      Stimulation-induced Psi(m) depolarization and elevation of cytosolic [Ca(2+)]
      both increased when complex I of the ETC was partially inhibited by low
      concentrations of rotenone (25-50 nmol/l). This finding is consistent with the
      hypothesis that acceleration of ETC proton extrusion normally limits the
      magnitude of Psi(m) depolarization during mitochondrial Ca(2+) uptake, thereby
      permitting continued Ca(2+) uptake. Compared with WT, stimulation-induced
      increases in rhodamine-123 fluorescence were approximately 5 times larger in
      motor terminals from presymptomatic mice expressing mutations of human superoxide
      dismutase I (SOD1) that cause familial amyotrophic lateral sclerosis (SOD1-G85R,
      which lacks dismutase activity; SOD1-G93A, which retains dismutase activity).
      Psi(m) depolarizations were not significantly altered by expression of WT human
      SOD1 or knockout of SOD1 or by inhibiting opening of the mitochondrial
      permeability transition pore with cyclosporin A. We suggest that an early
      functional consequence of the association of SOD1-G85R or SOD1-G93A with
      motoneuronal mitochondria is reduced capacity of the ETC to limit Ca(2+)-induced
      Psi(m) depolarization, and that this impairment contributes to disease
      progression in mutant SOD1 motor terminals.

PMID- 19174509
TI  - Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage
      and an uncommitted minor population retaining plasticity.
AB  - Natural regulatory T cells (T(reg)) represent a distinct lineage of T lymphocytes
      committed to suppressive functions, and expression of the transcription factor
      Foxp3 is thought to identify this lineage specifically. Here we report that,
      whereas the majority of natural CD4(+)Foxp3(+) T cells maintain stable Foxp3
      expression after adoptive transfer to lymphopenic or lymphoreplete recipients, a
      minor fraction enriched within the CD25(-) subset actually lose it. Some of those
      Foxp3(-) T cells adopt effector helper T cell (T(h)) functions, whereas some
      retain "memory" of previous Foxp3 expression, reacquiring Foxp3 upon activation.
      This minority "unstable" population exhibits flexible responses to cytokine
      signals, relying on transforming growth factor-beta to maintain Foxp3 expression
      and responding to other cytokines by differentiating into effector T(h) in vitro.
      In contrast, CD4(+)Foxp3(+)CD25(high) T cells are resistant to such conversion to
      effector T(h) even after many rounds of cell division. These results demonstrate
      that natural Foxp3(+) T cells are a heterogeneous population consisting of a
      committed T(reg) lineage and an uncommitted subpopulation with developmental
      plasticity.

PMID- 19174510
TI  - TAF4 takes flight.

PMID- 19174511
TI  - A prion of yeast metacaspase homolog (Mca1p) detected by a genetic screen.
AB  - Saccharomyces cerevisiae can be infected with four amyloid-based prions: [URE3],
      [PSI(+)], [PIN(+)], and [SWI(+)], due to self-propagating aggregation of Ure2p,
      Sup35p, Rnq1p and Swi1p, respectively. We searched for new prions of yeast by
      fusing random segments of yeast DNA to SUP35MC, encoding the Sup35 protein
      lacking its own prion domain, selecting clones in which Sup35MC function was
      impaired. Three different clones contained parts of the Q/N-rich amino-terminal
      domain of Mca1p/Yca1p with the Sup35 part of the fusion protein partially
      inactive. This inactivity was dominant, segregated 4:0 in meiosis, and was
      efficiently transferred by cytoplasmic mixing. The inactivity was cured by
      overexpression of Hsp104, but the prion could arise again in the cured strain
      (reversible curing). Overproduction of the Mca1 N-terminal domain induced the de
      novo appearance of the prion form of the fusion. The prion state, which we name
      [MCA], was transmitted to the chromosomally encoded Mca1p based on genetic,
      cytological and biochemical tests.

PMID- 19174512
TI  - Functional expression of the olfactory signaling system in the kidney.
AB  - Olfactory-like chemosensory signaling occurs outside of the olfactory epithelium.
      We find that major components of olfaction, including olfactory receptors (ORs),
      olfactory-related adenylate cyclase (AC3) and the olfactory G protein (G(olf)),
      are expressed in the kidney. AC3 and G(olf) colocalize in renal tubules and in
      macula densa (MD) cells which modulate glomerular filtration rate (GFR). GFR is
      significantly reduced in AC3(-/-) mice, suggesting that AC3 participates in GFR
      regulation. Although tubuloglomerular feedback is normal in these animals, they
      exhibit significantly reduced plasma renin levels despite up-regulation of COX-2
      expression and nNOS activity in the MD. Furthermore, at least one member of the
      renal repertoire of ORs is expressed in a MD cell line. Thus, key components of
      olfaction are expressed in the renal distal nephron and may play a sensory role
      in the MD to modulate both renin secretion and GFR.

PMID- 19174513
TI  - Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry.
AB  - Although the transcriptome, proteome, and interactome of several eukaryotic model
      organisms have been described in detail, lipidomes remain relatively
      uncharacterized. Using Saccharomyces cerevisiae as an example, we demonstrate
      that automated shotgun lipidomics analysis enabled lipidome-wide absolute
      quantification of individual molecular lipid species by streamlined processing of
      a single sample of only 2 million yeast cells. By comparative lipidomics, we
      achieved the absolute quantification of 250 molecular lipid species covering 21
      major lipid classes. This analysis provided approximately 95% coverage of the
      yeast lipidome achieved with 125-fold improvement in sensitivity compared with
      previous approaches. Comparative lipidomics demonstrated that growth temperature
      and defects in lipid biosynthesis induce ripple effects throughout the molecular
      composition of the yeast lipidome. This work serves as a resource for molecular
      characterization of eukaryotic lipidomes, and establishes shotgun lipidomics as a
      powerful platform for complementing biochemical studies and other systems-level
      approaches.

PMID- 19174514
TI  - Multiple conformational switches in a GTPase complex control co-translational
      protein targeting.
AB  - The "GTPase switch" paradigm, in which a GTPase switches between an active, GTP
      bound state and an inactive, GDP-bound state through the recruitment of
      nucleotide exchange factors (GEFs) or GTPase activating proteins (GAPs), has been
      used to interpret the regulatory mechanism of many GTPases. A notable exception
      to this paradigm is provided by two GTPases in the signal recognition particle
      (SRP) and the SRP receptor (SR) that control the co-translational targeting of
      proteins to cellular membranes. Instead of the classical "GTPase switch," both
      the SRP and SR undergo a series of discrete conformational rearrangements during
      their interaction with one another, culminating in their reciprocal GTPase
      activation. Here, we show that this series of rearrangements during SRP-SR
      binding and activation provide important control points to drive and regulate
      protein targeting. Using real-time fluorescence, we showed that the cargo for SRP
      -ribosomes translating nascent polypeptides with signal sequences--accelerates
      SRP.SR complex assembly over 100-fold, thereby driving rapid delivery of cargo to
      the membrane. A series of subsequent rearrangements in the SRP x SR GTPase
      complex provide important driving forces to unload the cargo during late stages
      of protein targeting. Further, the cargo delays GTPase activation in the SRP.SR
      complex by 8-12 fold, creating an important time window that could further
      improve the efficiency and fidelity of protein targeting. Thus, the SRP and SR
      GTPases, without recruiting external regulatory factors, constitute a self
      sufficient system that provides exquisite spatial and temporal control of a
      complex cellular process.

PMID- 19174515
TI  - Active-site architecture and catalytic mechanism of the lipid A deacylase LpxR of
      Salmonella typhimurium.
AB  - The lipid A portion of lipopolysaccharide, the major component of the outer
      leaflet of the outer membrane of gram-negative bacteria, is toxic to humans.
      Modification of lipid A by enzymes often reduces its toxicity. The outer-membrane
      protein LpxR from Salmonella typhimurium is a lipid A-modifying enzyme. It
      removes the 3'-acyloxyacyl moiety of the lipid A portion of lipopolysaccharide in
      a Ca(2+)-dependent manner. Here, we present the crystal structure of S.
      typhimurium LpxR, crystallized in the presence of zinc ions. The structure, a 12
      stranded beta-barrel, reveals that the active site is located between the barrel
      wall and an alpha-helix formed by an extracellular loop. Based on site-directed
      mutagenesis and modeling of a substrate on the active site, we propose a
      catalytic mechanism similar to that of phospholipase A2, in which a Ca(2+) forms
      the oxyanion hole and a histidine activates a water molecule (or a cascade of two
      water molecules) that subsequently attacks the carbonyl oxygen of the scissile
      bond.

PMID- 19174516
TI  - VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier
      breakdown.
AB  - Breakdown of the blood-brain barrier (BBB) is an early and significant event in
      CNS inflammation. Astrocyte-derived VEGF-A has been implicated in this response,
      but the underlying mechanisms remain unresolved. Here, we identify the
      endothelial transmembrane tight junction proteins claudin-5 (CLN-5) and occludin
      (OCLN) as targets of VEGF-A action. Down-regulation of CLN-5 and OCLN accompanied
      up-regulation of VEGF-A and correlated with BBB breakdown in experimental
      autoimmune encephalomyelitis, an animal model of CNS inflammatory disease. In
      cultures of brain microvascular endothelial cells, VEGF-A specifically down
      regulated CLN-5 and OCLN protein and mRNA. In mouse cerebral cortex,
      microinjection of VEGF-A disrupted CLN-5 and OCLN and induced loss of barrier
      function. Importantly, functional studies revealed that expression of recombinant
      CLN-5 protected brain microvascular endothelial cell cultures from a VEGF-induced
      increase in paracellular permeability, whereas recombinant OCLN expressed under
      the same promoter was not protective. Previous studies have shown CLN-5 to be a
      key determinant of trans-endothelial resistance at the BBB. Our findings suggest
      that its down-regulation by VEGF-A constitutes a significant mechanism in BBB
      breakdown.

PMID- 19174517
TI  - Independent saturation of three TrpRS subsites generates a partially assembled
      state similar to those observed in molecular simulations.
AB  - Two new crystal structures of Bacillus stearothermophilus tryptophanyl-tRNA
      synthetase (TrpRS) afford evidence that a closed interdomain hinge angle requires
      a covalent bond between AMP and an occupant of either pyrophosphate or tryptophan
      subsite. They also are within experimental error of a cluster of structures
      observed in a nonequilibrium molecular dynamics simulation showing partial active
      site assembly. Further, the highest energy structure in a minimum action pathway
      computed by using elastic network models for Open and Pretransition state (PreTS)
      conformations for the fully liganded TrpRS monomer is intermediate between that
      simulated structure and a partially disassembled structure from a nonequilibrium
      molecular dynamics trajectory for the unliganded PreTS. These mutual
      consistencies provide unexpected validation of inferences drawn from molecular
      simulations.

PMID- 19174518
TI  - Waltzing alpha-helices.

PMID- 19174519
TI  - Microarray analysis sheds light on the dedifferentiating role of agouti signal
      protein in murine melanocytes via the Mc1r.
AB  - The melanocortin-1 receptor (MC1R) is a key regulator of pigmentation in mammals
      and is tightly linked to an increased risk of skin cancers, including melanoma,
      in humans. Physiologically activated by alpha-melanocyte stimulating hormone
      (alphaMSH), MC1R function can be antagonized by a secreted factor, agouti signal
      protein (ASP), which is responsible for the lighter phenotypes in mammals
      (including humans), and is also associated with increased risk of skin cancer. It
      is therefore of great interest to characterize the molecular effects elicited by
      those MC1R ligands. In this study, we determined the gene expression profiles of
      murine melan-a melanocytes treated with ASP or alphaMSH over a 4-day time course
      using genome-wide oligonucleotide microarrays. As expected, there were
      significant reductions in expression of numerous melanogenic proteins elicited by
      ASP, which correlates with its inhibition of pigmentation. ASP also unexpectedly
      modulated the expression of genes involved in various other cellular pathways,
      including glutathione synthesis and redox metabolism. Many genes up-regulated by
      ASP are involved in morphogenesis (especially in nervous system development),
      cell adhesion, and extracellular matrix-receptor interactions. Concomitantly, ASP
      enhanced the migratory potential and the invasiveness of melanocytic cells in
      vitro. These results demonstrate the role of ASP in the dedifferentiation of
      melanocytes, identify pigment-related genes targeted by ASP and by alphaMSH, and
      provide insights into the pleiotropic molecular effects of MC1R signaling that
      may function during development and may affect skin cancer risk.

PMID- 19174520
TI  - Chromosomal location targets different MYC family gene members for oncogenic
      translocations.
AB  - The MYC family of cellular oncogenes includes c-Myc, N-myc, and L-myc, which
      encode transcriptional regulators involved in the control of cell proliferation
      and death. Accordingly, these genes become aberrantly activated and expressed in
      specific types of cancers. For example, c-Myc translocations occur frequently in
      human B lymphoid tumors, while N-myc gene amplification is frequent in human
      neuroblastomas. The observed association between aberrations in particular MYC
      family genes and specific subsets of malignancies might reflect, at least in
      part, tissue-specific differences in expression or function of a given MYC gene.
      Since c-Myc and N-myc share substantial functional redundancy, another factor
      that could influence tumor-specific gene activation would be mechanisms that
      target aberrations (e.g., translocations) in a given MYC gene in a particular
      tumor progenitor cell type. We have previously shown that mice deficient for the
      DNA Ligase4 (Lig4) nonhomologous DNA end-joining factor and the p53 tumor
      suppressor routinely develop progenitor (pro)-B cell lymphomas that harbor
      translocations leading to c-Myc amplification. Here, we report that a modified
      allele in which the c-Myc coding sequence is replaced by N-myc coding sequence
      (NCR allele) competes well with the wild-type c-Myc allele as a target for
      oncogenic translocations and amplifications in the Lig4/p53-deficient pro-B cell
      lymphoma model. Tumor onset, type, and cytological aberrations are similar in
      tumors harboring either the wild-type c-Myc gene or the NCR allele. Our results
      support the notion that particular features of the c-Myc locus select it as a
      preferential translocation/amplification target, compared to the endogenous N-myc
      locus, in Lig4/p53-deficient pro-B cell lymphomas.

PMID- 19174521
TI  - Biosynthesis of the Caenorhabditis elegans dauer pheromone.
AB  - To sense its population density and to trigger entry into the stress-resistant
      dauer larval stage, Caenorhabditis elegans uses the dauer pheromone, which
      consists of ascaroside derivatives with short, fatty acid-like side chains.
      Although the dauer pheromone has been studied for 25 years, its biosynthesis is
      completely uncharacterized. The daf-22 mutant is the only known mutant defective
      in dauer pheromone production. Here, we show that daf-22 encodes a homolog of
      human sterol carrier protein SCPx, which catalyzes the final step in peroxisomal
      fatty acid beta-oxidation. We also show that dhs-28, which encodes a homolog of
      the human d-bifunctional protein that acts just upstream of SCPx, is also
      required for pheromone production. Long-term daf-22 and dhs-28 cultures develop
      dauer-inducing activity by accumulating less active, long-chain fatty acid
      ascaroside derivatives. Thus, daf-22 and dhs-28 are required for the biosynthesis
      of the short-chain fatty acid-derived side chains of the dauer pheromone and link
      dauer pheromone production to metabolic state.

PMID- 19174522
TI  - The Indian Ocean Dipole and malaria risk in the highlands of western Kenya.
AB  - Epidemics of malaria in the East African highlands in the last 2 decades have
      often been associated with climate variability, particularly the El Nino-Southern
      Oscillation (ENSO). However, there are other factors associated with malaria risk
      and there is increased interest in the influences of the Indian Ocean Dipole
      (IOD), a climate mode of coupled ocean-atmosphere variability, on East African
      rainfall. This study explores the relationship between IOD and the number of
      malaria patients in 7 hospitals from 2 districts in the western Kenyan highlands,
      controlling for the effects of ENSO. We examined temporal patterns (1982-2001) in
      the number of malaria cases in relation to the dipole mode index (DMI), defined
      as the difference in sea surface temperature anomaly between the western (10
      degrees S-10 degrees N, 50 degrees-70 degrees E) and eastern (10 degrees S-0
      degrees, 90 degrees-110 degrees E) tropical Indian Ocean. We used Poisson
      regression models, adjusted for ENSO index Nino 3 region (NINO3), seasonal and
      interannual variations. The number of malaria patients per month increased by
      3.4%-17.9% for each 0.1 increase above a DMI threshold (3-4 months lag). Malaria
      cases increased by 1.4%-10.7% per month, for each 10 mm increase in monthly
      rainfall (2-3 months lag). In 6 of 7 places, there was no evidence of an
      association between NINO3 and the number of malaria cases after adjusting for the
      effect of DMI. This study suggests that the number of malaria cases in the
      western Kenyan highlands increases with high DMI in the months preceding hospital
      visits.

PMID- 19174523
TI  - Igf1r as a therapeutic target in a mouse model of basal-like breast cancer.
AB  - Considering the strong association between dysregulated insulin-like growth
      factor (IGF) signaling and various human cancers, we have used an expedient
      combination of genetic analysis and pharmacological treatment to evaluate the
      potential of the type 1 IGF receptor (Igf1r) for targeted anticancer therapy in a
      mouse model of mammary tumorigenesis. In this particular strain of genetically
      modified animals, histopathologically heterogeneous invasive carcinomas
      exhibiting up-regulation of the Igf1r gene developed extremely rapidly by mammary
      gland-specific overexpression of constitutively active oncogenic Kras* (mutant
      Kras(G12D)). Immunophenotyping data and expression profiling analyses showed
      that, except for a minor luminal component, these mouse tumors resembled basal
      like human breast cancers. This is a group of aggressive tumors of poor prognosis
      for which there is no targeted therapy currently available, and it includes a
      subtype correlating with KRAS locus amplification. Conditional ablation of Igf1r
      in the mouse mammary epithelium increased the latency of Kras*-induced tumors
      very significantly (approximately 11-fold in comparison with the intact model),
      whereas treatment of tumor-bearing animals by administration of picropodophyllin
      (PPP), a specific Igf1r inhibitor, resulted in a dramatic decrease in tumor mass
      of the main forms of basal-like carcinomas. PPP also was effective against
      xenografts of the human basal-like cancer cell line MDA-MB-231, which carries a
      KRAS(G13D) mutation.

PMID- 19174524
TI  - Phosphorylation keeps PTEN phosphatase closed for business.

PMID- 19174525
TI  - CD5 sweetens lymphocyte responses.

PMID- 19174526
TI  - EVAR for the treatment of ruptured AAA.
AB  - Endovascular repair (EVAR) for ruptured abdominal aortic aneurysm (AAA) has been
      held out as a safer, less invasive alternative to open surgery with the potential
      to significantly reduce in-hospital mortality. Despite the inherent biases that
      accompany comparison of the 2 treatment modalities, there appears to be a clear
      role for EVAR for select patients in select centers. To successfully treat
      patients with ruptured AAA both open and endovascular modalities should be
      available and clear protocols using a team approach must be developed.

PMID- 19174527
TI  - Cerebral air embolism recognized by cerebral oximetry.
AB  - Absolute cerebral oximetry is useful in clinical settings to identify
      "catastrophic events" that may occur during the course of surgeries that would
      otherwise have gone unrecognized. This study reports a case in which cerebral
      desaturation occurred after commencing cardiopulmonary bypass. Consequently, the
      source of air entrainment was discovered and therapeutic measures implemented.

PMID- 19174528
TI  - Endovascular treatment of carotid stump syndrome.
AB  - We present the case of a carotid stump syndrome in a 72-year-old woman with a 3
      day history of recurrent transient ischemic attacks. Computed tomographic
      angiography showed the occlusion of the ipsilateral internal carotid artery, and
      the presence of an internal stump with ophthalmic reverse flow, confirming the
      suspect of a stump syndrome. The patient underwent stent-graft exclusion of the
      carotid stump; she was last seen 12 months after the procedure when she remained
      totally asymptomatic.

PMID- 19174529
TI  - A randomized trial of home telemonitoring in a typical elderly heart failure
      population in North West London: results of the Home-HF study.
AB  - AIMS: Heart failure chiefly affects the elderly, with frequent emergency
      admissions. Telemonitoring can identify worsening heart failure but previous
      randomized trials have enrolled selected patient populations. The Home-HF study
      examined the impact of home telemonitoring on typical heart failure patients
      discharged from three acute hospitals in North West London, UK. METHODS AND
      RESULTS: Patients hospitalized with heart failure were randomized to
      telemonitoring or usual specialist care. Primary outcome measures were days alive
      and out of hospital. Secondary outcome measures were number and duration of heart
      failure hospitalizations, clinic visits, and quality of life. We recruited 182
      patients. There was no difference in the primary outcome measure in the two
      groups, but there were significantly fewer unplanned hospitalizations for heart
      failure decompensation, and a reduction in clinic and emergency room visits in
      the telemonitoring group. There was no statistically significant difference in
      the mean direct health service costs. CONCLUSION: Home telemonitoring in a
      typical elderly population of heart failure patients produces a similar outcome
      to 'usual' specialist care, but reduces clinic and emergency room visits and
      unplanned heart failure rehospitalizations at little additional cost. This method
      of disease monitoring may allow specialist services to increase the number of
      patients under their care.

PMID- 19174530
TI  - Functional glucocorticoid receptor gene variants do not underlie the high
      variability of 17-hydroxyprogesterone screening values in healthy newborns.
AB  - OBJECTIVE: 17-Hydroxyprogesterone (17-OHP) screening for classical congenital
      adrenal hyperplasia (CAH) is part of many newborn screening programs worldwide.
      Cut-off values are relatively high, and screening sensitivity does not reach
      100%. Recently, the glucocorticoid receptor (GR) N363S-variant has been linked to
      relatively low degree of virilization and comparatively lower 17-OHP serum
      concentrations in clinically diagnosed female CAH patients. We sought to
      determine whether functional GR gene variants, either increasing (N363S, BclI) or
      decreasing GR sensitivity (R23K), underlie the variable 17-OHP screening levels
      in healthy newborns. DESIGN: GR genotypes were compared with 17-OHP screening
      values in 1000 random samples from routine screening. 17-OHP was measured by
      conventional immunoassay (TRFIA) and a liquid chromatography-tandem mass
      spectrometry method (LC-MS/MS), which has been shown to increase screening
      specificity by steroid profiling and avoiding cross-reactions of the 17-OHP
      antibody. RESULTS: There was no significant association of 17-OHP with GR
      genotypes, even after inclusion of gestational and postnatal age as covariates.
      However, among LC-MS/MS steroid measurements, we observed some unexpected trends,
      including lower 11-deoxycortisol concentrations in both 363S- and 23K-carriers.
      For carriers of the frequent BclI variant, linear regression analysis revealed a
      significant increase of 4-androstenedione levels with every mutant allele
      inherited. CONCLUSIONS: Functional GR variants do not underlie the variation of
      17-OHP values observed in healthy individuals. However, whether and to which
      extent genetically determined differences in individual GR sensitivity influence
      17-OHP screening levels in conditions of a pathological hypothalamus-pituitary
      adrenal gland-axis stimulation and thus may explain false-negative screening
      results in those affected by CAH remains to be investigated.

PMID- 19174531
TI  - Presence of pituitary adenylate cyclase activating polypeptide-38 in human plasma
      and milk.
AB  - OBJECTIVE: Pituitary adenylate cyclase activating polypeptide (PACAP) is a
      pleiotropic and multifunctional neuropeptide widely distributed throughout the
      body. It is involved in the regulation of various physiological and
      pathophysiological processes, such as reproduction, thermoregulation, motor
      activity, brain development, neuronal survival, inflammation and pain. Since
      little is known about its distribution in humans, our aim was to examine PACAP-38
      in human plasma. Furthermore, based on the presence of vasoactive intestinal
      peptide, structurally the closest to PACAP, in milk and PACAP and its receptors
      in the mammary gland, our aim was to study PACAP-38 in human milk. DESIGN AND
      METHODS: The presence of PACAP-38 was determined by mass spectrometry in plasma
      samples from healthy male and female volunteers (age: 20-40), as well as in
      plasma and milk samples from lactating women (age: 20-35). PACAP concentration
      was measured with a specific and sensitive RIA. RESULTS: Our results revealed
      that PACAP-38 is present in human plasma, its concentration is relatively stable
      in healthy volunteers and it is not significantly altered by gender, age, food
      intake or hormonal cycle in females. However, PACAP-38 plasma levels
      significantly increased in lactating women having 1-6 month-old babies. Moreover,
      this study is the first which provides evidence for the presence of PACAP-38 in
      the human milk with levels 5-20-fold greater in the milk whey than in the
      respective plasma samples. CONCLUSIONS: We found PACAP-38 in human plasma and its
      increase during the first 6 months of the lactation period. A prominent, nearly
      10-fold higher concentration of this peptide was detected in human milk. Based on
      the literature, several important actions of milk-derived PACAP-38 can be
      suggested such as mammary gland proliferation, nutrient transfer as well as
      regulation of growth/differentiation of certain tissues of the neonates. The
      novelty of the present descriptive data provides a basis for further
      investigations on the mechanism of PACAP-38 secretion in human milk and its
      functional significance.

PMID- 19174532
TI  - Measures of bioavailable serum testosterone and estradiol and their relationships
      with muscle mass, muscle strength and bone mineral density in postmenopausal
      women: a cross-sectional study.
AB  - OBJECTIVE: The physiologic role of circulating endogenous testosterone and
      estrogen concentrations in relation to lean body mass (LBM) and muscle strength
      is not as well documented in postmenopausal women as in elderly men. DESIGN:
      Three hundred and twenty-nine healthy postmenopausal women were randomly selected
      from a general practice population-based sample aged between 55 and 85 years.
      METHODS: Total testosterone and estrogen (TT and TE) and sex hormone-binding
      globulin (SHBG) were determined and estimates of bioavailable testosterone (free
      androgen index (TT/SHBG, FAI), calculated free testosterone (cFT), and estrogen
      (TE/SHBG, ESR) were calculated. Examinations included bone mineral density (BMD)
      of the spine and femoral neck (FN), LBM, maximum quadriceps extension strength
      (MES) and maximum handgrip strength (MGS), timed up-and-go test (TUGT),
      osteocalcin (OC), and urinary deoxy-pyridinoline/creatinine (DPyr). Correlations
      were assessed using Pearson's correlation coefficient (r). RESULTS: With
      advancing age, LBM, MES, MGS, BMD, and ESR significantly declined (range r: 
      0.356 to -0.141) and TUGT, and DPyr significantly increased (range r: 0.135 to
      0.282 (P<0.05)). After age-adjustment, LBM, MES, and BMD in spine and FN were
      significantly related to bioavailable testosterone (range r: 0.146 to 0.193, for
      cFT, and 0.157 to 0.224, for FAI) and to ESR (range r: 0.162 to 0.273). OC and
      DPyr were significantly inversely related to ESR (r: -0.154 and -0.144
      respectively). CONCLUSIONS: Age-related loss of LBM, MES and BMD in
      postmenopausal women is partly dependent on the presence of endogenous
      bioavailable testosterone and estrogen.

PMID- 19174533
TI  - Atherosclerotic risk factors and complications in patients with non-functioning
      adrenal adenomas treated with or without adrenalectomy: a long-term follow-up
      study.
AB  - OBJECTIVE: Despite the increased prevalences of hypertension, type 2 diabetes
      mellitus (T2DM), hyperlipidemy, and obesity in patients with non-functioning
      adrenal adenomas (NFAAs), there is a paucity of data on long-term atherosclerotic
      morbidity as well as the long-term cardiovascular effects of adrenalectomy in
      these patients. DESIGN, PATIENTS, AND METHODS: This retrospective study includes
      the results of baseline and follow-up investigations of 125 patients (29 males
      and 96 females; mean age 60.1 years) with NFAAs referred for endocrine evaluation
      between 1990 and 2001. Of the 125 patients, 47 underwent unilateral
      adrenalectomy, while 78 patients were followed conservatively. These patients
      were reinvestigated after a mean follow-up time of 9.1 (5-16) years in 2006, with
      special emphasis on laboratory and other atherosclerotic risk factors (ARF),
      vascular events, and interventions. RESULTS: The prevalences of hypertension,
      impaired glucose tolerance or T2DM, hyperlipidemy, and obesity were 82, 43, 58,
      and 50%, and 89, 58, 82, and 50% at baseline and follow-up, respectively. None of
      the investigated ARF prevalences were different between patients treated and not
      treated with adrenalectomy, and between patients with and without subclinical
      Cushing's syndrome. The prevalences of angina pectoris, acute myocardial
      infarction, coronary, and peripheral arterial interventions or cerebrovascular
      stroke did not differ significantly between patients treated and not treated with
      adrenalectomy. CONCLUSION: Our study confirms previous investigations reporting
      markedly increased prevalences of various ARF in patients with NFAAs.
      Adrenalectomy performed in these patients failed to decrease the prevalence of
      ARF and atherosclerotic morbidity.

PMID- 19174534
TI  - Effect of testosterone replacement therapy on arterial stiffness in older
      hypogonadal men.
AB  - OBJECTIVE: To assess arterial stiffness in a cohort of hypogonadal males and to
      investigate the effect of testosterone replacement therapy on arterial properties
      in this specific group. DESIGN: Eighteen male patients with untreated acquired
      hypogonadism due to either adult-onset idiopathic hypogonadotropic hypogonadism
      (n=9) or pituitary tumor (n=9) and 12 age-, sex, and weight-matched eugonadal
      healthy controls were recruited for the study. Arterial properties, plasma
      glucose, lipid profile, total, and bioavailable testosterone (BT) levels were
      measured in fasting state. In the hypogonadal subjects, the effect of transdermal
      testosterone replacement therapy on arterial properties was studied by repeat
      noninvasive measurements at baseline, as well as 48 h and 90 days following the
      initiation of treatment. METHODS: Arterial stiffness was evaluated using
      applanation tonometry and pulse wave analysis by three different standard devices
      that assess various measures of arterial stiffness: pulse wave velocity (PWV),
      augmentation index (AIx), and large/small artery compliance (C1 and C2). RESULTS:
      Age- and blood pressure-adjusted PWV was significantly higher in hypogonadal men
      (8.90+/-2.29 vs 6.78+/-1.16 m/s in the control group; P=0.025). Testosterone
      therapy increased BT level from 2.01+/-1.04 to 4.68+/-2.43 and 7.83+/-6.2 nmol/l
      after 48 h and 3 months respectively (P=0.001). PWV decreased from 8.9+/-2.29 to
      8.24+/-1.39 and 8.25+/-1.82 m/s after 48 h and 3 months of treatment respectively
      (P=0.03). CONCLUSIONS: Male hypogonadism is associated with increased PWV, which
      is rapidly but incompletely ameliorated by normalization of circulating
      testosterone levels.

PMID- 19174535
TI  - Regulation of carotenoid composition and shoot branching in Arabidopsis by a
      chromatin modifying histone methyltransferase, SDG8.
AB  - Carotenoid pigments are critical for plant survival, and carotenoid composition
      is tuned to the developmental stage, tissue, and to environmental stimuli. We
      report the cloning of the CAROTENOID CHLOROPLAST REGULATORY1 (CCR1) gene. The
      ccr1 mutant has increased shoot branching and altered carotenoid composition,
      namely, reduced lutein in leaves and accumulation of cis-carotenes in dark-grown
      seedlings. The CCR1 gene was previously isolated as EARLY FLOWERING IN SHORT DAYS
      and encodes a histone methyltransferase (SET DOMAIN GROUP 8) that methylates
      histone H3 on Lys 4 and/or 36 (H3K4 and H3K36). ccr1 plants show reduced
      trimethyl-H3K4 and increased dimethyl-H3K4 surrounding the CAROTENOID ISOMERASE
      (CRTISO) translation start site, which correlates with low levels of CRTISO mRNA.
      Microarrays of ccr1 revealed the downregulation of 85 genes, including CRTISO and
      genes associated with signaling and development, and upregulation of just 28
      genes. The reduction in CRTISO transcript abundance explains the altered
      carotenoid profile. The changes in shoot branching are additive with more
      axillary branching mutants, but the altered carotenoid profile may partially
      affect shoot branching, potentially by perturbed biosynthesis of the carotenoid
      substrates of strigolactones. These results are consistent with SDG8 regulating
      shoot meristem activity and carotenoid biosynthesis by modifying the chromatin
      surrounding key genes, including CRTISO. Thus, the level of lutein, the most
      abundant carotenoid in higher plants that is critical for photosynthesis and
      photoprotection, appears to be regulated by a chromatin modifying enzyme in
      Arabidopsis thaliana.

PMID- 19174536
TI  - Emergence of enhanced attention to fearful faces between 5 and 7 months of age.
AB  - The adult brain is endowed with mechanisms subserving enhanced processing of
      salient emotional and social cues. Stimuli associated with threat represent one
      such class of cues. Previous research suggests that preferential allocation of
      attention to social signals of threat (i.e. a preference for fearful over happy
      facial expressions) emerges during the second half of the first year. The present
      study was designed to determine the age of onset for infants' attentional bias
      for fearful faces. Allocation of attention was studied by measuring event-related
      potentials (ERPs) and looking times (in a visual paired comparison task) to
      fearful and happy faces in 5- and 7-month-old infants. In 7-month-olds, the
      preferential allocation of attention to fearful faces was evident in both ERPs
      and looking times, i.e. the negative central mid-latency ERP amplitudes were more
      negative, and the looking times were longer for fearful than happy faces. No such
      differences were observed in the 5-month-olds. It is suggested that an enhanced
      sensitivity to facial signals of threat emerges between 5 and 7 months of age,
      and it may reflect functional development of the neural mechanisms involved in
      processing of emotionally significant stimuli.

PMID- 19174537
TI  - Anticipation of monetary and social reward differently activates mesolimbic brain
      structures in men and women.
AB  - Motivation for goal-directed behaviour largely depends on the expected value of
      the anticipated reward. The aim of the present study was to examine how different
      levels of reward value are coded in the brain for two common forms of human
      reward: money and social approval. To account for gender differences 16 male and
      16 female participants performed an incentive delay task expecting to win either
      money or positive social feedback. fMRI recording during the anticipation phase
      revealed proportional activation of neural structures constituting the human
      reward system for increasing levels of reward, independent of incentive type.
      However, in men activation in the prospect of monetary rewards encompassed a wide
      network of mesolimbic brain regions compared to only limited activation for
      social rewards. In contrast, in women, anticipation of either incentive type
      activated identical brain regions. Our findings represent an important step
      towards a better understanding of motivated behaviour by taking into account
      individual differences in reward valuation.

PMID- 19174538
TI  - Social capital and health care access: a systematic review.
AB  - There is a growing interest in community-level characteristics such as social
      capital and its relationship to health care access. To assess the rigor with
      which this construct has been empirically applied in research on health care
      access, a systematic review was conducted. A total of 2,396 abstracts were
      reviewed, and 21 met the criteria of examining some measure of social capital and
      its effects on health care access. The review found a lack of congruence in how
      social capital was measured and interpreted and a general inconsistency in
      findings, which made it difficult to draw firm conclusions about the effects of
      social capital on health care access. Insights from the social network literature
      can help improve the conceptual and measurement problems. Future work should
      distinguish among bonding, bridging, and linking social capital and their sources
      and benefits, and examine whether three dimensions of social capital actually
      exist: cognitive, behavioral, and structural.

PMID- 19174539
TI  - Essential and overlapping functions for mammalian Argonautes in microRNA
      silencing.
AB  - MicroRNA (miRNA) silencing fine-tunes protein output and regulates diverse
      biological processes. Argonaute (Ago) proteins are the core effectors of the
      miRNA pathway. In lower organisms, multiple Agos have evolved specialized
      functions for distinct RNA silencing pathways. However, the roles of mammalian
      Agos have not been well characterized. Here we show that mouse embryonic stem
      (ES) cells deficient for Ago1-4 are completely defective in miRNA silencing and
      undergo apoptosis. In miRNA silencing-defective ES cells, the proapoptotic
      protein Bim, a miRNA target, is increased, and up-regulation of Bim is sufficient
      to induce ES cell apoptosis. Expression of activated Akt inhibits Bim expression
      and partially rescues the growth defect in Ago-deficient ES cells. Furthermore,
      reintroduction of any single Ago into Ago-deficient cells is able to rescue the
      endogenous miRNA silencing defect and apoptosis. Consistent with this, each Ago
      is functionally equivalent with bulged miRNA duplexes for translational
      repression, whereas Ago1 and Ago2 appear to be more effective at utilizing
      perfectly matched siRNAs. Thus, our results demonstrate that mammalian Agos all
      contribute to miRNA silencing, and individual Agos have largely overlapping
      functions in this process.

PMID- 19174540
TI  - Commentary: Challenging public health orthodoxies--prophesy or heresy?

PMID- 19174541
TI  - Commentary: Individual, ecological and multilevel fallacies.

PMID- 19174542
TI  - Commentary: Chlamydia trachomatis screening: what are we trying to do?

PMID- 19174543
TI  - Commentary: The study by Leinsalu et al. on mortality differentials in Eastern
      Europe highlights the need for better data.

PMID- 19174544
TI  - Probing structure of heme A synthase from Bacillus subtilis by site-directed
      mutagenesis.
AB  - Biosynthesis of heme A from heme B is catalysed by two enzymes, heme O and heme A
      synthases, in the membrane. Heme A synthase in Bacillus subtilis (CtaA) has eight
      transmembrane helices and oxidizes a methyl group on pyrrole ring D of heme O to
      an aldehyde. In this study, to explore structure of heme binding site(s) in heme
      A synthase, we overproduced the B. subtilis His(6)-CtaA in Escherichia coli and
      characterized spectroscopic properties of the purified CtaA. On the contrary to a
      previous report (Svensson, B., Andersson, K.K., and Hederstedt, L. (1996) Low
      spin heme A in the heme A biosynthetic protein CtaA from Bacillus subtilis. Eur.
      J. Biochem. 238, 287-295), we found that two molecules of heme B were bound to
      CtaA. Further, we demonstrated that substitutions of His60 and His126 did not
      affect heme binding while His216 and His278 in the carboxy-halves are essential
      in heme binding. And we found that Ala substitutions of Cys191 and Cys197 in loop
      5/6 reduced heme content to a half of the wild-type level. On the basis of our
      findings, we proposed a helical-wheel-projection model of CtaA.

PMID- 19174545
TI  - Maturation of the extracellular matrix and cell adhesion molecules in layered co
      cultures of HepG2 and endothelial cells.
AB  - We previously reported that using thermo-responsive culture surfaces, a layered
      co-culture was achieved by placing an endothelial cell sheet onto a layer of
      human hepatoma cell line HepG2 in order to develop a culture model that mimics
      hepatic lobules. In the layered co-culture cells, the expression levels of liver
      specific genes gradually increased. A cross-sectional view of the layered co
      culture cells showed that the thickness of the layer slowly increased after
      layering, as did extracellular matrix (ECM) deposition around HepG2 cells. In
      this study, we report that the molecular compositions of ECM and cell-adhesion
      molecules changed in the layered co-culture cells. Gene expression of integrin
      alpha4 and decorin gradually increased after layering, and the time-course
      pattern of these genes was correlated with that of liver-specific genes.
      Moreover, the layered co-culture system has the ability to assemble a branching
      network of fibronectin fibrils. These results suggest that a vastly different
      extracellular environment in layered co-culture cells may induce an increase in
      liver-specific functions.

PMID- 19174546
TI  - Effects of replacement of low-spin haem b by haem O on Escherichia coli
      cytochromes bo and bd quinol oxidases.
AB  - Cytochromes bo and bd are terminal ubiquinol oxidases in the aerobic respiratory
      chain of Escherichia coli and generate proton motive force across the membrane.
      To probe roles of haem species in the oxidation of quinols, intramolecular
      electron transfer and the dioxygen reduction, we replaced b-haems with haem O by
      using the haem O synthase-overproducing system, which can accumulate haem O in
      cytoplasmic membranes. Characterizations of spectroscopic properties of
      cytochromes bo and bd isolated from BL21 (DE3)/pLysS and BL21 (DE3)/pLysS/pTTQ18
      cyoE after 4 h of the aerobic induction of haem O synthase (CyoE) showed the
      specific incorporation of haem O into the low-spin haem-binding site in both
      oxidases. We found that the resultant haem oo- and obd-type oxidase severely
      reduced the ubiquinol-1 oxidase activity due to the perturbations of the quinol
      oxidation site. Our observations suggest that haem B is required at the low-spin
      haem site for the oxidation of quinols by cytochromes bo and bd.

PMID- 19174547
TI  - Impaired chemotaxis and cell adhesion due to decrease in several cell-surface
      receptors in cathepsin E-deficient macrophages.
AB  - Cathepsin E is an endo-lysosomal aspartic proteinase exclusively present in
      immune system cells. Previous studies have shown that cathepsin E-deficient
      (CatE(-/-)) mice display aberrant immune responses such as atopic dermatitis and
      higher susceptibility to bacterial infection. However, the mechanisms underlying
      abnormal immune responses induced by cathepsin E deficiency are still unclear. In
      this study, we found that the cell-surface levels of chemotactic receptors,
      including chemokine receptor (CCR)-2 and N-formyl peptide receptors (FPRs), were
      clearly diminished in CatE(-/-)macrophages compared with those in wild-type
      cells. Consistently, chemotaxis of CatE(-/-)macrophages to MCP-1 and N-formyl
      methionyl-leucyl-phenylalanine was also decreased. Similar to the chemotactic
      receptors, the surface expressions of the adhesion receptors CD18 (integrin
      beta(2)) and CD 29 (integrin beta(1)) in CatE(-/-) macrophages were significantly
      decreased, thereby reducing cell attachment of CatE(-/-) macrophages. These
      results indicate that the defects in chemotaxis and cell adhesion are likely to
      be involved in the imperfect function of CatE(-/-)macrophages.

PMID- 19174548
TI  - Gender disparity of hepatic lipid homoeostasis regulated by the circadian clock.
AB  - The mammalian clock regulates major aspects of energy metabolism, including
      glucose and lipid homoeostasis as well as mitochondrial oxidative metabolism.
      This study is to identify specific patterns of circadian rhythms for lipid
      homoeostasis in both female and male mouse livers, and to clarify gender
      disparity in coupling the peripheral circadian clock to lipid metabolic outputs
      by nuclear receptors. To achieve this, profiling the diurnal hepatic expression
      of genes encoding circadian clocks, nuclear receptors and lipid metabolic enzymes
      was performed. Hepatic lipid levels including cholesterol, triglyceride and non
      esterified fatty acids (NEFAs) were monitored over a 24-h period. The cosinor
      analysis revealed that several genes encoding nuclear receptors and enzymes
      involved in the lipid metabolic pathway were rhythmically expressed in liver in
      phase with the peripheral clocks, which were correlated with the diurnal changes
      of hepatic lipid levels. Gender disparity was observed for circadian
      characteristics including mesor and amplitude values, accompanied with advances
      in acrophases in female mouse livers. Accordingly, gender differences were also
      observed in diurnal lipid homoeostasis. The identification of cycling patterns
      for lipid metabolic pathways in both female and male mouse livers may shed light
      on the development of gender-based treatment for human diseases related to the
      coordination of the cellular clock and control of lipid homoeostasis.

PMID- 19174549
TI  - Two crystal structures of lysyl-tRNA synthetase from Bacillus stearothermophilus
      in complex with lysyladenylate-like compounds: insights into the irreversible
      formation of the enzyme-bound adenylate of L-lysine hydroxamate.
AB  - Aminoacyl-tRNA synthetase forms an enzyme-bound intermediate, aminoacyladenylate
      in the amino-acid activation reaction. This reaction is monitored by measuring
      the ATP-PPi exchange reason in which [(32)P]PPi is incorporated into ATP. We
      previously reported that L-lysine hydroxamate completely inhibited the L-lysine
      dependent ATP-PPi exchange reaction catalysed by lysyl-tRNA synthetase from
      Bacillus stearothermophilus (BsLysRS). Several experiments suggested that BsLysRS
      can adenylate L-lysine hydroxamate, but the enzyme-bound lysyladenylate-like
      compound does not undergo the nucleophilic attack of PPi. This contrasts with the
      two reports for seryl-tRNA synthetase (SerRS): (i) L-serine hydroxamate was
      utilized by yeast SerRS as a substrate in the ATP-PPi exchange; and (ii) a
      seryladenylate-like compound was formed from L-serine hydroxamate in the crystal
      structure of Thermus thermophilus SerRS. To gain clues about the mechanistic
      difference, we have determined the crystal structures of two complexes of BsLysRS
      with the adenylate of L-lysine hydroxamate and with 5'-O-[N-(L-Lysyl)sulphamoyl]
      adenosine. The comparisons of the two BsLysRS structures and the above SerRS
      structure revealed the specific side-chain shift of Glu411 of BsLysRS in the
      complex with the adenylate of L-lysine hydroxamate. In support of other
      structural comparisons, the result suggested that Glu411 plays a key role in the
      arrangement of PPi for the nucleophilic attack.

PMID- 19174550
TI  - Changing hormone levels during the menstrual cycle affect knee laxity and
      stiffness in healthy female subjects.
AB  - BACKGROUND: Whether knee laxity varies throughout the menstrual cycle remains
      controversial. As increased laxity may be a risk factor for anterior cruciate
      ligament (ACL) injury, further research is warranted. HYPOTHESIS: Variation in
      estradiol and progesterone levels during the menstrual cycle influences knee
      laxity and stiffness. STUDY DESIGN: Case control study; Level of evidence, 3.
      METHODS: The serum estradiol and progesterone levels of 26 healthy female
      subjects were recorded in the follicular phase, ovulation, and the luteal phase.
      Knee joint laxity was assessed using a standard knee arthrometer at the same
      intervals. Stiffness changes in the load-displacement curve were determined.
      Hormone levels across the cycle were compared between responders and
      nonresponders, defined by whether changes in knee laxity at 89 N occurred.
      RESULTS: Greater laxity at 89 N during ovulation was observed (ovulation: 5.13 +/
      1.70 mm vs luteal: 4.55 +/- 1.54 mm, P = .012). In knee laxity testing at manual
      maximum load, greater laxity was noticed during ovulation (14.43 +/- 2.60 mm, P =
      .018), as compared with the follicular phase (13.35 +/- 2.53 mm). A reduction in
      knee stiffness of approximately 17% (ovulation: 12.48 +/- 5.46 N/mm vs luteal:
      15.02 +/- 7.71 N/mm, P = .042) during ovulation was observed. However, there were
      no differences in hormone levels between responders and nonresponders at 89 N.
      CONCLUSION: Female hormone levels are related to increased knee joint laxity and
      decreased stiffness at ovulation. To understand subject variations in knee joint
      laxity during the menstrual cycle in female athletes, further investigation is
      warranted.

PMID- 19174551
TI  - Biceps activity during windmill softball pitching: injury implications and
      comparison with overhand throwing.
AB  - BACKGROUND: Windmill pitching produces high forces and torques at the shoulder
      and elbow, making the biceps labrum complex susceptible to overuse injury. Little
      is known about the muscle firing patterns during a windmill pitch. HYPOTHESIS:
      Biceps muscle activity is greater during a windmill pitch than during an overhand
      throw. STUDY DESIGN: Descriptive laboratory study. METHODS: Seven female windmill
      pitchers underwent motion analysis and surface electromyography evaluation of
      their biceps muscles during windmill and overhand throwing. Marker motion
      analysis, muscle activity, and ball release were captured simultaneously. Surface
      electromyography trials were collected and related to the athletes' phases of
      pitching and throwing, identified based on predefined softball and baseball
      pitching mechanics. RESULTS: Throws were of similar velocity (24 m/s, 53 mph, P =
      .71), but peak biceps brachii muscle activation during the windmill pitch was
      significantly greater than during the overhand throw when normalized (38% vs 19%
      manual muscle test, P = .02). The highest muscle activity occurred at the 9
      o'clock phase of the windmill pitch, during which the biceps brachii undergoes
      eccentric contraction. In the overhand throw, the highest level of biceps
      activity occurred during arm cocking. CONCLUSION: In female athletes, biceps
      brachii activity during the windmill pitch is higher than during an overhand
      throw and is most active during the 9-o'clock and follow-through phases of the
      pitch. CLINICAL RELEVANCE: Repetitive eccentric biceps contractions may help
      explain the high incidence of anterior shoulder pain clinically observed in elite
      windmill pitchers. Injury prevention and treatment mechanisms should focus on the
      phases with the highest muscle activity.

PMID- 19174552
TI  - Discovery of ixabepilone.
AB  - The discovery of the antineoplastic agent paclitaxel and its unique activity as a
      microtubule-stabilizing agent resulted in dramatic improvements in the treatment
      of breast, ovarian, and non-small cell lung cancers. Despite the potent antitumor
      activity of taxanes such as paclitaxel, efficacy of these agents has been limited
      by development of taxane-resistant tumors in patients. This review describes,
      with some historical context, our successful efforts to discover a next
      generation microtubule-stabilizing agent for the treatment of cancer. In
      collaboration with the Gesellschaft fur Biotechnologische Forschung, we evaluated
      the epothilones, originally isolated from the myxobacterium Sorangium cellulosum,
      as potential anticancer agents. Experiments performed at Bristol-Myers Squibb
      confirmed the ability of these agents to induce tubulin polymerization, cell
      cycle arrest, and apoptosis. Epothilones A and B showed potent cytotoxic activity
      toward paclitaxel-sensitive and paclitaxel-resistant cells expressing P
      glycoprotein or mutant tubulin. Because the parent epothilones were subject to
      inactivation via esterase cleavage, we used semisynthetic approaches to prepare
      analogues without this liability. BMS-247550 (ixabepilone), the lactam analogue
      of epothilone B, showed increased metabolic stability, potent tubulin
      polymerization activity, and retained activity against paclitaxel-resistant
      lines. Based on its shown efficacy in clinical trials, ixabepilone was approved
      by the Food and Drug Administration in 2007 for treatment of drug
      resistant/refractory metastatic or locally advanced breast cancer.

PMID- 19174553
TI  - A direct pancreatic cancer xenograft model as a platform for cancer stem cell
      therapeutic development.
AB  - There is an enormous gap between the antiproliferative and in vivo antitumor
      efficacy of gemcitabine in cell line-based models and its clinical efficacy. This
      may be due to insensitiveness of the precursor, cancer stem cell (CSC)
      compartment to cytotoxic agents. The hedgehog pathway is associated with CSC
      signaling and control. We used a direct xenograft model of pancreatic cancer and
      a two-stage approach was used to test the hypotheses that targeting CSC could
      increase the efficacy of gemcitabine. Tumors from a gemcitabine-sensitive
      xenograft were treated with gemcitabine first, and randomized, after tumor
      regression to continuing treatment with gemcitabine, a hedgehog inhibitor alone
      or in combination with gemcitabine. We tested markers described as associated
      with CSC such as CD24, CD44, ALDH, nestin, and the hedgehog pathway. After
      induction with gemcitabine, treated tumor showed an enrichment in CSC markers
      such as ALDH and CD24. Subsequently, a release from gemcitabine prompted a
      repopulation of proliferating cells and a decrease in such markers to equilibrate
      from pretreatment levels. Combined treatment with gemcitabine and cyclopamine
      induced tumor regression and decrease in CSC markers and hedgehog signaling.
      Cytoplasmic CD24 and ALDH were inversely and strongly associated with growth and
      were expressed in a minority of cells that we propose constitute the CSC
      compartment. Hedgehog inhibitors as part of a dual compartment therapeutic
      approach were able to further reduce tumor growth and decreased both static and
      dynamic markers of CSC. Direct tumor xenografts are a valid platform to test
      multicompartment therapeutic approaches in pancreatic cancer.

PMID- 19174554
TI  - Mapatumumab and lexatumumab induce apoptosis in TRAIL-R1 and TRAIL-R2 antibody
      resistant NSCLC cell lines when treated in combination with bortezomib.
AB  - Mapatumumab and lexatumumab are fully human monoclonal antibodies that bind and
      activate human tumor necrosis factor-related apoptosis-inducing ligand receptors
      1 and 2, respectively. These antibodies induce apoptosis in various tumor cell
      types, although the degree of sensitivity can vary from highly sensitive to
      completely resistant. Importantly, tumor cells that are partially or completely
      resistant to mapatumumab or lexatumumab can often be sensitized when treated in
      combination with chemotherapeutic drugs. In this regard, the proteasome inhibitor
      bortezomib has recently shown synergistic activity against established lymphoma
      cell lines and primary lymphomas when combined with mapatumumab and lexatumumab.
      Here, we report similar findings using a panel of human non-small cell lung
      cancer (NSCLC) cell lines. Specifically, we show that bortezomib rapidly induces
      sensitivity to mapatumumab and lexatumumab in NSCLC cell lines that are
      completely resistant to antibody alone and that bortezomib concentrations as low
      as 25 nmol/L sensitize NSCLC cells to the antibodies. Furthermore, bortezomib at
      the tested concentration has minimal effect on its own, indicating the
      combination generates synergistic cytotoxicity. Combination treatment induces
      activation of the caspase cascade and the effect of the combination is caspase
      dependent. Bortezomib treatment increases the intracellular levels of several
      important apoptosis regulators that may mediate enhanced sensitivity to
      mapatumumab and lexatumumab. These results suggest future evaluation of
      mapatumumab or lexatumumab in combination with bortezomib is warranted in NSCLC
      patients.

PMID- 19174555
TI  - Biological characterization of AT7519, a small-molecule inhibitor of cyclin
      dependent kinases, in human tumor cell lines.
AB  - Cyclin-dependent kinases (CDK), and their regulatory cyclin partners, play a
      central role in eukaryotic cell growth, division, and death. This key role in
      cell cycle progression, as well as their deregulation in several human cancers,
      makes them attractive therapeutic targets in oncology. A series of CDK inhibitors
      was developed using Astex's fragment-based medicinal chemistry approach, linked
      to high-throughput X-ray crystallography. A compound from this series, designated
      AT7519, is currently in early-phase clinical development. We describe here the
      biological characterization of AT7519, a potent inhibitor of several CDK family
      members. AT7519 showed potent antiproliferative activity (40-940 nmol/L) in a
      panel of human tumor cell lines, and the mechanism of action was shown here to be
      consistent with the inhibition of CDK1 and CDK2 in solid tumor cell lines. AT7519
      caused cell cycle arrest followed by apoptosis in human tumor cells and inhibited
      tumor growth in human tumor xenograft models. Tumor regression was observed
      following twice daily dosing of AT7519 in the HCT116 and HT29 colon cancer
      xenograft models. We show that these biological effects are linked to inhibition
      of CDKs in vivo and that AT7519 induces tumor cell apoptosis in these xenograft
      models. AT7519 has an attractive biological profile for development as a clinical
      candidate, and the tolerability and efficacy in animal models compare favorably
      with other CDK inhibitors in clinical development. Studies described here formed
      the biological rationale for investigating the potential therapeutic benefit of
      AT7519 in cancer patients.

PMID- 19174556
TI  - WIF1, a Wnt pathway inhibitor, regulates SKP2 and c-myc expression leading to G1
      arrest and growth inhibition of human invasive urinary bladder cancer cells.
AB  - Epigenetic silencing of secreted wingless-type (Wnt) antagonists through
      hypermethylation is associated with tobacco smoking and with invasive bladder
      cancer. The secreted Wnt inhibitory factor-1 (WIF1) has shown consistent growth
      inhibitory effect on various cancer cell lines. Therefore, we assessed the
      mechanisms of action of WIF1 by either restoring WIF1 expression in invasive
      bladder cancer cell lines (T24 and TSU-PR1) or using a recombinant protein
      containing functional WIF1 domain. Both ectopic expression of WIF1 and treatment
      with WIF1 domain protein resulted in cell growth inhibition via G(1) arrest. The
      G(1) arrest induced by WIF1 is associated with down-regulation of SKP2 and c-myc
      and up-regulation of p21/WAF1 and p27/Kip1. Conversely, reexpression of SKP2 in
      WIF1-overexpressing TSU-PR1 cells attenuated the WIF1-induced G(1) arrest.
      Furthermore, inhibition of nuclear Wnt signaling by either dominant-negative LEF1
      or short hairpin RNA of TCF4 also reduced SKP2 expression. The human SKP2 gene
      contains two TCF/LEF1 consensus binding sites within the promoter. Chromatin
      immunoprecipitation/real-time PCR analysis revealed that both WIF1 and dominant
      negative LEF1 expression decreased the in vivo binding of TCF4 and beta-catenin
      to the SKP2 promoter. Together, our results suggest that mechanisms of WIF1
      induced G(1) arrest include (a) SKP2 down-regulation leading to p27/Kip1
      accumulation and (b) c-myc down-regulation releasing p21/WAF1 transcription.
      Additionally, we show that WIF1 inhibits in vivo bladder tumor growth in nude
      mice. These observations suggest a mechanism for transformation of bladder
      epithelium on loss of WIF1 function and provide new targets such as SKP2 for
      intervention in WIF1-deficient bladder cancer.

PMID- 19174557
TI  - Effective sensitization of temozolomide by ABT-888 is lost with development of
      temozolomide resistance in glioblastoma xenograft lines.
AB  - Resistance to temozolomide and radiotherapy is a major problem for patients with
      glioblastoma but may be overcome using the poly(ADP-ribose) polymerase inhibitor
      ABT-888. Using two primary glioblastoma xenografts, the efficacy of ABT-888
      combined with radiotherapy and/or temozolomide was evaluated. Treatment with ABT
      888 combined with temozolomide resulted in significant survival prolongation
      (GBM12: 55.1%, P = 0.005; GBM22: 54.4%, P = 0.043). ABT-888 had no effect with
      radiotherapy alone but significantly enhanced survival in GBM12 when combined
      with concurrent radiotherapy/temozolomide. With multicycle therapy, ABT-888
      further extended the survival benefit of temozolomide in the inherently sensitive
      GBM12 and GBM22 xenograft lines. However, after in vivo selection for
      temozolomide resistance, the derivative GBM12TMZ and GBM22TMZ lines were no
      longer sensitized by ABT-888 in combination with temozolomide, and a similar lack
      of efficacy was observed in two other temozolomide-resistant tumor lines. Thus,
      the sensitizing effects of ABT-888 were limited to tumor lines that have not been
      previously exposed to temozolomide, and these results suggest that patients with
      newly diagnosed glioblastoma may be more likely to respond to combined
      temozolomide/poly(ADP-ribose) polymerase inhibitor therapy than patients with
      recurrent disease.

PMID- 19174558
TI  - Dihydroorotate dehydrogenase inhibitor A771726 (leflunomide) induces apoptosis
      and diminishes proliferation of multiple myeloma cells.
AB  - Multiple myeloma is still an incurable disease; therefore, new therapeutics are
      urgently needed. A771726 is the active metabolite of the immunosuppressive drug
      leflunomide, which is currently applied in the treatment of rheumatoid arthritis,
      BK virus nephropathy, and cytomegaly viremia. Here, we show that dihydroorotate
      dehydrogenase (DHODH) is commonly expressed in multiple myeloma cell lines and
      primary multiple myeloma cells. The DHODH inhibitor A771726 inhibits cell growth
      in common myeloma cell lines at clinically achievable concentrations in a time-
      and dose-dependent manner. Annexin V-FITC/propidium iodide staining revealed
      induction of apoptosis of multiple myeloma cell lines and primary multiple
      myeloma cells. The 5-bromo-2'-deoxyuridine cell proliferation assay showed that
      inhibition of cell growth was partly due to inhibition of multiple myeloma cell
      proliferation. A771726 induced G(1) cell cycle arrest via modulation of cyclin D2
      and pRb expression. A771726 decreased phosphorylation of protein kinase B (Akt),
      p70S6K, and eukaryotic translation initiation factor 4E-binding protein-1 as
      shown by Western blotting experiments. Furthermore, we show that the stimulatory
      effect of conditioned medium of HS-5 bone marrow stromal cells on multiple
      myeloma cell growth is completely abrogated by A771726. In addition, synergism
      studies revealed synergistic and additive activity of A771726 together with the
      genotoxic agents melphalan, treosulfan, and doxorubicin as well as with
      dexamethasone and bortezomib. Taken together, we show that inhibition of DHODH by
      A771726/leflunomide is effective in multiple myeloma. Considering the favorable
      toxicity profile and the great clinical experience with leflunomide in rheumatoid
      arthritis, this drug represents a potential new candidate for targeted therapy in
      multiple myeloma.

PMID- 19174559
TI  - Inhibition of cervical cancer cell growth by human papillomavirus virus-like
      particles packaged with human papillomavirus oncoprotein short hairpin RNAs.
AB  - Overexpression of human papillomavirus (HPV E6 and HPV E7) oncogenes in human
      cervical cells results in the development of cancer, and E6 and E7 proteins are
      therefore targets for preventing cervical cancer progression. Here, we describe
      the silencing of E6 and E7 expression in cervical carcinoma cells by RNA
      interference. In order to increase the efficacy of the RNA interference, HPV
      pseudovirions coding for a short hairpin RNA (shRNA) sequence were produced. The
      results indicated the degradation of E6 and E7 mRNAs when shRNA against E6 or E7
      were delivered by pseudovirions in HPV-positive cells (CaSki and TC1 cells). E6
      silencing resulted in the accumulation of cellular p53 and reduced cell
      viability. More significant cell death was observed when E7 expression was
      suppressed. Silencing E6 and E7 and the consequences for cancer cell growth were
      also investigated in vivo in mice using the capacity of murine TC1 cells
      expressing HPV-16 E6 and E7 oncogenes to induce fast-growing tumors. Treatment
      with lentiviruses and HPV virus-like particle vectors coding for an E7 shRNA
      sequence both resulted in dramatic inhibition of tumor growth. These results show
      the ability of pseudovirion-delivered shRNA to produce specific gene suppression
      and provide an effective means of reducing HPV-positive tumor growth.

PMID- 19174560
TI  - Vorinostat and bortezomib exert synergistic antiproliferative and proapoptotic
      effects in colon cancer cell models.
AB  - Despite the availability of several Food and Drug Administration-approved drugs,
      advanced inoperable colorectal cancer remains incurable. In this study, we
      focused on the development of combined molecular targeted therapies against colon
      cancer by testing the efficacy of the combination of the histone deacetylase
      inhibitor vorinostat with the proteasome inhibitor bortezomib to determine if
      this resulted in synergistic antitumor effects against colorectal cancer. The
      effects of the histone deacetylase inhibitor vorinostat in combination with the
      proteasome inhibitor bortezomib on the growth of two colorectal cancer cell lines
      were assessed with regard to proliferation, cell cycle arrest, and apoptosis.
      Treatment with the combination of vorinostat and bortezomib resulted in a
      synergistic decrease in proliferation of both colorectal cancer cell lines
      compared with treatment with single agents alone. This inhibition was associated
      with a synergistic increase in apoptosis as measured by caspase-3/7 activity and
      cleaved poly(ADP-ribose) polymerase. In addition, we observed an increase in the
      proapoptotic protein BIM and in the number of cells arrested in the G(2)-M phase
      of the cell cycle. Although p21 levels were significantly increased, short
      hairpin RNA knockdown of p21 did not lead to changes in proliferation in response
      to the combination of drugs, indicating that although p21 is a target of these
      drugs, it is not required to mediate their antiproliferative effects. These data
      indicate that combination treatment with vorinostat and bortezomib result in
      synergistic antiproliferative and proapoptotic effects against colon cancer cell
      lines, providing a rational basis for the clinical use of this combination for
      the treatment of colorectal cancer.

PMID- 19174561
TI  - Molecular dissection of translation termination mechanism identifies two new
      critical regions in eRF1.
AB  - Translation termination in eukaryotes is completed by two interacting factors
      eRF1 and eRF3. In Saccharomyces cerevisiae, these proteins are encoded by the
      genes SUP45 and SUP35, respectively. The eRF1 protein interacts directly with the
      stop codon at the ribosomal A-site, whereas eRF3-a GTPase protein-probably acts
      as a proofreading factor, coupling stop codon recognition to polypeptide chain
      release. We performed random PCR mutagenesis of SUP45 and screened the library
      for mutations resulting in increased eRF1 activity. These mutations led to the
      identification of two new pockets in domain 1 (P1 and P2) involved in the
      regulation of eRF1 activity. Furthermore, we identified novel mutations located
      in domains 2 and 3, which confer stop codon specificity to eRF1. Our findings are
      consistent with the model of a closed-active conformation of eRF1 and shed light
      on two new functional regions of the protein.

PMID- 19174562
TI  - Mutually exclusive STAT1 modifications identified by Ubc9/substrate dimerization
      dependent SUMOylation.
AB  - Post-translational modifications control the physiological activity of the signal
      transducer and activator of transcription STAT1. While phosphorylation at
      tyrosine Y701 is a prerequisite for STAT1 dimerization, its SUMOylation represses
      the transcriptional activity. Recently, we have demonstrated that SUMOylation at
      lysine K703 inhibits the phosphorylation of nearby localized Y701 of STAT1. Here,
      we analysed the influence of phosphorylation of Y701 on SUMOylation of K703 in
      vivo. For that reason, an Ubc9/substrate dimerization-dependent SUMOylation
      (USDDS) system was developed, which consists of fusions of the SUMOylation
      substrate and of the SUMO-conjugating enzyme Ubc9 to the chemically activatable
      heterodimerization domains FKBP and FRB, respectively. When FKBP fusion proteins
      of STAT1, p53, CRSP9, FOS, CSNK2B, HES1, TCF21 and MYF6 are coexpressed with Ubc9
      FRB, treatment of HEK293 cells with the rapamycin-related dimerizer compound
      AP21967 induces SUMOylation of these proteins in vivo. For STAT1-FKBP and p53
      FKBP we show that this SUMOylation takes place at their specific SUMOylation
      sites in vivo. Using USDDS, we then demonstrate that STAT1 phosphorylation at
      Y701 induced by interferon-beta treatment inhibits SUMOylation of K703 in vivo.
      Thus, pY701 and SUMO-K703 of STAT1 represent mutually exclusive modifications,
      which prevent signal integration at this molecule and probably ensure the
      existence of differentially modified subpopulations of STAT1 necessary for its
      regulated nuclear cytoplasmic activation/inactivation cycle.

PMID- 19174563
TI  - Improved tetracycline repressors for gene silencing in mycobacteria.
AB  - Tetracycline repressor (TetR)-controlled expression systems have recently been
      developed for mycobacteria and proven useful for the construction of conditional
      knockdown mutants and their analysis in vitro and during infections. However,
      even though these systems allowed tight regulation of some mycobacterial genes,
      they only showed limited or no phenotypic regulation for others. By adapting
      their codon usage to that of the Mycobacterium tuberculosis genome, we created
      tetR genes that mediate up to approximately 50-fold better repression of reporter
      gene activities in Mycobacterium smegmatis and Mycobacterium bovis BCG. In
      addition to these repressors, for which anhydrotetracycline (atc) functions as an
      inducer of gene expression, we used codon-usage adaption and structure-based
      design to develop improved reverse TetRs, for which atc functions as a
      corepressor. The previously described reverse repressor TetR only functioned when
      expressed from a strong promoter on a multicopy plasmid. The new reverse TetRs
      silence target genes more efficiently and allowed complete phenotypic silencing
      of M. smegmatis secA1 with chromosomally integrated tetR genes.

PMID- 19174564
TI  - Structural insights into TDP-43 in nucleic-acid binding and domain interactions.
AB  - TDP-43 is a pathogenic protein: its normal function in binding to UG-rich RNA is
      related to cystic fibrosis, and inclusion of its C-terminal fragments in brain
      cells is directly linked to frontotemporal lobar degeneration (FTLD) and
      amyotrophic lateral sclerosis (ALS). Here we report the 1.65 A crystal structure
      of the C-terminal RRM2 domain of TDP-43 in complex with a single-stranded DNA. We
      show that TDP-43 is a dimeric protein with two RRM domains, both involved in DNA
      and RNA binding. The crystal structure reveals the basis of TDP-43's TG/UG
      preference in nucleic acids binding. It also reveals that RRM2 domain has an
      atypical RRM-fold with an additional beta-strand involved in making protein
      protein interactions. This self association of RRM2 domains produced thermal
      stable RRM2 assemblies with a melting point greater than 85 degrees C as
      monitored by circular dichroism at physiological conditions. These studies thus
      characterize the recognition between TDP-43 and nucleic acids and the mode of
      RRM2 self association, and provide molecular models for understanding the role of
      TDP-43 in cystic fibrosis and the neurodegenerative diseases related to TDP-43
      proteinopathy.

PMID- 19174566
TI  - The use of fish oil in the community: results of a population-based study.

PMID- 19174565
TI  - The formation of double-strand breaks at multiply damaged sites is driven by the
      kinetics of excision/incision at base damage in eukaryotic cells.
AB  - It has been stipulated that repair of clustered DNA lesions may be compromised,
      possibly leading to the formation of double-strand breaks (DSB) and, thus, to
      deleterious events. Using a variety of model multiply damaged sites (MDS), we
      investigated parameters that govern the formation of DSB during the processing of
      MDS. Duplexes carrying MDS were inserted into replicative or integrative vectors,
      and used to transform yeast Saccharomyces cerevisiae. Formation of DSB was
      assessed by a relevant plasmid survival assay. Kinetics of excision/incision and
      DSB formation at MDS was explored using yeast cell extracts. We show that MDS
      composed of two uracils or abasic sites, were rapidly incised and readily
      converted into DSB in yeast cells. In marked contrast, none of the MDS carrying
      opposed oG and hU separated by 3-8 bp gave rise to DSB, despite the fact that
      some of them contained preexisting single-strand break (a 1-nt gap).
      Interestingly, the absence of DSB formation in this case correlated with slow
      excision/incision rates of lesions. We propose that the kinetics of the initial
      repair steps at MDS is a major parameter that direct towards the conversion of
      MDS into DSB. Data provides clues to the biological consequences of MDS in
      eukaryotic cells.

PMID- 19174567
TI  - Diffusion tensor anisotropy magnetic resonance imaging: a new tool to assess
      synovial inflammation.
AB  - OBJECTIVE: Diffusion tensor imaging (DTI) has been used to study the structure of
      ordered biological tissue. DTI-derived metrics correlate with inflammatory
      cytokines and adhesion molecules, expressed in the brain abscess. We aimed to
      study the role of DTI-derived metrics in delineating the synovitis and their
      correlation with inflammatory proteins expressed in the SF of chronic
      inflammatory arthritis patients. METHODS: DTI was performed on 18 patients and 6
      healthy controls. A follow-up DTI at 6 months was performed in 10 patients.
      Quantification of inflammatory cytokines (TNF-alpha, IL-1beta) and soluble
      intercellular adhesion molecule-1 (sICAM-1) in SF and their correlation with DTI
      derived metrics was performed. RESULTS: DTI-derived metrics, fractional
      anisotropy (FA), cylindrical isotropy (CL), planar anisotropy (CP) and spherical
      isotropy (CS), were significantly altered in the inflamed synovium of the
      patients as compared to the healthy controls. Significant correlation between FA
      and TNF-alpha (r = 0.68, P = 0.002) and IL-1beta (r = 0.48, P < 0.05) and inverse
      correlations between mean diffusivity (MD) and TNF-alpha (r = -0.54, P < 0.05)
      and CS and TNF-alpha (r = -0.53, P < 0.05) and CP and IL-1beta and sICAM (r =
      0.48, P < 0.05 and r = 0.49, P < 0.05, respectively) were observed. A significant
      correlation between post-contrast signal intensity (PCI) and IL-1beta and sICAM-1
      (r = 0.61, P = 0.01 and r = 0.46, P = 0.05) and volume and sICAM-1 (r = 0.45, P =
      0.05) was observed, respectively. CONCLUSION: Results of this pilot study suggest
      that the DTI-derived metrics have the potential to delineate synovial
      inflammation; however, it is not superior to conventional MRI for its detection
      and assessment of therapeutic response.

PMID- 19174568
TI  - A case of immune reconstitution syndrome: adult-onset Still's disease in a
      patient with HIV infection.

PMID- 19174569
TI  - The 'gout' of the Medici, Grand Dukes of Florence: a palaeopathological study.
AB  - OBJECTIVE: According to the written sources several members of the famous Medici
      family of Renaissance Florence suffered from an arthritic disease, called 'gout'
      by contemporary physicians; a palaeopathological study allowed verification of
      the true nature of the 'gout of the Medici' referred by archive document data.
      METHODS: The skeletal remains of the Grand Dukes and their families, buried in
      the Basilica of San Lorenzo in Florence, were examined macroscopically and
      submitted to X-ray investigation. RESULTS: Out of 15 investigated individuals,
      two cases of diffuse idiopathic skeletal hyperostosis (DISH), with ossification
      of the anterior longitudinal ligament and massive hyperostotic changes of the
      extra-spinal ligaments, were detected in the skeletons of the Grand Dukes Cosimo
      I (1519-74) and his son Ferdinand I (1549-1609). The left foot of Ferdinand also
      revealed typical lesions of the uratic gout, confirming the archive data, which
      describe the disease in detail. CONCLUSIONS: The association between DISH and
      elite status, highlighted in recent research, receives further confirmation in
      the present study, furnishing evidence to the significance of this disorder as a
      lifestyle indicator, linked specifically with a high-caloric diet, consequent
      obesity and type II diabetes mellitus. Furthermore, the coexistence between DISH
      and gout observed in Ferdinand represents the first documentation of this
      association in the palaeopathological literature.

PMID- 19174570
TI  - British Society for Rheumatology and British Health Professionals in Rheumatology
      guideline for the management of rheumatoid arthritis (after the first 2 years).

PMID- 19174572
TI  - Snails in bottles and language cuckoos: an evaluation of patient information
      resources for South Asians with osteomalacia.
AB  - OBJECTIVE: To assess the acceptability for use of information on osteomalacia for
      South Asian patients. METHODS: Ten focus groups of South Asian persons speaking
      Bengali, Gujarati, Hindi, Punjabi and Urdu (one male and one female group for
      each language) were used to evaluate the written (leaflets) and spoken
      information (CD) on osteomalacia for South Asian patients produced by the
      Arthritis Research Campaign (ARC). Focus group discussion was facilitated by
      community-based workers using the Social Action Research Method. A subsidiary
      evaluation of the information was conducted by a questionnaire-based survey sent
      to British Society of Rheumatology/British Health Professionals in Rheumatology
      (BSR/BHPR) members and others who had requested such materials from ARC in the
      past. RESULTS: Evaluation by focus groups revealed that there were potential
      difficulties relating to the understanding of the information leaflets and CDs
      and problematic issues regarding the quality of translation and pronunciation.
      Evaluation by BSR/BHPR members and others who had requested such material was
      that although the information was culturally appropriate, there were some weak
      areas such as mispronunciation, the quality of translation and specific customs.
      CONCLUSION: Healthcare information resources for minority ethnic groups has
      traditionally been developed depending upon the needs of the community, the
      language spoken and cultural norms. Such information is regarded as 'culturally
      sensitive'. However, an additional dimension is required. Information should be
      evaluated by the community and also specific users in order to determine its
      acceptability. This test of 'cultural competence' can ensure that such
      information has real practical value. An iterative evaluation process with
      feedback and refinement of information resources for minority ethnic groups is
      essential.

PMID- 19174571
TI  - Risk factors for death and the 3-year survival of patients with systemic
      sclerosis: the French ItinerAIR-Sclerodermie study.
AB  - OBJECTIVES: This longitudinal study investigated survival, risk factors and
      causes of death in the multicentre ItinerAIR-Sclerodermie cohort of patients with
      SSc without severe pulmonary fibrosis or severe left heart disease at baseline.
      METHODS: At 3-year follow-up, vital status was obtained from investigators or
      French national death records. Causes of death were classified as SSc-related or
      otherwise. Data were censored at 37 months, time of death or loss to follow-up,
      whichever was earlier. Survival was estimated using the Kaplan-Meier method.
      Multivariate survival analyses were conducted using the Cox model. RESULTS: In
      total, 546 patients were followed for a median duration of 37 months,
      representing 1547 patient-years. At baseline, the majority of patients were
      female, with lcSSc, mean age 54.9 +/- 13.0 years and mean duration of SSc of 8.8
      +/- 8.1 years. In total, 47 patients died, giving a 3-year survival of 91.1% and
      cumulative mortality of 3.04 deaths per 100 patient-years; 17 deaths (32.2%)
      resulted from pulmonary arterial hypertension (PAH) and eight (17.1%) from
      cancer. Of the 47 patients with PAH at baseline, 20 died during follow-up, giving
      a 3-year survival of 56.3%. In a multivariate analysis, PAH [hazard ratio (HR)
      7.246], age at first symptom (HR 1.052), duration of SSc (HR 1.047 per year) and
      Rodnan skin score (per one point) (HR 1.045) were associated with increased
      mortality. CONCLUSION: This 3-year study observed survival and mortality
      estimates that were comparable with previous reports. PAH increased the HR for
      mortality in patients with SSc, justifying yearly echocardiographic screening.

PMID- 19174575
TI  - BRCA1/2-associated and sporadic breast cancers: fellow travelers or not?

PMID- 19174576
TI  - The standard of perfection: thoughts about the laying hen model of ovarian
      cancer.

PMID- 19174577
TI  - Prevention of tumorigenesis in p53-null mammary epithelium by rexinoid
      bexarotene, tyrosine kinase inhibitor gefitinib, and celecoxib.
AB  - The chemopreventive effects of three agents, rexinoid bexarotene, tyrosine kinase
      inhibitor gefitinib, and celecoxib, were tested on mammary tumor development
      arising in p53-null mammary epithelium. The rexinoid bexarotene was the most
      efficacious inhibitor as it reduced mammary tumor development by 75% in virgin
      mice and significantly delayed mean tumor development by 98 days in hormone
      stimulated mice. The tyrosine kinase inhibitor gefitinib reduced mammary tumor
      incidence by 50% in virgin mice but did not significantly delay mean tumor
      latency in hormone-stimulated mice. Celecoxib did not reduce tumor incidence or
      mean tumor latency in either of the two models. The high doses of the rexinoid
      and the tyrosine kinase inhibitor did not affect the progression of tumors
      arising from the premalignant mammary outgrowth line, PN8a. A comparison of these
      agents with tamoxifen shows the superiority of tamoxifen in preventing tumor
      development in p53-null mammary cells. Similarly, a comparison of the results of
      the p53 model with other transgenic models in their response to the
      chemopreventive agents showed that mammary tumors arising from different
      oncogenic events will respond differently to the different agents.

PMID- 19174578
TI  - Mendelian randomization: how it can--and cannot--help confirm causal relations
      between nutrition and cancer.
AB  - Observational epidemiologic studies of nutrition and cancer have faced formidable
      methodologic obstacles, including dietary measurement error and confounding. We
      consider whether Mendelian randomization can help surmount these obstacles. The
      Mendelian randomization strategy, building on both the accuracy of genotyping and
      the random assortment of alleles at meiosis, involves searching for an
      association between a nutritional exposure-mimicking gene variant (a type of
      "instrumental variable") and cancer outcome. Necessary assumptions are that the
      gene is independent of cancer, given the exposure, and also independent of
      potential confounders. An allelic variant can serve as a proxy for diet and other
      nutritional factors through its effects on either metabolic processes or
      consumption behavior. Such a genetic proxy is measured with little error and
      usually is not confounded by nongenetic characteristics. Examples of potentially
      informative genes include LCT (lactase), ALDH2 (aldehyde dehydrogenase), and HFE
      (hemochromatosis), proxies, respectively, for dairy product intake, alcoholic
      beverage drinking, and serum iron levels. We show that use of these and other
      genes in Mendelian randomization studies of nutrition and cancer may be more
      complicated than previously recognized and discuss factors that can invalidate
      the instrumental variable assumptions or cloud the interpretation of these
      studies. Sample size requirements for Mendelian randomization studies of
      nutrition and cancer are shown to be potentially daunting; strong genetic proxies
      for exposure are necessary to make such studies feasible. We conclude that
      Mendelian randomization is not universally applicable, but, under the right
      conditions, can complement evidence for causal associations from conventional
      epidemiologic studies.

PMID- 19174581
TI  - High prevalence of preinvasive lesions adjacent to BRCA1/2-associated breast
      cancers.
AB  - Mutations in BRCA1 and BRCA2 increase a woman's lifetime risk of developing
      breast cancer by 43% to 84%. It was originally postulated that BRCA1/2-associated
      breast cancers develop more rapidly than sporadic cancers and may lack
      preinvasive lesions. More recent studies have found preinvasive lesions in
      prophylactic mastectomy specimens from mutation carriers; however, there is
      little information on the presence of preinvasive lesions in tissue adjacent to
      breast cancers. Our aim is to investigate the role of preinvasive lesions in BRCA
      associated breast carcinogenesis. We retrospectively compared BRCA1/2-associated
      breast cancers and sporadic breast cancers for the prevalence of preinvasive
      lesions [ductal carcinoma in situ (DCIS), lobular carcinoma in situ, and atypical
      lobular hyperplasia] in tissue adjacent to invasive breast cancers. Pathology was
      reviewed for 73 BRCA1/2-associated tumors from patients with breast cancer. We
      selected 146 patients with mutation-negative breast cancer as age-matched
      controls. Among the BRCA1/2-associated breast cancers, 59% had at least one
      associated preinvasive lesion compared with 75% of controls. Preinvasive lesions
      were more prevalent in BRCA2 mutation carriers than in BRCA1 mutation carriers
      (70% versus 52%, respectively). The most common preinvasive lesion in both groups
      was DCIS; 56% of BRCA1/2-associated breast cancers and 71% of the sporadic breast
      cancers had adjacent intraductal disease, respectively. Preinvasive lesions, most
      notably DCIS, are common in BRCA1/2-associated breast cancers. These findings
      suggest that BRCA1/2-associated breast cancers progress through the same
      intermediate steps as sporadic breast cancers, and that DCIS should be considered
      as a part of the BRCA1/2 tumor spectrum.

PMID- 19174580
TI  - Identification of modulated genes by three classes of chemopreventive agents at
      preneoplastic stages in a p53-null mouse mammary tumor model.
AB  - Genetically engineered mouse cancer models are among the most useful tools for
      testing the in vivo effectiveness of the various chemopreventive approaches. The
      p53-null mouse model of mammary carcinogenesis was previously characterized by us
      at the cellular, molecular, and pathologic levels. In a companion article, Medina
      et al. analyzed the efficacy of bexarotene, gefitinib, and celecoxib as
      chemopreventive agents in the same model. Here we report the global gene
      expression effects on mammary epithelium of such compounds, analyzing the data in
      light of their effectiveness as chemopreventive agents. SAGE was used to profile
      the transcriptome of p53-null mammary epithelium obtained from mice treated with
      each compound versus controls. This information was also compared with SAGE data
      from p53-null mouse mammary tumors. Gene expression changes induced by the
      chemopreventive treatments revealed a common core of 87 affected genes across
      treatments (P < 0.05). The effective compounds, bexarotene and gefitinib, may
      exert their chemopreventive activity, at least in part, by affecting a set of 34
      genes related to specific cellular pathways. The gene expression signature
      revealed various genes previously described to be associated with breast cancer,
      such as the activator protein-1 complex member Fos-like antigen 2 (Fosl2), early
      growth response 1 (Egr1), gelsolin (Gsn), and tumor protein translationally
      controlled 1 (Tpt1), among others. The concerted modulation of many of these
      transcripts before malignant transformation seems to be conducive to
      predominantly decrease cell proliferation. This study has revealed candidate key
      pathways that can be experimentally tested in the same model system and may
      constitute novel targets for future translational research.

PMID- 19174582
TI  - Screening for oral precancer with noninvasive genetic cytology.
AB  - Oral squamous cell carcinomas develop in precancerous fields consisting of
      genetically altered mucosal epithelial cells. These precancerous fields may
      appear as clinically visible lesions, in particular, oral leukoplakia, but the
      large majority remains clinically undetectable. The aim of this study was to
      assess the potential value of a noninvasive screening approach to detect
      precancerous fields. As a first step, we developed a suitable assay and
      investigated 25 leukoplakia patients and 20 noncancer control subjects.
      Exfoliated cells were removed by a brush from multiple small areas of the oral
      mucosa, including the leukoplakia. Brushed samples were investigated for allelic
      imbalance (AI) at chromosomes 3p, 9p, 11q, and 17p using microsatellite markers
      known to show frequent alterations in oral precancer. AI was absent in all (137)
      of the samples of the 20 control subjects, yielding a specificity of 100%. AI was
      detected in exfoliated cell samples of 40% (10 of 25) of the leukoplakia lesions
      studied. Genetic changes were also found outside the leukoplakia lesions. Most
      frequent was AI at 9p (9 of 10). The noninvasive assay was validated against the
      biopsy results of the leukoplakia lesions yielding an estimate of sensitivity of
      78% (7 of 9) and a positive predictive value of 100% (7 of 7). Altogether, these
      results show the feasibility of a noninvasive genetic screening approach for the
      detection and monitoring of oral precancer. This assay could therefore contribute
      to the secondary prevention of oral squamous cell carcinoma. The assay also shows
      promise for the detection of precancerous changes that are not macroscopically
      visible.

PMID- 19174583
TI  - Finasteride and high-grade prostate cancer.

PMID- 19174584
TI  - Ovarian adenocarcinomas in the laying hen and women share similar alterations in
      p53, ras, and HER-2/neu.
AB  - We examined alterations in the p53 tumor suppressor gene and the ras and HER
      2/neu oncogenes in chicken ovarian cancers to determine if these tumors have
      genetic alterations similar to those in human ovarian adenocarcinomas. Mutations
      in the p53 tumor suppressor gene and the H-ras and K-ras oncogenes were assessed
      by direct sequencing in 172 ovarian cancers obtained from 4-year-old birds
      enrolled at age 2 in two separate 2-year chemoprevention trials. Birds in trial B
      had approximately twice as many lifetime ovulations as those in trial A.
      Immunohistochemical staining for the HER-2/neu oncogene was done on a subset of
      avian ovarian and oviductal adenocarcinomas. Alterations in p53 were detected in
      48% of chicken ovarian cancers. Incidence of p53 alterations varied according to
      the number of lifetime ovulations, ranging from 14% in trial A to 96% in trial B
      (P < 0.01). No mutations were seen in H-ras, and only 2 of 172 (1.2%) tumors had
      K-ras mutations. Significant HER-2/neu staining was noted in 10 of 19 ovarian
      adenocarcinomas but in only 1 of 17 oviductal adenocarcinomas. Similar to human
      ovarian cancers, p53 alterations are common in chicken ovarian adenocarcinomas
      and correlate with the number of lifetime ovulations. Ras mutations are rare,
      similar to high-grade human ovarian cancers. HER-2/neu overexpression is common
      and may represent a marker to exclude an oviductal origin in cancers involving
      both the ovary and oviduct.

PMID- 19174585
TI  - A prospective, descriptive study to identify the microbiological profile of
      chronic wounds in outpatients.
AB  - Indiscriminate use of antibiotics for infected chronic wounds is a global problem
      that may contribute to delayed healing and the development of drug-resistant
      micro-organisms. A prospective, descriptive cohort study of 50 male and female
      outpatients (mean age 52.50 [+/- 14.84] years, range 18-90) with 52 chronic
      wounds was conducted to investigate the microbiological profile and prevalence of
      drug-resistant strains in chronic nonhealing wounds to develop an evidence-based
      approach to antibiotic therapy until drug sensitivity reports are available. Mean
      wound duration was 8.23 (+/- 12.35) months (range 1.5-72), average wound size was
      29.70 (+/- 37.83) cm, and most patients had a lower extremity wound and diabetes
      mellitus (n = 20). Pus and tissue samples were cultured and tested. Most (45)
      wounds contained a single organism and nine different genera were isolated. Of
      those, 39 were Gram-negative and 11 were Gram-positive (z = 5.50, P = <0.001).
      The most common organisms were Pseudomonas (21 wounds) and Escherichia coli
      (eight wounds). Pseudomonas aeruginosa was more common in patients with diabetes
      mellitus, in lower extremity ulcers, and in ulcers >20 cm2 (z-test, P <0.05). The
      presence of two organisms was more commonly observed in postsurgical/traumatic
      wounds. Ten (10) out of 55 pathogens (18.18%) isolated were drug-resistant,
      including Pseudomonas (seven), methicillin-resistant Staphylococcus aureus (one),
      and extended-spectrum beta lactamase (two--E. coli and Citrobacter). Most (70%)
      drug-resistant pathogens were obtained from persons with diabetes mellitus.
      Overall sensitivity to piperacillin and tazobactum combination was high. Because
      the prevalence of monomicrobial flora in chronic wounds is high, if a wound
      infection is suspected, empiric therapy should target the most prevalent flora.
      The high rate of drug-resistant Pseudomonas and MRSA strains should discourage
      antibiotic use in chronic ulcers before obtaining culture results.

PMID- 19174586
TI  - The impact of noncontact, nonthermal, low-frequency ultrasound on bacterial
      counts in experimental and chronic wounds.
AB  - Preventing wound infection and the development of resistant bacteria are
      important concerns in wound management. To determine if noncontact, nonthermal,
      low-frequency ultrasound therapy is effective in controlling wound bacterial
      colony counts, a series of four related experiments was conducted. First,
      ultrasound penetration in both wounded and intact skin was assessed in vitro.
      Compared to sham, noncontact ultrasound penetrated farther into both wounded (3
      mm to 3.5 mm versus 0.35 mm to 0.50 mm) and intact (2.0 mm to 2.5 mm versus 0.05
      mm to 0.07 mm, respectively) pig skin. Second, using an in vitro model to stain
      and count live/dead bacteria, 0% of sham treated and 33% of Pseudomonas
      aeruginosa, 40% of Escherichia coli and 27% of Enterococcus faecalis were dead
      after one ultrasound application. Minimal effects on methicillin-resistant
      Staphylococcus aureus and S. aureus were observed. Third, using an in vivo model,
      after 1 week, while differences between different bacterial species were
      observed, overall bacterial quantity decreased with ultrasound treatment (from
      7.2 +/- 0.79 to 6.7 +/- 0.91 colony forming units per gram of tissue [CFU/g]) and
      silver antimicrobial dressings (from 7.2 +/- 0.79 to 5.7 +/- 0.6 CFU/g) but
      increased to 8.6 +/- 0.15 CFU/g for sham and 8.6 +/- 0.06 CFU/g for water
      moistened gauze. Fourth, 11 patients (average age 60 years) with pressure ulcers
      containing bacterial counts >10(5) CFU/g of tissue received 2 weeks of noncontact
      ultrasound therapy. The quantities of seven bacterial organisms were reduced
      substantially from baseline to 2 weeks post treatment. None of the wounds
      exhibited signs of a clinical infection during the treatment period and no
      adverse events were observed. Taken together, these four studies indicate that
      noncontact ultrasound can be used to reduce bacterial quantity. Controlled
      clinical studies are warranted to ascertain the efficacy of this treatment and to
      further elucidate its effects on various Gram-negative and Gram-positive
      bacteria.

PMID- 19174587
TI  - A retrospective cohort study of factors that affect healing in long-term care
      residents with chronic wounds.
AB  - Chronic ulcers such as pressure, ischemic, and venous ulcers are common in long
      term care (LTC) and frequently do not heal. A retrospective medical records
      review of all LTC residents referred to a wound consultative service between
      April 1999 and January 2007 was conducted to assess predictors of 6-month healing
      outcome. Variables abstracted and analyzed included wound, resident demographic,
      and laboratory values at diagnosis and comorbid medical illnesses. The average
      age of study participants (n = 397) was 78.1 years (+/- 11), 47% were men, 48%
      had more than one wound, and the most common wound diagnosis was pressure ulcer
      (n = 163). After 6 months, 66% of ulcers were not healed. The odds ratio for
      nonhealing was significantly higher in residents who had more wounds, a larger
      wound area, diabetes mellitus, or peripheral vascular disease and lower in
      residents with increased age and hemoglobin values and/or a history of stroke,
      depression, dementia, degenerative arthritis, peripheral neuropathy, and falls.
      After adjustment in the multivariate model, only the number of wounds and
      hemoglobin level remained significant predictors of healing status. A higher
      number of chronic ulcers and lower hemoglobin counts increased the risk of
      nonhealing after 6 months of care. Including these variables in LTC resident
      assessments may help clinicians ascertain expected outcomes of care.

PMID- 19174588
TI  - Using leptospermum honey to manage wounds impaired by radiotherapy: a case
      series.
AB  - Radiation-induced tissue injury and wounds with radiation-impaired healing are
      traumatic for patients and challenging for their caregivers. Standardized
      management approaches do not exist. The effect of Leptospermum honey as a primary
      dressing for managing these wounds was assessed in four patients (age range 63 to
      93 years) who had previously undergone radiotherapy that left them with fragile
      friable areas of damaged skin that did not respond to conventional treatment.
      Compromised areas involved the neck, cheek, groin/perineum, and chest. In
      patients 1 and 2, after topical application of honey via hydrofiber rope and
      nonadhesive foam, respectively, improvements in the size and condition of
      wound/periwound area and a reduction in pain were noted before death or loss to
      follow-up. After including honey in the treatment regimen of patients 3 and 4,
      complete healing was noted in 2.5 weeks (with honey and paraffin) and 6 weeks
      (with honey-soaked hydrofiber rope), respectively. No adverse events were
      reported. Honey as an adjunct to conventional wound/skin care post radiation
      therapy shows promise for less painful healing in these chronic wounds.
      Prospective, randomized, controlled clinical studies are needed to confirm these
      observations.

PMID- 19174589
TI  - Effect of potential of ion optic system and gas-filled octapole collision cell on
      mass discrimination in lead isotopic measurements ((206)Pb/(207)Pb,
      (208)Pb/(207)Pb and (206)Pb/2(208)Pb) by quadrupole-based inductively-coupled
      plasma mass spectrometry.
AB  - The accuracy and precision of lead isotope ratio measurements by quadrupole-based
      inductively-coupled plalsma-mass spectrometry (ICP-MS) can be limited by any of a
      number of instrumental factors being mass bias one of the most relevant. Mass
      bias can be defined as the deviation of measured isotope ratios from the "true
      value" due to the different transmission of ions according to their masses before
      the final detection. In the present research, a systematic study aimed at
      obtaining a more profound insight into to what extent the potential of the ion
      optic system and gas-filled octapole collision cell influence the mass
      discrimination in lead isotopic measurements ((206)Pb/(207)Pb, (208)Pb/(207)Pb
      and (206)Pb/(208)Pb) using ICP-QMS instrumentation was carried out. From the
      results obtained, it could be concluded that, in most cases, the effect of ion
      lens potential variation in mass discrimination is not really significant when
      working in maximum ion intensity regions. On the other hand, the application of
      pressurized conditions in the octapole collision/reaction cell using He and H(2)
      as target gases does not lead to an improvement in ion sensitivity but, instead,
      introduces a significant mass bias effect, particularly when using high He flow
      rates (6-8 mL min(-1)). In this latter case, the use of Tl as the internal
      standard ((203)Tl/(205)Tl) proved to be suitable to correct the mass bias drift
      and the calculated mass discrimination percentage values decreased from 3.61% to
      0.33%. The use of the gas-filled octapole collision cell does not lead to an
      improvement in lead isotope ratio precision compared to vented conditions.

PMID- 19174590
TI  - Gas-phase intramolecular elimination reaction studies of steviol glycosides in
      positive electrospray and tandem mass spectrometry.
AB  - This paper reports the first study of the gas-phase intramolecular elimination
      reaction of steviol glycosides in positive electrospray mass spectrometry. The
      observed glycosylated product ions are proposed to be formed via an
      intramolecular elimination of sugar units from the parent molecule ion. It was
      further proven by MS/MS studies and deuterium labeling experiments with one of
      the steviol glycosides, rebaudioside A. These mass spectrometric results
      confirmed that the new glycosylated product ions observed are most likely formed
      by the combination of glucose moieties (Glu) II-IV and Glu I via a gas-phase
      intramolecular elimination reaction.

PMID- 19174591
TI  - Pyrolysis of waste polypropylene and characterisation of tar.
AB  - Waste polypropylene (PP) has been pyrolysed to obtain mainly a liquid tar product
      of high yield (83.5%) with the balance as gas (15.5%) and a little residue
      (1.0%). The elemental composition of the PP tar was: C: 87.1%, H: 12.6% and
      O+others: 0.4% (by difference). The tar samples have been characterised by gas
      chromatography/mass spectrometry, heated-probe mass spectrometry and laser 
      desorption mass spectrometry (LD- MS), to give molecular mass distributions for
      comparison with molecular mass ranges indicated by size-exclusion chromatography
      (SEC). About 50% of the tar was soluble in 1-methyl-2-pyrrolidinone, the solvent
      used for SEC. It appeared to consist mostly of low molecular mass materials with
      elution time at 20-27 min. Mass ranges from SEC and LD-MS agreed approximately in
      showing the upper mass limit of the tar to be about 1200 u, consisting of
      aromatics, alkenes, dialkenes and only minor quantities of alkanes.

PMID- 19174592
TI  - Exploration of mononucleotides as fixed ligands towards chiral discrimination of
      hexose monosaccharides by the kinetic method.
AB  - The most recent version of the kinetic method, i.e. fixed ligand method, is
      applied towards chiral discrimination of three pairs of enantiomeric hexose
      monosaccharides under mass spectral conditions. Naturally occurring
      mononucleotides are used as fixed ligands (FL) and the amino acids are selected
      as the chiral references (ref) to discriminate the analyte (A), the enantiomers
      of glucose, mannose and galactose. Chiral discrimination is achieved by
      investigating the collision-induced dissociation spectra of trimeric complex ion,
      [Ni(II)(FL)(ref)(A)-H](+) generated by electrospraying the solution mixture of D-
      or L- analyte (A), FL, amino acid (ref) and NiCl(2). The relative abundance of
      product ions resulting from the competitive loss of reference amino acid and
      analyte are considered for measuring the degree of chiral discrimination by
      applying the kinetic method. L-Asp, L-Thr, L-Glu, L-Trp and L-Ser are found as
      suitable reference compounds. Among the tested mononucleotides (5'AMP, 5'GMP,
      5'CMP, 5'UMP and 5'TMP), 5'GMP is found to be the best for the studied analytes.
      Chiral discrimination is found to depend on the nature of the monosaccharide, the
      functional groups present in the side chain of reference amino acids and the
      configuration of reference amino acids.

PMID- 19174593
TI  - Fragmentation of a non-ester pyrethroid insecticide by atmospheric pressure
      chemical ionization.
AB  - We elucidated the mechanism of fragmentation of ethophenprox (Mw = 376), a non
      ester pyrethroid insecticide, in the presence of a proton, by using tandem mass
      spectrometry in combination with an atmospheric pressure chemical ionization
      technique in positive-ion mode. When methanol or acetonitrile was used as a
      solvent, no protonated ethophenprox ion was observed in the mass spectra even at
      low cone voltage (10 V), at which solvent cluster ions can exist. Instead of the
      protonated ion, an unexpected m/z 359 ion was strongly observed under all
      conditions examined. The product ion spectrum of the m/z 359 ion obtained under
      low collision energy (20 eV) showed that this ion can be formed through
      structural rearrangement involving water loss mainly via the six-centered pathway
      in this system, although two pathways (five-centered and six-centered) to form
      the m/z 359 ion are suggested in the literature.

PMID- 19174594
TI  - Determination of 20(S)-ginsenoside Rh1 and its aglycone 20(S)-protopanaxatriol in
      rat plasma by sensitive LC-APCI-MS method and its application to pharmacokinetic
      study.
AB  - Liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry
      (LC-APCI-MS) method has been developed for the measurement of the concentrations
      of 20(S)-ginsenoside Rh1 and its aglycone 20(S)-protopanaxatriol in rat plasma
      with panaxatriol as internal standard. The method involved single liquid-liquid
      extraction of both 20(S)-ginsenoside Rh1 and 20(S)-protopanaxatriol from plasma
      samples with n-butanol. The limit of quantification (LOQ) was 5 ng mL(-1) for
      both compounds. The method was validated within the linear range 5-2000 ng.mL(-1)
      for both compounds. The correlation coefficient for the calibration regression
      line was 0.999 or better. Intra-day and inter-day accuracy were better than 15%.
      The method has been successfully used for the pharmacokinetic studies in rats.
      After intravenous administrations, the mean retention times of 20(S)-ginsenoside
      Rh1 and 20(S)-protopanaxatriol were 17.1 +/- 2.0 min and 3.46 +/- 0.33 h,
      respectively.

PMID- 19174595
TI  - Determination of a binding site of Cu and Ni metal ions with oxytocin peptide by
      electrospray tandem mass spectrometry and multiple mass spectrometry.
AB  - The structures of a [Ni(II), Cu(II)- - -oxytocin] complex were investigated by
      electrospray ionization-mass spectrometry in positive mode. The fragmentation
      patterns of the [Ni(II), Cu(II) + OT](2+) complex were analyzed by tandem mass
      spectrometry and multiple mass spectrometry in the gas-phase. Conformations of
      metalII ion binding to oxytocin (OT) have been studied to explain the biological
      activity difference in the physiological solution. The [Ni(II) + OT](2+) and
      [Cu(II) + OT](2+) complexes were observed as the main ions in MS spectra. The
      Cys1-Tyr2-Ile3-Gln4 sequence of oxytocin is suggested to be a binding site for
      the [Ni(II) + OT](2+) gas-phase complex and Ile3-Gln4-Asn5-Cys6 sequence for the
      [Cu(II) + OT](2+) gas-phase complex. The specific binding site of CuII ion in the
      [Cu(II) + OT](2+) complex is explained as a reason of the negligible effect on
      the [Cu(II)- - -oxytocin] biological activity in aqueous solution.

PMID- 19174596
TI  - Improved mammographic CAD performance using multi-view information: a Bayesian
      network framework.
AB  - Mammographic reading by radiologists requires the comparison of at least two
      breast projections (views) for the detection and the diagnosis of breast
      abnormalities. Despite their reported potential to support radiologists, most
      mammographic computer-aided detection (CAD) systems have a major limitation: as
      opposed to the radiologist's practice, computerized systems analyze each view
      independently. To tackle this problem, in this paper, we propose a Bayesian
      network framework for multi-view mammographic analysis, with main focus on breast
      cancer detection at a patient level. We use causal-independence models and
      context modeling over the whole breast represented as links between the regions
      detected by a single-view CAD system in the two breast projections. The proposed
      approach is implemented and tested with screening mammograms for 1063 cases of
      whom 385 had breast cancer. The single-view CAD system is used as a benchmark
      method for comparison. The results show that our multi-view modeling leads to
      significantly better performance in discriminating between normal and cancerous
      patients. We also demonstrate the potential of our multi-view system for
      selecting the most suspicious cases.

PMID- 19174597
TI  - Evaluation of w values for carbon beams in air, using a graphite calorimeter.
AB  - Despite recent progress in carbon therapy, accurate values for physical data such
      as the w value in air or stopping power ratios for ionization chamber dosimetry
      have not been obtained. The absorbed dose to graphite obtained with the graphite
      calorimeter was compared with that obtained using the ionization chambers
      following the IAEA protocol in order to evaluate the w values in air for mono
      energetic carbon beams of 135, 290, 400 and 430 MeV/n. Two cylindrical chambers
      (PTW type 30001 and PTW type 30011, Farmer) and two plane-parallel chambers (PTW
      type 23343, Markus and PTW type 34001, Roos) calibrated by the absorbed dose to
      graphite and exposure to the (60)Co photon beam were used. The comparisons to our
      calorimeter measurements revealed that, using the ionization chambers, the
      absorbed dose to graphite comes out low by 2-6% in this experimental energy range
      and with these chamber types and calibration methods. In the therapeutic energy
      range, the w values in air for carbon beams indicated a slight energy dependence;
      we, however, assumed these values to be constant for practical use because of the
      large uncertainty and unknown perturbation factors of the ionization chambers.
      The w values in air of the carbon beams were evaluated to be 35.72 J C(-1) +/-
      1.5% in the energy range used in this study. This value is 3.5% larger than that
      recommended by the IAEA TRS 398 for heavy-ion beams. Using this evaluated result,
      the absorbed dose to water in the carbon beams would be increased by the same
      amount.

PMID- 19174598
TI  - Analysis of carotid lumen surface morphology using three-dimensional ultrasound
      imaging.
AB  - Carotid plaque surface irregularity and ulcerations play an important role in the
      risk of ischemic stroke. Ulcerated or fissured plaque, characterized by irregular
      surface morphology, exposes thrombogenic materials to the bloodstream, possibly
      leading to life- or brain-threatening thrombosis and embolization. Therefore, the
      quantification of plaque surface irregularity is important to identify high-risk
      plaques that would likely lead to vascular events. Although a number of studies
      have characterized plaque surface irregularity using subjective classification
      schemes with two or more categories, only a few have quantified surface
      irregularity using an objective and continuous quantity, such as Gaussian or mean
      curvature. In this work, our goal was to use both Gaussian and mean curvatures
      for identifying ulcers from 3D carotid ultrasound (US) images of human subjects.
      Before performing experiments using patient data, we verified the numerical
      accuracy of the surface curvature computation method using discrete spheres and
      tori with different sampling intervals. We also showed that three ulcers of the
      vascular phantom with 2 mm, 3 mm and 4 mm diameters were associated with high
      Gaussian and mean curvatures, and thus, were easily detected. Finally, we
      demonstrated the application of the proposed method for detecting ulcers on
      luminal surfaces, which were segmented from the 3D US images acquired for two
      human subjects.

PMID- 19174599
TI  - pH-induced contrast in viscoelasticity imaging of biopolymers.
AB  - Understanding contrast mechanisms and identifying discriminating features is at
      the heart of diagnostic imaging development. This paper focuses on how pH
      influences the viscoelastic properties of biopolymers to better understand the
      effects of extracellular pH on breast tumour elasticity imaging. Extracellular pH
      is known to decrease as much as 1 pH unit in breast tumours, thus creating a
      dangerous environment that increases cellular mutation rates and therapeutic
      resistance. We used a gelatin hydrogel phantom to isolate the effects of pH on a
      polymer network with similarities to the extracellular matrix in breast stroma.
      Using compressive unconfined creep and stress relaxation measurements, we
      systematically measured the viscoelastic features sensitive to pH by way of time
      domain models and complex modulus analysis. These results are used to determine
      the sensitivity of quasi-static ultrasonic elasticity imaging to pH. We found a
      strong elastic response of the polymer network to pH, such that the matrix
      stiffness decreases as pH was reduced; however, the viscous response of the
      medium to pH was negligible. While physiological features of breast stroma such
      as proteoglycans and vascular networks are not included in our hydrogel model,
      observations in this study provide insight into viscoelastic features specific to
      pH changes in the collagenous stromal network. These observations suggest that
      the large contrast common in breast tumours with desmoplasia may be reduced under
      acidic conditions, and that viscoelastic features are unlikely to improve
      discriminability.

PMID- 19174600
TI  - Quality of life and psychological problems of patients with oral mucosal disease
      in dermatological practice.
AB  - BACKGROUND: Dermatologists see patients with oral mucosal conditions. OBJECTIVES:
      To evaluate oral health-related quality of life (OHRQoL) and the burden of
      disease of dermatological patients with oral mucosal diseases. METHODS: All
      consecutive patients (April 2005 to November 2006) coming to the oral health care
      unit of the IDI-IRCCS in Rome were asked to complete oral health-specific (14
      item Oral Health Impact Profile, OHIP-14), generic health status (12-item Short
      Form of Medical Outcome Study, SF-12) and general psychological (12-item General
      Health Questionnaire, GHQ-12) questionnaires. Physicians and patients gave a
      global assessment of severity of disease on a 5-point scale. RESULTS: 206
      patients participated. Recurrent aphthous stomatitis (RAS) had the highest impact
      on OHRQoL. Women had poorer OHRQoL both on physical and mental scales of the SF
      12. 33.7% of patients were GHQ-positive with women showing a much higher
      prevalence than men (39.7 vs. 20.3%). OHIP-14 high scores were observed in RAS,
      followed by oral lichen planus and burning mouth syndrome. Patients whose
      condition was 'underestimated' by the physicians had the worst OHRQoL and
      psychological status. CONCLUSIONS: Administration of specific and generic
      questionnaires provides a detailed picture of the impact of oral diseases on
      patients, which adds information that may be useful in clinical practice. The
      possible contribution of such tools should be assessed in a randomized controlled
      trial.

PMID- 19174601
TI  - Safety of diagnostic bronchoscopy in patients with pulmonary hypertension.
AB  - BACKGROUND: Patients with pulmonary hypertension (PH) are considered to be at
      risk for complications associated with flexible bronchoscopy (FB). Although
      previous reports suggest that transbronchial biopsies increase the risk for
      hemorrhage in this population, data are limited to survey analyses and isolated
      reports. OBJECTIVES: It was the aim of this study to describe our experience with
      FB and to determine if bronchoscopic procedures are associated with adverse
      events in this population. METHODS: We conducted a retrospective review of
      patients with diagnosis of PH who underwent FB at the Cleveland Clinic between
      2002 and 2005. Patients without PH who underwent FB by the same pulmonary
      physician were used as controls. RESULTS: A total of 90 patients, PH (n = 45)
      versus controls (n = 45), were included. The mean systolic pulmonary artery
      pressure in patients with PH was 58 +/- 7 mm Hg. Patients with PH had higher
      oxygen requirements at baseline (FiO(2) 0.42 vs. 0.3%; p = 0.01). The total
      number of procedures was similar between the groups (95 vs. 102). Procedures
      performed were bronchoalveolar lavage (21 vs. 13), transbronchial biopsies (24
      vs. 32) and transbronchial needle aspiration (7 vs. 6). There were no hemodynamic
      complications or episodes of respiratory failure associated with the procedures.
      None of the patients had significant hemorrhage and only 2 developed mild
      bleeding which resolved spontaneously. Similarly, none required hospitalization
      or transfer to an intensive care unit. CONCLUSIONS: FB can be performed safely in
      patients with mild to moderate PH. Transbronchial biopsies are not associated
      with worsening hypoxemia or an increased risk of hemorrhage. Prospective studies
      with hemodynamic measurements are necessary to confirm these findings.

PMID- 19174602
TI  - Measuring FEV(6) for detecting early airway obstruction in the primary care
      setting. Quality and utility of the new PiKo-6 device.
AB  - BACKGROUND: The prevalence of asthma and chronic obstructive pulmonary disease
      (COPD) is high ( approximately 7.4-18%) in the general population, but less than
      half are diagnosed. Several studies have shown FEV(6) as a good surrogate marker
      for forced vital capacity (FVC) to detect airflow limitations. OBJECTIVES: The
      aim of this study was to evaluate if it is possible to simplify and improve the
      diagnosis of so far undiagnosed asthma or COPD in the primary care setting by
      measuring FEV(6) with a new simple screening device (PiKo-6). METHODS: 507
      patients were recruited from three general practices from May to June 2005.
      Patients with any known pulmonary disease were excluded by questionnaire. FEV(1),
      FEV(6) and FEV(1)/FEV(6) were determined using a PiKo-6 device. Patients with an
      FEV(1)/FEV(6) <80% (PiKo positive) were invited to a standardized pulmonary
      function test to confirm or rule out airflow limitation. RESULTS: 401 (79.1%)
      patients showed FEV(1)/FEV(6) > or =80% (PiKo negative), and 106 (20.9%) patients
      were PiKo positive. Of the 106 PiKo-positive patients, 74 patients (14.7% of
      total) agreed to further studies and 18 patients (3.6%) of them suffered from
      COPD [COPD 0: 5 (1.0%); COPD I: 9 (1.8%); COPD II: 4 (0.8%), and none with COPD
      III or IV] and 14 patients (2.8%) suffered from bronchial hyperresponsiveness or
      asthma. In 42 patients (8.3%), the pulmonary function test was normal.
      CONCLUSIONS: Measurement of FEV(6) using a new simple screening device (PiKo-6)
      may improve the detection rate of undiagnosed airflow limitation in the primary
      care setting. However, patients should be carefully selected.

PMID- 19174603
TI  - Repigmentation by outer-root-sheath-derived melanocytes: proof of concept in
      vitiligo and leucoderma.
AB  - BACKGROUND: Treatment of depigmented skin is an unmet medical need. OBJECTIVE:
      Melanocytes or stem cells thereof residing in the outer root sheath (ORS) of hair
      follicles might be used to repigment skin. METHODS: After de-epidermisation,
      autologous ORS cell solutions were applied to 5 patients with vitiligo and 1 with
      leucoderma. RESULTS: Stable repigmentation in a variable percentage was
      documented in all the patients. CONCLUSION: Applying ORS-derived melanocytes is a
      promising technology to improve autologous melanocyte transplantation.

PMID- 19174604
TI  - Central neural regulation of cardiovascular function by angiotensin: a focus on
      the rostral ventrolateral medulla.
AB  - Angiotensin II acts through specific receptors to alter several brain functions
      including fluid and electrolyte control, neuroendocrine function and autonomic
      efferent activity. This review discusses one brain site, the rostral
      ventrolateral medulla, where the actions of angiotensin II have been intensively
      studied. The rostral ventrolateral medulla plays a critical role in the
      generation and regulation of sympathetic activity to the cardiovascular system
      and hence is important for blood pressure control. Current evidence indicates
      that angiotensin II activates neurons in the rostral ventrolateral medulla via
      the AT(1A) receptor. In some models of cardiovascular disease, blockade of AT(1)
      receptors in the rostral ventrolateral medulla reduces sympathetic nerve activity
      and blood pressure suggesting that overactivity of the angiotensin system in this
      nucleus may play a role in the maintenance of high blood pressure.

PMID- 19174605
TI  - Survival and prognostic factor analysis of 146 metastatic neuroendocrine tumors
      of the mid-gut.
AB  - BACKGROUND: Gastrointestinal neuroendocrine tumors (NETs) are heterogeneous
      neoplasms that vary in mortality according to location of primary tumor and stage
      of disease. Past analyses of survival suggest a trend towards improving longevity
      among patients with metastatic mid-gut NETs. METHODS: We evaluated all cases of
      metastatic NETs of the mid-gut seen in our institution between 1999 and 2003,
      measuring survival from time of diagnosis of distant metastatic disease. Median
      and 5-year survival rates were estimated using Kaplan-Meier methodology. We
      assessed the impact of various prognostic factors including age, gender, hepatic
      cytoreductive surgery, and operative resection of the primary tumor. RESULTS: 146
      cases of metastatic mid-gut NETs were identified. The median overall survival was
      103 months and the 5-year survival rate was 75%. Most patients (91%) received
      octreotide therapy. Other medical treatments included hepatic artery
      embolization, chemotherapy, and peptide receptor radiotherapy. Primary tumor
      resection was performed in 69% of cases, and hepatic cytoreductive surgery in 22%
      of cases. A median survival of 95 months was observed among patients who did not
      undergo cytoreductive surgery. Operative resection of the primary tumor was not
      associated with a significant survival advantage. CONCLUSIONS: Median overall
      survival is 103 months (8.5 years) in patients with metastatic mid-gut NETs.
      Among patients who are not candidates for hepatic cytoreductive surgery, median
      survival is 95 months (7.9 years). Resection of the primary tumor does not appear
      to be associated with a survival benefit in the metastatic setting.

PMID- 19174606
TI  - Methylation of p16INK4A and mitotic arrest defective protein 2 (MAD2) genes in
      gastric marginal-zone B-cell lymphomas.
AB  - BACKGROUND: Products of cyclin-dependent kinase inhibitor p16(INK4A)and mitotic
      arrest defective protein 2 (MAD2) genesare key regulator proteins at the G1
      restriction point and mitotic checkpoint of the cell cycle. The objective of this
      study was to investigate the role of promoter methylation of p16(INK4A) and MAD2
      genes in gastric marginal-zone B-cell lymphoma (MZBCL). MATERIALS AND METHODS:
      Gastric biopsies from 40 patients were analyzed by methylation-specific
      polymerase chain reaction, and the methylation status was compared with the
      results of BCL10 expression and t(11;18)(q21;q21) translocation. RESULTS AND
      CONCLUSION: p16(INK4A) was methylated in 30 of 40 MZBCLs (75%). The lymphomas
      with p16(INK4A) methylation tended to be negative for t(11;18)(q21;q21) (p =
      0.011). MAD2 gene was methylated in 23 of 38 MZBCLs (61%). Lymphomas with MAD2
      gene methylation more frequently expressed BCL10 (p = 0.037). These methylation
      profiles suggest that p16(INK4A) and MAD2 gene may play a role in the
      pathogenesis of MZBCL via different pathways; MAD2 gene is Helicobacter pylori
      independent with a close association with BCL10 while p16(INK4A) is H. pylori
      dependent with an inverse correlation with the t(11;18)(q21;q21) translocation.

PMID- 19174607
TI  - In vitro evaluation of dentifrice with low fluoride content supplemented with
      trimetaphosphate.
AB  - One way to reduce dental fluorosis is by reducing the fluoride (F) concentration
      in dentifrice, but low-F dentifrice should be as effective as a standard
      dentifrice. This study evaluated in vitro whether the supplementation with sodium
      trimetaphosphate (TMP) of a dentifrice with low F content (500 microg/g) would
      provide a similar effect to that of a standard dentifrice. Bovine enamel blocks
      were submitted to a pH cycling regime incorporating daily exposures to a slurry
      of dentifrice: a low-F dentifrice with or without 0.1-3.0% TMP; an F-free,
      phosphate-free dentifrice (negative control), or a dentifrice with 1,100 microg/g
      F (positive control). The addition of TMP to dentifrice with or without F was
      associated with higher surface hardness and decreased loss of integrated
      subsurface hardness after pH cycling. The combination of 1% TMP and 500 microg
      F/g had a greater effect than the positive control dentifrice. It is concluded
      that the addition of TMP to the 500-microg F/g dentifrice allowed a similar or
      larger effect as compared with a standard dentifrice in this in vitro model.

PMID- 19174608
TI  - Hyperbaric oxygen reduces inflammatory response in acute pancreatitis by
      inhibiting NF-kappaB activation.
AB  - AIM: The mechanism of hyperbaric oxygen (HBO) therapy for acute pancreatitis has
      not been fully clarified yet. The main purpose of this study was to investigate
      the effect of HBO on nuclear factor kappaB (NF-kappaB) activation and the
      inflammatory response in rats with acute necrotizing pancreatitis (ANP). METHODS:
      A total of 120 male Sprague-Dawley rats were randomly divided into 3 groups (40
      in each): control, ANP and ANP + HBO. ANP rat models were established by a
      retrograde injection of 5% sodium taurocholate into the pancreatic duct. HBO
      treatment was performed at 2.5-fold absolute atmospheric pressure in 90% oxygen
      for 1, 3, 5, and 7 h. The activation of NF-kappaB and its inhibitor IkappaBalpha
      in peripheral blood neutrophilic granulocytes was measured by electrophoretic
      mobility shift assay and Western blot, respectively. The inflammatory cytokines
      [interleukin (IL)-2, IL-6, tumor necrosis factor-alpha (TNF-alpha), and
      intercellular adhesion molecule 1] in the blood were measured by enzyme-linked
      immunosorbent assay. RESULTS: The blood levels of inflammatory cytokines and NF
      kappaB activation were significantly increased in ANP rats compared to control
      rats, but IkappaBalpha activation was suppressed. The levels of the elevated
      inflammatory cytokines were positively correlated with the changes in NF-kappaB
      activation. After HBO treatment, the blood levels of inflammatory cytokines and
      NF-kappaB activation were significantly decreased in the ANP + HBO group in a
      time-dependent manner, but IkappaBalpha activation was increased. CONCLUSION: Our
      findings suggest that acute pancreatitis is associated with the upregulation of
      cytokines in blood as well as upregulation of NF-kappaB levels and downregulation
      of IkappaBalpha activation in peripheral blood neutrophilic granulocytes. In
      contrast, HBO plays a role in acute pancreatitis treatment by normalizing these
      changes.

PMID- 19174609
TI  - Retrospective analysis of thyroid nodules by clinical and pathological
      characteristics, and ultrasonographically detected calcification correlated to
      thyroid carcinoma in South China.
AB  - OBJECTIVE: To investigate the clinical and pathological characteristics of
      thyroid nodules, as well as to evaluate the significance of ultrasonographically
      detected thyroid calcification in the diagnosis of thyroid carcinomas. METHODS:
      Retrospective data were studied from 1,051 consecutive patients who underwent a
      thyroidectomy in the Provincial Hospital of Fujian Medical University in South
      China between January 2003 and July 2006 for nodular thyroid disease. Complete
      sonographical information before surgery was only collected from 758 of the 1,051
      patients. RESULTS: Among the 1,051 patients, benign lesions were found in 857
      (81.54%) patients, of whom 612 (71.41%) were nodular goiter; malignant lesions
      were found in 194 (18.46%) patients, in whom benign thyroid lesions were also
      found in 85 (43.81%) patients. A total of 48 patients suffered from
      microcarcinomas, of whom 37 patients had benign lesions; these 37 accounted for
      43.53 and 77.08%, respectively, of the 85 malignant cases with benign lesions and
      the 48 cases with microcarcinomas. In the 758 patients who underwent thyroid
      ultrasonography before surgery, intrathyroidal calcifications were apparent in
      243 patients (32.06%). The incidence of calcification was significantly higher in
      patients with thyroid carcinoma (54.17%) than in those with benign lesions
      (26.87%; p < 0.005). Detection of calcification in thyroid lesions by ultrasound
      had a sensitivity of 32.38% and a specificity of 87.35%, with an OR of 3.31 (95%
      CI, 2.24-4.63), positive likelihood ratio of 2.56, negative likelihood ratio of
      0.77 and a kappa value of 0.23. CONCLUSION: Thyroid carcinoma, especially
      microcarcinoma, often coexists with benign thyroid disease. Calcification
      detected by thyroid ultrasound represents a risk factor for malignancy, but is of
      limited use as a sole marker of malignancy.

PMID- 19174610
TI  - Lower extremity neuromotor function and short-term ambulatory potential following
      in utero myelomeningocele surgery.
AB  - OBJECTIVE: To evaluate lower extremity neuromotor function (LENF) and short-term
      ambulatory potential following fetal myelomeningocele (fMMC) closure. METHODS:
      Retrospective chart review of 54 children that underwent fMMC closure at our
      institution prior to the NIHCD-MOMS trial. Neonatal LENF was compared to
      predicted function based on spinal lesion level assigned by prenatal ultrasound.
      Ambulatory status was classified as independent walkers (walks without assistive
      appliances), assisted walker (requires walking aid), and non-ambulatory
      (wheelchair bound). RESULTS: Thoracic, lumbar, and sacral level lesions were
      present in 4, 44 and 6 fMMC infants, respectively. 31/54 of fMMC children (57.4%;
      median: 2 levels, range: 1-5) had better than predicted, 13/54 (24.1%) same as
      predicted and 10/54 (18.5%; median: 1 level, range: 1-2) worse than predicted
      LENF at birth. At a median follow-up age of 66 months (36-113), 37/54 (69%) walk
      independently, 13/54 (24%) are assisted walkers, and 4/54 (7%) are wheelchair
      dependent. The strongest factors predicting a lower likelihood to walk
      independently were higher-level lesion (>L4, p = 0.001) and the development of
      clubfoot deformity after fetal intervention (p = 0.026). Despite the observed
      improved ambulatory status, structured evaluation of coordinative skills revealed
      that the majority of independent ambulators and all children that require
      assistive devices to walk experience significant deficits in lower extremity
      coordination. CONCLUSIONS: We observed that fMMC surgery in this highly selective
      population results in better than predicted LENF at birth and short-term
      ambulatory status. However, fMMC toddlers continue to demonstrate deficits in
      movement coordination that are characteristic for children with spina bifida.

PMID- 19174611
TI  - Incidence of traumatic peripheral nerve injuries and amputations in Sweden
      between 1998 and 2006.
AB  - BACKGROUND: To define the epidemiological pattern of nerve injuries and traumatic
      amputations in Sweden, 1998-2006, and investigate possible targets for emerging
      neural engineering and neuroprosthetic technologies. METHODS: The Swedish
      Hospital Discharge Register was used as the information base, including data from
      all public inpatient care, excluding outpatient data. ICD-10 codes were used to
      classify nerve injuries and traumatic amputations of high incidence levels or
      inpatient care time. Selected codes, causative factors, age and gender
      distribution were discussed in detail, and potential targets for tailored
      solutions were identified. RESULTS: Incidence rate was determined as 13.9 for
      nerve injuries and 5.21 for amputations per 100,000 person-years. The majority of
      injuries occurred at the wrist and hand levels, although it could be concluded
      that these are often minor injuries requiring less than a week of
      hospitalization. The single most care-consuming nerve injury was brachial plexus
      injury, constituting on average 68 injuries and 960 hospital days annually. When
      minor amputations of fingers and toes were disregarded, the most frequent site of
      amputation was between the knee and ankle (24 patients/year). CONCLUSIONS: Based
      on an analysis of incidence and care time, we find that brachial plexus injuries
      and lower leg amputations should be the primary targets of new technologies.

PMID- 19174612
TI  - Negative prognostic impact of the coexpression of epidermal growth factor
      receptor and c-erbB-2 in locally advanced cervical cancer.
AB  - OBJECTIVE: The objective was to determine the impact of the coexpression of
      epidermal growth factor receptor (EGFR) and tumor marker c-erbB-2 on disease-free
      survival (DFS) and pelvic relapse-free survival (PRFS) in patients with locally
      advanced cervical cancer (LACC) receiving concurrent chemoradiotherapy. METHODS:
      The expression of EGFR and c-erbB-2 was assessed by immunohistochemistry, which
      was centralized and blinded to outcome. Univariate and multivariate analyses were
      used to evaluate the impact of EGFR and c-erbB-2 on DFS and PRFS. RESULTS: 170
      patients with LACC were included and received concurrent chemoradiotherapy. 25
      (15%) biopsies were considered EGFR and c-erbB-2 positive; 100 (59%) were either
      EGFR or c-erbB-2 positive, and 45 (26%) were EGFR and c-erbB-2 negative. The 3-
      and 5-year DFS was 39% each for EGFR- and c-erbB-2-positive patients, 54 and 49%,
      respectively, for EGFR- or c-erbB-2-positive patients, and 76 and 72%,
      respectively, for EGFR- and c-erbB-2-negative patients (p = 0.006). EGFR- and c
      erbB-2-positive tumors were significantly associated with a decrease in PRFS
      (hazard ratio, HR, 3.99; 95% confidence interval, CI, 1.44-11.05, p = 0.007), and
      DFS (HR 2.9; 95% CI, 1.26-6.66, p = 0.01). CONCLUSION: Patients with LACC
      coexpressing EGFR and c-erbB-2, and treated with concurrent chemoradiotherapy,
      had a worse clinical prognosis with shorter DFS and PRFS.

PMID- 19174613
TI  - Prevalence of single and multiple human papillomavirus types in cervical cancer
      and precursor lesions in Hubei, China.
AB  - OBJECTIVE: The objective of this study was to establish the prevalence and type
      distribution of human papillomavirus (HPV) in cervical cancer and cervical
      intraepithelial neoplasia (CIN) in Hubei, China. METHODS: A total of 112 patients
      with cervical cancer and 60 CIN II-III samples were obtained from women
      undergoing biopsy or surgery. HPV and typing were examined by the polymerase
      chain reaction (PCR) and sequencing. RESULTS: HPV DNA was detected in 105
      patients with cervical cancer (93.75%), HPV 16 being detected in 91 (81.25%)
      cases, and HPV 58 in 7 (6.25%) cases. HPV DNA was detected in 50 patients with
      CIN II-III (83.33%), HPV 16 being detected in 37 (61.67%) cases, HPV 58 in 5
      cases (8.33%). HPV 18 was not common in this study. About 11% cervical cancer and
      8.33% CIN II-III specimens exhibited multiple infections (p = 0.79). CONCLUSION:
      The high prevalence of HPV 16 in Hubei, China, deserves attention as it has
      important implications for the usefulness of vaccine and the choice of diagnostic
      methods.

PMID- 19174614
TI  - Efficacy of vitrectomy and internal limiting membrane removal for macular edema
      associated with branch retinal vein occlusion.
AB  - AIM: To compare the results of vitrectomy with internal limiting membrane (ILM)
      peeling to that without ILM peeling for macular edema associated with branch
      retinal vein occlusion (BRVO). METHODS: The medical records of 47 eyes of 47
      patients with BRVO-associated macular edema were examined. To treat the macular
      edema, a posterior vitreous detachment (PVD) was created, and the ILM was removed
      in 13 eyes (ILM-removed group), whereas a PVD was created and the ILM was not
      removed in 34 eyes (ILM-preserved group). The best-corrected visual acuity (BCVA)
      and the optical-coherence-tomography-determined foveal thickness were obtained
      preoperatively and at 6 months postoperatively. RESULTS: The mean postoperative
      BCVA was significantly better than the preoperative BCVA in both the ILM-removed
      and in the ILM-preserved groups (p = 0.0017 and p = 0.0002, respectively). The
      fovea was significantly thinner at 1 month after surgery in both groups (p =
      0.0007 and p < 0.0001, respectively). The postoperative improvement of the mean
      BCVA and the foveal thickness were not significantly different for the two groups
      at any postoperative period. CONCLUSIONS: Because there was no significant
      difference in the improvement of BCVA between the two groups at 6 months
      postoperatively, there may be no additional benefit in removing the ILM for BRVO
      associated macular edema.

PMID- 19174615
TI  - Score for Neonatal Acute Physiology and Perinatal Extension II as a predictor of
      retinopathy of prematurity: study in 304 very-low-birth-weight preterm infants.
AB  - AIM: To evaluate the use of the Score for Neonatal Acute Physiology and Perinatal
      Extension (SNAPPE-II) at admission to predict the development of retinopathy of
      prematurity (ROP) among very-low-birth-weight preterm babies. METHODS: A
      prospective cohort study included 304 infants screened for ROP from July 2004 to
      October 2007. The main outcomes were the development of any stage ROP and severe
      ROP. The main variable was the SNAPPE-II obtained at admission. Seventeen risk
      factors for ROP were studied by univariate analysis (chi(2) and Student's t
      test). A simple descriptive analysis was used for the SNAPPE-II (mean, median,
      standard deviation and interquartile range: p25-p75). Logistic regression and
      receiver-operating characteristic (ROC) curve were calculated for SNAPPE-II.
      Ophthalmological examinations started at the 6th week of life and were repeated
      until the 45th week of corrected gestational age (GA). RESULTS: The mean GA and
      mean birth weight of the whole cohort were 30.3 weeks (+/-2.2) and 1,209.2 g (+/
      277.7), respectively. The median SNAPPE-II among non-ROP and ROP patients were
      6.0 and 15.0, respectively (p = 0.001). When compared with severe ROP patients
      (25.0) there was also a significant difference (p = 0.003). After logistic
      regression, the SNAPPE-II adjusted odds ratio for ROP was 1.024. The area under
      the ROC curve was 0.62 (95% confidence interval: 0.55-0.70, p < 0.001). The best
      discriminative cutoff value was 8.5 (sensitivity: 68%; specificity: 54%; positive
      predictive value: 37.3%; negative predictive value: 80.6%). CONCLUSIONS: The
      SNAPPE-II values at admission were significantly higher among babies with ROP,
      suggesting a positive association between higher scores with the development of
      ROP, but after adjusted logistic regression and ROC curve results, the SNAPPE-II
      scores at admission did not enhance the assessment of risk for ROP.

PMID- 19174616
TI  - Antiplatelet activity of Allium ursinum and Allium sativum.
AB  - OBJECTIVES: Garlic (Allium sativum) has a well-established reputation as a
      protective agent against cardiovascular disease, while nearly nothing is known
      about its cousin Allium ursinum. The aim of this study was to evaluate the
      antiaggregatory mechanism of garlic and to compare the effects of A. ursinum and
      A. sativum. METHODS: In a prospective study, extracts were prepared from A.
      sativum powder made from fresh A. sativum bulbs and fresh A. ursinum leaves by
      maceration. The extracts were characterized by thin layer chromatography. Their
      in vitro effects on human platelet aggregation were examined by light
      transmission aggregometry after induction by adenosine diphosphate (ADP),
      collagen, A23187, epinephrine and arachidonic acid (ARA) in platelets from
      healthy volunteers. RESULTS: A. ursinum and A. sativum exert similar
      antiaggregatory effects: they inhibit platelet aggregation induced via the ADP
      pathway and to a lesser extent aggregation induced by epinephrine, whereas ARA-,
      collagen- and A23187-induced aggregation was not affected. It became clear that
      the alcoholic extract of A. ursinum is the potent form, while the aqueous extract
      exerted an unspecific activity. The effects were strictly dose related. A.
      ursinum and A. sativum extracts exhibited similar potencies. CONCLUSION: Both A.
      ursinum and A. sativum exert antiaggregatory effects. Garlic extracts are acting
      by inhibition of the ADP pathway; their mechanisms of action are comparable to
      that of the clinically used drug clopidogrel. The pharmacologically active
      component of the extracts appears to be lipophilic rather than hydrophilic, but
      the precise chemical substance is still unknown. This is the first report on the
      antiplatelet activity of A. ursinum.

PMID- 19174617
TI  - Haloperidol versus haloperidol plus ondansetron for the prophylaxis of
      postoperative nausea and vomiting after ophthalmologic surgery.
AB  - INTRODUCTION: In this prospective, randomized, and double-blinded study we
      investigated the efficacy of haloperidol (10 microg/kg) and the combination of
      haloperidol (10 microg/kg) with ondansetron (0.1 mg/kg) for the prophylaxis of
      postoperative nausea and vomiting (PONV) after ophthalmologic surgery. METHODS:
      60 patients (ASA status 1-3) with risk factors for PONV (female, non-smoker,
      motion sickness or PONV in history, opioids for postoperative analgesia)
      undergoing retinal or strabismus surgery were included into the study and
      randomised to the haloperidol group (H-Group) or the haloperidol-ondansetron
      group (H/O-Group). 20 min before the end of anaesthesia the study medication was
      given. Nausea, vomiting, pain scores, and adverse events were assessed
      postoperatively over 24 h. RESULTS: The incidence of PONV was lower for the H/O
      Group (23 vs. 57% for the H-Group). Especially the incidence of vomiting was
      reduced for the H/O-Group (7 vs. 27% in the H-Group). No significant differences
      could be detected regarding adverse events. CONCLUSION: The single use of
      haloperidol for the prophylaxis of PONV is doubtful. Better results were obtained
      with the combination therapy of haloperidol with ondansetron, especially for
      vomiting.

PMID- 19174618
TI  - Staged Gamma Knife radiosurgery after tailored surgical resection: a novel
      treatment paradigm for glomus jugulare tumors.
AB  - OBJECT: Although benign and slow growing, glomus jugulare tumors can be locally
      aggressive because of their proximity to lower cranial nerves and major vascular
      structures. Surgical resection frequently leads to complications, and
      radiosurgery alone often does not relieve symptoms. We report a novel treatment
      paradigm of tailored surgical resection followed by staged radiosurgery that
      allows for tissue diagnosis and immediate improvement of symptoms and tumor
      control without the morbidity of radical surgical resection. METHODS: Five
      patients with glomus jugulare tumors and contraindications to extensive surgery
      each underwent an outpatient otologic procedure to resect the portion of the
      tumor in the middle ear and mastoid with no attempt to remove tumor in the
      jugular bulb. Each patient returned 2-5 months later for Gamma Knife radiosurgery
      to the remainder of the tumor, which consisted of one 15-Gy dose prescribed to
      the 50% isodose curve. Patients were followed through outpatient visits and
      surveillance MR imaging for up to 3 years. RESULTS: All patients were
      successfully treated as outpatients. Each had improvement or resolution of
      pulsatile tinnitus and otalgia and preserved or improved hearing. One patient
      developed a delayed facial palsy prior to radiosurgery that resolved completely;
      there were no other changes in cranial nerve function after either procedure.
      Tumor volume was stable or reduced in all patients at most recent follow-up, and
      there were no immediate or delayed complications. CONCLUSIONS: Staged outpatient
      microsurgical and radiosurgical therapy for glomus jugulare tumors in the
      symptomatic patient is safe and yields favorable results regarding tumor size,
      tinnitus, hearing and cranial nerve status.

PMID- 19174620
TI  - Subthalamic nucleus stimulation does not cause deterioration of preexisting
      hallucinations in Parkinson's disease patients.
AB  - BACKGROUND: Among the neuropsychiatric symptoms in Parkinson's disease (PD)
      patients, hallucination can result from the disease itself or medical treatment.
      Hallucination associated with subthalamic nucleus stimulation (STN-DBS) has been
      reported; however, it is still unclear whether PD patients with a history of
      hallucination are appropriate candidates for STN-DBS or not. AIMS: We
      investigated the effect of STN-DBS on preexisting hallucination associated with
      advanced PD. METHODS: Eighteen STN-DBS patients were investigated
      retrospectively. The severity of hallucination was assessed by the thought
      disorder score on the Unified Parkinson's Disease Rating Scale (UPDRS, part 1
      item 2) in the patients' interviews; the score 6 months after the initiation of
      STN-DBS was compared with the highest score throughout the preoperative history
      and the score 2 weeks before surgery. RESULTS: Hoehn-Yahr stage and motor score
      (UPDRS part 3) were significantly improved following STN-DBS. Six months after
      the initiation of STN-DBS, the severity of hallucination, assessed by thought
      disorder score, did not increase, but rather decreased compared with the
      preoperative level (p < 0.05 by McNemar's test). The daily levodopa equivalent
      dose was increased in 2 patients without the development of hallucination. On the
      other hand, anti-parkinsonian drugs were totally withdrawn in 1 patient, but
      without improvement of hallucination. CONCLUSIONS: Our findings indicate that STN
      DBS surgery does not always lead to deterioration of preexisting hallucination in
      PD. In advanced PD, hallucination involves a multifactorial pathogenesis and a
      history of hallucination is not a contraindication to STN-DBS surgery.

PMID- 19174621
TI  - Isosurface-based generation of hulls encompassing neuronal pathways.
AB  - BACKGROUND: Diffusion tensor imaging provides information about the location of
      white matter tracts within the human brain. For neurosurgery, this imaging
      technique is of major interest in order to minimize the risk of postoperative
      neurological deficits. In preoperative planning, fiber tracking algorithms based
      on streamline propagation are used in order to reconstruct major fiber tracts.
      The resulting streamline bundles approximate the course of the underlying white
      matter structures and indicate their shape and location in 3 dimensions as well
      as the spatial relation with respect to surrounding anatomy. However, for
      intraoperative application in combination with the neuronavigation system, these
      streamline representations are not adequate. Hulls encompassing the streamline
      bundles are necessary, since the boundary curves of hulls can be superimposed on
      the operating room (OR) microscope view for guidance in neurosurgery. METHODS: In
      this work, we present a novel hull approach which is based on rasterization and
      isosurface extraction, combined with surface filtering techniques. The advantages
      of this approach are its robustness and the possibility to control the tightness
      of wrapping. RESULTS: The approach makes it possible to generate precise hulls
      for different tract systems, which can be used as a basis for intraoperative
      visualization in the OR microscope. Distance measurements further confirm the
      accuracy of the hulls.

PMID- 19174619
TI  - Induction of bradykinesia with pallidal deep brain stimulation in patients with
      cranial-cervical dystonia.
AB  - BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is
      an effective and well-tolerated treatment for idiopathic generalized dystonia.
      More recently, it has been applied as a treatment for focal and segmental
      dystonias. This patient population offers an opportunity to study the effects of
      alteration of pallidal outflow on previously normal limb function. METHODS: We
      sought to retrospectively characterize the extent of novel GPi DBS-induced
      adverse motor effects in patients with adult-onset cervical and cranial-cervical
      dystonia using a questionnaire, and compared the findings to dystonia improvement
      as measured by standard scales. RESULTS: Despite significant improvement in
      dystonia (65% in mean Burke-Fahn-MarsdenDystonia Rating Scale motor score, p <
      0.005, and 59% in mean Toronto Western Spasmodic Torticollis Rating Scale score,
      p < 0.008), slowing and difficulty with normal motor function was reported in
      previously nondystonic extremities in 10 of 11 patients. Symptoms were common in
      both upper and lower extremities and included new difficulties with handwriting
      (82%), getting up from a chair or in/out of a car (73%), and walking (45%), and
      were not associated with aberrant lead placement near the internal capsule.
      CONCLUSION: Although GPi DBS was shown to be effective in these patients, the
      influence of GPi DBS on nondystonic body regions deserves further investigation.

PMID- 19174622
TI  - Radiosurgery for desmoplastic melanoma of the head and neck using the Leksell
      Gamma Knife Perfexion technology: a case report.
AB  - A 44-year-old male developed chronic cancer pain caused by a progressive
      desmoplastic melanoma involving the mandibular division of the trigeminal nerve.
      The patient had failed local resection, conformal radiation therapy and
      chemotherapy, but was eligible for stereotactic radiosurgery using a new
      technology. Intraoperative stereotactic magnetic resonance and computed
      tomography imaging were fused to define the tumor volume and to create a
      conformal radiosurgery dose plan. The radiosurgery target volume was 8.6 ml. A
      marginal dose of 17 Gy at the 50% isodose was prescribed. The entire procedure
      was performed on an outpatient basis. The Leksell Gamma Knife Perfexion
      technology increases the spectrum of treatable pathologies located in the cranial
      base and head and neck regions.

PMID- 19174623
TI  - [The interpretation of suicide by gender in late Joseon Dynasty: around cases of
      suicide in "Trial Document"].
AB  - This paper focuses on cases of suicide in "Trial Document (Simrirok)" which was
      published in Jeongjo's reign, and how to understand suicide cases in social
      context. Even though "Trial Document" is limited historical material to report
      for King, it is very useful to examine not only suicide case of those times but
      also the elite's recognition about suicide. Especially in this paper, the
      important point is not 'why and how did a suicide kill himself or herself' but
      'how people did understand about suicide or a suicide'. In other words, the key
      point of this paper is 'discourse' of suicide. There are so multifarious suicide
      cases in "Trial Document" and the reasons of suicide are also multifarious.
      However, 'Trial Document' is worthy of note because it is the document which was
      recorded trial processes. In these processes, decision on 'suicide or murder' was
      the most essential point. So there were arguments on discerning whether a victim
      committed suicide or a murderer counterfeited a victim's suicide. The important
      thing was not only real evidence in these arguments. Belief, 'it is acceptable
      reason for suicide', was very important as a social context. One of the important
      criterions was 'gender' to Jeoseon's elite. In spite of cases' similarities, the
      interpretation was completely different by gender. Men's suicide was understood
      as 'a foolish act' by the elite because they thought that 'normal man' would not
      commit suicide. Moreover, there were particular women's suicide cases which could
      not happen to men. The reason of these suicides was 'chastity'. The cases were
      also 'interpreted' by the people alive. These interpretation was based on the
      value judgement. And another important criterion was class. The elite had given a
      prize to the women who suicided directly after their husbands' death. The elite
      themselves, however, did not suicide so much as the common people did. This
      contradiction shows that suicide is not a personal choice absolutely. This paper
      searches into the meaning of suicide in late Joseon society, and look into
      'gender' as the most important criterion of judgement.

PMID- 19174624
TI  - [Medical doctor Lee Hyeon Yang's writings in Gokcheongsago].
AB  - Medical doctors in the Chosun Dynasty read Chinese literature of high level in
      order to take the medical civil service examination, but there are not many
      extant writings of theirs except some medical books. Middle class people's
      selections of poems such as Haedongyuju, Sodaepungyo, Pungyosokseon and
      Pungyosamseon were published, and among the list of the writers, those who were
      identified as medical doctors were Park Gun, Baek Heung jeon, Shin Myeong hee,
      Shin Hee myeong, Oh Chang ryeol, Yoo Dong yeok, etc. Even their works are not
      many, and this suggests that doctors' writing was not active except for medical
      books. Lee Hyeon yang (1783-1852), the author of Gokcheongsago, was born the only
      son of Lee Jaewoo (1750-1808), an acupuncturist at the Lee family from Ansan,
      which was an influential middleclass family. His pen name was changed from
      Gokcheong to Anrakwa, Yongheon and Gyeongsudang, and for each pen name, he wrote
      a foreword explaining the origin of the name and his resolution. The Lee family
      from Ansan produced 20 medical officials through eight generations from Lee Yoon
      yeong in the 7th generation to Lee Myeong ryun in the 15th generation. He learned
      medicine, his family occupation, diligently and passed the medical civil service
      examination in 1803 when he was 21. In addition, he studied Confucian scriptures
      enthusiastically and left many writing along with medical books. Based on the
      forewords in his anthology Gokcheongsago, there are eight writings of his as
      follows in chronological order: Suseongpyeongam (1798), Cheongimiyo (1799),
      Euihakjeongwon (1801), Gwangjebiyo(five volumes, 1810), Wonbyeonggiyo (1819),
      Bonchojeongeui(1826), Euiyakcheongji (1838), and Yeonghwaji (1843). He wrote not
      only medical books but also traditional Chinese texts in different styles. In the
      180pages transcription, he as a medical doctor showed various writing styles
      based on Confucianism including 22 prologues and epilogues, 9 diaries,
      discussions and opinions, 2 biographies, 5 letters, 10 memorial addresses and
      condolence messages, and 8 miscellaneous writings. His writing attitude was
      different among the periods when preparing for the medical civil service
      examination, when acting as a medical doctor, and when working as a magistrate,
      and it shows medical doctors' life in the 18th and 19th centuries.

PMID- 19174625
TI  - [Physical anthropology studies at Keijo Imperial University Medical School].
AB  - Medical research during the Japanese Colonial Period became systematic and active
      after the Keijo Imperial University Medical School was established in 1926.
      Various kinds of research were conducted there including pharmacological,
      physiological, pathological and parasitological research. The Keijo Imperial
      University was give a mission to study about Korea. Urgent topics for medical
      research included control of infectious diseases, hygiene and environmental
      health that might have affected colonizing bodies of the Japanese as well as the
      colonized. The bodies of Koreans had been studied by Japanese even before the
      establishment of the University. The Keijo Imperial University research team,
      however, organized several field studies for physical anthropology and blood
      typing research at the national scale to get representative sampling of the
      people from its north to its south of the Korean peninsula. In the filed, they
      relied upon the local police and administrative power to gather reluctant women
      and men to measure them in a great detail. The physical anthropology and blood
      typing research by the Japanese researchers was related to their eagerness to
      place Korean people in the geography of the races in the world. Using racial
      index R.I.(= (A%+AB%)/(B%+AB%)), the Japanese researchers put Koreans as a race
      between the Mongolian and the Japanese. The preoccupation with constitution and
      race also pervasively affected the medical practice: race (Japanese, Korean, or
      Japanese living in Korea) must be written in every kind of medical chart as a
      default. After the breakout of Chinese-Japanese War in 1937, the Keijo Imperial
      University researchers extended its physical anthropology field study to
      Manchuria and China to get data on physics of the people in 1940. The Japanese
      government and research foundations financially well supported the Keijo Imperial
      University researchers and the field studies for physical anthropology in Korea,
      Manchuria and China. The physical anthropology research was actively conducted
      hand in hand with imperialistic expansion, and driven by zeal for measuring the
      body.

PMID- 19174626
TI  - [Life and medical activities of Yun Ti Wang].
AB  - Yun Ti Wang studied medicine in England, different from other Korean medical
      doctors in early days. Yun, who entered medical school at Glasgow University in
      England in March 1919, graduated with a Bachelor of Medicine in October 1925,
      along with an England medical license. Yun began working as an instructor at
      Severance Medical College from November 1927, and received Doctor of Medicine
      from the College of Obstetricians and Gynecologists at Kyoto Imperial University
      in August 1936. After the Liberation, Yun began working as a faculty member at
      the medical school at Seoul University, and he also worked as a Chief of the
      Second Medical Clinic of the school from 1946. Yun made a great effort in order
      to build an integrated committee, eventually contributing to the launching of
      Joseon Medical Associates in 1947. He was also elected as a first president at
      Joseon Obstetrics and Gynecology Associates, which was organized at the same year
      as the Joseon Medical Associates. Yun entered military as an army surgeon in
      April 1949 and has worked there until he was appointed as a principal at the Army
      Medical School in September 1953. His contributions to the development of
      military medical services include the following: expansion of medical facilities
      in army, stable system of workforce in military medical service, launching of
      Medical Aid and establishment of Department of Medical Care, and introduction of
      new medical technologies in anesthesiology and neurosurgery, etc. The career of
      Yun can be largely divided into the field of gynecology and military medical
      services. In the gynecological field, Yun contributed to the settlement of
      obstetrics in Korea, by taking in charge of the obstetrics class at Severance
      following medical missionaries. As for the military medical services, he has
      contributed to the establishment of military medical system as well as to the
      opening of new academic areas. The impact of his activities on the establishment
      of military medical services is especially significant, since it was a field that
      no Korean citizens had access to during the colonization era.

PMID- 19174627
TI  - [Medical doctors' independence movement during the Japanese colonial period].
AB  - There are approximately 10,000 people who have been identified as men of merit
      for independence movement by the Ministry of Patriots and Veterans Affairs in
      Korea. Currently, January of 2008, it is assumed that there are 156 doctors
      (medical school students included) had participated in independence movement,
      among them, 71 people have received the rewards from the government with the
      honor of independence movement as a doctor or medical school student. However,
      there are still 85 doctors have not received any rewards from the government
      despite their participation in independence movement. Korean doctors and medical
      students participated in independent movement through many ways in domestic and
      foreign country during the Japanese colonial period. They made use of their
      doctor license, and occasionally took part in independent movement as ordinary
      people. They not only had acted as politicians, diplomats, and medical officers,
      but also supported medical service, donation campaign, social movement, and
      educational movement for independent movement against Japanese colonial rule.

PMID- 19174628
TI  - [Trade, wars and the venereal disease: VD epidemic and control of Korea in the
      late nineteenth and early twentieth century].
AB  - This paper examines the spread of venereal disease from the Opening of Korea to
      the early Japanese colonial period. It focuses on the formation and expansion of
      Japanese settlement in Korea, the influence of wars, and the state control of VD.
      The Opening of Korea made the foreign settlement, and Japanese licensed
      prostitution flourished in Japanese settlement. According to the First Annual
      Report of the Korean Government Hospital (1886) and Gyelimuisa (1887), VD
      patients occupied 18.3% of outpatients in Jejungwon hospital of Seoul and 8.9% of
      outpatients in Busan hospital. Directly after the Opening of Korea, Korean
      people's VD became lesser critical than Japanese people's VD. But the expansion
      of Japanese settlement and outbreak of two wars such as Sino-Japanese War and
      Russo-Japanese War made worse Korean people's VD. According to the Residency
      General resources (1904-1909), syphilis patients was registered in 0.8-6.6%
      (average 3.6%). If it add to gonorrhea and chancroid patients which often could
      not be found out by the naked eyes, the number of VD patients will be increase.
      Ji Seok-yeong (1855-1935), the earliest smallpox vaccinarian in Korea, asserted
      the need of VD control. Though he warned men bought sex as well as prostitutes
      became the main culprit of VD diffusion, he supported licensed prostitution
      because of realistic possibility. The Great Han Empire (1897-1910) tried to
      control the lower grade whore, and gathered prostitutes in some area by police
      power. After Japanese annexation of Korea, while Japanese has gradually decreased
      in VD patients, Korean has gradually increased in VD patients.

PMID- 19174629
TI  - Heparin-induced thrombocytopenia: your questions answered.

PMID- 19174631
TI  - Credentialing and privileging for advanced practice nurses.

PMID- 19174632
TI  - Integrating healthy work environment standards into undergraduate curriculums.

PMID- 19174633
TI  - Pediatric evidence-based practice: using the best available evidence to improve
      pediatric outcomes.

PMID- 19174634
TI  - Update on ventricular assist device technology.
AB  - Ventricular assist devices are an important component in the arsenal of therapies
      to support the failing heart. This article provides an update on the variety of
      pulsatile, centrifugal, and axial-flow devices available in the United States.
      Common indications such as Bridge to Recovery and Bridge to Transplant are
      explored, as are the emerging indications Destination Therapy, Bridge to
      Decision, and Bridge to Bridge. Ventricular assist devices as support during high
      risk percutaneous coronary intervention and the devices that can be rapidly
      deployed for this support are included. Clinical aspects of patient care
      including common complications, psychosocial concerns, and ethical considerations
      are reviewed.

PMID- 19174637
TI  - Strategies for success: orienting to the role of a clinical nurse specialist in
      critical care.
AB  - Successful integration of a new clinical nurse specialist within an organization
      optimizes the safe, cost-effective implementation of evidence-based practice and
      research. This article provides strategies and information to support the
      clinical nurse specialist during his or her role transition, highlights
      opportunities and challenges to the role, and provides examples of orientation
      and performance tools that can assist in a successful orientation process.

PMID- 19174636
TI  - Argatroban therapy in heparin-induced thrombocytopenia.
AB  - Patients who develop heparin-induced thrombocytopenia (HIT) are at increased risk
      for morbidity and mortality if the disorder is not recognized and treated early.
      Upon initial suspicion of HIT, providers should promptly discontinue all heparin
      products and initiate an alternative form of anticoagulation without waiting for
      diagnostic test results confirming the presence of HIT antibodies. The direct
      thrombin inhibitor, argatroban (Argatroban), is a reasonable alternative
      anticoagulant in patients with HIT, based on its proven safety and efficacy, ease
      of use, and consistent response rate between individuals. Further clinical trials
      are warranted to evaluate and expand the use of argatroban in other thrombotic
      states.

PMID- 19174638
TI  - Nurse manager orientation.
AB  - On the basis of the principles of management and leadership, our organization has
      worked over the years to formalize the orientation program for new nurse
      managers. This program meets the needs of new nurse managers and responds to
      today's complex health care system needs. This article describes the components
      of a nurse manager orientation program for the novice nurse manager and methods
      for evaluating nurse manager effectiveness.

PMID- 19174639
TI  - Clinical faculty: tips for joining the ranks.
AB  - There has never been a more urgent time for clinically expert nurses to consider
      the clinical faculty role. Whether they are making a full-time "leap" into
      academia or combining a successful staff nurse role with a part-time clinical
      teaching position, nurses should consider teaching as a good career move.
      Practical tips and resources are described for making the transition into a
      clinical faculty role a smooth one.

PMID- 19174640
TI  - Orientation program for hospital-based nurse practitioners.
AB  - The transition from student to practicing clinician is often a challenging and
      difficult period for many nurse practitioners. Newly graduated nurse
      practitioners commonly describe feelings of inadequacy in assuming clinical
      responsibilities, lack of support by team members, unclear expectations for the
      orientation period, and role isolation. This article describes the formal nurse
      practitioner orientation program implemented at the University of Maryland
      Medical Center, a large urban academic medical center, to facilitate the
      transition of new nurse practitioners into the workforce. This comprehensive
      program incorporates streamlined administrative activities, baseline didactic and
      simulation-based critical care education, ongoing and focused peer support,
      access to formalized resources, and individualized clinical preceptor programs.
      This formalized orientation program has proven to be one of the key variables to
      successful integration of nurse practitioners into our acute care clinical teams.

PMID- 19174641
TI  - Go to the head of the class: clinical educator role transition.
AB  - Facing that first day as an educator who is new to the role or new to the
      institution can be daunting. An organized orientation program can facilitate
      educators' assimilation into their role and provide assistance in understanding
      their duties and responsibilities. Orientation should be individualized according
      to the learning needs of the new educator and should provide information on
      hospital expectations, structure, and environment. A part of the educator's
      orientation should focus on understanding educational processes and resources
      available within the new institution. A well-structured and well-designed
      orientation process facilitates the development of the clinical educators so they
      truly can go to the head of the class.

PMID- 19174642
TI  - Primer for successful grant writing.

PMID- 19174643
TI  - Ethical discernment and action: the art of pause.

PMID- 19174644
TI  - Understanding atrioventricular blocks, part II: high-grade and third-degree
      atrioventricular blocks.

PMID- 19174645
TI  - Ethical approval for studies involving human participants: academic medicine's
      new policy.

PMID- 19174646
TI  - More about struggling students.

PMID- 19174647
TI  - The price of changing the status quo.

PMID- 19174650
TI  - More about struggling students.

PMID- 19174652
TI  - Another view of the white coat ceremony.

PMID- 19174653
TI  - Should quality improvement projects require IRB approval?

PMID- 19174654
TI  - A skills-based approach to teach clinical ethics.

PMID- 19174655
TI  - Commentary: Knowing it when we see it: reflections on pornography.
AB  - This commentary asks, of what contemporary use is the excavation of a specific
      incident of sexually intimidating and otherwise inappropriate behavior in medical
      education's history? The question is posed in response to the accompanying
      article by Halperin detailing the publication and critical reception of an
      anatomy textbook that adopted a demeaning attitude toward women and featured
      pinup style photographs of nude women. The author contends that the generational
      context of feminist response to this incident and others like it is critical in
      shaping the current discussion. Today's third-generation feminists recognize the
      injustice of exploitative or offensive behaviors, but because of a fear of
      retaliation or negative consequence, they may nonetheless decline to respond in
      an official or whistle-blowing capacity-despite efforts to normalize appropriate
      faculty-learner interactions and to provide safe reception for those affected by
      abuses of power or authority. Revisiting an incident such as the one Halperin
      recounts reminds readers of both genders and all career stages that violations of
      professional mores between teacher and learner still occur and that the price of
      speaking up remains high.

PMID- 19174656
TI  - Commentary: Those who do not learn from history are doomed to repeat it.
AB  - In this commentary, the author asks, can educators learn from being reminded of
      moments of poor judgment or inappropriate behavior in the history of medical
      education, or should these incidents not be revived and revisited? The question
      is posed in relation to the accompanying article in this issue by Halperin, which
      examines the publication of a medical textbook that featured pin-up style photos
      of women but not men. Both in the past and now, attitudes and behaviors can be
      found within medical education that have helped to sustain cultural
      misunderstanding and bias. It may be difficult to become aware of these attitudes
      and the ways they can infect teaching, thus detracting from good care of
      patients. A more recent example from the author's experience is discussed,
      regarding physician bias toward treating patients with HIV/AIDS. Readers are
      reminded that medicine not only exists in the context of social mores and
      customs, but helps create them. Examining the past can help to cultivate
      awareness of such inappropriate bias and generate strategies for resistance.

PMID- 19174657
TI  - Commentary: Out of the silence: confronting depression in medical students and
      residents.
AB  - In this commentary, the authors reinforce the call to action made in the
      accompanying reports by Goebert et al and Dunn et al. Depression among medical
      students and residents is a continuing and worrisome phenomenon; its chronic
      nature has long-term and compounding effects on trainees. Yet, barriers exist to
      appropriate care seeking, such as inadequate education about causes, effects, and
      treatment; unwillingness to take the needed time; limited financial resources to
      pay for care; and concerns over confidentiality, stigma, or adverse effects on
      residency application or licensability. Each of these barriers, the authors
      contend, can be circumvented. Moreover, given the cost of unrecognized or
      untreated depression among the health care workforce, removal of the barriers
      reflects both moral and practical necessities. The authors discuss successful
      prevention and treatment plans at some medical schools and academic health
      centers (AHCs), as well as initiatives by the American Foundation for Suicide
      Prevention geared specifically to the nation's medical trainees and physicians.
      Finally, strong leadership is encouraged in order to remove the barriers to
      recognizing and treating depression and to change the culture of medicine that
      contributes to and/or stigmatizes depression among its members.The authors
      outline the chronic nature of depression and discuss its possibility for long
      term impacts on trainees. Given these conditions, the leadership of the nation's
      schools of medicine and AHCs.

PMID- 19174658
TI  - Defining the role of University of Kentucky HealthCare in its medical market--how
      strategic planning creates the intersection of good public policy and good
      business practices.
AB  - In response both to national pressures to reduce costs and improve health care
      access and outcomes and to local pressures to become a top-20 public research
      university, the University of Kentucky moved toward an integrated clinical
      enterprise, UK HealthCare, to create a common vision, shared goals, and an
      effective decision-making process. The leadership formed the vision and then
      embarked on a comprehensive and coordinated planning process that addressed
      financial, clinical, academic, and operational issues. The authors describe in
      depth the strategic planning process and specifically the definition of UK
      HealthCare's role in its medical marketplace. They began a rigorous process to
      assess and develop goals for the clinical programs and followed the progress of
      these programs through meetings driven by data and attended by the organization's
      senior leadership. They describe their approach to working with rural and
      community hospitals throughout central, eastern, and southern Kentucky to support
      the health care infrastructure of the state. They review the early successes of
      their strategic approach and describe the lessons they learned. The clinical
      successes have led to academic gains. The experience of UK HealthCare suggests
      that good business practices and good public policy are synergistic.

PMID- 19174659
TI  - Governance of the academic health center: striking the balance between service
      and scholarship.
AB  - Academic health centers (AHCs) rank among the most complex organizations.
      Spanning the domains of university, clinical practice, hospital, and research,
      AHCs encompass a range of strikingly different business models, each with its own
      economic potential. The ability to bring these diverse enterprises actively
      working together has been the unique strength of the AHC as a vehicle of patient
      care, education, and discovery. Unfortunately, the AHC has also proved at times
      to be a frustrating organizational matrix of indecision wrought by different aims
      and distributed influence, presenting substantial challenges to the success of
      these institutions. The question of how best to organize the fiduciary and
      executive management structures of the AHC continues to be the subject of much
      interest to those trustees responsible for these complex institutions. Although
      the question of what is the best governance model for an AHC is sometimes
      approached in simple terms of "one leader, or multiple," success is more likely
      defined by how well other critical factors are organized and managed. These
      include considerations of governance, including selection and education of key
      trustees, their ability to access key data for their specific institution and the
      AHC as a whole, performance evaluation of the operating executives with respect
      to both specific institutional criteria and those for the AHC as a whole, and
      management oversight by boards across the AHC. When more than one governing body
      is involved, joint participation of boards and key executives is recommended for
      selected aspects of these processes.

PMID- 19174660
TI  - Can hospital rankings measure clinical and educational quality?
AB  - BACKGROUND: A relative dearth of relevant data hampers efforts to demonstrate a
      link between educational and clinical quality and may preclude residency
      applicants from identifying programs with the best clinical outcomes. Existing
      clinical rankings could fill this gap if they are based on sound judgments about
      quality. METHOD: To explore the potential of the U.S. News & World Report
      "America's Best Hospitals" clinical rankings in measuring the quality of clinical
      and learning environments, the author systematically reviewed the U.S. and
      Canadian literature for 1975 through 2007 regarding quality indicators and
      teaching hospitals. Individual data elements of the rankings were examined to
      assess the extent to which they included accepted measures of clinical
      performance. RESULTS: A total of 187 articles met the inclusion criteria of
      addressing clinical quality criteria relevant to the rankings and quality
      assessment in teaching hospitals. Statistical examination of the data underlying
      the rankings and their relationship with measures of educational and clinical
      quality showed the rankings are largely based on institutional "prestige." Ranked
      clinical programs and institutions consistently outperform counterparts on
      available indices, suggesting that the data elements underlying the rankings may
      provide valid assessments about the quality of care in educational settings.
      CONCLUSIONS: Data elements in the rankings can be used to assess clinical and, to
      a lesser extent, educational quality, but the number of specialties and ranked
      institutions is too small to have a significant effect on widespread clinical or
      educational quality, unless ranked institutions serve as sites for the
      development, study, and dissemination of best practices.

PMID- 19174661
TI  - Academic medicine amenities unit: developing a model to integrate academic
      medical care with luxury hotel services.
AB  - The interface between established values of academic medicine and the trend
      toward inpatient amenities units requires close examination. Opinions of such
      units can be polarized, reflecting traditional reservations about the ethical
      dilemma of offering exclusive services only to an elite patient group. An
      amenities unit was developed at the University of Pennsylvania Health System in
      2007, using an approach that integrated academic medicine values with the
      benefits of philanthropy and service excellence to make amenities unit services
      available to all patients. Given inherent internal political concerns, a broadly
      based steering committee of academic and hospital leadership was developed. An
      academically appropriate model was conceived, anchored by four principles: (1)
      integration of academic values, (2) interdisciplinary senior leadership, (3)
      service excellence, and (4) recalibrated occupancy expectations based on multiple
      revenue streams. Foremost is ensuring the same health care is afforded all
      patients throughout the hospital, thereby overcoming ethical challenges and
      optimizing teaching experiences. Service excellence frames the service ethic for
      all staff, and this, in addition to luxury hotel-style amenities, differentiates
      the style and feel of the unit from others in the hospital. Recalibrated
      occupancy creates program viability given revenue streams redefined to encompass
      gifts and patient revenue, including both reimbursement and self-pay. The medical
      surgical amenities patient-care unit has enjoyed a successful first year and a
      growing stream of returning patients and admitting physicians. Implications for
      other academic medical centers include opportunities to extrapolate service
      excellence throughout the hospital and to cultivate philanthropy to benefit
      services throughout the medical center.

PMID- 19174662
TI  - Call it what it is: sexual harassment.

PMID- 19174663
TI  - Medical humanities and their discontents: definitions, critiques, and
      implications.
AB  - The humanities offer great potential for enhancing professional and humanistic
      development in medical education. Yet, although many students report benefit from
      exposure to the humanities in their medical education, they also offer consistent
      complaints and skepticism. The authors offer a pedagogical definition of the
      medical humanities, linking it to medicine as a practice profession. They then
      explore three student critiques of medical humanities curricula: (1) the content
      critique, examining issues of perceived relevance and intellectual bait-and
      switch, (2) the teaching critique, which examines instructor trustworthiness and
      perceived personal intrusiveness, and (3) the structural/placement critique, or
      how and when medical humanities appear in the curriculum. Next, ways are
      suggested to tailor medical humanities to better acknowledge and reframe the
      needs of medical students. These include ongoing cross-disciplinary reflective
      practices in which intellectual tools of the humanities are incorporated into
      educational activities to help students examine and, at times, contest the
      process, values, and goals of medical practice. This systematic, pervasive
      reflection will organically lead to meaningful contributions from the medical
      humanities in three specific areas of great interest to medical educators:
      professionalism, "narrativity," and educational competencies. Regarding pedagogy,
      the implications of this approach are an integrated required curriculum and
      innovative concepts such as "applied humanities scholars." In turn, systematic
      integration of humanities perspectives and ways of thinking into clinical
      training will usefully expand the range of metaphors and narratives available to
      reflect on medical practice and offer possibilities for deepening and
      strengthening professional education.

PMID- 19174664
TI  - Hana no hana: artist's statement.

PMID- 19174665
TI  - Monitoring and improving resident work environment across affiliated hospitals: a
      call for a national resident survey.
AB  - PURPOSE: To assess, monitor, and improve resident work environment and enhance
      compliance with Accreditation Council for Graduate Medical Education (ACGME)
      institutional requirements among the five Loma Linda University-affiliated
      hospitals using an annual survey. METHOD: From 2001 to 2005, residents completed
      an anonymous questionnaire assessing each hospital's educational and work
      environment regarding clinical services, attending physicians, learning
      opportunities, resident environment, and coordination of care. Resident
      perceptions were compared across hospitals and residency programs. RESULTS: A
      total of 2,399 resident surveys were collected during a five-year period from 500
      residents in 43 different residency programs. The overall response rate was 88%.
      Residents perceived deficiencies in clinical services at the Veterans Affairs
      (VA) hospital. After focused improvement efforts directed to VA clinical
      services, serial data showed significant improvements in residents' perceptions
      of nursing, phlebotomy, radiology, social work, case management, and overall
      clinical services in subsequent years (P < .001). The survey data identified
      resident concerns at other affiliated hospitals and were instrumental in
      persuading hospital administrators to improve the university hospital resident
      lounge and computerized lab results at a county hospital. Resident perceptions
      improved in subsequent years after the changes were made (P < .001). The survey
      also suggested improvements in residency-specific program educational issues.
      CONCLUSIONS: A survey across five consecutive years involving five affiliated
      hospitals provided local benchmarks and serial data to monitor and significantly
      improve resident perceptions of their work environment and ensured optimal
      compliance with ACGME institutional requirements. These results and the data of
      others support the idea of an expanded, national resident survey.

PMID- 19174667
TI  - A novel housestaff educational model for quaternary-care patients at an academic
      health center.
AB  - PURPOSE: Work hour restrictions, external pressure to reduce hospitalization
      costs, and rising inpatient acuity have prompted a variety of changes in the ward
      based educational models traditionally employed in residency training. The impact
      of these changes remains largely unstudied. METHOD: The authors collected data
      retrospectively on hospital patients with advanced liver disease before (July 1,
      2003, to May 31, 2004) and after (July 1, 2004, to May 31, 2005) implementation
      of a novel specialized housestaff service (SHS) model for those patients,
      supervised by a multidisciplinary hepatology team led by an attending
      hepatologist. The authors also assessed the satisfaction of the 118 internal
      medicine residents who had rotated through both the SHS model and a traditional
      housestaff service (THS) in cardiology. RESULTS: In univariate analysis, there
      was a trend toward a reduction in mean length of stay (LOS) after implementation
      of the liver service that did not meet statistical significance (P = .1). After
      adjustment for patient acuity and Model-for-End-Stage-Liver-Disease score,
      implementation of the liver service was associated with a statistically
      significant reduction in LOS (P = .05). In contrast, during the study period,
      there was an increase in LOS on a comparable, nonspecialized medicine housestaff
      ward even after adjustment for patient acuity (P < .01). With respect to
      housestaff satisfaction, 90% of housestaff reported being satisfied overall with
      their experience caring for patients under the SHS model, with a mean score of
      4.1 on a 5-point scale. CONCLUSION: The implementation of the SHS model of
      patient care is associated with a decreased LOS and increased trainee
      satisfaction when compared with the THS model of patient care.

PMID- 19174668
TI  - A metric to evaluate the comparative performance of an institution's graduate
      medical education program.
AB  - The economics of medicine have drastically changed during the past quarter
      century. Institutions may be faced with difficult decisions concerning graduate
      medical education (GME), particularly as it relates to the growth of existing
      programs and the creation of new programs. The authors describe a tool that they
      developed that can consistently measure the value of individual training programs
      while aligning with an institution's strategic priorities. This tool, the
      assessment metric scorecard, permits the annual prioritization of GME programs by
      the leadership of Mayo Clinic, Jacksonville, Florida. The scorecard also provides
      valuable data regarding the strengths and weaknesses of individual programs. The
      metric seeks to evaluate GME programs on the basis of four broad areas: Research,
      Teaching, Patient Service, and a General category. The assessment metric
      scorecard has been used since 2004; this article reports on its use for the
      academic years 2004-2005 and 2005-2006. The scorecard has proved to be a helpful
      tool for the yearly evaluation and prioritization of GME programs at the authors'
      institution. The overall mean score of the GME programs increased, which suggests
      a positive trend. This scorecard is flexible; modifications of the relative
      weights of the metrics can be made to align it with the strategic priorities of
      other institutions. The resources necessary to implement the scorecard are
      minimal.

PMID- 19174669
TI  - The effect of nonteaching services on the distribution of inpatient cases for
      internal medicine residents.
AB  - PURPOSE: Nonteaching services (NTSs) are becoming increasingly prevalent in
      academic hospitals. This study was designed to determine whether the presence of
      an NTS is associated with higher acuity and altered case mix on the teaching
      service. METHOD: The authors carried out a retrospective, cross-sectional
      analysis of data about all general medical admissions between January 1, 2005 and
      June 30, 2005 to either of two teaching hospitals in Rochester, New York. A total
      of 6,907 inpatients were studied, of whom 1,976 (29%) were admitted to medicine
      resident services and 4,931 (71%) were admitted to NTSs. Hospital billing
      databases were used to determine patient demographics, ICD-9 diagnoses, Charlson
      Comorbidity Index scores, and patient disposition. RESULTS: Compared with NTS
      patients, patients on resident services had higher median Charlson Comorbidity
      Index scores (3.0 versus 2.0, P < .001) and numbers of comorbidities (9.0 versus
      8.0, P < .001) and were more likely to require intensive care (15.5% versus 7.6%,
      P < .001) and to die in the hospital (8.2% versus 4.5%, P < .001). Patients on
      the resident services were more likely to have acute renal failure, respiratory
      failure, septicemia, and HIV. Residents were less likely to care for patients
      with primary diagnoses of chest pain, cellulitis, alcohol withdrawal, and sickle
      cell crisis. The differences in patients' conditions between resident services
      and NTSs were similar in the two hospitals and also among patients who had not
      received intensive care. CONCLUSIONS: Patients on resident services may be more
      medically complex and more likely to have high-acuity diagnoses than patients on
      NTSs. How these differences affect residents' education, residents' career
      decisions, and practice styles deserves further study.

PMID- 19174670
TI  - Medicine and the arts. Help by Logan Schneider. Commentary.

PMID- 19174673
TI  - Finding the line: physicians, pharma, and drug development.

PMID- 19174675
TI  - Mightier than the sword?

PMID- 19174676
TI  - A closer look at the implications of information bias.

PMID- 19174677
TI  - Price check! An analysis of direct-to-consumer pharmaceutical marketing.

PMID- 19174678
TI  - Depressive symptoms in medical students and residents: a multischool study.
AB  - BACKGROUND: This multisite, anonymous study assessed depressive symptoms and
      suicidal ideation in medical trainees (medical students and residents). METHOD:
      In 2003-2004, the authors surveyed medical trainees at six sites. Surveys
      included content from the Center for Epidemiologic Studies-Depression scale (CES
      D) and the Primary Care Evaluation of Mental Disorders (PRIME-MD) (measures for
      depression), as well as demographic content. Rates of reported major and minor
      depression and of suicidal ideation were calculated. Responses were compared by
      level of training, gender, and ethnicity. RESULTS: More than 2,000 medical
      students and residents responded, for an overall response rate of 89%. Based on
      categorical levels from the CES-D, 12% had probable major depression and 9.2% had
      probable mild/moderate depression. There were significant differences in
      depression by trainee level, with a higher rate among medical students; and
      gender, with higher rates among women (chi2 = 10.42, df = 2, and P = .005 and
      chi2 = 22.1, df = 2, and P < .001, respectively). Nearly 6% reported suicidal
      ideation, with differences by trainee level, with a higher rate among medical
      students; and ethnicity, with the highest rate among black/African American
      respondents and the lowest among Caucasian respondents (chi2 = 5.19, df = 1, and
      P = .023 and chi2 = 10.42, df = 3, and P = .015, respectively). CONCLUSIONS:
      Depression remains a significant issue for medical trainees. This study
      highlights the importance of ongoing mental health assessment, treatment, and
      education for medical trainees.

PMID- 19174679
TI  - Delaying care, avoiding stigma: residents' attitudes toward obtaining personal
      health care.
AB  - PURPOSE: The authors sought to understand the health issues and care-seeking
      practices reported by residents and explored the extent to which fear of academic
      jeopardy, stigma, and being the subject of discussion by colleagues may affect
      residents' care-seeking. METHOD: Residents at the University of New Mexico Health
      Sciences Center were surveyed in 2000-2001 regarding avoidance or postponement of
      obtaining necessary health care, responses of others to absences, and perceptions
      of jeopardy to training status if a supervisor learned of a specific condition.
      Responses were analyzed via repeated-measures MANOVA. RESULTS: Of 217 surveys,
      155 were returned (71% response rate). Concerns with mental health, pain, minor
      infections, or relationship, sleep-related, fatigue, or gynecological/urological
      problems were expressed by 26% to 43% of residents. Concerns of potential
      jeopardy if a director or supervisor learned about personal health issues were
      strongest for problems with drugs/alcohol, moderately high for HIV, and moderate
      for mental health, eating-related problems, cancer, and STDs. Residents had
      sometimes avoided seeking care, and 18% had often avoided or delayed care
      seeking; women delayed or avoided care more often than men. More frequent
      avoidance of seeking care was associated with poorer self-rated mental and
      physical health and greater health concerns. CONCLUSIONS: Residents at times
      postpone or avoid seeking care. Time and scheduling difficulties influence the
      ability to obtain care. Perceptions of potential academic jeopardy, stigma, and
      reactions of colleagues may affect residents' attitudes and care-seeking. Further
      inquiry is essential to understand how extensively these factors may influence
      the well-being of residents.

PMID- 19174680
TI  - Intern to attending: assessing stress among physicians.
AB  - PURPOSE: Organizations have raised concerns regarding stress in the medical work
      environment and effects on health care worker performance. This study's objective
      was to assess workplace stress among interns, residents, and attending physicians
      using Ecological Momentary Assessment technology, the gold-standard method for
      real-time measurement of psychological characteristics. METHOD: The authors
      deployed handheld computers with customized software to 185 physicians on the
      medicine and pediatric wards of four major teaching hospitals. The physicians
      contemporaneously recorded multiple dimensions of physician work (e.g., type of
      call day), emotional stress (e.g., worry, stress, fatigue), and perceived
      workload (e.g., patient volume). The authors performed descriptive statistics and
      t test and linear regression analyses. RESULTS: Participants completed 5,673
      prompts during an 18-month period from 2004 to 2005. Parameters associated with
      higher emotional stress in linear regression models included male gender (t = 
      2.5, P = .01), total patient load (t = 4.2, P < .001), and sleep quality (t = 
      2.8, P = .006). Stress levels reported by attendings (t = -3.3, P = .001) were
      lower than levels reported by residents (t = -2.6, P = .009), and emotional
      stress levels of attendings and residents were both lower compared with interns.
      CONCLUSIONS: On inpatient wards, after recent resident duty hours changes,
      physician trainees continue to show wide-ranging evidence of workplace stress and
      poor sleep quality. This is among the first studies of medical workplace stress
      in real time. These results can help residency programs target education in
      stress and sleep and readdress workload distribution by training level. Further
      research is needed to clarify behavioral factors underlying variability in
      housestaff stress responses.

PMID- 19174682
TI  - Resilience in the third year of medical school: a prospective study of the
      associations between stressful events occurring during clinical rotations and
      student well-being.
AB  - PURPOSE: In the third year of medical school students are exposed to many
      stressful and potentially traumatic events, including witnessing patient
      suffering or death, personal mistreatment, and poor role modeling by physicians.
      These experiences may explain increases in anxiety and depression during medical
      school. However, to date this has not been studied. METHOD: The present study
      prospectively measured stressful clerkship events occurring during the 2006-2007
      academic year in third-year medical students of the Mount Sinai School of
      Medicine (n = 125), using surveys completed monthly. Students labeled stressful
      events traumatic if they met the trauma criteria of the Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition. The authors measured
      anxiety, depression, and posttraumatic stress symptoms at the beginning and end
      of the year and twice during the year. At year's end they also measured students'
      personal growth. RESULTS: Class participation varied from 106 (85%) at baseline
      to 82 (66%) at endpoint. Most students (101; 81%) completed at least one monthly
      survey. Many students reported exposure to trauma as well as personal
      mistreatment and poor role modeling by superiors. Trauma exposure was positively
      associated with personal growth at year's end. In contrast, exposure to other
      stressful events was positively associated with endpoint levels of depression and
      other stress symptoms. CONCLUSIONS: Trauma exposure was common but not associated
      with poor outcomes by year's end, which suggests that students were resilient.
      Nonetheless, unprofessional behavior by resident and attending physicians might
      have adverse effects on the well-being of students.

PMID- 19174683
TI  - Rationing empathy.

PMID- 19174684
TI  - An exploratory study of resident burnout and wellness.
AB  - PURPOSE: Physicians have a higher rate of burnout compared with the general
      population, and burnout's origin can be traced to residency training. Little
      evidence exists documenting the causes of burnout, and there is even less
      evidence on protective factors. The goal of this exploratory study was to
      determine which resident-identified stressors are associated with the presence of
      burnout and which resident-identified wellness factors are associated with the
      absence of burnout. METHOD: In the fall of 2006, residents from 13 specialties
      completed a demographics questionnaire, a survey of factors that promote burnout
      and wellness, and the Maslach Burnout Inventory. RESULTS: From a pool of 395
      residents, 150 (38%) completed the questionnaires. Of 32 burnout factors, 27 were
      significantly associated with at least one burnout scale. Pessimism was the only
      burnout factor associated with all three burnout scales; 11 other burnout factors
      were associated with at least two burnout scales. Of 29 wellness factors, 25 were
      significantly associated with at least one burnout scale, indicating a lack of
      burnout. Use of prescription medications was the only wellness factor associated
      with all three burnout scales, indicating low burnout. Thirteen other wellness
      factors were associated with at least two of the scales. CONCLUSIONS:
      Significantly more research is needed to further define and measure wellness.
      Program directors should consider multiple burnout and wellness factors
      associated with burnout (or its absence) when designing treatment interventions.
      The aim should be to identify and bolster wellness factors that protect from
      burnout while minimizing the stressors that cause it.

PMID- 19174685
TI  - The pornographic anatomy book? The curious tale of the Anatomical Basis of
      Medical Practice.
AB  - Studying the history of medical education helps teach us that medicine is a
      social activity that occurs in the context of social mores and customs. In 1971,
      a major new anatomy textbook aimed at first-year medical students was published.
      The Anatomical Basis of Medical Practice, written by Professors R. Frederick
      Becker, James S. W. Wilson, and John A. Gehweiler, emphasized surface anatomy,
      embryology, and radiographic anatomy. At multiple places in the text, the authors
      used sexually suggestive and "cheeky" comments about women. A small fraction of
      the illustrations were stylized, posed female nude photographs purchased from
      California photographer Peter Gowland. These photographs, of a type typically
      seen in Playboy centerfolds or "pin-up girl" calendars, produced a firestorm of
      controversy. The book was criticized in the press and in reviews in scholarly
      journals, and a boycott was organized by the Association of Women in Science. The
      publisher received negative feedback from consumers, and the book was withdrawn
      from the market. The book is now a minor collector's item. Professors Becker and
      Wilson vigorously responded. They laid blame for the debacle on the publisher and
      also claimed they were the victims of a witch hunt by feminists. The Anatomical
      Basis of Medical Practice appeared as the women's movement became part of the
      American popular consciousness. It was also an era in which the public began to
      grapple with how to define pornography. Professor Becker and his coauthors
      thought that they were writing a witty, engaging, and funny book. Their
      detractors thought the book denigrated women.

PMID- 19174687
TI  - Clostridium difficile infections in children.

PMID- 19174688
TI  - Diagnosis and management of tuberculous meningitis in HIV-infected pediatric
      patients.

PMID- 19174689
TI  - Severe bilateral pyramidal tract involvement in a patient with Parry-Romberg
      syndrome.
AB  - Parry-Romberg syndrome (PRS) is a rare clinical entity of unknown etiology,
      generally characterized by a slow and progressive atrophy that affects 1 side of
      the face. A variety of neurologic abnormalities have been shown to coexist with
      PRS. However, few studies regarding pyramidal tract involvement in this disorder
      have been reported. We report a unique case, in which the patient presented with
      bilateral pyramidal tract insult and an unusual sequence of disease onset and
      progression. This case suggests a rarer variant of PRS, and the neurologic
      findings indicate that the underlying essential neural degeneration may
      contribute to the processing of pyramidal tract insult or this syndrome.

PMID- 19174690
TI  - A case of Salmonella typhi endocarditis in pregnancy.
AB  - Infective endocarditis (IE) is an uncommon but life-threatening infection during
      pregnancy. Although there have been several reports of endocarditis caused by
      Salmonella typhi, to our knowledge it has not been reported as a cause of
      endocarditis during pregnancy. We report a case of 27-year-old pregnant woman
      with aortic valve IE caused by S. typhi, who had moderate mitral stenosis and
      aortic regurgitation. During pregnancy, fever, increase in sedimentation should
      always alert the physician about the possibility of IE, especially in the
      presence of predisposing clinical conditions. Whenever possible, transesophageal
      echocardiographic evaluation should be performed because transthoracic
      echocardiography might not always demonstrate vegetation as in the present case.

PMID- 19174691
TI  - Endoscopic pyloric injection of botulinum toxin-A for the treatment of
      postvagotomy gastroparesis.
AB  - OBJECTIVES: To evaluate the efficacy of botulinum toxin-A in the treatment of
      postvagotomy gastroparesis. METHODS: This open-labeled trial identified and
      recruited 11 subjects who developed symptomatic gastroparesis after a vagotomy (9
      fundoplication, 1 trauma, and 1 exploratory laparotomy). Gastroparesis was
      defined as an abnormal solid-phase gastric emptying test using the standardized 4
      hour radionuclide eggbeater meal method and vagotomy was confirmed with a sham
      meal challenge test. To complete the study, subjects should have completed the 6
      month follow-up visit after their pylorus was injected with botulinum toxin-A
      injection in a 4-quadrant manner. Patients either received 100 (n = 2) or 200 (n
      = 9) units of botulinum toxin. Questionnaires recorded symptom severity of
      gastroparesis at baseline and at monthly intervals for 6 months after the therapy
      was completed by the patients. RESULTS: Of the 11 subjects initially recruited,
      10 finished the 6-month follow-up visit (7 women). Mean age was 51 years (range,
      31-84 years). Mean symptom score at baseline was 16 (95% CI 13-19) and showed a
      numerical decline to 9 (P > 0.05) over the 6-month period after the procedure
      (95% CI 5-13). Seven (70%) patients observed >30% improvement in the total
      symptom score. No complications were recorded. CONCLUSIONS: In conclusion, this
      open-label study in patients with postvagotomy gastroparesis patients reveals a
      reduction of gastroparetic symptoms at 1 and 3 months after treatment with
      pyloric injection of botulinum toxin-A, with return of symptoms by 6 months.
      Thus, botulinum toxin treatment does not produce a sustained reduction in
      gastroparetic symptoms in this clinical setting.

PMID- 19174692
TI  - Reduced relative lymphocyte count in african-americans with decompensated heart
      failure.
AB  - BACKGROUND: A reduction in relative lymphocyte count (%L) has been reported in
      whites with heart failure that inversely correlated with jugular venous pressure
      thereby implicating systemic venous hypertension with splanchnic congestion.
      OBJECTIVES: : To study whether a reduced %L (<20%) occurs in African-Americans
      (AA) with heart failure and to address pathophysiologic mechanisms having the
      potential to influence lymphocyte biology and survival, we monitored patients
      with or without systemic venous hypertension, hypoalbuminemia, hypovitaminosis D,
      and secondary hyperparathyroidism. METHODS: In 131 AA (90 men; 53 +/- 12 years):
      113 were hospitalized, 50 with decompensated biventricular failure (DecompHF), 24
      with acute left heart failure, and 39 with heart disease, but no heart failure
      (HDNHF); and 18 were outpatients with compensated heart failure. At the time of
      admission or outpatient visit, we monitored: white blood cell count and %L; and
      serum albumin, 25(OH)D, and parathyroid hormone (PTH). RESULTS: White blood cell
      count did not differ among the groups, whereas %L was reduced only in those with
      DecompHF (15 +/- 1%; P < 0.05) versus 25 +/- 2% with left heart failure, 29 +/-
      1% in HDNHF, and 28 +/- 3% in compensated heart failure. Serum albumin was
      reduced in DecompHF (2.8 +/- 0.1; P < 0.05), but not in any of the other groups.
      Reduced 25(OH)D (<30 ng/mL), in keeping with hypovitaminosis D, was found in all
      AA, whereas elevated serum PTH (>65 pg/mL) was found only in those with DecompHF
      (123 +/- 22 pg/mL). CONCLUSIONS: A relative lymphocytopenia, together with
      hypoalbuminemia and elevated PTH, were found only in hospitalized AA with
      DecompHF. These findings implicate splanchnic congestion and the enteric loss of
      lymphocytes and albumin with an associated secondary hyperparathyroidism.

PMID- 19174693
TI  - The research progress of antitumorous effectiveness of Stichopus japonicus acid
      mucopolysaccharide in north of China.
AB  - The sea cucumbers growing in the estuary of the Pohai of northern China are
      called Stichopus japonicus and are the orthodox holothurians in traditional
      Chinese medicine. There are multiple biological active ingredients in S.
      japonicus, and S. japonicus acid mucopolysaccharide (SJAMP) is one of the
      important ingredients. SJAMP has multiple pharmacologic actions, such as
      antitumor, immunologic regulation, anticoagulated blood, and antivirus. The
      research on antitumor has been carried out by way of animal experiments aiming at
      studying internal tumor-inhibiting effect of SJAMP, and the route of
      administration is usually peritoneal or intragastric. Additionally, sea cucumbers
      have been widely recognized and applied as medicated food or therapeutic
      prescriptions during and after the treatment of some tumors.

PMID- 19174694
TI  - Low-dose capecitabine plus docetaxel as first-line therapy for metastatic breast
      cancer: phase II results.
AB  - The addition of capecitabine to docetaxel significantly improves overall survival
      in anthracycline-pretreated metastatic breast cancer. We evaluated a low-dose
      capecitabine-docetaxel regimen as first-line therapy. Patients who had received
      adjuvant anthracyclines received docetaxel 75 mg/m2 on day 1 and capecitabine 950
      mg/m2 twice daily, days 1-14, every 3 weeks until disease progression or
      unacceptable toxicity. The primary endpoint was time to progression. Forty-five
      patients were evaluable (median age 56 years, range 35-75). The response rate was
      42%, including two complete responses. Nine patients (20%) attained stable
      disease. Median time to progression was 8 months and median overall survival was
      23 months. Five patients (11%) experienced grade 3 neutropenia but febrile
      neutropenia was absent. Three patients (7%) experienced grade 3 hand-foot
      syndrome; there was no significant gastrointestinal toxicity. This capecitabine
      docetaxel regimen is an active first-line therapy and appears better tolerated
      than regimens using a higher capecitabine dose. Data from the randomized trial
      comparing the registered versus a lower capecitabine dose, both in combination
      with docetaxel, should definitively answer whether a lower dose provides a better
      safety profile while maintaining the considerable efficacy of this combination.

PMID- 19174695
TI  - Downregulation of survivin and activation of caspase-3 through the PI3K/Akt
      pathway in ursolic acid-induced HepG2 cell apoptosis.
AB  - Ursolic acid (UA), a naturally occurring pentacyclic triterpene, is a potent in
      vitro anticancer agent, acting through control of growth, apoptosis and
      differentiation. As the mechanism of its proapoptotic effects on human
      hepatocellular carcinoma cells has not been extensively studied, we performed an
      in depth evaluation of the effects of UA on apoptosis in human HepG2 cells. UA
      was found to inhibit the proliferation of HepG2 cells in a concentration and time
      dependent manner. After treatment, cells showed evidence of activation of
      apoptosis, including the presence of apoptotic bodies and DNA fragmentation. UA
      induced apoptosis was accompanied by a significant decrease in bcl-2 and survivin
      expression, with the corresponding ratio of bax/bcl-2 increased. The treatment
      with UA also increased the protein level and enzymatic activity of caspase-3. Z
      DEVD-fmk, a specific caspase-3 inhibitor, significantly inhibited both the
      cytotoxic effect and the DNA fragmentation induced by UA, demonstrating the
      requirement for caspase-3 activity in UA-induced apoptosis. Inactivation of the
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway was also involved, as
      inhibition of PI3K by LY294002 significantly increased UA-induced apoptosis.
      Kinetic experiments indicated that UA downregulated PI3K/p85 subunit (PI3K/p85)
      and phospho-Akt, before downregulating survivin. The further results also
      confirmed that LY294002 not only downregulated survivin alone, but considerably
      enhanced the repression of survivin combined with UA. UA therefore seemed to
      downregulate the expression of survivin by blocking PI3K/Akt. Taken together, the
      data suggest that the proapoptotic effect of UA on HepG2 cells is mediated by
      activation of caspase-3, and is highly correlated with inactivation of
      PI3K/Akt/survivin pathway.

PMID- 19174696
TI  - Impact of a compliance program on cholesterol control: results of the randomized
      ORBITAL study in 8108 patients treated with rosuvastatin.
AB  - AIM: To determine whether a compliance-enhancing program could increase the level
      of lipid control in patients treated with rosuvastatin. METHODS AND RESULTS: A
      total of 8108 patients (56% men, mean age 59 years; 44% women, mean age 63 years)
      with low-density lipoprotein cholesterol (LDL-C) >or=115 mg/dl if statin-naive or
      else >or=125 mg/dl were randomized to rosuvastatin 10 mg daily either with or
      without a compliance-enhancing program for 12 months. Patients not achieving the
      goal after 3 months were uptitrated to rosuvastatin 20 mg daily thereafter. At 3,
      6, and 12 months, rosuvastatin plus compliance initiatives were similarly
      effective to rosuvastatin alone in terms of 1998 European LDL-C goal of less than
      115 mg/dl achievement (72 vs. 70%, 71 vs. 69%, 68 vs. 68%) and changes in the
      lipid profile. Significant differences were observed in the subgroup of statin
      naive patients at 3 and 6 months (80 vs. 76% and 78 vs. 73%, P<0.01). The
      frequency of adverse events and relevant changes in laboratory data were
      consistent with the known safety profile of rosuvastatin. CONCLUSION:
      Rosuvastatin 10/20 mg daily enables the majority of patients to achieve LDL-C
      less than 115 mg/dl within 3 months. The compliance-enhancing program was only
      effective in statin-naive patients at early time points, but had no overall
      effect over 12 months.

PMID- 19174697
TI  - Safer sedation practice may not translate into improvements in endoscopic
      outcomes.
AB  - INTRODUCTION: Although the literature surrounding sedation practice and
      endoscopic outcomes remains sparse and controversial, there have been a number of
      stringent guidelines issued regarding sedation use in endoscopy. AIMS: To assess
      the impact of changes to enhance safer sedation practice on endoscopic outcomes.
      METHODS: Sedation practice was audited in 7234 consecutive gastrointestinal
      endoscopic procedures in 2004 and protocols for enhancing safer sedation practice
      were introduced. These included; introduction of a unit sedation policy, exchange
      of midazolam 10 mg vials to 5 mg repacked syringes, adverse events recording of
      midazolam use of greater than 5 mg and reversal agents, more stringent patient
      monitoring procedures and endoscopists education and feedback. A reaudit of 7071
      procedures was performed in 2006. Outcomes audited the included midazolam doses,
      patient intolerance, 30-day postprocedure mortality, reversal agent use and total
      adverse events. RESULTS: Sedation doses were reduced substantially after
      intervention [mean midazolam dose (SD): 4.9 mg (2.5) in 2004 vs. 2.9 mg (1.2) in
      2006; P<0.0001] with no endoscopist using a mean greater than 5 mg in 2006
      compared with 19% in 2004 (P=0.005). The use of reversal agents (0.6 vs. 0.7% for
      2004 and 2006, respectively; P=0.74), mortality (1.0 vs. 1.3%; P=0.23) and the
      adverse events (1.7 vs. 2%; P=0.44) were similar. Unsuccessful procedures because
      of patient intolerance increased from 0.1 to 1.9% (P<0.0001). CONCLUSION:
      Although protocols to enhance safer sedation practice substantially reduced
      sedation doses used; this did not, however, translate into improved endoscopic
      outcomes. Moreover, incomplete procedures because of poor tolerance increased.

PMID- 19174698
TI  - Strategies for innovation and interdisciplinary translational research: research
      and career benefits and barriers.
AB  - Following is a portion of the proceedings of the panel and audience discussion
      from the AFMR-Translational Medical Research Development Workshop at EB08.

PMID- 19174699
TI  - Strategies for innovation and interdisciplinary translational research: removal
      of barriers through the CTSA mechanism.
AB  - The National Institutes of Health's Clinical and Translational Science Award
      program has had a profound impact upon the way research is conducted at the
      University of California, Davis. University of California, Davis was among the
      first cohort of 12 institutions to receive National Institutes of Health funding
      for this award, and created its Clinical and Translational Science Center (CTSC)
      in 2006. The presence of a CTSC has led us to develop new ways of bringing
      together and supporting researchers from diverse fields, and the CTSC has
      impacted on virtually every area and infrastructure resource involved in
      supporting clinical and translational research at our institution.

PMID- 19174700
TI  - Training interdisciplinary scientists for systems biology.
AB  - The rise of interdisciplinary research programs in recent years has spawned
      numerous questions regarding the best way to organize interdisciplinary programs
      and how to best train new interdisciplinary scientists in ways that will catalyze
      novel discoveries in biology. Systems biology, a relatively new branch of
      science, can be considered in many respects a poster child for modern
      interdisciplinary science. It not only requires that people from different
      traditional disciplines work closely together but it also requires the
      development of unique training environments to educate the next generation of
      systems biologists. The unique scientific and training challenges associated with
      the development of systems biology are certainly faced across the spectrum of
      interdisciplinary endeavors. Therefore, it is useful for scientists interested in
      building interdisciplinary research programs to consider the merits of successful
      systems biology initiatives. Institute for Systems Biology is one such example,
      and in the following, several key aspects of Institute for Systems Biology that
      make it both a unique and successful interdisciplinary science and training
      center are discussed.

PMID- 19174701
TI  - What is needed to promote translational research and how do we get it?

PMID- 19174702
TI  - Series on: strategies for innovation and interdisciplinary translational
      research: research and career benefits and barriers.

PMID- 19174703
TI  - Effects of diet and gemfibrozil on posttransplant hyperlipidemia in renal
      transplant recipients.
AB  - BACKGROUND: Posttransplant hyperlipidemia increases cardiovascular morbidity and
      mortality rate in renal transplant recipients. It also leads to graft loss due to
      atherosclerosis and glomerular damage. It is essential to control hyperlipidemia
      in renal transplant recipients to prevent these events. METHODS: In our study, we
      determined lipid profiles in 59 renal transplant recipients. Twenty of the
      recipients had hyperlipidemia; 9 had type IV, and 11 had type II
      hyperlipoproteinemia. Randomly selected 14 of 20 hyperlipidemic patients
      consisted of the diet group and were treated with American phase 3 diet for 1
      month. Randomly selected 6 of the 20 hyperlipidemic patients received their
      regular diet as the control group. Five diet-resistant patients in the American
      phase 3 diet group were given diet plus placebo for another 1 month and then they
      were given diet plus Gemfibrozil (600 mg twice a day) for 2 months. RESULTS:
      Lipid profile was normalized in 9 of the 14 patients on American phase 3 diet.
      The lipid profile of 5 patients in the American phase 3 diet group did not change
      significantly after 1-month diet. These 5 diet-resistant patients were given diet
      plus placebo for another 1 month, and their lipid levels again did not change
      significantly. Afterward, they were treated with Gemfibrozil (600 mg twice a day)
      plus American phase 3 diet for 2 months. At the end of this therapy period, their
      cholesterol level and triglyceride level decreased significantly. No change was
      observed in low-density lipoprotein cholesterol and high-density lipoprotein
      cholesterol levels. CONCLUSIONS: We conclude that American phase 3 diet and/or
      Gemfibrozil are effective in controlling posttransplant hyperlipidemia in renal
      transplant recipients.

PMID- 19174704
TI  - Collaborative care interventions for depression in the elderly: a systematic
      review of randomized controlled trials.
AB  - OBJECTIVE: To determine the effective components and the feasibility of
      collaborative care interventions (CCIs) in the treatment of depression in older
      patients. METHODS: Systematic review of randomized controlled trials, in which
      CCIs were used to manage depression in patients aged 60 or older. RESULTS: We
      identified 3 randomized controlled trials involving 3930 participants, 2757 of
      whom received CCIs and the others received usual care. Collaborative care
      interventions were more effective in improving depression symptoms than usual
      care during each follow-up period. Compared with baseline, thoughts of suicide in
      subjects receiving CCIs significantly decreased (odds Ratio [OR], 0.52; 95%
      confidence intervals [CI], 0.35-0.77), but not that in those receiving usual care
      (OR, 0.85; 95% CI, 0.50-1.43). Subjects receiving CCIs were significantly more
      likely to report depression treatment (including any antidepressant medication
      and psychotherapy) than those receiving usual care during each follow-up period.
      Collaborative care interventions significantly increased depression-free days,
      but did not significantly increase outpatient cost. At 6 and 12 months
      postintervention, compared with those receiving usual care, participants
      receiving CCIs had lower levels of depression symptoms and thoughts of suicide.
      Moreover, participants receiving CCIs were significantly more likely to report
      antidepressant medication treatment, but were not significantly more likely to
      report psychotherapy. Collaborative care interventions with communication between
      primary care providers and mental health providers were no more effective in
      improving depression symptoms than CCIs without such communication. CONCLUSIONS:
      Collaborative care interventions are more effective for depression in older
      people than usual care and are also of high value. Antidepressant medication is a
      definitely effective component of CCIs, but communication between primary care
      providers and mental health providers seems not to be an effective component of
      CCIs. The effect of psychotherapy in CCIs should be further explored.

PMID- 19174707
TI  - Hearing rehabilitation counseling for patients with otosclerosis-related hearing
      loss.
AB  - OBJECTIVE: To standardize preoperative counseling for stapedectomy candidates.
      STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center.
      PATIENTS: Preoperative and postoperative hearing thresholds of 54 patients (55
      stapedectomies) were retrospectively recorded. Patients (age range, 17-67 yr)
      were divided into 3 groups that differed significantly in their mean preoperative
      air conduction (AC) pure-tone averages (PTA) (up to 50, 50-70, and 70-90 dB).
      INTERVENTION: Comparison of the gap between the mean hearing thresholds achieved
      postoperatively and the target threshold (normal hearing) in the 3 groups. MAIN
      OUTCOME MEASURES: Preoperative and postoperative AC thresholds, bone-conduction
      (BC) thresholds, and air-bone gap at 0.5, 1.0, 2.0, and 4.0 Hz. RESULTS: Patients
      in the group with a mean preoperative AC below 50 dB had excellent postoperative
      results and achieved normal hearing thresholds. In the group with a mean
      preoperative AC of 50 to 70 dB, the postoperative results were good, but normal
      hearing thresholds were not achieved. Postoperative results in the third group
      were within the range of moderate hearing loss, allowing these patients to use
      hearing aids much more successfully than preoperatively. In each of the 3 groups,
      mean group differences between the preoperative and the postoperative values of
      AC-PTA thresholds, BC-PTA thresholds, and air-bone gap were statistically
      significant. Comparisons between each pairing of the stratified groups also
      yielded statistically significant differences. CONCLUSION: The preoperative AC
      PTA threshold value can be viewed as a convenient, valid, and standardized basis
      for better informed and more comprehensive counseling of stapedectomy candidates
      with regard to options for hearing rehabilitation.

PMID- 19174708
TI  - The importance of repeated clinical examination in patients with suspected benign
      paroxysmal positional vertigo.
AB  - OBJECTIVE: We enable patients with recurrent vertigo, who were examined during an
      asymptomatic period, to be reexamined on an urgent basis when the symptoms
      reappear. In this study, we tried to establish the usefulness of this
      arrangement. STUDY DESIGN: Retrospective case review. SETTING: Outpatient clinic.
      INTERVENTION: We reviewed the medical records of patients treated at our
      dizziness clinic for benign paroxysmal positional vertigo (BPPV) during 1999
      2008. MAIN OUTCOME MEASURES: The rate and characteristics of patients with BPPV
      where the diagnosis was established on reexamination. RESULTS: : Among 464
      patients treated for BPPV, 364 were seen during asymptomatic period, whereas in
      100 patients (21.5%), the diagnosis was established during reexamination. In 86
      of them, BPPV was suspected during the first visit, and in the remaining
      patients, another diagnosis was initially assumed.The mean period between the
      first visit to final diagnosis was 14.9 months. Seven percent of patients had to
      be examined repeatedly until signs of BPPV could be elicited. Seventy-nine
      percent of patients had a laboratory examination before the diagnosis was
      established. CONCLUSION: At a specialized clinic, the method of reexamination in
      patients with recurrent vertigo and a normal neurotologic examination between
      attacks are useful for clarifying the diagnosis. A high confidence is justified
      when suspecting the diagnosis of BPPV between the attacks. Auxiliary examinations
      can be reserved for cases with an atypical history or abnormal findings on
      neurotologic testing.

PMID- 19174709
TI  - Cone beam computed tomography, a low-dose imaging technique in the postoperative
      assessment of cochlear implantation.
AB  - BACKGROUND: Cone beam computed tomography (CBCT) has become an extremely useful
      technique for dentomaxillofacial imaging because it provides clear images of
      highly contrasted structures. Previous studies evaluating the applicability of
      this technique in otologic imaging were very encouraging but were only performed
      in vitro on temporal bone specimens. The intracochlear positioning of the
      individual electrodes after cochlear implantation by means of CBCT has not yet
      been shown in vivo. OBJECTIVE: We describe a protocol for in vivo postoperative
      imaging of cochlear implants by CBCT. Moreover, the effective dose was measured
      and compared with the effective dose used on 4- and 16-slice multislice computed
      tomography (MSCT) by using a RANDO-phantom. MAIN OUTCOME MEASURE: Developing a
      protocol for in vivo postoperative imaging of cochlear implants by CBCT. RESULTS:
      CBCT provides high-resolution and almost artifact-free multiplanar reconstruction
      images allowing assessment of the precise intracochlear position of the electrode
      and visualization of each of the individual contacts. The calculated effective
      dose of the used CBCT and MSCT acquisitions is 80 musv for the CBCT, 3,600 musv
      for the 16-slice computed tomography, and 4,800 musv for the 4-slice computed
      tomography. CONCLUSION: These preliminary results suggests that, for in vivo
      postoperative evaluation of cochlear implants, CBCT can provide at least the same
      information as conventional radiography, digital radiograph, and MSCT but in a
      more comfortable and a much more safer way.

PMID- 19174710
TI  - Partial ossicular reconstruction: comparison of three different prostheses in
      clinical and experimental studies.
AB  - OBJECTIVE: To compare the reconstruction results of a long incus process defect
      using 3 different partial ossicular replacement prostheses (PORP). STUDY DESIGN:
      Temporal bone experiments and retrospective case review. SETTING: Tertiary
      referral center. EXPERIMENTAL MATERIAL AND PATIENTS: The experimental study was
      performed on 18 temporal bones; 66 patients with retraction pockets, chronic
      otitis media with or without cholesteatoma. INTERVENTIONS: Ossiculoplasty using 3
      different PORP: titanium angle prosthesis, autologous incus interposition, and
      titanium clip prosthesis. MAIN OUTCOME MEASURES: Laser Doppler vibrometry in
      temporal bones measured transmission properties of the PORP. Patients were
      retrospectively assessed up to 5 years after surgery. Audiologic data were
      analyzed for preoperative and postoperative air conduction and air-bone gap at
      0.5, 1, 2, 3, and 4 kHz. Statistical analyses compared the outcome in the
      experimental and clinical setting. RESULTS: Experimentally, the titanium PORP
      showed similar transmission properties because the overall difference to the
      intact specimen was -4.14 +/- 0.59 dB for the titanium angle prosthesis and -4.61
      +/- 0.57 dB for the titanium clip prosthesis. The transmission after an
      autologous incus interposition was significantly worse (-9.32 +/- 0.39 dB, p < or
      = 0.001) compared with the other prostheses. Patients' mean postoperative air
      bone gap was 25.5 +/- 1.2 dB and less than 20 dB in at least 66% of cases without
      any significant differences between the groups. CONCLUSION: In the clinical
      setting, the confounding factors that influence the acoustic outcome after
      partial ossiculoplasty obscure the prosthesis-related transmission factors that
      can otherwise be derived in the experimental setting. The results do not
      generally favor the use of 1 specific prosthesis, rather they suggest that the
      correct choice of a prosthesis be based on the anatomic and pathophysiologic
      conditions found in the individual patient.

PMID- 19174712
TI  - Surgical simulation: why now?

PMID- 19174711
TI  - Failure of gamma-aminobutyrate acid-beta agonist baclofen to improve balance,
      gait, and postural control after vestibular schwannoma resection.
AB  - INTRODUCTION: Incomplete postural control often occurs after vestibular
      schwannoma (VS) surgery. Customized vestibular rehabilitation in man improves and
      speeds up this process. Animal experiments have shown an improved and faster
      vestibular compensation after administration of the gamma-aminobutyrate acid
      (GABA)-beta agonist baclofen. OBJECTIVE: To examine whether medical treatment
      with baclofen provides an improvement of the compensation process after VS
      surgery. DESIGN: A time-series study with historical control. SETTING: Tertiary
      referral center. METHODS: Thirteen patients who underwent VS resection were
      included and compared with a matched group of patients. In addition to an
      individualized vestibular rehabilitation protocol, the study group received
      medical treatment with 30 mg baclofen (a GABA-beta agonist) daily during the
      first 6 weeks after surgery. MAIN OUTCOME MEASURES: Clinical gait and balance
      tests (Romberg maneuver, standing on foam, tandem Romberg, single-leg stance,
      Timed Up & Go test, tandem gait, Dynamic Gait Index) and Dizziness Handicap
      Inventory. Follow-up until 24 weeks after surgery. RESULTS: When examining the
      postoperative test results, the group treated with baclofen did not perform
      better when compared with the matched (historical control) group. Repeated
      measures analysis of variance revealed no significant group effect, but a
      significant time effect for almost all balance tests during the acute recovery
      period was found. An interaction effect between time and intervention was seen
      concerning single-leg stance and Dizziness Handicap Inventory scores for the
      acute recovery period. CONCLUSION: Medical therapy with baclofen did not seem to
      be beneficial in the process of central vestibular compensation.

PMID- 19174713
TI  - Preclinical investigation of the retinal biocompatibility of six novel vital dyes
      for chromovitrectomy.
AB  - PURPOSE: To investigate the retinal biocompatibility of six novel vital dyes for
      chromovitrectomy. METHODS: An amount of 0.05 mL of 0.5% and 0.05% light green
      (LG), fast green (FG), Evans blue (EB), brilliant blue (BriB), bromophenol blue
      (BroB), or indigo carmine (IC) was injected intravitreally in the right eye,
      whereas in the left eye balanced salt solution was applied for control in
      rabbits' eyes. Clinical examination, fluorescein angiography, histology with
      light microscopy, and transmission electron microscopy were performed after 1 and
      7 days. Retinal cell layers were evaluated for morphologic alterations and number
      of cells. The electroretinographic changes were assessed at baseline, 24 hours
      and 7 days. RESULTS: Fluorescein angiography disclosed hypofluorescent spots only
      in the 0.5% EB group. Light microscopy and transmission electron microscopy
      disclosed slight focal morphologic changes in eyes exposed to 0.05% IC, FG, BriB,
      similar to the control at 1 and 7 days. In the lower dose groups, EB, LG, and
      BroB caused substantial retinal alterations by light microscopy. At the higher
      dose, BroB and EB produced diffuse cellular edema and vacuolization within the
      ganglion cells, bipolar cells, and photoreceptors. FG and IC at 0.5% caused
      slight retinal alterations similar to balanced salt solution injection. LG at
      0.5% caused diffuse vacuolization of bipolar cells after 1 and 7 days. Injection
      of 0.5% EB caused a significant decrease in neuroretinal cell counts in
      comparison to control eyes in the 7-day examination (P < 0.05).
      Electroretinography revealed intermittent prolonged latency and decreased
      amplitude in eyes injected with 0.5% EB, LG, BriB, and BroB, while at the lower
      dose, only LG and EB induced few functional changes. CONCLUSION: The progressive
      order of retinal biocompatibility, from safest to most toxic, was IC, FG, BriB,
      BroB, LG, EB.

PMID- 19174715
TI  - Refractive outcomes of phacoemulsification and intraocular lens implantation
      after pars plana vitrectomy.
AB  - PURPOSE: To describe the visual acuity outcomes of patients undergoing
      phacoemulsification and intraocular lens implantation after pars plana
      vitrectomy, and to compare of refractive errors after phacoemulsification and
      intraocular lens implantation in the cases of vitrectomized eyes and
      nonvitrectomized eyes. METHODS: The subjects of this study were 45 eyes performed
      phacoemulsification after vitrectomy from January 2004 to February 2007. Office
      records were reviewed for best-corrected visual acuity before and after
      phacoemulsification. In 45 vitrectomized eyes (Group V) and 50 nonvitrectomized
      eyes (Group P), we compared the predicted refraction by preoperative data, and
      actual postoperative refraction of postoperative 2 months. RESULTS: The average
      interval from pars plana vitrectomy to phacoemulsification was 11.5 months. In
      Group V, 41 of 45 eyes (91.1%) had improved best-corrected visual acuity more
      than one line, after phacoemulsification. Although, more hyperopic shift was
      noted in Group V than Group P, there was no significant difference between the
      predicted refraction by preoperative data and postoperative manifest refraction
      in both groups. CONCLUSION: Phacoemulsification after pars plana vitrectomy
      showed no significant difference between the predicted refraction by preoperative
      data and the actual postoperative refraction.

PMID- 19174714
TI  - Involvement of illumination in indocyanine green toxicity after its washout in
      the ex vivo rat retina.
AB  - PURPOSE: To elucidate the involvement of illumination in indocyanine green (ICG)
      retinal toxicity. METHODS: We incubated isolated rat retinas with or without
      illumination after exposure to 0.5% ICG. We also examined whether a time lag
      following ICG exposure before illumination altered the damage. Toxicity was
      evaluated by histologic and biochemical assays, including measurement of lactate
      dehydrogenase release. RESULTS: Retinas fixed immediately after ICG exposure
      showed minimal morphologic changes. However, illumination for 3 hours at 34
      degrees C starting after washout of ICG selectively damaged the outer nuclear
      layer. Retinas incubated for 3 hours under the same condition in the dark showed
      preserved morphology but were damaged by subsequent illumination. When retinas
      were illuminated after washout of ICG at a lower temperature (30 degrees C), the
      damage was attenuated. Results obtained using lactate dehydrogenase release were
      consistent with these morphologic changes. CONCLUSIONS: Incubating retinas in the
      dark and cooling after ICG exposure significantly inhibited retinal damage,
      suggesting that ICG interacts with illumination to induce retinal damage.

PMID- 19174716
TI  - Retinal pigment epithelial tears in ranibizumab-treated eyes.
AB  - PURPOSE: To report the incidence of retinal pigment epithelial (RPE) tears in
      patients treated with ranibizumab therapy for choroidal neovascularization due to
      age-related macular degeneration. DESIGN: : Interventional case series. METHODS:
      One hundred sixty-four eyes from a large clinical practice were retrospectively
      reviewed for number of injections and the presence or absence of a fibrovascular
      retinal pigment epithelial detachment. Main outcome measures were occurrence of
      RPE tears, and timing of tears following the last injection. RESULTS: Patients
      were observed for an average of 11 months. A single patient (0.61%) experienced
      an RPE tear and this occurred after the first injection. In eyes with a
      fibrovascular retinal pigment epithelial detachment the incidence was 5%. Lesions
      containing a fibrovascular retinal pigment epithelial detachment tended to be
      larger (4.5 versus 3.8 Macular Photocoagulation Study Disc Areas), but this was
      not statistically significant. (P = 0.63). However, these lesions required more
      injections on average (P = 0.05). CONCLUSION: The incidence of RPE tears
      associated with ranibizumab therapy is low and may result from a predisposition
      rather than an effect of treatment. Even so, patients undergoing ranibizumab
      therapy should be counseled regarding this possible complication.

PMID- 19174717
TI  - Bevacizumab compared with macular laser grid photocoagulation for cystoid macular
      edema in branch retinal vein occlusion.
AB  - INTRODUCTION: To evaluate the outcome of cystoid macular edema treated with
      intravitreal injections of bevacizumab and macular grid laser photocoagulation
      (GLP), in patients with perfused branch retinal vein occlusion. METHODS: Thirty
      eyes of 30 consecutive patients with cystoid macular edema secondary to
      nonischemic branch retinal vein occlusion were assigned to either GLP group or to
      intravitreal bevacizumab (IB) group. Complete ophthalmologic examinations were
      performed just before GLP and IB injection at 1, 3, 6, and 12 months after
      treatment. Changes in logarithm of minimum angle of resolution (logMAR) best
      corrected visual acuity (BCVA), central macular thickness (CMT) shown by optical
      coherence tomography-3 were evaluated. RESULTS: Baseline BCVA (logMAR) and CMT
      were, respectively, 0.89 +/- 0.13 and 650 +/- 140 microm for the GLP group, 0.87
      +/- 0.16 and 690 +/- 120 microm for the IB group. After the treatment, at 1, 3,
      6, and 12 months in the GLP group, BCVA had improved by 0.19, 0.22, 0.21, and
      0.20 logMAR, CMT had decreased by 40%, 41.3%, 40.5%, and 42%. In the IB group,
      BCVA had improved by 0.31, 0.32, 0.30, and 0.31 logMAR and CMT had decreased by
      59.5%, 59%, 60%, and 60.3%. The group receiving bevacizumab had better BCVA and
      lower CMT values at all time points (P < 0.05). CONCLUSION: Intravitreal
      bevacizumab injection improves BCVA and reduces CMT more than GLP. Intravitreal
      bevacizumab injection was well tolerated and could be used as primary treatment
      in patients with cystoid macular edema secondary to perfused branch retinal vein
      occlusion.

PMID- 19174718
TI  - Acute-onset endophthalmitis after cataract surgery: success of initial therapy,
      visual outcomes, and related factors.
AB  - PURPOSE: To evaluate the success of initial treatment and the factors influencing
      the outcome in acute-onset endophthalmitis after cataract surgery. METHODS: We
      retrospectively reviewed the medical records of all patients with acute
      postoperative endophthalmitis between 2000 and 2007. We performed pars plana
      vitrectomy (PPV) to all eyes with initial visual acuity of light perception. Eyes
      with visual acuity of hand motions or better underwent either intraocular
      antibiotic injection (IOAI) or PPV. Eyes that did not give a good clinical
      response to initial therapy within 60 hours underwent a second procedure. The
      main outcome measure was the rate of early reintervention after PPV and IOAI.
      RESULTS: We evaluated 88 eyes of 88 patients. Thirty-seven patients underwent PPV
      and 51 patients underwent IOAI alone. Six of 37 (16.2%) patients required 1 or
      more procedures within 60 hours of the initial procedure in the PPV group. Twenty
      eight of 51 eyes (54.9%) in the IOAI group underwent PPV within 60 hours. The
      rate of response to primary PPV was significantly higher than to primary IOAI (P
      < 0.001). Gram-negative organisms composed 35.1% of the isolates. CONCLUSION:
      Pars plana vitrectomy may be preferable to IOAI in postoperative endophthalmitis
      since the rate of early reintervention is lower with initial PPV.

PMID- 19174719
TI  - Association of the extent of diabetic macular edema as assessed by optical
      coherence tomography with visual acuity and retinal outcome variables.
AB  - PURPOSE: To determine whether the extensiveness of diabetic macular edema using a
      10-step scale based on optical coherence tomography explains pretreatment
      variation in visual acuity and predicts change in macular thickness or visual
      acuity after laser photocoagulation. METHODS: Three hundred twenty-three eyes
      from a randomized clinical trial of two methods of laser photocoagulation for
      diabetic macular edema were studied. Baseline number of thickened optical
      coherence tomography subfields was used to characterize diabetic macular edema on
      a 10-step scale from 0 to 9. Associations were explored between baseline number
      of thickened subfields and baseline fundus photographic variables, visual acuity,
      central subfield mean thickness (CSMT), and total macular volume. Associations
      were also examined between baseline number of thickened subfields and changes in
      visual acuity, CSMT, and total macular volume at 3.5 and 12 months after laser
      photocoagulation. RESULTS: For baseline visual acuity, the number of thickened
      subfields explained no more variation than did CSMT, age and fluorescein leakage.
      A greater number of thickened subfields was associated with a greater baseline
      CSMT, total macular volume, area of retinal thickening, and degree of thickening
      at the center of the macula (r = 0.64, 0.77, 0.61-0.63, and 0.45, respectively)
      and with a lower baseline visual acuity (r = 0.38). Baseline number of thickened
      subfields showed no association with change in visual acuity (r < or = 0.01-0.08)
      and weak associations with change in CSMT and total macular volume (r from 0.11
      to 0.35). CONCLUSION: This optical coherence tomography based assessment of the
      extensiveness of diabetic macular edema did not explain additional variation in
      baseline visual acuity above that explained by other known important variables
      nor predict changes in macular thickness or visual acuity after laser
      photocoagulation.

PMID- 19174720
TI  - Effects of perfluorocarbon liquids and silicone oil on human retinal pigment
      epithelial cells and retinal ganglion cells.
AB  - PURPOSE: To examine the effects of perfluorocarbon liquid (PFCL) and silicone oil
      (SO) on human retinal pigment epithelium (RPE) cells and retinal ganglion cells
      (RGCs) in vitro. METHODS: Human RPE cells (ARPE-19 cells), seeded on microporous
      inserts, were exposed to PFCL or SO and incubated for 3 or 7 days.
      Perfluorocarbon liquid was in contact with cells at the apical or baso-lateral
      side, not inhibiting cell feeding. Then, the quantification of cell proliferation
      and cell viability were evaluated by WST-1 assay. In the same way, RGCs were
      exposed for 1 hour or 3 days, and the number of viable RGCs was counted by using
      a fluorescence viability agent. RESULTS: Perfluorocarbon liquid affected the
      survival of ARPE-19 cells and RGCs when compared with the nontreated control
      group. ARPE-19 cells decreased significantly after being in contact with PFCL at
      the baso-lateral side for 7 days. However, PFCL contact at the apical side
      reduced the number of RGCs in a time-dependent manner. In case of SO, the
      viability of the ARPE-19 cells decreased significantly after being in contact
      with SO at the baso-lateral side for 7 days. However, SO did not reduce the
      number of RGCs after a 3-day exposure. CONCLUSION: Perfluorocarbon liquid is
      directly toxic to ARPE-19 cells when exposed to the cells for 7 days. On the
      contrary, it seems that RGCs are damaged in a time-dependent manner by the more
      mechanical rather than toxic effects of PFCL. Silicone oil seems to exert
      mechanical rather than toxic effects on ARPE-19 cells. When PFCL is used as a
      postoperative tamponade clinically, understanding the difference in the effects
      will lead to more effective and safer results.

PMID- 19174721
TI  - Treatment of primary intraocular lymphoma (PIOL) has involved systemic,
      intravitreal or intrathecal chemotherapy and/or radiotherapy.

PMID- 19174722
TI  - Vital dyes for macular surgery: a comparative electron microscopy study of the
      internal limiting membrane.
AB  - PURPOSE: To analyze and compare the ultrastructure of the retinal cleavage plane
      of the internal limiting membrane (ILM) removed during dye-assisted macular
      surgery. METHODS: Ninety-six surgical specimens of the ILM obtained during trypan
      blue (TB)-, brilliant blue G (BBG)-, bromphenol blue (BPB)-, Chicago blue (CB)-,
      and indocyanine green-assisted pars plana vitrectomy for idiopathic macular hole
      and macular pucker were evaluated using transmission electron microscopy.
      Specimens removed without dye assistance served as controls. RESULTS: Specimens
      removed after TB-, BBG-, BPB-, and CB-staining presented with significantly less
      cellular fragments (in size and quantity) at the retinal side of the ILM than
      specimens after indocyanine green staining. Large cellular fragments and Muller
      cell endfeet, which were typically present after indocyanine green staining, were
      not found after TB, BBG, BPB, and CB staining. Comparing all groups, TB was found
      with less retinal debris than BBG, BPB, and CB. Specimens removed without
      intravitreal dye administration showed the least retinal fragments that were
      solitarily distributed at the ILM. CONCLUSION: Trypan blue, BBG, BPB, and CB
      cause significantly less morphologic changes at the retinal cleavage plane than
      indocyanine green. Further studies are required to elucidate if presence and
      amount of retinal cell fragments at ILM specimens correlate with functional
      deficits.

PMID- 19174723
TI  - 25-Gauge sutureless vitrectomy versus 20-gauge vitrectomy for the repair of
      primary rhegmatogenous retinal detachment.
AB  - PURPOSE: To compare the anatomic and visual results and complications of 25-gauge
      transconjunctival sutureless vitrectomy versus conventional 20-gauge vitrectomy
      for the management of primary rhegmatogenous retinal detachment. METHODS: A
      retrospective comparative analysis of 125 consecutive eyes from 125 patients with
      a minimum of 3 months follow-up was performed. All patients underwent primary
      vitrectomy with complete fluid air exchange, gas tamponade, and laser retinopexy.
      Excluded were eyes with prior retinal or vitreous surgery, and patients with
      inadequate follow-up. Sixty-four patients underwent 25-gauge transconjunctival
      sutureless vitrectomy and 61 patients underwent 20-gauge pars plana vitrectomy
      from September 2004 to April 2007. Primary endpoints included one surgery retinal
      reattachment success rate, visual outcomes, postoperative intraocular pressures
      and complications as determined by standard clinical evaluation. RESULTS:
      Baseline demographic and preoperative ocular characteristics showed no
      statistically significant difference between the two cohorts. The mean follow-up
      interval was 305.4 days for the 25-gauge group and 452.4 days for the 20-gauge
      group. The single operation success rate with one procedure was 58/64 (90.6%) for
      25-gauge cases and 56/61 (91.8%) for 20-gauge cases, Fisher Exact Test (P =
      0.801). All cases were attached at final follow-up and the anatomic success rate
      was 100% for each of the two cohorts. Preoperative best-corrected visual acuity
      (BCVA) was 20/125 and 20/169 for 25-gauge and 20-gauge cases, respectively (P >
      0.5). The final follow-up mean BCVA was 20/34 and 20/36 for the 25-gauge and 20
      gauge groups, respectively (P > 0.6). In the 25-gauge group two cases were
      complicated by hypotony that resolved uneventfully and one case developed
      postoperative choroidal and vitreous hemorrhage. In the 20-gauge group there was
      one case of sterile endophthalmitis and one case of vitreous hemorrhage.
      CONCLUSION: There was no significant difference between 25-gauge
      transconjunctival sutureless vitrectomy and 20-gauge vitrectomy for the repair of
      primary rhegmatogenous retinal detachments.

PMID- 19174724
TI  - Suprachoroidal hemorrhage during pars plana vitrectomy in traumatized eyes.
AB  - BACKGROUND: Suprachoroidal hemorrhage (SCH) is a rare but dangerous complication
      of intraocular surgery. There are some risk factors for this devastating
      complication during pars plana vitrectomy. In this case, we will report the
      intraoperative occurrence of SCH during pars plana vitrectomy in traumatized
      eyes. METHODS: Retrospective analysis of SCH during pars plana vitrectomy in five
      eyes with the history of blunt (n = 1) or penetrating (n = 4) trauma was made.
      Baseline systemic and ocular characteristics, surgical procedures, time point of
      SCH, management of SCH, and final visual outcomes were measured. RESULTS: One eye
      with associated myopia developed SCH during the time of producing vitreous
      posterior detachment under ocular hypotony. In other two eyes, SCH developed
      under ocular hypotony during fluid-gas exchange. The remaining two eyes got SCH
      when the depression of the area of pars plana occurred. Sclerotomy closure was
      performed immediately once SCH occurred. Vitrectomy and posterior sclerotomy were
      then performed between 8 and 12 days later. After a median follow-up of 12 months
      (range: 3-20 months), final visual acuity was above 20/400 in four eyes, no light
      perception in one eye, the best visual acuity was 20/60. CONCLUSIONS: Ocular
      trauma is one of the vital risk factors for the development of intraoperative SCH
      during pars plana vitrectomy. It is important to control effectively the
      intraocular inflammation preoperatively and avoid abrupt ocular hypotony and
      pressure on the area of pars plana intraoperatively to the limit.

PMID- 19174725
TI  - Risk factors associated with sclerotomy leakage and postoperative hypotony after
      23-gauge transconjunctival sutureless vitrectomy.
AB  - PURPOSE: To investigate the incidence and risk factors of sclertomy leakage and
      postoperative hypotony after 23-gauge transconjunctival sutureless vitrectomy.
      METHODS: This was a retrospective study including 322 eyes of 292 patients who
      underwent 23-gauge transconjunctival sutureless vitrectomy by a single surgeon
      with minimum follow-up period of 1 month. The incidence and risk factors of
      intraoperative suture placement for leaking sclerotomies and postoperative
      hypotony (</=5 mmHg) were analyzed in association with seven clinical factors.
      RESULTS: Intraoperative suture placement was required for leaking sclerotomies in
      36 cases (11.2%) and was related to prior vitrectomy (OR = 7.5), young age (<50
      years) at operation (OR = 4.9), and vitreous base dissection (OR = 3.5). The
      incidences of postoperative hypotony were 11.3% at 2 hours, 6.5% at 5 hours, 3.8%
      at 1 day, and 0% at 1 week. Myopia and gas tamponade were associated with early
      postoperative hypotony. No complications developed related to sclerotomy leakage
      or postoperative hypotony. CONCLUSIONS: The risk factors of intraoperative
      sclerotomy leakage requiring suture placement after 23-gauge transconjunctival
      sutureless vitrectomy are prior vitrectomy, a young age at operation, and
      vitreous base dissection. Caution should be exercised to ensure the detection of
      sclerotomy leakage and hypotony in cases with these risk factors.

PMID- 19174726
TI  - Clinical features and surgical outcomes of pediatric rhegmatogenous retinal
      detachment.
AB  - PURPOSE: To evaluate the clinical features and functional and anatomical outcomes
      after surgical intervention in pediatric rhegmatogenous retinal detachment.
      METHODS: In this retrospective case series, pediatric patients with
      rhegmatogenous retinal detachment who had surgical intervention were included.
      Cases were categorized into five main etiology groups: congenital or
      developmental (48 eyes); trauma (54 eyes); myopia alone (12 eyes); previous
      intraocular surgery (10 eyes); and miscellaneous (3 eyes). Patients' demographic,
      clinical, and surgical outcomes, as well as fellow eye findings were evaluated.
      RESULTS: One hundred twenty-seven eyes of 108 patients (mean age: 12.1 +/- 4.1
      year, 80.6% male) were included. Scleral buckling was the initial procedure in
      31% of eyes and vitrectomy in 63%. Mean follow-up was 34 +/- 21 months (median 33
      months). Retinal reattachment at last follow-up was achieved in 74.9% of eyes.
      Visual acuity was >/=20/200 in 14% of eyes preoperatively and in 47.9% of eyes at
      final follow-up (P = 0.001). Retinal pathologies (mostly lattice degeneration)
      were noted in 82.2% of fellow eyes. CONCLUSION: Trauma and congenital
      developmental anomalies were the leading etiologies in pediatric rhegmatogenous
      retinal detachment in this review. Despite the complexity of rhegmatogenous
      retinal detachment and presence of vision-threatening anomalies, anatomic and
      functional outcomes were acceptable. Regular ophthalmoscopy of the sound eye is
      recommended for children at risk.

PMID- 19174727
TI  - Understanding the dynamics of condom use among female sex workers in China.
AB  - OBJECTIVES AND BACKGROUND: Condom use within the context of commercial sex work
      is a complex issue. Drawing on a hypothesized theoretical model that combines
      concepts from the health belief model and social cognitive theory, this study
      examines the complex relationships between multiple levels of determinant factors
      of condom use with clients among female sex workers in China. METHODS: Data were
      collected through the baseline survey of an HIV prevention project among 454
      establishment-based female sex workers in a rural county of Guangxi, China in
      2004. Path analysis was performed to test the hypothesized model that specifies
      relationships between all observed variables. RESULTS: Within the context of this
      study's model, STD/HIV knowledge and condom use skills were related to self
      efficacy which in turn related to condom use. Susceptibility/severity was related
      to perceived benefits of unprotected sex. Perceived benefits were in turn
      inversely related to condom use. STD/ HIV knowledge, condom use skills, and
      susceptibility/severity had no direct effect on condom use. Their effects on
      condom use were mediated by self-efficacy and perceived benefits. Self-efficacy
      was not associated with perceived benefits of unprotected sex. Perceived
      establishment-level support was positively related to condom use. CONCLUSIONS:
      Self-efficacy, perceived benefits of unprotected sex, and perceived establishment
      level support are proximate determinants of condom use among female sex workers.
      Future HIV prevention interventions should integrate these factors into
      conceptual frameworks.

PMID- 19174728
TI  - Normalizing HIV testing in a busy urban sexually transmitted infections clinic.
AB  - BACKGROUND: Increased awareness of HIV serostatus is a cornerstone of HIV
      prevention efforts. Thus, routine HIV testing in clinical settings has been
      identified as a priority. We report on our experience with making rapid HIV
      testing a routine procedure in a large STI clinic. METHODS: A series of
      logistical changes were implemented to enhance HIV testing uptake, including
      introduction of rapid testing, changes in sequence of clinical procedures, and an
      opt-out consent process. The impact of these changes on HIV testing was measured
      by the ratio of HIV testing and syphilis RPR testing, with the latter defined as
      the gold standard of routine testing in an STI clinic setting. RESULTS: Over time
      and in relationship to the introduction of clinic changes, the HIV/RPR ratio
      increased from 0.79 at baseline to 0.96 after full implementation. Overall HIV
      positivity rates did not vary significantly over time. CONCLUSION: After the
      introduction of several changes in clinic procedures, we experienced an increase
      HIV testing uptake relative to routine syphilis testing. In STI clinics, HIV
      testing can be made as normal as other routine STI testing.

PMID- 19174729
TI  - HIV incidence rates and risk factors for urban women in Zambia: preparing for a
      microbicide clinical trial.
AB  - OBJECTIVES: A preparedness study was conducted to evaluate the suitability of
      sites and populations following the same study procedures intended for a larger
      scale microbicide efficacy trial. In the process the study evaluated human
      immunodeficiency virus (HIV) incidence, prevalence, and risk profiles for HIV
      acquisition among young women in urban Zambia. METHODS: Women aged 16 to 49 years
      were screened for participation in the study that involved HIV/sexually
      transmitted infection testing and the assessment of sexual behavioral
      characteristics. Two hundred thirty-nine eligible women were enrolled and
      followed up for 12 months. RESULTS: Baseline HIV prevalence at screening was
      38.7% (95% CI: 34.2%-43.3%). The highest age-specific prevalence of HIV was 54.1%
      (95% CI: 46.3%-61.8%) seen in women aged 26 to 34 years. HIV incidence was 2.6%
      per 100 woman years. Pregnancy rates were high at 17.4 per 100 woman years (95%
      CI: 12.2-24.1). CONCLUSION: It was concluded that our general population sample,
      characterized by high HIV prevalence and ongoing incidence rates despite
      receiving regular risk reduction counseling and free condoms qualifies for future
      microbicide studies.A microbicide preparedness study conducted in Lusaka, Zambia
      found high HIV prevalence and appreciable HIV incidence in a population of women
      in an urban setting.

PMID- 19174730
TI  - Alternative approaches to partner notification, diagnosis, and treatment:
      perspectives of New York County Health Departments, 2007.
AB  - OBJECTIVES: The Centers for Disease Control and Prevention is encouraging states
      to consider patient-delivered partner therapy (PDPT) as a treatment option for
      Chlamydia and gonorrhea. We sought to assess current sexually transmitted disease
      (STD) control practices in New York State county health departments, and gather
      their perspectives on PDPT and alternative interventions. METHODS: A cross
      sectional study reviewed county websites to assess STD service information
      provided. County STD programs were surveyed from January to March 2007 by
      telephone to determine conditions diagnosed and treated, current partner
      notification practices, and to assess perspectives on PDPT and alternative
      interventions. Descriptive statistics were computed. RESULTS: County officials
      were divided about legalizing PDPT, with 45% for, 45% against, and 10% undecided.
      Reasons for support included the perception PDPT would result in more infections
      treated (61%) and improved STD control (29%). Reasons for lack of support
      included potential contraindication/side effects (28%), potential for medication
      not reaching partners (28%), and malpractice risk (20%). Stratified analysis by
      STD morbidity levels showed high morbidity counties were against legalization
      (67%). PDPT with health department follow-up of partners was the most preferred
      strategy, followed by patient distribution of educational materials and express
      care for partners in STD clinics; PDPT alone was the least preferred. New York
      State County officials' perspectives on PDPT are polarized along lines of program
      size and morbidity. CONCLUSIONS: Further research on alternative partner
      intervention strategies and discussion of PDPT is necessary to develop a forward
      thinking strategic plan for STD control in the state.

PMID- 19174731
TI  - What about the partners of women with abnormal Pap or positive HPV tests?
AB  - BACKGROUND: Because high-risk HPV is highly prevalent in the general population,
      usually transient, and rarely causes clinical symptoms, and because diagnostic
      and treatment options for HPV in men are lacking, partner notification is not
      useful for preventing transmission or protecting the health of male partners.
      METHODS: We conducted a nationally representative survey of clinicians in 7
      specialties that perform cervical cancer screening. Providers were asked whether
      they recommend that women with an abnormal Pap or positive HPV test inform sex
      partners of the infection or refer partners to a clinician. RESULTS: A large
      proportion of providers in all 7 specialties encourage women with either an
      abnormal Pap or a positive HPV test to tell their sex partners to see a
      clinician, ranging from 48% to 73% across specialties. Providers who perform
      reflex HPV testing were more likely to recommend that patients with an ASCUS Pap
      inform their partners of test results if an HPV test was positive than if it was
      negative (66%-83% vs. 29%-50%); providers who perform adjunct HPV testing were
      more likely to recommend that patients with a normal Pap inform their partners if
      an HPV test was positive than if it was negative (72%-92% vs. 30%-52%).
      CONCLUSIONS: Most providers advise patients with cervical cancer screening tests
      suggestive of HPV infection to notify their sex partners and to refer them to a
      clinician. Guidelines are needed for providers to clarify any rationale for
      clinical evaluation of male partners, including that informing partners has a
      limited role in the control of HPV transmission or in preventing adverse health
      outcomes in the male partner.

PMID- 19174732
TI  - Alternative approaches to partner notification, diagnosis, and treatment:
      pharmacists' perspectives on proposed patient delivered partner therapy in New
      York State, 2007.
AB  - BACKGROUND: Supported by the American Medical Association, patient delivered
      partner therapy (PDPT) is becoming legal in many states. For some individuals
      exposed to sexually transmitted infections, the pharmacist may become the sole
      point of contact with the medical system. METHODS: To determine pharmacists'
      perceptions about PDPT, education on sexually transmitted infections, and
      potential barriers that need to be addressed in pharmacies for successful
      implementation of PDPT, we conducted a survey of pharmacists and observed privacy
      related spaces in pharmacies. In 8 counties of the Capital Region, all community
      pharmacies were invited to participate. In 8 additional counties convenience
      sampling was utilized. The response proportion was 67.3% overall. RESULTS: Of the
      193 pharmacists responding to the survey, 63% supported PDPT for Chlamydia and
      78% do not want a behind-the-counter status for Chlamydia antibiotics. The
      majority (88%) of pharmacists want prescriptions marked as PDPT to alert them to
      counseling needs. About half the pharmacists reported they would automatically
      submit PDPT prescriptions to insurance company, a confidentiality issue. The
      barrier cited most often to patient counseling was time (49%). CONCLUSIONS:
      Pharmacists are open to considering PDPT as part of their professional functions.
      Although pharmacists need additional sexually transmitted infections education in
      general, capacity for this training can be developed. Confidentiality issues
      remain a priority issue to address to protect individuals treated through PDPT.

PMID- 19174733
TI  - Increased knowledge of safe and appropriate penicillin injection after viewing
      brief instructional video titled "how to inject Bicillin LA".

PMID- 19174734
TI  - Sex work, syphilis, and seeking treatment: an opportunity for intervention in HIV
      prevention programming in Karnataka, South India.
AB  - OBJECTIVES: To measure the determinants of syphilis among female sex workers
      (FSWs) in the state of Karnataka, South India. METHODS: During 2004-2006, cross
      sectional surveys were administered to 2312 FSWs across 5 districts in the state,
      in the context of a large-scale HIV preventive intervention program. Demographic
      and behavioral information, and serum (for syphilis, HSV-2 and HIV) and urine
      specimens (for Neisseria gonorrhoeae and Chlamydia trachomatis) were obtained.
      RESULTS: The prevalences of lifetime (TPHA positive) and active (RPR and TPHA
      positive) syphilis were 25.3% and 9.6%, respectively. There was considerable
      variation in the prevalence between districts, ranging from 10.9% to 37.4%
      lifetime, and 3.4% to 24.9% active infection. Factors associated with lifetime
      syphilis were older age, longer duration of sex work, illiteracy, client volume,
      practising sex work in >1 city, and sex work typology (public solicitation
      followed by brothel or lodge-based sex). The same typology, client volume,
      illiteracy, and having been widowed, divorced or deserted, were predictive of
      active infection. Of the 976 women who had symptoms of an STI, 78.8% had sought
      medical treatment, behavior that was protective for both outcomes. HIV infection
      was strongly associated with lifetime (OR 2.0; 95% CI: 1.6-2.6) and active
      syphilis (OR 2.1; 95% CI: 1.5-2.9). CONCLUSIONS: Despite reasonable treatment
      seeking behavior, the high prevalence of syphilis has necessitated enhanced
      outreach efforts for FSWs and acceleration of the implementation of syphilis
      screening. Mobilizing resources to enhance syphilis control will not only reduce
      the burden of syphilis morbidity, but should impact in reducing HIV transmission.

PMID- 19174735
TI  - Determinants of newly detected human papillomavirus infection in HIV-infected and
      HIV-uninfected injection drug using women.
AB  - BACKGROUND: We sought to identify factors associated with newly detected human
      papillomavirus (HPV) infection in a high-risk cohort of injection drug using
      women in Baltimore, MD. METHODS: We studied 146 HIV-infected and 73 HIV
      uninfected female participants in a 5-year prospective HIV natural history study.
      We examined the association of sexual and nonsexual risk factors and newly
      detected type-specific HPV infection as determined by consensus PCR between
      consecutive visits. RESULTS: Newly detected HPV was more common among HIV
      infected versus HIV-uninfected women (30% and 6%, respectively; P <0.01). Among
      the entire cohort, recent crack use (OR, 1.7; 95% CI, 1.1-2.6) and HIV
      infection/CD4 cell count were independent predictors for new HPV detection (HIV
      uninfected as reference, OR, 4.6; 95% CI, 2.3-8.9, OR, 5.4; 95% CI, 2.8-10.3, and
      OR, 10.9; 95% CI, 5.5-21.7 for HIV-infected CD4 >500, 200-500, and <200,
      respectively). Among HIV-uninfected women, recent marijuana use was an
      independent predictor of newly detected HPV infection (OR, 3.5; 95% CI, 1.3-9.5).
      CONCLUSIONS: Newly detected HPV clearly increased with greater immunosuppression
      in HIV-infected injection drug users. Larger studies of HIV-uninfected and
      infected high-risk individuals are needed to clarify the independent associations
      of crack and marijuana use with new (or reactivated) HPV infection.

PMID- 19174736
TI  - 100% oxygen inhalation protects against zymosan-induced sterile sepsis in mice:
      the roles of inflammatory cytokines and antioxidant enzymes.
AB  - Sepsis is a leading cause of death in patients with critical illness. However,
      there is no effective therapy available. Recent studies have suggested that
      ventilation with 100% oxygen (Oxy) can improve the survival rate and organ
      function in several shock models. However, a lot of work is necessary to be done
      before its clinical application, and its detailed mechanism remains to be
      clarified. In the present study, we showed that 100% Oxy inhalation for 2 or 3 h
      starting at 4 and 12 h after zymosan (ZY) injection, respectively, prevented the
      abnormal changes of serum biochemical parameters, tissue oxygenation, and organ
      histopathology, and improved the 14-day survival rate from 10% to 60% to 80% in
      mice. However, 100% Oxy inhalation for 1 or 4 h starting at the same time points
      has little preventive effects. We also showed that twice 100% Oxy inhalation for
      2 or 3 h attenuated the increase of inflammatory cytokines and precluded the
      downregulation of antioxidant enzymatic activities. We further showed that the
      therapeutic time window of Oxy treatment against sterile sepsis was less than 12
      h after ZY injection. We conclude that 100% Oxy inhalation for 2 or 3 h starting
      4 and 12 h after ZY injection, respectively, protects against ZY-induced sterile
      sepsis via regulating inflammatory cytokines and antioxidant system in mice. The
      present results may provide a potential cue for developing more effective
      therapeutic strategies for patients with sepsis.

PMID- 19174737
TI  - Attenuation of pulmonary inflammation after exposure to blast overpressure by N
      acetylcysteine amide.
AB  - Lung contusion is a common problem from blunt chest trauma caused by mechanical
      forces and by exposure to blast overpressure, often with fatal consequences. Lung
      contusion is also a risk factor for the development of pneumonia, severe clinical
      acute lung injury (ALI), and acute respiratory distress syndrome (ARDS).
      Infiltrating neutrophils are considered to be central mediators of lung injuries
      after blunt trauma. Recent studies have demonstrated that antioxidants reduced
      pulmonary inflammation in different models of lung damage. This study examined
      the effect of antioxidant N-acetylcysteine amide (NACA) on the progression of
      lung inflammation after exposure to a moderate level of blast overpressure (140
      kPa). Rats were administered with NACA (i.p. 100 mg/kg) or placebo (PBS) 30, 60
      min and 24 h after exposure. Nonblasted sham-injected animals served as controls.
      Neutrophil infiltration measured by myeloperoxidase (MPO) activity in the lung
      was significantly increased at 2 days after blast and returned to controls at 8
      days. This increase corresponded with activation of integrin CD11b mRNA and lung
      inflammatory chemokine mRNA expression; macrophage inflammatory protein-1 (MIP
      1), monocyte chemotactic peptide-1 (MCP-1), and cytokine-induced neutrophil
      chemoattractant-1 (CINC-1). At 8 days, all inflammatory mediators returned to
      control levels. In addition, expression of heme oxygenase-1 (HO-1) mRNA increased
      at 2 days after exposure. No changes were detected in the lung manganase
      superoxide dismutase (MnSOD) or glutathione reductase (GR) mRNA expression after
      blast. N-Acetylcysteine amide significantly reduced infiltration of neutrophils
      and CD11b mRNA activation in lungs, and completely blocked activation of MIP-1,
      MCP-1 and CINC-1 mRNA. The relatively higher inhibition of chemokine mRNAs
      compared with reduction in MPO activity and CD11b is in accordance with an
      antioxidant effect of NACA on reactive oxygen species (ROS) accumulation, rather
      than by an effect on neutrophil sequestration. The inhibition of HO-1 mRNA
      activation after blast was likely also related to the drug antioxidant effect.

PMID- 19174738
TI  - Lung contusion: inflammatory mechanisms and interaction with other injuries.
AB  - This article reviews current animal models and laboratory studies investigating
      the pathophysiology of lung contusion (LC), a common and severe condition in
      patients with blunt thoracic trauma. Emphasis is on studies elucidating cells,
      mediators, receptors, and processes important in the innate pulmonary
      inflammatory response that contribute to LC injury. Surfactant dysfunction in the
      pathogenesis of LC is also discussed, as is the potential role of epithelial cell
      or neutrophil apoptosis. Studies examining combination injuries where LC is
      exacerbated by secondary insults such as gastric aspiration in trauma patients
      are also noted. The need for continuing mechanism-based research to further
      clarify the pathophysiology of LC injury, and to define and test potential
      therapeutic interventions targeting specific aspects of inflammation or
      surfactant dysfunction to improve clinical outcomes in patients with LC, is also
      emphasized.

PMID- 19174739
TI  - Afferent pathways involved in cardiovascular adjustments induced by hypertonic
      saline resuscitation in rats submitted to hemorrhagic shock.
AB  - The peripheral hyperosmolarity elicited by intravenous infusion of hypertonic
      saline (HS) can be beneficial in treating hemorrhagic shock. However, the neural
      mechanisms involved in this resuscitation remain unknown. The present study
      sought to determine the effects of selective baroreceptor denervation on arterial
      blood pressure response during HS resuscitation in rats submitted to hemorrhagic
      shock. Male Wistar rats (280-320 g) were anesthetized with thiopental sodium (40
      mg/kg, i.v.), and the femoral artery and jugular vein were cannulated for MAP and
      heart rate recording and HS infusion (3 mol/L NaCl; 0.18 mL/100 g body weight, >2
      min). Hemorrhagic shock was obtained by withdrawing blood over 30 min until a MAP
      of 60 mmHg was obtained. This level of MAP was maintained for a further 30 min
      through subsequent blood withdrawal or reinfusion. Next, animals were divided
      into selective aortic and/or carotid denervation or sham groups before infusing
      HS. Results showed that in the sham group (n = 12), HS infusion increased MAP to
      levels close to baseline (from 65 +/- 3 to 112 +/- 5 mmHg, 10 min after HS). In
      the aortic denervated group (n = 10), HS infusion also increased MAP (from 54 +/-
      3 to 112 +/- 5 mmHg, 10 min after HS). In contrast, in the carotid denervation
      group (n = 8), the increase in MAP induced by HS infusion was abolished (from 53
      +/- 3 to 73 +/- 12 mmHg, 10 min after HS). These results indicate that in
      hemorrhaged rats, HS infusion produces a pressor effect that is likely to be
      mediated through carotid rather than aortic baroreceptors.

PMID- 19174740
TI  - A new dynamic porcine model of meningococcal shock.
AB  - The objective of this study was to establish a porcine analog of human
      meningococcal sepsis for pathophysiological investigations and possible future
      therapy in severe sepsis. Heat-killed Neisseria meningitidis was continuously
      infused in sublethal concentrations into 10 anesthetized 30-kg pigs (sepsis
      group). The dose was doubled every 30 min. Six pigs received saline only (control
      group). The changes described in the succeeding paragraphs were observed in the
      sepsis group but not in the control group. MAP was aimed to be kept normal by
      fluid infusion but declined after 3 h in parallel with a decrease in systemic
      vascular resistance. Pulmonary arterial pressure increased considerably after 30
      to 45 min. A massive plasma extravasation was shown by increased hematocrit and a
      50% reduction in plasma albumin content. Fluid accumulated in lungs, muscles, and
      jejunum, as shown by increased wet-dry ratios. Peak inspiratory pressures and
      fraction of inspired oxygen had to be increased. The cytokines TNF-alpha, IL
      1beta, IL-6, IL-8, IL-10, and IL-12 increased markedly. Neutrophils fell to zero
      levels, and platelets were markedly reduced. Thrombin-antithrombin complexes
      increased notably after 120 min. This is the first large animal model of sepsis
      using whole Neisseria meningitidis. The model simulates well central aspects of
      human meningococcal sepsis and could be used for future interventional studies.

PMID- 19174741
TI  - Second-generation sulfonylureas preserve inhibition of mitochondrial permeability
      transition by the mitochondrial K+(ATP) opener nicorandil in experimental
      myocardial infarction.
AB  - Openers of K+(ATP) channels protect the myocardium from I/R injury. Sulfonylureas
      are known as potent blockers of K(ATP) channels. We investigated whether 1)
      mitochondrial permeability transition pore may be involved in the protection
      afforded by the mitoK+(ATP) opener nicorandil and 2) whether sulfonylureas may
      prevent this beneficial effect. Anesthetized New Zealand White rabbits underwent
      30 min of coronary artery occlusion, followed by 60 (isolated mitochondria) or
      240 min (infarct size) of reperfusion. They received an administration of either
      saline (control) or nicorandil (0.5 mg kg(-1), i.v.) 15 min before ischemia. Each
      control and nicorandil group was divided in four subgroups pretreated by either
      saline, glibenclamide (Glib; 1 mg kg(-1)), gliclazide (Glic; 1 mg kg(-1)), or
      glimepiride (Glim; 5 microg kg(-1)) 10 min before this. Infarct size was assessed
      by triphenyltetrazolium chloride staining. Mitochondria were isolated from the
      area at risk for further assessment of the calcium retention capacity.
      Glibenclamide (35 +/- 8), but neither Glic (61 +/- 9) nor Glim (48 +/- 7),
      reversed the improvement in calcium retention capacity due to nicorandil (58 +/-
      10 vs. 27 +/- 8 nmoles CaCl2 mg(-1) proteins in control). Infarct size reduction
      by nicorandil (32% +/- 6% vs. 65% +/- 6% of area at risk) was abolished by Glib
      (55 +/- 5) but not by Glic (37 +/- 3) or Glim (31 +/- 5). These data suggest that
      1) the protective effect of nicorandil involves the inhibition of the
      mitochondrial permeability transition pore and 2) that unlike Glib, second
      generation sulfonylureas preserve this cardioprotection.

PMID- 19174742
TI  - Peroxisome proliferator-activated receptor-gamma ligands 15-deoxy-delta(12,14)
      prostaglandin J2 and pioglitazone inhibit hydroxyl peroxide-induced TNF-alpha and
      lipopolysaccharide-induced CXC chemokine expression in neonatal rat cardiac
      myocytes.
AB  - Ligands for peroxisome proliferator-activated receptor gamma (PPAR-gamma) such as
      prostaglandin metabolite 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) or
      thiazolidinedione pioglitazone have been identified as a new class of anti
      inflammatory compounds with possible clinical applications. Reactive oxygen
      species play an important role in the generation of cellular damage by induction
      of proinflammatory cytokines and chemokines during myocardial I/R. These events
      were preceded by activation of the transcription factors nuclear factor (NF)
      kappaB pathway. It has been suggested that myocardium overproduces TNF-alpha
      after I/R, and locally produced TNF-alpha is sufficient to cause severe
      impairment of cardiac function. LPS-induced CXC chemokine (LIX) is a rodent
      chemokine with potent neutrophil-chemotactic activity. Based on this concept, we
      examined the effects of 15d-PGJ2 and pioglitazone on oxidative stress-induced TNF
      alpha and LIX expression in neonatal rat cardiac myocytes. Pretreatment of
      myocytes with 15d-PGJ2 or pioglitazone decreased hydrogen peroxide-induced TNF
      alpha and LIX production (mRNA and protein) in a concentration-dependent manner.
      The beneficial effects of both ligands were associated with reduction of hydrogen
      peroxide-induced NF-kappaB activation. Treatment with 15d-PGJ2, but not
      pioglitazone, caused dose-dependent activation of heat shock factor 1, which
      could render cells unresponsive to stimulation of NF-kappaB. The cytoprotection
      afforded by pioglitazone was attenuated by the PPAR-gamma antagonist GW9662,
      which failed to affect the beneficial effects afforded by 15d-PGJ2. Taken
      together, these results demonstrate that treatment with these chemically distinct
      ligands of PPAR-gamma results in diverse anti-inflammatory mechanisms.

PMID- 19174743
TI  - Improving effect of pretreatment with yiqifumai on LPS-induced microcirculatory
      disturbance in rat mesentery.
AB  - Yiqifumai is a traditional Chinese medicine compound preparation used for the
      treatment of various vascular diseases in China. However, little is known
      regarding its role in microcirculation. The present study investigated the effect
      of pretreatment of yiqifumai on rat mesentery microcirculatory disturbance
      induced by LPS. Male Wistar rats were continuously infused with LPS (5 mg kg(-1)
      h(-1)). The parameters evaluated included diameter of and red blood cell velocity
      in venules, leukocyte adhesion to venular wall, dihydrorhodamine 123 (DHR)
      fluorescence in the venular walls, fluorescein isothiocyanate-albumin leakage,
      and mast cell degranulation, which were observed by an inverted intravital
      microscope. CD11b/CD18 expression on neutrophils was examined using flow
      cytometry. In some rats, yiqifumai (5, 30, or 80 mg kg(-1)) was given in one shot
      10 min before LPS infusion. After infusion of LPS, the number of leukocytes
      adherent to venular wall, the intensity of DHR fluorescence in the venular walls,
      albumin leakage from venules, and degranulated mast cells were significantly
      increased, whereas the red blood cell velocity in venule was decreased.
      Pretreatment with high-dose yiqifumai (80 mg kg(-1)) significantly reduced the
      number of adherent leukocytes, the intensity of DHR fluorescence, degranulation
      of mast cell, albumin leakage, and the expression of CD11b/CD18, whereas the
      yiqifumai of medium dose (30 mg kg(-1)) only inhibited leukocyte adhesion to the
      venular wall. The results suggested that pretreatment with yiqifumai attenuated
      microcirculatory disturbance induced by LPS. This effect may be associated with
      yiqifumai's inhibition effect on reactive oxygen species production, leukocyte
      adhesion, and mast cell degranulation.

PMID- 19174744
TI  - Gender difference in granulocyte dynamics and apoptosis and the role of IL-18
      during endotoxin-induced systemic inflammation.
AB  - Delayed granulocyte apoptosis is implicated in persistent inflammation. Although
      it is known that males develop sepsis more easily than females, the mechanism for
      this is not fully understood. Serum IL-18 levels correspond to severity of
      systemic inflammation. The purpose of this study was to elucidate gender
      differences and the effects of IL-18 on granulocyte dynamics and apoptosis. Male
      and female wild-type (WT) and IL-18 knockout (KO) mice were injected
      intraperitoneally with LPS. Bone marrow cells, peripheral blood, and peritoneal
      cells were then collected at different times up to 24 h after injection.
      Apoptosis was assessed by annexin V staining using three-color flow cytometry
      with differentiated granulocyte-specific Gr-1, B-lymphocyte-specific B220, and
      macrophage-specific F4/80 antibodies. Male WT mice were more susceptible to
      endotoxin than female WT mice (survival rate, 41% in male WT and 84% in female
      WT). Male WT mice showed stronger responses than females in myeloid
      differentiation, release of myeloid cells from the bone marrow into the
      periphery, and migration into the inflammatory peritoneal cavity. Male mice also
      showed greater inhibition of granulocyte apoptosis in the peritoneal cavity,
      which might also contribute to the higher numbers of those cells present. A
      comparison between WT and KO mice revealed that the gender difference in these
      myeloid cells/granulocytes' behaviors was independent of endogenous IL-18.
      Nevertheless, levels of IL-18 in the blood of WT mice were significantly higher
      in males than in females after intraperitoneal LPS, and the survival rate was
      significantly higher in KO mice compared with WT mice only in males. This
      indicates that endogenous IL-18 production decreases survival only in males.
      Thus, excessive myeloid/granulocyte immunity independent of IL-18 and other IL-18
      dependent life-threatening factors in males should be taken into account as
      therapeutic targets during systemic inflammatory states.

PMID- 19174745
TI  - The novel inosine analogue INO-2002 exerts an anti-inflammatory effect in a
      murine model of acute lung injury.
AB  - Endogenous purines, including inosine, have been shown to exert immunomodulatory
      and anti-inflammatory effects in a variety of disease models. The dosage of
      inosine required for these effects has been shown to be between 200 and 600 mg
      kg(-1) because of the rapid metabolism of inosine in vivo. The aim of this study
      was to determine whether a metabolic resistant purine analog, INO-2002, exerts
      anti-inflammatory effects in an animal model of acute respiratory distress
      syndrome. Mice challenged with intratracheal LPS (50 microg) were treated with
      INO-2002 (30 or 100 mg kg(-1), i.p.) in divided doses at either 1 and 12 h or at
      5 and 16 h. After 24 h, bronchoalveolar lavage fluid was obtained to measure
      leukocyte infiltration by myeloperoxidase levels, lung edema by protein levels,
      and proinflammatory chemokine (macrophage inflammatory protein 1alpha) and
      cytokine (TNF-alpha, IL-1, and IL-6) levels. INO-2002 (30 and 100 mg kg(-1))
      reduced the LPS-mediated infiltration of leukocytes and edema as evidenced by
      bronchoalveolar lavage fluid reduction in levels of myeloperoxidase and protein.
      INO-2002 also downregulated expression of the proinflammatory mediators
      macrophage inflammatory protein 1alpha, TNF-alpha, IL-1, and IL-6. Delaying the
      start of treatment by 5 h after LPS administration affected the potency of INO
      2002 protective effects, with 100 but not 30 mg kg(-1) having anti-inflammatory
      effects. The inosine analog INO-2002 largely suppressed LPS-induced inflammation
      in vivo at doses lower than those needed for the naturally occurring purine
      inosine. These data support the proposal that purine analogs, resistant to
      metabolic breakdown, may represent a useful addition to the therapy of acute
      respiratory distress syndrome.

PMID- 19174747
TI  - Extended septic thrombophlebitis in a patient with duplicated inferior vena cava:
      case report and review of literature.
AB  - Duplication is one of the congenital abnormalities of the inferior vena cava
      (IVC) and is reported to be associated with deep venous thrombosis (DVT). We
      report a case who was admitted for carbamazepine-induced toxic epidermal
      necrolysis. The patient had persistent fever caused by septic thrombophlebitis
      extending from the left femoral vein to the duplicated left IVC. The fever and
      thrombosis resolved under combined treatment with antibiotics and anticoagulants,
      without further complication of symptomatic pulmonary embolism. This is the first
      case in patient with IVC duplication complicated by DVT induced by septic
      thrombophlebitis, which was not seen in the nine cases of IVC duplication
      reported previously.

PMID- 19174749
TI  - How can we improve the perioperative management of patients undergoing non
      cardiac vascular surgery?

PMID- 19174750
TI  - Buflomedil: potential new indications for an old agent.
AB  - Our understanding of vascular pathophysiology has significantly improved during
      the past two decades. Patients with type 2 diabetes mellitus have an increased
      vascular risk and a series of modifiable risk factors play a crucial role in the
      atherosclerotic process. The microvascular dysfunction in diabetes results in
      increased vascular permeability and impaired regulation of blood flow and
      vascular tone. These changes culminate in nephropathy, retinopathy and neuropathy
      and probably contribute to the increase vascular morbidity and mortality in this
      population. Moreover, studies in the skin microvasculature suggest that this
      microvascular dysfunction contributes significantly to the pathogenesis of
      diabetic foot. Several studies showed a beneficial effect of vasoactive drugs,
      including buflomedil, in non-diabetic patients. However, it remains to be
      established whether these drugs could also be beneficial in the diabetic
      population, especially in the early stages of diabetes.

PMID- 19174755
TI  - Effect of different sessions of cardiac rehabilitation on exercise capacity in
      patients with percutaneous transluminal coronary angioplasty.
AB  - AIM: Exercise capacity after training has been reported to improve after cardiac
      rehabilitation (CR) in patients with coronary artery disease (CAD). The purpose
      of this study was to evaluate the effect of different sessions of an exercise
      based CR program on exercise capacity in CAD patients after elective percutaneous
      transluminal coronary angioplasty (PTCA). METHODS: In a university hospital, 440
      patients who were enrolled in an exercise-based CR program (phase 2) after
      elective PTCA, were retrospectively evaluated. Two hundred-eighty-six subjects
      were categorized based on the completion of CR sessions (group A, B and C
      completing 5, 10 and 24 sessions, respectively). The main outcome measures were
      exercise training energy expenditure (ETEE) and treadmill velocity of first and
      last session of CR. Pearson's chi(2) test, Kruskall-Wallis test, paired Student's
      t test and multivariate analysis were used. RESULTS: All patients showed
      significant improvements in ETEE and treadmill velocity from baseline to follow
      up sessions. A significant group effect on exercise parameters was detected
      between all the three CR groups (P<0.0001). On follow-up, the ETEE and treadmill
      velocity had statistically significant correlation with the number of completed
      sessions, age and gender (P<0.001). CONCLUSION: The present study indicated that
      improvement in exercise capacity occurs in both gender from baseline to the last
      session, regardless of clinical characteristics of patients with PTCA. When
      controlled for other factors, calorie expenditure and treadmill velocity was
      independently associated with the number of completed sessions, age and gender.

PMID- 19174756
TI  - Sagittal plane kinematic analysis of the six-minute walk test: a classification
      of hemiplegic gait.
AB  - AIM: The aim of this study was to propose a kinematic classification of gait
      according to six minute walk test performance. METHODS: Thirty-four hemiplegic
      subjects were enrolled. Six-minute walk test (SMWT), gait analysis and Walking
      Handicap Scale score (WHS) were measured. A k-means cluster analysis was used to
      classify the sample into three sub-groups which were homogeneous in spatio
      temporal parameters, kinematic variables, and which reflected three meaningful
      levels of walking competency. RESULTS: Three clusters were identified: low
      functioning walkers (Cluster 1) walked for 88-172 m; intermediate-functioning
      walkers (Cluster 2) walked for 180-302 m and high-functioning walkers (Cluster 3)
      were able to cover 349-430 m. The authors found homogeneous gait profiles in
      these subgroups. Between-group differences on kinematic data and WHS scores were
      also underlined. CONCLUSIONS: Cluster analysis was able to identify consistent
      gait characteristics of spatio-temporal, walking endurance and sagittal plane
      kinematic profiles in hemiplegic subjects and is useful for categorizing the
      levels of walking competency in these subjects.

PMID- 19174757
TI  - Comparative performance of two inhaler systems to assess distribution of
      convective ventilation by 99mTc-labeled aerosol scintigraphy in patients with
      airway obstruction.
AB  - AIM: Redistribution of convective ventilation, the leading disorder in airway
      obstruction, is a target of pharmacological and mechanical ventilation treatments
      for patients with chronic obstructive pulmonary disease (COPD). Convective
      ventilation is visualized by ventilation scintigraphy using radiolabeled aerosol
      particles that should ideally deposit in the terminal airspaces, but not in the
      conducting airways, and have no Brownian motion (which characterizes diffusive
      ventilation). Currently available commercial systems do not meet these
      requirements as they do not ensure an optimal size of aerosol droplets delivered
      at the mouthpiece. METHODS: A new inhaling system (FAI) was developed and
      designed so as to yield radioaerosol droplets with smaller particle size and to
      ensure more efficient aerosol delivery to the terminal airways than that obtained
      with a widely available commercial system (MMI). A cascade impactor was employed
      to measure the size of the radioactive droplets at the mouthpiece. Preliminary
      comparative validation was based on ventilation scintigraphy using the two
      systems (both followed by a standard lung perfusion scan) in control subjects and
      in patients with airway obstruction. The time required to reach a certain count
      rate in the lung fields (1 kc/s) was recorded by means of dynamic g camera
      acquisition during breathing. Subsequent static images allowed assessment of
      intrapulmonary distribution of ventilation (by both visual and quantitative
      evaluation) and of the ventilation/perfusion (V/Q) ratios relative to the upper,
      middle, and lower thirds of the lung fields. RESULTS. FAI yielded 99mTc-labeled
      droplets with a count median diameter of 1.4 microm and a geometric standard
      deviation of 2 microm , versus 3 microm and 2, respectively, produced by the
      commercial inhaler (MMI). The mean time to reach the 1 kc/s count rate was
      significantly shorter with the FAI than with the MMI both in control subjects
      (4.7+/-1.7 min versus 8.2+/-2 min, P<0.04) and in airway-obstructed patients
      (3.4+/-0.8 min versus 8.4+/-2 min, P<0.001). With the MMI, appreciable
      radioaerosol deposition in the large bronchi prevented reliable quantitative
      assessment of ventilation, even in the control subjects. With the FAI,
      radioaerosol deposition in the central large airways was never observed in the
      controls and was only sporadically or occasionally observed in patients with COPD
      or asthma, respectively. This feature allowed quantitative ventilation
      assessment. The FAI-generated radioaerosol particles reached the peripheral
      respiratory spaces more efficiently than those generated by MMI; on the
      ventilation scans, the FAI allowed better discrimination than the MMI of the
      different pathophysiologic conditions. CONCLUSION: These findings consistently
      indicate that the smaller-sized radiolabeled droplets generated by FAI, combined
      with the better breathing dynamics of the inhaler device, result in better
      overall performance as compared to the commercial system. This makes
      scintigraphic images obtained with the new device especially suitable for
      assessing convective ventilation in COPD patients, a particularly helpful feature
      for analytically describing the distribution patterns observed in airway
      obstructed patients and for evaluating the effects of drugs, mechanical
      ventilation, and other interventions in such patients.

PMID- 19174759
TI  - Enzyme replacement improves ataxic gait and central nervous system histopathology
      in a mouse model of metachromatic leukodystrophy.
AB  - Inherited deficiencies of lysosomal hydrolases cause lysosomal storage diseases
      (LSDs) that are characterized by a progressive multisystemic pathology and
      premature death. Repeated intravenous injection of the active counterpart of the
      deficient enzyme, a treatment strategy called enzyme replacement therapy (ERT),
      evolved as a clinical option for several LSDs without central nervous system
      (CNS) involvement. To assess the efficacy of long-term ERT in metachromatic
      leukodystrophy (MLD), an LSD with prevailing nervous system disease, we treated
      immunotolerant arylsulfatase A (ASA) knockout mice with 52 doses of either 4 or
      50 mg/kg recombinant human ASA (rhASA). ERT was tolerated without side effects
      and improved disease manifestations in a dose-dependent manner. Dosing of 4 mg/kg
      diminished sulfatide storage in kidney and peripheral nervous system (PNS) but
      not the CNS, whereas treatment with 50 mg/kg was also effective in the CNS in
      reducing storage in brain and spinal cord by 34 and 45%, respectively.
      Histological analyses revealed regional differences in sulfatide clearance. While
      70% less storage profiles were detectable, for example, in the hippocampal
      fimbria, the histopathology of the brain stem was unchanged. Both enzyme doses
      normalized the ataxic gait of ASA knockout mice, demonstrating prevention of
      nervous system dysfunctions that dominate early stages of MLD.

PMID- 19174760
TI  - Transient pretreatment with glucocorticoid ablates innate toxicity of
      systemically delivered adenoviral vectors without reducing efficacy.
AB  - More than 300 human clinical trials utilize recombinant adenoviruses (rAds) as a
      gene transfer vector, confirming that rAds continue to be of high clinical
      interest. A primary weakness of rAds is their known propensity to trigger an
      innate, proinflammatory immune response rapidly after high-dose, systemic
      administration. In this study, we investigated what affects that pre-emptive
      treatment with anti-inflammatory glucocorticoids might have upon Ad vector
      triggered inflammatory immune responses. We found that a simple pretreatment
      regimen with Dexamethasone (DEX) can significantly reduce most Ad-induced innate
      immune responses. DEX prevented rAd induction of systemic cytokine/chemokine
      releases in a dose-dependent fashion, with higher dosages preventing rAd
      induction of acute thrombocytopenia, endothelial cell activation, proinflammatory
      gene induction, and leukocyte infiltration into transduced organs. Transient
      glucocorticoid pretreatment also significantly reduced rAd-induced adaptive
      immune responses, including a decreased induction of Ad-neutralizing antibodies
      (NAbs). Importantly, use of DEX did not reduce the efficacy of rAd-mediated gene
      transduction nor rAd-derived transgene expression. Our results demonstrate that a
      simple, pre-emptive and transient glucocorticoid pretreatment is a viable
      approach to reduce rAd-associated acute toxicities that currently limit the use
      of Ad vectors in systemic clinical applications.

PMID- 19174761
TI  - Improved retinal function in a mouse model of dominant retinitis pigmentosa
      following AAV-delivered gene therapy.
AB  - Mutational heterogeneity represents one of the greatest barriers impeding the
      progress toward the clinic of gene therapies for many dominantly inherited
      disorders. A general strategy of gene suppression in conjunction with replacement
      has been proposed to overcome this mutational heterogeneity. In the current
      study, various aspects of this strategy are explored for a dominant form of the
      retinal degeneration, retinitis pigmentosa (RP), caused by mutations in the
      rhodopsin gene (RHO-adRP). While > 200 mutations have been identified in
      rhodopsin (RHO), in principle, suppression and replacement may be employed to
      provide a single mutation-independent therapeutic for this form of the disorder.
      In the study we demonstrate in a transgenic mouse simulating human RHO-adRP that
      RNA interference-based suppression, together with gene replacement utilizing the
      endogenous mouse gene as the replacement, provides significant benefit as
      evaluated by electroretinography (ERG). Moreover, this is mirrored histologically
      by preservation of photoreceptors. AAV-based vectors were utilized for in vivo
      delivery of the therapy to the target cell type, the photoreceptors. The results
      demonstrate that RNAi-based mutation-independent suppression and replacement can
      provide benefit for RHO-adRP and promote the therapeutic approach as potentially
      beneficial for other autosomal dominantly inherited disorders.

PMID- 19174762
TI  - Tolerance induction using lentiviral gene delivery delays onset and severity of
      collagen II arthritis.
AB  - The treatment of rheumatoid arthritis remains suboptimal; thus there is
      considerable interest in the development of strategies that mediate tolerance to
      autoantigens. Using lentiviral gene transfer in vivo, we expressed the
      immunodominant epitope of collagen type II (CII) on major histocompatibility
      complex class II molecules (MHC II) in a mouse model of destructive arthritis. A
      sequence corresponding to amino acids 259-270 of CII was fused into the class II
      associated invariant chain peptide (CLIP) position of the invariant chain to
      achieve efficient binding to MHC II. Transduction of cloned cells and primary
      antigen-presenting cells (APCs) in vitro demonstrated successful presentation of
      the peptide on MHC II, and a physiological glycosylation pattern. Compared with
      controls, mice intravenously injected with lentiviral vectors encoding this
      epitope displayed significantly less frequent, less severe, and less destructive
      arthritis, decreased lymphocyte proliferation in response to restimulation with
      CII, and lower CII-specific antibody levels. This was associated with an
      increased production of transforming growth factor-beta (TGF-beta) in vitro. We
      suggest that overexpression of the immunodominant CII epitope on MHC II induces T
      cell production of TGF-beta and leads to inhibition of arthritis by means of both
      antigen-specific and bystander mechanisms. Thus, antigen-specific tolerance
      induction using lentiviral gene delivery can ameliorate arthritis.

PMID- 19174763
TI  - Cross-sectional, prospective study of MRI reproducibility in the assessment of
      plaque burden of the carotid arteries and aorta.
AB  - BACKGROUND: The reliability of imaging techniques to assess early atherosclerosis
      remains unclear. We did a cross-sectional, prospective study to test
      reproducibility of MRI when imaging arteries, to assess risk of cardiovascular
      disease and correlations with age and sex. METHODS: Between January 2003 and
      December 2006 we performed black-blood MRI of both common carotid arteries and
      the thoracic descending aorta in patients with cardiovascular risk factors who
      were referred from clinics in New York, NY, USA. Mean wall area, wall thickness,
      lumen area, total vessel area, and ratio of the mean wall area to the mean total
      vessel area (WA/TVA) were manually measured. Reproducibility within and between
      readers was tested on subsets of images from randomly chosen patients. RESULTS:
      MRI was performed on 300 patients. Intrareader reproducibility, assessed in
      images from 20 patients, was high for all parameters (intraclass correlation
      coefficients >0.8), except WA/TVA ratio in the descending aorta. The inter-reader
      reproducibility, assessed in images from 187 patients, was acceptable (intraclass
      correlation coefficients >0.7) for the mean wall, lumen, and total vessel areas.
      Values for all MRI parameters in all vessels increased with increasing age for
      both sexes (all P <0.0005) but were always significantly higher in men than in
      women, except for aortic mean wall thickness and WA/TVA ratio in the carotid
      arteries. Mean wall area values correlated well between the carotid arteries and
      aorta, reflecting the systemic nature of atherosclerosis. CONCLUSIONS: Our
      findings support MRI as a reproducible measurement of plaque burden and
      demonstrate the systemic distribution of atherosclerosis.

PMID- 19174764
TI  - Which fecal occult blood test is best to screen for colorectal cancer?
AB  - Fecal immunochemical tests (FITs) for hemoglobin represent a major advance over
      guaiac-based fecal occult blood tests (GFOBTs) for colorectal cancer screening.
      FITs specifically detect human hemoglobin in stool samples, whereas GFOBTs only
      detect heme. Studies show that FITs increase the detection rates of cancer and
      advanced adenoma compared with early-generation GFOBTs, and do so without the
      unacceptably high number of colonoscopies that high-sensitivity GFOBTs generate.
      Also, FITs are simpler to use than GFOBTs, they improve rates of patient
      participation, and their cut-off points for positive versus negative tests can be
      modified. A large, Dutch, population-based, randomized controlled trial has
      compared the performance of a GFOBT and a FIT on an intention-to-screen basis.
      This study found that the FIT detected two-and-a-half times as many cancers and
      advanced adenomas as did the GFOBT, despite similar colonoscopy rates. The latest
      generation of FITs should replace traditional GFOBTs in two-step (test then
      colonoscopy) screening for colorectal cancer.

PMID- 19174765
TI  - Is chromoendoscopy the new standard for cancer surveillance in patients with
      ulcerative colitis?
AB  - Chromoendoscopy was introduced in 2003 as a novel 'red flag' technique that aimed
      to increase the sensitivity of identifying flat, neoplastic lesions in patients
      with ulcerative colitis. The improved sensitivity of chromoendoscopy over
      standard white-light endoscopy has been confirmed in European and Asian centers.
      This commentary discusses the findings from a prospective, controlled study from
      the Mount Sinai Hospital in New York. The findings of this study provide
      unequivocal evidence that chromoendoscopy is superior to white-light endoscopy in
      the detection of neoplasias in patients with IBD. The authors of this study
      identified a greater number of lesions and a higher number of patients with
      dysplasia by use of this method and targeted biopsy sampling compared with
      standard endoscopy with random biopsy sampling. Chromoendoscopy in combination
      with targeted biopsies, therefore, has emerged as the new standard of cancer
      surveillance in patients with ulcerative colitis, and we can expect this
      technique to be incorporated into clinical guidelines shortly.

PMID- 19174766
TI  - Combining two imaging techniques is best to diagnose small-bowel Crohn's disease.
AB  - In most patients with Crohn's disease, diagnostic gastrointestinal lesions are
      located in the small bowel, which is not easily accessible to direct
      investigation. This commentary focuses on an article by Solem et al., which
      compared the utility of four primary small-bowel imaging modalities (CT
      enterography, ileocolonoscopy, capsule endoscopy, and small-bowel follow-through)
      in diagnosis of active small-bowel Crohn's disease. Capsule endoscopy had lower
      diagnostic specificity than the other techniques. This result, in conjunction
      with the need to perform preliminary small-bowel radiography to detect
      asymptomatic, partial, small-bowel obstructions, makes capsule endoscopy a poor
      choice as a first-line test for Crohn's disease. We concur with Solem et al.'s
      opinion that a combination of two of the other available imaging methods is the
      best diagnostic option for small-bowel Crohn's disease, although the choice of
      which two to use should be based on the facilities and expertise that are
      available locally.

PMID- 19174767
TI  - High-dose versus standard-dose PPI in triple therapy for Helicobacter pylori
      eradication.
AB  - Empiric clarithromycin-containing triple therapies for eradication of
      Helicobacter pylori do not reliably produce a >/=80% success rate on an intention
      to-treat basis. This lack of adequate treatment response is primarily because of
      clarithromycin resistance. This commentary discusses the findings of a meta
      analysis by Villoria et al. that investigated whether a triple therapy containing
      a high-dose PPI and clarithromycin plus either amoxicillin or tinidazole improves
      the success rate of H. pylori eradication compared with a triple therapy that
      contains a standard-dose PPI. The mean intention-to-treat cure rates were greater
      in patients who used the high-dose PPI regimen compared with the standard-dose
      regimen (82% vs 74%, respectively). However, the actual cure rates of these
      studies were poor and the improvements were unlikely to be clinically
      significant. The prevalence of clarithromycin resistance in most of the world is
      such that clarithromycin-containing triple therapy should not be used
      empirically. Alternatives include sequential or concomitant therapy and bismuth
      containing quadruple therapies.

PMID- 19174768
TI  - Transplant tourism: a growing phenomenon.
AB  - Medical tourism is increasing owing to high costs of care, lack of availability
      or long waits for procedures, and improvements in technology and standards of
      care in many countries. Transplant tourism is one example of medical tourism that
      has been attracting increasing attention because of concerns over poor treatment
      and outcomes of both donors and recipients. Most such cases involve vended
      kidneys obtained from vulnerable populations, and both donors and recipients
      receive inferior care by US standards. This commentary discusses a paper by Gill
      et al. that compared outcomes of 33 transplant tourists with those of patients
      transplanted at a US center. Fewer complications and better outcomes were seen in
      patients transplanted in the US center than among transplant tourists. Large
      transplant centers with long waiting times are increasingly likely to see
      patients return newly transplanted from overseas; such patients require urgent
      attention, with particular consideration to infectious complications.

PMID- 19174769
TI  - Can cardiac troponin T level be used to predict survival of patients awaiting
      renal transplantation?
AB  - Cardiac troponin T (cTnT) levels are often elevated in chronic kidney disease and
      correlate with survival of patients receiving dialysis. This commentary discusses
      a recent paper by Hickson et al. that investigated whether a single cTnT
      measurement can predict survival of patients on the waiting list for renal
      transplantation. Elevated cTnT levels (>0.01 ng/ml) were associated with left
      ventricular hypertrophy, reduced left ventricular ejection fraction and ischemia
      or resting ventricular wall motion abnormalities on dobutamine stress
      echocardiography, and also predicted mortality independently of age, diabetes or
      history of heart disease. Although the authors recommend intensive cardiac
      evaluation in patients with high cTnT levels on transplantation waiting lists,
      predicting who is at highest risk of dying on the waiting list has no practical
      utility unless an intervention can reliably lower that risk. Until then, the time
      patients spend on dialysis should be minimized by rapid referral for
      transplantation, prompt and appropriate waitlisting and widespread encouragement
      of living donation.

PMID- 19174770
TI  - Is peritoneal dialysis a suitable renal replacement therapy in autosomal dominant
      polycystic kidney disease?
AB  - This commentary discusses a study reported by Kumar et al. that compared outcomes
      of 56 patients with autosomal dominant polycystic kidney disease (ADPKD) started
      on peritoneal dialysis with those of a control group of nondiabetic patients
      matched for age, sex and year of starting peritoneal dialysis. During follow-up
      (mean 37 months), patient survival, technique survival and peritonitis rates were
      similar in the two groups. Peritoneal dialysis was not only possible but was also
      successful in 68% of patients. Although the study was well conducted and the
      results very encouraging, it did not address the relevant clinical issue of
      whether peritoneal dialysis is a less desirable option than hemodialysis in some
      patients with ADPKD, for example those with very large, cystic kidneys and/or a
      very large, cystic liver. Further studies to investigate renal replacement
      modalities in patients with ADPKD should relate study outcomes to the volumes of
      patients' kidneys and liver.

PMID- 19174771
TI  - An update on the use of mycophenolate mofetil in lupus nephritis and other
      primary glomerular diseases.
AB  - Mycophenolate mofetil (MMF) has been used successfully as an immunosuppressive
      medication in transplantation for over a decade. Owing to its efficacy and
      relatively benign adverse effect profile, its use has been investigated in the
      treatment of several glomerular diseases, as we describe in this Review. Of
      these, MMF has most extensively been studied in lupus nephritis. Randomized
      controlled trials have documented the value of MMF in both induction and
      maintenance therapy for severe lupus nephritis in several different geographic
      and ethnic populations, and have defined its potential toxicity. In minimal
      change disease, focal segmental glomerulosclerosis and membranous nephropathy,
      promising but limited data on MMF treatment exist from small retrospective and
      prospective studies. Ongoing, larger, prospective trials, such as the NIH trial
      in focal segmental glomerulosclerosis, might clarify the value of MMF in the
      treatment of this disease. The efficacy of MMF in IgA nephropathy remains
      unclear, despite several small, controlled trials. Conflicting results might
      reflect differences in the disease process, differences in MMF metabolism, or
      varying responses to the immunosuppressive agent in different populations. Only
      through large, collaborative, controlled trials will the true role of MMF be
      defined for each glomerular disease.

PMID- 19174772
TI  - A case of tuberous sclerosis complex that progressed to end-stage renal disease.
AB  - BACKGROUND: A 31-year-old woman with tuberous sclerosis complex presented with a
      1 week history of subjective fever, chills, rigors, poor appetite and dizziness.
      INVESTIGATIONS: Physical examination, urine and blood analysis, CT of the
      abdomen, chest and brain, and chest X-ray. DIAGNOSIS: End-stage renal disease,
      septic shock and urinary tract infection secondary to huge bilateral
      angiomyolipomas of the kidney associated with tuberous sclerosis complex.
      MANAGEMENT: Antibiotic therapy, vasopressor treatment and bilateral nephrectomy,
      followed by hemodialysis while awaiting renal transplantation.

PMID- 19174773
TI  - Putting ethics on the spot in neurology.

PMID- 19174774
TI  - Treatment for PSA screen-detected prostate cancer: what are the options?

PMID- 19174775
TI  - Unintended pregnancy during radiotherapy for cancer.
AB  - BACKGROUND: A 27-year-old woman with upper mediastinum stage IIA Hodgkin lymphoma
      was treated with six cycles of doxorubicin, bleomycin, vinblastine, and
      dacarbazine chemotherapy. Two months later she received a total of 4,250 cGy to
      the upper mediastinum and left clavicular region over a 1-month period. One week
      after completion of radiotherapy she was found to be 13-weeks pregnant. Her
      physician advised her to terminate pregnancy. She contacted a teratology
      information service for further information regarding the risks of radiation
      exposure for her fetus. INVESTIGATIONS: Estimation of fetal radiation exposure,
      literature review and synthesis of published cases and effects of fetal radiation
      exposure. DIAGNOSIS: Estimated fetal radiation dose between 5 and 18 cGy.
      MANAGEMENT: Counseling on the possible risks to the fetus as a result of
      radiation exposure.

PMID- 19174776
TI  - Xoft Axxent electronic brachytherapy: a new device for delivering brachytherapy
      to the breast.
AB  - Balloon-based brachytherapy was developed to simplify the brachytherapy technique
      and make accelerated partial breast irradiation more accessible to patients with
      breast cancer who are suitable candidates for this technique. Xoft Axxent (Xoft,
      Inc., Sunnyvale, CA) electronic brachytherapy is a novel method of accelerated
      partial breast irradiation that uses an electronic source to produce X-rays. Xoft
      Axxent treatment does not require a high-dose-rate afterloader unit or a shielded
      vault, unlike other brachytherapy techniques that use iridium-192, such as
      MammoSite brachytherapy. Xoft Axxent is associated with the delivery of less
      radiation to normal tissues, and increased high radiation dose regions or 'hot
      spots' to the target volume compared with treatment with the MammoSite device.
      Further research will be needed to determine subgroups of patients who might
      benefit from treatment with Xoft Axxent electronic brachytherapy.

PMID- 19174777
TI  - Pharmacogenomic progress in individualized dosing of key drugs for cancer
      patients.
AB  - Determining the correct dosage for the majority of traditional chemotherapeutic
      agents presents a challenge because most drugs have a narrow therapeutic index,
      which results in a fine balance between doses that cause significant drug
      toxicity and loss of efficacy. Dosing calculations for most agents use the
      patient's body surface area, a method that correlates poorly with drug
      pharmacokinetics. Genetic differences in drug-metabolizing enzymes are being
      evaluated in an effort to explain the pharmacokinetic and pharmacodynamic
      variability seen with many chemotherapeutic agents. Elucidation of the underlying
      reasons for this variability will enable individualization of therapy to minimize
      toxicity and maximize efficacy, and thus improve control over the narrow
      therapeutic index of these agents. Such investigations have led to Clinical
      Pharmacology FDA Subcommittee recommendations for changes to drug package
      instructions. This Review discusses the current limitations of body-surface-area
      based dosing, examples of successful pharmacogenomic investigations that have
      used drug-metabolizing enzymes to decrease drug toxicity and/or improve efficacy,
      and the future promises of pharmacogenomic-directed pharmacotherapy.

PMID- 19174778
TI  - Role of interleukin-6 in human nonalcoholic steatohepatitis. Response to Dogru et
      al.

PMID- 19174779
TI  - Endoscopic sphincterotomy combined with large balloon dilation can reduce the
      procedure time and fluoroscopy time for removal of large bile duct stones.
AB  - OBJECTIVES: We sought to evaluate the safety, efficacy, and feasibility of
      endoscopic sphincterotomy plus large balloon dilation (ESLBD) and to compare
      procedural time and fluoroscopy time of ESLBD with those of endoscopic
      sphincterotomy (EST) alone for patients with large bile duct stones. METHODS:
      Retrospective analysis. RESULTS: A total of 101 patients with large bile duct
      stones were treated: 53 were treated by ESLBD and 48 with EST alone. ESLBD
      resulted in similar outcomes in overall successful stone removal (100% vs. 97%)
      and complications (4% vs. 6%); however, although the rate of complete stone
      removal in the first session using ESLBD tended to be higher than when EST alone
      was used, it was not statistically significant (96% vs. 85%, P=0.057). Mechanical
      lithotripsy was required significantly more often in the EST group compared to
      the ESLBD group (25% vs. 6%, P<0.01). Total procedure time in the ESLBD group was
      significantly shorter than that of the EST group (32 vs. 40 min, P<0.05). Total
      fluoroscopy time in the ESLBD group was significantly shorter in the EST group
      (13 vs. 22 min, P<0.05). CONCLUSIONS: ESLBD is an effective and safe treatment in
      patients with large bile duct stones. In addition, ESLBD appears to decrease
      procedure time and fluoroscopy time and reduce the need for mechanical
      lithotripsy as compared to EST alone.

PMID- 19174780
TI  - Confirmation of multiple Crohn's disease susceptibility loci in a large Dutch
      Belgian cohort.
AB  - OBJECTIVES: Inflammatory bowel diseases (IBD)-Crohn's disease (CD) and ulcerative
      colitis (UC)-are chronic gastrointestinal inflammatory disorders with a complex
      genetic background. A genome-wide association scan by the Wellcome Trust Case
      Control Consortium (WTCCC) recently identified several novel susceptibility loci.
      METHODS: We performed a large replication study in 2,731 Dutch and Belgian IBD
      patients (1,656 CD and 1,075 UC) and 1,086 controls. In total, 40 single
      nucleotide polymorphisms (SNPs) that showed moderate or strong association in the
      WTCCC study, along with SNPs in the previously identified genes IL23R, ATG16L1,
      and NELL1, were studied. RESULTS: We confirmed the associations with IL23R
      (rs11209026, P=2.69E-12), ATG16L1 (rs2241880, P=4.82E-07), IRGM (rs4958847,
      P=2.26E-05), NKX2-3 (rs10883365, P=5.91E-06), 1q24 (rs12035082, P=1.51E-05), 5p13
      (rs17234657, P=2.62E-05), and 10q21 (rs10761659, P=8.95E-04). We also identified
      associations with cyclin Y (CCNY; rs3936503, P=2.09 E-04) and Hect domain and
      RCC1-like domain 2 (HERC2; rs916977, P=1.12E-04). Pooling our data with the
      original WTCCC data substantiated these associations. Several SNPs were also
      moderately associated with UC. Two genetic risk profiles based on the number of
      risk alleles and based on a weighted score were created. On the basis of these
      results, we calculated sensitivities, specificities, positive and negative
      predictive values, and likelihood ratios for CD. CONCLUSIONS: We replicated
      genetic associations for CD with IL23R, ATG16L1, IRGM, NKX2-3, 1q24, 10q21, 5p13,
      and PTPN2 and report evidence for associations with HERC2 and CCNY. Pooling our
      data with the results of the WTCCC strengthened the results, suggesting genuine
      genetic associations. We show that a genetic risk profile can be constructed that
      is clinically useful and that can aid in making treatment decisions.

PMID- 19174781
TI  - Loss of response and requirement of infliximab dose intensification in Crohn's
      disease: a review.
AB  - OBJECTIVES: To review the frequency with which infliximabloses its effect and
      dose "intensification" is required for Crohn's disease treatment. METHODS:
      Bibliographical searches were performed in MEDLINE, and European (ECCO) and
      American (DDW) Congresses. Studies evaluating loss of efficacy and requirement of
      infliximab dose intensification-defined either as an increase of the infliximab
      dose (generally from 5 mg/kg to 10 mg/kg) or as a decrease in the frequency of
      infusion (to as often as every 4 weeks)-in Crohn's disease patients were
      included. RESULTS: Sixteen studies evaluating the incidence of loss of response
      to infliximab in Crohn's disease patients were found. A total of 2,236 patients
      were included (the majority of them receiving a three-dose induction regimen at
      weeks 0, 2, and 6, followed by maintenance therapy every 8 weeks), providing
      6,284 patient-years of follow-up. The mean percentage of patients with loss of
      infliximab response was 37%. However, as the follow-up time varied markedly among
      studies, the risk of losing response to infliximab is better expressed as the
      incidence of this complication per patient-year of follow-up. Therefore, the
      annual risk for loss of infliximab response was calculated to be 13% per patient
      year. CONCLUSIONS: A variable but relevant proportion of Crohn's disease patients
      on long-term infliximab treatment lose response. This may be interpreted in two
      different but compatible ways: a positive view, highlighting that infliximab
      therapy is relatively durable, with the majority of patients predicted to
      continue infliximab treatment at least during the first year; or a negative view,
      interpreting that a significant proportion of Crohn's disease patients-more than
      10% per patient-year of infliximab treatment-on long term will lose response and
      will require an increase in dose and/or decrease in infusion interval.

PMID- 19174782
TI  - How common is diclofenac-associated liver injury? Analysis of 17,289 arthritis
      patients in a long-term prospective clinical trial.
AB  - OBJECTIVES: Few data are available from prospective trials to define the
      hepatotoxicity of diclofenac, the most widely prescribed non-steroidal anti
      inflammatory drug (NSAID) in the world. We determined the rate of laboratory and
      clinical adverse hepatic effects in a large double-blind trial of diclofenac.
      METHODS: Patients > or = 50 years with rheumatoid arthritis or osteoarthritis
      were randomly assigned to diclofenac (150 mg daily) or etoricoxib (60 or 90 mg
      daily). Patients with hepatic disease or who reported > or = 14 alcoholic drinks
      weekly were excluded. Patients had visits (with liver tests) every 4 months and
      were contacted by phone between visits and every 6 months after discontinuation
      until the end of the study. Causality assessment was performed for liver-related
      hospitalizations, Hy's cases (serious adverse events with AST or ALT >3 x upper
      limit of normal (ULN) and bilirubin >2 xULN), and liver failure/transplant/death.
      RESULTS: A total of 17,289 patients received diclofenac for a mean of 18 months.
      Liver end points with diclofenac were ALT/AST>3 xULN: 527(3.1%); ALT/AST >10
      xULN: 86(0.5%); liver-related hospitalizations: 4(0.023%); Hy's cases: 2(0.012%);
      liver failure/death/transplant: 0. Aminotransferase elevations occurred primarily
      within the first 4-6 months of therapy, whereas liver-related hospitalizations
      occurred between 9 days and 21 months. CONCLUSIONS: Diclofenac is commonly
      associated with aminotransferase elevations, generally in the first 4-6 months of
      therapy. Clinical liver events requiring hospitalization are relatively rare
      (23/100,000 patients), but may develop early or late in therapy. The markedly
      increased rate of aminotransferase elevation with diclofenac may not be
      paralleled by a proportional marked increase in clinical liver events, although
      clinical events potentially also may be decreased with regular monitoring in a
      clinical trial setting.

PMID- 19174783
TI  - Circumferential and focal ablation of Barrett's esophagus containing dysplasia.
AB  - OBJECTIVES: Dysplasia in a Barrett's esophagus (BE) is associated with an
      increased risk for developing esophageal adenocarcinoma. Ablation using the HALO
      system has shown promise for the treatment of BE with dysplasia. The objective of
      this study was to assess the safety and efficacy of a stepwise regimen of
      circumferential and focal ablation using the HALO system for the treatment of BE
      with dysplasia. METHODS: BE patients with low-grade dysplasia (LGD) or high-grade
      dysplasia (HGD) were enrolled. Primary circumferential ablation was followed
      every 3 months by further circumferential ablation or focal ablation until
      complete endoscopic eradication of BE was achieved. At 3- or 6-month intervals,
      depending on baseline grade, targeted and four quadrant random biopsies were
      obtained to assess the histological response to ablation. A complete response
      (CR) is defined as all biopsies negative for intestinal metaplasia (IM) (CR-IM)
      or dysplasia (CR-D) at last available follow-up. RESULTS: A total of 63 patients
      were treated (57 men; median age 71 years; median BE length 5 cm), with worst
      grade of dysplasia being LGD (n=39) and HGD (n=24). Follow-up is available for 62
      patients (median 24 months). Overall, CR-IM is 79% and CR-D is 89%. For the LGD
      cohort, CR-IM is 87% and CR-D is 95%. For the HGD cohort, CR-IM is 67% and CR-D
      is 79%. CONCLUSIONS: Stepwise circumferential and focal ablation of BE containing
      dysplasia appears to be a safe and effective intervention, achieving a CR for
      dysplasia in 95% and 79% of LGD and HGD patients, respectively.

PMID- 19174784
TI  - Expression of bile acid transporting proteins in Barrett's esophagus and
      esophageal adenocarcinoma.
AB  - OBJECTIVES: Barrett's esophagus (BE) is a metaplastic lesion characterized by
      replacement of the normal squamous epithelium by columnar intestinal epithelium
      containing goblet cells. It is speculated that this process is an adaptation to
      protect cells from components of refluxate, such as gastric acid and bile acids.
      In contrast to the normal squamous epithelium, enterocytes of the distal ileum
      are adapted to transport bile acids from the intestinal lumen. Several bile acid
      transporters are utilized for effective removal of bile acids, including the
      apical sodium-dependent bile acid transporter (ASBT), the ileal bile acid-binding
      protein (IBABP), and the multidrug-resistant protein 3 (MRP3). We hypothesized
      that one of the possible functions of newly arising metaplastic epithelium, in
      the esophagus, is to transport bile acids. Our major goal was to evaluate the
      expression of bile acid transporters in normal squamous epithelium, BE with
      different grades of dysplasia, and esophageal adenocarcinoma (EAC). METHODS: A
      total of 101 patients were included in this study. Immunohistochemistry (IHC) and
      reverse transcriptase (RT)-PCR were used to detect the expression of these
      transporters at the mRNA and protein levels. RESULTS: Our immunohistochemical
      studies showed that all three bile acid transporters are expressed in BE glands,
      but not in squamous epithelium. ASBT was found in the apical border in BE
      biopsies. The highest frequency of ASBT expression was in patients with
      nondysplastic BE (9 of 15, 60%), and a progressive loss of ASBT was observed
      through the stages of dysplasia. ASBT was not detected in EAC (0 of 15). IBABP
      staining was observed in the cytoplasm of BE epithelial surface cells. Expression
      of IBABP was found in 100% of nondysplastic BE (14 of 14), in 93% of low-grade
      dysplasia (LGD, 15 of 16), in 73% of high-grade dysplasia (HGD, 10 of 14), and in
      33% of EAC (5 of 15). MRP3 was expressed in the basolateral membrane in 93% of
      nondysplastic BE (13 of 14), in 60% of LGD (10 of 16), and in 86% of HGD (11 of
      13). Only weak MRP3 staining was detected in EAC biopsies (5 of 15, 33%). In
      addition, RT-PCR studies showed increased expression of mRNA coding for ASBT
      (6.1x), IBABP (9.1x), and MRP3 (2.4x) in BE (N=13) compared with normal squamous
      epithelium (N=15). Significantly increased mRNA levels of IBABP (10.1x) and MRP3
      (2.5x) were also detected in EAC (N=21) compared with normal squamous epithelium.
      CONCLUSIONS: We found that bile acid transporters expression is increased in BE
      tissue at the mRNA and protein levels and that expression of bile acid
      transporter proteins decreased with progression to cancer.

PMID- 19174785
TI  - RUNX3 inactivation in colorectal polyps arising through different pathways of
      colonic carcinogenesis.
AB  - OBJECTIVES: We hypothesized that RUNX3 inactivation by promoter hypermethylation
      in colorectal polyps is an early molecular event in colorectal carcinogenesis.
      METHODS: RUNX3 protein expression was analyzed immunohistochemically in 50
      sporadic colorectal polyps comprising 19 hyperplastic polyps (HPs), 14
      traditional serrated adenomas (TSAs), and 17 sporadic traditional adenomas (sTAs)
      as well as in 19 familial adenomatous polyposis (FAP) samples from 10 patients
      showing aberrant crypt foci (ACF) (n=91), small adenomas (SmAds) (n=40), and
      large adenomas (LAds) (n=13). In addition, we assessed the frequency of promoter
      hypermethylation of RUNX3 by methylation-specific PCR (MSP) in all the 50
      sporadic polyps as well as 38 microdissected FAP polyps comprising ACF, SmAds,
      and LAds obtained from 7 FAP samples. A total of 12 normal colon samples were
      also included for RUNX3 MSP analysis. RESULTS: Compared to normal colon (2 of 12,
      16%) and sTAs (3 of 17, 18%), HPs (15 of 19, 79%) and TSAs (8 of 14, 57%)
      displayed significant inactivation of RUNX3 (P<0.05). In FAP, RUNX3 inactivation
      was more frequently seen in ACF (78 of 91, 86%), SmAds (25 of 40, 62%), and LAds
      (6 of 13, 46%) compared to normal mucosa (0 of 19, 0%) in the same samples (all
      P<0.05). Promoter hypermethylation of RUNX3 was significantly higher in
      colorectal polyps (64 of 87, 74%) compared to normal colon (2 of 12, 16%)
      (P=0.001). Serrated polyps such as HPs (17 of 19, 89%) and TSAs (12 of 14, 86%)
      were significantly more methylated than sTAs (7 of 17, 44%) (P=0.004). RUNX3
      hypermethylation was observed in 28 of the total 38 (74%) FAP polyps. Overall,
      RUNX3 promoter methylation correlated with inactivation of RUNX3 expression in
      sporadic (27 of 36, 75%) (P=0.022) and FAP (21 of 28, 75%) (P=0.021) polyps.
      CONCLUSIONS: Our data suggest that RUNX3 inactivation due to promoter
      hypermethylation in colorectal polyps represents an early event in colorectal
      cancer (CRC) progression. In addition, epigenetic RUNX3 inactivation is a
      frequent event in the serrated colonic polyps as well as in the ACF of FAP
      polyps.

PMID- 19174787
TI  - Influence of phenotype at diagnosis and of other potential prognostic factors on
      the course of inflammatory bowel disease.
AB  - OBJECTIVES: Disease course in inflammatory bowel disease (IBD) is variable and
      difficult to predict. To optimize prognosis, it is of interest to identify
      phenotypic characteristics at disease onset and other prognostic factors that
      predict disease course. The aim of this study was to evaluate such factors in a
      population-based IBD group. METHODS: IBD patients diagnosed between 1 January
      1991 and 1 January 2003 were included. A follow-up questionnaire was developed
      and medical records were reviewed. Patients were classified according to
      phenotype at diagnosis and risk factors were registered. Disease severity,
      cumulative medication use, and "surgical" and "nonsurgical" recurrence rates were
      calculated as outcome parameters. RESULTS: In total, 476 Crohn's disease (CD),
      630 ulcerative colitis (UC), and 81 indeterminate colitis (IC) patients were
      diagnosed. In CD (mean follow-up 7.6 years), 50% had undergone resective surgery.
      In UC (mean follow-up 7 years), colectomy rate was 8.3%. First year cumulative
      recurrence rates per 100 patient-years for CD, UC, and IC were 53, 44, and 42%,
      respectively. In CD, small bowel localization and stricturing disease were
      negative prognostic factors for surgery, as was young age. Overall recurrence
      rate was increased by young age and current smoking. In UC, extensive colitis
      increased surgical risk. In UC, older age at diagnosis initially increased
      recurrence risk but was subsequently protective. CONCLUSIONS: This population
      based IBD study showed high recurrence rates in the first year. In CD, small
      bowel localization, stricturing disease, and young age were predictive for
      disease recurrence. In UC, extensive colitis and older age at diagnosis were
      negative prognostic predictors.

PMID- 19174786
TI  - Immune response to influenza vaccine in children with inflammatory bowel disease.
AB  - OBJECTIVES: Patients with inflammatory bowel disease (IBD) frequently receive
      immunosuppressive therapy. The immune response in these patients to vaccines has
      not been well studied. We conducted a prospective, open label study to evaluate
      the serologic response to influenza vaccine in children with IBD. METHODS: Serum
      was obtained from 146 children and young adults with IBD (96 Crohn's disease, 47
      ulcerative colitis, and 3 indeterminate colitis) for baseline influenza titer,
      immediately followed by immunization with trivalent (A/Solomon Islands/3/2006
      (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 (B)) inactivated
      influenza vaccine. Patients returned for repeat titers 3-9 weeks later.
      Seroprotection against each influenza strain was defined as hemagglutination
      inhibition titer > or = 40. Patients were categorized as nonimmunosuppressed
      (NIS; aminosalicylates only, antibiotics only, or no therapy) or immunosuppressed
      (IS; any immunosuppressive agent). IS patients were further subcategorized as:
      (i) tacrolimus, (ii) tumor necrosis factor-alpha (TNF-alpha) inhibitor, (3)
      immunomodulator, and (4) corticosteroids only. RESULTS: More patients were
      seroprotected against strains A/H1N1 and A/H3N2 than B strain (P<0.02),
      regardless of immunosuppression status. The proportion of seroprotected patients
      and geometric mean titers at post-vaccination were similar between NIS and IS
      groups for all three strains. Subanalysis of patients not seroprotected at
      baseline showed that those receiving anti-TNF therapy were less likely to be
      seroprotected against strain B (14%) compared to patients in the NIS group (39%,
      P=0.025). There were no serious vaccine-associated adverse events. CONCLUSIONS:
      Influenza vaccination produces a high prevalence of seroprotection in IBD
      patients, particularly against A strains. The vaccine is well tolerated. Routine
      influenza vaccination in IBD patients is recommended, irrespective of whether
      patients receive immunosuppressive medications.

PMID- 19174788
TI  - Dissecting GI phenotype-genotype relationships in GERD and dyspepsia: an SNP here
      and an SNP there!
AB  - It is known that the predisposition to human disease is a mixture of inherited
      susceptibility and acquired exposure to environmental factors. Understanding
      gastrointestinal disease has indicated that germline adenomatous polyposis coli
      mutations predispose with a 99% certainty to colorectal cancer, whereas squamous
      esophageal cancer is caused by a combination of environmental exposures
      (including alcohol consumption, cigarette smoke, ingestion of contaminated
      preserved food) and/or infection (specifically with human papilloma virus), in
      most cases. Until now, despite the reasonably strong evidence for genetic risk
      from monozygotic twin studies for gastro-esophageal reflux disease (GERD), there
      have been no documented genetic targets in GERD. In this edition of the Journal,
      there is intriguing evidence that a common, single base-pair change in the
      secondary messenger gene GNbeta3 (i.e., a single-nucleotide polymorphism) may be
      important, perhaps through promoting abnormal perception of visceral pain in the
      esophagus. Other works link this genetic factor to functional dyspepsia, and
      these exciting preliminary lines of evidence are reviewed.

PMID- 19174790
TI  - Parvovirus B19 infection and immunosuppressed IBD-affected pediatricians.

PMID- 19174789
TI  - Hyperdynamic upper esophageal sphincter pressure: a manometric observation in
      patients reporting globus sensation.
AB  - OBJECTIVES: Although globus sensation is a common symptom, its pathogenesis is
      poorly defined. The aim of this study was to quantify the timing and magnitude of
      respiratory variation in upper esophageal sphincter (UES) pressure with high
      resolution manometry (HRM) in patients with globus sensation, normal controls,
      and gastroesophageal reflux disease (GERD) patients without globus sensation.
      METHODS: HRM recordings spanning from the hypopharynx to the stomach were
      analyzed in 131 consecutive globus patients with normal (64) and abnormal (67)
      distal esophageal motility. Resting UES pressure was analyzed up to 5 min before
      10 5-ml water swallows. Change in UES pressure, its average magnitude between
      inspiration and expiration, and nadir UES relaxation pressure in globus patients
      were compared with those in 68 controls and 46 GERD patients without globus.
      RESULTS: UES pressure typically increased during inspiration in both controls and
      patients. Respiration-related change in resting UES pressure was significantly
      amplified in globus patients (37.3 mm Hg) compared with controls (10.6 mm Hg) and
      GERD patients (13.0 mm Hg) (P<0.0001). A respiratory change in UES pressure>27 mm
      Hg was found in >60% of globus patients and <15% of controls and GERD patients
      without globus. This hyperdynamic UES was not associated with other abnormalities
      of esophageal motor function. CONCLUSIONS: Hyperdynamic respiratory UES pressure
      changes were prevalent in patients reporting globus sensation irrespective of
      their deglutitive UES and distal esophageal motility. Although the etiology of
      this hyperdynamic UES is unclear, it does appear to be a frequent manometric
      observation in this patient group and may provide a new focus for further studies
      into pathogenesis and therapy.

PMID- 19174791
TI  - Neuroimmune interaction and anorectal motility in children with food allergy
      related chronic constipation.
AB  - OBJECTIVES: Food allergy is thought to trigger functional constipation in
      children but the underlying mechanisms are still unknown. Mast cells (MCs) and
      their relationship with nerve fibers (NFs) in the rectal mucosa, as well as
      anorectal motility, were studied in children with refractory chronic constipation
      before and after an elimination diet for cow's milk, egg, and soy proteins.
      METHODS: Thirty-three children (range: 1-10.8 years) underwent anorectal
      manometry and suction rectal biopsy before and after 8 weeks of oligoantigenic
      diet. MCs and NFs were identified immunohistochemically. Quantification of MCs
      (%MC/area) and MCs within 10 microm of NFs (%MC-NF/area) was performed by
      computer-assisted analysis. RESULTS: Eighteen children responded to the diet (R
      group) and fifteen did not (the NR-group). At baseline there was a significant
      difference in anal resting pressure (ARP; mm Hg), percentage of relaxation (%R),
      and residual pressure (RP; mm Hg) of anal canal during rectal distension between
      the R-group (66+/-4.1, 84.3+/-2.8, 10.4+/-2.3, respectively) and the NR-group
      (49+/-5, 92.2+/-1.7, 4.8+/-1.7, respectively; P<0.05). After the diet,
      significant changes in ARP, RP, and %R were observed only in the R-group (44+/
      3.7, 93.7+/-1.5, 3.8+/-1.2, respectively; P<0.05). At baseline, the R-group
      showed an increase in %MC/area (8.3+/-0.7) and %MC-NF/area (5.2+/-2.6) with
      respect to the NR-group (5.1+/-0.5 and 2.3+/-0.4, respectively; P<0.05). After
      the diet, only the R-group showed a significant reduction of %MC/area and %MC
      NF/area (4.4+/-0.5 and 2.2+/-0.4, respectively; P<0.001). Both ARP and RP
      significantly correlated with %MC/area and %MC-NF/area; %R showed a significant
      inverse correlation with both %MC/area and %MC-NF/area. CONCLUSIONS: In children
      with food allergy-related chronic constipation, an increase in both rectal MC
      density and spatial interactions between MCs and NFs correlates with anal motor
      abnormalities. These variables are significantly affected by the diet.

PMID- 19174792
TI  - Effect of a probiotic preparation (VSL#3) on induction and maintenance of
      remission in children with ulcerative colitis.
AB  - OBJECTIVES: Several probiotic compounds have shown promise in the therapy of
      ulcerative colitis (UC). However, a strong sustained benefit remains to be seen.
      Uncontrolled pilot studies suggest that a probiotic preparation (VSL#3) maintains
      remission in mild to moderate UC and reduces active inflammation in adult
      patients. Aims of our prospective, 1-year, placebo-controlled, double-blind study
      were to assess the efficacy of VSL#3 on induction and maintenance of remission
      and to evaluate the safety and tolerability of the probiotic preparation therapy
      in children with active UC. METHODS: A total of 29 consecutive patients (mean
      age: 9.8 years; range: 1.7-16.1 years; female/male: 13/16) with newly diagnosed
      UC were randomized to receive either VSL#3 (weight-based dose, range: 450-1,800
      billion bacteria/day; n=14) or an identical placebo (n=15) in conjunction with
      concomitant steroid induction and mesalamine maintenance treatment. Children were
      prospectively evaluated at four time points: within 1 month, 2 months, 6 months,
      and 1 year after diagnosis or at the time of relapse. Lichtiger colitis activity
      index and a physician's global assessment were used to measure disease activity.
      At baseline, within 6 months and 12 months or at the time of relapse, all
      patients were assessed endoscopically and histologically. RESULTS: All 29
      patients responded to the inflammatory bowel disease (IBD) induction therapy.
      Remission was achieved in 13 patients (92.8%) treated with VSL#3 and IBD therapy
      and in 4 patients (36.4%) treated with placebo and IBD therapy (P<0.001).
      Overall, 3 of 14 (21.4%) patients treated with VSL#3 and IBD therapy and 11 of 15
      (73.3%) patients treated with placebo and IBD therapy relapsed within 1 year of
      follow-up (P=0.014; RR=0.32; CI=0.025-0.773; NNT=2). All 3 patients treated with
      VSL#3 and 6 of 11 (54.5%) patients treated with placebo relapsed within 6 months
      of diagnosis. At 6 months, 12 months, or at time of relapse, endoscopic and
      histological scores were significantly lower in the VSL#3 group than in the
      placebo group (P<0.05). There were no biochemical or clinical adverse events
      related to VSL#3. CONCLUSIONS: This is the first pediatric, randomized, placebo
      controlled trial that suggests the efficacy and safety of a highly concentrated
      mixture of probiotic bacterial strains (VSL#3) in active UC and demonstrates its
      role in maintenance of remission.

PMID- 19174793
TI  - Gastroesophageal reflux disease is associated with the C825T polymorphism in the
      G-protein beta3 subunit gene (GNB3).
AB  - OBJECTIVES: Visceral hypersensitivity is involved in the etiology of reflux
      symptoms. Familial clustering and twin studies demonstrated a genetic
      predisposition to gastroesophageal reflux disease (GERD). G-protein-coupled
      receptors (GPCRs) mediate the response to acid, neurotransmitters and humoral
      factors modulating esophageal sensory function. Thus, polymorphisms in G-proteins
      are putative genetic factors contributing to GERD manifestation. A functional
      polymorphism in the G-protein beta3 subunit gene (GNB3) is associated with
      functional dyspepsia (FD), in which visceral hypersensitivity is implicated in
      symptom generation. We evaluated the association of the GNB3 C825T polymorphism
      with GERD and GERD subgroups classified according to esophageal acid exposure
      time, symptom-reflux correlation, or coexistence of FD and/or irritable bowel
      syndrome (IBS) symptoms. METHODS: In total, 363 GERD patients, defined as having
      esophageal pH < 4 > or = 6% of time and/or symptom index (SI) > or = 50% or
      symptom association probability (SAP) > or = 95%, participated. In addition, 373
      healthy controls free of gastrointestinal symptoms were studied. Genotyping was
      performed by molecular beacon assay. RESULTS: The CT genotype was more prevalent
      in GERD patients relative to healthy controls (adjusted odds ratio (OR)=1.43, 95%
      CI 1.04-1.98). GERD patients sensitive to physiological amounts of reflux
      displayed a higher OR (1.59), as did GERD patients with a positive symptom
      association score (1.50). The strongest association was detected in patients
      without concomitant FD and/or IBS symptoms (OR=1.66). CONCLUSIONS: GERD is
      associated with GNB3 C825T. The results for GERD subgroups support the hypothesis
      that enhanced perception of reflux events, as a consequence of the increased
      signal transduction upon GPCR activation associated with the 825T allele,
      underlies this association.

PMID- 19174794
TI  - Importance of gender, socioeconomic status, and history of abuse on patient
      preference for endoscopist.
AB  - OBJECTIVES: Patients have previously expressed preference for the gender of their
      endoscopist. Most of these patients were Caucasian women of predominantly high
      socioeconomic status. No study has evaluated the gender preferences of both women
      and men from a diverse but predominantly low socioeconomic background. The aim of
      this study was to evaluate gender preferences for endoscopists within an inner
      city, tertiary care population. METHODS: Consecutive patients scheduled for
      elective outpatient upper or lower endoscopy were prospectively asked to complete
      a questionnaire. Data included patient demographics, income level, education
      level, medical history, social history, abuse history, and gender preferences
      toward various health-care professionals. RESULTS: A total of 500 patients
      completed the study (286 women, 214 men). Overall, 33% of patients surveyed had a
      preference for the gender of their endoscopist (165/500; CI: 29-37%). Women were
      significantly more likely to have a gender preference vs. men (42.3 vs. 21%;
      P<0.001). Female gender, lower income level, and history of physical/emotional
      abuse were significant factors for gender preference, as shown by multivariate
      analysis. Of our patients, 88 (18%) reported a history of abuse. A history of
      abuse significantly increased the percentage of patients with a gender preference
      for endoscopist (P<0.001). CONCLUSIONS: Women in our inner-city tertiary care
      center expressed gender preference for their endoscopist at rates similar to
      those seen in previous studies. A higher percentage of men had a gender
      preference than previously reported. Both men and women with a history of abuse
      are significantly more likely to prefer a woman endoscopist. Physicians should be
      aware of these high preference rates to increase compliance and optimize patient
      care.

PMID- 19174795
TI  - Elevated human beta-defensin-2 levels indicate an activation of the innate immune
      system in patients with irritable bowel syndrome.
AB  - OBJECTIVES: Irritable bowel syndrome (IBS) is a highly prevalent functional
      disorder. According to the Rome criteria, macroscopic and histological
      inflammation is a crucial exclusion criterion for IBS. Human defensins appear to
      be part of the innate immune system in the gastrointestinal tract. Human beta
      defensin-2 (HBD-2) was the first inducible human antimicrobial protein
      discovered. The expression is induced by probiotic microorganisms and
      proinflammatory cytokines. Recent results imply that HBD-2 is expressed in active
      intestinal inflammation, especially in ulcerative colitis (UC). Our aim was to
      evaluate fecal measurements of HBD-2 in patients with active UC and IBS, and in
      healthy controls (HCs). METHODS: Fecal specimens were collected from a total of
      100 participants (30 with active UC, 46 IBS, and 24 HCs). Exclusion criteria were
      the current use of probiotics and antibiotics. Furthermore, IBS patients with
      elevated C-reactive protein or leukocytes, a history of bacterial overgrowth or
      infectious gastrointestinal disease over the last 6 month were excluded. Disease
      status was addressed in all participating subjects by medical history and current
      symptoms. In addition, each IBS and UC patient underwent ileocolonoscopy with
      histopathology. Fecal inflammation markers lactoferrin (Lf) and calprotectin
      (Cal) were measured by enzyme-linked immunosorbent assay (ELISA) and reported as
      microg/g. Fecal HBD-2 was measured by ELISA and reported as ng/g feces. In
      addition, immunoblots were performed for fecal HBD-2. Paraffin-embedded tissue
      from colonic biopsies was tested for HBD-2 peptides by immunohistochemistry.
      RESULTS: Lf as well as Cal was elevated in active UC (mean: 152.1+/-s.d. 374.7
      microg/g; 103.5+/-87.1 microg/g), compared with IBS (8.3+/-19.4 microg/g; 18.6+/
      23.3 microg/g), and HCs (0.4+/-0.5 microg/g; 7.1+/-7.9 microg/g). Scheffe post
      hoc tests revealed significant differences (P=0.006; P<0.001) between active UC
      vs. IBS and HC. In contrast, HBD-2 levels were highest in active UC (mean:
      106.9+/-s.d. 91.5 ng/g), almost as high in IBS (pts 76.0+/-67.9 ng/g), and lowest
      for HCs (29.9+/-16.1 ng/g). Scheffe post hoc tests revealed significant
      differences (P<0.001) between the groups of patients (UC and IBS) vs. HCs.
      Immunohistochemical investigation was consistent with fecal secretion data and
      demonstrated the presence of beta-defensin 2 peptides in colonic epithelial
      enterocytes in UC as well as IBS patients with elevated fecal HBD-2. CONCLUSIONS:
      The results indicate significantly elevated levels of HBD-2 in patients with IBS
      compared with HCs and similar to those with active UC. The results support an
      activation of the mucosal innate defense system toward a proinflammatory response
      in IBS patients in the absence of macroscopic signs of inflammation.

PMID- 19174796
TI  - Parotitis during oral double-balloon enteroscopy: an unexpected but benign
      finding.

PMID- 19174797
TI  - Mucosal immune activation in irritable bowel syndrome: gender-dependence and
      association with digestive symptoms.
AB  - OBJECTIVES: Immune activation may be involved in the pathogenesis of irritable
      bowel syndrome (IBS). However, the relative magnitude of this immune component
      and its correlation with gender and gastrointestinal complaints in IBS patients
      remains poorly elucidated. METHODS: We enrolled 48 IBS patients, with either
      diarrhea or constipation, 12 patients with microscopic colitis, 20 patients with
      ulcerative colitis, and 24 healthy controls. Colonic immunocytes were identified
      with quantitative immunohistochemistry on mucosal biopsies. Gastrointestinal
      symptoms were assessed using a validated questionnaire. RESULTS: IBS patients
      showed a significant 72% increase in mucosal immune cells compared to controls
      (P<0.001). Further analyses showed that increased immune cells were present in
      50% of the IBS patients. The magnitude of the immune infiltrate in IBS was
      significantly lower than that of microscopic colitis or ulcerative colitis (42%
      and 124% increases vs. IBS, respectively; P<0.001). Compared with controls, IBS
      patients had increased numbers of CD3+, CD4+, and CD8+ T cells and mast cells
      (P<0.001). Compared to male IBS patients, female IBS patients had greater numbers
      of mast cells (P=0.066), but lower numbers of CD3+ and CD8+ T cells (P=0.002 and
      <0.001, respectively). Mucosal mast cell infiltration of IBS patients was
      significantly associated with abdominal bloating frequency (P=0.022) and with
      symptoms of dysmotility-like dyspepsia (P=0.001), but not ulcer-like dyspepsia.
      CONCLUSIONS: A large subset of IBS patients shows gender-dependent mucosal
      infiltration of immunocytes that correlates with abdominal bloating and
      dysmotility-like dyspepsia. These results provide the rationale for considering
      immune mechanisms as a pathophysiological component in a subset of IBS patients.

PMID- 19174798
TI  - Unusual cause of upper gastrointestinal bleed: gastric ulceration and bleed
      secondary to ingested dental bridge.

PMID- 19174799
TI  - Hemorrhagic colitis secondary to acute elemental mercury vapor poisoning.

PMID- 19174800
TI  - Colonoscopy with a transparent hood: simple technique for improved quality of
      colonoscopy.

PMID- 19174801
TI  - Non-variceal upper GI bleeding in patients already hospitalized for another
      condition.
AB  - OBJECTIVES: To compare outpatients (OPs) presenting with non-variceal upper
      gastrointestinal bleeding (NVUGIB) to those who started hemorrhaging while in a
      hospital (inpatients, IPs) in a contemporary setting and to better identify
      predictors of outcome. METHODS: Retrospective data from the Canadian Registry of
      Patients With Upper Gastrointestinal Bleeding Undergoing Endoscopy (RUGBE).
      Descriptive, inferential, and multivariate logistic regression models were
      carried out in 469 IPs (68.5+/-14 years, 36% women) and 1,395 OPs (65.5+/-18
      years, 39% women) in 18 Canadian community and tertiary care centers. RESULTS:
      Main outcomes were rebleeding, mortality, and their predictors. IPs differed from
      OPs in disease acuity (P=0.02) and comorbidities (3.1+/-1.7 vs. 2.3+/-1.5,
      P<0.001), and were admitted longer (7.2+/-7.4 vs. 5+/-5.4 days, P<0.001) and more
      often to intensive care unit (ICU; 40.5% vs. 16%, P<0.001). Ulcers or erosions
      predominated (83% vs. 85%, P=0.28), treated by endotherapy (38% vs. 36%, P=0.46).
      More IPs received proton pump inhibitors (PPIs; 88% vs. 83%, P=0.009). Mortality
      was greater for IPs (11% vs. 3.5%, P<0.001), but rebleeding (15.7% vs. 13.4%,
      P=0.23) and surgery (6.9% vs. 6.4%, P=0.72) were not. Among IPs, comorbidity
      (odds ratio, OR=1.15; 95% confidence interval, CI: 1.01-1.32) and endoscopic high
      risk stigmata increased (OR=3.86, 95% CI:2.05-7.26), whereas PPI decreased
      (OR=0.20, 95% CI:0.10-0.42) rebleeding; high-risk stigmata (OR=3.13, 95% CI:1.23
      7.99) and rebleeding (OR=4.19, 95% CI:2.06-8.55) increased mortality, whereas low
      disease acuity was protective (OR=0.20; 95% CI:0.46-0.90). CONCLUSIONS: IPs are
      sicker than OPs. Endoscopic hemostasis and PPI therapy favorably affect
      rebleeding in IPs, whereas patient characteristics principally determine the
      threefold greater IPs mortality.

PMID- 19174802
TI  - A closer look at mucosal inflammation in irritable bowel syndrome: sex- and
      gender-related disparities--quantity, quality, or both?
AB  - Irritable bowel syndrome remains a bothersome and frustrating disorder that
      imposes a heavy and growing socio-economic toll on its sufferers, two-thirds of
      whom are women, and on health care systems. The biomedical community must take a
      giant step forward into the discipline of women's gastrointestinal health.
      Efforts and accomplishments, such as the one reported in this month's issue by
      Cremon et al., are certainly welcome.

PMID- 19174803
TI  - Radiofrequency thermal ablation vs. percutaneous ethanol injection for small
      hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled
      trials.
AB  - OBJECTIVES: Radiofrequency thermal ablation (RF) and percutaneous ethanol
      injection (PEI) have been employed in the treatment of small hepatocellular
      carcinoma (HCC) as curative treatments. The aim of the study was to review the
      available evidence comparing RF to PEI for small HCC. METHODS:  SEARCH STRATEGY:
      Cochrane, MEDLINE, CANCERLIT, and ENBASE databases were used. SELECTION CRITERIA:
      randomized clinical trials evaluating RF vs. PEI. Data were extracted from each
      randomized controlled trial (RCT). Primary outcomes were overall survival and
      local recurrence. Meta-analysis software was used and risk differences (RDs) and
      their 95% confidence intervals and Q-test for heterogeneity were calculated.
      RESULTS: Five RCTs were identified including 701 patients. The overall survival
      was significantly higher in patients treated with RF than in those treated with
      PEI (RD 0.116, 95% CI 0.173/0.060; heterogeneity not present). Local recurrence
      rate is significantly higher in patients treated with PEI than in those treated
      with RF. In the RF group the 1, 2, and 3 years cancer-free survival rates were
      significantly better than in the PEI-treated patients (respectively: RD 0.098-95%
      CI 0.006/0.189; heterogeneity P=0.57; RD 0.187, 95% CI 0.082/0.293; heterogeneity
      P=0.98; RD 0.210, 95% CI 0.095/0.325; heterogeneity P = 0.78). A small number of
      adverse events were reported in the two treatments. CONCLUSIONS: RF ablation is
      superior to PEI in the treatment of small HCC with respect to overall survival,
      1, 2, and 3 years survival rates, 1, 2, and 3 cancer-free survival rates, and
      tumor response. RF shows a significantly smaller risk of local recurrence.

PMID- 19174804
TI  - Pathology of eosinophilic esophagitis: what the clinician needs to know.
AB  - Eosinophilic esophagitis (EOE) is a clinical pathologic syndrome characterized by
      influx of numerous eosinophils into the esophageal epithelium. It is important
      for clinicians to be aware of the spectrum, as well as the characteristic
      location and distribution, of morphologic changes in EOE to maximize the
      diagnostic yield in mucosal biopsy specimens. The major pathologic features of
      EOE include eosinophilic microabscesses, surface layering of eosinophils often
      associated with surface sloughing of necrotic squamous cells, and peak eosinophil
      counts usually greater than 15 per high power field (hpf) within the squamous
      epithelium. Minor features, which are frequent but less specific, include marked
      basal cell hyperplasia, lengthening of lamina propria papillae, intercellular
      edema, and lamina propria fibrosis with chronic inflammation. The number,
      distribution, and location of intraepithelial eosinophils in EOE vary greatly
      between previously published studies. Thus, utilization of a diagnostic cutoff
      point for intraepithelial eosinophils in EOE, particularly in the absence of
      other major features of EOE, is currently considered unwise. In fact, some
      patients may show combined features of both gastroesophageal reflux disease
      (GERD) and EOE, which complicates the histologic analysis of these patients. In
      contrast to GERD, EOE typically involves longer lengths of the esophagus, affects
      the proximal equally, or even more, than the distal esophagus, and the pathologic
      findings are often patchy in distribution. As a result, it is highly recommended
      that clinicians obtain biopsies from patients suspected of have EOE only after
      treatment with high-dose proton pump inhibitor therapy, and that biopsies be
      obtained from both the proximal and distal esophagus in both normal and abnormal
      appearing areas.

PMID- 19174805
TI  - Re: "The risk of oral contraceptives in the etiology of inflammatory bowel
      disease: a meta-analysis". Response to Cornish et al.

PMID- 19174806
TI  - TNFSF15 polymorphisms are associated with susceptibility to inflammatory bowel
      disease in a new European cohort.
AB  - OBJECTIVES: Inflammatory bowel disease (IBD), e.g., Crohn's disease (CD) and
      ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor
      (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a
      susceptibility gene for CD in Japanese and UK cohorts. This replication study was
      designed in order to confirm and further validate the role of TNFSF15 in IBD.
      METHODS: A total of 666 IBD families (corresponding to 2,982 relatives) with
      European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms,
      which define the main TNFSF15 haplotypes previously associated with CD. An
      association between the main haplotypes and CD, UC and IBD was tested using the
      Genehunter TDT and Unphased statistics. Caspase recruitment domain 15
      (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also
      studied. RESULTS: The previously reported "high-risk" haplotype (A) was
      associated with IBD (P=0.001) (OR=1.25 (1.05-1.50)) and CD (P=0.02) (OR=1.31
      (1.03-1.67)) whereas the "protective" (B) haplotype was significantly less
      transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was
      detected. We also failed to define a clinical subgroup of CD patients
      specifically associated with TNFSF15 haplotype A. CONCLUSIONS: This study
      confirms that TNFSF15 or a closely linked gene is involved in the genetic
      predisposition to CD.

PMID- 19174807
TI  - Management of Crohn's disease in adults.
AB  - Guidelines for clinical practice are intended to suggest preferable approaches to
      particular medical problems as established by interpretation and collation of
      scientifically valid research, derived from extensive review of published
      literature. When data that will withstand objective scrutiny are not available, a
      recommendation may be made based on a consensus of experts. Guidelines are
      intended to apply to the clinical situation for all physicians without regard to
      specialty. Guidelines are intended to be flexible, not necessarily indicating the
      only acceptable approach, and should be distinguished from standards of care that
      are inflexible and rarely violated. Given the wide range of choices in any health
      care problem, the physician should select the course best suited to the
      individual patient and the clinical situation presented. These guidelines are
      developed under the auspices of the American College of Gastroenterology and its
      Practice Parameters Committee. Expert opinion is solicited from the outset for
      the document. The quality of evidence upon which a specific recommendation is
      based is as follows: Grade A: Homogeneous evidence from multiple well-designed
      randomized (therapeutic) or cohort (descriptive) controlled trials, each
      involving a number of participants to be of sufficient statistical power. Grade
      B: Evidence from at least one large well-designed clinical trial with or without
      randomization, from cohort or case-control analytic studies, or well-designed
      meta-analysis. Grade C: Evidence based on clinical experience, descriptive
      studies, or reports of expert committees. The Committee reviews guidelines in
      depth, with participation from experienced clinicians and others in related
      fields. The final recommendations are based on the data available at the time of
      the production of the document and may be updated with pertinent scientific
      developments at a later time.

PMID- 19174808
TI  - Chronic liver disease among Alaska-Native people, 2003-2004.
AB  - OBJECTIVES: A higher proportion of deaths among American-Indian/Alaska-Native
      (AI/AN) people has been attributed to chronic liver disease (CLD) compared with
      other racial/ethnic groups in the United States. The objectives of this study
      were to determine CLD prevalence and to define its etiologies and complications
      among AN and AI people, who received health care from an urban hospital center.
      METHODS: We conducted a retrospective, cross-sectional study of AN and AI people
      > or =18 years old who had at least one patient encounter at the Alaska Native
      Medical Center during January 2003-December 2004. RESULTS: A total of 1,886
      (7.2%) of 26,166 AI/AN people met criteria for having CLD. The most commonly
      identified etiologies were alcohol-related liver disease (42%), nonalcoholic
      fatty liver disease (31%), chronic hepatitis C virus infection (26%), and chronic
      hepatitis B virus infection (8%). Compared with women, men had a higher overall
      prevalence of CLD (81.9 vs. 64.7 per 1,000), but were less likely to die from a
      CLD-related cause (1.5 vs. 2.7 per 1,000). These differences in the CLD deaths
      were mostly attributed to alcohol-related liver disease. CONCLUSIONS: This is the
      first known population-based study to examine the burden and etiology of CLD
      among AN people. Causes of CLD were similar among AI/AN people as those reported
      among other racial/ethnic groups in the United States. Identifying specific
      etiologies of CLD among populations can help target appropriate prevention and
      treatment strategies as they are specific to the causes of CLD.

PMID- 19174809
TI  - Mesalazine and rifaximin in symptomatic uncomplicated diverticular disease.

PMID- 19174810
TI  - A rare cause of upper gastrointestinal bleeding: stromal tumor of duodenum
      masquerading as papilla vateri.

PMID- 19174811
TI  - Helicobacter pylori infection and Barrett's esophagus: a systematic review and
      meta-analysis.
AB  - OBJECTIVES: The majority of distal esophageal adenocarcinomas are believed to
      arise in patients with Barrett's esophagus (BE). Helicobacter pylori (H. pylori)
      infection plays an etiological role in gastric carcinogenesis, but any possible
      role in BE is uncertain. We aimed to explore the possible relationship between H.
      pylori infection and BE by meta-analysis. METHODS: Observational studies
      comparing the prevalence of H. pylori infection in patients with BE and healthy
      controls conducted in adult populations and published in all languages were
      identified through MEDLINE, EMBASE, and Cochrane database searches up to week 5,
      2008. H. pylori infection had to be confirmed by histology and/or serology and/or
      RUT and/or culture. Studies were excluded if no raw data for outcomes of interest
      were available or controls were patients with disease or duplicate publications.
      Summary effect size was calculated as odds ratio (OR) and 95% confidence
      intervals (CIs) by the random-effects model using Review Manager 4.2.8. RESULTS:
      Of 519 citations identified, a total of 12 case-control studies compared the
      prevalence of H. pylori infection in BE (n=550) and controls (9 studies included
      controls with normal endoscopy and 3 studies used healthy blood donors as
      control, n=2,979). There was no significant difference in the overall prevalence
      of H. pylori infection between BE and controls (42.9% vs. 43.9%, OR=0.74, 95% CI
      0.40-1.37, P=0.34), but with significant heterogeneity. Subgroup analysis showed
      that the prevalence of H. pylori infection was significantly lower in BE than in
      endoscopically normal healthy controls (23.1% vs. 42.7%, OR=0.50, 95% CI 0.27
      0.93, P=0.03) with significant heterogeneity observed between studies. The
      heterogeneity was eliminated by excluding a single Asian outlier study. In
      contrast, H. pylori infection was significantly increased in BE patients in the
      three studies using healthy blood donors as "normal controls" (71.2% vs. 48.1%,
      OR=2.21, 95% CI 1.07-4.55). In BE patients, the prevalence of H. pylori infection
      was significantly lower in the esophagus than in the stomach (3.3% vs. 24.7%,
      OR=0.14, 0.03-0.67) in three studies. CONCLUSIONS: H. pylori infection and BE are
      inversely related when compared with endoscopically normal controls but not blood
      donor controls. Limited evidence suggests that there is no clear association
      between H. pylori infection and BE. To determine more accurately the effect size
      of H. pylori infection in BE, high quality prospective case-control studies with
      age-matched, endoscopically normal healthy controls are needed.

PMID- 19174812
TI  - Esophageal adenocarcinoma in Barrett's esophagus after endoscopic ablative
      therapy: a meta-analysis and systematic review.
AB  - OBJECTIVES: The extent of reduction of esophageal adenocarcinoma (EAC) incidence
      in Barrett's esophagus (BE) patients after endoscopic ablation is not known. The
      objective of this study was to determine the cancer incidence in BE patients
      after ablative therapy and compare these rates to cohort studies of BE patients
      not undergoing ablation. METHODS: A MEDLINE search of the literature on the
      natural history and ablative modalities in BE patients was performed. Patients
      with nondysplastic BE (NDBE), low-grade dysplasia (LGD), or high-grade dysplasia
      (HGD) and follow-up of at least 6 months were included. The rate of cancer in
      patients undergoing ablation and from the natural history data was calculated
      using weighted-average incidence rates (WIR). RESULTS: A total of 53 articles met
      the inclusion criteria for the natural history data. Pooled natural history data
      showed cancer incidence of 5.98/1,000 patient-years (95% CI 5.05-6.91) in NDBE;
      16.98/1,000 patient-years (95% CI 13.1-20.85) in LGD; and 65.8/1,000 patient
      years (95% CI 49.7-81.8) in HGD patients. A total of 65 articles met the
      inclusion criteria for BE patients undergoing ablation (1,457 patients, NDBE; 239
      patients, LGD; and 611 patients, HGD). The WIR for cancer was 1.63/1,000 patient
      years (95% CI 0.07-3.34) for NDBE; 1.58/1,000 patient-years (95% CI 0.66-3.84)
      for LGD; and 16.76/1,000 patient-years (95% CI 10.6-22.9) for HGD patients.
      CONCLUSIONS: Compared to historical reports of the natural history of BE,
      ablation may be associated with a reduction in cancer incidence, although such a
      comparison is limited by likely heterogeneity between treatment and natural
      history studies. The greatest benefit of ablation was observed in BE patients
      with HGD.

PMID- 19174814
TI  - Effect of postnatal maturation on the mechanisms of esophageal propulsion in
      preterm human neonates: primary and secondary peristalsis.
AB  - OBJECTIVES: The changes in esophageal propulsive characteristics during
      maturation are not known. Our aim was to define the effects of postnatal
      maturation on esophageal peristaltic characteristics in preterm human neonates.
      We tested the hypotheses that: (i) maturation modifies esophageal bolus
      propulsion characteristics, and (ii) the mechanistic characteristics differ
      between primary and secondary peristalsis. METHODS: Esophageal motility in 10
      premature neonates (mean 27.5 weeks gestational age) was evaluated twice at 33.8
      weeks (time 1, earlier study) and 39.2 weeks (time 2, later study) mean
      postmenstrual age. Esophageal manometry waveform characteristics (amplitude and
      duration, peristaltic velocity, and intrabolus pressure domains) were analyzed
      during spontaneous primary peristalsis and infusion-induced secondary
      peristalsis. Repeated-measures and unstructured variance-covariance or compound
      symmetry matrixes were used for statistical comparison. Values stated as least
      squares means+/-s.e.m. or percent. RESULTS: A total of 200 primary peristalsis
      and 227 secondary peristalsis events were evaluated. Between time 1 and time 2:
      (i) proximal esophageal waveform amplitude increased (P<0.02), with primary
      peristalsis (38+/-6 vs. 48+/-7 mm Hg) and with secondary peristalsis (34+/-6 vs.
      46+/-5 mm Hg); (ii) distal esophageal waveform amplitude was similar (P=NS), with
      primary peristalsis (42+/-4 vs. 43+/-4 mm Hg) and secondary peristalsis (29+/-3
      vs. 32+/-4 mm Hg); (iii) proximal esophageal waveform onset to peak duration
      decreased (P=0.02) with primary (2.6+/-0.3 vs. 1.9+/-0.1 s, P<0.003) and with
      secondary peristalsis (2.2+/-0.2 vs. 1.8+/-0.1 s); (iv) distal esophageal
      waveform onset to peak duration decreased (P=0.01) with primary (2.4+/-0.3 vs.
      1.8+/-0.1 s) and with secondary peristalsis (1.9+/-0.2 vs. 1.5+/-0.1 s); (v)
      effects of identical stimulus volume on intrabolus pressure were similar (P=NS);
      however, greater infusion volumes (2 vs. 1 ml) generated higher intrabolus
      pressure at both time 1 and time 2 (both Ps<0.05). Between primary and secondary
      peristalsis (mechanistic variable): (i) no differences were noted at either
      period, with proximal esophageal waveform amplitudes (P=NS); (ii) differences
      were noted with distal esophageal waveform amplitudes at each time period
      (P=0.0002); (iii) no differences were noted with both esophageal waveforms
      duration at either period (P=NS); (iv) peristaltic velocity was faster with
      secondary peristalsis than with primary peristalsis at either period (at earlier
      study, 7.9+/-1.4 vs. 2.5+/-1.4 cm/s and at later study 6.2+/-1.6 vs. 1.2+/-1.5
      cm/s, both Ps<0.01). CONCLUSIONS: In preterm neonates, longitudinal maturation
      modulates the characteristics of primary and secondary peristalsis. Differences
      in proximal striated muscle and distal smooth muscle activity during peristalsis
      are evident. Peristaltic velocity is faster with secondary peristalsis. These
      findings may represent maturation of central and peripheral neuromotor properties
      of esophageal bolus propulsion in healthy preterm human neonates.

PMID- 19174815
TI  - Dietary antigens in Crohn's disease.

PMID- 19174816
TI  - Central vs. bilateral endoscopic ultrasound-guided celiac plexus block or
      neurolysis: a comparative study of short-term effectiveness.
AB  - OBJECTIVES: Endoscopic ultrasound (EUS)-guided celiac plexus block/neurolysis
      (CPB/N) can be performed by injecting at the base (central) or on either side
      (bilateral) of the celiac axis. Central CPB/N is easier and possibly safer.
      Bilateral CPB/N is more difficult but may be more effective as it reaches more
      ganglia. The aim of this study was to compare the short-term safety and efficacy
      of central and bilateral CPB/N. METHODS: Consecutive patients referred for CPB/N
      to a quaternary EUS center were eligible for this study. Central CPB/N was used
      in the first half of the study period and bilateral CPB/N in the last half. The
      primary outcome was the percent reduction in visual analog pain scores at day 7.
      RESULTS: A total of 184 patients were eligible. Out of them, 24 (13%) were
      excluded for incomplete data. A total of 160 were left (71 central, 89
      bilateral). The groups were similar for all cogent variables. Bilateral CPB/N was
      more effective than central CPB/N (mean percent pain reduction 70.4% (61.0-80.0)
      vs. 45.9% (32.7-57.4); P=0.0016). The only predictor of a >50% pain reduction was
      bilateral CPB/N (odds ratio 3.55, 1.72-7.34). Only one complication was noted:
      self-limited bleeding because of laceration of the adrenal artery following
      bilateral celiac plexus (CP) block in an anticoagulated patient. CONCLUSIONS: (i)
      Bilateral CPB/N is more effective than central CPB/N; (ii) bilateral CPB/N is
      safe, but on rare occasions can cause trauma to the left adrenal artery; it
      should therefore be avoided in patients with a bleeding diathesis.

PMID- 19174817
TI  - Eosinophilic esophagitis with severe GERD.

PMID- 19174818
TI  - Statins and pancreatic cancer: are all statins the same?

PMID- 19174819
TI  - Epidermal growth factor receptor kinase domain mutations are rare in salivary
      gland carcinomas.
AB  - Activating mutations within the epidermal growth factor (EGFR) tyrosine kinase
      domain identify non-small cell lung cancer patients with improved clinical
      response to tyrosine kinase inhibitor therapy. Recently, we identified two EGFR
      mutations in a cohort of 25 salivary gland carcinomas (SGCs) by screening the
      tumour samples for the both most common hotspot mutations in exons 19 and 21 by
      allele-specific PCR. Here, we present a comprehensive sequencing analysis of the
      entire critical EGFR tyrosine kinase domain in 65 SGC of the main
      histopathological types. We found EGFR mutations in the tyrosine kinase domain to
      be a rare event in SGCs. No additional mutations other than the two known exon 19
      deletions (c.2235_2249del15) in a mucoepidermoid carcinoma and an adenoid cystic
      carcinoma have been detected. Other putative predictive markers for EGFR-targeted
      therapy in SGCs might be relevant and should be investigated.

PMID- 19174820
TI  - Trends in the incidence of primary liver cancer in Central Uganda, 1960-1980 and
      1991-2005.
AB  - Primary liver cancer (PLC) incidence trends from Africa are unknown. Using
      Kampala Cancer Registry data from 1960 to 1980 and 1991 to 2005, we identified
      771 PLCs. Although rates were stable among men, PLC incidence among women
      increased >50%. Investigations of viral hepatitis, aflatoxin, obesity, and human
      immunodeficiency virus (HIV) may help to explain the increasing incidence of
      hepatocellular carcinomas (HCCs).

PMID- 19174821
TI  - Urinary tract infections and reduced risk of bladder cancer in Los Angeles.
AB  - We investigated the association between urinary tract infections (UTIs) and
      transitional cell carcinoma of the bladder in a population-based case-control
      study in Los Angeles covering 1586 cases and age-, gender-, and race-matched
      neighbourhood controls. A history of bladder infection was associated with a
      reduced risk of bladder cancer among women (odds ratio (OR), 0.66; 95% confidence
      interval (CI), 0.46-0.96). No effect was found in men, perhaps due to power
      limitations. A greater reduction in bladder cancer risk was observed among women
      with multiple infections (OR, 0.37; 95% CI, 0.18-0.78). Exclusion of subjects
      with a history of diabetes, kidney or bladder stones did not change the inverse
      association. A history of kidney infections was not associated with bladder
      cancer risk, but there was a weak association between a history of other UTIs and
      slightly increased risk among men. Our results suggest that a history of bladder
      infection is associated with a reduced risk of bladder cancer among women.
      Cytotoxicity from antibiotics commonly used to treat bladder infections is
      proposed as one possible explanation.

PMID- 19174822
TI  - Cancer risk in hospitalised asthma patients.
AB  - Asthma is an increasingly common disorder, affecting 5-10% of the population. It
      involves a dysregulated immune function, which may predispose to subsequent
      cancer. We examined cancer risk among Swedish subjects who had hospital admission
      once or multiple times for asthma. An asthma research database was created by
      identifying asthma patients from the Swedish Hospital Discharge Register and by
      linking them with the Cancer Registry. A total of 140 425 patients were
      hospitalised for asthma during 1965-2004, of whom 7421 patients developed cancer,
      giving an overall standardised incidence ratio (SIR) of 1.36. A significant
      increase was noted for most sites, with the exception of breast and ovarian
      cancers and non-Hodgkin's lymphoma and myeloma. Patients with multiple hospital
      admissions showed a high risk, particularly for stomach (SIR 1.70) and colon (SIR
      1.99) cancers. A significant decrease was noted for endometrial cancer and skin
      melanoma. Oesophageal and lung cancers showed high risks throughout the study
      period, whereas stomach cancer increased towards the end of the period. The
      relatively stable temporal trends suggest that the asthmatic condition rather
      than its medication is responsible for the observed associations.

PMID- 19174823
TI  - Prime time for a polypill after myocardial infarction?

PMID- 19174824
TI  - Prospective, observational study of antiplatelet and coagulation biomarkers as
      predictors of thromboembolic events after implantation of ventricular assist
      devices.
AB  - BACKGROUND: Long-term success in ventricular assist device (VAD) recipients is
      limited by thromboembolic events, the prediction of which remains elusive. We
      evaluated the predictive value of aspirin hyporesponsiveness and markers of
      coagulation and fibrinolysis. METHODS: We prospectively enrolled patients
      scheduled to undergo VAD implantation between June 2004 and March 2006. Once
      before surgery, daily during hospitalization, and weekly after discharge we
      assessed platelet function, measured prothrombin activation fragment 1.2 (F1.2)
      and plasminogen activator inhibitor-1 (PAI-1) concentrations, and evaluated
      aspirin hyporesponsiveness by whole-blood aggregometry and thromboelastography.
      All patients received 325 mg oral aspirin daily from at least 7 days before VAD
      implantation. Follow-up continued until heart transplantation, death or closure
      of the database. RESULTS: We included 26 patients (median follow-up 315 days,
      range 9-833 days). In eight (31%) patients, 14 thromboembolic events occurred at
      a median of 42 (interquartile range 26-131) days. Only six (43%) events based on
      whole-blood aggregometry and one (7%) based on thromboelastography coincided with
      aspirin hyporesponsiveness. Within-patient variability was high for both tests
      (59% and 567%, respectively). Compared with levels before surgery, PAI-1
      concentrations were raised for up to 45 days (P <0.0001) and those of F1.2 for up
      to 3 days (P = 0.0001) after VAD implantation. PAI-1 and F1.2 levels did not rise
      significantly further before thromboembolic events. CONCLUSIONS: Aspirin
      hyporesponsiveness was not associated with raised risk of future clinical
      thromboembolic events after VAD implantation. Impaired fibrinolysis, demonstrated
      by raised PAI-1 concentrations, might, however, indicate a predisposition to such
      events early after surgery.

PMID- 19174826
TI  - Active dilation of penetrating arterioles restores red blood cell flux to
      penumbral neocortex after focal stroke.
AB  - Pial arterioles actively change diameter to regulate blood flow to the cortex.
      However, it is unclear whether arteriole reactivity and its homeostatic role of
      conserving red blood cell (RBC) flux remains intact after a transient period of
      ischemia. To examine this issue, we measured vasodynamics in pial arteriole
      networks that overlie the stroke penumbra during transient middle cerebral artery
      occlusion in rat. In vivo two-photon laser-scanning microscopy was used to obtain
      direct and repeated measurements of RBC velocity and lumen diameter of individual
      arterioles, from which the flux of RBCs was calculated. We observed that
      occlusion altered surface arteriole flow patterns in a manner that ensured
      undisrupted flow to penetrating arterioles throughout the imaging field. Small
      diameter arterioles (<23 microm), which included 88% of all penetrating
      arterioles, exhibited robust vasodilation over a 90-min occlusion period.
      Critically, persistent vasodilation compensated for an incomplete recovery of RBC
      velocity during reperfusion to enable a complete restoration of postischemic RBC
      flux. Further, histologic examination of tissue hypoxia suggested re-oxygenation
      through all cortical layers of the penumbra. These findings indicate that
      selective reactivity of small pial arterioles is preserved in the stroke penumbra
      and acts to conserve RBC flux during reperfusion.

PMID- 19174828
TI  - Utilizing predictive resident-focused problems to improve nutritional outcomes in
      nursing homes.
AB  - The purpose of this article is to describe nutritional problems that may be
      predictive of poor resident outcomes in nursing homes. In a recent study, seven
      resident-focused problems or categories that may affect malnutrition and/or food
      intake were identified (Crogan and Alvine, 2006; Crogan et al., 2007). Regression
      analysis found that three of seven resident-focused problems were predictive of
      low serum prealbumin levels, impaired functional status and improved quality of
      life.

PMID- 19174829
TI  - The effects of whole milk and infant formula on growth and IGF-I in late infancy.
AB  - BACKGROUND/OBJECTIVES: High protein intake has been associated with increased
      growth. This may be linked to increased concentrations of insulin-like growth
      factor I (IGF-I), which seems to be influenced by the diet, especially its
      protein component. The short-term effects of high protein intake in late infancy
      are not known. The objective was to investigate the effects of high protein
      intake in the form of whole milk (WM) on growth and IGF-I from 9 to 12 months of
      age. SUBJECTS/METHODS: Healthy infants (n=83) were randomized to receive either
      WM or infant formula and fish oil or no fish oil (2 x 2 design). Anthropometric
      variables, IGF-I concentrations, serum urea nitrogen (SUN) and diet were recorded
      before and after the intervention. RESULTS: Intake of WM significantly increased
      the protein energy percentage (PE%; P< or =0.001) and SUN (P=0.01), whereas there
      was no effect on size. The milk intervention increased IGF-I in boys (P=0.034)
      but not in girls. Intake of fish oil had no effect on the outcomes. Including all
      infants in the analysis there was a significant correlation between weight and
      IGF-I at 12 months (r=0.316, P=0.017), and PE% was positively associated with IGF
      I after adjusting for sex and breastfeeding at both 9 (r=0.329, P=0.015) and 12
      months (r=0.272, P=0.044). CONCLUSIONS: Randomization to WM had no overall effect
      on growth. However, the positive effect of WM on IGF-I in boys and the positive
      association between PE% intake and IGF-I at 9 and 12 months is consistent with
      the hypothesis that a high milk intake stimulates growth.

PMID- 19174831
TI  - Mostly, your results matter to others.
AB  - High-throughput datasets and analysis protocols are intrinsically difficult to
      referee. Community standards enforced by journals may be less effective than is
      widely appreciated. Greater awareness of the needs and value of secondary data
      users can result in higher-impact papers.

PMID- 19174830
TI  - Effect of micronutrient supplementation on diarrhoeal disease among stunted
      children in rural South Africa.
AB  - BACKGROUND/OBJECTIVE: The efficacy of zinc combined with vitamin A or multiple
      micronutrients in preventing diarrhoea is unclear in African countries with high
      prevalence of human immunodeficiency virus (HIV)-exposed children. Potential
      modifying factors, such as stunting, need to be addressed. The objective of this
      study was to determine whether adding zinc or zinc plus multiple micronutrients
      to vitamin A reduces diarrhoea incidence, and whether this differs between the
      strata of stunted or HIV-infected children. METHODS: We analyzed data from a
      randomized, controlled, double-blinded trial (ClinicalTrials.gov NCT00156832) of
      prophylactic micronutrient supplementation to children aged 6-24 months. Three
      cohorts of children: 32 HIV-infected children, 154 HIV-uninfected children born
      to HIV-infected mothers and 187 uninfected children born to HIV-uninfected
      mothers, received vitamin A, vitamin A plus zinc or multiple micronutrients,
      which included vitamin A and zinc. The main outcome was incidence of diarrhoea.
      Poisson regression was used in intent-to-treat analyses. Stratified analyses
      followed testing for statistical interaction between intervention and stunting.
      RESULTS: We observed no significant differences in overall diarrhoea incidence
      among treatment arms. Stunting modified this effect with stunted HIV-uninfected
      children having significantly lower diarrhoea incidence when supplemented with
      zinc or multiple micronutrients compared with vitamin A alone (2.04 and 2.23 vs
      3.92 episodes/year, respectively, P=0.024). No meaningful subgroup analyses could
      be done in the cohort of HIV-infected children. CONCLUSIONS: Compared with
      vitamin A alone, supplementation with zinc and with zinc and multiple
      micronutrients, reduced diarrhoea morbidity in stunted rural South African
      children. Efficacy of zinc supplementation in HIV-infected children needs
      confirmation in studies that represent the spectrum of disease severity and age
      groups.

PMID- 19174833
TI  - A supersized list of obesity genes.

PMID- 19174834
TI  - Hair lost in translation.

PMID- 19174835
TI  - Reverse evolution and evolutionary memory.

PMID- 19174836
TI  - Integrative genetical genomics in Arabidopsis.

PMID- 19174839
TI  - How well do evolutionary trees describe genetic relationships among populations?
AB  - Bifurcating evolutionary trees are commonly used to describe genetic
      relationships between populations, but may not be appropriate for populations
      that did not evolve in a hierarchical manner. The degree to which bifurcating
      trees distort genetic relationships between populations can be quantified with
      R(2), the proportion the variation in a matrix of genetic distances between
      populations that is explained by a tree. Computer simulations were used to
      measure how well the unweighted pair group method with arithmetic mean (UPGMA)
      and neighbor-joining (NJ) trees depicted population structure for three
      evolutionary models: a hierarchical model of population fragmentation, a linear
      stepping-stone model of gene flow and a two-dimensional stepping-stone model of
      gene flow. These simulations showed that the UPGMA did an excellent job of
      describing population structure when populations had a bifurcating history of
      fragmentation, but severely distorted genetic relationships for the linear and
      two-dimensional stepping-stone models. The NJ algorithm worked well in a broader
      range of evolutionary histories, including the linear stepping-stone model. A
      computer program for performing the calculations described in this study is
      available for download at www.montana.edu/kalinowski.

PMID- 19174838
TI  - Repeatability of published microarray gene expression analyses.
AB  - Given the complexity of microarray-based gene expression studies, guidelines
      encourage transparent design and public data availability. Several journals
      require public data deposition and several public databases exist. However, not
      all data are publicly available, and even when available, it is unknown whether
      the published results are reproducible by independent scientists. Here we
      evaluated the replication of data analyses in 18 articles on microarray-based
      gene expression profiling published in Nature Genetics in 2005-2006. One table or
      figure from each article was independently evaluated by two teams of analysts. We
      reproduced two analyses in principle and six partially or with some
      discrepancies; ten could not be reproduced. The main reason for failure to
      reproduce was data unavailability, and discrepancies were mostly due to
      incomplete data annotation or specification of data processing and analysis.
      Repeatability of published microarray studies is apparently limited. More strict
      publication rules enforcing public data availability and explicit description of
      data processing and analysis should be considered.

PMID- 19174840
TI  - Properties of re-arranged P elements in Drosophila melanogaster.
AB  - P elements, both complete and incomplete, contain a left and right end, normally
      depicted as pointing away from each other. Here, we examine the properties of P
      elements that may be described as 're-arranged elements' or 'inside-out
      elements', containing inverted ends. Two such structures exist, having either
      ends pointing towards each other, 'head-to-head or H-H', or ends pointing in the
      same direction 'head-to-tail or H-T'. We show that both structures are unstable
      in the presence of P element transposase. For the H-H element there is a high
      frequency of deletion of the intervening material and almost exact rejoining of
      element ends with the 4 bp CATG palindromic end sequence shared by the two
      element ends. This result is predicted by the Beall and Rio model of P element
      excision. For the H-T element there is a high frequency of exact excision of the
      entire inverted right-end, a result again predicted by the Beall and Rio model.
      Both structures lead to recombination in the way expected from a normal element.
      The rates of recombination are, however, much lower than might be expected from
      the organization of ends, a result that can be explained in terms of the low
      likelihood of insertion into a chromosomal region lacking another P element end.
      We also investigate the properties of combinations of re-arranged and normal
      elements, and show that there is a directionality property when left and right
      ends are combined in trans that can be explained in terms of strand repair.

PMID- 19174841
TI  - Trends in causes of death among older persons in the United States.

PMID- 19174843
TI  - Health tips.  Lighting for low vision.

PMID- 19174842
TI  - Trends in prescribed medicine use and spending by older Americans, 1992-2001.

PMID- 19174844
TI  - Taking the stairs: even small habit changes improve health.

PMID- 19174845
TI  - Traveler's diarrhea.  Preventing a vacation wrecker.

PMID- 19174846
TI  - Cutting drug costs.  Brand names go generic.

PMID- 19174847
TI  - I take calcium supplements for my bones.  Should I take magnesium supplements to
      help my bones absorb the calcium?  I've heard the two work better together.

PMID- 19174848
TI  - Z-DNA crystallography .
AB  - We review the effect of sequence on the structure of left-handed Z-DNA in single
      crystals. The various substituent groups that define a nucleotide base as
      guanine, cytosine,thymine, or adenine affect both the DNA conformation and the
      organization of solvent around the duplex. These are discussed in terms of their
      effect on the ability of sequences to adopt the unusual Z-DNA structure. In
      addition, the experimental and theoretical methods used to treat DNA hydration
      are discussed as they relate to the stability of Z-DNA . Finally, we argue that Z
      DNA , as defined by the crystal conformation, is sufficient in itself to account
      for the physical properties of left-handed conformations observed in polymers and
      in genomic sequences

PMID- 19174849
TI  - Effects of laser radiation on Rhus vernicifera laccase, Type 2 Cu-depleted
      laccase, and stellacyanin.
AB  - Laser irradiation in the 450 nm region brings about irreversible changes in the
      copper sites of Rhus vernicifera lactase and its type 2 Cu-depleted derivative.
      The absorption band at 614 nm disappears after _ 2 hr of irradiation with a 200
      mW laser beam; the amount of the paramagnetic detectable copper does not
      decrease, indicating no reduction of these types of copper. No apparent
      rearrangement of the protein backbone occurs, as ultaviolet dichroic spectra of
      the enzyme before and after the irradiation do not show appreciable differences.
      Stellacyanin is insensitive to laser radiation at any wavelength.

PMID- 19174850
TI  - A resonance Raman study of native stellacyanin and its Ni(II) derivative. On the
      origin of the 450-nm electronic absorption.
AB  - The resonance Raman spectra of native stellacyanin and its Ni(II) derivative has
      been investigated. Raman intensity as a function of the exciting frequency shows
      minima at about 440--460 nm. Moreover, the resonance Raman spectra of the Ni(II)
      derivative indicate similar symmetry and nature of ligands, namely, one cysteine
      and at least one histidine.Optical electronegativity of the ligand involved in
      the intense visible absorption band of native stellacyanin and the corresponding
      transition of the Ni(lI) derivative confirm this assumption. The origin of the
      450 nm band is also discussed.

PMID- 19174851
TI  - [A young woman with adverse effects of neuroleptics].

PMID- 19174852
TI  - [Neuropsychiatric disease with hematological findings].

PMID- 19174853
TI  - Quantification and characterisation of suspended particulate matter in indoor
      air.
AB  - Quantification and characterisation of suspended particulate matter (SPM) from
      homes in the city of Oslo was carried out. In 29 households the dust
      concentrations were found to vary between 9 and 56 mug/m(3) (median value 26
      mug/m (3)). In 12 of the 29 households, a thorough analysis was carried out to
      determine the size and element distribution of the particles using transmission
      electron microscopy (TEM) and X-ray microanalysis (XRMA). The vast majority of
      the collected particles were less than 2.5 mum in diameter, i.e. they belonged to
      the fine fraction. In this fraction a considerable amount of soot and sulphur
      particles were found, usually less than 1 mum in diameter. The coarse fraction
      (particles > 2.5 mum in diameter) was found to consist mainly of organic
      material, silicates and larger soot aggregates. Both a thorough analysis of
      individual particles and a "bulk analysis" (i.e. recording XRMA spectra from
      whole grid masks) were performed, and the two methods were found to show good
      agreement.

PMID- 19174854
TI  - Trends in health status and health care use among older women.

PMID- 19174855
TI  - Trends in influenza and pneumonia among older persons in the United States.

PMID- 19174856
TI  - Multiple causes of death in old age.

PMID- 19174857
TI  - Methods in molecular biology. Introduction.

PMID- 19174858
TI  - [Pavel Vasil'evich Dunaev (on his 80-th birthday)].

PMID- 19174859
TI  - Humoral immunity in kidney transplantation: what clinicians need to know.
      Preface.

PMID- 19174860
TI  - Pesticide triggers a food chain cascade.

PMID- 19174861
TI  - Can wetland restoration cool the planet?

PMID- 19174862
TI  - Why small plastic particles may pose a big problem in the oceans.

PMID- 19174863
TI  - Toward cleaner oceans.

PMID- 19174864
TI  - Ecological risk assessment: from book-keeping to chemical stress ecology.

PMID- 19174865
TI  - Adsorption mechanisms of organic chemicals on carbon nanotubes.
AB  - Carbon nanotubes (CNTs) have drawn special research attention because of their
      unique properties and potential applications. This review summarizes the research
      progress of organic chemical adsorption on CNTs, and will provide useful
      information for CNT application and risk assessment. Adsorption heterogeneity and
      hysteresis are two widely recognized features of organic chemical-CNT
      interactions. However, because different mechanisms may act simultaneously,
      mainly hydrophobic interactions, pi-pi bonds, electrostatic interactions, and
      hydrogen bonds, the prediction of organic chemical adsorption on CNTs is not
      straightforward. The dominant adsorption mechanism is different for different
      types of organic chemicals (such as polar and nonpolar), thus different models
      may be needed to predict organic chemical-CNT interaction. Adsorption mechanisms
      will be better understood by investigating the effects of properties of both CNTs
      and organic chemicals along with environmental conditions. Another majorfactor
      affecting adsorption by CNTs is their suspendability, which also strongly affects
      their mobility, exposure, and risk in the environment. Therefore, organic
      chemical-CNT interactions as affected by CNT dispersion and suspending merit
      further experimental research. In addition, CNTs have potential applications in
      water treatment due to their adsorption characteristics. Thus column and pilot
      studies are needed to evaluate their performance and operational cost.

PMID- 19174866
TI  - Fuel-mercury combustion emissions: an important heterogeneous mechanism and an
      overall review of its implications.
AB  - An extensive examination of combustion gases containing trace amounts of mercury
      shows unambiguously mercury's propensity for heterogeneous chemistry. Although
      additional mechanisms for the oxidation chemistry of mercury have been implied by
      the continuing inadequacy of modeling attempts, details of the specific chemistry
      have remained unknown. Now it is shown that mercury can efficiently chemi-deposit
      onto surfaces encountered in practical combustors. If sulfur is present,
      condensed mercuric sulfate forms momentarily. This is then converted by gaseous
      HCl to HgCl2 that may sublime into the flow or be retained. This elusive and
      efficient noncatalytic mechanism most likely explains the observed fractional
      conversions to the dichloride observed in coal combustors. A receptive surface
      acts solely as an intermediary, facilitating the conversion while disguising its
      role. Without sulfur, a corresponding mechanism occurs but via HgO that is
      similarly converted to the dihalide. Such heterogeneous dynamics have significant
      repercussions for both full-scale combustors and bench-type experiments, which
      data have been reassessed and reviewed. Conclusions imply that observations
      concerning mercury will be system dependent and no two combustors can be exactly
      alike. The re-examination of prior work provides significant support for these
      conclusions. This fundamental understanding now lays a foundation for meaningful
      interpretations and program planning. It has indicated also the extreme care
      needed in sampling and monitoring the speciation of mercury in such combustion
      flows for reliable results. It now points to a simple low-cost surface-induced
      mitigation method for effectively converting the mercury in flue gases to the
      water-soluble dichloride. It is in essence no more than an optimization of the
      natural process that is currently occurring in combustors but to only limited
      degrees.

PMID- 19174867
TI  - Expert assessments of future photovoltaic technologies.
AB  - Subjective probabilistic judgments about future module prices of 26 current and
      emerging photovoltaic (PV) technologies were obtained from 18 PV technology
      experts. Fourteen experts provided detailed assessments, including likely future
      efficiencies and prices under four policy scenarios. While there is considerable
      dispersion among the judgments, the results suggest a high likelihood that some
      PV technology will achieve a price of $1.20/Wp by 2030. Only 7 of 18 experts
      assess a better-than-even chance that any PV technology will achieve $0.30/Wp by
      2030; 10 of 18 experts give this assessment by 2050. Given these odds, and the
      wide dispersion in results, we conclude that PV may have difficulty becoming
      economically competitive with other options for large-scale, low-carbon bulk
      electricity in the next 40 years. If $0.30/Wp is not reached, then PV will likely
      continue to expand in markets other than bulk power. In assessing different
      policy mechanisms, a majority of experts judged that R&D would most increase
      efficiency, while deployment incentives would most decrease price. This implies a
      possible disconnect between research and policy goals. Governments should be
      cautious about large subsidies for deployment of present PV technology while
      continuing to invest in R&D to lower cost and reduce uncertainty.

PMID- 19174868
TI  - Polymeric brominated flame retardants: are they a relevant source of emerging
      brominated aromatic compounds in the environment?
AB  - A purge and trap method was used to study the release of brominated organic
      compounds from polymeric brominated flame retardants (BFRs), a relatively unknown
      class of flame retardant materials. Among the volatile brominated organics
      released, pentabromotoluene (PBTo), pentabromoethylbenzene (PBEB), and
      hexabromobenzene (HBB) were of particular interest because of their high
      potential to persist in the environment The impact of a thermal stress on the
      release of these compounds was assessed by applying different constant
      temperatures for one hour to a polymeric BFR sample. Release rates ranged between
      22 +/- 2.1 ng g(-1) h(-1) for PBEB to 2480 +/- 500 ng g(-1) h(-1) for PBTo at
      room temperature. These rates of release reached 65 +/- 11 ng g(-1) h(-1) for
      PBEB and 42400 +/- 4700 ng g(-1) h(-1) for PBTo at 100 degrees C. This suggests
      that the compounding of thermoplastic polyesters done at high temperatures, up to
      290 degrees C, could lead to the release of significant amounts of volatile
      brominated compounds in the environment when crude polymeric BFRs are used as
      flame retardants. To assess if this unsuspected source of volatile brominated
      compounds to the environment was relevant to support air concentrations in the
      Great Lakes area, air samples collected at Egbert (ON, Canada) were analyzed and
      PBTo, PBEB, and HBB were detected at low levels in some air samples (<0.01 to
      0.09 pg/m3). As a second step, a Level III fugacity model was run using release
      rates of PBTo, PBEB, and HBB determined in this study. Results of the model
      indicated that prevailing PBEB and HBB air concentrations were not supported by
      their release from polymeric BFRs but by the use of these compounds as additive
      BFRs. However, these model predictions suffered from a lack of information on the
      actual use of polymeric BFRs. Hence, further work is needed to assess the release
      of potentially persistent brominated aromatic compounds from polymeric BFRs.

PMID- 19174869
TI  - Speciation of antimony in PET bottles produced in Japan and China by X-ray
      absorption fine structure spectroscopy.
AB  - The oxidation state and coordination environment of antimony (Sb) incorporated
      into polyethylene terephthalate (PET) bottles were estimated based on X-ray
      absorption fine structure (XAFS) at Sb K-edge. Prior to XAFS analyses, Sb
      concentrations in 177 PET bottles collected in Japan and China were determined,
      showing that 30.5% and 100% of Japanese and Chinese PET bottles, respectively,
      contained more than 10 mg/kg of Sb. Most of the bottles used for aseptic cold
      filling and carbonated drinks contained a larger amount of Sb. Extended X-ray
      absorption fine structure (EXAFS) showed that the first neighboring atom of Sb in
      PET was estimated to be oxygen with a coordination number of about three. In
      addition, the contribution of Sb to Sb shell was discounted in the EXAFS, showing
      that Sb was not present as Sb2O3 in PET, although Sb was initially added as Sb2O3
      in the production of PET. This information is consistent with the coordination
      environment estimated from the polycondensation reaction catalyzed by Sb, where
      Sb can be present as either Sb glycolate or Sb glycolate binding to the end group
      of the PET polymer. X-ray absorption near-edge structure (XANES) showed that
      Sb(III) initially added as Sb2O3 into PET was partially oxidized and the Sb(V)
      fractions reached approximately 50% in some samples. However, the oxidation state
      and coordination environment of Sb in PET had no relationship with the
      concentrations of Sb that leached into water from PET. Based on the present XAFS
      results and previous studies on the effects of temperature and others, it was
      concluded that the leaching behavior of Sb into water is primarily due to the
      degradation of PET itself, but is not related to the Sb species in the PET
      bottles.

PMID- 19174870
TI  - Chemical compositions of subway particles in Seoul, Korea determined by a
      quantitative single particle analysis.
AB  - A novel single particle analytical technique, low-Z particle electron probe X-ray
      microanalysis, was applied to characterize seasonal subway samples collected at a
      subway station in Seoul, Korea. For all 8 samples collected twice in each season,
      4 major types of subway particles, based on their chemical compositions, are
      significantly encountered: Fe-containing; soil-derived; carbonaceous; and
      secondary nitrate and/or sulfate particles. Fe-containing particles are generated
      indoors from wear processes at rail-wheel-brake interfaces while the others may
      be introduced mostly from the outdoor urban atmosphere. Fe-containing particles
      are the most frequently encountered with relative abundances in the range of 61
      79%. In this study, it is shown that Fe-containing subway particles almost always
      exist either as partially or fully oxidized forms in underground subway
      microenvironments. Their relative abundances of Fe-containing particles increase
      as particle sizes decrease. Relative abundances of Fe-containing particles are
      higher in morning samples than in afternoon samples because of heavier train
      traffic in the morning. In the summertime samples, Fe-containing particles are
      the most abundantly encountered, whereas soil-derived and nitrate/sulfate
      particles are the least encountered, indicating the air-exchange between indoor
      and outdoor environments is limited in the summer, owing to the air-conditioning
      in the subway system. In our work, it was observed that the relative abundances
      of the particles of outdoor origin vary somewhat among seasonal samples to a
      lesser degree, reflecting that indoor emission sources predominate.

PMID- 19174871
TI  - Atmospheric deposition of PBDEs to the Great Lakes featuring a Monte Carlo
      analysis of errors.
AB  - The first estimates of atmospheric deposition of polychlorinated diphenyl ethers
      (PBDEs) into the Great Lakes are presented. Precipitation samples were collected
      monthly from 2005 to 2006 at five sites located in the Great Lakes region. Volume
      weighted mean concentrations of total PBDEs in precipitation ranged from 94 +/-
      19 ng L(-1) at the urban site of Chicago to 0.65 +/- 0.14 ng L(-1) for the rural
      site of Sturgeon Point Using gas and particle phase concentrations previously
      obtained in our laboratory and concentrations in precipitation measured in this
      study, the total annual net mass transfer rates to each lake and their relative
      errors were calculated using Monte Carlo analysis. The highest net mass transfer
      rates for BDE-47, and total PBDEs were measured for Lake Michigan (150 +/- 40 and
      310 +/- 79 kg y(-1), respectively) while the highest net mass transfer rate for
      BDE-209 was measured for Lake Erie (79 +/- 56 kg y(-1)). We found good agreement
      between atmospheric and sediment net mass transfer rates for Lake Superior, but
      we found a significant imbalance of BDE-209 for the other two lakes and of BDE-47
      for Lake Michigan. These findings suggest that Chicago might be a preferential
      source of BDE-47 to Lake Michigan and that Cleveland might be a preferential
      source of BDE-209 to Lake Erie.

PMID- 19174872
TI  - Spatial and temporal variation of freely dissolved polycyclic aromatic
      hydrocarbons in an urban river undergoing Superfund remediation.
AB  - Urban rivers with a history of industrial use can exhibit spatial and temporal
      variations in contaminant concentrations that may significantly affect risk
      evaluations and even the assessment of remediation efforts. Concentrations of 15
      biologically available priority pollutant polycyclic aromatic hydrocarbons (PAHs)
      were measured over five years along 18.5 miles of the lower Willamette River
      using passive sampling devices and HPLC. The study area includes the Portland
      Harbor Superfund megasite with several PAH sources including remediation
      operations for coal tar at RM 6.3 west and an additional Superfund site,
      McCormick and Baxter, at RM 7 east consisting largely of creosote contamination.
      Study results show that organoclay capping at the McCormick and Baxter Superfund
      Site reduced PAHs from a precap average of 440 +/- 422 ng/L to 8 +/- 3 ng/L
      postcapping. Results also reveal that dredging of submerged coal tar nearly
      tripled nearby freely dissolved PAH concentrations. For apportioning sources,
      fluoranthene/pyrene and phenanthrene/anthracene diagnostic ratios from passive
      sampling devices were established for creosote and coal tar contamination and
      compared to published sediment values.

PMID- 19174874
TI  - Correlations between water-soluble organic aerosol and water vapor: a synergistic
      effect from biogenic emissions?
AB  - Ground-based measurements of meteorological parameters and water-soluble organic
      carbon in the gas(WSOCg) and particle (WSOCp) phases were carried out in Atlanta,
      Georgia, from May to September 2007. Fourteen separate events were observed
      throughout the summer in which WSOCp and water vapor concentrations were highly
      correlated (average WSOCp-water vapor r = 0.92); however, for the entire summer,
      no well-defined relationship existed between the two. The correlation events,
      which lasted on average 19 h, were characterized by a wide range of WSOCp and
      water vapor concentrations. Several hypotheses for the correlation are explored,
      including heterogeneous liquid phase SOA formation and the co-emission of
      biogenic VOCs and water vapor. The data provide supporting evidence for
      contributions from both and suggest the possibility of a synergistic effect
      between the co-emission of water vapor and VOCs from biogenic sources on SOA
      formation. Median WSOCp concentrations were also correlated with elemental carbon
      (EC), although this correlation extended over the entire summer. Despite the
      emission of water vapor from anthropogenic mobile sources and the WSOCp-EC
      correlation, mobile sources were not considered a potential cause for the WSOCp
      water vapor correlations because of their low contribution to the water vapor
      budget. Meteorology could perhaps have influenced the WSOCp-EC correlation, but
      other factors are implicated as well. Overall, the results suggest that the
      temperature-dependent co-emission of water vapor through evapotranspiration and
      SOA precursor-VOCs by vegetation may be an important process contributing to SOA
      in some environments.

PMID- 19174875
TI  - Cold-trapping of persistent organic pollutants in the mountain soils of western
      Sichuan, China.
AB  - In the Chinese province of Sichuan steep mountains rise from the very densely
      populated and intensely cultivated Chengdu basin more than 4000 elevational
      meters to the Tibetan Plateau. This steep physical gradient is exceptionally well
      suited to investigate the transport of persistent pesticides and other organic
      contaminants from low to high elevations. In spring and autumn 2006, 25 soil
      samples were taken at five elevations ranging from 2636 to 4479 m along the East
      facing slope of Balang Mountain in Wolong Nature Reserve. Analysis of soil
      extracts was done by gas chromatography-high resolution mass spectrometry.
      Whereas hexachlorobenzene (HCB), hexachlorocyclohexanes (HCH), and
      dichlorodibenzotrichloroethane and its degradation products (DDTs) were present
      at levels of a few ng/g, only two light PCB congeners were detected at levels
      below 1 ng/g in soil. Soil concentration for all analytes increased significantly
      and exponentially with altitude. The rate of concentration increase, expressed
      quantitatively through the slope of the linear regression between the logarithm
      of the concentrations and altitude, increases along the sequence HCB < PCB < HCH
      < or = DDT. This trend is consistent with, and therefore lends additional
      observational support to, a mountain cold-trapping mechanism based on the
      temperature dependence of precipitation scavenging.

PMID- 19174876
TI  - On the mechanism of mountain cold-trapping of organic chemicals.
AB  - The preferential accumulation of selected organic pollutants at higher altitude
      has been observed in a number of mountain regions. It is proposed that this
      phenomenon is due to differences in the efficiency of precipitation scavenging at
      various elevations, which, in turn, is due to the temperature dependence of
      organic vapor partitioning into rain, snow, and aerosols. The occurrence and
      extent of enrichment with elevation depends on whether the scavenging efficiency
      of a chemical is sensitive to temperature within the range encountered along a
      mountain slope. A multicompartment fate and transport model parameterized for
      mountain systems suggeststhat substances with equilibrium partitioning
      coefficients at 25 degrees C between water and air from 10(3.5) to 10(5.5) and
      between atmospheric particles and air from 10(9) to 10(11) are most likely to be
      subject to mountain cold-trapping. Such substances remain in the atmospheric
      vapor phase at higher valley temperatures, but are scavenged efficiently at the
      lower temperatures prevailing at higher altitudes. This implies that substances
      subject to mountain cold-trapping are approximately 2 orders of magnitude less
      volatile than substances that experience global cold-trapping. For example, while
      lighter PCBs get preferentially trapped at higher latitudes, the heavier PCBs are
      predicted to experience the strongest mountain cold-trapping. These model results
      agree with the results of field studies, with the exception of those studies that
      rely on sample media such as plant foliage for which precipitation is not the
      dominant deposition pathway. It appears that very fast deposition processes are
      required to trap contaminants along mountain slopes, whereas such processes
      reduce contaminant transport to remote polar regions.

PMID- 19174877
TI  - Interactions among K+-Ca2+ exchange, sorption of m-dinitrobenzene, and smectite
      quasicrystal dynamics.
AB  - The fate of organic contaminants in soils and sediments is influenced by sorption
      of the compounds to surfaces of soil materials. We investigated the interaction
      among sorption of an organic compound, cation exchange reactions, and both the
      size and swelling of smectite quasicrystals. Two reference smectites that vary in
      location and amount of layer charge, SPV (a Wyoming bentonite) and SAz-1 were
      initially Ca- and K-saturated and then equilibrated with mixed 0.01 M KCl and
      0.005 M CaCl2 salt solutions both with and without the presence of 200 mg L(-1) m
      dinitrobenzene (m-DNB). In general, sorption of m-DNB increased with the amount
      of K+ in the system for both clays, and the SPV sorbed more m-DNB than the SAz-1.
      Sorption of m-DNB increased the preference of Ca-SPV for K+ relative to Ca2+ but
      had little effect on K+-Ca2+ selectivity for K-SPV. Selectivity for K+ relative
      to Ca2+ was slightly higher for both K-SAz-1 and Ca-SAz-1 in the presence of m
      DNB than in its absence. Distinct hysteresis loops were observed for the K+-Ca2+
      cation exchange reactions for both clays, and the legacy of having been initially
      Ca- or K-saturated influenced sorption of m-DNB by SPV but had little effect for
      SAz-1. Suspension X-ray diffraction was used to measure changes in d-spacing and
      the relative thickness of smectite quasicrystals during the cation exchange and m
      DNB sorption reactions. The results suggest that interactions among cation
      exchange and organic sorption reactions are controlled byan inherently hysteretic
      complex feedback process that is regulated by changes in the size and extent of
      swelling of smectite quasicrystals.

PMID- 19174878
TI  - A significant downturn in levels of hexabromocyclododecane in the blubber of
      harbor porpoises (Phocoena phocoena) stranded or bycaught in the UK: an update to
      2006.
AB  - In an earlier paper, we reported data indicating a sharp increase in
      hexabromocyclododecane concentrations in the blubber of 85 harbor porpoises from
      the UK, from about 2001 onward. That time trend was evaluated using data from
      1994-2003, generated on a diastereoisomer basis using LC-MS. In this paper we
      report additional data for 138 animals collected during 2003-2006. SigmaHBCD
      concentrations ranged from <10 to 11,500 microg kg(-1) wet weight (up to 12,800
      microg kg(-1) lipid weight) and TBBP-A was not detected in any samples. The
      maximum SigmaHBCD concentration observed in this study was about half that seen
      in the earlier study (21,400 microg kg(-1) lipid weight) and, in both studies,
      the highest concentration was for an animal stranded or bycaught in 2003.
      Investigation of time trends confirmed a statistically significant increase
      between 2000 and 2001 (p < 0.01) and a statistically significant decrease between
      2003 and 2004 (p < 0.05). Neither trend was confounded by age, sex, nutritional
      status, or location. Possible contributory factors to the observed decrease
      include the closure in 2003 of an HBCD manufacturing plant in NE England which
      had considerable emissions up to 2003, and two voluntary schemes intended to
      reduce emissions of HBCD to the environment from industry which, however, did not
      formally begin until 2006.

PMID- 19174879
TI  - Metamorphosis in chironomids, more than mercury supply, controls methylmercury
      transfer to fish in High Arctic lakes.
AB  - Lake-dwelling Arctic char (Salvelinus alpinus) are monitored internationally as a
      sentinel species for effects of atmospheric mercury deposition on Arctic fresh
      waters. We investigated the control of mercury supply and biological processes on
      the methylmercury (MeHg) content of their main food, aquatic chironomids, in 22
      lakes and ponds in the Canadian High Arctic. Total mercury (THg) concentrations
      in sediment (corrected for organic matter content) increased with drainage basin
      size, suggesting a gradient in mercury loading among study sites. MeHg
      concentrations in sediment and water were low and relatively uniform along this
      THg supply gradient suggesting MeHg production in High Arctic lakes is weakly
      coupled to inorganic mercury supply. Metamorphosis was a key biological process
      that concentrated MeHg in adult chironomids 1.7-2.9 times more than in immature
      stages. Drainage basin size, environmental mercury levels, and habitat
      characteristics were also significant factors but they explained less variation
      in chironomid MeHg concentration than their degree of maturity. Chironomid
      larvae, pupae, and adults are distinct mercury sources for fish, and we provide
      evidence from nitrogen stable isotopes and published feeding studies that suggest
      differential consumption of these stages may affect MeHg uptake by Arctic char.
      We conclude that biological and food web processes have a greater impact on MeHg
      transfer to fish than atmospheric mercury deposition in High Arctic lakes.

PMID- 19174880
TI  - Important source of marine secondary organic aerosol from biogenic amines.
AB  - Relevant concentrations of dimethyl- and diethylammonium salts (DMA+ and DEA+)
      were measured in submicrometer marine aerosol collected over the North Atlantic
      during periods of high biological activity (HBA) in clean air masses (median
      concentration (minimum-maximum)=26(6-56) ng m(-3)). Much lower concentrations
      were measured during periods of low biological activity (LBA): 1 (<0.4-20) ng m(
      3) and when polluted air masses were advected to the sampling site: 2 (<0.2-24)
      ng m(-3). DMA+ and DEA+ are the most abundantorganic species, second only to MSA,
      detected in fine marine particles representing on average 11% of the secondary
      organic aerosol (SOA) fraction and a dominant part (35% on average) of the water
      soluble organic nitrogen (WSON). Several observations support the hypothesis that
      DMA+ and DEA+ have a biogenic oceanic source and are produced through the
      reaction of gaseous amines with sulfuric acid or acidic sulfates. Moreover, the
      water-soluble fraction of nascent marine aerosol particles produced by bubble
      bursting experiments carried out in parallel to ambient aerosol sampling over the
      open ocean showed WSON, DMA+, and DEA+ concentrations always below the detection
      limit, thus excluding an important primary sea spray source.

PMID- 19174881
TI  - Contemporary or fossil origin: split of estimated secondary organic carbon in the
      southeastern United States.
AB  - One year of high-volume PM2.5 filter samples were collected from 2004 to 2005 at
      one rural site and three urban sites in the Southeastern Aerosol Research and
      Characterization (SEARCH) network. These filters were analyzed for both organic
      tracers and carbon isotopes. Sources for primary carbon were previously
      apportioned based on molecular marker-based chemical mass balance modeling (CMB
      MM). In this study, these primary sources were further classified into two
      categories as having fossil and contemporary origins. 14C data were used to
      estimate the relative contributions of fossil and contemporary contents in total
      carbon (TC). Combined these two sets of independent results, fossil and
      contemporary contributions to secondary carbon source, which was estimated by the
      unexplained OC in CMB-MM, were calculated. The fossil secondary organic carbon
      (SOCF) and the contemporary secondary organic carbon (SOCC) ranged from 0.56 to
      3.20 microgC/m3 and 0.82 to 4.09 microgC/m3, respectively. SOCF was higher at
      urban sites and exhibited small seasonal variation at all sites, probably
      resulting from higher fossil precursor emissions in urban areas. In contrast,
      SOCC was higher at the rural site and exhibited obvious seasonal variation at all
      sites. During the whole year SOCF was the major secondary organic carbon (SOC)
      contributor at the urban sites, while SOCC dominated SOC at the rural site. In
      summer isoprene-derived SOC showed a large contribution to SOCC and exhibited
      significant positive correlation with SOCC, indicating the importance of isoprene
      derived secondary organic aerosol (SOA) formation during summer. It is
      interesting to note that the secondary items, including SOCF, SOCC, secondary
      sulfate, and secondary ammonium, exhibited significant correlations between the
      monitoring sites, suggesting the regional impact of secondary aerosol in the
      southeastern United States.

PMID- 19174882
TI  - Mutual influences between natural organic matter and inorganic particles and
      their combined effect on ultrafiltration membrane fouling.
AB  - Fouling is one of the most critical aspects of membrane technology and is
      strongly influenced by natural water characteristics.This studyfocuses on a
      mechanistic understanding of the impact of interactions between natural organic
      matter (NOM) and particles on fouling. The model substances used were humic acid,
      alginate (polysaccharide), and kaolinite. NOM-kaolinite adsorption experiments,
      particle characterization, and dead-end ultrafiltration (UF) batch experiments
      were performed. The adsorption experiments indicated particle stabilization at
      low NOM equilibrium concentrations, whereas calcium induced significant
      aggregation, especially with alginate. UF experiments implicated a synergistic
      fouling effect of particle-NOM combinations, which was greatly reduced by
      calcium. Moreover, irreversible NOM fouling was only prevented by particles in
      the presence of calcium. On the basis of our results, we present a mechanistic
      model suggesting that synergistic fouling effects occur due to particle
      stabilization by NOM adsorption, especially shown for HA, and antagonistic
      effects due to particle destabilization by calcium. However, synergistic fouling
      can also be based on sterical interferences between larger NOM in the form of
      polysaccharides and particles during simultaneous pore blocking and cake
      formation. A heterogeneous NOM-particle fouling layer is ultimately formed with
      membrane associations dominated by NOM. The combined fouling is conclusively
      determined bythe type of NOM, its specific fouling mechanisms, and its particle
      interactions prior to and during the filtration process.

PMID- 19174873
TI  - Changes in microbial community structure in the wake of Hurricanes Katrina and
      Rita.
AB  - Hurricanes have the potential to alter the structures of coastal ecosystems and
      generate pathogen-laden floodwaters thatthreaten public health. To examine the
      impact of hurricanes on urban systems, we compared microbial community structures
      in samples collected after Hurricane Katrina and before and after Hurricane Rita.
      We extracted environmental DNA and sequenced small-subunit rRNA (SSU rRNA) gene
      clone libraries to survey microbial communities in floodwater, water, and
      sediment samples collected from Lake Charles, Lake Pontchartrain, the 17th Street
      and Industrial Canals in New Orleans, and raw sewage. Correspondence analysis
      showed that microbial communities associated with sediments formed one cluster
      while communities associated with lake and Industrial Canal water formed a
      second. Communities associated with water from the 17th Street Canal and
      floodwaters collected in New Orleans showed similarity to communities in raw
      sewage and contained a number of sequences associated with possible pathogenic
      microbes. This suggests that a distinct microbial community developed in
      floodwaters following Hurricane Katrina and that microbial community structures
      as a whole might be sensitive indicators of ecosystem health and serve as
      "sentinels" of water quality in the environment.

PMID- 19174883
TI  - Release of Pb(II) from monochloramine-mediated reduction of lead oxide (PbO2).
AB  - A contributing factor causing the sudden release of excessive lead into drinking
      water is believed to involve the change in redox conditions occurring when
      monochloramine (NH2Cl) replaces free chlorine as a disinfectant. Studies suggest
      that NH2Cl cannot effectively oxidize Pb(II) to form PbO2, a Pb(IV) mineral scale
      formed from the oxidation of metallic lead and Pb(II) species by free chlorine.
      Unexpectedly, we observed that NH2Cl is actually capable of reducing PbO2 to form
      Pb(II). We systematically investigated this reaction by varying important water
      chemistry factors such as solution pH, total carbonate concentration, and the
      Cl/N molar ratio to control chloramine speciation and its rate of decomposition
      via a complex set of autodecomposition reactions. The amount of Pb(II) formed was
      found to be proportional to the amount of NH2Cl that autodecomposed regardless of
      the rate of this reaction. This implies thatthe rate of Pb(II) release is
      proportional to the absolute rate of NH2CI decomposition. It is proposed that the
      species responsible for the reduction of PbO2 is likely a reactive intermediate
      produced during the decay of NH2Cl. This finding is the first to report that
      NH2Cl can act as a reductant.

PMID- 19174884
TI  - The contribution of anammox and denitrification to sediment N2 production in a
      surface flow constructed wetland.
AB  - This study used anaerobic slurry assays and intact core incubations to quantify
      potential rates of anammox (anaerobic ammonia oxidation) in sediments along the
      flow path of a surface flow constructed wetland receiving secondary treated
      sewage effluent. Anammox occurred at two of the four sites assayed with a maximum
      rate of 199.4 +/- 18.7 micromol N x m(-2) x hr(-1) (24% of total N2 production)
      at the discharge end of the wetland. Denitrification was the major producer of
      N2, with a maximum rate of 965.3 +/- 122.8 micromol N x m(-2) x hr(-1) at site 2.
      Oxygen was probably the key regulator of anammox activity within the studied CW.
      In addition to anammox, we found evidence that nitrifier-denitrification was
      potentially responsible for the production of N2O. Total production of N2O was
      15.1% of the total gaseous N produced. Limitations to the methodology for
      quantifying anammox in CW's are outlined. This study demonstrated that
      denitrification is not the only pathway for gaseous production in constructed
      wetlands and that wetlands may be significant sources of greenhouse gases such as
      N2O.

PMID- 19174885
TI  - Norovirus removal and particle association in a waste stabilization pond.
AB  - The presence of norovirus (NoV) genogroup I (GI) and II (GII) was evaluated using
      real-time reverse transcription polymerase chain reaction (rRT-PCR) in the
      influent, two midtreatment locations, and final effluent of a three-pond serial
      waste stabilization pond system from December 2005 through June 2006.
      Additionally, influent and effluent samples were filtered through a cascade of
      three membrane filters with sequentially smaller pores to determine the size
      range of particles with which GI and GII were associated. NoV GI and GII removal
      occurs primarily in the third pond. Viruses were found on large settleable
      particles (retained on a 180 microm filter), on smaller suspended particles
      (retained on a 0.45 microm filter), on colloidal particles (retained on a
      positively charged 0.45 microm filter), and in the final filtrate. Both GI and
      GII in influent samples were found to be dominantly associated with particles
      smaller than 180 microm, thereby suggesting that particle settling is not the
      main virus removal mechanism in the waste stabilization pond system. On average,
      NoV detected in filtered effluent samples were associated with particles between
      0.45 and 180 microm in diameter (47 and 67% of detected GI and GII,
      respectively). The presence of NoV GI and GII in the final filtrate of influent
      and effluent samples shows that positively charged membrane filters often used
      for viral concentration methods are not capable of trapping all viruses present
      in wastewater samples.

PMID- 19174886
TI  - Depleted uranium mobility across a weapons testing site: isotopic investigation
      of porewater, earthworms, and soils.
AB  - The mobility and bioavailability of depleted uranium (DU) in soils at a UK
      Ministry of Defence (UK MoD) weapons testing range were investigated. Soil and
      vegetation were collected near a test-firing position and at eight points along a
      transect line extending approximately 200 m down-slope, perpendicular to the
      firing line, toward a small stream. Earthworms and porewaters were subsequently
      separated from the soils and both total filtered porewater (<0.2 microm) and
      discrete size fractions (0.2 microm-100 kDa, 100-30 kDa, 30-3 kDa, and <3
      kDa)obtainedvia centrifugal ultrafiltration were examined. Uranium concentrations
      were determined by inductively coupled plasma optical emission spectrometry (ICP
      OES) for soils and ICP-mass spectrometry (MS) for earthworms and porewaters,
      while 235U:238U atom ratios were determined by multicollector (MC)-ICP-MS.
      Comparison of the porewater and earthworm isotopic values with those of the soil
      solids indicated that DU released into the environment during weapons test-firing
      operations was more labile and more bioavailable than naturally occurring U in
      the soils at the testing range. Importantly, DU was shown to be present in soil
      porewater even at a distance of approximately 185 m from the test-firing position
      and, along the extent of the transect was apparently associated with organic
      colloids.

PMID- 19174887
TI  - Multiphase chemistry of ozone on fulvic acids solutions.
AB  - By means of a wetted-wall flow tube, we studied the multiphase chemistry of ozone
      on aqueous solutions containing fulvic acids (FA), taken as proxies for
      atmospheric "humic like substances", so-called HULIS. In these experiments, the
      loss of gaseous O3 was monitored by UV-visible absorption spectroscopy at the
      reactor outlet (i.e., after contact between the gaseous and liquid phases).
      Measurements are reported in terms of dimensionless uptake coefficients (gamma)
      in the range from 1.6 x 10(-7) to 1.3 x 10(-5) depending on ozone gas phase
      concentration (in the range from 6.6 to 34.4 x 10(11) molecules cm(-3)) and
      fulvic acid aqueous concentration (in the range from 0.25 to 2.5 mg L(-1)) and pH
      (in the range from 2.5 to 9.2). The measured kinetics were observed to follow a
      Langmuir-Hinshelwood type mechanism, in which O3 first adsorbs on the liquid
      surface and then reacts with the Fulvic Acid molecules. The reported uptake
      coefficients are greatly increased over those measured on pure water,
      demonstrating that the presence in solution of fulvic acids does greatly enhance
      the uptake kinetics. Accordingly, the chemical interactions of fulvic acids (or
      HULIS) may be a driving force for the uptake of ozone on liquid organic aerosols
      and can also represent an important mechanism for the O3 deposition to the rivers
      and lakes.

PMID- 19174888
TI  - Mercury stable isotope fractionation during reduction of Hg(II) by different
      microbial pathways.
AB  - Mercury (Hg) stable isotope fractionation has recently been developed as a tool
      in biogeochemistry. In this study, the extent of Hg stable isotope fractionation
      during reduction of ionic mercury [Hg(II)] by two Hg(II)-resistant strains,
      Bacillus cereus 5 and the thermophile Anoxybacillus sp. FB9 [which actively
      detoxify Hg(II) by the mer system] and a Hg(II)-sensitive metal-reducing
      anaerobe, Shewanella oneidensis MR-1 [which reduces Hg(II) at low
      concentrations], was investigated. In all cases, barring suppression of
      fractionation that is likely due to lower Hg(II) bioavailability, the Hg(II)
      remaining in the reactor became progressively enriched with heavy isotopes with
      time and underwent mass-dependent Rayleigh fractionation with alpha202/198 values
      of 1.0016 +/- 0.0004 (1 SD). Based on a multistep framework for the Hg(II)
      reduction pathways in the three strains, we constrain the processes that could
      contribute toward fractionation and suggest that for Hg(II)-resistant strains,
      reduction by mercuric reductase is the primary step causing fractionation. The
      proposed framework helps explain the variation in the extent of Hg stable isotope
      fractionation during microbial reduction of Hg(II), furthering the promise of Hg
      isotope ratios as a tool in determining the role of microbial Hg transformations
      in the environment.

PMID- 19174889
TI  - Role of oxygen tension on the transport and retention of two pathogenic bacteria
      in saturated porous media.
AB  - To examine the influence of variations in the dissolved oxygen (DO) concentration
      on pathogen mobility, laboratory-scale filtration experiments were performed
      using the enterohemorrhagic strain Escherichia coli O157:H7 and the
      enteroinvasive organism Yersinia enterocolitica. Cells were incubated either in
      the absence (anaerobic) or in the presence (aerobic) of oxygen to understand how
      these two growth conditions may affect bacterial transport and retention in water
      saturated granular porous media. The influence of DO during growth is found to be
      organism dependent, whereby E. coli O157:H7 exhibits decreased transport
      potential when grown in the presence of 02 and Y. enterocolitica exhibits greater
      transport when grown aerobically. To understand the influence of DO changes
      during cell acclimation and transport, bacteria were resuspended and acclimated
      in either oxygen-depleted (low DO) or oxygen-rich (saturated DO) electrolytes
      prior to conduction of filtration experiments. The effect of DO on bacterial
      transport and retention is shown to be dependent on the antecedent growth
      conditions and on the organism studied. Measurements of the cell surface charge,
      shape, and size reveal some variability when the oxygen tension is changed during
      bacterial growth or acclimation and are linked to the observed bacterial
      transport behavior.

PMID- 19174890
TI  - Microheterogeneous concentrations of singlet oxygen in natural organic matter
      isolate solutions.
AB  - The binding affinity of a hydrophobic singlet oxygen probe toward natural organic
      matter isolates was investigated. A linear phase-partitioning model was used to
      calculate partition coefficients and intramicellar concentrations of singlet
      oxygen several orders of magnitude larger than those reported by traditional
      singlet oxygen probes. From the obtained data, a kinetic model was developed to
      describe the microscopic environment experienced by hydrophobic compounds in
      natural water systems. Micellar radii and molecular weights were derived from the
      experimental data and evaluated. The data obtained provides additional support of
      a microheterogeneous environment within bulk natural solutions. The enhanced
      concentrations of photogenerated reactive intermediates within these
      microenvironments may improve understanding of hydrophobic pollutant degradation
      in the environment.

PMID- 19174891
TI  - In situ ATR FTIR studies of SO4 adsorption on goethite in the presence of copper
      ions.
AB  - Despite the existence of many single ion sorption studies on iron and aluminum
      oxides, fewer studies have been reported that describe cosorption reactions. In
      this work, we present an in situ ATR FTIR study of synergistic adsorption of
      sulfate (SO4) and copper (Cu) on goethite, which is representative of the
      minerals and ions present in mine wastes, acid sulfate soils, and other
      industrial and agricultural settings. Sulfate adsorption was studied as a
      function of varying pH, and as a function of increasing concentration in the
      absence and presence of Cu. The presence of Cu ions in solution had a complex
      effect on the ability of SO4 ions to be retained on the goethite surface with
      increasing pH, with complete desorption occurring near pH 7 and 9 in the absence
      and presence of Cu, respectively. In addition, Cu ions altered the balance of
      inner vs outer sphere adsorbed SO4. The solid phase partitioning of SO4 at pH 3
      and pH 5 was elevated by the presence of Cu; in both cases Cu increased the
      affinity of SO4 for the goethite surface. Complementary ex situ sorption edge
      studies of Cu on goethite in the absence and presence of SO4 revealed that the Cu
      adsorption edge shifted to lower pH (6.3 --> 5.6) in the presence of SO4,
      consistent with a decrease of the electrostatic repulsion between the goethite
      surface and adsorbing Cu. Based on the ATR FTIR and bulk sorption data we surmise
      that the cosorption products of SO4 and Cu at the goethite-water interface were
      not in the nature of ternary complexes under the conditions studied here. This
      information is critical for the evaluation of the onset of surface precipitates
      of copper-hydroxy sulfates as a function of pH and solution concentration.

PMID- 19174892
TI  - Highly charged swelling mica reduces free and extractable Cu levels in Cu
      contaminated soils.
AB  - Smelting of copper (Cu) results in the atmospheric deposition of Cu onto
      surrounding soils. Excess concentrations of Cu in soils can be absorbed by soil
      biota to toxic levels or leached into the groundwater, threatening the entire
      ecosystem. A means to restrict Cu mobility and uptake by plants is to remove it
      from the aqueous phase by applying an adsorptive material. A synthetic clay
      (highly charged swelling mica) was tested for its ability to decrease the levels
      of free and 0.1 M KNO3-extractable Cu in 15 surface soils from three different Cu
      mining areas in central Chile. The soils contained excessive total Cu levels (112
      2790 mg Cu (kg soil)(-1)), while extractable Cu ranged from 0.3 to 22.9 mg Cu L(
      1). The mica was applied to each soil at rates of 0.1%, 1%, and 2% (w/w). A 2%
      sodium-montmorillonite treatment and the nonamended soil served as controls. The
      order of treatment efficacy in reducing extractable Cu and free Cu2+ for low pH
      soils (<pH 5.5) was: 2% mica > 1% mica > 2% montmorillonite > 0.1% mica. At 120
      days, the 2% mica treatment maintained reductions of up to 93% in the free Cu2+
      activity and up to 75% in the extractable Cu concentration upon acidification to
      the original soil pH value. In addition, Cu retention in mica-treated soils was
      more resistant to acidification than in lime-treated soils. This mica has promise
      for the remediation of acidic soils with metal contamination at the surface.

PMID- 19174893
TI  - Formation of nitro products from the gas-phase OH radical-initiated reactions of
      toluene, naphthalene, and biphenyl: effect of NO2 concentration.
AB  - Aromatic hydrocarbons, including polycyclic aromatic hydrocarbons (PAHs), are
      released into the atmosphere principally during incomplete combustion and account
      for approximately 20% of nonmethane organic compounds in urban air. Reaction with
      OH radicals is the dominant atmospheric chemical loss process for aromatic
      hydrocarbons, leading mainly to the formation of an OH-aromatic or OH-PAH adduct
      which then reacts with O2 and/or NO2. For OH-monocyclic aromatic adducts,
      reaction with O2 dominates under atmospheric conditions; however, no data are
      available concerning the relative importance of reactions of OH-PAH adducts with
      O2 and NO2. We have measured formation yields of 3-nitrotoluene, 1- and 2
      nitronaphthalene, and 3-nitrobiphenyl from the OH radical-initiated reactions of
      toluene, naphthalene, and biphenyl as a function of NO2 concentration. Our data
      showthatthe OH-aromatic adduct reactions with O2 and NO2 are of equal importance
      in the atmosphere at NO2 mixing ratios of approximately 3.3 ppmV for toluene,
      approximately 0.06 ppmV for naphthalene, and approximately 0.6 ppmV for biphenyl.
      Ambient concentrations of toluene, naphthalene, and biphenyl and their nitrated
      products measured at a site in the Los Angeles air basin are consistent with our
      laboratory measurements.

PMID- 19174894
TI  - Distribution and weathering of crude oil residues on shorelines 18 years after
      the Exxon Valdez spill.
AB  - In 2007, a systematic study was conducted to evaluate the form and location of
      residues of oil buried on Prince William Sound (PWS) shorelines, 18 years after
      the 1989 Exxon Valdez Oil Spill (EVOS). We took 678 sediment samples from 22
      sites that were most heavily oiled in 1989 and known to contain the heaviest
      subsurface oil (SSO) deposits based on multiple studies conducted since 2001. An
      additional 66 samples were taken from two sites, both heavily oiled in 1989 and
      known to be active otter foraging sites. All samples were analyzed for total
      extractable hydrocarbons (TEH), and 25% were also analyzed for saturated and
      aromatic hydrocarbon weathering parameters. Over 90% of the samples from all
      sites contained light or no SSO at all. Of samples containing SSO, 81% showed
      total polycyclic aromatic hydrocarbon (TPAH) losses greater than 70%, relative to
      cargo oil, with most having >80% loss. Samples with SSO were observed in isolated
      patches sequestered by surface boulder and cobble armoring. Samples showing
      lowest TPAH loss correlated strongly with higher elevations in the intertidal
      zones. Of the 17 atypical, less-weathered samples having less than 70% loss of
      TPAH (>30% remaining), only two were found sequestered in the lower intertidal
      zone, both at a single site. Most of the EVOS oil in PWS has been eliminated due
      to natural weathering. Some isolated SSO residues remain because they are
      sequestered and only slowly affected by natural weathering processes that
      normally would bring about their rapid removal. Even where SSO patches remain,
      most are highly weathered, sporadically distributed at a small number of sites,
      and widely separated from biologically productive lower intertidal zones where
      most foraging by wildlife occurs.

PMID- 19174895
TI  - Summer E. coli patterns and responses along 23 Chicago beaches.
AB  - Concentrations of E. coli in recreational beach water are highly variable both
      locally and temporally, but a broader understanding of these fluctuations may be
      explained through coastal observations. Currently, beach contamination study
      approaches tend to be site-specific under the belief that politically delineated
      beaches are unique and management of beaches cannot be regionally oriented. E.
      coli data collected over five years from 23 Chicago beaches clearly identified
      ambient linked patterns at the regional scale. Temporal fluctuations were
      similar, with all beaches having simultaneous peaks and troughs of E. coli
      concentrations. Spatially, E. coli concentrations for beaches more closely
      situated were more closely correlated, indicating spatial autocorrelation. Julian
      day, wave height, and barometric pressure explained up to 40% of the variation, a
      value comparable to individual, less parsimonious site-specific models. Day of
      sampling could explain the majority of the variation in E. coli concentrations,
      more so than beach, depth, or time of day. Comparing beaches along a targeted
      coastline allows a better understanding of inherent background regional
      fluctuations and, ultimately, better predictions of E. coli concentrations in
      coastal recreational water.

PMID- 19174896
TI  - Modeling fallout of anthropogenic 129I.
AB  - Despite the relatively well-recognized emission rates of the anthropogenic 129I,
      there is little knowledge about the temporal fallout patterns and magnitude of
      fluxes since the start of the atomic era atthe early 1940s. We here present
      measurements of annual 129I concentrations in sediment archives from Sweden and
      Finland covering the period 1942-2006. The results revealed impression of 129I
      emissions from the nuclear reprocessing facility at Sellafield and La Hague and a
      clear Chernobyl fallout enhancement during 1986. In order to estimate relative
      contributions from the different sources, a numerical model approach was used
      taking into accountthe emission rates/estimated fallout, transport pathways, and
      the sediment system. The model outcomes suggest a relatively dominating marine
      source of 129I to north Europe compared to direct gaseous releases. A transfer
      rate of 129I from sea to atmosphere is derived for pertinent sea areas (English
      Channel, Irish Sea, and North Sea), which is estimated at 0.04 to 0.21 y(-1).

PMID- 19174897
TI  - Air-liquid partition coefficient for a diverse set of organic compounds: Henry's
      Law Constant in water and hexadecane.
AB  - The SPARC vapor pressure and activity coefficient models were coupled to
      successfully estimate Henry's Law Constant (HLC) in water and in hexadecane for a
      wide range of organic compounds without modification to, or additional
      parametrization of, either SPARC model. The vapor pressure model quantifies the
      solute-solute intermolecular interactions in the pure liquid phase, whereas the
      activity coefficient model quantifies the solute-solvent and solvent-solvent (in
      addition to the solute-solute) interactions upon placing solute, i, in solvent,
      j. These intermolecular interactions are factored into dispersion, induction,
      dipole-dipole, and H-bonding components upon moving a solute molecule from the
      gas to the liquid phase. The SPARC HLC calculator so produced was tested and
      validated on the largest experimental HLC data set to date: 1356 organic solutes,
      spanning a wide range of functional groups, dipolarities and H-bonding
      capabilities, such as PAHs, PCBs,VOCs, amides, pesticides, and pharmaceuticals.
      The rms deviation errors for the calculated versus experimental log HLCs for 1222
      compounds in water and 563 in hexadecane were 0.456 and 0.192 log
      [(mol/L)/(mol/L)] units, respectively, spanning a range of more than 13 and 20
      log HLC dimensionless units for the compounds in water and hexadecane,
      respectively. The SPARC calculator web version is available for public use, free
      of charge, and can be accessed at http://sparc.chem.uga.edu.

PMID- 19174898
TI  - Health-risk-based groundwater remediation system optimization through clusterwise
      linear regression.
AB  - This study develops a health-risk-based groundwater management (HRGM) model. The
      model incorporates the considerations of environmental quality and human health
      risks into a general framework. To solve the model, a proxy-based optimization
      approach is proposed, where a semiparametric statistical method (i.e.,
      clusterwise linear regression) is used to create a set of rapid-response and easy
      to-use proxy modules for capturing the relations between remediation policies and
      the resulting human health risks. Through replacing the simulation and health
      risk assessment modules with the proxy ones, many orders of magnitude of
      computational cost can be saved. The model solutions reveal that (i) a long
      remediation period corresponds to a low total pumping rate, (ii) a stringent risk
      standard implies a high total pumping rate, and (iii) the human health risk
      associated with benzene would be significantly reduced if it is regarded as
      constraints of the model. These implications would assist decision makers in
      understanding the effects of remediation duration and human-health risk level on
      optimal remediation policies and in designing a robust groundwater remediation
      system. Results from postoptimization simulation show that the carcinogenic risk
      would decrease to satisfy the regulated risk standard under the given remediation
      policies.

PMID- 19174899
TI  - Modeling the environmental fate of polybrominated diphenyl ethers (PBDEs): the
      importance of photolysis for the formation of lighter PBDEs.
AB  - A global multimedia model is used to calculate the fate of polybrominated
      diphenyl ethers (PBDEs) in the environment. Special emphasis is given to the
      importance of direct photolysis, which has been shown to be an important
      degradation mechanism for highly brominated PBDEs and is believed to result in
      the formation of lower-brominated PBDEs. We show that the inclusion of direct
      photolysis decreases the overall persistence and long-range transport potential
      of most PBDEs, in particular the heavier ones. We develop a PBDE emission
      inventory and calculate environmental concentrations of different PBDEs.
      Differences between predicted concentrations and field data are assessed and
      possible reasons for these differences discussed. The formation of lighter PBDEs
      by debromination of deca-BDE is compared to direct emissions of lighter PBDE
      homologues. The model estimates that about 13% of the penta-BDE and about 2% of
      the tetra-BDE homologue found in the environment arise from the degradation of
      deca-BDE. Uncertainties of the model estimates are quantified and their
      implications for the findings of our study discussed.

PMID- 19174900
TI  - Donnan effects in metal speciation analysis by DET/DGT.
AB  - Cross-linked polyacrylamide gels have found wide application in analytical
      techniques, such as diffusional equilibration in thin film (DET) and diffusive
      gradient in thin film (DGT). In these applications, the assumption is made that
      the gel matrix is effectively uncharged and chemically inert with respect to the
      species of interest. Recent data has shown significant nonideal behavior at low
      ionic strengths, which strongly suggests a finite structural charge within the
      gel matrix. The present investigation explores the possible ramifications of
      fixed charged sites within the gel on metal speciation analysis by DET and DGT.
      The results indicate that structural charge within the gel layer will give rise
      to different DET equilibrium concentrations than in the sample because of Donnan
      partitioning. The steady-state diffusion of ions through a diffusive gel (DGT) is
      also influenced by the gel charge, but the net effect will depend on the details
      of the speciation. The results indicate that for submillimolar ionic strength
      solutions the quantitative interpretation of DGT data benefits from combination
      with DET.

PMID- 19174901
TI  - Streamlined combustion gas measurements for improved national dioxin inventories.
AB  - The analysis of PCDD/Fs requires advanced analytical instruments and is a
      complex, labor intensive process that consumes large quantities of high-purity
      solvents. It is therefore very expensive and thus problematic--or even impossible
      -for developing countries to afford to establish reliable PCDD/F source
      inventories in support of global and national emission reduction strategies. Low
      cost reliable alternatives are needed to improve this situation. Therefore, a
      streamlined procedure for flue gas sampling and analysis has been developed and
      evaluated that utilizes a user-friendly polyurethane foam plug (PUFP) sampling
      technique. The collected samples are then shipped to a central laboratory for
      analysis where they are processed using a cost-efficient pressurized liquid
      extraction procedure with in-cell carbon cleanup (PLE-C) prior to analysis by gas
      chromatography--high-resolution mass spectrometry (GC-HRMS). The PLE-C technique
      has previously been validated for a range of matrices, and, in the present study,
      has been further improved by introducing an extraction cell coupling cartridge.
      The entire procedure was evaluated using three sets of samples: two from a
      laboratory-scale incinerator and one from a full-scale incinerator. The samples
      were expected to differ in PCDD/F levels and homologue patterns. Each sample was
      split and analyzed in parallel by both PLE-C and a reference procedure (Soxhlet
      extraction followed by a traditional multistep cleanup procedure, Sox-T). The
      results of analysis by PLE-C compared well with those from analysis by Sox-T. The
      difference between toxic equivalent (TEQ) values obtained using the PLE-C and
      reference technique for 11 PUFP samples ranged from -10% to +44% and the two
      techniques also yielded very similar PCDD/F homologue profiles. A principal
      component analysis (PCA) of the data showed that both methods were able to
      discriminate among the three sets of samples, thereby demonstrating that the
      between method variability was less than the between-sample variability. In
      summary, the results indicate that PUFP sampling followed by PLE-C extraction and
      cleanup provides a fast, relatively cheap, and reliable method for analysis of
      PCDD/Fs in flue gas.

PMID- 19174902
TI  - High resolution pore water delta2H and delta18O measurements by H2O(liquid)
      H2O(vapor) equilibration laser spectroscopy.
AB  - A new H2O(liquid)-H2O(vapor) pore water equilibration and laser spectroscopy
      method provides a fast way to obtain accurate high resolution deltaD and delta18O
      profiles from single core samples from saturated and unsaturated geologic media.
      The precision and accuracy of the H2O(liquid)-H2O(vapor) equilibration method was
      comparable to or better than conventional IRMS-based methods, and it can be
      conducted on geologic cores that contain volumetric water contents as low as 5%.
      Significant advantages of the H2O(liquid)-H2O(vapor) pore water equilibration
      method and laser isotopic analysis method include dual hydrogen- and oxygen
      isotope assays on single small core samples, low consumable and instrumentation
      costs, and the potential for field-based hydrogeologic profiling. A single core
      is sufficient to obtain detailed vertical isotopic depth profiles in geologic,
      soil, and lacustrine pore water, dramatically reducing the cost of obtaining pore
      water by conventional wells or physical water extraction methods. In addition,
      other inherent problems like contamination of wells by leakage and drilling
      fluids can be eliminated.

PMID- 19174903
TI  - Measurements of oxalic acid, oxalates, malonic acid, and malonates in atmospheric
      particulates.
AB  - This study systematically examined effects of analytical approaches on resultant
      concentrations of oxalic acid, oxalates, malonic acid, and malonates. Results
      demonstrated that employing separate water extraction and THF extraction is
      required to properly quantify dicarboxylic acids vs dicarboxylates using IC or GC
      MS. Applications of the recommended methods to analyze PM2.5 collected in
      Singapore showed that concentrations of oxalate ranged from 361.4 to 481.4 ng m(
      3), which were 10-14.7 times higher than that of oxalic acid. Unlike that of
      oxalates, malonate concentrations (10.5-23.4 ng m(-3)) were no more than half of
      malonic acid concentration (43.8-53.9 ng m(-3)) in PM2.5. Concentration ratios of
      oxalate-to-oxalic acid and malonate-to-malonic acid obtained from this work were
      applied to reported literature data; as a first approximation, in urban
      environments similar to that in Singapore, quantifiable oxalic acid, oxalates,
      malonic acid, and malonates in PM2.5 could range from 7.6 to 68.0, 82.2 to 732.8,
      6.3 to 150, and 1.3 to 60 ng m(-3), respectively. Because photooxidation
      properties and hygroscopicity of dicarboxylic acids can substantially differ from
      that of dicarboxylates, more studies are needed to quantify ambient oxalic acid
      and malonic acid vs oxalates and malonates.

PMID- 19174904
TI  - Effect of fuel and lube oil sulfur on the performance of a diesel exhaust gas
      continuously regenerating trap.
AB  - The continuously regenerating trap (CRT) is a diesel exhaust emission control
      that removes nearly all diesel particulate matter on a mass basis, but under some
      circumstances oxidation of sulfur leads to the formation of nanoparticles. The
      objective of the four year study was to determine CRT performance under
      controlled, real-world, on-road conditions, and to develop quantitative
      relationships between fuel and lubrication oil sulfur concentration and particle
      number exhaust emissions. It was shown that nanoparticle emissions are minimized
      by the use of ultralow sulfur fuels and specially formulated low sulfur
      lubrication oil. Nanoparticle emissions increased with higher exhaust
      temperatures. Fuel and lubrication oil sulfur increased the particle
      concentration by, on average, 36 x 10(6) and 0.14 x 10(6) part/cm3 for each 1 ppm
      increase in sulfur. On the other hand there was a decrease in nanoparticle
      emissions by the CRT as the system aged.

PMID- 19174905
TI  - Experimental pKa determination for perfluorooctanoic acid (PFOA) and the
      potential impact of pKa concentration dependence on laboratory-measured
      partitioning phenomena and environmental modeling.
AB  - An accurately measured equilibrium acid dissociation constant (pKa) is essential
      for understanding and predicting the fate of perfluorocarboxylic acids (PFCAs) in
      the environment. The aqueous pKa of perfluorooctanoic acid (PFOA) has been
      determined potentiometrically using a standard water-methanol mixed solvent
      approach and was found to be 3.8 +/- 0.1. The acidity of PFOA is thus
      considerably weaker than its shorter-chain PFCA homologues. This was attributed
      to differences in molecular and electronic structure, coupled with solvation
      effects. The pKa of PFOA was suppressed to approximately 2.3 at higher
      concentrations because of the aggregation of perfluorooctanoate (PFO). Often,
      PFCA partion coefficients are determined at concentrations above those found in
      the environment. Thus, it was suggested that a pKa correction factor, which
      accounts for this concentration-dependent shift in acid/base equilibrium, should
      be applied to PFCA partition efficients before they are implemented in
      environmental fate models. A pKa of 3.8 +/- 0.1 suggests that a considerable
      concentration of the PFCA exists as the neutral species in the aqueous
      environment for example, in typical Ontario rainwater, it is approximately 17%.
      Transport, fate, and partitioning models have often ignored the presence this
      species completely. The environmental dissemination of PFCAs could, in part, be
      explained by considering the role of the neutral species.

PMID- 19174906
TI  - Conditional affinity spectra of Pb2+-humic acid complexation from data obtained
      with AGNES.
AB  - The new electroanalytical technique AGNES (Absence of Gradients and Nernstian
      Equilibrium Stripping) has been applied to follow Pb2+ complexation to Purified
      Aldrich Humic Acid. A refined methodology of AGNES, allowing considerably larger
      gains, reached free metal ion concentrations down to subnanomolar values in a
      reasonable deposition time due to the lability and mobility of these complexes.
      Further insights into the meaning of the binding data, fitted to a NICA (Non
      Ideal Competitive Adsorption) isotherm, can be obtained with the concept of
      conditional affinity spectrum (CAS). For this purpose, we present the analytical
      expression for the CAS of NICA isotherm and show the CAS distributions for the Pb
      binding at fixed pH. Results reveal that the underlying spectra of each
      elementary distribution of the bimodal NICA evolve with pH yielding different
      overlapping and nonsymmetrical distributions. A non-negligible occupation of
      phenolic and carboxylic sites by Pb2+ takes place in the range of 4 < pH < 9.

PMID- 19174907
TI  - Compatibility of polymers and chemical oxidants for enhanced groundwater
      remediation.
AB  - Polymer floods provide a promising method to more effectively deliver
      conventional groundwater treatment agents to organic contaminants distributed
      within heterogeneous aquifer systems. Combinations of nontoxic polymers (xanthan
      and hydrolyzed polyacrylamide) and common chemical oxidants (potassium
      permanganate and sodium persulfate) were investigated to determine the
      suitability of these mixtures for polymer-enhanced in situ chemical oxidation
      applications. Oxidant demand and solution viscosity were utilized as initial
      measures of chemical compatibility. After 72 h of reaction with both test
      oxidants, solution viscosities in mixtures containing hydrolyzed polyacrylamide
      were decreased by more than 90% (final viscosities approximately 2 cP), similar
      to the 95% viscosity loss (final viscosities approximately 1 cP, near that of
      water) observed in xanthan/persulfate experiments. In contrast, xanthan solutions
      exposed to potassium permanganate preserved 60-95% of initial viscosity after 72
      h. Permanganate depletion in xanthan-containing experiments ranged from 2% to 24%
      over the same test period. Although oxidant consumption in xanthan/permanganate
      solutions appeared to be correlated with increasing xanthan concentrations,
      solutions of up to 2000 mg/L xanthan did not inhibit permanganate from oxidizing
      a dissolved-phase test contaminant (tetrachloroethene, PCE) in xanthan solution.
      These advantageous characteristics (high viscosity retention, moderate oxidant
      demand, and lack of competitive effects on PCE oxidation rate) render
      xanthan/permanganate the most compatible polymer/oxidant combination of those
      tested for remediation by polymer-enhanced chemical oxidation.

PMID- 19174908
TI  - Concurrent ethene generation and growth of Dehalococcoides containing vinyl
      chloride reductive dehalogenase genes during an enhanced reductive dechlorination
      field demonstration.
AB  - Dehalococcoides bacteria that produce catabolic vinyl chloride (VC) reductive
      dehalogenase enzymes have been implicated as a requirement for successful
      biological dechlorination of VC to ethene in groundwater systems. Therefore, the
      functional genes in Dehalococcoides that produce VC reductase (e.g., vcrA) may be
      important biomarkers for predicting and monitoring the performance of
      bioremediation systems treating chloroethenes via enhanced reductive
      dechlorination (ERD). As part of an ERD field demonstration, 45 groundwater
      samples were analyzed for vcrA using quantitative PCR. The demonstration
      delivered lactate continuously via groundwater recirculation over 201 days to an
      aquifer contaminated with cis-1,2-dichloroethene (cDCE, approximately 150 microM)
      and VC (approximately 80 microM). Ethene (approximately 4 microM) and
      Dehalococcoides containing vcrA (average concentration of 4 x 10(3) gene copies
      L(-1)) were detected a priori in the demonstration plot; however, aquifer
      materials in a bench treatability test were able to dechlorinate cDCE with only a
      4-month lag period. Given the short (7-month) schedule for the field
      demonstration, the field plot was bioaugmented on Day 69 with a mixed culture (KB
      1) that included Dehalococcoides containing vcrA. Stimulated ethene generation
      commenced within four weeks of donor addition. Ethene concentrations increased
      until Day 145, and reached maximum concentrations of 10-25 microM. Concentrations
      of vcrA increased concurrently with ethene production until Day 145, and
      plateaued thereafter at 10(7) to 10(8) gene copies L(-1). These results indicate
      simultaneous growth of Dehalococcoides containing vcrA and ethene generation in
      an ERD field application. The quantitative increase in concentrations of
      Dehalococcoides containing vcrA at this site provides further evidence that the
      vcrA gene is an effective biomarker for field-scale ERD systems.

PMID- 19174909
TI  - Antecedent growth conditions alter retention of environmental Escherichia coli
      isolates in transiently wetted porous media.
AB  - The physical transport of Escherichia coli in terrestrial environments may
      require control to prevent its dissemination from potential high-density sources,
      such as confined animal feedlot operations. Biobarriers, wherein convective flows
      carrying pathogens pass through a porous matrix with high retentive capacity, may
      present one such approach. Eight environmental E. coli isolates were selected to
      conduct operational retention tests (ORT) with potential biobarrier materials
      Pyrax or dolomite, or silica glass as control. The conditions in the ORT were
      chosen to simulate conditioning by manure solutes, a pulse application of a
      bacterial load followed by rainfall infiltration, and natural drainage. Removal
      was limited, and likely caused by the relatively high velocities during drainage,
      and the conditioning of otherwise favorable adhesion sites. Flagella-mediated
      motility showed the strongest correlation to biobarrier retention. Significant
      variability was observed across the E. coli isolates, but consistently higher
      retention was observed for cells with external versus intestinal pregrowth
      histories. E. coli O157:H7 was retained the least with all examined matrices,
      while E. coli K-12 displayed moderate retention and may not serve as
      representative model strain. Pyrax is a good candidate biobarrier material given
      its superior removal ability across the tested E. coli strains.

PMID- 19174910
TI  - Concomitant adsorption and desorption of organic vapor in dry and humid air
      streams using microwave and direct electrothermal swing adsorption.
AB  - Industrial gas streams can contain highly variable organic vapor concentrations
      that need to be processed before they are emitted to the atmosphere. Fluctuations
      in organic vapor concentrations make it more difficult to operate a biofilter
      when compared to a constant vapor concentration. Hence, there is a need to
      stabilize the concentration of rapidly fluctuating gas streams for optimum
      operation of biofilters. This paper describes new concomitant adsorption
      desorption (CAD) systems used with variable organic vapor concentration gas
      streams to provide the same gas stream, but at a user-selected constant vapor
      concentration that can then be more readily processed by a secondary air
      pollution control device such as a biofilter. The systems adsorb organic vapor
      from gas streams and simultaneously heat the adsorbent using microwave or direct
      electrothermal energy to desorb the organic vapor at a user-selected set-point
      concentration. Both systems depicted a high degree of concentration stabilization
      with a mean relative deviation between set-point and stabilized concentration of
      0.3-0.4%. The direct electrothermal CAD system was also evaluated to treat a
      humid gas stream (relative humidity = 85%) that contained a variable organic
      vapor concentration. The high humidity did not interfere with CAD operation as
      water vapor did not adsorb but penetrated through the adsorbent These results are
      important because they demonstrate the ability of CAD to effectively dampen
      concentration fluctuation in gas streams.

PMID- 19174911
TI  - Effects of alkyl chain branching on the biotransformation of naphthenic acids.
AB  - The rapid expansion of the oil sands industry has seen a concomitant expansion of
      the production of associated waste containing toxic naphthenic acids (NAs).
      Bioremediation of such waste is thus an important goal, but the mechanisms of
      biodegradation are still poorly understood, despite recent advances. Many oil
      sands NAs are resistant to biodegradation, and alkyl side chain branching has
      been invoked as an explanation. To investigate this hypothesis we examined the
      biotransformation by a sedimentary bacterial community of novel, synthetic,
      surrogate NAs (butylcyclohexylbutanoic acids (BCHBAs)) with variously branched
      butyl side chains (n- through t-) and unbranched alkanoate groups, plus one (4
      (4'-isobutylcyclohexyl)pentanoic acid (iso-BCHPA)), with both branched butyl and
      branched alkanoate chains. Sediment microbial populations were inoculated into
      media containing the individual surrogate NAs, and gas chromatography-mass
      spectrometry (GC-MS) was used to determine the extent of biotransformation.
      Biotransformation decreased as NA side chain branching increased. For example,
      over 97% of the n-BCHBA with the nonbranched alkyl side chain was transformed in
      30 days compared to the tert-BCHBA with the most highly branched side chain where
      only 2.5% was transformed. Both the iso-BCHBA and sec-BCHBA had intermediate
      transformation rates with about 77% and 47% transformed respectively after 30
      days. The metabolites were identified as butylcyclohexylethanoic acids in each
      case, indicating beta-oxidation of the alkanoate substituents. The iso-BCHPA with
      both chains branched was resistant to degradation. The results are thus
      consistent with earlier hypotheses for the resistance of oil sands NAs.
      Identification of bacteria capable of oxidizing such branched alkyl chains-or of
      attacking the cyclic rings of NAs, may be important if bioremediation of oil
      sands NAs is to be achieved.

PMID- 19174912
TI  - Ozonation of source-separated urine for resource recovery and waste minimization:
      process modeling, reaction chemistry, and operational considerations.
AB  - Bench-scale, semibatch experiments were performed to examine physical-chemical
      constraints on ozone (O3) absorption and micropollutant oxidation during
      ozonation of source-separated hydrolyzed urine and the concentrate and diluate
      streams produced via electrodialysis of hydrolyzed urine. O3 consumption by each
      matrix was found to occur within a fast pseudo-first-order kinetic regime.
      Critical constraints on micropollutant oxidation were found through mass transfer
      modeling to be (i) micropollutant diffusion from the bulk solution into the gas
      liquid interfacial film for compounds recalcitrant toward O3 (i.e., k"O3,app < or
      = 10(3) M(-1) s(-1)), and (ii) aqueous-phase mixing for compounds highly reactive
      toward O3 (i.e., k"O3,app > 10(3) M(-1) s(-1)). Homogeneous chemical reaction
      modeling indicated that aqueous reaction chemistry is significantly influenced
      bythe degree to which incidentally produced hydroxyl radicals are consumed by NH3
      in each matrix, in terms of (a) micropollutant oxidation efficiencies, and (b)
      potential yields of oxidation byproducts. On the basis of the experimental data
      reported here, per capita energy requirements were estimated for treatment of
      source-separated urine via (1) ozonation, (2) ozonation with postelectrodialysis,
      and (3) electrodialysis with postozonation. These estimates indicate that
      scenario (1) would likely be less energy efficient than ozonation of municipal
      wastewater effluent in achieving equivalent reductions in urine-derived
      micropollutant loads, whereas scenarios (2 and 3) could be more efficient than
      equivalent centralized wastewater treatment strategies in achieving equivalent
      levels of urine-derived nutrient and micropollutant attenuation. Furthermore,
      experimental and model data suggest that urine ozonation efficiency may be
      substantially improved by optimizing aqueous-phase mixing and specific gas-liquid
      interfacial area.

PMID- 19174913
TI  - Model predictions of realgar precipitation by reaction of As(III) with synthetic
      Mackinawite under anoxic conditions.
AB  - This study investigates the removal of As(III) from solution using mackinawite, a
      nanoparticulate reduced iron sulfide. Mackinawite suspensions (0.1-40 g/L)
      effectively lower initial concentrations of 1.3 x 10(-5) M As(III) from pH 5-10,
      with maximum removal occurring under acidic conditions. Based on Eh measurements,
      it was found that the redox state of the system depended on the mackinawite
      solids concentration and pH. Higher initial mackinawite concentrations and
      alkaline pH resulted in a more reducing redox condition. Given this, the pH edge
      data were modeled thermodynamically using pe (-log[e(-)]) as a fitting parameter
      and linear pe-pH relationships within the range of measured Eh values as a
      function of pH and mackinawite concentration. The model predicts removal of
      As(III) from solution by precipitation of realgar with the formation of secondary
      oxidation products, greigite or a mixed-valence iron oxide phase, depending on
      pH. This study demonstrates that mackinawite is an effective sequestration agent
      for As(III) and highlights the importance of incorporating redox into models
      describing the As-Fe-S-H2O system.

PMID- 19174914
TI  - Understanding reductive dechlorination of trichloroethene on boron-doped diamond
      film electrodes.
AB  - This research investigated reduction of trichloroethylene (TCE) at boron-doped
      diamond (BDD) film cathodes using a rotating disk electrode reactor. Rates of TCE
      reduction were determined as functions of the electrode potential and TCE
      concentration over a temperature range between 2 and 32 degrees C. Reduction of
      TCE resulted in production of acetate and chloride ions with no detectable
      intermediate products. At a current density of 15 mA/cm2 and concentrations below
      0.75 mM, reaction rates were first order with respect to TCE concentration, with
      surface area normalized rate constants 2 orders of magnitude greater than those
      for iron electrodes. Density functional theory (DFT) simulations were used to
      evaluate activation barriers for reduction by direct electron transfer, and for
      reaction with four functional groups commonly found on BDD surfaces. The DFT
      calculated activation barrier for direct electron transfer was more than 4 times
      greater than the experimentally measured value of 22 kJ/mol. In contrast, the DFT
      activation barrier for reaction at a deprotonated hydroxyl site on a tertiary
      carbon atom (triple bond C-O(-)) of 24 kJ/mol was in close agreement with the
      experimental value. Both experiments and quantum mechanical simulations support a
      TCE reduction mechanism that involves chemically adsorbed intermediates.

PMID- 19174915
TI  - Persulfate persistence under thermal activation conditions.
AB  - Contaminant destruction with in situ chemical oxidation (ISCO) using persulfate
      (peroxydisulfate, S2O8(2-)) can be enhanced by activation, which increases the
      rate of persulfate decomposition to sulfate radicals (SO4*-). This step initiates
      a chain of radical reactions involving species (including SO4*- and OH*) that
      oxidize contaminants more rapidly than persulfate does directly. Among current
      activation methods, thermal activation is the least well studied. Combining new
      data for environmentally relevant conditions with previously published data, we
      have computed three sets of Arrhenius parameters (In A and Eact) that describe
      the rate of persulfate decomposition in homogeneous solutions over a wide range
      of temperature and pH. The addition of soil increases the decomposition rate of
      persulfate due to reactions with organic matter and possibly mineral surfaces,
      but the kinetics are still pseudo-first-order in persulfate and conform to the
      Arrhenius model. A series of respike experiments with soil at 70 degrees C
      demonstrate that once the oxidant demand is met, reaction rates return to values
      near those observed in the homogeneous solution case. However, even after the
      oxidant demand is met, the relatively short lifetime of the persulfate at
      elevated temperatures (e.g., >50 degrees C) will limit the delivery time over
      which persulfate can be effective.

PMID- 19174916
TI  - Stabilization/solidification of radioactive salt waste by using xSiO2-yAl2O3
      zP2O5 (SAP) material at molten salt state.
AB  - The molten salt waste from the pyroprocess is one of the problematic wastes to
      directly apply a conventional process such as vitrification or ceramization. This
      study suggested a novel method using a reactive material for metal chlorides at a
      molten temperature of salt waste, and then converting them into manageable
      product at a high temperature. The inorganic composite, SAP (SiO2-Al2O3-P2O5),
      synthesized by a conventional sol-gel process has three or four distinctive
      domains that are bonded sequentially, Si-O-Si-O-A-O-P-O-P. The P-rich phase in
      the SAP composite is unstable for producing a series of reactive sites when in
      contact with a molten LiCl salt. After the reaction, metal aluminosilicate, metal
      aluminophosphate, metal phosphates and gaseous chlorines are generated. From this
      process, the volatile salt waste is stabilized and it is possible to apply a high
      temperature process. The reaction products were fabricated successfully by using
      a borosilicate glass with an arbitrary composition as a chemical binder. There
      was a low possibility for the valorization of radionuclides up to 1200 degrees C,
      based on the result of the thermo gravimetric analysis. The Cs and Sr leach rates
      by the PCT-A method were about 1 x 10(-3) g/(m2 day). For the final disposal of
      the problematic salt waste, this approach suggested the design concept of an
      effective stabilizer for metal chlorides and revealed the chemical route to the
      fabrication of monolithic wasteform by using a composite as an example. Using
      this method, we could obtain a higher disposal efficiency and lower waste volume,
      compared with the present immobilization methods.

PMID- 19174917
TI  - Efficiency of Artemia cysts removal as a model invasive spore using a continuous
      microwave system with heat recovery.
AB  - A continuous microwave system to treat ballast water inoculated with Artemia
      salina cysts as a model invasive spore was tested for its efficacy in
      inactivating the cysts present. The system was tested at two different flow rates
      (1 and 2 L x min(-1)) and two different power levels (2.5 and 4.5 kW).
      Temperature profiles indicate that the system could deliver heating loads in
      excess of 100 degrees C in a uniform and near-instantaneous manner when using a
      heat recovery system. Except for a power and flow rate combination of 2.5 kW and
      2 L x min(-1), complete inactivation of the cysts was observed at all
      combinations at holding times below 100 s. The microwave treatment was better or
      equal to the control treatment in inactivating the cysts. Use of heat exchangers
      increased the power conversion efficiency and the overall efficiency of the
      treatment system. Cost economics analysis indicates that in the present form of
      development microwave treatment costs are higher than the existing ballast water
      treatment methods. Overall, tests results indicated that microwave treatment of
      ballast water is a promising method that can be used in conjunction with other
      methods to form an efficient treatment system that can prevent introduction of
      potentially invasive spore forming species in non-native waters.

PMID- 19174918
TI  - Improved passive treatment of high Zn and Mn concentrations using caustic
      magnesia (MgO): particle size effects.
AB  - High concentrations of divalent metals such as Zn, Mn, Cu, Pb, Ni, Cd, Co, etc.
      are not removed satisfactorily in conventional (calcite- or organic matter-based)
      passive treatment systems. Caustic magnesia ("MgO") has been used successfully as
      an alternative alkaline material to remove these metals almost completely from
      water, but columns with coarse-grained MgO lost reactivity or permeability due to
      the accumulation of precipitates when only a small portion of the reagent had
      been spent. In the present study, MgO was mixed with wood chips to overcome these
      problems. Two columns with different MgO grain sizes were used to treat Zn- and
      Mn-rich water during one year. Performance was compared by measuring depth
      profiles of chemical parameters and hydraulic conductivity. The column containing
      25% (v/v) of MgO with median particle size of about 3 mm displayed low reactivity
      and poor metal retention. In contrast, the column containing only 12.5% (v/v) of
      MgO with median particle size of 0.15 mm depleted Zn and Mn below detection limit
      throughout the study and had a good hydraulic performance. 95% of the applied MgO
      was consumed in the zone where Zn and Mn accumulated. The fine alkaline grains
      can dissolve almost completely before the growing layer of precipitates
      passivates them, whereas clogging is prevented by the large pores of the coarse
      inert matrix (wood chips). A reactive transport model corroborated the hypotheses
      that Zn(II) was removed due to its low solubility at pH near 10 achieved by MgO
      dissolution, whereas Mn(II) was removed due to rapid oxidation to Mn(III) at this
      pH and subsequent precipitation. The model also confirmed that the small size and
      large specific surface area of the MgO particles are the key factor to achieve a
      sufficiently fast dissolution.

PMID- 19174920
TI  - A matter of potential concern: natural organic matter alters the electrical
      properties of fish gills.
AB  - Natural organic matter (NOM) is an important constituent of aquatic environments;
      however, its influence on aquatic biota remains poorly studied. In the current
      study, NOM was isolated from nine different sites in southern Ontario, Canada, by
      the on-site treatment of water by reverse osmosis, followed by cation exchange.
      NOM from each site was reconstituted to 10 mg of C/L and pH 7.0 and exposed to
      either adult rainbow trout implanted with indwelling catheters or to in vitro
      primary cultures of the gill epithelium grown on semipermeable membranes. In both
      the in vivo and in vitro preparations, NOM was found to hyperpolarize
      transepithelial potential (TEP), with the magnitude of this change correlating
      extremely well to the absorptivity of the NOM at 340 nm, which is an index of its
      aromaticity. Gill hyperpolarization appeared to be independent of Ca2+
      complexation by the NOM in all but two samples tested. We argue that NOM has
      direct actions on the ionic transport and/or permeability properties of fish
      gills. While NOM effects on the bioavailability of contaminants are well-known,
      NOM actions on such fundamental physiological properties of the gills have
      previously been overlooked. These may be of comparable or greater magnitude than
      commonly reported for other water-quality variables (e.g., hardness, pH,
      salinity) and therefore of critical importance in ecological understanding and
      risk assessment.

PMID- 19174919
TI  - Mercury emissions during cofiring of sub-bituminous coal and biomass (chicken
      waste, wood, coffee residue, and tobacco stalk) in a laboratory-scale fluidized
      bed combustor.
AB  - Four types of biomass (chicken waste, wood pellets, coffee residue, and tobacco
      stalks) were cofired at 30 wt % with a U.S. sub-bituminous coal (Powder River
      Basin Coal) in a laboratory-scale fluidized bed combustor. A cyclone, followed by
      a quartz filter, was used for fly ash removal during tests. The temperatures of
      the cyclone and filter were controlled at 250 and 150 degrees C, respectively.
      Mercury speciation and emissions during cofiring were investigated using a
      semicontinuous mercury monitor, which was certified using ASTM standard Ontario
      Hydra Method. Test results indicated mercury emissions were strongly correlative
      to the gaseous chlorine concentrations, but not necessarily correlative to the
      chlorine contents in cofiring fuels. Mercury emissions could be reduced by 35%
      during firing of sub-bituminous coal using only a quartz filter. Cofiring high
      chlorine fuel, such as chicken waste (Cl = 22340 wppm), could largely reduce
      mercury emissions by over 80%. When low-chlorine biomass, such as wood pellets
      (Cl = 132 wppm) and coffee residue (Cl = 134 wppm), is cofired, mercury emissions
      could only be reduced by about 50%. Cofiring tobacco stalks with higher chlorine
      content (Cl = 4237 wppm) did not significantly reduce mercury emissions. This was
      also true when limestone was added while cofiring coal and chicken waste because
      the gaseous chlorine was reduced in the freeboard of the fluidized bed combustor,
      where the temperature was generally below 650 degrees C without addition of the
      secondary air. Gaseous speciated mercury in flue gas after a quartz filter
      indicated the occurrence of about 50% of total gaseous mercury to be the
      elemental mercury for cofiring chicken waste, but occurrence of above 90% of the
      elemental mercury for all other cases. Both the higher content of alkali metal
      oxides or alkali earth metal oxides in tested biomass and the occurrence of
      temperatures lower than 650 degrees C in the upper part of the fluidized bed
      combustor seemed to be responsible for the reduction of gaseous chlorine and,
      consequently, limited mercury emissions reduction during cofiring. This study
      identified the important impacts of temperature profile and oxides of alkali
      metal (alkali earth metal) on mercury emissions during cofiring in the fluidized
      bed combustor.

PMID- 19174921
TI  - Functional analysis of avian metallothionein isoforms: an ecotoxicological
      approach for assessing potential tolerability to element exposure.
AB  - To assess the inducibility of avian metallothionein (MT) genes and potential
      tolerability of their protiens to element exposure, we investigated the
      transcriptional inducibilities of cormorant (Phalacrocorax carbo) and mallard
      (Anas platyrhynchos) MT genes in CV-1 cells by elements and detoxification
      potencies of their in vitro synthesized MT proteins. About 1.3 kb of 5'-upstream
      regions were sequenced for cormorant MT1 and 2 genes, where two metal-responsive
      elements were identified. Both cormorant MT promoters were dose dependently
      activated by Cd, Zn, Cu, and CH3Hg, whereas no transactivation was detected by
      Pb, TI, Ag, inorganic Hg, Cr(VI), Cr(III), As(V), As(III), Ni, Co, Rb, and Bi,
      suggesting a shared transactivational mechanism of both MTs for specific
      elements. These findings support our previous results, where Cu and Zn
      concentrations were shown to be positively correlated with hepatic MT1/2 mRNA
      levels in wild cormorants. Comparison of EC50 and LOEL (lowest observed effect
      level) for each element revealed that Cd was the most potent inducer of MT1/2
      promoters, followed by CH3Hg, Zn, and Cu. Since LOELs of CH3Hg for both MT
      promoters were higher than the hepatic levels in wild cormorants, hepatic CH3Hg
      concentration may not be high enough to induce MT mRNA in the wild population.
      Although LOELs of Cd were much lower than the hepatic concentrations detected in
      wild cormorants, no significant correlation was observed between hepatic Cd
      levels and MT mRNAs. This may be due to the masking effect of multiple elements,
      probably by Zn and/or Cu that were highly accumulated in wild cormorants.
      Cotreatment of Cd with Zn supported a possible suppression of Cd-induced MT
      expression by Zn in wild cormorants. MT1 and 2 proteins of cormorant and mallard
      endowed Escherichia coli with significantly higher growth rate than control to Cd
      exposure (500-1000 microM), implying that avian MTs could be involved in the
      detoxification of intracellular Cd. This study provides the first evidence on the
      inducibility of avian MT isoforms by specific elements and functional
      significance of each avian MT isoform in detoxifying intracellular heavy metals.
      Our in vitro approaches demonstrate their validity in predicting the response of
      MTs to element exposure in a wild avian population.

PMID- 19174922
TI  - Fractionation and bioaccumulation of perfluorooctane sulfonate (PFOS) isomers in
      a Lake Ontario food web.
AB  - The environmental ubiquity of perfluorooctane sulfonate (PFOS) is well-known.
      However, little is known about the environmental fate of individual PFOS isomers.
      In this study, we investigated the fractionation and the bioaccumulation of PFOS
      isomers in water, sediment and biota collected from Lake Ontario. A total of six
      isomers, three perfluoro-monomethyl-substituted compounds, and three perfluoro
      dimethyl isomers in addition to the linear PFOS (L-PFOS) were detected in water,
      sediment and biota. L-PFOS represented a much higher proportion of total PFOS
      (sum of linear and branched) in all organisms (>88%) compared to its proportion
      in technical PFOS (77%). The predominance of L-PFOS suggests a reduced uptake of
      branched isomers, a more rapid elimination of the branched isomers and/or a
      selective retention of the L-PFOS. The PFOS isomer profile found in biota was
      very similar to sediment, even for pelagic organisms such as zooplankton,
      suggesting greater partitioning of L-PFOS to biota and to sediment. The
      bioaccumulation factor (BAF) for L-PFOS between lake trout (whole fish) and water
      was estimated to be 3.4 x 10(4) L/kg compared with 2.9 x 10(3) L/kg for the
      monomethyl-substituted group (MM-PFOS). The remarkable difference between L-PFOS
      and branched isomer BAFs is due to an enrichment of branched isomers in water.
      The trophic magnification factor of L-PFOS (4.6 +/- 1.0) was greater than MM-PFOS
      isomers (1.3 +/- 0.17 to 2.6 +/- 0.51), whereas dimethyl-PFOS showed no
      biomagnification. The results illustrate the important influence of molecular
      structure on the bioaccumulation of perfluoroalkyl sulfonates.

PMID- 19174924
TI  - Quantitative lines of evidence for screening-level diagnostic assessment of
      regional fish community impacts: a comparison of spatial database evaluation
      methods.
AB  - Determination of local ecological impacts and stressor identification in aquatic
      ecosystems is increasingly needed and required for designing effective watershed
      management plans in various jurisdictions. Spatial database evaluation methods
      applied to available environmental data resources can provide screening-level,
      geographically based stressor identification hypotheses. Cross-comparison of the
      output of independent methods is a critical step to address common concerns with
      the interpretation of output, identify strengths and weaknesses, and reduce
      uncertainty. Two current approaches were compared in this study: (1) the "Effect
      and Probable Cause" (EPC) method and (2) a GIS "Weights-of-Evidence/Weighted
      Logistic Regression" (WOE/WLR) method. The methods were applied to the same Ohio
      (U.S.) spatial data resources to link impacts on local fish assemblages with
      various natural and anthropogenic stressors. The methods generally yielded
      significantly similar results in the identification of stressors and their
      relative influence. However, key differences were also observed between the
      methods which reflected the distinctive objectives and sensitivities of each. The
      findings show that scientific interpretation of analysis output requires an
      understanding of method characteristics, and suggests the potential value of
      utilizing multiple methods as quantitative lines of evidence in screening-level
      regional diagnostic assessment.

PMID- 19174923
TI  - Transcriptional biomarkers and mechanisms of copper-induced olfactory injury in
      zebrafish.
AB  - Metals such as copper disrupt olfactory function in fish. Unfortunately, little
      is understood of the molecular consequences of copper olfactory impairment, thus
      hindering the development of relevant diagnostic tools of olfactory injury. To
      address this critical data gap, we analyzed gene expression within olfactory
      tissues of adult zebrafish exposed to CuCl2 (6, 16, 40 ppb) for 24 h.
      Transcriptional markers of copper impairment within the entire olfactory system
      were identified and specific genes of interest (e.g., S100a, parvalbumin 8,
      olfactory marker protein, and calbindin 2-like protein) were confirmed with
      quantitative real-time PCR. In addition, we performed gene set analysis (GSA)
      using both a priori and custom pathways of gene sets specifically targeting the
      olfactory signal transduction (OST) pathway. These analyses revealed down
      regulated gene sets related to calcium channels and ion transport, g-proteins,
      and olfactory receptors. Collectively, these data demonstrate that copper causes
      a depression of transcription of key genes within the OST pathway and elsewhere
      within olfactory tissues, likely resulting in an olfactory system less responsive
      to odorants. Further, these data provide a mechanistic explanation in support of
      earlier studies of functional olfactory impairment in fish following copper
      exposure.

PMID- 19174925
TI  - Creatinine adjustment of spot urine samples and 24 h excretion of iodine,
      selenium, perchlorate, and thiocyanate.
AB  - Creatinine (CR) adjustment is widely used for the estimation of urinary 24 h
      excretion from spot urine samples. We have compared CR-adjusted values for
      urinary iodine, selenium, perchlorate, and thiocyanate to measured 24 h
      excretion. The urine samples were collected from a cohort of 14 breastfeeding
      mothers with both spot samples and 24 h collection, 52 24 h and spot sample pairs
      where the 24 h CR value fell within the "normal" adult female CR excretion range
      of 0.6-1.6 g/day were considered for this analysis. In addition, a nonlactating
      female and a male subject provided all micturitions for 1 and 5 days,
      respectively. Creatinine was analyzed with a Jaffe reaction-based automated
      analyzer. Iodine and selenium were determined with induction coupled plasma-mass
      spectrometry (ICP-MS). Perchlorate and thiocyanate were measured with ion
      chromatography (IC)-isotope dilution tandem mass spectrometry (MS/MS). Creatinine
      adjusted values were poor substitutes of the actual 24 h excretion values
      (average deviation +/-69, 78, 105, and 104% for iodine, selenium, perchlorate,
      and thiocyanate, respectively.). Over a 5 day period, the 24 h iodine excretion
      predicted based on creatinine adjustment of spot samples for the same individual
      deviated between -83.5 to +101% from the actual measured value, the minimum
      absolute error being 2.5%. Creatinine adjustment for estimation of 24 h excretion
      from spot samples was not effective for iodine, selenium, perchlorate, or
      thiocyanate.

PMID- 19174926
TI  - Quantum dot weathering results in microbial toxicity.
AB  - Quantum dots (QDs) are increasingly being used for electronics, solar energy
      generation, and medical imaging applications. Most QDs consist of a heavy metal
      core/shell coated with amphiphilic organics that stabilize the nanoparticles and
      allow conjugation with biological molecules. In this study, QDs were evaluated
      for their effects on bacterial pure cultures, which serve as models of cell
      toxicity and indicators of potential impact to ecosystem health. QDs with intact
      surface coatings decreased growth rates of Gram positive Bacillus subtilis and
      Gram negative Escherichia coli but were not bactericidal. In contrast, weathering
      of various types of QDs under acidic (pH < or = 4) or alkaline (pH > or = 10)
      conditions significantly increased bactericidal activity due to the rapid (< 1
      min) release of cadmium and selenite ions following QD destabilization upon loss
      of the organic coating. Toxicity was mitigated by humic acids, proteins, and
      other organic ligands that reduced metal bioavailability. The best available
      science, which is limited, suggests that QDs are potentially safe materials when
      used in their intended applications at near-neutral pH. These results forewarn us
      that even moderately acidic or alkaline conditions could lead to significant and
      localized organism effects due to toxic exposure to dissolved heavy metals. Thus,
      biocompatibility and ecotoxicity tests for QDs should consider in vivo and/or in
      situ transformations to fully characterize the potential risks to environmental
      health.

PMID- 19174927
TI  - Influence of humic acid on bioavailability and toxicity of benzo[k]fluoranthene
      to Japanese medaka.
AB  - Japanese medakas (Oryzias latipes) and triolein-embedded cellulose acetate
      membranes (TECAMs) were exposed simultaneously to benzo[k]fluoranthene (BkF) in
      the static exposure system containing different concentrations of humic acid
      (HA). The concentration-response relationships of induced hepatic 7-ethoxysorufin
      o-deethylase (EROD) activity were established in regard to the nominal water
      concentration of BkF and the free concentration estimated using TECAM, as well as
      the body residues, respectively. In general, bioaccumulation of BkF and EROD
      activity in medaka were reduced with an increase of HA concentration in the
      exposure medium. The concentration-response relationships varied with HA
      concentration when expressed in nominal concentration. However, these
      relationships overlapped completely and partially when expressed in body BkF
      residue and in free BkF concentration estimated by TECAM, respectively. HA
      treatments were slightly beyond the 0.95 confidence band of HA-free control
      thereby indicating the participation of BkF-HA complex to the bioavailability and
      toxicity. On the basis of the bioavailability model, it was estimated that
      approximately 17-22% and 13-18% of BkF-HA complex contributed to the
      bioaccumulation and/or to the induced toxic effect, correspondingly.

PMID- 19174928
TI  - Is perchlorate metabolized or re-translocated within lettuce leaves? A stable
      isotope approach.
AB  - Perchlorate is an environmental contaminant that is found in drinking water and a
      variety of foodstuffs, but many questions regarding its uptake, transport, and
      persistence in higher plants remain unanswered. In a series of hydroponic
      experiments, a stable-isotope tracer of perchlorate (95% 37ClO4(-)) was utilized
      to determine the extent of in vivo metabolism and of phloem re-translocation of
      perchlorate at low (i.e., nmol/kg of fresh weight (FW)) concentrations in
      lettuce. Chlorate and chlorite metabolites were not detected in lettuce leaves at
      detection limits of 13.1 and 291 nmol/kg FW, respectively, and chloride isotopic
      signatures were not substantially different from natural chloride. Perchlorate
      exhibited no significant movement from older leaves into new leaves, nor to
      roots. Stable isotopes proved useful in assessing perchlorate metabolism and re
      translocation within lettuce at nmol/kg levels. The absence of any metabolism or
      re-translocation indicates that perchlorate is relatively persistent within leafy
      produce, and that the primary mode of transport of perchlorate is through the
      xylem of higher plants.

PMID- 19174929
TI  - Bioaccessibility of platinum group elements in automotive catalytic converter
      particulates.
AB  - The bioaccessibilities of the platinum group elements (PGE): Rh, Pd, and Pt; and
      the catalyzator poison, Pb, have been determined in particles derived from milled
      automotive catalytic converters using a physiologically based extraction test
      (PBET) that simulates, sequentially, the chemical conditions encountered in the
      human stomach and intestine. PGE accessibility, relative to total metal
      concentration, was generally less than a few percent, but increased in the
      stomach with decreasing pH (from 4 to 1) and/or increasing chloride
      concentration, and with decreasing particle concentration. In most cases,
      bioaccessibility increased from the acidic stomach to the neutral, carbonate-rich
      intestine. Bioaccessibility of Pb displayed similar pH and particle concentration
      dependencies to PGE in the stomach, but this metal exhibited significantly
      greater mobilization (up to 80%) overall and a reduction in accessibility from
      the stomach to intestine. Reaction kinetics of PGE dissolution in the stomach at
      pH 2.5 were modeled using a combined surface reaction-diffusion controlled
      mechanism with rate constants of 0.068, 0.031, and 0.015 (microg L(-1))(-1) h(-1)
      for Rh, Pd, and Pt, respectively. For Pb, however, mobilization proceeded via a
      different mechanism whose time-dependence was fitted with an empirical,
      logarithmic equation. Overall, PGE bioaccessibility appeared to be controlled by
      dissolution rates of metallic nanoparticles in the stomach, and solubility and
      kinetic constraints on inorganic species (chlorides, hydroxychlorides, and
      carbanatochlorides) and undefined organic complexes formed in the simulated
      gastrointestinal tract. Further studies are required to elucidate any effects
      engendered by the long-term oral exposure of small quantities of these species.

PMID- 19174930
TI  - Comment on "Bioconcentration factor hydrophobicity cutoff: an artificial
      phenomenon reconstructed".

PMID- 19174931
TI  - Comment on "Alternate and new brominated flame retardants detected in U.S. house
      dust".

PMID- 19174932
TI  - [The natural course of non-functioning pituitary adenomas].
AB  - 3 patients presented with non-functioning pituitary adenomas: a 50-year-old woman
      who had an adenoma that had not increased in size for 3 years; a 68-year-old man
      with an adenoma that was undiagnosed for 5 years and led to pituitary
      insufficiency and bitemporal hemianopsia; and a 64-year-old woman, who had
      refused therapy and follow-up after diagnosis of the adenoma 20 years earlier.
      She was admitted with a hydrocephalus, pituitary insufficiency, and severe visual
      loss. The clinical symptoms of pituitary adenomas are caused by the mass effects
      of the tumour and may vary considerably between patients. Transsphenoidal surgery
      is indicated in cases of suprasellar extension with compression or impending
      compressing of the optic chiasm. A 'wait-and-see' approach can be used for
      patients with smaller tumours and no visual field defects. The natural course of
      these adenomas is such that lifelong follow-up is necessary. Postoperative
      radiotherapy can be effective in reducing recurrence rates without negative
      effects on quality of life.

PMID- 19174933
TI  - [The practice guideline 'Urinary incontinence' (first revision) from the Dutch
      College of General Practitioners; a response from the perspective of urology].
AB  - The revised practice guideline 'Urinary incontinence' of the Dutch College of
      General Practitioners contains some important changes. Urodynamic investigation
      is not mandatory for differentiating between types of incontinence in the general
      practice setting. Physical examination including a valsalva leak point test is
      considered important. From a urological point ofview it remains to be seen
      whether the history-taking and the physical examination described in the revised
      guideline will be enough to accurately differentiate between the possible
      incontinence types. The practice guideline underlines a role for the general
      practitioner in teaching bladder training or pelvic floor exercises. The benefits
      of this compared to exercises taught by specialized physiotherapists will have to
      be determined. Another new feature is that antimuscarinic drugs are mentioned as
      proper treatment for people suffering from overactive bladder complaints. The
      practice guideline advises referral of male incontinence patients only if the
      incontinence is not related to prostate surgery. However, patients with
      postoperative incontinence should also be referred as there are good diagnostic
      and therapeutic options available.

PMID- 19174934
TI  - ['State of the nation's healthcare 2008' annual report: technology is useful, but
      training comes first].
AB  - The Netherlands Health Care Inspectorate's annual report on the state of the
      nation's healthcare in 2008 is dedicated to the use of medical technology. The
      subtitle of the report is 'Risks of medical technology underestimated'. Lack of
      education and training expose patients to an unacceptable risk of injury within
      both the care and the cure setting. The Inspectorate urgently recommends applying
      a certification system to physicians to guarantee safe and appropriate use of
      devices and equipment. The administration of an institution has the primary
      responsibility for the visible implementation of risk and safety management.
      Also, the medical professional must become familiar with the principles of
      engineering and be trained in applying a systematic approach to safety and
      reliability within medical technology. This annual report provides
      recommendations on how to incorporate biomedical engineering into medical
      education.

PMID- 19174935
TI  - [Therapy resistance of gastro-oesophageal reflux symptoms: acid reflux, non-acid
      reflux or no reflux].
AB  - The introduction of proton pump inhibitors (PPIs) was a huge step forward in the
      treatment of gastric acid-related disorders such as reflux disease and gastric
      ulcers. Despite the strong effectiveness of PPIs, in a small number of patients
      reflux symptoms are not adequately relieved by these drugs. The amount of acid
      inhibition that can be achieved using a PPI depends on a number of different
      factors, such as Helicobacter pylori infection, genetic variation in metabolizing
      enzymes, and lack of compliance. Nocturnal gastric acid breakthrough does not
      appear to be important in the pathogenesis of therapy-resistant reflux symptoms.
      Not all reflux from the stomach into the oesophagus appears to be acidic.
      Episodes of non-acid reflux may also elicit typical reflux symptoms. This can be
      established by impedance measurements of the oesophagus. However, most patients
      whose symptoms do not respond satisfactorily to PPI therapy appear not to have
      reflux disease but instead be suffering from other conditions such as functional
      dyspepsia, aerophagy or rumination. Careful history-taking is pivotal in patients
      with reflux symptoms and should always precede additional investigations such as
      upper endoscopy and if necessary 24-hour reflux monitoring.

PMID- 19174936
TI  - [Therapy-resistant gastro-oesophageal reflux disease: endoluminal treatment not
      yet sufficiently compared with the gold standard, the laparoscopic Nissen
      fundoplication].
AB  - Gastro-oesophageal reflux disease (GORD) is treated primarily with proton pump
      inhibitors. More invasive treatment is only indicated for patients with
      persistent symptoms or when complications occur. Anti-reflux surgery is
      successful in 85-90% of patients in terms of symptom control, healing of
      oesophagitis and normalization of oesophageal stomach-acid exposure. Laparoscopic
      Nissen fundoplication is the standard surgical procedure and favourable results
      persist for at least 5 years. Endoluminal treatment for GORD is a new development
      for which no long-term results are known and which can probably only be
      implemented in some of the patients with disease refractory to therapy. The
      effect of the new endoluminal treatments will have to be evaluated in randomised
      trials and to be compared with the medical gold standard of treatment, proton
      pump inhibitors, and with the surgical gold standard, laparoscopic Nissen
      fundoplication.

PMID- 19174938
TI  - [Diagnostic image (397). A neonate with an abnormal position of the right arm].
AB  - A term girl was born by breech delivery. At physical examination the right elbow
      joint was swollen and extremely flexible, due to a luxation of the radius head.

PMID- 19174937
TI  - [Summary of the practice guideline 'Urinary incontinence' (first revision) from
      the Dutch College of General Practitioners].
AB  - Two years after revision of the practice guideline 'Urinary incontinence' from
      the Dutch College of General Practitioners, it is time for a summary of the most
      important changes. The use of a bladder diary is recommended. In primary care, a
      stress test does not provide more information than history taking. Routine
      urodynamic testing is not indicated for patients presenting to their general
      practitioner with urinary incontinence. Treatment of stress, urge and mixed
      incontinence can usually be commenced in primary care; pelvic floor exercises and
      bladder training are preferred. If bladder training is not effective for urge
      incontinence, anticholinergic drugs should be considered. The use of oral and
      vaginal oestrogens and flavoxate is no longer recommended.

PMID- 19174940
TI  - [A woman with right-sided lower abdominal pain due to intussusception of the
      appendix].
AB  - A 38-year-old woman presented with mild abdominal pain in the right inferior
      quadrant. Ultrasonography and CT scan suggested intussusception in the ileocoecal
      region. At exploratory laparotomy an invagination ofthe appendix through the
      appendicial base into the coecum was found. Pathological findings were: presence
      of peri-appendicitis and foci ofendometriosis in the peri-appendiceal fatty and
      connective tissue. Intussusception of the appendix is mostly found in children,
      particularly in boys.

PMID- 19174939
TI  - [Transsphenoidal resection of pituitary adenomas: long-term results from the
      Leiden University Medical Center].
AB  - OBJECTIVE: To evaluate the long-term outcome of transsphenoidal resection of
      pituitary adenomas at the Leiden University Medical Center (LUMC), The
      Netherlands. DESIGN: Retrospective, descriptive. METHOD: 416 consecutive patients
      undergoing surgery for pituitary adenoma at the LUMC between 1978 and 2004 were
      included; 174 patients with non-functioning macroadenomas (NFMA), 164 patients
      with acromegaly and 78 patients with Cushing's disease. RESULTS: Biochemical
      remission was achieved in 66% of patients with acromegaly, and 72% of patients
      with Cushing's disease; incidence of pituitary failure was low in these patients
      (5% and 18% respectively). In 82% of the patients with NFMA visual function
      improved whereas the percentage with any degree of pituitary failure increased
      from 85% (preoperatively) to 95% (postoperatively). During follow-up of 10-15
      years, the recurrence rate for acromegaly and Cushing's disease was 9% and for
      NFMA it was 15%. CONCLUSION: Transsphenoidal resection is an effective treatment
      in most, but not all, patients with pituitary adenomas. The surgical results at
      the LUMC are comparable with those obtained in important international centres.
      All patients cured by surgery need lifelong follow-up, because of the real risk
      of recurrent disease.

PMID- 19174941
TI  - [Hyponatraemia as a clinical manifestation of hypopituitarism caused by
      neurosarcoidosis].
AB  - Severe hyponatraemia was observed in a 35-year-old man with progressive malaise;
      this was caused by hypopituitarism and secondary hypocortisolism as a result
      ofneurosarcoidosis. Sarcoidosis is a multisystem granulomatous disorder of
      unknown aetiology which can develop in any of the body's organs or tissues. The
      central nervous system is affected in only 5-15% of patients with sarcoidosis.
      Neurosarcoidosis is a rare disorder with clinical heterogeneity. Extensive
      diagnostic procedures, including MRI of the cerebrum and histological
      investigation, and structural outpatient follow-up are mandatory in patients in
      whom neurosarcoidosis is suspected. Treatment consists mainly of high-dose
      corticosteroids, which usually have to be taken long-term. Clinical course and
      prognosis are variable, and depend on the accompanying symptoms.

PMID- 19174942
TI  - [Fish fatty acids and cardiovascular diseases--an update].

PMID- 19174943
TI  - [May modern surgery be cheap?].

PMID- 19174944
TI  - [Thoracoscopic thymectomy--initial experience].
AB  - Video-assisted thymectomy and its variations is not generally accepted approach
      in surgical treatment of myasthenia gravis yet. Authors present their initial
      experience with videothoracoscopic technique in surgery for thymic cysts and
      myasthenia gravis. Authors prefer left thoracoscopic approach which allows good
      view to the thymus in mediastinum and neck. Recent studies confirm generally
      known advantages of miniinvasive surgery and show no differences between open and
      thoracoscopic thymectomy in terms of treatment outcome of myasthenia gravis.
      Nevertheless, prospective randomized study comparing open and thoracoscopic
      thymectomy in myasthenia gravis is not known.

PMID- 19174945
TI  - [Cystic neoplasms of the pancreas].
AB  - INTRODUCTION: Neoplastic changes represent an important part of cystic deposits
      in pancreas. It is morphologically non-homogenous group of neoplasms with
      different occurrence depending on sex and age, different localization and
      different biologic properties. The aim of the paper is to remind current
      knowledge of this topic and confront it with our own experience. MATERIAL AND
      METHODS: Together 13 patients with histologically proved cystic neoplasm of
      pancreas underwent surgery during the period of ten years from 1997 to 2007. They
      represent 6% of all patients operated for pancreatic tumor (213 patients). Women
      (9 patients) represented more than two thirds of all operated patients and
      deposits were more often localized in the head of pancreas (8). RESULTS: The most
      frequent operation was partial duodenopancreatectomy (7) and most frequently
      cystadenocarcinoma was identified histologically (5 times). Median survival of
      these patients is 54 months. Left sided resection, done in 5 cases, identified
      benign tumor in all patients; no recurrence was found in 2 years follow-up.
      CONCLUSION: Cystic neoplasms localized in the pancreatic head are more frequent
      in men than in women and predominantly malignant, on the contrary localization in
      the tail of pancreas is particularly in younger women linked with benign tumor.
      Prognosis after resection is markedly better in malignant processes even in
      comparison with ductal carcinoma.

PMID- 19174946
TI  - [Acute abdomen following duodenal biopsy].
AB  - One possibility of verifying malabsorbtion is by doing a biopsy of the duodenal
      mucosa for a histochemical examination. The authors present a complicated biopsy
      with a duodenal intramural haematoma, with caused signs of an ileus condition and
      of haemoperitoneum.

PMID- 19174947
TI  - [Radiofrequency ablation (RFA) of pancreatic tumors].
AB  - The authors refer about their first experience with radiofrequency ablation of
      locally advanced pancreatic tumors. They put forward the prospective study of
      five patients (four with ductal adenocarcinoma of the head and one with malignant
      neuroendocrine tumor of pancreatic body), who either because of local advanced
      disease or performance status, were not able to undergo radical curative surgery.
      All patients underwent peroperative radiofrequency ablation of pancreatic tumors.
      In the case of pancreatic head localization, posterior retrocolic gastro
      enterostomy and hepatico-jejunostomy to Y Roux jejunal loop were performed. There
      was no perioperative mortality. In one case duodenal leak apeared in the fourth
      postoperative day. This was healed conservatively by drainage. At one patient the
      subfascial absces developed. This was solved by drainage reoperation at the
      fourteenth postoperative day. After consolidation, all patients were released to
      home care. CONCLUSION: According to our early experience, radiofrequency ablation
      of inoperable pancreatic tumors is relatively save cytoreductive procedure.

PMID- 19174948
TI  - [Interdisciplinary European guidelines on surgery for severe obesity].

PMID- 19174949
TI  - [Closed femoral fracture complicated by blunt injury and posttraumatic occlusion
      of the superficial femoral artery--a case review].
AB  - The diagnosis and the treatment of an unusual posttraumatic occlusion of a
      femoral superficial artery during skeletal traction has been described.
      Angiography of the arteries of lower extremities was done because a sharp pain,
      cold, parestesia of the foot and absent pulsies had been found. The occlusion of
      the right femoral superficial artery was seen in the place of the compression of
      the artery by a fragment of femur. The fracture of the femur was stabilized with
      Ender's rods immediately and the injured part of the artery was resected and
      replaced by a venous graft. The healing was without any complication. The
      symptoms, the diagnostic procedures and the therapy of the occlusion of the
      arteries caused by fractures of the extremities has been discussed.

PMID- 19174950
TI  - [Fractures of sternal end of the clavicle--current concept review].
AB  - Fractures of the medial end of the clavicle are still an outstanding issue with
      only minimum information available. Their diagnosis requires a special care both
      in isolated fractures of the clavicle and in polytrauma. An accurate diagnosis is
      impossible without CT scanning, preferably with a 3D reconstruction. Non
      displaced fractures are indicated for non-operative treatment. In displaced
      fractures, sustained particularly by younger or active individuals, operative
      treatment should be considered. Best suitable for fixation is a cerclage, K-wires
      are strictly contraindicated. Formulation of a more specific opinion on the
      method of treatment, long-term outcomes and complications will be possible only
      on the basis of a greater number of reported cases.

PMID- 19174951
TI  - [Six-month functional and X-ray outcomes of distal radius fractures managed using
      multidirectional locking plates].
AB  - INTRODUCTION: Distal radius fractures remain the commonest fractures in the human
      body. Developed countries have recorded increasing rates of these fracures.
      MATERIAL AND METHODS: The authors assess results of distal radius osteosynthesis
      procedures using the Aptus Radius 2.5 mm (Medartis, Schweiz) system, consisting
      of 18 types of multidirectional, locking plates, designated for osteosyntheses
      and corrective osteotomies of the distal radius. The authors evaluate six-month
      results in 66 patients operated from January to September 2007. All AO types of
      fractures were included in the study group.The mean age of the patients was 49.5
      years. RESULTS: According to X-ray, the mean healing time was 7 weeks. 6 moths
      following the procedure, the radius length was +0.4 mm (ranging from +4 mm to -4
      mm), the radial inclination was 21 degrees (ranging from 13 degrees to 29
      degrees) and the palmar tilt of the articular surface was 7 degrees (ranging from
      0 degrees to 10 degrees of the palmar tilt). The range of motion, compared to the
      other extremity, was as follows: palmar flexion 87.5%, dorsal flexion 91.5%,
      radial duction 90.5%, ulnar duction 88.2%, pronation 98.1% and supination 94.3%.
      The mean grip strength reached 85% of that of the contralateral extremity.
      DISCUSSION: Fragment-specific fixation using the Aptus radius system, provides
      enough stability to prevent secondary loss of correction. Functional and
      radiological outcomes were similar to those with other types of locking plates.
      The results obtained from this study correspond to data presented in other recent
      studies assessing multidirectional locking plates. CONCLUSION: Central, targeted
      fixation of the fracture fragments and introduction of locking screws provide
      stability, which minimizes duration of additional fixation and facilitates early
      rehabilitation. It can be used for osteosynthesis of all types of fractures
      according to AO classification and, in particular, optimizes fixation of the C.2.
      and C.3. fracture types.

PMID- 19174952
TI  - Proposal for a new categorization of aseptic processing facilities based on risk
      assessment scores.
AB  - Risk assessment of aseptic processing facilities was performed using two
      published risk assessment tools. Calculated risk scores were compared with
      experimental test results, including environmental monitoring and media fill run
      results, in three different types of facilities. The two risk assessment tools
      used gave a generally similar outcome. However, depending on the tool used,
      variations were observed in the relative scores between the facilities. For the
      facility yielding the lowest risk scores, the corresponding experimental test
      results showed no contamination, indicating that these ordinal testing methods
      are insufficient to evaluate this kind of facility. A conventional facility
      having acceptable aseptic processing lines gave relatively high risk scores. The
      facility showing a rather high risk score demonstrated the usefulness of
      conventional microbiological test methods. Considering the significant gaps
      observed in calculated risk scores and in the ordinal microbiological test
      results between advanced and conventional facilities, we propose a facility
      categorization based on risk assessment. The most important risk factor in
      aseptic processing is human intervention. When human intervention is eliminated
      from the process by advanced hardware design, the aseptic processing facility can
      be classified into a new risk category that is better suited for assuring
      sterility based on a new set of criteria rather than on currently used
      microbiological analysis. To fully benefit from advanced technologies, we propose
      three risk categories for these aseptic facilities.

PMID- 19174953
TI  - Monitoring minimization of grade B environments based on risk assessment using
      three-dimensional airflow measurements and computer simulation.
AB  - A practical, risk-based monitoring approach using the combined data collected
      from actual experiments and computer simulations was developed for the
      qualification of an EU GMP Annex 1 Grade B, ISO Class 7 area. This approach can
      locate and minimize the representative number of sampling points used for
      microbial contamination risk assessment. We conducted a case study on an aseptic
      clean room, newly constructed and specifically designed for the use of a
      restricted access barrier system (RABS). Hotspots were located using three
      dimensional airflow analysis based on a previously published empirical
      measurement method, the three-dimensional airflow analysis. Local mean age of air
      (LMAA) values were calculated based on computer simulations. Comparable results
      were found using actual measurements and simulations, demonstrating the potential
      usefulness of such tools in estimating contamination risks based on the airflow
      characteristics of a clean room. Intensive microbial monitoring and particle
      monitoring at the Grade B environmental qualification stage, as well as three
      dimensional airflow analysis, were also conducted to reveal contamination
      hotspots. We found representative hotspots were located at perforated panels
      covering the air exhausts where the major piston airflows collect in the Grade B
      room, as well as at any locations within the room that were identified as having
      stagnant air. However, we also found that the floor surface air around the exit
      airway of the RABS EU GMP Annex 1 Grade A, ISO Class 5 area was always remarkably
      clean, possibly due to the immediate sweep of the piston airflow, which prevents
      dispersed human microbes from falling in a Stokes-type manner on settling plates
      placed on the floor around the Grade A exit airway. In addition, this airflow is
      expected to be clean with a significantly low LMAA. Based on these observed
      results, we propose a simplified daily monitoring program to monitor microbial
      contamination in Grade B environments. To locate hotspots we propose using a
      combination of computer simulation, actual airflow measurements, and intensive
      environmental monitoring at the qualification stage. Thereafter, instead of
      particle or microbial air monitoring, we recommend the use of microbial surface
      monitoring at the main air exhaust. These measures would be sufficient to assure
      the efficiency of the monitoring program, as well as to minimize the number of
      surface sampling points used in environments surrounding a RABS.

PMID- 19174954
TI  - In vitro permeation of carvedilol through porcine skin: effect of vehicles and
      penetration enhancers.
AB  - This investigation studied the effect of vehicles on the in vitro permeation of
      carvedilol from saturated solutions across porcine skin and selected appropriate
      penetration enhancers. Labrasol, Transcutol, polyethylene glycol 400, propylene
      glycol, ethanol, oleic acid, isopropyl myristate, and phosphate buffered saline
      (pH 7.4) containing 40% v/v polyethylene glycol 400 as control, were used as
      vehicles; limonene, carvone, camphor, menthol, Transcutol, and Labrasol at 5% w/v
      concentrations were used as penetration enhancers. Skin permeation studies were
      conducted in Franz diffusion cells using excised porcine ear skin. Solubility was
      highest (369.13 mg/mL) in Transcutol, whereas isopropyl myristate showed the
      lowest solubility (0.79 mg/mL) among all the vehicles. The flux of carvedilol
      from Transcutol, Labrasol, polyethylene glycol 400, ethanol, and oleic acid was
      10.5, 8.6, 4.2, 2.9, and 1.5 times higher, respectively, than that observed with
      control. The flux obtained using Transcutol was significantly higher (P < 0.05)
      than the flux obtained using the other vehicles. However, the flux values of
      carvedilol using isopropyl myristate (P < 0.01) and propylene glycol (P < 0.05)
      were significantly lower than that of the control. Solutions containing 5% w/v
      camphor showed maximum permeation (232.54 microg) in 24 h with a flux of 3.19
      microg/cm2/h, which was significantly different (P < 0.05) than the flux obtained
      using other permeation enhancers. The control sample showed lowest permeation
      (30.50 microg), with a flux of 0.33 microg/cm2/h. The flux of carvedilol from the
      solutions containing 5% w/v camphor, limonene, Transcutol, carvone, Labrasol, and
      menthol were 9.7, 7.6, 7.6, 6.3, 4.7, and 2.3 times higher, respectively, than
      that observed using the control. The present study suggests that Transcutol,
      Labrasol, and polyethylene glycol 400 may be used as potential vehicles and
      camphor, limonene, and Transcutol at a 5% w/v level as penetration enhancers.

PMID- 19174955
TI  - Selective drug delivery to the colon using pectin-coated pellets.
AB  - A combination of ethylcellulose and pectin, when applied as a film coat, has a
      potential value as a colon-specific delivery system. Dispersions of pectin in
      ethylcellulose were used as the film former for coating of 5-aminosalicylic acid
      (5-ASA) pellet cores. Drug release behavior was assessed, in vitro, under
      simulating conditions in term of pH and time in vivo during transit to the colon.
      Negligible drug release occurred during first 5 h, when the coated pellets were
      in the simulated gastric and small intestinal conditions. After that, rat cecal
      contents were added into the pH 6.8 medium to simulate the in vivo condition
      where there is the digestion of bacteria in the colon. Drug release depended on
      the composition of the mixed film, as well as the ratio of ethylcellulose to
      pectin. Drug release profiles seemed to conform to the mechanism involving the
      osmotically driven release and formation of channels in the film caused by
      dissolution of pectin. Channel formation was, in most cases, activated by the
      presence of rat cecal contents, showing that the pectin in the mixed film was
      subjected to enzymic breakdown. In conclusion, pectin could be used as an
      additive in ethylcellulose films to control the release of colonic delivery
      system. In addition, the mechanism of the hydrophilic drug release from pellets
      coated with ethylcellulose aqueous dispersions containing an aqueous gel-forming
      polymer (pectin) is also discussed.

PMID- 19174956
TI  - High-pressure treatment, a potential antimicrobial treatment for pharmaceutical
      preparations? A survey.
AB  - Sterilization by means of heat, irradiation and gas are methods universally used
      for the production of microbiologically safe pharmaceutical preparations, medical
      devices, and foods. However, in many cases limited chemical and physical
      stability, interaction with the sterilizing agent, and legal restrictions
      prohibit the use of these methods. About two decades ago high hydrostatic
      pressure (HHP) treatment was introduced as a commercially attractive alternative
      sterilizing method for the food industry. HHP is, under appropriate conditions,
      virucidal, bactericidal, sporicidal, and fungicidal. To achieve a sporicidal
      effect, the combined action of pressure and heat is necessary. The survival
      curves of both spores and vegetative cells often exhibit a biphasic or a sigmoid
      shape. Therefore, the development of reliable sterilization cycles requires
      detailed studies with individual products. So far the potential application of
      this relatively new technology has been studied only incidentally for
      pharmaceutical preparations. In this paper the HHP process, its mode of action,
      and its kinetics are reviewed. HHP's possible applications for pharmaceutical
      purposes are discussed.

PMID- 19174957
TI  - In vitro evaluation of porous carrier-based floating granular delivery system of
      orlistat.
AB  - The purpose of the study is to prepare and evaluate an intragastric floating
      granular delivery system of orlistat using (i) calcium silicate as porous
      carrier; and (ii) hydroxypropyl methylcellulose K4M, ethyl cellulose, and
      Carbopol 940 as matrix-forming polymers. The effect of various formulation and
      process variables on the micro-meritic properties, in vitro floating behavior,
      percent drug content, and in vitro drug release was studied. The release
      mechanism of orlistat from these granules was evaluated on the basis of various
      theoretical equations. The optimized formulation demonstrated favorable in vitro
      floating and release characteristics. The release pattern of optimized, secondary
      coated granules of orlistat in simulated gastrointestinal fluids corresponded
      best to the Peppas-Korsmeyer model and Higuchi matrix model. The results clearly
      indicated the controlled and sustained release of orlistat from its gastro
      retentive floating granular delivery system.

PMID- 19174958
TI  - Preformulative assessment of preformed complexes of gemfibrozil, with
      cyclodextrins.
AB  - The aim of this study is to carry out preformulative investigations on preformed
      inclusion complexes of the poorly water-soluble, lipid-lowering agent gemfibrozil
      and naturally occurring cyclodextrins (CDs). Phase solubility studies showed a
      linear AL- type diagram with alpha, beta, and y cyclodextrins, indicating the
      formation of inclusion complexes in a 1:1 molar ratio with all the three CDs.
      beta-CD-gemfibrozil complex having a maximum stability constant of 148.88 M(-1)
      was selected for preparation of preformed inclusion complex by kneading, co
      precipitation, co-evaporation, and freeze-drying and compared with the physical
      mixture. The kneaded product was subjected to microwave-drying, with this mode of
      drying studied as an alternative method for preparation of the complex. The
      prepared complexes were assessed by equilibrium solubility analysis and intrinsic
      dissolution rate studies. Further characterization was done by differential
      scanning calorimetry, X-ray powder diffractometry, Fourier transform infrared
      spectroscopy, and scanning electron microscopy. The freeze-dried product was
      identified as the inclusion complex having the maximum intrinsic dissolution rate
      and hence was assessed for changes in permeability characteristics. pH partition
      studies and partial in vivo permeability studies showed no changes in the
      permeability of the freeze-dried product when compared to the pure drug.

PMID- 19174959
TI  - More on Medicare and the presidential candidates.

PMID- 19174960
TI  - Is it time to sell?
AB  - Hospitals are purchasing physician practices at a rate not seen since the 1990s,
      and the action is widespread. Doctors all over the country--in practices large
      and small, successful and struggling--are jumping at the chance to leave the
      complexity, business risks, and stagnant economics of private practice for the
      perceived security of a larger organization. This article examines the trend and
      offers suggestions for physicians to determine whether or not selling is the
      right move.

PMID- 19174961
TI  - Let physicians be physicians.
AB  - On a recent visit to his physician, a friend reported that the physician spent
      95% of the visit hunched over a laptop computer, leaving it only for a quick
      listen to his heart and lungs. The remarkable thing is, in medical circles the
      story is unremarkable. Many consider it the norm now. Who thought it was a good
      idea to turn physicians into typists? Does it make sense that the most highly
      educated person in the building is doing data entry? How is patient care improved
      if the physician is hunched over a laptop computer in the exam room?

PMID- 19174962
TI  - Five-star service: the simple truth.
AB  - That happens when a consultant who teaches five-star service to healthcare
      practices becomes a patient? From the initial evaluation in a private practice,
      through surgery and rehabilitation, this article outlines the first-hand
      experience of the author and outlines the simple truth about how to stand out in
      your community as the premier provider of quality care and customer service.

PMID- 19174963
TI  - What's so different in documentation for teaching physicians?

PMID- 19174964
TI  - What's in your contract?
AB  - Crafting clear and factual contract language is a process that few practices take
      into consideration when purchasing software and hardware to run their practices.
      This article looks at many important facets that are often neglected in
      negotiating with vendors prior to purchase. In the end, what is written in the
      contract will drive the success or failure of technology implementation and
      satisfaction.

PMID- 19174965
TI  - Computer briefs: home telemedicine.

PMID- 19174966
TI  - Six Sigma and modifications to gain an efficient practice.
AB  - Practices are inefficient in many areas of processing. Industry has an approach-
      Six Sigma--that works well. However, this process in its truest approach is not
      practical to implement in a medical practice. However, the philosophy of
      continuous improvement and developing an approach in any size medical practice
      can and will result in improvements. These improve ments will allow staff to
      focus on more important issues as well as improve the bottom line and cash flow.

PMID- 19174967
TI  - Quit singing the blues.

PMID- 19174968
TI  - How to keep the practice on schedule: 30 tips for the medical practice staff.
AB  - It isn't always easy to keep a busy medical practice on schedule. However, a
      quick-thinking staff member can work wonders to avoid scheduling bottlenecks and
      realign an appointment schedule that's careening out of control. This article
      offers 30 specific strategies for the medical practice staff to help them keep
      the practice on schedule. It suggests that taking a proactive approach to
      handling problems is best and that analyzing patterns within the schedule can
      uncover problems that staff members will be able to solve once and for all. This
      article also offers the medical practice staff effective strategies for
      minimizing the number of daily interruptions and explains how anticipating the
      physician's needs can save valuable production time. Finally, this article urges
      staff members to consider how identifying and working with the physician's
      scheduling preferences can make everyone happier and enable the practice to stay
      on schedule.

PMID- 19174969
TI  - Practical strategies for implementing integrative medicine in a primary care
      setting.
AB  - Rapid growth of the holistic healthcare and natural products fields over the last
      10 years reflects strong public interest in preventive medicine and a
      dissatisfaction with mainstream allopathic approaches. Medical schools and
      hospital systems have tried to meet the public's interest by educating physicians
      and providing hospital-affiliated integrative clinics. While many primary care
      doctors have shown interest in learning about nutrition, botanical medicine,
      stress management, and other aspects of holistic care, implementation in practice
      has been challenging. In large part, this is because most holistic services are
      not covered by insurance plans. Physicians wishing to practice
      holistic/integrative medicine must develop new practice models. This article
      explores the pros and cons of the various emerging models for
      integrative/holistic healthcare.

PMID- 19174970
TI  - A retrospective of EMR implementation in one large practice.
AB  - This article is the last of a six-part series regarding the implementation of an
      electronic medical record system in a large multisite physician practice. This
      particular article is meant to provide some insight regarding two matters any
      practice delving into this project should be prepared to consider: 1) don't
      underestimate the value of utilizing as many employees as possible in the pre
      implementation planning stage; and 2) have a detailed plan for entering patient
      history information.

PMID- 19174971
TI  - It took two decades for private payor contracts to erode the bottom line: plan on
      a 2+ year comeback--here's how, Part IV.
AB  - You've negotiated new rates with your payors and think it is time to celebrate.
      But wait, there is another step in the renegotiation process that protects the
      rates and alleviates some of the confusion about administrative issues. Among the
      contractual provisions discussed in this article are timely payment, timely
      submission, retroactive eligibility denials, assignment of the agreement to
      parties that are vaguely defined "affiliates," and offsets on future payments.
      These changes are essential to protecting your practice against unfavorable
      provisions that, left unchanged, put the payors in the driver's seat to decide
      the rules.

PMID- 19174972
TI  - Associate physician selection: perception & reality.
AB  - Whatever real or perceived margin for error without consequence in associate
      physician selection there has been in the past is now one. Reasons include the
      indisputable fact that competition for first- and second-tier associates
      continues to escalate with no end in sight. It is, therefore, a rational
      conclusion that the options for practices that do not become organized to get
      associate selection right the first time will be limited and could include
      arrival at a destination not envisioned. This article addresses practice dynamics
      that trigger adverse associate selection and presents creative selection tactics-
      to get it right the first time.

PMID- 19174973
TI  - Trends in the consumer price index.

PMID- 19174974
TI  - What drives the value of a medical practice?
AB  - In a complex healthcare environment, it is important to understand what drives
      the value of a medical practice, how to balance regulatory and business goals,
      and how physicians can positively impact the value of their practice.

PMID- 19174975
TI  - U.S. economic downturn's impact.

PMID- 19174976
TI  - Laboratory reimbursement--competitive bidding and after.

PMID- 19174977
TI  - The doctorate in clinical laboratory science: a view of clinical practice
      development.

PMID- 19174978
TI  - Functional assessment of hospital laboratory packaging and shipping preparedness
      in New York State.
AB  - The 2006-2007 New York State (NYS) Hospital Laboratory Drill Series was
      implemented in order to test notification, referral and packaging and shipping
      (P&S) procedures at acute care hospital facilities (statewide, excluding New York
      City) that submit suspect bioterrorism (BT), chemical terrorism (CT), and/or
      pandemic influenza (Pan Flu) clinical specimens to the NYS Department of Health
      (DOH) Wadsworth Center for confirmatory testing. Results showed that 97% and 84%
      of hospital facilities had the ability to directly access the notification
      network and retrieve drill guidance, respectively. Most hospital laboratories
      (92%) demonstrated the ability to refer specimens to the Wadsworth Center
      laboratory. Evaluation of specimen submissions found that 68% of BT packages, 27%
      of Pan Flu packages, and 20% of CT packages arrived to the laboratory with no P&S
      deficiencies. It can be concluded that acute care hospital facilities in NYS are
      more prepared to refer and submit clinical specimens during a BT public health
      emergency than during a Pan Flu or CT emergency event.

PMID- 19174980
TI  - Inherited bleeding disorders: a 14-year retrospective study.
AB  - Congenital bleeding disorders comprise a heterogeneous group of diseases that
      reflect abnormalities of blood vessels, coagulation proteins, and platelets. A 14
      year retrospective study (1991-2005) was conducted for patients referred to the
      coagulation section of the Hematology Department (King Hussein Medical Center,
      Amman, Jordan), who had suffered from bleeding tendencies to assess the
      prevalence of bleeding disorders among Jordanians and to describe their clinical
      manifestations. Four hundred and three patients matched our criteria. All
      patients were screened with routine coagulation assays and a complete blood cell
      count; a factor assay was performed if indicated by the results of the screening
      assays. A total of 168 patients (41.6%) were diagnosed with a bleeding disorder
      caused by a factor deficiency, of which 17.1% were described as hemophilia A
      (n=69), 6.2% were described as vWD (n=25), and 4.2% were described as hemophilia
      B (n=17). A subset of the total patient population comprising 14.1% of the
      patients were diagnosed with a Rare Inherited Coagulation Deficiency (RICD),
      where 4.0% were FX deficient (n=16), 3.7% were FVII deficient (n=15), 3.7% were
      FV deficient (n=15), 2.5% were FXI deficient (n=10), and 0.2% were diagnosed with
      afibrinogenemia (n=1).

PMID- 19174979
TI  - Septicemic arthritis with antibiotic resistance: a case study.
AB  - This article demonstrates how rheumatoid arthritis can be confused with
      septicemic arthritis. Effective diagnosis and treatment depends on timely and
      effective confirmation of the cause for arthritis. In the future, if such a case
      were presented, actions must be taken as soon as the bacteremia has been
      confirmed since the organism is the primary cause of the inflammation and not
      rheumatoid arthritis. If this is done immediately, the patient's body will be
      more effective at fighting off nosocomial infections resulting in a better
      prognosis.

PMID- 19174981
TI  - Evaluation of lancets for pain perception and capillary blood volume for glucose
      monitoring.
AB  - OBJECTIVE: The purpose of this study was to assess patient pain perception and
      capillary blood volume of four currently marketed lancets [BD Microtainer Contact
      Activated Lancet, Low Flow (Contact-Activated Lancet); LifeScan OneTouch SureSoft
      Gentle (OneTouch SureSoft Gentle); BD Genie Blue; SurgiLance Safety] in a
      diabetic population following routine finger-puncture procedures and glucose
      monitoring. METHODS: Data were collected from adult subjects diagnosed with type
      I or type II diabetes mellitus at a 300-bed US hospital following finger-puncture
      procedures for glucose monitoring. Based on quantitative and qualitative
      measurements, each blood collection device was evaluated for pain perception and
      calculated total capillary blood volume. RESULTS: A total of 80 subjects received
      four skin punctures in an alternating finger and hand sequence using each lancet.
      The ten clinicians (nurses and phlebotomists) conducted the study, collected and
      then calculated total capillary blood volume. It was determined that the Contact
      Activated Lancet produced less perceived pain and bleeding, while obtaining an
      adequate capillary blood volume for glucose monitoring. CONCLUSION: This study
      demonstrated that the Contact-Activated Lancet provided an adequate sample volume
      required for blood glucose monitoring. In addition, less perceived pain was
      elicited with this lancet when compared with the other lancets evaluated in the
      study.

PMID- 19174982
TI  - A quality improvement cycle: hemolyzed specimens in the emergency department.
AB  - OBJECTIVE: To determine the cause of and possible solution for an excessive
      number of hemolyzed specimens received from the emergency department (ED) of a
      large medical center. DESIGN: The clinical laboratory staff collected data on
      hemolyzed specimens for all departments of the medical center. The clinical
      laboratory management team and ED management team intervened with training and
      surveillance of the ED staff to heighten the awareness of the problem. SETTING:
      The clinical chemistry laboratory of a large medical center. MAIN OUTCOME
      MEASURE: The number of specimens submitted by inpatient departments and the ED
      was measured in relationship to the number ofhemolyzed specimens received from
      the departments. The clinical laboratory measured specimen processing times and
      turnaround times to determine their role in possibly contributing to the large
      number of hemolyzed specimens. Direct observation by a certified phlebotomist
      documented anecdotal evidence of the ED staffs phlebotomy practices. ED and
      clinical laboratory practitioners communicated realistic impressions of the
      medical centers problem with hemolyzed specimens. RESULTS: The laboratory
      processing times were not responsible for the hemolyzed specimens. The collection
      equipment was not responsible for the hemolyzed specimens. The ED had an
      excessive number ofhemolyzed specimens when compared to the rest of the medical
      center. The collection techniques in the ED appeared to be the origin of the
      problem. CONCLUSION: The intervention of the laboratory manager with the ED chief
      and nurse manager abated some of the professional arrogance between the
      departments. The dialogue educated the staffs about specific data that pointed to
      a possible origin of the problem. The ED chief placed his department on
      surveillance against problematic draws. Communication was improved between the
      two departments. However, only a moderate improvement in the number of hemolyzed
      specimens was noted. More training of medical center departments in phlebotomy
      and periodic proficiency evaluation of the all staff was indicated as a possible
      long-term solution.

PMID- 19174983
TI  - Occurrence and detection of iron-deficiency anemia in infants and toddlers.
AB  - Infants and toddlers are particularly vulnerable to developing iron deficiency,
      which can cause irreversible deficits in neurodevelopment. Children at highest
      risk include premature and low birth weight infants, those who are fed cow's milk
      rather than breast milk or formula prior to age one, and those who drink large
      amounts of cow's milk as toddlers. It is important to detect iron deficiency
      before it becomes frank anemia through the use of appropriate laboratory tests.
      Hemoglobin or hematocrit testing, at around age one, has been the usual screening
      test. These tests, however, do not become abnormally low until frank anemia has
      developed. Over the past decade, research has shown the assay for reticulocyte
      hemoglobin content to be a much earlier indicator of iron deficiency. This
      article provides an overview of the epidemiology, occurrence, and detection of
      iron deficiency and iron deficiency anemia in young children as well as a
      comparison of the utility of various laboratory tests.

PMID- 19174984
TI  - Anemia in an aging population.

PMID- 19174985
TI  - Pathophysiology of compound heterozygotes involving hemoglobinopathies and
      thalassemias.

PMID- 19174986
TI  - Insect taste. Preface.

PMID- 19174987
TI  - Gustation in Drosophila melanogaster.

PMID- 19174988
TI  - Drosophila Gr5a: expression pattern, ligand profile and transduction pathway.

PMID- 19174990
TI  - Chemosensory regulation of feeding in the blowfly: several studies after 'the
      Hungry Fly'.

PMID- 19174989
TI  - Neurophysiology of gustatory receptor neurones in Drosophila.

PMID- 19174991
TI  - Tasting in plant-feeding insects: from single compounds to complex natural
      stimuli.

PMID- 19174992
TI  - Tasting toxicants as bitter: phytoecdysteroids.

PMID- 19174993
TI  - Peripheral modulation of taste responses.

PMID- 19174994
TI  - The 'sweet tooth' of the honeybee: the perception of nectar and its influence on
      honeybee behaviour.

PMID- 19174995
TI  - Effects of experience on the physiology of taste discrimination in insects.

PMID- 19174996
TI  - Evolutionary biology of learning in insects: the search for food.

PMID- 19174998
TI  - [Renal solitary fibrous tumor with hemangiopericytoma-like pattern--a case
      report].
AB  - A 67-year-old man was referred to our clinic with a complaint of macroscopic
      hematuria. He had been treated for schizophrenia in a psychology ward. Computed
      tomography (CT) scan revealed a left renal tumor 7 cm in size, well enhanced in
      early phase. Doppler ultrasonography indicated hypervascular left renal tumor.
      Laparoscopic radical left nephrectomy was performed under the diagnosis ofrenal
      cancer. Histopathlogical results showed a renal solitary fibrous tumor (SFT) with
      a hemangiopericytoma-like pattern. Renal SFT is an uncommon tumor. The present
      case is the 11th reported case of SFT with hemangiopericytoma-like pattern in the
      Japanese literature.

PMID- 19174999
TI  - [Extraskeletal myxoid chondrosarcoma of the left iliopsoas muscle].
AB  - A 62-year-old man was referred to our hospital with a 10 cm retroperitoneal
      tumor, which was incidentally found on the abdominal computed tomography (CT). CT
      guided percutaneous needle biopsy revealed that the tumor was malignant, but
      could not define the exact pathology of the tumor. The tumor was resected. The
      pathological study revealed atypical spindle to polygonal shaped cells embedded
      in the myxomatous stroma. The tumor was diagnosed as extraskeletal myxoid
      chondrosarcoma. Walking difficulty was observed postoperatively, which was
      considered to have been caused by damage of a branch of the femoral nerve. The
      difficulty had gradually overcome with rehabilitation before discharge.

PMID- 19174997
TI  - [Multi-center trial on the early effects of silodosin on lower urinary tract
      symptoms associated with benign prostatic hyperplasia].
AB  - Silodosin (URIEF), a new so-called 3rd generation alpha-1 blocker, is widely
      expected to be effective and useful for lower urinary tract symptoms (LUTS)
      associated with benign prostatic hyperplasia (BPH), due to its high specificity
      to alpha-1A receptor. We evaluated the efficacy of Silodosin, on 187 males 50
      years old or over with the diagnosis of BPH. Silodosin significantly improved the
      International Prostate Symptom Score (IPSS) and quality of life (QOL) score from
      the day after administration was started. Among 166 patients whose data were
      available for the analysis of efficacy of Silodosin, 77.5% showed apparent
      subjective improvement. Eighty three patients, who had been taking another alpha
      1 blocker but without satisfactory effects, showed almost the same improvements
      in IPSS and QOL score after switching to Silodosin as the remaining 83 patients
      who had no preceding treatment with an alpha-1 blocker. The improvements were not
      only in voiding symptoms but also in storage symptoms. The patients, who had
      serious storage symptoms, responded rather well to Silodosin and showed
      significant improvement. Taken together, Silodosin showed a quick effect for
      improving subjective symptoms and QOL, and was found to be useful for the
      management of LUTS with BPH.

PMID- 19175000
TI  - [Urinary bladder cancer producing granulocyte-colony stimulating factor: a case
      report and review of the literature].
AB  - We report a case of urinary bladder cancer that produced granulocyte-colony
      stimulating factor (G-CSF). A 56-year-old man was admitted to our hospital with
      the chief complaint of macroscopic hematuria. Cystoscopy demonstrated a thumb tip
      sized bladder tumor. Computerized tomography and magnetic resonance imaging
      showed muscular invasion in the bladder, but no distant metastases. The complete
      blood count and laboratory examination showed leukocytosis of 25,200/mm3 and a
      high G-CSF level of 145 pg/ml in the peripheral blood. Although he underwent
      total cystectomy and adjuvant chemotherapy using methotrexate, vinblastine,
      doxorubicin and cis-platinum (M-VAC) under the diagnosis of locally advanced
      bladder cancer, he died of progressive disease of the carcinoma about eight
      months after the diagnosis. A temporary decrease of white blood cell count and
      serum GCSF were observed just after treatment. The histopathological diagnosis
      was undifferentiated giant and spindle cell carcinoma of the urinary bladder
      (grade 3, pT3b, pN1). The tumor cells exhibited positive staining for G-CSF
      immunohistochemically.

PMID- 19175001
TI  - [Squamous cell carcinoma of the bladder presenting with spontanenous
      intraperitoneal bladder rupture: a case report].
AB  - A-90-year-old woman visited complaining of nausea, vomiting, and abdominal pain.
      She had abdominal rigidity and signs of generalized peritonitis. On computed
      tomography (CT) gastrointestinal perforation was denied and irregular thickness
      of the bladder wall was pointed out. Cystography was performed, but bladder
      rupture was not confirmed. Post-cystogram-CT revealed the leakage of contrast
      material in the peritoneal cavity from the urinary bladder. Spontaneous
      intraperitoneal bladder rupture was diagnosed. Cystoscopy was performed, but no
      information could be obtained due to severe cloudy urine. Open laparotomy was
      performed. At surgery, cloudy fluid was aspirated from the abdominal cavity.
      Abdominal organs were normal when explored, but a small perforation was found on
      the vault of the bladder and primary closure was performed. Postoperatively,
      cystoscopy was performed again after the medication with antibiotics. A huge,
      nonpapillary tumor was seen on the left lateral wall. Tumor biopsy was performed.
      Histological examination of specimens revealed squamous cell carcinoma. On
      abdominal CT, invasive bladder carcinoma, left hydronephrosis and hydroureter
      were pointed out. Considering her age, general health status and prognosis, only
      right ureterocutaneostomy was performed.

PMID- 19175002
TI  - [Regression of mucosa-associated lymphoid tissue lymphoma of the bladder after
      antibiotic therapy: a case report].
AB  - A 69-year-old woman presented with macroscopic hematuria and severe anemia.
      Cystoscopy revealed flat edematous mucosa with continuous bleeding. Transurethral
      coagulation and a biopsy of the urinary bladder were performed. Histopathological
      examination of the biopsy revealed non-Hodgkin's lymphoma of the mucosa
      associated lymphoid tissue (MALT) type. Results of a computed tomography scan and
      gallium scintigraphy suggested that it was a primary malignant lymphoma of the
      urinary bladder. A urinary tract infection was found and she was treated with
      antibiotics for 2 weeks. Because of the detection of a Helicobacter pylori (HP)
      infection in the gastric mucosal biopsy specimens, the patient was subsequently
      administered HP eradication therapy. Consequently, the lymphoma disappeared and
      the woman has had no tumor recurrence for the past 25 months.

PMID- 19175003
TI  - [Metastatic malignant melanoma of the urinary bladder presenting with hematuria:
      a case report].
AB  - A 65-year-old man complained of macroscopic hematuria and urinary obstruction. A
      blood clot in the bladder eliminated transurethrally demonstrated a solitary
      tumor at the dome of the bladder. Transurethral resection of the bladder tumor
      (TUR-Bt) was performed, and histological diagnosis was malignant melanoma.
      Physical examination revealed a black-pigmented site on the lateral border of the
      right foot sole, which was dermatologically diagnosed as malignant melanoma. The
      vesical site was diagnosed as a metastatic melanoma of the bladder. Metastatic
      neoplasms of the bladder are rare, ranging from 0.1 to 6.2 percent of all bladder
      tumors. To our knowledge, approximately forty percent of metastatic neoplasms of
      the bladder originate from melanoma. Therefore, an atypical nodular lesion
      encountered during cystoscopy may be metastasis of malignant melanoma and
      dermatic lesions should be investigated.

PMID- 19175004
TI  - [Acquired male hypogonadotropic hypogonadism (MHH) in a patient with empty sella:
      a case report].
AB  - A 40-year-old unmarried male was referred to our hospital with anejaculation. His
      secondary sex characteristics, sexual function and ejaculation were previously
      normal but for the last 5 years he found it impossible to ejaculate even though
      he could achieve an erection. His genital stage was Tanner V, and pubic hair
      stage was Tanner III. There were no varicoceles or chromosomal aberrations. His
      testis volume was 10 ml on the right side and 12 ml on the left. His hormonal
      data were luleinizing hormone (LH) 0.3 mIU/ml (normal: 2.2-8.4 mIU/ml), fillicle
      stimulating hormone (FSH) 1.5 mIU/ ml (1.8-12 mIU/ml), testosterone 0.05 ng/ml
      (2.01-7.5 ng/ml). A gonadtropin releasing hormone (GnRH) test and human chorionic
      gonadotropin (hCG) stimulation test revealed low responses of LH, FSH and a
      normal response of testosterone. Magnetic resonance imaging of the head revealed
      slight depression of the diaphragma sellae, indicating an "empty sella". We
      diagnosed acquired hypogonadtropic-hypogonadism related empty sella. An hCG
      replacement therapy was introduced and after 3 months the patient's capacity to
      ejaculate was restored and testis volume was 14 ml on both sides. Six months
      after hormone replacement therapy, semen analysis revealed azoospermia. Then we
      added r-hFSH to his treatment and expect his sperm to reappear.

PMID- 19175005
TI  - [A case of metastatic tumor of penis from esophageal carcinoma].
AB  - We report a 68-year-old man with a metastatic tumor of the penis originating from
      an esophageal carcinoma that had been removed two years ago. Multiple metastases
      were present on the liver, brain, eye and penis for the past year. He consulted
      with our department complaining of severe penile pain and dysuria. Solid masses
      were palpated in the penile sponge and the ventral glans was necrotic.
      Histological examinations indicated a metastatic squamous cell carcinoma. A total
      penectomy was performed for the purpose of managing local symptoms. Following
      operation, the penile pain improved; however, he died three months after the
      operation.

PMID- 19175006
TI  - [A case of neonatal testicular torsion].
AB  - An infant normally delivered at the 38th week of gestation was referred to our
      department one day after birth for a firm and painless right hemiscrotal mass
      with bluish coloration. Since contralateral scrotum showed swelling, we performed
      emergency surgery on that day. The right spermatic cord was constricted due to
      extravaginal torsion, and degree and direction of torsion was unclear since the
      spermatic cord was already organized. Right testis showed irreversible necrotic
      change, requiring orchiectomy. We confirmed that left testis was intact and
      performed orchidopexy. Since high incidence of contralateral asymptomatic torsion
      has been reported in patients with prenatal testicular torsion, emergency surgery
      should be considered when contralateral scrotum shows abnormal findings.

PMID- 19175007
TI  - [Three case reports of metastatic germ cell tumors in the lumbar vertebra during
      first-line chemotherapy].
AB  - We report three patients with germ cell tumors whose diagnosis was confirmed in
      the progress of the first-line chemotherapy regimen as metastatic cancer in the
      lumbar vertebra. Two of the 3 cases were mixed-type nonseminoma, and the other
      case was an extragonadal tumor. After the first-line chemotherapy regimen, the
      patients underwent salvage chemotherapy using Paclitaxel either with or without
      irradiation. We confirmed the efficacy that the bone metastasis had completely
      been resolved and the lymph node metastasis was significantly reduced after the
      completion of all treatments.

PMID- 19175008
TI  - [Sex differences and anesthesiology: preface and comments].
AB  - In this special issue, the topic of sex difference in the field of anesthesiology
      is featured. Eight subtopics are discussed including 1) sex differences in
      cardiovascular medicine, 2) perioperative cardiovascular management, 3) sex
      differences in the respiratory functions of the upper airway, 4) sex differences
      in the anesthetic management, 5) sex differences in pain, 6) sex differences in
      laboratory medicine, 7) sex differences in pharmacokinetics of anesthetics, and
      8) postoperative nausea and vomiting. Although recent clinical and experimental
      studies have shown the existence of sex and/or gender differences in many fields
      of medicine, our knowledge of sex differences in anesthesiology is apparently
      insufficient. I believe that anesthesiologists should pay more attention to this
      topic to improve our daily practice of anesthesia.

PMID- 19175009
TI  - [Sex and gender differences in cardiovascular medicine].
AB  - Obvious gender differences exist in the incidence of cardiovascular disease.
      Atherosclerotic disease such as coronary artery disease and stroke are more
      prevalent in men, but some types of arrhythmia such as long QT syndrome are more
      prevalent in women. Genetic differences and sex hormones may play a role.
      Particularly, estrogen can exert protective effects against the cardiovascular
      and metabolic system. Gender differences in life style and sociomedical behavior
      may play some role.

PMID- 19175010
TI  - [Perioperative cardiovascular management in consideration of gender differences].
AB  - Several clinical and experimental studies have demonstrated gender differences in
      cardiovascular physiology and pharmacology. Male subjects have greater baroreflex
      sensitivity than female. Prolonged hypertensive reactions after adrenergic
      stimulation are observed in male patients. Although female subjects demonstrate
      low cardiac risk factors before menopause, elderly women have a higher prevalence
      of morbidity after coronary artery bypass surgery. In experimental articles,
      female sex steroids appear to exhibit immunoprotective properties following
      trauma and severe blood loss. Gender difference, thus, is an essential factor for
      tailor-made medicine. Further investigations are necessary to establish the
      better cardiovascular management in consideration of gender differences.

PMID- 19175011
TI  - [Gender difference in the respiratory functions of the upper airway].
AB  - Gender differences could exist in the respiratory functions of the upper airway,
      especially when they relate to sleep and possibly sleep apnea. Particular
      attention should be given to factors related to upper airway patency, considering
      the gender difference of anesthesia. The pharyngeal airway is open during
      wakefulness but occludes during sleep implicating a neural component dependent
      upon state of vigilance, although anatomical upper airway narrowing in the
      genesis of airway occlusion during sleep plays an important role. Respiratory
      disturbances, including sleep apnea syndromes, are less common in women than men
      until after menopause. Particularly marked is the male predominance among
      patients with obesity hypoventilation syndrome. While obesity increases the risk
      of developing sleep-disordered breathing in both sexes, women with sleep apnea
      syndromes are more massively obese than their male counterparts. Several factors
      may contribute to the protection in herento premenopausal women, including the
      presence of female hormones, the absence of male hormones, and the effects of
      gender or age unrelated to sex hormones. These factors, in turn, appear to
      influence airway patency and ventilatory control.

PMID- 19175012
TI  - [Gender differences in anesthesia management].
AB  - Men and women have different body compositions such as fat and fluid, and
      hormonal environments which affect both pharmacokinetics and pharmacodynamics of
      anesthesia-related drugs. The knowledge on gender differences in the effects of
      these drugs has been accumulated. We firstly focus on gender differences in the
      depth of anesthesia, intraoperative awareness and emergence from anesthesia.
      Then, gender differences in the effects of commonly used anesthesia-related
      agents are discussed. Although there have not been remarkable differences
      demonstrated, better understanding of the difference may lead to satisfying
      perioperative anesthetic cares for each sex.

PMID- 19175014
TI  - [Sex differences in the field of laboratory medicine].
AB  - It is well-known that there are significant "sex differences" in many laboratory
      tests. After puberty onset, sex-specific organs are well developed and clinical
      tests concerning their functions show obvious sex differences. On the other hand,
      sex differences are minimal or negligible in other test items representing
      functions of organs common in the both sexes. But, there are some exceptions.
      While in childhood, sex steroids secretions from sex-specific organs are
      inhibited in both sexes, after puberty onset, differences in the amount of
      secretion of sex steroids increase, resulting, either in a direct or indirect
      ways, in sex differences of the blood levels of many laboratory tests. The
      mechanisms of sex differences are not clear in many test items. Indeed, sex
      difference in height is not necessarily completely unraveled. Further studies on
      mechanisms of sex differences in laboratory tests will reveal mysterious
      differences between men and women.

PMID- 19175013
TI  - [Sex and/or gender differences in pain].
AB  - Evidence about sex and gender differences in pain and analgesia has been gathered
      rapidly during the past decade. A number of studies have demonstrated a higher
      prevalence of pain states and greater pain sensitivity among women compared with
      men. Sex hormones influence pain sensitivity. Activity of cytochrome P450 in
      female is greater than in male and this suggested that drugs are more rapidly
      metabolized in female than in male. Analgesic effect of pentazocine is reported
      to be more potent in male than in female. These data strongly suggested that
      males and females may have different pain modulatory circuits. Continued research
      at the genetic and receptor levels may support to develop gender-specific
      therapies.

PMID- 19175015
TI  - [Gender differences in pharmacokinetics of anesthetics].
AB  - The gender aspect in pharmacokinetics and pharmacodynamics of anesthetics has
      attracted little attention. Knowledge of previous work is required to decide if
      gender-based differences in clinical is justified. Females have 20-30% greater
      sensitivity to the muscle relaxant effects of vecuronium and rocuronium. When
      rapid onset of or short duration of action is very important, gender-modified
      dosing may be considered. Males are more sensitive than females to propofol. It
      may therefore be necessary to decrease the propofol dose by 30-40% in males
      compared with females in order to achieve similar recovery times. Females are
      more sensitive than males to opioid receptor agonists, as shown for morphine as
      well as for pentazocin. On the other hand, females may experience respiratory
      depression and other adverse effects more easily if they are given the same doses
      as males. These examples illustrate that gender should be taken into account as a
      factor that may be predictive for the dosage of several anesthetic drugs.
      Moreover, there is an obvious need for more research in this area in order to
      further optimize drug treatment in anesthesia.

PMID- 19175016
TI  - [Postoperative nausea and vomiting and their sex differences].
AB  - Postoperative nausea and vomiting (PONV) are two of the commonest and most
      distressing complications of general anesthesia and surgery. Factors affecting
      PONV are patient characteristics, surgical procedure, anesthetic technique, and
      postoperative care. Female patients have 1.5-3 times greater incidence of PONV
      than males, due to increased plasma progesterone levels during their menstrual
      cycles. However, the exact reason for this difference is unknown. Most of
      published trials indicate improved prophylaxis against PONV by avoiding risk
      factors and/or by using effective antiemetic therapy (e. g., traditional and non
      traditional antiemetics, serotonin receptor antagonists). Non-pharmacotherapy (e.
      g., P6 acupressure) is also important. Knowledge regarding prophylactic
      antiemetic therapy is necessary to management of PONV in female patients.

PMID- 19175017
TI  - [Curve-fit with hybrid logistic function for intracellular calcium transient].
AB  - As the left ventricular (LV) pressure curve and myocardial tension curve in heart
      are composed of contraction and relaxation processes, we have found that hybrid
      logistic (HL) function calculated as the difference between two logistic
      functions curve-fits better the isovolumic LV pressure curve and the isometric
      twitch tension curve than the conventional polynomial exponential and sinusoidal
      functions. Increase and decrease in intracellular Ca2+ concentration regulate
      myocardial contraction and relaxation. Recently, we reported that intracellular
      Ca2+ transient (CaT) curves measured using the calcium-sensitive bioluminescent
      protein, aequorin, were better curve-fitted by HL function compared to the
      polynomial exponential function in the isolated rabbit RV and mouse LV papillary
      muscles. We speculate that the first logistic component curve of HL fit
      represents the concentration of the Ca2+ inflow into the cytoplasmic space, the
      concentration of Ca2+ released from sarcoplasmic reticulum (SR), the
      concentration of Ca2+ binding to troponin C (TnC), and the attached number of
      cross-bridge (CB) and their time courses, and that the second logistic component
      curve of HL fit represents the concentration of Ca2+ sequestered into SR, the
      concentration of Ca2+ removal from the cytoplasmic space, the concentration of
      Ca2+ released from TnC, and the detached number of CB and their time courses.
      This HL approach for CaT curve may provide a more useful model for investigating
      Ca2+ handling, Ca(2+) -TnC interaction, and CB cycling.

PMID- 19175018
TI  - [Comparative study of anesthesia with remifentanil VS fentanyl in terms of
      postoperative pain and shivering].
AB  - BACKGROUND: Remifentanil is reported to be cleared rapidly more than other any
      opioids. It is considered that this characteristic may lead to an increase in
      postoperative pain and shivering after general anesthesia with remifentanil. This
      study was aimed to examine the influence of remifentanil to these adverse
      symptoms in comparison with fentanyl. METHODS: The subjects consisted of 41
      female patients having undergone a total intravenous anesthesia with remifentanil
      or/and fentanyl for gynecological laparoscopic surgery. RESULTS: There was no
      significant difference in the occurrence of postoperative pain. Shivering
      occurred significantly more frequently in patients who had received remifentanil
      anesthesia, associated with a significant lower body temperature after general
      anesthesia. CONCLUSIONS: Careful management of intraoperative body temperature is
      important to prevent the occurrence of shivering after total intravenous general
      anesthesia with remifentanil.

PMID- 19175019
TI  - [Comparison of the changes in blood glucose levels during anesthetic management
      using sevoflurane and propofol].
AB  - BACKGROUND: Recent studies have shown that sevoflurane impairs glucose tolerance,
      but the effect of propofol on glucose metabolism is not still clear. METHODS: Two
      hundred and seventeen patients were enrolled in this retrospective study.
      Patients were classified into two groups according to anesthetic agent used for
      maintenance of general anesthesia; sevoflurane group (n = 154) and propofol group
      (n = 63). Changes in blood glucose levels were compared between the two groups in
      four periods during anesthetic management ; within 1 hour, 1-2 hour, 2-3 hour, 3
      4 hour after the induction of general anesthesia. RESULTS: The two groups were
      comparable with regard to patients' age, gender, height, weight, and American
      Society of Anesthesiologists physical status. In all time periods, blood glucose
      level in sevoflurane group was significantly higher than that in propofol group.
      CONCLUSIONS: Results in this study imply that the effect on glucose metabolism of
      propofol is much less than that of sevoflurane.

PMID- 19175020
TI  - [Anesthetic management using epidural anesthesia and dexmedetomidine for
      thoracoscopic lung resection in a patient with compromised lung functions].
AB  - A 59-year-old man with poor pulmonary functions was scheduled for thoracoscopic
      lung resection because of right pneumothorax. In order to preserve spontaneous
      breathing and prevent left pneumothorax, we selected epidural anesthesia and
      intravenous dexmedetomidine. We could provide appropriate sedative and
      antianxiety effect without respiratory depression and hemodynamic change. With
      its unique features, dexmedetomidine is useful for thoracoscopic surgery in a
      patient with poor lung functions.

PMID- 19175021
TI  - [Management of anesthesia with artificial pancreas STG-22 for pheochromocytoma
      resection].
AB  - A 74-year-old woman underwent radical nephrectomy for an adrenaline predominant
      pheochromocytoma in the left adrenal gland. She was pretreated with doxazosin for
      3 weeks before surgery. Anesthesia was induced with intravenous fentanyl,
      midazolam and vecuronium, and inhaled sevoflurane in oxygen. A central venous
      catheter was inserted into the right internal jugular vein and a PiCCO catheter
      was inserted into the femoral artery for the monitoring of cardiac function and
      hemodynamics. In addition, continuous monitoring and automatic control of blood
      glucose were started using STG-22. Target concentration of blood glucose was set
      at 120-140 mg x dl(-1). Anesthesia was maintained with sevoflurane and
      remifentanil. Prostaglandin E1, nitroglycerin and dexmedetomidine were infused
      continuously from the start of surgery, and the systolic blood pressure was kept
      within 120-160 mmHg. During surgical manipulation around the tumor, there were
      sudden increases in blood pressure, heart rate and blood glucose concentration.
      Thus, phentolamine and landiolol were also administered to control blood pressure
      and heart rate. On the contrary, after the tumor removal, noradrenaline,
      dobutamine and milrinone were required to maintain blood pressure. The STG-22
      worked well to maintain blood glucose concentrations during surgery without any
      hyper- and hypoglycemic events.

PMID- 19175022
TI  - [Effects of percutaneous lidocaine administration and xenon-ray irradiation on
      post-herpetic neuralgia in liver transplant recipients: a report of three cases].
AB  - We report three cases of liver transplant recipients (LTRs) with postherpetic
      neuralgia (PHN). They were referred to our department because of poor pain
      control. Repeated percutaneous lidocaine (2%, 15 ml) administration to the site
      of the pain via an iontophoresis system and xenon-ray irradiation were effective
      for the three patients. Visual analogue scale for pain decreased significantly
      and requirements of analgesics diminished considerably during the therapy without
      serious side effects. PHN is relatively common in LTRs, but treatment options are
      restricted because of immunosuppressive therapy and hepatic and/or renal
      dysfunction. However noninvasive frequent iontophoretic administration of
      lidocaine and xenon-ray irradiation produced satisfactory pain relief for PHN in
      LTRs.

PMID- 19175023
TI  - [Anesthetic management for nephrectomy using a monopolar electrocautery in a
      patient implanted with a biventricular pacemaker].
AB  - A 72-year-old man implanted with a biventricular pacemaker was diagnosed
      pyonephrosis, and left nephrectomy was performed under general and epidural
      anesthesia. Urologists were going to use a monopolar electrocautery during the
      operation. Before the operation, we attempted to convert the pacemaker from DDD
      mode to DOO mode with a precordial magnet because we wanted to know the effect of
      DOO mode in this patient implanted with a biventricular pacemaker and how a
      monopolar electrocautery interfered the biventricular pacemaker. His blood
      pressure and heart rate were stable during DOO mode by a precordial magnet, but
      the stroke volume was reduced a little. Then, we suggested surgeons the minimal
      use of the monopolar electrocautery. Actually, intraoperative use of the
      monopolar electrocautery did not interfere his pacemaker, and the operation was
      completed uneventfully. Recently in Japan, cardiac resynchronization therapy
      (CRT) becomes more common and operations in the patients implanted with
      biventricular pacemakers will become more frequent. The surgeons and
      anesthesiologists should take in mind that the monopolar electrocautery is
      appropriate or not depending on the individual patient.

PMID- 19175024
TI  - [Comparison of performance of endotracheal intubation by senior residents in
      anesthesiology using Airway Scope VS Macintosh laryngoscope].
AB  - BACKGROUND: To evaluate the performance of the Airway Scope, we studied the time
      to complete endotracheal intubation performed by senior residents in
      anesthesiology. METHODS: The trachea of the patient was intubated using the
      Airway Scope (n = 90) or the Macintosh laryngoscope (n = 81). RESULTS: The time
      to complete endotracheal intubation was 42 +/- 23 sec with the Airway Scope and
      41 +/- 20 sec with the Macintosh laryngoscope. CONCLUSIONS: The Airway Scope
      performed as well as the Macintosh laryngoscope when used by senior residents in
      anesthesiology on patients with normal airway.

PMID- 19175025
TI  - [Case report : respiratory care for anesthesia in a patient with Menkes syndrome
      and micrognathia].
AB  - Menkes disease is a rare sex-linked disorder of copper metabolism, characterized
      with several multiple organ dysfunctions. It is frequently associated with
      seizure disorders, mental retardation, and urologic abnormalities. It may also
      have some serious respiratory complications, such as upper airway obstruction
      related to micrognathia, risks of gastroesophageal reflux and the aspiration with
      poor pharyngeal muscle control, and hazard to easy cerebral bleeding to noxious
      stimuli and easy fracture of the bones. We report a 1 year and 10 month-old boy
      of Menkes disease with a large bladder diverticulum associated with persistent
      urinary tract infections who required the surgical treatment. Cystostomy was
      scheduled and performed under general anesthesia. In the preoperative
      examination, three-dimentional computed tomography images were essential and very
      useful for preanesthetic anatomical evaluation of the upper airway, which
      revealed subglottic narrowing with micrognathia. Considering the anticipated
      difficulty of the tracheal intubation, and to avoid or minimize the noxious
      stimuli related to the intubation, we had chosen to use laryngeal mask airway,
      which provided an appropriate, safe anesthetic respiratory care in this case.

PMID- 19175026
TI  - [Case of pulmonary edema and transient heart failure during difficult airway
      management].
AB  - Many kinds of side effects are likely to occur while managing difficult airway.
      This article describes a case of a man who fell into pulmonary edema and heart
      failure during the difficult airway management. He was to undergo arthroscopic
      surgery on his knee. At first, we planed spinal anesthesia but he took an
      antiplatelet drug (aspirin). Since we wanted to avoid the epidural hematoma, we
      chose general anesthesia. After induction of general anesthesia, positive
      pressure ventilation via face mask was possible, but laryngeal mask ventilation
      was impossible. Although tracheal intubation was attempted, we recognized that he
      had difficult airway. After some intubation trials, we decided to quit the
      operation and awoke the patients. Spontaneous breathing appeared soon, but the
      oxygenation was getting worse. We performed fiberoptic nasal intubation under
      spontaneous breathing. Although his blood pressure was quite high during
      intubation, after intubation the vasopressor was needed to maintain blood
      pressure. Ventilation with 100% O2 could not maintain the oxygenation well. Chest
      X-ray revealed the pulmonary edema. We presumed that hypertension associated with
      airway stimulation had caused acute pulmonary edema and heart failure resulting
      from diastolic dysfunction induced by increased catecholamine.

PMID- 19175027
TI  - [Present status of preparatory measures for massive hemorrhage and emergency
      blood transfusion in regional hospitals with an accredited department of
      anesthesiology in 2006].
AB  - BACKGROUND: Annual surveys conducted by the Japanese Society of Anesthesiologists
      repeatedly show that hemorrhage is the leading cause of life-threatening events
      in the operating room. METHODS: We performed a questionnaire survey regarding the
      present status of critical hemorrhage/ blood transfusion occurring in the
      operating room on an institutional scale and individual blood transfusion
      management in cases of massive hemorrhage (> or = 5,000 ml) in hospitals with >
      or = 500 beds and those with an accredited Department of Anesthesiology regarded
      as regional hospitals. RESULTS: Of 384 institutions, 247 responded to the
      questionnaire (response rate: 64%), and 692,241 cases managed by
      anesthesiologists in 2006 were registered. There were 2,657 cases of massive
      hemorrhage above the circulating blood volume in the operating room, and 404 of
      them were critical. Thus, the number of cases of massive hemorrhage was 6.6 times
      that of cases of critical events due to hemorrhage. In the survey of individual
      cases of massive hemorrhage (> or = 5,000 ml), 1,257 cases were registered in
      2006, of whom 196 cases (15.6%) died within 30 post-operative days and 160 cases
      (12.7%) had some sequelae. The amount of transfused red blood cell concentrate
      was 25.2 +/- 24.2 units. The amount of red blood cell concentrates stocked for
      emergency was 12.7 +/- 10.1 units for blood group A, 9.7 +/- 7.3 units for group
      B, 11.9 +/- 9.6 group AB, and 11.3 +/- 11.0 for group O. Therefore, for those
      other than group O cases, 21-46 units of red blood cell concentrates seemed to be
      available in the hospital. The survey of individual cases showed uncross-matched,
      same blood group transfusion and compatible, different blood group transfusion
      were performed in only 8.2% and 4.3%, respectively. The lowest hemoglobin
      concentration was below 5 g x dl(-1) in 16.7% of the cases, but uncross-matched,
      same blood group transfusion was performed only in 19.0% and compatible,
      different blood group red cell concentrate transfusion in 5.2%. Even in cases who
      required cardiac massage, uncross-matched, same blood group transfusion was
      performed only in 17.1% and compatible, different blood group red cell
      concentrate transfusion in 8.5%. Intraoperative blood salvage was performed in
      only 5.7% in cases who underwent non-cardiac surgery. The "Guidelines for the
      Management of Critical Hemorrhage" proposed in 2007 or the manuals for in
      hospital emergency blood transfusion were insufficiently recognized, even by
      anesthesiologists, and rarely known by surgeons. There were no such manuals in
      more than 60% of the institutions. CONCLUSIONS: Undertransfusion may occur in
      16.7-28.3% of cases of massive hemorrhage in the operating room, and the rate of
      emergency blood transfusion was much lower than this percentage. To avoid
      operation-associated deaths from hemorrhage, the improvement of hospital systems
      for emergency blood transfusion, including the active use of intraoperative blood
      salvage, should be promoted.

PMID- 19175028
TI  - [Historical background and current status of hemispherotomy].

PMID- 19175029
TI  - [Surgical technique and neuropsychological outcome of transsylvian selective
      amygdalohippocampectomy preserving the limen insula in 70 patients with
      hippocampal sclerosis].

PMID- 19175030
TI  - [Multidisciplinary treatment for severe syndromic craniosynostosis].
AB  - We describe the treatment of patients having syndromic craniosynostosis with
      severe craniofacial abnormality. One patient had Cruzon's syndrome, one had Beare
      Stevenson cutis gyrata syndrome, and four had Pfeiffers syndrome. Anterior
      cranial deformity in all patients was treated using fronto-orbital advancement
      (FOA) by gradual distraction. Initially, the frontal and supraorbital bones were
      removed and remodeled. Next, the frontal bones were fixed loosely to the
      supraorbital bones with absorbable threads. Then, the supraorbital and temporal
      bones were connected using distraction devices on both sides. The temporal bones
      were thereafter reinforced with titanium plates. Distraction was started one week
      postoperation, and the mean amount of elongation was 28.9 mm. Distraction devices
      were removed one to five months after the operation. One case required FOA by the
      traditional method ten months after the initial operation. Local infection was
      observed in three cases, but there were no majors complications. Posterior
      cranial remodelings were performed in five cases, with one requiring a second
      operation. We chose the appropriate procedure according to the degree of cranial
      deformity and operative findings. We performed decompression of the foramen
      magnum in five cases and laminectomy of the atlas in two cases.
      Ventriculoperitoneal shunt for hydrocephalus and tracheotomy for airway
      obstruction were performed in all cases. Cranial remodeling for treating severe
      craniofacial abnormality requires careful inspection of abnormalities, proper
      timing, close attention to the procedure and adequate perioperative care.
      Multidisciplinary therapy is essential for treating severe syndromic
      craniosynostosis due to systematic osseocartilaginous aplasia.

PMID- 19175031
TI  - [Transposition technique of microvascular decompression for hemifacial spasm
      without using a brain retractor].
AB  - A unique transposition technique in microvascular decompression for hemifacial
      spasm (HFS) was employed in patients with compression by either the peripheral
      artery or the main trunk of the vertebral artery. Complete transposition that
      secured free space between the offending artery and the root exit zone (REZ) was
      accomplished by introducing GORE-TEX tape around the artery and suturing it to
      the petrous dura. An adequate working space, as if operating in a shallow basin,
      was essential. Throughout the procedure, it was not necessary to use a brain
      retractor. Instead, a gentle wrapping retraction technique using a sucker was
      employed over the brain covered by a sheet of Gelfoam (Pfizer Japan Inc., Tokyo)
      and cotton. All patients showed complete cure of HFS immediately after surgery
      with this technique. The difficulty of transposing the vertebral artery can be
      overcome by well-designed surgical strategy and skillfulness.

PMID- 19175032
TI  - [Technique for embedding a titanium miniplate in the forehead that avoids
      objectionable bulges].
AB  - OBJECTIVE: As the fixation of cranial bone flaps with titanium miniplates may
      produce esthetically objectionable bulges especially on the forehead covered with
      thin scalp, we developed a technique that solves this problem. PATIENTS AND
      METHODS: The study material consisted of 19 consecutive sides treated by
      frontotemporal cranioplasty using free bone flaps and miniplate-fixation. A pit
      matching the width and depth of the miniplate was drilled on the outer table, the
      miniplate was embedded in the pit in the forehead and fixed with screws. RESULTS:
      Fixation of the bone flap was successful on 18 sides. In one instance the outer
      table lost the strength to sustain the screws due to excessively deep drilling.
      No esthetically objectionable bulges were noted even in patients with a thin
      scalp cover. CONCLUSIONS: This simple technique avoids the development of bulges
      and provides satisfactory cosmetic results. The key to this technique is
      preservation of the outer table at the bottom of the pit (more than 1 mm in
      thickness) to assure the stability of the fixation screws.

PMID- 19175033
TI  - [Embolic complications by ink clots removed from syringes during cerebral
      angiography].
AB  - We noted, during cerebral angiography, that the contrast medium was contaminated
      with numerous small black ink clots from gradation marks on syringes. In this
      report, we show that ink can be removed from syringes in solid form, and that
      they may result in embolic complications during cerebral angiography. MATERIALS
      AND METHODS: To demonstrate that the ink from gradation marks on syringes can
      come off in a solid form and attach itself to the gloves during cerebral
      angiography, syringes were gripped many times (just as in an angiographic
      procedure) after immersion in contrast medium or 0.9% saline for 10 minutes. To
      see if difference of contrast medium and syringes could affect the removing of
      ink, five types of nonangiographic syringes and one type of angiographic syringe
      were rubbed with gauze after certain time periods after immersing them in four
      kinds of contrast medium or 0.9% saline. RESULTS: Ink attached itself to the
      gloves in a solid form by repeated gripping due to adherence of contrast medium.
      Ink was removed from all nonangiographic syringes by rubbing after immersion in
      any type of contrast medium for two hours. Gradation marks on angiographic
      syringes were stable with all types of contrast medium. CONCLUSIONS: Thus, ink
      for gradation marks on nonangiographic syringes, which is easily removed in a
      solid form due to contrast medium, can be the source of embolic complication
      during cerebral angiography.

PMID- 19175034
TI  - [Case of cerebral venous thrombosis causing refractory intracerebral hemorrhage].
AB  - Cerebral venous thrombosis is an uncommon disease characterized by expansive
      cerebral edema, venous infarction and massive intracerebral hemorrhage. Magnetic
      resonance imaging and angiography are useful for diagnosis of cerebral venous
      thrombosis. A 54-year-old man was admitted with headache, vomiting and right
      hemiparesis. Computed tomography (CT) revealed subcortical hematoma in the left
      parietal lobe. Digital subtraction angiography (DSA) demonstrated occlusion of
      the left Labbe vein with dilation of cortical veins and deep cerebral veins. He
      also suffered from pulmonary embolization and deep vein thrombosis in the lower
      extremities. Anticoagulant and thrombolytic agents were administered, then
      respiratory condition and hemiparesis were improved. However, his condition
      deteriolated 7 months after the initial attack. CT revealed huge subcortical
      hematoma in the same site. He underwent craniotomy and intracerebral hematoma was
      evacuated during treatment with vitamin K. His symptom gradually improved and he
      was discharged with moderate disability 2 months after operation. Dicision of
      surgical treatment is difficult because there is a risk of rebleeding due to
      thrombolytic therapy and progressive venous congestion. Since anticoagulant and
      thrombolytic therapy are inevitable, surgical indication for refractory
      intracerebral hemorrhage associated with cerebral venous thrombosis should be
      considered carefully.

PMID- 19175035
TI  - [High-flow arteriovenous fistula of the central nervous system associated with
      hereditary haemorrhagic telangiectasia].
AB  - The authors reported three cases of high flow arteriovenous fistula (AVF)
      associated with hereditary haemorrhagic telangiectasia (HHT). The first case was
      a 9-month-old boy who presented with subarachnoid hemorrhage (SAH). Digital
      subtraction angiography (DSA) revealed a perimedullary AVF at the cervical spine
      and the fistula was successfully interrupted by transarterial embolization with
      no additional neurological deficits. The second case was his mother, a 29-year
      old women. She also had history of epistaxis, so imaging screens of her central
      nervous system (CNS) were undertaken. MRI showed a giant intracerebral varix
      associated with a high-flow pial AVF. This patient was treated by surgery and
      postoperative CT angiography showed extinction of AVF completely. The third case
      was an 8-year-old girl with a family history of HHT. She presented with gradual
      progression of paraparesis, sensory disturbance in the bilateral lower
      extremities and bladder dysfunction. MRI disclosed a perimedullary AVF with a
      large varix at the L3/4 level. The AVF was successfully interrupted by
      transarterial embolization with platinum coils. Post-embolization DSA showed
      complete disappearance of the AVF. The existence of HHT must always be considered
      a possibility when AVF of the CNS is diagnosed.

PMID- 19175036
TI  - [Case of the jugular phlebectasia accompanied by the brachial plexopathy].
AB  - This article reports a case of a 59-year-old male who suffered from left brachial
      plexopathy occurring at night in bed. He had experienced multiple surgical
      courses of thyroid tumor resection including neck dissection and had presented
      left secondary jugular phlebectasia Jugular phlebectasia is mainly congenital and
      sometimes secondarily induced by compression, mechanical ventilation, trauma,
      thrombosis, etc. Brachial plexopathy is usually caused by neck and arm trauma,
      additionally caused by iatrogenic nerve and vessel injury. To our knowledge, this
      is the first report of brachial plexopathy accompanied by ipsilateral jugular
      phlebectasia. We hypothesized the etiology of this case through multimodal
      examinations and reviewed the literature about jugular phlebectasia and brachial
      plexopathy.

PMID- 19175037
TI  - [Operative neurosurgery: personal view and historical backgrounds. (5)
      Meningioma].
AB  - The author reports his experience of 410 surgeries of meningiomas on 365 cases
      during the last 13.5 years, including 51 surgeries on recurrent meningiomas and 8
      surgeries with the change of initial approach on the same meningiomas. In the
      surgical management of meningiomas, following comments are to be emphasized:
      Appropriate approach and interruption of blood supply are of cardinal importance
      in surgical management of meningiomas. For the latter purpose, preoperative
      embolization of feeding arteries is recommended especially in deep seated and
      large meningiomas more than 3 cm in diameter for carrying out their surgical
      extirpation fast and radically. Olfactory groove meningiomas, planum sphenoidal
      meningiomas, tuberculum sellae meningiomas and sphenoid ridge meningiomas are
      managed with pterional approach. The latter two meningiomas may necessitate
      selective extradural anterior clinoidectomy SEAC. For the management of large
      midline meningiomas, combination with interhemispheric approach is necessary to
      manage pial supply appropriately for the preservation of circulation of the
      anterior cerebral artery ACA. Extension of the former two meningiomas to the
      other side can be managed with falcal incision and/or drilling out of the crista
      galli without performing a bifrontal approach. Reduction of exophthalmos due to
      sphenoid ridge meningiomas infiltrating Periorbita and extraocular muscles is
      hardly to be expected even after subtotal removal and extensive decompression of
      the orbita at the superior and lateral walls in combination with SEAC. Accidental
      compromise of the lenticulostriate arteries arising from M1 portion embraced by
      tumor nodules should be managed with oxycellulose and fibrin glue at first
      without their bipolar coagulation, as resulting infarction in the territory
      causes persistent hemiparesis. Meningiomas in the cavernous sinus should be
      observed as long as possible in case of no growth, as they remain the same in
      their size and extension mostly for a long time. In case of growth, stereotactic
      radiosurgery is the first choice and at last would come surgical intervention at
      the cost of quality of life QOL. Appropriate approaches for meningiomas arising
      from the incisura tentorii would be either the amygdalohippocampectomy AHE
      approach namely transSylvian transsulcus circularis approach for their anterior
      localization or the supracerebellar transtentorial SCTT approach for the
      posterior localization in the sitting position. In the latter following
      structures are to be preserved with great care: A. parietooccipitalis, trochlear
      nerve, Vena Rosenthal and the superior cerebellar artery which could have
      considerable supply to the tumor. Meningiomas of the falcotentorial junction are
      managed also with this approach but may necessitate combination of the
      suboccipital transtentorial approach large upper clivus meningiomas can be
      removed more effectively by paramedian or lateral suboccipital craniotomy via
      SCTT approach in the sitting position rather than the subtemporal transpetrosal
      approach. Clean and wider operative fields in the former approach are emphasized.
      Special mention is made to transvertebralis (dural) ring approach TVRA for the
      foramen magnum or lower clivus meningiomas, in which the vertebral artery can be
      mobilized without performing more extensive far lateral approach. Difficulties of
      management of recurrent parasagittal meningiomas with the location corresponding
      to the gyrus paracentralis plus supplementary motor area are to be emphasized.
      Role of the venous sinus reconstruction is discussed. Difficulties of management
      of recurrent meningiomas represented by atypical or anaplastic meningiomas WHO
      grade II or III which can not be managed only by surgical removal is discussed by
      presenting some example cases. Biological activity of meningiomas in different
      location can be quite different in multiple recurrent meningiomas. Meningiomas
      intractable to irradiation and/or chemotherapy are another challenging topic,
      being beyond the scope of this paper.

PMID- 19175038
TI  - [Clinical standard of neurosurgical disorder. (2) Management of mild traumatic
      brain injury].

PMID- 19175039
TI  - Analysis of hMLH1 and hMSH2 expression in cisplatin-treated ovarian cancer
      patients.
AB  - BACKGROUND: Loss of DNA mismatch repair may result in resistance to platinum-
      based anticancer drugs. The hMLH1 and hMSH2 proteins play a critical role in the
      maintenance of genome integrity and are involved in resistance to platinum-based
      therapy in colorectal cancer, which is deficient in hMLH1 protein and endometrial
      cancer, as well as in hMSH2 protein. However, the predictive value of MLH1 and
      MSH2 expression in ovarian cancer cisplatin-resistance is still to be determined.
      OBJECTIVE: The aim of this study was to investigate the expression of hMLH1 and
      hMSH2 proteins in ovarian carcinoma specimens and to evaluate their prognostic
      significance by means of overall survival (OS) and progression-free survival
      rates (PSF). MATERIAL: Ovarian cancer tissues were obtained from 61 patients: 45
      platinum-sensitive and 16 platinum-resistant. hMLH1 and hMSH2 proteins expression
      was evaluated by immunohistochemistry, with the use of mouse monoclonal
      antibodies clone 14 for hMLH1 and clone FE11 for hMSH2. The log-rank test and
      Kaplan-Meier statistics were used to analyze the relationship between proteins
      expression and progression free survival, as well as the overall survival.
      RESULT: No significant correlation was found between hMLH1 and hMSH2 expression
      and overall survival and progression free survival in the group of patients
      sensitive and resistant to cisplatin. No significant difference was found in
      proteins expression intensity between the two compared groups of patients. Age of
      patients, type of cancer histology, FIGO staging, grading, clinical response and
      CA 125 did not reveal correlation with the expression of the analyzed proteins.
      CONCLUSION: The immunohistochemical expression of hMLH1 and hMSH2 proteins in
      ovarian cancer has no predictive value in resistance to cisplatin.

PMID- 19175040
TI  - Total Prolift System surgery for treatment posthysterectomy vaginal vault
      prolapse--do we treat both anatomy and function?
AB  - OBJECTIVES: To assess clinical efficacy of Total Prolift System surgery kit in
      the treatment of post hysterectomy vaginal vault prolapse. MATERIAL AND METHODS:
      Study group consisted of 27 women (mean age 60.3 +/- 10.3 years) who between
      February 2006 and September 2007 underwent vaginal cuff prolapse surgery with
      Total Prolift System. Nineteen patients had vaginal cuff prolapse POP-Q stage IV
      and 8 patients--POP-Q stage III with subjective feeling of prolapse. Seventeen
      patients were sexually active and among them twelve suffered from dyspareunia.
      Three patients had stress urinary incontinence and four OAB symptoms. Bladder
      emptying difficulty were present in seven and chronic constipation in four
      patients. RESULTS: Twenty one patients (77.8%) were available for follow up
      visits after 12 months. Only 3 out of 21 patients had recurrence of cystocoele
      but to a much less extent that (POP-Q stage II). This gives an efficacy of 85.7%
      in terms of anatomical restoration. SUI de novo occurred in two patients and OAB
      symptoms intensified in three women (in one case symptoms markedly decreased).
      Out of twenty one patients available on follow up visits thirteen (61.9%) were
      sexually active. Four women complained about dyspareunia, whereas women who
      complained for sexual dysfunction before operation were cured. Three patients
      were not completely satisfied with the effect of surgery due to occasional but
      severe pelvic pain causing difficulty with walking and moving. CONCLUSIONS:
      Gynecare Total Prolift System surgical kit enables simple and highly effective
      treatment of the vaginal vault prolapse, however there are some discrepancies
      between anatomical and functional results.

PMID- 19175041
TI  - [Women health behaviours regarding prevention and early detection of precancerous
      lesions and cervical carcinoma].
AB  - INTRODUCTION: In Poland, nearly 4000 women are diagnosed with it each year, with
      every second one of them dying. The primary prophylaxis includes: proper
      behaviour, avoidance of risk factors and vaccination against infections with of
      HPV. Secondary prophylaxis includes: screening and early detection and treatment
      of precancerous lesions. OBJECTIVES: The main objective of the following work was
      to assess women's health behaviours regarding prevention and early detection of
      precancerous lesions and cervical carcinoma. MATERIAL AND METHODS: 207 women at
      the age ranging from 21 to 81 (38,62 on average), were randomly chosen from women
      in the Przasnysz district. The women have been divided into two groups: those who
      were employed on various positions in hospital in Przasnysz (group A) and those
      who were in no way professionally involved in health service profession (group
      B). Research was performed using poll method and authorized questionnaire.
      RESULTS: Both groups did not differ from each other in socio-demographic sense.
      Women professionally connected with health service did not display a
      significantly better health behaviour. The connections between age, place of
      residence economic status, martial status, education level and healthy behavior
      have not been shown in this research. Few individual cases took part in screening
      and above 50% of women participated in educational programmes on prevention of
      cervical carcinoma development. CONCLUSION: To improve the situation in Poland,
      we should intensify educational activities and initiatives, especially with
      indication to health service employees as proponents of health behaviours.

PMID- 19175042
TI  - [The use of ThermoStapler--bipolar vessel sealing system in vaginal
      hysterectomy].
AB  - OBJECTIVES: The following study has been conducted to evaluate the efficacy of
      computer-controlled bipolar vessel sealing system (ThermoStapler, EMED), as an
      alternative to sutures, in order to achieve haemostasis during vaginal
      hysterectomy. MATERIAL AND METHODS: One hundred and twenty patients have
      undergone vaginal hysterectomy, half of them with the use of ThermoStapler vessel
      sealing system (n = 60) and the other half with standard surgical technique (n =
      60). Data compared in this retrospective study included the time of surgery,
      hemoglobin loss after the surgery, postoperative need for pain medication,
      duration of the hospital stay and intra/post-operative complications. RESULTS:
      The time of surgery proved to be shorter, although not significantly, in the
      group of vaginal hysterectomy with sutures when compared to the other group. The
      intra-operative blood loss, confirmed by pre- and postoperative hemoglobin
      measurements, appeared to be slightly lower in the ThermoStapler group. However,
      postoperative need for pain medication was significantly less frequent in the
      bipolar forceps group (P < 0.05). Complications and the duration of the hospital
      stay were similar in case of both groups. CONCLUSION: ThermoStapler bipolar
      vessel sealing system (EMED) proves to be a valuable alternative to traditional
      technique using surgical sutures, and an effective and safe method of achieving
      haemostasis during vaginal hysterectomy, resulting in significantly reduced need
      for pain medication during hospitalization.

PMID- 19175043
TI  - [Assessment of ultrasonography markers and CA125 usefulness in the diagnosis of
      ovarian cysts].
AB  - OBJECTIVES: The main aim of our study was to determine the features of the
      greatest importance in the prognosis of the functional nature of ovarian cysts,
      as well as the evaluation of the role of morphological index and CA 125 in the
      diagnosis of functional ovarian cysts. MATERIAL AND METHODS: 187 premenopausal
      women with ovarian tumor (between the ages of 13 and 52) were enrolled in the
      study. Each patient underwent transvaginal ultrasonography and the morphology of
      the tumor was assessed on the basis of morphological index. The level of CA 125
      was measured. The patients were divided into two groups: 1) patients with
      functional cyst, 2) patients with non-functional cyst. The study was performed
      between the years 2003-2006. RESULTS: Functional ovarian cysts in ultrasonography
      included: unilocular with smooth internal wall, anechoic, without solid elements
      and with a thin wall of the structure (< 3 mm). They were usually unilateral and
      ascites was rarely present. The morphological index (SM) achieved the highest
      accuracy (71.6%) at the cut-off level of > or = 5. The area under ROC curve for
      SM was 0.834. The level of CA 125 did not differ significantly between the
      analyzed groups. CONCLUSIONS: Tumors with 5 points or less in morphological index
      estimation may be safely observed during 2 or 3 menstruation cycles, as their
      spontaneous regression is anticipated. Assessment of CA 125 concentration is a
      test with low clinical usefulness and marginal statistical significance.

PMID- 19175044
TI  - [The risk of vertical transmission of HIV--the knowledge of gynaecologists and
      midwives].
AB  - AIM: The aim of the study was to assess the knowledge of gynaecologist and
      midwives concerning the risk of vertical transmission of HIV. MATERIAL AND
      METHODS: Anonymous questionnaires have been filled in by thirty
      gynaecologists/obstetricians and thirty midwives who work at hospital wards and
      ambulatory gynaecological surgeries in Bialystok. RESULTS: When asked about
      chances of an HIV positive woman, aware of her infection, giving birth to a
      healthy baby, only 3 doctors (10%) and 4 midwives (13.3%) provided the correct
      answer, namely that such chances exceed 98%. Natural delivery was considered
      safer for the baby by 12 doctors (36.7%) and 7 (23.3%) midwives. The others chose
      elective caesarean section as the preferred mode of delivery. Twenty-five doctors
      (13.3%) and 23 midwives (76.7%) were aware that HIVinfected women should not
      breast-feed. Four doctors (13.3%) and 6 midwives (20.0%) favoured breast-feeding.
      Only 7 doctors (23.3%) and 9 midwives (30.0%) knew that the diagnosis whether a
      child is infected or not, based on anti-HIV antibodies, is possible only after
      the child reaches the age of 18 months. CONCLUSIONS: Being aware of the
      limitations of our study, it is possible to formulate the following conclusion:
      Knowledge of gynaecologists/obstetricians and midwives about possibilities of HIV
      vertical transmission is insufficient for effective transmission prophylaxis.

PMID- 19175045
TI  - [Analysis of teenage pregnancy outcome and delivery between 2000 and 2006].
AB  - OBJECTIVES: The aim of our analysis was to retrospectively analyze the course of
      pregnancy and delivery in the group of Polish women, aged from 15 to 25. MATERIAL
      AND METHODS: We analyzed 345 woman, aged 15-25, treated in the KMMPiG ICZMP in
      Lodz between the years 2000 and 2006. The investigated patients were divided into
      two groups: 15-18-year-olds constituted the research group and 19-25-year-olds,
      that is the control group. Factors which have been taken into consideration
      included: pregnancy history, ultrasound examinations, delivery mode, birth weight
      and the APGAR score. RESULTS: 62.7% (n = 69) delivered naturally, 30.9% (n = 34)
      by caesarean section and 6.36% (n = 7) by forceps in the group of adolescents and
      67.6% (n = 159), 32.4% (n = 71) and 2% (n = 5) (p = 0.379; OR 1.27) in the
      control group. 25.5% (n = 26) of the adolescent women (< 37 week of gestation,
      WG) and 20.7% (n = 48) of the controls (p = 0.39; OR 1.31) had a pre-term
      delivery. There were 3.9% multiparas in the group of teenagers and 20.7% among
      adolescents (p = 0.001). Fetal malformations were diagnosed prenatally in 13.7%
      (n = 14) of newborns delivered by adolescents mothers and 11.6% (n = 27) in the
      control group (p = 0.591; OR 1.21). CONCLUSIONS: Despite the dangers connected
      with the young age of the mother, the results of this study allow us to state
      that teenage pregnancy usually has a correct course and does not differ
      significantly from the pregnancy of an adult woman.

PMID- 19175046
TI  - [Risk factors and frequency of occurrence of HPV DNA of high oncogenic types in
      paraepidermal epithelium cells of the uterine cervix, in the trophoblast, and in
      the peripheral blood of pregnant patients].
AB  - INTRODUCTION: During pregnancy viruses of high oncogenic potential--types 16, 18,
      31, 33, 35, which had so far remained in the state of chronic infection, undergo
      reactivation. Among the potential ways of HPV transmission to foetus, the direct
      perinatal infection is mentioned. In the antenatal period of pregnancy, a
      descending way of infection through blood is analyzed. OBJECTIVES: The purpose of
      this study is to evaluate the risk factors and frequency of occurrence of HPV DNA
      of high oncogenic types in paraepidermal epithelium cells of the uterine cervix,
      in the trophoblast, and in the peripheral blood of pregnant patients. MATERIAL
      AND METHODS: The research included 185 pregnant women hospitalized in the
      Delivery Room, of the Gynecological and Obstetric Clinic of the Poznan Medical
      University, in years 2005-2006. All patients who took part in the research had
      been interviewed prior to delivery with the help of a pre-designed questionnaire.
      Samples of cellular material from the cervix were collected before the delivery
      (185 specimens). 4-5 ml of peripheral blood (103 specimens) were collected as
      well. The collection of the cellular material was performed with the use of
      Cervex-Brush. Samples of tissue from placenta (138 specimens, including 5 pairs
      of twins) were collected after delivery. RESULTS: The research concludes, that
      incidental or chronic infection evoked by HPV HR presence in paraepidermal
      epithelium cells of the uterine cervix has been observed in nearly 30% of
      pregnant women. The presence of HPV HR DNA in the placenta cells of the HPV HR
      positive mothers applies to less than 6,5% of the researched women.
      Identification of the genetic material of Papillomavirus in peripheral blood of
      pregnant women indicates that this occurrence is incidental. The analysis of the
      risk factor of the development of HPV infection has exerted that the positive
      result of molecular tests on the presence of HPV HR DNA concerns the population
      of young women from 18 to 30 years of age. CONCLUSIONS: Incidental or persistent
      infection with highly oncogenic types of HPV present in cervix paraepidermal
      epithelium cells is observed in approximately 30% of pregnant women. The presence
      of DNA HPV HR in trophoblast cells of HPV HR positive mothers is diagnosed
      rarely, in less than 7% of pregnant women. Human Papilloma Virus is present in
      the peripheral blood of pregnant women sporadically. None of the currently known
      risk factors of HPV infection may be correlated with DNA HPV HR presence in
      pregnant women.

PMID- 19175047
TI  - [Progress in gynecological endocrinology].
AB  - The following paper attempted to present key articles on gynaecological
      endocrinology, published in the last three years. The aim of this study was not
      to describe and discuss complex and detailed endocrinological disorders. The
      author assumed readers possess appropriate knowledge about the presented issues.
      Thus, only the following topics have been presented: discoveries, new scientific
      conceptions and recently revised consensus and guidelines, which may be essential
      for practical application in gynaecological endocrinology. During the period of
      time under scrutiny, the pituitary-specific transcription factor-1 regulating the
      expression and differentiation of human growth hormone, prolactin and TSH, and
      the mechanism of the regulation of somatotrophs' apoptosis via Ret receptor have
      been discovered and defined. Furthermore, the fact that nuclear protein HMGA2
      induces formation of pituitary tumours has also been discovered. The paper
      emphasizes the practical value of research on side effects of the cabergoline.
      The consensus on diagnosing polycystic ovary syndrome (PCOS) has been discussed,
      with emphasis on the role of hyperandrogenism as a necessary criterion to make a
      diagnosis. PCOS treatment with metformin and treatment of infertility in case of
      PCOS guidelines have been presented as well. In the last part of the paper, the
      care for peri- and postmenopausal women, especially the problems of systemic and
      local hormonal therapy, has been described. Polish Gynaecological Society
      Standards are stated as well.

PMID- 19175049
TI  - [Efficacy of programs for rehabilitative correction of functional state of the
      body in patients with arterial hypertension].

PMID- 19175048
TI  - [Effectiveness of differential application of sodium chloride baths for the
      treatment of early forms of cerebrovascular diseases].
AB  - Treatment of patients at the early stages of cerebrovascular diseases with the
      use of sodium chloride baths resulted in the improvement of morphological and
      functional characteristics of brain vessels. Combination of sodium chloride baths
      with impulse currents and magnetic fields caused regression of neurologic and
      neuropsychotic disturbances in 80% of the patients. Beneficial therapeutic
      effects persisted especially long when the patients received the above treatment
      during 21-24 days.

PMID- 19175050
TI  - [Combined application of balneotherapy to the medical rehabilitation of patients
      with seronegative spondyloarthrites].
AB  - A rehabilitative complex combining radon baths and ultra-high frequency
      electromagnetic fields exerted a well-apparent beneficial effect on the clinical
      picture of articular and vertebral syndromes and greatly contributed to the
      correction of disturbances in the immune system of patients with seronegative
      spondyloarthritis. At the same time, combination of radon baths with low
      frequency ultrasound treatment and hydrocortisone ultraphonophoresis reduced
      clinical activity of the disease, improved the patients' immune status, and had
      more prominent general anti-inflammatory action than the same physical factors
      applied as monotherapy.

PMID- 19175051
TI  - [Optimization of vegetative regulation of mental and physical activities].
AB  - The objective of the study was to assess effects of combined treatment in young
      subjects with psychovegetative syndrome using physical factors (constant magnetic
      field and negatively polarized photoaeroions), soft tissue manual therapy, and
      graduated physical exercises for the correction of the mechanisms of vegetative
      regulations of mental and physical activities. The study has demonstrated the
      possibility to apply non-medicamentous treatment modalities for the improvement
      of intellectual work capacity by restoration of vegetative homeostasis,
      regression of pathological asymmetry of paired functioning of the heart meridian
      C (V), elimination of excessive asymmetry of interhemispheric blood flow, and
      reduction of the degree of impairment of paired functioning of the hemispheres.
      Increased productivity of physical activity was achieved by hemodynamic
      optimization of metabolic activity of the substrate responsible for the central
      regulation of motor activity.

PMID- 19175052
TI  - [Ultrasound in the treatment of patients with varicocele complicated by secretory
      form of pathospermia].
AB  - This paper presents a method for the ultrasound treatment of the skin of the male
      genital sphere and reports the results of therapy. The efficiency of this method
      for the management of varicocele was verified by its application in 64 patients
      with this pathology. Clinical efficacy of therapy was estimated at 56.4%.

PMID- 19175053
TI  - [Efficacy of balneoclimatic therapy in children with functional cardiomyopathy].

PMID- 19175054
TI  - [The role of reflexotherapy and physical training in the combined treatment and
      the prevention of paroxysmal form of idiopathic atrial fibrillation].

PMID- 19175055
TI  - [Effectiveness of laser puncture in elderly patients with bronchial asthma].

PMID- 19175056
TI  - [Application of massage of asymmetric chest zones in the combined treatment of
      patients with residual post-tuberculous changes in the lungs who underwent hip
      replacement in connection with tuberculous coxitis].

PMID- 19175057
TI  - [Chemotactic potential of phagocytes as a criterion for the efficacy of therapy
      in inflammatory diseases of the uterine appendages].

PMID- 19175058
TI  - [Integrated information resources--an indispensable condition for the efficacious
      management and successful functioning of the sanatorium-and-spa sector].

PMID- 19175060
TI  - Occlusion in patients with temporomandibular joint anterior disk displacement.
AB  - The aim of this study was to determine the correlation between the static and
      dynamic occlusal factors in patients with anterior disk displacement (DD) and to
      compare it with occlusion in asymptomatic individuals. The study included a group
      of 40 patients with DD (median age 35.5) and a control group of 25 students of
      dental medicine (median age 23.4). In all subjects, the position, i.e. DD was
      determined by magnetic resonance imaging of temporomandibular joints. The study
      was focused on data gathered by direct analysis of occlusion: relationship
      between the molars (Angle class), horizontal and vertical overlap, preservation
      of occlusal contacts between the molars (Eichner classification), difference
      between contact points in maximal intercuspidation and centric position, and
      contact points on the laterotrusive and mediotrusive side. There was a
      statistically significant difference in tooth contact in maximal intercuspidation
      and centric positions between patients and asymptomatic subjects (p < 0.0001).
      There was also a difference between occlusal contact points on the mediotrusive
      side (p < 0.05) since the hyperbalanced contacts were only determined in
      asymptomatic subjects. Study results support the fact that a number of occlusal
      factors are related to DD. The fact that hyperbalanced contacts were only
      determined in asymptomatic subjects suggests that their mutual etiopathogenetic
      correlation is not quite clear.

PMID- 19175059
TI  - Influence of Helicobacter pylori infection persistence on bcl-2 expression in
      gastric mucosa inflammatory cells.
AB  - Chronic Helicobacter (H.) pylori infection is an etiological factor related to
      gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT)
      lymphoma. The expression of bcl-2 protein significantly decreases as the grade of
      MALT lymphoma advances. The aim of this study was to evaluate bcl-2 expression in
      inflammatory cells in lamina propria in gastric biopsy samples collected from two
      groups of patients with chronic gastritis divided on the basis of the success or
      failure of H. pylori eradication. Sixty-five patients with chronic gastritis were
      divided into two groups of 45 and 20 patients according to their therapeutic
      response. The gastric mucosa samples were analyzed histologically in both groups
      of patients before and after standard therapy (for eradicated, after one
      therapeutic cycle; and for non-eradicated, after three therapeutic cycles) for H.
      pylori density, urease activity and bcl-2 expression. In the eradicated group of
      patients, H. pylori eradication was accompanied by significantly lower grades of
      bacterial colonization and lower urease activity in the corpus and antrum. Bcl-2
      expression in inflammatory cells showed no statistically significant changes in
      either patient group at either location. There was no between-group difference in
      bcl-2 expression either. In conclusion, persistent long-lasting H. pylori
      infection is associated with higher grades of bacterial colonization and higher
      urease activity but not with bcl-2 expression in inflammatory cells.

PMID- 19175061
TI  - Visual acuity and acute angle-closure glaucoma in Split-Dalmatia County.
AB  - The aim of this study was to determine the incidence of acute angle-closure
      glaucoma in Split-Dalmatia County and correlation between visual acuity and time
      (days) elapsed from the disease onset to hospital admission. Twenty-nine cases
      were retrospectively analyzed. There were 19 female patients aged 36-91 (median
      age 68) years and 10 male patients aged 35-88 (median age 70) years, with attacks
      of acute closure glaucoma treated at University Department of Ophthalmology,
      Split University Hospital Center from January 2002 until December 2005. Annual
      incidence was 1.6 cases per 100,000. The time elapsed from the disease onset to
      hospital admission was 1-21 (median 2) days. Visual acuity before and after
      treatment was reversely proportional to the number of days to hospital admission
      (d = -0.466; p = 0.011). Visual acuity was found to depend on age as well (z =
      1.999; p = 0.044). The best visual acuity was obtained in those cases that were
      admitted within two days (z = 2.014; p = 0.044). There was no significant sex
      difference in the incidence of angle-closure glaucoma (t = 0.389; p = 0.699). No
      statistically significant association was found between acute angle-closure
      glaucoma and seasonal variation (chi2 = 5; p = 0.167). In conclusion, earlier
      recognition of the symptoms of acute angle-closure glaucoma and initiation of
      treatment within two days of the disease onset were associated with better visual
      acuity.

PMID- 19175062
TI  - Sociodemographic and medical characteristics of involuntary psychiatric
      inpatients--retrospective study of five-year experience with Croatian Act on
      Mental Health.
AB  - The aim of this study was to analyze sociodemographic and medical characteristics
      of involuntary psychiatric inpatients treated during the five-year period of
      implementation of the Croatian Act on Mental Health. Data on involuntarily
      hospitalized patients according to the Croatian Act on Mental Health were singled
      out from the pool of inpatients treated at University Department of Psychiatry,
      Sestre milosrdnice University Hospital from January 1, 1998 till December 31,
      2002. Data were collected from medical records. Patients were diagnosed according
      to the International Classification of Diseases, 10th revision criteria. The
      prevalence of involuntary hospitalization was 2%, including a comparative number
      of male and female patients. Most patients had secondary school, were living
      alone, were unmarried, widowed or divorced, and did not work at the time of
      hospitalization; however, most patients had some kind of health insurance.
      Schizophrenia was the most common diagnosis in involuntary psychiatric
      inpatients. In conclusion, scientific evaluation of involuntary hospitalization
      poses a major problem because of the many different factors that can influence
      the prevalence of involuntary hospitalization. Some of this factors are type of
      institution (psychiatric hospital or psychiatry department at a general
      hospital), organization of psychiatric care in the region, psychiatric morbidity
      and dynamics of changes in psychiatric morbidity in a specific region, public
      opinion about people with mental disorders, legal provisions on this very
      sensitive topic, etc.

PMID- 19175063
TI  - Assessment of nurse attitudes on psychiatric patient compliance with
      pharmacotherapy.
AB  - The aim of the study was to assess the opinion of nurses employed at a psychiatry
      department about compliance with pharmacotherapy in patients they provide care
      for on a daily basis, i.e. assessment of the nurse's role in patient compliance
      with prescribed medication and how much the nurse can contribute to better
      patient compliance with pharmacotherapy. Thirty-nine nurses, i.e. 2/3 of nurses
      employed at University Department of Psychiatry, Sestre milosrdnice University
      Hospital, participated in the study Data were collected through a structured
      survey/questionnaire for nurses, which is used to assess the nurses' opinion of
      patient compliance with pharmacotherapy. Study results confirmed the belief that
      nurses recognize the importance of patient compliance in daily work and are aware
      that this compliance depends on the patient himself, his diagnosis, the medicine
      he receives, his family and medical professionals involved in his medical care.

PMID- 19175064
TI  - DNA ploidy in thymoma and associated multiple primary malignancies in the same
      patient.
AB  - Thymoma is an uncommon neoplasm derived from thymic epithelium. It is located in
      the anterosuperior mediastinum. Thymoma may be associated with different types of
      additional primary malignancies; however, colorectal adenocarcinoma and thyroid
      cancer appear to be most common. A case is presented of a 63-year-old woman with
      type A thymoma and two other primary carcinomas of the breast and colon that were
      previously diagnosed. The patient underwent surgery due to metastatic colon
      cancer of the lung and yet another primary tumor was found in the mediastinum,
      later diagnosed as thymoma. A normal diploid pattern was found in the samples of
      thymoma and colon carcinoma, whereas those of breast carcinoma and metastatic
      tumor of the lung showed aneuploidy. On the basis of previous studies and our
      case, it is concluded that the occurrence of extrathymic malignancies does not
      correlate with the biologic behavior and DNA ploidy of thymoma.

PMID- 19175065
TI  - Iridogoniodysgenesis syndrome: a case report.
AB  - A rare case is presented of iridogoniodysgenesis syndrome, an autosomal dominant
      inheritance disorder that includes abnormalities in the differentiation of the
      anterior segment structures and increased values of intraocular pressure, which
      at long run increases the risk of glaucomatous optic neuropathy. The syndrome is
      diagnosed when ocular changes are accompanied by extraocular structure anomalies
      such as maxillary hypoplasia, micro- and anodontia, redundant periumbilical skin,
      inguinal hernia and hypospadias (males). A 44-year-old male patient presented for
      treatment of retinal detachment on his left eye. Cataract surgery and pars plana
      vitrectomy with endolaser were done. Due to his vision loss, high intraocular
      pressure values bilaterally and positive family history of glaucoma, he was
      rehospitalized for complete glaucomatous diagnostic evaluation. The rare
      iridogoniodysgenesis syndrome and associated juvenile glaucoma were verified in
      the patient by positive family history of glaucoma, slit lamp iris hypoplasia and
      mild pupillary deformities, gonioscopic results of open angle with
      iridotrabecular synechiae and neovascularizations at the iris root and ciliary
      body, fundus examination showing optic disk changes with a cup to disk ratio of
      0.9 and 0.8 for the right and left eye, respectively, visual field dG2 program
      abnormalities such as absolute scotomata within 30 degrees on both eyes, and
      finally optical coherent tomography results of the cup to disk area ratio of 0.9
      and 0.8 for the right and left eye, respectively, with average thickness of the
      retinal nerve fiber layer of 51 mm and 72 mm for the right and left eye,
      respectively. Disease control was achieved with medicamentous therapy; however,
      continuous follow up of the patient is a priority to prevent the potential
      glaucomatous damage.

PMID- 19175066
TI  - Pancreatic endocrine tumor of uncertain behavior: a case report.
AB  - Pancreatic endocrine tumors are rare, and among them large non-functioning tumors
      of uncertain behavior are extremely infrequent. Non-functioning pancreatic
      endocrine tumors originate from the endocrine part of the pancreas but are not
      associated with a distinct hormonal syndrome. A rare case is presented of a 49
      year-old woman with a well-differentiated endocrine tumor of uncertain behavior
      that presented with intermittent pain in the epigastrium radiating to the right
      subcostal region. Computed tomography showed a well-defined and circumscribed
      solid mass in the pancreas head. The pancreatic mass was surgically removed and
      submitted for histopathologic analysis. Microscopically, the tumor had relatively
      uniform cells with oval nuclei that coated trabecular and pseudoglandular
      structures, which also showed 1 mitosis per 10 VVP and proliferation activity
      measured with Ki67 of less than 2%. A focus of intravascular invasion was seen on
      one slide. Immunohistochemical analyses for NSE, chromogranin and synapthophysin
      were positive, which along with its size (over 2 cm in diameter) and reported
      angioinvasion indicated the diagnosis of pancreatic endocrine tumor of uncertain
      behavior. Although mostly considered as malignant, large non-functioning
      pancreatic endocrine tumors can sometimes express benign or uncertain behavior;
      therefore, a large number of factors should always be considered when determining
      the biological nature of these tumors.

PMID- 19175067
TI  - Why does the patient with Graves' disease remain euthyroid/mildly hyperthyroid
      following total thyroidectomy--the role of thyrotropin receptor antibodies (TRAb)
      and vestigial remnants of the thyroglossal tract.
AB  - A young female patient suffering from Graves' disease is presented, who raised
      some diagnostic and therapeutic dilemmas after being diagnosed with subclinical
      hyperthyroidism following total thyroidectomy. This 20-year-old female patient,
      carrier of HLA B8 DR3 genes, was referred to our hospital for total thyroidectomy
      after developing severe leukopenia on both methimazole and propylthiouracil
      therapy. A high postoperative titer of thyrotropin receptor antibodies and
      positive scintigraphy finding of the pyramidal lobe and remnant thyroid tissue in
      the left thyroid lobe led to the administration of radioiodine. Despite further
      enlargement of the remnant thyroid tissue on post-radioiodine scintiscanning, the
      patient is currently euthyroid, with normal thyroid-stimulating hormone levels;
      however, her long-term prognosis remains uncertain.

PMID- 19175068
TI  - Intravitreal bevacizumab for neovascular glaucoma.
AB  - The aim of the study was to assess short-term efficacy of intravitreal
      bevacizumab in a series of patients with neovascular glaucoma. Eleven patients
      with neovascular glaucoma and symptomatic elevation of intraocular pressure were
      treated with 1.25 mg/0.1 mL of bevacizumab. In three patients, intravitreal
      bevacizumab was administered preoperatively, one day before pars plana
      vitrectomy. Additional therapy was only performed if topical medication failed to
      result in satisfactory control of intraocular pressure. Patients were followed-up
      for a minimum of 8 weeks. In all study patients, intravitreal application of
      bevacizumab resulted in marked regression of iris neovascularization within the
      first three postoperative days. Appropriate control of intraocular pressure was
      achieved in seven patients, whereas four patients required additional therapy for
      intraocular pressure regulation. No side effects of intravitreal bevacizumab were
      recorded. Thus, intravitreal bevacizumab seems to be a potent adjunct in the
      management of neovascular glaucoma. Additional studies of bevacizumab long-term
      safety and efficacy are warranted.

PMID- 19175069
TI  - Recommendations for neuropathic pain treatment.
AB  - Damage to the somatosensory nervous system poses a risk for the development of
      neuropathic pain. Such an injury to the nervous system results in a series of
      neurobiological events resulting in sensitization of both the peripheral and
      central nervous system. The symptoms include continuous background pain (often
      burning or crushing in nature) and spasmodic pain (shooting, stabbing or
      "electrical"). The diagnosis of neuropathic pain is based primarily on the
      history and physical examination finding. Although monotherapy is the ideal
      approach, rational polypharmacy is often pragmatically used. Several classes of
      drugs are moderately effective, but complete or near-complete relief is unlikely.
      Antidepressants and anticonvulsants are most commonly used. Opioid analgesics can
      provide some relief but are less effective than for nociceptive pain; adverse
      effects may prevent adequate analgesia. Topical drugs and a lidocaine-containing
      patch may be effective for peripheral syndromes. Sympathetic blockade is usually
      ineffective except for some patients with complex regional pain syndrome.

PMID- 19175070
TI  - [Histological detection of dried tiny thyroid tissue in health foods].
AB  - Two patients were diagnosed as having hyperthyroidism, and both had taken the
      same health food. We compared three kinds of histological methods to detect
      thyroid gland in this health food. The first method used cytology; the second
      applied the cell-block method; and the last is a modification of the cell
      particle (CPCB) method proposed by Ushijima. It is the third method that achieved
      superior results, and this enabled the morphological detection of thyroid gland.
      Certain kinds of health foods contain dried thyroid as a "slimming supplement",
      and intake of these products may damage health. Histological techniques are
      effective for detecting the existence of dried thyroid gland. A health food is
      very different from clinical specimen; therefore, we have to devise appropriate
      skills for examining it. Such examinations will be important in the future,
      because it is expected that the risks of damaging health by consuming certain
      kinds of health food will increase.

PMID- 19175071
TI  - [Immunoresponse to SS-A 52-kDa and 60-kDa proteins in mothers of infants with
      neonatal lupus erythematosus].
AB  - BACKGROUND: Neonatal lupus erythematosus (NLE) is a rare disorder caused by the
      transplacental passage of maternal autoantibodies and manifests with
      characteristic skin eruption and/or congenital heart block. Anti-SS-A 52-kDa and
      60-kDa antibodies are important serology markers for the diagnosis of NLE.
      However, women who have these antibodies do not always give birth to children
      with NLE. Therefore, we investigated the avidity (quality of the antibody) using
      urea derivative. METHODS: The sera of 54 women and 19 umbilical cord blood
      specimens were measured using a commercial ELISA kit (MESACUP 52K SS-A/Ro and 60K
      SS-A/Ro, MBL). Avidity index (AI) was obtained using a reagent prepared according
      to the method described in the European patent EP 0875761 as well as in the
      Japanese patent application No. 10-121896. RESULTS: Mothers with infants
      demonstrating atrioventricular block (AB) showed higher antibody indices for 52
      kDa protein than mothers of infants without AB (p=0.0145). Mothers with cutaneous
      NLE had higher antibody indices for 60-kDa protein than mothers without cutaneous
      NLE (p=0.0058). Mothers had higher antibody indices and AIs than fetuses. There
      was a positive correlation between the antibody index and AI. The level of AI was
      increased in patients demonstrating low platelet counts in umbilical cord blood,
      but high antibody indices did not always increase in relation to the low platelet
      counts in umbilical cord blood. CONCLUSIONS: Mothers with high antibody indices
      do not always give birth to children with NLE, even if the AIs of the mother are
      high. The fetus side, that is, the factor on the antigen side would be more
      important. However, we conjecture that anti-60-kDa antibody influences the
      development of cutaneous NLE, and that anti-52-kDa antibody influences the
      development of NLE with AB. The high AI may be related to more severe symptoms of
      NLE.

PMID- 19175072
TI  - [Expression analysis of microRNAs in erythropoiesis].
AB  - microRNAs (miRNAs) are non-coding RNAs, and are negatively regulating the gene
      functions through translational repression or digesting mRNAs by targeting 3'-UTR
      in messenger RNAs (mRNAs). To clarify roles of miRNAs in normal and pathological
      erythropoiesis, we analyzed the expression of miR-451, miR-155, miR-221 in normal
      human erythroid colony forming cells (ECFCs) and circulating red blood cells
      using quantitative real-time polymerase chain reaction. Remarkable down
      regulation of miR-155 (about 200-fold) and up-regulation of miR-451 (270-fold)
      were observed during 12 days of ECFC cultures. miR-221 was down-regulated
      moderately (20-fold). Since mature erythroid cells expressed miR-451 at high
      levels, we analyzed the content of miR-451 in fractionated peripheral blood cells
      obtained from normal subjects (n= 3), and found that the expression level of miR
      451 in red blood cells was about 10(4)-fold more than in granulocytes and
      mononuclear cells. Analysis of packed red cells from normal subjects (n=3) and
      patients with hematological disorders (n=16), showed that there was no
      significant difference of the expression levels of miR-451 between normal and
      patients. In conclusion, expression profiles of miR-155 and miR-451 are stage
      specific during normal erythropoiesis in which miR-155 is down-regulated and miR
      451 is up-regulated. A high expression of miR-451 is specific to red blood cells
      among circulating blood cells. These observations suggest that an analysis of
      microRNAs is a new relevant approach to understand underlying mechanisms of
      hematological disorders.

PMID- 19175073
TI  - [Usefulness of the formula for predicting creatinine clearance from serum
      cystatin C].
AB  - Estimation of Glomerular filtration rate (GFR) is crucial for the detection of
      renal insufficiency. In clinical practice, GFR is generally estimated from Ccr by
      some prediction formulas including the serum creatinine concentration and some
      variables: age, sex, body size. It has been suggested that serum cystatin C is
      less influenced by sex, body size, muscular mass or inflammation. In several
      studies, serum cystatin C performed better than serum creatinine did as a marker
      to detect GFR reduction. We developed the formula for predicting creatinine
      clearance (Ccr) from serum cystatin C, serum creatinine and serum beta 2
      microgroburin by multiple regression analysis. In this study, we analysed 24-hour
      Ccr and variables (sex, age and BMI) in 82 subjects with renal diseases to
      develop suitable formulas. Our serum cystatin C formula is as follows: Ccr
      (ml/min/1.73m2) = (12.14-0.03 x age-1.72 x serum cystatin C) 2. Correlation
      between measured 24-hour Ccr and predicted Ccr by our serum cystatin C formula
      was higher (r=0.852) than our serum creatinine formula (r=0.755), serum beta 2
      microgroburin formula (r=0.793), Cockcroft-Gault formula (r=0.836) and Horio
      formula (r=0.825). Accuracy within 15% was higher (39.0%) than other formulas
      (25.6-30.5%). Our formula using serum cystatin C for predicting Ccr is a useful
      and precise marker for Ccr than other commonly used formulas using serum
      creatinine.

PMID- 19175074
TI  - [Verification of exhaled air temperature and heat flux in respiratory diseases as
      useful biomarker].
AB  - Asthma, chronic obstructive pulmonary disease, and diffuse panbronchiolitis are
      syndromes associated with chronic airway inflammation. In the conventional
      definition of inflammation, local pyrexia at the site of inflammation should be
      observed. However, there are very few reports that have evaluated the "heat" in
      inflammatory respiratory diseases. We considered that the evaluation of allergic
      airway inflammation such as asthma might be possible by measuring the exhaled air
      temperature, and devised an original device that stabilizes the flow rate, which
      is a very important factor for the direct measurement of heat. Moreover, an
      expiratory heat flux meter, which can detect a change in air temperature more
      precisely and immediately, was also incorporated into our original device. As a
      result, we succeeded in the measurement and evaluation of the heat flux and air
      temperature in healthy subjects and asthmatic patients, and, further, the air
      temperature was straightforwardly evaluated by a portable spirometer including a
      temperature sensor. These findings suggest that the heat flux and temperature of
      exhaled air can be used to objectively monitor airway inflammation noninvasively,
      and assist in the diagnosis/monitoring of inflammatory respiratory diseases,
      including asthma.

PMID- 19175075
TI  - [Cross-talk between arteriosclerotic diseases and allergic inflammation].
AB  - Arteriosclerosis and allergy are increasingly common diseases. The pathogeneses
      are both based on changes in lifestyle and chronic inflammation. Herein we
      discuss cross talk between the two seemingly unrelated diseases, focusing on
      obesity and various related molecules, including adipokines, peroxisome
      proliferator-activated receptors (PPARs), C reactive protein (CRP), and soluble
      adhesion molecules.

PMID- 19175076
TI  - [Current diagnosis of secondary hypertension associated with the
      endocrinopathies].
AB  - Secondary hypertension is an elevated blood pressure resulting from an underlying
      and identifiable cause. Only about 5 to 10 percent of hypertension cases are
      thought to result from secondary causes. Primary aldosteronism (PA) and Cushing's
      syndrome are typical endocrinopathies developing this type of hypertension.
      Herein, the updated diagnostic guidelines for these diseases and some problems
      arising from them are reviewed. Hypertensive patients diagnosed with PA have been
      increasing significantly based on screening tests using the aldosterone-renin
      ratio (ARR). We usually suspect hypertensive patients with an ARR of 20 or more
      as having PA, and plan confirmatory tests, such as captopril, furosemide-upright,
      saline-loading, and rapid ACTH tests. Although the diagnosis of PA is not
      complicated endocrinologically, it is sometimes difficult to decide on the
      laterality of the adrenal lesion. Aldosterone-producing adenoma (APA) is
      sometimes too small to detect and indistinguishable from non-functional nodules
      on CT. Therefore, adrenal venous sampling (AVS) is reliable for the
      lateralization of PA. Cushing's syndrome is involved in refractory hypertension.
      Because hypertension associated with this syndrome could be improved markedly
      through treatment of the primary lesion, it is important to diagnose it at an
      early stage. To detect this syndrome simply and correctly, the measurement of
      salivary cortisol (sF), as a substitute for plasma cortisol (pF), has recently
      been paid attention. In our studies, it was demonstrated that midnight sF was
      closely correlated with midnight pF. This suggests that midnight sF can be useful
      in the diagnosis of Cushing's syndrome. Herein, the sensitivity and specificity
      of this examination in our cases are discussed.

PMID- 19175077
TI  - [Development of three-dimensional analysis of current density distribution by 64
      ch magentocardiography and clinical application].
AB  - Magnetocardiography (MCG) using a SQUID sensor is characterized by three
      dimensional cardiac electrical phenomena from magnetic fields, because it is hard
      to be affected by organ constitution of lungs and torso configuration. We have
      developed three-dimensional (3D) electric current density distribution analysis
      by a spatial filter method. At this symposium, we report clinical utility of 64
      channel (64-ch) MCG. Subjects consisted of 20 normal volunteers, 10 cases with
      old myocardial infarction, 13 cases with atrial fibrillation (AFIB) who received
      surgical pulmonary (PV) isolation, and representative case with fetus premature
      ventricular complex (PVC). We recorded 10-min MCG data of magnetic field
      composition (a Bz ingredient) which was perpendicular to body surface in a
      magnetism shield, using 64-ch SQUID sensors (17.5 x 17.5 cm) built-in in MCG
      instrumentation(sampling; 500ms, total frequency characteristic; 0.1-200 Hz). We
      conducted 3D heart outline from electric current density calculated by magnetic
      field distribution. We also generated 3D functional images of the RT (activation
      recovery time) dispersion and spatial spectral distribution of a fibrillation
      wave. Increased fluctuation on RT dispersion map corresponded with space location
      of myocardial infarction. The mean frequency of 3D spectral map in persistent
      AFIB showed a higher value than that with restored a sinus rhythm (7.7 +/- 0.5 Hz
      vs. 6.5 +/- 0.7 Hz). We also demonstrated a fetus PVC. We concluded that 64-ch
      MCG can evaluate 3D spatial location of myocardial injury, 3D spectral map and
      characteristic frequency, and fetus arrhythmia. In future, further technical
      development in the fields of MCG measurement would be necessary for avoiding the
      used of unshielded room or liquid He.

PMID- 19175078
TI  - [Laboratory medicine in the post-genome era: experiences in Chiba University
      Hospital].
AB  - Since the completion of the human genome project, there is growing interest in
      the clinical application of genome sciences. For this purpose, particular
      attention toward identifying at-risk individuals and understanding the
      complexities of the testing process are essential. In this article, I describe
      the importance of clinical genetics and genetic counseling, and explain how and
      why the division of laboratory medicine is involved in these tasks in Chiba
      University Hospital. Our genetic counseling team consists of a clinical
      laboratory physician qualified as a clinical geneticist, medical technologist
      qualified as a genetic counselor, clinical psychologists, and a medical social
      worker. We treat more than 100 cases including late-onset, incurable neurological
      diseases, hereditary tumors, prenatal diagnosis, and chromosomal abnormalities.
      The sequencing of the human genome has paved the way for comprehensive
      transcriptome and proteome analyses. Since the detailed understanding of
      biological processes, both in healthy and pathological states, requires the
      direct study of relevant proteins, proteomics bridges the gap between the
      information coded in the genome sequence and cellular behavior. Therefore,
      proteomics is among the most promising technologies for the development of novel
      diagnostic tools. Recent advances in sophisticated technologies in proteomics
      should identify promising ways to discover novel markers in various fields of
      clinical medicine. In this presentation, I will give a definition of the
      proteome, and outline the basic methodologies for proteome analyses. I will also
      present our experiences in identifying novel biomarker candidates in
      hepatobiliary diseases, and discuss future perspectives of clinical proteomics in
      laboratory medicine.

PMID- 19175079
TI  - Point/counterpoint. There is currently enough evidence and technology available
      to warrant taking immediate steps to reduce exposure of consumers to cell-phone
      related electromagnetic radiation.

PMID- 19175080
TI  - Direct-conversion flat-panel imager with avalanche gain: feasibility
      investigation for HARP-AMFPI.
AB  - The authors are investigating the concept of a direct-conversion flat-panel
      imager with avalanche gain for low-dose x-ray imaging. It consists of an
      amorphous selenium (a-Se) photoconductor partitioned into a thick drift region
      for x-ray-to-charge conversion and a relatively thin region called high-gain
      avalanche rushing photoconductor (HARP) in which the charge undergoes avalanche
      multiplication. An active matrix of thin film transistors is used to read out the
      electronic image. The authors call the proposed imager HARP active matrix flat
      panel imager (HARP-AMFPI). The key advantages of HARP-AMFPI are its high spatial
      resolution, owing to the direct-conversion a-Se layer, and its programmable
      avalanche gain, which can be enabled during low dose fluoroscopy to overcome
      electronic noise and disabled during high dose radiography to prevent saturation
      of the detector elements. This article investigates key design considerations for
      HARP-AMFPI. The effects of electronic noise on the imaging performance of HARP
      AMFPI were modeled theoretically and system parameters were optimized for
      radiography and fluoroscopy. The following imager properties were determined as a
      function of avalanche gain: (1) the spatial frequency dependent detective quantum
      efficiency; (2) fill factor; (3) dynamic range and linearity; and (4) gain
      nonuniformities resulting from electric field strength nonuniformities. The
      authors results showed that avalanche gains of 5 and 20 enable x-ray quantum
      noise limited performance throughout the entire exposure range in radiography and
      fluoroscopy, respectively. It was shown that HARP-AMFPI can provide the required
      gain while maintaining a 100% effective fill factor and a piecewise dynamic range
      over five orders of magnitude (10(-7)-10(-2) R/frame). The authors have also
      shown that imaging performance is not significantly affected by the following:
      electric field strength nonuniformities, avalanche noise for x-ray energies above
      1 keV and direct interaction of x rays in the gain region. Thus, HARP-AMFPI is a
      promising flat-panel imager structure that enables high-resolution fully quantum
      noise limited x-ray imaging over a wide exposure range.

PMID- 19175082
TI  - Planning and delivery of intensity-modulated radiation therapy.
AB  - Intensity modulated radiation therapy (IMRT) is an advanced form of external beam
      radiation therapy. IMRT offers an additional dimension of freedom as compared
      with field shaping in three-dimensional conformal radiation therapy because the
      radiation intensities within a radiation field can be varied according to the
      preferences of locations within a given beam direction from which the radiation
      is directed to the tumor. This added freedom allows the treatment planning system
      to better shape the radiation doses to conform to the target volume while sparing
      surrounding normal structures. The resulting dosimetric advantage has shown to
      translate into clinical advantages of improving local and regional tumor control.
      It also offers a valuable mechanism for dose escalation to tumors while
      simultaneously reducing radiation toxicities to the surrounding normal tissue and
      sensitive structures. In less than a decade, IMRT has become common practice in
      radiation oncology. Looking forward, the authors wonder if IMRT has matured to
      such a point that the room for further improvement has diminished and so it is
      pertinent to ask what the future will hold for IMRT. This article attempts to
      look from the perspective of the current state of the technology to predict the
      immediate trends and the future directions. This article will (1) review the
      clinical experience of IMRT; (2) review what we learned in IMRT planning; (3)
      review different treatment delivery techniques; and finally, (4) predict the
      areas of advancements in the years to come.

PMID- 19175081
TI  - Three-dimensional linear system analysis for breast tomosynthesis.
AB  - The optimization of digital breast tomosynthesis (DBT) geometry and
      reconstruction is crucial for the clinical translation of this exciting new
      imaging technique. In the present work, the authors developed a three-dimensional
      (3D) cascaded linear system model for DBT to investigate the effects of detector
      performance, imaging geometry, and image reconstruction algorithm on the
      reconstructed image quality. The characteristics of a prototype DBT system
      equipped with an amorphous selenium flat-panel detector and filtered
      backprojection reconstruction were used as an example in the implementation of
      the linear system model. The propagation of signal and noise in the frequency
      domain was divided into six cascaded stages incorporating the detector
      performance, imaging geometry, and reconstruction filters. The reconstructed
      tomosynthesis imaging quality was characterized by spatial frequency dependent
      presampling modulation transfer function (MTF), noise power spectrum (NPS), and
      detective quantum efficiency (DQE) in 3D. The results showed that both MTF and
      NPS were affected by the angular range of the tomosynthesis scan and the
      reconstruction filters. For image planes parallel to the detector (in-plane), MTF
      at low frequencies was improved with increase in angular range. The shape of the
      NPS was affected by the reconstruction filters. Noise aliasing in 3D could be
      introduced by insufficient voxel sampling, especially in the z (slice-thickness)
      direction where the sampling distance (slice thickness) could be more than ten
      times that for in-plane images. Aliasing increases the noise at high frequencies,
      which causes degradation in DQE. Application of a reconstruction filter that
      limits the frequency components beyond the Nyquist frequency in the z direction,
      referred to as the slice thickness filter, eliminates noise aliasing and improves
      3D DQE. The focal spot blur, which arises from continuous tube travel during
      tomosynthesis acquisition, could degrade DQE significantly because it introduces
      correlation in signal only, not NPS.

PMID- 19175083
TI  - Image artifacts in digital breast tomosynthesis: investigation of the effects of
      system geometry and reconstruction parameters using a linear system approach.
AB  - Digital breast tomosynthesis (DBT) is a three-dimensional (3D) x-ray imaging
      modality that reconstructs image slices parallel to the detector plane. Image
      acquisition is performed using a limited angular range (less than 50 degrees) and
      a limited number of projection views (less than 50 views). Due to incomplete data
      sampling, image artifacts are unavoidable in DBT. In this preliminary study, the
      image artifacts in DBT were investigated systematically using a linear system
      approximation. A cascaded linear system model of DBT was developed to calculate
      the 3D presampling modulation transfer function (MTF) with different image
      acquisition geometries and reconstruction filters using a filtered backprojection
      (FBP) algorithm. A thin, slanted tungsten (W) wire was used to measure the
      presampling MTF of the DBT system in the cross-sectional plane defined by the
      thickness (z-) and tube travel (x-) directions. The measurement was in excellent
      agreement with the calculation using the model. A small steel bead was used to
      calculate the artifact spread function (ASF) of the DBT system. The ASF was
      correlated with the convolution of the two-dimensional (2D) point spread function
      (PSF) of the system and the object function of the bead. The results showed that
      the cascaded linear system model can be used to predict the magnitude of image
      artifacts of small, high-contrast objects with different image acquisition
      geometry and reconstruction filters.

PMID- 19175085
TI  - On the use of HDR 60Co source with the MammoSite radiation therapy system.
AB  - This work summarizes Monte Carlo results in order to evaluate the potential of
      using HDR 60Co sources in accelerated partial breast irradiation (APBI) with the
      MammoSite applicator. Simulations have been performed using the MCNP5 Monte Carlo
      Code, in simple geometries comprised of two concentric spheres; the internal
      consisting of selected concentrations, C, of a radiographic contrast solution in
      water (Omnipaque 300) to simulate the MammoSite balloon and the external
      consisting of water to simulate surrounding tissue. The magnitude of the
      perturbation of delivered dose due to the radiographic contrast medium used in
      the MammoSite applicator is calculated. At the very close vicinity of the balloon
      surface, a dose build-up region is observed, which leads to a dose overestimation
      by the treatment planning system (TPS) which depends on Omnipaque 300 solution
      concentration (and is in order of 2.3%, 3.0%, and 4.5%, respectively, at 1 mm
      away from the balloon - water interface, for C=10%, 15%, and 20%). However, dose
      overestimation by the TPS is minimal for points lying at the prescription
      distance (d=1 cm) or beyond, for all simulated concentrations and radii of
      MammoSite balloon. An analytical estimation of the integral dose outside the CTV
      in the simple geometries simulated shows that dose to the breast for MammoSite
      applications is expected to be comparable using HDR 60Co and 192Ir sources, and
      higher than that for 169Yb. The higher enegies of 60Co sources result to
      approximately twice radiation protection requirements as compared to 169Ir
      sources. However, they allow for more accurate dosimetry calculation with
      currently used treatment planning algorithms for 60Co sources, compared to 169Ir.

PMID- 19175084
TI  - Development of a quantitative method for analysis of breast density based on
      three-dimensional breast MRI.
AB  - Breast density has been established as an independent risk factor associated with
      the development of breast cancer. It is known that an increase of mammographic
      density is associated with an increased cancer risk. Since a mammogram is a
      projection image, different body position, level of compression, and the x-ray
      intensity may lead to a large variability in the density measurement. Breast MRI
      provides strong soft tissue contrast between fibroglandular and fatty tissues,
      and three-dimensional coverage of the entire breast, thus making it suitable for
      density analysis. To develop the MRI-based method, the first task is to achieve
      consistency in segmentation of the breast region from the body. The method
      included an initial segmentation based on body landmarks of each individual
      woman, followed by fuzzy C-mean (FCM) classification to exclude air and lung
      tissue, B-spline curve fitting to exclude chest wall muscle, and dynamic
      searching to exclude skin. Then, within the segmented breast, the adaptive FCM
      was used for simultaneous bias field correction and fibroglandular tissue
      segmentation. The intraoperator and interoperator reproducibility was evaluated
      using 11 selected cases covering a broad spectrum of breast densities with
      different parenchymal patterns. The average standard deviation for breast volume
      and percent density measurements was in the range of 3%-4% among three trials of
      one operator or among three different operators. The body position dependence was
      also investigated by performing scans of two healthy volunteers, each at five
      different positions, and found the variation in the range of 3%-4%. These initial
      results suggest that the technique based on three-dimensional MRI can achieve
      reasonable consistency to be applied in longitudinal follow-up studies to detect
      small changes. It may also provide a reliable method for evaluating the change of
      breast density for risk management of women, or for evaluating the benefits/risks
      when considering hormonal replacement therapy or chemoprevention.

PMID- 19175086
TI  - A simplified method of four-dimensional dose accumulation using the mean patient
      density representation.
AB  - The purpose of this work was to demonstrate, both in phantom and patient, the
      feasibility of using an average 4DCT image set (AVG-CT) for 4D cumulative dose
      estimation. A series of 4DCT numerical phantoms and corresponding AVG-CTs were
      generated. For full 4D dose summation, static dose was calculated on each phase
      and cumulative dose was determined by combining each phase's static dose
      distribution with known tumor displacement. The AVG-CT cumulative dose was
      calculated similarly, although the same AVG-CT static dose distribution was used
      for all phases (i.e., tumor displacements). Four lung cancer cases were also
      evaluated for stereotactic body radiotherapy and conformal treatments; however,
      deformable image registration of the 4DCTs was used to generate the displacement
      vector fields (DVFs) describing patient-specific motion. Dose discrepancy between
      full 4D summation and AVG-CT approach was calculated and compared. For all
      phantoms, AVG-CT approximation yielded slightly higher cumulative doses compared
      to full 4D summation, with dose discrepancy increasing with increased tumor
      excursion. In vivo, using the AVG-CT coupled with deformable registration yielded
      clinically insignificant differences for all GTV parameters including the
      minimum, mean, maximum, dose to 99% of target, and dose to 1% of target.
      Furthermore, analysis of the spinal cord, esophagus, and heart revealed
      negligible differences in major dosimetric indices and dose coverage between the
      two dose calculation techniques. Simplifying 4D dose accumulation via the AVG-CT,
      while fully accounting for tumor deformation due to respiratory motion, has been
      validated, thereby, introducing the potential to streamline the use of 4D dose
      calculations in clinical practice, particularly for adaptive planning purposes.

PMID- 19175087
TI  - Mean glandular dose estimation using MCNPX for a digital breast tomosynthesis
      system with tungsten/aluminum and tungsten/aluminum+silver x-ray anode-filter
      combinations.
AB  - Breast cancer screening with x-ray mammography, using one or two projection
      images of the breast, is an indispensible tool in the early detection of breast
      cancer in women. Digital breast tomosynthesis (DBT) is a 3D imaging technique
      that promises higher sensitivity and specificity in breast cancer screening at a
      similar radiation dose to conventional two-view screening mammography. In DBT a
      3D volume is reconstructed with anisotropic voxels from a limited number of x-ray
      projection images acquired over a limited angle. Although the benefit of early
      cancer detection through screening mammography outweighs the potential risks
      associated with radiation, the radiation dosage to women in terms of mean
      glandular dose (MGD) is carefully monitored. This work studies the MGD arising
      from a prototype DBT system under various parameters. Two anode/filter
      combinations (W/Al and W/Al+Ag) were investigated; the tube potential ranges from
      20 to 50 kVp; and the breast size varied between 4 and 10 cm chest wall-to-nipple
      distance and between 3 and 7 cm compressed breast thickness. The dosimetric
      effect of breast positioning with respect to the imaging detector was also
      reviewed. It was found that the position of the breast can affect the MGD by as
      much as 5% to 13% depending on the breast size.

PMID- 19175088
TI  - Texture classification-based segmentation of lung affected by interstitial
      pneumonia in high-resolution CT.
AB  - Accurate and automated lung field (LF) segmentation in high-resolution computed
      tomography (HRCT) is highly challenged by the presence of pathologies affecting
      lung borders, also affecting the performance of computer-aided diagnosis (CAD)
      schemes. In this work, a two-dimensional LF segmentation algorithm adapted to
      interstitial pneumonia (IP) patterns is presented. The algorithm employs k-means
      clustering followed by a filling operation to obtain an initial LF order
      estimate. The final LF border is obtained by an iterative support vector machine
      neighborhood labeling of border pixels based on gray level and wavelet
      coefficient statistics features. A second feature set based on gray level
      averaging and gradient features was also investigated to evaluate its effect on
      segmentation performance of the proposed method. The proposed method is evaluated
      on a dataset of 22 HRCT cases spanning a range of IP patterns such as ground
      glass, reticular, and honeycombing. The accuracy of the method is assessed using
      area overlap and shape differentiation metrics (d(mean), d(rms), and d(max)), by
      comparing automatically derived lung borders to manually traced ones, and further
      compared to a gray level thresholding-based (GLT-based) method. Accuracy of the
      methods evaluated is also compared to interobserver variability. The proposed
      method incorporating gray level and wavelet coefficient statistics demonstrated
      the highest segmentation accuracy, averaged over left and right LFs
      (overlap=0.954, d(mean)=1.080 mm, d(rms)=1.407 mm, and d(max)=4.944 mm), which is
      statistically significant (two-tailed student's t test for paired data, p<0.0083)
      with respect to all metrics considered as compared to the proposed method
      incorporating gray level averaging and gradient features (overlap=0.918,
      d(mean)=2.354 mm, d(rms)=3.711 mm, and d(max)=14.412 mm) and the GLT-based method
      (overlap=0.897, d(mean)=3.618 mm, d(rms)=5.007 mm, and d(max)=16.893 mm). The
      performance of the three segmentation methods, although decreased as IP pattern
      severity level (mild, moderate, and severe) was increased, did not demonstrate
      statistically significant difference (two-tailed student's t test for unpaired
      data, p>0.0167 for all metrics considered). Finally, the accuracy of the proposed
      method, based on gray level and wavelet coefficient statistics ranges within
      interobserver variability. The proposed segmentation method could be used as an
      initial stage of a CAD scheme for IP patterns.

PMID- 19175089
TI  - Phantom evaluation of a commercially available three modality image guided
      radiation therapy system.
AB  - The authors describe a detailed evaluation of the capabilities of imaging and
      image registration systems available with Varian linear accelerators for image
      guided radiation therapy (IGRT). Specifically, they present modulation transfer
      function curves for megavoltage planar, kilovoltage (kV) planar, and cone beam
      computed tomography imaging systems and compare these with conventional computed
      tomography. While kV planar imaging displayed the highest spatial resolution, all
      IGRT imaging techniques were assessed as adequate for their intended purpose.
      They have also characterized the image registration software available for use in
      conjunction with these imaging systems through a comprehensive phantom study
      involving translations in three orthogonal directions. All combinations of
      imaging systems and image registration software were found to be accurate,
      although the planar kV imaging system with automatic registration was generally
      superior, with both accuracy and precision of the order of 1 mm, under the
      conditions tested. Based on their phantom study, the attainable accuracy for
      rigid body translations using any of the features available with Varian equipment
      will more likely be limited by the resolution of the couch readouts than by
      inherent limitations in the imaging systems and image registration software.
      Overall, the accuracy and precision of currently available IGRT technology exceed
      published experience with the accuracy and precision of contouring for planning.

PMID- 19175090
TI  - A correction-based dose calculation algorithm for kilovoltage x rays.
AB  - Frequent and repeated imaging procedures such as those performed in image-guided
      radiotherapy (IGRT) programs may add significant dose to radiosensitive organs of
      radiotherapy patients. It has been shown that kV-CBCT results in doses to bone
      that are up to a factor of 3-4 higher than those in surrounding soft tissue.
      Imaging guidance procedures are necessary due to their potential benefits, but
      the additional incremental dose per treatment fraction may exceed an individual
      organ tolerance. Hence it is important to manage and account for this additional
      dose from imaging for radiotherapy patients. Currently available model-based dose
      calculation methods in radiation treatment planning (RTP) systems are not
      suitable for low-energy x rays, and new and fast calculation algorithms are
      needed for a RTP system for kilovoltage dose computations. This study presents a
      new dose calculation algorithm, referred to as the medium-dependent-correction
      (MDC) algorithm, for accurate patient dose calculation resulting from kilovoltage
      x rays. The accuracy of the new algorithm is validated against Monte Carlo
      calculations. The new algorithm overcomes the deficiency of existing density
      correction based algorithms in dose calculations for inhomogeneous media,
      especially for CT-based human volumetric images used in radiotherapy treatment
      planning.

PMID- 19175091
TI  - Noise power properties of a cone-beam CT system for breast cancer detection.
AB  - The noise power properties of a cone-beam computed tomography (CT) system
      dedicated for breast cancer detection were investigated. Uniform polyethylene
      cylinders of various diameters were scanned under different system acquisition
      conditions. Noise power spectra were calculated from difference data generated by
      subtraction between two identical scans. Multidimensional noise power spectra
      (NPS) were used as the metric to evaluate the noise properties of the breast CT
      (bCT) under different system acquisition and reconstruction conditions. A
      comprehensive investigation of the noise properties was performed in regard to
      system acquisition parameters including kVp, mA, number of cone-beam projection
      images used, cone angle, and object size. The influence on reconstruction
      parameters including interpolation method, reconstruction filter, field of view,
      matrix size, and slice thickness were also studied. Under certain conditions, the
      zero-dimensional NPS (image variance) was used as a quantitative index to compare
      the influence from different scan parameters, especially the radiation dose. If
      the total scan dose is changed by linearly changing the total number of
      projection images while the dose per frame is kept constant, the noise power has
      a linear relationship with the reciprocal of the total dose. If the total scan
      dose is changed by linearly changing the dose per frame while the total number of
      projection images is kept constant, the noise power has a quadratic relationship
      with the reciprocal of the total dose. With the same amount of total dose, using
      fewer projection images results in lower image noise power in the CT image.
      Quantitative results from this noise power analysis provide guidance for the bCT
      system operation, optimization, and data reconstruction.

PMID- 19175092
TI  - In vivo quantification of contrast agent concentration using the induced magnetic
      field for time-resolved arterial input function measurement with MRI.
AB  - For pharmacokinetic modeling of tissue physiology, there is great interest in
      measuring the arterial input function (AIF) from dynamic contrast-enhanced (DCE)
      magnetic resonance imaging (MRI) using paramagnetic contrast agents. Due to
      relaxation effects, the measured signal is a nonlinear function of the injected
      contrast agent concentration and depends on sequence parameters, system
      calibration, and time-of-flight effects, making it difficult to accurately
      measure the AIF during the first pass. Paramagnetic contrast agents also affect
      susceptibility and modify the magnetic field in proportion to their
      concentration. This information is contained in the MR signal phase which is
      discarded in a typical image reconstruction. However, quantifying AIF through
      contrast agent susceptibility induced phase changes is made difficult by the fact
      that the induced magnetic field is nonlocal and depends upon the contrast agent
      spatial distribution and thus on organ and vessel shapes. In this article, the
      contrast agent susceptibility was quantified through inversion of magnetic field
      shifts using a piece-wise constant model. Its feasibility is demonstrated by a
      determination of the AIF from the susceptibility-induced field changes of an
      intravenous bolus. After in vitro validation, a time-resolved two-dimensional
      (2D) gradient echo scan, triggered to diastole, was performed in vivo on the
      aortic arch during a bolus injection of 0.1 mmol/kg Gd-DTPA. An approximate
      geometrical model of the aortic arch constructed from the magnitude images was
      used to calculate the spatial variation of the field associated with the bolus.
      In 14 subjects, Gd concentration curves were measured dynamically (one
      measurement per heart beat) and indirectly validated by independent 2D cine phase
      contrast flow rate measurements. Flow rate measurements using indicator
      conservation with this novel quantitative susceptibility imaging technique were
      found to be in good agreement with those obtained from the cine phase contrast
      measurements in all subjects. Contrary to techniques that rely on intensity, the
      accuracy of this signal phase based method is insensitive to factors influencing
      signal intensity such as flip angle, coil sensitivity, relaxation changes, and
      time-of-flight effects extending the range of pulse sequences and contrast doses
      for which quantitative DCE-MRI can be applied.

PMID- 19175093
TI  - Automated regional registration and characterization of corresponding
      microcalcification clusters on temporal pairs of mammograms for interval change
      analysis.
AB  - A computerized regional registration and characterization system for analysis of
      microcalcification clusters on serial mammograms is being developed in our
      laboratory. The system consists of two stages. In the first stage, based on the
      location of a detected cluster on the current mammogram, a regional registration
      procedure identifies the local area on the prior that may contain the
      corresponding cluster. A search program is used to detect cluster candidates
      within the local area. The detected cluster on the current image is then paired
      with the cluster candidates on the prior image to form true (TP-TP) or false (TP
      FP) pairs. Automatically extracted features were used in a newly designed
      correspondence classifier to reduce the number of false pairs. In the second
      stage, a temporal classifier, based on both current and prior information, is
      used if a cluster has been detected on the prior image, and a current classifier,
      based on current information alone, is used if no prior cluster has been
      detected. The data set used in this study consisted of 261 serial pairs
      containing biopsy-proven calcification clusters. An MQSA radiologist identified
      the corresponding clusters on the mammograms. On the priors, the radiologist
      rated the subtlety of 30 clusters (out of the 261 clusters) as 9 or 10 on a scale
      of 1 (very obvious) to 10 (very subtle). Leave-one-case-out resampling was used
      for feature selection and classification in both the correspondence and
      malignant/benign classification schemes. The search program detected 91.2%
      (238/261) of the clusters on the priors with an average of 0.42 FPs/image. The
      correspondence classifier identified 86.6% (226/261) of the TP-TP pairs with 20
      false matches (0.08 FPs/image) relative to the entire set of 261 image pairs. In
      the malignant/benign classification stage the temporal classifier achieved a test
      A(z) of 0.81 for the 246 pairs which contained a detection on the prior. In
      addition, a classifier was designed by using the clusters on the current
      mammograms only. It achieved a test A(z) of 0.72 in classifying the clusters as
      malignant and benign. The difference between the performance of the temporal
      classifier and the current classifier was statistically significant (p=0.0014).
      Our interval change analysis system can detect the corresponding cluster on the
      prior mammogram with high sensitivity, and classify them with a satisfactory
      accuracy.

PMID- 19175094
TI  - Lung tumor tracking in fluoroscopic video based on optical flow.
AB  - Respiratory gating and tumor tracking for dynamic multileaf collimator delivery
      require accurate and real-time localization of the lung tumor position during
      treatment. Deriving tumor position from external surrogates such as abdominal
      surface motion may have large uncertainties due to the intra- and interfraction
      variations of the correlation between the external surrogates and internal tumor
      motion. Implanted fiducial markers can be used to track tumors fluoroscopically
      in real time with sufficient accuracy. However, it may not be a practical
      procedure when implanting fiducials bronchoscopically. In this work, a method is
      presented to track the lung tumor mass or relevant anatomic features projected in
      fluoroscopic images without implanted fiducial markers based on an optical flow
      algorithm. The algorithm generates the centroid position of the tracked target
      and ignores shape changes of the tumor mass shadow. The tracking starts with a
      segmented tumor projection in an initial image frame. Then, the optical flow
      between this and all incoming frames acquired during treatment delivery is
      computed as initial estimations of tumor centroid displacements. The tumor
      contour in the initial frame is transferred to the incoming frames based on the
      average of the motion vectors, and its positions in the incoming frames are
      determined by fine-tuning the contour positions using a template matching
      algorithm with a small search range. The tracking results were validated by
      comparing with clinician determined contours on each frame. The position
      difference in 95% of the frames was found to be less than 1.4 pixels
      (approximately 0.7 mm) in the best case and 2.8 pixels (approximately 1.4 mm) in
      the worst case for the five patients studied.

PMID- 19175095
TI  - Determination of absorbed dose in water at the reference point d(r0, theta0) for
      an 192Ir HDR brachytherapy source using a Fricke system.
AB  - A ring-shaped Fricke device was developed to measure the absolute dose on the
      transverse bisector of a 192Ir high dose rate (HDR) source at 1 cm from its
      center in water, D(r0, theta0). It consists of a polymethylmethacrylate (PMMA)
      rod (axial axis) with a cylindrical cavity at its center to insert the 192Ir
      radioactive source. A ring cavity around the source with 1.5 mm thickness and 5
      mm height is centered at 1 cm from the central axis of the source. This ring
      cavity is etched in a disk shaped base with 2.65 cm diameter and 0.90 cm
      thickness. The cavity has a wall around it 0.25 cm thick. This ring is filled
      with Fricke solution, sealed, and the whole assembly is immersed in water during
      irradiations. The device takes advantage of the cylindrical geometry to measure
      D(r0, theta0). Irradiations were performed with a Nucletron microselectron HDR
      unit loaded with an 192Ir Alpha Omega radioactive source. A Spectronic 1001
      spectrophotometer was used to measure the optical absorbance using a 1 mL quartz
      cuvette with 1.00 cm light pathlength. The PENELOPE Monte Carlo code (MC) was
      utilized to simulate the Fricke device and the 192Ir Alpha Omega source in detail
      to calculate the perturbation introduced by the PMMA material. A NIST traceable
      calibrated well type ionization chamber was used to determine the air-kerma
      strength, and a published dose-rate constant was used to determine the dose rate
      at the reference point. The time to deliver 30.00 Gy to the reference point was
      calculated. This absorbed dose was then compared to the absorbed dose measured by
      the Fricke solution. Based on MC simulation, the PMMA of the Fricke device
      increases the D(r0, theta0) by 2.0%. Applying the corresponding correction
      factor, the D(r0, theta0) value assessed with the Fricke device agrees within
      2.0% with the expected value with a total combined uncertainty of 3.43% (k=1).
      The Fricke device provides a promising method towards calibration of
      brachytherapy radiation sources in terms of D(r0, theta0) and audit HDR source
      calibrations.

PMID- 19175096
TI  - Monte Carlo evaluation of a treatment planning system for helical tomotherapy in
      an anthropomorphic heterogeneous phantom and for clinical treatment plans.
AB  - Helical tomotherapy is an increasingly common form of intensity modulated
      radiation therapy that allows for image guided adaptive radiotherapy. Its
      treatment planning system (TPS) uses a convolution superposition algorithm for
      dose distribution calculations. The accuracy of this algorithm in the presence of
      heterogeneities was evaluated against Monte Carlo (MC) calculations and
      measurements. This work performed BEAMnrc-and DOSXYZnrc-based MC dose
      calculations of tomotherapy deliveries to a CIRS anthropomorphic heterogeneous
      phantom with typical clinical inverse planning and delivery settings. Point
      measurements with A1SL ion chambers and relative measurements with Kodak EDR2
      film were carried out in the phantom. The experimental results were used to
      evaluate both the TPS and MC dose calculations. Furthermore, the dose
      distribution for a clinical head-and-neck cancer plan was calculated on the TPS
      and MC systems. The results support this MC system as a viable option for the
      accurate simulation of the tomotherapy process in the presence of heterogeneities
      where direct measurement may not be practical. Ion chamber measurements in the
      CIRS phantom suggested the TPS has an average relative difference of 2.3%, with
      the largest difference being -4.1% in one of the organs at risk. The MC system
      accurately predicted the dose to these measurement points within statistical
      uncertainty. The film measurements in the CIRS phantom demonstrated 90.7% (of
      pixels) agreed with the MC system using a +/-3%/3 mm acceptance criteria, where
      only 50.3% agreed with the TPS. In the clinical head-and-neck cancer plan
      evaluation where MC served as a reference against which to compare the TPS
      result, an average of 92.7% of the voxels within volumes of interest passed a
      3%/3 mm criteria. The PTV54 showed the worst agreement with 85.4% of the volume
      passing the 3% /3 mm criteria. In general, the +/-3%/3 mm criterion was found to
      be a challenge for the TPS in the presence of lung inhomogeneity.

PMID- 19175097
TI  - Automatic segmentation of the facial nerve and chorda tympani in CT images using
      spatially dependent feature values.
AB  - In cochlear implant surgery, an electrode array is permanently implanted in the
      cochlea to stimulate the auditory nerve and allow deaf people to hear. A
      minimally invasive surgical technique has recently been proposed-percutaneous
      cochlear access-in which a single hole is drilled from the skull surface to the
      cochlea. For the method to be feasible, a safe and effective drilling trajectory
      must be determined using a preoperative CT. Segmentation of the structures of the
      ear would improve trajectory planning safety and efficiency and enable the
      possibility of automated planning. Two important structures of the ear, the
      facial nerve and the chorda tympani, are difficult to segment with traditional
      methods because of their size (diameters as small as 1.0 and 0.3 mm,
      respectively), the lack of contrast with adjacent structures, and large
      interpatient variations. A multipart, model-based segmentation algorithm is
      presented in this article that accomplishes automatic segmentation of the facial
      nerve and chorda tympani. Segmentation results are presented for ten test ears
      and are compared to manually segmented surfaces. The results show that the
      maximum error in structure wall localization is approximately 2 voxels for the
      facial nerve and the chorda, demonstrating that the method the authors propose is
      robust and accurate.

PMID- 19175098
TI  - In vivo accuracy assessment of a needle-based navigation system for CT-guided
      radiofrequency ablation of the liver.
AB  - Computed tomography (CT)-guided percutaneous radiofrequency ablation (RFA) has
      become a commonly used procedure in the treatment of liver tumors. One of the
      main challenges related to the method is the exact placement of the instrument
      within the lesion. To address this issue, a system was developed for computer
      assisted needle placement which uses a set of fiducial needles to compensate for
      organ motion in real time. The purpose of this study was to assess the accuracy
      of the system in vivo. Two medical experts with experience in CT-guided
      interventions and two nonexperts used the navigation system to perform 32 needle
      insertions into contrasted agar nodules injected into the livers of two
      ventilated swine. Skin-to-target path planning and real-time needle guidance were
      based on preinterventional 1 mm CT data slices. The lesions were hit in 97% of
      all trials with a mean user error of 2.4 +/- 2.1 mm, a mean target registration
      error (TRE) of 2.1 +/- 1.1 mm, and a mean overall targeting error of 3.7 +/- 2.3
      mm. The nonexperts achieved significantly better results than the experts with an
      overall error of 2.8 +/- 1.4 mm (n=16) compared to 4.5 +/- 2.7 mm (n=16). The
      mean time for performing four needle insertions based on one preinterventional
      planning CT was 57 +/- 19 min with a mean setup time of 27 min, which includes
      the steps fiducial insertion (24 +/- 15 min), planning CT acquisition (1 +/- 0
      min), and registration (2 +/- 1 min). The mean time for path planning and
      targeting was 5 +/- 4 and 2 +/- 1 min, respectively. Apart from the fiducial
      insertion step, experts and nonexperts performed comparably fast. It is concluded
      that the system allows for accurate needle placement into hepatic tumors based on
      one planning CT and could thus enable considerable improvement to the clinical
      treatment standard for RFA procedures and other CT-guided interventions in the
      liver. To support clinical application of the method, optimization of individual
      system modules to reduce intervention time is proposed.

PMID- 19175099
TI  - Mechanically assisted 3D ultrasound guided prostate biopsy system.
AB  - There are currently limitations associated with the prostate biopsy procedure,
      which is the most commonly used method for a definitive diagnosis of prostate
      cancer. With the use of two-dimensional (2D) transrectal ultrasound (TRUS) for
      needle-guidance in this procedure, the physician has restricted anatomical
      reference points for guiding the needle to target sites. Further, any motion of
      the physician's hand during the procedure may cause the prostate to move or
      deform to a prohibitive extent. These variations make it difficult to establish a
      consistent reference frame for guiding a needle. We have developed a 3D
      navigation system for prostate biopsy, which addresses these shortcomings. This
      system is composed of a 3D US imaging subsystem and a passive mechanical arm to
      minimize prostate motion. To validate our prototype, a series of experiments were
      performed on prostate phantoms. The 3D scan of the string phantom produced
      minimal geometric distortions, and the geometric error of the 3D imaging
      subsystem was 0.37 mm. The accuracy of 3D prostate segmentation was determined by
      comparing the known volume in a certified phantom to a reconstructed volume
      generated by our system and was shown to estimate the volume with less then 5%
      error. Biopsy needle guidance accuracy tests in agar prostate phantoms showed
      that the mean error was 2.1 mm and the 3D location of the biopsy core was
      recorded with a mean error of 1.8 mm. In this paper, we describe the mechanical
      design and validation of the prototype system using an in vitro prostate phantom.
      Preliminary results from an ongoing clinical trial show that prostate motion is
      small with an in-plane displacement of less than 1 mm during the biopsy
      procedure.

PMID- 19175101
TI  - An international dosimetry exchange for BNCT part II: computational dosimetry
      normalizations.
AB  - The meaningful sharing and combining of clinical results from different centers
      in the world performing boron neutron capture therapy (BNCT) requires improved
      precision in dose specification between programs. To this end absorbed dose
      normalizations were performed for the European clinical centers at the Joint
      Research Centre of the European Commission, Petten (The Netherlands), Nuclear
      Research Institute, Rez (Czech Republic), VTT, Espoo (Finland), and Studsvik,
      Nykoping (Sweden). Each European group prepared a treatment plan calculation that
      was bench-marked against Massachusetts Institute of Technology (MIT) dosimetry
      performed in a large, water-filled phantom to uniformly evaluate dose
      specifications with an estimated precision of +/-2%-3%. These normalizations were
      compared with those derived from an earlier exchange between Brookhaven National
      Laboratory (BNL) and MIT in the USA. Neglecting the uncertainties related to
      biological weighting factors, large variations between calculated and measured
      dose are apparent that depend upon the 10B uptake in tissue. Assuming a boron
      concentration of 15 microg g(-1) in normal tissue, differences in the evaluated
      maximum dose to brain for the same nominal specification of 10 Gy(w) at the
      different facilities range between 7.6 and 13.2 Gy(w) in the trials using
      boronophenylalanine (BPA) as the boron delivery compound and between 8.9 and 11.1
      Gy(w) in the two boron sulfhydryl (BSH) studies. Most notably, the value for the
      same specified dose of 10 Gy(w) determined at the different participating centers
      using BPA is significantly higher than at BNL by 32% (MIT), 43% (VTT), 49% (JRC),
      and 74% (Studsvik). Conversion of dose specification is now possible between all
      active participants and should be incorporated into future multi-center patient
      analyses.

PMID- 19175100
TI  - Quantification of breast density with dual energy mammography: a simulation
      study.
AB  - Breast density, the percentage of glandular breast tissue, has been identified as
      an important yet underutilized risk factor in the development of breast cancer. A
      quantitative method to measure breast density with dual energy imaging was
      investigated using a computer simulation model. Two configurations to measure
      breast density were evaluated: the usage of monoenergetic beams and an ideal
      detector, and the usage of polyenergetic beams with spectra from a tungsten anode
      x-ray tube with a detector modeled after a digital mammography system. The
      simulation model calculated the mean glandular dose necessary to quantify the
      variability of breast density to within 1/3%. The breast was modeled as a
      semicircle 10 cm in radius with equal homogenous thicknesses of adipose and
      glandular tissues. Breast thicknesses were considered in the range of 2-10 cm and
      energies in the range of 10-150 keV for the two monoenergetic beams, and 20-150
      kVp for spectra with a tungsten anode x-ray tube. For a 4.2 cm breast thickness,
      the required mean glandular doses were 0.183 microGy for two monoenergetic beams
      at 19 and 71 keV, and 9.85 microGy for two polyenergetic spectra from a tungsten
      anode at 32 and 96 kVp with beam filtrations of 50 microm Rh and 300 microm Cu
      for the low and high energy beams, respectively. The results suggest that for
      either configuration, breast density can be precisely measured with dual energy
      imaging requiring only a small amount of additional dose to the breast. The
      possibility of using a standard screening mammogram as the low energy image is
      also discussed.

PMID- 19175102
TI  - A genetic algorithm for variable selection in logistic regression analysis of
      radiotherapy treatment outcomes.
AB  - A given outcome of radiotherapy treatment can be modeled by analyzing its
      correlation with a combination of dosimetric, physiological, biological, and
      clinical factors, through a logistic regression fit of a large patient
      population. The quality of the fit is measured by the combination of the
      predictive power of this particular set of factors and the statistical
      significance of the individual factors in the model. We developed a genetic
      algorithm (GA), in which a small sample of all the possible combinations of
      variables are fitted to the patient data. New models are derived from the best
      models, through crossover and mutation operations, and are in turn fitted. The
      process is repeated until the sample converges to the combination of factors that
      best predicts the outcome. The GA was tested on a data set that investigated the
      incidence of lung injury in NSCLC patients treated with 3DCRT. The GA identified
      a model with two variables as the best predictor of radiation pneumonitis: the
      V30 (p=0.048) and the ongoing use of tobacco at the time of referral (p=0.074).
      This two-variable model was confirmed as the best model by analyzing all possible
      combinations of factors. In conclusion, genetic algorithms provide a reliable and
      fast way to select significant factors in logistic regression analysis of large
      clinical studies.

PMID- 19175104
TI  - 3D dynamic model of healthy and pathologic arteries for ultrasound technique
      evaluation.
AB  - A 3D model reproducing the biomechanical behavior of human blood vessels is
      presented. The model, based on a multilayer geometry composed of right
      generalized cylinders, enables the representation of different vessel
      morphologies, including bifurcations, either healthy or affected by stenoses.
      Using a finite element approach, blood flow is simulated by considering a dynamic
      displacement of the scatterers (erythrocytes), while arterial pulsation due to
      the hydraulic pressure is taken into account through a fluid-structure
      interaction based on a wall model. Each region is acoustically characterized
      using FIELD II software, which produces the radio frequency echo signals
      corresponding to echographic scans. Three acoustic physiological phantoms of
      carotid arteries surrounded by elastic tissue are presented to illustrate the
      model's capability. The first corresponds to a healthy blood vessel, the second
      includes a 50% stenosis, and the third represents a carotid bifurcation. Examples
      of M mode, B mode and color Doppler images derived from these phantoms are shown.
      Two examples of M-mode image segmentation and the identification of the
      atherosclerotic plaque boundaries on Doppler color images are reported. The model
      could be used as a tool for the preliminary evaluation of ultrasound signal
      processing and visualization techniques.

PMID- 19175103
TI  - Technical note: Heterogeneity dose calculation accuracy in IMRT: study of five
      commercial treatment planning systems using an anthropomorphic thorax phantom.
AB  - The purpose of this study was to determine the accuracy of five commonly used
      intensity-modulated radiation therapy (IMRT) treatment planning systems (TPSs), 3
      using convolution superposition algorithms or the analytical anisotropic
      algorithm (CSA/AAAs) and 2 using pencil beam algorithms (PBAs), in calculating
      the absorbed dose within a low-density, heterogeneous region when compared with
      measurements made in an anthropomorphic thorax phantom. The dose predicted in the
      target center met the test criteria (5% of the dose normalization point or 3 mm
      distance to agreement) for all TPSs tested; however, at the tumor-lung interface
      and at the peripheral lung in the vicinity of the tumor, the CSA/AAAs performed
      better than the PBAs (85% and 50%, respectively, of pixels meeting the 5%/3-mm
      test criteria), and thus should be used to determine dose in heterogeneous
      regions.

PMID- 19175105
TI  - Determination of the prescription dose for biradionuclide permanent prostate
      brachytherapy.
AB  - A model based on the linear quadratic model that has been corrected for
      repopulation, sublethal cell damage repair, and RBE effect has been used to
      determine the prescription dose for prostate permanent brachytherapy using seeds
      loaded with a mixture of 103Pd and 125I or a mixture of 103Pd and 131Cs. The
      prescription dose was determined by comparing the tumor cell survival fractions
      between the considered biradionuclide seed implant and one monoradionuclide seed
      implant chosen from 103Pd, 125I, and 131Cs. Prostate edema is included in the
      model. The influence of the value of the radiobiological parameters and RBE were
      also investigated. Two mixtures of radionuclides were considered: 103Pd0.75
      125I0.25 and 103Pd0.25-131Cs0.75, where the subscripts indicate the fractions of
      total initial internal activity in the biradionuclide seed. These fractions were
      selected in order to obtain a dose distribution that lies between that of 103Pd
      and 125I/131Cs. As expected, the computed prescription dose values are dependent
      on the model parameters (edema half-life and magnitude, radiobiogical parameters,
      and RBE). The radionuclide used as a benchmark also has a strong impact on the
      derived prescribed dose. The large uncertainties in the radiobiological
      parameters and RBE values produce big errors in the computed prescribed dose.
      Averaged over the range of all the parameters and depending on the radionuclide
      used as a benchmark (in subscript), the derived prescription dose for the first
      mixture (PdI) would be: D(PdI)(Pd)=142(+15)(-16) Gy and D(PdI)(I)=142(+6)(-8) Gy;
      and D(PdCs)(Pd)=128(+13)(-13) Gy and D(PdCs)(Cs)=115(+6)(-7) Gy for the PdCs
      mixture. The uncertainties could be reduced if the radiobiological parameters and
      RBE value were known more accurately. However, as edema characteristics are
      patient dependent and can be obtained only after the treatment, an unpredictable
      error is unavoidable.

PMID- 19175106
TI  - Absolute and relative dose measurements with Gafchromic EBT film for high energy
      electron beams with different doses per pulse.
AB  - The authors have evaluated the accuracy, in absolute and relative dose
      measurements, of the Gafchromic EBT film in pulsed high-energy electron beams.
      Typically, the electron beams used in radiotherapy have a dose-per-pulse value of
      less than 0.1 mGy/pulse. However, very high dose-per-pulse electron beams are
      employed in certain linear accelerators dedicated to intraoperatory radiation
      therapy (IORT). In this study, the absorbed dose measurements with Gafchromic EBT
      in both low (less than 0.3 mGy per pulse) and high (30 and 70 mGy per pulse) dose
      per-pulse electron beams were compared with ferrous sulfate chemical Fricke
      dosimetry (operated by the Italian Primary Standard Dosimetry Laboratory), a
      method independent of the dose per pulse. A summary of Gafchromic EBT in relative
      and absolute beam output determination is reported. This study demonstrates the
      independence of Gafchromic EBT absorption as a function of dose per pulse at
      different dose levels. A good agreement (within 3%) was found with Fricke
      dosimeters for plane-base IORT applicators. Comparison with a diode detector is
      presented for relative dose measurements, showing acceptable agreement both in
      the steep dose falloff zone and in the homogeneous dose region. This work also
      provides experimental values for recombination correction factor (Ksat) of a Roos
      (plane parallel) ionization chamber calculated on the basis of theoretical models
      for charge recombination.

PMID- 19175107
TI  - AAPM Task Group 128: quality assurance tests for prostate brachytherapy
      ultrasound systems.
AB  - While ultrasound guided prostate brachytherapy has gained wide acceptance as a
      primary treatment tool for prostate cancer, quality assurance of the ultrasound
      guidance system has received very little attention. Task Group 128 of the
      American Association of Physicists in Medicine was created to address quality
      assurance requirements specific to transrectal ultrasound used for guidance of
      prostate brachytherapy. Accurate imaging guidance and dosimetry calculation
      depend upon the quality and accuracy of the ultrasound image. Therefore, a robust
      quality assurance program for the ultrasound system is essential. A brief review
      of prostate brachytherapy and ultrasound physics is provided, followed by a
      recommendation for elements to be included in a comprehensive test phantom.
      Specific test recommendations are presented, covering grayscale visibility, depth
      of penetration, axial and lateral resolution, distance measurement, area
      measurement, volume measurement, needle template/electronic grid alignment, and
      geometric consistency with the treatment planning computer.

PMID- 19175109
TI  - Analysis of image quality for real-time target tracking using simultaneous kV-MV
      imaging.
AB  - Real-time tracking can provide high accuracy localization for a moving target and
      minimize the effect of motion. Simultaneous kV-MV imaging has been proposed as a
      real-time tracking technique by utilizing the existing kV on-board imager (OBI)
      and the MV electronic portal device (EPID) mounted on the linear accelerator. The
      orthogonal pair of kV-MV images acquired simultaneously can provide 3-D
      localization in real-time. However, the kV and MV beams cross shooting the target
      interfere with each other with beam scattering, which affects the quality of
      images. The success of this modality heavily relies on the image quality,
      especially the visibility of the target, which was investigated in this study.
      The kV and MV images were acquired for a gold implant marker that was used as a
      surrogate of the target and placed in an IMRT thorax phantom, a dynamic phantom,
      and a pelvis phantom to test the image quality in different situations. Contrast
      to-noise ration (CNR) was used to quantitatively describe the visibility of the
      target in the image. CNR can be obtained by statistical calculation from image
      processing and physics analysis with ion chamber measurement. The difference is
      described by contrast detection efficiency (CDE). By comparing the ratio (R) of
      CNR with and without the MV beam on, the MV beam scatter was found to have
      dramatically reduced the target visibility in the kV images (R=0.47), which was
      supported by an independent physics analysis that treats beam scatter as a noise.
      In contrast, the kV scatter effect on the MV images was minor (R=0.93). The
      effect of tumor motion was visible but tolerable for the target tracking purpose.
      CNR varied with different tumor sites and was lower for the pelvis than the
      thorax. Different kV imaging parameters such as kVp, mAs, and exposure time ms
      were tested for different cases. Considering a threshold of 1.0 CNR as a measure
      for the target visibility, a range of CNR from 1.3 to 4.2 was reached with
      appropriate tuning of those imaging parameters. This study has shown that CNR is
      a key parameter that can be used for assessing the visibility of the target in
      digital imaging and the quality of kV/MV images. It has also been shown that
      reasonable target visibility can be obtained using simultaneous kV-MV imaging for
      real-time target tracking.

PMID- 19175108
TI  - Correlative feature analysis on FFDM.
AB  - Identifying the corresponding images of a lesion in different views is an
      essential step in improving the diagnostic ability of both radiologists and
      computer-aided diagnosis (CAD) systems. Because of the nonrigidity of the breasts
      and the 2D projective property of mammograms, this task is not trivial. In this
      pilot study, we present a computerized framework that differentiates between
      corresponding images of the same lesion in different views and noncorresponding
      images, i.e., images of different lesions. A dual-stage segmentation method,
      which employs an initial radial gradient index (RGI) based segmentation and an
      active contour model, is applied to extract mass lesions from the surrounding
      parenchyma. Then various lesion features are automatically extracted from each of
      the two views of each lesion to quantify the characteristics of density, size,
      texture and the neighborhood of the lesion, as well as its distance to the
      nipple. A two-step scheme is employed to estimate the probability that the two
      lesion images from different mammographic views are of the same physical lesion.
      In the first step, a correspondence metric for each pairwise feature is estimated
      by a Bayesian artificial neural network (BANN). Then, these pairwise
      correspondence metrics are combined using another BANN to yield an overall
      probability of correspondence. Receiver operating characteristic (ROC) analysis
      was used to evaluate the performance of the individual features and the selected
      feature subset in the task of distinguishing corresponding pairs from
      noncorresponding pairs. Using a FFDM database with 123 corresponding image pairs
      and 82 noncorresponding pairs, the distance feature yielded an area under the ROC
      curve (AUC) of 0.81 +/- 0.02 with leave-one-out (by physical lesion) evaluation,
      and the feature metric subset, which included distance, gradient texture, and ROI
      based correlation, yielded an AUC of 0.87 +/- 0.02. The improvement by using
      multiple feature metrics was statistically significant compared to single feature
      performance.

PMID- 19175110
TI  - Cascaded systems analysis of the 3D noise transfer characteristics of flat-panel
      cone-beam CT.
AB  - The physical factors that govern 2D and 3D imaging performance may be understood
      from quantitative analysis of the spatial-frequency-dependent signal and noise
      transfer characteristics [e.g., modulation transfer function (MTF), noise-power
      spectrum (NPS), detective quantum efficiency (DQE), and noise-equivalent quanta
      (NEQ)] along with a task-based assessment of performance (e.g., detectability
      index). This paper advances a theoretical framework based on cascaded systems
      analysis for calculation of such metrics in cone-beam CT (CBCT). The model
      considers the 2D projection NPS propagated through a series of reconstruction
      stages to yield the 3D NPS and allows quantitative investigation of tradeoffs in
      image quality associated with acquisition and reconstruction techniques. While
      the mathematical process of 3D image reconstruction is deterministic, it is shown
      that the process is irreversible, the associated reconstruction parameters
      significantly affect the 3D DQE and NEQ, and system optimization should consider
      the full 3D imaging chain. Factors considered in the cascade include: system
      geometry; number of projection views; logarithmic scaling; ramp, apodization, and
      interpolation filters; 3D back-projection; and 3D sampling (noise aliasing). The
      model is validated in comparison to experiment across a broad range of dose,
      reconstruction filters, and voxel sizes, and the effects of 3D noise correlation
      on detectability are explored. The work presents a model for the 3D NPS, DQE, and
      NEQ of CBCT that reduces to conventional descriptions of axial CT as a special
      case and provides a fairly general framework that can be applied to the design
      and optimization of CBCT systems for various applications.

PMID- 19175111
TI  - Monte Carlo dosimetry for 125I and 103Pd eye plaque brachytherapy.
AB  - A Monte Carlo study of dosimetry for eye plaque brachytherapy is performed.
      BrachyDose, an EGSnrc user code which makes use of Yegin's multi-geometry
      package, is used to fully model 125I (model 6711) and 103Pd (model 200)
      brachytherapy seeds and the standardized plaques of the Collaborative Ocular
      Melanoma Study (COMS). Three-dimensional dose distributions in the eye region are
      obtained. In general, dose to water is scored; however, the implications of
      replacing water with eye tissues are explored. The effect of the gold alloy
      (Modulay) backing is investigated and the dose is found to be sensitive to the
      elemental composition of the backing. The presence of the silicone polymer
      (Silastic) seed carrier results in substantial dose decreases relative to water,
      particularly for 103Pd. For a 20 mm plaque with a Modulay backing and Silastic
      insert, fully loaded with 24 seeds, the dose decrease relative to water is of the
      order of 14% for 125I and 20% for 103Pd at a distance of 1 cm from the inner
      sclera along the plaque's central axis. For the configurations of seeds used in
      COMS plaques, interseed attenuation is a small effect within the eye region. The
      introduction of an air interface results in a dose reduction in its vicinity
      which depends on the plaque's position within the eye and the radionuclide.
      Introducing bone in the eye's vicinity also causes dose reductions. The dose
      distributions in the eye for the two different radionuclides are compared and,
      for the same prescription dose, 103Pd generally offers a lower dose to critical
      normal structures. BrachyDose is sufficiently fast to allow full Monte Carlo dose
      calculations for routine clinical treatment planning.

PMID- 19175112
TI  - Analytical optimization of digital subtraction mammography with contrast medium
      using a commercial unit.
AB  - Contrast-medium-enhanced digital mammography (CEDM) is an image subtraction
      technique which might help unmasking lesions embedded in very dense breasts.
      Previous works have stated the feasibility of CEDM and the imperative need of
      radiological optimization. This work presents an extension of a former analytical
      formalism to predict contrast-to-noise ratio (CNR) in subtracted mammograms. The
      goal is to optimize radiological parameters available in a clinical mammographic
      unit (x-ray tube anode/filter combination, voltage, and loading) by maximizing
      CNR and minimizing total mean glandular dose (D(gT)), simulating the experimental
      application of an iodine-based contrast medium and the image subtraction under
      dual-energy nontemporal, and single- or dual-energy temporal modalities. Total
      breast-entrance air kerma is limited to a fixed 8.76 mGy (1 R, similar to
      screening studies). Mathematical expressions obtained from the formalism are
      evaluated using computed mammographic x-ray spectra attenuated by an
      adipose/glandular breast containing an elongated structure filled with an
      iodinated solution in various concentrations. A systematic study of contrast, its
      associated variance, and CNR for different spectral combinations is performed,
      concluding in the proposal of optimum x-ray spectra. The linearity between
      contrast in subtracted images and iodine mass thickness is proven, including the
      determination of iodine visualization limits based on Rose's detection criterion.
      Finally, total breast-entrance air kerma is distributed between both images in
      various proportions in order to maximize the figure of merit CNR2/D(gT).
      Predicted results indicate the advantage of temporal subtraction (either single-
      or dual-energy modalities) with optimum parameters corresponding to high-voltage,
      strongly hardened Rh/Rh spectra. For temporal techniques, CNR was found to depend
      mostly on the energy of the iodinated image, and thus reduction in D(gT) could be
      achieved if the spectral energy of the noniodinated image is decreased and the
      breast-entrance air kerma is evenly distributed between both acquisitions.
      Predicted limits, in terms of iodine concentration, are found to guarantee the
      visualization of common clinical angiogenic concentrations in the breast.

PMID- 19175113
TI  - Clinical application of radiophotoluminescent glass dosimeter for dose
      verification of prostate HDR procedure.
AB  - High dose rate brachytherapy (HDR-BT) is one of the many modalities for prostate
      cancer treatment. Due to the nature of HDR-BT, in vivo dosimetry is feasible and
      can be used to verify consistent dose delivery. In order to validate a dose
      verification system for HDR-BT prostate cancer treatment, a radiophotoluminescent
      glass dosimeter (RPLGD) was used and the measurements were compared with those
      from a thermoluminescent dosimeter. The RPLGD shows many advantages in HDR-BT
      dose measurement, such as repeatability, stability, and small effective size.
      These advantages make the RPLGD a superior option for use as a dosimeter in HDR
      BT. The results described here show that the difference between the measured dose
      and the treatment planned dose is less than 5%. A Monte Carlo simulation for the
      dose was performed using Monte Carlo N -particle to investigate position error.
      This study concludes that the RPLGD is a promising and reliable dosimeter for HDR
      BT in vivo dosimetry with clinically acceptable accuracy.

PMID- 19175114
TI  - Model for the detection of signals in images with multiple suspicious locations.
AB  - A signal detection model is presented that combines a signal model and a noise
      model providing mathematical descriptions of the frequency of appearance of the
      signals, and of the signal-like features naturally occurring in the background.
      We derive expressions for the likelihood functions for the whole ensemble of
      observed suspicious locations, in various possible combinations of signals and
      false signal candidates. As a result, this formalism is able to describe several
      new types of detection tests using likelihood ratio statistics. We have a global
      image abnormality test and an individual signal detection test. The model also
      provides an alternative mechanism in which is selected the combination of signal
      and noise features candidates that has the maximum likelihood. These tests can be
      analyzed with a variety of operating characteristic curves (ROC, LROC, FROC,
      etc.). In the mathematical formalism of the model, all the details characterizing
      the suspicious features are reduced to a single scalar function, which we name
      the signal specificity function, representing the frequency that a signal takes a
      certain value relative to the frequency of having a false signal with the same
      value in an image of given size. The signal specificity function ranks the degree
      of suspiciousness of the features found, and can be used to unify into a single
      score all the suspicious feature characteristics, and then apply the usual
      decision conventions as in the Swensson's detection model [Med. Phys. 23, 1709
      1725 (1996)]. We present several examples in which these tests are compared. We
      also show how the signal specificity function can be used to model various
      degrees of accuracy of the observer's knowledge about image noise and signal
      statistical properties. Aspects concerning modeling of the human observer are
      also discussed.

PMID- 19175116
TI  - Implications of resolution and noise for in vivo micro-MRI of trabecular bone.
AB  - Osteoporotic bone loss is accompanied by impaired structural integrity of the
      trabecular network, leading to a decrease in the overall mechanical properties of
      the bone. The development of the "virtual bone biopsy" (VBB), a method combining
      magnetic resonance microimaging (microMRI) and digital image processing
      techniques, has previously been shown to quantify topology and scale of human
      trabecular bone noninvasively. The aim of this work was to determine the extent
      to which structural parameters derived from images acquired in the limited
      spatial resolution regime of in vivo imaging are sensitive to resolution and
      noise and further, whether under these conditions, a small amount of bone loss
      and its associated structural manifestations can be detected. Toward these goals
      3D models of trabecular bone representing multiple anatomic locations were
      generated on the basis of microCT images of human cadaveric bone cores. These
      images were binarized and the resulting data arrays representing pure bone
      (proton density=0) and pure marrow (proton density=255) subjected to simulated MR
      imaging by Cartesian sampling of k space, yielding, after 3D Fourier
      reconstruction, voxel sizes currently achievable in vivo. Subsequently, realistic
      levels of Gaussian noise were superimposed on the complex data and magnitude
      images were computed. The resulting images were subsequently VBB processed for a
      range of signal-to-noise ratio (SNR) values and image voxel sizes. For comparison
      of the predicted behavior to in vivo data, images from a recent patient study
      were evaluated as well. Systematic changes of the derived structural parameters
      changing progressively with decreasing SNR were noted, and it is shown that the
      errors are correctable using simple linear transformations, thereby allowing the
      data to be normalized. The predicted dependence of the structural parameters on
      SNR also closely parallel those observed in vivo. Finally, in order to assess the
      sensitivity of the VBB processing algorithms to detect bone loss during disease
      progression or regression in response to treatment, the high-resolution specimen
      data were subjected to 5% bone loss either by homogeneous or heterogeneous
      erosion and microMR images simulated at in vivo resolution and SNR. At typical in
      vivo SNR (SNR=12) and effective image resolution (160 microm isotropic and 137 x
      137 X 410 microm3), VBB algorithms were able to detect the structural
      implications of a 5% loss in bone volume fraction with high statistical
      significance.

PMID- 19175115
TI  - Pulmonary CT image registration and warping for tracking tissue deformation
      during the respiratory cycle through 3D consistent image registration.
AB  - Tracking lung tissues during the respiratory cycle has been a challenging task
      for diagnostic CT and CT-guided radiotherapy. We propose an intensity- and
      landmark-based image registration algorithm to perform image registration and
      warping of 3D pulmonary CT image data sets, based on consistency constraints and
      matching corresponding airway branchpoints. In this paper, we demonstrate the
      effectivenss and accuracy of this algorithm in tracking lung tissues by both
      animal and human data sets. In the animal study, the result showed a tracking
      accuracy of 1.9 mm between 50% functional residual capacity (FRC) and 85% total
      lung capacity (TLC) for 12 metal seeds implanted in the lungs of a breathing
      sheep under precise volume control using a pulmonary ventilator. Visual
      inspection of the human subject results revealed the algorithm's potential not
      only in matching the global shapes, but also in registering the internal
      structures (e.g., oblique lobe fissures, pulmonary artery branches, etc.). These
      results suggest that our algorithm has significant potential for warping and
      tracking lung tissue deformation with applications in diagnostic CT, CT-guided
      radiotherapy treatment planning, and therapeutic effect evaluation.

PMID- 19175118
TI  - Feasibility study for linac-based intensity modulated total marrow irradiation.
AB  - Total body irradiation (TBI) is used as a preconditioning regimen prior to bone
      marrow transplant for treatment of hematologic malignancies. During TBI, large
      volumes of normal tissue are irradiated, and this can lead to toxicities, most
      significantly in the lungs. Intensity modulated total marrow irradiation (IMTMI)
      may be able to reduce these toxicities by directly targeting the bone marrow
      while minimizing the dose to critical structures. The goal of this study was to
      assess the feasibility of IMTMI by following the planning and delivery process
      for a Rando phantom. A three isocenter technique was used to provide a full body
      plan for treatment on a linear accelerator. Thermoluminescent detectors (TLDs)
      were placed at 22 positions throughout the phantom to compare the delivered doses
      to the planned doses. Individual intensity modulated radiation therapy
      verification plans were delivered to a solid water phantom for the three
      isocenters, and doses measured from an ion chamber and film were compared to the
      planned doses. The treatment plan indicated that target coverage was achieved
      with this IMTMI technique, and that the doses to critical structures were reduced
      by 29%-65% compared to conventional TBI. TLD readings demonstrated accurate dose
      delivery, with an average difference of 3.5% from the calculated dose. Ion
      chamber readings for the verification plans were all within 3% of the expected
      dose, and film measurements showed accurate dose distributions. Results from this
      study suggest that IMTMI using the three isocenter technique can be accurately
      delivered and may result in substantial dose reductions to critical structures.

PMID- 19175117
TI  - Quality and accuracy of cone beam computed tomography gated by active breathing
      control.
AB  - The purpose of this study was to evaluate the quality and accuracy of cone beam
      computed tomography (CBCT) gated by active breathing control (ABC), which may be
      useful for image guidance in the presence of respiration. Comparisons were made
      between conventional ABC-CBCT (stop and go), fast ABC-CBCT (a method to speed up
      the acquisition by slowing the gantry instead of stopping during free breathing),
      and free breathing respiration correlated CBCT. Image quality was assessed in
      phantom. Accuracy of reconstructed voxel intensity, uniformity, and root mean
      square error were evaluated. Registration accuracy (bony and soft tissue) was
      quantified with both an anthropomorphic and a quality assurance phantom. Gantry
      angle accuracy was measured with respect to gantry speed modulation. Conventional
      ABC-CBCT scan time ranged from 2.3 to 5.8 min. Fast ABC-CBCT scan time ranged
      from 1.4 to 1.8 min, and respiratory correlated CBCT scans took 2.1 min to
      complete. Voxel intensity value for ABC gated scans was accurate relative to a
      normal clinical scan with all projections. Uniformity and root mean square error
      performance degraded as the number of projections used in the reconstruction of
      the fast ABC-CBCT scans decreased (shortest breath hold, longest free breathing
      segment). Registration accuracy for small, large, and rotational corrections was
      within 1 mm and 1 degrees. Gantry angle accuracy was within 1 degrees for all
      scans. For high-contrast targets, performance for image-guidance purposes was
      similar for fast and conventional ABC-CBCT scans and respiration correlated CBCT.

PMID- 19175119
TI  - A comparison of daily megavoltage CT and ultrasound image guided radiation
      therapy for prostate cancer.
AB  - In order to quantify the differences between ultrasound-imaging and megavoltage
      CT (MVCT) daily prostate localization in prostate-cancer radiotherapy and their
      dosimetric impacts, daily shifts were analyzed for a total of 140 prostate cancer
      patients; 106 positioned using ultrasound-based imaging [B-mode Acquisition and
      Targeting (BAT)], and 34 using the MVCT from a TomoTherapy Hi-Art unit. The
      shifts indicated by the two systems were compared statistically along the
      right/left (R/L), superior/inferior (S/I), and anterior/posterior (A/P)
      directions. The systematic and random variations among the daily alignments were
      calculated. Margins to account for these shifts were estimated. The mean shifts
      and standard deviations along the R/L, S/I, and A/P directions were -0.11 +/-
      3.80, 0.67 +/- 4.67, and 2.71+/- 6.31 mm for BAT localizations and -0.98 +/-
      5.13, 0.27 +/- 3.35, and 1.00 +/- 4.22 mm for MVCT localizations, respectively.
      The systematic and random variations in daily shifts based on MVCT were generally
      smaller than those based on BAT, especially along the A/P direction. A t-test
      showed this difference to be statistically significant. The planning target
      volume margins in the A/P direction estimated to account for daily variations
      were 8.81 and 14.66 mm based on MVCT and BAT data, respectively. There was no
      statistically significant difference in the daily prostate movement pattern
      between the first few fractions and the remaining fractions. Dosimetric
      comparison of MVCT and BAT prostate alignments was performed for seven fractions
      from a patient. The degradation from the plan caused by the MVCT alignment is
      trivial, while that by BAT is substantial. The MVCT technique results in smaller
      variations in daily shifts than ultrasound imaging, indicating that MVCT is more
      reliable and precise for prostate localization. Ultrasound-based localization may
      overestimate the daily prostate motion, particularly in the A/P direction,
      negatively impacting prostate dose coverage and rectal sparing.

PMID- 19175120
TI  - Accuracy of EGSnrc calculations at 60Co energies for the response of ion chambers
      configured with various wall materials and cavity dimensions.
AB  - In this investigation, five experimental data sets are used to evaluate the
      ability of the EGSnrc Monte Carlo code to calculate the change in chamber
      response associated with changes in wall material and cavity dimension at 60Co
      energies. Calculations of the ratios of response per unit mass of air as a
      function of cavity volume for walls ranging from polystyrene to lead are
      generally within 1%-3% of experiments. A few exceptions, which are discussed,
      include 20%-30% discrepancies with experiments involving lead-walled chambers
      used by Attix et al. [J. Res. Natl. Bur. Stand. 60, 235-243 (1958)] and Cormack
      and Johns [Radiat. Res. 1, 133-157 (1954)], and 5% discrepancies for the graphite
      chamber of Attix et al. (relative to data for other wall materials). Simulations
      of the experiment by Whyte [Radiat. Res. 6, 371-379 (1957)], which varied cavity
      air pressure in a large cylindrical chamber, are generally within 0.5%
      (wall/electrode materials ranging from beryllium to copper). In all cases, the
      agreement between measurements and EGSnrc calculations is much better when the
      response as a function of cavity height or air pressure is considered for each
      wall material individually. High-precision measurements [Burns et al., Phys. Med.
      Biol. 52, 7125-7135 (2007)] of the response per unit mass as a function of cavity
      height for a graphite chamber are also accurately reproduced, and validate
      previous tests of the transport mechanics of EGSnrc. Based on the general
      agreement found in this work between corresponding experimental results and
      EGSnrc calculations it can be concluded that EGSnrc can reliably be used to
      calculate changes in response with changes in various wall materials and cavity
      dimensions at 60Co energies within a accuracy of a few percent or less.

PMID- 19175121
TI  - Anniversary paper: A sampling of novel technologies and the role of medical
      physicists in radiation oncology.
AB  - Physicists have and continue to play a major role in the creation and
      introduction of novel technology into medical care. This review covers some of
      the highlights of contributions of medical physicists to the field of radiation
      oncology during the history of the AAPM. While not comprehensive, the broad scope
      of developments and their impact hints at the importance of the medical physicist
      in advancing the field in the past, present, and future.

PMID- 19175122
TI  - The future of heavy ion radiotherapy.
AB  - Currently, there is an increasing interest in heavy ion radiotherapy (RT) and a
      number of new facilities are being installed in Europe and Japan. This
      development is accompanied by intensive technical, physical, and clinical
      research. The authors identify six research fields where progress is likely and
      propose a thesis on the expected achievements for each of the fields: (1)
      Synchrotrons with active energy variation and three-dimensional beam scanning
      will be the standard in ion beam RT. (2) Common standards for precise
      measurement, prescription, and reporting of dose will be available. (3) Intensity
      modulated particle therapy will be state-of-the-art. (4) Time-adaptive treatments
      of moving targets will be feasible. (5) Therapeutic effectiveness of heavy ions
      will be known for the most important indications while cost effectiveness will
      remain to be shown. (6) The potential of high-linear energy transfer radiation
      will be known. The rationale for each of these theses is described.

PMID- 19175123
TI  - Scale-based scatter correction for computer-aided polyp detection in CT
      colonography.
AB  - CT colonography (CTC) is a feasible and minimally invasive method for the
      detection of colorectal polyps and cancer screening. Computer-aided detection
      (CAD) of polyps can improve consistency and sensitivity of virtual colonoscopy
      interpretation and reduce interpretation burden. However, high-density orally
      administered contrast agents have scatter effects on neighboring tissues. The
      scattering manifests itself as an artificial elevation in the observed CT
      attenuation values of the neighboring tissues. This pseudoenhancement phenomenon
      presents a problem for the application of computer-aided polyp detection,
      especially when polyps are submerged in the contrast agents. The authors have
      developed a scale-based correction method that minimizes scatter effects in CTC
      data by subtraction of the estimated scatter components from observed CT
      attenuations. By bringing a locally adaptive structure, object scale, into the
      correction framework, the region of neighboring tissues affected by contrast
      agents is automatically specified and adaptively changed in different parts of
      the image. The method was developed as one preprocessing step in the authors' CAD
      system and was tested by using leave-one-patient-out evaluation on 56 clinical
      CTC scans (supine or prone) from 28 patients. There were 50 colonoscopy-confirmed
      polyps measuring 6-9 mm. Visual evaluation indicated that the method reduced CT
      attenuation of pseudoenhanced polyps to the usual polyp Hounsfield unit range
      without affecting luminal air regions. For polyps submerged in contrast agents,
      the sensitivity of CAD with correction is increased 24% at a rate of ten false
      positive detections per scan. For all polyps within 6-9 mm, the sensitivity of
      the authors' CAD with scatter correction is increased 8% at a rate of ten false
      positive detections per scan. The authors' results indicated that CAD with this
      correction method as a preprocessing step can yield a high sensitivity and a
      relatively low FP rate in CTC.

PMID- 19175124
TI  - The optimal optical readout for the x-ray light valve--document scanners.
AB  - The x-ray light valve (XLV) is a novel, potentially low-cost, x-ray detector that
      converts an x-ray exposure into an optical image stored in a liquid crystal cell.
      This optical image is then transferred from the liquid crystal cell to a computer
      through an optical-to-digital imaging readout system. Previously, CCD-based
      cameras were used for the optical readout, but recently it was proposed that an
      inexpensive optical scanner, such as an office document scanner, is a better
      match to the optical properties of the XLV. A methodology for characterizing a
      document scanner's ability to produce medical quality images from the XLV is
      outlined and tested on a particular scanner (Canon LiDE 30). This scanner was
      shown to have key characteristics of a medical device-a linear response, dynamic
      range sufficient for chest radiography (although not mammography) in a single
      pass, and an MTF and NPS that exceed the requirements for all medical
      applications of the scanner. This combination of criteria shows that a document
      scanner can be used as a digitization method for the XLV.

PMID- 19175125
TI  - Locating and targeting moving tumors with radiation beams.
AB  - The current climate of rapid technological evolution is reflected in newer and
      better methods to modulate and direct radiation beams for cancer therapy. This
      Vision 20/20 paper focuses on part of this evolution, locating and targeting
      moving tumors. The two processes are somewhat independent and in principle
      different implementations of the locating and targeting processes can be
      interchanged. Advanced localization and targeting methods have an impact on
      treatment planning and also present new challenges for quality assurance (QA),
      that of verifying real-time delivery. Some methods to locate and target moving
      tumors with radiation beams are currently FDA approved for clinical use-and this
      availability and implementation will increase with time. Extensions of current
      capabilities will be the integration of higher order dimensionality, such as
      rotation and deformation in addition to translation, into the estimate of the
      patient pose and real-time reoptimization and adaption of delivery to the
      dynamically changing anatomy of cancer patients.

PMID- 19175126
TI  - Investigation of psychophysical similarity measures for selection of similar
      images in the diagnosis of clustered microcalcifications on mammograms.
AB  - The presentation of images with lesions of known pathology that are similar to an
      unknown lesion may be helpful to radiologists in the diagnosis of challenging
      cases for improving the diagnostic accuracy and also for reducing variation among
      different radiologists. The authors have been developing a computerized scheme
      for automatically selecting similar images with clustered microcalcifications on
      mammograms from a large database. For similar images to be useful, they must be
      similar from the point of view of the diagnosing radiologists. In order to select
      such images, subjective similarity ratings were obtained for a number of pairs of
      clustered microcalcifications by breast radiologists for establishment of a "gold
      standard" of image similarity, and the gold standard was employed for
      determination and evaluation of the selection of similar images. The images used
      in this study were obtained from the Digital Database for Screening Mammography
      developed by the University of South Florida. The subjective similarity ratings
      for 300 pairs of images with clustered microcalcifications were determined by ten
      breast radiologists. The authors determined a number of image features which
      represent the characteristics of clustered microcalcifications that radiologists
      would use in their diagnosis. For determination of objective similarity measures,
      an artificial neural network (ANN) was employed. The ANN was trained with the
      average subjective similarity ratings as teacher and selected image features as
      input data. The ANN was trained to learn the relationship between the image
      features and the radiologists' similarity ratings; therefore, once the training
      was completed, the ANN was able to determine the similarity, called a
      psychophysical similarity measure, which was expected to be close to
      radiologists' impressions, for an unknown pair of clustered microcalcifications.
      By use of a leave-one-out test method, the best combination of features was
      selected. The correlation coefficient between the gold standard and the
      psychophysical similarity measure through the use of seven features was
      relatively high (r=0.71) and was comparable to the correlation coefficients
      between the ratings by one radiologist and the average ratings by nine
      radiologists (r=0.69 +/- 0.07). The correlation coefficient was improved compared
      to that of a distance-based method (r=0.58). The result indicated that similar
      images selected by the psychophysical similarity measure may be useful to
      radiologists in the diagnosis of clustered microcalcifications on mammograms.

PMID- 19175127
TI  - DOT guided fluorescence molecular tomography of arbitrarily shaped objects.
AB  - The authors demonstrate an approach for truly quantitative three-dimensional
      fluorescence molecular tomography (FMT) of arbitrarily shaped objects where the
      distribution of optical properties is obtained using diffuse optical tomography
      (DOT). The method is tested and evaluated using phantom geometries mimicking
      mouse anatomic structures. The experiments were conducted using the authors'
      optical-fiber-free, multiangle transmission system. The results indicate that
      with the knowledge of optical property distribution, the accuracy of the
      recovered fluorophore absorption coefficient (mu(a(x-->m of indocyanine green is
      improved significantly over that without such a priori information using the
      authors' finite element reconstruction approach. In particular, the absolute
      value of mu(a(x-->m)) from their DOT guided FMT is quantitatively consistent with
      that obtained with spectroscopic methods.

PMID- 19175128
TI  - Technical note: rapid prototyping of 3D grid arrays for image guided therapy
      quality assurance.
AB  - Three dimensional grid phantoms offer a number of advantages for measuring
      imaging related spatial inaccuracies for image guided surgery and radiotherapy.
      The authors examined the use of rapid prototyping technology for directly
      fabricating 3D grid phantoms from CAD drawings. We tested three different
      fabrication process materials, photopolymer jet with acrylic resin (PJ/AR),
      selective laser sintering with polyamide (SLS/P), and fused deposition modeling
      with acrylonitrile butadiene styrene (FDM/ABS). The test objects consisted of
      rectangular arrays of control points formed by the intersections of posts and
      struts (2 mm rectangular cross section) and spaced 8 mm apart in the x, y, and z
      directions. The PJ/AR phantom expanded after immersion in water which resulted in
      permanent warping of the structure. The surface of the FDM/ABS grid exhibited a
      regular pattern of depressions and ridges from the extrusion process. SLS/P
      showed the best combination of build accuracy, surface finish, and stability.
      Based on these findings, a grid phantom for assessing machine-dependent and frame
      induced MR spatial distortions was fabricated to be used for quality assurance in
      stereotactic neurosurgical and radiotherapy procedures. The spatial uniformity of
      the SLS/P grid control point array was determined by CT imaging (0.6 x 0.6 x
      0.625 mm3 resolution) and found suitable for the application, with over 97.5% of
      the control points located within 0.3 mm of the position specified in CAD drawing
      and none of the points off by more than 0.4 mm. Rapid prototyping is a flexible
      and cost effective alternative for development of customized grid phantoms for
      medical physics quality assurance.

PMID- 19175129
TI  - Overview of patient dosimetry in diagnostic radiology in the USA for the past 50
      years.
AB  - This review covers the role of medical physics in addressing issues directly
      related to patient dosimetry in radiography, fluoroscopy, mammography, and CT.
      The sections on radiography and fluoroscopy radiation doses review the changes
      that have occurred during the last 50 to 60 years. A number of technological
      improvements have contributed to both a significant reduction in patient and
      staff radiation doses and improvements to the image quality during this period of
      time. There has been a transition from film-screen radiography with hand dip film
      processing to electronic digital imaging utilizing CR and DR. Similarly,
      fluoroscopy has progressed by directly viewing image intensifiers in darkened
      rooms to modern flat panel image receptor systems utilizing pulsed radiation,
      automated variable filtration, and digitally processed images. Mammography is one
      of the most highly optimized imaging procedures performed, because it is a
      repetitive screening procedure that results in annual radiation exposure.
      Mammography is also the only imaging procedure in the United States in which the
      radiation dose is regulated by the federal government. Consequently, many medical
      physicists have studied the dosimetry associated with screen-film and digital
      mammography. In this review, a brief history of mammography dose assessment by
      medical physicists is discussed. CT was introduced into clinical practice in the
      early 1970s, and has grown into one of the most important modalities available
      for diagnostic imaging. CT dose quantities and measurement techniques are
      described, and values of radiation dose for different types of scanner are
      presented. Organ and effective doses to adult patients are surveyed from the
      earliest single slice scanners, to the latest versions that include up to two x
      ray tubes and can incorporate as many as 256 detector channels. An overview is
      provided of doses received by pediatric patients undergoing CT examinations, as
      well as methods, and results, of studies performed to assess the radiation
      absorbed by the conceptus of pregnant patients.

PMID- 19175130
TI  - Response of an implantable MOSFET dosimeter to 192Ir HDR radiation.
AB  - New in vivo dosimetry methods would be useful for clinical HDR brachytherapy. An
      implantable MOSFET Dose Verification System designed by Sicel Technologies, Inc.
      was examined for use with 192Ir HDR applications. This investigation demonstrated
      that varying the dose rate from 22 to 84 cGy/min did not change detector
      response. The detectors exhibited a higher sensitivity to 192Ir energies than
      60Co energies. A nonlinear accumulated dose effect was characterized by three
      third-order polynomials fit to data from detectors placed at three different
      distances from the source. The detectors were found to have minimal rotational
      angular dependence. A strong longitudinal angular dependence was found when the
      detector's copper coil and electronics assembly were aligned between the MOSFETs
      and incident radiation. This orientation showed a 16% decrease in response
      relative to other orientations tested.

PMID- 19175131
TI  - Dose calculation with respiration-averaged CT processed from cine CT without a
      respiratory surrogate.
AB  - Dose calculation for thoracic radiotherapy is commonly performed on a free
      breathing helical CT despite artifacts caused by respiratory motion. Four
      dimensional computed tomography (4D-CT) is one method to incorporate motion
      information into the treatment planning process. Some centers now use the
      respiration-averaged CT (RACT), the pixel-by-pixel average of the ten phases of
      4D-CT, for dose calculation. This method, while sparing the tedious task of 4D
      dose calculation, still requires 4D-CT technology. The authors have recently
      developed a means to reconstruct RACT directly from unsorted cine CT data from
      which 4D-CT is formed, bypassing the need for a respiratory surrogate. Using RACT
      from cine CT for dose calculation may be a means to incorporate motion
      information into dose calculation without performing 4D-CT. The purpose of this
      study was to determine if RACT from cine CT can be substituted for RACT from 4D
      CT for the purposes of dose calculation, and if increasing the cine duration can
      decrease differences between the dose distributions. Cine CT data and
      corresponding 4D-CT simulations for 23 patients with at least two breathing
      cycles per cine duration were retrieved. RACT was generated four ways: First from
      ten phases of 4D-CT, second, from 1 breathing cycle of images, third, from 1.5
      breathing cycles of images, and fourth, from 2 breathing cycles of images. The
      clinical treatment plan was transferred to each RACT and dose was recalculated.
      Dose planes were exported at orthogonal planes through the isocenter (coronal,
      sagittal, and transverse orientations). The resulting dose distributions were
      compared using the gamma index within the planning target volume (PTV). Failure
      criteria were set to 2%/1 mm. A follow-up study with 50 additional lung cancer
      patients was performed to increase sample size. The same dose recalculation and
      analysis was performed. In the primary patient group, 22 of 23 patients had 100%
      of points within the PTV pass y criteria. The average maximum and mean y indices
      were very low (well below 1), indicating good agreement between dose
      distributions. Increasing the cine duration generally increased the dose
      agreement. In the follow-up study, 49 of 50 patients had 100% of points within
      the PTV pass the y criteria. The average maximum and mean y indices were again
      well below 1, indicating good agreement. Dose calculation on RACT from cine CT is
      negligibly different from dose calculation on RACT from 4D-CT. Differences can be
      decreased further by increasing the cine duration of the cine CT scan.

PMID- 19175132
TI  - Optimization of super-resolution processing using incomplete image sets in PET
      imaging.
AB  - Super-resolution (SR) techniques are used in PET imaging to generate a high
      resolution image by combining multiple low-resolution images that have been
      acquired from different points of view (POVs). The number of low-resolution
      images used defines the processing time and memory storage necessary to generate
      the SR image. In this paper, the authors propose two optimized SR implementations
      (ISR-1 and ISR-2) that require only a subset of the low-resolution images (two
      sides and diagonal of the image matrix, respectively), thereby reducing the
      overall processing time and memory storage. In an N x N matrix of low-resolution
      images, ISR-1 would be generated using images from the two sides of the N x N
      matrix, while ISR-2 would be generated from images across the diagonal of the
      image matrix. The objective of this paper is to investigate whether the two
      proposed SR methods can achieve similar performance in contrast and signal-to
      noise ratio (SNR) as the SR image generated from a complete set of low-resolution
      images (CSR) using simulation and experimental studies. A simulation, a point
      source, and a NEMA/IEC phantom study were conducted for this investigation. In
      each study, 4 (2 x 2) or 16 (4 x 4) low-resolution images were reconstructed from
      the same acquired data set while shifting the reconstruction grid to generate
      images from different POVs. SR processing was then applied in each study to
      combine all as well as two different subsets of the low-resolution images to
      generate the CSR, ISR-1, and ISR-2 images, respectively. For reference purpose, a
      native reconstruction (NR) image using the same matrix size as the three SR
      images was also generated. The resultant images (CSR, ISR-1, ISR-2, and NR) were
      then analyzed using visual inspection, line profiles, SNR plots, and background
      noise spectra. The simulation study showed that the contrast and the SNR
      difference between the two ISR images and the CSR image were on average 0.4% and
      0.3%, respectively. Line profiles of the point source study showed that the three
      SR images exhibited similar signal amplitudes and FWHM. The NEMA/IEC study showed
      that the average difference in SNR among the three SR images was 2.1% with
      respect to one another and they contained similar noise structure. ISR-1 and ISR
      2 can be used to replace CSR, thereby reducing the total SR processing time and
      memory storage while maintaining similar contrast, resolution, SNR, and noise
      structure.

PMID- 19175133
TI  - Prospects of photoacoustic tomography.
AB  - Commercially available high-resolution three-dimensional optical imaging
      modalities-including confocal microscopy, two-photon microscopy, and optical
      coherence tomography-have fundamentally impacted biomedicine. Unfortunately, such
      tools cannot penetrate biological tissue deeper than the optical transport mean
      free path (approximately 1 mm in the skin). Photoacoustic tomography, which
      combines strong optical contrast and high ultrasonic resolution in a single
      modality, has broken through this fundamental depth limitation and achieved
      superdepth high-resolution optical imaging. In parallel, radio frequency-or
      microwave-induced thermoacoustic tomography is being actively developed to
      combine radio frequency or microwave contrast with ultrasonic resolution. In this
      Vision 20/20 article, the prospects of photoacoustic tomography are envisaged in
      the following aspects: (1) photoacoustic microscopy of optical absorption
      emerging as a mainstream technology, (2) melanoma detection using photoacoustic
      microscopy, (3) photoacoustic endoscopy, (4) simultaneous functional and
      molecular photoacoustic tomography, (5) photoacoustic tomography of gene
      expression, (6) Doppler photoacoustic tomography for flow measurement, (7)
      photoacoustic tomography of metabolic rate of oxygen, (8) photoacoustic mapping
      of sentinel lymph nodes, (9) multiscale photoacoustic imaging in vivo with common
      signal origins, (10) simultaneous photoacoustic and thermoacoustic tomography of
      the breast, (11) photoacoustic and thermoacoustic tomography of the brain, and
      (12) low-background thermoacoustic molecular imaging.

PMID- 19175134
TI  - A method for quantitative assessment of renal function using dynamic contrast
      enhanced computed tomography: evaluation of drug-induced nephrotoxicity in rats.
AB  - The authors developed a method to quantitatively evaluate renal function using
      dynamic contrast-enhanced computed tomography (DCE-CT) and a compartment model.
      They applied this method to evaluation of drug-induced nephrotoxicity in rats.
      They performed the DCE-CT studies using a total of 36 male Sprague-Dawley rats
      (n=9 for control and n=27 for treatment). The rats in the drug-treated groups
      were given 1.8 mg/kg/day of cis-dichlorodiammineplatinum (cisplatin)
      intraperitoneally every other day twice (n=9), four times (n=9), or six times
      (n=9). The rate constants for the transfer of the contrast agent (CA) from the
      intravascular space to the renal corpuscle and tubular space via glomerular
      filtration (K1), outflow of the CA from the renal tubules (k2), and the fraction
      of blood volume (f) were estimated from the DCE-CT data, and their functional
      images were generated using the linear least squares method. When estimating the
      above parameters, the partial volume effect (PVE) on the arterial input function
      was corrected using a calibration curve obtained by phantom experiments. The
      endogenous creatinine clearance (Ccr) was also measured for comparison. The K1
      images became lower and more heterogeneous and the K1 values decreased
      significantly with increasing cisplatin injection number (3.20+/-0.73, 2.49+/
      0.75, 1.80+/-0.36, and 1.27+/-0.47 ml/ml/min for control, two-, four-, and six
      times treated groups, respectively). When the PVE was not corrected, the K1
      values were overestimated by 15+/-3% as compared with the case when the PVE was
      corrected. There was a good correlation between K1 and Ccr (r=0.903 and 0.901 for
      cases with and without correction of PVE, respectively). In conclusion, the
      authors' method using DCE-CT appears to be useful for quantitatively evaluating
      the extent of renal dysfunction such as renal damage due to drug-induced
      nephrotoxicity.

PMID- 19175135
TI  - Low dose megavoltage cone beam computed tomography with an unflattened 4 MV beam
      from a carbon target.
AB  - Megavoltage cone beam computed tomography (MVCBCT) is routinely used for
      visualizing anatomical structures and implanted fiducials for patient positioning
      in radiotherapy. MVCBCT using a 6 MV treatment beam with high atomic number (Z)
      target and flattening filter in the beamline, as done conventionally, has lower
      image quality than can be achieved with a MV beam due to heavy filtration of the
      low-energy bremsstrahlung. The unflattened beam of a low Z target has an
      abundance of diagnostic energy photons, detected with modern flat panel detectors
      with much higher efficiency given the same dose to the patient. This principle
      guided the development of a new megavoltage imaging beamline (IBL) for a
      commercial radiotherapy linear accelerator. A carbon target was placed in one of
      the electron primary scattering foil slots on the target-foil slide. A PROM on a
      function controller board was programed to put the carbon target in place for
      MVCBCT. A low accelerating potential of 4.2 MV was used for the IBL to restrict
      leakage of primary electrons through the target such that dose from x rays
      dominated the signal in the monitor chamber and the patient surface dose. Results
      from phantom and cadaver images demonstrated that the IBL had much improved image
      quality over the treatment beam. For similar imaging dose, the IBL improved the
      contrast-to-noise ratio by as much as a factor of 3 in soft tissue over that of
      the treatment beam. The IBL increased the spatial resolution by about a factor of
      2, allowing the visualization of finer anatomical details. Images of the cadaver
      contained useful information with doses as low as 1 cGy. The IBL may be installed
      on certain models of linear accelerators without mechanical modification and
      results in significant improvement in the image quality with the same dose, or
      images of the same quality with less than one-third of the dose.

PMID- 19175136
TI  - An EM approach to MAP solution of segmenting tissue mixture percentages with
      application to CT-based virtual colonoscopy.
AB  - Electronic colon cleansing (ECC) is an emerging technique developed to segment
      the colon lumen from a patient's abdominal computed tomography colonography (CTC)
      images. However, the residue stool and fluid tagged by contrast materials as well
      as mixed tissue distribution with partial volume (PV) effect impose several
      challenges for ECC, resulting in incomplete and overcomplete cleansings. To
      address the PV effect, this work investigated an improved maximum a posteriori
      expectation-maximization (MAP-EM) image segmentation algorithm which
      simultaneously estimates tissue mixture percentages within each image voxel and
      statistical model parameters for the tissue distribution. Given the segmented
      tissue mixture information beyond the image voxel level, not only the PV effect
      has been satisfactorily addressed as a particular case of tissue mixture problem,
      but incomplete and overcomplete ECC causes could also be maximally avoided. For
      clinical application to CTC that involves several issues transferring from
      theoretical analysis to practical validation, an innovative initialization
      procedure and refined estimation strategy were proposed to build an ECC pipeline
      based on the MAP-EM segmentation. The pipeline was evaluated based on 52 patient
      CTC studies, downloaded from the website of the Virtual Colonoscopy Screening
      Resource Center, by two radiologists. A noticeable improvement over the authors'
      previous ECC pipeline was documented. Several typical cases were also presented
      to show visually the improved performance of the presented ECC pipeline.

PMID- 19175138
TI  - Patient-specific dose estimation for pediatric chest CT.
AB  - Current methods for organ and effective dose estimations in pediatric CT are
      largely patient generic. Physical phantoms and computer models have only been
      developed for standard/limited patient sizes at discrete ages (e.g., 0, 1, 5, 10,
      15 years old) and do not reflect the variability of patient anatomy and body
      habitus within the same size/age group. In this investigation, full-body computer
      models of seven pediatric patients in the same size/protocol group (weight: 11.9
      18.2 kg) were created based on the patients' actual multi-detector array CT
      (MDCT) data. Organs and structures in the scan coverage were individually
      segmented. Other organs and structures were created by morphing existing adult
      models (developed from visible human data) to match the framework defined by the
      segmented organs, referencing the organ volume and anthropometry data in ICRP
      Publication 89. Organ and effective dose of these patients from a chest MDCT scan
      protocol (64 slice LightSpeed VCT scanner, 120 kVp, 70 or 75 mA, 0.4 s gantry
      rotation period, pitch of 1.375, 20 mm beam collimation, and small body scan
      field-of-view) was calculated using a Monte Carlo program previously developed
      and validated to simulate radiation transport in the same CT system. The seven
      patients had normalized effective dose of 3.7-5.3 mSv/100 mAs (coefficient of
      variation: 10.8%). Normalized lung dose and heart dose were 10.4-12.6 mGy/100 mAs
      and 11.2-13.3 mGy/100 mAs, respectively. Organ dose variations across the
      patients were generally small for large organs in the scan coverage (<7%), but
      large for small organs in the scan coverage (9%-18%) and for partially or
      indirectly exposed organs (11%-77%). Normalized effective dose correlated weakly
      with body weight (correlation coefficient: r=-0.80). Normalized lung dose and
      heart dose correlated strongly with mid-chest equivalent diameter (lung: r=-0.99,
      heart: r=-0.93); these strong correlation relationships can be used to estimate
      patient-specific organ dose for any other patient in the same size/protocol group
      who undergoes the chest scan. In summary, this work reported the first assessment
      of dose variations across pediatric CT patients in the same size/protocol group
      due to the variability of patient anatomy and body habitus and provided a
      previously unavailable method for patient-specific organ dose estimation, which
      will help in assessing patient risk and optimizing dose reduction strategies,
      including the development of scan protocols.

PMID- 19175139
TI  - A novel method to calibrate DOI function of a PET detector with a dual-ended
      scintillator readout.
AB  - The detection of depth-of-interaction (DOI) is a critical detector capability to
      improve the PET spatial resolution uniformity across the field-of-view and will
      significantly enhance, in particular, small bore system performance for brain,
      breast, and small animal imaging. One promising technique of DOI detection is to
      use dual-ended-scintillator readout that uses two photon sensors to detect
      scintillation light from both ends of a scintillator array and estimate DOI based
      on the ratio of signals (similar to Anger logic). This approach needs a careful
      DOI function calibration to establish accurate relationship between DOI and
      signal ratios, and to recalibrate if the detection condition is shifted due to
      the drift of sensor gain, bias variations, or degraded optical coupling, etc.
      However, the current calibration method that uses coincident events to locate
      interaction positions inside a single scintillator crystal has severe drawbacks,
      such as complicated setup, long and repetitive measurements, and being prone to
      errors from various possible misalignments among the source and detector
      components. This method is also not practically suitable to calibrate multiple
      DOI functions of a crystal array. To solve these problems, a new method has been
      developed that requires only a uniform flood source to irradiate a crystal array
      without the need to locate the interaction positions, and calculates DOI
      functions based solely on the uniform probability distribution of interactions
      over DOI positions without knowledge or assumption of detector responses.
      Simulation and experiment have been studied to validate the new method, and the
      results show that the new method, with a simple setup and one single measurement,
      can provide consistent and accurate DOI functions for the entire array of
      multiple scintillator crystals. This will enable an accurate, simple, and
      practical DOI function calibration for the PET detectors based on the design of
      dual-ended-scintillator readout. In addition, the new method can be generally
      applied to calibrating other types of detectors that use the similar dual-ended
      readout to acquire the radiation interaction position.

PMID- 19175140
TI  - An experimental palladium-103 seed (OptiSeedexp) in a biocompatible polymer
      without a gold marker: characterization of dosimetric parameters including the
      interseed effect.
AB  - Permanent implantation of 125I (iodine) or 103Pd (palladium) sources is a popular
      treatment option in the management of early stage prostate cancer. New sources
      are being developed, some of which are being marketed for different clinical
      applications. A new technique of adjuvant stereotactic permanent seed breast
      implant, similar to that used in the treatment of prostate cancer, has been
      proposed by [N. Jansen et al., Int. J. Radiat. Oncol. Biol. Phys. 67, 1052-1058
      (2007)] with encouraging results. The presence of artifacts from the metallic
      seeds, however, can disturb follow-up imaging. The development of plastic seeds
      has reduced these artifacts. This paper presents a feasibility study of the
      advantages of palladium-103 seeds, encapsulated with a biocompatible polymer, for
      future clinical applications, and on the effect of the gold marker on the
      dosimetric characteristics of such seeds. Experimental palladium seeds,
      OptiSeedexp, were manufactured by International Brachytherapy (IBt), Seneffe,
      Belgium, from a biocompatible polymer, including the marker. Apart from the
      absence of a gold marker, the studied seed has an identical design to the
      OptiSeed103 [Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311
      321 (2005)]. Polymer encapsulation was preferred by IBt in order to reduce the
      quantity of radioactive material needed for a given dose rate and to reduce the
      anisotropy of the radiation field around the seed. In addition, this design is
      intended to decrease the interseed effects that can occur as a result of the
      marker and the encapsulation. Dosimetric measurements were performed using LiF
      thermoluminescent dosimeters (1 mm3) in solid water phantoms (WT1). Measured data
      were compared to Monte Carlo simulated data in solid water using the MCNP code,
      version 4C. Updated cross sections [Med. Phys. 30, 701-711 (2003)] were used. As
      the measured and calculated data were in agreement, Monte Carlo calculations were
      then performed in liquid water to obtain relevant dosimetric data as required by
      TG-43U1 recommendations. Comparison of the results with previous studies of
      OptiSeed103 [Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311
      321 (2005)], and of InterSource103 [Appl. Radiat. Isot. 57, 805-811 (2002)]
      showed very good agreement for the dose rate constant and for the radial dose
      function. With respect to the anisotropy function, the relative dose (anisotropy
      value relative to 90 degrees) from the polymer seed at a distance of 3 cm was
      close to unity (105%) at 0 degrees, whereas the relative values for the
      OptiSeed103 with a gold marker and the titanium-encapsulated InterSource103 seed
      decreased to 70% and 40%, respectively. The interseed effect from one seed was
      negligible and in the order of calculation uncertainty, making calculation of the
      dose rate distribution of the studied seeds, according to TG43U1 recommendations,
      more accurate and closer to reality. This feasibility study shows that due to the
      low energy of palladium-103, the negligible interseed effect and the reduced
      artifacts in postimplant medical imaging, this experimental plastic seed would be
      a good source for breast brachytherapy. This feasibility study was carried out in
      collaboration with IBt and will be continued with a study of its visibility in
      different tissues.

PMID- 19175141
TI  - Evaluation of a commercial biologically based IMRT treatment planning system.
AB  - A new inverse treatment planning system (TPS) for external beam radiation therapy
      with high energy photons is commercially available that utilizes both dose-volume
      based cost functions and a selection of cost functions which are based on
      biological models. The purpose of this work is to evaluate quality of intensity
      modulated radiation therapy (IMRT) plans resulting from the use of biological
      cost functions in comparison to plans designed using a traditional TPS employing
      dose-volume-based optimization. Treatment planning was performed independently at
      two institutions. For six cancer patients, including head and neck (one case from
      each institution), prostate, brain, liver, and rectal cases, segmental multileaf
      collimator IMRT plans were designed using biological cost functions and compared
      with clinically used dose-based plans for the same patients. Dose-volume
      histograms and dosimetric indices, such as minimum, maximum, and mean dose, were
      extracted and compared between the two types of treatment plans. Comparisons of
      the generalized equivalent uniform dose (EUD), a previously proposed plan quality
      index (fEUD), target conformity and heterogeneity indices, and the number of
      segments and monitor units were also performed. The most prominent feature of the
      biologically based plans was better sparing of organs at risk (OARs). When all
      plans from both institutions were combined, the biologically based plans resulted
      in smaller EUD values for 26 out of 33 OARs by an average of 5.6 Gy (range 0.24
      to 15 Gy). Owing to more efficient beam segmentation and leaf sequencing tools
      implemented in the biologically based TPS compared to the dose-based TPS, an
      estimated treatment delivery time was shorter in most (five out of six) cases
      with some plans showing up to 50% reduction. The biologically based plans were
      generally characterized by a smaller conformity index, but greater heterogeneity
      index compared to the dose-based plans. Overall, compared to plans based on dose
      volume optimization, plans with equivalent target coverage obtained using the
      biologically based TPS demonstrate improved dose distributions for the majority
      of normal structures.

PMID- 19175142
TI  - Dosimetric characterization of a 131Cs brachytherapy source by thermoluminescence
      dosimetry in liquid water.
AB  - Dosimetry measurements of a 131Cs brachytherapy source have been performed in
      liquid water employing thermoluminescence dosimeters. A search of the literature
      reveals that this is the first time a complete set of dosimetric parameters for a
      brachytherapy "seed" source has been measured in liquid water. This method avoids
      the medium correction uncertainties introduced by the use of water-equivalent
      plastic phantoms. To assure confidence in the results, four different sources
      were employed for each parameter measured, and measurements were performed
      multiple times. The measured dosimetric parameters presented here are based on
      the AAPM Task Group 43 formalism. The dose-rate constant measured in liquid water
      was (1.063 +/- 0.023) cGy h(-1) U(-1) and was based on the air-kerma strength
      standard for this source established by the National Institute of Standards and
      Technology. Measured values for the 2D anisotropy function and the radial dose
      function are presented.

PMID- 19175137
TI  - Anniversary paper: History and status of CAD and quantitative image analysis: the
      role of Medical Physics and AAPM.
AB  - The roles of physicists in medical imaging have expanded over the years, from the
      study of imaging systems (sources and detectors) and dose to the assessment of
      image quality and perception, the development of image processing techniques, and
      the development of image analysis methods to assist in detection and diagnosis.
      The latter is a natural extension of medical physicists' goals in developing
      imaging techniques to help physicians acquire diagnostic information and improve
      clinical decisions. Studies indicate that radiologists do not detect all
      abnormalities on images that are visible on retrospective review, and they do not
      always correctly characterize abnormalities that are found. Since the 1950s, the
      potential use of computers had been considered for analysis of radiographic
      abnormalities. In the mid-1980s, however, medical physicists and radiologists
      began major research efforts for computer-aided detection or computer-aided
      diagnosis (CAD), that is, using the computer output as an aid to radiologists-as
      opposed to a completely automatic computer interpretation-focusing initially on
      methods for the detection of lesions on chest radiographs and mammograms. Since
      then, extensive investigations of computerized image analysis for detection or
      diagnosis of abnormalities in a variety of 2D and 3D medical images have been
      conducted. The growth of CAD over the past 20 years has been tremendous-from the
      early days of time-consuming film digitization and CPU-intensive computations on
      a limited number of cases to its current status in which developed CAD approaches
      are evaluated rigorously on large clinically relevant databases. CAD research by
      medical physicists includes many aspects-collecting relevant normal and
      pathological cases; developing computer algorithms appropriate for the medical
      interpretation task including those for segmentation, feature extraction, and
      classifier design; developing methodology for assessing CAD performance;
      validating the algorithms using appropriate cases to measure performance and
      robustness; conducting observer studies with which to evaluate radiologists in
      the diagnostic task without and with the use of the computer aid; and ultimately
      assessing performance with a clinical trial. Medical physicists also have an
      important role in quantitative imaging, by validating the quantitative integrity
      of scanners and developing imaging techniques, and image analysis tools that
      extract quantitative data in a more accurate and automated fashion. As imaging
      systems become more complex and the need for better quantitative information from
      images grows, the future includes the combined research efforts from physicists
      working in CAD with those working on quantitative imaging systems to readily
      yield information on morphology, function, molecular structure, and more-from
      animal imaging research to clinical patient care. A historical review of CAD and
      a discussion of challenges for the future are presented here, along with the
      extension to quantitative image analysis.

PMID- 19175143
TI  - Comparison of two-dimensional and three-dimensional iterative watershed
      segmentation methods in hepatic tumor volumetrics.
AB  - In this work the authors compare the accuracy of two-dimensional (2D) and three
      dimensional (3D) implementations of a computer-aided image segmentation method to
      that of physician observers (using manual outlining) for volume measurements of
      liver tumors visualized with diagnostic contrast-enhanced and PET/CT-based non
      contrast-enhanced (PET-CT) CT scans. The method assessed is a hybridization of
      the watershed method using observer-set markers with a gradient vector flow
      approach. This method is known as the iterative watershed segmentation (IWS)
      method. Initial assessments are performed using software phantoms that model a
      range of tumor shapes, noise levels, and noise qualities. IWS is then applied to
      CT image sets of patients with identified hepatic tumors and compared to the
      physicians' manual outlines on the same tumors. The repeatability of the
      physicians' measurements is also assessed. IWS utilizes multiple levels of
      segmentation performed with the use of "fuzzy regions" that could be considered
      part of a selected tumor. In phantom studies, the outermost volume outline for
      level 1 (called level 1_1 consisting of inner region plus fuzzy region) was
      generally the most accurate. For in vivo studies, the level 1_1 and the second
      outermost outline for level 2 (called level 2_2 consisting of inner region plus
      two fuzzy regions) typically had the smallest percent error values when compared
      to physician observer volume estimates. Our data indicate that allowing the
      operator to choose the "best result" level iteration outline from all generated
      outlines would likely give the more accurate volume for a given tumor rather than
      automatically choosing a particular level iteration outline. The preliminary in
      vivo results indicate that 2D-IWS is likely to be more accurate than 3D-IWS in
      relation to the observer volume estimates.

PMID- 19175144
TI  - Image reconstruction and image quality evaluation for a dual source CT scanner.
AB  - The authors present and evaluate concepts for image reconstruction in dual source
      CT (DSCT). They describe both standard spiral (helical) DSCT image reconstruction
      and electrocardiogram (ECG)-synchronized image reconstruction. For a compact
      mechanical design of the DSCT, one detector (A) can cover the full scan field of
      view, while the other detector (B) has to be restricted to a smaller, central
      field of view. The authors develop an algorithm for scan data completion,
      extrapolating truncated data of detector (B) by using data of detector (A). They
      propose a unified framework for convolution and simultaneous 3D backprojection of
      both (A) and (B) data, with similar treatment of standard spiral, ECG-gated
      spiral, and sequential (axial) scan data. In ECG-synchronized image
      reconstruction, a flexible scan data range per measurement system can be used to
      trade off temporal resolution for reduced image noise. Both data extrapolation
      and image reconstruction are evaluated by means of computer simulated data of
      anthropomorphic phantoms, by phantom measurements and patient studies. The
      authors show that a consistent filter direction along the spiral tangent on both
      detectors is essential to reduce cone-beam artifacts, requiring truncation of the
      extrapolated (B) data after convolution in standard spiral scans. Reconstructions
      of an anthropomorphic thorax phantom demonstrate good image quality and dose
      accumulation as theoretically expected for simultaneous 3D backprojection of the
      filtered (A) data and the truncated filtered (B) data into the same 3D image
      volume. In ECG-gated spiral modes, spiral slice sensitivity profiles (SSPs) show
      only minor dependence on the patient's heart rate if the spiral pitch is properly
      adapted. Measurements with a thin gold plate phantom result in effective slice
      widths (full width at half maximum of the SSP) of 0.63-0.69 mm for the nominal
      0.6 mm slice and 0.82-0.87 mm for the nominal 0.75 mm slice. The visually
      determined through-plane (z axis) spatial resolution in a bar pattern phantom is
      0.33-0.36 mm for the nominal 0.6 mm slice and 0.45 mm for the nominal 0.75 mm
      slice, again almost independent of the patient's heart rate. The authors verify
      the theoretically expected temporal resolution of 83 ms at 330 ms gantry rotation
      time by blur free images of a moving coronary artery phantom with 90 ms rest
      phase and demonstrate image noise reduction as predicted for increased
      reconstruction data ranges per measurement system. Finally, they show that the
      smoothness of the transition between image stacks acquired in different cardiac
      cycles can be efficiently controlled with the proposed approach for ECG
      synchronized image reconstruction.

PMID- 19175145
TI  - A new weighting function to achieve high temporal resolution in circular cone
      beam CT with shifted detectors.
AB  - The size of the field of measurement (FOM) in computed tomography is limited by
      the size of the x-ray detector. In general, the detector is mounted symmetrically
      with respect to the rotation axis such that the transaxial FOM diameter
      approximately equals the lateral dimensions of the detector when being
      demagnified to the isocenter. To enlarge the FOM one may laterally shift the
      detector by up to 50% of its size. Well-known weighting functions must then be
      applied to the raw data prior to convolution and backprojection. In this case, a
      full scan or a scan with more than 360 degrees angular coverage is required to
      obtain complete data. However, there is a small region, the inner FOM, that is
      covered redundantly and where a partial scan reconstruction may be sufficient. A
      new weighting function is proposed that allows one to reconstruct partial scans
      in that inner FOM while it reconstructs full scan or overscan data for the outer
      FOM, which is the part that contains no redundancies. The presented shifted
      detector partial scan algorithm achieves a high temporal resolution in the inner
      FOM while maintaining truncation-free images for the outer part. The partial scan
      window can be arbitrarily shifted in the angular direction, what corresponds to
      shifting the temporal window of the data shown in the inner FOM. This feature
      allows for the reconstruction of dynamic CT data with high temporal resolution.
      The approach presented here is evaluated using simulated and measured data for a
      dual source micro-CT scanner with rotating gantry.

PMID- 19175147
TI  - Multiphasic contrast injection for improved precision of parameter estimates in
      functional CT.
AB  - Contrast injection protocol is known to affect the estimation of kinetic
      parameters in functional CT. A novel method is proposed to maximize the precision
      of parameter estimates by modulating the contrast injection scheme. The method
      models the intravenous contrast bolus to be dispersed by a "patient function" to
      give rise to the arterial input function, which, in turn, carries the contrast
      agent to tissue leading to contrast enhancement. The covariance matrix analysis
      was applied to calculate the uncertainty of parameter estimates as the
      coefficients of variation (CV) in the adiabatic tissue homogeneity (ATH), two
      compartment, and the modified Kety model in which tumor pathophysiology is
      modeled. An optimization scheme was used to determine the optimal injection
      protocol which would minimize the CV of a particular kinetic parameter. For
      clinical utility, a recommended injection protocol was suggested from a
      statistical analysis with the optimal injection protocols obtained from the first
      group of 12 patients with cervix cancer. The efficacy of the recommended
      injection protocol was tested with a second group of 12 patients. In addition,
      the robustness of the recommended injection protocol to longitudinal study has
      been investigated in the presence of variations in arterial input function and
      tumor pathophysiology. Based on the data of the second group of patients, and
      using the ATH model, the recommended biphasic injection of two boluses improves
      the precision in the estimation of blood flow and mean transit time (MTT), by
      36.9% and 38.4%, respectively, compared to the standard uniphasic injection
      protocol in the CV. However, measurement of the permeability surface area product
      and extravascular extracellular space volume favors a single fast bolus of the
      same contrast amount. The two-compartment model and the modified Kety model also
      benefited from the single fast bolus. The effect of variation in the arterial
      input function and tumor pathophysiology on the applicability of the recommended
      injection was also investigated. Based on computer simulation for a range of
      variations in the arterial input function and pathophysiology, the recommended
      biphasic injection was found to improve the precision in blood flow and MTT
      estimates by 31.4% and 36.5% on average, respectively, compared to the uniphasic
      injection.

PMID- 19175146
TI  - Truncation correction for oblique filtering lines.
AB  - State-of-the-art filtered backprojection (FBP) algorithms often define the
      filtering operation to be performed along oblique filtering lines in the
      detector. A limited scan field of view leads to the truncation of those filtering
      lines, which causes artifacts in the final reconstructed volume. In contrast to
      the case where filtering is performed solely along the detector rows, no methods
      are available for the case of oblique filtering lines. In this work, the authors
      present two novel truncation correction methods which effectively handle data
      truncation in this case. Method 1 (basic approach) handles data truncation in two
      successive preprocessing steps by applying a hybrid data extrapolation method,
      which is a combination of a water cylinder extrapolation and a Gaussian
      extrapolation. It is independent of any specific reconstruction algorithm. Method
      2 (kink approach) uses similar concepts for data extrapolation as the basic
      approach but needs to be integrated into the reconstruction algorithm.
      Experiments are presented from simulated data of the FORBILD head phantom,
      acquired along a partial-circle-plus-arc trajectory. The theoretically exact M
      line algorithm is used for reconstruction. Although the discussion is focused on
      theoretically exact algorithms, the proposed truncation correction methods can be
      applied to any FBP algorithm that exposes oblique filtering lines.

PMID- 19175148
TI  - Characterization of a novel anthropomorphic plastinated lung phantom.
AB  - Phantoms are widely used during the development of new imaging systems and
      algorithms. For development and optimization of new imaging systems such as
      tomosynthesis, where conventional image quality metrics may not be applicable, a
      realistic phantom that can be used across imaging systems is desirable. A novel
      anthropomorphic lung phantom was developed by plastination of an actual pig lung.
      The plastinated phantom is characterized and compared with reference to in vivo
      images of the same tissue prior to plastination using high resolution 3D CT. The
      phantom is stable over time and preserves the anatomical features and relative
      locations of the in vivo sample. The volumes for different tissue types in the
      phantom are comparable to the in vivo counterparts, and CT numbers for different
      tissue types fall within a clinically useful range. Based on the measured CT
      numbers, the phantom cardiac tissue experienced a 92% decrease in bulk density
      and the phantom pulmonary tissue experienced a 78% decrease in bulk density
      compared to their in vivo counterparts. By-products in the phantom from the room
      temperature vulcanizing silicone and plastination process are also identified. A
      second generation phantom, which eliminates most of the by-products, is
      presented. Such anthropomorphic phantoms can be used to evaluate a wide range of
      novel imaging systems.

PMID- 19175149
TI  - Objective assessment of deformable image registration in radiotherapy: a multi
      institution study.
AB  - The looming potential of deformable alignment tools to play an integral role in
      adaptive radiotherapy suggests a need for objective assessment of these complex
      algorithms. Previous studies in this area are based on the ability of alignment
      to reproduce analytically generated deformations applied to sample image data, or
      use of contours or bifurcations as ground truth for evaluation of alignment
      accuracy. In this study, a deformable phantom was embedded with 48 small plastic
      markers, placed in regions varying from high contrast to roughly uniform regional
      intensity, and small to large regional discontinuities in movement. CT volumes of
      this phantom were acquired at different deformation states. After manual
      localization of marker coordinates, images were edited to remove the markers. The
      resulting image volumes were sent to five collaborating institutions, each of
      which has developed previously published deformable alignment tools routinely in
      use. Alignments were done, and applied to the list of reference coordinates at
      the inhale state. The transformed coordinates were compared to the actual marker
      locations at exhale. A total of eight alignment techniques were tested from the
      six institutions. All algorithms performed generally well, as compared to
      previous publications. Average errors in predicted location ranged from 1.5 to
      3.9 mm, depending on technique. No algorithm was uniformly accurate across all
      regions of the phantom, with maximum errors ranging from 5.1 to 15.4 mm. Larger
      errors were seen in regions near significant shape changes, as well as areas with
      uniform contrast but large local motion discontinuity. Although reasonable
      accuracy was achieved overall, the variation of error in different regions
      suggests caution in globally accepting the results from deformable alignment.

PMID- 19175151
TI  - Note to readers of Medical Physics.

PMID- 19175150
TI  - Comment on "Quantifying the interplay effect in prostate IMRT delivery using a
      convolution-based method" [Med. Phys. 35, 1703-1710 (2008)].

PMID- 19175152
TI  - [Pay more attention to appropriate application of fundus imaging technologies].
AB  - There are several methods of fundus examination in clinical practice. Each method
      has its own characteristic and should not replace for each other. Though the
      combination of these methods has been conformed to improve the level of diagnosis
      and therapy for the fundus diseases, some ophthalmologists are puzzled how to
      choose the methods and how to explain the results of each examination. Some
      suggestions are provided to solve these problems.

PMID- 19175153
TI  - [Paying attention to the application of examining fundus autofluorescence in the
      diagnosis of fundus disease].
AB  - Nowadays there are many methods to check out the fundus diseases, including
      fundus fluorescence angiography (FFA), indocyanine green angiography (ICGA),
      optical coherence tomography (OCT) and so on, which have already been used widely
      all over the world. However, the value of fundus autofluorescence angiography
      (FAF) in diagnosing fundus diseases, which has been paid much attention worldwide
      over the past ten years, does not cause enough attention in our nation. The
      reasons are that we are deficient about the knowledge of the mechanism of fundus
      autofluorescence produced, and its meaning of the clinical application of fundus
      autofluorescence and so on. This passage aims to base on demonstrating the
      problems above, and emphasize that fundus autofluorescence is as a promising, non
      invasive imaging method and has high value in the clinical application,
      especially in the diagnosing the fundus diseases, monitoring its development and
      therapeutic results. Therefore, it needs to be given high attention,
      dissemination and spread in our nation.

PMID- 19175154
TI  - [Risk factors and prognosis of peripheral retinal breaks complicating pars plana
      vitrectomy].
AB  - OBJECTIVE: To assess the risk factors and prognosis of peripheral retinal breaks
      complicating pars plana vitrectomy. METHODS: Retrospective observational case
      series. Four hundred and four consecutive vitrectomies performed on eyes without
      preexisting retinal breaks or retinal detachments were retrospectively reviewed.
      Cases with peripheral retinal breaks found during or after the vitrectomy were
      recorded and analyzed. RESULTS: Of the 404 vitrectomies, 32 eyes had 55
      iatrogenic peripheral retinal breaks with an average incidence of 7.9%.
      Peripheral retinal breaks were most common in cases with branch retinal vein
      occlusion (BRVO) (13.3%) and less common in proliferative diabetic retinopathy
      (PDR) (3.7%) (chi2 =9.18, P<0.01). Of the 55 breaks, 51 (92.7%) occurred around
      the sclerotomy sites, and 29 (52.7%) in the quadrant corresponding to the
      predominant hand of the surgeon. Cases with breaks detected during surgery had a
      better outcome of retinal reattachment as compared with cases identified
      postoperatively. CONCLUSIONS: Peripheral retinal breaks complicating pars plana
      vitrectomy is mainly sclerotomy-related and is more common in cases with BRVO
      than in cases with PDR. Early detection during surgery tends to have a better
      outcome.

PMID- 19175155
TI  - [Analysis of clinical features of choroidal neovascularization].
AB  - OBJECTIVE: To investigate the clinical features of choroidal neovascularization
      (CNV) in different classifications. METHODS: In this retrospective case series,
      393 eyes of 312 patients with CNV between May 2005 and March 2007 in our
      department was classified based on their etiology, location, fundus fluorescein
      angiography (FFA) and indocyanine green angiography (ICGA) findings. RESULTS: The
      relative frequency of various causes in CNV was as follows: there were 153 cases
      (49.04%) from age-related macular degeneration (AMD) , 94 cases (30.13%) from
      idiopathic CNV, 37 cases (11.86%) from pathologic myopia, 15 cases (4.81%) from
      inflammatory disorders, 7 cases (2.24%) from polypoidal choroidal vasculopathy
      (PCV), 3 cases (0.96%) from angioid streaks and 1 case (0.32%) from either
      hereditary disease or trauma or tumor, respectively. The majority cases from AMD
      was male (64.71%), whereas most from pathologic myopia, idiopathic CNV and
      inflammatory disorders were female (78.38%, 73.40%, 73.33%). The age range of the
      cases from AMD was 49-95 years (68.73 +/- 8.31), and 98.04% of them were at least
      50 years old. Patients with idiopathic CNV aged 13-43 years old (29.86 +/- 6.45),
      and 84.04% of them were between 20 and 40 years old. The sex (chi2 = 57.17,
      P<0.05) and age (F=172.57, P< 0.05) had significant difference in each
      etiological group. FFA showed that CNV in 43.48% from AMD and 66.67% from PCV
      were occult and non-classic. CNV in 91.67% from pathologic myopia, 76.19% from
      inflammatory disorders and 95.00% from idiopathic CNV was classic. In each group,
      most of the CNV was subfoveal type (58.00%-100.00%), followed by juxtafoveal type
      (0%-35.00%). In the ICGA of 54 eyes with AMD, 11 eyes (20.37%) were occult CNV
      (plaque, spot and mixed CNV), 17 eyes (31.48%) were CNV fibrosis. CNV was active
      in most cases. The frequency of active and inactive CNV in AMD was approximately
      61.11% and 37.04%, respectively, no lesions were noted in 1 eye (1.85%) in ICGA.
      CONCLUSIONS: The clinical characteristics and frequency of various types of CNV
      are different due to different causes. Classification of CNV based on its
      etiology, FFA and ICGA findings, location, and activity in detail is important
      for the diagnosis, treatment and prognosis judgment in CNV.

PMID- 19175156
TI  - [Follow-up study of traumatic macular hole].
AB  - OBJECTIVE: To investigate the natural course and visual outcomes of traumatic
      macular hole. METHODS: This was a case series observation study. Patients with
      traumatic macular hole were followed-up for 3 months or longer from August 2004
      to December 2007. Examinations included best-corrected visual acuity, fundus
      photography and optical coherence tomography. RESULTS: In a consecutive case
      series of 48 patients (48 eyes) with traumatic macular hole, 28 eyes of 28
      patients were followed for more than 3 months, with an average of 14 months. Of
      the 28 patients (28 eyes), 16 patients (16 eyes, 57.1%) had traumatic choroidal
      or retinal changes surrounding the macular hole. The size of the macular holes
      changed in 16 (16 eyes) of 28 patients (28 eyes) during the follow-up period.
      Macular hole enlarged in 9 (9 eyes) of the 28 patients (28 eyes), became smaller
      in 1 patient (1 eyes), and closed spontaneously in 3 patients (3 eyes). Macular
      hole closure occurred 4.5, 3.5, and 1 month after the onset of macular hole,
      respectively. The closure rate was 10.7% (3/28).Visual acuity improved in all the
      patients with macular hole closure. Final best-corrected visual acuity ranged
      from 0.5 to 0.7. Retinal detachment occurred in 2 patients (2 eyes) and the
      occurrence rate was 4.2% (2/48). The retina re-attached and visual acuity
      improved in these 2 cases (2 eyes) after surgical treatment. CONCLUSIONS: Visual
      acuity remains stable or improves in most patients with traumatic macular hole.
      Spontaneous closure occurs in some cases 4 to 5 months after the onset of the
      macular hole with good visual recovery. Retinal detachment is rare in traumatic
      macular hole.

PMID- 19175157
TI  - [Combination facula photodynamic therapy for circumscribed choroidal hemangioma].
AB  - OBJECTIVE: To assess the clinical effect of combination facula photodynamic
      therapy (PDT) on patients with circumscribed choroidal hemangioma. METHODS: It
      was a retrospective case series. Ten cases of circumscribed choroidal hemangioma
      were diagnosed by ophthalmoscopy, fundus fluorescein angiography and B-scanning
      ultrasound examination. Clinical data of these cases were retrospectively
      analyzed. All of these patients had undergone combination facula PDT. The best
      corrected visual acuity before PDT was FC to 0.3. The maximum diameter of the
      tumor was 5.5-9.9 mm and averaged 6-8 mm. The maximum thickness of the tumor was
      1.1-3.8 mm and averaged 2.7 mm. Four patients suffered from retinal detachment
      The intravenous injection of visudyne (6 mg/m2) was performed in 10 minutes. Five
      minutes later, laser irradiation (wave length 689 nm) was performed with the
      parameters of 50 J/cm2, 83 s, and 2 to 3 spots. The follow-up period was 3.0 to
      15.0 months (mean 8.5 months). RESULTS: The visual acuity in the last examination
      after treatment was FC-1.0, which was 2-line increased in 7 patients and was
      steady in 3 patients. B-scanning ultrasound examination showed that the
      hemangioma was undetectable in 2 patients, and in the other 8 patients,the
      hemangioma had the diameter of 4.2 to 8.3 mm (average 6.4 mm) and the thickness
      was 0.5 to 2.7 mm (average 1.9 mm). Retina detachment disappeared in 2 patients
      CONCLUSIONS: Combination facula PDT may lead to the shrinking of choroidal
      hemangioma, disappearance of subretinal fluid, reattachment of retina and the
      increase or saving of the visual acuity. It is a effective and safe treatment for
      the macular circumscribed choroidal hemangioma.

PMID- 19175158
TI  - [Observation on morphology and function of macular in pathologic myopia].
AB  - OBJECTIVE: To observe the morphology and function of the macular in pathologic
      myopia by the combination of the fundus examination, optic coherence tomography
      and multifocal electroretinogram (mERG). To analyze the relationships among
      macular function, ocular axis length, refraction and corrected visual acuity.
      METHODS: Case series including 36 eyes of 31 consecutive pathologic myopia cases,
      which were chosen from Tongren Eye Center from February to April 2006 and divided
      into two groups according to ocular axis length:group A, composed of 12 eyes from
      10 cases (axis length > or = 30.00 mm) and group B, composed of 24 eyes from 21
      cases (<30.00 mm). Manifest refraction, A and B scan, fundus examination, OCT
      scan for the macular area, the measurement of the thickness of the retinal
      neuroepithelial layer and mERG were carried out for each eyes. The results were
      further analyzed by comparing the ocular axis length, diopter of myopia,
      corrected visual acuity, results of the OCT study and mERG. Relationships among
      the macular function, ocular axis length, refraction and corrected visual acuity
      were also analyzed. RESULTS: The mean ocular axis length, diopter of myopia,
      corrected visual acuity of group A were (31.77 +/- 1.27) mm, (-22.92 +/- 7.10) D
      and (0.31 +/- 0.25), respectively. The mean ocular axis length, diopter of
      myopia, corrected visual acuity of group B were (28.64 +/- 1.17) mm, (-14.03 +/-
      5.37) D, (0.55 +/- 0.35 ), respectively. Statistically significant difference was
      shown between these two groups (t = -2.28, P<0.05). The thickness of neural
      retina of area 1 to 5 in group A was smaller than that of group B, and
      significant differences exists between these two groups (P = 0.016, 0.032, 0.048,
      0.009, 0.002). There were statistical differences in amplitude densities of P1
      waves in central macular, super-temporal quadrants, super-nasal quadrants and
      infer-nasal quadrants between these two groups (t = 3.63, 2.71, 2.21, 2.32, 2.64,
      P<0.05). Amplitude densities of P1 waves showed negative correlation to ocular
      axis length (r = - 0.498, P<0.01) and positive correlation to corrected visual
      acuity (r = 0.468, P<0.01). Ocular axis length showed positive correlation to
      diopter of myopia (r = 0.800, P<0.01) and negative correlation to corrected
      visual acuity (r = -0.605, P<0.01). Diopter of myopia was negatively correlated
      to corrected visual acuity (r = -0.616, P< 0.01). CONCLUSIONS: Visual function
      loss in pathologic myopia is correlated with the increase of diopter of myopia,
      decrease of corrected visual acuity, increased macular disease and decreased
      macular function and extensive elongation of ocular axis in pathologic myopia. A
      combination of fundus examination, OCT scan and mERG may contribute to the
      earlier detection and monitoring of progression of the macular abnormality.

PMID- 19175159
TI  - [Endoplasmic reticulum stress participates in the cell apoptosis process in
      experimental retinal detachment].
AB  - OBJECTIVE: To determine whether the endoplasmic reticulum stress participates
      into the apoptosis process of the retina during experimental retinal detachment
      by detecting the level of mRNA and protein of the GADD153, the marker of
      endoplasmic reticulum stress. METHODS: Completely random design is applied.
      Experimental retinal detachment was created in the left eyes of 77 wistar rats by
      injecting hyaluronic acid into the subretinal space. Rats were sacrificed at 1/2
      d, 1 d, 2 d, 4 d, 8 d, 16 d and 32 d after creation of retinal detachment.
      Apoptosis of retinal cells was detected by TdT-mediated fluorescein-16-dUTP nick
      end labeling (TUNEL) assay. GADD153 mRNA expression in the retina was determined
      using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).
      The GADD153 protein expression was determined using western blotting. Retinal
      sections were studied by immunofluorescence labeling and confocal microscopy. The
      SPSS 10.0 software was applied to analyze data; Kruskal wallis test was applied
      to analyze the data about the apoptotic rate of retinal cells and the expression
      of GADD153 mRNA; One-way ANOVA test was applied to analyze the data about
      expression of GADD153 protein. P < 0.05 represents statistically significant
      difference. RESULTS: TUNEL positive staining cells were mainly presented in
      photoreceptor cell layer, peaked at 24 days and markedly decreased at 8 days
      after retinal detachment. The difference of apoptotic retinal cell rate between
      groups is significant (chi2 = 22.423, P < 0.05); The expression of retinal
      GADD153 mRNA was significantly increased at 1/2 d, 1 d, 2 d, 4 d after retinal
      detachment (chi2 = 27.223, P < 0.05); The expression of retinal GADD153 protein
      was significantly increased at these days (F = 16.052, P < 0.05). GADD153
      positive cells were located in the photoreceptor cell layer. CONCLUSIONS:
      GADD153, the maker of endoplasmic reticulum stress mediated apoptosis, is
      activated and over-expressed, associated with the occurrence of apoptosis during
      retinal detachment. Endoplasmic reticulum stress participates into the apoptosis
      process during retinal detachment.

PMID- 19175160
TI  - [Endoplasmic reticulum stress proteins are activated in rd retinal degeneration].
AB  - OBJECTIVE: To investigate the expression of endoplasmic reticulum (ER) stress
      proteins in photoreceptor apoptosis in rd mouse (Pde6bRd1/Rd1). METHODS:
      Photoreceptor apoptosis in rd mouse was detected by terminal dUTP transferase
      nick end labeling (TUNEL). The protein expression of ER stress sensors including
      glucose-regulated protein-78 (GRP78/BiP), caspase-12, phospho-eukaryotic
      initiation factor 2alpha (eIF2alpha) and phospho-pancreatic ER kinase (PERK) was
      examined by immunofluorescence and Western Blot analysis. RESULTS: Accompanying
      photoreceptor apoptosis in rd mouse, protein expression of GRP78/BiP, caspase-12,
      phospho-eIF2alpha and phospho-PERK was up-regulated in a time dependent manner.
      The up-regulation of these proteins coincided with or preceded the photoreceptor
      apoptosis. At the peak of their expression, they were mainly located in the
      photoreceptor inner segment and/or outer nuclear layer (ONL). CONCLUSION:
      Activation of ER stress proteins appears to play an important role in rd retinal
      degeneration. Therefore endoplasmic reticulum stress modulators could be a strong
      candidate as a therapeutic agent in the treatment of these diseases.

PMID- 19175161
TI  - [The preliminary study of Phosphomannopentaose sulfate (PI-88) on the
      experimental choroidal neovascularization].
AB  - OBJECTIVE: To probe the intervention and mechanism of the inhibitor of heparanase
      (PI-88) on the experimental CNV model . METHODS: Experimental CNV was induced by
      laser photocoagulation in 29 mail (Brown Norway) BN rats (647 nm wave length
      Krypton laser, 360 mW power, 50 microm spot size, 0.05 second duration), and
      randomly divided into vacant control group, physiologic saline control group,
      preventive group and treated group, another 3 rats were acted as normal group, 15
      days continuous intraperitoneal injection of PI-88 (25 mg kg(-1) d(-1) was
      administrated in preventive group (PI-88 was administered the same day as
      photocoagulation) and treated group (PI-88 was administered 1 week after
      photocoagulation when CNV had been formed), for the physiologic saline control
      group, PI-88 was replaced by physiologic saline. To comprehensively evaluate the
      effect of PI-88 on the CNV by the quantitation of CNV area marked by FITC-dextran
      in choroid-sclera flat mounts, fluorescence fundus angiography and
      histopathology; the changes of HPA expression were surveyed by western blot and
      immunohistochemistry. RESULTS: CNV area of preventive group and treated group
      decreased 52.1% and 53.8% respectively at the time point of 3 weeks after
      photocoagulation; the relative thickness of CNV membrane in eyes of treated group
      had been decreased 46% as that of control group by histopathology; CNV
      occurrenced 1 week after photocoagulation both in the control group and
      preventive group, while the fluorescein leakage of the preventive group had been
      inhibited significantly; 3 weeks after photocoagulation, there had been 7 days
      discontinuation for the prevent group, the fluorescein leakage did not enhanced,
      while there had been 15 days continuous administration for the treated group, the
      fluorescein leakage had been decreased significantly compared to the time point
      of 2 week; western blot showed that the relative expressed levels of HPA protein
      in both preventive and treated group decreased; HPA displayed distribution at the
      leading edge of CNV membrane migrating toward inner retina and the vascular
      tissue by immunohistochemistry, the expression of HPA was inhibited significantly
      in treated group. CONCLUSION: PI-88 may not only prevent CNV in certain degree,
      but also make it partially subsidize for the existed CNV, and the effect is
      associated with the inhibition of HPA production.

PMID- 19175162
TI  - [Clinical studies on Q-factor guided LASIK for the correction of myopic
      astigmatism].
AB  - OBJECTIVE: To compare the results of the Q-factor guided LASIK with the
      conventional LASIK for the correction of myopic astigmatism. METHODS: Forty-three
      eyes underwent Q-factor guided LASIK and 41 eyes were received conventional
      LASIK. The patients were followed up for more than 3 months . Examinations
      included refraction, distance and near vision, noncontact tonometer, topography
      (provide Q value), aberrometer, ultrasonic pachymetry, contrast sensitivity
      function. RESULTS: At 3 months, 97.67% of Q-factor guided LASIK eyes attained
      UNCVA 1.0 or better and 97.56% eyes in the control group. The mean postoperative
      SE for Q-factor guided LASIK group was (-0.19 +/- 0.20) diopters (D) at 3 months
      and (- 0.17 +/- 0.17) diopters (D) in conventional LASIK group. The postoperative
      Q value of Q-factor guided LASIK was (0.50 +/- 0.28) and (0.82 +/- 0.40) in the
      conventional LASIK group, significant difference was noted between two groups.
      Both Q-factor guided LASIK and conventional LASIK significantly increased
      spherical aberration, the mean RMS of postoperative spherical aberration were (
      0.265 +/- 0.156) microm, (-0.487 +/- 0.159) microm respectively, significant
      difference were noted between two groups at 3 months . Contrast sensitivity was
      reduced at 1 week and restored at 1 month postoperatively in Q-factor guided
      LASIK, while in conventional LASIK it was reduced at 1 week, 1 month and restored
      at 3 months. Corneal topography revealed in Q-factor guided LASIK the diameter of
      effective optical zone (EOZ) was (5.74 +/- 0.22) mm. However postoperative EOZ of
      conventional LASIK was (5.34 +/- 0.29) mm in control group. CONCLUSIONS: Q-factor
      guided LASIK is effective, safe and predictable for correction of myopic
      astigmatism. The postoperative visual quality of Q-factor guided LASIK is better
      than that of conventional LASIK due to its superiority for correction of
      spherical aberration.

PMID- 19175163
TI  - [Reconstruction tissue-engineered corneal epithelium using xenogeneic acellular
      corneal stroma as scaffold].
AB  - OBJECTIVE: To compare two methods for preparing acellular corneal stroma and
      evaluate the possibility of culturing corneal epithelium on xenogeneic acellular
      corneal stroma. METHODS: Experimental study, applying completely randomized
      design method. Dispase followed by Triton-X-100 detergent and sodium chloride SDS
      detergent followed by trypsinase were applied respectively to treat the rabbit
      cornea. The characteristics of corneal stroma and acellular status after
      treatment were examined with slit lamp, optical microscope and transmission
      electron microscope. The rabbit limbal cells were then cultured on the acellular
      porcine Bowman's membrane/stroma. Rabbit corneal epithelium lamella reconstructed
      in vitro and evaluated in morphology, histopathology and immunohisto-chemistry.
      RESULTS: Acellular corneal stroma prepared by two different methods is quite
      similar in morphology, being gray and opaque with visible edema and soft texture.
      Collagen fibers of the stroma were regularly in histopathology and
      ultrastructure. But the one prepared by the NaCl-SDS-Trypsinase method retained a
      amounts of cell debris, while there was none in the other did by Dispase-Triton-X
      100 method. The limbal cells began to shift out at 24 hours after being
      inoculated on xenogeneic acellular corneal stroma, then attached on it, formed a
      confluent monolayer containing normal-appearing in 7 days. The tissue engineering
      corneal epithelium was cryosectioned and characterized immunohistochemically at
      14 days after inoculation. Meanwhile, epithelium associated antigen CK3 in
      endochylema was stained. CONCLUSIONS: Dispase-Triton-X-100 was proved better in
      obtaining acellular corneal stroma. It is possible to reconstruction tissue
      engineered rabbit's corneal epithelium on acellular porcine corneal Bowman's
      membrane/stroma.

PMID- 19175164
TI  - [RNA interference inhibits expression of cyclooxygenase-2 and matrix
      metalloproteinase-2 in rabbit corneal stromal cells].
AB  - OBJECTIVE: To research the effect of short hairpin RNA (shRNA) targeting
      cyclooxygenase-2 (COX-2) on the expression of COX-2 and MMP-2 in rabbit corneal
      stromal cells in vitro. METHODS: It was a experimental study. Rabbit corneal
      stromal cells were cultured in vitro. The transfection efficiency of siRNA
      mediated by HiperFect Transfection Reagent was determined in rabbit corneal
      stromal cells in order to optimize the transfection condition. shRNAs (shRNA
      1,2,3) specific for COX-2 and one negative control nonspecific shRNA were
      designed, then were transfected by HiperFect Transfection Reagent into both
      normal rabbit corneal stromal cells and those which were stimulated by IL-1alpha.
      6, 12, 24, 48, 72 hours after IL-1alpha added, cells were collected for Real-Time
      PCR to detect the gene expression of COX-2 and MMP-2, then the results were
      compared with those of control group. The data of all groups at the same time was
      analyzed by one-factor analysis of variance, and the comparison of any two groups
      was carried out by q-test. RESULTS: The siRNA mediated by HiperFect Transfection
      Reagent can be transfected efficiently into rabbit corneal stromal cells in
      vitro, and the maximum efficiency was 70%-80%. The expression of COX-2 and MMP-2
      mRNA after IL-1alpha stimulated was much higher than that of blank group. shRNA-2
      can significantly inhibit the expression of COX-2 and MMP-2 mRNA in corneal
      stromal cells stimulated with IL-1alpha. The level of COX-2 and MMP-2 was reduced
      83.04% and 73.69% respectively, compared with the expression of single IL-1alpha
      stimulated group, the difference had statistical significance (q = 24.03, P =
      0.00; q = 14.76, P =0.00). The difference of COX-2 mRNA among transfection groups
      of shRNA-1, shRNA-3, negative control shRNA and single IL-1alpha stimulated group
      had no statistical significance (F = 0.02, P =0.99). The difference of MMP-2 mRNA
      among those groups also had no statistical significance (F = 0.02, P = 0.98).
      CONCLUSION: The RNA interference targeting COX-2 can effectively inhibit the
      expression of COX-2 and MMP-2 in IL-1alpha stimulated rabbit corneal stromal
      cells in vitro.

PMID- 19175165
TI  - [Analysis of ophthalmic projects granted by National Natural Science Foundation].
AB  - OBJECTIVE: To understand the status of basic research work in the field of
      ophthalmology by analyzing the projects funded by the National Natural Science
      Foundation of China (NSFC) from the year of 1986 to 2007, and offer as a
      reference to the ophthalmologists and researchers. METHODS: NSFC supported
      ophthalmology projects in the 22 year's period were collected from the database
      of NSFC. The field of funded projects, the research team and their achievements
      were analyzed. RESULTS: There were 228 applicants from 47 home institutions were
      funded in the field of ophthalmology during the past 22 years, 323 projects
      funded with 66.74 million Yuan in total, in which 165 projects were fulfilled
      before the end of 2006. The applied and funded projects mainly focus on six
      different kinds of research area related to retinal diseases, corneal diseases,
      glaucoma, optic nerve diseases, myopia and cataract, and 70% of them were basic
      research in nature. As a brief achievement of 165 fulfilled projects, more than
      610 papers were published in domestic journals, over 140 papers were published in
      Science Citation Index journals, more than 600 people were trained, and over 20
      scientific awards were obtained. CONCLUSION: The number of funded projects and
      achievement of fulfilled projects in the discipline of ophthalmology gradually
      increased over the past two decades, the research fields were concentrated in
      certain diseases. NSFC has played an important role in promoting the development
      of ophthalmology research and bringing up specialists in China. However, clinical
      research, continuously research, transforming from basic research to clinic
      applications and multidisciplinary cross studies should be strengthened.

PMID- 19175166
TI  - [Research advancement of optic nerve injury therapy by transgenic expression
      neurotrophic factors].
AB  - Optic nerve injury is one of factors leading to blindness, and the effective
      therapy is still not available in clinic. The neurotrophic factors (NTF) can
      significantly enhance the survival of retinal ganglion cells (RGC) and the
      regeneration of axonal but showed a short-term effect in vivo. The continue
      expression of NTF by transgenic technology could overcome this disadvantage,
      which may provide a new therapeutic approach for the optic nerve injury. We
      reviewed the articles regarding the research progress of transgenic technology in
      the treatment of optic nerve injure by NTF recently.

PMID- 19175167
TI  - [The main public health issues of earthquake disaster and emergency operation
      strategy].

PMID- 19175168
TI  - [Chinese endemic disease prevalence, prevention and countermeasure].

PMID- 19175169
TI  - [Investigation of anxiety among 402 tent inhabitants in Jiangyou city after the
      5.12 Sichuan earthquake].
AB  - OBJECTIVE: To investigate the prevalence of anxiety among tent inhabitants one
      month after the 5.12 Sichuan earthquake as to formulating intervention
      strategies. METHODS: A stratified random sampling method was adopted. Inclusion
      criteria were: inhabitants, aged above 18 years old, living in tent in 13 relief
      centers of 4 townships in Jiangyou city; and only one person from each
      tent/family could be enrolled in this study. A total of 402 subjects were
      interviewed with Self-rating Anxiety Scale (SAS). SAS scores were compared
      between different groups and symptomatic differences between anxiety and non
      anxiety victims were analyzed by stepwise multiple regression analysis. RESULTS:
      The prevalence of anxiety among tent inhabitants was 22.1% (89/402). A higher
      rate of anxiety was observed in senior age group than in younger age group (F =
      7.03, P < 0.01). Age with > or = 50 years (42.85 +/- 11.15), 40-49 years (41.57
      +/- 10.30), 30-39 years (37.99 +/- 9.66), 18-29 years (36.62 +/- 9.92). Female
      (43.13 +/- 10.45) had a high rate of anxiety than male (36.80 +/- 9.88) (t = 
      6.09, P < 0.01). The most common symptoms were anxiety (79.4%, 319/402), fatigue
      (68.2%, 274/402), phobia (65.7%, 264/402), sleep disorders (65.4%, 263/402),
      unfortunate feelings (65.2% , 262/402), akathisia (59.7%, 240/402), and fear
      (58.2%, 234/402). Stepwise multiple regression analysis revealed that insane
      feelings(t = 5.37, P < 0.01), trembling(t = 5.33, P < 0.01), dyspnea (t = 4.28, P
      < 0.01), unfortunate feelings (t = 3.87, P < 0.01), headache(t = 3.85, P < 0.01),
      facial flushing (t = 3.48, P <0.01), fatigue (t = 3.27, P < 0.01), dizziness (t =
      2.79, P < 0.01), frequent micturition (t = 2.41, P < 0.05), and akathisia (t =
      2.31, P < 0.05) were more frequently experienced in the anxiety victims than non
      anxiety victims. CONCLUSION: Tent inhabitants in the post-earthquake relief
      centers exhibit a higher prevalence of anxiety as compared with the general
      population. Much attention should be paid to elderly, female, and those who have
      developed specific symptoms such as insane feelings, trembling, dyspnea, etc.
      Meanwhile, some intervention measures should be timely taken.

PMID- 19175170
TI  - [A survey of sanitary working status 20 days after the earthquake in Dujiangyan
      municipality].
AB  - OBJECTIVE: To investigate the sanitary working status in the districts for
      locating residents after earthquake in Dujiangyan municipality. METHODS: Some
      immediate measures were taken after the earthquake including water source
      surveillance, restoring immunization system and epidemic surveillance. A
      questionnaire survey was also conducted to collect information in 107 locating
      districts of 18 towns. RESULTS: Generally, the sanitary working status was good.
      Temporary sheds in most districts were Tents (75.70%, 81/107) and simple sheds
      (19.63%, 21/107), and 69.16% (74/107) districts could use water supply and 94.39%
      (101/107) arrange specialized persons to disinfect the environment and kill
      pests. The fly density was 2 per eye-view. The proportions for the correct
      responds to health knowledge, action adopted and attitude of residents were all
      above 90%. According to the epidemic surveillance system and mobile syndrome
      surveillance system in disaster area, there was no increasing trend for the
      incidences of contagious diseases. CONCLUSION: 20 days after earthquake, the
      whole situation of disease prevention in disaster area is stable.

PMID- 19175171
TI  - [Effect of glutathione and sodium selenite on the metabolism of arsenic in mice
      exposed to arsenic through drinking water].
AB  - OBJECTIVE: To explore the effect of glutathione (GSH) and sodium selenite on the
      metabolism of arsenic in the liver, kidney and blood of mice exposed to iAsIII
      through drinking water. METHODS: The mice were randomly divided into control,
      arsenic, GSH and sodium selenite group, respectively. And each group had eight
      mice and the mice were exposed to 50 mg/L arsenite by drinking water for 4 weeks.
      Mice were intraperitoneally injected with GSH (600 mg/kg) and sodium selenite (1
      mg/kg) for seven days from the beginning of the fourth week. At the end of the
      fourth week, liver, kidney and blood were sampled to assess the concentrations of
      inorganic arsenic (iAs), monomethylarsenic acid (MMA), dimethylarsenic acid (DMA)
      by hydride generation trapping by ultra-hypothermia coupled with atomic
      absorption spectrometry. RESULTS: The liver DMA (233.76 +/- 60.63 ng/g)
      concentration in GSH group was significantly higher than the arsenic group
      (218.36 +/- 42.71 ng/g). The concentration of DMA (88.52 +/- 30.86 ng/g) and
      total arsenic (TAs) (162.32 +/- 49.45 ng/g) in blood of GSH group was
      significantly higher than those [(45.32 +/- 12.19 ng/g), (108.51 +/- 18.00 ng/g),
      respectively] of arsenic groups(q values were 3.06, 6.40, 10.72 respectively, P <
      0.05). The primary methylated index (PMI) (0.65 +/- 0.050) and secondary
      methylated index (SMI) (0.55 +/- 0.050) in liver sample of GSH group were
      significantly higher than those (0.58 +/- 0.056, 0.44 +/- 0. 093) in arsenic
      group. In blood samples, the PMI (0.85 +/- 0.066) in GSH group was significantly
      higher than that (0.54 +/- 0.113) in arsenic group (q values were 3.75, 5.26,
      4.21 respectively, P < 0.05). However, no significant difference was identified
      between sodium selenite and arsenic groups in liver, kidney or blood samples. And
      no significant difference was detected in kidney samples among all arsenic
      exposing groups. CONCLUSION: Exogenous GSH could promote the methylated
      metabolism of iAsIII, but sodium selenite showed no significant effects.

PMID- 19175172
TI  - [The effect of selenium on the expression of Fas/FasL in experimental autoimmune
      thyroiditis rats' thyroid with adequate iodine].
AB  - OBJECTIVE: To study the effect of different selenium intake on the expression of
      apoptosis protein Fas/FasL in experimental autoimmune thyroiditis (EAT) rats'
      thyroid with adequate iodine. METHODS: Thirty-two female lewis rats were divided
      stochastically into 4 groups as C group, M group, Se(+) + M group, Se(-) + M
      group, respectively, and pretreated with feedstuffs containing different
      concentrations of selenium (Se(+) + M group 2 mg/kg, C and M group 0.20 mg/kg,
      Se(-) + M group 0.02 mg/kg, respectively) for two weeks, and immunized the rats
      with porcine thyroglobulin (pTg) to establish an EAT model. The thyroid gland was
      sampled, embedded in mineral wax and sliced, and the expression of Fas/FasL was
      measured with immunohistochemistry. RESULTS: Both the expressions of Fas and FasL
      of EAT rats were significantly increased as compared with control group. The
      expression of Fas in rats' thyroid follicular cells with EAT was down-regulated
      as the increased selenium intake (optical density: 0.059 +/- 0.006), the
      expression of Fas of Se(+) + M group (0.036 +/- 0.004) was significantly
      inhibited (q = 11.591, P = 0.000), and expression of Fas was lower in the Se(+) +
      M group than Se(-) + M group (0.050 +/- 0.005) (q = 7.055 , P = 0.000). Effect of
      selenium on FasL was not identified. CONCLUSION: Increasing the intake of
      selenium might decrease the expression of Fas on thyroid follicular cells and
      restrain the development of EAT.

PMID- 19175173
TI  - [Interaction of fluorine, calcium and iodine on weight of rats].
AB  - OBJECTIVE: To study the interaction of fluorine (F), calcium (Ca) and iodine (I)
      on body weight of rats. METHODS: One-month-old Wistar rats were randomly divided
      into 8 groups: moderate concentrations of F, Ca, I (group 1); moderate
      concentrations of F, I and high concentration of Ca (group 2); moderate
      concentrations of Ca, I and high concentration of F (group 3); moderate
      concentration of I and high concentrations of F, Ca (group 4); moderate
      concentrations of F, Ca and low concentration of I (group 5); moderate
      concentration of F,high concentration of Ca and low concentration of I (group 6);
      moderate concentration of Ca, high concentration of F and low concentration of I
      (group 7); high concentrations of F, Ca and low concentration of I (group 8)
      based on 2 x 2 x 2 factorial design. The moderate concentration of F was 90
      microg/d and the high concentration of F was 2700 microg/d. The moderate Ca
      concentration was 13 mg/d and the high Ca concentration was 260 mg/d. The
      moderate concentration of I was 3.5 microg/d and the low concentration of I was
      0.23 microg/d. After twenty weeks, body weight was measured. RESULTS: According
      to the results of factorial ANOVA, significant interaction effects of F with Ca
      were found (F = 5.933, P = 0.017). The empty body weight was measured at the end
      of the fifth month. When both iodine and fluorine were at the optimal level, the
      weight of group 2 [(262.5 +/- 47.1) g] and group 1 [(307.9 +/- 55.0) g] showed
      significant difference (t = 4.24, P < 0.05). When both iodine and fluorine were
      at low level, the weight of group 6 [(248.8 +/- 30.0) g] and group 5 [(293.3 +/-
      19.7) g] showed significant difference (t = 4.16, P < 0.05). Animals with optimal
      iodine and calcium [(269.3 +/- 27.3) g] showed significant difference compared to
      the weight of low level iodine and optimal fluorine [(307.9 +/- 55.0) g]. When
      the low level iodine and optimal calcium were applied, weight of group 7 [(261.9
      +/- 31.3) g] and group 5 [(293.3 +/- 19.7) g] showed significant difference. (t =
      2.94, P < 0.05). CONCLUSION: Interaction effects of F with Ca were found on body
      weight in rats.

PMID- 19175174
TI  - [Effects of p,p'-DDE and beta-BHC on the apoptosis of Sertoli cells in vitro].
AB  - OBJECTIVE: To explore the effects of p,p'-DDE and beta-BHC on the apoptosis of
      Sertoli cells in vitro via activation of Caspase. METHODS: Sertoli cells were
      treated in vitro for 24 hours with a serial concentrations of p,p'-DDE (10, 30
      and 50 micromol/L), beta-BHC (10, 30 and 50 micromol/L) and p,p'-DDE + beta-BHC
      (10, 30 and 50 micromol/L). The inhibitory group was first treated with 100
      micromol/L Caspase-3 inhibitor Ac-DEVD-CHO treating for 2 hours before 50
      micromol/L p, p'-DDE + 50 micromol/L beta-BHC 24 hours-treatment. The vitality of
      Sertoli cells was determined by MTT and the apoptosis rate was measured by AO/EB
      double fluorescence staining. The expressions of Caspase-3, Caspase-8 and Caspase
      9 were determined by RT-PCR. RESULTS: Average optical density (A) values were
      0.498 +/- 0.039, 0.481 +/- 0.065, 0.397 +/- 0.032 and 0.286 +/- 0.049 in p,p'-DDE
      groups (10, 30, 50 and 70 micromol/L), and 0.518 +/- 0.103, 0.490 +/- 0.060,
      0.454 +/- 0.054 and 0.302 +/- 0.030 in beta-BHC groups (10, 30, 50 and 70
      micromol/L). In the mixture-treated groups (10, 30 and 50 micromol/L), the
      average A values were 0.483 +/- 0.048, 0.473 +/- 0.058 and 0.337 +/- 0.052.
      Compared with the solvent control group (0.527 +/- 0.022) , 50 micromol/L group
      of p, p'-DDE, beta-BHC or their mixture caused a significant decrease of Sertoli
      cell viability (t values were 4.599, 2.716, 6.537 respectively, P < 0.05). AO/EB
      double fluorescence staining analysis showed that apoptosis rates of Sertoli
      cells were significantly increased with all treated groups. The expressions of
      Caspase-3, Caspase-8 and Caspase-9 were upregulated as the concentrations of p,p'
      DDE, beta-BHC and their mixture were increased. CONCLUSION: p,p'-DDE, beta-BHC
      and their mixture could induce the apoptosis of Sertoli cells in vitro which was
      associated with activation of Caspase-3 mediated by cleavage of Caspase-8 and
      Caspase-9.

PMID- 19175175
TI  - [Research on the procedure for recovery and species identification of Legionella
      from surface environmental water].
AB  - OBJECTIVE: To establish a set of procedure for recovery and species
      identification of Legionella from the surface environmental water. METHODS: Forty
      four water samples were collected in eight parks of Guangzhou city from August to
      November in 2006. The bacteriologic examination was performed by cultivation on
      BCYEalpha plate, and 108 presumptive Legionella colonies were picked and their
      homogeneous relationship was analyzed by using an amplified fragment length
      polymorphism (AFLP) method. Species identification was carried out by latex
      agglutination test, biochemical characterization, analysis of cellular fatty
      acids composition, 16 S rRNA gene and mip gene sequencing. RESULTS: Legionella
      was recovered among 27 (61.36%) samples of all eight parks, and 31 different
      strains were identified from those 108 presumptive Legionella isolates by AFLP
      method, including 20 strains of L. pneumophila, five strains of L. feeleii, four
      strains of L. longbeachae, one strain of L. oakridgensis and one strain of L.
      sainthelensi, and L. pneumophila could be easily differentiated by phenotypic and
      biochemical characteristics, latex agglutination test or analysis of the cellular
      fatty acids composition . However, uncertain factors were existing in those
      phenotypic identification methods as compared to the sequence analysis.
      CONCLUSION: The taxonomic analysis of the Legionellae family should be dependent
      on the 16 S rRNA gene or mip gene.

PMID- 19175176
TI  - [Changes of toll-like receptor, TNF-alpha and IL-10 in liver tissue of rats
      before and after intragastric infusion with alcohol with vibrio vulnificus
      sepsis].
AB  - OBJECTIVE: To detect the effects of antimicrobial agents on the toll-like
      receptor (TLR) and so on in liver tissue of rats after intragastric infusion with
      alcohol with vibrio vulnificus (VV) sepsis. METHODS: Sprague-Dawley rats were
      randomly divided into normal control group (N group, n = 6), rats after
      intragastric infusion with alcohol control group (group A, n = 6), drug
      intervention on rats after intragastric infusion with alcohol control group
      (group AA, n = 6), rats after intragastric infusion with alcohol with VV sepsis
      group (group AV, n = 24, killed at 2, 6, 12, 24 hours after injecting VV
      respectively, six rats per group), as well as drug intervention on rats after
      intragastric infusion with alcohol with vibrio vulnificus sepsis group (group
      AVA, n = 30, killed at 6, 12, 24 hours and one week after injecting VV
      respectively, six rats per group). The expressions and dynamic changes of TLR4
      mRNA and so on by RT-PCR in liver tissue of each group were measured. RESULTS:
      The expressions of TLR4 mRNA in AV-6 hours group was 0.775 +/- 0.101, the
      expressions of TLR4 mRNA in AVA-6 hours group was 0.600 +/- 0.064; the
      expressions of TLR4 mRNA in AV-12 hours group was 0.918 +/- 0.133, the
      expressions of TLR4 mRNA in AVA-12 hours group was 0.583 +/- 0.112; the
      expressions of TLR4 mRNA in AV-24 hours group was 0.732 +/- 0.110, the
      expressions of TLR4 mRNA in AVA-24 hours group was 0.512 +/- 0.118. Compared with
      AV group, the expressions of TLR4 mRNA in liver diminished greatly in AVA group
      at 6, 12 and 24 hours after being injected with VV (AVA-6 hours group compare
      with AV-6 hours group, t = -3.573, P < 0.01; AVA-12 hours group compared with AV
      12 hours group, t = - 4.722, P < 0.01; AVA-24 hours group compare with AV-24
      hours group, t = - 3.340, P < 0.01). CONCLUSION: The treatment with antibacterial
      agents may reduced the expression of TLR and so on in liver of rats after
      intragastric infusion with alcohol with VV sepsis. The treatment with
      antibacterial agents may regulate the balance of the inflammatory response in VV
      sepsis and generate the visible therapeutical effect for VV sepsis.

PMID- 19175177
TI  - [The effect of HPV16E7 DNA vaccine transdermal delivery with microneedle array].
AB  - OBJECTIVE: To study the effects of DNA vaccine transdermal delivery with
      microneedle array. METHODS: The pcDNA3.1-HPV16E7 recombinant vector acting as
      gene vaccine was established. The infiltration quantity of pcDNA3.1-HPV16E7
      getting across the microchannels generated by microneedle arrays in vitro was
      observed. 30 BALB/c mice were divided into 3 groups (experimental group, in vain
      plasmid group, negative control). Each group had 10 mice. Then immunized BALB/c
      mice with a dose of 200 microg with microneedle array every two weeks. The
      control groups did the same as that as the study groups. Two weeks after the
      third immunization, the serum and lymphocytes were separated to detect the
      functions of humoral immunity with indirect immunofluorescence test, while, the
      functions of cellular immunity with lymphocyte transformation test was also
      detected. RESULTS: The DNA vaccine could easily get across the microchannels
      generated by microneedle arrays in vitro. Moreover, the course was permanent and
      the whole infiltration quantity was comparatively high, reaching 0.73819 mg/cm2
      at the 30th hour. And among immunized BALB/c mouse, DNA vaccine transdermal
      delivery with microneedle array could induce specific antibodies. Lymphocyte
      transformation test showed that there was significant difference for the
      lymphocyte transformation rate between experiment (the average of lymphocyte
      transformation rate was 47.25%) and control group (the average of lymphocyte
      transformation rate was 30.00%) (chi2 = 12.903, P < 0.001). Also, the difference
      was found between in vain plasmid group (the average of lymphocyte transformation
      rate was 43.00%) and negative control(chi2 = 7.292, P = 0.007). While, no
      difference was observed in the experimental group and in vain plasmid group (chi2
      = 0.817, P = 0.366). CONCLUSION: The DNA vaccine combined administering with
      microneedle array might get across the microchannels generated by microneedle
      arrays in vitro and induce humoral and cellular immune response in vivo.

PMID- 19175178
TI  - [Comparison of the reliability of two ELISA kits for detecting IgM antibody
      against hepatitis E virus].
AB  - OBJECTIVE: To study the reliability of two ELISA kits for detecting IgM antibody
      against hepatitis E virus (HEV). METHODS: Serum samples from 92 healthy subjects,
      71 cases suspected of hepatitis E, 55 patients with confirmed diagnosis of acute
      hepatitis E, 50 individuals with rheumatoid factor (RF) positive and 54 persons
      with anti-HAV IgM positive were detected with three hepatitis E diagnostic kits.
      MP-IgM (MP, Singapore), Wantai-IgM and anti-HEV IgG (Wantai, China). HEV RNA was
      analyzed with RT-PCR in 52 of 71 cases suspected of hepatitis E. RESULTS: In
      healthy subjects,cases suspected of hepatitis E and confirmed acute hepatitis E,
      the concordance between the two anti-HEV IgM reagents was 73.39% (160/218) and
      the significant differences in the positive rates of two assays were not observed
      [46.79% (102/218) vs 44.04% (96/218), chi2 = 0.62, P > 0.05]. Of 71 patients
      suspected of hepatitis E, the sensitivity for diagnosing acute hepatitis E of
      Wantai-IgM and MP-IgM were 83.08% (54/65) and 78.46% (51/65) (chi2 = 0.16, P >
      0.05), respectively. Among those suspected of hepatitis E with HEV RNA positive,
      the sensitivity of Wantai-IgM was obviously higher than that of MP-IgM [(97.14%,
      34/35) vs (74.29%, 26/35), chi2 = 4.9, P < 0.05]. 48 of 55 patients (87.27%) with
      confirmed diagnosis of hepatitis E were Wantai-IgM positive while 37 (67.27%) was
      MP-IgM positive (chi2 = 4.0, P < 0.05). The specificity of Wantai-IgM was higher
      than MP-IgM [100.00% (202/202) vs 89. 11% (180/202), chi2 = 20.05, P < 0.005]. RF
      and anti-HAV IgM might cause MP-IgM false positive without interference on Wantai
      IgM. CONCLUSION: Wantai-IgM should be a good ELISA kit for the diagnosis of acute
      hepatitis E.

PMID- 19175179
TI  - [Molecular subtyping of Staphylococcus aureus isolated from a severe food
      poisoning].
AB  - OBJECTIVE: To study the molecular types of Staphylococcus aureus isolated from a
      severe food-poisoning and to trace the possible strains. METHODS: Real-time PCR
      was applied to detect nuc gene as a specific marker for S. aureus, mecA gene
      encoding methicillin resistance and 5 other genes encoding staphylococcal
      enterotoxins (sea, seb, see, sed, see). Isolates were also performed with 16S
      rRNA oligonucleotide sequence analyzing by DNAStar MegAlign 5.0 software and
      pulse-field gel electrophoresis (PFGE) by BioNumerics Version 4.0 software.
      RESULTS: The nuc gene was detected from the 10 isolated strains, sea and seb
      genes were detected from 7 strains. There were 4 16 S rRNA types and 5 PFGE types
      found from all the strains. CONCLUSIONS: Three relative S. aureus strains were
      involved in the severe food-poisoning at least. Molecular subtyping might give a
      molecular epidemiological evidence and support the source tracing of an outbreak.

PMID- 19175180
TI  - [Protein profiles of serum in gastric cancer at a high-risk area by SELDI-TOF
      mass spectrometry].
AB  - OBJECTIVE: To explore the specific and sensitive biomarkers for gastric cancer
      detection, a surface-enhanced laser desorption and ionization protein chip mass
      spectrometry (SELDI-TOF-MS) was used to generate protein profiles of serum in
      gastric cancer at a high-risk area. METHODS: A total of 36 gastric cancer cases
      and 46 subjects with superficial gastritis were selected from Linqu county,
      Shandong province, a high-risk area of gastric cancer. Serum samples were
      collected and Q10 protein chips were used to detect the serum proteomic patterns,
      and the sensitivity and specificity were assessed. RESULTS: For the comparison of
      the gastric cancer group (26 out of 36 gastric cancer cases) versus superficial
      gastritis group (37 out of 46 subjects), the 6 most discriminating peaks (m/z
      8587, 6945, 8243, 3899, 7035, and 9943) were identified by the ProteinChip Data
      Analysis System (ZUCIPDAS). The sensitivity and specificity of this pattern were
      88.5% and 97.3%, respectively. A total of 19 subjects (10 gastric cancer cases
      and 9 superficial gastritis subjects) was selected to test the accuracy of this
      pattern by using blind method, and the sensitivity and specificity were 80.0% and
      88.9% ,respectively. CONCLUSION: Our findings suggest that SELDI profiling of
      serum might be a potential for gastric cancer detection and screening in high
      risk population.

PMID- 19175181
TI  - Suppression of age-dependent increase in insulinemia in early middle-aged females
      with exercise habit.
AB  - Circulating insulin concentration has been suggested as a biomarker for human
      longevity. The goal of the study was to determine the insulin levels under a
      glucose-challenged condition for the sedentary and physical active females in
      early middle age. We measured serum insulin levels for following groups: young
      sedentary (Y-SED, age 19.7 +/- 0.2 years), middle-aged sedentary (M-SED, age 42.3
      +/- 3.1 years), young physically active (Y-EX, age 20.7 +/- 0.5 years), and
      middle-aged physically active (M-EX, age 40.3 +/- 2.8 years). Oral glucose
      tolerance test (OGTT) and insulin measurement were performed under overnight
      fasted condition. Triglyceride, cholesterol, body mass index (BMI), and waist-to
      hip ratio (WHR) were also determined in all subjects. While fasted glucose and
      insulin levels were not different among 4 groups, glucose and insulin levels
      under OGTT were greater in the M-SED group than those in the Y-SED group. The M
      EX subjects exhibited lower insulin levels on OGTT, as compared to the M-SED
      group, and were similar to the level of Y-SED. BMI and WHR of the M-SED group
      were comparable to those of the M-EX group. Triglyceride and cholesterol levels
      were highly associated with age and WHR but not the level of physical activity.
      The current study found a substantially greater insulin response on OGTT in the
      healthy sedentary females aged approximately 40, as compared to those in the
      young sedentary and the middle-aged physically active females, independent of
      weight status. The result of the study also suggests that accumulating 150 min of
      weekly exercise is sufficient to counteract the adverse effect of age on insulin
      sensitivity.

PMID- 19175182
TI  - Immunochemical localization of protein kinase Calpha in the biopsies of human
      hepatocellular carcinoma.
AB  - The purpose of this study was to elucidate the protein kinase C (PKC) alpha
      distribution in human hepatocellular carcinoma (HCC). The histoimmunopathologic
      technique was used to determine the localization and expression of PKCalpha in
      HCC biopsies. The HCC tissues were classified as cytosolic type (PKCalpha
      deposited in the cytoplasm in > 50% of cells) and membranous type for the
      remaining ones. There was a significant association of the membranous type with
      non-hepatitis C virus (HCV) infected patients. Moreover, the expression of
      PKCalpha in this type was significantly higher in HCC cells than that in the
      adjacent non-tumor liver cells. The result indicated that PKCalpha may play an
      important role in carcinogenesis of HCC patients with HBV infection and/or non
      HCV infection.

PMID- 19175183
TI  - Protective effects of deprenyl in transient cerebral ischemia in rats.
AB  - Cerebral ischemia leads to neuronal damage in the hippocampus and cognitive
      decline. Reactive oxygen species play an important role in the neuronal loss
      after cerebral ischemia and reperfusion injury. Deprenyl, an irreversible
      monoamine-oxidase B inhibitor, has antioxidant and neuroprotective effects
      against reactive oxygen species. In the present study, the effect of deprenyl on
      spatial memory impairment, oxidative stress and apoptotic neuronal cell death
      following transient cerebral ischemia in rats was investigated. Transient
      ischemia was induced by occlusion of left common carotid artery of rats for 30
      min and reperfusion for 24 h or 1 week. Rats received intraperitoneal injection
      of 1 mg/kg deprenyl (n = 24) or equal volume of saline (n = 24) for 14 days
      before the experiment. Deprenyl treatment attenuated spatial memory deficits
      following ischemia-reperfusion as measured by the Morris water maze task.
      Deprenyl treatment elicited a significant decrease in lipid peroxidation and
      increase in superoxide dismutase activities in ischemic rat brains. The number of
      TUNEL-positive cells decreased significantly in deprenyl-treated group when
      compared with the control group. The results show that deprenyl reduces the
      ischemia-induced oxidative stress and thus prevents spatial memory deficits and
      apoptotic neuronal cell death when it is administered before ischemia
      reperfusion.

PMID- 19175184
TI  - Regulation of LH receptor and PGF2alpha receptor signaling by the regulator of G
      protein signaling 2 (RGS2) in human and mouse granulosa cells.
AB  - Regulators of G protein signaling (RGS) proteins bind the G protein Galpha
      subunit in its active GTP-bound state and accelerate its GTPase activity, thus
      halting Galpha activity. Induction of RGS2 expression has been previously shown
      in the rat ovary in response to ovulatory stimulation; however, the significance
      of RGS2 in the ovary has not been established. This study reports the potential
      role of RGS2 in the signaling of two G protein-coupled receptors, the LH and
      PGF2alpha (FP) receptors, in the human and the mouse granulosa cell lines, KGN
      and NT-1. The RGS2 mRNA concentration was rapidly and transiently elevated by
      human chorionic gonadotropin (hCG) or PGF2alpha analogue cloprostenol and this
      was followed by a decline to basal level at 24 h. Expression of the downstream
      critical target gene of the LH and FP receptor signaling pathways, namely,
      cyclooxygenase 2 (COX2), was induced by hCG but was inhibited by cloprostenol.
      Overexpression of RGS2 attenuated hCG-induced COX2 transcription. However, this
      augmented cloprostenol-mediated suppression of COX2 transcription. Confocal
      microscopy and immunoblot analysis were adopted to monitor the intracellular
      localization of RGS2 in COS-7 cells carrying the FP receptor and expressing RGS2
      GFP or FLAG-RGS2. RGS2 was initially located predominantly in the nucleus and
      activation of the FP receptor resulted in RGS2 translocation from nucleus to the
      cell membrane. Thus, RGS2 expression was upregulated by LH receptor and FP
      receptor activation and modulation of partner receptor signaling by RGS2 may
      require RGS2 translocation from the nucleus to the plasma membrane.

PMID- 19175185
TI  - Anti-inflammatory effects of LK-3, on LPS-induced sepsis in rats.
AB  - Dextromethorphan (DM), an antitussive agent, has been shown to have anti
      inflammatory and immunomodulatory effects in vitro. Thus, the aim of this study
      was to evaluate the effects of LK-3, an analog of DM, on sepsis induced by
      intravenous (i.v.) administration of lipopolysaccharide (LPS; 10 mg/ kg) in
      anesthetized Wistar rats. Results demonstrated that post-treatment with LK-3 (4
      mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes (e.g.,
      hypotension and bradycardia) in rats treated with LPS. Meanwhile, LK-3 (4 mg/kg)
      significantly inhibited the elevation of plasma tumor necrosis factor-alpha, as
      well as values of glutamate-oxalacetate transaminase (GOT) and glutamate-pyruvate
      transaminase (GPT) caused by LPS. The induction of inducible NO synthase and the
      overproduction of NO and superoxide anions by LPS were also reduced by post
      treatment of LK-3. Moreover, infiltration of neutrophils into the lungs and liver
      of rats 8 h after treatment with LPS was also reduced by post-treatment with LK
      3. In conclusion, the beneficial effects of LK-3 on LPS-induced sepsis resulted
      from its anti-inflammatory and antioxidant effects.

PMID- 19175186
TI  - Hyporeactivity of renal artery to angiotensin II in septic rats.
AB  - Although reduced vascular reactivity to vasoconstrictors has been well
      documented, it is not clear whether renal blood flow (RBF) and renal vascular
      response exhibit the same pattern following sepsis. We examined RBF and renal
      vascular response during early sepsis. Male Sprague-Dawley rats underwent cecal
      ligation and puncture (CLP)-induced sepsis. At 5 h after CLP or sham operation,
      RBF and plasma nitric oxide (NO) concentration were measured. Moreover,
      angiotensin II (50 ng/kg body weight) was employed to evaluate the renal vascular
      response (n = 12 rats/group). The results showed that CLP caused higher heart
      rate (HR), RBF and lower renal vascular resistance (RVR). In addition, plasma
      nitrite-nitrate (NOx) increased significantly after CLP. After angiotensin II
      infusion, maximal response in mean blood pressure (MBP), RBF and RVR were less in
      CLP rats. Thus, we found that CLP induced hyporeactivity of renal artery together
      with overproduction of NO during an early stage of sepsis.

PMID- 19175187
TI  - Short-term versus long-term intermittent hypobaric hypoxia on cardiac fibrosis
      and Fas death receptor dependent apoptotic pathway in rat hearts.
AB  - It is unknown if short-term and long-term intermittent hypobaric hypoxic
      challenges both exert pro-apoptotic effects on Fas death receptor-dependent
      apoptotic pathway in rat hearts. Seventy-two Sprague-Dawley rats were randomly
      assigned into two groups. First, short-term intermittent hypobaric hypoxia
      (STIHH)-normobaric normoxia (n = 12), hypobaric hypoxia (380 mmHg, 12% O2, 8
      hrs/day) for 1 day (n = 12), and for 4 days (n = 12) and second, long-term
      intermittent hypobaric hypoxia (LTIHH)-normobaric normoxia (n = 12), hypobaric
      hypoxia for 1 week (n = 12) and 2 weeks (n = 12). After STIHH or LTIHH challenge,
      Fas receptor related pathway and histopathological analysis in the excised left
      ventricle was determined by Western blotting, RT-PCR, Hematoxylin-eosin staining,
      Masson trichrome staining and TUNEL assay. Fas death receptor and TNFalpha were
      significantly decreased after STIHH whereas Fas receptor, TNFalpha, FAS
      associated death domain (FADD), and caspase 8 were increased after LTIHH. In
      addition, cardiomyocyte disarray and fibrosis were observed in 1 week LTIHH.
      Cardiac hypertrophy and more severe disarray, fibrosis and cardiac apoptotic
      activities were observed in 2 week LTIHH. STIHH exerts anti-apoptotic effects on
      hearts such as downregulation of TNFalpha and Fas receptor whereas LTIHH exerts
      pro-apoptotic effects such as upregulation of TNFalpha and Fas-mediated apoptotic
      pathways and lead to cardiac fibrosis and apoptosis. Our findings imply that
      short-term versus long-term intermittent hypobaric hypoxia exerted protective
      versus deleterious effects on hearts.

PMID- 19175188
TI  - Physiological, psychological and autonomic responses to pre-operative
      instructions for patients undergoing cardiac surgery.
AB  - Several studies have reported that the experience may induce emotional reactions
      before and after surgery. Various Studies have demonstrated that effective pre
      operative information reduces stress and anxiety levels. However, little is known
      about the effect of pre-operative instruction on autonomic responses as measured
      by heart rate variability (HRV) before cardiac surgery. Ninety-one patients were
      randomly assigned to video-tape viewing and teaching booklet group.
      Electrocardiogram was monitored before and after pre-operative instruction. HRV
      was analyzed with spectral analysis of frequency domains of heart rate and
      categorized into low and high frequency (LF and HF). After pre-operative
      instruction, subjects completed a score of perceived stress and helpfulness. In
      this study, we found that pre-operative instruction with video-tape was similarly
      effective as teaching booklets on patients' perceived stress, perceived
      helpfulness and recovery outcomes. The decrease in HF% and increase in LF/HF
      ratio of HRV indicate a change in sympathovagal balance toward a lower
      parasympathetic activity after pre-operative instruction in subjects of both
      groups. However, the perceived helpfulness of pre-operative instruction may often
      be associated with a relatively less sympathetic activity. Further studies are
      needed to determine the optimal timing to enhance the positive effects on the
      sympathovagal balance after pre-operative instruction.

PMID- 19175189
TI  - The time window of intermittent hypoxia intervention after middle cerebral artery
      occlusion.
AB  - It was known that preconditioning hypoxia can reduce the damage caused by
      ischemia. However, there was no study investigating the effects of intermittent
      hypoxia post ischemia. The purpose of this study was to investigate the time
      window for administering the hypoxia for beneficial effects after cerebral
      ischemic damage. According to the recovery days post transient middle cerebral
      occlusion (MCAO), the rats were randomly assigned to one of the 4 groups (n = 20
      for each group, I, II, III, and IV). Rats were then assigned to one of the 2
      subgroups (a and b). Rats in group Ia, IIa, IIIa, and IVa were exposed to 7 days
      of intermittent hypoxia (12% O2 for 4 hours per day) after recovery 1, 2, 3, and
      7 days from MCAO, respectively. Rats in group Ib, IIb, IIIb, and IVb rested for 7
      days in the same hypoxia chamber without hypoxia exposure after 1, 2, 3, and 7
      days post MCAO, respectively. The mortality rate of rats received hypoxia after 1
      day' and 2 days' recovery post MCAO was 40% (P = 0.087) and 10% (P = 0.5),
      respectively. The mean infarct volume of rats received hypoxia after 7 days'
      recovery was significantly less than that of the comparable control group (9.23
      +/- 0.71% vs. 13.32 +/- 1.26%; P = 0.013), and no rats died in this group. In
      summary, intermittent hypoxia intervention for 7 days after 7 days of recovery
      post ischemia can reduce the infract volume, and does not increase the mortality
      rate. According to our results, we suggest that 7 days post ischemia may be the
      suitable time to begin the intermittent hypoxia intervention to enhance the
      recovery from cerebral ischemia.

PMID- 19175190
TI  - The use of alternative anti-coagulation strategies for a nocturnal home
      hemodialysis patient with heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a potentially catastrophic
      hyercoagulable state. The prevalence of HIT in individuals doing nocturnal home
      hemodialysis (NHD) is unknown and the appropriate treatment protocol has yet to
      be determined. The objective is to describe the clinical course and treatment
      plan ofa patient who developed HIT while undergoing NHD. A 49-year-old man with a
      past history of end stage renal disease (ESRD) of unknown etiology was initiated
      on NHD in February 2005. His clinical and biochemical parameters improved after
      conversion to NHD. However, excessive bleeding at the vascular access sites
      complicated his treatments. Clinical investigations revealed development of HIT
      Alternative therapeutic strategies were attempted to enable our patient to
      continue NHD: unfractionated heparin, citrated regional anticoagulation,
      Danaparoid, and Argatroban. In conclusion, NHD patients with HIT pose a specific
      clinical challenge. We speculate that the augmented exposure of heparin coupled
      with a primed autoimmune response may be responsible for the development of HIT
      in our patient. Further research is required to elucidate the appropriate
      clinical monitoring and treatment strategy for this patient.

PMID- 19175191
TI  - Weekly energy expenditure and quality of life in hemodialysis patients.
AB  - This study examined the relationship between physical activity patterns and
      quality of life among hemodialysis patients. While undergoing hemodialysis, 19
      patients (31-82 years; 60.2 +/- 17.4 yrs, mean +/- SD) completed a physical
      activity and the Short-Form 36 (SF-36) questionnaire. Individuals were separated
      into either a high- or low-energy expenditure group. The high-energy expenditure
      group had significantly higher total SF-36 scores (58.35 +/- 4.49 vs. 42.85 +/-
      3.86, mean +/- SE, p = 0.028) and physical functioning scores (62.22 +/- 8.00 vs.
      27.14 +/- 3.16, mean +/- SE, p = 0.002) compared to individuals in the low-energy
      expenditure group. Members in the high-energy group tended to score higher on
      social functioning, general health, and role limitations. Increasing weekly
      energy expenditure, either through physical activity or household tasks, may
      increase quality of life and overall level of physical functioning in patients
      with end stage renal disease.

PMID- 19175192
TI  - Medication reconciliation in hemodialysis patients.
AB  - Medication reconciliation is an effective process to reduce adverse drug events
      (ADEs) and harm associated with the loss of medication information as patients
      transfer between health care settings. Patients with end stage renal disease
      (ESRD) are at a high risk of experiencing drug-related problems (DRPs) because
      they take many medications, have multiple comorbidities, and require frequent
      medication changes. We evaluated the potential impact of medication
      reconciliation and optimization in the ambulatory care setting at the time of
      patient transfer from an in-centre dialysis unit to a satellite dialysis unit.
      Overall, 15 patients (78.8%) had at least one unintended medication variance. The
      majority of unintended variances (56%) were caused by the physician/nurse
      practitioner (NP) omitting an order for medication that the patient was taking.
      In this small study, medication reconciliation was effective at identifying and
      rectifying medication errors and optimizing pharmacotherapy at the time of
      transfer from an in-centre hemodialysis to a satellite dialysis unit.

PMID- 19175193
TI  - The Northern Alberta Renal Program dialysis bus.

PMID- 19175194
TI  - The use of ACE inhibitors and ARBs in severe chronic kidney disease: point
      counterpoint.

PMID- 19175195
TI  - Common causes of open-circuit recreational diving fatalities.
AB  - Diving fatalities causes were investigated in 947 recreational open-circuit scuba
      diving deaths from 1992-2003. Where possible, cases were classified at each step
      of a four step sequence: trigger, disabling agent, disabling injury, cause of
      death (COD). The most frequent adverse events within each step were: (a) triggers
      41% insufficient gas, 20% entrapment, 15% equipment problems; (b) disabling
      agents--55% emergency ascent, 27% insufficient gas, 13% buoyancy trouble; (c)
      disabling injuries--33% asphyxia, 29% arterial gas embolism (AGE), 26% cardiac
      incidents; and (d) COD--70% drowning, 14% AGE, 13% cardiac incidents. We
      concluded that disabling injuries were more relevant than COD as drowning was
      often secondary to a disabling injury. Frequencies and/ or associations with risk
      factors were investigated for each disabling injury by logistic regression. (The
      reference group for each injury was all other injuries.) Frequencies and/or
      associations included: (a) asphyxia--40% entrapment (Odds Ratio, OR > or = 30),
      32% insufficient gas (OR = 15.9), 17% buoyancy trouble, 15% equipment trouble (OR
      = 4.5), 11% rough water, drysuit (OR = 4.1), female gender (OR = 2.1); (b) AGE-
      96% emergency ascent (OR > or = 30), 63% insufficient gas, 17% equipment trouble,
      9% entrapment; (c) cardiac incidents--cardiovascular disease (OR = 10.5), age >
      40 (OR = 5.9). Minimizing the frequent adverse events would have the greatest
      impact on reducing diving deaths.

PMID- 19175196
TI  - Doppler ultrasound surveillance in deep tunneling compressed-air work with Trimix
      breathing: bounce dive technique compared to saturation-excursion technique.
AB  - The Western Scheldt Tunneling Project in The Netherlands provided a unique
      opportunity to evaluate two deep-diving techniques with Doppler ultrasound
      surveillance. Divers used the bounce diving techniques for repair and maintenance
      of the TBM. The tunnel boring machine jammed at its deepest depth. As a result
      the work time was not sufficient. The saturation diving technique was developed
      and permitted longer work time at great depth. Thirty-one divers were involved in
      this project. Twenty-three divers were examined using Doppler ultrasound. Data
      analysis addressed 52 exposures to Trimix at 4.6-4.8 bar gauge using the bounce
      technique and 354 exposures to Trimix at 4.0-6.9 bar gauge on saturation
      excursions. No decompression incidents occurred with either technique during the
      described phase of the project. Doppler ultrasound revealed that the bubble loads
      assessed in both techniques were generally low. We find out, that despite longer
      working hours, shorter decompression times and larger physical workloads, the
      saturation-excursion technique was associated with significant lower bubble
      grades than in the bounce technique using Doppler Ultrasound. We conclude that
      the saturation-excursion technique with Trimix is a good option for deep and long
      exposures in caisson work. The Doppler technique proved valuable, and it should
      be incorporated in future compressed-air work.

PMID- 19175197
TI  - Pulmonary effects of submerged exercise while breathing 140 kPa oxygen.
AB  - Pulmonary effects of prolonged mild intermittent underwater cycle ergometer
      exercise were assessed after single and repeated four-hour dives to 12 feet. With
      air, five daily dives (surface interval [SI], 20 hours), and with 100% oxygen,
      single dives, five daily dives, and afternoon-morning dives (SI, 15 hours) were
      conducted. Air divers had no symptoms or abnormal pulmonary function values but
      showed slight decreases within the normal range in forced expired volume in one
      second (FEV1; -0.45%/day) and forced expired flow between 25% and 75% of volume
      expired (FEF25-75; -0.8%/day). After one oxygen dive, incidences of mild symptoms
      or reduced pulmonary function were not different with exercise from those
      resting, but during five dives, decreases were significant in FEF25-75 (
      1.8%/day) and diffusing capacity of the lung for carbon monoxide (D(L)CO; 
      1.2%/day), estimated to cause abnormal values in 25% of divers in nine to ten
      days. Following afternoon-morning dive pairs, changes in FEV1 and FEF25-75 were
      similar to those after nine or four daily dives, respectively. Exercise increases
      the injurious pulmonary effects of 140 kPa oxygen, and oxygen, those of exercise.
      A one-day break should follow two 4-hour exercise oxygen dives with surface
      intervals of 15 to 20 hours.

PMID- 19175198
TI  - Antibiotic and hyperbaric oxygen therapy in the management of post-operative
      discitis.
AB  - OBJECTIVE: Despite the use of antibiotics, the management of postoperative
      discitis (POD) still presents a challenge. This study was designed to evaluate
      the effect of adjuvant hyperbaric oxygen (HBO2) therapy on the duration of
      antibiotic treatment. METHODS: Between 1999 and 2004, 22 patients diagnosed with
      POD were treated with antibiotic and HBO2 therapy. There were 14 male (63.6%) and
      8 female (36.3%) patients, and their mean age at the time of surgery was 45.4
      years (range, 20-59 years). Diagnosis of a POD was established on the basis of
      clinical, laboratory, and radiographic findings. All patients were given a 4-week
      course of vancomycin (1g i.v. every 12 h). Additionally, patients received HBO2
      (100% O2 at 2.4 ATA for 90 min) twice daily for the initial five consecutive
      days, and an additional treatment (100% O2 at 2.4 ATA for 90 min daily) was given
      for 25 days. The duration of follow-up was 24 months. RESULTS: This treatment
      modality allowed infection control and healing for all 22 patients with 0%
      recurrence rate. HBO2 treatment was tolerated well. CONCLUSION: This series
      represents the first reported group of POD patients treated with antibiotic and
      HBO2 therapy. Our preliminary results indicate that the length of time on
      antibiotic therapy can be shortened with the use of HBO2 as an adjunctive
      treatment. Erythrocyte sedimentation rates and serum C-reactive protein levels
      returned to the preoperative levels earlier (within 8-30 days after the
      initiation of treatment) and a reasonable length of immobility was obtained (mean
      12.2 days). After completion of the one-month period of antibiotic and HBO2
      therapy, patients were accepted disease-free regarding pain and mobility.

PMID- 19175199
TI  - Case report: successful use of hyperbaric oxygen therapy for a complete scalp
      degloving injury.
AB  - We report a case of a complete scalp degloving injury in a 43-year-old previously
      healthy, tobacco-using female whose hair was caught in a tractor power take-off
      causing an instantaneous total scalping injury. Microsurgical replantation was
      started 4 hours after injury with the surgical procedure lasting 4 hours. Only
      the superficial temporal arteries were reanastomosed with no venous anastomosis
      possible. Hyperbaric oxygen (HBO2) treatment at 2.5 atmospheres absolute (ATA)
      for 90 minutes was administered immediately after surgery due to duskiness of the
      flap. Further HBO2 treatments were administered twice daily for seven days and
      then once daily for 30 days. Additionally, leech therapy was used for the first
      ten postoperative days. The patient's right auricle and most of the left auricle
      were completely lost. Despite the tenuous vascular inflow and initially absent
      venous drainage, at 3 month follow-up there was reepithelialization of her scalp
      except for an area of granulation tissue in the occipitoparietal area. At one
      year follow-up the area of granulation tissue was reduced, but there was no
      detectable hair growth or nerve function. We propose that HBO2 may facilitate
      tissue survival in scalp degloving injuries in the face of incomplete surgical
      revascularization.

PMID- 19175200
TI  - Hyperbaric oxygen therapy in autism: is there evidence?

PMID- 19175201
TI  - Neurological decompression illness (DCI) responds favorably to hyperbaric oxygen
      treatment (HBOT) even when treatment is substantially delayed.

PMID- 19175202
TI  - Early development of the myxozoan Buddenbrockia plumatellae in the bryozoans
      Hyalinella punctata and Plumatella fungosa, with comments on taxonomy and
      systematics of the Myxozoa.
AB  - We undertook a detailed ultrastructural investigation to gain insight into the
      early stages of development of the vermiform myxozoan, Buddenbrockia plumnatellae
      Schroder, 1910 in two bryozoan hosts. Early cell complexes arise in the
      peritoneum after division and migration of isolated cells in the host body wall.
      The development of cell junctions linking the outer (mural) cells of the complex
      then produces a sac enclosing a mass of inner cells. Elongation to the vermiform
      stage (myxoworm) occurs during multiplication and reorganisation of the inner
      cells as a central core within the single-layered sac wall. The core cells
      develop into muscle and sporogonic cells separated from the mural cells by a
      basal lamina. Myogenesis occurs along the length of the myxoworm from cells that
      differentiate from the central core, and is independent of elongation. Four
      primary sporogonic cells maintain positions close to the basal lamina, between
      muscle cells, while giving rise to secondary sporogonic cells that eventually
      become free in the central cavity. At least some secondary sporogonic cells
      undergo meiosis. In view of the recent confirmation of the phylogenetic affinity
      of Buddenbrockia with the Cnidaria, we postulate how features observed in
      Buddenbrockia may be homologous with cnidarian structures. Finally we propose a
      new family name, Buddenbrockiidae, to replace Saccosporidae which was proposed
      previously in breach of the International Code of Zoological Nomenclature.

PMID- 19175203
TI  - Phylogeny of Flabellulidae (Amoebozoa: Leptomyxida) inferred from SSU rDNA
      sequences of the type strain of Flabellula citata Schaeffer, 1926 and newly
      isolated strains of marine amoebae.
AB  - New strains of non-vannellid flattened amoebae isolated from fish, an
      invertebrate and the marine environment were studied together with Flabellula
      citata Schaeffer, 1926 selected by morphology as a reference strain. The study
      revealed a paucity of features distinguishing individual strains at the generic
      level, but clearly evidenced mutual phylogenetic relationships within the
      assemblage of strains as well as their affiliation to the Leptomyxida. In this
      study, the SSU rDNA dataset of leptomyxids was expanded and a new branching
      pattern was presented within this lineage of Amoebozoa. Sequences of three newly
      introduced strains clustered in close relationship with the type strain of F.
      citata, the type species of the genus. Three strains, including one resembling
      Flamella sp., were positioned within a sister-group containing Paraflabellula
      spp. Results of phylogenetic analysis confirmed doubts of previous authors
      regarding generic assignment of several Rhizanmoeba and Ripidomnyxa strains.

PMID- 19175204
TI  - Gyrodactylus pisculentus sp. n. (Monogenoidea: Gyrodactylidae) associated with
      mortality of the northern pipefish, Syngnathus fuscus (Syngnathiformes:
      Syngnathidae) at the Woods Hole Science Aquarium.
AB  - Gyrodactylus pisculentus sp. n. is described from the head, body and fins of the
      northern pipefish, Syngnathus fuscus Storer (Syngnathidae) from the environs of
      Woods Hole, Massachusetts, USA. The new species is compared with Gyrodactylus
      shorti and Gyrodactylus syngnathi, species previously recorded from pipefish in
      the United States and Norway, respectively. Gyrodactylus pisculentus was
      frequently associated with mortality of northern pipefish held in quarantine at
      the Woods Hole Science Aquarium during 2002-2005. The clinical account of the
      infections and treatment protocols are presented.

PMID- 19175205
TI  - Microhabitat selection of Discocotyle sagittata (Monogenea: Polyopisthocotylea)
      in farmed rainbow trout.
AB  - Microhabitat preference of the monogenean Discocotyle sagittata (Leuckart, 1842)
      was determined in late spring and late autumn in rainbow trout, Oncorhynchus
      mykiss (Walbaum), reared in the Isle of Man, U.K. Discocotyle sagittata exhibits
      a preference for attachment to anterior gill arches: 29% of all worms occurred on
      gill arch I, 28% on II, 25% on III and 18% on IV. This distribution pattern on
      the introduced salmonid species is the same as reported for its native European
      host, the brown trout Salmo trutta (L.). Previous experimental work suggested
      that invasion is a passive process followed by post-invasion migration to
      anterior gill arches; the present work provides evidence of equivalent site
      selection taking place in fishes maintained under conditions promoting continuous
      reinfection in aquaculture. Migration may be density-dependent, since a
      significant inverse association was found between the intensity of mature
      parasites and their proportion on anteriormost gill arch I.

PMID- 19175206
TI  - Philometra sawara sp. n. and a redescription of Philometra sciaenae Yamaguti,
      1941 and Philometra nemipteri Luo, 2001 (Nematoda: Philometridae): a
      morphological and molecular approach.
AB  - Morphological data and molecular analyses are used to describe the taxonomy of
      philometrid nematodes of the genus Philometra Costa, 1845, found in the gonads of
      marine fishes in Japan. A new Philomnetra species, P. sawara sp. n., is described
      based on male and female specimens collected from the gonads of Scomberomorus
      niphonius (Cuvier) (Japanese Spanish mackerel). Two additional species,
      Philometra nemipteri Luo, 2001 and Philometra sciaenae Yamaguti, 1941, are
      confirmed as valid species and are redescribed based on specimens collected from
      the gonads of Nemipterus virgatus (Houttuyn) (golden threadfin bream) and
      Pennahia argentata (Houttuyn) (silver croaker), respectively. Male P. nemipteri
      are first reported and described in this study. Redescriptions of female P.
      nemipteri and male and female P. sciaenae were also necessary based on our
      morphological observations. A molecular comparison of the internal transcribed
      spacer 2 (ITS2) region of the ribosomal DNA between P. sawara, P. nemipteri, P.
      sciaenae, and previously reported philometrid nematodes from the genus Philometra
      and Philometroides Yamaguti, 1935 supports the conclusion that the three
      Philometra species in the current study are independent. An ITS2-derived
      neighbour-joining tree, consisting of both the current specimens and previously
      described Philometra and Philometroides species, is also presented.

PMID- 19175207
TI  - Quill mites of the genus Syringophilopsis Kethley, 1970 (Acari: Syringophilidae)
      from North American birds.
AB  - Seven mite species belonging to the genus Syringophilopsis Kethley, 1970 (Acari:
      Prostigmata: Cheyletoidea) are recorded from 10 passeriform host species from the
      USA. Three new species are described and illustrated: Syringophilopsis
      polioptilus sp. n. from Polioptila caerulea (Linnaeus) (Polioptilidae); S.
      empidonax sp. n. from Empidonax hamrnmondii (Vesey) and Empidonax wrightii Baird
      (Tyrannidae); and S. sialiae sp. n. from Sialia mexicana Swainson (Turdidae). In
      addition, records of new hosts are given: Turdus migratorius Linnaeus (Turdidae)
      for Syringophilopsis turdus (Fritsch, 1958); three tyrannid species (Tyrannidae),
      Myiarchus crinitus (Linnaeus), M. cinerascens (Lawrence) and Tyrannus verticalis
      Say for S. tyranni Bochkov et Galloway, 2004; Euphagus cyanocephalus (Wagler)
      (Icteridae) for S. elongatus (Ewing, 1911); and two parulid species (Parulidae),
      Dendroica graciae Baird and Wilsonia pusilla (Wilson) for S. dendroicae Bochkov
      et Galloway, 2001. All known species of the genus Syringophilopsis from the
      Nearctic Region are summarized in tabular form. Syringophilopsis porzanae Bochkov
      et Galloway, 2004 is reassigned to the genus Ascetonmylla Kethley, 1970.

PMID- 19175208
TI  - A redescription of Trichosurolaelaps dixous Domrow, 1972 (Acari: Laelapidae),
      from Trichosurus cunninghami (Marsupialia: Phalangeridae) from southern
      Australia.
AB  - The adults of Trichosurolaelaps dixous Domrow, 1972 are redescribed from a
      population of Trichosurus cunninghami Lindenmayer, Dubach et Viggers, 2002 in
      south-eastern Australia. The nymphal stages are described for the first time.
      Morphologically, T. dixous is similar to Trichosurolaelaps crassipes Womersley,
      1956. Morphological differences between the prefemale deutonymphs and adult
      females of the two mite species are the presence of a single large ventral spur
      on tibia I of T. dixous. Males of T. dixous could not be distinguished from T.
      crassipes morphologically and the idiosomal length of male T. dixous was variable
      (475-683 microm). Protonymphs of the two mite species differed only in size, with
      that of T. dixous being larger. Although T. crassipes was prevalent in a
      sympatric population of Trichosurus vulpecula and has been reported from other
      populations of T. cunninghami in southern Australia, it was never recovered from
      the population of T. cunninghami studied.

PMID- 19175209
TI  - Ultrastructure of microtriches on the scolex of Cyathocephalus truncatus
      (Cestoda: Spathebothriidea).
AB  - The scolex surface of the mature spathebothriidean Cyathocephalus truncatus
      (Pallas, 1781), a parasite of the brown trout Salmo trutta fario L., was studied
      using scanning and transmission electron microscopy. A particular attention was
      paid to microtriches, unique structure on the surface of the Cestoda. The scolex
      of C. truncatus is covered with two types of filiform microtriches (filitriches):
      aciculate (approximately 3 microm long) and capillate (approximately 10 microm
      long). Capillate microtriches, which have never been reported in any other
      spathebothriideans, are described for the first time using transmission electron
      microscopy. The tegument covered with filiform microtriches only (no spiniform
      microtriches are present) is typical of cestode groups supposed to be the most
      basal, e.g., Gyrocotylidea, Spathebothriidea, and Caryophyllidea.

PMID- 19175210
TI  - Development of the philometrids Philometra overstreeti and philometroides
      paralichthydis in the experimentally infected copepod Oithona colcarva.
AB  - Philometra overstreeti Moravec et de Buron, 2006 and Philomnetroides
      paralichthydis Moravec et de Buron, 2006 are common parasites of the southern
      flounder, Paralichthys lethostigma Jordan et Gilbert. Because the life cycles of
      these parasites are unknown, our goal was to assess whether species of copepod
      commonly found in our estuaries could serve as intermediate hosts for these
      philometrids. Individuals of five species of copepods were collected and exposed
      to L1 larvae of each philometrid species. The cyclopoid Oithlona colcarva Bowman
      was the only species to become successfully infected. Successive moulting of
      philometrid larvae in the haemocoel of the copepods was studied using
      transmission electron microscopy. At 23 degrees C the moult from L1 to L2 was
      observed for both species as early as 24 h post exposure to L1 larvae. The moult
      from L2 to L3 was initiated within 2 days post exposure and completed by 6-7 days
      post exposure. Some parasite-induced tissue damage occurred in the copepod but no
      cellular response against larval philometrids was observed.

PMID- 19175211
TI  - Redescription and systematic status of Neocapillaria phoxini Yu et Wang, 1994
      (Nematoda: Capillariidae).
AB  - Re-examination of the syntypes of the capillariid nematode Neocapillaria phoxini
      Yu et Wang, 1994, the type species of Neocapillaria Yu et Wang, 1994, described
      from the intestine of the freshwater fish Phoxinus lagowskii variegatus Gunther
      (Cyprinidae) from China, confirmed its morphological similarity with species of
      Freitascapillaria Moravec, 1987, to which it is transferred as Freitascapillaria
      phoxini (Yu et Wang, 1994) comb. n. Consequently, Neocapillaria Yu et Wang, 1994
      (a homonym to Neocapillaria Moravec, 1987) and Sinocapillaria Moravec et Spratt,
      1998 become junior synonyms of Freitascapillaria. Skrjabinocapillaria gigantea is
      transferred to Freitascapillaria as F. gigantea (Wang, 1984) comb. n.

PMID- 19175212
TI  - Retail care off fast track. Trend could hurt access for uninsured: study.

PMID- 19175213
TI  - Looking back on 2008.

PMID- 19175214
TI  - They do things a little differently. Providers branching out internationally face
      a host of legal, regulatory issues.

PMID- 19175215
TI  - Minds on the edge.

PMID- 19175217
TI  - Yes, we can all be insured.

PMID- 19175216
TI  - Express-lane medicine.

PMID- 19175218
TI  - A stem-cell surprise.

PMID- 19175219
TI  - Make that a double.

PMID- 19175220
TI  - Care from afar.

PMID- 19175221
TI  - Can God love Darwin, too?

PMID- 19175222
TI  - You and your quirky kid.

PMID- 19175223
TI  - Starting the good life in the womb.

PMID- 19175224
TI  - Waiter, please hold the wheat.

PMID- 19175225
TI  - Homeroom zombies.

PMID- 19175226
TI  - The cultural war on diabetes.

PMID- 19175227
TI  - Raising healthy kids.

PMID- 19175228
TI  - National trends and determinants of hospitalization costs and lengths-of-stay for
      uterine fibroids procedures.
AB  - Uterine fibroid admissions in the nation's hospitals have grown more than 20
      percent over the past five years. Substantial variations exist in inpatient
      treatment patterns. In spite of this dramatic growth, there are no national
      studies of the hospital costs associated with the treatment of uterine fibroids
      in the hospital setting. Using 11 years of data (1993-2003) from the Healthcare
      Cost and Utilization Project, a nationally representative 20 percent sample of
      the nation's inpatient admissions, trends in hospital charges, costs, and lengths
      of stay (LOSs) are reported. For 2001 to 2003, determinants of hospital costs and
      LOS for inpatients with a primary diagnosis of uterine fibroids were analyzed
      using univariate analyses and regression techniques. Hysterectomies for women
      with a primary diagnosis of uterine fibroids have in-hospital costs of over $1.5
      billion. Among the major procedures for treating uterine fibroids, in 2003, total
      abdominal hysterectomy had the longest LOS, averaging 2.9 days with a mean cost
      of $6331. In contrast, the treatment with the shortest LOS, 1.72 days, was
      laparoscopically assisted vaginal hysterectomy but it had the highest mean costs
      of $7108. In 2003, supracervical hysterectomies and myomectomies had mean costs
      of $6809 and $6707, respectively. Multivariate results show that patient
      characteristics and structural aspects of the hospital are strong predictors of
      lengths of stay and cost per day but there are major differences across some of
      the surgical procedures. Although the patient characteristics-insulin-dependent,
      non-insulin dependent diabetes, obesity, morbid obesity, smoker, hypertension,
      congestive heart failure, chronic obstructive pulmonary disease-all have
      significant impacts on LOS and cost per day for some of the major uterine fibroid
      treatments, they are not consistent. Compared with white women, black, Hispanic,
      and Asian/Pacific Island women all had higher lengths of stay and costs per day.
      Bedsize and teaching status are generally positively associated with lengths of
      stay and costs per day; for-profit status always had a significant positive
      association with LOS and cost per day. Hospital costs for treating women with
      uterine fibroids are continuing to grow. Further research on the determinants of
      the resource utilization could be helpful in predicting and alleviating these
      costs and improving patient care.

PMID- 19175229
TI  - Recent developments in false claims enforcement: a minefield for health care
      providers.
AB  - Actions under the False Claims Act represent potentially billions of dollars in
      damages returned to the state and federal governments each year for fraud
      recovery. Over the past several years, health care providers have been the target
      of about half of the FCA suits filed and have paid out an even greater percentage
      of the damages recovered. Because of the enumerable opportunities for fraud,
      waste, and abuse in the health care industry, it will likely continue to be a
      prominent target of FCA suits. Key provisions of the Deficit Reduction Act of
      2005, effective on January 1, 2007, will only increase the reach of the FCA.
      Providers beware.

PMID- 19175230
TI  - A primer on EVA for health care providers.
AB  - Unlike accounting earnings, economic profit (EVA) is a measure of a company's
      true earnings because it fully "accounts" for the costs of all forms of
      financing, including debt and equity. In the EVA view, a company is not truly
      profitable unless it earns a return on capital that bests the opportunity cost of
      capital. That being said, the question addressed here is how to measure the
      economic profit of providers in the health care sector, which is largely
      comprised of not-for-profit organizations such as clinics, laboratories, and
      hospitals.

PMID- 19175231
TI  - Hospital nurse productivity enhancement.
AB  - Nurse staffing patterns have come under increased scrutiny as hospital managers
      attempt to control costs without harming service quality or staff morale. This
      study presents production function results from a study of nurse output from 2002
      to 2005. The results suggest that productivity varies widely among the 39
      hospitals as a function of staffing patterns, methods of organization, and the
      degree of reliance on nurse extender technicians. Nurse extenders can enhance the
      marginal value product of the most educated nurses as the RNs concentrate their
      workday around patient care activities. The results suggest that nurse extenders
      free RNs from the burden of nonnursing tasks. Incentive pay for nurses based on
      productivity gains is associated with enhanced productivity. One should get the
      greatest output for the least input effort, better balancing all factors of
      service delivery to achieve the most with the smallest resource effort.

PMID- 19175233
TI  - The carriage trade trend.
AB  - The remarkable growth of the carriage trade movement in health care provision
      reflects the hyper-regulated health care environment that exists in health care
      today. This growth, which is only recently becoming noticed within the academic
      literature, is consistent with economic theory and is expected to continue.

PMID- 19175232
TI  - The company you keep: spreading effects of financial fraud on investor trust.
AB  - Investor trust is valuable to health care organizations. Without it, they may
      face higher capital costs. This study explores recent cases of fraud and the
      appearance of impropriety by health care organizations, focusing on the manners
      in which trust was violated, the systems that allowed those violations, and the
      effects on financial markets. Increases in the incidence and scale of such
      transgressions may be harbingers of worse times ahead. This article examines how
      recent events have affected the cost of capital, and what health care
      organizations can do to avoid being judged by the company they keep.

PMID- 19175234
TI  - Factors associated with lease financing in the hospital industry.
AB  - In contrast to capital leases, which are reported on the balance sheet as debt,
      operating leases are a form of off-balance sheet financing only reported in the
      notes to the financial statement and have limited disclosure requirements.
      Following the perpetuity method of corporate finance, this study developed a
      capitalized operating lease value for hospitals. Evaluating the substitutability
      between lease and debt financing, the findings show a marginal displacement of
      debt by lease financing. Assessing the relationship of market, mission,
      operating, and financial factors on lease financing for all short-term, acute
      care hospitals across the United States, the results indicate that investor-owned
      hospital management companies and hospitals located in CON markets are less
      likely to lease and that smaller hospitals with fewer unoccupied beds, higher
      proportion of government payers, low liquidity, and lower capital expenditures
      are more likely to lease.

PMID- 19175235
TI  - Fairness opinions in health care transactions--cause and effect: the emergence of
      private equity funds as a driving force in big and small transactions and the
      resulting increased use of fairness opinions.
AB  - The use of fairness opinions has become increasingly common with respect to the
      sale or merger of any company or division in a private equity funded or sponsored
      deal. The fairness opinion is often used to demonstrate that the value at which
      the transaction took place was a fair value to the selling company and thus did
      not improperly or unfairly leave the common holders with little consideration.
      This article covers rules and guidelines that should be adhered to in the
      issuance and review of fairness opinions.

PMID- 19175236
TI  - Demand matching: balancing cost and quality to maximize greatest postoperative
      outcomes.
AB  - Orthopedic hip and knee implant costs have risen 132 percent from 1991 to 2004,
      whereas reimbursements have only risen 16 percent. This increase is large, but
      the problem would not be as significant if reimbursement rates could compete with
      these increases. Medicare reimbursement has decreased 35 percent over the same
      time period. Health care professionals may not be able to change reimbursement
      methodologies, but we can offer cost-saving ideas to help balance out the
      equation. Although the primary purpose of demand matching is to improve implant
      selection based upon patient needs, it can also be used to help contain costs.

PMID- 19175237
TI  - The use of interest rate swaps by nonprofit organizations: evidence from
      nonprofit health care providers.
AB  - Although the use of derivatives, particularly interest rate swaps, has grown
      explosively over the past decade, derivative financial instrument use by
      nonprofits has received only limited attention in the research literature.
      Because little is known about the risk management activities of nonprofits, the
      impact of these instruments on the ability of nonprofits to raise capital may
      have significant public policy implications. The primary motivation of this study
      is to determine the types of derivatives used by nonprofits and estimate the
      frequency of their use among these organizations. Our study also extends
      contemporary finance theory by an empirical examination of the motivation for
      interest rate swap usage among nonprofits. Our empirical data came from 193 large
      nonprofit health care providers that issued debt to the public between 2000 and
      2003. We used a univariate analysis and a multivariate analysis relying on
      logistic regression models to test alternative explanations of interest rate
      swaps usage by nonprofits, finding that more than 45 percent of our sample, 88
      organizations, used interest rate swaps with an aggregate notional value in
      excess of $8.3 billion. Our empirical tests indicate the primary motive for
      nonprofits to use interest rate derivatives is to hedge their exposure to
      interest rate risk. Although these derivatives are a useful risk management tool,
      under conditions of falling bond market interest rates these derivatives may also
      expose a nonprofit swap user to the risk of a material unscheduled termination
      payment. Finally, we found considerable diversity in the informativeness of
      footnote disclosure among sample organizations that used interest rate swaps.
      Many nonprofits did not disclose these risks in their financial statements. In
      conclusion, we find financial managers in large nonprofits commonly use
      derivative financial instruments as risk management tools, but the use of
      interest rate swaps by nonprofits may expose them to other risks that are not
      adequately disclosed in their financial statements.

PMID- 19175238
TI  - The effect of interest rate derivative transactions on debt savings for not-for
      profit health systems.
AB  - The utilization of interest rate derivative instruments in US for-profit
      companies has grown exponentially since the early 1980s. International Swaps and
      Derivatives Association, Inc. (ISDA), reported that the amount of outstanding
      standard swaps grew by 25 percent during the first six months of 2003. The growth
      rate of all interest rate derivatives, which includes single-currency interest
      rate swaps, cross-currency interest rate swaps, and interest rate options, grew
      by 24 percent during the same period. The total outstanding amount of interest
      rate derivatives now totals $123.9 trillion compared to $99.9 trillion at the end
      of 2002 (Dodd, 2003). This explosion in usage is a testament to the efficacy and
      flexibility of the instruments and the increased appreciation by financial
      managers of the importance of financial risk management in a volatile interest
      rate environment.

PMID- 19175239
TI  - Trends in biopharmaceutical IPOS: 1996-2005.
AB  - This study examines the stock market reaction and other financial aspects of all
      biopharmaceutical firms that had an initial public offering (IPO) between 1996
      and 2005. Overall, increases in stock price at the close of the first day
      averaged 20.9 percent while the stock price of those firms that went public and
      survived until the end of 2005 stock price increased by only 7.7 percent on
      average. Sixty-nine percent of the firms that went public during this period were
      still trading at the end of 2005, with the majority of those de-listed being
      acquired or merged. Three-fourths of all biopharmaceutical IPOs had venture
      capital investors. Venture capitalists owned 47.4 percent of all common stock
      outstanding prior to the IPO on average.

PMID- 19175240
TI  - Did the strong get stronger and the weak get weaker? Examining changes in
      hospital financial condition.
AB  - In the late 1990s and early 2000s, many industry observers expressed the view
      that there was a growing dichotomy in the hospital industry in which financially
      weak hospitals were getting weaker and financially strong hospitals were getting
      stronger. Although existing analysis of cross-sectional financial data concur
      with this view, our analysis of 1993 to 2000 longitudinal data provides only
      partial support. We find that about one half of general acute care hospitals
      classified as financially strong in 1993-95 continued to be strong in 1998-00.
      More persistence was found for hospitals in weak financial position in 1993-95
      with about 60 to 70 percent of them continuing to be weak in 1998-00.
      Persistently weak hospitals did experience deteriorating financial condition
      whereas persistently strong hospitals appeared at best to hold their ground
      financially. Although many Medicare payment policies appear well-targeted to
      hospitals that would otherwise have financial problems (for example, isolated
      rural institutions and teaching hospitals), policymakers may need to consider the
      development of temporary loan or grant programs to assist hospitals that
      experience transitory financial problems during difficult times.

PMID- 19175241
TI  - Trends in Medicare disproportionate share (DSH) distribution in US hospitals:
      1996-2003.
AB  - Implemented in 1986, Medicare's disproportionate share (DSH) adjustment is
      intended to recognize hospitals' additional resource investment in caring for low
      income patients. This project analyzed changes in the DSH percentage between 1996
      and 2003 and examined the association between selected hospital characteristics
      and such changes. Results obtained revealed some interesting findings. First,
      minimal changes in DSH percentage occurred during the period 1996-1999 with a
      hike in that ratio in 2000-2001. However, even with the absence of any
      legislative or executive changes to the DSH threshold or formula during 2002 and
      2003, significant increases occurred during 2001-2003 (11 percent increase
      between 2001 and 2003). Such an increase may be caused by the nation's economic
      situation during that timeframe (i.e., more people depending on public programs
      for coverage).

PMID- 19175242
TI  - Predicting financial distress in teaching hospitals.
AB  - Despite the prestige and reputation of teaching hospitals, as a group they are in
      financial distress. If this trend continues, one would expect to see a higher
      incidence of mergers and acquisitions or divestitures of assets and services, and
      other strategies designed to combat failing businesses. Nearly one out of every
      six teaching hospitals sampled was predicted to be near immediate bankruptcy, and
      the overwhelming majority was not far behind. It will take a significant effort
      for these hospitals to continue to treat their operations as a clinical and
      research "business," but they must do just that if they are to survive the
      continually turbulent market.

PMID- 19175243
TI  - Research and under represented groups.

PMID- 19175244
TI  - African Americans and their distrust of the health care system: healthcare for
      diverse populations.
AB  - "To be used in some type of experiment and then be forgotten. Why are you
      interested in me now?" This is one of many sentiments felt by African Americans.
      In one of many surveys conducted by researchers, African Americans feared they
      would be used as guinea pigs for medical research. This survey also found that
      blacks were more likely than whites not to trust that their doctors would fully
      explain the significance of their participation in clinical research or other
      studies. Many scientists believe that bad feelings make it difficult for them to
      recruit minorities as participants in biomedical research studies in different
      areas. There continues to be an underlying element of mistrust between the poor
      populations and minority populations that may be subjects of research and the
      research establishment. The perception of mistrust from the African American
      community is in large caused by their previous experiences with the health care
      system. However, the mistrust is not only in perception, but has many other
      reasons. Mistrust of the health care system by African Americans is a major
      problem that has to be addressed and corrected. This paper is a historical
      perspective of the African Americans relating to their distrust of research and
      the traditional health care system.

PMID- 19175245
TI  - Consumer dissatisfaction, self-treatment, and health service use in low income
      African American and white older persons.
AB  - Differences in dissatisfaction with health care (problems with providers,
      geographic access and appointment availability), self-treating symptoms, personal
      health responsibility, and health service use were investigated in low income
      African American and White older persons. Data on these topics were collected
      from 103 African Americans and 101 Whites and analyzed using analysis of
      covariance and multiple regression. After controlling for variables that
      typically explain health service use, African Americans reported significantly
      more dissatisfaction with health care (p < .01) and greater personal health
      responsibility (p < .01) than Whites, but did not differ in the degree to which
      they self-treated or used health care. Significant predictors of health service
      use were declining health status and increasing levels of self-treatment for
      African Americans (R2 = .18) and declining health status and increasing age for
      Whites (R2 = 23).

PMID- 19175246
TI  - Prostate cancer community collaboration and partnership: education, awareness,
      recruitment, and outreach to southern African-American males.
AB  - Prostate cancer is a significant health problem for African-American men
      intensified by low participation in screenings, clinical trials, and prospective
      cohort studies. Ten focus groups were conducted with African-American males and
      their female partners/spouses. Perceptions and knowledge about prostate cancer,
      as well as willingness to participate in screening and research studies were
      measured. Participants had a basic level of knowledge about prostate cancer, and
      the importance of education was a unified theme. Dialogue with targeted African
      American men and their partners/spouses may increase awareness and retention in
      medical research, while influencing health promotion, education and behavior.

PMID- 19175247
TI  - Attitudes and beliefs about prostate cancer and screening among rural African
      American men.
AB  - PURPOSE: The research study purpose was to describe the personal attitudes and
      beliefs of rural African American men related to prostate cancer and screening.
      PROCEDURE: Audio taped interviews were conducted with nine (9) African American
      men living in rural communities of West Central Alabama. FINDINGS: Six common
      themes were found among the rural African American men participants. The themes
      identified were: (1) Disparity; (2) Lack of understanding; (3) Tradition; (4)
      Mistrust in the system; (5) Fear; and (6) Threat to manhood. CONCLUSIONS: The
      results support the general significance of understanding the views of the target
      population and specifically its culture and offer opportunities for adapting
      health promotion to the population.

PMID- 19175248
TI  - Recruitment and retention of older adults in influenza immunization study.
AB  - Minority older adults have been under-represented in previous research studies in
      which Caucasian populations have been recruited. This article describes a
      consumer-centered model that addresses strategies to enhance recruitment and
      retention of a racially diverse healthy elderly population in an influenza
      immunization study. A consumer-centered model was employed in a 3-year research
      study that examined age-related changes in the immune responses to influenza
      vaccination. Four factors seem to be critical for successful recruitment and
      retention of African American, Latino and Caucasian elders: (1) building trust
      between the research team, and the community at large; (2) convenience (or
      inconvenience) to the volunteer; (3) timing of recruitment and data collection;
      and (4) incentives.

PMID- 19175249
TI  - Self-advocacy in health care decision-making among elderly African Americans.
AB  - The purpose of this study was to identify factors that influence the self
      advocacy expressions of elderly African Americans. The sample consisted of 100
      elderly African Americans who responded to a series of questions about the
      characters in seven vignettes. Each vignette told a story about an elderly
      African American in a health care dilemma. The health care dilemma became more
      complex as the age of the main character increased. In addition, each participant
      completed the Multi-dimensional Health Locus of Control Scale and the
      Philadelphia Geriatric Morale Scale. Statistically significant differences were
      found between males and females and educational levels on the Powerful Others
      Subscale. A statistically significant relationship was found between high self
      advocacy expressions and marital status. Twenty-four percent (24.1%) of the
      participants rated as having high self-advocacy expressed dissatisfaction with
      their health status. The findings demonstrate some of the complexities involved
      in the study of elderly African Americans particularly related to the major
      impact of life experiences on their lives today.

PMID- 19175250
TI  - Health care provider and consumer understandings of cultural safety and cultural
      competency in health care: an Australian study.
AB  - There is increasing recognition in Australia that racial and ethnic minority
      groups experience significant disparities in health and health care compared with
      the average population and that the Australian health care system needs to be
      more responsive to the health and care needs of these groups. The paper presents
      the findings of a year long study that explored what providers and recipients of
      health care know and understand about the nature and implications of providing
      culturally safe and competent health care to minority racial and ethnic groups in
      Victoria, Australia. Analysis of the data obtained from interviewing 145
      participants recruited from over 17 different organizational sites revealed a
      paucity of knowledge and understanding of this issue and the need for a new
      approach to redress the status quo.

PMID- 19175251
TI  - On becoming aware of the less obvious.

PMID- 19175252
TI  - Carers' perceptions of pain in people with dementia: a grounded theory approach.
AB  - The purpose of this Grounded Theory based study was to add to the limited
      understanding about the perception and observation of pain by the formal and
      informal carers of people with dementia. Thirty-one carers talked about how they
      know when their person with dementia has pain. Findings showed there is no one
      set of signs or behaviours that indicate pain in all people with dementia.
      However, a common pain assessment process amongst carers involved being able to
      detect deviation from normal behaviours based upon their intimate knowledge of
      what is normal for their person. A central hypothesis was thus generated from the
      data that considered that effective pain assessment for people with dementia is
      dependent on carers having an intimate knowledge of the individual's normal state
      of being with dementia. Implications for nursing practice are discussed.

PMID- 19175253
TI  - Critical illness--a lived reality for patients and their families.
AB  - This case study tells of one family's experience surrounding the diagnosis of
      rare cancer, where both the medical system and family struggle with a critical,
      largely unknown illness. The experience was complicated by communication issues
      between the medical profession and family, support from counselling services, and
      lack of information--compounded by a health system concentrated in metropolitan
      areas.

PMID- 19175254
TI  - Evidenced based medicine. Benefits, limitations and issues for complementary and
      alternative medicine.
AB  - Evidence based medicine is examined in terms of its potential benefits and
      limitations. Currently randomised controlled trials are viewed as gold-standard
      evidence. It is argued that while this emphasis on clinical trials may have much
      value, other forms of evidence, especially in the field of complementary
      medicine, such as traditional use and consumer choice, may be appropriate. The
      NHMRC's (1999) Guidelines for Clinical Practice indicates that a range of
      evidence is acceptable in the creation and application of evidence based
      medicine. The Risk Society model with its emphasis on individualisation and
      scientific uncertainty is examined as a sociological framework that allows a
      greater consideration of 'other than science' knowledges in the evolution of
      evidence based health care.

PMID- 19175255
TI  - St John's wort: a prestigious 'weed'.
AB  - St John's wort first came to my attention while reading about treatment for
      Premenstrual Syndrome (PMS). The possibility of a herb being used successfully by
      many women for mild depression immediately sparked my interest. Until that time
      the closest I had been to natural therapies was to use vitamins. I had been
      educated that evidence-based treatment was the only definitive guide to health
      care, therefore I decided that further investigation was warranted prior to
      consulting a Herbalist. This article reveals the findings of my investigation.

PMID- 19175256
TI  - Pranic healing.
AB  - Pranic healing is a science and art of healing that treats the energy body, which
      interpenetrates and controls the physical body, mind and emotions. When Pranic
      healing is applied the molecular structure of liquid and dense states of matter
      can be altered significantly to create positive outcomes, as revealed through
      research.

PMID- 19175258
TI  - On endings and farewells.

PMID- 19175257
TI  - Alternative medicine and community-building.

PMID- 19175259
TI  - Facial expressions in paintings as perceived by the student nurse.
AB  - The aim of the study was to develop an educational tool consisting of selections
      of paintings in order to complement theoretical knowledge regarding non-verbal
      communication. Another aim was to investigate students' opinions of the
      educational tool. A visual art programme which introduced student nurses to
      varying facial expressions in art reproductions was developed as a complement to
      textbooks on nonverbal communication. Participants were student nurses from two
      nursing schools in Sweden. Data were collected over a period of two years (1998
      2000) in the second year of the 3-year undergraduate programme. Participants were
      able to infer whether a positive or negative message had been given to the
      depicted person. Participants' evaluations of the programme were expressed in
      positive terms.

PMID- 19175260
TI  - 'Moving on': the transition to living well with chronic illness.
AB  - This paper describes the process of 'moving on' when living with a chronic
      illness or condition. The findings of this study emerged from daily email
      conversations between six women who live with long term illness and the three
      researchers during a three month period in 2003. In collaboration with the women,
      researchers have drawn out seven interrelated themes which are seen to constitute
      the process of 'moving on'. The concept of readiness to change is discussed as
      fundamental to the relationship between potential learning as a result of living
      with illness and 'moving on'. We conclude that health workers are in a strong
      position to facilitate the learning that will assist people to 'move on' and
      incorporate illness as an ordinary part of life.

PMID- 19175261
TI  - Re-entering life: paediatric acute myeloid leukaemia at one year post treatment.
AB  - To date, there is scant psychosocial research on the experience of childhood AML.
      This article presents findings from the perspective of the child patients, their
      parents and siblings at one year post-treatment. The findings highlight
      challenges associated with re-entering life post-treatment with an emphasis on
      the ongoing sense of uncertainty, the changed sense of normalcy, and the
      difficulty of returning to the hospital for check-ups. A number of
      recommendations are made including the desirability of providing hospital space
      for check-ups away from the treatment area and the need for ongoing reassurance
      and support.

PMID- 19175262
TI  - Using Bowen technique in a health service workplace to improve the physical and
      mental wellbeing of staff.
AB  - A six week program using Bowen Technique treated 31 Hospital and Community Health
      Service staff in a group setting providing an innovative way to reduce stress and
      improve physical health. Quantitative and qualitative data indicated that Bowen
      Technique was successful in reducing pain, improving mobility, reducing stress,
      and improving energy, well being and sleep.

PMID- 19175263
TI  - Anthroposophical nursing.
AB  - Anthroposophical nursing evolved out of a striving to maintain the human caring
      and loving warmth of nursing practice whilst having cognisance of academic rigor
      and scientific nursing research. It is an extension of traditional nursing
      requiring inner personal development to accompany a modern scientific approach.

PMID- 19175264
TI  - On the gift of presence.

PMID- 19175265
TI  - The phenomenon of presence within contemporary nursing practice: a literature
      review.
AB  - Nursing practice underpinned by humanistic values may promote presence
      experiences within nurse-patient interactions. These interactions are powerful
      and beneficial both to nurse and patient. However, the phenomenon of presence is
      surrounded by competing and confused definitions. Whilst presence is arguably a
      core aspect of nursing practice, current health care environments significantly
      influence nurses' opportunities to experience presence.

PMID- 19175266
TI  - Factors shaping indigenous mental health: an ethnographic account of growing up
      Koori from a Gubba perspective.
AB  - This paper presents selected themes derived from stories provided by Aboriginal
      youth and adult community members during a doctoral research study. The study was
      conducted in an Aboriginal community in NSW, Australia. The ethnographic research
      was titled 'The development of mental health in Koori adolescents: Stories and
      memories from their youth'. The themes emerged from the data and provide a deeper
      insight into the notion of mental health from the perspective of the Aboriginal
      people in this study.

PMID- 19175267
TI  - Community mental health nurses and their emotional wellbeing: is anyone
      listening?
AB  - This paper highlights some of the findings from a recent study with women
      community mental health nurses which explored the relationship between emotional
      wellbeing and professional practice. Specifically, this article addresses the
      unique meaning of emotional wellbeing, self healing strategies used by
      participants, and identifies the relationship to professional practice. The
      findings revealed that the notion of emotional wellbeing whilst complex was
      explicitly linked to the iritertwining of their personal and professional
      experiences and situations. It is argued that the implications for failing to
      meet the needs of our nurses will not only jeopardise the nurses themselves but
      moreover the clients as recipients of such an essential service.

PMID- 19175268
TI  - Bowen technique--its use in work related injuries.
AB  - A program in Byron Shire in 2002 offered Health Service staff treatments with
      Bowen Technique. The program was evaluated after 9 months. The evaluation
      explored the effect of the treatment on work related injuries. The responses
      indicated that the provision of Bowen Therapy for staff might be an effective way
      of reducing Workcover claims.

PMID- 19175269
TI  - Could homeopathic medicine be utilised as a treatment for teething?
AB  - Despite much debate, teething is commonly believed to include a cluster of
      distressing symptoms. Over the centuries various treatments have been used and
      fallen into disrepute. Homeopathy has a track record of consistent and effective
      management of teething, treating the whole child regardless of the source of the
      distress. This article explores the literature on teething and calls for more
      research to be directed towards homeopathy's holistic approach towards managing
      teething symptoms.

PMID- 19175270
TI  - HypnoBirthing.

PMID- 19175271
TI  - On making the best of situations.

PMID- 19175272
TI  - Strategies for coping with spiritual pain: a comparison of insights from
      survivors and hospice patients.
AB  - The article presents recent findings on survivors' strategies for dealing with
      'spiritual pain'. The insights are compared to previously published data from the
      same study looking at hospice patients. The discussion provides nurses with
      insights to strategies used by survivors to cope with adjusting to life post
      treatment, how that differs from hospice patients, and the implication of such
      insights for nursing practice.

PMID- 19175273
TI  - Hope: metaphorically speaking.
AB  - In a recent Gadamerian hermeneutic study, photography and in-depth interviews
      were used as key methods to explicate the phenomenon of hope. Whilst using
      photography within qualitative research has become increasingly popular over the
      last decade, little has been written about how to introduce photographs as
      conversation enhancers or how photographs have the capacity to unleash both
      conceptual and linguistic metaphors. This article gives insights into the
      experience of using photographs to illuminate the phenomenon of hope and
      identifies metaphors that were revealed through the participants' photographs.

PMID- 19175274
TI  - The use of cranial osteopathy in the treatment of infants with breast feeding
      problems or sucking dysfunction.
AB  - Cranial osteopathy is gaining recognition as a successful treatment for a range
      of conditions, and has shown to be especially useful when dealing with instances
      of breastfeeding problems resulting from birth trauma. This paper explores the
      therapy in detail, its relationship to breastfeeding problems, raises suggestions
      as to how it could be applied to clinical practice, and outlines the need for
      further research.

PMID- 19175275
TI  - Therapeutic touch: the conventional versus the alternative.
AB  - Pain is a complex personal, subjective and unpleasant experience involving many
      sensations and perceptions and it has a profound impact on the well being of an
      individual, both physically and psychologically. With an increasing costs and
      pharmacological implications, many patients are beginning to look at alternative
      methods of pain relief. This paper reviews some issues in the use of Therapeutic
      Touch on pain management.

PMID- 19175276
TI  - Implementing reflexology into midwifery practice.
AB  - This paper reports on a small quantitative study of midwives who had undertaken a
      midwifery reflexology course in NSW, Australia. In particular, it examines some
      of the barriers and influences which affect implementing knowledge into practice.

PMID- 19175277
TI  - Facilitating dedication to spirit.

PMID- 19175278
TI  - Including the fathers' perspective in holistic care. Part 2: Findings on the
      fathers' hospital experience including restraining the child patient for
      treatment.
AB  - Part 2 of this discussion provides a detailed examination of specific issues
      associated with the fathers' personal involvement in their child's hospital
      treatment for paediatric acute lymphoblastic leukaemia (ALL). In particular,
      fathers testify to the difficulties they encounter when involved with the
      restraining of their child-patient for treatment. Issues raised by parents during
      this study have been addressed by recommendations detailing factors which need to
      be considered when providing holistic care for the family and the child with
      leukaemia.

PMID- 19175279
TI  - 'It's just the way I am': life with schizophrenia.
AB  - In this paper we focus on data generated from an in-depth interview with one
      participant of a larger study, and his voice in the participatory action research
      groups with other residents of a Supported Residential Facility. Bill describes
      what life is like when living with schizophrenia, being on anti-psychotic drugs
      and residing in boarding house accommodation. The aim of telling Bill's story is
      to reveal the burden of living with this mental illness and how it shapes every
      aspect of his world. We note that his physical health is neglected, and we
      conclude that residents such as Bill need assistance in health promotion, social
      engagement and navigating community and acute health services. Bill's story may
      contribute to sensitising health care professionals toward provision of holistic
      care and promote collaborative approaches focused toward addressing the needs
      identified for residents of boarding houses.

PMID- 19175280
TI  - An introduction to music and sound approaches for health professionals: overview
      of an undergraduate web-based nursing course.
AB  - Nursing educators have been constantly striving to develop a curriculum which
      enhances holistic patient care. In this article, a descriptive overview is given
      of a senior level, 3 credit, nursing course designed to provide nurses and other
      health professionals with a background in the uses of music and the importance of
      auditory environments for patient care and well-being. This course, which was
      developed by LeNavenec and Epstein, has been available via the internet since
      Spring 2003.

PMID- 19175281
TI  - Complementary therapies or 'luxury' therapies? A nurse's experience in the use of
      complementary therapies in nursing practice.
AB  - Complementary therapies have an increasing popularity. This case study explores
      the experience of a nurse who practises complementary therapies within the health
      care system where there is a still a widespread of skepticism within the medical
      profession. It is considered by the nurse that it is a 'luxury' to include these
      therapies in nursing practice.

PMID- 19175282
TI  - A personal conceptualization of healing.
AB  - Healing in itself is a complex issue, and to that regard this paper focuses on
      the concept through a whole person care approach. Emphasis is placed on providing
      a description of healing, identifying it's many attributes and contributing
      factors, and listing the qualities that define a holistic healer. Complementary
      therapies have been found to be a major contributor to holistic healing, though
      more importance needs to be placed on the idea that it is through an intentional
      change in thought processes, attitudes and practice that a nurse may experience
      contentment in the role of holistic healer.

PMID- 19175283
TI  - Simone's knees: phototherapy and pain.

PMID- 19175284
TI  - Mixed embryonal/alveolar rhabdomyosarcoma of the prostate: report of a case with
      molecular genetic studies and literature review.
AB  - Alveolar rhabdomyosarcoma (RMS) is 1 of 2 main subtypes of RMS in the pediatric
      age group and tends to occur in the extremities. The urogenital tract is another
      common site for RMS, but this typically involves the embryonal subtype including
      sarcoma botryoides. We report a 28-year-old male with a prostatic tumor that was
      excised en bloc and showed a RMS with separate areas of embryonal and solid
      alveolar morphologies at the light microscopic level. Both areas showed diffuse
      nuclear expression for myogenin, and both areas expressed the PAX3-FKHR fusion
      gene, a genetic change associated with alveolar but not embryonal RMS. A review
      of the literature documented only 5 cases of RMS primary to the prostate showing
      alveolar or mixed histology. Ours is the 6th case and the 1st with molecular
      findings. Although the diagnostic category of mixed embryonal/alveolar RMS
      remains in use, the nature of this type of RMS is incompletely understood. In our
      case, although the morphology was mixed embryonal/alveolar, at the genetic level
      this tumor was alveolar in nature.

PMID- 19175285
TI  - Explaining adherence success in sub-Saharan Africa: an ethnographic study.
AB  - BACKGROUND: Individuals living with HIV/AIDS in sub-Saharan Africa generally take
      more than 90% of prescribed doses of antiretroviral therapy (ART). This number
      exceeds the levels of adherence observed in North America and dispels early scale
      up concerns that adherence would be inadequate in settings of extreme poverty.
      This paper offers an explanation and theoretical model of ART adherence success
      based on the results of an ethnographic study in three sub-Saharan African
      countries. METHODS AND FINDINGS: Determinants of ART adherence for HIV-infected
      persons in sub-Saharan Africa were examined with ethnographic research methods.
      414 in-person interviews were carried out with 252 persons taking ART, their
      treatment partners, and health care professionals at HIV treatment sites in Jos,
      Nigeria; Dar es Salaam, Tanzania; and Mbarara, Uganda. 136 field observations of
      clinic activities were also conducted. Data were examined using category
      construction and interpretive approaches to analysis. Findings indicate that
      individuals taking ART routinely overcome economic obstacles to ART adherence
      through a number of deliberate strategies aimed at prioritizing adherence:
      borrowing and "begging" transport funds, making "impossible choices" to allocate
      resources in favor of treatment, and "doing without." Prioritization of adherence
      is accomplished through resources and help made available by treatment partners,
      other family members and friends, and health care providers. Helpers expect
      adherence and make their expectations known, creating a responsibility on the
      part of patients to adhere. Patients adhere to promote good will on the part of
      helpers, thereby ensuring help will be available when future needs arise.
      CONCLUSION: Adherence success in sub-Saharan Africa can be explained as a means
      of fulfilling social responsibilities and thus preserving social capital in
      essential relationships.

PMID- 19175286
TI  - The role of social capital in successful adherence to antiretroviral therapy in
      Africa.

PMID- 19175287
TI  - A 50-year-old man with deteriorating cognitive function and impaired movement.

PMID- 19175288
TI  - Rape in war is common, devastating, and too often ignored.

PMID- 19175289
TI  - A new look at some old animals.

PMID- 19175290
TI  - From creation to consolidation: a novel framework for memory processing.

PMID- 19175291
TI  - Concatenated analysis sheds light on early metazoan evolution and fuels a modern
      "urmetazoon" hypothesis.
AB  - For more than a century, the origin of metazoan animals has been debated. One
      aspect of this debate has been centered on what the hypothetical "urmetazoon"
      bauplan might have been. The morphologically most simply organized metazoan
      animal, the placozoan Trichoplax adhaerens, resembles an intriguing model for one
      of several "urmetazoon" hypotheses: the placula hypothesis. Clear support for a
      basal position of Placozoa would aid in resolving several key issues of metazoan
      specific inventions (including, for example, head-foot axis, symmetry, and
      coelom) and would determine a root for unraveling their evolution. Unfortunately,
      the phylogenetic relationships at the base of Metazoa have been controversial
      because of conflicting phylogenetic scenarios generated while addressing the
      question. Here, we analyze the sum of morphological evidence, the secondary
      structure of mitochondrial ribosomal genes, and molecular sequence data from
      mitochondrial and nuclear genes that amass over 9,400 phylogenetically
      informative characters from 24 to 73 taxa. Together with mitochondrial DNA genome
      structure and sequence analyses and Hox-like gene expression patterns, these data
      (1) provide evidence that Placozoa are basal relative to all other diploblast
      phyla and (2) spark a modernized "urmetazoon" hypothesis.

PMID- 19175292
TI  - Input subsidies to improve smallholder maize productivity in Malawi: toward an
      african green revolution.

PMID- 19175295
TI  - The publisher's pushback against NIH's public access and scholarly publishing
      sustainability.

PMID- 19175293
TI  - Neuropilin-1/GIPC1 signaling regulates alpha5beta1 integrin traffic and function
      in endothelial cells.
AB  - Neuropilin 1 (Nrp1) is a coreceptor for vascular endothelial growth factor A165
      (VEGF-A165, VEGF-A164 in mice) and semaphorin 3A (SEMA3A). Nevertheless, Nrp1
      null embryos display vascular defects that differ from those of mice lacking
      either VEGF-A164 or Sema3A proteins. Furthermore, it has been recently reported
      that Nrp1 is required for endothelial cell (EC) response to both VEGF-A165 and
      VEGF-A121 isoforms, the latter being incapable of binding Nrp1 on the EC surface.
      Taken together, these data suggest that the vascular phenotype caused by the loss
      of Nrp1 could be due to a VEGF-A164/SEMA3A-independent function of Nrp1 in ECs,
      such as adhesion to the extracellular matrix. By using RNA interference and
      rescue with wild-type and mutant constructs, we show here that Nrp1 through its
      cytoplasmic SEA motif and independently of VEGF-A165 and SEMA3A specifically
      promotes alpha5beta1-integrin-mediated EC adhesion to fibronectin that is crucial
      for vascular development. We provide evidence that Nrp1, while not directly
      mediating cell spreading on fibronectin, interacts with alpha5beta1 at adhesion
      sites. Binding of the homomultimeric endocytic adaptor GAIP interacting protein C
      terminus, member 1 (GIPC1), to the SEA motif of Nrp1 selectively stimulates the
      internalization of active alpha5beta1 in Rab5-positive early endosomes.
      Accordingly, GIPC1, which also interacts with alpha5beta1, and the associated
      motor myosin VI (Myo6) support active alpha5beta1 endocytosis and EC adhesion to
      fibronectin. In conclusion, we propose that Nrp1, in addition to and
      independently of its role as coreceptor for VEGF-A165 and SEMA3A, stimulates
      through its cytoplasmic domain the spreading of ECs on fibronectin by increasing
      the Rab5/GIPC1/Myo6-dependent internalization of active alpha5beta1. Nrp1
      modulation of alpha5beta1 integrin function can play a causal role in the
      generation of angiogenesis defects observed in Nrp1 null mice.

PMID- 19175296
TI  - Nanoparticle characteristics affecting environmental fate and transport through
      soil.
AB  - Nanoparticles are being used in broad range of applications; therefore, these
      materials probably will enter the environment during their life cycle. The
      objective of the present study is to identify changes in properties of
      nanoparticles released into the environment with a case study on aluminum
      nanoparticles. Aluminum nanoparticles commonly are used in energetic formulations
      and may be released into the environment during their handling and use. To
      evaluate the transport of aluminum nanoparticles, it is necessary not only to
      understand the properties of the aluminum in its initial state but also to
      determine how the nanoparticle properties will change when exposed to relevant
      environmental conditions. Transport measurements were conducted with a soil
      column system that delivers a constant upflow of a suspension of nanoparticles to
      a soil column and monitors the concentration, size, agglomeration state, and
      charge of the particles in the eluent. The type of solution and surface
      functionalization had a marked effect on the charge, stability, and agglomeration
      state of the nanoparticles, which in turn impacted transport through the
      receiving matrix. Transport also is dependent on the size of the nanoparticles,
      although it is the agglomerate size, not the primary size, that is correlated
      with transportability. Electrostatically induced binding events of positively
      charged aluminum nanoparticles to the soil matrix were greater than those for
      negatively charged aluminum nanoparticles. Many factors influence the transport
      of nanoparticles in the environment, but size, charge, and agglomeration rate of
      nanoparticles in the transport medium are predictive of nanoparticle mobility in
      soil.

PMID- 19175294
TI  - Hotspots of biased nucleotide substitutions in human genes.
AB  - Genes that have experienced accelerated evolutionary rates on the human lineage
      during recent evolution are candidates for involvement in human-specific
      adaptations. To determine the forces that cause increased evolutionary rates in
      certain genes, we analyzed alignments of 10,238 human genes to their orthologues
      in chimpanzee and macaque. Using a likelihood ratio test, we identified protein
      coding sequences with an accelerated rate of base substitutions along the human
      lineage. Exons evolving at a fast rate in humans have a significant tendency to
      contain clusters of AT-to-GC (weak-to-strong) biased substitutions. This pattern
      is also observed in noncoding sequence flanking rapidly evolving exons.
      Accelerated exons occur in regions with elevated male recombination rates and
      exhibit an excess of nonsynonymous substitutions relative to the genomic average.
      We next analyzed genes with significantly elevated ratios of nonsynonymous to
      synonymous rates of base substitution (dN/dS) along the human lineage, and those
      with an excess of amino acid replacement substitutions relative to human
      polymorphism. These genes also show evidence of clusters of weak-to-strong biased
      substitutions. These findings indicate that a recombination-associated process,
      such as biased gene conversion (BGC), is driving fixation of GC alleles in the
      human genome. This process can lead to accelerated evolution in coding sequences
      and excess amino acid replacement substitutions, thereby generating significant
      results for tests of positive selection.

PMID- 19175298
TI  - Quantitative evaluation of radiation damage to polyethylene terephthalate by soft
      X-rays and high-energy electrons.
AB  - The chemical changes and absolute rates in radiation damage to polyethylene
      terephthalate (PET) caused by soft X-rays and energetic electrons have been
      measured using a scanning transmission X-ray microscope (STXM). Electron beam
      damage at two different dose rates and a range of doses was performed in an 80
      keV transmission electron microscope (TEM). The STXM beam was used to create
      damage patterns with systematically varied doses of monochromatic soft X-rays on
      an adjacent piece of the same PET sample. NEXAFS spectroscopy at the C 1s and O
      1s edges was used to study the chemistry of the radiation damage and to determine
      quantitative critical doses for PET damage by both types of radiation. The
      spectral changes were similar for damage by electrons and X-rays, indicating the
      radiation chemistry is dominated by secondary processes, not the primary event.
      The critical dose for chemical changes determined from C 1s spectral features is
      4.2(6) x 10(8) Gy and was the same for soft X-rays and electrons within
      measurement uncertainties. The critical dose for specific damage processes (as
      defined by changes in several different, bond-specific spectral features) was
      found to be similar in the C 1s region and was comparable between C 1s and O 1s
      edges for electron beam damage. There were statistically different critical doses
      for soft X-ray damage as probed by changes in O 1s spectral features related to
      carbonyl and ester bonds.

PMID- 19175297
TI  - A transgenic strain of the nematode Caenorhabditis elegans as a biomonitor for
      heavy metal contamination.
AB  - Metallothionein (MT), a protein involved in metal regulation and detoxification,
      has been used widely as a biomarker of metal exposure. In the present study, a
      transgenic strain of the free-living soil nematode Caenorhabditis elegans was
      developed using the C. elegans MT-2 (mtl-2) promoter to control the transcription
      of green fluorescence protein (GFP) reporter. Response of this transgenic system
      to Cd, Hg, Cu, Zn, Ni, Pb, and As exposure in aquatic media was tested by
      quantifying GFP expression after 24 h of exposure. Response in Cd-spiked soil was
      tested in a similar manner. The mtl-2 transcription also was measured using real
      time reverse transcription-polymerase chain reaction to gain a mechanistic
      understanding of the transgene expression. Green fluorescence protein is induced
      by Cd, Hg, Cu, and Zn in a time- and concentration-dependent manner; mtl-2
      transcription is consistent with the GFP response. The minimum concentrations of
      Cd, Hg, Cu, and Zn that induce GFP response are 2- to 1000-fold lower than
      concentrations affecting traditional endpoints, such as lethality or behavioral
      change. The system responds to Cd in soil in a similar manner. Neither Ni nor Pb
      induces GFP, and neither induces mtl-2 transcription. Arsenic does not induce
      GFP, yet an increase in mtl-2 transcription was found, suggesting that As may
      interfere with GFP signaling. This mtl-2::GFP transgenic bioassay represents an
      alternative approach to quantify, both easily and quickly, a surrogate of MT in
      response to metal exposure (e.g., Cd, Hg, Cu, and Zn) in a variety of
      environments and potentially may be used for quantitative or
      semiquantitativebiomonitoring of metal contamination in soils and aquatic
      systems.

PMID- 19175299
TI  - Temperature of peptide ions generated by matrix-assisted laser desorption
      ionization and their dissociation kinetic parameters.
AB  - Product ion yields in postsource decay and photodissociation at 193 and 266 nm
      were measured for some peptide ions without a basic amino acid residue ([Y(6) +
      H](+), [F(5) + H](+), and [YPFVEPI + H](+)) generated by matrix-assisted laser
      desorption ionization (MALDI). Data indicated statistical nature for the
      dissociation processes. Assuming that peptide ions formed by MALDI are in thermal
      equilibrium at temperature T and that their dissociation rate constants are
      specified by the critical energy (E(0)) and entropy (DeltaS(double dagger)), a
      method based on kinetic analysis was devised to determine these parameters
      simultaneously. The matrix used was found to affect the effective temperature of
      peptide ions, 2,5-dihydroxybenzoic acid (400-430 K) < sinapinic acid (440 K) <
      alpha-cyano-4-hydroxycinnamic acid (460-510 K), in agreement with previous
      perceptions. E(0) of around 0.6 eV and DeltaS(double dagger) of -24 eu were
      smaller than previous quantum chemical results for small model peptide ions.

PMID- 19175300
TI  - Photophysical changes of pyranine induced by surfactants: evidence of premicellar
      aggregates.
AB  - We studied photophysical changes of pyranine in different surfactant environments
      using spectrophotometry, steady-state fluorescence, and time-resolved
      fluorescence lifetime. The effect of surfactants on such properties varied as a
      function of the surfactant charge. Whereas anionic surfactants did not show any
      kind of interaction, the nonionic surfactant Triton X-100 produced spectral
      changes in the dye, as a consequence of the shift of equilibrium between its
      excited species. In the case of fluorescence, these changes allowed the critical
      micellar concentration of the surfactant to be determined. However, the most
      important features were obtained from the interaction with cationic surfactants
      of the n-alkyl trimethylammonium bromides. Such interactions enabled the
      formation of premicellar aggregates to be determined. In addition, three or four
      critical concentrations could be defined, which were dependent on the length of
      the hydrocarbon chain. One of these was the critical micellar concentration of
      the surfactant. The remaining two or three were in the very dilute concentration
      domain from which several types of premicellar aggregates are formed. However,
      the interaction with dodecyltrimethylammonium bromide at submicellar
      concentrations evidenced a quenching effect of a different nature (either static
      or combined), depending on the surfactant concentration. By deconvoluting the
      overall pyranine fluorescence emission spectrum into a sum of overlapping
      Lorentzian-Gaussian functions, the principal microenvironments of the pyranine
      molecules can be ascertained. Fluorescence data are consistent with the location
      of pyranine in a variety of sites, including partitioning that may be influenced
      by electrostatic and pi-cation interactions in aqueous micelles.

PMID- 19175301
TI  - Theoretical study of the tautomerism, structures, and vibrational frequencies of
      the phosphaalkenes XP=C(CH3)2 (X = H, F, Cl, Br, OH, Ar(F) (Ar(F) = 2,6
      (CF3)2C6H3)).
AB  - Ab initio theoretical calculations have been used to study the influence of
      phosphorus substituents, Y, on the tautomerism between the vinylphosphine
      XP(H)C(CH(3))=CH(2) and the phosphaalkene XP=C(CH(3))(2) (X = H, F, Cl, Br, OH,
      and Ar(F); Ar(F) = 2,6-(CF(3))(2)C(6)H(3)) and on the acidity of the
      aforementioned vinylphosphine. The stabilization of the phosphaalkene and the
      increased acidity of the vinylphosphine by Ar(F) are possible factors in the
      successful synthesis of certain isolable phosphaalkenes. In this work, the
      properties of Ar(F) are assessed theoretically. Density functional theory using
      the B3LYP functional has been used for all substituents. In addition, coupled
      cluster singles and doubles with noniterative triples (CCSD(T)) has been used for
      X = H, F, Cl, Br, and OH. The phosphaalkene is favored over the vinylphosphine
      for all substituents, with F having the strongest stabilizing effect. Cl, Br, and
      OH have stronger stabilizing effects than Ar(F). In contrast, the most acidic
      vinylphosphine is that with Ar(F). To aid in the interpretation and analysis of
      future experimental work, CCSD(T) calculations were used to provide structures
      and vibrational frequencies for the series XP=C(CH(3))(2) (X = H, F, Cl, Br). The
      influence of the substituent on geometries and C=P and X-P stretching frequencies
      was examined, and comparisons were made with the CH(2)=PX series.

PMID- 19175302
TI  - Surface-enhanced Raman scattering: comparison of three different molecules on
      single-crystal nanocubes and nanospheres of silver.
AB  - We have investigated the surface-enhanced Raman scattering (SERS) of chemically
      prepared single-crystal nanocubes and nanospheres of Ag with three different
      molecules to quantitatively understand the effect of sharp features on the SERS
      enhancement factor. Both experimental measurements and theoretical calculations
      confirmed a higher SERS activity for the nanocubes as a result of sharp features
      on their surfaces. We also found major discrepancies between the measured SERS
      intensities and those predicted from the electromagnetic mechanism. Through
      analysis of SERS bands, we concluded that sharp features on the Ag nanocubes
      could greatly increase the contribution of the chemical enhancement to the SERS
      intensity.

PMID- 19175303
TI  - Photophysical studies on the noncovalent interaction of thioflavin T with
      cucurbit[n]uril macrocycles.
AB  - Noncovalent interaction of Thioflavin T (ThT) with versatile macrocyclic host
      molecules, namely, cucurbit[7]uril (CB7) and cucurbit[5]uril (CB5), has been
      investigated in aqueous solutions by photophysical methods. Steady-state and time
      resolved fluorescence studies illustrate significant enhancements/modifications
      in the ThT fluorescence yield, lifetime, and spectral features on interaction
      with the CBs and are assigned due to the formation of 1:1 and 2:1 complexes
      between the CBs and the ThT. The high binding constant values for the 1:1 complex
      (K(1) approximately 10(5) M(-1)) indicate the strong ion-dipole interaction
      between the host and guest molecules, whereas the 2:1 complex formation is mainly
      driven by weaker forces like hydrophobic interaction as evident from the lower
      binding constants (K(2) approximately 10(3) M(-1)). From the characteristic
      differences in the photophysical properties of the CB7-ThT and CB5-ThT complexes,
      it has been adjudged that ThT forms an inclusion complex with CB7 whereas with
      CB5, the interaction is through an exclusion complex formation. These contentions
      have been further verified by the rotational relaxation dynamics, NMR, and
      quantum chemical calculations on CB-ThT systems. The present results have also
      been compared with those reported for the dye in the presence of cyclodextrin
      hosts.

PMID- 19175304
TI  - Biodegradable nanoparticles based on linoleic acid and poly(beta-malic acid)
      double grafted chitosan derivatives as carriers of anticancer drugs.
AB  - Novel chitosan derivatives carrying linoleic acid (LA) as hydrophobic moieties
      and poly(beta-malic acid) (PMLA) as hydrophilic moieties (LA/PMLA double grafted
      chitosan, LMC) were synthesized. It self-assembled into nanoparticles of 190-350
      nm in water, which carried negative surface charges in physiological pH. The
      critical aggregation concentration of the LMC deceased with an increase in the LA
      content. Paclitaxel (PTX) was loaded into the LMC nanoparticles with a high
      loading efficiency and the maximum loading capacity of 9.9 +/- 0.4%. PTX-LMC
      nanoparticles exhibited a sustained release within 24 h in pH 7.4 phosphate
      buffered saline (PBS), and the release rate was affected by the LA content and
      PMLA length. Hemolysis and acute toxicity assessment indicated that the LMC
      nanoparticles were safe drug carriers for i.v. administration. Additionally, PTX
      LMC showed significantly potent tumor inhibition efficacy relative to that of
      TAXOL in S-180 bearing mice. Therefore, the LMC nanoparticles could be an
      effective and safe vehicle for systemic administration of hydrophobic drugs,
      especially PTX.

PMID- 19175305
TI  - Self-associating poly(ethylene oxide)-b-poly(alpha-cholesteryl carboxylate
      epsilon-caprolactone) block copolymer for the solubilization of STAT-3 inhibitor
      cucurbitacin I.
AB  - An increase in the degree of chemical compatibility between drug and polymeric
      structure in the core has been shown to raise the encapsulation efficiency and
      lower the rate of drug release from polymeric micelles. In this study, to achieve
      an optimized polymeric micellar delivery system for the solubilization and
      controlled delivery of cucurbitacin I (CuI), the Flory-Huggins interaction
      parameter (chi(sc)) between CuI and poly(epsilon-caprolactone) (PCL), poly(alpha
      benzylcarboxylate-epsilon-caprolactone) (PBCL) and poly(alpha-cholesteryl
      carboxylate-epsilon-caprolactone) (PChCL) structures was calculated by group
      contribution method (GCM) as an indication for the degree of chemical
      compatibility between different micellar core structures and CuI. The results
      pointed to a better compatibility between CuI and PChCL core rationalizing the
      synthesis of self-associating methoxy poly(ethylene oxide)-b-poly(alpha
      cholesteryl carboxylate-epsilon-caprolactone) block copolymer (MePEO-b-PChCL).
      Novel block copolymer of MePEO-b-PChCL was synthesized through, first,
      preparation of substituted monomer, that is, alpha-cholesteryl carboxylate
      epsilon-caprolactone, and further ring opening polymerization of this monomer by
      methoxy PEO (5000 g mol(-1)) using stannous octoate as catalyst. Synthesized
      block copolymers were characterized for their molecular weight and polydispersity
      by (1)H NMR and gel permeation chromatography. Self-assembled MePEO-b-PChCL
      micelles were characterized for their size, morphology, critical micellar
      concentration (CMC), capacity for the physical encapsulation of CuI, and mode of
      CuI release in comparison to MePEO-b-PCL and MePEO-b-PBCL micelles. Overall, the
      experimental order for the level of CuI encapsulation in different polymeric
      micellar formulations was consistent with what was predicted by the Flory-Huggins
      interaction parameter. Although MePEO-b-PChCL micelles exhibited the highest
      level of CuI loading, this structure did not show any significant superiority
      over MePEO-b-PCL in controlling CuI release. The most efficient control over the
      rate of CuI release was achieved by MePEO-b-PBCL micelles that had more viscous
      cores than that of MePEO-b-PChCL, instead. The results point to a potential for
      MePEO-b-PChCL micelles for the solubilization of cholesterol compatible drugs. It
      also highlights the inadequacy of the Flory-Huggins interaction parameter
      calculated by GCM in predicting the order of drug release from different
      polymeric micellar structures.

PMID- 19175306
TI  - Functional cell-based screening and saturation transfer double-difference NMR
      have identified haplosamate A as a cannabinoid receptor agonist.
AB  - A marine natural product extract library has been screened with a functional cell
      based G-protein coupled receptor assay to find compounds capable of binding the
      human cannabinoid receptors CB1 and CB2. The methanol extract of the marine
      sponge Dasychalina fragilis collected in Papua New Guinea was active in the
      assay. Bioassay-guided fractionation of the extract identified the phosphorylated
      sterol sulfate haplosamate A (1) as a cannabinoid receptor agonist. The high
      water solubility of haplosamate A (1) allowed exploration of its binding
      interactions with the human cannabinoid receptors in whole insect cells by means
      of saturation transfer double-difference NMR spectroscopy. This technique
      confirmed that haplosamate A (1) binds selectively to these receptors.

PMID- 19175307
TI  - Intrinsic Fano interference of localized plasmons in Pd nanoparticles.
AB  - Palladium (Pd) nanoparticles exhibit broad optical resonances that have been
      assigned to so-called localized surface plasmons (LSPs). The resonance's energy
      varies with particle shape in a similar fashion as is well known for LSPs in gold
      and silver nanoparticles, but the line-shape is always anomalously asymmetric. We
      here show that this effect is due to an intrinsic Fano interference caused by the
      coupling between the plasmon response and a structureless background originating
      from interband transitions. The conclusions are supported by experimental and
      numerical simulation data of Pd particles of different shape and
      phenomenologically analyzed in terms of the point dipole polarizability of
      spheroids. The latter analysis indicates that the degree of Fano asymmetry is
      simply linearly proportional to the imaginary part of the interband contribution
      to the metal dielectric function.

PMID- 19175308
TI  - Cleavage of four carbon-carbon bonds during biosynthesis of the griseorhodin a
      spiroketal pharmacophore.
AB  - The rubromycins, such as gamma-rubromycin, heliquinomycin, and griseorhodin A,
      are a family of extensively modified aromatic polyketides that inhibit HIV
      reverse transcriptase and human telomerase. Telomerase inhibition crucially
      depends on the presence of a spiroketal moiety that is unique among aromatic
      polyketides. Biosynthetic incorporation of this pharmacophore into the
      rubromycins results in a dramatic distortion of the overall polyketide structure,
      but how this process is achieved by the cell has been obscure. To identify the
      enzymes involved in spiroketal construction, we generated 14 gene-deletion
      variants of the griseorhodin A biosynthetic gene cluster isolated from the
      tunicate-associated bacterium Streptomyces sp. JP95. Heterologous expression and
      metabolic analysis allowed for an assignment of most genes to various stages of
      griseorhodin tailoring and pharmacophore generation. The isolation of the novel
      advanced intermediate lenticulone, which exhibits cytotoxic, antibacterial, and
      elastase-inhibiting activity, provided direct evidence that the spiroketal is
      formed by cleavage of four carbon-carbon bonds in a pentangular polyketide
      precursor. This remarkable transformation is followed by an epoxidation catalyzed
      by an unusual cytochrome P450/NADPH:ubiquinone oxidoreductase pair that utilizes
      a saturated substrate. In addition, the absolute configuration of griseorhodin A
      was determined by quantum-chemical circular dichroism (CD) calculations in
      combination with experimental CD measurements.

PMID- 19175309
TI  - Initial response of the potassium channel voltage sensor to a transmembrane
      potential.
AB  - Early transition events of the voltage sensor (VS) of Kv1.2 potassium channel
      embedded in a lipid membrane are triggered using full atomistic molecular
      dynamics (MD) simulations. When subject to an applied hyperpolarized
      transmembrane (TM) voltage, the VS undergoes conformational changes and reaches a
      stable kinetic intermediate state, beta', within 20 ns. The gating charge (
      approximately 2e) associated with this fast transition results mainly from salt
      bridge rearrangements involving negative charges in S2 and S3 and all but the two
      top residues R(294) and R(297) of S4. Interactions of the latter with
      phosphomoieties of the lipid head groups appear to stabilize the kinetic state
      beta'.

PMID- 19175310
TI  - Asymmetric C2-C3 cyclopentannulation of the indole ring.
AB  - Chiral nonracemic alkynyl(alkoxy)carbene complexes of tungsten(0) undergo the [3
      + 2] cyclization toward alpha-methylindoles and 1,6-dimethyl-1,2,3,4
      tetrahydropyridine to provide 2,3-indoline-fused cyclopentenone and 2,3
      piperidine-fused cyclopentenone skeletons, respectively, with very high
      enantiomeric purities (96-99% ee).

PMID- 19175311
TI  - Imaging single ZnO vertical nanowire laser cavities using UV-laser scanning
      confocal microscopy.
AB  - We report the fabrication and optical characterization of individual ZnO vertical
      nanowire laser cavities. Dilute nanowire arrays with interwire spacing >10 microm
      were produced by a modified chemical vapor transport (CVT) method yielding an
      ideal platform for single nanowire imaging and spectroscopy. Lasing
      characteristics of a single vertical nanowire are presented, as well as high
      resolution photoluminescence imaging by UV-laser scanning confocal microscopy. In
      addition, three-dimensional (3D) mapping of the photoluminescence emission
      performed in both planar and vertical dimensions demonstrates height-selective
      imaging useful for vertical nanowires and heteronanostructures emerging in the
      field of optoelectronics and nanophotonics.

PMID- 19175312
TI  - Examination of the biological role of the alpha(2-->6)-linked sialic acid in
      gangliosides binding to the myelin-associated glycoprotein (MAG).
AB  - The tetrasaccharide 1, a substructure of ganglioside GQ1b alpha, shows a
      remarkable affinity for the myelin-associated glycoprotein (MAG) and was
      therefore selected as starting point for a lead optimization program. In our
      search for structurally simplified and pharmacokinetically improved mimics of 1,
      modifications of the core disaccharide, the alpha(2-->3)- and the alpha(2-->6)
      linked sialic acid were synthesized. Biphenylmethyl and (S)-lactate were
      identified as suitable replacements for the alpha(2-->6)-linked sialic acid.
      Combined with a core modification and the earlier found aryl amide substituent in
      the 9-position of the alpha(2-->3)-linked sialic acid, high affinity MAG
      antagonists were identified. All mimics were tested in a competitive target-based
      binding assay, providing relative inhibitory potencies (rIP). Compared to the
      reference tetrasaccharide 1, the rIPs of the most potent antagonists 59 and 60
      are enhanced nearly 400-fold. Their K(D)s determined in surface plasmon resonance
      experiments are in the low micromolar range. These results are in
      semiquantitative agreement with molecular modeling studies. This new class of
      glycomimetics will allow to validate the role of MAG in the axon regeneration
      process.

PMID- 19175313
TI  - DNA mismatch binding and antiproliferative activity of rhodium metalloinsertors.
AB  - Deficiencies in mismatch repair (MMR) are associated with carcinogenesis. Rhodium
      metalloinsertors bind to DNA base mismatches with high specificity and inhibit
      cellular proliferation preferentially in MMR-deficient cells versus MMR
      proficient cells. A family of chrysenequinone diimine complexes of rhodium with
      varying ancillary ligands that serve as DNA metalloinsertors has been
      synthesized, and both DNA mismatch binding affinities and antiproliferative
      activities against the human colorectal carcinoma cell lines HCT116N and HCT116O,
      an isogenic model system for MMR deficiency, have been determined. DNA
      photocleavage experiments reveal that all complexes bind to the mismatch sites
      with high specificities; DNA binding affinities to oligonucleotides containing
      single base CA and CC mismatches, obtained through photocleavage titration or
      competition, vary from 10(4) to 10(8) M(-1) for the series of complexes.
      Significantly, binding affinities are found to be inversely related to ancillary
      ligand size and directly related to differential inhibition of the HCT116 cell
      lines. The observed trend in binding affinity is consistent with the
      metalloinsertion mode where the complex binds from the minor groove with ejection
      of mismatched base pairs. The correlation between binding affinity and targeting
      of the MMR-deficient cell line suggests that rhodium metalloinsertors exert their
      selective biological effects on MMR-deficient cells through mismatch binding in
      vivo.

PMID- 19175314
TI  - Dual labeled peptides as tools to study receptors: nanomolar affinity derivatives
      of TIPP (Tyr-Tic-Phe-Phe) containing an affinity label and biotin as probes of
      delta opioid receptors.
AB  - A general strategy for the design of dual labeled peptides was developed, and
      derivatives of the delta opioid receptor (DOR) selective antagonist TIPP (Tyr-Tic
      Phe-PheOH) containing both an affinity label and biotin were prepared by solid
      phase synthesis. Tyr-Tic-Phe-Phe(p-X)-Asp-NH(CH2CH2O)2-CH2CH2NH-biotin (where X =
      N=C=S or NHCOCH2Br) exhibit nanomolar DOR affinity. The ability to detect
      receptors labeled with these peptides following solubilization and SDS-PAGE
      demonstrate the applicability of this design approach for dual labeled peptide
      derivatives.

PMID- 19175315
TI  - Strategies for innovation in multicomponent reaction design.
AB  - By generating structural complexity in a single step from three or more
      reactants, multicomponent reactions (MCRs) make it possible to synthesize target
      compounds with greater efficiency and atom economy. The history of such reactions
      can be traced to the mid-19th century when Strecker first produced alpha
      aminonitriles from the condensation of aldehydes with ammonia and hydrogen
      cyanide. Recently, academic chemists have renewed their interest in MCRs. In
      part, the pharmaceutical industry has fueled this resurgence because of the
      growing need to assemble libraries of structurally complex substances for
      evaluation as lead compounds in drug discovery and development programs. The
      application of MCRs to that increasingly important objective remains limited by
      the relatively small number of such reactions that can be broadly applied to
      prepare biologically relevant or natural-product-like molecular frameworks. We
      were interested in applying logic-based approaches, such as our single reactant
      replacement (SRR) approach, as a way both to improve known MCRs and to design new
      multiple-component routes to bioactive structures. This Account provides several
      examples that illustrate the use of SRR with known MCRs as starting points for
      synthetic innovation in this area. As part of our working hypothesis, we
      initially explored strategies for engineering improvements into known MCRs,
      either by increasing the dimensionality--that is, changing an n-component to an
      (n + 1)-component reaction--or broadening the scope of useful input structures,
      or both. By exhaustively applying retrosynthetic analysis to the cognate MCR to
      identify and exploit alternative entry points into the overall reaction manifold,
      we have devised several such re-engineered MCRs. Serendipitous findings have also
      augmented the yield of useful developments from our logic-inspired approach. In
      some cases, we have identified surprising links between different compound
      families that provide useful new entry points for chemical library synthesis. In
      other cases, the same re-engineering logic made it possible (sometimes in
      unexpected ways) to transform certain nonelementary two-component reactions into
      higher order MCRs. While logic may also inspire the search for new MCRs, the
      design process requires added chemical creativity, which cannot be reduced to a
      simple formula. The long-term goal of our research is to expand the useful
      repertoire of such reactions, which are important as complexity-generating tools
      in both combinatorial and diversity-oriented synthesis.

PMID- 19175319
TI  - Novel indazole non-nucleoside reverse transcriptase inhibitors using molecular
      hybridization based on crystallographic overlays.
AB  - A major problem associated with non-nucleoside reverse transcriptase inhibitors
      (NNRTIs) for the treatment of HIV is their lack of resilience to mutations in the
      reverse transcriptase (RT) enzyme. Using structural overlays of the known
      inhibitors efavirenz and capravirine complexed in RT as a starting point, and
      structure-based drug design techniques, we have created a novel series of
      indazole NNRTIs that possess excellent metabolic stability and mutant resilience.

PMID- 19175321
TI  - Enhanced intersystem crossing in three-spin systems: a perturbation theory
      treatment.
AB  - We present a simple model for analyzing the spin dynamics of a three-spin system
      representing a photoexcited chromophore coupled to a stable radical species.
      Perturbation theory yields a Fermi's Golden Rule-type rate expression that
      describes the formation of a local triplet on the chromophore through spin
      exchange with the radical. The error introduced by perturbation theory is
      evaluated for a number of parameters. Finally, we explore the effect of different
      energetic and coupling parameters on the rate of triplet formation and suggest
      how this model can be used to tune the enhanced intersystem crossing in three
      spin systems.

PMID- 19175320
TI  - Discovery of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid
      hydrochloride (GAP-134)13, an orally active small molecule gap-junction modifier
      for the treatment of atrial fibrillation.
AB  - Rotigaptide (3) is an antiarrhythmic peptide that improves cardiac conduction by
      modifying gap-junction communication. Small molecule gap-junction modifiers with
      improved physical properties were identified from a Zealand Pharma peptide
      library using pharmaceutical profiling, established SAR around 3, and a putative
      pharmacophore model for rotigaptide. Activity of the compounds was confirmed in a
      mouse cardiac conduction block model of arrhythmia. Dipeptide 9f (GAP-134) was
      identified as a potent, orally active gap-junction modifier for clinical
      development.

PMID- 19175316
TI  - Effect of mutation of carboxyl side-chain amino acids near the heme on the
      midpoint potentials and ligand binding constants of nitrophorin 2 and its NO,
      histamine, and imidazole complexes.
AB  - Nitrophorins (NPs) are a group of NO-carrying heme proteins found in the saliva
      of a blood-sucking insect from tropical Central and South America, Rhodnius
      prolixus, the "kissing bug". NO is kept stable for long periods of time by
      binding it as an axial ligand to a ferriheme center. The fact that the
      nitrophorins are stabilized as Fe(III)-NO proteins is a unique property because
      most heme proteins are readily autoreduced by excess NO and bind NO to the Fe(II)
      heme irreversibly (K(d)s in the picomolar range). In contrast, the nitrophorins,
      as Fe(III) heme centers, have K(d)s in the micromolar to nanomolar range and thus
      allow NO to dissociate upon dilution following injection into the tissues of the
      victim. This NO can cause vasodilation and thereby allow more blood to be
      transported to the site of the wound. We prepared 13 site-directed mutants of
      three major nitrophorins, NP2, NP1, and NP4, to investigate the stabilization of
      the ferric-NO heme center and preservation of reversible binding that facilitates
      these proteins' NO storage, transport, and release functions. Of the mutations in
      which Glu and/or Asp were replaced by Ala, most of these carboxyls show a
      significant role stabilizing Fe(III)-NO over Fe(II)-NO, with buried E53 of NP2 or
      E55 of NP1 and NP4 being the most important and partially buried D29 of NP2 or
      D30 of NP4 being second in importance. The pK(a)s of the carboxyl groups studied
      vary significantly but all are largely deprotonated at pH 7.5 except E124.

PMID- 19175322
TI  - Synthesis and analysis of novel glycerolipids for the treatment of metabolic
      syndrome.
AB  - Tetradecylthioacetic acid (TTA) 1 is a peroxisome proliferator-activated receptor
      (PPAR) agonist found to improve insulin sensitivity, lower blood lipid levels,
      enhance fatty acid oxidation, and promote anti-inflammation in vivo. In an
      attempt to enhance these properties, two key thioether fatty acid (Thefa) lipids,
      ditetradecylthioacetyl phosphatidylcholine 2 and tritetradecylthioacetyl glycerol
      3, are synthesized and administered po to male Wistar rats at two different doses
      to study and compare metabolic outcomes relative to the administration of 1 alone
      after 6 days. Liposomal formulations of 1 and 2 are also prepared to evaluate
      acute metabolic responses (at 3 h) post i.v. injection. Across all metrics
      measured, 1-induced responses post po administration are in line with previous
      data. Responses induced from 3 are mostly equivalent to 1-induced responses. By
      contrast, 2-induced responses almost always outperform those of 1 and 3.
      Therefore, 2 may represent a new lead for the treatment of metabolic syndrome.

PMID- 19175323
TI  - Structural studies of langerin and Birbeck granule: a macromolecular organization
      model.
AB  - Dendritic cells, a sentinel immunity cell lineage, include different cell subsets
      that express various C-type lectins. For example, epidermal Langerhans cells
      express langerin, and some dermal dendritic cells express DC-SIGN. Langerin is a
      crucial component of Birbeck granules, the Langerhans cell hallmark organelle,
      and may have a preventive role toward HIV, by its internalization into Birbeck
      granules. Since langerin carbohydrate recognition domain (CRD) is crucial for HIV
      interaction and Birbeck granule formation, we produced the CRD of human langerin
      and solved its structure at 1.5 A resolution. On this basis gp120 high-mannose
      oligosaccharide binding has been evaluated by molecular modeling. Hydrodynamic
      studies reveal a very elongated shape of recombinant langerin extracellular
      domain (ECD). A molecular model of the langerin ECD, integrating the CRD
      structure, has been generated and validated by comparison with hydrodynamic
      parameters. In parallel, Langerhans cells were isolated from human skin. From
      their analysis by electron microscopy and the langerin ECD model, an
      ultrastructural organization is proposed for Birbeck granules. To delineate the
      role of the different langerin domains in Birbeck granule formation, we generated
      truncated and mutated langerin constructs. After transfection into a fibroblastic
      cell line, we highlighted, in accordance with our model, the role of the CRD in
      the membrane zipping occurring in BG formation as well as some contribution of
      the cytoplasmic domain. Finally, we have shown that langerin ECD triggering with
      a specific mAb promotes global rearrangements of LC morphology. Our results open
      the way to the definition of a new membrane deformation mechanism.

PMID- 19175324
TI  - Dendritic structure having a potential gradient: new synthesis and properties of
      carbazole dendrimers.
AB  - A new synthetic route for carbazole dendrimers was discovered using the copper
      catalyzed N-arylation reaction. This synthetic route allowed synthesizing the
      fourth generation carbazole dendrimer and several derivatives for the first time.
      The crystal structure, Mark-Houwink-Sakurada plots, and UV-vis and fluorescence
      studies showed that the dendritic carbazole backbone has a rigid and highly
      twisted structure. From the measurement of the redox potential of the ferrocene
      derivatives, the IR spectra of the benzophenone derivatives, and complexation
      behavior of the phenylazomethine derivatives, the inductive electron-withdrawing
      effect of the carbazole dendron was revealed. This suggested that the summation
      of this electron withdrawal from each layer may produce a potential gradient such
      that the outer layer is electron-rich and the inner layer is electron-poor in the
      carbazole dendron. By assignment of the (1)H and (13)C NMR spectra of the
      dendron, the existence of this kind of potential gradient was proved. Overall,
      these data show the pi-polarization substituent effect of the carbazole unit, and
      their summation determines the potential gradient in the repeating dendritic
      structure of the carbazole dendrimer.

PMID- 19175325
TI  - Structure and absolute configuration of the fungal ansabenzoquinone rhizopogone.
AB  - The main pigment of the basidiomycete Rhizopogon pumilionus is the
      [13]paracyclophane derivative rhizopogone (1). The structures of 1 and the
      accompanying 2-acetoxyrhizopogone (5) were determined by spectroscopic studies,
      including 1D and 2D NMR measurements. The absolute configuration of 1 was
      assigned by comparison of its CD spectrum with that of secotridentoquinone (4).
      The structures of 1 and tridentoquinone (3) suggest a common biosynthesis
      originating from 2-geranylgeranyl-6-hydroxy-1,4-benzoquinone (9). This supports
      the close taxonomic relationship of the genera Rhizopogon and Suillus
      (Boletales).

PMID- 19175328
TI  - Solid-phase synthesis of oligonucleotide conjugates useful for delivery and
      targeting of potential nucleic acid therapeutics.
AB  - Olignucleotide-based drugs show promise as a novel form of chemotherapy. Among
      the hurdles that have to be overcome on the way of applicable nucleic acid
      therapeutics, inefficient cellular uptake and subsequent release from endosomes
      to cytoplasm appear to be the most severe ones. Covalent conjugation of
      oligonucleotides to molecules that expectedly facilitate the internalization,
      targets the conjugate to a specific cell-type or improves the parmacokinetics
      offers a possible way to combat against these shortcomings. Since workable
      chemistry is a prerequisite for biological studies, development of efficient and
      reproducible methods for preparation of various types of oligonucleotide
      conjugates has become a subject of considerable importance. The present review
      summarizes the advances made in the solid-supported synthesis of oligonucleotide
      conjugates aimed at facilitating the delivery and targeting of nucleic acid
      drugs.

PMID- 19175329
TI  - Development and characterization of an aircraft aerosol time-of-flight mass
      spectrometer.
AB  - Vertical and horizontal profiles of atmospheric aerosols are necessary for
      understanding the impact of air pollution on regional and global climate. To gain
      further insight into the size-resolved chemistry of individual atmospheric
      particles, a smaller aerosol time-of-flight mass spectrometer (ATOFMS) with
      increased data acquisition capabilities was developed for aircraft-based studies.
      Compared to previous ATOFMS systems, the new instrument has a faster data
      acquisition rate with improved ion transmission and mass resolution, as well as
      reduced physical size and power consumption, all required advances for use in
      aircraft studies. In addition, real-time source apportionment software allows the
      immediate identification and classification of individual particles to guide
      sampling decisions while in the field. The aircraft (A)-ATOFMS was field-tested
      on the ground during the Study of Organic Aerosols in Riverside, CA (SOAR) and
      aboard an aircraft during the Ice in Clouds Experiment-Layer Clouds (ICE-L).
      Initial results from ICE-L represent the first reported aircraft-based single
      particle dual-polarity mass spectrometry measurements and provide an increased
      understanding of particle mixing state as a function of altitude. Improved ion
      transmission allows for the first single-particle detection of species out to
      approximately m/z 2000, an important mass range for the detection of biological
      aerosols and oligomeric species. In addition, high time resolution measurements
      of single-particle mixing state are demonstrated and shown to be important for
      airborne studies where particle concentrations and chemistry vary rapidly.

PMID- 19175330
TI  - Microwave-assisted synthesis of novel (5-nitropyridin-2-yl)alkyl and (5
      nitropyridin-3-yl)alkyl carbamates.
AB  - A straightforward approach to novel (5-nitropyridin-2-yl)alkyl and (5
      nitropyridin-3-yl)alkyl carbamate building blocks is presented in this study.
      Their construction is achieved by condensation of N-carbamate alpha- and beta
      amino carbonyl derivatives with 1-methyl-3,5-dinitro-2-pyridone 1 under microwave
      irradiation. Judiciously chosen modifications in the nature of the parent
      carbonyl starting material has influenced the regiochemical outcome of the
      reaction and allowed an efficient access to novel nitrogen-containing scaffolds.
      Compounds sharing morphological similarities have been gathered in three
      libraries differing from each other in a single structural parameter.

PMID- 19175332
TI  - Spectroscopy of protonated peptides assisted by infrared multiple photon
      excitation.
AB  - We report here a new technique for spectroscopic studies of protonated, gas-phase
      biomolecules and demonstrate its utility by measuring highly resolved electronic
      and infrared spectra of peptides of up to 17 amino acids. After UV excitation of
      an aromatic chromophore of a protonated peptide, a CO(2) laser further excites
      the molecules, increasing their vibrational energy and hence their dissociation
      rate, allowing detection of the UV excitation by monitoring the resulting
      photofragments. We show that addition of the CO(2) laser excitation increases the
      fragmentation yield on the time scale of our experiments by as much as 2 orders
      of magnitude, significantly enhancing the sensitivity of UV photofragment
      spectroscopy. We also demonstrate that this approach can be applied in an IR-UV
      double-resonance scheme, allowing measurement of conformer-specific infrared
      spectra of protonated peptides.

PMID- 19175331
TI  - Alpha anomers of iGb3 and Gb3 stimulate cytokine production by natural killer T
      cells.
AB  - Natural killer T cells (NKT cells) respond to presentation of specific
      glycolipids with release of a variety of proinflammatory and immunomodulatory
      cytokines. The repertoire of glycolipid antigens for these cells includes alpha
      glycosylceramides, alpha-glycosyldiacylglycerols, and the triglycosylceramide
      iGb3. Two features of iGb3 set it apart from these other antigens: (i) three
      sugars are required for stimulation and (ii) the glycosidic bond between ceramide
      and the proximal sugar is beta in iGb3, whereas it is alpha in other antigens. We
      have synthesized the alpha versions of iGb3 and Gb3 and demonstrate that they are
      effective antigens for NKT cells and that they do not require lysosomal
      processing to the monoglycosylceramides for stimulation. These
      triglycosylceramides constitute a new class of antigen that stimulates NKT cells
      comparably to monoglycosylceramides.

PMID- 19175333
TI  - Structures of hydrated Li+-thymine and Li+-uracil complexes by IRMPD spectroscopy
      in the N-H/O-H stretching region.
AB  - The interaction of lithium ions with two pyrimidine nucleobases, thymine and
      uracil, as well as the solvation of various complexes by one and two water
      molecules, has been studied in the gas phase. IRMPD spectra are reported for each
      of B-Li(+)-(H(2)O)(n) (n = 1-2) and B(2)-Li-(H(2)O)(m) (m = 0-1) for B = thymine,
      uracil over the 2500-4000 cm(-1) region. Calculations were performed using the
      B3LYP density functional in conjunction with the 6-31+G(d,p) basis set to model
      the vibrational spectra as well as MP2/6-311++G(2d,p) theory to model the
      thermochemistry of potential structures. Experimental and theoretical results
      were used in combination to determine structures of each complex, which are
      reported here. The lithium cation in all complexes was found to bond to the O4
      oxygen in both thymine and uracil, and the first two water molecules of solvation
      were found to bond to Li(+). The experimental spectra obtained for
      BLi(+)(H(2)O)(n) (n = 1-2) and B(2)Li(+) for thymine and uracil clearly resemble
      one another, suggesting similar structural features in terms of bonding between
      the base and Li(+), as well as for solvation. This was confirmed through
      theoretical work. The addition of water to the lithium ion-bound DNA base dimers
      has been shown to induce a significant change in structure of the dimer to a
      hydrogen-bonded system similar to base pairing in the Watson-Crick model of DNA.

PMID- 19175334
TI  - Rate coefficients for the gas-phase reactions of OH and NO3 radicals and O3 with
      ethyleneglycol monovinyl ether, ethyleneglycol divinyl ether, and
      diethyleneglycol divinyl ether.
AB  - Kinetic studies have been performed on the reactions of OH and NO(3) radicals and
      ozone with three ethyleneglycol vinyl ethers (EGVEs), that is, ethyleneglycol
      monovinyl ether (EGMVE, HOCH(2)CH(2)OCH=CH(2)), ethyleneglycol divinyl ether
      (EGDVE, H(2)C=CHOCH(2)CH(2)OCH=CH(2)), and diethyleneglycol divinyl ether
      (DEGDVE, H(2)C=CHOCH(2)CH(2)OCH(2)CH(2)OCH=CH(2)). Using a relative rate
      technique, rate coefficients have been determined for the reactions in a 405 L
      borosilicate glass chamber at (298 +/- 3) K in one atmosphere of synthetic air
      using in situ FTIR spectroscopy to monitor the reactants. The following rate
      coefficients (in units of cm(3) molecule(-1) s(-1)) were obtained: (1.04 +/-
      0.22) x 10(-10), (1.23 +/- 0.33) x 10(-10), and (1.42 +/- 0.30) x 10(-10) for the
      reaction of OH with EGMVE, EGDVE, and DEGDVE, respectively; (2.23 +/- 0.46) x 10(
      12), (1.95 +/- 0.50) x 10(-12), and (6.14 +/- 1.38) x 10(-12) for the reaction of
      NO(3) with EGMVE, EGDVE, and DEGDVE, respectively; and (2.02 +/- 0.41) x 10(-16),
      (1.69 +/- 0.41) x 10(-16), and (2.70 +/- 0.56) x 10(-16) for ozonolysis of EGMVE,
      EGDVE, and DEGDVE, respectively. Using the kinetic rate data, tropospheric
      lifetimes for EGMVE, EGDVE, and DEGDVE with respect to their reactions with OH,
      NO(3), and ozone have been estimated for typical ambient air concentrations of
      these oxidants.

PMID- 19175335
TI  - Deciphering chemical bonding in golden cages.
AB  - The recently developed adaptive natural density partitioning (AdNDP) method has
      been applied to a series of golden clusters. The pattern of chemical bonding in
      Au(20) revealed by AdNDP shows that 20 electrons form a four-center-two-electron
      (4c-2e) bond in each of 10 tetrahedral cavities of the Au(20) cluster. This
      chemical bonding picture can readily explain the tetrahedral structure of the
      Au(20) cluster. Furthermore, we demonstrate that the recovered 4c-2e bonds
      corresponding to independent structural fragments of the cluster provide
      important information about chemically relevant fragmentation of Au(20). In fact,
      some of these bonds can be removed from the initial tetrahedral structure
      together with the associated atomic fragments, leading to the family of smaller
      gold clusters. Chemical bonding in the systems formed in such a manner is yet
      closely related to the bonding in the parental systems showing persistence of the
      4c-2e bonding motif. Thus, the multicenter bonds in golden cages recovered by the
      AdNDP analysis correspond to the fragments that should be seen as building blocks
      of these chemical systems.

PMID- 19175336
TI  - What makes the huge 31P-31P coupling constants in S(PF2)2 and Se(PF2)2 vary so
      much with temperature?
AB  - The enormous temperature dependence of the (2)J(PP) coupling constants in
      S(PF(2))(2) and Se(PF(2))(2) has been explained by a theoretical investigation of
      their conformations and NMR coupling constants. In contrast, the coupling in
      O(PF(2))(2) is almost invariant. Gas electron diffraction data for S(PF(2))(2)
      have been reinterpreted. The results show that two conformers, with C(s) and
      C(2v) symmetry, exist for the S and Se compounds. The C(s) and C(2v) conformers
      have very different (2)J(PP) coupling constants (-12.6 and 395.2 Hz for
      S(PF(2))(2) at B3LYP/aug-cc-pVQZ) and thermal interconversion of these conformers
      explains the experimental behavior.

PMID- 19175338
TI  - Improving the point-charge description of hydrogen bonds by adaptive force
      matching.
AB  - The MP2f water force field, recently developed using the adaptive force matching
      method, is improved significantly after the introduction of a short-range
      repulsion term. This term is designed to address the deficiency of point-charge
      models at short charge-charge separations. It may also provide a more realistic
      description of hydrogen bonds by capturing exchange-repulsion interactions. When
      compared with MP2f, the new MP2f_hb force field predicts properties of liquid
      water in much better agreement with experiments. The calculated site-site radial
      distribution functions are in good agreement with X-ray diffraction data
      corroborating the argument that point-charge models with only Lennard-Jones
      repulsion underestimate the nearest neighbor O-O distance. The incorporation of
      the new short-range repulsion term is argued to be important for any force field
      model that uses point charges to model electrostatics.

PMID- 19175339
TI  - Building up nanotubes: docking of "Janus" cyclodextrins in solution.
AB  - Using molecular dynamics experiments, we analyze the association of "Janus" 6
      amino-6-deoxy-2O-carboxymethyl-beta-cyclodextrins (JCD) in aqueous solutions. In
      JCD dimers, the free energy associated with the primary-rim-secondary-rim docking
      shows a stable minimum of approximately -45 kcal mol(-1). Trimers in solution are
      also remarkably stable, exhibiting minimal distortions in their spatial and
      orientational distributions. The resulting geometrical docking shows the
      incipient characteristics of flexible nanotubes in solution, with eventual water
      interchange between the central channel and the bulk at the junctions between
      monomers. Structural and dynamical properties of the trapped water filling the
      nanotube are dictated to a large extent by the charge density at the rims.

PMID- 19175340
TI  - Two-photon polymerization of polydiacetylene.
AB  - We show that visible light can polymerize diacetylene monomers into
      polydiacetylene (PDA) in a two-photon process. We monitor the process by
      measuring Raman intensities of PDA using a Raman laser at 633 nm with variable
      intensity I and show that the Raman cross section at short times increases as I3,
      corresponding to a two-photon process. The process generates a relatively stable
      blue phase PDA, in contrast with UV polymerization that leads to a fast blue to
      red phase transformation.

PMID- 19175341
TI  - Chronoamperometric study of conformational relaxation in PPy(DBS).
AB  - In conjugated polymer devices that switch from one oxidation level to another,
      such as artificial muscles, it is important to understand memory effects that
      stem from conformational relaxation movements of the polymer chains.
      Chronoamperometry during electrochemical switching of polypyrrole doped with
      dodecylbenzenesulfonate, PPy(DBS), is used to gain insight into the
      conformational relaxation processes in cation-transporting materials. During
      oxidation, the current decays exponentially with a time constant that decreases
      with the anodic voltage. During reduction, there is again an exponentially
      decaying current with a time constant that decreases with the cathodic voltage,
      but superimposed on that is a small current peak that increases in size with the
      voltage. This peak accounts for a maximum of approximately 20% of the total
      reduction charge, which is approximately the same amount of charge that is in the
      most cathodic pair of peaks in the cyclic voltammogram. The position of this peak
      depends logarithmically on the applied cathodic potential (shifting to shorter
      times with larger Eca) as well as on the anodic potential that was applied just
      prior to the reduction step (shifting to longer times with Ean). Furthermore, the
      shoulder position depends logarithmically on the time that the prior anodic
      voltage was held (shifting to longer times with twait). These results are
      consistent with the electrochemically stimulated conformational relaxation (ESCR)
      model.

PMID- 19175342
TI  - Molecular dynamics study of poly(diallyldimethylammonium chloride)
      (PDADMAC)/sodium dodecyl sulfate (SDS)/decanol/water systems.
AB  - We have performed a 50 ns of molecular dynamics study of
      poly(diallyldimethylammonium chloride) (PDADMAC)/sodium dodecyl sulfate
      (SDS)/decanol/water systems. The influence of the cationic polyelectrolyte on the
      anionic SDS-based lamellar liquid crystalline system was investigated. The main
      structural parameters have been calculated and compared with experimental data.
      We obtain two types of PDADMAC conformation, a more folded structure A and a
      structure B where the PDADMAC molecule is adsorbed at the anionic head groups of
      the surfactant molecules. The polyelectrolyte-induced coexistence of two lamellar
      phases at a concentration of 2-3% of PDADMAC is observed, which is in agreement
      with experimental findings.

PMID- 19175343
TI  - Increasing the trapping efficiency of particles in microfluidic planar platforms
      by means of negative dielectrophoresis.
AB  - We present a novel planar electrode geometry in which particles (typically 10
      microm in diameter) are focused near a defined surface before being trapped using
      negative dielectrophoresis. The focusing element can deflect particles having
      speeds up to hundreds of micrometers per second. This trapping configuration
      results in improved trapping yields and a decrease in overall reagent
      consumption. Particles are trapped dynamically while flowing in a microfluidic
      channel.

PMID- 19175344
TI  - Small-molecule binding at an abasic site of DNA: strong binding of lumiflavin for
      improved recognition of thymine-related single nucleotide polymorphisms.
AB  - The binding behavior of lumiflavin, a biologically vital ligand, with DNA
      duplexes containing an abasic (AP) site and various target nucleobases opposite
      the AP site is studied. Lumiflavin binds selectively to thymine (T) opposite the
      AP site in a DNA duplex over other nucleobases. Using 1H NMR spectroscopy and
      fluorescence measurements, we show that ligand-DNA complexation takes place by
      hydrogen-bond formation between the ligand and the target nucleobases and by
      stacking interactions between the ligand and the nucleobases flanking the AP
      site. From isothermal titration calorimetric experiments, we find that ligand
      incorporation into the AP sites is primarily enthalpy-driven. Examination of
      ionic strength dependency of ligand binding with DNA reveals that ligand-DNA
      complexation is a manifestation of both electrostatic and nonelectrostatic
      interactions and that the contribution from the nonelectrolyte effect is
      fundamental for the stabilization of the ligand-DNA complex. In comparison to
      riboflavin, reported previously as a T-selective ligand, lumiflavin binds to the
      DNA much more strongly and is a more promising ligand for efficient detection of
      T-related single nucleotide polymorphisms.

PMID- 19175345
TI  - A new approach to neuraminic acid analogues via 1,2-oxazines.
AB  - A new stereoselective and potentially very flexible (C(5) + C(3) + C(1)) approach
      to neuraminic acid derivatives and analogues has been established using
      enantiopure nitrones and alkoxyallenes as C(3) and C(1) building blocks.
      Substituent OR(2) in position 4 of neuraminic acid analogues is defined by the
      alkoxyallene employed for the synthesis of the intermediate 1,2-oxazine. Side
      chain R(1) can be varied by using different precursor nitrones and introduction
      of different protection groups R(3) at the amino function is also possible.

PMID- 19175346
TI  - Facile synthesis of 2-O-iodoacetyl protected glycosyl iodides: useful precursors
      of 1-->2-linked 1,2-trans-glycosides.
AB  - The preparation and utilization of novel iodide glycosyl donors, 2-O-iodoacetyl
      glycopyranosyl iodides, is described. The mechanism for the reaction of iodine
      with carbohydrate cyclic ketene acetal was investigated through low-temperature
      NMR experiments. 2-O-Iodoacetyl-glycopyranosyl iodides can serve as effective
      glycosyl donors giving 2-O-iodoacetyl 1,2-trans-glycosides in high yields and
      excellent stereoselectivities. The 2-O-iodoacetyl group was removed selectively
      with thiourea to afford 2-hydroxy 1,2-trans-glycosides in high yield without
      affecting other protecting groups and anomeric configurations.

PMID- 19175348
TI  - An efficient method for construction of the angularly fused 6,3,5-tricyclic
      skeleton of mycorrhizin A and its analogues.
AB  - The angularly fused 6,3,5-tricyclic system is readily generated via a cascade
      cyclization under acid promotion. The reaction proceeds at room temperature with
      high stereochemical fidelity from the electrophilic center of the epoxide to the
      cyclopropane product. This methodology provides a potentially useful approach for
      the synthesis of mycorrhizin A and its analogues.

PMID- 19175347
TI  - Design of a bisamidinium claisen rearrangement catalyst for monodentate
      substrates.
AB  - A bisamidinium catalyst has been designed for the Claisen rearrangement. The
      primary design feature is a dual hydrogen bonding array that can coordinate a
      singular oxygen atom of the substrate. The ability to function as a dual hydrogen
      donor is key as the bisamidinium accelerates the Claisen rearrangement to a
      greater extent than Bronsted acids with lower pK(a) values.

PMID- 19175349
TI  - Stereodivergency of triazolium and imidazolium-derived NHCs for catalytic,
      enantioselective cyclopentane synthesis.
AB  - Chiral triazolium- and imidazolium-derived N-heterocyclic carbene catalysts
      promote the direct annulation of alpha,beta-unsaturated aldehydes and achiral
      alpha-hydroxy enones to afford cyclopentane-fused lactones with high
      enantioselectivity. Remarkably, otherwise structurally identical imidazolium and
      triazolium precatalysts afford different major products. These studies provide
      both an efficient entry to valuable chiral structures and a dramatic
      demonstration of stereodivergency of chiral imidazolium versus triazolium-derived
      N-heterocyclic carbene catalysts.

PMID- 19175351
TI  - Total synthesis of (+)-azinothricin and (+)-kettapeptin.
AB  - Asymmetric total syntheses of (+)-azinothricin and (+)-kettapeptin have been
      completed through a common new pathway that exploits a highly chemoselective
      coupling reaction between the fully elaborated cyclodepsipeptide 5 and the glycal
      activated esters 3 and 4 at the final stages of both respective syntheses.

PMID- 19175350
TI  - Asymmetric bisboranes as bidentate catalysts for carbonyl substrates.
AB  - A new class of C(2) symmetric bisoxazaborolidinone compounds is described which
      exhibits bidentate binding to carbonyl substrates. Using the Diels-Alder reaction
      as a model system, the catalytic activity of these bis-Lewis acids is probed.
      Reaction rates and selectivities are observed that are higher than the
      corresponding mono-Lewis acids. This novel system offers a potentially powerful
      new approach to asymmetric Lewis acid catalysis.

PMID- 19175353
TI  - High ortho preference in Ni-catalyzed cross-coupling of halophenols with alkyl
      grignard reagents.
AB  - High preference of substitution at the position ortho to the hydroxy group was
      observed for Ni-catalyzed cross-coupling reactions of dihalophenols with alkyl
      Grignard reagents. Reactions of 2,4-dihalophenols, with various combinations of
      F, Cl, and Br, were shown to afford ortho-cross-coupled products selectively. In
      addition, high ortho preference was also observed in competitive cross-coupling
      reactions between 2-halophenols and other halophenols.

PMID- 19175352
TI  - Synthesis of A83586C analogs with potent anticancer and beta-catenin/
      TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs
      and pRb.
AB  - The synthesis of three potent new antitumor agents is described: the A83586C
      citropeptin hybrid (1), the A83586C-GE3 hybrid (2), and l-Pro-A83586C (3).
      Significantly, compounds 1 and 2 function as highly potent inhibitors of beta
      catenin/TCF4 signaling within cancer cells, while simultaneously downregulating
      osteopontin (Opn) expression. A83586C antitumor cyclodepsipeptides also inhibit
      E2F-mediated transcription by downregulating E2F1 expression and inducing
      dephosphorylation of the oncogenic hyperphosphorylated retinoblastoma protein
      (pRb).

PMID- 19175354
TI  - Catalytic, nucleophilic allylation of aldehydes with allyl acetate.
AB  - A new catalytic allylation of aldehydes has been developed that employs allyl
      acetate as the allylating reagent. Under catalysis by ruthenium trichloride (3
      mol %) in the presence of carbon monoxide (30 psi), water (1.5 equiv), and
      triethylamine (0.1 equiv), a wide range of aromatic, olefinic, and aliphatic
      aldehydes are efficiently allylated under mild conditions (70 degrees C, 24-48
      h). The stoichiometric byproducts of this reaction are carbon dioxide and acetic
      acid.

PMID- 19175355
TI  - The protective effects of exercise and phosphoinositide 3-kinase (p110alpha) in
      the failing heart.
AB  - Despite the development of a wide range of therapies, heart failure remains a
      leading cause of death in Western society. New therapies are needed to help
      combat this debilitating condition. Exercise is becoming an increasingly
      important feature of rehabilitation programmes for patients with heart failure.
      Before the 1980s, patients with heart failure were advised not to exercise as it
      was thought that exercise would increase the risk of a cardiac event (such as
      myocardial infarction). However, in recent years both aerobic and resistance
      training have been shown to be safe and beneficial for patients with heart
      failure, improving exercise tolerance and quality of life, and preventing
      muscular deconditioning. The molecular mechanisms responsible for exercise
      induced cardioprotection are yet to be elucidated, however studies in transgenic
      mice have identified PI3K(p110alpha) (phosphoinositide 3-kinase p110alpha) as a
      likely mediator. PI3K(p110alpha) is a lipid kinase which is activated in the
      heart during chronic exercise training, and is important for maintaining heart
      structure and function in various pathological settings. In the present review
      the protective effects of PI3K(p110alpha) in the failing heart and its potential
      as a therapeutic strategy for the treatment of heart failure is discussed.

PMID- 19175356
TI  - Cellular and molecular effects of mechanical stretch on vascular cells and
      cardiac myocytes.
AB  - Cells in the cardiovascular system are permanently subjected to mechanical forces
      due to the pulsatile nature of blood flow and shear stress, created by the
      beating heart. These haemodynamic forces play an important role in the regulation
      of vascular development, remodelling, wound healing and atherosclerotic lesion
      formation. Mechanical stretch can modulate several different cellular functions
      in VSMCs (vascular smooth muscle cells). These functions include, but are not
      limited to, cell alignment and differentiation, migration, survival or apoptosis,
      vascular remodelling, and autocrine and paracrine functions. Laminar shear stress
      exerts anti-apoptotic, anti-atherosclerotic and antithrombotic effects on ECs
      (endothelial cells). Mechanical stretch of cardiac myocytes can modulate growth,
      apoptosis, electric remodelling, alterations in gene expression, and autocrine
      and paracrine effects. The aim of the present review is primarily to summarize
      the cellular and molecular effects of mechanical stretch on vascular cells and
      cardiac myocytes, emphasizing the molecular mechanisms underlying the regulation.
      Knowledge of the impact of mechanical stretch on the cardiovascular system is
      vital to the understanding of the pathogenesis of cardiovascular diseases, and is
      also crucial to provide new insights into the prevention and therapy of
      cardiovascular diseases.

PMID- 19175357
TI  - RGS proteins: identifying new GAPs in the understanding of blood pressure
      regulation and cardiovascular function.
AB  - Understanding the mechanisms that underlie BP (blood pressure) variation in
      humans and animal models may provide important clues for reducing the burden of
      uncontrolled hypertension in industrialized societies. High BP is often
      associated with increased signalling via G-protein-coupled receptors. Three
      members of the RGS (regulator of G-protein signalling) superfamily RGS2, RGS4 and
      RGS5 have been implicated in the attenuation of G-protein signalling pathways in
      vascular and cardiac myocytes, as well as cells of the kidney and autonomic
      nervous system. In the present review, we discuss the current state of knowledge
      regarding their differential expression and function in cardiovascular tissues,
      and the likelihood that one or more of these alleles are candidate hypertension
      genes. Together, findings from the studies described herein suggest that
      development of methods to modulate the expression and function of RGS proteins
      may be a possible strategy for the treatment and prevention of hypertension and
      cardiovascular disease.

PMID- 19175358
TI  - Transient limb ischaemia remotely preconditions through a humoral mechanism
      acting directly on the myocardium: evidence suggesting cross-species protection.
AB  - rIPC (remote ischaemic preconditioning) is a phenomenon whereby short periods of
      ischaemia and reperfusion of a tissue or organ (e.g. mesentery, kidney) can
      protect a distant tissue or organ (e.g. heart) against subsequent, potentially
      lethal, ischaemia. We, and others, have shown that transient limb ischaemia can
      provide potent myocardial protection experimentally and clinically during cardiac
      surgery. Nonetheless, our understanding of the signal transduction from remote
      stimulus to local effect remains incomplete. The aim of the present study was to
      define the humoral nature of rIPC effector(s) from limb ischaemia and to study
      their local effects in isolated heart and cardiomyocyte models. Using a
      Langendorff preparation, we show that infarct size after coronary artery ligation
      and reperfusion was substantially reduced by rIPC in vivo, this stimulus up
      regulating the MAPKs (mitogen-activating protein kinases) p42/p44, and inducing
      PKCepsilon (protein kinase Cepsilon) subcellular redistribution. Pre-treatment
      with the plasma and dialysate of plasma (obtained using 15 kDa cut-off dialysis
      membrane) from donor rabbits subjected to rIPC similarly protected against
      infarction. The effectiveness of the rIPC dialysate was abrogated by passage
      through a C18 hydrophobic column, but eluate from this column provided the same
      level of protection. The dialysate of rIPC plasma from rabbits and humans was
      also tested in an isolated fresh cardiomyocyte model of simulated ischaemia and
      reperfusion. Necrosis in cardiomyocytes treated with rIPC dialysate was
      substantially reduced compared with control, and was similar to cells pre-treated
      by 'classical' preconditioning. This effect, by rabbit rIPC dialysate, was
      blocked by pre-treatment with the opiate receptor blocker naloxone. In
      conclusion, in vivo transient limb ischaemia releases a low-molecular-mass (<15
      kDa) hydrophobic circulating factor(s) which induce(s) a potent protection
      against myocardial ischaemia/reperfusion injury in Langendorff-perfused hearts
      and isolated cardiomyocytes in the same species. This cardioprotection is
      transferable across species, independent of local neurogenic activity, and
      requires opioid receptor activation.

PMID- 19175359
TI  - Serial changes in adiponectin and BNP in ACS patients: paradoxical associations
      with each other and with prognosis.
AB  - Plasma adiponectin is inversely associated with the risk of coronary heart
      disease in healthy people. However, adiponectin and BNP (B-type natriuretic
      peptide) are both known to be positively associated with a risk of poor outcome,
      and with each other, in ACS (acute coronary syndrome) patients. Serial changes in
      plasma adiponectin and BNP following ACS have not been assessed previously, and
      may clarify these apparently paradoxical associations. In the present study,
      adiponectin, BNP, classical risk markers and clinical parameters were measured in
      plasma from 442 consecutive ACS patients in an urban teaching hospital, with
      repeat measures at 7 weeks (n=338). Patients were followed-up for 10 months. Poor
      outcome was defined as mortality or readmission for ACS or congestive heart
      failure (n=90). In unadjusted analysis, the change in adiponectin (but not
      baseline or 7-week adiponectin) was significantly associated with the risk of an
      adverse outcome {odds ratio (OR), 5.42 [95% CI (confidence interval), 2.78
      10.55]}. This association persisted after adjusting for classical risk factors
      and clinical markers, but was fully attenuated by adjusting for the 7-week BNP
      measurement [OR, 1.13 (95% CI, 0.27-4.92)], which itself remained associated with
      risk [OR, 5.86 (95% CI, 1.04-32.94)]. Adiponectin and BNP positively correlated
      at baseline and 7 weeks, and the change in both parameters over 7 weeks also
      correlated (r=0.39, P<0.001). In conclusion, increases in plasma adiponectin
      (rather than absolute levels) after ACS are related to the risk of an adverse
      outcome, but this relationship is not independent of BNP levels. The results of
      the present study allude to a potential direct or indirect relationship between
      adiponectin and BNP post-ACS which requires further investigation.

PMID- 19175360
TI  - Proper expression of helix-loop-helix protein Id2 is important to chondrogenic
      differentiation of ATDC5 cells.
AB  - The process of chondrogenesis can be mimicked in vitro by insulin treatment of
      mouse ATDC5 chondroprogenitor cells. To identify novel factors that are involved
      in the control of chondrogenesis, we carried out a large-scale screening through
      retroviral insertion mutagenesis and isolated a fast-growing ATDC5 clone
      incapable of chondrogenic differentiation. Inverse-PCR analysis of this clone
      revealed that the retroviral DNA was inserted into the promoter region of mouse
      Id2 (inhibitor of DNA-binding protein 2) gene. This retroviral insertion
      increased Id2 protein levels to twice those found in normal ATDC5 cells. To
      investigate whether an elevated level of Id2 protein was responsible for
      inhibition of chondrogenic differentiation, ATDC5 cells were infected with a
      retrovirus to stably express Id2. ATDC5 cells expressing ectopic Id2 exhibited
      signs of de-differentiation, such as rapid growth, and insulin failed to induce
      expression of Sox9 (Sry-type high-mobility-group box 9) or matrix genes such as
      type II collagen (COL2) in these cells. When endogenous Id2 was knocked down by
      siRNA (small interfering RNA) in ATDC5 cells, expression of Sox9 and COL2 was
      increased and chondrogenic differentiation was accelerated. To examine how Id2 is
      expressed in chondrocytes in vivo, we carried out immunostaining of E16.5 mouse
      embryos and found that Id2 is expressed in articular chondrocytes and
      proliferating chondrocytes, but barely detectable in hypertrophic chondrocytes.
      Our results suggest that proper expression of Id2 is important to achieving a
      fine balance between growth and differentiation during chondrogenesis.

PMID- 19175361
TI  - Structural and functional characterization of SplA, an exclusively specific
      protease of Staphylococcus aureus.
AB  - Staphylococcus aureus is a dangerous human pathogen whose antibiotic resistance
      is steadily increasing and no efficient vaccine is as yet available. This serious
      threat drives extensive studies on staphylococcal physiology and pathogenicity
      pathways, especially virulence factors. Spl (serine protease-like) proteins
      encoded by an operon containing up to six genes are a good example of poorly
      characterized secreted proteins probably involved in virulence. In the present
      study, we describe an efficient heterologous expression system for SplA and
      detailed biochemical and structural characterization of the recombinant SplA
      protease. The enzyme shares a significant sequence homology to V8 protease and
      epidermolytic toxins which are well documented staphylococcal virulence factors.
      SplA has a very narrow substrate specificity apparently imposed by the precise
      recognition of three amino acid residues positioned N-terminal to the hydrolysed
      peptide bond. To explain determinants of this extended specificity we resolve the
      crystal structure of SplA and define the consensus model of substrate binding.
      Furthermore we demonstrate that artificial N-terminal elongation of mature SplA
      mimicking a naturally present signal peptide abolishes enzymatic activity. The
      probable physiological role of the process is discussed. Of interest, even though
      precise N-terminal trimming is a common regulatory mechanism among S1 family
      enzymes, the crystal structure of SplA reveals novel significantly different
      mechanistic details.

PMID- 19175362
TI  - Safety, tolerability and pharmacokinetics of TAS-108, a novel anti-oestrogen, in
      healthy post-menopausal Japanese women: a phase I single oral dose study.
AB  - TAS-108 is a novel steroidal anti-oestrogen, expected to be useful for the
      treatment of breast cancer. The present study was conducted to investigate the
      safety, tolerability and pharmacokinetics of TAS-108 following the administration
      at a single oral dose of 40 mg to up to 120 mg in 12 post-menopausal women and
      the effect of food on the pharmacokinetics of the drug. All adverse events were
      mild and involved transient symptoms that resolved without therapeutic
      intervention. TAS-108 was readily absorbed and plasma levels of TAS-108 steadily
      declined, apparently in a multi-exponential manner. C(max) and AUC(0-12) were
      proportionally increased with increasing dose of TAS-108. The C(max) and AUC(0-t)
      of TAS-108 and its metabolite, deEt-TAS-108, were significantly increased to
      approximately 150% when TAS-108 was administered after a meal. Food did not
      affect the elimination half-life of TAS-108 or its metabolites. In this
      escalating dose-study of TAS-108, the drug was well tolerated by healthy post
      menopausal Japanese women. The pharmacokinetics of TAS-108 indicated dose
      proportionality, and its bioavailability was significantly increased by food
      intake.

PMID- 19175364
TI  - Curcumin protects PC12 cells from corticosterone-induced cytotoxicity: possible
      involvement of the ERK1/2 pathway.
AB  - Antiglucocorticoid therapy in depressed patients is effective, which indicates
      that glucocorticoids play a key role in the occurrence of depression. Our
      previous work demonstrated the efficacy of curcumin in treating depression in rat
      and mouse models. We characterized the protective effects of curcumin against
      corticosterone-induced cytotoxicity in PC12 cells and explored the mechanisms of
      these protective effects in association with the phosphorylation and expression
      of ERK1/2 in PC12 cells. MTT assay showed that curcumin significantly protected
      PC12 cells from corticosterone-induced cytotoxicity. Curcumin at concentrations
      from 10(-8) to 10(-6) M rescued PC12 cells from corticosterone-induced
      cytotoxicity. Cell viability was increased more than 20% with curcumin treatment.
      Western blot analysis showed that corticosterone increased ERK1/2 phosphorylation
      in PC12 cells and curcumin 10(-9) M to 10(-6) M significantly inhibited
      corticosterone-induced ERK1/2 phosphorylation in PC12 cells in a dose-dependent
      manner. These results suggest that curcumin is able to protect PC12 cells which
      may be associated with inhibition of ERK phosphorylation.

PMID- 19175365
TI  - Effects of rutin on lipid profile in hypercholesterolaemic rats.
AB  - Rutin (3, 3', 4', 5, 7-pentahydrohyflavone-3-rhamnoglucoside) is a flavonoid of
      the flavonol type. Rutin is found in many plants and is also an important dietary
      constituent of food and plant-based beverages. Rutin has several pharmacological
      properties including antioxidant and cardioprotective activities. Also, it was
      identified that rutin is the major low-density lipoprotein (LDL) antioxidant
      compound of mulberry in an in vitro study. The effects of rutin were tested by
      using it as a supplement in a high-cholesterol diet. Male rats were fed a high
      cholesterol diet (1 ml/100 g) for 4 weeks with rutin (10 or 100 mg/kg) or rutin
      100 mg/kg and lovastatin supplementation to study the hypocholesterolaemic
      effects of rutin on plasma lipid levels, hepatic enzyme activity, and liver
      tissue. Feeding the animals a high-cholesterol diet resulted in marked
      hypercholesterolaemia and increased the serum level of LDL cholesterol (LDL-C).
      Rutin (at 100 mg/kg) alone or in combination with lovastatin significantly
      reduced the levels of total cholesterol, and LDL-C and also markedly decreased
      liver enzymes and weight in animals with a high-cholesterol diet. Our findings
      show that 100 mg/kg of rutin alone or with lovastatin supplementation lowered
      liver weight and enzymes as well as plasma total cholesterol and LDL. The hepatic
      histopathological results reflect the correlation of rutin and lovastatin
      combination with both liver weight and the levels of plasma total cholesterol and
      LDL-C. These results indicate that rutin in combination with lovastatin has
      increased anti-hypercholesterolaemic effects in an animal model.

PMID- 19175366
TI  - Antigenotoxic, antioxidant and lymphocyte induction effects produced by
      pteropodine.
AB  - Pteropodine is a heterohimbine-type oxindole alkaloid specifically isolated from
      'Cat's claw' (Uncaria tomentosa), a plant that has shown cytostatic, anti
      inflammatory and antimutagenic properties and is used in traditional medicine to
      cure a number of diseases. In this report, we studied the ability of pteropodine
      to decrease the rate of sister-chromatid exchanges and micronucleated
      polychromatic erythrocytes in mice administered doxorubicin. We also determined
      its capacity to induce lymphocyte production in mice as well as its free radical
      scavenging potential by applying the DPPH assay. We found pteropodine (100-600
      mg/kg) to significantly decrease the frequency of sister-chromatid exchanges and
      micronucleated polychromatic erythrocytes in mice administered with 10 mg/kg of
      doxorubicin. Furthermore, we determined that pteropodine partially corrected bone
      marrow cytotoxicity induced by doxorubicin, as it showed an improvement in the
      rate of polychromatic erythrocytes. Besides, 600 mg/kg of pteropodine increased
      25.8% of the production of lymphocytes over the control value along a 96-hr
      assay, and it exhibited a strong capacity to trap the DPPH-free radical (98.26%
      with 250 microg/ml). Our results establish that pteropodine is an effective
      antimutagen in the model used, and suggest that pteropodine deserves further
      research in the area of cell protective potential and its mechanism of action.

PMID- 19175367
TI  - Evaluation of the effect of hydroalcoholic extract of Zingiber officinale
      rhizomes in rat collagen-induced arthritis.
AB  - Patients with chronic, painful diseases often seek alternative therapy. The
      purpose of this study was to investigate the potential of hydroalcoholic extract
      of Zingiber officinale rhizomes (Z. officinale extract) to ameliorate
      inflammatory process in rat collagen-induced arthritis. Our results show that Z.
      officinale extract in doses higher than 50 mg/kg/day intraperitoneally starting
      from the dose of booster immunization and for 26 days can ameliorate the clinical
      scores, disease incidence, joint temperature and swelling, and cartilage
      destruction, together with reduction of serum levels of interleukin (IL)-1beta,
      IL-2, IL-6, tumour necrosis factor-alpha, and anti-CII antibodies. Moreover, Z.
      officinale extract at the dose of 200 mg/kg/day was superior to 2 mg/kg/day of
      indomethacin at most of the measured parameters. These observations might make Z.
      officinale extract a good alternative to non-steroidal anti-inflammatory drugs
      for patients with rheumatoid arthritis.

PMID- 19175368
TI  - Cardiovascular biomarkers in groups of established smokers after a decade of
      smoking.
AB  - To investigate tools for evaluation of smoking-associated disease initiation and
      progression, we examined basic clinical parameters and biomarkers of
      cardiovascular disease risk, in a group of healthy volunteers with an average 10
      year smoking history. A small cross-sectional study of never-smokers, moderate
      smokers and smokers was performed. Caucasians were recruited to match pre-defined
      cigarette tar yields and cigarettes smoked per day. For haematological
      parameters, significant differences between never-smokers and all female smokers
      combined were seen for haemoglobin concentration, haematocrit, total leucocyte
      count, neutrophil count and lymphocyte count. For all male smokers combined, only
      total leucocyte count was statistically different. Analysis of exhaled CO and
      other smoke exposure biomarker (nicotine and its metabolites) data showed a
      statistically significant increase in all groups of smokers with a trend related
      to the number of cigarettes smoked per day. Thromboxane urinary metabolites 11
      dehydro-thromboxane B(2) and 2,3-dinor-thromboxane B(2) were statistically
      significantly elevated in smokers. Significant statistical differences between
      smokers with approximately 10 years of smoking history and non-smokers in white
      cells count, hemoglobin and thromboxane turnover were seen, although they did not
      reach levels associated with overt diseases. These data could provide insight
      into early biomarkers predictive of risk for coronary and vascular disease.

PMID- 19175369
TI  - A comparison of pharmacokinetics and pharmacodynamics of biphasic insulin aspart
      30, 50, 70 and pure insulin aspart: a randomized, quadruple crossover study.
AB  - The purpose of this study was to evaluate pharmacokinetic and pharmacodynamic
      profiles of pure insulin aspart and three different formulations of insulin
      aspart and protaminated insulin aspart: biphasic insulin aspart 30 (BIAsp30),
      biphasic insulin aspart 50 (BIAsp50) and biphasic insulin aspart 70 (BIAsp70).
      Nineteen type 1 diabetes patients received individually identical doses of the
      four different insulin aspart preparations on 4 separate days in this randomized
      crossover study. Having achieved overnight stable blood glucose control by
      intravenous infusions of human insulin, one of the trial insulins was injected
      subcutaneously and a standard meal was given in the morning. Plasma glucose and
      serum insulin aspart were recorded the following 12 hr. During the first 4 hr
      after injection with the trial insulin, the area under the curve for levels of
      insulin aspart (AUC(ins)) was significantly higher during insulin aspart
      treatment as compared to the other three insulin treatments, followed by BIAsp70,
      BIAsp50 and BIAsp30 (P < 0.05). Over the last 4 hr, the AUC(ins) for BIAsp30 was
      significantly higher as compared to the other insulin preparations (P < 0.05). By
      contrast, during the initial 4 hr, the area under the curve for levels of glucose
      (AUC(glu)) was highest after injection with BIAsp30 compared to the other three
      treatments (P < 0.05), while during the last 4 hr the highest AUC(glu) was seen
      following insulin aspart (P < 0.05). We conclude that when insulin aspart is pure
      or formulated with protamine in three different ratios, the pharmacokinetic
      profiles are readily distinguishable. These differences in pharmacokinetics are
      reflected in the pharmacodynamic profiles.

PMID- 19175370
TI  - A refined surgical treatment modality for bromhidrosis: double w incision
      approach with tumescent technique.
AB  - BACKGROUND: Axillary bromhidrosis has a strong negative effect on one's social
      life. A high success rate and few complications are criteria for an ideal
      treatment method. OBJECTIVE: To evaluate a new surgical treatment modality for
      bromhidrosis: Double W incision with full-exposure excision under tumescent
      anesthesia. MATERIALS & METHODS: Twenty patients with bromhidrosis were treated.
      Patients were placed in a supine position with their treated arms abducted to 110
      degrees . After injection of 60 mL of tumescent solution into each axilla, two
      small W incisions were made at the superior and inferior axillary poles of the
      hair-bearing area. The whole hair-bearing skin was undermined at the level of the
      superficial fat to obtain adequate skin eversion. The flaps were everted to offer
      full exposure of the apocrine glands, and meticulous excision of each gland was
      performed. Finally, the incisions were re-approximated, and bulky compressive
      dressings were applied to the area for 72 hours. RESULTS: Of the 40 axillae (20
      patients), 32 (80.0%) showed excellent results, and eight (20.0%) had good
      results. Malodor was significantly decreased. There were no serious
      complications. CONCLUSION: This technique can produce excellent results with a
      lower complication rate than most other surgical modalities and can be performed
      without costly equipment.

PMID- 19175371
TI  - Prevention of thyroidectomy scar using a new 1,550-nm fractional erbium-glass
      laser.
AB  - BACKGROUND: Surgical scars are a common cosmetic problem that occurs in various
      surgical fields including dermatology. Diverse trials have been made to prevent
      this annoying scar formation. Recently, 585- and 595-nm pulsed dye laser
      irradiation presented satisfactory cosmetic outcome for the treatment of surgical
      scars. Other fractionated lasers or light devices were also applied for scar
      treatment. OBJECTIVE: To determine the effectiveness and safety of a newly
      developed 1,550-nm fractional erbium-glass laser in the prevention of scar
      formation after total thyroidectomy. MATERIALS AND METHODS: Twenty-seven ethnic
      South Korean patients with linear surgical suture lines after total thyroidectomy
      operation were treated with a 1,550-nm fractional erbium-glass laser. The same
      surgeon performed all of the operations using the same surgical techniques. Each
      patient was treated four times at 1-month intervals using the same parameters (5-
      x 10-mm spot size, 10 mJ, 1,500 spot/cm(2), static mode). Initiation of the first
      irradiation was made approximately 2 to 3 weeks after the thyroidectomy. The scar
      prevention effects were evaluated each month for 6 months after thyroidectomy.
      Two kinds of assessment methods were applied in this evaluation. First, the
      Vancouver Scar Scale (VSS) was used. Second, three independent physicians gave a
      global assessment valuation to the final cosmetic results: poor (1), fair (2),
      good (3), or excellent (4). These results were compared with the surgical scars
      of a control group (patients who denied laser treatments and had no other
      treatments during the 6 months after total thyroidectomy by the same surgeon).
      RESULTS: The average VSS score was lower in the laser treatment group. The global
      assessment also presented better cosmetic outcomes in the treatment group than in
      the controls. CONCLUSION: A new 1,550-nm fractional erbium-glass laser may
      efficiently repress the formation and hypertrophy of thyroidectomy scars on the
      neck, and it can be safely applied in relatively dark Asian skin without
      noticeable adverse effects.

PMID- 19175372
TI  - Comparison of a pulsed dye laser and a combined 585/1,064-nm laser in the
      treatment of acne vulgaris.
AB  - BACKGROUND: The effect of combined 585/1,064-nm (sequential dual-wavelength
      pulsed dye laser (PDL) and neodymium-doped yttrium aluminium garnet) laser
      therapy for acne vulgaris has not been evaluated. OBJECTIVES: To compare the
      efficacy and safety of PDL and of combined 585/1,064-nm laser treatment for mild
      to moderate facial acne. METHODS: A 12-week, randomized, prospective, split-face,
      double-blind study was performed. Sixteen participants with mild to moderate acne
      were treated with a single pass of a combined 585/1,064-nm laser on half of the
      face and PDL on the other half during each treatment session. Patients underwent
      three treatment sessions at 2-week intervals and were followed up at 8 and 12
      weeks after treatment commencement. RESULTS: At the final visit, inflammatory
      acne lesions were reduced by 86% on the PDL sides and by 89% on the 585/1,064-nm
      laser sides. Noninflammatory acne lesions showed corresponding reductions of 69%
      and 64%, respectively. A significant difference between the two treatments was
      observed for noninflammatory acne lesions at the eighth week. Histopathologic
      examinations showed that both treatments decreased inflammation and interleukin-8
      expression and increased transforming growth factor beta expression. CONCLUSIONS:
      PDL and combined 585/1,064 nm laser were safe and effective for the treatment of
      inflammatory and noninflammatory acne lesions.

PMID- 19175373
TI  - Fixed-dose single tablet antidiabetic combinations.
AB  - Combinations of two or more oral agents with different mechanisms of action are
      often used for the management of hyperglycaemia in type 2 diabetes. While these
      combinations have customarily been taken as separate tablets, several fixed-dose
      single tablet combinations are now available. These are based on bioequivalence
      with the separate tablets, giving similar efficacy to the separate tablets and
      necessitating the same cautions and contraindications that apply to each active
      component. Fixed-dose combinations can offer convenience, reduce the pill burden
      and simplify administration regimens for the patient. They increase patient
      adherence compared with equivalent combinations of separate tablets, and this is
      associated with some improvements in glycaemic control. Presently available
      antidiabetic fixed-dose combinations include metformin combined with a
      sulphonylurea, thiazolidinedione, dipeptidylpeptidase-4 inhibitor or meglitinide
      as well as thiazolidinedione-sulphonylurea combinations, each at a range of
      dosage strengths to facilitate titration. Anticipated future expansion of
      multiple drug regimens for diabetes management is likely to increase the use of
      fixed-dose single tablet combinations.

PMID- 19175374
TI  - A low-GI diet is associated with a short-term improvement of glycaemic control in
      Asian patients with type 2 diabetes.
AB  - AIMS: The aim of this study is to compare the efficacy of low glycaemic index
      (GI) vs. conventional carbohydrate exchange (CCE) dietary advice on glycaemic
      control and metabolic parameters in patients with type 2 diabetes. METHODS: A
      total of 104 patients with type 2 diabetes were randomly assigned to either a low
      GI (GI) or CCE dietary advice over a 12-week period. The primary end-point was
      glycaemic control as assessed by glycated haemoglobin A1c (HbA1c), fructosamine
      level and plasma glucose. The secondary end-points were anthropometric
      measurements and metabolic parameters that include blood pressure, lipid profile
      and insulin levels. The oral antidiabetic medications remained unchanged
      throughout the duration of the study. RESULTS: A low-GI diet was associated with
      significant changes in the fructosamine level (DeltaGI = -0.20 +/- 0.03; DeltaCCE
      = -0.08 +/- 0.03 mmol/l, p < 0.01) and waist circumference (DeltaGI group = -1.88
      +/- 0.30 cm; DeltaCCE group: -0.36 +/- 0.4 cm, p < 0.05) at week 4. At week 12,
      the changes in fasting glucose (DeltaGI = -0.03 +/- 0.3; DeltaCCE = 0.7 +/- 0.3
      mmol/l; p < 0.05) and waist circumference (DeltaGI = -2.35 +/- 0.47 cm; DeltaCCE
      group = -0.66 +/- 0.46 cm; p < 0.05) in the GI group was significantly lower than
      the CCE group. With the low-GI diet, the changes in postprandial glycaemia at
      time 0, 60, 150 and 180 min after consuming the standard test meal was lower than
      with the CCE diet (p < 0.05). No significant differences were found between the
      groups for the remaining parameters that were measured. CONCLUSIONS: Use of a low
      GI diet resulted in significant changes of serum fructosamine level, plasma
      glucose and waist circumference in Asian patients with type 2 diabetes over a 12
      week period compared with those following a CCE diet. The effect on HbA1c and
      other metabolic parameters was not significantly different between the two study
      groups but the improvement within the GI group was more pronounced and of
      clinical benefit.

PMID- 19175375
TI  - Insulin therapy in type 2 diabetes: what is the evidence?
AB  - AIM: To systematically review the literature regarding insulin use in patients
      with type 2 diabetes mellitus METHODS: A Medline and Embase search was performed
      to identify randomized controlled trials (RCT) published in English between 1
      January 2000 and 1 April 2008, involving insulin therapy in adults with type 2
      diabetes mellitus. The RCTs must comprise at least glycaemic control
      (glycosylated haemoglobin (HbA1c), postprandial plasma glucose and /or fasting
      blood glucose (FBG)) and hypoglycaemic events as outcome measurements. RESULTS:
      The Pubmed search resulted in 943 hits; the Embase search gave 692 hits. A total
      of 116 RCTs were selected by title or abstract. Eventually 78 trials met the
      inclusion criteria. The studies were very diverse and of different quality. They
      comprised all possible insulin regimens with and without combination with oral
      medication. Continuing metformin and/or sulphonylurea after start of therapy with
      basal long-acting insulin results in better glycaemic control with less insulin
      requirements, less weight gain and less hypoglycaemic events. Long-acting insulin
      analogues in combination with oral medication are associated with similar
      glycaemic control but fewer hypoglycaemic episodes compared with NPH insulin.
      Most of the trials demonstrated better glycaemic control with premix insulin
      therapy than with a long-acting insulin once daily, but premix insulin causes
      more hypoglycaemic episodes. Analogue premix provides similar HbA1c, but lower
      postprandial glucose levels compared with human premix, without increase in
      hypoglycaemic events or weight gain. Drawing conclusions from the limited number
      of studies concerning basal-bolus regimen seems not possible. Some studies showed
      that rapid-acting insulin analogues frequently result in a better HbA1c or
      postprandial glucose without increase of hypoglycaemia than regular human
      insulin. CONCLUSION: A once-daily basal insulin regimen added to oral medication
      is an ideal starting point. All next steps, from one to two or even more
      injections per day should be taken very carefully and in thorough deliberation
      with the patient, who has to comply with such a regimen for many years.

PMID- 19175376
TI  - DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose
      tissue.
AB  - CONTEXT: Dipeptidyl peptidase IV (DPP-IV) inactivates the incretin hormone
      glucagon-like peptide. It can also affect the orexigenic hormone neuropeptide Y
      (NPY(1-36)) which is truncated by DPP-IV to NPY(3-36), as a consequence NPY's
      affinity changes from receptor Y1, which mediates the antilipolytic function of
      NPY, to other NPY receptors. Little is known whether DPP-IV inhibitors for the
      treatment of type 2 diabetic (T2DM) patients could influence these pathways.
      AIMS: To investigate the in vitro effects of NPY with DPP-IV inhibition in
      isolated abdominal subcutaneous (AbdSc) adipocytes on fat metabolism, and
      assessment of NPY receptor and DPP-IV expression in adipose tissue (AT). METHODS:
      Ex vivo human AT was taken from women undergoing elective surgery (body mass
      index: 27.5 (mean +/- s.d.) +/- 5 kg/m2, age: 43.7 +/- 10 years, n = 36).
      Isolated AbdSc adipocytes were treated with human recombinant (rh)NPY (1-100 nM)
      with and without DPP-IV inhibitor (1 M); glycerol release and tissue distribution
      of DPP-IV, Y1 and Y5 messenger RNA (mRNA) were measured and compared between lean
      and obese subjects. RESULTS AND CONCLUSION: rhNPY reduced glycerol release, an
      effect that was further enhanced by co-incubation with a DPP-IV inhibitor
      [control: 224 (mean +/- s.e.) +/- 37 micromol/l; NPY, 100 nM: 161 +/- 27
      micromol/l**; NPY 100 nM/DPP-IV inhibitor, 1 M: 127 +/- 14 micromol/l**; **p <
      0.01, n = 14]. DPP-IV was expressed in AbdSc AT and omental AT with relative DPP
      IV mRNA expression lower in AbdSc AT taken from obese [77 +/- 6 signal units
      (SU)] vs. lean subjects (186 +/- 29 SU*, n = 10). Y1 was predominantly expressed
      in fat and present in all fat depots but higher in obese subjects, particularly
      the AbdSc AT-depot (obese: 1944 +/- 111 SU vs. lean: 711 +/- 112 SU**, n = 10).
      NPY appears to be regulated by AT-derived DPP-IV. DPP-IV inhibitors augment the
      antilipolytic effect of NPY in AT. Further studies are required to show whether
      this explains the lack of weight loss in T2DM patients treated with DPP-IV
      inhibitors.

PMID- 19175377
TI  - Effects of cevoglitazar, a dual PPARalpha/gamma agonist, on ectopic fat
      deposition in fatty Zucker rats.
AB  - AIM: By acting as both insulin sensitizers and lipid-lowering agents, dual-acting
      peroxisome proliferator-activated receptors alpha/gamma (PPARalpha/gamma)
      agonists may be used to improve glucose tolerance in type 2 diabetic patients
      without inducing adiposity and body weight gain. Here, in an animal model of
      obesity and insulin resistance, the metabolic response to cevoglitazar, a dual
      PPARalpha/gamma, was characterized using a combination of in vivo and ex vivo
      magnetic resonance methodologies and compared to treatment effects of
      fenofibrate, a PPARalpha agonist, and pioglitazone, a PPARgamma agonist. METHODS:
      Four groups of fatty Zucker rats: (i) Vehicle; (ii) fenofibrate 150 mg/kg; (iii)
      pioglitazone 30 mg/kg; and (iv) cevoglitazar 5 mg/kg were investigated before and
      after treatment. Animals were fed a fat-enriched (54% kcal fat) diet for 6 weeks,
      2 weeks high of fat-exposure alone followed by a 4-week dosing period. RESULTS
      AND CONCLUSIONS: Cevoglitazar was as effective as pioglitazone at improving
      glucose tolerance. However, unlike pioglitazone, both fenofibrate and
      cevoglitazar reduced BW gain and adiposity, independent of food intake. All three
      treatment regimens normalized intramyocellular lipids. Metabolic profiling showed
      that in the muscle cevoglitazar improves the lipid profile via both PPARalpha-
      and PPARgamma-mediated mechanisms. Pioglitazone reduced hepatic lipid
      accumulation, while cevoglitazar and fenofibrate reduced hepatic lipid
      concentration below baseline levels (p < 0.05). Metabolic profiling showed that
      in the liver, cevoglitazar functions largely through PPARalpha agonism resulting
      in increased beta-oxidation. Cevoglitazar only induced small changes to the lipid
      composition of visceral fat. In subcutaneous fat, however, cevoglitazar induced
      changes similar to those observed with fenofibrate suggesting export of fatty
      acids from this depot.

PMID- 19175378
TI  - Reverse cholesterol transport in type 2 diabetes mellitus.
AB  - High-density lipoprotein (HDL) plays an important protective role against
      atherosclerosis, and the anti-atherogenic properties of HDL include the promotion
      of cellular cholesterol efflux and reverse cholesterol transport (RCT), as well
      as antioxidant, anti-inflammatory and anticoagulant effects. RCT is a complex
      pathway, which transports cholesterol from peripheral cells and tissues to the
      liver for its metabolism and biliary excretion. The major steps in the RCT
      pathway include the efflux of free cholesterol mediated by cholesterol
      transporters from cells to the main extracellular acceptor HDL, the conversion of
      free cholesterol to cholesteryl esters and the subsequent removal of cholesteryl
      ester in HDL by the liver. The efficiency of RCT is influenced by the
      mobilization of cellular lipids for efflux and the intravascular remodelling and
      kinetics of HDL metabolism. Despite the increased cardiovascular risk in people
      with type 2 diabetes, current knowledge on RCT in diabetes is limited. In this
      article, abnormalities in RCT in type 2 diabetes mellitus and therapeutic
      strategies targeting HDL and RCT will be reviewed.

PMID- 19175379
TI  - Unilateral RLS with predominantly ipsilateral PLMS and variable response to
      dopaminergic drugs: a variant of idiopathic RLS?
AB  - BACKGROUND: Restless legs syndrome (RLS) is characterized by sensorimotor
      symptoms that usually are localized in both legs, but may present considerable
      asymmetry. Patients with strictly and persisting unilateral manifestations have
      not yet been reported. METHODS: We describe the clinical and electrophysiological
      characteristics of three RLS patients with unilateral symptoms. RESULTS: All
      essential RLS criteria were fulfilled in each patient. Neuroimaging and
      electrophysiological studies did not reveal structural lesions. All patients
      showed a predominance of periodic limb movements in sleep (PLMS) ipsilaterally to
      the RLS symptoms. Treatment response to dopaminergic drugs was favourable only in
      one patient. CONTROLS: Our observations suggest the existence of unilateral RLS
      with predominantly ipsilateral PLMS as a (so-far unrecognized) variant of RLS.

PMID- 19175380
TI  - One-year follow up of patients with chronic tinnitus treated with left
      temporoparietal rTMS.
AB  - BACKGROUND AND PURPOSE: Although there are a number of positive reports on the
      therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) for
      treatment of tinnitus, there are few details about the duration of treatment
      effects or the relative efficiency of different rTMS protocols. METHODS: Sixty
      six patients with chronic tinnitus were divided into four groups, receiving sham
      rTMS, 1, 10 and 25 Hz rTMS applied each day for 10 days over left temporoparietal
      cortex. They were followed up at 4 months and 1 year using the tinnitus
      questionnaire [Tinnitus Handicap Inventory(THI)] and self ratings of annoyance as
      well as measures of residual inhibition. RESULTS: A two factor anova revealed a
      significant 'rTMS' x 'time' interaction indicating that real and sham rTMS had
      different effects on the THI scale and annoyance of tinnitus (P = 0.026 and 0.046
      respectively). After 1 year, the tinnitus was absent in one or both ears of 10
      patients who had received real rTMS: one of these was in the 1 Hz group, four
      patients were in the 10 Hz group and five patients were in the 25 Hz group.
      CONCLUSION: Some patients show a lasting benefit at 1 year after 10 days of rTMS
      treatment. It appears that treatment at 10 or 25 Hz may be more beneficial than
      at 1 Hz, although more work is necessary to validate this conclusion.

PMID- 19175381
TI  - Cerebral autoregulation in patients with obstructive sleep apnea syndrome during
      wakefulness.
AB  - BACKGROUND AND PURPOSE: Obstructive sleep apnea syndrome (OSAS) is an independent
      risk factor for stroke. Impairment of cerebral autoregulation may play a
      potential role in the pre-disposition to stroke of OSAS patients. In this study,
      we aimed to assess dynamic cerebral autoregulation (DCA) during wakefulness in
      OSAS patients and a group of matched controls. METHODS: Patients and controls
      were examined in the morning after an overnight complete polysomnography. Mean
      cerebral blood flow velocity (CBFV) in the middle cerebral artery and mean
      arterial blood pressure (ABP) were continuously recorded using transcranial
      Doppler and Finapres. DCA was assessed using the Mx autoregulatory index. Mx is a
      moving correlation coefficient between mean CBFV and mean ABP. More positive
      value of Mx indicates worse autoregulation. RESULTS: Eleven OSAS patients (mean
      age +/- SD; 52.6 +/- 7.9) and 9 controls (mean age +/- SD; 49.1 +/- 5.3) were
      enrolled. The mean apnea-hypopnea index (AHI) in the OSAS group was of 22.7 +/-
      11.6. No significant difference was found between the two groups as for age, body
      mass index, mean ABP and endtidal CO(2) pressure. Cerebral autoregulation was
      impaired in OSAS patients compared with controls (Mx index: 0.414 +/- 0.138 vs.
      0.233 +/- 0.100; P = 0.009). The severity of autoregulation impairment correlated
      to the severity of the sleep respiratory disturbance measured by the AHI (P =
      0.003). CONCLUSION: Cerebral autoregulation is impaired in patients with OSAS
      during wakefulness. Impairment of cerebral autoregulation is correlated with the
      severity of OSAS.

PMID- 19175382
TI  - Multiple sclerosis patients with anti-lipid oligoclonal IgM show early favourable
      response to immunomodulatory treatment.
AB  - BACKGROUND AND PURPOSE: Interferon beta and Glatiramer acetate are safe
      immunomodulatory treatments (IT) for multiple sclerosis (MS), but not always
      effective. New drugs are available, although they show more side-effects and
      unknown long-term safety profile. Anti-lipid oligoclonal IgM bands (OCMB)
      distinguish MS patients with early aggressive course. We prospectively studied if
      IT are effective in these patients or if they are candidates for more aggressive
      drugs as first therapeutic option. METHODS: Seventy-five clinically isolated
      syndrome patients were studied. OCMB and conversion to MS were assessed. Patients
      suffering at least two demyelinating events within 3 years were considered
      eligible to start IT. RESULTS: Eighteen patients showed OCMB (M+) and 57 lacked
      them (M-). All M+ patients and only 25 M- patients were treated. The other 32 M-
      patients suffered less MS attacks than those required to initiate treatment. IT
      similarly reduced relapse rate in both treated groups (P < 0.0001) and reduced
      Expanded Disability Status Scale (EDSS) progression in M+ patients, whose EDSS
      score had significantly increased before treatment. EDSS did not change in M-
      patients during follow-up, regardless if they were treated or not. CONCLUSIONS:
      Oligoclonal IgM bands identify MS patients who are candidates for early
      immunomodulatory treatment as IT improves their initial aggressive disease
      course.

PMID- 19175383
TI  - Lack of association of hormone receptor polymorphisms with migraine.
AB  - BACKGROUND AND PURPOSE: Previous studies concerning the role of hormone receptor
      genetic variants in migraine have provided conflicting results. The aim of this
      study was to investigate the role of common polymorphisms in the estrogen
      receptor gene (ESR1) and the progesterone receptor gene (PGR) in the risk for
      migraine in a Spanish population. METHODS: In a case-control study, including 210
      Caucasoid migraine patients and 210 controls, we examined association between
      three single nucleotide polymorphisms in the coding region of ESR1, rs2077642,
      rs1801132, and rs2228480, and an Alu insertion in PGR, and migraine, migraine
      without aura or migraine with aura. Genotypic, allelic and reconstructed
      haplotype distributions were compared. RESULTS: We found no significant
      differences between cases and controls in the distribution of genotypes or
      alleles for either polymorphism. No haplotype was over-represented in patients.
      CONCLUSIONS: Our study does not support a major contribution of ESR1 and PGR to
      the pathogenesis of migraine.

PMID- 19175384
TI  - Cladribine impedes in vitro migration of mononuclear cells: a possible
      implication for treating multiple sclerosis.
AB  - BACKGROUND: Damage of the blood-brain barrier and the migration of
      immunocompetent cells into the CNS represent key events in the immunopathogenesis
      of multiple sclerosis (MS). Cladribine is an immunosuppressive drug currently
      investigated in a phase-III clinical trial for relapsing-remitting MS. However,
      its precise mode of action remains elusive so far. METHODS: Peripheral blood
      mononuclear cells (PBMCs) were isolated from five patients with MS and five
      healthy donors. PBMCs were treated with cladribine in vitro. The migratory
      capacity was studied in an in vitro Boyden chamber assay; cells and their rate of
      migration were analyzed by light microscopy and flow cytometry. RESULTS:
      Cladribine decreased the migratory capacity of CD14(+) monocytes, as well as of
      CD4(+) and CD8(+) T lymphocytes. T lymphocytes were affected more than monocytes.
      There was no difference in this effect when comparing mononuclear cells from MS
      patients with cells from healthy controls. CONCLUSIONS: Cladribine might achieve,
      at least in part, its clinical and paraclinical efficacy by inhibiting the
      migration of inflammatory cells into and within the CNS.

PMID- 19175385
TI  - Assessment and surgical outcomes for mild type I and severe type II cortical
      dysplasia: a critical review and the UCLA experience.
AB  - Recent findings on the clinical, electroencephalography (EEG), neuroimaging, and
      surgical outcomes are reviewed comparing patients with Palmini type I (mild) and
      type II (severe) cortical dysplasia. Resources include peer-reviewed studies on
      surgically treated patients and a subanalysis of the 2004 International League
      Against Epilepsy (ILAE) Survey of Pediatric Epilepsy Surgery. These sources were
      supplemented with data from University of California, Los Angeles (UCLA).
      Cortical dysplasia is the most frequent histopathologic substrate in children,
      and the second most common etiology in adult epilepsy surgery patients. Cortical
      dysplasia patients present with seizures at an earlier age than other surgically
      treated etiologies, and 33-50% have nonlocalized scalp EEG and normal magnetic
      resonance imaging (MRI) scans. 2-((18)F)Fluoro-2-deoxy-D-glucose positron
      emission tomography (FDG-PET) is positive in 75-90% of cases. After complete
      resection, 80% of patients are seizure free compared with 20% with incomplete
      resections. Compared with type I, patients with type II cortical dysplasia
      present at younger ages, have higher seizure frequencies, and are extratemporal.
      Type I dysplasia is found more often in adult patients in the temporal lobe and
      is often MRI negative. These findings identify characteristics of patients with
      mild and severe cortical dysplasia that define surgically treated epilepsy
      syndromes. The authors discuss future challenges to identifying and treating
      medically refractory epilepsy patients with cortical dysplasia.

PMID- 19175386
TI  - The spectrum of benign myoclonus of early infancy: Clinical and neurophysiologic
      features in 102 patients.
AB  - PURPOSE: To redefine benign myoclonus of early infancy (BMEI) through analysis of
      clinical and neurophysiologic features in 102 patients with the aim to widen the
      spectrum of the syndrome, including a number of different clinical expressions of
      transient nonepileptic paroxysmal movements occurring in normal infants. METHODS:
      We recruited patients from one center in Argentina and two in Italy, including
      infants with normal neurologic and psychomotor development presenting with brief
      paroxysmal abnormal movements. Children with motor phenomena occurring only
      during sleep were excluded. Patients with abnormal interictal or ictal
      electroencephalography (EEG) findings were also excluded. The follow-up ranged
      from 2-40 years. RESULTS: One hundred and two infants (60 male) met the inclusion
      criteria. Age at onset ranged from 1-12 months, with a median age of 6.2 months.
      The following nonepileptic paroxysmal motor phenomena were recognized: (1)
      myoclonus, (2) spasms and brief tonic contractions, (3) shuddering, (4) atonia or
      negative myoclonus, (5) more than one type of motor phenomenon. In the majority
      of cases the episodes occurred only while awake and repeated several times a day.
      In 45 (44.1%) of the 102 cases contractions appeared in clusters. CONCLUSIONS:
      Based on the analysis of clinical and EMG features in this large series of
      infants, we postulate that the spectrum of the syndrome is wider than initially
      suspected, and that the different transient motor manifestations and their
      correlation with different EMG patterns will allow recognition of this definitely
      benign condition comprising a variety of episodic motor phenomena in normal
      babies.

PMID- 19175387
TI  - Duration of refractory status epilepticus and outcome: loss of prognostic utility
      after several hours.
AB  - PURPOSE: Outcome for patients with status epilepticus (SE) depends strongly on
      etiology. Duration of SE is also predictive, at least in the first 2 h, but
      beyond this it is unclear that duration of SE influences outcome significantly.
      We sought to determine the influence of duration of SE on outcome in patients
      with prolonged SE, and to compare this influence with that of other factors.
      METHODS: We reviewed the clinical course and outcome of 119 patients with SE,
      diagnosed by both clinical manifestations and electroencephalography (EEG)
      evidence. Using univariate and multivariate analyses, we sought predictors of
      outcome (survival vs. death or vegetative state) among age, etiology (epilepsy,
      anoxia or severe hypoxia, or other), presence of earlier epilepsy, multiple
      medical problems, presentation in coma, and type of SE (focal or generalized).
      RESULTS: Median duration of SE was 48 h. Survival was greater with a shorter
      duration, especially when <10 h (69% vs. 31% for longer duration; p < 0.05).
      Epilepsy as the etiology, and an earlier diagnosis of epilepsy offered a
      favorable prognosis (p < 0.01), but only the former on multivariate analysis.
      Coma and SE caused by anoxia/hypoxia were unfavorable factors. Once corrected for
      etiology, presentation in coma, and type of SE (focal or generalized), duration
      of SE did not have a significant effect on outcome. Overall mortality was high,
      65%, but 10 patients survived SE lasting over 3.5 days. CONCLUSIONS: A duration
      of <10 h was associated with better outcome in SE, but this was not significant
      once etiology, presentation in coma, and type of SE were accounted for. Etiology
      of SE is still the primary determinant of outcome. Unless it follows anoxia,
      prolonged SE should not be considered a hopeless condition.

PMID- 19175388
TI  - Epilepsy surgery in the first 3 years of life: a Canadian survey.
AB  - OBJECTIVE: To determine the clinical characteristics, surgical challenges, and
      outcome in children younger than 3 years of age undergoing epilepsy surgery in
      Canada. METHODS: Retrospective data on patients younger than age 3 years who
      underwent epilepsy surgery at multiple centers across Canada from January 1987 to
      September 2005 were collected and analyzed. RESULTS: There were 116 patients from
      eight centers. Seizure onset was in the first year of life in 82%, and mean age
      at first surgery was 15.8 months (1-35 months). Second surgeries were done in 27
      patients, and a third surgery in 6. Etiologies were malformations of cortical
      development (57), tumor (22), Sturge-Weber syndrome (19), infarct (8), and other
      (10). Surgeries comprised 40 hemispheric operations, 33 cortical resections, 35
      lesionectomies, 7 temporal lobectomies, and one callosotomy. There was one
      surgical mortality. The most common surgical complications (151 operations in 116
      patients) were infection (17) and aseptic meningitis in 13. Of 107 patients with
      seizure outcome assessed more than one year postoperatively, 72 (67.3%) were
      seizure free (Engel I), 15(14%) had >90% improvement (Engel II), 12 had >50%
      improvement (Engel III), and 8 did not benefit from surgery (Engel IV).
      Development improved in 55.3% after surgery. CONCLUSION: Epilepsy surgery in
      children younger than 3 years of age is relatively safe and is effective in
      controlling seizures. Very young age is not a contraindication to surgery in
      children with refractory epilepsy, and early surgery may impact development
      positively.

PMID- 19175389
TI  - Sleep-related hypermotor seizures in aspartylglucosaminuria: a case report.
AB  - From the age of 24 years a young man with a definitive diagnosis of
      aspartylglucosaminuria (AGU) presented short-lasting sleep-related paroxysmal
      events characterized by sudden awakening with a frightened look,
      hyperventilation, and complex bilateral motor activity. Nocturnal video
      polysomnography recorded several events consistent with a diagnosis of hypermotor
      epileptic seizures. This pattern of sleep-related epileptic seizures has been
      reported in rare familial cases, more often in cryptogenic and symptomatic
      patients in the spectrum of nocturnal frontal lobe epilepsy. Epilepsy and sleep
      related nonepileptic problems are common in patients with AGU, but no case of
      hyperkinetic nocturnal frontal lobe seizures has been reported to date.
      Differential diagnosis of abnormal paroxysmal motor events in sleep is frequently
      a challenge for the clinician: Video-polysomnographic recordings might serve to
      identify the possible epileptic origin of some of the excessive motor activities
      during sleep referred in patients with AGU.

PMID- 19175390
TI  - Decreased cerebrospinal fluid hypocretin-1 (orexin A) in patients after
      repetitive generalized tonic-clonic seizures.
AB  - The effects of seizures on the hypocretin/orexin system have not yet been
      investigated in epileptic patients. The present study aimed to assay hypocretin-1
      in the cerebrospinal fluid (CSF) of patients after generalized tonic-clonic (GTC)
      seizures. Study groups consisted of 21 patients after GTC seizures and 19
      controls. Diagnostic lumbar puncture was performed in control and epileptic
      patients within 48 h after the GTC seizures. Hypocretin-1 levels were measured in
      unextracted CSF samples, using a standardized commercial radioimmunoassay. There
      was a significant overall difference in median CSF hypocretin-1 concentrations
      between controls and patients with GTC patients (p < 0.001). The lowest
      concentrations were noted in a subgroup of patients with repetitive GTC seizures
      (RS) compared to those with a single GTC seizure (SS) (p > 0.05) or controls (p <
      0.001). The current results suggest that the hypocretin-1 system deficiency
      contributes to the complex pathophysiology of repetitive GTC seizures and status
      epilepticus (SE) and could be associated with typical somnolence after seizure
      attacks.

PMID- 19175392
TI  - Surgery for pharmacoresistant epilepsy in the developing world: A pilot study.
AB  - Epilepsy prevalence in the developing world is many fold that found in developed
      countries. For individuals whose conditions failed to respond to pharmacotherapy,
      surgery is the only opportunity for cure. In Uganda, we developed a center for
      treatment of intractable temporal lobe epilepsy (iTLE) that functions within the
      technologic and expertise constraints of a severely low resource area. Our model
      relies on partnership with epilepsy professionals and training of local staff.
      Patients were prescreened at regional clinics for iTLE. Individuals meeting
      inclusion criteria were referred to the treating Ugandan hospital (CURE
      Children's' Hospital of Uganda, CCHU) for video-EEG (electroencephalography),
      computed tomography (CT) imaging, and neuropsychological evaluation. Data were
      transferred to epilepsy experts for analysis and treatment recommendations. Ten
      patients were diagnosed with iTLE and surgically treated at CCHU. Six (60%) were
      seizure free, and there was no neurologic morbidity or mortality. Our model for
      surgical treatment of pharmacoresistant TLE has functioned successfully in a true
      developing world low resource setting.

PMID- 19175391
TI  - Blood-brain barrier damage and brain penetration of antiepileptic drugs: role of
      serum proteins and brain edema.
AB  - PURPOSE: Increased blood-brain barrier (BBB) permeability is radiologically
      detectable in regions affected by drug-resistant epileptogenic lesions. Brain
      penetration of antiepileptic drugs (AEDs) may be affected by BBB damage. We
      studied the effects of BBB damage on brain distribution of hydrophilic [deoxy
      glucose (DOG) and sucrose] and lipophilic (phenytoin and diazepam) molecules. We
      tested the hypothesis that lipophilic and hydrophilic drug distribution is
      differentially affected by BBB damage. METHODS: In vivo BBB disruption (BBBD) was
      performed in rats by intracarotid injection of hyperosmotic mannitol. Drugs (H3
      sucrose, 3H-deoxy-glucose, 14C-phenytoin, and C14-diazepam) or unlabeled
      phenytoin was measured and correlated to brain water content and protein
      extravasation. In vitro hippocampal slices were exposed to different
      osmolarities; drug penetration and water content were assessed by analytic and
      densitometric methods, respectively. RESULTS: BBBD resulted in extravasation of
      serum protein and radiolabeled drugs, but was associated with no significant
      change in brain water. Large shifts in water content in brain slices in vitro
      caused a small effect on drug penetration. In both cases, total drug permeability
      increase was greater for lipophilic than hydrophilic compounds. BBBD reduced the
      amount of free phenytoin in the brain. DISCUSSION: After BBBD, drug binding to
      protein is the main controller of total brain drug accumulation. Osmotic BBBD
      increased serum protein extravasation and reduced free phenytoin brain levels.
      These results underlie the importance of brain environment and BBB integrity in
      determining drug distribution to the brain. If confirmed in drug-resistant
      models, these mechanisms could contribute to drug brain distribution in
      refractory epilepsies.

PMID- 19175393
TI  - Intrahippocampal infusion of botulinum neurotoxin E (BoNT/E) reduces spontaneous
      recurrent seizures in a mouse model of mesial temporal lobe epilepsy.
AB  - Mesial temporal lobe epilepsy (MTLE) is one of the most common forms of human
      epilepsy, and it is often resistant to conventional antiepileptic drug (AED)
      therapy. Here we tested whether a single intrahippocampal administration of the
      synaptic blocker botulinum neurotoxin E (BoNT/E) is effective in reducing
      spontaneous recurrent seizures (SRS) in a mouse model of MTLE. Unilateral
      intrahippocampal injection of kainic acid (KA) in mice was used as a model of
      MTLE. Electroencephalography (EEG) recordings of SRS were performed during the
      chronic phase of epilepsy, before and after administration of either BoNT/E or
      vehicle. Frequency of SRS was significantly decreased for at least 5 days
      following BoNT/E, but not vehicle, infusion. Our findings demonstrate that BoNT/E
      can effectively reduce seizure incidence in a mouse model of MTLE.

PMID- 19175394
TI  - The effects of right and left amygdala kindling on the female reproductive system
      in rats.
AB  - PURPOSE: Women with epilepsy often have comorbid reproductive dysfunction. Using
      the amygdala kindling model in rats, the present study examined the effects of
      seizures of limbic origin on the reproductive system. METHODS: Female Wistar rats
      were kindled from the left or right basolateral amygdala to a criterion of 40
      stage V seizures. Sham-kindled subjects were handled but not stimulated. Vaginal
      cytology was assessed daily for the duration of the study. Twenty-four hours
      following the last kindled seizure, kindled subjects and their yoked controls
      were sacrificed and their brains and serum were extracted. RESULTS: Kindled
      subjects displayed significantly more abnormal estrous cycle days and
      significantly elevated levels of estradiol as compared to controls. There was,
      however, no total suppression of cycling. No laterality effects were seen for
      estrous cycle abnormalities. DISCUSSION: Seizures of limbic origin cause changes
      in estrous cycling. Right and left kindling seem to have a similar effect. These
      findings highlight the need for clinicians to monitor reproductive issues among
      individuals with epilepsy.

PMID- 19175395
TI  - Palilalia, echolalia, and echopraxia-palipraxia as ictal manifestations in a
      patient with left frontal lobe epilepsy.
AB  - Palilalia is a relatively rare pathologic speech behavior and has been reported
      in various neurologic and psychiatric disorders. We encountered a case of
      palilalia, echolalia, and echopraxia-palipraxia as ictal phenomena of left
      frontal lobe epilepsy. A 55-year-old, right-handed man was admitted because of
      frequent episodes of rapid reiteration of syllables. Video-electroencephalography
      monitoring revealed stereotypical episodes of palilalia accompanied by rhythmic
      head nodding and right-arm posturing with ictal discharges over the left
      frontocentral area. He also displayed echolalia or echopraxia-palipraxia,
      partially responding to an examiner's stimulus. Magnetic resonance imaging
      revealed encephalomalacia on the left superior frontal gyrus and ictal single
      photon emission computed tomography showed hyperperfusion just above the lesion,
      corresponding to the left supplementary motor area (SMA), and subcortical nuclei.
      This result suggests that the neuroanatomic substrate involved in the generation
      of these behaviors as ictal phenomena might exist in the SMA of the left frontal
      lobe.

PMID- 19175396
TI  - Focal cortical dysplasia: a genotype-phenotype analysis of polymorphisms and
      mutations in the TSC genes.
AB  - PURPOSE: Focal cortical dysplasia (FCD) is a common cause of pharmacoresistant
      human epilepsy. FCD has frequently been discussed as a "forme fruste" of tuberous
      sclerosis complex (TSC) because of the radiologic and histologic resemblance of
      dysplastic areas to tubers in TSC. Mutations or a germ-line predisposition in
      terms of increased polymorphisms in the TSC genes have been presumed to influence
      the pathogenesis of FCD. A detailed genotype-phenotype analysis of these patients
      has not been performed so far. METHODS: In this study, 33 patients with FCD
      (among them 23 with FCD type 2 and 4 patients with multifocal FCD) were
      investigated (1) clinically as to dermatologic manifestations, retinal hamartoma,
      cardial rhabdomyoma, and renal angiomyolipoma, and (2) genetically by considering
      lesional brain tissue and blood using single strand conformation polymorphism
      (SSCP) electrophoresis and sequencing of the TSC1 and TSC2 genes. RESULTS: In the
      clinical examinations, no subtle features of TSC could be detected in this large
      group of patients with FCD, pointing to the fact that this is a different patient
      group without clinical overlap. Several sequence alterations were found in the
      TSC1 and TSC2 genes in both lesional brain tissue and blood of FCD patients,
      however, in similar frequencies to that of the normal population. Moreover, most
      of these sequence alterations were silent. DISCUSSION: This study shows that FCD
      even multifocal FCD-is not caused by mutations in the TSC genes and seems not to
      be promoted by polymorphisms in the TSC genes. Therefore, FCD cannot be regarded
      as a "forme fruste" of TSC.

PMID- 19175397
TI  - Facial emotion recognition impairment in chronic temporal lobe epilepsy.
AB  - PURPOSE: To evaluate facial emotion recognition (FER) in a cohort of 176 patients
      with chronic temporal lobe epilepsy (TLE). METHODS: FER was tested by matching
      facial expressions with the verbal labels for the following basic emotions:
      happiness, sadness, fear, disgust, and anger. Emotion recognition performances
      were analyzed in medial (n = 140) and lateral (n = 36) TLE groups. Fifty healthy
      subjects served as controls. The clinical and neuroradiologic variables
      potentially affecting the ability to recognize facial expressions were taken into
      account. RESULTS: The medial TLE (MTLE) group showed impaired FER (86% correct
      recognition) compared to both the lateral TLE patients (FER = 93.5%) and the
      controls (FER = 96.4%), with 42% of MTLE patients recording rates of FER that
      were lower [by at least 2 standard deviations (SDs)] than the control mean. The
      MTLE group was impaired compared to the healthy controls in the recognition of
      all basic facial expressions except happiness. The patients with bilateral MTLE
      were the most severely impaired, followed by the right and then the left MTLE
      patients. FER was not affected by type of lesion, number of antiepileptic drugs
      (AEDs), aura semiology, or gender. Conversely, the early onset of
      seizures/epilepsy was related to FER deficits. These deficits were already
      established in young adulthood, with no evidence of progression in older MTLE
      patients. CONCLUSION: These results on a large cohort of TLE patients demonstrate
      that emotion recognition deficits are common in MTLE patients and widespread
      across negative emotions. We confirm that early onset seizures with right or
      bilateral medial temporal dysfunction lead to severe deficits in recognizing
      facial expressions of emotions.

PMID- 19175398
TI  - A substantial number of Rasmussen syndrome patients have increased IgG, CD4+ T
      cells, TNFalpha, and Granzyme B in CSF.
AB  - PURPOSE: We studied the immunologic molecules in cerebrospinal fluid (CSF) and
      discussed their evolutional changes in pediatric patients with Rasmussen syndrome
      (RS). METHODS: CSF samples collected from 27 patients with RS (average onset age,
      7.5 +/- 5.6 years) were studied. Cell count, protein, glucose, albumin, chloride,
      and immunoglobulin G (IgG) levels were measured by conventional methods. Surface
      markers of lymphocytes in CSF were examined by a cell sorter. Granzyme B,
      interferon gamma (IFNgamma), interleukin 4 (IL-4), tumor necrosis factor alpha
      (TNFalpha), and IL-12 in CSF were quantitated by enzyme-linked immunosorbent
      assay (ELISA). Autoantibodies against GluR epsilon2 (NR2B) were examined by
      immunoblot. RESULTS: The data of the first CSF examination showed that IgG levels
      (Mann-Whitney U test, p < 0.01), CD4(+) T cells (p = 0.02), TNFalpha levels (p <
      0.01), and Granzyme B levels (p < 0.01) were elevated compared with disease
      controls. White blood cell count, IFNgamma level, IL-12 level, and Granzyme B
      level were elevated, especially in the early stage of disease. CD4(+) T cells,
      CD8(+) cells, CD3(+) T cells, IgG levels, and TNFalpha levels were elevated at
      all stages of disease evolution. Protein levels and albumin levels were elevated
      in the progressed stage. Autoantibodies against GluR epsilon2 (NR2B) (IgG) were
      found in 50% of patients in the early stage, and the positive rate was low at the
      progressed stage. DISCUSSION: The present findings suggest that complex
      pathophysiologic mechanisms involving CD4(+) T cells and CD8(+) T cells change
      evolutionally during the progression of RS. A crucial cytotoxic process occurs in
      the early stage, and declines in the progressed stage.

PMID- 19175399
TI  - Oral automatisms induced by stimulation of the mesial frontal cortex.
AB  - Extraoperative electrical stimulation is frequently used to identify eloquent
      areas in patients with pharmacoresistant epilepsy who undergo subdural grid
      evaluation for epilepsy surgery. Oral automatisms elicited by cortical
      stimulation have been described in the mesial temporal lobe, but also in the
      mesial frontal lobe, particularly the cingulate gyrus. However oral automatisms
      attributed to stimulation in the superior frontal gyrus without afterdischarges
      have never been reported. Herein we present two patients with right frontal lobe
      epilepsy with oral automatisms induced by electrical stimulation of the right
      mesial superior frontal gyrus.

PMID- 19175400
TI  - Population pharmacokinetics of levetiracetam and dosing recommendation in
      children with epilepsy.
AB  - PURPOSE: To develop a population pharmacokinetic model to evaluate the
      demographic and physiologic determinants of levetiracetam (LEV) pharmacokinetics
      (PK) and to suggest recommended doses of LEV in children. METHODS: LEV PK were
      investigated in a prospective open trial of LEV as adjunctive therapy using a
      population approach performed with NONMEM (Nonlinear Mixed Effects Model) on 170
      LEV concentration-time records and covariate information from 44 children between
      4 and 16 years of age. Possible associations between pharmacokinetic parameters
      and age, gender, body weight, creatinine clearance, and concomitant antiepileptic
      drugs (AEDs) were assessed. The final model was used to perform Monte Carlo
      simulations in order to identify the dosing regimens that should achieve the same
      nominal target concentration range as in adults. RESULTS: LEV PK were well
      described by a one-compartment model with first-order absorption and elimination.
      Both LEV apparent clearance and distribution volume were related to body weight,
      and no pharmacokinetic interaction was observed. Monte Carlo simulations showed
      that a 10mg/kg twice daily (b.i.d.) regimen provides a plasma concentration
      similar to that obtained in adults for the recommended 500 mg b.i.d. starting
      dose, and that a 20 mg/kg b.i.d. regimen would achieve the previously described 6
      20 mg/L target range for the trough concentration. DISCUSSION: Our results
      support the use of a weight-based LEV dosing regimen and provide a basis for a
      recommended pediatric dosage regimen. The relationship between LEV plasma
      concentrations and clinical effect has not been evaluated fully and could differ
      between adults and children. Clinical studies should be able to validate these
      dosing recommendations.

PMID- 19175401
TI  - Glutamine induces epileptiform discharges in superficial layers of the medial
      entorhinal cortex from pilocarpine-treated chronic epileptic rats in vitro.
AB  - PURPOSE: Glutamine (GLN) is a precursor for synthesis of glutamate and gamma
      aminobutyric acid (GABA) and has been found in the cerebrospinal fluid (CSF) at
      mean concentrations of 0.6 mM. Experiments on slices are usually performed in
      artificial CSF (aCSF) kept free of amino acids. Therefore, the role of glutamine,
      particularly in tissue of epileptic animals, remains elusive. METHODS: Using
      extracellular recordings we studied effects of GLN on field potentials and
      stimulus-evoked field responses in the medial entorhinal cortex (MEC) of combined
      entorhinal cortex hippocampal slices from pilocarpine-treated chronic epileptic
      rats and age-matched saline-injected control rats. RESULTS: In presence of GLN
      (0.5 and 2 mM) recurrent epileptiform discharges (REDs) were observed in slices
      from epileptic rats (64% and 80%, respectively), but not in slices from control
      rats. REDs were restricted to the superficial MEC, suppressed by the alpha-Amino
      3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA)/kainate receptor antagonist 6
      cyano-7-nitroquinoxaline-2,3-dione (30 microM), attenuated by the inhibitor of
      neuronal glutamine transporters methylamino-isobutyric acid (10 mM), and
      apparently augmented and prolonged by the GABA(A) receptor antagonist bicuculline
      methiodide (5 microM). In contrast, amplitudes of stimulus evoked nonsynaptic and
      synaptic field responses increased in slices from control rats (+23% and +12% of
      the reference values) and insignificantly less or not in those of epileptic rats
      (+6.5% and -0.25%, respectively). Notably, stimulus-evoked slow negative
      transients confined to slices of epileptic animals were reduced in amplitude (
      18%). DISCUSSION: In combined entorhinal hippocampal slices from chronic
      epileptic animals, GLN induces glutamatergic REDs via neuronal uptake in
      superficial layers of the MEC where inhibitory function seemed to be partially
      preserved.

PMID- 19175402
TI  - Dynamics of glutamatergic synapses in the medial vestibular nucleus of the mouse.
AB  - During sinusoidal rotation or translation, primary vestibular afferents modulate
      their discharge rates at the frequency of motion, effectively transmitting
      frequency-modulated (FM) signals. This study indicates a possible role for
      excitatory synapses in the processing of FM signals by vestibular brainstem
      pathways. Inputs to medial vestibular neurons were activated with FM pulse
      trains, while inhibitory transmission was blocked. The relationship between the
      presynaptic pulse rate and the postsynaptic membrane potential was found to be
      linear within a range of pulse rates. Short-term plasticity was a factor
      contributing to sensitivity at higher modulating frequencies. The amount of low
      pass filtering was correlated with excitatory postsynaptic potential (EPSP)
      shape, which affected temporal summation during the train. Although the NMDA
      component of glutamatergic transmission affected EPSP shape, it made only a minor
      contribution to the dynamics of synaptic transmission. Most responses showed low
      pass filtering over the entire 1-16 Hz range. Overall, excitatory synapses in the
      medial vestibular nucleus contribute a low-pass filter to central vestibular
      processing and complement the high-pass filtering that is introduced both by
      peripheral vestibular dynamics and by the intrinsic dynamics of secondary
      vestibular neurons.

PMID- 19175403
TI  - Transplantation of human embryonic stem cell-derived neural precursor cells and
      enriched environment after cortical stroke in rats: cell survival and functional
      recovery.
AB  - Cortical stem cell transplantation may help replace lost brain cells after stroke
      and improve the functional outcome. In this study, we transplanted human
      embryonic stem cell (hESC)-derived neural precursor cells (hNPCs) or vehicle into
      the cortex of rats after permanent distal middle cerebral artery occlusion
      (dMCAO) or sham-operation, and followed functional recovery in the cylinder and
      staircase tests. The hNPCs were examined prior to transplantation, and they
      expressed neuroectodermal markers but not markers for undifferentiated hESCs or
      non-neural cells. The rats were housed in either enriched environment or standard
      cages to examine the effects of additive rehabilitative therapy. In the
      behavioral tests dMCAO groups showed significant impairments compared with sham
      group before transplantation. Vehicle groups remained significantly impaired in
      the cylinder test 1 and 2 months after vehicle injection, whereas hNPC
      transplanted groups did not differ from the sham group. Rehabilitation or hNPC
      transplantation had no effect on reaching ability measured in the staircase test,
      and no differences were found in the cortical infarct volumes. After 2 months we
      measured cell survival and differentiation in vivo using stereology and confocal
      microscopy. Housing had no effect on cell survival or differentiation. The
      majority of the transplanted hNPCs were positive for the neural precursor marker
      nestin. A portion of transplanted cells expressed neuronal markers 2 months after
      transplantation, whereas only a few cells co-localized with astroglial or
      oligodendrocyte markers. In conclusion, hESC-derived neural precursor transplants
      provided some improvement in sensorimotor function after dMCAO, but did not
      restore more complicated sensorimotor functions.

PMID- 19175404
TI  - Effects of stimulation of the centromedian nucleus of the thalamus on the
      activity of striatal cells in awake rhesus monkeys.
AB  - Although the existence of a massive projection from the caudal intralaminar
      nuclei of the thalamus [i.e. the centromedian (CM) and parafascicular nuclei] to
      the striatum is well documented, the effects of CM activation upon striatal cells
      remain poorly understood. Therefore, we studied the effects of electrical
      stimulation of CM on the electrophysiological activity of striatal neurons, and
      on striatal levels of gamma-aminobutyric acid (GABA) and acetylcholine in rhesus
      monkeys. Striatal cells did not respond to single-pulse stimulation (bipolar
      biphasic stimulation, 175-500 muA), but the large majority of recorded neurons
      responded to burst stimulation (100 Hz, 1 s, 150-175 muA) of CM, often with a
      delay of tens of milliseconds. Striatal phasically active neurons, which likely
      correspond to projection neurons, responded mainly with increases in firing
      (13/28 cells), while tonically active neurons (likely cholinergic interneurons)
      often showed combinations of increases and decreases in firing (24/46 cells). In
      microdialysis studies, CM stimulation led to a reduction of striatal
      acetylcholine levels. This effect was prevented by addition of the GABA-A
      receptor antagonist gabazine to the microdialysis fluid. We conclude that CM
      stimulation frequently results in striatal response patterns with excitatory and
      inhibitory components. Under the conditions chosen here, the specific patterns of
      striatal responses to CM stimulation are likely the result of striatal processing
      of thalamic inputs. Through these indirect effects, local CM stimulation may
      engage large portions of the striatum. These effects may be relevant in the
      interpretation of the therapeutic effects of CM stimulation for the treatment of
      neurological disorders.

PMID- 19175406
TI  - Progesterone reverses 17beta-estradiol-mediated neuroprotection and BDNF
      induction in cultured hippocampal slices.
AB  - Due to the many similarities in mechanisms of action, targets and effects,
      progesterone (P4), estrogen and neurotrophins have been implicated in synaptic
      plasticity as well as in neuroprotection and neurodegeneration. In this study, we
      examined the interactions between 17beta-estradiol (E2) and P4 and brain-derived
      neurotrophic factor (BDNF) on both plasticity and excitotoxicity in rat cultured
      hippocampal slices. First, we evaluated the neuroprotective effects of E2 and P4
      against N-methyl-D-aspartate (NMDA) toxicity in cultured rat hippocampal slices.
      As previously reported, pretreatment with 10 nm E2 (24 h) was neuroprotective
      against NMDA toxicity. However, P4 (10 nm) added 20 h after E2 treatment for 4 h
      reversed its protective effect. In addition, the same E2 treatment resulted in an
      increase in BDNF protein levels as well as in activation of its receptor, TrkB,
      while addition of P4 attenuated E2-mediated increase in BDNF and TrkB levels.
      Furthermore, E2-mediated neuroprotection was eliminated by a BDNF scavenger, TrkB
      Fc. Our results indicate that E2 neuroprotective effects are mediated through the
      BDNF pathway and that, under certain conditions, P4 antagonizes the protective
      effect of estrogen.

PMID- 19175405
TI  - Tectonigral projections in the primate: a pathway for pre-attentive sensory input
      to midbrain dopaminergic neurons.
AB  - Much of the evidence linking the short-latency phasic signaling of midbrain
      dopaminergic neurons with reward-prediction errors used in learning and habit
      formation comes from recording the visual responses of monkey dopaminergic
      neurons. However, the information encoded by dopaminergic neuron activity is
      constrained by the qualities of the afferent visual signals made available to
      these cells. Recent evidence from rats and cats indicates the primary source of
      this visual input originates subcortically, via a direct tectonigral projection.
      The present anatomical study sought to establish whether a direct tectonigral
      projection is a significant feature of the primate brain. Injections of
      anterograde tracers into the superior colliculus of macaque monkeys labelled
      terminal arbors throughout the substantia nigra, with the densest terminations in
      the dorsal tier. Labelled boutons were found in close association (possibly
      indicative of synaptic contact) with ventral midbrain neurons staining positively
      for the dopaminergic marker tyrosine hydroxylase. Injections of retrograde tracer
      confined to the macaque substantia nigra retrogradely labelled small- to medium
      sized neurons in the intermediate and deep layers of the superior colliculus.
      Together, these data indicate that a direct tectonigral projection is also a
      feature of the monkey brain, and therefore likely to have been conserved
      throughout mammalian evolution. Insofar as the superior colliculus is configured
      to detect unpredicted, biologically salient, sensory events, it may be safer to
      regard the phasic responses of midbrain dopaminergic neurons as 'sensory
      prediction errors' rather than 'reward prediction errors', in which case dopamine
      based theories of reinforcement learning will require revision.

PMID- 19175408
TI  - Characterization of Trypanosoma cruzi L-cysteine transport mechanisms and their
      adaptive regulation.
AB  - L-Cysteine and methionine are unique amino acids that act as sulfur donors in all
      organisms. In the specific case of Trypanosomatids, L-cysteine is particularly
      relevant as a substrate in the synthesis of trypanothione. Although it can be
      synthesized de novo, L-cysteine is actively transported in Trypanosoma cruzi
      epimastigote cells. L-Cysteine uptake is highly specific; none of the amino acids
      assayed yield significant differences in terms of transport rates. L-Cysteine is
      transported by epimastigote cells with a calculated apparent K(m) of 49.5 microM
      and a V(max) of about 13 pmol min(-1) per 10(7) cells. This transport is finely
      regulated by amino acid starvation, extracellular pH, and between the parasite
      growth phases. In addition, L-cysteine is incorporated post-translationally into
      proteins, suggesting its role in iron-sulfur core formation. Finally, the
      metabolic fates of Lcysteine were predicted in silico.

PMID- 19175407
TI  - Bilateral motor unit synchronization of leg muscles during a simple dynamic
      balance task.
AB  - To handle the rich repertoire of behavioural goals, the CNS has to control the
      many degrees of freedom of the musculoskeletal system in a flexible manner. This
      problem can be drastically simplified if muscle synergies serve as the to-be
      controlled building blocks of motor performance, instead of the individual
      degrees of freedom. Muscle synergies have been identified as coherent activation
      patterns of a group of muscles in space or time, but the neural mechanisms
      underlying their formation remain largely unknown. Here we evaluated the
      hypothesis that synergies are reflected in common input to different contributing
      muscles, and investigated modulations in motor unit (MU) synchronization of
      homologous muscles during a rhythmic balance task. If common input is related to
      muscle synergies, the resultant MU synchronization should not be static but task
      dependent and, in the present context, vary in time. Coherence between surface
      electromyographic signals of bilateral leg muscles revealed MU synchronization in
      two distinct frequency bands. MU synchronization was not constant but modulated
      within a movement cycle, and its time course resembled the activation patterns of
      the muscles. These results are congruent with a linkage between MU
      synchronization and muscle synergies, and suggest that MU synchronization
      provides an expedient method for studying synergy-related neural mechanisms.

PMID- 19175409
TI  - Carbon isotope-labelling experiments indicate that ladderane lipids of anammox
      bacteria are synthesized by a previously undescribed, novel pathway.
AB  - Ladderane lipids are unusual membrane lipids of bacteria that anaerobically
      oxidize ammonium to dinitrogen gas (anammox). Ladderane lipids contain linearly
      concatenated cyclobutane rings for which the pathway of biosynthesis is currently
      unknown. To investigate the possible biosynthetic routes of these lipids, 2-(13)C
      labelled acetate was added to a culture of the anammox bacterium Candidatus
      Brocadia fulgida. Labelling patterns obtained by high-field (13)C nuclear
      magnetic resonance spectroscopy of isolated lipids indicated that C. Brocadia
      fulgida synthesizes C(16:0) and isoC(16:0) fatty acids according to the known
      pathway of type II fatty acid biosynthesis. The (13)C-labelling pattern of the
      C(8) alkyl chain of the C(20) [3] ladderane monoether also indicated the use of
      this route. However, carbon atoms in the cyclobutane rings and the cyclohexane
      ring were nonspecifically labelled and did not correspond to known patterns of
      fatty acid synthesis. Taken together, our results indicate that it is unlikely
      that ladderane lipids are formed from the cyclization of polyunsaturated fatty
      acids as hypothesized previously and suggest an alternative, although as yet
      unknown, pathway of biosynthesis.

PMID- 19175410
TI  - The complex and dynamic genomes of industrial yeasts.
AB  - The Saccharomyces sensu stricto genus contains many species that are industrially
      important for fermentation of wines, beers and ales. The molecular
      characterization of the genomes of yeasts involved in these processes reveals
      that the majority arose from interspecific hybridization between two and
      sometimes three yeast species. The hybridization events generated allopolyploid
      genomes, and subsequent recombination events between the parental genomes
      resulted in the formation of mosaic chromosomes. The polyploid and hybrid nature
      of the genomes confers robust characteristics such as tolerance to environmental
      stress to these industrial yeasts and provides a means for adaptive evolution.

PMID- 19175411
TI  - Detergent fractionation with subsequent subtractive suppression hybridization as
      a tool for identifying genes coding for plasma membrane proteins.
AB  - The identification of tumor-specific proteins located at the plasma membrane is
      hampered by numerous methodological pitfalls many of which are associated with
      the post-translational modification of such proteins. Here, we present a new
      combination of detergent fractionation of cells and of subtractive suppression
      hybridization (SSH) to gain overexpressed genes coding for membrane-associated or
      secreted proteins. Fractionation of subcellular components by digitonin allowed
      sequestering mRNA of the rough Endoplasmatic reticulum and thereby increasing the
      percentage of sequences coding for membrane-bound proteins. Fractionated mRNAs
      from the cutaneous T-cell lymphoma (CTCL) cell line HuT78 and from normal
      peripheral blood monocytes were used for SSH leading to the enrichment of
      sequences overexpressed in the tumor cells. We identified some 21 overexpressed
      genes, among them are GPR137B, FAM62A, NOMO1, HSP90, SLIT1, IBP2, CLIF, IRAK and
      ARC. mRNA expression was tested for selected genes in CTCL cell lines, skin
      specimens and peripheral blood samples from CTCL patients and healthy donors.
      Several of the detected sequences are clearly related to cancer, but have not yet
      been associated with CTCL. qPCR confirmed an enrichment of these mRNAs in the
      rough endoplasmic reticulum fraction. RT-PCR confirmed the expression of these
      genes in skin specimens and peripheral blood of CTCL patients. Western blotting
      verified protein expression of HSP90 and IBP2 in HuT78. GPR137B could be detected
      by immunohistology in HuT78 and in keratinocytes of dysplastic epidermis, but
      also in sweat glands of healthy skin. In summary, we developed a new technique,
      which allows identifying overexpressed genes coding preferentially for membrane
      associated proteins.

PMID- 19175413
TI  - Candida albicans ABG1 gene is involved in endocytosis.
AB  - The human fungal pathogen Candida albicans undergoes reversible morphogenetic
      transitions between yeast, hyphal and pseudohyphal forms. The fungal vacuole
      actively participates in differentiation processes and plays a key role
      supporting hyphal growth. The ABG1 gene of C. albicans encodes an essential
      protein located in the vacuolar membranes of both yeast and hyphae. Using
      fluorescence microscopy of a green fluorescent protein-tagged version of Abg1p, a
      fraction of the protein was detected in hyphal tips, not associated with vacuolar
      membranes. Live cell imaging of emerging germ tubes showed that Abg1p migrated to
      the polarized growth site and colocalized with endocytic vesicles. Phenotypic
      analysis of a methionine-regulated conditional mutant confirmed that Abg1p is
      involved in endocytosis.

PMID- 19175414
TI  - Secondary cell wall formation in Cryptococcus neoformans as a rescue mechanism
      against acid-induced autolysis.
AB  - Growth of the opportunistic yeast pathogen Cryptococcus neoformans in a synthetic
      medium containing yeast nitrogen base and 1.0-3.0% glucose is accompanied by
      spontaneous acidification of the medium, with its pH decreasing from the initial
      5.5 to around 2.5 in the stationary phase. During the transition from the late
      exponential to the stationary phase of growth, many cells died as a consequence
      of autolytic erosion of their cell walls. Simultaneously, there was an increase
      in an ecto-glucanase active towards beta-1,3-glucan and having a pH optimum
      between pH 3.0 and 3.5. As a response to cell wall degradation, some cells
      developed an unusual survival strategy by forming 'secondary' cell walls
      underneath the original ones. Electron microscopy revealed that the secondary
      cell walls were thicker than the primary ones, exposing bundles of polysaccharide
      microfibrils only partially masked by an amorphous cell wall matrix on their
      surfaces. The cells bearing secondary cell walls had a three to five times higher
      content of the alkali-insoluble cell wall polysaccharides glucan and chitin, and
      their chitin/glucan ratio was about twofold higher than in cells from the
      logarithmic phase of growth. The cell lysis and the formation of the secondary
      cell walls could be suppressed by buffering the growth medium between pH 4.5 and
      6.5.

PMID- 19175412
TI  - Roles of DNA adenine methylation in host-pathogen interactions: mismatch repair,
      transcriptional regulation, and more.
AB  - The DNA adenine methyltransferase (Dam methylase) of Gammaproteobacteria and the
      cell cycle-regulated methyltransferase (CcrM) methylase of Alphaproteobacteria
      catalyze an identical reaction (methylation of adenosine moieties using S
      adenosyl-methionine as a methyl donor) at similar DNA targets (GATC and GANTC,
      respectively). Dam and CcrM are of independent evolutionary origin. Each may have
      evolved from an ancestral restriction-modification system that lost its
      restriction component, leaving an 'orphan' methylase devoted solely to epigenetic
      genome modification. The formation of 6-methyladenine reduces the thermodynamic
      stability of DNA and changes DNA curvature. As a consequence, the methylation
      state of specific adenosine moieties can affect DNA-protein interactions. Well
      known examples include binding of the replication initiation complex to the
      methylated oriC, recognition of hemimethylated GATCs in newly replicated DNA by
      the MutHLS mismatch repair complex, and discrimination of methylation states in
      promoters and regulatory DNA motifs by RNA polymerase and transcription factors.
      In recent years, Dam and CcrM have been shown to play roles in host-pathogen
      interactions. These roles are diverse and have only partially been understood.
      Especially intriguing is the evidence that Dam methylation regulates virulence
      genes in Escherichia coli, Salmonella, and Yersinia at the posttranscriptional
      level.

PMID- 19175415
TI  - The influence of yeast oxygenation prior to brewery fermentation on yeast
      metabolism and the oxidative stress response.
AB  - Yeast preoxygenation can confer important advantages to brewery fermentations by
      means of omitting the need to oxygenate the wort. However, the impact of yeast
      preoxygenation on yeast metabolism has never been assessed systematically.
      Therefore, expression analysis was performed of genes that are of importance in
      oxygen-dependent pathways, oxidative stress response and general stress response
      during 8 h of preoxygenation. The gene expressions of both the important
      transcription factors Hap1 and Rox1, involved in oxygen sensing, were mainly
      increased in the first 3 h, while YAP1 expression, which is involved in the
      oxidative stress response, increased drastically only in the first 45 min. The
      results also show that stress-responsive genes (HSP12, SSA3, PAU5, SOD1, SOD2,
      CTA1 and CTT1) were induced during the process, together with the accumulation of
      trehalose. The accumulation of ergosterol and unsaturated fatty acids was
      accompanied by the expression of ERG1, ERG11 and OLE1. Genes involved in
      respiration (QCR9, COX15, CYC1 and CYC7) also increased during preoxygenation.
      Yeast viability did not decrease during the process, and the fermentation
      performance of the yeast reached a maximum after 5 h of preoxygenation. These
      results suggest that yeast cells acquire a stress response along the
      preoxygenation period, which makes them more resistant against the stressful
      conditions of the preoxygenation process and the subsequent fermentation.

PMID- 19175416
TI  - Conservation and dispersion of sequence and function in fungal TRK potassium
      transporters: focus on Candida albicans.
AB  - TRK proteins - essential potassium (K(+)) transporters in fungi and bacteria, as
      well as in plants - are generally absent from animal cells, which makes them
      potential targets for selective drug action. Indeed, in the human pathogen
      Candida albicans, the single TRK isoform (CaTrk1p) has recently been demonstrated
      to be required for activity of histidine-rich salivary antimicrobial peptides
      (histatins). Background for a detailed molecular investigation of TRK-protein
      design and function is provided here in sequence analysis and quantitative
      functional comparison of CaTrk1p with its better-known homologues from
      Saccharomyces cerevisiae. Among C. albicans strains (ATCC 10261, SC5314, WO-1),
      the DNA sequence is essentially devoid of single nucleotide polymorphisms in
      regions coding for evolutionarily conserved segments of the protein, meaning the
      four intramembranal [membrane-pore-membrane (MPM)] segments thought to be
      involved directly with the conduction of K(+) ions. Among 48 fungal (ascomycete)
      TRK homologues now described by complete sequences, clades (but not the detailed
      order within clades) appear conserved for all four MPM segments, independently
      assessed. The primary function of TRK proteins, 'active' transport of K(+) ions,
      is quantitatively conserved between C. albicans and S. cerevisiae. However, the
      secondary function, chloride efflux channeling, is present but poorly conserved
      between the two species, being highly variant with respect to activation
      velocity, amplitude, flickering (channel-like) behavior, pH dependence, and
      inhibitor sensitivity.

PMID- 19175417
TI  - Immune tolerance induction with high von Willebrand factor/factor VIII content
      ratio concentrate in children with haemophilia A and high-responding inhibitor.

PMID- 19175418
TI  - Activated prothrombin complex concentrate for acquired haemophilia when
      recombinant factor VIIa fails.

PMID- 19175419
TI  - The plasma concentration of activated protein C appears normal in patients with
      haemophilia.
AB  - Increased concentration of activated protein C (APC) has been observed in
      patients with thromboembolic disorders, but whether the level of APC in patients
      with bleeding disorders is decreased remains unknown. Seventy patients with
      haemophilia A or B with mild, moderate or severe form were studied. Detailed
      information on bleeding, arthropathy and factor consumption was collected during
      a 10-year period. The clinical severity of the disease was expressed as the
      Hemophilia Severity Score (HSS). Plasma concentration of APC was measured as APC
      in complex with protein C inhibitor. The median concentration of APC-PCI complex
      in patients with haemophilia was 0.14 microg L(-1) and it did not differ between
      the types and forms. In 16 patients with severe haemophilia A and the inversion
      mutation in intron 22, there was no correlation between clinical severity and the
      concentration of APC-PCI complex. Patients with haemophilia appear to generate
      normal concentrations of APC during basal conditions. APC does not seem to be an
      important modulator of the phenotypic expression of haemophilia.

PMID- 19175420
TI  - Successful control of bleeding during supracondylar amputation caused by severe
      compartment syndrome in patient with haemophilia A and high titre of inhibitor.

PMID- 19175421
TI  - Management of haemophilic pseudotumours with special emphasis on radiotherapy and
      arterial embolization.
AB  - The haemophilic pseudotumour is an expanding destructive haematoma, which is
      associated with a considerable amount of morbidity in haemophilic patients. Its
      prevention is paramount. In fact, this goal can be achieved by primary
      prophylaxis to avoid muscle haematomas and by adequate and long-term
      haematological treatment of muscle haematomas in case they appear. At the moment,
      surgical excision of pseudotumour is the preferred treatment by many authors.
      However, there are instances that surgical extraction of the lesion is not
      feasible. In such situations, radiotherapy and arterial embolization should be
      considered either alone or as an adjunct to surgery. Conservative management
      using a combination of radiotherapy and replacement therapy should be considered
      for treating haemophilic bone pseudotumours, which are located in the skull or in
      the distal parts of the limbs, especially in conditions where some impediments to
      surgical excision exist. In fact, the radiation should be delivered to the lesion
      site in small fragments of 2 Gy or less to a total dosage of 6-23.5 Gy, which is
      the most recommended radiation dosage, at the moment. Therapeutic arterial
      embolization of haemophilic pseudotumours should be considered in lesions of
      large size, especially in pseudotumours of pelvic region, as it may effectively
      reduce its size and decrease the risk of bleeding complications during surgery.
      Nevertheless, in view of its temporary effect, embolization may better be
      performed, as a preparatory procedure, at best about 2 weeks prior to surgery.
      This time lapse will allow for mass shrinkage but is insufficient for vessel
      restoration.

PMID- 19175422
TI  - Occurrence, course and risk factors of depression during antiviral treatment for
      chronic hepatitis C in patients with inherited bleeding disorders: a prospective
      study.
AB  - Treatment of hepatitis C virus (HCV) consists of pegylated interferon (IFN)-alpha
      and ribavirin for 24 or 48 weeks. An important side-effect of IFN-alpha is
      depression. The occurrence, course and risk factors of depression during
      antiviral treatment were studied prospectively in HCV patients with inherited
      bleeding disorders. The Beck Depression Inventory, indicating no, mild, moderate
      or severe depression, was administered to 47 patients before starting therapy,
      after 4, 12, 24 and 48 weeks of treatment, and 4 weeks after cessation of
      therapy. At baseline, five patients (11%) had mild depression. Depression
      worsened during treatment in three of these patients. In all five patients,
      (mild) depression persisted 4 weeks after treatment. Of the remaining 42
      patients, 23 (55%) developed depression during treatment (14 mild, eight moderate
      and one severe), mostly (78%) during the first 12 weeks. Four weeks after
      cessation of treatment, three of 23 patients still had mild depression. The only
      independent risk factor for development of depression was a history of depression
      or other psychiatric problems (odds ratio 9.7). For patients with inherited
      bleeding disorders, depression is a significant, mostly transient, problem during
      HCV treatment. We recommend close monitoring of patients, especially those with
      previous psychiatric problems, to ensure adequate detection and treatment of
      depression during antiviral therapy.

PMID- 19175423
TI  - Laboratory performance in the World Federation of Hemophilia EQA programme, 2003
      2008.
AB  - External quality assessment (EQA) has been shown to improve laboratory
      performance and diagnosis in haemostasis. We report here findings from the World
      Federation of Haemophilia (WFH) EQA programme during the period 2004-2007.
      Samples for PT, APTT, FVIII:C, FIX:C and VWF assays were distributed to centres
      in both established and emerging countries, and results were compared with
      results obtained by United Kingdom National External Quality Assessment Scheme
      (UK NEQAS) participants on the same samples. In general, good agreement was seen
      throughout between WFH and UK NEQAS for screening tests, and it was possible to
      identify an improvement in WFH centre agreement for results for VWF assays during
      the period of study. Agreement between emerging and established WFH centres was
      comparable for screening tests, possibly indicative of the relative simplicity of
      these tests and the degree of automation now employed in almost all haemostasis
      laboratories. However, CVs and performance compared with UK NEQAS participant
      results for factor assays amongst established centres was better than between
      emerging centres. Distribution of a questionnaire revealed different application
      of methodology for these assays, which may contribute to the observed difference
      in performance. Several centres participated in supplementary exercises, with
      comparable results obtained by emerging and established centres performing FVIII
      and fibrinogen measurement on cryoprecipitate, and all centres performing FVIII
      inhibitor assays correctly identifying the presence of an inhibitor.
      Participation in EQA programmes should continue to encourage improvement in
      laboratory performance and therefore improvements in the diagnosis and care of
      patients with haemophilia.

PMID- 19175424
TI  - The prevalence of headache and its association with socioeconomic status among
      schoolchildren in istanbul, Turkey.
AB  - OBJECTIVE: The etiology and pathogenesis of migraine and other types of headache
      are still under discussion. An interaction of organic, psychological, and
      psychosocial factors is operative. In this study, we aimed to determine the
      prevalence of headache and its association with socioeconomic status among
      schoolchildren. STUDY DESIGN: A cross-sectional study was performed on 2669
      schoolchildren via a parental questionnaire. Socioeconomic status was determined
      according to the Turkish socioeconomic status scale. RESULTS: The mean age of the
      students was 8.2 +/- 2.4 years. The headache prevalence was 46.2% (95% CI: 44.3
      48.1). The prevalence of migraine was 3.4% (95% CI: 2.8-4.1), the prevalence of
      probable migraine was 8.7% (95% CI: 7.6-9.8), and that of non-migraine headache
      was 34.1% (95% CI: 32.3-35.9). Multivariate analysis revealed that older age,
      being a girl, having a family history of headache, and exposure to passive
      smoking at home were independently associated with headache. There was an inverse
      association between socioeconomic status and all 3 types of headaches after
      adjusting for age, sex, family history of headache, and presence of passive
      smoking. When the group with the lowest socioeconomic status was taken as the
      reference category, the odds ratios for the highest socioeconomic group were 0.33
      (95% CI: 0.16-0.69, P = .003) for the migraine, 0.30 (95% CI: 0.11-0.89, P =
      .029) for the probable migraine, and 0.34 (95% CI: 0.16-0.72, P = 0.005) for the
      non-migraine headache. CONCLUSION: Headache is more common among children with
      lower socioeconomic groups. Social causation can play a role in the pathogenesis
      of headache.

PMID- 19175426
TI  - 'Nobody ever chooses this ...': a qualitative study of service providers working
      in the sexual violence sector - key issues and challenges.
AB  - This paper describes the findings from the first stage of a study designed to
      assess the impact of sexual violence (SV) on the lives of Irish women.
      Stakeholder interviews (n = 18) were undertaken to explore experiences of
      delivering services to people who have experienced SV, in rural and urban
      settings in Ireland. A range of themes and sub-themes were identified through a
      thematic analysis, and interrelationships between two of the main themes
      (barriers to services and current gaps in service provision) are discussed. Sub
      themes include: survivor guilt and shame, difficulties in naming the incident as
      SV, problems with the Criminal Justice System and the availability of Sexual
      Assault Treatment Units. Participants identified an urgent need for a co
      ordinated national strategy in the form of a public awareness and education
      campaign in order to undermine commonly held rape myths and stereotypes. The
      findings will be of interest to all health and social care professionals who are
      in contact with women who have experienced SV. They will also help to raise an
      awareness of the 'hidden' costs of SV, and inform appropriate policies and
      community-based responses to this important social problem.

PMID- 19175427
TI  - 'Out of Hospital': a scoping study of services for carers of people being
      discharged from hospital.
AB  - Successive government policies have highlighted the need to inform and involve
      carers fully in the hospital discharge process. However, some research suggests
      that many carers feel insufficiently involved and unsupported in this process.
      This paper summarises a scoping review to identify what the UK literature tells
      us about the service provision for carers, and its effectiveness, around the time
      of hospital discharge of the care recipient, and also describes a mapping
      exercise of the work currently being done by Princess Royal Trust for Carers
      Centres in England to support carers around the time of hospital discharge. The
      restriction to UK literature was dictated by the nature of the project; a modest
      review carried out for a UK-based voluntary sector organization. Fifty-three
      documents were reviewed, of which 19 papers (representing 17 studies) were
      reporting on primary research. As only five of these studies actually involved an
      intervention, it appears there is very little research from the UK which
      evaluates specific interventions to support carers around the time of hospital
      discharge of the care recipient. While the mapping exercise showed that in some
      areas there are services and/or initiatives in place which have been designed to
      improve the process of discharge for carers, in many places there is still a gap
      between what policy and research suggest should happen and what actually happens
      to carers at this time. Even where services and initiatives to support carers
      through the discharge process exist, there is only limited evidence from research
      or evaluation to demonstrate their impact on the carer's experience. Further
      research, both quantitative and qualitative, is required to address these areas
      and enable commissioners, providers and carers' organizations to work together
      towards a service in which patients and carers alike receive the support and help
      they need at this significant time of transition.

PMID- 19175428
TI  - Enabling independence: restorative approaches to home care provision for frail
      older adults.
AB  - This study reviews the 'real world' potential (i.e. efficacy and effectiveness)
      of restorative approaches towards home care for frail older adults. Such
      approaches aim to go beyond traditional home care goals of 'maintenance' and
      'support' towards improvements in functional status and quality of life. Our
      review of the literature included searches of health and gerontology databases as
      well as 'grey literature' across Australia, the UK and the USA. We provide an
      initial overview of the efficacy of a range of single component restorative
      interventions, including occupational therapy, physical therapy, health education
      and social rehabilitation. In order to answer questions about the overall
      efficacy and cost-effectiveness of restorative home care provision, we also
      review the nature of in-house programmes across the three nations as well as the
      evidence base for such programmes, particularly when they have been compared to
      home care 'as usual'. A range of positive outcomes has emerged, including
      improved quality of life and functional status and reduced costs associated with
      a reduction in the ongoing use of home care services postintervention. Questions
      remain about which components are most beneficial, which clients are likely to
      receive the greatest benefit, and the appropriate intensity and duration of such
      interventions.

PMID- 19175429
TI  - Speculations on the molecular structure of eumelanin.
AB  - Eumelanin is the polymeric black pigment commonly found in hair and skin. Its
      chemical intractability, to all but vigorous oxidizing agents, has hindered
      satisfactory understanding of its molecular structure. It is well-established
      that the immediate precursor to polymerization, indole-5,6-quinone (IQ), is
      biosynthesized from the amino acid tyrosine. Current views are that the polymer
      consists of single bond connections between random indole and degraded indole
      units. In this paper, an alternative chemical scheme for the polymerization of IQ
      is proposed based upon the original suggestion by Horner in 1949 that a Diels
      Alder (D-A) reaction might be involved. The proposed basic chemical scheme for
      eumelanin formation is that D-A addition occurs specifically between the 2- and 3
      positions of one IQ molecule and the 7- and 4- positions respectively of a second
      IQ molecule, that the ensuing diketo bridge is oxidized to carboxyl groups and
      that, by decarboxylation and aromatization, a fused indole dimer is produced. It
      is envisaged that, by further D-A addition of more IQ molecules, oligomers of
      greater molecular mass are produced. Calculations based on published bond lengths
      and angles for the indole nucleus show that oligomeric units containing a total
      of up to 11 fused indoles could be packed into a flat circular disc of 20 A
      diameter. The discs of the extensively conjugated polymer are envisaged to be
      stacked above each other by pi-pi interaction and with a spacing of 3.4 A to
      produce cylindrical units, the mass density of which is calculated to be 1.54 gm
      cm(-3); approximating with actual physical measurements. The size and shape of
      the predicted cylinders are in concordance with those observed in atomic force
      microscope investigations of eumelanin proto-particles. The model is also in
      agreement with published experimental data that 2/3rds of the carbon dioxide
      liberated during eumelanin formation derives from positions 5- and 6- of the IQ
      molecule.

PMID- 19175430
TI  - Methodology to improve epidermal barrier homeostasis: how to accelerate the
      barrier recovery?
AB  - Good water-impermeable barrier function is vital for healthy skin. Abnormality of
      the barrier function is observed in a variety of skin diseases, such as atopic
      dermatitis, psoriasis and contact dermatitis. Moreover, repeated barrier
      disruption induces epidermal hyperplasia and inflammation. On the other hand,
      acceleration of the barrier recovery prevents epidermal hyperplasia induced by
      barrier disruption in a dry environment. Thus, methods to improve the barrier
      function are very important for clinical dermatology. Recently, we have been
      searching for new reagents and/or new materials to improve barrier homeostasis.
      In this review, I will describe our recent findings and show how they provide the
      basis for a new perspective for clinical dermatology.

PMID- 19175431
TI  - Development of clay liquid detergent for Islamic cleansing and the stability
      study.
AB  - Clay liquid detergents (CLDs) were developed for cleansing religiously-prohibited
      dirt ('najis') according to Islamic law. Four types of clay were selected: marl,
      kaolin, bentonite and veegum. After product development trials, five CLD
      formulations with varying combinations of clays were qualified for stability
      testing. Three exaggerated temperature conditions were considered: 4 degrees C
      for 24 h, 50 degrees C for 7 days, and 40 degrees C for 1 month. The CLDs were
      also evaluated at 30, 60 and 90 days after production, while being stored at room
      temperature (RT30, RT60 and RT90). Physical and chemical characteristics
      including pH, colour, viscosity, surface tension, foam tests and sensory liking
      scores were evaluated. Our results showed that the kaolin-based formula, F2, had
      an optimal pH (closest to skin pH) of 5.08. The other formulas ranged from pH 6
      to 8. Colour shades of the CLDs ranged from white, to creamy white, to mildly
      greenish-white. The foaming properties of the CLDs, the means +/- SD of foam
      heights at 0 and 5 min, using the Ross-Miles test, were 19.13 +/- 0.25 to 20.88
      +/- 0.45 cm at RT90 and were comparable with those of commercial detergents. Foam
      stability of all CLDs was high, as shown from the foam heights between 0 and 5
      min being not significantly different (P > 0.05). The surface tensions, means +/-
      SD, of CLD solutions were between 27.94 +/- 0.08 and 28.72 +/- 0.04 mN m(-1),
      which were slightly better than the surface tension of 29.08 +/- 0.04 mN m(-1)
      for sodium lauryl sulphate. There was a weak negative relationship between
      surface activity and foam height, based on the pooled data of the CLDs (R(2) =
      0.209, P < 0.01). The viscosity of four CLDs ranged from 16 317 to 49 036 mPa s.
      In conclusion, CLDs can be formulated with good stability. F2 (kaolin-based, with
      a white, creamy texture) was the best CLD formula. It had the highest surface
      activity, moderate lathering and pleasant physical appearance.

PMID- 19175432
TI  - Quartz plates for determining sun protection in vitro and testing photostability
      of commercial sunscreens.
AB  - Testing plate made of optical quartz has been developed for the purpose of
      determination of sun protection factor (SPF)(in vitro) by the method of diffusion
      transmission spectroscopy; the plates were coarsened by sanding and grinding to
      surface roughness values (Ra) of 18 mum. The plate was coated with a film of
      sunscreen by an application of 2 mg cm(-2) as that used for determination of
      SPF(in vivo) by the COLIPA method. The transmission values measured were
      converted into the SPF(in vitro) and the protection factor in ultraviolet A
      light, UVAPF(in vitro). The testing plate was tested with commercial sunscreens.
      The found values of SPF(in vitro) fit well with the values determined by means of
      the COLIPA method in vivo. The plates coated with sunscreen film were irradiated
      with light simulating the sun radiation. The values of protection factors
      obtained before and after irradiation were compared, and the differences were
      used for estimation of photostability of the UV filters included.

PMID- 19175433
TI  - Closed-chamber transepidermal water loss measurement: microclimate, calibration
      and performance.
AB  - The importance of transepidermal water loss (TEWL) as a measure of the skin
      barrier is well recognized. Currently, the open-chamber method is dominant, but
      it is increasingly challenged by newer closed-chamber technologies. Whilst there
      is familiarity with open-chamber characteristics, there is uncertainty about the
      capabilities of the challengers. The main issues are related to how microclimate
      affects TEWL measurements. The aim of this paper is to provide a framework for
      understanding the effects of microclimate on TEWL measurement. Part of the
      problem is that TEWL measurement is indirect. TEWL is the diffusion of condensed
      water through the stratum corneum (SC), whereas TEWL methods measure water vapour
      flux in the air above the SC. This vapour flux depends on (i) the rate of supply
      of water to the skin surface and (ii) the rate of evaporation of water from the
      skin surface. Rate (i) is a skin property (TEWL), rate (ii) is a microclimate
      property. The controlling rate for the combined process is the lower of the above
      two rates. Therefore, TEWL instruments measure TEWL only when TEWL is the rate
      limiting process. Another problem is that SC barrier property and SC hydration
      are affected by the microclimate adjacent to the skin surface. This is discussed
      insofar as it affects the measurement of TEWL. The conclusion is that such
      changes occur on a timescale that is long compared with TEWL measurement times.
      An important aspect of TEWL measurement is calibration. We present an analysis of
      the traditional wet-cup method and a new droplet method that is traceable and has
      been independently verified by a standards laboratory. Finally, we review
      performance indicators of commercial closed-chamber instruments with reference to
      open-chamber instruments. The main findings are that TEWL readings correlate
      well, but there are significant differences in the other aspects of performance.

PMID- 19175434
TI  - Factors associated with place of death for elderly Japanese-American men: the
      Honolulu Heart Program and Honolulu-Asia Aging Study.
AB  - Place of death is an indicator of health service utilization at the end of life
      and differs according to cause of death. Asian Americans may have a higher
      percentage of hospital deaths than Caucasian Americans, yet reasons for this
      finding are unclear. This study examined distribution of place of death and the
      associations between place and cause of death in elderly Japanese-American men in
      a longitudinal cohort: the Honolulu Heart Program and Honolulu-Asia Aging Study.
      Data collected between 1991 and 1999 on 1,352 men aged 73 to 99 at death were
      analyzed for associations between cause-of-death characteristics and hospital,
      home, or nursing home location of death. Fifty-nine percent of men died in
      hospitals, 23% died at home, and 18% died in nursing homes. Of the dementia
      related deaths, 43% occurred in hospitals (vs 16% in a national study), 37%
      occurred in nursing homes (vs 67% in a national study), and 20% occurred at home.
      Of the stroke deaths, 53% occurred in hospitals, 40% were in nursing homes, and
      7% occurred at home. Of the cancer deaths, 53% occurred in hospitals, 34%
      occurred at home, and 13% were in nursing homes. Traditional family obligation to
      care for elderly people at home and inability to access care for dementia may
      account for the greater rate of hospital death and lower rate of nursing home
      deaths in this cohort. Attitudes of elderly Japanese Americans and their families
      regarding place of care at the end of life, particularly in the setting of
      dementia, merit future study.

PMID- 19175435
TI  - Persistent racial and ethnic disparities in up-to-date colorectal cancer testing
      in medicare enrollees.
AB  - OBJECTIVES: To assess whether greater colonoscopy use among white as compared
      with nonwhite Medicare enrollees since Medicare established coverage for
      colorectal cancer (CRC) screening has been associated with a widening in white
      versus nonwhite disparities in up-to-date CRC testing status. DESIGN: Serial
      cross-sectional analysis of Medicare claims. SETTING: Surveillance, Epidemiology,
      and End Results (SEER) regions in nine states, representing 14% of the U.S.
      population. PARTICIPANTS: A 5% random sample of fee-for-service Medicare
      enrollees aged 70 to 79 within each 6-month period from mid-1995 through 2003.
      MEASUREMENTS: Trends in up-to-date status (having a fecal occult blood test
      (FOBT) claim in the prior year or a sigmoidoscopy or colonoscopy claim in the
      prior 5 years) according to race or ethnicity, estimated using repeated-measures
      logistic regression adjusting for age, sex, rural versus urban residence, income,
      comorbidity, and SEER region. RESULTS: From mid-1995 through 2003, the adjusted
      percentage of enrollees that were up-to-date increased by a similar magnitude in
      whites (from 39.4% to 47.3%), blacks (from 29.0% to 38.1%), Asians and Pacific
      Islanders (from 33.1% to 41.8%), and Hispanics (from 23.7% to 33.2%). Although
      white versus nonwhite disparities in up-to-date status via colonoscopy widened,
      this was counterbalanced by narrowing white versus nonwhite disparities in up-to
      date status via FOBT and sigmoidoscopy. CONCLUSION: White versus nonwhite
      disparities in up-to-date CRC testing status in Medicare enrollees largely
      persisted through 2003.

PMID- 19175436
TI  - Body mass index and risk of adverse cardiac events in elderly patients with hip
      fracture: a population-based study.
AB  - OBJECTIVES: To determine whether obesity affects cardiac complications after hip
      fracture repair. DESIGN: A population-based historical study using data from the
      Rochester Epidemiology Project. SETTING: Olmsted County, Minnesota. PARTICIPANTS:
      All urgent hip fracture repairs between 1988 and 2002. MEASUREMENTS: Body mass
      index (BMI) was categorized as underweight (<18.5 kg/m(2)), normal-weight (18.5
      24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), and obese (>or=30 kg/m(2)).
      Postoperative cardiac complications were defined as myocardial infarction, angina
      pectoris, congestive heart failure, or new-onset arrhythmias within 1-year of
      surgery. Incidence rates were estimated for each outcome, and overall cardiac
      complications were assessed using Cox proportional hazards models adjusted for
      age, sex, year of surgery, use of beta-blockers, and the Revised Cardiac Risk
      Index. RESULTS: Hip fracture repairs were performed in 184 (15.6%) underweight,
      640 (54.2%) normal-weight, 251 (21.3%) overweight, and 105 (8.9%) obese subjects
      (mean age 84.2 +/- 7.5; 80% female). Baseline American Society of
      Anesthesiologists (ASA) status was similar in all groups (ASA I/II vs III-V,
      P=.14). Underweight patients had a significantly higher risk of developing
      myocardial infarction (odds ratio (OR) 1.44, 95% confidence interval (CI)=1.0
      2.1; P=.05) and arrhythmias (OR=1.59, 95% CI=1.0-2.4; P=.04) than normal-weight
      patients. Multivariate analysis demonstrated that underweight patients had a
      higher risk of developing an adverse cardiac event of any type (OR=1.56, 95%
      CI=1.22-1.98; P<.001). Overweight and obese patients with hip fracture had no
      excess risk of any cardiac complication. CONCLUSION: The obesity paradox and low
      functional reserve in underweight patients may influence the development of
      postoperative cardiac events in elderly people with hip fracture.

PMID- 19175438
TI  - Healthcare costs associated with depression in medically Ill fee-for-service
      medicare participants.
AB  - OBJECTIVES: To examine the association between depression and healthcare costs in
      medically ill fee-for-service (FFS) Medicare recipients. STUDY DESIGN:
      Observational analysis of Medicare claims data. SETTING: Medicare Health Support
      (MHS) program at Green Ribbon Health. PARTICIPANTS: Fourteen thousand nine
      hundred two participants with diabetes mellitus, congestive heart failure (CHF),
      or both. MEASUREMENTS: This study examined participant data for a 12-month period
      before MHS enrollment (collected between November 2004 and August 2006). Twelve
      month healthcare costs (based on Medicare claims) in 2,108 participants with
      International Classification of Diseases, Ninth Revision, claims diagnoses of
      depression, 1,081 participants with possible depression (positive depression
      screen on the two-item Patient Health Questionnaire or self reported
      antidepressant use), and 11,713 participants without depression were compared.
      Gamma regression models were used to adjust for demographic and clinical
      differences and nonnormal distribution of cost data. RESULTS: Participants with
      depression had significantly higher total healthcare costs than those without
      ($20,046 vs $11,956; P<.01). Higher costs were observed in participants with
      depression in every cost category except specialty mental health care, which
      accounted for less than 1% of total healthcare costs. Participants with
      depression had higher costs in each quartile of increasing medical severity
      (measured using the Charlson Comorbidity Index). These differences remained
      statistically significant after adjusting for demographic and other clinical
      differences. CONCLUSION: Depression is associated with significantly higher
      healthcare costs in FFS Medicare recipients with diabetes mellitus and CHF. Only
      a small proportion of the increased costs are spent on mental health specialty
      care.

PMID- 19175437
TI  - A brief, intensive, clinically focused geriatrics course during the third year of
      medical school.
AB  - During the next several decades, the aging of the "baby boom" generation in the
      United States will result in a dramatic increase in the number of patients aged
      65 and older seeking medical care, but current projections suggest that the
      shortage of geriatrics-trained specialists will only worsen during this time
      period. As a result, the care of elderly patients will largely fall to other
      types of physicians. Consequently, it is imperative that medical school training
      include exposure to the basic skills needed to care safely for older adults. This
      goal is challenging, because the number of geriatric medicine faculty in most
      academic medical centers is small, and multiple other medical specialties are
      also vying for time in a busy medical school curriculum. Whether a 3-day course
      conducted during the third year of medical school could teach basic principles of
      geriatric medicine in a time- and manpower-effective manner was explored. It was
      found that even this brief exposure to geriatrics could have meaningful effects
      on student knowledge of and comfort with geriatrics.

PMID- 19175439
TI  - Which providers should communicate which critical information about a new
      medication? Patient, pharmacist, and physician perspectives.
AB  - OBJECTIVES: To investigate older patient, pharmacist, and physician perspectives
      about what information is essential to impart to patients receiving new
      medication prescriptions and who should provide the information. DESIGN:
      Qualitative focus group discussions. SETTINGS: Senior centers, retail pharmacies,
      and primary care physician offices. PARTICIPANTS: Forty-two patients aged 65 and
      older, 13 pharmacists, and 17 physicians participated in eight focus groups.
      MEASUREMENT: Qualitative analysis of transcribed focus group interviews and
      consensus through iterative review by multidisciplinary auditors. RESULTS:
      Patient, pharmacist, and physician groups all affirmed the importance of
      discussing medication directions and side effects and said that physicians should
      educate about side effects and that pharmacists could adequately counsel about
      certain important issues. However, there was substantial disagreement between
      groups about which provider could communicate which critical elements of
      medication-related information. Some pharmacists felt that they were best
      equipped to discuss medication-related issues but acknowledged that many patients
      want physicians to do this. Physicians tended to believe that they should provide
      most new-medication education for patients. Patients had mixed preferences.
      Patients aged 80 and older listed fewer critical topics of discussion than
      younger patients. CONCLUSION: Patients, pharmacists, and physicians have
      incongruent beliefs about who should provide essential medication-related
      information. Differing expectations could lead to overlapping, inefficient
      efforts that result in communication deficiencies when patients receive a new
      medication. Collaborative efforts to ensure that patients receive complete
      information about new medications could be explored.

PMID- 19175440
TI  - Level and change in cognitive test scores predict risk of first stroke.
AB  - OBJECTIVES: To determine whether cognitive test scores and cognitive decline
      predict incidence of first diagnosed stroke. DESIGN: Stroke-free Health and
      Retirement Study participants were followed on average 7.6 years for self- or
      proxy-reported first stroke (1,483 events). Predictors included baseline
      performance on a modified Telephone Interview for Cognitive Status (Mental
      Status) and Word Recall test and decline between baseline and second assessment
      in either measure. Hazard ratios (HRs) were estimated using Cox proportional
      hazards models for the whole sample and stratified according to five major
      cardiovascular risk factors. SETTING: National cohort study of
      noninstitutionalized adults with a mean baseline age of 64+/-9.9. PARTICIPANTS:
      Health and Retirement Study participants (n=19,699) aged 50 and older. RESULTS:
      Word Recall (HR for 1 standard deviation difference=0.92, 95% confidence interval
      (CI)=0.86-0.97)) and Mental Status (HR=0.89, 95% CI=0.84-0.95) predicted incident
      stroke. Mental Status predicted stroke risk in those with (HR=0.93, 95%=0.87
      0.99) and without (HR=0.81, 95% CI=0.72-.91) one or more vascular risk factors.
      Word Recall declines predicted a 16% elevation in subsequent stroke risk (95%
      CI=1.01-1.34). Declines in Mental Status predicted a 37% elevation in stroke risk
      (95% CI=1.11-1.70). CONCLUSION: Cognitive test scores predict future stroke risk,
      independent of other major vascular risk factors.

PMID- 19175441
TI  - A practice-based intervention to improve primary care for falls, urinary
      incontinence, and dementia.
AB  - OBJECTIVES: To determine whether a practice-based intervention can improve care
      for falls, urinary incontinence, and cognitive impairment. DESIGN: Controlled
      trial. SETTING: Two community medical groups. PARTICIPANTS: Community-dwelling
      patients (357 at intervention sites and 287 at control sites) aged 75 and older
      identified as having difficulty with falls, incontinence, or cognitive
      impairment. INTERVENTION: Intervention and control practices received condition
      case-finding, but only intervention practices received a multicomponent practice
      change intervention. MEASUREMENTS: Percentage of quality indicators satisfied
      measured using a 13-month medical record abstraction. RESULTS: Before the
      intervention, the quality of care was the same in intervention and control
      groups. Screening tripled the number of patients identified as needing care for
      falls, incontinence, or cognitive impairment. During the intervention, overall
      care for the three conditions was better in the intervention than the control
      group (41%, 95% confidence interval (CI)=35-46% vs 25%, 95% CI=20-30%, P<.001).
      Intervention group patients received better care for falls (44% vs 23%, P<.001)
      and incontinence (37% vs 22%, P<.001) but not for cognitive impairment (44% vs
      41%, P=.67) than control group patients. The intervention was more effective for
      conditions identified by screening than for conditions identified through usual
      care. CONCLUSION: A practice-based intervention integrated into usual clinical
      care can improve primary care for falls and urinary incontinence, although even
      with the intervention, less than half of the recommended care for these
      conditions was provided. More-intensive interventions, such as embedding
      intervention components into an electronic medical record, will be needed to
      adequately improve care for falls and incontinence.

PMID- 19175442
TI  - Strength and cost of an induced immune response are associated with a heritable
      melanin-based colour trait in female tawny owls.
AB  - 1. Melanin pigments provide the most widespread source of coloration in
      vertebrates, but the adaptive function of such traits remains poorly known. 2. In
      a wild population of tawny owls (Strix aluco), we investigated the relationships
      between plumage coloration, which varies continuously from dark to pale reddish,
      and the strength and cost of an induced immune response. 3. The degree of
      reddishness in tawny owl feather colour was positively correlated with the
      concentration of phaeomelanin and eumelanin pigments, and plumage coloration was
      highly heritable (h(2) = 0.93). No carotenoids were detected in the feathers. 4.
      In mothers, the degree of melanin-based coloration was associated with antibody
      production against a vaccine, with dark reddish females maintaining a stronger
      level of antibody for a longer period of time compared to pale reddish females,
      but at a cost in terms of greater loss of body mass. 5. A cross-fostering
      experiment showed that, independent of maternal coloration, foster chicks reared
      by vaccinated mothers were lighter than those reared by nonvaccinated mothers.
      Hence, even though dark reddish mothers suffered a stronger immune cost than pale
      reddish mothers, this asymmetric cost was not translated to offspring growth. 6.
      Our study suggests that different heritable melanin-based colorations are
      associated with alternative strategies to resist parasite attacks, with dark
      reddish individuals investing more resources towards the humoral immune response
      than lightly reddish conspecifics.

PMID- 19175443
TI  - Food web topology and parasites in the pelagic zone of a subarctic lake.
AB  - 1. Parasites permeate trophic webs with their often complex life cycles, but few
      studies have included parasitism in food web analyses. Here we provide a highly
      resolved food web from the pelagic zone of a subarctic lake and explore how the
      incorporation of parasites alters the topology of the web. 2. Parasites used
      hosts at all trophic levels and increased both food-chain lengths and the total
      number of trophic levels. Their inclusion in the network analyses more than
      doubled the number of links and resulted in an increase in important food-web
      characteristics such as linkage density and connectance. 3. More than half of the
      parasite taxa were trophically transmitted, exploiting hosts at multiple trophic
      levels and thus increasing the degree of omnivory in the trophic web. 4. For
      trophically transmitted parasites, the number of parasite-host links exhibited a
      positive correlation with the linkage density of the host species, whereas no
      such relationship was seen for nontrophically transmitted parasites. Our findings
      suggest that the linkage density of free-living species affects their exposure to
      trophically transmitted parasites, which may be more likely to adopt highly
      connected species as hosts during the evolution of complex life cycles. 5. The
      study supports a prominent role for parasites in ecological networks and
      demonstrates that their incorporation may substantially alter considerations of
      food-web structure and functioning.

PMID- 19175444
TI  - Body size and predatory performance in wolves: is bigger better?
AB  - 1. Large body size hinders locomotor performance in ways that may lead to trade
      offs in predator foraging ability that limit the net predatory benefit of larger
      size. For example, size-related improvements in handling prey may come at the
      expense of pursuing prey and thus negate any enhancement in overall predatory
      performance due to increasing size. 2. This hypothesis was tested with
      longitudinal data from repeated observations of 94 individually known wolves
      (Canis lupus) hunting elk (Cervus elaphus) in Yellowstone National Park, USA.
      Wolf size was estimated from an individually based sex-specific growth model
      derived from body mass measurements of 304 wolves. 3. Larger size granted
      individual wolves a net predatory advantage despite substantial variation in its
      effect on the performance of different predatory tasks; larger size improved
      performance of a strength-related task (grappling and subduing elk) but failed to
      improve performance of a locomotor-related task (selecting an elk from a group)
      for wolves > 39 kg. 4. Sexual dimorphism in wolf size also explained why males
      outperformed females in each of the three tasks considered (attacking, selecting,
      and killing). 5. These findings support the generalization that bigger predators
      are overall better hunters, but they also indicate that increasing size
      ultimately limits elements of predatory behaviour that require superior locomotor
      performance. We argue that this could potentially narrow the dietary niche of
      larger carnivores as well as limit the evolution of larger size if prey are
      substantially more difficult to pursue than to handle.

PMID- 19175445
TI  - Interactions to the fifth trophic level: secondary and tertiary parasitoid wasps
      show extraordinary efficiency in utilizing host resources.
AB  - 1. Parasitoid wasps are highly efficient organisms at utilizing and assimilating
      limited resources from their hosts. This study explores interactions over three
      trophic levels, from the third (primary parasitoid) to the fourth (secondary
      parasitoid) and terminating in the fifth (tertiary parasitoid). 2. Host
      utilization and adult body mass of the secondary and tertiary parasitoid Gelis
      agilis was determined when developing on pre-pupae of its primary parasitoid
      host, Cotesia glomerata, and from pre-pupae of another secondary parasitoid,
      Lysibia nana that had developed initially on pre-pupae of C. glomerata. 3. In
      both C. glomerata and G. agilis, the body mass of emerging adult parasitoids was
      strongly positively correlated with initial cocoon mass. For a given cocoon mass
      at parasitism, emerging adult G. agilis wasps were almost 90% as large as C.
      glomerata adults developing in healthy cocoons of comparable mass. Furthermore,
      G. agilis adults were still 75% as large as C. glomerata adults even when
      developing on L. nana that in turn had developed on C. glomerata. Otherwise, in
      terms of adult body mass per unit of host resources, there was no apparent
      difference in the quality of C. glomerata or L. nana hosts for the development of
      G. agilis. 4. Analyses of carbon and nitrogen in body tissues of the parasitoids
      over the third to the fifth trophic level revealed that percentage nitrogen was
      higher and carbon lower in G. agilis and L. nana than in C. glomerata.
      Furthermore, percentage carbon was lower in adult G. agilis wasps that had
      developed from L. nana than from C. glomerata. 5. We argue that the remarkable
      efficiency which characterizes the development of secondary and tertiary
      parasitoids is based on the very high nutritional quality of resources that
      increase in quality up the food chain and rigid selection optimizing allocation
      of limited host resources. Consequently, food webs involving secondary and
      tertiary parasitoids can go to levels hitherto unexplored thus far in empirical
      studies. The use of molecular markers in future studies may reveal just how long
      food chains involving these insects may extend.

PMID- 19175446
TI  - Parasite intensity and fur coloration in reindeer calves - contrasting artificial
      and natural selection.
AB  - 1. In reindeer, the variation in fur coloration is higher in semi-domesticated
      than in wild populations. This difference might result from impacts of natural
      enemies acting on conspicuously coloured individuals with higher intensity in
      natural than semi-domesticated populations. 2. While predator pressure is rather
      similar for wild and semi-domesticated populations, semi-domesticated reindeer
      are less impacted by parasitism due to endectocidic treatment. In this study, we
      estimated the intensity of warble flies in different reindeer colour morphs in a
      large sample of untreated calves from multiple semi-domesticated herds in
      northern Norway. 3. We found that lighter coloured reindeer calves have higher
      intensities of warble fly larvae than darker ones. This is associated with a
      decrease in body mass, and may hence influence subsequent fitness of the animals.
      4. The high intensity of parasites in white calves implies that they are either
      more exposed or less resistant to parasitic infections. In either case,
      parasitism by warble flies appears to be a proximate cause driving coloration of
      reindeer towards a reduced variability in natural populations.

PMID- 19175447
TI  - Anodal capture, cathodal capture, and left ventricular cardiac excitation.

PMID- 19175448
TI  - The work-up and management of patients with apparent or subclinical cardiac
      sarcoidosis: with emphasis on the associated heart rhythm abnormalities.
AB  - In patients with newly diagnosed AV block and/or ventricular tachycardia, cardiac
      sarcoidosis should always be considered in the differential diagnosis. In
      addition to the pacemaker implant, cardiac resynchronization therapy (CRT) should
      be selected for severe heart failure patients who have class III or IV heart
      failure, LVEF <or=35%, and a complete LBBB pattern. If the disease activity is
      high, corticosteroid therapy is recommended. Patients with extracardiac
      sarcoidosis need to be closely followed for potential cardiac involvement, as the
      mortality in sarcoidosis depends on cardiac involvement. Early diagnosis and
      treatment of cardiac sarcoidosis is essential. Positron emission tomography (PET)
      and cardiac magnetic resonance imaging (MRI) are considered to have high
      sensitivity for cardiac involvement, and are the preferred imaging modalities.
      However, even in the era of new technology, such as PET and cardiac MRI, early
      diagnosis of cardiac sarcoidosis is still difficult.

PMID- 19175449
TI  - Initial clinical experience with the new irrigated tip magnetic catheter for
      ablation of scar-related sustained ventricular tachycardia: a small case series.
AB  - BACKGROUND: A remote magnetic navigation system (MNS) has been used with a
      nonirrigated magnetic catheter for ablation of some supraventricular and
      ventricular arrhythmias. However, the irrigated tip catheter has not been
      evaluated. OBJECTIVE: To evaluate the feasibility and efficiency of the newly
      available irrigated tip magnetic catheter for radiofrequency ablation (RF) of
      electrical storm due to scar-related ventricular tachycardia (VT) in patients
      with ischemic heart disease. METHODS: Between January and March 2008, a total of
      4 consecutive patients (4 men, mean age 67.7 years) with electrical storm who had
      an implantable cardioverter defibrillator underwent radiofrequency ablation using
      a remote MNS and the new magnetic irrigated catheter. RESULTS: Five ablation
      procedures were performed in study patients. Acute success, defined as
      noninducibility of any monomorphic VT, was obtained in 3 patients. In 1 patient,
      a nonclinical VT remained inducible. A monomorphic VT corresponding to clinical
      VT with the median (range) cycle length of 485 (440-580) ms was induced in all
      patients. The duration of ablation was 2,273 (985-3087) seconds, with median
      total procedure and fluoroscopy times of 135 (100-150) minutes and 6.5 (5-9)
      minutes, respectively. One recurrence occurred 1 week after ablation, which was
      ablated successfully in the second session. No complication was observed after
      ablation. During mean follow-up of 4.2 months, all patients were in sinus rhythm,
      they received no ICD therapy, and no mortality occurred. CONCLUSIONS: Irrigated
      ablation of scar-related ventricular tachycardia guided by remote MNS is a
      feasible and effective modality for management of the electrical storm in
      patients with ischemic cardiomyopathy with minimal radiation exposure.

PMID- 19175450
TI  - Avoid delivering therapies for nonsustained fast ventricular tachyarrhythmia in
      patients with implantable cardioverter/defibrillator: the ADVANCE III Trial.
AB  - INTRODUCTION: The purpose of this investigation is to evaluate whether a
      prolonged detection interval for life threatening ventricular tachyarrhythmia
      (VT) is able to reduce therapies (Rx) delivered by an implantable
      cardioverter/defibrillator (ICD). Until now, only the PREPARE trial demonstrated
      a reduction of ICD Rx in a cohort of primary prevention patients. METHODS AND
      RESULTS: The ADVANCE III study is a prospective, randomized, parallel trial with
      2 arms evaluating different intervals to detect (NID), i.e., 18/24 (as currently
      used) versus 30/40. The primary endpoint is to demonstrate a 20% reduction of ICD
      Rx (antitachycardia pacing or shocks) delivered to terminate spontaneous VT with
      a cycle length < or =320 ms in patients with Class I-IIA indication for ICD
      therapy, regardless of cardiac resynchronization capabilities. The worldwide
      investigation started in spring 2008 and is expected to be finished in 2011.
      CONCLUSIONS: The ADVANCE III trial is the first randomized investigation
      evaluating the reduction of ICD Rx for fast VT due to a prolongation of NID in a
      general ICD patient cohort.

PMID- 19175451
TI  - Ruminal fermentation, microbial growth and amino acid flow in single-flow
      continuous culture fermenters fed a diet containing olive leaves.
AB  - Six single-flow continuous culture fermenters were used to determine fermentation
      profile, microbial growth and amino acid (AA) flow promoted by olive leaves
      supplemented with barley grains and faba beans (OLSUP), and alfalfa hay (AH). Two
      incubation runs were carried out with three fermenters inoculated with ruminal
      fluid from wethers and three from goats. The inoculum source did not affect (p =
      0.059 to 0.980) any of the parameters. Daily volatile fatty acid (VFA) production
      and carbohydrate digestibility were greater (p = 0.009 and 0.024, respectively)
      for AH, therefore the pH values were lower (p = 0.015) than for OLSUP. Acetate
      was greater (p < 0.001) and isobutyrate, isovalerate and caproate lower (p <
      0.001 to 0.006) for AH with greater acetate/propionate (p = 0.014) and
      'VFA/digested carbohydrate' (p = 0.026) ratios. Daily microbial N flow and
      efficiency were greater (p = 0.016 and p = 0.041) for diet AH. Individual AA
      flows were greater (p < 0.001 to 0.016) for AH, but microbial essential AA
      proportion was greater for OLSUP (p = 0.015). The results indicate that OLSUP
      promoted lower bacterial growth and AA flow than AH, which could have been
      partially due to a limitation of N availability to ruminal microbes.

PMID- 19175452
TI  - Dietary amylose and amylopectin ratio and resistant starch content affects plasma
      glucose, lactic acid, hormone levels and protein synthesis in splanchnic tissues.
AB  - Experiments were conducted to determine the effects of feeding different starch
      sources on piglets. Four diets were formulated with maize, brown rice, sticky
      rice and Hi-Maize 1043 as starch sources, with resistant starch (RS) contents of
      2.3%, 0.9%, 0.0%, 20.6%, and amylose and amylopectin ratio of 0.23%, 0.21%,
      0.18%, 0.06% respectively. Fifty-six pigs weaned at 28 days of age were randomly
      assigned to one of the four diets. In Exp. 1, six piglets in each group were
      fitted with an indwelling jugular catheter. After 25 days of feeding trial,
      venous blood samples were obtained at time zero and every 1 h for 4 h. In Exp. 2,
      the remaining piglets were used to determine the effects of different starch
      sources on the fractional synthesis rate (FSR). The results indicated that
      feeding the Hi-Maize 1043 diet decreased (p < 0.05) plasma contents of glucose,
      insulin, lactic acid and T(3), while sticky rice increased plasma contents of
      glucose and insulin. The insulin contents in piglets fed the sticky rice diet was
      69.2 microIU/ml at 1 h post-feeding which was highest among the starch diets. The
      FSR in the pancreas, spleen, duodenum, jejunum, ileum and colon in the corn group
      were much higher (p < 0.05) than that in the sticky rice group. These results
      suggest that RS is potentially beneficial for improving insulin sensitivity in
      young pigs and that the ratio of amylose and amylopectin have significantly
      effects on the FSR in splanchnic tissues in weaned piglets. Another finding of
      this study indicated maize with a ratio of amylose and amylopectin of 0.23 has
      the best starch sources for pig production.

PMID- 19175454
TI  - Sunflower oil supplementation alters meat quality but not performance of growing
      partridges (Alectoris chukar).
AB  - This study was conducted to evaluate the effects of sunflower oil supplementation
      (0%, 3%, 6% and 9%) to partridge chicks (Alectoris chukar) on growth performance,
      nutrient digestibility and carcass characteristics. Feed consumption and live
      weight gain were responsive to dietary sunflower oil inclusion during the starter
      period, but not during the grower period. Increasing sunflower oil level linearly
      increased crude protein and fat digestibilities. Except for abdominal fat,
      weights of inedible parts and edible organs remained unchanged by the diets. The
      treatments linearly decreased weight and efficiency of carcass and weights of
      wings and breast and did not alter weights of thighs and neck. Breast meat
      saturated fatty acids decreased linearly by 17.9% and unsaturated fatty acids
      increased linearly by 10.6%, as sunflower oil level increased in the diets.
      Monounsaturated fatty acids decreased linearly by 27.3%, whereas polyunsaturated
      fatty acids increased linearly by 51%. Overall, n-3 (0.78% vs. 0.59%) and n-6
      (42.6% vs. 29.8%) were greater in breast meat in treatment groups than in control
      group. In conclusion, sunflower addition into diets has minimal effects on
      performance of growing partridges, but significantly alters meat fatty acid
      composition.

PMID- 19175453
TI  - Effects of carbohydrate sources on growth, body composition and tissue lipid
      deposition of blackspot seabream, Pagellus bogaraveo (Brunnich).
AB  - Rearing blackspot seabream has been associated with low growth rates and
      excessive lipid accumulation, resulting in a reduction of the edible yield. The
      effect of extruded diets containing different carbohydrate sources (wheat vs.
      wheat bran) was evaluated on 100 g blackspot seabream growth performance, feed
      utilization and fat deposition, taking into consideration the optimal dietary
      protein and lipid level described for smaller-sized fish. A fish meal-based diet
      was also tested as a control to assure maximal growth rates were achieved. The
      experiment was held in sea cages at environmental conditions. Duplicate groups of
      fish were distributed among six cages with a stocking density of 1.3 kg/m(3) and
      hand-fed each diet for 7 months. At the end of the experiment, fish in all groups
      doubled their body weight attaining 190-230 g. Specific growth rate (0.3-04),
      feed conversion ratio (1.3-1.6) and protein gain (0.5-0.6 g/kg/day) were similar
      among treatments. The Hepatosomatic Index, the Viscerosomatic Index and final
      whole body composition did not vary significantly among dietary treatments;
      nevertheless, the inclusion of wheat bran induced a significant increase of liver
      lipid content and the highest mesenteric fat index. All diets were effective in
      reducing whole body and mesenteric fat compared with initial values.

PMID- 19175455
TI  - Long-term feeding effects of dietary protein levels on egg production,
      immunocompetence and plasma amino acids of laying hens in subtropical condition.
AB  - The objective of this study was to determine the effect of protein levels on
      production performance, immune response, liver triglyceride and plasma amino
      acids profile of laying hens during 21-48 weeks of age. Two groups of commercial
      hens (Babcock B-308) were fed with diets with different crude protein levels (14%
      and 18% CP). The high protein diet (18% CP) significantly increased production
      performance, essential amino acid intake, spleen weight (% of body weight), ND
      titre (haemagglutination-inhibition test), serum albumin (g/dl), serum alpha
      globulin and plasma essential amino acids (except histidine) and decreased liver
      triglyceride (mg/g liver) in relation to the low protein diet (14% CP). In long
      term effect, therefore, this study suggested that adequate dietary condition of
      amino acids, particularly methionine and branch-chain amino acids is necessary
      for sustaining normal immunocompetence and achieving maximum production
      performance.

PMID- 19175456
TI  - The effect of weight loss on protein profiles of gastrocnemius muscle in rabbits:
      a study using 1D electrophoresis and peptide mass fingerprinting.
AB  - The study of physiological changes occurring during selection contributes to an
      improved understanding of relationships leading to efficiencies in animal
      production. To investigate the effects of food restriction in gastrocnemius
      muscle protein expression, 20% weight reduction was induced in New Zealand White
      (meat producing) and wild rabbits, using one-dimensional gel electrophoresis and
      peptide mass fingerprinting. Lower expression levels of myosin heavy chains were
      found in the Wild Rabbits Restricted Group, while myosin light chain and alpha
      crystallin proteins were not detected in restricted groups. Glyceraldeyde-3
      phosphate dehydrogenase and glycogen phosphorylase expression levels were similar
      for all experimental groups. Phosphopyruvate hydratase beta was not detected in
      the wild rabbit restricted diet group. Pyruvate kinase levels were 50% lower in
      the New Zealand Restricted group. LIM protein detection was absent in the control
      New Zealand group. Results also show relevance of actin in preserving muscle
      structure in depressed food availability, the sensitivity of both myosin light
      chain and alpha-crystallin protein to restricted feed and the role of PK in the
      resistance of New Zealand rabbits to food restriction.

PMID- 19175457
TI  - Effect of induced body condition score differences on physiological response,
      productive and reproductive performance of Malpura ewes kept in a hot, semi-arid
      environment.
AB  - This study was undertaken to study the influence of induced body condition score
      (BCS) differences on physiological response, productive and reproductive
      performance of Malpura ewes to optimise BCS for these ewes for maximising
      production making it economically viable. The study was conducted for a period of
      1 year using thirty healthy Malpura ewes (2-4 year old). The animals were
      randomly divided and different BCS was induced within three groups named Group I
      (BCS 2.5; n = 10), Group II (BCS 3.0-3.5; n = 10) and Group III (BCS 4.0; n =
      10). The parameters included in the study were allometric measurements,
      physiological response, wool yield and reproductive performance. BCS had a
      significant influence on allometric measurements, respiration rate and different
      reproductive parameters studied, while wool production differed significantly
      during spring and non-significantly during autumn. The results revealed that the
      reproductive performance of Malpura ewes with a BCS of 3.0-3.5 was better in
      comparison with the groups with lower and higher BCS. It may be concluded from
      this study that an active management of breeding sheep flock to achieve a BCS of
      3.0-3.5 may prove to result in an economically viable return from these flocks.

PMID- 19175458
TI  - Inter- and intra-individual differences in serum copper and zinc concentrations
      after feeding different amounts of copper and zinc over two lactations.
AB  - The influence of different copper and zinc contents in rations on blood serum
      concentrations was tested in a feeding trial at the Institute of Animal Nutrition
      of the Federal Research Institute for Animal Health (FLI). A total of 60 German
      Holstein breed cows (38 first lactating and 22 second lactating cows) were
      tested. All animals received a diet based on maize- and grass silage ad libitum.
      The animals were divided into two groups with 30 cows each. Group A received
      concentrates supplemented with copper and zinc as recommended, whereas Group B
      was offered a concentrate with roughly double the amount of copper and zinc.
      Blood samples were taken several times during the lactation. The concentrations
      of copper and zinc in the serum were measured and correlations between trace
      element intake and their serum concentrations were calculated. The mean dry
      matter intake was significantly higher for cows in the second lactation (19.1
      kg/day) than for cows in the first lactation (16.4 kg/day), whereas the DM-intake
      was constant in the different feeding groups (17.3 and 17.4 kg/day). The
      correlation between feed intake in the first and the second lactation was r =
      0.76. The copper concentration in the serum was not influenced by the different
      feedings (11.9 and 12.5 micromol/l), but high variations were found between the
      cows. The influence of the lactation number was not significant (12.1 and 12.4
      micromol/l). In contrast to copper, the zinc concentration in the serum was
      significantly higher for Group B (14.0 micromol/l) than for Group A (12.2
      micromol/l), respectively, for second lactating cows (13.8 micromol/l) in
      relation to 12.7 micromol/l for first lactating cows. The individual variation
      was also high as for copper. Neither the correlation between copper intake and
      copper serum concentration nor the correlation between zinc intake and zinc serum
      concentration was significant.

PMID- 19175459
TI  - Effects of dietary additives (potassium diformate/organic acids) as well as
      influences of grinding intensity (coarse/fine) of diets for weaned piglets
      experimentally infected with Salmonella Derby or Escherichia coli.
AB  - The aim of this study was to examine whether and to what extent the addition of
      potassium diformate (pdf) or free organic acids (fpa) to the diet and the
      grinding intensity might affect the course of infection and the passage of orally
      applied Salmonella and Escherichia coli in pigs. Experiments were carried out
      using 80 reared piglets allotted to four groups. Pigs were fed pelleted diets ad
      libitum (except during a 15 h feed-withholding-period before infection). The
      control diet contained finely ground cereals (2 mm screen). To two test diets
      (also finely ground) 1.2% pdf, 0.9% organic acids (75% formic and 25% propionic
      acid, fpa) respectively were added. The fourth diet (without acids) was based on
      coarsely ground cereals (6-mm screen). After experimental infection alternately
      with S. Derby or E. coli, the course of infection was examined (rectal swab
      technique). Pigs were sacrificed 4-5 h after a further oral application of
      approximately 10(9)-10(10) CFU S. Derby or E. coli to determine the counts of
      Salmonella or E. coli in chyme (classical culture methods). Adding pdf or fpa to
      the diet led to reduced Salmonella shedding and resulted in significantly lower
      counts of Salmonella and E. coli in the stomach content indicating an improved
      efficacy of the stomach barrier. In the distal parts of the digestive tract, the
      effect was less obvious concerning counts of E. coli, whereas counts of
      Salmonella were reduced markedly as well. The diet based on coarsely ground
      cereals failed to demonstrate positive effects concerning infection and passage
      of orally applied bacteria as well, but this diet was also pelleted and showed
      unintentionally, comparable amounts of fine particles. Results obtained in this
      study allow the recommendation of using pdf or organic acids as additives when
      dietary measures against Salmonella or E. coli in pigs are required.

PMID- 19175460
TI  - Microhandling of vesicular glutamate uptake modulate feeding in broilers.
AB  - Glutamate (Glu), the major excitatory neurotransmitter in vertebrate central
      nervous system, is actively taken up and stored in synaptic vesicles. On the
      arrival of an action potential to the pre-synaptic membrane and the subsequent
      opening of the voltage-gated calcium channels and movement of Ca(2+) into the
      neuron, these small vesicles fuse with the pre-synaptic membrane to release the
      neurotransmitter content into the synaptic cleft. Because it has previously been
      shown that intracerebroventricular (ICV) glutamate plays a role in feed intake in
      broilers, the manipulation of its vesicular concentration could affect feeding
      behaviour. On the contrary, research on vesicular glutamate transporters has, so
      far, been carried out on mammalian species. In the present study, we aim to
      examine the effect of Chicago sky blue 6B (CSB6B), a glutamate vesicular uptake
      inhibitor, on feed intake and latency to start feeding in a commercial strain of
      meat type chickens. To do this, four experiments have been designed to
      investigate the effect of ICV injection of saline, glutamate, as a general
      agonist for glutamate receptors, CSB6B and the combination of Glu and CSB6B. The
      findings indicate that CSB6B increases feed intake and decreases the latency to
      start feeding in 24-h-feed-deprived Ross 208 broilers.

PMID- 19175461
TI  - Effects of humic substances supplementation provided through drinking water on
      performance, carcass traits and meat quality of broilers.
AB  - The present study aimed at evaluating the effects of different doses of humic
      substances (HS) in waterer pan on broiler performances and meat quality. For the
      trial, 480 chicks (ROSS 308) were allocated into four groups (HS0, HS150, HS300
      and HS450) of 120 equally mixed-sex birds, each receiving a drinking water
      supplemented with 0, 150, 300 and 450 ppm of a humic acid (provided by 0.0%,
      0.5%, 1.0% and 1.5% of HS, v/v) respectively. At the age of 21 and 42 days, feed
      consumption and live weight were taken. At the age of 42 days, 16 birds per
      treatment were slaughtered, dressing percentages, digestive tract traits were
      evaluated and samples of breast (pectoralis major) and thigh (iliotibialis) meat
      were taken to evaluate the changes in colour characteristics (CIE L*, a* and b*)
      and chemical composition. The body weight gain increased by the HS300 in relation
      to the HS0 and HS450, and decreased by the HS450 in relation to the HS0. The feed
      consumption of birds in the HS450 and feed efficiency of birds in the HS300 were
      lower and higher than those in the other treatments respectively. The carcass
      weight of broilers in the HS150 and HS300 were higher than those of in the HS0
      and HS450. The carcass weight decreased by the HS450 in relation to the other
      treatments. The dressing percentage increased by the HS150 in relation to the
      HS450. The HS450 resulted in breast and thigh meat colour that were lighter than
      those found in the HS0 birds. The HS450 increased fat content of thigh meat in
      relation to the HS0. It was concluded that the humic acid supplementation at 300
      ppm and 450 ppm appears to have a measurable impact on live performance improving
      feed efficiency and lightness of breast and thigh meat colours in broilers
      respectively.

PMID- 19175462
TI  - Growth performance and puberty attainment in growing pigs fed dietary fumonisin
      B(1).
AB  - Twenty-four male weaned piglets assigned to four diets containing 5.0, 10.0, 15.0
      and 0.2 mg fumonisin B(1) (FB(1)) /kg as diets 1, 2, 3 and control diet,
      respectively, were used to study the effect of dietary FB(1) on growth and
      puberty attainment in pigs in a 6-month feeding trial. Lower feed intake during 0
      4 months and a non-significant (p > 0.05) but FB(1) concentration-dependent
      decrease in live and DWGs in animals fed FB(1)-contaminated diets was observed at
      the end of the pubertal phase. The daily and the final live weight gains of
      animals fed diet 3 were 75.8% and 90.6%, respectively, of the control values. The
      mean ages at puberty by boars on diets 2 and 3 were significantly (p < 0.05)
      higher than those for animals on the control and diet 1. The animals on diet 3
      attained puberty when mean live weight was 60.1 kg, some 30.3 days after the
      controls attained puberty, at 156.3 days, when the mean live weight was 46.9 kg.
      This study revealed that dietary FB(1) delays sexual maturity in growing pigs.
      Male weanling pigs for breeding should not be exposed to dietary FB(1) higher
      than 5 mg/kg for optimum growth and reproductive performance.

PMID- 19175463
TI  - Mineral absorption in tapirs (Tapirus spp.) as compared to the domestic horse.
AB  - To test whether mineral recommendations for horses are likely to guarantee
      adequate mineral provision for tapirs (Tapirus spp.), we investigated the
      apparent absorption (aA) of macro and micro-minerals in 18 tapirs from five
      zoological institutions in a total of 24 feeding trials with total faecal
      collection. Samples of feeds and faeces were analysed for Ca, P, Mg, Na, K, Fe,
      Cu and Zn. The resulting aA coefficients and the linear relationships of
      apparently absorbable dietary mineral content to total dietary mineral content
      (per 100 g dry matter) were compared with data for domestic horses. While there
      were no apparent differences in the absorption patterns for P, K, Na, Fe, Cu or
      Zn, the absorption of both Ca and Mg was distinctively higher in tapirs than in
      horses. Tapirs are browsers that are adapted to a diet of higher Ca content and
      higher Ca:P ratio than equids, and high absorptive efficiency for Ca might have
      evolved to ensure that high dietary Ca concentrations do not lead to the binding
      of dietary P in the intestine, making it unavailable for hindgut microbes.
      Similar to other hindgut fermenters, in tapirs, absorption coefficients for Ca
      increased with dietary Ca:P ratio, and urinary Ca:creatinine ratios increased
      with dietary Ca. Several zoo diets used were deficient in one or more minerals.
      When compared with faeces of free-ranging animals, faeces of zoo animals had
      higher concentrations of most minerals, probably indicating a lesser diluting
      effect of indigestible fibre in zoo animals.

PMID- 19175464
TI  - Effect of soybean peptides on growth performance, intestinal structure and
      mucosal immunity of broilers.
AB  - Five-hundred 1-day-old broilers were randomly assigned to five groups, 100
      chickens for each group. From group 1 to 3, 80, 120 and 200 mg/kg soybean
      peptides was added to the diets respectively; in the fourth group, 3.2 mg/kg
      genramycin was added; and the fifth group was the control without soybean
      peptides and antibiotics. At the age of 28 and 49 days, the number of goblet
      cells (GC), intestine intraepithelial lymphocyte, immunoglobulin A-forming cells,
      the ratio of villous height and crypt depth (V/C) of broiler's duodenum, jejunum
      and cecum were observed by the application of haematoxylin and eosin or
      histochemistry staining. The results indicated that soybean peptides added with
      80-120 mg/kg could increase daily weight gain, the number of GC and V/C. Soybean
      peptides could modulate intestinal mucosal immunity of broilers.

PMID- 19175475
TI  - Bullous-vesicular variant of mycosis fungoides presenting as erythema annulare
      centrifugum: a case report.

PMID- 19175465
TI  - Oncogenesis and cancer stem cells: current opinions and future directions.
AB  - There is increasing evidence to show that only a subset of cancer cells drives
      the growth and progression of a tumour. These cells share similar properties with
      normal stem cells and are termed 'cancer stem cells'. Cancer stem cells have been
      identified in acute myeloid leukaemia and in some solid tumours by their distinct
      expression of cell surface antigens. Their long-term, self-renewing capacity is
      thought to be a determining factor in the maintenance and regrowth of the tumour.
      Studies on haematopoietic cancers show that important signalling pathways and
      genes for normal haematopoiesis, such as Wnt, NF-kappaB, Notch, hedgehog (Hh) and
      Bmi1, are oncogenic, thereby potentially involved in cancer stem cell regulation.
      Elimination of cancer stem cells in tumours could result in the degeneration of
      downstream cells, which makes them potential targets for new cancer therapies.

PMID- 19175476
TI  - Clopidogrel-induced fixed drug eruption.

PMID- 19175477
TI  - Reconstruction of human dermal papilla-like tissue in vitro.

PMID- 19175478
TI  - Erythermalgia revealing two aetiologies: polycythemia vera and a cervical rib.

PMID- 19175479
TI  - Acute generalized exanthematous pustulosis caused by varenicline.

PMID- 19175480
TI  - Occurrence of poroid hidradenomas after haematopoietic stem cell transplantation.

PMID- 19175481
TI  - Kobner phenomenon in psoriasis induced by Mantoux test.

PMID- 19175482
TI  - Median canaliform dystrophy of Heller with associated swan neck deformity.

PMID- 19175483
TI  - Complete loss of epithelial antigens in a recurrent tumour from squamous cell
      carcinoma of the scalp.

PMID- 19175484
TI  - Familial longitudinal melanonychia and premature hair greying: a new genetic
      entity?

PMID- 19175485
TI  - Halo naevus is associated with leucotrichia: use of portable digital microscopy.

PMID- 19175486
TI  - Successful association in the treatment of pityriasis lichenoides et
      varioliformis acuta.

PMID- 19175487
TI  - Presumptive frequency of, and review of reports on, allergies to  household
      gloves.
AB  - BACKGROUND: Allergies to latex or 'rubber chemicals' in medical or other
      occupationally used gloves are not uncommon. In contrast, very few articles have
      reported on latex allergy (type I) or allergic contact sensitization to additives
      (type IV) associated with household gloves, in spite of some 44 million pairs
      sold in Germany in, e.g., 2006. OBJECTIVE: We seek to determine the frequency of
      allergies to household gloves by providing own data and we reviewed the
      literature. METHODS: The study was based on 105083 consultations of patients with
      suspected contact allergy (Type IV) in the Information Network of Departments of
      Dermatology (IVDK) in Germany in the years 1995 to 2006 and on the PubMed
      databases (last access 7/2008). RESULTS: 1221 patients were identified in whom
      protective gloves were considered as a possible cause of contact dermatitis and
      who did not work in occupations associated with above average risk of contact
      allergy to rubber chemicals. In 178 cases positive reactions to rubber components
      were reported, while 13 additional cases reacted only to a previously used rubber
      glove brand, but not to commercial allergens. In the literature only two
      publications on type I and two on type IV reactions were found in which allergies
      to rubber household gloves were explicitly reported. CONCLUSIONS: Allergies to
      rubber household gloves seem to be rare. Factors presumably counteracting contact
      sensitization by household gloves, compared to occupational use, comprise short
      intermediate use, loose fitting and the incorporation of e.g. an inner cotton
      surface reducing skin contact with rubber chemicals.

PMID- 19175488
TI  - A survey of the quality and accuracy of information leaflets about skin cancer
      and sun-protective behaviour available from UK general practices and community
      pharmacies.
AB  - BACKGROUND: Better information promotes sun protection behaviour and is
      associated with earlier presentation and survival for malignant melanoma. Aim To
      assess the quality of patient information leaflets about skin cancer and sun
      protective behaviour available from general practices and community pharmacies.
      DESIGN OF STUDY: A structured review of patient information leaflets. Setting All
      community pharmacies and general practices in one Primary Care Trust were invited
      to supply leaflets. METHODS: Readability was assessed using the SMOG scoring
      system. Presentation and content were reviewed using the Ensuring Quality
      Information for Patients (EQIP) guidelines. Three consultant dermatologists
      assessed each leaflet for accuracy. RESULTS: Thirty-one different patient
      information leaflets were returned. Thirteen (42%) were published in the previous
      2 years, but 10 (32%) were over 5 years old. Nine (29%) leaflets were produced by
      the NHS or Health Education Authority, and 8 (27%) were linked to a commercial
      organization. One leaflet had readability in the primary education range (SMOG
      score = 6), and none with the recommended range for health education material
      (SMOG score < or = 5). Two leaflets (6%) were in the highest quartile of EQIP
      score for presentation and content. Five leaflets (17%) had a major inaccuracy
      such as over-reliance on sun screen products instead of shade and clothing.
      CONCLUSIONS: Leaflets were of variable quality in presentation and content. All
      required a reading age higher than recommended. All leaflets with major
      inaccuracies had links with commercial organizations. This study raises important
      issues about the potential conflict between marketing and health messages in the
      way sun creams are promoted.

PMID- 19175489
TI  - Exploring issues influencing the use of the Malnutrition Universal Screening Tool
      by nurses in two Australian hospitals.
AB  - BACKGROUND: Nutrition screening using evidence-based clinical practice is
      important for identifying patients whose nutritional status may be compromised,
      so that they receive appropriate treatment. Introduction of the Malnutrition
      Universal Screening Tool ('MUST') in two wards in two Melbourne hospitals
      resulted in low screening completion rates by nursing staff. Nurses' screening
      practices were explored to understand personal and workplace barriers to
      compliance. METHODS: Surveys of patients' medical records and focus groups with
      nurses were used to gather data. Audio-recorded group narratives were transcribed
      verbatim, and then coded thematically to develop understandings of response
      patterns. RESULTS: A survey of admitted patients (n = 46) showed low screening
      rates by ward (17% and 62%). Eighteen nurses in two wards participated in three
      focus groups. The five main themes that emerged were: 'screening role', 'task
      priorities', 'recognition of evidence-based practice', 'uncertainty of protocols'
      and 'degree of competence'. Screening completion was limited by workloads,
      uncertainty about screening policy and also individuals' skill in use of the
      tool. CONCLUSIONS: Application of 'MUST' can be facilitated by increasing nurses'
      competence through training and by the provision of ongoing support. When
      implementing nutrition risk screening, dietitians' roles should include
      continually working with nurses to identify and reduce the barriers that prevent
      the adoption of universal screening. Enhancement of collaboration is essential to
      ensure that optimal nutrition care occurs.

PMID- 19175490
TI  - Association between folate, vitamin B(6) and vitamin B(12) intake and depression
      in the SUN cohort study.
AB  - BACKGROUND: An association between low blood levels of folate, vitamins B(6) and
      B(12) and a higher prevalence of depressive symptoms has been reported in several
      epidemiological studies. The present study aimed to assess the association
      between folate, vitamins B(6) and B(12) intake and depresion prevalence in the
      SUN cohort study. METHODS: The study comprised a cross-sectional analysis of 9670
      participants. A validated semi-quantitative food frequency questionnaire was used
      to ascertain vitamin intake. The association between the baseline intake of
      folate, vitamins B(6) and B(12) categorised in quintiles and the prevalence of
      depression was assessed. The analyses were repeated after stratifying by smoking
      habits, alcohol intake, physical activity and personality traits. RESULTS: Among
      women, odds ratios (OR) [95% confidence interval (CI)] for the third to fifth
      quintile for vitamin B(12) intake were 0.58 (0.41-0.84), 0.56 (0.38-0.82) and
      0.68 (0.45-1.04), respectively. Among those men with a low level of anxiety and
      current smokers, a significant positive association between low folate intake and
      the prevalence of depression was found. The OR (95% CI) for the first quintile of
      intake was 2.85 (1.49-5.45) and 2.18 (1.08-4.38), respectively, compared to the
      upper quintiles of intake (Q2-Q5) considered as a group. CONCLUSION: Low folate
      intake was associated with depression among currently smoking men and men with
      low anxiety levels. Low intake of vitamin B(12) was associated with depression
      among women. No significant associations were found for vitamin B(6) intake.

PMID- 19175491
TI  - The Association between health-related quality of life and prosthetic status and
      prosthetic needs in Taiwanese adults.
AB  - The objective of this study was to describe aspects of prosthetic statuses and
      needs and to evaluate their relationship with health-related quality of life in
      Taiwan. The study participants, aged 18 years and above, were recruited from a
      community survey, and each of the total 2469 participants received a dental
      examination and completed a questionnaire. Multivariable analysis was used to
      assess the adjusted means of health-related quality of life (SF-36) in both
      prosthetic status and need. The results showed that 12.6% of those aged 65 years
      and above were edentulous. The proportion of prosthetic need increased as age
      increased (39.7% to 61.3%). Multivariate analysis revealed that participants with
      'removable prosthesis' had higher physical health scores than those with 'non
      removable prosthesis'. The scores of mental health measurement decreased in
      people with need for full prostheses in relation to people without need for any
      prosthesis. Therefore, fulfilling prosthetic needs is not only about recovering
      oral masticatory function, but also concerns improvement of both physical and
      mental health-related quality of life.

PMID- 19175492
TI  - rFVIIa and a new enhanced rFVIIa-analogue, NN1731, reduce bleeding in clopidogrel
      treated and in thrombocytopenic rats.
AB  - BACKGROUND: The pharmacological effect of rFVIIa occurs at the surface of
      activated platelets by enhancing thrombin generation at the site of vascular
      damage. It is therefore important to study the effects of rFVIIa in platelet
      related bleeding situations. We examined the effect of rFVIIa and an rFVIIa
      analogue, NN1731, on clopidogrel-induced and thrombocytopenic bleeding in rats.
      METHODS AND RESULTS: Clopidogrel [10 mg kg(-1); per oral (p.o.)] severely
      inhibited platelet aggregation and increased blood loss after tail-transection
      four hours after administration. Treatment with rFVIIa (5, 10, 20 mg kg(-1)) or
      NN1731 (1, 5, 10 mg kg(-1)), administered five minutes after induction of
      bleeding, reduced blood loss significantly and dose-dependently. NN1731 had an
      increased hemostatic potential compared with rFVIIa, reducing blood loss to the
      control level, whereas this was not even achieved with the highest dose of
      rFVIIa. Antibody-induced thrombocytopenia reduced platelet numbers by more than
      90% and increased the blood loss after tail-transection. Treatment with 10 and 20
      mg kg(-1) rFVIIa significantly reduced blood loss, whereas 10 mg kg(-1) NN1731
      reduced the bleeding to control levels. CONCLUSIONS: The hemostatic effect of
      rFVIIa and NN1731 was demonstrated in thrombocytopenic and clopidogrel-treated
      rats, showing efficacy in situations with decreased platelet number or
      functionality. Our findings are consistent with the hypothesis that rFVIIa/NN1731
      contribute to hemostasis by thrombin generation even in situations with platelet
      disorders. Furthermore, NN1731 demonstrated a higher hemostatic potential than
      rFVIIa.

PMID- 19175493
TI  - Inflammation in deep vein thrombosis and the development of post-thrombotic
      syndrome: a prospective study.
AB  - BACKGROUND: The aim of this study was to investigate whether inflammatory markers
      (interleukin-6 [IL-6] and C-reactive protein [CRP]) in the acute phase of deep
      vein thrombosis (DVT) are associated with elevated venous outflow resistance
      (VOR), thrombosis score (TS), reflux and the development of clinical post
      thrombotic syndrome (PTS). METHODS: In 110 patients with a first DVT, plasma
      concentrations of IL-6 and CRP were determined on the day of admission. VOR, TS
      and reflux were measured 7 days, 1 and 3 months after diagnosis. After 1 year
      patients were evaluated for PTS using the Clinical, Etiologic, Anatomic and
      Pathophysiologic (CEAP) classification and Villalta scale. RESULTS: Median levels
      of IL-6 and CRP were 7 pg mL(-1) and 21 mg L(-1), respectively. After 3 months,
      VOR was elevated in 33 patients (30%), TS in 33 (30%) and reflux in 57 (52%).
      Incidence of PTS was 36.7% using CEAP>or=3 and 35.4% using Villalta-scale>or=5.
      Elevated levels of IL-6 and CRP were related to higher outcomes of VOR after 3
      months [relative risks (RR) 2.4 (95% CI 1.5-3.9) and 1.4 (1.1-3.3), respectively]
      and for IL-6 to TS [1.5 (1.1-2.1)]. For reflux no relation was found. After 90
      days, elevated outcomes of VOR, TS and reflux were related to PTS after 1 year.
      The association of IL-6 and CRP with PTS was weak using the CEAP classification
      with a RR of 1.2 (0.7-2.2) and 1.8 (0.9-3.3) and absent according to the Villalta
      scale 0.6 (0.2-1.4) and 1.2 (0.6-2.5), respectively. CONCLUSION: The results of
      this study suggest that inflammation might play a role in incomplete thrombus
      clearance, venous outflow obstruction and the development of PTS after 1 year.

PMID- 19175494
TI  - Cardiac involvement in acute thrombotic thrombocytopenic purpura: association
      with troponin T and IgG antibodies to ADAMTS 13.
AB  - INTRODUCTION: Evidence for cardiac involvement in thrombotic thrombocytopenic
      purpura (TTP) is uncommonly described. METHODOLOGY: We retrospectively reviewed
      41 patients assessing troponin T as a marker for cardiac involvement in acute TTP
      with clinical symptoms, electrocardiograms (ECG) and echocardiograms. A
      histopathological review of five patients who died of acute TTP was also
      undertaken. RESULTS: In 54% (22/41) of patients, troponin T was >or=0.05microg L(
      1) (normal range 0-0.01 microg L(-1)). Half (12/22) had cardiac symptoms and 8/22
      with a raised troponin T reported chest pain. ECG changes were present in 62% of
      patients with a raised troponin T. Median anti-ADAMTS 13 IgG antibody was
      significantly higher (P=0.018) in patients with troponin T>or=0.05 microg L(-1)
      (58.5% (range 17-162%), compared with patients with troponin T<0.05 microg L(-1)
      (35%, range 9-134%). Patients who died had higher troponin T levels (median 0.305
      microg L(-1)) and raised anti-ADAMTS 13 IgG (median 66.5%). On admission, there
      were no deaths in those with troponin T<or=0.04microg L(-1). Histology confirmed
      widespread myocardial microvascular thrombi. CONCLUSION: Clinical symptoms, ECG
      changes and echocardiograms are poor predictors of cardiac disease in acute TTP.
      Troponin T is specific for cardiac muscle and a sensitive marker of myocardial
      damage. In TTP patients, raised levels (>or=0.05 microg L(-1)) signify myocardial
      necrosis associated with microvascular thrombi. Mortality and acute morbidity was
      associated with higher admission troponin T and raised IgG antibody (>67%) to
      ADAMTS 13.

PMID- 19175495
TI  - Platelet adhesion to multimerin 1 in vitro: influences of platelet membrane
      receptors, von Willebrand factor and shear.
AB  - BACKGROUND: Multimerin 1 (MMRN1) is a large, homopolymeric adhesive protein,
      stored in platelets and endothelium, that when released, binds to activated
      platelets, endothelial cells and the extracellular matrix. OBJECTIVES: The goals
      of our study were to determine if (i) MMRN1 supports adhesion of resting and/or
      activated platelets under conditions of blood flow, and (ii) if MMRN1 enhances
      platelet adhesion to types I and III collagen. PATIENTS/METHODS: Platelet
      adhesion was evaluated using protein-coated microcapillaries, with or without
      added adhesive proteins and receptor antibodies. Platelets from healthy controls,
      Glanzmann thrombasthenia (GT) and severe von Willebrand factor (VWF)-deficient
      donors were tested. RESULTS: MMRN1 supported the adhesion of activated, but not
      resting, washed platelets over a wide range of shear rates. At low shear (150 s(
      1)), this adhesion was supported by integrins alphavbeta3 and glycoprotein (GP)
      Ibalpha but it did not require integrins alphaIIbbeta3 or VWF. At high shear
      (1500 s(-1)), adhesion to MMRN1 was supported by beta3 integrin-independent
      mechanisms, involving GPIbalpha and VWF, that did not require platelet activation
      when VWF was perfused over MMRN1 prior to platelets. MMRN1 bound to types I and
      III collagen, independent of VWF, however, its enhancing effects on platelet
      adhesion to collagen at high shear were VWF dependent. CONCLUSIONS: MMRN1
      supports platelet adhesion by VWF-dependent and -independent mechanisms that vary
      by flow rate. Additionally, MMRN1 binds to, and enhances, platelet adhesion to
      collagen. These findings suggest that MMRN1 could function as an adhesive ligand
      that promotes platelet adhesion at sites of vascular injury.

PMID- 19175496
TI  - Metabolic syndrome and risk of venous thromboembolism: Longitudinal Investigation
      of Thromboembolism Etiology.
AB  - SUMMARY BACKGROUND: In a recent case-control study, the odds of metabolic
      syndrome (MetSyn) among deep vein thrombosis cases were almost twice those among
      controls. We tested the hypothesis that the incidence of non-cancer-related
      venous thromboembolism (VTE) is higher among adults with MetSyn and further, that
      associations are stronger for idiopathic than secondary VTE. METHODS: A total of
      20 374 middle-aged and elderly adults were followed for over 12 years for
      incident VTE in the Longitudinal Investigation of Thromboembolism Etiology
      (LITE). All hospitalizations were identified and VTEs validated by chart review.
      Baseline MetSyn was defined using ATP III guidelines, including >or=3 of the
      following components: abdominal obesity, elevated blood pressure, low HDL
      cholesterol, high triglycerides and high glucose. Because sex modified the
      relation between MetSyn and VTE (p(interaction) = 0.001), proportional hazards
      regression analyses were stratified by sex to assess the associations of MetSyn
      and its components with risk of incident non-cancer-related VTE, adjusting for
      potential confounders. RESULTS: Incident VTE (n = 358) included 196 idiopathic
      events. Baseline MetSyn was associated with risk of total VTE (hazard ratio (HR)
      = 1.84, 95% CI = 1.30, 2.59) and idiopathic VTE (HR = 1.59, 95% CI = 1.02, 2.47)
      among men, but not women. The association was largely attributable to abdominal
      obesity (HR of VTE = 2.10, 95% CI = 1.51, 2.93, in men; HR of VTE = 1.70, 95% CI
      = 1.24, 2.34, in women), with no additional contribution by the other MetSyn
      components. CONCLUSION: Although abdominal obesity was associated with increased
      risk of VTE in both men and women, MetSyn and its other components do not seem
      important in VTE etiology.

PMID- 19175497
TI  - Definition of post-thrombotic syndrome of the leg for use in clinical
      investigations: a recommendation for standardization.
AB  - SUMMARY: The post-thrombotic syndrome (PTS) is increasingly recognized to be a
      common and important complication of deep venous thrombosis (DVT). Because there
      is no 'gold standard' objective test to establish its presence, PTS is diagnosed
      primarily on the basis of the presence of typical symptoms and clinical signs in
      a limb that was affected by DVT. As a wide variety of definitions of PTS have
      been used by researchers, it is difficult to compare data across studies and to
      formally combine data in meta-analyses. In a step towards standardization of the
      measurement of PTS in clinical studies, available scales and evidence to support
      their utility to diagnose PTS and to classify its severity were reviewed and
      discussed at the Control of Anticoagulation Subcommittee of the International
      Society on Thrombosis and Haemostasis (Vienna, July 2008).

PMID- 19175498
TI  - Elevated D-dimer levels predict recurrence in patients with idiopathic venous
      thromboembolism: a meta-analysis.
AB  - BACKGROUND: The evidence on the optimal duration of treatment in patients with an
      idiopathic venous thromboembolic event (VTE) is inconclusive. d-dimer testing to
      predict recurrent VTE has been evaluated in several studies. OBJECTIVES: We
      performed a meta-analysis of studies of patients with idiopathic VTE treated with
      oral anticoagulation therapy (OAT) to assess the prognostic value of elevated D
      dimer levels 1 month after discontinuation of OAT for VTE recurrence.
      PATIENTS/METHODS: The MEDLINE, EMBASE and Cochrane databases were searched to
      identify relevant studies. Studies were eligible for inclusion if they included
      patients with idiopathic VTE and in addition reported results for this group
      separately, had measured D-dimer approximately 1 month after discontinuation of
      OAT and had reported on recurrence of VTE. A random-effects model was used to
      pool study results. RESULTS: Data from four studies (1539 patients) were included
      in the current analysis. All studies reported on the number of recurrent events
      in the normal and elevated D-dimer groups. Overall, 125 of 751 patients (16.6%)
      with elevated D-dimer levels experienced recurrent VTE during the period of
      follow-up compared with 57 of 788 patients (7.2%) with normal D-dimer levels.
      Elevated D-dimer levels were significantly associated with recurrent VTE (odds
      ratio , 2.36; 95% CI, 1.65 to 3.36). CONCLUSIONS: Elevated d-dimer levels
      measured 1 month after discontinuation of OAT identify patients with idiopathic
      VTE at higher risk of recurrence.

PMID- 19175500
TI  - Variable extent of hybridization between invasive sika (Cervus nippon) and native
      red deer (C. elaphus) in a small geographical area.
AB  - Instances of hybridization between endemic and alien species pose a threat to
      species integrity but also provide us with an opportunity to study the dynamics
      of gene flow between two species as they first meet. Here, we used variation at
      22 highly differentiated microsatellite loci and one mitochondrial DNA (mtDNA)
      marker in a sample of 735 individuals, to investigate the genetic consequences of
      an introduction of Japanese sika deer (Cervus nippon) for native red deer (C.
      elaphus) on the Kintyre Peninsula in Scotland. We investigated population
      structure, estimated null-allele frequency and assigned individual hybrid scores
      using a Bayesian clustering algorithm implemented in structure 2.2. The dataset
      clearly divided into two clusters and generally, introgression into red and sika
      was low. However at one site, West Loch Awe, 43% of individuals were hybrids.
      MtDNA introgression indicated that hybridization was occurring between red-deer
      hinds and sika-deer stags. We argue that the pattern of differential
      introgression across the study area is primarily due to the rarity of
      hybridization events between the two species and the limited time the two species
      have been in contact (< 120 years). This contrasts with the causes of classic
      mosaic hybrid zones (selection induced by habitat variability). Currently, it
      seems possible that, in time, the level of hybridization found at West Loch Awe
      could also be found across the whole of the peninsula.

PMID- 19175499
TI  - Study of bioaccumulation of dalteparin at a prophylactic dose in patients with
      various degrees of impaired renal function.
AB  - BACKGROUND: Low-molecular-weight heparins (LMWH) have been shown to be effective
      and safe for prophylaxis of thromboembolic diseases. However, issues regarding
      safety and optimal use of LMWH arise in patients with renal insufficiency (RI).
      OBJECTIVES: To compare pharmacokinetic data of dalteparin for up to 3 weeks in
      patients with various degrees of RI. PATIENTS AND METHODS: Patients from general
      medical and surgical wards were included in this prospective cohort study and
      divided into three groups according to renal function: A=normal (GFR>or=60 mL
      min(-1)1.73 m(-2)), B=mild RI (GFR 30-59 mL min(-1)1.73 m(-2)), C=severe RI
      (GFR<30 mL min(-1)1.73 m(-2)). Dalteparin was injected s.c. once daily at a
      prophylactic dose. Peak anti-Xa activity levels (anti-Xa) were measured 4+/-1 h
      after injection on day 1 and every third day up to 3 weeks. Primary objectives
      were peak anti-Xa levels and adjusted anti-Xa levels, adjustment being carried
      out for dose and body weight. RESULTS: A total of 42 patients could be analyzed
      during a median of 10 days (interquartile range IQR 4-13, range 1-20). In all
      groups, adjusted peak anti-Xa levels were not different on day 10 compared with
      day 1. No bioaccumulation>30% could be found up to day 10 even in patients with
      severe RI. CONCLUSION: The use of dalteparin at a prophylactic dose was not
      associated with a bioaccumulation>30% even in patients with severe renal
      insufficiency during a median follow-up of 10 days (IQR 4-13, range 1-20).

PMID- 19175501
TI  - History and evolution of alpine plants endemic to the Qinghai-Tibetan Plateau:
      Aconitum gymnandrum (Ranunculaceae).
AB  - How Quaternary climatic oscillations affected range distributions and
      intraspecific divergence of alpine plants on the Qinghai-Tibetan Plateau (QTP)
      remains largely unknown. Here, we report a survey of chloroplast DNA (cpDNA) and
      nuclear ribosomal internal transcribed spacer (ITS) DNA variation aimed at
      exploring the phylogeographical history of the QTP alpine endemic Aconitum
      gymnandrum. We sequenced three cpDNA fragments (rpl20-rps12 intergenic spacer,
      the trnV intron and psbA-trnH spacer) and also the nuclear (ITS) region in 245
      individuals from 23 populations sampled throughout the species' range. Two
      distinct lineages, with eastern and western geographical distributions
      respectively, were identified from a phylogenetic analysis of ITS sequence
      variation. Based on a fast substitution rate, these were estimated to have
      diverged from each other in the early Pleistocene approximately 1.45 Ma. The
      analysis of cpDNA variation identified nine chlorotypes that clustered into two
      major clades that were broadly congruent in geographical distribution with the
      two ITS lineages. The east-west split of cpDNA divergence was supported by an
      amova which partitioned approximately half of the total variance between these
      two groups of populations. Analysis of the spatial distribution of chlorotypes
      showed that each clade was subdivided into two groups of populations such that a
      total of four population groups existed in the species. It is suggested that
      these different groups derive from four independent glacial refugia that existed
      during the Last Glacial Maximum (LGM), and that three of these refugia were
      located at high altitude on the QTP platform itself at that time. Coalescent
      simulation of chlorotype genealogies supported both an early Pleistocene origin
      of the two main cpDNA clades and also the 'four-refugia' hypothesis during the
      LGM. Two previous phylogeographical studies of QTP alpine plants indicated that
      such plants retreated to refugia at the eastern/south-eastern plateau edge during
      the LGM and/or previous glacial maxima. However, the results for A. gymnandrum
      suggest that at least some of these cold-tolerant species may have also survived
      centrally on the QTP platform throughout the Quaternary.

PMID- 19175502
TI  - Extreme changes to gene expression associated with homoploid hybrid speciation.
AB  - Hybridization is an important cause of abrupt speciation. Hybrid speciation
      without a change in ploidy (homoploid hybrid speciation) is well-established in
      plants but has also been reported in animals and fungi. A notable example of
      recent homoploid hybrid speciation is Senecio squalidus (Oxford ragwort), which
      originated in the UK in the 18th Century following introduction of hybrid
      material from a hybrid zone between S. chrysanthemifolius and S. aethnensis on
      Mount Etna, Sicily. To investigate genetic divergence between these taxa, we used
      complementary DNA microarrays to compare patterns of floral gene expression.
      These analyses revealed major differences in gene expression between the parent
      species and wild and resynthesized S. squalidus. Comparisons of gene expression
      between S. aethnensis, S. chrysanthemifolius and natural S. squalidus identified
      genes potentially involved in local environmental adaptation. The analysis also
      revealed non-additive patterns of gene expression in the hybrid relative to its
      progenitors. These expression changes were more dramatic and widespread in
      resynthesized hybrids than in natural S. squalidus, suggesting that a unique
      expression pattern may have been fixed during the allopatric divergence of
      British S. squalidus. We speculate that hybridization-induced gene-expression
      change may provide an immediate source of novel phenotypic variation upon which
      selection can act to facilitate homoploid hybrid speciation in plants.

PMID- 19175503
TI  - An AFLP clock for the absolute dating of shallow-time evolutionary history based
      on the intraspecific divergence of southwestern European alpine plant species.
AB  - The dating of recent events in the history of organisms needs divergence rates
      based on molecular fingerprint markers. Here, we used amplified fragment length
      polymorphisms (AFLPs) of three distantly related alpine plant species co
      occurring in the Spanish Sierra Nevada, the Pyrenees and the southwestern
      Alps/Massif Central to establish divergence rates. Within each of these species
      (Gentiana alpina, Kernera saxatilis and Silene rupestris), we found that the
      degree of AFLP divergence (D(N72)) between mountain phylogroups was significantly
      correlated with their time of divergence (as inferred from
      palaeoclimatic/palynological data), indicating constant AFLP divergence rates. As
      these rates did not differ significantly among species, a regression analysis
      based on the pooled data was utilized to generate a general AFLP rate. The
      application of this latter rate to AFLP data from other herbaceous plant species
      (Minuartia biflora: Schonswetter et al. 2006; Nigella degenii: Comes et al. 2008)
      resulted in a plausible timing of the recolonization of the Svalbard Islands and
      the separation of populations from the Alps and Scandinavia (Minuartia), and of
      island population separation in the Aegean Archipelago (Nigella). Furthermore,
      the AFLP mutation rate obtained in our study is of the same magnitude as AFLP
      mutation rates published previously. The temporal limits of our AFLP rate, which
      is based on intraspecific vicariance events at shallow (i.e. late glacial/Early
      Holocene) time scales, remains to be tested.

PMID- 19175504
TI  - Families in space: relatedness in the Barents Sea population of polar bears
      (Ursus maritimus).
AB  - The kin structure and dispersal pattern of polar bears (Ursus maritimus) of the
      Barents Sea was investigated during the spring mating season using two
      complementary approaches. First, individual genotypes based on the analyses of 27
      microsatellite loci of 583 polar bears were related to field information gathered
      from 1146 bears in order to reconstruct the animals' pedigrees and to infer
      geographical distances between adult bears of different relatedness categories.
      According to the data, the median natal dispersal distance of the male animals
      was 52 km while that of the females was 93 km. Second, the relatedness of pairs
      of adult bears was estimated and correlated to the geographical distance between
      them. The female dyads had a much stronger kin structure than the male dyads. The
      'pedigree approach' revealed a male kin structure which could not be detected
      using the 'relatedness approach'. This suggests that, on a broader scale,
      effective dispersal is slightly male biased. Despite fidelity to natal areas,
      male-mediated gene flow may nevertheless prevent genetic differentiation. Males
      might occasionally shift their home range which could therefore lead to a male
      biased breeding dispersal. Our results showed that a nonterritorial species such
      as the polar bear that has a high dispersal potential, lives in a highly unstable
      environment and migrates seasonally is still able to exhibit a distinct kin
      structure during the mating season.

PMID- 19175505
TI  - Morphological and molecular variation in tiger beetles of the Cicindela hybrida
      complex: is an 'integrative taxonomy' possible?
AB  - Current taxon assignments at the species level are frequently discordant with DNA
      based analyses. Recent studies on tiger beetles in the Cicindela hybrida complex
      identified discordance between mtDNA patterns and the entities currently defined
      by the taxonomic literature. To test the accuracy of morphologically delimited
      groups, five named taxa (species) from 24 representative sampling sites across
      Europe were scored for 41 external morphological characters. Three of the named
      taxa were 'diagnosable', that is, defined by between one and three characters
      unique to each group. Newly sequenced ITS1 and existing mitochondrial cox1
      markers established 20 and 22 different haplotypes, respectively, but only cox1
      produced (four) diagnosable units. Phylogenetic analysis and statistical
      parsimony networks showed poor congruence of character variation with the
      taxonomic entities (and each other). Variation in morphological characters was
      therefore tested directly for association with DNA-based nesting groups at
      various hierarchical levels using permutational contingency analysis. Significant
      statistical associations of 11 (of 13 variable) morphological characters were
      observed with nesting groups from ITS1 and mitochondrial DNA markers,
      predominantly at the 4-step level. The analysis demonstrates the need for formal
      tests of congruence with morphological variation at the level of individual
      characters, a step that is omitted from recent studies of 'integrative taxonomy'.
      In addition, statistical correlation of particular morphological characters with
      DNA-based nesting groups can identify the lowest hierarchical level at which
      various character sets show congruence, as a means to define evolutionarily
      separated entities supported by diverse data sources.

PMID- 19175506
TI  - Pleistocene divergence of Dinaric Drusus endemics (Trichoptera, Limnephilidae) in
      multiple microrefugia within the Balkan Peninsula.
AB  - The Balkan Peninsula is one of three major European refugial areas. It has high
      biodiversity and endemism, but data on the age and origin of its fauna,
      especially endemics, are limited. Mitochondrial sequence data (COI and 16S genes)
      were used to study the population structure and phylogeography of the caddisfly
      Drusus croaticus and the phylogeny and divergence of seven other Drusus species,
      mostly range-restricted endemics of the Dinaric region of the Balkan Peninsula.
      The divergence of D. croaticus populations in Croatia and allopatric Drusus
      species in Bosnia dated to the Pleistocene, showing the importance of this time
      period for the origin and diversification of Balkan endemic taxa. The divergence
      of more distantly related species dated to the Late Miocene/Early Pliocene.
      Population genetic and phylogeographic analysis of 115 individuals from 11
      populations of D. croaticus revealed a high level of genetic differentiation and
      absence of gene flow between populations separated by more than 10 km. The
      existence of allopatrically fragmented lineages in D. croaticus and the endemic
      Bosnian species is most likely the result of long-term isolation in multiple
      microrefugia, probably due to the specific habitat requirements and life-history
      traits of Drusinae coupled with the topographic complexity and historical changes
      in geomorphology of the region. Overall, these findings shed light on the
      processes generating the high genetic complexity of this refugial region that
      parallels the 'refugia within refugia' pattern widely reported from the Iberian
      refugium.

PMID- 19175507
TI  - Genetic relatedness and disrupted social structure in a poached population of
      African elephants.
AB  - We use genetic measures of relatedness and observations of female bonding to
      examine the demographic signature of historically heavy poaching of a population
      of free-ranging African elephants. We collected dung samples to obtain DNA and
      observed behaviour from 102 elephant families over a 25-month period in 2003-2005
      in Mikumi National Park, Tanzania. Poaching reduced the population by 75% in the
      decade prior to the 1989 ivory trade ban; park records indicate that poaching
      dropped significantly in Mikumi following the ban. Using 10 microsatellite loci,
      DNA was genotyped in 203 elephants and pair-wise relatedness was calculated among
      adult females within and between groups. The Mikumi population is characterized
      by small group size, considerable variation in group relatedness, females with no
      first-order adult relatives and females that form only weak social bonds. We used
      gene-drop analysis and a model of a genetically intact pedigree to compare our
      observed Mikumi group relatedness to a simulated genetically intact unpoached
      expectation. The majority of groups in Mikumi contain 2 to 3 adults; of these,
      45% were classified as genetically disrupted. Bonding, quantified with a pair
      wise association index, was significantly correlated with relatedness; however
      only half of the females formed strong bonds with other females, and relatedness
      was substantially lower for a given bond strength as compared to an unpoached
      population. Female African elephants without kin demonstrated considerable
      behavioural plasticity in this disturbed environment, grouping with other females
      lacking kin, with established groups, or remaining alone, unable to form any
      stable adult female-bonds. We interpret these findings as the remaining effect of
      poaching disturbance in Mikumi, despite a drop in the level of poaching since the
      commercial trade in ivory was banned 15 years ago.

PMID- 19175508
TI  - Survival in the Rockies of an endangered hybrid swarm from diverged caribou
      (Rangifer tarandus) lineages.
AB  - In North America, caribou (Rangifer tarandus) experienced diversification in
      separate refugia before the last glacial maximum. Geographical isolation produced
      the barren-ground caribou (Rangifer tarandus groenlandicus) with its distinctive
      migratory habits, and the woodland caribou (Rangifer tarandus caribou), which has
      sedentary behaviour and is now in danger of extinction. Herein we report on the
      phylogenetics, population structure, and migratory habits of caribou in the
      Canadian Rockies, utilizing molecular and spatial data for 223 individuals.
      Mitochondrial DNA analyses show the occurrence of two highly diverged lineages;
      the Beringian-Eurasian and North American lineages, while microsatellite data
      reveal that present-day Rockies' caribou populations have resulted from
      interbreeding between these diverged lineages. An ice-free corridor at the end of
      the last glaciation likely allowed, for the first time, for barren-ground caribou
      to migrate from the North and overlap with woodland caribou expanding from the
      South. The lack of correlation between nuclear and mitochondrial data may
      indicate that different environmental forces, which might also include human
      caused habitat loss and fragmentation, are currently reshaping the population
      structure of this postglacial hybrid swarm. Furthermore, spatial ecological data
      show evidence of pronounced migratory behaviour within the study area, and
      suggest that the probability of being migratory may be higher in individual
      caribou carrying a Beringian-Eurasian haplotype which is mainly associated with
      the barren-ground subspecies. Overall, our analyses reveal an intriguing example
      of postglacial mixing of diverged lineages. In a landscape that is changing due
      to climatic and human-mediated factors, an understanding of these dynamics, both
      past and present, is essential for management and conservation of these
      populations.

PMID- 19175510
TI  - Long-term effectiveness of diet-plus-exercise interventions vs. diet-only
      interventions for weight loss: a meta-analysis.
AB  - Diet and exercise are two of the commonest strategies to reduce weight. Whether a
      diet-plus-exercise intervention is more effective for weight loss than a diet
      only intervention in the long-term has not been conclusively established. The
      objective of this study was to systemically review the effect of diet-plus
      exercise interventions vs. diet-only interventions on both long-term and short
      term weight loss. Studies were retrieved by searching MEDLINE and Cochrane
      Library (1966 - June 2008). Studies were included if they were randomized
      controlled trials comparing the effect of diet-plus-exercise interventions vs.
      diet-only interventions on weight loss for a minimum of 6 months among obese or
      overweight adults. Eighteen studies met our inclusion criteria. Data were
      independently extracted by two investigators using a standardized protocol. We
      found that the overall standardized mean differences between diet-plus-exercise
      interventions and diet-only interventions at the end of follow-up were -0.25 (95%
      confidence interval [CI]-0.36 to -0.14), with a P-value for heterogeneity of 0.4.
      Because there were two outcome measurements, weight (kg) and body mass index (kg
      m(-2)), we also stratified the results by weight and body mass index outcome. The
      pooled weight loss was 1.14 kg (95% CI 0.21 to 2.07) or 0.50 kg m(-2) (95% CI
      0.21 to 0.79) greater for the diet-plus-exercise group than the diet-only group.
      We did not detect significant heterogeneity in either stratum. Even in studies
      lasting 2 years or longer, diet-plus-exercise interventions provided
      significantly greater weight loss than diet-only interventions. In summary, a
      combined diet-plus-exercise programme provided greater long-term weight loss than
      a diet-only programme. However, both diet-only and diet-plus-exercise programmes
      are associated with partial weight regain, and future studies should explore
      better strategies to limit weight regain and achieve greater long-term weight
      loss.

PMID- 19175509
TI  - Have we entered the brown adipose tissue renaissance?
AB  - In the 1970s and 1980s, it was observed that rodents could offset excess calories
      ingested when they were fed a human-like 'cafeteria diet'. Although it was
      erroneously concluded that this so-called diet-induced thermogenesis was because
      of brown adipose tissue (BAT), it led to efforts to test whether variations in
      brown fat in humans may explain the susceptibility to obesity. However, from
      evidence on the inability of ephedrine or beta-3 adrenergic agonists to induce
      BAT thermogenesis, it was concluded that the thermogenic role of BAT was
      unimportant in adult humans largely because humans had low numbers of brown
      adipocytes. Solid evidence on the actual numbers of brown adipocytes in humans
      was not available. We are now re-evaluating the role of BAT for the treatment of
      obesity given the following recent observations (i) studies in nuclear medicine
      by using PET/CT scanning reveal the presence of BAT in adult humans; and (ii)
      recent data suggest that a new transcription factor called PDRM16 may control the
      induction of BAT. These recent discoveries should revamp our effort to target the
      molecular development of brown adipogenesis in the treatment of obesity.

PMID- 19175511
TI  - State of the world's children with diabetes.
AB  - As one considers the near future of diabetes in children, some very sobering
      thoughts are in order. First, with respect to the magnitude of the problem, the
      worst is yet to come! The emergence of new economic giants such as China and
      India will bring with it potential massive increases in type 1 diabetes (2-5% per
      annum increases in incidence in the world's most populous countries) and
      childhood obesity (with its associated insulin resistance and type 2 diabetes).
      This will demand the training of enormous numbers of health care professionals
      and delivery of insulin and testing equipment that is of high quality and
      reasonable cost. Second, the majority of children with diabetes presently do not
      and, likely in the foreseeable future, will not achieve and maintain levels of
      metabolic control that provide protection from microvascular and macrovascular
      complications. In fact, an analysis by the Centers for Disease Control in the USA
      suggested that a child of 10 yr of age developing diabetes in the year 2000 would
      live a further approximately 50-55 yr, losing about 18-20 yr of life, this in the
      world's richest nation!Finally, Edwin Gale in 2005 issued the following warning:
      'The individual and communal legacy of poor glucose control will remain with us
      for the next 30 years, EVEN if an effective means of preventing new cases of the
      disease were to be introduced tomorrow'.There is much work to be done and little
      room for complacency. Only when every single child with diabetes has ready access
      to experienced health care professionals, insulin, and other supplies, food water
      and protection will the first part of the job be done.

PMID- 19175512
TI  - Use of a subcutaneous injection port to improve glycemic control in children with
      type 1 diabetes.
AB  - OBJECTIVE: To determine if use of an injection port, the Insuflon, would help to
      improve glycemic control in youth with type 1 diabetes (TID) who were in
      suboptimal glycemic control (hemoglobin A1c, HbA1c >8.0%). STUDY DESIGN: A three
      arm randomized protocol was used to study the effects of the Insuflon (a
      subcutaneous injection port) vs. an alarmable blood glucose meter vs. a control
      group on glycemic control in 66 youth with T1D. All participants used insulin
      glargine as their basal insulin and the NovoPen Junior with insulin aspart as
      their rapid-acting insulin. Participants were randomized into control, alarm, or
      Insuflon groups. HbA1c levels were the primary outcome with values at baseline,
      3, and 6 months. RESULTS: Initial parameters were similar in the three groups.
      HbA1c values were significantly lower for youth who used the Insuflon than for
      the control group at 3 and 6 months (p = 0.025). The HbA1c values (in %) for
      youth using the Insuflon decreased significantly from 9.4 at screening to 8.7 at
      3 months (p < 0.001) and 8.5 at 6 months (p < 0.001). There were no significant
      reductions (p > or = 0.05) in the HbA1c values within the other two groups.
      CONCLUSION: The Insuflon injection port helps some youth with T1D to improve
      glycemic control.

PMID- 19175514
TI  - Successful treatment of refractory Langerhans cell histiocytosis with pulmonary
      aspergillosis by reduced-intensity conditioning cord blood transplantation.
AB  - The prognosis of multisystem LCH in children with risk organ involvement is
      extremely poor when they fail to respond to conventional chemotherapy. In such
      patients, allogeneic SCT may produce complete and sustained remission; however,
      high-dose myeloablative regimens are frequently associated with treatment-related
      morbidity and mortality. More recently, allogeneic SCT following an RIC regimen
      has been performed as an alternative salvage approach. We describe a nine-month
      old boy with refractory multisystem LCH with pulmonary aspergillosis who was
      successfully treated with reduced-intensity cord blood transplantation.

PMID- 19175513
TI  - Ocular complications in children and adolescents following renal transplantation.
AB  - Ocular complications after renal transplantation are common in adults.
      Nevertheless, data regarding these complications in children are insufficient.
      The purpose of the present study was to assess ocular morbidity in pediatric
      renal graft recipients. A retrospective observational study of 71 patients aged
      11.2 +/- 5.5 yr was conducted. Mean duration of follow-up was 5.6 +/- 3.5 yr. A
      total of 16 ocular complications were found in 12 (17%) of the patients. Three
      patients suffered from more than one complication. Cataract was the most common
      finding (six patients, 8.4%) followed by swollen disk and hypertensive
      retinopathy in four patients (5.7%) each and increased intra-ocular pressure in
      two patients (3%). Mean time interval between transplantation and occurrence of
      first abnormal ocular finding was 37 +/- 34.5 months. The follow-up time was
      significantly longer in patients with ophthalmological problems than in those
      without complications (7.8 yr vs. 5.2 yr, p < 0.02). No statistically significant
      association was found between the occurrence of ocular complications and the age
      of the patients at transplantation, donor source, duration of dialysis prior to
      transplantation, previous corticosteroid therapy or presence of acute rejection
      episodes. The results of the study point to the importance of regular concurrent
      ophthalmological follow-up in pediatric renal graft recipients to reduce/prevent
      ocular morbidity.

PMID- 19175515
TI  - BK virus nephropathy in the native kidneys of a pediatric heart transplant
      recipient.
AB  - BK virus is a human polyoma virus that may cause nephropathy in immunosuppressed
      patients. It is a well-recognized cause of renal allograft dysfunction and
      allograft loss in renal transplant recipients, but it is an infrequent cause of
      nephropathy outside this setting. There are a few case reports of BK virus
      nephropathy in the native kidneys of immunosuppressed adult patients with non
      renal transplants, but so far it has not been reported in pediatric non-renal
      solid organ transplant recipients. We report a case of a seven-yr-old heart
      transplant patient who was diagnosed with BK virus nephropathy, eight months
      after his second heart transplant. Despite intervention, his renal dysfunction
      progressed to renal failure. He is currently receiving maintenance hemodialysis
      and awaiting renal transplantation. It is important to recognize BK virus
      infection as a possible cause of renal dysfunction in immunosuppressed children
      who are non-renal transplant recipients.

PMID- 19175516
TI  - Reverse portal flow after liver transplantation--ominous or acceptable?
AB  - Reversal of portal flow or hepatofugal flow after liver transplantation is a rare
      complication after liver transplantation. The available reports in the literature
      suggest that it is an ominous condition that requires immediate operative
      intervention, failing which prognosis would be grim. We report two children from
      two different centers who developed hepatofugal flow in the immediate post
      operative period after liver transplantation. The possible etiologies in these
      patients were acute rejection in one and absence of an MHV causing inadequate
      hepatic venous outflow in the other. Both patients were treated non-operatively
      with steroids and immunosuppression. Spontaneous reversal to a normal hepatopetal
      flow occurred in both and the patients continue to be well six months after the
      transplant. Our experience contradicts the viewpoint that hepatofugal flow
      equates to mortality in the absence of surgical intervention. It remains to be
      defined as to which patients with hepatofugal flow will benefit from surgical
      intervention.

PMID- 19175517
TI  - The value of immunoprophylaxis for cytomegalovirus infection with intravenous
      immunoglobulin in pediatric liver transplant recipients receiving a low-dose
      immunosupressive regimen.
AB  - The incidence of CMV infection following pediatric Ltx is particularly high,
      which can be attributed to the increased number of patients at high risk for
      primary infection (donor CMV+, recipient CMV-). Current approaches to cope with
      this complication producing post-operative morbidity include prophylactic or
      preemptive ganciclovir therapy. As the risk for symptomatic CMV infection is
      directly correlated with the intensity of immunosuppression, the aim of our study
      was to assess the value of IVIG in order to protect children receiving low-dose
      immunosuppression from CMV disease. Twenty-eight consecutive children (median age
      62.2 months) at high risk prospectively received three infusions of IVIG on days
      four, 14, and 28 post-transplant and were monitored for six months post-Ltx.
      Immunosuppression consisted of cyclosporine (initial trough levels 170-200
      microg/L) and prednisolone (starting dose 15 mg/m(2)) as well as basiliximab
      induction therapy. Patient survival was 100% and graft survival was 92.9%. Two
      subjects developed laboratory findings of CMV infection (8%) and one child
      suffered from tissue invasive CMV disease (4%). Three patients were excluded from
      the study because of protocol violations. We conclude that there was a low
      incidence of CMV disease among a prospective cohort receiving low-dose
      immunosuppression and a standard IVIG product.

PMID- 19175518
TI  - Ethylene reduces gas exchange and growth of lettuce plants under hypobaric and
      normal atmospheric conditions.
AB  - Elevated levels of ethylene occur in controlled environment agriculture and in
      spaceflight environments, leading to adverse plant growth and sterility. The
      objectives of this research were to characterize the influence of ethylene on
      carbon dioxide (CO(2)) assimilation (C(A)), dark period respiration (DPR) and
      growth of lettuce (Lactuca sativa L. cv. Buttercrunch) under ambient and low
      total pressure conditions. Lettuce plants were grown under variable total gas
      pressures of 25 kPa (hypobaric) and 101 kPa (ambient) pressure. Endogenously
      produced ethylene accumulated and reduced C(A), DPR and plant growth of ambient
      and hypobaric plants. There was a negative linear correlation between increasing
      ethylene concentrations [from 0 to around 1000 nmol mol(-1) (ppb)] on C(A), DPR
      and growth of ambient and hypobaric plants. Declines in C(A) and DPR occurred
      with both exogenous and endogenous ethylene treatments. C(A) was more sensitive
      to increasing ethylene concentration than DPR. There was a direct, negative
      effect of increasing ethylene concentration reducing gas exchange as well as an
      indirect ethylene effect on leaf epinasty, which reduced light capture and C(A).
      While the C(A) was comparable, there was a lower DPR in hypobaric than ambient
      pressure plants - independent of ethylene and under non-limiting CO(2) levels
      (100 Pa pCO(2), nearly three-fold that in normal air). This research shows that
      lettuce can be grown under hypobaria ( congruent with25% of normal earth ambient
      total pressure); however, hypobaria caused no significant reduction of endogenous
      ethylene production.

PMID- 19175519
TI  - Efficient virus-induced gene silencing in plants using a modified geminivirus
      DNA1 component.
AB  - Virus-induced gene silencing (VIGS) is currently recognized as a powerful reverse
      genetics tool for application in functional genomics. DNA1, a satellite-like and
      single-stranded DNA molecule associated with begomoviruses (Family
      Geminiviridae), has been shown to replicate autonomously but requires the helper
      virus for its dissemination. We developed a VIGS vector based on the DNA1
      component of tobacco curly shoot virus (TbCSV), a monopartite begomovirus, by
      inserting a multiple cloning site between the replication-associated protein open
      reading frame and the A-rich region for subsequent insertion of DNA fragments of
      genes targeted for silencing. When a host gene (sulphur, Su) or transgene (green
      fluorescent protein, GFP) was inserted into the modified DNA1 vector and co
      agroinoculated with TbCSV, efficient silencing of the cognate gene was observed
      in Nicotiana benthamiana plants. More interestingly, we demonstrated that this
      modified DNA1 could effectively suppress GFP in transgenic N. benthamiana or
      endogenous Su in tobacco plants when co-agroinoculated with tomato yellow leaf
      curl China virus (TYLCCNV), another monopartite begomovirus that does not induce
      any viral symptoms. A gene-silencing system in Nicotiana spp., Solanum
      lycopersicum and Petunia hybrida plants was then established using TYLCCNV and
      the modified DNA1 vector. The system can be used to silence genes involved in
      meristem and flower development. The modified DNA1 vector was used to silence the
      AtTOM homologous genes (NbTOM1 and NbTOM3) in N. benthamiana. Silencing of NbTOM1
      or NbTOM3 can reduce tobamovirus multiplication to a lower level, and silencing
      of both genes simultaneously can completely inhibit tobamovirus multiplication.
      Previous studies have reported that DNA1 is associated with both monopartite and
      bipartite begomoviruses, as well as curtoviruses. This vector system can
      therefore be applied for the study, analysis and discovery of gene function in a
      variety of important crop plants.

PMID- 19175520
TI  - Analysis of promoters in transgenic barley and wheat.
AB  - Advances in the genetic transformation of cereals have improved the prospects of
      using biotechnology for plant improvement, and a toolbox of promoters with
      defined specificities would be a valuable resource in controlling the expression
      of transgenes in desired tissues for both plant improvement and molecular
      farming. A number of promoters have been isolated from the important cereals
      (wheat, barley, rice and maize), and these promoters have been tested mostly in
      homologous cereal systems and, to a lesser extent, in heterologous cereal
      systems. The use of these promoters across the important cereals would add value
      to the utility of each promoter. In addition, promoters with less sequence
      homology, but with similar specificities, will be crucial in avoiding homology
      based gene silencing when expressing more than one transgene in the same tissue.
      We have tested wheat and barley promoters in transgenic barley and wheat to
      determine whether their specificity is shared across these two species. The
      barley bifunctional alpha-amylase/subtilisin inhibitor (Isa) promoter, specific
      to the pericarp in barley, failed to show any activity in wheat, whereas the
      wheat early-maturing (Em) promoter showed similar activity in wheat and barley.
      The wheat high-molecular-weight glutenin (HMW-Glu) and barley D-hordein (D-Hor)
      and B-hordein (B-Hor) storage protein promoters maintained endosperm-specific
      expression of green fluorescent protein (GFP) in wheat and barley, respectively.
      Using gfp, we have demonstrated that the Isa and Em promoters can be used as
      strong promoters to direct transgenes in specific tissues of barley and wheat
      grain. Differential promoter activity across cereals expands and adds value to a
      promoter toolbox for utility in plant biotechnology.

PMID- 19175521
TI  - Root-selective expression of AtCAX4 and AtCAX2 results in reduced lamina cadmium
      in field-grown Nicotiana tabacum L.
AB  - To assess the impact of enhanced root vacuole cadmium (Cd) sequestration on leaf
      Cd accumulation under a low Cd dose, as generally occurs in agriculture, leaf Cd
      accumulation was examined in field-grown tobacco plants expressing genes encoding
      the high-capacity-Cd, tonoplast-localized, divalent cation/H antiporters AtCAX4
      and AtCAX2 (AtCAX, Arabidopsis cation exchanger). It has been shown previously
      that root tonoplast vesicles isolated from plants expressing these genes,
      directed by root-selective promoters, show enhanced Cd transport activity, and
      young plants show enhanced root Cd accumulation when grown in solution culture
      containing 0.02 microM Cd, a moderate Cd dose. In this article, we present
      results which show that the lower leaves of mature plants expressing AtCAX2 or
      AtCAX4, under the control of two different root-selective promoters, accumulate
      15%-25% less lamina Cd than control plants when grown in the field (3 years,
      three different collection methods). Reciprocal grafting experiments of AtCAX2
      shoots onto control roots (and vice versa), grown in solution culture with 0.005
      microM Cd, indicated that the root controls Cd translocation and accumulation in
      the shoot in control and AtCAX2 and AtCAX4 tobacco plants exposed to low Cd
      concentration. The results are consistent with a model in which supplementation
      of Cd/H antiporter activity in root cell tonoplasts enhances root Cd
      sequestration, resulting in decreased translocation of Cd to the shoot of field
      grown plants. These results suggest that human Cd intake from food and tobacco
      use could be reduced via the enhancement of root vacuolar sequestration of this
      pollutant.

PMID- 19175522
TI  - Are suberythemal doses of ultraviolet B good for your skin?

PMID- 19175523
TI  - Lentivirus-mediated bifunctional cell labeling for in vivo melanoma study.
AB  - Lentiviral vectors (LVs) are capable of labeling a broad spectrum of cell types,
      achieving stable expression of transgenes. However, for in vivo studies, the
      duration of marker gene expression has been highly variable. We have developed a
      series of LVs harboring different promoters for expressing reporter gene in mouse
      cells. Long-term culture and colony formation of several LV-labeled mouse
      melanoma cells showed that promoters derived from mammalian house-keeping genes,
      especially those encoding RNA polymerase II (Pol2) and ferritin (FerH), provided
      the highest consistency for reporter expression. For in vivo studies, primary
      B16BL6 mouse melanoma were infected with LVs whose luciferase-green fluorescence
      protein fusion gene (Luc/GFP) was driven by either Pol2 or FerH promoters. When
      transplanted into syngeneic C57BL/6 mice, Luc/GFP-labeled B16BL6 mouse melanoma
      cells can be monitored by bioluminescence imaging in vivo, and GFP-positive cells
      can be isolated from the tumors by fluorescence-activated cell sorter. Pol2
      Luc/GFP labeling, while lower in activity, was more sustainable than FerH-Luc/GFP
      labeling in B16BL6 over consecutive passages into mice. We conclude that Pol-2
      Luc/GFP labeling allows long-term in vivo monitoring and tumor cell isolation in
      immunocompetent mouse melanoma models.

PMID- 19175525
TI  - CTLA4 and generalized vitiligo: two genetic association studies and a meta
      analysis of published data.
AB  - Several lines of evidence have implicated the gene encoding cytotoxic T
      lymphocyte antigen 4 (CTLA4) in susceptibility to various autoimmune diseases.
      However, published studies of genetic association between CTLA4 polymorphisms and
      vitiligo have yielded conflicting results. Here, we describe two new genetic
      association studies of CTLA4 single-nucleotide polymorphisms (SNPs) and
      generalized vitiligo in two independent Romanian Caucasian (CEU) case-control
      cohorts. The first study, of SNPs rs1863800, rs231806, rs231775, rs3087243,
      rs11571302, rs11571297, and rs10932037, showed no allelic, genotypic, or
      haplotypic association with generalized vitiligo. The second study, of SNP
      rs231775, likewise showed no significant association. To enhance statistical
      power over that of any individual study, we carried out a meta-analysis that
      incorporated these two new studies and all other published genetic association
      studies of CTLA4 SNPs and vitiligo in CEU populations. While there was no
      association with vitiligo overall, the meta-analysis showed significant
      association of SNP rs231775 in that subgroup of vitiligo patients who also had
      other concomitant autoimmune diseases. Similarly, there was near-significant
      association in this same patient subgroup with several other CTLA4 SNPs that are
      in linkage disequilibrium with rs231775. Our results indicate that the
      association of CTLA4 with vitiligo is weak, and indeed may be secondary, driven
      by primary genetic association of CTLA4 with other autoimmune diseases that are
      epidemiologically associated with vitiligo.

PMID- 19175524
TI  - BI-69A11-mediated inhibition of AKT leads to effective regression of xenograft
      melanoma.
AB  - The AKT/PKB pathway plays a central role in tumor development and progression and
      is often up-regulated in different tumor types, including melanomas. We have
      recently reported on the in silico approach to identify putative inhibitors for
      AKT/PKB. Of the reported hits, we selected BI-69A11, a compound which was shown
      to inhibit AKT activity in in vitro kinase assays. Analysis of BI-69A11 was
      performed in melanoma cells, a tumor type that commonly exhibits up-regulation of
      AKT. Treatment of the UACC903 human melanoma cells, harboring the PTEN mutation,
      with BI-69A11 caused efficient inhibition of AKT S473 phosphorylation with
      concomitant inhibition of AKT phosphorylation of PRAS40. Treatment of melanoma
      cells with BI-69A11 also reduced AKT protein expression, which coincided with
      inhibition of AKT association with HSP-90. BI-69A11 treatment not only caused
      cell death of melanoma, but also prostate tumor cell lines. Notably, the effect
      of BI-69A11 on cell death was more pronounced in cells that express an active
      form of AKT. Significantly, intra-peritoneal injection of BI-69A11 caused
      effective regression of melanoma tumor xenografts, which coincided with elevated
      levels of cell death. These findings identify BI-69A11 as a potent inhibitor of
      AKT that is capable of eliciting effective regression of xenograft melanoma
      tumors.

PMID- 19175526
TI  - Do early nouns refer to kinds or distinct shapes? Evidence from 10-month-old
      infants.
AB  - What is the nature of early words? Specifically, do infants expect words for
      objects to refer to kinds or to distinct shapes? The current study investigated
      this question by testing whether 10-month-olds expect internal object properties
      to be predicted by linguistic labels. A looking-time method was employed. Infants
      were familiarized with pairs of identical or different objects that made
      identical or different sounds. During test, before the sounds were demonstrated,
      paired objects were labeled with one repeated count-noun label or two distinct
      labels. Results showed that infants expected objects labeled with distinct labels
      to make different sounds and objects labeled with repeated labels to make
      identical sounds, regardless of the objects' appearance. These findings indicate
      that the 10-month-olds' expectations about internal properties of objects were
      driven by labeling and provide evidence that even at the beginning of word
      learning, infants expect distinct labels to refer to different kinds.

PMID- 19175527
TI  - To brake or accelerate when the light turns yellow? Stress reduces older adults'
      risk taking in a driving game.

PMID- 19175528
TI  - Age, race, and implicit prejudice: using process dissociation to separate the
      underlying components.
AB  - Older adults express greater prejudice than younger adults, but it is not clear
      why. In a community-based sample, we found that older White adults demonstrated
      more racial prejudice on an implicit measure, the race Implicit Association Test,
      than did younger adults. Process-dissociation procedures indicated that this
      difference in implicit prejudice was due to older adults having less control of
      their automatic prejudicial associations rather than stronger automatic
      prejudicial associations. Furthermore, this age difference in control was
      mediated by age-related deficits in inhibitory ability. White participants showed
      stronger automatic prejudicial associations than did Black participants.

PMID- 19175529
TI  - Fear extinction to an out-group face: the role of target gender.
AB  - Conditioning studies on humans and other primates show that fear responses
      acquired toward danger-relevant stimuli, such as snakes, resist extinction,
      whereas responses toward danger-irrelevant stimuli, such as birds, are more
      readily extinguished. Similar evolved biases may extend to human groups, as
      recent research demonstrates that a conditioned fear response to faces of persons
      of a social out-group resists extinction, whereas fear toward a social in-group
      is more readily extinguished. Here, we provide an important extension to previous
      work by demonstrating that this fear-extinction bias occurs solely when the
      exemplars are male. These results underscore the importance of considering how
      gender of the target stimulus affects psychological and physiological responses
      to out-group threat.

PMID- 19175530
TI  - The cutest little baby face: a hormonal link to sensitivity to cuteness in infant
      faces.
AB  - We used computer image manipulation to develop a test of perception of subtle
      gradations in cuteness between infant faces. We found that young women (19-26
      years old) were more sensitive to differences in infant cuteness than were men
      (19-26 and 53-60 years old). Women aged 45 to 51 years performed at the level of
      the young women, whereas cuteness sensitivity in women aged 53 to 60 years was
      not different from that of men (19-26 and 53-60 years old). Because average age
      at menopause is 51 years in Britain, these findings suggest the possible
      involvement of reproductive hormones in cuteness sensitivity. Therefore, we
      compared cuteness discrimination in pre- and postmenopausal women matched for age
      and in women taking and not taking oral contraceptives (progestogen and
      estrogen). Premenopausal women and young women taking oral contraceptives (which
      raise hormone levels artificially) were more sensitive to variations of cuteness
      than their respective comparison groups. We suggest that cuteness sensitivity is
      modulated by female reproductive hormones.

PMID- 19175531
TI  - The evolving ecology of risk for hospitalized dialysis patients.
AB  - Despite an increased focus on patient safety, changes in resident work rules and
      contemporary hospital culture often combine to create an environment of potential
      hazard for the hospitalized dialysis patient. Clinical scenarios are presented to
      illustrate some of these risks, and suggestions are offered for the protection of
      patients.

PMID- 19175532
TI  - Intersecting guidelines: administering erythropoiesis-stimulating agents to
      chronic kidney disease patients with cancer.
AB  - There has been a dramatic sea change in the use of erythropoiesis-stimulating
      agents (ESAs) for anemic persons with chronic kidney disease (CKD) or cancer
      patients undergoing chemotherapy. An important area that has not been addressed
      previously is a CKD patient who also has a malignancy. Clinical guidelines exist
      that outline recommended treatments for each disease, but the intersection of the
      two disease processes presents difficult decisions for patients and physicians.
      Herein, we review the background underlying recent revisions in clinical alerts
      and guidelines for ESAs, and provide guidance for treating anemia among CKD
      patients who are receiving no therapy, chemotherapy with curative intent, or
      chemotherapy with palliative intent. The guiding principle is that comprehensive
      assessment of risks and benefits in the relevant clinical setting is imperative.

PMID- 19175534
TI  - Activated vitamin D: does it explain an apparent survival advantage among black
      and hispanic hemodialysis patients?

PMID- 19175535
TI  - Stent migration and folding in the subclavian vein during subclavian hemodialysis
      catheter placement.
AB  - The role of stent placement in hemodialysis (HD) access intervention continues to
      evolve. As more stents are placed, new and unusual complications are coming to
      light. We describe a case in which an unsuccessful attempt to place a left
      subclavian dialysis catheter resulted in the inadvertent migration and folding of
      a previously deployed subclavian stent. Attempts to remove the stent with a snare
      were unsuccessful. Patency was restored to the access circuit by placing a new
      stent through the struts of the folded one. Clinical vascular practice guidelines
      for vascular access on the use of fluoroscopy for temporary HD catheter placement
      may need to be re-evaluated with the reported increase in stent placement in the
      US HD population.

PMID- 19175536
TI  - Nonoperative salvage of an aneurysmal arteriovenous fistula.

PMID- 19175537
TI  - Hemoglobin control, ESA resistance, and regular low-dose IV iron therapy: a
      review of the evidence.
AB  - Anemia management in hemodialysis patients has progressed following the
      introduction of erythropoiesis-stimulating agents (ESAs) and intravenous (IV)
      iron. However, maintaining a stable hemoglobin (Hb) level can be challenging.
      Patient comorbidities and variable dosage administrations of ESA therapy can lead
      to great variability in Hb concentrations over time. Fluctuating Hb levels is
      associated with increased complications. This article reviews factors that affect
      Hb control, with a focus on management practices (e.g., regular low-dose
      administration of IV iron) that can help improve anemia management.

PMID- 19175538
TI  - Distal digital embolization from a thrombosed aneurysmal hemodialysis
      arteriovenous fistula: the benefit of a hybrid approach.
AB  - Aneurysmal degeneration of a hemodialysis arteriovenous fistula (AVF) is common;
      however, distal digital embolization from an AVF is extremely rare. Even though
      the ultimate fate of all arteriovenous hemodialysis access is thrombosis with
      minimal consequences, dislodgement of thrombus at the proximal anastomosis could
      lead to ischemia of the distal arterial circulation. We here present a case of a
      renal transplant patient with a thrombosed aneurysmal AVF who presented with
      acute digital ischemia successfully treated with combination catheter-directed
      thrombolysis and open repair. No similar report was found describing this entity
      treated with this approach.

PMID- 19175539
TI  - Touch, grasp, deliver and control: functional cross-talk between microtubules and
      cell adhesions.
AB  - Cross-talk between microtubule networks and sites of cell-matrix and cell-cell
      adhesion has profound impact on these structures and is essential for proper cell
      organization, polarization and motility. Components of adhesion sites can
      interact directly with microtubules or with proteins that specifically associate
      with microtubule plus ends and minus ends and in this way capture, stabilize or
      destabilize microtubules. In their turn, microtubules can serve as routes for
      delivery of structural and regulatory factors that control adhesion site
      turnover. In addition, the microtubule lattice or growing microtubule plus ends
      can serve as diffusional sinks that accumulate and scaffold regulatory molecules,
      thereby affecting their activity in the vicinity of adhesions. Combination of
      these mechanisms underlies the functional co-operation between microtubules and
      adhesion sites and defines their dynamic behavior.

PMID- 19175540
TI  - Outcome of influenza infections in outpatients after allogeneic hematopoietic
      stem cell transplantation.
AB  - BACKGROUND: Influenza can cause significant morbidity and mortality in patients
      after hematopoietic stem cell transplantation (HSCT). The diagnostic methods and
      antiviral treatment have scarcely been investigated. METHODS: We retrospectively
      identified influenza-infected patients with upper or lower respiratory tract
      infection (RTI) diagnosed by culture and polymerase chain reaction (PCR) testing
      between November 2007 and April 2008. Treatment with oseltamivir 75 mg twice
      daily and serial nasal swabs were performed at the discretion of the treating
      physician. RESULTS: We identified 21 influenza infections in 19 patients: 19 with
      upper RTI and 2 with lower RTI. At diagnosis, all 21 samples were positive for
      PCR with a median influenza load of 5.9 log(10) copies/mL. Culture was positive
      in 14 (67%) patients. Influenza A virus was diagnosed in 8 (38%) episodes and
      influenza B virus in 13 (62%) episodes. Two patients were sequentially infected
      by influenza A, followed by B after 38 and 47 days, respectively. Eighteen (86%)
      patients were treated with oseltamivir for 11 days (median, interquartile range
      [IQR]: 8-14). No progression to lower RTI or mortality occurred. Shedding
      persisted for 12 days (median, IQR: 8-13). Absolute lymphocyte count at diagnosis
      correlated inversely with shedding of the virus (P<0.001). CONCLUSIONS:
      Oseltamivir is well tolerated and may reduce mortality of influenza virus
      infected patients after HSCT. PCR may help to optimize diagnosis and to monitor
      treatment strategies.

PMID- 19175541
TI  - Initial experience using continuous intravenous treprostinil to manage pulmonary
      arterial hypertension in patients with end-stage liver disease.
AB  - Treprostinil is a prostacyclin analog and has been used on idiopathic pulmonary
      arterial hypertension (PAH). There is only limited clinical experience using
      treprostinil to manage PAH in patients with end-stage liver disease (ESLD). We
      report three ESLD patients with PAH, who were treated with continuous intravenous
      treprostinil. A 59-year-old woman with ESLD secondary to alcoholic hepatitis had
      portopulmonary hypertension with mean pulmonary arterial pressure (mPAP) of 44
      mmHg and transpulmonary gradient (TPG) of 23 mmHg. Treprostinil at 45 ng/kg/min
      for 6 months decreased mPAP to 23 (TPG to 8). A 53-year-old man had ESLD
      secondary to alcoholic hepatitis with PAH caused by multiple pulmonary embolisms
      (mPAP of 32 and TPG of 23). Treprostinil at 36 ng/kg/min for 3 months decreased
      mPAP to 23 and TPG to 14. Both patients underwent uneventful liver
      transplantation. A 48-year-old man had ESLD secondary to hepatitis C and
      portopulmonary hypertension with mPAP of 60 and TPG of 44. Two years after
      intravenous treprostinil at 106 ng/kg/min, his mPAP decreased to 44 and TPG to
      30. These results demonstrate that for a selected group of ESLD patients with
      PAH, a continuous intravenous infusion of treprostinil appears to be safe and
      effective.

PMID- 19175542
TI  - Diabetic cheiroarthropathy following simultaneous pancreas-kidney
      transplantation.

PMID- 19175543
TI  - A meta-analysis of mini-open versus standard open and laparoscopic living donor
      nephrectomy.
AB  - Mini-open donor nephrectomy (MODN) potentially combines advantages of standard
      open (SODN) and laparoscopic techniques (LDN). This article is a comparison of
      these techniques. A literature search was performed for studies comparing MODN
      with SODN or LDN. Nine studies met our selection criteria. Of the 1038 patients,
      433 (42%) underwent MODN, 389 (37%) SODN and 216 (21%) LDN. MODN versus SODN:
      Operative time (P = 0.17), warm ischemia time (P = 0.20) and blood loss (P =
      0.30) were not significantly different. Hospital stay and time to return to work
      were shorter for MODN by 1.67 days (P < 0.001) and 5 weeks (P = 0.03). Analgesia
      requirement and overall complications were less in the MODN group (P < 0.001) and
      (P = 0.03). Ureteric complications (P = 0.21) and 1-year graft survival (P =
      0.28) were not significantly different. MODN versus LDN: Operative and warm
      ischemia times were significantly shorter for the MODN by 55 min (P = 0.005) and
      147 s (P < 0.001). Analgesia requirement was greater for the MODN group by 9.62
      mEq morphine (P = 0.04). No significant differences were found for blood loss (P
      = 0.8), hospital stay (P = 0.35), donor complications (P = 0.40) or ureteric
      complications (P = 0.83). MODN appears to provide advantages for the donor in
      comparison to SODN and also has a shorter operative time when compared with the
      LDN.

PMID- 19175544
TI  - A genetic strategy to control expression of human blood group antigens in red
      blood cells generated in vitro.
AB  - BACKGROUND: The ability to generate red blood cells of a chosen blood group
      phenotype would be a major advance in transfusion when considering low- and high
      frequency blood group antigens. STUDY DESIGN AND METHODS: Cord blood CD34+ cells
      undergoing erythroid differentiation in vitro were genetically manipulated with
      human immunodeficiency virus Type 1-derived lentiviral vectors expressing hUT-B1
      cDNA (overexpression strategy) or bicistronic vectors expressing both enhanced
      green fluorescent protein and a short-hairpin RNA (shRNA) designed to silence
      SLC14A1(JK) gene that encodes hUT-B1 protein (silencing strategy). Resulting cell
      populations were analyzed by fluorescent-activated cell sorting and gel affinity
      column assay. RESULTS: When transduced with hUT-B1 cDNA lentiviral vectors
      encoding JK*B and JK*A alleles, respectively, CD34+ cell-derived erythroid
      populations from Jk(a+b-) and Jk(a-b+) donors exhibited a Jk(a+b+) phenotype
      different from the original phenotype. In concomitant tests, Jk(a+b+) donor cells
      transduced with lentiviral vectors carrying a shRNA designed to interfere with
      hUT-B1 transcription showed a marked decrease in hUT-B1 expression and were
      assessed as null for Jk antigen by a routine assay. CONCLUSION: In this work
      focusing on the Kidd blood group system that relies on expression of hUT-B1
      glycoprotein under the Jk(a) or Jk(b) antigenic configurations, we demonstrated
      that hematopoietic progenitors could be genetically modified to exhibit a chosen
      Kidd phenotype. Beyond production of atypical Kidd phenotypes, this genetic
      strategy could allow generation of rare blood phenotypes from hematopoietic stem
      cells regardless of initial donor phenotype. Potential applications for
      genetically modified blood include production of control samples for
      immunohematologic testing and for resolution of antibody detection in multiply
      transfused patients.

PMID- 19175545
TI  - Assessment of safety in neonates for transfusion of platelets and plasma prepared
      with amotosalen photochemical pathogen inactivation treatment by a 1-month
      intravenous toxicity study in neonatal rats.
AB  - BACKGROUND: It is estimated that approximately 300,000 neonates undergo
      transfusions annually. The neonatal immune system is immature, making such
      patients more susceptible to the effects associated with transfusion-transmitted
      bacteria, viruses, protozoa, and white blood cells (WBCs). The INTERCEPT Blood
      System is a photochemical process (PCT) utilizing amotosalen and long-wavelength
      ultraviolet to inactivate pathogens and WBCs in both platelet (PLT) and plasma
      components for transfusion. A series of clinical studies has shown PCT PLTs and
      PCT plasma to be safe and effective for transfusion in adults and pediatric
      patients. Because clinical studies in neonates are technically difficult and
      ethically challenging, preclinical toxicologic studies were conducted in neonatal
      rats to evaluate the safety of PCT blood components for neonates. STUDY DESIGN
      AND METHODS: This study examined daily intravenous administration to neonatal
      rats of amotosalen in 35 percent:65 percent plasma:InterSol from 1 microg per kg
      per day (representing 1-unit transfusion) to 457 microg per kg per day
      (representing multiple transfusions) from Postnatal Day 4 (PND4) to PND31. Rats
      were observed for viability, clinical signs, and body weights until PND31 and
      then subjected to pathology evaluation. Hematology, clinical chemistry, and
      urinalysis data were also collected on PND31. Toxicokinetic parameters were
      evaluated on PND4 and PND31. RESULTS: There were no amotosalen-related effects on
      clinical signs, body weight, hematology, clinical chemistry, urinalysis, gross
      pathology, or histopathology, despite the exposure of neonatal rats to amotosalen
      concentrations as high as approximately 48 times the standard exposure in adult
      patients. CONCLUSION: This study demonstrates the safety of PCT for transfusion
      in neonatal rats and augments data from other studies and clinical use supporting
      the use of PCT in neonatal patients.

PMID- 19175546
TI  - Very high users of platelet transfusions in the neonatal intensive care unit.
AB  - BACKGROUND: In neonatal intensive care unit (NICU) practice, a small percentage
      of the patients receive a large proportion of the platelet (PLT) transfusions
      administered. This study sought to better define this very-high-user group. To
      accomplish this, records of all NICU patients in a multihospital health care
      system who, during a recent 5(1/2)-year period, received 20 or more PLT
      transfusions were examined. STUDY DESIGN AND METHODS: Electronic medical record
      repositories of Intermountain Healthcare neonates with dates of birth from
      January 1, 2002, through June 30, 2007, who received 20 or more PLT transfusions
      were identified. The causes of the thrombocytopenia were sought, whether each
      transfusion given was a treatment for bleeding versus prophylaxis was determined,
      whether each transfusion was compliant with our transfusion guidelines was
      judged, and the outcomes were tabulated. RESULTS: During this period, 45 patients
      received 20 or more PLT transfusions (median, 29; range, 20-79). Medical
      conditions could be categorized into six diagnoses: 1) extracorporeal membrane
      oxygenation (ECMO) for congenital diaphragmatic hernia (CDH; n = 13), 2) fungal
      sepsis (n = 8), 3) ECMO for reasons other than CDH (n = 8), 4) necrotizing
      enterocolitis (n = 7), 5) bacterial sepsis (n = 7), and 6) congenital
      hyporegenerative thrombocytopenia (n = 2). Nineteen percent of the transfusions
      were ordered for oozing, bruising, or bleeding and 81 percent for prophylaxis.
      Thirty-six percent of transfusions were given in violation of our transfusion
      guidelines. Forty-nine percent of the high users died, but no deaths were due to
      hemorrhage. All survivors developed chronic lung disease, and all survivors
      weighing less than 1250 g at birth developed retinopathy of prematurity.
      CONCLUSIONS: Almost all patients that received 20 or more PLT transfusions had an
      acquired, consumptive thrombocytopenia. All could have received fewer
      transfusions had the guidelines already in place been observed. Eighty-one
      percent fewer PLT transfusions would have been administered had the paradigm been
      transfusing only if oozing, bruising, or bleeding was present.

PMID- 19175547
TI  - P-selectin mRNA is maintained in platelet concentrates stored at 4 degrees C.
AB  - BACKGROUND: Platelets (PLTs) contain mRNA and synthesize proteins in response to
      activation. Most guidelines for PLT concentrates (PCs) recommend ambient
      temperature for storage but the impact of the storage temperature on PLT mRNA
      content has not yet been investigated. STUDY DESIGN AND METHODS: Ten leukoreduced
      apheresis PCs were split and stored at 22 and 4 degrees C. P-selectin mRNA, its
      expression on PLTs, and its soluble form were quantified. In parallel, cellular
      (cell count, mean PLT volume), metabolic (pH, pO(2), pCO(2), HCO(3), glucose),
      and functional markers (swirling, hypotonic shock response, aggregation to
      collagen) were analyzed. Rotation thrombelastography was used to monitor the
      hemostatic potential of PLTs. All measurements were performed on Days 1 and 5 of
      storage. RESULTS: After 5 days of storage at 4 degrees C, only 31 +/- 27 percent
      of P-selectin mRNA and 29 +/- 41 percent of glyceraldehyde-3-phosphate
      dehydrogenase mRNA were lost, while minute amounts of the mRNAs were detectable
      at 22 degrees C. In PCs stored at 4 degrees C the percentage of P-selectin
      positive PLTs was significantly higher when compared to PCs stored at 22 degrees
      C. Soluble P-selectin concentrations did not significantly differ between both
      storage temperatures. Thrombelastography revealed significantly shorter reaction
      times in PLTs kept at 4 degrees C. CONCLUSION: Our data indicate that storage at
      4 degrees C is accompanied by maintained mRNA levels. PLTs with intact mRNA
      levels and short reaction times in thrombelastography might be functionally
      superior to PLTs that are devoid of mRNA and show less augmented P-selectin
      surface expression. In therapeutic applications, that is, if PLTs are transfused
      to control acute bleeding, PLTs kept at 4 degrees C may be advantageous.

PMID- 19175548
TI  - Impact of limiting erythropoiesis-stimulating agent use for chemotherapy-induced
      anemia on the United States blood supply margin.
AB  - BACKGROUND: Recently, the Centers for Medicare and Medicaid Services issued a
      national coverage determination that limited erythropoiesis-stimulating agents
      (ESAs) utilization in patients with chemotherapy-induced anemia (CIA). This study
      evaluated the impact of limiting the use of ESAs for CIA on the US blood supply
      margin. STUDY DESIGN AND METHODS: A modeling simulation was employed to compare
      the number of red blood cell (RBC) units transfused in CIA patients treated with
      ESAs to the number of RBC units that would be transfused if ESAs were limited or
      discontinued. The excess number of RBC units that would be required with limited
      ESA treatment was contrasted with the available marginal blood supply from 2004
      and 2008. Model inputs were obtained from published literature or empirical
      evidence when published information was unavailable. RESULTS: The model predicted
      that up to 18 and 15 percent of the respective 2004 and 2008 marginal US blood
      supply would be required to cover the incremental demand for blood that would
      arise from a 25 percent decrease in ESA use. For ESA use reductions of 50 and 75
      percent, the model predicted 17 to 21 percent (134,667 units) and 26 to 31
      percent (202,001 units) of the 2008 and 2004 marginal US blood supply would be
      required, respectively. CONCLUSION: This study showed that limiting ESA use in
      CIA patients would impose considerable pressure on the available blood supply
      margin given the small margin between usable blood and transfusion demand. The
      public health consequences of such an outcome should be taken into account when
      revisions to ESA use are being considered.

PMID- 19175549
TI  - Genetic variation of FUT3 in Ghanaians, Caucasians, and Mongolians.
AB  - BACKGROUND: The FUT3 gene regulates the expression of Lewis blood group antigens.
      Several lines of evidence suggest association between expression of these
      antigens and Helicobacter pylori infection or susceptibility to cardiovascular
      diseases. Single-nucleotide polymorphisms (SNPs) responsible for the Lewis
      negative phenotype have been reported, but systematic sequence analyses have not
      yet been performed. STUDY DESIGN AND METHODS: The polymerase chain reaction
      product containing the whole FUT3 coding region (1086 bp) was sequenced in three
      human populations, Ghanaians (n = 106), Caucasians (n = 100), and Mongolians (n =
      50). Some haplotypes were determined by sequencing cloned inserts, and the other
      haplotypes were inferred by the free software program PHASE. Also examined was
      the functional significance of several newly identified SNPs by a transient
      expression study. RESULTS: Thirty-two SNPs were found, including 15 novel SNPs,
      in the three populations. The functional impact of three nonsynonymous SNPs that
      occurred on the Lewis-positive alleles or weakly enzyme-inactivating alleles was
      examined. A transient expression study suggested that 478C>T and 968G>C are
      enzyme-inactivating mutations. CONCLUSION: Sequence analysis identified many
      SNPs, but most of them are in complete linkage disequilibrium with previously
      reported SNPs responsible for the Lewis-negative phenotype. 13G>A, 59T>G, and
      202T>C seem to be useful as tag SNPs for detection of Lewis-negative alleles in
      genotyping of Lewis blood groups and large-scale association studies with
      diseases in many populations.

PMID- 19175550
TI  - Pictorial representation of transfusion over the years.
AB  - BACKGROUND: The writings of the 17th and 19th centuries about experiments and
      debates about transfusion were often analyzed and discussed in articles and
      books, but an analysis of illustrations of transfusion during this pioneering
      epoch can throw new light on the subject. The first transfusion attempts were as
      sensational as they were spectacular, and their illustration permitted both
      focusing attention and giving a scientific iconography, almost technical, to
      doctors and scholars of the time. STUDY DESIGN AND METHODS: We describe several
      illustrations of historical transfusions and point out common characteristics and
      differences, through the major elements used by illustrators. RESULTS: Nineteen
      illustrations are shown and commented upon. The transfusion imagery, through the
      representation of the three actors of transfusion (recipient, donor, doctor)
      varied considerably over time, as did representation of the procedures of
      transfusion. CONCLUSION: This series of illustrations over three centuries
      reveals what the use and function of picturing transfusion over the course of
      time were: on the one hand, a didactic intent, in offering a documentary source
      concerning procedures and necessary instruments, and on the other, the function
      of legitimization, representing the act with a subtext such as numbered titles or
      in a scientific article, brought transfusion into the category of technical
      practices that were regulated by rules.

PMID- 19175551
TI  - Effects of applied muscle tension on the likelihood of blood donor return.
AB  - BACKGROUND: Blood donation-related symptoms such as dizziness and fainting are
      unpleasant for the donor and a significant disincentive for repeat donation. The
      muscle tensing technique of applied muscle tension reduced symptoms in several
      studies. STUDY DESIGN AND METHODS: Follow-up data from a randomized controlled
      trial of different components of applied tension were obtained. The number of
      subsequent blood donations in a 2-year period was determined for 1059 of 1209
      donors originally assigned to one of six conditions involving tension of
      different muscle groups or donation as usual. RESULTS: In general, women who were
      assigned to one of the applied tension conditions were significantly more likely
      to return than women assigned to the donation as usual condition (67% vs. 55%,
      chi(2)(1) = 4.71, p = 0.03). There was no significant enhancement of return among
      male donors. Also, there was no association between the actual reduction of
      symptoms in different applied tension conditions and higher levels of return.
      CONCLUSION: Participation in a condition that involved learning repeated muscle
      tension with the expectation that this might help reduce blood donation-related
      symptoms was associated with a greater likelihood of return for women.

PMID- 19175552
TI  - Characterization of anti-D monoclonal antibody reagents based on their reactivity
      with the weak D phenotype.
AB  - BACKGROUND: Anti-D monoclonal antibody (MoAb) reagents have improved D typing in
      routine tests. However, they exhibit a wide range of reactivity with the weak D
      phenotype depending on the characteristics of the different MoAbs used. We
      analyzed the reactivity of immunoglobulin (IgM) anti-D by cluster analysis to
      characterize MoAb that have similar reactivities with the weak D phenotype. STUDY
      DESIGN AND METHODS: We used 36 consecutive samples with weak D phenotype in
      routine testing and determined their reactivity with different IgM and IgG anti-D
      MoAbs. The samples were characterized as belonging to a weak D type or category
      using commercial molecular biology kits. RESULTS: The various anti-D MoAbs showed
      a wide grade of reactivity with the weak D samples. Similarities and
      dissimilarities in the behavior of the anti-D MoAbs with the weak D phenotype
      samples were detected with cluster analysis and the multidimensional scaling
      analysis. These analyses indicated different families of MoAbs characterized as
      having a high degree of homogeneity in their reactivity with the weak D
      phenotype. Between these MoAb families, the most effective at reacting with the
      weak D phenotype were RUM-1 and 175-2. CONCLUSIONS: The results show that it is
      possible to classify the anti-D MoAbs on the basis of their reactivity with the
      weak D phenotype. This provides information about different MoAbs' properties on
      the basis of their belonging to a given of anti-D family.

PMID- 19175553
TI  - Low-avidity HPA-1a alloantibodies in severe neonatal alloimmune thrombocytopenia
      are detectable with surface plasmon resonance technology.
AB  - BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is mostly
      caused by maternal alloantibodies directed against the human platelet alloantigen
      (HPA)-1a. Currently, the serologic diagnosis of FNAIT is based on the
      characterization of the HPA alloantibodies in monoclonal antibody-based antigen
      capture assays (e.g., MAIPA assay). Accumulated current evidence indicated that
      such assays may overlook some HPA-1a antibodies. STUDY DESIGN AND METHODS: This
      study employed surface plasmon resonance (SPR) technology using immunoaffinity
      purified glycoprotein IIb/IIIa isoforms immobilized on biosensor chips to study
      the binding kinetics of HPA-1a alloantibodies from different FNAIT cases in real
      time. RESULTS: Analysis of HPA-1a alloantibodies from FNAIT cases (n = 9) in SPR
      showed a moderate relative response (22.2-69.7 resonance units [RU]) and slow
      antibody dissociation. After the dissociation phase, varying amounts of bound
      antibodies (41%-79%) remained on the chip. In contrast in HPA-1a alloantibodies
      from a patient suffering from posttransfusion purpura, a high relative response
      (approximately 490 RU) was observed at the end of the association phase and no
      dissociation of antibody binding was detectable. Of particular relevance, by the
      use of this SPR technique, HPA-1a alloantibodies were detected in two severe
      FNAIT cases that had determined as false negative by MAIPA assay. In SPR, these
      HPA-1a alloantibodies showed low-avidity nature characterized by gradual
      dissociation of antibody during the association phase and complete detachment of
      antibody binding after the dissociation phase. This high "off-rate" character of
      low-avidity HPA-1a alloantibodies indicates that such antibody binding is easily
      detachable by the extensive washing procedure of the MAIPA. CONCLUSIONS: Our
      results demonstrated that the SPR method can facilitate the diagnosis of
      clinically relevant low-avidity HPA-1a antibodies.

PMID- 19175554
TI  - Human platelet antigen typing of neonatal alloimmune thrombocytopenia patients
      using whole genome amplified DNA and a 5'-nuclease assay.
AB  - BACKGROUND: A serious constraint in the investigation of the human platelet
      antigen (HPA) status of potential neonatal alloimmune thrombocytopenia (NAIT)
      cases is the limited amount of DNA available from the neonates. Whole genome
      amplification (WGA) of these DNA samples could overcome this problem, but
      requires validation to ensure that it is sufficiently sensitive and accurate
      before its application in a clinical diagnostic setting. STUDY DESIGN AND
      METHODS: This study has validated the use of WGA DNA for HPA-1, -2, -3, -4, -5,
      and -15 genotyping with a panel of six controls and 13 previously HPA-typed
      samples from neonates together with parental DNA, using a 5'-nuclease (TaqMan)
      assay. WGA was performed using titrated amounts of genomic and WGA DNA template.
      HPA typing was performed on genomic and amplified DNA using a 5'-nuclease assay
      or polymerase chain reaction with sequence-specific primers (PCR-SSP). RESULTS:
      WGA DNA yields were in the suggested range of 400x to 800x, as assessed by
      spectrophotometry and gel analysis, and did not require further purification. HPA
      genotyping showed 100 percent concordance when using down to 5 ng of genomic or
      WGA template. CONCLUSION: This study demonstrates that WGA can be used for HPA
      typing using PCR-SSP or plate-based 5'-nuclease assays. The use of WGA for HPA
      typing in clinical samples from NAIT patients was validated with 100 percent
      concordance, and it is suggested that this technology can be used for other
      analyses where DNA amounts are limited.

PMID- 19175555
TI  - Blood donor deferral in Minas Gerais State, Brazil: blood centers as sentinels of
      urban population health.
AB  - BACKGROUND: Shortage of safe blood donors is frequent and it is important to
      understand the causes of deferral of potential donors, who reside mainly in urban
      areas, to improve recruitment campaigns aiming at the quality/availability of
      donors. STUDY DESIGN AND METHODS: In Minas Gerais State, Brazil, Hemominas
      Foundation collects, analyzes, and distributes more than 90 percent of blood.
      Blood is collected in 19 centers in cities. In 2006, data from 335,109 attempts
      to donate were analyzed. RESULTS: Seventy-seven percent of donor candidates were
      less than 40 years old, with 57.1 percent nonwhite and 66 percent male. A total
      of 21.6 percent were deferred at the interview. Women were more clinically
      deferred than men (25.5% vs. 19.6%). In larger cities, the proportion of first
      time donors (FTs) was higher (67.8%). The main causes of permanent deferral among
      FTs were neurologic diseases (37.5%), chronic hypertension (22.2%), and
      endocrinologic diseases (9.9%). The main causes of temporary clinical deferral in
      this group were risky behavior for sexually transmitted diseases (32.6%), anemia
      (8.5%), and hypertension (6%). The main causes of permanent deferral in repeat
      donors (RTs) were chronic hypertension (31.6%) and neurologic diseases (22.1%);
      for temporary deferral it was anemia (22.6%). A total of 2.9% of the collected
      blood bags were discarded due to reactive tests (FTs = 34.82/1000; RTs =
      3.51/1000). CONCLUSION: A deferral study in blood donor candidates may shed light
      on regional diversity, highlighting how social inequalities and health status of
      the general population may affect the blood supply. Risk factors and marker rates
      derived from the donor pool may be useful to gain insights regarding public
      health issues.

PMID- 19175556
TI  - Failure of IL-8 to assess early reperfusion injury following lung transplantation
      of cardiac death donor pigs.
AB  - Although interleukins (IL) 8 and 10 predict lung viability in lung
      transplantation from heart beating donors (HBD) and IL-1beta is a marker of ex
      vivo performance from after cardiac death donors (ACDD), IL expression in the
      recipient remains unknown. This study assessed IL-1beta, IL-8 and IL-10 as
      indicators of functional performance in single-lung transplantation from ACDD
      pigs. Animals were divided into: (i) HBD: immediate lung excision; (ii) ACDD:
      fibrillation, 30 min warm ischemia and 3 h topical cooling. Left lungs of both
      groups were then flushed with Perfadex and stored at 3-4 degrees C for 3 h. IL in
      bronchoalveolar lavage fluid (BAL) and hemodynamic and graft function were
      measured in the donor and during the 2 h reperfusion period in the recipient.
      Myeloperoxidase, nuclear factor kappa beta, wet/dry weight ratio and a histologic
      injury score were assessed from biopsies in basal conditions in the donor and at
      the end of reperfusion. Despite similar pulmonary function and histologic markers
      of injury in both groups and higher IL-1beta in the donor of ACDD, IL-8 during
      reperfusion was significantly lower in ACDD (119 +/- 33% of basal) than in HBD
      (306 +/- 238%, P < 0.05) recipients. The paradoxical behavior of IL-8 makes it an
      unreliable predictor of ACDD early outcome in this transplantation model.

PMID- 19175557
TI  - Nocardia niigatensis infection in a kidney transplant recipient.
AB  - This is the first reported case of Nocardia niigatensis infection in an adult
      kidney transplant recipient. A 57-year-old Asian woman presented with multiple
      cutaneous abscesses and rapidly growing fungating mass on the left pretibial area
      for 2 months. She received a cadaveric kidney transplant 4 years previously and
      was undergoing immunosuppression with prednisolone, cyclosporine and
      mycophenolate sodium. The microbiological diagnosis was established by isolation
      of Nocardia from the purulent material expressed from a granule. The strain was
      identified to the species level by 16S rRNA gene-targeted PCR. The closest match
      was with N. niigatensis. Antibiotic treatment (trimethotrim-sulfamethoxazole) was
      continued for 6 months and the skin lesions improved.

PMID- 19175558
TI  - Successful treatment of invasive sphenoidal, pulmonary and intracerebral
      aspergillosis after multivisceral transplantation.

PMID- 19175559
TI  - Noncognate function of B cells in transplantation.
AB  - How B cells affect the outcome of transplants is a question of enduring interest.
      Initial efforts to answer that question suggested, wrongly, that B cells have no
      impact on transplantation. Now, however, B cells are known to influence not only
      the outcome of vascularized grafts through the production of anti-donor
      antibodies but also the competence of cellular immunity through a number of
      physiologic functions. In this study, we explain why the importance of B cells
      was overlooked in the past and consider the range of noncognate functions of B
      cells that may determine the outcome of transplants.

PMID- 19175560
TI  - Medication-taking among adult renal transplant recipients: barriers and
      strategies.
AB  - Medication adherence is essential for the survival of kidney grafts, however, the
      complexity of the medication-taking regimen makes adherence difficult. Little is
      known about barriers to medication-taking and strategies to foster medication
      taking. This cross-sectional study involved semi-structured interviews with 82
      kidney transplant recipients approximately 2 months post-transplant on medication
      related adherence, barriers to medication-taking, and strategies to foster
      medication-taking. Although self-reported adherence was high (88%), qualitative
      analysis revealed that half of the patients (49%) reported experiencing at least
      one barrier to medication-taking. The most common barriers were: not remembering
      to refill prescriptions (13%), changes to medication prescriptions or dosages
      (13%), being busy (10%), forgetting to bring medicines with them (10%), and being
      away from home (10%). The most common strategies to foster medication-taking
      were: maintaining a schedule of medication-taking (60%), organizing pills using
      pillboxes, baggies, cups (42%), bringing medicines with them (34%), organizing
      pills according to routine times (32%), and relying on other people to remind
      them (26%). Understanding the range of barriers to adherence and strategies
      kidney recipients devised to promote medication-taking may help transplant
      clinicians to better educate transplant recipients about appropriate medication
      taking, mitigate the risk of medication nonadherence-related rejection, and may
      help inform patient-centered interventions to improve medication adherence.

PMID- 19175561
TI  - False aneurysm of a hepatic artery branch complicating intrahepatic islet
      transplantation.
AB  - Islet transplantation, an innovative treatment strategy for type 1 diabetes
      mellitus, is a relatively safe procedure, with less morbidity than pancreas
      transplantation. Vascular injuries have not been reported to date. We report a
      percutaneous transhepatic intraportal islet transplant infusion that was followed
      by bleeding from a false aneurysm of an intrahepatic branch of the hepatic
      artery. The bleeding was controlled by selective embolization. Despite the
      complication and its treatment, the patient gained insulin independence, which
      was sustained for 285 days. She is currently on a small dose of insulin with good
      glycemic control.

PMID- 19175562
TI  - Pegylated interferon-alpha-based treatment for chronic hepatitis C in renal
      transplant recipients: an open pilot study.
AB  - Treatment of hepatitis C in renal transplant recipients remains a controversial
      issue, as interferon therapy has been associated with a high risk of rejection
      and poor efficacy. We report here the use of pegylated interferon-alpha, alone or
      in combination with ribavirin, in renal transplant recipients with chronic
      hepatitis C. Eight renal transplant recipients with chronic hepatitis C were
      recruited. The mean delay between renal transplantation and antiviral therapy was
      198.8 months. Sustained virological response was observed in four of out eight
      patients. Three patients with sustained virological response were genotype 2, one
      was genotype 1; fibrosis stages were F1 for one patient, F2 for 2, F3 for one. At
      baseline, renal dysfunction was moderate in seven patients and severe in one
      patient. No patient experienced rejection episodes during or after pegylated
      interferon-alpha therapy. One patient developed haemolytic uraemic syndrome,
      which eventually resulted in graft loss and return to dialysis. In conclusion,
      for renal transplant recipients treated with pegylated interferon-alpha-based
      therapy, we observed a low risk of renal dysfunction, acceptable tolerance and
      significant virological efficacy. This is therefore the first study to suggest
      that pegylated interferon-alpha could be proposed late after transplantation to
      renal transplant recipients.

PMID- 19175563
TI  - Is it possible to predict the early post-transplant allograft function using 20
      HETE measurements? A preliminary report.
AB  - 20-HydroxyEicosaTetraEnoic (20-HETE) acid is an arachidonic acid metabolite that
      is generated via cytochrome P450 enzymes, and according to the findings from
      recent studies, may be involved in the pathogenesis of ischemia-reperfusion
      injury. The aim of this study was to: examine the dynamics of 20-HETE changes
      during the first 5 min of allograft reperfusion, and analyze whether the observed
      changes are associated with post-transplant graft function. Sixty-nine renal
      transplant recipients were divided, according to their outcome, into early, slow
      and delayed graft function (EGF, SGF, DGF) group. Blood samples were collected
      directly before and during the first 5 min of allograft reperfusion. 20-HETE
      concentrations were measured using ELISA. The results demonstrated significant
      differences in the concentrations and in the dynamics of 20-HETE changes between
      patients with immediate graft function, and individuals with allograft activation
      problems. The sensitivity, specificity, positive and negative predictive value of
      20-HETEDelta(5-0) parameter in discriminating EGF and SGF from DGF were 69%, 54%,
      74% and 48% respectively. Therefore, our results demonstrated that the dynamics
      of 20-HETE changes, which occurs during early phase of allograft reperfusion, is
      associated with early post-transplant graft function and also highlighted 20-HETE
      as a novel clinical marker of post-transplant allograft function.

PMID- 19175564
TI  - Recombinant human hepatitis B vaccine initiating alopecia areata: testing the
      hypothesis using the C3H/HeJ mouse model.
AB  - Untoward effects of human vaccines suggest that recombinant hepatitis B vaccine
      may induce alopecia areata (AA) in some patients. Similar untoward immunological
      effects may also account for AA-like diseases in domestic species. In this study,
      the C3H/HeJ spontaneous adult onset AA mouse model was used to test the role, if
      any, of recombinant hepatitis B vaccine on the initiation or activation of AA.
      Initial experiments demonstrated no effect on induction of AA in young adult
      female C3H/HeJ mice (P = 0.5689). By contrast, older females, those at the age
      when AA first begins to appear in this strain, had a significant increase (P =
      0.0264) in the time of onset of AA, suggesting that the vaccine may initiate
      disease in mice predisposed to AA. However, larger vaccine trials, which included
      diphtheria and tetanus toxoids as additional controls, did not support these
      initial result findings and suggest that AA associated with vaccination may be
      within the normal background levels of the given population.

PMID- 19175565
TI  - Establishment of a cell line expressing recombinant factor VII and its subsequent
      conversion to active form FVIIa through hepsin by genetic engineering method.
AB  - BACKGROUND: Factor VII (FVII) is a plasma glycoprotein that participates in the
      coagulation process leading to generation of fibrin. It is converted to factor
      VIIa that plays an important role in the coagulation cascade. The aim of this
      study was isolating and cloning the genes of human factor VII and hepsin and
      subsequent co-transfection of the constructs to Chinese hamster ovary (CHO) cell
      line to obtain rFVIIa. METHODS: Factor VII and hepsin cDNAs were isolated from
      HepG2 cell line and cloned into pcDNA3.1 (+) vector. The constructs were co
      transfected to CHO cell line. A cell line that permanently expressed recombinant
      factor VII (rFVII) and hepsin was established. The expression of rFVII was
      confirmed by reverse transcriptase-polymerase chain reaction, enzyme-linked
      immunosorbent assay and Western blot analysis. Biological activity of rFVII was
      evaluated by prothrombin time assay. RESULTS: The results showed that the genes
      of FVII and hepsin were successfully cloned and expressed. Stable CHO cells co
      transfected with pcNDA3.1-FVII and pcNDA3.1-hepsin expressed FVII and hepsin
      mRNA, but there was no expression in the CHO cells transfected with insert free
      pcDNA3.1. FVIIa protein was secreted to medium of CHO cells co-transfected with
      pcNDA3.1-FVII and pcNDA3.1-hepsin. The expected band of rFVII was detected in
      Western blot analysis. A three- to fourfold decrease in clotting time was
      observed when human FVII-depleted plasma was used in combination with human
      thromboplastin in the presence of rFVII, confirming the biological activity of
      rFVII. CONCLUSION: As we are aware, this is the first report of establishing a
      cell line expressing FVIIa using genetic engineering methods.

PMID- 19175566
TI  - Microparticle sizing by dynamic light scattering in fresh-frozen plasma.
AB  - BACKGROUND: We have previously shown that fresh-frozen plasma (FFP) contains red
      blood cell-derived procoagulant microparticles (MPs) that are removable by 0.2
      microm filtration. Given the limitations of current methods for accurately sizing
      MPs, we have applied the novel approach of dynamic light scattering (DLS) to
      characterize the size distributions of these MPs within FFP. METHODS: Fresh
      frozen plasma was prepared from blood Group A and O donations (n = 10 of each)
      after an overnight hold of whole blood at 4 degrees C. On the day of analysis,
      plasma was thawed to 37 degrees C and daughter aliquots were studied pre- and
      post-filtration (0.2 microm filtration device, Ceveron MFU-500, Technoclone). MP
      size and dispersity was assessed using a Zetasizer Nano S (Malvern Instruments
      Ltd), which employs a 173 degrees backscatter detector and an N5 Submicron
      Particle Size Analyser (Beckman Coulter) using multi-angle measurements (30.1
      degrees , 62.6 degrees and 90 degrees ). The analysers presented MP size
      distribution graphically as intensity plots, mean size, standard deviation and
      polydispersity index. RESULTS: Of the instruments used, only the N5 utilizing a
      30.1 degrees angle of measurement could detect MPs of the expected size
      distribution and demonstrate their removal by filtration. MPs (range of mean
      particle diameters: pre, 101-464 nm; post, 21-182 nm filtration) were
      significantly smaller post-filtration (P < 0.0001), but polydispersity index
      (median: pre, 0.746, post, 0.769) exhibited no significant change. There was no
      significant difference between the size of MPs from blood Group O (pre, 247 nm)
      and Group A (pre, 289 nm) samples (P = 0.44). CONCLUSION: Our data demonstrates
      that DLS offers a novel approach to assessing MP size and distribution, a
      technique that could be easily adopted as a means of assessing MPs within either
      FFP or other blood products.

PMID- 19175567
TI  - Human cystic echinococcosis in Yasuj District in Southwest of Iran: an
      epidemiological study of seroprevalence and surgical cases over a ten-year
      period.
AB  - Cystic echinococcosis is a zoonotic infection of humans and domestic animals
      caused by the larval stages of the cestode Echinococcus granulosus. Cystic
      echinococcosis is one of the most important zoonotic diseases in Iran, where
      human cases are frequently reported from different regions of the country. The
      objective of this study was to determine the sero-epidemiological and surgical
      cases of human hydatidosis in the Yasuj district, a region in southwest of Iran.
      Serum samples were taken from 500 individuals attending Yasuj health centers.
      Anti-hydatid cyst antibody was checked by enzyme-linked immunosorbent assay
      (ELISA), using antigen B. Moreover, retrospective studies were carried out using
      local hospital records of CE patients between 1997 and 2006. Results of the sero
      epidemiological study showed that 36 out of 500 cases (7.2%) have antibody
      against hydatid cyst. Of these 36 cases, 49.6% were women and 50.4% were men. The
      highest rate of infection was recorded in individuals aged between 30 and 39
      years. Hospital records showed that during the 10 years, 105 cases of hydatidosis
      were admitted in Yasuj hospitals. Of all cases, 70 (66.7%) were women and 35
      (33.3%) were men. Hepatic cyst was recorded in 81% of the cases where nephrotic
      cysts were the second most prevalent ones. Recurrence of the disease was noted in
      14.3% of all cases. Results of this study demonstrated that hydatidosis is an
      important endemic disease, with a nearly constant prevalence rate during the last
      10 years, in Yasuj district in Iran. Further studies are needed to investigate
      the reasons for high rate of surgical cases in housewives and striking prevalence
      of hydatidosis in a specific (30-40 years) age group.

PMID- 19175569
TI  - Vaccination with Mycobacterium bovis BCG strains Danish and Pasteur in white
      tailed deer (Odocoileus virginianus) experimentally challenged with Mycobacterium
      bovis.
AB  - Wildlife reservoirs of Mycobacterium bovis represent serious obstacles to the
      eradication of tuberculosis in domestic livestock and the cause for many
      faltering bovine tuberculosis eradication programmes. One approach in dealing
      with wildlife reservoirs of disease is to interrupt inter-species and
      intraspecies transmission through vaccination of deer or cattle. To evaluate the
      efficacy of BCG vaccination in white-tailed deer, 35 deer were assigned to one of
      three groups; one s.c. dose of 10(7) CFU of M. bovis BCG Pasteur (n = 12); 1 s.c.
      dose of 10(7) CFU of M. bovis BCG Danish (n = 11); or unvaccinated deer (n = 12).
      After vaccination, deer were inoculated intratonsilarly with virulent M. bovis.
      Lesion severity scores of the medial retropharyngeal lymph node, as well as all
      lymph nodes combined, were reduced in vaccinated deer compared to unvaccinated
      deer. BCG Danish vaccinated deer had no late stage granulomas characterized by
      coalescent caseonecrotic granulomas containing numerous acid-fast bacilli
      compared to BCG Pasteur vaccinated or unvaccinated deer where such lesions were
      present. Both BCG strains were isolated as late as 250 days after vaccination
      from deer that were vaccinated but not challenged. In white-tailed deer, BCG
      provides protection against challenge with virulent M. bovis. Issues related to
      vaccine persistence, safety and shedding remain to be further investigated.

PMID- 19175568
TI  - Direct detection of Mycobacterium bovis in bovine lymph nodes by PCR.
AB  - Thirty-five lymph node samples were taken from animals with macroscopic lesions
      consistent with Mycobacterium bovis infection. The animals were identified by
      postmortem examination in an abattoir in the northwestern region of state of
      Parana, Brazil. Twenty-two of the animals had previously been found to be
      tuberculin skin test positive. Tissue samples were decontaminated by Petroff's
      method and processed for acid-fast bacilli staining, culture in Stonebrink and
      Lowenstein-Jensen media and DNA extraction. Lymph node DNA samples were amplified
      by PCR in the absence and presence (inhibitor controls) of DNA extracted from M.
      bovis culture. Mycobacterium bovis was identified in 14 (42.4%) lymph node
      samples by both PCR and by culture. The frequency of PCR-positive results (54.5%)
      was similar to that of culture-positive results (51.5%, P > 0.05). The percentage
      of PCR-positive lymph nodes increased from 39.4% (13/33) to 54.5% (18/33) when
      samples that were initially PCR-negative were reanalysed using 2.5 microl DNA
      (two samples) and 1 : 2 diluted DNA (three samples). PCR sensitivity was affected
      by inhibitors and by the amount of DNA in the clinical samples. Our results
      indicate that direct detection of M. bovis in lymph nodes by PCR may be a fast
      and useful tool for bovine tuberculosis epidemic management in the region.

PMID- 19175570
TI  - Risk factors for encephalitis from West Nile Virus: a matched case-control study
      using hospitalized controls.
AB  - We conducted a case-control study to determine risk factors for developing
      encephalitis among West Nile virus cases when compared with age-, gender and
      race/ethnicity-matched hospitalized controls. In the multivariable conditional
      logistic regression analysis, we identified the following independent risk
      factors associated with being an encephalitis case: hypertension (OR 4.0; P =
      0.005), immunosuppressing conditions (OR 5.6; P = 0.001) and cardiovascular
      disease (OR = 28.3; P < 0.001). Individuals with these comorbidities should be
      targeted for education on protecting themselves from mosquito exposures.

PMID- 19175571
TI  - Serovars of Salmonella from captive reptiles.
AB  - The distribution on serovars of 60 Salmonella isolates from reptiles kept in
      captivity in Denmark during the period 1995-2006 was investigated. The isolates
      were all recovered from clinical specimens submitted to the National Veterinary
      Institute. A majority of the samples were from reptiles in zoological gardens or
      similar, while a minor number was from reptiles kept in private homes. A total of
      43 serovars were detected, most of them being what is usually called exotic
      serotypes, and many not having a trivial name, while a few isolates belonged to
      well-known human pathogenic serovars, such as S. Enteritidis, S. Typhimurium, S.
      Bovismorbificans. One isolate was rough and two were non-typeable. Isolates from
      turtles belonged to the subspecies enterica, while many isolates from both sauria
      and snakes belonged to other subspecies. The findings underline the potential
      zoonotic risk by handling reptiles in zoological garden or other public settings,
      or keeping pet reptiles in private homes.

PMID- 19175572
TI  - The methodological soundness of literature reviews addressing three potential
      zoonotic public health issues.
AB  - Literature reviews are important information sources for multiple stakeholders in
      zoonotic public health with limited time to keep up with the rapid increase in
      primary research in this field. However, their validity depends on their
      methodological soundness. The study purpose was to evaluate the methodological
      soundness of literature reviews in zoonotic public health. Relevant reviews (n =
      132) published between January 2000 and August 2006 were identified on three
      issues: Mycobacterium avium ssp paratuberculosis as a potential cause of Crohn's
      disease in humans (30 reviews); antimicrobial use in animals as a risk factor for
      antimicrobial resistance in human pathogens (36); and the zoonotic potential of
      transmissible spongiform encephalopathies (66). The zoonotic aspect of the issue
      was the focus of 59 reviews and a subsection of 73 reviews. Two independent
      reviewers evaluated reviews using 13 criteria: 10 previously validated in the
      medical field, and three applicable to aetiology research. No review met more
      than eight of 13 criteria for methodological soundness; two articles met only one
      criterion. Two reviews described methods for identifying relevant primary
      research. In only two and four reviews respectively, authors conducted
      quantitative syntheses of research evidence or reported summarized measures of
      effect for the zoonotic risk to humans. Recommendations for future research and
      economic impact were provided in 64 and 10 reviews respectively. In 14 reviews,
      conclusions exceeded evidence presented. The various review authors' position on
      the evidence for the zoonotic association and the zoonotic risk to public health
      were inconsistent for all three issues. Reviews addressing potential zoonotic
      public health issues lack structured and transparent methodology preventing the
      end user from assessing the review's validity. These reviews should adhere to
      structured scientific principles similar to what is used for primary research
      articles.

PMID- 19175573
TI  - A multi-level approach for investigating socio-economic and agricultural risk
      factors associated with rates of reported cases of Escherichia coli O157 in
      humans in Alberta, Canada.
AB  - Using negative binomial and multi-level Poisson models, the authors determined
      the statistical significance of agricultural and socio-economic risk factors for
      rates of reported disease associated with Escherichia coli O157 in census
      subdivisions (CSDs) in Alberta, Canada, 2000-2002. Variables relating to
      population stability, aboriginal composition of the CSDs, and the economic
      relationship between CSDs and urban centres were significant risk factors. The
      percentage of individuals living in low-income households was not a statistically
      significant risk factor for rates of disease. The statistical significance of
      cattle density, recorded at a higher geographical level, depended on the method
      used to correct for overdispersion, the number of levels included in the multi
      level models, and the choice of using all reported cases or only sporadic cases.
      Our results highlight the importance of local socio-economic risk factors in
      determining rates of disease associated with E. coli O157, but their relationship
      with individual risk factors requires further evaluation.

PMID- 19175574
TI  - Prevalence and risk factors for bacterial food-borne zoonotic hazards in
      slaughter pigs: a review.
AB  - The Hygiene Package and Regulation EC-2160/2003 require information flow from
      farm to slaughterhouse to enhance European consumers protection in a 'farm to
      fork' approach. This obligation especially concerns food-borne zoonotic hazards
      transmitted to humans through pork consumption, such as thermophilic
      Campylobacter spp., Listeria monocytogenes, Salmonella enterica and Yersinia
      enterocolitica. Prevalence estimates of these four hazards are affected by the
      sampling strategy and diagnostic procedure. Individual prevalence estimates for
      pig carriage (from digestive contents or lymph nodes collected at slaughterhouse)
      were higher than individual prevalence estimates for pig shedding (from faeces).
      Among risk factors described in the literature, poor pen cleaning and
      disinfection after pig departure to slaughterhouse and poor bio-security measures
      are of major significance. Moreover, whereas wet feed increases the risk of pig
      infection by L. monocytogenes, dry feed is a risk factor for Salm. enterica.
      Mixing batches of pigs, notably in fattening herds, represents a risk for the
      transmission of Salm. enterica and Y. enterocolitica. Whereas small herds are
      more infected by thermophilic campylobacters and Y. enterocolitica, higher
      prevalence of Salmonella is observed in large herds due to a more frequent mixing
      of batches. Antibiotic treatment during the finishing period increases the risk
      of transmission of Salm. enterica. The forenamed elements should be taken into
      account to characterize farms in a risk assessment approach and to improve
      zoonotic hazard management in the pork food chain.

PMID- 19175575
TI  - Monitoring pulmonary perfusion by electrical impedance tomography: an evaluation
      in a pig model.
AB  - BACKGROUND: Electrical impedance tomography (EIT) is a non-invasive technique
      that generates images of impedance distribution. Changes in the pulmonary content
      of air and blood are major determinants of thoracic impedance. This study was
      designed to evaluate EIT in monitoring pulmonary perfusion in a wide range of
      cardiac output. METHODS: Eight anaesthetised, mechanically ventilated pigs were
      fitted with a 16-electrode belt at the mid-thoracic level to generate EIT images
      that were analysed to determine pulse-synchronous systolic changes in impedance
      (DeltaZ(sys)). Stroke volume (SV) was derived using a pulmonary artery catheter.
      Reductions in cardiac pre-load, and thus pulmonary perfusion, were induced either
      by inflating the balloon of a Fogarty catheter positioned in the inferior caval
      vein or by increasing the positive end-expiratory pressure (PEEP). All
      measurements were performed in a steady state during a short apnoea. RESULTS:
      Pulse-synchronous changes in DeltaZ(sys) were easily discernable during apnoea.
      Balloon inflation reduced SV to 36% of the baseline, with a corresponding
      decrease in DeltaZ(sys) to 45% of baseline. PEEP reduced SV and DeltaZ(sys) to
      52% and 44% of the baseline, respectively. Significant correlations between SV
      and DeltaZ(sys) were demonstrated during all measurements (rho=0.62) as well as
      during balloon inflation (rho=0.73) and increased PEEP (rho=0.40). A Bland-Altman
      comparison of relative changes in SV and DeltaZ(sys) demonstrated a bias of -7%,
      with 95% limits of agreement at -51% and 36%. CONCLUSIONS: EIT provided beat-to
      beat approximations of pulmonary perfusion that significantly correlated to a
      wide range of SV values achieved during both extra and intrapulmonary
      interventions to change cardiac output.

PMID- 19175576
TI  - Platelet concentrates transfusion in cardiac surgery and platelet function
      assessment by multiple electrode aggregometry.
AB  - BACKGROUND: Platelet dysfunction contributes to the pathophysiology of bleeding
      complications during and after cardiac surgery. In most surgical institutions, no
      peri-operative point-of-care monitoring of platelet function is used. We
      evaluated the usefulness of the Multiplate platelet function analyser based on
      impedance aggregometry for identifying groups of patients at a high risk of
      transfusion of platelet concentrates (PC). METHODS: Platelet function parameters
      were determined in 60 patients before and after routine cardiac surgery.
      Impedance aggregometry measurements were performed on Multiplate using ADP
      (ADPtest), collagen (COLtest) and thrombin receptor activating peptide (TRAPtest)
      as platelet activators. The correlations between the aggregometry results and the
      transfusion of PC were calculated. The results of the aggregation tests were also
      divided into tertiles and the differences in PC transfusion between the low and
      the high tertile were assessed. RESULTS: Low aggregometry delimited groups of
      patients with significantly higher PC transfusion. In the receiver operating
      characteristic curve, low pre-operative aggregation in the ADPtest identified
      patients with high total transfusion of PC (area under the curve 0.74, P=0.001),
      while the ADPtest performed at the end of the operation identified patients with
      high PC transfusion on the intensive care unit (ICU) (area under the curve 0.76,
      P=0.002). CONCLUSIONS: Near-patient platelet aggregation may allow the
      identification of patients with enhanced risk of PC transfusion, both pre
      operatively and upon arrival on the ICU.

PMID- 19175577
TI  - Additives in intravenous anesthesia modulate pulmonary inflammation in a model of
      LPS-induced respiratory distress.
AB  - BACKGROUND: It has been suggested that propofol with ethylenediaminetetraacetic
      acid (EDTA) can modulate the systemic inflammatory response. Prolonged higher
      levels of pulmonary inflammation are associated with poor outcome of patients
      with acute lung injury. In the present study, we hypothesized that pulmonary
      inflammation could be modulated by propofol with EDTA compared with propofol with
      sulfite. METHODS: Respiratory distress was induced in rats (n=25) by
      intratracheal nebulization of lipopolysaccharide (LPS). After 24 h, animals were
      randomized to either propofol with EDTA (Propofol(EDTA)), propofol with sulfite
      (Propofol(sulfite)) or ketamine/midazolam (Ket/Mid); control animals received
      saline (n=30). Animals were ventilated for 4 h and blood gases were measured
      hourly. Bronchoalveolar lavage (BAL) was performed for cytokine analysis of:
      tumor necrosis factor (TNF), interleukin (IL)-6 and macrophage inflammatory
      protein (MIP)-2. RESULTS: LPS led to increased pulmonary inflammation in all
      groups compared with the control groups. Gas exchange deteriorated over time only
      in the LPS Propofol(sulfite) group and was significantly lower than the Ket/Mid
      group. Only IL-6 was significantly higher in the LPS Propofol(sulfite) group
      compared with both the Ket/Mid group and the Propofol(EDTA) group. CONCLUSION:
      Pulmonary IL-6 can be modulated by additives in systemic anesthesia. IMPLICATION
      STATEMENT: This study demonstrates that pulmonary inflammation caused by direct
      lung injury can be modulated by intravenous anesthesia used in critically ill
      patients.

PMID- 19175578
TI  - Beneficial effects of high positive end-expiratory pressure in lung respiratory
      mechanics during laparoscopic surgery.
AB  - BACKGROUND: The effect of neuromuscular blockade (NMB) and positive end
      expiratory pressure (PEEP) on the elastic properties of the respiratory system
      during pneumoperitoneum (PnP) remains a controversial subject. The main objective
      of the present study was to evaluate the effects of NMB and PEEP on respiratory
      mechanics. METHODS: We performed a dynamic analysis of respiratory mechanics in
      patients subjected to PnP. Twenty-one patients underwent cholecystectomy
      videolaparoscopy and total intravenous anesthesia. The respiratory system
      resistance (R(RS)), pulmonary elastance (E(P)), chest wall elastance (E(CW)), and
      respiratory system elastance (E(RS)) were computed via the least squares fit
      technique using an equation describing the motion of the respiratory system,
      which uses primary signs such as airway pressure, tidal volume, air flow, and
      esophageal pressures. Measurements were taken after tracheal intubation, PnP,
      NMB, establishment of PEEP (10 cmH2O), and PEEP withdrawal [zero end-expiratory
      pressure (ZEEP)]. RESULTS: PnP significantly increased E(RS) by 27%; both E(P)
      and E(CW) increased 21.3 and 64.1%, respectively (P < 0.001). NMB did not alter
      the respiratory mechanic properties. Setting PEEP reduced E(RS) by 8.6% (P <
      0.05), with a reduction of 10.9% in E(P) (P < 0.01) and a significant decline of
      15.7% in R(RS) (P < 0.05). These transitory changes in elastance disappeared
      after ZEEP. CONCLUSIONS: We concluded that the 10 cmH2O of PEEP attenuates the
      effects of PnP in respiratory mechanics, lowering R(RS), E(P), and E(RS). These
      effects may be useful in the ventilatory approach for patients experiencing a non
      physiological increase in IAP owing to PnP in laparoscopic procedures.

PMID- 19175579
TI  - The successful use of peripheral nerve blocks for femoral amputation.
AB  - We present a case report of four patients with severe cardiac insufficiency where
      peripheral nerve blocks guided by either nerve stimulation or ultrasonography
      were the sole anaesthetic for above-knee amputation. The patients were breathing
      spontaneously and remained haemodynamically stable during surgery. Thus, use of
      peripheral nerve blocks for femoral amputation in high-risk patients seems to be
      the technique of choice that can lower perioperative risk.

PMID- 19175582
TI  - Retraction: Interaction between a NMDA receptor antagonist, AP-5 and an AMPA
      receptor antagonist, YM 872 in antinociception in the spinal cord by Nishiyama T.

PMID- 19175584
TI  - Nasal intubation after tongue-flap surgery?

PMID- 19175585
TI  - Anaesthesia in patients with mastocytosis.

PMID- 19175586
TI  - Pre-operative hemodynamics in cardiac surgical patients: what do the numbers
      really mean?

PMID- 19175587
TI  - Children's day surgery: a challenge for the working team.

PMID- 19175588
TI  - Bilateral submandibular salivary gland swelling following regional anesthesia for
      hip replacement.

PMID- 19175589
TI  - Non-physician anaesthetists: should we still continue with the provision?

PMID- 19175591
TI  - Chronic urticaria: a patient survey on quality-of-life, treatment usage and
      doctor-patient relation.
AB  - BACKGROUND: Chronic urticaria (CU) is a common skin disorder characterized by
      recurrent spontaneous outbreaks of itchy wheals and/or angioedema. It has been
      shown to have substantial impact on patient quality-of-life, but little else is
      known about patient perspectives on CU and its treatment. METHODS: An internet
      survey was conducted with 321 randomly selected, representative adults in Germany
      and France who were diagnosed with CU. The survey included the Skindex-29
      questionnaire on quality-of-life and questions about treatment usage and
      patients' relation to their physician. Regression analyses were used to identify
      predictors of quality-of-life, use of prescription medication and various aspects
      of the doctor-patient relation. RESULTS: The survey confirmed that CU has
      substantial impact on quality-of-life, with median Skindex scores of 68 for
      symptoms, 50 for functioning and 53 for emotions. Only two in three respondents
      were taking prescription medication for their CU. Older respondents, French
      respondents and fully employed respondents were significantly (P < 0.01) more
      likely to be taking prescription medication. Only three in five respondents under
      a physician's care reported that their physician had discussed the emotional
      impact of CU on them. Patients whose physicians had discussed this emotional
      impact were significantly (P < 0.001) more satisfied with treatment and more
      trusting of their physician. CONCLUSIONS: CU has a heavy impact on quality-of
      life. Physicians need to be aware that many patients are not taking second
      generation anti-histamines and counsel them better on this point. Physicians
      should also discuss the emotional impact of CU with patients, because it improves
      their satisfaction and trust.

PMID- 19175592
TI  - Asthma and atopy are associated with chromosome 17q21 markers in Chinese
      children.
AB  - BACKGROUND: Single-nucleotide polymorphism (SNP)-based genome-wide association
      study revealed that markers on chromosome 17q21 were linked to childhood asthma
      but not atopy in Caucasians, with the strongest signal being detected for the SNP
      rs7216389 in the ORMDL3 gene. Such association was unknown in Chinese. This study
      delineated the allele and genotype frequencies of 10 SNPs at chromosome 17q21,
      and investigated the relationship between these SNPs and asthma and plasma IgE in
      southern Chinese children. METHODS: Asthmatic children and non-allergic controls
      were recruited from pediatric clinics. Their plasma total and aeroallergen
      specific IgE concentrations were measured by immunoassay. Ten SNPs on 17q21
      region were genotyped by multiplex SNaPshot, and their genotype associations with
      asthma traits analyzed using multivariate regression. RESULTS: 315 patients and
      192 controls were enrolled. The allele frequency for C allele of rs7216389 varied
      significantly from 0.232 in our controls, 0.389 in Han Chinese to 0.536 in
      Caucasians. Asthma diagnosis was associated with rs11650680 and five other SNPs
      including rs7216389 (P = 0.019-0.034), whereas atopy was associated only with
      rs11650680 (P = 0.0004). Linear regression revealed the covariates for plasma
      total IgE to be significant for rs11650680 (P = 0.008-0.0002). Haplotypic
      associations were found with atopy and increased plasma total IgE, with the
      respective odds ratios and 95% confidence intervals for TTTCCGTT haplotype to be
      0.21 and 0.09-0.52 (P = 0.0002) and 0.41 and 0.18-0.90 (P = 0.025). CONCLUSION:
      Childhood asthma and atopy are associated with chromosome 17q21 in Chinese, but
      such association may involve genes other than ORMDL3 in this region.

PMID- 19175593
TI  - Sensitization, asthma and allergic disease in young soccer players.
AB  - BACKGROUND: The aim of this study was to identify the prevalence of allergic
      disease in young soccer players compared to age-matched students and to evaluate
      if this prevalence changes as the intensity of training increases. METHODS: A
      modified ECRHS questionnaire was administered to 194 soccer players divided by
      age as Beginners (8-11 years), Juniors (12-16 years) and Under 21 (17-20 years)
      to evaluate the prevalence of allergic diseases and symptoms as well as drug
      consumption. Subjects with a positive personal history of allergic diseases
      underwent skin prick and/or patch tests. Age-matched students (n = 136) were used
      as a control group. RESULTS: The prevalence of allergic diseases was 34.5% in
      soccer players and 31.6% in control subjects (n.s.). Skin sensitization to
      inhalant allergens was detected in 14.4% of symptomatic soccer players and in
      19.2% of control students (n.s.). Patch tests were positive in 35.7% of soccer
      players and 23.0% of controls with allergic dermatitis (n.s.). The prevalence of
      allergic diseases did not significantly change in relation to the intensity of
      training. Although the relative prevalence of sensitization to perennial
      allergens and asthma was less frequent in soccer players than in controls, and
      the occurrence of exercise-induced bronchoconstriction was similar in the two
      groups, soccer players used twice as many anti-allergic and anti-asthmatic drugs
      as control students. CONCLUSIONS: An increasingly intensive training programme is
      not associated with greater risk of allergic disease in soccer players. Therapy
      regimens of allergic athletes and exercisers should be monitored more closely to
      guarantee adequate treatment yet avoid inappropriate drug use and doping
      practices.

PMID- 19175594
TI  - Comparative enzymology of native and recombinant house dust mite allergen Der p
      1.
AB  - BACKGROUND: The cysteine peptidase activity of group 1 house dust mite allergens
      is important for their allergenicity and may offer new therapeutic targets for
      allergy treatment. Hitherto, the design of specific inhibitors has been impeded
      because the availability of pure, fully active allergens has limited the
      implementation of drug screening campaigns. Similarly, investigation of the
      mechanisms by which peptidase allergens promote sensitization has also been
      restricted. Our aim was to compare the enzymology of recombinant and native forms
      of Der p 1 to establish if an easily expressed recombinant form of Der p 1 could
      be used as a drug discovery tool. METHODS: Enzymatic activity of natural and
      recombinant Der p 1 was compared fluorimetrically using a novel specific
      substrate (ADZ 50,059) and a novel specific active site titrant (ADZ 50,000). The
      effect of recombinant Der p 1 prodomain on the catalytic activity of both Der p 1
      preparations was also examined. RESULTS: Although differing substantially in
      molecular weight, the enzymological properties of recombinant and native Der p 1
      were indistinguishable. Our data show clearly by experiment that, in contrast to
      some suggestions, Der p 1 is not an enzyme of bifunctional mechanism. CONCLUSION:
      The catalytic activity of Der p 1 is tolerant of glycosylation differences that
      occur at N150 when the protein is expressed in Pichia pastoris. This suggests
      that this recombinant protein may be suitable for drug design studies and in the
      elucidation of how peptidase activity promotes sensitization to peptidase and
      nonpeptidase bystander allergens.

PMID- 19175595
TI  - A quantitative genetic analysis of intermediate asthma phenotypes.
AB  - AIM: To study the relative contribution of genetic and environmental factors to
      the correlation between exhaled nitric oxide (FeNO), airway responsiveness,
      airway obstruction, and serum total immunoglobulin E (IgE). METHODS: Within a
      sampling frame of 21,162 twin subjects, 20-49 years of age, from the Danish Twin
      Registry, a total of 575 subjects (256 intact pairs and 63 single twins) who
      either themselves and/or their co-twins reported a history of asthma at a
      nationwide questionnaire survey, were clinically examined. Traits were measured
      using standard techniques. Latent factor models were fitted to the observed data
      using maximum likelihood methods. RESULTS: Additive genetic factors explained 67%
      of the variation in FeNO, 43% in airway responsiveness, 22% in airway
      obstruction, and 81% in serum total IgE. In general, traits had genetically and
      environmentally distinct variance structures. The most substantial genetic
      similarity was observed between FeNO and serum total IgE, genetic correlation
      (rhoA) = 0.37, whereas the strongest environmental resemblance was observed
      between airway responsiveness and airway obstruction, specific environmental
      correlation (rhoE) = -0.46, and between FeNO and airway responsiveness, rhoE =
      0.34. CONCLUSIONS: Asthma is a complex disease characterized by a set of
      etiologically heterogeneous biomarkers, which likely constitute diverse targets
      of intervention.

PMID- 19175596
TI  - Norwegian adolescents with asthma are physical active and fit.
AB  - BACKGROUND: Evidence regarding habitual physical activity levels and aerobic
      fitness of asthmatic compared to nonasthmatic children and adolescents is
      contradictory, and it is unclear if low physical activity levels can contribute
      to asthma development. The present study therefore aimed to determine whether
      adolescents with asthma have reduced physical activity levels and aerobic
      fitness, or increased energy intake and body fat compared to controls. METHODS:
      From the environment and childhood asthma study in Oslo, 174 (13- to 14-year old)
      adolescents, 95 (66 boys) with and 79 (41 boys) without asthma performed maximal
      running on a treadmill with oxygen consumption measurement (aerobic fitness) and
      had the sum of four skinfolds and waist circumference recorded (body fat),
      followed by wearing an activity monitor and registering diet for four consecutive
      days. Asthma was defined by at least two of the following three criteria
      fulfilled: (1) dyspnoea, chest tightness and/or wheezing; (2) a doctor's
      diagnosis of asthma; (3) use of asthma medication. Participants with asthma used
      their regular medications. RESULTS: Neither aerobic fitness, total energy
      expenditure nor hours in moderate to very vigorous intensity physical activity
      during week and weekend differed between adolescents with and without asthma.
      Energy intake and body fat was similar in both groups. CONCLUSIONS: Total energy
      expenditure, aerobic fitness and hours in moderate to very vigorous intensity
      physical activity were not reduced and energy intake and body fat measured with
      skinfolds not increased among Norwegian adolescents with asthma.

PMID- 19175597
TI  - Impact of allergic rhinitis on asthma: effects on bronchial hyperreactivity.
AB  - BACKGROUND: Remarkable relationship exists between upper and lower airways.
      Bronchial hyperreactivity (BHR) is a paramount feature of asthma and may be
      considered a strong risk factor for the onset of asthma in patients with allergic
      rhinitis. OBJECTIVE: This study is aimed at evaluating the presence of BHR in a
      large group of patients with moderate-severe persistent allergic rhinitis alone,
      and at investigating possible risk factors related to severe BHR. METHODS: Three
      hundred and forty-two patients with moderate-severe persistent allergic rhinitis
      were prospectively and consecutively evaluated. Clinical examination, skin prick
      test, spirometry and bronchial methacholine (MCH) test were performed in all
      patients. RESULTS: Twenty-two (6.4%) patients had severe BHR, 74 (21.6%) patients
      had mild BHR and 192 (56.2%) had borderline BHR; 54 (15.8%) patients had a
      negative MCH test. The logistic regression analysis evidenced that trees and
      house dust mites sensitization (ORAdj: 8.1), rhinitis duration > 5 years (ORAdj:
      5.4) and FEV1 < or = 86% of predicted (ORAdj: 4.0) were significantly associated
      with severe BHR. The discriminative ability of this model is appreciably
      satisfactory, being the AUC = 0.90. CONCLUSION: This study highlights the close
      link between upper and lower airways and the role of some risk factors, such as
      tree and mite sensitization, > 5-year duration, and < or = 86% FEV1 values, as
      risk factors for severe BHR in patients with moderate-severe persistent allergic
      rhinitis alone. Therefore, BHR is frequently present in patients with chronic
      rhinitis and should be suspected in the presence of defined risk factors.

PMID- 19175598
TI  - Inhibition of allergic responses by CD40 gene silencing.
AB  - BACKGROUND: Gene silencing using small interfering RNA (siRNA) is a potent method
      of specifically knocking down molecular targets. Small interfering RNA is
      therapeutically promising, however, treatment of allergic diseases with siRNA has
      not been explored in vivo. The aim of this study was to evaluate therapeutic
      effects of CD40 siRNA on inhibition of allergic responses. METHODS: Mice
      sensitized with ovalbumin (OVA) and alum were treated with CD40 siRNA, scrambled
      siRNA, or phosphate buffer saline (PBS) alone, and then challenged intranasally
      with OVA. RESULTS: A significant reduction in nasal allergic symptoms was
      observed in the CD40 siRNA treated OVA-allergic mice compared to the controls of
      scrambled siRNA and PBS alone, which is correlated with the decrease of local
      eosinophil accumulation. CD40 siRNA treatment knocked down CD40 expression on
      dendritic cells (DCs) in vivo and impaired their antigen presenting function.
      Treatment with CD40 siRNA resulted in inhibition of OVA-specific T cell response
      and decrease of interleukin-4 (IL-4), IL-5, and interferon-gamma production from
      T cells stimulated with OVA. Administration of CD40 siRNA also suppressed CD40
      expression on B cells, resulting in down-regulation of OVA-specific
      immunoglobulin E (IgE), IgG1, and IgG2a levels. Additionally, increased
      regulatory T cells were observed in the CD40 siRNA treated mice. CONCLUSIONS: The
      present study demonstrates a novel therapeutic use for siRNA in allergy. CD40
      siRNA attenuated allergy through inhibition of DC and B cell functions and
      generation of regulatory T (Treg) cells.

PMID- 19175599
TI  - Respiratory virus induction of alpha-, beta- and lambda-interferons in bronchial
      epithelial cells and peripheral blood mononuclear cells.
AB  - BACKGROUND: Respiratory viruses, predominantly rhinoviruses are the major cause
      of asthma exacerbations. Impaired production of interferon-beta in rhinovirus
      infected bronchial epithelial cells (BECs) and of the newly discovered interferon
      lambdas in both BECs and bronchoalveolar lavage cells, is implicated in asthma
      exacerbation pathogenesis. Thus replacement of deficient interferon is a
      candidate new therapy for asthma exacerbations. Rhinoviruses and other
      respiratory viruses infect both BECs and macrophages, but their relative
      capacities for alpha-, beta- and lambda-interferon production are unknown.
      METHODS: To provide guidance regarding which interferon type is the best
      candidate for development for treatment/prevention of asthma exacerbations we
      investigated respiratory virus induction of alpha-, beta- and lambda-interferons
      in BECs and peripheral blood mononuclear cells (PBMCs) by reverse transferase
      polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS:
      Rhinovirus infection of BEAS-2B BECs induced interferon-alpha mRNA expression
      transiently at 8 h and interferon-beta later at 24 h while induction of
      interferon-lambda was strongly induced at both time points. At 24 h, interferon
      alpha protein was not detected, interferon-beta was weakly induced while
      interferon-lambda was strongly induced. Similar patterns of mRNA induction were
      observed in primary BECs, in response to both rhinovirus and influenza A virus
      infection, though protein levels were below assay detection limits. In PBMCs
      interferon-alpha, interferon-beta and interferon-lambda mRNAs were all strongly
      induced by rhinovirus at both 8 and 24 h and proteins were induced: interferon
      alpha>-beta>-lambda. Thus respiratory viruses induced expression of alpha-, beta-
      and lambda-interferons in BECs and PBMCs. In PBMCs interferon-alpha>-beta>-lambda
      while in BECs, interferon-lambda>-beta>-alpha. CONCLUSIONS: We conclude that
      interferon-lambdas are likely the principal interferons produced during innate
      responses to respiratory viruses in BECs and interferon-alphas in PBMCs, while
      interferon-beta is produced by both cell types.

PMID- 19175600
TI  - Hyponatremia complicating labour--rare or unrecognised? A prospective
      observational study.
AB  - OBJECTIVE: The aim of this study was to investigate the occurrence of
      hyponatraemia following delivery, with a hypothesis that hyponatraemia has a high
      prevalence in labouring women. DESIGN: Prospective observational study. SETTING:
      Consultant-led delivery suite in County Hospital, Kalmar, Sweden. SAMPLE: A total
      of 287 pregnant women at term (37 full gestational weeks). METHODS: Oral fluids
      were allowed during labour. Blood samples were collected on admission, after
      delivery, and from the umbilical artery and vein. MAIN OUTCOME MEASURE:
      Hyponatraemia defined as plasma sodium < or =130 mmol/l after delivery. RESULTS:
      Hyponatraemia was found in 16 (26%) of the 61 mothers who received more than 2500
      ml of fluid during labour. Two-thirds of fluids were orally ingested. Decrease in
      plasma sodium concentration during labour correlated with duration of labour and
      the total fluid volume administered. Analysis by multivariate logistic regression
      showed that hyponatraemia was significantly correlated with fluid volume (P <
      0.001) but not with oxytocin administration or epidural analgesia. Hyponatraemia
      correlated significantly with prolonged second stage of labour, instrumental
      delivery, and emergency caesarean section for failure to progress (P = 0.002).
      CONCLUSIONS: Hyponatraemia is not uncommon following labour. Tolerance to a water
      load is diminished during labour; therefore, even moderate fluid volumes may
      cause hyponatraemia. Women should not be encouraged to drink excessively during
      labour. Oral fluids, when permitted, should be recorded, and intravenous
      administration of hypotonic fluids should be avoided. When abundant drinking is
      unrecognised or intravenous fluid administration liberal, life-threatening
      hyponatraemia may develop. The possibility that hyponatraemia may influence
      uterine contractility merits further investigation.

PMID- 19175601
TI  - Phosphodiesterase-5 inhibitors and rosacea: report of 10 cases.

PMID- 19175602
TI  - Stem cell markers (cytokeratin 15, CD34 and nestin) in primary scarring and
      nonscarring alopecia.
AB  - BACKGROUND: Although the pathogenesis of most primary scarring alopecias is
      poorly understood, recent studies implicate the bulge region as a possible
      target. OBJECTIVES: To corroborate these results, we ascertained involvement of
      follicular bulge stem cells using a panel of antibodies that putatively targeted
      the same. METHODS: Antibodies used included anticytokeratin (CK) 15, CD34 and
      nestin on vertical and horizontal tissue sections of 50 cases of scarring and 34
      cases of nonscarring alopecia. RESULTS: Comparing expression of these markers in
      scarring vs. nonscarring alopecia, CK15 was noted in the follicular bulge region
      in 23 of 43 (53%) vs. 27 of 27 (100%) cases and in the peripheral layer of the
      outer root sheath (ORS) (upper two-thirds of the follicle) in 50 of 50 (100%) vs.
      34 of 34 (100%) cases; CD34 was noted in the peripheral layer of the ORS (below
      pilar muscle attachment) in 24 of 35 (69%) vs. 18 of 18 (100%) cases; and nestin
      was noted in the infundibular region in 18 of 46 (39%) vs. seven of 32 (22%)
      cases and in the inner aspect of the ORS (below pilar muscle attachment) in eight
      of 31 (26%) vs. 23 of 23 (100%) cases. CONCLUSIONS: Our findings of differential
      follicular localization of stem cells underscore follicular progenitor cell
      heterogeneity and suggest the target in scarring alopecia is not merely
      follicular bulge stem cells but involves stem cells in the inner and outer aspect
      of the ORS. Enhanced expression of nestin in the infundibular region in scarring
      alopecia indicates availability of an accessible, in vivo niche of potential
      utility as an autologous source of stem cells for therapeutic application.

PMID- 19175603
TI  - Induction of protoporphyrin IX by aminolaevulinic acid in actinic keratosis,
      psoriasis and normal skin: preferential porphyrin enrichment in differentiated
      cells.
AB  - BACKGROUND: In photodynamic therapy the endogenous photosensitizer protoporphyrin
      IX (PpIX) is synthesized following topical application of aminolaevulinic acid
      (ALA). However, different tissues have distinct PpIX-accumulating properties, due
      to differences in penetration of ALA through the stratum corneum and/or
      alterations in the haem cycle. Preferential PpIX accumulation has been reported
      in terminally differentiated cell cultures but ex vivo data are lacking.
      OBJECTIVES: To study the intrinsic PpIX-accumulating capabilities of skin
      explants from lesional and nonlesional skin in psoriasis and actinic keratosis,
      with normal skin serving as a control, and to study PpIX accumulation in relation
      to differentiation status in normal skin. METHODS: Skin explants from patients
      with psoriasis, actinic keratosis and normal skin were incubated with ALA and
      PpIX was measured spectrofluorometrically. PpIX was measured in basal (beta1
      integrin-positive) and suprabasal (beta1-integrin-negative) keratinocytes in
      normal skin. In addition, PpIX accumulation was studied in cell cultures at
      different levels of confluence and after induction of terminal differentiation.
      RESULTS: No significant differences in PpIX content were found between the
      different tissues. However, increased PpIX was found in beta1-integrin-negative
      compared with beta1-integrin-positive cells. In addition, in subconfluent cell
      cultures less PpIX was found compared with confluent cell cultures. Induction of
      terminal differentiation in vitro, however, resulted in less PpIX, which was
      likely to be related to cell volume. CONCLUSIONS: As no significant differences
      in PpIX synthesis could be found between the different tissue types, these data
      emphasize the importance of the penetration route of ALA through the stratum
      corneum. Preferential PpIX accumulation observed in suprabasal epidermal
      keratinocytes and confluent cell cultures points towards a terminal
      differentiation-specific effect.

PMID- 19175604
TI  - Reduction of cerebral infarct volume by apocynin requires pretreatment and is
      absent in Nox2-deficient mice.
AB  - BACKGROUND AND PURPOSE: Reactive oxygen species (ROS) derived from Nox2
      containing reduced form of nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase activity is reportedly detrimental in cerebrovascular disease. However,
      ROS generation by other Nox isoforms may have a physiological role. No Nox2
      selective inhibitors have yet been identified, and thus it is unclear whether
      isoform non-selective Nox inhibitors would necessarily improve outcome after
      stroke. We assessed the effect of apocynin on cerebrovascular ROS production and
      also on outcome following cerebral ischaemia when administered either before
      ischaemia or after cerebral reperfusion. The involvement of Nox2-containing NADPH
      oxidase in the effects of apocynin was assessed using Nox2(-/-) mice.
      EXPERIMENTAL APPROACH: Transient cerebral ischaemia was induced by 0.5 h middle
      cerebral artery occlusion followed by 23.5 h reperfusion. Mice received apocynin
      (2.5 mg.kg(-1), i.p.) either 0.5 h before ischaemia or 1 h after reperfusion. In
      situ superoxide production after cerebral ischaemia-reperfusion was measured in
      brain sections of wild-type mice at 24 h using dihydroethidium fluorescence. KEY
      RESULTS: Treatment with apocynin 0.5 h before ischaemia reduced total infarct
      volume, neurological impairment and mortality in wild-type but not Nox2(-/-)
      mice. Conversely, treatment with apocynin 1 h after initiation of reperfusion had
      no protective effect. Cerebral ischaemia and reperfusion increased superoxide
      production in the brain at 24 h, and pretreatment but not posttreatment with
      apocynin reduced superoxide levels. CONCLUSIONS AND IMPLICATIONS: Apocynin
      improves outcome following stroke when administered before ischaemia in wild-type
      but not Nox2(-/-) mice.

PMID- 19175605
TI  - Prostaglandin E(2) couples through EP(4) prostanoid receptors to induce IL-8
      production in human colonic epithelial cell lines.
AB  - BACKGROUND AND PURPOSE: Prostaglandin (PG) E(2) and interleukin (IL)-8 are
      simultaneously increased during the inflammation that characterizes numerous
      pathologies such as inflammatory bowel disease. IL-8 is a potent neutrophil chemo
      attractant and activator, and can initiate and/or exacerbate tissue injury.
      PGE(2) signals principally through prostanoid receptors of the EP(2) and/or EP(4)
      subtypes to promote cAMP-dependent cellular functions. The aim of this study was
      to identify the role of the EP(2) and EP(4) receptor subtype(s) on two human
      colonic epithelial cell lines (Caco-2 and T84), in regulating PGE(2)-induced IL-8
      production. EXPERIMENTAL APPROACH: To identify the causative receptor, we knocked
      down and over-expressed EP(2) and EP(4) receptor subtypes in colonic epithelial
      cells and studied the effect of several selective EP(2)/EP(4) receptor agonists
      and antagonists. The inductions of IL-8 and EP receptor mRNA and protein
      expression were determined by real-time PCR and western blot analysis. The
      affinity of PGE(2) and Bmax values for the EP(2) and EP(4) receptor on colonic
      epithelial cells were determined by radioligand-binding assays with [(3)H]PGE(2).
      KEY RESULTS: PGE(2) had the highest affinity for the EP(4) receptor subtype and
      promoted a robust stimulation of cAMP-dependent IL-8 synthesis. This effect was
      mimicked by a selective EP(4) receptor agonist, ONO-AE1-329, and abolished by
      silencing the EP(4) receptor gene by using siRNA techniques, a selective EP(4)
      receptor antagonist (ONO-AE3-208) and a selective inhibitor (Rp-cAMP) of cAMP
      dependent protein kinase. CONCLUSIONS AND IMPLICATIONS: These findings suggest
      that initiation and progression of colonic inflammation induced by IL-8 could be
      mediated, at least in part, by PGE(2) acting via the EP(4) receptor subtype.

PMID- 19175606
TI  - Activated hepatic stellate cells promote tumorigenicity of hepatocellular
      carcinoma.
AB  - Liver cirrhosis is the main risk factor for the development of hepatocellular
      carcinoma (HCC). Activated hepatic stellate cells (HSC) are the effector cells of
      hepatic fibrosis and also infiltrate the HCC stroma where they might play a
      critical role in HCC progression. Here we aimed to analyze the effects of
      activated HSC on the proliferation and growth of HCC cell lines in vitro and in
      vivo. Conditioned media (CM) collected from HSC significantly induced
      proliferation and migration of HCC cells cultured in monolayers. In a 3
      dimensional spheroid coculture system, HSC promoted HCC growth and diminished the
      extent of central necrosis. In accordance, in vivo simultaneous implantation of
      HSC and HCC cells into nude mice promoted tumor growth and invasiveness, and
      inhibited necrosis formation. As potential mechanism of the tumorigenic effects
      of HSC we identified activation of NFkappaB and extracellular-regulated kinase
      (ERK) in HCC cells, two signaling cascades that play a crucial role in HCC
      progression. In summary, our data indicate that stromal HSC promotes HCC
      progression and suggest the HSC-HCC interaction as an interesting tumor
      differentiation-independent target for therapy of this highly aggressive cancer.

PMID- 19175607
TI  - Deletion of the ectodomain unleashes the transforming, invasive, and tumorigenic
      potential of the MET oncogene.
AB  - The c-MET proto-oncogene, encoding the p190 hepatocyte growth factor tyrosine
      kinase receptor, can acquire oncogenic potential by multiple mechanisms, such as
      gene rearrangement, amplification and overexpression, point mutation, and ectopic
      expression, all resulting in its constitutive activation. Hepatocyte growth
      factor receptor truncated forms are generated by post-translational cleavage:
      p140 and p130 lack the kinase domain and are inactive. Their C-terminal remnant
      fragments are generally undetectable in normal cells, but a membrane-associated
      truncated form is recognized by anti-C-terminus antibodies in some human tumors,
      suggesting that a hepatocyte growth factor receptor lacking the ectodomain, but
      retaining the transmembrane and intracellular domains (Met-EC-), could acquire
      oncogenic properties. Herein we show that NIH-3T3 cells transduced with MET-EC-
      expressed a membrane-associated constitutively tyrosine-phosphorylated 60-kDa
      protein and, similarly to NIH-3T3 cells expressing the cytosolic oncoprotein Tpr
      Met, showed activated extracellular regulated kinase 1/2 mitogen-activated
      protein kinase and Akt downstream transducers. Compared to control NIH-3T3 cells,
      NIH-3T3-Met-EC- cells grew faster and showed anchorage-independent growth and
      invasive properties in all aspects similar to cells expressing the transforming
      TPR-MET. Nude female mice injected subcutaneously with NIH-3T3-Met-EC- cells
      developed visible tumors, displaying the typical morphology of carcinomas with
      polygonal cells, in contrast to sarcomas with spindle-shaped cells induced by the
      injection of NIH-3T3-Tpr-Met cells. It is suggested that the different
      subcellular localization of the oncoproteins, more than differences in signal
      transduction, could be responsible for the tumor phenotype. All together, these
      data show that deletion of the ectodomain activates the hepatocyte growth factor
      receptor and its downstream signaling pathways, unleashing its transforming,
      invasive, and tumorigenic potential.

PMID- 19175609
TI  - Cerebral venous thrombosis after epidural blood patch: casual or causal
      association?

PMID- 19175610
TI  - Space headache: a new secondary headache.
AB  - Headache is a common, but rarely voiced, complaint during space flights, usually
      attributed to space motion sickness (SMS). We used a specifically designed
      questionnaire based on the criteria of the International Classification of
      Headache Disorders, 2nd edn (ICHD-II). Of the 16 male and one female astronauts
      who participated in the survey, 12 (71%) reported having experienced at least one
      headache episode while in space, whereas they had not suffered from headache when
      on earth. There were in total 21 space headache episodes, of moderate to severe
      intensity in 71%. In two astronauts (12%) the headache and associated symptoms
      would match the ICHD-II criteria for migraine and in three (18%) astronauts for
      tension-type headache; in 12 (70%) astronauts the headache was non-specific. The
      vast majority of headache episodes (76%) were not associated with symptoms of
      SMS. We conclude that space flights may trigger headaches without other SMS
      symptoms in otherwise 'super-healthy' male subjects. We propose to classify space
      headache as a separate entity among the secondary headaches attributed to
      disorders of homeostasis.

PMID- 19175611
TI  - Quality of life in children with primary headache in a general hospital.
AB  - Knowledge on the quality of life of children with headache is lacking. Until now
      only a few studies in this field have provided information on a limited number of
      life domains. The aim of this study was to assess the quality of life in a
      comprehensive number of life domains in children with primary headache presenting
      at an out-patient paediatric department in a general hospital. From October 2003
      to October 2005 all children referred to the out-patient paediatric department of
      the Vlietland Hospital because of primary headache were investigated by protocol.
      A thorough history was taken and a general physical and neurological examination
      was performed. The International Headache Society criteria were used for
      classification. Quality of life (QoL) was measured using the Dutch version of the
      Child Health Questionnaire (CHQ-PF50 Dutch edition) and compared with data from a
      previously investigated cohort of healthy children from the same region, and with
      data from a cohort of children from the USA with asthma or with attention deficit
      hyperactivity disorder (ADHD), investigated with the CHQ-PF50. A total of 70
      primary headache patients were included in the study (25 with tension-type
      headache, 36 with migraine, seven with chronic tension-type headache, two with
      both tension-type headache and migraine). Their mean age was 10.6 years (range 4
      17 years); 37 children were male. On all but one subscale (self-esteem) the QoL
      of the children with primary headache was decreased compared with the cohort of
      healthy children, especially on the domains of mental health, parental impact
      time and family cohesion. Compared with the cohort of children with asthma the
      QoL was significantly worse for our headache group on seven subscales and
      significantly better on one subscale (general health perception). Compared with
      the cohort of children with ADHD, the QoL was significantly worse on six
      subscales but significantly better on three subscales. There were no significant
      differences on any QoL subscale between children with tension-type headache and
      children with migraine. We conclude that the QoL in children with primary
      headache presenting at the out-patient paediatric department of a general
      hospital seems to be considerably diminished. Furthermore, we conclude that, in
      this population there is no difference in QoL between children with tension-type
      headache and those with migraine.

PMID- 19175612
TI  - Mammography-related breast pain is associated with migraine.
AB  - There is little information about the perception of experimentally induced
      extracephalic pain in migraine. This study investigates the associations between
      mammography-related pain and migraine. A neurologist clinically assessed 630
      women aged 40-74 years attending a population-based breast cancer screening
      programme. Headache criteria proposed by the International Headache Society were
      used. Mammography-related pain was measured on a 100-mm visual analogue scale.
      High levels of mammography-related pain were associated with migraine. This
      association was related to mammographic examination during the early follicular
      phase and menopausal status, but unrelated to differences in age, compression
      pressure, education, current use of hormonal replacement therapy, anxiety, and
      recent use of analgesics and antimigraine medication. The results of the present
      study indicate that migraine and compression-induced breast pain are related.

PMID- 19175613
TI  - Large-scale screening and subsequent effects of migraine treatment on the work
      floor in the Netherlands.
AB  - In a large retail business group the ID Migraine Screening Test was sent to
      employees with three or more absences from work in the past year (n = 2893).
      Employees with positive results were invited for a neurological consultation and
      migraine patients were randomly assigned to: first attack 'treated as usual' and
      the second attack treated with 40 mg eletriptan, or reversed order. Of the 2893
      employees, 799 responded (28%), 260 were positively screened for migraine (33%),
      84 patients were diagnosed by a neurologist and 41 of the 75 included patients
      completed the protocol. Eletriptan induced pain-free response in 33.3% of the
      patients at 4 h compared with 0% after 'non-specific' treatment (P = 0.03).
      Eletriptan also significantly improved quality of life, but differences in
      absence from work and productivity loss could not be detected. In conclusion, in
      company screening can be beneficial for undertreated employees, but
      implementation obstacles can reduce the effectiveness of screening.

PMID- 19175614
TI  - The effect of transcutaneous electrical nerve stimulation in the treatment of
      lichen simplex: a prospective study.
AB  - BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) has recently
      emerged as a possible effective treatment for pruritic dermatoses. Lichen simplex
      (LS) is one such condition, which may persist despite intensive topical
      treatments. AIM: To investigate the efficacy of TENS treatment in relieving
      pruritus in lichen simplex. METHODS: In total, 22 patients with LS unresponsive
      to topical corticosteroids underwent TENS treatment. The patients rated the
      pruritus intensity on a visual analogue scale (VAS). RESULTS: The mean reduction
      in VAS score from baseline to the end of 4 weeks treatment was 4.50 (95% CI 3.65
      5.34) for all patients. The difference between the baseline and at the end of the
      study was significant (P < 0.01). By the end of the study, 18 (80%) of the
      subjects experienced a reduction in pruritus intensity of > 50%. CONCLUSION: From
      our clinical observation, we suggest that TENS may prove to be a useful and well
      tolerated treatment modality for the treatment of pruritus in patients with LS.

PMID- 19175615
TI  - Two cases of dyshidrosiform pemphigoid with different presentations.
AB  - We report two cases of dyshidrosiform pemphigoid (DP) with different
      presentations. One patient was a 65-year-old Japanese man, who had been diagnosed
      with dyshidrosis and had been treated before visiting our hospital. When we
      stopped all treatments, the vesicles increased and spread to the trunk and limbs.
      We made a diagnosis of vesicular pemphigoid (VP) that was concomitant with or
      transformed from DP. Using Western blotting, the sera reacted with antigens with
      molecular weights of 60 and 180 kDa. The 60-kDa antigen has not been found
      previously in the sera of patients with VP. The other patient was a 94-year-old
      Japanese woman, who presented with redness and swelling with bullae on the
      palmoplantar areas. Five days later, areas of oedematous erythema, as seen in
      prototypical bullous pemphigoid (BP), developed on the limbs. Study of the
      distribution of the BP antigen may elucidate the mechanisms involved in localized
      forms of BP such as DP.

PMID- 19175616
TI  - Hair removal with the long-pulse alexandrite and long-pulse Nd:YAG lasers is safe
      and well tolerated in children.
AB  - BACKGROUND: Children with excessive hair may have severe psychological
      consequences. Laser hair removal in adults is known to be safe and well
      tolerated, but this is less well established in children. OBJECTIVE: To describe
      our experience with laser hair removal in children, and to investigate the safety
      and tolerability of this procedure in children. METHODS: The case records of 24
      children aged < 16 years, who had received a minimum of three treatments for hair
      removal were analysed retrospectively. For patients with Fitzpatrick skin
      phototype II-IV, the lasers used were a long-pulse alexandrite (755 nm) with
      either continuous chilled-air cooling at fluences of 16-27 J/cm(2) or a long
      pulse alexandrite with cryogen cooling at fluences of 16-32 J/cm(2). For patients
      with Fitzpatrick skin phototype IV-VI, lasers used were a long-pulse Nd:YAG (1064
      nm) with a chilled contact sapphire tip at fluences of 20-35 J/cm(2) or a long
      pulse Nd:YAG with cryogen cooling at fluences of 16-26 J/cm(2). RESULTS: Mean age
      at first treatment was 12.3 years. Diagnoses were constitutional hirsutism (14
      patients), polycystic ovarian syndrome (five), congenital melanocytic naevus
      (two), generalized hypertrichosis (two) and naevoid hypertrichosis (one). One
      patient required a general anaesthetic, eight required topical anaesthetic cream,
      and 15 did not require any form of anaesthesia. Intolerable discomfort requiring
      adjustment in fluence was the only recorded side-effect, affecting two cases.
      There were no incidences of blistering, infection, dyspigmentation or scarring.
      CONCLUSION: When administered appropriately, laser hair removal is safe and well
      tolerated in children aged < 16 years.

PMID- 19175617
TI  - A randomized controlled trial of high-permeability haemodialysis against
      conventional haemodialysis in the treatment of uraemic pruritus.
AB  - BACKGROUND: Uraemic pruritus (UP) is one of the most common problems in patients
      with chronic renal failure. Owing to the complexity of UP, no specific treatment
      is currently available. Recently, the accumulated toxins of mid and macro
      molecules in advanced renal failure have been proposed to play an important role
      in the mediation of pruritus. AIM: To evaluate the effect of high permeability
      haemodialysis (HPHD) against conventional haemodialysis (CHD) on UP. METHODS: A
      randomized, prospective, double-blind study was performed to compare the efficacy
      of HPHD against CHD in the treatment of UP. In total, 116 patients with chronic
      renal failure and UP were enrolled in the trial. A visual analogue scale (VAS)
      was used to assess the severity of itch. The toxins of mid and macro molecules
      [beta2-microglobulin (beta2-MG), parathyroid hormone (PTH), respectively] were
      measured, and the solute clearance rate (SCR) and urea clearance index (Kt/V)
      were also determined. RESULTS: The pruritus scores in the HPHD group were
      significantly lower (2.23 +/- 1.05) than those in the CHD group (5.45 +/- 1.91, P
      = 0.012), although the SCR and Kt/V showed no significance between the two groups
      (SCR P = 0.075; Kt/V P = 0.082). It was found that HPHD and CHD achieved a
      reasonable clearance rate of blood urea nitrogen and creatinine. However, the
      toxins of mid and macro molecules were markedly reduced in the blood of patients
      treated with HPHD, compared with those treated with CHD. The concentrations of
      PTH and beta2-MG were significantly reduced by HPHD in comparison with CHD (PTH
      119.27 +/- 8.41 vs. 165.18 +/- 9.37 pmol/L, P = 0.01; beta2-MG 3.39 +/- 0.76 vs.
      5.92+/- 1.58 g/mL, P = 0.012). CONCLUSIONS: These data indicate that HPHD can
      efficiently relieve UP through clearance of accumulated mid and macro molecules
      in vivo. This further supports the hypothesis that these molecules are involved
      in UP.

PMID- 19175618
TI  - An online survey of the use of digital cameras by members of the British
      Association of Dermatologists.
AB  - The use of digital cameras by clinicians is increasing, and raises issues
      concerning patient consent and confidentiality. An online survey of members of
      the British Association of Dermatologists was conducted using an anonymous
      questionnaire. In total, 339 individuals completed the survey, a response rate of
      37.6%. The survey shows that there are variations in the type of consent obtained
      by clinicians taking digital images of patients, and the methods used to store
      images are not always compliant with current UK legislation. Guidelines would
      help to improve and standardize the practice of clinicians who take digital
      images of patients.

PMID- 19175619
TI  - Enhanced expression of interferon-inducible protein-10 correlates with disease
      activity and clinical manifestations in systemic lupus erythematosus.
AB  - Our objective was to investigate the serum levels of interferon-inducible protein
      10 (IP-10) in systemic lupus erythematosus (SLE) and their correlation with
      disease activity and organ manifestations. Serum IP-10 levels were assessed in
      464 SLE patients and 50 healthy donors. Disease activity was assessed by the
      revised SLE Activity Measure, and the concomitant active organ manifestations,
      anti-ds DNA antibody titres, complement levels and erythrocyte sedimentation
      rates recorded. Peripheral blood mononuclear cell (PBMC) synthesis of IP-10 in
      SLE patients and controls was determined by in vitro cultures stimulated with
      mitogen or lipopolysaccharide. Elevated serum IP-10 levels were observed in SLE
      patients, which were significantly higher in the presence of active
      haematological and mucocutaneous manifestations. SLE PBMCs exhibited enhanced
      spontaneous IP-10 production in vitro. Serial IP-10 levels correlated with
      longitudinal change in SLE activity, even at low levels where anti-dsDNA antibody
      and complement levels remain unchanged. These data demonstrate that IP-10 levels
      are increased in SLE and serum IP-10 may represent a more sensitive marker for
      monitoring disease activity than standard serological tests.

PMID- 19175621
TI  - Occurrence of extended-spectrum beta-lactamase-producing Salmonella enterica in
      northern Spain with evidence of CTX-M-9 clonal spread among animals and humans.
AB  - Among the 1233 Salmonella enterica isolates obtained in two Spanish hospitals,
      five isolates (0.4%) (serovars: Virchow, four; Livingstone, one) had the
      phenotype of an extended-spectrum beta-lactamase (ESBL) producer. The genetic
      characterization of the ESBL of S. enterica Livingstone revealed a bla(SHV-2)
      gene. The bla(CTX-M-10) gene in a phage-related genetic environment was found in
      one S. enterica Virchow isolate, and the bla(CTX-M-9) gene within the In60
      integron was found in the three remaining Virchow isolates. These three isolates
      presented indistinguishable or closely related pulsed-field gel electrophoresis
      patterns among themselves and also as compared with the two other bla(CTX-M-9)
      containing isolates previously obtained from animals. ESBL production is an
      emerging mechanism of resistance in S. enterica in the two studied hospitals.

PMID- 19175620
TI  - L-carnitine, a diet component and organic cation transporter OCTN ligand,
      displays immunosuppressive properties and abrogates intestinal inflammation.
AB  - Allele variants in the L-carnitine (LCAR) transporters OCTN1 (SLC22A4, 1672 C -->
      T) and OCTN2 (SLC22A5, -207 G --> C) have been implicated in susceptibility to
      Crohn's disease (CD). LCAR is consumed in the diet and transported actively from
      the intestinal lumen via the organic cation transporter OCTN2. While recognized
      mainly for its role in fatty acid metabolism, several lines of evidence suggest
      that LCAR may also display immunosuppressive properties. This study sought to
      investigate the immunomodulatory capacity of LCAR on antigen-presenting cell
      (APC) and CD4+ T cell function by examining cytokine production and the
      expression of activation markers in LCAR-supplemented and deficient cell culture
      systems. The therapeutic efficacy of its systemic administration was then
      evaluated during the establishment of colonic inflammation in vivo. LCAR
      treatment significantly inhibited both APC and CD4+ T cell function, as assessed
      by the expression of classical activation markers, proliferation and cytokine
      production. Carnitine deficiency resulted in the hyperactivation of CD4+ T cells
      and enhanced cytokine production. In vivo, protection from trinitrobenzene
      sulphonic acid colitis was observed in LCAR-treated mice and was attributed to
      the abrogation of both innate [interleukin (IL)-1beta and IL-6 production] and
      adaptive (T cell proliferation in draining lymph nodes) immune responses. LCAR
      therapy may therefore represent a novel alternative therapeutic strategy and
      highlights the role of diet in CD.

PMID- 19175622
TI  - Clinical presentations and epidemiology of beta-haemolytic streptococcal
      bacteraemia: a population-based study.
AB  - In this population-based study, all 314 episodes of beta-haemolytic streptococcal
      bacteraemia in adult patients in the Pirkanmaa area, Finland, during the 10-year
      period 1995-2004 were retrospectively reviewed. Altogether, 92 cases of
      bacteraemia caused by Lancefield group A beta-haemolytic streptococci (GAS), 76
      caused by group B beta-haemolytic streptococci (GBS), 18 caused by group C beta
      haemolytic streptococci (GCS) and 128 caused by group G beta-haemolytic
      streptococci (GGS) were identified. The most important finding was that the
      incidence of GGS increased during the study period. Disruption of the cutaneous
      barrier was a very common predisposing factor in GAS and GGS bacteraemias. Skin
      infections were the presenting clinical manifestations in two-thirds of GAS and
      GGS bacteraemias.

PMID- 19175623
TI  - Incontinence rates after cutting seton treatment for anal fistula.
AB  - OBJECTIVE: To determine the incidence of anal incontinence after the use of
      cutting seton treatment for anal fistula. METHOD: Literature searches were
      performed on PubMed, MEDLINE and Google Scholar using the words 'cutting
      seton(s)', 'seton(s)' and 'anal fistula'. An analysis of the data in the
      collected references was performed. RESULTS: The average rate of incontinence
      following cutting seton use was 12%. The rate of incontinence increased as the
      location of the internal opening of the fistula moved more proximally. In the
      studies that described the types of incontinence, liquid stool was the most
      common followed closely by flatus incontinence. Incontinence associated with the
      treatment of fistulas defined as nonspecific cryptoglandular in nature was 18%.
      CONCLUSION: The high incontinence rates that result from the use of cutting
      setons suggest that this commonly used therapy can damage the continence
      musculature. Other techniques that do not involve cutting the sphincter, when
      available, should be preferred, especially for higher fistulas.

PMID- 19175624
TI  - Anastomotic leakage after anterior resection for rectal cancer: risk factors.
AB  - OBJECTIVE: The study aimed to identify risk factors for clinical anastomotic
      leakage (AL) after anterior resection for rectal cancer in a consecutive national
      cohort. METHOD: All patients with an initial first diagnosis of colorectal
      adenocarcinoma were prospectively registered in a national database. The register
      included 1495 patients who had had a curative anterior resection between May 2001
      and December 2004. The association of a number of patient- and procedure-related
      factors with clinical AL after anterior resection was analysed in a cohort
      design. RESULTS: Anastomotic leakages occurred in 163 (11%) patients. In a
      multivariate analysis, the risk of AL was significantly increased in patients
      with tumours located below 10 cm from the anal verge if no faecal diversion was
      undertaken (OR 5.37 5 cm (tumour level from anal verge), 95% CI 2.10-13.7, OR
      3.57 7 cm, CI 1.81-7.07 and OR 1.96 10 cm, CI 1.22-3.10), in male patients (OR
      2.36, CI 1.18-4.71), in smokers (OR 1.88, CI 1.02-3.46), and perioperative
      bleeding (OR 1.05 for intervals of 100 ml blood loss, CI 1.02-1.07). CONCLUSION:
      Anastomotic leakage after anterior resection for low rectal tumours is related to
      the level, male gender, smoking and perioperative bleeding. Faecal diversion is
      advisable after total mesorectal excision of low rectal tumours in order to
      prevent AL.

PMID- 19175627
TI  - Morbidity and mortality after closure of loop ileostomy.
AB  - BACKGROUND: A temporary loop ileostomy is commonly used to protect low pelvic
      anastomoses. Closure is associated with morbidity and mortality. This study
      investigated patterns of complications after loop ileostomy closure and factors
      associated with morbidity and mortality. METHOD: A review was performed of
      patients who underwent loop ileostomy closure between 1999 and 2005. RESULTS:
      Three hundred and twenty-five patients underwent closure of loop ileostomy.
      Reasons for primary surgery were: anterior resection for cancer (n = 160, 49%),
      ileal pouch-anal anastomosis (n = 114, 35%), diverticular disease (n = 25, 8%),
      Crohn's colitis (n = 4, 1%) and other conditions (n = 22, 7%). Overall mortality
      was 2.5% (n = 8) and morbidity was 22.8% (n = 74). Thirty-two patients (10%)
      developed small bowel obstruction, of whom seven required operative intervention.
      Overall, the re-operation rate in this series was 28 patients (8.6%). Thirteen
      (4%) patients had an anastomotic leak of whom 12 patients had re-operation.
      Preoperative anaemia was significantly associated with leakage (Hb < 11 g/dl; n =
      65, P = 0.033). The leakage rate was lower after a stapled anastomosis than a
      hand-sutured anastomosis (4/203 vs 9/122; P = 0.039). Hypo-albuminaemia (albumin
      < 34 g/l) was significantly associated with mortality (n = 46, P < 0.001).
      CONCLUSIONS: Loop ileostomy closure is associated with morbidity and mortality.
      Anaemia and hypo-albuminaemia may be associated with poor outcome.

PMID- 19175625
TI  - STARR with Contour Transtar: prospective multicentre European study.
AB  - OBJECTIVE: The stapled transanal rectal resection (STARR) in patients with
      defecation disorders is limited by the shape and capacity of the circular
      stapler. A new device has been recently developed, the Contour Transtar stapler,
      in order to improve the safety and effectiveness of the STARR technique. The
      study has been designed to confirm this declaration. METHOD: From January to June
      2007 a prospective European multicentre study of consecutive patients with
      defecation disorder caused by internal rectal prolapse underwent the new STARR
      technique. The assessment of perioperative morbidity and functional outcome after
      6 weeks, 3 and 12 months was documented by different scores. RESULTS: In all 75
      patients, median age 64, the Transtar procedure was performed with 9%
      intraoperative difficulties, 7% postoperative complications and no mortality. The
      mean reduction of the ODS score was -15.6 (95%-CI: -17.3 to -13.8, P < 0.0001),
      mean reduction of SSS was -12.6 (95%-CI: -14.2 to -11.2; P < 0.0001). 41% stated
      improvement of their continence status by CCF score, only 4 patients (5%) had
      deterioration. CONCLUSION: The Transtar procedure is technically demanding, with
      good functional results similar to the conventional STARR.

PMID- 19175628
TI  - Three-dimensional magnetic image guided percutaneous endoscopic sigmoidopexy for
      the treatment of recurrent sigmoid volvulus.

PMID- 19175629
TI  - Colonic tattooing in laparoscopic surgery - making the mark?
AB  - OBJECTIVE: Laparoscopic surgery for colorectal cancer is now widespread. Small
      lesions in the colon can be difficult to palpate and with lack of tactile
      sensation, it is essential to accurately localize them preoperatively. This is a
      review article on current methods of tattooing including the use of different
      agents and associated complications. Aim To review current techniques in
      preoperative tumour localization and methods used for colonic tattooing including
      agents used, dosage and potential complications. METHOD: A literature search
      (Medline and Pubmed) was performed with manual cross referencing of all articles
      related to colonic tattooing. RESULTS: Methods for localizing colonic tumours for
      laparoscopic resection include preoperative barium enema examination, CT
      colonography and intraoperative colonoscopy. The most effective method is,
      however, by tattooing with India ink performed endoscopically before surgery.
      CONCLUSION: India ink is a reliable method of marking tumour location within the
      colon as prelude to laparoscopic resection. Surgeons must, however, be aware of
      potential complications associated with this technique.

PMID- 19175630
TI  - Haematoma of the sigmoid colon secondary to Ehlers Danlos Syndrome presenting as
      a colonic tumour.
AB  - Ehlers Danlos Syndrome (EDS) is a collective term for a number of connective
      tissue disorders. Vascular rupture and dissection are well-documented sequelae as
      is gastrointestinal perforation. We present a rare presentation where dissection
      of the bowel wall presented as a suspected sigmoid colon tumour.

PMID- 19175631
TI  - Successful treatment of extensive splanchnic arterial and portal vein thrombosis
      associated with ulcerative colitis.
AB  - Venous and arterial thromboembolism is a significant cause of morbidity and
      mortality in patients with ulcerative colitis (UC). Arterial thrombosis of the
      splanchnic region is a rare event with a very high mortality rate. Furthermore,
      it represents a challenging complication since it tends to be overlooked and
      misinterpreted as a clinical exacerbation of UC. We present the case of a 62-year
      old female with pancolonic UC complicated by an extensive arterial thrombosis
      involving the aorta, the celiac trunk, the hepatic, gastric and splenic arteries
      and the superior mesenteric artery. A thrombosis of the splenic vein extending
      into the proximal portal vein was also present. The patient was successfully
      treated by a combined interventional-radiological and surgical treatment. We
      discuss the rationale behind our management of this case and review the
      literature on splanchnic arterial thrombosis associated with UC.

PMID- 19175632
TI  - Rectal cancer with macroscopic peritoneal involvement--clinical challenges and
      consequences.
AB  - OBJECTIVE: In gastrointestinal cancer, serosal involvement indicates advanced
      disease. We looked at the possible role of clinical peritoneal involvement (CPI)
      in local recurrences (LRs) and the overall survival of patients with rectal
      cancer (RC). METHOD: Between 1993 and 2002, 6404 patients were diagnosed with RC.
      Based on macroscopic findings at surgery and corresponding histological findings,
      166 patients (3%) had CPI. Surgery was stratified according to type and extent of
      operation: as resective or nonresective surgery and as curative (R0) or
      noncurative (R1 or R2) resection. RESULTS: The presence of CPI was a negative
      factor for survival with a median of 15 months (95% CI, 12-19) in the presence of
      CPI compared with 65 months (95% CI, 61-70) without it (P < 0.001). In R0
      resections, the median survival was 97 months (95% CI, 90-102) in patients
      without CPI compared with 48 months (95% CI, 22-74) in patients with CPI (P <
      0.001). In R1 or R2 resections, the median survival was 16 months (95% CI, 15-17)
      in the absence of CPI and 9 months (95% CI, 8-10) in the presence of CPI. The LR
      rate in patients without CPI was 10.2% compared with 15.7% in patients with CPI
      (P = 0.022). CONCLUSIONS: Clinical peritoneal involvement is a significant
      detrimental prognostic factor for the LR of RC and survival in the absence of
      metastases. Observations from this large national cohort add to what is known
      about peritoneal involvement. Diagnosed CPI should be taken into consideration
      when adjuvant treatment strategies are addressed.

PMID- 19175633
TI  - Perioperative care in colorectal surgery: current practice patterns and opinions.
AB  - Objective Evidence regarding perioperative care in colorectal surgery has
      recently increased, leading to changes in classical clinical procedures that make
      the perioperative period safer and shorter. This survey aimed to evaluate the
      opinions of Spanish colorectal surgeons on the perioperative management of their
      patients. Method Emailed surveys submitted to the members of Spanish
      Coloproctological Associations. Results One hundred and thirty-one (31.7%) of the
      413 members participated in the study and responded thus: 21% use clinical
      pathways and 8% use fast track (FT); 36% use epidural analgesia in colonic
      surgery and 57% in rectal; 40% use warm air and 23% warm fluids to maintain
      intraoperative normothermia; 53% prescribe >/= 3000 ml. of iv fluids on the first
      postoperative day and 6.2%</= 2000 ml; 43% never use nasogastric tubes. Oral
      intake was initiated by 23.5% on the first day, and by 50% when peristalsis
      began, with an earlier tendency in laparoscopic surgery; 43% believed oral intake
      reduces ileus, but 12% considered it dangerous. Board accreditation and
      experience in Coloproctology were significantly associated with a lesser use of
      nasogastric tubes and earlier feeding. Sixty-nine per cent considered FT reduces
      postoperative stay and 44% thought that it minimizes complications. Conclusion
      Spanish surgeons maintain a classical procedural policy, but show tendencies
      towards optimizing patients' care.

PMID- 19175634
TI  - The value of routine histopathological analysis in patients with fistula in-ano.
AB  - OBJECTIVE: To determine the positive yield of routine histopathology in patients
      undergoing surgery for fistula in-ano. METHOD: Histopathology reports of all the
      patients who underwent surgery for fistulae-in-ano over a period of 36 months
      were reviewed. RESULTS: Analysis included 84 patients of which 73 (87%) were male
      subjects. The mean age was 39.4 years (range 11-68). Forty-one (49%) had
      recurrent fistulae. Granulomatous diseases such as Crohn's disease and
      tuberculosis (TB) were suspected in six patients. However, of the six patients,
      confirmation of the disease status was obtained only in three patients: stains
      for acid-fast bacilli confirmed TB in two (2.4%) patients and colonoscopy and
      biopsy confirmed Crohn's disease in one (1.2%) patient. All three patients had
      recurrent fistulae. CONCLUSION: As the positive yield of routine histopathology
      is minimal, we do not recommend routine histopathology for fistula in-ano, except
      for those presenting with recurrent fistulae and those with clinical suspicion of
      an underlying disease such as TB, HIV or Crohn's disease.

PMID- 19175635
TI  - Hodgkin's disease of appendix: report of a case.
AB  - BACKGROUND: A number of cases of non Hodgkin's lymphoma of the appendix have been
      described, but Hodgkin's lymphoma is extremely rare. To our knowledge there are
      only two reports up to 1966 and none since then. METHOD: We report a case of a 65
      year-old gentleman who was treated for suspected Crohn's disease. He failed to
      respond to medical treatment and underwent right haemicolectomy. The resected
      segment of bowel demonstrated classical Hodgkin's disease originating in the
      appendix. He recovered well from the operation and responded well to
      postoperative chemotherapy. CONCLUSION: Hodgkin's lymphoma of appendix is
      extremely rare. This case demonstrates the significance of repeated clinical
      evaluation of patients particularly in the absence of expected response to
      therapy.

PMID- 19175636
TI  - Recurrent lower gastrointestinal bleeding secondary to cytomegalovirus-associated
      colonic ulcer in a non human immunodeficiency virus infected patient: timely
      diagnosis and treatment averted surgery.
AB  - Mr C, a 68-year-old Chinese male with diabetes mellitus, previous stroke and
      ischaemic cardiomyopathy on clopidogrel, presented with haematochezia.
      Colonoscopy showed a sigmoid ulcer, which was treated endoscopically. Histology
      of the biopsy from the ulcer revealed non-specific changes. However, he presented
      with recurrent bleeding from this non-healing sigmoid ulcer. A review of the
      histologic specimen revealed CMV intranuclear inclusion bodies. He was treated
      with intravenous ganciclovir, with no further hematochezia.

PMID- 19175637
TI  - Management of the asymptomatic primary in the palliative treatment of metastatic
      colorectal cancer.
AB  - OBJECTIVE: The management of the asymptomatic primary in stage IV colorectal
      cancer presents a dilemma. There is an increased morbidity and mortality from
      surgical resection. Nonresectional management of the primary is associated with
      the risks of obstruction, perforation or haemorrhage. Our practice in patients
      with stage IV disease is palliative chemotherapy and symptom control. We reviewed
      our nonoperatively managed patients with colorectal liver metastases in order to
      identify the percentage of patients requiring urgent operative interventions for
      symptoms related to the primary. SUBJECTS/PATIENTS AND METHOD: A retrospective
      review of all patients treated for stage IV disease at our institution from 2003
      2006 was undertaken. Patients were identified from multidisciplinary team (MDT)
      records. Demographic detail, treatment, and follow-up data were extracted from
      hospital records. These were analysed with Microsoft Excel. RESULTS: Thirty-seven
      patients were identified. 26 Male:11 Female. Median age 63 years (range 38-78).
      The median survival from diagnosis was 14 months. Three (8%) patients developed
      obstruction whilst having palliative chemotherapy. Two required a defunctioning
      stoma, and one was treated by means of a stent. There were no similarities
      between these three patients in terms of age, sex, site or stage of primary,
      volume of liver metastases, and alkaline phosphatase (ALP) or carcinoembryonic
      antigen (CEA) levels. CONCLUSION: Of 37 patients initially treated palliatively
      for stage IV colorectal cancer, 92% required no surgical treatment of their
      primary. Therefore it is the experience of this MDT that it is acceptable to
      treat such patients in an expectant manner. It is not possible to predict those
      patients, likely to require surgical intervention.

PMID- 19175638
TI  - Primary anastomosis vs Hartmann's procedure in patients undergoing emergency left
      colectomy for perforated diverticulitis.
AB  - OBJECTIVE: Comparison of primary anastomosis (PA) and Hartmann's procedure (HP)
      in perforated diverticulitis is biased as the patient groups are different in
      age, comorbidity and severity of disease. Still, PA has been advocated as the
      procedure of choice. The aim of this study was to compare the two surgical
      procedures after eliminating this selection bias using a propensity score model.
      METHOD: Sixty-five HP and 46 PA patients who underwent emergency laparotomy for
      perforated diverticulitis were analysed. Multivariate logistic regression using
      the Mannheim peritonitis index, Colorectal Physiological and Operative Severity
      Score for the enUmeration of Mortality and Morbidity, Charlson comorbidity index
      and Hinchey score was performed to determine the propensity score. RESULTS:
      Patients with HP had significantly higher scores, median age and were more often
      on immunosuppressive medication. Unadjusted logistic regression for outcome
      showed a significant risk of HP vs PA for nonsurgical morbidity (odds ratio 3.25,
      95% CI: 1.26-8.43; P = 0.015), but not for mortality and surgical morbidity.
      After adjusting for the propensity score, outcome was not significantly
      different. Patients with PA had a clinical leak rate of 28% and none of the
      patients with leakage had a protective ileostomy. Patients with PA and leak had
      higher Charlson scores whereas all other scores were similar to nonleak patients.
      CONCLUSION: The theory that PA is generally superior to HP cannot be supported.
      HP remains a safe technique for emergency colectomy in perforated diverticulitis,
      especially in elderly patients with multiple comorbidities. If PA is performed, a
      protective ileostomy must be considered.

PMID- 19175639
TI  - Mortality risk analysis following routine vs selective defunctioning stoma
      formation after total mesorectal excision for rectal cancer.
AB  - OBJECTIVE: To answer the question whether a defunctioning stoma (DS) should be
      constructed routinely after total mesorectal excision or whether it could be used
      selectively to ensure patient safety. METHOD: A PubMed search was performed. All
      randomized trials on the role of a DS were included. Also, observational articles
      published between January 1997 and August 2007 were reviewed. Sensitivity
      analysis of the mortality risk was performed. RESULTS: The clinical anastamotic
      leak (CAL) rate was 17% in 358 patients from four randomized trials and 9.6% in
      4059 patients from 39 observational studies. The CAL rate increased significantly
      from 9.6% with DS to 24.4% without DS in four randomized trials, and from 7.9%
      with DS to 13.2% without DS in 17 observational studies. The re-operation rate as
      a result of anastomotic leakage was lower in patients with DS than in patients
      without DS in both study types. Leak-related mortality was not significantly
      different: 7.2% with vs 7.7% without DS in observational studies, and 0% with vs
      4.6% without DS in randomized trials. Sensitivity analysis indicated that a
      selective DS strategy is acceptable if the CAL rate without DS is less than 16.6%
      with a CAL-related mortality of no more than 4.6%. CONCLUSION: The results of
      this review support the routine construction of a protective stoma. However,
      selective use of a DS is justified from a patient safety point of view if the CAL
      rate and its related mortality are limited. Each unit should audit its
      performance.

PMID- 19175640
TI  - Colonoscopy for 'cryptogenic' pyogenic liver abscess?

PMID- 19175641
TI  - Colonic volvulus--an old problem with a new twist.
AB  - We present a case report involving an unusual type of volvulus. A 51-year-old man
      presented with an acute abdomen. He underwent emergency laparotomy at which we
      identified a volvulus involving his caecum to descending colon in continuity. We
      believe this to be first reported case of total colonic volvulus.

PMID- 19175642
TI  - Morbidity and complications of protective loop ileostomy.
AB  - OBJECTIVE: The creation of a loop ileostomy is considered suitable to protect a
      distal anastomosis in colorectal surgery. This technique is, however, associated
      with failure, complications and even mortality. The aim of this study was to
      quantify retrospectively the morbidity associated with an ileostomy and its
      subsequent closure. METHOD: One hundred and nineteen patients with a temporary
      loop ileostomy, created between January 2000 and July 2007 were retrospectively
      analysed from a review of patient records. RESULTS: All ileostomies were closed
      after a median period of 106 days (interquartile range: 69-174 days). Stoma
      related morbidity occurred in 23 (19%) patients. After ileostomy closure, 16
      major complications were seen in 14 (12%) patients and 43 minor complications
      occurred in 25 (21%) patients. Sixty-three patients (53%) had neither stoma
      related morbidity or peri- or postoperative complications after stoma closure.
      CONCLUSION: Protective loop ileostomy was found to be associated with a high
      morbidity. This raises the question of the mode of identifying the specific
      patients with a low anastomosis who should be provided an ileostomy for
      protection, set against the potential complications of the formation and closure
      of the ileostomy.

PMID- 19175644
TI  - Assessment of sonographic quality of anal sphincter muscles in patients with
      faecal incontinence.
AB  - OBJECTIVE: The main application of endoanal ultrasonography (US) in evaluation of
      faecal incontinence is to identify surgically correctable sphincter defects. The
      aim of our study was to determine whether qualitative changes in echogenicity and
      in uniformity of internal (IAS) and external (EAS) anal sphincter muscles
      detected on endoanal US correlate with other anal laboratory tests and modified
      Wexner faecal incontinence functional score. METHOD: Records on 99 patients
      having complete information on anorectal manometry, faecal incontinence scoring
      and available endoanal US imaging of the anal sphincters were included in
      statistical analysis. Anatomic appearance and changes in echogenicity of the anal
      sphincter muscles were recorded according to the proposed scoring system.
      Endoanal US defect and quality component scores for IAS and EAS as well as the
      total score were correlated with anal laboratory tests and incontinence score
      using Spearman's correlations test. RESULTS: There was a trend for correlation
      between IAS quality score and incontinence score (P = 0.06), but no correlation
      for IAS defect score. EAS defect score had a significant negative correlation
      with maximum squeeze pressure (MSP) (P = 0.031). Distal EAS quality score had a
      significant correlation with incontinence score (P = 0.002). EAS total score
      correlated with MSP (P = 0.02) and incontinence score (P = 0.006). Endoanal US
      total score was significantly correlated with incontinence score (P = 0.006),
      maximal resting (MRP) (P = 0.035) and MSP (P = 0.045) and high pressure anal
      canal zone length (P = 0.03). CONCLUSION: Sonographic morphology of anal
      sphincter muscles correlates with anal laboratory tests and functional
      incontinence score. Qualitative ultrasound scoring instrument may improve
      evaluation of patients with faecal incontinence.

PMID- 19175645
TI  - Anatomical branches of the superior rectal artery in the distal rectum.
AB  - OBJECTIVE: The aim of this experimental study was to study the arterial supply of
      the corpus cavernosum recti in the inner wall of the distal rectum in relation to
      haemorrhoidal ligation therapy. METHOD: In 10 nonfixed human cadavers, the
      arterial vasculature of the rectum was studied using the Araldite casting method.
      Subsequently, the specimens were treated with methylbenzoate in order to obtain
      semitransparent specimens in which the corpus cavernosum recti could be studied.
      RESULTS: Specimens were obtained permitting study of the arterial vasculature of
      the rectum and corpus cavernosum recti at all levels. The superior rectal artery
      was found to supply the corpus cavernosum recti which consisted of a variable
      number of equally spaced twisting arteries. CONCLUSION: The distal rectum is
      supplied by the superior rectal artery. The supplying arteries of the corpus
      cavernosum recti are not confined to the strict locations described in the
      literature. This finding is of importance in surgical treatment of haemorrhoidal
      disease.

PMID- 19175646
TI  - Anastomotic leakage after resection of colorectal cancer generates prodigious use
      of hospital resources.
AB  - OBJECTIVE: The aim of this study was to determine the demand for hospital
      resources generated by anastomotic leakage, including surgical, medical, imaging,
      pathology, and other allied health consultations or services and length of
      postoperative hospital stay. METHOD: Data were obtained from a comprehensive,
      prospective hospital registry of all resections for colorectal cancer from
      January 1995 to December 2004 and from retrospective review of patients' notes.
      RESULTS: Forty-one patients with a leak spent 92 days in intensive care, required
      129 days of total parenteral nutrition, 69 days of enteric feeding and 41 days on
      ventilation and had a median postoperative hospital stay of 28 days (range 11
      104). These patients required 24 re-operations and 2273 separate medical
      consultations or allied services. CONCLUSION: Anastomotic leakage generates a
      very considerable demand for hospital resources and diverts these resources from
      the hospital population at large.

PMID- 19175647
TI  - Restorative proctocolectomy. Does ethnicity affect outcome?
AB  - OBJECTIVE: Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis
      (IPAA) is well-established in the management of ulcerative colitis (UC) and
      familial adenomatous polyposis (FAP). We review outcome of pouch surgery from a
      single centre, comparing non-South Asian and South Asian Caucasian populations.
      METHOD: Patients undergoing RPC for UC and FAP during a 10-year period between
      January 1997 and January 2007 were identified from hospital records. Data were
      collected retrospectively from case notes on early and long-term results.
      RESULTS: A total of 107 patients underwent pouch formation for UC (94%) or FAP
      (6%) and 22 (21%) were from the Asian subcontinent. Eighty-seven (81%) underwent
      a three-stage procedure and 20 (19%) a two-stage procedure. Postoperative
      complications occurred in 40 (37%) patients, being major in 11 (10%) patients
      with relaparotomy required in 9 (8%) with no difference between South Asian and
      non-South Asian Caucasian patients. Long-term pouch function, with a median of
      five times over 24 h (range 2-15), was similar between the two groups. The
      incidence of pouchitis was 57 (53%) and this was significantly greater in the
      South Asian population [17/21 (77%); 39/86 (46%); P = 0.006]. CONCLUSION:
      Surgical results were similar in South Asian and non-South Asian Caucasian
      patients, but the incidence of pouchitis was greater in the former group.

PMID- 19175648
TI  - Perforated phlebosclerotic colitis--description of a case and review of this
      condition.

PMID- 19175649
TI  - Haemorrhoidal artery ligation operation for the treatment of symptomatic
      anorectal varices.

PMID- 19175650
TI  - Inflammatory myofibroblastic tumour of the caecum.

PMID- 19175651
TI  - Review of 120 anal cancer patients.
AB  - OBJECTIVE: Chemoradiotherapy is the mainstay of treatment for the majority of
      patients with anal cancer, with abdominoperineal resection reserved for salvage.
      The purpose of this study was to evaluate our results after radiotherapy with or
      without chemotherapy, and/or surgery in terms of overall survival and colostomy
      free survival in patients with anal cancer. METHOD: A review of patients
      diagnosed with anal cancer between 1991 and 2004 was performed. The principle end
      points of the study were overall and colostomy-free survival. RESULTS: One
      hundred and twenty patients were identified. The T stage distribution was T1 32,
      T2 44, T3 19, T4 17 and TX 8. Eighteen patients had clinically involved regional
      nodes. Eighty patients received radiotherapy as a component of their treatment.
      Twenty-four of the 80 patients had a colostomy. The most common late toxicity was
      faecal incontinence. The overall survival and colostomy-free survival rates for
      all 120 patients were 58% and 79% at 5 years, respectively. For the 80 patients
      who received radiotherapy, the corresponding figures were 66% and 82% at 5 years,
      respectively. CONCLUSION: Chemoradiation is effective organ preserving treatment
      for anal cancer. Grade 1 and 2 faecal incontinence is a relatively common late
      toxicity experienced by patients.

PMID- 19175652
TI  - Rectal bleeding: epidemiology, associated risk factors, and health care seeking
      behaviour: a population-based study.
AB  - PURPOSE: Rectal bleeding is considered an important sign of colonic disease,
      particularly colorectal cancer. The epidemiology of rectal bleeding in the
      community is poorly understood. Moreover, there is little information as to
      whether individuals seek health care for this problem. This study aimed to
      determine the prevalence of rectal bleeding and levels of healthcare seeking
      amongst an Australian population. METHOD: A community sample of adults aged above
      18 years of Penrith (a Sydney suburb representative of the Australian population)
      selected randomly from the electoral roll. The survey consisted of a self
      administered questionnaire sent out to 440 residents stratified for equal numbers
      of men and women. RESULTS: The response rate was 77% (n = 338; mean age 46 years;
      SD: 16; range: 18-90; 55% women). Blood in the stools in the previous 12 months
      was reported by 18% (95% CI: 14-23). Colour of the blood in bowel movements was
      reported as bright (72%), dark (7%), bright and dark (10%), 11% did not know.
      Only 31% (n = 21/68) of respondents with rectal bleeding had visited a physician
      primarily about the presence of blood in the bowel movement within the previous
      12 months. The majority (90%) who consulted about the presence of blood were aged
      between 30 and 60 years. Blood in the stools was independently associated with
      younger age (OR = 0.97, 95% CI: 0.95-0.99, P = 0.01), feelings of incomplete
      rectal evacuation (OR = 3.42, 95% CI: 1.66-7.08, P = 0.001), self-reported injury
      or tear (OR = 3.45, 95% CI: 1.53-7.69, P = 0.002), and surgery (OR = 2.70, 95%
      CI: 1.03-7.14, P = 0.04) to the perianal region. CONCLUSIONS: Rectal bleeding is
      common in the general population. Only one-third of those with rectal bleeding
      consults a physician about their condition. Rectal bleeding occurs in younger
      individuals, those who suffer from incomplete evacuation and among individuals
      who have had an injury, tear or surgery to the anus.

PMID- 19175653
TI  - Quality of mesorectum after laparoscopic resection for rectal cancer - results of
      an audited teaching programme in Spain.
AB  - OBJECTIVE: The aim of this prospective observational study was to compare the
      quality of total mesorectal excision between laparoscopic and open surgery for
      rectal cancer. METHOD: In April 2006, the Spanish Association of Surgeons started
      an audited teaching programme. The project was similar to the Norwegian one and
      several training courses were arranged. Patients were classified into two groups:
      laparoscopic rectal resection (LR) and open rectal resection (OR). The quality of
      the mesorectum was scored: complete, nearly complete or incomplete. The
      circumferential margin (CRM) was considered positive, if tumour was located 1 mm
      or less from the surface of the specimen. RESULTS: Between 2006 and 2008, 604
      patients underwent rectal resection with total mesorectal excision for rectal
      cancer: 209 patients were included in the LR group and 395 patients in the OR
      group. There were no differences in terms of number of lymph nodes affected,
      distance of the tumour from CRM. The mesorectum was complete in 464 (76.8%),
      nearly complete in 91 (15.1%) and incomplete in 49 patients (8.1%). CRM was
      negative in 534 patients (88.4%). No differences were observed between the two
      groups. The overall postoperative morbidity rate was 38.8% in LR group and 44.6%
      in OR group (P = 0.170). Overall postoperative mortality rate was 2.5%. One
      patient died (0.5%) in the LR group and 14 patients died (3.5%) in the OR group
      (P = 0.021). CONCLUSION: Laparoscopic resection for rectal cancer is feasible
      with the quality of mesorectal excision and postoperative outcomes similar to
      those of open surgery.

PMID- 19175654
TI  - The creation of a peritoneal defect in transanal endoscopic microsurgery does not
      increase complications.
AB  - INTRODUCTION: During Transanal Endoscopic Microsurgical (TEMS) full-thickness
      excision of a rectal lesion above the peritoneal reflection, entrance to the
      peritoneal cavity is inevitable. This has been regarded as a complication that
      requires conversion to an open procedure. We describe our experience of full
      thickness intraperitoneal excision of rectal lesions where the peritoneal defect
      was sutured endoscopically. METHOD: Data were collected prospectively on 15
      patients in whom a peritoneal defect was created intraoperatively during TEMS
      excision of a rectal lesion. When a defect was recognized, it was closed by
      endoscopic suture. If there was any doubt regarding security of the closure, a
      defunctioning loop stoma was fashioned. RESULTS: Between November 1998 and
      January 2008, a total of 257 patients underwent TEMS during which a peritoneal
      defect was created in 15 patients. Six patients had a defunctioning stoma formed
      at the time of TEMS. No patient was defunctioned postoperatively and there were
      no deaths. The mean hospital stay was 8 days (range 3 to 19 days). A contrast
      enema showed sub-clinical leaks in two patients for which no treatment was
      required. No patient developed pelvic or peritoneal sepsis, but one patient had
      to return to theatre for postoperative bleeding when a single bleeding vessel was
      coagulated. CONCLUSION: Full thickness excision of lesions in the intraperitoneal
      rectum with endoscopic suture of the defect is a safe procedure. Lesions in the
      upper rectum should not be excluded from TEMS excision because of the chance of
      peritoneal breach.

PMID- 19175655
TI  - Growth pattern in the muscular layer reflects the biological behaviour of
      colorectal cancer.
AB  - OBJECTIVE: To determine the clinical value of evaluating the cancer morphology in
      muscularis propria (MP) for colorectal cancer (CRC) patients. METHOD: A total of
      994 patients with advanced CRC were reviewed in terms of two distinctive growth
      patterns in the MP: (i) horizontal spread between the circular and longitudinal
      muscle layers (H-spread) and (ii) 'streaming' spread between the muscle bundles
      of the circular muscle layer (S-spread). RESULTS: The incidence of H-spread (n =
      153) and S-spread (n = 150) showed a positive correlation with tumour-node
      metastasis (TNM) stage and both exerted a negative impact on postoperative
      survival. Adverse morphology in the MP (H-spread and/or S-spread) was consistent
      with a high grade of vascular invasion and budding in the extramural layer, as
      also with unfavourable fibrotic stromas in the reactive fibrous zone; the 5-year
      survival rate in patients with such features was 64.2%, which was lower than that
      in those without (86.5%, P < 0.0001). Multivariate analysis demonstrated that
      adverse morphology was an independent prognostic determinant, along with T- and N
      -stage. As the mode of H-spread, perineural invasion in the myenteric plexus was
      found to be predominant over lymphatic spread on the basis of S100 and CD34
      immunostaining, but neural cell adhesion molecule expression, whether on cancer
      cells or on neural cells, was not significant for this growth pattern.
      CONCLUSION: A particular group of CRCs ingeniously utilizes the thin space
      between muscle fascicles for development in the MP. Although the biological
      mechanism remains unknown, this distinctive growth pattern could be a useful
      indicator to identify CRC patients at high risk of recurrence.

PMID- 19175656
TI  - Physiological, psychological and behavioural characteristics of men and women
      with faecal incontinence.
AB  - BACKGROUND: The factors leading to faecal incontinence in males are less well
      understood than those in females. In this prospective study we aimed to compare
      the physiological, anatomical, psychological and behavioural characteristics of
      male and female patients presenting with symptoms of faecal incontinence. METHOD:
      One hundred and nine patients presenting with symptoms of faecal incontinence
      were studied. They underwent anorectal physiological studies, endoanal
      ultrasonography, and completed a St Mark's Incontinence Score, a locally
      developed pad questionnaire, a bowel symptom questionnaire, the Short Form 36 (SF
      36) Health Survey questionnaire, the Hospital Anxiety and Depression Scale and
      the Maudsley Obsessive Compulsive Inventory. RESULTS: Thirty-four men (mean age
      59 years, SD 14 years, range 33-80) and 75 women (mean age 55 years, SD 15 years,
      range 21-86) participated in the study. Twenty-one patients (38% of men and 11%
      of women) had normal manometry and endoanal ultrasonography. There was no
      significant difference in the resting pressures of men compared with women, but
      men had significantly higher squeeze pressures. Rectal capacity was significantly
      higher in men but anal and rectal electrosensitivities were the same. Men placed
      a tissue at the anus more commonly than women while women were more likely to use
      a pad and to carry a spare pair of underwear around with them. Psychological
      profiles were very similar in the two sexes. CONCLUSIONS: Nearly 40% of men with
      faecal incontinence report it in the absence of a definable functional or
      structural sphincter abnormality. There are differences in physiological
      characteristics and coping behaviours of men and women with faecal incontinence.

PMID- 19175657
TI  - Current practice in the United Kingdom for the use of diagnostic laparoscopy in
      suspected acute appendicitis.
AB  - OBJECTIVE: Diagnostic laparoscopy is advocated in the management of patients with
      acute right iliac fossa pain. We asked consultant surgeons in the UK about their
      current use of this technique. METHOD: A short anonymous questionnaire was sent
      to consultant surgeons from the ASGBI database. Information was sought on general
      surgical specialty, participation in the emergency surgical on-call rota, current
      practice regarding the use of diagnostic laparoscopy in patients with suspected
      acute appendicitis and on the management of an inflamed or noninflamed appendix.
      Statistical analysis was by means of chi(2) test. RESULTS: There were 161
      eligible returns from 250 questionnaires (64%) and the proportion of consultants
      replying from each subspecialty was similar to membership numbers of subspecialty
      organizations. Most consultants (68%) performed diagnostic laparoscopy in
      patients with suspected acute appendicitis. The majority (69%) reserved its use
      for women of reproductive age and 14% of respondents laparoscoped all patients
      with suspected appendicitis. Compared to nongastrointestinal (GI), GI surgeons
      were significantly more likely to perform diagnostic laparoscopy (75 vs 52%, P =
      0.008). In the case of an overtly inflamed appendix, 81% of respondents would
      remove it laparoscopically with significantly more GI surgeons following this
      course than nonGI surgeons (P = 0.04). CONCLUSION: Despite good evidence on the
      benefits of diagnostic laparoscopy in certain patients with suspected acute
      appendicitis, there is significant variation in its use. This difference appears
      to be based upon subspecialty and may be as a result of increasing
      subspecialization.

PMID- 19175658
TI  - Split-shot sinker facilitates seton treatment of anal fistulae.
AB  - OBJECTIVE: The cutting seton is an inexpensive and effective method of treating
      high complex perianal fistulae. Following placement of the seton, advancement
      through the external sphincter muscles requires progressive tightening of the
      seton. The requirement for maintaining the appropriate tension and onset of
      perianal pressure necrosis are problems frequently encountered using this
      technique. METHOD: Using a 3-0 polypropylene suture, a red-rubber catheter, and a
      nontoxic tin split-shot sinker, we minimized or eliminated these problems.
      RESULTS: We initially used this technique in one patient with satisfactory
      results. CONCLUSION: This technique is technically easy, safe, inexpensive, and
      efficient, and we are using it in all patients with high perianal fistulae who
      require a seton.

PMID- 19175659
TI  - Impact of oral disease on quality of life in the US and Australian populations.
AB  - The US National Health and Nutrition Examination Survey (NHANES 2003-2004)
      evaluated oral health quality of life for the first time using a previously
      untested subset of seven Oral Health Impact Profile (OHIP) questions, i.e. the
      NHANES-OHIP. OBJECTIVES: (i) To describe the impact of dental conditions on
      quality of life in the US adult population; (ii) to evaluate construct validity
      and adequacy of the NHANES-OHIP in NHANES 2003-2004 and a comparable Australian
      survey. METHODS: In the cross-sectional NHANES 2003-2004 survey of a nationally
      representative sample of US adults (n=4907), prevalence was quantified as the
      proportion of adults who reported experiencing one or more impacts fairly often
      or very often within the past year. Construct validity was tested by comparing
      prevalence estimates across categories of sociodemographic, dental health and
      utilization characteristics known to vary in oral health. In 2002, Australian
      cross-sectional survey of a nationally representative sample of adults (n=2644),
      adequacy of the NHANES-OHIP questions were tested with reference to a slightly
      modified version of the OHIP-14 questions. RESULTS: NHANES-OHIP prevalence
      estimates were markedly similar in the United States (15.3%) and Australia
      (15.7%). In the US construct, validity was evidenced by higher NHANES-OHIP scores
      among groups with greater levels of tooth loss, perceived treatment need and
      problem-oriented visiting and with lack of private dental insurance and low
      income. In Australia, prevalence for the NHANES-OHIP closely resembled prevalence
      estimates of the modified OHIP-14. Both varied to a similar degree across levels
      of tooth loss, perceived treatment need, problem-oriented visiting, and private
      dental insurance and income, demonstrating adequacy of the NHANES-OHIP as a brief
      independent instrument. CONCLUSIONS: There was acceptable construct validity and
      adequacy of the NHANES-OHIP questionnaire. In the United States, the impact of
      oral disease disproportionately affected disadvantaged groups, a finding that
      supports application of the US Healthy People 2010 major goals of improved
      quality of life and reduced health disparities.

PMID- 19175660
TI  - Comparison of the discriminative ability of the generic and condition-specific
      forms of the Child-OIDP index: a study on children with different types of
      normative dental treatment needs.
AB  - OBJECTIVE: To compare the discriminative ability of the Generic and Condition
      Specific forms of the Child-OIDP index on groups defined by their normative
      treatment need for dental caries, periodontal disease, malocclusion and traumatic
      dental injuries. METHODS: All 1034 11-12-year-old children were included from all
      the primary schools in a municipal area of Suphanburi Province, Thailand.
      Children were interviewed about sociodental impacts on quality of life in the
      past 3 months using the Child-OIDP index, and then clinically examined to assess
      their normative treatment need for dental caries, periodontal disease,
      malocclusion and traumatic dental injuries. Discriminative ability of the Generic
      and the Condition-Specific Child-OIDP (CS-Child-OIDP) was assessed through
      differences in overall scores and prevalences of oral impacts between groups, as
      well as through their respective effect sizes and adjusted Odds Ratios (ORs).
      RESULTS: Differences in overall scores and prevalences of oral impacts between
      groups with and without each of the four types of normative dental treatment
      needs, their corresponding effect sizes and adjusted ORs, were always significant
      for CS-Child-OIDP. However, when the Generic Child-OIDP was used to discriminate
      between groups, the respective figures were significant only for groups with and
      without normative treatment need for dental caries. CONCLUSIONS: CS-Child-OIDP
      was better able to discriminate between groups with and without each of the four
      types of normative dental treatment need. The better performance of CS-Child-OIDP
      compared with the generic Child-OIDP was independent of the indicator used to
      assess discriminative ability (i.e. differences between groups, effect sizes or
      adjusted ORs).

PMID- 19175661
TI  - Factors influencing caries experience among adults with physical and intellectual
      disabilities.
AB  - BACKGROUND: There is limited and inconsistent evidence on the influence of
      residential setting on caries experience of adults with physical and intellectual
      disabilities (PID), described here as care-recipients. OBJECTIVE: To examine
      caries experience and associated factors among adults with PID. METHODS: Mailed
      questionnaire survey (2005-2006) of carers of adults with PID (18-44 years) in
      South Australia from family homes, community housing, and institutions, and oral
      examinations of care-recipients recording decayed (D), missing (M) and filled (F)
      teeth (DMFT). RESULTS: Carers completed questionnaires for 485 care-recipients,
      267 of whom were examined (completion rate=55.1%). The prevalence of decay (D>0)
      was 16.9% and 76.3% had caries experience (DMFT>0). In unadjusted analysis, care
      recipients at institutions had a significantly higher mean DMFT than other
      settings. After adjusting for carer and care-recipient characteristics, there was
      no difference in any of the DMFT components among residential settings. However,
      there were statistically significant associations (OR+/-95% CI excluding unity)
      between decayed teeth and moderate and high intake of sweet drinks and frequency
      of dental visits. Higher odds of missing teeth were associated with type of
      disability, general anaesthetic requirement for dental treatment and low and high
      carer-contact. Higher odds of filled teeth were associated with age, no oral
      hygiene assistance (OHA) and high carer-contact. Higher odds of caries experience
      were associated with age and no OHA. CONCLUSIONS: Residential setting was not
      associated with caries experience. Modifiable risk factors were diet, frequency
      of dental visits, no OHA and carer-contact hours.

PMID- 19175662
TI  - Recent changes in the workforce and practice of dermatologic surgery.
AB  - BACKGROUND: The increasing number of American College of Mohs Surgery (ACMS)
      fellowship positions over the last decade has resulted in a greater number of
      fellowship-trained surgeons in dermatologic surgery. METHODS: Mohs micrographic
      fellowship-trained surgeons (MMFTSs) and non-Mohs fellowship-trained surgeons
      performing Mohs micrographic surgery (NMMFTSs) were compared using the American
      Academy of Dermatology Practice Profile Survey (2002/05). An analysis of recent
      Mohs fellowship classes was also performed. RESULTS: In 2005, there was an
      equivalent proportion of MMFTSs and NMMFTSs in the workforce (ratio
      MMFTS:NMMFTS=0.9) but, in 2005, there was a shift in the youngest age cohort (29
      39) to a greater proportion of MMFTSs (MMFTS:NMMFTS=1.55). In 2005, the youngest
      MMFTSs (29-39) were more likely to be female (47.1%) than of MMFTSs overall
      (24%). MMFTSs were 5 times as likely to be in full-time academic positions and
      performed 2 to 3 times as many Mohs cases per week as NMMFTSs. CONCLUSIONS:
      Consistent with demographic shifts in dermatology, differences have emerged in
      the demographics, surgical volumes, and settings of MMFTSs and NMMFTSs. Recent
      increases in the ACMS fellowship positions have resulted in a greater proportion
      of MMFTSs among younger dermatologic surgeons. It will be important to follow how
      this increase in fellowship trainees affects the dermatologic surgery workforce.

PMID- 19175663
TI  - The importance of reviewing pathology specimens before Mohs surgery.
AB  - BACKGROUND: The review of outside biopsy slides before performing surgery is the
      standard of care in many surgical specialties. Previous studies have shown high
      discrepancy rates between the original and second-opinion diagnoses. The
      frequency with which this practice changes the diagnosis and management of
      patients undergoing Mohs surgery is undocumented in the literature. It is
      standard practice at our institution to review all outside biopsy slides before
      Mohs surgery. OBJECTIVE: To investigate how often review of outside biopsies by
      an internal dermatopathologist changes patients' initial referral diagnosis and
      subsequent management. METHODS & MATERIALS: This is a retrospective review of all
      patients referred to Mohs surgery from January 2003 through March 2007. The
      number of cases in which the diagnosis changed and how this change affected
      management were recorded. RESULTS: Seventy-four of 3,345 (2.2%) cases were
      identified in which the diagnosis changed after review of the biopsy slides.
      Management was affected in the majority (61%) of cases. Board-certified
      dermatopathologists originally read nearly half of the biopsies. CONCLUSION:
      Review of outside biopsy slides before surgery can change the diagnosis in a
      large proportion of patients, with a resulting change in management. This quality
      assurance practice may improve patient care.

PMID- 19175664
TI  - Prevalence of methicillin-resistant Staphylococcus aureus in the setting of
      dermatologic surgery.
AB  - BACKGROUND: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA)
      in the postoperative setting of dermatologic surgery is unknown. Such data could
      influence the empirical treatment of suspected infections. OBJECTIVE: To examine
      the period prevalence of MRSA infections in the postoperative setting of
      dermatologic surgery. METHODS: We performed chart reviews of 70 patients who had
      bacterial cultures taken from January 2007 to December 2007. In the 21
      postsurgical cases, we analyzed age, risk factors, sites of predilection, method
      of repair, and pathogen of growth. RESULTS: The mean age of the overall study
      population was 57, with the mean age of postsurgical MRSA-positive cases being
      75.5. Of the 21 postsurgical cultures taken, 16 cultures grew pathogen, and two
      of the 16 (13%) pathogen-positive cultures grew MRSA. LIMITATIONS: This is a
      retrospective chart review of a relatively small sample size in one geographic
      location. Our patient population is known to contain a large number of retirees.
      CONCLUSION: The increasing prevalence of MRSA skin and soft tissue infections and
      recommendation to modify empirical antibiotic therapy have been well documented
      in particular patient populations, but we caution against the empirical use of
      MRSA-sensitive antibiotics in the postoperative setting of dermatologic surgery.
      We advocate culturing all infectious lesions upon presentation and reserve
      empirical use of MRSA-sensitive antibiotics for high-risk patients or locations.

PMID- 19175665
TI  - Carrying photosynthesis genes increases ecological fitness of cyanophage in
      silico.
AB  - Several viruses infecting marine cyanobacteria carry photosynthesis genes (e.g.
      psbA, hli) that are expressed, yield proteins (D1, HLIP) and help maintain the
      cell's photosynthesis apparatus during the latent period. This increases energy
      and speeds up virus production, allowing for a reduced latent period (a fitness
      benefit), but it also increases the DNA size, which slows down new virus
      production and reduces burst size (a fitness cost). How do these genes affect the
      net ecological fitness of the virus? Here, this question is explored using a
      combined systems biology and systems ecology ('systems bioecology') approach. A
      novel agent-based model simulates individual cyanobacteria cells and virus
      particles, each with their own genes, transcripts, proteins and other properties.
      The effect of D1 and HLIP proteins is explicitly considered using a mechanistic
      photosynthesis component. The model is calibrated to the available database for
      Prochlorococcus ecotype MED4 and podovirus P-SSP7. Laboratory- and field-scale in
      silico survival, competition and evolution (gene packaging error) experiments
      with wild type and genetically engineered viruses are performed to develop
      vertical survival and fitness profiles, and to determine the optimal gene
      content. The results suggest that photosynthesis genes are nonessential, increase
      fitness in a manner correlated with irradiance, and that the wild type has an
      optimal gene content.

PMID- 19175666
TI  - Tobacco-induced alterations to Porphyromonas gingivalis-host interactions.
AB  - Smokers are more susceptible than non-smokers to persistent infection by
      Porphyromonas gingivalis, a causative agent of periodontitis. Patients who smoke
      exhibit increased susceptibility to periodontitis and are more likely to display
      severe disease and be refractory to treatment. Paradoxically, smokers demonstrate
      reduced clinical inflammation. We show that P. gingivalis cells exposed to
      cigarette smoke extract (CSE) induce a lower proinflammatory response (tumour
      necrosis factor-alpha, interleukin-6, interleukin-12 p40) from monocytes and
      peripheral blood mononuclear cells than do unexposed bacteria. This effect is
      reversed when CSE-exposed bacteria are subcultured in fresh medium without CSE.
      Using microarrays representative of the P. gingivalis genome, CSE-exposure
      resulted in differential regulation of 6.8% of P. gingivalis genes, including
      detoxification and oxidative stress-related genes; DNA repair genes; and multiple
      genes related to P. gingivalis virulence, including genes in the major fimbrial
      and capsular operons. Exposure to CSE also altered the expression of outer
      membrane proteins, most notably by inducing the virulence factors RagA and RagB,
      and a putative lipoprotein cotranscribed with the minor fimbrial antigen.
      Therefore, CSE represents an environmental stress to which P. gingivalis adapts
      by altering gene expression and outer membrane proteins. These changes may
      explain, in part, the altered virulence and host-pathogen interactions that have
      been documented in vivo in smokers with periodontal disease.

PMID- 19175667
TI  - Characterization of cellulose production in Escherichia coli Nissle 1917 and its
      biological consequences.
AB  - Bacterial species of the Enterobacteriaceae family produce cellulose and curli
      fimbriae as extracellular matrix components, and their synthesis is positively
      regulated by the transcriptional activator CsgD. In this group of bacteria,
      cellulose biosynthesis is commonly regulated by CsgD via the GGDEF domain protein
      AdrA, a diguanylate cyclase that produces cyclic-diguanylic acid (c-di-GMP), an
      allosteric activator of cellulose synthase. In the probiotic Escherichia coli
      strain Nissle 1917 and its recent clonal isolates, CsgD activates the production
      of curli fimbriae at 28 degrees C, but neither CsgD nor AdrA is required for the
      c-di-GMP-dependent biosynthesis of cellulose at 28 degrees C and 37 degrees C. In
      these strains, the GGDEF domain protein YedQ, a diguanylate cyclase that
      activates cellulose biosynthesis in certain E. coli strains, is not required for
      cellulose biosynthesis and it has in fact evolved into a novel protein. Cellulose
      production in Nissle 1917 is required for adhesion of bacteria to the
      gastrointestinal epithelial cell line HT-29, to the mouse epithelium in vivo, and
      for enhanced cytokine production. The role of cellulose in this strain is in
      contrast to the role of cellulose in the commensal strain E. coli TOB1.
      Consequently, the role of cellulose in bacterial-host interaction is dependent on
      the E. coli strain background.

PMID- 19175669
TI  - Analysis of the elderly patient population in a tertiary-care university
      hospital.
AB  - A progressively ageing population and the high association between advanced age
      and cancer has resulted in an increased interest in the field of geriatric
      oncology with the objective being a more effective diagnosis and treatment of
      these patients. We performed an epidemiological analysis on an intent-to-treat of
      elderly population within our healthcare unit. This is a retrospective study of
      all patients attended in our Medical Oncology Department during the year 2002. A
      total 667 patients were assessed, 42% older than 70 years of age. The most
      frequent tumour sites were lung, colorectal and breast. The most frequent
      histology was adenocarcinoma. The diagnosis in advanced stages was significantly
      higher in older age group (76% vs. 59%). The use of symptom-control follow-up and
      palliative-care, compared with radio- and chemo-therapy, was higher in older age
      group. However, we observed no statistically significant differences with respect
      to inclusion in clinical trials. In conclusion, the elderly represents an
      important percentage of patients receiving cancer care. The distributions by
      sites and histology types are similar in both groups of age. Although the
      election of palliative treatment is more frequent in elderly population, the most
      frequently used treatments in both groups, were radiotherapy and chemotherapy. We
      didn't observe any significant differences about the inclusion in clinical
      trials.

PMID- 19175668
TI  - Hippocampal zinc infusion delays the development of afterdischarges and seizures
      in a kindling model of epilepsy.
AB  - PURPOSE: Zinc occurs in high concentration in synaptic vesicles of glutamatergic
      terminals including hippocampal mossy fibers. This vesicular zinc can be
      synaptically released during neuronal activity, including seizures. Zinc inhibits
      certain subtypes of N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid
      (GABA)(A) receptors. By blocking NMDA excitation or GABA inhibition, an excess of
      zinc may alter the excitability of hippocampal circuits, which contribute to the
      development of seizures. METHODS: Twenty-one adult Wistar rats were implanted
      under anesthesia with Alzet pumps releasing vehicle, 10 microM ZnCl(2) or 1,000
      microM ZnCl(2), at a rate of 0.25 microl/h continuously into the hippocampal
      hilus for 4 weeks. Kindling was performed by daily awake commissural stimulation
      at 60 Hz and afterdischarges were recorded from a dentate gyrus electrode.
      Development of behavioral Racine seizure stages was recorded by a blinded
      investigator. RESULTS: The development of behavioral Racine seizure stages was
      delayed only in rats infused with 1,000 microM ZnCl(2) (p < 0.02). With
      completion of kindling at stimulation number 20, all groups had reached the same
      maximum level of behavioral seizures. The expected increased progression of
      afterdischarge duration was inhibited by both 10 microM ZnCl(2) and 1,000 microM
      ZnCl(2) infusion compared to control animals (p < 0.01). At stimulation number
      18, all groups had reached the same maximum duration of afterdischarges.
      DISCUSSION: We conclude that excess infused zinc delayed the development of
      behavioral seizures in a kindling model of epilepsy. These data support the
      hypothesis that zinc synaptically released during seizures may alter hippocampal
      excitability similar to zinc infused in our experiment.

PMID- 19175670
TI  - Moving ahead in diabetics' cancer screening; food for thought from the Hellenic
      experience.
AB  - Although data from literature suggest that diabetic women are frequently under
      screened for gynaecological cancers little is known about screening
      implementation for other cancers for both genders. This study investigates
      comprehensive cancer screening practices of diabetics as compared with non
      diabetics; analyses screening patterns both by gender and level of evidence and
      reveals target subgroups that should be paid more attention for screening
      implementation. 675 diabetics vs. 5772 non-diabetic Greek individuals entered the
      PACMeR 02 cancer screening study. Diabetic women reported significantly lower
      performance for the sex-specific evidence-based cancer screening tests and
      digital rectal examination (DRE) as compared with non-diabetics (P < 0.05).
      Diabetic women older than 60 years old, of elementary education, housewives and
      farmers showed the lowest performance rates (P < 0.01). Prostate cancer screening
      was higher among diabetic men with ultrasound and DRE reaching statistical
      significance (P < 0.05). Subgroups analysis did not reveal a hidden relationship.
      Both genders of diabetics reported never performing skin examination at higher
      rates (P < 0.001), although screening intent is extremely low in both diabetics
      and non-diabetics (<1%). Evidence-based screening coverage was inconsistent in
      both genders independently by the diabetic status. Primary care efforts should be
      provided to implement presymptomatic cancer control.

PMID- 19175672
TI  - 'Big frog, small frog'--maintaining proportions in embryonic development:
      delivered on 2 July 2008 at the 33rd FEBS Congress in Athens, Greece.
AB  - We discuss mechanisms that enable the scaling of pattern with size during the
      development of multicellular organisms. Recently, we analyzed scaling in the
      context of the early Xenopus embryo, focusing on the determination of the dorsal
      ventral axis by a gradient of BMP activation. The ability of this system to
      withstand extreme perturbation was exemplified in classical experiments performed
      by Hans Spemann in the early 20th century. Quantitative analysis revealed that
      patterning is governed by a noncanonical 'shuttling-based' mechanism, and defined
      the feedback enabling the scaling of pattern with size. Robust scaling is due to
      molecular implementation of an integral-feedback controller, which adjusts the
      width of the BMP morphogen gradient with the size of the system. We present an
      'expansion-repression' feedback topology which generalizes this concept for a
      wider range of patterning systems, providing a general, and potentially widely
      applicable model for the robust scaling of morphogen gradients with size.

PMID- 19175671
TI  - A facile method for expression and purification of the Alzheimer's disease
      associated amyloid beta-peptide.
AB  - We report the development of a high-level bacterial expression system for the
      Alzheimer's disease-associated amyloid beta-peptide (Abeta), together with a
      scaleable and inexpensive purification procedure. Abeta(1-40) and Abeta(1-42)
      coding sequences together with added ATG codons were cloned directly into a Pet
      vector to facilitate production of Met-Abeta(1-40) and Met-Abeta(1-42), referred
      to as Abeta(M1-40) and Abeta(M1-42), respectively. The expression sequences were
      designed using codons preferred by Escherichia coli, and the two peptides were
      expressed in this host in inclusion bodies. Peptides were purified from inclusion
      bodies using a combination of anion-exchange chromatography and centrifugal
      filtration. The method described requires little specialized equipment and
      provides a facile and inexpensive procedure for production of large amounts of
      very pure Abeta peptides. Recombinant peptides generated using this protocol
      produced amyloid fibrils that were indistinguishable from those formed by
      chemically synthesized Abeta1-40 and Abeta1-42. Formation of fibrils by all
      peptides was concentration-dependent, and exhibited kinetics typical of a
      nucleation-dependent polymerization reaction. Recombinant and synthetic peptides
      exhibited a similar toxic effect on hippocampal neurons, with acute treatment
      causing inhibition of MTT reduction, and chronic treatment resulting in neuritic
      degeneration and cell loss.

PMID- 19175673
TI  - Mitogen-activated protein kinase phosphatase-1 modulated JNK activation is
      critical for apoptosis induced by inhibitor of epidermal growth factor receptor
      tyrosine kinase.
AB  - Alterations resulting in enhanced epidermal growth factor receptor (EGFR)
      expression or function have been documented in a variety of tumors. Therefore,
      EGFR-tyrosine kinase is a promising therapeutic target. Although in vitro and in
      vivo studies have shown the anti-tumor activity of EGFR-tyrosine kinase
      inhibitors against various tumor types, little is known about the mechanism by
      which such inhibitors effect their anti-tumor action. AG1478 is known to
      selectively inhibit EGFR-tyrosine kinase. In this study, we showed that AG1478
      caused apoptosis and apoptosis-related reactions such as the activation of
      caspase 3 in human non-small cell lung cancer cell line PC-9. To investigate the
      signaling route by which AG1478 induced apoptosis, we examined the activation of
      c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase p38 in AG1478
      treated PC-9 cells. JNK, but not p38, was significantly activated by AG1478 as
      determined by both immunoblot analysis for levels of phosphorylated JNK and an in
      vitro activity assay. Various types of stimuli activated JNK through
      phosphorylation by the dual-specificity JNK kinases, but the dual-specificity JNK
      kinases MKK4 and MKK7 were not activated by AG1478 treatment. However, JNK
      phosphatase, i.e. mitogen-activated protein kinase phosphatase-1 (MKP-1), was
      constitutively expressed in the PC-9 cells, and its expression level was reduced
      by AG1478. The inhibition of JNK activation by ectopic expression of MKP-1 or a
      dominant-negative form of JNK strongly suppressed AG1478-induced apoptosis. These
      results reveal that JNK, which is activated through the decrease in the MKP-1
      level, is critical for EGFR-tyrosine kinase inhibitor-induced apoptosis.

PMID- 19175674
TI  - An ecdysteroid-inducible insulin-like growth factor-like peptide regulates adult
      development of the silkmoth Bombyx mori.
AB  - Insulin-like growth factors (IGFs) play essential roles in fetal and postnatal
      growth and development of mammals. They are secreted by a wide variety of
      tissues, with the liver being the major source of circulating IGFs, and regulate
      cell growth, differentiation and survival. IGFs share some biological activities
      with insulin but are secreted in distinct physiological and developmental
      contexts, having specific functions. Although recent analyses of invertebrate
      genomes have revealed the presence of multiple insulin family peptide genes in
      each genome, little is known about functional diversification of the gene
      products. Here we show that a novel insulin family peptide of the silkmoth Bombyx
      mori, which was purified and sequenced from the hemolymph, is more like IGFs than
      like insulin, in contrast to bombyxins, which are previously identified insulin
      like peptides in B. mori. Expression analysis reveals that this IGF-like peptide
      is predominantly produced by the fat body, a functional equivalent of the
      vertebrate liver and adipocytes, and is massively released during pupa-adult
      development. Studies using in vitro tissue culture systems show that secretion of
      the peptide is stimulated by ecdysteroid and that the secreted peptide promotes
      the growth of adult-specific tissues. These observations suggest that this
      peptide is a Bombyx counterpart of vertebrate IGFs and that functionally IGF-like
      peptides may be more ubiquitous in the animal kingdom than previously thought.
      Our results also suggest that the known effects of ecdysteroid on insect adult
      development may be in part mediated by IGF-like peptides.

PMID- 19175675
TI  - Evolutionary divergence of valosin-containing protein/cell division cycle protein
      48 binding interactions among endoplasmic reticulum-associated degradation
      proteins.
AB  - Endoplasmic reticulum (ER)-associated degradation (ERAD) is a cell-autonomous
      process that eliminates large quantities of misfolded, newly synthesized protein,
      and is thus essential for the survival of any basic eukaryotic cell. Accordingly,
      the proteins involved and their interaction partners are well conserved from
      yeast to mammals, and Saccharomyces cerevisiae is widely used as a model system
      with which to investigate this fundamental cellular process. For example, valosin
      containing protein (VCP) and its yeast homologue cell division cycle protein 48
      (Cdc48p), which help to direct polyubiquitinated proteins for proteasome-mediated
      degradation, interact with an equivalent group of ubiquitin ligases in mouse and
      in S. cerevisiae. A conserved structural motif for cofactor binding would
      therefore be expected. We report a VCP-binding motif (VBM) shared by mammalian
      ubiquitin ligase E4b (Ube4b)-ubiquitin fusion degradation protein 2a (Ufd2a),
      hydroxymethylglutaryl reductase degradation protein 1 (Hrd1)-synoviolin and
      ataxin 3, and a related sequence in M(r) 78,000 glycoprotein-Amfr with slightly
      different binding properties, and show that Ube4b and Hrd1 compete for binding to
      the N-terminal domain of VCP. Each of these proteins is involved in ERAD, but
      none has an S. cerevisiae homologue containing the VBM. Some other invertebrate
      model organisms also lack the VBM in one or more of these proteins, in contrast
      to vertebrates, where the VBM is widely conserved. Thus, consistent with their
      importance in ERAD, evolution has developed at least two ways to bring these
      proteins together with VCP-Cdc48p. However, the differing molecular architecture
      of VCP-Cdc48p complexes indicates a key point of divergence in the molecular
      details of ERAD mechanisms.

PMID- 19175677
TI  - Spatial and temporal variability in a stratified hypersaline microbial mat
      community.
AB  - Hypersaline microbial mat communities have recently been shown to be more diverse
      than once thought. The variability in community composition of hypersaline mats,
      both in terms of spatial and temporal dimensions, is still poorly understood.
      Because this information is essential to understanding the complex biotic and
      abiotic interactions within these communities, terminal restriction fragment
      analysis and 16S rRNA gene sequencing were used to characterize the near-surface
      community of a hypersaline microbial mat in Guerrero Negro, Mexico. Core samples
      were analyzed to assay community variability over large regional scales
      (centimeter to kilometer) and to track depth-related changes in population
      distribution at 250-microm intervals over a diel period. Significant changes in
      total species diversity were observed at increasing distances across the mat
      surface; however, key species (e.g. Microcoleus sp.) were identified throughout
      the mat. The vertical position and abundance of >50% of the 60 peaks detected
      varied dramatically over a diel cycle, including Beggiatoa sp., cyanobacteria,
      Chloroflexus sp., Halochromatium sp., Bacteroidetes sp. and several as-yet
      identified bacteria. Many of these migrations correlated strongly with diel
      changes in redox conditions within the mat, contributing to strong day-night
      community structure differences.

PMID- 19175678
TI  - Facilitated establishment of Quercus ilex in shrub-dominated communities within a
      Mediterranean ecosystem: do mycorrhizal partners matter?
AB  - Positive plant-plant interaction is a widespread phenomenon, especially in harsh
      environments, which can contribute to secondary successions. Here, we
      investigated whether Arbutus unedo positively influences Quercus ilex
      establishment in shrub communities by abiotic and/or biotic interactions in a
      Mediterranean forest ecosystem, where we previously showed that A. unedo and Q.
      ilex share numerous species of mycorrhizal fungi. In a first field experiment,
      patterns of Q. ilex survivorship were documented. During the summer following
      germination, a majority of seedlings survived in A. unedo chaparral (AU), whereas
      most of them died in previous succession stages dominated by Erica arborea (EA).
      These results showed that survival of the Q. ilex seedling is succession stage
      dependent, probably due to the differential effects of the summer drought. In a
      second experiment, Q. ilex seedlings were used as bait plants to investigate the
      mycorrhizal inoculum in EA and AU. Morphotyping and molecular typing revealed 2.5
      times higher colonization in AU than in EA, with more diverse fungi. Our results
      demonstrate that A. unedo facilitates mycorrhization of Q. ilex by hosting
      compatible ectomycorrhizal symbionts and positively influences seedling survival
      by buffering abiotic conditions. A comprehensive understanding of facilitation
      should thus include investigations of the soil biological patterns.

PMID- 19175679
TI  - Characterization of the alpha-haemolysin determinant from the human
      enteropathogenic Escherichia coli O26 plasmid pEO5.
AB  - The 157-kb conjugative plasmid pEO5 encoding alpha-haemolysin in strains of human
      enteropathogenic Escherichia coli (EPEC) O26 was investigated for its
      relationship with EHEC-haemolysin-encoding plasmids of enterohaemorrhagic E. coli
      (EHEC) O26 and O157 strains. Plasmid pEO5 was found to be compatible with EHEC
      virulence plasmids and did not hybridize in Southern blots with plasmid pO157
      from the EHEC O157:H7 strain EDL933, indicating that both plasmids were
      unrelated. A 9227-bp stretch of pEO5 DNA encompassing the entire alpha-hlyCABD
      operon was sequenced and compared for similarity to plasmid and chromosomally
      inherited alpha-hly determinants. The alpha-hly determinant of pEO5 (7252 bp) and
      its upstream region was most similar to corresponding sequences of the murine E.
      coli alpha-hly plasmid pHly152, in particular, the structural alpha-hlyCABD genes
      (99.2% identity) and the regulatory hlyR regions (98.8% identity). pEO5 and alpha
      hly plasmids of EPEC O26 strains from humans and cattle were very similar for the
      regions encompassing the structural alpha-hlyCABD genes. The major difference
      found between the hly regions of pHly152 and pEO5 is caused by the insertion of
      an IS2 element upstream of the hlyC gene in pHly152. The presence of transposon
      like structures at both ends of the alpha-hly sequence indicates that this pEO5
      virulence factor was probably acquired by horizontal gene transfer.

PMID- 19175680
TI  - Prevalence of urinary and faecal incontinence and nocturnal enuresis and
      attitudes to treatment and help-seeking amongst a community-based representative
      sample of adults in the United Kingdom.
AB  - AIM: To determine relative prevalence in the same population of urinary
      incontinence (UI), faecal incontinence (FI) and nocturnal enuresis (NE). To
      explore attitudes and behaviours relating to help-seeking and beliefs about
      incontinence prevalence, impact, causes and treatments. DESIGN: Online survey.
      SUBJECTS: A total of 1040 community-based adults in the UK, representative in
      terms of age, gender, region and socio-economic status. OUTCOMES: Prevalence of
      UI, FI and NE; help-seeking behaviour and beliefs; beliefs about cause, impact
      and treatment of incontinence. RESULTS: Twenty-three per cent (n = 239) reported
      UI, 11% (n = 110) FI and 6% (n = 57) NE. Of those known to have sought help, 77%
      did so from a general practitioner (GP). Of those with no incontinence, 75% said
      they would seek help from a GP, while 23% said they did not know who they would
      seek help from. Many were unsure whether treatments were available. Around 90%
      recognised the serious personal impact of incontinence. CONCLUSIONS: This survey
      suggests that, relative to UI, the prevalence of FI and NE may be higher than
      previous UK studies. That the majority of those who had sought help did so from a
      GP, and that those with no incontinence thought that they would do so if
      affected, underlines the importance of GP education in the diagnosis and
      management of incontinence and the need to raise public awareness of other
      sources of help. That many respondents were unsure of treatment options and yet
      aware of the impact of incontinence underlines the importance of awareness
      raising.

PMID- 19175681
TI  - Islet-like cell clusters occur naturally in human gall bladder and are retained
      in diabetic conditions.

PMID- 19175683
TI  - Human islet-derived precursor cells can cycle between epithelial clusters and
      mesenchymal phenotypes.
AB  - We showed previously that undifferentiated, proliferating human islet-derived
      precursor cells (hIPCs) are a type of mesenchymal stem/stromal cell (MSC) that
      can be induced by serum deprivation to form clusters and ultimately differentiate
      in vitro to endocrine cells. We also demonstrated that partially differentiated
      hIPC clusters, when implanted under the kidney capsules of mice, continued to
      differentiate in vivo into hormone-producing cells. However, we noted that not
      all hIPC preparations yielded insulin-secreting cells in vivo and that in some
      animals no hormone-expressing cells were found. This suggested that the implanted
      cells were not always irreversibly committed to further differentiation and may
      even de-differentiate to a mesenchymal phenotype. In this study, we show that
      human cells with a mesenchymal phenotype are indeed found in the grafts of mice
      implanted with hIPCs in epithelial cell clusters (ECCs), which are obtained after
      4-day in vitro culture of hIPCs in serum-free medium (SFM); mesenchymal cells
      were predominant in some grafts. We could mimic the transition of ECCs to de
      differentiated mesenchymal cells in vitro by exposure to foetal bovine serum
      (FBS) or mouse serums, and to a significantly lesser extent to human serum. In a
      complementary series of experiments, we show that mouse serum and FBS are more
      effective stimulants of mesenchymal hIPC migration than is human serum. We found
      that proliferation was not needed for the transition from ECCs to de
      differentiated cells because mitomycin-treated hIPCs that could not proliferate
      underwent a similar transition. Lastly, we show that cells exhibiting a
      mesenchymal phenotype can be found in grafts of adult human islets in mice. We
      conclude that epithelial-to-mesenchymal transition (EMT) of cells in hIPC ECCs
      can occur following implantation in mice. This potential for EMT of human islets
      or differentiated precursor cells must be considered in strategies for cell
      replacement therapy for diabetes.

PMID- 19175684
TI  - BMP-9-induced osteogenic differentiation of mesenchymal progenitors requires
      functional canonical Wnt/beta-catenin signalling.
AB  - Bone morphogenetic protein 9 (BMP-9) is a member of the transforming growth
      factor (TGF)-beta/BMP superfamily, and we have demonstrated that it is one of the
      most potent BMPs to induce osteoblast differentiation of mesenchymal stem cells
      (MSCs). Here, we sought to investigate if canonical Wnt/beta-catenin signalling
      plays an important role in BMP-9-induced osteogenic differentiation of MSCs.
      Wnt3A and BMP-9 enhanced each other's ability to induce alkaline phosphatase
      (ALP) in MSCs and mouse embryonic fibroblasts (MEFs). Wnt antagonist FrzB was
      shown to inhibit BMP-9-induced ALP activity more effectively than Dkk1, whereas a
      secreted form of LPR-5 or low-density lipoprotein receptor-related protein (LRP)
      6 exerted no inhibitory effect on BMP-9-induced ALP activity. beta-Catenin
      knockdown in MSCs and MEFs diminished BMP-9-induced ALP activity, and led to a
      decrease in BMP-9-induced osteocalcin reporter activity and BMP-9-induced
      expression of late osteogenic markers. Furthermore, beta-catenin knockdown or
      FrzB overexpression inhibited BMP-9-induced mineralization in vitro and ectopic
      bone formation in vivo, resulting in immature osteogenesis and the formation of
      chondrogenic matrix. Chromatin immunoprecipitation (ChIP) analysis indicated that
      BMP-9 induced recruitment of both Runx2 and beta-catenin to the osteocalcin
      promoter. Thus, we have demonstrated that canonical Wnt signalling, possibly
      through interactions between beta-catenin and Runx2, plays an important role in
      BMP-9-induced osteogenic differentiation of MSCs.

PMID- 19175685
TI  - Invadopodia biogenesis is regulated by caveolin-mediated modulation of membrane
      cholesterol levels.
AB  - Invadopodia are proteolytically active protrusions formed by invasive tumoural
      cells when grown on an extracellular matrix (ECM) substratum. Clearly,
      invadopodia are specialized membrane domains acting as sites of signal
      transduction and polarized delivery of components required for focalized ECM
      degradation. For these reasons, invadopodia are a model to study focal ECM
      degradation by tumour cells. We investigated the features of invadopodia membrane
      domains and how altering their composition would affect invadopodia biogenesis
      and function. This was achieved through multiple approaches including
      manipulation of the levels of cholesterol and other lipids at the plasma
      membrane, alteration of cholesterol trafficking by acting on caveolin 1
      expression and phosphorylation. We show that cholesterol depletion impairs
      invadopodia formation and persistence, and that invadopodia themselves are
      cholesterol-rich membranes. Furthermore, the inhibition of invadopodia formation
      and ECM degradation after caveolin 1 knock-down was efficiently reverted by
      simple provision of cholesterol. In addition, the inhibitory effect of caveolin
      3(DGV) expression, a mutant known to block cholesterol transport to the plasma
      membrane, was similarly reverted by provision of cholesterol. We suggest that
      invadopodia biogenesis, function and structural integrity rely on appropriate
      levels of plasma membrane cholesterol, and that invadopodia display the
      properties of cholesterol-rich membranes. Also, caveolin 1 exerts its function in
      invadopodia formation by regulating cholesterol balance at the plasma membrane.
      These findings support the connection between cholesterol, cancer and caveolin 1,
      provide further understanding of the role of cholesterol in cancer progression
      and suggest a mechanistic framework for the proposed anti-cancer activity of
      statins, tightly related to their blood cholesterol-lowering properties.

PMID- 19175686
TI  - Interstitial cells from rat middle cerebral artery belong to smooth muscle cell
      type.
AB  - It is now established that non-contractile cells with thin filopodia, also called
      vascular interstitial cells (VICs), are constitutively present in the media of
      many, if not all, blood vessels. The aim of this study was to determine the type
      of cell lineage to which arterial VICs belong using immunocytochemical, and real
      time and reverse transcription PCR (RT-PCR). Using RT-PCR, we compared gene
      expression profiles of single VICs and smooth muscle cells (SMCs) freshly
      dispersed from rat middle cerebral artery. Both VICs and SMCs expressed the SMC
      marker, smooth muscle myosin heavy chain (SM-MHC), but did not express
      fibroblast, pericyte, neuronal, mast cell, endothelial or stem cell markers.
      Freshly isolated VICs also did not express c-kit, which is the marker for
      interstitial cells of Cajal in the gastrointestinal tract. Immunocytochemical
      labelling of contractile proteins showed that VICs and SMCs expressed SM-MHC
      similarly to the same degree, but VICs in contrast to SMCs had decreased
      expression of alpha-SM-actin and very low or no expression of calponin. Real-time
      RT-PCR was consistent with immunocytochemical experiments and showed that VICs
      had four times lower gene expression of calponin comparing to SMCs, which may
      explain VICs' inability to contract. VICs had greater expression than SMCs of
      structural proteins such as non-muscular beta-actin and desmin. The results
      obtained suggest that VICs represent a subtype of SMCs and may originate from the
      same precursor as SMCs, but later develop filopodia and a non-contractile cell
      phenotype.

PMID- 19175687
TI  - Suppression of cellular immunity by cord blood-derived unrestricted somatic stem
      cells is cytokine-dependent.
AB  - Unrestricted somatic stem cells (USSC) have the potential to differentiate into
      tissues derived from all three germinal layers and therefore hold promise for use
      in regenerative therapies. Furthermore, they have haematopoietic stromal
      activity, a characteristic that may be exploited to enhance haematopoietic
      engraftment. Both applications may require USSC to be used in an allogeneic, HLA
      mismatched setting. We have therefore studied their in vitro interaction with
      cellular immunity. USSC showed no allostimulatory activity and caused only
      minimal inhibition of allogeneic T-cell responses. However, following pre
      stimulation with IFNgamma and TNFalpha, they inhibited T-cell proliferation in an
      indoleamine 2, 3-dioxygenase-dependent manner and suppressed graft-versus-host
      type reactions. In addition, USSC inhibited DC maturation and function. This
      inhibition was overridden by stronger DC maturation signals provided by IL-1beta,
      IL-6, PGE(2) and TNFalpha compared to TNFalpha alone. Pre-stimulation of USSC
      with IFNgamma and TNFalpha had a similar effect: Inhibition of DC maturation was
      no longer observed. Thus, USSC are conditionally immunosuppressive, and IFNgamma
      and TNFalpha constitute a switch, which regulates their immunological properties.
      They either suppress T-cell responses in the presence of both cytokines or in
      their absence block DC differentiation and function. These activities may
      contribute to fine-tuning the immune system especially at sites of tissue damage
      in order to ensure appropriate differentiation of USSC and subsequent tissue
      repair. Therapeutically, they may help to protect USSC and possibly their progeny
      from immune rejection.

PMID- 19175682
TI  - Targeting histone deacetylases for the treatment of disease.
AB  - The 'histone code' is a well-established hypothesis describing the idea that
      specific patterns of post-translational modifications to histones act like a
      molecular 'code' recognized and used by non-histone proteins to regulate specific
      chromatin functions. One modification, which has received significant attention,
      is that of histone acetylation. The enzymes that regulate this modification are
      described as lysine acetyltransferases or KATs, and histone deacetylases or
      HDACs. Due to their conserved catalytic domain HDACs have been actively targeted
      as a therapeutic target. The pro-inflammatory environment is increasingly being
      recognized as a critical element for both degenerative diseases and cancer. The
      present review will discuss the current knowledge surrounding the clinical
      potential and current development of histone deacetylases for the treatment of
      diseases for which a pro-inflammatory environment plays important roles, and the
      molecular mechanisms by which such inhibitors may play important functions in
      modulating the pro-inflammatory environment.

PMID- 19175688
TI  - Xanthine oxidase inhibitor allopurinol attenuates the development of diabetic
      cardiomyopathy.
AB  - In this study, we investigated the effect of the xanthine oxidase (XO) inhibitor,
      allopurinol (ALP), on cardiac dysfunction, oxidative-nitrosative stress,
      apoptosis, poly(ADP-ribose) polymerase (PARP) activity and fibrosis associated
      with diabetic cardiomyopathy in mice. Diabetes was induced in C57/BL6 mice by
      injection of streptozotocin. Control and diabetic animals were treated with ALP
      or placebo. Left ventricular systolic and diastolic functions were measured by
      pressure-volume system 10 weeks after established diabetes. Myocardial XO,
      p22(phox), p40(phox), p47(phox), gp91(phox), iNOS, eNOS mRNA and/or protein
      levels, ROS and nitrotyrosine (NT) formation, caspase3/7 and PARP activity,
      chromatin fragmentation and various markers of fibrosis (collagen-1, TGF-beta,
      CTGF, fibronectin) were measured using molecular biology and biochemistry methods
      or immunohistochemistry. Diabetes was characterized by increased myocardial,
      liver and serum XO activity (but not expression), increased myocardial ROS
      generation, p22(phox), p40(phox), p47(phox), p91(phox) mRNA expression, iNOS (but
      not eNOS) expression, NT generation, caspase 3/7 and PARP activity/expression,
      chromatin fragmentation and fibrosis (enhanced accumulation of collagen, TGF
      beta, CTGF and fibronectin), and declined systolic and diastolic myocardial
      performance. ALP attenuated the diabetes-induced increased myocardial, liver and
      serum XO activity, myocardial ROS, NT generation, iNOS expression, apoptosis,
      PARP activity and fibrosis, which were accompanied by improved systolic (measured
      by the evaluation of both load-dependent and independent indices of myocardial
      contractility) and diastolic performance of the hearts of treated diabetic
      animals. Thus, XO inhibition with ALP improves type 1 diabetes-induced cardiac
      dysfunction by decreasing oxidative/nitrosative stress and fibrosis, which may
      have important clinical implications for the treatment and prevention of diabetic
      cardiomyopathy and vascular dysfunction.

PMID- 19175689
TI  - Oncolytic virotherapy for advanced liver tumours.
AB  - Primary and metastatic neoplasms of the liver account for more than a million
      deaths per year worldwide. Despite decades of research, effective novel therapies
      for these cancers are urgently needed. Oncolytic virotherapeutics represent a
      novel class of pharmacophore that holds promise for the treatment of hepatic
      neoplasms. Cancer-specific replication is followed by oncolysis, virus spreading
      and infection of adjacent cancer cells. This process is then repeated.
      Virotherapeutics target multiple genetic pathways involved in carcino-genesis,
      and demonstrate activity against apoptosis-resistant tumour cells. This platform
      can also exploit the advantage of multiple intrinsic anti-cancer therapeutic
      mechanisms, combining direct viral oncolysis with therapeutic transgene
      expression. Recent advances in pre-clinical and clinical studies are revealing
      the potential of this unique therapeutic class, in particular for liver cancers.
      This review summarizes the available data on applying oncolytic virotherapeutics
      to hepatic neoplasms to date, and discusses the challenges and future directions
      for virotherapy.

PMID- 19175691
TI  - Ginkgo biloba extract EGb 761 exerts anti-angiogenic effects via activation of
      tyrosine phosphatases.
AB  - The standardised Ginkgo biloba extract EGb 761 (Dr. Willmar Schwabe
      Pharmaceuticals, Karlsruhe, Germany) is one of the most widely used herbal
      remedies. Indications for this extract range from dementia to peripheral vascular
      disease, based on well-documented vascular effects. Surprisingly, the actions of
      EGb 761 on angiogenesis as a function of vascular cells have not been
      investigated to date. The anti-cancer activity of EGb 761 in vitro and
      epidemiological data showing reduced risk for ovarian cancer in regular users
      have prompted us to investigate this issue. We show an anti-angiogenic profile of
      EGb 761 in vitro (inhibited proliferation, migration and tube formation of
      endothelial cells) and in vivo in the chicken chorio-allantoic membrane (CAM)
      assay. An analysis of the underlying mechanisms indicates inhibition of growth
      factor-induced extracellular signal-regulated kinase (ERK) phosphorylation by EGb
      761. Inhibitory effects of EGb 761 on ERK as well as of the upstream kinases map
      erk-kinase (MEK) and rapidly growing fibrosarcoma (Raf)-1 could be completely
      reversed by pre-treatment with sodium vanadate (inhibitor of tyrosine
      phosphatases). Sodium vanadate also reversed the EGb 761-induced inhibition of
      endothelial cell migration. Focusing on tyrosine phosphatases upstream of the Raf
      MEK-ERK cascade, we identified the tyrosine phosphatase Src homology-2 domain
      containing phosphatase 1 (SHP-1) as one target of EGb 761. SHP-1 was rapidly
      activated by EGb 761, and silencing SHP-1 (siRNA) abrogated reduction of
      endothelial proliferation by EGb 761. In summary, we identify EGb 761 as a potent
      anti-angiogenic drug. The underlying mechanism is the activation of protein
      tyrosine phosphatases, leading to inhibition of the Raf-MEK-ERK pathway. These
      findings provide a rational basis for using EGb 761 for an additional therapeutic
      indication: anti-angiogenesis-based tumour prevention and adjuvant therapy.

PMID- 19175692
TI  - Environmental enrichment alters dentate granule cell morphology in oldest-old
      rat.
AB  - The hippocampus of aged rats shows marked age-related morphological changes that
      could cause memory deficits. Experimental evidence has established that
      environmental enrichment attenuates memory deficits in aged rats. We therefore
      studied whether environmental enrichment produces morphological changes on the
      dentate granule cells of aged rats. Fifteen male Sprague-Dawley rats, 24 months
      of age, were randomly distributed in two groups that were housed under standard
      (n = 7) or enriched (n = 8) environmental conditions for 26 days. Quantitative
      data of dendritic morphology from dentate gyrus granule cells were obtained on
      Golgi-Cox stained sections. Environmental enrichment significantly increased the
      complexity and size of dendritic tree (total number of segments increased by 61%
      and length by 116%), and spine density (88% increase). There were large
      interindividual differences within the enriched group, indicating differential
      individual responses to environmental stimulation. Previous studies in young
      animals have shown changes produced by environmental enrichment in the morphology
      of dentate gyrus granule cells. The results of the present study show that
      environmental enrichment can also produce changes in dentate granule cell
      morphology in the senescent brain. In conclusion, the hippocampus retains its
      neuroplastic capacity during aging, and enriched environmental housing conditions
      can attenuate age-related dendritic regression and synaptic loss, thus preserving
      memory functions.

PMID- 19175690
TI  - Biomimetism, biomimetic matrices and the induction of bone formation.
AB  - INTRODUCTION: the induction of bone formation, the emergence of the skeleton, of
      the vertebrates and of Homo species * Different strategies for the induction of
      bone formation. Biological significance of redundancy and synergistic induction
      of bone formation. Biomimetism and biomimetic matrices self-assembling the
      induction of bone formation The concavity: the shape of life and the induction of
      bone formation. Influence of geometry on the expression of the osteogenic
      phenotype. Conclusion and therapeutic perspectives on porous biomimetic matrices
      with intrinsic osteoinductivity Bone formation by induction initiates by
      invocation of osteogenic soluble molecular signals of the transforming growth
      factor-beta (TGF-beta) superfamily; when combined with insoluble signals or
      substrata, the osteogenic soluble signals trigger the ripple-like cascade of cell
      differentiation into osteoblastic cell lines secreting bone matrix at site of
      surgical implantation. A most exciting and novel strategy to initiate bone
      formation by induction is to carve smart self-inducing geometric concavities
      assembled within biomimetic constructs. The assembly of a series of repetitive
      concavities within the biomimetic constructs is endowed with the striking
      prerogative of differentiating osteoblast-like cells attached to the biomimetic
      matrices initiating the induction of bone formation as a secondary response.
      Importantly, the induction of bone formation is initiated without the exogenous
      application of the osteogenic soluble molecular signals of the TGF-beta
      superfamily. This manuscript reviews the available data on this fascinating
      phenomenon, i.e. biomimetic matrices that arouse and set into motion the
      mammalian natural ability to heal thus constructing biomimetic matrices that in
      their own right set into motion inductive regenerative phenomena initiating the
      cascade of bone differentiation by induction biomimetizing the remodelling cycle
      of the primate cortico-cancellous bone.

PMID- 19175695
TI  - Separating the influences of environment and species interactions on patterns of
      distribution and abundance: competition between large herbivores.
AB  - 1. Much recent research has focused on the use of species distribution models to
      explore the influence(s) of environment (predominantly climate) on species'
      distributions. A weakness of this approach is that it typically does not consider
      effects of biotic interactions, including competition, on species' distributions.
      2. Here we identify and quantify the contribution of environmental factors
      relative to biotic factors (interspecific competition) to the distribution and
      abundance of three large, wide-ranging herbivores, the antilopine wallaroo
      (Macropus antilopinus), common wallaroo (Macropus robustus) and eastern grey
      kangaroo (Macropus giganteus), across an extensive zone of sympatry in tropical
      northern Australia. 3. To assess the importance of competition relative to
      habitat features, we constructed models of abundance for each species
      incorporating habitat only and habitat + the abundance of the other species, and
      compared their respective likelihoods using Akaike's information criterion. We
      further assessed the importance of variables predicting abundance across models
      for each species. 4. The best-supported models of antilopine wallaroo and eastern
      grey kangaroo abundance included both habitat and the abundance of the other
      species, providing evidence of interspecific competition. Contrastingly, models
      of common wallaroo abundance were largely influenced by climate and not the
      abundance of other species. The abundance of antilopine wallaroos was most
      influenced by water availability, eastern grey kangaroo abundance and the
      frequency of late season fires. The abundance of eastern grey kangaroos was most
      influenced by aspects of climate, antilopine wallaroo abundance and a measure of
      cattle abundance. 5. Our study demonstrates that where census and habitat data
      are available, it is possible to reveal species' interactions (and measure their
      relative strength and direction) between large, mobile and/or widely-distributed
      species for which competition is difficult to demonstrate experimentally. This
      allows discrimination of the influences of environmental factors and species
      interactions on species' distributions, and should therefore improve the
      predictive power of species distribution models.

PMID- 19175696
TI  - miRNAS in normal and diseased skeletal muscle.
AB  - The last 20 years have witnessed major advances in the understanding of muscle
      diseases and significant inroads are being made to treat muscular dystrophy.
      However, no curative therapy is currently available for any of the muscular
      dystrophies, despite the immense progress made using several approaches and only
      palliative and symptomatic treatment is available for patients. The discovery of
      miRNAs as new and important regulators of gene expression is expected to broaden
      our biological understanding of the regulatory mechanism in muscle by adding
      another dimension of regulation to the diversity and complexity of gene
      regulatory networks. As important regulators of muscle development, unravelling
      the regulatory circuits involved may be challenging, given that a single miRNA
      can regulate the expression of many mRNA targets. Although the identification of
      the regulatory targets of miRNAs in muscle is a challenge, it will be critical
      for placing them in genetic pathways and biological contexts. Therefore,
      combining informatics, biochemical and genetic approaches will not only expected
      to reveal the elucidation of the miRNA regulatory network in skeletal muscle and
      to bring a better knowledge on muscle tissue regulation but will also raise new
      opportunities for therapeutic intervention in muscular dystrophies by identifying
      candidate miRNAs as potential targets for clinical application.

PMID- 19175693
TI  - Molecular drug targets in myeloproliferative neoplasms: mutant ABL1, JAK2, MPL,
      KIT, PDGFRA, PDGFRB and FGFR1.
AB  - Therapeutically validated oncoproteins in myeloproliferative neoplasms (MPN)
      include BCR-ABL1 and rearranged PDGFR proteins. The latter are products of intra-
      (e.g. FIP1L1-PDGFRA) or inter-chromosomal (e.g. ETV6-PDGFRB) gene fusions. BCR
      ABL1 is associated with chronic myelogenous leukaemia (CML) and mutant PDGFR with
      an MPN phenotype characterized by eosinophilia and in addition, in case of FIP1L1
      PDGFRA, bone marrow mastocytosis. These genotype-phenotype associations have been
      effectively exploited in the development of highly accurate diagnostic assays and
      molecular targeted therapy. It is hoped that the same will happen in other MPN
      with specific genetic alterations: polycythemia vera (JAK2 V617F and other JAK2
      mutations), essential thrombocythemia (JAK2V617F and MPL515 mutations), primary
      myelofibrosis (JAK2 V617F and MPL515 mutations), systemic mastocytosis (KITD816V
      and other KIT mutations) and stem cell leukaemia/lymphoma (ZNF198-FGFR1 and other
      FGFR1 fusion genes). The current review discusses the above listed mutant
      molecules in the context of their value as drug targets.

PMID- 19175697
TI  - MicroRNA and cancer--focus on apoptosis.
AB  - MicroRNAs (miRs) are small non-coding RNAs regulating gene expression at the post
      transcriptional and/or translational levels. miRs play important roles in diverse
      biological processes, including development, cell differentiation, proliferation
      and apoptosis. Recent evidence has shown that miR loci frequently map to cancer
      associated genomic regions and deregulated miR expression profiles are associated
      with many cancer types, implicating miRs in crucial processes that lead to
      tumourigenesis. Here, we review the current findings about miRs and
      tumourigenesis, focusing on their involvement in the apoptosis pathway. A
      significant observation is that greater than one-quarter of all known human miRs
      were reported to be deregulated in at least one cancer type. The expression of a
      subset of miRs (e.g. miR-21 and miR-155) was found to be consistently up
      regulated, whereas another subset of miRs (e.g.miR-143 and miR-145) was
      consistently down-regulated across different cancer types suggesting their
      involvement in regulating common cellular processes whose deregulation may lead
      to tumourigenesis. Several miRs were implicated to play roles in cell
      proliferation and apoptosis. Some miRs, such as miR-29b and miR-15-16, influence
      only the apoptotic pathway, whereas others including let-7/miR-98 and miR-17-92
      may play roles in both the apoptotic and cell-proliferation pathways. In
      conclusion, although our current understanding of the functions of miRs is still
      fragmentary, taken together, this review highlights the complex and intricate
      roles that miRs play in the regulation of cellular processes. Perturbation of the
      expression of miRs may thus lead to tumourigenesis.

PMID- 19175698
TI  - Advances in microRNAs: implications for immunity and inflammatory diseases.
AB  - Since their discovery in 1993 and the introduction of the term microRNA in 2001,
      it has become evident that microRNAs (miRNAs) involved in many biological
      processes, including development, differentiation, proliferation and apoptosis.
      The function of miRNA the control of protein production in cells by sequence
      specific targeting of mRNAs for translational repression or mRNA degradati
      Interestingly, immune genes are apparently preferentially targeted by miRNAs
      compared to the average of the human genome, indicat the significance of miRNA
      mediated regulation for normal immune responses. Here, we review what is known
      about the role of miRN in the pathogenesis of immune-related diseases such as
      chronic inflammatory skin diseases, autoimmunity and viral infections.

PMID- 19175699
TI  - miR-21: a small multi-faceted RNA.
AB  - More than 1000 microRNAs (miRNAs) are expressed in human cells, some tissue or
      cell type specific, others considered as house-keeping molecules. Functions and
      direct mRNA targets for some miRNAs have been relatively well studied over the
      last years. Every miRNA potentially regulates the expression of numerous protein
      coding genes (tens to hundreds), but it has become increasingly clear that not
      all miRNAs are equally important; diverse high-throughput screenings of various
      systems have identified a limited number of key functional miRNAs over and over
      again. Particular miRNAs emerge as principal regulators that control major cell
      functions in various physiological and pathophysiological settings. Since its
      identification 3 years ago as the miRNA most commonly and strongly up-regulated
      in human brain tumour glioblastoma [1], miR-21 has attracted the attention of
      researchers in various fields, such as development, oncology, stem cell biology
      and aging, becoming one of the most studied miRNAs, along with let-7, miR-17-92
      cluster ('oncomir-1'), miR-155 and a few others. However, an miR-21 knockout
      mouse has not yet been generated, and the data about miR-21 functions in normal
      cells are still very limited. In this review, we summarise the current knowledge
      of miR-21 functions in human disease, with an emphasis on its regulation,
      oncogenic role, targets in human cancers, potential as a disease biomarker and
      novel therapeutic target in oncology.

PMID- 19175703
TI  - Liposomes in dermatology today.
AB  - Liposomes are vesicles consisting of spherical phospholipid bi-layers with
      specific properties making them useful for topical application of drugs. Liposome
      research has expanded considerably over the last 30 years and nowadays, it is
      possible to construct a wide range of liposomes varying in size, phospholipids
      composition and surface characteristics to suit the specific application for
      which they are intended. In dermatology, the topical application of liposomes has
      proven to be of therapeutic value. Liposomes can be used as carriers for
      hydrophilic as well as lipophilic therapeutic agents because of their amphipathic
      character. They may improve stabilization of instable drugs by encapsulating them
      and serve as penetration enhancers facilitating the transport of compounds that
      otherwise cannot penetrate the skin. Liposomes help in reducing skin irritation
      by sustaining the release of drugs and by hydration of the epidermis. They also
      have the potential to target drugs into the pilosebaceous structures and hence
      they have an additional advantage for treatment of hair follicle-associated
      disorders. Clinical data indicate that 5-ALA encapsulated in liposomes improves
      the quality of Fluorescence Diagnosis by ALA-induced Porphyrins (FD) and
      optimizes the results of Photodynamic Therapy (PDT).

PMID- 19175701
TI  - Myocardial interstitial Cajal-like cells (ICLC) in caveolin-1 KO mice.
AB  - Abstract We compared, by transmission electron microscopy (TEM), the
      ultrastructure of interstitial Cajal-like cells (ICLC) in normal mammalian
      myocardium versus caveolin-1 null mice. TEM showed that myocardial ICLCs of
      caveolin-1-deficient mice retain their main ultrastructural characteristics, for
      example, location among cardiomyocytes, close vicinity to nerves and/or blood
      capillaries, specialized cell-to-cell junctions, presence of 2-3 typical
      processes, which are very long (several tens of micrometres), but are very thin
      (0.1-0.2 microm) and moniliform. However, the most striking modification of
      myocardial ICLC in caveolin-1 KO mice was the absence of caveolae. Beyond this
      main observation, three other findings could be reported: (1) the absence of
      caveolae in capillary endothelium, (2) persistence of (some) caveolae at the
      level of cardiomyocte sarcolemma or vascular smooth muscle cell sarcolemma and
      (3) (un)expected ultrastructural modifications such as increased thickness of
      capillary basement membrane and increased autophagy of several cardiomyocytes.

PMID- 19175704
TI  - Dermatofibroma: a possible model of local fibrosis with epithelial/mesenchymal
      cell interaction.
AB  - Dermatofibromas are benign dermal nodules usually seen on the extremities;
      however, whether a dermatofibroma is a reactive fibrous hyperplasia or a true
      neoplasm is still unclear. Fibrous type dermatofibromas might be regarded as the
      symptom of local fibrotic processes and thus present a possible model of local
      fibrosis. Interaction between proliferated dermatofibroma fibroblasts and
      overlying elongated epidermis suggests a relationship between keratinocytes and
      mesenchymal cells. We herein describe current insights into the pathogenesis of
      dermatofibromas and explore the possible involvement of immunocytes around
      fibroblasts and effector cells which play an important role in the development of
      dermatofibromas.

PMID- 19175700
TI  - The molecular machines that mediate microRNA maturation.
AB  - MicroRNAs (miRNA) are small RNAs that regulate the translation of thousands of
      message RNAs and play a profound role in mammalian biology. Over the past 5
      years, significant advances have been made towards understanding the pathways
      that generate miRNAs and the mechanisms by which miRNAs exert their regulatory
      functions. An emerging theme is that miRNAs are both generated by and utilized by
      large and complex macromolecular assemblies. Here, we review the biology of
      mammalian miRNAs with a focus on the macromolecular complexes that generate and
      control the biogenesis of miRNAs.

PMID- 19175705
TI  - Serum and tissue expression of transforming growth factor beta 1 in  psoriasis.
AB  - BACKGROUND: In psoriasis, keratinocyte hyperplasia may be explained by imbalance
      of growth factors responsible for epidermal proliferation and altered metabolism
      of their receptors. Transforming growth factor-beta 1 (TGF-beta1) implications in
      the pathogenesis of psoriasis can be attributed to several mechanisms besides
      keratinocyte cell cycle inhibition. OBJECTIVES: To evaluate the relation between
      serum and tissue levels of TGF-beta1 in psoriasis and their correlation with
      disease parameters. PATIENTS AND METHODS: Serum and punch biopsy of involved and
      non-involved skin of 22 patients with psoriasis vulgaris and 10 controls were
      collected for quantification of TGF-beta1 by enzyme-linked immunosorbent assay
      kit. RESULTS: Serum level of TGF-beta1 in psoriatic patients was higher than
      controls in a statistically non-significant manner. Correlations between serum
      level of TGF-beta1 and extent of the disease (P = 0.007) and Psoriasis Area and
      Severity Index (PASI) score (P = 0.005) were observed. Mean tissue levels of TGF
      beta1 were highest in psoriatic lesions in contrast to normal skin of psoriatic
      patients and healthy controls, but not statistically significant. Correlation
      between tissue levels of TGF-beta1 in non-involved skin and extent of the disease
      (P = 0.007) and PASI score (P = 0.013) was detected. Correlation was detected
      between levels of TGF-beta1 in psoriatic plaques and serum of patients (P =
      0.035), but not between levels of TGF-beta1 in non-involved skin and serum.
      CONCLUSIONS: Tissue expression of TGF-beta1 in psoriasis may be affected by the
      stage of development of the lesion. The direct relation between TGF-beta1 in
      psoriatic plaques and serum imply that the mechanisms for TGF-beta1 production
      and release in both these compartments may be related.

PMID- 19175706
TI  - Detection of gamma-hydroxybutyric acid in various drink matrices via AccuTOF
      DART.
AB  - A new screening method for detecting gamma-hydroxybutyric acid (GHB) in drink
      matrices, using the IonSense, Inc. (Saugus, MA) direct analysis in real time
      (DART) ion source coupled to a JEOL exact mass time-of-flight mass spectrometer
      (AccuTOF), was validated and compared with the current screening methodology. The
      DART ion source allows for analysis of samples under ambient conditions with
      little to no sample preparation. Fifty drink specimens were spiked at levels of
      1, 2, 3, and 4 mg/mL GHB, and analyzed on the AccuTOF-DART. Positive detection of
      GHB occurred for each of the samples at each concentration level, giving 100%
      accuracy for the samples tested. Twenty-five of the 50 drink specimens were
      spiked at 1 mg/mL GHB and tested using a color test known as the GHB Color Test
      #3. Only two of these 25 specimens tested positive for the presence of GHB,
      giving only 8% accuracy. Implementation of this new methodology as a screening
      tool for GHB analysis will quickly eliminate negative specimens allowing the
      examiner to focus analysis time on those that screened positive.

PMID- 19175707
TI  - Evaluation of internal standards for the analysis of ignitable liquids in fire
      debris.
AB  - An evaluation of eight compounds for use as an internal standard in fire debris
      analysis was conducted. Tests were conducted on tetrachloroethylene,
      chlorobenzene, n-octylbenzene, 3-phenyltolune, and deuterated compounds toluene
      d8, styrene-d8, naphthalene-d8, and diphenyl-d10 to measure the extraction
      efficiency of each compound in the presence of an interfering volatile compound
      (carbon disulfide). Other tests were conducted to evaluate whether or not the
      presence of an ignitable liquid or pyrolysis/combustion products from fire debris
      would interfere with the identification of these compounds when used as an
      internal standard. The results showed that while any of the eight compounds could
      be used as an internal standard in fire debris analysis, the more volatile
      compounds (toluene-d8, tetrachloroethylene, chlorobenzene, and styrene-d8) showed
      better extraction efficiencies at room temperature than when heated to 60 degrees
      C. Each of the less volatile compounds (naphthalene-d8, diphenyl-d10, n
      octylbenzene, and 3-phenyltolune) performed well during extraction at 60 degrees
      C, while naphthalene-d8 showed better extraction efficiency in the presence of
      competing volatiles when extracted at room temperature.

PMID- 19175708
TI  - Developmental validation of the Quantifiler Duo DNA Quantification kit for
      simultaneous quantification of total human and human male DNA and detection of
      PCR inhibitors in biological samples.
AB  - The Quantifiler Duo DNA Quantification kit enables simultaneous quantification of
      human DNA and human male DNA as well as detection of inhibitors of PCR in a
      single real-time PCR well. Pooled human male genomic DNA is used to generate
      standard curves for both human (ribonuclease P RNA component H1) and human male
      (sex determining region Y) specific targets. A shift in the cycle threshold
      (C(T)) values for the internal positive control monitors the presence of PCR
      inhibitors in a sample. The assay is human specific and exhibits a high dynamic
      range from 0.023 to 50 ng/microL. In addition, the multiplex assay can detect as
      little as 25 pg/microL of human male DNA in the presence of a 1000-fold excess of
      human female DNA. The multiplex assay provides assessment of the DNA extract and
      guidance for the selection of the appropriate AmpFlSTR Amplification Kit to
      obtain interpretable short tandem repeat profiles.

PMID- 19175709
TI  - Distinguishing between damage to clothing as a result of normal wear and tear or
      as a result of deliberate damage: a sexual assault case study.
AB  - This paper focuses on bra damage, specifically damage observed in hook and eye
      fasteners that are generally located at the backstraps of bras. We describe bra
      design including the method by which hook and eye fasteners are generally
      constructed. We assess bra damage in two situations where the damage observed was
      unexpected given the case scenarios. These were: (i) the complainant of an
      alleged rape attributed damage to her bra hooks to force during a struggle and
      (ii) the complainant had earlier manipulated her bra hooks in an incident not
      related to her complaint. Steriomicroscopy and reconstruction experimentation
      were necessarily used to assess the bra damage. A systematic approach to damage
      analysis was employed by the forensic practitioners to correctly identify damage
      as being a result of mechanical manipulation and therefore as falsified. This
      paper suggests that more examples of falsified damage should be documented.

PMID- 19175710
TI  - Involvement of amphetamines in sudden and unexpected death.
AB  - In the present study, the effects of amphetamine-class drugs were examined in
      cases reported to the Victorian coroner from 2001 to 2005 to determine if death
      can occur from the use of amphetamine-class drugs alone. A total of 169 cases
      were reviewed where a forensic autopsy detected amphetamine(s) in the blood.
      Pathology, toxicology, and police reports were analyzed in all cases to ascertain
      the involvement of amphetamine-class drugs in these deaths. In Victoria,
      methamphetamine (MA) is the principal abused amphetamine-class followed by
      methylenedioxymethamphetamine (MDMA). There were six cases in which a cerebral
      hemorrhage caused death and three cases in which serotonin syndrome was
      established as being caused by the interaction of MDMA and moclobemide. There
      were 19 cases in which long-term use of amphetamines was associated with heart
      disease. There were three cases where amphetamine-class drugs alone were regarded
      as the cause of death, of which two cases exhibited high levels of MDMA and
      lesser amounts of MA and/or amphetamine. There were no cases in which significant
      natural disease was absent and death was regarded as caused by the use of MA.
      There was no correlation between blood concentration of drug and outcome.

PMID- 19175711
TI  - Clinical, histological and immunohistochemical findings in oral Kaposi's sarcoma
      in a series of Mexican AIDS patients. Comparative study.
AB  - BACKGROUND: The origin of spindle cells (SC) in oral Kaposi's sarcoma (OKS) is
      still an intriguing aspect. Thus the aim of the present study was to compare the
      clinical, histological and immunohistochemical characteristics of OKS and oral
      pyogenic granuloma (OPG), in order to contribute to the knowledge of the cells
      involved in Kaposi's sarcoma pathogenesis. METHODS: In this retrospective,
      observational and comparative study, 39 OKS and 30 OPG cases were included.
      Immunohistochemical studies were performed for vimentin, alpha SMA, desmin, C
      kit, CD34, D2-40 and LANA-1 [human herpesvirus-8(HHV-8)]. Statistical comparisons
      were done using the chi-square and Wilcoxon-Mann-Whitney rank sum tests. RESULTS:
      Fourteen (35.9%) OKS cases also affected the skin, and 83.8% involved the palate.
      All OKS and OPG were positive for vimentin and CD34. OKS samples were positive
      for alpha SMA, and 25.6% expressed C-kit. All OKS cases were positive for HHV-8,
      and the number of positive cells increased significantly from early /
      intermediate to late histological stage. D2-40 was expressed in the cellular
      component and vascular walls of all OKS cases, but it was negative in OPG. HHV-8
      expression was increased in late histological stages of OKS lesions. CONCLUSIONS:
      The expression of D2-40 marker in the vascular walls and SC supports the view of
      a lymphatic differentiation in neoplastic cells of OKS. Desmin, alpha SMA, D2-40,
      C-kit and HHV-8 were the main markers differently expressed in OKS and OPG.

PMID- 19175712
TI  - Palliative effect of lafutidine on oral burning sensation.
AB  - Lafutidine is a unique histamine H(2)-receptor antagonist (H2RA) that has a
      sensitizing effect on capsaicin-sensitive afferent neurons (CSAN). This effect
      may make lafutidine useful for the treatment of burning mouth syndrome (BMS).
      METHODS: To evaluate the efficacy and safety of lafutidine in patients with oral
      burning sensation, a randomized controlled trial was performed. Patients who had
      been receiving other H2RAs with no sensitizing effect on CSAN were randomly
      assigned to receive lafutidine 10 mg twice daily for 12 weeks, instead of the
      previous H2RAs, plus gargling with azulene sulfonate sodium (ASS) (lafutidine
      group, n = 36) or to continue to receive the previous H2RAs plus ASS gargling
      (control group, n = 35). The intensity of burning sensation was scored by means
      of a visual analog scale (VAS). RESULTS: Thirty-four patients in the lafutidine
      group and 30 in the control group completed the study. In the lafutidine group,
      the rate of improvement in the VAS score as compared with the baseline value was
      significant after 4, 8, and 12 weeks of treatment (P < 0.05). The improvement
      rate was consistently higher in the lafutidine group than in the control group;
      the differences between the groups were significant (P < 0.05) after 4, 8, and 12
      weeks of treatment. Only two mild abdominal adverse events occurred in the
      lafutidine group, but neither required the termination of treatment. CONCLUSION:
      Oral lafutidine is very safe and effective for reducing the intensity of oral
      burning sensation and may therefore be a viable option for the treatment of BMS.

PMID- 19175713
TI  - Alpha lipoic acid in burning mouth syndrome--a randomized double-blind placebo
      controlled trial.
AB  - The burning mouth syndrome (BMS) is a chronic condition characterized by oral
      burning pain in the absence of clinical abnormalities and without established
      therapy. OBJECTIVES: The purpose of this study was to evaluate the effectiveness
      of alpha lipoic acid (ALA) in the management of BMS symptoms through a randomized
      double-blind placebo-controlled trial. METHODS: Thirty-eight patients (34 women
      and four men, median age 62.9 years, range 36-78) were included and 31 completed
      the study. The patients were randomized into two cycles of treatment: one with
      alpha lipoic acid and one with placebo both administered in identical capsules.
      These cycles were separated by a washout period of 20 days. The oral symptoms and
      the treatment response were assessed using a 100-mm visual analog scale before
      and after each cycle and the global perceived effect score, using a 5-point scale
      after each treatment cycle. RESULTS: The level of reduction on burning was
      significant for both treatments (paired t-test: P < 0.05; rp = 0.011; ral <
      0.001). Considering the two cycles together, 22 patients reported at least some
      improvement after ALA use and 23 patients after placebo. CONCLUSIONS: Comparison
      of the oral assessment scores of the two cycles failed to demonstrate the
      effectiveness of ALA over placebo (t-test: P > 0.05; r = 0.75).

PMID- 19175714
TI  - Toxicity in Doberman Pinchers with ventricular arrhythmias treated with
      amiodarone (1996-2005).
AB  - BACKGROUND: Asymptomatic Doberman Pinschers with dilated cardiomyopathy (DCM)
      often die suddenly owing to ventricular tachycardia that degenerates into
      ventricular fibrillation. A safe and effective antiarrhythmic drug treatment is
      needed. This will require a large, well-controlled, prospective study.
      HYPOTHESIS: Amiodarone toxicity is common in Dobermans with occult DCM and
      ventricular tachyarrhythmias refractory to antiarrhythmia therapy. Infrequent
      monitoring of hepatic function is inadequate. Frequent monitoring may be useful
      to determine dogs in which the dosage should be decreased or the drug withdrawn.
      METHODS: Medical records from the University of Georgia and Cornell University
      were searched for Doberman Pinschers diagnosed with preclinical DCM that received
      amiodarone for severe ventricular arrhythmias refractory to other antiarrhythmic
      agents. Echocardiographic data, Holter recording data, hepatic enzyme serum
      activity, and serum amiodarone concentrations were recorded. The presence of
      clinical signs of toxicity was recorded. Serum amiodarone concentrations were
      obtained in some dogs. RESULTS: Reversible toxicity was identified in 10 of 22
      (45%) dogs. CONCLUSION AND CLINICAL IMPORTANCE: Adverse effects from amiodarone
      were common and were, in part, dosage related. Patients should be monitored for
      signs of toxicity and liver enzyme activity should be measured at least monthly.

PMID- 19175715
TI  - Fluorescence in situ hybridization confirms clearance of visible Helicobacter
      spp. associated with gastritis in dogs and cats.
AB  - BACKGROUND: The results of studies examining the role of Helicobacter spp. in the
      pathogenesis of canine and feline gastritis are inconclusive. Furthermore, data
      evaluating the effectiveness of medical therapy for eradication of Helicobacter
      infection are limited. AIM: To detect Helicobacter spp. in mucosal biopsies of
      dogs and cats diagnosed with gastritis, with fluorescence in situ hybridization
      (FISH). ANIMALS: Three dogs and 2 cats with signs of chronic gastrointestinal
      disease. METHODS: Dogs and cats infected with Helicobacter spp. were treated with
      triple antimicrobial therapy and fed an elimination diet for 21 days.
      Helicobacter spp. status in endoscopic (3 dogs, 1 cat) or surgical biopsies (1
      cat) of gastric mucosa was compared pre- and posttreatment in each animal by
      histology, FISH analysis, and polymerase chain reaction (PCR). RESULTS: Gastritis
      of varying severity with intraglandular spiral bacteria was observed in all
      animals. Pretreatment diagnostic tests confirmed the presence of mucosal
      Helicobacter spp. in all animals by FISH and histopathology and in 4/5 animals by
      PCR. Rapid resolution of vomiting episodes was observed in all animals. Gastric
      biopsies performed after triple therapy revealed clearance of visible
      Helicobacter spp. by histopathology and negative FISH analysis, as well as PCR in
      all animals. CONCLUSIONS AND CLINICAL IMPORTANCE: Application of FISH to routine
      biopsy specimens enabled rapid and specific identification of Helicobacter spp.
      within the gastric mucosa of dogs and cats. Although medical therapy was useful
      in resolution of clinical signs and clearance of visible Helicobacter spp. in
      gastric biopsies, gastric inflammation persisted.

PMID- 19175716
TI  - Adverse effects of concurrent carboplatin chemotherapy and radiation therapy in
      dogs.
AB  - BACKGROUND: Concurrent chemo- and radiotherapy improves outcome of certain human
      neoplasms but with increased signs of toxicity. Reports on adverse effects of
      concurrent chemo- and radiotherapy in the veterinary literature are scant.
      OBJECTIVE: To report adverse hematologic and gastrointestinal effects of combined
      carboplatin and radiation therapy in dogs. ANIMALS: Client-owned dogs with
      spontaneously occurring neoplasia. METHODS: Retrospective case study. Medical
      records of 65 dogs were reviewed. Criteria for inclusion were administration of
      radiation according to 1 of 3 fractionation schemes (19 x 3, 16 x 3, or 12 x 4
      Gy) and administration of at least 1 concurrent carboplatin treatment at a dosage
      of 200-300 mg/m(2). Dog and treatment-related variables were analyzed for
      association with signs of intoxication. RESULTS: Median carboplatin dosage was
      200 mg/m(2) (range, 200-250 mg/m(2)). Twelve of 58 dogs (21%) developed grade 3
      or 4 neutropenia. Eleven of 56 dogs (20%) developed grade 3 or 4
      thrombocytopenia. Six of 62 dogs (10%) developed grade 3, 4, or 5
      gastrointestinal toxicosis. Analysis of association of dog and treatment-related
      variables with signs of intoxication was hampered by the small numbers of dogs in
      individual groups, and no statistically significant associations were found.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Combined modality therapy resulted in
      myelosuppression and gastrointestinal toxicosis. Future studies are needed to
      determine whether the potential benefit of combined modality therapy outweighs
      the risk of decreasing chemotherapy and radiation treatment intensity.

PMID- 19175717
TI  - Dual chamber pacemaker implantation in dogs with atrioventricular block.
AB  - BACKGROUND: Pacemaker implantation is the treatment of choice for symptomatic
      bradyarrhythmias. In dogs, a single chamber system is commonly used. In human
      patients with high-grade 2nd- or 3rd-degree atrioventricular (AV) block,
      physiologic pacing is recommended, because it improves cardiac output, blood
      pressure, exercise tolerance, and quality of life. In dogs, this type of pacing
      is seldom used. HYPOTHESIS: The implantation of a dual chamber pacemaker in dogs
      with AV block is a feasible procedure for restoring AV synchrony. ANIMALS: Thirty
      three privately owned dogs with high-grade 2nd- or 3rd-degree AV block were
      included. METHODS: Patient data of all dogs with AV block presented for pacemaker
      implantation between December 1997 and November 2004 were reviewed. RESULTS: Dual
      chamber pacemaker implantation with AV synchronous stimulation was successfully
      performed in 33/33 dogs (100%). In 9/33 (27%) major and in 12/33 (36%) minor
      complications were observed. Mean survival time for the patients discharged from
      hospital (n = 32) was 33.6 +/- 20.4 months (range, 3.9-83.5 months). CONCLUSION
      AND CLINICAL IMPORTANCE: Dual chamber pacing is a feasible procedure in dogs with
      2nd- or 3rd-degree AV block and is not associated with a higher complication rate
      compared with single chamber pacemaker systems. A major advantage over
      ventricular demand pacemaker systems is the restoration of AV synchrony for a
      substantial period of time.

PMID- 19175718
TI  - Gingival hyperplasia associated with the administration of amlodipine to dogs
      with degenerative valvular disease (2004-2008).
AB  - BACKGROUND: Calcium channel blocking drugs, usually nifedipine and less often
      amlodipine, have been reported to cause gingival hyperplasia (GH) in humans.
      HYPOTHESIS: Amlodipine, a dihydropyridine calcium channel blocking drug, can
      cause GH when administered chronically to older small dogs with degenerative
      valvular disease. ANIMALS STUDIED: From January 2004 to May 2008, 82 client-owned
      dogs with degenerative valvular disease and left atrial dilatation were treated
      with amlodipine in combination with spironolactone and enalapril and followed for
      >6 months. METHODS: Retrospective study. A chronological observation of GH in 2
      dogs treated with amlodipine in 2004 and 2006 prompted the study. Patient
      histories and medical records of each dog treated with amlodipine for
      degenerative valvular disease from January 2004 to May 2008 were reviewed.
      RESULTS: GH was observed by clients and the authors in 7 of 82 (8.5%) dogs.
      Histologic confirmation of the diagnosis was made in 2 dogs. The minimum duration
      of treatment before diagnosis of GH was 5 months. GH began to resolve within 2
      weeks of discontinuing amlodipine and resolution was complete within 6 months.
      Amlodipine administration was reinstituted in 1 dog in which GH had resolved, and
      GH reoccurred within 4 months. CONCLUSION AND CLINICAL IMPORTANCE: Long-term
      administration of amlodipine to dogs with degenerative valvular disease may cause
      GH in a small percentage of patients. GH resolves quickly after withdrawal of
      amlodipine treatment.

PMID- 19175719
TI  - Clinical evaluation of a novel liquid formulation of L-thyroxine for once daily
      treatment of dogs with hypothyroidism.
AB  - BACKGROUND: A liquid solution of levothyroxine (L-T4) is available for treatment
      of canine hypothyroidism. HYPOTHESIS: Once daily oral administration of a liquid
      L-T4 solution is effective and safe for controlling hypothyroidism in dogs.
      ANIMALS: Thirty-five dogs with naturally occurring hypothyroidism. METHODS: Dogs
      received L-T4 solution PO once daily at a starting dosage of 20 microg/kg body
      weight (BW). The dose was adjusted every 4 weeks, based on clinical signs and
      peak serum total T4 (tT4) concentrations. Target peak serum tT4 and thyroid
      stimulating hormone (TSH) concentrations, 4-6 hours posttreatment, were 35-95
      nmol/L and < 0.68 ng/mL, respectively. Dogs were followed for up to 22 weeks
      after establishment of the maintenance dose. RESULTS: Clinical signs of
      hypothyroidism improved or resolved in 91% of dogs after 4 weeks of L-T4
      treatment at 20 microg/kg once daily. The maintenance dose was established in 76,
      94, and 100% of dogs after 4, 8, and 12 weeks of treatment, respectively. This
      was 20 microg L-T4/kg BW for 79% of the dogs, 30 microg/kg BW for 15%, and 10-15
      microg/kg BW in the remaining 6%, once daily. Thereafter, median peak tT4 and TSH
      concentrations were 51 nmol/L and 0.18 ng/mL, respectively, and remained stable
      during the 22-week follow-up; clinical signs did not recur. CONCLUSIONS AND
      CLINICAL IMPORTANCE: All of the hypothyroid dogs had rapid clinical and hormonal
      responses to supplementation with the PO-administered L-T4 solution. The starting
      dosage of 20 microg L-T4/kg BW once daily was suitable for 79% of dogs.

PMID- 19175720
TI  - An investigation of the action of Neutral Protamine Hagedorn human analogue
      insulin in dogs with naturally occurring diabetes mellitus.
AB  - BACKGROUND: Neutral Protamine Hagedorn human analogue insulin (Humulin N) is
      commonly used for treatment of canine diabetes mellitus (DM). However, blood
      glucose and serum insulin concentrations in Humulin N-treated dogs with naturally
      occurring DM have not been reported. OBJECTIVE: To investigate blood glucose and
      serum insulin concentrations in the clinical setting of client-owned Humulin N
      treated dogs with naturally occurring, well-regulated DM. ANIMALS: Ten client
      owned dogs with naturally occurring, well-regulated DM. METHODS: In this clinical
      study, blood glucose and serum insulin concentrations were measured when dogs
      received food and insulin (T(0)), at approximately every half hour for the next 2
      hours, and then approximately every 2 hours for an additional 8 hours. Insulin
      duration of action was defined as the number of hours from T(0) to the lowest
      blood glucose concentration and until blood glucose concentration returned to an
      interpolated value of 70% of basal blood glucose concentration (Glucose(b)).
      RESULTS: Mean percent of insulin-induced blood glucose suppression was 49.9 +/-
      17.1% (median, 46%; range, 29-78%). Insulin duration of action ranged from 4 to
      10 hours. Blood glucose concentration increased initially and returned to
      Glucose(b) within 0.6-2.2 hours after T(0) in 5 dogs. This initial blood glucose
      surge then was followed by blood glucose suppression in all 5 dogs. CONCLUSIONS
      AND CLINICAL IMPORTANCE: These results suggest that Humulin N administered SC
      twice daily is an effective mode of treatment for dogs with naturally occurring
      DM. Postprandial hyperglycemia is present in some well-regulated diabetic dogs
      treated with Humulin N.

PMID- 19175721
TI  - Effects of firocoxib and tepoxalin on healing in a canine gastric mucosal injury
      model.
AB  - BACKGROUND: Little is known about the effect of dual cyclooxygenase (COX) and
      lipoxygenase inhibition on canine gastric mucosal healing. OBJECTIVE: This study
      compares the effects of putative dual COX and 5-lipoxygenase inhibition with that
      of COX-2 selective inhibition on gastric mucosal lesion healing in dogs. ANIMALS:
      Six normal adult mixed-breed research dogs. METHODS: Gastric body and pyloric
      lesions were induced by endoscopic biopsy. Dogs were treated with tepoxalin,
      firocoxib, or placebo for 7 days in a randomized 3-way crossover study design.
      Healing was evaluated on days 2, 4, and 7 of treatment by endoscopic lesion
      scoring. Eicosanoid concentrations in plasma and at the lesion margins were
      determined on days 2, 4, and 7. Repeated measures analyses were performed. All
      hypothesis tests were 2-sided with P < .05. Multiple comparisons were adjusted
      using Tukey's test. RESULTS: Significant treatment differences were noted in the
      pyloric lesion area measurements. Overall, the firocoxib group had larger lesions
      than the placebo (P= .0469) or tepoxalin (P= .0089) groups. Despite larger
      pyloric lesions in the firocoxib group, mucosal prostaglandin production did not
      differ significantly from placebo. In contrast, the tepoxalin group had
      significantly lower pyloric mucosal prostaglandin production compared with the
      firocoxib (P < .0001) or the placebo (P < .0001) groups but pyloric lesions were
      not significantly larger than those of the placebo group (P= .7829). CONCLUSION:
      COX-2 inhibition by firocoxib slowed wound healing by a mechanism independent of
      prostaglandin synthesis. Suppression of mucosal prostaglandin production by
      tepoxalin did not alter mucosal lesion healing compared with placebo.

PMID- 19175722
TI  - Ascites is a negative prognostic indicator in chronic hepatitis in dogs.
AB  - BACKGROUND: Chronic hepatitis (CH) in dogs is common but little is known about
      factors associated with survival. Ascites is a well-recognized negative
      prognostic indicator in humans. HYPOTHESIS: Ascites is a negative prognostic
      indicator in CH in dogs. ANIMALS: Thirty-four dogs with histologically confirmed
      CH presented to 1 institution between 1996 and 2005. METHODS: Retrospective
      observational study. CH was diagnosed by histopathology of liver tissue according
      to the WSAVA criteria. Ascites was diagnosed by abdominal ultrasound. The
      association of ascites with survival from diagnosis or onset of owner-reported
      clinical signs until death from any cause or from liver disease was analyzed.
      Ascitic and nonascitic groups were further analyzed for differences in treatment
      and sex. RESULTS: Fourteen of 34 dogs had ascites. Survival from diagnosis to
      death from liver disease was 0.4 months (95% confidence interval [CI], 0.2-0.6)
      for ascitic dogs and 24.3 months (CI 11.4-37.1) for nonascitic dogs (P < .001),
      and from onset of signs to death from liver disease was 2.0 months (CI 0.0-5.6)
      for ascitic dogs and 33.0 months (CI 8.6-57.4) for nonascitic dogs (P= .0020).
      Diet and spironolactone use differed between groups. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Ascites is a significant negative prognostic indicator in dogs with
      CH. Veterinarians and owners can use this information to aid clinical decision
      making in affected dogs.

PMID- 19175723
TI  - Juvenile pancreatic atrophy in Greyhounds: 12 cases (1995-2000).
AB  - BACKGROUND: This study describes compound failure of the endocrine and exocrine
      pancreas in Greyhounds, a condition that has not been reported in the veterinary
      literature. OBJECTIVE: To describe the clinical and pathologic findings in 12
      Greyhounds with juvenile pancreatic atrophy. ANIMALS: Ten Greyhounds presented
      for necropsy examination and 2 sibling Greyhounds presented for clinical
      evaluation before necropsy, all with a history of small-bowel diarrhea.
      PROCEDURES: Retrospective study of laboratory and pathologic findings in 12
      Greyhounds, including serum trypsin-like immunoreactivity assays, oral glucose
      tolerance testing, and serum anti-insulin antibody concentrations. RESULTS: Gross
      pancreatic atrophy was found in all 12 dogs. Histopathologic lesions were found
      in both the endocrine and exocrine pancreas and included acinar cell apoptosis,
      zymogen granule loss, cytoplasmic clearing or vacuolar change, lobular atrophy,
      islet loss, and lymphocytic or lymphoplasmacytic pancreatitis. Antemortem test
      results on the 2 Greyhound puppies indicated concurrent exocrine pancreatic
      insufficiency (EPI) and insulin-dependent diabetes mellitus (IDDM). CONCLUSIONS
      AND CLINICAL IMPORTANCE: Compound failure of the exocrine and endocrine pancreas
      is rarely reported in dogs and neither disease is well recognized in the
      Greyhound. This condition is of potential economic importance to the Greyhound
      racing industry.

PMID- 19175724
TI  - Primary hepatitis in dogs: a retrospective review (2002-2006).
AB  - BACKGROUND: Little is known about etiology, disease progression, treatment
      outcome, survival time, and factors affecting prognosis in dogs with primary
      hepatitis (PH). OBJECTIVES: To review retrospectively different forms of
      hepatitis in a referral population, by the World Small Animal Veterinary
      Association Standardization criteria. ANIMALS: One-hundred and one dogs examined
      for histologically confirmed PH between 2002 and 2006. Dogs with nonspecific
      reactive hepatitis were excluded. METHODS: Retrospective study. Medical records
      were reviewed for prevalence, signalment, clinical and clinicopathologic
      manifestation, outcome, survival time, and prognostic factors for shortened
      survival. RESULTS: PH occurred in 0.5% of dogs in this referral population. Acute
      (AH) and chronic hepatitis (CH) were diagnosed in 21 and 67 dogs, respectively.
      Progression from AH to CH occurred in 5/12 of the repeatedly sampled dogs. CH was
      idiopathic in 43 (64%) dogs, and was associated with copper accumulation in 24
      (36%) dogs. Median survival time was longer in dogs with AH than in dogs with CH
      (either idiopathic or copper associated), and dogs with lobular dissecting
      hepatitis had the shortest survival time. Prognostic factors predicting shortened
      survival were associated with decompensated liver function and cirrhosis at
      initial examination. CONCLUSIONS AND CLINICAL IMPORTANCE: The majority of PH in
      dogs is CH. Previous studies appear to have underestimated the etiologic role of
      copper in both AH and CH. Prognosis is reduced in dogs with hepatic cirrhosis or
      cirrhosis-related clinical findings. Further research into etiology and treatment
      effectiveness in all PH forms is needed.

PMID- 19175725
TI  - Use of auscultation and Doppler echocardiography in Boxer puppies to predict
      development of subaortic or pulmonary stenosis.
AB  - BACKGROUND: Boxers are predisposed to subaortic and pulmonic stenosis (SAS, PS).
      Screening of puppies may be useful in estimating the risk of their developing a
      defect that potentially compromises life expectancy or exercise tolerance.
      HYPOTHESIS: Presence of SAS or PS in adult Boxers can be predicted by
      auscultation and Doppler echocardiography at 9-10 weeks of age. ANIMALS: Eighty
      five Boxer puppies examined at 9-10 weeks of age and at 12 months of age.
      METHODS: Prospective, longitudinal observational study. Auscultation by
      stethoscope and continuous wave-Doppler echocardiography for peak velocities
      (V(max)) in the aorta (Ao) and pulmonary artery (PA). RESULTS: Intensity of heart
      murmurs in puppies correlated with V(max)Ao and V(max)PA in adults. V(max)Ao and
      V(max)PA in puppies correlated with V(max)Ao and V(max)PA in adults,
      respectively. From puppy to adult, V(max)Ao increased and V(max)PA remained
      unchanged. The negative predictive value for absent or only a soft (< or =II/VI)
      murmur in puppies being associated with V(max)Ao and PA < or = 2.4 m/s as an
      adult was 90% and < or =3.5 m/s 100%. The negative predictive value of a V(max)<
      or = 2.4 m/s as a puppy still being < or =2.4 m/s as an adult was 94% for Ao and
      96% for PA, and of a V(max)< or = 3.5 m/s, 99% for Ao and 100% for PA.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Even though V(max)Ao increases during growth
      in Boxer puppies, indicating relative narrowing of the aorta, puppies with
      V(max)Ao < or = 2.4 m/s do not usually progress to clinically have relevant SAS
      at 12 months of age.

PMID- 19175726
TI  - Serum cardiac troponin I concentration in retired racing greyhounds.
AB  - BACKGROUND: Cardiac troponin I (cTnI) is a polypeptide found specifically in
      cardiac muscle tissue that has been used as a diagnostic and prognostic indicator
      of cardiomyopathy. Increases in cTnI are associated with myocardial pathologic
      processes. However, high serum cTnI concentrations have been observed in normal
      Greyhounds. HYPOTHESIS: We hypothesized that Greyhounds have cTnI concentrations
      higher than non-Greyhound dogs, and that a separate reference range should be
      established for Greyhounds. ANIMALS: Blood samples were collected from the
      jugular vein from a group of 20 healthy Greyhound blood donors. METHODS: Analysis
      of serum cTnI was performed with an immunoassay system with a detection level of
      0.01 ng/mL, as described previously. The Greyhound values were compared with 2
      groups of Boxers with and without arrhythmogenic right ventricular cardiomyopathy
      (ARVC), and to a group of non-Boxer control dogs from a previous study. RESULTS:
      The mean cTnI concentration in Greyhounds was significantly higher (P < .0001)
      than that in non-Greyhound control dogs, although not significantly different
      from normal Boxers (P= .50), or Boxers with ARVC (P= .58). Greyhound serum cTnI
      concentrations were in the range found in Boxers with ARVC. The proposed
      reference range for cTnI in Greyhounds is 0.05-0.16 ng/mL. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Greyhounds have a reference range for serum cTnI
      concentrations that differs from that of other previously published reference
      ranges for dogs of other breeds. Until a broader database and more precise
      reference range can be established, caution should be exercised in interpreting
      serum cTnI concentrations in Greyhounds with suspected cardiac disease.

PMID- 19175727
TI  - Prospective echocardiographic and tissue Doppler imaging screening of a
      population of Maine Coon cats tested for the A31P mutation in the myosin-binding
      protein C gene: a specific analysis of the heterozygous status.
AB  - BACKGROUND: A mutation in the sarcomeric gene coding for the myosin-binding
      protein C gene has been identified in a colony of Maine Coon cats with
      hypertrophic cardiomyopathy (MyBPC3-A31P mutation). However, the close
      correlation between genotype and phenotype (left ventricular hypertrophy [LVH]
      and dysfunction) has never been assessed in a large population, particularly in
      heterozygous (Hetero) cats. OBJECTIVES: To investigate LV morphology and function
      with echocardiography and tissue Doppler imaging (TDI) in a population of Maine
      Coon cats tested for the MyBPC3-A31P mutation with focus on Hetero animals.
      ANIMALS: Ninety-six Maine Coon cats. METHODS: Prospective observational study.
      Cats were screened for the MyBPC3-A31P mutation and examined with both
      echocardiography and 2-dimensional color TDI. RESULTS: Fifty-two out of 96 cats
      did not have the mutation (wild-type genotype, Homo WT), 38/96 and 6/96 were
      Hetero- and homozygous-mutated (Homo M) cats, respectively. Only 11% of Hetero
      cats (4/38) had LVH and 29% (10/34) of Hetero cats without LVH were >4 years old
      (4.1-11.5 years). LVH was also detected in 2 Homo WT cats (4%). A significantly
      decreased (P < .05) longitudinal E/A (ratio between early and late diastolic
      myocardial velocities) in the basal segment of the interventricular septum was
      observed in Hetero cats without LVH (n = 34) compared with Homo WT cats without
      LVH (n = 50), thus confirming that the Hetero status is associated with regional
      diastolic dysfunction (P < .05). CONCLUSIONS: The heterozygous status is not
      consistently associated with LVH and major myocardial dysfunction. Moreover, Homo
      WT cats can also develop LVH, suggesting that other genetic causes might be
      implicated.

PMID- 19175728
TI  - Adenohypophyseal function in dogs with primary hypothyroidism and nonthyroidal
      illness.
AB  - BACKGROUND: A recent study of dogs with induced primary hypothyroidism (PH)
      demonstrated that thyroid hormone deficiency leads to loss of thyrotropin (TSH)
      hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement
      with large vacuolated "thyroid deficiency" cells that double-stained for growth
      hormone (GH) and TSH, indicative of transdifferentiation of somatotropes to
      thyrosomatropes. HYPOTHESIS: Similar functional changes in adenohypophyseal
      function occur in dogs with spontaneous PH as do in dogs with induced PH, but not
      in dogs with nonthyroidal illness (NTI). ANIMALS: Fourteen dogs with spontaneous
      PH and 13 dogs with NTI. METHODS: Adenohypophyseal function was investigated by
      combined intravenous administration of 4 hypophysiotropic releasing hormones (4RH
      test), followed by measurement of plasma concentrations of ACTH, GH, luteinizing
      hormone (LH), prolactin (PRL), and TSH. In the PH dogs this test was repeated
      after 4 and 12 weeks of thyroxine treatment. RESULTS: In 6 PH dogs, the basal TSH
      concentration was within the reference range. In the PH dogs, the TSH
      concentrations did not increase with the 4RH test. However, TSH concentrations
      increased significantly in the NTI dogs. Basal and stimulated GH and PRL
      concentrations indicated reversible hypersomatotropism and hyperprolactinemia in
      the PH dogs, but not in the NTI dogs. Basal and stimulated LH and ACTH
      concentrations did not differ between groups. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Dogs with spontaneous PH hypersecrete GH but have little or no TSH
      hypersecretion. Development of hyperprolactinemia (and possible galactorrhea) in
      dogs with PH seems to occur only in sexually intact bitches. In this group of
      dogs with NTI, basal and stimulated plasma adenohypophyseal hormone
      concentrations were not altered.

PMID- 19175729
TI  - Endoscopic-assisted intracranial tumor removal in dogs and cats: long-term
      outcome of 39 cases.
AB  - BACKGROUND: The benefits of endoscopic assistance to remove intracranial tumors
      in small animals are not described. OBJECTIVE: To evaluate the effectiveness of
      endoscopic-assisted intracranial tumor removal in dogs and cats. ANIMALS: Thirty
      three dogs and 6 cats with intracranial tumors. METHODS: Retrospective study.
      CBC, serum chemistry profile, coagulation testing, blood typing, and systemic
      tumor staging, which included 3-view thoracic radiographs and abdominal
      ultrasound examination, were performed to detect other significant underlying
      disease in preparation of the animal for surgery. Magnetic resonance imaging was
      used in 37/39 cases to image the brain tumor. Surgical approach was dictated by
      the location of the tumor. Histopathologic examination of the tumor tissue was
      performed in all cases. Animals were followed throughout their postoperative
      course for complications and survival times. Statistical analysis (Kaplan-Meier
      curves) was performed to obtain median survival times in dogs with meningiomas.
      RESULTS: Use of an endoscope resulted in visualization of residual tumor and
      potentially more complete removal of the brain tumors. There were no clinically
      important complications associated with the use of the endoscope. Median survival
      time was 2,104 days for dogs with forebrain meningiomas surgically removed with
      endoscopic assistance and 702 days for dogs with caudal brain meningiomas.
      CONCLUSIONS AND CLINICAL IMPORTANCE: These results demonstrate that the use of an
      endoscope to assist in brain tumor removal is apparently safe and might result in
      improved survival times.

PMID- 19175730
TI  - Evaluation of adjuvant doxorubicin-based chemotherapy for the treatment of feline
      mammary carcinoma.
AB  - BACKGROUND: Feline mammary carcinomas (FMC) are locally invasive and highly
      metastatic tumors. Because of the high metastatic potential, patients often are
      treated with adjuvant doxorubicin-based chemotherapy, but little data exist to
      evaluate the effect of this strategy. HYPOTHESIS: Adjuvant doxorubicin-based
      chemotherapy improves outcome for FMC compared with surgery alone. ANIMALS: Cats
      with naturally occurring, biopsy-confirmed FMC treated with either surgery alone
      (Sx) or with surgery plus adjuvant doxorubicin-based chemotherapy (Sx + Chemo).
      METHODS: Retrospective cohort study. Clinical data were collected and compared to
      identify differences between groups. Outcome results were determined and
      compared. Prognostic factors for disease-free survival (DFS) and overall survival
      were evaluated. RESULTS: Seventy-three cats were evaluated, of which 37 were in
      the Sx group and 36 in the Sx + Chemo group. No differences in clinical data were
      found between Sx and Sx + Chemo groups. Median DFS times for the Sx and Sx +
      Chemo groups were 372 and 676 days, respectively (P= .15) and median survival
      times (ST) were 1,406 and 848 days, respectively (P= .78). For cats that
      underwent a unilateral radical mastectomy, ST was significantly longer for the Sx
      + Chemo compared with the Sx group (1,998 versus 414 days, respectively; P= .03).
      CONCLUSIONS AND CLINICAL IMPORTANCE: This study did not find a benefit to
      adjuvant doxorubicin-based chemotherapy in cats with FMC. Additional studies are
      required to determine whether patient subgroups with negative prognostic factors
      may benefit from adjuvant chemotherapy.

PMID- 19175731
TI  - Combined gemcitabine and carboplatin therapy for carcinomas in dogs.
AB  - BACKGROUND: Response and adverse reactions to combined gemcitabine (GEM) and
      carboplatin (CARBO) therapy in dogs with carcinomas are not documented.
      HYPOTHESIS: GEM and CARBO are safe for the treatment of dogs with carcinomas.
      ANIMALS: Thirty-seven dogs with histologically or cytologically confirmed
      carcinomas. METHODS: Prospective clinical trial. Dogs were treated with GEM (2
      mg/kg, 20-30-minute infusion IV) on Days 1 and 8 and 4 hours later, CARBO (10
      mg/kg IV) on Day 1. The cycle was repeated on Day 22. RESULTS: Thirty-seven dogs
      (29 with measurable tumor) received a median of 2 cycles (range 0.5-6) for a
      total of 101 cycles administered. Twelve dogs (32%) developed neutropenia (3
      Grade 3, and 5 Grade 4) and 9 (24%) thrombocytopenia (2 Grade 3, and 1 Grade 4).
      Dogs >20 kg were twice as likely to develop thrombocytopenia (P= .023). Twenty
      seven dogs (73%) had evidence of gastrointestinal (GI) toxicosis, but most signs
      were of mild to moderate severity and self-limiting. One dog died of treatment
      related complications. Overall tumor response rate was 13%. One dog with
      metastatic prostatic carcinoma achieved a complete remission and 1 dog with
      intestinal adenocarcinoma and 1 with tonsillar squamous cell carcinoma achieved
      partial remission. Twelve dogs achieved stable disease for a median of 72 days.
      CONCLUSION AND CLINICAL IMPORTANCE: GEM and CARBO combination causes mild to
      moderate hematologic and GI toxicosis in dogs with carcinoma. Response rate in
      this study was modest, and optimization of dosing of this combination is
      required.

PMID- 19175732
TI  - Cryopreservation of canine platelets.
AB  - BACKGROUND: Platelet cryopreservation allows long-term storage and immediate
      availability of transfusion products. HYPOTHESIS: The addition of a preparation
      inhibiting platelet activation (Thrombosol, in 2% dimethyl sulfoxide [DMSO]) will
      enhance in vitro function and prolong in vivo survival of cryopreserved platelets
      compared with those preserved in 6% DMSO. ANIMALS: Thirty-three research dogs.
      METHODS: Prospective study. Eleven fresh canine apheresis platelet concentrates
      (PCs) were each split into 3 units: fresh and cryopreserved in 6% DMSO or
      Thrombosol. Platelet analysis, performed 1-10 weeks postfreezing, included in
      vitro functional testing and in vivo survival assessed by administration of
      biotinylated platelets. RESULTS: Platelet aggregation was diminished in
      cryopreserved PC. Cryopreserved platelets could be activated, as based on mean
      thrombin-stimulated P-selectin expression (6% DMSO, 23.0%; Thrombosol, 18.4%),
      although to a lesser extent than fresh PC (49.1%) (P < .0001). The mean maximum
      in vivo platelet recovery for fresh PC was 80.3%, significantly greater than
      recovery for 6% DMSO (49.2%) and Thrombosol PC (43.7%) (P< or = .001). The half
      life (days) of fresh PC (3.8 +/- 0.4) was significantly (P < .002) greater than
      that of 6% DMSO (1.9 +/- 1.0) and Thrombosol (2.4 +/- 1.1) PC, with no difference
      (P= .3) between cryopreserved PC. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Cryopreservation of canine platelets using Thrombosol did not provide any
      advantage over preservation using 6% DMSO. Cryopreserved platelets can be
      activated in vitro and provide therapeutic benefit when fresh platelets are
      unavailable. Further studies are needed to assess their in vivo hemostatic
      function.

PMID- 19175733
TI  - Ki-67 and vascular endothelial growth factor expression in intracranial
      meningiomas in dogs.
AB  - BACKGROUND: Tumor proliferation in human intracranial meningiomas can be defined
      by the reactivity of the monoclonal antibody MIB-1 to the Ki-67 antigen. Vascular
      endothelial growth factor (VEGF), a pro-angiogenic factor, is a predictive marker
      for survival of dogs with intracranial meningiomas. HYPOTHESIS: Ki-67 is
      expressed in canine intracranial meningiomas and is associated with VEGF
      expression. Ki-67 expression is a prognostic marker for patient outcome. ANIMALS:
      Seventy client-owned dogs with WHO grade I intracranial meningiomas. METHODS:
      Retrospective study assessing the degree of immunostaining for Ki-67 by MIB-1 and
      VEGF expression in intracranial meningioma tissue from dogs. MIB-1 Labeling Index
      (LI) was calculated with Image J NIH-software. Extent, intensity, and
      distribution of VEGF-expression was assessed semiquantitatively. Cross
      tabulations with Fisher's exact tests and nonparametric Spearman's rank
      correlations were performed to identify associations between VEGF expression and
      MIB-1 LI. Fifteen dogs underwent postsurgical radiotherapy and were included in
      survival analysis. The effect of MIB-1 LI on survival was examined by Kaplan
      Meier and Cox proportional hazards regression procedures. RESULTS: Ki-67 staining
      was positive in 91% (64/70) and VEGF expression was detected in 96% (67/70).
      There was no significant association between VEGF expression and MIB-1 LI. MIB-1
      LI was not associated with survival. CONCLUSIONS AND CLINICAL IMPORTANCE: MIB-1
      antibody can be used to document cell proliferation in intracranial meningiomas
      in dogs, but does not predict outcome. No association between VEGF as a marker of
      angiogenesis and tumor proliferation was found. Angiogenesis might be a more
      important predictor of meningioma activity in dogs than is Ki-67.

PMID- 19175734
TI  - Double-blind placebo-controlled trial of adjuvant pamidronate with palliative
      radiotherapy and intravenous doxorubicin for canine appendicular osteosarcoma
      bone pain.
AB  - BACKGROUND: Canine osteosarcoma (OSA) causes focal malignant osteolysis leading
      to severe pain. Despite the documented efficacy of radiotherapy or IV
      aminobisphosphonates for managing cancer bone pain, their potential combined
      therapeutic value has not been reported in OSA-bearing dogs. HYPOTHESIS:
      Pamidronate combined with standardized palliative therapy will improve pain
      control and bone biologic effects in OSA-bearing dogs. ANIMALS: Fifty dogs with
      appendicular OSA treated with standardized palliative therapy and either
      pamidronate or sterile saline. METHODS: Randomized, prospective, double-blinded,
      placebo-controlled study. Treatment responses for dogs receiving standardized
      palliative therapy with (n = 26) or without (n = 24) adjuvant pamidronate were
      serially evaluated for changes in subjective pain scores, urine N-telopeptide
      (NTx) excretion, primary tumor relative bone mineral density (rBMD), and
      computerized pressure platform gait analysis. RESULTS: Median duration of
      subjective pain relief for dogs treated with adjuvant pamidronate or placebo was
      76 and 75 days, respectively (P= .39). Forty percent (20/50; pamidronate [11/26]
      and placebo [9/24]) of dogs experienced durable analgesia, defined by pain
      alleviation > or =112 days. For patients achieving durable pain control, dogs
      treated with pamidronate achieved greater reductions in NTx excretion and larger
      increases in rBMD compared with placebo controls. Changes in peak vertical force
      assessed by computerized pressure platform gait analysis correlated with pain
      alleviation in OSA-bearing dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Combining
      pamidronate with standardized palliative therapy is safe, but does not clearly
      improve pain alleviation. However, in dogs achieving durable pain control,
      adjuvant pamidronate appears to decrease focal bone resorption in the local tumor
      microenvironment.

PMID- 19175735
TI  - Prospective evaluation of coagulation in critically ill neonatal foals.
AB  - BACKGROUND: Coagulopathy is a potentially underrecognized complication of sepsis
      and septic shock in critically ill neonatal foals. HYPOTHESIS: Critically ill
      neonatal foals have abnormalities in coagulation that are associated with disease
      severity and outcome. ANIMALS: Foals <72 hours old admitted to a neonatal
      intensive care unit. METHODS: Prospective, observational study. Blood was
      collected at admission, 24, and 48 hours for platelet count, prothrombin time,
      activated partial thromboplastin time, antithrombin activity and concentrations
      of fibrin degradation products, and fibrinogen in plasma from all foals. RESULTS:
      Sixty-three foals were enrolled and classified as Septic Shock (12), Septic (28),
      and Other (23). At least 1 abnormal value was found in 18/28 (64%) samples from
      the Septic Shock group, 66/85 (78%) from the Septic group, and 30/59 (51%) from
      the Other group (P= .01). Coagulopathy (3 or more abnormal values) was present in
      7/28 (25%) samples in the Septic Shock group, 14/85 (16%) samples in the Septic
      group, and 3/59 (5%) samples in the Other group (P= .0028). Clinically detectable
      bleeding occurred in 8/12 (67%) Septic Shock cases, 11/28 (39%) Septic cases, and
      3/23 (13%) Other cases (P= .009). Foals in Septic Shock were 12.7 times more
      likely to have clinical evidence of bleeding than those in the Other group (95%
      CI 2.3-70, P= .004). Treatment with fluids or plasma did not have a detectable
      effect on coagulation values. CONCLUSIONS AND CLINICAL IMPORTANCE: Coagulopathy
      commonly occurs in critically ill neonatal foals, especially those with sepsis
      and septic shock.

PMID- 19175736
TI  - Thyroid function in anhidrotic horses.
AB  - BACKGROUND: This study was performed to determine whether anhidrotic horses have
      altered thyroid function compared with horses that sweat normally. HYPOTHESIS:
      Anhidrotic horses have normal thyroid function. ANIMALS: Ten client-owned horses
      with clinical signs of anhidrosis were paired with 10 horses living in the same
      environment that had normal sweat production. METHODS: Horses were diagnosed as
      having normal sweat production or being anhidrotic based on responses to
      intradermal injections of terbutaline and physiologic responses to lunging
      exercise. Control horses were selected from the same environment and matched as
      closely as possible to anhidrotic horses in terms of age, sex, breed, and
      athletic condition. Thyrotropin-releasing hormone (TRH) stimulation tests were
      performed in both horses at the same time, once in the summer or fall, and once
      again in winter. RESULTS: Anhidrotic horses produced less sweat in response to
      intradermal injections of terbutaline and exercise than did control horses. They
      also had greater increases in body temperature and respiratory rate in response
      to exercise. Resting concentrations of thyroid hormones and thyroid-stimulating
      hormone (TSH) were not different between anhidrotic and control horses. Thyroid
      hormone responses to TRH also were not different between the 2 groups of horses.
      However, anhidrotic horses had a significantly different TSH response to TRH
      compared with control horses, particularly in the winter. CONCLUSIONS AND
      CLINICAL IMPORTANCE: The biologic relevance of the altered TSH response to TRH in
      anhidrotic horses is uncertain, considering that TSH concentrations remained
      within previously reported normal ranges and thyroid hormone responses were not
      different between anhidrotic and control horses.

PMID- 19175737
TI  - Calprotectin in myeloid and epithelial cells of laminae from horses with black
      walnut extract-induced laminitis.
AB  - BACKGROUND: Laminar inflammation is one of the earliest events in equine
      laminitis. Calprotectin (CP), a Damage-Associated Molecular Pattern protein, is
      overexpressed in inflammatory conditions of human skin. HYPOTHESIS: CP is
      overexpressed in the laminar epidermis of horses with black walnut extract (BWE)
      induced laminitis. ANIMALS: Twenty adult horses. METHODS: Experimental study.
      Horses were allocated to one of 4 groups. BWE was administered to horses in 3
      groups, which were sampled 1.5, 3, and 12 hours (LAM) later. CP was visualized by
      immunohistochemistry. Laminar leukocyte counts and intensity of laminar
      epithelial staining were scored for all animals and statistically analyzed.
      RESULTS: Laminar epidermal CP signal was significantly increased (P= .02) at the
      LAM time point, compared with other groups. Rare leukocytes were detected in
      laminae with CP staining in CON group, but there were marked increases in number
      of leukocytes in BWE-treated groups (P= .003). Sequential hematoxylin and eosin
      staining demonstrated that the majority of CP-positive leukocytes were
      perivascular polymorphonuclear neutrophils (PMN) at each of the developmental
      time points. CP-positive PMN and mononuclear cells were detected in perivascular
      locations and close to the epidermal basement membrane in the LAM group.
      CONCLUSIONS AND CLINICAL IMPORTANCE: CP expression in the laminar epidermis
      occurs after extravasation of leukocytes, indicating that leukocyte emigration
      might be an initiating factor in laminar epithelial stress and inflammation in
      BWE-induced laminitis. These results indicate a possible role of CP in laminitis
      pathophysiology and laminar failure.

PMID- 19175738
TI  - Ralstonia pickettii septicemia in a dog with immune-mediated thrombocytopenia.

PMID- 19175739
TI  - Isolation or molecular detection of Bartonella henselae and Bartonella vinsonii
      subsp. berkhoffii from dogs with idiopathic cavitary effusions.

PMID- 19175740
TI  - Diagnosis of pulmonary arterio-venous fistula and persistent left cranial vena
      cava by 3-dimensional computed tomographic reconstruction.

PMID- 19175741
TI  - Seizure-like episodes in 3 cats with intermittent high-grade atrioventricular
      dysfunction.

PMID- 19175742
TI  - Eosinophilic granulomatous meningoencephalitis in 2 young Belgian Tervueren
      Shepherd dogs.

PMID- 19175743
TI  - Primary hyperparathyroidism and monoclonal gammopathy in a dog.

PMID- 19175744
TI  - Thrombosis of the pulmonary artery in a yearling thoroughbred colt.

PMID- 19175745
TI  - Outbreak of Streptococcus equi ssp. zooepidemicus polyserositis in an alpaca
      herd.

PMID- 19175749
TI  - Effect of spinal cord stimulation in a rodent model of post-operative ileus.
AB  - Post-operative ileus (POI) is a transient impairment of gastrointestinal (GI)
      transit that develops after abdominal surgery. The goal of this study was to
      investigate the effect of spinal cord stimulation (SCS) on gastric emptying and
      upper GI transit in a rat model of POI. All rats had an electrode placed on the
      dorsal surface of the spinal cord between the T(5) and T(8) segments. After
      recovery, gastric emptying and upper GI transit (geometric centre and head of
      meal) were assessed using a radiolabelled meal fed to each rat via oral gavage.
      In unanaesthetized rats, SCS (15, 25, 50, 100, 200 Hz, 0.2 ms at 90% motor
      threshold for 15 min) was performed immediately after the meal. The sham control
      group had no current applied. The naive group was without POI or SCS. Gastric
      emptying was significantly delayed in sham-stimulated rats with POI compared with
      naive controls (39.8 +/- 6.2%vs 76.5 +/- 4.9%, P < 0.001). In rats with POI that
      underwent SCS, there was a significant acceleration of gastric emptying to levels
      that resembled those of naive controls (65.1 +/- 7.4%, P < 0.05). However, while
      SCS did not normalize the geometric centre and head of the meal when compared
      with the naive group, it did significantly improve both parameters compared with
      the sham stimulation group. In summary, SCS normalizes gastric emptying and
      improves upper GI transit in a rodent model of POI. Further experiments are
      required to address the mechanism(s) by which SCS exhibits prokinetic activity.

PMID- 19175751
TI  - Zoospores of three Arctic laminariales under different UV radiation and
      temperature conditions: exceptional spectral absorbance properties and lack of
      phlorotannin induction.
AB  - Phlorotannins have often been considered to act as UV-protective compounds in
      zoospores of brown algae. However, only the absorption characteristics of
      zoospores under UV exposure have been determined and no data are available on the
      actual content of phlorotannins or on temperature-UV interactions. Therefore, we
      determined the absorbance spectra and the phlorotannin contents in zoospore
      suspensions of three Arctic species (Saccharina latissima, Laminaria digitata,
      Alaria esculenta), and in the media surrounding zoospores after exposure to
      different radiation (400-700, 320-700, 295-700 nm) and temperature (2-18 degrees
      C) conditions for 8 h. Absorption typical of phlorotannins with a maximum at 276
      nm was monitored in zoospore suspensions as well as in the media surrounding
      zoospores, but the results depended strongly on radiation treatments and on
      zoospore densities. Surprisingly, the content of UV-absorbing phlorotannins
      subsequent to different exposures did not change in any of the three species. The
      observed exceptional absorption properties could, therefore, not be related to
      phlorotannin contents. These findings are discussed in light of a strong
      phlorotannin investment from sporophytes during spore release and a minor UV
      protective role of phlorotannins for zoospores of Arctic kelp species.

PMID- 19175750
TI  - Interstitial cells of Cajal contain signalling molecules for transduction of
      nitrergic stimulation in guinea pig caecum.
AB  - Nitric oxide (NO) is an inhibitory signalling molecule in the gastrointestinal
      (GI) tract that is released from neurons and from leucocytes during inflammation.
      NO stimulates soluble guanylate cyclase (sGC), elevates cyclic guanosine 3',5'
      monophospate (cGMP), and subsequently activates cGMP-dependent protein kinase
      (PKG). Targets for NO in the guinea pig caecum were investigated by
      characterizing the cellular distribution of sGC, cGMP and PKG. Immunoreactivity
      for both isoforms of sGC, sGCalpha1 and sGCbeta1, was observed in the
      interstitial cells of Cajal (ICC) and enteric neurons in the tunica muscularis.
      Double labelling with anti-Kit and anti-sGC antibodies showed sGCalpha1 and
      sGCbeta1-like immunoreactivity (LI) in almost all intramuscular (IM) and
      myenteric ICC. Neuronal processes with neuronal NO synthase were closely apposed
      to ICC expressing sGC-LI. Cells with sGC-LI possessed ultrastructural features of
      ICC-IM: caveolae, close association with nerve bundles and contacts with smooth
      muscle cells (SMC). Sodium nitroprusside, added with the phosphodiesterase
      inhibitors (3-isobutyl-1-methylxanthine and zaprinast), enhanced cGMP-LI in
      almost all ICC and in some enteric neurons. Nerve stimulation also increased cGMP
      LI in ICC and enteric neurons. In contrast, no resolvable increase in cGMP-LI was
      observed in any cells when the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one was present. ICC and SMC also expressed PKG type I-LI. These
      data show that ICC express the downstream signalling molecules necessary to
      transduce nitrergic signals and activate inhibitory pathways and thus are primary
      targets for NO released from neurons and other cells in the GI tract.

PMID- 19175752
TI  - Fluorescence study on the interaction between hypericin and lens protein "alpha
      crystallin".
AB  - Hypericin has been reported as a potent photosensitizing agent exhibiting
      antiviral, antibacterial, antineoplastic activities. Although its photophysics
      and mode of action are strongly modulated by the binding protein, detailed
      information about its mechanism of interaction with possible cellular targets,
      including proteins, is still lacking. Previous in vitro studies demonstrated that
      hypericin can be uptaken by intact lens and is able to bind to the major lens
      protein "alpha-crystallin." In this study, the mechanism of interaction of this
      potent drug with alpha-crystallin was studied using the chemical denaturant
      guanidine hydrochloride (GdnHCl) and the hydrophobic surface probe, 8-anilino-1
      naphthalenesulfonic acid (ANS). Fluorescence measurements showed that the
      increased exposure of tryptophan resulting from partial unfolding of alpha
      crystallin incubated with 1.0 mol L(-1) of GdnHCl corresponds to the maximum
      accessibility of hydrophobic sites to ANS at the same GdnHCl concentration.
      Interestingly at this additional hydrophobicity of the protein, hypericin
      exhibited its maximum fluorescence intensity. This in vitro study implied that
      hydrophobic sites of alpha-crystallin play a significant role in its interaction
      with hypericin. The binding between alpha-crystallin and hypericin was found to
      be enhanced by partial perturbation of the protein.

PMID- 19175753
TI  - Maximizing tumor cell invasion.

PMID- 19175754
TI  - Induced cross-modal synaesthetic experience without abnormal neuronal
      connections.
AB  - Are the kinds of abnormal cross-modal interactions seen in synaesthesia or
      following brain damage due to hyperconnectivity between or within brain areas, or
      are they a result of lack of inhibition? This question is highly contested. Here
      we show that posthypnotic suggestion induces abnormal cross-modal experience
      similar to that observed in congenital grapheme-color synaesthesia. Given the
      short time frame of the experiment, it is unlikely that new cortical connections
      were established, so we conclude that synaesthesia can result from disinhibition
      between brain areas.

PMID- 19175755
TI  - The role of gender in mental-illness stigma: a national experiment.
AB  - The stigma of mental illness imposes substantial costs on both the individuals
      who experience mental illness and society at large. Understanding the
      psychological underpinnings of this stigma is therefore a matter of practical and
      theoretical significance. In a national, Web-based survey experiment, we
      investigated the role played by gender in moderating mental-illness stigma.
      Respondents read a case summary in which the gender of the person was
      orthogonally manipulated along with the type of disorder; the cases reflected
      either a male-typical disorder or a female-typical disorder. Results indicated
      that when cases were gender typical, respondents felt more negative affect, less
      sympathy, and less inclination to help, compared to when cases were gender
      atypical. This pattern can be explained by the fact that gender-typical cases
      were significantly less likely to be seen as genuine mental disturbances.

PMID- 19175756
TI  - Reward priority of visual target singletons modulates event-related potential
      signatures of attentional selection.
AB  - We examined visual search for color singleton targets, whose shape was
      discriminated. Critically, we varied the reward priority of singleton colors
      (correct fast performance was worth more bonus points for red singletons than for
      green singletons, or vice versa) to test whether event-related potential
      signatures of visual selection can be affected by distinct reward priorities for
      different target types, even when every target has to be selected for report. The
      N2pc component was earlier and larger for high- than for low-reward targets. This
      influence of reward on the N2pc correlated with the subject-by-subject impact of
      reward level on efficiency of behavioral performance. Later postselection
      processing was also affected by reward level. These results demonstrate that
      visual selection of task-relevant items is rapidly modulated by reward-related
      priorities, even when every target has to be selected for response.

PMID- 19175757
TI  - Genetic gating of human fear learning and extinction: possible implications for
      gene-environment interaction in anxiety disorder.
AB  - Pavlovian fear conditioning is a widely used model of the acquisition and
      extinction of fear. Neural findings suggest that the amygdala is the core
      structure for fear acquisition, whereas prefrontal cortical areas are given
      pivotal roles in fear extinction. Forty-eight volunteers participated in a fear
      conditioning experiment, which used fear potentiation of the startle reflex as
      the primary measure to investigate the effect of two genetic polymorphisms (5
      HTTLPR and COMTval158met) on conditioning and extinction of fear. The 5-HTTLPR
      polymorphism, located in the serotonin transporter gene, is associated with
      amygdala reactivity and neuroticism, whereas the COMTval158met polymorphism,
      which is located in the gene coding for catechol-O-methyltransferase (COMT), a
      dopamine-degrading enzyme, affects prefrontal executive functions. Our results
      show that only carriers of the 5-HTTLPR s allele exhibited conditioned startle
      potentiation, whereas carriers of the COMT met/met genotype failed to extinguish
      conditioned fear. These results may have interesting implications for
      understanding gene-environment interactions in the development and treatment of
      anxiety disorders.

PMID- 19175758
TI  - Fetal testosterone predicts sexually differentiated childhood behavior in girls
      and in boys.
AB  - Mammals, including humans, show sex differences in juvenile play behavior. In
      rodents and nonhuman primates, these behavioral sex differences result, in part,
      from sex differences in androgens during early development. Girls exposed to high
      levels of androgen prenatally, because of the genetic disorder congenital adrenal
      hyperplasia, show increased male-typical play, suggesting similar hormonal
      influences on human development, at least in females. Here, we report that fetal
      testosterone measured from amniotic fluid relates positively to male-typical
      scores on a standardized questionnaire measure of sex-typical play in both boys
      and girls. These results show, for the first time, a link between fetal
      testosterone and the development of sex-typical play in children from the general
      population, and are the first data linking high levels of prenatal testosterone
      to increased male-typical play behavior in boys.

PMID- 19175759
TI  - Survey of benzodiazepine and antidepressant use in outpatients with mood
      disorders in Japan.
AB  - Data on benzodiazepine use in mood disorders are still limited, especially among
      seniors. A cross-sectional review of psychotropic prescriptions in 948
      outpatients with mood disorders (405 male; mean +/- SD age, 52 +/- 17 years; age
      range, 16- 91 years) was conducted in Japan. The use of benzodiazepine-derivative
      anxiolytics was approximately 60% in all decades, including older patients,
      without a group difference. The frequent use of benzodiazepines is a cause for
      concern because they are not preferred treatment, given their well-known adverse
      effects especially in the elderly.

PMID- 19175760
TI  - Increased soluble tumor necrosis factor-alpha receptors in patients with major
      depressive disorder.
AB  - AIM: Several lines of evidence suggest that major depressive disorder is
      associated with an inflammatory status. Tumor necrosis factor-alpha has been
      investigated as a potential molecular target in mood disorders. Tumor necrosis
      factor-alpha exerts its activity through binding to specific cell membrane
      receptors named as TNFR1 and TNFR2. The aim of the present study was to
      investigate soluble plasma TNFR1 (sTNFR1) and TNFR2 levels (sTNFR2) in major
      depressive disorder patients. METHODS: Female outpatients with major depressive
      disorder (n = 30) were compared with a healthy control group (n = 19). Severity
      of depressive symptoms was evaluated on Beck Depression Inventory; post-traumatic
      stress disorder (PTSD) symptoms were evaluated on PTSD Checklist-Civilian
      Version; and childhood abuse and neglect on the Childhood Trauma Questionnaire.
      Plasma tumor necrosis factor-alpha and its soluble receptors were measured by
      ELISA. RESULTS: Patients had no changes in tumor necrosis factor-alpha
      concentrations but did have increased sTNFR1 (P < 0.001) and sTNFR2 (P < 0.001)
      levels compared to controls. Plasma level of sTNFR1 was positively predicted by
      age (B = 0.25, P = 0.05) and PTSD-like symptoms (B = 0.41, P = 0.002) and plasma
      levels of sTNFR2 by depression severity (B = 0.67, P < 0.001). CONCLUSIONS:
      Soluble tumor necrosis factor-alpha receptors could be reliable markers of
      inflammatory activity in major depression.

PMID- 19175762
TI  - Ethnicity and biological maturation in sports medicine research.

PMID- 19175761
TI  - Relationship of hypersensitivity to anxiety and depression in children with high
      functioning pervasive developmental disorders.
AB  - AIMS: Sensory-perceptual abnormalities, which include hyper- and hyposensitivity,
      have been identified by numerous researchers as prevalent in individuals with
      pervasive developmental disorders (PDD). Hypersensitivity has a greater impact on
      PDD patients' daily lives than hyposensitivity. The purpose of the present study
      was to clarify the relationship of hypersensitivity to anxiety, depression and
      other psychopathology in children with PDD. METHODS: Sixty-four children were
      divided into a hypersensitivity group (HG; n = 43) and a non-hypersensitivity
      group (non-HG; n = 21), and compared for anxiety, depression and other
      psychopathology on the Child Behavior Checklist (CBCL), State-Trait Anxiety
      Inventory for Children (STAIC) and Children's Depression Inventory (CDI).
      RESULTS: The HG group had significantly higher scores than the non-HG group in
      Total, Internalizing, and Somatic complaints on the CBCL. On STAIC, the mean sore
      of Total Score, State Score and Trait Score in the HG group tended to be higher
      than in the non-HG group, but the difference was not significant. The score on
      the CDI in the HG group was significantly higher than that in the non-HG group.
      CONCLUSION: PDD children with hypersensitivity have more serious
      psychopathologies, especially internalizing symptoms including depression.

PMID- 19175763
TI  - Implantation of scleral-fixated posterior chamber intraocular lenses in adults.
AB  - PURPOSE: To report the results of transscleral fixation of posterior chamber
      intraocular lenses in adults. METHODS: We carried out a retrospective analysis of
      91 eyes of 81 patients who underwent implantation of posterior chamber lenses
      with transscleral sutures between 1997 and 2006. The mean age of the patients was
      62 years (range 19-94 years). Sixty-eight eyes (74.7%) were aphakic at the time
      of surgery. In 10 patients (11.0%) an intracapsular cataract extraction and in
      six patients (6.6%) a pars plana lensectomy was performed prior to the fixation
      of the posterior chamber intraocular lens. In seven eyes (7.7%) a previously
      implanted IOL was removed. The mean follow-up was 36 months (range 6-116 months).
      RESULTS: The mean preoperative best corrected visual acuity (BCVA) was 0.37
      (range counting fingers to 1.0), which improved to 0.5 (range light perception to
      1.0) postoperatively. At the end of follow-up, BCVA was unchanged or improved in
      81 eyes (89.0%), reduced by 2 Snellen lines in four eyes (4.4%), and between
      finger counting and light perception in four eyes (4.4%). The most serious
      complication was suprachoroidal haemorrhage, which occurred in two eyes. Retinal
      detachment occurred in three eyes, all of which successfully reattached after
      surgery. Suture erosion or spontaneous dislocation caused by suture degradation
      or breakage was not seen. CONCLUSIONS: Secondary implantation of posterior
      chamber intraocular lenses with transscleral fixation is a reasonably safe
      procedure in adults, with relatively few serious complications. Even in patients
      with longterm follow-up, suture breakage was not seen.

PMID- 19175764
TI  - Sequence variations of the human MPDZ gene and association with alcoholism in
      subjects with European ancestry.
AB  - BACKGROUND: Mpdz gene variations are known contributors of acute alcohol
      withdrawal severity and seizures in mice. METHODS: To investigate the relevance
      of these findings for human alcoholism, we resequenced 46 exons, exon-intron
      boundaries, and 2 kilobases in the 5' region of the human MPDZ gene in 61
      subjects with a history of alcohol withdrawal seizures (AWS), 59 subjects with a
      history of alcohol withdrawal without AWS, and 64 Coriell samples from self
      reported nonalcoholic subjects [all European American (EA) ancestry] and compared
      with the Mpdz sequences of 3 mouse strains with different propensity to AWS. To
      explore potential associations of the human MPDZ gene with alcoholism and AWS,
      single SNP and haplotype analyses were performed using 13 common variants.
      RESULTS: Sixty-seven new, mostly rare variants were discovered in the human MPDZ
      gene. Sequence comparison revealed that the human gene does not have variations
      identical to those comprising Mpdz gene haplotype associated with AWS in mice. We
      also found no significant association between MPDZ haplotypes and AWS in humans.
      However, a global test of haplotype association revealed a significant difference
      in haplotype frequencies between alcohol-dependent subjects without AWS and
      Coriell controls (p = 0.015), suggesting a potential role of MPDZ in alcoholism
      and/or related phenotypes other than AWS. Haplotype-specific tests for the most
      common haplotypes (frequency > 0.05), revealed a specific high-risk haplotype (p
      = 0.006, maximum statistic p = 0.051), containing rs13297480G allele also found
      to be significantly more prevalent in alcoholics without AWS compared with
      nonalcoholic Coriell subjects (p = 0.019). CONCLUSIONS: Sequencing of MPDZ gene
      in individuals with EA ancestry revealed no variations in the sites identical to
      those associated with AWS in mice. Exploratory haplotype and single SNP
      association analyses suggest a possible association between the MPDZ gene and
      alcohol dependence but not AWS. Further functional genomic analysis of MPDZ
      variants and investigation of their association with a broader array of
      alcoholism-related phenotypes could reveal additional genetic markers of
      alcoholism.

PMID- 19175765
TI  - A unique program for cell death in xylem fibers of Populus stem.
AB  - Maturation of the xylem elements involves extensive deposition of secondary cell
      wall material and autolytic processes resulting in cell death. We describe here a
      unique type of cell-death program in xylem fibers of hybrid aspen (Populus
      tremula x P. tremuloides) stems, including gradual degradative processes in both
      the nucleus and cytoplasm concurrently with the phase of active cell-wall
      deposition. Nuclear DNA integrity, as determined by TUNEL (terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling) and Comet (single
      cell gel electrophoresis) assays, was compromised early during fiber maturation.
      In addition, degradation of the cytoplasmic contents, as detected by electron
      microscopy of samples fixed by high-pressure freezing/freeze substitution (HPF
      FS), was gradual and resulted in complete loss of the cytoplasmic contents well
      before the loss of vacuolar integrity, which is considered to be the moment of
      death. This type of cell death differs significantly from that seen in xylem
      vessels. The loss of vacuolar integrity, which is thought to initiate cell
      degradative processes in the xylem vessels, is one of the last processes to occur
      before the final autolysis of the remaining cell contents in xylem fibers. High
      resolution microarray analysis in the vascular tissues of Populus stem, combined
      with in silico analysis of publicly available data repositories, suggests the
      involvement of several previously uncharacterized transcription factors,
      ethylene, sphingolipids and light signaling as well as autophagy in the control
      of fiber cell death.

PMID- 19175766
TI  - The CRABS CLAW ortholog from California poppy (Eschscholzia californica,
      Papaveraceae), EcCRC, is involved in floral meristem termination, gynoecium
      differentiation and ovule initiation.
AB  - The Arabidopsis transcription factor CRABS CLAW (CRC) is a major determinant of
      carpel growth and fusion, and, in concert with other redundantly acting genes, of
      floral meristem termination. Its rice ortholog, however, has additional functions
      in specifying carpel organ identity. We were interested in understanding the
      history of gene function modulation of CRC-like genes during angiosperm
      evolution. Here, we report the identification and functional characterization of
      EcCRC, the Californica poppy (Eschscholzia californica) CRC ortholog. The
      downregulation of EcCRC by virus-induced gene silencing (VIGS) produces
      additional organ whorls that develop exclusively into gynoecia, resulting in a
      reiteration of the fourth whorl. Additionally, defects in carpel polarity and
      ovule initiation are apparent, and the observed phenotype is restricted to the
      gynoecium. Our results further show that the history of CRC-like genes during
      angiosperm evolution is characterized by gains of function, independent of
      duplication processes in this gene subfamily. Moreover, our data indicate that
      the ancestral angiosperm CRC-like gene was involved in floral meristem
      termination and the promotion of abaxial cell fate in the gynoecium, and that in
      the lineage leading to Arabidopsis, additional genes have been recruited to adopt
      some of these functions, resulting in a high degree of redundancy.

PMID- 19175768
TI  - Regulation of COP1 nuclear localization by the COP9 signalosome via direct
      interaction with CSN1.
AB  - COP1 and COP9 signalosome (CSN) are key regulators of plant light responses and
      development. Deficiency in either COP1 or CSN causes a constitutive
      photomorphogenic phenotype. Through coordinated actions of nuclear- and
      cytoplasmic-localization signals, COP1 can respond to light signals by
      differentially partitions between nuclear and cytoplasmic compartments. Previous
      genetic analysis in Arabidopsis indicated that the nuclear localization of COP1
      requires CSN, an eight-subunit heteromeric complex. However the mechanism
      underlying the functional relationship between COP1 and CSN is unknown. We report
      here that COP1 weakly associates with CSN in vivo. Furthermore, we report on the
      direct interaction involving the coiled-coil domain of COP1 and the N-terminal
      domain of the CSN1 subunit. In onion epidermal cells, expression of CSN1 can
      stimulate nuclear localization of GUS-COP1, and the N-terminal domain of CSN1 is
      necessary and sufficient for this function. Moreover, CSN1-induced COP1 nuclear
      localization requires the nuclear-localization sequences of COP1, as well as its
      coiled-coil domain, which contains both the cytoplasmic localization sequences
      and the CSN1 interacting domain. We also provide genetic evidence that the CSN1 N
      terminal domain is specifically required for COP1 nuclear localization in
      Arabidopsis hypocotyl cells. This study advances our understanding of COP1
      localization, and the molecular interactions between COP1 and CSN.

PMID- 19175767
TI  - A genetic network of flowering-time genes in wheat leaves, in which an
      APETALA1/FRUITFULL-like gene, VRN1, is upstream of FLOWERING LOCUS T.
AB  - To elucidate the genetic mechanism of flowering in wheat, we performed
      expression, mutant and transgenic studies of flowering-time genes. A diurnal
      expression analysis revealed that a flowering activator VRN1, an
      APETALA1/FRUITFULL homolog in wheat, was expressed in a rhythmic manner in leaves
      under both long-day (LD) and short-day (SD) conditions. Under LD conditions, the
      upregulation of VRN1 during the light period was followed by the accumulation of
      FLOWERING LOCUS T (FT) transcripts. Furthermore, FT was not expressed in a
      maintained vegetative phase (mvp) mutant of einkorn wheat (Triticum monococcum),
      which has null alleles of VRN1, and never transits from the vegetative to the
      reproductive phase. These results suggest that VRN1 is upstream of FT and
      upregulates the FT expression under LD conditions. The overexpression of FT in a
      transgenic bread wheat (Triticum aestivum) caused extremely early heading with
      the upregulation of VRN1 and the downregulation of VRN2, a putative repressor
      gene of VRN1. These results suggest that in the transgenic plant, FT suppresses
      VRN2 expression, leading to an increase in VRN1 expression. Based on these
      results, we present a model for a genetic network of flowering-time genes in
      wheat leaves, in which VRN1 is upstream of FT with a positive feedback loop
      through VRN2. The mvp mutant has a null allele of VRN2, as well as of VRN1,
      because it was obtained from a spring einkorn wheat strain lacking VRN2. The fact
      that FT is not expressed in the mvp mutant supports the present model.

PMID- 19175769
TI  - Drought tolerance in Arabidopsis is controlled by the OCP3 disease resistance
      regulator.
AB  - Water scarcity and corresponding abiotic drought stress is one of the most
      important factors limiting plant performance and yield. In addition, plant
      productivity is severely compromised worldwide by infection with microbial
      pathogens. Two of the most prominent pathways responsible for drought tolerance
      and disease resistance to fungal pathogens in Arabidopsis are those controlled by
      the phytohormones abscisic acid (ABA) and the oxylipin methyl jasmonate (MeJA),
      respectively. Here, we report on the functional characterization of OCP3, a
      transcriptional regulator from the homeodomain (HD) family. The Arabidopsis loss
      of-function ocp3 mutant exhibits both drought resistance and enhanced disease
      resistance to necrotrophic fungal pathogens. Double-mutant analysis revealed that
      these two resistance phenotypes have different genetic requirements. Whereas
      drought tolerance in ocp3 is ABA-dependent but MeJA-independent, the opposite
      holds true for the enhanced disease resistance characteristics. These
      observations lead us to propose a regulatory role of OCP3 in the adaptive
      responses to these two stresses, functioning as a modulator of independent and
      specific aspects of the ABA- and MeJA-mediated signal transduction pathways.

PMID- 19175770
TI  - Calcium depletion and calmodulin inhibition affect the import of nuclear-encoded
      proteins into plant mitochondria.
AB  - Many metabolic processes essential for plant viability take place in
      mitochondria. Therefore, mitochondrial function has to be carefully balanced in
      accordance with the developmental stage and metabolic requirements of the cell.
      One way to adapt organellar function is the alteration of protein composition.
      Since most mitochondrial proteins are nuclear encoded, fine-tuning of
      mitochondrial protein content could be achieved by the regulation of protein
      translocation. Here we present evidence that the import of nuclear-encoded
      mitochondrial proteins into plant mitochondria is influenced by calcium and
      calmodulin. In pea mitochondria, the calmodulin inhibitor ophiobolin A as well as
      the calcium ionophores A23187 and ionomycin inhibit translocation of nuclear
      encoded proteins in a concentration-dependent manner, an effect that can be
      countered by the addition of external calmodulin or calcium, respectively.
      Inhibition was observed exclusively for proteins translocating into or across the
      inner membrane but not for proteins residing in the outer membrane or the
      intermembrane space. Ophiobolin A and the calcium ionophores further inhibit
      translocation into mitochondria with disrupted outer membranes, but their effect
      is not mediated via a change in the membrane potential across the inner
      mitochondrial membrane. Together, our results suggest that calcium/calmodulin
      influences the import of a subset of mitochondrial proteins at the inner
      membrane. Interestingly, we could not observe any influence of ophiobolin A or
      the calcium ionophores on protein translocation into mitochondria of yeast,
      indicating that the effect of calcium/calmodulin on mitochondrial protein import
      might be a plant-specific trait.

PMID- 19175771
TI  - Shoot apical meristem function in Arabidopsis requires the combined activities of
      three BEL1-like homeodomain proteins.
AB  - In plants, most of the above-ground body is formed post-embryonically by the
      continuous organogenic potential of the shoot apical meristem (SAM). Proper
      function of the SAM requires maintenance of a delicate balance between the
      depletion of stem cell daughters into developing primordia and proliferation of
      the central stem cell population. Here we show that initiation and maintenance of
      the Arabidopsis SAM, including that of floral meristems, requires the
      combinatorial action of three members of the BELL-family of TALE homeodomain
      proteins, ARABIDOPSIS THALIANA HOMEOBOX 1 (ATH1), PENNYWISE (PNY) and POUND
      FOOLISH (PNF). All three proteins interact with the KNOX TALE homeodomain protein
      STM, and combined lesions in ATH1, PNY and PNF result in a phenocopy of stm
      mutations. Therefore, we propose that ath1 pny pnf meristem defects result from
      loss of combinatorial BELL-STM control. Further, we demonstrate that
      heterodimerization-controlled cellular localization of BELL and KNOX proteins
      involves a CRM1/exportin-1-mediated nuclear exclusion mechanism that is probably
      generic to control the activity of BELL and KNOX combinations. We conclude that
      in animals and plants corresponding mechanisms regulate the activity of TALE
      homeodomain proteins through controlled nuclear-cytosolic distribution of these
      proteins.

PMID- 19175772
TI  - Rapid analysis of poplar lignin monomer composition by a streamlined
      thioacidolysis procedure and near-infrared reflectance-based prediction modeling.
AB  - Determination of the physico-chemical attributes of plant cell walls, such as
      lignin content and composition, is of paramount importance in germplasm screening
      and for evaluating the results of plant breeding and genetic engineering. There
      are escalating needs for analyses to be robust, reproducible, accurate, and
      efficient. We have recently modified an established protocol for discrimination
      of lignin monomers, thioacidolysis, with the goal of increasing sample throughput
      while maintaining accuracy and reducing equipment load and consumption of
      reagents. Numerous methodological changes related to volume scaling, selection of
      the processing vessel, and sample handling were addressed. The revised protocol
      permitted rapid processing of some 50 or more samples per person per day. A
      direct comparison between methods using hybrid poplar (Populus alba x tremula)
      wood samples, resulted in quantities of p-hydroxyphenyl (H), guaiacyl (G), and
      syringyl (S) lignin monomers that were equivalent to those derived from the
      original protocol. The revised methodology was then applied to quickly generate
      phenotypic trait data from 267 hybrid poplar trees (including wild type and eight
      C4H::F5H transgenic lines), for the development of a near-infrared-based model
      for predicting the proportion of lignin monomers across a broad phenotypic range
      of S:G. The resulting partial least squares regression model performed well under
      full cross-validation, giving strong, linear relationships between actual and
      predicted monomer proportions, and very high predictive accuracy for the
      predominant G and S monomers. This research brings considerable refinement to the
      thioacidolysis procedure, and establishes a method for rapidly and accurately
      quantifying cell-wall lignin composition that could effectively be employed in
      routine phenotypic screening platforms.

PMID- 19175773
TI  - Thunderclap headache as an initial manifestation of phaeochromocytoma.

PMID- 19175774
TI  - Cerebrospinal fluid cytokine levels in migraine, tension-type headache and
      cervicogenic headache.
AB  - Cytokines have been measured in cerebrospinal fluid (CSF) from headache patients
      [infrequent episodic tension-type headache (TTH) and migraine with or without
      aura, all during attack, and cervicogenic headache] and compared with levels in
      pain-free individuals. Both proinflammatory [interleukin (IL)-1beta, tumour
      necrosis factor-alpha and monocyte chemoattractant protein-1 (MCP-1)] and anti
      inflammatory cytokines [IL-1 receptor antagonist (IL-1ra), IL-4, IL-10 and
      transforming growth factor-beta1 (TGF-beta1)] were included. There were
      significant group differences in IL-1ra, TGF-beta1 and MCP-1 in episodic TTH and
      migraine compared with controls, and a significant difference in MCP-1 between
      cervicogenic headache and migraine with aura. Intrathecal MCP-1 correlated with
      IL-1ra, IL-10 and TGF-beta1 in episodic TTH, and MCP-1 with IL-10 in migraine
      with aura. Cytokine increases were modest compared with those often accompanying
      serious neurological conditions, and may represent a mild response to pain. We
      believe this to be the first comparative study of CSF cytokine levels in
      connection with headache.

PMID- 19175775
TI  - Can intranasal corticosteroids cause migraine-like headache?
AB  - Intranasal corticosteroids (INCs) act predominantly locally and are considered to
      exert minimal systemic effects. On reviewing the international data collected in
      the World Health Organization's global pharmacovigilance programme an unexpected
      cluster was found of 38 case reports of migraine in suspected connection with
      INCs. These reports came from five countries (May 2007) and concerned six
      different drugs. In all reports the INC was the sole suspect drug. In nine cases
      re-exposure to the drug had taken place, leading to the recurrence of the event
      in eight of these patients. However, INCs are mainly used for rhinitis, and there
      is a known connection between rhinitis and migraine. Although representing only
      0.6% of the total of case reports, international pharmacovigilance data suggest
      that the use of INCs may cause or trigger migraine or migraine-like headache.
      Further study is needed to determine if the reported association is true or not
      and, if so, what the possible mechanism is.

PMID- 19175776
TI  - The GRIM2005 study of migraine consultation in France. III: Psychological
      features of subjects with migraine.
AB  - The objective of this analysis was to describe psychological and cognitive
      variables in subjects with migraine and to identify those associated with
      chronicity. Data were collected from 10 000 subjects during face-to-face
      interview. Subjects with episodic migraine (n = 1127) or chronic daily headache
      (n = 407) with migrainous features were identified using an algorithm based on
      the International Classification of Headache Disorders, 2nd edn classification.
      Data on headache impact was obtained with the Headache Impact Test-6, on
      psychological distress with the Hospital Anxiety and Depression Scale, on coping
      with the Coping Strategy Questionnaire catastrophizing score and the Brief COPE
      inventory, on illness perception with the Brief Illness Perception Questionnaire
      and on locus of control. Psychological variables associated with chronicity
      include perceived headache impact, psychological distress, the use of
      catastrophizing and avoidance coping strategies and an externalized locus of
      control. In conclusion, maladaptive coping strategies should be taken into
      account in the management of patients with migraine. Longitudinal studies will be
      necessary to address the causality of the relationship observed.

PMID- 19175777
TI  - Alcohol septal ablation in a young patient after aortic valve replacement.
AB  - A 38-year-old male presented with heart failure symptoms and was diagnosed with
      aortic valve endocarditis and underlying aortic stenosis in the absence of
      concentric hypertrophy or bicuspid aortic valve and underwent aortic valve
      replacement but continued to have symptoms which were then attributed to
      hypertrophic cardiomyopathy with dynamic left ventricular outflow tract
      obstruction. He was determined to be unsuitable for myomectomy and underwent
      successful alcohol septal ablation using transthoracic echocardiographic Doppler
      and continuous wave velocity monitoring without requiring to cross the aortic
      valve or to perform transatrial septostomy and left ventricular pressure
      monitoring. When crossing the aortic valve is a relative or absolute
      contraindication like in our index case, continuous Doppler velocity recording is
      a safe and effective alternative approach to monitor the outflow gradient while
      performing alcohol septal ablation.

PMID- 19175778
TI  - Dobutamine stress echocardiography identifies patients with angina and dynamic
      left ventricular outflow obstruction in physiological exercise.
AB  - BACKGROUND AND METHODS: To determine whether patients with no heart disease who
      develop dynamic left ventricular outflow obstruction (DLVOTO) during dobutamine
      echocardiography (DE) reproduce the phenomenon during exercise echocardiography
      (EE), DE and EE were performed in 78 patients (59 +/- 9 years) with effort angina
      and no alterations in SPECT. Thirty-eight (48.7%) patients had DLVOTO during DE
      and 15 (19.2%) during EE. This phenomenon during EE was reproducible in 39.4% of
      the patients with DLVOTO on DE, and 100% of the patients with DLVOTO during EE
      had it during DE. Independent factors predicting DLVOTO during EE were the LVOT
      diameter (OR 0.33 (0.14-0.74)) and the left ventricular (LV) mass index (OR 1.05
      (1.01-1.08)). No cardiovascular events were noted after 26+/-3 months. The
      reproducibility of DLVOTO during EE in patients with unexplained angina and with
      DLVOTO on DE is associated with the size of the LVOT and the LV mass index. The
      long-term prognosis is excellent.

PMID- 19175779
TI  - Prevalence, clinical correlates, and prognosis of discrete upper septal
      thickening on echocardiography: the Framingham Heart Study.
AB  - The upper interventricular septum may be prominent in elderly individuals, a
      finding referred to as discrete upper septal thickening (DUST). We examined the
      prevalence, clinical and echocardiographic correlates, and prognostic
      significance of DUST in a community-based sample. We evaluated Framingham Study
      participants who underwent routine echocardiography. In 3562 Framingham Study
      participants (mean age 58 years, 57% women), DUST was observed in 52
      participants. The clinical correlates of DUST were increasing age (odds ratio
      [OR] per 10 year increment 2.59, 95% confidence intervals [CI] 1.64-4.08) and
      systolic blood pressure (OR per SD increment 1.55, 95% CI 1.15-2.09). DUST was
      positively associated with left ventricular (LV) fractional shortening and mitral
      annular calcification but inversely with LV diastolic dimensions (P < 0.02 for
      all). On follow-up (mean 15 years), 732 individuals died (33 with DUST) and 560
      experienced a cardiovascular disease (CVD) event (18 with DUST). Adjusting for
      cardiovascular risk factors, DUST was not associated with CVD or mortality risk
      (P > 0.30 for both). The follow-up component of our study suggests that DUST is
      not independently associated with adverse prognosis.

PMID- 19175780
TI  - Giant condyloma acuminata of Buschke-Lowenstein: successful treatment with a
      combination of surgical excision, oral acitretin and topical imiquimod.
AB  - Human papillomavirus (HPV) is the most common sexually transmitted disorder in
      young, sexually active populations in the USA and Europe. Giant condyloma
      acuminatum (GCA) is a unique variant of condyloma acuminata, characterized by
      local aggressive behaviour despite benign histology. It carries a substantial
      risk of squamous cell carcinoma. Various treatments have been used, but response
      is often poor and recurrence rates high. We present a case of GCA successfully
      treated with a combination of surgical excision, oral acitretin and topical
      imiquimod. The diagnosis was based on histological examination,
      immunohistochemical analysis and in situ hybridization for HPV 6 and 11. We
      recommend a trial of oral retinoid and topical imiquimod in selected cases of
      GCA.

PMID- 19175781
TI  - Mutation of GJB2 in a Chinese patient with keratitis-ichthyosis-deafness syndrome
      and brain malformation.
AB  - OBJECTIVE: Keratitis-ichthyosis-deafness syndrome (KID) is a rare congenital
      disorder. Mutations in the GJB2 gene have recently been identified as the
      causative mutations of KID. AIM: To define the GJB2 mutation in a Chinese patient
      with KID and brain malformation. METHODS: Genomic DNA was extracted from
      peripheral blood and used to amplify the GJB2 gene. Direct sequencing and
      endonuclease digestion were used for mutation analysis. RESULTS: We identified a
      heterozygous missense mutation (D50N) in the GJB2 gene in this patient.
      CONCLUSIONS: These results indicate that KID syndrome in this patient was caused
      by a dominant mutation of GJB2.

PMID- 19175782
TI  - Methotrexate treatment in 13 children with severe plaque psoriasis.
AB  - BACKGROUND: Severe plaque psoriasis in childhood has a significant morbidity and
      can warrant the use of systemic agents, although there are no published clinical
      trials in this group. OBJECTIVES: We report a series of 13 children with severe
      plaque psoriasis treated with low-dose once-weekly methotrexate. METHODS: We
      reviewed the notes of all 13 children treated with low-dose methotrexate at
      Birmingham Children's Hospital. RESULTS: Of the 13 patients reviewed, 11
      responded with clearance of psoriasis, leaving small residual plaques. Five
      patients are currently maintained on methotrexate. Three patients needed two
      courses of methotrexate and one needed three courses, with treatment-free
      intervals of between 9 and 22 months. One patient stopped treatment due to rises
      in the results of liver function tests (LFTs) at 6 weeks, and one patient stopped
      the second course of methotrexate after two doses because of slightly raised
      baseline LFT results. There were no other adverse events. CONCLUSIONS: We propose
      that when carefully monitored, methotrexate can be a safe and efficacious
      treatment option for severe psoriasis in children as well as in adults. Obesity
      may be a relative contraindication, as associated nonalcoholic fatty liver
      disease is likely to increase hepatotoxicity.

PMID- 19175783
TI  - Incidence of chickenpox in young South Korean soldiers and correlation with
      atopic dermatitis.
AB  - BACKGROUND: In South Korea, military service is compulsory for all healthy young
      men and provides specific environmental factors, with groups working and living
      together in specific places for several years making varicella more transmissible
      to susceptible individuals. Studies of people serving in the South Korean
      military may provide information about the young adult male population in Korea.
      AIM: To determine the relationship between chickenpox and atopic dermatitis (AD)
      in young adults over a period of 3 years. METHODS: The computerized database of
      the Armed Forces Medical Command was examined to identify the number of reported
      cases of chickenpox, AD, and AD associated with chickenpox. RESULTS: In total,
      588 cases of chickenpox (183, 182 and 223 in the periods November 2004 to October
      2005, November 2005 to October 2006, and November 2006 to October 2007,
      respectively) were reported. A greater number of patients were found to be
      infected with chickenpox in January and November, with fewer patients in August
      and September (P < 0.0001). Within the same periods, 1890, 2417 and 2779 patients
      diagnosed with AD were recorded in the Defense Medical Information System. Only 3
      of 588 patients with chickenpox also had AD (0.5%). CONCLUSION: In this
      population-based study, the epidemiological trend of chickenpox and AD over a
      period of 3 years within the military personnel of South Korea is shown.

PMID- 19175784
TI  - A randomized controlled trial to evaluate short-term treatment with eosin vs.
      topical steroids in psoriasis.
AB  - BACKGROUND: The therapeutic effects of some histological staining agents on
      psoriasis have been reported in the past. One of these agents is eosin, which is
      still currently used in routine treatment, although it has never been formally
      tested in a randomized controlled trial. Aim. To compare treatment with eosin in
      patients with moderate to severe psoriasis vs. short-course topical steroid, a
      well-defined, evidence-based treatment. METHODS: A randomized trial was designed
      and conducted. The Skindex-29 and General Health Questionnaire (GHQ)-12
      questionnaires, and Psoriasis Activity and Disease Index (PASI) were used before
      treatment in 43 patients. Five days after treatment, PASI was measured again.
      RESULTS: Five days after treatment, a significant mean reduction of PASI was
      observed in both groups: 6.8 (95% CI 5.5-8) for eosin, and 5.2 (3.2-7.1) for
      steroids. The difference between the two groups was not significant (P = 0.161).
      CONCLUSIONS: Eosin has a short-term effect similar to topical steroids. The low
      cost of eosin treatment and its limited collateral effects suggest that eosin
      could be an effective steroid-sparing agent in the initial phase of psoriasis
      treatment.

PMID- 19175785
TI  - Nicotinamide and its metabolite N-methylnicotinamide increase skin vascular
      permeability in rats.
AB  - BACKGROUND: It has been suggested that topically applied nicotinamide and its
      metabolite N-methylnicotinamide (NMN(+)) might be useful agents for treatment of
      dermatological disorders such as acne vulgaris and rosacea. AIM: This study aimed
      to find out if the mechanism of these therapeutic effects depends on their
      vascular effects, by investigating if nicotinamide and NMN(+) are able to
      influence vascular permeability of the vessels in the skin on the back of Wistar
      rats. METHODS AND RESULTS: A dose-dependent increase in vascular permeability was
      seen in rats treated intradermally with nicotinamide and NMN(+). Interestingly, a
      significantly stronger effect of NMN(+) compared with nicotinamide was evident.
      Increased vascular permeability in rats treated with 0.5% NMN(+) ointment was
      seen. Moreover, indomethacin, a cyclo-oxygenase 1 and 2 inhibitor and N(G)-nitro
      L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, reduced
      the observed effects of nicotinamide and NMN(+). CONCLUSIONS: This study provides
      direct in vivo evidence that nicotinamide and its metabolite NMN(+) increase skin
      vascular permeability in rats by a mechanism that may involve NO and
      prostaglandins.

PMID- 19175786
TI  - Chondrodermatitis nodularis chronica helicis in monozygotic twins.
AB  - Chondrodermatitis nodularis chronica helicis (CNCH) is a benign inflammatory
      nodule of the helix. Patients report severe tenderness upon pressure. Commonly
      seen in middle-aged men, there are no reports of this disease in twins. We report
      middle-aged male monozygotic twins who simultaneously developed CNCH. This
      suggests, but does not prove, the possibility of a hereditary factor in the
      pathogenesis of CNCH.

PMID- 19175787
TI  - Cutaneous lymphangiectasia associated with photoageing and topical corticosteroid
      application.
AB  - We report the case of a 69-year-old man with a history of multiple erythematous
      bullae on both forearms, which had been present for about 1 month. The lesions
      appeared after several years of topical corticosteroid application and
      photoageing. A biopsy revealed lymphangiectasia with solar elastosis and increase
      in the ratio of elastic to collagen fibres in the dermis. We suggest that this
      patient's lymphangiectasia resulted from abnormal structure and function of the
      dermis due to photoageing and steroid-related atrophy.

PMID- 19175788
TI  - Granuloma faciale treated successfully with topical tacrolimus.

PMID- 19175789
TI  - Interleukin 8 as a chemoattractant for neutrophil granulocytes in toxic epidermal
      necrolysis lesions.

PMID- 19175790
TI  - Distribution and activity of diazotrophs in the Eastern Equatorial Atlantic.
AB  - The gene abundance and gene expression of six diazotroph populations from the
      Eastern Equatorial Atlantic in June 2007 were examined using nifH gene
      quantitative polymerase chain reaction (q PCR) methods. Of all the diazotrophs,
      Trichodesmium spp. was the most abundant with the highest number of gene copies
      in the Gulf of Guinea. Trichodesmium also had the highest nitrogenase gene
      transcript abundance overall with the maximum in samples collected at the equator
      and in waters influenced by the Congo River plume (> 10(5) cDNA nifH copies l(
      1)). Both cyanobacterial unicellular groups (A and B) were detected, where group
      A was the second most abundant in surface samples, in particular at the stations
      along the equator. Transcript abundance for group A, however, was at the
      detection limit and suggests that it was not actively fixing N(2). Trichodesmium
      and group B nifH gene abundances co-varied (P < 0.0001). Richelia associated with
      Hemiaulus hauckii diatoms were detected in 9 of 10 surface samples and the
      highest abundances (> 10(4)nifH copies l(-1)) were found north-west of the Congo
      River plume. In contrast, the Calothrix symbionts (het-3) of Chaetoceros had low
      abundances at the surface, but were present at 3.7 x 10(4)nifH copies l(-1) at 40
      m depth in the equatorial upwelling. This is the first report of the Calothrix
      symbiont in the Atlantic Ocean. This is also the first report of nifH gene copy
      and transcript abundance in an Equatorial upwelling zone. Although the number of
      gene copies for Richelia associated with Rhizosolenia were the lowest, the
      transcript abundance were high (9.4 x 10(1)-1.8 x 10(4) cDNA nifH copies l(-1))
      and similar to that of Trichodesmium. The distribution of the diazotroph groups,
      especially the three strains of symbiotic cyanobacteria, was different, and
      appeared largely controlled by riverine inputs and upwelling.

PMID- 19175791
TI  - Adaptation of protein expression by Escherichia coli in the gastrointestinal
      tract of gnotobiotic mice.
AB  - The gastrointestinal tract of mammals is inhabited by several hundred bacterial
      species. While the effects of the gut microbiota upon the host have been widely
      studied, the microbial response to host factors has only recently attracted
      attention. In order to investigate the influence of the host on the physiology of
      gastrointestinal bacteria, a simplified model of host-bacteria interaction was
      created by associating germfree mice with commensal Escherichia coli. Here we
      demonstrate the feasibility of analysing the bacterial response to the conditions
      in the digestive system by a proteomics-based approach. Two-dimensional gel
      electrophoresis (2D-GE) followed by electrospray ionization-tandem mass
      spectrometry (ESI-MS/MS) was used to identify bacterial proteins from caecal and
      faecal samples. In a set of 60 arbitrarily chosen spots of stably and
      differentially expressed proteins, 50 different bacterial proteins were
      identified. Their ascribed functions suggest that the host-associated bacteria
      adapt their metabolism to the conditions in the intestine by utilizing arginine,
      asparagine and aspartate as well as glucose/galactose, ribose, maltose,
      glucuronate, galacturonate and gluconate as substrates. Thirteen proteins not
      previously detected on 2D-gels and 10 proteins with unknown or poorly
      characterized physiological function were identified, while the existence of
      three proteins had so far only been inferred from predictions or by homology.

PMID- 19175792
TI  - Impaired myelopoiesis in mice lacking the repressors of translation initiation,
      4E-BP1 and 4E-BP2.
AB  - We investigated the role of two repressors of translation initiation in
      granulocytic differentiation using mice with a null mutation in the 4E-BP1 gene
      or with a null mutation in the 4E-BP2 gene. We show that 4E-BP1(-/-) and 4E-BP2(
      /-) mice exhibit an increased number of immature granulocytic precursors,
      associated with a decreased number of mature granulocytic elements compared with
      wild-type mice, which is suggestive of an impaired granulocytic differentiation.
      Clonogenetic analyses revealed a reduced number of granulocytic colonies and
      concomitant increase in granulo-monocytic colonies in 4E-BP(-/-) mice. Finally, a
      slight expansion of monocytic cells was observed in the 4E-BP2(-/-) mice. In
      contrast, we did not observe any significant difference in thymocyte maturation
      in these mice. These results, together with the fact that 4E-BPs are markedly
      induced during granulo-monocytic differentiation of myeloid cells in vitro,
      highlight the pivotal role of 4E-BP1 and 4E-BP2 in the early phases of
      myelopoiesis. These results represent the first in vivo evidence of the
      involvement of translation in the early phases of granulo-monocytic
      differentiation and further extend the role of translation in haematopoietic
      differentiation.

PMID- 19175793
TI  - The lectin Jacalin induces human B-lymphocyte apoptosis through glycosylation
      dependent interaction with CD45.
AB  - It has been well established that CD45 is a key receptor-type protein tyrosine
      phosphatase (PTPase) regulating Src-family protein tyrosine kinase (Src-PTK) in T
      and B lymphocytes. However, precisely how CD45 exerts its effect in these
      lymphocytes remains controversial. We recently reported that Jacalin, an alpha-O
      glycoside of the disaccharide Thomsen-Friedenreich antigen-specific lectin from
      jackfruit seeds, caused marked T-cell activation in response to T-cell receptor
      ligation and CD28 costimulation by binding to CD45. On extending the reported
      research, we found that CD45 and isoforms are major Jacalin receptors on B
      lymphocytes, and that the glycosylation of CD45 is involved in the interaction of
      Jacalin with the PTPase. In contrast to Jacalin-stimulated T-cell activation, we
      found that Jacalin induced human B-lymphocyte apoptosis, resulting in calcium
      mobilization and calpain activation, suggesting that the calcium-calpain pathway
      may mediate the Jacalin-induced apoptosis. Importantly, the apoptosis was
      effectively blocked by a specific CD45 PTPase inhibitor, indicating that Jacalin
      induces human B-lymphocyte apoptosis through CD45 triggering. Furthermore, we
      found that Jacalin significantly increased the C-terminal inhibitory tyrosine
      (Tyr507) phosphorylation of Src-PTK Lyn, one of the major substrates of CD45
      PTPase, and this effect was also observed on incubation of B lymphocytes with the
      specific CD45 PTPase inhibitor, suggesting that Jacalin stimulation results in
      increasing C-terminal tyrosine phosphorylation of the kinase through inhibition
      of CD45 tyrosine phosphatase activity in human B lymphocytes. Therefore, the down
      modulation of Lyn kinase may play a role in the regulation of B-lymphocyte
      viability.

PMID- 19175794
TI  - The acute-phase response impairs host defence against Enterococcus faecium
      peritonitis.
AB  - Enterococcus faecium is an emerging pathogen that causes infections in
      hospitalized patients with various co-morbid diseases. These underlying diseases
      are often associated with an acute-phase response that renders patients
      vulnerable to nosocomial infections. To study the influence of the acute-phase
      response induced by sterile tissue injury on host defence against E. faecium,
      mice were injected subcutaneously with either turpentine or casein 1 day before
      intraperitoneal infection with E. faecium. Control mice were subcutaneously
      injected with saline or sodium bicarbonate, respectively. Turpentine and casein
      induced an acute-phase response as reflected by increases in the plasma
      concentrations of interleukin-6, serum amyloid P and C3. A pre-existent acute
      phase response in mice was associated with a strongly reduced capacity to clear
      E. faecium, resulting in prolonged bacteraemia for several days. The inflammatory
      response to E. faecium was impaired in mice with an acute-phase response, as
      shown by reduced capacity to mount a neutrophilic leucocytosis in peripheral
      blood and by decreased local cytokine concentrations. These data indicate that
      the acute-phase response impairs host defence against E. faecium, suggesting that
      this condition may contribute to the increased vulnerability of critically ill
      patients to enterococcal infections.

PMID- 19175795
TI  - Variable antigen uptake due to different expression of the macrophage mannose
      receptor by dendritic cells in various inbred mouse strains.
AB  - Antigen uptake by dendritic cells is essential for the induction of antigen
      specific T-cell responses. Here, we investigate the ability of dendritic cells
      from different mouse strains to endocytose antigens. The uptake of different
      fluorescently labelled soluble antigens by bone marrow-derived dendritic cells
      from BALB/c, C57BL/6 and C3H/HeN mice was analysed by flow cytometry. Using
      transferrin as a specific marker for clathrin-mediated endocytosis, we observed
      no significant differences of transferrin uptake by dendritic cells from BALB/c,
      C57BL/6 and C3H/HeN mice. Similar results were obtained by analysing
      macropinocytosis with lucifer yellow. In contrast, analysing the uptake of
      ovalbumin, which is predominantly mediated by clathrin-mediated endocytosis via
      the macrophage mannose receptor, we found that dendritic cells from C3H/HeN mice
      take up three- to fivefold more ovalbumin than dendritic cells from BALB/c or
      C57BL/6 mice. Blocking the uptake of ovalbumin via the macrophage mannose
      receptor by using mannan led to a comparable uptake of ovalbumin by dendritic
      cells from all three mouse strains. Consistently, dendritic cells from C3H/HeN
      mice displayed significantly increased expression of the macrophage mannose
      receptor compared to dendritic cells from BALB/c or C57BL/6 mice. In conclusion,
      receptors involved in antigen uptake such as the macrophage mannose receptor may
      be differentially expressed and may explain variations of T-cell responses after
      vaccination in different individuals.

PMID- 19175796
TI  - Glycogen synthase kinase-3 negatively regulates anti-inflammatory interleukin-10
      for lipopolysaccharide-induced iNOS/NO biosynthesis and RANTES production in
      microglial cells.
AB  - The inflammatory effects of glycogen synthase kinase-3 (GSK-3) have been
      identified; however, the potential mechanism is still controversial. In this
      study, we investigated the effects of GSK-3-mediated interleukin-10 (IL-10)
      inhibition on lipopolysaccharide (LPS)-induced inflammation. Treatment with GSK-3
      inhibitor significantly blocked LPS-induced nitric oxide (NO) production as well
      as inducible NO synthase (iNOS) expression in BV2 murine microglial cells and
      primary rat microglia-enriched cultures. Using an antibody array and enzyme
      linked immunosorbent assay, we found that GSK-3-inhibitor treatment blocked LPS
      induced upregulation of regulated on activation normal T-cell expressed and
      secreted (RANTES) and increased IL-10 expression. The time kinetics and dose
      response relations were confirmed. Reverse transcription-polymerase chain
      reaction showed changes on the messenger RNA level as well. Inhibiting GSK-3
      using short-interference RNA, and transfecting cells with dominant-negative GSK
      3beta, blocked LPS-elicited NO and RANTES expression but increased IL-10
      expression. In contrast, GSK-3beta overexpression upregulated NO and RANTES but
      downregulated IL-10 in LPS-stimulated cells. Treating cells with anti-IL-10
      neutralizing antibodies to prevent GSK-3 from downregulating NO and RANTES showed
      that the anti-inflammatory effects are, at least in part, IL-10-dependent. The
      involvement of Akt, extracellular signal-regulated kinase, p38 mitogen-activated
      protein kinase and nuclear factor-kappaB that positively regulated IL-10 was
      demonstrated. Furthermore, inhibiting GSK-3 increased the nuclear translocation
      of transcription factors, that all important for IL-10 expression, including
      CCAAT/enhancer-binding protein beat (C/EBPbeta), C/EBPdelta, cAMP response
      binding element protein and NF-kappaB. Taken together, these findings reveal that
      LPS induces iNOS/NO biosynthesis and RANTES production through a mechanism
      involving GSK-3-mediated IL-10 downregulation.

PMID- 19175798
TI  - RNA interference of STAT6 rapidly attenuates ongoing interleukin-13-mediated
      events in lung epithelial cells.
AB  - Signal transducer and activator of transcription 6 (STAT6) expression in lung
      epithelial cells plays a central role in asthma pathogenesis, with its activation
      driving the development of airway hyper-reactivity and local inflammation.
      Therefore, inhibition of local STAT6 expression provides a rationale for
      therapeutic intervention in bronchial asthma. Given the absence of specific
      inhibitory drugs, we tested the ability of small interfering RNAs (siRNAs) to
      target STAT6 gene expression through the molecular process of RNA interference
      (RNAi). At pico-molar concentrations, STAT6-specific siRNAs potently inhibited
      STAT6 mRNA expression in lung epithelial cells (50% inhibitory concentration
      range = 134-861 pm) without inducing cellular interferon responses. Detectable
      STAT6 protein expression was rapidly abolished within 48 hr of treatment (t(1/2)
      range = or < 12-37 hr) and this was unaffected by pretreatment with STAT6
      activating cytokines. Furthermore, STAT6 suppression by RNAi produced downstream
      functional inhibitory effects in that interleukin (IL)-13- or IL-4-driven eotaxin
      chemokine family [chemokine (C-C motif) ligand 11 (CCL11), CCL24 and CCL26] mRNA
      expression was markedly inhibited. Induction of detectable CCL26 protein
      synthesis was completely ablated by pretreating cells with STAT6-specific siRNA.
      The therapeutic potential of this approach is further demonstrated by novel
      findings that cells pre-exposed to IL-13 or IL-4 and subsequently treated with
      STAT6-targeting siRNA exhibited a rapid and significant attenuation of ongoing
      CCL26 protein expression, suggesting that chronic asthma-associated lung
      inflammation will be responsive to this approach.

PMID- 19175797
TI  - Increased cyclooxygenase activity impairs apoptosis of inflammatory neutrophils
      in mice lacking gelatinase B/matrix metalloproteinase-9.
AB  - Matrix metalloproteinase-9 (MMP-9)/gelatinase B plays an important role in
      neutrophil infiltration during inflammation and cyclooxygenases (COX-1 and COX-2)
      and their products are important regulators of inflammation. Recently, we
      reported that a genetic lack of MMP-9 impairs neutrophil infiltration during
      early zymosan-induced peritonitis but at later stages (> 24 hr) neutrophils
      persist in the peritoneal cavity. Here we show that this is the result of
      impaired apoptosis of MMP-9(-/-)-derived leucocytes. As enhanced COX-1 expression
      was reported in MMP-9(-/-) mice, we evaluated the hypothesis that altered COX
      expression induced the above phenomenon as COX-dependent prostaglandins can act
      either anti-apoptotically (PGE(2)) or pro-apoptotically (PGD(2)). The current
      data demonstrate that messenger RNA and protein expression of both COX isoforms
      and their activities are increased in MMP-9(-/-) mice during late peritonitis.
      Application of selective COX inhibitors revealed enhanced COX-1-dependent PGE(2)
      production and impaired COX-2-dependent PGD(2) synthesis in MMP-9(-/-) mice. Most
      importantly, inhibition of COX-1 abolished prolonged neutrophil accumulation in
      the peritoneal cavity of MMP-9(-/-) mice and increased apoptosis of inflammatory
      leucocytes. Similarly, weaker apoptosis of MMP-9(-/-) bone marrow neutrophils
      treated in vitro with zymosan was reversed by COX-1 inhibition. In conclusion,
      enhanced COX-1 expression is responsible for persistent neutrophil presence in
      the peritoneum of MMP-9(-/-) mice because of increased synthesis of anti
      apoptotic PGE(2). In non-transgenic mice, however, inflammatory leucocytes die
      apoptotically in the late stages of peritonitis as a result of COX-2-dependent
      PGD(2) activity. Overall, we show a dependence of COX expression on the presence
      of MMP-9.

PMID- 19175799
TI  - Role of pathogenic T cells and autoantibodies in relapse and progression of
      myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis in
      LEW.1AV1 rats.
AB  - Accumulating evidence suggests that T cells and autoantibodies reactive with
      myelin oligodendrocyte glycoprotein (MOG) play a critical role in the
      pathogenesis of multiple sclerosis (MS). In the present study, we have tried to
      elucidate the pathomechanisms of development and progression of the disease by
      analysing T cells and autoantibodies in MOG-induced rat experimental autoimmune
      encephalomyelitis (EAE), which exhibits various clinical subtypes mimicking MS.
      Analysis using overlapping peptides revealed that encephalitogenic epitopes
      resided in peptide 7 (P7, residue 91-108) and P8 (residue 103-125) of MOG.
      Immunization with MOGP7 and MOGP8 induced relapsing-remitting or secondary
      progressive EAE. T cells taken from MOG-immunized and MOGP7-immunized rats
      responded to MOG and MOGP7 and sera from MOG-immunized rats reacted to MOG and
      MOGP1. Significant epitope spreading was not observed at either T-cell or
      antibody levels. Interestingly, sera from MOGP7-immunized rats with clinical
      signs did not react to MOG and MOG peptides throughout the observation period,
      suggesting that disease development and relapse in MOGP7-induced EAE occur
      without autoantibodies. However, MOGP7 immunization with adoptive transfer of
      anti-MOG antibodies aggravated the clinical course of EAE only slightly. Analysis
      of antibodies against conformational epitope (cme) suggests that anti-MOG(cme)
      may play a role in the pathogenicity of anti-MOG antibodies. Collectively, these
      findings demonstrated that relapse of a certain type of MOG-induced EAE occurs
      without autoantibodies but that autoantibodies may play a role in disease
      progression. Relapses and the progression of MS-mimicking EAE are differently
      immunoregulated so immunotherapy should be designed appropriately on the basis of
      precise information.

PMID- 19175800
TI  - Pathways regulating lipopolysaccharide-induced neutrophil survival revealed by
      lentiviral transduction of primary human neutrophils.
AB  - Human neutrophils express Toll-like receptor 4 (TLR4) at low levels, and the role
      of this receptor in neutrophil responses to microbial stimuli has been
      questioned. Genetic manipulation of these cells to enable the study of the role
      of proteins such as TLR4 in their function is challenging. Here, we show that
      primary human neutrophils rapidly express novel proteins such as enhanced green
      fluorescent protein (eGFP) after transduction with lentivirus. Stimulation of
      transduced neutrophils with lipopolysaccharide (LPS) resulted in increased cell
      survival, which was inhibited when neutrophils were transduced with a lentivirus
      encoding a dominant negative (dn) TLR4 protein. LPS-induced survival was also
      inhibited by lentiviruses encoding dnMyD88 or a truncated TRIF (Toll/interleukin
      1R homologous domain-containing adapter protein inducing interferon-beta)
      molecule, whilst, in contrast, neutrophil survival was enhanced by overexpression
      of kinase-mutated interleukin-1 receptor-associated kinase 1 (kmIRAK-1), which
      activated nuclear factor (NF)-kappaB. These studies provide proof of the role of
      TLR4 in human neutrophil biology, have begun to elucidate TLR-dependent pathways
      regulating neutrophil survival, and demonstrate that neutrophils can be
      genetically manipulated to enhance or inhibit survival.

PMID- 19175801
TI  - Bacterial lipopeptide triggers massive albuminuria in murine lupus nephritis by
      activating Toll-like receptor 2 at the glomerular filtration barrier.
AB  - What are the molecular mechanisms of bacterial infections triggering or
      modulating lupus nephritis? In nephritic MRL(lpr/lpr) mice, transient exposure to
      bacterial cell wall components such as lipopeptide or lipopolysaccharide (LPS)
      increased splenomegaly, the production of DNA autoantibodies, and serum
      interleukin (IL)-6, IL-12 and tumour necrosis factor (TNF) levels, and aggravated
      lupus nephritis. Remarkably, bacterial lipopeptide induced massive albuminuria in
      nephritic but not in non-nephritic mice. This was associated with down-regulation
      of renal nephrin mRNA and redistribution from its normal localization at foot
      processes to the perinuclear podocyte area in nephritic MRL(lpr/lpr) mice.
      Bacterial lipopeptide activates Toll-like receptor 2 (TLR2), which we found to be
      expressed on cultured podocytes and glomerular endothelial cells. TNF and
      interferon (IFN)-gamma induced TLR2 mRNA and receptor expression in both cell
      types. Albumin permeability was significantly increased in cultured podocytes and
      glomerular endothelial cells upon stimulation by bacterial lipopeptide. LPS also
      induced moderate albuminuria. In summary, bacterial lipopeptide and LPS can
      aggravate glomerulonephritis but only lipopeptide potently induces severe
      albuminuria in MRL(lpr/lpr) mice.

PMID- 19175803
TI  - Forensic podiatry: a review.
AB  - Abstract Although forensic podiatry has been around for a number of years, it has
      only recently become formally established through research being carried out in
      the field and resultant professional and regulatory board acceptance. A critical
      review of forensic podiatry is presented, covering its' history, areas of
      practice and evidence base. The need for further research is recognized, which
      will, in turn bring about further practice development in this specialized area.

PMID- 19175802
TI  - Plasma and memory B-cell kinetics in infants following a primary schedule of CRM
      197-conjugated serogroup C meningococcal polysaccharide vaccine.
AB  - The induction of persistent protective levels of pathogen-specific antibody is an
      important goal of immunization against childhood infections. However, antibody
      persistence is poor after immunization in infancy versus later in life. Serogroup
      C meningococci (MenC) are an important cause of bacteraemia and meningitis in
      children. The use of protein-polysaccharide conjugate vaccines against MenC has
      been associated with a significant decline in the incidence of invasive disease.
      However, vaccine effectiveness is negligible by more than 1 year after a three
      dose priming series in infancy and corresponds to a rapid decline in antibody
      following an initial immune response. The cellular mechanisms underlying the
      generation of persistent antibody in this age group are unclear. An essential
      prelude to larger studies of peripheral blood B cells is an understanding of B
      cell kinetics following immunization. We measured MenC- and diphtheria-specific
      plasma and memory B-cell kinetics in infants receiving a CRM(197) (cross-reactive
      material; mutant diphtheria toxoid)-conjugated MenC vaccine at 2, 3 and 4 months
      of age. Plasma cell responses were more delayed after the first dose when
      compared with the rapid appearance of plasma cells after the third dose. Memory B
      cells were detectable at all time-points following the third dose as opposed to
      the low frequency seen following a first dose. This study provides data on B-cell
      kinetics following a primary schedule of immunization in young infants upon which
      to base further studies of the underlying cellular mechanism of humoral immunity.

PMID- 19175804
TI  - Oxygen, the Janus gas; its effects on human placental development and function.
AB  - The accumulation of oxygen in the earth's atmosphere enabled metabolic pathways
      based on high-energy electron transfers that were capable of sustaining complex
      multicellular organisms to evolve. This advance came at a price, however, for the
      high reactivity of oxygen posed a major challenge as biological molecules became
      susceptible to oxidative damage, resulting in potential loss of function. Many
      extant physiological systems are therefore adapted, and homeostatically
      regulated, to supply sufficient oxygen to meet energy demands whilst also
      protecting cells, and mitochondria in particular, from excessive concentrations
      that could lead to oxidative damage. The invasive form of implantation displayed
      by the human conceptus presents particular challenges in this respect. During the
      first trimester, the conceptus develops in a low oxygen environment that favours
      organogenesis in the embryo, and cell proliferation and angiogenesis in the
      placenta. Later in pregnancy, higher oxygen concentrations are required to
      support the rapid growth of the fetus. This transition, which appears unique to
      the human placenta, must be negotiated safely for a successful pregnancy.
      Normally, onset of the maternal placental circulation is a progressive periphery
      centre phenomenon, and is associated with extensive villous regression to form
      the chorion laeve. In cases of miscarriage, onset of the circulation is both
      precocious and disorganized, and excessive placental oxidative stress and villous
      regression undoubtedly contribute to loss of the pregnancy. Comparison of
      experimental and in vivo data indicates that fluctuations in placental oxygen
      concentration are a more powerful stimulus for the generation of oxidative stress
      than chronic hypoxia alone. Placental oxidative and endoplasmic reticulum stress
      appear to play key roles in the pathophysiology of complications of pregnancy,
      such as intrauterine growth restriction and preeclampsia, through their adverse
      impacts on placental function and growth. Establishing an inviolable maternal
      blood supply for the second and third trimesters is therefore one of the most
      crucial aspects of human placentation.

PMID- 19175806
TI  - Research review: crossing syndrome boundaries in the search for brain
      endophenotypes.
AB  - The inherent imprecision of behavioral phenotyping is the single most important
      factor contributing to the failure to discover the biological factors that are
      involved in psychiatric and neurodevelopmental disorders (e.g., Bearden &
      Freimer, 2006). In this review article we argue that in addition to an
      appreciation of the inherent complexity at the biological level, a rather urgent
      task facing behavioral scientists involves a reconsideration of the role that
      clinical syndromes play in psychological theorizing, as well as in research into
      the biological basis of cognition and personality. Syndrome heterogeneity, cross
      syndrome similarities and syndrome comorbidities question the relevance of
      syndromes to biological research. It is suggested that the search for brain
      endophenotypes, intermediate between genes and behavior, should be based on cross
      syndrome, trait classification. Cohort selection should rest on behavioral
      homogeneity, enabling, when necessary, syndrome heterogeneity.

PMID- 19175805
TI  - Nutritional programming of disease: unravelling the mechanism.
AB  - Nutritional programming is the process through which variation in the quality or
      quantity of nutrients consumed during pregnancy exerts permanent effects upon the
      developing fetus. Programming of fetal development is considered to be an
      important risk factor for non-communicable diseases of adulthood, including
      coronary heart disease and other disorders related to insulin resistance. The
      study of programming in relation to disease processes has been advanced by
      development of animal models, which have utilized restriction or over-feeding of
      specific nutrients in either rodents or sheep. These consistently demonstrate the
      biological plausibility of the nutritional programming hypothesis and,
      importantly, provide tools with which to examine the mechanisms through which
      programming may occur. Studies of animals subject to undernutrition in utero
      generally exhibit changes in the structure of key organs such as the kidney,
      heart and brain. These appear consistent with remodelling of development,
      associated with disruption of cellular proliferation and differentiation. Whilst
      the causal pathways which extend from this tissue remodelling to disease can be
      easily understood, the processes which lead to this disordered organ development
      are poorly defined. Even minor variation in maternal nutritional status is
      capable of producing important shifts in the fetal environment. It is suggested
      that these environmental changes are associated with altered expression of key
      genes, which are responsible for driving the tissue remodelling response and
      future disease risk. Nutrition-related factors may drive these processes by
      disturbing placental function, including control of materno-fetal endocrine
      exchanges, or the epigenetic regulation of gene expression.

PMID- 19175807
TI  - The Brief Child and Family Phone Interview (BCFPI): 2. Usefulness in screening
      for child and adolescent psychopatholog.
AB  - BACKGROUND: This study examines the use of the Brief Child and Family Phone
      Interview (BCFPI) to screen for childhood psychiatric disorder based on
      Diagnostic Interview Schedule for Children Version IV (DISC-IV) classifications
      of attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder
      (ODD), conduct disorder (CD), separation anxiety (SAD), generalized anxiety (GAD)
      and major depression (MDD). METHODS: Data for analysis come from a sample of 399
      children and adolescents aged 5-17 years old referred to child mental health
      outpatient services in three Ontario cities. Mothers were administered the BCFPI
      on three occasions: baseline, 2 and 13 months; and the DISC-IV on two occasions:
      1 and 12 months. RESULTS: Based on kappa, test-retest reliability for disorders
      classified by the BCFPI exceeded .50 for all conditions except MDD (.45). In
      receiver operating characteristic (ROC) analysis, area-under-the-curve (AUC)
      estimates for BCFPI scale score associations with DISC-IV classifications of
      disorder exceeded .80 for CD, ODD, ADHD and SAD; and were lower for GAD (.76) and
      MDD (.75). In stratified analyses, there were no statistically significant
      differences in AUC estimates for boys versus girls and 5 to 11 versus 12 to 17
      year-olds. CONCLUSIONS: Classifications of childhood disorder derived from the
      BCFPI provided a reasonable approximation to disorders classified by the DISC-IV
      administered by lay interviewers.

PMID- 19175808
TI  - Perception of tone and aspiration contrasts in Chinese children with dyslexia.
AB  - BACKGROUND: Previous research has shown a relationship between speech perception
      and dyslexia in alphabetic writing. In these studies speech perception was
      measured using phonemes, a prominent feature of alphabetic languages. Given the
      primary importance of lexical tone in Chinese language processing, we tested the
      extent to which lexical tone and aspiration, two fundamental dimensions of
      Cantonese speech not represented in writing, would distinguish dyslexic from non
      dyslexic 8-year-old Chinese children. Tone and aspiration were tested in addition
      to other phonological processing skills across groups to determine the importance
      of different aspects of phonological sensitivity in relation to reading
      disability. METHODS: Dyslexic children and age-matched and reading-level controls
      were tested on their categorical perception of minimal pairs contrasting in tone
      and aspiration, phonological awareness, rapid digit naming, and Chinese reading
      abilities. RESULTS: While performing similarly to reading-level controls,
      dyslexic children perceived tone and aspiration contrasts less categorically and
      accurately than age-matched controls. They also performed more poorly than the
      age-matched controls on rapid digit naming and a measure of phonological
      awareness testing children's sensitivity to different grain size units.
      CONCLUSIONS: Dyslexia in non-alphabetic Chinese correlates with the categorical
      organization and accuracy of Cantonese speech perception, along the tone and
      aspiration dimensions. This association with reading is mediated by its
      association with phonological awareness. Therefore, dyslexia is universally at
      least partly a function of basic speech and phonological processes independent of
      whether the speech dimensions in question are coded in writing.

PMID- 19175809
TI  - Behavioural and cognitive phenotypes in idiopathic autism versus autism
      associated with fragile X syndrome.
AB  - BACKGROUND: In order to better understand the underlying biological mechanism/s
      involved in autism, it is important to investigate the cognitive and behavioural
      phenotypes associated with idiopathic autism (autism without a known cause) and
      comorbid autism (autism associated with known genetic/biological disorders such
      as fragile X syndrome). Parental effects associated with each type of autism also
      serve to cast light on the biological underpinnings of autism. METHOD: Forty-nine
      participants with idiopathic autism (AD; Mean age: 11.16; SD: 6.08) and their
      parents (45 mothers; 34 fathers), and 48 participants with fragile X syndrome and
      co-morbid autism (FXS/AD; Mean age: 17.30; SD: 10.22) and their parents (32
      mothers; 30 fathers) were administered the ADOS-G and the age-appropriate
      Wechsler test to ascertain autism and cognitive profiles respectively. RESULTS:
      The AD and FXS/AD groups showed a similar profile on the ADOS domains, with
      slightly higher scores on the Communication domain in the FXS/AD group, after
      adjusting for full-scale IQ. Marked differences between the groups in their
      cognitive abilities were apparent, with the FXS/AD group showing significantly
      lower scores on all subtests except Comprehension. While no parental effects were
      found for the FXS/AD group, a paternal effect was apparent on the combined ADOS
      score for the AD group. Moreover, midparental effects were found in this group
      for full-scale IQ (FSIQ) and verbal IQ (VIQ). Analyses also revealed parental
      effects for the subtests of Similarities, Vocabulary, and Information with
      predominantly maternal effect, and Digit Span with predominantly paternal effect.
      Both parents contributed to the midparental effect for Processing Speed.
      CONCLUSIONS: The results, together with our previous findings, suggest that the
      postulated combination of susceptibility genes for autism may primarily involve
      cognitive rather than behavioural processes.

PMID- 19175811
TI  - How neuropsychology informs our understanding of developmental disorders.
AB  - This review includes 1) an explanation of what neuropsychology is, 2) a brief
      history of how developmental cognitive neuroscience emerged from earlier
      neuropsychological approaches to understanding atypical development, 3) three
      recent examples that illustrate the benefits of this approach, 4) issues and
      challenges this approach must face, and 5) a forecast for the future of this
      approach.

PMID- 19175810
TI  - The past achievements and future promises of developmental psychopathology: the
      coming of age of a discipline.
AB  - Over the past decades, developmental psychopathology has coalesced into a
      discipline that has made significant contributions toward the understanding of
      risk, psychopathology, and resilience in individuals across the life course. The
      overarching goal of the discipline has been to elucidate the interplay among
      biological, psychological, and social-contextual aspects of normal and abnormal
      development. In addition to directing efforts toward bridging fields of study and
      aiding in elucidating important truths about the processes underlying adaptation
      and maladaptation, investigators in developmental psychopathology have been
      equally devoted to developing and evaluating methods for preventing and
      ameliorating maladaptive and psychopathological outcomes. Increasingly, efforts
      are being made to conduct investigations at multiple levels of analysis and to
      translate basic research knowledge into real-world contexts. In this article, the
      contributions, challenges, and future directions of the field are highlighted.

PMID- 19175812
TI  - Personal reflections on observational and experimental research approaches to
      childhood psychopathology.
AB  - The past 50 years have seen dramatic changes in childhood psychopathology
      research. The goal of this overview is to contrast observational and experimental
      research approaches; both have grown more complex such that the boundary between
      these approaches may be blurred. Both are essential. Landmark observational
      studies with long-term follow-up (Robins, 1966; Yarrow, Campbell, & Burton, 1970)
      have had - and continue to have - unique impact on clinical research and
      practice. Epidemiological studies showed high rates of psychological disorder and
      their close tie to neurological impairment (Rutter, Tizard, & Whitemore, 1970).
      These studies have current impact with respect to brain imaging correlates of
      clinical outcome. Pharmacological studies, particularly those on stimulants and
      on treatment of pediatric obsessive compulsive disorder (OCD), have propelled
      experimental methodology and inspired translational approaches. Predicted future
      trends are: more informed subgrouping of our heterogeneous phenotypes, reliance
      on multicenter trials, and documentation of non-conventional methods of care
      delivery.

PMID- 19175813
TI  - The influence of family structure, the TPH2 G-703T and the 5-HTTLPR serotonergic
      genes upon affective problems in children aged 10-14 years.
AB  - BACKGROUND: Both genetic and psychosocial risk factors influence the risk for
      depression in development. While the impacts of family structure and of
      serotonergic polymorphisms upon individual differences for affective problems
      have been investigated separately, they have never been considered together in a
      gene-environment interplay perspective. METHODS: We examined the effects of
      family structure and two serotonergic polymorphisms (the TPH2 G-703T and the 5
      HTTLPR) upon depressive symptoms assessed by the new CBCL/6-18 DSM-oriented
      Affective Problems scale in a general population sample of 607 Italian children
      aged 10-14 years. RESULTS: Belonging to 'one-parent' families, the TPH2 G-703T 'G
      variant', and the 5-HTTLPR 'short' alleles were associated - both alone and in
      apparent gene-by-environment interaction - with higher Affective Problems scores.
      As predicted by quantitative genetics theory, both polymorphisms contributed with
      a small effect size, while 'family structure' had a moderate effect size.
      CONCLUSIONS: A putative hazard factor impinging on individual risk at the family
      wide level, namely family structure, appears to act interactively with two
      pivotal serotonergic genes in heightening risk for Affective Problems. Although
      it remains to be demonstrated that belonging to a one- rather than a two-parent
      family has true environmental causal effects on Affective Problems, these data
      may contribute to identify/prevent risk for depression in childhood.

PMID- 19175814
TI  - Child-therapist alliance and clinical outcomes in cognitive behavioral therapy
      for child anxiety disorders.
AB  - BACKGROUND: Few studies have examined the link between child-therapist alliance
      and outcome in manual-guided cognitive behavioral therapy (CBT) for children
      diagnosed with anxiety disorders. This study sought to clarify the nature and
      strength of this relation. METHODS: The Therapy Process Observational Coding
      System for Child Psychotherapy - Alliance scale (TPOCS-A; McLeod, 2005) was used
      to assess the quality of the child-therapist alliance. Coders independently rated
      123 CBT therapy sessions conducted with 34 children (aged 6-13 years) diagnosed
      with anxiety disorders. Parents reported on children's symptomatology at pre- mid
      , and post-treatment. RESULTS: A stronger child-therapist alliance early in
      treatment predicted greater improvement in parent-reported outcomes at mid
      treatment but not post-treatment. However, improvement in the child-therapist
      alliance over the course of treatment predicted better post-treatment outcomes.
      CONCLUSIONS: The quality of the child-therapist alliance assessed early in
      treatment may be differentially associated with symptom reduction at mid- and
      post-treatment. Results underscore the importance of assessing the relation
      between alliance and outcome over the course of therapy to clarify the role the
      child-therapist alliance plays in child psychotherapy.

PMID- 19175815
TI  - Reduced activation in lateral prefrontal cortex and anterior cingulate during
      attention and cognitive control functions in medication-naive adolescents with
      depression compared to controls.
AB  - BACKGROUND: There is increasing recognition of major depressive disorder (MDD) in
      adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate
      circuitries mediating cognitive control functions have been implicated in the
      pathogenesis and been related to problems with controlling negative thoughts. No
      neuroimaging studies of cognitive control functions, however, exist in paediatric
      depression. This study investigated whether medication-naive adolescents with MDD
      show abnormal brain activation of fronto-striatal and fronto-cingulate networks
      when performing tasks of attentional and cognitive control. METHODS: Event
      related functional magnetic resonance imaging was used to compare brain
      activation between 21 medication-naive adolescents with a first-episode of MDD
      aged 14-17 years and 21 healthy adolescents, matched for handedness, age, sex,
      demographics and IQ. Activation paradigms were tasks of selective attention
      (Simon task), attentional switching (Switch task), and motor response inhibition
      and error detection (Stop task). RESULTS: In all three tasks, adolescents with
      depression compared to healthy controls demonstrated reduced activation in task
      relevant right dorsolateral (DLPFC), inferior prefrontal cortex (IFC) and
      anterior cingulate gyrus (ACG). Additional areas of relatively reduced activation
      were in the parietal lobes during the Stop and Switch tasks, putamen, insula and
      temporal lobes during the Switch task and precuneus during the Simon task.
      CONCLUSIONS: This study shows first evidence that medication-naive adolescents
      with MDD are characterised by abnormal function in ACG and right lateral
      prefrontal cortex during tasks of attention and performance monitoring,
      suggesting an early pathogenesis of these functional abnormalities attributed to
      MDD.

PMID- 19175816
TI  - Differential susceptibility to rearing experience: the case of childcare.
AB  - BACKGROUND: Inconsistencies regarding developmental effects of non-maternal
      childcare may be caused by neglecting the possibility that children are
      differentially susceptible towards such experiences. METHOD: Interactions between
      difficult/negative child temperament and childcare type, quantity, and quality on
      teacher-rated behavior problems and social competence at 54 months and in
      kindergarten were investigated via multiple regression using data from the NICHD
      Study of Early Child Care. RESULTS: Childcare quality interacted with infant
      negativity in predicting behavior problems and social competence, whereas effects
      of quantity and type were independent of child temperament. Consistent with
      Belsky's (1997) differential susceptibility hypothesis, children with difficult
      temperaments as infants exhibited both more behavior problems when faced with low
      quality care and fewer when experiencing high quality care than children with
      easy temperaments. CONCLUSIONS: Negatively-emotional infants appear to be more
      affected by the quality of care they experience - both negatively and positively 
      than other young children.

PMID- 19175817
TI  - Executive function deficits in children with fetal alcohol spectrum disorders
      (FASD) measured using the Cambridge Neuropsychological Tests Automated Battery
      (CANTAB).
AB  - BACKGROUND: Chronic prenatal alcohol exposure causes a spectrum of deleterious
      effects in offspring, collectively termed fetal alcohol spectrum disorders
      (FASD), and deficits in executive function are prevalent in FASD. The goal of
      this research was to test the hypothesis that children with FASD exhibit
      performance deficits in tasks that assess attention, planning and spatial working
      memory. METHODS: Subjects (8-15 years male and female children) with a diagnosis
      of fetal alcohol syndrome (FAS), partial FAS (pFAS), or alcohol-related
      neurodevelopmental disorder (ARND), and age- and sex-matched controls, completed
      four tasks selected from the Cambridge Neuropsychological Tests Automated Battery
      (CANTAB). RESULTS: Compared with age-matched control children (n = 92), subjects
      with FASD (n = 89) exhibited longer reaction and decision times (effect size
      range; Cohen's d = .51 to .73), suggesting deficits in attention. Children with
      FASD demonstrated deficits in planning and spatial working memory that became
      more pronounced when task difficulty increased. The largest effect size in this
      study population (Cohen's d = 1.1) occurred in the spatial working memory task.
      Only one outcome measure revealed differences across the diagnostic subgroups,
      although all groups were different from control. CONCLUSION: This study
      demonstrates that deficits in multiple executive function domains, including set
      shifting, planning and strategy use, attention and spatial working memory, can be
      assessed in children with FASD using an easy to administer, brief battery of
      computer-based neuropsychological tasks. The tasks appear to be equally sensitive
      for brain injury resulting from prenatal exposure to alcohol, regardless of the
      presence of facial dysmorphology.

PMID- 19175818
TI  - Nosology and measurement in child and adolescent psychiatry.
AB  - The last 50 years have witnessed enormous strides in the measurement and
      classification of child and adolescent psychiatric disorders. Debates about
      whether we should continue to depend upon a categorical nosology still continue,
      but we argue that, despite the absence of clear dividing lines between
      psychiatric disorders and normality and ubiquity of diagnostic comorbidity, the
      current official approach to nosology has served child and adolescent psychiatric
      research surprisingly well. In particular we point to the utility of non
      developmental diagnostic criteria as tools for discovering developmental effects
      on psychopathology. We also maintain that the search for sharper boundaries
      between disorders is fundamentally mistaken. However, official nosologies have
      tended to privilege information collected in diagnostic interviews and to
      sideline observational and other methods that cannot easily be made to conform to
      the format of their criteria. We suggest that it is time to remedy this
      situation. The ICD-10 and DSM-IV are useless for children under the age of about
      two, while alternatives, such as the DC:0-3, suffer from a profound lack of
      empirical support. We suggest a way forward through the integration of methods
      from temperament and psychopathology research. Finally, we deplore the failure of
      standardized assessment techniques to have penetrated more deeply into everyday
      clinical assessment.

PMID- 19175819
TI  - Early parental depression and child language development.
AB  - OBJECTIVE: To examine the effects of early maternal and paternal depression on
      child expressive language at age 24 months and the role that parent-to-child
      reading may play in this pathway. PARTICIPANTS AND METHODS: The 9-month and 24
      month waves from a national prospective study of children and their families, the
      Early Childhood Longitudinal Study - Birth Cohort (ECLS-B), provided data on
      4,109 two-parent families. Depressive symptoms were measured with a short form of
      the Center for Epidemiologic Studies Depression Scale (CES-D). Parents reported
      on positive parent-infant interactions, child expressive vocabulary, and
      demographic and health information at child age 9 and 24 months. Linear
      regression was used to estimate associations between depression, parenting, and
      child vocabulary. Structural equation modeling was used to test the hypothesis
      that parent reading behavior mediates the parent depression to child vocabulary
      pathway. These models were adjusted for demographic indicators. RESULTS: As
      previously reported from this national sample, 14% of mothers and 10% of fathers
      exhibited elevated levels of depressive symptoms at 9 months. For both mothers
      and fathers, depression at 9 months was negatively associated with
      contemporaneous parent-to-child reading. Only for fathers, however, was earlier
      depression associated with later reading to child and related child expressive
      vocabulary development. A model describing this pathway demonstrated a
      significant indirect pathway from depression to vocabulary via parent reading to
      child. CONCLUSIONS: Depression is a significant problem among both mothers and
      fathers of young children, but has a more marked impact on the father's reading
      to his child and, subsequently, the child's language development.

PMID- 19175820
TI  - One-year incidence of psychiatric disorders and associated risk factors among
      adolescents in the community.
AB  - BACKGROUND: We have few data on incidence of psychiatric disorders among
      adolescents. This study examined first incidence of disorders among adolescents
      and baseline factors which increased or decreased risk of new onset cases a year
      later. METHODS: Data were analyzed from Teen Health 2000 (TH2K), a probability
      sample of 4,175 youths 11-17 and their parents assessed at baseline and 3,134 of
      these youth-parent dyads followed up a year later. Disorders examined were
      anxiety, mood, attention deficit hyperactivity disorder (ADHD), disruptive, and
      substance abuse/dependence disorders in the past year. Risk and protective
      factors were assessed from three domains: status factors, personal and social
      resources, and stressors. Logistic regression models were used to estimate odds
      of incident disorders for each risk and protective factor. RESULTS: Incidence
      rates were 2.8% for anxiety, 1.5% for mood, 1.2% for ADHD, 2.5% for disruptive,
      2.9% for substance abuse/dependence, and 7.5% for one or more DSM-IV disorders.
      Multivariate analyses identified few independent predictors of incidence. The
      most consistent factors across disorders involved indicators of stress. The role
      of adverse family context was particularly noteworthy, predicting incidence of
      every disorder examined. Personal resources such as mastery consistently enhanced
      resilience to onset of first episodes. The presence of multiple risk factors,
      cumulative burden, substantially increased risk of first incidence of all
      disorders examined. CONCLUSIONS: The incidence of any disorder of 7.5% was
      similar to two earlier studies using DSM-III-R criteria (8.9 and 10.6,
      respectively). This is the first study to estimate incidence of DSM-IV disorders
      for a range of diagnostic categories, and with the exception of substance use
      disorders, the rates are quite different from one earlier study using DSM-II-R
      criteria. A clear pattern emerged from the analyses. That is, psychiatric
      disorders, like other chronic diseases, are the product of multiple factors and
      these factors in turn have effects on multiple disorders.

PMID- 19175821
TI  - Cognitive and emotional associations to positive schizotypy during adolescence.
AB  - BACKGROUND: Sub-clinical symptoms of psychosis such as hallucinations and
      delusions, known as positive schizotypy, constitute one of the strongest
      predictive factors for adult psychotic disorders. Recent cognitive models suggest
      that the expression of positive schizotypy is associated with depression,
      anxiety, metacognitive beliefs and self-monitoring deficits. In this study, we
      present empirical data on the relationships positive schizotypy hold with both
      emotional and cognitive factors. METHODS: A sample of 163 adolescents (77
      females) participated in this study (mean age 15.3, 12-18 years). Subjects filled
      out self-report questionnaires assessing the emotional dimensions of depression
      and anxiety, as well as metacognitive beliefs. Self-monitoring skills were
      assessed using an action monitoring paradigm sensitive to dysfunctions associated
      with psychosis-proneness. Multivariate regression models were employed to examine
      emotional and cognitive contributions to positive schizotypy during adolescence.
      RESULTS: Analyses revealed that dimensions of depression, anxiety, and
      metacognitive beliefs significantly correlated with the expression of positive
      schizotypy. When accounting for the effects of depression and metacognitive
      beliefs in adolescents reporting hallucinations, self-monitoring dysfunctions
      seemed to represent a significant factor in the expression of positive
      schizotypy. CONCLUSION: The present results suggest that the expression of
      positive schizotypy during adolescence is modulated by emotional factors of
      depression and anxiety, as well as metacognitive beliefs and self-monitoring
      dysfunctions. The current data lend some evidence that supports the cognitive
      developmental account of positive symptom formation before the onset of a
      psychotic disorder.

PMID- 19175822
TI  - Chinese female nurses' perceptions of male genitalia-related care--Part 1.
AB  - AIMS: To explore Chinese female nurses' experiences of male genitalia-related
      care. BACKGROUND: Male patients who require male genitalia-related care may have
      psychosocial and sexual concerns and needs. Nurses' attitudes and conduct in the
      provision of male genitalia-related care, if negative, may obviate meeting these
      needs. Previous research indicates that limited studies have been conducted
      focusing on nurses' perceptions, responses and attitudes towards male genitalia
      related care. There is a dearth of knowledge about the practice of Chinese female
      nurses delivering male genitalia-related care, particularly given that physical
      contact between Chinese adults of different genders outside marriage is
      traditionally prohibited. DESIGN: This study is an exploratory qualitative study.
      METHODS: Through purposive sampling, eight subjects were approached and semi
      structured interviews were conducted. Digitally recorded interviews were
      transcribed verbatim and thematic analysis was conducted. The strategies of long
      engagement, member checking, peer debriefing and journal writing were used to
      establish trustworthiness. RESULTS: Two themes emerged from interviews:
      'association with sexuality' and 'consequences'. The theme 'association with
      sexuality' comprised the sub-themes of 'being sexual', 'impact on intimate
      relationship' and 'emotional responses'. The theme 'consequences' was constituted
      by the sub-themes of 'care with preconditions', 'unavoidable responsibilities'
      and 'limited involvement with implicit approval'. CONCLUSIONS: This study
      suggests that Chinese female nurses' perceptions, responses and attitudes towards
      male genitalia-related care may be negative, with the consequence that the
      quality of male genitalia-related care might be compromised. The Chinese culture
      of sexual conservativeness may play a critical role. RELEVANCE TO CLINICAL
      PRACTICE: Risks may be embedded in the practice of male genitalia-related care by
      Chinese female nurses. Particular attention, therefore, should be drawn to the
      possibility of adverse effects of Chinese female nurses delivering male genitalia
      related care on them and their patients.

PMID- 19175823
TI  - Attitudes toward dementia-related aggression among staff in Japanese aged care
      settings.
AB  - AIM AND OBJECTIVE: This study investigated attitudes of Japanese aged care staff
      toward aggression by people with dementia. Relationships between staff attitudes,
      professional characteristics and clinical practice were explored. BACKGROUND:
      Aggressive behaviour is often demonstrated by people with dementia and may be
      influenced by many factors including an inability by the individual to
      appropriately express their needs, difficulties with assessment, as well as
      organisational and practice issues. DESIGN: Survey. METHOD: Twenty-seven
      facilities/organisations located in the western and middle parts of Japan were
      surveyed. Staff (n = 675) employed in these facilities provided personal and
      professional information and completed the Attitudes Towards Aggression Scale.
      RESULTS: Staff who were older, had more clinical experience, higher education
      and/or a higher position reported more positive attitudes towards patient
      aggression. Staff with negative attitudes towards patients who are aggressive
      reported using chemical and/or physical restraint more often than staff with
      positive attitudes. CONCLUSIONS: Dementia education as well as restraint policy
      will be useful in addressing negative staff attitudes, in particular it may help
      to reverse the myth that restraint is necessary for staff protection.
      Furthermore, staff counseling may help to reduce stressors and to change staff
      negative attitudes towards people with dementia who display aggression. RELEVANCE
      TO CLINICAL PRACTICE: The findings show that negative staff attitudes may
      adversely affect clinical decision making and patient care. Measuring attitudes
      can identify areas requiring education or skill development and enable changes in
      attitudes to be monitored over time.

PMID- 19175824
TI  - A training package for primary care nurses in conducting medication reviews:
      their views and the resultant outputs.
AB  - AIMS: To ascertain nurses' views about training in and undertaking of medication
      reviews and to analyse documented pharmaceutical care issues (PCI) and outputs
      from nurse reviews. BACKGROUND: Primary-care nurses in the UK are increasingly
      expected to contribute effectively to chronic disease management for example by
      undertaking medication reviews. There are concerns that nurse education is
      inadequate for these new roles. Little research is published about nurse
      medication reviews. A pilot study in one Scottish medical practice demonstrated
      that, after training in systematic medication review, practice-based nurses could
      identify medication-related problems. The training, consisting of reading
      material, including self-assessment questions and a training event, was
      subsequently offered to all practice-based nurses in the Community Health
      Partnership (CHP); participants then undertook six reviews to achieve CHP
      accreditation. DESIGN: Survey of participant nurses and analysis of completed
      documentation from reviews. METHODS: A self-completion, postal questionnaire
      distributed three months post-training. Analysis of documentation from reviews
      for PCI and outputs. RESULTS: Eighty-one nurses were offered training: 64 (79%)
      participated; 38 (59%) returned questionnaires. Low confidence levels before
      training (0, very confident; 6, 16% confident) rose afterwards (8, 21% very
      confident; 19, 50% confident). Thirty-two (84%) nurses indicated the training had
      completely or mostly met their needs. A total of 120 nurse reviews were analysed
      and 188 PCI documented, mean 1.6/patient, with 117 outputs, mean 1.0/patient.
      Twenty-seven outputs (23%) involved prescribed medicine changes. CONCLUSIONS: A
      pharmacist-supported training package in medication reviews for primary-care
      nurses is feasible and generally welcome. The training met the needs of most
      respondents although concerns were expressed regarding time pressures and
      knowledge base for extended roles. RELEVANCE TO CLINICAL PRACTICE: Medication
      reviews are vitally important for both patients and the NHS; this approach may be
      useful for nurse prescribers and non-prescribers alike although concerns
      expressed will require attention.

PMID- 19175825
TI  - Palliative chemotherapy for patients with recurrent hepatocellular carcinoma
      after liver transplantation.
AB  - BACKGROUND AND AIM: The majority of patients with post-transplantation recurrence
      of hepatocellular carcinoma (HCC) have extrahepatic metastases and multifocal
      lesions. Therefore, they have few treatment options and may not be amenable for
      local therapy. The safety and efficacy of palliative chemotherapy in this
      population has not been reported. METHODS: We retrospectively analyzed 24
      patients who received palliative chemotherapy for recurrent HCC after liver
      transplantation between January 2000 and December 2006 at the Seoul National
      University Hospital. RESULTS: The mean age of patients was 55 years (range 42-70
      years). The most commonly used chemotherapeutic regimens were 5-fluorouracil (5
      FU)/cisplatin (n = 9), which was followed by capecitabine/cisplatin (n = 4), 5
      FU/mitomycin (n = 3), 5-FU/oxaliplatin (n = 1), S-1 (n = 1), capecitabine (n =
      1), gemcitabine/oxaliplatin (n = 1), gemcitabine/cisplatin (n = 1), 5
      FU/interferon (n = 1) and sorafenib (n = 2). The Grade 3/4 hematological toxicity
      was neutropenia (29.1%), thrombocytopenia (20.9%) and anemia (20.9%). There were
      no cases of neutropenic fever or bleeding events. The Grade 3/4 non-hematological
      toxicity included elevation of liver transaminase (8.4%) and jaundice (16.7%). No
      patient showed an objective response and four patients (16.7%) demonstrated
      stable disease. The median time to progression was 7.0 weeks (95% CI 5.8-8.2) and
      the median overall survival was 16.6 weeks (95% CI 10.1-23.1). CONCLUSION:
      Palliative chemotherapy can be delivered to patients with recurrent HCC after
      liver transplantation with tolerable toxicity. However, the efficacy to date is
      not satisfactory. Therefore, more effective systemic chemotherapy is needed for
      this group of patients.

PMID- 19175826
TI  - STAT3 expression in gastric cancer indicates a poor prognosis.
AB  - BACKGROUND AND AIM: Signal transducers and activators of transcription (STAT)
      behave as signal transducers in the cytoplasm and as transcription factors in the
      nucleus. In the current study, we analyzed the immunohistochemical staining
      patterns of gastrectomy tissue specimens. We investigated the expression of STAT3
      and STAT5 and estimated the relationship between STAT and cancer prognosis.
      METHODS: One hundred patients who underwent gastrectomy due to gastric
      adenocarcinoma at Bundang CHA hospital between January 2000 and May 2005 were
      studied. Immunohistochemistry was carried out using antibodies against STAT3 and
      STAT5. The interpretation of the immunohistochemical staining was based on the
      proportion of stained cells in the field: positive, > 10% stained cells; and
      negative, < 10% stained cells. RESULTS: The longest diameter of tumor was 4.67 cm
      in the positive group and 3.76 cm in the negative group, and these results were
      not statistically different (P-value = 0.112). Higher T (primary tumor) value (P
      value = 0.05), more regional lymph node invasion (P-value = 0.008) and higher TNM
      staging (P-value = 0.069) were significantly related to STAT3 positivity, but
      Helicobacter pylori infection or atrophic gastritis were not related. A lower
      survival rate was observed in the STAT3-positive group (P-value = 0.001). The
      results of STAT5 were not statistically different with respect to TNM staging and
      survival (P-value = 0.958). We thus report that the immunohistochemical results
      of STAT3 revealed a significant association with TNM staging and survival.
      CONCLUSION: We anticipate that STAT3 may be used as a molecular staging biomarker
      predicting poor prognosis of gastric cancer.

PMID- 19175827
TI  - Unclassified mucin phenotype of gastric adenocarcinoma exhibits the highest
      invasiveness.
AB  - BACKGROUND AND AIM: Gastric cancers present with distinctive carcinogenesis
      pathways that vary with the mucin phenotypes. We attempted to elucidate the
      relations between the characteristics of the mucin phenotypes of gastric cancer
      and the tumor invasiveness. METHODS: Gastric adenocarcinomas that were resected
      surgically between August 2005 and April 2007 were included in the present study.
      The gastric cancers were subclassified into gastric and intestinal mucin
      phenotypes if more than 10% of cancer cells exhibited gastric (MUC5AC and/or
      MUC6) and intestinal (MUC2 or CD10) markers, respectively. RESULTS: The mucin
      phenotypes of 123 gastric cancers were gastric (n = 31), intestinal (n = 43),
      mixed (n = 28) and unclassified (n = 21). The mucin phenotype was related to
      histological type (P < 0.001), Lauren's classification (P = 0.001) and size (P =
      0.014) of the gastric adenocarcinoma, but not to its location or to the presence
      of Helicobacter pylori infection. The unclassified mucin phenotype exhibited the
      largest number of lymph node metastases (P = 0.007), lymphatic invasions (P <
      0.001) and neural invasions (P = 0.026), whereas the intestinal mucin phenotype
      exhibited the lowest invasiveness. CONCLUSION: The mucin phenotype reflects the
      biological behavior of gastric cancer, with the intestinal and unclassified mucin
      phenotypes exhibiting the lowest and highest invasiveness, respectively.

PMID- 19175828
TI  - SRD5B1 gene analysis needed for the accurate diagnosis of primary 3-oxo-Delta4
      steroid 5beta-reductase deficiency.
AB  - BACKGROUND AND AIM: We encounter hyper-3-oxo-Delta(4) bile aciduria in patients
      with severe cholestatic liver disease or fulminant liver failure during the
      neonatal period. However, simply by bile acid analysis, it is difficult to
      distinguish hyper-3-oxo-Delta(4) bile aciduria from primary 3-oxo-Delta(4)
      steroid 5beta-reductase deficiency. METHODS: To determine whether 3-oxo-Delta(4)
      steroid 5beta-reductase (SRD5B1) gene analysis is required for the accurate
      diagnosis of 3-oxo-Delta(4)-steroid 5beta-reductase deficiency, we evaluated the
      laboratory data, bile acid analysis and SRD5B1 gene analysis from six patients
      with hyper-3-oxo-Delta(4) bile aciduria. RESULTS: Based upon the results, four
      patients who had developed neonatal liver failure were diagnosed as having
      neonatal hemochromatosis. Two patients with chronic cholestasis were diagnosed as
      having primary 3-oxo-Delta(4)-steroid 5beta-reductase deficiency by SRD5B1 gene
      analysis. The SRD5B1 gene in these two patients had a heterozygous mutation,
      G737A (Gly 223 Glu) in one patient and C217T (Arg 50 stop) in the other.
      CONCLUSIONS: Based upon our limited data, we conclude that SDR5B1 gene analysis
      is required for the accurate diagnosis of 3-oxo-Delta(4)-steroid 5beta-reductase
      deficiency. Moreover, we think that it is important to elucidate whether there is
      a heterozygous or a compound heterozygous mutation of the SRD5B1 gene in our two
      patients.

PMID- 19175829
TI  - Expression of intercellular adhesion molecule (ICAM)-1 or ICAM-2 is critical in
      determining sensitivity of pancreatic cancer cells to cytolysis by human
      gammadelta-T cells: implications in the design of gammadelta-T-cell-based
      immunotherapies for pancreatic cancer.
AB  - BACKGROUND AND AIMS: gammadelta-T cells can recognize and kill malignant cells,
      particularly those of epithelial origin, through mechanisms which do not require
      the recognition of tumor-specific antigens (innate immune response). This natural
      ability of gammadelta-T cells to kill tumor cells in a tumor antigen-independent
      manner provides a strong rationale for developing clinical trials designed to
      exploit the innate antitumor properties of gammadelta-T cells. METHODS: In vitro
      studies were carried out to asses the sensitivity of pancreatic cancer cells (MIA
      PaCa2, BxPC-3, PANC-1) to killing by ex vivo expanded human gammadelta-T cells.
      RESULTS: The capacity of gammadelta-T cells to bind to as well as to kill
      pancreatic cancer cells correlated with the degree of surface expression of key
      intercellular adhesion molecules (ICAM) present on pancreatic cancer cells.
      Moreover, pancreatic cancer cells expressing neither ICAM-1 nor ICAM-2 were bound
      poorly by gammadelta-T cells and were found to be resistant to gammadelta-T-cell
      killing. However, upon transfection of resistant cells with ICAM-1 or ICAM-2,
      gammadelta-T cells were then able to bind to and subsequently kill these cells.
      CONCLUSION: In vitro, the expression of ICAM-1 or ICAM-2 on human pancreatic
      cancer cells is critically important in determining the extent to which these
      cells are sensitive to killing by human gammadelta-T cells. Accordingly, in
      ongoing and future clinical studies using gammadelta-T cells for the treatment of
      a variety of epithelial-derived solid tumors-including pancreatic cancer
      interventions intended to modulate ICAM expression on tumor cells may become
      important adjuncts to gammadelta-T-cell-based immunotherapies.

PMID- 19175830
TI  - Effects of combination treatment with famotidine and methylmethionine sulfonium
      chloride on the mucus barrier of rat gastric mucosa.
AB  - BACKGROUND AND AIM: In Japan, peptic ulcer disease (PUD) is treated clinically
      with a combination of a mucosal protectant and acid suppressants, but there is
      scant information regarding the effects of these drugs on normal gastric mucus
      cells. In the present study, the effects of co-administration of methylmethionine
      sulfonium chloride (MMSC) and famotidine on rat gastric mucus cells were
      investigated using both biochemical and histological methods. METHODS: Rats were
      divided into four groups: controls were given carboxymethylcellulose orally once
      daily for 7 days and the second, third and fourth groups were treated similarly
      with famotidine (famotidine group), MMSC (MMSC group) or famotidine plus MMSC
      (combination group). After killing the rats on the 8th day, the stomachs were
      removed and the biosynthesis and amount of mucin in different areas of the
      gastric mucosa were compared among groups. Using anti-mucin monoclonal
      antibodies, the mucin content and immunoreactivity were also compared. RESULTS:
      Both the biosynthesis and accumulation of mucin were significantly decreased in
      the famotidine group, but increased in the MMSC and combination groups. The
      amount and immunoreactivity of surface mucus cell-derived mucin were both reduced
      in the famotidine group, and increased in the MMSC and combination groups. There
      was no difference among the groups in the content and immunoreactivity of gland
      mucus cell-derived mucin. CONCLUSION: Famotidine-induced suppression of gastric
      surface mucus cell function is prevented by combined treatment with MMSC, raising
      the possibility of a more effective cure of PUD.

PMID- 19175831
TI  - Differential expression of microRNA species in human gastric cancer versus non
      tumorous tissues.
AB  - BACKGROUND AND AIM: MicroRNAs (miRNAs) play important roles in carcinogenesis.
      The global miRNA expression profile of gastric cancer has not been reported. The
      purpose of the present study was to determine the miRNA expression profile of
      gastric cancer. METHODS: Total RNA were first extracted from primary gastric
      cancer tissues and adjacent non-tumorous tissues and then small isolated RNAs (<
      300 nt) were 3'-extended with a poly(A) tail. Hybridization was carried out on a
      microParaflo microfluidic chip (LC Sciences, Houston, TX, USA). After
      hybridization detection by fluorescence labeling using tag-specific Cy3 and Cy5
      dyes, hybridization images were collected using a laser scanner and digitized
      using Array-Pro image analysis software (Media Cybernetics, Silver Spring, MD,
      USA). To validate the results and investigate the biological meaning of
      differential expressed miRNAs, immunohistochemistry was used to detect the
      differential expression of target genes. RESULTS: The most highly expressed
      miRNAs in non-tumorous tissues were miR-768-3p, miR-139-5p, miR-378, miR-31, miR
      195, miR-497 and miR-133b. Three of them, miR-139-5p, miR-497 and miR-768-3p,
      were first found in non-tumorous tissues. The most highly expressed miRNAs in
      gastric cancer tissues were miR-20b, miR-20a, miR-17, miR-106a, miR-18a, miR-21,
      miR-106b, miR-18b, miR-421, miR-340*, miR-19a and miR-658. Among them, miR-340*,
      miR-421 and miR-658 were first found highly expressed in cancer cells. The
      expression of some target genes (such as Rb and PTEN) in cancer tissues was found
      to be decreased. CONCLUSION: To our knowledge, this is the first report about
      these miRNAs associated with gastric cancer. This new information may suggest the
      potential roles of these miRNAs in the diagnosis of gastric cancer.

PMID- 19175832
TI  - Effects of rhubarb on migration of rat hepatic stellate cells.
AB  - BACKGROUND AND AIMS: In chronic liver injury, hepatic stellate cells (HSCs)
      acquire an activated phenotype, migrate to the injured region in response to
      chemotactic factors, and produce extracellular matrix proteins including
      collagen. In this study, we investigated the effects of rhubarb (Rheum palmatum
      L.) on transforming growth factor (TGF)-beta1-induced expressions of alpha-smooth
      muscle actin (SMA) and collagen, and the migration of HSCs. METHODS: HSC-T6, a
      cell line of rat HSCs, was used in the in vitro experiments. An enzyme-linked
      immunosorbent assay and Sircol red assay were used to detect the expressions of
      alpha-SMA and collagen, respectively. HSC-T6 migration was assayed with a
      transwell apparatus. Phosphorylations of Smad2/3 and mitogen-activated protein
      kinases (MAPKs), including extracellular signal-regulated kinase (ERK) 1/2, p38,
      and c-jun N-terminal kinase (JNK), were analyzed with Western blotting. Matrix
      metalloproteinase (MMP)-2 activity was examined by gelatin zymography. RESULTS:
      The results revealed that a rhubarb extract concentration-dependently attenuated
      TGF-beta1-induced alpha-SMA and collagen expressions and migration of HSCs. The
      inhibitory effect of rhubarb was associated with (i) down-regulation of the
      phosphorylation of Smad2/3 and JNK, and (ii) attenuation of MMP-2 activity.
      Within the working concentrations used, the rhubarb extract did not affect cell
      viability of HSCs. CONCLUSION: The results suggest that rhubarb attenuated TGF
      beta1-mediated migration of HSCs possibly by interfering with Smad2/3
      phosphorylation, the MAPK pathway, and MMP-2 activity.

PMID- 19175833
TI  - Cross-species hybridization of woodchuck hepatitis viral infection-induced
      woodchuck hepatocellular carcinoma using human, rat and mouse oligonucleotide
      microarrays.
AB  - BACKGROUND AND AIM: We aimed to evaluate the transcriptional characteristics of
      viral infection-induced woodchuck hepatocellular carcinoma (HCC), to compare the
      use of human, rat and mouse gene arrays for cross-species hybridization, and to
      look into gene expression profiles in woodchuck HCC by the combined use of these
      arrays. METHODS: Commercially available human, rat and mouse oligonucleotide
      microarrays were used to determine the gene expression profiles on the same
      woodchuck liver samples. Differentially expressed genes between HCC and the
      surrounding hepatic tissues found in the arrays were selected for quantitative
      reverse transcription polymerase chain reaction. RESULTS: Despite the difference
      in the number of the probes from each array, the percentage of genes that were
      detectable was similar. Stringent microarray data analysis using both supervised
      and unsupervised methods identified 281 differentially expressed genes via the
      human array with a false discovery rate (FDR) of 0.99%, 107 genes via the rat
      array with an FDR of 1.85% and 78 genes via the mouse array with an FDR of 7.41%.
      Eleven genes were differentially changed in all three arrays that include the
      upregulation of NPM1, H2AFZ, EEF1G, HNRPAB, RPS18, EIF5, CKS2, ARIH1, RPS12 and
      RPS10, and the downregulation of EGR1. The quantitative reverse transcription
      polymerase chain reaction with woodchuck-specific primers confirmed the
      reliability of the microarray results. CONCLUSION: This study further
      demonstrated the utility of cross-species hybridization of microarrays on
      woodchuck HCC. A combined use of three types of arrays identified more
      differential genes in HCC than individual arrays with the human array providing
      the richest information among the three arrays used.

PMID- 19175834
TI  - Predictors and survival in hepatitis B-related hepatocellular carcinoma in New
      South Wales, Australia.
AB  - BACKGROUND AND AIM: Incidence and mortality of hepatocellular carcinoma (HCC) has
      increased markedly over the last three decades in Australia. An increasing
      proportion of HCC cases is related to chronic viral hepatitis including hepatitis
      B virus (HBV) infection. However, there is very limited data on HBV-related HCC
      survival. METHODS: Data on HBV-related HCC cases was obtained from a community
      based linkage study. HCC cases notified to the New South Wales (NSW) Central
      Cancer Registry (CCR) during the period 1994-2002 were linked to HBV
      notifications from the NSW Health Department. Age, sex, country of birth, year of
      diagnosis, tumor stage were extracted from the CCR database. Survival analysis
      was conducted to determine median survival and identify predictors of survival.
      RESULTS: Over the 9-year study period, 278 HCC cases were linked to chronic HBV
      infection. The majority of cases were male (83.5%) and overseas-born (93.6%);
      Asian-born cases accounted for 72.1%. Median survival following HCC diagnosis was
      15.0 months. HCC survival was poorer among older age groups (P < 0.0001), and
      among cases with regional spread (hazard ratio, 3.23; 95% confidence interval,
      1.83-5.69; P < 0.0001) and distant metastases (hazard ratio, 3.85; 95% confidence
      interval, 2.44-6.08; P < 0.0001). Sex, region of birth and study period (1994
      1997 vs 1998-2002) were not associated with HCC survival. CONCLUSION: The vast
      majority of HBV-related HCC were overseas-born, however, region of birth was
      unrelated to HCC survival. The continued extremely poor HCC survival, including
      lack of improvement in HCC survival in more recent years, suggests low uptake of
      HCC screening programs. Public health strategies including early diagnosis and
      appropriate referral for antiviral therapy assessment and increased HCC screening
      among high-risk populations are required to reduce HCC incidence and improve HCC
      survival.

PMID- 19175835
TI  - Treatment of cardiac tamponade during electrophysiology procedures: do
      electrophysiologists need more than drainage?

PMID- 19175836
TI  - Chronaxie of defibrillation: a pathway toward further optimization of
      defibrillation waveform?

PMID- 19175837
TI  - Paradoxical slowing of orthodromic reciprocating tachycardia with loss of bundle
      branch block ipsilateral to the accessory pathway.

PMID- 19175838
TI  - Type II bidirectional ventricular tachycardia as a mechanism of termination of
      sustained ventricular tachycardia.

PMID- 19175839
TI  - Malignant ventricular arrhythmia in a case of adult onset of spinal muscular
      atrophy (Kugelberg-Welander disease).
AB  - We present a case of a 43-year-old male patient with adult onset of spinal
      muscular atrophy (SMA). The patient first came to our attention with
      atrioventricular (AV) block. A dual-chamber pacemaker (DDD-PM) was implanted.
      Four years later, the PM data log showed occurrence of frequent episodes of
      nonsustained ventricular tachycardia (NSVT). The episodes progressed in duration
      and frequency. An electrophysiological study revealed prolonged His-ventricular
      (HV) interval duration and induction of sustained ventricular tachycardia. The
      patient was successfully upgraded to a prophylactic dual-chamber cardioverter
      defibrillator. Our case is the first description of a patient with adult-onset
      SMA (Kugelberg-Welander disease [KWD]) and malignant ventricular arrhythmias.

PMID- 19175840
TI  - Enhanced predictive power of quantitative TWA during routine exercise testing in
      the Finnish Cardiovascular Study.
AB  - INTRODUCTION: We examined whether quantification of T-wave alternans (TWA)
      enhances this parameter's capacity to evaluate the risk for total and
      cardiovascular mortality and sudden cardiac death (SCD). METHODS AND RESULTS: The
      Finnish Cardiovascular Study (FINCAVAS) enrolled consecutive patients (n = 2,119;
      1,342 men and 777 women) with a clinically indicated exercise test with bicycle
      ergometer. TWA (time domain-modified moving average method) was analyzed from
      precordial leads, and the results were grouped in increments of 10 microV. Hazard
      ratios (HR) for total and cardiovascular mortality and SCD were estimated for
      preexercise, routine exercise, and postexercise stages. Cox regression analysis
      was performed. During follow-up of 47.1 +/- 12.9 months (mean +/- standard
      deviation [SD]), 126 patients died: 62 were cardiovascular deaths, and 33 of
      these deaths were sudden. During preexercise, TWA >or= 20 microV predicted the
      risk for total and cardiovascular mortality (maximum HR >4.4 at 60 microV, P <
      0.02 for both). During exercise, HRs of total and cardiovascular mortality were
      significant when TWA measured >or=50 microV, with 90 microV TWA yielding maximum
      HRs for total and cardiovascular death of 3.1 (P = 0.03) and 6.4 (P = 0.002),
      respectively. During postexercise, TWA >or=60 microV indicated risk for total and
      cardiovascular mortality, with maximum HR of 3.4 at 70 microV (P = 0.01) for
      cardiovascular mortality. SCD was strongly predicted by TWA levels >or=60 microV
      during exercise, with maximum HR of 4.6 at 60 microV (P = 0.002), but was not
      predicted during pre- or postexercise. CONCLUSION: Quantification of TWA enhances
      its capacity for determination of the risk for total and cardiovascular mortality
      and SCD in low-risk populations. Its prognostic power is superior during exercise
      compared to preexercise or postexercise.

PMID- 19175841
TI  - Single-catheter technique for pulmonary vein antrum isolation: is it sufficient
      to identify and close the residual gaps without a circular mapping catheter?
AB  - OBJECTIVES: The present study was designed to investigate the feasibility and
      efficacy of single ablation catheter for complete circumferential pulmonary vein
      antrum (PVA) isolation. BACKGROUND: Complete isolation of pulmonary veins is the
      mainstay for atrial fibrillation (AF) ablation. This is usually performed under
      the guidance of a circular catheter. METHODS: One hundred and ten consecutive
      patients with paroxysmal AF were prospectively randomized into two groups: single
      catheter approach (group 1) and double-catheter approach (group 2). After
      performing initial circumferential lesions, residual gaps were mapped and closed
      with single ablation catheter in group 1 or guided by a circular mapping catheter
      in group 2 using an electroanatomic mapping system (CARTO XP, Biosense-Webster
      Inc., Diamond Bar, CA, USA). RESULTS: Complete bilateral PVA isolation was
      achieved in 22 of the 110 patients after initial ablation. All residual gaps
      could be correctly identified by activation mapping using single ablation
      catheter. The distribution of these residual gaps was asymmetric. In group 1, 25
      gaps along the right PVA lesions and 49 gaps along the left PVA lesions were
      identified. All the residual gaps were closed with single-catheter approach. In
      group 2, 28 gaps on the right side and 53 gaps on the left side were identified
      using a circular catheter and closed with further ablations. The procedure data
      and clinical outcomes between the two groups were comparable. CONCLUSIONS: Single
      ablation catheter technique is feasible and as effective as circular catheter
      mapping in localizing the residual gaps for PVA isolation during ablation of
      paroxysmal AF.

PMID- 19175842
TI  - The use of a standard radiofrequency energy delivery system to facilitate
      transseptal puncture.
AB  - Transseptal puncture is a standard means of catheter access to the left atrium
      via the venous system, but carries a risk of cardiac perforation. Stretching and
      increased force to traverse the septum are required with elastic, aneurysmal, or
      thickened interatrial tissue. We describe a technique that facilitates
      transseptal puncture by applying brief pulses of radiofrequency energy from a
      standard electrosurgical cautery generator through the needle tip.

PMID- 19175843
TI  - Inappropriate ICD discharges in single-chamber versus dual-chamber devices in the
      pediatric and young adult population.
AB  - BACKGROUND: Implantable cardioverter defibrillator (ICD) use is increasing in
      young patients and is frequently complicated by inappropriate device discharges
      (IDs), leading to discomfort, anxiety and, potentially, proarrhythmia. Dual
      chamber (DC) ICDs may decrease IDs by improving rhythm discrimination, but are
      associated with increased size, expense, and implant complications. We examined
      whether the frequency of IDs was the same in dual- and single-chamber (SC) ICDs
      in young patients. METHODS: A multicenter review of patients <or=30 years of age
      with ICDs was performed. Demographic data and number of appropriate discharges
      (ADs) and IDs were collected. ADs and IDs were categorized after review of the
      episode by the primary electrophysiologist. RESULTS: Of 168 subjects (SC = 52;
      female = 76), 41 patients received 139 ADs, while 35 patients received 159 IDs.
      There were no differences related to gender or primary diagnosis, but patients
      with SC versus DC devices were younger (12.3 +/- 5.0 years vs 14.9 +/- 4.4 years,
      P < 0.0001) at implant. SC and DC devices were implanted with the same frequency
      for primary and secondary prevention. There were no significant differences in
      the incidence of IDs or ADs between the patients with SC or DC devices (AD: 12/52
      SC vs 29/116 DC, P = 0.79; ID 7/52 SC vs 28/116 DC, P = 0.13). CONCLUSION: In
      this cohort of young patients, DC ICDs did not provide added protection from IDs.
      Hence, the added complexity and cost of an atrial lead appear unwarranted if used
      solely for assistance with rhythm discrimination in young patients.

PMID- 19175844
TI  - Simpler is better? Full circle in our attempt to decrease cardioverter
      defibrillator inappropriate shocks in the young.

PMID- 19175845
TI  - Radiofrequency catheter ablation with large lesion technologies: what is the
      right formula?

PMID- 19175846
TI  - Does absence (of AF) make the heart grow fonder?

PMID- 19175847
TI  - A potential para-Hisian pacing pitfall.

PMID- 19175848
TI  - Electrophysiologic characteristics of complex fractionated atrial electrograms in
      patients with atrial fibrillation.
AB  - INTRODUCTION: The underlying mechanisms of complex fractionated atrial
      electrogram (CFAE) during radiofrequency catheter ablation (RFCA) of atrial
      fibrillation (AF) have not yet been clearly elucidated. We explored the
      relationships between CFAE and left atrial (LA) voltage, or conduction velocity
      (CV). METHODS AND RESULTS: In 50 patients with AF (23 paroxysmal AF [PAF], 41
      males, mean age 55.76 +/- 10.16 years), the CFAE (average index of fractionation
      of electrograms during AF by interval-analysis algorithm, cycle length [CL]<or=
      120 ms) areas, voltage, and CV were measured at eight different quadrants in each
      patient's LA by analyzing a NavX-guided, color-coded CFAE CL map, a voltage map,
      and an isochronal map (500 ms pacing) generated by contact bipolar electrograms
      (70-100 points in the LA). The results were: (1) CFAE areas were predominantly
      located in the septum, roof, and LA appendage; (2) CFAE area had lower voltage
      than those in non-CFAE area and was surrounded by the areas of high voltage (P <
      0.0001); (3) The CFAE areas had low CVs compared with non-CFAE areas (P < 0.001);
      and (4) The percentage of CFAE area was lower in patients with persistent atrial
      fibrillation (PeAF) compared with those with PAF (P < 0.05). CONCLUSIONS: The
      CFAE area, which is primarily located at the septum, has a low voltage with a
      lower CV, and is surrounded by high-voltage areas. Underlying electroanatomical
      complexity is associated with clustering of CFAEs.

PMID- 19175849
TI  - Presence and duration of atrial fibrillation detected by continuous monitoring:
      crucial implications for the risk of thromboembolic events.
AB  - INTRODUCTION: Asymptomatic atrial fibrillation (AF) can expose patients to the
      risk of stroke. The primary objective of this study was to assess the incidence
      of thromboembolic events in relationship with CHADS(2) (congestive heart failure,
      hypertension, age >or=75 years, diabetes mellitus, and prior stroke, or transient
      ischemic attack) score and AF presence/duration. The secondary objective was to
      compare intermittent versus continuous monitoring strategies. METHODS AND
      RESULTS: Data from patients with an implanted pacemaker and a history of AF were
      analyzed. Thromboembolic risk was quantified through CHADS(2) score. Three AF
      groups were considered: patients with <5-minutes AF on 1 day (AF-free); patients
      with >5-minutes AF on 1 day but <24 hours (AF-5 minutes); patients with AF
      episodes >24 hours (AF-24 hours). Monitoring strategies involving 24-hour Holter,
      1-week Holter, and 30-day Holter were simulated. Data from 568 patients
      continuously monitored for 1 year were analyzed: 171 (30%) had CHADS(2) score =
      0; 269 (47%) had CHADS(2) score = 1; 111 (20%) had CHADS(2) score = 2; and 17
      (3%) had CHADS(2) score >or= 3. During follow-up, 14 patients (2.5%) had an
      ischemic thromboembolic event. AF-24 hours patients numbered 223 (39.2%); AF-5
      minutes, 179 (31.5%); and AF-free, 29.2%. By combining AF presence/duration with
      CHADS(2) score, two subpopulations with markedly different risks of events (0.8%
      vs 5%, P = 0.035) were identified, the former corresponding to AF-free with
      CHADS(2)<or=2, or AF-5 minutes with CHADS(2)<or=1, or AF-24 hours with CHADS(2)=
      0. The mean sensitivity in detecting an AF episode lasting >5 minutes was 44.4%,
      50.4%, and 65.1% for 24-hour Holter, 1-week Holter, and 1-month Holter
      monitoring, respectively. CONCLUSION: In patients with recurrent AF episodes,
      risk stratification for thromboembolic events can be improved by combining
      CHADS(2) score with AF presence/duration.

PMID- 19175850
TI  - A comparison of chronaxies for ventricular fibrillation induction,
      defibrillation, and cardiac stimulation: unexpected findings and their
      implications.
AB  - INTRODUCTION: A low-energy (<or= 4 J) cardioversion shock (LEC) either terminates
      reentrant ventricular tachycardia (VT) or accelerates it to ventricular
      fibrillation (VF). Optimization of the duration and amplitude of LEC shocks could
      improve the success rate of VT termination without VF induction. METHODS AND
      RESULTS: In order to learn how LEC shocks may be optimized, we used an animal
      model to compare the strength-duration curve for VF induction and the strength
      duration curve for cardiac stimulation via the shock coil. Conventional
      implantable cardioverter-defibrillator (ICD) leads were implanted in 12
      narcotized pigs from 20 kg to 25 kg in weight. Stimulation, VF induction, and
      defibrillation pulses were delivered by custom-designed stimulators at preset
      pulse durations and amplitudes. The corresponding hyperbolic strength-duration
      curves were constructed using the least-squares fit method and averaged for all
      the animals. The mean chronaxie for stimulation via the shock coil of 0.23 ms was
      significantly shorter than both defibrillation (4.8 ms) and VF induction (3.1 ms)
      chronaxie values. At a shock duration of 0.3 ms or less, the mean VF-induction
      threshold amplitude exceeded 300 V. CONCLUSION: It may be reasonable to study
      whether LEC pulses from 0.25 ms to 0.30 ms in duration and up to 250 V in
      amplitude would increase therapeutic yield in VT termination without VF induction
      in humans. Contrary to the current belief, the discrepancy between defibrillation
      and stimulation chronaxie is not caused by different electrode size. We postulate
      that the time constant of the fast sodium channel reactivation may be the
      underlying reason.

PMID- 19175851
TI  - Effects of intrapericardial sotalol and flecainide on transmural atrial
      electrophysiology and atrial fibrillation.
AB  - INTRODUCTION: Intrapericardial (IPC) delivery of antiarrhythmic agents is an
      appealing idea to increase the therapeutic width and reduce side effects of
      drugs, particularly in the thin atria. The aim of this study was to determine the
      effects of IPC versus intravenous (IV) d,l-sotalol and flecainide infusion on
      transmural atrial electrophysiology and sustained atrial fibrillation (AF) in the
      goat. METHODS AND RESULTS: Effects of IPC and IV sotalol and flecainide infusion
      on epi- and endocardial atrial electrophysiology, ECG, and tissue drug
      concentrations were studied in goats without and with persistent AF (>24 hours).
      Epicardial atrial refractory period (AERP, bcl 400 ms) increased after 120
      minutes of 1 mg/kg/hour IPC sotalol with 61 +/- 8 ms (P = 0.02), whereas the
      endocardial AERP was not affected. One mg/kg/hour IPC flecainide increased the
      epicardial pacing threshold and the epicardial AERP with 4 +/- 0.5 mA (P = 0.003)
      and 33 +/- 11 ms (P = 0.05), respectively. Endocardial values were unchanged.
      Marked ST-elevations in the precordial ECG leads were observed after IPC
      flecainide. In the AF group, IPC drugs did not prolong AF cycle length to a
      greater extent than IV delivery. The number of cardioversions was not different
      between the two delivery routes. A steep transmural drug concentration gradient
      after IPC sotalol and flecainide was observed in all heart chambers. CONCLUSION:
      IPC sotalol and flecainide infusion in goats markedly affects epicardial atrial
      electrophysiology. IPC delivery, however, does not prolong AFCL or terminate AF
      to a greater extent than IV infusion. This suggests that the perpetuation of AF
      is not dominated by the epicardial and sub epicardial atrial layers.

PMID- 19175852
TI  - Relationship of reverse anatomical remodeling and ventricular arrhythmias after
      cardiac resynchronization.
AB  - INTRODUCTION: Cardiac resynchronization (CRT) affects reverse anatomical
      remodeling in patients with heart failure. CRT has also been associated with
      fewer ventricular arrhythmias and reduced sudden death in some clinical trials,
      but the predictors and mechanism of the antiarrhythmic actions of CRT have not
      been well defined. The purpose of this study is to investigate the relationship
      of reverse anatomical remodeling to ventricular arrhythmias in CRT patients.
      METHODS AND RESULTS: A retrospective analysis was performed of the InSync III
      Marquis study, a prospective, randomized, multicenter CRT trial.
      Echocardiographic data from 198 patients were obtained at baseline and after 6
      months of CRT, and anatomical responders were defined as a reduction in left
      ventricular end systolic volume (LVESV) of >or=15%. Anatomical responders (n =
      71, 36%) demonstrated 29% fewer single premature ventricular contractions beats
      (PVCs) (P = 0.0001), 48% fewer PVC runs (p = 0.0096), and fewer treated episodes
      of ventricular tachycardia or fibrillation (VT/VF) (P = 0.050) than
      nonresponders. Multiple regression analysis demonstrated that responder status
      significantly predicted single PVCs and PVC runs. Gender was the most important
      predictor of treated VT/VF with females having no episodes over 6 months of
      follow-up. CONCLUSIONS: Anatomic responders to CRT demonstrate significantly
      fewer single PVCs and runs of PVCs. The implication of these observations is that
      anatomic remodeling is linked to electrical remodeling.

PMID- 19175853
TI  - DNA damage and apoptosis induced by Pteridium aquilinum aqueous extract in the
      oral cell lines HSG and OSCC-3.
AB  - BACKGROUND: Bracken fern (Pteridium aquilinum) has been consumed by humans and
      animals for centuries. However, its consumption is associated with a high
      incidence of cancer in the upper digestory tract of different species. Although
      the oral cavity is the first site of contact with ingested toxic substances, the
      interaction of bracken fern composites with oral cell lines has not yet been
      studied. METHODS: In order to study the biological responses of oral cells
      exposed to bracken fern, we evaluated the genotoxic and cytotoxic effects of a
      bracken fern aqueous extract in oral cell lines. Human submandibular gland (HSG)
      and human oral epithelium cells (OSCC-3) cells were treated with three different
      concentrations of the extract. DNA damage was determined by the comet assay, and
      cellular morphology was examined by light microscopy. Apoptotic changes were
      evaluated by transmission electron microscopy and TUNEL assay. RESULTS: The comet
      assay revealed that the extract was genotoxic for both cell lines but the results
      were not dose-dependent. The morphological and ultrastructural analyses showed
      that the extract caused conspicuous alterations in both cell types: uncommon
      chromatin condensation, nuclear picnosis, cellular volume decrease, nuclear
      envelope disruption, formation of numerous vacuoles of different sizes and
      apoptotic bodies. The TUNEL assay confirmed apoptosis induction. CONCLUSIONS:
      These results demonstrate that the extract was cytotoxic to HSG and OSCC-3 cells,
      and that cellular degeneration occurred mainly by apoptosis. We believe that oral
      cells could trigger apoptosis after bracken fern induced DNA damage, in order to
      avoid the malignant transformation.

PMID- 19175854
TI  - Evidence for a biphasic apoptotic pathway induced by melatonin in MCF-7 breast
      cancer cells.
AB  - Previous investigations demonstrated that melatonin exerts an oncostatic action
      on estrogen-responsive breast cancer, both in vitro and in vivo. Nevertheless,
      the pro-apoptotic effect of melatonin is still a matter of debate. An
      experimental study was undertaken to focus on melatonin-related apoptosis and to
      identify the apoptotic pathways involved. Whole cell-count, flow-cytometry
      analysis and proteins involved in apoptotic pathways [p53, p73, murine double
      minute 2 (MDM2), caspases-9,-7,-6, cleaved-poly ADP ribose polymerase (PARP), Bcl
      2, Bax and apoptotic inducing factor (AIF)] were investigated in human MCF-7
      breast cancer cells treated with physiological (1 nM) concentration of melatonin.
      Melatonin exerts a significant growth-inhibitory effect on MCF-7 cells, becoming
      evident after 72 hr and thereafter increasing linearly up to 144 hr. In this
      model, the growth-inhibition is transforming growth factor beta 1 (TGFbeta1)
      dependent and it might be reversed by adding an anti-TGFbeta1 antibody. Melatonin
      induces a significant rise in apoptotic rate, at both 24 and 96 hr. The anti
      TGFbeta1 antibody almost completely suppresses melatonin-related late apoptosis;
      however, early apoptosis is unaffected. Early programmed cell death is associated
      with a significant increase in the p53/MDM2 ratio and in AIF release, without
      modifications in caspase activity or cleaved-PARP levels. Activated caspases-9
      and -7 and cleaved-PARP increased significantly at 96 hr, concomitantly with a
      down-regulation of the Bcl-2/Bax ratio. These data suggest that two distinct
      apoptotic processes are triggered by melatonin in MCF-7 cells: an early, TGFbeta1
      and caspase-independent response, and a late apoptotic TGFbeta1-dependent process
      in which activated-caspase-7 is likely to be the terminal effector.

PMID- 19175855
TI  - A novel electrophysiologic effect of melatonin on ischemia/reperfusion-induced
      arrhythmias in isolated rat hearts.
AB  - Reperfusion after a short period of cardiac ischemia triggers ventricular
      arrhythmias attributable to ionic imbalance and oxidative stress. Melatonin
      offers some degree of protection, but its effects on the cardiac action
      potentials are unknown. We evaluated the effects of 5, 10, 20 and 50 microM
      melatonin in isolated perfused rat hearts subjected to 10 min of regional
      ischemia. ECG and membrane potentials were synchronously displayed. After 15 min
      of reperfusion, total antioxidant capacity (TAC) was determined. Melatonin did
      not change the ischemic depolarization nor the action potential amplitude
      depression, but at the end of ischemia the action potential duration (APD)
      decreased in control and 5 microM melatonin-treated hearts. By contrast, it
      returned to preischemic levels in hearts given 20 and 50 microM melatonin.
      Melatonin reduced the incidence of reperfusion arrhythmias from 100% in control
      to 50% in 5 and 10 microM, to 40% in 20 microM and 30% in 50 microM hearts. TAC
      values were higher at all melatonin concentrations. We conclude that melatonin
      reduced the incidence of reperfusion arrhythmias because of its antioxidant
      effects. In addition, at 20 and 50 microM lengthened APD and promoted an improved
      protection. This latter effect should be considered when in vivo applications of
      melatonin are considered.

PMID- 19175856
TI  - Microtubules modulate melatonin receptors involved in phase-shifting circadian
      activity rhythms: in vitro and in vivo evidence.
AB  - MT1 melatonin receptors expressed in Chinese hamster ovary (CHO) cells remain
      sensitive to a melatonin re-challenge even following chronic melatonin exposure
      when microtubules are depolymerized in the cell, an exposure that normally
      results in MT1 receptor desensitization. We extended our findings to MT2
      melatonin receptors using both in vitro and in vivo approaches. Using CHO cells
      expressing human MT2 melatonin receptors, microtubule depolymerization prevents
      the loss in the number of high potency states of the receptor when compared to
      melatonin-treated cells. In addition, microtubule depolymerization increases
      melatonin-induced PKC activity but not PI hydrolysis via Gi proteins similar to
      that shown for MT1Rs. Furthermore, microtubule depolymerization in MT2-CHO cells
      enhances the exchange of GTP on Gi-proteins using a photoaffinity analog of GTP.
      To test whether microtubules are capable of modulating melatonin-induced phase
      shifts, microtubules are depolymerized specifically within the suprachiasmatic
      nucleus of the hypothalamus (SCN) of the Long Evans rat and the efficacy of
      melatonin to phase shift their circadian activity rhythms was assessed and
      compared to animals with intact SCN microtubules. We find that microtubule
      depolymerization in the SCN using either Colcemid or nocodazole enhances the
      efficacy of 10 pm melatonin to phase-shift the activity rhythms of the Long Evans
      rat. No enhancement occurs in the presence of beta-lumicolchicine, the inactive
      analog of Colcemid. Taken together, these data suggest that microtubule dynamics
      can modulate melatonin-induced phase shifts of circadian activity rhythms which
      may explain, in part, why circadian disturbances occur in individuals afflicted
      with diseases associated with microtubule disturbances.

PMID- 19175857
TI  - Modulation of the cGMP signaling pathway by melatonin in pancreatic beta-cells.
AB  - Melatonin influences the second messenger cyclic guanosine 3',5'-monophosphate
      (cGMP) signaling pathway in pancreatic beta-cells via a receptor-mediated
      mechanism. In the present study, it was determined how the regulation of cGMP
      concentrations by melatonin proceeds. The results provide evidence that melatonin
      acts via the soluble guanylate cyclase (sGC), as molecular investigations
      demonstrated that long-term incubation with melatonin significantly reduced the
      expression levels of the sGC mRNA in rat insulinoma beta-cells (INS1) cells,
      whereas mRNA expression of membrane guanylate cyclases was unaffected. Incubation
      with melatonin abolished the S-nitrosoacetyl penicillamine-induced increase of
      cGMP concentrations in INS1 cells. In addition, the cGMP-inhibitory effect of
      melatonin was reversed by preincubation with the sGC inhibitors 1H
      (1,2,4)oxadiazolo(4,3-alpha)quinoxalin-1-one and 4H-8-bromo-1,2,4-oxadiazolo(3,4
      d)benz(b)(1,4)oxazin-1-one. Nitric oxide (NO) production was not influenced after
      1 hr of melatonin application, but was influenced after a 4 hr incubation period.
      Preincubation of INS1 cells with the NO synthase inhibitor N(G)-monomethyl-l
      arginine did not abolish the cGMP-inhibitory effect of melatonin. Transcripts of
      cyclic nucleotide-gated (CNG) channels were significantly reduced after melatonin
      treatment in a dose-dependent manner, indicating the involvement of these
      channels in mediating the melatonin effect in INS1 cells. The results of this
      study demonstrate that melatonin mediates its inhibitory effect on cGMP
      concentrations in pancreatic beta-cells by inhibiting the sGC, but does not
      influence NO concentration or NO synthase activity in short-term incubation
      experiments. In addition, it was demonstrated that melatonin is involved in
      modulation of CNG channel mRNA.

PMID- 19175858
TI  - The role of chloride channels in rat corpus cavernosum: in vivo study.
AB  - INTRODUCTION: Recent studies have identified the existence of outward,
      depolarizing chloride currents in isolated rat, rabbit, and human corpus
      cavernosum muscle cells. However, few articles have demonstrated the functional
      role of chloride channels in vivo in corpus cavernosum smooth muscle. Aim. To
      investigate the role of calcium-dependent chloride channels in erectile function
      of rat corpus cavernosum smooth muscle. METHODS: Adult male Wistar rats were used
      to perform an in vivo study in a rat model of erection. Both crura of the rats
      were isolated to in order to record intracavernosal pressure (ICP) during basal
      conditions and electrical stimulation of erection, with and without
      intracorporeal injection of norepinephrine, chloride transport inhibitors, and
      chloride channel blockers. MAIN OUTCOME MEASURE: ICP. RESULTS: ICP increased as
      the amplitude of electrical stimulation increased, and decreased in a dose
      dependent manner (during electrical stimulation) as norepinephrine injection
      strength increased. Injection into the corpus cavernosum of the Cl(-) channel
      blockers, niflumic acid, anthracene-9-carboxylic acid, and 4,4'-diisothiocyano
      2,2'-stilbene-disulfonic acid increased ICP. Injection into the corpus cavernosum
      of the Cl(-) channel transport inhibitors bumetanide, ethacrynic acid, and HCO(3)
      free 4-(2-hydroxyethyl )-1-1- piperazine ethanesulphonic acid buffer, and also
      increase the ICP. The effects of both Cl(-) channel blockers and Cl(-) channel
      transport inhibitors on ICP were concentration-dependent. CONCLUSIONS: Our
      findings suggest that chloride channels play an important role in the regulation
      of corpus cavernous smooth muscle tone in vivo.

PMID- 19175859
TI  - Metoidioplasty as a single stage sex reassignment surgery in female transsexuals:
      Belgrade experience.
AB  - INTRODUCTION: Metoidioplasty represents one of the variants of phalloplasty in
      female transsexuals. Its main characteristic is that it is a one-stage procedure.
      It involves lengthening and straightening of hypertrophied clitoris to create a
      neophallus, urethral lengthening to enable voiding while standing, and scrotal
      reconstruction with insertion of testicle prostheses. AIM: Our aim is to describe
      our technique and highlight its advantages. METHODS: Between September 2002 and
      April 2007, 82 female transsexuals, aged 18-54 years (mean age 31) underwent one
      stage metoidioplasty. Clitoris is lengthened and straightened by division of
      clitoral ligaments and short urethral plate. Urethroplasty is done with combined
      buccal mucosa graft and genital skin flaps. Scrotum is created from labia majora
      in which two testicle prostheses are inserted. Simultaneously, female genitalia
      are removed. MAIN OUTCOME MEASURES: Patients' personal satisfaction about
      sensitivity and length of neophallus, possibility to void in standing position,
      real length of reconstructed urethra as well as complication rate comparing to
      other published data. RESULTS: The median follow-up was 32 months (range 14-69).
      The mean neophallic length was 5.7 cm (range 4-10). Voiding in standing position
      was reported in all patients, while dribbling and spraying were noticed in 23
      cases and solved spontaneously. There were two urethral strictures and seven
      fistulas that required secondary minor revision. All patients reported preserved
      sensation and normal postoperative erection. Testicle prostheses rejection was
      not observed in any of the patients. CONCLUSIONS: Metoidioplasty is a single
      stage and time-saving procedure. It could be an alternative to total phalloplasty
      in female transsexuals who do not wish to have sexual intercourse. Also, it
      represents a first step in cases where additional augmentation phalloplasty is
      required.

PMID- 19175860
TI  - Erectile dysfunction management options in Nigeria.
AB  - INTRODUCTION: In Nigeria, the prevalence of erectile dysfunction (ED) among
      patients attending primary care clinics, age-standardized to the U.S. population
      in 2000 is 57.4%. This is considered high enough to warrant the attention of
      scientist for critical studies and analysis. The high ED prevalence is associated
      with etiologies such as psychosexual factors, chronic medical conditions, and
      some lifestyles. ED constitutes a major public health problem, influencing the
      patient's well-being and quality of life. It also leads to broken homes and
      marriages, psychological, social, and physical morbidity. AIM: To give an account
      of various ED management options in Nigeria. METHOD: Review of peer-reviewed
      literature, questionnaire, and ethnobotanical survey to some indigenous herb
      sellers and herbalists. MAIN OUTCOME MEASURES: Cross cultural perspectives of ED
      management in Nigeria. RESULTS: The review suggests that traditional
      (phytotherapy, zootherapy, and occultism) and nontraditional, orthodox practice
      (drug therapy, psychological, and behavioral counseling) are applicable to ED
      management in Nigeria. CONCLUSION: This review should help in creating awareness
      into various options available for managing ED in the country, but does not
      recommend self medication of any form, be it the use of orthodox or herbal
      remedy.

PMID- 19175861
TI  - Sex differences in visual attention to sexually explicit videos: a preliminary
      study.
AB  - INTRODUCTION: Although men appear to be more interested in sexual stimuli than
      women, this difference is not completely understood. Eye-tracking technology has
      been used to investigate visual attention to still sexual images; however, it has
      not been applied to moving sexual images. AIM: To investigate whether sex
      difference exists in visual attention to sexual videos. METHODS: Eleven male and
      11 female healthy volunteers were studied by our new methodology. MAIN OUTCOME
      MEASURES: The subjects viewed two sexual videos (one depicting sexual intercourse
      and one not) in which several regions were designated for eye-gaze analysis in
      each frame. Visual attention was measured across each designated region according
      to gaze duration. Sex differences, the region attracting the most attention, and
      visually favored sex were evaluated. RESULTS: In the nonintercourse clip, gaze
      time for the face and body of the actress was significantly shorter among women
      than among men. Gaze time for the face and body of the actor and nonhuman regions
      was significantly longer for women than men. The region attracting the most
      attention was the face of the actress for both men and women. Men viewed the
      opposite sex for a significantly longer period than did women, and women viewed
      their own sex for a significantly longer period than did men. However, gaze times
      for the clip showing intercourse were not significantly different between sexes.
      CONCLUSIONS: A sex difference existed in visual attention to a sexual video
      without heterosexual intercourse; men viewed the opposite sex for longer periods
      than did women, and women viewed the same sex for longer periods than did men.
      There was no statistically significant sex difference in viewing patterns in a
      sexual video showing heterosexual intercourse, and we speculate that men and
      women may have similar visual attention patterns if the sexual stimuli are
      sufficiently explicit.

PMID- 19175862
TI  - Isolated polyarteritis nodosa of the genitourinary tract presenting with severe
      erectile dysfunction: a case report with long-term follow-up.
AB  - INTRODUCTION: Polyarteritis nodosa (PAN) is a rare necrotizing vasculitis
      affecting small- and medium-sized arteries of multiple organs. Spreading to the
      genitourinary tract is very common, with invariable involvement of kidneys or
      testes, but its impact on erectile function remains undetermined. AIM: We
      describe a case of isolated PAN of the genitourinary tract diagnosed in a young
      man presenting with severe erectile dysfunction (ED), debate the critical issues
      of the differential diagnosis, and provide the long-term follow-up outcome.
      METHODS: The case report profiled a 36-year-old man who presented with
      progressively worsening erectile function and was incidentally found to suffer
      from genitourinary PAN. Extensive clinical, laboratory, and instrumental
      investigations, including brachial artery dilation test, suggested an
      arteriogenic etiology for ED and excluded a systemic involvement by PAN.
      Management featured use of a long-term, on-demand phosphodiesterase type 5 (PDE5)
      inhibitor regimen for ED, and close surveillance with no immunosuppressive
      therapy for PAN. MAIN OUTCOME MEASURES: Clinical history data, brachial artery
      dilation test, response to PDE5 inhibitor therapy. RESULTS: After 12 months of
      PDE5 inhibitor therapy, the patient recovered a normal erectile function,
      paralleled by restored endothelial function as assessed with brachial artery
      dilation test. At a 5-year clinical follow-up, he continued to have full erectile
      ability with only occasional use of PDE5 inhibitor, and no evidence of
      progressive PAN was documented. CONCLUSIONS: We propose PAN as a novel cause of
      arteriogenic ED, report the effective therapy with PDE5 inhibitor, and confirm
      the good long-term prognosis of isolated genitourinary PAN without
      immunosuppressive treatment.

PMID- 19175863
TI  - Losartan, an Angiotensin type I receptor, restores erectile function by
      downregulation of cavernous renin-angiotensin system in streptozocin-induced
      diabetic rats.
AB  - INTRODUCTION: The high incidence of erectile dysfunction (ED) in diabetes
      highlights the need for good treatment strategies. Recent evidence indicates that
      blockade of the angiotensin type I receptor (AT1) may reverse ED from various
      diseases. AIM: To explore the role of cavernous renin-angiotensin system (RAS) in
      the pathogenesis of diabetic ED and the role of losartan in the treatment of
      diabetic ED. METHODS: The AT1 blocker (ARB) losartan (30 mg/kg/d) was
      administered to rats with streptozocin (65 mg/kg)-induced diabetes. Erectile
      function, cavernous structure, and tissue gene and protein expression of RAS in
      the corpora cavernosa were studied. MAIN OUTCOME MEASURE: We sought to determine
      the changes of cavernous RAS in the condition of diabetes and after treatment
      with losartan. RESULTS: RAS components (angiotensinogen, [pro]renin receptor,
      angiotensin-converting enzyme [ACE], and AT1) were expressed in cavernosal
      tissue. In diabetic rats, RAS components were upregulated, resulting in the
      increased concentration of angiotensin II (Ang II) in the corpora. A positive
      feedback loop for Ang II formation in cavernosum was also identified, which could
      contribute to overactivity of cavernous RAS in diabetic rats. Administration of
      losartan blocked the effect of Ang II, downregulated the expression of AT1 and
      Ang II generated locally, and partially restored erectile function (losartan
      treated group revealed an improved intracavernous pressure/mean systemic arterial
      pressure ratio as compared with the diabetic group (0.480 +/- 0.031 vs. 0.329 +/-
      0.020, P < 0.01). However, losartan could not elevate the reduced smooth
      muscle/collagen ratio in diabetic rats. CONCLUSIONS: The cavernous RAS plays a
      role in modulating erectile function in corpora cavernosa and is involved in the
      pathogenesis of diabetic ED. ARB can restore diabetic ED through downregulating
      cavernous RAS.

PMID- 19175864
TI  - The social context for psychological distress from iatrogenic gynecomastia with
      suggestions for its management.
AB  - INTRODUCTION: Gynecomastia (breast development in males) is a side effect of
      androgen deprivation therapy (ADT) for prostate cancer (PCa). Medical
      interventions to prevent or treat gynecomastia carry risk of additional
      detrimental side effects. However, untreated gynecomastia can be physically
      uncomfortable and psychologically distressing. Shame from gynecomastia can lead
      patients to stop otherwise beneficial exercise. AIMS: Our first aim is to explore
      the social context for gynecomastia and how it is interpreted by men with the
      condition, as well as by others, both male and female. Subsequently, we use our
      understanding of why gynecomastia is psychologically distressing to propose
      psychosocial interventions that could help men accept this side effect of ADT.
      METHODS: We draw on academic literature, media accounts, and web-based
      testimonials from men with gynecomastia, to understand how gynecomastia is
      perceived by both patients and the medical community. We examine these resources
      in light of gynecomastia's impact on sex roles, sexuality, and gender identity
      issues. MAIN OUTCOME MEASURES: By exploring what breasts in a male mean to the
      individual, we produce an understanding of the social context for distress from
      gynecomastia. From this understanding, we derive hypotheses about who might be
      most distressed from gynecomastia and strategies for alleviating this distress.
      RESULTS: The shame and stigma of gynecomastia is linked to the objectification of
      women. We suggest that men fear that their breasts will marginalize and
      subordinate them within gender hierarchies. There is little evidence that breasts
      on a male erotically attract either men or women. Novel options for living with
      gynecomastia are contrasted with medicalized strategies including mastectomy.
      CONCLUSION: Assessment instruments need to be developed to identify patients most
      likely to experience distress from gynecomastia and seek out medical
      interventions. Surgical, radiological, or pharmacological interventions may not
      be universally necessary if greater acceptance of gynecomastia is made available
      through psychosocial support programs. For example, PCa patients may learn to
      accept gynecomastia through reconceptualizing their breasts as autoerotic.
      Support programs modeled on those of the breast cancer community, including
      Encore and dragon boat racing, may also help to build communities to serve
      patients with gynecomastia while defending individuals against shame, isolation,
      and loss of self-esteem.

PMID- 19175865
TI  - Sexual and reproductive health knowledge in cystic fibrosis female patients and
      their parents.
AB  - INTRODUCTION: The changing outcomes for young cystic fibrosis (CF) patients means
      that reproductive health issues have become an integral part of CF management.
      AIM: The aim of this study was to investigate the knowledge and experiences of
      reproductive and sexual health issues in women with CF and to investigate the
      knowledge and reproductive health attitudes of their parents. MAIN OUTCOME
      MEASURES: Assessment of reproductive and sexual health knowledge in female CF
      patients and their parents. METHODS: A questionnaire study directed to 120 Polish
      women with CF aged 16 years and older and their parents. RESULTS: Sixty-four
      patients and their parents responded to the questionnaire. Sixty-eight percent of
      the patients started sexual intercourse at a mean age of 19.2 years. Eighty-four
      percent of all sexually active women reported that they did not use any form of
      contraception. Only 32.8% of women understood the problems connected with their
      own and male fertility in CF. Popular scientific publications and other CF
      patients were identified as the most important source of information. Only 23% of
      parents understood the problems connected with female fertility in CF; 44% of
      parents thought that man with CF had normal fertility. Seventy-five percent of
      the women and 40% of the parents felt that sexual health discussions should begin
      between age 12 and 14 years with a CF doctor and the mother. CONCLUSIONS: Our
      study showed that significant knowledge gaps exist regarding fertility issues in
      both CF patients and CF parents. Women with CF have some general knowledge about
      sexual issues but insufficient knowledge to have a safe sexual life. The results
      helped us to develop the educational program for CF patients.

PMID- 19175866
TI  - The sexuality and quality of life of hemodialyzed patients--ASED multicenter
      study.
AB  - INTRODUCTION: Chronic kidney disease (CKD) strongly affects sexual function (SF)
      and quality of life (QoL). The relations between CKD, SF, mental health, and QoL
      remain poorly understood in dialyzed patients. AIM: To correlate sexuality to QoL
      in hemodialysis patients. METHODS: One hundred twelve patients (69 males and 43
      females) aged 20-60 years at six dialysis units were interviewed, and their
      medical records were reinvestigated and supplemented with completed Beck's
      Depression Inventory, Self-Evaluation Questionnaire, Mell-Krat Scale,
      International Index of Erectile Function-5, Arizona Sexual Experience Scale, and
      health-related Quality of Life (Short Form [SF]-36) questionnaires. MAIN OUTCOME
      MEASURES: Prevalence of different levels of measurable aspects of sexual life,
      mental health, QoL, as well as their correlations, was assessed. RESULTS: Only
      55.4% of the patients were sexually active (79% in the age-matched general
      population) and 24.1% has ever before spoken to a doctor about their sexual life.
      The patients perceived sexual activity as important and were not satisfied with
      the performance. The predominant sexual dysfunctions were loss or diminished
      sexual needs (84.7% males and 48.8% females); in men, also erectile dysfunction
      (44.5%) and inhibited or lack of ejaculation (51.5%); in women, arousal
      dysfunction and anorgasmia (67.8% and 80.7%, respectively). The rate of
      depression was extremely high (80.5%). The patients self-assessed their QoL as
      low in both the physical and the mental health domains. Multiple regression
      analysis revealed that anxiety in men and depression in women independently
      predicted the lower quality of sexual life (P = 0.017 and 0.04, respectively).
      The general QoL, mental health, and physical health negatively correlated with
      the presence of depressive symptoms (P = 0.011, 0.013, and 0.011, respectively).
      CONCLUSIONS: This pilot study is the first to present, in a multicenter design,
      the complex relations of sexuality and QoL in hemodialyzed patients, which are
      strongly underevaluated by medical professionals. It supports a thesis that
      sexual disability correlates with depression and anxiety, and seriously impacts
      the QoL in dialyzed patients.

PMID- 19175867
TI  - Functional characterization of nonadrenergic noncholinergic neurotransmitter
      release via endocannabinoids: an in vitro study in rabbit corpus cavernosum.
AB  - INTRODUCTION: Corporal smooth muscle relaxation is mediated mainly but not
      completely by nitric oxide. Endocannabinoids modulate the various
      neurotransmitter systems. AIM: In the present study, a possible role of
      endocannabinoids on non-nitrergic nonadrenergic noncholinergic (NANC)-mediated
      relaxations was investigated. METHODS: In precontracted tissues, control
      electrical field stimulation (EFS)-induced NANC relaxation responses were
      obtained using varying frequencies of stimulation in the presence of L-arginine
      methyl ester (L-NAME), guanethidine, and atropine. To investigate the effects of
      cannabinoids on EFS-evoked non-nitrergic NANC relaxation responses, a similar
      experimental procedure was applied in the presence of cannabinoid receptor
      antagonists AM251 or AM630; vanilloid receptor antagonist capsazepine; or
      cannabinoid receptor agonists anandamide, arachidonyl-2-chloroethylamide (ACEA),
      or JHW015. MAIN OUTCOME MEASURES: Effects of cannabinoid receptor antagonists and
      agonists on EFS-evoked non-nitrergic NANC relaxation responses. RESULTS: L-NAME
      abolished EFS-induced relaxation responses at lower frequencies (2-4 Hz) and
      inhibited the relaxation responses at higher frequencies (8-32 Hz). AM251 and
      AM630 either together or separately inhibited, whereas anandamide, ACEA, and
      JHW015 enhanced non-nitrergic NANC relaxation responses. Anandamide did not alter
      EFS-induced non-nitrergic NANC relaxations in the presence of AM251 and AM630.
      Capsazepine enhanced non-nitrergic NANC relaxation responses. CONCLUSION: These
      results suggest that non-nitrergic NANC relaxations may be mediated partially by
      cannabinoid-like neuronal factors acting at both cannabinoid CB(1) and
      cannabinoid CB(2) receptors.

PMID- 19175868
TI  - Inverse association between hepatic stellate cell apoptosis and fibrosis in
      chronic hepatitis C virus infection.
AB  - Perisinusoidal hepatic stellate cells (HSC) are the principal fibrogenic cells in
      the liver. In animal models, HSC apoptosis is the predominant clearance mechanism
      of activated HSC, although data evaluating whether the same processes occur in
      humans are limited. We conducted a cross-sectional study to evaluate the
      association between HSC apoptosis and fibrosis stage in subjects with chronic
      hepatitis C virus (HCV) infection (n = 44) and HCV-negative controls with normal
      liver histology (n = 9). We used immunohistochemical techniques to identify
      activated (alpha-smooth muscle actin+), proliferative (Ki-67+) and apoptotic
      (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end-labelling+)
      HSC in liver biopsy specimens from all subjects. The same pathologist enumerated
      positive cells per high-power field (HPF, x 200) in 20 periportal/lobular areas.
      HSC apoptosis was decreased in HCV-positive subjects compared with controls
      (median 0.4, range 0.0-3.1 vs 1.1, 0.2-3.5 cells/HPF, P = 0.02). Among HCV
      positive subjects, HSC apoptosis was decreased in those with moderate to advanced
      fibrosis (P = 0.04) compared with those with mild fibrosis. By multivariate
      analysis, HSC apoptosis decreased by an average of 0.14 cells/HPF (95% confidence
      interval 0.01-0.28 cells/HPF) per increase in fibrosis stage (P = 0.04). While
      the number of activated and proliferative HSC was significantly increased in HCV
      infected subjects compared with that in uninfected controls, the numbers of these
      cells did not differ between HCV-infected subjects with mild vs moderate/advanced
      fibrosis. In conclusion, the number of apoptotic HSC was significantly decreased
      in HCV-infected subjects with advanced fibrosis. In chronic HCV infection,
      inhibition of HSC apoptosis may be one mechanism by which fibrosis progresses.

PMID- 19175869
TI  - Lack of de novo hepatitis C virus infections and absence of nosocomial
      transmissions of GB virus C in a large cohort of German haemodialysis patients.
AB  - To determine the prevalence and incidence of hepatitis C virus (HCV) infections
      among haemodialysis patients, a large prospective multicentre trial was conducted
      in the German Federal State of North Rhine-Westphalia. Sera obtained from the
      recruited patients in two separate sampling rounds run 1 year apart were analysed
      for both anti-HCV antibodies and HCV RNA. HCV RNA positive samples were also
      genotyped by direct sequencing of an HCV core fragment. In the first and second
      rounds, 150 (5.2%) of 2909 and 114 (5.4%) of 2100 patients were anti-HCV
      positive, respectively, and 4% of individuals were viraemic. Evaluation of
      potential risk factors in a case-control study indicated that the factors
      'foreign country of birth', 'blood transfusions given before 1991' and 'duration
      of treatment on haemodialysis' were associated with the risk of HCV infection.
      Among the 2100 patients of whom 'paired' serum samples from both rounds were
      available for testing, not a single 'de novo' HCV infection could be recorded.
      The fact that in a subset of about 20% of these patients no nosocomial GB virus C
      (GBV-C) transmission occurred during the observational period suggests that the
      lack of HCV seroconversions was not only attributable to the isolation of HCV
      infected patients but also to the strict adherence to so-called universal
      hygienic precautions for infection control maintained in the participating
      dialysis centres.

PMID- 19175870
TI  - An independent and prospective comparison of two commercial fibrosis marker
      panels (HCV FibroSURE and FIBROSpect II) during albinterferon alfa-2b combination
      therapy for chronic hepatitis C.
AB  - SUMMARY: Noninvasive markers that accurately follow changes in fibrosis may
      provide alternatives to liver biopsy for assessment of histological endpoints of
      antiviral therapy in chronic hepatitis C (CHC). This study compared two
      commercially available serum marker panels (HCV FibroSURE and FIBROSpect II)
      during interferon-based therapy. Ninety-five interferon-naive patients with
      genotype 1 CHC were enrolled in a phase 2b, active-controlled study of
      albinterferon alfa-2b/ribavirin for 48 weeks. Proprietary and simple biochemical
      marker panels were independently evaluated in serum before and during the study.
      Baseline liver biopsies were evaluated for METAVIR fibrosis by a single
      pathologist. Index scores were obtained for HCV FibroSURE (n = 84) and FIBROSpect
      II (n = 95); mean biopsy length: 17.8 +/- 8.0 mm. For detecting fibrosis stages 2
      4 (prevalence 23% [22/95] and 21% [18/84]), HCV FibroSURE and FIBROSpect II
      indicated high sensitivity (1.00 and 0.95, respectively), lower but comparable
      specificity (0.61 and 0.66, respectively), and a good area under the receiver
      operating characteristic curve (0.89 and 0.90, respectively). Simple indices had
      high indeterminate rates (31-40%) at baseline. Patients with a sustained
      virological response had lower baseline scores than nonresponders, and reduced
      median percent changes in index scores for HCV FibroSURE (-20.0%vs 2.9%; P =
      0.14) and FIBROS Spect II (-6.8%vs 18.4%; P = 0.05). The panels demonstrated
      comparable performance characteristics for differentiating mild from moderate
      severe stage disease in CHC. Lower index scores at baseline that continue to
      decline likely reflect reduced fibrogenesis activity in patients with successful
      antiviral responses to therapy.

PMID- 19175871
TI  - Impact of adefovir dipivoxil on liver fibrosis and activity assessed with
      biochemical markers (FibroTest-ActiTest) in patients infected by hepatitis B
      virus.
AB  - SUMMARY: The aim was to assess the utility of FibroTest-ActiTest (FT-AT) as
      noninvasive markers of histological changes in patients with chronic hepatitis.
      Patients with chronic hepatitis B (HBeAg+ and HBeAg-) randomized in two trials of
      adefovir (ADV) vs placebo, with available paired liver biopsies and FT-AT at
      baseline and after 48 weeks of treatment were included. The predictive value of
      FT-AT was assessed using the area under the receiver operating characteristics
      curves (AUROCs) for the diagnosis of bridging fibrosis, cirrhosis and moderate
      severe necroinflammatory activity. The impact of treatment with ADV vs placebo
      was assessed on liver injury according to baseline stage and virological response
      at 48 weeks. The analysis of 924 estimates for the diagnosis of bridging
      fibrosis, cirrhosis and moderate or severe necroinflammatory activity yielded FT
      AT AUROCs: 0.76 +/- 0.02 (standardized 0.81 +/- 0.02), 0.81 +/- 0.02 and 0.80 +/-
      0.01, respectively. Similar impacts of ADV on liver fibrosis and activity were
      observed both with paired biopsy (fibrosis stage from 1.6 to 1.4, activity grade
      from 2.5 to 1.3) and paired biomarkers (FT from 0.44 to 0.40, AT from 0.62 to
      0.25) (P < 0.0001). FibroTest-ActiTest provides a quantitative estimate of liver
      fibrosis and necroinflammatory activity in patients with chronic hepatitis B and
      may be an alternative to reduce the need for liver biopsy.

PMID- 19175872
TI  - Reverse genetic analysis of a putative, influenza virus M2 HXXXW-like motif in
      the p7 protein of hepatitis C virus.
AB  - SUMMARY: The p7 protein of hepatitis C virus (HCV) has been classified into a
      family of viral proteins, designated viroporins that form ion channels. The M2
      protein of influenza virus is the prototype viroporin and encodes a HXXXW motif
      that constitutes the main functional element of the M2 channels. Alignment of
      different p7 proteins revealed that a HXXXW sequence (positions 17-21) is also
      highly conserved among some HCV genotypes. To study the putative HXXXW motif in
      p7, five mutants of the Japanese fulminant hepatitis 1 strain of HCV that encoded
      H17A, H17G, H17E, Y21A and Y21W were generated. After transfection of human
      hepatoma cells with the mutant transcripts, unlike H17A and H17G that produced up
      to 1 log lower viral titres than wild type, H17E and Y21W showed slightly higher
      infectivity. In conclusion, this study demonstrated that the HXXXW sequence
      exists in the p7 proteins of some HCV genotypes and that H17 plays an important
      role in virus replication.

PMID- 19175873
TI  - The influence of North American Aboriginal ethnicity on pro-inflammatory and anti
      inflammatory cytokine responses to IFN-alpha.
AB  - North American Aboriginals have an enhanced propensity to clear HCV infection.
      Interferon (IFN)-alpha is a critical agent in the clearance of hepatitis C virus
      (HCV) and other viruses; therefore the influence of Aboriginal ethnicity on IFN
      alpha responses was investigated in healthy Caucasian population control and
      Aboriginal cohorts. Cohort peripheral blood mononuclear cells produced similar
      levels of IFN-alpha upon culture with reovirus, an innocuous virus capable of
      triggering IFN-alpha synthesis. In addition, similar IFN-gamma synthesis was
      observed in the presence IFN-alpha or reovirus. In contrast, Caucasian
      supernatants exhibited greater IL-10 levels (P<0.005), contributing to the
      overall cytokine balance as assessed by IFN-gamma/IL-10 ratios being consistently
      elevated in the Aboriginal cohort. The potential of HCV proteins to alter IFN
      alpha cytokine induction was also investigated. Although there was some
      indication that HCV proteins might increase IFN-alpha induced IL-10 synthesis in
      Caucasians and conversely, IFN-gamma synthesis in Aboriginals, the addition of
      HCV proteins did not influence IFN-gamma/IL-10 ratios. Finally, signal transducer
      and activator of transcription (STAT) 3 nuclear translocation was examined by
      western blot because it is a required intermediate in IFN-alpha induced IL-10
      synthesis. Supporting the differential IL-10 production, IFN-alpha and core
      synergistically enhanced STAT3 nuclear translocation in Caucasian (P<0.05);
      whereas, nuclear translocation of STAT3 remained unchanged in Aboriginal cells.
      Taken together, these findings suggest that ethnicity may influence certain
      responses to IFN-alpha, possibly even in the presence of viral agents. These
      differences could impact early immune events allowing for enhanced viral
      clearance in Aboriginal populations.

PMID- 19175874
TI  - Thyroid function and changes in ultrasound morphology during antiviral therapy
      with pegylated interferon and ribavirin in patients with chronic hepatitis C.
AB  - SUMMARY: Thyroid disease is a common side-effect of interferon-based antiviral
      therapy for chronic hepatitis C, which may lead to dose reduction or
      discontinuation of therapy. The aim of this study was to investigate changes in
      ultrasound morphology, thyroid function, autoimmunity as well as predictive
      factors for the development of thyroid dysfunction in patients with hepatitis C
      virus infection treated with pegylated interferon-alpha (PEG-IFN-alpha) and
      ribavirin. A total of 59 patients with chronic hepatitis C assigned for antiviral
      treatment with PEG-IFN-alpha and ribavirin were enrolled into the study. All
      patients were subjected to an ultrasound examination of the thyroid gland before
      treatment, and after 1, 3 and 6 months of antiviral therapy. In addition, thyroid
      function and autoimmune status were determined at fixed time-points. Prior and
      during the course of therapy, 11 patients (19%) developed thyroid dysfunction
      (one hypothyroidism, nine hyperthyroidism, one hyperthyroidism followed by
      hypothyroidism). Hyperthyroidism was shown to be Graves' disease in one patient
      and destructive thyroiditis in nine patients. Power-Doppler ultrasound could
      differentiate between destructive thyroiditis and Graves' disease. A reduction in
      echogenicity suggestive for a destructive process of the thyroid gland was
      observed even before changes in thyroid function of antibody status could be
      measured. Risk factors for the development of thyroid dysfunction were age,
      female gender, pre-treatment thyroid volume, pre-existing thyroglobulin/thyroid
      peroxidase antibodies and viral load. Changes in thyroid function are a common
      side-effect occurring during antiviral therapy with PEG-IFN-alpha and ribavirin.
      Ultrasound presents a simple complementary tool for screening and follow-up
      during antiviral therapy, which helps to differentiate between the common types
      of hyperthyroidism and gives insight into morphological changes of the thyroid
      gland during antiviral therapy.

PMID- 19175875
TI  - Changes of non-invasive markers and FibroScan values during HCV treatment.
AB  - The recent advent of non-invasive methods for assessment of fibrosis allows
      serial assessments in all patients with hepatitis C. The aim of this prospective
      study was to evaluate changes in liver fibrosis, as measured with non-invasive
      methods, in a large cohort of HCV-infected patients with and without treatment.
      From May 2003 through March 2006, all previously untreated HCV-infected patients
      were enrolled in this study. Liver fibrosis was staged with FibroScan and
      Fibrotest at inclusion, then every year in untreated patients, and at the end of
      treatment and 6 months later in treated patients. The study population consisted
      of 416 patients, of whom 112 started treatment after enrolment. In the treatment
      group, FibroScan and Fibrotest values were significantly higher before and after
      treatment than in untreated patients at baseline and after 1 year. However, there
      was no significant difference between treated and untreated patients at the end
      of follow-up. FibroScan and Fibrotest values fell in all treated patients,
      whatever their virological response. In multivariate analysis, treatment was the
      only factor independently associated with a fall in the FibroScan value. In
      conclusion, whatever the virological response, treatment for HCV infection is
      associated with an improvement of FibroScan and Fibrotest values. Further studies
      are needed to compare these non-invasive methods with liver biopsy. These non
      invasive methods, and especially FibroScan, should be useful for assessing
      treatment efficacy in clinical trials of new drugs.

PMID- 19175876
TI  - FibroScan used in street-based outreach for drug users is useful for hepatitis C
      virus screening and management: a prospective study.
AB  - Although hepatitis C virus (HCV) infection prevalence is high among drug users,
      they do not commonly receive regular care in academic centres. The aim of this
      prospective study was to assess the influence of FibroScan use on HCV screening
      and management in street-based outreach. From January 2006 to January 2007, all
      consecutive drug users were offered noninvasive evaluation of liver fibrosis with
      FibroScan. After FibroScan, parameters were recorded with a structured, face-to
      face questionnaire by outreach workers. All 298 subjects accepted FibroScan
      evaluation drug use was--ever injected heroin (69%), ever snorted or injected
      cocaine (89%), current chronic alcohol abuse (44%). The median FibroScan score
      was 5.3 kPa. Before blood sampling, 34% of subjects reported HCV positivity. HCV
      positivity was found in 83 cases. All these subjects had positive HCV-RNA. Forty
      five subjects agreed to meet a hepatologist. By multivariate analysis, never
      snorted cocaine, consumed alcohol < 21 drinks per week, duration of injected
      heroin > 7 years, and FibroScan > 7.1 kPa were significantly associated with HCV
      positivity. Thus in a street-based outreach service for drug users, the
      acceptance of FibroScan is excellent. FibroScan with a hospital-based physician
      may facilitate screening and management of drug users for HCV infection.

PMID- 19175877
TI  - Role of antiviral therapy in the prevention of perinatal transmission of
      hepatitis B virus infection.

PMID- 19175878
TI  - Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B
      virus infection: a multicentre, randomized, double-blind, placebo-controlled
      study.
AB  - This randomized, double-blind, placebo-controlled study evaluated whether
      lamivudine given during late pregnancy can reduce hepatitis B virus (HBV)
      perinatal transmission in highly viraemic mothers. Mothers were randomized to
      either lamivudine 100 mg or placebo from week 32 of gestation to week 4
      postpartum. At birth, infants received recombinant HBV vaccine with or without
      HBIg and were followed until week 52. One hundred and fifty mothers, with a
      gestational age of 26-30 weeks and serum HBV DNA >1000 MEq/mL (bDNA assay), were
      treated. A total of 141 infants received immunoprophylaxis at birth. In
      lamivudine-treated mothers, 56 infants received vaccine + HBIg (lamivudine +
      vaccine + HBIg) and 26 infants received vaccine (lamivudine + vaccine). In
      placebo-treated mothers, 59 infants received vaccine + HBIg (placebo + vaccine +
      HBIg). At week 52, in the primary analyses where missing data was counted as
      failures, infants in the lamivudine + vaccine + HBIg group had a significant
      decrease in incidence of HBsAg seropositivity (10/56, 18%vs 23/59, 39%; P =
      0.014) and in detectable HBV DNA (11/56, 20%vs 27/59, 46%; P = 0.003) compared to
      infants in the placebo + vaccine + HBIg group. Sensitivity analyses to evaluate
      the impact of missing data at week 52 resulting from a high dropout rate (13% in
      the lamivudine + vaccine + HBIg group and 31% in the placebo + vaccine + HBIg
      group) remained consistent with the primary analysis in that lower transmission
      rates were still observed in the infants of lamivudine-treated mothers, but the
      differences were not statistically significant. No safety concerns were noted in
      the lamivudine-treated mothers or their infants. Results of this study suggest
      that lamivudine reduced HBV transmission from highly viraemic mothers to their
      infants who received passive/active immunization.

PMID- 19175879
TI  - Improving blood-borne viral diagnosis; clinical audit of the uptake of dried
      blood spot testing offered by a substance misuse service.
AB  - SUMMARY: The diagnosis of blood-borne viral infection amongst drug injectors in
      Wales is limited by a poor uptake of diagnostic testing; recent research suggests
      that dried blood spot (DBS) sample collection, rather than venepuncture, may
      improve diagnostic rates. We carried out an audit of the uptake of DBS testing
      for hepatitis C, hepatitis B and HIV amongst drug injectors attending a substance
      misuse service (SMS) in the first year of DBS testing being routinely offered to
      clients (1 May 2007 to 30 April 2008) and compared the uptake to venepuncture
      testing of SMS clients in the previous year. Uptake of DBS testing for hepatitis
      C, hepatitis B and HIV was almost six times greater than the uptake of
      venepuncture testing amongst clients of the SMS in the previous year. The data
      are consistent with the hypothesis that DBS testing can increase the uptake of
      blood-borne viral testing amongst current and ex-drug injectors. We accept that
      part of the almost sixfold increase in diagnostic testing observed in the first
      year of DBS testing may be due to an increase in awareness amongst drug injectors
      of testing opportunities and a prioritization of testing by the SMS. Nonetheless
      the dramatic increase in uptake demonstrates that DBS testing is acceptable to
      drug injectors and should be subject to more rigorous trials to evaluate its
      potential impact on diagnosis.

PMID- 19175880
TI  - Simian hepatitis A virus derived from a captive rhesus monkey in India is similar
      to the strain isolated from wild African green monkeys in Kenya.
AB  - SUMMARY: A simian hepatitis A virus (HAV) was identified retrospectively in a
      faecal sample from a rhesus monkey in India, inoculated in 1995 with a faecal
      suspension from a suspected patient of non-A to E hepatitis. The monkey was in
      captivity for 2 years in one of the experimental primate facilities in western
      India before being moved to the National Institute of Virology, Pune for
      experimentation. Phylogenetic analysis based on a partial sequence of the 5'
      noncoding region placed this virus in genotype V, the only other member being the
      AGM-27 strain recovered in 1986 from African green monkeys in Kenya. The source
      of infection of the monkey remains unclear. The full genome was amplified in nine
      fragments and sequenced. The genome of the Indian simian HAV (IND-SHAV) is 7425
      nucleotides long including the poly-A tail of 14 nucleotides at the 3' end. At
      the nucleotide and amino acid levels, IND-SHAV was 99.8 and 100% identical with
      AGM27, respectively.

PMID- 19175881
TI  - Epidemiology, course and disease burden of chronic hepatitis B virus infection.
      HEPNET study for chronic hepatitis B: a multicentre Greek study.
AB  - SUMMARY: Hepatitis B virus infection (HBV) has been recognized as a major health
      problem worldwide. Greece belongs to the intermediate endemicity countries with a
      trend of decreasing prevalence of HBV infection during the last decade. However,
      the recent massive immigration to our country may have led to alterations of HBV
      epidemiology. In this study, we evaluated the epidemiological features of HBV
      infection in a sample of 3480 patients followed up during the years 1997-2006.
      Immigrants mainly from Albania represented the 18.6% of the total study
      population and 56.6% of children. The majority of the patients had no family
      history of HBV infection (67.3%) or of acute hepatitis (95.4%), no known source
      of infection (64.6%), with intrafamilial spread accounting for 16.9% of the HBV
      transmission in adults and 33.9% in children. HBeAg(-) hepatitis B was the
      predominant form of hepatitis (92.1%) among the Greek patients in contrast to the
      immigrants where 16.6% were HBeAg(+). Liver cirrhosis was diagnosed in 8.8% of
      the total population and 0.9% had hepatocellular carcinoma. A high proportion of
      children were HBeAg(+) (62%), 55% from immigrant families, 25.2% were infected in
      the perinatal period and had no evidence of disease complications. In conclusion
      our results showed (a) a changing pattern in the epidemiology of HBV infection in
      Greece due to the significant number of HBeAg(+) patients, especially among
      children and (b) a considerable number of patients although aware of their
      infection, present with advanced disease.

PMID- 19175882
TI  - Intracellular levels of hepatitis B virus DNA and pregenomic RNA in peripheral
      blood mononuclear cells of chronically infected patients.
AB  - It remains uncertain whether hepatitis B virus (HBV) covalently closed circular
      DNA (cccDNA) and pregenomic RNA (pgRNA) can be detected in the serum or
      peripheral blood mononuclear cells (PBMC) of patients with chronic hepatitis B
      (CHB) infection. We examined HBV cccDNA and pgRNA in the serum and PBMC, and
      investigated the effect of lamivudine therapy on the viral loads in the PBMC of
      CHB patients. Paired serum and PBMC samples from 50 treatment-naive CHB patients
      [25 hepatitis B e antigen (HBeAg) positive and 25 HBeAg negative] were quantified
      for total HBV DNA, cccDNA and pgRNA by real time polymerase chain reaction. HBV
      cccDNA and pgRNA were below the lower detection limit in all serum samples, and
      in 84% of PBMC. HBV DNA (r = 0.889, P < 0.001) and pgRNA (r = 0.696, P < 0.001)
      in PBMC correlated with the HBV DNA in serum. In the longitudinal study, 30
      patients treated with lamivudine therapy for a median duration of 34 weeks (range
      12-48 weeks) were examined. The median HBV DNA reduction in PBMC before and after
      treatment was 1.318 (range -0.471 to 3.846) log units, which was significantly
      lower than serum HBV DNA reduction [3.371 (range -0.883 to 9.454) log units, P <
      0.05]. HBV cccDNA and pgRNA were undetectable in the serum of CHB patients. HBV
      viral loads in PBMC correlated with serum HBV DNA. Lamivudine therapy had less
      effect on the HBV viral loads in PBMC compared with the serum viral loads.

PMID- 19175883
TI  - On-treatment monitoring of adefovir therapy in chronic hepatitis B: virologic
      response can be assessed at 24 weeks.
AB  - Patients with chronic hepatitis B (CHB) who will and those who will not respond
      to adefovir (ADV) monotherapy need to be identified at an early stage in order to
      adjust treatment and prevent future development of antiviral resistance. In a
      single-centre cohort study, we investigated 76 CHB patients [50% hepatitis B e
      antigen (HBeAg)-positive] treated with long-term ADV monotherapy. During a median
      follow-up of 122 (24-185) weeks, 42 (55%) patients achieved virologic response
      (VR), defined as HBV-DNA levels <10(3) copies/mL, and 10 patients (13%) developed
      genotypic ADV resistance. Independent baseline predictors of VR were HBeAg
      negativity [hazard ratio (HR) 2.98; 95% confidence interval (CI) 1.24-7.19; P =
      0.02], high alanine aminotransferase (ALT) levels (HR 1.11; 95% CI 1.05-1.18; P =
      0.001), and low HBV-DNA levels (HR 0.56; 95% CI 0.41-0.75; P < 0.001). HBV-DNA at
      week 24 demonstrated a higher predictive value for VR than HBV-DNA at week 48.
      Important predictors of genotypic resistance were presence of cirrhosis (HR 6.54;
      95% CI 1.39-30.9; P = 0.018), and not achieving VR during treatment (HR 6.60; 95%
      CI 1.35-32.4; P = 0.008). Patients without VR at week 24 already demonstrated a
      trend towards the emergence of ADV resistance (P = 0.07). HBV-DNA at week 24 was
      a better on-treatment predictor of VR than HBV-DNA at week 48, and ADV-resistant
      mutations developed more frequently in patients without VR at week 24. Therefore,
      our study suggests that virologic response to ADV therapy can be assessed at 24
      weeks, instead of the generally recommended 48 weeks.

PMID- 19175884
TI  - Muscle relaxant use for tracheal intubation in pediatric anaesthesia: a survey of
      clinical practice in Germany.
AB  - OBJECTIVES: Aim of this Germany-wide study was to evaluate the use and
      application customs of neuromuscular blocking drugs (NMBDs) for tracheal
      intubation in children of age 5 years or younger. MATERIAL AND METHODS: In the
      year 2005, a total of 3260 questionnaires were sent out to all heads of
      anesthesia departments at all types of hospitals as well as ambulatory anesthesia
      centers in Germany. The fields covered by the questionnaire were regarding
      institutional size, amount of general anesthesia and specifically pediatric
      cases, number of intubations and NMBDs used, frequency of use of the individual
      relaxants and techniques utilized when administering muscle relaxants. RESULTS:
      Of the sent-out questionnaires 66.9% could be analyzed: 82% of hospitals use 1-3
      muscle relaxants in children; 91% of the ambulatory anesthesia centers use a
      repertoire of 1-2 neuromuscular blockers for pediatric cases. However, general
      anesthesia with tracheal intubation in children is often induced without using
      any NMBD at all. Mivacurium is the predominantly used NMBD for pediatric
      intubation in Germany. In contrast, the use of succinylcholine is far less in
      ambulatory anesthesia centers than in hospitals. Despite controversial
      discussion, precurarization, priming, and timing are still utilized in German
      anesthesia practice. CONCLUSION: In Germany, mivacurium, with its favorable
      pharmacologic profile for short cases, is the predominantly used NMBD for
      pediatric tracheal intubation. Despite the known adverse effects of intubation
      without muscle relaxation, this technique is also wide-spread, especially among
      German anesthetists in ambulatory anesthesia centers. Surveys like these are
      important to determine a status quo of use and application customs of NMBDs in
      pediatric anesthesia and provide a basis for numerous other studies.

PMID- 19175885
TI  - Experimental adaptation of the Enk oxygen flow modulator for potential pediatric
      use.
AB  - AIM: A bench study of the Enk oxygen flow modulator (Enk OFM) was conducted to
      test its performance and potential use in pediatric patients using the Advanced
      Paediatric Life Support (APLS) guidelines (Advanced Paediatric Life Support,
      2005: 224). BACKGROUND: The Enk OFM is a preassembled emergency transtracheal
      ventilation device. METHODS: The Enk OFM was connected to two sources of oxygen:
      first, to a Precision Medical flowmeter and second, to an Aestiva anesthetic
      machine axillary flowmeter. Testing was performed on standard cannulae of 20, 18,
      and 16 gauge caliber and also a 7.5 cm 15G Emergency Transtracheal Airway
      Catheter (Cook Medical). Serial hole occlusion of the Enk OFM was applied and the
      resulting flow rates were measured by a RespiCal Timeter. RESULTS: Oxygen flow
      was best controlled by occluding all holes of the Enk OFM and incrementally
      increasing oxygen flow by the flowmeter with an initial setting of 1 l min(-1)
      year(-1) of age. Contrary to the original description of this device (Anesth
      Analg 1998; 86: 203S), sequential occlusion of the five side holes does not lead
      to a significant exponential increase in gas flow. Incomplete occlusion of the
      Enk OFM provided insufficient and unpredictable flow. CONCLUSIONS: The Enk OFM
      should be fully occluded for inspiration with flow rates set at 1 l min(-1) year(
      1) of age and adjusted to effect. These flow rates are consistent with the APLS
      recommendations. Flows above 15 l min(-1) are potentially dangerous and the Enk
      OFM fails to perform as an on-off device. Flowmeter settings of <1 l min(-1) risk
      no flow. Cannulae of at least 18G should be used for optimal flow.

PMID- 19175887
TI  - ICOS-gene variants are not associated with atopic disease susceptibility in
      European children.
AB  - The inducible co-stimulatory molecule, ICOS, is an important regulator of T cell
      differentiation and effector function. Previously, it was reported that two
      variants in the ICOS promotor region, g.1-1413G>A and g.1-693G>A, were associated
      with sensitization to airborne allergens, elevated serum IgE levels and Th2
      cytokine production in a Hutterite population. The aim of this study was to
      evaluate these two and four other selected ICOS variants for association with
      atopic phenotypes in two large European prospective pediatric cohorts. We
      investigated subjects from the German Multicenter Allergy Study (MAS), which
      followed over 800 children with atopic family history from birth until 13 yr of
      age, and from the Early Treatment of the Allergic Child Study (ETAC), which
      collected DNA and clinical data of over 330 children with atopic dermatitis
      during their first 2 yr of life. We genotyped DNA from these children by melting
      curve analysis using fluorescence resonance energy transfer (FRET) probes. We
      could not confirm the previously reported association of g.1-1413G>A and g.1
      693G>A with atopic phenotypes in our pediatric cohorts. Also four other ICOS
      variants at putative binding sites for transcription factors showed no
      association with atopic dermatitis, asthma, allergic sensitization and allergic
      rhinitis. Our data suggest that these ICOS variants do not play a major role in
      the development of atopy in European children.

PMID- 19175888
TI  - The association of allergic symptoms with sensitization to inhalant allergens in
      childhood.
AB  - Although it is generally agreed that sensitization is an important risk factor
      for allergic diseases, the extent to which sensitization accounts for allergic
      symptoms in children is controversial. As part of the Aalst Allergy Study, this
      cross-sectional study investigated the prevalence of allergic symptoms and their
      association with sensitization in an unselected population of Flemish children
      aged 3.4-14.8 yr. Skin prick testing with the most common aeroallergens was
      performed and allergic symptoms were documented by a parental questionnaire. In
      the children older than 6 yr, a significant association of current wheezing,
      current dyspnea, airway hyperreactivity, rhinoconjunctivitis, and current eczema
      with sensitization was found, while in the pre-school children these associations
      were less pronounced. The association with sensitization was strongest for
      rhinoconjunctivitis and current respiratory symptoms - the association was less
      striking for children with current eczema. The impact of a positive family
      history of allergy on the association with sensitization was more important for
      eczema than for the other analyzed allergic symptoms. Persistent and late-onset
      wheezers were significantly more likely than non-wheezers and transient early
      wheezers to be associated with sensitization and a personal history of
      rhinoconjunctivitis. Late-onset wheezing was associated with a positive family
      history of allergy, while transient early wheezing was associated with day-care
      attendance. An association with eczema was found for all three childhood wheezing
      phenotypes. The association of allergic symptoms with sensitization is
      significant in the older but less pronounced in pre-school children and is more
      pronounced for current allergic symptoms. Diagnosis and disease definition of
      allergy symptoms remains difficult at pre-school age. The influence of a positive
      family history of allergy on the association of the respective allergic symptoms
      with sensitization was most important for eczema. Our data confirm the atopic
      characteristics of the different wheeze phenotypes.

PMID- 19175889
TI  - HPA axis safety of fluticasone furoate nasal spray once daily in children with
      perennial allergic rhinitis.
AB  - The effects of intranasal corticosteroids (INSs) on the hypothalamic-pituitary
      adrenal (HPA) axis should be assessed for any to be marketed INS. The objective
      of this study was to assess the effects of fluticasone furoate nasal spray (FFNS)
      on cortisol production (as a measure of HPA axis function) following 6 wk of
      treatment with FFNS 110 microg once daily (QD) compared with placebo in pediatric
      patients with perennial allergic rhinitis (PAR). In this double-blind, parallel
      group study, patients (n = 112) aged 2-11 yr with a 1-yr history of PAR (6 months
      for patients aged 2-3 yr) were randomized in a 1:1 ratio to either placebo or
      FFNS. Serum cortisol (SC) concentrations and urinary cortisol (UC) excretion were
      measured over a 24-h period at the randomization (baseline) and final treatment
      (week 6) visits for HPA axis evaluation in a domiciled environment (overnight in
      the clinic). Plasma samples were collected for FFNS at several time points over
      the 24 h after the final dose for pharmacokinetic analyses. FFNS was non-inferior
      to placebo with respect to change from baseline (expressed as a ratio) in 24-h SC
      weighted mean. The lower limit of the two-sided 95% confidence interval (CI) for
      the treatment ratio was greater than the pre-specified non-inferiority margin of
      0.8 (treatment ratio = 0.97, 95% CI 0.88-1.07). UC excretion over 24 h at
      baseline and end of treatment was similar between treatment groups; no patients
      had 24-h excretion levels below normal range after 6 wk of treatment. Plasma
      concentrations of FFNS were generally non-quantifiable (<10 pg/ml). Results of
      the current study indicate that FFNS 110 microg QD has no significant effect on
      HPA axis function in 2- to 11-yr-old pediatric patients with PAR.

PMID- 19175890
TI  - Cord blood cytokines and chemokines and development of allergic disease.
AB  - Exposure to ubiquitous allergens early in life, even before birth, may influence
      the incidence of allergic diseases later in life. During pregnancy, the
      fetomaternal interface is surrounded by high levels of T-helper (Th)2-like
      cytokines, possibly favouring the development of Th2-like immune responses in the
      offspring. The aim of this study was to evaluate the relation between cord blood
      (CB) IgE antibodies, Th1- and Th2-like cytokines and chemokines, maternal allergy
      and development of allergic disease during the first 2 yr of life in the
      offspring. The CB cytokine and chemokine levels from children of 20 allergic and
      36 non-allergic women were determined by a multiplexed Luminex assay and ELISA.
      Total CB and maternal IgE antibody concentrations were quantified using ImmunoCAP
      technology. The maternal IgE levels during and after pregnancy correlated with CB
      IgE and Th2-associated macrophage-derived chemokine [MDC (CCL22)] levels.
      Development of allergic disease and sensitization was associated with increased
      CB IgE and MDC (CCL22) levels, as well as high ratios of MDC (CCL22) to Th1
      associated interferon-gamma inducible protein 10 [IP-10 (CXCL10)] and interferon
      gamma inducible T-cell alpha-chemoattractant [I-TAC (CXCL11) (n = 7 allergic vs.
      n = 25 non-allergic)]. The correlations between maternal IgE and CB IgE and MDC
      (CCL22) levels possibly indicate that the maternal immunity can affect the
      Th1/Th2 profile in the neonate. Development of allergic disease is associated
      with a more marked Th2-like deviation already at birth, shown as increased levels
      of CB IgE and MDC (CCL22) and higher ratios of MDC (CCL22) to IP-10 (CXCL10) and
      I-TAC (CXCL11).

PMID- 19175891
TI  - The interaction between early life upper respiratory tract infection and birth
      during the pollen season on rye-sensitized hay fever and ryegrass sensitization-
      a birth cohort study.
AB  - Studies on early life viral respiratory infection and subsequent atopic disease
      in childhood have conflicting findings. Animal models show that viral respiratory
      infection in conjunction with allergen presentation can enhance sensitization.
      This prospective study assesses the influence of an upper respiratory tract
      infection (URI) in the first month of life and the season of birth on the
      development of hay fever and ryegrass allergen sensitization in childhood. From a
      Tasmanian cohort born during 1988 and 1989, a group of 498 children were followed
      up at 8 yr and another different group of 415 children were followed up at 16 yr.
      The ryegrass pollen season in Tasmania occurs in November and December. Forty
      four (9.6%) children in Follow-up sample 1 and 47 (12.5%) children in Follow-up
      sample 2 were born in the pollen season. The parental report of an early upper
      respiratory tract infection (EURI) was documented prospectively by a home
      interview at 1 month of age (median age 5.1 wk). Sensitization to ryegrass and
      house dust mite (HDM) was determined at 8 yr of age by skin prick testing and at
      16 yr by ImmunoCap. Ryegrass sensitized hay fever was defined as a positive
      response to a question on hay fever plus the presence of ryegrass allergy. For
      children tested at age 8 and born in the pollen season, a EURI by postnatal
      interview was associated with an increased risk of ryegrass sensitization (OR
      5.80 95% CI 1.07, 31.31) but not for children with a EURI born outside the pollen
      season (OR 0.62 95% CI 0.35, 1.08). Similarly, EURI was significantly associated
      with early onset (< or = 8 yr) ryegrass sensitized hay fever for children born in
      the pollen season (AOR 4.78 95% CI 1.17, 19.47) but was not associated with early
      onset ryegrass sensitized hay fever for children born outside the pollen season
      (AOR 0.76 95% CI 0.43, 1.33). These findings suggest that early life viral URI
      interacts with ryegrass allergen exposure in the development of ryegrass allergen
      sensitization and ryegrass sensitized hay fever symptoms.

PMID- 19175892
TI  - The comparison of cetirizine, levocetirizine and placebo for the treatment of
      childhood perennial allergic rhinitis.
AB  - Cetirizine (Zyrtec) is a potent and long-acting second-generation histamine H1-
      receptor antagonist for the treatment of allergic disease, such as allergic
      rhinitis and chronic idiopathic urticaria, in adult and child. It is a racemic
      mixture of levocetirizine (Xyzal) and dextrocetirizine. The purpose of this
      present study was to compare the efficacy of cetirizine, levocetirizine and
      placebo for the treatment of pediatric perennial allergic rhinitis. 74 perennial
      allergic rhinitis patients, aged 6 to 12 years old, assigned to 1 of 3 treatment
      groups for 12 weeks randomly. The effects of the three agents were compared with
      the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Total
      Symptom Score (TSS) by diary. Nasal peak expiratory flow rate (nPEFR) and
      laboratory examinations including serum immunoglobulin E level, eosinophil
      cationic protein (ECP), blood eosinophil counts and eosinophil percentage in a
      nasal smear were evaluated among the three groups. The results revealed that both
      cetirizine and levocetirizine improved TSS in comparison with the placebo group,
      and ceterizine appeared to be more efficacious than levocetirizine at week 8 and
      week 12. The PRQLQ score showed significant decreased both in cetirizine and
      levocetirizine group, but there was no statistic significant difference between
      both groups. The eosinophil proportion in a nasal smear significantly decreased
      among the cetirizine in comparison with the placebo group but there was no
      statistic significant in levocetirizine groups. Both cetirizine and
      levocetirizine showed significant improvement in nPEFR in comparison with the
      placebo group, and ceterizine appeared to be more efficacious than
      levocetirizine. The 12-week treatment program showed that cetirizine was more
      effectious than levocetirizine.

PMID- 19175893
TI  - Cytokine profiles in 1-yr-old very low-birth-weight infants after enteral
      glutamine supplementation in the neonatal period.
AB  - In a previous study, we found that glutamine-enriched enteral nutrition in 102
      very low-birth-weight (VLBW) infants decreased both the incidence of serious
      neonatal infections and atopic dermatitis during the first year of life. The aims
      of this follow-up study were to determine whether these beneficial effects are
      attended by changes in Th(1) and Th(2) cytokine profiles at age 1 yr.
      Furthermore, we studied changes in cytokine profiles during the first year of
      life in these VLBW infants. In total, 89 infants were eligible for the follow-up
      study (12 died, 1 exclusion due to a chromosomal abnormality). Th(1) (IFN-gamma,
      TNF- alpha and IL-2) and Th(2) cytokine (IL-10, IL-5, and IL-4) profiles
      following in vitro whole blood stimulation were measured at 1 yr. Cytokine
      profiles were measured in 59/89 (66%) infants. Glutamine-enriched enteral
      nutrition in neonatal period did not influence cytokine profiles at 1 yr.
      Cytokine profiles were not different in infants with and without allergic or
      infectious diseases. The beneficial effect of glutamine-enriched enteral
      nutrition on the incidence of serious neonatal infections and atopic dermatitis
      during the first year of life is not related to changes in the Th(1) and Th(2)
      cytokine profiles. Both Th(1) and Th(2) cytokine profiles increased during the
      first year of life in this cohort of VLBW infants.

PMID- 19175894
TI  - Waist circumference percentile thresholds for identifying adolescents with
      insulin resistance in clinical practice.
AB  - We formally evaluated waist circumference (WC) percentile cutoffs for predicting
      insulin resistance (IR) and whether different cutoffs should be used for
      adolescents of different race/ethnicities. Analysis was performed for 1575
      adolescents aged 12-18 yr from the National Health and Nutrition Examination
      Survey 1999-2002. Adolescents were classified as having IR if they had a
      homeostasis model assessment-insulin resistance level, a validated measure of IR,
      of >4.39, and WC percentile was classified according to previously published
      universal (all races combined) and race/ethnicity-specific WC percentile cutoffs.
      Receiver operating characteristic curves for predicting IR were constructed
      comparing the race/ethnicity-specific vs. universal WC percentile cutoffs, and
      area under the curve (AUC) was calculated. Comparing universal with
      race/ethnicity-specific WC percentiles, there were no significant differences in
      AUC for Black, Mexican-American, or White adolescents. Because race/ethnicity
      specific thresholds did not discriminate better than universal WC thresholds,
      universal WC thresholds may be used effectively to identify adolescents with IR
      in primary care practices. A WC > or =75th or > or =90th percentile for all
      race/ethnicities combined would be appropriate to apply in clinical practice for
      identification of adolescents with IR, a risk factor for development of type 2
      diabetes.

PMID- 19175895
TI  - Altered plasma adipokines and markers of oxidative stress suggest increased risk
      of cardiovascular disease in First Nation youth with obesity or type 2 diabetes
      mellitus.
AB  - OBJECTIVE: To evaluate cardiovascular disease risk in First Nation youth with and
      without type 2 diabetes mellitus (T2DM) or obesity by comparing pro- and anti
      inflammatory adipokines, markers of oxidative stress and the plasma phospholipid
      fatty acid profile. METHOD: Self-declared First Nation youth (12-15 yr) with T2DM
      (n = 24) as well as age-, gender-, and body mass index-matched controls (obese
      group; n = 19) and unmatched controls (control group; n = 34) were recruited from
      a pediatric diabetes clinic. RESULTS: Plasma tumor necrosis factor-alpha,
      ultrasensitive C-reactive protein, resistin, and total antioxidant status were
      not different among the three groups. Plasma total leptin, soluble leptin
      receptor, and free leptin were significantly higher in the T2DM group than the
      control group (p < 0.001, p = 0.019, p < 0.001, respectively) but did not differ
      from the obese group. Similarly, oxidized low-density lipoprotein was higher in
      the T2DM group compared with controls (p = 0.002) but not in the obese group.
      However, interleukin-6 was significantly higher (p < 0.001) in the T2DM group
      compared with both the control and the obese groups, suggesting that T2DM, but
      not an increase in adiposity, was responsible for this elevation. Adiponectin was
      significantly lower in the T2DM group compared with the control group only (p =
      0.035). CONCLUSIONS: Changes in plasma adipokines and oxidative stress can
      already be detected in youth with T2DM; however, many of the changes are mirrored
      in obese youth, suggesting that both these populations are at an increased risk
      for future cardiovascular complications.

PMID- 19175896
TI  - Diabetes summer camps: history, safety, and outcomes.

PMID- 19175897
TI  - Dermatological side effects and complications of continuous subcutaneous insulin
      infusion in preschool-age and school-age children.
AB  - OBJECTIVE: The objective of this study was to evaluate whether very young
      children develop more dermatological complications during insulin pump treatment
      compared with school children. STUDY DESIGN: Cross-sectional study in 78
      consecutive children using insulin pump treatment >4 months. RESULTS: Children in
      group A [n = 40, 28 males (M) and 12 females (F)] were 2.3 +/- 1.3 yr (+/-SD) and
      those in group B (n = 38, 13 M and 25 F) were 11.0 +/- 2.9 yr old at the start of
      continuous subcutaneous insulin infusion (CSII). The mean duration of CSII was
      similar in both groups (23.6 +/- 16.5 months in group A and 21.8 +/- 16.1 in
      group B). The most common dermatological complications were scars <3 mm (50% in
      group A vs. 71% in group B, p < 0.05) and lipohypertrophic areas at the insertion
      sites (45% in group vs. 47% in group B). Local abscesses and blisters were rare
      findings in both groups (7.5-12%), none leading to interruption or stop of CSII.
      CONCLUSIONS: Dermatological side effects during CSII are not more frequent or
      severe in very young diabetic children compared with diabetic children in school
      age.

PMID- 19175898
TI  - Missed bolus doses: devastating for metabolic control in CSII-treated adolescents
      with type 1 diabetes.
AB  - OBJECTIVE: To investigate the management of continuous subcutaneous insulin
      infusion (CSII) in adolescents with type 1 diabetes including their
      administration of bolus doses and to study relationships between insulin omission
      and metabolic control, body mass index, daily frequency of self-monitoring of
      blood glucose (SMBG) and bolus doses, health-related quality of life (HRQOL), the
      burden of diabetes and treatment satisfaction. METHODS: Ninety CSII-treated (> or
      =6 months) adolescents aged 12-18 yr, from four diabetes clinics in Sweden,
      participated in the study. The adolescents recorded their meal intake the
      previous day, which was compared with downloaded pump data, and the frequency of
      missed boluses was stated. Haemoglobin A1c (HbA1c) and diabetes-related data were
      recorded. HRQOL and treatment satisfaction were measured with questionnaires.
      RESULTS: Thirty-eight per cent of the adolescents had missed >15% of the doses
      the previous day, those had higher HbA1c (7.8 +/- 1.0 vs. 7.0 +/- 1.2%, p =
      0.001), took fewer daily boluses (3.8 +/- 1.7 vs. 5.3 +/- 1.7, p < 0.001) and
      SMBG (2.4 +/- 1.8 vs. 3.6 +/- 1.8, p = 0.003), were less satisfied with their
      treatment (4.8 vs. 5.3, scale 0-6, p = 0.029) and perceived the medical treatment
      more negatively (72.1 vs. 79.7, scale 0-100, p = 0.029). Multiple linear
      regression analysis showed that the variations in HbA1c could be explained by the
      frequency of bolus doses (p = 0.013) and SMBG per day (p < 0.0001) adjusted for
      duration and age (r(2) = 0.339, p < 0.0001). CONCLUSION: Insulin omission was
      common. Those who missed doses were less satisfied and perceived more impact with
      the treatment. The frequencies of daily boluses and SMBG were associated with
      metabolic control. Diabetes teams need strategies to guide adolescents on how to
      avoid insulin omission.

PMID- 19175900
TI  - Good glycemic control remains crucial in prevention of late diabetic
      complications--the Linkoping Diabetes Complications Study.
AB  - BACKGROUND: Several intervention studies have convincingly demonstrated the
      importance of good glycemic control to avoid long-term diabetic complications,
      but the importance of other risk factors remains controversial. We previously
      reported a markedly reduced incidence of severe retinopathy and nephropathy
      during the past decades in an unselected population of type 1 diabetes mellitus
      diagnosed in childhood. The aim of the present study was to analyze possible risk
      factors, which could explain the improved prognosis. METHODS: In this
      longitudinal population-based cohort study, we followed all 269 patients in whom
      type 1 diabetes mellitus was diagnosed in childhood 1961-1985 in a well-defined
      geographical area in Sweden. The patients were followed until the end of 1990 s.
      Multivariable regression models were used to analyze the importance of hemoglobin
      A1c (HbA(1c)), diabetes duration, blood pressure, cardiovascular risk factors and
      persisting C-peptide secretion for the development of diabetic retinopathy and
      nephropathy. RESULTS: Beside longer duration and higher HbA(1c), blood pressure
      and lipid values were higher and cardiovascular disease and smoking were more
      common in patients with severe complications. However, multivariable analysis
      abolished these associations. Diabetes duration and long-term HbA(1c) were the
      only significant independent risk factors for both retinopathy and nephropathy.
      The risk of overt nephropathy increased substantially when HbA(1c) was above 9.6%
      [Diabetes Control and Complications Trial (DCCT) corrected value], while the risk
      of severe retinopathy increased already when HbA(1c) exceeded 8.6%. CONCLUSION:
      In this unselected population, glycemic control was the only significant risk
      factor for the development of long-term complications.

PMID- 19175899
TI  - Prolonged use of continuous glucose monitors in children with type 1 diabetes on
      continuous subcutaneous insulin infusion or intensive multiple-daily injection
      therapy.
AB  - OBJECTIVE: For continuous glucose sensors to improve the treatment of children
      with type 1 diabetes (T1D), they must be accurate, comfortable to wear, and easy
      to use. We conducted a pilot study of the FreeStyle Navigator Continuous Glucose
      Monitoring System (Abbott Diabetes Care) to examine the feasibility of daily use
      of a continuous glucose monitor (CGM) in an extended ambulatory setting. METHODS:
      Following a 13-wk trial of daily Navigator use, 45 children with T1D [10.7 +/-
      3.7 yr, range 4.6-17.6, 24 using insulin pumps; continuous subcutaneous insulin
      infusion (CSII) and 21 using glargine-based multiple daily injections (MDI)] used
      the Navigator for an additional 13 wk. RESULTS: Navigator use was initially
      slightly higher in the CSII users than in the MDI users but declined similarly in
      both groups by 22-26 wk. After 26 wk, 11 (46%) of 24 CSII users and 7 (33%) of 21
      MDI users were using the CGM at least 5 d a week. No baseline demographic or
      clinical factors were predictive of the amount of sensor use at 26 wk. However,
      Navigator use during weeks 1-13 and scores on a CGM satisfaction survey at 13 wk
      were predictive of use in weeks 22-26. CONCLUSIONS: CGM was generally well
      tolerated in children with T1D for more than 6 months, and early acceptance of
      CGM was predictive of extended use of the device. Although many subjects and
      parents found CGM valuable, the declining usage over time underscores the need to
      develop new technologies and strategies to increase acceptance, effectiveness,
      and long-term use of these devices in youth with T1D.

PMID- 19175901
TI  - Improved metabolic outcome in a Danish diabetic paediatric population aged 0-18
      yr: results from a nationwide continuous Registration.
AB  - The objective of the present study was to describe the changes in glycaemic
      control based on data from the nationwide Danish Registry of Childhood Diabetes
      with valid haemoglobin A1c (HbA1c) readings centrally analysed between 1996 and
      2006. The glycaemic control was assessed using generalized linear mixed models.
      Centre, age, diabetes duration, ethnicity, sex, self-monitoring of blood glucose,
      insulin regimens and hypoglycaemia was tested as explanatory variables. There
      were 9291 HbA1c recordings from 2705 children with T1D during the 10-yr period.
      The unadjusted mean HbA1c value in 1997 was 9.05% (95% CI +/- 0.82) and in 2006
      was 8.20% (95% CI +/- 0.06). Mean HbA1c was significantly reduced over the years
      with a linear decrease of 0.08% per year (95% CI +/-0.011) (p < 0.0001). The
      decrease was unaffected by adjusting for number of injections, insulin/kg and use
      of insulin analogous. During the period, an increased frequency of self-monitored
      blood glucose was observed that was associated with a reduction in HbA1c (p <
      0.0001). The percentage of children with severe hypoglycaemia decreased from 12.2
      to 7.8% in those with HbA1c between 6 and 8%. Metabolic control in diabetic
      children has improved on a nationwide basis from the establishment of the
      national registry in 1996. The reduction in HbA1c was related to an increased
      number of self-monitoring of blood glucose values and a decrease in the number of
      hypoglycaemic events in those with the best metabolic control, whereas there were
      no association with the use of new analogous or insulin regimens.

PMID- 19175903
TI  - Diabetes mellitus, exocrine pancreatic deficiency, hypertrichosis,
      hyperpigmentation, and chronic inflammation: confirmation of a syndrome.
AB  - Type 1 diabetes mellitus is characterized by dysregulation of the immune system
      leading to inflammation and selective destruction of pancreatic beta cells. Mild
      to moderate pancreatic exocrine insufficiency is found in patients with type 1
      diabetes. Diabetes mellitus may also be part of a syndrome occasionally involving
      hair and skin abnormalities. We report our observations on two siblings with
      insulin-dependent diabetes, severe exocrine pancreatic deficiency, pigmented
      hypertrichotic skin patches with induration and chronic inflammation. The first
      sibling presented at the age of 9 months with hypertrichosis and
      hyperpigmentation, particularly on her back and legs and then developed diabetes
      mellitus at the age of 4 yr. The second sibling presented with exactly the same
      clinical features but at a later age of 12 yr. Both siblings had severe
      pancreatic exocrine deficiency with chronic persistent inflammation. Some of the
      clinical features in these siblings resemble those described by Prendiville et
      al. although our patients had additional features. The chronic inflammatory
      response in both siblings is highly suggestive of some form of immune
      dysregulation. The presence of consanguinity in the parents and similarity of
      clinical features in the siblings are suggestive of a novel autoimmune disorder,
      possibly secondary to autosomal recessive inheritance.

PMID- 19175902
TI  - Application of novel dual wave meal bolus and its impact on glycated hemoglobin
      A1c level in children with type 1 diabetes.
AB  - BACKGROUND: An insulin pump is an advanced technology offering new options of
      bolus - normal (N), dual wave (D-W) or square wave (S-W) bolus to deliver
      mealtime insulin. OBJECTIVES: To assess the impact of D-W/S-W boluses on
      metabolic control (glycated haemoglobin A1c, HbA1c) and to estimate the
      paediatric patients compliance with implementation of this system in daily
      practice. METHODS: The cross-sectional study included 499 records of patients
      aged 0-18 yr. Data from the insulin pump memory provided information on the
      number of D-W/S-W boluses during a 2-wk period, the insulin requirement (U/kg/d)
      and the percentage of basal insulin. The HbA1c value (%) and the patient's weight
      were determined during medical examinations. Mealtime dose of insulin in D-W/S-W
      bolus was calculated based on the amount of carbohydrate and fat/protein
      products. RESULTS: The number of applied D-W/S-W boluses was 16.6 +/- 0.77/14 d
      (ranged 0-95), while 18.8% of patients did not program D-W/S-W boluses. The
      lowest HbA1c value was found in the group using two and/or more D-W/S-W boluses
      per day (p = 0.001) compared with the group administrating less than one D-W/S-W
      bolus/d. Patients with HbA1c level <7.5% had a statistically higher relevant
      number of D-W/S-W boluses, 19.55 (95% CI: 17.44-21.65) vs. 12.42 (95% CI: 10.22
      14.61) (p < 0.001), while there was no correlation between the number of boluses
      and HbA1c in patients in the remission phase (<0.5 IU/kg/d) (r = 0.012, p =
      0.930). CONCLUSIONS: Patients using at least one D-W/S-W bolus per day achieved a
      recommended level of HbA1c. Paediatric patients with type 1 diabetes mellitus
      were found to be able to apply D-W/S-W boluses in daily self-treatment process
      based on food counting.

PMID- 19175904
TI  - Influence of food intake, age, gender, HbA1c, and BMI levels on plasma
      cholesterol in 29,979 children and adolescents with type 1 diabetes--reference
      data from the German diabetes documentation and quality management system (DPV).
AB  - OBJECTIVE: We investigated influences of a 12-h fast, age, gender, body mass
      index (BMI), hemoglobin A1c (HbA1c) on total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)
      to provide reference percentiles for TC, LDL-C, and HDL-C of patients with good
      diabetes control (HbA1c < 7.5%) and normal weight (BMI < 90th percentile).
      METHOD: A cross-sectional analysis of the diabetes documentation and quality
      management system using the diabetes data acquisition system for prospective
      surveillance (DPV) software included 29 979 patients with type 1 diabetes
      mellitus (T1DM) aged 1-20 yr (52.4% male) from 253 diabetes centers in Germany
      and Austria. RESULTS: Fasting had no relevant influence on TC, LDL-C, and HDL-C.
      Multivariate regression analysis revealed strongest dependences of cholesterol on
      gender and HbA1c followed by BMI and age. Reference cholesterol percentiles of
      well-controlled and normal weight patients showed TC >or=4.40 mmol/L (170 mg/dL)
      corresponding to the 50th percentile in females and the 75th percentile in males.
      LDL-C >or=2.59 mmol/L (100 mg/dL) corresponded to the 50th-75th percentile in
      females and the 75th percentile in males. CONCLUSIONS: (i) Fasting is no
      precondition for the determination of TC, LDL-C, and HDL-C; (ii) TC, LDL-C, and
      HDL-C are strongest associated with gender and HbA1c followed by BMI and age;
      (iii) Gender- and age-adjusted cholesterol percentiles of well-controlled and
      normal weight patients with T1DM may serve as reference values and are similar to
      healthy German children; and (iv) Single target values for TC, LDL-C, and HDL-C
      based on healthy individuals' data do not sufficiently characterize abnormal
      cholesterol levels in young patients with T1DM.

PMID- 19175905
TI  - "...because I am something special" or "I think I will be something like a guinea
      pig": information and assent of legal minors in clinical trials--assessment of
      understanding, appreciation and reasoning.
AB  - BACKGROUND: The aim of this study is to assess and evaluate the capacities for
      understanding, appreciation and reasoning of legal minors with psychiatric
      disorders and their parents and their competence to consent or assent to
      participation in clinical trials. The beliefs, fears, motivation and influencing
      factors for decision-making of legal minors and parents were also examined.
      METHODS: Using the MacArthur Competence Assessment Tool for Clinical Research
      (MacCAT-CR), an instrument developed for adults whose capacities to consent are
      unclear, we provided information about clinical trials and assessed
      understanding, appreciation and reasoning. We adapted this tool for legal minors
      and examined 19 children and adolescents between the ages of 7 and 15 with
      attention deficit/hyperactivity disorder (ADHD) or ADHD combined with
      oppositional defiant disorder (DSM-IV 314.00/314.01/312.8) enrolled in clinical
      trials. Parents were also examined using the MacCAT-CR. RESULTS: Facts such as
      the procedures involved in trials or their duration were well understood by legal
      minors, but more abstract issues like the primary purpose of the trial were not
      understood by children and adolescents or by many parents. Legal minors also had
      difficulties understanding the nature of placebo and the probability of receiving
      placebo. Children's and adolescents' decisions were influenced by fears about
      their disorder worsening and by problems in their relationship with their
      parents. Parents wanted the best therapy for their children in order to minimize
      problems in school. CONCLUSION: Legal minors and parents need to be informed more
      precisely about specific issues like placebo and the primary purpose of trials.
      In general, the reasoning of children and adolescents was influenced by their
      experience with their disorder and decision making was based on reasonable
      arguments. Their fears were based on everyday experiences such as school
      performance or family relationships.

PMID- 19175906
TI  - Extremely short duration high intensity interval training substantially improves
      insulin action in young healthy males.
AB  - BACKGROUND: Traditional high volume aerobic exercise training reduces
      cardiovascular and metabolic disease risk but involves a substantial time
      commitment. Extremely low volume high-intensity interval training (HIT) has
      recently been demonstrated to produce improvements to aerobic function, but it is
      unknown whether HIT has the capacity to improve insulin action and hence glycemic
      control. METHODS: Sixteen young men (age: 21 +/- 2 y; BMI: 23.7 +/- 3.1 kg x m-2;
      VO2peak: 48 +/- 9 ml x kg-1 x min-1) performed 2 weeks of supervised HIT
      comprising of a total of 15 min of exercise (6 sessions; 4-6 x 30-s cycle sprints
      per session). Aerobic performance (250-kJ self-paced cycling time trial), and
      glucose, insulin and NEFA responses to a 75-g oral glucose load (oral glucose
      tolerance test; OGTT) were determined before and after training. RESULTS:
      Following 2 weeks of HIT, the area under the plasma glucose, insulin and NEFA
      concentration-time curves were all reduced (12%, 37%, 26% respectively, all P <
      0.001). Fasting plasma insulin and glucose concentrations remained unchanged, but
      there was a tendency for reduced fasting plasma NEFA concentrations post-training
      (pre: 350 +/- 36 v post: 290 +/- 39 micromol x l-1, P = 0.058). Insulin
      sensitivity, as measured by the Cederholm index, was improved by 23% (P < 0.01),
      while aerobic cycling performance improved by approximately 6% (P < 0.01).
      CONCLUSION: The efficacy of a high intensity exercise protocol, involving only
      ~250 kcal of work each week, to substantially improve insulin action in young
      sedentary subjects is remarkable. This novel time-efficient training paradigm can
      be used as a strategy to reduce metabolic risk factors in young and middle aged
      sedentary populations who otherwise would not adhere to time consuming
      traditional aerobic exercise regimes.

PMID- 19175908
TI  - The association between RCAS1 expression in laryngeal and pharyngeal cancer and
      its healthy stroma with cancer relapse.
AB  - BACKGROUND: The purpose of this study has been to establish the level of RCAS1 -
      a membrane protein expressed in various cancer cells and able to induce apoptosis
      of CTLs and NK cells in pharyngeal and laryngeal cancer and its clear surgical
      margin - with respect to clinicopathological features and to patient's follow up
      and evaluate its possible role in cancer relapse. METHODS: A total of 122 tissue
      samples were obtained: 51 samples from laryngeal and pharyngeal squamous cell
      carcinoma, 51 samples from the clear surgical margins of these tumors, and 20
      tissue samples derived from the healthy mucous membranes of the upper respiratory
      tract mucosa of patients without cancerous tumors. Patients were observed for a
      total of 4 years following surgical treatment. The level of RCAS1 expression was
      assessed by immunohistochemistry and Western blot. RESULTS: RCAS1 was identified
      in all laryngeal and pharyngeal carcinomas and in almost all the clear surgical
      margin samples. The level of RCAS1 expression was significantly higher in the
      cancerous samples than in the clear surgical margins and was determined to be
      related to the grade of the cancer and the presence of lymph node metastases. In
      cases of cancer relapse, significantly higher levels of RCAS1 expression were
      observed in the clear surgical margins. CONCLUSION: Selective cytotoxic immune
      cell suppression concomitant with tumor growth and associated with RCAS1
      expression seems to be an important event connected with cancer relapse.

PMID- 19175909
TI  - Initiation of breastfeeding and prevalence of exclusive breastfeeding at hospital
      discharge in urban, suburban and rural areas of Zhejiang China.
AB  - BACKGROUND: Rates of exclusive breastfeeding in China are relatively low and
      below national targets. The aim of this study was to document the factors that
      influence exclusive breastfeeding initiation in Zhejiang, PR China. METHODS: A
      cohort study of infant feeding practices was undertaken in Zhejiang Province, an
      eastern coastal region of China. A total of 1520 mothers who delivered in four
      hospitals located in city, suburb and rural areas during late 2004 to 2005 were
      enrolled in the study. Multivariate logistic regression analysis was used to
      explore factors related to exclusive breastfeeding initiation. RESULTS: On
      discharge from hospital, 50.3% of the mothers were exclusively breastfeeding
      their infants out of 96.9% of the mothers who had earlier initiated
      breastfeeding. Exclusive breastfeeding was positively related to vaginal birth,
      baby's first feed being breast milk, mother living in the suburbs or rural areas,
      younger age of mother, lower maternal education level and family income.
      CONCLUSION: The exclusive breastfeeding rate in Zhejiang is only 50.3% on
      discharge and does not reach Chinese or international targets. A number of
      behaviours have been identified in the study that could be potentially
      incorporated into health promotion activities.

PMID- 19175910
TI  - Change in the direct cost of treatment for children and adolescents with
      hyperkinetic disorder in Germany over a period of four years.
AB  - BACKGROUND: In many developed countries, the treatment of hyperkinetic disorder
      (or ADHD) consumes a considerable amount of resources. The primary aim of this
      study was to determine change in the direct cost of treatment for children and
      adolescents with hyperkinetic disorder in Germany over time, and compare the cost
      with the cost of treatment for two physical disorders: epilepsy and asthma.
      METHODS: The German Federal Statistical Office provided data on the direct cost
      of treating hyperkinetic disorder, epilepsy and asthma in Germany for 2002, 2004,
      and 2006. The direct costs of treatment incurred by hyperkinetic disorder in
      these years were compared with those incurred by epilepsy and asthma. RESULTS:
      The total direct cost of treatment for the hyperkinetic disorder was euro 177
      million in 2002, euro 234 million in 2004, and euro 341 million in 2006. The
      largest proportion of the cost was incurred by the age group < 15 years: euro 158
      million in 2002, euro 205 million in 2004, and euro 287 million in 2006. The
      direct cost of treatment for epilepsy in this age group was a total of euro 157
      million in 2002, euro 155 million in 2004, and euro 155 million in 2006. For
      asthma, the total direct cost of treatment in this age group was euro 266 million
      in 2002, euro 257 million in 2004, and euro 272 million in 2006. CONCLUSION: The
      direct cost of treatment for hyperkinetic disorder in the age group < 15 years
      increased considerably between 2002 and 2006. Over the same period of time and
      for the same age group, expenditure for epilepsy and asthma was more or less
      constant. The increase in expenditure for the treatment of hyperkinetic disorder
      may be due to increasing demand for diagnostic and therapeutic services and
      improved availability of such services. The study is limited by the difficulty of
      obtaining consistent data on the direct cost of treatment for both physical and
      psychiatric disorders in Germany.

PMID- 19175912
TI  - Phenotypic and molecular characterization of Staphylococcus aureus isolates
      expressing low- and high-level mupirocin resistance in Nigeria and South Africa.
AB  - BACKGROUND: Mupirocin is a topical antimicrobial agent which is used for the
      treatment of skin and postoperative wound infections, and the prevention of nasal
      carriage of methicillin-resistant Staphylococcus aureus (MRSA). However, the
      prevalence of mupirocin resistance in S. aureus, particularly in MRSA, has
      increased with the extensive and widespread use of this agent in hospital
      settings. This study characterized low- and high-level mupirocin-resistant S.
      aureus isolates obtained from Nigeria and South Africa. METHODS: A total of 17
      mupirocin-resistant S. aureus isolates obtained from two previous studies in
      Nigeria and South Africa, were characterized by antibiogram, PCR-RFLP of the
      coagulase gene and PFGE. High-level mupirocin resistant isolates were confirmed
      by PCR detection of the mupA gene. The genetic location of the resistance
      determinants was established by curing and transfer experiments. RESULTS: All the
      low-level mupirocin resistant isolates were MRSA and resistant to gentamicin,
      tetracycline and trimethoprim. PFGE identified a major clone in two health care
      institutions located in Durban and a health care facility in Pietermaritzburg,
      Greytown and Empangeni. Curing and transfer experiments indicated that high-level
      mupirocin resistance was located on a 41.1 kb plasmid in the South African strain
      (A15). Furthermore, the transfer of high-level mupirocin resistance was
      demonstrated by the conjugative transfer of the 41.1 kb plasmid alone or with the
      co-transfer of a plasmid encoding resistance to cadmium. The size of the
      mupirocin-resistance encoding plasmid in the Nigerian strain (35 IBA) was
      approximately 35 kb. CONCLUSION: The emergence of mupirocin-resistant S. aureus
      isolates in Nigeria and South Africa should be of great concern to medical
      personnel in these countries. It is recommended that methicillin-susceptible S.
      aureus (MSSA) and MRSA should be routinely tested for mupirocin resistance even
      in facilities where the agent is not administered. Urgent measures, including
      judicious use of mupirocin, need to be taken to prevent clonal dissemination of
      the mupirocin/methicillin resistant S. aureus in KZN, South Africa and the
      transfer of the conjugative plasmid encoding high-level mupirocin resistance
      identified in this study.

PMID- 19175913
TI  - Exercise intolerance and systemic manifestations of pulmonary emphysema in a
      mouse model.
AB  - BACKGROUND: Systemic effects of chronic obstructive pulmonary disease (COPD)
      significantly contribute to severity and mortality of the disease. We aimed to
      develop a COPD/emphysema model exhibiting systemic manifestations of the disease.
      METHODS: Female NMRI mice were treated 5 times intratracheally with porcine
      pancreatic elastase (emphysema) or phosphate-buffered saline (control). Emphysema
      severity was quantified histologically by mean linear intercept, exercise
      tolerance by treadmill running distance, diaphragm dysfunction using isolated
      muscle strips, pulmonary hypertension by measuring right ventricular pressure,
      and neurohumoral activation by determining urinary norepinephrine concentration.
      RESULTS: Mean linear intercept was higher in emphysema (260.7 +/- 26.8 microm)
      than in control lungs (24.7 +/- 1.7 microm). Emphysema mice lost body weight,
      controls gained weight. Running distance was shorter in emphysema than in
      controls. Diaphragm muscle length was shorter in controls compared to emphysema.
      Fatigue tests of muscle strips revealed impaired relaxation in emphysema
      diaphragms. Maximum right ventricular pressure and norepinephrine were elevated
      in emphysema compared to controls. Linear correlations were observed between
      running distance changes and intercept, right ventricular weight, norepinephrine,
      and diaphragm length. CONCLUSION: The elastase mouse model exhibited severe
      emphysema with consecutive exercise limitation, and neurohumoral activation. The
      model may deepen our understanding of systemic aspects of COPD.

PMID- 19175914
TI  - Inappropriate prescribing and adverse drug events in older people.
AB  - Inappropriate prescribing (IP) in older patients is highly prevalent and is
      associated with an increased risk of adverse drug events (ADEs), morbidity,
      mortality and healthcare utilisation. Consequently, IP is a major safety concern
      and with changing population demographics, it is likely to become even more
      prevalent in the future. IP can be detected using explicit or implicit
      prescribing indicators. Theoretically, the routine clinical application of these
      IP criteria could represent an inexpensive and time efficient method to optimise
      prescribing practice. However, IP criteria must be sensitive, specific, have good
      inter-rater reliability and incorporate those medications most commonly
      associated with ADEs in older people. To be clinically relevant, use of
      prescribing appropriateness tools must translate into positive patient outcomes,
      such as reduced rates of ADEs. To accurately measure these outcomes, a reliable
      method of assessing the relationship between the administration of a drug and an
      adverse clinical event is required. The Naranjo criteria are the most widely used
      tool for assessing ADE causality, however, they are often difficult to interpret
      in the context of older patients. ADE causality criteria that allow for the
      multiple co-morbidities and prescribed medications in older people are required.
      Ultimately, the current high prevalence of IP and ADEs is unacceptable. IP
      screening criteria need to be tested as an intervention to assess their impact on
      the incidence of ADEs in vulnerable older patients. There is a role for IP
      screening tools in everyday clinical practice. These should enhance, not replace
      good clinical judgement, which in turn should be based on sound pharmacogeriatric
      training.

PMID- 19175915
TI  - Albumin dialysis improves hepatic encephalopathy and decreases circulating
      phenolic aromatic amino acids in patients with alcoholic hepatitis and severe
      liver failure.
AB  - INTRODUCTION: The aim of this study was to assess the effects of albumin dialysis
      on hepatic encephalopathy and circulating levels of amino acids in severe
      alcoholic hepatitis. METHODS: The study was carried out in nine patients with
      severe alcoholic hepatitis and four with primary biliary cirrhosis treated with
      the molecular adsorbent recirculating system. Besides standard liver function
      tests, circulating levels of ammonia, total, branched chain and aromatic amino
      acids, the presence and severity of hepatic encephalopathy, and number connection
      test were measured before and after each treatment. RESULTS: There were eight
      episodes of encephalopathy in patients with alcoholic hepatitis. Albumin dialysis
      was associated with significant improvement in encephalopathy (p = 0.02), and a
      decrease in total amino acid levels (2490 +/- 152 microM to 2229 +/- 114 microM,
      p < 0.001). Moreover, the Fischer's ratio, which was significantly lower in
      patients with alcoholic hepatitis (1.32 +/- 0.08) than in controls (3.20 +/-
      0.16), increased by 17% after albumin dialysis (p < 0.02) because of a
      significant decrease in phenolic aromatic amino acids (193 +/- 17 microM to 165
      +/- 9 microM, p = 0.04). No differences were observed in circulating ammonia.
      Changes in phenolic aromatic amino acids and the Fischer's ratio were more
      prominent in patients with encephalopathy and higher bilirubin removal. Albumin
      dialysis did not significantly affect the amino acid profile in the controls.
      CONCLUSIONS: Albumin dialysis results in a significant decrease in circulating
      phenolic aromatic amino acids and improvement of hepatic encephalopathy in
      patients with severe liver failure.

PMID- 19175916
TI  - Eukaryotic protein production in designed storage organelles.
AB  - BACKGROUND: Protein bodies (PBs) are natural endoplasmic reticulum (ER) or
      vacuole plant-derived organelles that stably accumulate large amounts of storage
      proteins in seeds. The proline-rich N-terminal domain derived from the maize
      storage protein gamma zein (Zera) is sufficient to induce PBs in non-seed tissues
      of Arabidopsis and tobacco. This Zera property opens up new routes for high-level
      accumulation of recombinant proteins by fusion of Zera with proteins of interest.
      In this work we extend the advantageous properties of plant seed PBs to
      recombinant protein production in useful non-plant eukaryotic hosts including
      cultured fungal, mammalian and insect cells. RESULTS: Various Zera fusions with
      fluorescent and therapeutic proteins accumulate in induced PB-like organelles in
      all eukaryotic systems tested: tobacco leaves, Trichoderma reesei, several
      mammalian cultured cells and Sf9 insect cells. This accumulation in membranous
      organelles insulates both recombinant protein and host from undesirable
      activities of either. Recombinant protein encapsulation in these PBs facilitates
      stable accumulation of proteins in a protected sub-cellular compartment which
      results in an enhancement of protein production without affecting the viability
      and development of stably transformed hosts. The induced PBs also retain the high
      density properties of native seed PBs which facilitate the recovery and
      purification of the recombinant proteins they contain. CONCLUSION: The Zera
      sequence provides an efficient and universal means to produce recombinant
      proteins by accumulation in ER-derived organelles. The remarkable cross-kingdom
      conservation of PB formation and their biophysical properties should have broad
      application in the manufacture of non-secreted recombinant proteins and suggests
      the existence of universal ER pathways for protein insulation.

PMID- 19175917
TI  - Chemokines are secreted by monocytes following OK-432 (lyophilized Streptococcus
      pyogenes) stimulation.
AB  - BACKGROUND: OK-432, penicillin-killed Streptococcus pyogenes, is used in treating
      lymphangiomas and carcinomas. We have studied in vitro the role of mononuclear
      phagocytes (MNPs), including purified monocytes (MOs), in the immune response to
      OK-432. MIP-1alpha/beta and MCP-1 secretions were assessed in whole blood (WB),
      peripheral blood mononuclear cells (PBMCs) and purified MOs, after in vitro
      stimulation with OK-432 with or without adherence for 24 hours. RESULTS: OK-432
      stimulated MNPs to secrete MCP-1 and MIP-1alpha/beta in healthy individuals and
      in head and neck squamous cell carcinoma (HNSCC) patients, except for OK-432
      stimulation of WB giving a minimal MIP-1alpha/beta response. Upon culture on low
      attachment wells, a spontaneous chemokine secretion was observed, with an
      unchanged secretion following OK-432 stimulation. Inhibition of Syk kinase and/or
      PI-3 kinase did not significantly change the chemokine response to OK-432, except
      for MIP-1alpha production being increased upon Syk inhibitor addition and an
      increased MCP-1 response upon addition of both inhibitors. Adhesion may possibly
      involve beta1 and/or beta3 integrins, not beta2, whereas beta(1-3) integrins may
      act as co-stimulatory receptors for OK-432. Based on direct blockage of CD36 or
      CD18 by antibodies, MCP-1 production may be mediated by CD18 while MIP-1beta and
      MCP-1 production may occur upon binding to CD36. CONCLUSION: Adherent human MOs
      produce MCP-1 and MIP-1alpha/beta upon stimulation with OK-432. CD36 modulates
      MIP-1beta and MCP-1 response. Thus, to some extent OK-432 acts as a substance
      whereby only MOs adhered to surfaces secrete MCP-1 and MIP-1alpha/beta, in part
      explaining why OK-432 is suited as a biological response modifying drug.

PMID- 19175918
TI  - Turkish version of impact on family scale: a study of reliability and validity.
AB  - BACKGROUND: Although there is a considerably high prevalence of developmental
      disorders in Turkey there are not many assessment tools related to evaluating the
      impact of these children on their family. The aim of this study was to determine
      the validity and reliability of the Turkish version of the Impact on Family Scale
      (IPFAM), a health related quality of life measurement to be utilized in clinical
      trials, health care services, research and evaluation. METHODS: Caregivers of 85
      children with developmental disabilities answered the questionnaire and 65 of
      them answered it twice with a one week interval. The reliability of the
      measurement was assessed by Cronbach's alpha coefficient, and with intraclass
      correlation coefficient (ICC) for test-retest reliability. Construct validity was
      assessed by calculating the correlation between total impact score of IPFAM,
      WeeFIM and the physiotherapists' evaluation via Visual Analogue Scale (VAS) to
      determine the child's disability. RESULTS: Test-retest reliability was found to
      be ICC = 0.953 for total impact, 0.843 for financial support, 0.940 for general
      impact, 0.871 for disruption of social relations and 0.787 for coping. Internal
      consistency was tested using Cronbach's alpha and was found to be 0.902 for total
      impact of IPFAM. For construct validity the correlation between total impact
      score of IPFAM and WeeFIM was r = -0,532 (p < 0.001) and the correlation between
      total impact score of IPFAM and the physiotherapist's evaluation was r = 0.519 (p
      < 0.001). CONCLUSION: The Turkish version of IPFAM was found to be a reliable and
      valid instrument for assessing the impact of developmental disorders of the child
      on the family.

PMID- 19175919
TI  - Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate
      in resistance trained men.
AB  - BACKGROUND: Dietary supplements targeting fat loss and increased thermogenesis
      are prevalent within the sport nutrition/weight loss market. While some isolated
      ingredients have been reported to be efficacious when used at high dosages, in
      particular in animal models and/or via intravenous delivery, little objective
      evidence is available pertaining to the efficacy of a finished product taken by
      human subjects in oral form. Moreover, many ingredients function as stimulants,
      leading to increased hemodynamic responses. The purpose of this investigation was
      to determine the effects of a finished dietary supplement on plasma catecholamine
      concentration, markers of lipolysis, metabolic rate, and hemodynamics. METHODS:
      Ten resistance trained men (age = 27 +/- 4 yrs; BMI = 25 +/- 3 kg. m-2; body fat
      = 9 +/- 3%; mean +/- SD) ingested a dietary supplement (Meltdown(R), Vital
      Pharmaceuticals) or a placebo, in a random order, double blind cross-over design,
      with one week separating conditions. Fasting blood samples were collected before,
      and at 30, 60, and 90 minutes post ingestion and were assayed for epinephrine
      (EPI), norepinephrine (NE), glycerol, and free fatty acids (FFA). Area under the
      curve (AUC) was calculated for all variables. Gas samples were collected from 30
      60 minutes post ingestion for measurement of metabolic rate. Heart rate and blood
      pressure were recorded at all blood collection times. RESULTS: AUC was greater
      for the dietary supplement compared to the placebo for NE (1332 +/- 128 pg.mL
      1.90 min-1 vs. 1003 +/- 133 pg.mL-1.90 min-1; p = 0.03), glycerol (44 +/- 3
      mug.mL-1.90 min-1 vs. 26 +/- 2 mug.mL-1.90 min-1; p < 0.0001), and FFA (1.24 +/-
      0.17 mmol.L-1.90 min-1 vs. 0.88 +/- 0.12 mmol.L-1.90 min-1; p = 0.0003). No
      difference between conditions was noted for EPI AUC (p > 0.05). For all
      variables, values were highest at 90 minutes post ingestion. Total kilocalorie
      expenditure during the 30 minute collection period was 29.6% greater (p = 0.02)
      for the dietary supplement (35 +/- 3 kcal) compared to placebo (27 +/- 2 kcal). A
      condition main effect was noted for systolic blood pressure (p = 0.04), with
      values increasing from 117 +/- 2 mmHg to 123 +/- 2 mmHg with the dietary
      supplement, while remaining unchanged for placebo. No other hemodynamic changes
      were noted (p > 0.05). CONCLUSION: The dietary supplement results in an acute
      increase in plasma NE and markers of lipolysis, as well as metabolic rate. This
      occurs without altering hemodynamic variables in a clinically significant manner.
      Intervention studies to determine the impact of this dietary supplement on
      weight/fat loss are warranted.

PMID- 19175921
TI  - A clinical registry of dementia based on the principle of epidemiological
      surveillance.
AB  - BACKGROUND: Traditional epidemiological studies do not allow elucidating the
      reality of referral and diagnosis patterns of dementia in routine clinical
      practice within a defined territory. This information is useful and necessary in
      order to plan and allocate healthcare resources. This paper presents the results
      from a dementia case registry based on epidemiological surveillance fundamentals.
      METHODS: Standardised registry of dementia diagnoses made in 2007 by specialised
      care centres in the Health Region of Girona (RSG) (Spain), which encompasses an
      area of 5,517 sq. km and a reference population of 690,207 inhabitants. RESULTS:
      577 cases of dementia were registered, of which 60.7% corresponded to cases of
      Alzheimer's disease. Presenile dementia accounted for 9.3% of the cases. Mean
      time between the onset of symptoms and clinical diagnosis was 2.4 years and the
      severity of the dementia was mild in 60.7% of the cases. High blood pressure, a
      family history of dementia, dislipidemia, and a past history of depression were
      the most common conditions prior to the onset of the disease (>20%). CONCLUSION:
      The ReDeGi is a viable epidemiological surveillance device that provides
      information about the clinical and demographic characteristics of patients
      diagnosed with dementia in a defined geographical area.

PMID- 19175922
TI  - Construction of 12 EST libraries and characterization of a 12,226 EST dataset for
      chicory (Cichorium intybus) root, leaves and nodules in the context of
      carbohydrate metabolism investigation.
AB  - BACKGROUND: The industrial chicory, Cichorium intybus, is a member of the
      Asteraceae family that accumulates fructan of the inulin type in its root. Inulin
      is a low calories sweetener, a texture agent and a health promoting ingredient
      due to its prebiotic properties. Average inulin chain length is a critical
      parameter that is genotype and temperature dependent. In the context of the study
      of carbohydrate metabolism and to get insight into the transcriptome of chicory
      root and to visualize temporal changes of gene expression during the growing
      season, we obtained and characterized 10 cDNA libraries from chicory roots
      regularly sampled in field during a growing season. A leaf and a nodule libraries
      were also obtained for comparison. RESULTS: Approximately 1,000 Expressed
      Sequence Tags (EST) were obtained from each of twelve cDNA libraries resulting in
      a 12,226 EST dataset. Clustering of these ESTs returned 1,922 contigs and 4,869
      singlets for a total of 6,791 putative unigenes. All ESTs were compared to public
      sequence databases and functionally classified. Data were specifically searched
      for sequences related to carbohydrate metabolism. Season wide evolution of
      functional classes was evaluated by comparing libraries at the level of
      functional categories and unigenes distribution. CONCLUSION: This chicory EST
      dataset provides a season wide outlook of the genes expressed in the root and to
      a minor extent in leaves and nodules. The dataset contains more than 200
      sequences related to carbohydrate metabolism and 3,500 new ESTs when compared to
      other recently released chicory EST datasets, probably because of the season wide
      coverage of the root samples. We believe that these sequences will contribute to
      accelerate research and breeding of the industrial chicory as well as of closely
      related species.

PMID- 19175920
TI  - Evidence for niche adaptation in the genome of the bovine pathogen Streptococcus
      uberis.
AB  - BACKGROUND: Streptococcus uberis, a Gram positive bacterial pathogen responsible
      for a significant proportion of bovine mastitis in commercial dairy herds,
      colonises multiple body sites of the cow including the gut, genital tract and
      mammary gland. Comparative analysis of the complete genome sequence of S. uberis
      strain 0140J was undertaken to help elucidate the biology of this effective
      bovine pathogen. RESULTS: The genome revealed 1,825 predicted coding sequences
      (CDSs) of which 62 were identified as pseudogenes or gene fragments. Comparisons
      with related pyogenic streptococci identified a conserved core (40%) of
      orthologous CDSs. Intriguingly, S. uberis 0140J displayed a lower number of
      mobile genetic elements when compared with other pyogenic streptococci, however
      bacteriophage-derived islands and a putative genomic island were identified.
      Comparative genomics analysis revealed most similarity to the genomes of
      Streptococcus agalactiae and Streptococcus equi subsp. zooepidemicus. In
      contrast, streptococcal orthologs were not identified for 11% of the CDSs,
      indicating either unique retention of ancestral sequence, or acquisition of
      sequence from alternative sources. Functions including transport, catabolism,
      regulation and CDSs encoding cell envelope proteins were over-represented in this
      unique gene set; a limited array of putative virulence CDSs were identified.
      CONCLUSION: S. uberis utilises nutritional flexibility derived from a diversity
      of metabolic options to successfully occupy a discrete ecological niche. The
      features observed in S. uberis are strongly suggestive of an opportunistic
      pathogen adapted to challenging and changing environmental parameters.

PMID- 19175923
TI  - Oral cancer awareness amongst hospital nursing staff: a pilot study.
AB  - BACKGROUND: Oral cancer is as prevalent as cervical and testicular cancer in the
      United Kingdom. Nursing staff provide the oral health care for the patient
      population in hospital. Admission to hospital provides a 'window of opportunity'
      for oral cancer 'screening' via an oral health check during nursing clerking.
      This study aimed to investigate whether nursing staff are aware of risk factors
      for oral cancer, its clinical signs, and could therefore provide a 'screening'
      service for oral cancer. METHOD: Through the use of a questionnaire we assessed
      121 nursing staff on oral health check behaviour and attitudes; their knowledge
      of risk factors for oral cancer; their understanding of common clinical signs of
      oral cancer; and their undergraduate and postgraduate training in oral health and
      oral cancer. RESULTS: Over 80% thought oral health checks were important although
      only 49% performed this task regularly; approximately 70% identified smoking as a
      risk factor but less than 30% identified alcohol. Awareness of the clinical signs
      of oral cancer was low with 21% identifying white patches, 15% identifying
      ulceration and only 2% identifying red patches despite their malignant potential.
      Nurses within 3 years of qualification were significantly better at recognising
      risk factors for oral cancer than their colleagues, identifying a need for
      continuing postgraduate education on oral health and oral cancer. Sixty-one
      percent of nursing staff received oral healthcare as an undergraduate with 34
      percent receiving postgraduate training. CONCLUSION: An oral health check upon
      admission to hospital provides an opportunity for nurses to 'screen' for oral
      diseases including oral cancer and allows nurses a greater role in total patient
      care. Nurses' awareness of oral cancer risk factors and clinical signs was,
      however, poor. This study highlights a need for improved education of nurses on
      oral cancer to make the oral health check on admission viable for oral cancer
      screening.

PMID- 19175924
TI  - Infarction of middle third posterior cortex of kidney: a complication of extended
      pyelolithotomy, intra-operative electrohydraulic lithotripsy and extraction of
      calyceal stones under vision using stone basket and flexible cystoscope in a
      spinal cord injury patient - a case report.
AB  - BACKGROUND: Spinal cord injury produces multiple systemic and metabolic
      alterations. A decrease in micro vascular blood flow to liver, spleen and muscle
      has been described following spinal cord injury. CASE PRESENTATION: We present a
      46-year-old male patient with C-4 complete tetraplegia, who developed a large
      stag horn calculus with branches in upper, middle and lower calyces of left
      kidney. This patient underwent Gil-Vernet extended pyelolithotomy and required
      intra-operative electrohydraulic lithotripsy and retrieval of stones from upper,
      middle and lower calyces using flexible cystoscope and stone basket. Computed
      tomography, performed eighteen days after surgery, showed multiple areas of non
      enhancing cortex posteriorly and in the upper pole, suggestive of focal
      infarction. Magnetic resonance imaging of left kidney confirmed the presence of
      an area of infarction in middle third of posterior cortex, but there was no
      evidence of trauma to posterior division of renal artery. Therefore, we postulate
      that compression of renal parenchyma by Gil-Vernet retractors during surgery, and
      firm pressure that was applied over the middle of kidney for prolonged periods
      while several attempts were being made to retrieve fragments of calculi from
      renal calyces, led to ischaemia and subsequently, infarction of mid-third
      posterior cortex of left kidney. CONCLUSION: This case illustrates importance of
      gentle handling of kidney during extended pyelolithotomy in order to prevent
      subtle renal trauma, which may be detected only by advanced imaging studies.
      Further, spinal cord physicians should take a pragmatic approach to management of
      stones located inside renal calyces. Both spinal cord injury patients and their
      physicians should remember that in our enthusiasm to achieve complete clearance
      of stones embedded deeply within renal calyces, we could produce irreversible
      injury to kidney, as indeed happened in this patient. Therefore, emphasis should
      be placed on prevention of struvite renal calculi by discarding indwelling
      urinary catheters and eliminating Proteus bacteriuria.

PMID- 19175925
TI  - Establishing the added benefit of measuring MMP9 in FOB positive patients as a
      part of the Wolverhampton colorectal cancer screening programme.
AB  - BACKGROUND: Bowel cancer is common and a major cause of death. The NHS is
      currently rolling out a national bowel cancer screening programme that aims to
      cover the entire population by 2010. The programme will be based on the Faecal
      Occult Blood test (FOBt) that reduces mortality from colon cancer by 16%.
      However, FOB testing has a relatively low positive predictive value, with
      associated unnecessary cost, risk and anxiety from subsequent investigation, and
      is unacceptable to a proportion of the target population. Increased levels of an
      enzyme called matrix metalloproteinase 9 (MMP9) have been found to be associated
      with colorectal cancer, and this can be measured from a blood sample. MMP9 has
      potential for detecting those at risk of having colorectal cancer. The aim of
      this study is to assess whether MMP9 estimation enhances the predictive value of
      a positive FOBt. METHODS AND DESIGN: FOBt positive people aged 60-69 years
      attending the Wolverhampton NHS Bowel Cancer Screening Unit and providing consent
      for colonoscopy will be recruited. Participants will provide a blood sample prior
      to colonoscopy and permission for collection of the clinical outcome from
      screening unit records. Multivariate logistic regression analyses will determine
      the independent factors (patient and disease related, MMP9) associated with the
      prediction of neoplasia. DISCUSSION: Colorectal cancer is a major cause of
      morbidity and mortality. Pilot studies have confirmed the feasibility of the
      national cancer screening programme that is based on FOBt. However, the test has
      high false positive rates. MMP9 has significant potential as a marker for both
      adenomas and cancers. This study is to examine whether using MMP9 as an adjunct
      to FOBt improves the accuracy of screening and reduces the number of false
      positive tests that cause anxiety and require invasive and potentially harmful
      investigation.

PMID- 19175927
TI  - Genome-scale constraint-based modeling of Geobacter metallireducens.
AB  - BACKGROUND: Geobacter metallireducens was the first organism that can be grown in
      pure culture to completely oxidize organic compounds with Fe(III) oxide serving
      as electron acceptor. Geobacter species, including G. sulfurreducens and G.
      metallireducens, are used for bioremediation and electricity generation from
      waste organic matter and renewable biomass. The constraint-based modeling
      approach enables the development of genome-scale in silico models that can
      predict the behavior of complex biological systems and their responses to the
      environments. Such a modeling approach was applied to provide physiological and
      ecological insights on the metabolism of G. metallireducens. RESULTS: The genome
      scale metabolic model of G. metallireducens was constructed to include 747 genes
      and 697 reactions. Compared to the G. sulfurreducens model, the G.
      metallireducens metabolic model contains 118 unique reactions that reflect many
      of G. metallireducens' specific metabolic capabilities. Detailed examination of
      the G. metallireducens model suggests that its central metabolism contains
      several energy-inefficient reactions that are not present in the G.
      sulfurreducens model. Experimental biomass yield of G. metallireducens growing on
      pyruvate was lower than the predicted optimal biomass yield. Microarray data of
      G. metallireducens growing with benzoate and acetate indicated that genes
      encoding these energy-inefficient reactions were up-regulated by benzoate. These
      results suggested that the energy-inefficient reactions were likely turned off
      during G. metallireducens growth with acetate for optimal biomass yield, but were
      up-regulated during growth with complex electron donors such as benzoate for
      rapid energy generation. Furthermore, several computational modeling approaches
      were applied to accelerate G. metallireducens research. For example, growth of G.
      metallireducens with different electron donors and electron acceptors were
      studied using the genome-scale metabolic model, which provided a fast and cost
      effective way to understand the metabolism of G. metallireducens. CONCLUSION: We
      have developed a genome-scale metabolic model for G. metallireducens that
      features both metabolic similarities and differences to the published model for
      its close relative, G. sulfurreducens. Together these metabolic models provide an
      important resource for improving strategies on bioremediation and bioenergy
      generation.

PMID- 19175926
TI  - Microvolt T-wave alternans as a predictor of mortality and severe arrhythmias in
      patients with left-ventricular dysfunction: a systematic review and meta
      analysis.
AB  - BACKGROUND: Studies have demonstrated that the use of implantable cardioverter
      defibrillators (ICDs) is effective for the primary prevention of arrhythmic
      events but due to imposing costs, there remains a need to identify which patients
      will derive the greatest benefit. Microvolt T-wave alternans (MTWA) has been
      proposed to assist in this stratification. METHODS: We systematically searched
      the literature using MEDLINE, EMBASE, Current Contents, the Cochrane Library,
      INAHTA, and the Web of Science to identify all primary prevention randomized
      controlled trials and prospective cohort studies with at least 12 months of
      follow-up examining MTWA as a predictor of mortality and severe arrhythmic events
      in patients with severe left-ventricular dysfunction. The search was limited to
      full-text English publications between January 1990 and May 2007. The primary
      outcome was a composite of mortality and severe arrhythmias. Data were
      synthesized using Bayesian hierarchical models. RESULTS: We identified no trials
      and 8 published cohort studies involving a total of 1,946 patients, including 332
      positive, 656 negative, 84 indeterminate, and 874 non-negative (which includes
      both positive and indeterminate tests) MTWA test results. The risk of mortality
      or severe arrhythmic events was higher in patients with a positive MTWA compared
      to a negative test (RR = 2.7, 95% credible interval (CrI) = 1.4, 6.1). Similar
      results were obtained when comparing non-negative MTWA to a negative test.
      CONCLUSION: A positive MTWA test predicts mortality or severe arrhythmic events
      in a population of individuals with severe left ventricular dysfunction. However,
      the wide credible interval suggests the clinical utility of this test remains
      incompletely defined, ranging from very modest to substantial. Additional high
      quality studies are required to better refine the role of MTWA in the decision
      making process for ICD implantation.

PMID- 19175928
TI  - Summary of the primer on tumor immunology and the biological therapy of cancer.
AB  - The International Society for Biological Therapy of Cancer (iSBTc) is one of the
      "premier destinations for interaction and innovation in the cancer biologics
      community". It provides a primer course each year during the annual meeting to
      address the most important areas of tumor immunology and immunotherapy. The
      course has been given by prominent investigators in the area of interest,
      covering the core principles of cancer immunology and immunotherapy. The target
      audience for this program includes investigators from academic, regulatory, and
      biopharmaceutical venues. The program goal is to enable the attendees to learn
      the current status and the most recent advances in biologic therapies, and to
      leverage this knowledge towards the improvement of cancer therapy. The 2008
      immunologic primer course was held on October 30 at the 23rd Annual meeting of
      iSBTc in San Diego, CA. Nine internationally renowned investigators gave
      excellent presentations on different topics. The topics covered in this primer
      included: (1) cytokines in cancer immunology; (2) anti-angiogenic therapy; (3)
      end stage: immune killing of tumors; (4) blocking T cell checkpoints; (5)
      approach to identification and therapeutic exploitation of tumor antigens; (6) T
      regulatory cells; (7) adoptive T cell therapy; (8) immune monitoring of cancer
      immunotherapy; and (9) immune adjuvants. We summarized the topics in this primer
      for public education. The related topic slides and schedule can be accessed
      online http://www.isbtc.org/meetings/am08/primer08.

PMID- 19175930
TI  - Oculopharyngeal muscular dystrophy as a rare differential diagnosis for
      unexplained dysphagia: a case report.
AB  - INTRODUCTION: We wish to report on a rare cause of dysphagia; oculopharyngeal
      muscular dystrophy (OPMD). It is a late adult onset autosomal dominant form of
      muscular dystrophy that constitutes as a rare diagnosis for any place outside of
      Canada and first case in southern Germany. CASE PRESENTATION: We report the
      medical odyssey of a 57-year old male Caucasian patient. He was referred at our
      hospital for further clarification of a progressive dysphagia, which, at first
      view, was thought to be tumor related due to the patient's typical anamnesis.
      CONCLUSION: The present report outlines the importance of considering this rare
      disease for general medicine practitioners as well as head and neck specialists
      as a differential diagnosis for swallowing disorders with, even at second view,
      uncertain cause.

PMID- 19175929
TI  - A glycosylated recombinant human granulocyte colony stimulating factor produced
      in a novel protein production system (AVI-014) in healthy subjects: a first-in
      human, single dose, controlled study.
AB  - BACKGROUND: AVI-014 is an egg white-derived, recombinant, human granulocyte
      colony-stimulating factor (G-CSF). This healthy volunteer study is the first
      human investigation of AVI-014. METHODS: 24 male and female subjects received a
      single subcutaneous injection of AVI-014 at 4 or 8 mcg/kg. 16 control subjects
      received 4 or 8 mcg/kg of filgrastim (Neupogen, Amgen) in a partially blinded,
      parallel fashion. RESULTS: The Geometric Mean Ratio (GMR) (90% CI) of 4 mcg/kg
      AVI-014/filgrastim AUC(0-72 hr) was 1.00 (0.76, 1.31) and Cmax was 0.86 (0.66,
      1.13). At the 8 mcg/kg dose, the AUC(0-72) GMR was 0.89 (0.69, 1.14) and Cmax was
      0.76 (0.58, 0.98). A priori pharmacokinetic bioequivalence was defined as the 90%
      CI of the GMR bounded by 0.8-1.25. Both the white blood cell and absolute
      neutrophil count area under the % increase curve AUC(0-9 days) and Cmax (maximal
      % increase from baseline)GMR at 4 and 8 mcg/kg fell within the 0.5-2.0 a priori
      bound set for pharmacodynamic bioequivalence. The CD 34+ % increase curve AUC(0-9
      days) and Cmax GMR for both doses was approximately 1, but 90% confidence
      intervals were large due to inherent variance, and this measure did not meet
      pharmacodynamic bioequivalence. AVI-014 demonstrated a side effect profile
      similar to that of filgrastim. CONCLUSION: AVI-014 has safety, pharmacokinetic,
      and pharmacodynamic properties comparable to filgrastim at an equal dose in
      healthy volunteers. These findings support further investigation in AVI-014.

PMID- 19175931
TI  - Use of anabolic-androgenic steroids masking the diagnosis of pleural
      tuberculosis: a case report.
AB  - INTRODUCTION: Tuberculous pleural effusions are not always easy to diagnose but
      the presence of a lymphocyte-rich exudate associated with an increased adenosine
      deaminase level and a positive skin test result are highly sensitive diagnostic
      signs. CASE PRESENTATION: We report a case of pleural tuberculosis in a 31-year
      old white male patient from Caracas, Venezuela who was negative for human
      immunodeficiency virus and presented 2 weeks after injecting the anabolic
      androgenic steroid nandrolone decanoate, in whom all the tests for tuberculosis
      were initially negative; an eosinophilic pleural effusion with a low adenosine
      deaminase level, a negative tuberculin skin test and negative for acid-fast
      bacilli staining and culture of the pleural fluid. After excluding other causes
      of eosinophilic pleural effusion malignant pleural effusion was suspected. The
      patient did not return until 4 months later. The second thoracentesis obtained a
      pleural fluid suggestive for tuberculosis, with a predominance of lymphocytes, an
      elevated adenosine deaminase level (51 U/l) and a positive tuberculin skin test.
      Culture of pleural fragments confirmed pleural tuberculosis. CONCLUSION: This
      case suggests that the use of an anabolic-androgenic steroid masks the definitive
      diagnosis of pleural tuberculosis by changing the key diagnostic parameters of
      the pleural fluid, a finding not previously reported. Available evidence of the
      effects of anabolic steroids on the immune system also suggests that patients
      using anabolic-androgenic steroids might be susceptible to developing
      tuberculosis in either reactivating a latent infection or facilitating
      development of the disease after a recent infection.

PMID- 19175932
TI  - Bioelectrical impedance phase angle in clinical practice: implications for
      prognosis in stage IIIB and IV non-small cell lung cancer.
AB  - BACKGROUND: A frequent manifestation of advanced lung cancer is malnutrition,
      timely identification and treatment of which can lead to improved patient
      outcomes. Bioelectrical impedance analysis (BIA) is an easy-to-use and non
      invasive technique to evaluate changes in body composition and nutritional
      status. We investigated the prognostic role of BIA-derived phase angle in
      advanced non-small cell lung cancer (NSCLC). METHODS: A case series of 165 stages
      IIIB and IV NSCLC patients treated at our center. The Kaplan Meier method was
      used to calculate survival. Cox proportional hazard models were constructed to
      evaluate the prognostic effect of phase angle, independent of stage at diagnosis
      and prior treatment history. RESULTS: 93 were males and 72 females. 61 had stage
      IIIB disease at diagnosis while 104 had stage IV. The median phase angle was 5.3
      degrees (range = 2.9 - 8). Patients with phase angle <or= 5.3 had a median
      survival of 7.6 months (95% CI: 4.7 to 9.5; n = 81), while those with > 5.3 had
      12.4 months (95% CI: 10.5 to 18.7; n = 84); (p = 0.02). After adjusting for age,
      stage at diagnosis and prior treatment history we found that every one degree
      increase in phase angle was associated with a relative risk of 0.79 (95% CI: 0.64
      to 0.97, P = 0.02). CONCLUSION: We found BIA-derived phase angle to be an
      independent prognostic indicator in patients with stage IIIB and IV NSCLC.
      Nutritional interventions targeted at improving phase angle could potentially
      lead to an improved survival in patients with advanced NSCLC.

PMID- 19175933
TI  - Analyses of zebrafish and Xenopus oocyte maturation reveal conserved and diverged
      features of translational regulation of maternal cyclin B1 mRNA.
AB  - BACKGROUND: Vertebrate development relies on the regulated translation of stored
      maternal mRNAs, but how these regulatory mechanisms may have evolved to control
      translational efficiency of individual mRNAs is poorly understood. We compared
      the translational regulation and polyadenylation of the cyclin B1 mRNA during
      zebrafish and Xenopus oocyte maturation. Polyadenylation and translational
      activation of cyclin B1 mRNA is well characterized during Xenopus oocyte
      maturation. Specifically, Xenopus cyclin B1 mRNA is polyadenylated and
      translationally activated during oocyte maturation by proteins that recognize the
      conserved AAUAAA hexanucleotide and U-rich Cytoplasmic Polyadenylation Elements
      (CPEs) within cyclin B1 mRNA's 3'UnTranslated Region (3'UTR). RESULTS: The
      zebrafish cyclin B1 mRNA was polyadenylated during zebrafish oocyte maturation.
      Furthermore, the zebrafish cyclin B1 mRNA's 3'UTR was sufficient to stimulate
      translation of a reporter mRNA during zebrafish oocyte maturation. This
      stimulation required both AAUAAA and U-rich CPE-like sequences. However, in
      contrast to AAUAAA, the positions and sequences of the functionally defined CPEs
      were poorly conserved between Xenopus and zebrafish cyclin B1 mRNA 3'UTRs. To
      determine whether these differences were relevant to translation efficiency, we
      analyzed the translational activity of reporter mRNAs containing either the
      zebrafish or Xenopus cyclin B1 mRNA 3'UTRs during both zebrafish and Xenopus
      oocyte maturation. The zebrafish cyclin B1 3'UTR was quantitatively less
      effective at stimulating polyadenylation and translation compared to the Xenopus
      cyclin B1 3'UTR during both zebrafish and Xenopus oocyte maturation. CONCLUSION:
      Although the factors that regulate translation of maternal mRNAs are highly
      conserved, the target sequences and overall sequence architecture within the
      3'UTR of the cyclin B1 mRNA have diverged to affect translational efficiency,
      perhaps to optimize levels of cyclin B1 protein required by these different
      species during their earliest embryonic cell divisions.

PMID- 19175934
TI  - Coding region structural heterogeneity and turnover of transcription start sites
      contribute to divergence in expression between duplicate genes.
AB  - BACKGROUND: Gene expression divergence is one manifestation of functional
      differences between duplicate genes. Although rapid accumulation of expression
      divergence between duplicate gene copies has been observed, the driving
      mechanisms behind this phenomenon have not been explored in detail. RESULTS: We
      examine which factors influence expression divergence between human duplicate
      genes, utilizing the latest genome-wide data sets. We conclude that the turnover
      of transcription start sites between duplicate genes occurs rapidly after gene
      duplication and that gene pairs with shared transcription start sites have
      significantly higher expression similarity than those without shared
      transcription start sites. Moreover, we find that most (55%) duplicate gene pairs
      do not retain the same coding sequence structure between the two duplicate copies
      and this also contributes to divergence in their expression. Furthermore, the
      proportion of aligned sequences in cis-regulatory regions between the two copies
      is positively correlated with expression similarity. Surprisingly, we find no
      effect of copy-specific transposable element insertions on the divergence of
      duplicate gene expression. CONCLUSIONS: Our results suggest that turnover of
      transcription start sites, structural heterogeneity of coding sequences, and
      divergence of cis-regulatory regions between copies play a pivotal role in
      determining the expression divergence of duplicate genes.

PMID- 19175935
TI  - Combined effects of functionally-oriented exercise regimens and nutritional
      supplementation on both the institutionalised and free-living frail elderly
      (double-blind, randomised clinical trial).
AB  - BACKGROUND: Consistently swelling proportion of the frail elderly within a modern
      society challenges the overstrained public health sector to provide both adequate
      medical care and comprehensive assistance in their multiple functional deficits
      of daily living. Easy-to-apply and task-specific ways of addressing this issue
      are being sought out, with a view to proposing systemic solutions for nationwide
      application. METHODS: The present randomised, double-blind, placebo-controlled, 7
      week clinical trial aimed to determine whether specifically structured, intensive
      exercise regimens, combined with nutritional supplementation, might improve and
      help sustain individual muscle strength and mobility, and possibly enhance
      individual functional capabilities in an on-going quest for active prevention of
      care-dependency. Ninety-one frail elderly (F 71 M 20; mean age 79 years) were
      recruited from both nursing home residents and community dwellers and randomly
      split into four groups: Group I - progressive resistance exercises (PRE) +
      functionally-oriented exercises (FOE) + nutritional supplementation (NS), Group
      II - PRE + FOE + placebo, Group III--standard exercises (SE) + FOE + NS, Group IV
      - SE + FOE + placebo. Each group pursued a 45 min. exercise session 5 times
      weekly. The subjects' strength with regard to four muscle groups, i.e. hip and
      knee extensors and flexons, was assessed at 80% (1 RM) weekly, whereas their
      balance and mobility at baseline and at the end of the study. RESULTS: The study
      was completed by 80 subjects. Despite its relatively short duration significant
      differences in muscle strength were noted both in Group I and Group II (p = 0.01;
      p = 0.04; respectively), although this did not translate directly into
      perceptible improvement in individual mobility. Notable improvements in
      individual mobility were reported in Group III and Group IV (p = 0.002), although
      without positive impact on individual muscle strength. CONCLUSION:
      Comprehensively structured, high-intensity regimen made up of diverse exercise
      types, i.e. functionally-oriented, progressive resistance and standard ones,
      preferably if combined with nutritional supplementation in adequate volume,
      demonstrates clear potential for appreciably improving overall functional status
      in the frail elderly in terms of individual walking capacity and muscle strength.
      TRIAL REGISTRATION: Central Register of Clinical Trials, Poland--CEBK180/2000.

PMID- 19175936
TI  - Molecular characterization of antifolates resistance-associated genes, (dhfr and
      dhps) in Plasmodium vivax isolates from the Middle East.
AB  - BACKGROUND: In Iran, co-infections of Plasmodium vivax and Plasmodium falciparum
      are common and P. vivax infections are often exposed to sulphadoxine
      pyrimethamine (SP). In the present study, the frequency distribution of mutations
      associated to SP resistance was investigated in pvdhfr and pvdhps genes from
      field isolates. METHODS: Clinical isolates of P. vivax were collected in two
      different malaria endemic regions in northern and south-eastern Iran, between
      2001 and 2006. All 189 collected isolates were analysed for SNP/haplotypes at
      positions 13, 33, 57, 58, 61, 117 and 173 of the pvdhfr and 383 and 553 of pvdhps
      genes using nested PCR-RFLP methods RESULTS: All 189 examined isolates were found
      to carry wild-type amino acids at positions 13, 33, 61 and 173, while 57L and 58R
      and 117N mutations in pure form was detected among 1.1%, 17.5% and 26% examined
      samples, respectively, with no polymorphisms in different loci of dhps genes.
      Based on size polymorphism of pvdhfr genes at repeat region, among northern
      isolates, the frequency distribution for type A and B were 2.2% and 97.8%
      respectively. However, in southern samples the prevalence of type A, B and C were
      7%, 89.5% and 7.7%, respectively. Mixed genotype infections (type B and C) were
      detected in only 4.2% (6/143) of southern, but in none of the northern isolates.
      The combination of pvdhfr and pvdhps haplotypes among all 189 samples
      demonstrated six distinct haplotypes. The two most prevalent haplotypes among all
      examined samples were I13P33F57S58T61S117I173/A383A553 (65.6%) and
      I13P33F57S58T61N117I173 (16.4%). Two other alleles with one point mutation
      I13P33F57R58T61S117I173/A383A553 and two mutations
      I13P33F57R58T61N117I173/A383A553 accounted for 7.4% and 9.5% of the total
      isolates. CONCLUSION: The present molecular data provide important information
      for making decisions on population based drug use in Iran. In addition, since
      October 2005, with more availability of SP as first-line treatment, P. vivax
      isolates are more exposed to SP and the selection or spread of resistant pvdhfr
      and pvdhps alleles might increase in the near future in this region.

PMID- 19175937
TI  - Activity of mevalonate pathway inhibitors against breast and ovarian cancers in
      the ATP-based tumour chemosensitivity assay.
AB  - Previous data suggest that lipophilic statins such as fluvastatin and N
      bisphosphonates such as zoledronic acid, both inhibitors of the mevalonate
      metabolic pathway, have anti-cancer effects in vitro and in patients. We have
      examined the effect of fluvastatin alone and in combination with zoledronic acid
      in the ATP-based tumour chemosensitivity assay (ATP-TCA) for effects on breast
      and ovarian cancer tumour-derived cells. Both zoledronic acid and fluvastatin
      showed activity in the ATP-TCA against breast and ovarian cancer, though
      fluvastatin alone was less active, particularly against breast cancer. The
      combination of zoledronic acid and fluvastatin was more active than either single
      agent in the ATP-TCA with some synergy against breast and ovarian cancer tumour
      derived cells. Sequential drug experiments showed that pre-treatment of ovarian
      tumour cells with fluvastatin resulted in decreased sensitivity to zoledronic
      acid. Addition of mevalonate pathway components with zoledronic acid with or
      without fluvastatin showed little effect, while mevalonate did reduced inhibition
      due to fluvastatin. These data suggest that the combination of zoledronic acid
      and fluvastatin may have activity against breast and ovarian cancer based on
      direct anti-cancer cell effects. A clinical trial to test this is in preparation.

PMID- 19175938
TI  - Systematic analysis of insertions and deletions specific to nematode proteins and
      their proposed functional and evolutionary relevance.
AB  - BACKGROUND: Amino acid insertions and deletions in proteins are considered
      relatively rare events, and their associations with the evolution and adaptation
      of organisms are not yet understood. In this study, we undertook a systematic
      analysis of over 214,000 polypeptides from 32 nematode species and identified
      insertions and deletions unique to nematode proteins in more than 1000 families
      and provided indirect evidence that these alterations are linked to the evolution
      and adaptation of nematodes. RESULTS: Amino acid alterations in sequences of
      nematodes were identified by comparison with homologous sequences from a wide
      range of eukaryotic (metzoan) organisms. This comparison revealed that the
      proteins inferred from transcriptomic datasets for nematodes contained more
      deletions than insertions, and that the deletions tended to be larger in length
      than insertions, indicating a decreased size of the transcriptome of nematodes
      compared with other organisms. The present findings showed that this reduction is
      more pronounced in parasitic nematodes compared with the free-living nematodes of
      the genus Caenorhabditis. Consistent with a requirement for conservation in
      proteins involved in the processing of genetic information, fewer insertions and
      deletions were detected in such proteins. On the other hand, more insertions and
      deletions were recorded for proteins inferred to be involved in the endocrine and
      immune systems, suggesting a link with adaptation. Similarly, proteins involved
      in multiple cellular pathways tended to display more deletions and insertions
      than those involved in a single pathway. The number of insertions and deletions
      shared by a range of plant parasitic nematodes were higher for proteins involved
      in lipid metabolism and electron transport compared with other nematodes,
      suggesting an association between metabolic adaptation and parasitism in plant
      hosts. We also identified three sizable deletions from proteins found to be
      specific to and shared by parasitic nematodes, which, given their uniqueness,
      might serve as target candidates for drug design. CONCLUSION: This study
      illustrates the significance of using comparative genomics approaches to identify
      molecular elements unique to parasitic nematodes, which have adapted to a
      particular host organism and mode of existence during evolution. While the focus
      of this study was on nematodes, the approach has applicability to a wide range of
      other groups of organisms.

PMID- 19175939
TI  - IL23R in the Swedish, Finnish, Hungarian and Italian populations: association
      with IBD and psoriasis, and linkage to celiac disease.
AB  - BACKGROUND: Association of the interleukin-23 receptor (IL23R) with inflammatory
      bowel disease (IBD) has been confirmed in several populations. IL23R also
      associates with psoriasis, suggesting that the gene may be an important candidate
      for many chronic inflammatory diseases. METHODS: We studied association of single
      nucleotide variants in IL23R with IBD in Swedish patients, in both Crohn's
      disease (CD) and ulcerative colitis (UC) subsets. The same genetic variants were
      also studied in Finnish patients with psoriasis or celiac disease, and in
      Hungarian and Italian patients with celiac disease. RESULTS: Association of IL23R
      with IBD was replicated in our Swedish patients, and linkage and association of
      the IL23R region with psoriasis was found in the Finnish population. The IL23R
      region was also linked to celiac disease in Finnish families, but no association
      of IL23R variants with celiac disease was found in the Finnish, Hungarian or
      Italian samples. CONCLUSION: Our study is the first to demonstrate association of
      IL23R with CD and UC in Swedish patients with IBD. It is also the first study to
      report linkage and association of the IL23R region with psoriasis in the Finnish
      population. Importantly, this is the first report of linkage of the IL23R region
      to celiac disease, a chronic inflammatory condition in which IL23R has not been
      previously implicated.

PMID- 19175940
TI  - Mucin 1 (MUC1) is a novel partner for MAL2 in breast carcinoma cells.
AB  - BACKGROUND: The MAL2 gene, encoding a four-transmembrane protein of the MAL
      family, is amplified and overexpressed in breast and other cancers, yet the
      significance of this is unknown. MAL-like proteins have trafficking functions,
      but their molecular roles are largely obscure, partly due to a lack of known
      binding partners. METHODS: Yeast two-hybrid screening of a breast carcinoma cDNA
      expression library was performed using a full-length MAL2 bait, and subsequent
      deletion mapping experiments were performed. MAL2 interactions were confirmed by
      co-immunoprecipitation analyses and confocal microscopy was employed to compare
      protein sub-cellular distributions. Sucrose density gradient centrifugation of
      membranes extracted in cold Triton X-100 was employed to compare protein
      distributions between Triton X-100-soluble and -insoluble fractions. RESULTS: The
      tumor-associated protein mucin 1 (MUC1) was identified as a potential MAL2
      partner, with MAL2/MUC1 interactions being confirmed in myc-tagged MAL2
      expressing MCF-10A cells using co-immunoprecipitation assays. Deletion mapping
      experiments demonstrated a requirement for the first MAL2 transmembrane domain
      for MUC1 binding, whereas the MAL2 N-terminal domain was required to bind D52
      like proteins. Confocal microscopy identified cytoplasmic co-localisation of MUC1
      and MAL2 in breast cell lines, and centrifugation of cell lysates to equilibrium
      in sucrose density gradients demonstrated that MAL2 and MUC1 proteins were co
      distributed between Triton X-100-soluble and -insoluble fractions. However co
      immunoprecipitation analyses detected MAL2/MUC1 interactions in Triton X-100
      soluble fractions only. Myc-MAL2 expression in MCF-10A cells was associated with
      both increased MUC1 detection within Triton X-100-soluble and -insoluble
      fractions, and increased MUC1 detection at the cell surface. CONCLUSION: These
      results identify MUC1 as a novel MAL2 partner, and suggest a role for MAL2 in
      regulating MUC1 expression and/or localisation.

PMID- 19175942
TI  - The biological effect of 125I seed continuous low dose rate irradiation in CL187
      cells.
AB  - BACKGROUND: To investigate the effectiveness and mechanism of 125I seed
      continuous low-dose-rate irradiation on colonic cell line CL187 in vitro.
      METHODS: The CL187 cell line was exposed to radiation of 60Cogamma ray at high
      dose rate of 2 Gy/min and 125I seed at low dose rate of 2.77 cGy/h. Radiation
      responses to different doses and dose rates were evaluated by colony-forming
      assay. Under 125I seed low dose rate irradiation, a total of 12 culture dishes
      were randomly divided into 4 groups: Control group, and 2, 5, and 10 Gy
      irradiation groups. At 48 h after irradiation, apoptosis was detected by Annexin
      and Propidium iodide (PI) staining. Cell cycle arrests were detected by PI
      staining. In order to investigate the influence of low dose rate irradiation on
      the MAPK signal transduction, the expression changes of epidermal growth factor
      receptor (EGFR) and Raf under continuous low dose rate irradiation (CLDR) and/or
      EGFR monoclonal antibodies were determined by indirect immunofluorescence.
      RESULTS: The relative biological effect (RBE) for 125I seeds compared with 60Co
      gamma ray was 1.41. Apoptosis rates of CL187 cancer cells were 13.74% +/- 1.63%,
      32.58% +/- 3.61%, and 46.27% +/- 3.82% after 2 Gy, 5 Gy, and 10 Gy irradiation,
      respectively; however, the control group apoptosis rate was 1.67% +/- 0.19%. G2/M
      cell cycle arrests of CL187 cancer cells were 42.59% +/- 3.21%, 59.84% +/- 4.96%,
      and 34.61% +/- 2.79% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively;
      however, the control group apoptosis rate was 26.44% +/- 2.53%. P < 0.05 vs.
      control groups by Student's t-test were found in every treated group both in
      apoptosis and in G2/M cell cycle arrest. After low dose rate irradiation, EGFR
      and Raf expression increased, but when EGFR was blocked by a monoclonal antibody,
      EGFR and Raf expression did not change. CONCLUSION: 125I seeds resulted in more
      effective inhibition than 60Co gamma ray high dose rate irradiation in CL187
      cells. Apoptosis following G2/M cell cycle arrest was the main mechanism of cell
      killing effects under low dose rate irradiation. CLDR could influence the
      proliferation of cells via MAPK signal transduction.

PMID- 19175941
TI  - Comparative transcriptomic analysis of Porphyromonas gingivalis biofilm and
      planktonic cells.
AB  - BACKGROUND: Porphyromonas gingivalis in subgingival dental plaque, as part of a
      mature biofilm, has been strongly implicated in the onset and progression of
      chronic periodontitis. In this study using DNA microarray we compared the global
      gene expression of a P. gingivalis biofilm with that of its planktonic
      counterpart grown in the same continuous culture. RESULTS: Approximately 18% (377
      genes, at 1.5 fold or more, P-value < 0.01) of the P. gingivalis genome was
      differentially expressed when the bacterium was grown as a biofilm. Genes that
      were down-regulated in biofilm cells, relative to planktonic cells, included
      those involved in cell envelope biogenesis, DNA replication, energy production
      and biosynthesis of cofactors, prosthetic groups and carriers. A number of genes
      encoding transport and binding proteins were up-regulated in P. gingivalis
      biofilm cells. Several genes predicted to encode proteins involved in signal
      transduction and transcriptional regulation were differentially regulated and may
      be important in the regulation of biofilm growth. CONCLUSION: This study
      analyzing global gene expression provides insight into the adaptive response of
      P. gingivalis to biofilm growth, in particular showing a down regulation of genes
      involved in growth and metabolic activity.

PMID- 19175943
TI  - Thrombin related peptide TP508 promoted fracture repair in a mouse high energy
      fracture model.
AB  - BACKGROUND: Thrombin related peptide (TP508) is a 23 amino-acid synthetic peptide
      that represents a portion of the receptor-binding domain of thrombin molecule.
      Previous studies have shown that TP508 can accelerate musculoskeletal tissue
      repair including fracture healing. OBJECTIVES: The aim of this study was to
      investigate the effect of TP508 on fracture healing in a murine fracture model
      representing high energy fracture situation. METHODS: Eighty CD 1 mice underwent
      controlled quadriceps muscle crush and open transverse mid diaphyseal femoral
      fracture that was then fixed with an external fixator. Animals were randomised
      into four groups to receive an intra-operative dose of either 100 mug TP508 into
      the fracture gap; 100 mug TP508 into the surrounding damaged muscle tissues; 10
      mug TP508 into the fracture gap, or control equal amount of saline into the
      fracture gap. Radiographic assessment was performed weekly for 5 weeks;
      histological analysis was at 3 and 5 weeks post fracture and biomechanical
      testing of the fractured bone was performed at 5 weeks post fracture. RESULTS:
      Mechanical testing data showed that the fracture stiffness was significantly
      higher in the group receiving 100 mug TP508 into the fracture gap than other
      groups. Histological and radiographic analysis revealed a trend of increase in
      bone formation in the 100 mug TP508 injected into the fracture gap group compared
      to the saline control group. It was noted that the scar tissues was significantly
      less in Group II comparing with the saline control group and there was increased
      blood vessel formation in the crushed muscles and fracture gap areas in the
      groups receiving TP508 comparing to the saline control group. CONCLUSION: The
      results from this study demonstrated the use of thrombin related peptide TP508 in
      the situation of a high energy fracture can promote fracture healing and reduce
      the potential complications such as muscle fibrosis and fracture delayed or non
      union.

PMID- 19175945
TI  - Novel foods: an explorative study into their grey area.
AB  - European Union Regulation 258/97 defines novel foods as food products and food
      ingredients that have not been consumed to a significant degree in the European
      Union before May 1997. However, there are new foods that for some reason are not
      considered as novel foods, though we think that safety of these products is not
      always a priori established. We defined a 'grey area' which consists of such
      foods, and the present paper intends to raise awareness of this 'grey area' of
      unidentified novel foods. The grey area of novel foods is divided into two
      categories: (1) food products or ingredients for which the current Regulation
      leaves too much space for different interpretations and (2) food products or
      ingredients that are not novel according to the current Regulation, because the
      current Regulation contains gaps. These categories are illustrated by means of
      products already on the market in The Netherlands. We found about two dozen
      examples of products that had not been identified as novel foods according the
      current Regulation, yet could be considered to be classified as novel foods and
      hence for which a safety evaluation (toxicological and/or nutritional) would be
      indicated.

PMID- 19175944
TI  - A compact phage display human scFv library for selection of antibodies to a wide
      variety of antigens.
AB  - BACKGROUND: Phage display technology is a powerful new tool for making antibodies
      outside the immune system, thus avoiding the use of experimental animals. In the
      early days, it was postulated that this technique would eventually replace
      hybridoma technology and animal immunisations. However, since this technology
      emerged more than 20 years ago, there have only been a handful reports on the
      construction and application of phage display antibody libraries world-wide.
      RESULTS: Here we report the simplest and highly efficient method for the
      construction of a highly useful human single chain variable fragment (scFv)
      library. The least number of oligonucleotide primers, electroporations and
      ligation reactions were used to generate a library of 1.5 x 108 individual
      clones, without generation of sub-libraries. All possible combinations of heavy
      and light chains, among all immunoglobulin isotypes, were included by using a
      mixture of primers and overlapping extension PCR. The key difference from other
      similar libraries was the highest diversity of variable gene repertoires, which
      was derived from 140 non-immunized human donors. A wide variety of antigens were
      successfully used to affinity select specific binders. These included pure
      recombinant proteins, a hapten and complex antigens such as viral coat proteins,
      crude snake venom and cancer cell surface antigens. In particular, we were able
      to use standard bio-panning method to isolate antibody that can bind to soluble
      Aflatoxin B1, when using BSA-conjugated toxin as a target, as demonstrated by
      inhibition ELISA. CONCLUSION: These results suggested that by using an optimized
      protocol and very high repertoire diversity, a compact and efficient phage
      antibody library can be generated. This advanced method could be adopted by any
      molecular biology laboratory to generate both naive or immunized libraries for
      particular targets as well as for high-throughput applications.

PMID- 19175946
TI  - Acute- phase response and iron status markers among pulmonary tuberculosis
      patients: a cross-sectional study in Mwanza, Tanzania.
AB  - Fe status is difficult to assess in the presence of infections. To assess the
      role of the acute- phase response (APR) and other predictors of serum ferritin
      and transferrin receptor, we conducted a cross-sectional study among pulmonary
      tuberculosis (PTB) patients in Mwanza, Tanzania. The acute- (serum ferritin)
      phase protein, serum alpha1-antichymotrypsin (ACT) and serum ferritin and serum
      soluble transferrin receptor (sTfR) were measured, and data on smoking, soil and
      alcohol intake, and infection status were collected. Linear regression analysis
      was used to assess the role of elevated serum ACT and other predictors of serum
      ferritin and serum sTfR. Of 655 patients, 81.2 % were sputum positive (PTB+) and
      47.2 % HIV+. Mean serum ACT was 0.72 g/l, with 91.1 % above 0.4 g/l. Among
      females and males, respectively, geometric mean serum ferritin was 140.9 and
      269.1 microg/l (P < 0.001), and mean serum sTfR 4.3 and 3.8 mg/l (P < 0.001).
      Serum sTfR was increased 0.5 mg/l and log serum ferritin increased linearly with
      serum ACT >0.4 g/l. PTB+ and HIV infection, alcohol drinking and smoking were the
      positive predictors of serum ferritin, and female sex, soil eating, Schistosoma
      mansoni and hookworm infection were the negative predictors. Similarly, smoking
      and HIV infection were the negative predictors of serum sTfR, and female sex,
      soil eating and PTB+ were the positive predictors. Serum ferritin and serum sTfR
      are affected by the APR, but may still provide information about Fe status. It
      may be possible to develop algorithms, based on the markers of the APR and Fe
      status, to assess the Fe status among the patients with tuberculosis or other
      infections eliciting an APR.

PMID- 19175947
TI  - Fatty acid pattern in serum is associated with bone mineralisation in healthy 8
      year-old children.
AB  - Animal studies have shown that fatty acids (FA) are important for normal bone
      development. Human data are scanty and mostly related to diseases. We
      hypothesised that serum FA pattern might be related to bone mineralisation in
      healthy children. Serum phospholipid FA pattern was studied in relation to bone
      parameters in eighty-five healthy Caucasian 8-year-olds. Dual-energy X-ray
      absorptiometry and blood sampling for analysis of serum phospholipid FA by
      capillary GLC were performed on the same day. SFA concentrations were associated
      with bone mineral density (BMD) of the hip, lumbar spine and total body. There
      was a general trend that linoleic acid (LA; 18 : 2n-6) was negatively associated
      with BMD, since that was found both for the LA concentration, the total n-6
      concentration and the ratio of n-6:n-3 FA. Arachidonic acid (AA; 20 : 4n-6) was
      positively correlated with bone mineral content (BMC) and BMD of total body, as
      was the corresponding z-score and the AA:LA ratio. Both saturated and
      polyunsaturated serum phospholipid FA were associated with BMC and BMD in healthy
      children. LA and AA were found to inversely influence bone mineralisation and the
      association with the n-6:n-3 ratio suggested that this balance might also be of
      importance. The general trend of a negative influence of high n-6 FA
      concentrations on bone mineralisation might be of concern in relation to the
      changes in the Western diet. Longitudinal studies are necessary to verify if
      different bone compartments and different grades of modelling are related to
      different FA patterns.

PMID- 19175948
TI  - Shorter adults, yet taller children: what's up?

PMID- 19175949
TI  - Consanguinity in Lebanon: prevalence, distribution and determinants.
AB  - The union of individuals with a common ancestor may lead to serious health
      consequences in their offspring. Consanguinity is high in Middle Eastern
      communities; it was around 26% in 1988. The objective of this study was to
      determine the prevalence of consanguinity in Beirut and other Lebanese regions,
      and its associated factors in different subgroups. The cross-sectional study was
      performed on a convenience sample of married women in Lebanon. The women were
      administered a standardized questionnaire in a face-to-face interview by
      independent enquirers. Among 1556 women, the overall prevalence of consanguineous
      marriages was 35.5%, and the consanguinity coefficient was 0.020; 968 marriages
      (62.2%) were not consanguineous, 492 (31.6%) were first cousin, 61 (3.9%) were
      second cousin and 36 (2.3%) had lower degrees of consanguinity. Beirut suburb
      dwelling, low education subgroups, women working in the home and non-Christian
      religion presented the highest rates of consanguinity (p<0.05). Consanguinity is
      associated with couples' nulliparity and child chronic morbidity. Factors that
      could affect consanguinity are having consanguineous parents, having a favourable
      opinion towards consanguinity, choosing a spouse for religious reasons,
      particularly in Islam, woman having a low education, woman working in the home
      and women thinking that consanguinity would not lead to serious diseases.
      Consanguinity is therefore still a prevailing problem in Lebanon. Specific health
      education, and genetic counselling in particular, are suggested to explain the
      consequences of consanguinity to the general population and to help couples make
      informed choices.

PMID- 19175950
TI  - Lineage based differences in grandparental investment: evidence from a large
      British cohort study.
AB  - Evolutionary theory suggests that maternal grandparents will invest more in their
      grandchildren than paternal grandparents, due to the difference between the
      certainty of maternity and the uncertainty of paternity. Most tests of this
      prediction have tended to use retrospective ratings by grandchildren rather than
      examining grandparental behaviour. Using a large-scale data set from the UK
      (n>7000), significant differences are shown between maternal and paternal
      grandparents in terms of frequencies of contact with their newborn grandchildren,
      while controlling for a wide range of other variables. Maternal grandparents also
      provided a significantly wider range of financial benefits than paternal
      grandparents. Maternal grandparents were also more likely to provide essentials
      and gifts and extras for the baby. Multiple correspondence analysis showed that
      contact frequencies systematically related to other measures of grandparental
      investment, indicating that contact frequencies are a useful proxy measure to
      examine overall investment. Findings are discussed with reference to the
      paternity uncertainty hypothesis.

PMID- 19175951
TI  - Dynamic posturography for staging of patients with Meniere's disease.
AB  - OBJECTIVE: In recent years, techniques such as computerised dynamic posturography
      have facilitated objective evaluation of patients with balance disorders. In this
      study, we used computerised dynamic posturography for clinical staging of
      Meniere's disease. MATERIAL AND METHODS: We applied a computerised dynamic
      posturography sensory organisation test to 53 patients with American Academy of
      Otolaryngology criteria of Meniere's disease. The following parameters were
      considered in data analysis: computerised dynamic posturography scores for
      testing the patient's centre of gravity with a mobile surface, immobile visual
      surroundings and eyes closed, scores for testing with a mobile surface, mobile
      visual surroundings and eyes open, and vestibular ratio. We used four hearing
      threshold stages (although we had no patients at stage four). RESULTS AND
      DISCUSSION: This study did not observe a statistically significant correlation
      between audiometric hearing thresholds and computerised dynamic posturography
      scores. Computerised dynamic posturography scores showed statistically
      significant variation with time elapsed since the last vertigo attack. Although
      our results showed an increasing trend in computerised dynamic posturography
      scores as Meniere's disease activity level decreased from recent post-attack
      (i.e. less than one week since last attack) through late post-attack (i.e. one
      week to 60 days since last attack) to inactive (i.e. more than 60 days since last
      attack), these differences were not statistically significant.

PMID- 19175952
TI  - Wegener's granulomatosis presenting as acute systemic vasculitis following 20
      years of limited tracheobronchial disease.
AB  - OBJECTIVE: We report a patient with a 20-year history of apparently idiopathic
      airways stenoses, who presented with an antineutrophil cytoplasmic antibody
      (ANCA) associated, acute, systemic vasculitis with necrotising
      glomerulonephritis, subsequently diagnosed as Wegener's granulomatosis. METHODS:
      We present a case report and a review of the world literature on airway stenosis
      in Wegener's granulomatosis. RESULTS: To our knowledge, this is the first report
      of Wegener's granulomatosis manifesting as local airway disease for such a
      prolonged period, before transforming into a systemic vasculitis. CONCLUSIONS:
      This case highlights the need for physicians to be alert to the possibility of
      Wegener's granulomatosis as a cause of apparently idiopathic airway stenosis, and
      to be aware that systemic disease may occur in very long-standing, limited
      Wegener's granulomatosis.

PMID- 19175953
TI  - A dominant hereditary ossicular anomaly: bilateral incus anomaly and stapes
      fixation.
AB  - OBJECTIVE: We report three generations of one family suffering from bilateral
      conductive hearing loss due to a congenital anomaly of the incus and stapes
      fixation. CASE REPORT: All three female patients presented with similar symptoms
      and findings of hearing impairment since birth. Their computed tomography
      findings were the same. An abnormally shaped incus, fixed stapes and hanging
      tympanic portion of the facial nerve were seen at surgery. Stapedotomy could not
      be performed because the hanging facial nerve blocked the operating field.
      CONCLUSION: Although several cases of familial ossicular anomaly have been
      reported, this is the first report of an incus anomaly and stapes fixation
      combined with a facial nerve anomaly.

PMID- 19175954
TI  - Trigeminal nerve haemangioma eroding the petrous carotid canal.
AB  - OBJECTIVE: To report the first case of mandibular branch haemangioma of the
      trigeminal nerve causing erosion of the petrous carotid canal. The radiological
      and histological findings in this case are reviewed. CASE REPORT: A 60-year-old
      woman presented with severe, right-sided facial pain and paraesthesia. There were
      no associated symptoms of facial weakness or diplopia. A magnetic resonance
      imaging scan with gadolinium enhancement was performed. This showed a lesion
      slightly compressing the right Meckel's cave and eroding the right petrous
      carotid canal, occupying the foramen ovale and extending to the pterygoid muscle.
      The lesion was removed via a subtemporal approach. CONCLUSION: Haemangiomas are
      usually found on the skin and in other soft tissues. However, this rare tumour
      should also be considered in the differential diagnosis of lesions occupying
      Meckel's cave and the foramen ovale.

PMID- 19175955
TI  - The developmental potential of mouse somatic cell nuclear-transferred oocytes
      treated with trichostatin A and 5-aza-2'-deoxycytidine.
AB  - To facilitate nuclear reprogramming, somatic cells or somatic cell nuclear
      transferred (SCNT) oocytes have been treated with the histone deacetylase
      inhibitor trichostatin A (TSA), or the DNA methyltransferase inhibitor, 5-aza-2'
      deoxycytidine (5-aza-dC), to relax epigenetic marks of differentiated somatic
      cells. TSA-treated SCNT oocytes have increased developmental potential, but the
      optimal treatment period is unknown. Reduced methylation levels in somatic cells
      have no positive effect on SCNT oocytes, but the treatment of SCNT embryos with 5
      aza-dC has not been investigated. We examined the effect of TSA treatment
      duration on the developmental potential of mouse SCNT oocytes and the effect of 5
      aza-dC treatment on their in vitro and in vivo developmental potential. To
      determine the effects of TSA treatment duration, nuclear-transferred (NT) oocytes
      were cultured for 0 to 26 h with 100 nM TSA. SCNT oocytes treated with TSA for 8
      to 12 h had the higher rate of development to blastocysts and full-term fetuses
      were obtained after treatment for 8 to 12 h. When oocytes were treated for 14 h
      and 26 h, blastocyst rates were significantly decreased and fetuses were not
      obtained. To examine the effect of 5-aza-dC, 2-cell stage SCNT embryos were
      cultured with 10 or 100 nM 5-aza-dC for 48 h to the morula stage and transferred.
      The potential of embryos treated with 5-aza-dC to develop into blastocysts was
      decreased and no fetuses were obtained after transfer. The findings demonstrated
      that long-term TSA treatment of SCNT mouse oocytes and treatment with 5-aza-dC
      inhibit the potential to develop into blastocysts and to fetuses after transfer.

PMID- 19175956
TI  - Vulvar endometriosis.

PMID- 19175958
TI  - Traditions.

PMID- 19175960
TI  - Uterine wall partial thickness necrosis following combined B-Lynch and cho square
      sutures for the treatment of primary postpartum hemorrhage.

PMID- 19175961
TI  - Self-reported protective behaviour against West Nile Virus among pregnant women
      in Toronto.
AB  - OBJECTIVE: West Nile virus (WNV) is an emerging infection that can lead to
      substantial morbidity and mortality. Although data are limited with respect to
      the risk to the fetus and neonate, this risk is not inconsequential. Methods to
      reduce the risk of mosquito bites and WNV transmission are simple, economical,
      and effective in the non-pregnant population. The objective of this descriptive
      cross-sectional study was to assess adherence to protective behaviours against
      WNV in pregnant women and to determine predictors for such adherence. METHODS: A
      questionnaire was administered to all consenting pregnant women at two Toronto
      university hospitals. RESULTS: The majority of women reported practising
      behaviours that reduce the risk of mosquito bites and potentially of WNV
      infection. In this survey, between 40% and 80% of pregnant women avoided the
      outdoors, avoided areas with mosquitoes, and reported practising two or more
      personal protection behaviours. However, only 33% of pregnant women reported
      wearing mosquito repellent, with the majority expressing concern about the safety
      of repellent use during pregnancy. The majority of pregnant women cited the media
      or the Internet as a source of their knowledge about WNV; only 12% reported their
      physician as a source of such knowledge. CONCLUSION: The majority of pregnant
      women are aware of WNV and practise protective behaviours that reduce the risk of
      transmission. However, they have unjustified fetal safety concerns about the use
      of mosquito repellent and are thus less likely to use it.

PMID- 19175962
TI  - Compliance with a perinatal prophylaxis policy for prevention of venous
      thromboembolism after caesarean section.
AB  - OBJECTIVE: To assess physician compliance, before and after a quality improvement
      intervention, with a regional policy on postpartum thromboprophylaxis following
      Caesarean section (CS), and to compare clinical outcomes (reduction of venous
      thromboembolism or increase in postpartum bleeding) between groups. METHODS: We
      performed a retrospective chart review of deliveries by CS, 404 prior to and 451
      subsequent to a quality improvement intervention. All subjects were classified as
      being at either moderate or high risk for venous thromboembolism based on a risk
      factor assessment, and warranted postpartum thromboprophylaxis according to the
      regional policy. Data regarding thromboembolism risk factors, postpartum
      thromboprophylaxis received, and clinical outcomes were recorded. RESULTS:
      Initial compliance with the regional policy was poor, but improved following the
      intervention. The use of intermittent pneumatic compression devices increased
      from 32% to 84% (P < 0.001), use of anticoagulation increased from 6.2% to 46% (P
      < 0.001), and full compliance with the policy increased from 1.7% to 30% (P <
      0.001). Clinical outcomes were not significantly different between the groups.
      CONCLUSION: A quality improvement intervention markedly increased physician
      compliance with a regional policy on postpartum thromboprophylaxis among women at
      moderate to high risk of venous thromboembolism after CS. Adverse clinical
      outcomes were infrequent in this small study population.

PMID- 19175963
TI  - Effectiveness of acupuncture for the initiation of labour at term: a pilot
      randomized controlled trial.
AB  - OBJECTIVE: This study was designed to determine the effectiveness of acupuncture
      for the initiation of labour in women at term. METHODS: A prospective pilot
      randomized control trial was undertaken, in which 16 pregnant women at term were
      randomly assigned to receive acupuncture either at sites reported to cause onset
      of labour or at nearby sham sites. The primary outcome assessed was the interval
      from initial acupuncture treatment to delivery. RESULTS: There was a difference
      in intervention to delivery interval of 62 hours in favour of the treatment
      group. Furthermore, women in this group had shorter labours by a mean of 2 hours
      and 20 minutes. CONCLUSION: The interesting results of this pilot trial warrant
      further investigation into the use of acupuncture for the initiation of labour in
      women at term.

PMID- 19175964
TI  - Cervix length and relaxin as predictors of preterm birth.
AB  - BACKGROUND: Measurement of mid-gestation cervix length has become a common
      screening tool for preterm birth. Our study was designed to assess the value of
      cervix length and serum relaxin in the prediction of spontaneous preterm birth at
      < 35 and < 37 weeks' gestation in a general obstetric population. METHODS: A
      prospective cohort of women with a singleton pregnancy had blood collected at 24
      and 28 weeks' gestation for determination of serum relaxin immediately before
      transvaginal ultrasound measurement of cervical length. Patients and referring
      physicians were blinded to cervix length and relaxin levels to preclude changes
      in management. The primary outcomes were spontaneous delivery at < 35 and < 37
      weeks' gestation. RESULTS: A total of 1004 women entered the study. Delivery data
      were not available for 20 women who delivered elsewhere. Twenty women were
      excluded because preterm delivery was undertaken because of pregnancy
      abnormalities. Of the 964 women with known gestational age at delivery, 46 (4.8%)
      delivered at < 37 weeks and 16 (1.7%) at < 35 weeks' gestation. Mean cervix
      length at 28 weeks (36.7 +/- 7.3 mm) was significantly shorter than at 24 weeks
      (37.8 +/- 7.1 mm) (P < 0.001). Cervix length at 24 and 28 weeks' gestation was
      equally predictive of preterm birth. A cervix length of < or = 30 mm at 28 weeks
      had a sensitivity of 57.1%, a specificity of 81.8%, and a positive predictive
      value of 4.5% for birth at < 35 weeks. Serum relaxin levels were not correlated
      with cervix length at either 24 or 28 weeks. Serum relaxin at 24 and 28 weeks'
      gestation was not associated with preterm birth before or after controlling for
      patient characteristics and cervix length. CONCLUSION: Serum relaxin levels at 24
      and 28 weeks' gestation are not associated with preterm birth. Although cervix
      length is associated with preterm birth, its positive predictive value is low.
      Given the lack of proven therapies for those at risk, cervix length does not
      appear to be a useful screening tool for preterm delivery in the general
      obstetric population.

PMID- 19175965
TI  - Maternal obesity and the risk of placental vascular disease.
AB  - INTRODUCTION: While elevated maternal weight in early pregnancy is associated
      with a higher rate of preeclampsia, the risk of placental abruption and placental
      infarction is unknown. METHODS: We evaluated the risk of placental abruption,
      placental infarction, and preeclampsia in association with maternal weight
      quintile at approximately 17 weeks' gestation in 386 323 women with a singleton
      pregnancy who underwent maternal serum screening in Ontario. RESULTS: After
      adjusting for age, ethnicity, parity, diabetes mellitus, and tobacco use, the
      odds ratio (OR) for preeclampsia was 4.1 (95% confidence interval [CI] 3.8-4.4)
      comparing the highest and lowest weight quintiles. Conversely, there was a lower
      risk of placental abruption or placental infarction, despite further adjustment
      for preeclampsia, gestational hypertension and drug dependence (OR 0.81, 95% CI
      0.75-0.87). CONCLUSION: Higher maternal weight in early pregnancy is associated
      with a higher risk of preeclampsia and a lower risk of placental abruption or
      placental infarction, a seeming paradox that requires further elucidation.

PMID- 19175966
TI  - Management of ectopic pregnancy through a posterior colpotomy: two cases.
AB  - BACKGROUND: Prior to the availability of modern laparoscopic surgical techniques
      and equipment, ectopic pregnancy was managed predominately by laparotomy. An
      alternative surgical approach, by posterior colpotomy, was advocated as a
      diagnostic and a therapeutic approach that often avoided laparotomy. CASES: We
      report two recent cases in which ectopic pregnancies were managed by posterior
      colpotomy to avoid any scars on the abdomen. One case involved a salpingectomy
      and the other a salpingostomy. CONCLUSION: Posterior colpotomy is a safe, cost
      effective, and time efficient method of managing ectopic pregnancy.

PMID- 19175967
TI  - Society of obstetricians and gynaecologists of Canada junior member committee
      survey: future career plans of Canadian obstetrics and gynaecology residents.
AB  - OBJECTIVE: Although the SOGC Strategic Directions 2006-2011 includes a commitment
      to the development of a human resource strategy for obstetrical and
      gynaecological care, little is known about the career plans of Canadian
      obstetrics and gynaecology residents. If we are to determine the needs of our
      profession, we must be aware of the expected practice patterns of future women's
      health care providers. The primary objective of this study was to evaluate the
      future career plans of Canadian obstetrics and gynaecology residents. METHODS:
      The SOGC Junior Member Committee administered two career surveys to Canadian
      obstetrics and gynaecology residents. The first was directly distributed to all
      Canadian residents and collected by local representatives of the SOGC Junior
      Member Committee in November 2002. The second was electronically administered
      from November 2005 to January 2006. The data collected from the surveys were
      collated and analyzed using statistical analysis software. RESULTS: The first
      survey, in 2002, was completed by 236 obstetrics and gynaecology residents (68%
      response rate) and the second, in 2006, by 246 (65% response rate). In both
      surveys, respondents were evenly distributed over all five years of residency
      training and all residency training programs. In 2002, 63 residents (30%) were
      considering additional postgraduate fellowship training following completion of
      residency compared with 130 residents (53%) in 2006 (P < 0.001). In both surveys,
      senior residents (postgraduate years IV and V) were significantly less likely to
      consider further postgraduate training than residents in their first three years
      (2002: 17% vs. 38%; 2006: 42% vs. 58%). Of total respondents to the 2002 and 2006
      surveys, 87% planned to practice obstetrics upon graduation. The 2006 survey also
      found that the majority of residents desired to work in call groups of 6 to 10
      physicians, work three to five on-call shifts per month, and work a 40- to 60
      hour week; 44% of residents planned work as locums after graduation. CONCLUSION:
      Recognition of the planned practice patterns of our current residents may assist
      in the development of an appropriate human resource strategy for future
      obstetrical and gynaecological care in Canada.

PMID- 19175968
TI  - Does treatment with bisphosphonates endanger the human pregnancy?
AB  - Bisphosphonates are clinically used in the treatment of various bone diseases
      including corticosteroid-induced osteoporosis, hypercalcemia associated with
      malignancy, and osteogenesis imperfecta. They are therefore often used in women
      of childbearing age, but little is known about their possible effects on the
      human embryo and fetus. Animal studies have revealed unfavourable effects of
      bisphosphonate treatment on the fetus, mainly in the skeleton. Since
      bisphosphonates are retained for a long time in the human skeleton, concerns have
      been raised that even pre-pregnancy administration of bisphosphonates may result
      in embryofetal exposure and alter fetal bone modelling. To obtain current
      information on the risks and safety of bisphosphonate use in pregnancy, we
      performed a systematic search of the Medline and Embase databases, from 1950 and
      1974, respectively, to September 2008. Fifty-one cases of exposure to
      bisphosphonates before or during pregnancy were identified; none of them
      described any skeletal abnormalities or other congenital malformations in the
      infants. The bisphosphonates used were alendronate (32 cases), pamidronate (11),
      etidronate (5), risedronate (2), and zoledronic acid (1). Although in theory
      bisphosphonates may affect bone modelling and development in the fetus, the 51
      cases reported to date did not detect such pathology.

PMID- 19175969
TI  - Immunization in pregnancy.
AB  - OBJECTIVE: To review the evidence and provide recommendations on immunization in
      pregnancy. OUTCOMES: Outcomes evaluated include effectiveness of immunization,
      and risks and benefits for mother and fetus. EVIDENCE: The Medline and Cochrane
      databases were searched for articles published up to June 2007 on the topic of
      immunization in pregnancy. VALUES: The evidence obtained was reviewed and
      evaluated by the Infectious Diseases Committee of the Society of Obstetricians
      and Gynaecologists of Canada (SOGC) under the leadership of the principal
      authors, and recommendations were made according to guidelines developed by the
      Canadian Task Force on Preventive Health Care. BENEFITS, HARMS, AND COSTS:
      Implementation of the recommendations in this guideline should result in more
      appropriate immunization of pregnant and breastfeeding women, decreased risk of
      contraindicated immunization, and better disease prevention. Recommendations 1.
      All women of childbearing age should be evaluated for the possibility of
      pregnancy before immunization. (III-A) 2. Health care providers should obtain an
      immunization history from all women accessing prenatal care. (III-A) 3. In
      general, live and/or live-attenuated virus vaccines are contraindicated during
      pregnancy, as there is a, largely theoretical, risk to the fetus. (II-3) 4. Women
      who have inadvertently received immunization with live or live-attenuated
      vaccines during pregnancy should not be counselled to terminate the pregnancy
      because of a teratogenic risk. (II-2) 5. Non-pregnant women immunized with a live
      or live-attenuated vaccine should be counselled to delay pregnancy for at least
      four weeks. (III) 6. Inactivated viral vaccines, bacterial vaccines, and toxoids
      are considered safe in pregnancy. (II-1) 7. Women who are breastfeeding can still
      be immunized (passive-active immunization, live or killed vaccines). (II-1) 8.
      Pregnant women should be offered the influenza vaccine when pregnant during the
      influenza season. (II-1).

PMID- 19175970
TI  - [Immunization in pregnancy].

PMID- 19175973
TI  - Many hands make light work: Thank You.

PMID- 19175974
TI  - Brains under stress.

PMID- 19175975
TI  - What stress does to your brain: a review of neuroimaging studies.
AB  - OBJECTIVE: Recent neuroimaging studies aimed at investigating effects of
      psychological stress on the neural activity have used a range of experimental
      paradigms to elicit an acute stress response. The goal of this review is to,
      first, summarize results from these studies from a perspective of task design
      and, second, assess the appropriateness of the different stress tasks used.
      METHOD: We completed a PubMed search on recent articles that have examined the
      effects of psychological stress on neural processes in a neuroimaging
      environment. Selected articles were arranged according to the stress task used in
      the following categories: script-driven stress stimuli, Stroop colour-word
      interference task, speech in front of an audience, serial subtraction, and
      Montreal Imaging Stress Task (MIST). RESULTS: Only studies using serial
      subtraction or the MIST were able to induce a significant cortisol stress
      response in their participants. Most consistent findings include decreased
      activity in orbitofrontal regions in response to stress. Additional findings of
      note are increases in activity in the frontal lobes, particularly the anterior
      cingulate cortex, as well as deactivation of the limbic system, particularly the
      hippocampus. CONCLUSION: Research to date is beginning to outline the involvement
      of prefrontal and limbic regions in perception and modulation of psychological
      stress. However, additional research is needed in designing a neuroimaging stress
      task that will yield a significant cortisol stress response consistently, across
      populations and laboratories.

PMID- 19175976
TI  - Imaging stress effects on memory: a review of neuroimaging studies.
AB  - OBJECTIVE: To review and give an overview of neuroimaging studies that look at
      the role of stress (hormones) on memory. METHOD: An overview will be given of
      imaging studies that looked at the role of stress (hormones) on memory. Stress is
      here defined as the acute provocation of the sympathetic adrenal medullar system
      and the hypothalamic-pituitary-adrenal axis in experimental designs. Stress
      hormone levels can be raised endogenously in response to stimulus material (for
      example, pictures and films) or social evaluative threat situations (stress
      tasks). Other studies use the exogenous application of drugs to enhance or
      decrease stress hormone levels. Finally, we review studies on chronic stress and
      memory. RESULTS: Stress or emotional arousal, leading to increased noradrenaline
      or cortisol levels, led to better memory performance when it is applied during
      perception or encoding. Brain regions involved in this process were medial
      temporal lobe regions such as amygdala and hippocampus, and several parts of the
      prefrontal cortex (PFC). High stress levels accompanied by high cortisol levels
      during retrieval led to impaired memory performance. Sex effects on memory as
      well as lateralization effects on brain activation were found. CONCLUSION: High
      stress levels during encoding and consolidation of emotional material involve
      increased amygdala and hippocampus activation. The role of the anterior cingulate
      cortex and other parts of the PFC during perception and encoding of arousing
      material appears to be a modulating one. However, additional research is needed
      to shed more light on the nature of the brain changes during stress, especially
      during retrieval.

PMID- 19175977
TI  - Early predictors of nonadherence to antipsychotic therapy in first-episode
      psychosis.
AB  - OBJECTIVE: To examine the hypothesis that poorer social and family support,
      identifiable at the onset of treatment, is associated with nonadherence in the
      first 6 months of treatment of patients with first-episode psychosis (FEP),
      independent of other patient-related factors. METHOD: Consecutive patients (n =
      100) admitted to a specialized early intervention service for FEP who met the
      Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria
      for either a schizophrenia spectrum disorder or an affective psychosis were
      evaluated monthly for 6 months regarding their adherence to medications. Using
      sociodemographic and illness-related factors, including social and family
      support, as independent variables and adherence as the dependent variable,
      univariate analyses were followed by logistic regression. RESULTS: Fifty-six
      patients (54.9%) were adherent (76% to 100% of doses taken) and 46 (45.1%)
      nonadherent (less than 76% of doses taken). Nonadherent patients were less likely
      to have received a good level of social support (chi (2) = 5.89, df = 1, P =
      0.02), as rated by their respective case manager, and more likely to be single
      (Fisher exact test, P = 0.019) and to have refused medication at the first offer
      of treatment (chi (2) = 19.70, df = 1, P = 0.001). Using logistic regression,
      both the level of social support (OR = 3.552, P = 0.03) and early medication
      acceptance (OR = 11.092, P < 0.001) were significant as predictors of adherence.
      CONCLUSION: These results suggest the significance of social and family support
      in achieving adherence to medications very early in the course of treatment of
      FEP, in addition to the influence of early acceptance or rejection of medication.

PMID- 19175978
TI  - Cigarette smoking, nicotine dependence, and motivation for smoking cessation in
      psychiatric inpatients.
AB  - OBJECTIVE: Cigarette smoking is the leading preventable cause of death and
      disease in Canada, and is disproportionately more frequent among psychiatric
      patients. Smoking cessation interventions can be successfully implemented with
      psychiatric patients, yet no Canadian studies have evaluated smoking prevalence,
      nicotine dependence, and motivation for smoking cessation in psychiatric
      inpatients. Our study did so to help plan appropriate interventions for these
      patients. METHOD: All inpatients aged 18 years or older admitted to acute-care
      psychiatry units at the Foothills Medical Centre in Calgary, Alberta, during a 6
      month period completed a survey involving questions from the Canadian Tobacco Use
      Monitoring Survey, the Fagerstrom Test for Nicotine Dependence (FTND), the
      Readiness to Quit Ladder, and the Decisional Balance for Cigarette Smoking.
      Responses were analyzed for correlation with discharge diagnoses, age, and sex.
      RESULTS: Among the total inpatients (n = 342), 211 (62%) completed the survey.
      Among those, 55% were current cigarette smokers and 17.5% were former smokers.
      Nicotine dependence (FTND > or = 6) was reported in 45.2% of smokers. Smoking
      prevalence and nicotine dependence severity was greatest in the substance use
      disorders (SUD) and psychotic disorders groups. Current smokers endorsed more
      negative than positive attributes of smoking. Regarding smoking cessation, 51% of
      patients were precontemplative, 12.7% contemplative, and 36.2% preparatory or
      action-oriented, despite few receiving advice to quit. CONCLUSIONS: Cigarette
      smoking and nicotine dependence are highly prevalent in psychiatric inpatients.
      However, self-reported motivation for smoking cessation is noteworthy,
      emphasizing that cessation advice and appropriate follow-up care should be
      provided to psychiatric inpatients who smoke.

PMID- 19175979
TI  - A comparison of ziprasidone and risperidone in the long-term treatment of
      schizophrenia: a 44-week, double-blind, continuation study.
AB  - OBJECTIVE: This randomized, double-blind, multicentre extension study compared
      the efficacy, tolerability, and safety of ziprasidone and risperidone for
      schizophrenia or schizoaffective disorder. METHODS: Patients who had responded to
      treatment for an acute exacerbation of illness in an 8-week study received
      ziprasidone, 80 to 160 mg/day (n = 62), or risperidone, 6 to 10 mg/day (n = 77),
      for up to 44 additional weeks. Primary efficacy variables included changes in
      Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global
      Impression Severity (CGI-S) score. Tolerability and safety assessments included
      movement disorders, adverse events, study discontinuation rates, and weight and
      metabolic parameters. RESULTS: Both the ziprasidone and risperidone groups showed
      statistical improvement from baseline in PANSS and CGI-S scores at study end
      point with no significant differences between treatment groups. More risperidone
      treated patients completed the study (41.6%) than ziprasidone-treated patients
      (33.9%), but the difference was not statistically significant. Ziprasidone
      treated patients who completed the study showed greater improvement in depressive
      symptoms assessed by Montgomery and Asberg Depression Rating Scale than
      risperidone-treated patients (P < 0.05). Ziprasidone was associated with a more
      favourable effect on extrapyramidal symptom (EPS) measures and prolactin as well
      as less weight gain than risperidone. Median dosages were ziprasidone 120 mg/day
      and risperidone 8 mg/day. CONCLUSIONS: Ziprasidone and risperidone demonstrated
      similar efficacy during long-term treatment of patients with schizophrenia or
      schizoaffective disorder. While more subjects on risperidone completed the
      extension study, ziprasidone was associated with fewer adverse effects on weight,
      EPS measures, and prolactin than risperidone.

PMID- 19175980
TI  - Immediate and sustained effects of parenting on physical aggression in Canadian
      children aged 6 years and younger.
AB  - OBJECTIVE: To determine whether the effects of factors associated with the
      development of childhood (aged 6 years or younger) physical aggression were
      immediate (cross-sectional), sustained (longitudinal), or both. METHODS: A
      longitudinal subsample (n = 975) of children born between December 1994 and April
      1995 was drawn from the Canadian National Longitudinal Survey of Children and
      Youth and followed from birth to 6 years of age. Using random- and fixed-effects
      logistic panel regression models, child (sex and preterm birth), maternal
      (education, employment, and positive or hostile/ineffective parenting), and
      family (lone-parent, older and younger siblings, and income) indicators were
      regressed on childhood physical aggression. RESULTS: Hostile/ineffective
      parenting contributed significantly to explaining the variance in aggression. At
      each measurement time point (birth, 2, 4, and 6 years of age), a change in
      hostile/ineffective parenting had an effect on aggression, and this effect
      carried forward across time up to 6 years. Being a boy, having a mother with less
      education, and living in a lone-parent family with siblings also contributed
      significantly to aggression. Preterm birth, maternal employment, depressive
      symptoms, positive interaction, and income failed to contribute significantly to
      aggression. CONCLUSIONS: These results support the hypothesis that
      hostile/ineffective parenting has an immediate effect on aggression. Contrary to
      predictions that it would have an immediate effect only at the time it was
      occurring, hostile/ineffective parenting had a sustained effect on aggression
      that carried forward in time up to 6 years of age. The results suggest that
      hostile/ineffective parenting has an effect on aggression prior to any evidence
      of aggressive behaviour in the child.

PMID- 19175981
TI  - [Molecular mechanisms of Glanzmann thrombasthenia caused by alpha II b L721R and
      Q860X compound heterozygous mutation].
AB  - OBJECTIVE: To explore the molecular mechanisms of Glanzmann thrombasthenia caused
      by alpha II b L721R and Q860X compound heterozygous mutation. METHODS: All exons
      and exon-intron boundaries of alpha II b and beta3 gene were amplified by PCR and
      analyzed by direct DNA sequencing. Gene polymorphisms were excluded by direct DNA
      sequencing. Alpha II b L721R and Q860X mutants expressing vectors were
      constructed by in vitro site-directed mutagenesis. The expression of alpha II b
      L721R and Q860X mutants on transfected cell membrane were analyzed by flow
      cytometry and the whole expression level was confirmed by Western blot. The
      subcellular localizations of alpha II b L721R and Q860X mutants were determined
      by immunofluorescent confocal scanning microscopy. RESULTS: The alpha II b
      compound heterozygous mutations, T2255G (L721R) and C2671T (Q860X), were
      identified in the proband, the former being inherited from the maternal side and
      the latter the paternal side. The 293T cells cotransfected with mutated alpha II
      b L721R and wild-type beta3 expression plasmids expressed 2.1% of normal amount
      of alpha II b on the cell surface as shown by FACS, in contrast to 31.9% of
      normal amount of alpha II b on the cells cotransfected with cDNAs of mutated
      alpha II b Q860X and wildtype beta3 expression plasmids. Western blot of the cell
      lysates showed no detectable mature alpha II b in cells lysates with L721R
      mutant. While, truncated alpha II b protein was detected in cell lystes with
      Q860X mutant. Immunofluorescence studies demonstrated that both L721R and Q860X
      mutant pro-alpha II bbeta33 complex colocalized in endoplasmic reticulum, but a
      little in Golgi. CONCLUSIONS: The L721R and Q860X mutations of alpha II b prevent
      transport of the pro-alpha II bbeta3 complex from the endoplasmic reticulum to
      the Golgi, hindering its maturation and surface expression. The impaired alpha II
      bbeta3 transport is responsible for the thrombasthenia.

PMID- 19175982
TI  - [In vitro expression of hemophilia B gene mediated by lentivirus].
AB  - OBJECTIVE: To construct a three plasmids lentiviral vector containing canine
      coagulation factor IX (cFIX) gene with ubiquinone promoter (PUB) and observe the
      expression of cFIX gene. METHODS: Lentivirus was generated by transient three
      plasmid transfection, namely, the VSV-G envelope expression cassette, the delta
      NRF packaging plasmid and the PTK 164 plasmid. Viral particles were used to
      infect the target cell, third passage mesenchymal stem cells (MSCs) and 293T cell
      respectively at MOI 3: 1. The cFIX activity was detected in cultured cells with
      one-stage clotting assay. RESULTS: The MSCs were obtained in vitro. The
      lentivirus infected MSCs and 293T cells all expressed the active factor IX with
      the activity of (26.30 +/- 2.10)% and (19.70 +/- 1.53)%, respectively, which are
      significantly higher than that of control (1.00 +/- 0.05)%. CONCLUSIONS: The
      lentiviral vector of three plasmids with ubiquinone promoter (PUB) was
      constructed and can transfect the MSCs and 293T cells.

PMID- 19175983
TI  - [Clinical analysis of 438 patients with essential thrombocythemia].
AB  - OBJECTIVE: To analyse the clinical feature and natural course of essential
      thrombocythemia (ET). METHODS: A retrospective analysis was conducted in ET
      patients treated in our hospital during May 1980 to December 2006. RESULTS: Four
      hundred and thirty eight patients (201 males and 237 females with a median age of
      48 years) were diagnosed. Hemorrhage occurred in 101 cases (23.1%), thrombosis in
      86 cases (19.6%), and both hemorrhage and thrombosis in 13 cases (3.0%).
      Splenomegaly occurred in 150 cases and hepatomegaly occurred in 60 cases. One
      hundred and forty-nine cases (34%) had no symptoms at diagnosis and 145 cases
      (33.1%) confirmed by routine blood tests due to other diseases. The median
      platelet count at diagnosis was 1000 x 10(9)/L [(533 -3740) x 10(9)/L]. Bone
      marrow biopsy was performed in 255 cases which showed mainly increase of enlarged
      mature megakaryocytes with hyper-lobulated nuclei and local proliferation of
      reticular fiber was revealed in 51 cases. JAK2V617F mutation was detected in
      90(78.9%) of 114 patients studied. Karyotype analysis was performed in 180 cases
      and 6 (3.3%) had clonal chromosomal aberrations. Two hundred and sixty-one
      patients were followed up over 12 months with a median of 60 months (range from
      12 to 300 months). Seventeen cases (6.5%) evolved into marrow fibrosis (MF) and
      one case into polycythemia vera (PV). One case evolved into PV 6 years and then
      MF 20 years after diagnosis of ET. Three cases developed acute monocyte leukemia
      (M5), myelodysplastic syndrome (MDS) and multiple myeloma (MM), respectively.
      CONCLUSIONS: ET is a chronic myeloproliferative disorder characterized
      predominantly by thrombocytosis and hemorrhage. The percentage of asymptomatic
      cases is high. The prognoses for most cases were good with a few cases may evolve
      into MF.

PMID- 19175984
TI  - [Leukemia cell surface expression of E-cadherin and its correlation with membrane
      localization of beta-catenin].
AB  - OBJECTIVE: To investigate the expression of cell surface E-cadherin in leukemia
      cell and the correlation of cell membrane localization of beta-catenin with E
      cadherin expression. METHODS: Bone marrow samples from 46 patients with acute
      leukemia and 17 normal donors were analyzed. Cell surface expression of E
      cadherin and membrane localization of beta-catenin were labeled by
      immunofluorescence and analyzed with a laser scanning confocal fluorescence
      microscope in 14 specimens. RESULTS: Cell surface E-cadherin expression level was
      significantly lower in leukemia cells (with the median fluorescent intensity of
      16.78) than in normal hematopoietic progenitors (26.03). Correlation analysis
      showed that cell membrane localization of beta-catenin was correlated with E
      cadherin expression (r = 0.74, P = 0.002). After E-cadherin was induced to
      express in leukemic cell by 5-Aza-CdR, membranous expression of beta-catenin was
      elevated while the nuclear expression reduced, indicating that E-cadherin
      mediated adhesions could recruit beta-catenin to cell membrane. CONCLUSION: The
      loss of E-cadherin in leukemia cells may result in beta-catenin translocating to
      the nuclear and transcriptional activation of its target genes.

PMID- 19175985
TI  - [Expression and significance of BLyS/April in patients with acute idiopathic
      thrombocytopenic purpura].
AB  - OBJECTIVE: To investigate the roles of B-lymphocyte stimulator/ a proliferation
      inducing ligand (BLyS/April) in immunological pathogenesis of idiopathic
      thrombocytopenic purpura (ITP). METHODS: Thirty ITP children and 30 age-matched
      healthy children were studied. Reverse-transcription PCR (RT-PCR) and real-time
      PCR were used to evaluate the mRNA levels of BLyS/ April, receptors for
      BLyS/April (BR3, BCMA and TACI) and cytokines in ITP patients. Flow cytometry was
      performed to measure relative mean fluorescence intensity (relative MFI) for
      platelet-associated immunoglobulin G (PAIgG). RESULTS: (1) The transcription
      levels of BLyS/April in monocytes/macrophage [(8.30 +/- 2.31) x 10(-1) and (7.51
      +/- 1.93) x 10(-3), respectively] were significantly up-regulated in acute ITP
      compared with that in healthy controls [(3.95 +/- 1.04) x 10(-1) and (3.08 +/-
      0.82) x 10(-3), respectively] (P < 0.0.1). (2) Expression levels of the
      BLyS/April receptors BR3, BCMA and TACI mRNA were remarkably raised during acute
      phase of ITP (P < 0.01). (3) The mRNA levels of cytokines, including IL-4, IL-5,
      IL-6, IL-10 and IL-15, were significantly higher in acute phase ITP than in
      healthy controls (P < 0.01). (4) The mRNA levels of IL-10 and IFN-alpha were
      significantly elevated in acute phase of ITP. (5) Relative MFI of acute phase ITP
      patients (67.4 +/- 28.1) was higher than that in healthy controls (19.5 +/- 8.5)
      (P < 0.01), and there was a significant positive correlation between relative MFI
      and BLyS/April as well as their receptors (BR3, BCMA and TACI) (r = 0.56, 0.53,
      0.62, 0.70, 0.45, respectively, P < 0.01), relative MFI in ITP patients decreased
      after treatment. CONCLUSION: Over-expression of BLyS/April may be one of factors
      contributed to the immunological dysfunction in ITP.

PMID- 19175986
TI  - [Mechanism of synergistic anti-tumor effect of PH II -7 with doxorubicin on multi
      drug resistant HL-60/ADR cells].
AB  - OBJECTIVE: To study the synergistic mechanism between PH II -7 and doxorubicin
      against multi-drug resistant HL-60/ADR cells and its parent HL-60 cells. METHODS:
      The anti-tumor activity of doxorubicin alone and combined with PH II -7 were
      measured by MTT assay. RNA was extracted from the cells treated with PH II -7 for
      different times or doses then the expression of MRP gene was measured by RT-PCR.
      Confocal laser scanning microscopy and FACS were used to detect the intracellular
      cumulation of doxorubicin in PH II -7 treated HL-60 and HL-60/ADR cells. RESULTS:
      PH II -7 has anti-tumor effect with IC50 of (0.83 +/- 0.08) micromol/L and (1.74
      +/- 0.56) micromol/L for HL-60 and HL-60/ADR, respectively. It could potentiate
      the anti-tumor effect of doxorubicin with CDI of 0.7 and 0.43 for HL-60 and HL
      60/ADR, respectively. PH II -7 and doxorubicin act synergistically in inhibiting
      the proliferation of HL-60 and HL-60/ADR cells and down-regulating the expression
      of MRP gene in a dose and time dependent manner. PH II -7 restored the
      intracellular cumulation of doxorubicin in HL-60/ADR cells to 55% of that in HL
      60 cells. CONCLUSION: PH II -7 can significantly hasten the cytotoxicity of
      doxorubicin to HL-60 and HL-60/ADR cells through down-regulating the expression
      of MRP. The synergistic effect was more obvious in HL-60/ADR cells.

PMID- 19175987
TI  - [In vitro study of the effects of CDA-II combined with cAMP on apoptosis
      induction in retinoic acid resistant acute promyelocytic leukemia cells].
AB  - OBJECTIVE: To investigate the effects of CDA-II alone or combined with cAMP on
      the retinoic acid (RA)-resistant acute promyelocytic leukemia (APL) cells.
      METHODS: The RA-resistant cell line NB4-R2 was used as an in vitro model and
      treated with CDA-II alone or in combination with cAMP. Cell apoptosis was
      assessed by morphology observation, distribution of cellular DNA contents and sub
      G1 cell population. The level of Bcl-2 was detected by flow cytometry, DNA
      "ladder" was detected by agarose-electrophoresis. RESULTS: CDA-II could induce
      NB4-R2 cell apoptosis through decreasing the level of cellular anti-apoptotic
      protein Bcl-2. cAMP could significantly enhance the role of CDA-II. Bcl-2
      positive cell rates decreased to (15.1 +/- 4.8)% and (7.3 +/- 2.9)% in NB4-R2
      cells treated with 1 mg/ml CDA-II plus 100 micromol/L cAMP for 48 h and 72 h,
      respectively. While 100 micromol/L of cAMP could decrease Bcl-2 positive NB4-R2
      cells from (92.0 +/- 0.6)% to (75.3 +/- 2.0)%. CONCLUSIONS: CDA-II combined with
      cAMP could exert potent apoptotic effect on RA-resistant APL cells.

PMID- 19175988
TI  - [Inhibitory effect of Rnai on AML1 -ETO fusion gene expression in leukemia
      cells].
AB  - OBJECTIVE: By inhibiting AML1 -ETO fusion gene expression in Kasumi-1 cells with
      RNAi, to investigate the changes in cell proliferation and cell cycle. METHODS:
      The small interference RNAs (siRNAs) specifically targeting the AML1 -ETO fusion
      gene were synthesized in vitro and transfected into Kasumi-1 cells by
      electroporation, the non-specific siRNAs transfected cells were taken as control.
      EGFP plasmid was transfected into Kasumi-1 cell and the transfection efficiency
      was detected by FCM. Inhibitory effect of siRNAs were detected by real-time RT
      PCR and Western blots. Cell proliferation was measured by CCK-8 assay. DNA
      content was detected by PI assay. RESULTS: The transfection efficiency was 44.5%.
      The AML1 -ETO specific siRNAs inhibited AML1 -ETO expression at both mRNA and
      protein levels. The cell proliferation rate in siRNAs treated group was lower
      than that in control group 72 h after transfection [(47.90 +/- 0.02)% vs (66.90
      +/- 0.08)% , P < 0.05]. The cell cycle was blocked at G1 phase 72 h after siRNAs
      treatment, the cell proportion in G1 phase being 38.3% and 31.6% in control
      group, while in G2/M phase being 1.8% and 2.4% respectively. CONCLUSIONS: The
      synthesized siRNAs can inhibit AML1 -ETO fusion gene expression. AML1 -ETO
      specific siRNA induced the decline of AML1 -ETO fusion protein in Kasumi-1 cell,
      and then caused the cell cycle blocked in G1 stage and eventually inhibited the
      cell proliferation.

PMID- 19175989
TI  - [Expression of JAK2V617F and MPLW515L/K mutation in 30 suspected cases of early
      myeloproliferative disorders].
AB  - OBJECTIVE: To investigate the prevalence of JAK2V617F and MPLW515L/K mutation in
      patients with slightly elevated platelets (BPC) or hemoglobin (Hb) not meeting
      the criteria of polycythemia vera (PV) or essential thrombocythemia (ET).
      METHODS: Genomic DNA from bone marrow or blood mononuclear cells was screened
      with allele specific polymerase chain reaction (AS-PCR) for JAK2V617F and
      MPLW515L/K mutation. The history of thrombosis was assessed retrospectively by
      patients files. RESULTS: Of 30 patients, 14 (46.7%) were positive for the
      JAK2V617F mutation, none of them had the MPLW515L/ K. Five of these 14 patients
      had a history of thrombosis. Follow-up results were available in 22 patients.
      Among them, 12 patients with JAK2V617F mutation turned out to be MPD in 6-24
      months; only 2 out of 10 patients without this mutation evolved to MPD.
      CONCLUSION: JAK2V617F mutation could be one of the diagnosis criteria of early
      MPD. No MPLW515L/K expression was found in early MPD.

PMID- 19175990
TI  - [In vitro expansion of megakaryocyte progenitor cells from human placenta CD133+
      cells].
AB  - OBJECTIVE: To study the expansion potential of megakaryocyte progenitor cells
      (MPC) from human placenta tissue CD133+ (PT-CD133+) cells. METHODS: PT-CD133+
      cells were purified from mononuclear cells (MNC) by magnetic activated cell
      sorting (MACS) and seeded in serum-free liquid culture medium supplemented with
      thrombopoietin (TPO), interleukin-3 (IL-3), and stem cell factor (SCF) to expand
      MPC. At day 7, 10 and 14, the total cell number was counted and the dynamic
      changes of CD133, CD34, and CD41 antigens expression during ex-vivo expansion
      were analyzed by flow cytometry (FCM). PT-CD133+ cells at different expansion
      time were collected and cultured in collagen semisolid medium for colony forming
      units-megakaryocyte (CFU-MK) assay. RESULTS: PT-CD133+ cells could be optimally
      expanded at day 7 by 13 +/- 2 fold increase in serum-free liquid culture systems
      and the total cell number was expanded by 160 fold at day 14. With the expansion
      time going on, the expression of CD133, CD34 decreased and that of CD41
      increased. The expanded megakaryocytes were immature and no sign of platelet
      formation. Both PT-CD133+ cells before and after expansion could form CFU-MK, the
      total number of CFU-MK peaked at day 10 of expansion by 54 +/- 10 fold increase.
      CONCLUSION: Human PT-CD133+ cells have a high capacity of MPC expansion, 10 days
      culture could give rise to the maximum number of CFU-MK.

PMID- 19175992
TI  - ?

PMID- 19175991
TI  - [Clinical analysis of amphotericin B in the treatment of invasive fungal
      infections in 121 patients with hematologic diseases].
AB  - OBJECTIVE: To observe the efficacy and safety of amphotericin B for treatment of
      invasive fungal infections (IFI) in patients with hematologic diseases. METHODS:
      121 patients were given amphotericin B 5 -50 mg/d for 5 - 101 d with a median of
      19 d. RESULTS: The clinical efficacy rate was 67.3%, and fungal elimination rate
      66.7%. The adverse events included rigor and fever, hypokalaemia, hepatic damage,
      nephrotoxicity, nausea and vomiting, phlebitis and teeter. CONCLUSION:
      Amphotericin B is still a high-efficiency drug in the treatment of IFI, although
      it has many side effects. With monitoring of hepatic and renal function, it is
      still a relatively safe and effective drug.

PMID- 19175994
TI  - ?

PMID- 19175993
TI  - [Preliminary study of diagnosis of patients with myelodysplastic syndromes by
      routine laboratory parameters].
AB  - OBJECTIVE: To explore the value of routine laboratory parameters in diagnosis of
      myelodysplastic syndromes (MDS) and differential diagnosis of patients with
      hypoplastic MDS from chronic aplastic anemia (CAA) for providing reference
      standard for primary hospitals. METHODS: The laboratory parameters at diagnosis
      of 152 MDS patients with less than 0.05 bone marrow blasts and 86 CAA patients
      were retrospectively analyzed. RESULTS: There were significant differences
      between MDS and CAA in Hb, red cell distribution width-coefficient variation (RDW
      CV), immature reticulocyte fraction (IRF), BPC, the ratio of G1 (the sum
      percentage of myeloblast and promyelocyte) to G2 (the sum percentage of
      neutrophilic myelocyte and metamyelocyte) (Ratio G), the ratio of El (the sum
      percentage of proerythroblast and early erythroblast) to E2 (the sum percentage
      of intermediate erythroblast and late erythroblast) (Ratio E), megakaryocyte
      count (Meg), erythroblast PAS, neutrophil alkaline phosphatase (N-ALP), and
      serous levels of indirect bilirubin (IBIL), lactose dehydrogenase (LDH), folic
      acid (FA), VitB12 and ferritin. Chromosome abnormalities were found in 74 MDS
      patients (48.7%) but in none of CAA patients (P < 0.001). Furthermore, for
      differentiating MDS with less than 0.05 blasts from CAA, the sensitivity and
      specificity of combination of Meg, PAS, and IBIL level was 89.1% and 92.7%, the
      Youden index (gamma) was 0.818. Moreover, in the seven hypoplastic MDS cases,
      BPC, myeloblast percentage, Ratio G, Meg, erythroblast PAS and FA were
      statistically different from those of CAA; the sensitivity and specificity of
      combination of PAS and BPC was 85.7% and 100%, the gamma was 0.857; the
      sensitivity and specificity combination of Ratio G, Meg PAS was 85.7% and 98.8%
      respectively, the gamma was 0.845. CONCLUSION: The routine laboratory parameters,
      especially BPC, Meg, Ratio G, PAS, IBIL may be helpful for the diagnosis of MDS
      and differential diagnosis of hypoplastic MDS from CAA.

PMID- 19175995
TI  - ?

PMID- 19175996
TI  - ?

PMID- 19175998
TI  - ?

PMID- 19175997
TI  - ?

PMID- 19175999
TI  - ?

PMID- 19176000
TI  - ?

PMID- 19176001
TI  - ?

PMID- 19176002
TI  - ?

PMID- 19176003
TI  - [To standardize the treatment regimen so as to improve the therapeutic outcome of
      aplastic anemia].

PMID- 19176004
TI  - [An analysis of prognostic factors in 80 myelodysplastic syndrome].
AB  - OBJECTIVE: To investigate the WHO classification, clinical and hematological
      features and risk group of International Prognostic Scoring System (IPSS) in
      patients with myelodysplastic syndrome (MDS). METHODS: The diagnosis and
      classification of MDS patients were defined according to the WHO classification.
      The clinical manifestations, hemogram, bone marrow biopsy and prognosis were
      retrospectively analyzed. RESULTS: The median age at diagnosis of MDS was 47 yrs
      being younger than that in some foreign reports. The frequency of abnormal
      karyotype was 35.14% and +8 was the most frequent abnormal karyotype in our
      study. Eleven of 74 patients transformed into leukemia. Univariate analysis
      showed that age, chromosome abnormality, percentage of bone marrow blast cells
      and number of cytopenias were significantly related to prognosis. There was a
      statistical difference in cum survival rate between IPSS subcategories (P < 0.05)
      except that between low- and intermediate I-risk subcategory (P > 0.05). There
      were statistical differences for refractory anemia (RA) vs RA with excess blast
      (RAEB), refractory cytopenias with multilineage dysplasia (RCMD) vs RAEB and RAEB
      I vs RAEB-II (P < 0.05). CONCLUSIONS: There were differences in age of disease
      onset, distribution of WHO, sub-classification and abnormal karyotype in this
      cohort of MDS patients as compared with those in Europe and Japan. It is helpful
      in diagnosis, treatment and prognosis to divide RAEB into RAEB-I and RAEB-II.
      IPSS was well applicable in Chinese MDS patients.

PMID- 19176006
TI  - [The impact of immunosuppressive therapy on genetic instabilities of bone marrow
      hematopoietic cells in patients with aplastic anemia].
AB  - OBJECTIVE: To investigate the impact of immunosuppressive therapy (IST) on
      genetic instabilities of bone marrow hematopoietic cells (BMHCs) in patients with
      aplastic anemia (AA). METHODS: Comet assay as used to detect genetic
      instabilities of hematopoietic cells from patients, and the percent of DNA in
      comet tail (TDNA), tail length (TL), tail moment (TM), olive tail moment (OTM)
      and the rate of comet cells were measured. BMHCs from AA patients were examined
      with comet assay before and after IST, and the results were compared with those
      from controls. RESULTS: Comet parameters from 91 AA patients including TDNA, TL,
      TM, OTM comet cell percentage were (5.0 +/- 4.0)%, 11.3 +/- 7.2, 1.7 +/- 2.0, 1.5
      +/- 1.4, (16.8 +/- 13.7)%, respectively, which were significantly higher than
      those from control group (P < 0.05). There were statistical differences between
      the comet parameters of severe AA (SAA)/non-SAA (NSAA) and those of control group
      (P < 0.05), but no difference in the comet parameters between SAA and NSAA
      patients (P > 0.05). The TDNA, TL, TM, OTM and comet cells percentage were (4.4
      +/- 3.6)%, 10.4 +/- 7.5, 1.4 +/- 1.6, 1.3 +/- 1.4 and (20.2 +/- 21.2)%,
      respectively at 3 months after IST in 53 SAA patients and were (3.7 +/- 3.3)%,
      10.0 +/- 7.2, 1.2 +/- 1.8, 1.1 +/- 1.3 and (18.5 +/- 19.0)% respectively at 6
      months after IST in 30 SAA patients, being no statistical difference from those
      of 58 SAA patients before IST (P values were all > 0.05). CONCLUSION: BMHCs of AA
      had inherent genetic instabilities which were not increased by recent IST. It
      indicated that there was no correlation between IST and the development of clonal
      hematologic disorders in AA.

PMID- 19176008
TI  - [Study on the dendritic cell subsets in peripheral blood and its relationship
      with the expressions of T-bet and GATA-3 in lymphocytes in severe aplastic
      anemia].
AB  - OBJECTIVE: To investigate the relationship between the dendritic cell (DC)
      subsets and transcriptive factors, T-bet, GATA-3, and immune imbalance in
      acquired severe aplastic anemia (SAA). METHODS: The DC1 (HLA-DR+Lin-CD11c+) and
      DC2 (HLA-DR+Lin-CD123+) in peripheral blood mononuclear cells (PBMNC) were
      measured with flow cytometry (FCM), the expressions of T-bet mRNA and GATA-3 mRNA
      in PBMNC with semiquantitative RT-PCR and the plasma level of IFN gamma and IL-4
      with ELISA in 29 SAA patients and 16 healthy controls. RESULTS: The percentages
      of DC1 in PBMNC were (0.44 +/- 0.24)% and (0.73 +/- 0.30)% in untreated and
      recovered SAA patients respectively, both were higher than that in controls (0.29
      +/- 0.10)% (P < 0.05). The percentage of DC2 in the untreated cases was lower
      than that of recovered ones or controls [(0.18 +/- 0.14)% vs (0.28 +/- 0.20)% and
      (0.29 +/- 0.13)%] (P < 0.05). DC1/DC2 ratios were 3.45 +/- 2.71 and 2.90 +/- 0.95
      in untreated and recovered groups respectively, both were higher than that in
      controls (1.15 +/- 0.56) (P < 0.05). No statistic difference in DC1/DC2 ratio was
      found between untreated and recovered patients (P < 0.05). The relative mRNA
      expression levels of transcriptive factor T-bet were 0.37 +/- 0.07, 0.20 +/- 0.07
      and 0.17 +/- 0.05 in the above 3 groups, respectively, untreated group being
      higher than that of recovered group or healthy controls (P < 0.05). There was no
      statistic difference of GATA-3 expression among the 3 groups (P > 0.05). T
      bet/GATA-3 ratio was 0.72 +/- 0.13 in untreated group, being higher than that of
      recovered group (0.33 +/- 0.08) or controls (0.35 +/- 0.11). The plasma level of
      IFN gamma in the untreated group was (50.9 +/- 1.1) ng/L, which was higher than
      that of recovered group [(49.7 +/- 0.9) ng/L] or controls [(49.7 +/- 0.7) ng/L].
      There was significant positive correlations between T-bet and DC1/DC2 ratio (r =
      0.445, P < 0.01), as well as between T-bet and IFN gamma (r = 0.402, P < 0.01).
      CONCLUSION: Either DC1/DC2 or T-bet/GATA-3 ratio might become an index to
      estimate immune imbalance. High-expressed T-bet was related to the progress of
      SAA. In patients with SAA, DC1/DC2 ratio returns to normal range later than that
      of routine blood test does, indicating that immunosuppressive therapy should not
      be withdrawn too earlier.

PMID- 19176009
TI  - [In vitro effect of bortezomib alone or in combination with harringtonine or
      arsenic trioxide on proliferation and apoptosis of multidrug resistant leukemia
      cells].
AB  - OBJECTIVE: To investigate the effect of bortezomib alone or combined with
      harringtonine (HT) or arsenic trioxide (As2O3) on the proliferation capacity and
      apoptosis of HL-60/ADM cell line and fresh cells from refractory/relapse acute
      leukemia patients. METHODS: HL-60/ADM cells or refractory/relapse leukemia cells
      were incubated with bortezomib at different doses alone and in combination with
      HT or As2O3. The proliferation capacity was observed by MTT assay, cell apoptosis
      by fluorescence microscopy and flow cytometry. Intracellular concentration of
      daunorubicin (DNR) was determined by flow cytometry. RESULTS: In bortezomib
      treated HL-60/ADM cells, the proliferation inhibition rate and apoptotic cells
      increased in a time- and dose-dependent manner. 40 nmol/L bortezomib could
      maximally inhibit the proliferation of HL-60/ADM cells at 48 hours. 15 micromol/L
      As2O3 or 752 nmol/L HT combined with different doses of bortezomib could inhibit
      proliferation and induce apoptosis of HL-60/ADM cells. The As2O3 plus bortezomib
      or HT plus bortezomib showed a greater anticancer efficacy than either of the
      drugs alone (P < 0.05, P < 0.01). Bortezomib (10 nmol/L) could markedly enhance
      the intracellular accumulation of DNR in HL-60/ADM cells (P < 0.05). CONCLUSIONS:
      Bortezomib can inhibit proliferation and induce apoptosis of HL-60/ADM cells and
      fresh refractory/relapse acute leukemia cells, especially combined with HT or
      As2O3.

PMID- 19176010
TI  - [Correlation of FLT3 gene expression level and internal tandem duplication
      mutation in acute myeloid leukemia and its clinical significance].
AB  - OBJECTIVE: To evaluate the prevalence of FLT3 gene expression and internal tandem
      duplication (ITD) mutation in acute myeloid leukemia (AML) patients and its
      clinical significance. METHODS: The expression level of FLT3 mRNA was detected
      with real-time quantitative RT-PCR (RQ-PCR) technique in 152 bone marrow samples
      from 129 AML patients. The ITD of the FLT3 gene (FLT3/ITD) was detected in 75 de
      novo AML patients by reverse transcription polymerase chain reaction (RT-PCR).
      RESULTS: The expression levels of FLT3 mRNA was 0.0020(0.0006 - 0.0040) in normal
      controls, and 0.1041 (0 - 33.8736) in 80 de novo AML patients (P = 0.001).
      FLT3/ITDs were found in 11 (14.7%) of 75 de novo AML patients. The FLT3
      expression levels in patients with FLT3/ITD were 0.0297 to 33.8736 with a median
      level of 0.2200, and in those without FLT3/ITD were 0 to 26.2200 with a median
      level of 0.0975. The FLT3 expression levels in the former patients were higher
      than that in the latter ones, but there was no statistical significance (P =
      0.093). The complete remission (CR) rate was lower in acute promyelocytic
      leukemia (APL) patients with FLT3/ITD than in APL patients without FLT3/ITD (P =
      0.015). In de novo AML other than APL patients without FLT3/ITD, the CR rate was
      lower in patients with higher levels of FLT3 expression (expression level > 0.04,
      CR rate 37.5%) than those with lower levels of FLT3 expression (expression level
      < 0.04, CR rate 100%). On follow-up of 20 patients, the FLT3 expression level was
      decreased at least one logarithm degree when they got CR, but it was no
      significant change in non-remission patients. CONCLUSIONS: Quantification of FLT3
      mRNA expression level and detection of FLT3/ITD in AML patients may serve as an
      index for evaluating therapeutic efficacy, predicting prognosis, and monitoring
      minimal residual disease.

PMID- 19176011
TI  - [Expression of cyclin A in childhood acute leukemia and its significance].
AB  - OBJECTIVE: To investigate the expression of cyclin A protein in childhood acute
      leukemia (AL) and its significance. METHODS: By using Western blotting analysis,
      cyclin A protein in bone marrow mononuclear cells from 47 newly diagnosed AL
      children and 33 non-hematological malignancy children was detected. RESULTS: The
      expression of cyclin A in AL group (0.38 +/- 0.20) was higher than that in
      control group (0.03 +/- 0.15) (P < 0.01). The expression of cyclin A in high risk
      acute lymphocyte leukemia (ALL) group (HR-ALL) (0.62 +/- 0.38) was higher than
      that in standard risk ALL group (SR-ALL) (0.33 +/- 0.33) (P < 0.05). The
      expression of cyclin A in WBC > or = 50 x 10(9)/L group and in WBC < 50 x 10(9)/L
      group was (0.64 +/- 0.36) and (0.39 +/- 0.38), respectively (P < 0.05). Eight
      (44.4%) out of 18 patients with positive cyclin A expression achieved complete
      remission (CR). The CR rate was lower than that of patients with negative cyclin
      A expression (100%) (P < 0.01). CONCLUSIONS: The higher expression of cyclin A
      may predict a poor prognosis for childhood ALL.

PMID- 19176012
TI  - [Expression of transcription factor LYL1 in leukemia and its possible role in
      leukemogenesis].
AB  - OBJECTIVE: To study the expression of transcription factor LYL1 in leukemia and
      its possible role in leukemogenesis. METHODS: Fluorescence real time quantitative
      polymerase chain reaction was used to detect the expression levels of LYL1 in
      leukemias. Specific siRNA was used to silence the expression of LYL1 in K562
      cells. RESULTS: Compared to CD34 positive cells from normal bone marrow, the
      expression of LYL1 was significantly elevated in patients with acute myeloid
      leukemia (AML) and acute lymphoblastic leukemia (ALL). LYL1 expression was higher
      in chronic myeloid leukemia (CML) in blastic crisis than that in chronic phase
      (7.831 vs 1.672, P < 0.01). LYL1 expression in AML in complete remission (CR) was
      down-regulated as compared with that of un-remission patients (1.400 vs 9.985, P
      < 0.01). Down-regulation of endogenous expression of LYL1 in K562 cells by a
      combination of three specific siRNA could inhibit cellular growth and
      clonogenicity to some extent. CONCLUSION: Over-expression of LYL1 is highly
      associated with AML as well as ALL. RNA interference targeting specific oncogenes
      such as LYL1 is potentially useful in the treatment of hematological
      malignancies.

PMID- 19176013
TI  - [Expression of PML-RAR alpha fusion transcripts detection by using RQ-PCR].
AB  - OBJECTIVE: To establish the real time quantitative PCR (RQ-PCR) assay according
      to 'Europe Against Cancer' (EAC) program and analyze the results of detection and
      quantification of different PML-RAR alpha transcript isoforms in patients with
      acute promyelocytic leukemia (APL). METHODS: Three RQ-PCR systems were performed
      to detect the most frequent PML-RAR alpha transcripts (L-form, S-form and V-form)
      in 30 APL patients and the RQ-PCR end-point products were identified by
      electrophoresis. RESULTS: S-form RQ-PCR system could amplify positive signals of
      three isoforms in all of 30 cases, and V-form RQ-PCR system could do so in both L
      form and V-form positive cases, however, L-form RQ-PCR system could only do so in
      L-form-positive cases. Electrophoresis and sequencing of end-point products
      amplified by S-form RQ-PCR system revealed three bands in each of L-form (621 bp,
      477 bp and 218 bp) and V-form (567 bp, 423 bp and 218 bp) positive patients
      samples. CONCLUSIONS: RQ-PCR, sensitive and reliable, can be used for monitoring
      the minimal residual disease in APL patients, however, its results should be
      interpreted carefully if it is used for detection of PML-RAR alpha fusion
      transcripts prospectively.

PMID- 19176014
TI  - [Prevalence and clinical significance of FLT3 mutations in acute promyelocytic
      leukemia].
AB  - OBJECTIVE: To evaluate the prevalence of Fms-Like tyrosine kinase 3 (FLT3)
      mutations including internal tandem duplication (ITD) of juxtamembrane region and
      point mutation in the second tyrosine kinase domain (TKD) in acute promyelocytic
      leukemia (APL) and its clinical significance. METHODS: Bone marrow mononuclear
      cells from 160 newly diagnosed APL patients were analyzed. Polymerase chain
      reaction (PCR) was used to detect FLT3-ITD mutations, FLT3-ITD positive samples
      were further analyzed for the ITD allelic ratio (ITD-AR, mutant-wild type ratio).
      The FLT3-TKD mutation was analyzed by PCR amplification of exon 20 followed by
      EcoR V digestion and sequencing. RESULTS: Out of 160 patients, 30 (18.75%)
      patients were FLT3-ITD positive, 17 (10.62%) were FLT3-TKD positive, 2 had both
      of mutations. The initial WBC count and the ratio of short type PML-RAR alpha
      isoforms in FLT3-ITD positive and FLT3-TKD positive patients were all higher than
      that in patients with wild-type FLT3 (FLT3-wt) (P < 0.05). For FLT3-ITD positive
      patients, the incidences of retinoic acid syndrome (RAS) and disseminated
      intravascular coagulation (DIC) were 41.7% and 65.4%, respectively, being higher
      than that of FLT3-wt patients, while their complete remission (CR) rate was lower
      (69.2% vs 90.3%, P < 0.05). For FLT3-TKD positive patients, the incidence of RAS,
      DIC and CR rate were not significantly different from that of FLT3-wt patients (P
      > 0.05). FLT3-ITD positive patients had a shorter overall survival (OS) (P <
      0.05), but not disease-free survival (DFS) (P > 0.05) as compared with FLT3-wt
      patients. There was no significant difference in either OS or DFS between FLT3
      TKD positive and FLT3-wt patients. The ITD-AR of 30 FLT3-ITD positive patients
      varied from 0.11 to 6.55 with a median of 1.0. The initial WBC count, incidence
      of RAS and DIC, CR rate were not significantly different between the patients
      with ITD-AR greater than 1.0 and lower than 1.0 (P > 0.05). CONCLUSIONS: FLT3
      mutations (FLT3-ITD or FLT3-TKD) are frequently identified in patients with newly
      diagnosed APL, both mutations are associated with higher initial WBC and short
      type PML-RAR alpha isoforms. FLT3-ITD mutation is more frequent than FLT3-TKD
      mutation, and predicts a poorer prognosis, whereas FLT3-TKD mutation does not
      show the same unfavorable prognostic effect on APL patients.

PMID- 19176030
TI  - [The role of CD147 in the proliferation, activation and chemotaxis of Jurkat cell
      induced by cyclophilin A].
AB  - OBJECTIVE: To investigate the role of CD147 in the proliferation, activation and
      chemotaxis of Jurkat cell induced by cyclophilin A (CyPA). METHODS: CD147 mRNA
      and protein level siRNA transfected Jurkat cells were identified by RT-PCR and
      Western blot respectively. Jurkat cell, Jurkat-vector cell and Jurkat-CD147 siRNA
      cells were treated with different concentrations of CyPA (0.01 nmol/L, 0.1
      nmol/L, 1 nmol/L, 10 nmol/L) or PBS for 24 h and 48 h. Proliferation level was
      detected by MTT assay. CD25 was measured by flow cytometry. Transwell chamber was
      used to detect the chemotaxis. The effect of CyPA on the adhesive potential of
      Jurkat cell was studied by cell-matrix adhesion assay. RESULTS: CD147 mRNA and
      protein level siRNA transfected cells were decreased significantly than that of
      control cells. CyPA stimulated the proliferation of Jurkat cell in a dose
      dependent manner, its effect peaked at 10 nmol/L CyPA. Blockage of CD147
      expression decreased the proliferation level of Jurkat cell induced by CyPA. CyPA
      increased the activation rate of Jurkat cell, and blockage CD147 expression
      decreased the activation rate of the cell induced by CypA. CyPA showed a
      chemotactic activity on Jurkat cell, the chemotaxis index being 2.32, and the
      chemotactic ability was decreased after inhibition of CD147 expression. CyPA had
      no effect on adhesion of Jurkat cell to extracellular matrix. CONCLUSION: CD147
      plays a role in the proliferation, activation and chemotaxis of Jurkat cell
      induced by CyPA.

PMID- 19176031
TI  - [Analysis of c-kit and JAK2 gene mutations in t(8;21) acute myeloid leukemia].
AB  - OBJECTIVE: To evaluate the prevalence of c-kit and JAK2 gene mutations in protein
      tyrosine kinase (PTK) family in adult t(8;21) acute myeloid leukemia (AML) and
      their implications. METHODS: Genomic DNAs from 78 t(8;21) AML patients were
      screened for mutated c-kit (mutKIT) in exon 8 and 17 by PCR and sequencing. JAK2
      V617F mutation screening was processed by allele-specific PCR. RESULTS: (1) Among
      78 t(8;21) AML patients, 27 (34.6%) had muc-kit/JAK2 and 6 (7.7%) had JAK2 V617F,
      and none had both. (2) Peripheral WBC count was higher in mutKIT/JAK2 V617F
      patients than in wide-type c-kit/JAK2 (wtKIT/JAK2) patients ?[(36.2 +/- 37.7) x
      10(9)/L vs (21.7 +/- 21.1) x 10(9)/L?] (P < 0.05). There was no significant
      difference in hemoglobin level, platelet counts, percentage of blast cell in bone
      marrow, CD117 expression level, the age of onset and gender between the two
      groups. Peripheral WBC count was higher in mutKIT patients ?[(38.8 +/- 40.7) x
      10(9)/L?] than in wtKIT patients ?[(22.0 +/- 20.4) x 10(9)/L?] (P < 0.05). (3)
      Complete remission (CR) rates between patients with mutkit/JAK2 V617F and with
      wtKIT/JAK2 were similar (69.6% vs 80.0%, P > 0.05), but the 2 year continuous CR
      (CCR) rate was lower in patients with mutKIT/JAK2 V617F (26.7% vs 56.1%, P <
      0.05). However, there was no significant difference in OS between mutKIT/JAK2
      V617F and wtKIT/JAK2 patients (34.8% vs 58.6%, P > 0.05). CONCLUSIONS: Occurrence
      of c-kit and JAK2 gene mutations especially c-kit mutation is common in t(8;21)
      AML patients, and is associated with higher WBC. These mutations confer higher
      relapse risk and predict poor prognosis.

PMID- 19176032
TI  - [Inhibitory effect of valproic acid on cell cycle of Kasumi-1 cell line and its
      mechanism].
AB  - OBJECTIVE: To investigate the influence of valproic acid (VPA), a histone
      deacetylase (HDAC) inhibitor, on cell cycle of Kasumi-1 cells, and explore its
      molecular mechanism. METHODS: Kasumi-1 cells were treated with VPA at different
      concentration and different time cell cycle changes were analyzed by flow
      cytometry. Cyclin D1 and p21(WAF1/CIP) gene, a cyclin-dependent kinase inhibitor,
      were determined by semi-quantitative RT-PCR and Western blot. RESULTS: (1) VPA
      blocked the Kasumi-1 cells in G(0)/G(1) phase. (2) Compared with control group, 3
      mmol/L VPA treated Kasumi-1 cells for different times caused their mRNA
      expression of cyclin D1 decreased. Treated with VPA at different concentration
      for 3 days, the mRNA expression decreased in a dose-dependent manner. (3) VPA
      induced p21(WAF1/CIP) mRNA expression increased in a time- and dose-dependent
      manner. The p21(WAF1/CIP) protein increased with increasing concentration of VPA
      at day 3. The p21(WAF1/CIP) protein significantly increased with 3 mmol/L VPA
      treatment for 2 d (2.498 +/- 0.240). CONCLUSION: VPA can arrest Kasumi-1 cell in
      G(0)/G(1) phase through the regulation of cyclin D1 and p21(WAF1/CIP).

PMID- 19176033
TI  - [Molecular regulation of KIR3DL1 gene expression by transcription factor E2F1].
AB  - OBJECTIVE: To study the role of transcription factor E2F1 in the transcription of
      KIR3DL1 promoter, and to identify its molecular mechanism of regulation of
      KIR3DL1 gene expression. METHODS: The mutant promoter fragment of KIR3DL1 gene
      was amplified from genomic DNA of K562 cells by PCR. The PCR product was cloned
      into pGL3-basic reporter vector to construct KIR3DL1 promoter-luciferase reporter
      plasmid (PLRP). The binding of E2F1 to KIR3DL1 promoter was detected by chromatin
      immunoprecipitation (CHIP) assays. The KIR3DL1 PLRP construction was transfected
      into K562 cells using cationic liposome SuperFect. The binding of E2F1 to the
      construction was detected by CHIP assays and reporter activity was quantitated by
      the dual-luciferase reporter assay system. The mammalian expression vector
      containing E2F1 cDNA was co-transfected into K562 cells with wild-type KIR3DL1
      PLR construction and reporter activity was quantitated. RESULTS: The mutant
      KIR3DL1 PLR recombinant was constructed successfully and a naturally point
      mutation (TTTGGCGC-->TTCGGCGC) within a putative E2F1 binding site in the KIR3DL1
      promoter region was authenticated by DNA sequencing. E2F1 absolutely could not
      bind to the mutant KIR3DL1 promoter in K562 cells, but could bind to the wild
      type one in NK-92MI cells. The binding of E2F1 to the mutant KIR3DL1 PLR
      construction was partially reserved, however, its relative luciferase activity
      was decreased by 50% than that of wild-type. On the other hand, when co
      transfected with E2F1 mammalian expression vector, the relative luciferase
      activity of wild-type construction was increased, over 2-fold higher than that of
      control group. CONCLUSION: E2F1 participates in the regulation of the
      transcriptional activation of KIR3DL1 gene. The number of CpG dinucleotide and
      methylation pattern within the E2F1 binding site probably influence the binding
      of E2F1 to target sequence.

PMID- 19176034
TI  - [The effect of recombinant human erythropoietin on the migration of bone marrow
      derived mesenchymal stem cells in vitro].
AB  - OBJECTIVE: To explore the effects of rhEPO on the migration of bone marrow(BM)
      derived mesenchymal stem cells(MSCs) and its probable signal transduction
      mechanism. METHODS: MSC was cultured by classical whole BM adherence method; MSC
      characteristics was identified by multi-differentiation and surface marker (CD90,
      CD133, CD34, CD105). The effect of different concentrations EPO (1, 10, 100, 1000
      IU/ml) on MSCs migration were observed. Then 30 minutes later, MSC were treated
      with signal transduction pathway inhibitors, 50 nmol/L wortmannin, 50 micromol/L
      PD98059, 10 micromol/L U73122, 4 microg/ml Anti EPO-R IgG, 30 micromol/L
      SB203580, 10 mmol/L Staurosporine, 6 nmol/L G06976 and 50 micromol/L Pseudo Z,
      respectively. The efficacy of MSC migration was analyzed by Transwell in vitro
      migration assay. RESULTS: Cultured MSCs had the capacities for osteogenic and
      adipogenic differentiation and highly expressed CD105, CD90 and EPO-R. The
      efficiency of MSC in vitro migration increased gradually in a concentration
      dependent manner with increasing concentration of rhEPO, and the ability peaked
      at a concentration of 100 IU/ml. Furthermore, the migration ability was decreased
      on treated with U73122, Anti EPO-R IgG, Staurosporine, Pseudo Z treatment.
      CONCLUSION: EPO/EPO-R-mediated MSCs migration is related with MAPK, PI-PLC/PKC
      zeta signal pathways, PKC-zeta signal pathway may be of central role for MSCs
      migration.

PMID- 19176035
TI  - [Effect on bcr-abl signaling pathway and the mechanisms of apoptosis induction by
      meisoindigo in K562 cells].
AB  - OBJECTIVE: To investigate the effect of meisoindigo on bcr-abl signaling pathway
      and to explore the mechanism of meisoindigo inducing apoptosis in K562 cells.
      METHODS: Apoptosis and mitochondria membrane potential (MMP) were evaluated by
      flow cytometry. In K562 cells, the expression level of Bcl-2 family members,
      cleaved caspase members, bcr-abl, STAT5 and CRKL were determined by Western blot
      and bcr-abl mRNA expression level was measured by RT-PCR before and after
      meisoindigo treatment. The DNA binding potential of STAT3 and STAT5 was checked
      by electronic mobility shift assay (EMSA). RESULTS: Down-regulation of total and
      phosphorylated bcr-abl protein level in K562 cells was observed when treated with
      20 micromol/L meisoindigo, but its mRNA level was not changed. The expression
      level of phosphorylated STAT5 and CRKL was decreased and the DNA binding
      potential of STAT3 and STAT5 were inhibited in K562 cell after exposure to
      meisoindigo. Exposure to 5 - 20 micromol/L meisoindigo induced apoptosis
      accompanied with activating of caspase 3, 8, 9 and decreasing of MMP in K562
      cells in a dose-dependent manner. The apoptosis was blocked by 50 micromol/L z
      DEVD-fmk, z-IETD-cho, z-LETD-fmk, the specific inhibitors of caspase 3, 8, 9,
      respectively. No change in Bcl-2, Bax and Bid protein expression levels were
      observed before and after meisoindigo inducing apoptosis. CONCLUSION: Meisoindigo
      can inhibit the proliferation of K562 cells by affecting the bcr-abl signaling
      transduction pathway. Meisoindigo induces K562 cell apoptosis through a novel
      caspase dependent pathway in addition to the contribution of mitochondria. The
      Bcl-2 family members are not involved in the apoptosis induction by meisoindigo
      in K562 cells.

PMID- 19176036
TI  - [The impact of CD34(+) cells and T cells subsets in grafts on prognosis of HLA
      identical sibling allogeneic peripheral blood stem cell transplantation].
AB  - OBJECTIVE: To study the influence of CD34(+) and T cells doses in grafts on
      prognosis after HLA-identical sibling allogeneic peripheral blood stem cell
      transplantation (allo-PBSCT). METHODS: Sixty-five patients received HLA-identical
      sibling allo-PBSCT were studied. The numbers of CD34(+), CD3(+), CD3(+)CD4(+) and
      CD3(+)CD8(+) T cells in the grafts were measured by fluorescence-activated cell
      sorting (FACS). The doses of MNC, and the above cells in grafts were calculated
      as per kilogram of recipient's body weight. The patients were divided into high
      dose (HD) or low-dose (LD) groups according to median dose of those cells,
      respectively. Hematopoiesis reconstitution, incidence of graft versus host
      disease (GVHD), transplant-related mortality (TRM), overall survival (OS), and
      disease-free survival (DFS) were analyzed. RESULTS: HD CD34(+) cells
      significantly accelerated neutrophil and platelet reconstitution (P < 0.05).
      There seems a trend toward increasing incidence of grade II approximately IV
      acute GVHD (aGVHD) in HD CD3(+)CD4(+) and CD3(+)CD8(+) T cells groups compared
      with those LD groups (P = 0.089 and 0.098, respectively). The TRM rates were
      significantly higher and OS rates were significantly in HD CD3(+)CD4(+) and
      CD3(+)CD8(+) T cells groups than in LD groups, respectively (both P < 0.05).
      Multivariate analyses showed that CD3(+)CD4(+) and CD3(+)CD8(+) T cells doses in
      grafts were significant risk factors for TRM ?[relative risk (RR) were 13.12 and
      25.90, respectively, both P < 0.05?] and for OS (RR were 3.71 and 3.01,
      respectively, both P < 0.05). The DFS rate was significantly lower in HD
      CD3(+)CD4(+) T cells groups than in LD groups (P < 0.05). Multivariate analyses
      showed that CD3(+)CD4(+) cells dose in grafts was a significant risk factor for
      DFS (RR = 6.91, P = 0.011). CONCLUSIONS: High dose CD34(+) cells in grafts
      significantly accelerate hematopoietic reconstitution. Transfusion of high doses
      CD3(+)CD4(+) and CD3(+)CD8(+) cells increases TRM, but decrease OS or DFS.

PMID- 19176037
TI  - [A retrospective analysis of clinical outcomes in 225 childhood with acute
      lymphoblastic leukemia].
AB  - OBJECTIVE: To retrospectively analyze the outcomes in newly diagnosed children
      with acute lymphoblastic leukemia (ALL). METHODS: Two hundred and twenty-five
      children with ALL (from Jan 2003 to Dec 2006) were divided into high-(HR) and
      standard-risk (SR) groups according to cytomorphology, immunology, cytogenetics
      and molecular biology (MICM) finding. SR patients were treated with conventional
      therapy, while HR patients with additional high-dose (HD) methotrexate (MTX) (5
      g/m(2)) and early mid-dose cytarabine (Ara-C) (1 g/m(2), q 12 h x 3 d). All
      patients took maintenance chemotherapy of MM+VP. Respond rate (RR) and overall
      survival (OS) rate of patients were retrospectively analyzed. RESULTS: The
      probabilities of 3-year and 5-year OS were 79.0% and 72.6%, respectively. The SR
      patients had a remarkably higher 3-year OS (87.6%) than that of HR patients
      (66.1%) (P = 0.002). CONCLUSION: (1) Early intensive therapy with mid-dose Ara-C
      and HD-MTX significantly improves the outcome of HR children with ALL. (2) The
      early intensive therapy in HR patients reduces the incidence of CNSL. (3)
      Periodic intensification and more re-induction therapies in SR patients
      remarkably improves the long-term survival.

PMID- 19176038
TI  - [The influence of bortezomib on HL-60 cell function induced by all-trans retinoic
      acid plus bufalin and its mechanism].
AB  - OBJECTIVE: To investigate changes in the adherent ability, the expression of
      adhesion related proteins Pyk2 and paxillin during HL-60 cells differentiation
      into granulocyte-monocyte induced by low-dose (LD) bufalin in combination with
      all-trans retinoic acid (ATRA), and to explore the effects of bortezomib on
      cellular adhesion and the expression of Pyk2 and paxillin. METHODS: The
      expression of CD11b was detected by flow cytometry, cellular adherence ability by
      MTT assay, and the expressions of Pyk2, paxillin and tubulin by Western blot.
      RESULTS: The combination of 5 nmol/L bufalin and 30 nmol/L ATRA induced HL-60
      cells differentiation in a time-dependent manner, the percentages of CD11b
      positive cells treated for 2 d and 4 d being (20.0 +/- 2.8)% and (75.0 +/- 5.3)%,
      respectively, with the increasing of cellular adherence ability. Meanwhile the
      expressions of Pyk2 and Paxillin were also up-regulated in a time-dependent
      manner. Bortezomib suppressed HL-60 cell adhesion in a dose-dependent manner. At
      concentrations of 1 nmol/L and 10 nmol/L the adherence level were (7.8 +/- 0.1)%
      and (5.3 +/- 0.3)%, respectively, with down-regulation of Pyk2 but not Paxillin.
      CONCLUSION: Pyk2 is involved in the regulation of cellular adherence function.
      Bortezomib might inhibit HL-60 cells adhension function by down-regulation of
      Pyk2 expression.

PMID- 19176040
TI  - [Diagnostic value of FDG-PET in the detection of bone marrow involvement in
      patients with diffuse large B-cell lymphoma].
AB  - OBJECTIVE: To evaluate the diagnostic value of bone marrow (BM) involvement
      detected by F-18-fluorodeoxyglucose-positron emission tomography/computed
      tomography ((18)F-FDG PET/CT) in patients with newly diagnosed diffuse large B
      cell lymphoma (DLBCL). METHODS: The study population comprised 81 consecutive
      patients with newly diagnosed DLBCL. All patients had both (18)F-FDG PET/CT and
      standard BM biopsy at iliac crest. In 9 patients, additional direct BM biopsy at
      FDG-avid bone lesion was performed. RESULTS: Among all 81 cases, 23 were
      diagnosed as BM involvement by PET/CT. Of the 23 positive cases 17 were confirmed
      by biopsy. However, only 11 cases were diagnosed by merely bilateral iliac crest
      biopsy. In patients in early stage of disease (18)F-FDG PET/CT had the same
      results as bilateral iliac crest biopsy. CONCLUSION: (18)F-FDG PET/CT is superior
      to standard BM biopsy in detecting BM involvement in newly diagnosed DLBCL
      patients. In patients with FDG-avid bone lesions, direct PET/CT-guided bone
      biopsy seems to be more accurate than standard BM biopsy.

PMID- 19176054
TI  - [Study on activation of AKT/mTOR pathway in anaplastic large cell lymphoma].
AB  - OBJECTIVE: To study the expression of anaplastic lymphoma kinase (ALK) and the
      phosphorylation status of AKT, mammalian target of rapamycin (mTOR), 4E-binding
      protein 1 (4E-BP1) and ribosomal protein S6 kinase (p70S6K) and their
      interrelationships and clinical pathological significance in anaplastic large
      cell lymphoma (ALCL) patients. METHODS: Immunohistochemical and EnVision methods
      were used to detect the expression of ALK, p-AKT, p-mTOR, p-4E-BP1 and p-p70S6K.
      RESULTS: Among the 81 ALCL patients, 51 (63.0%) expressed ALK, whereas the other
      30 (37.0%) did not. Patients with ALK(+) ALCL had a better prognosis than those
      with ALK-ALCL (P < 0.05). Out of the 71 ALCL samples studied, p-AKT was detected
      in 54 (76.1%) samples and its phosphorylation was correlated with ALK expression
      (P < 0.05); p-mTOR was detected in 57 (80.3%) samples and its expression was
      correlated with both ALK and p-AKT (P < 0.05); p-4E-BP1 and p-p70S6K were
      detected in 64 (90.1%) and 66 (93.0%) samples respectively, and their expressions
      were related with p-mTOR (P < 0.05), but not with ALK or p-AKT (P > 0.05). COX
      Proportional Hazard Model analysis showed that both the expression of ALK and the
      B symptoms affected the prognosis (P < 0.05), moreover, the former had greater
      impact than the later. CONCLUSION: Expressions of p-AKT, p-mTOR, p-4E-BP1 and p
      p70S6K are detected in ALCL, while ALK(+) cases have higher incidence than those
      with ALK(-) cases. Phosphorylation of AKT and mTOR is correlated with ALK
      expression, suggesting that there is an activated pathway of AKT/mTOR in patients
      with ALK(+) ALCL, but the activation have no obvious prognostic significance.

PMID- 19176055
TI  - [Effect of cytochrome CYP2C19 on the anti-myeloma activity of thalidomide in
      vitro].
AB  - OBJECTIVE: To investigate the effect of human liver microsome on anti-myeloma
      activity of thalidomide (TH) in vitro and identify the role of cytochrome CYP2C19
      in it. METHODS: Human multiple myeloma (MM) cell lines U266, NCI-H929, RPMI 8226,
      LP-1 and CZ-1 were treated with TH or TH pre-incubated with human liver
      microsome. Cell viability was detected by MTT assay, and cell cycle and apoptosis
      by flow cytometry (FCM). RESULTS: TH treatment had no direct effect on cell
      viability at concentrations of 10 microg/ml, 50 microg/ml and 100 microg/ml, the
      viabilities of the 5 MM cell lines were 96.2% - 103.7%, 96.3% - 103.7% and 97.9% 
      106.5% respectively, being no significant difference from that of control (P >
      0.05). However, when preincubated with human liver microsome, TH significantly
      inhibited the cell viability with a dose-dependent manner. At concentrations of
      10 microg/ml, 50 microg/ml and 100 microg/ml, TH pre-incubated with human liver
      microsome led to 12.2% - 22.9%, 25.9% - 36.4% and 34.9% - 46.3% decreases of cell
      viability, respectively (P < 0.05). TH at concentration of 100 microg/ml pre
      incubated with human liver microsome caused an increase of 18.5% - 32.5% in
      apoptosis cells. When omeprazole, a specific inhibitor of cytochrome CYP2C19, was
      added in the incubation system, the inhibition of cell viability by TH was
      weakened. At concentrations of 5 micromol/L and 10 micromol/L, omeprazole
      reversed the cell viability by 7.5% - 21.9% and 19.1% - 38.3%, respectively (P <
      0.05). CONCLUSION: Treatment of TH with human liver microsome is essential for
      its anti-myeloma activity in vitro, and cytochrome CYP2C19 is involved with this
      metabolism process.

PMID- 19176056
TI  - [Role of multiple myeloma cells on normal endothelial cells in co-culture
      system].
AB  - OBJECTIVE: To study the influence of multiple myeloma (MM) cells on normal
      endothelial cells in co-culture system in vitro. METHODS: A co-culture system of
      human MM cell line RPMI8226 with human umbilical vein endothelial cells (HUVECs)
      was established in vitro. Mono-cultured normal endothelial cells were used as
      control. Light microscopy and transmission electron microscopy were used to
      observe the morphology of the endothelial cells. The effects of HUVECs co
      cultured with RPMI8226 on HUVECs angiogenesis were studied by modified transwell
      migration assay and net-like formation assay. The protein expression of brain
      derived neurotrophic factor (BDNF), TrkB, Endoglin, Tie-2, beta 3 integrin and
      vascular cell adhesion molecule-1 (VCAM-1) in HUVECs were determined by FACS and
      Western blot analysis, respectively. RESULTS: The morphology of HUVECs co
      cultured with RPMI8226 cells became a narrower apart of extended shape as they
      began to align themselves. The sizes of nucleus and nucleolus were enlarged with
      an increased ratio of nuclear to nucleoplasm. The endoplasm was lose and
      distorted and the number of surface microvilli decreased. The RPMI8226 cell
      stimulated the migration and net-like formation of HUVEC, the number of net-like
      structure and migration cell being increased by 112% and 136%, respectively,
      compared with that of mono-cultured HUVECs. The expressions of BDNF, TrkB,
      Endoglin, Tie-2, beta 3 integrin and VCAM-1 in the ECs co-cultured with RPMI8226
      were all up-regulated in comparison with those in the controls. CONCLUSION: The
      MM cells promote formation of new vessels in co-cultured endothelial cells and
      the endothelial cells in MM are different from the normal ECs in character, and
      behavior.

PMID- 19176057
TI  - [Blockage of mTOR signaling pathway by rapamycin contributes to inhibition of
      tumor cell proliferation in ALK-positive lymphoid cell strains].
AB  - OBJECTIVE: To investigate the relationship between mTOR signaling pathway and ALK
      positive lymphoid cell lines. METHODS: The expression of the downstream effector
      proteins of mTOR were analyzed by Western blot before and after Karpas299,
      BaF3/NPM-ALK and BaF3 cell lines treated with rapamycin. Effect of rapamycin on
      cell proliferation was detected by MTT assay. FACS was used to analyze apoptosis
      and cell cycles. RESULTS: mTOR signaling phosphoproteins, p-p70S6K and p-4E-BP1
      were highly expressed in ALK(+) Karpas299, BaF3/NPM-ALK and parental BaF3 cell
      lines, and they were dephosphorylated after 1 h withdrawal of IL-3 in BaF3 cells.
      After 48 h exposure to 10 nmol/L rapamycin, p-p70S6K and p-4E-BP1 proteins
      expression were decreased, and mainly for the former. The relative inhibitory
      rate to its control cells was 24.4% in Karpas299, 37.8% in BaF3/NPM-ALK and 61.6%
      in BaF3. The apoptotic ratio was increased from (11.97 +/- 0.11)% to (15.87 +/-
      0.62)% in Karpas299 (P < 0.05), from (3.23 +/- 0.11)% to (7.67 +/- 0.49)% in BaF3
      (P < 0.05) and from (1.90 +/- 0.47)% to (2.80 +/- 0.27)% in BaF3/NPM-ALK (P >
      0.05). The fraction of G(1) phase cells increased from (37.63 +/- 1.91)% to
      (69.77 +/- 5.44)% in BaF3/NPM-ALK, from (31.13 +/- 2.51)% to (40.70 +/- 1.47)% in
      Karpas299 and (53.57 +/- 2.22)% to (63.70 +/- 1.20)% in BaF3 (P < 0.05).
      CONCLUSION: NPM-ALK kinase can activate mTOR signaling pathway. Rapamycin can
      inhibit the proliferation of ALK(+) lymphoid cells by blocking mTOR signaling
      pathway and inducing cell cycling arrest at G(1) phase.

PMID- 19176059
TI  - [Clinical significance of dynamic monitoring of cell chimerism following
      allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To evaluate the relationship of chimerism status of cell subsets with
      engraftment, occurrence of acute graft versus host disease (aGVHD), graft
      rejection and disease relapse after allogeneic hematopoietic stem cell
      transplantation (allo-HSCT). METHODS: Chimerism status in peripheral blood (PB)
      and bone marrow (BM) of 65 patients received allo-HSCT were monitored at regular
      intervals post-transplant. Fluorescence-activated cell sorter (FACS) was used to
      sort CD3(+)T lymphocytes in 65 cases, CD3(-)CD56(+)CD16(+)NK cells in 52 cases,
      CD15(+) granulocytes in 32 cases and CD19(+)B lymphocytes in 20 cases post
      transplants. The chimerism status of different lineage cells was analyzed by
      polymerase chain reaction amplification of short tandem repeats (PCR-STR).
      RESULTS: On day +7, NK-cells donor chimerism (DC 55.5%) was higher than other
      cell subsets. T lymphocyte was the latest one to reach complete donor chimerism
      (CDC) with a median on day +21. Patients whose T lymphocytes donor chimerism was
      more than 70% on day +7 and more than 95% on day +14 had a high risk for acute
      aGVHD. In all cases except those with ALL, the decreased DC of T lymphocytes were
      observed before molecular or hematological relapse occurred. CONCLUSION: Serial
      and quantitative T cell chimerism analysis provides a reliable and rapid
      screening method for the early detection of engraftment, graft rejection, disease
      relapse and occurrence of aGVHD, therefore, is a prognostic tool to identify
      patients at high risk of aGVHD and disease relapse following allo-HSCT.

PMID- 19176062
TI  - [Detection of clonal immunoglobulin and T-cell receptor gene rearrangements in
      newly diagnosed adult patients with acute lymphoblastic leukemia by using
      multiplex PCR protocols].
AB  - OBJECTIVE: To provide the evidence of RQ-PCR-based assessment of minimal residual
      disease (MRD), the clonal immunoglobulin and T-cell receptor (Ig/TCR) gene
      rearrangements were identified in newly diagnosed adult patients with acute
      lymphoblastic leukemia (ALL) by multiplex PCR protocols. METHODS: Forty newly
      diagnosed adult patients with B-lineage (B-) and T cell (T-) ALL were involved in
      this study. All DNA samples were obtained from the bone marrow (BM) mononuclear
      cells (MNC). IgH, IgK, TCRB, TCRG and TCRD gene rearrangements were detected by
      BIOMED-2 multiplex PCR protocols, which included 96 different primers and 14
      multiplex PCR tubes. RESULTS: The clonal immunoglobulin (Ig) rearrangements were
      found in 96% of B-ALL, 86% being IgH and 14% IgK. While in T-ALL, clonal TCR
      rearrangements were found in all of the patients, 83% being TCRB, 78% TCRG and
      39% TCRD. More than two clonal markers were found in 91% of B-ALL and 89% of T
      ALL patients. CONCLUSIONS: The detection rate of clonal rearrangements using the
      BIOMED-2 14 multiplex PCR tubes is high, which can detect virtually all clonal B
      and T-cell proliferations. It can be used for diagnostic clonality studies as
      well as for the identification of PCR targets suitable for the detection of
      minimal residual disease.

PMID- 19176061
TI  - [Monitoring AML1-ETO mRNA levels by real-time quantitative RT-PCR in t(8;21)
      acute myeloid leukemia patients after hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To evaluate the value of real time quantitative RT-PCR (Q-PCR) for
      monitoring AML1-ETO mRNA levels in AML1-ETO(+) acute myeloid leukemia (AML)
      patients following allogeneic hematopoietic stem cell transplantation (allo
      HSCT). METHODS: Quantification of AML1-ETO(+) mRNA was performed serially on bone
      marrow samples from 17 patients with AML1-ETO(+) AML after HSCT. Q-PCR used the
      TagMan probe system. The AML1-ETO mRNA level was normalized by control gene abl.
      Cytogenetic response was evaluated by fluorescent in situ hybridization (FISH).
      RESULTS: The reproducible sensitivity of Q-PCR was 5 copies. Out of 16 patients
      who achieved sustained complete cytogenetic response (CCyR), one each died of
      graft-versus-host disease and infection. The median AML1-ETO mRNA levels in the
      rest of 14 CCyR patients were 0 (0 - 0.740), 0.026 (0 - 2.900), 0.039 (0 - 3.300)
      at +1, +2, +3 month post allo-HSCT, respectively and in 5 CCyR patients beyond 1
      year following allo-HSCT (median follow-up 685 days) was 0.078 (0.003 - 0.120).
      The AML1-ETO mRNA levels in one relapsed patient were 0, 9.8 and 5.6 at +1, +2
      and +3 month post allo-HSCT, respectively and hematological relapse occurred at
      +110 day, when the AML1-ETO mRNA levels increased dramatically from 5.600 to
      390.000. CONCLUSIONS: Q-PCR is a sensitive technique in monitoring AML1-ETO(+)
      AML patients post allo-HSCT. Persistence of a low level within one year after
      allo-HSCT does not mean at risk of relapse. It is necessary to dynamic monitoring
      AML1-ETO mRNA after remission in t(8;21) AML patients.

PMID- 19176063
TI  - [Study on differentiation of mesenchymal stem cells derived from human umbilical
      cord blood into insulin secreting cells].
AB  - OBJECTIVE: To investigate the differential potential of mesenchymal stem cells
      (MSCs) derived from human umbilical cord blood (hUCB) into insulin-secreting
      cells and its inducing condition. METHODS: UCB nucleated cells (NCs) were
      isolated and cultured in Mesencult media. The obtained UCB MSC were purified by
      adherence method and expanded. Then they were induced with epidermal growth
      factor (EGF), B-mercaptoethanol and high concentration of glucose. The induced
      cells were identified by RT-PCR. Intracellular insulin was examined by
      immunocytochemistry. The quantity of insulin secretion and glucose-simulated
      insulin release were examined by chemiluminescence immunoassay. The induced cells
      were also transplanted into renal subcapsular space of STZ-induced hyperglycemic
      mice to observe the in vivo lowering effect on hyperglycemia. RESULTS: The
      induced cells morphologically became round and were gathering into a mass. The
      expression of some genes related to pancreatic islet was found by RT-PCR.
      Chemiluminescence immunoassay showed insulin positivity and the cells secreted a
      low concentration of insulin [(0.37 +/- 0.06) mU/L]. The induced cells responded
      to high glucose challenge with a stimulation index of 1.76. After those cells
      grafted into renal sub-capsule there was an in vivo lowering effect on blood
      glucose level on STZ hyperglycemic mice. CONCLUSION: MSCs from UCB can
      differentiated into insulin secreting cells.

PMID- 19176087
TI  - [Pay attention on the normalization of diagnosis and treatment for amblyopia].
AB  - We need to establish a guidelines for the prevention and treatment of children
      amblyopia. In this amblyopia treatment system, high quality optic correction
      should be emphasized, customized occlusion therapy should be made based on the
      type of amblyopia, and the age of the patient. Penalization therapy is highly
      suggested to moderate and mild amblyopia, as well as patients with poor
      compliance. Multiple-center research with random comparison is expected, which
      will evaluate the effect of current treatment with the methods of evidence based
      medicine.

PMID- 19176064
TI  - [Study on hematopoiesis reconstitution by co-transplant of human bone marrow
      mesenchymal stem cells and umbilical cord blood CD34(+) cells at different ratios
      in NOD/SCID mice].
AB  - OBJECTIVE: To study the effect of co-transplant of human bone marrow mesenchymal
      stem cells (BMMSCs) and umbilical cord blood (UCB) CD34(+) cells on hematopoiesis
      reconstruction in NOD/SCID mice and to investigate the optimal proportion between
      the two kind of cells. METHODS: Female NOD/SCID mice were sublethally irradiated
      by (60)Co gamma-ray and transplanted with BMMSCs and different ratios of UCB
      CD34(+) cells. From day +3 till day +42 after transplantation, 20 microl
      peripheral blood (PB) was collected from the retro-orbital plexus of mice weekly,
      and the variations of WBC and PLT were counted. Mice were sacrificed 42 days
      after transplantation, and human CD45 positive (huCD45(+)) cells in PB, BM, and
      spleen were detected by flow cytometry. RESULTS: Compared with transplant of UCB
      CD34(+) cells alone, co-transplantation of BMMSCs and UCB CD34(+)cells at ratios
      of 1:1, 5:1 and 10:1, (1) significantly mitigated the decrease range (P < 0.01)
      and led to the recovery of WBC and platelet in PB one week earlier (P < 0.05),
      and the difference among the three groups was not statistically significant (P >
      0.05); (2) significantly enhanced hematopoietic stem cells (PB, BM and spleen
      cells) engraftment in recipient mice, and the effect was most pronounced at the
      ratio of 10:1. huCD45(+) cells in PB, BM and spleen were increased by (2.75 +/-
      0.63), (3.51 +/- 0.86) and (5.18 +/- 0.57) fold, respectively (P < 0.01).
      CONCLUSION: The optimal hematopoiesis reconstruction is achieved by co-transplant
      of UCB CD34(+) cells and BMMSCs at a ratio of 1:10.

PMID- 19176088
TI  - [The esotropia of the convergence-excess type subdivided into two forms].
AB  - There are two types of convergence excess esotropia in the classification of
      strabismus in our country. One is nonrefractive accommodative esotropia and
      another is nonaccommodative convergence excess esotropia. Inadequate heterophoria
      method to determine the AC/A ratio does not distinguish between a high AC/A ratio
      and nonaccommodative convergence excess. The diagnosis of nonrefractive
      accommodative esotropia is based on the presence of a high AC/A ratio as
      established with the gradient method to distinguish this condition from
      nonaccommative convergence excess.

PMID- 19176089
TI  - [Observation of botulinum toxin A management in childhood with intermittent
      exotropia].
AB  - OBJECTIVE: To observe the effect of botulinum toxin A (BTXA) management in
      childhood with intermittent exotropia. METHODS: A prospective non-random clinical
      study was performed in 60 children aged from 4 to 12 years, who diagnosed to be
      intermittent exotropia. Patients were divided into surgery groups and BTXA group
      according to the intention of patient's parent. The recession of bilateral rectus
      muscle was performed in 30 patients in surgery group. BTXA injection into
      bilateral rectus muscle was performed in 30 patients in BTXA group. Eye alignment
      and the binocular vision were evaluated 6 months after the treatments. RESULTS:
      In BTXA group, the deviation was (-41.33 +/- 12.17)Delta (-30Delta to -75Delta)
      at the baseline, and (6.23 +/- 9.80)Delta (-30Delta to 0Delta) 6 month after BTXA
      injection. Among the patients, 7 cases were under-correct. In surgery group, the
      deviation was (-42.83 +/- 11.72)Delta (-25Delta to -80Delta) at the baseline, and
      (2.67 +/- 5.21)Delta (-15Delta to +15Delta) 6 months after surgery. Among these
      patients, 1 case was under-corrected, and 2 cases were overcorrected. The
      recovery rate was 76.67% and 90.00% respectively in BTXA and surgery group, and
      was no statistically significant difference these two groups (P = 0.177) and the
      recovery rate (chi2 = 0.42, P = 0.166). Some patients were found to have fusion
      and distance stereopsis re-built, while some others were found to have near
      stereopsis improvement in both groups. CONCLUSION: BTXA injection is a rapid,
      less invasive and effective procedure for the intermittent exotropia.

PMID- 19176090
TI  - [The surgical management of strabismus following orbitotomy].
AB  - OBJECTIVE: To analyze the clinical features and therapeutic outcome in patients
      with strabismus due to orbitotomy. METHODS: Retrospective case series. Nine cases
      of strabismus following orbital operation seen between March 1998 and July 2003
      in Zhongshan Ophthalmic Center, Sun Yat-sen University were reviewed
      retrospectively. RESULTS: All of the 9 cases were treated by strabismus surgery.
      Among them, 5 cases were male and 4 were female, with their age ranging from 12
      to 40 years (average 26.4 years). The right eye was involved in 4 cases and the
      left one in 5 cases. Most of them belonged to restrictive strabismus secondary to
      the formation of surgical scar, accounting for 66.7% of them. The methods of
      surgery included the excision of fibrous tissue around the involved extraocular
      muscle, the routine recession and resection and the Jensen procedure, combined
      with the fixation suture. Six cases obtained excellent results. Two cases were
      slightly undercorrected and one case was remarkably undercorrected. Of the 4
      cases with diplopia before operation, the diplopia disappeared in 2 cases after
      surgery. The other 2 cases had diplopia only in one direction far away from the
      primary position. All of the ocular movement improved obviously after strabismus
      surgery. CONCLUSIONS: Most of the deviation happened after orbitotomy was
      restrictive strabismus caused by the muscle fibrosis and scar formation around
      the muscle. Excision of fibrotic tissue, combined with the routine recession and
      resection, Jensen procedure, and the fixation suture can have quite satisfactory
      results.

PMID- 19176091
TI  - [The changes of AMPA receptors subunit GluR2 and mEPSCs in visual cortex of
      monocular deprivation rats].
AB  - OBJECTIVE: To observe the change of expression in quantity of AMPA receptor
      subunit GluR2 and mEPSCs from monocular derivated rats. The preparative work was
      conducted for the further study on mechanism involved in regulation and control
      of the visual development plasticity. METHODS: It was an experimental study.
      Forty 14 d healthy Wistar rats were divided into two groups randomly; twenty in
      each group which were divided into two groups (I, II) and derivated monocular in
      experiment group (group I), and then were killed at a week later. ForIA and IIA 5
      microm thick section was cut from tissue of visual cortex in coronary side, then
      the expression of GluR2 was observed by microscope and image analyze of GluR2 was
      conducted after immunohistochemical staining; for IB and IIB, mEPSCs was
      investigated which was used Voltage-clamp technique with whole-cell mode. RESULT:
      The level of GluR2 in visual cortex of normal rats was higher than experiment
      group. The mean amplitude and frequency of mEPSCs increased in the derivated
      monocular group. CONCLUSIONS: The level of GluR2 has changed association with the
      visual stimulation, which suggests that GluR2 should have the important
      physiological function on the postnatal development of visual system of rats.

PMID- 19176092
TI  - [Preliminary outcome of large-diameter lamellar keratoplasty combined with deep
      lamellar endothelial keratoplasty for whole cornea destruction].
AB  - OBJECTIVE: To understand the indication, surgical principle, outcome and
      complications of large-diameter lamellar keratoplasty combined with deep lamellar
      endothelial keratoplasty for whole cornea destruction. METHODS: Eleven
      hospitalized patients with whole cornea destruction in Zhongshan Ophthalmic
      Center, Sun Yat-Sen University from May, 2005 to March, 2006 were involved in
      this study. Five left eyes and six right eyes underwent large-diameter lamellar
      keratoplasty combined with deep lamellar endothelial keratoplasty. The patients
      were followed up for 12 to 18 months and their pinhole postoperative visual
      acuity, intraocular pressure, pachymetry of the central cornea and corneal
      endothelial cell density was recorded. RESULTS: The pinhole postoperative visual
      acuity of all patients improved and averaged separately 4.4 +/- 0.3, 4.5 +/- 0.3
      and 4.5 +/- 0.3 at the 3rd, 6th and 12th postoperative month. There was a
      temporary increase of the postoperative intraocular pressure within one
      postoperative week which can be controlled by medication and released soon. And
      the postoperative intraocular pressure averaged (19.8 +/- 2.7), (19.2 +/- 1.7)
      and (19.5 +/- 2.0) mm Hg respectively at the 3rd, 6th and 12th month
      postoperatively. At the same following up times, the pachymetry of the central
      cornea averaged (538.9 +/- 8.9), (536.3 +/- 6.3) and (537.2 +/- 6.9) microm
      respectively and the corneal endothelial cell density averaged (2519.8 +/-
      110.7), (2244.4 +/- 137.9) and (2093.3 +/- 141.9) cells/mm2 respectively. The
      main complication was the interspace between the two lamellar grafts and it would
      disappear automatically within one postoperative month. CONCLUSIONS: Large
      diameter lamellar keratoplasty combined with deep lamellar endothelial
      keratoplasty can avoid postoperative glaucoma. It may offer further advantages
      over traditional surgery to treat whole cornea destruction.

PMID- 19176093
TI  - [Morphological changes of cornea in iridocorneal endothelial syndrome under the
      confocal microscopy].
AB  - OBJECTIVE: To evaluate the morphological changes of cornea in iridocorneal
      endothelial syndrome (ICE) under the examination of in vivo confocal microscopy.
      METHODS: The experimental design was retrospective observation case series.
      Twenty-three eyes of 23 consecutive patients, each diagnosed as ICE, had their
      both eyes examined with the in vivo confocal microscopy (NIDEK, confoscan 3.0).
      The images were recorded and analyzed by software NAVIS. Measurements were
      performed on endothelium density, average endothelial area, the percentage of
      hexagonal cells and the percentage of endothelium with nuclei, and the ANOVA was
      done to assess the differences. RESULTS: In vivo confocal microscopy highlighted
      two main patterns of endothelial changes: "kite-like" and "epithelial-like"
      abnormal endothelium, characterised by marked hyperreflective nuclei and loss of
      regularity in cellular size and shape. With the progression of disease, the
      endothelium density and the percentage of hexagonal endothelial cells decreased,
      which were (1687.1 +/- 122.6), (1210.6 +/- 168.7), (947.3 +/- 145.2), (856.8 +/-
      73.4) cells/mm2 and (51.5 +/- 6.3)%, (39.8 +/- 9.2)%, (32.7 +/- 8.1)%, (24.1 +/-
      5.6)% respectively in detail. In contrast, the average endothelial area the
      percentage of endothelium with nuclei increased, which were (678.3 +/- 56.3),
      (928.7 +/- 96.2), (1188.5 +/- 72.6), (1337.5 +/- 60.8) microm2 and (12.6 +/-
      1.4)%, (56.8 +/- 3.7)%, (78.7 +/- 5.6)%, (84.3 +/- 2.8)%. The differences all had
      statistical significance (F = 7.158, 7.736, 6.876, 14.452 respectively, P =
      0.000). The morphology of keratocyte and endothelium were normal, compared with
      the contralateral healthy eyes. However, the stromal nerves became thicker and
      more tortuous with the disease advancement. CONCLUSIONS: The application of
      confocal microscopy indicates that the ICE is characterised by epithelial-like
      endothelial cells with hyperreflective nuclei. The technique has great potential
      in diagnosing ICE, especially in evaluating the disease progression.

PMID- 19176094
TI  - [Primary iris-ciliary body cyst and its relevancy with the change of anterior
      chamber angle].
AB  - OBJECTIVE: To investigate the characteristics of the size and distribution of
      primary iris-ciliary body cysts and its associated with the change of anterior
      chamber angle. METHODS: It was a cross sectional study. Patients with shallow
      anterior chambers found in routine health examinations were evaluated with UBM
      scan. Any primary iris-ciliary body cysts detected were recorded in the
      parameters of quantity, size, location, and quadrant. The shape of the angle in
      the UBM was compared to the surrounding area of angle without the cyst, and also
      whether the angle was narrowed or closed was recorded. The factors related to the
      corresponding narrowed or closed angle were analyzed. RESULTS: The 502 cysts were
      detected in 134 (29.32%) of the 457 patients, which were all primary iris-ciliary
      body cysts. The cysts were located in the iridociliary sulcus (41.24%) and pars
      plicata (58.37%) and distributions were 44.22% situated at the inferotemporal
      quadrant, 26.88% at the inferonasal quadrant, 23.11% at the superotemporal
      quadrant and 5.38% at the superonasal quadrant. The largest base size of the
      cysts was 0.6289 +/- 0.2329 mm and most were mid-sized cysts (86.05%). The
      incidence of the cysts with corresponding chamber angle narrowing or closure in
      the iridociliary sulcus was 82.13% (170/207), and in the pars plicata was 22.87%
      (67/293). The difference between them was statistical significant (chi2 = 170.83,
      P < 0.01). The relationship between the cyst size and the proportion of the cysts
      which caused corresponding angles narrowing or closure was analyzed by way of
      rectilinear correlation, and it was found to be a positive correlation (r =
      0.9939, P < 0.01). CONCLUSIONS: The incidence of primary iris-ciliary body cysts
      in the normal population is high and some may cause corresponding angle narrowing
      or closure; The location and size of the cysts are the factors to induce
      narrowing or closure of the angle in the corresponding area.

PMID- 19176095
TI  - [Clinical features of silicone oil dependent eyes].
AB  - OBJECTIVE: To study the clinical features of silicone oil dependent eyes. METHOD:
      Retrospective observational case series. Twenty four silicone oil dependent eyes
      collected from the Peking Union Medical College from Jan.2000 to Dec.2006 were
      studied. The pathogeny, surgical process and prognosis were analyzed. RESULTS:
      There were 5.9% silicone oil dependent eyes in eyes underwent vitrectomy and
      silicone oil tamponade. Silicone oil tamponade was performed again in 17 eyes
      because of severe proliferative vitreoretinopathy (PVR) or repeated vitreous
      hemorrhage after silicone oil removal and C3F8 tamponade. Silicone oil
      replacement was performed in 3 eyes because of severe PVR. Continually low
      intraocular pressure occurred after silicone oil removal in 4 eyes with 360
      degree peripheral retinotomy. Thirteen of 24 patients had visual acuities of
      finger counting to 0.1, 9 had hand movement, one had light perception and one had
      no light perception. CONCLUSIONS: The incidence of silicone oil dependent eye is
      approximately 5.9%. This is often seen in the patients with severe or repeated
      PVR, or 360 degree peripheral retinotomy. The visual prognosis is poor in most
      cases.

PMID- 19176096
TI  - [Prophylactic laser treatment to macular soft drusen in age-related maculopathy
      of updated results].
AB  - OBJECTIVE: To investigate the follow-up results of the prophylactic laser
      treatment to macular soft drusen in age-related macular degeneration. METHODS:
      Prospective, 10 persons with bilateral soft drusen and with good visual acuity
      were observed for 8 years. 10 eyes were treated. The fellow eyes were as control
      group. Fluorescein angiography and Amsler test were studied after 8 years.
      Scanning laser ophthalmoscope was performed after 2 years. Some of them were
      performed multifocal ERG to test the macular function after 3 years. RESULTS:
      There is no choroidal neovascularization in both the laser group and the control
      group. There is no differences in the best corrected visual acuity after 8 years.
      All eyes had good fovea fixation. Light sensitivity of both eyes had no
      significant difference to be found by scanning laser ophthalmoscope. The
      latencies and amplitude densities of the N1 and P1 waves in the central first
      ring remained unchanged at 3 years post-treatment (before treatment t = -0.779,
      0.722, -0.491, 0.286; after treatment t = 1.342, 0.043, 0.937, 0.350; P > 0.05)
      compared with the fellow eyes. CONCLUSIONS: There is no impairment to be found in
      the macula after preventive laser treatment. The treatment did not demonstrate a
      clinically significant benefit for choroidal neovascularization in eyes of people
      with bilateral large drusen.

PMID- 19176097
TI  - [Exploration of three-dimensional biometric measurement of emmetropic adult eye
      ball by using magnetic resonance imaging technology].
AB  - OBJECTIVE: To study biometric measurements of emmetropic adult eyes with magnetic
      resonance imaging technology (MRI). METHOD: MRI technology, with super
      resolution, hyper-speed imaging and the integration of the thin-scanning layer,
      is applied to measure the three-dimensional biometric parameters of the eyeball.
      From January to December, 2003, emmetropic eyes from 31 normal Chinese adults (16
      males and 15 females) aged from 18 to 32 years old (23.32 +/- 3.32) were
      successfully measured to obtain the volume of the eyeball and vitreous cavity;
      inner dimensions of the eye, including the anterior-posterior, vertical and
      horizontal diameters. The length of ocular axis was measured by A-echo too. Data
      was analyzed by SPSS 11.0 statistical software. RESULTS: The volume of the
      eyeball, anterior chamber, lens and the vitreous cavity is (6.013 +/- 0.449) ml,
      (0.348 +/- 0.020) ml, (0.183 +/- 0.015) ml, and (5.482 +/- 0.440) ml,
      respectively. The length of anterior-posterior diameter of the vitreous cavity is
      (16.008 +/- 0.707) mm. The ocular inner dimensions of horizontal, vertical and
      anterior-posterior planes were (22.455 +/- 0.983) mm, (23.290 +/- 0.815) mm and
      (22.619 +/- 0.912) mm, respectively. The length of the ocular axis is (23.10 +/-
      0.92) mm (with MRI & Orbscan II) and (23.67 +/- 0.82) mm (with A-echo).
      CONCLUSIONS: The value of the ocular length in emmetropic eye measured with both
      MRI + Orbscan II and the (A-echo) in the present study is very close to the value
      of the Bennett-Rabbitts schematic eye (24.09 mm). MRI technology is valuable for
      obtaining more reliable and precise data in the study of ocular physiology and
      clinical ophthalmology.

PMID- 19176098
TI  - [Effects of extract of Buddleja officinalis on prevention of dry eye in castrated
      rabbits].
AB  - OBJECTIVE: To assess the preventive effects of extract of Buddleja officinalis on
      dry eye in castrated rabbits and to discuss the mechanism of these effects.
      METHODS: It was a experimental study. Thirty male rabbits were divided equally
      into normal group (A), disease group (B) and treatment group (C, D, and E). The
      dry eye model was established with orchiectomy (ORX) in Group B, C, D and E.
      Group C, D and E were gastrically perfused with single-dose or double-does of
      Buddleja officinalis extract or genistein for 30 days. All rabbits were examined
      with Schirmer I test (SIT). TGF-beta1, IL-1beta, TNF-alpha, Fas, FasL, Bax and
      bcl-2 were detected by immunohistochemistry. Morphological and ultrastructure
      changes were observed by electron microscopy. RESULTS: The SIT value of group C,
      D, E was significantly greater than that of group B (P < 0.01). The expression of
      IL-1beta, TNF-alpha, Fas, FasL and Bax in acinar cells and glandular tube cells
      of group C, D, E were significantly lower than those of group B (P < 0.01) and
      the expression of TGF-beta1 and bcl-2 in acinar cells and glandular tube cells of
      group C, D, E were significantly higher than those of group B (P < 0.01).
      Furthermore, ultrastructure of lacrimal gland in group C, D, E was much healthier
      than that of group B. The results obtained from all of these studies showed that
      the lacrimal glands status in group C, D was significantly better than that of
      group E (P < 0.05). CONCLUSION: Extract of Buddleja officinalis has a significant
      effect on the prevention of experimental dry eye in castrated male rabbits. The
      main components of extract of Buddleja officinalis are the flavonoids. The
      flavonoids display androgen-like activity. Therefore, it can adjust gonadal
      hormone level in vivo. As a result, it can inhibit local inflammation in lacrimal
      gland and reduce apoptosis of lacrimal gland cells.

PMID- 19176099
TI  - [Ultrastructure study of pathogen of acanthamoeba keratitis].
AB  - OBJECTIVE: To observe the ultrastructure of the strains of acanthamoeba isolated
      from acanthamoeba keratitis (AK), the morphologic changes of acanthamoeba after
      culture with 0.02% chlorhexidine, and ultrastructure characteristics of
      acanthamoeba in corneal tissue of AK. METHODS: It was a experimental study. The
      ultrastructure of acanthamoeba strains cultured with 0.02% chlorhexidine was
      observed with scanning electron microscope (SEM). The excited cornea tissues from
      AK were observed with transmission electron microscope (TEM). RESULTS: Cultured
      acanthamoeba trophozoites were approximately 15 - 45 microm in diameter, appeared
      irregularly round or oval in shape, with rough surface and intrusion of
      cytoplasm. The trophozoite propagated by ways of binary division. The
      acanthamoeba cysts were approximately 10 - 25 microm in diameter, round in shape
      and with a plica-like surface. The acanthamoeba could change from trophozoite to
      cyst. The amoeba emerging through ostioles could turn into trophozoite and left
      an empty cyst. After cultured with 0.02% chlorhexidine for 24 hours, the
      trophozoite and cyst collapsed and distorted. However, after clinical treatment
      with 0.02% chlorhexidine, only the cysts could be seen in corneal tissue of AK.
      Ecto-and endo-cystic walls were preserved, but the cytoplasma was aggregated and
      the sub-cytoarchitecture were degenerated or disappeared. DISCUSSION
      Chlorhexidine at a concentration of 0.02% kills acanthamoeba trophozoites and
      cysts in vitro. Chlorhexidine (0.02%) also kills trophozoites and inhibits the
      activity of cysts in corneal tissues. However, it should be noticed that the
      inactive cysts can stay in the cornea for a long time and may cause an immuno
      pathologic inflammation of the cornea.

PMID- 19176107
TI  - [Synapse remodelling from functional to structural: neural mechanisms underlying
      amblyopia].
AB  - Visual experience plays an instructive role in the development of the visual
      nervous system., it can induce persistent modification of developing visual
      circuits via Hebb's synaptic plasticity. The application of in vivo two-photon
      imaging to monitor structural changes during Monocular deprivation (MD) will
      determine how amblyopia are related to remodelling of synapses. As the most
      important process of amblyopia, ocular dominance (OD) shifts served as a usefull
      model for examining how cortical circuits are shaped by experience. MD can induce
      OD shifts toward the no-visual deprivation eye, what are the neuronal mechanisms
      underlying it? How the functional plasticity turn to structural plasticity? Do
      the adults share the common mechanisms with the juveniles? In this review we will
      discuss the researching progress of neuronal mechanisms of amblyopia in these
      years.

PMID- 19176108
TI  - [Preclinical study update of bone marrow mesenchymal stem cells in treating eye
      diseases].
AB  - Bone marrow mesenchymal stem cell (BMSC) is a special kind of cells which has the
      ability of self-renewal, high proliferation and multi-potentialities. Because of
      the characteristic of plasticity, it plays an important role in the reparation of
      various tissues and organs. Furthermore it is convenient to harvest which should
      make it more applicable in tissue engineering. Here the pre-clinical study
      advance of BMSC in treating eye diseases is reviewed.

PMID- 19176110
TI  - [Concern on the changes of clinical pattern and etiological factors in uveitis in
      China].
AB  - The present paper addresses the changes of clinical pattern and etiological
      factors in uveitis in China. Behcet's disease and Vogt-Koyanagi-Harada syndrome
      have been shown to be the two most common and the most severe sight-threatening
      uveitis entities in China. Uveitis or endophthalmitis caused by tuberculosis,
      syphilis, fungi and acquired immune deficiency syndrome has increased in
      frequency during recent years. Masquerade syndrome seen in intraocular-central
      nervous system lymphoma, retinoblastoma and metastases of cancers to the eye is
      not a rare disease.

PMID- 19176111
TI  - [To pay attention to syphilitic uveitis].
AB  - There has been a dramatic increase in the incidence of syphilis over the last
      five years in the world. Some of the syphilitic patients have ocular uveitis as
      the initial presentation of syphilis, which may be misdiagnosed and can lead to a
      delay of treatment. Multiple manifestations of ocular syphilis include
      interstitial keratitis; anterior, intermediate, posterior uveitis and optic
      neuropathies. Uveitis, which may involve unilateral or bilateral eyes, is the
      most common ocular manifestation of syphilis. The serologic tests for syphilis
      should be considered for unexplained uveitis patients. All patients diagnosed
      with ocular syphilis should be tested for co-infection with human
      immunodeficiency virus. The preferred treatment for ocular syphilis remains high
      dose intravenous penicillin G.

PMID- 19176112
TI  - [Single nucleotide polymorphisms of promoter of human leukocyte antigen-DQB1
      alleles in Chinese Han patients with Vogt-Koyanagi-Harada syndrome].
AB  - OBJECTIVE: To investigate the single nucleotide polymorphism of the promoter of
      HLA-DQB1(QBP) in Chinese Han patients with Vogt-Koyanagi-Harada syndrome.
      METHODS: Case-control design was applied. Eighty-eight Chinese Han patients with
      Vogt-Koyanagi-Harada syndrome and 88 non-Vogt-Koyanagi-Harada syndrome controls
      were admitted. DNA was extracted from the peripheral white blood cells of the
      subjects by the phenol-chloroform method. Polymerase chain reaction-single strand
      conformation polymorphism (PCR-SSCP) and clone-sequencing were applied to
      determine the sequences of the promoter of HLA-DQB1. Chromans and Bioedit
      software were used to analyze the sequences of the promoter of HLA-DQB1. Chi
      square test and Fisher exact test were applied to compare the frequencies of
      bands of QBPs and SNPs for the two groups. RESULTS: Sixteen band patterns of HLA
      QBP were shown by polyacrylamide gel electrophoresis (PAGE). The band frequencies
      of QBPb (corresponding gene sequence was QBP2.1 + 77C > A, chi2 = 26.01, Pc <
      0.001) and QBPl (corresponding gene sequence was QBP3.3, chi2 = 16.99, Pc <
      0.001) were significantly higher in patients with Vogt-Koyanagi-Harada syndrome
      than that in normal controls (Pc < 0.001). However, the frequencies of QBPg
      (corresponding gene sequence was QBP3.1, chi2 = 12.10, Pc < 0.05) and QBPn
      (corresponding gene sequence was QBP6.1 + 39G > A, chi2 = 14.64, Pc < 0.05) were
      significantly lower in patients with Vogt-Koyanagi-Harada syndrome than those of
      the controls. Twelve SNPs were found in all subjects. The frequency of C allele
      at position -189C/A in patients with Vogt-Koyanagi-Harada syndrome was
      significantly higher than that in controls (chi2 = 45.92, P = 0.000). However,
      the frequency of G allele at position -227G/A in patients with Vogt-Koyanagi
      Harada syndrome was significantly lower as compared with that in the normal
      controls (chi2 = 15.63, P = 0.000). CONCLUSIONS: C allele of -189C/A is a
      genetically susceptible factor of Vogt-Koyanagi-Harada syndrome and G allele of 
      227G/A is the protective factor of Vogt-Koyanagi-Harada syndrome.

PMID- 19176113
TI  - [Expression of suppressor of cytokine signaling in retina of experimental
      autoimmune uveoretinitis].
AB  - OBJECTIVE: To investigate the expression and significance of suppressor of
      cytokine signaling (SOCS) mRNA and protein in retina of rats with experimental
      autoimmune uveoretinitis (EAU). METHODS: Research was designed with randomized
      controlled trials. Eighty Lewis rats were immunized with interphotoreceptor
      retinoid-binding protein (IRBP) to induce EAU. They were stratified randomly into
      two groups: nontreatment group (40 rats) and treatment group (40 rats). The
      treatment group was administered cyclosporine A 20 mg.kg(-1).day(-1) after
      immunization for 28 days, and the nontreatment group received saline buffer in
      the same way, ten normal Lewis rats without immunization and treatment as normal
      control group. The rats in both groups were stratified randomly into four sub
      groups. Each sub-group had 10 rats and the rats were sacrificed at day 0, 7, 14,
      21, 28 after immunization. All eyes were evaluated by slit-lamp microscopy.
      Retinas of rats were subjected to analysis of SOCS mRNA and protein expression
      using quantitative RT-PCR and western blot, respectively. IL-4, IL-12 and IFN
      gamma in the serum were measured by ELISA. RESULTS: At day 14, the nontreatment
      group developed acute anterior uveitis and showed typical signs including aqueous
      flare, small or irregular pupil due to posterior synechiae and hypopyon, the
      score of inflammation was 1.5 +/- 0.5; but the treatment group did not suffer
      from severe anterior chamber inflammation, the score of inflammation was 0.5 +/-
      0.3. The highest level of IL-4, IL-12 and IFN-gamma production occurred at day 14
      (P < 0.05), followed by decline in the secretion of IL-12 and IFN-gamma secretion
      to the baseline at day 28, while the concentration of IL-4 did not decrease
      significantly in the nontreatment group (P > 0.05). IL-12 and IFN-gamma did not
      change significantly (P > 0.05) and IL-4 production reached the highest level at
      day 28 in the treatment group. Both SOCS1 and CIS mRNA increased to the highest
      level at day 14. Compared to normal controls, the copies of SOCS1 and CIS mRNA
      were 3.41 fold and 3.36 fold in the nontreatment group, and were only 1.44 fold
      and 1.73 fold in treatment group, respectively. Both SOCS3 and SOCS5 mRNA reached
      the highest level at day 28 after immunization in both groups. The copies of
      SOCS3 and SOCS5 mRNA were 1.95 fold and 3.16 fold in the nontreatment group, and
      were 1.59 fold and 3.58 fold in the treatment group, respectively. Marked
      increased expression of SOCS1 and CIS proteins in the nontreatment group as
      compared to normal controls was detected at 7, 14, 21 days; in the treatment
      group these proteins only increased significantly at day 14 (P < 0.05).
      Expression of SOCS3 and SOCS5 proteins in both groups were higher than those in
      normal controls (P > 0.05). CONCLUSIONS: Marked increased expression of SOCS1 of
      retina may involve in the development of a Th1 mediated immune response in EAU.
      CIS and SOCS3 of retina may play important roles in mitigating pathogenic effects
      of proinflammatory cytokines during different stages of EAU. Up-regulation of
      SOCS5 may have protective functions.

PMID- 19176114
TI  - [Observation on surgical results of complicated cataract in patients with
      uveitis].
AB  - OBJECTIVE: To evaluate the efficacy of surgical intervention of complicated
      cataract in patients with uveitis. METHODS: Fifty-one patients (69 eyes) with
      complicated cataract secondary to uveitis who had cataract surgery in Peking
      Union Medical College Hospital between January 2000 and August 2006 were
      retrospectively analyzed. Surgical procedures, visual outcome, postoperative
      recurrence of uveitis and complications were investigated. RESULTS:
      Phacoemulsification was performed on 64 eyes (92.8%), while extracapsular
      cataract extraction (ECCE) was performed on the remaining 5 eyes (7.2%).
      Posterior chamber intraocular lens (IOL) was implanted in 61 eyes (88.4%), while
      the remaining 8 eyes (11.6%) remained aphakic, 6 of those were in patients who
      were blind in the other eye. At the final follow-up, 38 eyes (55.0%) had a best
      corrected visual acuity of 0.5 or better, an improvement that was highly
      significant (Z = 8.26, P < 0.001). Postoperative recurrence of anterior uveitis
      occurred in 19 (27.5%) eyes, however, 18 of them were pseudophakic, among which 5
      eyes had 3 or more episodes of recurrence. Neodymium: YAG (Nd: YAG) laser
      posterior capsulotomy was performed in 24 (34.8%) eyes, however, 23 of them were
      pseudophakic, among which 7 eyes underwent at least two separate capsulotomies.
      CONCLUSIONS: Surgical intervention of complicated cataract in patients with
      uveitis is effective and safe. In comparison with the pseudophakia group, less
      postoperative complications are found in patients without IOL implantation.
      Accordingly, it seems feasible that cataract extraction without IOL implantation
      is the procedure of choice for treating uveitis patients who are blind in the
      other eye.

PMID- 19176115
TI  - [Lacrimal intubation with the Ritleng system in congenital nasolacrimal duct
      obstruction in children].
AB  - OBJECTIVE: To evaluate the efficacy and complication of the Ritleng lacrimal
      intubation system in the treatment of congenital nasolacrimal duct obstruction.
      METHODS: In this retrospective cases series, 148 patients (187 eyes) with
      congenital nasolacrimal duct obstruction between 2006 and 2007 from Beijing
      Children's Hospital, whose age ranged from 5 to 40 months (average 13 months),
      underwent silicone intubation with the Ritleng lacrimal intubation system, who
      received unsuccessful probing procedure previously. The therapeutic effect
      including dacryorrhea disappearance and lacrimal passages excretory function
      regaining was observed and the complications such as epistaxis, lacrimal duct
      edema or silicone tube prolapse were recorded. The follow-up period was from 4 to
      17 months (average 11 months). RESULTS: Dacryorrhea disappeared in 157 eyes
      (84.0%) within 1 - 3 days after the surgery. The tubes were left in the place for
      3 or 6 months. All the 187 eyes were successfully taken out of tubes. As follow
      up, the overall successful rate was 95.2% (178/187). Seven eyes (3.7%) relief
      from symptoms and two eyes (1.1%) were ineffective. 46 cases (52 eyes), whose
      ages were about 5 months, regained normal lacrimal passages excretory function
      within 1 month after surgery. Complication included epistaxis (9 eyes) and
      lacrimal duct edema (9 eyes). The silicone tube prolapsed in eight eyes (4.3%).
      CONCLUSIONS: The Ritleng lacrimal intubation system is an easy, effective and
      nontraumatizing procedure for the treatment of congenital nasolacrimal duct
      obstruction. The lacrimal intubation procedure offers an early and active
      treatment for congenital nasolacrimal duct obstruct patients.

PMID- 19176116
TI  - [Clinical investigation of the Heidelberg retina tomograph II in assessment of
      macular edema].
AB  - OBJECTIVE: To evaluate the significance of detecting macular edema by the Retina
      Module of the Heidelberg retina tomograph II (HRTII). METHODS: Comparative
      clinical study, One hundred and twenty-six eyes were divided into two groups
      according to FFA results, one with macular edema and the other without macular
      edema. Morphological changes in macular edema were observed by HRTII and e (edema
      index) in two areas of each eye were determined. E value in these two groups and
      the correlation of e with retinal thickness, BCVA, amplitude and latency of N1
      and P1 by multifocal electroretinogram were analyzed. RESULTS: HRTII-RM scan
      could distinguish different kinds of macular edema (cystoid, local and diffused)
      and the difference of e between these two groups was significant (e1: t = 
      19.238, e2: t = -12.436; P < 0.01). The best critical value of e was 1.475 and
      1.411 (e1 = 1.475, e2 = 1.411). The sensitivity of e was 92.9% and 91.8% (e1 =
      92.9%, e2 = 91.8%). The specificity of e was 97.6% and 95.1% (e1 = 97.6%, e2 =
      95.1%). The correlation coefficient between e and retinal thickness was 0.816 and
      0.587 (e1: r = 0.816, e2: r = 0.587; P < 0.01); was -0.658 and -0.640 (e1: r = 
      0.658, e2: r = -0.640; P < 0.01) between e and BCVA; was 0.266 and 0.312 (e1: r =
      0.266, e2: r = 0.312; P < 0.01) between e and latency of N1; was -0.609 and 
      0.586 (e1: r = -0.609, e2: r = -0.586; P < 0.01) between e and amplitude of N1;
      was 0.529 and 0.431 (e1: r = 0.529, e2: r = 0.431; P < 0.01) between e and
      latency of P1 and was -0.783 and -0.714 (e1: r = -0.783, e2: r = -0.714; P <
      0.01) between e and amplitude of P1, respectively. CONCLUSIONS: There are
      characteristic changes in the appearance of macular edema as examined by HRT II
      RM. The quantitative index e value also shows remarkable changes. HRT II-RM not
      only detects morphological changes, but also relates to functional changes. This
      method is capable for evaluating the macular edema.

PMID- 19176117
TI  - [Intraocular lens power calculation after corneal refractive surgery].
AB  - OBJECTIVES: To investigate the effective method for the calculation of
      intraocular lens power retrospectively from post-LASIK cases. METHODS: It was a
      retrospective case series. 40 eyes of 28 patients (14 male and 14 Female) had the
      Phacoemulsification post-LASIK in HongKong Sanitorium & Hospital; the age ranged
      from 41.00 to 69.00 years ages, (50.68 +/- 6.56) years. LASIK was done from
      January, 1997 to April, 2005. Phacoemulsification was done from October, 2000 to
      September, 2005. RESULTS: Average axial length was (28.06 +/- 1.98) mm (rang from
      24.28 to 31.96 mm). The initial refraction power (Spherical Equivalent, SE)
      before LASIK was from -3.13 to -18.00 D, (-10.44 +/- 3.93) D. K value pre-LASIK
      was 41.40 to 46.90 D, (43.57 +/- 1.47) D. The best corrected visual acuity (BCVA)
      preLASIK was 20/20 in 19 eyes, 20/25 in 10 eyes, 20/30 in 7 eyes and 20/40 in 4
      eyes. The refraction power of 6 months post-LASIK (SE) was -2.83 to +1.25 D, (
      0.32 +/- 0.95) D. The refraction power pre-phaco (SE) was -5.75 to +1.13 D, (
      2.35 +/- 2.16) D. The calculated K1 (KpreLASIK-RpostLASIK + RpreLASIK) was 27.60
      to 40.70 D, (34.62 +/- 3.56) D. The K from the IOLmaster (K2) was 32.39 to 43.53
      D, (38.04 +/- 2.45) D. The target refraction of K1 was -3.69 to 0.61 D, (-1.32 +/
      1.00) D, the target refraction of K2 was -3.67 approximately 3.95 D, (-0.60 +/-
      1.84) D. There was significant difference between these two target refraction, (t
      = -2.40, P = 0.02). The refraction power of post-phaco (> 3 months) was -4.50 to
      +1.75 D, (-1.10 +/- 1.51) D. The BCVA post-Phaco was 20/20 in 20 eyes, 20/25 in 9
      eyes, 20/30 in 5 eyes and 20/40 in 6 eyes. CONCLUSIONS: The formula used in the
      study for the calculation of intraocular lens power is accurate and effective.

PMID- 19176118
TI  - [Expression and significance of telomerase activity of lens epithelial cells in
      posterior capsule opacification of rabbits].
AB  - OBJECTIVE: To explore the expression of telomerase activity of the lens
      epithelial cells in posterior capsule opacification of rabbits. METHODS: Clear
      corneal tunnel phacoemulsification was performed in both eyes of 11 New Zealand
      rabbits. After the model of posterior capsule opacification succeed in all eyes.
      Then, telomerase activity of the lens epithelial cells in the equator and
      posterior capsule opacification of 20 eyes was detected with TRAP-ELISA and TRAP
      PAGE techniques. RESULTS: HepG2 cells were used as positive controls. Telomerase
      activity was detected in the lens epithelial cells in the equator capsule and
      posterior capsule opacification in rabbits, which showed several dim gradient
      stripped electrophoresis pattern. A450 - 690 value of telomerase activity in the
      equator capsule and posterior capsule opacification was 0.85 +/- 0.23 and 0.67 +/
      0.19, respectively, indicating statistically significant difference (t = 2.526,
      0.021; P < 0.05). CONCLUSIONS: Telomerase activity exists in the lens epithelial
      cells of posterior capsule opacification in rabbits. The telomerase activity in
      this area is lower than that in the equator capsule.

PMID- 19176119
TI  - [To knockdown survivin gene expression by siRNA in SO-Rb50 cells].
AB  - OBJECTIVE: To investigate cell proliferation and apoptosis status of human
      retinoblastoma cell line SO-Rb50 after knockdown of Survivin gene by means of
      small interfering RNA (siRNA). METHODS: Survivin specific siRNA designed from the
      human gene sequence and nonsense siRNA (as a negative control) was transfected
      into SO-Rb50 cells. The inhibition of the expression of Survivin mRNA and protein
      levels were detected by reverse transcription-polymerase chain reaction (RT-PCR)
      and Western blot. Proliferation inhibition rate of SO-Rb50 cells was analyzed by
      MTT assay. Apoptotic rate and cell cycle were analyzed by flow cytometry (FCM)
      and the apoptotic morphology was observed by fluorescent microscope. RESULTS: The
      expression of Survivin at both mRNA and protein level in specific siRNA group
      decreased significantly in comparison with untransfected group and nonsense siRNA
      group after 24 hours of transfection. The proliferation of SO-Rb50 was inhibited
      in the Survivin specific siRNA group at the concentrations of 35, 70 and 100
      nmol/L (P < 0.05). Flow cytometry showed obvious apoptotic peak in Survivin
      specific group with an accumulation of cells in the G0/G1 phase and a decrease in
      G2/M phase and S phase. Typical apoptosis morphology was also observed under
      fluorescent microscope. CONCLUSIONS: Survivin specific siRNA could inhibit SO
      Rb50 cell proliferation and induced apoptosis by knockdown of Survivin gene. Our
      data suggests that the use of Survivin-specific siRNA deserves further
      investigation as a novel approach to retinoblastoma therapy.

PMID- 19176120
TI  - [Observation on the morphology differences of ocular rectus pulley between
      preschool children and adults].
AB  - OBJECTIVE: To study the morphology differences of ocular rectus muscles pulley
      between preschool children and adults. METHODS: It was an experimental research.
      Ten fresh cadaver orbits (five children and five adults) were fixed in situ and
      serially sectioned at 4 microm thickness. Every section was stained with Masson's
      trichrome and picrosirius red methods. After being stained, extraocular muscle
      pulley in typical sections was examined through gross anatomy and light
      microscopy. Two-factor analysis of variance for quantitative data was used in
      statistical treatment. RESULTS: Near the equator of the globe, the children and
      adults' extraocular muscle pulleys were all at the points where the rectus
      penetrate posterior Tenon's fascia, encircling the rectus orbit side by fiber
      ring structure. There were pulley bands among rectus pulleys. The rectus pulley
      length and the origin distance from the corneoscleral limbus of the children were
      significantly less than those from the adult group (P < 0.05). The main
      composition of the children rectus pulley was similar to that of the adults, but
      the smooth muscle and collagen type III fibers contents of the medial rectus
      pulley in children were significantly greater than those in the adults group (P <
      0.05). Collagen type I fibers in the children were significantly less than that
      of the adults group (P < 0.05). CONCLUSION: There are morphological differences
      in rectus pulley between preschool children and adults, which provides an
      anatomic basis for the better understanding of the pathogenesis of strabismus.

PMID- 19176121
TI  - [Mechanism of arsenic trioxide induced apoptosis in cultured human lens
      epithelium cells].
AB  - OBJECTIVE: To study cytotoxic effects of arsenic trioxide (As2O3) on the human
      lens epithelium cells and to identify the biological mechanism for these effects.
      METHODS: In this experimental study, human lens epithelium cells (FHL124 cells)
      were cultured in Eagle's minimum essential medium supplemented with 5% fetal calf
      serum. The effects of As2O3 on FHL124 cells growth were tested by MTT, and
      apoptosis was detected by TUNEL assay. Gene changes were detected by real-time
      PCR (Taqman). As2O3-induced changes in cell calcium level were measured by real
      time fluorometric single-cell digital imaging techniques after Fura-2
      incorporation. RESULTS: As2O3 inhibited the growth of FHL 124 cells in vitro in a
      dose-dependent manner, given an IC50 value of 1.5 micromol/L. As2O3 induced
      apoptosis of FHL124 cells as showed by TUNEL assay. As2O3 provoked an endoplasmic
      reticulum (ER) stress response identified through an up regulation of EIF2A, ERN1
      and ATF6 (F = 8.51, P = 0.0005). As2O3 depleted the calcium store and
      consequently lead to a decrease of calcium signaling (P = 0.0018). Moreover,
      As2O3 had a moderate effect on the calcium influx pathway. CONCLUSIONS: As2O3
      inhibits the growth and induces apoptosis of human lens epithelium cells. As2O3
      provokes an ER stress which could be the cause of apoptic processes.

PMID- 19176122
TI  - [Inhibitory effect of interfering RNA targeting HIF-1alpha and VEGF on retinal
      neovascularization in the mouse].
AB  - OBJECTIVE: To evaluate the inhibitory effect of small interfering RNA (siRNA) on
      the expressions of hypoxia inducible factor-1alpha (HIF-1alpha) and vascular
      endothelial growth factor (VEGF) in retinal neovascularization in the mouse.
      METHODS: HIF-1alpha siRNA recombinant plasmid was constructed. Liposome mediated
      the expressive plasmid of enhanced green fluorescent protein (EGFP) pEGFP-N1
      complex was injected into the vitreous of C57BL/6J mice. The expression of GFP
      was observed in retinal flat-mounts one day after injection. Randomized
      controlled trial was performed. There were totally ninety (seven-day-old)
      C57BL/6J mice in which seventeen mice were chosen as normal group and seventy
      three mice were divided into five groups randomly including control model group,
      vector group and gene therapy group (HIF-1alpha siRNA group, VEGF siRNA group and
      co-transfection group), in which retinal neovascularization was induced by
      hypoxia. Liposome with vector plasmid, HIF-1alpha siRNA and VEGF165 siRNA were
      injected into the vitreous in the vector group, HIF-1alpha siRNA group and VEGF
      siRNA group respectively one day before mice were moved out to room air from the
      cabin. Liposome with HIF-1alpha siRNA and VEGF165 siRNA was injected in the co
      transfection group at the same time point. Fluorescent angiography was used to
      assess the vascular pattern. The proliferative neovascular response was
      quantified by counting the nuclei of new vessels extending from the retina into
      the vitreous in cross-sections. HIF-1alpha and VEGF levels in retinas were
      measured by reverse transcriptase-polymerase chain reaction and Western blot.
      Significant differences between groups were evaluated by one-way analysis of
      variance, followed by a least-significant difference analysis. RESULTS: The GFP
      expression in retinal cells was observed one day after injection of liposome
      mediated pEGFP-N1 complex. Neovascular tufts and fluorescein leakage were
      decreased in gene therapy group especially in co-transfection group compared to
      the control model group. The neovascular nuclei were decreased in gene therapy
      group [HIF-1alpha siRNA group (27.73 +/- 2.33), VEGF siRNA group (15.43 +/-
      3.23), co-transfection group (8.70 +/- 2.88)] compared to the other three groups
      (F = 3016.537, P < 0.01). The expression of HIF-1alpha mRNA and protein in
      retinas were increased in control model group (1.08 +/- 0.06, 0.383 +/- 0.009)
      and vector group (1.09 +/- 0.05, 0.386 +/- 0.010) as compared with normal group
      (0.81 +/- 0.07, 0.035 +/- 0.003), while decreased 57.4% and 52.5% respectively in
      the HIF-1alpha siRNA group (0.46 +/- 0.06, 0.182 +/- 0.008) as compared with
      control model group (F = 139.804, 2686.001; P < 0.01). The expression of VEGF
      mRNA and protein in retinas were increased significantly in control model group
      (1.53 +/- 0.07, 0.340 +/- 0.004) and vector group (1.59 +/- 0.06, 0.337 +/-
      0.009) as compared with normal group (0.27 +/- 0.08, 0.051 +/- 0.008), while
      decreased significantly in gene therapy group especially co-transfection group
      (decreased 85.6% and 80.9% respectively) as compared with control model group (F
      = 421.423, 2513.583; P < 0.01). CONCLUSIONS: HIF-1alpha siRNA and VEGF165 siRNA
      can inhibit retinal neovascularization in the mouse effectively. Co-transfection
      of these two siRNAs shows the greatest inhibitory effect.

PMID- 19176123
TI  - [Inhibition of corneal neovascularization by vascular endothelial growth
      inhibitor gene].
AB  - OBJECTIVE: To evaluate the effect of Effectene lipofectene mediated plasmids
      encoding human pcDNA4-vascular endothelia growth inhibitor (pcDNA4-VEGI) gene on
      corneal neovascularization (CNV). METHODS: It was an experimental study. Forty
      healthy New Zealand albino rabbits (40 eyes) were divided into 4 teams according
      to the random digits table: team A (10 rabbits) was the team which transfected by
      lipofectine mediated plasmids encoding human pcDNA4-vascular endothelia growth
      inhibitor (pcDNA4-VEGI) gene; team B (10 rabbits) was the team transfected by
      empty vector; team C (10 rabbits) was the team transfected by lipofectine; team D
      (10 rabbits) was the empty control group which was transfected by saline. (1)
      Human VEGI gene fragment was connected with expressional vector plasmid pcDNA4 to
      construct the pcDNA4-VEGI gene expression vector. Computer automatic sequence
      analysis was used to identify the gene. (2) New Zealand albino rabbits were
      sutured by 5 - 0 silk in the superior cornea to establish the animal model and
      were transfected by pcDNA4-VEGI gene mediated by Effectene lipofectene
      transfection. Length and area of CNV were measured by slit lamp every day after
      transfection, immunohistochemistry was used to detected the expression of VEGI
      protein in cornea at the time 3, 7, 14 and 21 d. RESULTS: (1) Computer automatic
      sequence analysis confirmed the correct recombination of pcDNA4-VEGI gene. (2)
      Average occurrence of CNV in the pcDNA4-VEGI gene transfected team was 6.3 days
      while that in the control teams were 3.1, 3.2, 3.2 days (F = 39.838, P < 0.01).
      Average length and area of CNV were also different in the VEGI team and the
      control teams (q between team A and B on average length of CNV was 17.386, 20.944
      and 8.892 on 7, 14 and 21 d; q between team A and C on average length of CNV was
      19.488, 19.795 and 7.483 on 7, 14 and 21 d; q between team A and C on average
      length of CNV was 19.583, 20.413 and 8.941 on 7, 14 and 21 d, and P were all <
      0.01. And q between team A and B on average area of CNV was 30.238, 57.820 and
      35.543 on 7, 14 and 21 d; q between team A and C on average area of CNV was
      32.607, 57.843 and 36.653 on 7, 14 and 21 d; q between team A and C on average
      area of CNV was 33.873, 57.590 and 34.724 on 7, 14 and 21 d, and P were all <
      0.01). Integrated epithelium, light stroma edema, less CNV and less inflammation
      could be seen in the gene-therapy team. And immunohistochemistry results showed
      VEGI positive cells in epithelium, stroma, endothelium and the cliff of CNV in
      the gene therapy team. CONCLUSIONS: PCR, enzyme cutting, recombination and other
      genetic techniques could be used to construct expressional pcDNA4-VEGI gene.
      Effectene lipofectene transfection technique could be effectively used in
      transfecting pcDNA4-VEGI gene into rabbit cornea to inhibit CNV.

PMID- 19176124
TI  - [Biocompatibility of acellular corneal stroma and transplantation of tissue
      engineered corneal epithelium].
AB  - OBJECTIVE: To evaluate the biocompatibility of xenogeneic acellular corneal
      stroma, the feasibility of tissue engineered corneal epithelial transplantation,
      and verify the long term survival of epithelial allograft. METHODS: It was a
      experimental study. Porcine corneal stroma was treated by dispase followed by
      Triton-X-100 detergent. Treated porcine corneal stroma (group A) or fresh corneal
      stroma (group B) were put into the sac of rabbit cornea. Rabbit cornea without
      implantation of porcine corneal stroma was used as the control group (group C).
      Immunological rejection was evaluated in morphology, histopathology and
      immunohistochemistry in month 1, 3, 6. Female rabbit underwent lamellar
      keratoplasty (LK) using male tissue engineered corneal epithelium as donors, and
      immunological rejection after LK was analyzed. The corneas were collected at day
      1, 3, 7, 15 and 30 after LK and evaluated by histopathology, immunohistochemistry
      and sex-determining region of Y-chromosome (SRY)-PCR analysis. RESULTS: All
      corneas became transparent gradually after the transplantation of treated porcine
      corneal stroma and were not rejected. The epithelium, stroma, endothelium,
      Bowman's and Descemet's membrane were preserved in all corneas of group A and B
      in histological observations, collagen fibers were parallel, a few keratocytes
      presented in the acellular and fresh corneal stromas. The corneas of group C were
      normal in histological sections. No significant immune rejection was noted in any
      of the corneas. The corneas in the study of transplantation of tissue engineered
      cornea epithelium recovered smoothly in 3 or 4 days, turned transparent in 15 or
      20 days after surgery and were not stained by fluorescein. Well-differentiated
      corneal epithelium were recognized at 15 and 30 days after LK. Many keratocytes
      infiltrated into the scaffold. SRY-PCR analysis showed that allogenic donor
      corneal epithelium cells could survive in recipients after a long-term
      observation. CONCLUSIONS: Acellular porcine corneal stroma shows a satisfying
      biocompatibility. Tissue engineered corneal epithelium using acellular porcine
      corneal stroma as carrier could be used as donors for LK with satisfactory
      results. Donor cells have the potential to survive in recipients after long-term
      observation.

PMID- 19176129
TI  - [Recent advances in studies of clinical treatment of uveitis].
AB  - Uveitis is a common immune-related intraocular inflammation, the topical or
      systemic corticosteroids are the first-line drugs for the treatment of uveitis.
      The combined immunomodulatory agents of cyclosporine, mycophenolate mofetil,
      azathioprine or cyclophosphamide are helpful for the treatment of severe or
      refractory uveitis. The new biologic agents, tumor necrosis factor inhibitors,
      interferon alpha or the interleukin-2 receptor antagonists, are also helpful for
      certain types of refractory uveitis. Intravitreal steroids injection or
      vitrectomy would be beneficial for specific types of uveitis and their
      complications. The advances of uveitis treatment in recent years are reviewed.

PMID- 19176130
TI  - [Cortical plasticity in blind individual].
AB  - The cognitive mechanisms and functional brain imaging research on blind
      individuals provide special information for exploring the plasticity of the
      developing human brain. This paper focuses on five aspects of recent progress in
      this field: (1) the behavior compensation of the blind; (2) the influence of
      early visual deprivation and later visual deprivation on cross-modal
      reorganization; (3) the relationship between the complexity of task requirement
      and cross-modal reorganization; (4) the relationship between the sensitive
      periods of the visual system and the time course of cross-modal reorganization;
      (5) the neural mechanisms of cross-modal reorganization. These findings
      contribute greatly to the theoretical basis of the rehabilitation of individuals
      with perceptual deficits.

PMID- 19176132
TI  - [Deal with food safety emergency using risk analysis principle].

PMID- 19176133
TI  - [Post-disaster psychological crisis intervention].

PMID- 19176137
TI  - [Application of the triage assessment system for a rapid assessment of mental
      health of the referral wounded and their family members in Wenchuan earthquake].
AB  - OBJECTIVE: To quickly assess the psychological status of the wounded who were
      transferred in the earthquake and their family members, as to promoting the
      system of psychological crisis intervention. METHODS: The triage assessment
      system was used to the 44 wounded and 37 family members, additionally, the
      Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA)
      for related analysis were also administrated to verify the effectiveness of
      screening of the triage assessment system. RESULTS: Of the 79 wounded and their
      families in the triage assessment system, the score of emotion in the wounded
      group was (3.07 +/- 1.38), the score of cognition was (2.34 +/- 1.39), the score
      of behavior was (2.71 +/- 1.47), and the total score was (8.12 +/- 3.69); the
      score of emotion in the family group was (2.51 +/- 1.27), the score of cognition
      was (1.57 +/- 0.85), the score of behavior was (1.71 +/- 1.02), and the total
      score was (5.80 +/- 2.61). There were significant differences in the family and
      the wounded group in cognition, behavior and the total (t(cognition) = 2.853, P =
      0.006; t(behavior) = 3.366, P = 0.001; t(total) = 3.116, P = 0.003). Both the
      depression and anxiety symptoms in the Hamilton Depression Scale (HAMD) and
      Hamilton Anxiety Scale (HAMA) were 11.48 +/- 7.62, 9.23 +/- 5.64, and 8.49 +/-
      4.87, 9.38 +/- 7.05, respectively. In the emotion, cognition, behavior and total
      scores of the triage assessment system related to higher with HAMD and HAMA were
      r(emotion-HAMD) = 0.393, P = 0.001; r(emotion-HAMA) = 0.443, P = 0.000;
      r(cognition-HAMD) = 0.434, P = 0.000; r(cognition-HAMA) = 0.240, P = 0.037;
      r(behavior-HAMD) = 0.529, P = 0.000; r(behavior-HAMA) = 0.256, P = 0.026; r(total
      HAMD) = 0.517, P = 0.000; r(total-HAMA) = 0.369, P = 0.001. CONCLUSION: The
      triage assessment system should be the reliable method for an assessment featured
      by a rapid, accurate and simple one in screening and monitoring.

PMID- 19176138
TI  - [Prevalence and predictors of acute stress disorder after earthquake: findings
      from Wenchuan earthquake in China].
AB  - OBJECTIVE: To investigate the prevalence and predictors of acute stress disorder
      (ASD) in the victims affected by Wenchuan earthquake in China. METHODS: A random
      clustered sampling method was used. Of 891 victims enrolled in the study, 874
      were completely assessed with the ASD constructive questionnaire and diagnosed
      with DSM-IV criteria. Sociodemographic variables were obtained. Also, the major
      symptoms of ASD (i.e., general symptoms to a traumatic event; dissociative
      symptoms; re-experiencing symptoms; hyper-arousal symptoms; avoidance symptoms)
      were recorded. RESULTS: The incidence rate of ASD was 12.59% (110/874). The
      incidence rates of ASD for female and male were 15.16% (72/475) and 9.52%
      (38/399) respectively. There was a significant difference between female and male
      on the incidence rate of ASD (chi(2) = 6.26, P = 0.01). Logistic regression
      indicated that the ASD diagnosis was predicted by gender (beta = 0.58, P = 0.01,
      OR = 1.79), the condition of casualties of family members (beta = 0.60, P = 0.01,
      OR = 1.82), and the condition of sharp properties loss (beta = 1.02, P = 0.01, OR
      = 2.76). CONCLUSION: The major earthquake should have great influence on mental
      health of victims. The efforts to reduce casualties and property loss might help
      to prevent ASD. Further research is needed on gender difference among traumatic
      events.

PMID- 19176139
TI  - [A comparative study on mental health among students and adults in the earthquake
      hit areas].
AB  - OBJECTIVE: To understand mental health status of the students and adults in the
      earthquake disaster areas, as to providing guidance on intervention for post
      disaster psychological crisis. METHODS: The Self-Reporting Questionnaire (SRQ
      20), an appendix of The Ministry of Health of "emergency psychological crisis
      intervention guiding principles", was used among 1222 victims in Wenchuan
      earthquake, Sichuan province. This questionnaire survey was conducted in 729
      students and 493 adult victims in a randomized method. Of the 734 questionnaires
      distributed and received in students, 729 were validly responded with efficiency
      rate of 99.32%; while for adults, 496 questionnaires distributed, 496 received,
      493 were valid with efficiency rate of 99.39%. RESULTS: (1) In students victims,
      65% responded that they did feel "uneasy, nervous or worried", followed by "easy
      to be scared", "feel unhappy", "easy fatigue" and "hard to make a decision". For
      adult victims, 80.5% replied that they felt "uneasy, nervous or worried",
      followed by "feel unhappy", "easy fatigue", "difficult sleeping", "easy to be
      scared". (2) The average of the SRQ score of student victims was 6.58 +/- 3.99,
      and 6.07 +/- 4.02 for males, 7.03 +/- 3.91 for females. The average of the SRQ
      score of student victims was 7.36 +/- 3.98, male 6.68 +/- 3.82, female 7.99 +/-
      4.03. The significant differences (t(women) = 2.985, P < 0.01; t(total) = 3.332,
      P < 0.01) was observed in women and the total group of students and adults. (3)
      The SRQ positive screening rate of students group was 46.50%, the adult group was
      52.33%, SRQ >or= 7 points and SRQ < 7 sub-group of students and adults of the
      total score there were significant differences (t(1) = 39.771, P < 0.01; t(2) =
      31.961, P < 0.01). SRQ >or= 7 sub-group of students and adult women in between
      there was a significant difference (t = 23.641, P < 0.01), SRQ < 7 sub-group of
      students and adults in general and women there were significant differences (t(1)
      = 3.092, P < 0.01; t(2) = 2.911, P < 0.01). (4) SRQ scores with gender and age
      had had a positive relation (r(SRQ total-sex) = 0.118, P = 0.000; r(SRQ total
      age) = 0.103, P = 0.000). CONCLUSION: The emotional suffering symptoms of
      students victims and adult victims should be "nervous, unhappy, vulnerable on
      issues such as fatigue", the adult group had a higher symptom rate than the group
      of students, the mental health was more serious than that of students, as
      influenced by some factors including age and gender. Students, being a special
      population group should be paid more attention to focusing a designated behavior
      intervention, as a planned manner of intervention.

PMID- 19176140
TI  - [Reliability and validity of the self-reporting questionnaire for assessing
      mental health applied in Wenchuan earthquake].
AB  - OBJECTIVE: To detect the reliability and validity of the self-reporting
      questionnaire (SRQ-20), and to make a rapid assessment on mental health among
      victims in sudden crisis. METHODS: The SRQ-20 which is on appendix of the
      Ministry of Health adopted as "emergency psychological crisis intervention
      guiding principles" was administrated among 1222 victims in Wenchuan earthquake.
      The reliability of the questionnaire was tested by split-half coefficient and
      Cronbach's alpha coefficient; the validity was tested by means of principal
      component factor analysis. RESULTS: The self-reporting questionnaire and split
      half coefficient was 0.748, each item of Cronbach's alpha in the reliability
      coefficient was between in 0.778 to 0.789, overall Cronbach's alpha in the
      reliability coefficient was 0.792. There were five main components in principal
      component factor analysis: lacking of power, somatization/biological symptoms,
      depression thought, emotions and awareness. CONCLUSION: The self-reporting
      questionnaire (SRQ-20) should have good reliability, and validity, and China's
      psychological crisis intervention in processing assessment of the mental health
      should be a fast, accurate and effective screening tool.

PMID- 19176141
TI  - [Emergency prophylactic effects of the avian influenza virus immunized serum on
      the infected mice].
AB  - OBJECTIVE: To evaluate emergency prophylactic effects of the avian influenza
      virus immunized serum on experimentally infected mice. METHODS: Serum HI antibody
      titers of 30 mice were detected at day 1 to 19 after being inoculated with 0.2 ml
      immune serum to estimate half life of immune serum. Ten mice clinical symptom was
      recorded to estimate the serum security after mice injected 1.5 ml immune serum.
      Seventy mice were randomly divided into 7 groups according to random number table
      and inoculated with 0.2 ml, 0.1 ml and 0.05 ml immune serum respectively via
      intraperitoneal injection on day 8, 4 and 1 prior to challenged with 10 LD(50)
      influenza virus intranasal. Mice were observed continually for 14 days to
      calculate the morbidity, mortality, average survival days and compare the lung
      index and viral titers in lung. RESULTS: Serum HI antibody titers of mice which
      inoculated with 0.2 ml immune serum maintained 2(6) in 15 days after injection,
      but drawdown after day 17, the mice injected 1.5 ml immune serum were all alive
      and none onset. The survival rate of mice which injected 0.2 ml serum on the day
      8, 4, 1 before challenge was 80%, 100% and 100%, and the average survival period
      was 13.1 days, 14.0 days and 14.0 days respectively. The survival rate of mice
      which injected 0.1 ml and 0.05 ml serum on day 1 before challenge was 100% and
      50%, and the average survival days were 14.0 days and 11.7 days respectively. The
      mice lung index of experimental groups (0.0096 +/- 0.0033 - 0.0145 +/- 0.0060)
      was smaller than that of viral control group (0.0199 +/- 0.0025), with a
      statistical significance (P value 0.0022 - 0.0470, < 0.05). The viral titers in
      lung were significantly decreased by 2 titer as compared to the viral controls.
      CONCLUSION: The avian influenza virus immunized serum might contain the emergency
      prophylactic effects and could be developed as an agent for possible human-avian
      influenza pandemic.

PMID- 19176142
TI  - [The study of insulin resistance and leptin resistance on the model of simplicity
      obesity rats by curcumin].
AB  - OBJECTIVE: To evaluate the insulin and leptin resistance of curcumin on
      simplicity obesity rats. METHODS: All 50 SPF grade healthy Sprague-Dawley male
      initial weaning rats were used for two groups in stratified sampling by weight:
      30 in treated group and 20 in control group. They were assigned to the following
      treatment for 8 weeks: the treated group was fed with high-fat food and the
      control group was fed with normal food. Eight weeks later, adiposity model rats
      were prepared. Groups: adiposity model rats were divided into 3 groups: model +
      low curcumin (1.25 g/kg), model + high curcumin (5.00 g/kg) and a model group. In
      addition, there also had a normal control and a control + high curcumin (5.00
      g/kg) group. Ten rats in every group and all given ground feed. After
      intragastric administration in different doses of curcumin 4 weeks, the effects
      and pathological changes were observed by the blood sugar, insulin, leptin and
      TNF-alpha, pathology and transmission electron microscope of pancreatic gland.
      RESULTS: Given 4 weeks the different dose of curcumin on the simplicity obesity
      rats, the significant diminished weight (435.0 +/- 37.6) g and content of
      lipocyte (4.78 +/- 1.87) g as compared with the obesity model control (492.3 +/-
      14.8) g and (8.94 +/- 1.88) g (t values were 4.484 and 4.961 respectively, P <
      0.01), level of blood sugar (4.50 +/- 0.09) mmol/L, insulin (7.43 +/- 0.65)
      mmol/L, leptin (3.40 +/- 0.39) mmol/L and TNF-alpha (2.42 +/- 0.19) ng/ml were
      significantly decreased than those of adiposity model rats (4.94 +/- 0.12)
      mmol/L, (9.30 +/- 0.21) mmol/L, (4.40 +/- 0.23) mmol/L and (2.86 +/- 0.49) ng/ml
      (t values were 8.297, 7.743, 6.247 and 2.368 respectively, P < 0.05), and there
      was no significant difference with the control group (4.30 +/- 0.14) mmol/L on
      the level of blood sugar (t = 0.399, P > 0.05). There were a lot of secretory
      granules with large sphere volume in beta cells of pancreatic island found by
      transmission electron microscope, and these secretory granules had a higher
      electron density than those in non-disposed groups. CONCLUSION: By diminishing
      the sediment of fat, relaxing the lymphatic return, and refraining the apoptosis
      of beta cells, the curcumin might significantly decrease the level of insulin
      resistance and leptin resistance caused by the high fat diet.

PMID- 19176143
TI  - [Analysis on influence factors of dietary supplement used in population aged
      above 45 years in Beijing].
AB  - OBJECTIVE: To explore influence factors of dietary supplement used in population
      aged above 45 years in Beijing. METHODS: Utilizing the data of the survey of
      dietary supplement (DS) used in Beijing in 2006 was to investigate the influence
      factors by using multi-factorial logistic regression analysis. RESULTS: All 2487
      samples were included in the analysis. Sex, age, average income of each month for
      each member of the family, experiences of deficiency of nutrition, attitude to
      nutrition knowledge, attitude to the need of DS and city-or-rural resident had
      shown effects on DS using. The percentage of using DS in female was higher than
      that in male being 19.3% and 11.8% respectively. The percentage grew up as the
      age became older. The same trend appeared as the economic-status going up, but
      not as education level change. Use of DS was greater in urban population (16.9%)
      than in rural population (14.6%). The percentage of using DS in people who had or
      just been diagnosed as malnutrition/deficiency disease or chronic disease, or
      those who thought themselves having got these diseases only by their own feeling
      were higher than those did not. CONCLUSION: People the female, the elder, or
      those having higher income, having experiences of deficiency of nutrition, are
      more interested in nutrition knowledge, and more positive in need of DS and those
      living in rural should be the target population of nutrition education for DS
      use.

PMID- 19176144
TI  - [Application of pulsed-field gel electrophoresis in a food-borne outbreak of
      Salmonella serotype Muenchen infection].
AB  - OBJECTIVE: To investigate the application of pulsed-field gel electrophoresis
      (PFGE) in food-borne outbreak. METHODS: Pathogens were isolated and further
      characteristics identified by traditional methods. The strains isolated were
      carried out with molecular typing with using PFGE. PFGE was performed by
      Laboratory Directions for molecular subtyping of Salmonella by PFGE (CDC, USA)
      and the results of PFGE were analyzed by BioNumerics soft. RESULTS: Totally 14
      Salmonella serotype Muenchen strains were isolated from 19 patients, 3 of 9
      suspicious foods were positive for S. muenchen and 7 strains were isolated from
      18 cooks. The biochemistry characterization and antimicrobial susceptibility of
      all the strains isolated were the same. 23 S. muenchen isolates were all shown
      indistinguishable by PFGE. CONCLUSION: PFGE should play a key role in identifying
      the outbreak-associated isolates and distinguishing them from unrelated sporadic
      isolates. It might also demonstrate that the genetic fingerprints of serotype
      Muenchen isolates derived from patients were indistinguishable from those derived
      from drinks. PFGE might provide precise information on bacterial food-borne
      pathogens, promptly identify the source of infection, and effectively prevent
      from spreading. It should be one of the early warning method on controlling
      outbreak of the food-borne disease.

PMID- 19176145
TI  - [Application of nano-sized TiO2 photocatalysis to air purification and
      sterilization].
AB  - OBJECTIVE: To develop and evaluate the efficiency of air purification and
      sterilization instrument based on nano-sized TiO(2) photocatalytic technique.
      METHODS: The nano-sized TiO(2) photocatalytic air purification and sterilization
      instrument was designed and a sample had been prepared. The sterilization
      efficiencies for E.coli and Klebsiella by the nano-sized TiO(2) photocatalytic
      instrument and ultraviolet (UV) were measured in closed labs. The on-site
      efficiency of the instrument was evaluated, too. RESULTS: The nano-sized TiO(2)
      photocatalytic air purification and sterilization instrument was composed of five
      units: rough filter, nano-sized TiO(2) photocatalytic unit, activated carbon
      fiber filter, negative ion generator, and programmed control unit. The E.coli
      killing rates by the nano-sized TiO(2) photocatalytic instrument were 76.0%,
      81.8%, 77.5%, and 80.7% at 30, 60, 90, and 120 minutes, respectively. There was
      no significant difference between the E.coli killing rates of the instrument and
      UV (P > 0.05), except the 120 minutes timepoint. The Klebsiella killing rates by
      the instrument were 78.4%, 79.5%, 67.3%, and 58.5% at 30, 60, 90, and 120
      minutes, respectively. The Klebsiella killing efficiencies of the instrument at
      30 and 60 minutes were better than that of UV (P < 0.01). There was no
      significant difference between the Klebsiella killing efficiencies of the
      instrument and UV (P > 0.05). CONCLUSION: The air sterilization efficiency of the
      nano-sized TiO(2) photocatalytic instrument should be equivalent or better as
      compared with the UV. This instrument might be used for the air purification and
      sterilization of the public locations.

PMID- 19176154
TI  - [Why was my article refused?].

PMID- 19176155
TI  - [Heat stroke and burns resulting from use of sauna].
AB  - We describe a case of severe heat stroke resulting from exposure to extreme heat
      in a sauna for an unknown period of time. The patient sustained 20% 2nd degree
      burns. On arrival at the emergency department, the patient's temperature was 40.5
      degrees C. At the critical care unit, the patient developed severe multi-organ
      failure and critical polyneuropathy. Severe heat stroke is a rare diagnosis in
      Denmark. The treatment is symptomatic and the prognosis is grave, especially in
      combination with severe burns.

PMID- 19176156
TI  - [Adenomatoid tumour of the adrenal gland].
AB  - An adenomatoid tumour in the right suprarenal gland was discovered during
      clinical cancer staging of a 73-year-old woman. Adenomatoid tumours in the
      suprarenal glands are rare and are most often found incidentally. A definitive
      diagnosis is made on the basis of histology since imaging methods are non
      specific. Differential diagnoses comprise malignant vascular neoplasm or
      adenocarcinoma. Immunohistochemistry or electron microscopy allows uncomplicated
      distinction between these tumours. In general, it is recommended to obtain
      biopsies from suprarenal processes.

PMID- 19176158
TI  - [Bilateral suprapubic abscessses five years after incontinence surgery].
AB  - This report presents a case of vaginal erosion and bilateral suprabupic abscesses
      five years after insertion of an intravaginal slingplasty (IVS) midurethral
      incontinence sling in a 53-year-old female patient. Partial removal was
      insufficient. After complete removal, the patient achieved full recovery. As
      opposed to the macroporous types (e.g. tension-free vaginal tape), the
      microporous structure of the IVS-sling causes a higher rate of erosion and
      infection. Complete sling removal is important in case of IVS-complications. The
      monitoring of complications related to new medical devices is insufficient in
      Denmark.

PMID- 19176157
TI  - [In-hospital resuscitation with automated external defibrilliator].
AB  - Early defibrillation is a determinant of survival in cardiac arrest. We report a
      Danish case of successful in-hospital resuscitation using an automated external
      defibrillator (AED). This case illustrates important aspects of implementation of
      in-hospital use of an AED, i.e. location of the AED, education of the staff,
      systematic registration and data collection and technical aspects of AED use. If
      in-hospital AED implementation is carefully executed, its use may provide a safe
      and effective way of obtaining early defibrillation.

PMID- 19176159
TI  - [Lymphangioma of the oesophagus].
AB  - Lymphangiomas are benign tumours that rarely occur in the oesophagus. Only 14
      cases have been reported in the literature. This is a case of a 43-year-old woman
      with vague upper gastrointestinal discomfort. A sessile, 5-mm polyp was seen at
      gastroscopy. Lymphangioma was diagnosed by histology of the polypectomy specimen.
      Since no malign transformation has ever been reported, control after polypectomy
      was deemed unnecessary. Diagnostic and therapeutic considerations are briefly
      discussed.

PMID- 19176160
TI  - [Small bowel perforation following microsurgical diskectomy of lumbar disk
      prolapse].
AB  - Intraabdominal lesions after microsurgical discectomy are rare but potentially
      life threatening. We report a case of a 47-year-old male who developed abdominal
      pain after discectomy. An abdominal computer tomography demonstrated free air
      intraperitoneally, and a perforation of the ileum was found by laparotomy. A
      resection and primary anastomosis was performed. Patients who experience
      abdominal pain after discectomy should have an acute abdominal computer
      tomography performed to diagnose any intraabdominal lesions.

PMID- 19176161
TI  - [Carotinaemia in patient with excessive beta-carotene food-intake and
      dysregulated diabetes mellitus].
AB  - A case of carotinaemia in a patient with excessive beta-carotene food-intake,
      diabetes mellitus and physiological amenorrhea is reported. The patient developed
      yellow discolouration in the palms and the soles of her feet. Blood samples
      showed a significantly increased lever of serum beta-carotene, but normal
      vitamine A value and liver enzymes. The patient reported an excessive intake of
      carrots (approximately 1 kg per day). The status of physiological amenorrhoea and
      dysregulated diabetes mellitus may have deteriorated the yellow discolouration of
      the skin.

PMID- 19176162
TI  - [Rapidly progressing visual loss in idiopathic intracranial hypertension].
AB  - Idiopathic intracranial hypertension (IIH) is a condition of increased
      intracranial pressure of unknown aetiology. Slowly progressing visual defects
      secondary to papilloedema are well-known complications. Rapidly progressing
      visual loss is rare. A case of acute and rapidly progressing visual loss in
      idiopathic intracranial hypertension is presented. Rapid recognition and
      treatment of IIH is important, and may occasionally prompt acute surgical
      treatment.

PMID- 19176163
TI  - [Alcoholic ketoacidosis and lactic acidosis].
AB  - Alcoholic ketoacidosis (AKA) and alcoholic lactic acidosis (ALA) are metabolic
      disorders which occur in alcoholics after an episode of binge drinking and
      subsequent abrupt termination of alcohol and food consumption. Abdominal pain,
      nausea and vomiting trigger the biochemical changes resulting in metabolic
      acidosis with increased anion gap. Other symptoms are tachycardia, hypotension
      and tachypnea. Untreated AKA and ALA can cause sudden unexpected death. The
      following is an account of a patient who after hip surgery developed severe
      lactic acidosis and died.

PMID- 19176164
TI  - [Congenital transposition of the great arteries newly diagnosed in a 76-year-old
      woman].
AB  - A case of congenitally corrected transposition presenting for the first time with
      second-degree AV block in a 76-year-old woman is presented. This case
      demonstrates that congenitally corrected transposition can remain asymptomatic
      and undiagnosed, especially when no other cardiac defects are present.

PMID- 19176165
TI  - [Double cardiac arrest caused by amniotic fluid embolism during caesarean
      section].
AB  - Amniotic fluid embolism is a rare unpredictable complication of pregnancy with
      high maternal morbidity and mortality rates because of the risk of cardio
      respiratory collapse and/or disseminated intravascular coagulation (DIC). We here
      report a case of a patient who survived without any sequelae after two cardiac
      arrests and subsequent DIC due to amniotic fluid embolism during a caesarean
      section. Early consideration of the diagnosis after prompt resuscitation is
      needed to reduce morbidity and mortality.

PMID- 19176167
TI  - [Aggressive fibromatosis of the frontal sinus].
AB  - Aggressive fibromatosis (AF) is a benign tumour with expansive and locally
      invasive growth. It is very rarely seen in the head and neck area. We present a
      52-year-old female patient with AF localized to the left frontal sinus. The
      condition was initially mistaken for chronic sinusitis however computed
      tomography indicated tumour. A biopsy showed AF and the patient received surgical
      treatment. Symptoms, signs and treatment are discussed. It is concluded that AF
      in the sino-nasal tract is a rare, but potentially life threatening condition
      which might be mistaken for a simple sinusitis.

PMID- 19176166
TI  - [Chronic pulmonary alterations in children with long-lasting productive cough].
AB  - A productive (sounding) cough is always abnormal, and suppurative lung disease
      should be considered. A chronic suppurative cough may be associated with the
      destruction of the bronchial wall (bronchiectasis). The most commonly
      identifiable cause of suppurative cough is cystic fibrosis. This article, which
      is accompamied by an illustrative CT-scan, describes two paediatric cases of
      cystic fibrosis and primary ciliary dyskinesia and suggests appropriate avenues
      of clinical investigation, when chronic suppurative cough presents in children.

PMID- 19176168
TI  - [Red painful feet after visiting a swimming bath].
AB  - Idiopathic palmoplantar eccrine hidradenitis is characterised by painful
      erythematous plantar and/or palmar nodules and is triggered by exposure to wet
      and cold conditions. The course is benign and self-limiting with a tendency for
      recurrence. We describe two cases in otherwise healthy children after physical
      activity in a swimming bath. They were hospitalised for one and three days,
      respectively. Diagnostic considerations are briefly reviewed. Sufficient
      attention to the characteristic clinical appearance could prevent unnecessary
      diagnostic procedures and hospitalisation.

PMID- 19176169
TI  - [Compartment syndrome following adder bites].
AB  - Bites from the adder, Vipera Berus, can have serious clinical consequences due to
      systemic effects. Meanwhile, the local swelling calls for attention as well. Two
      cases of seven- and eleven-year-old boys are reported. The first patient was
      bitten in the 5th toe, the second in the thumb. Both developed fasciotomy
      requiring compartment syndrome of the lower and upper limb, respectively.
      Recognition of this most seldom complication of an adder bite is vital to save
      the limb. We recommend that the classical signs and symptoms of compartment
      syndrome serve as indication for surgery. However, compartment pressure
      measurement can be helpful in the assessment of children.

PMID- 19176170
TI  - [Resuscitation of severely hypothermic and multitraumatised female following long
      term cardiac arrest].
AB  - We describe the case of a patient who was severely hypothermic after 45 minutes
      of submersion. The patient received about 90 minutes of basic and advanced life
      support before being connected to extra corporal heart lung assistance (ECHLA).
      The core temperature was 28.9 degrees C, plasma potassium was 3.7 mmol/l. The
      patient stabilized and was discharged without significant sequelae after four
      weeks. This case report describes the importance of basic life support in the
      hypothermic patient and the use of ECHLA.

PMID- 19176171
TI  - [Endogenous Clostridium septicum panophthalmitis associated with gastrointestinal
      malignancy].
AB  - Endogenous panophthalmitis due to Clostridium septicum (C. septicum) is a rare,
      but life-threatening condition. There is a known association between infection
      and malignancy. Our patient presented with panophthalmitis - with visual loss,
      proptosis, raised intraocular pressure and air bubble in the anterior chamber. C.
      septicum was found in cultures of pus. He was treated with antibiotics and
      surgery, and recovered. Further investigations showed carcinoma of the colon.
      This case stresses the need for urgent treatment and subsequent investigation for
      occult malignancy.

PMID- 19176172
TI  - [Wartenberg's migrant sensory neuritis].
AB  - Two patients with progressive multifocal sensory symptoms and signs are
      described. The sensory disturbances were bilateral, and mainly arose in the
      territory of the radial nerves. Stretching or touching the wrist elicited
      electrical sensations in the fingers. The diagnosis of Wartenberg's migrant
      sensory neuritis (WMSN) was suggested. Nerve conduction studies confirmed the
      presence of peripheral nerve affection, and the electrophysiological
      abnormalities corresponded to the pattern and progression of clinical
      abnormalities.

PMID- 19176173
TI  - [Hereditary angioedema--diagnostic problems].
AB  - Hereditary angioedema (HAE) is a rare, but potentially life-threatening
      condition, clinically characterized by recurrent and self-limiting episodes of
      swelling which affect the skin, gastrointestinal tract and upper airways, and are
      caused by a lack of complement-C1-inhibitor (C1-INH). Within the past ten years,
      two Danish HAE patients have died from laryngeal oedema. We report two cases that
      illustrate symptoms and differential diagnostic problems posed by this disease,
      and the importance of an effective treatment strategy.

PMID- 19176174
TI  - [Neuromyelitis optica with atypical cerebral lesions demonstrated by magnetic
      resonance imaging in a 9-year old girl].
AB  - Neuromyelitis optica (NMO) is a rare inflammatory disorder characterised by optic
      neuritis and transverse myelitis. We report a severe pediatric case presenting
      with impaired vision, tetraparesis, bladder retention and lower extremity pain.
      Magnetic resonance imaging demonstrated longitudinally extensive lesions of the
      spinal chord and atypical lesions in both cerebral hemispheres. Cerebrospinal
      fluid was pleocytotic. Symptoms responded well to intravenous immunoglobulin G
      and high-dose methyl prednisolone therapy.

PMID- 19176175
TI  - [Incomplete Brown-Sequard syndrome with Horner syndrome due to plastic foreign
      body in cervical medulla].
AB  - A case presentation and discussion of a 32-year old male presenting an incomplete
      Brown-Sequard syndrome with Horner syndrome due to a plastic foreign body in the
      cervical medulla.

PMID- 19176176
TI  - [Streptococcus pyogenes infection with tonsillar focus as possible cause of
      septic shock].
AB  - Streptococcus pyogenes (SP) is a common bacterial pathogen. For the past two
      decades, several studies have reported an increase in the severity and the
      incidence of SP infections. CASE: a 60-year-old female admitted to the hospital
      with tonsillitis acuta verified by strep-A test was initially treated with V
      penicillin, but developed septic shock and disseminated intravascular coagulation
      (DIC), and treatment was changed to cefuroxime and clindamycin. She recovered
      fully. This case combined with other studies illustrates that SP infections have
      become more severe. Clindamycin should be added to penicillin for the treatment
      of invasive SP infections.

PMID- 19176177
TI  - [Multi-facetted clinical presentation of thrombotic thrombocytopenic purpura].
AB  - Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathic
      disease. TTP is due to reduced activity of the von Willebrand factor which
      cleaves ADAMTS13. The disease is characterized by thrombocytopenia (<20
      billion/l) intravascular Coombs-negative haemolysis and schistocytes in blood
      smears. Determination of the ADAMTS13-activity is now becoming available as a
      routine analysis. We present two cases that illustrate the multi-facetted
      clinical presentation under which TTP occurs. The importance of access to
      ADAMTS13 measurements is stressed.

PMID- 19176178
TI  - Plantar pressure pain thresholds and touch sensitivity in rheumatoid arthritis.
AB  - BACKGROUND: In-shoe pressure redistribution to provide relief of forefoot pain in
      rheumatoid arthritis (RA) is based on assumed links between pressure and pain.
      However, little is known about the size of the pressure change required to reduce
      pain or the capacity of other plantar regions to bear increased pressure. Our
      primary aim was to quantify the plantar pressure pain threshold (PPT) in RA and
      compare it to age- and gender-matched control participants. MATERIALS AND
      METHODS: This controlled trial involved 10 RA participants and 10 age- and gender
      matched control subjects. PPT, measured using a force gauge, and touch
      sensitivity, measured via Semmes-Weinstein monofilaments, were tested in 19
      plantar regions. RESULTS: RA plantar PPTs were significantly reduced in eight
      foot regions (p < 0.05) and were more uniform across the plantar surface. Touch
      sensitivity was not different between groups. Plantar PPT was significantly
      related to age (p < 0.05) and to touch sensitivity (p < 0.05) in multiple foot
      regions of the control group but not in RA. PPT was significantly correlated with
      disease duration (p < 0.05). CONCLUSION: Plantar PPTs in RA were 60% to 80% of
      the control group and may be helpful in predicting the amount of pressure
      reduction needed to relieve pain. This study provides further evidence that RA
      disturbs normal pain sensory mechanisms.

PMID- 19176179
TI  - Fusion versus excision of the symptomatic Type II accessory navicular: a
      prospective study.
AB  - BACKGROUND: Patients with symptomatic Type II accessory naviculars that fail
      nonoperative measures may be treated with excision, percutaneous drilling, a
      modified Kidner procedure, or a fourth option, arthrodesis of the accessory
      ossicle to the navicular body. There is little information in the literature on
      the relative merits of arthrodesis. MATERIALS AND METHODS: A prospective
      evaluation of 20 patients undergoing surgical intervention for symptomatic Type
      II accessory naviculars was performed. The decision to perform either an
      arthrodesis (10 feet) or a modified Kidner (10 feet) was made intraoperatively
      based on the size of the accessory ossicle. Outcomes were measured using pre- and
      postoperative American Orthopaedic Foot and Ankle Society (AOFAS) Midfoot scores,
      plain radiographs, and chart reviews. RESULTS: At an average followup of 35
      months, the mean AOFAS score for the arthrodesis group improved from 50 to 93
      points. There were two non-unions (20%) and one patient complained of painful
      hardware. At an average followup of 48 months, the mean AOFAS score for the
      modified Kidner group improved from 52 to 80 points. However, in this group,
      three of ten patients (30%) had persistent midfoot pain and radiographic evidence
      of progressive loss of the longitudinal arch. CONCLUSION: Although the methods do
      not represent a randomized comparison of treatments for the same condition, the
      results suggest that arthrodesis may be a reasonable treatment option in selected
      cases of patients with symptomatic recalcitrant Type II accessory naviculars that
      are large enough to accept small fragment screws.

PMID- 19176180
TI  - Long-term results of Mitchell's procedure for hallux valgus deformity: a 5- to 20
      year followup in 204 cases.
AB  - BACKGROUND: There are limited studies on the long term outcome of Mitchell's
      osteotomy for hallux valgus deformity. We present the long term results of 204
      cases. MATERIALS AND METHODS: Postoperative clinical and radiological evaluation
      with a mean follow up of 12.9 years was performed on patients with preoperative
      hallux valgus angles (HVA) of up to 50 degrees and intermetatarsal angles (IMA)
      of up to 20 degrees. Two crossed Kirschner wires were used to fix the capital
      fragment; lateral soft tissue release performed when deemed necessary.
      Comparisons were made between the pre- and postoperative measurements using a
      Mann-Whitney U-test. Statistical significance was defined at p < 0.05. RESULTS:
      The mean AOFAS score improved from 49.6 to 87.9 points (p = 0.004). There was
      significant improvement in the HVA and IMA, 33.8 degrees versus 16.1 degrees (p =
      0.002) and 15.2 degrees versus 8.2 degrees (p = 0.004), respectively. Fifty-seven
      cases (27.9%) had preoperative HVA greater than 40 degrees but only 16 required
      lateral soft tissue release with no significant difference in the postoperative
      HVA (21.3 versus 20.8, p = 0.08). There was a significant change in lateral
      metatarsalgia and symptomatic callosities (18.3% versus 11.8%, p = 0.023). In
      97.6% of cases the patients were satisfied with the overall result. Revision
      surgery was performed in five cases (2.5%). CONCLUSION: Mitchell's osteotomy was
      a reliable technique with successful outcome and low complication rate when
      performed with Kirschner wire fixation and lateral soft tissue release when
      appropriate. It may also be successfully performed with hallux valgus angles
      greater than 40 degrees.

PMID- 19176181
TI  - Single medial approach to modified double arthrodesis in rigid flatfoot with
      lateral deficient skin.
AB  - BACKGROUND: Triple arthrodesis through a two-incision approach is the traditional
      surgical treatment of fixed flatfoot in adults. However, since it limits motion
      and forces the remaining joints to absorb more load, long-term studies report
      diminishing results over time from symptomatic breakdown of adjacent joints. In
      addition, wound-healing problems have been reported in up one-third of patients
      undergoing a major flatfoot reconstruction which are more commonly associated
      with the anterolateral approaches. Therefore, since 2003, we have been interested
      in selective arthrodesis of the subtalar and talonavicular joints sparing the
      uninvolved calcaneocuboid joint and the lateral skin. MATERIALS AND METHOD: We
      have performed this procedure in 11 patients (14 feet) who had deficient lateral
      skin and a fixed hindfoot valgus deformity where adequate correction may have led
      to lateral wound complication. They were followed in a prospective fashion and
      assessed at a minimum of 6 months followup. RESULTS: Wound healing occurred
      without any complications in all cases. Evaluation was performed at an average of
      21.5 (range, 6 to 50) months. Significant radiographic improvements were observed
      on each measurement: anteroposterior talonavicular coverage angle improved from
      38.5 degrees to 7 degrees, lateral talo-first metatarsal angle improved from 21
      degrees to 0 degrees, hindfoot frontal alignment angle improved from 18 degrees
      to 7.5 degrees. All patients had an asymptomatic calcaneocuboid joint.
      CONCLUSION: Arthrodesis of the subtalar and talonavicular joints through a medial
      approach combined with peroneal lengthening is a reliable procedure for the
      treatment of rigid flatfoot with deficient lateral skin without calcaneocuboid
      joint degeneration.

PMID- 19176182
TI  - Comparison of 4.5- and 5.5-mm cannulated stainless steel screws for fifth
      metatarsal Jones fracture fixation.
AB  - BACKGROUND: Complications including delayed and nonunions, and extensive time
      nonweightbearing with conservative treatment of fifth metatarsal Jones fractures,
      have led authors to recommend surgical fixation for this fracture in athletes who
      wish to return to activity quickly. The optimal surgical procedure, however, has
      not been determined. The purpose of this study was to evaluate the effectiveness
      of 5.5-mm cannulated screw fixation for fifth metatarsal stress fractures in
      athletes and compare them to an earlier cohort treated with a 4.5-mm screw.
      MATERIALS AND METHODS: Twenty athletes were treated surgically with a 5.5-mm
      cannulated screw and postoperatively wore a removable walking boot, applied cold
      compression, initiated immediate range of motion, and used crutches for 1 week.
      Fractures were evaluated for clinical and radiographic healing. These findings
      were compared to a group that used 4.5-mm screws. RESULTS: Average radiographic
      healing was 96.7% and all fractures healed clinically. Athletes returned to
      sports in an average of 9.3 weeks. There were three re-injuries that were treated
      with 2 weeks in a walking boot. No patients have required screw removal or have
      experienced pain at the hardware site, besides the three re-injuries. When
      compared to the earlier study, no differences were found. However, there were no
      re-fractures in the 4.5-mm study, but there were three bent screws. CONCLUSION:
      The current study demonstrates the clinical effectiveness of the 5.5-mm screw.
      However, with the numbers available, we were unable to demonstrate significant
      improvement over the 4.5-mm screw and thus cannot conclude that a larger screw is
      more effective.

PMID- 19176183
TI  - Results of distal metatarsal osteotomy using absorbable pin fixation.
AB  - BACKGROUND: Metatarsalgia with plantar hyperkeratosis can be a difficult problem
      to treat. Many different techniques have been reported with the Weil osteotomy
      very popular currently. Despite good results complications include
      metatarsophalangeal stiffness, hyperextension of the toe, prehensile deficit and
      a reduction in strength. We evaluated our results with a distal diaphyseal
      osteotomy. MATERIALS AND METHODS: From 1999 to 2005, we performed 66 distal
      midshaft subtraction osteotomies in 62 patients suffering from metatarsal
      overload without metatarsophalangeal subluxation. Fixation was obtained with an
      absorbable pin. Some patients underwent simultaneous corrective surgery for
      hallux valgus, hallux rigidus or lesser toe deformities. There was an average of
      18 months followup. RESULTS: The mean preoperative Maryland score was 52; the
      mean postoperative score was 86. Seventy-two percent of the patients were very
      satisfied and 28% felt their condition improved with only occasional pain (VAS 2
      to 4). The only complications reported was a loss of correction due to breakage
      of the pins in three patients (two sustained trauma and the third began walking
      prematurely without a postoperative shoe). CONCLUSION: The good clinical results
      obtained and the low incidence of complications have encouraged us to use this
      technique to treat symptomatic metatarsal overload. Surgical accuracy, adherence
      to the postoperative regimen and, where necessary, adequate correction of the
      first ray were important factors for success.

PMID- 19176184
TI  - Radiographic evaluation for AVN following distal metatarsal Stoffella bunion
      osteotomy.
AB  - BACKGROUND: Avascular necrosis of the metatarsal head, delayed bone healing and
      nonunion are complications that may occur after distal first metatarsal
      osteotomies. Intraoperative damage to the extraosseous blood supply, the location
      of the osteotomy and postoperative vasospasm have been cited as possible causes
      of such changes. We evaluated Stoffella's subcapital osteotomies which were
      performed at our department for the correction of moderate to severe hallux
      valgus deformities. MATERIALS AND METHODS: Standardized radiographs of 300 feet,
      taken 6weeks, 3 months, and 6 months postoperatively and at the final followup
      were examined with regard to postoperative AVN or signs of delayed bone healing.
      Of 228 patients, 202 were women and 26 were men. The patients' mean age was 49
      years, and the mean followup was 12 months. RESULTS: In 278 cases the radiographs
      revealed an unremarkable first metatarsal head. Seventeen cases showed diffuse or
      localized osteopenia or small cysts in the subchondral bone. These changes fully
      resolved on subsequent radiographs. The X-rays of two patients revealed
      progressive narrowing of the joint space, irregular contours on the surface of
      the joint and an abnormal bone structure. The patients subsequently developed a
      characteristic picture of avascular necrosis, in one case combined with nonunion.
      Three patients had delayed bone healing, but ultimately healed successfully.
      CONCLUSION: Ischemic changes in bone are known to occur after distal first
      metatarsal osteotomies. There is a very low incidence of postoperative perfusion
      problems after Stoffella;s technique, even with lateral soft tissue release.

PMID- 19176185
TI  - Cadaveric simulation of a pes cavus foot.
AB  - BACKGROUND: The pes cavus deformity has been well described in the literature;
      relative bony positions have been determined and specific muscle imbalances have
      been summarized. However, we are unaware of a cadaveric model that has been used
      to generate this foot pathology. The purpose of this study was to create such a
      model for future work on surgical and conservative treatment simulation.
      MATERIALS AND METHODS: We used a custom designed, pneumatically actuated loading
      frame to apply forces to otherwise normal cadaveric feet while measuring bony
      motion as well as force beneath the foot. The dorsal tarsometatarsal and the
      dorsal intercuneiform ligaments were attenuated and three muscle imbalances, each
      similar to imbalances believed to cause the pes cavus deformity, were applied
      while bony motion and plantar forces were measured. RESULTS: Only one of the
      muscle imbalances (overpull of the Achilles tendon, tibialis anterior, tibialis
      posterior, flexor hallucis longus and flexor digitorum longus) was successful at
      consistently generating the changes seen in pes cavus feet. This imbalance led to
      statistically significant changes including hindfoot inversion, talar
      dorsiflexion, medial midfoot plantar flexion and inversion, forefoot plantar
      flexion and adduction and an increase in force on the lateral mid- and forefoot.
      CONCLUSION: We have created a cadaveric model that approximates the general
      changes of the pes cavus deformity compared to normal feet. These changes mirror
      the general patterns of deformity produced by several disease mechanisms.
      CLINICAL RELEVANCE: Future work will entail increasing the severity of the model
      and exploring various pes cavus treatment strategies.

PMID- 19176186
TI  - Effects of rigid and dynamic ankle-foot orthoses on normal gait.
AB  - BACKGROUND: As shown through posturographic data, wearing an ankle-foot orthosis
      (AFO) causes a backward shift in healthy subjects of the mean position of the
      center of pressure under the limb wearing it, and difficulty in controlling these
      displacements. This study evaluated whether this particular positioning
      influenced gait independent of a neurological disorder. MATERIALS AND METHODS:
      Two AFO models, with different mechanical concepts (a rigid-AFO (R-AFO) and
      dynamic-AFO (D-AFO)), were worn by 11 healthy subjects required to walk on a 12-m
      electronic mat. Velocity, step time and step length were assessed for each of the
      five conditions where subjects walked barefoot, and wearing R-AFO or D-AFO
      (without and with slight and greater stiffness at the elastic band). Spatial and
      temporal characteristics of each support were also analyzed. RESULTS: Although
      wearing R-AFO disturbed velocity, step length and time with an asymmetry between
      sides, wearing the D-AFO only affected a support characteristic (midline length:
      length between the pivot points of the two dimensional sensor structure of heel
      and toe area). No effect was seen when modifying the stiffness of the D-AFO
      model. CONCLUSION: Even though the posturographic data might partly explain this
      behavior, wearing an orthosis caused different effects on normal gait parameters.
      CLINICAL RELEVANCE: These features should be useful when prescribing an ankle
      foot orthosis by differentiating what alterations are due to the orthosis and
      which are due to the gait disorder.

PMID- 19176187
TI  - Ethnic radiographic foot differences.
AB  - BACKGROUND: The prevalence of foot and ankle conditions varies among different
      ethnic groups. It is not known if this difference is due to any distinctive
      skeletal morphological characteristics of the foot. The purpose of this study was
      to determine if ethnic differences exist in the morphometric measurements on
      radiographs of the weightbearing foot. MATERIALS AND METHODS: A morphometric
      study of weightbearing radiographs of feet was performed prospectively.
      Radiographic parameters were measured on digital monitors using digital tools.
      These were the hallux valgus angle (HVA), intermetatarsal angle (IMA),
      talonavicular angle (TNA), talonavicular coverage angle (TNCovA), metatarsal span
      (MS) on anteroposterior (AP) radiographs and talo-first metatarsal angle (T
      1(st)MTA), calcaneal pitch (CP), and lateral talocalcaneal angle (LTCA) on
      lateral radiographs. RESULTS: A total of 237 feet in 126 patients (45 African
      Americans, 59 Caucasians, and 22 Hispanics) were studied. Statistically
      significant differences were found in the CP, LTCA, and MS. African Americans
      have significantly lower CP than Caucasians (p < 0.0001). African Americans have
      significantly lower CP than Hispanics (p < 0.0016). Caucasians have significantly
      higher TCA than African Americans (p < 0.0004). Males have a larger MS than
      females (p < 0.0001). CONCLUSION: There are differences in the radiographic
      morphology of feet among different ethnic groups. A larger prospective community
      based study of morphological differences is needed for better understanding of
      the genetic and environmental factors influencing the prevalence of foot and
      ankle conditions. CLINICAL RELEVANCE: The clinical relevance between having a
      lower CP angle and a higher incidence of flat feet in African Americans warrants
      further investigation. It is not known if there is a relationship between
      posterior tibialis insufficiency and low CP.

PMID- 19176188
TI  - Augmented subatmospheric wound dressings (SAWDA): technique tip.

PMID- 19176189
TI  - Repair of the achilles tendon sleeve avulsion: a transcalcaneal suture technique.

PMID- 19176190
TI  - Technical tip: fixation of medial malleolar fractures using a suture anchor.

PMID- 19176191
TI  - Arthroscopic-assisted fluoroscopic navigation for retrograde drilling of a talar
      osteochondral lesion.

PMID- 19176192
TI  - Adjuvant arthroscopy for ankle tuberculosis: a report of two cases.

PMID- 19176193
TI  - Staged total ankle arthroplasty following Ilizarov correction for osteoarthritic
      ankles with complex deformities: a report of three cases.

PMID- 19176194
TI  - Current concept review: perioperative soft tissue management for foot and ankle
      fractures.

PMID- 19176195
TI  - FootForum: the crisis in academic medicine.

PMID- 19176196
TI  - Acute myeloid leukemia.

PMID- 19176197
TI  - Strategy for incorporating molecular and cytogenetic markers into acute myeloid
      leukemia therapy.
AB  - Acute myeloid leukemia is a heterogeneous disease. Standard treatments may be
      applied to biologically distinct subgroups, resulting in different treatment
      outcomes. The concept of risk-adapted therapy allows for recognition of this
      biologic diversity by incorporating key biologic features, such as cytogenetic
      and molecular markers, when formulating treatment regimens and investigating
      emerging targeted therapies based on disease characteristics.

PMID- 19176198
TI  - Optimizing therapy for acute myeloid leukemia.
AB  - The 10-year overall survival for younger patients with newly diagnosed acute
      myeloid leukemia has improved threefold in the past 2 decades. This improvement
      has occurred in large part because of advances in supportive care and efforts to
      optimize standard induction and consolidation therapies applied in a stratified
      approach based on predictors of individual patient risk. Innovations in
      diagnostic technologies have broadened the understanding of key prognostic
      factors, including cytogenetic and molecular status, which define the extensive
      interpatient heterogeneity of this clonal disease. Despite this progress, only
      approximately 25% of patients who experience a complete remission with cytotoxic
      chemotherapy (50%-70% of patients with newly diagnosed disease) remain disease
      free. Efforts to develop novel agents are actively ongoing, particularly for
      older patients (age > or = 60), and targeted therapies, for specific subsets of
      patients are being based on a better understanding of the biology of the disease.

PMID- 19176199
TI  - Therapy for older AML patients: the role of novel agents and allogeneic stem cell
      transplant.
AB  - The development of novel therapeutics in acute myeloid leukemia (AML) is driven
      by the need to improve efficacy and reduce toxicity. Clearly, elderly patients
      with AML represent a highly heterogeneous group, based on a wide array of disease
      and patient-specific characteristics. Therefore, novel treatment strategies
      aimed at overcoming specific biologic modifiers of disease resistance will be
      paramount to successful therapy for some, whereas in others, the ability to
      administer a low-toxicity regimen on a chronic basis to achieve disease control
      may prove beneficial, perhaps even in the absence of complete responses. In
      addition, identifying genomic and proteomic expression patterns using an
      individual's unique neoplastic clone will likely optimize the ability to predict
      responders to novel therapies and identify new and relevant therapeutic targets.
      The development of reduced-intensity preparative regimens for allogeneic
      transplants has allowed physicians and patients to explore the option of long
      term disease control. The risk-benefit ratio for this procedure will depend on
      the disease state, patient performance status, and comorbidities. However,
      current results underscore that age alone should no longer be a contraindication
      for allogeneic transplant with curative intent in these patients, and long-term
      disease control with good quality of life is possible and can be expected. Future
      trials combining the novel therapies described in this article and novel
      transplant technologies should allow more elderly patients with AML or
      myelodysplastic syndromes to experience long and productive lives.

PMID- 19176200
TI  - Occult primary.

PMID- 19176201
TI  - Therapy of adenocarcinoma of unknown primary: are we making progress?
AB  - Therapy for patients with unknown primary carcinoma is evolving and requires a
      detailed understanding of the various clinicopathologic subsets with more
      favorable prognoses. For the remainder, and most patients with unfavorable
      prognoses, data on current empiric chemotherapy with the newer drugs seems to
      show improved overall survival compared with older historical data, including
      comparisons with large retrospective series and prospective phase II trial
      results. Several recent clinical trials have recently documented long-term
      survival for a minority of patients. The survival of patients with several
      metastatic adenocarcinomas of known primary sites, including colon/rectum, lung,
      and pancreas, has been improved by the administration of chemotherapy alone or
      combined with biologic targeted drugs (bevacizumab, erlotinib). Approximately 60%
      of the patients with unknown primary adenocarcinoma have clinically occult
      primary sites of colon/rectum, lung, and pancreas. Many of these patients will
      also benefit from therapeutic regimens now proven to be useful for patients with
      these known primary sites. All available data make a convincing argument that
      progress is being made for the commonly seen patients with adenocarcinoma of
      unknown primary site, and is likely to continue as understanding of these and
      other neoplasms further evolves.

PMID- 19176202
TI  - Evaluation and management of the unknown primary carcinoma of the head and neck.
AB  - Squamous cell carcinoma of unknown primary origin in the head and neck is
      encountered as a recurring clinical problem in head and neck cancer clinics,
      affecting 3% to 25% of patients. This article describes the clinical
      presentation, appropriate evaluation, and treatment strategies for this important
      subgroup. Treatment--best carried out with multidisciplinary teams of specialists
      experienced in the care of head and neck cancer patients--is curative for most of
      these patients.

PMID- 19176203
TI  - Bladder cancer.

PMID- 19176204
TI  - Integrating perioperative chemotherapy into the treatment of muscle-invasive
      bladder cancer: strategy versus reality.
AB  - Since the initial report in 2003 of the Intergroup-0080 trial confirming benefit
      of combined neoadjuvant M-VAC (methotrexate, vinblastine, adriablastine, and
      cisplatin) chemotherapy and cystectomy in the treatment of muscle-invasive
      bladder cancer, debate has continued in the literature as to the relative
      risk/benefits of integrating perioperative chemotherapy into the care of
      patients, especially in those with organ-confined, muscle-invasive, node-negative
      disease in whom the benefit may be less. Because of the inaccuracies of clinical
      staging, the potential morbidity related to M-VAC chemotherapy, a 70% cure rate
      in pT2No disease with surgery alone, and only a modest (5%) improvement in
      absolute overall survival with combined therapy, many favor limiting chemotherapy
      to patients with a pathologic stage of pT3 or greater or node-positive disease.
      This philosophy was also reflected in the 2008 National Comprehensive Cancer
      Network Clinical Practice Guidelines in Oncology: Bladder Cancer, in which
      neoadjuvant chemotherapy for clinical T2 disease versus adjuvant therapy based on
      pathologic risks is only "considered." Additionally, a recent study looking at
      the perioperative integration of chemotherapy for stage III bladder cancer in the
      United States using the National Cancer Data Base showed that only 11.6% of
      patients underwent any perioperative chemotherapy, with most in the adjuvant
      setting. These findings indicate that despite randomized trial data showing
      survival benefit for perioperative chemotherapy, and the current guidelines for
      therapy supporting those findings, chemotherapy is not being integrated well into
      the care of patients with muscle-invasive bladder cancer, even in those who,
      experts agree, have the most potential for benefit.

PMID- 19176205
TI  - Carcinoma in situ of the urinary bladder: review of clinicopathologic
      characteristics with an emphasis on aspects related to molecular diagnostic
      techniques and prognosis.
AB  - Carcinoma in situ (CIS) of the urinary bladder is defined as a flat lesion
      comprising of cytologically malignant cells which may involve either full or
      partial thickness of the urothelium. De novo CIS constitutes less than 3% of all
      urothelial neoplasms; however, CIS detected concurrently or secondarily during
      follow-up of urothelial carcinoma constitutes 45% and 90%, respectively, of
      bladder cancer. CIS is noted predominantly in male smokers in the sixth or
      seventh decade. Patients may present with dysuria, nocturia, and urinary
      frequency and urgency with microscopic hematuria. Cystoscopic findings may range
      from unremarkable to erythema or edema. Urine cytology is an important diagnostic
      tool. Cellular anaplasia, loss of polarity, discohesion, nuclear enlargement,
      hyperchromasia, pleomorphism, and atypical mitoses are the histopathologic
      hallmarks of CIS. Extensive denudation of the urothelium, monomorphic appearance
      of the neoplastic cells, inflammatory atypia, radiation induced nuclear smudging,
      multinucleation, and pagetoid spread of CIS may cause diagnostic difficulties.
      Together with clinical and morphologic correlation, immunostaining with CK 20,
      p53 (full thickness), and CD44 (absence of staining) may help accurately diagnose
      CIS. Fluorescent in situ hybridization analysis of voided urine for amplification
      of chromosomes 3, 7, and 17 and deletion of 9p has high sensitivity and
      specificity for diagnosing CIS in surveillance cases. Several other molecular
      markers, such as NMP 22 and BTA, are under evaluation or used variably in
      clinical pathology. Intravesical bacillus Calmette-Guerin (BCG) instillation is
      considered the preferred treatment, with radical cystectomy being offered to
      refractory cases. Chemotherapy, alpha-interferon, and photodynamic therapy are
      other modalities that can be considered in BCG-refractory cases. Multifocality,
      involvement of prostatic urethra, and response to BCG remain the most important
      prognostic factors, although newer molecular markers are being evaluated for this
      entity. Patient outcome varies based on whether it is de novo development or
      diagnosed secondary to prior or concomitant papillary bladder cancer. From a
      clinical perspective, the principal determinants of outcome are extent of
      disease, involvement of prostatic urethra, response to therapy, and time to
      recurrence.

PMID- 19176206
TI  - Limitations of lymph node counts as a measure of therapy.
AB  - For several cancers, the number of lymph nodes removed during surgery is
      associated with survival. Observational studies supporting this association have
      prompted considerable debate regarding the extent of lymphadenectomy, and in some
      dieases, absolute lymph node counts have been suggested as a measure of the
      quality of cancer care. However, for most cancers, lymph node counts may not
      directly influence survival in a causal manner. In fact, several randomized
      clinical trials addressing the question in lung, gastric, and pancreatic cancers
      have not shown more extensive lymph node dissections to be linked with improved
      survival. Despite this negative evidence, however, lymph node counts have
      remained a target process in quality initiatives. Misinterpretation of the
      evidence may be driving some of the pressure to broadly implement more extended
      lymph node dissections. As a process for more accurate disease staging and as a
      potential marker for the completeness of surgery, lymph node counts are likely
      linked to quality, at least indirectly. However, a causal association between
      lymph node counts (and extented lymphadenectomy) and survival is tenuous and has
      not been supported by high-level evidence.

PMID- 19176207
TI  - Myeloid growth factors.

PMID- 19176208
TI  - The role of myeloid growth factors in acute leukemia.
AB  - Myeloid growth factors granulocyte-colony stimulating and granulocyte macrophage
      colony-stimulating factors have been extensively studied in acute leukemias.
      Whether administered before, during, or after chemotherapy for acute myeloid
      leukemia and acute lymphoblastic leukemia, these agents reduce the duration of
      neutropenia and seem to be safe and well tolerated. Despite consistently showing
      a shorter duration of neutropenia, multiple, prospective, randomized trials have
      documented only modest benefits in terms of reduction in the incidence and
      severity of infections, without substantial gains or impact in complete
      remission, overall survival, and disease-free survival rates. Growth factors have
      also been used to recruit quiescent leukemia cells into the S-phase of the cell
      cycle to increase their susceptibility to chemotherapy with the goal to reduce
      relapse and resistance. Randomized trials evaluating this priming strategy have
      consistently shown improvement in disease- or event-free survival in the
      intermediate-risk group of patients with acute myeloid leukemia, but no overall
      survival benefit. This article focuses on the clinical experience with these
      agents as adjuncts to the treatment of acute leukemias.

PMID- 19176209
TI  - Neutrophil biology and the next generation of myeloid growth factors.
AB  - Neutrophils are the body's critical phagocytic cells for defense against
      bacterial and fungal infections; bone marrow must produce approximately 10 x
      10(9) neutrophils/kg/d to maintain normal blood neutrophil counts. Production of
      neutrophils depends on myeloid growth factors, particularly granulocyte colony
      stimulating factor (G-CSF). After the original phase of development, researchers
      modified these growth factors to increase their size and delay renal clearance,
      increase their biologic potency, and create unique molecules for business
      purposes. Pegylated G-CSF is a successful product of these efforts. Researchers
      have also tried to identify small molecules to serve as oral agents that mimic
      the parent molecules, but these programs have been less successful. In 2006, the
      European Medicines Agency established guidelines for the introduction of new
      biologic medicinal products claimed to be similar to reference products that had
      previously been granted marketing authorization in the European community, called
      bio-similars. Globally, new and copied versions of G-CSF and other myeloid growth
      factors are now appearing. Some properties of the myeloid growth factors are
      similar to other agents, offering opportunities for the development of
      alternative drugs and treatments. For example, recent research shows that
      hematopoietic progenitor cells can be mobilized with a chemokine receptor
      antagonist, chemotherapy, G-CSF, and granulocyte macrophage colony-stimulating
      factor. Advances in neutrophil biology coupled with better understanding and
      development of myeloid growth factors offer great promise for improving the care
      of patients with cancer and many other disorders.

PMID- 19176210
TI  - Impact of chemotherapy dose intensity on cancer patient outcomes.
AB  - Chemotherapy dose intensity represents unit dose of chemotherapy administered per
      unit time. Dose intensity can be increased or decreased through altering dose
      administered, time interval of administration, or both. Evidence supporting the
      importance of delivered chemotherapy dose intensity on clinical outcomes in
      patients with potentially curable malignancies comes from in vitro studies of
      cancer cell lines and abundant in vivo preclinical studies, in addition to
      retrospective and prospective clinical trials in both advanced and early-stage
      disease settings. Myelosuppression continues to represent the major dose-limiting
      toxicity of cancer chemotherapy, resulting in considerable morbidity and
      mortality along with frequent reductions in chemotherapy dose intensity, which
      may compromise disease control and survival. Several retrospective and
      prospective randomized trials have shown that reductions in the chemotherapy dose
      intensity established in efficacy studies may compromise long-term disease
      control and survival. Despite compelling data, surveys in the United States and
      elsewhere have reported that dose reductions and delays frequently occur in
      clinical practice, even in the potentially curative setting. Alternatively, an
      increase in dose intensity above standard may be achieved through either
      increasing the dose of individual agents (dose escalation) or compressing or
      shortening the treatment interval (dose-dense). In early studies, dose-dense
      schedules showed an increase in survival, whereas the benefit of dose escalation
      studies has been less consistent and may be accompanied by other dose-limiting
      toxicities. This article focuses on the rationale for delivering full
      chemotherapy dose intensity, the apparent reasons for failing to deliver
      treatment, and available strategies for sustaining full chemotherapy dose
      intensity when indicated. The delivery of full chemotherapy dose intensity in
      patients with potentially curable malignancies should be considered a quality of
      care indicator in clinical oncology.

PMID- 19176214
TI  - Increased basement membrane thickness, pericyte ghosts, and loss of retinal
      thickness and cells in dopamine beta hydroxylase knockout mice.
AB  - Diabetes can cause damage to sympathetic nerves, and we have previously shown
      that experimental sympathectomy can produce capillary abnormalities in the retina
      similar to those seen in early diabetes. We postulate that the diabetes-induced
      loss of the sympathetic system, and at least in part the sympathetic
      neurotransmitter norepinephrine (NE), contributes to the development of retinal
      vascular and neural abnormalities in diabetes. Thus, we predict that non-diabetic
      animals that lack NE will develop microvascular and neural changes that are
      similar to those that are characteristic of diabetic retinopathy. To test this,
      retinas from non-diabetic dopamine beta hydroxylase (Dbh, Dbh(-/-)) knockout mice
      and their littermate controls were assessed for diabetic-like capillary and
      neural changes at 5 months of age. Genetic deletion of Dbh resulted in a
      significant decrease in retinal thickness and number of cells in the retinal
      ganglion cell layer (central retinal region). In addition, the number of pericyte
      ghosts and the basement membrane of retinal capillaries were significantly
      increased in the Dbh(-/-) mice. These results provide evidence that loss of
      sympathetic neurotransmission may contribute to the microvascular and neural
      changes of diabetic retinopathy. Restoration of sympathetic neurotransmission may
      be a new target for therapeutic intervention to inhibit the early phases of
      diabetic retinopathy.

PMID- 19176215
TI  - Retinal vascular repair and neovascularization are not dependent on CX3CR1
      signaling in a model of ischemic retinopathy.
AB  - Proliferative retinal neovascularization occurring in response to ischemia is a
      common mechanism underlying many retinal diseases. In recent studies, retinal
      microglia have been shown to influence pathological neovascularization, likely
      through an exchange of cellular signals with associated vascular elements. CX3CR1
      is a chemokine receptor located specifically on microglia; its ligand, CX3CL1
      (also known as fractalkine or neurotactin) displays pro-angiogenic activity both
      in in vivo and in vitro. Discovering the regulatory role, if any, that CX3CR1
      signaling may have in ischemic retinopathy will shed light on the molecular
      nature of microglial-vascular interactions and clarify potential targets for
      future therapy. In this study, we examined this question by inducing and
      comparing ischemic vascular changes in transgenic mice in which CX3CR1 signaling
      is either preserved or ablated. Using a well-known oxygen-induced retinopathy
      (OIR) model, we induced ischemic retinopathy in transgenic mice in which the gene
      for CX3CR1 has been replaced by green fluorescent protein (GFP) and their wild
      type controls. CX3CR1(+/+), CX3CR1(+/GFP), and CX3CR1(GFP/GFP) transgenic mice
      were exposed to 75% oxygen for 5 days starting from postnatal day (P) 7, and then
      transferred back to room air. At P12 and P17, the extents of vascular repair and
      neovascularization, and associated changes in retinal microglia distribution,
      were quantified and compared between mice of different genotypes. Neuronal loss
      in the retina following ischemia was also evaluated in paraffin sections. Our
      results show that: (1) CX3CR1 signaling is not required for normal vascular,
      microglial, and neuronal development in the retina in the first postnatal week,
      (2) the processes of retinal vascular repair and neovascularization following
      ischemia occur similarly with and without CX3CR1 signaling, (3) microglia
      redistribution in the retina and their association with vascular elements
      occurring concurrently is independent of CX3CR1, and (4) CX3CR1 does not
      influence the extent of neuronal cell loss in the retina following ischemia.
      Taken together, our findings indicate that the regulatory signals exchanged
      between microglia and vascular elements in the ischemic retinopathy animal model
      are unlikely to involve CX3CR1. These results have implications on therapeutic
      approaches to, pathological neovascularization involving the modulation of
      chemokine signaling in general, and the regulation of CX3CR1 signaling
      specifically.

PMID- 19176216
TI  - Infant limbus: an immunohistological study.
AB  - All published literature to date has identified the human corneo-scleral limbus
      as the site within which stem cells of the ocular surface reside. Recently we
      described a unique anatomical structure at the limbus, termed the Limbal
      Epithelial Crypt (LEC) that has features of a putative stem cell niche. In this
      study we examined infant limbus tissue (donor age 4 months) for evidence of LEC
      and performed immunohistological comparison between infant limbus and adult LEC.
      No defined LEC were detected in the infant limbus. However, the entire infant
      limbus has characteristics resembling adult LEC. Both infant limbus and LEC
      demonstrated negative expression for desmoglein 3. p63 and integrin beta1
      expressions were located to the distal region of the infant limbus and to the
      basal region of the LEC. ABCG2 expression was positive throughout most of the
      infant limbus as was connexin 43. Infant limbus and in particular the distal
      region, appeared to house cells that are more "stem-like" in nature. The LEC may
      be a result of normal physiological developmental in order to protect and
      maintain stem cells at the ocular surface.

PMID- 19176217
TI  - New highly specific botulinum type C1 endopeptidase immunoassays utilising SNAP25
      or Syntaxin substrates.
AB  - Botulinum neurotoxins contain proteases that cleave specific intra-neural
      proteins essential for neurotransmitter release. Toxin types A, C1 and E intra
      cellularly cleave SNAP25 and/or Syntaxin (type C1 only) resulting in a flaccid
      paralysis. Although highly sensitive, robust in vitro endopeptidase immunoassays
      have been developed for some serotypes, an endopeptidase immunoassay for type C1
      has not previously been described. The current studies utilised solid phase
      synthesized SNAP25(137-206) peptide substrate, and a new specific antibody to the
      SNAP25(191-198) octapeptide epitope that becomes exposed following cleavage by
      type C1 toxin. The highly specific nature of the detecting antibody was
      illustrated by the failure of anti-SNAP25(191-198) to recognise the type A
      cleavage product which differs by just one amino acid residue. Conversely, anti
      SNAP25(190-197), which recognises the type A cleavage product, fails to cross
      react with the type C1 toxin cleavage product. Utilising Syntaxin(232-266)
      peptide substrate, and a specific antibody to the cleavage product epitope,
      Syntaxin(254-261), it was also possible to develop an endopeptidase immunoassay.
      Assay sensitivities allowed the detection of less than 0.1 LD(50)/ml (25 pg/ml)
      of type C1 haemagglutinin-complexed toxin. The assay failed to detect toxin
      serotypes A, B, D, E, F or G and therefore also provides an alternative highly
      specific in vitro identity test. In the absence of trypsin inhibitors, the assay
      is also capable of detecting 2 pg/ml of trypsin activity, or trypsin like
      contaminants. These new immunoassays will therefore provide highly specific tools
      for monitoring botulinum toxin light chain endopeptidase activity and serotype
      identity.

PMID- 19176218
TI  - Animal models for the study of influenza pathogenesis and therapy.
AB  - Influenza A viruses causes a variety of illnesses in humans. The most common
      infection, seasonal influenza, is usually a mild, self-limited febrile syndrome,
      but it can be more severe in infants, the elderly, and immunodeficient persons,
      in whom it can progress to severe viral pneumonitis or be complicated by
      bacterial superinfection, leading to pneumonia and sepsis. Seasonal influenza
      also occasionally results in neurologic complications. Rarely, viruses that have
      spread from wild birds to domestic poultry can infect humans; such "avian
      influenza" can range in severity from mild conjunctivitis through the rapidly
      lethal disease seen in persons infected with the H5N1 virus that first emerged in
      Hong Kong in 1997. To develop effective therapies for this wide range of
      diseases, it is essential to have laboratory animal models that replicate the
      major features of illness in humans. This review describes models currently in
      use for elucidating influenza pathogenesis and evaluating new therapeutic agents.

PMID- 19176220
TI  - Effects of injection of biogenic amines on expression of gill related ion
      transporter mRNA and alpha-subunit protein in Litopenaeus vannamei.
AB  - We used semi-quantitative reverse transcription and the polymerase chain reaction
      (RT-PCR) to identify and characterize the mRNA of Na(+)/K(+)-ATPase alpha-subunit
      and Vacuolar-type H/-ATPase (V-ATPase) beta-subunit prepared from gills of the
      white shrimp Litopenaeus vannamei. Western blot and immunocytochemistry analysis
      were employeed to investigate the effects of biogenic amines such as dopamine
      (DA) and 5-hydroxytryptamine (5-HT) injection on expression of protein abundance
      and immunostained sites. Our results show that the gill Na(+)/K(+)-ATPase of 5-HT
      treatments increased lag to those of DA treatments. However, the DA and 5-HT have
      no significant effects on the activity of V-ATPase. The biogenic amines could
      induce the synthesis of Na(+)/K(+)-ATPase alpha-subunit mRNA in the first 12 h.
      The degree of change in Na(+)/K(+)-ATPase alpha-subunit mRNA expression were
      different between DA and 5-HT treated groups which depend on the dose. The
      expression of V-ATPase beta-subunit mRNA was not markedly affected by the
      biogenic amines. Concomitant elevation of Na(+)/K(+)-ATPase activity, alpha
      subunit mRNA as well as protein abundance in response to injected biogenic amines
      was also found in Na(+)/K(+)-ATPase immunostained sites within the gill
      epithelium.

PMID- 19176222
TI  - A schema-focused approach to group psychotherapy for outpatients with borderline
      personality disorder: a randomized controlled trial.
AB  - This study tests the effectiveness of adding an eight-month, thirty-session
      schema-focused therapy (SFT) group to treatment-as-usual (TAU) individual
      psychotherapy for borderline personality disorder (BPD). Patients (N=32) were
      randomly assigned to SFT-TAU and TAU alone. Dropout was 0% SFT, 25% TAU.
      Significant reductions in BPD symptoms and global severity of psychiatric
      symptoms, and improved global functioning with large treatment effect sizes were
      found in the SFT-TAU group. At the end of treatment, 94% of SFT-TAU compared to
      16% of TAU no longer met BPD diagnosis criteria (p<.001). This study supports
      group SFT as an effective treatment for BPD that leads to recovery and improved
      overall functioning.

PMID- 19176219
TI  - The transport of anti-HIV drugs across blood-CNS interfaces: summary of current
      knowledge and recommendations for further research.
AB  - The advent of highly active antiretroviral therapy (HAART), which constitutes HIV
      protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside
      reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors,
      has dramatically reduced the morbidity and mortality associated with human
      immunodeficiency virus (HIV) infection in resource-rich countries. However, this
      disease still kills several million people each year. Though the reason for
      therapeutic failure is multi-factorial, an important concern is the treatment and
      control of HIV within the central nervous system (CNS). Due to the restricted
      entry of anti-HIV drugs, the brain is thought to form a viral sanctuary site.
      This not only results in virological resistance, but also is often associated
      with the development of complications such as HIV-associated dementia. The CNS
      delivery of anti-HIV drugs is limited by the blood-brain and blood-CSF interfaces
      due to a combination of restricted paracellular movement, powerful metabolic
      enzymes and numerous transporters including members of the ATP binding cassette
      (ABC) and solute carrier (SLC) superfamilies. A better appreciation of the
      transporters present at the brain barriers will prove a valuable milestone in
      understanding the limited brain penetration of anti-HIV drugs in HIV and also aid
      the development of new anti-HIV drugs and drug combinations, with enhanced
      efficacy in the CNS. This review aims to summarise current knowledge on the
      transport of anti-HIV drugs across the blood-brain barrier and the choroid
      plexus, as well as provide recommendations for future research.

PMID- 19176223
TI  - The p21 codon 31*C- and DRD2 codon 313*T-related genotypes/alleles, but not XRCC1
      codon 399, hOGG1 codon 326, and DRD1-48 polymorphisms, are correlated with the
      presence of leiomyoma.
AB  - OBJECTIVE: To investigate whether the gene polymorphisms for p21, X-ray repair
      cross-complementing group 1 (XRCC1), human 8-oxoguanine glycosylase 1 (hOGG1),
      and dopamine D1 and D2 receptors (DRD1, -2) are associated with leiomyoma
      susceptibility. DESIGN: Prospective study. SETTING: Departments of gynecology and
      genetics in a medical center. PATIENT(S): Women were divided into two groups:
      leiomyoma (n = 120) and nonleiomyoma (n = 112). INTERVENTION(S): The p21 codon
      31, XRCC1 codon 399, hOGG1 codon 326, DRD1-48, and DRD2 codon 313 polymorphisms
      were genotyped by polymerase chain reaction with restriction enzyme digestions
      (Blp I, MspI, Fnu4HI, Dde I, and NcoI, respectively). MAIN OUTCOME MEASURE(S):
      Genotypes and allelic frequencies. RESULT(S): The p21 codon 31(*)C- and DRD2
      codon 313(*)T-related genotypes/alleles were associated with the presence of
      leiomyomas. The proportions of p21(*)CC/CA/AA and DRD2(*)CC/CT/TT in both groups
      were 27.5/68.3/4.2% and 12.5/51.7/35.8% (leiomyoma); and 14.3/51.8/33.9% and
      33.9/40.2/25.9% (nonleiomyoma). XRCC1, hOGG1, and DRD1 were not correlated with
      the presence of leiomyomas. XRCC1(*)GG/GA/AA, hOGG1(*)TT/TA/AA, and
      DRD1(*)GG/GA/AA were 54.2/37.5/8.3%, 36.7/44.2/19.1%, and 3.3/25.8/70.8%
      (leiomyoma); and 48.2/47.3/4.5%, 43.6/41/15.4%, and 3.6/25/71.4% (nonleiomyoma).
      CONCLUSION(S): The p21 codon 31(*)C- and DRD2 codon 313(*)T-related
      genotypes/alleles were associated with the presence of leiomyoma. XRCC1, hOGG1,
      and DRD1 were not correlated with leiomyoma development.

PMID- 19176224
TI  - Diagnosis of an autoamputated ovary with dermoid cyst during a Cesarean section.
AB  - OBJECTIVE: To report an extremely rare case of an autoamputated ovary with a
      dermoid cyst diagnosed during a Cesarean section and review the literature.
      DESIGN: Case report. SETTING: Tertiary hospital. PATIENT(S): A 33-year-old
      pregnant woman submitted to Cesarean section and was incidentally diagnosed with
      absence of the right ovary, implanted in the cul-de-sac. INTERVENTION(S):
      Cesarean section and extraction of a pedunculated tumor formation from the cul-de
      sac, adhesiolysis. MAIN OUTCOME MEASURE(S): Histologic analysis of the extracted
      morphoma confirmed the diagnosis of a dermoid cyst with coexistence of residual
      ovarian tissue. RESULTS: The patient had an uneventful postpartum period and was
      discharged home. CONCLUSION(S): Ovarian autoamputation is an extremely rare
      phenomenon that has uncertain etiology; it may develop after ovarian torsion or
      torsion of a dermoid cyst. It may be asymptomatic. Usual site of implantation is
      the greater omentum.

PMID- 19176225
TI  - Prediction of iodide adsorption on oxides by surface complexation modeling with
      spectroscopic confirmation.
AB  - A deficiency in environmental iodine can cause a number of health problems.
      Understanding how iodine is sequestered by materials is helpful for evaluating
      and developing methods for minimizing human health effects related to iodine. In
      addition, (129)I is considered to be strategically important for safety
      assessment of underground radioactive waste disposal. To assess the long-term
      stability of disposed radioactive waste, an understanding of (129)I adsorption on
      geologic materials is essential. Therefore, the adsorption of I(-) on naturally
      occurring oxides is of environmental concern. The surface charges of hydrous
      ferric oxide (HFO) in NaI electrolyte solutions were measured by potentiometric
      acid-base titration. The surface charge data were analyzed by means of an
      extended triple-layer model (ETLM) for surface complexation modeling to obtain
      the I(-) adsorption reaction and its equilibrium constant. The adsorption of I(-)
      was determined to be an outer-sphere process from ETLM analysis, which was
      consistent with independent X-ray absorption near-edge structure (XANES)
      observation of I(-) adsorbed on HFO. The adsorption equilibrium constants for I(
      ) on beta-TiO(2) and gamma-Al(2)O(3) were also evaluated by analyzing the surface
      charge data of these oxides in NaI solution as reported in the literature.
      Comparison of these adsorption equilibrium constants for HFO, beta-TiO(2), and
      gamma-Al(2)O(3) based on site-occupancy standard states permitted prediction of
      I(-) adsorption equilibrium constants for all oxides by means of the Born
      solvation theory. The batch adsorption data for I(-) on HFO and amorphous
      aluminum oxide were reasonably reproduced by ETLM with the predicted equilibrium
      constants, confirming the validity of the present approach. Using the predicted
      adsorption equilibrium constants, we calculated distribution coefficient (K(d))
      values for I(-) adsorption on common soil minerals as a function of pH and ionic
      strength.

PMID- 19176226
TI  - Influence of colloidal interactions on pigment coating layer structure formation.
AB  - The consolidation of pigment coating layers was simulated using a three
      dimensional particle dynamics model. The model included hydrodynamic interactions
      as well as colloidal force models and the Brownian motion. The impact of various
      colloidal model parameters on the z-direction solids profile development and
      coating layer thickness was investigated. Also, the influence of continuous
      (liquid) phase viscosity was tested. Particle systems resembling a polydisperse
      ground calcium carbonate (GCC) distribution were studied. Results show that a
      lower particle surface potential on pigments increased the thickness of the
      coating layer, while the electrostatic double layer thickness influenced the
      internal coating structure. An increased viscosity of the continuous phase slowed
      the consolidation down, but did not have a significant impact on the final
      microstructure. The work contributes to the understanding of the influence of
      colloidal system properties on the consolidation and structure development of
      coating layers. The results may aid in the understanding of the impact of
      chemical additives on coating layer structure formation.

PMID- 19176227
TI  - Electrocardiographic criteria for detecting coronary artery disease in
      hypertensive patients with ST-segment changes during exercise testing.
AB  - PURPOSE: It is well known that patients with arterial hypertension frequently
      present with ischemic electrocardiographic changes during exercise testing
      without actually having coronary artery disease (CAD). The purpose of this study
      was to establish additional electrocardiographic criteria during exercise testing
      for detecting CAD in hypertensive patients with ischemic ST-segment response.
      METHODS: Three hundred eighty-two consecutive hypertensive patients (224 males,
      58 +/- 8 years) who presented with ischemic electrocardiographic changes during
      exercise testing and agreed to undergo coronary arteriography were included in
      the study. RESULTS: From 382 hypertensive patients undergoing coronary
      angiography, only 76 (20%) had significant coronary stenosis, whereas 306 (80%)
      had normal coronary arteries. From 382 patients, 287 (75%) (group A) presented
      with ST-segment depression during exercise in leads II-III-aVF-V(6), 271 (94%) of
      which had normal arteries at the angiography. The remaining 95 patients (25%)
      (group B) of the studied patients presented with ST-segment depression in II-III
      aVF and/or V(4) through V(6), 60 (63%) of which had CAD. Furthermore, 251
      patients of group A presented with ST-segment depression during the fourth to
      sixth minute of the recovery period in V(4) through V(6), 247 (98%) of which had
      normal arteries. Another 28 patients from group B presented with ST-segment
      depression during the fourth to eighth minute of the recovery period in V(4)
      through V(6), 22 (79%) of which had significant coronary artery stenosis.
      CONCLUSIONS: Hypertensive patients who present with ST-segment depression during
      exercise in leads II-III-aVF and/or V(4) through V(6) and with a prolonged
      duration of this depression at the recovery phase (fourth to eighth minute) are
      more likely to have CAD. Absence of ST-segment depression in V(4) and V(5) at the
      end of exercise or during the seventh and eighth minute of recovery favors a
      false-positive result.

PMID- 19176228
TI  - Possible Parkinson's disease revealed by a pure head resting tremor.
AB  - Head tremor is very unusual in Parkinson's disease (PD). Five PD patients
      presenting a head tremor during the disease evolution have recently been
      reported. Here we describe a 74 year-old woman with a pure head resting tremor.
      The tremor was responsive to levodopa and had a 4.7 Hz frequency. A [(123)I]FP
      CIT SPECT imaging confirmed a reduction of tracer uptake in the right striatum
      consistent with PD, that should be confirmed by long-term follow-up.

PMID- 19176229
TI  - Reduced NADH coenzyme Q dehydrogenase activity in platelets of Parkinson's
      disease, but not Parkinson plus patients, from an Indian population.
AB  - The observation of decline in mitochondrial electron transport chain function,
      specifically at complex I, in patients with Parkinson's disease (PD) has been
      reported by several groups. This study investigates whether a defect of
      mitochondrial function is present in the platelets of PD patients from an Indian
      population. We found that the NADH dehydrogenase activity in the platelets of PD
      patients is lower than that in healthy age- and gender-matched controls, while
      the succinate dehydrogenase activity was similar in both groups. Furthermore,
      there was no change in either of the activities in patients with Parkinson plus
      syndrome or atypical parkinsonism. This is the first report indicating a decline
      in mitochondrial function in the platelets of PD patients from the Indian
      population, offering further support to the role of a mitochondrial defect in PD.

PMID- 19176230
TI  - Walleye dermal sarcoma virus rv-cyclin inhibits NF-kappaB-dependent
      transcription.
AB  - The retroviral cyclin protein (rv-cyclin) of walleye dermal sarcoma virus
      contains two known functional domains, a cyclin box motif and a carboxy terminal
      transcription activation domain (AD). The AD contacts TATA-binding protein
      associated factor 9 (TAF9), and this action is necessary for both positive and
      negative regulation of transcription from host and viral promoters. Negative
      regulation occurs via interference with TAF9 binding by transcriptional
      activators. Transcription factors that share a functional TAF9-binding motif
      include NF-kappaB. Rv-cyclin down regulates NF-kappaB-dependent transcription,
      whether induced by TNFalpha or by direct phosphorylation of IkappaB by expressed
      MEKK1. In rv-cyclin-expressing cells, NF-kappaB p65 is phosphorylated and
      translocated to the nucleus, where it forms heterodimers with p50 and binds NF
      kappaB response elements. Furthermore, interference with NF-kappaB is dependent
      upon an intact TAF9-binding motif in rv-cyclin. The outcome of this NF-kappaB
      down regulation is likely to be important in the control of virus replication and
      tumorigenesis.

PMID- 19176231
TI  - Monitoring of opiates, cannabinoids and their metabolites in wastewater, surface
      water and finished water in Catalonia, Spain.
AB  - The occurrence of several opiates and cannabinoids in wastewaters and surface
      waters has been investigated. Most of the compounds (8 out of 11) were identified
      in both influent and effluents of fifteen wastewater treatment plants (WWTPs).
      Codeine, morphine, EDDP and methadone were detected in almost all samples with
      median values of 69ng/L; 63ng/L; 28ng/L and 18ng/L, respectively, whereas the
      main cannabinoid metabolite THC-COOH presented a median value of 57ng/L in
      influents. A rough estimate of heroin and cannabis consumption was performed from
      the analysis of target urinary metabolites in wastewater influents. Data obtained
      from influents of rural and urban WWTPs gave 0.07% of heroin consumption (0.67%
      for the largest urban WWTP) and 4% consumption of cannabinoids, respectively for
      the population aged between 15 and 64 years old. The presence of opiates and
      cannabinoids in surface waters used for drinking water production showed the
      presence of the same compounds identified in wastewater effluents at
      concentrations up to 76ng/L for codeine; 31ng/L for EDDP; 12ng/L for morphine and
      9ng/L for methadone at the intake of the DWTP. A complete removal of all studied
      drugs present in surface water was achieved during the potabilization process
      except for methadone and EDDP (91% and 87% removal, respectively).

PMID- 19176232
TI  - Extension of ASM3 for two-step nitrification and denitrification and its
      calibration and validation with batch tests and pilot scale data.
AB  - Although traditionally not taken into account by most of activated sludge models
      the production of nitrite as an intermediate of the nitrification-denitrification
      processes becomes of interest in some specific plant operational situations or in
      case of high sensitivity of the receiving ecosystems. The Activated Sludge Model
      No.3 (ASM3) was therefore extended for two-step nitrification and two-step
      denitrification in order to better describe nitrite dynamics especially during
      the treatment of communal wastewater. Nitrite was included as a new model
      compound and as an intermediate product of biological processes, both for
      heterotrophic and autotrophic bacteria. Two new model compounds replace X(A), the
      original autotrophic biomass: Ammonium Oxidizing Bacteria, X(AOB) and Nitrite
      Oxidizing Bacteria, X(NOB). Growth and decay processes of nitrifiers were split
      into AOB and NOB processes (3 additional processes) and heterotrophic anoxic
      processes were also doubled in order to account for two-step denitrification (4
      additional processes). Default values from literature as well as laboratory
      measurements were considered for the choice of kinetic and stoichiometric
      parameters. The model was calibrated and validated with laboratory scale tests in
      batch reactors and with data from an Eawag activated sludge pilot plant
      configured conventionally with nitrification and pre-denitrification for the
      treatment of communal wastewater.

PMID- 19176233
TI  - Conditions required for the stimulation of bioluminescence activity of the
      genetically engineered bacteria, P. putida mt-2 KG1206, preserved by deep
      freezing.
AB  - Herein the conditions required for the stimulation of bioluminescence activity in
      a genetically engineered strain of Pseudomonas putida mt-2 KG1206, containing the
      intact TOL plasmid and a constructed plasmid with the P(m)-lux gene, are reported
      upon. Both sodium lactate (SL) and potassium nitrate (KNO(3)) were able to
      stimulate the bioluminescence activity, but a greater increase was observed with
      nitrogen amendment. This selected stimulant was then tested on reconstituted
      cells that had been preserved by deep-freezing and mixed with pure inducer
      solution or groundwater samples. The stimulation of bioluminescence activities
      for deep-frozen strain was in the range of 101-238% of the control. The effect of
      KNO(3) was found to be dependent on the type of inducers used and the cell
      conditions. In general, high bioluminescence activity was observed with
      groundwater samples, contaminated with high inducer compounds. However, no
      significant correlation was observed between the bioluminescence intensity and
      the total inducer concentration in the environmental samples contaminated with
      complex mixtures with inducers. These results should be useful when other
      recombinant bioluminescence strains are to be used for environmental monitoring.
      Overall, the results of this study demonstrate the stimulant conditions for the
      bioluminescence activity of genetically engineered bacteria, and suggest the
      potential for preliminary application of this deep-frozen engineered strain in a
      field-ready bioassay to conveniently detect or monitor a specific group of
      environmental contaminants.

PMID- 19176234
TI  - Infrared spectroscopy tracing of sediment sources in a small rural watershed
      (French Alps).
AB  - The present article describes a first attempt to use infrared spectroscopy to
      trace the origin of suspended river sediments. Fifty samples of the main
      potential sediment sources within a small catchment area (990 ha) in the French
      Alps were collected and compared with samples of suspended sediment from the
      river, collected on various dates during 2006 and 2007 using sediment traps. Two
      major categories of sediment source were identified: topsoils and river channel
      sediments. For the qualitative part of the study, each of these two main
      categories was divided into two sub-categories, that is to say, cultivated and
      pastureland topsoils, and riverbed and riverbank sediments. Discriminant analysis
      on the source samples showed that Diffuse Reflectance Infrared Fourier Transform
      (DRIFT) spectroscopy can be used to differentiate between the four potential
      source materials. To determine whether or not immersion in the river altered the
      infrared spectra of these source materials, we measured the infrared spectra of
      samples that had been immersed in the river, in litter bags, for periods of up to
      24 days. Immersion did not cause any major changes in the infrared spectra. The
      contribution of each type of source material to the suspended sediment in the
      river was quantified using partial least squares (PLS) analyses of DRIFT spectra
      to compare actual river sediment samples with an experimental model. This model
      was produced from the DRIFT spectra of a range of calibration samples produced by
      mixing source material samples in different ratios. The predictions of the model
      were valid and fell within the confidence interval calculated for the calibration
      set. Comparisons between suspended sediment samples and the model indicate that
      the predominant source of the sediment is riverbank erosion, which, in this case,
      is probably due to trampling by cattle.

PMID- 19176235
TI  - Ileal orthotopic neobladder after pelvic exenteration for cervical cancer.
AB  - OBJECTIVE: We aimed to describe our preliminary experience in creating an ileal
      orthotopic urinary conduit in patients with a history of pelvic irradiation
      undergoing pelvic exenteration for recurrent cervical cancer and to evaluate the
      feasibility, complication rates, and outcomes of this procedure. METHODS: A
      retrospective chart review was performed in all 6 patients who underwent ileal
      orthotopic neobladder creation at our institution between January 2005 and March
      2008. Main outcome measures were surgical complications, continence rate,
      neobladder function, and oncologic outcome. RESULTS: The mean patient age was
      46.6 years (range, 38-61). Four patients underwent anterior exenteration and 2
      total pelvic exenterations. There were no intraoperative complications. The
      median operative time was 456 min (range, 372-600). The median time to create the
      orthotopic urinary conduit was 70 min (range, 55-90). Three patients had
      postoperative neobladder anastomotic leak. Two of them had this complication
      successfully managed conservatively and 1 surgically. Daytime urinary continence
      was good or satisfactory in 4 of 6 patients. Nighttime urinary continence was
      good or satisfactory in 3 of 6 patients. All patients reported being satisfied
      with their decision to undergo this procedure. Median follow-up time was 20.5
      months (range, 6-34). At last visit, 3 patients were alive without evidence of
      disease, 1 was alive with stable retroperitoneal disease, and 2 had died of
      disease recurrence after exenteration. CONCLUSIONS: Ileal orthotopic neobladder
      creation in patients undergoing exenteration for recurrent cervical cancer is
      feasible after radiation. The rate of urinary continence is acceptable.

PMID- 19176236
TI  - Is centralization of ovarian cancer care warranted? A cost-effectiveness
      analysis.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of tertiary referral care for
      ovarian cancer patients in the Netherlands. METHODS: We collected clinical and
      registry data on 1077 newly diagnosed ovarian cancer patients treated from 1996
      2003 in a random sample of Dutch hospitals. Decision modelling was used to
      compare the cost-effectiveness of treatment in general hospitals, semi
      specialized hospitals, and tertiary care centers. The actual direct medical costs
      of ovarian cancer treatment were evaluated. Long-term outcomes in terms of costs,
      quality-adjusted life-years (QALYs), and incremental costs per QALY gained were
      estimated. To assess uncertainty, multivariable sensitivity analyses and scenario
      analyses were performed. RESULTS: Treatment of ovarian cancer patients in semi
      specialized hospitals costs on average euro882 more than in general hospitals
      (95% confidence interval -720 to 2462) and yields 0.12 additional QALYs (95% CI
      0.02 to 0.22), resulting in an incremental cost-effectiveness ratio (ICER) of
      euro7135. Patients treated in tertiary care centers incurred again higher costs
      (euro10,591, 95% CI 8757 to 12,480) and also higher QALYs (0.10, 95% CI 0 to
      0.21), resulting in an ICER of euro102,642 compared to semi-specialized
      hospitals. If the optimal debulking rate in tertiary care centers would increase
      to 70%, costs could drop below euro30,000 per QALY. CONCLUSION: Current treatment
      of ovarian cancer patients in semi-specialized hospital settings is a cost
      effective strategy, while treatment in tertiary care centers becomes only cost
      effective when better surgical results would be achieved.

PMID- 19176237
TI  - Robotic radical hysterectomy: Technical aspects.
AB  - OBJECTIVES: To describe the surgical technique of robotic radical hysterectomy.
      METHODS: Retrospective video review of the instrumentation and methodology
      employed in 21 robotic radical hysterectomies for cervical cancer Stages IB-IIA.
      RESULTS: All radical hysterectomies were performed with the use of three or four
      robotic arms, three or four robotic instruments and one assistant trocar. The
      mean operating time was 225.8 min; mean console time was 182.1 min; and mean
      docking time was 2.2 min. The mean blood loss was 174.6 ml, mean number of lymph
      nodes 26.2, and the mean length of hospital stay was 1.6 days. CONCLUSIONS:
      Robotic technology facilitates the performance of robotic radical hysterectomy.

PMID- 19176238
TI  - Hyperthermic intraperitoneal chemotherapy in the management of ovarian cancer: A
      critical need for an evidence-based evaluation.

PMID- 19176239
TI  - The ongoing enigma of tight glucose control.

PMID- 19176240
TI  - Intensive insulin therapy for patients in paediatric intensive care: a
      prospective, randomised controlled study.
AB  - BACKGROUND: Critically ill infants and children often develop hyperglycaemia,
      which is associated with adverse outcome; however, whether lowering blood glucose
      concentrations to age-adjusted normal fasting values improves outcome is unknown.
      We investigated the effect of targeting age-adjusted normoglycaemia with insulin
      infusion in critically ill infants and children on outcome. METHODS: In a
      prospective, randomised controlled study, we enrolled 700 critically ill
      patients, 317 infants (aged <1 year) and 383 children (aged >or=1 year), who were
      admitted to the paediatric intensive care unit (PICU) of the University Hospital
      of Leuven, Belgium. Patients were randomly assigned by blinded envelopes to
      target blood glucose concentrations of 2.8-4.4 mmol/L in infants and 3.9-5.6
      mmol/L in children with insulin infusion throughout PICU stay (intensive group
      [n=349]), or to insulin infusion only to prevent blood glucose from exceeding
      11.9 mmol/L (conventional group [n=351]). Patients and laboratory staff were
      blinded to treatment allocation. Primary endpoints were duration of PICU stay and
      inflammation. Analysis was by intention to treat. This study is registered with
      ClinicalTrials.gov, number NCT00214916. FINDINGS: Mean blood glucose
      concentrations were lower in the intensive group than in the conventional group
      (infants: 4.8 [SD 1.2] mmol/L vs 6.4 [1.2] mmol/L, p<0.0001; children: 5.3 [1.1]
      mmol/L vs 8.2 [3.3] mmol/L, p<0.0001). Hypoglycaemia (defined as blood glucose
      <or=2.2 mmol/L) occurred in 87 (25%) patients in the intensive group (p<0.0001)
      versus five (1%) patients in the conventional group; hypoglycaemia defined as
      blood glucose less than 1.7 mmol/L arose in 17 (5%) patients versus three (1%)
      (p=0.001). Duration of PICU stay was shortest in the intensively treated group
      (5.51 days [95% CI 4.65-6.37] vs 6.15 days [5.25-7.05], p=0.017). The
      inflammatory response was attenuated at day 5, as indicated by lower C-reactive
      protein in the intensive group compared with baseline (-9.75 mg/L [95% CI -19.93
      to 0.43] vs 8.97 mg/L [-0.9 to 18.84], p=0.007). The number of patients with
      extended (>median) stay in PICU was 132 (38%) in the intensive group versus 165
      (47%) in the conventional group (p=0.013). Nine (3%) patients died in the
      intensively treated group versus 20 (6%) in the conventional group (p=0.038).
      INTERPRETATION: Targeting of blood glucose concentrations to age-adjusted normal
      fasting concentrations improved short-term outcome of patients in PICU. The
      effect on long-term survival, morbidity, and neurocognitive development needs to
      be investigated. FUNDING: Research Foundation (Belgium); Research Fund of the
      University of Leuven (Belgium) and the EU Information Society Technologies
      Integrated project "CLINICIP"; and Institute for Science and Technology
      (Belgium).

PMID- 19176241
TI  - Pharmacokinetics and biodistribution of N-isopropylacrylamide copolymers for the
      design of pH-sensitive liposomes.
AB  - The purpose of this work was to characterize the pharmacokinetics (PK) and
      biodistribution of pH-responsive N-isopropylacrylamide (NIPAAm) copolymers, and
      to determine the impact of some physicochemical parameters on their biological
      profiles. Radiolabeled copolymers of NIPAAm and methacrylic acid (MAA) of
      different molecular weight, amphiphilicity and lower critical solution
      temperature (LCST) were synthesized and injected intravenously to rats. The PK
      and excretion profiles were monitored over 48 h. It was found that elimination
      occurred mainly through urinary excretion, which was principally governed by
      molecular weight. Above a threshold of 32,000, the polymer chains avoided
      glomerular filtration and presented prolonged circulation times. Moreover, the
      presence of alkyl moieties at the chain extremity influenced circulation time and
      tissue distribution of polymer chains, hypothetically through formation of
      micellar structures. The polymers with an LCST situated below the physiological
      temperature did not circulate for prolonged periods in the bloodstream and were
      highly captured by the organs of the mononuclear phagocyte system. Finally, the
      complexation of an alkylated pH-sensitive polymer with a molecular weight of
      10,000 to the bilayer of PEGylated liposomes produced a drastic change in the PK
      parameters, indicating that the polymer remained anchored in the phospholipid
      bilayer in the bloodstream. These data indicate that stable pH-sensitive
      liposomes can be produced using excretable NIPAAm copolymers.

PMID- 19176242
TI  - Injectable chitosan-based hydrogels for cartilage tissue engineering.
AB  - Water-soluble chitosan derivatives, chitosan-graft-glycolic acid (GA) and
      phloretic acid (PA) (CH-GA/PA), were designed to obtain biodegradable injectable
      chitosan hydrogels through enzymatic crosslinking with horseradish peroxidase
      (HRP) and H2O2. CH-GA/PA polymers were synthesized by first conjugating glycolic
      acid (GA) to native chitosan to render the polymer soluble at pH 7.4, and
      subsequent modification with phloretic acid (PA). The CH-GA43/PA10 with a degree
      of substitution (DS, defined as the number of substituted NH2 groups per 100
      glucopyranose rings of chitosan) of GA of 43 and DS of PA of 10 showed a good
      solubility at pH values up to 10. Short gelation times (e.g. 10 s at a polymer
      concentration of 3 wt%), as recorded by the vial tilting method, were observed
      for the CH-GA43/PA10 hydrogels using HRP and H2O2. It was shown that these
      hydrogels can be readily degraded by lysozyme. In vitro culturing of chondrocytes
      in CH-GA43/PA10 hydrogels revealed that after 2 weeks the cells were viable and
      retained their round shape. These features indicate that CH-GA/PA hydrogels are
      promising as an artificial extracellular matrix for cartilage tissue engineering.

PMID- 19176243
TI  - The influence of three-dimensional nanofibrous scaffolds on the osteogenic
      differentiation of embryonic stem cells.
AB  - Embryonic stem cells represent a potentially unlimited cell source for tissue
      engineering applications. However, in order to be used for such applications,
      embryonic stem cells' differentiation must be controlled to only the desired
      lineages. In this study, we examine the effects of nanofibrous architecture and
      biochemical cues on the osteogenic differentiation of embryonic stem cells
      compared to the more traditional architecture without the nanofibrous features in
      two dimensions (thin matrix or flat films) and three dimensions (scaffolds) in
      vitro. After three weeks of culture the nanofibrous thin matrices were capable of
      supporting mRNA expression of osteogenic differentiation markers in embryonic
      stem cells without osteogenic supplements, while solid films required osteogenic
      supplements and growth factors to achieve mRNA expression of osteogenic
      differentiation markers. Nanofibrous scaffolds substantially enhanced mRNA
      expression of osteogenic differentiation markers compared to solid-walled
      scaffolds, nanofibrous thin matrices or solid films. After 4 weeks of culture,
      nanofibrous scaffolds were found to contain 3 times more calcium and stronger
      osteocalcin stain throughout the scaffolds than the solid-walled scaffolds.
      Overall, the nanofibrous architecture enhanced the osteogenic differentiation and
      mineralization of embryonic stem cells compared to the solid-walled architecture
      in both two and three-dimensional cultures.

PMID- 19176244
TI  - In vivo evaluation of safety and efficacy of self-assembled nanoparticles for
      oral insulin delivery.
AB  - A variety of approaches have been studied in the past to overcome the problems
      encountered with the oral delivery of insulin, but with little success. In this
      study, self-assembled nanoparticles (NPs) with a pH-sensitive characteristic were
      prepared by mixing the anionic poly-gamma-glutamic acid solution with the
      cationic chitosan solution in the presence of MgSO(4) and sodium
      tripolyphosphate. The in vitro results found that the transport of insulin across
      Caco-2 cell monolayers by NPs appeared to be pH-dependent; with increasing pH,
      the amount of insulin transported decreased significantly. An in vivo toxicity
      study was performed to establish the safety of the prepared NPs after oral
      administration. Additionally, the impact of orally administered NPs on the
      pharmacodynamics (PD) and pharmacokinetics (PK) of insulin was evaluated in a
      diabetic rat model. The in vivo results indicated that the prepared NPs could
      effectively adhere on the mucosal surface and their constituted components were
      able to infiltrate into the mucosal cell membrane. The toxicity study indicated
      that the NPs were well tolerated even at a dose 18 times higher than that used in
      the PD/PK study. Oral administration of insulin-loaded NPs demonstrated a
      significant hypoglycemic action for at least 10h in diabetic rats and the
      corresponding relative bioavailability of insulin was found to be 15.1+/-0.9%.
      These findings suggest that the NPs prepared in the study are a promising vehicle
      for oral delivery of insulin.

PMID- 19176245
TI  - The penetration of fresh undiluted sputum expectorated by cystic fibrosis
      patients by non-adhesive polymer nanoparticles.
AB  - Highly viscoelastic and adhesive sputum has precluded efficient nanoparticle
      based drug and gene delivery to the lungs of patients with cystic fibrosis (CF).
      We sought to determine whether nanoparticles coated with non-mucoadhesive
      polymers could penetrate CF sputum, and to use these "muco-inert particles"
      (MIPs) as non-destructive nanoprobes to characterize the sputum microstructure.
      Particles as large as 200 nm in diameter that were densely coated with low MW
      polyethylene glycol (PEG) moved through undiluted CF sputum with average speeds
      up to 90-fold faster than similarly-sized uncoated particles. On the other hand,
      the transport of both coated and uncoated 500 nm particles was strongly hindered.
      The local viscosity of sputum, encountered by the fastest 10% of 200 nm MIPs, was
      only 5-fold higher than that of water, whereas the bulk viscosity was 10,000-fold
      higher at low shear rates. Using measured transport rates of various sized MIPs
      combined with an obstruction-scaling model, we determined that the average 3D
      mesh spacing of CF sputum is approximately 140+/-50 nm (range: 60-300 nm). Taken
      together, these results demonstrate that nanoparticles up to 200 nm in diameter
      that do not adhere to CF sputum can move rapidly through this critical barrier by
      accessing pores that are filled with a low viscosity fluid. The results also
      offer hope that desperately needed sputum-penetrating drug- and gene-carrier
      nanoparticles can be developed for CF.

PMID- 19176246
TI  - Can bioactivity be tested in vitro with SBF solution?
AB  - A large part of the scientific community has accepted the paradigm that a
      simulated body solution (SBF) can be used to test the bioactivity of a material.
      This is exemplified by the rapidly increasing number of publications using this
      test. The aim of this document is to demonstrate that (i) there is presently not
      enough scientific data to support this assumption, and (ii) even though the
      assumption was valid, the way the test is generally conducted leaves room for
      improvement. Theoretical arguments and facts supporting these statements are
      provided, together with possible improvements of the proposed bioactivity test.

PMID- 19176248
TI  - Identification of Mycobacterium avium KatG protein (MAV_2753) as a possible
      serodiagnostic marker for MAC disease.

PMID- 19176247
TI  - Organ printing: tissue spheroids as building blocks.
AB  - Organ printing can be defined as layer-by-layer additive robotic biofabrication
      of three-dimensional functional living macrotissues and organ constructs using
      tissue spheroids as building blocks. The microtissues and tissue spheroids are
      living materials with certain measurable, evolving and potentially controllable
      composition, material and biological properties. Closely placed tissue spheroids
      undergo tissue fusion - a process that represents a fundamental biological and
      biophysical principle of developmental biology-inspired directed tissue self
      assembly. It is possible to engineer small segments of an intraorgan branched
      vascular tree by using solid and lumenized vascular tissue spheroids. Organ
      printing could dramatically enhance and transform the field of tissue engineering
      by enabling large-scale industrial robotic biofabrication of living human organ
      constructs with "built-in" perfusable intraorgan branched vascular tree. Thus,
      organ printing is a new emerging enabling technology paradigm which represents a
      developmental biology-inspired alternative to classic biodegradable solid
      scaffold-based approaches in tissue engineering.

PMID- 19176249
TI  - Low plasma adiponectin levels in obsessive-compulsive disorder.
AB  - This study was designed to examine plasma adiponectin levels in patients with
      obsessive-compulsive disorder (OCD). The plasma adiponectin and glucose
      concentrations were determined in 23 patients (13 females, 10 males) and age and
      sex-matched 23 healthy controls (14 females and 9 males). In measuring
      adiponectin levels, ELISA method was used. The mean adiponectin levels were
      11.1+/-2.2 ng/ml for the patient group and 17.6+/-2.9 ng/ml for control group
      (P=0.00078). By using ANCOVA, significant difference in the mean adiponectin
      values continued after controlling for BMI or sex (F=6.04, P<0.013 adjusted for
      BMI; F=5.67, P<0.021 adjusted for sex). Despite some limitations, the present
      study suggests that there may be an interaction between OCD and plasma
      adiponectin. In this interaction, one should keep into mind both pathophysiologic
      dimension and cardiovascular vulnerability. But it is clear that although the
      present findings are of considerable significance they should be supported by the
      studies with larger sample.

PMID- 19176250
TI  - Left main stem rupture caused by methicillin resistant Staphylococcus aureus
      infection of left main stent treated by covered stenting.
AB  - Coronary artery infection after angioplasty or stent implantation is a rare and
      dreaded complication of percutaneous coronary intervention. 80% of the cases are
      due to Staphylococcus aureus. About half the cases lead to rupture or perforation
      of the coronary artery while the other half presents as abscesses or aneurysms.
      Surgical treatment is the conventional therapeutic modality but it carries a high
      mortality. We report a case of a high risk patient who had methicillin resistant
      Staphylococcus aureus infection of left main stem stent leading to rupture and
      pseudoaneurysm formation that is successfully treated with stent graft.

PMID- 19176251
TI  - The reversible oral P2Y12 antagonist AZD6140 inhibits ADP-induced contractions in
      murine and human vasculature.
AB  - OBJECTIVES: The platelet ADP P2Y(12) receptor which is a target for the
      antithrombotic drug clopidogrel is also distributed on vascular smooth muscle
      cells and stimulate contraction. This study investigates whether AZD6140, in
      contrast to clopidogrel, can inhibit ADP-mediated arterial contractions. METHODS:
      Mice were treated with clopidogrel, 50 mg/kg, 24 and 2 h before experiment.
      Thoracic aorta ring segments from both clopidogrel-treated (n=5) and untreated
      (n=4) mice were mounted in myograph baths. Contractions of human left internal
      mammary arteries (IMA) and small arteries were studied in an identical manner.
      RESULTS: Clopidogrel treatment per os did not inhibit contractions by the stable
      ADP analogue 2-MeSADP (10 microM). However, addition of 1 microM AZD6140 in vitro
      inhibited ADP contraction (% of maximal contraction by 60 mM K(+)) both in the
      clopidogrel-treated, from 64% to 32% (P=0.002) and in the untreated group, from
      59% to 33% (P=0.015). 2-MeSADP contractions in human IMA and small arteries were
      inhibited by AZD6140. CONCLUSIONS: The antiplatelet drug AZD6140 blocks the
      contractile effects of ADP in both murine and human vasculature. These effects of
      AZD6140 could be beneficial in the management of conditions in which vasospasm
      may play a role.

PMID- 19176252
TI  - Epicardial cells are missing from the surface of hearts with ischemic
      cardiomyopathy: a useful clue about the self-renewal potential of the adult human
      heart?
AB  - The search for ideal cell candidate for heart regeneration, as well as for
      putative cardiac stem cell responsible for cardiac tissue homeostasis, is
      occupying both basic scientists and clinicians. Growing number of studies and
      publications indicate epicardium-derived cells as cardiac stem cells. While it is
      beyond doubt that these cells contribute to normal development of the heart
      during organogenesis, it remains an open question whether mesothelial epicardial
      cells can preserve their embryonic potential and if they can undergo epithelial
      mesenchymal transition, giving origin to cardiac cell lineages, also in the adult
      human heart. Recent observations in vitro confirm this hypothesis, but direct
      evidence from the adult human heart is difficult to obtain. We report the absence
      of epicardial cells from the surface of adult human hearts with ischemic
      cardiomyopathy and the accumulation of cells with epithelial and mesenchymal
      markers in the subepicardium. We argue that these findings may correspond to the
      activation of the epithelial-mesenchymal transition in the chronic pathological
      conditions requiring cardiac cell regeneration, followed by epicardial cell pool
      exhaustion. Hence, observation of the epicardium of patients with cardiovascular
      disease, although not offering immediate diagnostic advantage, could provide some
      urging answers concerning the self-renewal potential of the adult heart.

PMID- 19176253
TI  - Honey intoxication and the Bezold-Jarisch reflex.
AB  - Food-poisonings with grayanotoxin-contaminated honey can induce atrioventricular
      blocks. Actually, grayanotoxin and similar neurotoxins like veratridine stimulate
      the unmyelinated afferent cardiac branches of the vagus nerve. Tonic inhibition
      of central vasomotor centres leads to a reduced sympathetic output and a reduced
      peripheral vascular resistance with bradycardia, continued hypotension, and
      peripheral vasodilation. This cardioinhibitory reflex is known as the Bezold
      Jarisch reflex. Recognition of the Bezold-Jarisch reflex is important, as there
      is no need for electric pacing, when atrioventricular blocks occur. The
      pharmacologically induced bradycardia and heart blocks do promptly disappear
      after injection of the antidote atropine.

PMID- 19176254
TI  - Exercise-induced ST-segment depression in inferior leads during treadmill
      exercise testing and coronary artery disease.
AB  - The exercise electrocardiogram is a commonly used non-invasive and inexpensive
      method for detection of electrocardiogram (ECG) changes secondary to myocardial
      ischemia. Reversible ST-segment depression is the characteristic finding
      associated with exercise-induced, demand-driven ischemia in patients with
      significant coronary obstruction but no flow limitation at rest. The exercise
      induced ST-segment depression in inferior leads has been questioned and it has
      been reported that lead V5 alone consistently outperforms the inferior leads and
      the combination of lead V5 with II, because lead II has a high false-positive
      rate. A review of the 12-lead visual electrocardiographic interpretations
      confirmed that changes isolated to the inferior leads were rare in patients, who
      had no diagnostic Q waves. Considering the sum of ST-segment depression or the
      most depression in the three leads representing the three main areas of the
      myocardium (II, V2, and V5) did not improve the diagnostic capacity of the test.
      A case is presented to illustrate how in a patient, the ST-segment depression in
      inferior leads during exercise testing is related with significant coronary
      artery disease. We present a case of exercise-induced ST-segment depression in
      inferior leads in a 52 year-old Italian man. This experience demonstrates that ST
      segment depression in inferior leads during the exercise testing can have a
      diagnostic significance.

PMID- 19176255
TI  - The small intestine: a critical linkage in pathophysiology of cardiac cachexia.
AB  - Impaired functioning of the gastrointestinal system may also contribute to
      malnutrition and cardiac cachexia (CC) in patients with chronic heart failure
      (CHF). Targets for future interventions include the deranged hormonal systems
      involved in energy balance as well as malabsorption from the gut and dietary
      supplementation. Other targets are the inhibition of proteasome-dependent protein
      degradation and the direct inhibition of pro-inflammatory pathways. The
      beneficial effects of ACE inhibitors, aldesterone inhibitors and beta-blockers in
      preventing or delaying the collagen deposition in the small intestine wall need
      to be elucidated. We strongly believe that by improving our understanding of the
      role of the gut in CC will lead to the development of novel therapeutic
      strategies in the near future.

PMID- 19176256
TI  - Hyperoxic chemoreflex sensitivity is impaired in patients with neurocardiogenic
      syncope.
AB  - BACKGROUND: During the development of neurocardiogenic syncope (NCS) postural
      dependant venous blood pooling sets off a cascade of autonomic reflexes. This
      causes an initial rise in sympathetic tone, which is followed by an overshoot
      parasympathetic activation resulting in systemic vasodilatation and/or sinus
      bradycardia. However, other factors like associated hyperventilation or changes
      in blood gas content may also contribute to syncope. Hyperoxic cardiac
      chemoreflex sensitivity (CHRS) is an autonomic functional test that describes the
      heart rate decrease in response to increases in blood oxygen content. The purpose
      of this study was to investigate whether CHRS is altered in NCS. METHODS AND
      RESULTS: CHRS was compared in 16 NCS patients (49+/-4 yr old) vs. 16 age and
      gender matched controls (53+/-2 yr old). NCS was verified by clinical syncope and
      positive head-up tilt testing. The hyperoxic CHRS was measured by determination
      of the venous partial pressure of oxygen and heart rate before and after 5 min of
      pure oxygen inhalation. The difference of the R-R intervals before and after
      oxygen inhalation divided by the difference in the oxygen pressures were
      calculated as hyperoxic chemoreflex sensitivity [ms/mm Hg]. CHRS in the control
      group was 7.1+/-1.1 ms/mm Hg. By contrast, CHRS in NCS patients was significantly
      lower (2.8+/-1.0 ms/mm Hg; p<0.05). CONCLUSION: Neurocardiogenic syncope is
      associated with decreased hyperoxic cardiac chemoreflex sensitivity possibly
      reflecting impaired deactivation of arterial chemoreceptors. The clinical and
      pathophysiologic importance of chemosensor function in neurocardiogenic syncope
      needs to be investigated in more detail.

PMID- 19176257
TI  - Can leukocyte telomere length (LTL) be considered as an index in application of
      neural network in the atherosclerosis risk stratification?

PMID- 19176258
TI  - Short-term changes in circulating insulin and free fatty acids affect Nt-pro-BNP
      levels in heart failure patients.

PMID- 19176259
TI  - Shock wave therapy of ischemic heart disease in the light of general pathology.

PMID- 19176260
TI  - High plasma adiponectin is related to low functional capacity in patients with
      chronic heart failure.
AB  - We evaluated the association between plasma adiponectin and functional capacity
      in patients with chronic heart failure (CHF). Similarly to NT-proBNP, plasma
      adiponectin was elevated in CHF compared to healthy controls. Adiponectin
      correlated inversely with peak oxygen consumption and 6-minute walking distance
      and was able to identify CHF patients with impaired exercise capacity. Our
      findings support a role of adiponectin as an index of heart failure severity.

PMID- 19176261
TI  - Heart rate variability predicts outcome in children with pulmonary arterial
      hypertension.
AB  - INTRODUCTION: Objective risk stratifiers are required to assess need for
      escalation of medical therapy or listing for transplantation in children with
      pulmonary arterial hypertension (PAH). We aimed to assess whether heart rate
      variability (HRV) predicts outcome in children with severe PAH. PATIENTS AND
      METHODS: Parameters of HRV [SDNN = standard deviation of normal-to-normal
      intervals, SDANN = standard deviation of mean values for normal-to-normal
      intervals over 5 min, and RMSSD = square root of the mean square differences of
      successive RR intervals] were determined from Holter electrocardiograms of 47
      patients (27 male; mean age 11.4+/-5.5 years) with PAH (idiopathic PAH n=21;
      associated PAH n=26). HRV was assessed in relation to WHO Functional Class, six
      minute-walk-test, echocardiographic and haemodynamic data, and as a predictor of
      death or lung transplantation. RESULTS: The mean follow-up period was 19+/-11.5
      months (1.8-49.1 months). Ten patients died and 7 underwent transplantation and
      these children had significantly lower values of HRV [SDANN (70.7+/-30.9 vs.
      119.2+/-57.2), SDNN (79.5+/-30.5 vs. 129.9+/-63.6), and RMSSD (22.+/-11.7 vs.
      47.7+/-34.5); p<0.001 for all]. On univariate Cox-proportional-hazards analysis
      all parameters of HRV predicted death or transplantation (p<0.05). SDANN and SDNN
      were also predictive of mortality alone (p<0.05). On bivariate analysis SDANN and
      SDNN predicted outcome independently of functional status, syncope, right
      ventricular function, and haemodynamic parameters. CONCLUSIONS: HRV is a useful,
      non-invasive means of predicting a poor outcome and hence need to escalate
      therapy in children with PAH.

PMID- 19176262
TI  - Benefit of prostaglandin infusion in severe heart failure: preliminary clinical
      experience of repetitive administration.
AB  - BACKGROUND: Prostaglandin E1 (PGE1) is a potent vasodilating drug, which has been
      used in treatment of primary pulmonary hypertension. However intravenous PGE1
      infusion may be of benefit and also has been proposed as a therapeutic tool in
      patients with end-stage heart failure. The aim of this prospective not randomized
      study was to assess the clinical and instrumental effects of this agent in
      patients with severe heart failure and pulmonary hypertension. METHODS: To
      investigate the effects of PGE1 in congestive heart failure we selected 22
      consecutive patients (16 males, 6 females, mean age 63+/-2 years) in the mean
      NYHA class III, because they had pulmonary hypertension (PAPs>3 m/s and left
      ventricular ejection fraction (LVEF) <=35% by echocardiography. A control group
      of 23 patients (19M, 4F mean age 62+/-5 years; 9 patients were in the NYHA class
      IV and 14 in the NYHA class III), with the same instrumental and clinical data,
      received an optimized oral treatment with beta-blockers, ACE-inhibitors,
      furosemide and digitalis. Right heart catheterization was performed to confirm
      and determine the type of pulmonary hypertension, before starting the PGE1
      infusion. Clinical and echocardiography evaluation was performed during follow
      up. PGE1 was infused at a mean dose of 10 ng/kg/min for a total of 24 h over
      three consecutive days every three months. RESULTS: Right heart catheterization
      confirmed a high systolic pulmonary pressure in all patients; pre-capillary
      pulmonary hypertension (mean PAP>25 mm/Hg) was 25%. During a mean follow-up of
      36+/-6 months, 16 patients died (10 in the control group and 6 in the PGE1
      group). The Kaplan-Meier 3-years survival analysis was not statistically
      significant (Log-rank test), but at 2 months survival rates began to diverge; 36
      months survival: 72.7% in the PGE1 group and 56% in the control group. The mean
      LVEF increased from 25.78% to 32.1% in the PGE1 group and from 23.38% to 26.15 in
      the control group (p<0.001); the NYHA mean class improved from 3.18 to 2.24 in
      the PGE1 group and from 3.46 to 3.38 in the control group (p<0.05). The PAP
      decreased from 57.65 to 40.82 mm/Hg (p<0.001). An AICD was implanted in 3
      patients in the first group and in 5 patients in the control group. Two patients
      were added to the heart transplantation list. CONCLUSION: These preliminary data
      suggest that intermittent PGE1 infusion in patients with advanced congestive
      heart failure and high pulmonary pressure is able to improve NYHA mean class
      (p<0.05), ventricular contractility (LVEF p<0.001), pulmonary pressure and
      clinical data. It hasn't been associated to morbid events or increased risk of
      death.

PMID- 19176263
TI  - Short-term walking physical training and changes in body hydration status, B-type
      natriuretic peptide and C-reactive protein levels in compensated congestive heart
      failure.

PMID- 19176264
TI  - De pulsibus--or sense and simplicity in daily medical practice.
AB  - In today's medicine ultrasound and imaging are dominant features. As a
      consequence a tactile maneuver like palpation of the pulse became something like
      a relic from the past, rather trivial and habitual but certainly not an activity
      to be haughty about in terms of skill and professional development. Nevertheless
      medical history tells a complete different story and rehabilitation of the pulse
      lore is highly desirable as a tool with sense and simplicity, reassuring when
      possible but for all as an inexpensive and accessible instrument with a
      substantial diagnostic yield.

PMID- 19176265
TI  - Facing the problem of "false positives": re-assessment and improvement of a
      multiplex RT-PCR procedure for the diagnosis of A. flavus mycotoxin producers.
AB  - The aim of our research project was to consolidate a multiplex RT-PCR protocol to
      detect aflatoxigenic strains of Aspergillus flavus. Several independent A. flavus
      strains were isolated from corn and flour samples from the North of Italy and
      from three European countries. Aflatoxin producing/not producing phenotype was
      assessed by qualitative and quantitative assays at day five of growth in
      aflatoxin inducing conditions. Expression of 16 genes belonging to the aflatoxin
      cluster was assayed by multiplex or monomeric RT-PCR. There is a good correlation
      between gene expression and aflatoxin production. Strains that apparently
      transcribed all the relevant genes but did not release aflatoxin in the medium
      ("false positives") were re-assessed for mycotoxin production after extended
      growth in inducing condition. All the "false positive" strains in actual fact
      were positive when aflatoxin determination was performed after 10 days of growth.
      These strains should then be re-classified as "slow aflatoxin accumulators". To
      optimise the diagnostic procedure, a quintuplex RT-PCR procedure was designed
      consisting of a primer set directed against four informative aflatoxin cluster
      genes and the beta-tubulin gene as an internal amplification control. In
      conclusion we have provided evidence for the robustness and reliability of our RT
      PCR protocol in discriminating mycotoxin producer from non-producer strains of A.
      flavus. and the molecular procedure we devised is a promising tool with which to
      screen and control the endemic population of A. flavus colonising different areas
      of the World.

PMID- 19176266
TI  - Dense non-aqueous phase liquids at former manufactured gas plants: challenges to
      modeling and remediation.
AB  - The remediation of dense non-aqueous phase liquids (DNAPLs) in porous media
      continues to be one of the most challenging problems facing environmental
      scientists and engineers. Of all the environmentally relevant DNAPLs, tars in the
      subsurface at former manufactured gas plants (FMGPs) pose one of the biggest
      challenges due to their complex chemical composition and tendency to alter
      wettability. To further our understanding of these complex materials, we
      consulted historic documentation to evaluate the impact of gas manufacturing on
      the composition and physicochemical nature of the resulting tars. In the recent
      literature, most work to date has been focused in a relatively narrow portion of
      the expected range of tar materials, which has yielded a bias toward samples of
      relatively low viscosity and density. In this work, we consider the dissolution
      and movement of tars in the subsurface, models used to predict these phenomena,
      and approaches used for remediation. We also explore the open issues and detail
      important gaps in our fundamental understanding of these extraordinarily complex
      systems that must be resolved to reach a mature level of understanding.

PMID- 19176267
TI  - Fractionation of radionuclide species in the environment.
AB  - Naturally occurring and artificially produced radionuclides in the environment
      may be present in different physico-chemical forms (i.e., radionuclide species)
      varying in size (nominal molecular mass), charge properties and valence,
      oxidation state, structure and morphology, density, degree of complexation, etc.
      Low molecular mass (LMM) species are believed to be mobile and potentially
      bioavailable, while high molecular mass (HMM) species such as colloids, polymers,
      pseudocolloids and particles are considered inert. Due to time-dependent
      transformation processes such as mobilisation of radionuclide species from solid
      phases or interactions of mobile and reactive radionuclide species with
      components in soils and sediments, the original distribution of radionuclides
      deposited in ecosystems will change over time. To assess the environmental impact
      from radionuclide contamination, information on radionuclide species deposited,
      interactions within affected ecosystems and the time-dependent distribution of
      radionuclide species influencing mobility and biological uptake is essential. The
      development of speciation techniques to characterize radionuclide species in
      waters, soils and sediments should therefore be essential for improving the
      prediction power of impact and risk assessment models. The present paper reviews
      available fractionation techniques which can be utilised for radionuclide
      speciation purposes.

PMID- 19176268
TI  - 239,240Pu/137Cs ratios in the water column of the North Pacific: a proxy of
      biogeochemical processes.
AB  - Anthropogenic radionuclides in seawater have been used as transient tracers of
      processes in the marine environment. Especially, plutonium in seawater is
      considered to be a valuable tracer of biogeochemical processes due to its
      particle-reactive properties. However, its behavior in the ocean is also affected
      by physical processes such as advection, mixing and diffusion. Here we introduce
      Pu/(137)Cs ratio as a proxy of biogeochemical processes and discuss its trends in
      the water column of the North Pacific Ocean. We observed that the
      (239,240)Pu/(137)Cs ratio in seawater exponentially increased with increasing
      depth (depth range: 100-1000 m). This finding suggests that the profiles of the
      (239,240)Pu/(137)Cs ratios in shallower waters directly reflect biogeochemical
      processes in the water column. A half-regeneration depth deduced from the curve
      fitting the observed data, showed latitudinal and longitudinal distributions,
      also related to biogeochemical processes in the water column.

PMID- 19176269
TI  - Length of life inequality around the globe.
AB  - Inequality in the distribution of adult length of life - defined as age at death
      in the population aged 15 and over - is studied for virtually all countries of
      the world using a new database with over 9000 life tables covering a period of up
      to two centuries. The data reveal huge variation among countries and time periods
      in the degree to which the available years of life are distributed equally among
      the population. Most length of life inequality (about 90%) is within-country
      inequality. Our findings make clear that measures of length of life inequality
      should be adjusted for life expectancy to get a more relevant indicator of length
      of life differentials across populations. At similar levels of life expectancy,
      substantial differences in inequality are observed, even among highly developed
      countries. Expressed as premature mortality, inequality may be 35-70% higher in
      the most unequal countries compared to the most equal ones. Countries that
      reached a certain level of life expectancy earlier in time than other countries,
      and countries that improved their life expectancy more quickly than others,
      experienced higher levels of inequality.

PMID- 19176270
TI  - Dynamic conformational changes due to the ATP hydrolysis in the motor domain of
      myosin: 10-ns molecular dynamics simulations.
AB  - Muscle contraction is caused by directed movement of myosin heads along actin
      filaments. This movement is triggered by ATP hydrolysis, which occurs within the
      motor domain of myosin. The mechanism for this intramolecular process remains
      unknown owing to a lack of ways to observe the detailed motions of each atom in
      the myosin molecule. We carried out 10-ns all-atom molecular dynamics simulations
      to investigate the types of dynamic conformational changes produced in the motor
      domain by the energy released from ATP hydrolysis. The results revealed that the
      thermal fluctuations modulated by perturbation of ATP hydrolysis are biased in
      one direction that is relevant to directed movement of the myosin head along the
      actin filament.

PMID- 19176271
TI  - Experimenting and daily smokers: episodic patterns of alcohol and cigarette use.
AB  - Alcohol use may facilitate the development of nicotine dependence. Alcohol is
      often paired with cigarette smoking, particularly in those experimenting with
      smoking. However, little research has examined episodic patterns of alcohol and
      cigarette use. This study examined patterns of alcohol and cigarette use in a
      college-aged sample (n=237) designated as experimenters or smokers based on their
      smoking history. Participants reported their consumption of drinks and cigarettes
      by hour, for each hour, of a typical drinking and smoking episode. Self-reported
      pleasure and desire associated with smoking generally and while drinking was
      assessed. No group difference was observed in total number of drinks. However,
      experimenters delayed smoking until more drinks were consumed, suggesting they
      smoked after reaching binge levels of alcohol. By contrast, smokers smoked after
      fewer drinks. Both groups reported increased smoking while drinking and increased
      pleasure and desire when smoking while drinking. The increase was greater in
      experimenters. Concurrent alcohol and cigarette use may facilitate the
      development of tobacco dependence and interventions interrupting their pairing
      might impede the transition from experimenter to smoker.

PMID- 19176272
TI  - Recognizing false biochemical failure calls after radiation with or without neo
      adjuvant androgen deprivation for prostate cancer.
AB  - PURPOSE: We studied prostate-specific antigen (PSA) changes after radiation with
      or without neoadjuvant androgen deprivation to determine posttreatment PSA
      scenarios in which false-positive biochemical failures (FPBF) are most likely to
      occur. METHODS AND MATERIALS: In the Trans-Tasman Radiation Oncology 96.01 Group
      trial, patients with T2b, 2c, 3, 4 N0 prostate cancer were randomized to 3 or 6
      months goserelin and flutamide (STAD) before and during 66 Gy to the prostate and
      seminal vesicles (XRT) or to XRT alone. Piecewise longitudinal changes in PSA
      before relapse were characterized and quantified to determine which might cause
      FPBF calls. RESULTS: Between 1996 and 2000, 802 eligible patients were
      randomized. Of these, 492 met the criteria for American Society for Therapeutic
      Radiology and Oncology (ASTRO) failure and 467 for Phoenix failure. Seventy-seven
      ASTRO fails and 39 Phoenix fails were deemed false positives (FPs). The majority
      of FPBFs were associated with the "plateauing" in PSA values that follow
      posttreatment nadir. FPBFs were particularly common in men treated with STAD, in
      whom small, consecutive PSA rises before or during this phenomenon triggered 56
      FP ASTRO fail calls. In these men, the Phoenix fail criteria triggered only 15
      FPBF calls. However, the Phoenix criteria were more vulnerable than ASTRO to
      short-term isolated PSA rises during plateau, which resulted in 15 Phoenix fail
      calls but only 3 FP ASTRO fails. CONCLUSIONS: The Phoenix definition avoided 50%
      of FPBF calls that occurred with the ASTRO definition. Failures should be
      confirmed by further PSA rises before investigation and treatment is considered.

PMID- 19176273
TI  - Gram staining: an unexplored diagnostic tool for diagnosis of meningococcal
      infection in the developing world.

PMID- 19176274
TI  - Extensive soft tissue resection with autologous tissue closure for locally
      recurrent breast cancer: lasting local control and acceptable morbidity.
AB  - INTRODUCTION: Locoregional breast cancer recurrence can be detected at an
      advanced stage of the disease. To achieve local control for these larger local
      breast cancer recurrences, wide soft tissue resections with autologous tissue
      coverage of the defect is an option. The aim of this study was to assess the
      local control and morbidity of surgical salvage of patients with advanced local
      breast cancer recurrence using autologous tissue closure of the defect. MATERIAL
      AND METHODS: Eighty-eight patients were treated with wide soft tissue resections
      with autologous tissue coverage from 1993 to 2006. Two different operating
      techniques were used for closure of the defect; transposition of the greater
      omentum covered with split skin graft and the latissimus dorsi musculo-cutaneous
      flap. Demographic, treatment and mortality information were retrieved from
      original patients' files. RESULTS: Postoperatively 10 patients (11%) developed
      complications which required an additional operation. In patients treated with
      curative intent (n=67) median disease-free interval after extensive surgery was
      24 months and median survival was 45 months. In 42 patients (47% of all included
      patients) the first recurrence after extensive surgery was a locoregional
      relapse. The two surgical techniques did not differ in overall survival (p=0.739)
      and local control. CONCLUSION: Large soft tissue resection for extensive local
      relapse of breast cancer may result in lasting local control in half of the
      patients with acceptable morbidity.

PMID- 19176275
TI  - A randomized controlled trial of group cognitive-behavioral therapy vs. enhanced
      supportive therapy for auditory hallucinations.
AB  - There has been little research examining group cognitive-behavioral therapy (CBT)
      for schizophrenia, especially compared to an active control treatment. The
      purpose of this study was to investigate the effectiveness of group CBT for
      auditory hallucinations compared to an enhanced supportive therapy (ST). Sixty
      five participants with schizophrenia spectrum disorders and persistent
      hallucinations were randomly assigned to group CBT or enhanced group ST. Primary
      outcomes focused on beliefs about voices and global auditory hallucinations
      severity. Secondary outcomes included psychotic symptoms, self-esteem, social
      functioning, insight, depression, and hospitalization. Controlling for baseline
      levels, these outcomes were evaluated across post-treatment, 3 month and 12 month
      follow-ups. Participants who received enhanced ST were less likely to both resist
      voices and to rate them as less malevolent through 12-month follow-up relative to
      participants who received CBT. Group CBT was associated with lower general and
      total symptom scores on the PANSS through 12-month-followup relative to
      participants who received enhanced ST. Outcomes improved through 12-month follow
      up in both therapy groups, with enhanced ST having more specific impact on
      auditory hallucinations, and CBT impacting general psychotic symptoms.

PMID- 19176276
TI  - Risk factors for suicide in schizophrenia: findings from a Swedish population
      based case-control study.
AB  - Previous reports regarding risk factors for suicide in schizophrenia have been
      inconclusive. We performed a matched case-control study of in-patient-treated
      schizophrenia patients in order to assess the suicide risk associated with
      socioeconomic, demographic, and psychiatric factors. The cases were 84 patients
      who died by suicide within five years after diagnosis in a cohort of all patients
      discharged for the first time from psychiatric hospitals in Stockholm County,
      Sweden, with a diagnosis of schizophrenia, schizophreniform disorder or
      schizoaffective disorder between the years 1984 and 2000. One control was
      individually and randomly matched with each case from the same cohort by date (+/
      1 year) and age (+/-5 years) at index diagnosis. Data were retrieved from
      clinical records of the case-control pairs in a blind fashion. Of the suicides,
      54% were men and 46% were women. In multivariate analyses, higher educational
      attainment (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.03-8.0), age
      >or=30 years at onset of symptoms (OR 4.8, CI 1.1-21.2), and a history of a
      suicide attempt requiring non-psychiatric medical treatment (OR 5.0, CI 1.6-15.4)
      were found to be significantly associated with an increased suicide risk. Gender
      did not significantly affect the suicide risk, nor did a history of self
      discharge, compulsory in-patient treatment, substance-use disorder or a family
      history of mental disorders or suicide. In schizophrenia, certain suicide risk
      factors may differ from those in the general population. Clinical suicide risk
      assessment for schizophrenia patients should be performed taking this into
      account.

PMID- 19176277
TI  - Repeated electroconvulsive seizures increase the total number of synapses in
      adult male rat hippocampus.
AB  - The underlying mechanism of the therapeutic effect of electroconvulsive therapy
      (ECT) is still unclear. Here we investigated whether repeated electroconvulsive
      seizures (ECS), an animal model of ECT, in rats induce neuroplastic changes in
      the subregions of the hippocampus. ECS or sham treatment was given daily for 10
      days to adult male rats. Stereological principles were employed to quantify
      volumes and the number of neurons and synapses. Volumes of granule cell layer
      (GCL) and Hilus in Dentate Gyrus of the hippocampus were significantly larger in
      the ECS treatment group. The neuron numbers in GCL, synapse numbers (including
      total synapses, spine synapses, and both perforated and nonperforated spine
      synapse subtypes) and synapse height in CA1 were significantly increased in the
      ECS treatment group. Our results indicated that repeated ECS induces
      neurogenesis, synaptogenesis and remodelling of synapses in rat hippocampus. This
      could provide a potential mechanism to explain the therapeutic effect of ECS.

PMID- 19176278
TI  - Caudate volumes in public transportation workers exposed to trauma in the
      Stockholm train system.
AB  - The caudate nucleus is a structure implicated in the neural circuitry of
      psychological responses to trauma. This study aimed to quantify the volume of the
      caudate in persons exposed to trauma. Thirty-six subjects under 65 were recruited
      from transport workers in Stockholm who reported having been unintentionally
      responsible for a person-under-the-train accident or among employees having
      experienced an assault in their work (1999-2001) between 3 months and 6 years
      before MRI scanning. In those exposed to the trauma, a DSM-IV diagnosis of post
      traumatic stress disorder (PTSD) was made by an independent psychiatrist, with
      subjects being classified as PTSD or no PTSD. MRI data were analyzed blindly to
      all clinical information by an experienced rater using a standardized manual
      tracing protocol to quantify the volume of the caudate. Within-group comparisons
      of PTSD (n=19) and no PTSD (n=17) found the right caudate nucleus to be
      significantly (9%) larger than the left: a right hemisphere baseline asymmetry. A
      multivariate analysis of covariance (MANCOVA) was conducted to assess the volume
      of the caudate nucleus (right and left) in relation to the diagnosis of no PTSD
      (n=17) or PTSD (n=19). After adjustment for the covariates (age, sex,
      intracranial volume, years since trauma, and number of trauma episodes), there
      was a significant difference in raw right caudate nucleus volume between subjects
      with PTSD compared with those without PTSD. Volume of the left caudate nucleus
      was not significantly different between the PTSD and no PTSD groups. The right
      caudate volume in the PTSD group was 9% greater compared with the no PTSD group.
      There is a larger right hemisphere volume of the caudate within those exposed to
      trauma with active PTSD compared with those without PTSD, superimposed upon a
      baseline caudate asymmetry.

PMID- 19176279
TI  - Cortico-limbic response to personally challenging emotional stimuli after
      complete recovery from depression.
AB  - People vulnerable to depression are at increased risk of relapse if they live in
      highly critical family environments. To explore this link, we used neuroimaging
      methods to examine cortico-limbic responding to personal criticisms in healthy
      participants and participants with known vulnerability to major depression.
      Healthy controls and fully recovered participants with a past history of major
      depression were scanned while they heard praising, critical, and neutral comments
      from their own mothers. Prior to scanning, the formerly depressed and the control
      participants were indistinguishable with respect to self-reported positive,
      negative, or anxious mood. They also reported similar mood changes after being
      praised or criticized. However, formerly depressed participants responded to
      criticism with greater activation in the amygdala and less activation in the
      dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) than
      did controls. During praise and neutral commentary, amygdala activation was
      comparable in both groups, although lower levels of activation in the DLPFC and
      ACC still characterized formerly depressed participants. Vulnerability to
      depression may be associated with abnormalities in cortico-limbic activation that
      are independent of mood state and that remain even after full recovery. Criticism
      may be a risk factor for relapse because it activates the amygdala and perturbs
      the affective circuitry that underlies depression.

PMID- 19176280
TI  - Neural correlates of episodic and semantic memory retrieval in borderline
      personality disorder: an fMRI study.
AB  - Verbal memory impairment in borderline personality disorder (BPD) is still a
      matter of debate. In this study we combine investigations of both, memory
      retrieval as well as underlying neural circuits in BPD. Functional magnetic
      resonance imaging (fMRI) was used to study regional brain activation in 18 right
      handed female patients with BPD and 18 matched controls during the retrieval of
      an episodic memory retrieval (EMR) task (free recall of a word list) and a
      semantic memory retrieval (SMR) task (verbal fluency). Despite unaffected
      performance in EMR and SMR, patients with BPD showed task-specific increased
      activation compared with controls. During EMR, the increased activation
      encompassed the posterior cingulate cortex bilaterally, the left middle and
      superior temporal gyrus, the right inferior frontal gyrus, and the right angular
      gyrus. SMR was associated with increased activation of the posterior cingulate
      cortex, of the right fusiform gyrus, of the left anterior cingulate cortex, and
      of the left postcentral gyrus. Our findings suggest that BPD patients may need to
      engage larger brain areas to reach a level of performance in episodic and
      semantic retrieval tasks that is comparable to that of healthy controls.

PMID- 19176281
TI  - Dopamine transporter imaging in adult patients with attention
      deficit/hyperactivity disorder.
AB  - The aim of this study was to provide in vivo evidence for the hypothesis that
      dopaminergic neurotransmission is altered in adult patients with attention
      deficit/hyperactivity disorder (ADHD). We used high-resolution brain-dedicated
      single-photon emission computed tomography and the dopamine transporter (DAT)
      marker [(123)I]FP-CIT in 17 adult treatment-naive ADHD patients and 14 age
      matched controls. Magnetic resonance imaging-based region of interest analysis
      was performed to quantify the DAT availability (expressed as a ratio of specific
      to non-displaceable binding, V(3)'') in the striatum. Additionally, the specific
      radiotracer binding was assessed in the thalamus and the midbrain/brainstem
      regions (reflecting also the availability of the serotonin transporter to which
      [(123)I]FP-CIT binds with moderate affinity). In the striatal areas of the ADHD
      patients, a significantly reduced specific tracer binding was found (V(3)'':
      5.18+/-0.98; controls 6.36+/-1.34). In contrast, the specific [(123)I]FP-CIT
      binding did not differ from controls in the thalamus and midbrain/brainstem
      areas. These data indicate a reduced dopaminergic but not serotonergic
      transmitter reuptake function in adult ADHD. Further studies will have to deal
      with the question of whether these findings have the potential to influence
      treatment decisions in this complex disorder.

PMID- 19176282
TI  - Adherence to the Mediterranean diet and risk of metabolic syndrome and its
      components.
AB  - BACKGROUND AND AIMS: The role of diet in the aetiology of metabolic syndrome
      (MetS) is not well understood. The aim of the present study was to evaluate the
      relationship between adherence to the Mediterranean diet (MedDiet) and MetS.
      METHODS AND RESULTS: A cross-sectional study was conducted with 808 high
      cardiovascular risk participants of the Reus PREDIMED Centre. MetS was defined by
      the updated National Cholesterol and Education Program Adult Treatment Panel III
      criteria. An inverse association between quartiles of adherence to the MedDiet
      (14-point score) and the prevalence of MetS (P for trend<0.001) was observed.
      After adjusting for age, sex, total energy intake, smoking status and physical
      activity, participants with the highest score of adherence to the MedDiet (>/=9
      points) had the lowest odds ratio of having MetS (OR [95% CI] of 0.44 [0.27
      0.70]) compared to those in the lowest quartile. Participants with the highest
      MedDiet adherence had 47 and 54% lower odds of having low HDL-c and
      hypertriglyceridemia MetS criteria, respectively, than those in the lowest
      quartile. Some components of the MedDiet, such as olive oil, legumes and red wine
      were associated with lower prevalence of MetS. CONCLUSION: Higher adherence to a
      Mediterranean diet is associated with a significantly lower odds ratio of having
      MetS in a population with a high risk of cardiovascular disease.

PMID- 19176283
TI  - Prevalence of obesity and physical inactivity among farmers from Crete (Greece),
      four decades after the Seven Countries Study.
AB  - BACKGROUND AND AIM: As first shown 40 years ago farmers from Crete had one of the
      healthiest lifestyles compared to other participants of the Seven Countries
      Study. Taking the above into account we investigated the prevalence of obesity
      and its indexes among farmers in Crete in 2005. METHODS AND RESULTS: 502 farmers
      (18-79 years old) from the Valley of Messara in Crete were randomly selected and
      examined. Body Mass Index (BMI), waist circumference (WC), waist-to-hip ratio
      (W/Hip Ratio), waist-to-height ratio (W/Height Ratio), conicity index, percentage
      of body fat and hours of daily light physical activity (LPhA) and moderate-to
      vigorous physical activity (MVPhA) were calculated for each subject. 86,1% of the
      study population was overweight and/or obese. Specifically 42.9% had a BMI of
      25.1-30 kg/m(2) and were overweight and 43.2% were obese with a BMI>30 kg/m(2).
      The percentage of body fat was estimated at 27.3% of total body weight among
      males and 39.3% among females, while all obesity indexes were found to differ
      between genders. CONCLUSIONS: In comparison to middle aged male farmers from
      Crete in the 1960s, mean weight has increased by 20 kg (83 kg vs. 63 kg), which
      has lead to a 7 kg/m(2) in mean BMI (22.9 kg/m(2) vs. 29.8 kg/m(2)), findings
      that support the fact that the prevalence of obesity in Greece has risen
      dramatically over the years, even among farmers from Crete, a population
      historically known for being the gold standard of health status globally.

PMID- 19176284
TI  - IL-18 gene polymorphism and metabolic syndrome.

PMID- 19176285
TI  - Case report: the nest technique for management of a periprosthetic patellar
      fracture with severe bone loss.
AB  - Periprosthetic patellar fracture with marked loss of bone stock presents a
      significant problem in total knee arthroplasty. Treatment outcomes are often
      unsatisfying and may lead to disruption of the extensor mechanism of the knee. We
      present a patient with a Type IIIb periprosthetic patellar fracture treated by a
      novel approach. Three Steinmann pins were used to reduce the patella and form
      scaffold for bone graft and a patellar button was cemented into the construct. At
      7 years followup, the patient has maintained excellent range of motion, reports
      no knee pain, has healed the patella fracture, and has restored patellar bone
      stock.

PMID- 19176286
TI  - Diabetes mellitus and hypertension as risk factors for early diffuse idiopathic
      skeletal hyperostosis (DISH).
AB  - OBJECTIVES: To describe and identify factors, in clinical practice, that might be
      useful increasing the index of suspicion for diffuse idiopathic skeletal
      hyperostosis (DISH), at a relatively young age. DESIGN: A group of 18 patients
      with DISH (12.8) who were diagnosed before the age of 50 years (group A) was
      compare with a group of 20 patients of similar age with osteoarthritis (group B),
      and 24 patients with DISH diagnosed after the age of 60 years (group C). Data
      collection included demographic characteristics, body region of main complaint
      evidence for enthesopathies or tendonitis, length of follow-up, body mass index
      (BMI), serum lipid profile, family history of diabetes mellitus (DM), and
      hypertension (HTS). The presence of concomitant diseases and use of medications
      was recorded at presentation and during the follow-up period. RESULTS: Patients
      in group A compared with group B, had statistically significant more pain in the
      lumbar and thoracic spine (P=0.001 and 0.016, respectively),
      tendonitis/enthesopathies (P=0.004), obesity (BMI> or =30, P=0.014), and first
      degree relative with HTS and DM (P=0.015 and 0.05, respectively). By the end of
      the follow-up, significantly more patients in group A were affected by DM
      compared with group B (P=0.007). CONCLUSIONS: Individuals in the fifth decade of
      life are likely to be affected by DISH if they are obese, have a first degree
      relative with either HTS or DM, complain of lumbar or thoracic spinal pain, and
      are affected by enthesopathies or tendonitis. The likelihood of relatively young
      patients with > or =3 clinical parameters to be affected with DISH, was six times
      higher than age and sex matched controls (P=0.004).

PMID- 19176287
TI  - Heme carrier protein 1 (HCP1) genetic variants in the Hemochromatosis and Iron
      Overload Screening (HEIRS) Study participants.
AB  - Heme carrier protein 1 (HCP1) has been identified as a possible heme carrier by
      in vitro analysis. To determine the association of mutations within the HCP1 gene
      with iron phenotypes, we examined the entire coding region of the HCP1 gene in
      788 US and Canadian participants selected from the Hemochromatosis and Iron
      Overload Screening (HEIRS) Study using denaturing high-performance liquid
      chromatography. We sequenced the exon and flanking intronic regions if variants
      were detected. We tested 298 non-C282Y homozygotes from four racial/ethnic
      backgrounds (White, Black, Asian, and Hispanic) selected because they had high
      serum ferritin (SF) and transferrin saturations (TS). As controls, we chose 300
      other random participants of the same racial/ethnic backgrounds from the same
      geographic locations. From the 333 HEIRS Study C282Y homozygotes, we selected 75
      based on high SF and TS, 75 based on low SF and TS; and 75 were selected randomly
      as controls. Thirty-five of the randomly selected C282Y homozygotes were also
      included in the high and the low SF and TS groups due to numerical limitations.
      We identified eight different HCP1 genetic variants; each occurred in a
      heterozygous state. Except one, each was found in a single HEIRS Study
      participant. Thus, HCP1 variants are infrequent in the populations that we
      tested. Five HEIRS Study participants had non-synonymous, coding region HCP1
      variants. Each of these five had TS above the 84th gender- and ethnic/racial
      group-specific percentile (TS percentiles: 84.7, 91.3, 97.9, 99.5, and 99.9).

PMID- 19176289
TI  - Plasma chitotriosidase activity in multiple sclerosis.
AB  - A recent study has shown that chitotriosidase (Chit) may play a role in the
      pathogenesis of multiple sclerosis (MS). Plasma Chit activity was investigated in
      219 untreated MS patients and 160 healthy controls (HC) by means of a
      fluorometric enzyme activity assay. Chit activity was also measured in a subgroup
      of 46 patients following treatment with interferon-beta (IFNbeta). Overall,
      plasma Chit activity was significantly increased in MS patients compared with HC,
      but no differences were observed between relapsing and progressive clinical
      forms. In addition, Chit activity was similar between patients during relapse and
      patients during clinical remission. Treatment with IFNbeta was associated with a
      significant increase in Chit activity compared with untreated patients in both
      responders and non-responders to treatment. Although these findings suggest a
      role of Chit in MS, our data do not support an association between plasma Chit
      activity and MS clinical course and clinical response to IFNbeta treatment.

PMID- 19176288
TI  - Male osteoporosis: diagnosis and fracture risk evaluation.
AB  - Male osteoporosis is challenging to diagnose and to treat. Underestimation of the
      risk of male osteoporosis, the combined presence of several interwoven causative
      factors in many patients, and uncertainty regarding the absorptiometry cutoffs
      associated with fractures are major obstacles to the diagnosis of male
      osteoporosis and to the identification of men at risk for fractures. The lifetime
      risk of osteoporotic fracture is estimated at 15% among men older than 50 years.
      One-third of proximal femoral fractures occur in men, and the associated
      mortality rate is 2- to 3-fold that in women. In men, nearly half the cases of
      osteoporosis are related to disease, medications, or risk factors. Although the
      criteria for diagnosing male osteoporosis are not agreed on, the definitions
      developed by the World Health Organization can be used provided the reference
      population is composed of young males. An absorptiometry T-score < or = -2.5 is
      useful for diagnosing osteoporosis but fails to adequately predict the fracture
      risk. The identification of men at high risk for fractures requires a combined
      evaluation of bone mineral density data, clinical risk factors, and risk factors
      for falls.

PMID- 19176291
TI  - Primary closure of large inelastic wounds with the use of a tension relief
      bridging device.

PMID- 19176290
TI  - New treatments for ocular hypertension.
AB  - Glaucoma is a neurodegenerative pathology that affects the optic nerve producing
      blindness. This disease is often a consequence of an abnormal increase of
      intraocular pressure (IOP) due to a reduction in the ability of the eye to drain
      a transparent fluid termed aqueous humour. The dynamics of the aqueous humour is
      highly controlled by the autonomic nervous system, mainly the sympathetic,
      regulating its production and parasympathetic controlling the evacuation of
      aqueous humour. This has led pharmaceutical companies to develop chemicals which,
      by acting via different targets can substantially reduce IOP.
      Parasympathomimetics, adrenergic antagonists, plus eventually adrenergic
      agonists, are commonly used for the reduction of IOP and therefore for treatment
      of glaucoma. New substances linked to the nervous system that innervates the eye
      are emerging as interesting candidates. Nucleotides, commonly costored with
      catecholamines or acetylcholine or the indole melatonin, present interesting
      properties reducing IOP. Moreover new technological ideas such as the use of
      siRNA (small interference RNA) to silence protein expression demonstrate the
      relevance of this method to approach ocular hypertension and glaucoma from a
      different point of view. These three main groups of molecules: nucleotides,
      melatonins and siRNAs, are reviewed since they appear as firm candidates for the
      treatment of glaucoma in the near future.

PMID- 19176292
TI  - Scalp-tissue expansion for a chronic burn wound with exposed calvarium.

PMID- 19176296
TI  - Comparison of transfusion requirements for conventional and miniaturized
      extracorporeal circuits.
AB  - OBJECTIVE: Hemodilution is a well-recognized phenomenon of cardiopulmonary bypass
      (CPB). The degree of hemodilution has attendant risks. As the degree of
      hemodilution increases, red blood cell transfusions may be necessary, and the
      risks of blood transfusions are becoming very well recognized. Blood-conservation
      programs are being developed worldwide to establish strategies to reduce
      transfusions. Miniaturized extracorporeal circuits (MECs) are associated with
      less hemodilution than conventional CPB circuits. The use of MECs can be expected
      to be associated with fewer red blood cell transfusions. METHODS: The first 250
      patients who underwent coronary artery bypass grafting, aortic valve replacement,
      or both with the use of a MEC were compared with 200 consecutive patients who had
      similar comorbidities and types of surgery but underwent their operations on a
      conventional bypass circuit. These surgeries were completed between April 2004
      and September 2005 under the care of the same surgical team. The minimum
      acceptable hematocrit on bypass was 22%. Intra- and postoperative transfusion
      rates were measured and compared. RESULTS: For conventional bypass, the
      intraoperative transfusion rate was 36.5%, whereas the rate for the MEC was
      23.3%. The postoperative transfusion rate was 55% for operations performed with
      conventional bypass and 26% for the MEC. The overall in-hospital transfusion rate
      for conventional bypass was 63% and 36% for the MEC. CONCLUSIONS: The data
      indicate that use of MECs leads to a lower transfusion rate than in surgeries in
      which conventional CPB is used.

PMID- 19176297
TI  - Bullet embolism after gunshot injury: a case report.
AB  - We describe a case of gunshot injury presenting with cardiac tamponade in which a
      dummy bullet advanced through the aorta and caused embolization in the right
      renal interlobar artery after passing above the sternoclavicular joint and
      penetrating into the aorta. Emergency surgery with cardiopulmonary bypass was
      performed to repair the cardiac tamponade and aortic injury. Postoperatively, a
      direct abdominal x ray revealed a bullet image, confirmed by an ultrasonography
      examination that demonstrated the presence of a metal object in the right renal
      pelvis. The bullet was considered to have reached the kidney via an arterial
      route and to cause embolization in the distal bed. The procedure was successful,
      and the patient was discharged on postoperative day 8. In gunshot injuries, if
      all entrance points are not paired with exit points, the possibility of an organ
      or extremity embolism caused by the presence of a bullet or shrapnel fragments in
      circulation should be borne in mind, although such occurrences are rare.

PMID- 19176298
TI  - Findings from the National Institute of Nursing Research related to neonatal
      care: 2008 update.

PMID- 19176299
TI  - Abstracts of the 8th National Neonatal Nurses Meeting. Washington, DC, USA.
      October 9-11, 2008.

PMID- 19176301
TI  - The wheel of time.

PMID- 19176302
TI  - Sudden infant death syndrome prevention: a model program for NICUs.
AB  - Health care providers' opinions can influence how parents place their infant to
      sleep. Neonatal nurses can improve how they teach and model safe infant sleep
      practices to parents. To increase neonatal nurses' knowledge, a sudden infant
      death syndrome (SIDS) prevention program was implemented. Program components
      included a computerized teaching tool, a crib card, sleep sacks, and discharge
      instructions. Initial program evaluation showed that 98 percent of infants slept
      supine and 93 percent slept in sleep sacks in open cribs. However, nurses
      continued to swaddle some infants with blankets to improve thermoregulation. To
      increase nursing compliance in modeling safe infant sleep practices, Halo
      SleepSack Swaddles were provided for nurses to use in place of a blanket to
      regulate infant temperature. Recent data show that 100 percent of infants in open
      cribs are now sleeping supine wearing a Halo Swaddle or a traditional Halo
      SleepSack. This model program can easily be replicated to enhance neonatal
      nurses' knowledge about SIDS prevention.

PMID- 19176303
TI  - Prevention of nasal injuries secondary to NCPAP application in the ELBW infant.
AB  - Improved technology and management approaches that have reduced bronchopulmonary
      dysplasia (BPD) have decreased mortality and morbidity in extremely low birth
      weight (ELBW) infants. Early extubation to nasal continuous positive airway
      pressure (NCPAP) decreases the complications associated with long-term oral/nasal
      endotracheal intubation, including BPD, ventilator-associated pneumonia,
      volutrauma, subglottic stenosis, oral palatal grooves, and nasal septum erosion.
      Research and anecdotal evidence have shown that iatrogenic injuries to the nose
      also occur with extended time on NCPAP. Research observing associations between
      the patient interface and nasal injury has shown duration of therapy to be the
      most significant risk factor. Immature skin and developing nasal structures place
      ELBW infants at increased risk for injury. The challenge for NICU caregivers is
      maintaining the ELBW infant on NCPAP for extended periods without nasal injury.
      Appropriate protocols, practice guidelines, and staff education can decrease
      these injuries.

PMID- 19176304
TI  - A preterm infant with intestinal lymphangiectasia: a diagnostic dilemma.
AB  - Intestinal lymphangiectasia (IL) is a potentially fatal disorder of the lymphatic
      system if it is not recognized and proper treatment initiated. The disease is
      characterized by lymphocytopenia, peripheral edema, and hypoalbuminemia. Because
      IL is a rare disease, the symptoms, diagnostic workup, and treatment are
      unfamiliar to many clinicians. Current literature documents only a few reported
      cases of IL in a preterm infant. This case report of a preterm infant reviews
      history, symptomatology, and the diagnostic workup performed. The steps in making
      the diagnosis, the treatment, and the prognosis of this condition are also
      presented.

PMID- 19176305
TI  - News of the Academy of Neonatal Nursing.

PMID- 19176306
TI  - Ganciclovir: antiviral therapy for congenital cytomegalovirus.

PMID- 19176308
TI  - Fad, frenzy, or future? A review of the Institute of Medicine's report on the
      direction of evidence-based practice.

PMID- 19176309
TI  - When ventilator-associated pneumonias haunt your NICU--one unit's story.

PMID- 19176312
TI  - Multiple mechanisms of germ cell loss in the perinatal mouse ovary.
AB  - In the perinatal ovary of most mammals, external and internal factors establish a
      primordial follicle reserve that specifies the duration of the reproductive
      lifespan of a given species. We analyzed the mechanism of follicle loss and
      survival in C57BI/6 mice using static and dynamic assays of apoptosis, autophagy,
      and ovarian morphogenesis. We confirm an initial loss soon after birth, when
      about 44% of the germ cells detectable at the end of the fetal period abruptly
      disappear. The observations that (1) few germ or somatic cells were apoptotic in
      newborn ovaries, (2) vitally stained organ cultures exhibit active extrusion of
      non-apoptotic germ cells and (3) germ-cell lysosome amplification occurs at birth
      suggested that additional mechanisms are involved in perinatal germ cell loss.
      Newborn mouse ovaries cultured in the pH sensitive dye lysotracker red exhibit an
      increased incidence of acidified non-apoptotic germ cells when maintained in the
      absence but not in the presence of serum, implying a role for autophagy in germ
      cell attrition. Inhibitors of autophagy, but not apoptosis, reduce germ cell
      acidification induced by serum starvation in ovary organ cultures and protein
      mediators of both autophagy and apoptosis are expressed at birth. From these
      findings we suggest that multiple perinatal mechanisms establish the primordial
      follicle reserve in mice.

PMID- 19176310
TI  - REV1 is implicated in the development of carcinogen-induced lung cancer.
AB  - The somatic mutation hypothesis of cancer predicts that reducing the frequency of
      mutations induced by carcinogens will reduce the incidence of cancer. To examine
      this, we developed an antimutator strategy based on the manipulation of the level
      of a protein required for mutagenic bypass of DNA damage induced by the
      ubiquitous carcinogen benzo[a]pyrene. The expression of this protein, REV1, was
      reduced in mouse cells using a vector encoding a gene-specific targeting
      ribozyme. In the latter cells, mutagenesis induced by the activated form of
      benzo[a]pyrene was reduced by >90%. To examine if REV1 transcripts could be
      lowered in vivo, the plasmid was complexed with polyethyleneimine, a nonviral
      cationic polymer, and delivered to the lung via aerosol. The endogenous REV1
      transcript in the bronchial epithelium as determined by quantitative real-time
      PCR in laser capture microdissected cells was reduced by 60%. There was a
      significant decrease in the multiplicity of carcinogen-induced lung tumors from
      6.4 to 3.7 tumors per mouse. Additionally, REV1 inhibition completely abolished
      tumor formation in 27% of the carcinogen-exposed mice. These data support the
      central role of the translesion synthesis pathway in the development of lung
      cancer. Further, the selective modulation of members of this pathway presents
      novel potential targets for cancer prevention. The somatic mutation hypothesis of
      cancer predicts that the frequency of cancers will also be reduced.

PMID- 19176311
TI  - Expression of ovarian tumour suppressor OPCML in the female CD-1 mouse
      reproductive tract.
AB  - Opioid binding protein/cell adhesion molecule-like gene (OPCML) is frequently
      inactivated in epithelial ovarian cancer, but the role of this membrane protein
      in normal reproductive function is unclear. The ovarian surface epithelium (OSE)
      is thought to be the cell of origin of most epithelial ovarian cancers, some of
      which arise after transformation of OSE cells lining ovarian inclusion cysts,
      formed during ovulation. We used immunohistochemistry, immunoblotting and
      quantitative RT-PCR (qRT-PCR) to investigate OPCML expression in the uteri and
      ovaries of cycling 3-month CD-1 mice, as well as in ovaries from older mice
      containing inclusion cysts derived from rete ovarii tubules. Immunoblotting
      showed OPCML bands in uterine, but not whole ovarian or muscle extracts. Strong
      OPCML immunoreactivity was observed in oviduct, rete ovarii and uterus, whereas
      in ovary more immunoreactivity was seen in granulosa cells than OSE. No staining
      was observed in OSE around ovulation sites, where OSE cells divide to cover the
      site. OPCML immunoreactivity was also weaker in more dysplastic cells lining
      large ovarian inclusion cysts, compared with normal rete ovarii. No significant
      changes in Opcml mRNA expression were observed in whole ovarian and uterine
      extracts at different stages of the cycle. We conclude that murine OPCML is more
      consistently expressed in cells lining the uterus, oviduct and rete ovarii than
      in ovary and is not expressed in OSE associated with ovulation sites. This
      observation supports the hypothesis that a proportion of epithelial ovarian
      cancers arise from ductal cells and other epithelia of the secondary Mullerian
      system, rather than the OSE.

PMID- 19176314
TI  - Advancing the study of violence against women: evolving research agendas into
      science.
AB  - Decades of research produced by multiple disciplines has documented withering
      rates of violence against women in the United States and around the globe. To
      further an understanding of gendered violence, a field of research has developed,
      but recent critiques have highlighted weaknesses that inhibit a full scientific
      exploration of these crimes and their impacts. This review extends beyond prior
      reviews to explore the field's unique challenges, its community of scientists,
      and the state of its written knowledge. The review argues for moving beyond
      "research agendas" and proposes creation of a transdisciplinary science for the
      field of study of violence against women.

PMID- 19176313
TI  - Relationship of vascular perfusion of the wall of the preovulatory follicle to in
      vitro fertilisation and embryo development in heifers.
AB  - The effect of the extent of vascular perfusion of the wall of the preovulatory
      follicle on in vitro cleavage rate of the recovered oocyte and embryo development
      to >8 cells was studied in 52 heifers. Heifers received a luteolytic dose of
      prostaglandin F2alpha (PGF2alpha) when the largest follicle was > or =11 mm. An
      ovulation-inducing injection of GnRH was given 36 h later (hour 0), and
      collection of follicular fluid and the oocyte was done at hour 26. Vascular
      perfusion of the follicular wall was assessed by colour Doppler ultrasonography
      at hours 0 and 26. Each of the recovered oocytes (41/52; 79%) was mature
      (extruded polar body). Cleavage and embryo development were assessed at 48 h and
      120 h respectively, after in vitro fertilisation (IVF). The percentage of cleaved
      oocytes and >8 cell embryos was 80% (31/39) and 55% (17/31) respectively.
      Vascular perfusion of the follicular wall was greater (lower pulsatility index;
      P<0.001) for follicles that produced cleaved versus non-cleaved oocytes and
      greater (P<0.04) for follicles that produced >8 cell versus < or =8 cell embryos.
      Percentage of follicular wall with Doppler signals of blood flow was greater
      (P<0.001) for >8 cell versus < or =8 cell embryos. Follicular-fluid concentration
      of free IGF1 was lower for cleaved oocytes (P<0.001) and >8 cell embryos
      (P<0.05), and oestradiol was lower (P<0.05) for >8 cell embryos. Results
      supported the hypothesis that greater vascular perfusion of the wall of the
      preovulatory follicle was positively associated with IVF and embryo development.

PMID- 19176315
TI  - Cofactors for low serum albumin levels among HIV-infected individuals in Southern
      India.
AB  - BACKGROUND AND AIMS: Malnutrition and low serum albumin among human
      immunodeficiency virus (HIV)-infected individuals are cofactors for HIV disease
      progression. The present study aimed to identify the proportion of HIV-infected
      individuals with low serum albumin and the possible cofactors among highly active
      antiretroviral therapy (HAART) experienced and HAART naive individuals. METHODS:
      A total of 835 HIV-infected individuals (HAART-experienced, HAART-naive) were
      included in the study. RESULTS: Of the 835 individuals, 44.6% had normal (4.2-5.2
      g/dL) and 55.4% had abnormal (<4.2 g/dL) albumin levels. The abnormal group had
      significantly lower body mass index (BMI) compared with the normal group (P =
      .02). Among those with abnormal albumin, 388 (84%) were HAART experienced
      compared with 239 (64%) with normal albumin (P < .001). Among the abnormal group,
      259 (55.9%) had CD4 count <200 cells/mL as compared with 124 (33.3%) in the
      normal group (P < .001). CONCLUSIONS: CD4 count and lower were the major
      cofactors for low serum albumin among HIV-infected individuals. Therefore, serum
      albumin would be a useful biochemical test for HIV disease in resource-limited
      settings.

PMID- 19176316
TI  - Dendritic cell homeostasis.
AB  - Dendritic cells (DCs) are a heterogeneous fraction of rare hematopoietic cells
      that coevolved with the formation of the adaptive immune system. DCs efficiently
      process and present antigen, move from sites of antigen uptake to sites of
      cellular interactions, and are critical in the initiation of immune responses as
      well as in the maintenance of self-tolerance. DCs are distributed throughout the
      body and are enriched in lymphoid organs and environmental contact sites. Steady
      state DC half-lives account for days to up to a few weeks, and they need to be
      replaced via proliferating hematopoietic progenitors, monocytes, or tissue
      resident cells. In this review, we integrate recent knowledge on DC progenitors,
      cytokines, and transcription factor usage to an emerging concept of in vivo DC
      homeostasis in steady-state and inflammatory conditions. We furthermore highlight
      how knowledge of these maintenance mechanisms might impact on understanding of DC
      malignancies as well as posttransplant immune reactions and their respective
      therapies.

PMID- 19176317
TI  - Human plasmacytoid dendritic cells are unresponsive to bacterial stimulation and
      require a novel type of cooperation with myeloid dendritic cells for maturation.
AB  - Dendritic cell (DC) populations play unique and essential roles in the detection
      of pathogens, but information on how different DC types work together is limited.
      In this study, 2 major DC populations of human blood, myeloid (mDCs) and
      plasmacytoid (pDCs), were cultured alone or together in the presence of pathogens
      or their products. We show that pDCs do not respond to whole bacteria when
      cultured alone, but mature in the presence of mDCs. Using purified stimuli, we
      dissect this cross-talk and demonstrate that mDCs and pDCs activate each other in
      response to specific induction of only one of the cell types. When stimuli for
      one or both populations are limited, they synergize to reach optimal activation.
      The cross-talk is limited to enhanced antigen presentation by the nonresponsive
      population with no detectable changes in the quantity and range of cytokines
      produced. We propose that each population can be a follower or leader in immune
      responses against pathogen infections, depending on their ability to respond to
      infectious agents. In addition, our results indicate that pDCs play a secondary
      role to induce immunity against human bacterial infections, which has
      implications for more efficient targeting of DC populations with improved
      vaccines and therapeutics.

PMID- 19176318
TI  - FAS-L, IL-10, and double-negative CD4- CD8- TCR alpha/beta+ T cells are reliable
      markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS
      loss of function.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is characterized by splenomegaly,
      lymphadenopathy, hypergammaglobulinemia, accumulation of double-negative
      TCRalphabeta(+) CD4(-)CD8(-) T cells (DNT cells), and autoimmunity. Previously,
      DNT cell detection and a functional defect of T cells in a FAS-induced apoptosis
      test in vitro had been used for ALPS diagnosis. However, a functional defect can
      also be detected in mutation-positive relatives (MPRs) who remain free of any
      ALPS-related disease. In contrast, lymphocytes from patients carrying a somatic
      mutation of FAS exhibit normal sensitivity to FAS-induced apoptosis in vitro. We
      assessed the soluble FAS-L concentration in the plasma of ALPS patients carrying
      FAS mutations. Overall, we showed that determination of the FAS-L represents,
      together with the IL-10 concentration and the DNT cell percentage, a reliable
      tool for the diagnosis of ALPS.

PMID- 19176319
TI  - Antigen-loaded exosomes alone induce Th1-type memory through a B-cell-dependent
      mechanism.
AB  - Exosomes are nanovesicles harboring proteins important for antigen presentation.
      We compared the potency of differently loaded exosomes, directly loaded with
      OVA(323-339) peptide (Pep-Exo) or exosomes from OVA-pulsed DCs (OVA-Exo), for
      their ability to induce specific T-cell proliferation in vitro and in vivo. Both
      Pep-Exo and OVA-Exo elicited specific transgenic T-cell proliferation in vitro,
      with the Pep-Exo being more efficient. In contrast, only OVA-Exo induced specific
      T-cell responses in vivo highlighting the importance of indirect loading
      strategies in clinical applications. Coadministration of whole OVA overcame the
      unresponsiveness with Pep-Exo but still elicited a lower response compared with
      OVA-Exo. In parallel, we found that OVA-Exo not only augmented the specific T
      cell response but also gave a Th1-type shift and an antibody response even in the
      absence of whole OVA. We detected IgG2a and interferon-gamma production from
      splenocytes showing the capability of exosomes to provide antigen for B-cell
      activation. Furthermore, we found that B cells are needed for exosomal T-cell
      stimulation because Bruton tyrosine kinase-deficient mice showed abrogated B- and
      T-cell responses after OVA-Exo immunization. These findings reveal that exosomes
      are potent immune regulators and are relevant for the design of vaccine adjuvants
      and therapeutic intervention strategies to modulate immune responses.

PMID- 19176320
TI  - The skinny on adiponectin.

PMID- 19176321
TI  - Peripheral administration of nesfatin-1 reduces food intake in mice: the leptin
      independent mechanism.
AB  - Nesfatin-1 is a novel satiety molecule in the hypothalamus and is also present in
      peripheral tissues. Here we sought to identify the active segment of nesfatin-1
      and to determine the mechanisms of its action after peripheral administration in
      mice. Intraperitoneal injection of nesfatin-1 suppressed food intake in a dose
      dependent manner. Nesfatin-1 has three distinct segments; we tested the effect of
      each segment on food intake. Injection of the midsegment decreased food intake
      under leptin-resistant conditions such as db/db mice and mice fed a high-fat
      diet. After injection of the midsegment, expression of c-Fos was significantly
      activated in the brainstem nucleus tractus solitarius (NTS) but not in the
      hypothalamic arcuate nucleus; the nicotinic cholinergic pathway to the NTS
      contributed to midsegment-induced anorexia. Midsegment injection significantly
      increased expression of proopiomelanocortin and cocaine- and amphetamine
      regulated transcript genes in the NTS but not in the arcuate nucleus.
      Investigation of mutant midsegments demonstrated that a region with amino acid
      sequence similarity to the active site of agouti-related peptide was
      indispensable for anorexigenic induction. Our findings indicate that the
      midsegment of nesfatin-1 causes anorexia, possibly by activating POMC and CART
      neurons in the NTS via a leptin-independent mechanism after peripheral
      stimulation.

PMID- 19176322
TI  - Androgen-induced progression of arterial calcification in apolipoprotein E-null
      mice is uncoupled from plaque growth and lipid levels.
AB  - Arterial calcification has prognostic significance for cardiovascular outcomes,
      but its pathogenesis remains unclear. Calcification increases with age, but its
      prevalence in men suggests hormonal influence. In this study we analyzed the
      effect of exogenous androgens on calcification of advanced atherosclerotic
      lesions in the arterial tree of gonadally intact 34-wk-old male and female
      apolipoprotein E-null mice. Testosterone (T) increased calcification 3- to 4-fold
      (P < 0.05) in lesions of the innominate artery and aortic sinus. A
      nonaromatizable androgen, dihydrotestosterone, also increased lesion
      calcification in the innominate artery (2.4-fold, P < 0.05) but not the aortic
      sinus. The androgen-induced effects were independent of sex and occurred despite
      corresponding reductions in plaque area, the latter correlating inversely with
      increased serum high-density lipoprotein cholesterol levels. Androgen-induced
      calcification in the innominate artery was observed with up-regulation of local
      androgen receptor (AR) expression in response to T and dihydrotestosterone for
      both males and females but neither androgen influenced innominate artery estrogen
      receptor (ER)-alpha or -beta expression in either sex. Conversely, T-induced
      calcification in the aortic sinus was associated with down-regulation of ERalpha
      but not ERbeta expression in both sexes, whereas androgen-induced AR expression
      was increased in female but decreased in male mice. This study demonstrates for
      the first time that calcification of advanced atherosclerotic lesions is an
      androgen-sensitive process and postulates potential roles for both AR- and ER
      mediated pathways in androgen-induced vascular calcification. We demonstrate a
      novel direct link between vascular calcification and the major male hormone, T,
      uncoupled from conventional relationships with plaque growth and lipid levels.

PMID- 19176323
TI  - Rapid estrogen receptor-alpha activation improves ischemic tolerance in aged
      female rats through a novel protein kinase C epsilon-dependent mechanism.
AB  - The effects of estrogen deficiency on the loss of cardioprotection with advancing
      age are complex and poorly understood. A major focus of the current study was to
      uncover a cardioprotective role for rapid, nongenomic estrogen receptor (ER)
      signaling in the aged female myocardium. We hypothesized that selective ERalpha
      activation in aged females would reduce infarct size in part, through reversal of
      age-associated reductions in mitochondrial protein kinase Cepsilon (PKCepsilon).
      Hearts isolated from adult (6 month old) and aged (23-24 months old) female F344
      rats with ovaries removed (n = 20 per group) were subjected to
      ischemia/reperfusion (47 min global ischemia). Rats were injected sc with the
      ERalpha agonist propylpyrazole triol (PPT) or vehicle 45 min before heart
      isolation (5 microg/kg). Infarct size was greatest in aged vs. adult
      ovariectomized rats, significantly reduced by PPT, and the protection reversed by
      prior administration of the ER inhibitor ICI 182,780 (3 mg/kg). Increased ERalpha
      particulate targeting occurred after PPT in conjunction with reversal of age
      related reductions in nuclear PKCepsilon, mitochondrial PKCepsilon and pAkt (P <
      0.05). PPT also increased mRNA levels for the PKCepsilon anchoring protein,
      receptor for activated C kinase2 (RACK2; P < 0.05). Our data suggest, for the
      first time, that selective ERalpha activation reduces ischemic injury in the
      aged, estrogen-deficient heart through a mechanism involving nongenomic
      redistribution of ERalpha and PKCepsilon activation. A novel feed-forward
      transcriptional mechanism to potentially enhance PKCepsilon-RACK2 interactions
      was also observed. Collectively, our findings may provide key insight into
      developing targeted therapeutic interventions in postmenopausal women to reduce
      ischemia/reperfusion injury, including selective ERalpha mimetics.

PMID- 19176332
TI  - State of the science of molecular imaging: 2008.

PMID- 19176328
TI  - Fatigue in a representative population of older persons and its association with
      functional impairment, functional limitation, and disability.
AB  - BACKGROUND: Older persons often complain of fatigue, but the functional
      consequences of this symptom are unclear. The aim of the present study was to
      evaluate fatigue and its association with measures of physical function and
      disability in a representative sample of the older population. METHODS: Cross
      sectional data from a population-based sample of 1,055 Italian men and women aged
      65 and older were analyzed. Fatigue was defined according to two questions
      evaluating whether participants felt that "everything was an effort" and/or they
      "could not get going" on three or more days in the past week. Objective measures
      of physical function were handgrip strength, the Short Physical Performance
      Battery (SPPB), and 400-m walking speed. Disability was defined as the inability
      to complete the 400-m walk test and self-reported difficulty in activities of
      daily living (ADL) and instrumental activities of daily living (IADL). RESULTS:
      The prevalence of fatigue was higher in women (29%) than in men (15%). In age
      adjusted analyses, fatigued men and women had weaker handgrip strength, lower
      SPPB score, slower walking speed, and higher mobility, ADL, and IADL disability
      than nonfatigued persons. Further adjustment for health behaviors, diseases,
      inflammatory markers, and thyroid function generally reduced the relationship
      between fatigue and functional outcomes, but fatigue remained significantly
      associated with SPPB score, walking speed, and mobility and IADL disability.
      CONCLUSIONS: Older persons who report fatigue had significantly poorer functional
      status than those who did not report this symptom. The causal link between
      fatigue and these outcomes should be further investigated.

PMID- 19176333
TI  - Physics applications in nuclear medicine: 2008 in review.

PMID- 19176337
TI  - From the Medical Internal Radiation Dose Committee.

PMID- 19176346
TI  - Helicobacter pylori can multiply in autophagic vesicles.

PMID- 19176347
TI  - Genetic ablation of Nrf2 enhances susceptibility to acute lung injury after
      traumatic brain injury in mice.
AB  - Previous studies have shown that nuclear factor erythroid 2-related factor 2
      (Nrf2) plays a unique role in many physiological stress processes. The present
      study investigated the role of Nrf2 in the regulation of traumatic brain injury
      (TBI)-induced acute lung injury (ALI). Wild-type Nrf2 (+/+) and Nrf2 (-/-)
      deficient mice were subjected to a moderately severe weight-drop impact head
      injury. Pulmonary capillary permeability (PCP), wet/dry weight ratio, apoptosis,
      inflammatory cytokines and antioxidant/detoxifying enzymes were measured at 24 h
      after TBI. Mice lacking Nrf2 were found to be more susceptible to TBI-induced
      ALI, as characterized by the higher increase in PCP, wet/dry weight ratio and
      alveolar cells apoptosis after TBI. This exacerbation of lung injury in Nrf2
      deficient mice was associated with increased pulmonary mRNA and protein
      expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF
      alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6); and with decreased
      pulmonary mRNA expression and enzymatic activities of antioxidant and detoxifying
      enzymes including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S
      transferase alpha1 (GST-alpha1)--as compared with their wild-type Nrf2 (+/+)
      counterparts after TBI. The results of the present study suggest that Nrf2
      reduces TBI-induced acute lung injury, possibly by decreasing pulmonary
      inflammation and inducing antioxidant and detoxifying enzymes.

PMID- 19176348
TI  - Retention of nanoparticles-labeled bone marrow mononuclear cells in the isolated
      ex vivo perfused heart after myocardial infarction in animal model.
AB  - Cell therapy of myocardial infarction (MI) is under clinical investigation, yet
      little is known about its underlying mechanism of function. Our aims were to
      induce a sub-lethal myocardial infarction in a rabbit, to evaluate the abilities
      of labeled bone marrow mononuclear cells to migrate from the vessel bed into
      extracellular space of the myocardium, and to evaluate the short-term
      distribution of cells in the damaged left ventricle. Sub-lethal myocardial
      infarction was induced in rabbits by ligation of the left coronary vessel branch
      (in vivo). The Langendorff heart perfusion model (ex vivo) was used in the next
      phase. The hearts subjected to MI induction were divided into 3 groups (P1-P3),
      and hearts without MI formed a control group (C). Nanoparticles-labeled bone
      marrow mononuclear cells were injected into coronary arteries via the aorta.
      Perfusion after application lasted 2 minutes in the P1 group, 10 minutes in the
      P2 and C groups, and 25 minutes in the P3 group. The myocardium of the left
      ventricle was examined histologically, and the numbers of labeled cells in
      vessels, myocardium, and combined were determined. The numbers of detected cells
      in the P1 and C groups were significantly lower than in the P2 and P3 groups. In
      the P2 and P3 groups, the numbers of cells found distally from the ligation were
      significantly higher than proximally from the ligation site. Bone marrow
      mononuclear cells labeled with iron oxide nanoparticles proved the ability to
      migrate in the myocardium interstitium with significantly higher affinity for the
      tissue damaged by infarction.

PMID- 19176349
TI  - GLUT8, the enigmatic intracellular hexose transporter.
AB  - GLUT8 is a class III sugar transporter predominantly expressed in testis and
      brain. In contrast to the class I and class II transporters, hydrophobicity plots
      predict a short extracellular loop between transmembrane domain (TM)1 and TM2 and
      a long extracellular loop between TM9 and TM10 that contains the only N
      glycosylation site. In vitro translated GLUT8 migrates as a 35-kDa protein that
      is glycosylated in the presence of microsomal membranes. In heterologous
      expression systems, glucose transport activity (Km of 2 mM) was inhibited by
      fructose and galactose. The transporter carries an NH2-terminal
      endosomal/lysosomal targeting motif ([DE]XXXL[LI]). Accordingly, constitutive
      GLUT8 has been found to be associated with endosomes and lysosomes but also with
      membranes of the endoplasmic reticulum. A similar distribution was detected after
      overexpression of wild-type or tagged GLUT8 in different cell systems. In these
      cells, none of the conventional signals tested induced a translocation of GLUT8
      to the plasma membrane. Therefore, GLUT8 appears to catalyze transport of sugars
      or sugar derivatives through intracellular membranes. Slc2a8 knockout mice were
      viable, developed normally, and showed mild alterations in brain (increased
      proliferation of neuronal cells in dentate gyrus of the hippocampus,
      hyperactivity), heart (impaired transmission of electrical wave through the
      atrium), and sperm cells (reduced number of motile sperm cells associated with
      reduced mitochondrial membrane potential and ATP levels in sperm). The links
      between molecular function, cellular localization and phenotype of the knockout
      mouse is unclear and remains to be determined.

PMID- 19176350
TI  - Maternal obesity downregulates myogenesis and beta-catenin signaling in fetal
      skeletal muscle.
AB  - Skeletal muscle is one of the primary tissues responsible for insulin resistance
      and type 2 diabetes (T2D). The fetal stage is crucial for skeletal muscle
      development. Obesity induces inflammatory responses, which might regulate
      myogenesis through Wnt/beta-catenin signaling. This study evaluated the effects
      of maternal obesity (>30% increase in body mass index) during pregnancy on
      myogenesis and the Wnt/beta-catenin and IKK/NF-kappaB pathways in fetal skeletal
      muscle using an obese pregnant sheep model. Nonpregnant ewes were assigned to a
      control group (C; fed 100% of National Research Council recommendations; n=5) or
      obesogenic (OB; fed 150% of National Research Council recommendations; n=5) diet
      from 60 days before to 75 days after conception (term approximately 148 days)
      when fetal semitendenosus skeletal muscle was sampled for analyses. Myogenic
      markers including MyoD, myogenin, and desmin contents were reduced in OB compared
      with C fetal semitendenosus, indicating the downregulation of myogenesis. The
      diameter of primary muscle fibers was smaller in OB fetal muscle. Phosphorylation
      of GSK3beta was reduced in OB compared with C fetal semitendenosus. Although the
      beta-catenin level was lower in OB than C fetal muscle, more beta-catenin was
      associated with FOXO3a in the OB fetuses. Moreover, we found phosphorylation
      levels of IKKbeta and RelA/p65 were both increased in OB fetal muscle. In
      conclusion, our data showed that myogenesis and the Wnt/beta-catenin signaling
      pathway were downregulated, which might be due to the upregulation of
      inflammatory IKK/NF-kappaB signaling pathways in fetal muscle of obese mothers.

PMID- 19176351
TI  - Endurance swimming stimulates transepithelial calcium transport and alters the
      expression of genes related to calcium absorption in the intestine of rats.
AB  - Endurance impact exercise, e.g., running, is known to enhance the intestinal
      calcium absorption. However, nonimpact exercise, e.g., swimming, is more
      appropriate for osteoporotic patients with cardiovascular diseases or disorders
      of bone and joint, but the effect of swimming on the intestinal calcium transport
      was unknown. This study, therefore, aimed to investigate the transepithelial
      calcium transport and the expression of related genes in the intestine of rats
      trained to swim nonstop 1 h/day, 5 days/wk for 2 wk. We found that endurance
      swimming stimulated calcium transport in the duodenum, proximal jejunum, and
      cecum, while decreasing that in the proximal colon. Swimming affected neither the
      transepithelial potential difference nor resistance. As demonstrated by real-time
      PCR, the small intestine, especially the duodenum, responded to swimming by
      upregulating a number of genes related to the transcellular calcium transport,
      i.e., TRPV5, TRPV6, calbindin-D9k, PMCA1b, and NCX1, and the paracellular calcium
      transport, i.e., ZO-1, ZO-2, ZO-3, cingulin, occludin, and claudins, as well as
      nuclear receptor of 1,25(OH)2D3. In contrast, swimming downregulated those genes
      in the colon. Microarray analysis showed that swimming also altered the
      expression of duodenal genes related to the transport of several ions and
      nutrients, e.g., Na+, K+, Cl-, glucose, and amino acids. In conclusion, endurance
      swimming enhanced intestinal calcium absorption, in part, by upregulating the
      calcium transporter genes. The present microarray study also provided relevant
      information for further investigations into the intestinal nutrient and
      electrolyte transport during nonimpact exercise.

PMID- 19176352
TI  - Involvement of the vitamin D receptor in energy metabolism: regulation of
      uncoupling proteins.
AB  - Recent studies have established that vitamin D plays multiple biological roles
      beyond calcium metabolism; however, whether vitamin D is involved in energy
      metabolism is unknown. To address this question, we characterized the metabolic
      phenotypes of vitamin D receptor (VDR)-null mutant mice. Under a normocalcemic
      condition, VDR-null mice displayed less body fat mass and lower plasma
      triglyceride and cholesterol levels compared with wild-type (WT) mice; when
      placed on a high-fat diet, VDR-null mice showed a slower growth rate and
      accumulated less fat mass globally than WT mice, even though their food intake
      and intestinal lipid transport capacity were the same as WT mice. Consistent with
      the lower adipose mass, plasma leptin levels were lower and white adipocytes were
      histologically smaller in VDR-null mice than WT mice. The rate of fatty acid beta
      oxidation in the white adipose tissue was higher, and the expression of
      uncoupling protein (UCP) 1, UCP2 and UCP3 was markedly upregulated in VDR-null
      mice, suggesting a higher energy expenditure in the mutant mice. Experiments
      using primary brown fat culture confirmed that 1,25-dihydroxyvitamin D3 directly
      suppressed the expression of the UCPs. Consistently, the energy expenditure,
      oxygen consumption, and CO2 production in VDR-null mice were markedly higher than
      in WT mice. These data indicate that vitamin D is involved in energy metabolism
      and adipocyte biology in vivo in part through regulation of beta-oxidation and
      UCP expression.

PMID- 19176353
TI  - Human apolipoprotein D overexpression in transgenic mice induces insulin
      resistance and alters lipid metabolism.
AB  - Apolipoprotein D (apoD), a widely expressed lipocalin, has the capacity to
      transport small hydrophobic molecules. Although it has been proposed that apoD
      may have multiple tissue-specific, physiological ligands and functions, these
      have yet to be identified. To gain insight in some of its functions, we generated
      transgenic mice overexpressing human apoD (H-apoD) under the control of neuron
      specific promoters. In Thy-1/apoD and NSE/apoD mice, expression of H-apoD was
      strong in the nervous system although weakly detected in peripheral organs such
      as the liver and blood cells. These mice displayed not entirely anticipated
      metabolic defects. Although they are not obese and have normal lipid
      concentration in circulation, Thy-1/apoD and NSE/apoD mice are glucose
      intolerant, insulin resistant, and develop hepatic steatosis. The steatosis and
      its associated insulin resistance are correlated with impairments in hepatic
      lipogenesis. However, they are not strongly related with inflammation. This
      impaired insulin response is not caused by a decrease in circulating leptin or a
      modulation of adiponectin and resistin levels. These results suggest that
      variations in the levels and/or sites of apoD expression influence the lipid and
      glucose metabolism, consolidating apoD as a target for insulin-resistance-related
      disorders.

PMID- 19176354
TI  - Berberine improves lipid dysregulation in obesity by controlling central and
      peripheral AMPK activity.
AB  - AMP-activated protein kinase (AMPK) plays an important role in regulating whole
      body energy homeostasis. Recently, it has been demonstrated that berberine (BBR)
      exerts antiobesity and antidiabetic effects in obese and diabetic rodent models
      through the activation of AMPK in peripheral tissues. Here we show that BBR
      improves lipid dysregulation and fatty liver in obese mice through central and
      peripheral actions. In obese db/db and ob/ob mice, BBR treatment reduced liver
      weight, hepatic and plasma triglyceride, and cholesterol contents. In the liver
      and muscle of db/db mice, BBR promoted AMPK activity and fatty acid oxidation and
      changed expression of genes involved in lipid metabolism. Additionally,
      intracerebroventricular administration of BBR decreased the level of malonyl-CoA
      and stimulated the expression of fatty acid oxidation genes in skeletal muscle.
      Together, these data suggest that BBR would improve fatty liver in obese
      subjects, which is probably mediated not only by peripheral AMPK activation but
      also by neural signaling from the central nervous system.

PMID- 19176355
TI  - Estrogen receptor-alpha and -beta and aromatase knockout effects on lower limb
      muscle mass and contractile function in female mice.
AB  - Estrogen (E2) is reported to regulate skeletal muscle mass and contractile
      function; whether E2 exerts its effects through estrogen receptor-alpha (ERalpha)
      or -beta (ERbeta) is unclear. We determined the effect of ERalpha or ERbeta
      elimination on muscle mass and contractile function in multiple muscles of the
      lower limb, muscles with different locomotor tasks and proportions of fiber types
      I and II: soleus (Sol), plantaris (Plan), tibialis anterior (TA), and
      gastrocnemius (Gast) in mature female mice. To determine E2 elimination effects
      on muscle, we also used aromatase (Ar) knockout (KO) and wild-type (WT) mice.
      ERalpha and ArKO body weights were approximately 10 and 20% higher than WT.
      Although muscle mass tended to show a commensurate increase in both groups, only
      the TA was significantly larger in ERalpha (P<0.05). Ratios of muscle mass to
      body mass revealed significantly lower values for Gast and TA in ArKO mice
      (P<0.05). Tetanic tension (Po) per calculated anatomical cross-sectional area
      (aCSA) in ERalpha KO was lower in TA and Gast than in WT. Lower Po/aCSA in
      ERalpha KO Gast and TA was also supported histologically by significantly less
      Po/fiber areas (P<0.05). ArKO mice also had lower Po/aCSA in Gast and TA compared
      with WT. ERbeta KO and WT mice were comparable in all measures. Our results
      support the hypothesis that E2 effects on skeletal muscle are mediated in part
      via the ERalpha but that E2 effects may be mediated via more than one mechanism
      or receptor.

PMID- 19176356
TI  - PET study of 11C-acetoacetate kinetics in rat brain during dietary treatments
      affecting ketosis.
AB  - Normally, the brain's fuel is glucose, but during fasting it increasingly relies
      on ketones (beta-hydroxybutyrate, acetoacetate, and acetone) produced in liver
      mitochondria from fatty acid beta-oxidation. Although moderately raised blood
      ketones produced on a very high fat ketogenic diet have important clinical
      effects on the brain, including reducing seizures, ketone metabolism by the brain
      is still poorly understood. The aim of the present work was to assess brain
      uptake of carbon-11-labeled acetoacetate (11C-acetoacetate) by positron emission
      tomography (PET) imaging in the intact, living rat. To vary plasma ketones, we
      used three dietary conditions: high carbohydrate control diet (low plasma
      ketones), fat-rich ketogenic diet (raised plasma ketones), and 48-h fasting
      (raised plasma ketones). 11C-acetoacetate metabolism was measured in the brain,
      heart, and tissue in the mouth area. Using 11C-acetoacetate and small animal PET
      imaging, we have noninvasively quantified an approximately seven- to eightfold
      enhanced brain uptake of ketones on a ketogenic diet or during fasting. This
      opens up an opportunity to study brain ketone metabolism in humans.

PMID- 19176357
TI  - Role of the liver in glucose homeostasis in PI 3-kinase p85alpha-deficient mice.
AB  - Phosphoinositide 3-kinase (PI3K) p85alpha-deficient mice exhibit hypoglycemia as
      a result of increased insulin sensitivity and glucose uptake in peripheral
      tissues. Although PI3K is central to the metabolic actions of insulin, its
      mechanism of action in liver is not well understood. In the present study, we
      investigated hepatic insulin signaling and glucose homeostasis in p85alpha
      deficient and wild-type mice. In the livers of p85alpha-deficient mice, p50alpha
      played a compensatory role in insulin-stimulated PI3K activation by binding to
      insulin receptor substrate (IRS)-1/2. In p85alpha-deficient mice, the ratio of
      p50alpha over p110 catalytic subunit of PI3K in the liver was higher than in the
      muscles. PI3K activity associated with IRS-1/2 was not affected by the lack of
      p85alpha in the liver. Insulin-stimulated Akt and phosphatase and tensin
      homologue deleted on chromosome 10 (PTEN) activities in the liver were similar in
      p85alpha-deficient and wild-type mice. A hyperinsulinemic-euglycemic clamp study
      revealed that the glucose infusion rate and the rate of disappearance were higher
      in p85alpha-deficient mice than in wild-type mice but that endogenous glucose
      production tended to be higher in p85alpha-deficient mice than in wild-type mice.
      Consistent with this finding, the expression of glucose-6-phosphatase and
      phosphoenolpyruvate carboxykinase in livers after fasting was higher in p85alpha
      deficient mice than in wild-type mice. After mice were fasted, the intrahepatic
      glucose-6-phosphate level was almost completely depleted in p85alpha-deficient
      mice. The glycogen content fell to nearly zero as a result of glycogenolysis
      shortly after the initiation of fasting in p85alpha-deficient mice. The absence
      of an increase in insulin-stimulated PI3K activation in the liver of p85alpha
      deficient mice, unlike the muscles, may be associated with the molecular balance
      between the regulatory subunit and the catalytic subunit of PI3K. Gluconeogenesis
      was rather elevated in p85alpha-deficient mice, compared with in wild-type mice,
      and the liver seemed to partially compensate for the increase in glucose uptake
      in peripheral tissues.

PMID- 19176358
TI  - New insights in covalent modifications of proteins and lipids: phosphorylation
      and beyond.

PMID- 19176360
TI  - JAK1 mutation analysis in T-cell acute lymphoblastic leukemia cell lines.

PMID- 19176359
TI  - The 27-kDa heat shock protein confers cytoprotective effects through a beta 2
      adrenergic receptor agonist-initiated complex with beta-arrestin.
AB  - Heat shock proteins represent an emerging model for the coordinated, multistep
      regulation of apoptotic signaling events. Although certain aspects of the
      biochemistry associated with heat shock protein cytoprotective effects are known,
      little information is found describing the regulation of heat shock protein
      responses to harmful stimuli. During screening for noncanonical beta adrenergic
      receptor signaling pathways in human urothelial cells, using mass spectroscopy
      techniques, an agonist-dependent interaction with beta-arrestin and the 27-kDa
      heat shock protein was observed in vitro. Formation of this beta-arrestin/Hsp27
      complex in response to the selective beta adrenergic receptor agonist
      isoproterenol, was subsequently confirmed in situ by immunofluorescent
      colocalization studies. Radioligand binding techniques characterized a
      homogeneous population of the beta2 adrenergic receptor subtype expressed on
      these cells. Using terminal deoxynucleotidyl transferase biotin-dUTP nick end
      labeling, immunoblot analysis and quantitation of caspase-3 activity to detect
      apoptosis, preincubation of these cells with isoproterenol was found to be
      sufficient for protection against programmed cell death initiated by
      staurosporine. RNA interference strategies confirmed the necessity for Hsp27 as
      well as both beta-arrestin isoforms to confer this cytoprotective consequence of
      beta adrenergic receptor activation in this cell model. As a result, these
      studies represent the first description of an agonist-dependent relationship
      between a small heat shock protein and beta-arrestin to form a previously unknown
      antiapoptotic "signalosome."

PMID- 19176361
TI  - Donor lymphocyte infusions in amyloid light chain amyloidosis: induction of a
      "graft-versus-plasma cell-dyscrasia effect".

PMID- 19176362
TI  - Expression pattern of XBP1(S) in human B-cell lymphomas.
AB  - The transcription factor XBP1 (X-box-binding protein 1) is essential for plasma
      cell (PC) differentiation and immunoglobulin secretion. XBP1 is widely expressed,
      but its activity is precisely controlled by mRNA splicing in response to
      endoplasmic reticulum (ER) stress. It is the active form of XBP1, XBP1(S), which
      is required for PC differentiation. The relationship between XBP1(S) expression
      and PC differentiation in human tissue and its expression in hematologic
      malignancies has eluded assessment. With a novel antibody, we now define XBP1(S)
      expression in a large series of normal and neoplastic lymphoid tissues. We
      establish that XBP1(S) provides a specific marker of advanced plasma
      differentiation and in lymphoid malignancies is restricted to PC-derived
      neoplasms and plasmablastic diffuse large B-cell lymphomas. XBP1(S) expression
      delineates heterogeneity amongst plasmablastic diffuse large B-cell lymphomas,
      identifying a distinct tumor sub-group. Furthermore, our results establish a
      direct and practical means of assessing ER stress in human tumors.

PMID- 19176363
TI  - A new missense mutation in the L ferritin coding sequence associated with
      elevated levels of glycosylated ferritin in serum and absence of iron overload.
AB  - BACKGROUND: Elevated serum ferritin levels are frequently encountered in clinical
      situations and once iron overload or inflammation has been ruled out, many cases
      remain unexplained. Genetic causes of hyperferritinemia associated to early
      cataract include mutations in the iron responsive element in the 5' untranslated
      region of the L ferritin mRNA, responsible for the hereditary hyperferritinemia
      cataract syndrome. DESIGN AND METHODS: We studied 91 probands with
      hyperferritinemia comprising 25 family cases belonging to families with at least
      two cases of unexplained hyperferritinemia, and 66 isolated cases. In the
      families, we also analyzed 30 relatives. Hyperferritinemia was considered as
      unexplained when transferrin saturation was below 45% and/or serum iron below 25
      mumol/L and/or no tissue iron excess was detected, when inflammation had been
      ruled out and when iron responsive element mutation was absent. We carried out
      sequencing analysis of the FTL gene coding the L ferritin. RESULTS: A novel
      heterozygous p.Thr30Ile mutation in the NH2 terminus of L ferritin subunit was
      identified in 17 probands out of the cohort. The mutation was shown to
      cosegregate with hyperferritinemia in all the 10 families studied. No obvious
      clinical symptom was found associated with the presence of the mutation. This
      unique mutation is associated with an unusually high percentage of ferritin
      glycosylation. CONCLUSIONS: This missense mutation of FTL represents a new cause
      of genetic hyperferritinemia without iron overload. We hypothesized that the
      mutation increases the efficacy of L ferritin secretion by increasing the
      hydrophobicity of the N terminal "A" alpha helix.

PMID- 19176364
TI  - A father and his son with systemic AL amyloidosis.

PMID- 19176365
TI  - Comparative microarray analysis and pulmonary changes in Brown Norway rats
      exposed to ovalbumin and concentrated air particulates.
AB  - The interaction between air particulates and genetic susceptibility has been
      implicated in the pathogenesis of asthma. The overall objective of this study was
      to determine the effects of inhalation exposure to environmentally relevant
      concentrated air particulates (CAPs) on the lungs of ovalbumin (ova) sensitized
      and challenged Brown Norway rats. Changes in gene expression were compared with
      lung tissue histopathology, morphometry, and biochemical and cellular parameters
      in bronchoalveolar lavage fluid (BALF). Ova challenge was responsible for the
      preponderance of gene expression changes, related largely to inflammation. CAPs
      exposure alone resulted in no significant gene expression changes, but CAPs and
      ova-exposed rodents exhibited an enhanced effect relative to ova alone with
      differentially expressed genes primarily related to inflammation and airway
      remodeling. Gene expression data was consistent with the biochemical and cellular
      analyses of the BALF, the pulmonary pathology, and morphometric changes when
      comparing the CAPs-ova group to the air-saline or CAPs-saline group. However, the
      gene expression data were more sensitive than the BALF cell type and number for
      assessing the effects of CAPs and ova versus the ova challenge alone. In
      addition, the gene expression results provided some additional insight into the
      TGF-beta-mediated molecular processes underlying these changes. The broad-based
      histopathology and functional genomic analyses demonstrate that exposure to CAPs
      exacerbates rodents with allergic inflammation induced by an allergen and
      suggests that asthmatics may be at increased risk for air pollution effects.

PMID- 19176366
TI  - Mode of action analysis for the synthetic pyrethroid metofluthrin-induced rat
      liver tumors: evidence for hepatic CYP2B induction and hepatocyte proliferation.
AB  - Two-year treatment with high doses of Metofluthrin produced hepatocellular tumors
      in both sexes of Wistar rats. To understand the mode of action (MOA) by which the
      tumors are produced, a series of studies examined the effects of Metofluthrin on
      hepatic microsomal cytochrome P450 (CYP) content, hepatocellular proliferation,
      hepatic gap junctional intercellular communication (GJIC), oxidative stress and
      apoptosis was conducted after one or two weeks of treatment. The global gene
      expression profile indicated that most genes with upregulated expression with
      Metofluthrin were metabolic enzymes that were also upregulated with
      phenobarbital. Metofluthrin induced CYP2B and increased liver weights associated
      with centrilobular hepatocyte hypertrophy (increased smooth endoplasmic reticulum
      [SER]), and induction of increased hepatocellular DNA replication. CYP2B1 mRNA
      induction by Metofluthrin was not observed in CAR knockdown rat hepatocytes using
      the RNA interference technique, demonstrating that Metofluthrin induces CYP2B1
      through CAR activation. Metofluthrin also suppressed hepatic GJIC and induced
      oxidative stress and increased antioxidant enzymes, but showed no alteration in
      apoptosis. The above parameters related to the key events in Metofluthrin-induced
      liver tumors were observed at or below tumorigenic dose levels. All of these
      effects were reversible upon cessation of treatment. Metofluthrin did not cause
      cytotoxicity or peroxisome proliferation. Thus, it is highly likely that the MOA
      for Metofluthrin-induced liver tumors in rats is through CYP induction and
      increased hepatocyte proliferation, similar to that seen for phenobarbital. Based
      on analysis with the International Life Sciences Institute/Risk Science Institute
      MOA framework, it is reasonable to conclude that Metofluthrin will not have any
      hepatocarcinogenic activity in humans, at least at expected levels of exposure.

PMID- 19176367
TI  - Case study: an evaluation of the human relevance of the synthetic pyrethroid
      metofluthrin-induced liver tumors in rats based on mode of action.
AB  - In recent years, mode of action (MOA) frameworks have been developed through the
      International Life Sciences Institute Risk Science Institute and the
      International Programme on Chemical Safety, including an evaluation of the human
      relevance of the animal MOA data. In the present paper, the MOA for rat liver
      tumors induced by Metofluthrin is first analyzed through this framework based on
      data from studies on Metofluthrin and information on related chemicals from the
      literature. The human relevance of the rat liver carcinogenic response is then
      discussed based upon the human relevance framework. Two-year treatment with high
      dose of Metofluthrin produced hepatocellular tumors in both sexes of the Wistar
      rats. Metofluthrin induced CYP2B (increased smooth endoplasmic reticulum),
      resulted in increased liver weights which were associated with centrilobular
      hepatocyte hypertrophy, and induction of increased hepatocellular DNA
      replications. The above parameters related to the key events in Metofluthrin
      induced liver tumors were observed at or below tumorigenic dose levels.
      Furthermore, CYP2B induction by Metofluthrin was shown to involve activation of
      the constitutive androstane receptor in rat hepatocytes. Based on the evidence,
      including a comparison with the results with another chemical, phenobarbital,
      acting by a similar MOA, it is reasonable to conclude that Metofluthrin will not
      have any hepatocarcinogenic activity in humans.

PMID- 19176369
TI  - Inhibition of class I phosphoinositide 3-kinase activity impairs proliferation
      and triggers apoptosis in acute promyelocytic leukemia without affecting atra
      induced differentiation.
AB  - We have investigated the role of phosphoinositide 3-kinases (PI3Ks) in the in
      vitro pathophysiology of acute promyelocytic leukemia (APL) and in the response
      to treatment with all-trans-retinoic-acid (ATRA), utilizing a range of novel
      inhibitors that target individual or all catalytic class I isoforms of PI3K
      (p110alpha, p110beta, p110delta, and p110gamma). ATRA-induced phosphorylation of
      the Akt kinase and ribosomal S6 protein in APL cells was sensitive to class I
      PI3K, and p110beta or p110delta inhibitors, and to the mammalian target of
      rapamycin (mTOR) inhibitor rapamycin. In primary APL, inhibition of p110beta or
      p110delta triggered apoptosis in the absence or presence of ATRA. Class I PI3K
      inhibition could also reverse ATRA-induced protection of these cells against
      doxorubicin and arsenic trioxide, correlating with impaired induction of the
      antiapoptotic MCL-1 protein. The differentiation-inducing effects of ATRA were
      not dependent on class I PI3K/mTOR. In summary, class I PI3K signaling, mediated
      by p110beta and p110delta, plays an important role in basal and ATRA-induced cell
      survival mechanisms in APL. Addition of PI3K inhibitors to induction treatment
      regimens may provide therapeutic benefit.

PMID- 19176368
TI  - Check Sample Abstracts.
AB  - The following abstracts are compiled from Check Sample exercises published in
      2008. These peer-reviewed case studies assist laboratory professionals with
      continuing medical education and are developed in the areas of clinical
      chemistry, cytopathology, forensic pathology, hematology, microbiology, surgical
      pathology, and transfusion medicine. Abstracts for all exercises published in the
      program will appear annually in AJCP.

PMID- 19176370
TI  - The plexin-A1 receptor activates vascular endothelial growth factor-receptor 2
      and nuclear factor-kappaB to mediate survival and anchorage-independent growth of
      malignant mesothelioma cells.
AB  - The semaphorins and their receptors, the neuropilins and the plexins, are
      constituents of a complex regulatory system that controls axonal guidance.
      Moreover, many types of tumor cells express various members of semaphorins and
      receptors, but the biological activities within tumor mass and the signal
      transduction mechanism(s) they use are largely unknown. Here, we show that in
      asbestos-related malignant pleural mesothelioma (MPM), Semaphorin-6D (Sema6D) and
      its receptor plexin-A1 are frequently expressed and trigger a prosurvival program
      that promotes anchorage-independent growth of MPM cells. Interestingly, the same
      response is also controlled by the tyrosine kinase receptors of vascular
      endothelial growth factor (VEGF) through a nuclear factor-kappaB (NF-kappaB)
      dependent pathway. We found that in MPM cells, plexin-A1 and VEGF-receptor 2
      (VEGF-R2) are associated in a complex. Moreover, the presence of Sema6D promotes
      the tyrosine phosphorylation of VEGF-R2 in a plexin-A1-dependent manner. This is
      necessary for basal and Sema6D-induced NF-kappaB transcriptional activity, and NF
      kappaB mediates tumor cell survival. Expression of Sema6D and plexin-A1 is
      induced by asbestos fibers and overexpression of plexin-A1 in nonmalignant
      mesothelial cells inhibits cell death after asbestos exposure. This work
      identifies a new biological function of semaphorins in cancer cells and suggests
      the involvement of an undescribed survival pathway during MPM tumorigenesis.

PMID- 19176371
TI  - Low-density lipoprotein receptor-related protein 1 promotes cancer cell migration
      and invasion by inducing the expression of matrix metalloproteinases 2 and 9.
AB  - The low-density lipoprotein receptor-related protein 1 (LRP1) is a
      multifunctional endocytic receptor involved in the metabolism of various
      extracellular ligands, including proteinases, that play critical roles in tumor
      invasion. Although several studies have shown an increased expression of LRP1 in
      cancer cells, its function in tumor development and progression remains largely
      unclear. Here, we reveal a novel mechanism by which LRP1 induces the expression
      of matrix metalloproteinase 2 (MMP2) and MMP9 and thereby promotes the migration
      and invasion of human glioblastoma U87 cells. Knockdown of LRP1 expression
      greatly decreased U87 cell migration and invasion, which was rescued by the
      forced expression of a functional LRP1 minireceptor. Inhibition of ligand binding
      to LRP1 by a specific antagonist, receptor-associated protein, also led to
      reduced cancer cell migration and invasion. Because MMPs play critical roles in
      cancer cell migration and invasion, we examined the expression of several MMPs
      and found that the expression of functional MMP2 and MMP9 was selectively
      decreased in LRP1 knockdown cells. More importantly, decreased cell migration and
      invasion of LRP1 knockdown cells were completely rescued by exogenous expression
      of MMP2 or MMP9, suggesting that these MMPs are likely downstream targets of LRP1
      mediated signaling. We further show that the level of phosphorylated
      extracellular signal-regulated kinase (ERK) was significantly decreased in LRP1
      silenced cells, suggesting that ERK is a potential mediator of LRP1-regulated
      MMP2 and MMP9 expression in U87 cells. Together, our data strongly suggest that
      LRP1 promotes glioblastoma cell migration and invasion by regulating the
      expression and function of MMP2 and MMP9 perhaps via an ERK-dependent signaling
      pathway.

PMID- 19176372
TI  - Akt activation synergizes with Trp53 loss in oral epithelium to produce a novel
      mouse model for head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a common human neoplasia with
      poor prognosis and survival that frequently displays Akt overactivation. Here we
      show that mice displaying constitutive Akt activity (myrAkt) in combination with
      Trp53 loss in stratified epithelia develop oral cavity tumors that phenocopy
      human HNSCC. The myrAkt mice develop oral lesions, making it a possible model of
      human oral dysplasia. The malignant conversion of these lesions, which is
      hampered due to the induction of premature senescence, is achieved by the
      subsequent ablation of Trp53 gene in the same cells in vivo. Importantly, mouse
      oral tumors can be followed by in vivo imaging, show metastatic spreading to
      regional lymph nodes, and display activation of nuclear factor-kappaB and signal
      transducer and activator of transcription-3 pathways and decreased transforming
      growth factor-beta type II receptor expression, thus resembling human
      counterparts. In addition, malignant conversion is associated with increased
      number of putative tumor stem cells. These data identify activation of Akt and
      p53 loss as a major mechanism of oral tumorigenesis in vivo and suggest that
      blocking these signaling pathways could have therapeutic implications for the
      management of HNSCC.

PMID- 19176373
TI  - In vivo molecular imaging of cancer with a quenching near-infrared fluorescent
      probe using conjugates of monoclonal antibodies and indocyanine green.
AB  - Near-infrared (NIR) fluorophores have several advantages over visible
      fluorophores, including improved tissue penetration and lower autofluorescence;
      however, only indocyanine green (ICG) is clinically approved. Its use in
      molecular imaging probes is limited because it loses its fluorescence after
      protein binding. This property can be harnessed to create an activatable NIR
      probe. After cell binding and internalization, ICG dissociates from the targeting
      antibody, thus activating fluorescence. ICG was conjugated to the antibodies
      daclizumab (Dac), trastuzumab (Tra), or panitumumab (Pan). The conjugates had
      almost no fluorescence in PBS but became fluorescent after SDS and 2
      mercaptoethanol, with a quenching capacity of 10-fold for 1:1 conjugates and 40-
      to 50-fold for 1:5 conjugates. In vitro microscopy showed activation within the
      endolysosomes in target cells. In vivo imaging in mice showed that CD25
      expressing tumors were specifically visualized with Dac-ICG. Furthermore, tumors
      overexpressing HER1 and HER2 were successfully characterized in vivo by using Pan
      ICG(1:5) and Tra-ICG(1:5), respectively. Thus, we have developed an activatable
      NIR optical probe that "switches on" only in target cells. Because both the
      antibody and the fluorophore are Food and Drug Administration approved, the
      likelihood of clinical translation is improved.

PMID- 19176374
TI  - p21/Cip1 and p27/Kip1 Are essential molecular targets of inositol hexaphosphate
      for its antitumor efficacy against prostate cancer.
AB  - Inositol hexaphosphate (IP6) causes G(1) arrest and increases cyclin-dependent
      kinase inhibitors p21/Cip1 and p27/Kip1 protein levels in human prostate cancer
      (PCa) DU145 cells lacking functional p53. However, whether cyclin-dependent
      kinase inhibitor I induction by IP6 plays any role in its antitumor efficacy is
      unknown. Herein, we observed that either p21 or p27 knockdown by small
      interfering RNA has no considerable effect on IP6-induced G(1) arrest, growth
      inhibition, and death in DU145 cells; however, the simultaneous knockdown of both
      p21 and p27 reversed the effects of IP6. To further confirm these findings both
      in vitro and in vivo, we generated DU145 cell variants with knockdown levels of
      p21 (DU-p21), p27 (DU-p27), or both (DU-p21+p27) via retroviral transduction of
      respective short hairpin RNAs. Knocking down p21 or p27 individually did not
      alter IP6-caused cell growth inhibition and G(1) arrest; however, their
      simultaneous ablation completely reversed the effects of IP6. In tumor xenograft
      studies, IP6 (2% w/v, in drinking water) caused a comparable reduction in tumor
      volume (40-46%) and tumor cell proliferation (26-28%) in DU-EV (control), DU-p21,
      and DU-p27 tumors but lost most of its effect in DU-p21+p27 tumors. IP6-caused
      apoptosis also occurred in a Cip/Kip-dependent manner because DU-p21+p27 cells
      were completely resistant to IP6-induced apoptosis both in cell culture and
      xenograft. Together, these results provide evidence, for the first time, of the
      critical role of p21 and p27 in mediating the anticancer efficacy of IP6, and
      suggest their redundant role in the antiproliferative and proapoptotic effects of
      IP6 in p53-lacking human PCa cells, both in vitro and in vivo.

PMID- 19176375
TI  - Proteasome inhibition blocks ligand-induced dynamic processing and
      internalization of epidermal growth factor receptor via altered receptor
      ubiquitination and phosphorylation.
AB  - Epidermal growth factor (EGF) receptor (EGFR), a member of the EGF superfamily of
      receptor tyrosine kinases, is a critical regulator of cell growth and an
      important target for single agent and combination anticancer therapeutics. To
      further investigate the dynamics of ligand-induced EGFR processing and regulation
      noninvasively, we developed a chimeric EGFR-firefly luciferase (FLuc) fusion
      reporter to directly monitor processing of EGFR in real-time. In a stable HeLa
      cell line expressing the reporter at physiologically relevant levels,
      bioluminescence imaging continuously monitored reporter dynamics, correlating
      with the ligand-induced response of endogenous EGFR as determined by Western
      blot, subcellular localization of an EGFR-green fluorescent protein (GFP) fusion
      protein, and validated pharmacologic responses. The signaling competency of the
      reporter was confirmed by gene rescue experiments in EGFR-null cells.
      Bioluminescence analysis further showed that proteasome inhibition with
      bortezomib or MG132 attenuated overall ligand-induced degradation of EGFR. In
      cells expressing EGFR-GFP, pretreatment with proteasome inhibitors trapped
      essentially all of the receptor at the cell membrane both before and after ligand
      induced activation with EGF. Furthermore, proteasome inhibition enhanced receptor
      ubiquitination in both the basal and ligand-activated states as well as delayed
      the processing of ligand-activated phosphorylation of the receptor, kinetically
      correlating with attenuated receptor degradation. These observations point to a
      potential mechanism for the synergistic therapeutic effects of combination EGFR-
      and proteasome-targeted therapies.

PMID- 19176376
TI  - A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen:
      implications for cancer vaccine design.
AB  - The tumor antigen NY-ESO-1 is a promising cancer vaccine target. We describe here
      a novel HLA-B7-restricted NY-ESO-1 epitope, encompassing amino acids 60-72
      (APRGPHGGAASGL), which is naturally presented by melanoma cells. The tumor
      epitope bound to HLA-B7 by bulging outward from the peptide-binding cleft. This
      bulged epitope was not an impediment to T-cell recognition, however, because four
      of six HLA-B7(+) melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX vaccine
      generated a potent T-cell response to this determinant. Moreover, the response to
      this epitope was immunodominant in three of these patients and, unlike the T-cell
      responses to bulged HLA class I viral epitopes, the responding T cells possessed
      a remarkably broad TCR repertoire. Interestingly, HLA-B7(+) melanoma patients who
      did not receive the NY-ESO-1 ISCOMATRIX vaccine rarely generated a spontaneous T
      cell response to this cryptic epitope, suggesting a lack of priming of such T
      cells in the natural anti-NY-ESO-1 response, which may be corrected by
      vaccination. Together, our results reveal several surprising aspects of antitumor
      immunity and have implications for cancer vaccine design.

PMID- 19176377
TI  - Suppression of cFLIP by lupeol, a dietary triterpene, is sufficient to overcome
      resistance to TRAIL-mediated apoptosis in chemoresistant human pancreatic cancer
      cells.
AB  - Overexpression of cellular FLICE-like inhibitory protein (cFLIP) is reported to
      confer chemoresistance in pancreatic cancer (PaC) cells. This study was designed
      to investigate the effect of lupeol, a dietary triterpene, on (a) apoptosis of
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy-resistant
      PaC cells overexpressing cFLIP and (b) growth of human pancreatic tumor
      xenografts in vivo. The effect of lupeol treatment on proliferation and
      TRAIL/caspase-8/cFLIP machinery in PaC cells was investigated. Next, cFLIP
      overexpressing and cFLIP-suppressed cells were tested for sensitivity to
      recombinant TRAIL therapy in the presence of lupeol. Further, athymic nude mice
      implanted with AsPC-1 cells were treated with lupeol (40 mg/kg) thrice a week and
      surrogate biomarkers were evaluated in tumors. Lupeol alone treatment of cells
      caused (a) decrease in proliferation, (b) induction of caspase-8 and poly(ADP
      ribose) polymerase cleavage, and (c) down-regulation of transcriptional
      activation and expression of cFLIP. Lupeol was observed to increase the TRAIL
      protein level in cells. Lupeol significantly decreased the viability of AsPC-1
      cells both in cFLIP-suppressed cells and in cFLIP-overexpressing cells. Lupeol
      significantly sensitized chemoresistant PaC cells to undergo apoptosis by
      recombinant TRAIL. Finally, lupeol significantly reduced the growth of human PaC
      tumors propagated in athymic nude mice and caused modulation of cFLIP and TRAIL
      protein levels in tumors. Our findings showed the anticancer efficacy of lupeol
      with mechanistic rationale against highly chemoresistant human PaC cells. We
      suggest that lupeol, alone or as an adjuvant to current therapies, could be
      useful for the management of human PaC.

PMID- 19176380
TI  - Prostaglandin E2 stimulates human lung carcinoma cell growth through induction of
      integrin-linked kinase: the involvement of EP4 and Sp1.
AB  - Cyclooxygenase-2-derived prostaglandin E(2) (PGE(2)) stimulates tumor cell growth
      and progression. However, the mechanisms by which PGE(2) increases tumor growth
      remain incompletely understood. In studies performed in non-small cell lung
      carcinoma (NSCLC) cells, we found that PGE(2) stimulates the expression of
      integrin-linked kinase (ILK). ILK small interfering RNA (siRNA) inhibited the
      mitogenic effects of PGE(2). In view of its perceived importance, we turned our
      attention to the mechanisms involved in PGE(2)-induced ILK expression and found
      that this effect was blocked by an antagonist of the PGE(2) receptor subtype EP4
      and by EP4 siRNA. Furthermore, we showed that PGE(2) induction of ILK was
      associated with phosphorylation of extracellular signal-regulated kinase and
      phosphatidylinositol 3-kinase/Akt, which were abrogated by ILK siRNA. Transient
      transfection, gel mobility shift assays, and chromatin immunoprecipitation
      experiments showed that PGE(2) induced ILK promoter activity and increased Sp1,
      although it had no effect on nuclear factor-kappaB and AP-2 DNA-binding activity.
      Blockade of Sp1 abrogated the effect of PGE(2) on expression of ILK and promoter
      activity and on cell growth. In summary, our observations show that PGE(2)
      increases NSCLC cell growth through increased ILK expression, which is dependent
      on EP4 signaling and on induction of Sp1 protein and Sp1 DNA-binding activity in
      the ILK promoter. These studies suggest a novel molecular mechanism by which
      PGE(2) stimulates NSCLC cell growth and unveils a new molecular target for the
      development of therapies against NSCLC.

PMID- 19176379
TI  - Achaete-scute complex homologue 1 regulates tumor-initiating capacity in human
      small cell lung cancer.
AB  - The basic helix-loop-helix transcription factor achaete-scute complex homologue 1
      (ASCL1) is essential for the development of normal lung neuroendocrine cells as
      well as other endocrine and neural tissues. Small cell lung cancer (SCLC) and non
      SCLC with neuroendocrine features express ASCL1, where the factor may play a role
      in the virulence and primitive neuroendocrine phenotype of these tumors. In this
      study, RNA interference knockdown of ASCL1 in cultured SCLC resulted in
      inhibition of soft agar clonogenic capacity and induction of apoptosis. cDNA
      microarray analyses bolstered by expression studies, flow cytometry, and
      chromatin immunoprecipitation identified two candidate stem cell marker genes,
      CD133 and aldehyde dehydrogenase 1A1 (ALDH1A1), to be directly regulated by ASCL1
      in SCLC. In SCLC direct xenograft tumors, we detected a relatively abundant
      CD133(high)-ASCL1(high)-ALDH1(high) subpopulation with markedly enhanced
      tumorigenicity compared with cells with weak CD133 expression. Tumorigenicity in
      the CD133(high) subpopulation depended on continued ASCL1 expression. Whereas
      CD133(high) cells readily reconstituted the range of CD133 expression seen in the
      original xenograft tumor, CD133(low) cells could not. Our findings suggest that a
      broad range of SCLC cells has tumorigenic capacity rather than a small discrete
      population. Intrinsic tumor cell heterogeneity, including variation in key
      regulatory factors such as ASCL1, can modulate tumorigenicity in SCLC.

PMID- 19176381
TI  - Transcriptional switch of dormant tumors to fast-growing angiogenic phenotype.
AB  - Tumor dormancy has important implications for early detection and treatment of
      cancer. Lack of experimental models and limited clinical accessibility constitute
      major obstacles to the molecular characterization of dormant tumors. We have
      developed models in which human tumors remain dormant for a prolonged period of
      time (>120 days) until they switch to rapid growth and become strongly
      angiogenic. These angiogenic tumors retain their ability to grow fast once
      injected in new mice. We hypothesized that dormant tumors undergo a stable
      genetic reprogramming during their switch to the fast-growing phenotype. Genome
      wide transcriptional analysis was done to dissect the molecular mechanisms
      underlying the switch of dormant breast carcinoma, glioblastoma, osteosarcoma,
      and liposarcoma tumors. A consensus expression signature distinguishing all four
      dormant versus switched fast-growing tumors was generated. In alignment with our
      phenotypic observation, the angiogenesis process was the most significantly
      affected functional gene category. The switch of dormant tumors was associated
      with down-regulation of angiogenesis inhibitor thrombospondin and decreased
      sensitivity of angiogenic tumors to angiostatin. The conversion of dormant tumors
      to exponentially growing tumors was also correlated with regulation and
      activation of pathways not hitherto linked to tumor dormancy process, such as
      endothelial cell-specific molecule-1, 5'-ecto-nucleotidase, tissue inhibitor of
      metalloproteinase-3, epidermal growth factor receptor, insulin-like growth factor
      receptor, and phosphatidylinositol 3-kinase signaling. Further, novel dormancy
      specific biomarkers such as H2BK and Eph receptor A5 (EphA5) were discovered.
      EphA5 plasma levels in mice and mRNA levels in tumor specimens of glioma patients
      correlated with diseases stage. These data will be instrumental in identifying
      novel early cancer biomarkers and could provide a rationale for development of
      dormancy-promoting tumor therapy strategies.

PMID- 19176382
TI  - GGAP2/PIKE-a directly activates both the Akt and nuclear factor-kappaB pathways
      and promotes prostate cancer progression.
AB  - GGAP2/PIKE-A is a GTP-binding protein that can enhance Akt activity. Increased
      activation of the AKT and nuclear factor-kappaB (NF-kappaB) pathways have been
      identified as critical steps in cancer initiation and progression in a variety of
      human cancers. We have found significantly increased expression GGAP2 in the
      majority of human prostate cancers and GGAP2 expression increases Akt activation
      in prostate cancer cells. Thus, increased GGAP2 expression is a common mechanism
      for enhancing the activity of the Akt pathway in prostate cancers. In addition,
      we have found that activated Akt can bind and phosphorylate GGAP2 at serine 629,
      which enhances GTP binding by GGAP2. Phosphorylated GGAP2 can bind the p50
      subunit of NF-kappaB and enhances NF-kappaB transcriptional activity. When
      expressed in prostate cancer cells, GGAP2 enhances proliferation, foci formation,
      and tumor progression in vivo. Thus, increased GGAP2 expression, which is present
      in three quarters of human prostate cancers, can activate two critical pathways
      that have been linked to prostate cancer initiation and progression.

PMID- 19176383
TI  - Hyaluronan, CD44, and emmprin regulate lactate efflux and membrane localization
      of monocarboxylate transporters in human breast carcinoma cells.
AB  - Interactions of hyaluronan with CD44 in tumor cells play important cooperative
      roles in various aspects of malignancy and drug resistance. Emmprin (CD147;
      basigin) is a cell surface glycoprotein of the immunoglobulin superfamily that is
      highly up-regulated in malignant cancer cells and stimulates hyaluronan
      production, as well as several downstream signaling pathways. Emmprin also
      interacts with various monocarboxylate transporters (MCT). Malignant cancer cells
      use the glycolytic pathway and require MCTs to efflux lactate that results from
      glycolysis. Glycolysis and lactate secretion contribute to malignant cell
      behaviors and drug resistance in tumor cells. In the present study, we find that
      perturbation of endogenous hyaluronan, using small hyaluronan oligosaccharides,
      rapidly inhibits lactate efflux from breast carcinoma cells; down-regulation of
      emmprin, using emmprin small interfering RNA, also results in decreased efflux.
      In addition, we find that CD44 coimmunoprecipitates with MCT1, MCT4, and emmprin
      and colocalizes with these proteins at the plasma membrane. Moreover, after
      treatment of the cells with hyaluronan oligosaccharides, CD44, MCT1, and MCT4
      become localized intracellularly whereas emmprin remains at the cell membrane.
      Together, these data indicate that constitutive interactions among hyaluronan,
      CD44, and emmprin contribute to regulation of MCT localization and function in
      the plasma membrane of breast carcinoma cells.

PMID- 19176384
TI  - Cyclic AMP signaling as a mediator of vasculogenic mimicry in aggressive human
      melanoma cells in vitro.
AB  - Aggressive melanoma cells can engage in a process termed vasculogenic mimicry
      (VM) that reflects the ability of tumor cells to express a multipotent, stem cell
      like phenotype. Melanoma cell plasticity contributes to the lack of efficient
      therapeutic strategies targeting metastatic tumors. This study reveals cyclic AMP
      as a mediator of VM in vitro. In uveal and cutaneous metastatic aggressive human
      melanoma cells, an increase in cyclic AMP by forskolin, dibutyryl cyclic AMP, or
      G protein-coupled receptor (GPCR) ligands such as adrenaline and vasoactive
      intestinal peptide inhibited VM to different extents. Although chemical
      modulators of protein kinase A (PKA) had no effect, a specific pharmacologic
      activator of Exchange protein directly activated by cyclic AMP (Epac) impaired
      VM. Ras-associated protein-1 (Rap1) activation assays revealed that cyclic AMP
      elevating agents induce a PKA-independent activation of Epac/Rap1. Pharmacologic
      inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activity
      abolished VM. Phosphorylation of ERK1/2 was PKA-independently inhibited by
      forskolin but not inhibited by Epac/Rap1 signaling, PKA modulation, or GPCR
      ligands. Furthermore, the forskolin also inhibited phosphatidyl inositol-3-kinase
      (PI3K)-mediated activation of protein kinase Akt, as monitored by Ser473
      phosphorylation. The pharmacologic activation of Epac and GPCR ligands slightly
      stimulated Akt, a likely concomitant process of VM modulation. Collectively,
      these data show that forskolin strongly inhibits VM through PKA-independent
      activation of Epac/Rap1, PKA-, and Epac-independent inactivation of ERK1/2 and
      inhibition of PI3K/Akt. The data also show that VM inhibition by GPCR ligands
      involves mainly the Epac/Rap1-activated signal. Thus cyclic AMP inhibits VM
      through multiple signaling pathways.

PMID- 19176385
TI  - Curcumin disrupts the Mammalian target of rapamycin-raptor complex.
AB  - Curcumin (diferuloylmethane), a polyphenol natural product of the plant Curcuma
      longa, is undergoing early clinical trials as a novel anticancer agent. However,
      the anticancer mechanism of curcumin remains to be elucidated. Recently, we have
      shown that curcumin inhibits phosphorylation of p70 S6 kinase 1 (S6K1) and
      eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), two
      downstream effector molecules of the mammalian target of rapamycin complex 1
      (mTORC1) in numerous cancer cell lines. This study was designed to elucidate the
      underlying mechanism. We observed that curcumin inhibited mTORC1 signaling not by
      inhibition of the upstream kinases, such as insulin-like growth factor 1 receptor
      (IGF-IR) and phosphoinositide-dependent kinase 1 (PDK1). Further, we found that
      curcumin inhibited mTORC1 signaling independently of protein phosphatase 2A
      (PP2A) or AMP-activated protein kinase AMPK-tuberous sclerosis complex (TSC).
      This is evidenced by the findings that curcumin was able to inhibit
      phosphorylation of S6K1 and 4E-BP1 in the cells pretreated with PP2A inhibitor
      (okadaic acid) or AMPK inhibitor (compound C), or in the cells expressing
      dominant-negative (dn) PP2A, shRNA to PP2A-A subunit, or dn-AMPKalpha. Curcumin
      did not alter the TSC1/2 interaction. Knockout of TSC2 did not affect curcumin
      inhibition of mTOR signaling. Finally, we identified that curcumin was able to
      dissociate raptor from mTOR, leading to inhibition of mTORC1 activity. Therefore,
      our data indicate that curcumin may represent a new class of mTOR inhibitor.

PMID- 19176386
TI  - Histone deacetylases are required for androgen receptor function in hormone
      sensitive and castrate-resistant prostate cancer.
AB  - Transcriptional activity of the androgen receptor (AR) is crucial for growth and
      survival of prostate cancer even upon development of resistance to androgen
      ablation and antiandrogen therapies. Therefore, novel therapies that can suppress
      AR transcriptional activity when conventional hormone therapies fail are needed.
      Here, we show that histone deacetylase (HDAC) inhibitors, including SAHA
      (vorinostat) and LBH589, which are currently being tested in clinic, could be
      such a therapy. HDAC inhibitors block the AR-mediated transcriptional activation
      of many genes, including the TMPRSS2 gene involved in fusion with ETS family
      members in a majority of prostate cancers. Genetic knockdown of either HDAC1 or
      HDAC3 can also suppress expression of AR-regulated genes, recapitulating the
      effect of HDAC inhibitor treatment. Whereas HDAC inhibitor treatment can lower
      androgen receptor protein levels in prostate cancer cells, we show that
      independent of AR protein levels, HDAC inhibitors block AR activity through
      inhibiting the assembly of coactivator/RNA polymerase II complex after AR binds
      to the enhancers of target genes. Failed complex assembly is associated with a
      phase shift in the cyclical wave of AR recruitment that typically occurs in
      response to ligand treatment. HDAC inhibitors retain the ability to block AR
      activity in castration-resistant prostate cancer models and, therefore, merit
      clinical investigation in this setting. The HDAC-regulated AR target genes
      defined here can serve as biomarkers to ensure sufficient levels of HDAC
      inhibition.

PMID- 19176387
TI  - A multiscale mathematical model for oncolytic virotherapy.
AB  - One of the most promising strategies to treat cancer is attacking it with
      viruses. Oncolytic viruses can kill tumor cells specifically or induce anticancer
      immune response. A multiscale model for virotherapy of cancer is investigated
      through simulations. It was found that, for intratumoral virus administration, a
      solid tumor can be completely eradicated or keep growing after a transient
      remission. Furthermore, the model reveals undamped oscillatory dynamics of tumor
      cells and virus populations, which demands new in vivo and in vitro quantitative
      experiments aiming to detect this oscillatory response. The conditions for which
      each one of the different tumor responses dominates, as well as the occurrence
      probabilities for the other nondominant therapeutic outcomes, were determined.
      From a clinical point of view, our findings indicate that a successful, single
      agent virotherapy requires a strong inhibition of the host immune response and
      the use of potent virus species with a high intratumoral mobility. Moreover, due
      to the discrete and stochastic nature of cells and their responses, an optimal
      range for viral cytotoxicity is predicted because the virotherapy fails if the
      oncolytic virus demands either a too short or a very large time to kill the tumor
      cell. This result suggests that the search for viruses able to destroy tumor
      cells very fast does not necessarily lead to a more effective control of tumor
      growth.

PMID- 19176388
TI  - A destructive cascade mediated by CCL2 facilitates prostate cancer growth in
      bone.
AB  - Monocyte chemoattractant protein 1 (CCL2) is a recently identified prominent
      regulator of prostate cancer growth and metastasis. The purpose of this study was
      to investigate the mechanistic role of CCL2 in prostate cancer growth in bone.
      The present study found that CCL2 was up-regulated in osteoblasts (3-fold by PC-3
      and 2-fold by VCaP conditioned medium) and endothelial cells (2-fold by PC-3 and
      VCaP conditioned medium). Parathyroid hormone-related protein (PTHrP) treatment
      of osteoblastic cells up-regulated CCL2 and was blocked by a PTHrP antagonist,
      suggesting that prostate cancer-derived PTHrP plays an important role in
      elevation of osteoblast-derived CCL2. CCL2 indirectly increased blood vessel
      formation in endothelial cells through vascular endothelial growth factor-A,
      which was up-regulated 2-fold with administration of CCL2 in prostate cancer
      cells. In vivo, anti-CCL2 treatment suppressed tumor growth in bone. The
      decreased tumor burden was associated with decreased bone resorption (serum
      TRAP5b levels were decreased by 50-60% in anti-CCL2-treated animals from VCaP or
      PC-3 cell osseous lesions) and microvessel density was decreased by 70% in anti
      CCL2-treated animals with bone lesions from VCaP cells. These data suggest that a
      destructive cascade is driven by tumor cell-derived, PTHrP-mediated induction of
      CCL2, which facilitates tumor growth via enhanced osteoclastic and endothelial
      cell activity in bone marrow. Taken together, CCL2 mediates the interaction
      between tumor-derived factors and host-derived chemokines acting in cooperation
      to promote skeletal metastasis.

PMID- 19176389
TI  - Distinct roles of BARD1 isoforms in mitosis: full-length BARD1 mediates Aurora B
      degradation, cancer-associated BARD1beta scaffolds Aurora B and BRCA2.
AB  - The BRCA1-associated ring domain protein 1 (BARD1) interacts with BRCA1 via its
      RING finger domain. The BARD1-BRCA1 complex participates in DNA repair, cell
      cycle control, genomic stability, and mitotic spindle formation through its E3
      ubiquitin ligase activity. Cancer cells express several BARD1 protein isoforms,
      including the RING finger-deficient variant BARD1beta. Here, we show that BARD1
      has BRCA1-dependent and BRCA1-independent functions in mitosis. BARD1, but not
      BRCA1, localizes to the midbody at telophase and cytokinesis, where it
      colocalizes with Aurora B. The 97-kDa full-length (FL) BARD1 coimmunoprecipates
      with BRCA1, but the 82-kDa BARD1beta coimmunoprecipitates with Aurora B and
      BRCA2. We used selective small interfering RNAs to distinguish the functions of
      FL BARD1 and BARD1beta. Depletion of FL BARD1 had only minor effects on cell
      growth and did not abolish midbody localization of BARD1 staining, but resulted
      in massive up-regulation of Aurora B. In contrast, suppression of FL BARD1 and
      BARD1beta led to growth arrest and correlated with various mitotic defects and
      disappearance of midbody localization of BARD1 staining. Our data suggest a novel
      function of FL BARD1 in Aurora B ubiquitination and degradation, opposing a
      proproliferative function of BARD1beta in scaffolding Aurora B and BRCA2. Thus,
      loss of FL BARD1 and up-regulation of Aurora B, as observed in cancer cells, can
      be explained by an imbalance of FL BARD1 and BARD1beta.

PMID- 19176390
TI  - A gonadotropin-releasing hormone-II antagonist induces autophagy of prostate
      cancer cells.
AB  - Gonadotropin-releasing hormone-I (GnRH-I) is known to directly regulate prostate
      cancer cell proliferation. However, the role of GnRH-II in prostate cancer is
      unclear. Here, we investigated the effect of the GnRH-II antagonist trptorelix-1
      (Trp-1) on growth of PC3 prostate cancer cells. Trp-1 induced growth inhibition
      of PC3 cells in vitro and inhibited growth of PC3 cells xenografted into nude
      mice. FITC-N3, an FITC-conjugated Trp-1 analogue, was largely present in the
      mitochondria of prostate cancer cells, but not in other cells that are not
      derived from the prostate. Trp-1-induced PC3 growth inhibition was associated
      with decreased mitochondrial membrane potential and increased levels of
      mitochondrial and cytosolic reactive oxygen species (ROS). Growth inhibition was
      partially prevented by cotreating cells with N-acetyl cysteine, an antioxidant.
      Cytochrome c release and caspase-3 activation were not detected in Trp-1-treated
      cells. However, Trp-1 induced autophagosome formation, as seen by increased
      LysoTracker staining and recruitment of microtubule-associated protein 1 light
      chain 3 to these new lysosomal compartments. Trp-1-induced autophagy was
      accompanied by decreased AKT phosphorylation and increased c-Jun NH(2) terminal
      kinase phosphorylation, two events known to be linked to autophagy. Taken
      together, these data suggest that Trp-1 directly induces mitochondrial
      dysfunction and ROS increase, leading to autophagy of prostate cancer cells. GnRH
      II antagonists may hold promise in the treatment of prostate cancer.

PMID- 19176391
TI  - Translymphatic chemotherapy by intrapleural placement of gelatin sponge
      containing biodegradable Paclitaxel colloids controls lymphatic metastasis in
      lung cancer.
AB  - As a means of treating lymphatic metastasis from lung cancer, the
      pharmacokinetics and therapeutic effects of an intrapleural (ipl) implantable
      drug delivery system consisting of a gelatin sponge impregnated with polylactide
      co-glycolide paclitaxel (PLGA-PTX) microspheres were studied. PLGA-PTX with 7%
      (w/w) drug loading were incorporated into gelatin matrix. The pharmacokinetics
      were studied in rats with one of the following regimens: (a) Taxol 8 mg/kg by
      i.v. injection; (b) Taxol 8 mg/kg ipl; (c) PLGA-PTX (100 mg/kg) ipl; (d) sponge
      containing PLGA-PTX (100 mg/kg) ipl. PTX concentrations in lymph node and plasma
      were determined by liquid chromatography mass spectrometry, and the area under
      the curve (AUC) was calculated. Therapeutic efficacy was assessed in an
      orthotopic lung cancer model with tumor resection 14 days following tumor
      implantation. Animals were randomized to ipl placement of PLGA-PTX sponge,
      placebo sponge, or no treatment. Lymph node metastases were examined at 32 d. The
      results show that the mediastinal lymph node AUC was significantly higher with
      ipl. placement of PLGA-PTX sponge compared with i.v. and ipl administration of
      Taxol. This represents 100- to 400-fold increase of lymphatic drug exposure
      compared with i.v. dosing. Peak plasma concentration was significantly reduced in
      the PLGA-PTX sponge group compared with i.v. dosing. PLGA-PTX particles were
      microscopically identified in lymphatic tissue and resulted in an 80% reduction
      of lymphatic metastasis compared with controls. Translymphatic-targeted drug
      delivery significantly decreases lymphatic metastasis in an orthotopic lung
      cancer model. This effect may be attributable to the improved distribution of PTX
      to the lymphatic system.

PMID- 19176392
TI  - The iron chelator Dp44mT causes DNA damage and selective inhibition of
      topoisomerase IIalpha in breast cancer cells.
AB  - Di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) is being developed
      as an iron chelator with selective anticancer activity. We investigated the
      mechanism whereby Dp44mT kills breast cancer cells, both as a single agent and in
      combination with doxorubicin. Dp44mT alone induced selective cell killing in the
      breast cancer cell line MDA-MB-231 when compared with healthy mammary epithelial
      cells (MCF-12A). It induces G(1) cell cycle arrest and reduces cancer cell
      clonogenic growth at nanomolar concentrations. Dp44mT, but not the iron chelator
      desferal, induces DNA double-strand breaks quantified as S139 phosphorylated
      histone foci (gamma-H2AX) and Comet tails induced in MDA-MB-231 cells.
      Doxorubicin-induced cytotoxicity and DNA damage were both enhanced significantly
      in the presence of low concentrations of Dp44mT. The chelator caused selective
      poisoning of DNA topoisomerase IIalpha (top2alpha) as measured by an in vitro DNA
      cleavage assay and cellular topoisomerase-DNA complex formation. Heterozygous
      Nalm-6 top2alpha knockout cells (top2alpha(+/-)) were partially resistant to
      Dp44mT-induced cytotoxicity compared with isogenic top2alpha(+/+) or top2beta(-/
      ) cells. Specificity for top2alpha was confirmed using top2alpha and top2beta
      small interfering RNA knockdown in HeLa cells. The results show that Dp44mT is
      cytotoxic to breast cancer cells, at least in part, due to selective inhibition
      of top2alpha. Thus, Dp44mT may serve as a mechanistically unique treatment for
      cancer due to its dual ability to chelate iron and inhibit top2alpha activity.

PMID- 19176393
TI  - Comment re: Ran-GTP control of tumor cell mitosis.

PMID- 19176394
TI  - p34SEI-1 inhibits apoptosis through the stabilization of the X-linked inhibitor
      of apoptosis protein: p34SEI-1 as a novel target for anti-breast cancer
      strategies.
AB  - The p34(SEI-1) protein exerts oncogenic effects via regulation of the cell cycle,
      which occurs through a direct interaction with cyclin-dependent kinase 4. Such
      regulation can increase the survival of various types of tumor cells. Here, we
      show that the antiapoptotic function of p34(SEI-1) increases tumor cell survival
      by protecting the X-linked inhibitor of apoptosis protein (XIAP) from
      degradation. Our findings show that p34(SEI-1) inhibits apoptosis. This
      antiapoptotic effect was eliminated by the suppression of p34(SEI-1) expression.
      We also determined that direct binding of p34(SEI-1) to the BIR2 domain prevents
      ubiquitination of XIAP. Interestingly, p34(SEI-1) expression is absent or weak in
      normal tissues but is strongly expressed in tissues obtained from patients with
      breast cancer. Furthermore, the expression levels of p34(SEI-1) and XIAP seem to
      be coordinated in human breast cancer cell lines and tumor tissues. Thus, our
      findings reveal that p34(SEI-1) uses a novel apoptosis-inhibiting mechanism to
      stabilize XIAP.

PMID- 19176396
TI  - Prediction of clinical outcome in multiple lung cancer cohorts by integrative
      genomics: implications for chemotherapy selection.
AB  - The role of adjuvant chemotherapy in patients with stage IB non-small-cell lung
      cancer (NSCLC) is controversial. Identifying patient subgroups with the greatest
      risk of relapse and, consequently, most likely to benefit from adjuvant treatment
      thus remains an important clinical challenge. Here, we hypothesized that
      recurrent patterns of genomic amplifications and deletions in lung tumors could
      be integrated with gene expression information to establish a robust predictor of
      clinical outcome in stage IB NSCLC. Using high-resolution microarrays, we
      generated tandem DNA copy number and gene expression profiles for 85 stage IB
      lung adenocarcinomas/large cell carcinomas. We identified specific copy number
      alterations linked to relapse-free survival and selected genes within these
      regions exhibiting copy number-driven expression to construct a novel integrated
      signature (IS) capable of predicting clinical outcome in this series (P = 0.02).
      Importantly, the IS also significantly predicted clinical outcome in two other
      independent stage I NSCLC cohorts (P = 0.003 and P = 0.025), showing its
      robustness. In contrast, a more conventional molecular predictor based solely on
      gene expression, while capable of predicting outcome in the initial series,
      failed to significantly predict outcome in the two independent data sets. Our
      results suggest that recurrent copy number alterations, when combined with gene
      expression information, can be successfully used to create robust predictors of
      clinical outcome in early-stage NSCLC. The utility of the IS in identifying early
      stage NSCLC patients as candidates for adjuvant treatment should be further
      evaluated in a clinical trial.

PMID- 19176397
TI  - The hypoxia-activated ProDrug AQ4N penetrates deeply in tumor tissues and
      complements the limited distribution of mitoxantrone.
AB  - Hypoxic tumor cells are likely to be resistant to conventional chemotherapy, in
      large part because many anticancer drugs are unable to penetrate into poorly
      oxygenated tumor tissue. Here, we used quantitative immunofluorescence to study
      the distribution of mitoxantrone and AQ4N in tumor tissue. AQ4N is a prodrug
      activated under hypoxic conditions to AQ4, which is structurally similar to
      mitoxantrone and inhibits topoisomerase II. We characterized the penetration of
      mitoxantrone and AQ4N/AQ4 through multilayered cell cultures (MCC) and in
      relation to blood vessels and hypoxic regions in human tumor xenografts. We also
      studied tumor growth delay after treatment with each agent alone and with the
      combination. In both MCC and xenografts, mitoxantrone is taken up by proximal
      cells and penetrates slowly to distant regions. In contrast, AQ4N rapidly
      penetrates MCC and tumor tissue in vivo, and AQ4N (or its reduced form AQ4) is
      detected at high concentration within hypoxic regions. The targeting of
      mitoxantrone to oxygenated regions and AQ4N/AQ4 to hypoxic tumor regions results
      in effective drug exposure over the entire tumor after combined treatment and
      increases tumor growth delay compared with either drug alone. The combination of
      a clinically used anticancer drug with limited tissue penetration and a
      structurally related drug activated in regions of tumor hypoxia is an effective
      strategy to overcome chemoresistance due to the tumor microenvironment. This
      study supports clinical evaluation of AQ4N in combination with conventional
      anticancer agents, such as mitoxantrone.

PMID- 19176395
TI  - Vasculostatin inhibits intracranial glioma growth and negatively regulates in
      vivo angiogenesis through a CD36-dependent mechanism.
AB  - Angiogenesis is a critical physiologic process that is appropriated during
      tumorigenesis. Little is known about how this process is specifically regulated
      in the brain. Brain angiogenesis inhibitor-1 (BAI1) is a brain-predominant seven
      transmembrane protein that contains five antiangiogenic thrombospondin type-1
      repeats (TSR). We recently showed that BAI1 is cleaved at a conserved proteolytic
      cleavage site releasing a soluble, 120 kDa antiangiogenic factor called
      vasculostatin (Vstat120). Vstat120 has been shown to inhibit in vitro
      angiogenesis and suppress subcutaneous tumor growth. Here, we examine its effect
      on the intracranial growth of malignant gliomas and further study its antitumor
      mechanism. First, we show that expression of Vstat120 strongly suppresses the
      intracranial growth of malignant gliomas, even in the presence of the strong
      proangiogenic stimulus mediated by the oncoprotein epidermal growth factor
      receptor variant III (EGFRvIII). This tumor-suppressive effect is accompanied by
      a decrease in tumor vascular density, suggesting a potent antiangiogenic effect
      in the brain. Second, and consistent with this interpretation, we find that
      treatment with Vstat120 reduces the migration of cultured microvascular
      endothelial cells in vitro and inhibits corneal angiogenesis in vivo. Third, we
      show that these antivascular effects critically depend on the presence of the
      cell surface receptor CD36 on endothelial cells in vitro and in vivo, supporting
      the role of Vstat120 TSRs in mediating these effects. These results advance the
      understanding of brain-specific angiogenic regulation, and suggest that Vstat120
      has therapeutic potential in the treatment of brain tumors and other
      intracerebral vasculopathies.

PMID- 19176398
TI  - Expression and functions of transmembrane mucin MUC13 in ovarian cancer.
AB  - MUC13, a transmembrane mucin, is normally expressed in gastrointestinal and
      airway epithelium. Its aberrant expression has been correlated with gastric colon
      and cancer. However, the expression and functions of MUC13 in ovarian cancer are
      unknown. In the present study, the expression profile and functions of MUC13 were
      analyzed to elucidate its potential role in ovarian cancer diagnosis and
      pathogenesis. A recently generated monoclonal antibody (clone PPZ0020) was used
      to determine the expression profile of MUC13 by immunohistochemistry using
      ovarian cancer tissue microarrays and 56 additional epithelial ovarian cancer
      (EOC) samples. The expression of MUC13 was significantly (P < 0.005) higher in
      cancer samples compared with the normal ovary/benign tissues. Among all ovarian
      cancer types, MUC13 expression was specifically present in EOC. For the
      functional analyses, a full-length MUC13 gene cloned in pcDNA3.1 was expressed in
      a MUC13 null ovarian cancer cell line, SKOV-3. Here, we show that the exogenous
      MUC13 expression induced morphologic changes, including scattering of cells.
      These changes were abrogated through c-Jun NH(2) kinase (JNK) chemical inhibitor
      (SP600125) or JNK2 siRNA. Additionally, a marked reduction in cell-cell adhesion
      and significant (P < 0.05) increases in cell motility, proliferation, and
      tumorigenesis in a xenograft mouse model system were observed upon exogenous
      MUC13 expression. These cellular characteristics were correlated with up
      regulation of HER2, p21-activated kinase 1, and p38 protein expression. Our
      findings show the aberrant expression of MUC13 in ovarian cancer and that its
      expression alters the cellular characteristics of SKOV-3 cells. This implies a
      significant role of MUC13 in ovarian cancer.

PMID- 19176399
TI  - Targeting heat shock protein 90 overrides the resistance of lung cancer cells by
      blocking radiation-induced stabilization of hypoxia-inducible factor-1alpha.
AB  - Hypoxia-inducible factor-1 (HIF-1) has been suggested to play a major role in
      tumor radioresistance. However, the mechanisms through which irradiation
      regulates HIF-1alpha expression remain unclear. The purpose of this study was to
      investigate the mechanisms that mediate HIF-1 activation and thus
      radioresistance. Here, we show that irradiation induces survival and angiogenic
      activity in a subset of radioresistant lung cancer cell lines by elevating HIF
      1alpha protein expression. Radiation induced HIF-1alpha protein expression mainly
      through two distinct pathways, including an increase in de novo protein synthesis
      via activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of
      rapamycin (mTOR) and stabilization of HIF-1alpha protein via augmenting the
      interaction between heat shock protein 90 (Hsp90) and HIF-1alpha protein. Whereas
      the PI3K/Akt/mTOR pathway was activated by irradiation in all the lung cancer
      cells examined, the Hsp90-HIF-1alpha interaction was enhanced in the resistant
      cells only. Inhibition of Hsp90 function by 17-allylamino-17
      demethoxygeldanamycin or deguelin, a novel natural inhibitor of Hsp90, suppressed
      increases in HIF-1alpha/Hsp90 interaction and HIF-1alpha expression in
      radioresistant cells. Furthermore, combined treatment of radiation with deguelin
      significantly decreased the survival and angiogenic potential of radioresistant
      lung cancer cells in vitro. We finally determined in vivo that systemic
      administration of deguelin resulted in profound inhibition of tumor growth and
      angiogenesis when combined with radiation. These results provide a strong
      rationale to target Hsp90 as a means to block radiation-induced HIF-1alpha and
      thus to circumvent radioresistance in lung cancer cells.

PMID- 19176400
TI  - Signal transducers and activators of transcription mediate fibroblast growth
      factor-induced vascular endothelial morphogenesis.
AB  - The fibroblast growth factors (FGF) play diverse roles in development, wound
      healing, and angiogenesis. The intracellular signal transduction pathways, which
      mediate these pleiotropic activities, remain incompletely understood. We show
      here that the proangiogenic factors FGF2 and FGF8b can activate signal
      transducers and activators of transcription (STAT) in mouse microvascular
      endothelial cells (EC). Both FGF2 and FGF8b activate STAT5 and to a lesser extent
      STAT1, but not STAT3. The FGF2-dependent activation of endothelial STAT5 was
      confirmed in vivo with the Matrigel plug angiogenesis assay. In tissue samples of
      human gliomas, a tumor type wherein FGF-induced angiogenesis is important, STAT5
      is detected in tumor vessel EC nuclei, consistent with STAT5 activation. By
      forced expression of constitutively active or dominant-negative mutant STAT5A in
      mouse brain ECs, we further show that STAT5 activation is both necessary and
      sufficient for FGF-induced cell migration, invasion, and tube formation, which
      are key events in vascular endothelial morphogenesis and angiogenesis. In
      contrast, STAT5 is not required for brain EC mitogenesis. The cytoplasmic
      tyrosine kinases Src and Janus kinase 2 (Jak2) both seem to be involved in the
      activation of STAT5, as their inhibition reduces FGF2- and FGF8b-induced STAT5
      phosphorylation and EC tube formation. Constitutively active STAT5A partially
      restores tube formation in the presence of Src or Jak2 inhibitors. These
      observations show that FGFs use distinct signaling pathways to induce angiogenic
      phenotypes. Together, our findings implicate the FGF-Jak2/Src-STAT5 cascade as a
      critical angiogenic FGF signaling pathway.

PMID- 19176401
TI  - Ghrelin does not predict adaptive hyperphagia in patients with short bowel
      syndrome.
AB  - BACKGROUND: Adaptive hyperphagia is associated with reduced dependence on
      parenteral nutrition in patients with short bowel syndrome, but mechanisms have
      not been described. Ghrelin (GHR) has orexigenic effects, whereas peptide YY
      (PYY) reduces intake. GHR also acts as a hormone to control body fat stores. The
      authors evaluated whether GHR or PYY was related to caloric intake or absorption
      in patients with short bowel syndrome and whether GHR was associated with body
      mass index. METHODS: Patients were admitted twice for nutrient balance. Height
      and body weight were obtained using standardized protocols. Energy intake > 40
      kcal/kg/day was defined as adaptive hyperphagia. Fasting plasma PYY and GHR were
      assayed in duplicate with Linco enzyme-linked immunosorbent assay kits. RESULTS:
      The median age of the 7 study participants was 62 (range, 45-66) years, time with
      short bowel syndrome was 6.6 (range, 2-29) years, and body mass index was 21.2
      kg/m(2) (range, 19-27.7). Five patients had adaptive hyperphagia. Neither GHR nor
      PYY was significantly related to energy intake or absorption (GHR: R = 0.22 and R
      = -0.233, PYY: R = 0.10 and R = -0.13). Body mass index trended toward an inverse
      association with GHR (GHR: R = -0.540, P = .211). CONCLUSION: The rigorous
      adaptive hyperphagia seen in these patients with short bowel syndrome was not
      related to fasting GHR or PYY, suggesting the need to explore other mechanisms.

PMID- 19176403
TI  - A meta-analysis of aerobic exercise interventions for women with breast cancer.
AB  - The purpose of this meta-analysis was to examine the effectiveness of aerobic
      exercise interventions on cardiopulmonary function and body composition in women
      with breast cancer. Of 24 relevant studies reviewed, 10 studies (N = 588) met the
      inclusion criteria. The findings indicated that aerobic exercise significantly
      improved cardiopulmonary function as assessed by absolute VO2 peak (standardized
      mean difference [SMD] .916, p < .001), relative VO2 peak (SMD .424, p < .05), and
      12-minute walk test ( SMD .502, p < .001). Similarly, aerobic exercise
      significantly improved body composition as assessed by percentage body fat (SMD 
      .890, p < .001), but body weight and lean body mass did not change significantly.
      Aerobic exercise during or after cancer adjuvant therapy seems to be an effective
      means of improving cardiopulmonary function and decreasing percentage body fat in
      women with breast cancer. Further studies are needed to examine the long-term
      benefits of aerobic exercise.

PMID- 19176402
TI  - Balance of Irgm protein activities determines IFN-gamma-induced host defense.
AB  - The immunity-related GTPases (IRG), also known as p47 GTPases, are a family of
      proteins that are tightly regulated by IFNs at the transcriptional level and
      serve as key mediators of IFN-regulated resistance to intracellular bacteria and
      protozoa. Among the IRG proteins, loss of Irgm1 has the most profound impact on
      IFN-gamma-induced host resistance at the physiological level. Surprisingly, the
      losses of host resistance seen in the absence of Irgm1 are sometimes more
      striking than those seen in the absence of IFN-gamma. In the current work, we
      address the underlying mechanism. We find that in several contexts, another
      protein in the IRG family, Irgm3, functions to counter the effects of Irgm1. By
      creating mice that lack Irgm1 and Irgm3, we show that several phenotypes
      important to host resistance that are caused by Irgm1 deficiency are reversed by
      coincident Irgm3 deficiency; these include resistance to Salmonella typhimurium
      in vivo, the ability to affect IFN-gamma-induced Salmonella killing in isolated
      macrophages, and the ability to regulate macrophage adhesion and motility in
      vitro. Other phenotypes that are caused by Irgm1 deficiency, including
      susceptibility to Toxoplasma gondii and the regulation of GKS IRG protein
      expression and localization, are not reversed but exacerbated when Irgm3 is also
      absent. These data suggest that members of the Irgm subfamily within the larger
      IRG family possess activities that can be opposing or cooperative depending on
      the context, and it is the balance of these activities that is pivotal in
      mediating IFN-gamma-regulated host resistance.

PMID- 19176404
TI  - Nurse faculty perceptions of simulation use in nursing education.
AB  - In this study nursing faculty perceptions of the implementation of simulation in
      schools of nursing across Ontario, Canada, were explored using the Q-methodology
      technique. Following Q-methodology guidelines, 104 statements were collected from
      faculty and students with exposure to simulation to determine the concourse (what
      people say about the issue). The statements were classified into six domains,
      including teaching and learning, access/reach, communication, technical features,
      technology set-up and training, and comfort/ease of use with technology. They
      were then refined into 43 final statements for the Q-sample. Next, 28 faculty
      from 17 nursing schools participated in the Q-sorting process. A by-person factor
      analysis of the Q-sort was conducted to identify groups of participants with
      similar viewpoints. Results revealed four major viewpoints held by faculty
      including: (a) Positive Enthusiasts, (b) Traditionalists, (c) Help Seekers, and
      (d) Supporters. In conclusion, simulation was perceived to be an important
      element in nursing education. Overall, there was a belief that clinical
      simulation requires (a) additional support in terms of the time required to
      engage in teaching using this modality, (b) additional human resources to support
      its use, and (c) other types of support such as a repository of clinical
      simulations to reduce the time from development of a scenario to implementation.
      Few negative voices were heard. It was evident that with correct support (human
      resources) and training, many faculty members would embrace clinical simulation
      because it could support and enhance nursing education.

PMID- 19176406
TI  - The Thresholds-Dartmouth partnership and research on shared decision making.
AB  - Thresholds Rehabilitation Centers is one of the largest providers of psychiatric
      rehabilitation services in the United States, and the Dartmouth Psychiatric
      Research Center is a highly regarded team of rehabilitation researchers. This
      column describes efforts to build upon the long-standing collaborative
      relationship between Thresholds (community partner) and Dartmouth (academic
      partner) to implement and study shared decision making in a community mental
      health care setting that serves an ethnoracially diverse population. Shared
      decision making encompasses a client-centered approach in which client and
      practitioner are equal partners. This joint project incorporates modern
      information technology, decision science, cultural competence, stakeholder
      collaboration, outcomes research, and training. The partnership itself provides
      an exemplar of shared decision making.

PMID- 19176407
TI  - My mother's schizophrenia: what I didn't know helped me.

PMID- 19176408
TI  - Premature mortality from general medical illnesses among persons with bipolar
      disorder: a review.
AB  - OBJECTIVE: Despite recent evidence that patients with bipolar disorder are at
      increased risk of premature mortality resulting from general medical disorders,
      there has been no systematic review of published studies. The authors reviewed
      the literature to determine whether there is evidence of increased risk of
      mortality from general medical causes among patients with bipolar spectrum
      disorders. METHODS: MEDLINE was searched from 1959 to 2007 with a focus on
      bipolar disorder and medical mortality. Published studies in English with more
      than 100 patients were included. RESULTS: Seventeen studies were identified
      involving 331,000 patients with bipolar disorder, affective psychosis, affective
      disorder severe enough to require inpatient psychiatric care or treatment with
      lithium, or schizoaffective disorder (that is, bipolar spectrum disorders)
      meeting the inclusion criteria. Compared with age- and sex-matched control
      samples without mental illness in the general population, mortality ratios for
      death from natural causes and from specific general medical conditions, such as
      cardiovascular, respiratory, cerebrovascular, and endocrine disorders, were
      significantly higher among patients with bipolar spectrum disorders in most
      studies. This finding was more consistent in larger studies with more than 2,500
      patients with bipolar spectrum disorders. Cumulatively, cardiovascular disorder
      appeared to be the most consistent cause of excess mortality in larger studies.
      CONCLUSIONS: The available evidence suggests that bipolar spectrum disorders are
      associated with increased premature mortality secondary to general medical
      illnesses. Unhealthy lifestyle, biological factors, adverse pharmacologic
      effects, and disparities in health care are possible underlying causes for this
      excess mortality.

PMID- 19176411
TI  - The impact of coercion on services from the perspective of mental health care
      consumers with co-occurring disorders.
AB  - OBJECTIVE: Disengagement from services by people with serious mental illnesses
      continues to be a major challenge for the mental health system. Assertive
      community treatment combined with Housing First services is an intervention
      targeted toward consumers whom the system has failed to engage. The processes
      involved in engaging and maintaining consumers in mental health services play an
      important role but remain an understudied aspect of the intervention. This study
      examined the social interaction between consumers and case managers from the
      perspective of consumers. METHODS: Seventy service contacts between unique
      consumer-case manager dyads were sampled. Consumers with co-occurring serious
      mental illness and substance use disorders completed interviews after each
      service contact. They provided information on sociodemographic characteristics,
      service contact characteristics, consumer-provider relationship, utilization of
      coercive strategies, perceived coercion, and service contact evaluation.
      Multivariate regression analyses examined the association of consumer-provider
      relationship and perceived coercion with service contact evaluation. RESULTS:
      Consumer-provider relationship was negatively associated with perceived coercion
      (effect size=.08). Perceived coercion was negatively associated with service
      contact evaluation (effect size=.34). Perceived coercion was positively
      associated with time in the program (effect size=.17) and negatively associated
      with length of the service contact (effect size=.14). Effect sizes ranging from
      .08 to .34 are typically considered small to medium. CONCLUSIONS: Findings
      demonstrate that for consumers, a positive response to service contacts indicated
      that they did not feel coerced. With consumers whose connection to services is
      tenuous, an immediate positive response to service contacts may be vital to
      maintain engagement. Research is needed to identify supportive case manager
      strategies that facilitate relationship building.

PMID- 19176409
TI  - Psychotropic medication nonadherence among United States Latinos: a comprehensive
      literature review.
AB  - OBJECTIVE: Psychotropic medication nonadherence is a major public health problem,
      but few studies have focused on Latinos. The authors systematically reviewed the
      literature on rates of and factors influencing antipsychotic, antidepressant, and
      mood stabilizer nonadherence among U.S. Latinos. METHODS: MEDLINE and PsycINFO
      were searched by using the keywords adherence, compliance, Latino, Hispanic,
      psychotropic, and related terms; bibliographies from relevant reviews and studies
      were also searched. Twenty-one studies met inclusion criteria: published since
      1980 in English or Spanish and measured psychotropic medication nonadherence
      rates among U.S. Latino adults. Information was extracted about study design and
      objective, location, population, medication type, participant demographic
      characteristics, adherence measures, adherence rates, and factors related to
      adherence. RESULTS: In the 17 studies that included Latinos and other minority
      groups, mean nonadherence rates were 41%, 31%, and 43%, respectively, among
      Latinos, Euro-Americans, and African Americans, with an overall effect size of
      .64 between Latinos and Euro-Americans. In the four studies that included only
      Latinos, the mean nonadherence rate was 44%. Ten of 16 studies found that Latinos
      had significantly lower adherence rates than Euro-Americans. Risk factors for
      nonadherence included being a monolingual Spanish speaker, lacking health
      insurance, experiencing access barriers to high-quality care, and having lower
      socioeconomic status. Protective factors included family support and
      psychotherapy. CONCLUSIONS: Rates of nonadherence to psychotropic medications
      were found to be higher for Latinos than for Euro-Americans. Further
      investigation is needed to understand the potentially modifiable individual and
      society-level mechanisms of this discrepancy. Clinical and research interventions
      to improve adherence should be culturally appropriate and incorporate identified
      factors.

PMID- 19176410
TI  - Adherence to antipsychotics among Latinos and Asians with schizophrenia and
      limited English proficiency.
AB  - OBJECTIVES: The authors examined data for 7,784 Latino, Asian, and non-Latino
      white Medi-Cal beneficiaries with schizophrenia to determine the relationship
      between patients' preferred language for mental health services--English,
      Spanish, or an Asian language--and their adherence to treatment with
      antipsychotic medications. METHODS: Data reflected 31,560 person-years from 1999
      to 2004. Pharmacy records were analyzed to assess medication adherence by use of
      the medication possession ratio (MPR). Clients were defined as nonadherent
      (MPR<.5), partially adherent (MPR=.5-<.8), or adherent (MPR=.8-1.1) or as an
      excess filler of prescriptions (MPR<1.1). Regression models were used to examine
      adherence, hospitalization, and costs by race-ethnicity and language status.
      RESULTS: Latinos with limited English proficiency were more likely than English
      proficient Latinos to be medication adherent (41% versus 36%; p<.001) and less
      likely to be excess fillers (15% versus 20%; p<.001). Asians with limited English
      proficiency were less likely than English-proficient Asians to be adherent (40%
      versus 45%; p=.034), more likely to be nonadherent (29% versus 22%; p<.001), and
      less likely to be excess fillers (13% versus 17%; p=.004). When analyses
      controlled for adherence and comorbidities, clients with limited English
      proficiency had lower rates of hospitalization and lower health care costs than
      English-proficient and white clients. CONCLUSIONS: Adherence to antipsychotic
      medications varied by English proficiency among and within ethnic groups.
      Policies supporting the training of bilingual and multicultural providers from
      ethnic minority groups and interventions that capitalize on patients' existing
      social support networks may improve adherence to treatment in linguistically
      diverse populations.

PMID- 19176412
TI  - Assertive community treatment: facilitators and barriers to implementation in
      routine mental health settings.
AB  - OBJECTIVE: This study identified barriers and facilitators to the high-fidelity
      implementation of assertive community treatment. METHODS: As part of a multistate
      implementation project for evidence-based practices, training and consultation
      were provided to 13 newly implemented assertive community treatment teams in two
      states. Model fidelity was assessed at baseline and at six, 12, 18, and 24
      months. Key informant interviews, surveys, and monthly on-site visits were used
      to monitor implementation processes related to barriers and facilitators.
      RESULTS: Licensing processes of the state mental health authority provided
      critical structural supports for implementation. These supports included a
      dedicated Medicaid billing structure, start-up funds, ongoing fidelity
      monitoring, training in the model, and technical assistance. Higher-fidelity
      sites had effective administrative and program leadership, low staff turnover,
      sound personnel practices, and skilled staff, and they allocated sufficient
      resources in terms of staffing, office space, and cars. Lower-fidelity sites were
      associated with insufficient resources, prioritization of fiscal concerns in
      implementation, lack of change culture, poor morale, conflict among staff, and
      high staff turnover. In cross-state comparisons, the specific nature of fiscal
      policies, licensing processes, and technical assistance appeared to influence
      implementation. CONCLUSIONS: State mental health authorities can play a critical
      role in assertive community treatment implementation but should carefully design
      billing mechanisms, promote technical assistance centers, link program
      requirements to fidelity models, and limit bureaucratic requirements. Successful
      implementation at the organizational level requires committed leadership,
      allocation of sufficient resources, and careful hiring procedures.

PMID- 19176413
TI  - Initiation of assertive community treatment among veterans with serious mental
      illness: client and program factors.
AB  - OBJECTIVES: Ensuring equitable access to mental health services is a national
      priority. The authors examined assertive community treatment (ACT) services
      initiation in the Veterans Affairs (VA) health system among program-eligible
      patients. METHODS: The VA's National Psychosis Registry included 6,540 patients
      who met program eligibility criteria (mental illness diagnosis and prior
      hospitalization) in fiscal year (FY) 2003 (FY 2003) and had not received VA ACT
      services in FY 2001-FY 2003. Receipt of VA ACT services during FY 2004 was
      assessed with generalized estimating equations. Independent variables included
      age, gender, race and ethnicity, marital status, service-connected disability
      benefits, substance use disorder, psychiatric inpatient days in FY 2003, distance
      to the nearest facility with a VA ACT team, presence of an on-site team at the
      facility where the last VA psychiatric hospitalization occurred, and number of
      open slots with the nearest ACT team. RESULTS: A total of 452 of the eligible
      patients (7%) received VA ACT services in FY 2004. In multivariate analyses,
      older age was associated with reduced odds of receiving ACT services (odds ratio
      [OR]=.92 per five years); being female (OR=1.86) and having schizophrenia
      (OR=1.64) were positively associated with ACT services initiation. Individuals
      living farther from ACT sites were less likely to receive ACT services (OR=.95
      per ten miles). The marginal effects of distance were most substantial in the
      first 30 miles and beyond 100 miles. CONCLUSIONS: Most patients who were eligible
      for yet not already receiving VA ACT services went without these services in FY
      2004. Geographic distance limited services initiation. Focused efforts are needed
      to enhance ACT services initiation and delivery, particularly for individuals in
      remote locations.

PMID- 19176414
TI  - Implementing the illness management and recovery program in community mental
      health settings: facilitators and barriers.
AB  - OBJECTIVE: There is little research on how to effectively implement the illness
      management and recovery program for people with severe mental illness in
      community mental health settings. This study aimed to examine which factors
      promote or hinder successful implementation of illness management and recovery in
      these settings. METHODS: Twelve community mental health centers implemented
      illness management and recovery over a two-year period. They were supported in
      this endeavor by an implementation resource kit and regular meetings with a
      consultant trainer. Implementation efforts at each center were monitored by a
      supervised researcher (an implementation monitor) over the two years. This
      researcher conducted qualitative interviews with key informants every six months
      and conducted more frequent observations of routine activity in order to discern
      the implementation progress. These qualitative data were gathered into a database
      that was examined by the authors to discern key cross-site barriers to and
      facilitators of the implementation of illness management and recovery. RESULTS:
      Through content analysis of the qualitative data, four broad cross-site themes
      emerged that appear to meaningfully determine success or failure of
      implementation. These were leadership, organizational culture, training, and
      staff and supervision. These overlapping themes worked synergistically to effect
      implementation. CONCLUSIONS: Implementation of illness management and recovery in
      community mental health settings is facilitated through strong leadership, an
      organizational culture that embraces innovation, effective training, and
      committed staff. Where these factors are lacking, strategies may need to be
      developed to effectively implement and sustain illness management and recovery.

PMID- 19176415
TI  - Treatment patterns for schizoaffective disorder and schizophrenia among Medicaid
      patients.
AB  - OBJECTIVE: This study compared background characteristics, pharmacologic
      treatment, and service use of adults treated for schizoaffective disorder and
      adults treated for schizophrenia. METHODS: Medicaid claims data from two states
      were analyzed with a focus on adults treated for schizoaffective disorder or
      schizophrenia. Patient groups were compared regarding demographic
      characteristics, pharmacologic treatment, and health service use during 180 days
      before and after a claim for either schizophrenia or schizoaffective disorder.
      RESULTS: A larger proportion of patients were treated for schizophrenia
      (N=38,760; 70.1%) than for schizoaffective disorder (N=16,570; 29.9%). During the
      180 days before the index diagnosis claim, significantly more patients with
      schizoaffective disorder than those with schizophrenia were treated for
      depressive disorder (19.6% versus 11.4%, p<.001), bipolar disorder (14.8% versus
      5.8%, p<.001), substance use disorder (11.8% versus 9.7%, p<.001), and anxiety
      disorder (6.9% versus 5.3%, p<.001). After the index claim, a similar proportion
      of both diagnostic groups were treated with antipsychotic medications
      (schizoaffective disorder, 87.3%; schizophrenia, 87.0%), although patients with
      schizoaffective disorder were significantly more likely than patients with
      schizophrenia to receive antidepressants (61.7% versus 44.0%, p<.001), mood
      stabilizers (55.2% versus 34.4%, p<.001), and anxiolytics (43.2% versus 35.1%,
      p<.001). Patients with schizoaffective disorder were also significantly more
      likely than patients with schizophrenia to receive psychotherapy (23.4% versus
      13.0%, p<.001) and inpatient mental health care (9.4% versus 6.2%, p<.001),
      although the latter was not significant after the analysis controlled for
      background characteristics. CONCLUSIONS: Schizoaffective disorder is commonly
      diagnosed among Medicaid beneficiaries. These patients often receive complex
      pharmacologic regimens, and many also receive treatment for mood disorders.
      Differences in service use patterns between schizoaffective disorder and
      schizophrenia argue for separate consideration of their health care needs.

PMID- 19176416
TI  - Disparities in use of mental health and substance abuse services by persons with
      co-occurring disorders.
AB  - OBJECTIVES: Individuals with co-occurring mental and substance use disorders
      require psychiatric and substance abuse treatments. A critical question is
      whether these individuals are treated for both disorders. METHODS: This study
      prospectively examined 24-month service utilization patterns of 224 persons with
      co-occurring disorders who were recruited from crisis residential programs in the
      mental health treatment system (N=106) and from crisis residential detoxification
      programs in the substance abuse treatment system (N=118) in San Francisco.
      Utilization data were collected from the billing-information systems of both
      treatment systems. Demographic and clinical data were obtained in interviews with
      participants. Data were analyzed for group differences with chi square tests and
      logistic, linear, and zero-truncated negative binomial regression. RESULTS: After
      the analyses controlled for demographic and clinical factors, participants
      recruited from the substance abuse treatment system were less likely than those
      from the mental health treatment system to obtain any mental health services,
      mental health day treatment, transitional residential care, case management, and
      other outpatient services (p<.001 for all comparisons). They were more likely to
      obtain crisis residential detoxification (p=.003), had more days of drug
      residential treatment (p=.028), but received fewer hours of outpatient services
      (p=.012). CONCLUSIONS: There were disparities in patterns of service utilization,
      although there were no significant diagnostic differences between the two groups.
      These findings should be valuable in considering systems development and
      modification. Furthermore, they can contribute to research about factors that
      underlie results. Study replications should be conducted to assess the robustness
      of these findings in other locales.

PMID- 19176417
TI  - Assessing criminal history as a predictor of future housing success for homeless
      adults with behavioral health disorders.
AB  - OBJECTIVE: Homeless adults with serious mental illnesses and chronic substance
      abuse problems have few housing options, a problem compounded when a criminal
      background is present. This study compared the criminal backgrounds and other
      characteristics of homeless individuals who succeeded in housing (retained
      housing continuously for two years) and those who failed in housing. METHODS: The
      study population consisted of homeless adults with behavioral health disorders
      who moved into supportive housing between January 1, 2000, and June 30, 2004,
      regardless of criminal background. Data about criminal history and other
      characteristics were extracted from existing records and analyzed for
      associations with housing success. Chi square tests and logistic regression
      analysis were used to find characteristics predictive of subsequent housing
      success or failure. RESULTS: Data were available for 347 participants. Most (51%)
      had a criminal record, and 72% achieved housing success. The presence of a
      criminal background did not predict housing failure. Younger age at move-in, the
      presence of a substance abuse problem, and higher numbers of drug crimes and
      property crimes were separately associated with more housing failure; however,
      when they were adjusted for each of the other variables, only move-in age
      remained associated with the outcome. CONCLUSIONS: The finding that criminal
      history does not provide good predictive information about the potential for
      housing success is important because it contradicts the expectations of housing
      operators and policy makers. The findings suggest that policies and practices
      that keep homeless people with criminal records out of housing may be
      unnecessarily restrictive.

PMID- 19176418
TI  - Association between staff factors and levels of conflict and containment on acute
      psychiatric wards in England.
AB  - OBJECTIVE: Conflict (for example, aggression, substance use, and absconding)
      threatens the safety of patients and staff, and containment use (for example,
      coerced medication, special observation, and manual restraint) arouses strong
      feelings and is controversial. Previous work suggests that three staff factors
      have an impact on rates of these events: the positive appreciation of patients by
      staff, the staff's management of their own emotional reactions to patient
      behavior, and the provision of an effective structure. The aim of this study was
      to test this theory. METHODS: A multivariate cross-sectional design was utilized.
      Data were collected for a six-month period on 136 acute psychiatric wards in 26
      National Health Service Trusts in England. Multiple regression was conducted to
      determine the factors most strongly associated with total conflict and
      containment rates. RESULTS: Provision of an effective structure of rules and
      routines for patients was the staff feature most strongly and consistently
      associated with lower conflict and containment rates, with other elements of the
      theory less well supported by the data. Other patient and ward factors were also
      significantly associated with differences in conflict and containment rates
      between wards, in particular the proportion of patients formally detained under
      mental health legislation, the quality of the physical environment, and staff and
      patient race-ethnicity. CONCLUSIONS: Conflict and containment are reliable and
      meaningful concepts. Staff factors are relevant in the determination of conflict
      and containment rates on wards, but the most important of these is the provision
      of an effective, well-organized structure of rules and daily routines. There are
      a number of ways in which conflict on wards might be reduced, including a greater
      emphasis on the production of effective structure and order on the ward and work
      in the community to reduce the numbers of compulsory admissions.

PMID- 19176419
TI  - Using patient-reported outcomes in schizophrenia: the Scottish Schizophrenia
      Outcomes Study.
AB  - OBJECTIVE: The primary aim of the Scottish Schizophrenia Outcomes Study (SSOS)
      was to assess the feasibility and utility of routinely collecting outcome data in
      everyday clinical settings. Data were collected over three years in the Scottish
      National Health Service (NHS). There were two secondary aims of SSOS: first, to
      compare data from patient-rated, objective, and clinician-rated outcomes, and
      second, to describe trends in outcome data and service use across Scotland over
      the three years of the study (2002-2005). METHODS: This study used a
      naturalistic, longitudinal, observational cohort design. A representative sample
      of 1,015 persons with ICD-10 F20-F29 diagnoses (schizophrenia, schizotypal
      disorders, or delusional disorders) was assessed annually using the clinician
      rated measure, the Health of the Nation Outcome Scale (HoNOS), and the patient
      reported assessment, the Avon Mental Health Measure (Avon). Objective outcomes
      data and information on services and interventions were collected. Data were
      analyzed with regression modeling. RESULTS: Of the 1,015 persons recruited, 78%
      of the cohort (N=789) completed the study. Over the study period, significant
      decreases were seen in the number of hospitalizations, incidence of attempted
      suicide and self-harm, and civil detentions. Avon scores indicated significant
      improvement on all subscales (behavior, social, access, and mental health) and on
      the total score. However, HoNOS scores on the behavior and symptom subscales did
      not change, scores on the impairment subscale increased significantly (indicating
      increased levels of impairment), and scores on the social subscale decreased
      significantly (indicating improved social functioning). CONCLUSIONS: This study
      has demonstrated that it is feasible within the Scottish NHS to routinely collect
      meaningful outcomes data in schizophrenia. Patient-reported assessments were also
      successfully collected and used in care plans. This model shows that it is
      possible to incorporate patient-reported assessments into routine care for
      schizophrenia. Such assessments may provide useful data for clinicians and may
      improve treatment adherence. The pattern of outcomes and interventions confirms
      that despite the introduction of guidelines, new treatments, and new services,
      people with schizophrenia continue to have high levels of chronic disability.

PMID- 19176420
TI  - Initial outcomes of a mental illness self-management program based on wellness
      recovery action planning.
AB  - OBJECTIVE: This study examined changes in psychosocial outcomes among
      participants in an eight-week, peer-led, mental illness self-management
      intervention called Wellness Recovery Action Planning (WRAP). METHODS: Eighty
      individuals with serious mental illness at five Ohio sites completed telephone
      interviews at baseline and one month after the intervention. RESULTS: Paired t
      tests of pre- and postintervention scores revealed significant improvement in
      self-reported symptoms, recovery, hopefulness, self-advocacy, and physical
      health; empowerment decreased significantly and no significant changes were
      observed in social support. Those attending six or more sessions showed greater
      improvement than those attending fewer sessions. CONCLUSIONS: These promising
      early results suggest that further research on this intervention is warranted.
      Confirmation of the efficacy and effectiveness of peer-led self-management has
      the potential to enhance self-determination and promote recovery for people with
      psychiatric disabilities.

PMID- 19176421
TI  - Initial evaluation of the Peer-to-Peer program.
AB  - OBJECTIVE: Peer-to-Peer, sponsored by the National Alliance on Mental Illness
      (NAMI), is a structured, experiential, self-empowerment, relapse prevention and
      wellness program led by trained peer mentors for people with mental illnesses.
      The authors conducted the first empirical evaluation of the program by using a
      pre-post survey design. METHODS: Approximately 550 participants who were enrolled
      in Peer-to-Peer during the data collection period (2005-2006) were invited to
      complete a brief, anonymous survey before participating in the program and
      immediately after. RESULTS: Analyses of responses from 138 participants indicated
      that they gained significant benefits, especially in areas central to the Peer-to
      Peer curriculum--specifically, knowledge and management of their illness,
      feelings of being less powerless and more confident, connection with others, and
      completion of an advance directive. Qualitative analysis of responses to an open
      ended postintervention question supported the quantitative findings. CONCLUSIONS:
      Peer-to-Peer is a promising self-help modality that warrants additional
      evaluation with more rigorous methodology.

PMID- 19176422
TI  - A new engagement strategy in a VA-based family psychoeducation program.
AB  - OBJECTIVE: This brief report describes the engagement strategy used in the
      Reaching out to Educate and Assist Caring, Healthy Families (REACH) program, a
      nine-month family psychoeducation program for veterans with serious mental
      illness or posttraumatic stress disorder (PTSD). METHODS: A motivational
      interviewing-based strategy was created and implemented in a Veterans Affairs
      hospital to engage providers and veterans and their families into the
      intervention. RESULTS: Of the 1,539 veterans told about the program, 41% had a
      family member living nearby and were willing to meet with a provider to learn
      more. REACH providers met with 505 veterans for a motivational-interviewing
      session to explore family participation. Of the 436 veterans who were eligible to
      participate in REACH, 28% of veterans with PTSD, 34% of veterans with an
      affective disorder, and 25% of veterans with a schizophrenia spectrum disorder
      went on to participate in at least one session of the REACH program with a family
      member; these rates compare favorably with those for programs requiring a much
      shorter commitment. CONCLUSIONS: This engagement strategy shows promise as an
      effective tool in recruiting veterans and their families into family
      psychoeducation.

PMID- 19176424
TI  - Integrating forensically and civilly committed adult inpatients in a treatment
      mall program at a state hospital.
AB  - OBJECTIVE: This brief report presents outcome data from a 350-bed state
      psychiatric hospital that integrated its adult forensically and civilly committed
      inpatient populations within one rehabilitative program. METHODS: Dorothea Dix
      Hospital, located in Raleigh, North Carolina, used the "treatment mall" model to
      offer all of its resources to all adult patients in a centralized setting.
      Program participation of 100 patients from two long-term civil units was compared
      with program participation of 94 patients from the hospital's medium- and maximum
      security forensic units. RESULTS: The forensic patients were significantly less
      likely to refuse to join or to leave a group, and they were better engaged in
      their treatment. The use of restrictive interventions and the incidence of
      assault were minimal for both groups. CONCLUSIONS: The experience at Dorothea Dix
      Hospital suggests that integrating these populations in rehabilitative
      programming is not only fiscally responsible but also clinically promising, with
      no evidence of greater disruptiveness attributable to forensic patients.

PMID- 19176423
TI  - How quality improvement interventions for depression affect stigma concerns over
      time: a nine-year follow-up study.
AB  - OBJECTIVE: This study examined the long-term impact on stigma concerns of two
      quality improvement (QI) interventions for depression in primary care. METHODS:
      Data were from a nine-year follow-up of 805 participants in Partners in Care, a
      group-level randomized trial comparing patients enrolled in interventions with
      enhanced resources for therapy (QI-therapy) (N=284) or medication management (QI
      meds) (N=267) with those in usual care (N=254). Participants were asked about
      stigma in regard to friends, health insurance, and employers. RESULTS:
      Individuals in QI-therapy were significantly less likely than those in usual care
      and QI-meds to report concerns about friends learning about a history of
      depression (odds ratio [OR]=.66 and .65, respectively), and those in QI-meds were
      more likely than those in QI-therapy and usual care to have concerns about
      getting insurance (OR=1.42 and 1.68, respectively). CONCLUSIONS: Quality
      improvement programs for depression can raise or lower stigma concerns, depending
      on program design and resources for specific treatments.

PMID- 19176425
TI  - An in-home intervention program for children with mental health needs.

PMID- 19176426
TI  - Psychiatric expertise for a multidisciplinary Huntington's disease clinic.

PMID- 19176428
TI  - Disparities in depression care: implications for population-based surveys.

PMID- 19176429
TI  - Increased antipsychotic prescribing to youths in Germany.

PMID- 19176430
TI  - The cover. Boy with a dog.

PMID- 19176431
TI  - FDA panel: ban 2 popular asthma drugs.

PMID- 19176432
TI  - Clinicians advised to step up HIV tests.

PMID- 19176433
TI  - Cardiac CT cancer risks less than feared?

PMID- 19176434
TI  - Reforms needed in adolescent health care.

PMID- 19176435
TI  - Sodium bicarbonate vs sodium chloride in preventing contrast medium-induced
      nephropathy.

PMID- 19176436
TI  - Sodium bicarbonate vs sodium chloride in preventing contrast medium-induced
      nephropathy.

PMID- 19176437
TI  - Sodium bicarbonate vs sodium chloride in preventing contrast medium-induced
      nephropathy.

PMID- 19176438
TI  - Sodium bicarbonate vs sodium chloride in preventing contrast medium-induced
      nephropathy.

PMID- 19176439
TI  - Cytomegalovirus antibody level and mortality among community-dwelling older
      adults with stable cardiovascular disease.

PMID- 19176440
TI  - BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs
      Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME
      CHF) randomized trial.
AB  - CONTEXT: It is uncertain whether intensified heart failure therapy guided by N
      terminal brain natriuretic peptide (BNP) is superior to symptom-guided therapy.
      OBJECTIVE: To compare 18-month outcomes of N-terminal BNP-guided vs symptom
      guided heart failure therapy. DESIGN, SETTING, AND PATIENTS: Randomized
      controlled multicenter Trial of Intensified vs Standard Medical Therapy in
      Elderly Patients With Congestive Heart Failure (TIME-CHF) of 499 patients aged 60
      years or older with systolic heart failure (ejection fraction < or = 45%), New
      York Heart Association (NYHA) class of II or greater, prior hospitalization for
      heart failure within 1 year, and N-terminal BNP level of 2 or more times the
      upper limit of normal. The study had an 18-month follow-up and it was conducted
      at 15 outpatient centers in Switzerland and Germany between January 2003 and June
      2008. INTERVENTION: Uptitration of guideline-based treatments to reduce symptoms
      to NYHA class of II or less (symptom-guided therapy) and BNP level of 2 times or
      less the upper limit of normal and symptoms to NYHA class of II or less (BNP
      guided therapy). MAIN OUTCOME MEASURES: Primary outcomes were 18-month survival
      free of all-cause hospitalizations and quality of life as assessed by structured
      validated questionnaires. RESULTS: Heart failure therapy guided by N-terminal BNP
      and symptom-guided therapy resulted in similar rates of survival free of all
      cause hospitalizations (41% vs 40%, respectively; hazard ratio [HR], 0.91 [95%
      CI, 0.72-1.14]; P = .39). Patients' quality-of-life metrics improved over 18
      months of follow-up but these improvements were similar in both the N-terminal
      BNP-guided and symptom-guided strategies. Compared with the symptom-guided group,
      survival free of hospitalization for heart failure, a secondary end point, was
      higher among those in the N-terminal BNP-guided group (72% vs 62%, respectively;
      HR, 0.68 [95% CI, 0.50-0.92]; P = .01). Heart failure therapy guided by N
      terminal BNP improved outcomes in patients aged 60 to 75 years but not in those
      aged 75 years or older (P < .02 for interaction) CONCLUSION: Heart failure
      therapy guided by N-terminal BNP did not improve overall clinical outcomes or
      quality of life compared with symptom-guided treatment. TRIAL REGISTRATION:
      isrctn.org Identifier: ISRCTN43596477.

PMID- 19176443
TI  - Diagnostic performance of computed tomography angiography in peripheral arterial
      disease: a systematic review and meta-analysis.
AB  - CONTEXT: Computed tomography angiography (CTA) is an increasingly attractive
      imaging modality for assessing lower extremity peripheral arterial disease (PAD).
      OBJECTIVE: To determine the accuracy of CTA compared with intra-arterial digital
      subtraction angiography (DSA) in differentiating extent of disease in patients
      with PAD. DATA SOURCES AND STUDY SELECTION: Search of MEDLINE (January 1966
      August 2008), EMBASE (January 1980-August 2008), and the Database of Abstracts of
      Reviews of Effectiveness for studies comparing CTA with intra-arterial DSA for
      PAD. Eligible studies compared multidetector CTA with intra-arterial DSA,
      included at least 10 patients with intermittent claudication or critical limb
      ischemia, aimed to detect more than 50% stenosis or arterial occlusion, and
      presented either 2 x 2 or 3 x 3 contingency tables (< or = 50% stenosis vs > 50%
      stenosis or occlusion), or provided data allowing their construction. DATA
      EXTRACTION: Two reviewers screened potential studies for inclusion and
      independently extracted study data. Methodological quality was assessed by using
      the QUADAS instrument. DATA SYNTHESIS: Of 909 studies identified, 20 (2.2%) met
      the inclusion criteria. These 20 studies had a median sample size of 33 (range,
      16-279) and included 957 patients, predominantly with intermittent claudication
      (68%). Methodological quality was moderate. Overall, the sensitivity of CTA for
      detecting more than 50% stenosis or occlusion was 95% (95% confidence interval
      [CI], 92%-97%) and specificity was 96% (95% CI, 93%-97%). Computed tomography
      angiography correctly identified occlusions in 94% of segments, the presence of
      more than 50% stenosis in 87% of segments, and absence of significant stenosis in
      96% of segments. Overstaging occurred in 8% of segments and understaging in 15%.
      CONCLUSION: Computed tomography angiography is an accurate modality to assess
      presence and extent of PAD in patients with intermittent claudication; however,
      methodological weaknesses of examined studies prevent definitive conclusions from
      these data.

PMID- 19176444
TI  - Relative child poverty, income inequality, wealth, and health.

PMID- 19176442
TI  - Breast cancer surveillance practices among women previously treated with chest
      radiation for a childhood cancer.
AB  - CONTEXT: Women treated with chest radiation for a pediatric malignancy have a
      significantly increased risk of breast cancer at a young age and are recommended
      to have an annual screening mammogram starting at age 25 years or 8 years after
      radiation, whichever occurs last. OBJECTIVE: To characterize the breast cancer
      surveillance practices among female pediatric cancer survivors who were treated
      with chest radiation and identify correlates of screening. DESIGN, SETTING, AND
      PARTICIPANTS: Between June 2005 and August 2006, a 114-item questionnaire was
      administered to a random sample of 625 women aged 25 through 50 years who had
      survived pediatric cancer, who had been treated with chest radiation, and who
      were participating in the Childhood Cancer Survivor Study (CCSS), a North
      American cohort of long-term survivors diagnosed from 1970-1986. Comparisons were
      made with similarly aged pediatric cancer survivors not treated with chest
      radiation (n = 639) and the CCSS siblings cohort (n = 712). MAIN OUTCOME MEASURE:
      Screening mammogram within the previous 2 years. RESULTS: Of 1976 cancer
      survivors and siblings who were contacted, 87.9% participated. Among the 551
      women with a history of chest radiation, 55% reported a screening mammogram in
      the past 2 years (ages 25-39 years, 36.5%; 95% confidence interval [CI], 31.0%
      42.0%; ages 40-50 years, 76.5%; 95% CI, 71.3%-81.7%). In comparison, 40.5% of
      survivors without chest radiation and 37.0% of CCSS siblings reported a screening
      mammogram in the same time interval. Notably, among women with a history of chest
      radiation, 47.3% (95% CI; 41.6%-53.0%) of those younger than 40 years had never
      had a mammogram and only 52.6% (95% CI; 46.4%-58.8%) of women aged 40 through 50
      years were being regularly screened (2 mammograms within 4 years). Screening
      rates were higher among women who reported a physician recommendation than those
      who did not (ages 25-39 years, 76.0% vs 17.6%; ages 40-50 years, 87.3% vs 58.3%).
      In multivariate models, the association was particularly strong for younger women
      (ages 25-39 years, prevalence ratio [PR], 3.0; 95% CI, 2.0-4.0; ages 40-50 years,
      PR, 1.3; 95% CI, 1.1-1.6). CONCLUSIONS: In this cohort of women who had childhood
      cancer treated with chest radiation, 63.5% of those aged 25 through 39 years and
      23.5% of those aged 40 through 50 years had not had mammography screening for
      breast cancer within the previous 2 years despite a guideline recommendation that
      survivors of childhood cancer who were treated with chest radiation should
      undergo annual screening mammography.

PMID- 19176441
TI  - Genome-wide interrogation of germline genetic variation associated with treatment
      response in childhood acute lymphoblastic leukemia.
AB  - CONTEXT: Pediatric acute lymphoblastic leukemia (ALL) is the prototype for a drug
      responsive malignancy. Although cure rates exceed 80%, considerable unexplained
      interindividual variability exists in treatment response. OBJECTIVES: To assess
      the contribution of inherited genetic variation to therapy response and to
      identify germline single-nucleotide polymorphisms (SNPs) associated with risk of
      minimal residual disease (MRD) after remission induction chemotherapy. DESIGN,
      SETTING, AND PATIENTS: Genome-wide interrogation of 476,796 germline SNPs to
      identify genotypes that were associated with MRD in 2 independent cohorts of
      children with newly diagnosed ALL: 318 patients in St Jude Total Therapy
      protocols XIIIB and XV and 169 patients in Children's Oncology Group trial P9906.
      Patients were enrolled between 1994 and 2006 and last follow-up was in 2006. MAIN
      OUTCOME MEASURES: Minimal residual disease at the end of induction therapy,
      measured by flow cytometry. RESULTS: There were 102 SNPs associated with MRD in
      both cohorts (median odds ratio, 2.18; P < or = .0125), including 5 SNPs in the
      interleukin 15 (IL15) gene. Of these 102 SNPs, 21 were also associated with
      hematologic relapse (P < .05). Of 102 SNPs, 21 were also associated with
      antileukemic drug disposition, generally linking MRD eradication with greater
      drug exposure. In total, 63 of 102 SNPs were associated with early response,
      relapse, or drug disposition. CONCLUSION: Host genetic variations are associated
      with treatment response for childhood ALL, with polymorphisms related to leukemia
      cell biology and host drug disposition associated with lower risk of residual
      disease.

PMID- 19176445
TI  - Describing physician language fluency: deconstructing medical Spanish.

PMID- 19176446
TI  - Why guideline-making requires reform.

PMID- 19176447
TI  - BNP-guided therapy for heart failure.

PMID- 19176449
TI  - JAMA patient page. Acute lymphoblastic leukemia.

PMID- 19176448
TI  - Surveillance for breast cancer after childhood cancer.

PMID- 19176450
TI  - Beyond the Gail model: lobular involution may help refine breast cancer risk
      assessment.

PMID- 19176452
TI  - Re: False-positive results in cancer epidemiology: a plea for epistemological
      modesty.

PMID- 19176451
TI  - Human papillomavirus type 18 DNA load and 2-year cumulative diagnoses of cervical
      intraepithelial neoplasia grades 2-3.
AB  - BACKGROUND: The clinical relevance of the amount of human papillomavirus type 18
      (HPV18) DNA in cervical tissue (ie, HPV18 DNA load) is unknown. METHODS: Study
      subjects were 303 women who were HPV18 positive at enrollment into the Atypical
      Squamous Cells of Undetermined Significance (ASC-US) and Low-Grade Squamous
      Intraepithelial Lesion (LSIL) Triage Study. HPV18 DNA load, expressed as copies
      of HPV18 per nanogram of cellular DNA, at enrollment was quantitatively measured.
      Subjects were followed up semiannually for a period of 2 years for detection of
      cervical intraepithelial neoplasia 2-3 (CIN2-3). A linear regression model was
      used to examine associations of CIN2-3 with HPV18 DNA load. All statistical tests
      were two-sided. RESULTS: CIN2-3 was confirmed in 92 of 303 (30.4%) HPV18-positive
      women. Among women without CIN2-3, HPV18 DNA load was positively associated with
      increasing severity of cervical cytology at enrollment (Ptrend < .001). However,
      among those with CIN2-3, HPV18 DNA load was not associated with severity of
      cervical cytology at enrollment (Ptrend = .33). The ratios of geometric means of
      HPV18 DNA load at enrollment among women with CIN2-3, relative to those without,
      were 6.06 (95% confidence interval [CI] = 0.31 to 117.92) for those with normal
      cytology at enrollment, 0.50 (95% CI = 0.10 to 2.44) for those with ASC-US, 0.11
      (95% CI = 0.03 to 0.46) for those with LSIL, and 0.07 (95% CI = 0.01 to 0.80) for
      those with high-grade squamous intraepithelial lesion (HSIL). After adjusting for
      age and coinfection with other high-risk HPVs, a statistically significant
      association of lower HPV18 DNA load with CIN2-3 was observed among women with
      LSIL or HSIL at enrollment (P = .02). Within the 2-year period, HPV18 DNA load
      was unrelated to the timing of CIN2-3 diagnosis. Overall results were similar
      when the outcome was CIN3. CONCLUSIONS: HPV18 DNA load was higher for women with
      LSIL or HSIL at enrollment with no evidence of CIN2-3 during the 2-year follow-up
      period than it was for women with CIN2-3. Thus, testing for high levels of HPV18
      DNA does not appear to be clinically useful.

PMID- 19176453
TI  - Agents targeting apoptosis show promise in early trials.

PMID- 19176455
TI  - Prognostic value of measuring load of human papillomavirus DNA in cervical
      samples: an elusive target.

PMID- 19176454
TI  - Phase 3 randomized trial on larynx preservation comparing sequential vs
      alternating chemotherapy and radiotherapy.
AB  - BACKGROUND: Both induction chemotherapy followed by irradiation and concurrent
      chemotherapy and radiotherapy have been reported as valuable alternatives to
      total laryngectomy in patients with advanced larynx or hypopharynx cancer. We
      report results of the randomized phase 3 trial 24954 from the European
      Organization for Research and Treatment of Cancer. METHODS: Patients with
      resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or
      hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and
      with no metastasis, were randomly assigned to treatment in the sequential (or
      control) or the alternating (or experimental) arm. In the sequential arm,
      patients with a 50% or more reduction in primary tumor size after two cycles of
      cisplatin and 5-fluorouracil received another two cycles, followed by
      radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of
      cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with
      radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy
      cycles (60 Gy total). All nonresponders underwent salvage surgery and
      postoperative radiotherapy. The Kaplan-Meier method was used to obtain time-to
      event data. RESULTS: The 450 patients were randomly assigned to treatment (224 to
      the sequential arm and 226 to the alternating arm). Median follow-up was 6.5
      years. Survival with a functional larynx was similar in sequential and
      alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence
      interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years,
      respectively) and median progression-free interval (3.0 and 3.1 years,
      respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in
      the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients
      in the alternating arm. Late severe edema and/or fibrosis was observed in 32
      (16%) patients in the sequential arm and in 25 (11%) in the alternating arm.
      CONCLUSIONS: Larynx preservation, progression-free interval, and overall survival
      were similar in both arms, as were acute and late toxic effects.

PMID- 19176456
TI  - T670X KIT mutations in gastrointestinal stromal tumors: making sense of missense.
AB  - BACKGROUND: Chronic myeloid leukemia, gastrointestinal stromal tumors (GISTs),
      and idiopathic hypereosinophilic syndrome are associated with pathological
      deregulation of the tyrosine kinases BCR-ABL, KIT, and PDGFRA, respectively.
      Patients who become resistant to imatinib treatment often develop secondary
      mutations, the most common of which results in a substitution of isoleucine for
      threonine at the same location in the ATP-binding domain in all three kinases (in
      KIT this occurs at amino acid 670). We sought to determine why Thr is always
      replaced by Ile. METHODS: All possible point mutations in the DNA triplet codon
      that could result in amino acid substitutions at Thr670 (Thr670Arg, Thr670Ile,
      Thr670Lys, Thr670Ala, Thr670Ser, Thr670Pro) were introduced by site-specific
      mutagenesis of the complementary DNA for a constitutively active, imatinib
      sensitive form of the KIT receptor, Delta559/KIT. The resulting mutant KIT
      proteins were transiently expressed in COS1 African green monkey kidney cells
      grown with and without imatinib, and cell extracts were analyzed for KIT
      activation by immunoprecipitation and immunoblotting to determine
      autophosphorylation levels. We also performed molecular modeling to estimate the
      relative affinities of wild-type (Thr670) KIT and the KIT mutants for ATP and
      imatinib. RESULTS: Like the parental strain, Thr670Ala, Thr670Ser, and Thr670Lys
      mutants were inhibited by 5 microM imatinib, but in comparison, they were only
      weakly active and Thr670Pro and Thr670Arg were not active at all. Only the
      Thr670Ile mutant was fully active (autophosphorylated) and resistant to imatinib.
      These findings were consistent with computer modeling predictions that ranked
      these mutants Thr - Ile > Ala, Ser > Lys >> Pro according to their affinity for
      ATP but Thr > Ala, Ser > Lys >Pro - Arg - Ile according to their affinity for
      imatinib. CONCLUSIONS: This combination of in vitro and molecular modeling
      analyses shows why, among all possible amino acid substitutions at position 670
      of KIT, only Ile is naturally selected as a resistance mutant in imatinib-treated
      GIST patients.

PMID- 19176458
TI  - Estimated risk of radiation-induced breast cancer from mammographic screening for
      young BRCA mutation carriers.
AB  - BRCA mutation carriers are recommended to start mammographic screening for breast
      cancer as early as age 25-30 years. We used an excess relative risk model (based
      on a pooled analysis of three cohorts with 7600 subjects who received radiation
      exposure) to estimate the lifetime risk of radiation-induced breast cancer from
      five annual mammographic screenings in young (<40 years) BRCA mutation carriers.
      We then estimated the reduction in breast cancer mortality required to outweigh
      the radiation risk. Breast cancer rates for mutation carriers were based on a
      pooled analysis of 22 pedigree studies with 8139 subjects. For BRCA1 mutation
      carriers, the estimated lifetime risk of radiation-induced breast cancer
      mortality per 10,000 women resulting from annual mammography was 26 (95%
      confidence interval [CI] = 14 to 49) for screening at age 25-29 years, 20 (95% CI
      = 11 to 39) for screening at age 30-34 years, and 13 (95% CI = 7 to 23) for
      screening at age 35-39 years. To outweigh these risks, screening would have to
      reduce breast cancer mortality by 51% (95% CI = 27% to 96%) at age 25-29 years,
      by 12% (95% CI = 6% to 23%) at age 30-34 years, and by 4% (95% CI = 2% to 7%) at
      age 35-39 years; estimates were similar for BRCA2 mutation carriers. If we assume
      that the mortality reduction from mammography is 15%-25% or less for young women,
      these results suggest that there would be no net benefit from annual mammographic
      screening of BRCA mutation carriers at age 25-29 years; the net benefit would be
      zero or small at age 30-34 years, but there should be some net benefit at age 35
      or older. These results depend on a number of assumptions due to the absence of
      empiric data. The impact of varying these assumptions was therefore examined.

PMID- 19176457
TI  - A germline mutation (A339V) in thyroid transcription factor-1 (TITF-1/NKX2.1) in
      patients with multinodular goiter and papillary thyroid carcinoma.
AB  - BACKGROUND: The genetic factors that determine the risk of papillary thyroid
      carcinoma (PTC) among patients with multinodular goiter (MNG) remain undefined.
      Because thyroid transcription factor-1 (TTF-1) is important to thyroid
      development, we evaluated whether the gene that encodes it, TITF-1/NKX2.1, is a
      genetic determinant of MNG/PTC predisposition. METHODS: Twenty unrelated PTC
      patients with a history of MNG (MNG/PTC), 284 PTC patients without a history of
      MNG (PTC), and 349 healthy control subjects were screened for germline
      mutation(s) in TITF-1/NKX2.1 by sequencing of amplified DNA from blood. The
      effects of the mutation on the growth and differentiation of thyroid cells were
      demonstrated by ectopic expression of wild-type (WT) and mutant proteins in PCCL3
      normal rat thyroid cells, followed by tests of cell proliferation, activation of
      cell growth pathways, and transcription of TTF-1 target genes. All statistical
      tests were two-sided. RESULTS: A missense mutation (1016C>T) was identified in
      TITF-1/NKX2.1 that led to a mutant TTF-1 protein (A339V) in four of the 20
      MNG/PTC patients (20%). These patients developed substantially more advanced
      tumors than MNG/PTC or PTC patients without the mutation (P = .022, Fisher exact
      test). Notably, this germline mutation was dominantly inherited in two families,
      with some members bearing the mutation affected with MNG, associated with either
      PTC or colon cancer. The mutation encoding the A339V substitution was not found
      among the 349 healthy control subjects nor among the 284 PTC patients who had no
      history of MNG. Overexpression of A339V TTF-1 in PCCL3 cells, as compared with
      overexpression of WT TTF-1, was associated with increased cell proliferation
      including thyrotropin-independent growth (average A339V proliferation rate =
      134.27%, WT rate = 104.43%, difference = 34.3%, 95% confidence interval = 12.0%
      to 47.7%, P = .010), enhanced STAT3 activation, and impaired transcription of the
      thyroid-specific genes Tg, TSH-R, and Pax-8. CONCLUSION: This is the first
      germline mutation identified in MNG/PTC patients. It could contribute to
      predisposition for MNG and/or PTC and to the pathogenesis of PTC.

PMID- 19176459
TI  - StatBite: WHO funding and the burden of disease in the Western Pacific region.

PMID- 19176460
TI  - Searching for less toxic larynx preservation: a need for common definitions and
      metrics.

PMID- 19176461
TI  - Melanoma vaccines: possible progress after years of frustration?

PMID- 19176462
TI  - Re: Nonmelanoma skin cancer and risk for subsequent malignancy.

PMID- 19176465
TI  - Re: False-positive results in cancer epidemiology: a plea for epistemological
      modesty.

PMID- 19176464
TI  - Trial offers early test case for personalized medicine.

PMID- 19176463
TI  - The role of STAT-3 in the induction of apoptosis in pancreatic cancer cells by
      benzyl isothiocyanate.
AB  - BACKGROUND: Benzyl isothiocyanate (BITC), a compound found in cruciferous
      vegetables, has been reported to have anticancer properties, but the mechanism
      whereby it inhibits growth of human pancreatic cancer cells is incompletely
      understood. METHODS: Human pancreatic cancer cells (BxPC-3, AsPC-1, Capan-2,
      MiaPaCa-2, and Panc-1) and immortalized human pancreatic cells (HPDE-6) were
      treated with vehicle or with BITC at 5-40 microM, cell survival was evaluated by
      sulforhodamine B assay, and apoptosis by caspase-3 and poly-ADP ribose polymerase
      cleavage or by a commercial assay for cell death. Total and activated signal
      transducer and activator of transcription-3 (STAT-3) protein expression in the
      cells were examined by western blotting, STAT-3 mRNA levels by reverse
      transcription-polymerase chain reaction, and STAT-3 DNA-binding and
      transcriptional activity by commercially available binding and reporter assays.
      The effects of BITC treatment on tumor growth, apoptosis, and STAT-3 protein
      expression in vivo were studied in xenografts of BxPC-3 pancreatic tumor cells in
      athymic nude mice. All statistical tests were two-sided. RESULTS: BITC treatment
      reduced cell survival and induced apoptosis in BxPC-3, AsPC-1, Capan-2, and
      MiaPaCa-2 cells, and to a much lesser extent in Panc-1 cells, but not in HPDE-6
      cells. It also reduced levels of activated and total STAT-3 protein, and as a
      result, STAT-3 DNA-binding and transcriptional activities. Overexpression of STAT
      3 in BxPC-3 cells inhibited BITC-induced apoptosis and restored STAT-3 activity.
      In mice that were fed BITC (60 micromol/wk, five mice, 10 tumors per group),
      growth of BxPC-3 pancreatic tumor xenografts was suppressed compared with control
      mice (at 6 weeks, mean tumor volume of control vs BITC-treated mice = 334 vs 172
      mm3, difference =162 mm3, 95% confidence interval = 118 to 204 mm3; P = .008) and
      tumors had increased apoptosis and reduced STAT-3 protein expression. CONCLUSION:
      BITC induces apoptosis in some types of pancreatic cancer cells by inhibiting the
      STAT-3 signaling pathway.

PMID- 19176466
TI  - Thyrotropin and homologous glycoprotein hormone receptors: structural and
      functional aspects of extracellular signaling mechanisms.
AB  - The TSH receptor (TSHR) together with the homologous lutropin/choriogonadotropin
      receptor and the follitropin receptor are glycoprotein hormone receptors (GPHRs).
      They constitute a subfamily of the rhodopsin-like G protein-coupled receptors
      with seven transmembrane helices. GPHRs and their corresponding hormones are
      pivotal proteins with respect to a variety of physiological functions. The
      identification and characterization of intra- and intermolecular signaling
      determinants as well as signaling mechanisms are prerequisites to gaining
      molecular insights into functions and (pathogenic) dysfunctions of GPHRs.
      Knowledge about activation mechanisms is fragmentary, and the specific aspects
      have still not been understood in their entirety. Therefore, here we critically
      review the data available for these receptors and bring together structural and
      functional findings with a focus on the important large extracellular portion of
      the TSHR. One main focus is the particular function of structural determinants in
      the initial steps of the activation such as: 1) hormone binding at the
      extracellular site; 2) hormone interaction at a second binding site in the hinge
      region; 3) signal regulation via sequence motifs in the hinge region; and 4)
      synergistic signal amplification by cooperative effects of the extracellular
      loops toward the transmembrane region. Comparison and consolidation of data from
      the homologous glycoprotein hormone receptors TSHR, follitropin receptor, and
      lutropin/choriogonadotropin receptor provide an overview of extracellular
      mechanisms of signal initiation, conduction, and regulation at the TSHR and
      homologous receptors. Finally, we address the issue of structural implications
      and suggest a refined scenario for the initial signaling process on GPHRs.

PMID- 19176468
TI  - Technical assistance as a prevention capacity-building tool: a demonstration
      using the getting to outcomes framework.
AB  - Demands on community-based prevention programs for performance accountability and
      positive outcomes are ever increasing in the face of constrained resources.
      Relatively little is known about how technical assistance (TA) should be
      structured to benefit community-based organizations and to lead to better
      outcomes. In this study, data from multiple sources were used to describe an
      effective TA model designed to improve the capacity of community-based
      organizations to plan, implement, and evaluate prevention programming. This
      article is the first of its kind to provide detailed analyses of the TA delivered
      to community-based organizations to build substance abuse prevention capacity.
      The results of this study describe the range of TA services provided and the
      importance of two-way communication between the TA provider and recipient. TA
      recipients reported high satisfaction and an improved understanding of targeted
      TA activities. However, achieving these benefits requires significant program
      staff time, and not all skills were successfully transferred. Results from this
      study suggest how TA may be structured to be effective in supporting quality
      prevention programming in community settings.

PMID- 19176467
TI  - Androgen receptor roles in spermatogenesis and fertility: lessons from testicular
      cell-specific androgen receptor knockout mice.
AB  - Androgens are critical steroid hormones that determine the expression of the male
      phenotype, including the outward development of secondary sex characteristics as
      well as the initiation and maintenance of spermatogenesis. Their actions are
      mediated by the androgen receptor (AR), a member of the nuclear receptor
      superfamily. AR functions as a ligand-dependent transcription factor, regulating
      expression of an array of androgen-responsive genes. Androgen and the AR play
      important roles in male spermatogenesis and fertility. The recent generation and
      characterization of male total and conditional AR knockout mice from different
      laboratories demonstrated the necessity of AR signaling for both external and
      internal male phenotype development. As expected, the male total AR knockout mice
      exhibited female-typical external appearance (including a vagina with a blind end
      and a clitoris-like phallus), the testis was located abdominally, and germ cell
      development was severely disrupted, which was similar to a human complete
      androgen insensitivity syndrome or testicular feminization mouse. However, the
      process of spermatogenesis is highly dependent on autocrine and paracrine
      communication among testicular cell types, and the disruption of AR throughout an
      experimental animal cannot answer the question about how AR in each type of
      testicular cell can play roles in the process of spermatogenesis. In this review,
      we provide new insights by comparing the results of cell-specific AR knockout in
      germ cells, peritubular myoid cells, Leydig cells, and Sertoli cells mouse models
      that were generated by different laboratories to see the consequent defects in
      spermatogenesis due to AR loss in different testicular cell types in
      spermatogenesis. Briefly, this review summarizes these results as follows: 1) the
      impact of lacking AR in Sertoli cells mainly affects Sertoli cell functions to
      support and nurture germ cells, leading to spermatogenesis arrest at the
      diplotene primary spermatocyte stage prior to the accomplishment of first meiotic
      division; 2) the impact of lacking AR in Leydig cells mainly affects
      steroidogenic functions leading to arrest of spermatogenesis at the round
      spermatid stage; 3) the impact of lacking AR in the smooth muscle cells and
      peritubular myoid cells in mice results in similar fertility despite decreased
      sperm output as compared to wild-type controls; and 4) the deletion of AR gene in
      mouse germ cells does not affect spermatogenesis and male fertility. This review
      tries to clarify the useful information regarding how androgen/AR functions in
      individual cells of the testis. The future studies of detailed molecular
      mechanisms in these in vivo animals with cell-specific AR knockout could possibly
      lead to useful insights for improvements in the treatment of male infertility,
      hypogonadism, and testicular dysgenesis syndrome, and in attempts to create safe
      as well as effective male contraceptive methods.

PMID- 19176469
TI  - Clustering of schizophrenia with other comorbidities--what can we learn?

PMID- 19176471
TI  - Influence of emotional expression on memory recognition bias in schizophrenia as
      revealed by fMRI.
AB  - We recently showed that, in healthy individuals, emotional expression influences
      memory for faces both in terms of accuracy and, critically, in memory response
      bias (tendency to classify stimuli as previously seen or not, regardless of
      whether this was the case). Although schizophrenia has been shown to be
      associated with deficit in episodic memory and emotional processing, the relation
      between these processes in this population remains unclear. Here, we used our
      previously validated paradigm to directly investigate the modulation of emotion
      on memory recognition. Twenty patients with schizophrenia and matched healthy
      controls completed functional magnetic resonance imaging (fMRI) study of
      recognition memory of happy, sad, and neutral faces. Brain activity associated
      with the response bias was obtained by correlating this measure with the contrast
      subjective old (ie, hits and false alarms) minus subjective new (misses and
      correct rejections) for sad and happy expressions. Although patients exhibited an
      overall lower memory performance than controls, they showed the same effects of
      emotion on memory, both in terms of accuracy and bias. For sad faces, the similar
      behavioral pattern between groups was mirrored by a largely overlapping neural
      network, mostly involved in familiarity-based judgments (eg, parahippocampal
      gyrus). In contrast, controls activated a much larger set of regions for happy
      faces, including areas thought to underlie recollection-based memory retrieval
      (eg, superior frontal gyrus and hippocampus) and in novelty detection (eg,
      amygdala). This study demonstrates that, despite an overall lower memory
      accuracy, emotional memory is intact in schizophrenia, although emotion-specific
      differences in brain activation exist, possibly reflecting different strategies.

PMID- 19176472
TI  - Seeking verisimilitude in a class: a systematic review of evidence that the
      criterial clinical symptoms of schizophrenia are taxonic.
AB  - This review examines whether there is evidence that the criterion symptoms of
      Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV)
      schizophrenia are taxonic--that schizophrenia is not part of a single
      distribution of normality. Two taxometric methods, coherent cut kinetics (CCK)
      and latent variable modeling (LVM), are demonstrated to be sensitive to latent
      classes and, therefore, were regarded as providing relevant statistical evidence.
      A systematic literature search identified 24 articles describing analyses of 28
      participant cohorts in which CCK or LVM methods were used with one or more
      criterion symptoms of schizophrenia. Virtually all analyses yielded results that,
      on first impression, favored taxonic over dimensional interpretations of the
      latent structure of schizophrenia. However, threats to the internal and external
      validity of these studies--including biased or inadequate analyses, violation of
      statistical assumptions, inadequate indicator screening, and the introduction of
      systematic error through recruitment and sampling--critically undermine this body
      of work. Uncertainties about the potential effects of perceptual biases, unimodal
      assessment, and item parceling are also identified, as are limitations in seeking
      to validate classes with single or double dissociations of outcomes. We conclude
      that there is no reason to seriously doubt a single-distribution model of
      schizophrenia because there is no evidence that provides a serious test of this
      null hypothesis. A second fundamental question remains outstanding: is
      schizophrenia truly a group of schizophrenias, with taxonic divisions separating
      its types? We make design and analysis suggestions for future research addressing
      these questions.

PMID- 19176470
TI  - Psychosocial treatments to promote functional recovery in schizophrenia.
AB  - A number of psychosocial treatments are available for persons with schizophrenia
      that include social skills training, cognitive behavioral therapy, cognitive
      remediation, and social cognition training. These treatments are reviewed and
      discussed in terms of how they address key components of functional recovery such
      as symptom stability, independent living, work functioning, and social
      functioning. We also review findings on the interaction between pharmacological
      and psychosocial treatments and discuss future directions in pharmacological
      treatment of schizophrenia. Overall, these treatments provide a range of
      promising approaches to helping patients achieve better outcomes far beyond
      symptom stabilization.

PMID- 19176473
TI  - Psychological causes of schizophrenia.
AB  - This article outlines not only the path of my recovery but also the conclusions
      of my therapeutic journal that developed over a period of several years. This
      journal evolved into the following structure: description of personal pain body,
      moving forward with transformations, and active living--implementation of
      intention and desire that continues. My journal has evolved from the written word
      to transformation, current lived experience, and the expectation of good things
      yet to come. Many transformations were integrated into my thinking and emotions
      over the years. As I developed solutions to my pain body, the structure of the
      psychological causes of my paranoid schizophrenia became clear. The voices and
      interference are at bay, hallucinations and delusions are understood, and
      paranoid disposition transformed to a more normal way of thinking and reacting. I
      continue on a low maintenance dose of atypical antipsychotic medication. My hope
      is that my conclusions will inspire researchers and clinicians and help other
      peers with their recovery. An open mind, moving forward in work, self-direction,
      and transformative learning have contributed significantly to my recovery.

PMID- 19176474
TI  - Delusions are associated with poor cognitive insight in schizophrenia.
AB  - The purpose of the study was to investigate the relationship between the symptoms
      delusions and hallucinations measured by the Positive and Negative Syndrome Scale
      and cognitive insight as assessed with the Beck Cognitive Insight Scale (BCIS) in
      patients with schizophrenia. The BCIS is based on 2 subscales, self
      reflectiveness and self-certainty, measuring objectivity, reflectiveness and
      openness to feedback, and mental flexibility. Overall cognitive insight was
      defined as the difference between self-reflectiveness and self-certainty. This
      cross-sectional study of 143 patients showed that the occurrence of delusions is
      associated with low self-reflectiveness and high self-certainty, reflecting low
      cognitive insight. Hallucinations in the absence of delusions were associated
      with high self-reflectiveness and low self-certainty, possibly reflecting more
      open-mindedness and higher cognitive insight. The present findings suggest that
      delusions are associated with low cognitive insight, whereas solitary
      hallucinations may be associated with high cognitive insight.

PMID- 19176475
TI  - Limits on Medicare's ability to control rising spending on cancer drugs.

PMID- 19176476
TI  - Identification of proteomic differences between squamous cell carcinoma of the
      lung and bronchial epithelium.
AB  - Proteins that exhibit different expression levels in normal and malignant lung
      cells are good candidate biomarkers to improve early diagnosis and intervention.
      We used a quantitative approach and compared the proteome of microdissected cells
      from normal human bronchial epithelium and squamous cell carcinoma tumors of
      histopathological grades G2 and G3. DIGE analysis and subsequent MS-based protein
      identification revealed that 32 non-redundant proteins were differentially
      regulated between the respective tissue types. These proteins are mainly involved
      in energy pathways, cell growth or maintenance mechanisms, protein metabolism,
      and the regulation of DNA and RNA metabolism. The expression of some of these
      proteins was analyzed by immunohistochemistry using tissue microarrays containing
      tissue specimen of 55 patients, including normal bronchial epithelium, squamous
      cell carcinomas, adenocarcinomas, and large cell carcinomas. The results of the
      immunohistochemical studies correlated with the proteome study data and revealed
      that particularly HSP47 and a group of cytokeratins (i.e. cytokeratins 6a, 16,
      and 17) are significantly co-regulated in squamous cell carcinoma. Furthermore
      cytokeratin 17 showed significantly higher abundance in G2 grade compared with G3
      grade squamous cell carcinomas in both the gel-based and the immunohistochemical
      analysis. Therefore this protein might be used as a marker for stratification
      between different tumor grades.

PMID- 19176477
TI  - G Protein Mono-ubiquitination by the Rsp5 Ubiquitin Ligase.
AB  - Emerging evidence suggests that ubiquitination serves as a protein trafficking
      signal in addition to its well characterized role in promoting protein
      degradation. The yeast G protein alpha subunit Gpa1 represents a rare example of
      a protein that undergoes both mono- and poly-ubiquitination. Whereas mono
      ubiquitinated Gpa1 is targeted to the vacuole, poly-ubiquitinated Gpa1 is
      directed instead to the proteasome. Here we investigate the structural
      requirements for mono- and poly-ubiquitination of Gpa1. We find that variants of
      Gpa1 engineered to be unstable are more likely to be poly-ubiquitinated and less
      likely to be mono-ubiquitinated. In addition, mutants that cannot be
      myristoylated are no longer mono-ubiquitinated but are still polyubiquitinated.
      Finally, we show that the ubiquitin ligase Rsp5 is necessary for Gpa1 mono
      ubiquitination in vivo and that the purified enzyme is sufficient to catalyze
      Gpa1 mono-ubiquitination in vitro. Taken together, these data indicate that mono-
      and poly-ubiquitination have distinct enzyme and substrate recognition
      requirements; whereas poly-ubiquitination targets misfolded protein for
      degradation, a distinct ubiquitination apparatus targets the fully mature, fully
      myristoylated G protein for mono-ubiquitination and delivery to the vacuole.

PMID- 19176478
TI  - Ilicicolin Inhibition and Binding at Center N of the Dimeric Cytochrome bc1
      Complex Reveal Electron Transfer and Regulatory Interactions between Monomers.
AB  - We have determined the kinetics of ilicicolin binding and dissociation at center
      N of the yeast bc(1) complex and its effect on the reduction of cytochrome b with
      center P blocked. The addition of ilicicolin to the oxidized complex resulted in
      a non-linear inhibition of the extent of cytochrome b reduction by quinol
      together with a shift of the reduced b(H) heme spectrum, indicating electron
      transfer between monomers. The possibility of a fast exchange of ilicicolin
      between center N sites was excluded in two ways. First, kinetic modeling showed
      that fast movement of an inhibitor between monomers would result in a linear
      inhibition of the extent of cytochrome b reduction through center N. Second, we
      determined a very slow dissociation rate for ilicicolin (k = 1.2 x 10(-3) s(-1))
      as calculated from its displacement by antimycin. Ilicicolin binding to the
      reduced bc(1) complex occurred in a single phase (k(on) = 1.5-1.7 x 10(5) m(-1)
      s(-1)) except in the presence of stigmatellin, where a second slower binding
      phase comprising approximately 50% of the spectral change was observed. This
      second kinetic event was weakly dependent on ilicicolin concentration, which
      suggests that binding of ilicicolin to one center N in the dimer transmits a slow
      (k = 2-3 s(-1)) conformational change that allows binding of the inhibitor in the
      other monomer. These results, together with the evidence for intermonomeric
      electron transfer, provide further support for a dimeric model of regulatory
      interactions between center P and center N sites in the bc(1) complex.

PMID- 19176479
TI  - Crystal structure of malaria parasite nucleosome assembly protein: distinct modes
      of protein localization and histone recognition.
AB  - Nucleosome assembly proteins (NAPs) are histone chaperones that are essential for
      the transfer and incorporation of histones into nucleosomes. NAPs participate in
      assembly and disassembly of nucleosomes and in chromatin structure organization.
      Human malaria parasite Plasmodium falciparum contains two nucleosome assembly
      proteins termed PfNapL and PfNapS. To gain structural insights into the mechanism
      of NAPs, we have determined and analyzed the crystal structure of PfNapL at 2.3 A
      resolution. PfNapL, an ortholog of eukaryotic NAPs, is dimeric in nature and
      adopts a characteristic fold seen previously for yeast NAP-1 and Vps75 and for
      human SET/TAF-1b (beta)/INHAT. The PfNapL monomer is comprised of domain I,
      containing a dimerization alpha-helix, and a domain II, composed of alpha-helices
      and a beta-subdomain. Structural comparisons reveal that the "accessory domain,"
      which is inserted between the domain I and domain II in yeast NAP-1 and other
      eukaryotic NAPs, is surprisingly absent in PfNapL. Expression of green
      fluorescent protein-tagged PfNapL confirmed its exclusive localization to the
      parasite cytoplasm. Attempts to disrupt the PfNapL gene were not successful,
      indicating its essential role for the malaria parasite. A detailed analysis of
      PfNapL structure suggests unique histone binding properties. The crucial
      structural differences observed between parasite and yeast NAPs shed light on
      possible new modes of histone recognition by nucleosome assembly proteins.

PMID- 19176480
TI  - Lipid raft segregation modulates TRPM8 channel activity.
AB  - Transient receptor potential channels are a family of cation channels involved in
      diverse cellular functions. Most of these channels are expressed in the nervous
      system and play a key role in sensory physiology. TRPM8 (transient receptor
      potential melastatine 8), a member of this family, is activated by cold, cooling
      substances such menthol and icilin and voltage. Although TRPM8 is a
      thermosensitive channel highly expressed in cold sensory neurons, the mechanisms
      underlying its temperature sensitivity are still poorly understood. Here we show
      that, in sensory neurons, TRPM8 channel is localized in cholesterol-rich
      specialized membrane domains known as lipid rafts. We also show that, in
      heterologous expression systems, lipid raft segregation of TRPM8 is favored by
      glycosylation at the Asn(934) residue of the polypeptide. In electrophysiological
      and imaging experiments, using cold and menthol as agonists, we also demonstrate
      that lipid raft association modulates TRPM8 channel activity. We found that
      menthol- and cold-mediated responses of TRPM8 are potentiated when the lipid raft
      association of the channel is prevented. In addition, lipid raft disruption
      shifts the threshold for TRPM8 activation to a warmer temperature. In view of
      these data, we suggest a role for lipid rafts in the activity and temperature
      sensitivity of TRPM8. We propose a model wherein different lipid membrane
      environments affect the cold sensing properties of TRPM8, modulating the response
      of cold thermoreceptors.

PMID- 19176481
TI  - Heparan sulfate-modulated, metalloprotease-mediated sonic hedgehog release from
      producing cells.
AB  - The ectodomains of numerous proteins are released from cells by matrix
      metalloproteases to yield soluble intercellular regulators. A disintegrin and
      metalloprotease (ADAM) family members have often been found to be the responsible
      "sheddases," ADAM17/tumor necrosis factor-alpha-converting enzyme being its best
      characterized member. In this work, we show that ShhNp (lipidated and membrane
      tethered Sonic hedgehog) is released from Bosc23 cells by metalloprotease
      mediated ectodomain shedding, resulting in a soluble and biologically active
      morphogen. ShhNp shedding is increased by ADAM17 coexpression and cholesterol
      depletion of cells with methyl-beta-cyclodextrin and is reduced by
      metalloprotease inhibitors as well as ADAM17 RNA interference. We also show that
      the amount of shed ShhNp is modulated by extracellular heparan sulfate (HS) and
      that ShhNp shedding depends on specific HS sulfations. Based on those data, we
      suggest new roles for metalloproteases, including but not restricted to ADAM17,
      and for HS-proteoglycans in Hedgehog signaling.

PMID- 19176482
TI  - Presenilin 1 affects focal adhesion site formation and cell force generation via
      c-Src transcriptional and posttranslational regulation.
AB  - Presenilin 1 and 2 (PS) are critical components of the gamma-secretase complex
      that cleaves type I transmembrane proteins within their transmembrane domains.
      This process leads to release of proteolytically processed products from cellular
      membranes and plays an essential role in signal transduction or vital functions
      as cell adhesion. Here we studied the function of presenilins in cell-matrix
      interaction of wild-type and PS knock-out mouse embryonic fibroblasts. We found
      for PS1(-/-) cells an altered morphology with significantly reduced sizes of
      focal adhesion sites compared with wild type. Cell force analyses on
      micropatterned elastomer films revealed PS1(-/-) cell forces to be reduced by
      50%. Pharmacological inhibition confirmed this function of gamma-secretase in
      adhesion site and cell force formation. On the regulatory level, PS1 deficiency
      was associated with strongly decreased phosphotyrosine levels of focal adhesion
      site-specific proteins. The reduced tyrosine phosphorylation was caused by a down
      regulation of c-Src kinase activity primarily at the level of c-Src
      transcription. The direct regulatory connection between PS1 and c-Src could be
      identified with ephrinB2 as PS1 target protein. Overexpression of ephrinB2
      cytoplasmic domain resulted in its nuclear translocation with increased levels of
      c-Src and a full complementation of the PS1(-/-) adhesion and phosphorylation
      phenotype. Cleavage of full-length EB2 and subsequent intracellular domain
      translocation depended on PS1 as these processes were only found in WT cells.
      Therefore, we conclude that gamma-secretase is vital for controlling cell
      adhesion and force formation by transcriptional regulation of c-Src via ephrinB2
      cleavage.

PMID- 19176483
TI  - Women's retirement expectations: how stable are they?
AB  - OBJECTIVE: Using the National Longitudinal Survey of Mature Women, we examine
      between- and within-person differences in expected retirement age as a key
      element of the retirement planning process. The expectation typologies of 1,626
      women born between 1923 and 1937 were classified jointly on the basis of
      specificity and consistency. METHODS: Latent class analysis was used to determine
      retirement expectation patterns over a 7-year span. Multinomial logistic
      regression analyses were employed to estimate the effects of demographic and
      status characteristics on the likelihood of reporting 4 distinct longitudinal
      patterns of retirement expectations. RESULTS: Substantial heterogeneity in
      reports of expected retirement age between and within individuals over the 7-year
      span was found. Demographic and status characteristics, specifically age, race,
      marital status, job tenure, and recent job change, sorted respondents into
      different retirement expectation patterns. CONCLUSIONS: The frequent within
      person fluctuations and substantial between-person heterogeneity in retirement
      expectations indicate uncertainty and variability in both expectations and
      process of expectation formation. Variability in respondents' reports suggests
      that studying retirement expectations at multiple time points better captures the
      dynamics of preretirement planning.

PMID- 19176484
TI  - Remembered parenting styles and adjustment in middle and late adulthood.
AB  - BACKGROUND: Authoritative parenting is the parenting style often associated with
      positive outcomes for children and adolescents. This study considers whether
      remembered parenting styles in childhood predict multiple dimensions of
      functioning in adulthood. METHODS: We used the 1995 National Survey of Midlife
      Development in the United States data set (N = 2,232) to assess the association
      between parenting behaviors remembered from childhood-classified as
      authoritative, authoritarian, indulgent, and uninvolved-and psychological well
      being, depressive symptoms, and substance abuse, in a subsample of mid- and later
      life adults. Differences in outcomes by sex, race, and childhood socioeconomic
      status were also examined across parenting styles. RESULTS: Adults who remembered
      authoritative compared with authoritarian and uninvolved parents reported greater
      psychological well-being and fewer depressive symptoms, and those with uninvolved
      parents noted greater substance abuse. No outcome differences were found between
      remembered authoritative and indulgent parenting styles. A few sex and race
      interactions were identified: Authoritative parenting (compared with uninvolved)
      was more strongly associated with men's psychological well-being than women's,
      and authoritative parenting (compared with authoritarian) predicted reduced
      depressive symptoms for Whites more than non-Whites. CONCLUSIONS: There is some
      support that remembered parenting styles continue to be related to functioning
      across the lifespan. There is also evidence of resiliency, flexibility, and
      malleability in human development.

PMID- 19176485
TI  - Racial differences in self-rated health at similar levels of physical
      functioning: an examination of health pessimism in the health, aging, and body
      composition study.
AB  - BACKGROUND: The health pessimism hypothesis suggests that Black elders are more
      pessimistic about health than Whites and therefore tend to report lower self
      rated health (SRH) at comparable health status. The current analysis examined the
      factors associated with SRH and tested the health pessimism hypothesis among
      older adults at similar levels of physical functioning. METHODS: The study
      example included 2,729 Health, Aging, and Body Composition study participants
      aged 70-79 years. We used hierarchical logistic regression to examine the
      association between race and SRH while adjusting for demographic, physical
      health, and psychosocial factors. The analyses were repeated for participants at
      similar levels of objective functioning to test the health pessimism hypothesis.
      RESULTS: The association between race and SRH remained independent of physical
      and psychosocial health variables, with Whites being 3.7 times more likely than
      Black elders to report favorable SRH. This association was significant at each
      level of physical functioning and greater at the higher (odds ratio [OR] = 5.5)
      versus lower (OR = 2.2) levels of functioning. CONCLUSIONS: The results suggest
      greater health pessimism among Black elders and expand previous work by including
      objective functioning in multidimensional models to deconstruct race variations
      in the SRH of older adults.

PMID- 19176486
TI  - Gender differences in spousal caregiving in Japan.
AB  - BACKGROUND: Gender differences in spousal caregivers and their relationship to
      care experiences, social demographics, and caregivers' depression were examined.
      METHODS: A stratified random sample of 2,020 users of public long-term care
      insurance in a city of Osaka prefecture, Japan, participated in this study.
      Responses from 308 spouses (56.2% wives, 43.8% husbands) were analyzed. Variables
      relating to care experiences, social demographics, and caregivers' depression
      were compared by conducting simultaneous analyses of multiple populations.
      RESULTS: Wives caring for husbands had higher depression scores than husbands
      caring for wives. Wives tended to adopt "emotional support seeking" and "willing
      commitment" as coping strategies for their caregiving experience. Husband
      caregivers used more home-care services; however, increased service use had no
      effect on husbands' depression. The availability of secondary caregivers reduced
      depression for caregivers, regardless of gender. CONCLUSIONS: The effects on
      depression differed related to the caregiver's gender. Husbands relied more on
      family or home-care services when caring for their wives, whereas wives provided
      higher levels of care, positively accepted their role, and did not seek to share
      caregiving, but sought emotional support.

PMID- 19176487
TI  - Living alone and depressive symptoms: the influence of gender, physical
      disability, and social support among Hispanic and non-Hispanic older adults.
AB  - BACKGROUND: Is living alone a risk factor for depression among older adults?
      Previous research is mixed and inconclusive, and it is unclear whether living
      alone influences psychological distress independently of other interrelated risk
      factors for depression. We reexamine this association and evaluate whether it is
      contingent on gender, physical disability, social support, and Hispanic
      ethnicity. METHODS: We analyze data from a multiethnic sample of older disabled
      and nondisabled adults residing in Miami-Dade County, Florida (n = 947). We
      employ descriptive and multivariate analyses stratified by Hispanic ethnicity to
      assess the relationship between living alone and depressive symptoms and evaluate
      whether any association is conditioned by gender, physical disability, and social
      support. RESULTS: Living alone is associated with higher levels of depressive
      symptoms among Hispanics but not among non-Hispanics. Variations in social
      support did not account for the higher overall levels of depression reported by
      Hispanics living alone relative to their counterparts living with a spouse,
      partner, or others. However, social support moderated the association between
      living alone and depression among both Hispanics and non-Hispanics. CONCLUSIONS:
      We discuss the implications of our findings for future research, especially as
      they relate to observed ethnic differences in the relationship between living
      alone and depressive symptoms.

PMID- 19176489
TI  - Molecular characterization of feline COX-2 and expression in feline mammary
      carcinomas.
AB  - Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the biosynthesis of
      prostaglandins, plays an important role in inflammation and tumorigenesis. COX-2
      primary structure has been characterized in many species and its expression
      demonstrated in a variety of cancers in humans and dogs, including mammary
      cancer. In contrast, there is currently little information on the structure of
      feline COX-2. Also, information on COX-2 expression in feline mammary cancer is
      limited and conflicting. The objectives of this study were therefore to
      characterize the molecular structure of feline COX-2 and to evaluate by
      immunohistochemistry its expression in mammary carcinomas. Our results show that
      the predicted coding region of feline COX-2 encodes a 604-amino acid protein,
      which is identical in length to several COX-2 homologs. Feline COX-2 amino acid
      sequence is highly similar to other mammalian COX-2 homologs. Immunohistochemical
      analysis of 40 mammary carcinomas showed that the majority of tumors studied
      (35/40; 87%) expressed COX-2 at a level varying from low (20/40; 50%) to
      intermediate (13/40; 32%) and high (2/40; 5%). These results provide the first
      molecular characterization of feline COX-2 and demonstrate that COX-2 is
      expressed in the majority of feline mammary carcinomas.

PMID- 19176488
TI  - Within-family variability in representations of past relationships with parents.
AB  - BACKGROUND: We examined within-family variation in siblings' memories of
      experiences with parents and their associations with current positive and
      negative affect. METHODS: Participants were 1,369 adults with at least 1 sibling,
      aged 26-74 years from 498 families in the MacArthur Study of Midlife in the
      United States (M(age) = 47 years, 59% women, 94% White). RESULTS: There was
      considerable variability in recalled maternal and paternal treatment across the
      dimensions of affection (intraclass correlation coefficients [ICCs] 0.33 and
      0.41, respectively), discipline (ICCs 0.39 and 0.43), and conflict (ICCs 0.24 and
      0.26). In turn, recalled parental treatment, particularly affection, made unique
      contributions to current positive (ICC 0.12) and negative affect (ICC 0.08) over
      and above individual and familial level characteristics such as offspring
      demographic characteristics, extraversion and neuroticism, family structure,
      recalled early family environment, and parents' current status. CONCLUSIONS:
      Results link adults' memories of experiences with their parents in childhood to
      their current well-being and highlight the importance of considering within
      family models for family theory.

PMID- 19176490
TI  - Pathologic analysis of the brain from Streptococcus suis type 2 experimentally
      infected pigs.
AB  - Streptococcus suis type 2 (S. suis 2) is known as a major porcine pathogen
      worldwide and causes meningitis, septicemia, endocarditis, arthritis, and septic
      shock in pigs. Suilysin, a secreted protein of S. suis 2, is considered to be an
      important S. suis 2 virulence-associated factor. In this paper, the cerebellar
      lesions following experimental infection of pigs with S. suis 2 were studied. An
      immunohistochemical technique was applied to compare the distribution of bacteria
      and secreted suilysin protein in brain. The infected pigs developed histologic
      lesions of meningoencephalitis. Immunohistochemistry identified bacteria within
      the cytoplasm of neutrophils and macrophages localized in meningeal lesions. The
      secreted suilysin protein showed a similar localization within the cytoplasm of
      inflammatory cells, indicating that suilysin had high expression in vivo and may
      contribute to the pathogenesis of streptococcal meningoencephalitis.

PMID- 19176491
TI  - Increased expression of BRCA2 and RAD51 in lymph node metastases of canine
      mammary adenocarcinomas.
AB  - The BRCA/RAD51 complex of tumor suppressor genes plays a major role in the DNA
      damage response. In this explorative study, BRCA1, BRCA2, and RAD51 mRNA
      expression was quantified in highly defined laser microdissected tissue samples
      of simple adenomas, adenocarcinomas of the mammary gland, and their lymph node
      metastases by real-time quantitative reverse transcription polymerase chain
      reaction. Expression levels in the tumors were normalized to the geometric mean
      of 3 housekeeping genes and quantified relative to normal mammary epithelium of
      the same dog. In adenomas, mRNA expression was reduced for BRCA1 (6/10 dogs,
      60%), BRCA2 (4/10 dogs, 40%), and RAD51 (4/10, 40%). In adenocarcinomas BRCA1
      expression varied with increased expression in 3 of 10 (30%) dogs and no
      differences in 7 of 10 (70%) dogs when compared with normal mammary gland. BRCA2
      and RAD51 were overexpressed in 5 of 10 (50%) and 6 of 10 (60%) of
      adenocarcinomas, respectively. An overexpression of RAD51 and BRCA2 was found in
      8 of 10 (80%) and 5 of 10 (50%) of the lymph node metastases, respectively.
      Direct comparison of primary tumors and metastases revealed increased mRNA
      expression of BRCA1 (2/10 dogs, 20%), BRCA2 (2/10 dogs, 20%), and RAD51 (3/10
      dogs, 30%) in lymph node metastases. Taken together, the results suggest that
      RAD51 is upregulated in the majority of lymph node metastases of canine mammary
      tumors. Further experimental studies are needed to clarify whether these changes
      in gene expression are a direct carcinogenetic stimulus or a protective response
      due to genetic instability during tumor progression.

PMID- 19176492
TI  - Identification of cancer stem cells in dog glioblastoma.
AB  - There is increasing evidence in some malignancies that the tumor clone is
      heterogeneous in regard to proliferation and differentiation. The cancer stem
      cell hypothesis implies that not all the cells in the tumor have the same
      capacity to proliferate and maintain the growth of the tumor. Only a relatively
      small fraction of cells in the tumor, termed cancer stem cells (CSCs), possess
      the ability to proliferate and self-renew extensively. In the past decade,
      several groups have reported the existence of a CSC population in different human
      brain tumors from both children and adults. We report here the identification of
      a CSC population from a Boxer dog with glioblastoma multiforme (GBM) that
      possesses a great capacity for proliferation, self-renewal, and differentiation.
      This cloned cell line is aneuploid, forms neurospheres in culture, possesses CSC
      markers, and reproduces the original dog GBM when inoculated into the nude mouse
      brain.

PMID- 19176493
TI  - Hydronephrosis and urine retention in estrogen-implanted athymic nude mice.
AB  - Subcutaneous estrogen pellet implantation is commonly practiced to induce tumor
      promotion in nude (Nu-FOXn1(nu)) mice for xenograft tumor modeling. Twelve of 23,
      18-week-old nude mice developed dysuria after estrogen pellet implantation.
      Physical examination revealed variably distended abdomens with palpable distended
      bladders. All mice were euthanatized and postmortem examinations were made. Blood
      samples of the mice were collected, and serum estrogen concentration was
      measured. Postmortem examination revealed variable dilation of the urinary
      bladder and unilateral or bilateral dilations of ureters and kidneys.
      Microscopically, 12 of 23 mice and 13 of 23 mice showed dilated urinary bladder
      and hydronephrosis, respectively.

PMID- 19176494
TI  - Review paper: the role of inflammation in mouse pulmonary neoplasia.
AB  - Inflammation is a risk factor for the development of many types of neoplasia,
      including skin, colon, gastric, and mammary cancers, among others. Chronic
      pulmonary diseases, such as chronic bronchitis and asthma, predispose to lung
      neoplasia. We will review the mouse literature examining the role of inflammation
      in lung neoplasia, focusing specifically on genetic susceptibility, pharmacologic
      modulation of inflammatory pathways, and both transgenic and knockout mouse
      models used to assess pro- and anti-inflammatory pathways involved in lung
      neoplasia. Identification of molecular mechanisms that govern the association
      between inflammation and pulmonary neoplasia could provide novel preventive,
      diagnostic, and therapeutic strategies for a disease in which few biomarkers
      currently exist.

PMID- 19176495
TI  - Massive visceral pentastomiasis caused by Porocephalus crotali in a dog.
AB  - The testes of a 5-year-old, male, crossbred Schnauzer dog were the indicator
      organs for detection of massive pentastomiasis. Necropsy revealed numerous
      additional encysted parasites within the mesenteric lymph nodes, omentum, liver,
      sub-serosa of the small and large intestines, mesentery, and lungs. The nymphs
      had a pseudosegmented body, containing large eosinophilic glands and a chitinous
      cuticle with characteristic pores. Their hook configuration was consistent with
      that of Porocephalus. A pentastomid-specific 18S rRNA polymerase chain reaction
      (PCR) was designed and used to amplify template for sequencing. The sequence of
      the PCR product was 99.7% homologous with the reference sequence for P. crotali.
      This pentastomid parasite has been reported in North American snakes of genera
      Crotalus and Agkistrodon. Mammals are intermediate hosts, and snakes are the
      definitive hosts. Porocephalus crotali has been reported in dogs only once, and
      molecular methods have not been used previously to identify the species in
      clinical pentastomiasis.

PMID- 19176496
TI  - Ectonucleoside triphosphate diphosphohydrolase type 5 (Entpd5)-deficient mice
      develop progressive hepatopathy, hepatocellular tumors, and spermatogenic arrest.
AB  - Ectonucleoside triphosphate diphosphohydrolase type 5 (ENTPD5, also CD39L4) is a
      soluble enzyme that hydrolyzes purine nucleoside diphosphates. Genetic
      inactivation of ENTPD5 in mice (Entpd5(-/-)) resulted in 2 major histopathologic
      lesions: hepatopathy and aspermia. The hepatopathy was progressive and
      characterized by centrilobular hepatocyte hypertrophy, oval cell proliferation,
      bile staining of Kupffer cells, and hepatocyte degeneration with increasing
      incidence and severity of degenerative lesions, development of multiple foci of
      cellular alteration, and hepatocellular neoplasia with age. Greatly increased
      proliferation of hepatocytes in young adult as well as aged Entpd5(-/-) mice was
      demonstrated by Ki67 immunohistochemistry and 5'-bromo-3'-deoxyuridine
      incorporation. Of 15 Entpd5(-/-) mice between 44 and 69 weeks of age, all showed
      foci of cellular alteration in the liver, and at least 6 of 15 developed
      hepatocellular carcinoma (HCC), hepatocellular adenoma, or both. Significantly,
      none of these lesions were observed in 13 wild-type Entpd5(+/+) littermates.
      These findings, combined with the historically low incidence (about 5%) of HCC in
      mice up to 2 years of age with the same genetic background, strongly suggest that
      loss of Entpd5 promotes hepatocellular neoplasia in mice. In humans, ENTPD5 has
      been found to be identical to the PCPH proto-oncogene, and dysregulation of this
      gene has been demonstrated in some human cancers. This mouse model could
      contribute to the understanding of the influence of ENTPD5/PCPH on cellular
      proliferation and neoplasia.

PMID- 19176497
TI  - Expression of androgen receptor in mammary glands in ovariectomized cynomolgus
      monkeys.
AB  - This study investigated structural alterations and the immunohistochemical
      expression of androgen receptor (AR), estrogen receptor (ER), and progesterone
      receptor (PgR) in the mammary glands from surgically postmenopausal cynomolgus
      monkeys (Macaca fascicularis). Fourteen animals were divided into 2 groups. Seven
      animals underwent an ovariectomy (OVX), and the other 7 animals underwent a sham
      operation (sham). The in-life phase of study was 78 weeks. Atrophy in the mammary
      glands of OVX monkeys was similar to early postmenopausal atrophy of the human
      breast. The proportion of AR-positive cells in the OVX group was significantly
      higher than in the sham group, but the proportion of ER and PgR-positive cells
      was significantly lower. These results suggest that use of a primate model for
      hormone receptor expression has potential applications in basic human
      endocrinology, particularly in research in hormone receptor expression in mammary
      glands (both normal and neoplastic).

PMID- 19176498
TI  - Gas bubbles in seals, dolphins, and porpoises entangled and drowned at depth in
      gillnets.
AB  - Gas bubbles were found in 15 of 23 gillnet-drowned bycaught harp (Pagophilus
      groenlandicus), harbor (Phoca vitulina) and gray (Halichoerus grypus) seals,
      common (Delphinus delphis) and white-sided (Lagenorhyncus acutus) dolphins, and
      harbor porpoises (Phocaena phocaena) but in only 1 of 41 stranded marine mammals.
      Cases with minimal scavenging and bloating were chilled as practical and
      necropsied within 24 to 72 hours of collection. Bubbles were commonly visible
      grossly and histologically in bycaught cases. Affected tissues included lung,
      liver, heart, brain, skeletal muscle, gonad, lymph nodes, blood, intestine,
      pancreas, spleen, and eye. Computed tomography performed on 4 animals also
      identified gas bubbles in various tissues. Mean +/- SD net lead line depths (m)
      were 92 +/- 44 and ascent rates (ms(-1)) 0.3 +/- 0.2 for affected animals and 76
      +/- 33 and 0.2 +/- 0.1, respectively, for unaffected animals. The relatively good
      carcass condition of these cases, comparable to 2 stranded cases that showed no
      gas formation on computed tomography (even after 3 days of refrigeration in one
      case), along with the histologic absence of bacteria and autolytic changes,
      indicate that peri- or postmortem phase change of supersaturated blood and
      tissues is most likely. Studies have suggested that under some circumstances,
      diving mammals are routinely supersaturated and that these mammals presumably
      manage gas exchange and decompression anatomically and behaviorally. This study
      provides a unique illustration of such supersaturated tissues. We suggest that
      greater attention be paid to the radiology and pathology of bycatch mortality as
      a possible model to better understand gas bubble disease in marine mammals.

PMID- 19176499
TI  - Pleomorphic corneal sarcoma resembling malignant peripheral nerve sheath tumor in
      a horse.
AB  - A 14-year-old Haflinger gelding presented with a protruding mass involving the
      cornea of the right eye. The mass was resected and submitted for histopathologic
      and immunohistochemical examination. The preliminary diagnosis was corneal
      sarcoma, most likely fibrosarcoma. The immunohistochemical results confirmed the
      mesenchymal origin of the neoplastic cells, which were most consistent with a
      malignant peripheral nerve sheath tumor. Corneal mesenchymal neoplasms are
      extremely uncommon tumors in human beings and domestic animals. The cause for
      this tumor was not determined; infection with bovine papillomavirus was not
      detected.

PMID- 19176500
TI  - Vasoformative disorder, resembling littoral cell angioma, of the spleen in a
      geriatric Japanese macaque (Macaca fuscata).
AB  - A 30-year-old female Japanese macaque showed marked splenomegaly. The enlarged
      spleen consisted of neoplastic proliferation of anastomosing vascular channels
      resembling morphologic structures of red pulp sinuses; occasionally, papillary
      fronds were seen in dilated channels. Immunohistochemically, the lining cells
      reacted to both endothelial cell (von Willebrand factor) and macrophage
      (macrophage scavenger receptor class A) markers, indicating features of littoral
      cells of the spleen. Based on the pathologic characteristics, particularly the
      presence of neoplastic cells with macrophage/histiocyte-like attributes, this
      tumor was regarded as littoral cell angioma; this is a rare benign splenic
      vascular tumor.

PMID- 19176501
TI  - Canine duplication of Descemet's membrane.
AB  - The morphology of a duplication phenomenon of the canine Descemet's membrane (DM)
      is described in relation to signalment, history, and ocular disease status. Sixty
      six canine eyes from the Comparative Ocular Pathology Laboratory of Wisconsin
      archives between 2000 and 2007 were examined. All cases were stained with
      hematoxylin and eosin and Alcian blue periodic acid-Schiff (PAS), while 14 cases
      were additionally stained with Masson's trichrome, picrosirius red, cytokeratin
      AE1/AE3 (CK), vimentin, and alpha-smooth muscle actin (SMA). Transmission
      electron microscopy (TEM) examination was performed in 3 corneas and in 1 normal
      control eye. Alcian blue PAS staining and TEM confirmed the basement membrane
      nature of the abnormal secondary DM. The thickness of the first DM, referred to
      as the corneal layer (CL) and the second or anterior chamber layer (ACL), were
      nearly the same, with no significant difference seen (P = .93). In 39% (26/66) of
      the eyes, a fibrous, collagenous matrix component was present between the CL and
      ACL, which contains vimentin-positive and alpha-SMA-negative spindle cells
      (14/14).The corneal endothelial cells in 7/14 eyes stained weakly with CK and
      strongly in 2 additional eyes. The most frequent histopathologically confirmed,
      clinical ocular histories were chronic glaucoma in 76% (50/66) of eyes, previous
      intraocular surgery in 36% (24/66), lens luxation in 21% (4/66), and blunt trauma
      in 15% (10/66) of the cases. We speculate that activation and migration of
      endothelial cells, in association with trauma or lens contact, play a role in the
      pathogenesis of this phenomenon.

PMID- 19176502
TI  - Idiopathic chondrolysis condition in two young, wild-caught Cynomolgus monkeys
      (Macaca fascicularis) reared in captivity.
AB  - Idiopathic chondrolysis is a human clinical entity typically reported in
      adolescent individuals. In this brief communication, we report 2 cases of
      presumptive idiopathic chondrolysis of the femoral head in Cynomolgus macaques
      and discuss the clinical symptomatology and pathology of the disease. In detail,
      we describe the histomorphologic changes of idiopathic chondrolysis and compare
      these findings with those typically observed in the primary differential
      diagnoses of Legg-Calve-Perthes disease and nonspecific osteoarthritis.
      Consideration of this entity among differential diagnoses in young Cynomolgus
      macaques with unilateral osteoarthritis could be important both for laboratory
      animal veterinarians and pathologists.

PMID- 19176503
TI  - Epithelioid cells in mediastinal lymph nodes of cattle without cancer.
AB  - Epithelioid cells are found in lymph nodes in cases of metastatic carcinoma;
      however, epithelioid cells with benign features have also been discovered
      incidentally in lymph nodes. Epithelioid cells were observed in mediastinal lymph
      nodes of cattle without cancer during routine diagnostic necropsy. To explain
      this finding, the authors evaluated the prevalence and histopathologic,
      immunohistochemical, and ultrastructural features retrospectively using
      mediastinal lymph nodes from 110 cattle and found that 66 of the lymph nodes
      contained epithelioid cells. In all 66 nodes, most of the epithelioid cells were
      individual or aggregated in nodal sinuses; in 21 nodes, some epithelioid cells
      formed tubular structures. The individual and aggregated epithelioid cells were
      mostly considered to be mesothelial in origin by immunohistochemical and
      ultrastructural examination; presumably, they entered the lymph nodes via
      lymphatic vessels, because they were found in afferent lymphatic vessels and
      nodal sinuses. Although the presence of epithelioid cells in lymph nodes prompts
      suspicion of metastatic carcinoma, the epithelioid cells in these bovine lymph
      nodes did not disrupt nodal architecture, lacked atypia or mitotic figures, and
      did not invade nodal parenchyma.

PMID- 19176504
TI  - Disseminated chlorellosis in a dog.
AB  - An adult dog with ataxia and a lingual mass, previously diagnosed as
      protothecosis, was euthanized. At the postmortem examination, the lingual mass,
      regions of the lungs and hilar lymph nodes, liver, mesenteric and sublumbar lymph
      nodes, and spinal meninges had pronounced green discoloration. Histologically,
      pyogranulomatous inflammation and algal organisms were found in the tongue,
      spinal meninges, hilar and mesenteric lymph nodes, liver, and lung. The algae had
      cell walls positive for periodic acid-Schiff and cytoplasmic granules.
      Ultrastructurally, the algae had a well-defined cell wall, stacks of grana and
      thylakoid membrane, and dense bodies, typical of starch granules. The organisms
      were identified as Chlorella, a green alga, based on the results of
      histochemistical and electron microscopic examination. To the author's knowledge
      this is the first report of disseminated Chlorella infection and the first report
      in a companion animal.

PMID- 19176505
TI  - Bilateral ovarian malignant mixed Mullerian tumor in a dog.
AB  - Malignant mixed Mullerian tumor (MMMT) is a rare neoplasm of the female genital
      tract. We report a case of bilateral ovarian MMMT in a 10-year-old female dog.
      Ovaries were only moderately enlarged with a papillary surface and firm nodules.
      Multiple metastases were observed in the abdominal cavity and pulmonary
      parenchyma. Histologically, both ovaries had intermingled carcinomatous and
      sarcomatous components with cartilage and bone. Metastatic lesions were not
      mixed. The peritoneal metastases were carcinomatous; pulmonary metastases were
      sarcomatous. Carcinomatous elements of the MMMT were immunohistochemically
      positive for cytokeratin (CK) AE1/AE3, CK7, and vimentin and estrogen receptors.
      Conversely, the sarcomatous cells were positive for vimentin, but negative for
      CKs. Chondrocytes also expressed S-100 protein. On the basis of similarities to
      human ovarian MMMT, the diagnosis was heterologous malignant mixed Mullerian
      tumor of the ovary.

PMID- 19176506
TI  - Immunohistochemical features of dystrophic axons in Papillon dogs with
      neuroaxonal dystrophy.
AB  - The immunohistochemical features of dystrophic axons in brain tissues of Papillon
      dogs with neuroaxonal dystrophy (NAD) were examined in comparison with 1 dog with
      cerebellar cortical abiotrophy (CCA) and a dog without neurologic signs.
      Histologically, many dystrophic axons were observed throughout the central
      nervous system of all dogs with NAD. These axonal changes were absent in the dog
      with CCA and in the control dog. Severe Purkinje cell loss was found in the dog
      with CCA, whereas the lesions were milder in all dogs with NAD.
      Immunohistochemically, the many dystrophic axons were positive for
      neurofilaments, tau, alpha/beta-synuclein, HSP70, ubiquitin, synaptophysin,
      syntaxin-1, and synaptosomal-associated protein-25 (SNAP-25). A few dystrophic
      axons were positive for alpha-synuclein. In addition, these dystrophic axons,
      especially in the nucleus gracilis, cuneatus, olivaris, and spinal tract of the
      trigeminal nerve, were intensely immunopositive for the 3 calcium-binding
      proteins calretinin, calbindin, and parvalbumin. The accumulation of synapse
      associated proteins in the dystrophic axons may indicate dysfunction of the
      synapse at the presynaptic portion. The accumulation of alpha-synuclein in the
      dystrophic axon and region-specific appearance of calcium-binding protein
      positive spheroids are considered as unique features in NAD of Papillon dogs,
      providing the key to elucidate the pathogenesis.

PMID- 19176507
TI  - Pulmonary myxoma in a sheep.
AB  - Pulmonary myxoma is an uncommon neoplasm. A pale tan, lobulated, and well
      circumscribed mass was discovered at slaughter in the left lung of a 5-year-old
      sheep. Histologically, the tumor was composed of spindloid to stellate cells in a
      myxoid matrix. Neoplastic cells were immunohistochemically positive for vimentin
      but did not express cytokeratins, S-100 protein, smooth muscle actin, desmin, or
      p53. On the basis of the histologic and immunohistochemical findings, this tumor
      was diagnosed as a myxoma.

PMID- 19176508
TI  - Diagnostic exercise: epithelioid hemangiosarcoma mimicking metastatic prostatic
      neoplasia in a dog.
AB  - A 10-year-old intact male Labrador Retriever dog was euthanized because of rapid
      deterioration after suffering from mild chronic cough, hematuria, acute
      blindness, ataxia, and lethargy. Clinical examination revealed blepharospasm and
      hyphema, with clear discharge from the right eye; a firm mass in an enlarged
      right testicle; a mass in the irregularly enlarged prostate; and nodules in the
      left kidney, liver, and spleen detected by abdominal sonography. Cytologic
      evaluation of fine needle aspirates from the prostate, testis, and kidney
      comprised large, clustered or individualized, anaplastic cells that lacked
      convincing tissue differentiation. Necropsy examination revealed an irregularly
      enlarged prostate with dark tan to red zones and multiple, discrete, beige to
      dark red nodules that ranged from 0.5 to 6 cm in diameter in the lung, liver,
      left kidney, right testis, colon wall, stomach wall, and brain. On histologic
      examination, discrete nests of anaplastic carcinoma-like tumor cells were found
      in sections of all affected organs. Results of immunohistochemical examination
      revealed widespread expression of von Willebrand factor and the absence of
      cytokeratin in neoplastic cells. The diagnosis was metastatic epithelioid
      hemangiosarcoma, primary site unknown.

PMID- 19176509
TI  - Thymic cystic degeneration, pseudoepitheliomatous hyperplasia, and hemorrhage in
      a dog with brodifacoum toxicosis.
AB  - Thymic cysts with pseudoepitheliomatous hyperplasia are described in a 7-month
      old female American Eskimo Dog that died of complications from brodifacoum
      poisoning. Grossly, there was hemothorax with marked cranial mediastinal
      hemorrhage. Histologically, thymic lobules were expanded and distorted by
      irregular cysts, lined by single to multiple layers of plump to slightly
      attenuated polygonal squamous epithelial cells supported by a basement membrane
      (pseudoepitheliomatous hyperplasia). The thymus had a paucity of lymphocytes and
      lacked corticomedullary differentiation. Extensive hemorrhage within the cysts
      and thymic parenchyma extended into the adjacent adipose tissue. To the authors'
      knowledge, this is the first report of cystic thymic degeneration with
      pseudoepitheliomatous hyperplasia in a nonhuman species.

PMID- 19176510
TI  - Immunohistochemical expression of p63 and deltaNp63 in mixed tumors of canine
      mammary glands and its relation with p53 expression.
AB  - The immunohistochemical expression of p63, DeltaNp63, and p53 was studied in
      mixed tumors of canine mammary glands (13 benign mixed tumors and 19 carcinomas
      arising from benign mixed tumors) to determine the role of p63 and its isoform
      DeltaNp63 in the development of mixed tumors, as well as to assess its relation
      with p53. P63 was expressed in myoepithelial cells of all benign mixed tumors and
      in 18 of 19 carcinomas in mixed tumors. The p63-negative carcinoma in mixed
      tumors was invasive, and a loss of p63 was detected in the other malignant tumors
      showing a discontinuous p63-stained myoepithelial layer. DeltaNp63 was expressed
      in all benign mixed tumors but only in p63-positive carcinomas in mixed tumors.
      Despite its positive correlation with p63 expression in carcinomas in mixed
      tumors (r = 0.8323, P < .00001), DeltaNp63 expression showed a decrease in benign
      tumors. Positivity for p53 was detected in 2 of 13 and 1 of 19 benign mixed
      tumors and carcinomas in mixed tumors, respectively. There was no correlation
      between p63 or DeltaNp63 and p53 expression. Our data support the notion that the
      decrease of p63 expression, in particular of its isoform DeltaNp63, seems to be
      an important factor in the development of carcinomas in mixed tumors.

PMID- 19176511
TI  - Copper-associated hepatitis in Labrador Retrievers.
AB  - Labrador Retrievers with elevated hepatic copper levels have been reported;
      however, it is unclear whether primary copper-associated hepatitis occurs in this
      breed. The objective of this study was to determine whether copper-associated
      hepatitis could be identified in Labradors by reviewing cases from the Diagnostic
      Center for Population and Animal Health, Michigan State University. Sixteen
      Labrador Retrievers (3 male, 12 female, and 1 of undetermined sex) between 4 and
      11 years old, had multifocal and coalescing, centrilobular hepatitis
      characterized by macrophages with abundant intracytoplasmic copper and
      hemosiderin. Other lesions included multifocal, centrilobular and random,
      pigmented granulomas, hepatocellular necrosis, intrahepatic cholestasis,
      centrilobular or bridging fibrosis, and occasionally, pseudolobule formation. In
      rhodanine-stained sections, copper was concentrated in the cytoplasm of
      centrilobular and midzonal hepatocytes and in macrophages, which is consistent
      with copper-associated hepatitis. In 12 of the dogs, quantitative liver copper
      levels were available, and in all but 2 dogs the levels were greater than 2,000
      parts per million dry weight (ppm dw). One dog had a liver copper level of 1,990
      ppm dw and one dog with advanced hepatic cirrhosis had a level of 1,490 ppm dw.
      The findings suggest that primary copper-associated hepatitis likely occurs in
      Labrador Retrievers.

PMID- 19176512
TI  - Freedom of materials.
AB  - Despite the best policies, shared data and materials often come with so many
      strings attached that they are essentially unusable. Furthermore, a Catch-22
      exists for academic scientists who must disclose structural data at the time of
      publication of the biological effects of a small molecule, because, armed with
      the structure, commercial entities can rapidly make and patent related molecules,
      thus hampering academic research. Although companies that publish original
      research are bound by the data- and material-sharing policies of journals, in
      practice they may legally restrict use and access once molecules are patented.

PMID- 19176514
TI  - Grab your partner with both hands: cytoskeletal remodeling by Arp2/3 signaling.
AB  - The seemingly simple structure of the actin filament belies the elaborate
      signaling pathways that regulate its assembly and disassembly in eukaryotic
      cells. In retrospect, this signaling complexity should not be surprising. Actin
      regulates many dynamic cellular processes, including protein and organelle
      trafficking, establishment of cell polarity, directional migration, cellular
      traction, and the efficiency of endocytosis. Signaling events that coordinately
      control actin turnover during these processes must display a high degree of
      sophistication. Emerging data on an important regulator of actin dynamics, the
      actin-related protein 2 and 3 (Arp2/3) complex, suggest a model of how this may
      occur.

PMID- 19176515
TI  - Direct response to Notch activation: signaling crosstalk and incoherent logic.
AB  - Notch is the receptor in one of a small group of conserved signaling pathways
      that are essential at multiple stages in development. Although the mechanism of
      transduction impinges directly on the nucleus to regulate transcription through
      the CSL [CBF-1/Su(H)/LAG-1] [corrected] DNA binding protein, there are few known
      direct target genes. Thus, relatively little is known about the immediate
      cellular consequences of Notch activation. We therefore set out to determine the
      genome-wide response to Notch activation by analyzing the changes in messenger
      RNA (mRNA) expression and the sites of CSL occupancy within 30 minutes of
      activating Notch in Drosophila cells. Through combining these data, we identify
      high-confidence direct targets of Notch that are implicated in the maintenance of
      adult muscle progenitors in vivo. These targets are enriched in cell
      morphogenesis genes and in components of other cell signaling pathways,
      especially the epidermal growth factor receptor (EGFR) pathway. Also evident are
      examples of incoherent network logic, where Notch stimulates the expression of
      both a gene and the repressor of that gene, which may result in a transient
      window of competence after Notch activation. Furthermore, because targets
      comprise both positive and negative regulators, cells become poised for both
      outcomes, suggesting one mechanism through which Notch activation can lead to
      opposite effects in different contexts.

PMID- 19176516
TI  - Differential requirement of mTOR in postmitotic tissues and tumorigenesis.
AB  - The mammalian target of rapamycin (mTOR) is a crucial effector in a complex
      signaling network commonly disrupted in cancer. mTOR exerts its multiple
      functions in the context of two different multiprotein complexes: mTOR complex 1
      (mTORC1) and mTOR complex 2 (mTORC2). Loss of the tumor suppressor PTEN
      (phosphatase and tensin homolog deleted from chromosome 10) can hyperactivate
      mTOR through AKT and represents one of the most frequent events in human prostate
      cancer. We show here that conditional inactivation of mTor in the adult mouse
      prostate is seemingly inconsequential for this postmitotic tissue. Conversely,
      inactivation of mTor leads to a marked suppression of Pten loss-induced tumor
      initiation and progression in the prostate. This suppression is more pronounced
      than that elicited by the sole pharmacological abrogation of mTORC1. Acute
      inactivation of mTor in vitro also highlights the differential requirement of
      mTor function in proliferating and transformed cells. Collectively, our data
      constitute a strong rationale for developing specific mTOR inhibitors targeting
      both mTORC1 and mTORC2 for the treatment of tumors triggered by PTEN deficiency
      and aberrant mTOR signaling.

PMID- 19176517
TI  - Characterization of the intrinsic and TSC2-GAP-regulated GTPase activity of Rheb
      by real-time NMR.
AB  - Tuberous sclerosis complex 2 (TSC2), whose gene is frequently mutated in tuberous
      sclerosis, increases the guanosine triphosphatase (GTPase) activity of the small
      heterotrimeric GTP-binding protein (G protein) Rheb, thus resulting in the
      decreased activity of the mammalian target of rapamycin (mTOR), the master
      regulator of cell growth. Here, we describe the development of a nuclear magnetic
      resonance (NMR)-based, quantitative, real-time assay to explore the molecular
      mechanism of the intrinsic and TSC2-catalyzed GTPase activity of Rheb. We
      confirmed that TSC2 accelerated GTP hydrolysis by Rheb 50-fold through an
      "asparagine-thumb" mechanism to substitute for the nonfunctional "catalytic"
      glutamine of Rheb and we determined that catalysis was enthalpy driven. Most, but
      not all, of the disease-associated GTPase-activating protein (GAP) domain mutants
      of TSC2 that we examined affected its enzymatic activity. This method can now be
      applied to study the function and regulation of other GTPases.

PMID- 19176518
TI  - EGFR signals to mTOR through PKC and independently of Akt in glioma.
AB  - Amplification of the gene encoding the epidermal growth factor (EGF) receptor
      (EGFR) occurs commonly in glioblastoma, leading to activation of downstream
      kinases including phosphatidylinositol 3'-kinase (PI3K), Akt, and mammalian
      target of rapamycin (mTOR). Here, we show that phosphorylation of mTOR and its
      downstream substrate rpS6 (ribosomal protein S6) are robust biomarkers for the
      antiproliferative effect of EGFR inhibitors. Inhibition of EGFR signaling
      correlated with decreased abundance of phosphorylated mTOR (p-mTOR) and rpS6 (p
      rpS6) in cells wild type for the gene encoding PTEN (phosphatase and tensin
      homolog on chromosome 10), a negative regulator of PI3K. In contrast, inhibition
      of EGFR signaling failed to affect p-mTOR or p-rpS6 in cells mutant for PTEN,
      which are resistant to EGFR inhibitors. Although the abundance of phosphorylated
      Akt (p-Akt) decreased in response to inhibition of EGFR signaling, Akt was
      dispensable for signaling between EGFR and mTOR. We identified an Akt-independent
      pathway linking EGFR to mTOR that was critically dependent on protein kinase C
      (PKC). Consistent with these observations, the abundance of EGFR generally
      correlated with phosphorylation of rpS6 and PKC in primary human glioblastoma
      tumors, and correlated poorly with phosphorylation of Akt. Inhibition of PKC led
      to decreased viability of glioma cells regardless of PTEN or EGFR status,
      suggesting that PKC inhibitors should be tested in glioma. These findings
      underline the importance of signaling between EGFR and mTOR in glioma, identify
      PKCalpha as essential to this network, and question the necessity of Akt as a
      critical intermediate coupling EGFR and mTOR in glioma.

PMID- 19176519
TI  - A complex-based reconstruction of the Saccharomyces cerevisiae interactome.
AB  - Most cellular processes are performed by proteomic units that interact with each
      other. These units are often stoichiometrically stable complexes comprised of
      several proteins. To obtain a faithful view of the protein interactome we must
      view it in terms of these basic units (complexes and proteins) and the
      interactions between them. This study makes two contributions toward this goal.
      First, it provides a new algorithm for reconstruction of stable complexes from a
      variety of heterogeneous biological assays; our approach combines state-of-the
      art machine learning methods with a novel hierarchical clustering algorithm that
      allows clusters to overlap. We demonstrate that our approach constructs over 40%
      more known complexes than other recent methods and that the complexes it produces
      are more biologically coherent even compared with the reference set. We provide
      experimental support for some of our novel predictions, identifying both a new
      complex involved in nutrient starvation and a new component of the eisosome
      complex. Second, we provide a high accuracy algorithm for the novel problem of
      predicting transient interactions involving complexes. We show that our complex
      level network, which we call ComplexNet, provides novel insights regarding the
      protein-protein interaction network. In particular, we reinterpret the finding
      that "hubs" in the network are enriched for being essential, showing instead that
      essential proteins tend to be clustered together in essential complexes and that
      these essential complexes tend to be large.

PMID- 19176520
TI  - Molecular mechanisms of thioredoxin and glutaredoxin as hydrogen donors for
      Mammalian s phase ribonucleotide reductase.
AB  - Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in
      deoxyribonucleotide synthesis essential for DNA replication and repair. RNR in S
      phase mammalian cells comprises a weak cytosolic complex of the catalytic R1
      protein containing redox active cysteine residues and the R2 protein harboring
      the tyrosine free radical. Each enzyme turnover generates a disulfide in the
      active site of R1, which is reduced by C-terminally located shuttle dithiols
      leaving a disulfide to be reduced. Electrons for reduction come ultimately from
      NADPH via thioredoxin reductase and thioredoxin (Trx) or glutathione reductase,
      glutathione, and glutaredoxin (Grx), but the mechanism has not been clarified for
      mammalian RNR. Using recombinant mouse RNR, we found that Trx1 and Grx1 had
      similar catalytic efficiency (k(cat)/K(m)). With 4 mm GSH, Grx1 showed a higher
      affinity (apparent K(m) value, 0.18 microm) compared with Trx1 which displayed a
      higher apparent k(cat), suggesting its major role in S phase DNA replication.
      Surprisingly, Grx activity was strongly dependent on GSH concentrations (apparent
      K(m) value, 3 mm) and a Grx2 C40S mutant was active despite only one cysteine
      residue in the active site. This demonstrates a GSH-mixed disulfide mechanism for
      glutaredoxin catalysis in contrast to the dithiol mechanism for thioredoxin. This
      may be an advantage with the low levels of RNR for DNA repair or in tumor cells
      with high RNR and no or low Trx expression. Our results demonstrate mechanistic
      differences between the mammalian and canonical Escherichia coli RNR enzymes,
      which may offer an explanation for the nonconserved shuttle dithiol sequences in
      the C terminus of the R1.

PMID- 19176521
TI  - Protein phosphatase 5 regulates the function of 53BP1 after neocarzinostatin
      induced DNA damage.
AB  - 53BP1 (p53-binding protein 1) is a conserved nuclear protein that is
      phosphorylated in response to DNA damage and rapidly recruited to the site of DNA
      double strand breaks, demonstrating its role in the early events to DNA damage
      and repair of damaged DNA. In this study, we used the yeast two-hybrid system to
      identify proteins that interact with 53BP1. Identification and characterization
      of 53BP1 protein interactions may help to further elucidate the function and
      regulation of 53BP1. We identified protein phosphatase 5 (PP5), a
      serine/threonine phosphatase that has been implicated in multiple cellular
      function, as a 53BP1-binding protein. This interaction further confirmed that
      53BP1 interacts with PP5 in PP5-overexpressing U2OS cells, after radiomimetic
      agent neocarzinostatin (NCS) treatment. 53BP1 dephosphorylation at Ser-25 and Ser
      1778 was accelerated in PP5-overexpressing U2OS cells following NCS treatment,
      and its dephosphorylation was correlated with reduced phospho-53BP1 foci
      formation. In contrast, the overexpression of PP5 had no effect on NCS-activated
      BRCA1-Ser-1524 phosphorylation. Additionally, PP5 down-regulation inhibited the
      dephosphorylation of 53BP1 on Ser-1778 and the disappearance of phospho-53BP1
      foci following NCS treatment. Moreover, non-homologous end-joining activity was
      reduced in PP5-overexpressing U2OS cells. These findings indicate that PP5 plays
      an important role in the regulation of 53BP1 phosphorylation and activity in
      vivo.

PMID- 19176522
TI  - Structural and functional analysis of transmembrane XI of the NHE1 isoform of the
      Na+/H+ exchanger.
AB  - The Na(+)/H(+) exchanger isoform 1 is a ubiquitously expressed integral membrane
      protein that regulates intracellular pH in mammals by extruding an intracellular
      H(+) in exchange for one extracellular Na(+). We characterized structural and
      functional aspects of the critical transmembrane (TM) segment XI (residues 449
      470) by using cysteine scanning mutagenesis and high resolution NMR. Each residue
      of TM XI was mutated to cysteine in the background of the cysteine-less protein
      and the sensitivity to water-soluble sulfhydryl reactive compounds MTSET ((2
      (trimethylammonium) ethyl)methanethiosulfonate) and MTSES ((2-sulfonatoethyl)
      methanethiosulfonate) was determined for those residues with at least moderate
      activity remaining. Of the residues tested, only proteins with mutations L457C,
      I461C, and L465C were inhibited by MTSET. The activity of the L465C mutant was
      almost completely eliminated, whereas that of the L457C and I461C mutants was
      partially affected. The structure of a peptide representing TM XI (residues
      Lys(447)-Lys(472)) was determined using high resolution NMR spectroscopy in
      dodecylphosphocholine micelles. The structure consisted of helical regions
      between Asp(447)-Tyr(454) and Phe(460)-Lys(471) at the N and C termini of the
      peptide, respectively, connected by a region with poorly defined, irregular
      structure consisting of residues Gly(455)-Gly(459). TM XI of NHE1 had a
      structural similarity to TM XI of the Escherichia coli Na(+)/H(+) exchanger NhaA.
      The results suggest that TM XI is a discontinuous helix, with residue Leu(465)
      contributing to the pore.

PMID- 19176523
TI  - Sulfiredoxin Translocation into Mitochondria Plays a Crucial Role in Reducing
      Hyperoxidized Peroxiredoxin III.
AB  - The mitochondria are the major intracellular source of reactive oxygen species
      (ROS), which are generated during cellular respiration. The role of peroxiredoxin
      (Prx) III, a 2-Cys Prx family member, in the scavenging of mitochondrial H(2)O(2)
      has recently been emphasized. While eliminating H(2)O(2), Prx can become
      overoxidized and inactivated by modifying the active cysteine into cysteine
      sulfinic acid (Cys-SO(2)H). When 2-Cys Prxs are inactivated in vitro,
      sulfiredoxin (Srx) reduces the cysteine sulfinic acid to cysteines. However,
      whereas Srx is localized in the cytoplasm, Prx III is present exclusively in the
      mitochondria. Although Srx reduces sulfinic Prx III in vitro, it remains unclear
      whether the reduction of Prx III in cells is actually mediated by Srx. Our gain-
      and loss-of-function experiments show that Srx is responsible for reducing not
      only sulfinic cytosolic Prxs (I and II) but also sulfinic mitochondrial Prx III.
      We further demonstrate that Srx translocates from the cytosol to mitochondria in
      response to oxidative stress. Overexpression of mitochondrion-targeted Srx
      promotes the regeneration of sulfinic Prx III and results in cellular resistance
      to apoptosis, with enhanced elimination of mitochondrial H(2)O(2) and decreased
      rates of mitochondrial membrane potential collapse. These results indicate that
      Srx plays a crucial role in the reactivation of sulfinic mitochondrial Prx III
      and that its mitochondrial translocation is critical in maintaining the balance
      between mitochondrial H(2)O(2) production and elimination.

PMID- 19176524
TI  - Characterization of the Functionally Critical AXAXAXA and PXXEXXP Motifs of the
      ATP Synthase c-Subunit from an Alkaliphilic Bacillus.
AB  - The membrane-embedded rotor in the F(0) sector of proton-translocating ATP
      synthases is formed from hairpin-like c-subunits that are protonated and
      deprotonated during energization of ATP synthesis. This study focuses on two c
      subunit motifs that are unique to synthases of extremely alkaliphilic Bacillus
      species. One motif is the AXAXAXA sequence found in the N-terminal helix-1
      instead of the GXGXGXG of non-alkaliphiles. Quadruple A-->G chromosomal mutants
      of alkaliphilic Bacillus pseudofirmus OF4 retain 50% of the wild-type hydrolytic
      activity (ATPase) but <18% of the ATP synthase capacity at high pH. Consistent
      with a structural impact of the four alanine replacements, the mutant ATPase
      activity showed enhanced inhibition by dicyclohexylcarbodiimide, which blocks the
      helix-2 carboxylate. Single, double, or triple A-->G mutants exhibited more
      modest defects, as monitored by malate growth. The key carboxylate is in the
      second motif, which is P(51)XXE(54)XXP in extreme alkaliphiles instead of the
      (A/G)XX(E/D)XXP found elsewhere. Mutation of Pro(51) to alanine had been shown to
      severely reduce malate growth and ATP synthesis at high pH. Here, two Pro(51) to
      glycine mutants of different severities retained ATP synthase capacity but
      exhibited growth deficits and proton leakiness. A Glu(54) to Asp(54) change
      increased proton leakiness and reduced malate growth 79-90%. The Pro(51) and the
      Glu(54) mutants were both more dicyclohexylcarbodiimide-sensitive than wild type.
      The results highlight the requirement for c-subunit adaptations to achieve
      alkaliphile ATP synthesis with minimal cytoplasmic proton loss and suggest
      partial suppression of some mutations by changes outside the atp operon.

PMID- 19176525
TI  - Phosphorylation of Activation Transcription Factor-2 at Serine 121 by Protein
      Kinase C Controls c-Jun-mediated Activation of Transcription.
AB  - Activation transcription factor-2 (ATF-2) is phosphorylated by various protein
      kinases, such as JNK/p38/ERK, calmodulin kinase IV, protein kinase A, and protein
      kinase C (PKC), in response to a variety of stimuli. However, the role of the
      phosphorylation of ATF-2 by PKC in vivo in the transcriptional control of genes
      that include the activation protein-1 (AP-1)/cyclic AMP-response element remains
      to be defined. Using antibodies against the phosphorylated serine residue
      (Ser(P)) at position 121 of ATF-2, we have demonstrated that PKC phosphorylates
      ATF-2 at Ser-121 and that phosphorylation of Ser-121 (to yield ATF-2pS121)
      becomes detectable at the late stage of the response of HeLa cells to 12-O
      tetradecanoylphorbol-13-acetate (TPA) and is maintained for more than 2 h. By
      contrast, phosphorylation of ATF-2 at threonine residues 69 and 71 (Thr-69/71, to
      yield ATF-2pT69/71) and at Ser-340 and Ser-367 (to yield ATF-2pS340 and ATF
      2pS367) is detectable as an immediate early response. Unlike levels of ATF
      2pT69/71 and ATF-2pS340, the level of ATF-2pS121 increases in the nuclei of HeLa
      cells in response to TPA. A serine-to-alanine mutation at position 121 of ATF-2
      represses the c-Jun-dependent transcription of AP-1/cyclic AMP-response element
      reporter genes and also the p300-mediated activation of a Gal4-reporter gene in
      response to TPA. Our results suggest that the phosphorylation of ATF-2 at Ser-121
      plays a key role in the c-Jun-mediated activation of transcription that occurs in
      response to TPA.

PMID- 19176526
TI  - Role of phosphorylation and basic residues in the catalytic domain of cytosolic
      phospholipase A2alpha in regulating interfacial kinetics and binding and cellular
      function.
AB  - Group IVA cytosolic phospholipase A(2) (cPLA(2)alpha) is regulated by
      phosphorylation and calcium-induced translocation to membranes. Immortalized
      mouse lung fibroblasts lacking endogenous cPLA(2)alpha (IMLF(-/-)) were
      reconstituted with wild type and cPLA(2)alpha mutants to investigate how calcium,
      phosphorylation, and the putative phosphatidylinositol 4,5-bisphosphate (PIP(2))
      binding site regulate translocation and arachidonic acid (AA) release. Agonists
      that elicit distinct modes of calcium mobilization were used. Serum induced
      cPLA(2)alpha translocation to Golgi within seconds that temporally paralleled the
      initial calcium transient. However, the subsequent influx of extracellular
      calcium was essential for stable binding of cPLA(2)alpha to Golgi and AA release.
      In contrast, phorbol 12-myristate 13-acetate induced low amplitude calcium
      oscillations, slower translocation of cPLA(2)alpha to Golgi, and much less AA
      release, which were blocked by chelating extracellular calcium. AA release from
      IMLF(-/-) expressing phosphorylation site (S505A) and PIP(2) binding site
      (K488N/K543N/K544N) mutants was partially reduced compared with cells expressing
      wild type cPLA(2)alpha, but calcium-induced translocation was not impaired.
      Consistent with these results, Ser-505 phosphorylation did not change the calcium
      requirement for interfacial binding and catalysis in vitro but increased activity
      by 2-fold. Mutations in basic residues in the catalytic domain of cPLA(2)alpha
      reduced activation by PIP(2) but did not affect the concentration of calcium
      required for interfacial binding or phospholipid hydrolysis. The results
      demonstrate that Ser-505 phosphorylation and basic residues in the catalytic
      domain principally act to regulate cPLA(2)alpha hydrolytic activity.

PMID- 19176527
TI  - The Carboxyl-terminal Domain of RNA Polymerase II Is Not Sufficient to Enhance
      the Efficiency of Pre-mRNA Capping or Splicing in the Context of a Different
      Polymerase.
AB  - Eukaryotic messenger RNA precursors (pre-mRNAs) synthesized by RNA polymerase II
      (RNAP II) are processed co-transcriptionally. The carboxyl-terminal domain (CTD)
      of the largest subunit of RNA polymerase II is thought to mediate the coupling of
      transcription with pre-mRNA processing by coordinating the recruitment of
      processing factors during synthesis of nascent transcripts. Previous studies have
      demonstrated that the phosphorylated CTD is required for efficient co
      transcriptional processing. In the study presented here we investigated whether
      the CTD is sufficient to coordinate transcription with pre-mRNA capping and
      splicing in the context of two other DNA-dependent RNA polymerases, mammalian
      RNAP III and bacteriophage T7 RNAP. Our results indicate that the CTD fused to
      the largest subunit of RNAP III (POLR3A) is not sufficient to enhance co
      transcriptional pre-mRNA splicing or capping in vivo. Additionally, we analyzed a
      T7 RNAP-CTD fusion protein and examined its ability to enhance pre-mRNA splicing
      and capping of both constitutively and alternatively spliced substrates. We
      observed that the CTD in the context of T7 RNAP was not sufficient to enhance pre
      mRNA splicing or capping either in vitro or in vivo. We propose that the
      efficient coupling of transcription to pre-mRNA processing requires not only the
      phosphorylated CTD but also other RNAP II specific subunits or associated
      factors.

PMID- 19176528
TI  - Voltage-gated Sodium Channel Activity Promotes Cysteine Cathepsin-dependent
      Invasiveness and Colony Growth of Human Cancer Cells.
AB  - Voltage-gated sodium channels (Na(V)) are functionally expressed in highly
      metastatic cancer cells derived from nonexcitable epithelial tissues (breast,
      prostate, lung, and cervix). MDA-MB-231 breast cancer cells express functional
      sodium channel complexes, consisting of Na(V)1.5 and associated auxiliary beta
      subunits, that are responsible for a sustained inward sodium current at the
      membrane potential. Although these channels do not regulate cellular
      multiplication or migration, their inhibition by the specific blocker
      tetrodotoxin impairs both the extracellular gelatinolytic activity (monitored
      with DQ-gelatin) and cell invasiveness leading to the attenuation of colony
      growth and cell spreading in three-dimensional Matrigel-composed matrices. MDA-MB
      231 cells express functional cysteine cathepsins, which we found play a
      predominant role ( approximately 65%) in cancer invasiveness. Matrigel invasion
      is significantly decreased in the presence of specific inhibitors of cathepsins B
      and S (CA-074 and Z-FL-COCHO, respectively), and co-application of tetrodotoxin
      does not further reduce cell invasion. This suggests that cathepsins B and S are
      involved in invasiveness and that their proteolytic activity partly depends on
      Na(V) function. Inhibiting Na(V) has no consequence for cathepsins at the
      transcription, translation, and secretion levels. However, Na(V) activity leads
      to an intracellular alkalinization and a perimembrane acidification favorable for
      the extracellular activity of these acidic proteases. We propose that Na(v)
      enhance the invasiveness of cancer cells by favoring the pH-dependent activity of
      cysteine cathepsins. This general mechanism could lead to the identification of
      new targets allowing the therapeutic prevention of metastases.

PMID- 19176529
TI  - Post-transcriptional Regulation of Genes Encoding Anti-microbial Peptides in
      Drosophila.
AB  - Secretion of antimicrobial peptides (AMPep) is a central defense mechanism used
      by invertebrates to combat infections. In Drosophila the synthesis of these
      peptides is a highly regulated process allowing their rapid release in the
      hemolymph upon contact with pathogens and the arrest of their production after
      pathogen clearance. We observed that AMPep genes have either a transient or
      sustained expression profile in S2 Drosophila cells treated with peptidoglycan.
      Moreover, AMPep genes containing AU-rich elements (ARE) in their 3'-untranslated
      region (UTR) are subject to a post-transcriptional control affecting mRNA
      stability, thereby contributing to their transient expression profile. Cecropin
      A1 (CecA1) constitutes the prototype of this latter class of AMPeps. CecA1 mRNA
      bears in its 3'-UTR an ARE similar to class II AREs found in several short-lived
      mammalian mRNAs. In response to immune deficiency cascade signaling activated by
      Gram-negative peptidoglycans, CecA1 mRNA is transiently stabilized and
      subsequently submitted to deadenylation and decay mediated by the ARE present in
      its 3'-UTR. The functionality of CecA1 ARE relies on its ability to recruit TIS11
      protein, which accelerates CecA1 mRNA deadenylation and decay. Moreover, we
      observed that CecA1 mRNA deadenylation is a biphasic process. Whereas early
      deadenylation is independent of TIS11, the later deadenylation phase depends on
      TIS11 and is mediated by CAF1 deadenylase. We also report that in contrast to
      tristetraprolin, its mammalian homolog, TIS11, is constitutively expressed in S2
      cells and accumulates in cytoplasmic foci distinct from processing bodies,
      suggesting that the Drosophila ARE-mediated mRNA deadenylation and decay
      mechanism is markedly different in invertebrates and mammals.

PMID- 19176530
TI  - Oxidative Stress Increases the Number of Stress Granules in Senescent Cells and
      Triggers a Rapid Decrease in p21waf1/cip1 Translation.
AB  - Very little is known as to how the accumulation of senescent cells during aging
      may affect our ability to cope with various stresses. Here we show that the
      assembly of stress granules (SGs) is part of the early events used by senescent
      cells to respond to certain stresses. Although SGs can form in response to stress
      during senescence activation, their number significantly increases once the cells
      are fully senescent. This increase correlates with a rapid decrease in the
      expression levels of the cyclin kinase inhibitor p21, an important activator of
      senescence. Throughout stress, p21 mRNA is stabilized and localizes to SGs, but
      only during late senescence does this localization interferes with its
      translation. Additionally, we observed that when the stress is relieved,
      senescent cells produce lower levels of p21 protein, which correlates with a
      small delay in SG disassembly. Therefore, our data suggest that SG formation and
      the reduction in p21 protein levels represent two main events by which senescent
      cells respond to stress.

PMID- 19176531
TI  - Location of the retinal chromophore in the activated state of rhodopsin*.
AB  - Rhodopsin is a highly specialized G protein-coupled receptor (GPCR) that is
      activated by the rapid photochemical isomerization of its covalently bound 11-cis
      retinal chromophore. Using two-dimensional solid-state NMR spectroscopy, we
      defined the position of the retinal in the active metarhodopsin II intermediate.
      Distance constraints were obtained between amino acids in the retinal binding
      site and specific (13)C-labeled sites located on the beta-ionone ring, polyene
      chain, and Schiff base end of the retinal. We show that the retinal C20 methyl
      group rotates toward the second extracellular loop (EL2), which forms a cap on
      the retinal binding site in the inactive receptor. Despite the trajectory of the
      methyl group, we observed an increase in the C20-Gly(188) (EL2) distance
      consistent with an increase in separation between the retinal and EL2 upon
      activation. NMR distance constraints showed that the beta-ionone ring moves to a
      position between Met(207) and Phe(208) on transmembrane helix H5. Movement of the
      ring toward H5 was also reflected in increased separation between the Cepsilon
      carbons of Lys(296) (H7) and Met(44) (H1) and between Gly(121) (H3) and the
      retinal C18 methyl group. Helix-helix interactions involving the H3-H5 and H4-H5
      interfaces were also found to change in the formation of metarhodopsin II
      reflecting increased retinal-protein interactions in the region of Glu(122) (H3)
      and His(211) (H5). We discuss the location of the retinal in metarhodopsin II and
      its interaction with sequence motifs, which are highly conserved across the
      pharmaceutically important class A GPCR family, with respect to the mechanism of
      receptor activation.

PMID- 19176532
TI  - Mechanisms of resistance of hepatocyte retinoid X receptor alpha-null mice to WY
      14,643-induced hepatocyte proliferation and cholestasis.
AB  - Peroxisome proliferators, such as the lipid-lowering fibrates that function as
      agonists for peroxisome proliferator-activated receptor alpha (PPARalpha), induce
      liver tumors in rodents and may produce cholestasis in humans. Considerable
      attention has focused on peroxisome proliferator-induced hepatocellular
      carcinoma, a phenomenon not noted in man, whereas limited studies examine
      fibrates and other therapeutic drugs that induce cholestasis, a common finding in
      humans. Moreover, the mechanisms by which fibrates induce hepatocyte
      proliferation and cholestasis are still not fully understood. We have examined
      the role of hepatocyte retinoid X receptor alpha (RXRalpha), an essential partner
      of PPARalpha, in modulating WY-14,643-induced hepatocyte proliferation and
      cholestasis. WY-14,643 treatment induced hepatomegaly in wild type (WT) mice that
      was also accompanied by induction of the expression of cyclins D1, D3, A2, and B1
      and Cdc2 as well as inhibition of Wee 1. Such changes were either absent or
      greatly reduced in hepatocyte RXRalpha-null mice. Furthermore, neither WY-14,643
      treatment nor RXRalpha deficiency affected apoptosis, indicating the importance
      of PPARalpha/RXRalpha in regulating Wee 1-mediated Cdc2/cyclin B1 expression for
      cells to enter into mitosis. WY-14,643 treatment also induced cholestasis and
      liver injury, which is evidenced by induction of alanine aminotransferase,
      alkaline phosphatase, and hepatic bile acid levels in WT mice. Hepatocyte
      RXRalpha deficiency protected the mice from WY-14,643-induced liver injury. WY
      14,643-mediated induction of the small heterodimer partner, Mrp3, and Cyp3a11
      levels was greater in hepatocyte RXRalpha-null than in WT mouse livers suggesting
      enhanced repression of bile acid synthesis and increased efflux of bile acids
      into blood for renal excretion as well as hydroxylation of bile acids because of
      hepatocyte RXRalpha deficiency. These data establish a crucial role of hepatocyte
      RXRalpha in regulating WY-14,643-mediated cell cycle progression as well as bile
      acid homeostasis.

PMID- 19176534
TI  - Antepartum continuous epidural ropivacaine therapy reduces uterine artery
      vascular resistance in pre-eclampsia: a randomized, dose-ranging, placebo
      controlled study.
AB  - BACKGROUND: No therapy is currently available to improve the reduced
      uteroplacental blood flow (UPBF) that characterizes pre-eclampsia. We
      hypothesized that sympathectomy induced by epidural local anaesthesia reduces
      uterine vascular resistance (which is inversely correlated with UPBF) in pre
      eclampsia. METHODS: Ten pregnant women between 24 and 32 weeks of gestation with
      pre-eclampsia and uterine artery flow abnormalities were randomized to antepartum
      continuous epidural therapy (ACET) or control. ACET was initiated by a 5 day dose
      ranging trial (ACET-1) of 0.04, 0.06, 0.08, and 0.1% ropivacaine and saline
      placebo, each at 10 ml h(-1) for 24 h. Doses were randomized and double-blind.
      Doppler ultrasound indices of vascular resistance were assessed at baseline and
      after each 24 h dosing period in both uterine arteries. Subsequently, these ACET
      patients were administered 0.1% ropivacaine until delivery (ACET-2), with one
      additional randomized double-blind placebo day. RESULTS: Five patients were
      randomized to ACET. In each patient, one uterine artery exhibited a dose
      dependent reduction in vascular resistance (P=0.035), a response that returned to
      baseline following placebo (P<0.001). The contralateral uterine artery exhibited
      either increased vascular resistance or no change. In all cases, the uterine
      artery that responded to ACET had higher baseline resistance than its pair
      (P=0.043). Baseline right-left difference in resistance between paired uterine
      arteries was greatly diminished following ACET. Although ACET patients had a mean
      (sd) duration to delivery of 19 (9) days compared with control 2 (1) days
      (P=0.008), this should be interpreted with caution because of demographic
      differences between groups. CONCLUSIONS: ACET reduces uterine artery resistance
      in pre-eclampsia <32 weeks. Uteroplacental re-distribution is a novel observation
      and warrants further investigation.

PMID- 19176535
TI  - Cardiovascular flashlight. Mycotic aneurysm of the ascending aorta: an unusual
      infectious complication of left ventricular assist device explantation.

PMID- 19176533
TI  - Structural determinants of integrin binding to the talin rod.
AB  - The adaptor protein talin serves both to activate the integrin family of cell
      adhesion molecules and to couple integrins to the actin cytoskeleton. Integrin
      activation has been shown to involve binding of the talin FERM domain to membrane
      proximal sequences in the cytoplasmic domain of the integrin beta-subunit.
      However, a second integrin-binding site (IBS2) has been identified near the C
      terminal end of the talin rod. Here we report the crystal structure of IBS2
      (residues 1974-2293), which comprises two five-helix bundles, "IBS2-A" (1974
      2139) and "IBS2-B" (2140-2293), connected by a continuous helix with a distinct
      kink at its center that is stabilized by side-chain H-bonding. Solution studies
      using small angle x-ray scattering and NMR point to a fairly flexible quaternary
      organization. Using pull-down and enzyme-linked immunosorbent assays, we
      demonstrate that integrin binding requires both IBS2 domains, as does binding to
      acidic phospholipids and robust targeting to focal adhesions. We have defined the
      membrane proximal region of the integrin cytoplasmic domain as the major binding
      region, although more membrane distal regions are also required for strong
      binding. Alanine-scanning mutagenesis points to an important electrostatic
      component to binding. Thermal unfolding experiments show that integrin binding
      induces conformational changes in the IBS2 module, which we speculate are linked
      to vinculin and membrane binding.

PMID- 19176536
TI  - Tissue Doppler echocardiography in persons with hypertension, diabetes, or
      ischaemic heart disease: the Copenhagen City Heart Study.
AB  - AIMS: To test the hypothesis that echocardiographic tissue Doppler imaging (TDI)
      reveals reduced myocardial function in hypertension, diabetes, and ischaemic
      heart disease (IHD) in the general population. METHODS AND RESULTS: Within a
      large, community-based population study, cardiac function was evaluated in 1036
      participants by both conventional echocardiography and colour TDI. Peak systolic
      (s') and early diastolic (e') velocities, longitudinal displacement (LD), and the
      ratio of mitral inflow E-wave to e' (E/e') were measured. TDI revealed
      significantly impaired parameters of systolic and diastolic cardiac function in
      hypertension [n = 345; LD 10.1 (+/-standard deviation, SD 2.0 mm), P < 0.001;
      E/e' 12.4 (x/SD 1.4), P < 0.001], diabetes [n = 65; LD 9.8 (+/-SD 2.2 mm), P <
      0.001; E/e' 12.7 (x/SD 1.5), P < 0.001], and IHD [n = 93; LD 9.4 (+/-SD 2.5 mm),
      P < 0.001; E/e' 13.0 (x/SD 1.5), P < 0.001] compared with controls [n = 533; LD
      11.4 (+/-SD 2.0 mm); E/e' 9.0 (x/SD 1.3)]. This pattern remained significant
      after adjusting for age, sex, body mass index, heart rate, and the results of
      conventional echocardiography. CONCLUSION: In the general population, persons
      with hypertension, diabetes, or IHD have impaired cardiac function by TDI
      independently of the result of conventional echocardiography.

PMID- 19176537
TI  - Stroke in paroxysmal atrial fibrillation: report from the Stockholm Cohort of
      Atrial Fibrillation.
AB  - AIMS: Knowledge about stroke risk in paroxysmal atrial fibrillation (PxAF) is
      limited. Although current guideline recommendations advocate the same treatment
      as in permanent atrial fibrillation (PermAF), most patients with PxAF do not
      receive prophylactic anticoagulation. The aim of this study is to investigate
      whether there are differences in stroke risk between PxAF and PermAF. METHODS AND
      RESULTS: All patients with PxAF (n = 855) and PermAF (n = 1126) treated for
      atrial fibrillation (AF) during 2002 at one of Scandinavia's largest hospitals
      were followed-up for 3.6 years regarding incidence of stroke. Information about
      type of AF, comorbidity, medication, and clinical events during follow-up was
      acquired from medical records and the National Register of Hospital Discharges.
      The incidence of ischaemic stroke was similar in PxAF and PermAF (26 vs. 29
      events/1000 patient years). The multivariable-adjusted hazard ratio (HR) for
      ischaemic stroke in PxAF compared with PermAF was 1.07 (95% CI 0.71-1.61) in
      subjects without prior stroke. The corresponding HR for any stroke, ischaemic or
      haemorrhagic, was 0.89 (95% CI 0.61-1.30). Compared with the general population,
      ischaemic stroke was twice as common as expected in PxAF after standardization
      for age and sex (standardized incidence ratio 2.12, 95% CI 1.52-2.71). PxAF
      patients who took warfarin had approximately half as many ischaemic strokes as
      those who did not take warfarin (HR 0.44, 95% CI 0.30-0.65). CONCLUSION:
      Ischaemic stroke is about as common in PxAF as in PermAF, and about twice as
      common as in the general population. Yet, PxAF patients do not receive protective
      anticoagulant treatment as often as patients with PermAF do. It is therefore
      important to increase the use of anticoagulants among PxAF patients in accordance
      with current guideline recommendations.

PMID- 19176538
TI  - Changes in management of elderly patients with myocardial infarction.
AB  - AIMS: Despite being at higher risk for mortality, elderly patients (>/=75 years)
      admitted for acute myocardial infarction (MI) often receive fewer effective
      therapies, because of contraindications or higher risk of drug-induced adverse
      events. The aim of this study was to assess the changes in the use of effective
      treatments between 2001 and 2006 in elderly patients, and the relation with 1
      month mortality. METHODS AND RESULTS: Prospective, multicentre registry,
      considering two periods: 6 months between October 2000 and March 2001 (cohort 1)
      and 12 months between October 2005 and October 2006 (cohort 2). Demographic and
      clinical characteristics at admission, in-hospital treatment (reperfusion or
      early invasive therapy, oral antiplatelets, anticoagulants, angiotensin
      converting enzyme (ACE)-inhibitors, beta-blockers, and statins), and 1-month
      survival were compared between the two cohorts, after adjustment on a propensity
      score (for being admitted in 2001). Eight hundred and sixty-eight elderly
      patients were included, 280 in cohort 1 and 588 in cohort 2. When compared with
      cohort 1, patients from cohort 2 presented with comparable characteristics,
      except for the Global Registry of Acute Coronary Events risk score and we
      observed a significant increase in the use of aspirin, clopidogrel, reperfusion
      therapy, ACE-inhibitors, and statins in cohort 2. One-month mortality was
      significantly lower in cohort 2 (13.6% in cohort 1 vs. 7.1% in cohort 2, P =
      0.001), mainly driven by a decrease in the mortality among patients with ST
      segment elevation MI (23.3% in cohort 1 vs. 9.2% in cohort 2, P < 0.001).
      Adjustment on the propensity score did not alter these results. By multivariable
      analysis, the three-fold higher mortality in patients from cohort 1 was offset
      when the rate of use of treatments was considered in the model, suggesting that
      the treatment intensity was related to lower mortality. CONCLUSION: Between 2001
      and 2006, a significant increase in the use of guidelines-recommended treatments
      (GRTs) was observed, associated with lower 30-day mortality, in elderly patients.
      These data confirm that high-risk patients, such as the elderly, benefit from an
      increase in the use of GRTs.

PMID- 19176539
TI  - Chronic obstructive pulmonary disease is an independent predictor of death but
      not atherosclerotic events in patients with myocardial infarction: analysis of
      the Valsartan in Acute Myocardial Infarction Trial (VALIANT).
AB  - AIMS: Chronic obstructive pulmonary disease is an independent predictor of
      mortality in patients with myocardial infarction (MI). However, the impact on
      mode of death and risk of atherosclerotic events is unknown. METHODS AND RESULTS:
      We assessed the risk of death and major cardiovascular (CV) events associated
      with chronic obstructive pulmonary disease in 14 703 patients with acute MI
      enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) trial. Cox
      proportional hazards models were used to evaluate the relationship between
      chronic obstructive pulmonary disease and CV outcomes. A total of 1258 (8.6%)
      patients had chronic obstructive pulmonary disease. Over a median follow-up
      period of 24.7 months, all-cause mortality was 30% in patients with chronic
      obstructive pulmonary disease, compared with 19% in those without. The adjusted
      hazard ratio (HR) for mortality was 1.14 (95% confidence interval 1.02-1.28).
      This reflected increased incidence of both non-CV death [HR 1.86 (1.43-2.42)] and
      sudden death [HR 1.26 (1.03-1.53)]. The unadjusted risk of all pre-specified CV
      outcomes was increased. However, after multivariate adjustment, chronic
      obstructive pulmonary disease was not an independent predictor of atherosclerotic
      events [MI or stroke: HR 0.98 (0.77-1.23)]. Mortality was significantly lower in
      patients receiving beta-blockers, irrespective of airway disease. CONCLUSION: In
      high-risk patients with acute MI, chronic obstructive pulmonary disease is
      associated with increased mortality and non-fatal clinical events (both CV and
      non-CV). However, patients with chronic obstructive pulmonary disease did not
      experience a higher rate of atherosclerotic events.

PMID- 19176540
TI  - Maternal levels of perfluorinated chemicals and subfecundity.
AB  - BACKGROUND: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are
      ubiquitous man-made compounds that are possible hormonal disruptors. We examined
      whether exposure to these compounds may decrease fecundity in humans. METHODS:
      Plasma levels of PFOS and PFOA were measured at weeks 4-14 of pregnancy among
      1240 women from the Danish National Birth Cohort recruited from 1996 to 2002. For
      this pregnancy, women reported time to pregnancy (TTP) in five categories (<1, 1
      2, 3-5, 6-12 and >12 months). Infertility was defined as having a TTP of >12
      months or received infertility treatment to establish this pregnancy. RESULTS:
      Longer TTP was associated with higher maternal levels of PFOA and PFOS (P <
      0.001). Compared with women in the lowest exposure quartile, the adjusted odds of
      infertility increased by 70-134 and 60-154% among women in the higher three
      quartiles of PFOS and PFOA, respectively. Fecundity odds ratios (FORs) were also
      estimated using Cox discrete-time models. The adjusted FORs were virtually
      identical for women in the three highest exposure groups of PFOS (FOR = 0.70,
      0.67 and 0.74, respectively) compared with the lowest quartile. A linear-like
      trend was observed for PFOA (FOR = 0.72, 0.73 and 0.60 for three highest
      quartiles versus lowest quartile). When all quartiles were included in a
      likelihood ratio test, the trends were significant for PFOS and PFOA (P = 0.002
      and P < 0.001, respectively). CONCLUSIONS: These findings suggest that PFOA and
      PFOS exposure at plasma levels seen in the general population may reduce
      fecundity; such exposure levels are common in developed countries.

PMID- 19176541
TI  - Anxiety and depression have no influence on the cancellation and pregnancy rates
      of a first IVF or ICSI treatment.
AB  - BACKGROUND: After many years of research, the impact of psychological distress on
      the IVF treatment outcome is still unclear. This study aimed to determine the
      influences of anxiety and depression before and during IVF or ICSI treatment on
      the cancellation and pregnancy rates of inductees. METHODS: In a multicentre
      prospective cohort study, we assessed anxiety and depression at baseline and the
      procedural anxiety level one day before oocyte retrieval, with the short versions
      of the State Anxiety Inventory (STAI) and the Beck Depression Inventory-Primary
      Care (BDI-PC). The effect of baseline anxiety and depression on the cancellation
      and pregnancy rates of 783 women in their first IVF or ICSI treatment was
      evaluated. We also determined if a change in anxiety from the start of treatment
      until just before oocyte retrieval affects the pregnancy rate. The predictive
      value of distress was assessed while controlling for several factors in
      subfertility treatment. RESULTS: Neither baseline nor procedural anxiety, nor
      depression affected the ongoing pregnancy rates, with odds ratios (ORs) of 1.04
      (95% CI 0.82-1.33), 0.96 (95% CI 0.77-1.20) and 0.85 (95% CI 0.65-1.10),
      respectively. Neither did the anxiety gain score affect the pregnancy rate, OR
      1.08 (95% CI 0.83-1.41). A cancellation of treatment could not be predicted by
      either anxiety or depression, OR 1.16 (95% CI 0.83-1.63) and 0.85 (95% CI 0.59
      1.22), respectively. CONCLUSIONS: Inductees in IVF treatment can be reassured
      that anxiety and depression levels before and during treatment have no
      significant influence on the cancellation and pregnancy rates.

PMID- 19176542
TI  - In GnRH antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on
      the day of oocyte retrieval correlates with altered gene expression.
AB  - BACKGROUND: Previously, advanced endometrial maturation on the day of oocyte
      retrieval in GnRH antagonist and -agonist IVF cycles was observed. In these
      cycles, endometrial advancement exceeding 3 days between the histological dating
      and the cycle day never resulted in an ongoing clinical pregnancy. In this study,
      the gene expression of human endometrium on the day of oocyte retrieval in GnRH
      antagonist/rec-FSH cycles was analyzed, in correlation with the morphological
      dating. METHODS: Biopsies were taken on the day of oocyte retrieval in 47
      patients with 1 or 2 embryos replaced on Day 3 in the same cycle. Endometrial
      dating was performed according to Noyes' criteria. Biopsies from 11 patients were
      analyzed for gene expression with the Affymetrix HG U133 Plus 2 microarray. Data
      analysis, clustering and pathway analysis were performed with GCOS, GeneSpring
      7.3 and Ingenuity, respectively. RESULTS: According to Noyes' criteria, all
      endometria taken on the day of oocyte retrieval showed an advanced maturation,
      ranging from +d2 to +d4. The patients with a subsequent clinical pregnancy all
      showed a histological dating corresponding to +d2 or +d3. When comparing
      endometria +d2-3 to +d4, the microarray results showed a differential expression
      of 2550 probe sets. Significantly up-regulated genes were SERPINB6, FOXO3A, SOX17
      and CDC42. Down-regulated genes of interest were NRP1, HOXA10 and OSF2. Principal
      component analysis and hierarchical clustering demonstrated two distinct
      clusters. CONCLUSIONS: In stimulated cycles, endometrial gene expression on the
      day of oocyte retrieval discriminates between women with and without
      histologically advanced endometrial maturation exceeding 3 days and supports
      histological dating results by Noyes' criteria.

PMID- 19176543
TI  - Effect of asoprisnil on uterine proliferation markers and endometrial expression
      of the tumour suppressor gene, PTEN.
AB  - BACKGROUND: The selective progesterone receptor modulator asoprisnil suppresses
      uterine bleeding and decreases leiomyoma volume while maintaining follicular
      phase estrogen concentrations. For safety of potential clinical applications, any
      proliferative effect of asoprisnil on uterine tissues, particularly endometrium,
      needs to be established. METHODS: In a double-blind, randomized, placebo
      controlled study (continuation of previously published trial No. NCT00150644
      (Williams et al., 2007 and Wilkens et al., 2008)), 33 patients with symptomatic
      uterine leiomyomata received placebo, 10 or 25 mg asoprisnil daily for 12 weeks
      before hysterectomy. Proliferation markers Ki-67 and anti-phospho-histone H3
      (PH3) were immunolocalized in endometrium, myometrium and leiomyoma tissue.
      Endometrial PTEN (phosphatase and tensin homologue, a tumour suppressor gene)
      expression was also assessed by immunohistochemistry. PH3-positive glandular and
      stromal cells were counted per measured endometrial area. Endometrial Ki-67
      expression was assessed using stereological methods. Stained myometrial and
      leiomyoma cells were counted per 10 fields (x250). PTEN immunostaining was
      quantified using a histoscore. Each asoprisnil group was compared with placebo
      (secretory phase) with significance at 0.05 level. RESULTS: Endometrial
      epithelial proliferation and PTEN expression were not significantly different
      between placebo and asoprisnil groups. Decreased stromal Ki-67 expression (P <
      0.05) suggested any effect of asoprisnil on endometrial proliferation to be
      inhibitory. Immunolocalization of PTEN expression was not different between
      treatment groups in any tissue compartments. Myometrial Ki-67 expression
      decreased following asoprisnil 25 mg (P < 0.05). CONCLUSIONS: Asoprisnil does not
      induce proliferation of uterine tissues and does not suppress endometrial PTEN
      expression.

PMID- 19176544
TI  - Brain function decline in healthy retired athletes who sustained their last
      sports concussion in early adulthood.
AB  - Recent studies have shown that the detrimental effects of sports concussions on
      cognitive and motor function may persist up to a few years post-injury. The
      present study sought to investigate the effects of having sustained a sports
      concussion more than 30 years prior to testing on cognitive and motor functions.
      Nineteen healthy former athletes, in late adulthood (mean age = 60.79; SD =
      5.16), who sustained their last sport-related concussion in early adulthood (mean
      age = 26.05; SD = 9.21) were compared with 21 healthy former athletes with no
      history of concussion (mean age = 58.89; SD = 9.07). Neuropsychological tests
      sensitive to age-related changes in cognition were administered. An auditory
      oddball paradigm was used to evoke P3a and P3b brain responses. Four TMS
      paradigms were employed to assess motor cortex excitability: (i) resting motor
      threshold; (ii) paired-pulse intracortical inhibition and intracortical
      facilitation; (iii) input/output curve and (iv) cortical silent period (CSP). A
      rapid alternating movement task was also used to characterize motor system
      dysfunctions. Relative to controls, former athletes with a history of concussion
      had: (i) lower performance on neuropsychological tests of episodic memory and
      response inhibition; (ii) significantly delayed and attenuated P3a/P3b
      components; (iii) significantly prolonged CSP and (iv) significantly reduced
      movement velocity (bradykinesia). The finding that the P3, the CSP as well as
      neuropsychological and motor indices were altered more than three decades post
      concussion provides evidence for the chronicity of cognitive and motor system
      changes consecutive to sports concussion.

PMID- 19176545
TI  - Comparison of interferon {gamma} release assays and conventional screening tests
      before tumour necrosis factor {alpha} blockade in patients with inflammatory
      arthritis.
AB  - OBJECTIVE: To compare the performance of two interferon gamma release assays
      (IGRAs) and conventional screening tests in patients with inflammatory arthritis
      undergoing screening for latent tuberculosis infection (LTBI) before treatment
      with anti-tumour necrosis factor alpha (anti-TNFalpha) compounds. METHODS:
      Successive patients were subjected to conventional LTBI screening, including a
      tuberculin skin test (TST). The T-SPOT.TB test was performed on all patients and
      the QuantiFERON-TB Gold test was performed on a large subset. The results of the
      IGRAs were compared with the results of conventional screening tests. RESULTS: A
      total 150 patients were evaluated. The majority (57.9%) had rheumatoid arthritis.
      Previous vaccination with Bacille Calmette-Guerin was confirmed in 82% of
      patients. No patient had received prior anti-TB treatment. A total of 57 patients
      (38.0%) had at least one positive conventional risk factor. In contrast, an
      unequivocally positive T-SPOT.TB test was seen in only 14/143 (9.8%). There was
      98.2% agreement between the two IGRAs. Statistically significant associations
      were found between each of the IGRAs and both TST and risk history, but not chest
      x-ray (CXR). A positive IGRA result was significantly associated with increased
      age. TB was not reactivated in any patient during the follow-up period.
      INTERPRETATION: This study suggests that IGRAs may be useful when screening for
      LTBI before anti-TNFalpha therapy in patients with immune-mediated inflammatory
      diseases. The observations reported here also highlight the inadequate
      performance of CXR as a marker of LTBI.

PMID- 19176546
TI  - KEA: kinase enrichment analysis.
AB  - MOTIVATION: Multivariate experiments applied to mammalian cells often produce
      lists of proteins/genes altered under treatment versus control conditions. Such
      lists can be projected onto prior knowledge of kinase-substrate interactions to
      infer the list of kinases associated with a specific protein list. By computing
      how the proportion of kinases, associated with a specific list of proteins/genes,
      deviates from an expected distribution, we can rank kinases and kinase families
      based on the likelihood that these kinases are functionally associated with
      regulating the cell under specific experimental conditions. Such analysis can
      assist in producing hypotheses that can explain how the kinome is involved in the
      maintenance of different cellular states and can be manipulated to modulate cells
      towards a desired phenotype. SUMMARY: Kinase enrichment analysis (KEA) is a web
      based tool with an underlying database providing users with the ability to link
      lists of mammalian proteins/genes with the kinases that phosphorylate them. The
      system draws from several available kinase-substrate databases to compute kinase
      enrichment probability based on the distribution of kinase-substrate proportions
      in the background kinase-substrate database compared with kinases found to be
      associated with an input list of genes/proteins. AVAILABILITY: The KEA system is
      freely available at http://amp.pharm.mssm.edu/lib/kea.jsp

PMID- 19176547
TI  - A novel meta-analysis method exploiting consistency of high-throughput
      experiments.
AB  - MOTIVATION: Large-scale biological experiments provide snapshots into the huge
      number of processes running in parallel within the organism. These processes
      depend on a large number of (hidden) (epi)genetic, social, environmental and
      other factors that are out of experimentalists' control. This makes it extremely
      difficult to identify the dominant processes and the elements involved in them
      based on a single experiment. It is therefore desirable to use multiple sets of
      experiments targeting the same phenomena while differing in some experimental
      parameters (hidden or controllable). Although such datasets are becoming
      increasingly common, their analysis is complicated by the fact that the various
      biological elements could be influenced by different sets of factors. RESULTS:
      The central hypothesis of this article is that biologically related elements and
      processes are affected by changes in similar ways while unrelated ones are
      affected differently. Thus, the relations between related elements are more
      consistent across experiments. The method outlined here looks for groups of
      elements with robust intra-group relationships in the expectation that they are
      related. The major groups of elements may be identified in this way. The
      strengths of relationships per se are not valued, just their consistency. This
      represents a completely novel and unutilized source of information. In the
      analysis of time course microarray experiments, I found cell cycle- and ribosome
      related genes to be the major groups. Despite not looking for these groups in
      particular, the identification of these genes rivals that of methods designed
      specifically for this purpose. AVAILABILITY: A C++ implementation is available at
      http://www.rinst.org/ICS/ICS_Programs.tar.gz.

PMID- 19176548
TI  - Benchmarks for identification of ordinary differential equations from time series
      data.
AB  - MOTIVATION: In recent years, the biological literature has seen a significant
      increase of reported methods for identifying both structure and parameters of
      ordinary differential equations (ODEs) from time series data. A natural way to
      evaluate the performance of such methods is to try them on a sufficient number of
      realistic test cases. However, weak practices in specifying identification
      problems and lack of commonly accepted benchmark problems makes it difficult to
      evaluate and compare different methods. RESULTS: To enable better evaluation and
      comparisons between different methods, we propose how to specify identification
      problems as optimization problems with a model space of allowed reactions (e.g.
      reaction kinetics like Michaelis-Menten or S-systems), ranges for the parameters,
      time series data and an error function. We also define a file format for such
      problems. We then present a collection of more than 40 benchmark problems for ODE
      model identification of cellular systems. The collection includes realistic
      problems of different levels of difficulty w.r.t. size and quality of data. We
      consider both problems with simulated data from known systems, and problems with
      real data. Finally, we present results based on our identification algorithm for
      all benchmark problems. In comparison with publications on which we have based
      some of the benchmark problems, our approach allows all problems to be solved
      without the use of supercomputing. AVAILABILITY: The benchmark problems are
      available at www.odeidentification.org. SUPPLEMENTARY INFORMATION: Supplementary
      data are available at Bioinformatics online.

PMID- 19176549
TI  - Genome-wide association analysis by lasso penalized logistic regression.
AB  - MOTIVATION: In ordinary regression, imposition of a lasso penalty makes
      continuous model selection straightforward. Lasso penalized regression is
      particularly advantageous when the number of predictors far exceeds the number of
      observations. METHOD: The present article evaluates the performance of lasso
      penalized logistic regression in case-control disease gene mapping with a large
      number of SNPs (single nucleotide polymorphisms) predictors. The strength of the
      lasso penalty can be tuned to select a predetermined number of the most relevant
      SNPs and other predictors. For a given value of the tuning constant, the
      penalized likelihood is quickly maximized by cyclic coordinate ascent. Once the
      most potent marginal predictors are identified, their two-way and higher order
      interactions can also be examined by lasso penalized logistic regression.
      RESULTS: This strategy is tested on both simulated and real data. Our findings on
      coeliac disease replicate the previous SNP results and shed light on possible
      interactions among the SNPs. AVAILABILITY: The software discussed is available in
      Mendel 9.0 at the UCLA Human Genetics web site. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 19176550
TI  - Automated procedure for candidate compound selection in GC-MS metabolomics based
      on prediction of Kovats retention index.
AB  - MOTIVATION: Matching both the retention index (RI) and the mass spectrum of an
      unknown compound against a mass spectral reference library provides strong
      evidence for a correct identification of that compound. Data on retention indices
      are, however, available for only a small fraction of the compounds in such
      libraries. We propose a quantitative structure-RI model that enables the ranking
      and filtering of putative identifications of compounds for which the predicted RI
      falls outside a predefined window. RESULTS: We constructed multiple linear
      regression and support vector regression (SVR) models using a set of descriptors
      obtained with a genetic algorithm as variable selection method. The SVR model is
      a significant improvement over previous models built for structurally diverse
      compounds as it covers a large range (360-4100) of RI values and gives better
      prediction of isomer compounds. The hit list reduction varied from 41% to 60% and
      depended on the size of the original hit list. Large hit lists were reduced to a
      greater extend compared with small hit lists. AVAILABILITY:
      http://appliedbioinformatics.wur.nl/GC-MS. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 19176551
TI  - QMSim: a large-scale genome simulator for livestock.
AB  - SUMMARY: QMSim was designed to simulate large-scale genotyping data in multiple
      and complex livestock pedigrees. The simulation is basically carried out in two
      steps. In the first step, a historical population is simulated to establish
      mutation-drift equilibrium, and in the second step, recent population structures
      are generated, which can be very complex. A wide variety of genome architectures,
      ranging from infinitesimal model to single-locus model, can be simulated. The
      program is efficient in terms of computing time and memory requirements.
      AVAILABILITY: Executable versions of QMSim for Windows and Linux are freely
      available at http://www.aps.uoguelph.ca/~msargol/qmsim/.

PMID- 19176552
TI  - Serial dilution curve: a new method for analysis of reverse phase protein array
      data.
AB  - Reverse phase protein arrays (RPPAs) are a powerful high-throughput tool for
      measuring protein concentrations in a large number of samples. In RPPA
      technology, the original samples are often diluted successively multiple times,
      forming dilution series to extend the dynamic range of the measurements and to
      increase confidence in quantitation. An RPPA experiment is equivalent to running
      multiple ELISA assays concurrently except that there is usually no known protein
      concentration from which one can construct a standard response curve. Here, we
      describe a new method called 'serial dilution curve for RPPA data analysis'.
      Compared with the existing methods, the new method has the advantage of using
      fewer parameters and offering a simple way of visualizing the raw data. We showed
      how the method can be used to examine data quality and to obtain robust
      quantification of protein concentrations. AVAILABILITY: A computer program in R
      for using serial dilution curve for RPPA data analysis is freely available at
      http://odin.mdacc.tmc.edu/~zhangli/RPPA.

PMID- 19176553
TI  - Testing significance relative to a fold-change threshold is a TREAT.
AB  - MOTIVATION: Statistical methods are used to test for the differential expression
      of genes in microarray experiments. The most widely used methods successfully
      test whether the true differential expression is different from zero, but give no
      assurance that the differences found are large enough to be biologically
      meaningful. RESULTS: We present a method, t-tests relative to a threshold
      (TREAT), that allows researchers to test formally the hypothesis (with associated
      p-values) that the differential expression in a microarray experiment is greater
      than a given (biologically meaningful) threshold. We have evaluated the method
      using simulated data, a dataset from a quality control experiment for microarrays
      and data from a biological experiment investigating histone deacetylase
      inhibitors. When the magnitude of differential expression is taken into account,
      TREAT improves upon the false discovery rate of existing methods and identifies
      more biologically relevant genes. AVAILABILITY: R code implementing our methods
      is contributed to the software package limma available at
      http://www.bioconductor.org.

PMID- 19176554
TI  - Fragment-based identification of druggable 'hot spots' of proteins using Fourier
      domain correlation techniques.
AB  - MOTIVATION: The binding sites of proteins generally contain smaller regions that
      provide major contributions to the binding free energy and hence are the prime
      targets in drug design. Screening libraries of fragment-sized compounds by NMR or
      X-ray crystallography demonstrates that such 'hot spot' regions bind a large
      variety of small organic molecules, and that a relatively high 'hit rate' is
      predictive of target sites that are likely to bind drug-like ligands with high
      affinity. Our goal is to determine the 'hot spots' computationally rather than
      experimentally. RESULTS: We have developed the FTMAP algorithm that performs
      global search of the entire protein surface for regions that bind a number of
      small organic probe molecules. The search is based on the extremely efficient
      fast Fourier transform (FFT) correlation approach which can sample billions of
      probe positions on dense translational and rotational grids, but can use only
      sums of correlation functions for scoring and hence is generally restricted to
      very simple energy expressions. The novelty of FTMAP is that we were able to
      incorporate and represent on grids a detailed energy expression, resulting in a
      very accurate identification of low-energy probe clusters. Overlapping clusters
      of different probes are defined as consensus sites (CSs). We show that the
      largest CS is generally located at the most important subsite of the protein
      binding site, and the nearby smaller CSs identify other important subsites.
      Mapping results are presented for elastase whose structure has been solved in
      aqueous solutions of eight organic solvents, and we show that FTMAP provides very
      similar information. The second application is to renin, a long-standing
      pharmaceutical target for the treatment of hypertension, and we show that the
      major CSs trace out the shape of the first approved renin inhibitor, aliskiren.
      AVAILABILITY: FTMAP is available as a server at http://ftmap.bu.edu/.

PMID- 19176556
TI  - Parallelized prediction error estimation for evaluation of high-dimensional
      models.
AB  - There is a multitude of new techniques that promise to extract predictive
      information in bioinformatics applications. It has been recognized that a first
      step for validation of the resulting model fits should rely on proper use of
      resampling techniques. However, this advice is frequently not followed, potential
      reasons being difficulty of correct implementation and computational demand. This
      is addressed by the R package peperr, which is designed for reliable prediction
      error estimation through resampling, potentially accelerated by parallel
      execution on a compute cluster. Its interface allows easy connection to newly
      developed model fitting routines. Performance evaluation of the latter is
      furthermore guided by diagnostic plots, which helps to detect specific problems
      due to high-dimensional data structures. AVAILABILITY: http://cran.r-project.org,
      http://www.imbi.uni-freiburg.de/parallel. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 19176557
TI  - The DICS repository: module-assisted analysis of disease-related gene lists.
AB  - SUMMARY: The DICS database is a dynamic web repository of computationally
      predicted functional modules from the human protein-protein interaction network.
      It provides references to the CORUM, DrugBank, KEGG and Reactome pathway
      databases. DICS can be accessed for retrieving sets of overlapping modules and
      protein complexes that are significantly enriched in a gene list, thereby
      providing valuable information about the functional context. AVAILABILITY:
      Supplementary information on datasets and methods is available on the web server
      http://mips.gsf.de/proj/dics.

PMID- 19176555
TI  - A flexible rank-based framework for detecting copy number aberrations from array
      data.
AB  - MOTIVATION: DNA copy number aberration--both inherited and sporadic--is a
      significant contributor to a variety of human diseases. Copy number
      characterization is therefore an area of intense research. Probe hybridization
      based arrays are important tools used to measure copy number in a high-throughput
      manner. RESULTS: In this article, we present a simple but powerful nonparametric
      rank-based approach to detect deletions and gains from raw array copy number
      measurements. We use three different rank-based statistics to detect three
      separate molecular phenomena-somatic lesions, germline deletions and germline
      gains. The approach is robust and rigorously grounded in statistical theory,
      thereby enabling the meaningful assignment of statistical significance to each
      putative aberration. We demonstrate the flexibility of our approach by applying
      it to data from three different array platforms. We show that our method compares
      favorably with established approaches by applying it to published well
      characterized samples. Power simulations demonstrate exquisite sensitivity for
      array data of reasonable quality. CONCLUSIONS: Our flexible rank-based framework
      is suitable for multiple platforms including single nucleotide polymorphism
      arrays and array comparative genomic hybridization, and can reliably detect gains
      or losses of genomic DNA, whether inherited, de novo, or somatic. AVAILABILITY:
      An R package RankCopy containing the methods described here, and is freely
      available from the author's web site
      (http://mendel.gene.cwru.edu/laframboiselab/). SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 19176558
TI  - Retention time alignment algorithms for LC/MS data must consider non-linear
      shifts.
AB  - MOTIVATION: Proteomics has particularly evolved to become of high interest for
      the field of biomarker discovery and drug development. Especially the combination
      of liquid chromatography and mass spectrometry (LC/MS) has proven to be a
      powerful technique for analyzing protein mixtures. Clinically orientated
      proteomic studies will have to compare hundreds of LC/MS runs at a time. In order
      to compare different runs, sophisticated preprocessing steps have to be
      performed. An important step is the retention time (rt) alignment of LC/MS runs.
      Especially non-linear shifts in the rt between pairs of LC/MS runs make this a
      crucial and non-trivial problem. RESULTS: For the purpose of demonstrating the
      particular importance of correcting non-linear rt shifts, we evaluate and compare
      different alignment algorithms. We present and analyze two versions of a new
      algorithm that is based on regression techniques, once assuming and estimating
      only linear shifts and once also allowing for the estimation of non-linear
      shifts. As an example for another type of alignment method we use an established
      alignment algorithm based on shifting vectors that we adapted to allow for
      correcting non-linear shifts also. In a simulation study, we show that rt
      alignment procedures that can estimate non-linear shifts yield clearly better
      alignments. This is even true under mild non-linear deviations. AVAILABILITY: R
      code for the regression-based alignment methods and simulated datasets are
      available at http://www.statistik.tu-dortmund.de/genetik-publikationen
      alignment.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 19176559
TI  - A novel comprehensive wave-form MS data processing method.
AB  - MOTIVATION: Mass spectrometry (MS) can generate high-throughput protein profiles
      for biomedical research to discover biologically related protein
      patterns/biomarkers. The noisy functional MS data collected by current
      technologies, however, require consistent, sensitive and robust data-processing
      techniques for successful biomedical application. Therefore, it is important to
      detect features precisely for each spectrum, quantify them well and assign a
      unique label to features from the same protein/peptide across spectra. RESULTS:
      In this article, we propose a new comprehensive MS data preprocessing package,
      Wave-spec, which includes several novel algorithms. It can overcome several
      conventional difficulties. Wave-spec can be applied to multiple types of MS data
      generated with different MS technologies. Results from this new package were
      evaluated and compared to several existing approaches based on a MALDI-TOF MS
      dataset. AVAILABILITY: An example of MATLAB scripts used to implement the methods
      described in this article, along with Supplementary Figures, can be found at
      http://www.vicc.org/biostatistics/supp.php. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 19176560
TI  - Fast computation of neighbor seeds.
AB  - MOTIVATION: Alignment of biological sequences is one of the most frequently
      performed computer tasks. The current state of the art involves the use of
      (multiple) spaced seeds for producing high quality alignments. A particular
      important class is that of neighbor seeds which combine high sensitivity with
      reduced space requirements. Current algorithms for computing good neighbor seeds
      are very slow (exponential). RESULTS: We give a polynomial-time heuristic
      algorithm that computes better neighbor seeds than previous ones while being
      several orders of magnitude faster.

PMID- 19176562
TI  - Prevention of atrial fibrillation: another good reason to recommend statins to
      women?

PMID- 19176564
TI  - Right ventricular acrylic cement embolism: late complication of percutaneous
      vertebroplasty.

PMID- 19176561
TI  - Statin use is associated with lower risk of atrial fibrillation in women with
      coronary disease: the HERS trial.
AB  - OBJECTIVE: To determine the efficacy of statin treatment in atrial fibrillation
      (AF) prevention in women. DESIGN: Cohort study using data obtained in the Heart
      and Estrogen/Progestin Replacement Study (HERS). SETTING: Secondary analysis of a
      multicentre, randomised controlled clinical trial. PATIENTS: 2673 Postmenopausal
      women with coronary disease. MAIN OUTCOME MEASURES: AF prevalence at baseline and
      incident AF over a mean follow-up of 4.1 years. RESULTS: 88 Women with AF were
      identified: 29 at baseline and 59 during follow-up. Women with AF were
      significantly less likely to be taking a statin at study enrollment than those
      without AF (22% vs 37%, p = 0.003). Baseline statin use was associated with a 65%
      lower odds of having AF at baseline after controlling for age, race, history of
      myocardial infarction or revascularisation and history of heart failure (odds
      ratio 0.35, 95% confidence interval (CI) 0.13 to 0.93, p = 0.04). The risk of
      developing AF during the study among those free from AF at baseline, adjusted for
      the same covariates, was 55% less for those receiving statin treatment (hazard
      ratio 0.45, 95% CI 0.26 to 0.78, p = 0.004). CONCLUSIONS: Statin treatment is
      associated with a lower prevalence and incidence of AF after adjustment for
      potential confounders in postmenopausal women with coronary disease.

PMID- 19176565
TI  - Intracardiac echocardiography.
AB  - Intracardiac echocardiography (ICE) is increasingly being used to guide
      percutaneous interventional procedures, principally the closure of interatrial
      septal abnormalities, and to support electrophysiological procedures. Clear views
      of intracardiac structures can help a number of other procedures, such as
      myocardial biopsy and paravalvular leak closure. The main advantages of ICE over
      transoesophageal echocardiography during closure of atrial septal defects are
      that the use of ICE eliminates the need for a general anaesthetic, affords
      clearer imaging, shorter procedure times and reduces hospital stays and radiation
      doses. The principal disadvantage is the additional cost of the catheter, though
      this can be offset by improved turnaround times and reduced personnel costs.

PMID- 19176566
TI  - Positron emission tomography (PET): a new tool in the diagnosis of endocarditis.

PMID- 19176568
TI  - Thiazolidinediones and cardiovascular outcomes in type 2 diabetes.

PMID- 19176569
TI  - Permanent pacemaker implantation technique: part II.

PMID- 19176570
TI  - Rectal chlamydia--a reservoir of undiagnosed infection in men who have sex with
      men.
AB  - OBJECTIVE: To determine the prevalence of rectal chlamydia infection in a cohort
      of men who have sex with men (MSM) and the proportion of infection that would be
      missed without routine screening. METHODS: MSM presenting to four HIV/GUM
      outpatient clinics at the Chelsea & Westminster Hospital NHS Foundation Trust
      between 1 November 2005 and 29 September 2006 were offered testing for rectal
      chlamydia infection in addition to their routine screen for sexually transmitted
      infections (STIs). Chlamydia trachomatis (CT) tests were performed using the
      Beckton-Dickinson Probe-Tec Strand Displacement Assay. Positive samples were re
      tested at the Sexually Transmitted Bacteria Reference Laboratory, to confirm the
      result and identify lymphogranuloma venereum (LGV)-associated serovars. RESULTS:
      A total of 3076 men were screened. We found an 8.2% prevalence of infection with
      CT (LGV and non-LGV serovars) in the rectum and 5.4% in the urethra. The HIV and
      rectal chlamydia co-infection rate was 38.1%. The majority of rectal infections
      (69.2%, (171/247)) were asymptomatic and would have been missed if routine
      screening had not been undertaken. Of the samples re-tested, 94.2% (227/242)
      rectal and 91.8% (79/86) urethral specimens were confirmed CT positive and 36
      cases of LGV were identified. CONCLUSION: Our data show a high rate of rectal
      chlamydia infection, in the majority of cases it was asymptomatic. We recommend
      routine screening for rectal chlamydia in men at risk, as this may represent an
      important reservoir for the onward transmission of infection.

PMID- 19176571
TI  - Giant VAC in a patient with extensive necrotizing fasciitis.
AB  - The authors present a case of an extensive fulminant necrotizing fasciitis of the
      left flank, thigh, and lower parts of the leg treated with debridement, split
      thickness skin grafting, and a giant negative pressure wound dressing covering
      0.53 m( 2) or 18% of the body surface. To the authors' knowledge, this is the
      largest split-thickness grafted body surface successfully treated with negative
      pressure wound dressing documented in the literature.

PMID- 19176572
TI  - Prevalence of COPD in primary care: no room for complacency.

PMID- 19176573
TI  - Different effects of aluminum on the actin cytoskeleton and brefeldin A-sensitive
      vesicle recycling in root apex cells of two maize varieties differing in root
      elongation rate and aluminum tolerance.
AB  - A relationship between aluminum (Al) toxicity, endocytosis, endosomes and vesicle
      recycling in the root transition zone has recently been demonstrated. Here the
      importance of filamentous actin (F-actin)-based vesicle trafficking for Al
      tolerance has been investigating in maize varieties differing in their Al
      sensitivities. More Al was internalized into root tip cells of the Al-sensitive
      variety 16x36 than in the Al-tolerant variety Cateto. The actin cytoskeleton and
      vesicle trafficking were primary targets for Al toxicity in the root tips of the
      sensitive variety. Visualization of boron-cross-linked rhamnogalacturonan II
      (RGII)-containing brefeldin A (BFA) compartments revealed that Al inhibited the
      formation of these compartments, especially in variety 16x36. The time sequence
      of Al effects on pectin recycling matches the growth effects of Al in this
      sensitive variety. These results support the hypothesis that Al binding to pectin
      rich cell walls can contribute to reversible inhibition of root elongation. Al
      induced alterations on F-actin were most evident in the central part of the
      transition zone of Al-sensitive 16x36, where Al was localized inside the
      nucleoli. In relation to this observation, a role for symplastic Al in both
      irreversible growth inhibition and amelioration of BFA-induced inhibition of root
      elongation is discussed.

PMID- 19176574
TI  - Electrodermal reactivity to emotion processing in adults with autistic spectrum
      disorders.
AB  - Although alterations of emotion processing are recognized as a core component of
      autism, the level at which alterations occur is still debated. Discrepant results
      suggest that overt assessment of emotion processing is not appropriate. In this
      study, skin conductance response (SCR) was used to examine covert emotional
      processes. Both behavioural responses and SCRs of 16 adults with an autistic
      spectrum disorder (ASD) were compared to those of 16 typical matched adults.
      Participants had to judge emotional facial expressions, the age of faces or the
      direction of a moving object. Although behavioural performance was similar in the
      two populations, individuals with an ASD exhibited lower SCRs than controls in
      the emotional judgement task. This suggests that such individuals may rely on
      different strategies due to altered autonomic processing. Furthermore, failure to
      produce normal physiological reactions to emotional faces may be related to
      social impairments in individuals with an ASD.

PMID- 19176575
TI  - 'Hath charms to soothe . . .': an exploratory study of how high-functioning
      adults with ASD experience music.
AB  - Semi-structured interviews were conducted with 12 high-functioning adults on the
      autism spectrum, in order to examine the nature of their personal experiences of
      music. Consistent with the literature on typically developing people's engagement
      with music, the analysis showed that most participants exploit music for a wide
      range of purposes in the cognitive, emotional and social domains, including mood
      management, personal development and social inclusion. However, in contrast to
      typically developing people, the ASD group's descriptions of mood states
      reflected a greater reliance on internally focused (arousal) rather than
      externally focused (emotive) language.

PMID- 19176576
TI  - Similarities and differences between children and adolescents with autism
      spectrum disorder and those with obsessive compulsive disorder: executive
      functioning and repetitive behaviour.
AB  - In order to examine hypothesized underlying neurocognitive processes in
      repetitive behaviour, children and adolescents (7-16 years) with autism spectrum
      disorder (ASD) and obsessive compulsive disorder (OCD) were compared on a range
      of executive function (EF) measures. Performance on neuropsychological tests
      assessing executive functioning showed a trend for children with ASD to perform
      poorly on tasks requiring generation of multiple responses, while children with
      OCD tended to demonstrate impairments on a task requiring inhibition. Parental
      ratings on a questionnaire measure of EF indicated impairments in both groups
      relative to controls. Relationships between questionnaire and performance
      measures of EF were generally weak. There was some limited support for a
      relationship between EF and repetitive behaviour, but effects tended to be small
      and variable across groups and measures.

PMID- 19176577
TI  - Siblings of individuals with an autism spectrum disorder: sibling relationships
      and wellbeing in adolescence and adulthood.
AB  - We investigated sibling relationships and wellbeing in adolescents and adults
      with a sibling with an autism spectrum disorder (ASD). Adolescents engaged in
      more shared activities than did adults. Adolescents reported greater social
      support, greater use of emotion-focused coping strategies, and less use of
      problem-focused coping than adults. In adulthood, females with a sister with ASD
      reported the most positive affect in the sibling relationship and men with a
      sister with ASD the least. Adolescents engaged in more shared activities and
      reported more positive affect in their sibling relationship when their sibling
      with ASD had fewer behavior problems; greater use of problem-focused coping
      buffered the negative effects of behavior problems on sibling engagement. For
      adults, more shared activities were observed when the sibling with ASD was
      younger in age and had fewer behavior problems; greater positive affect in
      sibling relationships was predicted by greater parental support.

PMID- 19176578
TI  - Quality of life of family caregivers of children with autism: The mother's
      perspective.
AB  - The purpose of this study was to explore the relationship between the quality of
      life (QOL) and feeling of mothers of a child with autism. The QOL instrument was
      also used. A total of 104 participants completed all questionnaires, which
      included the Taiwan version of the WHOQOL-BREF. A final robust parsimonious
      structural model showed a positive correlation between the four domains of QOL.
      Mother's feeling was positively related to the physical and psychological
      domains. History of chronic disease was negatively related to mother's feeling
      and the physical domain. Religion was negatively correlated with the
      psychological and environmental domains. The study provided evidence that the
      WHOQOL-BREF is an adequate and appropriate instrument in the assessment of
      caregivers of children with autism in Taiwan. Mother's feeling, history of
      chronic disease and religion were related to QOL in these mothers of children
      with autism.

PMID- 19176579
TI  - Can one hour per week of therapy lead to lasting changes in young children with
      autism?
AB  - Deficits in attention, communication, imitation, and play skills reduce
      opportunities for children with autism to learn from natural interactive
      experiences that occur throughout the day. These developmental delays are already
      present by the time these children reach the toddler period. The current study
      provided a brief 12 week, 1 hour per week, individualized parent-child education
      program to eight toddlers newly diagnosed with autism. Parents learned to
      implement naturalistic therapeutic techniques from the Early Start Denver Model,
      which fuses developmental- and relationship-based approaches with Applied
      Behavior Analysis into their ongoing family routines and parent-child play
      activities. Results demonstrated that parents acquired the strategies by the
      fifth to sixth hour and children demonstrated sustained change and growth in
      social communication behaviors. Findings are discussed in relation to providing
      parents with the necessary tools to engage, communicate with, and teach their
      young children with autism beginning immediately after the diagnosis.

PMID- 19176580
TI  - A response to the article on the association between paracetamol/acetaminophen:
      use and autism by Stephen T. Schultz.

PMID- 19176582
TI  - SoxF is part of a novel negative-feedback loop in the wingless pathway that
      controls proliferation in the Drosophila wing disc.
AB  - Wnt molecules act as mitogenic signals during the development of multiple organs,
      and the aberrant activity of their pathway is often associated with cancer.
      Therefore, the production of Wnts and the activity of their signaling pathway
      must be tightly regulated. We have investigated the mechanisms of this regulation
      in the Drosophila hinge, a domain within the wing imaginal disc that depends on
      the fly Wnt1 ortholog wingless (wg) for its proliferation. Our results uncover a
      new feedback loop in the wg pathway in which the spatially restricted activation
      of the Sox gene SoxF (Sox15) by wg represses its own transcription, thus ensuring
      tight regulation of growth control. rotund, a wing proximodistal patterning gene,
      excludes SoxF from a thin rim of cells. These cells are thus allowed to express
      wg and act as the source of mitogenic signal. This novel mode of action of a Sox
      gene on the Wnt pathway -- through transcriptional repression of a Wnt gene --
      might be relevant to human disease, as loss of human SoxF genes has been
      implicated in colon carcinoma.

PMID- 19176583
TI  - Steroids initiate a signaling cascade that triggers rapid sporulation in
      Dictyostelium.
AB  - Encapsulation of prespore cells of Dictyostelium discoideum is controlled by
      several intercellular signals to ensure appropriate timing during fruiting body
      formation. Acyl-CoA-binding protein, AcbA, is secreted by prespore cells and
      processed by the prestalk protease TagC to form the 34 amino acid peptide SDF-2
      that triggers rapid encapsulation. AcbA is secreted when gamma-aminobutyric acid
      (GABA) is released from prespore cells and binds to GrlE, a G protein-coupled
      receptor (GPCR). Analysis of SDF-2 production in mutant strains lacking Galpha
      subunits and GPCRs, either as pure populations or when mixed with other mutant
      strains, uncovered the non-cell-autonomous roles of GrlA, Galpha4 and Galpha7. We
      found that Galpha7 is essential for the response to GABA and is likely to be
      coupled to GrlE. GrlA-null and Galpha4-null cells respond normally to GABA but
      fail to secrete it. We found that they are necessary for the response to a small
      hydrophobic molecule, SDF-3, which is released late in culmination.
      Pharmacological inhibition of steroidogenesis during development blocked the
      production of SDF-3. Moreover, the response to SDF-3 could be blocked by the
      steroid antagonist mifepristone, whereas hydrocortisone and other steroids
      mimicked the effects of SDF-3 when added in the nanomolar range. It appears that
      SDF-3 is a steroid that elicits rapid release of GABA by acting through the GPCR
      GrlA, coupled to G protein containing the Galpha4 subunit. SDF-3 is at the head
      of the cascade that amplifies the signal for encapsulation to ensure the rapid,
      synchronous formation of spores.

PMID- 19176584
TI  - Intermuscular tendons are essential for the development of vertebrate stomach.
AB  - Gastrointestinal motility is ensured by the correct coordination of the enteric
      nervous system and the visceral smooth muscle cells (SMCs), and defective
      development of SMCs results in gut malformations and intestinal obstructions. In
      order to identify the molecular mechanisms that control the differentiation of
      the visceral mesenchyme into SMCs in the vertebrate stomach, we developed
      microarrays to analyze the gene expression profiles of undifferentiated and
      differentiated avian stomachs. We identify Scleraxis, a basic-helix-loop-helix
      transcription factor, as a new marker of stomach mesenchyme and find that
      expression of Scleraxis defines the presence of two tendons closely associated to
      the two visceral smooth muscles. Using targeted gene misexpression, we show that
      FGF signaling is sufficient to induce Scleraxis expression and to establish two
      tendon domains adjacent to the smooth muscle structures. We also demonstrate that
      the tendon organization is perturbed by altering Scleraxis expression or
      function. Moreover, using primary cells derived from stomach mesenchyme, we find
      that undifferentiated stomach mesenchyme can give rise to both SMCs and tendon
      cells. These data show that upon FGF activation, selected stomach mesenchymal
      cells are primed to express Scleraxis and to differentiate into tendon cells. Our
      findings identify a new anatomical and functional domain in the vertebrate
      stomach that we characterize as being two intermuscular tendons closely
      associated with the visceral SMC structures. We also demonstrate that the
      coordinated development of both tendon and smooth muscle domains is essential for
      the correct morphogenesis of the stomach.

PMID- 19176585
TI  - Differential requirements of BMP and Wnt signalling during gastrulation and
      neurulation define two steps in neural crest induction.
AB  - The neural crest is induced by a combination of secreted signals. Although
      previous models of neural crest induction have proposed a step-wise activation of
      these signals, the actual spatial and temporal requirement has not been analysed.
      Through analysing the role of the mesoderm we show for the first time that
      specification of neural crest requires two temporally and chemically different
      steps: first, an induction at the gastrula stage dependent on signals arising
      from the dorsolateral mesoderm; and second, a maintenance step at the neurula
      stage dependent on signals from tissues adjacent to the neural crest. By
      performing tissue recombination experiments and using specific inhibitors of
      different inductive signals, we show that the first inductive step requires Wnt
      activation and BMP inhibition, whereas the later maintenance step requires
      activation of both pathways. This change in BMP necessity from BMP inhibition at
      gastrula to BMP activation at neurula stages is further supported by the dynamic
      expression of BMP4 and its antagonists, and is confirmed by direct measurements
      of BMP activity in the neural crest cells. The differential requirements of BMP
      activity allow us to propose an explanation for apparently discrepant results
      between chick and frog experiments. The demonstration that Wnt signals are
      required for neural crest induction by mesoderm solves an additional long
      standing controversy. Finally, our results emphasise the importance of
      considering the order of exposure to signals during an inductive event.

PMID- 19176586
TI  - Neurovascular development uses VEGF-A signaling to regulate blood vessel
      ingression into the neural tube.
AB  - Neurovascular development requires communication between two developing organs,
      the neuroepithelium and embryonic blood vessels. We investigated the role of VEGF
      A signaling in the embryonic crosstalk required for ingression of angiogenic
      vessel sprouts into the developing neural tube. As the neural tube develops,
      blood vessels enter at specific points medially and ventrally from the
      surrounding perineural vascular plexus. Localized ectopic expression of heparin
      binding VEGF165 or VEGF189 from the developing avian neural tube resulted in
      supernumerary blood vessel ingression points and disrupted vessel patterning. By
      contrast, localized ectopic neural expression of non-heparin-binding VEGF121 did
      not produce supernumerary blood vessel ingression points, although the vessels
      that entered the neural tube became dysmorphogenic. Localized loss of endogenous
      VEGF-A signaling in the developing neural tube via ectopic expression of the VEGF
      inhibitor sFlt-1 locally blocked blood vessel ingression. The VEGF pathway
      manipulations were temporally controlled and did not dramatically affect neural
      tube maturation and dorsal-ventral patterning. Thus, neural-derived VEGF-A has a
      direct role in the spatially localized molecular crosstalk that is required for
      neurovascular development and vessel patterning in the developing neural tube.

PMID- 19176587
TI  - Tcf3 inhibits spinal cord neurogenesis by regulating sox4a expression.
AB  - The Lef/Tcf factor Tcf3 is expressed throughout the developing vertebrate central
      nervous system (CNS), but its function and transcriptional targets are
      uncharacterized. Tcf3 is thought to mediate canonical Wnt signaling, which
      functions in CNS patterning, proliferation and neurogenesis. In this study, we
      examine Tcf3 function in the zebrafish spinal cord, and find that this factor
      does not play a general role in patterning, but is required for the proper
      expression of Dbx genes in intermediate progenitors. In addition, we show that
      Tcf3 is required to inhibit premature neurogenesis in spinal progenitors by
      repressing sox4a, a known mediator of spinal neurogenesis. Both of these
      functions are mediated by Tcf3 independently of canonical Wnt signaling.
      Together, our data indicate a novel mechanism for the regulation of neurogenesis
      by Tcf3-mediated repression.

PMID- 19176588
TI  - Coordinate integrin and c-Met signaling regulate Wnt gene expression during
      epithelial morphogenesis.
AB  - Integrin receptors for the extracellular matrix and receptor tyrosine kinase
      growth factor receptors represent two of the major families of receptors that
      transduce into cells information about the surrounding environment. Wnt proteins
      are a major family of signaling molecules that regulate morphogenetic events.
      There is presently little understanding of how the expression of Wnt genes
      themselves is regulated. In this study, we demonstrate that alpha3beta1 integrin,
      a major laminin receptor involved in the development of the kidney, and c-Met,
      the receptor for hepatocyte growth factor, signal coordinately to regulate the
      expression of Wnt7b in the mouse. Wnt signals in turn appear to regulate
      epithelial cell survival in the papilla of the developing kidney, allowing for
      the elongation of epithelial tubules to form a mature papilla. Together, these
      results demonstrate how signals from integrins and growth factor receptors can be
      integrated to regulate the expression of an important family of signaling
      molecules so as to regulate morphogenetic events.

PMID- 19176589
TI  - The NAC-domain transcription factor GOBLET specifies leaflet boundaries in
      compound tomato leaves.
AB  - Leaves are formed at the flanks of the shoot apical meristem (SAM) and develop
      into a variety of forms. In tomato, prolonged leaf patterning enables the
      elaboration of compound leaves by reiterative initiation of leaflets with lobed
      margins. In goblet (gob) loss-of-function mutants, primary leaflets are often
      fused, secondary leaflets and marginal serrations are absent, and SAMs often
      terminate precociously. We show that GOB encodes a NAC-domain transcription
      factor expressed in narrow stripes at the leaf margins, flanking the distal side
      of future leaflet primordia, and at the boundaries between the SAM and leaf
      primordia. Leaf-specific overexpression of the microRNA miR164, a negative
      regulator of GOB-like genes, also leads to loss of secondary-leaflet initiation
      and to smooth leaflet margins. Plants carrying a dominant gob allele with an
      intact ORF but disrupted miR164 binding site produce more cotyledons and floral
      organs, have split SAMs and, surprisingly, simpler leaves. Overexpression of a
      form of GOB with an altered miR164 binding site in leaf primordia leads to
      delayed leaflet maturation, frequent, improperly timed and spaced initiation
      events, and a simple mature leaflet form owing to secondary-leaflet fusion.
      miR164 also affects leaflet separation in Cardamine hirsuta, a Brassicaceae
      species with complex leaves. Genetic and molecular analyses suggest that GOB
      expression is intact in the simplified leaves of entire tomato mutants, which
      have a defect in a putative repressor of auxin responses. Our results show that
      GOB marks leaflet boundaries and that its accurate spatial, temporal and
      quantitative activity affects leaf elaboration in a context-dependent manner.

PMID- 19176590
TI  - Regulation of the Rac GTPase pathway by the multifunctional Rho GEF Pebble is
      essential for mesoderm migration in the Drosophila gastrula.
AB  - The Drosophila guanine nucleotide exchange factor Pebble (Pbl) is essential for
      cytokinesis and cell migration during gastrulation. In dividing cells, Pbl
      promotes Rho1 activation at the cell cortex, leading to formation of the
      contractile actin-myosin ring. The role of Pbl in fibroblast growth factor
      triggered mesoderm spreading during gastrulation is less well understood and its
      targets and subcellular localization are unknown. To address these issues we
      performed a domain-function study in the embryo. We show that Pbl is localized to
      the nucleus and the cell cortex in migrating mesoderm cells and found that, in
      addition to the PH domain, the conserved C-terminal tail of the protein is
      crucial for cortical localization. Moreover, we show that the Rac pathway plays
      an essential role during mesoderm migration. Genetic and biochemical interactions
      indicate that during mesoderm migration, Pbl functions by activating a Rac
      dependent pathway. Furthermore, gain-of-function and rescue experiments suggest
      an important regulatory role of the C-terminal tail of Pbl for the selective
      activation of Rho1-versus Rac-dependent pathways.

PMID- 19176591
TI  - Altered sterol profile induced in Leishmania amazonensis by a natural
      dihydroxymethoxylated chalcone.
AB  - OBJECTIVES: The effects of the antileishmanial chalcone 2',6'-dihydroxy-4'
      methoxychalcone (DMC) on Leishmania amazonensis sterol composition and
      biosynthesis were investigated to obtain information about the mechanism of
      growth inhibition by DMC on this parasite. METHODS: The interference of sterol
      biosynthesis by DMC was studied in drug-treated promastigotes by two different
      methods. (i) Newly synthesized sterols from parasites grown in the presence of
      [(3)H]mevalonate were analysed by thin layer chromatography (TLC)/fluorography.
      (ii) Total sterols extracted from the parasites grown with or without DMC were
      characterized by gas chromatography coupled to mass spectroscopy (GC/MS).
      RESULTS: TLC and GC/MS analyses of sterols extracted from DMC-treated
      promastigotes revealed the accumulation of early precursors and a reduction in
      the levels of C-14 demethylated and C-24 alkylated sterols, as well as a
      reduction in exogenous cholesterol uptake. CONCLUSIONS: This study demonstrates
      that the natural chalcone DMC alters the sterol composition of L. amazonensis and
      suggests that the parasite target is different from other known sterol
      inhibitors.

PMID- 19176592
TI  - Mitochondria and human preimplantation embryo development.
AB  - Human reproduction, like all biological systems, is characterised by a large
      level of variability. In this field, the variability is observed as a large
      difference in implantation potential of human embryos developing in vitro,
      despite similarities in observable parameters such as rate of development and
      morphology of these embryos. One of the underlying factors that determines
      developmental potential in these embryos is the availability of energy in the
      form of ATP for development. Here, we suggest that, despite the evidence
      suggesting that mitochondrial metabolism is relatively inactive during
      preimplantation embryo development, aerobic (mitochondrial) metabolism
      contributes a major role in the supply of ATP. A second pathway, anaerobic
      respiration, is also active and the two pathways work in synchrony to supply all
      the ATP necessary. We discuss the differences in the two forms of energy
      production and suggest that, although anaerobic respiration can supplement
      deficiencies in the energy supply in the short term, this is not sufficient to
      substitute for aerobic respiration over long periods. Therefore, we suggest that
      deficiencies in the levels of aerobic respiration can explain variability in the
      implantation potential of apparently equivalent embryos.

PMID- 19176593
TI  - Sintered indium-tin-oxide (ITO) particles: a new pneumotoxic entity.
AB  - Indium-Tin-Oxide (ITO) is a sintered mixture of indium- (In(2)O(3)) and tin-oxide
      (SnO(2)) in a ratio of 90:10 (wt:wt) that is used for the manufacture of LCD
      screens and related high technology applications. Interstitial pulmonary diseases
      have recently been reported in workers from ITO producing plants. The present
      study was conducted to identify experimentally the exact chemical component
      responsible for this toxicity and to address possible mechanisms of action. The
      reactivity of respirable ITO particles was compared with that of its single
      components alone or their unsintered 90:10 mixture (MIX) both in vivo and in
      vitro. For all endpoints considered, ITO particles behaved as a specific toxic
      entity. In vivo, after a single pharyngeal administration (2-20 mg per rat), ITO
      particles induced a strong inflammatory reaction. At day 3, the inflammatory
      reaction (cell accumulation, LDH and protein in bronchoalveolar lavage fluid)
      appeared more marked with ITO particles than with each oxide separately or the
      MIX. This inflammatory reaction persisted and even worsened after 15 days. After
      60 days, this inflammation was still present but no significant fibrotic response
      was observed. The cytotoxicity of ITO was assessed in vitro in lung epithelial
      cells (RLE) and macrophages (NR8383 cell line). While ITO particles (up to 200
      microg/ml) did not affect epithelial cell integrity (LDH release), a strong
      cytotoxic response was found in macrophages exposed to ITO, but not to its
      components alone or mixed. ITO particles also induced an increased frequency of
      micronuclei in type II pneumocytes in vivo but not in RLE in vitro, suggesting
      the preponderance of a secondary genotoxic mechanism. To address the possible
      mechanism of ITO toxicity, reactive oxygen species production was assessed by
      electron paramagnetic resonance spectrometry in an acellular system. Carbon
      centered radicals (COO-.) and Fenton-like activity were detected in the presence
      of ITO particles, not with In(2)O(3), SnO(2) alone, or the MIX. Because the
      unsintered mixture of SnO(2) and In(2)O(3) particles was unable to reproduce the
      reactivity/toxicity of ITO particles, the sintering process through which SnO(2)
      molecules are introduced within the crystal structure of In(2)O(3) appears
      critical to explain the unique toxicological properties of ITO. The inflammatory
      and genotoxic activities of ITO dust indicate that a strict control of exposure
      is needed in industrial settings.

PMID- 19176594
TI  - N-acetyl cysteine mediates protection from 2-hydroxyethyl methacrylate induced
      apoptosis via nuclear factor kappa B-dependent and independent pathways:
      potential involvement of JNK.
AB  - The mechanisms by which resin based materials induce adverse effects in patients
      have not been completely elucidated. Here we show that 2-hydroxyethyl
      methacrylate (HEMA) induces apoptotic cell death in oral keratinocytes.
      Functional loss and cell death induced by HEMA was significantly inhibited in the
      presence of N-acetyl cysteine (NAC) treatment. NAC also prevented HEMA mediated
      decrease in vascular endothelial growth factor secretion. The protective effect
      of NAC was partly related to its ability to induce NF-kappaB in the cells, since
      HEMA mediated inhibition of nuclear NF-kappaB expression and function was
      significantly blocked in the presence of NAC treatment. Moreover, blocking of
      nuclear translocation of NF-kappaB in oral keratinocytes sensitized these cells
      to HEMA mediated apoptosis. In addition, since NAC was capable of rescuing close
      to 50% of NF-kappaB knockdown cells from HEMA mediated cell death, there is,
      therefore, an NF-kappaB independent pathway of protection from HEMA mediated cell
      death by NAC. NAC mediated prevention of HEMA induced cell death in NF-kappaB
      knockdown cells was correlated with a decreased induction of c-Jun N-terminal
      kinase (JNK) activity since NAC inhibited HEMA mediated increase in JNK levels.
      Furthermore, the addition of a pharmacologic JNK inhibitor to HEMA treated cells
      prevented cell death and restored NF-kappaB knockdown cell function
      significantly. Therefore, NAC protects oral keratinocytes from the toxic effects
      of HEMA through NF-kappaB dependent and independent pathways. Moreover, our data
      suggest the potential involvement of JNK pathway in NAC mediated protection.

PMID- 19176595
TI  - Directed evolution of homing endonuclease I-SceI with altered sequence
      specificity.
AB  - Homing endonucleases recognize specific long DNA sequences and catalyze double
      stranded breaks that significantly stimulate homologous recombination,
      representing an attractive tool for genome targeting and editing. We previously
      described a two-plasmid selection system that couples enzymatic DNA cleavage with
      the survival of host cells, and enables directed evolution of homing
      endonucleases with altered cleavage sequence specificity. Using this selection
      system, we successfully evolved mutant I-SceI homing endonucleases with greatly
      increased cleavage activity towards a new target DNA sequence that differs from
      the wild-type cleavage sequence by 4 bp. The most highly evolved mutant showed a
      survival rate approximately 100-fold higher than that of wild-type I-SceI enzyme.
      The degree of selectivity displayed by a mutant isolated from one round of
      saturation mutagenesis for the new target sequence is comparable to that of wild
      type I-SceI for the natural sequence. These results highlight the ability and
      efficiency of our selection system for engineering homing endonucleases with
      novel DNA cleavage specificities. The mutant identified from this study can
      potentially be used in vivo for targeting the new cleavage sequence within
      genomic DNA.

PMID- 19176596
TI  - Cardioprotection by hypoxia-inducible factor 1 alpha transfection in skeletal
      muscle is dependent on haem oxygenase activity in mice.
AB  - AIMS: The present study investigates whether the cardioprotection achieved by
      gene delivery of hypoxia-inducible factor-1 alpha (HIF-1 alpha) depends on the
      downstream factor haem oxygenase (HMOX)-1. METHODS AND RESULTS: Immortalized
      cardiomyocytes (HL-1 cells) were transfected with HIF-1 alpha or HMOX-1 and
      injured with hydrogen peroxide (H(2)O(2)), and death was evaluated by trypan blue
      staining. Quadriceps muscles of mice were treated with DNA for HIF-1 alpha and
      HMOX-1, or sham-treated and electroporated, and 3 days later, hearts were
      isolated and subjected to global ischaemia and reperfusion. Some HIF-1 alpha- and
      sham-treated mice received the HMOX blocker zinc deuteroporphyrin 2,4-bis-glycol
      (ZnBG) (n = 6-8 in each group). HL-1 cells were stimulated with bilirubin or the
      carbon monoxide donor CORM-2 before injury with H(2)O(2). HL-1 cells which were
      transfected with HIF-1 alpha or HMOX-1 had an increased survival to H(2)O(2)
      induced injury compared with empty vector (n = 10-12 per group; P < 0.01 for
      both). When HMOX-1-luciferase reporter mice were treated with HIF-1 alpha in the
      quadriceps muscle, increased luciferase activity was found locally, but nowhere
      else. Mice pre-treated with HIF-1 alpha or HMOX-1 had a reduced infarct size,
      improved post-ischaemic function, and increased serum bilirubin (P < 0.05). ZnBG
      inhibited all these effects afforded by HIF-1 alpha. Stimulation of HL-1 cells
      with bilirubin and CORM-2 reduced cell death evoked by H(2)O(2) (P < 0.05 for
      both, n = 11-15 in each group). CONCLUSION: HIF-1 alpha and HMOX-1 provided
      protection against H(2)O(2)-induced damage in HL-1 cells. Remote gene delivery of
      HIF-1 alpha afforded cardioprotective effects. These were dependent on HMOX
      activity, as an HMOX blocker abolished the effects, and they were mimicked by pre
      treatment with HMOX-1. Downstream to HMOX-1, bilirubin as well as carbon monoxide
      may be organ effectors.

PMID- 19176597
TI  - RAGE mediates oxidized LDL-induced pro-inflammatory effects and atherosclerosis
      in non-diabetic LDL receptor-deficient mice.
AB  - AIMS: Receptor for advanced glycation end products (RAGE) plays a pivotal role in
      the genesis of diabetic vascular diseases. To further explore the mechanisms
      underlying atherosclerosis under non-diabetic conditions, we examined the effect
      of RAGE deficiency on atherosclerosis in hyperlipidaemic mice. METHODS AND
      RESULTS: RAGE-/- mice were crossed with low-density lipoprotein receptor
      deficient (LDLr-/-) mice to generate the double knockout (DKO) mice. After
      feeding with high-fat diet for 12 weeks, aortic atherosclerotic lesions were
      analysed histologically in these mice. Although there were no differences in
      serum levels of glucose and known RAGE ligands between DKO and LDLr-/- mice, DKO
      mice exhibited a significant decrease in the size and macrophage content in
      atherosclerotic lesions compared with LDLr-/- mice. Expression of intracellular
      adhesion molecule-1 and vascular cell adhesion molecule-1 in the aorta was lower
      in DKO mice than in LDLr-/- mice. Fluorescence-based assays revealed that
      oxidative stress in the vessel wall was attenuated in DKO mice than in LDLr-/-
      mice. Cell culture experiments revealed that RAGE mediated oxidative LDL-induced
      activation of p42/44 mitogen-activated protein kinases and oxidative stress in
      macrophages. CONCLUSION: Oxidative LDL may be a ligand of RAGE in the
      hyperlipidaemic state. RAGE inactivation inhibits the atherosclerosis through
      reducing oxLDL-induced pro-inflammatory responses and oxidative stress in
      hyperlipidaemia.

PMID- 19176598
TI  - Human cardiac gap-junction coupling: effects of antiarrhythmic peptide AAP10.
AB  - AIMS: Ventricular arrhythmia is one of the most important causes of death in
      industrialized countries and often accompanies myocardial infarction and heart
      failure. In recent years modification of gap-junctional coupling has been
      proposed as a new antiarrhythmic principle. We wanted to examine whether the gap
      junction modulator (antiarrhythmic peptide) AAP10 exerts effects on human cardiac
      gap junctions, whether the effect might be enhanced in uncoupled cells, whether
      it affects electrical and metabolic coupling, and which of the cardiac connexin
      isoforms (Cx40, Cx43, Cx45) may be affected. METHODS AND RESULTS: We determined
      the influence of 50 nM AAP10 (H(2)N-Gly-Ala-Gly-4Hyp-Pro-Tyr-CONH(2)) on
      macroscopic gap junction conductance by dual whole-cell voltage clamping in human
      and rat cardiomyocytes. Cells were partially uncoupled by CO(2)-mediated acidosis
      (pH 6.3) or kept at 'normal' conditions (pH 7.4, T 36 degrees C). Furthermore, we
      investigated effects of AAP10 in HeLa cells stably transfected with connexin 40,
      43, or 45 and on metabolic coupling determined by dye transfer (Lucifer yellow).
      AAP10 (50 nM)-enhanced gap-junctional intercellular coupling in human and rat
      cardiomyocytes, completely prevented CO(2)-acidosis-induced uncoupling and
      improved metabolic coupling. The coupling effect of AAP10 was significantly
      enhanced in previously uncoupled cells. Regarding the connexin isoforms, AAP10
      enhanced electrical and metabolic coupling in HeLa cells expressing Cx43 or Cx45,
      but not in HeLa cells expressing Cx40. CONCLUSION: We conclude that the
      antiarrhythmic peptide AAP10, which improves gap-junctional intercellular
      coupling and prevents uncoupling by acidification in human cardiomyocytes, might
      be useful for antiarrhythmic strategies regarding arrhythmias caused by
      uncoupling of Cx43 and Cx45, but not Cx40.

PMID- 19176599
TI  - Structural and functional cardiac cholinergic deficits in adult neurturin
      knockout mice.
AB  - AIMS: Previous work provided indirect evidence that the neurotrophic factor
      neurturin (NRTN) is required for normal cholinergic innervation of the heart.
      This study used nrtn knockout (KO) and wild-type (WT) mice to determine the
      effect of nrtn deletion on cardiac cholinergic innervation and function in the
      adult heart. METHODS AND RESULTS: Immunohistochemistry, confocal microscopy, and
      quantitative image analysis were used to directly evaluate intrinsic cardiac
      neuronal development. Atrial acetylcholine (ACh) levels were determined as an
      indirect index of cholinergic innervation. Cholinergic function was evaluated by
      measuring negative chronotropic responses to right vagal nerve stimulation in
      anaesthetized mice and responses of isolated atria to muscarinic agonists. KO
      hearts contained only 35% the normal number of cholinergic neurons, and the
      residual cholinergic neurons were 15% smaller than in WT. Cholinergic nerve
      density at the sinoatrial node was reduced by 87% in KOs, but noradrenergic nerve
      density was unaffected. Atrial ACh levels were substantially lower in KO mice
      (0.013 +/- 0.004 vs. 0.050 +/- 0.011 pmol/microg protein; P < 0.02) as expected
      from cholinergic neuron and nerve fibre deficits. Maximum bradycardia evoked by
      vagal stimulation was reduced in KO mice (38 +/- 6% vs. 69 +/- 3% decrease at 20
      Hz; P < 0.001), and chronotropic responses took longer to develop and fade. In
      contrast to these deficits, isolated atria from KO mice had normal post
      junctional sensitivity to carbachol and bethanechol. CONCLUSION: These findings
      demonstrate that NRTN is essential for normal cardiac cholinergic innervation and
      cholinergic control of heart rate. The presence of residual cardiac cholinergic
      neurons and vagal bradycardia in KO mice suggests that additional neurotrophic
      factors may influence this system.

PMID- 19176600
TI  - Benefits of reperfusion beyond infarct size limitation.
AB  - The most critical determinant of prognosis in patients with acute myocardial
      infarction (MI) is infarct magnitude, which can be established within several
      hours of an attack. The importance of the subsequent healing process is not
      negligible, however. In fact, much experimental and clinical evidence suggests
      that late reperfusion of the infarct-related coronary artery--i.e. at times too
      late to salvage the myocardium within the area at risk-is beneficial for reducing
      left ventricular remodelling and decreasing mortality ('open artery hypothesis').
      For instance, one recent study highlighted the beneficial effects of late
      reperfusion therapy on the infarct tissue cell dynamics following acute MI.
      Nonetheless, several recent large, randomized clinical trials have failed to
      provide evidence of such benefits, refuting the clinical efficacy of late
      reperfusion. In addition, they also underscore the need for revised clinical
      studies in which there is less heterogeneity in the timing of reperfusion and in
      the initial infarct size, as well as the need for sustained patency of the
      recanalized artery. This review focuses on the effects of late reperfusion on the
      pathophysiology of MI in the context of the infarct tissue dynamics and clinical
      outcomes. We also discuss the issues that need to be resolved to improve clinical
      application.

PMID- 19176601
TI  - Loss of cardioprotection with ageing.
AB  - Not only the prevalence, but also the mortality due to ischaemic cardiovascular
      disease is higher in older than in young humans, and the demographic shift
      towards an ageing population will further increase the prevalence of age-related
      cardiovascular disease. In order to develop strategies aimed to limit reversible
      and irreversible myocardial damage in older patients, there is a need to better
      understand age-induced alterations in protein expression and cell signalling.
      Cardioprotective phenomena such as ischaemic and pharmacological pre and
      postconditioning attenuate ischaemia/reperfusion injury in young hearts. Whether
      or not pre and postconditioning are still effective in aged organs, animals, or
      patients, i.e. under conditions where such cardioprotection is most relevant, is
      still a matter of debate; most studies suggest a loss of protection in aged
      hearts. The present review discusses changes in protein expression and cell
      signalling important to ischaemia/reperfusion injury with myocardial ageing. The
      efficacy of cardioprotective manoeuvres, e.g. ischaemic pre and postconditioning
      in aged organs and animals will be discussed, and the development of strategies
      aimed to antagonize the age-induced loss of protection will be addressed.

PMID- 19176602
TI  - Effect of uncoupling endothelial nitric oxide synthase on calcium homeostasis in
      aged porcine endothelial cells.
AB  - AIMS: The requirement of endothelial NO synthase (NOS3) calcium to produce NO is
      well described, although the effect of NO on intracellular calcium levels
      [Ca(2+)](i) is still confusing. Therefore, NO and [Ca(2+)](i) cross-talk were
      studied in parallel in endothelial cells possessing a functional or a
      dysfunctional NO pathway. METHODS AND RESULTS: Dysfunctional porcine endothelial
      cells were obtained either in vitro by successive passages or in vivo from
      regenerated endothelium 1 month after coronary angioplasty. Activity of NOS3 was
      characterized by conversion of arginine to citrulline, BH(4) intracellular
      availability, cGMP, and superoxide anion production. Imaging of the Ca(2+)
      indicator FURA 2-AM was recorded and sarco/endoplasmic reticulum Ca(2+) ATPase
      (SERCA) pump activity was analysed by (45)Ca(2+) uptake into cells. In
      endothelial cells with a functional NO pathway, NOS3 inhibition increased
      [Ca(2+)](i) and, conversely, an NO donor decreased it. In aged cells with an
      uncoupled NOS3 as shown by the reduced BH(4) level, the increase in superoxide
      anion and the lower production of cGMP and the decrease in NO bioavailability
      were linearly correlated with the increase in basal [Ca(2+)](i). Moreover, when
      stimulated by bradykinin, the calcium response was reduced while its decay was
      slowed down. These effects on the calcium signalling were abolished in calcium
      free buffer and were similarly induced by SERCA inhibitors. In aged cells, NO
      improved the reduced SERCA activity and tended to normalize the agonist calcium
      response. CONCLUSION: In control endothelial cells, NO exerts a negative feedback
      on cytosolic Ca(2+) homeostasis. In aged cells, uncoupled NOS3 produced NO that
      was insufficient to control the [Ca(2+)](i). Consequently, under resting
      conditions, SERCA activity decreased and [Ca(2+)](i) increased. These alterations
      were reversible as exogenous NO, in a cGMP-independent way, refilled
      intracellular calcium stores, reduced calcium influx, and improved the agonist
      evoked calcium response. Therefore, prevention of the decrease in NO in
      dysfunctional endothelium would normalize the calcium-dependent functions.

PMID- 19176603
TI  - Sphingomyelinases: their regulation and roles in cardiovascular pathophysiology.
AB  - Sphingomyelinases (SMases) hydrolyse sphingomyelin, releasing ceramide and
      creating a cascade of bioactive lipids. These lipids include sphingosine and
      sphingosine-1-phosphate, all of which have a specific signalling capacity.
      Sphingomyelinase activation occurs in different cardiovascular system cell types,
      namely cardiac myocytes, endothelial and vascular smooth muscle cells, mediating
      cell proliferation, cell death, and contraction of cardiac and vascular myocytes.
      Three main types of SMases contribute to cardiovascular physiology: the lysosomal
      and secreted acidic SMases (L- and S-ASMases, respectively) and the membrane
      neutral SMase (NSMase). These three enzymes have common activators, including
      ischaemia/reperfusion stress and proinflammatory cytokines, but they differ in
      their enzymatic properties and subcellular locations that determine the final
      effect of enzyme activation. This review focuses on the recent advances in the
      understanding of ASMase and NSMase pathways and their specific contribution to
      cardiovascular pathophysiology. Current knowledge indicates that the inhibitors
      of the different SMase types are potential tools for the treatment of
      cardiovascular diseases. Acid SMase inhibitors could be tools against post
      ischaemia reperfusion injury and in the treatment of atherosclerosis. Neutral
      SMase inhibitors could be tools for the treatment of atherosclerosis, heart
      failure, and age-related decline in vasomotion. However, the design of
      bioavailable and more specific SMase-type inhibitors remains a challenge.

PMID- 19176604
TI  - Impact of normalization on miRNA microarray expression profiling.
AB  - Profiling miRNA levels in cells with miRNA microarrays is becoming a widely used
      technique. Although normalization methods for mRNA gene expression arrays are
      well established, miRNA array normalization has so far not been investigated in
      detail. In this study we investigate the impact of normalization on data
      generated with the Agilent miRNA array platform. We have developed a method to
      select nonchanging miRNAs (invariants) and use them to compute linear regression
      normalization coefficients or variance stabilizing normalization (VSN)
      parameters. We compared the invariants normalization to normalization by scaling,
      quantile, and VSN with default parameters as well as to no normalization using
      samples with strong differential expression of miRNAs (heart-brain comparison)
      and samples where only a few miRNAs are affected (by p53 overexpression in
      squamous carcinoma cells versus control). All normalization methods performed
      better than no normalization. Normalization procedures based on the set of
      invariants and quantile were the most robust over all experimental conditions
      tested. Our method of invariant selection and normalization is not limited to
      Agilent miRNA arrays and can be applied to other data sets including those from
      one color miRNA microarray platforms, focused gene expression arrays, and gene
      expression analysis using quantitative PCR.

PMID- 19176605
TI  - Distinct roles of metabotropic glutamate receptor activation on inhibitory
      signaling in the ventral lateral geniculate nucleus.
AB  - The ventral lateral geniculate nucleus (vLGN) has been implicated in numerous
      functions including circadian rhythms, brightness discrimination, pupillary light
      reflex, and other visuomotor functions. The contribution of inhibitory mechanisms
      in the regulation of vLGN neuron excitability remains unexplored. We examined the
      actions of metabotropic glutamate receptor (mGluR) activation on the intrinsic
      excitability and inhibitory synaptic transmission in different lamina of vLGN.
      Activation of mGluRs exerts distinct pre- and postsynaptic actions in vLGN
      neurons. In the lateral magnocellular subdivision of vLGN (vLGNl), the general
      mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) enhanced
      the frequency of GABA(A) receptor-mediated spontaneous inhibitory postsynaptic
      currents (sIPSC) that persisted in the presence of sodium channel blocker
      tetrodotoxin (TTX) in a subpopulation of neurons (TTX insensitive). This increase
      is attributed to the increased output of dendritic GABA release from vLGN
      interneurons. In contrast, in the medial subdivision of vLGN (vLGNm), the mGluR
      agonist-mediated increase in sIPSC frequency was completely blocked by TTX. The
      selective Group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) increased
      sIPSC frequency, whereas the selective Group II mGluR agonist (2R, 4R)-4
      aminopyrrolidine-2,4-dicarboxylate (APDC) significantly decreased sIPSC frequency
      in vLGNl neurons. Optic tract stimulation also produced an mGluR-dependent
      increase in sIPSC frequency in vLGNl neurons. In contrast, we were unable to
      synaptically evoke alterations in sIPSC activity in vLGNm neurons. In addition to
      these presynaptic actions, DHPG depolarized both vLGNl and vLGNm neurons. In vLGN
      interneurons, mGluR activation produced opposing actions: APDC hyperpolarized the
      membrane potential, whereas DHPG produced a membrane depolarization. The present
      findings demonstrate diverse actions of mGluRs on vLGN neurons localized within
      different vLGN lamina. Considering these different lamina are coupled with
      distinct functional roles, thus these diverse actions may be involved in
      distinctive forms of visual and visuomotor information processing.

PMID- 19176606
TI  - Functional consequences of neuronal divergence within the retinogeniculate
      pathway.
AB  - The neuronal connections from the retina to the dorsal lateral geniculate nucleus
      (dLGN) are characterized by a high specificity. Each retinal ganglion cell
      diverges to connect to a small group of geniculate cells and each geniculate cell
      receives input from a small number of retinal ganglion cells. Consistent with the
      high specificity of the connections, geniculate cells sharing input from the same
      retinal afferent are thought to have very similar receptive fields. However, the
      magnitude of the receptive-field mismatches, which has not been systematically
      measured across the different cell types in dLGN, seems to be in contradiction
      with the functional anatomy of the Y visual pathway: Y retinal afferents in the
      cat diverge into two geniculate layers (A and C) that have Y geniculate cells
      (Y(A) and Y(C)) with different receptive-field sizes, response latencies,
      nonlinearity of spatial summation, and contrast sensitivity. To better understand
      the functional consequences of retinogeniculate divergence, we recorded from
      pairs of geniculate cells that shared input from a common retinal afferent across
      layers and within the same layer in dLGN. We found that nearly all cell pairs
      that shared retinal input across layers had Y-type receptive fields of the same
      sign (i.e., both on-center) that overlapped by >70%, but frequently differed in
      size and response latency. The receptive-field mismatches were relatively small
      in value (receptive-field size ratio <5; difference in peak response <5 ms), but
      were robustly correlated with the strength of the synchronous firing generated by
      the shared retinal connections (R(2) = 0.75). On average, the percentage of
      geniculate spikes that could be attributed to shared retinal inputs was about 10%
      for all cell-pair combinations studied. These results are used to provide new
      estimates of retinogeniculate divergence for different cell classes.

PMID- 19176607
TI  - Neural basis of the set-size effect in frontal eye field: timing of attention
      during visual search.
AB  - Visual search for a target object among distractors often takes longer when more
      distractors are present. To understand the neural basis of this capacity
      limitation, we recorded activity from visually responsive neurons in the frontal
      eye field (FEF) of macaque monkeys searching for a target among distractors
      defined by form (randomly oriented T or L). To test the hypothesis that the delay
      of response time with increasing number of distractors originates in the delay of
      attention allocation by FEF neurons, we manipulated the number of distractors
      presented with the search target. When monkeys were presented with more
      distractors, visual target selection was delayed and neuronal activity was
      reduced in proportion to longer response time. These findings indicate that the
      time taken by FEF neurons to select the target contributes to the variation in
      visual search efficiency.

PMID- 19176608
TI  - Adaptation to visuomotor rotation and force field perturbation is correlated to
      different brain areas in patients with cerebellar degeneration.
AB  - Although it is widely agreed that the cerebellum is necessary for learning and
      consolidation of new motor tasks, it is not known whether adaptation to kinematic
      and dynamic errors is processed by the same cerebellar areas or whether different
      parts play a decisive role. We investigated arm movements in a visuomotor (VM)
      rotation and a force field (FF) perturbation task in 14 participants with
      cerebellar degeneration and 14 age- and gender-matched controls. Magnetic
      resonance images were used to calculate the volume of cerebellar areas (medial,
      intermediate, and lateral zones of the anterior and posterior lobes) and to
      identify cerebellar structure important for the two tasks. Corroborating previous
      studies, cerebellar participants showed deficits in adaptation to both tasks
      compared with controls (P < 0.001). However, it was not possible to draw
      conclusions from the performance in one task on the performance in the other task
      because an individual participant could show severe impairment in one task and
      perform relatively well in the other (rho = 0.1; P = 0.73). We found that atrophy
      of distinct cerebellar areas correlated with impairment in different tasks.
      Whereas atrophy of the intermediate and lateral zone of the anterior lobe
      correlated with impairment in the FF task (rho = 0.72, 0.70; P = 0.003, 0.005,
      respectively), atrophy of the intermediate zone of the posterior lobe correlated
      with adaptation deficits in the VM task (rho = 0.64; P = 0.015). Our results
      suggest that adaptation to the different tasks is processed independently and
      relies on different cerebellar structures.

PMID- 19176609
TI  - Time course of attentional modulation in the frontal eye field during curve
      tracing.
AB  - Neurons in the frontal eye fields (FEFs) register incoming visual information and
      select visual stimuli that are relevant for behavior. Here we investigated the
      timing of the visual response and the timing of selection by recording from
      single FEF neurons in a curve-tracing task that requires shifts of attention
      followed by an oculomotor response. We found that the behavioral selection signal
      in area FEF had a latency of 147 ms and that it was delayed substantially
      relative to the visual response, which occurred 50 ms after stimulus
      presentation. We compared the FEF responses to activity previously recorded in
      the primary visual cortex (area V1) during the same task. Visual responses in
      area V1 preceded the FEF responses, but the latencies of selection signals in
      areas V1 and FEF were similar. The similarity of timing of selection signals in
      structures at opposite ends of the visual cortical processing hierarchy supports
      the view that stimulus selection occurs in an interaction between widely
      separated cortical regions.

PMID- 19176610
TI  - Cortically activated interneurons shape spatial aspects of cortico-accumbens
      processing.
AB  - Basal ganglia circuits are organized as parallel loops that have been proposed to
      compete in a winner-take-all fashion to determine the appropriate behavioral
      outcome. However, limited experimental support for strong lateral inhibition
      mechanisms within striatal regions questions this model. Here, stimulation of the
      prefrontal cortex (PFC) using naturally occurring bursty patterns inhibited
      firing in most nucleus accumbens (NA) projection neurons. When an excitatory
      response was observed for one stimulation site, neighboring PFC sites evoked
      inhibition in the same neuron. Furthermore, PFC stimulation activated
      interneurons, and PFC-evoked inhibition was blocked by GABA(A) antagonists in
      corticoaccumbens slice preparations. Thus bursting PFC activity recruits local
      inhibition in the NA, shaping responses of projection neurons with a
      topographical arrangement that allows inhibition among parallel corticoaccumbens
      channels. The data indicate a high order of information processing within
      striatal circuits that should be considered in models of basal ganglia function
      and disease.

PMID- 19176611
TI  - Self-motion signals in vestibular nuclei neurons projecting to the thalamus in
      the alert squirrel monkey.
AB  - Sixty vestibular nuclei neurons antidromically activated by electrical
      stimulation of the ventroposterior thalamus were recorded in two alert squirrel
      monkeys. The majority of these neurons were monosynaptically activated by
      vestibular nerve electrical stimulation. Forty-seven neurons responded to animal
      rotations around the earth-vertical axis; 16 of them also responded to
      translations in the horizontal plane. The mean sensitivity to 0.5-Hz rotations of
      80 degrees /s velocity was 0.40 +/- 0.31 spikes.s(-1).deg(-1).s(-1). Rotational
      responses were in phase with stimulus velocity. Sensitivities to 0.5-Hz
      translations of 0.1 g acceleration varied from 92.2 to 359 spikes.s(-1).g(-1) and
      response phases varied from 10.1 degrees lead to -98 degrees lag. The firing
      behavior in 28 neurons was studied during rotation of the whole animal, of the
      trunk, and voluntary and involuntary rotations of the head. Two classes of
      vestibulothalamic neurons were distinguished. One class of neurons generated
      signals related to movement of the head that were similar either when the head
      and trunk move together or when the head moves on the stationary trunk. A
      fraction of these neurons fired during involuntary head movements only. A second
      class of neurons generated signals related to movement of the trunk. They
      responded when the trunk moved alone or simultaneously with the head, but did not
      respond to head rotations while the trunk was stationary.

PMID- 19176612
TI  - Evidence for a critical period in the development of excitability and potassium
      currents in mouse lumbar superficial dorsal horn neurons.
AB  - The output of superficial dorsal horn (SDH; laminae I-II) neurons is critical for
      processing nociceptive, thermal, and tactile information. Like other neurons, the
      combined effects of synaptic inputs and intrinsic membrane properties determine
      their output. It is well established that peripheral synaptic inputs to SDH
      neurons undergo extensive reorganization during pre- and postnatal development.
      It is unclear, however, how membrane properties or the subthreshold whole cell
      currents that shape SDH neuron output change during this period. Here we assess
      the intrinsic membrane properties and whole cell currents in mouse SDH neurons
      during late embryonic and early postnatal development (E15-P25). Transverse
      slices were prepared from lumbar spinal cord and whole cell recordings were
      obtained at 32 degrees C. During this developmental period resting membrane
      potential (RMP) became more hyperpolarized (by approximately 10 mV, E15-E17 vs.
      P21-P25) and input resistance decreased (1,074 +/- 78 vs. 420 +/- 27 MOmega). In
      addition, action potential (AP) amplitude and AP afterhyperpolarization
      increased, whereas AP half-width decreased. Before and after birth (E15-P10), AP
      discharge evoked by intracellular current injection was limited to a single AP at
      depolarization onset in many neurons (>41%). In older animals (P11-P25) this
      changed, with AP discharge consisting of brief bursts at current onset (
      approximately 46% of neurons). Investigation of major subthreshold whole cell
      currents showed the rapid A-type potassium current (I(Ar)) dominated at all ages
      examined (90% of neurons at E15-E17, decreasing to >50% after P10). I(Ar)
      expression levels, based on peak current amplitude, increased during development.
      Steady-state inactivation and activation for I(Ar) were slightly less potent in
      E15-E17 versus P21-P25 neurons at potentials near RMP (-55 mV). Together, our
      data indicate that intrinsic properties and I(Ar) expression change dramatically
      in SDH neurons during development, with the greatest alterations occurring on
      either side of a critical period, P6-P10.

PMID- 19176613
TI  - Zinc modulation of hemi-gap-junction channel currents in retinal horizontal
      cells.
AB  - Hemi-gap-junction (HGJ) channels of retinal horizontal cells (HCs) function as
      transmembrane ion channels that are modulated by voltage and calcium. As an
      endogenous retinal neuromodulator, zinc, which is coreleased with glutamate at
      photoreceptor synapses, plays an important role in shaping visual signals by
      acting on postsynaptic HCs in vivo. To understand more fully the regulation and
      function of HC HGJ channels, we examined the effect of Zn(2+) on HGJ channel
      currents in bass retinal HCs. Hemichannel currents elicited by depolarization in
      Ca(2+)-free medium and in 1 mM Ca(2+) medium were significantly inhibited by
      extracellular Zn(2+). The inhibition by Zn(2+) of hemichannel currents was dose
      dependent with a half-maximum inhibitory concentration of 37 microM. Compared
      with other divalent cations, Zn(2+) exhibited higher inhibitory potency, with the
      order being Zn(2+) > Cd(2+) approximately Co(2+) > Ca(2+) > Ba(2+) > Mg(2+).
      Zn(2+) and Ca(2+) were found to modulate HGJ channels independently in additivity
      experiments. Modification of histidine residues with N-bromosuccinimide
      suppressed the inhibitory action of Zn(2+), whereas modification of cysteine
      residues had no significant effect on Zn(2+) inhibition. Taken together, these
      results suggest that zinc acts on HGJ channels in a calcium-independent way and
      that histidine residues on the extracellular domain of HGJ channels mediate the
      inhibitory action of zinc.

PMID- 19176614
TI  - Dendritic excitability and neuronal morphology as determinants of synaptic
      efficacy.
AB  - The ability to trigger neuronal spiking activity is one of the most important
      functional characteristics of synaptic inputs and can be quantified as a measure
      of synaptic efficacy (SE). Using model neurons with both highly simplified and
      real morphological structures (from a single cylindrical dendrite to a
      hippocampal granule cell, CA1 pyramidal cell, spinal motoneuron, and retinal
      ganglion neurons) we found that SE of excitatory inputs decreases with the
      distance from the soma and active nonlinear properties of the dendrites can
      counterbalance this global effect of attenuation. This phenomenon is frequency
      dependent, with a more prominent gain in SE observed at lower levels of
      background input-output neuronal activity. In contrast, there are no significant
      differences in SE between passive and active dendrites under higher frequencies
      of background activity. The influence of the nonuniform distribution of active
      properties on SE is also more prominent at lower background frequencies. In
      models with real morphologies, the effect of active dendritic conductances
      becomes more dramatic and inverts the SE relationship between distal and proximal
      locations. In active dendrites, distal synapses have higher efficacy than that of
      proximal ones because of arising dendritic spiking in thin branches with high
      input resistance. Lower levels of dendritic excitability can make SE independent
      of the distance from the soma. Although increasing dendritic excitability may
      boost SE of distal synapses in real neurons, it may actually reduce overall SE.
      The results are robust with respect to morphological variation and biophysical
      properties of the model neurons. The model of CA1 pyramidal cell with realistic
      distributions of dendritic conductances demonstrated important roles of
      hyperpolarization-activated (h-) current and A-type K(+) current in controlling
      the efficacy of single synaptic inputs and overall SE differently in basal and
      apical dendrites.

PMID- 19176615
TI  - Identification of TRIM23 as a cofactor involved in the regulation of NF-kappaB by
      human cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) regulates NF-kappaB during infection by a variety of
      mechanisms. For example, the HCMV gene product, UL144, is known to activate NF
      kappaB in a tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)
      dependent manner, causing the upregulation of the chemokine CCL22 (MDC). Viral
      UL144 is expressed from the UL/b' region of the HCMV genome at early times
      postinfection and is a TNFR1-like homologue. Despite this homology to the TNFR1
      receptor superfamily, UL144 does not bind to members of the TNF ligand
      superfamily. We show here that the upregulation of NF-kappaB by UL144 is
      dependent upon cellular tripartite motif 23 (TRIM23) protein. We propose a
      mechanism by which UL144 activates NF-kappaB through a direct interaction with
      the cellular protein TRIM23 in a complex containing TRAF6. In contrast, TRIM23 is
      not involved in conventional double-stranded RNA signaling via NF-kappaB.
      Therefore, we present a novel role for TRIM23 that is specific to UL144-mediated
      activation of NF-kappaB during the course of virus infection.

PMID- 19176616
TI  - Noncytolytic clearance of sindbis virus infection from neurons by gamma
      interferon is dependent on Jak/STAT signaling.
AB  - The alphavirus Sindbis virus (SINV) causes encephalomyelitis in mice by infecting
      neurons of the brain and spinal cord. The outcome is age dependent. Young animals
      develop fatal disease, while older animals recover from infection. Recovery
      requires noncytolytic clearance of SINV from neurons, and gamma interferon (IFN
      gamma) is an important contributor to clearance in vivo. IFN-gamma-dependent
      clearance has been studied using immortalized CSM14.1 rat neuronal cells that can
      be differentiated in vitro. Previous studies have shown that differentiated, but
      not undifferentiated, cells develop prolonged SINV replication and respond to IFN
      gamma treatment with noncytolytic clearance of virus preceded by suppression of
      genomic viral RNA synthesis and reactivation of cellular protein synthesis. To
      determine the signaling mechanisms responsible for clearance, the responses of
      SINV-infected differentiated neurons to IFN-gamma were examined. IFN-gamma
      treatment of SINV-infected differentiated CSM14.1 cells, AP-7 olfactory neuronal
      cells, and primary dorsal root ganglia neurons triggered prolonged Stat-1
      Tyr(701) phosphorylation, Stat-1 Ser(727) phosphorylation, and transient Stat-5
      phosphorylation. Inhibition of Jak kinase activity with Jak inhibitor I
      completely reversed the neuroprotective and antiviral activities of IFN-gamma in
      differentiated cells. We conclude that activation of the Jak/Stat pathway is the
      primary mechanism for IFN-gamma-mediated clearance of SINV infection from mature
      neurons.

PMID- 19176617
TI  - Functional replacement of a domain in the rubella virus p150 replicase protein by
      the virus capsid protein.
AB  - The rubella virus (RUBV) capsid (C) protein rescues mutants with a lethal
      deletion between two in-frame NotI sites in the P150 replicase gene, a deletion
      encompassing nucleotides 1685 to 2192 of the RUBV genome and amino acids (aa) 548
      to 717 of P150 (which has a total length of 1,301 aa). The complete domain
      rescuable by the C protein was mapped to aa 497 to 803 of P150. Introduction of
      aa 1 to 277 of the C protein (lacking the C-terminal E2 signal sequence) between
      the NotI sites in the P150 gene in a replicon construct yielded a viable
      construct that synthesized viral RNA with wild-type kinetics, indicating that C
      and this region of P150 share a common function. Further genetic analysis
      revealed that an arginine-rich motif between aa 60 and 68 of the C protein was
      necessary for the rescue of DeltaNotI deletion mutants and substituted for an
      arginine-rich motif between aa 731 and 735 of the P150 protein when the C protein
      was introduced into P150. Possible common functions shared by these arginine-rich
      motifs include RNA binding and interaction with cell proteins.

PMID- 19176618
TI  - Foot-and-mouth disease virus can induce a specific and rapid CD4+ T-cell
      independent neutralizing and isotype class-switched antibody response in naive
      cattle.
AB  - The role of T-lymphocyte subsets in recovery from foot-and-mouth disease virus
      (FMDV) infection in calves was investigated by administering subset-specific
      monoclonal antibodies. The depletion of circulating CD4(+) or WC1(+) gammadelta T
      cells was achieved for a period extending from before challenge to after
      resolution of viremia and peak clinical signs, whereas CD8(+) cell depletion was
      only partial. The depletion of CD4(+) cells was also confirmed by analysis of
      lymph node biopsy specimens 5 days postchallenge. Depletion with anti-WC1 and
      anti-CD8 antibodies had no effect on the kinetics of infection, clinical signs,
      and immune responses following FMDV infection. Three of the four CD4(+) T-cell
      depleted calves failed to generate an antibody response to the nonstructural
      polyprotein 3ABC but generated a neutralizing antibody response similar to that
      in the controls, including rapid isotype switching to immunoglobulin G antibody.
      We conclude that antibody responses to sites on the surface of the virus capsid
      are T cell independent, whereas those directed against the nonstructural proteins
      are T cell dependent. CD4 depletion was found to substantially inhibit antibody
      responses to the G-H peptide loop VP1(135-156) on the viral capsid, indicating
      that responses to this particular site, which has a more mobile structure than
      other neutralizing sites on the virus capsid, are T cell dependent. The depletion
      of CD4(+) T cells had no adverse effect on the magnitude or duration of clinical
      signs or clearance of virus from the circulation. Overall, we conclude that
      CD4(+) T-cell-independent antibody responses play a major role in the resolution
      of foot-and-mouth disease in cattle.

PMID- 19176619
TI  - Organ-specific attenuation of murine hepatitis virus strain A59 by replacement of
      catalytic residues in the putative viral cyclic phosphodiesterase ns2.
AB  - The Murine hepatitis virus (MHV) strain A59 ns2 protein is a 30-kDa nonstructural
      protein that is expressed from a subgenomic mRNA in the cytoplasm of virus
      infected cells. Its homologs are also encoded in other closely related group 2a
      coronaviruses and more distantly related toroviruses. Together, these proteins
      comprise a subset of a large superfamily of 2H phosphoesterase proteins that are
      distinguished by a pair of conserved His-x-Thr/Ser motifs encompassing
      catalytically important residues. We have used a vaccinia virus-based reverse
      genetic system to produce recombinant viruses encoding ns2 proteins with single
      amino-acid substitutions in, or adjacent to, these conserved motifs, namely, inf
      ns2 H46A, inf-ns2 S48A, inf-ns2-S120A, and inf-ns2-H126R. All of the mutant
      viruses replicate in mouse 17 clone 1 fibroblast cells and mouse embryonic cells
      to the same extent as the parental wild-type recombinant virus, inf-MHV-A59.
      However, compared to inf-MHV-A59, the inf-ns2 H46A and inf-ns2-H126R mutants are
      highly attenuated for replication in mouse liver following intrahepatic
      inoculation. Interestingly, none of the mutant viruses were attenuated for
      replication in mouse brain following intracranial inoculation. These results show
      that the ns2 protein of MHV-A59 has an important role in virus pathogenicity and
      that a substitution of the histidine residues of the MHV-A59 ns2 His-x-Thr/Ser
      motifs is critical for virus virulence in the liver but not in the brain. This
      novel phenotype suggests a strategy to investigate the function of the MHV-A59
      ns2 protein involving the search for organ-specific proteins or RNAs that react
      differentially to wild-type and mutant ns2 proteins.

PMID- 19176620
TI  - Transcriptional coactivators are not required for herpes simplex virus type 1
      immediate-early gene expression in vitro.
AB  - Virion protein 16 (VP16) of herpes simplex virus type 1 (HSV-1) is a potent
      transcriptional activator of viral immediate-early (IE) genes. The VP16
      activation domain can recruit various transcriptional coactivators to target gene
      promoters. However, the role of transcriptional coactivators in HSV-1 IE gene
      expression during lytic infection had not been fully defined. We showed
      previously that transcriptional coactivators such as the p300 and CBP histone
      acetyltransferases and the BRM and Brg-1 chromatin remodeling complexes are
      recruited to viral IE gene promoters in a manner dependent mostly on the presence
      of the activation domain of VP16. In this study, we tested the hypothesis that
      these transcriptional coactivators are required for viral IE gene expression
      during infection of cultured cells. The disrupted expression of the histone
      acetyltransferases p300, CBP, PCAF, and GCN5 or the BRM and Brg-1 chromatin
      remodeling complexes did not diminish IE gene expression. Furthermore, IE gene
      expression was not impaired in cell lines that lack functional p300, or BRM and
      Brg-1. We also tested whether these coactivators are required for the VP16
      dependent induction of IE gene expression from transcriptionally inactive viral
      genomes associated with high levels of histones in cultured cells. We found that
      the disruption of coactivators also did not affect IE gene expression in this
      context. Thus, we conclude that the transcriptional coactivators that can be
      recruited by VP16 do not contribute significantly to IE gene expression during
      lytic infection or the induction of IE gene expression from nucleosomal templates
      in vitro.

PMID- 19176621
TI  - Herpes simplex virus utilizes the large secretory vesicle pathway for anterograde
      transport of tegument and envelope proteins and for viral exocytosis from growth
      cones of human fetal axons.
AB  - Axonal transport of herpes simplex virus (HSV-1) is essential for viral infection
      and spread in the peripheral nervous system of the host. Therefore, the virus
      probably utilizes existing active transport and targeting mechanisms in neurons
      for virus assembly and spread from neurons to skin. In the present study, we used
      transmission immunoelectron microscopy to investigate the nature and origin of
      vesicles involved in the anterograde axonal transport of HSV-1 tegument and
      envelope proteins and of vesicles surrounding partially and fully enveloped
      capsids in growth cones. This study aimed to elucidate the mechanism of virus
      assembly and exit from axons of human fetal dorsal root ganglia neurons. We
      demonstrated that viral tegument and envelope proteins can travel in axons
      independently of viral capsids and were transported to the axon terminus in two
      types of transport vesicles, tubulovesicular membrane structures and large dense
      cored vesicles. These vesicles and membrane carriers were derived from the trans
      Golgi network (TGN) and contained key proteins, such as Rab3A, SNAP-25, GAP-43,
      and kinesin-1, involved in the secretory and exocytic pathways in axons. These
      proteins were also observed on fully and partially enveloped capsids in growth
      cones and on extracellular virions. Our findings provide further evidence to the
      subassembly model of separate transport in axons of unenveloped capsids from
      envelope and tegument proteins with final virus assembly occurring at the axon
      terminus. We postulate that HSV-1 capsids invaginate tegument- and envelope
      bearing TGN-derived vesicles and utilize the large secretory vesicle pathway of
      exocytosis for exit from axons.

PMID- 19176622
TI  - Identification of potential recombination breakpoints in human parechoviruses.
AB  - Based on a comparison of the phylogeny of two distant regions, evidence has been
      found for recombination within parechoviruses. However, recombination breakpoints
      could not be detected in this way. We searched for potential recombination
      breakpoints in parechovirus by analysis of complete parechovirus sequences,
      including a newly isolated strain. Bootscan analysis demonstrated that
      parechoviruses are mosaic viruses build of regions related to corresponding
      genomic regions of other parechoviruses. With a genetic algorithm for
      recombination detection, sites for recombination were found. Analysis of partial
      sequences, as defined by recombination breakpoints, showed phylogenetic
      segregation between regions.

PMID- 19176623
TI  - Non-cleavage site gag mutations in amprenavir-resistant human immunodeficiency
      virus type 1 (HIV-1) predispose HIV-1 to rapid acquisition of amprenavir
      resistance but delay development of resistance to other protease inhibitors.
AB  - In an attempt to determine whether mutations in Gag in human immunodeficiency
      virus type 1 (HIV-1) variants selected with a protease inhibitor (PI) affect the
      development of resistance to the same or a different PI(s), we generated multiple
      infectious HIV-1 clones carrying mutated Gag and/or mutated protease proteins
      that were identified in amprenavir (APV)-selected HIV-1 variants and examined
      their virological characteristics. In an HIV-1 preparation selected with APV (33
      passages, yielding HIV(APVp33)), we identified six mutations in protease and six
      apparently critical mutations at cleavage and non-cleavage sites in Gag. An
      infectious recombinant clone carrying the six protease mutations but no Gag
      mutations failed to replicate, indicating that the Gag mutations were required
      for the replication of HIV(APVp33). An infectious recombinant clone that carried
      wild-type protease and a set of five Gag mutations
      (rHIV(WTpro)(12/75/219/390/409gag)) replicated comparably to wild-type HIV-1;
      however, when exposed to APV, rHIV(WTpro)(12/75/219/390/409gag) rapidly acquired
      APV resistance. In contrast, the five Gag mutations significantly delayed the
      acquisition of HIV-1 resistance to ritonavir and nelfinavir (NFV). Recombinant
      HIV-1 clones containing NFV resistance-associated mutations, such as D30N and
      N88S, had increased susceptibilities to APV, suggesting that antiretroviral
      regimens including both APV and NFV may bring about favorable antiviral efficacy.
      The present data suggest that the preexistence of certain Gag mutations related
      to PI resistance can accelerate the emergence of resistance to the PI and delay
      the acquisition of HIV resistance to other PIs, and these findings should have
      clinical relevance in the therapy of HIV-1 infection with PI-including regimens.

PMID- 19176624
TI  - Usage of integrin and heparan sulfate as receptors for mouse adenovirus type 1.
AB  - Adenovirus fiber knobs are the capsid components that interact with binding
      receptors on cells, while an Arg-Gly-Asp (RGD) sequence usually found in the
      penton base protein is important for the interaction of most adenoviruses with
      integrin entry receptors. Mouse adenovirus type 1 (MAV-1) lacks an RGD sequence
      in the virion penton base protein. We tested whether an RGD sequence found in the
      MAV-1 fiber knob plays a role in infection. Treatment of cells with a competitor
      RGD peptide or a purified recombinant RGD-containing fiber knob prior to
      infection resulted in reduced virus yields compared to those of controls,
      indicating the importance of the RGD sequence for infection. An investigation of
      the role of integrins as possible receptors showed that MAV-1 yields were reduced
      in the presence of EDTA, an inhibitor of integrin binding, and in the presence of
      anti-alpha(v) integrin antibody. Moreover, mouse embryo fibroblasts that were
      genetically deficient in alpha(v) integrin yielded less virus, supporting the
      hypothesis that alpha(v) integrin is a likely receptor for MAV-1. We also
      investigated whether glycosaminoglycans play a role in MAV-1 infection.
      Preincubation of MAV-1 with heparin, a heparan sulfate glycosaminoglycan analog,
      resulted in a decrease in MAV-1 virus yields. Reduced MAV-1 infectivity was also
      found with cells that genetically lack heparan sulfate or cells that were treated
      with heparinase I. Cumulatively, our data demonstrate that the RGD sequence in
      the MAV-1 fiber knob plays a role in infection by MAV-1, alpha(v) integrin acts
      as a receptor for the virus, and cell surface heparin sulfate glycosaminoglycans
      are important in MAV-1 infection.

PMID- 19176625
TI  - Identification of functional domains in reovirus replication proteins muNS and
      mu2.
AB  - Mammalian reoviruses are nonenveloped particles containing a genome of 10 double
      stranded RNA (dsRNA) gene segments. Reovirus replication occurs within viral
      inclusions, which are specialized nonmembranous cytoplasmic organelles formed by
      viral nonstructural and structural proteins. Although these structures serve as
      sites for several major events in the reovirus life cycle, including dsRNA
      synthesis, gene segment assortment, and genome encapsidation, biochemical
      mechanisms of virion morphogenesis within inclusions have not been elucidated
      because much remains unknown about inclusion anatomy and functional organization.
      To better understand how inclusions support viral replication, we have used RNA
      interference (RNAi) and reverse genetics to define functional domains in two
      inclusion-associated proteins, muNS and mu2, which are interacting partners
      essential for inclusion development and viral replication. Removal of muNS N
      terminal sequences required for association with mu2 or another muNS-binding
      protein, sigmaNS, prevented the capacity of muNS to support viral replication
      without affecting inclusion formation, indicating that muNS-mu2 and muNS-sigmaNS
      interactions are necessary for inclusion function but not establishment. In
      contrast, introduction of changes into the muNS C-terminal region, including
      sequences that form a putative oligomerization domain, precluded inclusion
      formation as well as viral replication. Mutational analysis of mu2 revealed a
      critical dependence of viral replication on an intact nucleotide/RNA
      triphosphatase domain and an N-terminal cluster of basic amino acid residues
      conforming to a nuclear localization motif. Another domain in mu2 governs the
      capacity of viral inclusions to affiliate with microtubules and thereby modulates
      inclusion morphology, either globular or filamentous. However, viral variants
      altered in inclusion morphology displayed equivalent replication efficiency.
      These studies reveal a modular functional organization of inclusion proteins muNS
      and mu2, define the importance of specific amino acid sequences and motifs in
      these proteins for viral replication, and demonstrate the utility of
      complementary RNAi-based and reverse genetic approaches for studies of reovirus
      replication proteins.

PMID- 19176626
TI  - Distinct profiles of cytotoxic granules in memory CD8 T cells correlate with
      function, differentiation stage, and antigen exposure.
AB  - Cytotoxic CD8 T cells exert their antiviral and antitumor activity primarily
      through the secretion of cytotoxic granules. Degranulation activity and cytotoxic
      granules (perforin plus granzymes) generally define CD8 T cells with cytotoxic
      function. In this study, we have investigated the expression of granzyme K (GrmK)
      in comparison to that of GrmA, GrmB, and perforin. The expression of the
      cytotoxic granules was assessed in virus-specific CD8 T cells specific to
      influenza virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human
      immunodeficiency virus type 1 (HIV-1). We observed a dichotomy between GrmK and
      perforin expression in virus-specific CD8 T cells. The profile in influenza virus
      specific CD8 T cells was perforin(-) GrmB(-) GrmA(+/-) GrmK(+); in CMV-specific
      cells, it was perforin(+) GrmB(+) GrmA(+) GrmK(-/+); and in EBV- and HIV-1
      specific cells, it was perforin(-/+) GrmB(+) GrmA(+) GrmK(+). On the basis of the
      delineation of memory and effector CD8 T cells with CD45RA and CD127, the GrmK(+)
      profile was associated with early-stage memory CD8 T-cell differentiation, the
      perforin(+) GrmB(+) GrmA(+) profile with advanced-stage differentiation, and the
      GrmB(+) GrmA(+) Grmk(+) profile with intermediate-stage differentiation.
      Furthermore, perforin and GrmB but not GrmA and GrmK correlated with cytotoxic
      activity. Finally, changes in antigen exposure in vitro and in vivo during
      primary HIV-1 infection and vaccination modulated cytotoxic granule profiles.
      These results advance our understanding of the relationship between distinct
      profiles of cytotoxic granules in memory CD8 T cells and function,
      differentiation stage, and antigen exposure.

PMID- 19176627
TI  - The infected cell protein 0 encoded by bovine herpesvirus 1 (bICP0) associates
      with interferon regulatory factor 7 and consequently inhibits beta interferon
      promoter activity.
AB  - The bICP0 protein encoded by bovine herpesvirus 1 stimulates productive infection
      and viral gene expression but inhibits interferon (IFN)-dependent transcription.
      bICP0 inhibits beta IFN (IFN-beta) promoter activity and induces degradation of
      IFN regulatory factor 3 (IRF3). Although bICP0 inhibits the trans-activation
      activity of IRF7, IRF7 protein levels are not reduced. In this study, we
      demonstrate that bICP0 is associated with IRF7. Furthermore, bICP0 inhibits the
      ability of IRF7 to trans-activate the IFN-beta promoter in the absence of IRF3
      expression. The interaction between bICP0 and IRF7 correlates with reduced trans
      activation of the IFN-beta promoter by IRF7.

PMID- 19176628
TI  - Adenovirus serotype 5 L4-22K and L4-33K proteins have distinct functions in
      regulating late gene expression.
AB  - Adenoviruses express up to 20 distinct mRNAs from five major late transcription
      unit (MLTU) regions, L1 to L5, by differential splicing and polyadenylation of
      the primary transcript. MLTU expression is regulated at transcriptional and
      posttranscriptional levels. The L4-33K protein acts as a splicing factor to
      upregulate several MLTU splice acceptor sites as the late phase progresses. The
      L4 region also expresses a 22K protein whose sequence is related to the sequence
      of L4-33K. L4-22K is shown here also to have an important role in regulating the
      pattern of MLTU gene expression. An adenovirus genome containing a stop codon in
      the L4-22K open reading frame expressed low levels of both structural and
      nonstructural late proteins compared to the wild-type (wt) adenovirus genome; a
      decrease in intermediate proteins, IVa2 and IX, was also observed. However, early
      protein synthesis and replication were unaffected by the absence of L4-22K.
      Intermediate and late protein expression was restored to wt levels by L4-22K
      expressed in trans but not by L4-33K. Increased MLTU promoter activity, resulting
      from stabilization of the transcriptional activator IVa2 by L4-22K, made a small
      contribution to this restoration of late gene expression. However, the principal
      effect of L4-22K was on the processing of MLTU RNA into specific cytoplasmic
      mRNA. L4-22K selectively increased expression of penton mRNA and protein, whereas
      splicing to create penton mRNA is known not to be increased by L4-33K. These
      results indicate that L4-22K plays a key role in the early-late switch in MLTU
      expression, additional to and distinct from the role of L4-33K.

PMID- 19176629
TI  - Nonintegrating lentivector vaccines stimulate prolonged T-cell and antibody
      responses and are effective in tumor therapy.
AB  - Lentiviral vectors (lentivectors) are effective for stimulation of cell-mediated
      and humoral immunity following subcutaneous and intramuscular immunization.
      However, lentivector genome integration carries a risk of perturbation of host
      gene expression. Here, we demonstrate that lentivectors with multiple mutations
      that prevent integration are also effective immunogens. First, systemic CD8(+) T
      cell responses to the model antigen ovalbumin were detected following
      subcutaneous injection of nonintegrating lentivectors. Transfer of transgenic OT1
      T cells demonstrated that antigen presentation persisted for at least 30 days.
      Furthermore, an enhanced CD8(+) T-cell response, peaking at 7 days, was
      stimulated by coexpression of p38 MAP kinase or an NF-kappaB activator from the
      same vector. Second, we demonstrated systemic CD8(+) T-cell and antibody
      responses to the secreted hepatitis B virus (HBV) surface antigen expressed from
      a nonintegrating lentivector injected intramuscularly. The induction,
      specificity, and kinetics of antibody production closely mimicked those of
      natural HBV infection. In this case, both the vector genome and the immune
      response were maintained for at least 2 months. Together, our data indicate that
      nonintegrating lentivectors can be employed to generate effective vaccines.

PMID- 19176630
TI  - The region approximately between amino acids 81 and 137 of proteinase K-resistant
      PrPSc is critical for the infectivity of the Chandler prion strain.
AB  - Although the major component of the prion is believed to be the oligomer of
      PrP(Sc), little information is available concerning regions on the PrP(Sc)
      molecule that affect prion infectivity. During the analysis of PrP(Sc) molecules
      from various prion strains, we found that PrP(Sc) of the Chandler strain showed a
      unique property in the conformational-stability assay, and this property appeared
      to be useful for studying the relationship between regions of the PrP(Sc)
      molecule and prion infectivity. Thus, we analyzed PrP(Sc) of the Chandler strain
      in detail and analyzed the infectivities of the N-terminally denatured and
      truncated forms of proteinase K-resistant PrP. The N-terminal region of PrP(Sc)
      of the Chandler strain showed region-dependent resistance to guanidine
      hydrochloride (GdnHCl) treatment. The region approximately between amino acids
      (aa) 81 and 137 began to be denatured by treatment with 1.5 M GdnHCl. Within this
      stretch, the region comprising approximately aa 81 to 90 was denatured almost
      completely by 2 M GdnHCl. Furthermore, the region approximately between aa 90 and
      137 was denatured completely by 3 M GdnHCl. However, the C-terminal region
      thereafter was extremely resistant to the GdnHCl treatment. This property was not
      observed in PrP(Sc) molecules of other prion strains. Denaturation of the region
      between aa 81 and 137 by 3 M GdnHCl significantly prolonged the incubation
      periods in mice compared to that for the untreated control. More strikingly, the
      denaturation and removal of this region nearly abolished the infectivity. This
      finding suggests that the conformation of the region between aa 81 and 137 of the
      Chandler strain PrP(Sc) molecule is directly associated with prion infectivity.

PMID- 19176631
TI  - Alphavirus-adjuvanted norovirus-like particle vaccines: heterologous, humoral,
      and mucosal immune responses protect against murine norovirus challenge.
AB  - The development of an effective norovirus vaccine likely requires the capacity to
      protect against infection with multiple norovirus strains. Advanced recombinant
      genetic systems and the recent discovery of a mouse-tropic norovirus strain (MNV)
      provide robust model systems for vaccine efficacy studies. We coadministered
      multivalent norovirus-like particle (VLP) vaccines with alphavirus adjuvant
      particles to mice and evaluated homotypic and heterotypic humoral and protective
      immunity to human and murine norovirus strains. Multivalent VLP vaccines induced
      robust receptor-blocking antibody responses to heterologous human strains not
      included in the vaccine composition. Inclusion of alphavirus adjuvants in the
      inoculum significantly augmented VLP-induced systemic and mucosal immunity
      compared to the responses induced by low-dose CpG DNA, validating the utility of
      such adjuvants with VLP antigens. Furthermore, multivalent vaccination, either
      including or excluding MNV VLP, resulted in significantly reduced viral loads
      following MNV challenge. Passive transfer of sera from mice monovalently
      vaccinated with MNV VLP to immunodeficient or immunocompetent mice protected
      against MNV infection; however, adoptive transfer of purified CD4(+) or CD8(+)
      cells did not influence viral loads in murine tissues. Together, these data
      suggest that humoral immunity induced by multivalent norovirus vaccines may
      protect against heterologous norovirus challenge.

PMID- 19176632
TI  - Induction of a striking systemic cytokine cascade prior to peak viremia in acute
      human immunodeficiency virus type 1 infection, in contrast to more modest and
      delayed responses in acute hepatitis B and C virus infections.
AB  - Characterization of the immune responses induced in the initial stages of human
      immunodeficiency virus type 1 (HIV-1) infection is of critical importance for an
      understanding of early viral pathogenesis and prophylactic vaccine design. Here,
      we used sequential plasma samples collected during the eclipse and exponential
      viral expansion phases from subjects acquiring HIV-1 (or, for comparison,
      hepatitis B virus [HBV]or hepatitis C virus [HCV]) to determine the nature and
      kinetics of the earliest systemic elevations in cytokine and chemokine levels in
      each infection. Plasma viremia was quantitated over time, and levels of 30
      cytokines and chemokines were measured using Luminex-based multiplex assays and
      enzyme-linked immunosorbent assays. The increase in plasma viremia in acute HIV-1
      infection was found to be associated with elevations in plasma levels of multiple
      cytokines and chemokines, including rapid and transient elevations in alpha
      interferon (IFN-alpha) and interleukin-15 (IL-15) levels; a large increase in
      inducible protein 10 (IP-10) levels; rapid and more-sustained increases in tumor
      necrosis factor alpha and monocyte chemotactic protein 1 levels; more slowly
      initiated elevations in levels of additional proinflammatory factors including IL
      6, IL-8, IL-18, and IFN-gamma; and a late-peaking increase in levels of the
      immunoregulatory cytokine IL-10. Notably, there was comparatively little
      perturbation in plasma cytokine levels during the same phase of HBV infection and
      a delayed response of more intermediate magnitude in acute HCV infection,
      indicating that the rapid activation of a striking systemic cytokine cascade is
      not a prerequisite for viral clearance (which occurs in a majority of HBV
      infected individuals). The intense early cytokine storm in acute HIV-1 infection
      may have immunopathological consequences, promoting immune activation, viral
      replication, and CD4(+) T-cell loss.

PMID- 19176633
TI  - Malignancy in children with trisomy 21.
AB  - Patients with Down syndrome (DS) display a unique spectrum of malignancies, with
      a 10- to 20-fold higher risk of acute leukemias, and a markedly lower incidence
      of solid tumors. This review discusses the current understanding of the basis for
      this distinctive pattern of cancer incidence and the clinical and biologic
      features of the malignant disorders most frequent in DS individuals: transient
      myeloproliferative disease, acute megakaryoblastic leukemia, and acute
      lymphoblastic leukemia. We also review distinctive pharmacogenetic issues,
      highlighting the differential chemosensitivity and toxicity profiles of DS
      patients compared with the general population, and epidemiologic studies of
      protective and adverse environmental risk factors for the development of
      leukemia.

PMID- 19176634
TI  - Federal fiscal blueprint dodges health concerns.

PMID- 19176635
TI  - A population-based study of the drug interaction between proton pump inhibitors
      and clopidogrel.
AB  - BACKGROUND: Most proton pump inhibitors inhibit the bioactivation of clopidogrel
      to its active metabolite. The clinical significance of this drug interaction is
      unknown. METHODS: We conducted a population-based nested case-control study among
      patients aged 66 years or older who commenced clopidogrel between Apr. 1, 2002,
      and Dec. 31, 2007, following hospital discharge after treatment of acute
      myocardial infarction. The cases in our study were those readmitted with acute
      myocardial infarction within 90 days after discharge. We performed a secondary
      analysis considering events within 1 year. Event-free controls (at a ratio of
      3:1) were matched to cases on age, percutaneous coronary intervention and a
      validated risk score. We categorized exposure to proton pump inhibitors before
      the index date as current (within 30 days), previous (31-90 days) or remote (91
      180 days). RESULTS: Among 13 636 patients prescribed clopidogrel following acute
      myocardial infarction, we identified 734 cases readmitted with myocardial
      infarction and 2057 controls. After extensive multivariable adjustment, current
      use of proton pump inhibitors was associated with an increased risk of
      reinfarction (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.03
      1.57). We found no association with more distant exposure to proton pump
      inhibitors or in multiple sensitivity analyses. In a stratified analysis,
      pantoprazole, which does not inhibit cytochrome P450 2C19, had no association
      with readmission for myocardial infarction (adjusted OR 1.02, 95% CI 0.70-1.47).
      INTERPRETATION: Among patients receiving clopidogrel following acute myocardial
      infarction, concomitant therapy with proton pump inhibitors other than
      pantoprazole was associated with a loss of the beneficial effects of clopidogrel
      and an increased risk of reinfarction.

PMID- 19176636
TI  - Involvement of nicotinic and muscarinic receptors in the endogenous cholinergic
      modulation of the balance between excitation and inhibition in the young rat
      visual cortex.
AB  - This study aims to clarify how endogenous release of cortical acetylcholine (ACh)
      modulates the balance between excitation and inhibition evoked in visual cortex.
      We show that electrical stimulation in layer 1 produced a significant release of
      ACh measured intracortically by chemoluminescence and evoked a composite synaptic
      response recorded intracellularly in layer 5 pyramidal neurons of rat visual
      cortex. The pharmacological specificity of the ACh neuromodulation was determined
      from the continuous whole-cell voltage clamp measurement of stimulation-locked
      changes of the input conductance during the application of cholinergic agonists
      and antagonists. Blockade of glutamatergic and gamma-aminobutyric acid
      (GABAergic) receptors suppressed the evoked response, indicating that stimulation
      induced release of ACh does not directly activate a cholinergic synaptic
      conductance in recorded neurons. Comparison of cytisine and mecamylamine effects
      on nicotinic receptors showed that excitation is enhanced by endogenous evoked
      release of ACh through the presynaptic activation of alpha(*)beta4 receptors
      located on glutamatergic fibers. DHbetaE, the selective alpha4beta2 nicotinic
      receptor antagonist, induced a depression of inhibition. Endogenous ACh could
      also enhance inhibition by acting directly on GABAergic interneurons, presynaptic
      to the recorded cell. We conclude that endogenous-released ACh amplifies the
      dominance of the inhibitory drive and thus decreases the excitability and sensory
      responsiveness of layer 5 pyramidal neurons.

PMID- 19176637
TI  - Different spatial scales of shape similarity representation in lateral and
      ventral LOC.
AB  - We investigated the relationship between stimulus similarity for a set of
      parameterized shapes and the spatial scale of neural representation within
      subregions of the lateral occipital complex (LOC) using a carryover functional
      magnetic resonance imaging design. In ventral but not lateral LOC, a linear
      recovery from adaptation proportional to shape dissimilarity was seen. In
      contrast, a strong correspondence of the distributed neural pattern and stimulus
      similarity was observed in lateral LOC but not ventral LOC. Further, ventral LOC
      voxels were found to be broadly tuned and represent all aspects of stimulus
      similarity, whereas lateral LOC voxels were narrowly tuned and preferentially
      represented the shape of small features rather than their orientation within the
      shape. The results, indicating a coarse spatial coding of shape features in
      lateral LOC and a more focused coding of the entire shape space within ventral
      LOC, may be related to hierarchical models of object processing.

PMID- 19176638
TI  - Glutamatergic inhibition in sensory neocortex.
AB  - In the mammalian brain, glutamate and gamma-aminobutyric acid are considered
      major excitatory and inhibitory neurotransmitters, respectively. However, we have
      found evidence that glutamate can also act as a postsynaptic inhibitory
      neurotransmitter in layer 4 of the neocortex. Using whole-cell recordings from
      layer 4 neurons in slice preparations from the mouse visual, auditory, and
      somatosensory cortices, we found that metabotropic glutamate receptor (mGluR)
      agonists (ACPD, APDC, and DCG IV) elicit a robust, long-lasting hyperpolarization
      that is abolished by the group II mGluR antagonist, MCCG. This response largely
      involves a K(+) conductance mediated by G-protein activity and GIRK channels.
      Furthermore, electrical and photostimulation of the intracortical inputs to layer
      4 elicits a similar hyperpolarization that is blocked by group II mGluR
      antagonists. This novel inhibition mediated by group II mGluRs may be an
      unappreciated mechanism for refining cortical receptive fields in layer 4 and may
      enable synaptic gain control during periods of high activity.

PMID- 19176639
TI  - Associative motor cortex plasticity: direct evidence in humans.
AB  - Previous studies have shown that paired associative stimulation (PAS) protocol,
      in which peripheral nerve stimuli are followed by transcranial magnetic
      stimulation (TMS) of the motor cortex at intervals that produce an approximately
      synchronous activation of cortical networks, enhances the amplitude of motor
      evoked potentials (MEPs) evoked by cortical stimulation. Indirect data support
      the hypothesis that the enhancement of MEPs produced by PAS involves long-term
      potentiation like changes in cortical synapses. The aim of present paper was to
      investigate the central nervous system level at which PAS produces its effects.
      We recorded corticospinal descending volleys evoked by single pulse TMS of the
      motor cortex before and after PAS in 4 conscious subjects who had an electrode
      implanted in the cervical epidural space for the control of pain. The descending
      volleys evoked by TMS represent postsynaptic activity of corticospinal neurones
      that can provide indirect information about the effectiveness of synaptic inputs
      to these neurones. PAS significantly enhanced the amplitude of later descending
      waves, whereas the earliest descending wave was not significantly modified by
      PAS. The present results show that PAS may increase the amplitude of later
      corticospinal volleys, consistent with a cortical origin of the effect of PAS.

PMID- 19176640
TI  - BRG1 and LKB1: tales of two tumor suppressor genes on chromosome 19p and lung
      cancer.
AB  - Losses of heterozygosity (LOH) of the short arm of chromosome 19 are frequent in
      lung cancer, suggesting that one or more tumor suppressor genes are present in
      this region. The LKB1 gene, also called STK11, is somatically inactivated through
      point mutations and large deletions in lung tumors, demonstrating that LKB1 is a
      target of the LOH of this chromosomal arm. Data from several independent groups
      have provided information about the profiles of lung tumors with LKB1
      inactivation and it is generally agreed that this alteration strongly
      predominates in non-small cell lung cancer, in particular adenocarcinomas, in
      smokers. The LKB1 protein has serine-threonine kinase activity and is involved in
      the regulation of the cell energetic checkpoint through the phosphorylation and
      activation of adenosine monophosphate-dependent kinase (AMPK). LKB1 is also
      involved in other processes such as cell polarization, probably through
      substrates other than AMPK. Interestingly, another gene on chromosome 19p, BRG1,
      encoding a component of the SWI/SNF chromatin-remodeling complex, has emerged as
      a tumor suppressor gene that is altered in lung tumors. Similar to LKB1, BRG1 is
      somatically inactivated by point mutations or large deletions in lung tumors
      featuring LOH of chromosome 19p. These observations suggest an important role for
      BRG1 in lung cancer and highlight the need to further our understanding of the
      function of Brahma/SWI2-related gene 1 (BRG1) in cancer. Finally, simultaneous
      mutations at LKB1 and BRG1 are common in lung cancer cells, which exemplifies how
      a single event, LOH of chromosome 19p in this instance, targets two different
      tumor suppressors.

PMID- 19176641
TI  - ATP-sensitive potassium channels control glioma cells proliferation by regulating
      ERK activity.
AB  - Ion channels are found in a variety of cancer cells and necessary for cell cycle
      and cell proliferation. The roles of K(+) channels in the process are, however,
      poorly understood. In the present study, we report that adenosine triphosphate
      (ATP)-sensitive potassium channel activity plays a critical role in the
      proliferation of glioma cells. The expression of K(ATP) channels in glioma
      tissues was greatly increased than that in normal tissues. Treatment of glioma
      cells with tolbutamide, K(ATP) channels inhibitor, suppressed the proliferation
      of glioma cells and blocked glioma cell cycle in G(0)/G(1) phase. Similarly,
      downregulation of K(ATP) channels by small interfering RNA (siRNA) inhibited
      glioma cell proliferation. On the other hand, K(ATP) channels agonist diazoxide
      and overexpression of K(ATP) channels promoted the proliferation of glioma cells.
      Moreover, inhibiting K(ATP) channels slowed the formation of tumor in nude mice
      generated by injection of glioma cells. Whereas activating K(ATP) channels
      promoted development of tumor in vivo. The effect of K(ATP) channels activity on
      glioma cells proliferation is mediated by extracellular signal-regulated kinase
      (ERK) activation. We found that activating K(ATP) channel triggered ERK
      activation and inhibiting K(ATP) channel depressed ERK activation. U-0126, the
      mitogen-activated protein kinase kinase (MAPK kinase) inhibitors blocked ERK
      activation and cell proliferation induced by diazoxide. Furthermore,
      constitutively activated MEK plasmids transfection reversed the inhibitory
      effects of tolbutamide on glioma proliferation, lending further support for a
      role of ERK in mediating this process. Our results suggest that K(ATP) channels
      control glioma cell proliferation via regulating ERK pathway. We concluded that
      K(ATP) channels are important in pathological cell proliferation and open a
      promising pathway for novel targeted therapies.

PMID- 19176642
TI  - Salivary steroid assays - research or routine?
AB  - Salivary concentrations of unconjugated steroids reflect those for free steroids
      in serum although concentrations may differ because of salivary gland metabolism.
      Samples for salivary steroid analysis are stable for up to 7 days at room
      temperature, one month or more at 4 degrees C and three months or more at -20
      degrees C. When assessed against strict criteria, the evidence shows that
      salivary cortisol in evening samples or following dexamethasone suppression
      provides a reliable and effective screen for Cushing's syndrome. Sequential
      salivary cortisol measurements are also extremely helpful for the investigation
      of suspected cyclical Cushing's syndrome. There is potential for the
      identification of adrenal insufficiency when used with Synacthen stimulation.
      Salivary 17-hydroxyprogesterone and androstenedione assays are valued as non
      invasive tests for the home-monitoring of hydrocortisone replacement therapy in
      patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
      The diagnostic value of salivary oestradiol, progesterone, testosterone,
      dehydroepiandrosterone and aldosterone testing is compromised by rapid
      fluctuations in salivary concentrations of these steroids. Multiple samples are
      required to obtain reliable information, and at present the introduction of these
      assays into routine laboratory testing is not justified.

PMID- 19176643
TI  - Simultaneous measurement of urinary metanephrines and catecholamines by liquid
      chromatography with tandem mass spectrometric detection.
AB  - BACKGROUND: The measurement of catecholamines and metanephrines in urine is an
      important diagnostic test in biochemical screening for phaeochromocytoma. Tandem
      mass spectrometry (MSMS) has the potential to be used in a profiling method for
      simultaneous assay of these analytes. METHODS: Optimal conditions were
      established for the MSMS detection of catecholamines (noradrenalin, adrenalin and
      dopamine) and metanephrines (normetanephrine and metanephrine), including
      commercially available isotopically labelled compounds for use as internal
      standards. Chromatographic separation of all five polar biogenic amines was
      achieved under solvent conditions that were compatible with MSMS and multiple
      reaction monitoring. Several types of solid-phase extraction cartridge were used
      to investigate clean-up conditions for urine, and acid-hydrolysates of urine,
      prior to LC-MSMS. RESULTS: Total catecholamines and metanephrines from acid
      hydrolysed urines, or free catecholamines and free metanephrines from native
      urines, were complexed with diphenyl-boronate and recovered in high yield from
      polymer cartridges after elution with formic acid. Direct injection of eluates
      into the LC-MSMS system allowed quantitation of catecholamines and metanephrines
      with a run time of 6 min per sample. Biogenic amine concentrations for patient
      urines and quality assurance programme samples, and assay imprecision, were
      similar to values obtained with high-performance liquid chromatography methods,
      which used electrochemical detection. In normal urines, the ratio of free to
      total catecholamines was around three-fold higher than the ratio of free to total
      metanephrines. CONCLUSION: The assay of urinary catecholamines and metanephrines
      can be achieved simultaneously using one LC-MSMS method, which is rapid and
      reduces labour and consumable costs for routine application.

PMID- 19176644
TI  - Appropriateness of the National Academy of Clinical Biochemistry recommendation
      of repeating HbA1c analysis for extreme results in clinical practice.
AB  - BACKGROUND: The National Academy of Clinical Biochemistry (NACB) recommends that
      the presence of a variant or modified haemoglobin be considered when any HbA1c
      result is below the lower limit of the reference interval or >or=15%. In those
      instances where a variant haemoglobin is suspected, repeat measurement using an
      alternative method is the usual course of action. In the present study, we
      undertook to determine the impact of this guideline on our identification of
      variant and modified haemoglobins. METHODS: All requests for HbA1c estimation
      received over a 32-month period, and which gave a result of <4% or >15% were re
      analysed by a different method and the results compared. RESULTS: Over the 32
      month period, 94 samples with a HbA1c result of <4% or >or=15% were identified.
      Of these, 80 were re-analysed using a different method. No chromatographic
      abnormalities were seen and there were no significant differences between the
      results obtained using the two methods. CONCLUSIONS: No variant or modified
      haemoglobins were identified in this study and this observation is likely to be
      representative of the ethnic makeup of our patient population. On the basis of
      this finding, we recommend that laboratories consider local factors when deciding
      whether to comply with the NACB guidelines.

PMID- 19176645
TI  - Incorrect use of ratios in commercial assay kit instructions.

PMID- 19176646
TI  - Unique expression pattern of the EMT markers Snail, Twist and E-cadherin in
      benign and malignant parathyroid neoplasia.
AB  - BACKGROUND: Epithelial and mesenchymal transitions (EMT) are essential for
      embryonic development and progression of non-invasive tumor cells into malignant,
      metastatic carcinomas. During embryogenesis, the parathyroid glands develop from
      pharyngeal pouches and migrate to their final destinations, densely enclosed by
      mesenchymal neural crest cells. In this study, we examined the expression of the
      EMT markers Snail, Twist and E-cadherin in normal parathyroid glands and benign
      and malignant parathyroid diseases. METHODS: Using immunohistochemistry, we
      compared expression of E-cadherin, Snail and Twist in 25 patients with
      parathyroid adenoma, 25 patients with parathyroid hyperplasia, and nine patients
      with parathyroid cancer with normal parathyroid glands. RESULTS: Normal
      parathyroid glands, parathyroid adenomas, and parathyroid hyperplasias showed a
      typical membranous E-cadherin staining pattern. Expression of Snail was found in
      22/25 parathyroid adenomas and in all parathyroid hyperplasias. Twist was
      expressed in 22/25 of parathyroid adenomas and in 20/25 parathyroid hyperplasias.
      Snail and Twist positive cells were homogeneously distributed throughout the
      gland. However, in all nine parathyroid carcinomas, membranous E-cadherin
      staining was lost. In addition, the expression pattern of Snail and Twist was
      changed and mostly limited to the invasive front of cancer tissue samples.
      CONCLUSION: Expression of Snail and Twist at the invasive front and consecutive
      loss of E-cadherin in parathyroid carcinomas suggests a key role of EMT in the
      tumorigenesis of this cancer. The unique expression pattern could help to
      distinguish between an adenoma and a non-metastatic carcinoma. Loss of E-cadherin
      and change of the expression pattern of Snail and Twist together should result in
      an en bloc resection or a close follow-up.

PMID- 19176647
TI  - Fibrous dysplasia in a Hong Kong community: the clinical and radiological
      features and outcomes of treatment.
AB  - OBJECTIVES: To evaluate the principal clinical and radiological features of a
      consecutive series of cases of fibrous dysplasia (FD) affecting a Hong Kong
      Chinese community and to determine their outcome by follow-up. METHODS: All cases
      were accompanied by appropriate radiography and were histopathologically
      confirmed as fibro-osseous lesions. RESULTS: The clinical and radiological
      presentations, differential diagnoses and outcomes of follow-up of 21 consecutive
      FD cases were reviewed. Females were slightly more frequently affected, but there
      was no gender predilection for either jaw. The mean age at first presentation was
      25 years, which upon adjustment for prior awareness fell to 21 years. The main
      symptom was swelling (including enlargement of the jaw). The maxilla and mandible
      were affected in 9 and 13 cases, respectively; both jaws were affected in 1 case.
      One case was of McCune-Albright syndrome. The sole provisional diagnosis for all
      lesions was FD; most lesions affected all or almost half the affected jaw. 17
      patients were followed-up for a mean of 9 years. CONCLUSIONS: This very detailed
      consecutive series followed up over many years, in which a number of cases
      recurred or were reactivated in adulthood, firmly dispells the notion that FD is
      a simple hamartoma in all cases. This community was quite amenable to really long
      term follow-up.

PMID- 19176648
TI  - In vivo study of pixel grey-measurement in digital subtraction radiography for
      monitoring caries remineralization.
AB  - OBJECTIVES: The aim of this study was to evaluate the performance of a
      quantitative method, based on pixel grey value measurements, for monitoring
      caries remineralization. METHODS: Proximal radiographs of 11 patients (61 enamel
      caries lesions) were taken both before and after a 2 month remineralization
      protocol. Radiographs were digitized and for each area a follow-up image was
      subtracted from a baseline image. A quantitative analysis was undertaken using
      ImageTool software (University of Texas Health Science Center, San Antonio, TX).
      For each caries lesion diagnosed, a mean pixel value was obtained in digital
      subtraction radiographs (SR) using a scale ranging from 0-255 grey values. To
      identify caries status after the remineralization protocol, a subjective analysis
      of SR was undertaken by 6 radiologists who graded the lesions as demineralized (n
      = 10), unchanged (n = 34) or remineralized (n = 17). RESULTS: There was a
      statistically significant difference between the mean pixel values for
      demineralized (112.1+/-14.4), unchanged (127.3+/-12.3) and remineralized (137.5+/
      13.8) lesions. CONCLUSIONS: It was concluded that the status of proximal caries
      lesions after remineralization therapy can be assessed by pixel grey measurements
      in SR and may constitute a suitable complementary method for monitoring the
      results of remineralization protocol in clinical practice.

PMID- 19176649
TI  - Absorbed and effective doses from cone beam volumetric imaging for implant
      planning.
AB  - OBJECTIVES: Volumetric CT using a cone beam has been developed by several
      manufacturers for dentomaxillofacial imaging. The purpose of this study was to
      measure doses for implant planning with cone beam volumetric imaging (CBVI) in
      comparison with conventional multidetector CT (MDCT). METHODS: The two CBVI
      systems used were a 3D Accuitomo (J. Morita), including an image-intensifier type
      (II) and a flat-panel type (FPD), and a CB MercuRay (Hitachi). The 3D Accuitomo
      operated at 80 kV, 5 mA and 18 s. The CB MercuRay operated at 120 kV, 15 mA, 9.8
      s. The MDCT used was a HiSpeed QX/i (GE), operated at 120 kV, 100 mA and 0.7 s,
      and its scan length was 77 mm for both jaws. Measurement of the absorbed tissue
      and organ doses was performed with an Alderson phantom, embedding the
      radiophotoluminescence glass dosemeter into the organs/tissues. The values
      obtained were converted into the absorbed dose. The effective dose as defined by
      the International Commission on Radiological Protection was then calculated.
      RESULTS: The absorbed doses of the 3D Accuitomo of the organs in the primary beam
      ranged from 1-5 mGy, and were several to ten times lower than other doses. The
      effective dose of the 3D Accuitomo ranged from 18 muSv to 66 muSv, and was an
      order of magnitude smaller than the others. In conclusion, these results show
      that the dose in the 3D Accuitomo is lower than the CB MercuRay and much less
      than MDCT.

PMID- 19176650
TI  - Mandibular cortical index evaluation in masked and unmasked panoramic
      radiographs.
AB  - OBJECTIVES: The first aim of this study was to evaluate intra- and interobserver
      agreement in evaluating the mandibular cortical index (MCI) in masked and
      unmasked panoramic radiographs. The second aim was to evaluate the effect of
      previous experience of MCI classification on the observers' performance. METHODS:
      Three observers separately evaluated MCI, twice in masked and twice in unmasked
      panoramic radiographs, with 2 week intervals. The observations were repeated more
      than 9 months later. The second and third observers were inexperienced in
      evaluating MCI. Weighted kappa statistics were used to evaluate the inter- and
      intraobserver agreement. RESULTS: In the first session of the study, the kappa
      values for intraobserver agreements in masked panoramic radiographs were between
      0.565 and 0.789; in unmasked panoramic radiographs, they were between 0.420 and
      0.732. The kappa values for interobserver agreement were between 0.131 and 0.392
      in masked radiographs and between 0.043 and 0.225 in unmasked radiographs. In the
      second session of the study, the kappa values for intraobserver agreements in
      masked panoramic radiographs were between 0.586 and 0.786. The kappa values for
      intraobserver agreements in unmasked panoramic radiographs were between 0.558 and
      0.781. The kappa values for interobserver agreement were between 0.146 and 0.510
      in masked radiographs and between 0.174 and 0.568 in unmasked radiographs.
      CONCLUSIONS: Masking has no effect on the evaluation of panoramic radiographs for
      MCI. Previous experience causes higher intraobserver agreement. Intra- and
      interobserver agreement increases along with the increased experience in MCI
      evaluations.

PMID- 19176651
TI  - Is it true that the radiation dose to which patients are exposed has decreased
      with modern radiographic films?
AB  - OBJECTIVES: To determine whether the radiation dose administered to patients has
      decreased with new radiographic films and digital imaging systems. METHODS: A
      total of 10 171 official reports on radiological practice in dental surgeries
      (covering the years 1996-2003) from 16 Spanish autonomous regions were studied,
      analysing the type of film used, the exposure times and the radiation doses
      administered in each dental clinic for four different teeth: upper molar, lower
      molar, upper incisor and lower incisor. RESULTS: The Agfa Dentus M2 radiographic
      film needed the longest exposure times for all of the teeth (0.6 s, 0.5 s, 0.4 s
      and 0.4 s, respectively) followed in decreasing order by Ultraspeed, Insight,
      Ektaspeed and the digital systems, the decrease with respect to the first
      reaching as much as 60%. Regarding the dose administered, Agfa Dentus M2 used the
      highest dose (3.1 mGy) followed by Ultraspeed (2.7 mGy), Insight (2.2 mGy),
      Ektaspeed (2.2 mGy) and, finally, the digital systems (1.1 mGy). Statistical
      analysis showed significant differences between the doses administered for the
      digital systems with respect to the radiographic films (P < 0.001) and with
      respect to manual or automatic processing (P < 0.001). However, there were no
      significant differences in dose between the different types of films themselves,
      or between the radiographic developing processes themselves (manual and
      automatic). CONCLUSION: Not even the use of the most sensitive of modern films
      has brought about a reduction of the dose administered to patients in Spain. Only
      digital systems, it seems, will bring about reduction in this dose.

PMID- 19176652
TI  - The status of oral and maxillofacial radiology worldwide in 2007.
AB  - The status of oral and maxillofacial radiology in other countries is often of
      importance when making an application for specialty recognition. This information
      has not previously been readily available. This paper presents the results of a
      survey to determine the status of oral and maxillofacial radiology worldwide in
      2007.

PMID- 19176653
TI  - Volumetric tomography - a new tomographic technique for panoramic units.
AB  - OBJECTIVES: To introduce a new three-dimensional dental imaging technique named
      volumetric tomography (VT). METHODS: The new VT imaging method utilizes an
      iterative frequency-based reconstruction technique. With iterative algorithms
      each voxel value is defined multiple times during reconstruction. Computation
      time is therefore relatively lengthy. However, multicore processors and graphic
      board programming reduce the reconstruction time, making it possible to utilize
      this iterative reconstruction technique in clinical practice. The new VT
      technique is an add-on to a standard panoramic unit (Orthopantomograph OP 200 D;
      Instrumentarium Oy, Tuusula, Finland). Unit enhancements include a device for
      patient positioning and additional software. Preliminary clinical examinations
      have been performed. RESULTS: Examinations demonstrated that the new VT technique
      gives satisfactory volumetric patient data from which tomographs may be derived
      for different clinical applications. CONCLUSIONS: The new VT method may be
      employed when tomographic examinations are required for dental clinical work.

PMID- 19176654
TI  - A rare case of a glass foreign body in the parapharyngeal space: pre-operative
      assessment by contrast-enhanced CT and three-dimensional CT images.
AB  - The parapharyngeal space is an infrequent area for foreign bodies to lodge.
      However, the presence of trauma or inflammation near or within the space is
      dangerous because of its anatomical proximity to the bifurcation of the maxillary
      artery, carotid artery and jugular vein. We encountered a rare case, when a glass
      flask burst, in which intraparotid damage to the facial nerve was seen, as well
      as a glass foreign body lodged in the parapharyngeal space close to the above
      named great vessels. We emphasise the usefulness of contrast-enhanced CT and
      three-dimensional CT images for pre-operative evaluation of the locational
      relationship between the foreign body and great vessels in the parapharyngeal
      space.

PMID- 19176655
TI  - A misdiagnosis: duplication of the external auditory canal.
AB  - We present imaging and clinical findings of a case with a duplicated external
      auditory canal, which led to misdiagnosis secondary to lipomatous content on
      imaging studies prior to surgery. It is a very rare congenital anomaly. This
      entity is usually misdiagnosed not only clinically but also radiologically. This
      leads to a delay and failure in diagnosis and treatment. To the best of our
      knowledge, herein is the first case report of the duplication of the external
      auditory canal presenting with dominant lipomatous imaging features. In this
      report, we aim to draw attention to the atypical presentation.

PMID- 19176656
TI  - Bilateral submandibular gland aplasia with clinico-radiological mass due to
      prolapsing sublingual salivary tissue through mylohyoid boutonniere: a case
      report and review.
AB  - Aplasia of major salivary glands is very rare. Compensatory hypertrophy of the
      rest of the glands can result in clinico-radiological masses. We present a report
      of a rare case of non-syndromic bilateral submandibular gland aplasia with
      hypertrophied sublingual salivary tissue, the latter herniating through mylohyoid
      boutonniere to present as a palpable mass on the left side with corresponding CT
      findings. Multiplanar evaluation is emphasised by utilizing multidetector CT.

PMID- 19176657
TI  - Diagnostic features of the paradental cyst and report of a case.

PMID- 19176658
TI  - An unusual cause of back pain.

PMID- 19176660
TI  - A woman with ataxia.

PMID- 19176662
TI  - One laptop per primary care worker in developing countries.

PMID- 19176663
TI  - One Laptop per Child and health. Noblesse oblige.

PMID- 19176664
TI  - Happiness networks. What about social politics?

PMID- 19176665
TI  - Happiness networks. Know your friends.

PMID- 19176671
TI  - Caffeine in pregnancy. Food Standard Agency's advice on caffeine.

PMID- 19176672
TI  - Cut caffeine in pregnancy?

PMID- 19176673
TI  - The NHS carbon reduction strategy.

PMID- 19176674
TI  - A constitution for the NHS.

PMID- 19176676
TI  - More treatment in surgeries and at home will help cut NHS carbon footprint.

PMID- 19176677
TI  - Health Technology Assessment. NICE goes global.

PMID- 19176682
TI  - Borderline and antisocial personality disorders: summary of NICE guidance.

PMID- 19176683
TI  - Exploratory study of relationship between hospitalized heart failure patients and
      chronic renal replacement therapy.
AB  - BACKGROUND: Chronic kidney disease (CKD) is common in heart failure (HF) and is
      associated with poor outcomes. Renal replacement therapy (RRT) may be deferred
      over concerns regarding tolerability and outcomes in HF. Our objectives were to
      ascertain the incidence of RRT, changes in RRT incidence over time and the
      association between RRT and survival in hospitalized HF patients. METHODS: A
      retrospective cohort study of consecutive hospitalized HF patients was performed
      at a single centre from 1987 to 2002 with RRT data from the United States Renal
      Data System. RESULTS: Of 6276 HF patients without RRT on admission, 304 commenced
      chronic (>or=3 months) RRT (280 dialysis only; 24 transplant) at a median of 475
      days after dismissal. Overall incidence was 1.6% per year. Risk-adjusted
      incidence increased over time and was similar in those with preserved or reduced
      (<50%) ejection fraction. RRT patients were younger but had worse renal function
      and anaemia, and more diabetes, hypertension and coronary disease. Unadjusted
      survival was worse in the RRT group. However, risk-adjusted survival was similar
      in RRT and non-RRT groups (HR = 1.11, 95% CI 0.94-1.29, P > 0.05). CONCLUSIONS:
      Our data show that although RRT is increasingly used in HF patients, the impact
      on risk-adjusted mortality remains to be established. Further studies should
      focus on defining the appropriate clinical settings in which RRT should be used
      in HF, the timing and type of RRT and whether RRT can improve specific outcomes.

PMID- 19176684
TI  - The effect of rabbit anti-thymocyte globulin induction therapy on regulatory T
      cells in kidney transplant patients.
AB  - BACKGROUND: Prevention of alloreactivity by rabbit anti-thymocyte globulins
      (rATG) may not only result from immunodepletion but also from the induction of T
      cells that control allogeneic immune responses. In the present prospective and
      controlled study, we investigated the effect of rATG on the frequency, function
      and phenotype of peripheral immunoregulatory CD4+ T cells in kidney transplant
      (KTx) patients. METHODS: After transplantation, 16 patients received ATG
      induction therapy and triple therapy consisting of tacrolimus, MMF and steroids.
      The control group (n = 18) received triple therapy only. By flow cytometry, T
      cells were analysed for CD25, FoxP3, CD127, CD45RO and CCR7. To study their
      suppressive capacities, CD25bright T cells were co-cultured with CD25(-/dim)
      effector T cells (Teff) in mixed lymphocyte reactions (MLR), stimulated with
      donor and third party (3P) antigens. RESULTS: Pre-transplant levels of
      FoxP3+CD127(-/low) T cells were 6% of CD4+ T cells. One week post-ATG treatment,
      no measurable numbers of regulatory T cells were present (P < 0.01). After 4
      weeks, the cell numbers of CD4+FoxP3+CD127(-/low) T cells slowly reappeared and
      thereafter remained low (P < 0.01). At 14 weeks, a significant shift towards the
      CD45RO+CCR7+ (central memory) phenotype within CD4+FoxP3+ T cells was observed (P
      < 0.01). At 26 weeks, the proliferative alloresponses of the PBMC and CD25(-/dim)
      Teff profoundly decreased compared to pre-transplant (P = 0.01 and P = 0.02
      respectively), while the regulatory capacity of the CD25bright T cells, of which
      90% consisted of FoxP3+CD127(-/low) T cells, remained unaffected. The CD25bright
      T cells suppressed the anti-donor (94%) and 3P responses (93%). CONCLUSION: Our
      findings show that rATG therapy does not spare peripheral immunoregulatory T
      cells in vivo, but after regeneration preserves their suppressive activity.

PMID- 19176686
TI  - Alpha-tocopherol supplementation decreases electronegative low-density
      lipoprotein concentration [LDL(-)] in haemodialysis patients.
AB  - BACKGROUND: Oxidative stress is a significant contributor to cardiovascular
      diseases (CVD) in haemodialysis (HD) patients, predisposing to the generation of
      oxidized low-density lipoprotein (oxLDL) or electronegatively charged LDL
      subfraction. Antioxidant therapy such as alpha-tocopherol acts as a scavenger of
      lipid peroxyl radicals attenuating the oxidative stress, which decreases the
      formation of oxLDL. The present study was designed to investigate the influence
      of the alpha-tocopherol supplementation on the concentration of electronegative
      low-density lipoprotein [LDL(-)], a minimally oxidized LDL, which we have
      previously described to be high in HD patients. METHODS: Blood samples were
      collected before and after 120 days of supplementation by alpha-tocopherol (400
      UI/day) in 19 stable HD patients (50 +/- 7.8 years; 9 males). The concentrations
      of LDL(-) in blood plasma [using an anti-LDL- human monoclonal antibody (mAb)]
      and the anti-LDL(-) IgG auto-antibodies were determined by ELISA. Calculation of
      body mass index (BMI) and measurements of waist circumference (WC), triceps skin
      folds (TSF) and arm muscle area (AMA) were performed. RESULTS: The plasma alpha
      tocopherol levels increased from 7.9 microM (0.32-18.4) to 14.2 microM (1.22
      23.8) after the supplementation (P = 0.02). The mean concentration of LDL(-) was
      reduced from 570.9 microg/mL (225.6-1241.0) to 169.1 microg/mL (63.6-621.1) (P <
      0.001). The anti-LDL(-) IgG auto-antibodies did not change significantly after
      the supplementation. The alpha-tocopherol supplementation also reduced the total
      cholesterol and LDL-C levels in these patients, from 176 +/- 42.3 mg/dL to 120 +/
      35.7 mg/dL (P < 0.05) and 115.5 +/- 21.4 mg/dL to 98.5 +/- 23.01 mg/dL (P <
      0.001), respectively. CONCLUSION: The oral administration of alpha-tocopherol in
      HD patients resulted in a significant decrease in the LDL(-), total cholesterol
      and LDL-C levels. This effect may favour a reduction in cardiovascular risk in
      these patients, but a larger study is required to confirm an effect in this
      clinical setting.

PMID- 19176685
TI  - Protocol adherence and the ability to achieve target haemoglobin levels in
      haemodialysis patients.
AB  - BACKGROUND: Anemia management remains complicated in patients with endstage renal
      disease on hemodialysis. We wished to evaluate the effect of protocol adherence
      to EPO and intravenous iron dosing on achieving the desired range of hemoglobin
      levels. METHODS: A cohort of hemodialysis patients was studied to evaluate the
      rate of adherence to EPO and iron dosing protocols over a 5 month period. A
      database was completed to evaluate all known comorbidities, demographic factors,
      and facility issues that might affect hemoglobin levels. A logistic regression
      model was employed to evaluate the effect of adherence to the anemia protocols on
      the probability of achieving a hemoglobin level below, within or above the
      targeted range of 11-12.5 g/dl. RESULTS: Among 2114 patients, we found that
      adherence to both the EPO and iron dosing protocol resulted in the greatest
      probability of achieving the target hemoglobin range (56 +/- 5% in anemia
      protocol adherent patients versus 42 +/- 7% in non adherent patients). This was
      predominantly due to a lowered risk of having above target hemoglobin levels
      rather than below. The use of the anemia protocols was associated with lower
      rates of hospitalization (9 +/- 0.7 visits/100 months in adherent group vs 15 +/-
      2 in non adherent group) and lower utilization of both EPO and intravenous iron.
      Furthermore, patients in the adherent groups had less variability of their
      hemoglobin levels month by month, at least as judged by standard deviation.
      CONCLUSION: Adherence to anemia protocols, as practiced in the dialysis units
      included in this cohort, may improve hemodialysis patients' ability to achieve
      target hemoglobin levels, and by avoiding above target hemoglobin values, lower
      drug utilization and reduce variability of hemoglobin levels.

PMID- 19176687
TI  - Battle against the renin-angiotensin system: help from an unexpected party.

PMID- 19176688
TI  - Lack of association between TGF-beta-1 genotypes and microalbuminuria in
      essential hypertensive men.
AB  - BACKGROUND: Polymorphisms within the gene for transforming growth factor (TGF)
      beta-1, a pro-fibrogenic cytokine pathophysiologically involved in hypertension
      and hypertensive target damage, might modulate the biological activity of the
      encoded protein. Through that mechanism, they might contribute to
      microalbuminuria, a marker of subclinical renal damage and a correlate of
      systemic inflammation and endothelial dysfunction in hypertension, a possibility
      never before tested. For this reason, we assessed the association of four TGF
      beta-1 polymorphic variants (C-509T, Leu(10)-->Pro, Arg(25)-->Pro, Thr(263)-
      >Ile) with albuminuria in uncomplicated essential hypertensive men, using
      (circulating active + acid-activatable latent) TGF-beta-1 levels as an indirect
      index of their in vivo biological activity. Because of the close
      pathophysiological link of TGF-beta-1 with the renin-angiotensin system, we also
      tested the behaviour of the angiotensin converting enzyme (ACE)
      deletion/insertion (D/I) polymorphism. METHODS: Albuminuria (three overnight
      collections), office and 24-h BP, left ventricular mass index (LVMI), BMI, renal
      function, glucose, lipids, plasma TGF-beta-1 (n = 162, ELISA) were measured in
      222 genetically unrelated, never-treated, uncomplicated Caucasian hypertensive
      men. ACE D/I polymorphisms were analysed by the polymerase chain reaction
      technique or a 5' nuclease assay with further restriction analysis when required.
      RESULTS: Urine albumin levels or microalbuminuria (albuminuria > or =15
      microg/min) did not differ by TGF-beta-1 genotypes, but both parameters were more
      frequent in ACE D/D homozygotes. Plasma TGF-beta-1 was similar across genetic
      backgrounds and was unrelated to albuminuria. Cardiovascular, renal, metabolic
      parameters were homogeneously distributed across genotypes. CONCLUSIONS: In
      contrast to its link with the ACE D/I genotype, microalbuminuria was independent
      of TGF-beta-1 polymorphism in this group of never-treated, uncomplicated
      essential hypertensive men.

PMID- 19176689
TI  - Activation of the AKT/mTOR pathway in autosomal recessive polycystic kidney
      disease (ARPKD).
AB  - BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) [MIM 263200]
      belongs to a group of congenital hepatorenal fibrocystic syndromes and is caused
      by mutations in the PKHD1 gene encoding the multidomain protein
      fibrocystin/polyductin (FPC). The serine-threonine kinase mammalian target of
      rapamycin (mTOR) is one of the most important gate-keepers integrating numerous
      signals related to cell proliferation and growth. Whereas the direct activation
      of mTOR has been shown recently in autosomal-dominant PKD, no data are available
      on the role of mTOR signalling in proliferation and progression of ARPKD.
      METHODS: Formalin-fixed and paraffin-embedded kidney specimens obtained during
      nephrectomy from children with ARPKD (n = 12) were used for immunohistochemical
      investigation of FPC expression (monoclonal antibody (mAb) 18, mAb 5a),
      proliferative activity (Ki-67) and activation of the mTOR pathway. Kidney
      specimens from children (n = 4) who died from causes not associated with kidney
      disease served as controls. For the detection of AKT, mTOR and S6K antibodies
      specifically recognizing the activated (phosphorylated) isoforms of these
      proteins were used. In all patients mutation analysis of the PKHD1 gene was
      performed. RESULTS: In 10 out of 12 patients, we could confirm the diagnosis by
      the identification of PKHD1 mutations. The tubular cyst epithelium of all kidney
      specimens stained strongly positive with the FPC-specific monoclonal antibody
      (mAb) 18 but only very faint signals were obtained with mAb 5a. In contrast,
      healthy kidneys showed rather weak signals with both FPC-specific mAbs,
      indicating dysregulated expression of FPC in our patients. Phosphorylated AKT as
      well as activated mTOR and its down-stream effector S6K were strongly expressed
      in cystic epithelia of all kidney specimens but not in control tissues. No
      association between the activation of this pathway and the proliferative activity
      (Ki-67 expression) was observed. CONCLUSIONS: Our results point to a central role
      of AKT/mTOR signalling in ARPKD and justify further investigations to evaluate
      the therapeutic potential of mTOR inhibitors in ARPKD patients.

PMID- 19176690
TI  - Prevalence of anti-varicella-zoster virus antibodies in French infants under 15
      months of age.
AB  - Varicella is a widespread disease of childhood resulting from primary infection
      with varicella-zoster virus (VZV). The objective of this study was to determine
      the kinetics of the decline of maternal anti-VZV antibodies in French infants
      between birth and the age of 15 months in order to estimate the duration of
      passively acquired maternal anti-VZV immunoglobulin G (IgG). This prospective
      multicenter study was conducted between October 2005 and January 2007 in the
      pediatric wards and/or pediatric emergency units of seven French hospitals
      scattered throughout the country. The level of anti-VZV IgG antibodies in serum
      was measured by a time-resolved fluorescence immunoassay (TRFIA) (the threshold
      considered positive is 150 mIU/ml). A total of 345 infants were included. Seventy
      seven percent of mothers reported a history of varicella. A rapid decline in the
      prevalence of anti-VZV antibodies was observed during the first few months of
      life, with the mean antibody titer decreasing from 536 mIU/ml at birth and
      through 1 month to below the 150-mIU/ml threshold at 3 to 4 months. The half-life
      of passively acquired maternal immunoglobulins was around 6 weeks. Based on a
      large number of subjects, this study clearly demonstrated, for the first time in
      France, high levels of passively acquired maternal antibodies during the neonatal
      period, and it allowed us to estimate the duration of passively acquired maternal
      anti-VZV IgG in French infants. After 4 to 5 months, infants had very low levels
      of maternal anti-VZV IgG, below the 150-mIU/ml cutoff of the VZV IgG TRFIA.

PMID- 19176691
TI  - A DNA vaccine encoding the enterohemorragic Escherichia coli Shiga-like toxin 2
      A2 and B subunits confers protective immunity to Shiga toxin challenge in the
      murine model.
AB  - Production of verocytotoxin or Shiga-like toxin (Stx), particularly Stx2, is the
      basis of hemolytic uremic syndrome, a frequently lethal outcome for subjects
      infected with Stx2-producing enterohemorrhagic Escherichia coli (EHEC) strains.
      The toxin is formed by a single A subunit, which promotes protein synthesis
      inhibition in eukaryotic cells, and five B subunits, which bind to
      globotriaosylceramide at the surface of host cells. Host enzymes cleave the A
      subunit into the A(1) peptide, endowed with N-glycosidase activity to the 28S
      rRNA, and the A(2) peptide, which confers stability to the B pentamer. We report
      the construction of a DNA vaccine (pStx2DeltaAB) that expresses a nontoxic Stx2
      mutated form consisting of the last 32 amino acids of the A(2) sequence and the
      complete B subunit as two nonfused polypeptides. Immunization trials carried out
      with the DNA vaccine in BALB/c mice, alone or in combination with another DNA
      vaccine encoding granulocyte-macrophage colony-stimulating factor, resulted in
      systemic Stx-specific antibody responses targeting both A and B subunits of the
      native Stx2. Moreover, anti-Stx2 antibodies raised in mice immunized with
      pStx2DeltaAB showed toxin neutralization activity in vitro and, more importantly,
      conferred partial protection to Stx2 challenge in vivo. The present vector
      represents the second DNA vaccine so far reported to induce protective immunity
      to Stx2 and may contribute, either alone or in combination with other procedures,
      to the development of prophylactic or therapeutic interventions aiming to
      ameliorate EHEC infection-associated sequelae.

PMID- 19176692
TI  - Francisella tularensis infection-derived monoclonal antibodies provide detection,
      protection, and therapy.
AB  - Francisella tularensis is the causative agent of tularemia and a potential agent
      of biowarfare. As an easily transmissible infectious agent, rapid detection and
      treatment are necessary to provide a positive clinical outcome. As an agent of
      biowarfare, there is an additional need to prevent infection. We made monoclonal
      antibodies to the F. tularensis subsp. holarctica live vaccine strain (F.
      tularensis LVS) by infecting mice with a sublethal dose of bacteria and,
      following recovery, by boosting the mice with sonicated organisms. The response
      to the initial and primary infection was restricted to immunoglobulin M antibody
      directed solely against lipopolysaccharide (LPS). After boosting with sonicated
      organisms, the specificity repertoire broadened against protein antigens,
      including DnaK, LpnA, FopA, bacterioferritin, the 50S ribosomal protein L7/L12,
      and metabolic enzymes. These monoclonal antibodies detect F. tularensis LVS by
      routine immunoassays, including enzyme-linked immunosorbent assay, Western blot
      analysis, and immunofluorescence. The ability of the antibodies to protect mice
      from intradermal infection, both prophylactically and therapeutically, was
      examined. An antibody to LPS which provides complete protection from infection
      with F. tularensis LVS and partial protection from infection with F. tularensis
      subsp. tularensis strain SchuS4 was identified. There was no bacteremia and
      reduced organ burden within the first 24 h when mice were protected from F.
      tularensis LVS infection with the anti-LPS antibody. No antibody that provided
      complete protection when administered therapeutically was identified; however,
      passive transfer of antibodies against LPS, FopA, and LpnA resulted in 40 to 50%
      survival of mice infected with F. tularensis LVS.

PMID- 19176693
TI  - Immune responses and protection against experimental challenge after vaccination
      of bison with Brucella abortus strain RB51 or RB51 overexpressing superoxide
      dismutase and glycosyltransferase genes.
AB  - Vaccination is a tool that could be beneficial in managing the high prevalence of
      brucellosis in free-ranging bison in Yellowstone National Park. In this study, we
      characterized immunologic responses and protection against experimental challenge
      after vaccination of bison with Brucella abortus strain RB51 (RB51) or a
      recombinant RB51 strain overexpressing superoxide dismutase (sodC) and
      glycosyltransferase (wboA) genes (RB51+sodC,wboA). Bison were vaccinated with
      saline only or with 4.6 x 10(10) CFU of RB51 or 7.4 x 10(10) CFU of
      RB51+sodC,wboA (n = eight animals/treatment). Bison vaccinated with RB51 or
      RB51+sodC,wboA had greater (P < 0.05) antibody responses, proliferative
      responses, and production of gamma interferon to RB51 after vaccination than did
      nonvaccinates. However, bison vaccinated with RB51+sodC,wboA cleared the vaccine
      strain from draining lymph nodes faster than bison vaccinated with the parental
      RB51 strain. Immunologic responses of bison vaccinated with RB51+sodC,wboA were
      similar to responses of bison vaccinated with RB51. Pregnant bison were
      intraconjunctivally challenged in midgestation with 10(7) CFU of B. abortus
      strain 2308. Bison vaccinated with RB51, but not RB51+sodC,wboA vaccinates, had
      greater protection from abortion, fetal/uterine, mammary, or maternal infection
      than nonvaccinates. Our data suggest that the RB51+sodC,wboA strain is less
      efficacious as a calfhood vaccine for bison than the parental RB51 strain. Our
      data also suggest that the RB51 vaccine is a currently available management tool
      that could be utilized to help reduce brucellosis in free-ranging bison.

PMID- 19176694
TI  - From genome-based in silico predictions to ex vivo verification of leprosy
      diagnosis.
AB  - The detection of hundreds of thousands of new cases of leprosy every year
      suggests that transmission of Mycobacterium leprae infection still continues.
      Unfortunately, tools for identification of asymptomatic disease and/or early
      stage M. leprae infection (likely sources of transmission) are lacking. The
      recent identification of M. leprae-unique genes has allowed the analysis of human
      T-cell responses to novel M. leprae antigens. Antigens with the most-promising
      diagnostic potential were tested for their ability to induce cytokine secretion
      by using peripheral blood mononuclear cells from leprosy patients and controls in
      five different areas where leprosy is endemic; 246 individuals from Brazil,
      Nepal, Bangladesh, Pakistan, and Ethiopia were analyzed for gamma interferon
      responses to five recombinant proteins (ML1989, ML1990, ML2283, ML2346, and
      ML2567) and 22 synthetic peptides. Of these, the M. leprae-unique protein ML1989
      was the most frequently recognized and ML2283 the most specific for M. leprae
      infection/exposure, as only a limited number of tuberculosis patients responded
      to this antigen. However, all proteins were recognized by a significant number of
      controls in areas of endemicity. T-cell responses correlated with in vitro
      response to M. leprae, suggesting that healthy controls in areas where leprosy is
      endemic are exposed to M. leprae. Importantly, 50% of the healthy household
      contacts and 59% of the controls in areas of endemicity had no detectable
      immunoglobulin M antibodies to M. leprae-specific PGL-I but responded in T-cell
      assays to >or=1 M. leprae protein. T-cell responses specific for leprosy patients
      and healthy household contacts were observed for ML2283- and ML0126-derived
      peptides, indicating that M. leprae peptides hold potential as diagnostic tools.
      Future work should concentrate on the development of a sensitive and field
      friendly assay and identification of additional peptides and proteins that can
      induce M. leprae-specific T-cell responses.

PMID- 19176695
TI  - Parietal epithelial cells regenerate podocytes.

PMID- 19176696
TI  - Phosphorus and survival: key questions that need answers.

PMID- 19176697
TI  - Proteomic portrayal of transplant pathologies.

PMID- 19176698
TI  - Plasmin and sodium retention in nephrotic syndrome.

PMID- 19176699
TI  - Soluble thrombomodulin protects ischemic kidneys.
AB  - Altered coagulation and inflammation contribute to the pathogenesis of ischemic
      renal injury. Thrombomodulin is a necessary factor in the anticoagulant protein C
      pathway and has inherent anti-inflammatory properties. We studied the effect of
      soluble thrombomodulin (sTM) in a hypoperfusion model of ischemic kidney injury.
      To markedly reduce infrarenal aortic blood flow and femoral arterial pressures,
      we clamped the suprarenal aorta of rats, occluding them 90%, for 60 min.
      Reversible acute kidney injury (AKI) occurred at 24 h in rats subjected to
      hypoperfusion. Histologic analysis at 24 h revealed acute tubular necrosis (ATN),
      and intravital two-photon microscopy showed flow abnormalities in the
      microvasculature and defects of endothelial permeability. Pretreatment with rat
      sTM markedly reduced both I-R-induced renal dysfunction and tubular histologic
      injury scores. sTM also significantly improved microvascular erythrocyte flow
      rates, reduced microvascular endothelial leukocyte rolling and attachment, and
      minimized endothelial permeability to infused fluorescence dextrans, assessed by
      intravital quantitative multiphoton microscopy. Furthermore, sTM administered 2 h
      after reperfusion protected against ischemia-induced renal dysfunction at 24 h
      and improved survival. By using an sTM variant, we also determined that the
      protective effects of sTM were independent of its ability to generate activated
      protein C. These data suggest that sTM may have therapeutic potential for
      ischemic AKI.

PMID- 19176700
TI  - Pharmacogenomic effect of vitamin E on kidney structure and function in
      transgenic mice with the haptoglobin 2-2 genotype and diabetes mellitus.
AB  - Polymorphic loci regulating oxidative stress are potential susceptibility genes
      for diabetic nephropathy (DN). Haptoglobin (Hp) is an antioxidant protein which
      serves to protect against oxidative stress induced by extracorpuscular
      hemoglobin. There are two alleles at the Hp locus, 1 and 2. The Hp 1 protein is a
      superior antioxidant to the Hp 2 protein. The Hp 2 allele has been associated
      with increased prevalence of DN and appears to be associated with a more rapid
      progression to end-stage renal disease. We sought to recapitulate this
      association between Hp genotype and DN in mice genetically modified at the Hp
      locus. We assessed morphometric, histologic, and functional parameters involved
      in the development and progression of DN in mice with diabetes mellitus (DM) with
      either the Hp 2-2 or Hp 1-1 genotype. Morphometric analysis demonstrated that
      glomerular and proximal tubular hypertrophy were significantly increased in Hp 2
      2 DM mice. Histological analysis demonstrated that Hp 2-2 DM mice had
      significantly more collagen type IV, smooth muscle actin, and increased renal
      iron deposition. Studies of renal function demonstrated creatinine clearance time
      and albuminuria were increased in Hp 2-2 DM mice. Vitamin E provided significant
      protection against the development of functional and histological features
      characteristic of DN to Hp 2-2 DM but not to Hp 1-1 DM mice. These studies serve
      to strengthen the association between the Hp 2-2 genotype and diabetic renal
      disease and suggest a pharmacogenomic interaction may exist between the Hp
      genotype and vitamin E.

PMID- 19176702
TI  - Low salt concentrations activate AMP-activated protein kinase in mouse macula
      densa cells.
AB  - The energy-sensing kinase AMP-activated protein kinase (AMPK) is associated with
      the sodium-potassium-chloride cotransporter NKCC2 in the kidney and
      phosphorylates it on a regulatory site in vitro. To identify a potential role for
      AMPK in salt sensing at the macula densa, we have used the murine macula densa
      cell line MMDD1. In this cell line, AMPK was rapidly activated by isosmolar low
      salt conditions. In contrast to the known salt-sensing pathway in the macula
      densa, AMPK activation occurred in the presence of either low sodium or low
      chloride and was unaffected by inhibition of NKCC2 with bumetanide. Assays using
      recombinant AMPK demonstrated activation of an upstream kinase by isosmolar low
      salt. The specific calcium/calmodulin-dependent kinase kinase inhibitor STO-609
      failed to suppress AMPK activation, suggesting that it was not part of the signal
      pathway. AMPK activation was associated with increased phosphorylation of the
      specific substrate acetyl-CoA carboxylase (ACC) at Ser(79), as well as increased
      NKCC2 phosphorylation at Ser(126). AMPK activation due to low salt concentrations
      was inhibited by an adenovirus construct encoding a kinase dead mutant of AMPK,
      leading to reduced ACC Ser(79) and NKCC2 Ser(126) phosphorylation. This work
      demonstrates that AMPK activation in macula densa-like cells occurs via isosmolar
      changes in sodium or chloride concentration, leading to phosphorylation of ACC
      and NKCC2. Phosphorylation of these substrates in vivo is predicted to increase
      intracellular chloride and so reduce the effect of salt restriction on
      tubuloglomerular feedback and renin secretion.

PMID- 19176701
TI  - The cardiotonic steroid hormone marinobufagenin induces renal fibrosis:
      implication of epithelial-to-mesenchymal transition.
AB  - We recently demonstrated that the cardiotonic steroid marinobufagenin (MBG)
      induced fibrosis in rat hearts through direct stimulation of collagen I secretion
      by cardiac fibroblasts. This stimulation was also responsible for the cardiac
      fibrosis seen in experimental renal failure. In this study, the effect of MBG on
      the development of renal fibrosis in rats was investigated. Four weeks of MBG
      infusion triggered mild periglomerular and peritubular fibrosis in the cortex and
      the appearance of fibrotic scars in the corticomedullary junction of the kidney.
      MBG also significantly increased the protein levels and nuclear localization of
      the transcription factor Snail in the tubular epithelia. It is known that
      activation of Snail is associated with epithelial-to-mesenchymal transition (EMT)
      during renal fibrosis. To examine whether MBG alone can trigger EMT, we used the
      porcine proximal tubular cell line LLC-PK1. MBG (100 nM) caused LLC-PK1 cells
      grown to confluence to acquire a fibroblast-like shape and have an invasive
      motility. The expressions of the mesenchymal proteins collagen I, fibronectin,
      and vimentin were increased twofold. However, the total level of E-cadherin
      remained unchanged. These alterations in LLC-PK1 cells in the presence of MBG
      were accompanied by elevated expression and nuclear translocation of Snail.
      During the time course of EMT, MBG did not have measurable inhibitory effects on
      the ion pumping activity of its natural ligand, Na(+)-K(+)-ATPase. Our data
      suggest that the MBG may be an important factor in inducing EMT and, through this
      mechanism, elevated levels of MBG in chronic renal failure may play a role in the
      progressive fibrosis.

PMID- 19176704
TI  - Postnatal developmental renal physiology: a study of historic significance.
AB  - This essay looks at the historic significance of an APS classic paper
      (http://www.the-aps.org/publications/classics/) that is freely available online:
      Falk G. Maturation of renal function in infant rats. Am J Physiol 181: 157-170,
      1955 (http://ajplegacy.physiology.org/cgi/reprint/181/1/157).

PMID- 19176703
TI  - Investigating the effect of genetic background on proteinuria and renal injury
      using two hypertensive strains.
AB  - An earlier linkage analysis conducted on a population derived from the Dahl salt
      sensitive hypertensive (S) and the spontaneously hypertensive rat (SHR)
      identified 10 genomic regions linked to several renal and/or cardiovascular
      traits. In particular, loci on rat chromosomes (RNO) 8 and 13 were linked to
      proteinuria, albuminuria, and renal damage. At both loci, the S allele was
      associated with increased proteinuria and renal damage. The current study aimed
      to confirm the linkage analysis and to evaluate the effect of genetic background
      on the ability of each locus (either RNO8 or RNO13) to exert a phenotypic
      difference when placed on a genetic background either susceptible (S rat) or
      resistant (SHR) to the development of renal disease. Congenic strains developed
      to transfer genomic segments from either RNO8 or RNO13 from the SHR onto the S
      genetic background [S.SHR(8) or S.SHR(13)] demonstrated significantly reduced
      proteinuria and improved renal function. Both congenic strains demonstrated
      significantly reduced glomerular and tubular injury, with renal interstitial
      fibrosis as the predominant pathological difference compared with the S. In
      contrast, transfer of RNO8 or RNO13 genomic regions from the S onto the resistant
      SHR genetic background [SHR.S(8) or SHR.S(13)] yielded no significant difference
      in proteinuria or glomerular, tubular, or interstitial injury compared with SHR.
      These findings demonstrate that genetic context plays a significant and important
      role in the phenotypic expression of genes influencing proteinuria on RNO8 and
      RNO13.

PMID- 19176705
TI  - How motivation influences breastfeeding duration among low-income women.
AB  - In-depth interviews were conducted with 44 low-income breastfeeding women to
      explore the incentives and disincentives to breastfeeding experienced within 6
      months postpartum. Using an individual net benefit maximization (INBM) framework
      based on economic theory, we assessed women's motivations, incentives, and
      disincentives for breastfeeding. Based on the framework and their experience
      breastfeeding, women fell into 3 groups: intrinsically motivated, extrinsically
      motivated, and successfully experienced with both intrinsic and extrinsic
      motivation. Successfully experienced women were most likely to breastfeed to 6
      months. Intrinsically motivated women valued breastfeeding but often required
      information and instruction to reach breastfeeding goals. Extrinsically motivated
      women were least likely to continue breastfeeding even with support and
      instruction. Providers can screen women to determine their experience and
      motivation then tailor interventions accordingly. Intrinsically motivated women
      may need support and instruction, extrinsically motivated women may benefit from
      motivational interviewing, and successfully experienced women may need only
      minimal breastfeeding counseling.

PMID- 19176706
TI  - Exhaled nitric oxide: time to employ or make redundant?

PMID- 19176707
TI  - Three-year follow-up after a two-year comprehensive pulmonary rehabilitation
      program.
AB  - The main objective of this study is to investigate the long-term effects, 3 years
      after the end of a 2-year pulmonary rehabilitation program with three weekly 1-h
      exercise sessions and 32 h of education in patients with chronic obstructive
      pulmonary disease. The method consists of open prospective observational study
      with 30 patients. Outcome measures were quality of life (QoL) (St George's
      Respiratory Questionnaire, SGRQ), physical exercise performance (6-min walking
      test, 6MWT), self-management abilities, lung function, hospitalization, and self
      reported exercise. FEV(1) at baseline was 40.1% of predicted. The participants
      had statistical and clinical significant decrease in SGRQ (improved QoL) and
      increase in 6MWT during the program. They maintained the level of health they
      achieved during the program in the next 3 years, with a stable SGRQ score (-0.5
      points, 95% CI -3.8 to 2.6 P=1.000) and 6MWT (+10 m 95% CI 28 to -4, P=0.273).
      Eighty percent of the participants had exercised at least 30 min three times a
      week from the end of the program to year 5. In conclusion, the participants had
      maintained their achieved level of health, improved their lung function slightly,
      and continued to exercise regularly 3 years after the end of the program.

PMID- 19176708
TI  - Palliative care services for those with chronic lung disease.
AB  - Excellent palliative care is available for patients with advanced lung cancer.
      Whether the same services are available for those with nonmalignant respiratory
      disease is less clear. A questionnaire was sent to 210 named respiratory
      physicians, each representing a major hospital in England, Wales, and Northern
      Ireland. A total of 107 replies were received; the response rate was 51.0%.
      Respondents cared for patients with chronic obstructive pulmonary disease,
      asbestosis, and diffuse parenchymal lung disease but only a third had
      responsibility for cystic fibrosis. Physicians were supported by a mean of 3.4
      respiratory nurse specialists per department and 73.8% had a specialist lung
      cancer nurse. In only 16 cases (20.3%) did that nurse extend care to those with
      nonmalignant disease. Only a minority reported easy access to hospice in-patient
      care or day care. About 21.5% of the respondents had formal policies in place for
      care of patients with chronic respiratory disease nearing the end of life, but
      87.9% of respondents had no formal process for initiating end of life discussions
      with those with terminal respiratory illness. Patients with advanced nonmalignant
      respiratory disease have less universal access to specialist palliative care
      services than do those with malignant lung disease, and in the majority of
      hospitals there is no formalized approach to end of life care issues with
      patients with chronic lung disease.

PMID- 19176710
TI  - Health-related quality of life measurement in cystic fibrosis: advances and
      limitations.
AB  - Health-related quality of life (HRQoL) measurement in cystic fibrosis (CF) allows
      the inclusion of the patient's perspective in research and clinical practice.
      HRQoL scales have been used for many purposes and this review focuses on how
      HRQoL measurement has been implemented in CF research and care. Specifically, the
      review considers 1) the instruments used to measure HRQoL, 2) the factors that
      influence how people report HRQoL, 3) the monitoring of HRQoL in clinical
      practice, 4) HRQoL as an outcome measure in interventions and clinical trials and
      5) whether HRQoL can predict survival. The challenge for the future is to use the
      available information to develop and evaluate psychological interventions that
      would be expected to improve HRQoL in children and adults with CF.

PMID- 19176709
TI  - Exhaled nitric oxide in the diagnosis and management of asthma: clinical
      implications.
AB  - Exhaled nitric oxide (eNO) used as an aid to the diagnosis and management of lung
      disease is receiving attention from pulmonary researchers and clinicians alike
      because it offers a noninvasive means to directly monitor airway inflammation.
      Research evidence suggests that eNO levels significantly increase in individuals
      with asthma before diagnosis, decrease with inhaled corticosteroid
      administration, and correlate with the number of eosinophils in induced sputum.
      These observations have been used to support an association between eNO levels
      and airway inflammation. This review presents an update on current opportunities
      regarding use of eNO in patient care, and more specifically on its potential
      usage for asthma diagnosis and monitoring. The review will also discuss factors
      that may complicate use of eNO as a diagnostic tool, including changes in disease
      severity, symptom response, and technical measurement issues. Regardless of the
      rapid, convenient, and noninvasive nature of this test, additional well-designed,
      long-term longitudinal studies are necessary to fully evaluate the clinical
      utility of eNO in asthma management.

PMID- 19176711
TI  - Breathing retraining for individuals with chronic obstructive pulmonary disease-
      a role for clinicians.

PMID- 19176712
TI  - Breathing retraining for individuals with chronic obstructive pulmonary disease-
      no role for clinicians.

PMID- 19176713
TI  - A fatal case of airway obstruction by an organic one-way valve.
AB  - We report a fatal case of airway obstruction. A tracheostomized, spontaneously
      breathing 39-year-old man developed dyspnea, cardiac, and respiratory arrest
      after tracheal cannula replacement. Inspection of the cannula showed a blood clot
      obstructing the tube. Autopsy showed pink foam in the trachea, pulmonary
      hyperinflation, and congested lung parenchyma. Histological examination showed
      acute pulmonary emphysema without any sign of blood inhalation. The probable
      pathophysiological mechanism is a clot creating a one-way valve allowing
      inspiration but not expiration, resulting in dyspnea and pulmonary
      hyperinflation.

PMID- 19176714
TI  - Saber-sheath trachea in a patient with bronchiolitis obliterans syndrome after
      lung transplantation.
AB  - Chronic rejection remains a major source of morbidity and mortality following
      lung transplantation. The clinical characteristics of chronic rejection involves
      bronchiolitis obliterans syndrome (BOS), which leads to progressive airway
      obstruction. Changes in intrathoracic tracheal dimensions and shape are commonly
      present in the setting of airway obstruction, leading to the narrowing of the
      intrathoracic trachea in the coronal plane with anteroposterior lengthening
      characteristic of the saber-sheath trachea deformity. We present a 64-year-old
      man who underwent left lung transplantation for idiopathic pulmonary fibrosis who
      later developed saber-sheath trachea as a result of chronic airway obstruction
      due to BOS.

PMID- 19176716
TI  - The barley magnesium chelatase 150-kd subunit is not an abscisic acid receptor.
AB  - Magnesium chelatase is the first unique enzyme of the chlorophyll biosynthetic
      pathway. It is composed of three gene products of which the largest is 150 kD.
      This protein was recently identified as an abscisic acid receptor in Arabidopsis
      (Arabidopsis thaliana). We have evaluated whether the barley (Hordeum vulgare)
      magnesium chelatase large subunit, XanF, could be a receptor for the
      phytohormone. The study involved analysis of recombinant magnesium chelatase
      protein as well as several induced chlorophyll-deficient magnesium chelatase
      mutants with defects identified at the gene and protein levels. Abscisic acid had
      no effect on magnesium chelatase activity and binding to the barley 150-kD
      protein could not be shown. Magnesium chelatase mutants showed a wild-type
      response in respect to postgermination growth and stomatal aperture. Our results
      question the function of the large magnesium chelatase subunit as an abscisic
      acid receptor.

PMID- 19176717
TI  - Molecular modeling and site-directed mutagenesis reveal essential residues for
      catalysis in a prokaryote-type aspartate aminotransferase.
AB  - We recently reported that aspartate (Asp) biosynthesis in plant chloroplasts is
      catalyzed by two different Asp aminotransferases (AAT): a previously
      characterized eukaryote type and a prokaryote type (PT-AAT) similar to bacterial
      and archaebacterial enzymes. The available molecular and kinetic data suggest
      that the eukaryote-type AAT is involved in the shuttling of reducing equivalents
      through the plastidic membrane, whereas the PT-AAT could be involved in the
      biosynthesis of the Asp-derived amino acids inside the organelle. In this work, a
      comparative modeling of the PT-AAT enzyme from Pinus pinaster (PpAAT) was
      performed using x-ray structures of a bacterial AAT (Thermus thermophilus;
      Protein Data Bank accession nos. 1BJW and 1BKG) as templates. We computed a three
      dimensional folding model of this plant homodimeric enzyme that has been used to
      investigate the functional importance of key amino acid residues in its active
      center. The overall structure of the model is similar to the one described for
      other AAT enzymes, from eukaryotic and prokaryotic sources, with two equivalent
      active sites each formed by residues of both subunits of the homodimer. Moreover,
      PpAAT monomers folded into one large and one small domain. However, PpAAT enzyme
      showed unique structural and functional characteristics that have been
      specifically described in the AATs from the prokaryotes Phormidium lapideum and
      T. thermophilus, such as those involved in the recognition of the substrate side
      chain or the "open-to-closed" transition following substrate binding. These
      predicted characteristics have been substantiated by site-direct mutagenesis
      analyses, and several critical residues (valine-206, serine-207, glutamine-346,
      glutamate-210, and phenylalanine-450) were identified and functionally
      characterized. The reported data represent a valuable resource to understand the
      function of this enzyme in plant amino acid metabolism.

PMID- 19176718
TI  - Ethylene modulates the role of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 in
      cross talk between salicylate and jasmonate signaling.
AB  - The plant hormones salicylic acid (SA), jasmonic acid (JA), and ethylene (ET)
      play crucial roles in the signaling network that regulates induced defense
      responses against biotic stresses. Antagonism between SA and JA operates as a
      mechanism to fine-tune defenses that are activated in response to multiple
      attackers. In Arabidopsis (Arabidopsis thaliana), NONEXPRESSOR OF PATHOGENESIS
      RELATED GENES1 (NPR1) was demonstrated to be required for SA-mediated suppression
      of JA-dependent defenses. Because ET is known to enhance SA/NPR1-dependent
      defense responses, we investigated the role of ET in the SA-JA signal
      interaction. Pharmacological experiments with gaseous ET and the ET precursor 1
      aminocyclopropane-1-carboxylic acid showed that ET potentiated SA/NPR1-dependent
      PATHOGENESIS-RELATED1 transcription, while it rendered the antagonistic effect of
      SA on methyl jasmonate-induced PDF1.2 and VSP2 expression NPR1 independent. This
      overriding effect of ET on NPR1 function in SA-JA cross talk was absent in the
      npr1-1/ein2-1 double mutant, demonstrating that it is mediated via ET signaling.
      Abiotic and biotic induction of the ET response similarly abolished the NPR1
      dependency of the SA-JA signal interaction. Furthermore, JA-dependent resistance
      against biotic attackers was antagonized by SA in an NPR1-dependent fashion only
      when the plant-attacker combination did not result in the production of high
      levels of endogenous ET. Hence, the interaction between ET and NPR1 plays an
      important modulating role in the fine tuning of the defense signaling network
      that is activated upon pathogen and insect attack. Our results suggest a model in
      which ET modulates the NPR1 dependency of SA-JA antagonism, possibly to
      compensate for enhanced allocation of NPR1 to function in SA-dependent activation
      of PR genes.

PMID- 19176719
TI  - Alternative splicing studies of the reactive oxygen species gene network in
      Populus reveal two isoforms of high-isoelectric-point superoxide dismutase.
AB  - Recent evidence has shown that alternative splicing (AS) is widely involved in
      the regulation of gene expression, substantially extending the diversity of
      numerous proteins. In this study, a subset of expressed sequence tags
      representing members of the reactive oxygen species gene network was selected
      from the PopulusDB database to investigate AS mechanisms in Populus. Examples of
      all known types of AS were detected, but intron retention was the most common.
      Interestingly, the closest Arabidopsis (Arabidopsis thaliana) homologs of half of
      the AS genes identified in Populus are not reportedly alternatively spliced. Two
      genes encoding the protein of most interest in our study (high-isoelectric-point
      superoxide dismutase [hipI-SOD]) have been found in black cottonwood (Populus
      trichocarpa), designated PthipI-SODC1 and PthipI-SODC2. Analysis of the expressed
      sequence tag libraries has indicated the presence of two transcripts of PthipI
      SODC1 (hipI-SODC1b and hipI-SODC1s). Alignment of these sequences with the PthipI
      SODC1 gene showed that hipI-SODC1b was 69 bp longer than hipI-SODC1s due to an AS
      event involving the use of an alternative donor splice site in the sixth intron.
      Transcript analysis showed that the splice variant hipI-SODC1b was differentially
      expressed, being clearly expressed in cambial and xylem, but not phloem, regions.
      In addition, immunolocalization and mass spectrometric data confirmed the
      presence of hipI-SOD proteins in vascular tissue. The functionalities of the
      spliced gene products were assessed by expressing recombinant hipI-SOD proteins
      and in vitro SOD activity assays.

PMID- 19176720
TI  - The low-oxygen-induced NAC domain transcription factor ANAC102 affects viability
      of Arabidopsis seeds following low-oxygen treatment.
AB  - Low-oxygen stress imposed by field waterlogging is a serious impediment to plant
      germination and growth. Plants respond to waterlogging with a complex set of
      physiological responses regulated at the transcriptional, cellular, and tissue
      levels. The Arabidopsis (Arabidopsis thaliana) NAC domain-containing gene ANAC102
      was shown to be induced under 0.1% oxygen within 30 min in both roots and shoots
      as well as in 0.1% oxygen-treated germinating seeds. Overexpression of ANAC102
      altered the expression of a number of genes, including many previously identified
      as being low-oxygen responsive. Decreasing ANAC102 expression had no effect on
      global gene transcription in plants but did alter expression patterns in low
      oxygen-stressed seeds. Increasing or decreasing the expression of ANAC102 did not
      affect adult plant survival of low-oxygen stress. Decreased ANAC102 expression
      significantly decreased germination efficiency following a 0.1% oxygen treatment,
      but increased expression had no effect on germination. This protective role
      during germination appeared to be specific to low-oxygen stress, implicating
      ANAC102 as an important regulator of seed germination under flooding.

PMID- 19176721
TI  - Trichoderma virens, a plant beneficial fungus, enhances biomass production and
      promotes lateral root growth through an auxin-dependent mechanism in Arabidopsis.
AB  - Trichoderma species belong to a class of free-living fungi beneficial to plants
      that are common in the rhizosphere. We investigated the role of auxin in
      regulating the growth and development of Arabidopsis (Arabidopsis thaliana)
      seedlings in response to inoculation with Trichoderma virens and Trichoderma
      atroviride by developing a plant-fungus interaction system. Wild-type Arabidopsis
      seedlings inoculated with either T. virens or T. atroviride showed characteristic
      auxin-related phenotypes, including increased biomass production and stimulated
      lateral root development. Mutations in genes involved in auxin transport or
      signaling, AUX1, BIG, EIR1, and AXR1, were found to reduce the growth-promoting
      and root developmental effects of T. virens inoculation. When grown under axenic
      conditions, T. virens produced the auxin-related compounds indole-3-acetic acid,
      indole-3-acetaldehyde, and indole-3-ethanol. A comparative analysis of all three
      indolic compounds provided detailed information about the structure-activity
      relationship based on their efficacy at modulating root system architecture,
      activation of auxin-regulated gene expression, and rescue of the root hair
      defective phenotype of the rhd6 auxin response Arabidopsis mutant. Our results
      highlight the important role of auxin signaling for plant growth promotion by T.
      virens.

PMID- 19176722
TI  - Temporal global expression data reveal known and novel salicylate-impacted
      processes and regulators mediating powdery mildew growth and reproduction on
      Arabidopsis.
AB  - Salicylic acid (SA) is a critical mediator of plant innate immunity. It plays an
      important role in limiting the growth and reproduction of the virulent powdery
      mildew (PM) Golovinomyces orontii on Arabidopsis (Arabidopsis thaliana). To
      investigate this later phase of the PM interaction and the role played by SA, we
      performed replicated global expression profiling for wild-type and SA
      biosynthetic mutant isochorismate synthase1 (ics1) Arabidopsis from 0 to 7 d
      after infection. We found that ICS1-impacted genes constitute 3.8% of profiled
      genes, with known molecular markers of Arabidopsis defense ranked very highly by
      the multivariate empirical Bayes statistic (T(2) statistic). Functional analyses
      of T(2)-selected genes identified statistically significant PM-impacted
      processes, including photosynthesis, cell wall modification, and alkaloid
      metabolism, that are ICS1 independent. ICS1-impacted processes include redox,
      vacuolar transport/secretion, and signaling. Our data also support a role for
      ICS1 (SA) in iron and calcium homeostasis and identify components of SA cross
      talk with other phytohormones. Through our analysis, 39 novel PM-impacted
      transcriptional regulators were identified. Insertion mutants in one of these
      regulators, PUX2 (for plant ubiquitin regulatory X domain-containing protein 2),
      results in significantly reduced reproduction of the PM in a cell death
      independent manner. Although little is known about PUX2, PUX1 acts as a negative
      regulator of Arabidopsis CDC48, an essential AAA-ATPase chaperone that mediates
      diverse cellular activities, including homotypic fusion of endoplasmic reticulum
      and Golgi membranes, endoplasmic reticulum-associated protein degradation, cell
      cycle progression, and apoptosis. Future work will elucidate the functional role
      of the novel regulator PUX2 in PM resistance.

PMID- 19176723
TI  - The temperature-sensitive brush mutant of the legume Lotus japonicus reveals a
      link between root development and nodule infection by rhizobia.
AB  - The brush mutant of Lotus japonicus exhibits a temperature-dependent impairment
      in nodule, root, and shoot development. At 26 degrees C, brush formed fewer
      nodules, most of which were not colonized by rhizobia bacteria. Primary root
      growth was retarded and the anatomy of the brush root apical meristem revealed
      distorted cellular organization and reduced cell expansion. Reciprocal grafting
      of brush with wild-type plants indicated that this genotype only affected the
      root and that the shoot phenotype was a secondary effect. The root and nodulation
      phenotype cosegregated as a single Mendelian trait and the BRUSH gene could be
      mapped to the short arm of chromosome 2. At 18 degrees C, the brush root anatomy
      was rescued and similar to the wild type, and primary root length, number of
      infection threads, and nodule formation were partially rescued. Superficially,
      the brush root phenotype resembled the ethylene-related thick short root
      syndrome. However, treatment with ethylene inhibitor did not recover the observed
      phenotypes, although brush primary roots were slightly longer. The defects of
      brush in root architecture and infection thread development, together with intact
      nodule architecture and complete absence of symptoms from shoots, suggest that
      BRUSH affects cellular differentiation in a tissue-dependent way.

PMID- 19176724
TI  - Variety influences habituation of motivated behavior for food and energy intake
      in children.
AB  - BACKGROUND: Research has shown that variety reduces the rate of habituation, or a
      general reduction in the rate of responding, for low-energy-density (LED) and
      high-energy-density (HED) foods. OBJECTIVE: We assessed whether the effects of
      variety on habituation of motivation to eat are different in overweight and lean
      children. DESIGN: Overweight and lean children (n = 84) were randomly assigned to
      groups that varied as to whether they received their favorite or a variety of LED
      or HED foods. RESULTS: Habituation was slower for overweight than for
      nonoverweight children (P = 0.008), for a variety of foods than for the same
      foods (P < 0.001), and for LED than for HED foods (P < 0.001). Energy intake was
      greater for overweight than for nonoverweight children provided with variety (P =
      0.004) and was greater for overweight or nonoverweight children provided with the
      same food (P < 0.001). A variety of HED foods increased energy intake more than
      did the same HED foods (P < 0.001); this increase was greater than energy intake
      with the same or a variety of LED foods (P < 0.001). Children who sensitized, or
      showed an increase in responding before habituating, showed slower habituation (P
      < 0.001) and consumed more energy (P = 0.039) than did children who did not
      sensitize. CONCLUSIONS: Habituation is influenced by variety of foods, and
      overweight children increase energy intake more with variety than do leaner
      children. Research is needed to evaluate mechanisms of how variety influences the
      motivation to eat and energy intake, and how the variety effect can be used to
      influence intake across multiple eating occasions in children.

PMID- 19176725
TI  - Can there be a single best measure of reported physical activity?

PMID- 19176726
TI  - Comparison of 2 diets with either 25% or 10% of energy as casein on energy
      expenditure, substrate balance, and appetite profile.
AB  - BACKGROUND: An increase in the protein content of a diet results in an increase
      in satiety and energy expenditure. It is not clear to what extent a specific type
      of protein has such effects. OBJECTIVE: The objective was to compare the effects
      of 2 diets with either 25% or 10% of energy from casein (25En% and 10En% casein
      diets), as the only protein source, on energy expenditure, substrate balance, and
      appetite profile. DESIGN: During a 36-h stay in a respiration chamber, 24 healthy
      subjects [12 men and 12 women, body mass index (in kg/m(2)) of 22.4 +/- 2.4, age
      25 +/- 7 y] received isoenergetic diets according to subject-specific energy
      requirements: 25En% diet (25%, 20%, and 55% of energy as protein, fat, and
      carbohydrate, respectively) and 10En% diet (10%, 35%, and 55% of energy as
      protein, fat, and carbohydrate, respectively) in a randomized crossover design.
      Three days before the diets began, the subjects consumed a similar diet at home.
      Energy expenditure, substrate oxidation, and appetite scores were measured.
      RESULTS: The 25En% casein diet resulted in a 2.6% higher 24-h total energy
      expenditure (9.30 +/- 0.24 compared with 9.07 +/- 0.24 MJ/d; P < 0.01) and a
      higher sleeping metabolic rate (6.74 +/- 0.16 compared with 6.48 +/- 0.17 MJ/d; P
      < 0.001) than did the 10En% casein diet. With the 25En% casein diet, compared
      with the 10En% casein diet, the subjects were in positive protein balance (0.57
      +/- 0.05 compared with -0.08 +/- 0.03 MJ/d; P < 0.0001) and negative fat balance
      (-0.83 +/- 0.14 compared with 0.11 +/- 0.17 MJ/d; P < 0.0001), whereas positive
      carbohydrate balances were not significantly different between diets. Satiety was
      33% higher with the 25En% casein diet than with the 10En% casein diet (P < 0.05).
      CONCLUSION: A 25En% casein diet boosts energy expenditure, protein balance,
      satiety, and negative fat balance, which is beneficial to body weight management.

PMID- 19176727
TI  - Red blood cell delta15N: a novel biomarker of dietary eicosapentaenoic acid and
      docosahexaenoic acid intake.
AB  - BACKGROUND: The long-chain omega-3 (n-3) fatty acids derived from fish,
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a
      reduced risk of cardiovascular disease and other chronic diseases. Study of the
      associations between EPA and DHA intake and disease requires a valid biomarker of
      dietary intake; however, the direct measurement of tissue fatty acid
      concentrations is expensive and time consuming. OBJECTIVE: Because the nitrogen
      stable isotope ratio ((15)N/(14)N, expressed as delta(15)N) is elevated in fish,
      we investigated whether delta(15)N is a valid alternative biomarker of EPA and
      DHA intake. DESIGN: We examined the relation between red blood cell (RBC)
      delta(15)N and RBC EPA and DHA in a community-based sample of 496 Yup'ik Eskimos
      with widely varying intake of n-3 fatty acids. We also assessed the correlation
      between delta(15)N and dietary EPA and DHA intake based on 24-h dietary recalls
      and 3-d food records completed by a subset of 221 participants. RESULTS: RBC
      delta(15)N was strongly correlated with RBC EPA and DHA (r = 0.83 and 0.75,
      respectively). These correlations differed only modestly by sex and age class.
      RBC delta(15)N also correlated with dietary EPA and DHA intake (r = 0.47 and
      0.46, respectively) and did not differ by sex and age. CONCLUSIONS: The results
      strongly support the validity of RBC delta(15)N as a biomarker of EPA and DHA
      intake. Because the analysis of RBC delta(15)N is rapid and inexpensive, this
      method could facilitate wide-scale assessment of EPA and DHA intake in clinical
      and epidemiologic studies.

PMID- 19176728
TI  - Role of docosahexaenoic acid in maternal and child mental health.
AB  - Mental health problems in women and children represent a significant public
      health problem worldwide, especially in developing countries. The role of
      nutrition as a cost-effective approach in the prevention and management of these
      conditions has received recent attention, particularly nutrients such as iron,
      zinc, and n-3 (omega-3) fatty acids, which play a role in brain structure and
      function. The objective of this article was to review current evidence on the
      relation between n-3 fatty acids, especially docosahexaenoic acid (DHA), and
      maternal and child mental health disorders. Human studies published in English
      were identified from Medline databases (1966 to June 2008) by using key search
      terms and review articles. A summary of the role of DHA in the human brain is
      followed by a review of human studies, both observational and intervention
      trials, that examine the relation between n-3 fatty acids such as DHA and
      depression and child mental health disorders. Observational studies support a
      direct association between poor n-3 fatty acid status and increased risk of
      maternal depression and childhood behavioral disorders such as attention-deficit
      hyperactivity disorder (ADHD). However, evidence from intervention trials is
      weak. Most of the studies reviewed had small sample sizes and were conducted in
      clinically diagnosed samples, with no placebo-controlled groups. Little is known
      about the benefits of DHA in the prevention of maternal depression and ADHD.
      Large, well-designed, community-based prevention trials are needed.

PMID- 19176730
TI  - Systematic review and meta-analysis of the baseline concentrations and
      physiologic responses of gut hormones to food in eating disorders.
AB  - BACKGROUND: Disturbances in gastrointestinal hormones have been widely identified
      in persons with eating disorders (EDs) and have been implicated in their clinical
      pathologies. OBJECTIVE: The objective was to identify, critically examine, and
      summarize studies investigating the short-term response of gastrointestinal
      hormones to food in persons with an ED, including the subtypes anorexia nervosa
      and bulimia nervosa. DESIGN: A priori inclusion and exclusion criteria were set
      and included a procedure in which a test meal or glucose load was given and blood
      hormone concentrations measured. All studies included a healthy control group for
      comparison. The outcome variable was defined as the mean difference between
      fasting plasma hormone concentrations and the maximum postprandial peak or nadir.
      The difference in baseline values between groups was also examined. Pooled
      standardized mean differences were calculated and analyzed where possible.
      RESULTS: A total of 28 studies were identified, including sufficient studies to
      perform a meta-analysis for ghrelin, peptide YY, cholecystokinin, insulin, and
      pancreatic polypeptide. Persons with an ED had higher baseline concentrations of
      ghrelin (large effect), peptide YY (medium effect), and cholecystokinin (medium
      effect for ED, large effect for anorexia nervosa). The response of insulin to
      food was decreased in persons with an ED (medium effect). No further differences
      were found in the release of gut peptides to a standardized test meal.
      CONCLUSIONS: All of the studies had low power for the different subtypes of EDs.
      High heterogeneity among the studies was observed, and limitations are discussed.
      The findings suggest that the physiologic changes observed in patients with EDs
      are highly variable and subject to multiple confounding factors.

PMID- 19176729
TI  - Maternal depressive symptoms and infant growth in rural Bangladesh.
AB  - BACKGROUND: Depressive disorders are a major source of disability among low
      income mothers in developing countries. OBJECTIVES: The objectives were to
      examine the association of maternal depressive symptoms and infant growth among
      infants in rural Bangladesh and to examine how the relation is affected by infant
      irritability and caregiving practices. DESIGN: Infant growth was measured among
      221 infants at 6 and 12 mo. Mothers reported their depressive symptoms and
      perceptions of their infant's temperament, and a home observation of caregiving
      was conducted. RESULTS: At 6 mo, 18% of infants were stunted (length-for-age < -2
      z scores). At 12 mo, 36.9% of infants were stunted; infants of mothers with
      depressive symptoms had a 2.17 higher odds of being stunted (95% CI: 1.24, 3.81;
      P = 0.007) than did infants of mothers with few symptoms (45.3% compared with
      27.6%). In a multivariate regression analysis, maternal depressive symptoms were
      associated with 12-mo length-for-age, adjusted for 6-mo length-for-age, maternal
      education, infant sex, birth order, receipt of iron and zinc, months breastfed,
      maternal perception of infant temperament, and caregiving observations. Maternal
      depressive symptoms were not related to 12-mo weight-for-length. The relation
      between depressive symptoms and infant growth was not moderated by maternal
      perceptions of infant temperament, but was partially mediated by caregiving.
      CONCLUSIONS: The finding that infants of mothers with depressive symptoms in
      Bangladesh experience poor linear growth may extend to other low-income countries
      with high rates of food insecurity. Interventions to promote growth in infants
      should include prevention or treatment of maternal depressive disorders and
      strategies to ensure adequate food security.

PMID- 19176731
TI  - Maternal and child mental health: role of nutrition. Introduction.

PMID- 19176732
TI  - Opportunities and challenges in conducting systematic reviews to support the
      development of nutrient reference values: vitamin A as an example.
AB  - Nutrient reference values have significant public health and policy implications.
      Given the importance of defining reliable nutrient reference values, there is a
      need for an explicit, objective, and transparent process to set these values. The
      Tufts Medical Center Evidence-based Practice Center assembled a group of
      nutrition experts from academic institutions and federal government agencies, led
      participants in discussions, conducted exercises in formulating questions and
      evidence review criteria that would be amenable to systematic reviews of the
      scientific literature, performed a literature search on the questions to identify
      potentially relevant publications, and identified challenges and limitations of
      applying this method to support the development of nutrient reference values
      using vitamin A as an example. The workgroup concluded that the systematic review
      approach could be productively used to inform the development of reference
      values. Challenges identified in this exercise include prioritizing and defining
      research questions when the volume of literature is large, relying on
      intermediate (surrogate) outcomes when few or no studies directly linking
      nutrient intake with clinical outcomes are available, and determining reliable
      nutrient biomarkers. Ultimately, an objective, unbiased systematic review of a
      defined question could be useful, not only in helping to set nutrient reference
      values, but also for increasing the transparency of the decision making process.

PMID- 19176733
TI  - Green tea catechin plus caffeine supplementation to a high-protein diet has no
      additional effect on body weight maintenance after weight loss.
AB  - BACKGROUND: Green tea (epigallocatechin gallate + caffeine) and protein each were
      shown to improve body weight maintenance after weight loss. OBJECTIVE: We
      investigated the effect of a green tea-caffeine mixture added to a high-protein
      (HP) diet on weight maintenance (WM) after body weight loss in moderately obese
      subjects. DESIGN: A randomized, placebo-controlled, double-blind parallel trial
      was conducted in 80 overweight and moderately obese subjects [age (mean +/- SD):
      44 +/- 2 y; body mass index (BMI; in kg/m(2)): 29.6 +/- 2.0] matched for sex,
      age, BMI, height, body mass, and with a habitually low caffeine intake. A very
      low-energy diet intervention during 4 wk was followed by 3 mo of WM; during the
      WM period, the subjects received a green tea-caffeine mixture (270 mg
      epigallocatechin gallate + 150 mg caffeine/d) or placebo, both in addition to an
      adequate protein (AP) diet (50-60 g protein/d) or an HP diet (100-120 g
      protein/d). RESULTS: Subjects lost 7.0 +/- 1.6 kg, or 8.2 +/- 2.0%, body weight
      (P < 0.001). During the WM phase, WM, resting energy expenditure, and fat-free
      mass (FFM) increased relatively in both the HP groups and in the AP + green tea
      caffeine mixture group (P < 0.05), whereas respiratory quotient and body fat mass
      decreased, all compared with the AP + placebo group. Satiety increased only in
      both HP groups (P < 0.05). The green tea-caffeine mixture was only effective with
      the AP diet. CONCLUSION: The green tea-caffeine mixture, as well as the HP diet,
      improved WM independently through thermogenesis, fat oxidation, sparing FFM, and,
      for the HP diet, satiety; a possible synergistic effect failed to appear.

PMID- 19176734
TI  - Maternal mental health: program and policy implications.
AB  - Despite increasing evidence of the seriousness of maternal depression, the number
      of individuals affected, and the impact of maternal depression on infant growth
      and development, maternal mental health has not become a component of the primary
      health care system in many parts of the world. The impact appears to be greatest
      in South Asia, possibly among low-income families. Some interventions, such as
      increases in social support or the education of mothers about responsive
      caregiving, appear to be effective in reducing maternal distress. However, we do
      not yet have recognized, effective, and scalable strategies to treat maternal
      depression or reduce the more common maternal distress. Efforts are needed to
      increase the availability of programs for maternal mental health and to develop
      simple interventions to reduce maternal distress that can be used by primary
      health care providers. Second, efforts are needed to develop policies that
      include maternal mental health. These efforts should build on research and on
      international conventions and statements, such as the recent United Nations Fund
      for Population Activities/World Health Organization recommendation for a
      comprehensive approach to preventing and treating maternal depression.

PMID- 19176736
TI  - Models linking nutritional deficiencies to maternal and child mental health.
AB  - The primary goal of this article was to illustrate how nutritional deficiencies
      can translate into adult or child mental health problems. Whereas brain
      development and function play an essential role in the etiology and maintenance
      of mental health problems, what is required are models that go beyond nutrition
      brain relations and integrate the contributions of nutritionally related
      contextual and behavioral characteristics. Four such models are presented. The
      multiple risks model derives from evidence showing covariance between nutritional
      deficiencies and other life stressors. Given that poorly nourished adults may be
      less able to actively cope with stressors, nutritional deficiencies may
      accentuate the negative impact of stress exposure on mental health. The cross
      generational model is based on evidence showing less adequate patterns of mother
      child interactions when mothers are poorly nourished. Impairments in mother-child
      interactions increase the likelihood of child mental health problems and the risk
      of subsequent child nutritional deficiencies. The attachment model derives from
      evidence showing that poorly nourished infants may be less likely to elicit the
      types of maternal child-rearing patterns that translate into secure infant-mother
      attachments. Insecure attachments in infancy are associated with an increased
      risk of both short-term and long-term child mental health problems. The
      temperament model is based on evidence documenting that certain patterns of
      infant temperament are related to an increased risk of later behavioral problems.
      Infant nutritional deficiencies can influence the development of temperament, and
      certain temperament patterns can contribute to an increased risk of infant
      nutritional deficiencies.

PMID- 19176735
TI  - Role of zinc in maternal and child mental health.
AB  - Mental health problems in women, children, and adolescents are a significant
      public health issue. Given current barriers to the effective treatment of these
      problems, researchers are looking to the field of nutrition for potential
      alternatives to better understand and address mental health issues. The purpose
      of this article was to review current evidence on the relation between zinc and
      mental health disorders with a focus on 2 mental health problems that commonly
      affect women and children: depression and attention-deficit hyperactivity
      disorder (ADHD). A literature search of the databases Medline and PsychInfo was
      conducted with the use of key terms. The review included articles from 1975 to
      May 2008, but focused on articles published in recent years. Relations between
      zinc concentrations and behavior in animals; the relation between zinc
      deficiency, depression, and ADHD in patient and community samples; and the
      potential biological mechanisms for these relations were explored. The data
      support a relation between low concentrations of zinc and mental health problems,
      especially in at-risk populations. Evidence for the potential use of zinc in
      treating mental health problems comes mainly from patient populations and is
      strongest when zinc is given in combination with pharmacologic treatment. Less
      conclusive evidence exists for the effectiveness of zinc alone or in general
      community samples. Recommendations for further research in this area are
      provided.

PMID- 19176737
TI  - Treatment response to standard of care for severe anemia in pregnant women and
      effect of multivitamins and enhanced anthelminthics.
AB  - BACKGROUND: Severe anemia (hemoglobin < 70 g/L) in pregnancy may increase the
      risk of maternal and perinatal mortality. OBJECTIVES: We assessed response to
      standard treatment with high-dose iron-folic acid for 90 d and single-dose (500
      mg) mebendazole among severely anemic pregnant women in periurban Karachi,
      Pakistan. In addition, we evaluated the efficacy of 2 enhanced treatment
      regimens. DESIGN: We screened pregnant women (n = 6288) for severe anemia and
      provided them all with the standard treatment. To test the efficacy of 2
      additional treatments, women were randomly assigned to standard treatment alone
      (control) or with 100 mg mebendazole twice daily for 3 d or 90 d of daily
      multivitamins or both using a 2 x 2 factorial design. RESULTS: Prevalence of
      severe anemia was high (10.5%) during pregnancy. Prevalence of geohelminths and
      malaria was low. Treatment response was defined as hemoglobin > 100 g/L at the 90
      d or > or = 25 g/L at the 60-d follow-up visit. The standard-of-care treatment
      resulted in a response rate of 49% at follow-up, although an adherence of > or =
      85% elicited a higher response (67%). The effect of the additional treatments was
      weak. Although response was higher in the enhanced groups than for the standard
      treatment at the final assessment, the differences were not statistically
      significant. However, hemoglobin concentration increased significantly in all
      groups and was higher in the enhanced mebendazole group compared with the
      standard group (P < 0.05). CONCLUSIONS: Iron deficiency was high in this
      population, and the standard-of-care treatment resulted in a treatment response
      of 50%, although better treatment adherence showed a higher response.
      Multivitamins and the enhanced mebendazole regimen had a modest benefit over and
      above the standard treatment.

PMID- 19176738
TI  - Leptin: weight management and beyond. Introduction to the symposium.

PMID- 19176739
TI  - Dietary calcium does not exacerbate phytate inhibition of zinc absorption by
      women from conventional diets.
AB  - BACKGROUND: Although calcium inhibits zinc bioavailability in rats, especially
      from high-phytate diets, the effect of calcium on zinc absorption by humans from
      practical diets remains unclear. OBJECTIVE: The objective was to test the
      inhibitory effect of dietary calcium, in Western diets with high and low phytate
      content, on zinc absorption. DESIGN: Using a 2 x 2 factorial design, zinc
      absorption was determined in 10 healthy women from 1-d diets with moderate and
      high calcium contents of approximately 700 and 1800 mg/d and low and high phytate
      contents of approximately 440 and 1800 mg/d. Absorption was measured by using
      extrinsically added (65)Zn and subsequent whole-body scintillation counting.
      RESULTS: Mean (+/-SE) fractional zinc absorption was 32.8 +/- 2.3% from the
      moderate-calcium, low-phytate diet; 26.9 +/- 2.4% from the moderate-calcium, high
      phytate diet; 39.4 +/- 2.4% from the high-calcium, low-phytate diet; and 26.2 +/-
      2.3% from the high-calcium, high-phytate diet. The respective values for absolute
      zinc absorption were 3.8 +/- 0.3, 3.0 +/- 0.3, 4.5 +/- 0.3, and 3.2 +/- 0.3 mg/d.
      Phytate significantly reduced fractional zinc absorption by approximately 10
      percentage points and reduced absolute zinc absorption by 25%, or approximately 1
      mg/d. Differences in dietary calcium did not affect zinc absorption, regardless
      of a high or low dietary phytate content. CONCLUSIONS: In healthy women consuming
      1-d menus of ordinary foods (some fortified with calcium), dietary phytate
      reduces zinc absorption, but calcium does not impair zinc absorption, regardless
      of whether dietary phytate is low or high.

PMID- 19176740
TI  - Leptin in humans: lessons from translational research.
AB  - Leptin has emerged over the past decade as a key hormone in not only the
      regulation of food intake and energy expenditure but also in the regulation of
      neuroendocrine and immune function as well as the modulation of glucose and fat
      metabolism as shown by numerous observational and interventional studies in
      humans with (complete) congenital or relative leptin deficiency. These results
      have led to proof-of-concept studies that have investigated the effect of leptin
      administration in subjects with complete (congenital) leptin deficiency caused by
      mutations in the leptin gene as well as in humans with relative leptin
      deficiency, including states of lipoatrophy or negative energy balance and
      neuroendocrine dysfunction, as for instance seen with hypothalamic amenorrhea in
      states of exercise-induced weight loss. In those conditions, most neuroendocrine,
      metabolic, or immune disturbances can be restored by leptin administration.
      Leptin replacement therapy is thus a promising approach in several disease
      states, including congenital complete leptin deficiency, states of energy
      deprivation, including anorexia nervosa or milder forms of hypothalamic
      amenorrhea, as well as syndromes of insulin resistance seen in conditions such as
      congenital or acquired lipodystrophy. In contrast, states of energy excess such
      as garden-variety obesity are associated with hyperleptinemia that reflects
      either leptin tolerance or leptin resistance. For those conditions, development
      of leptin sensitizers is currently a focus of pharmaceutical research. This
      article summarizes our current understanding of leptin's role in human physiology
      and its potential role as a novel therapeutic option in human disease states
      associated with a new hormone deficiency, ie, leptin deficiency.

PMID- 19176741
TI  - Dietary reference intakes for vitamin D: justification for a review of the 1997
      values.
AB  - Recent Institute of Medicine (IOM) reviews of the process for deriving Dietary
      Reference Intakes (DRIs) suggest that determining the need for a new nutrient
      review should be evaluated against criteria set a priori. After selecting the
      criterion of significant new and relevant research, a working group of US and
      Canadian government scientists used results from a systematic review and 2
      conferences on vitamin D and health to evaluate whether significant new and
      relevant scientific evidence had become available since the 1997 IOM publication
      of the DRIs for vitamin D. This working group concluded that there appears to be
      new research meeting the criteria for 4 key DRI questions. The new research is of
      larger quantity and quality for the elderly than for other groups, but overall 1)
      adds to the bone-related and status evidence available to the 1997 DRI Committee
      for several of the life-stage groups, 2) identifies new outcomes with respect to
      risk of falls and performance measures in the elderly and potential adverse
      effects, and 3) provides additional information on dose-response relations
      between intakes and circulating 25-hydroxyvitamin D concentrations and between 25
      hydroxyvitamin D concentrations and several health outcomes (ie, bone-related
      outcomes for all ages and risk of falls and performance measures in older
      adults). Members of the working group concluded that significant new and relevant
      research was available for reviewing the existing DRIs for vitamin D while
      leaving the decision of whether the new research will result in changes to the
      current DRIs to a future IOM-convened DRI committee.

PMID- 19176742
TI  - Generation of epidermal growth factor-expressing Lactococcus lactis and its
      enhancement on intestinal development and growth of early-weaned mice.
AB  - BACKGROUND: Epidermal growth factor (EGF) plays an important role in intestinal
      proliferation and differentiation. Previous studies by others have shown that
      administration of EGF into the ileum lumen enhances intestinal development.
      OBJECTIVE: The objective was to examine the feasibility of expressing and
      delivering EGF via Lactococcus lactis to early-weaned mice to enhance intestinal
      development at this critical transition stage. DESIGN: EGF-expressing L. lactis
      (EGF-LL) was generated with a recombinant approach. Early-weaned mice were orally
      gavaged with the recombinant bacteria. Body weight, mean villous height, and
      crypt depth in the intestine were measured to examine the influence of EGF-LL on
      the intestinal development of early-weaned mice in vivo. RESULTS: Populations of
      EGF-LL were shown to survive throughout the intestinal tract, and the recombinant
      EGF protein was also detected in intestinal contents. Weight gain was
      significantly greater in mice that received EGF-LL than in control mice fed
      phosphate-buffered saline or L. lactis transformed with the empty vector backbone
      but was comparable with that of the positive control mice that received
      recombinant human EGF. EGF-LL increased mean villous height and crypt depth in
      the intestine. Immunohistochemistry also confirmed that enterocyte proliferation
      was enhanced in mice that received EGF-LL, as evidenced by the greater number of
      cells stained with proliferative cell nuclear antigen in the intestine.
      CONCLUSIONS: This study showed that EGF-LL had beneficial effects on the
      intestinal growth of newly weaned mice. The combination of growth factor delivery
      and a probiotic approach may offer possibilities for formulating dietary
      supplements for children during their weaning transition stage.

PMID- 19176743
TI  - Dietary intervention for blood pressure control: a call for action!

PMID- 19176744
TI  - From observation to experimentation: leptin action in the mediobasal
      hypothalamus.
AB  - The burgeoning obesity epidemic has fueled the drive to describe,
      mechanistically, metabolic homeostasis. From the early theories implicating
      glucose as a principal modulator grew an understanding of a complex array of
      metabolic signals, sensed by peripheral organs along with specific locations
      within the central nervous system (CNS). The discovery that leptin, an adipose
      derived hormone, acts within the mediobasal hypothalamus to control food intake
      and energy expenditure ushered in a decade of research that went on to describe
      not only the specific nuclei and cell type, such as proopiomelanocortin neurons
      of the arcuate nucleus, that respond to leptin but also the signaling cascades
      that mediated its effects. This review thus highlights the sites and mechanisms
      of action of leptin, both in the hypothalamus and in extrahypothalamic sites
      within the CNS, and shows our current knowledge and direction of future research
      aimed at understanding the multifunctional role of leptin in maintaining
      metabolic homeostasis.

PMID- 19176745
TI  - Viscosity of oat bran-enriched beverages influences gastrointestinal hormonal
      responses in healthy humans.
AB  - Viscous fibers, including beta-glucan in oat bran, favorably affect satiety as
      well as postprandial carbohydrate and lipid metabolism. However, effects of fiber
      viscosity on modulation of satiety-related gut hormone responses are largely
      unknown. We examined the effects of modified oat bran, with or without its
      natural viscosity, on sensations of appetite and satiety-related gastrointestinal
      (GI) hormone responses to establish the relevance of viscosity of beta-glucan in
      oat bran. Twenty healthy, normal-weight participants (16 female, 4 male, aged
      22.6 +/- 0.7 y) ingested 2 isocaloric (1250 kJ) 300-mL oat bran beverages with
      low or high viscosity (carbohydrates, 57.9 g; protein, 7.8 g; fat, 3.3 g; fiber,
      10.2 g) after a 12-h fast in randomized order. Viscosity of the low-viscosity oat
      bran beverage was reduced by beta-glucanase treatment. Blood samples were drawn
      before and 15, 30, 45, 60, 90, 120, and 180 min after beverage consumption. The
      oat bran beverage with low viscosity induced a greater postprandial increase in
      satiety (P = 0.048) and plasma glucose (P < 0.001), insulin (P = 0.008),
      cholecystokinin (P = 0.035), glucagon-like peptide 1 (P = 0.037), and peptide YY
      (P = 0.051) and a greater decrease in postprandial ghrelin (P = 0.009) than the
      beverage with high-viscosity oat bran. Gastric emptying as measured by
      paracetamol absorption was also faster (P = 0.034) after low-viscosity oat bran
      beverage consumption. In conclusion, viscosity differences in oat beta-glucan in
      a liquid meal with identical chemical composition strongly influenced not only
      glucose and insulin responses, but also short-term gut hormone responses,
      implying the importance of food structure in the modulation of postprandial
      satiety-related physiology.

PMID- 19176746
TI  - Homeostatic and hedonic signals interact in the regulation of food intake.
AB  - Food intake is regulated by 2 complementary drives: the homeostatic and hedonic
      pathways. The homeostatic pathway controls energy balance by increasing the
      motivation to eat following depletion of energy stores. In contrast, hedonic or
      reward-based regulation can override the homeostatic pathway during periods of
      relative energy abundance by increasing the desire to consume foods that are
      highly palatable. In contrast to the consumption of food, the motivation to use
      drugs of abuse is mediated only by the reward pathway. In this article we review
      the extensive research that has identified several mechanisms by which repeated
      exposure to drugs of abuse alters neuronal function and increases the
      motivational incentive to obtain and use these substances. We then compare our
      current understanding of drug-induced changes in neuronal reward circuitry with
      what is known about the consequences of repeated consumption of highly palatable
      foods such as high-fat and high-sugar diets. Next, we discuss the normal
      homeostatic regulation of food intake, which is a unique aspect of food
      addiction. Finally, we discuss the clinical implications of these neuronal
      adaptations in the context of obesity and neuropsychiatric syndromes such as
      bulimia nervosa and Prader-Willi syndrome.

PMID- 19176747
TI  - Food addiction in humans.
AB  - Most of the evidence for or against food addiction in humans focuses on
      similarities between food craving and drug craving. There are numerous parallels
      in neuroanatomy, neurochemistry, and learning. Indeed, brain mechanisms for
      craving probably evolved to promote seeking of natural rewards and are taken over
      by drugs of abuse. Healthy, normal weight individuals, by definition, do not
      suffer from food addiction; however, overweight and obese individuals could meet
      clinical criteria. Palatable foods are not responsible for the obesity problem,
      because even nonpalatable foods can come to be desired and potentially
      overconsumed. It may be the way in which foods are consumed (e.g. alternating
      access and restriction) rather than their sensory properties that leads to an
      addictive eating pattern.

PMID- 19176749
TI  - Intestinal neoplasia induced by low dietary folate is associated with altered
      tumor expression profiles and decreased apoptosis in mouse normal intestine.
AB  - Epidemiological studies suggest that low dietary folate increases risk for
      intestinal neoplasia. We recently developed a unique tumor model in which mice
      fed low dietary folate developed DNA damage and intestinal tumors. To identify
      additional mechanisms by which reduced folate intake contributes to tumor
      formation in this model, we characterized gene expression signatures in tumors. A
      total of 175 probe sets had altered expression, with the majority (173) showing
      increased expression compared with normal intestine. Functional categorization
      revealed that most genes were involved in cancer (51 genes) or cell death (37
      genes); 31 genes appeared in both categories. Because apoptosis resistance is a
      hallmark of neoplasia, we assessed apoptosis in normal intestine of mice fed
      control (CD) and low-folate diets (FD); apoptosis was reduced in FD normal
      intestine compared with CD intestine by active caspase-3 expression (P = 0.027)
      and caspase-3/7 activities (P = 0.059). We selected candidate genes with
      antiapoptotic properties that had increased expression in tumor microarrays,
      CD44, and gelsolin and confirmed these increases at the mRNA and protein levels.
      CD44 and gelsolin protein also increased in mice fed the FD compared with the CD,
      normal intestine. Bcl-2-like 1:Bcl-2-antagonist/killer 1 mRNA ratios tended to be
      greater in FD than in CD normal intestine (P = 0.056). In conclusion, tumors
      induced by low dietary folate exhibited gene expression profiles that are
      characteristic of disrupted apoptosis. Folate depletion in normal intestine may
      trigger neoplasia through increased DNA damage and defective apoptosis;
      upregulation of CD44 and gelsolin, and the mitochondrial apoptotic pathway are
      implicated.

PMID- 19176748
TI  - Sugar and fat bingeing have notable differences in addictive-like behavior.
AB  - Ingestion of different nutrients, such as fats and sugars, normally produces
      different effects on physiology, the brain, and behavior. However, they do share
      certain neural pathways for reinforcement of behavior, including the mesolimbic
      dopamine (DA) system. When these nutrients are consumed in the form of binges,
      this can release excessive DA, which causes compensatory changes that are
      comparable to the effects of drugs of abuse. In this article, we review data
      obtained with animal models of fat and sugar bingeing. The concept of "food
      addiction" is described and reviewed from both clinical and laboratory animal
      perspectives. Behavioral manifestations of addictive-like behavior and
      concomitant alterations in DA and opioid systems are compared for sugar and fat
      bingeing. Finally, in relation to eating disorders and obesity, we discuss how
      fat may be the macronutrient that results in excess body weight, and sweet taste
      in the absence of fat may be largely responsible for producing addictive-like
      behaviors that include a withdrawal syndrome.

PMID- 19176750
TI  - Symposium overview--Food addiction: fact or fiction?
AB  - Food addiction is a pervasive, yet controversial, topic that has gained recent
      attention in both lay media and the scientific literature. The goal of this
      series of articles is to use a combination of preclinical and clinical data to
      determine whether foods, like drugs of abuse, can be addictive, the conditions
      under which the addiction develops, and the underlying neurophysiological
      substrates. Operational definitions of addiction that have been used in the
      treatment of human disorders and to guide research in both humans and animals are
      presented, and an overview of the symposium articles is provided. We propose that
      specific foods, especially those that are rich in fat and/or sugar, are capable
      of promoting "addiction"-like behavior and neuronal change under certain
      conditions. That is, these foods, although highly palatable, are not addictive
      per se but become so following a restriction/binge pattern of consumption. Such
      consummatory patterns have been associated with increased risk for comorbid
      conditions such as obesity, early weight gain, depression, anxiety, and substance
      abuse as well as with relapse and treatment challenges. The topic of food
      addiction bears study, therefore, to develop fresh approaches to clinical
      intervention and to advance our understanding of basic mechanisms involved in
      loss of control.

PMID- 19176751
TI  - Salt inactivates endothelial nitric oxide synthase in endothelial cells.
AB  - There is a 1-4 mmol/L rise in plasma sodium concentrations in individuals with
      high salt intake and in patients with essential hypertension. In this study, we
      used 3 independent assays to determine whether such a small increase in sodium
      concentrations per se alters endothelial nitric oxide synthase (eNOS) function
      and contributes to hypertension. By directly measuring NOS activity in living
      bovine aortic endothelial cells, we demonstrated that a 5-mmol/L increase in salt
      concentration (from 137 to 142 mmol/L) caused a 25% decrease in NOS activity.
      Importantly, the decrease in NOS activity was in a salt concentration-dependent
      manner. The NOS activity was decreased by 25, 45, and 70%, with the increase of
      5, 10, and 20 mmol/L of NaCl, respectively. Using Chinese hamster ovary cells
      stably expressing eNOS, we confirmed the inhibitory effects of salt on eNOS
      activity. The eNOS activity was unaffected in the presence of equal milliosmol of
      mannitol, which excludes an osmotic effect. Using an ex vivo aortic angiogenesis
      assay, we demonstrated that salt attenuated the nitric oxide (NO)-dependent
      proliferation of endothelial cells. By directly monitoring blood pressure changes
      in response to salt infusion, we found that in vivo infusion of salt induced an
      acute increase in blood pressure in a salt concentration-dependent manner. In
      conclusion, our findings demonstrated that eNOS is sensitive to changes in salt
      concentration. A 5-mmol/L rise in salt concentration, within the range observed
      in essential hypertension patients or in individuals with high salt intake, could
      significantly suppress eNOS activity. This salt-induced reduction in NO
      generation in endothelial cells may contribute to the development of
      hypertension.

PMID- 19176752
TI  - Osteoclastogenesis by bone marrow-derived macrophages is enhanced in obese mice.
AB  - Obesity induces a low-grade systemic chronic inflammatory condition for which
      macrophages are responsible. We hypothesized that obesity affects
      osteoclastogenesis by acting on bone marrow-derived macrophages (BMM). Male mice
      were fed a high-fat diet (45% of energy) or a standard diet (10% of energy) for
      13 wk. We found that the density of the femurs of obese mice was significantly
      lower than that of the femurs of lean mice. Osteoclastogenesis was enhanced in
      the BMM from obese mice. Lower levels of interleukin (IL)-10 were generated by
      the BMM from obese mice than by those from lean mice upon stimulation of receptor
      activator of nuclear factor-kappaB ligand. Neutralization of IL-10 in the BMM
      from obese mice was not as effective in increasing osteoclast (OC) formation as
      that in those from lean mice. Exogenous IL-10 inhibited OC formation more
      strongly in the BMM from obese mice than those from lean mice. The elevated level
      of OC formation in the BMM from obese mice may thus be due to in part to the
      lower level of IL-10, a negative regulator of osteoclastogenesis. Our results
      suggest that obesity is associated with bone loss via enhanced osteoclastogenesis
      due to reduced IL-10 production by the BMM from obese mice.

PMID- 19176753
TI  - Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate
      Rap1A, regulate beta1 integrin levels, and enhance cell migration.
AB  - Junctional adhesion molecule-A (JAM-A) is a transmembrane tight junction protein
      that has been shown to regulate barrier function and cell migration through
      incompletely understood mechanisms. We have previously demonstrated that JAM-A
      regulates cell migration by dimerization of the membrane-distal immunoglobulin
      like loop and a C-terminal postsynaptic density 95/disc-large/zona occludens
      (PDZ) binding motif. Disruption of dimerization resulted in decreased epithelial
      cell migration secondary to diminished levels of beta1 integrin and active Rap1.
      Here, we report that JAM-A is physically and functionally associated with the PDZ
      domain-containing molecules Afadin and PDZ-guanine nucleotide exchange factor
      (GEF) 2, but not zonula occludens (ZO)-1, in epithelial cells, and these
      interactions mediate outside-in signaling events. Both Afadin and PDZ-GEF2
      colocalized and coimmunoprecipitated with JAM-A. Furthermore, association of PDZ
      GEF2 with Afadin was dependent on the expression of JAM-A. Loss of JAM-A, Afadin,
      or PDZ-GEF2, but not ZO-1 or PDZ-GEF1, similarly decreased cellular levels of
      activated Rap1, beta1 integrin protein, and epithelial cell migration. The
      functional effects observed were secondary to decreased levels of Rap1A because
      knockdown of Rap1A, but not Rap1B, resulted in decreased beta1 integrin levels
      and reduced cell migration. These findings suggest that JAM-A dimerization
      facilitates formation of a complex with Afadin and PDZ-GEF2 that activates Rap1A,
      which regulates beta1 integrin levels and cell migration.

PMID- 19176754
TI  - Cooperative assembly and misfolding of CFTR domains in vivo.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) architecture
      consists of two membrane spanning domains (MSD1 and -2), two nucleotide binding
      domains (NBD1 and -2), and a regulatory (R) domain. Several point mutations lead
      to the channel misprocessing, with limited structural perturbation of the mutant
      domain. To gain more insight into the basis of CFTR folding defect, the
      contribution of domain-wise and cooperative domain folding was assessed by
      determining 1) the minimal domain combination that is recognized as native and
      can efficiently escape the endoplasmic reticulum (ER) retention and 2) the impact
      of mutation on the conformational coupling among domains. One-, two-, three-, and
      most of the four-domain assemblies were retained at the ER. Solubilization
      mutations, however, rescued the NBD1 processing defect conceivably by
      thermodynamic stabilization. The smallest folding unit that traversed the
      secretory pathway was composed of MSD1-NBD1-R-MSD2 as a linear or split
      polypeptide. Cystic fibrosis-causing missense mutations in the MSD1, NBD1, MSD2,
      and NBD2 caused conformational defect in multiple domains. We propose that
      cooperative posttranslational folding is required for domain stabilization and
      provides a plausible explanation for the global misfolding caused by point
      mutations dispersed along the full-length CFTR.

PMID- 19176756
TI  - Illinois trauma centers and intimate partner violence: are we doing our share?
AB  - Intimate partner violence (IPV) is a major source of morbidity and mortality
      nationally. Trauma Centers can be very helpful for victims of IPV but there may
      be variability in IPV resource provision. A survey was mailed to each of the 65
      Trauma Centers in Illinois. Stata and EZ-Text statistical software were used for
      analysis. Eighty-three percent of trauma centers returned the survey. Ninety
      percent of respondents had an IPV screening policy. All but one Center reported
      having IPV services available, including social work (93%) and 24 hour/day IPV
      teams (7%). Most Centers felt their IPV services were adequate (69%), but 22%
      felt services were inadequate, particularly resource availability. Trauma Centers
      in the state of Illinois are generally succeeding at screening for IPV. However,
      there is lack of uniformity with respect to screening and services, suggesting
      that there is room for improvement.

PMID- 19176755
TI  - USP9X enhances the polarity and self-renewal of embryonic stem cell-derived
      neural progenitors.
AB  - The substrate-specific deubiquitylating enzyme USP9X is a putative "stemness"
      gene expressed in many progenitor cell populations. To test its function in
      embryonic stem cell-derived neural progenitor/stem cells, we expressed USP9X from
      a Nestin promoter. Elevated USP9X levels resulted in two phenomena. First, it
      produced a dramatically altered cellular architecture wherein the majority (>80%)
      of neural progenitors was arranged into radial clusters. These progenitors
      expressed markers of radial glial cells and were highly polarized with adherens
      junction proteins (N-cadherin, beta-catenin, and AF-6) and apical markers
      (Prominin1, atypical protein kinase C-zeta) as well as Notch, Numb, and USP9X
      itself, concentrated at the center. The cluster centers were also devoid of
      nuclei and so resembled the apical end-feet of radial progenitors in the neural
      tube. Second, USP9X overexpression caused a fivefold increase in the number of
      radial progenitors and neurons, in the absence of exogenous growth factors. 5
      Bromo-2'-deoxyuridine labeling, as well as the examination of the brain lipid
      binding protein:betaIII-tubulin ratio, indicated that nestin-USP9X enhanced the
      self-renewal of radial progenitors but did not block their subsequent
      differentiation to neurons and astrocytes. nestin-USP9X radial progenitors
      reformed clusters after passage as single cells, whereas control cells did not,
      suggesting it aids the establishment of polarity. We propose that USP9X-induced
      polarization of these neural progenitors results in their radial arrangement,
      which provides an environment conducive for self-renewal.

PMID- 19176757
TI  - Polyamines regulate E-cadherin transcription through c-Myc modulating intestinal
      epithelial barrier function.
AB  - The integrity of the intestinal epithelial barrier depends on intercellular
      junctions that are highly regulated by numerous extracellular and intracellular
      factors. E-cadherin is found primarily at the adherens junctions in the
      intestinal mucosa and mediates strong cell-cell contacts that have a functional
      role in forming and regulating the epithelial barrier. Polyamines are necessary
      for E-cadherin expression, but the exact mechanism underlying polyamines remains
      elusive. The current study was performed to determine whether polyamines induce E
      cadherin expression through the transcription factor c-Myc and whether polyamine
      regulated E-cadherin plays a role in maintenance of the epithelial barrier
      integrity. Decreasing cellular polyamines reduced c-Myc and repressed E-cadherin
      transcription as indicated by a decrease in levels of E-cadherin promoter
      activity and its mRNA. Forced expression of the c-myc gene by infection with
      adenoviral vector containing c-Myc cDNA stimulated E-cadherin promoter activity
      and increased E-cadherin mRNA and protein levels in polyamine-deficient cells.
      Experiments using different E-cadherin promoter mutants revealed that induction
      of E-cadherin transcription by c-Myc was mediated through the E-Pal box located
      at the proximal region of the E-cadherin promoter. Decreased levels of E-cadherin
      in polyamine-deficient cells marginally increased basal levels of paracellular
      permeability but, remarkably, potentiated H(2)O(2)-induced epithelial barrier
      dysfunction. E-cadherin silencing by transfection with its specific small
      interfering RNA also increased vulnerability of the epithelial barrier to
      H(2)O(2). These results indicate that polyamines enhance E-cadherin transcription
      by activating c-Myc, thus promoting function of the epithelial barrier.

PMID- 19176758
TI  - Dynamics of neutrophil extravasation and vascular permeability are uncoupled
      during aseptic cutaneous wounding.
AB  - Transport of macromolecules and transmigration of leukocytes across vascular
      endothelium are regulated by a tight molecular junction, but the mechanisms by
      which these two inflammatory events are differentially controlled in time and
      magnitude during aseptic cutaneous wounding remain elusive. A real-time
      fluorescence imaging technique was developed to simultaneously track influx of
      Alexa 680-labeled albumin and genetically tagged enhanced green fluorescent
      protein-neutrophils [polymorphonuclear neutrophils (PMN)] within the wound bed.
      Vascular permeability increased approximately threefold more rapidly than the
      rate of PMN influx, reaching a maximum at 12 h, on the order of approximately
      0.15% per minute versus approximately 0.05% per minute for PMN influx, which
      peaked at 18 h. Systemic depletion of PMN with antibody blocked their
      extravasation to the wound but did not alter the increase in vascular
      permeability. In contrast, pretreatment with antiplatelet GPIb decreased
      permeability by 25% and PMN influx by 50%. Hyperpermeability stimulated by the
      endothelium-specific agonists VEGF or thrombin at 24 h postwounding was
      completely inhibited by blocking Rho-kinase-dependent signaling, whereas less
      inhibition was observed at 1 h and neutrophil influx was not perturbed. These
      data suggest that in aseptic wounds, the endothelium maintains a tight junctional
      barrier to protein leakage that is independent of neutrophil transmigration,
      partially dependent on circulating platelets, and associated with Rho-kinase
      dependent signaling.

PMID- 19176759
TI  - Vascular endothelial growth factor induces protein kinase D-dependent production
      of proinflammatory cytokines in endothelial cells.
AB  - Emerging evidence indicates that vascular endothelial growth factor (VEGF) plays
      a critical role in host inflammatory responses in several disease states,
      including atherosclerosis, sepsis, and rheumatoid arthritis. In this study, we
      determined the effect of VEGF on endothelial induction of proinflammatory
      cytokines and investigated the responsible signal pathways. By using a cytokine
      antibody array that detects the end point protein products released from
      endothelial cells (ECs), we found that VEGF, via VEGF receptor 2 (VEGFR2),
      predominantly induced the production of proinflammatory cytokine interleukin (IL)
      6 and CXC chemokines IL-8 and growth-related oncogene-alpha (GRO-alpha) in ECs
      but not in leukocytes among 36 cytokines in the array. The production of these
      inflammatory cytokines by VEGF was much stronger than the induction of cell
      adhesion molecule in ECs. We further found that the cytokine production by VEGF
      was essentially mediated by the Go-6976-sensitive protein kinase D (PKD) family
      kinases. Importantly, the VEGF-induced production of IL-6, IL-8, and GRO-alpha
      was inhibited approximately 70%, 40%, or 37% by PKD1 silencing (more than 90%
      knockdown) with three small interference RNAs that target different PKD1 regions.
      Moreover, silencing PKD2 downregulated VEGFR2 and markedly inhibited the cytokine
      production by VEGF in ECs. Our results indicate that VEGF, via VEGFR2-PKD1 axis,
      induces the production of proinflammatory cytokine IL-6, IL-8, and GRO-alpha in
      ECs but not in leukocytes, which may offer new insights into the mechanism of the
      proinflammatory activity of VEGF.

PMID- 19176761
TI  - Ca2+ pathway involved in the refilling of store sites in rat adrenal medullary
      cells.
AB  - It has been suggested that store-operated Ca(2+) entry (SOC) facilitates
      catecholamine secretion and synthesis in bovine adrenal medullary (AM) cells.
      However, there has been no experimental result clearly showing that cation
      channel activity is enhanced by store Ca(2+) depletion. Thus the present
      experiments were undertaken to address the issue of whether rat AM cells have SOC
      channels. Inhibition of the sarco(endo)plasmic reticulum Ca(2+) (SERCA) pump
      resulted in a sustained increase in intracellular Ca(2+) concentration
      ([Ca(2+)](i)) in rat AM cells. This increase was completely suppressed by 2 mM
      Ni(2+) but not by 100 muM D600. A bath application of Ni(2+), but not D600,
      produced an outward current at -60 mV in rat AM cells, whereas exposure to a
      SERCA pump inhibitor did not affect either the whole cell current level or the
      Ni(2+)-induced outward current. The refilling of intracellular store sites was
      suppressed by the addition of Ni(2+) to the perfusate. RT-PCR revealed that
      transcripts for transient receptor potential channels 1 (TRPC1) and 5 (TRPC5)
      were present in rat adrenal medullas. Immunocytochemistry showed that TRPC1
      channels, which have been implicated in SOC in certain types of cells, were
      mainly localized in the endoplasmic reticulum (ER) and not in the plasma
      membrane, and that STIM1, a Ca(2+) sensor in the ER, was not expressed in rat AM
      cells. On the basis of these results, we conclude that rat AM cells lack the SOC
      mechanism.

PMID- 19176760
TI  - Counterregulation of clathrin-mediated endocytosis by the actin and microtubular
      cytoskeleton in human neutrophils.
AB  - We have recently reported that disruption of the actin cytoskeleton enhanced N
      formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated granule exocytosis in
      human neutrophils but decreased plasma membrane expression of complement receptor
      1 (CR1), a marker of secretory vesicles. The present study was initiated to
      determine if reduced CR1 expression was due to fMLP-stimulated endocytosis, to
      determine the mechanism of this endocytosis, and to examine its impact on
      neutrophil functional responses. Stimulation of neutrophils with fMLP or
      ionomycin in the presence of latrunculin A resulted in the uptake of Alexa fluor
      488-labeled albumin and transferrin and reduced plasma membrane expression of
      CR1. These effects were prevented by preincubation of the cells with sucrose,
      chlorpromazine, or monodansylcadaverine (MDC), inhibitors of clathrin-mediated
      endocytosis. Sucrose, chlorpromazine, and MDC also significantly inhibited fMLP-
      and ionomycin-stimulated specific and azurophil granule exocytosis. Disruption of
      microtubules with nocodazole inhibited endocytosis and azurophil granule
      exocytosis stimulated by fMLP in the presence of latrunculin A. Pharmacological
      inhibition of phosphatidylinositol 3-kinase, ERK1/2, and PKC significantly
      reduced fMLP-stimulated transferrin uptake in the presence of latrunculin A.
      Blockade of clathrin-mediated endocytosis had no significant effect on fMLP
      stimulated phosphorylation of ERK1/2 in neutrophils pretreated with latrunculin
      A. From these data, we conclude that the actin cytoskeleton functions to limit
      microtubule-dependent, clathrin-mediated endocytosis in stimulated human
      neutrophils. The limitation of clathrin-mediated endocytosis by actin regulates
      the extent of both specific and azurophilic granule exocytosis.

PMID- 19176764
TI  - Complementary medicines in mental health.

PMID- 19176763
TI  - Green tea (-)-epigallocatechin gallate inhibits insulin stimulation of 3T3-L1
      preadipocyte mitogenesis via the 67-kDa laminin receptor pathway.
AB  - Insulin and (-)-epigallocatechin gallate (EGCG) have been reported to regulate
      fat cell mitogenesis and adipogenesis, respectively. This study investigated the
      pathways involved in EGCG modulation of insulin-stimulated mitogenesis in 3T3-L1
      preadipocytes. EGCG inhibited insulin stimulation of preadipocyte proliferation
      in a dose- and time-dependent manner. EGCG also suppressed insulin-stimulated
      phosphorylation of the insulin receptor-beta, insulin receptor (IR) substrates 1
      and 2 (IRS1 and IRS2), and mitogen-activated protein kinase pathway proteins,
      RAF1, MEK1/2, and ERK1/2, but not JNK. Furthermore, EGCG inhibited the
      association of IR with the IRS1 and IRS2 proteins, but not with the IRS4 protein.
      These data suggest that EGCG selectively affects particular types of IRS and MAPK
      family members. Generally, EGCG was more effective than epicatechin, epicatechin
      gallate, and epigallocatechin in modulating insulin-stimulated mitogenic
      signaling. We identified the EGCG receptor [also known as the 67-kDa laminin
      receptor (67LR)] in fat cells and found that its expression was sensitive to
      growth phase, tissue type, and differentiation state. Pretreatment of
      preadipocytes with 67LR antiserum prevented the effects of EGCG on insulin
      stimulated phosphorylation of IRS2, RAF1, and ERK1/2 and insulin-stimulated
      preadipocyte proliferation (cell number and bromodeoxyuridine incorporation).
      Moreover, EGCG tended to increase insulin-stimulated associations between the
      67LR and IR, IRS1, IRS2, and IRS4 proteins. These data suggest that EGCG mediates
      anti-insulin signaling in preadipocyte mitogenesis via the 67LR pathway.

PMID- 19176765
TI  - Web matters.

PMID- 19176762
TI  - The role of cell cholesterol and the cytoskeleton in the interaction between IK1
      and maxi-K channels.
AB  - Recently, we demonstrated a novel interaction between large-conductance (maxi-K
      or K(Ca)1.1) and intermediate-conductance (IK1 or K(Ca)3.1) Ca(2+)-activated K
      channels: activation of IK1 channels causes the inhibition of maxi-K activity
      (Thompson J and Begenisich T. J Gen Physiol 127: 159-169, 2006). Here we show
      that the interaction between these two channels can be regulated by the membrane
      cholesterol level in parotid acinar cells. Depletion of cholesterol using methyl
      beta-cyclodextrin weakened, while cholesterol enrichment increased, the ability
      of IK1 activation to inhibit maxi-K channels. Cholesterol's stereoisomer,
      epicholesterol, was unable to substitute for cholesterol in the interaction
      between the two K channels, suggesting a specific cholesterol-protein
      interaction. This suggestion was strengthened by the results of experiments in
      which cholesterol was replaced by coprostanol and epicoprostanol. These two
      sterols have nearly identical effects on membrane physical properties and
      cholesterol-rich microdomain stability, but had very different effects on the
      IK1/maxi-K interaction. In addition, the IK1/maxi-K interaction was unaltered in
      cells lacking caveolin, the protein essential for formation and stability of
      caveolae. Finally, disruption of the actin cytoskeleton restored the IK1-induced
      maxi-K inhibition that was lost with cell cholesterol depletion, demonstrating
      the importance of an intact cytoskeleton for the cholesterol-dependent regulation
      of the IK1/maxi-K interaction.

PMID- 19176767
TI  - Developing depression after a myocardial infarction increases risk of cardiac
      mortality but pre-existing depression does not.

PMID- 19176768
TI  - A nurse delivered management programme for depression in people with cancer
      reduces depressive symptoms compared with usual care.

PMID- 19176769
TI  - Escitalopram and problem solving therapy reduce the incidence of post-stroke
      depression.

PMID- 19176770
TI  - Review: antidepressants are of limited efficacy in juvenile depression.

PMID- 19176771
TI  - Review: insufficient evidence to guide use of drugs for clozapine induced
      hypersalivation.

PMID- 19176772
TI  - Antipsychotic medications do not differ substantially in ability to reduce
      violent behaviour in people with schizophrenia.

PMID- 19176773
TI  - CBT does not improve relapse rates in people with recently relapsed psychosis.

PMID- 19176774
TI  - Review: adding psychosocial interventions to pharmacotherapy for opioid
      detoxification improves outcomes.

PMID- 19176775
TI  - Review: CBT reduces fatigue in adults with chronic fatigue syndrome but effects
      at follow-up unclear.

PMID- 19176776
TI  - Exposure and ritual prevention reduces symptoms more than stress management
      training in OCD treated with SSRIs.

PMID- 19176777
TI  - Review: methylphenidate and psychosocial treatments either alone or in
      combination reduce ADHD symptoms.

PMID- 19176778
TI  - Osmotically released methylphenidate is more effective than atomoxetine in
      children and adolescents with ADHD.

PMID- 19176779
TI  - Atypical antipsychotics fail to improve functioning or quality of life in people
      with Alzheimer's disease.

PMID- 19176780
TI  - Dimebon improves cognitive function in people with mild to moderate Alzheimer's
      disease.

PMID- 19176781
TI  - Elderly women with larger social networks are less likely to develop dementia.

PMID- 19176782
TI  - Short term use of antipsychotics increases the risk of serious adverse events in
      elderly people with dementia.

PMID- 19176783
TI  - Bidirectional association between elevated depressive symptoms and type 2
      diabetes.

PMID- 19176784
TI  - Varying effects of psychotropic medications on fracture risk in older people.

PMID- 19176785
TI  - Current use of SSRIs and tricyclic antidepressants may increase the risk of non
      vertebral fractures in the elderly.

PMID- 19176786
TI  - Prolonged exposure to SRIs during pregnancy increases risks of adverse neonatal
      outcomes.

PMID- 19176787
TI  - Antidepressant use during first trimester not associated with risk of major
      congenital malformations.

PMID- 19176788
TI  - Maternal use of antipsychotics in early pregnancy: little evidence of increased
      risk of congenital malformations.

PMID- 19176789
TI  - Antipsychotic prescriptions for children and adolescents in the UK increased from
      1993 to 2005.

PMID- 19176790
TI  - People admitted to psychiatric hospitals commonly lack the mental capacity to
      make treatment decisions.

PMID- 19176791
TI  - Multiple whole-genome alignments without a reference organism.
AB  - Multiple sequence alignments have become one of the most commonly used resources
      in genomics research. Most algorithms for multiple alignment of whole genomes
      rely either on a reference genome, against which all of the other sequences are
      laid out, or require a one-to-one mapping between the nucleotides of the genomes,
      preventing the alignment of recently duplicated regions. Both approaches have
      drawbacks for whole-genome comparisons. In this paper we present a novel
      symmetric alignment algorithm. The resulting alignments not only represent all of
      the genomes equally well, but also include all relevant duplications that
      occurred since the divergence from the last common ancestor. Our algorithm,
      implemented as a part of the VISTA Genome Pipeline (VGP), was used to align seven
      vertebrate and six Drosophila genomes. The resulting whole-genome alignments
      demonstrate a higher sensitivity and specificity than the pairwise alignments
      previously available through the VGP and have higher exon alignment accuracy than
      comparable public whole-genome alignments. Of the multiple alignment methods
      tested, ours performed the best at aligning genes from multigene families-perhaps
      the most challenging test for whole-genome alignments. Our whole-genome multiple
      alignments are available through the VISTA Browser at
      http://genome.lbl.gov/vista/index.shtml.

PMID- 19176792
TI  - Bone-vascular axis in chronic kidney disease: a reality?

PMID- 19176793
TI  - Incidence, predictors, and associated outcomes of prostatism after kidney
      transplantation.
AB  - BACKGROUND AND OBJECTIVES: Renal transplantation is increasingly performed in
      elderly patients, and the incidence of benign prostatic hyperplasia (BPH)
      increases with age. Anuric males on dialysis may have occult BPH and not develop
      obstructive symptoms until urine flow is restored after transplantation. If left
      untreated, BPH poses a risk for numerous complications, including acute urinary
      retention (AUR), recurrent urinary tract infections (UTI), and renal failure. The
      authors hypothesized that incident BPH after renal transplantation would
      adversely affect allograft survival. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Medicare claims for BPH, AUR, UTI, and prostate resection
      procedures (transurethral resection of the prostate; TURP) were assessed in a
      retrospective cohort of 23,622 adult male Medicare primary renal transplant
      recipients in the United States Renal Data System database who received
      transplants from 1 January 2000 to 31 July 2005 and followed through 31 December
      2005. RESULTS: The 3-yr incidence of BPH post-transplant was 9.7%. The incidences
      of AUR, UTI, and TURP after BPH diagnosis (up to 3 yr posttransplant) were 10.3%,
      6.5%, and 7.3% respectively, and each was significantly associated with BPH. Cox
      regression analysis showed that recipient age per year, later year of transplant,
      and dialysis vintage were associated with incident BPH. Using Cox nonproportional
      hazards regression, BPH was significantly associated with renal allograft loss
      (including death). CONCLUSIONS: BPH is common in males after renal transplant and
      is independently associated with AUR, UTI, and graft loss. It is unknown whether
      treatment of BPH, either medical or surgical, attenuates these risks.

PMID- 19176794
TI  - The costs and benefits of automatic estimated glomerular filtration rate
      reporting.
AB  - BACKGROUND AND OBJECTIVES: The prevalence of chronic kidney disease (CKD) has
      increased over the past two decades. The sensitivity of serum creatinine (sCr) to
      identify CKD is low. As a result, many healthcare centers report estimated GFR
      (eGFR) with routine blood work. The aim of this study was to determine the cost
      effectiveness of automatic eGFR reporting compared with reporting sCr alone.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A Markov model was designed to
      evaluate the cost-effectiveness of reporting eGFR compared with reporting sCr
      alone in a hypothetical cohort of 60-yr-old individuals undergoing annual blood
      chemistry testing over 18 yr. Paths and path probabilities were identical between
      the two arms, except for the sensitivity and specificity of eGFR and sCr to
      detect CKD. RESULTS: eGFR reporting was dominant with a cost/effectiveness ratio
      of $16,751/quality-adjusted life year (QALY) versus $16,779/QALY for sCr
      reporting. Monte Carlo microsimulations in a hypothetical cohort of 10,000
      patients demonstrated that over 18 yr, an average of 13 fewer deaths, 29 fewer
      ESRD events, and 11,348 more false positive CKD (FP-CKD) cases occurred with eGFR
      reporting. A sensitivity analysis revealed that decreasing the FP-CKD quality of
      life by > 2% rendered sCr reporting more cost-effective than eGFR reporting. If
      FP-CKD reduced quality of life by 5%, the incremental cost-effectiveness ratio
      for sCr reporting versus eGFR reporting would be $4367/QALY. CONCLUSION: A
      decision analysis suggests that reporting eGFR may be beneficial, but this
      limited benefit was reversed with virtually any reduction in quality of life
      caused by incorrect diagnosis of CKD.

PMID- 19176795
TI  - Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic
      kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) has recently assumed
      epidemic proportion, becoming a troubling emerging cause of morbidity, especially
      if it progresses to terminal stage (ESRD). The authors aimed to evaluate whether
      neutrophil gelatinase-associated lipocalin (NGAL), a novel specific biomarker of
      acute kidney injury, could predict the progression of CKD. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Serum and urinary NGAL levels, together with a
      series of putative progression factors, were evaluated in a cohort of 96 patients
      (mean age: 57 +/- 16 years) affected by nonterminal CKD (eGFR > or =15
      ml/min/1.73 m(2)) of various etiology. Progression of CKD, assessed as doubling
      of baseline serum creatinine and/or onset of ESRD, was evaluated during follow
      up. RESULTS: At baseline, both serum and urinary NGAL were inversely,
      independently, and closely related to eGFR. After a median follow-up of 18.5 mo
      (range 1.01 to 20), 31 patients (32%) reached the composite endpoint. At
      baseline, these patients were significantly older and showed increased serum
      creatinine, calcium-phosphate product, C-reactive protein, fibrinogen, daily
      proteinuria, and NGAL levels, whereas eGFR values were significantly lower.
      Univariate followed by multivariate Cox proportional hazard regression analysis
      showed that urinary NGAL and sNGAL predicted CKD progression independently of
      other potential confounders, including eGFR and age. CONCLUSION: In patients with
      CKD, NGAL closely reflects the entity of renal impairment and represents a strong
      and independent risk marker for progression of CKD.

PMID- 19176796
TI  - Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Intravenous iron is a key component of anemia
      management for chronic kidney disease (CKD). Ferumoxytol is a unique intravenous
      iron product that can be administered as a rapid injection in doses up to 510 mg.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a randomized, open-label,
      controlled, multicenter Phase 3 trial to evaluate the safety and efficacy of
      intravenous ferumoxytol compared with oral iron. Anemic patients with CKD stage
      5D on hemodialysis and on a stable erythropoiesis-stimulating agent regimen
      received either two injections of 510 mg of ferumoxytol within 7 d (n = 114) or
      200 mg elemental oral iron daily for 21 d (n = 116). The primary efficacy
      endpoint was the change in hemoglobin from baseline to day 35. Safety was closely
      monitored. RESULTS: Ferumoxytol resulted in a mean increase in hemoglobin of 1.02
      +/- 1.13 g/dl at day 35 compared with 0.46 +/- 1.06 g/dl with oral iron (P =
      0.0002). Twice as many ferumoxytol-treated patients than oral iron-treated
      patients achieved a > or =1 g/dl hemoglobin increase at day 35 (P = 0.0002).
      There was a greater mean increase in transferrin saturation (TSAT) with
      ferumoxytol compared with oral iron at day 35 (P < 0.0001). The larger hemoglobin
      increase after ferumoxytol compared with oral iron at day 35 persisted after
      adjustment for baseline hemoglobin, TSAT, and serum ferritin. Overall adverse
      event rates were comparable between groups. CONCLUSIONS: In patients on
      hemodialysis, rapid intravenous injection of 510 mg of ferumoxytol led to
      significantly greater hemoglobin increases compared with oral iron, with
      comparable tolerability.

PMID- 19176797
TI  - Recommendations for a clinical decision support for the management of individuals
      with chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Care for advanced CKD patients is suboptimal. CKD
      practice guidelines aim to close gaps in care, but making providers aware of
      guidelines is an ineffective implementation strategy. The Institute of Medicine
      has endorsed the use of clinical decision support (CDS) for implementing
      guidelines. The authors' objective was to identify the requirements of an optimal
      CDS system for CKD management. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS:
      The aims of this study expanded on those of previous work that used the
      facilitated process improvement (FPI) methodology. In FPI, an expert workgroup
      develops a set of quality improvement tools that can subsequently be utilized by
      practicing physicians. The authors conducted a discussion with a group of
      multidisciplinary experts to identify requirements for an optimal CDS system.
      RESULTS: The panel considered the process of patient identification and
      management, associated barriers, and elements by which CDS could address these
      barriers. The panel also discussed specific knowledge needs in the context of a
      typical scenario in which CDS would be used. Finally, the group developed a set
      of core requirements that will likely facilitate the implementation of a CDS
      system aimed at improving the management of any chronic medical condition.
      CONCLUSIONS: Considering the growing burden of CKD and the potential healthcare
      and resource impact of guideline implementation through CDS, the relevance of
      this systematic process, consistent with Institute of Medicine recommendations,
      cannot be understated. The requirements described in this report could serve as a
      basis for the design of a CKD-specific CDS.

PMID- 19176798
TI  - SV2 renders primed synaptic vesicles competent for Ca2+ -induced exocytosis.
AB  - Synaptic vesicle protein 2 (SV2), one of the first synaptic vesicle proteins
      identified, is characterized by multiple transmembrane regions that exhibit
      homology to sugar transporters, and by a highly glycosylated intravesicular
      sequence. Deletion of SV2 causes postnatal lethality in mice, primarily because
      of fulminant epilepsy. At the cellular level, deletion of SV2 impairs
      neurotransmitter release, but its function is unknown, and even the exact point
      at which release is affected in SV2-deleted synapses remains unclear. Using
      electrophysiological approaches, we now examine at what step in exocytosis the
      deletion of SV2 impairs release. Our data demonstrate that deletion of SV2
      produces a decrease in evoked synaptic responses without causing changes in mini
      frequency, mini amplitude, the readily releasable pool of vesicles, or the
      apparent Ca(2+) sensitivity of vesicle fusion. These findings indicate that a
      previously unidentified step may couple priming of synaptic vesicles to Ca(2+)
      triggering of fusion, and that SV2 acts in this step to render primed synaptic
      vesicles fully Ca(2+) responsive. To investigate the structural requirements for
      this function of SV2, we used rescue experiments. We demonstrate that conserved
      charged residues within the transmembrane regions and the intravesicular
      glycosylation of SV2 are required for its normal folding and trafficking. In
      contrast, the conserved putative synaptotagmin-binding sequence of SV2 is fully
      dispensable. Viewed together, these observations suggest that SV2 functions in a
      maturation step of primed vesicles that converts the vesicles into a Ca(2+)- and
      synaptotagmin-responsive state.

PMID- 19176799
TI  - Rapid activation of plasticity-associated gene transcription in hippocampal
      neurons provides a mechanism for encoding of one-trial experience.
AB  - The hippocampus is hypothesized to support rapid encoding of ongoing experience.
      A critical prerequisite for such function is the ability to readily recruit
      enduring synaptic plasticity in hippocampal neurons. Hippocampal long-term
      potentiation (LTP) and memory consolidation require expression of the immediate
      early gene (IEG) Arc. To determine whether Arc transcription could be driven by
      limited and controlled behavioral experience, we used a rectangular track
      paradigm. In past electrophysiological studies, pyramidal neurons recorded from
      rats running in one direction on similar tracks typically exhibited a single
      firing field. Using fluorescence in situ hybridization, we show that the
      behavioral activity associated with a single lap around the track was sufficient
      to trigger Arc transcription in complete CA3 neuronal ensembles, as predicted
      given the role of CA3 in one-trial learning. In contrast, Arc transcription in
      CA1 ensembles was recruited incrementally, with maximal activation achieved after
      four laps a day for 4 consecutive days. To test whether Arc transcription is
      linked to learning and plasticity, or merely elicited by location-specific
      firing, we inactivated the medial septum, a treatment that compromises
      hippocampus-dependent learning and LTP but spares location-specific firing in CA1
      neurons. Septal inactivation abolished track training-induced Arc transcription
      in CA1 and CA3 neurons, showing that Arc transcription requires plasticity
      inducing stimuli. Accordingly, LTP induction activated Arc transcription in CA1
      neurons in vivo. These findings demonstrate for the first time that a single
      brief experience, equivalent to a single crossing of a firing field, can trigger
      IEG expression required for long-term plasticity in the hippocampus.

PMID- 19176800
TI  - Modulation of the dimer interface at ionotropic glutamate-like receptor delta2 by
      D-serine and extracellular calcium.
AB  - GluRdelta2 is a member of the iGluR family, but despite a prominent role in
      cerebellar synaptic plasticity, this receptor does not appear to function as an
      ion channel. Endogenous ligands that modulate the activity of native GluRdelta2
      in the cerebellum have not been identified, but two candidate modulators are d
      serine and extracellular calcium. Taking advantage of known crystal structures
      and spontaneously active GluRdelta2 receptors containing the lurcher mutation
      (GluRdelta2(Lc)), we investigated the mechanism by which calcium and d-serine
      regulate the activity of GluRdelta2(Lc). Our data suggest that calcium binding
      stabilizes the dimer interface formed between two agonist-binding domains and
      increases GluRdelta2(Lc) currents. The data further suggest that d-serine binding
      induces rearrangements at the dimer interface to diminish GluRdelta2(Lc) currents
      by a mechanism that resembles desensitization at AMPA and kainate receptors.
      Thus, we propose that calcium and d-serine binding have opposing effects on the
      stability of the dimer interface. Furthermore, the effects of calcium are
      observed at concentrations that are within the physiological range, suggesting
      that the ability of native GluRdelta2 to respond to ligand binding may be
      modulated by extracellular calcium. These findings place GluRdelta2 among AMPA
      and kainate receptors, where the dimer interface is not only a biologically
      important site for functional regulation, but also an important target for
      exogenous and endogenous ligands that modulate receptor function.

PMID- 19176801
TI  - A novel nicotinic acetylcholine receptor subtype in basal forebrain cholinergic
      neurons with high sensitivity to amyloid peptides.
AB  - Nicotinic acetylcholine receptors (nAChRs) containing alpha7 subunits are thought
      to assemble as homomers. alpha7-nAChR function has been implicated in learning
      and memory, and alterations of alpha7-nAChR have been found in patients with
      Alzheimer's disease (AD). Here we report findings consistent with a novel,
      naturally occurring nAChR subtype in rodent, basal forebrain cholinergic neurons.
      In these cells, alpha7 subunits are coexpressed, colocalize, and coassemble with
      beta2 subunit(s). Compared with homomeric alpha7-nAChRs from ventral tegmental
      area neurons, functional, presumably heteromeric alpha7beta2-nAChRs on
      cholinergic neurons freshly dissociated from medial septum/diagonal band (MS/DB)
      exhibit relatively slow kinetics of whole-cell current responses to nicotinic
      agonists and are more sensitive to the beta2 subunit-containing nAChR-selective
      antagonist, dihydro-beta-erythroidine (DHbetaE). Interestingly, presumed,
      heteromeric alpha7beta2-nAChRs are highly sensitive to functional inhibition by
      pathologically relevant concentrations of oligomeric, but not monomeric or
      fibrillar, forms of amyloid beta(1-42) (Abeta(1-42)). Slow whole-cell current
      kinetics, sensitivity to DHbetaE, and specific antagonism by oligomeric Abeta(1
      42) also are characteristics of heteromeric alpha7beta2-nAChRs, but not of
      homomeric alpha7-nAChRs, heterologously expressed in Xenopus oocytes. Moreover,
      choline-induced currents have faster kinetics and less sensitivity to Abeta when
      elicited from MS/DB neurons derived from nAChR beta2 subunit knock-out mice
      rather than from wild-type mice. The presence of novel, functional, heteromeric
      alpha7beta2-nAChRs on basal forebrain cholinergic neurons and their high
      sensitivity to blockade by low concentrations of oligomeric Abeta(1-42) suggests
      possible mechanisms for deficits in cholinergic signaling that could occur early
      in the etiopathogenesis of AD and might be targeted by disease therapies.

PMID- 19176802
TI  - Medial temporal lobe activity during retrieval of semantic memory is related to
      the age of the memory.
AB  - We measured brain activity using event-related fMRI as participants recalled
      answers to 160 questions about news events that had occurred during the past 30
      years. Guided by earlier findings from patients with damage limited to the
      hippocampus who were given the same test material, we looked for regions that
      exhibited gradually decreasing activity as participants recalled memories from 1
      12 years ago and a constant level of activity during recall of more remote
      memories. Regions in the medial temporal lobe exhibited a decrease in brain
      activity in relation to the age of the memory (hippocampus, temporopolar cortex,
      and amygdala). Regions in the frontal lobe, temporal lobe, and parietal lobe
      exhibited the opposite pattern. The findings for all of these regions were
      unrelated to the richness of the memories, to how well test questions were
      remembered later (encoding for subsequent memory), nor to how frequently semantic
      memories were accompanied by personal, episodic recollections. Last, activity in
      a different group of regions (perirhinal cortex, parahippocampal cortex, and
      inferior temporal gyrus) was associated with how well the test questions were
      subsequently remembered. The results support the idea that medial temporal lobe
      structures play a time-limited role in semantic memory.

PMID- 19176804
TI  - The Drosophila BEACH family protein, blue cheese, links lysosomal axon transport
      with motor neuron degeneration.
AB  - Impaired axon transport is one of the earliest pathological manifestations of
      several neurodegenerative diseases, and mutations in motor proteins can
      exacerbate or cause degeneration (Williamson and Cleveland, 1999; Gunawardena and
      Goldstein, 2004; Stokin and Goldstein, 2006). Compromised function in lysosomes
      and other degradative organelles that intersect with the lysosomal pathway are
      also strongly implicated in neurodegenerative disease pathology (Nixon and
      Cataldo, 2006; Rubinsztein, 2006). However, any functional link between these two
      phenomena has not as yet been recognized. Drosophila mutants in blue cheese
      (bchs) undergo progressive brain degeneration as adults and have shortened life
      span (Finley et al., 2003), but the cellular function of Bchs and the cause of
      degeneration have not been identified. A role in lysosomal trafficking is
      suggested by the homology of Bchs with the vesicle trafficking-associated BEACH
      (Beige and Chediak-Higashi) domain protein family (Wang et al., 2002; De Lozanne,
      2003) and by its genetic interaction with a lysosomal transport pathway (Simonsen
      et al., 2007). Here, we describe the degeneration of a population of identified
      larval motor neurons in bchs mutants. We present evidence that Bchs is primarily
      lysosomal in those motor neurons in wild type and, using live fluorescence
      imaging of individual motor neurons in intact larvae, show that lysosomal
      vesicles fail to be transported toward motor neuron termini in bchs mutant and
      Bchs-overexpressing larvae. We suggest therefore that anterograde transport of
      lysosomes toward synaptic termini is a key factor in preventing motor neuron
      degeneration and that Bchs reveals a functional link between the lysosomal
      degradative pathway and transport.

PMID- 19176803
TI  - Role of ionotropic glutamate receptors in long-term potentiation in rat
      hippocampal CA1 oriens-lacunosum moleculare interneurons.
AB  - Some interneurons of the hippocampus exhibit NMDA receptor-independent long-term
      potentiation (LTP) that is induced by presynaptic glutamate release when the
      postsynaptic membrane potential is hyperpolarized. This "anti-Hebbian" form of
      LTP is prevented by postsynaptic depolarization or by blocking AMPA and kainate
      receptors. Although both AMPA and kainate receptors are expressed in hippocampal
      interneurons, their relative roles in anti-Hebbian LTP are not known. Because
      interneuron diversity potentially conceals simple rules underlying different
      forms of plasticity, we focus on glutamatergic synapses onto a subset of
      interneurons with dendrites in stratum oriens and a main ascending axon that
      projects to stratum lacunosum moleculare, the oriens-lacunosum moleculare (O-LM)
      cells. We show that anti-Hebbian LTP in O-LM interneurons has consistent
      induction and expression properties, and is prevented by selective inhibition of
      AMPA receptors. The majority of the ionotropic glutamatergic synaptic current in
      these cells is mediated by inwardly rectifying Ca(2+)-permeable AMPA receptors.
      Although GluR5-containing kainate receptors contribute to synaptic currents at
      high stimulus frequency, they are not required for LTP induction. Glutamatergic
      synapses on O-LM cells thus behave in a homogeneous manner and exhibit LTP
      dependent on Ca(2+)-permeable AMPA receptors.

PMID- 19176805
TI  - Subthreshold receptive field properties distinguish different classes of
      corticothalamic neurons in the somatosensory system.
AB  - Most corticothalamic (CT) neurons in somatosensory cortex are silent in lightly
      anesthetized and even awake animals, making it difficult to investigate CT
      function and the underlying circuitry. Here we use juxtasomal recording and
      stimulation techniques to probe subthreshold response properties of
      antidromically identified CT neurons in the rat whisker/barrel system. When
      neuronal firing is facilitated by depolarizing juxtasomal currents, silent
      neurons become responsive to whisker stimuli, permitting identification of three
      functional classes of CT cells: those having a short-latency excitatory response
      to whisker deflection, those having a long-latency response, and neurons whose
      firing is suppressed by whisker deflection. During sensorimotor behaviors when
      the CT system may be active, cells having excitatory vs inhibitory receptive
      fields may participate in push-pull corticothalamic circuits that, acting
      together, selectively enhance sensory signaling in the thalamocortical system.

PMID- 19176806
TI  - Reduction of spike afterdepolarization by increased leak conductance alters
      interspike interval variability.
AB  - Data from neurons in vivo have shown that spike output can often sustain episodes
      of high variability. Theoretical studies have indicated that the high conductance
      state of neurons brought on by synaptic activity can contribute to an increase in
      the variability of spike output by decreasing the integration timescale of the
      neuron. In the present work, we were interested in understanding how background
      synaptic conductance activity alters the interspike interval (ISI) variability of
      layer III pyramidal cells of the medial entorhinal cortex. We compared ISI
      variability in pyramidal cells as a result of synaptic current- or conductance
      mediated membrane fluctuations. We found that the effects of background synaptic
      conductance activity on ISI variability depend on the neuron type. In pyramidal
      cells lacking spike frequency adaptation, the variability increased in relation
      to a comparable synaptic current stimulus. In contrast, in pyramidal cells
      displaying spike frequency adaptation, the synaptic conductance stimulus produced
      lower ISI variability. To understand this result, we constructed a
      phenomenological model that reproduced the basic properties of these neurons
      under control and increased leak conductance. We found that leak can change the
      properties of the neuron by acting as a bifurcation parameter that reduces the
      afterdepolarization (ADP) and decreases the slope (gain) of the frequency-current
      relationship, particularly for transient stimuli. A lower gain with the added
      leak causes a reduction in ISI variability. We conclude that the ability of a
      high conductance state to increase ISI variability cannot be generalized and can
      depend on the spike ADP dynamics expressed by the neuron.

PMID- 19176807
TI  - Inhibition of monoamine oxidases desensitizes 5-HT1A autoreceptors and allows
      nicotine to induce a neurochemical and behavioral sensitization.
AB  - Although nicotine is generally considered to be the main compound responsible for
      addictive properties of tobacco, experimental data indicate that nicotine does
      not exhibit all the characteristics of other substances of abuse. We recently
      showed that a pretreatment with mixed irreversible monoamine oxidases inhibitors
      (MAOIs), such as tranylcypromine, triggers a locomotor response to nicotine in
      mice and allows maintenance of behavioral sensitization to nicotine in rats.
      Moreover, we showed by microdialysis in mice that behavioral sensitization
      induced by compounds belonging to main groups of drugs of abuse, such as
      amphetamine, cocaine, morphine, or alcohol, was underlain by sensitization of
      noradrenergic and serotonergic neurons. Here, this neurochemical sensitization
      was tested after nicotine, tranylcypromine, or a mixture of both compounds. Data
      indicate that, whereas neither repeated nicotine nor repeated tranylcypromine
      alone has any effect by itself, a repeated treatment with a mixture of nicotine
      and tranylcypromine induces both behavioral sensitization and sensitization of
      noradrenergic and serotonergic neurons. The development of neurochemical and
      behavioral sensitizations is blocked by prazosin and SR46349B [(1Z,2E)-1-(2
      fluoro-phenyl)-3-(4-hydroxyphenyl)-prop-2-en-one-O-(2-dimethylamino-ethyl)-oxime
      hemifumarate], two antagonists of alpha1b-adrenergic and 5-HT(2A) receptors,
      respectively, but not by SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl
      2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride], a D(1) receptor antagonist.
      Finally, we found that pretreatments with WAY 100635 [N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-(2-pyridinyl)cyclo-hexane carboxamide trihydrochloride], a 5
      HT(1A) receptor antagonist, can also induce a behavioral and neurochemical
      sensitization to repeated nicotine. Complementary experiments with 8-OHDPAT (8
      hydroxy-dipropylamino-tetralin), a 5-HT(1A) receptor agonist, and analysis of 5
      HT(1A) receptors expression in the dorsal raphe nucleus after a tranylcypromine
      injection indicate that MAOIs contained in tobacco desensitize 5-HT(1A)
      autoreceptors to trigger the strong addictive properties of tobacco.

PMID- 19176808
TI  - Morphine enhances microglial migration through modulation of P2X4 receptor
      signaling.
AB  - Opioids, although fundamental to the treatment of pain, are limited in efficacy
      by side effects including tolerance and hyperalgesia. Using an in vitro culture
      system, we report that morphine increased microglial migration via a novel
      interaction between mu-opioid and P2X(4) receptors, which is dependent upon
      PI3K/Akt pathway activation. Morphine at 100 nm enhanced migration of primary
      microglial cells toward adenosine diphosphate by 257, 247, 301, 394, and 345%
      following 2, 6, 12, 24, and 48 h of stimulation, respectively. This opioid
      dependent migration effect was inhibited by naloxone and confirmed to be mu
      opioid receptor-dependent through the use of selective agonists and antagonists.
      PPADS [pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid)], a P2X(1-3,5-7)
      antagonist, had no effect on microglial migration; however, TNP-ATP [2',3'-O
      (2,4,6-trinitrophenyl)-ATP], a P2X(1-7) antagonist, inhibited morphine-induced
      migration, suggesting a P2X(4) receptor-mediated effect. The PI3K inhibitors
      wortmannin and LY294002 decreased morphine-induced microglial migration. Iba1
      protein, a microglial marker, and P2X(4) receptor expression were significantly
      increased after 6, 12, 24, and 48 h of morphine stimulation. Together, these
      results provide evidence for two phases of morphine effects on microglia. The
      initial phase takes place in minutes, involves PI3K/Akt pathway activation and
      leads to acutely enhanced migration. The longer-term phase occurs on the order of
      hours and involves increased expression of Iba1 and P2X(4) receptor protein,
      which imparts a promigratory phenotype and is correlated with even greater
      migration. These data provide the first necessary step in supporting microglial
      migration as an attractive target for the prevention or attenuation of morphine
      induced side effects including tolerance and hyperalgesia.

PMID- 19176809
TI  - Dynamical response properties of neocortical neuron ensembles: multiplicative
      versus additive noise.
AB  - To understand the mechanisms of fast information processing in the brain, it is
      necessary to determine how rapidly populations of neurons can respond to incoming
      stimuli in a noisy environment. Recently, it has been shown experimentally that
      an ensemble of neocortical neurons can track a time-varying input current in the
      presence of additive correlated noise very fast, up to frequencies of several
      hundred hertz. Modulations in the firing rate of presynaptic neuron populations
      affect, however, not only the mean but also the variance of the synaptic input to
      postsynaptic cells. It has been argued that such modulations of the noise
      intensity (multiplicative modulation) can be tracked much faster than modulations
      of the mean input current (additive modulation). Here, we compare the response
      characteristics of an ensemble of neocortical neurons for both modulation
      schemes. We injected sinusoidally modulated noisy currents (additive and
      multiplicative modulation) into layer V pyramidal neurons of the rat
      somatosensory cortex and measured the trial and ensemble-averaged spike responses
      for a wide range of stimulus frequencies. For both modulation paradigms, we
      observed low-pass behavior. The cutoff frequencies were markedly high,
      considerably higher than the average firing rates. We demonstrate that
      modulations in the variance can be tracked significantly faster than modulations
      in the mean input. Extremely fast stimuli (up to 1 kHz) can be reliably tracked,
      provided the stimulus amplitudes are sufficiently high.

PMID- 19176810
TI  - The Parkinson disease protein leucine-rich repeat kinase 2 transduces death
      signals via Fas-associated protein with death domain and caspase-8 in a cellular
      model of neurodegeneration.
AB  - Neurodegenerative illnesses such as Parkinson and Alzheimer disease are an
      increasingly prevalent problem in aging societies, yet no therapies exist that
      retard or prevent neurodegeneration. Dominant missense mutations in leucine-rich
      repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson disease
      (PD), but the mechanisms by which mutant forms of LRRK2 disrupt neuronal function
      and cause cell death remain poorly understood. We report that LRRK2 interacts
      with the death adaptor Fas-associated protein with death domain (FADD), and that
      in primary neuronal culture LRRK2-mediated neurodegeneration is prevented by the
      functional inhibition of FADD or depletion of caspase-8, two key elements of the
      extrinsic cell death pathway. This pathway is activated by disease-triggering
      mutations, which enhance the LRRK2-FADD association and the consequent
      recruitment and activation of caspase-8. These results establish a direct
      molecular link between a mutant PD gene and the activation of programmed cell
      death signaling, and suggest that FADD/caspase-8 signaling contributes to LRRK2
      induced neuronal death.

PMID- 19176811
TI  - Synaptopodin regulates plasticity of dendritic spines in hippocampal neurons.
AB  - The spine apparatus is an essential component of dendritic spines of cortical and
      hippocampal neurons, yet its functions are still enigmatic. Synaptopodin (SP), an
      actin-binding protein, is tightly associated with the spine apparatus and it may
      play a role in synaptic plasticity, but it has not yet been linked
      mechanistically to synaptic functions. We studied endogenous and transfected SP
      in dendritic spines of cultured hippocampal neurons and found that spines
      containing SP generate larger responses to flash photolysis of caged glutamate
      than SP-negative ones. An NMDA-receptor-mediated chemical long-term potentiation
      caused the accumulation of GFP-GluR1 in spine heads of control but not of shRNA
      transfected, SP-deficient neurons. SP is linked to calcium stores, because their
      pharmacological blockade eliminated SP-related enhancement of glutamate
      responses, and release of calcium from stores produced an SP-dependent increase
      of GluR1 in spines. Thus, SP plays a crucial role in the calcium store-associated
      ability of neurons to undergo long-term plasticity.

PMID- 19176812
TI  - An auditory region in the primate insular cortex responding preferentially to
      vocal communication sounds.
AB  - Human imaging studies implicate the insular cortex in processing complex sounds
      and vocal communication signals such as speech. In addition, lesions of the
      insula often manifest as deficits in sound or speech recognition (auditory
      agnosia) and speech production. While models of acoustic perception assign an
      important role to the insula, little is known about the underlying neuronal
      substrate. Studying a vocal primate, we identified a predominantly auditory
      region in the caudal insula and therein discovered a neural representation of
      conspecific communication sounds. When probed with natural sounds, insula neurons
      exhibited higher response selectivity than neurons in auditory cortex, and in
      contrast to these, responded preferentially to conspecific vocalizations.
      Importantly, insula neurons not only preferred conspecific vocalizations over a
      wide range of environmental sounds and other animal vocalizations, but also over
      acoustically manipulated versions of these, demonstrating that this preference
      for vocalizations arises both from spectral and temporal features of the sounds.
      In addition, individual insula neurons responded highly selectively to only a few
      vocalizations and allowed the decoding of sound identity from single-trial
      responses. These findings characterize the caudal insula as a selectively
      responding auditory region, possibly part of a processing stream involved in the
      representation of communication sounds. Importantly, our results provide a neural
      counterpart for the human imaging and lesion findings and uncover a basis for a
      supposed role of the insula in processing vocal communication sounds such as
      speech.

PMID- 19176813
TI  - Appetitive and aversive taste conditioning in a computer game influences real
      world decision making and subsequent activation in insular cortex.
AB  - A stimulus, by virtue of its pairing with a rewarding or an aversive outcome, can
      acquire motivating properties reflecting that outcome. However, there is
      uncertainty concerning the extent to which such properties might be carried
      across contexts. In the current study we sought to determine whether conditioning
      dependent motivational properties can transfer from a computer game to the real
      world and, further, whether this conditioning might be expressed in terms of
      brain responses measured using functional magnetic resonance imaging (fMRI). We
      studied healthy participants conditioned with aversive and appetitive drinks in
      the context of a virtual cycling race. Three days after conditioning,
      participants returned for a fMRI session. We took this opportunity to observe the
      impact of incidental presentation of conditioned stimuli on a real-world decision
      (seat choice). We found a significant influence of conditioning on seat choice
      and, moreover, noted that individual susceptibility to this influence was
      reflected in differential insula cortex responses during subsequent scanning. The
      choice was also predicted by participants' personality scores and, as a
      statistical trend (p=0.07), by their sense of immersion in the game environment.
      Our data show that motivational properties of stimuli can transfer from the
      virtual to the real world. While much concern has been expressed over the impact
      of virtual experience on general levels of aggression and mood, our data point to
      another important consideration: the fact that a stimulus in the virtual
      environment can acquire motivational properties that persist and modify behavior
      in the real world.

PMID- 19176814
TI  - Working memory-related hippocampal deactivation interferes with long-term memory
      formation.
AB  - Previous findings indicate that the hippocampus does not only play a role in long
      term memory (LTM) encoding, but is important for working memory (WM) as well, in
      particular when multiple items are being processed. A recent study showed that
      maintenance of multiple items was associated with hippocampal activation
      (hippocampus-dependent WM), while maintenance of individual items induced
      hippocampal deactivations (hippocampus-independent WM). Here, we used two
      complimentary approaches to investigate whether WM-related activity patterns
      occur also during LTM encoding of sequentially presented items and whether they
      are related to the primacy effect, i.e., improved LTM encoding of items presented
      at the beginning of the list. Intracranial electroencephalogram in epilepsy
      patients and functional MRI in healthy subjects were recorded during a word-list
      learning task. As expected, the proportion of successfully encoded items was
      higher at the beginning of the list than at later list positions. Items at the
      beginning of the list which were subsequently forgotten were associated with
      negative blood oxygen level dependent responses and positive direct current
      slopes, corresponding to hippocampal deactivations, suggesting that they were not
      processed in hippocampus-dependent WM. These deactivations were absent for items
      later in the list and for subsequently remembered items. These data show that if
      processing of items at the beginning of the list is accompanied by hippocampal
      activity patterns previously observed during hippocampus-dependent WM, these
      items are subsequently remembered. However, deactivations of the hippocampus as
      previously observed during WM maintenance of individual items predicts failure of
      LTM encoding.

PMID- 19176815
TI  - Head direction cell activity in mice: robust directional signal depends on intact
      otolith organs.
AB  - The head direction (HD) cell signal is a representation of an animal's perceived
      directional heading with respect to its environment. This signal appears to
      originate in the vestibular system, which includes the semicircular canals and
      otolith organs. Preliminary studies indicate the semicircular canals provide a
      necessary component of the HD signal, but involvement of otolithic information in
      the HD signal has not been tested. The present study was designed to determine
      the otolithic contribution to the HD signal, as well as to compare HD cell
      activity of mice with that of rats. HD cell activity in the anterodorsal thalamus
      was assessed in wild-type C57BL/6J and otoconia-deficient tilted mice during
      locomotion within a cylinder containing a prominent visual landmark. HD cell
      firing properties in C57BL/6J mice were generally similar to those in rats.
      However, in C57BL/6J mice, landmark rotation failed to demonstrate dominant
      control of the HD signal in 36% of the sessions. In darkness, directional firing
      became unstable during 42% of the sessions, but landmark control was not
      associated with HD signal stability in darkness. HD cells were identified in
      tilted mice, but directional firing properties were not as robust as those of
      C57BL/6J mice. Most HD cells in tilted mice were controlled by landmark rotation
      but showed substantial signal degradation across trials. These results support
      current models that suggest otolithic information is involved in the perception
      of directional heading. Furthermore, compared with rats, the HD signal in mice
      appears to be less reliably anchored to prominent environmental cues.

PMID- 19176816
TI  - Early-stage waves in the retinal network emerge close to a critical state
      transition between local and global functional connectivity.
AB  - A novel, biophysically realistic model for early-stage, acetylcholine-mediated
      retinal waves is presented. In this model, neural excitability is regulated
      through a slow after-hyperpolarization (sAHP) operating on two different temporal
      scales. As a result, the simulated network exhibits competition between a
      desynchronizing effect of spontaneous, cell-intrinsic bursts, and the
      synchronizing effect of synaptic transmission during retinal waves. Cell
      intrinsic bursts decouple the retinal network through activation of the sAHP
      current, and we show that the network is capable of operating at a transition
      point between purely local and global functional connectedness, which corresponds
      to a percolation phase transition. Multielectrode array recordings show that, at
      this point, the properties of retinal waves are reliably predicted by the model.
      These results indicate that early spontaneous activity in the developing retina
      is regulated according to a very specific principle, which maximizes randomness
      and variability in the resulting activity patterns.

PMID- 19176817
TI  - Dramatically decreased cocaine self-administration in dopamine but not serotonin
      transporter knock-out mice.
AB  - There has been much interest in the relative importance of dopamine and serotonin
      transporters in the abuse-related-effects of cocaine. We tested the hypotheses
      that mice lacking the dopamine transporter (DAT(-/-)), the serotonin transporter
      (SERT(-/-)), or both (DAT(-/-)SERT(-/-)) exhibit decreased reinforcing effects of
      cocaine. We also assessed whether observed effects on self-administration are
      specific to cocaine or if operant behavior maintained by food or a direct
      dopamine agonist are similarly affected. We used a broad range of experimental
      conditions that included acquisition without previous training, behavior
      established with food training and subsequent testing with food, cocaine or a
      direct dopamine agonist as reinforcers, fixed ratio and progressive ratio
      schedules of reinforcement, and a reversal procedure. Wild-type mice readily
      acquired cocaine self-administration and showed dose-response curves
      characteristic of the schedule of reinforcement that was used. While some DAT(-/
      ) mice appeared to acquire cocaine self-administration transiently, almost all
      DAT(-/-) mice failed to self-administer cocaine reliably. Food-maintained
      behaviors were not decreased by the DAT mutation, and IV self-administration of a
      direct dopamine agonist was robust in the DAT(-/-) mice. In contrast to those
      mice, cocaine's reinforcing effects were not diminished in SERT(-/-) mice under
      any of the conditions tested, except for impaired initial acquisition of both
      food- and cocaine-maintained behavior. These findings support the notion that the
      DAT, but not the SERT, is critical in mediating the reinforcing effects of
      cocaine.

PMID- 19176818
TI  - The Rheb-mTOR pathway is upregulated in reactive astrocytes of the injured spinal
      cord.
AB  - Astrocytes in the CNS respond to tissue damage by becoming reactive. They
      migrate, undergo hypertrophy, and form a glial scar that inhibits axon
      regeneration. Therefore, limiting astrocytic responses represents a potential
      therapeutic strategy to improve functional recovery. It was recently shown that
      the epidermal growth factor (EGF) receptor is upregulated in astrocytes after
      injury and promotes their transformation into reactive astrocytes. Furthermore,
      EGF receptor inhibitors were shown to enhance axon regeneration in the injured
      optic nerve and promote recovery after spinal cord injury. However, the signaling
      pathways involved were not elucidated. Here we show that in cultures of adult
      spinal cord astrocytes EGF activates the mTOR pathway, a key regulator of
      astrocyte physiology. This occurs through Akt-mediated phosphorylation of the
      GTPase-activating protein Tuberin, which inhibits Tuberin's ability to inactivate
      the small GTPase Rheb. Indeed, we found that Rheb is required for EGF-dependent
      mTOR activation in spinal cord astrocytes, whereas the Ras-MAP kinase pathway
      does not appear to be involved. Moreover, astrocyte growth and EGF-dependent
      chemoattraction were inhibited by the mTOR-selective drug rapamycin. We also
      detected elevated levels of activated EGF receptor and mTOR signaling in reactive
      astrocytes in vivo in an ischemic model of spinal cord injury. Furthermore,
      increased Rheb expression likely contributes to mTOR activation in the injured
      spinal cord. Interestingly, injured rats treated with rapamycin showed reduced
      signs of reactive gliosis, suggesting that rapamycin could be used to harness
      astrocytic responses in the damaged nervous system to promote an environment more
      permissive to axon regeneration.

PMID- 19176819
TI  - Intracellular Zn2+ accumulation contributes to synaptic failure, mitochondrial
      depolarization, and cell death in an acute slice oxygen-glucose deprivation model
      of ischemia.
AB  - Despite considerable evidence for contributions of both Zn(2+) and Ca(2+) in
      ischemic brain damage, the relative importance of each cation to very early
      events in injury cascades is not well known. We examined Ca(2+) and Zn(2+)
      dynamics in hippocampal slices subjected to oxygen-glucose deprivation (OGD).
      When single CA1 pyramidal neurons were loaded via a patch pipette with a Ca(2+)
      sensitive indicator (fura-6F) and an ion-insensitive indicator (AlexaFluor-488),
      small dendritic fura-6F signals were noted after several (approximately 6-8)
      minutes of OGD, followed shortly by sharp somatic signals, which were attributed
      to Ca(2+) ("Ca(2+) deregulation"). At close to the time of Ca(2+) deregulation,
      neurons underwent a terminal increase in plasma membrane permeability, indicated
      by loss of AlexaFluor-488 fluorescence. In neurons coloaded with fura-6F and a
      Zn(2+)-selective indicator (FluoZin-3), progressive rises in cytosolic Zn(2+)
      levels were detected before Ca(2+) deregulation. Addition of the Zn(2+) chelator
      N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) significantly delayed
      both Ca(2+) deregulation and the plasma membrane permeability increases,
      indicating that Zn(2+) contributes to the degenerative signaling. Present
      observations further indicate that Zn(2+) is rapidly taken up into mitochondria,
      contributing to their early depolarization. Also, TPEN facilitated recovery of
      the mitochondrial membrane potential and of field EPSPs after transient OGD, and
      combined removal of Ca(2+) and Zn(2+) markedly extended the duration of OGD
      tolerated. These data provide new clues that Zn(2+) accumulates rapidly in
      neurons during slice OGD, is taken up by mitochondria, and contributes to
      consequent mitochondrial dysfunction, cessation of synaptic transmission, Ca(2+)
      deregulation, and cell death.

PMID- 19176821
TI  - Sustained in vivo inhibition of protein domains using single-chain Fv recombinant
      antibodies and its application to dissect RGMa activity on axonal outgrowth.
AB  - Antibodies are powerful tools for delineating the specific function of protein
      domains, yet several limitations restrict their in vivo applicability. Here we
      present a new method to obtain sustained in vivo inhibition of specific protein
      domains using recombinant antibodies. We show that long term in vivo expression
      of single-chain Fv (scFv) fragments in the developing CNS can be achieved through
      retroviral transduction. Moreover, specific scFvs generated against the N- and C
      terminal domains of the repulsive guidance molecule, RGMa, prevent proper axon
      targeting in the visual system. This work reveals a previously unappreciated role
      for the RGMa N-terminal domain in axon guidance, and provides a novel, broadly
      applicable and rapid procedure to functionally antagonize any protein domain in
      vivo.

PMID- 19176820
TI  - Neuropeptide Y fragments derived from neprilysin processing are neuroprotective
      in a transgenic model of Alzheimer's disease.
AB  - The endopeptidase neprilysin (NEP) is a major amyloid-beta (Abeta) degrading
      enzyme and has been implicated in the pathogenesis of Alzheimer's disease.
      Because NEP cleaves substrates other than Abeta, we investigated the potential
      role of NEP-mediated processing of neuropeptides in the mechanisms of
      neuroprotection in vivo. Overexpression of NEP at low levels in transgenic (tg)
      mice affected primarily the levels of neuropeptide Y (NPY) compared with other
      neuropeptides. Ex vivo and in vivo studies in tg mice and in mice that received
      lentiviral vector injections showed that NEP cleaved NPY into C-terminal
      fragments (CTFs), whereas silencing NEP reduced NPY processing. Immunoblot and
      mass spectrometry analysis showed that NPY 21-36 and 31-36 were the most abundant
      fragments generated by NEP activity in vivo. Infusion of these NPY CTFs into the
      brains of APP (amyloid precursor protein) tg mice ameliorated the
      neurodegenerative pathology in this model. Moreover, the amidated NPY CTFs
      protected human neuronal cultures from the neurotoxic effects of Abeta. This
      study supports the possibility that the NPY CTFs generated during NEP-mediated
      proteolysis might exert neuroprotective effects in vivo. This function of NEP
      represents a unique example of a proteolytic enzyme with dual action, namely,
      degradation of Abeta as well as processing of NPY.

PMID- 19176822
TI  - Genetic influences on sociability: heightened amygdala reactivity and event
      related responses to positive social stimuli in Williams syndrome.
AB  - Williams syndrome (WS) is a genetic disorder caused by a hemizygous microdeletion
      on chromosome 7q11.23. WS is associated with a compelling neurocognitive profile
      characterized by relative deficits in visuospatial function, relative strengths
      in face and language processing, and enhanced drive toward social engagement. We
      used a combined functional magnetic resonance imaging (fMRI) and event-related
      potential (ERP) approach to examine the neural basis of social responsiveness in
      WS participants to two types of social stimuli, negative (fearful) and positive
      (happy) emotional facial expressions. Here, we report a double dissociation
      consistent across both methods such that WS participants exhibited heightened
      amygdala reactivity to positive (happy) social stimuli and absent or attenuated
      amygdala reactivity to negative (fearful) social stimuli, compared with controls.
      The fMRI findings indicate that atypical social processing in WS may be rooted in
      altered development of disparate amygdalar nuclei that subserve different social
      functions. The ERP findings suggest that abnormal amygdala reactivity in WS may
      possibly function to increase attention to and encoding of happy expressions and
      to decrease arousal to fearful expressions. This study provides the first
      evidence that the genetic deletion associated with WS influences the function of
      the amygdala to be particularly responsive to socially appetitive stimuli.

PMID- 19176823
TI  - The contribution of synaptic inputs to sustained depolarizations in
      reticulospinal neurons.
AB  - Sensory stimulation elicits sustained depolarizations in lamprey reticulospinal
      (RS) cells for which intrinsic properties were shown to play a crucial role. The
      depolarizations last up to minutes, and we tested whether the intrinsic
      properties required the cooperation of synaptic inputs to maintain RS cells
      depolarized for such long periods of time. Ascending spinal inputs to RS cells
      were reversibly blocked by applying xylocaine over the rostral spinal cord
      segments. The duration of the sustained depolarizations was markedly reduced. The
      membrane potential oscillations in tune with locomotor activity that were present
      under control condition were also abolished. The contribution of excitatory
      glutamatergic inputs was then assessed by applying CNQX and AP-5 over one of two
      simultaneously recorded homologous RS cells on each side of the brainstem. The
      level of sensory-evoked depolarization decreased significantly in the cell
      exposed to the antagonists compared with the other RS cell monitored as a
      control. In contrast, local application of glycine only produced a transient
      membrane potential hyperpolarization with a marked reduction in the amplitude of
      membrane potential oscillations. Locally applied strychnine did not change the
      duration of the sustained depolarizations, suggesting that mechanisms other than
      glycinergic inhibition are involved in ending the sustained depolarizations in RS
      cells. It is concluded that excitatory glutamatergic inputs, including ascending
      spinal feedback, cooperate with intrinsic properties of RS cells to maintain the
      cells depolarized for prolonged periods, sustaining long bouts of escape
      swimming.

PMID- 19176825
TI  - Opposing aminergic modulation of distinct spinal locomotor circuits and their
      functional coupling during amphibian metamorphosis.
AB  - The biogenic amines serotonin (5-HT) and noradrenaline (NA) are well known
      modulators of central pattern-generating networks responsible for vertebrate
      locomotion. Here we have explored monoaminergic modulation of the spinal circuits
      that generate two distinct modes of locomotion in the metamorphosing frog Xenopus
      laevis. At metamorphic climax when propulsion is achieved by undulatory larval
      tail movements and/or by kicking of the newly developed adult hindlimbs, the
      underlying motor networks remain spontaneously active in vitro, producing either
      separate fast axial and slow appendicular rhythms or a single combined rhythm
      that drives coordinated tail-based and limb-based swimming in vivo. In isolated
      spinal cords already expressing distinct axial and limb rhythms, bath-applied 5
      HT induced coupled network activity through an opposite slowing of axial
      rhythmicity (by increasing motoneuron burst and cycle durations) and an
      acceleration of limb rhythmicity (by decreasing burst and cycle durations). In
      contrast, in preparations spontaneously expressing coordinated fictive
      locomotion, exogenous NA caused a dissociation of spinal activity into separate
      faster axial and slower appendicular rhythms by decreasing and increasing burst
      and cycle durations, respectively. Moreover, in preparations from premetamorphic
      and postmetamorphic animals that express exclusively axial-based or limb-based
      locomotion, 5-HT and NA modified the developmentally independent rhythms in a
      similar manner to the amines' opposing effects on the coexisting circuits at
      metamorphic climax. Thus, by exerting differential modulatory actions on one
      network that are opposite to their influences on a second adjacent circuit, these
      two amines are able to precisely regulate the functional relationship between
      different rhythmogenic networks in a developing vertebrate's spinal cord.

PMID- 19176824
TI  - The COP9 signalosome is required for light-dependent timeless degradation and
      Drosophila clock resetting.
AB  - The ubiquitin-proteasome system plays a major role in the rhythmic accumulation
      and turnover of molecular clock components. In turn, these approximately 24 h
      molecular rhythms drive circadian rhythms of behavior and physiology. In
      Drosophila, the ubiquitin-proteasome system also plays a critical role in light
      dependent degradation of the clock protein Timeless (TIM), a key step in the
      entrainment of the molecular clocks to light-dark cycles. Here, we investigated
      the role of the COP9 signalosome (CSN), a general regulator of protein
      degradation, in fly circadian rhythms. We found that null mutations in the genes
      encoding the CSN4 and CSN5 subunits prevent normal TIM degradation by light in
      the pacemaker lateral neurons (LNs) as does LN-specific expression of a dominant
      negative CSN5 transgene. These defects are accompanied by strong reductions in
      behavioral phase shifts of adult flies lacking normal CSN5 activity in LNs.
      Defects in TIM degradation and resetting of behavioral phases were rescued by
      overexpression of Jetlag (JET), the F-box protein required for light-mediated TIM
      degradation. Flies lacking normal CSN activity in all clock neurons are rhythmic
      in constant light, a phenotype previously associated with jet mutants. Together,
      these data indicate that JET and the CSN lie in a common pathway leading to light
      dependent TIM degradation. Surprisingly, we found that manipulations that
      strongly inhibit CSN activity had minimal effects on circadian rhythms in
      constant darkness, indicating a specific role for the CSN in light-mediated TIM
      degradation.

PMID- 19176826
TI  - Connectivity-based parcellation of human cingulate cortex and its relation to
      functional specialization.
AB  - Whole-brain neuroimaging studies have demonstrated regional variations in
      function within human cingulate cortex. At the same time, regional variations in
      cingulate anatomical connections have been found in animal models. It has,
      however, been difficult to estimate the relationship between connectivity and
      function throughout the whole cingulate cortex within the human brain. In this
      study, magnetic resonance diffusion tractography was used to investigate
      cingulate probabilistic connectivity in the human brain with two approaches.
      First, an algorithm was used to search for regional variations in the
      probabilistic connectivity profiles of all cingulate cortex voxels with the whole
      of the rest of the brain. Nine subregions with distinctive connectivity profiles
      were identified. It was possible to characterize several distinct areas in the
      dorsal cingulate sulcal region. Several distinct regions were also found in
      subgenual and perigenual cortex. Second, the probabilities of connection between
      cingulate cortex and 11 predefined target regions of interest were calculated.
      Cingulate voxels with a high probability of connection with the different targets
      formed separate clusters within cingulate cortex. Distinct connectivity
      fingerprints characterized the likelihood of connections between the
      extracingulate target regions and the nine cingulate subregions. Last, a meta
      analysis of 171 functional studies reporting cingulate activation was performed.
      Seven different cognitive conditions were selected and peak activation
      coordinates were plotted to create maps of functional localization within the
      cingulate cortex. Regional functional specialization was found to be related to
      regional differences in probabilistic anatomical connectivity.

PMID- 19176827
TI  - Contrasting activity profile of two distributed cortical networks as a function
      of attentional demands.
AB  - Recent human functional MRI (fMRI) studies have revealed that two widely
      distributed groups of cortical areas display inverse changes in activity when
      attentional demands increase, with one group showing higher (task-on) and the
      second lower (task-off) blood oxygen level-dependent (BOLD) signals. Moreover,
      task-on and task-off regions also exhibit slow (<0.2 Hz) inversely correlated
      fluctuations in BOLD signal at rest. However, the neuronal correlates of these
      reciprocal BOLD signal fluctuations are unknown. Here, we addressed this question
      using simultaneous recordings of unit activity and local field potentials (LFPs)
      in the cat homologues of task-on and task-off regions. In all states of
      vigilance, LFP power was lower in task-off than task-on regions with no
      difference in firing rates. Both sets of regions displayed slow (0.5-0.15 Hz)
      cyclical modulations in LFP power in all frequency bands but with large and
      variable phase differences such that task-on and task-off regions were often
      anticorrelated. Inversely correlated LFP power fluctuations were state-dependent
      in that they were much more frequent in waking and paradoxical sleep than in slow
      wave sleep. Moreover, consistent with fMRI findings, when attentional demands
      increased, LFP power in task-on and task-off regions changed in opposite
      directions, further augmenting and decreasing, respectively. At odds with
      previous fMRI studies, however, the decreased LFP power in task-off regions was
      associated with increased firing rates, suggesting that the engagement of task
      off regions might not be reduced but in fact enhanced during attention.

PMID- 19176828
TI  - Fgfr1 is required for cortical regeneration and repair after perinatal hypoxia.
AB  - Chronic postnatal hypoxia causes an apparent loss of cortical neurons that is
      reversed during recovery (Fagel et al., 2006). The cellular and molecular
      mechanisms underlying this plasticity are not understood. Here, we show that
      chronic hypoxia from postnatal days 3 (P3) to 10 causes a 30% decrease in
      cortical neurons and a 24% decrease in cortical volume. T-brain-1 (Tbr1)(+) and
      SMI-32(+) excitatory neuron numbers were completely recovered 1 month after the
      insult, but the mice showed a residual deficit in Parvalbumin(+) and
      Calretinin(+) GABAergic interneurons. In contrast, hypoxic mice carrying a
      disrupted fibroblast growth factor receptor-1 (Fgfr1) gene in GFAP+ cells [Fgfr1
      conditional knock-out (cKO)], demonstrated a persistent loss of excitatory
      cortical neurons and a worsening of the interneuron defect. Labeling
      proliferating progenitors at P17 revealed increased generation of cortical
      NeuN(+) and Tbr1(+) excitatory neurons in wild-type mice subjected to hypoxic
      insult, whereas Fgfr1 cKO failed to mount a cortical neurogenetic response.
      Hypoxic wild-type mice also demonstrated a twofold increase in cell proliferation
      in the subventricular zone (SVZ) at P17 and a threefold increase in neurogenesis
      in the olfactory bulb (OB) at P48, compared with normoxic mice. In contrast,
      Fgfr1 cKO mice had decreased SVZ cell proliferation and curtailed reactive
      neurogenesis in the OB. Thus, the activation of FGFR-1 in GFAP+ cells is required
      for neuronal recovery after neonatal hypoxic injury, which is attributable in
      part to enhanced cortical and OB neurogenesis. In contrast, there is incomplete
      recovery of inhibitory neurons after injury, which may account for persistent
      behavioral deficits.

PMID- 19176829
TI  - Deafness and permanently reduced potassium channel gene expression and function
      in hypothyroid Pit1dw mutants.
AB  - The absence of thyroid hormone (TH) during late gestation and early infancy can
      cause irreparable deafness in both humans and rodents. A variety of rodent models
      have been used in an effort to identify the underlying molecular mechanism. Here,
      we characterize a mouse model of secondary hypothyroidism, pituitary
      transcription factor 1 (Pit1(dw)), which has profound, congenital deafness that
      is rescued by oral TH replacement. These mutants have tectorial membrane
      abnormalities, including a prominent Hensen's stripe, elevated beta-tectorin
      composition, and disrupted striated-sheet matrix. They lack distortion product
      otoacoustic emissions and cochlear microphonic responses, and exhibit reduced
      endocochlear potentials, suggesting defects in outer hair cell function and
      potassium recycling. Auditory system and hair cell physiology, histology, and
      anatomy studies reveal novel defects of hormone deficiency related to deafness:
      (1) permanently impaired expression of KCNJ10 in the stria vascularis of Pit1(dw)
      mice, which likely contributes to the reduced endocochlear potential, (2)
      significant outer hair cell loss in the mutants, which may result from cellular
      stress induced by the lower KCNQ4 expression and current levels in Pit1(dw)
      mutant outer hair cells, and (3) sensory and strial cell deterioration, which may
      have implications for thyroid hormone dysregulation in age-related hearing
      impairment. In summary, we suggest that these defects in outer hair cell and
      strial cell function are important contributors to the hearing impairment in
      Pit1(dw) mice.

PMID- 19176831
TI  - Network architecture of gap junction-coupled neuronal linkage in the striatum.
AB  - Previous studies have revealed the existence of gap junctions between GABAergic
      interneurons of a particular type in the striatum. Because of the technical
      difficulties, however, there is no information about their positions within the
      striatal circuitry. We have developed a method to detect neuronal gap junctions
      reliably at the light microscopic level and thereby explored the network
      architecture of the gap junctional linkage. Gap junction-coupled networks among
      parvalbumin-containing GABAergic interneurons extended nonuniformly in the feline
      striatum. They were located predominantly in the methionine-enkephalin-poor
      matrix. Moreover, the density of gap junctional coupling showed a marked regional
      difference along the anterior-posterior axis of the striatum. The densest
      interconnectivity was found in the posterior part of both caudate nucleus and
      putamen that corresponds to the sensory-recipient area of the feline striatum.
      Electron microscopic observations provided clear evidence of internalization of
      neuronal gap junction, indicating the dynamic nature of gap junctional linkage
      between neurons in vivo. The nonuniform organization of gap junction networks
      suggests differential modes of information processing in heterogeneous subregions
      of the striatum.

PMID- 19176830
TI  - Genetically determined interaction between the dopamine transporter and the D2
      receptor on prefronto-striatal activity and volume in humans.
AB  - Dopamine modulation of neuronal activity during memory tasks identifies a
      nonlinear inverted-U shaped function. Both the dopamine transporter (DAT) and
      dopamine D(2) receptors (encoded by DRD(2)) critically regulate dopamine
      signaling in the striatum and in prefrontal cortex during memory. Moreover, in
      vitro studies have demonstrated that DAT and D(2) proteins reciprocally regulate
      each other presynaptically. Therefore, we have evaluated the genetic interaction
      between a DRD(2) polymorphism (rs1076560) causing reduced presynaptic D(2)
      receptor expression and the DAT 3'-VNTR variant (affecting DAT expression) in a
      large sample of healthy subjects undergoing blood oxygenation level-dependent
      (BOLD)-functional magnetic resonance imaging (MRI) during memory tasks and
      structural MRI. Results indicated a significant DRD(2)/DAT interaction in
      prefrontal cortex and striatum BOLD activity during both working memory and
      encoding of recognition memory. The differential effect on BOLD activity of the
      DAT variant was mostly manifest in the context of the DRD(2) allele associated
      with lower presynaptic expression. Similar results were also evident for gray
      matter volume in caudate. These interactions describe a nonlinear relationship
      between compound genotypes and brain activity or gray matter volume.
      Complementary data from striatal protein extracts from wild-type and D(2) knock
      out animals (D2R(-/-)) indicate that DAT and D(2) proteins interact in vivo.
      Together, our results demonstrate that the interaction between genetic variants
      in DRD(2) and DAT critically modulates the nonlinear relationship between
      dopamine and neuronal activity during memory processing.

PMID- 19176832
TI  - Neural correlates of probabilistic category learning in patients with
      schizophrenia.
AB  - Functional neuroimaging studies of probabilistic category learning in healthy
      adults report activation of cortical-striatal circuitry. Based on previous
      findings of normal learning rate concurrent with an overall performance deficit
      in patients with schizophrenia, we hypothesized that relative to healthy adults,
      patients with schizophrenia would display preserved caudate nucleus and abnormal
      prefrontal cortex activation during probabilistic category learning. Forty
      patients with schizophrenia receiving antipsychotic medication and 25 healthy
      participants were assessed on interleaved blocks of probabilistic category
      learning and control tasks while undergoing blood oxygenation level-dependent
      functional magnetic resonance imaging. In addition to the whole sample of
      patients with schizophrenia and healthy adults, a subset of patients and healthy
      adults matched for good learning was also compared. In the whole sample analysis,
      patients with schizophrenia displayed impaired performance in conjunction with
      normal learning rate relative to healthy adults. The matched comparison of
      patients and healthy adults classified as good learners revealed greater caudate
      and dorsolateral prefrontal cortex activity in the healthy adults and greater
      activation in a more rostral region of the dorsolateral prefrontal, cingulate,
      parahippocampal and parietal cortex in patients. These results demonstrate that
      successful probabilistic category learning can occur in the absence of normal
      frontal-striatal function. Based on analyses of the patients and healthy adults
      matched on learning and performance, a minority of patients with schizophrenia
      achieve successful probabilistic category learning and performance levels through
      differential activation of a circumscribed neural network which suggests a
      compensatory mechanism in patients showing successful learning.

PMID- 19176833
TI  - What can we learn from quality improvement research? A critical review of
      research methods.
AB  - This article presents a systematic review of the research methods used to study
      quality improvement (QI) effectiveness in health care organizations. The review
      relied on existing literature as well as emergent themes to identify types of QI
      programs (e.g., data/feedback, information technology, staff education) and
      quality outcomes (e.g., mortality, morbidity, unnecessary variation). Studies
      were separated into four categories according to the type of organization in
      which the QI program was introduced: (a) hospital, (b) nursing home, (c)
      physician group, and (d) other health care organization. Results of the review
      indicate that most QI effectiveness research is conducted in hospital settings,
      is focused on multiple QI interventions, and utilizes process measures as
      outcomes. The review also yielded substantial variation with respect to the study
      designs used to examine QI effectiveness. The article concludes with a critique
      of these designs and suggestions for ways future research could address these
      shortcomings.

PMID- 19176834
TI  - Is maternal asthma a life or death issue for the baby?

PMID- 19176835
TI  - The pulmonary protein C system: preventive or therapeutic target in acute lung
      injury?

PMID- 19176836
TI  - Pleural ultrasound.

PMID- 19176837
TI  - Traffic-related air pollution, genetics and asthma development in children.

PMID- 19176838
TI  - Generalised maculopapular rash and multiple nodular pulmonary lesions in an HIV
      infected man.

PMID- 19176842
TI  - Gastro-oesophageal reflux and aspiration in patients with advanced lung disease.
AB  - Numerous small observational studies have shown that gastro-oesophageal reflux is
      prevalent among patients with advanced lung disease. The fundamental concern is
      that reflux is a risk factor for recurrent microaspiration, which may cause lung
      injury. For example, in lung transplant patients, a molecular marker of
      aspiration was a risk factor for the bronchiolitis obliterans syndrome in one
      study. To date, however, there are no large prospective studies measuring the
      impact of aspiration on clinical outcomes. The major obstacle limiting the study
      of reflux and aspiration in patients with advanced lung disease is the absence of
      a reliable diagnostic tool. Proximal oesophageal acid detection by pH monitoring
      is the only widely available measure of aspiration risk. Impedance monitoring may
      be a superior measure of aspiration risk as it measures both acid and non-acid
      reflux episodes. Molecular markers of aspiration, such as pepsin or bile salts in
      the bronchoalveolar lavage or exhaled breath condensate, may be the optimal
      diagnostic tests, but they are not currently available outside the research
      setting. Larger observational studies are needed to determine the following: (1)
      the clinical significance of aspiration in patients with advanced lung disease
      and in patients who have had lung transplantation and (2) the diagnostic test
      that best predicts adverse outcomes.

PMID- 19176843
TI  - Safety and effectiveness of vascular endoprosthesis for malignant superior vena
      cava syndrome.
AB  - BACKGROUND: Superior vena cava syndrome management has been traditionally
      radiation therapy, chemotherapy or chemoradiation, depending on the underlying
      malignancy involved and individual clinicopathological features of the case.
      Recent emergence of endovascular stents offer the opportunity for immediate
      relief of the venous stenosis. This review examines findings from the published
      series which used endovascular prosthesis for this syndrome with regards to
      efficacy and safety. METHODS: Literature search identified studies using
      endovascular stents as initial therapy or for recurrence of malignant superior
      vena cava syndrome. Effectiveness and toxicity from stent placement was assessed.
      RESULTS: Endovascular stent placement provides immediate haemodynamic relief of
      venous compression either before or after definitive therapy in the majority of
      cancer patients. Severe bleedings, cardiopulmonary complications and stent
      migrations remain significant problems for patient management. CONCLUSIONS:
      Endovascular prosthesis is an effective modality for malignant superior vena cava
      syndrome with acceptable morbidity. Prospective studies should be performed to
      determine the optimal anticoagulation regimen.

PMID- 19176844
TI  - Transient correction of the basic defect in sweat glands in an individual with
      cystic fibrosis carrying the complex CFTR allele F508del-R553Q.
AB  - The molecular pathology of mutant F508del CFTR is partially corrected in vitro by
      the secondary amino acid substitution R553Q in the ABC signature motif. An
      individual with the CFTR genotype R553X/F508del-R553Q showed the typical symptoms
      and electrophysiological anomalies of cystic fibrosis in the airways and
      intestine. Sweat chloride concentrations were normal early in life, but were
      later raised into the range that is diagnostic for cystic fibrosis, suggesting
      that R553Q could temporarily correct the basic defect in sweat glands. R553Q
      caused a delay in diagnosis because of false negative sweat tests but was not a
      disease reverting suppressor mutation as had been inferred from cellular models.

PMID- 19176846
TI  - The role of specialist lung cancer nurses in the UK: a national survey.

PMID- 19176847
TI  - Local guidelines for management of adult community acquired pneumonia: a survey
      of UK hospitals.

PMID- 19176848
TI  - GOLD stage 1 is crying wolf.

PMID- 19176849
TI  - Pulmonary scedosporium infection as a complication of infliximab therapy for
      ankylosing spondylitis.

PMID- 19176851
TI  - Knowledge development and programs of research.

PMID- 19176850
TI  - Steroid interaction with a single potentiating site is sufficient to modulate
      GABA-A receptor function.
AB  - Neuroactive steroids are efficacious potentiators of GABA-A receptors. Recent
      work has identified a site in the alpha1 subunit of the GABA-A receptor, that is
      essential for potentiation by steroids. However, each receptor contains two
      copies of the alpha1 subunit. We generated concatemers of subunits so that the
      alpha1 subunits could be mutated separately and examined the consequences of
      mutations that remove potentiation by most neurosteroids (alpha1 Q241L, alpha1
      Q241W). Concatemers were expressed in Xenopus laevis oocytes, and activation by
      GABA, potentiation by neurosteroids, and the agonist activity of piperidine-4
      sulfonic acid (P4S) were determined. When the alpha1 Q241L mutation is present in
      alpha1 subunits the EC(50) for activation by GABA is shifted to higher
      concentration and potentiation by neurosteroids is diminished. When the alpha1
      Q241W mutation is expressed, the EC(50) for GABA is shifted to lower
      concentration, the relative efficacy of P4S is increased, and potentiation by
      neurosteroids is diminished. Mutation of only one alpha1 subunit does not produce
      the full effect of mutating both sites. Overall, the data demonstrate that at a
      macroscopic level, the presence of a single wild-type steroid-binding site is
      sufficient to mediate responses to steroid, but both must be mutated to
      completely remove the effects of steroids. Differences between the two sites seem
      to be relatively subtle.

PMID- 19176852
TI  - The question of time.

PMID- 19176853
TI  - An exploration of the perception of time from the perspective of the Science of
      Unitary Human Beings.
AB  - What is time? The science of unitary human beings describes pandimensional
      reality as a domain without spatial or temporal attributes. As part of this
      pandimensional reality, unitary human beings experience time as passing, and
      involving the past, present, and future. The theory of accelerating evolution
      describes changes in human and environmental energy fields that are always
      accelerating and are manifested as differences in the experience of time as being
      slow, fast, and still. Time, be it measured or experienced, has no meaning in and
      of itself, but can only be understood in terms of the ever-evolving life process.

PMID- 19176854
TI  - Intentionality, consciousness, and creating community.
AB  - Intentionality is briefly explored from the perspective of seminal written works
      on therapeutic touch and recorded conversations with Martha E. Rogers. This
      overview hints at possible interrelationships among intentionality,
      consciousness, and creating community, along with conceptual ambiguities, which
      are explored in detail by Zahourek and Larkin in this column.

PMID- 19176855
TI  - Consciousness, intentionality, and community: Unitary perspectives and research.
AB  - Consciousness and intentionality often have been related and studied together.
      These concepts also are readily viewed and understood for practice, research, and
      education in a unitary paradigm. How these ideas relate to community is less
      known. Considering the expansion of our capacity for communication through the
      World Wide Web and other technologic advances and appreciating recent research on
      the nonlocal character of intentionality and consciousness, it is more apparent
      how concepts of community can be seen in the same unitary context. The authors
      address these issues and review relevant nursing research.

PMID- 19176856
TI  - Transparency in nursing leadership: a chosen ethic.
AB  - The concept of transparency has been viewed as an essential leadership attribute
      or element in healthcare organizational structures and processes. While viewed as
      something that is desired and valued, there is a lack of nursing disciplinary
      literature that defines the concept and its possible meanings. This column
      provides a beginning definition of transparency from the humanbecoming nursing
      theoretical perspective and launches a discussion with potential ethical
      implications for leadership in nursing practice and education.

PMID- 19176857
TI  - Learning with leaders.
AB  - This column focuses on ideas concerning leaders and leadership. The author
      proposes that leadership is about showing up and participating with others in
      doing something. "Mandela: His 8 Lessons of Leadership" by Richard Stengel is
      explored in light of selected philosophical writings, literature on nursing
      leadership, and nurse theorist Rosemarie Rizzo Parse's humanbecoming leading
      following model. Teaching-learning questions are then posed to stimulate further
      reflection on the lessons of leadership.

PMID- 19176858
TI  - A comparison of two nursing theories in practice: Peplau and Parse.
AB  - This column illuminates nursing practice through two unique theoretical
      perspectives: Peplau's theory of interpersonal relations and Parse's theory of
      humanbecoming. Processes of each practice method will be explicated as each is
      related to a practice scenario. The key differences between Peplau's and Parse's
      practice methodologies are identified. Nursing is a unique, evolving,
      everchanging profession for which theory can be used as a guide for practice.
      This column demonstrates two of these unique theories. Whether through health
      promotion or quality of life from the person's perspective, theory provides
      meaning in nursing practice and in everyday life.

PMID- 19176859
TI  - The impact of Dorothea E. Orem's life and work: an interview with Orem scholars.
AB  - This column serves as a tribute to Dorothea Orem's work and focuses on her
      leadership in the development of nursing science and nursing theory. Nurse
      scholars give a picture of Orem's contributions over her life and reflections
      about the future of nursing and healthcare.

PMID- 19176860
TI  - Nurses' experiences of feeling respected-not respected.
AB  - Feeling respected-not respected is an experience integral with the ways nurses
      choose to describe the quality of their work environments and with the quality of
      care they provide to patients and families. The purposes of this study were to
      enhance understanding of nurses' experiences of feeling respected-not respected,
      and to provide new knowledge about quality of work-life related to feeling
      respected-not respected. The Parse research method was used to answer the
      research question, What is the structure of the lived experience of feeling
      respected-not respected? Participants were 37 nurses in staff and leadership
      roles at a large teaching hospital. The structure, feeling respected-not
      respected is affirming-not affirming attentiveness with diverse affiliations
      arising with assuredness-unassuredness, is discussed in light of the
      humanbecoming theory, related literature, leadership, and future research.

PMID- 19176861
TI  - Adaptation to spinal cord injury for families post-injury.
AB  - Based on the Roy adaptation model, this cross-sectional study was conducted with
      15 spinal cord injured individuals and their family members to examine the
      physical, emotional, functional, and social components of adaptation to spinal
      cord injury at 1 year (n=7 dyads) and 3 years (n=8 dyads) post-injury. Findings
      indicate that spinal cord injured individuals and their family members,
      regardless of time since the initial injury, have a moderate level of adaptation
      and adjustment to spinal cord injury. The data suggested that adaptation to
      spinal cord injury during the first 3 years can be enhanced by providing ongoing
      social and educational support for not only the injured individuals, but also
      their family members.

PMID- 19176862
TI  - Nursing care for adaptation.
AB  - The Roy adaptation model has been adopted as the frame of reference for the
      nursing curriculum at the Universidad de La Sabana School of Nursing in Colombia.
      The purpose of this paper is to discuss, through an example, the application
      process of the Roy model, the reflection that has been developed to study in
      great depth its central concepts and scientific and philosophic principles, and
      to explain the concept of nursing care for adaptation as a fundamental aspect for
      its application. Likewise, the process generated from the model's application in
      teaching and practice are presented.

PMID- 19176863
TI  - Living with changing expectations for women with high-risk pregnancies: a Parse
      method study.
AB  - The purpose of this research was to uncover the structure of the lived experience
      of living with changing expectations from the perspectives of women with high
      risk pregnancies. The researchers' nursing theoretical perspective is the
      humanbecoming theory and the Parse research method was used. For the
      participants, living with changing expectations is foreboding disquietude arising
      with arduous restrictions, while envisioning the yearned-for with mitigating
      nurturing engagements. Findings enhance the theory of humanbecoming as well as
      enhance understanding of the experience of living with changing expectations.
      Recommendations for future research and practice are discussed.

PMID- 19176864
TI  - Beyond cultural competence: nursing practice with political refugees.

PMID- 19176865
TI  - A phenomenological study on the experience of North Korean refugees.
AB  - The purpose of this phenomenological study was to explore the experience of North
      Korean refugees living in South Korea. From the analysis of the participants'
      comments, six essences were identified: entrance to a new world after struggling
      for survival, unexpected shock and chaos, reconsidering the reasons for leaving
      North Korea, recovery from trauma, rebuilding meaning, and posttraumatic growth.

PMID- 19176866
TI  - Lower frequency of daily teeth brushing is related to high prevalence of
      cardiovascular risk factors.
AB  - This study sought to investigate relationships between frequency of daily teeth
      brushing and prevalences of diabetes mellitus, hypertension and dyslipidemia.
      Subjects were 54,551 residents of Chiba City, Japan (20,155 men and 34,396 women)
      who underwent routine health examinations in 2004. Diabetes mellitus was defined
      as a fasting plasma glucose level > or =126 mg/dl or a non-fasting plasma glucose
      level > or =200 mg/dl and/or receiving treatment for diabetes. Hypertension was
      defined as systolic blood pressure (SBP) > or =140 mmHg, diastolic blood pressure
      (DBP) > or =90 mmHg and/or receiving treatment for hypertension. Dyslipidemia was
      defined according to the two criteria: high triglyceride and/or low high density
      lipoprotein cholesterol (TG > or = 150 mg and/or HDL-C < 40 mg/dl), and high
      total cholesterol (TC > or = 220 mg/dl). According to Pearson's chi-square tests
      and logistic regression analysis adjusted for age, BMI, smoking habit, alcohol
      consumption and daily walking time, lower frequency of teeth brushing is related
      to higher prevalences of diabetes mellitus, hypertension and high TG and/or low
      HDL-C, in both men and women. Total cholesterol status, however, showed no
      significant relationship. Maintaining good oral hygiene by regular teeth brushing
      may prevent type 2 diabetes, hypertension and dyslipidemia.

PMID- 19176867
TI  - Association of various dimensions of hot flashes with systemic levels of gonadal
      steroids.
AB  - Hot flashes, the cardinal sign of menopausal vasomotor symptoms, are experienced
      by millions of women. The experience of hot flashes is characterized by
      significant inter- and intra-individual variability among women. The goals of
      this study were to compare concentrations of gonadal hormones between menopausal
      women with hot flashes (HF) and those with no HF, and to characterize the
      association between steroid levels and multiple dimensions of hot flashes.
      Menopausal women, with HF and with no HF, participated in four study sessions,
      one every 2 months. The Menopausal Vasomotor Symptom (MVS) survey was used to
      collect subjective data on various dimensions of hot flashes. Concentrations of
      gonadal hormones were measure at each bi-monthly session. Steroid levels were
      correlated to duration, frequency, length of each episode, timing, intensity, and
      bothersomeness of hot flashes. Data from twenty (n = 20) women with HF and
      fifteen (n = 15) with no HF with similar demographic profiles were analyzed. The
      results from the present study showed that systemic levels of estrone and
      progesterone were significantly lower in women experiencing HF than in
      asymptomatic women. There was a significant association between levels of
      estradiol, estrone, progesterone, and androstenedione, but not testosterone, with
      duration, frequency, timing, intensity, and bothersomeness of HF. The findings
      from this preliminary study suggest that management of symptoms associated with
      vasomotor HF should be individualized and guided by two factors: (i) thorough
      assessment of subjectively reported multiple dimensions of hot flashes, and (ii)
      levels of circulating gonadal steroids representing an average from 2-4 measures.
      This approach may lead to more targeted, effective, and safe management of
      vasomotor symptoms in the rapidly growing population of menopausal women.

PMID- 19176868
TI  - Gastrointestinal microflora and mucins may play a critical role in the
      development of 5-Fluorouracil-induced gastrointestinal mucositis.
AB  - 5-Fluorouracil (5-FU) is a commonly used chemotherapy agent in clinical oncology
      practice. Two of its major side effects are mucositis and diarrhoea. The
      structure of mucins offers mucosal protection, and allows maintenance of
      intestinal flora by providing attachment sites and preventing bacterial
      overgrowth and/or penetration. The aim of this study was to investigate changes
      in mucin secretion and microflora following treatment with 5-FU. Female DA rats
      were given a single 150 mg/ kg i.p. dose of 5-FU. Rats were killed at various
      time points after treatment. Control rats received no treatment. Jejunum, colon
      and faecal samples were collected. Standard microbiological culture techniques
      were used to identify bacteria, and real-time PCR was used to quantify bacteria
      in faecal samples. Goblet cells and cavitated goblet cells (having undergone
      mucus exocytosis) were also counted. Statistical analysis was carried out using
      Kruskal-Wallis test, a non-parametric method of testing equality of group
      medians. Following treatment with 5-FU, we showed decreases in Clostridium spp.,
      Lactobacillus spp. and Streptococcus spp., and an increase in Escherichia spp. in
      the jejunum. In the colon, 5-FU caused decreases in Enterococcus spp.,
      Lactobacillus spp. and Streptococcus spp. Real-time PCR of faecal samples showed
      decreasing trends in Lactobacillus spp. and Bacteroides spp., and an increasing
      trend in E. coli. Significant increases (P < 0.05) were seen in Clostridium spp.
      and Staphylococcus spp. at 24 h. Goblet cell numbers decreased significantly in
      the jejunum from 24-72 h, with a significant increase in the percentage of
      cavitated goblet cells. In conclusion, 5-FU treatment causes significant changes
      in intestinal flora and mucin secretion in rats. These changes could result in
      systemic effects and, in particular, may contribute to the development of
      chemotherapy-induced mucositis.

PMID- 19176869
TI  - Grafts of porcine small intestinal submucosa with cultured autologous oral
      mucosal epithelial cells for esophageal repair in a canine model.
AB  - The acellular porcine small intestinal submucosa (SIS) has been successfully used
      for esophagoplasty. However, it does not lead to a complete epithelialization in
      a canine model. A cellular component may be required for better reconstruction.
      The present study was undertaken to investigate the feasibility and effectiveness
      of the combination of SIS and autologous oral mucosal epithelial cells (OMECs)
      for esophageal reconstruction. The OMECs harvested from beagle dogs were cultured
      and propagated, and the 3rd passage cells were seeded on a single-layer SIS. Male
      beagle dogs were subjected to surgical resection to produce cervical esophageal
      defects (5 cm in length, 180 degrees in range). SIS with or without OMECs was
      patched on the esophageal defects. Barium esophagram, immunohistochemistry, and
      histology were performed to evaluate the therapeutic effectiveness. Four weeks
      after surgery, the histological examination showed a complete re
      epithelialization and almost no inflammation in the SIS with OMECs group. But in
      the SIS group, only a partial epithelialization was observed along with
      inflammation. Eight weeks after surgery, the squamous epithelium was found to
      cover the entire graft surface in both groups; however, the muscular regeneration
      was observed in the SIS with OMECs, but not in the SIS group. The graft of SIS
      combined with autologous OMECs promotes re-epithelialization and muscular
      regeneration. It is an effective alternative method for esophageal repair.

PMID- 19176870
TI  - Phosphorylated insulin like growth factor-I receptor expression and its clinico
      pathological significance in histologic subtypes of human thyroid cancer.
AB  - Overexpression of insulin-like growth factor-I receptor (IGF-IR) is seen in a
      multitude of human thyroid cancers and correlates with poor prognosis. However,
      recent studies suggest that low phospho-IGF-IR (pIGF-IR) expression rather than
      its overexpression may be an indicator of poorly differentiated disease. No
      previous study has evaluated the expression of pIGF-IR to determine if activation
      or loss of expression of this receptor is associated with thyroid tumor
      progression. Accordingly, a quantitative immunohistochemical (IHC) method was
      used to evaluate the clinico-pathological significance of pIGF-IR expression in
      archival samples of human thyroid carcinomas. Quantitative analysis of pIGF-IR
      levels revealed a significant difference in the median index of pIGF-IR between
      different histological subtypes of thyroid cancer (P < 0.001). Specifically, the
      median pIGF-IR index of differentiated thyroid cancers was significantly higher
      than the median index of other poorly differentiated thyroid cancer (P < 0.001).
      This was further confirmed in individual tumor sections of thyroid carcinoma
      where anaplastic and differentiated components co-existed. No significant
      difference was noted in the pIGF-IR index of tumors grouped by size or stage but
      a trend towards lower mean pIGF-IR index was noted in older patients. Our data
      indicates that pIGF-IR is upregulated in a majority of follicular thyroid
      carcinomas, suggesting it may be a potential target for therapy for patients with
      this disease. In addition, since low pIGF-IR expression was found to correlate
      with aggressive human thyroid carcinoma, it also suggests that IGF-IR may not be
      needed for progression of anaplastic thyroid carcinoma possibly because other
      cell signaling pathways are activated, obviating the need for IGF-IR signaling.
      However, more mechanistic studies would be necessary to substantiate the
      possibility that pIGF-IR may be important for differentiation of thyroid tissues
      and is lost with disease progression.

PMID- 19176871
TI  - Mucosal immunization with polyamine transport protein D (PotD) protects mice
      against nasopharyngeal colonization with Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is an encapsulated pathogen that can cause invasive
      disease following colonization of the nasopharynx. Targeting colonization of
      mucosal surfaces may, therefore, be the best approach for vaccination to prevent
      pneumococcal invasive disease. Previous studies in our laboratory have shown that
      immunization with recombinant polyamine transport protein D (PotD) protects mice
      against systemic pneumococcal infections. In this study we investigated the
      efficacy of mucosal immunization with rPotD to protect against pneumococcal
      carriage and invasion in a murine model. Mice were intranasally immunized with
      either rPotD and cholera toxin B subunit (CTB) or CTB alone. Significantly less
      pneumococci were recovered from the nasopharynx of immunized mice compared to the
      control animals following intranasal challenge with either EF3030 (serotype 19F)
      (P < 0.05) or an invasive serotype 4 isolate (TIGR4) (P < 0.05). PotD immunized
      mice also had lesser bacteria in their sinus tissues (P < 0.05), brains (P <
      0.05), lungs and olfactory bulbs following intranasal challenge with TIGR4. ELISA
      analysis demonstrated the presence of IgG antibodies to PotD in the serum and IgA
      antibodies in the saliva. These results indicate that mucosal immunization with
      PotD generates both mucosal and systemic immune responses and prevents
      establishment of nasopharyngeal carriage by multiple pneumococcal serotypes.
      Thus, PotD is a potentially important antigen for development of a pneumococcal
      protein vaccine.

PMID- 19176872
TI  - Activity markers of the anti-breast carcinoma cell growth fractions of Vernonia
      amygdalina extracts.
AB  - Vernonia amygdalina (VA) is an edible plant of the Asteraceae family used in many
      herbal formulations prescribed by herbalists for many diseases. We have
      previously reported that aqueous VA extracts inhibit the growth of estrogen
      receptor-positive human breast cancerous cells in vitro. Activity markers of the
      VA extracts have not been previously identified or characterized. Hence, the
      objective of this study was to identify activity markers of the VA extracts
      associated with cell growth inhibition. Extraction of VA with multiple solvents
      of various polarity indexes yielded three fractions (A-1-2, B-1-3) that
      significantly inhibited cell growth (P < 0.05) at 0.1 mg/ml concentration. At a
      higher concentration of 1 mg/ml, six fractions of hexane, chloroform, butanol,
      and ethyl acetate (A-1-3, B-1-4) inhibited DNA synthesis by 76%, 98%, 94%, 98%,
      98%, and 96%, respectively. These fractions were UV-detected from 250-730 nm; and
      all showed three distinct peaks around 410, 431, and 664 nm. Furthermore, HPLC
      analysis of the fractions revealed similar retention times of 2.213, 2.167, and
      2.151 min, respectively. Bioactivity assays showed that HPLC retention of
      approximately 2 min is required for cell growth-inhibitory activity of VA
      fractions. Interestingly, all active fractions exhibited HPLC peaks at
      approximately 2 min. Therefore, the UV and HPLC peaks may be used as predictive
      tools to determine VA extracts activities.

PMID- 19176873
TI  - Acute lung injury:apoptosis and signaling mechanisms.
AB  - Acute lung injury (ALI) has been documented clinically following several
      pathological states such as trauma, septic shock and pneumonia. The
      histopathological characteristics, paired with the production of a number of
      cellular pro-inflammatory mediators, play a crucial role in the progression of
      ALI. During ALI, polymorphonuclear neutrophil (PMN)-mediated apoptosis is delayed
      by macrophages, possibly via effects on the Fas/FasL mediated pathway, leading to
      the accumulation of these cells at the site of injury and inflammation. The
      transcriptional regulation of NFkappaB, CREB, and AP-1 also regulates the
      pathogenesis of ALI. During sepsis and septic shock, we found evidence of
      infiltrating leukocytes in the alveolar spaces along with an increased number of
      TUNEL-positive cells in the lung sections. We also observed an increased
      expression of TRADD and Bax/Bcl(2) ratio at 7 days post-sepsis. In contrast, the
      NFkappaB/IkappaB ratio increased at 1 day post-sepsis. Together, these data
      provide evidence illustrating the induction of apoptosis in lung tissues
      subsequent to the onset of polymicrobial sepsis. The results support the concept
      that the upregulation of apoptosis following lung inflammation plays a crucial
      role in the development of acute lung injury and related disorders such as ARDS.

PMID- 19176874
TI  - In vivo expansion of the mammary stem/ progenitor cell population by xanthosine
      infusion.
AB  - Mammary stem cells provide for growth and maintenance of the mammary gland and
      are therefore of considerable interest as determinants of productivity and
      efficiency of dairy animals and as targets of carcinogenesis in humans.
      Xanthosine treatment was previously shown to promote expansion of hepatic stem
      cells in vitro. The objective of this study was to determine if in vivo treatment
      with xanthosine can increase the mammary stem cell population. Xanthosine was
      infused into the right mammary glands of four female Holstein calves for 5
      consecutive days. Immediately after each xanthosine treatment, calves were
      injected intravenously with 5-bromo-2-deoxyuridine (BrdU). Forty days after the
      final treatment, calves were euthanized and mammary tissue harvested. BrdU-label
      retaining epithelial cells (LREC) were detected immunohistochemically and
      quantified. Retention of BrdU was used as a marker for putative bovine mammary
      stem cells. Infusion of xanthosine into the bovine mammary gland significantly
      increased the number of LREC in treated glands compared to contralateral control
      glands (P < 0.05). LREC averaged 0.4% of epithelial cells in control glands and
      0.8% in xanthosine-treated glands. The increase in LREC in xanthosine-treated
      glands was supported by a concomitant increase in telomerase activity (P < 0.01)
      and a correlation between LREC and telomerase (P < 0.05; r (2) = 0.7). Data
      indicate that in vivo treatment with xanthosine can be used to increase the
      number of mammary stem cells. This is the first demonstration of an in vivo
      treatment to increase the endogenous population of mammary stem cells, with
      utility for biomedical research and dairy management.

PMID- 19176875
TI  - Cruciferous dithiolethione-mediated coordinated induction of total cellular and
      mitochondrial antioxidants and phase 2 enzymes in human primary cardiomyocytes:
      cytoprotection against oxidative/electrophilic stress and doxorubicin toxicity.
AB  - 3H-1,2-dithiole-3-thione (D3T), a cruciferous organosulfur compound, induces
      cytoprotective enzymes in animal cardiovascular cells. However, it remains
      unknown if D3T also upregulates antioxidants and phase 2 enzymes in human
      cardiomyocytes, and protects against cell injury induced by
      oxidative/electrophilic species as well as doxorubicin. In this study, we found
      that D3T (10-50 muM) potently induced a series of antioxidants and phase 2
      enzymes in primary cultured human cardiomyocytes, including superoxide dismutase
      (SOD), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase
      (GPx) glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase 1 (NQO1),
      aldose reductase (AR), and heme oxygenase (HO). D3T treatment also caused
      elevation of SOD, GSH, GR, GPx and GST in the isolated mitochondria. We also
      observed a time-dependent induction by D3T of mRNA expression for Cu,ZnSOD,
      MnSOD, gamma-glutamylcysteine ligase, GR, GSTA1, GSTM1, NQO1, AR, and HO-1.
      Pretreatment with D3T conferred concentration-dependent protection against cell
      injury induced by xanthine oxidase (XO)/xanthine, H(2)O(2), 3
      morpholinosydnonimine, 4-hydroxy-2-nonenal, and doxorubicin. Pretreatment with
      D3T also reduced the formation of intracellular reactive oxygen species by
      XO/xanthine, H(2)O(2), and doxorubicin. In conclusion, this study demonstrated
      that D3T potently upregulated many antioxidants and phase 2 enzymes in human
      cardiomyocytes, which was accompanied by increased resistance to
      oxidative/electrophilic stress and doxorubicin toxicity.

PMID- 19176876
TI  - Mapping excellence in national research systems: the case of Italy.
AB  - The study of "scientific excellence" is taking on increasing importance in the
      development of research policies in many nations. However, scientific excellence
      is difficult to define because of its multidimensional and highly complex
      character. This work contributes to the state of the art by exploring an
      effective, simple, and inexpensive bibliometric methodology that further
      identifies "excellent" centers of research by beginning with the individual
      researchers affiliated with such centers. The study concentrates on public
      research organizations in Italy, analyzing 109 scientific categories of research
      in the "hard" sciences and 157 centers of excellence operating in 60 of these
      categories. Findings from this first application of the methodology should be
      considered exploratory and indicative. With a longer period of observation and
      the addition of further measurements, this methodology could be extended and
      adapted to a variety of national and supranational contexts, aiding policy
      decisions at various levels.

PMID- 19176877
TI  - How do disclosure policies fail? Let us count the ways.
AB  - The disclosure policies of scientific journals now require that investigators
      provide information about financial interests relevant to their research. The
      main goals of these policies are to prevent bias from occurring, to help identify
      bias when it occurs, and to avoid the appearance of bias. We argue here that such
      policies do little to help achieve these goals, and we suggest more effective
      alternatives.

PMID- 19176878
TI  - Select nutrients in the ovine uterine lumen. IV. Expression of neutral and acidic
      amino acid transporters in ovine uteri and peri-implantation conceptuses.
AB  - The availability of specific neutral and acidic amino acids in the uterine lumen
      of ewes increased significantly during the peri-implantation period, but
      mechanisms for their transport into the uterine lumen and uptake by conceptuses
      are not established in any species. In this study, effects of pregnancy,
      progesterone (P4), and interferon tau (IFNT) on expression of neutral and acidic
      amino acid transporters in uteri of cyclic and pregnant ewes and conceptuses were
      studied. SLC1A2, SLC1A3, SLC3A1, SLC6A14, SLC6A19, SLC7A6, SLC38A3, and SLC38A6
      mRNAs were only weakly expressed in the ovine endometrium. However, SLC1A4,
      SLC1A5, SLC7A8, and SLC43A2 mRNAs were detectable in uterine luminal epithelia
      (LE), superficial glandular epithelia (sGE), and/or glandular epithelia (GE).
      SLC1A1 and SLC7A5 mRNAs were most abundant in LE/sGE and GE. SLC1A3 and SLC38A4
      mRNAs were most abundant in uterine stroma. SLC38A6 mRNA was detected only in
      cells with a stromal distribution suggesting immune lineage. SLC1A5 mRNA was
      expressed primarily in LE/sGE and stromal cells, and it was more abundant in
      uteri of pregnant ewes (day x status interaction; P < 0.05). Furthermore, P4
      induced and IFNT further stimulated SLC1A5 expression in LE/sGE. Endometrial
      SLC1A1, SLC7A5, and SLC43A2 mRNAs demonstrated both temporal and cellSLC-specific
      changes. Several mRNAs were detectable in trophectoderm (SLC6A19, SLC7A5, SLC7A6,
      and SLC43A2), while others were more abundant in endoderm (SLC1A4, SLC1A5,
      SLC6A19, SLC7A5, SLC7A6, SLC7A8, and SLC43A2) of conceptuses. These results
      document coordinate changes in expression of transporters that are likely
      responsible for increases in amounts of neutral and acidic amino acids in the
      uterine lumen to support conceptus growth, development, and survival.

PMID- 19176879
TI  - The multi-copy mouse gene Sycp3-like Y-linked (Sly) encodes an abundant spermatid
      protein that interacts with a histone acetyltransferase and an acrosomal protein.
AB  - Deletion analysis has established that genes on the Y chromosome are essential
      for normal sperm production in humans, mice, and Drosophila. In mice, long-arm
      deletions have an impact on spermiogenesis, with the most extensive deletions
      resulting in severe sperm head malformations and infertility. Intriguingly,
      smaller deletions are compatible with fertility but result in a distorted sex
      ratio in favor of females, and recently it was found that Y long-arm deletions
      are also associated with a marked upregulation of several X-encoded and Y-encoded
      spermatid-expressed genes. The mouse Y long arm encodes a number of distinct
      transcripts, each of which derives from multiple gene copies. Of these multicopy
      genes, the recently described Sly has been favored as the gene underlying the
      spermiogenic defects associated with Y long-arm deletions. To assess the
      candidacy of Sly, the expression of this gene was examined in the testis at the
      transcript and protein levels. Sly is transcribed after the first meiotic
      division in secondary spermatocytes and round spermatids and encodes two
      transcript variants, Sly_v1 and Sly_v2 (proteins referred to as SLY1 and SLY2).
      We raised an antibody against SLY1 which detected the protein in round and early
      elongating spermatids, where it is predominantly cytoplasmic. Yeast two-hybrid
      and coimmunoprecipitation studies demonstrated that SLY1 interacts with the
      acrosomal protein DKKL1, the histone acetyltransferase KAT5 (also known as
      TIP60), and the microtubule-associated protein APPBP2. Together, these data
      suggest SLY1 may be involved in multiple processes during spermiogenesis,
      including the control of gene expression and the development or function of the
      acrosome.

PMID- 19176880
TI  - Rapid induction of cell proliferation in the adult female ungulate brain (Ovis
      aries) associated with activation of the reproductive axis by exposure to
      unfamiliar males.
AB  - In many species, the reproductive centers of the brain are profoundly affected by
      sociosexual stimuli. This is particularly evident in female ungulates such as
      sheep, in which exposure to males switches them from reproductively quiescent to
      fertile. In two experiments with female sheep, we tested whether the brain
      centers that control gonadotropin-releasing hormone (GnRH) neuronal activity
      respond differentially to "novel" vs. familiar males and whether the
      neuroendocrine response is associated with increased cell proliferation in the
      hippocampus, a site associated with memory formation. In experiment 1, groups of
      10 female sheep that had previously been habituated to males for 3 mo were re
      exposed to familiar males or were exposed to novel males. Only the novel males
      increased luteinizing hormone (LH) pulse frequency, indicating stimulation of
      GnRH neuronal activity. In experiment 2, groups of six female sheep were injected
      with bromodeoxyuridine (BrdU) and then maintained in isolation from males or
      exposed to novel males. Two days later, the hippocampus and hypothalamus were
      removed and processed for fluorescence immunohistochemistry. Again, exposure to
      males increased LH pulse frequency. Most important, male exposure also doubled
      the number of BrdU-positive cells in the dentate gyrus of the hippocampus. No
      BrdU-positive cells were detected in the hypothalamus. We conclude that the
      stimulus from novel males switches on the reproductive centers of the brain of
      female sheep and rapidly doubles the rate of cell proliferation in the
      hippocampus. The rapidity of this response contrasts with rodents, in which
      several days of exposure to male pheromones seem necessary for an effect on
      neurogenesis.

PMID- 19176881
TI  - Estradiol suppresses glutamatergic transmission to gonadotropin-releasing hormone
      neurons in a model of negative feedback in mice.
AB  - A surge of gonadotropin-releasing hormone (GnRH) release from the brain triggers
      the luteinizing hormone (LH) surge that causes ovulation. The GnRH surge is
      initiated by a switch in estradiol action from negative to positive feedback.
      Estradiol signals critical for the surge are likely transmitted to GnRH neurons
      at least in part via estradiol-sensitive afferents. Using an ovariectomized
      estradiol-treated (OVX+E) mouse model that exhibits daily LH surges, we examined
      changes in glutamate transmission to GnRH neurons during negative feedback and
      positive feedback. Spontaneous glutamatergic excitatory postsynaptic currents
      (EPSCs) mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid/kainate receptors (AMPA/KA Rs) or N-methyl-D-aspartate receptors (NMDARs)
      were recorded in GnRH neurons from OVX+E and OVX mice. There were no diurnal
      changes in the percentage of GnRH neurons from OVX mice exhibiting EPSCs. In
      cells from OVX+E mice, the profile of AMPA/KA R-mediated and NMDAR-mediated EPSCs
      showed changes dependent on time of day. Comparison of AMPA/KA R-mediated EPSC
      frequency in OVX+E and OVX cells showed that estradiol suppressed transmission
      during negative feedback but had no effect during positive feedback. Tetrodotoxin
      treatment to block action potential firing did not affect AMPA/KA R-mediated EPSC
      frequency in OVX cells during negative feedback or in OVX+E cells during positive
      feedback, suggesting that estradiol-induced suppression of glutamate transmission
      may be primarily due to activity-independent changes. The diurnal removal of
      estradiol-induced suppression of AMPA/KA R-mediated glutamate transmission to
      GnRH neurons during positive feedback suggests that the primary role for
      estradiol-induced changes in glutamate transmission may be in mediating negative
      feedback.

PMID- 19176882
TI  - Regulation of baboon fetal pituitary prolactin expression by estrogen.
AB  - We previously showed that fetal adrenal fetal zone growth was increased and the
      number of follicles in the fetal ovary reduced in baboons in which estradiol was
      suppressed by treatment with the aromatase inhibitor letrozole between mid and
      late gestation periods. Because adrenal/ovarian development was restored in
      animals treated with letrozole and estradiol, and both tissues express estrogen
      receptor, we proposed that estrogen regulates fetal adrenal/ovary development via
      a direct action. However, because prolactin can modulate fetal adrenal and adult
      pituitary/ovarian function, the current study determined whether estrogen action
      involved estradiol-regulated changes in fetal prolactin/luteinizing hormone (LH)
      expression. Fetal prolactin levels and the number of prolactin-positive fetal
      pituitary cells (per 0.37 mm(2)) were increased (P < 0.01) between mid (6 +/- 1
      ng/ml; 15.8 +/- 2.4) and late (257 +/- 28 ng/ml; 57.3 +/- 5.1) gestation, reduced
      (P < 0.01) in late-gestation fetuses in which estradiol was suppressed (>95%) by
      letrozole (61 +/- 11 ng/ml; 19.3 +/- 2.0), and minimally but not significantly
      increased by letrozole and estradiol (99 +/- 11 ng/ml; 32.7 +/- 5.2). In
      contrast, the number of LH-positive fetal pituitary cells decreased (P < 0.01)
      between mid (48.8 +/- 9.5) and late (17.4 +/- 3.2) gestation, remained elevated
      (P < 0.01) in estrogen-suppressed animals (56.6 +/- 5.1), and was partially but
      not significantly decreased by letrozole-estradiol (28.8 +/- 5.2). We conclude
      that estrogen regulates fetal pituitary prolactin and LH expression and fetal
      prolactin levels. However, because prolactin and LH expressions in estrogen
      suppressed fetuses were inversely related to previously demonstrated changes in
      adrenal/ovarian development, we propose that estrogen regulates the fetal ovary
      and adrenal gland directly and not via action on the fetal pituitary gland.

PMID- 19176884
TI  - A dominant loss-of-function GJA1 (Cx43) mutant impairs parturition in the mouse.
AB  - Expression of GJA1 (commonly known as connexin43 or Cx43), a major myometrial gap
      junction protein, is upregulated before the onset of delivery, suggesting an
      essential role for Cx43-mediated gap junctional intercellular communication
      (GJIC) in normal uterine contraction during parturition. To determine how a
      disease-linked Cx43 mutation affects myometrial function, we studied a mutant
      mouse model carrying an autosomal dominant mutation (Gja1(Jrt)) in the gene
      encoding Cx43 that displays features of the human genetic disease
      oculodentodigital dysplasia. We found that Cx43 level, specifically the
      phosphorylated species of the protein, is significantly reduced in the myometrium
      of the mutant mice (Gja1(Jrt)/+), as revealed by Western blotting and
      immunostaining. Patch-clamp electrophysiological measurements demonstrated that
      coupling between myometrial smooth muscle cells is reduced to <15% of wild-type,
      indicating that the mutant protein acts dominantly on its wild-type counterpart.
      The phosphorylated species of Cx43 in the mutant myometrium failed to increase
      prior to parturition as well as in response to exogenous estrogen.
      Correspondingly, in vitro experiments with uterine strips revealed weaker
      contraction of the mutant myometrium and reduced responsiveness to oxytocin,
      providing an explanation for the prolonged gestation and presence of suffocated
      fetuses in the uteri that were observed in some of the mutant mice. We conclude
      that the Gja1(Jrt) mutation has a dominant-negative effect on Cx43 function in
      the myometrium, severely reducing GJIC, leading to impaired parturition.

PMID- 19176885
TI  - The role of venous capacitance, circulating catecholamines, and heart rate in the
      hemodynamic response to increased temperature and hypoxia in the dogfish.
AB  - Hypoxia and increased temperature alter venous blood pressures in teleosts
      through active changes in venous tone. Elasmobranchs possess a capacious venous
      system but have limited adrenergic vascular innervation and subambient central
      venous pressure (P(cv)). In this study, we explored venous hemodynamic responses
      to acute temperature increase and moderate (6.9 kPa) and severe (2.5 kPa) hypoxia
      in the dogfish (Squalus acanthias). Normoxic dogfish at 10 degrees C had a P(cv)
      between -0.08 and -0.04 kPa and a mean circulatory filling pressure (P(mcf)) of
      approximately 0.12 kPa. At 16 degrees C, heart rate (f(H)), cardiac output (Q),
      and P(mcf) increased but P(cv) and plasma epinephrine and norepinephrine levels
      were unchanged. In contrast, moderate and severe hypoxia increased P(cv) and
      decreased Q and stroke volume (V(S)). f(H) decreased in severe hypoxia, whereas
      P(mcf) was unaffected despite elevated catecholamine levels. Atropine abolished
      hypoxic reductions in Q, V(S), and f(H), but P(cv) still increased. In contrast
      to the response in teleosts, this study on dogfish suggests that venous
      capacitance changes associated with warming and hypoxia are minimal and likely
      not mediated by circulating catecholamines. Thus hemodynamic status of the
      capacious elasmobranch venous circulation is potentially regulated by blood
      volume shifts from passive flow-mediated events and possibly through myogenic
      mechanisms.

PMID- 19176883
TI  - Conditional deletion of beta-catenin mediated by Amhr2cre in mice causes female
      infertility.
AB  - Follicle-stimulating hormone (FSH) regulation of aromatase gene expression in
      vitro requires the transcriptional coactivator beta-catenin. To ascertain the
      physiological significance of beta-catenin in granulosa cells during
      folliculogenesis, mice homozygous for floxed alleles of beta-catenin were
      intercrossed with Amhr2cre mice. Conditional deletion of beta-catenin in 8-wk-old
      females occurred in derivatives of the Mullerian duct, granulosa cells and,
      surprisingly, in brain, pituitary, heart, liver, and tail. Female mice deficient
      for beta-catenin were infertile, despite reaching puberty and ovulating at the
      expected age, indications of apparently normal ovarian function. In contrast,
      their oviducts were grossly distended, with fewer but healthy oocytes. In
      addition, their uteri lacked implantation sites. Together, these two phenotypes
      could explain the complete loss of fertility. Nevertheless, although the ovary
      appeared normal, with serum estradiol concentrations in the normal range, there
      was marked animal-to-animal variation of mRNAs encoding beta-catenin and
      aromatase. Similarly, inhibin-alpha and luteinizing hormone receptor mRNAs varied
      considerably in whole ovaries, whereas pituitary Fshb mRNA was significantly
      reduced. Collectively, these features suggested cyclization recombination (CRE)
      mediated recombination of beta-catenin may be unstable in proliferating granulosa
      cells, and therefore may mask the suspected steroidogenic requirement for beta
      catenin. We tested this possibility by transducing primary cultures of granulosa
      cells from mice homozygous for floxed alleles of beta-catenin with a CRE
      expressing adenovirus. Reduction of beta-catenin significantly compromised FSH
      stimulation of aromatase mRNA and subsequent production of estradiol.
      Collectively, these data suggest that FSH regulation of steroidogenesis requires
      beta-catenin, a role that remains hidden when tested through Amhr2cre-mediated
      recombination in vivo.

PMID- 19176886
TI  - Responses of the trout cardiac natriuretic peptide system to manipulation of salt
      and water balance.
AB  - Natriuretic peptides (NPs) are evolutionarily conserved hormones that affect
      blood pressure and fluid volume through membrane-bound guanylate cyclase (GC)
      linked natriuretic peptide receptors-A and -B (NPR-A and NPR-B, respectively) in
      a variety of vascular, renal, and other tissues. The principal physiological
      stimulus for cardiac NPs in fish is somewhat debated between two prominent
      theories: regulation of salt balance (osmoregulatory hypothesis) or prevention of
      volume expansion (cardioprotective hypothesis). In the present study, we examined
      atrial and ventricular expression of trout NPs, atrial (ANP), brain (BNP), and
      ventricular (VNP) using Northern (mRNA), Western (NP pro-hormone), and qPCR (GC
      NPR-A and -B mRNA) blot analysis following independent manipulation of plasma
      salt and volume levels after chronic exposure to freshwater (FW; volume loaded,
      salt depleted), saltwater (SW; volume depleted, salt loaded), or freshwater trout
      fed a high-salt diet (FW-HSD; volume and salt loaded). We also measured NP
      transcriptional response to acute (2 h) volume expansion with dialyzed plasma
      (VE; 80% blood vol) or volume depletion by hemorrhage (VD, 20% blood volume every
      30 min for 2 h) with real-time PCR. In essentially all instances, increased
      expression of the NP system was associated with FW-HSD or plasma expansion. There
      were no differences in NP expression between chronically adapted FW and SW fish,
      and hemorrhage decreased atrial ANP and VNP mRNA. These results indicate that
      rainbow trout cardiac NPs and cardiovascular GC-NPRs respond principally to
      volume, not salt overload, and this suggests that the primary function of trout
      cardiac NP system is to protect the heart.

PMID- 19176888
TI  - Fetal iron status regulates maternal iron metabolism during pregnancy in the rat.
AB  - Iron metabolism during pregnancy is biased toward maintaining the fetal supply,
      even at the cost of anemia in the mother. The mechanisms regulating this are not
      well understood. Here, we examine iron deficiency and supplementation on the
      hierarchy of iron supply and the gene expression of proteins that regulate iron
      metabolism in the rat. Dams were fed iron-deficient diets for 4 wk, mated, and
      either continued on the deficient diet or an iron-supplemented diet during either
      the first half or the second half of their pregnancy. A control group was
      maintained on normal iron throughout. They were killed at 0.5, 12.5, or 21.5 days
      of gestation, and tissues and blood samples were collected. Deficiency and
      supplementation had differential effects on maternal and fetal hematocrit and
      liver iron levels. From early in pregnancy, a hierarchy of iron supply is
      established benefiting the fetus to the detriment of the mother. Transferrin
      receptor, transferrin receptor 2, and hepcidin mRNA expression were regulated by
      both iron deficiency and supplementation. Expression patterns showed both organ
      and supplementation protocol dependence. Further analysis indicated that iron
      levels in the fetal, and not maternal, liver regulate the expression of liver
      transferrin receptor and hepcidin expression in the mother.

PMID- 19176887
TI  - COX-2 inhibitor reduces skeletal muscle hypertrophy in mice.
AB  - Anti-inflammatory strategies are often used to reduce muscle pain and soreness
      that can result from high-intensity muscular activity. However, studies indicate
      that components of the acute inflammatory response may be required for muscle
      repair and growth. The hypothesis of this study was that cyclooxygenase (COX)-2
      activity is required for compensatory hypertrophy of skeletal muscle. We used the
      synergist ablation model of skeletal muscle hypertrophy, along with the specific
      COX-2 inhibitor NS-398, to investigate the role of COX-2 in overload-induced
      muscle growth in mice. COX-2 was expressed in plantaris muscles during
      compensatory hypertrophy and was localized mainly in or near muscle cell nuclei.
      Treatment with NS-398 blunted the increases in mass and protein content in
      overloaded muscles compared with vehicle-treated controls. Additionally, the COX
      2 inhibitor decreased activity of the urokinase type plasminogen activator,
      macrophage accumulation, and cell proliferation, all of which are required for
      hypertrophy after synergist ablation. Expression of insulin-like growth factor-1
      and phosphorylation of Akt, mammalian target of rapamycin, and p70S6K were
      increased following synergist ablation, but were not affected by NS-398.
      Additionally, expression of atrogin-1 was reduced during hypertrophy, but was
      also not affected by NS-398. These results demonstrate that COX-2 activity is
      required for skeletal muscle hypertrophy, possibly through facilitation of
      extracellular protease activity, macrophage accumulation, and cell proliferation.

PMID- 19176889
TI  - Swelling-activated transport of taurine in cultured gill cells of sea bass:
      physiological adaptation and pavement cell plasticity.
AB  - We have investigated volume-activated taurine transport and ultrastructural
      swelling response of sea bass gill cells in culture, assuming that euryhaline
      fish may have developed particularly efficient mechanisms of salinity adaptation.
      In vivo, when sea basses were progressively transferred from seawater to
      freshwater, we noticed a decrease in blood osmotic pressure. When gill cells in
      culture were subjected to 30% hypotonic shock, we observed a five-fold
      stimulation of [(3)H]taurine efflux. This transport was reduced by various anion
      channel inhibitors with the following efficiency: 5-nitro-2-(3
      phenylpropylamino)benzoic acid (NPPB) > niflumic acid > DIDS = diphenylamine-2
      carboxylic acid. With polarized gill cells in culture, the hypotonic shock
      produced a five-fold stimulation of apical taurine transport, whereas basolateral
      exit was 25 times higher. Experiments using ionomycin, thapsigargin, BAPTA-AM, or
      removal of extracellular calcium suggested that taurine transport was regulated
      by external calcium. The inhibitory effects of lanthanum and streptomycin support
      Ca(2+) entry through mechanosensitive Ca(2+) channels. Branchial cells also
      showed hypotonically activated anionic currents sensitive to DIDS and NPPB.
      Similar pharmacology and time course suggested the potential existence of a
      common pathway for osmosensitive taurine and Cl(-) efflux through volume
      sensitive organic osmolyte and anion channels. A three-dimensional structure
      study revealed that respiratory gill cells began to swell only 15 s after
      hypoosmotic shock. Apical microridges showed membrane outfoldings: the cell
      surface became smoother with a progressive disappearance of ridges. Therefore,
      osmotic swelling may not actually induce membrane stretch per se, inasmuch as the
      microridges may provide a reserve of surface area. This work demonstrates
      mechanisms of functional and morphological plasticity of branchial cells during
      osmotic stress.

PMID- 19176890
TI  - Glycemic control prevents microvascular remodeling and increased tone in type 2
      diabetes: link to endothelin-1.
AB  - Medial thickening and vascular hypertrophy of resistance arteries can lead to
      cardiovascular complications associated with diabetes. While previous studies
      have established a role of type 1 diabetes in vascular remodeling, we recently
      extended these observations to type 2 diabetes and reported increased collagen
      deposition due to alterations in matrix metalloproteinase expression and activity
      in mesenteric resistance arteries. These studies also showed that remodeling
      response was mediated by endothelin-1 (ET-1) via activation of ET(A) receptors,
      whereas blockade of ET(B) receptors exacerbated the remodeling. However, the
      effectiveness of glycemic control strategies in preventing these vascular
      changes, including activation of the ET system still remained unclear. Also, very
      little is known about whether and to what extent reorganization of the
      extracellular matrix (ECM) affects vascular compliance and vasomotor tone.
      Accordingly, this study assessed structural remodeling of mesenteric
      microvessels, vascular compliance, and myogenic tone, as well as the role of
      matrix metalloproteinases (MMP) in mediating these processes. Spontaneously
      diabetic, non-obese Goto-Kakizaki (GK) rats, a model for type 2 diabetes, and
      normoglycemic Wistar rats were used for the studies. A subset of GK rats were
      administered metformin to achieve euglycemia. Glycemic control normalized the
      increased media-to-lumen ratios (M/L) and myogenic tone seen in diabetes, as well
      as normalizing plasma ET-1 levels and mesenteric ET(A) receptor expression. There
      was increased collagen synthesis in diabetes paralleled by decreased collagenase
      MMP-13 activity, while glycemic control attenuated the process. These findings
      and our previous study taken together suggest that hyperglycemia-mediated
      activation of ET-1 and ET(A) receptors alter vascular structure and mechanics in
      type 2 diabetes.

PMID- 19176892
TI  - Changing expression patterns: focus on "the transcription factor, glial cell
      missing 2, is involved in differentiation and functional regulation of H+-ATPase
      rich cells in zebrafish (Danio rerio)".

PMID- 19176891
TI  - Phenotype of neurons in the nucleus of the solitary tract that express CCK
      induced activation of the ERK signaling pathway.
AB  - The satiating potency of CCK has been well characterized, including its mediation
      by capsaicin-sensitive vagal primary afferents. We have previously shown that
      peripherally administered CCK activates the MAPK-signaling cascade in a
      population of nucleus of the solitary tract (NTS) neurons and that preventing
      ERK1/2 phosphorylation partly attenuates CCK's satiating potency. The aim of this
      study was to identify the neurochemical phenotypes of the NTS neurons that
      exhibit CCK-induced activation of ERK1/2. Using confocal microscopy, we
      demonstrate that intraperitoneal CCK administration increases the number of
      neurons that express phosphorylated ERK1/2 (pERK1/2) in the medial and
      commissural subnuclei of the NTS and that CCK-induced expression of ERK1/2 is
      increased in tyrosine hydroxylase-immunoreactive neurons. Using Western blot
      analysis, we show that the robust increase in tyrosine hydroxylase
      phosphorylation obtained with intraperitoneal CCK is significantly attenuated in
      rats pretreated with the ERK-pathway blocker U0126 injected into the 4th
      ventricle. In addition, CCK injections increased pERK1/2 expression in POMC
      neurons in the NTS. In contrast, only the rare GAD67, neuronal nitric oxide
      synthase, and leptin-responsive neuron exhibited CCK-induced pERK
      immunoreactivity. We conclude that activation of POMC-immunoreactive neurons and
      tyrosine hydroxylase activity via the ERK-signaling pathway in the NTS likely
      contributes to CCK's satiating effects.

PMID- 19176893
TI  - Cracking the therapeutic nut in mild cognitive impairment: better nuts and better
      nutcrackers.

PMID- 19176894
TI  - SOD1 A4V familial ALS in North America: can understanding the past lead to a
      better future?

PMID- 19176895
TI  - Donepezil treatment of patients with MCI: a 48-week randomized, placebo
      controlled trial.
AB  - BACKGROUND: Treatment of mild cognitive impairment (MCI) with cholinesterase
      inhibitors may improve symptoms. METHODS: In this multicenter, randomized,
      placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in
      period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then
      10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included
      change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive
      subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB)
      after 48 weeks of treatment (modified intention-to-treat analysis). Secondary
      efficacy measures evaluated cognition, behavior, and function. RESULTS: The dual
      primary efficacy endpoint was not reached. We noted a small, but significant,
      decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint.
      Little change from baseline in CDR-SB and secondary variables was observed for
      either group. Patient Global Assessment scores favored donepezil at all time
      points except week 12 (p < or = 0.05). Perceived Deficits Questionnaire scores
      favored donepezil at week 24 (p = 0.05). Clinical Global Impression of Change-MCI
      scores favored donepezil only at week 6 (p = 0.04). Adverse events were generally
      mild or moderate. More donepezil-treated subjects (18.4%) discontinued treatment
      due to adverse events than placebo-treated subjects (8.3%). CONCLUSIONS:
      Donepezil demonstrated small but significant improvement on the primary measure
      of cognition but there was no change on the primary measure of global function.
      Most other measures of global impairment, cognition, and function were not
      improved, possibly because these measures are insensitive to change in MCI.
      Responses on subjective measures suggest subjects perceived benefits with
      donepezil treatment.

PMID- 19176896
TI  - Age and founder effect of SOD1 A4V mutation causing ALS.
AB  - BACKGROUND: The alanine to valine mutation at codon 4 (A4V) of SOD1 causes a
      rapidly progressive dominant form of amyotrophic lateral sclerosis (ALS) with
      exclusively lower motor neuron disease and is responsible for 50% of SOD1
      mutations associated with familial ALS in North America. This mutation is rare in
      Europe. The authors investigated the origin (geographic and time) of the A4V
      mutation. METHODS: Several cohorts were genotyped: North American patients with
      confirmed A4V mutation (n = 54), Swedish (n = 3) and Italian (n = 6) A4V
      patients, patients with ALS with SOD1 non-A4V mutations (n = 66) and patients
      with sporadic ALS (n = 96), healthy white (n = 96), African American (n = 17),
      Chinese (n = 53), Amerindian (n = 11), and Hispanic (n = 12) subjects. High
      throughput SNP genotyping was performed using Taqman assay in 384-well format. A
      novel biallelic CA repeat in exon 5 of SOD1, tightly linked to A4V, was genotyped
      on sequencing gels. Association statistics were estimated using Haploview. p
      Values less than 0.05 were considered significant. Age of A4V was estimated using
      a novel method based on r(2) degeneration with genetic distance and a Bayesian
      method incorporated in DMLE+. RESULTS: A single haplotype of 10 polymorphisms
      across a 5.86-cM region was associated with A4V (p = 3.0e-11) when white controls
      were used, suggesting a founder effect. The strength of association of this
      haplotype progressively decreased when African American, Chinese, Hispanic, and
      Amerindian subjects were used as controls. The associated European haplotype was
      different from the North American haplotype, indicating two founder effects for
      A4V (Amerindian and European). The estimated age of A4V with the r(2)
      degeneration method was 458 +/- 59 years (range 398-569) and in agreement with
      the Bayesian method (554-734 years with 80-90% posterior probability).
      CONCLUSIONS: North American SOD1 alanine to valine mutation at codon 4 descended
      from two founders (Amerindian and European) 400-500 years ago.

PMID- 19176897
TI  - Creating change: using the arts to help stop the stigma of mental illness and
      foster social integration.
AB  - Stigma is a social justice problem that plagues persons with psychiatric
      disabilities, their families, and society. It fuels the fear underlying
      discrimination; undermines consumer self-efficacy; and blocks rehabilitation,
      recovery, and social integration. The author hopes to create a passion for change
      and suggest a way that everyone can help stop stigma. This approach is simple: to
      nurture the artistic talent many clients possess and connect them with public
      venues for their artworks. On display, too, will be the "ability" in
      "disability." This will reduce stigma while building self-efficacy and
      empowerment. Anecdotal evidence supports this hypothesis. However, research is
      needed; a design for a study to test this hypothesis is described. Significantly,
      an antistigmal arts intervention can be conducted by any aware practitioner; one
      does not need to be an art therapist or have any background in art, only a desire
      to make a difference and resources on which to draw.

PMID- 19176898
TI  - The brief serenity scale: a psychometric analysis of a measure of spirituality
      and well-being.
AB  - PURPOSE: This article describes a factor analysis of a 22-item version of the
      Serenity Scale, a tool that measures spirituality and well-being. METHOD: A
      sample of 87 participants, enrolled in a National Institutes of Health-funded
      clinical trial examining the impact of mindfulness-based stress reduction on
      symptom management post-solid organ transplantation, completed the abbreviated
      instrument. FINDINGS: Exploratory factor analysis yielded three subscales:
      acceptance, inner haven, and trust. The Serenity Scale was positively associated
      with positive affect and mindful awareness and inversely related to negative
      affect, anxiety, depression, health distress and transplant-related stress.
      CONCLUSIONS: Serenity, a dimension of spirituality that is secular and distinct
      from religious orientation or religiosity, shows promise as a tool that could be
      used to measure outcomes of nursing interventions that improve health and well
      being. IMPLICATIONS: Spirituality is recognized as being an essential component
      of holistic nursing practice. As nurses expand their use of spiritual
      interventions, it is important to document outcomes related to nursing care. The
      Serenity Scale appears to capture a dimension of spirituality, a state of
      acceptance, inner haven and trust that is distinct from other spirituality
      instruments.

PMID- 19176899
TI  - Existential and spiritual needs in mental health care: an ethical and holistic
      perspective.
AB  - This study illuminates how existential needs and spiritual needs are connected
      with health care ethics and individuals' mental health and well-being. The term
      existential needs is defined as the necessity of experiencing life as meaningful,
      whereas the term spiritual needs is defined as the need of deliverance from
      despair, guilt and/or sin, and of pastoral care. It discusses whether or not
      patients' needs are holistically addressed in Western health care systems that
      neglect patients' existential and spiritual needs, because of their biomedical
      view of Man which recognizes only patients' physical needs. It excludes a
      holistic health care which considers all needs, expressed by patients in
      treatment of mental illness. Addressing all needs is important for patients'
      improvement and recovery. For some patients, this is the only way to regain their
      mental health and well-being.

PMID- 19176900
TI  - The provision of spiritual care by registered nurses on a maternal-infant unit.
AB  - PURPOSE: This study explores the spirituality, spiritual well-being (SWB), and
      spiritual care provision of registered nurses on a maternal-infant unit. METHODS:
      Data collection instruments included a demographic and spiritual care form,
      Spiritual Perspective Scale (SPS), and Spiritual Well-Being Scale (SWBS) to
      address the study's research questions. FINDINGS: Significant positive
      correlations were found between SPS and SWBS as well as religious well-being
      (RWB) and existential well-being (EWB; subscales of SWBS). Religious attendance
      was significantly correlated with SPS, SWBS, and RWB but not EWB. Frequency of
      spiritual assessment themes was first encounter and when needed, whereas reaching
      up and reaching out described their provision of spiritual care. CONCLUSION: The
      sample was highly spiritual, spiritually well, and provided varied spiritual
      care. IMPLICATIONS: More spiritual care research is needed. Content on providing
      spiritual care must be enhanced within nursing curricula as well as with nurses
      in practice.

PMID- 19176944
TI  - Elevated plasma chromogranin A is the first indication of recurrence in radically
      operated midgut carcinoid tumors.
AB  - BACKGROUND: Patients with malignant midgut carcinoids are occasionally diagnosed
      with limited tumor spread, and surgery with radical intention is performed.
      Despite curative intent, recurrences occur frequently, motivating long-term
      biochemical and radiological follow-up. This study aimed to compare the
      usefulness of various methods in detecting such recurrences. METHODS: This
      retrospective study included 56 patients with radically operated midgut
      carcinoids referred to our University Hospital for evaluation and follow-up
      between 1985 and 2004. Patients were monitored 1-3 times per year using plasma
      chromogranin A (P-CgA), urinary 5-hydroxyindoleacetic acid (U-5HIAA)
      concentrations as well as radiological examinations, including ultrasonography,
      computerized tomography or magnetic resonance investigation. In a subset of
      cases, somatostatin receptor scintigraphy and/or positron emission tomography
      with 5-hydroxytryptophan was performed. Time from operation until established
      recurrence was recorded. RESULTS: Tumor recurrence was established in 33 of 56
      patients after a median of 32 months (range 6-217). Elevated P-CgA was the first
      marker to become pathologically elevated in 28 of these 33 patients (85%). In 3
      of these 28 patients, radiology was simultaneously positive for a recurrence.
      CONCLUSION: P-CgA was the first marker to indicate tumor recurrence in the
      majority of radically operated midgut carcinoid patients. To avoid unnecessary
      and costly examinations in asymptomatic patients, we suggest that follow-up
      should comprise measurements of P-CgA twice a year and annual ultrasonography
      until P-CgA is elevated or clinical symptoms occur, at which time all efforts
      should be made to identify recurrent tumor lesions in order to give the patient
      the best possible treatment which, if possible, should be surgical removal of the
      recurrence.

PMID- 19176945
TI  - Body mass index and body composition in adolescents treated with gonadotropin
      releasing hormone analogue triptorelin depot for central precocious puberty: data
      at near final height.
AB  - BACKGROUND/AIM: In children with central precocious puberty (CPP), gonadotropin
      releasing hormone (GnRH) analogue treatment has been associated with an increase
      in body mass index (BMI). We evaluated BMI and body composition in adolescents
      treated with GnRH analogue at their near final height to assess the long-term
      effects of therapy on these parameters. PATIENTS AND METHODS: We studied 20
      patients (14.8 +/- 1.6 years; 17 females) previously treated with triptorelin
      depot for CPP (3.75 mg/28 days) from 8.1 +/- 0.8 to 11.5 +/- 0.8 years. 23
      healthy adolescents with normal onset of puberty (14.7 +/- 2.1 years, 19 females)
      were the controls. BMI and body composition (dual-energy x-ray absorptiometry)
      were assessed. RESULTS: Patients reached their near adult height (-0.5 +/- 1.1
      standard deviation score (SDS)); the girls were menstruating and the majority
      (15/17) had regular cycles, the boys showed normal testicular function. BMI was
      unchanged from the start of GnRH analogue therapy (0.4 +/- 1.0 SDS) to near adult
      height (0.2 +/- 1.0 SDS, p = NS vs. 0). Total fat mass (TFM) was significantly
      increased (16,144 +/- 8,065 g; controls 10,712.1 +/- 4,120.4 g, p < 0.02);
      glucose homeostasis and lipid profile corresponded to reference ranges.
      CONCLUSIONS: GnRH analogue therapy did not show long-term detrimental effects on
      BMI, but it may increase TFM, suggesting that body composition should be
      monitored till adulthood.

PMID- 19176946
TI  - Long-term intracerebroventricular infusion of insulin, but not glucose, modulates
      body weight and hepatic insulin sensitivity by modifying the hypothalamic insulin
      signaling pathway in type 2 diabetic rats.
AB  - BACKGROUND/AIMS: It has been reported that the short-term injection of insulin
      and glucose into the hypothalamus modulates body weight and hepatic glucose
      production in non-diabetic rats. However, the effect of hypothalamic insulin and
      glucose on peripheral glucose metabolism in diabetic animals remains uncertain.
      We investigated how intracerebroventricular (ICV) infusion of insulin and glucose
      modified body weight and peripheral glucose homeostasis in 90% pancreatectomized
      rats that exhibited symptoms of mild and non-obese type 2 diabetes. METHODS: The
      diabetic rats that were fed a high fat diet were ICV administered with either
      insulin (0.3 U/day), glucose (10 mg/day), insulin plus glucose (insulin+glucose),
      or artificial cerebrospinal fluid (control) by means of osmotic pumps for 4
      weeks. RESULTS: Central insulin and insulin+glucose reduced body weight with a
      slight decrease of food intake compared to the control and glucose groups in
      diabetic rats. In addition, during euglycemic hyperinsulinemic clamp, ICV
      infusion of insulin and insulin+glucose increased glucose infusion rates and
      decreased hepatic glucose production compared to the control and glucose groups.
      The improvement of insulin sensitivity was associated with the activation of both
      hypothalamic and hepatic insulin signaling cascades. Central glucose did not
      affect hypothalamic insulin action in diabetic rats. CONCLUSION: Long-term
      central infusion of insulin enhanced energy metabolism and hepatic glucose
      homeostasis in type 2 diabetic rats partly via potentiating hypothalamic insulin
      signaling. However, central glucose infusion did not modulate the central and
      peripheral metabolism.

PMID- 19176947
TI  - Capillary supply of the soft palate muscles is reduced in long-term habitual
      snorers.
AB  - BACKGROUND: Snoring and obstructive sleep apnea (OSA) cause vibration and stretch
      of the upper airway tissues that may result in neuromuscular damage and changes
      in the microcirculation. OBJECTIVES: The aim of this investigation was to test
      whether long-term snoring affects capillary supply in soft palate muscles.
      METHODS: Samples from the palatopharyngeus (PP) and uvula (UV) muscles were
      collected from 8 patients undergoing uvulo-palatopharyngoplasty because of
      habitual snoring and OSA. Control samples were obtained at autopsy. The muscles
      were analyzed using immunohistochemistry and morphometry. RESULTS: The patients'
      palate muscles had a lower capillary density (PP 443 vs. 711 capillaries/mm(2), p
      < 0.001, and UV 452 vs. 624 capillaries/mm(2), p = 0.009), a lower number of
      capillaries related to an individual muscle fiber (PP 1.3 vs. 2.7, p = 0.003, and
      UV 1.0 vs. 1.9, p = 0.03) and a lower number of capillaries related to the fiber
      size (PP 0.9 vs. 2.1, p = 0.001, and UV 0.6 vs. 1.9, p = 0.002). CONCLUSIONS: Our
      results indicate that reduced capillary supply of palate muscles plays a
      pathophysiological role in long-term snorers and OSA. The cause of the low
      capillary supply is unclear, but neuromuscular injury due to repeated vibratory
      and stretch trauma of the soft palate during snoring is a plausible mechanism.

PMID- 19176948
TI  - Isolated limb infusion as a novel treatment for extensive plantar warts.
AB  - BACKGROUND: We describe the previously unreported use of isolated limb infusion
      (ILI) to treat extensive, bilateral plantar warts in a 54-year-old female. The
      warts had covered the weight-bearing surfaces of both feet for 10 years and had
      failed to respond to all previous treatments. METHODS: A standard ILI technique
      was used to infuse melphalan and actinomycin D to the left leg. Circulation was
      maintained for 30 min. The limb was warmed and upon completion of the procedure
      was markedly hypoxic and acidotic. The contralateral limb was treated 6 months
      later. RESULTS: At 5 weeks, a partial response with 80% disease clearance was
      observed. Pain impeded mobilisation until desquamation occurred 6 weeks
      postoperatively. There was little regrowth at 6 months. CONCLUSION: Although
      invasive, ILI may represent a viable treatment option for resistant human
      papilloma virus-induced warts on the peripheries. Further research into this
      potential treatment tool is warranted.

PMID- 19176949
TI  - Successful prevention of cuffed hemodialysis catheter-related infection using an
      antibiotic lock technique by strictly catheter-restricted antibiotic lock
      solution method.
AB  - BACKGROUND: Catheter-related infection (CRI) is associated with increased all
      cause mortality and morbidity in hemodialysis patients and may be reduced by
      using antimicrobial lock solutions. But the safety of long-term use of
      antimicrobial lock still needs to be defined. METHODS: Patients with a new
      inserted permanent tunneled cuffed hemodialysis catheter were randomly assigned
      to an antibiotic lock solution of gentamicin (4 mg/ml) heparin (G group) or
      heparin alone (H group). RESULTS: A total of 140 patients were enrolled in this
      study. CRI rates were 0.06/1,000 catheter-days for the G group versus 0.67 in the
      H group (p = 0.014). The risk of CRI was 10.54 higher in patients with a heparin
      alone locked catheter (p = 0.025) than that with gentamicin. The serum-measured
      gentamicin levels were very low. CONCLUSIONS: Gentamicin lock solution reduces
      CRI and improves catheter survival rates in hemodialysis patients. It is
      relatively safe in strictly catheter-restricted antibiotic lock solution therapy.

PMID- 19176950
TI  - Access blood flow and the risk of complications in mature forearm and upper arm
      arteriovenous fistulas.
AB  - BACKGROUND/AIMS: Optimization of vascular access use in the 'fistula first' era
      requires comprehension of its clinical behavior. Little is known about mature
      arteriovenous fistula (AVF) performance and the role of fistula location. Widely
      used access flow (Qa) was used to analyze complication risks and functionality
      after first hemodialysis use. METHODS: 178 Mature AVFs were analyzed.
      Complication was defined as permanent failure or >or=1 intervention. Factors
      associated with complications and mean Qa were determined using Cox proportional
      hazards and linear regression models. RESULTS: Baseline Qa was significantly
      lower in complicated versus uncomplicated forearm and upper arm AVFs. In
      complicated forearm AVFs, preoperative arterial diameter was smaller while the
      risk of complications was graded per 100 ml/min baseline Qa increase. Diabetics
      had an increased risk of upper arm AVF complications. In uncomplicated forearm
      AVFs, diabetes was related to lower mean Qa, and BMI to higher Qa. CONCLUSIONS:
      In mature AVFs, baseline Qa depends on fistula location and is related to the
      risk of complications in a graded manner.

PMID- 19176951
TI  - Phosphate - the silent stealthy cardiorenal culprit in all stages of chronic
      kidney disease: a systematic review.
AB  - BACKGROUND AND AIM: Due to increasing evidence suggesting a link between
      hyperphosphatemia and cardiovascular disease (CVD), mediated through vascular
      calcification in patients on dialysis, the following question arises: At what
      stage of chronic kidney disease (CKD) does the relationship between elevated
      phosphate levels, vascular calcification and increased cardiovascular mortality
      begin? Therefore, the purpose of the current study was to critically review the
      current literature regarding this issue. METHODS: We performed a systematic
      search of the National Library of Medicine and the Cochrane Library databases
      from January 1985 to February 2008 to identify clinical studies examining the
      effects of plasma phosphate on cardiovascular outcome, mortality and progression
      of kidney disease in subjects with and without CKD who have not yet received
      dialysis. The primary outcome measure was the development of CVD, mortality and
      progression of kidney disease. RESULTS: Twelve clinical trials investigated the
      role of serum phosphate levels and adverse outcome (9 studies examining CVD
      outcome and 3 examining progression of kidney disease). After adjustment for risk
      factors for mortality, adverse cardiovascular outcome and progression of kidney
      disease, all studies found a graded independent significant association between
      phosphate levels and mortality, development of CVD and progression of kidney
      disease. There was no such association with plasma calcium levels. CONCLUSIONS:
      There is a graded independent association between serum phosphate levels and
      mortality, mainly cardiovascular events, and the progression of renal disease in
      subjects with and without definable (loss of glomerular filtration rate) CKD.

PMID- 19176952
TI  - Classification of minor stroke: intra- and inter-observer reliability.
AB  - BACKGROUND: The Oxfordshire Community Stroke Project (OCSP) and Trial of ORG
      10172 in Acute Stroke Treatment (TOAST) classifications are widely used for the
      assessment of major ischaemic stroke. We explored their intra- and inter-observer
      reliability in the classification of outpatient minor stroke. METHODS: Four
      physicians of differing seniority and training backgrounds classified minor
      stroke using clinical data from 90 patients. RESULTS: For both the OCSP and TOAST
      classifications, the intra-observer reliability varied from moderate to excellent
      (kappa = 0.48-0.83). The inter-observer reliability was good (kappa = 0.64) for
      the OCSP and moderate (kappa = 0.42) for the TOAST. Thus, neither classification
      was consistently reliable. CONCLUSIONS: Our results may reflect the limited
      validity of these classifications in a typical minor stroke outpatient population
      and variable observer expertise.

PMID- 19176953
TI  - Paracentral strip infarcts of the middle cerebral artery: borderzone ischaemia or
      cortical artery occlusion?
AB  - BACKGROUND AND PURPOSE: We have noted the presence of small strip-like infarcts
      involving the cortex within the interdivisional territory of the middle cerebral
      artery (MCA) and sometimes extending to the periventricular region. The incidence
      in a stroke unit population, mechanisms, clinical expression and prognosis of
      patients with these cortical infarcts are unknown. To clarify these issues we
      retrospectively and prospectively identified these patients in our own stroke
      unit population. METHODS: Patients were identified retrospectively and
      prospectively from the Austin Hospital Stroke Unit from March 2001 to May 2007.
      All were selected on the basis of the recent onset of an acute neurological
      deficit with imaging showing strip infarction within the MCA territory. Clinical
      features were recorded and the mechanism of infarction was classified based on
      the TOAST criteria from standard investigations. RESULTS: From 4,274 acute stroke
      admissions, there were 24 patients (0.6%), 12 males and 12 females (mean age 75
      years; range 44-92 years) with CT or MRI showing characteristic linear infarction
      in the middle cerebral territory. In most cases, infarction was adjacent to the
      central sulcus. Common clinical features included mild-to-moderate hemiparesis
      with cortical signs. The most common TOAST criterion mechanism categories were
      artery-to-artery or cardiac embolism. It is postulated that this resulted in
      either isolated small cortical artery branch occlusion or borderzone infarction
      between superior and inferior divisions of the MCA due to more proximal large
      artery vessel occlusion. Prognosis was good. CONCLUSIONS: We describe the
      phenotypic expression, postulated mechanisms and prognosis of strip-like infarcts
      between the superior and inferior MCA divisions. The likely artery-artery or
      cardio-embolic mechanisms should prompt clinicians to search for an embolic
      source. While the prognosis of the syndrome is generally good, its recognition
      may allow specific therapies to be developed to improve clinical outcomes
      further.

PMID- 19176954
TI  - Safety and efficacy of MRI-based selection for recombinant tissue plasminogen
      activator treatment: responder analysis of outcome in the 3-hour time window.
AB  - INTRODUCTION: The use of MRI may alter the target population for intravenous
      recombinant tissue plasminogen activator (rtPA) treatment relative to
      conventional CT. If selection changes, it remains crucial to demonstrate safety
      and efficacy of rtPA for the overall population, as well as in subpopulations
      hypothesized to benefit from MRI. MATERIALS AND METHODS: Clinical outcome and
      incidence of symptomatic intracerebral hemorrhage (ICH) was recorded in 112
      consecutive patients treated with intravenous rtPA (0-3 h) with MRI as first
      choice imaging modality. According to the responder analysis, favorable outcome
      was separately defined for mild (NIHSS <8; n = 51), moderate (NIHSS 8-14; n = 30)
      and severe (NIHSS >14; n = 31) stroke. RESULTS: Eighty-three patients were
      treated with rtPA after MRI, and 29 after CT. Adjusted for baseline severity, 42%
      of all patients had a favorable outcome, compared to 37% in NINDS. Among patients
      with severe stroke, MR-selected patients showed a good outcome in 52% of patients
      compared to 29% in NINDS (p < 0.05). Symptomatic ICH occurred in 2 patients (1.9
      %), and 7 patients died during hospitalization (6.3%). CONCLUSION: MRI-based rtPA
      is safe and time-efficient. Outcome data compares well with NINDS data.
      Diagnostic information obtained from multimodal MRI may affect the target group.
      Our data support the hypothesized benefit of MRI in patients with severe stroke.

PMID- 19176955
TI  - Contrast transcranial Doppler can diagnose large patent foramen ovale.
AB  - BACKGROUND: Contrast transesophageal echocardiography (c-TEE) and contrast
      transcranial Doppler (c-TCD) are useful diagnostic tools for detecting right-to
      left shunts (RLS). However, the diagnostic accuracy of c-TCD for patent foramen
      ovale (PFO) remains uncertain. We investigated the relationship between the size
      of PFO determined by c-TEE and c-TCD findings and assessed the detectable rate of
      RLS by c-TCD. METHODS: We assessed RLS three times using simultaneous c-TCD and c
      TEE in 107 patients (321 examinations). We classified all of ultrasound
      examinations into three groups by size according to microbubbles on c-TEE, such
      as no PFO (0 microbubble), small PFO (1-29 microbubbles) and large PFO (>or=30
      microbubbles). We also calculated the number of microembolic signals (MES) on c
      TCD and evaluated the association between PFO size on c-TEE and MES count on c
      TCD. RESULTS: In the present study, c-TEE detected RLS in 105 (33%; small PFO, n
      = 78; large PFO, n = 27), and c-TCD detected RLS in 49 (15%) of 321 examinations.
      Among 78 examinations with small PFO, MES were found in only 19 (24%) on c-TCD.
      In contrast, of all 27 examinations with large PFO, MES were found on c-TCD.
      Also, c-TCD were able to detect MES in 3 of 216 examinations among the no-PFO
      group. When >or=2 MES on c-TCD was established as the cutoff to predict large PFO
      on c-TEE, the sensitivity, specificity and accuracy were 96.3, 96.8, and 96.9%,
      respectively. CONCLUSION: When two or more MES were determined by c-TCD, large
      PFO could be accurately diagnosed.

PMID- 19176956
TI  - The quality of diabetes care following hospitalization for ischemic stroke.
AB  - BACKGROUND: Follow-up is critically important for stroke survivors with diabetes,
      yet there is limited research about the quality of diabetes care that these
      patients receive. We investigated performance on diabetes quality of care
      indicators for stroke survivors overall and by race. METHODS: Claims data was
      extracted for 1,460 Medicare beneficiaries with preexisting diabetes who survived
      hospitalization for acute ischemic stroke in 2000. Adjusted probabilities of
      receiving HbA1c, LDL and dilated eye exams were estimated using logistic
      regression. RESULTS: 53% had a dilated eye exam, 60% received an LDL check, 73%
      percent had their HbA1c checked at least once and only 51% received two or more
      HbA1c checks. In the unadjusted results, blacks were significantly less likely
      than whites to receive these tests. CONCLUSIONS: Care of stroke survivors,
      particularly blacks, shows gaps according to guidelines.

PMID- 19176957
TI  - Increased prevalence of hyperhomocysteinemia in cervical artery dissection
      causing stroke: a case-control study.
AB  - BACKGROUND: Spontaneous cervical artery dissection (sCAD) is a nonatherosclerotic
      vascular disease of unknown etiology. Mild elevation of total plasma homocysteine
      (tHcy) levels may be a risk factor for sCAD, but the precise mechanism remains
      unknown. On the other hand, mild hyperhomocysteinemia is also associated with
      ischemic stroke related to atherothrombotic or small artery disease. We undertook
      a case-control study to compare the prevalence of mild hyperhomocysteinemia and
      tHcy levels between patients with a first ischemic stroke due to sCAD and healthy
      volunteers, as well as patients with a first ischemic stroke due to
      atherothrombotic or small artery disease. METHODS: Fasting tHcy levels were
      determined in 346 consecutive patients with a first ischemic stroke due to sCAD
      (n = 86) and atherothrombotic or small artery disease (n = 260) within 24 h after
      the onset of symptoms, and in 100 healthy volunteers. RESULTS: Mild
      hyperhomocysteinemia was more prevalent in patients with sCAD causing ischemic
      stroke (n = 33, 38%) than in healthy volunteers (n = 23, 23%; p = 0.034), and
      less prevalent than in patients with ischemic stroke due to atherothrombotic or
      small artery disease (n = 149, 57%; p = 0.001). Mean fasting tHcy levels of
      patients with ischemic stroke caused by sCAD showed a trend to be higher (11.4 +/
      3.8 micromol/l) than those of healthy volunteers (10.2 +/- 3.0 micromol/l, p =
      0.61), but were lower than those of patients with stroke due to atherothrombotic
      or small artery disease (13.6 +/- 6.6 micromol/l, p = 0.002). CONCLUSION: Our
      results suggest that mild hyperhomocysteinemia may be a risk factor for sCAD
      causing ischemic stroke, but further studies are needed to identify a possible
      mechanism. This study confirms the association of hyperhomocysteinemia with
      ischemic stroke due to atherothrombotic or small artery disease.

PMID- 19176958
TI  - Associations of inflammatory and haemostatic biomarkers with poor outcome in
      acute ischaemic stroke.
AB  - BACKGROUND: Many inflammatory and haemostatic biomarkers show associations with
      acute ischaemic stroke outcome, but few studies compare a large range of markers.
      METHODS: We assessed clinical status and 16 biomarkers within 24 h of onset in
      180 consecutive acute ischaemic stroke patients. RESULTS: A total of 94 patients
      had a poor outcome (dead or dependent at 30 days). C-reactive protein (CRP), IL
      6, and fibrin D-dimer showed the strongest univariate associations with poor
      outcome (>2-fold increase; p < 0.01). When all biomarkers were included with
      clinical variables in a multivariable model, only D-dimer (OR 1.54; 95% CI 1.09
      2.17), CRP (OR 1.31; 95% CI 1.03-1.68) and Scandinavian Stroke Scale (OR 0.91;
      95% CI 0.88-0.95) were associated with poor outcome. CONCLUSIONS: D-dimer and CRP
      are independently associated with poor outcome in acute ischaemic stroke. More
      data is required to expand our understanding of these potential relationships
      with outcome.

PMID- 19176959
TI  - Utilization of intravenous tissue plasminogen activator for ischemic stroke: are
      there sex differences?
AB  - BACKGROUND: We evaluated whether there were sex-related differences in the
      administration of intravenous tissue plasminogen activator (IV-tPA) to patients
      with acute ischemic stroke admitted to US academic medical centers. METHODS:
      Medical records were abstracted for consecutive ischemic stroke patients admitted
      to 32 academic medical centers from January through June, 2004, as part of the
      University HealthSystem Consortium Ischemic Stroke Benchmarking Project.
      Multivariate logistic models were used to test for sex-related differences in the
      receipt of IV-tPA with adjustment for demographic and clinical factors. RESULTS:
      The study included 1,234 patients (49% women; mean age 66.6 years; 56% white). IV
      tPA was given to 7% (6.5% of women versus 7.5% of men, p = 0.49). Women and men
      were equally likely to receive IV-tPA in risk-adjusted analyses (OR 1.02, 95% CI
      0.64-1.64). Approximately 77% of women and men who did not receive IV-tPA did not
      meet the 3-hour treatment window or their time of onset was unknown. CONCLUSIONS:
      Women admitted to academic hospitals receive IV-tPA as often as men; however, a
      substantial percentage of both women and men are not arriving within the 3-hour
      time window required for diagnostic assessment and administration of intravenous
      thrombolytic therapy. Additional efforts are needed to improve the rapid
      identification, evaluation and treatment of stroke patients.

PMID- 19176960
TI  - Treatment of early Parkinson's disease. Part 1.
AB  - The management of early Parkinson's disease (PD) involves the treatment of motor
      symptoms and, increasingly, non-motor symptoms. Given the fast pace of clinical
      research in PD, clinicians are faced with the challenge of integrating the latest
      findings into the ongoing care of individual PD patients. Part 1 of this 2-part
      article reviews motor symptom efficacy data for the newest PD treatment options,
      as well as for established therapies. Safety and tolerability data are also
      reviewed. Part 2 of the article reviews key findings relevant to the assessment
      of potential neuroprotective therapies and the treatment of non-motor symptoms.

PMID- 19176961
TI  - Treatment of early Parkinson's disease. Part 2.
AB  - The management of early Parkinson's disease (PD) involves the treatment of motor
      symptoms, and, increasingly, non-motor symptoms. Given the fast pace of clinical
      research in PD, clinicians are faced with the challenge of integrating the latest
      findings into the ongoing care of individual PD patients. Part 1 of this 2-part
      article reviews efficacy and safety data for the newest PD treatment options, as
      well as for established therapies. Part 2 of the article, presented here, reviews
      key data relevant to the assessment of potential neuroprotective therapies and
      the treatment of non-motor symptoms.

PMID- 19176962
TI  - Awareness and knowledge of the clinical practice guideline on Parkinson's disease
      among German neurologists.
AB  - BACKGROUND/AIMS: With increasing diagnostic and therapeutic options of
      Parkinsonian syndromes (PS), evidence-based medicine clinical practice guidelines
      for Parkinson's disease and related disorders have been published. This study
      evaluates the awareness and the knowledge of the German practice guideline for
      Parkinson's disease among neurologists. METHODS: The cross-sectional
      questionnaire-based study was conducted in 2005 in Germany on a survey of 181
      neurologists in private practice. RESULTS: 53.1% (n = 95) of the participants
      specified to be aware of the guideline. A low level of knowledge was reported in
      diagnostic and therapeutic strategies for motor and nonmotor complications
      (including depression and dementia), and in the diagnostic features of atypical
      PS. Neurologists who were aware of the guideline had a significantly better
      knowledge of the different clinical features of idiopathic (94.7 vs. 84.3%; p =
      0.023) versus nonidiopathic (88.3 vs. 77.1%; p = 0.048) PS in general, and
      specifically of multiple system atrophy (54.3 vs. 36.1%; p = 0.016) as well as of
      characteristics concerning increased daytime sleepiness (95.7 vs. 86.7%; p =
      0.032). CONCLUSION: The awareness and the knowledge of the guideline in everyday
      medical practice are still limited. Future interventions for a better
      implementation must include strategies which are suitable to modify behavior
      patterns.

PMID- 19176963
TI  - Deficit of episodic memory: anatomy and related patterns in stroke patients.
AB  - BACKGROUND/AIMS: Despite numerous studies performed in selected populations,
      major uncertainties regarding the anatomy and patterns of episodic memory deficit
      still persist. Such objectives require the analysis of consecutive unselected
      patients with well-delimitated lesions and the use of specific methodology.
      METHODS: Nonaphasic stroke patients (n = 73) referred for cognitive complaints or
      deficits were examined using a standardized neuropsychological battery. Verbal
      episodic memory was assessed by the Grober and Buschke test. RESULTS: Episodic
      memory deficit was related to lesions of medial temporal, thalamic, frontal,
      lenticular, and centrum semiovale regions, with a left hemisphere predominance.
      Although not specific, an immediate recall deficit was frequently observed in
      thalamic lesions (OR: 5.2, 95% CI: 1.09-24.9). False recognitions (OR: 25.7, 95%
      CI: 2.7-249) and efficiency of cued recall (OR: 8.6, 95% CI: 1.3-57) were highly
      specific of frontal damage. When combined with the usual 'frontal lobe' tests,
      this pattern of memory disorder was an independent predictor (OR: 36, 95% CI: 4.3
      302) and increased the sensitivity of diagnosis of frontal damage (sensitivity:
      0.92, specificity: 0.89). CONCLUSIONS: This study extends the classical anatomy
      of episodic verbal memory. In addition, the 'frontal memory pattern' was found to
      be relatively specific and to be an independent predictor of frontal damage.

PMID- 19176964
TI  - Short-term effects of prolonged fasting on multiple sclerosis.
AB  - Fasting during Ramadan is mandatory for all healthy Muslim adults. During the
      fasting month, many physiological and biochemical changes occur that may be due
      to alterations in eating and sleeping patterns. A concern for Muslim multiple
      sclerosis (MS) patients is whether prolonged fasting might have an unfavorable
      impact on the course of their disease. The aim of this prospective study was to
      determine the effects of prolonged intermittent fasting on the course of MS in a
      cohort of patients who reside in Isfahan, Iran. The cohort consisted of 40 adult
      MS patients who fasted during Ramadan and 40 MS patients who did not fast. Only
      patients with mild disability (expanded disability status scale (EDSS) score
      </=3) were included. All patients were followed for 6 months after Ramadan to
      assess their EDSS score changes and to record the number of clinical relapses. At
      the end of the study, no significant changes in EDSS or the frequency of clinical
      relapses were detected between the 2 groups (p > 0.05). Fasting had no short-term
      unfavorable effects on the disease course in MS patients with mild disability.
      However, larger multi-center prospective studies of longer duration are needed to
      validate the results of this study.

PMID- 19176965
TI  - Efficacy and safety of levetiracetam (3,000 mg/Day) as an adjunctive therapy in
      Chinese patients with refractory partial seizures.
AB  - AIM: To evaluate the efficacy and safety of 3,000 mg daily levetiracetam (LEV;
      Keppra) as an adjunctive therapy for Chinese patients with refractory partial
      seizures. METHODS: This randomized, placebo-controlled trial consisted of an 8
      week baseline period followed by a 4-week titration interval and a 12-week
      maintenance period, and concluded with a 4-week medication withdrawal period or
      entered an open-label study. LEV was compared with placebo. RESULTS: The 50%
      responder rate (the proportion of patients with a minimum of 50% reduction in
      partial seizure frequency) occurred in 46.4% of the LEV group, compared with
      39.3% of the placebo group (p = 0.590). The median of the absolute weekly
      frequency reduction from baseline of partial seizures was 0.66 per week for LEV
      versus 0.48 per week for placebo (p = 0.187). The most common treatment-emergent
      adverse events, mostly mild to moderate in severity, were somnolence, dizziness
      and agitation. CONCLUSION: In this study, adjunctive therapy with LEV 3,000 mg
      daily was well tolerated but not as effective as expected in controlling partial
      seizures in this study population. Considering the lower mean weight of this
      study population, we suggest the dosage of LEV 3,000 mg daily may contribute to
      the results.

PMID- 19176966
TI  - Maxillary sinus grafting with a nano-structured biomaterial: preliminary clinical
      and histological results.
AB  - BACKGROUND: In this study the potential of a new and entirely synthetic, nano
      structured hydroxyapatite-based biomaterial for sinus floor augmentation is
      evaluated. METHODS: 20 sinus floor elevations were carried out in a total of 20
      patients. After a healing period of 6 months, in 10 cases cylinder-shaped bone
      biopsies were taken from the augmented maxillary region using trephine burs.
      RESULTS: The healing period progressed without any complications. General and
      specific histological analysis of the bone biopsies showed a high osteoclast
      activity at the margin of the biomaterial which was well integrated into the
      newly formed bone. CONCLUSION: This study demonstrates that new trabecular bone
      is formed after grafting with the nanocrystalline bone substitute after 6 months.
      Ongoing histomorphological studies are necessary to quantify the biomaterial-bone
      ratio and the exact amount of newly built bone in the augmented cavity after 6
      months.

PMID- 19176967
TI  - Er:YAG laser osteotomy: preliminary clinical and histological results of a new
      technique for contact-free bone surgery.
AB  - BACKGROUND: The purpose of this retrospective study was to evaluate the surgical
      performance, clinical usability and outcome of a new variable square pulsed (VSP)
      Er:YAG laser for bone cutting in oral and maxillofacial surgery. MATERIALS AND
      METHODS: In 40 patients an Er:YAG laser with pulse energy of 1,000 mJ, pulse
      duration of 300 mus and a frequency of 12 Hz was used for different intraoral
      osteotomies. The spot size was 0.9 mm, and the handpiece was kept at a distance
      of 10 mm from the bone surface. Additionally, histological analyses of the fresh
      osteotomy rims of lasered bone were performed. RESULTS: Er:YAG laser osteotomy
      revealed a remarkable cutting efficiency without any visible, negative, thermal
      side effects. There was no damage of adjacent soft tissue structures. However,
      depth control was limited to visual inspection. Histologically, a 5- to 10-microm
      wide zone of a characteristic laser fingerprint appeared on the cut edges.
      However, there was no sign of thermal tissue damage to the underlying bone
      structures. CONCLUSIONS: VSP Er:YAG laser osteotomy is clinically practicable
      without any signs of charred tissue and wound healing disturbances. However, the
      lack of depth control and the necessity for careful handling are still technical
      limitations to be overcome.

PMID- 19176968
TI  - Inhibition of hemoxygenase-1 improves survival after liver resection in jaundiced
      rats.
AB  - BACKGROUND: The role of hemoxygenase (HO)-1 after partial liver resection (PLR)
      in jaundiced animals has yet to be defined. We therefore investigated: (1) the
      acute effects of bile duct ligation (BDL) on bilirubin accumulation and
      hepatocellular integrity after PLR; (2) how BDL and PLR affect HO-1 protein
      expression; (3) how functional HO-1 blockade affects survival and liver
      regeneration after BDL and PLR. METHODS: Male Sprague-Dawley rats were subjected
      to BDL or a sham operation. After 3 days, a 70% hepatectomy was performed. In a
      second set of experiments, BDL animals received either Sn(IV) mesoporphyrin IX
      dichloride (SnMP) for HO-1 blockade or a vehicle. Three days later, PLR was
      performed and survival of the animals was observed for 7 days. RESULTS: PLR, BDL
      and both together cause a hepatocellular injury and HO-1 expression. Inhibition
      of HO-1 with SnMP in jaundiced rats that underwent PLR was associated with
      improved survival, attenuated postoperative weight loss and better liver
      synthesis. CONCLUSION: The present findings add further evidence that the
      protective properties of increased HO-1 expression largely depend on the model
      used, and that HO-1 overexpression in the model of liver resection during acute
      cholestasis may also be detrimental.

PMID- 19176969
TI  - Intrathoracic displacement of pleuroamniotic shunt after successful in utero
      treatment of fetal hydrops secondary to hydrothorax. Case report and review of
      the literature.
AB  - BACKGROUND: Primary fetal pleural effusion can be associated with high perinatal
      morbidity and mortality, especially when it is associated with the presence of
      fetal hydrops. Pleuroamniotic shunting results in effective drainage and lung
      expansion which prolong the pregnancy and improve neonatal survival.
      Intrathoracic displacement of the shunt is a rare but a known complication of
      shunt insertion and can cause some infant morbidity. We present a case of
      successful antenatal treatment of primary fetal pleural effusion complicated with
      intrathoracic displacement of the shunt without any fetal and long-term infant
      morbidity. CASE REPORT: Our case presented with severe bilateral fetal pleural
      effusion, causing fetal hydrops treated successfully by pleuroamniotic shunting
      at 25 weeks of gestation which was complicated by dislodgement of the shunt into
      the fetal chest documented by antenatal ultrasound at 30 weeks. There was no
      recurrence of fetal pleural effusion or other antenatal complication. After
      delivery there were no postnatal complications, so removal of the shunt was not
      considered, and clinical follow-up of the infant to the age of 12 months was
      uneventful. CONCLUSION: The complication of intrathoracic displacement of a
      pleuroamniotic shunt can be recognized antenatally by ultrasound. Since there are
      no postnatal pulmonary complications related to the presence of the shunt inside
      the infant chest, conservative management in these cases appears to be a safe
      approach.

PMID- 19176970
TI  - Prenatal diagnosis of fetal cardiac right ventricular diverticulum disappearing
      at three months of age. A case report and literature review.
AB  - Congenital cardiac diverticula are transmural localized protrusions within the
      free wall of the ventricles. Right ventricular diverticula are rarely diagnosed
      during the fetal period, and due to their rarity, their natural history remains
      unclear. We present a case of prenatal diagnosis of right ventricular
      diverticulum at 22 weeks' gestation. No other pathological findings were
      detected, the pregnancy and delivery were uneventful, and the diverticulum
      disappeared before the age of 3 months. Echocardiography of the infant at 1 year
      of age revealed no cardiac diverticulum or any cardiac anomaly and showed normal
      heart function. Literature review of all cases published to date reveal good
      outcome of right ventricular diverticula. We suggest reassuring our patients
      about the good prognosis of this cardiac anomaly.

PMID- 19176971
TI  - Prenatal cardiac ultrasound finding in congenital disorder of glycosylation type
      1a.
AB  - We present the antenatal cardiac findings in an infant in whom a postnatal
      diagnosis of congenital disorder of glycosylation type Ia (CDG-Ia) was confirmed.
      The antenatal findings at 34 weeks' gestation included biventricular cardiac
      hypertrophy with pericardial effusion, multiple skeletal anomalies and cerebral
      ventricular dilatation. A severe CDG-Ia multisystem clinical phenotype evolved in
      the postnatal period, with the infant succumbing at 3.5 weeks of age secondary to
      a large pericardial effusion with tamponade. A literature review suggests that
      this is the first case of cardiac manifestations of CDG-Ia observed antenatally.
      We would also like to suggest that CDG-Ia should be considered and if possible
      prenatal diagnosis performed in cases with hypertrophic cardiomyopathy, and/or
      pericardial effusion.

PMID- 19176972
TI  - Salivary gland homogenates of Lutzomyia longipalpis and its vasodilatory peptide
      maxadilan cause plasma leakage via PAC1 receptor activation.
AB  - OBJECTIVES: Experiments were designed to determine if salivary gland homogenates
      (SGH) of the sand fly Lutzomyia longipalpis, the vasodilatory peptides maxadilan
      and pituitary adenylate cyclase-activating peptide (PACAP-38) may cause plasma
      leakage and to what extent these effects could be due to PAC1 receptor
      stimulation. METHODS: Using FITC-dextran as a plasma marker, intravital
      microscopy of the hamster cheek pouch (HCP) and a digital camera were used to
      assess arteriolar diameter and fluorescence of a selected area (5 mm(2))
      representative of the HCP microcirculation. RESULTS: Cheek pouches prepared for
      intravital microscopy and exposed to topical application of SGH, maxadilan or
      PACAP-38 developed maximal dilation of arterioles in the range of 20-60 mum
      within 10 min, and this effect lasted for 30-90 min. The increase in fluorescence
      intensity induced by each of these compounds was due to plasma leakage from
      postcapillary venules. The mutant peptide of maxadilan (M-65), a PAC1 receptor
      antagonist, inhibited both dilation and plasma leakage induced by SGH or
      maxadilan. Plasma leakage induced by SGH was modestly inhibited by the bradykinin
      B(2) receptor antagonist HOE-140, but not by the antihistamine mepyramine or the
      nitric oxide synthase inhibitor L-NA. CONCLUSIONS: SGH of L. longipalpis and its
      vasodilatory peptide maxadilan caused long-lasting arteriolar dilation and plasma
      leakage in the cheek pouch via PAC1 receptor activation.

PMID- 19176973
TI  - Renal artery stenosis and renal parenchymal damage in patients with abdominal
      aortic aneurysm proven by autopsy.
AB  - BACKGROUND: Chronic kidney disease is a major risk factor for patients with
      cardiovascular diseases (CVD). The aim of this study is to evaluate the
      relationship between clinical characteristics and renal histology in patients
      with abdominal aortic aneurysm (AAA). METHODS: We studied 79 cases with AAA
      autopsied at the National Cardiovascular Center. They were classified into two
      groups: 14 subjects with renal artery stenosis (RAS) (group A) and 65 subjects
      without RAS (group B). Proteinuria, elevated serum creatinine and decreased
      estimated glomerular filtration rate had been recorded. We evaluated renal
      parenchymal damage using a semiquantitative histological score (score 0-3; normal
      to severe) for glomerulosclerosis, interstitial fibrosis, tubular atrophy, and
      arteriolar hyalinosis (maximal score = 12). RESULTS: Total histological score was
      8.2 +/- 2.4 and significantly higher in the stenosed kidneys of group A than in
      the non-stenosed kidneys of group B (8.9 +/- 2.6 vs. 8.0 +/- 2.3). The
      histological score had a significant association with RAS, smoking, kidney
      function, proteinuria, kidney weight and the presence of other CVD. CONCLUSION:
      We demonstrated that renal parenchymal damage and deteriorated kidney function
      are closely associated in the patients with AAA. Treatment of these patients in
      view of protection of the kidney is thus relevant.

PMID- 19176974
TI  - Adjustment for selection bias in observational studies with application to the
      analysis of autopsy data.
AB  - BACKGROUND: The interpretation of neuropathological studies of dementia and
      Alzheimer's disease is complicated by potential selection mechanisms that can
      drive whether or not a study participant is observed to undergo autopsy.
      Notwithstanding this, there appears to have been little emphasis placed on
      potential selection bias in published reports from population-based
      neuropathological studies of dementia. METHODS: We provide an overview of
      methodological issues relating to the identification of and adjustment for
      selection bias. When information is available on factors that govern selection,
      inverse-probability weighting provides an analytic approach to adjust for
      selection bias. The weights help alleviate bias by serving to bridge differences
      between the population from which the observed data may be viewed as a
      representative sample and the target population, identified as being of
      scientific interest. RESULTS: We illustrate the methods with data obtained from
      the Adult Changes in Thought study. Adjustment for potential selection bias
      yields substantially strengthened association between neuropathological
      measurements and risk of dementia. CONCLUSIONS: Armed with analytic techniques to
      adjust for selection bias and to ensure generalizability of results from
      population-based neuropathological studies, researchers should consider
      incorporating information related to selection into their data collection
      schemes.

PMID- 19176975
TI  - Selection bias. Importance of identification and adjustment.

PMID- 19176976
TI  - Neuroendocrinologies membership of the Neuroscience Peer Review Consortium.

PMID- 19176977
TI  - The Groningen Protocol - the Jewish perspective.
AB  - Despite significant advances in neonatology, there will always be newborns with
      serious life-threatening conditions creating most difficult bioethical dilemmas.
      Active euthanasia for adult patients is one of the most controversial bioethical
      questions; for severely ill neonates, the issue is even more complex, due to
      their inability to take part in any decision concerning their future. The
      Groningen Protocol introduced in 2005 by P.J. Sauer proposes criteria allowing
      active euthanasia for severely ill, not necessarily terminal, newborns with
      incurable conditions and poor quality of life in order to spare them unbearable
      suffering. We discuss the ethical dilemma and ideological foundations of the
      protocol, the opinions of its defenders and critics, and the dangers involved.
      The Jewish perspective relating to the subject is presented based on classical
      Jewish sources, which we trust may enrich modern bioethical debates. In Jewish
      law, the fetus acquires full legal status only after birth. However, while the
      lives of terminally ill neonates must in no way be actively destroyed or
      shortened, there is no obligation to make extraordinary efforts to prolong their
      lives. Accurate preimplantation or prenatal diagnosis might significantly reduce
      the incidence of nonviable births, but active killing of infants violates the
      basic foundations of Jewish law, and opens the 'slippery slope' for uncontrolled
      abuse. Therefore, we call upon the international medical and bioethical community
      to reject the Groningen Protocol that permits euthanization and to develop
      ethical guidelines for the optimal care of severely compromised neonates.

PMID- 19176978
TI  - The Groningen Protocol, unfortunately misunderstood. Commentary on Gesundheit et
      al.: The Groningen Protocol - the Jewish perspective (neonatology 2009;96:6-10).

PMID- 19176979
TI  - Differential and synergistic effect of nerve growth factor and cAMP on the
      regulation of early response genes during neuronal differentiation.
AB  - Neurotrophin (NT)-driven differentiation is a process involving activation of
      multiple signalling events. Treatment of PC12 cells with the prototypic NT nerve
      growth factor (NGF) induces PC12 cell differentiation characterized by neurite
      outgrowth and expression of differentiation genes. Cyclic AMP (cAMP), one of the
      second messengers of NGF stimulation, has also been observed to induce neuronal
      differentiation in PC12 cells. Interestingly, co-treatment of NGF and dibutyryl
      cAMP (DBcAMP) exhibits a synergistic effect on neurite outgrowth in PC12 cells,
      but the mechanisms underlying this synergism remain unknown. In the current
      study, we compared the gene expression profiles of PC12 cells treated with NGF,
      DBcAMP or both for 12 h to identify differentially regulated genes during the
      early stage of differentiation. We found that the genes that were differentially
      regulated by NGF, DBcAMP or both include genes for acquiring neuronal phenotypes,
      cytoskeleton-binding proteins and cell cycle proteins. Importantly, we identified
      a subset of genes that was specifically regulated during co-treatment of NGF and
      cAMP, suggesting that the synergistic effect of NGF and DBcAMP on neurite
      outgrowth is possibly mediated through transcription regulation. Our observations
      provide novel insights on the signalling mechanisms underlying the regulation of
      neuronal differentiation by NGF and cAMP.

PMID- 19176980
TI  - Diminished presynaptic GABA(B) receptor function in the neocortex of a genetic
      model of absence epilepsy.
AB  - Changes in GABA(B) receptor subunit expression have been recently reported in the
      neocortex of epileptic WAG/Rij rats that are genetically prone to experience
      absence seizures. These alterations may lead to hyperexcitability by
      downregulating the function of presynaptic GABA(B) receptors in neocortical
      networks as suggested by a reduction in paired-pulse depression. Here, we tested
      further this hypothesis by analyzing the effects induced by the GABA(B) receptor
      agonist baclofen (0.1-10 microM) on the inhibitory events recorded in vitro from
      neocortical slices obtained from epileptic (>180 day-old) WAG/Rij and age
      matched, non-epileptic control (NEC) rats. We found that higher doses of baclofen
      were required to depress pharmacologically isolated, stimulus-induced IPSPs
      generated by WAG/Rij neurons as compared to NEC. We also obtained similar
      evidence by comparing the effects of baclofen on the rate of occurrence of
      synchronous GABAergic events recorded by WAG/Rij and NEC neocortical slices
      treated with 4-aminopyridine + glutamatergic receptor antagonists. In conclusion,
      these data highlight a decreased function of presynaptic GABA(B) receptors in the
      WAG/Rij rat neocortex. We propose that this alteration may contribute to
      neocortical hyperexcitability and thus to absence seizures.

PMID- 19176982
TI  - Evaluation of the antidiabetic effects of dipeptidyl peptidase-IV inhibitor
      ASP8497 in streptozotocin-nicotinamide-induced mildly diabetic mice.
AB  - Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) has a potent glucose
      dependent insulinotropic effect and is rapidly degraded by dipeptidyl peptidase
      (DPP)-IV. Therefore, the use of DPP-IV inhibitors is being actively explored as a
      novel approach to the treatment of type 2 diabetes. The present study
      investigated the antidiabetic effects of the DPP-IV inhibitor ASP8497 in
      streptozotocin-nicotinamide-induced mildly diabetic mice which possess
      aggravation of glucose tolerance due to loss of early-phase insulin secretion.
      ASP8497 exhibited good oral bioavailability with potent inhibition of plasma DPP
      IV activity. This inhibitory activity lasted up to 24 h when administered at 5
      mg/kg twice a day or 10 mg/kg once a day. A single oral administration of ASP8497
      (0.3-3 mg/kg) significantly improved glucose tolerance by increasing plasma
      insulin and GLP-1 levels during the oral glucose or liquid meal tolerance tests.
      These effects were seen not only immediately, but also 8 h after administration.
      In contrast, ASP8497 (0.3-10 mg/kg) had no significant effect on blood glucose
      and plasma insulin levels under fasting conditions. Furthermore, repeated
      administration of ASP8497 (5 mg/kg twice a day or 10 mg/kg once a day) for 25
      days significantly decreased nonfasting blood glucose and HbA(1c) levels. These
      results suggest that ASP8497 is a potent and long-acting DPP-IV inhibitor that
      improves glucose tolerance through glucose-dependent insulinotropic action via
      the elevation of the GLP-1 level in streptozotocin-nicotinamide-induced mildly
      diabetic mice. It is expected to be useful as a therapeutic agent for impaired
      glucose tolerance and type 2 diabetes.

PMID- 19176981
TI  - Bipolar radiofrequency uvulopalatoplasty combined with injection snoreplasty: a
      reasonable option for the problem of snoring.
AB  - OBJECTIVES: The aim of this study was to assess the effectiveness and morbidity
      of the combined use of bipolar radiofrequency uvulopalatoplasty and a sclerosing
      agent applied to the soft palate in patients with snoring and apnea during a 1
      year follow-up period. METHODS: This was a prospective, nonrandomized study.
      Twenty-eight patients with primary snoring due to palatal flutter who fulfilled
      the inclusion criteria were enrolled. Under local anesthesia, a single procedure
      uvulopalatoplasty using bipolar radiofrequency applied with sterilized forceps
      was undertaken in combination with a sclerosing agent. RESULTS: Four patients
      required a repeat procedure 6 weeks after the initial operation. The
      postoperative Epworth Sleepiness Scale score improved significantly 360 days
      after surgery. Snoring, measured on the Visual Analogue Scale, decreased from 8.9
      +/- 0.7 to 4.1 +/- 1.4 (p < 0.005). No complications were reported. The average
      reduction on the apnea-hypopnea index was from 24.2 +/- 7.1 to 12.8 +/- 4.4 (p <
      0.005). CONCLUSION: Bipolar radiofrequency uvulopalatoplasty combined with
      injection snoreplasty is an ambulatory, cost-effective, simple, and safe method
      to reduce the occurrence and effects of snoring and apnea.

PMID- 19176983
TI  - Effects of the phosphodiesterase type 4 inhibitor roflumilast on early and late
      allergic response and airway hyperresponsiveness in Aspergillus-fumigatus
      sensitized mice.
AB  - BACKGROUND: Inhibitory effects of roflumilast on responses characteristic of
      allergic asthma were investigated in a fungal asthma model in BALB/c mice.
      METHODS: Mice were sensitized with Aspergillus antigen (Afu) and exposed to Afu
      or vehicle, and given roflumilast 1 or 5 mg/kg. Early airway response (EAR) and
      late airway hyperresponsiveness (AHR) to methacholine were measured via
      plethysmography. Bronchoalveolar lavage (BAL) was used to assess inflammatory
      cell count. RESULTS: In Afu-exposed mice, roflumilast dose-dependently reduced
      the EAR [26% at 1 mg/kg (NS) and 94% at 5 mg/kg (p < 0.01)] and AHR [46% at 1
      mg/kg (NS) and 128% at 5 mg/kg (p < 0.05)]. Roflumilast 5 mg/kg reduced
      neutrophil, eosinophil and lymphocyte counts [87% (p < 0.01), 40% (NS) and 67% (p
      < 0.01), respectively] in BAL fluid versus controls. CONCLUSIONS: In this model,
      roflumilast inhibited the EAR, suppressed AHR and reduced inflammatory cell
      infiltration.

PMID- 19176984
TI  - Blood coagulation and cancer: thrombosis and survival, clinical relevance and
      impact. An introduction.
AB  - There is a strong association between deep venous thrombosis and cancer. In this
      review, we will discuss the increased incidence of cancer following an idiopathic
      venous thrombotic event (VTE) and the increased incidence of VTE and its
      recurrence in cancer patients. Furthermore, we will review the adverse impact VTE
      has on cancer patients' morbidity and mortality. Finally, the potential influence
      of anticoagulation on survival of cancer patients is discussed. Although the data
      are encouraging, anticoagulation is still of limited value for routine clinical
      practice in anticancer treatment.

PMID- 19176985
TI  - Overview of the postulated mechanisms linking cancer and thrombosis.
AB  - Blood coagulation appears to play an important role in the occurrence of cancer
      and its effects may be twofold. First, in patients with cancer, blood coagulation
      is activated in the direction of a prothrombotic state. Second, a procoagulant
      environment may promote cancer in different ways. In this chapter we discuss some
      of the mechanisms that may be involved in this interplay between coagulation and
      cancer. Blood coagulation proteins interact with cells in the vasculature to
      maintain hemostasis. However, many proteins that are involved in coagulation and
      anticoagulation, as well as fibrinolysis, are also found in extravascular
      tissues. In different organs, these proteins may be involved in cell-signaling
      mechanisms, through interaction with cell receptors like protease-activated
      receptors (PARs). Such interactions may drive inflammation, angiogenesis and cell
      proliferation. The potential procarcinogenic actions of proteases like thrombin
      may be counteracted by the anticoagulant and anti-inflammatory actions of the
      protein C-thrombomodulin mechanism. In the blood of cancer patients, the balance
      is usually shifted towards a procoagulant direction. The resulting excess
      thrombin- and fibrin-forming activity promotes venous thrombosis and may in the
      extravascular compartment stimulate cancer progression. The activation of
      platelets and their interaction with leukocytes may propagate this process. In
      addition to the therapeutic modulation of the prothrombotic environment, the
      induction of specific anticoagulant proteins including thrombomodulin may have
      effects on tumor growth or dissemination, but the nature of these effects still
      remains hard to predict. The interplay between cancer and blood coagulation
      merits further experimental and clinical research.

PMID- 19176986
TI  - Thrombophilia and cancer.
AB  - Inherited and acquired thrombophilia are well-known risk factors for venous
      thromboembolism. The incidence of thrombotic events in cancer patients is
      increased compared to normal population. Data on inherited thrombophilia and
      cancer is limited. Most studies are small, and results are varied by geography,
      tumor type, stage of disease and therapy. Nevertheless, it seems that factor V
      Leiden and prothrombin mutation may increase VTE risk in cancer patients. Data
      also exist for hyperhomocysteinemia. Cancer patients with thrombophilia who have
      a central vein catheter are a special group with increased venous thrombotic
      event (VTE) risk. Among acquired risk factors, antiphospholipid antibodies are
      common in cancer patients, especially in lymphoproliferative diseases. Published
      data suggests that the risk of thrombotic events, venous and arterial, is
      increased in cancer patients with antiphospholipid antibodies. The questions of
      screening cancer patients for inherited thrombophilia or antiphospholipid
      antibodies are unclear. There is no data on primary VTE prophylaxis in cancer
      patients with thrombophilia and prophylaxis for cancer patients with central vein
      catheters is controversial.

PMID- 19176987
TI  - Protease-activated receptors, apoptosis and tumor growth.
AB  - Protease-activated receptors (PARs) are G-protein-coupled receptors (GPCRs) that
      are activated by a unique proteolytic mechanism. Besides the important role of
      blood coagulation factors in preventing bleeding after vascular injury, these
      serine proteinases actively engage target cells thereby fulfilling critical
      functions in cell biology. Cellular responses triggered by coagulation factor
      induced PAR activation suggest that PARs play an important role in proliferation,
      survival and/or malignant transformation of tumor cells. Indeed, PAR expression
      correlates with cancer malignancy and clinical studies show that anticoagulant
      treatment is beneficial in cancer patients. In this review, we provide an
      overview on the PAR family, their mode of activation and mechanisms by which PAR
      signaling is terminated. In addition, we discuss the relationship between blood
      coagulation and cancer biology focusing on the potential role of PAR-induced
      modulation of cell survival, apoptosis and tumor growth.

PMID- 19176988
TI  - Leukocytosis, JAK2V617F mutation, and hemostasis in myeloproliferative disorders.
AB  - Thrombosis is a leading cause of morbidity and mortality in patients with
      essential thrombocythemia (ET) and polycythemia vera (PV). Several mechanisms
      have been proposed to cause or to contribute to the acquired thrombophilic state
      of these patients, including platelet and red blood cell abnormalities. The
      increase in white blood cell count, found in most subjects with these disorders,
      raises the possibility that circulating leukocytes may represent another
      prothrombotic factor, as demonstrated for other conditions, including sickle
      cell, coronary heart, and peripheral arterial diseases. Published data
      demonstrate that neutrophil activation occurs in ET and PV patients in parallel
      with the appearance of laboratory signs of hemostatic system activation,
      suggesting an involvement of these cells in the pathogenesis of the thrombotic
      predisposition of these subjects. In 2005, an acquired point mutation in the
      pseudokinase domain of Janus kinase 2 (JAK2(V617F)) has been described in these
      disorders, and has attracted an enormous interest both as a diagnostic and
      prognostic tool, and as a potential therapeutic target. Retrospective data have
      identified JAK2(V617F) as a risk factor for thrombosis in ET, and have also shown
      a close association with abdominal vein thrombosis. JAK2(V617F) is variably
      associated with thrombosis and, more consistently, with elevations in blood cell
      counts. A clear link appears to exist between leukocytosis, JAK2(V617F), and the
      hemostatic system activation in patients with Bcl-negative myeloproliferative
      disorders.

PMID- 19176989
TI  - Tissue factor and cancer.
AB  - Tissue factor (TF), the key regulator of haemostasis and angiogenesis, is also
      involved in the pathology of several diseases, including cardiovascular,
      inflammatory and neoplastic conditions. In the latter, TF is upregulated by
      cancer cells, as well as by certain host cells, and it is the interactions
      between these distinct pools of TF-expressing cells that likely influence tumour
      progression in several ways. Furthermore, the release of TF microparticles into
      the circulation is thought to contribute to the systemic coagulopathies commonly
      observed in cancer patients. The direct regulation of TF by oncogenic events has
      provided a plausible explanation for the relatively common overexpression of TF
      in various cancers and its involvement in tumour growth, angiogenesis, metastasis
      and coagulopathy. However, this constitutive influence is modified by the tumour
      microenvironment, cellular interactions and host factors rendering TF expression
      patterns complex and heterogeneous. It appears that in many biological contexts
      TF plays a central role in disease progression and thereby potentially
      constitutes an attractive therapeutic target, especially in scenarios where the
      risk of bleeding can be avoided by selecting appropriate medications, refined
      dosing or by targeting the signalling component of TF activity. The efficacy and
      safety of such approaches still awaits clinical verification.

PMID- 19176990
TI  - Microparticles and cancer.
AB  - Cancer is a prothrombotic state, with an increased prevalence of arterial and
      venous thromboemboli. Microparticles (MPs) are sub-micron-sized vesicles derived
      from activated or apoptotic cancer cells and/or host cells that may causally
      contribute to these clinical events, although the strength of the evidence thus
      far is inconclusive. We review the state-of-the-art understanding of the origin
      of circulating MPs, their role as a potentially important procoagulant entity in
      cancer, and their clinically documented association with malignancies. It is
      anticipated that if the functional importance of circulating MPs in clinically
      meaningful endpoints in cancer can be proven by appropriately designed and
      powered prospective studies, future investigation will focus on whether MPs can
      be targeted for therapeutic purposes.

PMID- 19176991
TI  - The plasminogen activator system and cancer.
AB  - The fibrinolytic system, more appropriately referred to as the plasminogen
      activator system, controls not only the intravascular fibrin deposition but also
      participates in a wide variety of physiologic and pathologic processes. In
      cancer, the components of this system are involved in tumor growth, invasion and
      metastasis, through their effect on angiogenesis and cell migration. These
      components are found in most tumors and their expression signifies not only their
      function but also carries a prognostic value. Their expression is in turn
      modulated by cytokines and growth factors, many of which are up-regulated in
      cancer. Though both plasminogen activators, tPA and uPA, are expressed in tumor
      cells, uPA with its receptor (uPAR) is mostly involved in cellular functions,
      while tPA with its receptor annexin II on endothelial surface regulates
      intravascular fibrin deposition. Among the inhibitors of fibrinolysis, PAI-1 is a
      major player in the pathogenesis of many vascular diseases as well as in cancer.
      Therapeutic intervention, either using plasminogen activators or use of
      experimental inhibitor agents against PAI-1, has shown encouraging results in
      experimental tumors but not verified clinically. Information provided in this
      brief review is aimed to promote greater interest in the role of the plasminogen
      activator system in cancer.

PMID- 19176993
TI  - Clinical studies with anticoagulants to improve survival in cancer patients.
AB  - Cancer is linked with hypercoagulability and risk of thrombosis and this close
      association was recognized by Armand Trousseau in 1865. The relation between
      cancer and blood coagulation is reciprocal: cancer induces a hypercoagulable
      state and predisposes to thrombosis and activation of platelets, blood
      coagulation and fibrinolysis interfere with tumor cell biology, tumor growth,
      angiogenesis and metastatic process. In the present article, we analyze the
      clinical trials which assessed the influence of anticoagulant treatment on the
      survival of patients with cancer. The available data show that low-molecular
      weight heparins (LMWHs) tend to be more effective and safer than vitamin K
      antagonists (VKA) in improving survival in patients with cancer. The beneficial
      effect of anticoagulation with either LMWHs or VKA is not universal for all
      patients with cancer. There are some histological types of cancers which, at
      early stages, appear to be more sensitive than others to the effect of
      anticoagulant treatment. The available clinical trials, although limited, are
      encouraging for the beneficial effect of anticoagulant treatment on the survival
      of cancer patients. More clinical trials are needed, targeting groups of patients
      homogenous regarding the type of cancer, the stage of the disease and life
      expectancy. The forthcoming clinical trials have to address some issues regarding
      the optimal dose, the timing and the duration of treatment with LMWH in relation
      to chemotherapy or other anticancer therapies.

PMID- 19176994
TI  - The pathophysiology of cancer and thrombosis. Summary and conclusions.

PMID- 19176992
TI  - Non-anticoagulant heparins and inhibition of cancer.
AB  - Low-molecular-weight heparins (LMWH) appear to prolong survival of patients with
      cancer. Such a beneficial effect is thought to be associated with interruption of
      molecular mechanisms involving the heparan sulfate (HS) chains of cell surface
      and extracellular matrix proteoglycans (HSPGs), growth factors and their
      receptors, heparanase, and selectins. The beneficial effects of heparin species
      could also be associated with their ability to release tissue factor pathway
      inhibitor from endothelium. The utility of heparin and LMWH as anticancer drugs
      is limited due to their anticoagulant properties. Non-anticoagulant heparins can
      be obtained either by removing chains containing the antithrombin-binding
      sequence, or by inactivating critical functional groups or units of this
      sequence. The non-anticoagulant heparins most extensively studied are
      regioselectively desulfated heparins and 'glycol-split' heparins. Some modified
      heparins of both types are potent inhibitors of heparanase. A number of them also
      attenuate metastasis in experimental models. With cancer cells overexpressing
      selectins, heparin-mediated inhibition of tumor cells-platelets aggregation and
      tumor cell interaction with the vascular endothelium appears to be the prevalent
      mechanism of attenuation of early stages of metastasis. The structural
      requirements for inhibition of growth factors, heparanase, and selectins by
      heparin derivatives are somewhat different for the different activities. An N
      acetylated, glycol-split heparin provides an example of application of a non
      anticoagulant heparin that inhibits cancer in animal models without unwanted side
      effects. Delivery of this compound to mice bearing established myeloma tumors
      dramatically blocked tumor growth and progression.

PMID- 19176995
TI  - Starting with a look into the face.

PMID- 19176996
TI  - Mitotic crisis: the unmasking of a novel role for RPA.
AB  - Mitotic DNA damage is a constant threat to genomic integrity, yet understanding
      of the cellular responses to this stress remain incomplete. Recent work by
      Anantha et al. (2008; PNAS 105:12903-8) has found surprising evidence that RPA,
      the primary eukaryotic single-stranded DNA-binding protein, can stimulate the
      ability of cells to exit mitosis into a 2N G(1) phase. Along with providing
      additional discussion of this study, we review evidence suggesting that DNA
      replication and repair factors can modulate mitotic transit by acting through
      Polo-like kinase-1 (Plk1) and the centrosome. 'A crisis unmasks everyone.'-Mason
      Cooley, U.S. aphorist.

PMID- 19176997
TI  - Does the cell number 10(9) still really fit one gram of tumor tissue?
AB  - A tumor reaching the size of 1 cm(3) (approximately 1 g wet weight) is commonly
      assumed to contain 1 x 10(9) cells. This paper comments on the probable origin of
      this "magic" number and on some possible reasons why it has remained in use until
      now. However, mostly in epithelial tumors (85% of all human tumors) a cell number
      one order of magnitude smaller would be more realistic.

PMID- 19176998
TI  - Mdm2 and PCAF increase Chk2 ubiquitination and degradation independently of their
      intrinsic E3 ligase activities.
AB  - We have previously shown that Chk2 stability, which is increased after DNA damage
      in some cells, is regulated in part through phosphorylation at S456 and that a
      mutant Chk2 (S456A) is hyperubiquitinated and turned over more rapidly than wild
      type Chk2.(1) Here we show that the S456A mutant preferentially binds to Mdm2
      compared to wild-type Chk2 and downregulation of Mdm2 with siRNA can rescue the
      observed destabilization of S456A Chk2 following DNA damage. Ubiquitination of
      wild-type Chk2 is increased by co-expression of Mdm2, and increasing amounts of
      Mdm2 enhance degradation of both wild-type and mutant S456A Chk2. Surprisingly,
      however, an E3 ligase defective version of Mdm2 (DeltaC7) also increases
      ubiquitination and degradation of Chk2 when transfected into cells, suggesting
      that the ability of Mdm2 to affect Chk2 turnover is independent of its intrinsic
      E3 ligase function. Recently the acetyltransferase PCAF was shown to have
      intrinsic E3 ligase activity against itself and Mdm2. We found that PCAF
      interacts with both Mdm2 and Chk2 and that PCAF increases Chk2 ubiquitination and
      degradation. Interestingly as well, a PCAF deletion mutant that lacks E3 ligase
      activity towards Mdm2 also enhances Chk2 degradation. We hypothesize that Mdm2
      and PCAF may function as part of a multi-subunit E3 complex in their regulation
      of Chk2 turnover.

PMID- 19176999
TI  - The miR-302-367 cluster as a potential stemness regulator in ESCs.
AB  - Increasing experimental evidence suggests an important role of miRNAs in
      embryonic stem cell (ESC) biology. The miR-302-367 cluster is exclusively
      expressed at high levels in ESCs but not in either somatic stem cells or
      adult/embryonic differentiated cells. The human miR-302-367 gene structure has
      been recently described and its promoter has been identified, characterized and
      functionally validated in human stem cells. The miR-302-367 promoter activity
      depends on the ontogeny and hierarchical cellular stage. The miR-302-367 promoter
      is transcriptionally regulated by the ESC-specific transcription factors Oct3/4,
      Sox2 and Nanog and, its activity restricted to the ESC compartment. Functionally,
      this cluster regulates cell cycle in ESCs promoting self-renewal and
      pluripotency, therefore representing a master regulator in the maintenance of
      hESC stemness. We envision this data may open up new avenues to investigate the
      transcriptional regulators upstream miR-302-367 cluster and to dissect the
      complex interplay by which this miR-302-367 cluster integrates in the molecular
      network conferring pluripotency to ESCs. In this perspective, we summarize recent
      progress in the genomic and functional characterization of the miR-302-367
      cluster and discuss its potential as a stemness determinant.

PMID- 19177002
TI  - Molecular pharmacology of phosphatidylinositol 3-kinase inhibition in human
      glioma.
AB  - Gliomas are primary brain tumors with poor prognosis that exhibit frequent
      abnormalities in phosphatidylinositol 3-kinase (PI3 kinase) signaling. We
      investigated the molecular mechanism of action of the isoform-selective class I
      PI3 kinase and mTOR inhibitor PI-103 in human glioma cells. The potent inhibitory
      effects of PI-103 on the PI3 kinase pathway were quantified. PI-103 and the mTOR
      inhibitor rapamycin both inhibited ribosomal protein S6 phosphorylation but there
      were clear differences in the response of upstream components of the PI3 kinase
      pathway, such as phosphorylation of Thr(308)-AKT, that were inhibited by PI-103
      but not rapamycin. Gene expression profiling identified altered expression of
      genes encoding regulators of the cell cycle and cholesterol metabolism, and genes
      modulated by insulin or IGF1 signaling, rapamycin treatment or nutrient
      starvation. PI-103 decreased expression of positive regulators of G(1)/S phase
      progression and increased expression of the negative cell cycle regulator
      p27(kip1). A reversible PI-103-mediated G(1) cell cycle arrest occurred without
      significant apoptosis, consistent with the altered gene expression detected. PI
      103 induced vacuolation and processing of LC-3i to LC-3ii, which are features of
      an autophagic response. In contrast to PI-103, LY294002 and PI-387 induced
      apoptosis, indicative of likely off-target effects. PI-103 interacted
      synergistically or additively with cytotoxic agents used in the treatment of
      glioma, namely vincristine, BCNU and temozolomide. Compared to individual
      treatments, the combination of PI-103 with temozolomide significantly improved
      the response of U87MG human glioma xenografts. Our results support the
      therapeutic potential for PI3 kinase inhibitors with a PI-103-like profile as
      therapeutic agents for the treatment of glioma.

PMID- 19177000
TI  - The spindle assembly checkpoint in Caenorhabditis elegans: one who lacks Mad1
      becomes mad one.
AB  - The spindle assembly checkpoint (SAC) monitors the microtubule attachment status
      of the kinetochore and arrests cells before anaphase until all pairs of sister
      kinetochores achieve bipolar attachment of microtubules, thereby ensuring
      faithful chromosome transmission. The evolutionarily conserved coiled-coil
      protein MAD1 has been implicated in the SAC signaling pathway. MAD1 forms a
      complex with another SAC component MAD2 and specifically localizes to unattached
      kinetochores to facilitate efficient binding of MAD2 to its target, CDC20, the
      mitotic substrate-specific activator of the anaphase promoting complex or
      cyclosome (APC/C). Thus, MAD1 connects 2 sequential events in the SAC signaling
      pathway-recognition of unattached kinetochores and inhibition of APC/C activity.
      However, the molecular mechanisms by which it specifically localizes to
      unattached kinetochores are largely unknown. Studies in multicellular organisms
      have revealed the role of MAD1 in development and tumor suppression, but the
      precise time at which MAD1 activity is required is unknown. Investigation of
      cellular and organismic functions of MAD1 in the simple multicellular organism C.
      elegans identified functional interactors of MAD1 in both kinetochore-oriented
      SAC signaling and kinetochore-independent cell cycle regulation. Studying the
      function of SAC components in C. elegans provides a new molecular insight into
      the SAC-regulated cell cycle progression in a context of a multicellular
      organism.

PMID- 19177004
TI  - Long-term downregulation of Polo-like kinase 1 increases the cyclin-dependent
      kinase inhibitor p21(WAF1/CIP1).
AB  - Polo-like kinase 1 (Plk1) is overexpressed in tumor tissues and its expression
      level is tightly associated with the malignancy of tumors and prognosis of tumor
      patients. Thus, Plk1 is considered as one of the most attractive molecular
      targets for anticancer therapy. Recently, several small molecule inhibitors of
      Plk1 have been identified and characterized, and the first generation of Plk1
      inhibitors has been investigated in clinical trials. However, the long-term
      effect of the downregulation of Plk1 on tumor cells has not yet been studied. In
      this work we have investigated the phenotype of HeLa cells, in which Plk1 is
      continuously downregulated by constitutive expression of shRNA. The data
      demonstrate that the long-term suppression of Plk1 increases the levels of
      cyclindependent kinase inhibitor p21(WAF1/CIP), which is partially induced by the
      elevated tumor suppressor p73 in p53-inactivated HeLa cells. The increased kinase
      inhibitor p21(WAF1/CIP1) localizes in both cyctoplasm as well as in nucleus and
      interacts directly with Cdk1/cyclin B1. Moreover, the knockdown of Plk1 leads to
      a decreased oncoprotein MDM2 and an elevated pro-apoptotic protein Bax in HeLa
      cells. Importantly, HeLa cells with reduced level of Plk1, which induces an
      increase of p21, p73 and Bax, are more sensitive to some chemotherapeutic agents,
      such as cisplatin.

PMID- 19177006
TI  - RNA-binding motif protein 35A is a novel tumor suppressor for colorectal cancer.
AB  - The frequent occurrence of inactivating gene mutations in tumors suggests a tumor
      suppressor function of the mutated gene. The RNA binding motif protein 35A
      (RBM35A) is mutated in approximately 50% of analyzed primary colon tumors with
      microsatellite instability. The Tet-off regulated ectopic expression of RBM35A
      gene in RBM35A-null LS180 colon carcinoma cells inhibited anchorage-independent
      growth in vitro, suppressed tumorigenic potential in vivo and enhanced
      adhesiveness of these cancer cells. Using microarray hybridization we found that
      in response to RBM35A expression a small fraction of genes showed a decrease in
      polysome-associated mRNA. Experiments using cell-free in vitro translation system
      demonstrated that RBM35A differentially affects translation of luciferase
      reporter mediated by various 5'untranslated regions (UTR). We found that Gibbs
      energy value (DeltaG) of secondary structure formed by 5'UTRs of mRNAs can
      account for differential effect of RBM35A on reporter translation efficiency.
      Targeted mutation in the FOS 5'UTR sequence, which increased the DeltaG value of
      hairpin stem formation, resulted in a stronger inhibitory effect of RBM35A on
      reporter translation efficiency mediated by this UTR. Immunoblotting revealed
      that ectopic expression of RBM35A in LS180 cells caused alterations in protein
      levels for several cancer related genes. Our results demonstrate for the first
      time that RBM35A functions as a tumor suppressor in colon cancer cells. We
      propose that RBM35A is involved in posttranscriptional regulation of a number of
      genes by exerting a differential effect on protein translation via 5'UTRs of
      mRNAs.

PMID- 19177007
TI  - How epigenetics can explain human metastasis: a new role for microRNAs.
AB  - The metastatic process is characterized by the dissemination of tumoral cells
      throughout the bloodstream to distal sites, where these transformed cells
      proliferate and give rise to secondary tumors, which are the principal cause of
      mortality in cancer patients. In recent years, a significant number of metastasis
      related genes have been described, such as cadherins, laminins, heparan sulfates
      and protease and angiogenesis inhibitors, among others. However, the mechanisms
      by which these genes are altered in metastasis remain unclear, since genetic
      alterations occur rarely, despite their widespread downregulation. Epigenetic
      alterations, and specifically CpG island hypermethylation-associated silencing,
      can potentially explain the aberrant expression of many of these genes. The
      disruption of histone modifiers and chromatin-remodeling factors also contributes
      to the alteration of metastasis genes. Members of a new class of regulatory RNAs,
      microRNAs (miRNAs), have an important role in cancer and metastasis and are also
      regulated by epigenetic mechanisms in both malignancies. As we gain insight into
      the epigenetic mechanisms orchestrating all the metastatic steps, we broaden the
      therapeutic possibilities of epigenetic drugs, such as DNA demethylating drugs
      and histone deacetylase inhibitors, which can act upon metastasis-related genes
      and miRNAs, restoring their expression. In this review, the latest studies
      relating cancer epigenetics and metastasis are analyzed, and we emphasize the
      importance of miRNAs and their epigenetic regulation in tumoral progression.

PMID- 19177005
TI  - PI3K/mTORC1 activation in hamartoma syndromes: therapeutic prospects.
AB  - Dysregulated activity of phosphatidylinositol 3-kinase (PI3K) and mammalian
      target of rapamycin complex 1 (mTORC1) is characteristic feature of hamartoma
      syndromes. Hamartoma syndromes, dominantly inherited cancer predisposition
      disorders, affect multiple organs and are manifested by benign tumors consisting
      of various cell types native to the tissues in which they arise. In the past few
      years, three inherited hamartoma syndromes, Cowden syndrome (CS), tuberous
      sclerosis complex (TSC) syndrome, and Peutz-Jeghens syndrome (PJS), have all been
      linked to a common biochemical pathway: the hyperactivation of PI3K/mTORC1
      intracellular signaling. Three tumor suppressors, PTEN (phosphatases and tensin
      homolog), tuberous sclerosis complex TSC1/TSC2, and LKB1, are negative regulators
      of PI3K/mTORC1 signaling; disease-related inactivation of these tumor suppressors
      results in the development of PTEN-associated hamartoma syndromes, TSC and PJS,
      respectively. The goal of this review is to provide a roadmap for navigating the
      inherently complex regulation of PI3K/mTORC1 signaling while highlighting the
      progress that has been made in elucidating the cellular and molecular mechanisms
      of hamartoma syndromes and identificating potential therapeutic targets for their
      treatment. Importantly, because the PI3K/mTORC1 pathway is activated in the
      majority of common human cancers, the identification of novel molecular target(s)
      for the treatment of hamartoma syndromes may have a broader translational
      potential, and is critically important not only for therapeutic intervention in
      hamartoma disorders, but also for the treatment of cancers.

PMID- 19177008
TI  - In vivo measurement of signaling cascade dynamics.
AB  - Genetic and biochemical studies yield information about the component proteins
      and interactions involved in a cellular signaling pathway. However this parts
      inventory often does not immediately reveal the in vivo signal processing
      capabilities and function of the pathway. Signaling pathways are complex systems
      with dynamic behavior and a systems level approach is needed to understand the
      physiological roles they play within the cell. We recently used such an approach
      to measure the signal processing behavior of the budding yeast HOG MAP kinase
      pathway in response to precisely varied temporal stimuli controlled with a
      microfluidic device. Despite being a well-studied pathway with well-known
      components the signaling dynamics and biochemical parameters of this pathway were
      not known. Our approach allowed us to characterize the pathway's in vivo signal
      processing and put bounds on all of the in vivo reaction rates. The experimental
      and theoretical techniques used in our study are general and can be applied to
      understanding other signaling pathways in a range of biological systems.

PMID- 19177009
TI  - Subnuclear compartmentalization of transiently expressed polyadenylated pri
      microRNAs: processing at transcription sites or accumulation in SC35 foci.
AB  - MicroRNAs (miRNAs) are small, noncoding RNAs that post-transcriptionally regulate
      expression of their target messenger RNAs. We recently demonstrated that primary
      miRNA transcripts (pri-miRNAs) retained at transcription sites are processed with
      enhanced efficiency, suggesting that pri-miRNA processing is coupled to
      transcription in mammalian cells. We also observed that transiently expressed pri
      miRNAs accumulate in nuclear foci with splicing factor SC35 and Microprocessor
      components, Drosha and DGCR8. Here, we show that pri-miRNAs containing a self
      cleaving hepatitis delta ribozyme accumulate in the nucleoplasm after release
      from their transcription sites, but are not efficiently processed. Pri-miRNAs
      with ribozyme-generated 3' ends do not localize to SC35-containing foci, whereas
      cleaved and polyadenylated pri-miRNA transcripts with or without the pre-miRNA
      hairpin do. Pri-miRNA/SC35 foci contain a number of proteins normally associated
      with SC35 domains, including ASF/SF2, PABII, and the prolyl isomerase, Pin1. In
      contrast, RNA polymerase II and PM/Scl-100 do not strongly colocalize with pri
      miRNAs in SC35-containing foci. These data argue that pri-miRNA/SC35-containing
      foci are not major sites of pri-miRNA processing and that pri-miRNA processing is
      coupled to transcription. We discuss the implications of our findings relative to
      recent insights into miRNA biogenesis, mRNA metabolism, and the nuclear
      organization of gene expression.

PMID- 19177011
TI  - Ras alters epithelial-mesenchymal transition in response to TGFbeta by reducing
      actin fibers and cell-matrix adhesion.
AB  - TGF-beta and Ras regulate epithelial-mesenchymal transition (EMT), a process that
      contributes to tumor invasion and metastasis. The interaction of these pathways
      in EMT is still poorly understood. Here, we show that TGF-beta induces EMT but
      limits cell invasion whereas hyperactivated Ras (H-RasV12) does not cause EMT but
      enhances cell invasion, alleviating the inhibitory effect of TGF-beta. TGF-beta
      disrupts cell junctions and induces tropomyosin-mediated actin fibers and matrix
      adhesion. Smad transcription factors mediate both steps of the TGF-beta-induced
      EMT whereas RasV12 inhibits the second step by blocking the induction of
      tropomyosins (TPM1) and reducing cell-matrix adhesion and integrin signaling.
      RasV12 prevents binding of Smads to the TPM1 promoter by forcing CRM1-dependent
      nuclear export of Smad4. Soft agar and animal studies demonstrate that RasV12
      confers the metastatic potential in epithelial cells, whereas tropomyosin
      suppresses tumor growth and metastases. Thus, TGF-beta-induced EMT is not
      sufficient for the acquisition of the invasive potential and activated Ras alters
      this TGF-beta response, conferring the tumorigenic and invasive potential.

PMID- 19177010
TI  - Interleukin-6 affects cell death escaping mechanisms acting on Bax-Ku70-Clusterin
      interactions in human colon cancer progression.
AB  - Activation of pro-survival pathways and apoptotic cell death escape are
      considered hallmarks of oncogenic cell transformation. Tissue microenvironment
      strongly influences tumorigenesis, redirecting some pathways versus a persisting
      pro-survival state. Here, we report evidence on the role of interleukin 6 (IL-6)
      in affecting pro-survival pathways in colon cancer progression, modulating the
      expression and the molecular interactions among the pro-apoptotic factor Bax, the
      DNA repair proteins Ku70/86 and Clusterin isoforms. In human colorectal
      carcinomas (n = 50) at different stages of disease, we found an increased IL-6
      production, the loss of Ku86 and Clusterin 50-55 kDa pro-apoptotic isoform.
      Conversely, we observed the overexpression of Bax and the 40 kDa prosurvival
      sClusterin (sCLU) isoform. Bax co-localized with Ku70 that was found atypically
      expressed in the cytoplasm of advanced stage colon cancers (Dukes'C-D; n = 22).
      IL-6 treatment of a colon cancer cell line, Caco-2, modulated the expression of
      genes involved in tumor invasion and apoptosis, as observed by microarrays. In
      particular, IL-6 downmodulated Bax expression at mRNA level. Concomitantly, IL-6
      exposure influenced Bax also at protein level acting on the Bax-Ku70-sCLU
      physical interactions in the cytoplasm, by affecting the Ku70 acetylation and
      phosphorylation state, thus leading to the inhibition of Bax pro-apoptotic
      activity. In addition, we found that IL-6 treatment induced a significant
      downregulation of Ku86 and a strong increase of sCLU, confirming tumor biopsies
      data. In contrast Somatostatin treatment of Caco-2 cells was able to restore
      apoptosis, demonstrating that Ku70-Bax-CLU interactions could be dynamically
      modulated. Hence, IL-6 could favor tumor expansion, promoting cell survival and
      apoptosis escape throughout the different stages of tumor evolution. Uncovering
      the molecular mechanisms of action of these factors may offer strategies for
      selectively manipulate the cancer cells sensitivity to therapy.

PMID- 19177012
TI  - Pro-apoptotic function of checkpoint kinase-2 in syncytia elicited by the HIV-1
      envelope.
AB  - Fusogenic HIV-1 isolates induce the fusion of infected and bystander cells. Such
      syncytia can be found as "multinucleated giant cells" in the brain from HIV-1
      infected individuals, as well as in lymphoid tissues. Syncytia elicited by the
      HIV-1 envelope glycoprotein (Env) manifest the aggregation of PML in discrete
      nuclear bodies and the recruitment of TopBP1, NBS1 and ATM to DNA damage foci
      containing phosphorylated ATM and histone H2AX ("-H2AX). This DNA damage response
      then culminates in p53-dependent activation of the mitochondrial pathway of
      apoptosis. Here, we show that Env-elicited syncytia also manifest activating
      phosphorylations of the checkpoint kinases 1 and 2 (Chk1 and Chk2), and both Chk1
      and Chk2 colocalize with "-H2AX foci. However, only the siRNA-mediated knockdown
      of Chk2, not the depletion of Chk1, inhibits mitochondrial outer membrane
      permeabilization and subsequent syncytial apoptosis. Depletion of PML, TopBP1,
      NBS1 or ATM inhibit the activating phosphorylation of Chk2. Altogether, these
      results indicate that Chk2 (but not Chk1) participates in the DNA damage-elicited
      pro-apoptotic cascade that leads to the demise of Env-elicited syncytia.

PMID- 19177013
TI  - Targeting CDC37: an alternative, kinase-directed strategy for disruption of
      oncogenic chaperoning.
AB  - Interest in HSP90 inhibitors has grown rapidly in the last decade. The heightened
      dependence of malignant cells on molecular chaperones to maintain multiple
      oncogenic signalling pathways gives HSP90 broad anticancer appeal. New HSP90
      directed agents are continually emerging, several of which are under clinical
      evaluation. In parallel, dissection of the functional mechanism of the chaperone
      system has emphasised the importance of cochaperones that regulate HSP90. As we
      begin to fully elucidate the roles of these HSP90 accessory proteins, it is
      becoming increasingly clear that they too have potential as additional routes to
      disrupt chaperone activity. CDC37, a predominantly kinase client-associated
      cochaperone that promotes malignant transformation, has particular promise.
      Recently, we demonstrated that, similar to HSP90 inhibitors, siRNA-mediated CDC37
      silencing caused the proteasomal degradation of kinase client proteins and
      inhibited the proliferation of cancer cells. Importantly, depleting CDC37 does
      not induce the unwanted, antiapoptotic heat shock response that is characteristic
      of pharmacologic HSP90 inhibition. Furthermore, CDC37 silencing sensitises cancer
      cells to HSP90 inhibitors by potentiating kinase client depletion and the
      induction of apoptosis, suggesting that simultaneously modulating HSP90 and CDC37
      could be beneficial. Here we discuss the therapeutic possibilities of targeting
      CDC37 for cancer treatment in light of recent significant findings.

PMID- 19177015
TI  - Replication stress activates DNA polymerase alpha-associated Chk1.
AB  - Chk1 contributes to both intra-S and DNA damage checkpoint responses. Here, we
      show that depletion of DNA Polalpha and not Polepsilon or Poldelta by siRNA
      induces phosphorylation of Chk1 on Ser345, thus phenocopying antimetabolite
      exposure. Combinatorial ablation of DNA Polalpha and Chk1 causes an accumulation
      of gamma-H2A.X, a marker of double-strand DNA breaks, suggesting that activation
      of Chk1 in this context is essential for suppression of DNA damage. Co-depletion
      of DNA Polalpha with ATR yields similar phenotypes, suggesting that ATR and Chk1
      are epistatic and required for maintenance of genomic integrity following
      replication stress. Significantly, Chk1 and DNA Polalpha can be co
      immunoprecipated from native cell extracts. Moreover, following replication
      stress, Polalpha-associated Chk1 becomes rapidly phosphorylated on Ser345 in a
      TopBP1 and ATR-dependent manner. Hence, the ability to efficiently phosphorylate
      Chk1 in the context of DNA Polalpha complexes is correlated with suppression of
      DNA damage following replication stress. These findings identify DNA Polalpha as
      an important component of the signal transduction cascade that activates the
      intra-S checkpoint.

PMID- 19177014
TI  - Autophagy in mineralizing tissues: microenvironmental perspectives.
AB  - Chondrocytes in the growth plate and articular cartilage and osteocytes subsumed
      in Haversian bone exist in environmental niches that are characterized by a
      limited oxygen supply. In these tissues, cells display a hitherto unrecognized
      state in which there is evidence of autophagy. The autophagic condition serves to
      promote cell survival. When the response is triggered, the cell cannibalizes
      itself to generate energy; if extended, then it can activate Type II apoptosis.
      We opine that survival is dependent on niche conditions and regulated by
      crosstalk between mTOR, AMPK and HIF-1 and HIF-2. Recent studies suggest that HIF
      2 is a potent regulator of chondrocyte autophagy and that this protein acts as a
      brake to the stimulatory function of HIF-1. Accordingly, the oxemic state of the
      tissue, its nutrient supply as well as the energetic state of the cells regulates
      autophagic flux. From a clinical viewpoint, it may be possible to enhance
      skeletal cell survival through drugs that modulate the autophagic state and
      prevent the induction of apoptosis.

PMID- 19177016
TI  - A new link between epigenetic progenitor lesions in cancer and the dynamics of
      signal transduction.
AB  - Our recent study of the mechanism by which an epigenetic alteration, loss of
      imprinting (LOI) of Igf2, increases tumor risk, revealed a strong relationship
      between IGF2 dosage, the dynamics of signaling along the IGF2 axis, cell
      proliferation and tumor risk.(1) Colon epithelia in a mouse model with LOI of
      Igf2 showed increased sensitivity to IGF1R blockade and abrogation of
      premalignant lesion development in LOI(+) mice. These results are consistent with
      the epigenetic progenitor model of cancer,(2) in which epigenetic changes precede
      and heighten risk of cancer in response to oncogenic mutations. Thus, one can
      envision a highly targeted and focused chemoprevention strategy targeted to
      signaling pathways in nonmalignant cells that have undergone an epigenetic
      lesion, rather than a broad approach toward reversing epigenetic lesions that may
      have unintended consequences affecting the whole epigenome.

PMID- 19177017
TI  - Single-vector inducible lentiviral RNAi system for oncology target validation.
AB  - The use of RNA interference (RNAi) has enabled loss-of-function studies in
      mammalian cancer cells and has hence become critical for identifying and
      validating cancer drug targets. Current transient siRNA and stable shRNA systems,
      however, have limited utility in accurately assessing the cancer dependency due
      to their short-lived effects and limited in vivo utility, respectively. In this
      study, a single-vector lentiviral, Tet-inducible shRNA system (pLKO-Tet-On) was
      generated to allow for the rapid generation of multiple stable cell lines with
      regulatable shRNA expression. We demonstrate the advantages and versatility of
      this system by targeting two polycomb group proteins, Bmi-1 and Mel-18, in a
      number of cancer cell lines. Our data show that pLKO-Tet-On-mediated knockdown is
      tightly regulated by the inducer tetracycline and its derivative, doxycycline, in
      a concentration- and time-dependent manner. Furthermore, target gene expression
      is fully restored upon withdrawal of the inducing agent. An additional, 17
      distinct gene products have been targeted by inducible shRNAs with robust
      regulation in all cases. Importantly, we functionally validate the ability of the
      pLKO-Tet-On vector to reversibly silence targeted transcripts in vivo. The
      versatile and robust inducible lentiviral RNAi system reported herein can
      therefore serve as a powerful tool to rapidly reveal tumor cell dependence.

PMID- 19177018
TI  - Handcuff for sisters: a new model for sister chromatid cohesion.
AB  - High fidelity chromosome transmission requires the pairing of sister chromatids
      by a group of conserved proteins called cohesins during S-phase. Sister chromatid
      cohesion is maintained until anaphase onset. Presently, there are two sets of
      models of cohesin complex popular in the cohesin biology field: one model
      predicts that single cohesin rings entrap both sister chromatids, and the other
      model proposes that cohesin complexes associate with each sister chromatid and
      become paired during DNA replication. It is the first model that currently
      predominate the field--in part because prior efforts failed to detect higher
      order cohesin-cohesin interactions. However, the static configuration and size
      limitation of the one ring embrace model are the major limitations of the embrace
      model, and cannot explain various functions of cohesin in DNA replication, DNA
      repair and gene expression. In a recent study published by Zhang et al. in the
      Journal of Cell Biology describes a two-ring handcuff model for the cohesin
      complex, and provides new information regarding how sister chromatid cohesion and
      separation are achieved in vertebrate cell systems.

PMID- 19177019
TI  - HIV type 1 infection, and not short-term HAART, induces endothelial dysfunction.
AB  - OBJECTIVE: Ischemic cardiovascular events increasingly occur during long-lasting
      HIV infection and are attributed either to the infection itself or to the use of
      HAART. Endothelial dysfunction and platelet activation are markers of
      atherosclerosis. Our aim was to assess whether patients with chronic HIV
      infection present endothelial dysfunction and whether this is the consequence of
      infection or of HAART. DESIGN: Fifty-six HIV-infected patients were studied in a
      retrospective cohort study before and 3, 6, 12 and 24 months after starting HAART
      with protease inhibitors (n = 28) or nonnucleoside reverse transcriptase
      inhibitors (n = 28), and compared with 28 age-matched and sex-matched healthy
      controls, and with 10 naive HIV-infected patients studied at diagnosis and after
      12 months of untreated infection. METHODS: Soluble endothelial and platelet
      activation markers were measured in plasma by flow cytometry. RESULTS: Soluble P
      selectin, soluble vascular cell adhesion molecule-1, monocyte chemoattractant
      protein-1 and von Willebrand factor were significantly higher in HIV-infected
      patients than in healthy controls, whereas soluble CD40 ligand and tissue type
      plasminogen activator were within normal range. During follow-up, soluble
      vascular cell adhesion molecule-1, monocyte chemoattractant protein-1 and von
      Willebrand factor but not soluble P-selectin decreased progressively, without
      significant differences between protease inhibitors and nonnucleoside reverse
      transcriptase inhibitors treatment. In naive, untreated patients, increased
      plasma markers of endothelial dysfunction were confirmed at diagnosis, with no
      changes upon follow-up. CONCLUSION: Chronic HIV infection, and not its
      pharmacological treatment, induces alterations of markers of endothelial
      function. Short-term treatment with HAART reduces some markers of endothelial
      dysfunction, with no differences between protease inhibitors and nonnucleoside
      reverse transcriptase inhibitors.

PMID- 19177020
TI  - Phase II trial of infusional fluorouracil, leucovorin, oxaliplatin, and
      irinotecan (FOLFOXIRI) as first-line treatment for advanced gastric cancer.
AB  - The efficacy of chemotherapy for advanced gastric cancer with palliative intent
      compared with supportive care alone is now widely accepted. However, the best
      choice of chemotherapy regimen for patients with advanced gastric cancer is still
      a matter of controversy and requires further investigation. This study is
      performed to evaluate the efficacy and safety of the FOLFOXIRI regimen
      (oxaliplatin 85 mg/m as a 2-h intravenous infusion, irinotecan 165 mg/m as a 90
      min infusion, leucovorin 200 mg/m as a 2-h infusion, 5-fluorouracil 3200 mg/m as
      a 48-h continuous infusion on day 1, every 2 weeks) as first-line treatment for
      advanced gastric cancer. Forty-seven (95.9%) of the 49 patients were assessable
      for response. Two cases of complete response and 29 cases of partial response
      were confirmed, giving an overall response rate of 63.3% [95% confidence interval
      (CI): 49.8-76.8%]. The median time to progression and overall survival for all
      patients were 7.3 months (95% CI: 6.0-8.6 months) and 11.9 months (95% CI: 9.4
      14.4 months), respectively. The estimate of overall survival at 12 months was
      42.9% (95% CI: 29.0-56.7%). Most patients experienced neutropenia during their
      course of therapy with 49% of patients (n=23) for grade 3/4 neutropenia. Grade 3
      nausea/vomiting, stomatitis, and diarrhea were observed in 20 (42.6%), two
      (4.3%), and five (10.6%) patients, respectively. Yet, no grade 4 nonhematologic
      toxicity was observed. The FOLFOXIRI combination is a tolerated treatment
      modality with promising activity in previously untreated advanced gastric cancer
      patients.

PMID- 19177021
TI  - Resorufin: a lead for a new protein kinase CK2 inhibitor.
AB  - Screening a natural compound library led to the identification of resorufin as a
      highly selective and potent inhibitor of protein kinase CK2. Out of 52 kinases
      tested, only CK2 was inhibited, in contrast to emodin, a structurally related,
      known CK2 inhibitor that, in addition to CK2, inhibited ten other kinases by 90%.
      The IC50 values determined for the CK2 holoenzymes were 1.5 mol/l and for the
      free catalytic subunits ca. 4 mol/l. Altogether four cell lines were subjected to
      resorufin and emodin treatment. In the case of the three prostate carcinoma cell
      lines (PC-3, DU-145, LNCaP), 24 h treatment with 40 mol/l resorufin led to 15-20%
      dead cells; however, no caspase-mediated apoptosis was observed. In the case of
      the colorectal carcinoma HCT116 cell line, a similar picture was obtained, yet,
      when resorufin was administered to cells treated with doxorubicin, apoptosis was
      strongly induced within 24 h. Endogenous protein kinase CK2 was inhibited by
      resorufin by ca. 80% in the three prostate cell lines. In the case of the HCT116
      cells, the inhibition was only 40% supporting the notion of cell line-specific
      selectivity. Moreover, we analysed the effect of resorufin and emodin on selected
      signalling molecules in the cell lines under investigation.

PMID- 19177022
TI  - Gemcitabine, irinotecan and celecoxib in patients with biliary cancer.
AB  - The incidence of hepatobiliary cancers is increasing and no standard therapy
      currently exists. Gemcitabine is an active drug in this disease. Previous studies
      suggest that the combination of gemcitabine and irinotecan is active with
      reasonable toxicity profiles in pancreatic and hepatobiliary cancers. COX-2
      induction and overexpression have been documented in biliary dysplasia and
      biliary malignancies. We report on a case series of the efficacy and toxicity of
      gemcitabine plus irinotecan plus celecoxib in patients with advanced biliary
      cancer. The treatment consisted of gemcitabine 1000 mg/m given intravenously on
      days 1 and 8, irinotecan 100 mg/m given intravenously on days 1 and 8, and
      celecoxib 400 mg orally twice daily every 21 days. Six patients were enrolled,
      one was ineligible, therefore data were examined on the five remaining patients.
      One patient had a complete response, one had a partial response, two had stable
      disease, and one received one cycle of treatment and decided on surgery hence
      could not be assessed. The treatment was well tolerated with one grade 4 adverse
      event of thrombocytopenia. In conclusion, the combination of gemcitabine,
      irinotecan, and celecoxib appears to be well tolerated with some activity against
      biliary cancer. Further studies using this combination are warranted.

PMID- 19177023
TI  - Exposure to ionizing radiation in adulthood and thyroid cancer incidence.
AB  - BACKGROUND: Recent reviews of the radiation epidemiology literature have
      concluded that there is little evidence that exposure to ionizing radiation in
      adulthood causes thyroid cancer. This paper examines the association between
      radiation dose and thyroid cancer incidence among Japanese survivors who were
      adults at the time of the atomic bombings of Hiroshima and Nagasaki. METHODS:
      Analyses were conducted using data on cancer incidence during the period 1958
      1998 among 59,687 members of the Life Span Study of atomic bomb survivors who
      were 20 years or older at time of bombings of Hiroshima and Nagasaki. Poisson
      regression methods were used to derive estimates of associations between thyroid
      dose in gray (Gy) and thyroid cancer incidence by sex, age at exposure, and time
      since-exposure. RESULTS: The number of thyroid cancer cases among women (n = 241)
      was nearly 5-fold the number of cases among men (n = 55). Estimated thyroid dose
      was positively associated with thyroid cancer incidence among women A-bomb
      survivors (excess relative rate/Gy = 0.70; 90% confidence interval = 0.20-1.46).
      In contrast, a negative association was observed between thyroid dose and thyroid
      cancer among men (excess relative rate/Gy = -0.25; <0 to 90% confidence interval
      = 0.35). The association among women was positive for all time-since-exposure
      periods examined but tended to diminish in magnitude with time-since-exposure.
      CONCLUSIONS: Exposure to ionizing radiation in adulthood was positively
      associated with thyroid cancer among women A-bomb survivors, although the risk
      seems to be lower than for those exposed to radiation in childhood.

PMID- 19177025
TI  - Estimating denominators: satellite-based population estimates at a fine spatial
      resolution in a European urban area.
AB  - BACKGROUND: There is a need for alternative approaches to obtain population
      denominators when census information is unavailable, unreliable, or not available
      at the appropriate spatial resolution. The aim of this study is to develop an
      exportable population model, based on a single satellite-derived indicator, for
      estimating fine-scale population data and characterizing high-incidence areas in
      an urbanized area. METHODS: A Landsat 7 enhanced thematic mapper plus image was
      processed to generate population density indices at the block and block-group
      levels, using both an unsupervised pixel-based and a supervised classification.
      Spatial disaggregation was used to calculate population estimates, distributing
      the total population of the city of Besanon (France) into census areas by means
      of their respective population density indices. Accuracy assessment was performed
      through comparisons with census counts. RESULTS: At the block-group level, the
      simplest model produced relatively accurate and reliable population estimates
      within the range of observed counts. A strong agreement was found between
      observed and estimated incidence rates for non-Hodgkin lymphoma (intraclass
      correlation coefficient [ICC] = 0.73), but not for female breast cancer (ICC =
      0.40). Withdrawing the sprawled block groups improved the agreements considerably
      (ICC = 0.84 and 0.71, respectively). CONCLUSIONS: This apportioning procedure
      offers a way to obtain estimated population sizes (or at least densities) for
      areas with no accurate census, but does not substitute for censuses where good
      census data exist. Because it is rapid, relatively cheap, and computationally
      easy, it should be of special interest to epidemiologists, environmental
      scientists, and public health decision makers.

PMID- 19177024
TI  - Missing data in a long food frequency questionnaire: are imputed zeroes correct?
AB  - BACKGROUND: Missing data are a common problem in nutritional epidemiology. Little
      is known of the characteristics of these missing data, which makes it difficult
      to conduct appropriate imputation. METHODS: We telephoned, at random, 20% of
      subjects (n = 2091) from the Adventist Health Study-2 cohort who had any of 80
      key variables missing from a dietary questionnaire. We were able to obtain
      responses for 92% of the missing variables. RESULTS: We found a consistent excess
      of "zero" intakes in the filled-in data that were initially missing. However, for
      frequently consumed foods, most missing data were not zero, and these were
      usually not distinguishable from a random sample of nonzero data. Older, black,
      and less-well-educated subjects had more missing data. Missing data are more
      likely to be true zeroes in older subjects and those with more missing data. Zero
      imputation for missing data may create little bias except for more frequently
      consumed foods, in which case, zero imputation will be suboptimal if there is
      more than 5%-10% missing. CONCLUSIONS: Although some missing data represent true
      zeroes, much of it does not, and data are usually not missing at random.
      Automatic imputation of zeroes for missing data will usually be incorrect,
      although there is [corrected] little bias unless the foods are frequently
      consumed. Certain identifiable subgroups have greater amounts of missing data,
      and require greater care in making imputations.

PMID- 19177026
TI  - Present-day prehospital airway management in the former Eastern German state of
      Thuringia: equipment and education of emergency physicians.
AB  - We describe the condition of education and equipment regarding prehospital airway
      management in the German federal state of Thuringia, representing a part of
      former Eastern Germany. In 2006 a postal survey of the 39 emergency medical
      stations (EMS) in Thuringia was carried out. The response rate was 100%. In 72%
      of the EMS, a device for extraglottic airway management and in all EMS a device
      for cricothyrotomy was available. A device to monitor end-tidal CO2 was available
      in 41%. Difficulties in airway management in the past two years were reported
      from 74% of the EMS. Ongoing training and education in airway management is
      provided in 82% of the emergency districts. This survey reveals wide variations
      in the equipment for airway management available to prehospital emergency
      physicians in Thuringia. Given the reported difficulties in airway management,
      availability of a more standardized set of airway management devices in Thuringia
      may be helpful.

PMID- 19177027
TI  - Perihepatic lymph nodes as markers of disease response in patients with hepatitis
      C-related liver disease: a prospective clinical evaluation.
AB  - AIM: To assess the clinical feasibility of utilizing the presence of perihepatic
      lymphadenopathy, seen on ultrasound, as a marker of response to antiviral
      treatment in patients with hepatitis C virus (HCV)-related liver disease.
      METHODS: Eighty-five patients with HCV-related liver disease [51 men and 34
      women; mean age 47 years (range 26-67)] underwent liver biopsy and baseline
      ultrasound scans. Twenty-two of these patients were followed up longitudinally
      with 6-monthly ultrasound scans, whereas they were receiving anti-HCV eradication
      therapy with interferon and ribavirin. Perihepatic lymph nodes detected in the
      coeliac axis and peripancreatic region were noted, with the largest node size on
      maximal diameter recorded. The patients were subsequently assessed in the light
      of long-term virological response to treatment. RESULTS: Perihepatic lymph nodes
      were detected in 26 of the 85 patients. Of the 22 patients followed up
      longitudinally, 11 responded to antiviral treatment, nine failed to respond and
      two did not complete a course of treatment. No significant difference was found
      between patients with detectable lymphadenopathy and those without according to
      age, sex, disease severity and genotype. There was a general reduction in size of
      lymph nodes in both responders and nonresponders to treatment, although this
      reduction was only significant in the responder group (P=0.003). CONCLUSION: The
      presence of perihepatic lymphadenopathy when detected in patients with viral
      hepatitis can potentially serve as an indicator of response to treatment.
      However, as only 30-40% of patients have detectable lymphadenopathy, its clinical
      utility is limited.

PMID- 19177028
TI  - Surveillance of Barrett's columnar-lined oesophagus in the UK: endoscopic
      intervals and frequency of detection of dysplasia.
AB  - OBJECTIVES: Endoscopic surveillance of patients with columnar-lined oesophagus
      (CLO) may identify those with early adenocarcinoma (AC). The benefits of
      surveillance are unproven and there is little evidence to support recommendations
      for precise endoscopic intervals. We sought to examine surveillance practice for
      CLO in the UK and the impact of endoscopic intervals on detection of dysplastic
      disease. METHODS: Eight hundred and seventeen patients with CLO, registered with
      the UK National Barrett's Oesophagus registry and undergoing surveillance were
      studied. Endoscopic intervals were calculated and frequency of detection of
      dysplastic disease analysed using chi2 test of association. Factors affecting
      surveillance intervals were analysed using multiple linear regression. RESULTS:
      94.7% of patients with low-grade dysplasia (LGD), 95.0% with high-grade dysplasia
      (HGD) and 71.4% with AC were diagnosed on surveillance endoscopies. Mean
      endoscopic surveillance intervals varied between the centres from 1.07 to 1.63
      years for nondysplastic CLO; 0.69-1.19 years for LGD, and 0.35-1.17 years for
      HGD; with overall mean surveillance intervals of 1.29, 1.01 and 0.44 years,
      respectively. When LGD was surveyed, significantly higher proportions of HGD/AC
      were detected at intervals of 3 months or less (P=0.013). Shorter endoscopic
      intervals were significantly associated with the presence of oesophageal
      strictures (P=0.002), ulcers (P=0.046), increasing patient age (P<0.001) and
      higher grade of dysplasia surveyed (P<0.001). CONCLUSION: A variation in
      surveillance practice for CLO was observed throughout the UK. A large proportion
      of dysplastic disease is detected on specific surveillance endoscopies. Shorter
      endoscopic intervals for surveillance of LGD are associated with an increased
      detection of HGD/AC.

PMID- 19177029
TI  - Validation of VKORC1 and CYP2C9 genotypes on interindividual warfarin maintenance
      dose: a prospective study in Chinese patients.
AB  - OBJECTIVES: To develop a warfarin-dosing algorithm that could be combined with
      pharmacogenomic and demographic factors, and to evaluate its effectiveness in a
      randomized prospective controlled clinical trial. METHODS: A pharmacogenetics
      based dosing model was derived using retrospective data from 266 Chinese patients
      and multiple linear regression analysis. To prospectively validate this model,
      156 patients with an operation of heart valve replacement were enrolled and
      randomly assigned to the group of pharmacogenetics-guided or traditional dosing
      for warfarin therapy. All patients were followed up for 50 days after initiation
      of warfarin therapy. The log-rank test was compared with the time-to-event
      (Kaplan-Meier) curves. Cox proportional hazards-regression model was used to
      assess the hazard ratio of the time to reach stable dose. RESULTS: The linear
      regression model derived from the pharmacogenomic model correlated with 54.1% of
      warfarin dosing variance. The final multiple linear regression model included
      age, body surface area, VKORC1, and CYP2C9 genotype. The study showed that the
      hazard ratio for the time to reach stable dose was 1.932 for the traditional
      dosing group versus the model-based group and a close and highly significant
      relationship was observed to exist between the predicted and the actual warfarin
      dose (R=0.454). CONCLUSION: A pharmacogenetics-based dosing algorithm has been
      developed for improvement in the time to reach the stable dosing of warfarin.
      This model may be useful in helping the clinicians to prescribe warfarin with
      greater safety and efficiency.

PMID- 19177030
TI  - Ethanol intake and ethanol-induced locomotion and locomotor sensitization in
      Cyp2e1 knockout mice.
AB  - OBJECTIVES: It has been shown that acetaldehyde is an active metabolite of
      ethanol with central actions that modulate behavior. Catalase has been proposed
      as the main enzyme responsible for the synthesis of acetaldehyde from ethanol in
      the brain. Recent studies, however, suggest that cytochrome, in particular the
      isoform P450 2E1, can also contribute to the central metabolism of ethanol.
      METHODS: Cytochrome P4502E1 knockout (KO) mice were used to assess the
      involvement of this isoenzyme in some of the acute and chronic behavioral effects
      of ethanol. Ethanol-induced locomotion, locomotor sensitization, and voluntary
      ethanol intake were evaluated in cytochrome P4502E1 KO mice and their wild-type
      (WT) counterparts. RESULTS: Spontaneous locomotion in KO mice was lower than that
      seen in the WT mice. Acute administration of ethanol (1.5 g/kg,
      intraperitoneally) increased locomotion to a similar extent in both strains of
      mice. Repeated intermittent administration of ethanol produced sensitization in
      both strains, but it was very subtle in the KO mice compared with the effect in
      the WT mice. KO mice showed a reduction in preference for ethanol intake at low
      concentrations (4-8% v/v). Interestingly, western blot for catalase in the brain
      and liver showed that KO mice had higher levels of catalase expression compared
      with WT mice. CONCLUSION: These results show some impact of the mutation on
      ethanol-induced sensitization and on voluntary ethanol preference. The lack of a
      substantial impact of the mutation can be explained by the fact that the KO
      animals have a compensatory increase in catalase expression compared with WT
      mice, therefore possibly showing alterations in the formation of acetaldehyde
      after ethanol administration.

PMID- 19177031
TI  - Opportunities to optimize tacrolimus therapy in solid organ transplantation:
      report of the European consensus conference.
AB  - In 2007, a consortium of European experts on tacrolimus (TAC) met to discuss the
      most recent advances in the drug/dose optimization of TAC taking into account
      specific clinical situations and the analytical methods currently available and
      drew some recommendations and guidelines to help clinicians with the practical
      use of the drug. Pharmacokinetic, pharmacodynamic, and more recently
      pharmacogenetic approaches aid physicians to individualize long-term therapies as
      TAC demonstrates a high degree of both between- and within-individual
      variability, which may result in an increased risk of therapeutic failure if all
      patients are administered a uniform dose. TAC has undoubtedly benefited from
      therapeutic drug monitoring, but interpretation of the blood concentration is
      confounded by the relative differences between the assays. Single time points,
      limited sampling strategies, and area under concentration-time curve have all
      been considered to determine the most appropriate sampling procedure that
      correlates with efficacy. Therapeutic trough TAC concentration ranges have
      changed since the initial introduction of the drug, while still maintaining
      adequate immunosuppression and avoiding drug-related adverse effects.
      Pharmacodynamic markers have also been considered advantageous to the clinician,
      which may better reflect efficacy and safety, taking into account the between
      individual variability rather than whole blood concentrations. The choice of
      method, differences between methods, and potential pitfalls of the method should
      all be considered when determining TAC concentrations. The recommendations of
      this consensus meeting regarding the analytical methods include the following:
      encourage the development and promote the use of analytical methods displaying a
      lower limit of quantification (1 ng/mL), perform careful validation when
      implementing a new analytical assay, participate in external proficiency testing
      programs, promote the use of certified material as calibrators in high
      performance liquid chromatography with mass spectrometric detection methods, and
      take account of the assay and intermethod bias when comparing clinical trial
      outcomes. It is also important to consider that TAC concentrations may also be
      influenced by other factors such as specific pharmacokinetic characteristics
      associated with the population, drug interactions, pharmacogenetics, adverse
      events that may alter TAC concentrations, and any change in the oral formulation
      that may result in pharmacokinetic changes. This meeting emphasized the
      importance of obtaining multicenter prospective trials to assess the efficacy of
      alternative strategies to TAC trough concentrations whether it is other single
      time points or area under the concentration-time curve Bayesian estimation using
      limited sampling strategies and to select, standardize, and validate routine
      biomarkers of TAC pharmacodynamics.

PMID- 19177032
TI  - A critical review: does thiopental continuous infusion warrant therapeutic drug
      monitoring in the critical care population?
AB  - Thiopental is a barbiturate used in traumatic brain injuries (TBIs) to reduce
      intracranial pressure (ICP) and to manage cerebral ischemia. As thiopental
      follows Michaelis-Menten kinetics, therapeutic drug monitoring (TDM) has been
      used in practice to improve efficacy and reduce adverse effects. However, its
      role is still debatable, and TDM is not widely practiced. Current evidence
      suggests that thiopental therapy may improve mortality and functional outcome in
      a subpopulation of patients with severe TBI with elevated ICP refractory to
      conventional medical therapy. Several analytical methods are available to
      quantify thiopental concentrations. This review uses a previously published 9
      step decision-making algorithm to determine whether TDM of thiopental in TBI is
      warranted. There seems to be poor correlation between thiopental concentration
      and pharmacological response in terms of neurological response, ICP,
      electroencephalography, and drug toxicity. There is no established therapeutic
      range for thiopental continuous infusion due to a wide range of plasma
      concentrations corresponding to efficacy (25-50 mg/L) and toxicity (30-70 mg/L)
      and the resulting overlap between the 2. Thiopental exhibits intrapatient and
      interpatient variability due to age, obesity, renal and hepatic dysfunction,
      Michaelis-Menten kinetics, and hepatic enzyme autoinduction. Available evidence
      suggests that TDM of thiopental continuous infusion is not beneficial in
      improving efficacy or avoiding toxicity. There are however 2 possible scenarios
      in which TDM may provide additional information to sound clinical judgment. The
      first is providing patient-specific plasma target concentration to guide
      titration of therapy. The second scenario is differentiating between brain death
      and barbiturate-induced coma.

PMID- 19177033
TI  - Testicular nodules in a 16-year-old boy.

PMID- 19177038
TI  - Assisted reproductive technology and trends in low birthweight--Massachusetts,
      1997-2004.
AB  - Low birthweight (LBW) (<2,500 g) is an important cause of infant morbidity and
      mortality. The rate of LBW has been steadily increasing in the United States. In
      2005, the most recent year for which data are available, LBW represented 8.2% of
      all births, the highest level reported in the past 4 decades. The use of assisted
      reproductive technology (ART) has been associated with LBW. Research in 1999
      indicated that, in Massachusetts during 1989--1996, the rate of LBW increased,
      paralleling the national trend, and an increasing percentage of LBW infants were
      born to mothers aged >/=35 years and to mothers with more education. These
      findings suggested that a proportion of LBW births might be attributable to
      infertility treatment; however, at that time, no information was available from
      birth certificate records to examine whether ART was associated with the
      increasing rates of LBW. To investigate the role of ART, the Massachusetts
      Department of Public Health (MDPH) and CDC linked birth certificate records to
      ART records for the years 1997--2004 (the most recent data available). This
      report summarizes the results of that analysis, which indicated that, on average,
      2% of births during the period resulted from ART; however, 7% of LBW births
      resulted from ART. The rate of LBW increased during this period among non-ART
      singletons (from 4.8% to 5.1%), accounting for an additional 407 LBW infants, and
      among ART singletons (from 6.4% to 8.2%), accounting for an additional 59 LBW
      infants. Although ART contributes disproportionately to LBW, only a small
      percentage of the excess LBW births in Massachusetts are explained by ART;
      therefore, other causes for the increase in LBW should be examined.

PMID- 19177039
TI  - Methicillin-resistant Staphylococcus aureus among players on a high school
      football team--New York City, 2007.
AB  - On September 12, 2007, the New York City Department of Health and Mental Hygiene
      (DOHMH) was notified of three players on a Brooklyn high school football team
      with culture-confirmed methicillin-resistant Staphylococcus aureus (MRSA) skin
      and soft tissue infections (SSTIs). During August 19--24, the team had attended a
      preseason football training camp, where all 59 players on the team lived together
      in the school gymnasium. An investigation by DOHMH revealed four culture
      confirmed and two suspected cases of MRSA among 51 players interviewed (11.8%
      attack rate). Of the six cases, three involved abscesses that required incision
      and drainage. The risk for MRSA infection was higher among those who shared
      towels during the training camp than among those who did not (relative risk [RR]
      = 8.2). In addition, the six players with MRSA infections had a mean body mass
      index (BMI) that was significantly higher than the mean for those who were not
      infected. Multivariable logistic modeling determined that sharing towels during
      camp (adjusted odds ratio [AOR] = 15.7) and higher BMI (AOR = 1.4) were
      associated independently with MRSA infection. Similar outbreaks have been
      reported among football teams in which inadequate hygiene, combined with skin
      injuries and living in close quarters, contributed to the spread of MRSA
      infection. Such outbreaks might be prevented by better educating players and
      coaches regarding SSTIs and by better promoting proper player hygiene,
      particularly during training camps.

PMID- 19177040
TI  - Children with elevated blood lead levels related to home renovation, repair, and
      painting activities--New York State, 2006-2007.
AB  - Although blood lead levels (BLLs) >/=10 microg/dL are associated with adverse
      behavioral and developmental outcomes, and environmental and medical
      interventions are recommended at >/=20 microg/dL, no level is considered safe. A
      1997 analysis conducted by the New York State Department of Health (NYSDOH)
      indicated that home renovation, repair, and painting (RRP) activities were
      important sources of lead exposure among children with BLLs >/=20 microg/dL in
      New York state (excluding New York City) during 1993--1994. Subsequently, local
      health departments in New York state began to routinely collect information about
      RRP activities when investigating children's home environments for lead sources.
      This report updates the 1997 analysis with data from environmental investigations
      conducted during 2006--2007 in New York state (excluding New York City) for 972
      children with BLLs >/=20 microg/dL. RRP activities were identified as the
      probable source of lead exposure in 139 (14%) of the 972 children. Resident
      owners or tenants performed 66% of the RRP work, which often included sanding and
      scraping (42%), removal of painted materials or structures (29%), and other
      activities (29%) that can release particles of lead-based paint. RRP activities
      continued to be an important source of lead exposure during 2006--2007. Children
      living in housing built before 1978 (when lead-based paint was banned from
      residential use) that are undergoing RRP activities should be considered at high
      risk for elevated BLLs, and appropriate precautions should be taken to prevent
      exposure.

PMID- 19177041
TI  - Invasive Haemophilus influenzae Type B disease in five young children--Minnesota,
      2008.
AB  - In 2008, five children aged <5 years were reported to the Minnesota Department of
      Health (MDH) with invasive Haemophilus influenzae type b (Hib) disease; one died.
      Only one of the children had completed the primary Hib immunization series; three
      had received no doses of Hib-containing vaccine. The five Hib cases are the
      largest number among children aged <5 years reported from Minnesota since 1992.
      The cases occurred during a Hib vaccine recall and continuing nationwide shortage
      that began in December 2007. The recall of certain lots of the two Hib-containing
      vaccines manufactured by Merck Co., Inc. (West Point, Pennsylvania) and cessation
      of production of both vaccines left only one manufacturer of Hib vaccine in the
      United States (Sanofi Pasteur, Swiftwater, Pennsylvania). In response, CDC
      recommended that health-care providers defer the routine 12--15 month booster
      dose for children not at increased risk for Hib disease. CDC also emphasized that
      all children should complete the primary series with available Hib-containing
      vaccines. However, Minnesota vaccination data indicate that primary Hib series
      coverage was lower during 2008 than coverage with other vaccines administered at
      the same ages and lower than Hib coverage in previous years. Increases in Hib
      cases like the one in Minnesota do not appear to have occurred in other states.
      The increase highlights the need to ensure that all children complete the primary
      Hib immunization series. Additional investigation to better elucidate the factors
      that led to these cases is being conducted by MDH and CDC.

PMID- 19177042
TI  - External cephalic version: a terrible opportunity to waste.

PMID- 19177043
TI  - High-risk pregnancy management in women with hypopituitarism.
AB  - Pregnancy after complete loss of pituitary function is uncommon. However,
      advances in fertility treatment have led to increased pregnancy rates in
      hypopituitary women. We hereby present a literature review of pregnancies
      affected by hypopituitarism, including a comparison with published controls;
      further, we add one case report of severe hypopituitarism where third-trimester
      oxytocin supplementation was performed. As only limited information is available
      on management and outcome, our purpose was to determine obstetric complications
      associated with deficiency of pituitary hormones. The analysis of 31 pregnancies
      in 27 women revealed that hypopituitary women are at increased risk: postpartum
      hemorrhage occurred in 8.7%, transverse lie in 16%; 42.4% of the newborns were
      small for gestational age. These findings are supposedly the result of uterine
      dysfunction caused by hormone deficiency. Oxytocin supplementation was performed
      with the aim to establish physiologic conditions and to prevent postpartum
      uterine inertia. In this case substitution may have contributed to correct fetal
      presentation but did not prevent postpartum hemorrhage. Further investigations
      into both oxytocin-dependent and -independent mechanisms regulating uterine
      contractions and contractility are necessary to develop strategies for prevention
      of uterine inertia in oxytocin-deficient pregnancies.

PMID- 19177044
TI  - Repeated dosing of digoxin-fragmented antibody in preterm eclampsia.
AB  - Early onset eclampsia has significant morbidity and mortality for both the mother
      and fetus. No effective treatment exists at present except delivery and seizure
      prophylaxis with magnesium sulfate. We report the novel use of a fragmented ovine
      antibody against digoxin for the treatment of eclampsia. A 16-year-old
      primagravida at 29 weeks 5/7 days gestation presented with clinical diagnosis of
      eclampsia and was treated with compassionate off-label use of digoxin-fragmented
      ovine antibody (Digibind Glaxo Smith Kline, Research Triangle Park, NC, USA).
      Improvement of her underlying disorder during a 48 h treatment window was noted
      without adverse maternal or neonatal outcome. We suggest digoxin-fragmented ovine
      antibody as a possible intervention in preterm pregnancies complicated by pre
      eclampsia or eclampsia.

PMID- 19177045
TI  - Successful pregnancy and cesarean delivery via noninvasive ventilation in
      mitochondrial myopathy.
AB  - We report a case study of a 22-year-old woman with mitochondrial thymidine kinase
      2 deficiency and chronic respiratory failure due to severe neuromuscular weakness
      requiring noninvasive positive pressure ventilation (NIPPV) since 12 years of
      age. During pregnancy and cesarean delivery, she was successfully supported with
      NIPPV. A multidisciplinary team approach should be used in pregnant patients with
      these disorders with specific attention to management of pulmonary complications,
      selection of route of delivery, anesthesia, and analgesia.

PMID- 19177046
TI  - Late vitamin K deficiency bleeding after intramuscular prophylaxis at birth: a
      case report.
AB  - We report the case of a 6-week-old female who presented an intracranial
      hemorrhage due to late vitamin K deficiency bleeding (VKDB). No other evident
      bleeding sites were present at the moment of diagnosis. Intramuscular vitamin K
      (1 mg) was administered at birth. She was exclusively breast-fed. No other risk
      factors for VKDB were detected. Low levels of vitamin K-dependent coagulation
      factors and their normalization after vitamin K administration confirmed the
      diagnosis of late VKDB. The present case suggests potential risks related to a
      single dose of intramuscular vitamin K at birth.

PMID- 19177047
TI  - Phenotypic continuum of type 2 Gaucher's disease: an intermediate phenotype
      between perinatal-lethal and classic type 2 Gaucher's disease.
AB  - The natural history and clinical presentation of the perinatal-lethal Gaucher's
      disease, a severe variant of acute type 2 Gaucher's disease, is quite different
      from classic type 2 Gaucher's disease. Rare reported patients had an overlapping
      phenotype between these two forms confirming that phenotyping may be difficult.
      Here we report three patients with an intermediate phenotype. The first two
      patients showed at birth cholestatic jaundice, hepatosplenomegaly and
      hematological involvement consistent with hemophagocytosis in one patient, the
      death occurred from a severe liver involvement in one and lung disease in the
      second in the absence of neurological symptoms. The third patient displayed
      ichthyosis and facial dysmorphism but with neurological degeneration course and
      survival consistent with classic type 2 Gaucher's disease.

PMID- 19177048
TI  - Cervical ectopic thymus.

PMID- 19177049
TI  - Congenital intralobar pulmonary sequestration with cystic adenomatoid
      malformation.

PMID- 19177050
TI  - Congenital chylous ascites.

PMID- 19177053
TI  - Safer management of newborn jaundice.

PMID- 19177054
TI  - Calculated free bilirubin levels and neurotoxicity.
AB  - Although most bilirubin in the circulation is bound to albumin, a relatively
      small fraction remains unbound. The concentration of this 'free' bilirubin (B(F))
      is believed to dictate the biologic effects of bilirubin in jaundiced newborns,
      including its neurotoxicity. The threshold at which B(F) produces changes in
      cellular function culminating in permanent cell injury and cell death has been
      the subject of considerable debate. The objective of this study was to compare
      calculated central nervous system (CNS) B(F) levels in Gunn rat pups during (i)
      peak postnatal hyperbilirubinemia and (ii) sulfadimethoxine-induced acute
      bilirubin encephalopathy (ABE) previously reported from our laboratory with those
      predicted in human neonates with peak total serum bilirubin (TSB) levels of 35 mg
      per 100 ml (599 micromol l(-1)), a clinical cohort that often evidence moderate
      to-severe adverse post-icteric neurodevelopmental sequelae. Homozygous j/j Gunn
      rat pups with neonatal hyperbilirubinemia due to a deficiency of the bilirubin
      conjugating enzyme uridine-diphosphate-glucuronosyl transferase 1A1 were studied
      along with non-jaundiced littermate heterozygous J/j controls. Sulfadimethoxine
      was used to displace bilirubin from albumin in hyperbilirubinemic j/j Gunn rat
      pups to increase their brain bilirubin content and induce ABE. Calculated Gunn
      rat CNS B(F) levels were determined as a function of genotype, sulfadimethoxine
      exposure and albumin-bilirubin binding constant. These data were compared with
      the human CNS B(F) predicted from the calculated serum B(F) in human neonates
      with a TSB of 35 mg per 100 ml as a function of albumin-bilirubin binding
      constant, albumin concentration and the assumption that at this hazardous
      bilirubin level there may be rapid equilibration of B(F) between serum and brain.
      There was a large gap between the upper limit of the calculated CNS B(F) 95%
      confidence interval (CI) range in non-jaundiced J/j pups (for example, 112 nM at
      k=9.2 l micromol(-1)) and the lower limit seen in the saline-treated
      hyperbilirubinemic j/j pups (556 nM at k=9.2 l micromol(-1)) as well as between
      the upper limit in saline-treated hyperbilirubinemic j/j pups (1110 nM at k=9.2 l
      micromol(-1)) and the lower limit seen in sulfadimethoxine-treated jaundiced j/j
      littermates (3461 nM at k=9.2 l micromol(-1)). There was considerable overlap and
      remarkable similarity between the predicted human CNS B(F) values at a TSB of 35
      mg per 100 ml for a range of reported human serum bilirubin-albumin binding
      constants and albumin concentrations, and those calculated for saline-treated
      hyperbilirubinemic j/j Gunn rat pups. This exercise yielded strikingly similar
      apparent calculated neurotoxic B(F) levels for Gunn rat pups and human neonates
      rather than orders of magnitude differences that might have been predicted at the
      outset and add to a growing literature aimed at defining clinically germane
      neurotoxic B(F) thresholds.Journal of Perinatology (2009) 29, S14-S19;
      doi:10.1038/jp.2008.218.

PMID- 19177055
TI  - Commentary on the bilirubin supplement.

PMID- 19177056
TI  - Kernicterus in the 21st century: frequently asked questions.
AB  - Acute kernicterus remains a clinical emergency and its delayed management
      represents an easily preventable neonatal brain injury. Yet, practitioners
      encounter recurrent questions regarding the risk and timing of bilirubin-related
      neurotoxicity. These include the following: does bilirubin damage the brain of
      healthy infants? Is there a re-emergence of kernicterus in the United States? Was
      kernicterus previously prevented in the United States? What was the public health
      impact of 1994 American Academy of Pediatrics Guidelines? What is the current
      incidence of kernicterus and severe neonatal hyperbilirubinemia? What is the
      estimated risk of kernicterus in infants with excessive hyperbilirubinemia? Is
      there a specific bilirubin threshold total serum bilirubin (TSB) value for
      neurotoxicity? Are there sequelae of severe or prolonged moderate
      hyperbilirubinemia in the absence of recognized acute bilirubin encephalopathy?
      Can we define a bilirubin level that is safe in newborns? We address these
      questions in the context of available data and evidence, and estimate the current
      risk of chronic kernicterus is about one in seven in infants with TSB >30 mg per
      100 ml (513 micromol l(-1)).

PMID- 19177057
TI  - Clinical report from the pilot USA Kernicterus Registry (1992 to 2004).
AB  - To identify antecedent clinical and health services events in infants (>/=35
      weeks gestational age (GA)) who were discharged as healthy from their place of
      birth and subsequently sustained kernicterus. We conducted a root-cause analysis
      of a convenience sample of 125 infants >/=35 weeks GA cared for in US healthcare
      facilities (including off-shore US military bases). These cases were voluntarily
      reported to the Pilot USA Kernicterus Registry (1992 to 2004) and met the
      eligibility criteria of acute bilirubin encephalopathy (ABE) and/or post-icteric
      sequelae. Multiple providers at multiple sites managed this cohort of infants for
      their newborn jaundice and progressive hyperbilirubinemia. Clinical signs of ABE,
      verbalized by parents, were often inadequately elicited or recorded and often not
      recognized as an emergency. Clinical signs of ABE were reported in 7 of 125
      infants with a subsequent diagnosis of kernicterus who were not re-evaluated or
      treated for hyperbilirubinemia, although jaundice was noted at outpatient visits.
      The remaining infants (n=118) had total serum bilirubin (TSB) levels >20 mg per
      100 ml (342 micromol l(-1); range: 20.7 to 59.9 mg per 100 ml). No specific TSB
      threshold coincided with onset of ABE. Of infants <37 weeks GA with kernicterus,
      34.9% were LGA (large for gestational age) as compared with 24.7% of term infants
      (>37 weeks GA). Although >90% mothers initiated breast-feeding, assessment of
      milk transfer and lactation support was suboptimal in most. Mortality was 4% (5
      of 125) in infants readmitted at age </=1 week. Along with a rapid rise of TSB
      (>0.2 mg per 100 ml per hour), contributing factors, alone or in combination,
      included undiagnosed hemolytic disease, excessive bilirubin production related to
      extra-vascular hemolysis and delayed bilirubin elimination (including increased
      enterohepatic circulation, diagnosed and undiagnosed genetic disorders) in the
      context of known late prematurity (<37 weeks), glucose 6-phosphate-dehydrogenase
      deficiency, infection and dehydration. Readmission was at age </=5 days in 81 of
      118 (69%) infants and <10 days in 101 of 118 (86%) infants. TSB levels were </=35
      mg per 100 ml (598 micromol l(-1)) in 46 (39%) infants, of whom one died before
      exchange transfusion, one was untreated and one was lost to follow-up. Timely and
      efficacious bilirubin reduction interventions defined by 'crash-cart' initiation
      of immediate intensive phototherapy and urgent exchange transfusion were
      accomplished in 11 of 43 infants, which were compared with 12 of 43 infants in
      whom a timely exchange sometimes could not be accomplished. No overt sequelae
      were found in 8 of 11 infants (73%) treated with a 'crash-cart' approach compared
      with none without sequelae when exchange was delayed by pre-admission delays,
      technical factors or need to transfer to a tertiary facility. None of the
      remaining 20 of 43 infants treated only with phototherapy escaped sequelae.
      Regardless of age at readmission and intervention, infants with peak measured TSB
      >35 mg per 100 ml had post-icteric sequelae (n=73). There was a narrow margin of
      safety between birthing hospital discharge or home birth and readmission to a
      tertiary neonatal/pediatric facility. Progression of hyperbilirubinemia to
      hazardous levels and onset of neurological signs were often not identified as
      infant's care and medical supervision transitioned during the first week after
      birth. The major underlying root cause for kernicterus was systems failure of
      services by multiple providers at multiple sites and inability to identify the at
      risk infant and manage severe hyperbilirubinemia in a timely manner.

PMID- 19177058
TI  - Synopsis report from the pilot USA Kernicterus Registry.
AB  - Breakdown in systems for safe newborn health-care delivery accounts for the
      majority of kernicterus cases encountered in the United States. Traditional
      epidemiologic investigations do not track the national incidence of severe
      hyperbilirubinemia and kernicterus or recognize its recent surge. Innovative
      investigative strategies are needed to seek more sensitive surrogates for
      kernicterus (often diagnosed late in infancy) and to overcome the limitations of
      retrospective continuity of adverse neonatal experiences because of severe
      hyperbilirubinemia. Root cause analysis of a cohort of infants who manifested
      kernicterus in the past two decades attests to some of the clinical and health
      service barriers encountered by families as they negotiate health care from
      multiple providers at multiple sites during the first week after birth.
      Clinicians, health-care organizations, parents, and payors and purchasers of
      health care were often unaware of the ongoing patterns of care that may have
      obstructed preventive care. Now, partly based on these analyses, key
      recommendations have led to clinical usable guidelines for practitioners and have
      contributed to systems-oriented national guidelines for evidence-based safer
      management of newborn jaundice.(1) Clinician- and family-oriented tool kits have
      been made available, based on the report presented in this study, to facilitate
      effective implementation and thus optimize and institutionalize these guidelines
      (http://www.cdc.gov/jaundice). An informed partnership of parents and clinicians
      seems to be the most effective strategy to prevent severe neonatal
      hyperbilirubinemia and 'near-miss' cases of kernicterus in the United States.

PMID- 19177059
TI  - The need for neonatal glucose-6-phosphate dehydrogenase screening: a global
      perspective.
AB  - Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is an important cause of
      severe neonatal hyperbilirubinemia, and is overrepresented, even in countries
      with a low overall incidence of the enzyme deficiency, in the etiology of
      kernicterus. Neonatal screening for G-6-PD deficiency before discharge from the
      birth hospitalization should be instrumental in increasing parental and medical
      caretaker awareness of the high-risk nature of an infant, thereby effecting
      earlier referral of hyperbilirubinemic neonates for medical evaluation and
      treatment. The need for global screening, timing of screening, and the pros and
      cons of biochemical versus molecular DNA screening were discussed at the Newborn
      Jaundice and Kernicterus Meeting in Siena. The participants agreed that there was
      a need to expand neonatal G-6-PD screening globally and that screening results
      should be obtained before the infants' discharge from birth hospitalization.

PMID- 19177060
TI  - Systems changes to prevent severe hyperbilirubinemia and promote breastfeeding:
      pilot approaches.
AB  - Providing safe and effective care requires coordination among the multiple levels
      of the health care system. These levels comprise the newborn (patient, family and
      community), nursery or primary care practice (microsystem), hospital or managed
      care organization (macro-organization) and policy, payment or regulatory issues
      (environmental context). Contemporary care practices associated with childbirth
      and early newborn care often reflect disruptions in coordination of these
      processes and place newborns at risk for poor outcomes. For example, with routine
      early postpartum discharge, often at less than 48 h after vaginal birth, the peak
      of serum bilirubin at 3 to 5 days of age typically occurs at home, rather than
      observed by clinicians in a newborn nursery. In addition, lactation is rarely
      well established by early discharge and support is often inadequate, increasing
      the risk of hyperbilirubinemia and discontinuation of breastfeeding. Also, late
      preterm infants are frequently cared for in the newborn nursery, although they
      often have difficulty establishing oral feeding and are at substantially higher
      risk for severe hyperbilirubinemia than infants born at term. Finally, pediatric
      follow-up is often delayed beyond the first week, after the optimal time for
      continued assessment of jaundice and lactation. The American Academy of
      Pediatrics Safe and Healthy Beginnings Initiative, a pilot quality improvement
      project, will target newborn nurseries, primary care practices and coordination
      between these sites using a systems-based approach to facilitate implementation
      of the 2004 guideline for management of hyperbilirubinemia.

PMID- 19177061
TI  - Neonatal hyperbilirubinemia management: a model for change.
AB  - Currently, active public health surveillance of hyperbilirubinemia and
      kernicterus is lacking. Recently, the Hospital Corporation of America (HCA), a
      private health care system with an estimated quarter of a million births
      annually, instituted recommendations to provide universal hyperbilirubinemia
      screening before discharge for all infants born within their system. Over 98% of
      the infants born at HCA hospitals were screened within the first year of the
      recommendations. From May to December 2004, 13 infants were identified with total
      serum bilirubin (TSB) >/=30 mg per 100 ml, but that number was reduced in 2006,
      with only seven infants born in HCA hospitals developing a TSB of >/=30 mg per
      100 ml. This program provides a model for actively monitoring the occurrence of
      hyperbilirubinemia and for tracking its occurrence, thus improving health care
      quality for patients while collecting important public health information.

PMID- 19177062
TI  - A proposal to prevent severe neonatal hyperbilirubinemia and kernicterus.
AB  - To address systems failures and promote a safer management of newborn jaundice,
      we propose an 'aviation safety standard' for newborn health-care services during
      the first week after birth. Systems failure in newborn jaundice management has
      been characterized by lapses in concern, loss of continuity, and delays in care
      by multiple providers at multiple sites. Components for a six-step national
      strategy to prevent severe neonatal hyperbilirubinemia and possibly kernicterus
      are being implemented as delineated in the 2004 AAP guidelines. The clinical
      guidelines for safer and evidence-based practice have been characterized by both
      healthcare and societal communities. Professional and community organizations are
      optimizing outreach resources and facilitating institutionalization of these
      practices. Nationwide implementation at individual birthing hospitals concurrent
      with surveillance feedback needs to be initiated. Implementation of a 'six-sigma'
      approach, as proposed to the current Center for Disease Control and Prevention
      initiated partnership (health-care providers, public health and community
      advocates) may be achieved through collaboration with state and national
      agencies.

PMID- 19177063
TI  - Biological risks for neurological abnormalities associated with
      hyperbilirubinemia.
AB  - Unconjugated bilirubin (UCB) injury to glial cells leads to the secretion of
      glutamate and elicits a typical inflammatory response. Release of pro
      inflammatory cytokines may influence gliogenesis and neurogenesis, and lead to
      deficits in learning and memory. Glutamate metabolism dysregulation and
      overexpression of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)
      1beta are consistent with schizophrenia neuropathology. Recently, an increased
      prevalence of schizophrenia was reported in individuals with Gilbert's syndrome
      and among those who have had elevated levels of UCB in the neonatal life. In this
      review, we explore the reactivity of astrocytes, neurons and microglia to UCB,
      the cascade of events implicated in the immunostimulant effects of UCB, as well
      as the role of each nerve cell type and maturation state in the neuropathology of
      UCB. Identification of the signaling events promoted by UCB will be relevant for
      developing novel therapies that might reduce the risk of brain injury and
      disabilities.

PMID- 19177065
TI  - Safety assessment and dose selection for first-in-human clinical trials with
      immunomodulatory monoclonal antibodies.
AB  - Modulating immune responses with monoclonal antibodies (mAbs) that target immune
      molecules has become a promising therapeutic strategy and is under investigation
      for the treatment of cancer and (auto)-immune diseases. A major hurdle to the
      development and early clinical investigation of many immunomodulatory mAbs is the
      inherent risk of adverse immune-mediated drug reactions in humans, such as
      cytokine storms, autoimmunity, and immunosuppression. Dose selection for first-in
      human (FIH) clinical trials involving immunomodulatory mAbs, and mAbs in general,
      is based on specifically designed preclinical safety studies, primarily in
      nonhuman primates (NHPs), and on mechanistic ex vivo investigations. Dose
      selection in such trials is challenging for a number of reasons related to
      safety. In this context, safety-relevant differences between NHP and human immune
      systems, species selection/qualification and preclinical study design
      considerations, the receptor occupancy model and its calculation, the minimal
      anticipated biological effect level (MABEL) and its use in the selection of a
      safe starting dose in humans, microdosing and the impact of immunogenicity on
      safety assessment of mAbs, and safety-relevant formulation properties of
      therapeutic mAbs are critically reviewed. In addition, the current regulatory
      requirements are presented and discussed to demonstrate how the TeGenero TGN1412
      case is leading to increased regulatory scrutiny regarding dose selection for FIH
      clinical trials.

PMID- 19177064
TI  - Data-driven methods to discover molecular determinants of serious adverse drug
      events.
AB  - The dangers of serious adverse drug reactions (SADRs) are well known to
      clinicians, pharmacologists, and the lay public. Efforts to elucidate the
      molecular mechanisms behind SADRs have made significant progress through genetics
      and gene expression measurements. However, as the field of pharmacology adopts
      the same novel higher-density measurement modalities that have proven successful
      in other areas of biology, one wonders whether there can be more ways to benefit
      from the explosion of data created by these tools. The development of analytic
      tools and algorithms to interpret these biological data to create tools for
      medicine is central to the field of translational bioinformatics. In this review
      we introduce some of the types of SADR predictors that are required, and we
      discuss several databases that are publicly available for the study of SADRs,
      ranging from clinical to molecular measurements. We also describe recent examples
      of how bioinformatics methods coupled with data repositories can advance the
      science of SADRs.

PMID- 19177066
TI  - Enhanced sensitivity of the MRL/MpJ mouse to the neuroplastic and behavioral
      effects of chronic antidepressant treatments.
AB  - Chronic administration of antidepressant drugs produce changes in neuroplasticity
      and behavior in rodents, effects that may be associated with the slow emergence
      of clinical therapeutic effects. Owing to the uncertainty over the effects of
      chronic antidepressant treatments in mice, these experiments compared the
      regulation of neurogenesis, neurotrophin levels, and behavior produced by chronic
      antidepressant treatments between two inbred mouse strains, MRL/MpJ and C57BL/6J.
      The MRL/MpJ strain is associated with enhanced wound healing and tissue
      regeneration, whereas C57BL/6J mice are used commonly for behavioral studies.
      Proliferation and survival of hippocampal progenitor cells were measured using
      flow cytometry, a new platform that rapidly quantifies the incorporation of 5
      bromo-2-deoxyuridine (BrdU). Hippocampal cell proliferation was increased
      significantly after chronic administration of fluoxetine (FLX: 5, 10 mg/kg,
      intraperitoneal (i.p.), b.i.d.) or desipramine (DMI: 5, 10 mg/kg, i.p., b.i.d.)
      for 21 days in MRL/MpJ mice, but not in C57BL/6J mice. Hippocampal progenitor
      cells born prior to chronic antidepressant treatments were not affected in either
      mouse strain. Protein levels of brain-derived neurotrophic factor (BDNF) in
      MRL/MpJ mice were elevated significantly in the frontal cortex, hippocampus, and
      amygdala after chronic FLX treatment, but increased only in the frontal cortex by
      chronic DMI. In contrast, BDNF levels in C57BL/6J mice were decreased in the
      hippocampus and increased in the amygdala after chronic FLX, and were decreased
      in the brain stem after chronic DMI. Novelty-induced hypophagia (NIH) was used to
      examine a behavioral effect produced by chronic antidepressant treatment. MRL/MpJ
      mice, chronically administered FLX or DMI, had significantly shorter latencies to
      consume food when exposed to a novel environment than untreated mice, whereas
      there were no effects on the behavior of C57BL/6J mice. In conclusion, robust
      effects of chronic antidepressant treatments on hippocampal cell proliferation
      and BDNF levels paralleled the ability of these drugs to produce changes in NIH
      behavior in MRL/MpJ, while none of these effects were produced in C57BL/6J mice.
      The greater responsiveness of MRL/MpJ mice may be important for drug discovery,
      for genetic studies, and for understanding the neural mechanisms underlying the
      physiological and behavioral effects of chronic antidepressant treatments.

PMID- 19177068
TI  - Overstated conclusions and overstretched diagnosis?

PMID- 19177067
TI  - Dopamine D1 receptors in cocaine dependence measured with PET and the choice to
      self-administer cocaine.
AB  - The goal of this study was to determine D(1) receptor availability in human
      cocaine-dependent (CD) subjects and matched healthy controls (HCs). In addition,
      the CD subjects performed cocaine self-administration sessions in order to
      explore the association between D(1) receptor availability and cocaine-seeking
      behavior. Twenty-five CD subjects (40+/-4 years, 19M/6 F) and 23 matched HCs
      (38+/-4 years, 19M/4F) were scanned with PET and the radiotracer [(11)C]NNC 112.
      During the cocaine self-administration sessions, CD volunteers were given the
      choice to self-administer cocaine (0, 6, and 12 mg) or to receive a monetary
      voucher worth $5. D(1) receptor availability was measured in the limbic,
      associative, and sensori-motor striatum in addition to cortical brain regions. No
      difference in D(1) receptor availability was seen between the two groups. A
      negative association was seen between D(1) receptor BP(ND) in the limbic striatum
      and the choice for the 6 mg dose of cocaine (r=-0.47, p=0.02, corrected for age).
      These results do not support the hypothesis that cocaine dependence is associated
      with a reduction in D(1) receptor availability in the striatum. However, within
      the CD subjects, low D(1) receptor availability in the ventral striatum was
      associated with the choice to self-administer cocaine, suggesting that low D(1)
      receptor availability may be associated with an increased risk of relapse in
      cocaine dependence.

PMID- 19177069
TI  - Does albumin resuscitation have a role in the early prevention of sepsis
      associated acute kidney injury?

PMID- 19177073
TI  - Science restored.

PMID- 19177074
TI  - An appeal to President Ahmadinejad.

PMID- 19177075
TI  - A responsibility index.

PMID- 19177083
TI  - Journal club. An organic chemist highlights an ingenious way to make
      radiotracers.

PMID- 19177087
TI  - Stem cells ready for prime time.

PMID- 19177088
TI  - Iranian AIDS doctors' trial draws condemnation.

PMID- 19177089
TI  - Laser facility flickers into life.

PMID- 19177090
TI  - Cutting out the chemicals.

PMID- 19177091
TI  - Pfizer to buy Wyeth in $68-billion deal.

PMID- 19177092
TI  - Ocean fertilization: dead in the water?

PMID- 19177093
TI  - Science adviser should show his independence, says report.

PMID- 19177094
TI  - China targets top talent from overseas.

PMID- 19177102
TI  - Neuroscience: Making connections.

PMID- 19177103
TI  - Behavioural science: secret signals.

PMID- 19177104
TI  - A medical view of potential adverse effects.

PMID- 19177105
TI  - Much ado about cognitive enhancement.

PMID- 19177106
TI  - Risks and benefits may turn out to be finely balanced.

PMID- 19177107
TI  - Enhancement means a broader role for physicians.

PMID- 19177108
TI  - Careful use helps me do better research, and society benefits.

PMID- 19177109
TI  - Recall of learned information may rely on taking drug again.

PMID- 19177110
TI  - Patterns of drug use have varied throughout history.

PMID- 19177111
TI  - Pruning the regulatory tree.

PMID- 19177112
TI  - Accelerating production of medical isotopes.

PMID- 19177117
TI  - Evolutionary genomics: A positive becomes a negative.

PMID- 19177118
TI  - Immunology: Natural killer cells remember.

PMID- 19177120
TI  - Condensed-matter physics: The pnictide code.

PMID- 19177121
TI  - Plant genomics: Sorghum in sequence.

PMID- 19177123
TI  - Evolutionary genetics: Origins of reproductive isolation.

PMID- 19177122
TI  - Organic chemistry: Chlorine lends a helping hand.

PMID- 19177124
TI  - Rapid heating of the atmosphere of an extrasolar planet.
AB  - Near-infrared observations of more than a dozen 'hot-Jupiter' extrasolar planets
      have now been reported. These planets display a wide diversity of properties, yet
      all are believed to have had their spin periods tidally spin-synchronized with
      their orbital periods, resulting in permanent star-facing hemispheres and surface
      flow patterns that are most likely in equilibrium. Planets in significantly
      eccentric orbits can enable direct measurements of global heating that are
      largely independent of the details of the hydrodynamic flow. Here we report 8
      microm photometric observations of the planet HD 80606b during a 30-hour interval
      bracketing the periastron passage of its extremely eccentric 111.4-day orbit. As
      the planet received its strongest irradiation (828 times larger than the flux
      received at apastron) its maximum 8-microm brightness temperature increased from
      approximately 800 K to approximately 1,500 K over a six-hour period. We also
      detected a secondary eclipse for the planet, which implies an orbital inclination
      of i approximately 90 degrees , fixes the planetary mass at four times the mass
      of Jupiter, and constrains the planet's tidal luminosity. Our measurement of the
      global heating rate indicates that the radiative time constant at the planet's 8
      microm photosphere is approximately 4.5 h, in comparison with 3-5 days in Earth's
      stratosphere.

PMID- 19177125
TI  - Nearly isotropic superconductivity in (Ba,K)Fe(2)As(2).
AB  - Superconductivity was recently observed in iron-arsenic-based compounds with a
      superconducting transition temperature (T(c)) as high as 56 K, naturally raising
      comparisons with the high-T(c) copper oxides. The copper oxides have layered
      crystal structures with quasi-two-dimensional electronic properties, which led to
      speculation that reduced dimensionality (that is, extreme anisotropy) is a
      necessary prerequisite for superconductivity at temperatures above 40 K (refs 8,
      9). Early work on the iron-arsenic compounds seemed to support this view. Here we
      report measurements of the electrical resistivity in single crystals of
      (Ba,K)Fe(2)As(2) in a magnetic field up to 60 T. We find that the superconducting
      properties are in fact quite isotropic, being rather independent of the direction
      of the applied magnetic fields at low temperature. Such behaviour is strikingly
      different from all previously known layered superconductors, and indicates that
      reduced dimensionality in these compounds is not a prerequisite for 'high
      temperature' superconductivity. We suggest that this situation arises because of
      the underlying electronic structure of the iron-arsenic compounds, which appears
      to be much more three dimensional than that of the copper oxides. Extrapolations
      of low-field single-crystal data incorrectly suggest a high anisotropy and a
      greatly exaggerated zero-temperature upper critical field.

PMID- 19177126
TI  - (pi, pi) electronic order in iron arsenide superconductors.
AB  - The distribution of valence electrons in metals usually follows the symmetry of
      the underlying ionic lattice. Modulations of this distribution often occur when
      those electrons are not stable with respect to a new electronic order, such as
      spin or charge density waves. Electron density waves have been observed in many
      families of superconductors, and are often considered to be essential for
      superconductivity to exist. Recent measurements seem to show that the properties
      of the iron pnictides are in good agreement with band structure calculations that
      do not include additional ordering, implying no relation between density waves
      and superconductivity in these materials. Here we report that the electronic
      structure of Ba(1-x)K(x)Fe(2)As(2) is in sharp disagreement with those band
      structure calculations, and instead reveals a reconstruction characterized by a
      (pi, pi) wavevector. This electronic order coexists with superconductivity and
      persists up to room temperature (300 K).

PMID- 19177127
TI  - Total synthesis of a chlorosulpholipid cytotoxin associated with seafood
      poisoning.
AB  - Each year, there are many cases of seafood poisoning in humans worldwide. Among
      the various toxins isolated that contribute to these poisonings, the
      chlorosulpholipids are particularly intriguing because of their structural and
      stereochemical complexity. The mechanism of biological activity remains unknown
      and, although chlorosulpholipids are associated with membranes in the organisms
      from which they are isolated, little is understood about their role within
      biological membranes. The lack of availability of the natural products has
      impaired more in-depth biochemical studies. So far, none of the
      chlorosulpholipids have been obtained from total synthesis, and efficient routes
      to their synthesis would be desirable for the preparation of material for
      pharmacological characterization and proper evaluation of the risk to human
      health. Despite the notable advances in the science of organic synthesis,
      reliable methods for stereoselective construction of polychlorinated acyclic
      substrates are lacking, although some preliminary investigations have appeared.
      Here we report the synthesis of a chlorosulpholipid cytotoxin, leading to
      confirmation of the proposed structure and the discovery of unanticipated
      reactivity of polychlorinated hydrocarbons. The concise synthetic approach should
      enable the preparation of material in sufficient quantities to facilitate
      biological studies.

PMID- 19177128
TI  - Southern Ocean deep-water carbon export enhanced by natural iron fertilization.
AB  - The addition of iron to high-nutrient, low-chlorophyll regions induces
      phytoplankton blooms that take up carbon. Carbon export from the surface layer
      and, in particular, the ability of the ocean and sediments to sequester carbon
      for many years remains, however, poorly quantified. Here we report data from the
      CROZEX experiment in the Southern Ocean, which was conducted to test the
      hypothesis that the observed north-south gradient in phytoplankton concentrations
      in the vicinity of the Crozet Islands is induced by natural iron fertilization
      that results in enhanced organic carbon flux to the deep ocean. We report annual
      particulate carbon fluxes out of the surface layer, at three kilometres below the
      ocean surface and to the ocean floor. We find that carbon fluxes from a highly
      productive, naturally iron-fertilized region of the sub-Antarctic Southern Ocean
      are two to three times larger than the carbon fluxes from an adjacent high
      nutrient, low-chlorophyll area not fertilized by iron. Our findings support the
      hypothesis that increased iron supply to the glacial sub-Antarctic may have
      directly enhanced carbon export to the deep ocean. The CROZEX sequestration
      efficiency (the amount of carbon sequestered below the depth of winter mixing for
      a given iron supply) of 8,600 mol mol(-1) was 18 times greater than that of a
      phytoplankton bloom induced artificially by adding iron, but 77 times smaller
      than that of another bloom initiated, like CROZEX, by a natural supply of iron.
      Large losses of purposefully added iron can explain the lower efficiency of the
      induced bloom(6). The discrepancy between the blooms naturally supplied with iron
      may result in part from an underestimate of horizontal iron supply.

PMID- 19177129
TI  - Glycobiology: A spoonful of sugar.

PMID- 19177133
TI  - Bacterial delivery of a novel cytolysin to hypoxic areas of solid tumors.
AB  - The efficacy of current anti-cancer gene therapies is limited by the inability of
      gene vectors to penetrate the poorly vascularized, hypoxic regions of tumors,
      leaving these sites untreated. We describe a new approach for targeting gene
      therapy to these sites, which employs an attenuated strain of the non-pathogenic
      bacterium, Salmonella typhimurium, carrying an exogenous (that is, reporter or
      therapeutic) gene under the regulation of a new, highly hypoxia-inducible
      promoter (FF+20(*)). This bacterial vector was seen to rapidly migrate into, and
      thrive in, hypoxic areas of both mammary tumor spheroids grown in vitro and
      orthotopic mammary tumors after systemic injection. Using the reporter gene
      construct, FF+20(*)-lacZ, we show that bacterial expression of high levels of
      beta-galactosidase occurred only in hypoxic/necrotic sites of spheroids and
      tumors. We then replaced the reporter gene with one encoding a novel cytotoxic
      protein (HlyE) and showed that this was also expressed by bacteria only in
      hypoxic regions of murine mammary tumors. This resulted in a marked increase in
      tumor necrosis and reduced tumor growth. Our system represents a promising new
      strategy for delivering gene therapy to poorly vascularized regions of tumors and
      shows, for the first time, the efficacy of HlyE as an anti-tumor agent.

PMID- 19177134
TI  - Integration of functional bacterial artificial chromosomes into human cord blood
      derived multipotent stem cells.
AB  - Stem cells from a patient with a genetic disease could be used for cell therapy
      if it were possible to insert a functional copy of the defective gene. In this
      study, we investigate the transfection and subsequent integration of large
      genomic fragments into human cord blood-derived multipotent stem cells. We
      describe for the first time the creation of clonal stem cells carrying a human
      bacterial artificial chromosome (BAC) containing the Friedreich ataxia locus with
      an enhanced green fluorescent protein (EGFP) reporter gene fused to exon 5a of
      the frataxin (FXN) gene. Integration of the BAC into the host cell genome was
      confirmed by PCR, Southern blot and fluorescent in situ hybridization analysis.
      Reverse transcription-PCR and flow cytometry confirmed expression of FXN-EGFP.
      Correct mitochondrial localization of the protein was confirmed using fluorescent
      microscopy. The transfected stem cells also retained the ability to differentiate
      into cells from all three germline layers, as demonstrated by the capacity to
      form neuron-specific beta-tubulin-expressing cells, Alizarin Red S-positive bone
      like cells, and epithelial-like cells expressing surfactant protein C. This is
      the first study to demonstrate that cord blood-derived multipotent stem cells may
      be useful targets for gene therapy applications using large genomic loci.

PMID- 19177136
TI  - Sensitivity and specificity of multiphoton laser tomography for in vivo and ex
      vivo diagnosis of malignant melanoma.
AB  - The incidence of malignant melanoma has shown a dramatic increase over the past
      three decades. Patient outcome and curability depend on early diagnosis. In vivo
      multiphoton laser tomography represents a recently developed diagnostic tool that
      allows non-invasive tissue imaging. We aim to demonstrate the application of
      multiphoton laser tomography for the in vivo differentiation and diagnosis of
      melanoma. Laser radiation in the near infrared spectrum was used to image
      endogenous fluorophores by multiphoton excitation. Eighty-three melanocytic skin
      lesions have been investigated. The results showed distinct morphological
      differences in melanoma compared with melanocytic nevi. In particular, six
      characteristic features of malignant melanoma were specified and statistically
      evaluated. Sensitivity values up to 95% (range: 71-95%) and specificity values up
      to 97% (range: 69-97%) were achieved for diagnostic classification. Logistic
      regression analysis was performed to identify the most significant diagnostic
      criteria. We found that architectural disarray of the epidermis, poorly defined
      keratinocyte cell borders as well as the presence of pleomorphic or dendritic
      cells were of prime importance. By means of this procedure accuracy values up to
      97% were reached. These findings underline the potential applicability of
      multiphoton laser tomography in melanoma diagnosis of melanocytic skin lesions.

PMID- 19177137
TI  - pH-regulated mechanisms account for pigment-type differences in epidermal barrier
      function.
AB  - To determine whether pigment type determines differences in epidermal function,
      we studied stratum corneum (SC) pH, permeability barrier homeostasis, and SC
      integrity in three geographically disparate populations with pigment type I-II
      versus IV-V skin (Fitzpatrick I-VI scale). Type IV-V subjects showed: (i) lower
      surface pH (approximately 0.5 U); (ii) enhanced SC integrity (transepidermal
      water loss change with sequential tape strippings); and (iii) more rapid barrier
      recovery than type I-II subjects. Enhanced barrier function could be ascribed to
      increased epidermal lipid content, increased lamellar body production, and
      reduced acidity, leading to enhanced lipid processing. Compromised SC integrity
      in type I-II subjects could be ascribed to increased serine protease activity,
      resulting in accelerated desmoglein-1 (DSG-1)/corneodesmosome degradation. In
      contrast, DSG-1-positive CDs persisted in type IV-V subjects, but due to enhanced
      cathepsin-D activity, SC thickness did not increase. Adjustment of pH of type I
      II SC to type IV-V levels improved epidermal function. Finally, dendrites from
      type IV-V melanocytes were more acidic than those from type I-II subjects, and
      they transfer more melanosomes to the SC, suggesting that melanosome secretion
      could contribute to the more acidic pH of type IV-V skin. These studies show
      marked pigment-type differences in epidermal structure and function that are pH
      driven.

PMID- 19177135
TI  - A Wnt survival guide: from flies to human disease.
AB  - It has been two decades since investigators discovered the link between the
      Drosophila wingless (Wg) gene and the vertebrate oncogene int-1, thus
      establishing the family of signaling proteins known as Wnts. Since the inception
      of the Wnt signaling field, there have been 19 Wnt isoforms identified in humans.
      These secreted glycoproteins can activate at least two distinct signaling
      pathways in vertebrate cells, leading to cellular changes that regulate a vast
      array of biological processes, including embryonic development, cell fate, cell
      proliferation, cell migration, stem cell maintenance, tumor suppression, and
      oncogenesis. In certain contexts, one subset of Wnt isoforms activates the
      canonical Wnt/beta-catenin pathway that is characterized by the activation of
      certain beta-catenin-responsive target genes in response to the binding of Wnt
      ligand to its cognate receptors. Similarly, a second subset of Wnt isoforms
      activates beta-catenin-independent pathways, including the Wnt/calcium (Wnt/Ca)
      pathway and the Wnt/planar cell polarity (Wnt/PCP) pathway, in certain cellular
      contexts. In addition, research has identified several secreted proteins known to
      regulate Wnt signaling, including the Dickkopf (DKK) family, secreted Frizzled
      related proteins (sFRPs), and Wnt inhibitory factor-1 (WIF-1). The advent of
      technologies that can provide genome-wide expression data continues to implicate
      Wnts and proteins that regulate Wnt signaling pathways in a growing number of
      disease processes. The aim of this review is to provide a context on the Wnt
      field that will facilitate the interpretation and study of Wnt signaling in the
      context of human disease.

PMID- 19177138
TI  - P-selectin glycoprotein ligand-1 contributes to wound healing predominantly as a
      p-selectin ligand and partly as an e-selectin ligand.
AB  - Cell adhesion molecules are critical to wound healing through leukocyte
      recruitment. Although P-selectin glycoprotein ligand-1 (PSGL-1) regulates
      leukocyte rolling by binding P-selectin, but also binding E- and L-selectins with
      lower affinity, little is known about a role of PSGL-1 in wound healing. To
      clarify a role of PSGL-1 and its interaction with E- and P-selectins in wound
      healing, we investigated cutaneous wound healing in PSGL-1-deficient (PSGL-1(-/
      )) mice in comparison with E-selectin(-/-), P-selectin(-/-), and P-selectin(-/-)
      mice treated with an anti-E-selectin antibody. PSGL-1 deficiency inhibited early
      wound healing, which was accompanied by decreased inflammatory cell infiltration
      and growth factor expression. By contrast, E-selectin deficiency did not affect
      wound healing. In general, the inhibitory effect of PSGL-1 deficiency on wound
      healing was similar to that of P-selectin deficiency either alone or with E
      selectin blockade. However, early granulation tissue formation, late
      angiogenesis, and early infiltration of neutrophils and macrophages in PSGL-1(-/
      ) mice were inhibited beyond the inhibition in P-selectin(-/-) mice, but to a
      similar level of inhibition in P-selectin(-/-) mice with E-selectin blockade.
      These results suggest that PSGL-1 contributes to wound healing predominantly as a
      P-selectin ligand and partly as an E-selectin ligand by mediating infiltration of
      inflammatory cells.

PMID- 19177139
TI  - Maintenance of an acidic stratum corneum prevents emergence of murine atopic
      dermatitis.
AB  - Neutralization of stratum corneum (SC) adversely impacts key epidermal functions,
      including permeability barrier homeostasis and SC integrity. Conversely,
      acidification of SC improves these functions in developmentally impaired
      (neonatal or aged) skin, and enhances function in normal skin. Hence, we
      hypothesized that acidification could alter the course of inflammatory
      dermatoses, which invariably exhibit an increased SC pH. Maintenance of a low pH
      by topical applications of the polyhydroxyl acid, lactobionic acid, during the
      repeated-challenge phase inhibited the development of oxazolone-induced atopic
      dermatitis (AD). Neither gross/histological dermatitis nor altered barrier
      function developed, and emergence of epidermal hyperplasia was prevented;
      however, cytokine generation decreased. Acidification also largely normalized the
      development of hapten-induced changes in eosinophil/mast cell densities, density
      of chemoattractant receptor-homologous molecule expressed on TH2-positive
      lymphocytes, and serum IgE levels. The pH-induced improvement in barrier function
      most likely accounts for the anti-inflammatory activity, which could be further
      attributed to normalization of both lamellar body secretion and lamellar bilayer
      formation. Acidification of SC alone substantially prevents development of
      barrier abnormalities and downstream immune abnormalities during the elicitation
      phase of murine AD. These results provide direct evidence for the "outside
      inside" pathogenesis of AD and further suggest that maintenance of an acidic SC
      pH could prevent the emergence of AD in humans.

PMID- 19177140
TI  - The localization of label-retaining cells in eccrine glands.

PMID- 19177142
TI  - In vitro and in vivo anti-melanoma effects of ciglitazone.
AB  - Activation of PPARgamma by synthetic ligands, thiazolidinediones, inhibits the
      proliferation of cancer cells. In this report, focusing our attention on
      ciglitazone, we show that ciglitazone inhibits melanoma growth by inducing
      apoptosis and cell-cycle arrest, whereas normal melanocytes are resistant to
      ciglitazone. In melanoma cells, ciglitazone-induced apoptosis is associated with
      caspase activations and a loss of mitochondrial membrane potential. Induction of
      cell-cycle arrest by ciglitazone is associated with changes in expression of key
      cell-cycle regulators such as p21, cyclin D1, and pRB hypophosphorylation. Cell
      cycle arrest occurs at low ciglitazone concentrations and through a PPARgamma
      dependent pathway, whereas the induction of apoptosis is caused by higher
      ciglitazone concentrations and independently of PPARgamma. These results allow an
      effective molecular dissociation between proapoptotic effects and growth
      inhibition evoked by ciglitazone in melanoma cells. Finally, we show that in vivo
      treatment of nude mice by ciglitazone dramatically inhibits human melanoma
      xenograft development. The data presented suggest that ciglitazone might be a
      better candidate for clinical trials in melanoma treatment than the
      thiazolidinediones currently used in the treatment of type 2 diabetes, such as
      rosiglitazone, which is devoid of a proapoptotic PPARgamma-independent function.

PMID- 19177141
TI  - A comparison of two regimens of topical corticosteroids in the treatment of
      patients with bullous pemphigoid: a multicenter randomized study.
AB  - Superpotent topical corticosteroids (CS) have been demonstrated to improve
      bullous pemphigoid (BP) patients' survival. We assessed whether a mild regimen
      using lower doses of topical CS and a shorter duration could improve the outcome
      of BP patients even more. Three-hundred and twelve BP patients were included in a
      multicenter randomized controlled trial and stratified depending on the extent of
      BP as moderate (n=134) or extensive (n=178). Patients were randomly assigned to
      the standard regimen (clobetasol propionate cream, 40 g per day initially, with
      CS tapering over 12 months) or the mild regimen (10-30 g per day), with CS
      tapering over 4 months. A noninferior rate of BP control was obtained with the
      mild regimen 156/159 (98%) as compared with the standard regimen 150/150 (100%;
      P=0.005). Event-free survival, that is, the combined outcome of deaths and life
      threatening adverse events did not differ between the two treatment groups
      (P=0.77). However, upon adjusting through the Cox model for age and Karnofsky
      score, a strong beneficial effect of the mild regimen was observed in patients
      with moderate BP, with an almost twofold decrease in the risk of death or life
      threatening adverse events relative to the standard regimen (hazard ratio=0.54;
      95% confidence interval, 0.30-0.97; P=0.039). This mild regimen allows a 70%
      reduction of the cumulative doses of CS and improves BP patients' outcome.

PMID- 19177143
TI  - Wnt5A activates the calpain-mediated cleavage of filamin A.
AB  - We have previously shown that Wnt5A and ROR2, an orphan tyrosine kinase receptor,
      interact to mediate melanoma cell motility. In other cell types, this can occur
      through the interaction of ROR2 with the cytoskeletal protein filamin A. Here, we
      found that filamin A protein levels correlated with Wnt5A levels in melanoma
      cells. Small interfering RNA (siRNA) knockdown of WNT5A decreased filamin A
      expression. Knockdown of filamin A also corresponded to a decrease in melanoma
      cell motility. In metastatic cells, filamin A expression was predominant in the
      cytoplasm, which western analysis indicated was due to the cleavage of filamin A
      in these cells. Treatment of nonmetastatic melanoma cells with recombinant Wnt5A
      increased filamin A cleavage, and this could be prevented by the knockdown of
      ROR2 expression. Further, BAPTA-AM chelation of intracellular calcium also
      inhibited filamin A cleavage, leading to the hypothesis that Wnt5A/ROR2 signaling
      could cleave filamin A through activation of calcium-activated proteases, such as
      calpains. Indeed, WNT5A knockdown decreased calpain 1 expression, and by
      inhibiting calpain 1 either pharmacologically or using siRNA, it decreased cell
      motility. Our results indicate that Wnt5A activates calpain-1, leading to the
      cleavage of filamin A, which results in a remodeling of the cytoskeleton and an
      increase in melanoma cell motility.

PMID- 19177144
TI  - IgG from patients with bullous pemphigoid depletes cultured keratinocytes of the
      180-kDa bullous pemphigoid antigen (type XVII collagen) and weakens cell
      attachment.
AB  - We have shown that binding of bullous pemphigoid (BP)-patient IgG (BP-IgG) causes
      the internalization of BP180 from the cell membrane. This study examined whether
      BP-IgG treatment can deplete cultured keratinocytes of BP180, how it affects
      cellular levels of alpha6 and beta4 integrins (by western blot analysis using
      monoclonal antibodies to these antigens), and whether it reduces adhesion of
      cells to the culture dish (by a vibration detachment assay). All BP-IgG or BP
      sera with high values of BP180-ELISA from 18 BP patients before and after oral
      corticosteroid treatment showed dramatically decreased BP180 in cells after 6
      hours of BP-IgG stimulation, whereas alpha6 and beta4 integrin levels were not
      decreased. Even IgG from patients in whom oral corticosteroid had suppressed
      active blistering could deplete cells of BP180, as long as sera retained a high
      value of BP180-ELISA. On the other hand, reduction of cell BP180 content
      increased detachment of cells from the dish. These results suggest that BP-IgG
      reduces hemidesmosomal BP180 content, weakening the adhesion of hemidesmosomes to
      the lamina densa. In the presence of BP180 deficiency, inflammation generated by
      BP180 immune-complex formation might then tear the weakened lamina lucida, and
      this could lead to generation of the BP-specific split at the lamina lucida.

PMID- 19177145
TI  - Suprabasal spongiosis in acute eczematous dermatitis: cFLIP maintains resistance
      of basal keratinocytes to T-cell-mediated apoptosis.
AB  - In acute eczematous dermatitis, keratinocyte (KC) apoptosis caused by dermis
      infiltrating, activated T cells plays a crucial pathogenetic role in the
      development of spongiosis, the histopathological hallmark of acute eczema.
      Remarkably, T-cell-mediated apoptosis of single KC, as well as spongiosis, is
      located predominantly in suprabasal epidermal layers, suggesting that
      antiapoptotic mechanisms protect basal KC. The cellular Flice-inhibitory protein
      (cFLIP) is known to block apoptotic CD95-signaling, and may therefore account for
      such a protection of basal KC. HaCaT KCs retrovirally transduced with the long
      form of cFLIP were effectively protected against T-cell-mediated apoptosis in KC
      monolayer/CD4(+) T-cell cocultures. In situ correlation of cFLIP protein
      expression and KC apoptosis in lesional eczematous skin showed a highly
      restricted expression of cFLIP in basal KC, whereas cleaved caspase-3 (as a
      surrogate marker of apoptosis) was detected predominantly in suprabasal epidermal
      layers. Thus, the modulation of the CD95 signaling pathway by the cell-intrinsic
      caspase-8 inhibitor cFLIP in basal KC may explain the spatial localization of
      spongiosis in suprabasal epidermal layers, and provides new insights into the
      pathogenesis of spongiosis formation in eczematous dermatitis.

PMID- 19177146
TI  - Identifying women most likely to benefit from prevention strategies for
      postpartum hemorrhage.
AB  - OBJECTIVE: To identify women who are most likely to benefit from primary
      prevention strategies for postpartum hemorrhage (PPH). STUDY DESIGN: In a
      retrospective patient cohort, we applied recursive partitioning algorithms to
      identify the most discriminant risk factors and their interactions, and
      calculated the 'number needed to treat' to prevent a single case of PPH
      (estimated blood loss >1000 ml). RESULT: By delivery category, the highest risk
      groups with 'number needed to treat' ranging from 4 to 7 were: (1) vaginal
      delivery (PPH=0.7% of 16 218)-macrosomia with gestational diabetes and manual
      removal of the placenta; (2) primary cesarean (PPH=18.7% of 2696)-macrosomia and
      multiparity; and (3) repeat cesarean (PPH=16.0% of 1832)-uterine incision other
      than low transverse and failed vaginal birth after cesarean. CONCLUSION: Clinical
      profiles that identify women at risk for PPH can provide a foundation for the
      development of primary prevention strategies.

PMID- 19177147
TI  - Surveillance of cardiovascular risk factors for outpatients in different erectile
      dysfunction severity.
AB  - We determined the association between the severity of erectile dysfunction (ED)
      and traditional cardiovascular risk factors, including metabolic syndrome (MS). A
      total of 141 ED patients were divided into three groups on the basis of ED
      severity, which was determined using the International Index of Erectile Function
      (IIEF) scores. The prevalence of MS among the ED patients was 32.6%.
      Significantly lower IIEF scores were noted in patients with MS than in patients
      without MS (7.6+/-6.4 vs 11.6+/-7.4, P=0.003). As assessed by the anthropometric
      indices of body mass index, waist circumference and waist-to-hip ratio, obesity
      was detected in 58.9, 54.6 and 32.6% of the patients, respectively. Of the 141
      patients, 39 had mild, 24 had moderate and 78 had severe ED. Statistically
      significant differences were noted among the different ED severity groups with
      regard to the presence of hypertension, systolic blood pressure, presence of MS
      and number of MS components. Multivariate analysis showed that the odds ratio for
      high-low-density lipoprotein (LDL) cholesterol level in moderate and severe ED,
      determined with reference to mild ED, were 9.346 and 6.452, respectively. The
      presence of MS, number of MS components, and certain traditional cardiovascular
      risk factors, particularly high-LDL cholesterol level and hypertension, may
      influence the severity of ED.

PMID- 19177148
TI  - Accumulation of raft lipids in T-cell plasma membrane domains engaged in TCR
      signalling.
AB  - Activating stimuli for T lymphocytes are transmitted through plasma membrane
      domains that form at T-cell antigen receptor (TCR) signalling foci. Here, we
      determined the molecular lipid composition of immunoisolated TCR activation
      domains. We observed that they accumulate cholesterol, sphingomyelin and
      saturated phosphatidylcholine species as compared with control plasma membrane
      fragments. This provides, for the first time, direct evidence that TCR activation
      domains comprise a distinct molecular lipid composition reminiscent of liquid
      ordered raft phases in model membranes. Interestingly, TCR activation domains
      were also enriched in plasmenyl phosphatidylethanolamine and phosphatidylserine.
      Modulating the T-cell lipidome with polyunsaturated fatty acids impaired the
      plasma membrane condensation at TCR signalling foci and resulted in a perturbed
      molecular lipid composition. These results correlate the accumulation of specific
      molecular lipid species with the specific plasma membrane condensation at sites
      of TCR activation and with early TCR activation responses.

PMID- 19177149
TI  - Dual DNA unwinding activities of the Rothmund-Thomson syndrome protein, RECQ4.
AB  - Human RECQ helicases have been linked to distinct clinical diseases with
      increased cancer rates and premature ageing. All RECQ proteins, except RECQ4,
      have been shown to be functional helicases. Mutations in RECQ4 lead to Rothmund
      Thomson syndrome (RTS), and mouse models reveal that the conserved helicase
      motifs are required for avoidance of RTS. Furthermore, the amino (N) terminus of
      RECQ4 shares homology with yeast DNA replication initiation factor, Sld2, and is
      vital for embryonic development. Here, in contrast to previous reports, we show
      that RECQ4 exhibits DNA helicase activity. Importantly, two distinct regions of
      the protein, the conserved helicase motifs and the Sld2-like N-terminal domain,
      each independently promote ATP-dependent DNA unwinding. Taken together, our data
      provide the first biochemical clues underlying the molecular function of RECQ4 in
      DNA replication and genome maintenance.

PMID- 19177151
TI  - A potential living kidney donor with prediabetes.

PMID- 19177152
TI  - Nephrology: a specialty in need of resuscitation?
AB  - Nephrology trainee recruitment is essential if we are to address the shortage of
      nephrologists in countries such as the USA, Canada, the UK and Australia. This
      Australian study determines barriers, following clinical exposure, to trainees'
      pursuing a career in nephrology.

PMID- 19177150
TI  - The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK
      ERK pathway to late endosomes.
AB  - The regulation of endosome dynamics is crucial for fundamental cellular
      functions, such as nutrient intake/digestion, membrane protein cycling, cell
      migration and intracellular signalling. Here, we show that a novel lipid raft
      adaptor protein, p18, is involved in controlling endosome dynamics by anchoring
      the MEK1-ERK pathway to late endosomes. p18 is anchored to lipid rafts of late
      endosomes through its N-terminal unique region. p18(-/-) mice are embryonic
      lethal and have severe defects in endosome/lysosome organization and membrane
      protein transport in the visceral endoderm. p18(-/-) cells exhibit apparent
      defects in endosome dynamics through perinuclear compartment, such as aberrant
      distribution and/or processing of lysosomes and impaired cycling of Rab11
      positive recycling endosomes. p18 specifically binds to the p14-MP1 complex, a
      scaffold for MEK1. Loss of p18 function excludes the p14-MP1 complex from late
      endosomes, resulting in a downregulation of the MEK-ERK activity. These results
      indicate that the lipid raft adaptor p18 is essential for anchoring the MEK-ERK
      pathway to late endosomes, and shed new light on a role of endosomal MEK-ERK
      pathway in controlling endosome dynamics.

PMID- 19177153
TI  - Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) are strongly
      associated with end-stage renal disease historically attributed to hypertension
      in African Americans.
AB  - African Americans have high incidence rates of end-stage renal disease (ESRD)
      labeled as due to hypertension. As recent studies showed strong association with
      idiopathic and HIV-related focal segmental glomerulosclerosis and non-muscle
      myosin heavy chain 9 (MYH9) gene polymorphisms in this ethnic group, we tested
      for MYH9 associations in a variety of kidney diseases. Fifteen MYH9 single
      nucleotide polymorphisms were evaluated in 175 African Americans with chronic
      glomerulonephritis-associated ESRD, 696 African Americans reportedly with
      hypertension-associated ESRD, and 948 control subjects without kidney disease.
      Significant associations were detected with 14 of the 15 polymorphisms in all 871
      non-diabetic patients with ESRD. In hypertension-associated ESRD cases alone,
      significant associations were found with 13 MYH9 polymorphisms and the previously
      reported E1 haplotype. Thus, hypertension-associated ESRD in African Americans is
      substantially related to MYH9 gene polymorphisms and this may explain the poor
      response to blood pressure control in those diagnosed with hypertensive
      nephrosclerosis. It is possible that many African Americans classified as having
      hypertension-associated ESRD have occult MYH9-associated segmental or global
      glomerulosclerosis. Our study shows that gene-environment and/or gene-gene
      interactions may initiate kidney disease in genetically susceptible individuals,
      because African Americans homozygous for MYH9 risk alleles do not universally
      develop kidney disease.

PMID- 19177154
TI  - For estimating creatinine clearance measuring muscle mass gives better results
      than those based on demographics.
AB  - Estimation of creatinine clearance requires knowledge of creatinine generation
      which can vary in different groups of patients. Since the main source of
      creatinine is muscle we used dual-energy X-ray absorptiometry to measure the mass
      of muscle in a cohort of adult men and women in Rochester, Minnesota. Serum and
      24 h urinary creatinines were measured directly. The urinary creatinine was
      estimated using equations based on age and gender and muscle mass in order to
      calculate creatinine clearance. Among 664 subjects with a mean age of 55+/-20
      years, 51% of whom were women, the model fit for urinary creatinine estimated
      with age and gender (R2=0.359) was similar to that estimated with measured muscle
      mass (R2=0.359). The likelihood of chronic kidney disease (creatinine clearance
      of less than 60 ml/min per 1.73 m2) in older subjects was highest with equations
      that used age, and likelihood of CKD in women was highest with equations that
      used gender. The outcomes of mortality and cardiovascular disease had stronger
      associations with decreased creatinine clearance calculated with age and gender
      than by the clearance calculated with muscle mass. This could be explained by age
      being a potent predictor of mortality and cardiovascular disease independent of
      urinary creatinine, muscle mass, and gender. Our study shows that the likelihood
      of chronic kidney disease in the elderly and in women and the risk of adverse
      outcomes may be inflated by equations that use patient demographics to estimate
      creatinine generation.

PMID- 19177155
TI  - Tacrolimus reduces nitric oxide synthase function by binding to FKBP rather than
      by its calcineurin effect.
AB  - Hypertension develops in many patients receiving the immunosuppressive drug
      tacrolimus (FK506). One possible mechanism for hypertension is a reduction in
      vasodilatory nitric oxide. We found that tacrolimus and a calcineurin
      autoinhibitory peptide significantly decreased vascular calcineurin activity;
      however, only tacrolimus altered intracellular calcium release in mouse aortic
      endothelial cells. In mouse aortas, incubation with tacrolimus increased protein
      kinase C activity and basal endothelial nitric oxide synthase phosphorylation at
      threonine 495 but reduced basal and agonist-induced endothelial nitric oxide
      synthase phosphorylation at serine 1177, a mechanism known to inhibit synthase
      activity. While this decreased nitric oxide production and endothelial function,
      the calcineurin autoinhibitory peptide had no such effects. Inhibition of
      ryanodine receptor opening or protein kinase C blocked the effects of tacrolimus.
      Since it is known that the FK506 binding protein (FKBP12/12.6) interacts with the
      ryanodine receptor to regulate calcium release, we propose this as the mechanism
      by which tacrolimus alters intracellular calcium and endothelial nitric oxide
      synthase rather than by its effect on calcineurin. Our study shows that
      prevention of the tacrolimus-induced intracellular calcium leak may attenuate
      endothelial dysfunction and the consequent hypertension.

PMID- 19177156
TI  - Insulin resistance and altered glucose transporter 4 expression in experimental
      uremia.
AB  - Progressive ventricular hypertrophy can lead to the development of insulin
      resistance, a feature of both chronic kidney disease and heart failure. Here we
      induced uremia in adult male Sprague-Dawley rats using a remnant kidney model and
      studied the expression of glucose transporters. As expected, the reduction of
      nephron mass resulted in impaired renal function, cardiac hypertrophy, glucose
      intolerance, hyperinsulinemia, anemia, and hypertension. Insulin sensitivity was
      significantly reduced in the uremic animals as determined by oral glucose
      tolerance tests. After six weeks of uremia, at a point when cardiac hypertrophy
      had been established, left ventricle tissue had a marked increase in the
      expression of GLUT4 (insulin-dependent glucose transporter 4), consistent with
      hypertrophic remodeling, but not GLUT1 (insulin-independent glucose transporter
      1). However, although uremic animals had systemic insulin resistance and glucose
      intolerance, there was no evidence of impaired GLUT4 translocation in the heart
      at 6 weeks of uremia, suggesting that other mechanisms may underpin insulin
      resistance in the uremic heart.

PMID- 19177157
TI  - Ischemic and non-ischemic acute kidney injury cause hepatic damage.
AB  - Recent studies have documented that remote organs are affected by ischemic injury
      to the kidney. Here we studied whether the liver also suffers damage during
      induction of renal ischemia-reperfusion in rats and compared this to bilateral
      nephrectomy. Hepatic levels of tumor necrosis factor-alpha increased
      significantly after 6 and 24 h of renal ischemia or nephrectomy. Malondialdehyde,
      an index of lipid peroxidation, increased while total glutathione was decreased
      in the liver in both the renal ischemia and nephrectomy groups, suggesting
      activation of oxidative stress. Expression of liver spermine-spermidine acetyl
      transferase, an enzyme upregulated in early phases of hepatic injury was
      significantly increased 6 h after either kidney ischemia or nephrectomy.
      Apoptosis was increased in hepatocytes 24 h after nephrectomy. We also found
      histological evidence of hepatocyte injury following both ischemia and bilateral
      nephrectomy. Infusion of reduced glutathione, before the induction of renal
      ischemia, significantly improved liver architecture and was associated with a
      reduction in hepatic malondialdehyde and serum alanine transaminase levels. Our
      study shows that acute kidney ischemia or renal failure activates oxidative
      stress and promotes inflammation, apoptosis, and tissue damage in hepatocytes.

PMID- 19177158
TI  - Glomeruli of Dense Deposit Disease contain components of the alternative and
      terminal complement pathway.
AB  - Dense Deposit Disease (DDD), or membranoproliferative glomerulonephritis type II,
      is a rare renal disease characterized by dense deposits in the mesangium and
      along the glomerular basement membranes that can be seen by electron microscopy.
      Although these deposits contain complement factor C3, as determined by
      immunofluorescence microscopy, their precise composition remains unknown. To
      address this question, we used mass spectrometry to identify the proteins in
      laser microdissected glomeruli isolated from paraffin-embedded tissue of eight
      confirmed cases of DDD. Compared to glomeruli from five control patients, we
      found that all of the glomeruli from patients with DDD contain components of the
      alternative pathway and terminal complement complex. Factor C9 was uniformly
      present as well as the two fluid-phase regulators of terminal complement complex
      clusterin and vitronectin. In contrast, in nine patients with immune complex
      mediated membranoproliferative glomerulonephritis, glomerular samples contained
      mainly immunoglobulins and complement factors C3 and C4. Our study shows that in
      addition to fluid-phase dysregulation of the alternative pathway, soluble
      components of the terminal complement complex contribute to glomerular lesions
      found in DDD.

PMID- 19177159
TI  - Oligosaccharide composition is similar in drusen and dense deposits in
      membranoproliferative glomerulonephritis type II.
AB  - Drusen are a feature of age-related macular degeneration (AMD). Lesions similar
      in appearance to drusen are also found in the fundi of patients with
      membranoproliferative glomerulonephritis type II (dense deposit disease, DDD).
      The lamina densa of the glomerular basement membrane, in DDD, is transformed into
      an electron-dense structure by deposition of microscopically homogeneous
      material. Our study sought to compare the saccharide composition of drusen and
      dense deposits in the formalin-fixed, paraffin-embedded tissue from the eye and
      kidney. Six eye specimens were obtained from patients diagnosed with AMD but
      another eye was obtained from a patient with partial lipodystrophy, who died
      after renal failure presumably because of DDD. The kidney specimens were from
      three biopsy-proven cases of DDD. Glycosylation patterns were measured by the
      binding of 19 biotinylated lectins before and after neuraminidase pre-treatment.
      High mannose, bi/tri-antennary non-bisected and bisected complex N-glycan, N
      acetyl glucosamine, galactose, and sialic acid residues were found in both drusen
      and dense deposits. Treatment with neuraminidase exposed subterminal galactose in
      both sites and sparse N-acetyl galactosamine residues in drusen alone. Our study
      found similar pathologic oligosaccharide structures in the eye and kidney,
      suggesting that drusen may be a common end result of retinal and glomerular
      disease.

PMID- 19177160
TI  - Mutations of NPHP2 and NPHP3 in infantile nephronophthisis.
AB  - Nephronophthisis is an autosomal recessive chronic tubulointerstitial disease
      that progresses to end-stage renal disease (ESRD) in about 10% of cases during
      infancy. Mutations in the INVS (NPHP2) gene were found in a few patients with
      infantile nephronophthisis. Mutations of NPHP3, known to be associated with
      adolescent nephronophthisis, were found in two patients with early-onset ESRD.
      Here we screened 43 families with infantile nephronophthisis (ESRD less than 5
      years of age) for NPHP2 and NPHP3 mutations and determined genotype-phenotype
      correlations. In this cohort there were 16 families with NPHP2 mutations and
      NPHP3 mutations in seven. Three patients carried only one heterozygous mutation
      in NPHP3. ESRD arose during the first 2 years of life in 16 of 18 patients with
      mutations in NPHP2, but in only two patients with mutations in NPHP3. Renal
      morphology, characterized by hyper-echogenic kidneys on ultrasound and tubular
      lesions with interstitial fibrosis on histology, was similar in the two patient
      groups. The kidney sizes were highly diverse and ultrasound-visualized cysts were
      present in a minority of cases. Extra-renal anomalies were found in 80% of the
      entire cohort including hepatic involvement (50%), cardiac valve or septal
      defects (20%) and recurrent bronchial infections (18%). We show that NPHP3
      mutations in both infantile and adolescent nephronophthisis point to a common
      pathophysiological mechanism despite their different clinical presentations.

PMID- 19177161
TI  - Canadian Ophthalmological Society evidence-based clinical practice guidelines for
      cataract surgery in the adult eye.

PMID- 19177162
TI  - Rhythmicity in mice selected for extremes in stress reactivity: behavioural,
      endocrine and sleep changes resembling endophenotypes of major depression.
AB  - BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis,
      including hyper- or hypo-activity of the stress hormone system, plays a critical
      role in the pathophysiology of mood disorders such as major depression (MD).
      Further biological hallmarks of MD are disturbances in circadian rhythms and
      sleep architecture. Applying a translational approach, an animal model has
      recently been developed, focusing on the deviation in sensitivity to stressful
      encounters. This so-called 'stress reactivity' (SR) mouse model consists of three
      separate breeding lines selected for either high (HR), intermediate (IR), or low
      (LR) corticosterone increase in response to stressors. METHODOLOGY/PRINCIPLE
      FINDINGS: In order to contribute to the validation of the SR mouse model, our
      study combined the analysis of behavioural and HPA axis rhythmicity with sleep
      EEG recordings in the HR/IR/LR mouse lines. We found that hyper-responsiveness to
      stressors was associated with psychomotor alterations (increased locomotor
      activity and exploration towards the end of the resting period), resembling
      symptoms like restlessness, sleep continuity disturbances and early awakenings
      that are commonly observed in melancholic depression. Additionally, HR mice also
      showed neuroendocrine abnormalities similar to symptoms of MD patients such as
      reduced amplitude of the circadian glucocorticoid rhythm and elevated trough
      levels. The sleep-EEG analyses, furthermore, revealed changes in rapid eye
      movement (REM) and non-REM sleep as well as slow wave activity, indicative of
      reduced sleep efficacy and REM sleep disinhibition in HR mice.
      CONCLUSION/SIGNIFICANCE: Thus, we could show that by selectively breeding mice
      for extremes in stress reactivity, clinically relevant endophenotypes of MD can
      be modelled. Given the importance of rhythmicity and sleep disturbances as
      biomarkers of MD, both animal and clinical studies on the interaction of
      behavioural, neuroendocrine and sleep parameters may reveal molecular pathways
      that ultimately lead to the discovery of new targets for antidepressant drugs
      tailored to match specific pathologies within MD.

PMID- 19177163
TI  - Novel biochemical markers of psychosocial stress in women.
AB  - BACKGROUND: Prolonged psychosocial stress is a condition assessed through self
      reports. Here we aimed to identify biochemical markers for screening and early
      intervention in women. METHODS: Plasma concentrations of interleukin (IL) 1
      alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma),
      tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1),
      epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), thyroid
      stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4),
      prolactin, and testosterone were measured in: 195 women on long-term sick-leave
      for a stress-related affective disorder, 45 women at risk for professional
      burnout, and 84 healthy women. RESULTS: We found significantly increased levels
      of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress.
      Statistical analysis indicates that they independently associate with a
      significant risk for being classified as ill. CONCLUSIONS: MCP-1, EGF, and VEGF
      are potential markers for screening and early intervention in women under
      prolonged psychosocial stress.

PMID- 19177164
TI  - Chronic mild stress (CMS) in mice: of anhedonia, 'anomalous anxiolysis' and
      activity.
AB  - BACKGROUND: In a substantial proportion of depressed patients, stressful life
      events play a role in triggering the evolution of the illness. Exposure to stress
      has effects on different levels in laboratory animals as well and for the rat it
      has been shown that chronic mild stress (CMS) can cause antidepressant-reversible
      depressive-like effects. The adoption of the model to the mouse seems to be
      problematic, depending on the strain used and behavioural endpoint defined. Our
      aim was to evaluate the applicability of CMS to mice in order to induce
      behavioural alterations suggested to reflect depression-like symptoms.
      METHODOLOGY/PRINCIPAL FINDINGS: A weekly CMS protocol was applied to male mice of
      different mouse strains (D2Ola, BL/6J and BL/6N) and its impact on stress
      sensitive behavioural measures (anhedonia-, anxiety- and depression-related
      parameters) and body weight was assessed. Overnight illumination as commonly used
      stressor in CMS protocols was particularly investigated in terms of its effect on
      general activity and subsequently derived saccharin intake. CMS application
      yielded strain-dependent behavioural and physiological responses including
      'paradox' anxiolytic-like effects. Overnight illumination was found to be
      sufficient to mimic anhedonic-like behaviour in BL/6J mice when being applied as
      sole stressor. CONCLUSIONS/SIGNIFICANCE: The CMS procedure induced some
      behavioural changes that are compatible with the common expectations, i.e.
      'anhedonic' behaviour, but in parallel behavioural alterations were observed
      which would be described as 'anomalous' (e.g. decreased anxiety). The results
      suggest that a shift in the pattern of circadian activity has a particular high
      impact on the anhedonic profile. Changes in activity in response to novelty seem
      to drive the 'anomalous' behavioural alterations as well.

PMID- 19177165
TI  - The methyl-CpG binding proteins Mecp2, Mbd2 and Kaiso are dispensable for mouse
      embryogenesis, but play a redundant function in neural differentiation.
AB  - BACKGROUND: The precise molecular changes that occur when a neural stem (NS) cell
      switches from a programme of self-renewal to commit towards a specific lineage
      are not currently well understood. However it is clear that control of gene
      expression plays an important role in this process. DNA methylation, a mark of
      transcriptionally silent chromatin, has similarly been shown to play important
      roles in neural cell fate commitment in vivo. While DNA methylation is known to
      play important roles in neural specification during embryonic development, no
      such role has been shown for any of the methyl-CpG binding proteins (Mecps) in
      mice. METHODOLOGY/PRINCIPAL FINDINGS: To explore the role of DNA methylation in
      neural cell fate decisions, we have investigated the function of Mecps in mouse
      development and in neural stem cell derivation, maintenance, and differentiation.
      In order to test whether the absence of phenotype in singly-mutant animals could
      be due to functional redundancy between Mecps, we created mice and neural stem
      cells simultaneously lacking Mecp2, Mbd2 and Zbtb33. No evidence for functional
      redundancy between these genes in embryonic development or in the derivation or
      maintenance of neural stem cells in culture was detectable. However evidence for
      a defect in neuronal commitment of triple knockout NS cells was found.
      CONCLUSIONS/SIGNIFICANCE: Although DNA methylation is indispensable for mammalian
      embryonic development, we show that simultaneous deficiency of three methyl-CpG
      binding proteins genes is compatible with apparently normal mouse embryogenesis.
      Nevertheless, we provide genetic evidence for redundancy of function between
      methyl-CpG binding proteins in postnatal mice.

PMID- 19177166
TI  - Retinal pathology of pediatric cerebral malaria in Malawi.
AB  - INTRODUCTION: The causes of coma and death in cerebral malaria remain unknown.
      Malarial retinopathy has been identified as an important clinical sign in the
      diagnosis and prognosis of cerebral malaria. As part of a larger autopsy study to
      determine causes of death in children with coma presenting to hospital in
      Blantyre, Malawi, who were fully evaluated clinically prior to death, we examined
      the histopathology of eyes of patients who died and underwent autopsy.
      METHODOLOGY/PRINCIPAL FINDINGS: Children with coma were admitted to the pediatric
      research ward, classified according to clinical definitions as having cerebral
      malaria or another cause of coma, evaluated and treated. The eyes were examined
      by direct and indirect ophthalmoscopy. If a child died and permission was given,
      a standardized autopsy was carried out. The patient was then assigned an actual
      cause of death according to the autopsy findings. The eyes were examined
      pathologically for hemorrhages, cystoid macular edema, parasite sequestration and
      thrombi. They were stained immunohistochemically for fibrin and CD61 to identify
      the components of thrombi, beta-amyloid precursor protein to detect axonal
      damage, for fibrinogen to identify vascular leakage and for glial fibrillary
      acidic protein to detect gliosis. Sixty-four eyes from 64 patients were examined:
      35 with cerebral malaria and 29 with comas of other causes. Cerebral malaria was
      distinguished by sequestration of parasitized erythrocytes, the presence and
      severity of retinal hemorrhages, the presence of cystoid macular edema, the
      occurrence and number of fibrin-platelet thrombi, the presence and amount of
      axonal damage and vascular leakage. CONCLUSIONS/SIGNIFICANCE: We found
      significant differences in retinal histopathology between patients who died of
      cerebral malaria and those with other diagnoses. These histopathological findings
      offer insights into the etiology of malarial retinopathy and provide a
      pathological basis for recently described retinal capillary non-perfusion in
      children with malarial retinopathy. Because of the similarities between the
      retina and the brain it also suggests mechanisms that may contribute to coma and
      death in cerebral malaria.

PMID- 19177167
TI  - Crohn's disease and early exposure to domestic refrigeration.
AB  - BACKGROUND: Environmental risk factors playing a causative role in Crohn's
      Disease (CD) remain largely unknown. Recently, it has been suggested that
      refrigerated food could be involved in disease development. We thus conducted a
      pilot case control study to explore the association of CD with the exposure to
      domestic refrigeration in childhood. METHODOLOGY/PRINCIPAL FINDINGS: Using a
      standard questionnaire we interviewed 199 CD cases and 207 age-matched patients
      with irritable bowel syndrome (IBS) as controls. Cases and controls were followed
      by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The
      questionnaire focused on the date of the first acquisition of home refrigerator
      and freezer. Data were analysed by a multivariate logistic model. The current age
      was in average 34 years in CD cases and the percentage of females in the case and
      control groups were respectively 48.3% and 63.7%. Patients were exposed earlier
      than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator
      exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01
      4.29), P = 0.05). Comparable results were obtained looking for the exposure to
      freezer at home. Finally, among the other recorded items reflecting the hygiene
      and comfort at home, we also found personal television, car and washing machine
      associated with CD. CONCLUSION: This study supports the opinion that CD is
      associated with exposure to domestic refrigeration, among other household
      factors, during childhood.

PMID- 19177169
TI  - Mortality risk among children admitted in a large-scale nutritional program in
      Niger, 2006.
AB  - BACKGROUND: In 2006, the Medecins sans Frontieres nutritional program in the
      region of Maradi (Niger) included 68,001 children 6-59 months of age with either
      moderate or severe malnutrition, according to the NCHS reference (weight-for
      height<80% of the NCHS median, and/or mid-upper arm circumference<110 mm for
      children taller than 65 cm and/or presence of bipedal edema). Our objective was
      to identify baseline risk factors for death among children diagnosed with severe
      malnutrition using the newly introduced WHO growth standards. As the release of
      WHO growth standards changed the definition of severe malnutrition, which now
      includes many children formerly identified as moderately malnourished with the
      NCHS reference, studying this new category of children is crucial. METHODOLOGY:
      Program monitoring data were collected from the medical records of all children
      admitted in the program. Data included age, sex, height, weight, MUAC, clinical
      signs on admission including edema, and type of discharge (recovery, death, and
      default/loss to follow up). Additional data included results of a malaria rapid
      diagnostic test due to Plasmodium falciparum (Paracheck) and whether the child
      was a resident of the region of Maradi or came from bordering Nigeria to seek
      treatment. Multivariate logistic regression was performed on a subset of 27,687
      children meeting the new WHO growth standards criteria for severe malnutrition
      (weight-for-height<-3 Z score, mid-upper arm circumference<110 mm for children
      taller than 65 cm or presence of bipedal edema). We explored two different
      models: one with only basic anthropometric data and a second model that included
      perfunctory clinical signs. PRINCIPAL FINDINGS: In the first model including only
      weight, height, sex and presence of edema, the risk factors retained were the
      weight/height(1.84) ratio (OR: 5,774; 95% CI: [2,284; 14,594]) and presence of
      edema (7.51 [5.12; 11.0]). A second model, taking into account supplementary data
      from perfunctory clinical examination, identified other risk factors for death:
      apathy (9.71 [6.92; 13.6]), pallor (2.25 [1.25; 4.05]), anorexia (1.89 [1.35;
      2.66]), fever>38.5 degrees C (1.83 [1.25; 2.69]), and age below 1 year (1.42
      [1.01; 1.99]). CONCLUSIONS: Although clinicians will continue to perform
      screening using clinical signs and anthropometry, these risk indicators may
      provide additional criteria for the assessment of absolute and relative risk of
      death. Better appraisal of the child's risk of death may help orientate the child
      towards either hospitalization or ambulatory care. As the transition from the
      NCHS growth reference to the WHO standards will increase the number of children
      classified as severely malnourished, further studies should explore means to
      identify children at highest risk of death within this group using simple and
      standardized indicators.

PMID- 19177168
TI  - The combined dexamethasone/CRH Test (DEX/CRH test) and prediction of acute
      treatment response in major depression.
AB  - BACKGROUND: In this study the predictive value of the combined dexamethasone/CRH
      test (DEX/CRH test) for acute antidepressant response was investigated.
      METHODOLOGY/PRINCIPAL FINDINGS: In 114 depressed inpatients suffering from
      unipolar or bipolar depression (sample 1) the DEX/CRH test was performed at
      admission and shortly before discharge. During their stay in the hospital
      patients received different antidepressant treatment regimens. At admission, the
      rate of nonsuppression (basal cortisol levels >75.3 nmol/l) was 24.6% and was not
      related to the later therapeutic response. Moreover, 45 out of 114 (39.5%)
      patients showed an enhancement of HPA axis function at discharge in spite of
      clinical improvement. In a second sample, 40 depressed patients were treated
      either with reboxetine or mirtazapine for 5 weeks. The DEX/CRH test was performed
      before, after 1 week, and after 5 weeks of pharmacotherapy. Attenuation of HPA
      axis activity after 1 week was associated with a more pronounced alleviation of
      depressive symptoms after 5-week mirtazapine treatment, whereas downregulation of
      HPA system activity after 5 weeks was related to clinical response to reboxetine.
      However, early improvement of HPA axis dysregulation was not necessarily followed
      by a beneficial treatment outcome. CONCLUSIONS/SIGNIFICANCE: Taken together,
      performance of a single DEX/CRH test does not predict the therapeutic response.
      The best predictor for response seems to be an early attenuation of HPA axis
      activity within 1 or 2 weeks. However, early improvement of HPA system
      dysfunction is not a sufficient condition for a favourable response. Since a
      substantial part of depressive patients display a persistence of HPA axis
      hyperactivity at discharge, downregulation of HPA system function is not a
      necessary condition for acute clinical improvement either. Our data underline the
      importance of HPA axis dysregulation for treatment outcome in major depression,
      although restoration of HPA system dysfunction seems to be neither a necessary
      nor a sufficient determinant for acute treatment response.

PMID- 19177170
TI  - Timing is critical for effective glucocorticoid receptor mediated repression of
      the cAMP-induced CRH gene.
AB  - Glucocorticoid negative feedback of the hypothalamus-pituitary-adrenal axis is
      mediated in part by direct repression of gene transcription in glucocorticoid
      receptor (GR) expressing cells. We have investigated the cross talk between the
      two main signaling pathways involved in activation and repression of
      corticotrophin releasing hormone (CRH) mRNA expression: cyclic AMP (cAMP) and GR.
      We report that in the At-T20 cell-line the glucocorticoid-mediated repression of
      the cAMP-induced human CRH proximal promoter activity depends on the relative
      timing of activation of both signaling pathways. Activation of the GR prior to or
      in conjunction with cAMP signaling results in an effective repression of the cAMP
      induced transcription of the CRH gene. In contrast, activation of the GR 10
      minutes after onset of cAMP treatment, results in a significant loss of GR
      mediated repression. In addition, translocation of ligand-activated GR to the
      nucleus was found as early as 10 minutes after glucocorticoid treatment.
      Interestingly, while both signaling cascades counteract each other on the CRH
      proximal promoter, they synergize on a synthetic promoter containing 'positive'
      response elements. Since the order of activation of both signaling pathways may
      vary considerably in vivo, we conclude that a critical time-window exists for
      effective repression of the CRH gene by glucocorticoids.

PMID- 19177172
TI  - Towards the total chemical synthesis of integral membrane proteins: a general
      method for the synthesis of hydrophobic peptide-thioester building blocks.
AB  - Modification of a peptide-(alpha)thioester with a sequence of six arginines on
      the thioester leaving group can render soluble all peptides derived from a
      polytopic integral membrane protein. This strategy greatly simplifies the
      synthesis of peptide-(alpha)thioester building blocks for the total chemical
      synthesis of integral membrane proteins by native chemical ligation.

PMID- 19177171
TI  - Identification of retinal ganglion cells and their projections involved in
      central transmission of information about upward and downward image motion.
AB  - The direction of image motion is coded by direction-selective (DS) ganglion cells
      in the retina. Particularly, the ON DS ganglion cells project their axons
      specifically to terminal nuclei of the accessory optic system (AOS) responsible
      for optokinetic reflex (OKR). We recently generated a knock-in mouse in which
      SPIG1 (SPARC-related protein containing immunoglobulin domains 1)-expressing
      cells are visualized with GFP, and found that retinal ganglion cells projecting
      to the medial terminal nucleus (MTN), the principal nucleus of the AOS, are
      comprised of SPIG1+ and SPIG1(-) ganglion cells distributed in distinct mosaic
      patterns in the retina. Here we examined light responses of these two subtypes of
      MTN-projecting cells by targeted electrophysiological recordings. SPIG1+ and
      SPIG1(-) ganglion cells respond preferentially to upward motion and downward
      motion, respectively, in the visual field. The direction selectivity of SPIG1+
      ganglion cells develops normally in dark-reared mice. The MTN neurons are
      activated by optokinetic stimuli only of the vertical motion as shown by Fos
      expression analysis. Combination of genetic labeling and conventional retrograde
      labeling revealed that axons of SPIG1+ and SPIG1(-) ganglion cells project to the
      MTN via different pathways. The axon terminals of the two subtypes are organized
      into discrete clusters in the MTN. These results suggest that information about
      upward and downward image motion transmitted by distinct ON DS cells is
      separately processed in the MTN, if not independently. Our findings provide
      insights into the neural mechanisms of OKR, how information about the direction
      of image motion is deciphered by the AOS.

PMID- 19177173
TI  - Clinical Research After Catastrophic Disasters: Lessons Learned From Hurricane
      Katrina.
AB  - When catastrophic disasters such as Hurricane Katrina strike, psychologists and
      other mental health professionals often wonder how to use resources and fill
      needed roles. We argue that conducting clinical research in response to disasters
      is 1 important way that these professionals can contribute. However, we recognize
      that designing and implementing a clinical research study can be a daunting task,
      particularly in the context of the personal and system-wide chaos that follows
      most disasters. Thus, we offer a detailed description of our own experiences with
      conducting clinical research as part of our response to Hurricane Katrina. We
      describe our study design, recruitment and data collection efforts, and summarize
      and synthesize the lessons we have learned from this endeavor. Our hope is that
      others who may wish to conduct disaster-related research will learn from our
      mistakes and successes.

PMID- 19177174
TI  - An unsteady microfluidic T-form mixer perturbed by hydrodynamic pressure.
AB  - An unsteady microfluidic T-form mixer driven by pressure disturbances was
      designed and investigated. The performance of the mixer was examined both through
      numerical simulation and experimentation. Linear Stokes equations were used for
      these low Reynolds number flows. Unsteady mixing in a micro-channel of two
      aqueous solutions differing in concentrations of chemical species was described
      using a convection-dominated diffusion equation. The task was greatly simplified
      by employing linear superimposition of a velocity field for solving a scalar
      species concentration equation. Low-order-based numerical codes were found not to
      be suitable for simulation of a convection-dominated mixing process due to
      erroneous computational dissipation. The convection-dominated diffusion problem
      was addressed by designing a numerical algorithm with high numerical accuracy and
      computational-cost effectiveness. This numerical scheme was validated by
      examining a test case prior to being applied to the mixing simulation. Parametric
      analysis was performed using this newly developed numerical algorithm to
      determine the best mixing conditions. Numerical simulation identified the best
      mixing condition to have a Strouhal number (St)of 0.42. For a T-junction mixer
      (with channel width = 196 MUm), about 75% mixing can be finished within a mixing
      distance of less than 3 mm (i.e. 15 channel width) at St = 0.42 for flow with a
      Reynolds number less than 0.24. Numerical results were validated experimentally
      by mixing two aqueous solutions containing yellow and blue dyes. Visualization of
      the flow field under the microscope revealed a high level of agreement between
      numerical simulation and experimental results.

PMID- 19177175
TI  - AUTOMATIC CLASSIFICATION OF QUESTION TURNS IN SPONTANEOUS SPEECH USING LEXICAL
      AND PROSODIC EVIDENCE.
AB  - The ability to identify speech acts reliably is desirable in any spoken language
      system that interacts with humans. Minimally, such a system should be capable of
      distinguishing between question-bearing turns and other types of utterances.
      However, this is a non-trivial task, since spontaneous speech tends to have
      incomplete syntactic, and even ungrammatical, structure and is characterized by
      disfluencies, repairs and other non-linguistic vocalizations that make simple
      rule based pattern learning difficult. In this paper, we present a system for
      identifying question-bearing turns in spontaneous multi-party speech (ICSI
      Meeting Corpus) using lexical and prosodic evidence. On a balanced test set, our
      system achieves an accuracy of 71.9% for the binary question vs. non-question
      classification task. Further, we investigate the robustness of our proposed
      technique to uncertainty in the lexical feature stream (e.g. caused by speech
      recognition errors). Our experiments indicate that classification accuracy of the
      proposed method is robust to errors in the text stream, dropping only about 0.8%
      for every 10% increase in word error rate (WER).

PMID- 19177176
TI  - Novel morphologies and non-linear scaling of laser damage in glass by tightly
      focused femtosecond pulses.
AB  - We examine the relationship between pulse energy and the morphology of damage in
      glass, produced by a tightly-focused femtosecond pulsed laser. For fluences up to
      three times that of threshold, an unexpected discontinuity in the scaling of
      damage size is caused by ejection of rings of material surrounding central damage
      that appear above a sharp threshold fluence. A mechanism for the production of
      these structures via thermal expansion and shockwave generation is proposed.

PMID- 19177177
TI  - Learning to Reach to Locations Encoded from Imaging Displays.
AB  - The present study investigated how people learn to correct errors in actions
      directed toward cognitively encoded spatial locations. Subjects inserted a stylus
      to reach a hidden target localized by means of ultrasound imaging and portrayed
      with a scaled graph. As was found previously (Wu et al., 2005), subjects
      initially underestimated the target location but corrected their responses when
      given training with feedback. Three experiments were conducted to examine whether
      the error correction occurred at (1) the mapping from the input to a mental
      representation of target location; (2) the mapping from the representation of
      target location to the intended insertion response, or (3) the mapping from
      intended response to action. Experiment 1 and Experiment 3 disconfirmed Mappings
      1 and 3, respectively, by showing that training did not alter independent
      measures of target localization or the action of aiming. Experiment 2 showed that
      the output of Mapping 2, the planned response -- measured as the initial
      insertion angle -was corrected over trials, and the correction magnitude
      predicted the response to a transfer stimulus with a new represented location.

PMID- 19177178
TI  - SEASONALITY, PARASITE DIVERSITY, AND LOCAL EXTINCTIONS IN PLASMODIUM FALCIPARUM
      MALARIA.
AB  - We incorporate stochastic, density-dependent seasonal recruitment in adult
      Anopheles mosquito populations in a discrete-event model of Plasmodium falciparum
      malaria transmission and find the probabilities of parasite extinction higher
      than with perennial transmission. Seasonal fluctuations in vector populations act
      to synchronize the dynamics of infection and immunity in host populations,
      leading to fluctuations in parasite prevalence greater than expected solely on
      the basis of high- and low-season vector densities. This synchronization also
      biases frequencies of infection with multiple parasite phenotypes or genotypes.

PMID- 19177179
TI  - The future of liquid chromatography-mass spectrometry (LC-MS) in metabolic
      profiling and metabolomic studies for biomarker discovery.
AB  - The future utility of liquid chromatography-mass spectrometry (LC-MS) in
      metabolic profiling and metabolomic studies for biomarker discover will be
      discussed, beginning with a brief description of the evolution of metabolomics
      and the utilization of the three most popular analytical platforms in such
      studies: NMR, GC-MS, and LC-MS. Emphasis is placed on recent developments in high
      efficiency LC separations, sensitive electrospray ionization approaches, and the
      benefits to incorporating both in LC-MS-based approaches. The advantages and
      disadvantages of various quantitative approaches are reviewed, followed by the
      current LC-MS-based tools available for candidate biomarker characterization and
      identification. Finally, a brief prediction on the future path of LC-MS-based
      methods in metabolic profiling and metabolomic studies is given.

PMID- 19177180
TI  - Inferences and Power Analysis Concerning Two Negative Binomial Distributions with
      An Application to MRI Lesion Counts Data.
AB  - In comparing the mean count of two independent samples, some practitioners would
      use the t-test or the Wilcoxon rank sum test while others may use methods based
      on a Poisson model. It is not uncommon to encounter count data that exhibit
      overdispersion where the Poisson model is no longer appropriate. This paper deals
      with methods for overdispersed data using the negative binomial distribution
      resulting from a Poisson-Gamma mixture. We investigate the small sample
      properties of the likelihood-based tests and compare their performances to those
      of the t-test and of the Wilcoxon test. We also illustrate how these procedures
      may be used to compute power and sample sizes to design studies with response
      variables that are overdispersed count data. Although methods are based on
      inferences about two independent samples, sample size calculations may also be
      applied to problems comparing more than two independent samples. It will be shown
      that there is gain in efficiency when using the likelihood-based methods compared
      to the t-test and the ilcoxon test. In studies where each observation is very
      costly, the ability to derive smaller sample size estimates with the appropriate
      tests is not only statistically, but also financially, appealing.

PMID- 19177181
TI  - Social Support for Divorced Fathers' Parenting: Testing a Stress-Buffering Model.
AB  - A stress-buffering hypothesis for parenting was tested in a county-representative
      sample of 218 divorced fathers. Social support for parenting (emergency and
      nonemergency child care, practical support, financial support) was hypothesized
      to moderate effects of stress (role overload, coparental conflict, and daily
      hassles) on fathers' quality parenting. No custody fathers relied more on
      relatives compared with custodial fathers, who relied more on new partners for
      parenting support. No differences by custody status were found on levels of
      support or parenting over time. Parenting support buffered effects of change in
      role overload and coparenting conflict on coercive parenting and buffered effects
      of change in daily hassles on prosocial parenting. Buffer effects were more
      predictive over time. Implications for practice and preventive intervention
      strategies are discussed.

PMID- 19177182
TI  - Enzymatic Processing of Amelogenin during Continuous Crystallization of Apatite.
AB  - Dental enamel forms through a protein-controlled mineralization and enzymatic
      degradation with a nanoscale precision that new engineering technologies may be
      able to mimic. Recombinant full-length human amelogenin (rH174) and a matrix
      metalloprotease (MMP-20) were employed in a pH-stat titration system that enabled
      a continuous supply of calcium and phosphate ions over several days, mimicking
      the initial stages of matrix processing and crystallization in enamel in-vitro.
      Effects on the self-assembly and crystal growth from a saturated aqueous solution
      containing 0.4 mg/ml rH174 and MMP-20 with the weight ratio of 1:1000 with
      respect to rH174 were investigated. A transition from nanospheres to fibrous
      amelogenin assemblies was facilitated under conditions that involved an
      interaction between rH174 and the proteolytic cleavage products. Despite
      continuous titration, the levels of calcium exhibited a consistent trend of
      decreasing, thereby indicating its possible role in the protein self-assembly.
      This study suggests that mimicking enamel formation in-vitro requires the synergy
      between the aspects of matrix self-assembly, proteolysis and crystallization.

PMID- 19177183
TI  - Therapeutic antioxidant medical gas.
AB  - Medical gases are pharmaceutical gaseous molecules which offer solutions to
      medical needs and include traditional gases, such as oxygen and nitrous oxide, as
      well as gases with recently discovered roles as biological messenger molecules,
      such as carbon monoxide, nitric oxide and hydrogen sulphide. Medical gas therapy
      is a relatively unexplored field of medicine; however, a recent increasing in the
      number of publications on medical gas therapies clearly indicate that there are
      significant opportunities for use of gases as therapeutic tools for a variety of
      disease conditions. In this article, we review the recent advances in research on
      medical gases with antioxidant properties and discuss their clinical applications
      and therapeutic properties.

PMID- 19177186
TI  - The Association between Concentrations of Green Tea and Blood Glucose Levels.
AB  - Our objective was to examine whether habitual green tea consumption is associated
      with blood glucose levels and other biomarkers of glucose metabolism. We
      conducted a cross-sectional study of 35 male volunteers, 23-63 years old and
      residing in Shizuoka Prefecture in Japan. Biochemical data were measured and we
      conducted a questionnaire survey on health, lifestyle, and nutrition, as well as
      frequency of consumption and concentrations (1%, 2%, and 3%) of green tea. Men
      who consumed a 3% concentration of green tea showed lower mean values of fasting
      blood glucose and fructosamine than those who consumed a 1% concentration.
      Fasting blood glucose levels were found to be significantly associated with green
      tea concentration (beta = -0.14, p = 0.03). However, green tea consumption
      frequency showed no significant differences in mean levels of blood glucose,
      fructosamine and hemoglobin A(1c.) In conclusion, our findings suggest that the
      consumption of green tea at a high concentration has the potential to reduce
      blood glucose levels.

PMID- 19177184
TI  - N(epsilon)-(Carboxymethyl)lysine and Coronary Atherosclerosis-Associated Low
      Density Lipoprotein Abnormalities in Type 2 Diabetes: Current Status.
AB  - In comparison to the general population, individuals with diabetes suffer a 3- to
      4-fold increased risk for developing complications of atherosclerosis and
      vascular insufficiency. This fact should be taken into account to develop a
      suitable determinant for the early detection of these complications and
      subsequently reduce the adverse effect of type 2 diabetes. In vitro experiments
      have shown that the products of glucose auto-oxidation and Amadori adducts are
      both potential sources of N(epsilon)-(carboxymethyl)lysine (CML). Excessive
      formation of CML on low density lipoprotein (LDL) has been proposed to be an
      important mechanism for the dyslipidemia and accelerated atherogenesis observed
      in patients with type 2 diabetes. It has been postulated that the uptake of CML
      LDL by LDL receptors is impaired, thereby decreasing its clearance from the blood
      circulation. Alternatively, the uptake of these modified LDL particles by
      scavenger receptors on macrophages and vascular smooth muscle cells (SMCs) and by
      AGE receptors on endothelial cells, SMCs, and monocytes is highly enhanced and
      this, in turn, is centrally positioned to contribute to the pathogenesis of
      diabetic vascular complications especially coronary artery disease. The present
      review summarizes the up-to-date information on effects and mechanism of type 2
      diabetes-associated coronary atherosclerosis induced by CML-LDL modification.

PMID- 19177187
TI  - Efficient assay for total antioxidant capacity in human plasma using a 96-well
      microplate.
AB  - In the present study, we tried to establish an efficient assay for total
      antioxidant capacity (TAC) in human plasma using a 96-well microplate. TAC was
      assessed using lag time by antioxidants against the myoglobin-induced oxidation
      of 2,2'-azino-di(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) with hydrogen
      peroxide, and expressed as Trolox equivalent. The linearity of the calibration
      curve with Trolox was maintained with the Trolox concentration range from 2.5
      microM to 25 microM (R(2) = 0.997). The assay was applied to the measurement of
      TAC in healthy human plasma. Coefficient of variation in intraday assay was 2.4%.
      Difference was not observed in interday assay. Plasma TAC of men ((569 +/- 41)
      microM Trolox equivalent; n = 6) was higher than that of women ((430 +/- 28)
      microM Trolox equivalent; n = 4). After the vegetable juice was drunk for 1 week,
      the increase in plasma TAC was observed in almost all the volunteers. In summary,
      we developed the efficient assay for plasma TAC using a 96-well microplate.

PMID- 19177185
TI  - Heme Oxygenase-1 is an Essential Cytoprotective Component in Oxidative Tissue
      Injury Induced by Hemorrhagic Shock.
AB  - Hemorrhagic shock causes oxidative stress that leads to tissue injuries in
      various organs including the lung, liver, kidney and intestine. Excess amounts of
      free heme released from destabilized hemoproteins under oxidative conditions
      might constitute a major threat because it can catalyze the formation of reactive
      oxygen species. Cells counteract this by rapidly inducing the rate-limiting
      enzyme in heme breakdown, heme oxygenase-1 (HO-1), which is a low-molecular
      weight stress protein. The enzymatic HO-1 reaction removes heme. As such,
      endogenous HO-1 induction by hemorrhagic shock protects tissues from further
      degeneration by oxidant stimuli. In addition, prior pharmacological induction of
      HO-1 ameliorates oxidative tissue injuries induced by hemorrhagic shock. In
      contrast, the deletion of HO-1 expression, or the chemical inhibition of
      increased HO activity ablated the beneficial effect of HO-1 induction, and
      exacerbates tissue damage. Thus, HO-1 constitutes an essential cytoprotective
      component in hemorrhagic shock-induced oxidative tissue injures. This article
      reviews recent advances in understanding of the essential role of HO-1 in
      experimental models of hemorrhagic shock-induced oxidative tissue injuries with
      emphasis on the role of its induction in tissue defense.

PMID- 19177188
TI  - Bay leaves improve glucose and lipid profile of people with type 2 diabetes.
AB  - Bay leaves (Laurus nobilis) have been shown to improve insulin function in vitro
      but the effects on people have not been determined. The objective of this study
      was to determine if bay leaves may be important in the prevention and/or
      alleviation of type 2 diabetes. Forty people with type 2 diabetes were divided
      into 4 groups and given capsules containing 1, 2 or 3 g of ground bay leaves per
      day for 30 days or a placebo followed by a 10 day washout period. All three
      levels of bay leaves reduced serum glucose with significant decreases ranging
      from 21 to 26% after 30 d. Total cholesterol decreased, 20 to 24%, after 30 days
      with larger decreases in low density lipoprotein (LDL) cholesterol of 32 to 40%.
      High density lipoprotein (HDL) cholesterol increased 29 and 20% in the groups
      receiving 1 and 2 g of bay leaves, respectively. Triglycerides also decreased 34
      and 25% in groups consuming 1 and 2 g of bay leaves, respectively, after 30 d.
      There were no significant changes in the placebo group. In summary, this study
      demonstrates that consumption of bay leaves, 1 to 3 g/d for 30 days, decreases
      risk factors for diabetes and cardiovascular diseases and suggests that bay
      leaves may be beneficial for people with type 2 diabetes.

PMID- 19177189
TI  - 8-Oxo-7,8-dihydro-2'-deoxyguanosine Forms a Relatively Unstable Tetrameric
      Structure Compared with 2'-Deoxyguanosine.
AB  - The hydrogen-bonded guanine tetrad, or G-quartet has been implicated in a variety
      of biological roles, including the function of chromosome telomeres. Here effect
      of the hydroxylation of guanosine at the 8 position on the G-quartet formation
      was examined. Electrospray inonization mass (ESI-MS) spectra of 8-oxo-7,8-dihydro
      2'-deoxyguanosine (8-oxodG) and 2'-deoxyguanosine (dG) were measured in order to
      know whether or not 8-oxodG forms a tetrameric structure as 2'-deoxyguanosine
      forms in teromeres. The ESI-MS spectra of dG shows prominent peaks at m/z 290,
      m/z 557, and m/z 1092, corresponding to [dG + Na](+), [dG2 + Na](+), and [dG(4) +
      Na](+) in the presence of 0.1 mM NaCl. On the other hand, the ESI-MS spectra of 8
      oxodG in the presence of 0.1 mM NaCl shows prominent peaks at m/z 306 and m/z
      589, corresponding to [8-oxodG + Na](+) and [8-oxodG(2) + Na](+). The results
      showed that 8-oxodG forms a relatively unstable tetrameric structure compared
      with dG.

PMID- 19177190
TI  - In Vitro Effects of the Reduced Form of Coenzyme Q(10) on Secretion Levels of TNF
      alpha and Chemokines in Response to LPS in the Human Monocytic Cell Line THP-1.
AB  - Ubiquinol-10 (QH(2)), the reduced form of Coenzyme Q(10) (CoQ(10)) serves as a
      potent antioxidant of lipid membranes. Because many antioxidants reveal potent
      anti-inflammatory effects, the influence of QH(2) on lipopolysaccharide (LPS)
      induced pro-inflammatory cytokines and chemokines were determined in the human
      monocytic cell line THP-1. Stimulation of cells with LPS resulted in a distinct
      release of Tumour necrosis factor-alpha (TNF-alpha), Macrophage inflammatory
      protein-1 alpha (MIP-1alpha), Regulated upon activation, normal T cell expressed
      and secreted (RANTES) and Monocyte chemotattractant protein-1 (MCP-1). The LPS
      induced responses were significantly decreased by pre-incubation of cells with
      QH(2) to 60.27 +/- 9.3% (p = 0.0009), 48.13 +/- 6.93% (p = 0.0007) and 74.36 +/-
      7.25% (p = 0.008) for TNF-alpha, MIP-1alpha and RANTES, respectively. In
      conclusion, our results indicate anti-inflammatory effects of the reduced form of
      CoQ(10) on various proinflammatory cytokines and chemokines in vitro.

PMID- 19177191
TI  - Quantification of Modified Tyrosines in Healthy and Diabetic Human Urine using
      Liquid Chromatography/Tandem Mass Spectrometry.
AB  - The quantification of urinary oxidized tyrosines, dityrosine (DiY), nitrotyrosine
      (NY), bromotyrosine (BrY), and dibromotyrosine (DiBrY), was accomplished by
      quadruple liquid chromatography-tandem mass spectrometry (LC/MS/MS). The sample
      was partially purified by solid phase extraction, and was then applied to the
      LC/MS/MS using multiple-reaction monitoring (MRM) methods. The analysis for the
      DiY quantification was done first. The residual samples were further butylated
      with n-butanol/HCl, and the other modified tyrosines were then quantified with
      isotopic dilution methods. MRM peaks of the modified tyrosines (DiY, NY, BrY, and
      DiBrY) from human urine were measured and the elution times coincided with the
      authentic and isotopic standards. The amounts of modified tyrosines in healthy
      human urine (n = 23) were 8.8 +/- 0.6 (DiY), 1.4 +/- 0.4 (NY), 3.8 +/- 0.3 (BrY),
      and 0.7 +/- 0.1 (DiBrY) micromol/mol of creatinine, respectively. A comparison of
      the modified tyrosines with urinary 8-oxo-deoxyguanosine, pentosidine, and
      N(epsilon)-(hexanoyl)lysine was also performed. Almost all products, except for
      NY, showed good correlations with each other. The amounts of the modified
      tyrosines (NY, BrY, and DiBrY) in the diabetic urine were higher than those in
      the urine from healthy people.

PMID- 19177192
TI  - Dimethoxycurcumin, a Synthetic Curcumin Analogue, Induces Heme Oxygenase-1
      Expression through Nrf2 Activation in RAW264.7 Macrophages.
AB  - Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] induces
      heme oxygenase-1 (HO-1) expression via activation of the nuclear factor-erythroid
      2-related factor 2 (Nrf2), whereas tetrahydrocurcumin [1,7-bis(4-hydroxy-3
      methoxyphenyl)-3,5-heptanedione], one of curcumin in vivo metabolites, has no
      effect on HO-1 expression and Nrf2 activation. The aim of this study was to
      investigate whether dimethoxycurcumin [1,7-bis(4,3-dimethoxyphenyl)-1,6
      heptadiene-3,5-dione], a synthetic curcumin analogue with higher metabolic
      stability over curcumin, could induce HO-1 expression to the same extent as
      curcumin in RAW264.7 macrophages. Dimethoxycurcumin and curcumin, but not
      tetrahydrocurcumin, induced HO-1 expression and Nrf2 nuclear translocation,
      suggesting that the unsaturated nature of the diarylheptanoid chain of the
      compounds are crucial for HO-1 expression and Nrf2 activation. Blockage of Nrf2
      synthesis by small interfering RNA abolished HO-1 expression by
      dimethoxycurcumin, indicating that dimethoxycurcumin may induce HO-1 expression
      via Nrf2 activation. In comparison, dimethoxycurcumin and curcumin had about the
      same effect on HO-1 expression, suggesting that dimethoxycurcumin retains the HO
      1-inducing activity of its parent compound curcumin in RAW264.7 macrophages.

PMID- 19177193
TI  - Effects of exogenous antioxidants on dietary iron overload.
AB  - In dietary iron overload, excess hepatic iron promotes liver damage. The aim was
      to attenuate free radical-induced liver damage using vitamins. Four groups of 60
      Wistar rats were studied: group 1 (control) was fed normal diet, group 2 (Fe)
      2.5% pentacarbonyl iron (CI) followed by 0.5% Ferrocene, group 3 (Fe + V gp) CI,
      Ferrocene, plus vitamins A and E (42x and 10x RDA, respectively), group 4 (Fe - V
      gp) CI, Ferrocene diet, minus vitamins A and E. At 20 months, glutathione
      peroxidase (GPx), superoxide dismutase (SOD), Oxygen Radical Absorbance Capacity
      (ORAC), Ames mutagenicity test, AST, ALT and 4-hydroxynonenal (4-HNE)
      immunohistochemistry were measured. 8OHdG levels of the Fe + V and Fe - V groups
      were 346 +/- 117 and 455 +/- 151, ng/g w.wt, respectively. Fe + V and Fe - V
      differences were significant (p<0.005). A positive correlation between DNA damage
      and mutagenesis existed (p<0.005) within the iron-fed gps. AST levels for Fe + V
      and Fe - V groups were 134.6 +/- 48.6 IU and 202.2 +/- 50.5 IU, respectively.
      Similarly, ALT levels were 234.6 +/- 48.3 IU and 329.0 +/- 48.6 IU, respectively.
      However, Fe - V and Fe + V groups transaminases were statistically insignificant.
      4-HNE was detected in Fe + V and Fe - V gp livers. Vitamins A and E could not
      prevent hepatic damage.

PMID- 19177194
TI  - Preparation and Characterization of a Polyclonal Antibody against Brominated
      Protein.
AB  - (Di)bromotyrosine is formed by the specific reaction of eosinophil peroxidase and
      can be used as an eosinophil activation marker. In the present study, an antibody
      for (di)bromotyrosine in proteins was prepared to investigate the pathogenesis of
      eosinophil-related diseases such as allergic responses. A rabbit polyclonal
      antibody was raised against brominated keyhole limpet hemocyanin. The specificity
      of the antiserum was investigated with an enzyme-linked immunosorbent assay
      (ELISA). The antiserum recognized brominated bovine serum albumin (BSA) and
      dibromotyrosine-conjugated BSA. The antiserum also reacted with chlorinated BSA
      and di-iodotyrosine-conjugated BSA. Moreover, the specificity of the antiserum
      was investigated using competitive ELISA. Dibromotyrosine and di-iodotyrosine
      inhibited the recognition of brominated BSA by the antiserum. However, the
      recognition of brominated BSA by the antiserum was not inhibited by
      bromotyrosine, chlorotyrosine, iodotyrosine, nitrotyrosine, aminotyrosine,
      phosphotyrosine, or tyrosine. These results suggested that the epitope of the
      antiserum is dihalogenated tyrosine. Immunohistochemically, the antiserum stained
      brominated rat eosinophils but not chlorinated or nitrated eosinophils. In
      conclusion, an antiserum for dihalogenated protein was prepared. It is expected
      that the antiserum will be useful for the analysis of the pathogenesis of
      allergic diseases such as asthma and atopic dermatitis.

PMID- 19177195
TI  - The +299(G>A) resistin gene polymorphism and susceptibility to type 2 diabetes in
      Thais.
AB  - The prevalence of type 2 diabetes has been increased in Thais. Resistin is an
      adipokine that involve in glucose homeostasis and is a candidate gene for type 2
      diabetes. We performed a case-control study in representative sample of 200 Thai
      volunteers, 105 controls and 95 type 2 diabetes subjects. The purposes of the
      present study were to investigate the association between two SNPs (single
      nucleotide polymorphisms) in the resistin gene, at positions +299(G>A) and 
      420(C>G), and biochemical parameters; to determine whether these polymorphisms
      are linked to increased risk of type 2 diabetes. At position +299(G>A) of the
      resistin gene, the resistin concentration among type 2 diabetes subjects was
      significantly higher in GA/AA genotypes (3.40 ng/ml) than the GG genotype (1.99
      ng/ml). Resistin gene polymorphism at position +299(G>A) in type 2 diabetes
      patients was significantly more frequent than in the control group (p = 0.004).
      Polymorphism at position -420(C>G) showed no significant relationship with type 2
      diabetes (p = 0.095). Logistic regression analysis was shown that +299(G>A) gene
      polymorphism was increased risk factors for type 2 diabetes (p = 0.013). In
      conclusion, these finding suggest that resistin gene polymorphism at position
      +299(G>A) has impact on the increased resistin concentrations and may influence
      susceptibility to type 2 diabetes in Thais.

PMID- 19177196
TI  - Resuscitation of preterm infants with reduced oxygen results in less oxidative
      stress than resuscitation with 100% oxygen.
AB  - The objective of this study was to determine the effects of the level of inhaled
      oxygen during resuscitation on the levels of free radicals and anti-oxidative
      capacity in the heparinized venous blood of preterm infants. Forty four preterm
      infants <35 weeks of gestation with mild to moderate neonatal asphyxia were
      randomized into two groups. The first group of infants were resuscitated with
      100% oxygen (100% O(2) group), while in the other group (reduced O(2) group), the
      oxygen concentration was titrated according to pulse oximeter readings. We
      measured total hydroperoxide (TH) and redox potential (RP) in the plasma within
      60 min of birth. The integrated excessive oxygen ( summation operator(FiO(2)
      0.21) x Time(min)) was higher in the 100% O(2) group than in the reduced O(2)
      group (p<0.0001). TH was higher in the 100% O(2) group than in the reduced O(2)
      group (p<0.0001). RP was not different between the 100% O(2) and reduced O(2)
      groups (p = 0.399). RP/TH ratio was lower in the 100% O(2) group than in the
      reduced O(2) group (p<0.01). We conclude that in the resuscitation of preterm
      infants with mild to moderate asphyxia, oxidative stress can be reduced by
      lowering the inspired oxygen concentration using a pulse oximeter.

PMID- 19177197
TI  - Aberrant promoter methylation of SPARC in ovarian cancer.
AB  - Epigenetic silencing of tumor suppressor genes is a new focus of investigation in
      the generation and proliferation of carcinomas. Secreted protein acidic and rich
      in cysteine (SPARC) is reportedly detrimental to the growth of ovarian cancer
      cells and has been shown to be epigenetically silenced in several cancers. We
      hypothesized that SPARC is downregulated in ovarian cancer through aberrant
      promoter hypermethylation. To that end, we analyzed SPARC expression in ovarian
      cancer cell lines and investigated the methylation status of the Sparc promoter
      using methylation-specific polymerase chain reaction. Our results show that SPARC
      mRNA expression is decreased in three (33%) and absent in four (44%) of the nine
      ovarian cancer cell lines studied, which correlated with hypermethylation of the
      Sparc promoter. Treatment with the demethylating agent 5-aza-2'-deoxycytidine
      rescued SPARC mRNA and protein expression. Addition of exogenous SPARC, as well
      as ectopic expression by an adenoviral vector, resulted in decreased
      proliferation of ovarian cancer cell lines. Investigation of primary tumors
      revealed that the Sparc promoter is methylated in 68% of primary ovarian tumors
      and that the levels of SPARC protein decrease as the disease progresses from low
      to high grade. Lastly, de novo methylation of Sparc promoter was shown to be
      mediated by DNA methyltransferase 3a. These results implicate Sparc promoter
      methylation as an important factor in the genesis and survival of ovarian
      carcinomas and provide new insights into the potential use of SPARC as a novel
      biomarker and/or treatment modality for this disease.

PMID- 19177198
TI  - Enhanced ovarian cancer tumorigenesis and metastasis by the macrophage colony
      stimulating factor.
AB  - Coexpression of the macrophage colony-stimulating factor (CSF-1) and its receptor
      (CSF-1R) in metastatic ovarian cancer specimens is a predictor of poor outcome in
      epithelial ovarian cancer. This suggests that an autocrine loop is produced by
      which ovarian tumors can secrete CSF-1 stimulating the CSF-1R resulting in a more
      aggressive phenotype. Our current work sought to validate this autocrine
      stimulation model using stable transfection of a 4-kb CSF-1 construct into
      otherwise nonvirulent Bix3 ovarian cancer cells. A representative clone,
      Bix3T8.2, produced a 72-fold increase in CSF-1 gene transcription rate (by
      nuclear run-off assays) and a 57-fold increase in secreted CSF-1 protein (by
      sandwich ELISA), compared to parent cells. Comparison of Bix3T8.2 invasion,
      adhesion, and motility in vitro and metastasis in vivo were made to parental and
      transfectant controls. Up to 12-fold higher invasiveness was seen with Bix3T8.2
      and 2- and 6-fold higher adhesion and motility, respectively, over controls in
      vitro. In nude mice, i.p. injection of Bix3T8.2 produced a wide array of
      visceral, nodal, and distant metastasis with a degree of enhanced tumor burden
      not seen in any of the 10 mice inoculated with transfectant control cells.
      Complete absence of tumor take distinguished 40% of mice implanted with
      transfectant control cells. Disruption of this autocrine loop using antisense
      oligomer therapy against CSF-1R and 3' untranslated region knockdown of CSF-1
      protein resulted in reversal of in vitro and in vivo tumor phenotypes. This CSF-1
      feedback loop offers a model by which novel biologic therapies can potentially
      target multiple levels of this pathway.

PMID- 19177199
TI  - Enhanced antitumorigenic effects in glioblastoma on double targeting of
      pleiotrophin and its receptor ALK.
AB  - In adults, glioblastomas are the most lethal and most frequent malignant brain
      tumors, and the poor prognosis despite aggressive treatment indicates the need to
      establish novel targets for molecular intervention. The secreted growth factor
      pleiotrophin (PTN, HB-GAM, HBNF, OSF-1) shows mitogenic, chemotactic, and
      transforming activity. Whereas PTN expression is tightly regulated during
      embryogenesis and is very limited in normal adult tissues, a marked PTN up
      regulation is seen in tumors including glioblastomas. Likewise, the PTN receptor
      anaplastic lymphoma kinase (ALK) has been shown previously to be upregulated and
      functionally relevant in glioblastoma. In this study, we explore the
      antitumorigenic effects of the simultaneous ribozyme-mediated knockdown of both
      receptor and ligand. Various glioblastoma cell lines are analyzed for PTN and ALK
      expression. Beyond the individual efficacies of several specific ribozymes
      against PTN or ALK, respectively, antiproliferative and proapoptotic effects of a
      single gene targeting approach are strongly enhanced on double knockdown of both
      genes in vitro. More importantly, this results in the abolishment of tumor growth
      in an in vivo subcutaneous tumor xenograft model. Finally, the analysis of
      various downstream signaling pathways by antibody arrays reveals a distinct
      pattern of changes in the activation of signal transduction molecules on PTN/ALK
      double knockdown. Beyond the already known ones, it identifies additional
      pathways relevant for PTN/ALK signaling. We conclude that double targeting of PTN
      and ALK leads to enhanced antitumorigenic effects over single knockdown
      approaches, which offers novel therapeutic options owing to increased efficacy
      also after prolonged knockdown.

PMID- 19177200
TI  - ZEB-1, a repressor of the semaphorin 3F tumor suppressor gene in lung cancer
      cells.
AB  - SEMA3F is a secreted semaphorin with potent antitumor activity, which is
      frequently downregulated in lung cancer. In cancer cell lines, SEMA3F
      overexpression decreases hypoxia-induced factor 1alpha protein and vascular
      endothelial growth factor mRNA, and inhibits multiple signaling components.
      Therefore, understanding how SEMA3F expression is inhibited in cancer cells is
      important. We previously defined the promoter organization of SEMA3F and found
      that chromatin remodeling by a histone deacetylase inhibitor was sufficient to
      activate SEMA3F expression. In lung cancer, we have also shown that ZEB-1, an E
      box transcription repressor, is predominantly responsible for loss of E-Cadherin
      associated with a poor prognosis and resistance to epidermal growth factor
      receptor inhibitors. In the present study, we demonstrated that ZEB-1 also
      inhibits SEMA3F in lung cancer cells. Levels of ZEB-1, but not ZEB-2, Snail or
      Slug, significantly correlate with SEMA3F inhibition, and overexpression or
      inhibition of ZEB-1 correspondingly affected SEMA3F expression. Four conserved E
      box sites were identified in the SEMA3F gene. Direct ZEB-1 binding was confirmed
      by chromatin immunoprecipitation assays for two of these, and ZEB-1 binding was
      reduced when cells were treated with a histone deacetylase inhibitor. These
      results demonstrate that ZEB-1 directly inhibits SEMA3F expression in lung cancer
      cells. SEMA3F loss was associated with changes in cell signaling: increased
      phospho-AKT in normoxia and increase of hypoxia-induced factor 1alpha protein in
      hypoxia. Moreover, exogenous addition of SEMA3F could modulate ZEB-1-induced
      angiogenesis in a chorioallantoic membrane assay. Together, these data provide
      further support for the importance of SEMA3F and ZEB-1 in lung cancer
      progression.

PMID- 19177202
TI  - Extratumoral macrophages promote tumor and vascular growth in an orthotopic rat
      prostate tumor model.
AB  - Tumor-associated macrophages are involved in angiogenesis and tumor progression,
      but their role and specific site of action in prostate cancer remain unknown. To
      explore this, Dunning R-3327 AT-1 rat prostate tumor cells were injected into the
      prostate of syngenic and immunocompetent Copenhagen rats and analyzed at
      different time points for vascular proliferation and macrophage density.
      Endothelial proliferation increased with tumor size both in the tumor and
      importantly also in the extratumoral normal prostate tissue. Macrophages
      accumulated in the tumor and in the extratumoral normal prostate tissue and were
      most abundant in the invasive zone. Moreover, only extratumoral macrophages
      showed strong positive associations with tumor size and extratumoral vascular
      proliferation. Treatment with clodronate-encapsulated liposomes reduced the
      monocyte/macrophage infiltration and resulted in a significant inhibition of
      tumor growth. This was accompanied by a suppressed proliferation in microvessels
      and in the extratumoral prostate tissue also in arterioles and venules. The AT-1
      tumors produced, as examined by RT(2) Profiler PCR arrays, numerous factors
      promoting monocyte recruitment, angiogenesis, and tissue remodeling. Several,
      namely, chemokine (C-C) ligand 2, fibroblast growth factor 2, matrix
      metalloproteinase 9, interleukin 1beta, interferon gamma, and transforming growth
      factor beta, were highly upregulated by the tumor in vivo compared with tumor
      cells in vitro, suggesting macrophages as a plausible source. In conclusion, we
      here show the importance of extratumoral monocytes/macrophages for prostate tumor
      growth, angiogenesis, and extratumoral arteriogenesis. Our findings identify
      tumor-associated macrophages and several chemotactic and angiogenic factors as
      potential targets for prostate cancer therapy.

PMID- 19177201
TI  - Hodgkin lymphoma cell lines are characterized by a specific miRNA expression
      profile.
AB  - Hodgkin lymphoma (HL) is derived from preapoptotic germinal center B cells,
      although a general loss of B cell phenotype is noted. Using quantitative reverse
      transcription-polymerase chain reaction and miRNA microarray, we determined the
      microRNA (miRNA) profile of HL and compared this with the profile of a panel of B
      cell non-Hodgkin lymphomas. The two methods showed a strong correlation for the
      detection of miRNA expression levels. The HL-specific miRNA included miR-17-92
      cluster members, miR-16, miR-21, miR-24, and miR-155. Using a large panel of cell
      lines, we found differential expression between HL and other B-cell lymphoma
      derived cell lines for 27 miRNA. A significant down-regulation in HL compared to
      non-Hodgkin lymphoma was observed only for miR-150. Next, we performed target
      gene validation of predicted target genes for miR-155, which is highly expressed
      in HL and is differentially expressed between HL and Burkitt lymphoma. Using
      luciferase reporter assays, we validated 11 predicted miR-155 target genes in
      three different HL cell lines. We demonstrated that AGTR1, FGF7, ZNF537, ZIC3,
      and IKBKE are true miR-155 target genes in HL.

PMID- 19177203
TI  - Cyclophosphamide enhances human tumor growth in nude rat xenografted tumor
      models.
AB  - The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX)
      on tumor growth was investigated in primary and metastatic intracerebral and
      subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg,
      intraperitoneally) 24 hours before human ovarian carcinoma (SKOV3), small cell
      lung carcinoma (LX-1 SCLC), and glioma (UW28, U87MG, and U251) tumor cells were
      inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere
      or were infused into the right internal carotid artery. Tumor development was
      monitored and recorded. Potential mechanisms were further investigated. Only
      animals that received both CTX and Matrigel showed consistent growth of
      subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage
      (83.3% vs 0%) of animals showing intraperitoneal tumors. In intracerebral
      implantation tumor models, CTX pretreatment increased the tumor volume and the
      percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma
      bone and facial metastases after intra-arterial injection, and 20% of animals
      showed brain metastases. Cyclophosphamide transiently decreased nude rat white
      blood cell counts and glutathione concentration, whereas serum vascular
      endothelial growth factor was significantly elevated. Cyclophosphamide also
      increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68
      positive) infiltration into glioma cell-inoculated rat brains. Cyclophosphamide
      may enhance primary and metastatic tumor growth through multiple mechanisms,
      including immune modulation, decreased response to oxidative stress, increased
      tumor vascularization, and increased macrophage infiltration. These findings may
      be clinically relevant because chemotherapy may predispose human cancer subjects
      to tumor growth in the brain or other tissues.

PMID- 19177204
TI  - Transcriptional regulation of urokinase-type plasminogen activator receptor by
      hypoxia-inducible factor 1 is crucial for invasion of pancreatic and liver
      cancer.
AB  - Angioinvasion is critical for metastasis with urokinase-type plasminogen
      activator receptor (uPAR) and tumor hypoxia-activated hypoxia-inducible factor 1
      (HIF-1) as key players. Transcriptional control of uPAR expression by HIF has
      never been reported. The aim of the present study, therefore, was to test whether
      tumor hypoxia-induced HIF expression may be linked to transcriptional activation
      of uPAR and dependent angioinvasion. We used human pancreatic cancer cells and a
      model of parental and derived HIF-1beta-deficient mouse liver cancer cell lines
      and performed Northern blot analysis, nuclear runoff assays, electrophoretic
      mobility shift assay, polymerase chain reaction-generated deletion mutants,
      luciferase assays, Matrigel invasion assays, and in vivo angioinvasion assays in
      the chorioallantoic membrane of fertilized chicken eggs. Urokinase-type
      plasminogen activator receptor promoter analysis resulted in four putative HIF
      binding sites. Hypoxia strongly induced de novo transcription of uPAR mRNA. With
      sequential deletion mutants of the uPAR promoter, it was possible to identify one
      HIF binding site causing a nearly 200-fold increase in luciferase activity.
      Hypoxia enhanced the number of invading tumor cells in vitro and in vivo. In
      contrast, HIF-1beta-deficient cells failed to upregulate uPAR expression, to
      activate luciferase activity, and to invade on hypoxia. Taken together, we show
      for the first time that uPAR is under transcriptional control of HIF and that
      this is important for hypoxia-induced metastasis.

PMID- 19177206
TI  - Cross-diffusion and pattern formation in reaction-diffusion systems.
AB  - Cross-diffusion, the phenomenon in which a gradient in the concentration of one
      species induces a flux of another chemical species, has generally been neglected
      in the study of reaction-diffusion systems. We summarize experiments that
      demonstrate that cross-diffusion coefficients can be quite significant, even
      exceeding "normal," diagonal diffusion coefficients in magnitude in systems that
      involve ions, micelles, complex formation, excluded volume effects (e.g., surface
      or polymer reactions) and other phenomena commonly encountered in situations of
      interest to chemists. We then demonstrate with a series of model calculations
      that cross-diffusion can lead to spatial and spatiotemporal pattern formation,
      even in relatively simple systems. We also show that, in the absence of cross
      diffusion among the reacting species, introduction of a nonreactive species that
      induces appropriate cross-diffusive fluxes with reactive species can lead to
      pattern formation.

PMID- 19177205
TI  - Proteomic identification of LASP-1 down-regulation after RNAi urokinase silencing
      in human hepatocellular carcinoma cells.
AB  - In human hepatocellular carcinoma (HCC), the high expression of urokinase-type
      plasminogen activator (uPA) is an unfavorable prognostic factor and a therapeutic
      target. To identify the downstream effects of uPA silencing by RNA interference,
      we studied proteome modifications of uPA-inhibited SKHep1C3 cells, an HCC-derived
      cell line. The study with two-dimensional difference gel electrophoresis and
      matrix-assisted laser desorption/ionization-time of flight-mass spectrometry
      showed Lim and SH3 protein 1 (LASP-1), cytokeratin 1 (CK-1), cytokeratin 10 (CK
      10), and heterogeneous nuclear ribonucleoprotein H1 down-modulation after uPA
      inhibition. LASP-1, CK-1, and CK-10 are involved in cytoskeleton dynamics as
      heterogeneous nuclear ribonucleoprotein H1 takes part in the mRNA processing and
      stability. We first confirmed the proteomic data by Western blot and
      immunoflorescence and then explored the link between uPA and LASP-1. The ectopic
      expression of uPA and LASP-1 supported the proteomic results and showed that uPA
      up-regulation increased LASP-1 expression and that both were implicated in
      SKHep1C3 motility. siRNA LASP-1 inhibition showed that LASP-1 was involved in
      actin microfilaments organization of SKHep1C3 cells. The disruption of the actin
      microfilaments after LASP-1 depletion increased uPA secretion and SKHep1C3
      motility. Our results would suggest the hypothesis that uPA and LASP-1 expression
      may be coordinated in HCC-derived cells. In summary, the proteomic identification
      of a set of uPA downstream proteins provides new insight into the function of uPA
      in HCC cells.

PMID- 19177207
TI  - Universal scaling of charge transport in glass-forming ionic liquids.
AB  - Charge transport and glassy dynamics of a variety of glass-forming ionic liquids
      (ILs) are investigated in a wide frequency and temperature range by means of
      broadband dielectric spectroscopy, differential scanning calorimetry and
      rheology. While the absolute values of dc conductivity and viscosity vary over
      more than 11 decades with temperature and upon systematic structural variation of
      the ILs, quantitative agreement is found between the characteristic frequency of
      charge transport and the structural alpha-relaxation. This is traced back to
      dynamic glass transition assisted hopping as the underlying mechanism of charge
      transport.

PMID- 19177208
TI  - Spectroscopic and microcalorimetric study of a TiO(2)-supported platinum
      catalyst.
AB  - This paper reports a CO adsorption study on a Pt/TiO(2) catalyst reduced at two
      different temperatures, 473 and 773 K, followed by in situ infrared spectroscopy
      and adsorption microcalorimetry. The study is complemented with XPS
      characterization of the reduced catalysts.

PMID- 19177209
TI  - Does spin-orbit coupling effect favor planar structures for small platinum
      clusters?
AB  - We have performed relativistic effective core potential calculations with and
      without spin-orbit coupling term in the framework of the density functional
      theory and investigated the geometry and binding energy of different isomers of
      free platinum clusters Pt(n) (n = 4-6) for the spin multiplicities from singlet
      to nonet. The spin-orbit coupling effect has been discussed for the minimum
      energy structures, relative stabilities, vibrational frequencies, magnetic
      moments, and the highest occupied and lowest unoccupied molecular-orbital gaps.
      It is found in contrast to some of the previous calculations that 3-D
      configurations are still lowest energy structures of these clusters, although
      spin-orbit effect makes some planar or quasi-planar geometries more stable than
      some other 3-D isomers. Spin-orbit coupling effects change the relative stability
      of various isomers.

PMID- 19177210
TI  - Interaction of CHX(3) (X = F, Cl, Br) with HNO induces remarkable blue shifts of
      both C-H and N-H bonds.
AB  - The hydrogen-bonded complexes formed from interaction of trihalomethanes CHX(3)
      (X = F, Cl, Br) with nitrosyl hydride HNO were studied using ab initio MO
      calculations at the second-order perturbation theory (MP2/6-311++G(d,p)). Each
      interaction contains at least five separate equilibrium structures. Calculated
      binding energies range from 4 to 8 kJ mol(-1) with both ZPE and BSSE corrections.
      While CHBr(3) leads to the most stable complexes with HNO, CHF(3) forms the least
      stable counterparts. The strength of complexes thus tends to increase from F to
      Cl to Br, which is consistent with a decrease of deprotonation enthalpy of the
      corresponding C-H bonds. It is remarkable that all the C-H and N-H bonds are
      shortened upon complexation, giving rise to an increase of their stretching
      frequencies. A blue shift is thus observed for the N-H bonds of the type N-HX (X
      = F, Cl, Br); such a contraction of the covalent N-H bond is extremely rare.

PMID- 19177211
TI  - Mass spectrometric investigation and formation mechanisms of high-mass species in
      the downstream region of Ar/CF(4)/O(2) plasmas.
AB  - Mass analysis has been conducted on the positive ions and neutral species in the
      downstream region of Ar/CF(4)/O(2) plasmas. The neutral species have been ionized
      by Li(+) attachment before mass analysis. The CF(2)O(+), C(2)F(5)O(+) and
      C(n)F(2n-1)O(+) (1 <or=n<or= 6) positive ions and the C(n)F(2n)O (1 <or=n<or= 7)
      neutral species have been found as the species composed of C, F and O. The
      intensity of C(2)F(4)O observed via the Li(+)-attachment mass spectra has been
      exceptionally weak in comparison to the intensities of CF(2)O and C(3)F(6)O. In
      addition, neither C(2)F(4) nor C(3)F(6) have been observed, although C(n)F(2n)
      (n>or= 4) have been observed as the species composed only of C and F. These
      findings suggest that C(n)F(2n)O (n>or= 3) are produced mainly through the
      following reactions: CF(3)(CF(2))(m)CF = CF(2) + O((3)P) --> CF(2)((3)B(1)) +
      CF(3)(CF(2))(m)CFO (m>or= 1) and CF(3)(CF(2))(m)CF = CF(CF(2))(n)CF(3) + O((3)P) 
      -> CF(3)(CF(2))(m)CF + CF(3)(CF(2))(n)CFO (m, n>or= 1), where the CF(3)(CF(2))(n)
      group might have side chains, as in (CF(3))(2)CF(CF(2))(n-2)-. With the help of
      quantum chemistry calculations of reaction enthalpies and transition states, the
      formation mechanisms of the observed species have been discussed in detail.

PMID- 19177212
TI  - A computational study on molecular adsorption states of nitrogen on a tungsten
      tetramer.
AB  - Molecular adsorption states of a dinitrogen (N(2)) on a free tungsten tetramer
      (W(4)) were investigated in detail by using a density functional theory method.
      It was found that adsorption states with end-on type geometries are the most
      energetically favorable for molecular adsorption. In the states, interaction
      between N(2) and W(4) is weak, and therefore the electronic structure of N(2) is
      not largely modified from that of a free N(2). There exist, however, another type
      of adsorption state with a W-N-N-W bridge-type binding configuration. In the
      adsorption state of this type, local N (s, p)-W (d) interactions are fairly
      stronger than in the end-on-type state, and, as a result of this, the adsorbed
      N(2) is significantly activated. The electronic structure of the bridge-type
      state explains a single-peaked X-ray photoelectron spectrum, previously observed
      experimentally for N(2) adsorbed on supported tungsten nanoclusters. The N 1s
      spectrum was found in our previous study of low-temperature N(2)O formation, and
      therefore, the bridge-type state is a possible candidate for a reaction precursor
      to the N(2)O formation under a mild condition.

PMID- 19177213
TI  - On the assignment of (19)F MAS NMR spectra of fluoroaluminates using through
      space spectral edition of (19)F-(27)Al and (19)F-(19)F connectivities.
AB  - Advantages and limitations of (19)F-(27)Al and (19)F-(19)F dipolar-based 2D NMR
      experiments for (19)F MAS spectra assignments of fluoroaluminates are presented.
      In beta-BaAlF(5), combination of 2D MAS (19)F-(27)Al CP-HETCOR and (19)F-(19)F DQ
      SQ NMR correlation experiments allows complete unambiguous assignment of the ten
      poorly resolved resonances of same relative intensities of the (19)F MAS NMR
      spectrum. The gain in resolution of the (19)F MAS 2D spectrum compared to a 1D
      spectrum is evidenced, allowing distinction of the two shared-fluorine resonances
      of Ba(3)Al(2)F(12). Limitations of the (19)F MAS DQ-SQ NMR experiment are shown
      for Ba(3)Al(2)F(12) and for alpha-CaAlF(5). For beta-BaAlF(5) and
      Ba(3)Al(2)F(12), final line assignments question those previously established
      from (19)F isotropic chemical shift calculations, which demonstrate that such
      experiments are essential for correct line assignments and assessment of
      calculation results.

PMID- 19177214
TI  - Microwave spectra of mixtures of non-absorbing solid particles and absorbing
      liquids.
AB  - Microwave spectroscopy of condensed phases is sensitive to sample compositional
      factors such as water or fat content, solids content and salt concentration which
      leads to applications for in-line process monitoring. In this paper we show that
      microwave spectra can also be sensitive to sample structure at fixed composition
      which has implications for analytical applications involving samples which are
      multi-phase mixtures. We have measured microwave spectra for samples containing a
      constant volume fraction of non-absorbing glass spheres immersed within an
      absorbing liquid phase; the only difference between samples is the mean diameter
      of the glass spheres. The large differences in the spectra for different
      diameters is successfully modelled in terms of the relative volume fractions of
      glass and absorbing liquid within a measurement penetration depth adjacent to the
      microwave measuring probe.

PMID- 19177215
TI  - Classical, quantum and statistical simulations of vibrationally excited HOSO(2):
      IVR, dissociation, and implications for OH + SO(2) kinetics at high pressures.
AB  - In this paper, we present classical and coupled coherent states quantum dynamics
      simulations to investigate intramolecular vibrational energy redistribution (IVR)
      from an excited (v = 1-10) OH stretch within the HOSO(2) complex to the other
      molecular bath modes. Using an analytical PES derived from electronic structure
      theory calculations, the results obtained from both the classical and quantum
      simulations are in reasonable agreement. The dynamics results suggest that
      statistical models overpredict HOSO(2) dissociation k(E)s, and underpredict the
      amount of vibrational excitation in the nascent OH formed following complex
      dissociation. In order to understand the dynamics results, we utilize a simple
      analytical model for describing energy flow from excited modes to bath modes, and
      show that IVR limits complex dissociation at short times. We also consider
      qualitative mass affects on IVR, and consider the implications of this work on
      previous measurements of the OH + SO(2) association k(infinity) using the proxy
      method.

PMID- 19177216
TI  - Molecular dynamics study of zinc binding to cysteines in a peptide mimic of the
      alcohol dehydrogenase structural zinc site.
AB  - The binding of zinc (Zn) ions to proteins is important for many cellular events.
      The theoretical and computational description of this binding (as well as that of
      other transition metals) is a challenging task. In this paper the binding of the
      Zn ion to four cysteine residues in the structural site of horse liver alcohol
      dehydrogenase (HLADH) is studied using a synthetic peptide mimic of this site.
      The study includes experimental measurements of binding constants, classical free
      energy calculations from molecular dynamics (MD) simulations and quantum
      mechanical (QM) electron structure calculations. The classical MD results account
      for interactions at the molecular level and reproduce the absolute binding energy
      and the hydration free energy of the Zn ion with an accuracy of about 10%. This
      is insufficient to obtain correct free energy differences. QM correction terms
      were calculated from density functional theory (DFT) on small clusters of atoms
      to include electronic polarisation of the closest waters and covalent
      contributions to the Zn-S coordination bond. This results in reasonably good
      agreement with the experimentally measured binding constants and Zn ion hydration
      free energies in agreement with published experimental values. The study also
      includes the replacement of one cysteine residue to an alanine. Simulations as
      well as experiments showed only a small effect of this upon the binding free
      energy. A detailed analysis indicate that the sulfur is replaced by three water
      molecules, thereby changing the coordination number of Zn from four (as in the
      original peptide) to six (as in water).

PMID- 19177217
TI  - Spectroscopic signatures for planar equilibrium geometries in methyl-substituted
      oligothiophenes.
AB  - In recent studies it was demonstrated that temperature-dependent optical
      spectroscopy is a valuable tool for revealing the differences in the geometries
      of flexible molecules like oligothiophenes (OTs) in the ground (S(0)) and first
      excited (S(1)) electronic states, by examining the symmetry relations between the
      absorption and emission spectra: while at low temperature the spectra show mirror
      symmetry, pointing to planar geometries in S(0) and S(1), the symmetry relation
      breaks down at ambient temperature due to thermal population of torsional modes.
      In the present joint spectroscopic and theoretical study, we demonstrate that
      this behavior is also observed for di- and tetramethyl-substituted OTs,
      suggesting an essentially planar equilibrium geometry not only in S(1) but also
      in S(0), despite the increasing sterical hindrance which is imposed by the
      substituents. This rather surprising result is rationalized by the softness of
      the carbon-sulfur bond, which is able to adapt to the geometrical constraints.

PMID- 19177219
TI  - Spectroscopy and dynamics of Mn(2+) in ZnS nanoparticles.
AB  - Both spectra of transient absorption (lambda(max) = 390 nm) and luminescence
      (lambda(max) = 590 nm) for the (4)T(1) state of Mn(2+) in ZnS nanoparticles shift
      to long wavelengths by 40 nm and broaden by 1.7 times as the state becomes
      banded. The (4)T(1) band of capping Mn(2+) in ZnS nanoparticles decays on the
      time scale of 0.35 mus, which is much shorter than either the decay time of the
      (4)T(1) state (2000 micros) for lattice-bound isolated Mn(2+) or that (180
      micros) for surface-bound isolated Mn(2+) in ZnS nanoparticles.

PMID- 19177218
TI  - Water penetration/accommodation and phase behaviour of the neutral Langmuir
      monolayer at the air/water interface probed with sum frequency generation
      vibrational spectroscopy (SFG-VS).
AB  - A strong and broad hydrogen bonded O-H band around 3520 cm(-1) is observed in the
      insoluble monolayer of the neutral liquid crystal molecules of 4''-n-pentyl-4-p
      cyanobiphenyl (5CB) and 4''-n-octyl-4-p-cyanobiphenyl (8CB) throughout the whole
      surface density range, but not in the 4-pentyl-4'-cyanoterphenyl (5CT) monolayer,
      at the air/water interface. This novel spectral feature suggests the existence of
      an oriented water cluster species which has penetrated or accommodated into the
      Langmuir monolayer of the 8CB and 5CB molecules. This finding provided a
      molecular level mechanism for the stark difference in the phase behaviour between
      the CB and CT insoluble Langmuir monolayers at the air/water interface. It also
      calls for attention to the details of the specific water-surface interaction in
      mediating the structure and the phase behaviour of the molecular assemblies at
      the heterogeneous aqueous interfaces.

PMID- 19177221
TI  - Heterologous expression systems for polyketide synthases.
AB  - Polyketide synthases are the main biochemical machinery for the production of a
      structurally diverse group of natural products, polyketides. Their heterologous
      expression enables overproduction of target compounds, generation of novel
      analogs, and provides a basic understanding of their reaction programs. This
      Highlight outlines the current state of heterologous expression of type I, type
      II, and type III polyketide synthases of microbial and plant origins.

PMID- 19177222
TI  - Marine natural products.
AB  - This review covers the literature published in 2007 for marine natural products,
      with 948 citations(627 for the period January to December 2007) referring to
      compounds isolated from marine microorganisms and phytoplankton, green algae,
      brown algae, red algae, sponges, cnidarians,bryozoans, molluscs, tunicates,
      echinoderms and true mangrove plants. The emphasis is on new compounds (961 for
      2007), together with the relevant biological activities, source organisms and
      country of origin. Biosynthetic studies, first syntheses, and syntheses that lead
      to the revision of structures or stereochemistries, have been included.1
      Introduction, 2 Reviews, 3 Marine microorganisms and phytoplankton, 4 Green
      algae, 5 Brown algae, 6 Red algae, 7 Sponges, 8 Cnidarians, 9 Bryozoans, 10
      Molluscs, 11 Tunicates (ascidians),12 Echinoderms, 13 Miscellaneous, 14
      Conclusion, 15 References.

PMID- 19177223
TI  - Marine natural products: synthetic aspects.
AB  - An overview of marine natural products synthesis during 2007 is provided. As with
      earlier installments in this series, the emphasis is on total syntheses of
      molecules of contemporary interest, new total syntheses, and syntheses that have
      resulted in structure confirmation or stereochemical assignments.1 Introduction,
      2 Review articles, 3 Azaspiracid, 4 Polyethers, 5 Guanidinium alkaloids, 6
      Amphidinolides, 7 Total syntheses of other compounds, 8 Acknowledgements, 9
      References.

PMID- 19177224
TI  - The biosynthesis of polyketide-derived polycyclic ethers.
AB  - The biosynthetic pathways to polyketide-derived polycyclic ethers, in bacteria,
      plants and marine organisms, have, until now, tended to be considered separately.
      The purpose of this article is to provide an integrated review of the common
      mechanistic aspects of polyether biosynthesis from these diverse sources. In
      particular, the focus will be on the proposed mechanisms of oxidative
      cyclisation, as well as on the known differences in polyketide chain construction
      between the terrestrial and marine polyethers.1 Introduction, 2 Fatty acid and
      polyketide biosynthesis, 3 Polyether ionophores, 4 The annonaceous acetogenins, 5
      Marine polyethers, 6 Chain construction in polyether biosynthesis, 7
      Acknowledgements, 8 References.

PMID- 19177225
TI  - Natural products from semi-mangrove flora: source, chemistry and bioactivities.
AB  - This review covers the source, chemistry and bioactivities of natural products
      from semi-mangrove species worldwide. The chemotaxonomy of semi-mangrove plants
      and total synthesis of heritol analogues, which are potential biocompatible
      pesticides, are discussed.1 Introduction, 2 Acanthaceae, 2.1 Acanthus, 2.1.1
      Aliphatic glycosides, 2.1.2 Alkaloids, 2.1.3 Flavonoids, 2.1.4 Lignan glycosides,
      2.1.5 Megastigmane and phenolic glycosides, 2.1.6 Phenylethanol glycosides, 2.1.7
      Triterpenoids, 2.1.8 Miscellaneous, 2.1.9 Bioactivities, 3 Euphorbiaceae, 3.1
      Excoecaria, 3.1.1 Diterpenoids, 3.1.2 Miscellaneous, 3.1.3 Bioactivities, 4
      Lythraceae, 4.1 Pemphis acidula, 5 Sterculiaceae, 5.1 Heritiera littoralis, 5.1.1
      Flavones, 5.1.2 Triterpenoids, 5.1.3 Benzene derivatives, 5.1.4 Sesquiterpenes,
      5.1.5 Steroids, 6 Total syntheses of heritol and its analogues, 7 Chemotaxonomy
      and concluding remarks, 8 Acknowledgements 9 References.

PMID- 19177226
TI  - Role of bacterial adhesion in the microbial ecology of biofilms in cooling tower
      systems.
AB  - The fate of the three heterotrophic biofilm forming bacteria, Pseudomonas
      aeruginosa, Klebsiella pneumoniae and Flavobacterium sp. in pilot scale cooling
      towers was evaluated both by observing the persistence of each species in the
      recirculating water and the formation of biofilms on steel coupons placed in each
      cooling tower water reservoir. Two different cooling tower experiments were
      performed: a short-term study (6 days) to observe the initial bacterial
      colonization of the cooling tower, and a long-term study (3 months) to observe
      the ecological dynamics with repeated introduction of the test strains. An
      additional set of batch experiments (6 days) was carried out to evaluate the
      adhesion of each strain to steel surfaces under similar conditions to those found
      in the cooling tower experiments. Substantial differences were observed in the
      microbial communities that developed in the batch systems and cooling towers. P.
      aeruginosa showed a low degree of adherence to steel surfaces both in batch and
      in the cooling towers, but grew much faster than K. pneumoniae and Flavobacterium
      in mixed-species biofilms and ultimately became the dominant organism in the
      closed batch systems. However, the low degree of adherence caused P. aeruginosa
      to be rapidly washed out of the open cooling tower systems, and Flavobacterium
      became the dominant microorganism in the cooling towers in both the short-term
      and long-term experiments. These results indicate that adhesion, retention and
      growth on solid surfaces play important roles in the bacterial community that
      develops in cooling tower systems.

PMID- 19177227
TI  - The composition of enamel salivary films is different from the ones formed on
      dental materials.
AB  - This study utilized two-dimensional gel electrophoresis (2DE) to illustrate the
      compositional differences between in vitro salivary conditioning films (denoted
      pellicles) formed on human enamel as well as on the dental materials titanium and
      poly(methyl methacrylate). The salivary pellicles were formed by immersing each
      surface in individual tubes containing small volumes of freshly collected whole
      saliva. Saliva remaining in the tubes after the pellicle formation for 2 h was
      visualized by means of 2DE and silver staining. The results showed that the
      protein patterns in 2DE of the liquid phase of saliva left after the exposure to
      the respective surfaces, regarding proteins <100 kDa in size, were different
      depending on the surface used. Several protein groups and/or individual proteins
      were shown to be distinct for each surface used.

PMID- 19177228
TI  - Neuroprotective role of heme-oxygenase 1 against iodoacetate-induced toxicity in
      rat cerebellar granule neurons: Role of bilirubin.
AB  - Heme oxygenase (HO) catalyses the breakdown of heme to iron, carbon monoxide and
      biliverdin, the latter being further reduced to bilirubin. A protective role of
      the inducible isoform, HO-1, has been described in pathological conditions
      associated with the production of reactive oxygen species (ROS). The aim of this
      study was to investigate the role of HO-1 in the neurotoxicity induced by
      iodoacetate (IAA) in primary cultures of cerebellar granule neurons (CGNs). IAA,
      an inhibitor of the glycolysis pathway, reduces cell survival, increases ROS
      production and enhances HO-1 expression in CGNs. Furthermore, the induction of HO
      1 expression by cobalt protoporphyrin (CoPP) prevented cell death and ROS
      production induced by IAA, whereas the inhibition of HO activity with tin
      mesoporphyrin exacerbated the IAA-induced neurotoxicity. The protective effect
      elicited by CoPP was reproduced by bilirubin addition, suggesting that this
      molecule may be involved in the protective effect of HO-1 induction in this
      experimental model.

PMID- 19177229
TI  - Two new steroidal saponins from the rhizome of Polygonatum sibiricum.
AB  - Two new furostanol saponins, polygonoides A (1) and B (2), along with three known
      compounds, were obtained from the ethanolic extract of the rhizome of Polygonatum
      sibiricum Redoute. On the basis of acid hydrolysis and comprehensive
      spectroscopic analyses, the structures of polygonoides A and B were elucidated as
      (25R)-26-O-beta-D-glucopyranosyl-furost-5,22(23)-dien-3beta,26-diol-3-O-alpha-L
      rhamnopyranosyl-(1 --> 3)-beta-D-glucopyranosyl-(1 --> 4)-[alpha-L
      rhamnopyranosyl-(1 --> 2)]-beta-D-glucopyranoside (1) and 22 alpha-(propionyloxy)
      furost-5-en-3beta,20 alpha-diol-3-O-beta-D-glucopyranosyl-(1 --> 4)-[alpha-L
      rhamnopyranosyl-(1 --> 2)]-beta-D-glucopyranoside (2).

PMID- 19177230
TI  - A new sesquiterpenoid metabolite from Psilocybe samuiensis.
AB  - A novel 2,3-secoaromadendrane-type sesquiterpenoid metabolite, psilosamuiensin A
      (1), was isolated from the broth of Psilocybe samuiensis. The structure of
      psilosamuiensin A was established by spectroscopic data and its configurations
      were confirmed by single crystal X-ray crystallographic analysis. This is the
      first report of psilosamuiensin A found in the genus Psilocybes.

PMID- 19177231
TI  - Syntheses of R-beta-rutinosides by rutin-degrading reaction.
AB  - Rutinose and five R-beta-rutinosides were obtained by means of rutin-degrading
      reaction in water or aqueous alcohol (ROH, R = methyl, ethyl, propyl, isopropyl,
      and benzyl) with rutin-degrading enzyme as catalyst and rutin as starting
      material in 84-94% yields, of which methyl-beta-rutinoside, propyl-beta
      rutinoside, isopropyl-beta-rutinoside, and benzyl-beta-rutinoside are firstly
      reported in this paper. Based on spectral analysis, the structures of all
      products were elucidated.

PMID- 19177232
TI  - Two new polyoxygenated cyclohexenes from Uvaria kweichowensis.
AB  - Two new polyoxygenated cyclohexenes, kweichowenols C and D, were isolated from
      the leaves of Uvaria kweichowensis, and their structures were established on the
      basis of their spectral data. The two new compounds showed some antitumor
      activity by the MTT assay.

PMID- 19177233
TI  - A new phenylpropanoid glycoside from Leucas indica Linn.
AB  - A new phenylpropanoid glycoside, alpha-L-rhamnopyranosyl-(1 --> 3)-O-alpha-L
      rhamnopyranosyl-(1 --> 6)-1-O-caffeoyl-beta-D-glucopyranoside (1) along with two
      known phenylethanoid glycosides (2-3) has been isolated from the aerial parts of
      Leucas indica Linn. Their structures were deduced from the spectroscopic studies
      and compared with the literature values.

PMID- 19177234
TI  - Sesquiterpenoids from Valeriana tangutica.
AB  - A new guaiane-type sesquiterpenoid ethoxyvalerianol (1) and one known
      sesquiterpenoid valeranone (2) together with selina-4,7(11)-diene (3) and
      selinene (4), which were obtained from (+)-maaliol (5) by decyclization and
      dehydration, were isolated from Valeriana tangutica. Their structures were
      elucidated by 1D- and 2D-NMR spectroscopic data and HR-ESI-MS analysis.

PMID- 19177235
TI  - Two new steroidal saponins from Tribulus terrestris.
AB  - Two new steroidal saponins and two known flavonoid glycosides were isolated from
      the fruits of Tribulus terrestris. Their structures were assigned by
      spectroscopic analysis and chemical reaction as 26-O-beta-D-glucopyranosyl-(25R)
      5 alpha-furostan-12-one-3beta,22 alpha,26-triol-3-O-beta-D-glucopyranosyl (1 -->
      2)-beta-D-glucopyranosyl(1 --> 4)-beta-D-galactopyranoside (1), 26-O-beta-D
      glucopyranosyl-(25S)-5 alpha-furostan-22-methoxy-2 alpha,3beta,26-triol-3-O-beta
      D-glucopyranosyl(1 --> 2)-beta-D-glucopyranosyl(1 --> 4)-beta-D-galactopyranoside
      (2), kaempferol-3-gentiobioside (3), and isorhamnetin-3-gentiobioside (4).

PMID- 19177236
TI  - Antioxidant constituents from Cotoneaster racemiflora.
AB  - A new lignan rhamnoside, racemiside (1), has been isolated from the ethyl acetate
      soluble fraction of Cotoneaster racemiflora, along with scopoletin (2), 7,8
      dimethoxy-6-hydroxycoumarin (3), 3,3',4'-tri-O-methylellagic acid (4), and
      cereotagloperoxide (5), reported for the first time from this species. All of
      them showed profound antioxidative activities in the DPPH assay.

PMID- 19177237
TI  - Coumarin glycosides from Euphorbia soongarica (Boiss).
AB  - Two new coumarin glycosides (1 and 2), along with six known compounds (3-8), were
      isolated from the roots of Euphorbia soongarica. The structures of two new
      compounds were elucidated as aesculetin-6-O-(6'-O-galloyl)-beta-D
      galactopyranoside (1) and fraxetin-8-O-(6'-O-galloyl)-beta-D-galactopyranoside
      (2) by spectral methods and chemical evidences.

PMID- 19177238
TI  - A new compound, brefeldin A formylate, from Penicillium sp. strain HLKG-44.
AB  - A novel compound named as brefeldin A formylate (1), together with two known
      compounds, brefeldin A (2) and ergosterol (3), was isolated from the Penicillium
      sp. strain HLKG-44, which was isolated from polluted environment in Fujian
      Province. Their structures were identified based on the spectral and X-ray
      crystallographic analyses. The compound 1, brefeldin A formylate, exhibited
      moderate cytotoxic activity against the human lung cancer cell line A549 with
      IC(50) value of 18.9 microg/ml by the MTT assay protocol.

PMID- 19177239
TI  - Novel N-containing rotenoid and seco-rotenoid from the root of Derris elliptica.
AB  - Two new rotenoids, 2-hydroxy-5-aminorotenonone (1) and elliptoic acid (2), were
      isolated from the roots of Derris elliptica collected in Guangdong Province,
      China. Their structures were established by extensive spectral analysis. Compound
      1 is the first N-containing rotenoid and compound 2 is the third rotenoid with
      the cleavage of C(12)-C(12a).

PMID- 19177240
TI  - Jacaranone analogs from Senecio scandens.
AB  - Bioassay-guided fractionation of the ethanolic extract of Senecio scandens led to
      the isolation of four new compounds 4, 5, 7, and 8, along with four known
      jacaranone analogs (1, 2, 3, 6). Their structures were elucidated on the basis of
      spectral and chemical evidence. Compound 7 was obtained as a tautomeric mixture
      of alpha/beta-epimer. The cytotoxic activities of these compounds were evaluated.
      Among these, compounds 5 and 8 showed potent cytotoxicities. The benzoquinone
      derivative, jacaranone ethyl ester (1), was the major cytotoxic constituent in
      this plant with IC(50)s at a range of 0.5-1.0 microg/ml against various tumor
      cell lines. The SAR of these jacaranone analogs (1-8), isolated from S. scandens,
      was also discussed.

PMID- 19177241
TI  - Phenylethanoid glycosides from the roots of Phlomis umbrosa.
AB  - The phytochemical study of the roots of Phlomis umbrosa Turcz. afforded three new
      phenylethanoid glycosides, 3'''-acetyl-O-betonyoside D (1), 2''', 3'''-di-acetyl
      O- betonyoside D (2), and 3''', 4'''-di-acetyl-O-betonyoside D (3), along with
      five known phenylethanoid glycosides. Their structures were elucidated on the
      basis of spectroscopic data. The antitumor activity of the isolated compounds was
      investigated.

PMID- 19177242
TI  - Chemical constituents from the bark of Cerbera manghas.
AB  - Two new compounds, 1,3-bis(m-carboxylphenyl)-propan-2-one (1) and 2-(m
      carboxylphenyl)-3-(m-carboxylbenzyl) succinic acid (2), were isolated from the
      barks of Cerbera manghas, and their structures were established on the basis of
      spectroscopic methods.

PMID- 19177243
TI  - Three new flavonol triglycosides from Derris trifoliata.
AB  - Three new flavonol triglycosides, kaempferol-3-O-alpha-L-rhamnopyranosyl-(1 -->
      6)-beta-D-glucopyranosyl-(1 --> 3)-beta-D-glucopyranoside (1), quercetin-3-O
      alpha-L-rhamnopyranosyl-(1 --> 6)-beta-D-glucopyranosyl-(1 --> 3)-beta-D
      glucopyranoside (2), quercetin-3-O-alpha-L-rhamnopyranosyl-(1 --> 6)-beta-D
      glucopyranosyl-(1 --> 2)-beta-D-glucopyranoside (3), together with the two known
      flavonol glycosides, kaempferol-3-O-alpha-L-rhamnopyranosyl-(1 --> 6)-beta-D
      glucopyranoside and kaempferol-3-O-alpha-L-rhamnopyranosyl-(1 --> 6)-beta-D
      glucopyranosyl-(1 --> 2)-beta-D-glucopyranoside, were isolated from the aerial
      parts of Derris trifoliata. Their structures were determined on the basis of
      chemical and spectroscopic analyses.

PMID- 19177244
TI  - Novel sesquiterpene and coumarin constituents from the whole herbs of
      Crossostephium chinense.
AB  - Novel sesquiterpene, named crossostephin (1), and coumarin, named biscopoletin
      (2), together with four known compounds, artesin, tanacetin, scopoletin, and
      scopolin, were isolated from the 70% ethanolic extract of the whole herbs of
      Crossostephium chinense (L.) Makino. Their structures were determined by
      spectroscopic methods, including IR, UV, EIMS, HRFTICRMS, 1D and 2D NMR spectral
      analyses. Both scopoletin and scopolin were isolated from the title plant for the
      first time.

PMID- 19177245
TI  - Chemical constituents from the seeds of Zanthoxylum alatum.
AB  - Chemical studies on the seeds of Zanthoxylum alatum Roxb. (Rutaceae) led to the
      isolation of two new phenolic constituents characterized as 3-methoxy-11-hydroxy
      6,8-dimethylcarboxylate biphenyl (3) and 3,5,6,7-tetrahydroxy-3',4'
      dimethoxyflavone-5-beta-D-xylopyranoside (6), along with the five known
      compounds, 1-methoxy-1,6,3-anthraquinone, 1-hydroxy-6,13-anthraquinone, 2
      hydroxybenzoic acid, 2-hydroxy-4-methoxy benzoic acid, and stigmasta-5-en-3beta-D
      glucopyranoside, on the basis of spectral data and chemical analyses.

PMID- 19177251
TI  - Gadolinium enhancement of the lumbar roots in a case of ALS.
AB  - We present a single case of clinically definite amyotrophic lateral sclerosis
      (ALS) associated with modest gadolinium enhancement of the lumbar nerve roots
      without thickening or nodularity and with CSF protein elevation (80 mg/dl). These
      findings should not exclude a clinical diagnosis of ALS and suggest that the
      enhancement of nerve roots and protein elevation were related to rapid neuronal
      degeneration, not inflammation.

PMID- 19177252
TI  - CSF profiles of angiogenic and inflammatory factors depend on the respiratory
      status of ALS patients.
AB  - Our objective was to assess the regulation of the hypoxia response of angiogenic
      and inflammatory factors from 76 cerebrospinal fluids (CSF) of sporadic
      amyotrophic lateral sclerosis (ALS) patients with different respiratory status.
      We first analysed the hypoxia response capacity by measuring CSF levels of
      angiogenin (ANG), VEGF, angiopoietin-2 (ANG-2) and PGE-2 in 40 ALS patients
      according to their hypoxaemia level and compared it with 40 neurological
      controls. We then compared the ANG, VEGF, EPO and ANG-2 CSF levels of 36 other
      ALS patients, divided into three groups with either 1) normoxaemia, 2)
      intermittent desaturation in the absence of hypoxaemia, or 3) chronic hypoxaemia
      with or without desaturation. We demonstrated a lack of up-regulation of both ANG
      and VEGF during hypoxaemia in ALS, compared with hypoxaemic controls. In
      contrast, PGE-2 and ANG-2 levels were increased in both hypoxaemic ALS patients
      and controls. ANG and VEGF levels did not increase in patients with long disease
      durations and with intermittent or chronic hypoxaemia. ANG-2 and EPO levels were
      up-regulated early in intermittent hypoxaemia and late in chronic hypoxaemia,
      respectively. Our results suggest alteration of the HIF-1alpha-mediated response
      to hypoxia during sporadic ALS, whereas the NFK-B pathway seems early activated.

PMID- 19177253
TI  - Life events, gender and suicidal behaviours in the acute community setting.
AB  - OBJECTIVE: The aim of this paper is to examine gender differences in relation to
      negative life events and suicidal behaviours in patients presenting to an acute
      community mental health team in Auckland, New Zealand. METHOD: Clinical files of
      all patients referred to one of the Auckland community crisis teams in 2007 were
      surveyed (n = 442). Those presenting with suicidal behaviours were included in
      the study ('suicidal behaviours' refers to the presence of suicidal ideas or
      suicide attempts). Demographic information and reasons for presentation were
      collected from the file. RESULTS: Seventy patients aged 18-65 years met the
      inclusion criteria. For 86% of women and 85% of men separation from their
      partners and relationship conflicts were the main stressors precipitating
      suicidal behaviours and referral to the local community crisis team. Suicidal
      behaviours did not differ between males and females. CONCLUSION: Irrespective of
      gender, relationship loss and conflicts were the most commonly identified
      negative life events precipitating suicidal behaviours in the acute community
      setting. These findings can have important implications in risk assessment,
      suicide prevention and provision of acute community services.

PMID- 19177254
TI  - Tumor locus moderates anxiety symptoms in a pediatric neuro-oncologic sample.
AB  - Despite the prevalence of pediatric Central Nervous System (CNS) solid tumors,
      little is understood about patients' disease-related anxiety experience. Data
      from 25 remitted pediatric CNS tumor patients posttreatment were collected.
      Significant symptoms of anxiety were reported by 32% of patients. MRI studies
      showed all anxious patients had right cortical tumors or left cerebellar tumors.
      Confound analyses suggest these results are not better accounted for by
      demographic, disease, or treatment variables. These results evidence the risk
      some pediatric neuro-oncologic patients face for developing significant anxiety
      symptoms.

PMID- 19177256
TI  - The degradation of (all-E)-beta-carotene by cigarette smoke.
AB  - The effects of cigarette smoke in promoting the degradation of (all-E)-beta
      carotene have been studied, but some conflicting results promoted a further
      study. beta-Carotene was solubilized in hexane and challenged with filtered
      cigarette smoke both at room temperature and at -20 degrees C. The products
      arising from smoke-induced oxidation were assessed using a combination of HLPC
      DAD, LC-MS and GC-MS. At room temperature the degradation of beta-carotene was
      very rapid, with only a few products being detected using HPLC-DAD. A range of
      volatile products including beta-ionone, beta-cyclocitral and 5,6-epoxy-beta
      ionone were detected using GC-MS. In contrast, when the reaction was slowed (by
      reducing the reaction temperature), a much wider range of products could be
      detected by HPLC-DAD, including 4-nitro-beta-carotene and several of its
      geometric isomers. These degradation products suggest that the C4 position on the
      beta-carotene end-group plays a key role in initiating free radical attack.

PMID- 19177255
TI  - Improved bleeding profile and tolerability of tibolone versus transdermal E2/NETA
      treatment in postmenopausal women with female sexual dysfunction.
AB  - OBJECTIVES: To compare the incidence of vaginal spotting/bleeding events and
      breast pain between therapy with tibolone 2.5 mg and continuous combined
      transdermal estradiol (E(2))/norethisterone acetate (NETA) 50 microg/140 microg
      after 24 weeks of treatment. METHODS: A double-blind, double-dummy, randomized,
      controlled trial was performed and assessments were performed at baseline, week
      12 and week 24. Bleeding/spotting events were recorded in a daily diary. Breast
      signs and symptoms were collected as adverse events. RESULTS: A total of 403
      women (mean age 56 years) were randomized. Bleeding/spotting events during weeks
      1-12 with tibolone and E(2)/NETA were experienced by 16% and 56% of women,
      respectively (p < 0.001). The corresponding percentages during weeks 13-24 were
      12% and 51%, respectively (p < 0.001). E(2)/NETA was significantly more likely
      than tibolone to be associated with vaginal hemorrhage (11% vs. 0%; p < 0.001)
      and breast signs and symptoms (11% vs. 4%; p = 0.015). Early discontinuations
      resulting from adverse events were significantly more common in the E(2)/NETA
      group than in the tibolone group (20% vs. 12%), primarily related to withdrawal
      due to vaginal hemorrhage (8% vs. 0%). CONCLUSIONS: Tibolone has a significantly
      better tolerability profile than transdermal E(2)/NETA as measured by vaginal
      bleeding, breast pain and treatment continuation.

PMID- 19177257
TI  - A study examining the safety and efficacy of a fractional laser in the treatment
      of photodamage on the hands.
AB  - BACKGROUND: Few clinical studies have been reported in the literature documenting
      the efficacy of non-ablative modalities in the treatment of non-facial areas such
      as the hand. OBJECTIVE: The present study examined the clinical and
      histopathological effects of a fractional 1550 nm erbium diode fiber laser in
      patients with bilateral moderate hand photodamage. METHODS: Nine subjects with
      Fitzpatrick skin types I-III, a mean age of 57 years with an average Fitzpatrick
      wrinkle score of 4.44 were entered in the present study. Five to six laser
      treatments were administered to each individual. Physician analysis based on a
      quartile improvement scale for wrinkling, pigmentation, skin texture and overall
      photodamage was assessed at 1-month, 3-month and 6-month follow-up visits. In
      addition, histological analyses (H&E) were carried out on three individuals.
      RESULTS: Each photodamage characteristic exhibited statistically significant
      improvement or better (23%) in overall photodamage at the 6-month follow-up
      visit. Histologic evaluation showed a reduction in atypical keratinocytes,
      improvement in rete ridge formations, increased collagen density and a reduction
      in solar elastosis at 6 months post-treatment. CONCLUSION: The present study
      demonstrates the potential of non-ablative fractional lasers for the treatment of
      non-facial anatomic areas such as the dorsum of the hands.

PMID- 19177258
TI  - Digit ratio (2D:4D) and hand preference for writing in the BBC Internet Study.
AB  - The ratio of the length of the second to the fourth digit (2D:4D) may be
      negatively correlated with prenatal testosterone. Hand preference has been linked
      with prenatal testosterone and 2D:4D. Here we show that 2D:4D is associated with
      hand preference for writing in a large internet sample (n>170,000) in which
      participants self-reported their finger lengths. We replicated a significant
      association between right 2D:4D and writing hand preference (low right 2D:4D
      associated with left hand preference) as well as a significant correlation
      between writing hand preference and the difference between left and right 2D:4D
      or Dr-l (low Dr-l associated with left hand preference). A new significant
      correlation between left 2D:4D and writing hand preference was also shown (high
      left 2D:4D associated with left hand preference). There was a clear interaction
      between writing hand preference and 2D:4D: The left 2D:4D was significantly
      larger than the right 2D:4D in male and female left-handed writers, and the right
      hand 2D:4D was significantly larger than the left hand 2D:4D in male and female
      right-handed writers.

PMID- 19177259
TI  - Repeat uterine artery embolization following poor results.
AB  - It was the objective of this study to assess the efficacy of repeat uterine
      artery embolization following lack of symptom relief from initial procedure. We
      performed a retrospective chart review of patients undergoing embolization for
      symptomatic uterine myomata between 1994 and 2007. Success was defined based upon
      responses to symptom-relief questionnaires. Patients who reported no relief or
      worsening of symptoms were offered repeat embolization as well as surgical
      intervention. Patients who elected to undergo repeat embolization were evaluated
      for success following the procedure. During the study period, 1058 patients
      underwent initial bilateral uterine artery embolization. Forty-two (3.97%)
      patients reported unsuccessful symptom relief. Thirty-nine patients who reported
      poor results underwent a second bilateral embolization. Thirty-four of these
      patients completed symptom-assessment questionnaires; thirty-two patients (94.1%)
      reported symptom relief lasting at least six months post-procedure. The vast
      majority of our patients who underwent a second embolization after initial poor
      results had successful symptom relief. Patients should be offered a second
      uterine artery embolization after a poor outcome.

PMID- 19177260
TI  - Chlamydia trachomatis genotypes associated with pneumonia in Chilean infants.
AB  - We determined the serovar distribution and genetic variability of the omp1 gene
      of C. trachomatis in nasopharyngeal aspirates from consecutive infants with
      pneumonia. C. trachomatis was detected by PCR in 17/94 (18.1%) specimens. Serovar
      E (47.1%) was the most frequent, followed by serovars F (17.6%), Ja (17.6%), D
      (11.8%), and G (5.9%). Nucleotide sequence analysis showed polymorphism of Omp1.

PMID- 19177261
TI  - Community acquired Staphylococcus aureus meningitis in adults.
AB  - We present 9 patients with community acquired Staphylococcus aureus meningitis.
      Foci of infection outside the central nervous system were present in 8 (89%)
      patients, mostly endocarditis and pneumonia. Cardiorespiratory complications
      occurred frequently and 6 patients died (67%). Identification and treatment of
      the primary focus of infection should be a priority in these patients.

PMID- 19177262
TI  - Lack of association between beta 2-adrenergic receptor polymorphisms and juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a chronic autoimmune
      arthropathy. Beta 2-adrenergic receptors are a link between the sympathetic
      nervous system and the immune system. Associations between variants in the gene
      encoding the beta 2-adrenergic receptor (ADRB2) and autoimmune disorders such as
      rheumatoid arthritis (RA) have been demonstrated. We aimed to investigate ADRB2
      variants for association with JIA. METHODS: Genotypes and haplotypes of two ADRB2
      variants (G16R and Q27E) were determined in 348 children with JIA and 448 healthy
      controls by direct molecular haplotyping using melting-curve analysis of a
      fluorescently labelled loci-spanning probe. Case-control analysis was performed
      to investigate whether ADRB2 variants were associated with JIA. RESULTS: No
      association was found between JIA and alleles, genotypes, or haplotypes of ADRB2.
      Specifically, the haplotype that demonstrated a strong association with RA
      (R16/Q27) was not associated with JIA. None of the variants demonstrated
      association after stratification by JIA subtypes or gender. CONCLUSIONS: Our
      results indicate that ADRB2 variants are not associated with JIA or any of the
      major JIA subtypes. These observations suggest that, although they share several
      clinical and pathological features, JIA and RA have unique genetic associations.

PMID- 19177263
TI  - Magnetic resonance imaging in the assessment of metacarpophalangeal joint disease
      in early psoriatic and rheumatoid arthritis.
AB  - OBJECTIVES: The aim of this study was to determine whether magnetic resonance
      imaging (MRI)-related entheseal changes including osteitis and extracapsular
      oedema could be used to differentiate between metacarpophalangeal (MCP) joint
      involvement in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS:
      Twenty patients (10 each with early RA and PsA) had dynamic contrast-enhanced MRI
      (DCE-MRI) of swollen MCP joints. Synovitis and tenosynovitis was calculated using
      quantitative analysis including the degree and kinetics of enhancement of
      gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Periarticular bone
      erosion and bone oedema were scored using the Outcome Measures in Rheumatology
      Clinical Trials (OMERACT) proposals. Entheseal-related features including
      extracapsular soft tissue enhancement or regions of diffuse bone oedema were also
      evaluated. RESULTS: MRI was not able to differentiate at the group level between
      both cohorts on the basis of entheseal-related disease but a subgroup of PsA
      patients had diffuse extracapsular enhancement (30%) or diffuse bone oedema
      (20%). The RA patient group had a greater degree of MCP synovitis (p<0.0001) and
      tenosynovitis than PsA patients (p<0.0001). There were no significant differences
      in either the total number of erosions (p = 0.315) or the presence of
      periarticular bone oedema (p = 0.105) between the groups. CONCLUSION: Although
      conventional MRI shows evidence of an enthesitis-associated pathology in the MCP
      joints in PsA, this is not sufficiently common to be of diagnostic utility.

PMID- 19177264
TI  - Expression of the class I interferon-related MxA protein in temporal arteries in
      polymyalgia rheumatica and temporal arteritis.
AB  - OBJECTIVE: The aim of this study was to assess the expression of the interferon
      type I (IFN-I)-associated MxA protein in polymyalgia rheumatica (PMR) and
      temporal arteritis (TA). METHODS: Non-inflamed temporal artery biopsies from 11
      PMR patients were compared with biopsies from 13 patients given other diagnoses.
      Coded sections were screened immunocytochemically for MxA protein, CD83, CD68,
      CD3, and S100 protein. Inflamed temporal artery biopsies from four patients with
      TA were also investigated. RESULTS: Focal MxA expression was seen in non-inflamed
      arteries, more frequently in PMR than in controls (p = 0.0124). MxA expression
      was also more common in adventitial dendritic cells (DCs) in PMR (p = 0.0124).
      Activated adventitial DCs were detected in PMR. Focal MxA expression in the
      inflamed biopsies from the patients with TA was not related spatially to the
      inflammation. CONCLUSIONS: The expression of MxA protein in arteries from
      patients with PMR and TA shows that non-inflamed and inflamed vessel walls are
      influenced by IFN-I. Further studies are required to elucidate whether IFN-I
      plays a role in the initiation of PMR and/or TA, serving as a link between the
      innate and the adaptive immune responses, as in some other autoimmune disorders.

PMID- 19177265
TI  - The regulatory role of nerve growth factor and its receptor system in fibroblast
      like synovial cells.
AB  - OBJECTIVES: Investigating the role of nerve growth factor (NGF) and its receptors
      (NGF-R) in inflammatory diseases is an active field of research. Inflammatory
      diseases of the joint are the commonest cause of human morbidity but very little
      is known about the effect of NGF on synovial tissue biology. Here we have studied
      NGF/NGF-R and their functional significance on cultured fibroblast-like synovial
      cells (FLS) collected from the synovial tissue of five healthy subjects. METHODS:
      NGF/NGF-R expression was determined in the basal condition and after stimulation
      with tumour necrosis factor (TNF)alpha and interleukin (IL)-1beta by enzyme
      linked immunosorbent assay (ELISA) and fluorescence-activated cell sorting
      (FACS). Proliferation studies were performed by cell count, hexosaminidase assay,
      and the MTT assay. The synovial fluid (SF) NGF level was studied by ELISA in 12
      psoriatic arthritis (PsA), 14 rheumatoid arthritis (RA), and 10 osteoarthritis
      (OA) patients. RESULTS: FACS studies showed that unstimulated FLS expressed low
      levels of NGF and the high-affinity NGF-tyrosine kinase receptor TrkA, and
      TNFalpha and IL-1beta increased NGF and TrkA expression in FLS. NGF (100 ng/mL)
      increased FLS proliferation by 400% compared to the control (medium only). The
      NGF level was significantly higher in the PsA group (365.5+/-85.2 pg/mL) than in
      the RA (120+/-35 pg/mL) and OA groups (30+/-6 pg/mL). CONCLUSIONS: Upregulation
      of NGF/TrkA in proinflammatory cytokine-activated FLS, the mitogenic effect of
      NGF on FLS, and the increased NGF level in SF of inflammatory arthritis suggest
      that there is cross-talk between NGF/NGF-R and FLS. These results also suggest
      that dysregulated production of NGF may lead to synovial cell proliferation and
      thus could influence the inflammatory and proliferative cascades of inflammatory
      arthritis.

PMID- 19177266
TI  - Association between ankylosing spondylitis and polymorphism of tumour necrosis
      factor receptor II in Taiwanese patients.

PMID- 19177267
TI  - The politics of technicians.
AB  - An unintended consequence of the New York psychology Scope of Practice
      legislation led to a restriction in the use of testing technicians that has yet
      to be reversed after 4 years. The misperception of neuropsychology by state
      legislators and psychology colleagues was a key obstacle to achieving a timely
      solution. We discuss how the political agenda and practice philosophies of New
      York neuropsychologists were at odds with those of our psychology colleagues, and
      how that brought about a protracted struggle affecting both patient care and the
      practice of clinical neuropsychology. Neuropsychologists must maintain an active
      role in professional and political organizations with equal attention at the
      local, state, and national levels to avoid similar restrictions to their clinical
      practice.

PMID- 19177268
TI  - Incidence, sources, and self-management of depression in persons attending a
      rural health clinic in southeastern North Carolina.
AB  - The purpose of this study was to determine the incidence, sources, and self
      management strategies of depression in a sample of 48 persons visiting a primary
      care clinic in rural Southeastern North Carolina. Forty percent of the
      participants met the criteria of clinical depression on the Center for
      Epidemiological Studies Depression Scale (CES-D). Highest rates of depression
      found in single, African American men who were employed with adequate health
      insurance were attributed primarily to work related stressors in dealing with
      overwhelming social problems of other rural residents, as well as economic
      stressors. Critical incident interviews identified depression self-management
      strategies and sources of social support.

PMID- 19177269
TI  - Community-based perceptions of neighborhood health in urban neighborhoods.
AB  - This community-based study explored perceptions of neighborhood health and
      neighborhood health characteristics to inform a new urban health neighborhood
      outreach program utilizing nurse and community health worker teams. Neighborhood
      residents and representatives from community agencies described their perceptions
      of personal health and neighborhood health through questionnaires and focus
      groups called community conversations. Respondents were more likely to report
      themselves as healthy and less likely to report their neighborhoods as healthy.
      Community conversations' common themes included respect, partnerships and
      relationships. Results provide guidance for planners of urban neighborhood health
      initiatives.

PMID- 19177270
TI  - Public health nurses' primary health care practice: strategies for fostering
      citizen participation.
AB  - Citizen participation is heralded as a critical element of community health
      programs that emphasize empowerment and health promotion strategies. Although
      there is a growing body of research on public health nurses' primary health care
      practice, few studies have described how public health nurses foster citizen
      participation. This article presents findings from an interpretive qualitative
      study of public health nurses' perceptions of their role in fostering citizen
      participation in an eastern Canadian province at a time of significant health
      care restructuring. The findings from this study clearly profile public health
      nurses as integral to the practice of fostering citizen participation.

PMID- 19177271
TI  - Community-based participatory research in developing an obesity intervention in a
      rural county.
AB  - This research includes a study of body mass index (BMI) measurement for 11-year
      old students (n = 174) within a rural county during the 2005-2006 academic year.
      School entry assessments were used to determine students' individual BMIs
      longitudinally and determine prevalence of risk of overweight (weighted for
      gender and age). Results were provided to county school districts and
      communities, which used the data to determine policy and curriculum changes
      related to school wellness program planning and development, develop wellness
      activities, and pursue funding support. This study has implications for data
      collection and school health program development within a rural setting.

PMID- 19177284
TI  - [Intravascular displacement of a StarClose device after brachial artery
      puncture].

PMID- 19177273
TI  - Concentrations of bioaerosols, odors, and hydrogen sulfide inside and downwind
      from two types of swine livestock operations.
AB  - Few data on in-barn and downwind concentrations of endotoxin, bioaerosols, and
      odors from livestock facilities are available, and no studies have compared
      conventional confinement operations with the more animal-friendly hoop
      operations. Hoops are open to the environment and use a composted bedding system
      rather than housing pigs on slatted floors over pits holding manure slurry as in
      conventional confinements. We assessed airborne toxicants upwind, in barns, and
      downwind and evaluated determinants of exposure. Inhalable particulate matter,
      endotoxin, odor threshold, hydrogen sulfide, culturable mesophilic bacteria,
      culturable fungi, and total airborne microbes, along with wind speed,
      temperature, and humidity were measured at separate midsized livestock facilities
      (one hoop, one confinement) in Central Iowa on 10 occasions over 2 years.
      Significant differences in contaminants were observed between hoops and
      confinement buildings and across seasons for endotoxin, odors, airborne
      microorganisms, and hydrogen sulfide. For hoops and confinements, respectively,
      geometric mean in-barn concentrations were 3250 and 3100 EU/m(3) for endotoxin;
      1400 and 1910 microg/m(3) for particulates; 19.6 and 146 ppb for hydrogen
      sulfide; 137 and 428 dilutions for odor threshold; and 3.0 x 10(6) and 1.5 x
      10(6) organisms/m(3) for total microbes. Endotoxin, odor, and culturable
      microorganisms exceeded recommended exposure limits. Reduced analysis of variance
      models for these contaminants demonstrated differences by barn type, season,
      number of pigs, and, in some cases, temperature and humidity. Both types of swine
      operations produced high airborne concentrations of endotoxin, odor, hydrogen
      sulfide, bacteria, and fungi. Endotoxin and odors were found downwind at
      concentrations previously associated with adverse health effects.

PMID- 19177286
TI  - Do we need a cancer screening in patients with idiopathic deep vein thrombosis?
AB  - AIM: To review the literature concerning the need for a cancer screening battery
      to diagnose a hidden cancer in patients presenting with idiopathic venous
      thromboembolism (VTE). MATERIALS AND METHODS: Data from computerized database
      programs (Medline, Ovid) was retrieved. A review of the literature regarding
      studies on cancer screening in patients with idiopathic VTE was performed and our
      own policy included. RESULTS: Patients with VTE have a higher rate of malignancy
      which may still be undiagnosed. During follow-up of patients with idiopathic VTE,
      the incidence of cancer increases and is more likely associated with a worse
      prognosis. Limited diagnostic work-up in patients with idiopathic VTE allows the
      diagnosis of a hidden malignancy in about half of the cases with a sensitivity of
      48 %. Extensive screening of cancer with idiopathic VTE allows less of a delay
      and earlier stage at diagnosis with a 93 % sensitivity. However, reduced cancer
      related mortality is not statistically significant. A two-fold fatal PE and more
      than 3-fold fatal bleeding are registered in VTE patients with hidden cancer
      compared to patients without cancer. The major risk factors for hidden cancer are
      old age, anemia, idiopathic and bilateral deep vein thrombosis. CONCLUSION: There
      is no consensus regarding the benefit of extensive screening in patients
      presenting with idiopathic VTE. Clear diagnostic work-up guidelines are not yet
      available. A cost-effective diagnostic algorithm for cancer screening in patients
      with idiopathic VTE is needed.

PMID- 19177287
TI  - [Sonographic localization of non-palpable implanon hormone implants].
AB  - PURPOSE: Implanon is a rod-shaped hormone implant which leads to reliable
      contraception. The rod is implanted in the subcutis of the upper arm and is
      usually removed easily after its effective period. In the scenario where the rod
      is not palpable, the removal of the rod can be difficult or impossible. The
      purpose of this study was to evaluate the reliability of US in locating non
      palpable Implanon implants and to investigate the optimal technical parameters
      for determining the location. MATERIALS AND METHODS: In a prospective study we
      evaluated 21 women between June 2004 and June 2008. In 14 patients previous
      examinations with US, radiography, CT and/or MRI were non-diagnostic. The US
      evaluation followed a standardized protocol in transverse and longitudinal
      sections. The technical parameters US frequency, position and number of focal
      zones and compound imaging were varied to define the optimal parameters for the
      visualization of the Implanon implant. RESULTS: The Implanon implant was detected
      in all 21 patients. Reasons for negative palpability were mainly an intramuscular
      or subfascial location as well as a significant migration of the Implanon implant
      in 2 patients. The use of a high US frequency, the position of the focal zones in
      the near field and the deactivation of compound imaging all facilitate
      visualization of the characteristic US morphology of the plastic rod. CONCLUSION:
      High resolution US is the method of choice for determining the location of non
      palpable Implanon implants. Knowledge of US morphology and optimal technical
      settings as well as the use of high-resolution scan heads are essential for
      determining the correct location.

PMID- 19177288
TI  - The use of contrast-enhanced ultrasound in patients with GIST metastases that are
      negative in CT and PET.

PMID- 19177289
TI  - Trimodality imaging of colonic lymphoma.

PMID- 19177290
TI  - Retrograde dilatation via gastrostomy of a proximal esophagoileal anastomotic
      stricture in an infant with esophageal atresia.

PMID- 19177291
TI  - A simple hands-off method for converting a biliary drain from mouth to nose.

PMID- 19177292
TI  - Large intramural colonic hematoma after polypectomy.

PMID- 19177293
TI  - Use of a self-expandable metallic stent for large bile leakage following
      orthotopic liver transplant.

PMID- 19177294
TI  - Endoscopic ultrasound-guided fine needle aspiration diagnosis of extramedullary
      hematopoiesis in mediastinum.

PMID- 19177306
TI  - [90th German Radiology Congress -- one brings the seemingly unfeasible to maximum
      feasibility].

PMID- 19177307
TI  - [Board elections for the working group of the DRG].

PMID- 19177309
TI  - [DRG-members -- cost-free membership in the ESR].

PMID- 19177310
TI  - [No obligation to remain silent through the presentation of the radiology journal
      from the Dr.'s office].

PMID- 19177311
TI  - [New executive board in the ORG].

PMID- 19177312
TI  - Cardiac injury markers in non-elite marathon runners.
AB  - An elevation of cardiac injury markers including creatinine kinase (CK),
      myoglobin (Myo) and cardiac troponin T (cTnT) has been observed in elite athletes
      following strenuous exercise. The mechanism and significance of this observation
      however have not been fully elucidated. The goals of this study were: 1) to
      determine whether these changes in biomarkers also occur in a large,
      heterogeneous group of non-elite athletes; and 2) to identify possible clinical
      or biochemical associations. We recruited 129 non-elite runners in 2006, 61
      individuals who were taking part in the half (13.1 miles) marathon and 68
      individuals participating in the full (26.2 miles) marathon. Demographic data and
      blood samples were collected for analysis of CK, Myo, cTnT, and Creatinine (Cr)
      levels within two hours of race start, at race completion, and 1-h post-race for
      both patient cohorts. In the 61 individuals (40 males, 40+/-12 yrs) completing
      the half marathon in a mean time of 150+/-20 min, 90.3%, 65.2%, and 30.6% of the
      subjects exhibited significant elevations in Myo, CK, and cTnT, respectively
      immediately post race and 100%, 74.9% and 45.9% in the same biomarkers one hour
      post race. In the 68 individuals (44 males, 42+/-14 yrs) completing the full
      marathon in a mean time of 310+/-30 min, 95.3%, 70.2% and 35.7% exhibited
      significant elevations in Myo, CK and cTnT respectively immediately post race and
      100%, 78.5% and 52.8% in the same biomarkers one hour-post race. The elevation in
      cTnT levels post-race were modestly associated with the time required to complete
      the race for the entire cohort of marathon runners. The serum levels of Cr, CK,
      and Myo post-race did not correlate however with age, sex, BMI, level of
      training, or prior marathon experience. Elevations of cardiac injury markers in
      non-elite athletes are extremely common following the completion of endurance
      events and correlate to the increased endurance time. Whether the increase in the
      levels of these enzymes represents true myocardial injury or a result of the
      release of cTnT from the myocytes requires further investigation.

PMID- 19177313
TI  - Identification of darbepoetin alfa in human plasma by liquid chromatography
      coupled to mass spectrometry for doping control.
AB  - Darbepoetin alfa (DPO) or Novel Erythropoiesis Erythropoiesis Stimulating Protein
      (NESP), an analog of recombinant human erythropoietin (rhEPO), is abused as a
      blood doping agent along with the latter in human sports. This paper describes a
      new method for unequivocal identification of DPO in human plasma. The analyte was
      extracted from plasma by immunoaffinity separation with anti-rhEPO antibodies,
      digested by trypsin followed by PNGase F, and analyzed by liquid chromatography
      coupled to tandem mass spectrometry. The deglycosylated tryptic peptide, T (9),
      was employed in DPO identification using liquid chromatographic retention time
      and major product ions of the T (9) peptide. The limit of detection of this
      method for DPO was 0.1 ng/mL in plasma, and that of identification was 0.2 ng/mL.
      This method is definitive and devoid of false positive results, providing "mass
      fingerprints" for identification of DPO in human plasma samples. Although this
      method is not applicable to identification of rhEPO in human plasma because it
      cannot differentiate rhEPO from endogenous EPO, it is the first successful
      attempt towards establishing a reliable and selective method for definitive
      identification of exogenously administered EPOs in doping control analyses.

PMID- 19177314
TI  - Effects of acute hypoxic exposure on prooxidant/antioxidant balance in elite
      endurance athletes.
AB  - We investigated whether acute hypoxic exposures could modify the pro
      oxidant/antioxidant balance in elite endurance athletes, known to have efficient
      antioxidant status. Forty-one elite athletes were subjected to two hypoxic tests:
      one at an altitude of 4 800 m during 10-min of mild exercise (4 800 m test) and
      the second at rest for 3 h at an altitude of 3 000 m (3 000 m test). Plasma
      levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA),
      ferric reducing antioxidant power (FRAP) and lipid-soluble antioxidants were
      measured before and immediately after the 4 800 m test and at the end of the 3
      000 m test. The 4 800 m and the 3 000 m tests induced a significant increase in
      the level of MDA and AOPP (+7.1% and +71.7% for 4 800 m test and +8.6% and +40.9%
      for 3 000 m test). The changes in plasma MDA and arterial oxygen saturations were
      significantly correlated (r=0.35) during the 3 000 m test. FRAP values (-13%) and
      alpha-tocopherol (-21%) were decreased following the 3 000 m test. However,
      following the 4 800 m test, only alpha-tocopherol was decreased (-16%). These
      results provide evidence that the highly-trained athletes do not have the
      antioxidant buffering capacity to counterbalance free radical over-production
      generated by acute hypoxic exposure, with or without mild exercise.

PMID- 19177315
TI  - Accuracy of the Velotron ergometer and SRM power meter.
AB  - The purpose of this study was to determine the accuracy of the Velotron cycle
      ergometer and the SRM power meter using a dynamic calibration rig over a range of
      exercise protocols commonly applied in laboratory settings. These trials included
      two sustained constant power trials (250 W and 414 W), two incremental power
      trials and three high-intensity interval power trials. To further compare the two
      systems, 15 subjects performed three dynamic 30 km performance time trials. The
      Velotron and SRM displayed accurate measurements of power during both constant
      power trials (<1% error). However, during high-intensity interval trials the
      Velotron and SRM were found to be less accurate (3.0%, CI=1.6-4.5% and -2.6%, CI=
      3.2--2.0% error, respectively). During the dynamic 30 km time trials, power
      measured by the Velotron was 3.7+/-1.9% (CI=2.9-4.8%) greater than that measured
      by the SRM. In conclusion, the accuracy of the Velotron cycle ergometer and the
      SRM power meter appears to be dependent on the type of test being performed.
      Furthermore, as each power monitoring system measures power at various positions
      (i.e. bottom bracket vs. rear wheel), caution should be taken when comparing
      power across the two systems, particularly when power is variable.

PMID- 19177316
TI  - Dynamic stretching and golf swing performance.
AB  - The aim of the present study was to examine the effect of dynamic stretching,
      static stretching and no stretching, as part of a general warm-up, on golf swing
      performance with a five-iron. Measures of performance were taken 0 min, 5 min, 15
      min and 30 min after stretching. Dynamic stretching produced significantly
      greater club head speeds than both static stretching (Delta=1.9m.s (-1); p=0.000)
      and no stretching (Delta=1.7 m.s (-1); p=0.000), and greater ball speeds than
      both static stretching (Delta=3.5m.s (-1); p=0.003) and no stretching
      (Delta=3.3m.s (-1); p=0.001). Dynamic stretching produced significantly
      straighter swing-paths than both static stretching (Delta=-0.61 degrees ,
      p=0.000) and no stretching (Delta=-0.72 degrees , p=0.01). Dynamic stretching
      also produced more central impact points than the static stretch (Delta=0.7 cm,
      p=0.001). For the club face angle, there was no effect of either stretch or time.
      For all of the variables measured, there was no significant difference between
      the static stretch and no stretch conditions. All of the results were unaffected
      by the time of measurement after stretching. The results indicate that dynamic
      stretching should be used as part of a general warm-up in golf.

PMID- 19177317
TI  - [New developments in minimally invasive urology: NOTES (Natural Orifice
      Transluminal Endoscopic Surgery) and LESS (Laparo-Endoscopic Single-Site Surgery)
      in urology].
AB  - Laparoscopic surgery in urology has undergone a rapid development in the last
      decade. In general, many studies have underlined the benefits of laparoscopy in
      urology. The latest innovations in the field of minimally invasive urology are
      aimed at a further reduction of the morbidity associated with minimally invasive
      surgery. Two novel innovations are currently being developed, natural orifice
      transluminal endoscopic surgery (NOTES), whereby intraperitoneal access is gained
      through natural orifices and laparo-endoscopic single-site surgery (LESS),
      wherein one surgical access is used both for introducing instruments and for
      retrieving the specimen. Many case reports and small patient series have been
      published rapidly in the past two years. However, comparative randomised studies
      to conventional laparoscopy or open surgery do not yet exist. LESS and NOTES are
      two new innovative approaches, whereby feasibility studies not only for simple
      nephrectomy but also for complex procedures like partial nephrectomy, radical
      prostatectomy, ureterocystoneostomy have been published. In the next few years,
      comparative studies between these techniques and conventional laparoscopy can be
      expected.

PMID- 19177318
TI  - [Interdisciplinary recommendations for the treatment of metastatic renal cell
      carcinoma].
AB  - With the introduction of targeted therapies, a paradigm shift for the treatment
      of metastatic renal cell cancer has taken place. New compounds like sunitinib,
      sorafenib, bevacizumab and temsirolimus have become established as new
      therapeutic standards. An interdisciplinary consensus conference was held to
      discuss treatment sequences and open questions. Results from the 2007 conference
      provided the basis for the 2008 meeting. The results of the 2008 conference are
      presented as short theses.

PMID- 19177320
TI  - [Tomatoes and lycopene in prevention and therapy--is there an evidence for
      prostate diseases?].
AB  - Tomatoes are discussed to have an important role in the prevention of and therapy
      for prostate cancer (PCA). Whether or not they are also useful in the primary and
      secondary prevention of benign prostate hyperplasia (BPH) is not clear. This
      review summarises the results of original contributions with a focus on
      interventional studies. Whereas epidemiological studies on BPH prevention provide
      no evidence for a preventive potential of tomatoes and tomato products, the
      majority of interventional trials points to an increased DNA resistance against
      oxidative-induced damage. Even though their effect on a surrogate marker of the
      IGF pathway cannot be evaluated so far due to insufficient data, the consumption
      of tomatoes and tomato products may probably protect from PCA--at least when
      considering low-grade PCA. Thus, regular consumption of these foods can be
      recommended for the prevention of PCA. Tomato products might also be useful in
      the therapy for BPH and PCA. The intake of isolated lycopene does not protect
      from the development of PCA. However, in the doses achieved by consumption of
      tomato products, lycopene ingestion might also be effective in PCA therapy.

PMID- 19177319
TI  - [Medical treatment of metastatic renal cell carcinoma after the approval and
      market entry of multitargeted tyrosine kinase inhibitors in Germany].
AB  - PURPOSE: To describe the current use and administration of multitargeted tyrosine
      kinase inhibitors (sunitinib and sorafenib) in the management of metastatic renal
      cell carcinoma (RCC) and to characterise frequent adverse events. MATERIALS AND
      METHODS: A questionnaire was sent to 104 urologists and medical oncologists
      having their own practice. The common use of medical treatment with sunitinib and
      sorafenib in patients with metastatic RCC was recorded. Data on the most frequent
      drug-associated adverse events were registered and described in a preliminary
      patient cohort. RESULTS: Medical oncologists in private practice treat over twice
      as many patients with metastatic RCC (8/year) as established urologists. Most
      medical oncologists but not urologists already use multitargeted tyrosine kinase
      inhibitors. For the initiation of treatment, most urologists admit patients to a
      hospital, whereas medical oncologists start and carry out medical treatment
      themselves. In all patients adverse events occurred due to medical treatment,
      leading to therapy stop or pause in 53% of patients. The most frequent adverse
      events were abnormal fatigue, arterial hypertension, diarrhoea and the hand-foot
      skin syndrome. CONCLUSIONS: Multitargeted tyrosine kinase inhibitor therapy in
      Germany is currently done predominantly by medical oncologists rather than
      urologists. Adverse events caused by sunitinib and sorafenib frequently required
      medical care, and in our initial series of patients prompted physicians to pause
      treatment.

PMID- 19177321
TI  - [Chylous ascites after laparoscopic nephroureterectomy].
AB  - A 65-year-old man underwent a laparoscopic nephroureterectomy with a radical
      retroperitoneal lymphadenectomy for transitional cell carcinoma in the pyelon of
      the left kidney associated with a paraaortal lymphadenopathy. Four weeks later
      the patient presented with weight loss, a distended abdomen and a swelling of the
      left hemiscrotum. With increasing complaints and the suspicion of a large
      lymphocele an exploratory laparoscopy with the possibility of a fenestration was
      performed. Intraoperatively the laparoscopy revealed a chylous ascites but failed
      to detect an injury to the lymph system and a localised leak. The ascites
      eventually resolved under a strict dietary regimen with a medium-chain
      triglyceride-based diet and repeated long-term drainage. We report this case to
      encourage a multimodal approach in this potentially fatal complication.

PMID- 19177322
TI  - ["Single incision" -- nephroureterectomy with transurethral ureter stripping].

PMID- 19177323
TI  - [Coincidence of adenocarcinoma and MALT lymphoma of the prostate--first report].
AB  - INTRODUCTION: First description of a prostate adenocarcinoma coinciding with the
      rare MALT lymphoma of the prostate. CASE REPORT: 68-year-old patient with a pT2c,
      pN0, M0, Gleason 3 + 3 prostate carcinoma (retropubic radical prostatectomy with
      pelvic lymphadenectomy) and systemic indolent MALT lymphoma of the prostate (bone
      marrow biopsy). Therapy and course are described and further explained by
      referring to case reports found in the literature. In this context, possible
      pathogenetic mechanisms, the prognosis for this special disease and possible
      therapeutic approaches are discussed. CONCLUSION: MALT lymphomas of the prostate
      are rare, and so far a coincidence with a prostate carcinoma is unprecedented.
      The prostate carcinoma is treated according to stage, while the MALT lymphoma is
      managed according to individual treatment strategies. The histopathological
      classification is more important for the prognosis. Treatment with antibiotics to
      eradicate possible copathogenic Helicobacter pylori is discussed as an innovative
      therapeutic approach. The pathogenesis of the MALT lymphoma of the prostate
      cannot yet be clarified definitively according to a literature review.

PMID- 19177324
TI  - [On the role of pharmacists in the care of patients with depressive disorders-
      evaluation of a training programme for pharmacists].
AB  - Depressive disorders are highly prevalent, under-diagnosed and under-treated,
      causing high direct and socioeconomic costs. So far, the role of pharmacists in
      counselling and supervision of patients with depression has hardly been
      investigated. However, as pharmaceutical experts for doctor's prescriptions as
      well as self-medication, they represent an important multiplicator group in
      health care systems. The aim of nationwide seminars for pharmacists was to
      improve attitudes and knowledge of the spectrum of depressive disorders. The
      evaluation (n=102) which was performed within the seminars shows that personal
      beliefs of pharmacists regarding depression depend on their own age and years of
      professional experience. The study points out that specific training programmes
      (e. g., communication techniques), especially in a subgroup of younger and less
      experienced staff members in the pharmacy, may improve the care of depressive
      individuals. This should--in close cooperation with general practitioners, mental
      health specialists and health care systems--also substantially contribute to
      enhance effectiveness of treatment of depressive disorders and to reduce
      healthcare costs.

PMID- 19177326
TI  - [Statutory ambulatory medical care through the eyes of the health insurance
      beneficiaries--methods and results of the 2006 NASHIP Health Insurance
      Beneficiary survey: care utilisation, primary care, and emergency medical
      services].
AB  - OBJECTIVE: The aim of this study was to obtain valid information on the delivery
      of ambulatory medical care from the point of view of the health insurance
      beneficiaries. The National Association of Statutory Health Insurance Physicians
      (NASHIP) conducted in 2006 for the first time a nationally representative
      telephone survey. The survey set out to gather information on health care
      utilisation, patients' experiences and satisfaction with care delivery, and to
      provide an indication for the further development of the services offered.
      METHODS: Between 22 May and 8 June 2006, a random sample of 4 315 inhabitants
      from 18 to 79 years of age was interviewed using a computer-assisted telephone
      interview (CATI). The questionnaire included 51 questions relating to six topics,
      and consisted of a core set of questions and supplementary questions dealing with
      further details or special issues. One section of the 2006 survey focused on
      emergency medical services. In the analysis, samples were weighted to reflect the
      distribution of the population by age and sex. RESULTS: 82% of survey
      participants have visited a doctor's office in the last 12 months, and 93%
      indicated to have a regular general practitioner (GP) they consult for medical
      problems or health advice. Referring to all respondents, the mean number of
      consultations in a doctor's office was about 5 per year. Over 90% of respondents
      having a regular GP arrive at the office within 20 min, and for 61% home visits
      by their regular doctor are very important or important. 90% of respondents
      having seen the GP during the last 12 months assess the medical care received as
      very good or good. The places contacted when the regular office is closed are
      clearly varying by region and respondent's age. Whereas younger people primarily
      consult the hospital emergency department, the importance of the general
      practitioner in the case of an emergency increases with age. Overall, 29%
      preferentially turn to a hospital or hospital emergency department, another 25%
      to outpatient emergency medical services, and scarcely 16% to their regular GP.
      61% of survey participants or their close relatives have already utilised
      emergency medical services (EMS). Regarding the last case of a medical emergency,
      in 3 out of 5 cases patients went themselves to the emergency service. A total of
      74% of patients assess the care received by the emergency medical service as very
      good or good. Evaluations are less favourable in the event of prolonged waiting
      time for the emergency medical doctor at home or in the EMS office. CONCLUSION:
      The NASHIP health insurance beneficiary survey reflects a broadening patient and
      service orientation and provides valid information on ambulatory medical care
      through the eyes of the insurance beneficiaries. The survey depicts high overall
      satisfaction with primary care, a high degree of trust in the doctor's medical
      competence, and easily accessible services. Patient evaluations of outpatient
      emergency medical care are mainly positive, but still show room for improvement.

PMID- 19177325
TI  - [An economic organisation analysis of the need for the exchange of information
      between the European health systems].
AB  - BACKGROUND AND GOAL: Demographic development and technological progress are
      rapidly changing the existing health systems in Europe. As a result, increasingly
      more complex and heterogeneous structures are emerging, which clearly differ in
      each of the European member state. From a company's point of view these
      continuously changing frameworks are leading to an increasing non-transparency
      regarding the structures and processes within the healthcare systems themselves.
      The goal is to design a suitable solution to overcome the obstacles within the
      information exchange process between the individual European health systems.
      METHODS: Theoretic-deductive analysis was used for the design of an
      organisational structure that enables information transparency between the
      individual European health systems. Incorporation of an economic perspective was
      implemented under consideration of the theory for the building of the new
      institutional economics. RESULTS: The operational organisation analysis proves
      that the matrix project organisation with a function- and project-related
      decision system is the theoretically optimal organisational form. DISCUSSION AND
      CONCLUSION: The organisation model derived from the theoretical analysis offers
      an organisation variant that guarantees an optimal processing of tasks pertaining
      to European health systems. This could result in the closing of an existing
      supply gap in the knowledge market for health systems. The evaluation of
      enterprise practice and the comparison with existing departments in enterprises
      can be explored in further research work.

PMID- 19177327
TI  - [Role of minimal invasive surgery for primary and secondary hyperparathyroidism].
AB  - BACKGROUND: The standard surgical approach to treat primary (pHPT) and secondary
      hyperparathyroidism (sHPT) used to be a cervicotomy with exploration of all four
      parathyroid glands. This access has been challenged recently by the introduction
      of minimally invasive techniques in order to achieve superior cosmesic results
      and to reduce theatre time. We analyzed the advantages and morbidities of these
      surgical aproaches. PATIENTS AND METHODS: Between 1997 and 2006 a total of 123
      patients (109 with pHPT and 14 with sHPT) underwent parathyroidectomy at the ENT
      Department in Luzern. Ultrasonographic scanning was performed on 74 patients
      (68%), szintigraphy in 8 patients (7%) and both scanning methods in 27 patients
      (25%). 103 patients were available for follow-up. The indications for each
      technique were reviewed and outcome measures included serum Calcium and
      parathyroid hormone levels. RESULTS: Sensitivity for preoperative
      ultrasonographic and scintigraphic scanning was 67% and 65% for identification of
      the correct quadrant and 74% and 71% for identification of the correct side. A
      bilateral exploration was performed until June 2001 for all patients. Thereafter,
      a minimally invasive approach was chosen for patients with pHPT, whereas patients
      with sHPT still require bilateral exploration. Adequate preoperative localization
      was a prerequisite for a minimally invasive technique. Mean postoperative serum
      Kalzium levels were within the normal range, independently of the surgical
      technique and disease. Two patients developed hypercalcemia after an initially
      successful operation. CONCLUSIONS: Review of the literature confirms the shift
      from bilateral exploration towards minimally invasive techniques. The incidence
      of persistent or recurrent disease as well as the rate of complications seems
      comparable. Operation time for minimally invasive techniques is reduced in the
      hands of an experienced surgeon. However, proper preoperative localization of the
      diseased parathyroid gland is not always possible and the expenses of
      intraoperative parathyroid hormone measures do not lower the overall costs.
      Considerable experience and a multidisiplinary approach (endocrinologist,
      surgeon, pathologist) is required to adopt efficient minimally invasive
      techniques. As for sHPT, bilateral exploration remains the treatment of choice.

PMID- 19177328
TI  - [Investigations of nasal deposition efficiency of wheaten flour and corn starch].
AB  - BACKGROUND: In-vivo-evaluation of the nasal deposition efficiency is problematic,
      because a postnasal measurement of the dust particle concentration is difficult.
      A new method is represented, which measures in front of the nose the dust loading
      after ortho- and retronasal passage relative easily. METHODS: 36 healthy subjects
      were nasally dust-exposed sitting in an exposure chamber. With the help of dust
      sampling system (Respicon) the particle size-referred dust loading before and
      after the nasal airflow passage was gravimetrically determined. The constant flow
      rate was 3.111 per minute. A contamination with breathing air was excluded by an
      active velopharyngeal closure. The subjects breathed orally over a breathing tube
      clean air. They were in each case 15 min exposed to the constant pre-nasal
      wheaten flour or corn starch dust produced over a brush disperser (Palas, RBG
      1000). The time interval between both exposures was seven days excluding cross
      over effects. RESULTS: The deposition efficiency of both types of food powder was
      particle size dependent. Highest it was -as expected- with the particle sizes
      between 5-100 microm. Here it lay between 92% and 99%. The small particles of
      wheaten flour respective corn starch with an aerodynamic diameter between 1-4
      microm deposited nasally 31% respectively 74%. CONCLUSIONS: The new relatively
      simple method of measurement of nasal deposition efficiency does not load the
      deeper respiratory tract. The results confirm the good filtering capability of
      the healthy nose for large dust particles. The nasal deposition of particles
      smaller than 5 microm is reduced but not absent. The small dust particles of
      wheaten flour and corn starch are very different nasally deposited. The different
      electrostatic charges of the two food powders may explain these differences.

PMID- 19177330
TI  - Demonstration of 1-year duration of immunity for attenuated Bordetella
      bronchiseptica vaccines in dogs.
AB  - Three groups of healthy dogs with low antibody titers to Bordetella
      bronchiseptica (Bb), canine parainfluenza virus (CPI), and canine adenovirus type
      2 (CAV-2) were used in this study. One group was vaccinated with a single dose of
      monovalent attenuated Bb vaccine and one group with a trivalent vaccine
      containing attenuated Bb, CPI, and CAV-2; dogs were vaccinated intranasally with
      a single dose of the respective vaccines. The third group served as unvaccinated
      controls. All vaccinated dogs subsequently developed serum antibody titers to Bb
      that persisted for at least 1 year. Following Bb challenge 1 year after
      vaccination, all vaccinated dogs, regardless of group, showed significantly fewer
      clinical signs and shed significantly fewer challenge organisms than unvaccinated
      controls. These results demonstrate that intranasal administration of a single
      dose of monovalent attenuated Bb vaccine or trivalent vaccine containing
      attenuated Bb, CPI, and CAV-2 provides 1 year of protection against Bb.

PMID- 19177331
TI  - Sensitivity of serum markers for pancreatitis in dogs with macroscopic evidence
      of pancreatitis.
AB  - Pancreatitis is recognized as an important and common problem in dogs, but
      diagnosis can be challenging. Recently, new assays for the measurement of trypsin
      a1-proteinase inhibitor complexes and canine pancreatic lipase immunoreactivity
      (cPLI and Spec cPL) have been developed and analytically validated. This is the
      first report of a direct comparison of the sensitivity of these and other more
      traditional serum markers for the diagnosis of canine pancreatitis in a subset of
      dogs with this disease (i.e., dogs with both macroscopic and microscopic changes
      characteristic of pancreatitis). Serum cPLI and Spec cPL concentrations showed
      the highest sensitivity for the diagnosis of pancreatitis in this group of
      patients. Further studies will be required to compare the specificity of these
      serum markers and thus determine their overall clinical utility.

PMID- 19177332
TI  - Comparison of florfenicol and tulathromycin for the treatment of undifferentiated
      fever in Alberta feedlot calves.
AB  - The purpose of this study was to compare the efficacy and cost-effectiveness of
      florfenicol versus tulathromycin for initial treatment of undifferentiated fever
      in fall-placed steer calves that received metaphylactic tilmicosin on arrival at
      the feedlot. No significant differences (P > .10) were observed in
      undifferentiated fever relapses or the crude case fatality rate. Calves treated
      with florfenicol had a lower case fatality rate (P = .04) for bovine respiratory
      disease and Histophilus disease than did calves treated with tulathromycin. The
      net economic advantage of florfenicol over tulathromycin (Can$17.70/treated
      animal) was based on differences in costs for the trial drug and calf replacement
      owing to bovine respiratory disease and Histophilus disease case fatality.

PMID- 19177333
TI  - Demonstration of passive protection in neonatal calves against colibacillosis
      following immunization of pregnant heifers at 3 months of gestation.
AB  - Enterotoxigenic Escherichia coli is one of the primary etiologic agents for
      diarrhea in neonatal calves. Immunization of dams can provide passive protection
      in neonatal calves; antibodies transferred through colostrum block colonization
      of bacteria, thereby preventing disease. In this study, healthy pregnant heifers
      were vaccinated at approximately 3 months of gestation with either a polyvalent
      oil-adjuvanted vaccine containing inactivated coronavirus, rotavirus, E. coli K99
      subunit antigen, and Clostridium perfringens b and e toxoid or normal saline as a
      placebo. Calves were allowed to nurse immediately after birth, were orally
      challenged with virulent heterologous enterotoxigenic E. coli at 1 day of age,
      and were observed for clinical signs of scours for 10 days. Signs of severe
      scours were noted in 75% of control calves and 28.6% of vaccinates, and the
      severity of scours was significantly higher (P = .0382) in the control group. The
      mortality rate was significantly higher (P = .0007) in the control group (80%)
      than in the vaccinate group (14%). These findings indicate that the vaccination
      of pregnant heifers at as early as 3 months of gestation (6 months before
      calving) provides passive protection in neonatal calves against colibacillosis.

PMID- 19177334
TI  - Comparative efficacy of tilmicosin versus tulathromycin as a metaphylactic
      antimicrobial in feedlot calves at moderate risk for respiratory disease.
AB  - The purpose of this study was to compare the efficacy and cost-effectiveness of
      tilmicosin (MIC) versus tulathromycin (DRAX) as a metaphylactic antimicrobial in
      feedlot calves at moderate risk for bovine respiratory disease (BRD). Calves that
      received DRAX had significantly (P < or = .05) lower initial BRD treatment rates
      compared with calves that received MIC. However, there were no significant
      differences in the BRD relapse rate, railer rate, total mortality rate, BRD
      mortality rate, average daily gain, and dry matter conversion between the two
      groups. The economic advantage of the MIC group was Can$8.29/animal. Based on
      these results, while DRAX was more efficacious in reducing initial treatments for
      BRD in feedlot calves at moderate risk for disease, MIC was more cost-effective.
      The lower initial BRD treatment costs in the DRAX group did not offset the higher
      metaphylactic cost of DRAX.

PMID- 19177335
TI  - Fetal abnormalities leading to third trimester abortion: nine-year experience
      from a single medical center.
AB  - OBJECTIVE: To assess fetal abnormalities and events leading to third-trimester
      abortion. METHODS: The study population included all parturient women with
      singleton pregnancy that underwent termination of pregnancy (TOP) in the third
      trimester in our institute because of fetal indications between 1998 and 2006.
      RESULTS: There were 777 cases of TOP due to fetal anomalies in our center during
      the study period, and 52 terminations were carried out in the third trimester.
      All cases of third-trimester abortions were due to severe malformations with high
      probability of perinatal death or severe handicap: 65.3% anomalies were
      structural, and 58.9% of them involved the central nervous system (CNS). Genetic
      indications included mostly genetic diseases, unlike aneupluidities in earlier
      terminations. Routine prenatal care raised suspicion of abnormalities in 22
      (42.3%) cases, and diagnosis was established by additional tests. Abnormal
      findings were either missed in 4 (7.7%) cases or developed later in 11 (21.1%)
      cases. No routine prenatal screening was performed in the remaining 15 (28.8%)
      cases. CONCLUSIONS: Third-trimester abortion may be obviated by timely screening
      and scanning in some cases. The possibility of late TOP should be considered in
      malformations occurring late in pregnancy and in cases that require meticulous
      evaluation and follow-up from earlier stages of gestation.

PMID- 19177336
TI  - Development of a piezo-actuated micro-teleoperation system for cell manipulation.
AB  - BACKGROUND: Intracytoplasmic sperm injection (ICSI) requires long training and
      has low success rates, primarily due to poor control over the injection force.
      Making force feedback available to the operator will improve the success rate of
      the injection task. A macro-micro-teleoperation system bridges the gap between
      the task performed at the micro-level and the macroscopic movements of the
      operator. The teleoperation slave manipulator should accurately position a needle
      to precisely penetrate a cell membrane. Piezoelectric actuators are widely used
      in micromanipulation applications; however, hysteresis non-linearity limits the
      accuracy of these actuators. METHOD: This paper presents a novel approach for
      utilizing a piezoelectric nano-stage as slave manipulator of a teleoperation
      system. The Prandtl-Ishlinskii (PI) model is used to model actuator hysteresis in
      a feedforward scheme to cancel out this non-linearity. To deal with the influence
      of parametric uncertainties, unmodelled dynamics and PI identification error, a
      perturbation term is added to the slave model and applies a sliding mode-based
      impedance control with perturbation estimation. RESULTS: The stability of entire
      system is guaranteed by Llewellyn's absolute stability criterion. The performance
      of the proposed controller was investigated through experiments for cell membrane
      penetration. CONCLUSION: The experimental results verified the accurate position
      tracking in free motion and simultaneous position and force tracking in contact
      with a low stiffness environment.

PMID- 19177337
TI  - Skeleton-based active catheter navigation.
AB  - BACKGROUND: The emergence of the active catheter has prompted the development of
      catheterization in minimally invasive surgery. However, it is still operated
      using only the physician's vision; information supplied by the guiding image and
      tracking sensors has not been fully utilized. METHODS: In order to supply the
      active catheter with more useful information for automatic navigation, we extract
      the skeleton of blood vessels by means of an improved distance transform method,
      and then present the crucial geometric information determining navigation. With
      the help of tracking sensors' position and pose information, two operations,
      advancement in the proximal end and direction selection in the distal end, are
      alternately implemented to insert the active catheter into a target blood vessel.
      RESULTS: The skeleton of the aortic arch reconstructed from slice images is
      extracted fast and automatically. A navigation path is generated on the skeleton
      by manually selecting the start and target points, and smoothed with the cubic
      cardinal spline curve. Crucial geometric information determining navigation is
      presented, as well as requirements for the catheter entering the target blood
      vessel. Using a shape memory alloy active catheter integrated with magnetic
      sensors, an experiment is carried out in a vascular model, in which the catheter
      is successfully inserted from the ascending aorta, via the aortic arch, into the
      brachiocephalic trunk. CONCLUSIONS: The navigation strategy proposed in this
      paper is feasible and has the advantage of increasing the automation of
      catheterization, enhancing the manoeuvrability of the active catheter and
      providing the guiding image with desirable interactivity.

PMID- 19177338
TI  - Family communication, genetic testing and colonoscopy screening in hereditary non
      polyposis colon cancer: a qualitative study.
AB  - OBJECTIVE: Genetic testing and colonoscopy is recommended for people with a
      strong history of colorectal cancer (CRC). However, families must communicate so
      that all members are aware of the risk. The study aimed to explore the factors
      influencing family communication about genetic risk and colonoscopy among people
      with a strong family history of CRC who attended a genetic clinic with a view to
      having a genetic test for hereditary non-polyposis colon cancer (HNPCC). METHODS:
      Interviews were held with 30 people with a high familial risk of colon cancer.
      The transcripts were transcribed verbatim and analysed using Interpretative
      Phenomenological Analysis. RESULTS: The family context, family history and
      perceptions about family duties and responsibilities were important motivators
      for communication about risk, genetic testing and colonoscopy and influenced
      participation in genetic testing and screening programmes. Participants reported
      usually communicating openly with their relatives about genetic risk and
      colonoscopy. Individuals felt a duty towards affected relatives and to their own
      children. The influence of the spouse and other relatives, particularly those
      affected by CRC, was also important. Colonoscopy was perceived to be
      embarrassing, unpleasant and sometimes painful. While there was sometimes anxiety
      about the result of the colonoscopy the results were usually reassuring.
      CONCLUSIONS: The family context and the experience of the family history can have
      an impact on communication, genetic testing and screening in HNPCC and this
      should be explored during counselling. Some individuals might benefit from
      support in communicating with relatives about genetic risk. Ways of improving the
      individual's experience of colonoscopy should also be examined.

PMID- 19177339
TI  - A generalized linear models approach to spatial scan statistics for covariate
      adjustment.
AB  - The spatial scan statistic proposed by Kulldorff (Commun. Statist.-Theory Methods
      1997; 26:1481-1496) is one of the most widely used methods for detecting spatial
      clusters and evaluating their statistical significance. However, it is not fully
      capable of adjusting for all types of confounding covariates. In this article, a
      generalized linear models (GLM) approach to construct spatial scan statistics,
      which is readily in a form for covariate adjustment, is proposed. Using GLM,
      spatial scan statistics for different probability models can be formulated in a
      single framework. The test statistic is based on the log-likelihood ratio test
      statistic and evaluated using Monte Carlo hypothesis testing. The proposed method
      is illustrated using Texas female breast cancer data concerning late versus early
      stage cancer cases with covariates of race/ethnicity and age group.

PMID- 19177341
TI  - Doctor, my breathing is better when I lie down.

PMID- 19177340
TI  - A recombinant fragment of human surfactant protein D lacking the short collagen
      like stalk fails to correct morphological alterations in lungs of SP-D deficient
      mice.
AB  - Emphysema-like pathology is a characteristic feature of surfactant protein D (SP
      D) knock-out mice. Treatment with a recombinant fragment of human SP-D consisting
      of a short collagen-like stalk (but not the entire collagen-like domain of native
      SP-D), neck, and carbohydrate recognizing domain (CRD) inhibits development of
      emphysema-like pathology in SP-D deficient mice. On the other hand, it has been
      shown that the entire collagen-like domain is necessary for preventing SP-D knock
      out mice from pulmonary emphysema development. Thus, in the present study, we
      aimed to elucidate the role of the short collagen-like stalk for the function of
      the recombinant fragment of human SP-D. We treated SP-D knock-out mice with a
      fragment of human SP-D lacking the short collagen-like stalk and compared the
      effects on lung morphology with results from untreated wild-type and SP-D knock
      out mice and from SP-D knock-out mice treated with a recombinant fragment of
      human SP-D including the short collagen-like stalk. The fragment of SP-D lacking
      the short collagen-like stalk failed to correct pulmonary emphysematous
      alterations demonstrating the importance of the short collagen-like stalk for the
      biological activity of the recombinant fragment of human SP-D.

PMID- 19177342
TI  - Reporting Down syndrome screening results: women's understanding of risk.
AB  - OBJECTIVES: To compare women's understanding of different methods of expressing
      Down syndrome risks. METHODS: A self-administered structured questionnaire given
      to 311 English-speaking women postpartum, at three maternity units. Understanding
      of numeric risk expression was assessed by women identifying whether a specified
      risk was higher, lower or the same as another nominated risk, expressed as two
      percentages, as two ratios or one of each. Perceptions of a high-risk result were
      obtained using display rankings of percentages and ratios. RESULTS: Response rate
      was 95% (294/311). Overall, women were poor comparing numeric risks whether
      expressed similarly (ratio vs. ratio or percentage vs. percentage) or not. When
      comparing similarly expressed risks, 66% (95% CI: 62-70%) of respondents were
      correct, considerably more than when asked to compare different risk expressions
      30% (95% CI: 26-34%), P < 0.0001. Women were more tolerant of risk when expressed
      as a percentage than as a ratio (median high risk for percentage form was 5%
      (1:20) and for ratio form was 1:200 (0.5%). CONCLUSIONS: Women's understanding of
      Down syndrome risk is dependent upon how risks are expressed. These findings may
      usefully direct how risk should be reported to women having prenatal screening
      for Down syndrome.

PMID- 19177345
TI  - Sorting the chaff from the wheat at the PDB.

PMID- 19177346
TI  - Crystal structures of the X-domains of a Group-1 and a Group-3 coronavirus reveal
      that ADP-ribose-binding may not be a conserved property.
AB  - The polyproteins of coronaviruses are cleaved by viral proteases into at least 15
      nonstructural proteins (Nsps). Consisting of five domains, Nsp3 is the largest of
      these (180-210 kDa). Among these domains, the so-called X-domain is believed to
      act as ADP-ribose-1''-phosphate phosphatase or to bind poly(ADP-ribose). However,
      here we show that the X-domain of Infectious Bronchitis Virus (strain Beaudette),
      a Group-3 coronavirus, fails to bind ADP-ribose. This is explained on the basis
      of the crystal structure of the protein, determined at two different pH values.
      For comparison, we also describe the crystal structure of the homologous X-domain
      from Human Coronavirus 229E, a Group-1 coronavirus, which does bind ADP-ribose.

PMID- 19177347
TI  - Monitoring anthrax toxin receptor dissociation from the protective antigen by
      NMR.
AB  - The binding of the Bacillus anthracis protective antigen (PA) to the host cell
      receptor is the first step toward the formation of the anthrax toxin, a
      tripartite set of proteins that include the enzymatic moieties edema factor (EF),
      and lethal factor (LF). PA is cleaved by a furin-like protease on the cell
      surface followed by the formation of a donut-shaped heptameric prepore. The
      prepore undergoes a major structural transition at acidic pH that results in the
      formation of a membrane spanning pore, an event which is dictated by interactions
      with the receptor and necessary for entry of EF and LF into the cell. We provide
      direct evidence using 1-dimensional (13)C-edited (1)H NMR that low pH induces
      dissociation of the Von-Willebrand factor A domain of the receptor capillary
      morphogenesis protein 2 (CMG2) from the prepore, but not the monomeric full
      length PA. Receptor dissociation is also observed using a carbon-13 labeled, 2
      fluorohistidine labeled CMG2, consistent with studies showing that protonation of
      His-121 in CMG2 is not a mechanism for receptor release. Dissociation is likely
      caused by the structural transition upon formation of a pore from the prepore
      state rather than protonation of residues at the receptor PA or prepore
      interface.

PMID- 19177348
TI  - Effect of trehalose on protein structure.
AB  - Trehalose is a ubiquitous molecule that occurs in lower and higher life forms but
      not in mammals. Till about 40 years ago, trehalose was visualized as a storage
      molecule, aiding the release of glucose for carrying out cellular functions. This
      perception has now changed dramatically. The role of trehalose has expanded, and
      this molecule has now been implicated in a variety of situations. Trehalose is
      synthesized as a stress-responsive factor when cells are exposed to environmental
      stresses like heat, cold, oxidation, desiccation, and so forth. When unicellular
      organisms are exposed to stress, they adapt by synthesizing huge amounts of
      trehalose, which helps them in retaining cellular integrity. This is thought to
      occur by prevention of denaturation of proteins by trehalose, which would
      otherwise degrade under stress. This explanation may be rational, since recently,
      trehalose has been shown to slow down the rate of polyglutamine-mediated protein
      aggregation and the resultant pathogenesis by stabilizing an aggregation-prone
      model protein. In recent years, trehalose has also proved useful in the
      cryopreservation of sperm and stem cells and in the development of a highly
      reliable organ preservation solution. This review aims to highlight the changing
      perception of the role of trehalose over the last 10 years and to propose common
      mechanisms that may be involved in all the myriad ways in which trehalose
      stabilizes protein structures. These will take into account the structure of
      trehalose molecule and its interactions with its environment, and the
      explanations will focus on the role of trehalose in preventing protein
      denaturation.

PMID- 19177349
TI  - Conformational changes within the HLA-A1:MAGE-A1 complex induced by binding of a
      recombinant antibody fragment with TCR-like specificity.
AB  - Although there is X-ray crystallographic evidence that the interaction between
      major histocompatibility complex (MHC, in humans HLA) class I molecules and T
      cell receptors (TCR) or killer cell Ig-like receptors (KIR) may be accompanied by
      considerable changes in the conformation of selected residues or even entire
      loops within TCR or KIR, conformational changes between receptor-bound and 
      unbound MHC class I molecules of comparable magnitude have not been observed so
      far. We have previously determined the structure of the MHC class I molecule HLA
      A1 bound to a melanoma antigen-encoding gene (MAGE)-A1-derived peptide in complex
      with a recombinant antibody fragment with TCR-like specificity, Fab-Hyb3. Here,
      we compare the X-ray structure of HLA-A1:MAGE-A1 with that complexed with Fab
      Hyb3 to gain insight into structural changes of the MHC molecule that might be
      induced by the interaction with the antibody fragment. Apart from the expulsion
      of several water molecules from the interface, Fab-Hyb3 binding results in major
      rearrangements (up to 5.5 A) of heavy chain residues Arg65, Gln72, Arg145, and
      Lys146. Residue 65 is frequently and residues 72 and 146 are occasionally
      involved in TCR binding-induced conformational changes, as revealed by a
      comparison with MHC class I structures in TCR-liganded and -unliganded forms. On
      the other hand, residue 145 is subject to a reorientation following engagement of
      HLA-Cw4 and KIR2DL1. Therefore, conformational changes within the HLA-A1:MAGE
      A1:Fab-Hyb3 complex include MHC residues that are also involved in reorientations
      in complexes with natural ligands, pointing to their central importance for the
      peptide-dependent recognition of MHC molecules.

PMID- 19177350
TI  - Structural features for the mechanism of antitumor action of a dimeric human
      pancreatic ribonuclease variant.
AB  - A specialized class of RNases shows a high cytotoxicity toward tumor cell lines,
      which is critically dependent on their ability to reach the cytosol and to evade
      the action of the ribonuclease inhibitor (RI). The cytotoxicity and antitumor
      activity of bovine seminal ribonuclease (BSRNase), which exists in the native
      state as an equilibrium mixture of a swapped and an unswapped dimer, are peculiar
      properties of the swapped form. A dimeric variant (HHP2-RNase) of human
      pancreatic RNase, in which the enzyme has been engineered to reproduce the
      sequence of BSRNase helix-II (Gln28-->Leu, Arg31-->Cys, Arg32-->Cys, and Asn34-
      >Lys) and to eliminate a negative charge on the surface (Glu111-->Gly), is also
      extremely cytotoxic. Surprisingly, this activity is associated also to the
      unswapped form of the protein. The crystal structure reveals that on this
      molecule the hinge regions, which are highly disordered in the unswapped form of
      BSRNase, adopt a very well-defined conformation in both subunits. The results
      suggest that the two hinge peptides and the two Leu28 side chains may provide an
      anchorage to a transient noncovalent dimer, which maintains Cys31 and Cys32 of
      the two subunits in proximity, thus stabilizing a quaternary structure, similar
      to that found for the noncovalent swapped dimer of BSRNase, that allows the
      molecule to escape RI and/or to enhance the formation of the interchain
      disulfides.

PMID- 19177351
TI  - Predicting repeat protein folding kinetics from an experimentally determined
      folding energy landscape.
AB  - The Notch ankyrin domain is a repeat protein whose folding has been characterized
      through equilibrium and kinetic measurements. In previous work, equilibrium
      folding free energies of truncated constructs were used to generate an
      experimentally determined folding energy landscape (Mello and Barrick, Proc Natl
      Acad Sci USA 2004;101:14102-14107). Here, this folding energy landscape is used
      to parameterize a kinetic model in which local transition probabilities between
      partly folded states are based on energy values from the landscape. The landscape
      based model correctly predicts highly diverse experimentally determined folding
      kinetics of the Notch ankyrin domain and sequence variants. These predictions
      include monophasic folding and biphasic unfolding, curvature in the unfolding
      limb of the chevron plot, population of a transient unfolding intermediate,
      relative folding rates of 19 variants spanning three orders of magnitude, and a
      change in the folding pathway that results from C-terminal stabilization. These
      findings indicate that the folding pathway(s) of the Notch ankyrin domain are
      thermodynamically selected: the primary determinants of kinetic behavior can be
      simply deduced from the local stability of individual repeats.

PMID- 19177352
TI  - Exploiting genomic patterns to discover new supramolecular protein assemblies.
AB  - Bacterial microcompartments are supramolecular protein assemblies that function
      as bacterial organelles by compartmentalizing particular enzymes and metabolic
      intermediates. The outer shells of these microcompartments are assembled from
      multiple paralogous structural proteins. Because the paralogs are required to
      assemble together, their genes are often transcribed together from the same
      operon, giving rise to a distinctive genomic pattern: multiple, typically small,
      paralogous proteins encoded in close proximity on the bacterial chromosome. To
      investigate the generality of this pattern in supramolecular assemblies, we
      employed a comparative genomics approach to search for protein families that show
      the same kind of genomic pattern as that exhibited by bacterial
      microcompartments. The results indicate that a variety of large supramolecular
      assemblies fit the pattern, including bacterial gas vesicles, bacterial pili, and
      small heat-shock protein complexes. The search also retrieved several widely
      distributed protein families of presently unknown function. The proteins from one
      of these families were characterized experimentally and found to show a behavior
      indicative of supramolecular assembly. We conclude that cotranscribed paralogs
      are a common feature of diverse supramolecular assemblies, and a useful genomic
      signature for discovering new kinds of large protein assemblies from genomic
      data.

PMID- 19177353
TI  - Solution structure of the RNA binding domain in the human muscleblind-like
      protein 2.
AB  - The muscleblind-like (MBNL) proteins 1, 2, and 3, which contain four CCCH zinc
      finger motifs (ZF1-4), are involved in the differentiation of muscle inclusion by
      controlling the splicing patterns of several pre-mRNAs. Especially, MBNL1 plays a
      crucial role in myotonic dystrophy. The CCCH zinc finger is a sequence motif
      found in many RNA binding proteins and is suggested to play an important role in
      the recognition of RNA molecules. Here, we solved the solution structures of both
      tandem zinc finger (TZF) motifs, TZF12 (comprising ZF1 and ZF2) and TZF34 (ZF3
      and ZF4), in MBNL2 from Homo sapiens. In TZF12 of MBNL2, ZF1 and ZF2 adopt a
      similar fold, as reported previously for the CCCH-type zinc fingers in the TIS11d
      protein. The linker between ZF1 and ZF2 in MBNL2 forms an antiparallel beta-sheet
      with the N-terminal extension of ZF1. Furthermore, ZF1 and ZF2 in MBNL2 interact
      with each other through hydrophobic interactions. Consequently, TZF12 forms a
      single, compact global fold, where ZF1 and ZF2 are approximately symmetrical
      about the C2 axis. The structure of the second tandem zinc finger (TZF34) in
      MBNL2 is similar to that of TZF12. This novel three-dimensional structure of the
      TZF domains in MBNL2 provides a basis for functional studies of the CCCH-type
      zinc finger motifs in the MBNL protein family.

PMID- 19177354
TI  - Crystal structure of checkpoint kinase 2 in complex with NSC 109555, a potent and
      selective inhibitor.
AB  - Checkpoint kinase 2 (Chk2), a ser/thr kinase involved in the ATM-Chk2 checkpoint
      pathway, is activated by genomic instability and DNA damage and results in either
      arrest of the cell cycle to allow DNA repair to occur or apoptosis if the DNA
      damage is severe. Drugs that specifically target Chk2 could be beneficial when
      administered in combination with current DNA-damaging agents used in cancer
      therapy. Recently, a novel inhibitor of Chk2, NSC 109555, was identified that
      exhibited high potency (IC(50) = 240 nM) and selectivity. This compound
      represents a new chemotype and lead for the development of novel Chk2 inhibitors
      that could be used as therapeutic agents for the treatment of cancer. To
      facilitate the discovery of new analogs of NSC 109555 with even greater potency
      and selectivity, we have solved the crystal structure of this inhibitor in
      complex with the catalytic domain of Chk2. The structure confirms that the
      compound is an ATP-competitive inhibitor, as the electron density clearly reveals
      that it occupies the ATP-binding pocket. However, the mode of inhibition differs
      from that of the previously studied structure of Chk2 in complex with
      debromohymenialdisine, a compound that inhibits both Chk1 and Chk2. A unique
      hydrophobic pocket in Chk2, located very close to the bound inhibitor, presents
      an opportunity for the rational design of compounds with higher binding affinity
      and greater selectivity.

PMID- 19177355
TI  - The oligomerization of OxyR in Escherichia coli.
AB  - We examine the contribution of residues at the dimer interface of the
      transcriptional regulator OxyR to oligomerization. Residues in contact across the
      dimer interface of OxyR were identified using the program Quaternary Contacts
      (QContacts). Site-directed mutagenesis was performed on the non-alanine or
      glycine residues identified in the resultant contact profile and the
      oligomerization ability of the mutant proteins was tested using the lambdacI
      repressor system to identify residues that are hot spots in OxyR. We compared the
      properties of these hot spots to those described in the literature from other
      systems. The hot spots identified in this study are not especially conserved
      amongst a set of OxyR orthologs.

PMID- 19177356
TI  - Insights from multiple structures of the shell proteins from the beta
      carboxysome.
AB  - Carboxysomes are primitive bacterial organelles that function as a part of a
      carbon concentrating mechanism (CCM) under conditions where inorganic carbon is
      limiting. The carboxysome enhances the efficiency of cellular carbon fixation by
      encapsulating together carbonic anhydrase and the CO(2)-fixing enzyme ribulose
      1,5-bisphosphate carboxylase/oxygenase (RuBisCO). The carboxysome has a roughly
      icosahedral shape with an outer shell between 800 and 1500 A in diameter, which
      is constructed from a few thousand small protein subunits. In the cyanobacterium
      Synechocystis sp. PCC 6803, the previous structure determination of two
      homologous shell protein subunits, CcmK2 and CcmK4, elucidated how the outer
      shell is formed by the tight packing of CcmK hexamers into a molecular layer.
      Here we describe the crystal structure of the hexameric shell protein CcmK1,
      along with structures of mutants of both CcmK1 and CcmK2 lacking their sometimes
      flexible C-terminal tails. Variations in the way hexamers pack into layers are
      noted, while sulfate ions bound in pores through the layer provide further
      support for the hypothesis that the pores serve for transport of substrates and
      products into and out of the carboxysome. One of the new structures provides a
      high-resolution (1.3 A) framework for subsequent computational studies of
      molecular transport through the pores. Crystal and solution studies of the C
      terminal deletion mutants demonstrate the tendency of the terminal segments to
      participate in protein--protein interactions, thereby providing a clue as to
      which side of the molecular layer of hexameric shell proteins is likely to face
      toward the carboxysome interior.

PMID- 19177357
TI  - A green fluorescent protein screen for identification of well-expressed membrane
      proteins from a cohort of extremophilic organisms.
AB  - Green fluorescent protein (GFP) fusion proteins provide a potentially facile tool
      for identification of well expressed, properly behaved membrane proteins for
      biochemical and structural study. Here, we present a GFP-expression survey of
      >300 membrane proteins from 18 bacterial and archaeal extremophiles, organisms
      expected to be rich sources of membrane proteins having robust biophysical
      properties. We find that GFP-fusion fluorescence intensity is an excellent
      indicator of over-expression potential. By employing a follow-up optimization
      protocol using a suite of non-GFP constructs and different expression
      temperatures, we obtain 0.5-15 mg L(-1) expression levels for 90% of the tested
      candidate proteins that pass the GFP screen. Evaluation of the results suggests
      that certain organisms may serve as better sources of well-expressed membrane
      proteins than others, that the degree to which codon usage matches the expression
      host is uncorrelated with success rate, and that the combination of GFP screening
      and expression optimization is essential for producing biochemically tractable
      quantities of material.

PMID- 19177359
TI  - High tolerance to simultaneous active-site mutations in TEM-1 beta-lactamase:
      Distinct mutational paths provide more generalized beta-lactam recognition.
AB  - The diversity in substrate recognition spectra exhibited by various beta
      lactamases can result from one or a few mutations in the active-site area. Using
      Escherichia coli TEM-1 beta-lactamase as a template that efficiently hydrolyses
      penicillins, we performed site-saturation mutagenesis simultaneously on two
      opposite faces of the active-site cavity. Residues 104 and 105 as well as 238,
      240, and 244 were targeted to verify their combinatorial effects on substrate
      specificity and enzyme activity and to probe for cooperativity between these
      residues. Selection for hydrolysis of an extended-spectrum cephalosporin,
      cefotaxime (CTX), led to the identification of a variety of novel mutational
      combinations. In vivo survival assays and in vitro characterization demonstrated
      a general tendency toward increased CTX and decreased penicillin resistance.
      Although selection was undertaken with CTX, productive binding (K(M)) was
      improved for all substrates tested, including benzylpenicillin for which
      catalytic turnover (k(cat)) was reduced. This indicates broadened substrate
      specificity, resulting in more generalized (or less specialized) variants. In
      most variants, the G238S mutation largely accounted for the observed properties,
      with additional mutations acting in an additive fashion to enhance these
      properties. However, the most efficient variant did not harbor the mutation G238S
      but combined two neighboring mutations that acted synergistically, also providing
      a catalytic generalization. Our exploration of concurrent mutations illustrates
      the high tolerance of the TEM-1 active site to multiple simultaneous mutations
      and reveals two distinct mutational paths to substrate spectrum diversification.

PMID- 19177358
TI  - Backbone structure of a small helical integral membrane protein: A unique
      structural characterization.
AB  - The structural characterization of small integral membrane proteins pose a
      significant challenge for structural biology because of the multitude of
      molecular interactions between the protein and its heterogeneous environment.
      Here, the three-dimensional backbone structure of Rv1761c from Mycobacterium
      tuberculosis has been characterized using solution NMR spectroscopy and
      dodecylphosphocholine (DPC) micelles as a membrane mimetic environment. This 127
      residue single transmembrane helix protein has a significant (10 kDa) C-terminal
      extramembranous domain. Five hundred and ninety distance, backbone dihedral, and
      orientational restraints were employed resulting in a 1.16 A rmsd backbone
      structure with a transmembrane domain defined at 0.40 A. The structure
      determination approach utilized residual dipolar coupling orientation data from
      partially aligned samples, long-range paramagnetic relaxation enhancement derived
      distances, and dihedral restraints from chemical shift indices to determine the
      global fold. This structural model of Rv1761c displays some influences by the
      membrane mimetic illustrating that the structure of these membrane proteins is
      dictated by a combination of the amino acid sequence and the protein's
      environment. These results demonstrate both the efficacy of the structural
      approach and the necessity to consider the biophysical properties of membrane
      mimetics when interpreting structural data of integral membrane proteins and, in
      particular, small integral membrane proteins.

PMID- 19177360
TI  - Single molecule effects of osteogenesis imperfecta mutations in tropocollagen
      protein domains.
AB  - Osteogenesis imperfecta (OI) is a genetic disease characterized by fragile bones,
      skeletal deformities and, in severe cases, prenatal death that affects more than
      1 in 10,000 individuals. Here we show by full atomistic simulation in explicit
      solvent that OI mutations have a significant influence on the mechanical
      properties of single tropocollagen molecules, and that the severity of different
      forms of OI is directly correlated with the reduction of the mechanical stiffness
      of individual tropocollagen molecules. The reduction of molecular stiffness
      provides insight into the molecular-scale mechanisms of the disease. The analysis
      of the molecular mechanisms reveals that physical parameters of side-chain volume
      and hydropathy index of the mutated residue control the loss of mechanical
      stiffness of individual tropocollagen molecules. We propose a model that enables
      us to predict the loss of stiffness based on these physical characteristics of
      mutations. This finding provides an atomistic-level mechanistic understanding of
      the role of OI mutations in defining the properties of the basic protein
      constituents, which could eventually lead to new strategies for diagnosis and
      treatment the disease. The focus on material properties and their role in genetic
      diseases is an important, yet so far only little explored, aspect in studying the
      mechanisms that lead to pathological conditions. The consideration of how
      material properties change in diseases could lead to a new paradigm that may
      expand beyond the focus on biochemical readings alone and include a
      characterization of material properties in diagnosis and treatment, an effort
      referred to as materiomics.

PMID- 19177361
TI  - Ion-specific modulation of protein interactions: anion-induced, reversible
      oligomerization of a fusion protein.
AB  - Ions can significantly modulate the solution interactions of proteins. We aim to
      demonstrate that the salt-dependent reversible heptamerization of a fusion
      protein called peptibody A or PbA is governed by anion-specific interactions with
      key arginyl and lysyl residues on its peptide arms. Peptibody A, an E. coli
      expressed, basic (pI = 8.8), homodimer (65.2 kDa), consisted of an IgG1-Fc with
      two, C-terminal peptide arms linked via penta-glycine linkers. Each peptide arm
      was composed of two, tandem, active sequences (SEYQGLPPQGWK) separated by a
      spacer (GSGSATGGSGGGASSGSGSATG). PbA was monomeric in 10 mM acetate, pH 5.0 but
      exhibited reversible self-association upon salt addition. The sedimentation
      coefficient (s(w)) and hydrodynamic diameter (D(H)) versus PbA concentration
      isotherms in the presence of 140 mM NaCl (A5N) displayed sharp increases in s(w)
      and D(H), reaching plateau values of 9 s and 16 nm by 10 mg/mL PbA. The D(H) and
      sedimentation equilibrium data in the plateau region (>12 mg/mL) indicated the
      oligomeric ensemble to be monodisperse (PdI = 0.05) with a z-average molecular
      weight (M(z)) of 433 kDa (stoichiometry = 7). There was no evidence of reversible
      self-association for an IgG1-Fc molecule in A5N by itself or in a mixture
      containing fluorescently labeled IgG1-Fc and PbA, indicative of PbA self-assembly
      being mediated through its peptide arms. Self-association increased with pH, NaCl
      concentration, and anion size (I(-) > Br(-) > Cl(-) > F(-)) but could be
      inhibited using soluble Trp-, Phe-, and Leu-amide salts (Trp > Phe > Leu). We
      propose that in the presence of salt (i) anion binding renders PbA self
      association competent by neutralizing the peptidyl arginyl and lysyl amines, (ii)
      self-association occurs via aromatic and hydrophobic interactions between the
      ..xxCTRWPWMC..xxxCTRWPWMCxx.. motifs, and (iii) at >10 mg/mL, PbA predominantly
      exists as heptameric clusters.

PMID- 19177362
TI  - OptGraft: A computational procedure for transferring a binding site onto an
      existing protein scaffold.
AB  - One of the many challenging tasks of protein design is the introduction of a
      completely new function into an existing protein scaffold. In this study, we
      introduce a new computational procedure OptGraft for placing a novel binding
      pocket onto a protein structure so as its geometry is minimally perturbed. This
      is accomplished by introducing a two-level procedure where we first identify
      where are the most appropriate locations to graft the new binding pocket into the
      protein fold by minimizing the departure from a set of geometric restraints using
      mixed-integer linear optimization. On identifying the suitable locations that can
      accommodate the new binding pocket, CHARMM energy calculations are employed to
      identify what mutations in the neighboring residues, if any, are needed to ensure
      that the minimum energy conformation of the binding pocket conserves the desired
      geometry. This computational framework is benchmarked against the results
      available in the literature for engineering a copper binding site into
      thioredoxin protein. Subsequently, OptGraft is used to guide the transfer of a
      calcium-binding pocket from thermitase protein (PDB: 1thm) into the first domain
      of CD2 protein (PDB:1hng). Experimental characterization of three de novo
      redesigned proteins with grafted calcium-binding centers demonstrated that they
      all exhibit high affinities for terbium (Kd) approximately 22, 38, and 55 microM)
      and can selectively bind calcium over magnesium.

PMID- 19177363
TI  - Thiol-disulfide organization in alliin lyase (alliinase) from garlic (Allium
      sativum).
AB  - Alliinase, an enzyme found in garlic, catalyzes the synthesis of the well-known
      chemically and therapeutically active compound allicin (diallyl thiosulfinate).
      The enzyme is a homodimeric glycoprotein that belongs to the fold-type I family
      of pyridoxal-5'-phosphate-dependent enzymes. There are 10 cysteine residues per
      alliinase monomer, eight of which form four disulfide bridges and two are free
      thiols. Cys368 and Cys376 form a S--S bridge located near the C-terminal and
      plays an important role in maintaining both the rigidity of the catalytic domain
      and the substrate-cofactor relative orientation. We demonstrated here that the
      chemical modification of allinase with the colored --SH reagent N-(4
      dimethylamino-3,5-dinitrophenyl) maleimide yielded chromophore-bearing peptides
      and showed that the Cys220 and Cys350 thiol groups are accesible in solution.
      Moreover, electron paramagnetic resonance kinetic measurements using disulfide
      containing a stable nitroxyl biradical showed that the accessibilities of the two
      --SH groups in Cys220 and Cys350 differ. Neither enzyme activity nor protein
      structure (measured by circular dichroism) were affected by the chemical
      modification of the free thiols, indicating that alliinase activity does not
      require free --SH groups. This allowed the oriented conjugation of alliinase, via
      the --SH groups, with low- or high-molecular-weight molecules as we showed here.
      Modification of the alliinase thiols with biotin and their subsequent binding to
      immobilized streptavidin enabled the efficient enzymatic production of allicin.

PMID- 19177364
TI  - High-resolution NMR characterization of a spider-silk mimetic composed of 15
      tandem repeats and a CRGD motif.
AB  - Multidimensional solution NMR spectroscopic techniques have been used to obtain
      atomic level information about a recombinant spider silk construct in hexafluoro
      isopropanol (HFIP). The synthetic 49 kDa silk-like protein mimics authentic silk
      from Nephila clavipes, with the inclusion of an extracellular matrix recognition
      motif. 2D (1)H-(15)N HSQC NMR spectroscopy reveals 33 cross peaks, which were
      assigned to amino acid residues in the semicrystalline repeat units. Signals from
      the amorphous segments in the primary sequence were weak and broad, suggesting
      that this region is highly dynamic and undergoing conformational exchange. An
      analysis of the deviations of the (13)C(alpha), (13)C(beta), and (13)CO chemical
      shifts relative to the expected random coil values reveals two highly alpha
      helical regions from amino acid 12-19 and 26-32, which comprise the polyalanine
      track and a GGLGSQ sequence. This finding is further supported by phi-value
      analysis and sequential and medium-range NOE interactions. Pulsed field gradient
      NMR measurements indicate that the topology of the silk mimetic in HFIP is
      nonglobular. Moreover, the 3D (15)N-NOESY HSQC spectrum exhibits few long-range
      NOEs. Similar spectral features have been observed for repeat modules in other
      polypeptides and are characteristic of an elongated conformation. The results
      provide a residue-specific description of a silk sequence in nonaqueous solution
      and may be insightful for understanding the fold and topology of highly
      concentrated, stable silk before spinning. Additionally, the insights obtained
      may find application in future design and large-scale production and storage of
      synthetic silks in organic solvents.

PMID- 19177365
TI  - Using affinity chromatography to engineer and characterize pH-dependent protein
      switches.
AB  - Conformational changes play important roles in the regulation of many enzymatic
      reactions. Specific motions of side chains, secondary structures, or entire
      protein domains facilitate the precise control of substrate selection, binding,
      and catalysis. Likewise, the engineering of allostery into proteins is envisioned
      to enable unprecedented control of chemical reactions and molecular assembly
      processes. We here study the structural effects of engineered ionizable residues
      in the core of the glutathione-S-transferase to convert this protein into a pH
      dependent allosteric protein. The underlying rational of these substitutions is
      that in the neutral state, an uncharged residue is compatible with the
      hydrophobic environment. In the charged state, however, the residue will invoke
      unfavorable interactions, which are likely to induce conformational changes that
      will affect the function of the enzyme. To test this hypothesis, we have
      engineered a single aspartate, cysteine, or histidine residue at a distance from
      the active site into the protein. All of the mutations exhibit a dramatic effect
      on the protein's affinity to bind glutathione. Whereas the aspartate or histidine
      mutations result in permanently nonbinding or binding versions of the protein,
      respectively, mutant GST50C exhibits distinct pH-dependent GSH-binding affinity.
      The crystal structures of the mutant protein GST50C under ionizing and
      nonionizing conditions reveal the recruitment of water molecules into the
      hydrophobic core to produce conformational changes that influence the protein's
      active site. The methodology described here to create and characterize engineered
      allosteric proteins through affinity chromatography may lead to a general
      approach to engineer effector-specific allostery into a protein structure.

PMID- 19177366
TI  - RosettaHoles: rapid assessment of protein core packing for structure prediction,
      refinement, design, and validation.
AB  - We present a novel method called RosettaHoles for visual and quantitative
      assessment of underpacking in the protein core. RosettaHoles generates a set of
      spherical cavity balls that fill the empty volume between atoms in the protein
      interior. For visualization, the cavity balls are aggregated into contiguous
      overlapping clusters and small cavities are discarded, leaving an uncluttered
      representation of the unfilled regions of space in a structure. For quantitative
      analysis, the cavity ball data are used to estimate the probability of observing
      a given cavity in a high-resolution crystal structure. RosettaHoles provides
      excellent discrimination between real and computationally generated structures,
      is predictive of incorrect regions in models, identifies problematic structures
      in the Protein Data Bank, and promises to be a useful validation tool for newly
      solved experimental structures.

PMID- 19177367
TI  - Structural modification of acyl carrier protein by butyryl group.
AB  - Fatty acid synthesis in bacteria is catalyzed by a set of individual enzymes
      known as the type II fatty acid synthase. Acyl carrier protein (ACP) shuttles the
      acyl intermediates between individual pathway enzymes. In this study, we
      determined the solution structures of three different forms of ACP, apo-ACP, ACP,
      and butyryl-ACP under identical experimental conditions. The structural studies
      revealed that attachment of butyryl acyl intermediate to ACP alters the
      conformation of ACP. This finding supports the more general notion that the
      attachment of different acyl intermediates alters the ACP structure to facilitate
      their recognition and turnover by the appropriate target enzymes.

PMID- 19177369
TI  - Mechanical unfolding of covalently linked GroES: evidence of structural subunit
      intermediates.
AB  - It is difficult to determine the structural stability of the individual subunits
      or protomers of many proteins in the cell that exist in an oligomeric or
      complexed state. In this study, we used single-molecule force spectroscopy on
      seven subunits of covalently linked cochaperonin GroES (ESC7) to evaluate the
      structural stability of the subunit. A modified form of ESC7 was immobilized on a
      mica surface. The force-extension profile obtained from the mechanical unfolding
      of this ESC7 showed a distinctive sawtooth pattern that is typical for
      multimodular proteins. When analyzed according to the worm-like chain model, the
      contour lengths calculated from the peaks in the profile suggested that linked
      GroES subunits unfold in distinct steps after the oligomeric ring structure of
      ESC7 is disrupted. The evidence that structured subunits of ESC7 withstand
      external force to some extent even after the perturbation of the oligomeric ring
      structure suggests that a stable monomeric intermediate is an important component
      of the equilibrium unfolding reaction of GroES.

PMID- 19177370
TI  - Anatomical Sciences Education: a new arrival in the medical education field.

PMID- 19177368
TI  - A summary of the measured pK values of the ionizable groups in folded proteins.
AB  - We tabulated 541 measured pK values reported in the literature for the Asp, Glu,
      His, Cys, Tyr, and Lys side chains, and the C and N termini of 78 folded
      proteins. The majority of these values are for the Asp, Glu, and His side chains.
      The average pK values are Asp 3.5 +/- 1.2 (139); Glu 4.2 +/- 0.9 (153); His 6.6
      +/- 1.0 (131); Cys 6.8 +/- 2.7 (25); Tyr 10.3 +/- 1.2 (20); Lys 10.5 +/- 1.1
      (35); C-terminus 3.3 +/- 0.8 (22) and N-terminus 7.7 +/- 0.5 (16). We compare
      these results with the measured pK values of these groups in alanine
      pentapeptides, and comment on our overall findings.

PMID- 19177371
TI  - Anatomical Sciences Education, clinical anatomy, and the anatomical record: take
      your pick.

PMID- 19177372
TI  - Modified use of team-based learning for effective delivery of medical gross
      anatomy and embryology.
AB  - Team-based learning (TBL) is an instructional strategy that combines independent
      out-of-class preparation for in-class discussion in small groups. This approach
      has been successfully adopted by a number of medical educators. This strategy
      allowed us to eliminate anatomy lectures and incorporate small-group active
      learning. Although our strategy is a modified use of classical TBL, in the text,
      we use the standard terminology of TBL for simplicity. We have modified classical
      TBL to fit our curricular needs and approach. Anatomy lectures were replaced with
      TBL activities that required pre-class reading of assigned materials, an
      individual self-assessment quiz, discussion of learning issues derived from the
      reading assignments, and then the group retaking the same quiz for discussion and
      deeper learning. Students' performances and their educational experiences in the
      TBL format were compared with the traditional lecture approach. We offer several
      in-house unit exams and a final comprehensive subject exam provided by the
      National Board of Medical Examiners. The students performed better in all exams
      following the TBL approach compared to traditional lecture-based teaching.
      Students acknowledged that TBL encouraged them to study regularly, allowed them
      to actively teach and learn from peers, and this served to improve their own exam
      performances. We found that a TBL approach in teaching anatomy allowed us to
      create an active learning environment that helped to improve students'
      performances. Based on our experience, other preclinical courses are now piloting
      TBL.

PMID- 19177373
TI  - CAVEman: Standardized anatomical context for biomedical data mapping.
AB  - The authors have created a software system called the CAVEman, for the visual
      integration and exploration of heterogeneous anatomical and biomedical data. The
      CAVEman can be applied for both education and research tasks. The main component
      of the system is a three-dimensional digital atlas of the adult male human
      anatomy, structured according to the nomenclature of Terminologia Anatomica. The
      underlying data-indexing mechanism uses standard ontologies to map a range of
      biomedical data types onto the atlas. The CAVEman system is now used to visualize
      genetic processes in the context of the human anatomy and to facilitate visual
      exploration of the data. Through the use of Javatrade mark software, the atlas
      based system is portable to virtually any computer environment, including
      personal computers and workstations. Existing Java tools for biomedical data
      analysis have been incorporated into the system. The affordability of virtual
      reality installations has increased dramatically over the last several years.
      This creates new opportunities for educational scenarios that model important
      processes in a patient's body, including gene expression patterns, metabolic
      activity, the effects of interventions such as drug treatments, and eventually
      surgical simulations.

PMID- 19177374
TI  - Evaluation of small-group teaching in human gross anatomy in a Caribbean medical
      school.
AB  - Although there are a number of medical schools in the Caribbean islands, very few
      reports have come out so far in the literature regarding the efficacy of small
      group teaching in them. The introduction of small-group teaching in the gross
      anatomy laboratory one and a half years ago at St. Matthew's University (SMU) on
      Grand Cayman appears to have had a significant positive impact on the academic
      achievement of students in anatomy. This study surveyed the responses of the
      students to the small-group learning method in gross anatomy at SMU using a
      structured questionnaire. The results show that our students prefer this small
      group learning method over a completely self-directed method in the gross anatomy
      lab because the study materials were carefully chosen and the study objectives
      were demonstrated by the resource person. However, teacher-centered teaching was
      deliberately avoided by fostering problem-solving skills in the anatomy lab
      sessions. Another aim of the small-group teaching at SMU was to develop the
      interpersonal and communication skills of the students, which are important in
      their later education and career.

PMID- 19177375
TI  - Tracheobronchial cast production and use in an undergraduate human anatomy
      course.
AB  - Silastic E RTV silicone was used to produce tracheobronchial cast for use in an
      undergraduate human anatomy course. Following air-drying, the trachea and lungs
      were injected with E RTV silicone and allowed to cure for 24 hr. The parenchyma
      was then removed from the tracheobronchial cast by maceration and boiling and
      then whitened in a 10% solution of hydrogen peroxide. The result was an
      anatomical replica that illustrates the branching pattern of the tracheobronchial
      tree and looks very similar to human even though canine lungs were used. In
      addition, this cast is very flexible and durable enough to stand up to repeated
      student handling.

PMID- 19177376
TI  - Coupled physical and digital cadaver dissection followed by a visual test
      protocol provides insights into the nature of anatomical knowledge and its
      evaluation.
AB  - This research effort compared and contrasted two conceptually different methods
      for the exploration of human anatomy in the first-year dissection laboratory by
      accomplished students: "physical" dissection using an embalmed cadaver and
      "digital" dissection using three-dimensional volume modeling of whole-body CT and
      MRI image sets acquired using the same cadaver. The goal was to understand the
      relative contributions each method makes toward student acquisition of intuitive
      sense of practical anatomical knowledge gained during "hands-on" structural
      exploration tasks. The main instruments for measuring anatomical knowledge under
      this conceptual model were questions generated using a classification system
      designed to assess both visual presentation manner and the corresponding response
      information required. Students were randomly divided into groups based on
      exploration method (physical or digital dissection) and then anatomical region.
      The physical dissectors proceeded with their direct methods, whereas the digital
      dissectors generated and manipulated indirect 3D digital models. After 6 weeks,
      corresponding student anatomical assignment teams compared their results using
      photography and animated digital visualizations. Finally, to see whether each
      method provided unique advantages, a visual test protocol of new visualizations
      based on the classification schema was administered. Results indicated that all
      students, regardless of gender, dissection method, and anatomical region
      dissected performed significantly better on questions presented as rotating
      models requiring spatial ordering or viewpoint determination responses in
      contrast to requests for specific lexical feature identifications. Additional
      results provided evidence of trends showing significant differences in gender and
      dissection method scores. These trends will be explored with further trials with
      larger populations.

PMID- 19177377
TI  - Designing patient-focused information: an opportunity for communicating
      anatomically related information.
AB  - Literature clearly demonstrates that there has been a large increase in the time
      devoted to teaching oral communication skills within medical curricula worldwide.
      In contrast, the ability to communicate with patients through written means does
      not appear to be a feature in many programmes, despite its fundamental importance
      in creating understanding of medicine within the general population. This article
      investigates one way patient-centered written communication has been integrated
      into part of the early training years of medical students using anatomically
      related material as a focus. Following a series of interactive seminars and
      debates as part of a student-selected component, students were asked to prepare a
      patient-focused information leaflet on a particular birth defect. The leaflets
      included aspects of anatomy and embryology as well as causes of the birth defect,
      signs and symptoms, treatments, outlook, and support mechanisms. Evaluation of
      the leaflets using set marking criteria and readability indexes showed that
      students had successfully targeted the chosen audiences. Feedback showed that the
      component was rated highly by the students in terms of quality, usefulness, and
      interest. Students viewed sessions as an excellent forum for appreciating the
      importance of and developing their own effective written communication skills. It
      is hoped that such developments will enhance the capacity of all potential
      doctors to communicate more effectively with patients and colleagues in both the
      written and spoken form.

PMID- 19177378
TI  - A minimally invasive approach to undergraduate anatomy teaching.
AB  - Anatomy is one of the cornerstones of medical education. Unfortunately,
      sufficient evidence has accumulated to suggest a worldwide decline in the
      resources and time allocated to its teaching. Integration of anatomy with
      clinical medicine has been frequently advocated as the solution to this academic
      crisis. Consequently, new ways of harnessing clinical relevance to the teaching
      of anatomy must be sought to make it applicable to contemporary clinical
      practice. Human cadavers have been used to teach laparoscopic skills to surgical
      trainees for some time. More recently, centers in the United States have piloted
      the use of minimally invasive techniques in the teaching of anatomy to
      undergraduates. We believe that the use of laparoscopy on human cadavers may also
      be used to complement the teaching of anatomy to United Kingdom and European
      medical students. This would not only familiarize students with the topography
      and morphology of human anatomy, but also with the concept of manipulating
      anatomical structures to achieve a clinical outcome. Other benefits include
      improved three-dimensional orientation, increased dexterity, and development team
      working skills amongst students. A UK feasibility study is currently underway.

PMID- 19177379
TI  - Letter to the editor.

PMID- 19177380
TI  - Driving effective communication through anatomy.

PMID- 19177381
TI  - Transforming clinical imaging data for virtual reality learning objects.
AB  - Advances in anatomical informatics, three-dimensional (3D) modeling, and virtual
      reality (VR) methods have made computer-based structural visualization a
      practical tool for education. In this article, the authors describe streamlined
      methods for producing VR "learning objects," standardized interactive software
      modules for anatomical sciences education, from newer high-resolution clinical
      imaging systems data. The key program is OsiriX, a free radiological image
      processing workstation software capable of directly reformatting and rendering
      volumetric 3D images. The transformed image arrays are then directly loaded into
      a commercial VR program to produce a variety of learning objects. Multiple types
      or "dimensions" of anatomical information can be embedded in these objects to
      provide different kinds of functions, including interactive atlases, examination
      questions, and complex, multistructure presentations. The use of clinical imaging
      data and workstation software speeds up the production of VR simulations,
      compared with reconstruction-based modeling from segmented cadaver cross
      sections, while providing useful examples of normal structural variation and
      pathological anatomy.

PMID- 19177382
TI  - An ethical solution to the challenges in teaching anatomy with dissection in the
      Chinese culture.
AB  - Universities and medical schools in China are faced with an ongoing shortage of
      cadavers for education and research because of insufficient numbers of cadaver
      donations. This article will examine the main obstacles to cadaver donation in
      the Chinese culture. These include superstitious traditional views about the
      body, a lack of legislation regulating donations, and a deficiency of effective
      channels for cadaver donations. Cadaver dissection has always been the most
      important method of teaching anatomy to medical students. Today, ethics courses
      have also become essential to a complete medical education. Contemporary
      physicians need to be equipped to navigate the myriad of moral and ethical issues
      inherent to modern medicine. In China, cadaver donations lag behind those in
      other countries, threatening to create valid disadvantages in medical education.
      New legislation and public education are necessary to remove cultural barriers
      and change Chinese views on cadaver donation. For this reason, the Department of
      Human Anatomy at Nanjing Medical University has established the "Educational
      Center for Medical Ethics." The goal of the Center is to promote proper respect
      for cadavers used for medical research and education, cherish the human lives the
      cadavers represent, and gain the trust of potential donors.

PMID- 19177383
TI  - Anatomists debate the value of a teaching credential.
AB  - Fewer and fewer programs are training graduate students and postdoctoral fellows
      in the classical anatomical disciplines. Nonetheless, there remains a need at all
      levels of clinical and basic science education for skilled instructors of
      anatomy, histology, and embryology. Two sessions at the 2006 annual meeting of
      the American Association of Anatomists (AAA) explored whether a system of
      accreditation would benefit students, institutions, and training programs.
      Although the value of accreditation was controversial, three challenges for the
      various anatomical societies emerged from these discussions: (1) To identify the
      skills and knowledge that should be shared among all anatomists, and the more
      specific skills and knowledge needed for the diverse settings in which anatomists
      work. (2) To address the historical inattention of institutions to the training
      of educators. (3) To develop strategies to lobby institutions and national
      organizations to support the training and work of educators in the anatomical
      sciences. One approach to meeting these challenges would be to develop guidelines
      for training programs. These guidelines would help graduate students seek the
      training they need, provide institutions with a benchmark to assess or develop
      training programs, and provide the basis for focusing lobbying efforts targeted
      at institutions or existing accreditation bodies.

PMID- 19177384
TI  - The influence of study methods and knowledge processing on academic success and
      long-term recall of anatomy learning by first-year veterinary students.
AB  - The purpose of this investigation was to quantitatively and qualitatively
      identify the study methods and learning strategies that veterinary students used
      to study anatomy during their first year of professional school and to correlate
      these with their academic achievement and long-term recall of information. It was
      surmised that active study methods would be more beneficial than passive method,
      but this hypothesis was not supported. The activity or passivity of each study
      method was secondary to the way in which the students processed the learning. No
      single study method was associated with academic success or long-term recall;
      instead, successful students used a multitude of study methods while the
      struggling students relied on a single method alone, although these methods
      varied from student to student. Students and their study methods were profiled
      using the qualitative technique known as phenomenographic analysis to find those
      who studied in a deep or surface way. The deep-processing students, who commonly
      used multiple study methods, not only succeeded in the class but also had better
      recall. Students who relied on a memorization-heavy surface approach to learning
      had limited recall and tended to perform poorly in the class. These results
      strongly suggest that by encouraging students to integrate their studying by
      using multiple methods educators can improve both student grades and recall of
      complex topics.

PMID- 19177385
TI  - Effects of instructional strategies using cross sections on the recognition of
      anatomical structures in correlated CT and MR images.
AB  - This research is an effort to best utilize the interactive anatomical images for
      instructional purposes based on cognitive load theory. Three studies explored the
      differential effects of three computer-based instructional strategies that use
      anatomical cross-sections to enhance the interpretation of radiological images.
      These strategies include: (1) cross-sectional images of the head that can be
      superimposed on radiological images, (2) transparent highlighting of anatomical
      structures in radiological images, and (3) cross-sectional images of the head
      with radiological images presented side-by-side. Data collected included: (1)
      time spent on instruction and on solving test questions, (2) mental effort during
      instruction and test, and (3) students' performance to identify anatomical
      structures in radiological images. Participants were 28 freshmen medical students
      (15 males and 13 females) and 208 biology students (190 females and 18 males).
      All studies used posttest-only control group design, and the collected data were
      analyzed by either t test or ANOVA. In self-directed computer-based environments,
      the strategies that used cross sections to improve students' ability to recognize
      anatomic structures in radiological images showed no significant positive
      effects. However, when increasing the complexity of the instructional materials,
      cross-sectional images imposed a higher cognitive load, as indicated by higher
      investment of mental effort. There is not enough evidence to claim that the
      simultaneous combination of cross sections and radiological images has no effect
      on the identification of anatomical structures in radiological images for
      novices. Further research that control for students' learning and cognitive style
      is needed to reach an informative conclusion.

PMID- 19177386
TI  - Professional storytelling in clinical dental anatomy teaching.
AB  - The aim of the present work was to see if storytelling in a clinical dental
      anatomy course would increase student satisfaction. We enhanced teaching by
      spontaneous storytelling in problem-based learning, in half of the third-year
      dentistry class. At the end of the course, we administered an anonymous
      questionnaire to the students in the class, consisting of 12 questions that
      students had to answer on a Likert scale of 1-5. An overall satisfaction score
      was obtained and we used a linear mixed model to compare differences in
      satisfaction between the two groups, with "group" as the fixed effect. We also
      conducted an exploratory factor analysis of the responses to investigate whether
      there were distinct constructs within the data. Overall satisfaction is high,
      with students "with stories" having higher satisfaction than those "without
      stories." The former group consistently gives higher satisfaction scores,
      regardless of which question is being asked. Factor analysis provides evidence
      that storytelling nurtures reflective learning, while students work on their
      clinical anatomy problems.

PMID- 19177387
TI  - Anatomy for biomedical engineers.
AB  - There is a perceived need for anatomy instruction for graduate students enrolled
      in a biomedical engineering program. This appeared especially important for
      students interested in and using medical images. These students typically did not
      have a strong background in biology. The authors arranged for students to dissect
      regions of the body that were of particular interest to them. Following
      completion of all the dissections, the students presented what they had learned
      to the entire class in the anatomy laboratory. This course has fulfilled an
      important need for our students.

PMID- 19177388
TI  - Traditional cadaveric anatomy...Gross! Endoscopic anatomy is where it is at.

PMID- 19177389
TI  - A new paradigm for teaching histology laboratories in Canada's first distributed
      medical school.
AB  - To address the critical problem of inadequate physician supply in rural British
      Columbia, The University of British Columbia (UBC) launched an innovative,
      expanded and distributed medical program in 2004-2005. Medical students engage in
      a common curriculum at three geographically distinct sites across B.C.: in
      Vancouver, Prince George and Victoria. The distribution of the core Histology
      course required a thorough revision of our instructional methodology. We here
      report our progress and address the question "How does one successfully
      distribute Histology teaching to remote sites while maintaining the highest of
      educational standards?" The experience at UBC points to three specific challenges
      in developing a distributed Histology curriculum: (i) ensuring equitable student
      access to high quality histological images, (ii) designing and implementing a
      reliable, state-of-the-art technological infrastructure that allows for real-time
      teaching and interactivity across geographically separate sites and (iii)
      ensuring continued student access to faculty content expertise. High quality
      images--available through any internet connection--are provided within a new
      virtual slide box library of 300 light microscopic and 190 electron microscopic
      images. Our technological needs are met through a robust and reliable
      videoconference system that allows for live, simultaneous communication of
      audio/visual materials across the three sites. This system also ensures student
      access to faculty content expertise during all didactic teaching sessions.
      Student examination results and surveys demonstrate that the distribution of our
      Histology curriculum has been successful.

PMID- 19177390
TI  - Development of a synergistic case-based microanatomy curriculum.
AB  - This paper discusses the development of an interactive approach to teaching and
      assessing a microanatomy curriculum in an innovative medical school program. As
      an alternative to lectures and labs, students are engaged in interactive seminars
      focused on discussion of clinical and research-based cases matched with normal
      histology and pathology slides. A virtual microscopic system is used rather than
      the traditional glass slide and light microscope. Evaluation of student
      performance consists of self-assessment board style questions, concept appraisal
      problems, and utilization of a portfolio system where the assessment pieces are
      continuously integrated as part of written formative and summative assessments.

PMID- 19177391
TI  - An explorative learning approach to teaching clinical anatomy using student
      generated content.
AB  - Translating basic sciences into a clinical framework has been approached through
      the implementation of various teaching techniques aimed at using a patient case
      scenario to facilitate learning. These techniques present students with a
      specific patient case and lead the students to discuss physiological processes
      through analysis of provided data supported by independent learning and research.
      However, no literature exists that describes a reverse teaching methodology in
      which students are given disease diagnosis and then asked to construct a patient
      case. This article discusses an explorative learning approach introduced in the
      gross anatomy course in which students were asked to use clinical skills and
      reasoning to create a patient case. The online knowledge-sharing portal utilizing
      MediaWiki provided a necessary base for students in completing their task. Teams
      were given 4 weeks to complete their written online project with weekly feedback
      provided by 3rd year teaching assistants using the Wiki discussion page. A survey
      was performed to assess competence regarding a patient write up and oral
      presentation. Skills that the teams acquired through the completion of this
      project will benefit future patient interactions. This project also emphasized
      and reinforced the importance of effective communication, leadership, and
      teamwork. This study shows that a clinical anatomy project that incorporates
      explorative learning can be an effective way of introducing students to the
      skills needed for patient write ups and oral presentations. Furthermore this
      approach to learning allows students to excel during their clinical years and to
      correlate anatomy to clinical diagnoses.

PMID- 19177392
TI  - Anatomy: spotlight on Africa.
AB  - Anatomy departments across Africa were surveyed regarding the type of curriculum
      and method of delivery of their medical courses. While the response rate was low,
      African anatomy departments appear to be in line with the rest of the world in
      that many have introduced problem based learning, have hours that are within the
      range of western medical schools and appear to be well resourced. Human body
      dissection is a constant and strong aspect of the majority of the courses
      surveyed. The staff to student ratio appears to be relatively high in Africa, but
      in many of the responding African institutions, there appears to be little
      difficulty in attracting suitable faculty (including those who are medically
      qualified) to teach anatomy. Retaining this faculty, in some cases, may be
      difficult because of a global demand for anatomy educators.

PMID- 19177393
TI  - Functional anatomy of the cardiovascular system: professional development for
      PreK-3 teachers using a "train and equip" method results in learning
      opportunities for students.
AB  - Preadolescent students are interested in learning the structure and function of
      the human body. However, their teachers are not trained in this content. The
      purpose of this project was to expand a successful outreach effort in the health
      sciences for grade 7-12 teachers to include PreK-3 teachers. A "Healthy Hearts"
      workshop was offered to train the teachers in relevant content and also to give
      them a resource kit of supplies and equipment to facilitate the transference of
      the training into educational opportunities for their students. The workshop
      included many role-playing activities and use of all items in the resource kit. A
      total of 25 workshops were conducted in 14 different community locations with 716
      PreK-3 teachers attending from 169 communities representing 59 (79%) of the
      state's 75 counties. African American (AA) teacher participation was 35%, twice
      the state AA population rate and 3.5x the AA public school teacher rate. Pre to
      Posttest scores increased an average of 15%. The results of the evaluation
      measures regarding the workshop and the transference of the training and use of
      resource kit items into learning opportunities for students were excellent.
      Universities have the capability, perhaps the responsibility, to provide the much
      needed professional development training to PreK-12 teachers. Anatomists in
      medical and nonmedical school settings are well positioned to participate in this
      process and help close the gap between the interest young children have in
      learning about the human body and the lack of teacher training in this content.

PMID- 19177394
TI  - A simplified approach to teaching medical students ocular movements and the
      rationale in testing the oculomotor, trochlear, and abducent nerves.
AB  - The actions of the individual extraocular muscles are best explained to medical
      students in a lecture format by showing the relationship of each muscle to the
      axes of the globe and the walls of the bony orbit. The lateral and medial rectus
      muscles cross only the vertical axis, and consequently, cause only abduction and
      adduction, respectively. These muscles can be tested simply by asking the patient
      to abduct or adduct. Inability to do so indicates that the muscles and/or their
      innervation have been compromised. In contrast, the superior and inferior oblique
      and rectus muscles cross all three axes (vertical, horizontal, and
      anteroposterior) of the globe. Therefore, concentric contraction of each of these
      muscles results in three movements; abduction or adduction, elevation or
      depression, and intorsion or extorsion. These muscles must be tested with a
      sequence of two movements. Gaze can be either elevated or depressed by both an
      oblique and a rectus muscle. If abduction or adduction occurs first, one muscle
      of the pair becomes incapable of causing elevation or depression of the pupil.
      The rationale for abducting or adducting first is that either the oblique or
      rectus muscle of the pair will no longer cross the horizontal axis and will then
      be unable to effect the desired movement. Inability to elevate or depress gaze
      from the abducted or adducted position shows which muscle, the oblique or rectus,
      and/or its innervation has been compromised.

PMID- 19177395
TI  - The anatomy of self-defense.
AB  - The following study describes a creative application of anatomical principles in
      the instruction of self-defense. Undergraduates at the University of Kentucky
      were invited to a special lecture that featured a series of self-defense moves
      introduced by a local police officer. Following a demonstration of each self
      defense tactic, the students were briefed on the anatomy of both the victim and
      the assailant that contributed to the overall effectiveness of each move. This
      approach was unique in that students learned critical knowledge of self-defense
      while reinforcing anatomical principles previously introduced in class. Moreover,
      this integration of topics prompted students to think about their response to
      potentially dangerous situations on campus.

PMID- 19177396
TI  - Perceptions of anatomy education--a student's view.
AB  - Changes in anatomy education over the last two decades have, in large part, led
      to less emphasis on gross anatomy in the medical curriculum. This has led many to
      question whether streamlined anatomy courses truly provide adequate preparation
      for medical practice. Rather than wondering about the effects of these changes,
      we should be actively seeking answers and promoting understanding between
      professors, clinicians, and students about what anatomy education is and what it
      should be.

PMID- 19177397
TI  - Laparoscopic anatomy for medical students.

PMID- 19177399
TI  - Shaped like a Greek letter.

PMID- 19177400
TI  - Body painting as a tool in clinical anatomy teaching.
AB  - The teaching of human anatomy has had to respond to significant changes in
      medical curricula, and it behooves anatomists to devise alternative strategies to
      effectively facilitate learning of the discipline by medical students in an
      integrated, applied, relevant, and contextual framework. In many medical schools,
      the lack of cadaver dissection as the primary method of learning is driving
      changes to more varied and novel learning and teaching methodologies. The present
      article describes the introduction and evaluation of a range of body painting
      exercises in a medical curriculum. Body painting was introduced into integrated
      clinical skills teaching sessions which included clinically important aspects of
      respiratory system, musculoskeletal system, and topics in regional anatomy
      including head and neck. Nontoxic body paints, easels, a mixture of brush sizes,
      and anatomical images were supplied. Students were allowed between 20 and 40 min
      to complete body painting tasks, in which they were encouraged to alternate
      between painting and acting as a model. Students were encouraged to use life-like
      rendering and coloration where appropriate. Evaluation of these sessions was
      performed at the end of the semester as part of a larger evaluation process. The
      kinesthetic nature and active participation together with the powerful visual
      images of underlying anatomy appear to contribute to the value of body painting
      as a teaching exercise. In addition, it may have the added bonus of helping break
      down apprehension regarding peer-peer examination. Some practical advice on
      introducing this method of teaching in medical curricula based on the outcomes of
      the evaluation is given. On the basis of our experience and student feedback, we
      strongly advocate the use of body painting as an adjunct to surface anatomy and
      clinical skills teaching classes.

PMID- 19177401
TI  - Self-directed learning in gross human anatomy: assessment outcomes and student
      perceptions.
AB  - Speech pathology students enrolled in a lecture-based gross human anatomy program
      completed two out of nine topics in self-directed mode. Student performance in
      quizzes was compared for the two modes, and the students completed questionnaires
      on their perceptions of the self-directed mode of delivery. Students performed as
      well in the first self-directed topic as they did in lecture-based material, but
      performance declined significantly on the second self-directed topic.
      Correlations showed that students who performed well in lecture-based topics also
      performed well on self-directed topics. The major issues that arose in the
      student questionnaires were primarily related to the amount of content in the
      topics and the length of time required for completion. We conclude that there is
      a strong need for appropriate design of distance education materials to reflect
      student perceptions of length, content, and time investment, and more importantly
      that there is a need to ensure extensive communication and support of students
      studying in distance education/self-directed modes for the first time.

PMID- 19177402
TI  - Learning to be a doctor while learning anatomy!
AB  - This article presents results from a longitudinal study following a cohort of
      medical students. Semistructured interviews are conducted every year, in which
      the students tell about their experiences learning medicine, their daily life,
      and their social activities in relation to university. The aim of the study is to
      analyze how medical students develop their professional competencies, values, and
      attitudes. This article focuses on the medical student's professional development
      in relation to the process of studying and learning anatomy. We analyze
      interviews conducted while the students are in their third and fifth semester.
      Anatomy plays a significant role in the medical student's educational process, on
      both a cognitive and emotional level. It seems that students in learning the
      subject matter adapt to fundamental values in the medical profession and are thus
      transformed into real medical students, sharing a unique experience. The
      implications for curricular development and professionalism are discussed, and
      this article argues that the issue of professionalism must be addressed in the
      educational process in the preclinical years and in relation to the basic
      sciences.

PMID- 19177403
TI  - Effect of the use of instructional anatomy videos on student performance.
AB  - Medical schools have reduced the time allotted to anatomy instruction.
      Consequently, schools engage students in more independent settings using
      information and communication technologies (ICT). There has been limited research
      in the use of video aids, a type of ICT, to enhance anatomy examination
      performance. The objective of this study is to describe the design, usage, and
      effect on examination performance of eight locally developed instructional
      anatomy videos. First-year UCSF medical students (n = 141) had access to the
      videos. They reported their video usage, reason for usage, and satisfaction. The
      prior year students (n = 141) served as a historical control group. Anatomy and
      radiology examination performance was compared between groups while controlling
      for prior performance. The students with and without access to the videos did not
      differ in examination performance. Sixty-one (43%) students in the experimental
      group responded to the survey. Of these, 79% reported using at least one video,
      viewing an average of 4.75 of the eight videos. They watched 3.27 (SD = 1.57,
      range 1-5) of the five anatomy videos and 1.48 (SD = 1.35; range 0-3) of the
      three radiology videos. In a regression analysis controlling for age and MCAT
      scores, using the anatomy videos at least once improved anatomy examination
      performance by 3.4% (P-value = 0.007). There was no relationship between
      radiology video usage and radiology exam score. Video resource availability did
      not enhance student performance in anatomy and radiology. However, when analyzing
      performance for those whom we knew level of video use, there was a statistically
      different and higher anatomy achievement.

PMID- 19177404
TI  - Thinking outside the (voice) box: a case study of students' perceptions of the
      relevance of anatomy to speech pathology.
AB  - Speech pathology students readily identify the importance of a sound
      understanding of anatomical structures central to their intended profession. In
      contrast, they often do not recognize the relevance of a broader understanding of
      structure and function. This study aimed to explore students' perceptions of the
      relevance of anatomy to speech pathology. The effect of two learning activities
      on students' perceptions was also evaluated. First, a written assignment required
      students to illustrate the relevance of anatomy to speech pathology by using an
      example selected from one of the four alternative structures. The second approach
      was the introduction of brief "scenarios" with directed questions into the
      practical class. The effects of these activities were assessed via two surveys
      designed to evaluate students' perceptions of the relevance of anatomy before and
      during the course experience. A focus group was conducted to clarify and extend
      discussion of issues arising from the survey data. The results showed that the
      students perceived some course material as irrelevant to speech pathology. The
      importance of relevance to the students' "state" motivation was well supported by
      the data. Although the students believed that the learning activities helped
      their understanding of the relevance of anatomy, some structures were considered
      less relevant at the end of the course. It is likely that the perceived amount of
      content and surface approach to learning may have prevented students from
      "thinking outside the box" regarding which anatomical structures are relevant to
      the profession.

PMID- 19177405
TI  - A usability study of users' perceptions toward a multimedia computer-assisted
      learning tool for neuroanatomy.
AB  - This usability study evaluated users' perceptions of a multimedia prototype for a
      new e-learning tool: Anatomy of the Central Nervous System: A Multimedia Course.
      Usability testing is a collection of formative evaluation methods that inform the
      developmental design of e-learning tools to maximize user acceptance,
      satisfaction, and adoption. Sixty-two study participants piloted the prototype
      and completed a usability questionnaire designed to measure two usability
      properties: program need and program applicability. Statistical analyses were
      used to test the hypothesis that the multimedia prototype was well designed and
      highly usable, it was perceived as: (1) highly needed across a spectrum of
      educational contexts, (2) highly applicable in supporting the pedagogical
      processes of teaching and learning neuroanatomy, and (3) was highly usable by all
      types of users. Three independent variables represented user differences: level
      of expertise (faculty vs. student), age, and gender. Analysis of the results
      supports the research hypotheses that the prototype was designed well for
      different types of users in various educational contexts and for supporting the
      pedagogy of neuroanatomy. In addition, the results suggest that the multimedia
      program will be most useful as a neuroanatomy review tool for health-professions
      students preparing for licensing or board exams. This study demonstrates the
      importance of integrating quality properties of usability with principles of
      human learning during the instructional design process for multimedia products.

PMID- 19177406
TI  - How much anatomy is enough?
AB  - Innovations in undergraduate medical education, such as integration of
      disciplines and problem based learning, have given rise to concerns about
      students' knowledge of anatomy. This article originated from several studies
      investigating the knowledge of anatomy of students at the eight Dutch medical
      schools. The studies showed that undergraduate students uniformly perceived
      deficiencies in their anatomical knowledge when they started clinical training
      regardless of their school's didactic approach. A study assessing students'
      actual knowledge of clinical anatomy revealed no relationship between students'
      knowledge and the school's didactic approach. Test failure rates based on
      absolute standards set by different groups of experts were indicative of
      unsatisfactory levels of anatomical knowledge, although standards differed
      markedly between the groups of experts. Good test performance by students seems
      to be related to total teaching time for anatomy, teaching in clinical context,
      and revisiting anatomy topics in the course of the curriculum. These factors
      appeared to outweigh the effects of disciplinary integration or whether the
      curriculum was problem-based or traditional.

PMID- 19177407
TI  - Problem-based learning benefits for basic sciences education.

PMID- 19177408
TI  - Restocking the pond.

PMID- 19177409
TI  - Congratulations to Geoff Norman.

PMID- 19177410
TI  - Situational leadership applied to the dissertation process.
AB  - For more than 40 years, concern has been expressed over the attrition rate of
      students in Ph.D. programs in American universities. Although there are a number
      of significant factors at work, attrition of doctoral students in sciences such
      as anatomy may lead to a dearth of trained teaching anatomists as well as
      research scientists in the anatomical sciences. Failure to complete the Ph.D.
      process including the dissertation carries a high cost, not only to the students
      who fail to complete their programs, but also to society at large due to the
      expenditure of scarce education resources. A variety of factors have been
      examined in the various studies, but two stands out of major interest for this
      article: student personality factors such as perseverance and the level of
      faculty mentoring/support to the students during the graduate education process.
      A new approach to providing faculty support based on the needs of the individual
      student is presented in this article. Situational Leadership(R) has been
      developed over the past 40 years by Paul Hersey and Kenneth Blanchard and their
      associates. This leadership model is unique in that when it is applied to the
      dissertation process, it requires the faculty member to determine the readiness
      level of the graduate student. Because each student is a unique individual, the
      faculty mentor assesses each student based on the specific task at hand in order
      to provide the appropriate style of mentorship each student requires.

PMID- 19177411
TI  - Peer teaching among physical therapy students during human gross anatomy:
      perceptions of peer teachers and students.
AB  - Despite nearly 200 accredited entry-level physical therapist education programs
      in the United States that culminate in a doctoral degree, only a paucity of
      reports have been published regarding the efficacy of peer teaching in gross
      anatomy. No one has described the usefulness of peer teaching from the viewpoint
      of the peer teacher. An organized peer teaching method provided by four second
      year doctors of physical therapy (DPT) students in a semester course in gross
      anatomy had a positive impact on the academic performance in gross anatomy of
      first-year DPT students. The unique feature of the weekly peer teaching sessions
      was a packet assembled by the second-year peer teachers, which contained
      diagrams, fill-in-the blank questions, and helpful mnemonic devices. This study
      surveyed perceptions of first-year DPT students in response to a peer teaching
      method, using a structured 10-item questionnaire and a five-point Likert scale.
      Second-year DPT peer teachers provided written reflections about the benefits and
      challenges of serving as a peer teacher. Results revealed that 13 planned peer
      teaching experiences provided by four second-year DPT students were valuable and
      promoted a firm understanding of anatomical relationships important for the
      clinical competence of physical therapist students. Moreover, peer teachers
      acknowledged acquiring clinically desirable teaching, academic, organizational,
      and time management skills from the experience. As a result, physical therapist
      educators may wish to consider this model of peer teaching to augment their
      teaching strategies for a class in gross human anatomy.

PMID- 19177412
TI  - Dilated canine hearts: a specimen for teaching cardiac anatomy.
AB  - Dilated canine hearts were used to teach undergraduate students internal and
      external cardiac anatomy. The specimens were dilated using hydrostatic pressure
      and then fixed using 5% formalin. These specimens provided the students with an
      alternative to prepackaged embalmed hearts and anatomical models for studying the
      external and internal cardiac anatomy. In addition, the dilated hearts are more
      similar to the organ they encounter within the thoracic cavity of their dissected
      animal. This gives the students a better chance of developing a three-dimensional
      understanding of the heart.

PMID- 19177413
TI  - Student attitudes to whole body donation are influenced by dissection.
AB  - Given the important role that anatomical dissection plays in the shaping of
      medical student attitudes to life and death, these attitudes have not been
      evaluated in the context of whole body donation for medical science. First year
      students of anatomy in an Irish university medical school were surveyed by
      questionnaire before and after the initial dissection and again after 9 weeks of
      anatomical dissection. Analysis of student responses to the idea of whole body
      donation by an unrelated stranger, a family member, or by the respondent showed
      that a priori attitudes to donation by a stranger did not change with exposure to
      dissection. However, student opposition to donation by a family member was
      evident immediately after the initial dissection and was sustained throughout the
      duration of this study. Support for the idea of donating their bodies to medical
      science decreased significantly among respondents after exposure to dissection
      (31.5% before dissection, 19.6% after dissecting for 9 weeks) but not to levels
      reported in the general population in other studies. This study demonstrates that
      where dissection forms a part of anatomy teaching, students expect to learn
      anatomy by dissecting donors whom they do not know. As a potential donor
      population, students are reluctant to become emotionally involved in the donation
      process and are unwilling to become donors themselves.

PMID- 19177414
TI  - Giving ourselves: the ethics of anatomical donation.
AB  - In some European countries, such as Italy, medical education is threatened by a
      dearth of anatomical specimens. Such a shortage could spread to other nations,
      including the United States. This article addresses two ethical questions in body
      donation. Why might people choose to donate their bodies to education and
      science? What sorts of ethical appeals might anatomists, physicians, and other
      health professionals make to patients and family members for anatomical donation?
      Two models of giving, egoistic and liberal, merit close examination.

PMID- 19177415
TI  - Computerized grading of anatomy laboratory practical examinations.
AB  - At the Medical College of Wisconsin, a procedure was developed to allow
      computerized grading and grade reporting of laboratory practical examinations in
      the Clinical Human Anatomy course. At the start of the course, first year medical
      students were given four Lists of Structures. On these lists, numbered items were
      arranged alphabetically; the items were anatomical structures that could be
      tagged on a given lab practical examination. Each lab exam featured an anatomy
      laboratory component and a computer laboratory component. For the anatomy lab
      component, students moved from one question station to another at timed intervals
      and identified tagged anatomical structures. As students identified a tagged
      structure, they referred to a copy of the list (provided with their answer sheet)
      and wrote the number corresponding to the structure on their answer sheet.
      Immediately after the anatomy lab component, students were escorted to a computer
      instruction laboratory where they typed their answer numbers into a secured
      testing component of a learning management system that recorded their answers for
      automatic grading. After a brief review of examination scores and item analysis
      by faculty, exam scores were reported to students electronically. Adding this
      brief computer component to each lab exam greatly reduced faculty grading time,
      reduced grading errors and provided faster performance feedback for students
      without changing overall student performance.

PMID- 19177416
TI  - Performance in a prematriculation gross anatomy course as a predictor of
      performance in medical school.
AB  - The University of California at Davis School of Medicine offers a
      prematriculation program to nontraditional students. As part of the program,
      students take a 7-day course on the gross anatomy of the upper limb that
      concludes with a written examination and a practical examination based on
      prosections. Here, the performance of students who took the course from 2002 to
      2004 (n = 48) is compared with their performance in the medical gross anatomy
      course as well as their performance on Step 1 of the United States Medical
      Licensing Examination (USMLE). Both rank in the prematriculation program's
      anatomy course and the score on the examination were correlated (significant at
      the 0.01 level) with performance on the medical gross anatomy midterm and final
      examinations, the overall final grade, and class rank. Performance in the
      prematriculation anatomy course was also correlated with the score on Step 1 of
      the USMLE (rank significant at the 0.02 level; examination score, significant at
      the 0.05 level). Students who took the prematriculation course who eventually
      withdrew, were dismissed for academic reasons, or who failed the first attempt at
      the Step 1 of the licensing exam (n = 5) had a significantly lower score (77.6 +/
      11.1; P < 0.05) on the prematriculation examination than did successful
      prematriculation students (86.2 +/- 7.9). Thus, a gross anatomy examination
      following a short prematriculation course can be a predictor not only of medical
      student performance in anatomy, but also of performance on a standardized
      licensing examination.

PMID- 19177417
TI  - Anatomy: spotlight on Africa revisited.

PMID- 19177418
TI  - Spotlight on teaching of anatomy in Ethiopia.

PMID- 19177421
TI  - Inverse-electron-demand Diels-Alder reaction as a highly efficient chemoselective
      ligation procedure: synthesis and function of a BioShuttle for temozolomide
      transport into prostate cancer cells.
AB  - Hormone-refractory prostate cancer (HRPC), insensitive to most cytostatic
      interventions, features low response rates and bad prognosis. Studies with HRPC
      treated with temozolomide (TMZ) showed a poor response and the results were
      discouraging. Therefore, TMZ has been considered to be ineffective for the
      treatment of patients with symptomatic and progressive HRPC. A solution to this
      problem is demonstrated in this study by combining proper solid-phase peptide
      synthesis and a chemoselective new 'click' chemistry based on the Diels-Alder
      reaction with 'inverse-electron-demand' (DAR(inv)) for the construction of a
      highly efficient TMZ-BioShuttle in which TMZ is ligated to transporter and
      subcellular address molecules. The transport to the targeted nuclei resulted in
      much higher efficiency and better pharmacological effects. The reformulation of
      TMZ to TMZ-BioShuttle achieved higher in vitro killing of prostate cancer cells.
      Accordingly, the potential of TMZ for the treatment of prostate tumors was
      dramatically enhanced even in a tenfold lower concentration than applied
      normally. This TMZ-BioShuttle may be well suited for combining chemotherapy with
      other cytostatic agents or radiation therapy.

PMID- 19177420
TI  - Randomized clinical trial of visualization versus neuromonitoring of recurrent
      laryngeal nerves during thyroidectomy.
AB  - BACKGROUND: The aim of this study was to test the hypothesis that identification
      of the recurrent laryngeal nerve (RLN) during thyroid surgery reduces injury, and
      that intraoperative nerve monitoring may be of additional benefit. METHODS: One
      thousand consenting patients scheduled to have bilateral thyroid surgery were
      randomized to standard protection or additional nerve monitoring. The primary
      outcome measure was prevalence of RLN injury. RESULTS: Of 1000 nerves at risk in
      each group, transient and permanent RLN injuries were found respectively in 38
      and 12 nerves without RLN monitoring (P = 0.011) and 19 and eight nerves with RLN
      monitoring (P = 0.368). The prevalence of transient RLN paresis was lower in
      patients who had RLN monitoring by 2.9 per cent in high-risk patients (P = 0.011)
      and 0.9 per cent in low-risk patients (P = 0.249). The negative and positive
      predictive values of RLN monitoring in predicting postoperative vocal cord
      function were 98.9 and 37.8 per cent respectively. CONCLUSION: Nerve monitoring
      decreased the incidence of transient but not permanent RLN paresis compared with
      visualization alone, particularly in high-risk patients. REGISTRATION NUMBER:
      NCT00661024 (http://www.clinicaltrials.gov).

PMID- 19177422
TI  - Positron emission tomography in surveillance of head and neck squamous cell
      carcinoma after definitive chemoradiotherapy.
AB  - BACKGROUND: We assessed the role of (18)F-fluoro-deoxy-glucose positron emission
      tomography (PET) in detecting head and neck squamous cell carcinoma (HNSCC) after
      definitive chemoradiotherapy (CRT). METHODS: A prospective study presented 80 PET
      before and after CRT for 44 patients, including 44 first-time post-CRT scans
      performed between 12 and 17 weeks after radiotherapy completion, as well as 10
      repeated scans in the subsequent follow-up. PET interpretations were compared
      with clinicopathologic outcomes. RESULTS: PET demonstrated better performance
      than CT in post-CRT surveillance. Considering all 54 post-CRT PET scans,
      sensitivity for detecting primary tumors was 100%, specificity 93%, positive
      predictive value (PPV) 80%, and negative predictive value (NPV) 100%. For
      cervical diseases, sensitivity was 100%, specificity 98%, PPV 92%, and NPV 100%.
      For distant metastases, sensitivity was 100%, specificity 98%, PPV 86%, and NPV
      100%. CONCLUSIONS: Negative PET readings were reliable for predicting free of
      HNSCC and helpful for selected patients in post-CRT surveillance.

PMID- 19177423
TI  - Pseudoaneurysm of the posterior circumflex humeral artery diagnosed by
      sonography.
AB  - We report a rare case of a pseudoaneurysm of the posterior circumflex humeral
      artery, probably related to a steroid injection in the shoulder 3 months earlier.
      The clinical presentation was atypical and the location not previously described
      in the literature. The patient was referred with a painless, nonpulsatile mass in
      the posterior shoulder region and was suspected of a malignant soft-tissue tumor.
      Sonography, including power Doppler imaging, demonstrated a pseudoaneurysm, with
      the intralesional blood-filled cavity developed from the posterior circumflex
      humeral artery. The diagnosis was confirmed by pathologic examination of the
      surgical specimen.

PMID- 19177424
TI  - Cardiac amyloidosis in a patient with multiple myeloma: a case report and review
      of literature.
AB  - We report a case of a 52-year-old man with multiple myeloma and rapidly
      progressive heart failure who died unexpectedly from a probable arrhythmia.
      Postmortem examination revealed infiltrative amyloid cardiomyopathy, a rare cause
      of predominantly diastolic myocardial disease. Cardiac amyloidosis should be
      considered in any patient presenting with congestive heart failure, preserved
      systolic function, and a discrepancy between a low QRS voltage on
      electrocardiography and an apparent left ventricular hypertrophy on sonogram. The
      pattern of left ventricular diastolic dysfunction changes during the course of
      amyloidosis and the classically described restrictive physiology occurs only in
      advanced stages of the disease.

PMID- 19177425
TI  - Pitfall in the diagnosis of biliary ascariasis.

PMID- 19177426
TI  - Diagnosis of ulcerative colitis before onset of inflammation by multivariate
      modeling of genome-wide gene expression data.
AB  - BACKGROUND: Endoscopically obtained mucosal biopsies play an important role in
      the differential diagnosis between ulcerative colitis (UC) and Crohn's disease
      (CD), but in some cases where neither macroscopic nor microscopic signs of
      inflammation are present the biopsies provide only inconclusive information.
      Previous studies indicate that CD cannot be diagnosed by molecular and
      histological diagnostic tools using colonic biopsies without microscopic signs of
      inflammation, but it is unknown if this is also the case for UC. METHODS: The aim
      of the present study was to apply multivariate modeling of genome-wide gene
      expression to investigate if a diagnosable preinflammatory state exists in
      biopsies of noninflamed UC colon, and to exploit such information to build a
      diagnostic tool. RESULTS: Genome-wide gene expression data were obtained from
      control subjects and UC and CD patients. In total, 89 biopsies from 78 patients
      were included. A diagnostic model was derived with the random forest method based
      on 71 biopsies from 60 patients. The model-internal out-of-bag performance
      measure yielded perfect classification. Furthermore, the model was validated in
      independent 18 noninflamed biopsies from 18 patients (7 UC, 7 CD, 4 control)
      where the model achieved 100% sensitivity (95% confidence limits: 60.0-100) and
      100% specificity (95% confidence limits: 71.5-100). CONCLUSIONS: The present
      study demonstrates a preinflammatory state in patients diagnosed with UC. In
      addition, we demonstrate the usefulness of random forest modeling of genome-wide
      gene expression data for distinguishing quiescent and active UC colonic mucosa
      versus control and CD colonic mucosa.

PMID- 19177427
TI  - Intestinal Behcet's disease: maintenance of remission with adalimumab
      monotherapy.

PMID- 19177428
TI  - Colorectal carcinoma in indeterminate colitis.
AB  - BACKGROUND: For all the interest in the natural history of colorectal cancer
      (CRC) in ulcerative colitis (UC) and Crohn's disease (CD), surprisingly few data
      have been published regarding CRC in indeterminate colitis (IC). We present our
      experience with 15 cases of IC-associated CRC in order to assess their
      clinicopathological features and to determine their survival rates. METHODS: We
      retrospectively reviewed the medical records of patients with IC admitted to the
      Mount Sinai Hospital between 1994 and 2007 and who developed CRC. All patients
      were operated on and follow-up was complete for all patients to the closing date
      of study or to the time of death. RESULTS: A total of 19 adenocarcinomas were
      present in this series. There were 3 patients with multiple cancers; all cancers
      occurred in segments of colitis. The mean age at onset of IC was 28 years and the
      average time progression from the IC diagnosis to CRC was 19 years. Dysplasia was
      detected in 10 of the cases; 3 patients had mucinous tumors. Five patients had
      stage I tumors; 5 stage II; 4 stage III; 1 stage IV. There were 4 deaths due to
      CRC. The overall 5-year survival was 42%. CONCLUSIONS: CRC in IC shares most of
      the clinical and pathologic features as well as survival outcomes with CRC that
      occurs in the most prevalent forms of inflammatory bowel disease (IBD), UC and
      CD. Surveillance regimens currently used in the other forms of IBD seem
      applicable to IC patients as well.

PMID- 19177429
TI  - Epstein-Barr virus-associated lymphoproliferation awareness in hemophagocytic
      syndrome complicating thiopurine treatment for Crohn's disease.

PMID- 19177430
TI  - Special Series: Advances in the investigation of the structure-function
      relationship in nucleic acids and their assemblies.

PMID- 19177431
TI  - The Mental Adjustment to Cancer scale: a psychometric analysis in Spanish cancer
      patients.
AB  - OBJECTIVE: The Mental Adjustment to Cancer (MAC) scale was used to assess the
      cognitive responses to a cancer diagnosis. The aim of this study was to replicate
      the factorial structure of the Spanish version of the scale and ascertain the
      correlations between dimensions of the MAC and socio-demographic characteristics
      or medical variables. MATERIAL AND METHODS: The sample included 693 cancer
      outpatients. In order to validate the MAC questionnaire was applied a principal
      component analysis. The dimensions of the questionnaire were compared and
      correlated with socio-demographic characteristics (age and gender), medical
      variables (cancer site, time since diagnosis) and distress. RESULTS: After the
      MAC factorial analysis, 28 items were included in five factors: Hopeless,
      Anxiety, Resignation/Fatalism, Illness Acceptance and Self-Safety Behaviour. In
      relation to the variables, the women cope with cancer with more Illness
      Acceptance and Resignation subscales than men. More mature ages were related with
      Hopeless, Resignation and Self-Safety Behaviour, also correlated negatively with
      Anxiety. The cancer site showed significant differences on the Hopeless and a
      tendency on Resignation subscale. Time since diagnosis did not correlate
      significantly with any subscales in the Spanish version of the MAC. Distress was
      reflected in the Anxiety and Hopeless subscales, and moreover it was related
      negatively with Self-Safety Behaviour. CONCLUSIONS: The MAC scale was a valid and
      acceptable tool for Spanish cancer patients, however, these findings provide a
      factorial structure different from the original MAC scale.

PMID- 19177433
TI  - Architectural changes during regenerative and ontogenic liver growth in the rat.
AB  - Although liver architecture has a major impact on function, morphological aspects
      of liver growth are relatively neglected. In our recent experiments, the
      architectural changes of the rat liver were compared during 2 basic processes:
      ontogeny and regenerative liver growth. The hepatic tissue is constructed as
      structural/functional units, and probably the most established and well-defined
      such unit is the classic lobule. The extent and orientation of the lobules are
      variable in the liver, and this renders their accurate size determination more
      difficult. The filling of the liver vasculature by a colored resin nicely
      outlined the surface lobules, enabling an analysis of the alterations of these
      structures during liver growth. There are 3 structural components of postnatal
      physiological liver development: enlargement of the hepatocytes and expansion and
      multiplication of the liver lobules. However, the enlargement of the lobules is
      exclusively responsible for the regenerative liver growth following partial
      hepatectomy. The number of hepatic lobules does not change during this latter
      reaction, but they gain a more complex, irregular structure.

PMID- 19177432
TI  - Symptoms of post-traumatic stress in children with cancer: does personality trump
      health status?
AB  - OBJECTIVE: To examine the symptoms of post-traumatic stress (PTSS) in children as
      a function of health status (cancer vs healthy) and adaptive style. METHODS:
      Children with cancer (N=199) and healthy acquaintance control children (N=108)
      completed a standardized measure of PTSS. Measures of trait anxiety and
      defensiveness were obtained to characterize the adaptive style of respondents.
      RESULTS: Within the cancer group, levels of PTSS did not differ as a function of
      diagnosis, time since diagnosis, or whether children were on- or off-treatment.
      The only cancer-related factor associated with elevated PTSS was a history or
      relapse or recurrence. Children with cancer reported significantly fewer symptoms
      of re-experiencing/intrusion than did healthy children, but also reported greater
      symptoms of numbing/avoidance. However, there were no differences in total PTSS
      scores between children with cancer and controls. In contrast, a significant
      effect of adaptive style on PTSS was observed, with children identified as
      repressors or low anxious obtaining lower scores on total PTSS and all PTSS
      subscales than high-anxious children, regardless of health status. Estimates of
      the number of children meeting criteria for post-traumatic stress disorder did
      not differ between children with cancer and healthy children, and were low in
      both groups. CONCLUSIONS: Children with cancer report levels of PTSS that are not
      higher than that of their healthy peers. Personality factors such as adaptive
      style are a much more salient determinant of PTSS than is health history. These
      findings raise further questions regarding the value of a traumatic stress model
      for understanding the experiences of children with cancer.

PMID- 19177434
TI  - Using an immune functional assay to differentiate acute cellular rejection from
      recurrent hepatitis C in liver transplant patients.
AB  - In transplant recipients transplanted for hepatitis C, presentation of abnormal
      transaminases can herald the presentation of recurrent hepatitis C, cellular
      rejection, or both. Given the sometimes ambiguous histology with these 2
      entities, the ability to distinguish them is of great importance because
      misinterpretation can potentially affect graft survival. We used an immune
      functional assay to help assess the etiology of abnormal liver function test
      results in liver transplant recipients. Blood samples for the immune functional
      assay were taken from 42 recipients prospectively at various times post
      transplant and compared with clinical and histologic findings. In patients whose
      liver biopsy showed evidence of cellular rejection, the immune response was noted
      to be very high, whereas in those with active recurrence of hepatitis C, the
      immune response was found to be very low. This finding was found to be
      statistically significant (P < 0.0001). In those patients in whom there was no
      predominant histologic features suggesting 1 entity over the other, the immune
      response was higher than in those with aggressive hepatitis C but lower than in
      those with cellular rejection. In conclusion, these data show the potential
      utility of the ImmuKnow assay as a means of distinguishing hepatitis C from
      cellular rejection and its potential usefulness as a marker for outlining the
      progression of hepatitis C.

PMID- 19177436
TI  - Hepatitis B virus prevention strategies for antibody to hepatitis B core antigen
      positive liver donation: a survey of North American, European, and Asian-Pacific
      transplant programs.
AB  - Prophylactic therapy is generally used to prevent reactivated hepatitis B after
      transplantation of an antibody to hepatitis B core antigen (anti-HBc)-positive
      liver. To gain insight into current practice, a questionnaire was e-mailed to 89
      liver transplant physicians in the United States, Europe, and Asia/Australia and
      4 hepatitis B experts. Addressees were asked if they prefer lamivudine or other
      nucleoside analogs and whether these drugs are used indefinitely. They were also
      questioned about the use of hepatitis B immune globulin (HBIg), the preferred
      duration of its administration, and whether treatment strategies differ according
      to the knowledge of the serologic status of the recipient. Responses were
      obtained from 78 physicians. All transplant physicians reported the use of
      nucleoside analog therapy, and 65% prefer lamivudine (58% versus 81% for US and
      non-US physicians, P = 0.05). Sixty-one percent use HBIg (38% always, 23%
      sometimes). HBIg was used more frequently in the United States than other parts
      of the world (69% versus 46%, P = 0.03). Eighty-one percent of transplant
      physicians use nucleoside analog therapy for an indefinite period, but the
      duration of HBIg treatment varies widely. Although some centers omit nucleoside
      analog or HBIg therapy in antibody to hepatitis B surface antigen-positive
      recipients, 90% will not omit these agents if the recipient is positive for anti
      HBc alone. In conclusion, nucleoside analog therapy is nearly always used for
      anti-HBc-positive livers, and most transplant physicians treat for an indefinite
      period. Lamivudine continues to be preferred as first-line therapy. Many programs
      also use HBIg, but there is wide variation in the way this is administered.
      Further study is needed to determine the most cost-beneficial regimen.

PMID- 19177437
TI  - Upper midline incision for living donor right hepatectomy.
AB  - Innovations and refinements in the techniques of living donor right hepatectomy
      (LDRH) have been made over the past decades, but the type and size of abdominal
      incision have been at a standstill since its inception. We introduce herein the
      upper midline incision for LDRH using the standard open technique. A prospective
      case-matched study was conducted on 23 consecutive donors who underwent LDRH
      under a supraumbilical upper midline incision (I group) from February to May
      2008. These donors were matched 1:1 to 23 right liver donors with a conventional
      J-shaped incision (J group) according to age, gender, and body mass index. Under
      the mean incision length of 13.5 cm, LDRH was successfully completed in all 23
      donors without extension of the incision, with a mean operative time of 232.3 +/-
      29.2 minutes. No donors required blood transfusion during surgery. There were 2
      cases of postoperative bleeding immediately controlled under the same incision
      and a case of pleural effusion. All donors fully recovered and returned to their
      previous activities. All grafts have been functioning well. Compared with the J
      group, the I group had a shorter operative time, a shorter period of analgesic
      use, and, after discharge, infrequent complaints of wound pain. This upper
      midline incision, even without laparoscopic assistance, can be used for LDRH with
      less pain and without impairing safety, reproducibility, or effectivity, allowing
      the seemingly insufficient incision to be recommended to the transplant centers
      that are practicing living donor liver transplantation.

PMID- 19177439
TI  - Treatment of hepatitis C in liver transplant recipients.
AB  - Recurrent hepatitis C after liver transplantation is a universal phenomenon.
      Graft reinfection occurs rapidly; once it is established, allograft cirrhosis and
      decompensation rapidly ensue in many patients. Treatment with pegylated
      interferon plus ribavirin is the standard of care among nontransplant patients
      with hepatitis C; however, the applicability of these therapies in liver
      transplant patients is severely limited. Before transplantation, many patients
      are simply too ill to endure the long treatment duration necessary to achieve
      viral eradication; thus, treatment-related toxicity is a frequent barrier to
      success. Clinical trials in the pretransplantation population have yielded poor
      outcomes, with sustained virologic response rates only as high as 25%. Early
      after transplantation, treatment may be initiated prophylactically, or it may be
      initiated therapeutically in patients with evidence of recurrent disease. In
      small studies, prophylactic therapy has been associated with sustained virologic
      response rates lower than 20%, whereas in therapeutic intervention studies,
      sustained virologic response rates have ranged from 20% to 37%. In the setting of
      therapeutic intervention, preliminary indications suggest that rapid and early
      virologic response may become important clinical tools enabling the early
      identification of patients likely to respond to treatment. Two important clinical
      trials, PHOENIX (Pegasys and Copegus Administered After Liver Transplantation for
      Hepatitis C) in the prophylactic setting and PROTECT (Pegylated Interferon Alpha
      2b and Ribavirin After Orthotopic Liver Transplantation: Efficacy and Safety in
      Hepatitis C Recurrence Therapy) in the therapeutic setting, are under way and
      should further advance our understanding of the management of hepatitis C in
      patients undergoing liver transplantation.

PMID- 19177440
TI  - Splenic artery occlusion for small-for-size syndrome: better late than never but
      early is the best.

PMID- 19177438
TI  - Vascular endothelial growth factor receptor 2 expression in non-tumorous
      cirrhotic liver is higher when hepatoma is beyond Milan criteria.
AB  - Hepatocellular carcinoma (HCC) is a highly vascular tumor. Angiogenesis in HCC is
      mediated at least in part by vascular endothelial growth factor (VEGF), which is
      expressed in HCC and surrounding cirrhotic tissue. VEGF mediates its angiogenic
      effects through multiple receptors including VEGF receptor 2 (VEGFr2, KDR/FLK-1),
      The distribution and clinical significance of VEGFr2 expression in HCC and
      cirrhotic liver in the setting of liver transplantation have not been tissue site
      specific evaluated. Immunohistochemical staining for VEGFr2 was performed in 78
      liver explants from patients with HCC undergoing liver transplantation. VEGFr2
      levels in HCC were significantly increased compared to adjacent, nontumorous
      cirrhotic liver areas (P < 0.05). VEGFr2 levels were significantly higher in the
      veins and sinusoids of poorly differentiated tumors (P < 0.05). VEGFr2 levels in
      the tumors were not significantly different between patients within and beyond
      Milan criteria. However, VEGFr2 levels were significantly higher in the arteries
      of non-tumorous liver in patients beyond Milan criteria (P < 0.05). No
      significant association was observed between VEGFr2 levels and the presence of
      tumor vascular invasion or recurrence post transplantation. These findings
      suggest that VEGFr2 up-regulation is a feature of poor differentiation and tumor
      progression. Further investigation is needed to assess the value of angiogenesis
      modulation in preventing tumor formation and/or progression in cirrhotic
      patients.

PMID- 19177442
TI  - Systematic review on preventing bacterial sepsis and wound complications in liver
      transplant patients.

PMID- 19177435
TI  - Addition of adult-to-adult living donation to liver transplant programs improves
      survival but at an increased cost.
AB  - Using outcomes data from the Adult-to-Adult Living Donor Liver Transplantation
      Cohort Study, we performed a cost-effectiveness analysis exploring the costs and
      benefits of living donor liver transplantation (LDLT). A multistage Markov
      decision analysis model was developed with treatment, including medical
      management only (strategy 1), waiting list with possible deceased donor liver
      transplantation (DDLT; strategy 2), and waiting list with possible LDLT or DDLT
      (strategy 3) over 10 years. Decompensated cirrhosis with medical management
      offered survival of 2.0 quality-adjusted life years (QALYs) while costing an
      average of $65,068, waiting list with possible DDLT offered 4.4-QALY survival and
      a mean cost of $151,613, and waiting list with possible DDLT or LDLT offered 4.9
      QALY survival and a mean cost of $208,149. Strategy 2 had an incremental cost
      effectiveness ratio (ICER) of $35,976 over strategy 1, whereas strategy 3
      produced an ICER of $106,788 over strategy 2. On average, strategy 3 cost $47,693
      more per QALY than strategy 1. Both DDLT and LDLT were cost-effective compared to
      medical management of cirrhosis over our 10-year study period. The addition of
      LDLT to a standard waiting list DDLT program is effective at improving recipient
      survival and preventing waiting list deaths but at a greater cost.

PMID- 19177443
TI  - Observation of the ultrastructure of anterior cruciate ligament graft by atomic
      force microscopy.
AB  - This study presented the fibril ultrastructure of retrieved grafts from the
      reconstruction of anterior cruciate ligament (ACL) using atomic force microscopy
      (AFM). The tapping mode images of the AFM were taken from different areas of the
      longitudinally cut grafts. Regular arrangement of collagen fibrils was found in
      certain areas of the graft. In many areas, however, the fibrils were not well
      arranged in a single direction, with some smaller fibrils oriented vertically to
      larger parallel fibrils. The crossing and tangling of fibrils in ACL grafts was
      well represented in the three-dimensional AFM image. This abnormality of graft
      ultrastructure might indicate the possible alteration of the mechanical
      environment after ACL reconstruction. This study demonstrated the suitability and
      importance of ultrastructure observation of ACL grafts by AFM.

PMID- 19177441
TI  - Should liver transplantation in patients with model for end-stage liver disease
      scores <or= 14 be avoided? A decision analysis approach.
AB  - Studies have shown that liver transplantation offers no survival benefits to
      patients with Model for End-Stage Liver Disease (MELD) scores <or= 14 in
      comparison with remaining on the waitlist. The consensus of a 2003 transplant
      community national conference was that a minimum MELD score should be required
      for placement on the liver waitlist, but no minimum listing national policy was
      enacted at that time. We developed a Markov microsimulation model to compare
      results under the present US liver allocation policy with outcomes under a "Rule
      14" policy of barring patients with a MELD score of <or=14 from the waitlist or
      transplantation. For probabilities in the microsimulation model, we used data on
      all adult patients (>or=18 years) listed for or undergoing primary liver
      transplantation in the United States for chronic liver disease from 1/1/2003
      through 12/31/2007 with follow-up until 2/1/2008. The "Rule 14" policy gave a 3%
      improvement in overall patient survival over the present system at 1, 2, 3, and 4
      years and predicted a 13% decrease in overall waitlist time for patients with
      MELD scores of 15 to 40. Patients with the greatest benefit from a "Rule 14"
      policy were those with MELD scores of 6 to 10, for whom a 17% survival advantage
      was predicted from waiting on the list versus undergoing transplantation. Our
      analysis supports changing the national liver allocation policy to not allow
      liver transplantation for patients with MELD <or= 14.

PMID- 19177444
TI  - Successful treatment of cerebral tuberculosis in a liver transplant recipient.

PMID- 19177445
TI  - Peroral cholangioscopy-guided stricture therapy in living donor liver
      transplantation.

PMID- 19177446
TI  - Impact of preoperative overt hepatic encephalopathy on neurocognitive function
      after liver transplantation.
AB  - In the current Model for End-Stage Liver Disease allocation system, patients are
      at risk of suffering repeated episodes of hepatic encephalopathy (HE) while
      waiting for an orthotopic liver transplantation (OLT); the posttransplantation
      impact of these episodes has not been well explored. We evaluated the cognitive
      function and quality of life in a group of OLT recipients (n = 25) who had
      suffered from overt HE prior to their procedure (HE-PreLT group) and compared
      their performance to that of a similar group of patients (n = 14) without overt
      HE (No HE-PreLT group) as well as to controls. Patients were selected from a
      cohort of 280 patients who underwent OLT during this period; the presence of
      clinical confounders excluded many of the remaining subjects. Demographic and
      clinical characteristics were balanced among groups. At an average of 18 months
      after OLT, we administered 2 neuropsychological batteries [Psychometric Hepatic
      Encephalopathy Score (PHES) test battery and Repeatable Battery for the
      Assessment of Neuropsychological Status (RBANS)]; a pyschophysiological test
      (critical flicker frequency); and the SF-36 quality of life score. The HE-PreLT
      group scored below controls in 5 of 6 cognitive domains tested by RBANS, 3 of 6
      PHES subtests, as well as the critical flicker frequency test. The No HE-PreLT
      group scored below the controls in 1 of the 6 cognitive domains tested by RBANS.
      The more severe neurocognitive abnormalities seen in the HE-PreLT group did not
      appear to affect quality of life, as lower values than normative data were only
      found in 1 of the 8 SF-36 scales. In conclusion, neurocognitive abnormalities
      were more severe in liver transplant recipients that had suffered from overt HE
      prior to OLT. Prospective studies of neurocognitive function pre-OLT and post-OLT
      are needed to fully determine the impact of such abnormalities.

PMID- 19177447
TI  - Delayed splenic artery occlusion for treatment of established small-for-size
      syndrome after partial liver transplantation.
AB  - We looked at the impact of delayed splenic artery occlusion (SAO) on recipients
      with established small-for-size syndrome (SFSS) after partial graft liver
      transplantation [either from a living donor (LD) or split from a deceased donor
      (DD)]. Between 1999 and 2007 we performed a total of 100 partial liver
      transplantations in adult recipients: 66 LD transplantations and 34 DD split
      transplantations. Of these, 7 (7%) developed SFSS, diagnosed by the clinical
      features of cholestasis, coagulopathy, and ascites. Mean graft weight/recipient
      weight (GW/RW) ratio in these 7 recipients was 0.94%. Five of these 7 recipients
      underwent relaparotomy at a mean of 10 days post-transplantation to rule out a
      technical complication, and then intraoperative splenic artery ligation was
      performed. The other 2 recipients were treated radiologically by splenic artery
      coiling-at 9 and 13 days post-transplantation. Median serum bilirubin at the time
      of the splenic artery procedure was 20 mg/dL; by 3 weeks postprocedure this had
      decreased to 2.5 mg/dL. Of the 7 recipients with SFSS, 6 improved and eventually
      obtained normal graft function; 1 recipient did not improve and ultimately
      underwent retransplantation because of persistent cholestasis and failure to
      thrive. Delayed SAO represents a potential option for the treatment of recipients
      with established SFSS after partial liver transplantation.

PMID- 19177448
TI  - The importance of hepatic encephalopathy: pre-transplant and post-transplant.

PMID- 19177449
TI  - Pharmacokinetics, efficacy, and safety of mycophenolate mofetil in combination
      with standard-dose or reduced-dose tacrolimus in liver transplant recipients.
AB  - The pharmacokinetics of mycophenolate mofetil (MMF) in liver transplant
      recipients may change because of pharmacokinetic interactions with coadministered
      immunosuppressants or because changes in the enterohepatic anatomy may affect
      biotransformation of MMF to mycophenolic acid (MPA) and enterohepatic
      recirculation of MPA through the hydrolysis of mycophenolate acid glucuronide to
      MPA in the gut. In the latter case, the choice of formulation (oral versus
      intravenous) could have important clinical implications. We randomized liver
      transplant patients (n = 60) to standard (10-15 ng/mL) or reduced (5-8 ng/mL)
      trough levels of tacrolimus plus intravenous MMF followed by oral MMF (1 g twice
      daily) with corticosteroids. Pharmacokinetic sampling was performed after the
      last intravenous MMF dose, after the first oral MMF dose, and at selected times
      over 52 weeks. The efficacy and safety of the 2 regimens were also assessed.
      Twenty-eight and 27 patients in the tacrolimus standard-dose and reduced-dose
      groups, respectively, were evaluated. No significant differences between the
      tacrolimus standard-dose and reduced-dose groups were seen in dose-normalized MPA
      values of the time to the maximum plasma concentration (1.25 versus 1.28 hours),
      the maximum plasma concentration (15.5 +/- 7.93 versus 13.6 +/- 7.03 microg/mL),
      or the area under the concentration-time curve from 0 to 12 hours (AUC(0-12);
      53.0 +/- 20.6 versus 43.8 +/- 15.5 microg h/mL) at week 26 or at any other time
      point. No relationship was observed between the tacrolimus trough or AUC(0-12)
      and MPA AUC(0-12). Exposure to MPA after oral and intravenous administration was
      similar. Safety and efficacy were similar in the two treatment groups. In
      conclusion, exposure to MPA is not a function of exposure to tacrolimus. The
      similar safety and efficacy seen with MMF plus standard or reduced doses of
      tacrolimus suggest that MMF could be combined with reduced doses of tacrolimus.

PMID- 19177451
TI  - Significant correlation between spleen volume and thrombocytopenia in liver
      transplant patients: a concept for predicting persistent thrombocytopenia.
AB  - Interferon (IFN) therapy with or without ribavirin treatment is well established
      as a standard antiviral treatment for hepatitis C virus (HCV)-infected patients.
      However, susceptibility to thrombocytopenia is a major obstacle for initiating or
      continuing this therapy, particularly in liver transplant (LTx) recipients with
      HCV. Studies have reported that splenectomy performed concurrently with LTx is a
      feasible strategy for conditioning patients for anti-HCV IFN therapy. However,
      the relationship between the severity of splenomegaly and alterations in the
      blood cytopenia in LTx recipients remains to be clarified. Here, we analyzed the
      relationship between spleen volume (SV) and thrombocytopenia in 45 patients who
      underwent LTx at Hiroshima University Hospital. The extent of pre-LTx
      splenomegaly [the SV to body surface area (BSA) ratio in an individual] was
      inversely correlated with both the post-LTx white blood cell count and platelet
      (PLT) count (P < 0.001). Furthermore, the PLT count of patients with
      thrombocytopenia (PLT count <or= 5 x 10(4)/mm(3)) increased significantly in the
      group without splenomegaly (SV/BSA value < 400) versus that in the group with
      splenomegaly (P = 0.005). Thus, if both splenomegaly and thrombocytopenia coexist
      (PLT count <or= 5 x 10(4)/mm(3) and SV/BSA value >or= 400), persistent
      thrombocytopenia is predictable after LTx.

PMID- 19177450
TI  - Overexpression of indoleamine dioxygenase in rat liver allografts using a high
      efficiency adeno-associated virus vector does not prevent acute rejection.
AB  - The aim of this study was to evaluate the ability of local overexpression of
      indoleamine dioxygenase (IDO) to abrogate rat liver transplant rejection by the
      use of an adeno-associated virus vector [recombinant adeno-associated virus 2/8
      (rAAV2/8)] to deliver the transgene to the allograft prior to transplantation. A
      green fluorescent protein (GFP)-expressing vector [recombinant adeno-associated
      virus 2/8-liver-specific promoter 1-enhanced green fluorescent protein (rAAV2/8
      LSP1-eGFP)] was used to examine the kinetics of expression and optimal dosing for
      transduction of Piebald Virol Glaxo (PVG) rat livers. A vector encoding the rat
      IDO gene (rAAV2/8-LSP1-rIDO) was constructed and tested by its ability to induce
      tryptophan catabolism and kynurenine production in vitro and in vivo. PVG donor
      rats were injected, via the portal vein, with rAAV2/8-LSP1-rIDO 2 weeks before
      transplantation into PVG strain isograft or Lewis (LEW) strain allograft
      recipients. With the enhanced GFP vector, 29.5% and 47.4% of hepatocytes were
      found to express GFP at 3 and 6 weeks after injection, respectively. In
      untransplanted PVG animals, the rAAV2/8-LSP1-rIDO vector induced, 3 weeks after
      administration, a 1.8-fold increase (P = 0.0161) in liver IDO activity, which was
      associated with a fall in serum tryptophan to 0.5 times the baseline level (P <
      0.001). PVG recipients of PVG liver isografts pretreated with the IDO-expressing
      vector had a 45% lower level of serum tryptophan than recipients of isografts
      pretreated with the GFP-expressing vector (P = 0.03). LEW recipients of PVG liver
      allografts pretreated with the rat IDO vector had a median survival time of 12
      days, whereas recipients of allografts pretreated with rAAV2/8-LSP1-eGFP had a
      median survival time of 13 days (P = 0.38). Both groups displayed similar
      histological features of acute cellular rejection. In conclusion, rAAV2/8 vectors
      produce highly efficient, though delayed, hepatocyte transduction in vivo and
      provide a useful gene delivery tool for transplantation models. However, gene
      delivery using IDO was unsuccessful in prolonging rat liver allograft survival.

PMID- 19177452
TI  - Pediatric liver retransplantation: outcomes and a prognostic scoring tool.
AB  - Nine to twenty-nine percent of pediatric liver transplant recipients require
      retransplantation. No previous pediatric study has proposed a prognostic scoring
      system. We have used the United Network for Organ Sharing transplantation
      database to conduct a retrospective cohort study of patients who were less than
      18 years of age when they received their retransplant (n = 1130). Using a random
      two-thirds of the subjects, we developed a prognostic scoring system by
      performing a multivariate Cox analysis with non-laboratory clinical
      characteristics. The scoring system was verified in the remaining one-third of
      the subjects. Stratifying the verification group into risk groups by prognostic
      score demonstrated its predictive value. Those in the low-risk category had
      survival similar to that of primary liver transplant recipients. Those in the
      high-risk category had 2.4 (95% confidence interval: 1.6-3.7) times the risk of
      death or retransplantation as those in the low-risk category. Risk factors in the
      scoring system included being on life support at the time of retransplant,
      receiving a split liver graft, and having an original diagnosis of neonatal
      cholestasis, familial cholestasis, paucity of bile ducts, or congenital
      abnormalities. Protective factors in the scoring system included older age at the
      time of transplantation and having acute rejection contribute to graft failure.
      In conclusion, with simple clinical characteristics, this scoring tool can
      modestly discriminate between those children at high risk and those children at
      low risk of poor outcome after liver retransplantation.

PMID- 19177453
TI  - PCR/LDR/capillary electrophoresis for detection of single-nucleotide differences
      between fetal and maternal DNA in maternal plasma.
AB  - BACKGROUND: The discovery of fetal DNA in maternal plasma has opened up an
      approach for noninvasive diagnosis. We have now assessed the possibility of
      detecting single-nucleotide differences between fetal and maternal DNA in
      maternal plasma by polymerase chain reaction (PCR)/ligase detection
      reaction((LDR)/capillary electrophoresis. METHODS: PCR/LDR/capillary
      electrophoresis was applied to detect the genotype of c.454-397T>gene (ESR1) from
      experimental DNA models of maternal plasma at different sensitivity levels and 13
      maternal plasma samples.alphaC in estrogen receptor. RESULTS: (1) Our results
      demonstrated that the technique could discriminate low abundance single
      nucleotide mutation with a mutant/normal allele ratio up to 1:10 000. (2)
      Examination of ESR1 c.454-397T>C genotypes by using the method of restriction
      fragment length analysis was performed in 25 pregnant women, of whom 13 pregnant
      women had homozygous genotypes. The c.454-397T>C genotypes of paternally
      inherited fetal DNA in maternal plasma of these 13 women were detected by
      PCR/LDR/capillary electrophoresis, which were accordant with the results of
      umbilical cord blood. CONCLUSIONS: PCR/LDR/capillary electrophoresis has very
      high sensitivity to distinguish low abundance single nucleotide differences and
      can discriminate point mutations and single-nucleotide polymorphisms(SNPs) of
      paternally inherited fetal DNA in maternal plasma.

PMID- 19177454
TI  - Isolated fetal umbilical vein varix--prenatal sonographic diagnosis and suggested
      management.
AB  - OBJECTIVE: To present our experience with fetuses with umbilical vein varix
      (UVV), to investigate possible risk factors and to suggest a management scheme of
      evaluation. STUDY DESIGN: A study of 14 pregnancies complicated with isolated UVV
      was performed. Data collected included sonographic characteristics of the UVV,
      pregnancy outcome including induction of labour, mode of delivery, birthweight,
      and neonatal complications. RESULTS: UVV was diagnosed at a median gestational
      age of 27.5 weeks' gestation (range: 22-34 weeks). The average diameter of the
      UVV at diagnosis was 10.6 mm (range: 8-15 mm), and the maximal diameter during
      follow-up was 12.8 mm (range: 10-18 mm). The median gestational age at delivery
      was 36.1 weeks (range: 34-40 weeks), with an average birthweight of 2834 g
      (range: 1725-3715 g). Five women underwent emergent cesarean section. In fetuses
      with turbulent flow in the UVV there was a tendency to larger maximal sizes of
      the UVV, earlier gestational age at delivery and smaller birthweight. There were
      no cases of fetal or neonatal demise. CONCLUSIONS: We suggest that fetuses with
      UVV should be followed weekly from diagnosis to 28 weeks, and twice a week
      afterwards. Induction of labour should be considered at 36-37 weeks' gestation or
      at signs of fetal distress.

PMID- 19177455
TI  - The full spectrum of holoprosencephaly-associated mutations within the ZIC2 gene
      in humans predicts loss-of-function as the predominant disease mechanism.
AB  - Mutations of the ZIC2 transcription factor gene are among the most common
      heterozygous variations detected in holoprosencephaly (HPE) patients, a patient
      group who lack critical midline forebrain specification due to defective
      embryonic signaling during development. Recent studies indicate that complete
      deficiency of the related murine Zic2 transcription factor can also be a
      contributing factor to variable midline deficiencies, presenting during mid
      gastrulation, that could explain similar forebrain anomalies in this model
      system. Here we collect and summarize all available mutations in the human ZIC2
      gene detected in HPE patients (21 published and 62 novel). Our analysis
      corroborates this mechanism proposed in mice by predicting loss-of-function as
      the likely pathogenetic mechanism common to most, if not all, of these mutations
      in HPE.

PMID- 19177456
TI  - S-adenosylhomocysteine hydrolase (AHCY) deficiency: two novel mutations with
      lethal outcome.
AB  - This paper reports studies of two novel, allelic missense mutations found in the
      S-adenosylhomocysteine hydrolase (AHCY) gene from a new case of AHCY deficiency
      in an infant girl who died at age four months. The mutations lead to replacement
      of arginine with cysteine (p.Arg49Cys) and aspartic acid with glycine
      (p.Asp86Gly). Functional analysis of recombinant proteins containing the
      mutations detected showed that both dramatically reduce AHCY activity. The
      p.Arg49Cys mutant protein forms intermolecular disulphide bonds, leading to
      macromolecular structures that can be prevented by reducing agent DTT. The
      p.Asp86Gly protein tends to form enzymatically inactive aggregates and the loss
      of a single negative charge as a result of the mutation is involved in enzyme
      inactivation. We show that replacing Gly86 with negatively charged Glu86 in
      mutant protein restores enzymatic activity to 70% of wild-type, whereas changing
      Gly86 to positively charged Lys86 or uncharged Leu86 does not improve enzyme
      activity, indicating that the negative charge is important for maintenance of
      such activity. These studies significantly extend knowledge about the importance
      of residue 86 for AHCY activity. Residue 86 has not been implicated before in
      this way and the results suggest that the present model of S-
      adenosylhomocysteine (AdoHcy) hydrolysis may need refinement. Our functional
      studies provide novel insight into the molecular defect underlying AHCY
      deficiency and reveal that both low enzyme activity and protein stability of AHCY
      contribute to the clinical phenotype.

PMID- 19177457
TI  - Multiple endocrine neoplasia type 2 RET protooncogene database: repository of
      MEN2-associated RET sequence variation and reference for genotype/phenotype
      correlations.
AB  - Multiple endocrine neoplasia type 2 (MEN2) is an inherited, autosomal-dominant
      disorder caused by deleterious mutations within the RET protooncogene. MEN2 RET
      mutations are mainly heterozygous, missense sequence changes found in RET exons
      10, 11, and 13-16. Our group has developed the publicly available, searchable
      MEN2 RET database to aid in genotype/phenotype correlations, using Human Genome
      Variation Society recommendations for sequence variation nomenclature and
      database content. The MEN2 RET database catalogs all RET sequence variation
      relevant to the MEN2 syndromes, with associated clinical information. Each
      database entry lists a RET sequence variation's location within the RET gene,
      genotype, pathogenicity classification, MEN2 phenotype, first literature
      reference, and comments (which may contain information on other clinical
      features, complex genotypes, and additional literature references). The MEN2
      phenotype definitions were derived from the International RET Mutation Consortium
      guidelines for classification of MEN2 disease phenotypes. Although nearly all of
      the 132 RET sequence variation entries initially cataloged in the database were
      from literature reports, novel sequence variation and updated phenotypic
      information for any existing database entry can be submitted electronically on
      the database website. The database website also contains links to selected MEN2
      literature reviews, gene and protein information, and RET reference sequences.
      The MEN2 RET database (www.arup.utah.edu/database/MEN2/MEN2_welcome.php) will
      serve as a repository for MEN2-associated RET sequence variation and reference
      for RET genotype/MEN2 phenotype correlations.

PMID- 19177458
TI  - Ultrasound prediction of intertwin birth weight discordance in monochorionic
      diamniotic twin pregnancies.
AB  - OBJECTIVES: To estimate the accuracy of ultrasound to predict birth weight (BW)
      and BW discordance in monochorionic diamniotic (MCDA) twin pregnancies. METHODS:
      A prospective series of MCDA twin pregnancies was subjected to ultrasound fetal
      weight estimations (EFW) at 16, 20, and 26 weeks of gestation and within 2 weeks
      of birth. Intertwin weight discordance (DeltaEFW and DeltaBW) was calculated. The
      correlation between DeltaEFW, DeltaBW, EFW, and BW was assessed (Pearson) and
      least square regression analysis was performed. Positive and negative predictive
      values of ultrasound to detect severe DeltaBW were calculated. Receiver-operating
      characteristics (ROC) curves were constructed to predict DeltaBW >25% at
      different time points of gestation. RESULTS: Sixty pregnancies were included.
      Median DeltaBW was 9.98%. Ten(16,7%), 8(13,3%) and 5(8,3%) twin pairs had a
      DeltaBW >20%, >25% and >30%, respectively. BW and EFW (r = 0.96; p < 0.001) as
      well as DeltaBW and DeltaEFW were well correlated with each other (r = 0.75; p <
      0.001). Bland-Altman analysis showed that ultrasound evaluation overestimated
      DeltaBW if >20%. Negative predictive value of ultrasound for DeltaBW >25% was
      98%. The area under the curve (AUC) to predict a DeltaBW >25% at 16, 20, and 26
      weeks and <2 weeks before birth was 0.79, 0.87, 0.93, and 0.95, respectively.
      CONCLUSIONS: Ultrasound estimations of BW and DeltaBW are highly correlated with
      actual BW and DeltaBW in MCDA twin pregnancies.

PMID- 19177459
TI  - Recurrence of Galloway Mowat syndrome and associated prenatal imaging findings.

PMID- 19177461
TI  - Psychological factors and preferences for communicating prognosis in esophageal
      cancer patients.
AB  - OBJECTIVE: Discussing prognosis is often confronting and complex for cancer
      patients. This study investigates how patients' psychological characteristics
      relate to their preferences concerning the disclosure of prognosis. METHODS: One
      hundred and seventy-six esophageal cancer patients participated in the study.
      They had undergone esophagectomy within the past 28 months and did not have
      evidence of cancer recurrence. Patients completed a questionnaire eliciting their
      preferences for prognostic information. Sociodemographic characteristics,
      involvement preferences, anxiety, depression, fear of recurrence, striving for
      quality of life (QOL) or quantity of life and trust in physicians were explored
      as predictors for (a) wanting to be informed about prognosis and (b) the
      initiation of discussion about prognosis. RESULTS: Patients wanting all
      prognostic information had more fear for the disease to recur (p<0.05) and were
      inclined to be more actively involved during consultation (p<0.001). Post hoc
      analyses showed that patients with worse QOL scores reported more fear of
      recurrence. Anxiety, depression, trust and tendency to strive for QOL or quantity
      of life were not related to preferences concerning prognostic information.
      CONCLUSIONS: The more fear patients have for esophageal cancer to recur, the more
      information they want about prognosis. Thus, patient's fear for recurrent disease
      is not a reason for withholding prognostic information. Results also suggest that
      there is no harm in asking patients what information they want.

PMID- 19177462
TI  - Identification of urinary soluble E-cadherin as a novel biomarker for diabetic
      nephropathy.
AB  - BACKGROUND: Currently, early diagnosis of diabetic nephropathy (DN) remains a
      major challenge. Thus, more investigations into new DN-related biomarkers are
      needed. METHODS: We employed urinary proteomic approach of fluorescence-based
      difference gel electrophoresis (DIGE) and mass spectrometry to identify novel
      biomarkers in urine samples, which were from type 2 diabetes patients with
      normoalbuminuria (DM group), microalbuminuria (DN1 group), macroalbuminuria (DN2
      group) and control group (n=8 in each group). The identified biomarker was
      further studied by western blot in urine samples (n=6 in each group) and
      immunohistochemistry in renal biopsies. Besides, the urinary level of biomarker
      was detected and analyzed using enzyme-linked immunosorbent assay(ELISA) method
      (n=40 in each group). RESULTS: A novel DN-related biomarker, urinary E-cadherin,
      was identified by proteomic methods, which up-regulated 1.3-fold, 5.2-fold and
      8.5-fold in DM, DN1 and DN2 groups compared with control group. Meanwhile, high
      expression of urinary soluble 80 kDa fragment of E-cadherin (sE-cadherin) was
      verified in DN groups by western blot. The ELISA data also demonstrated that
      urinary sE-cadherin-to-creatinine ratio was significantly increased in DN1 and
      DN2 groups versus DM group or control group (2751.5+/-164 and 5839.6+/-428 vs
      721.9+/-93 or 652.7+/-87 microg/g; p<0.001). The sensitivity and specificity of
      urinary sE-cadherin for diagnosis of DN were calculated as 78.8% (95% CI, 74-83%)
      and 80% (95% CI, 65-91%). Besides, immunohistochemical stain showed that E
      cadherin expression was markedly decreased in renal tubular epithelial cells of
      patients with DN versus healthy controls. CONCLUSIONS: Urinary sE-cadherin has a
      potential clinical diagnostic value for DN and E-cadherin may participate in the
      pathogenesis of DN.

PMID- 19177463
TI  - Mechanical compression of articular cartilage induces chondrocyte proliferation
      and inhibits proteoglycan synthesis by activation of the ERK pathway:
      implications for tissue engineering and regenerative medicine.
AB  - Articular cartilage is recalcitrant to endogenous repair and regeneration and is
      thus a focus of tissue engineering and regenerative medicine strategies. A
      prerequisite for articular cartilage tissue engineering is an understanding of
      the signal transduction pathways involved in mechanical compression during trauma
      or disease. We sought to explore the role of the extracellular signal-regulated
      kinase 1/2 (ERK 1/2) pathway in chondrocyte proliferation and proteoglycan
      synthesis following acute mechanical compression. Bovine articular cartilage
      explants were cultured with and without the ERK 1/2 pathway inhibitor PD98059.
      Cartilage explants were statically loaded to 40% strain at a strain rate of 1/s
      for 5 s. Control explants were cultured under similar conditions but were not
      loaded. There were four experimental groups: (a) no load, without inhibitor; (b)
      no load, with the inhibitor PD98059; (c) loaded, without the inhibitor; and (d)
      loaded, with the inhibitor PD98059. The explants were cultured for varying
      durations from 5 min to 5 days and were then analysed by biochemical and
      immunohistochemical methods. Mechanical compression induced phosphorylation of
      ERK 1/2, and this was attenuated with the ERK 1/2 pathway inhibitor PD98059 in a
      dose-dependent manner. Chondrocyte proliferation was increased by mechanical
      compression. This effect was blocked by the inhibitor of the ERK 1/2 pathway.
      Mechanical compression also led to a decrease in proteoglycan synthesis that was
      reversed with inhibitor PD98059. In conclusion, the ERK 1/2 pathway is involved
      in the proliferative and biosynthetic response of chondrocytes following acute
      static mechanical compression.

PMID- 19177464
TI  - Reliability and validity of the Japanese version of the Short-form Supportive
      Care Needs Survey questionnaire (SCNS-SF34-J).
AB  - PURPOSE: Provision of supportive care to meet patients' individual needs is
      instrumental to enhancing their quality of life. We therefore need an appropriate
      assessment tool to measure such needs. The purpose of this study was to examine
      the psychometric property of the Japanese version of the Short-form Supportive
      Care Needs Survey questionnaire (SCNS-SF34-J). SUBJECTS AND METHODS: The forward
      backward translation method was used to develop the Japanese version of SCNS
      SF34, originally developed by Boyes et al. in Australia. Randomly selected
      ambulatory female patients with breast cancer participated in this study. They
      were asked to complete the SCNS-SF34-J and the European Organization for Research
      and Treatment of Cancer QLQ-C 30. The validity and the reliability of SCNS-SF34-J
      were evaluated statistically. RESULTS: Complete data were available from 408
      patients. A five-factor solution that accounted for 74.6% of the total variance
      was reproduced. The results confirmed the five-factor structure found in the
      original SCNS development study, consisting of Health system and Information
      needs, Psychological needs, Physical needs, Care and Support needs, and Sexuality
      needs. Cronbach's alpha coefficients, which are the measures of the internal
      consistency, were above 0.85 for all of five subscales. Significant correlations
      were also found for corresponding subscales in each of the instruments. The
      anticipated differences in supportive care needs between groups divided by the
      patient characteristics, such as the disease stage, were found to be significant.
      CONCLUSION: The results indicated that SCNS-SF34-J is a valid and reliable tool
      for assessing the supportive care needs of Japanese cancer patients.

PMID- 19177465
TI  - Old concepts, current knowledge, new challenges.

PMID- 19177467
TI  - Lessons from STEP-BD for the treatment of bipolar depression.

PMID- 19177468
TI  - Chelation therapy for neurodegenerative diseases.
AB  - Mounting evidence suggests a central role for transition biometals in the
      etiopathogenesis of neurodegenerative diseases (ND). Indeed, while studying the
      molecular basis for this heterogeneous group of diseases, it has become
      increasingly evident that biometals and nonphysiological Al are often involved in
      pathology onset and progression, either by affecting the conformation of specific
      proteins or by exacerbating local oxidative stress. The apparently critical role
      played by metal dishomeostasis in ND makes chelation therapy an attractive
      pharmacological option. However, classical metal chelation approaches, relying on
      potent metal ligands, turned out to be successful only in those rare cases where
      exceptional brain metal accumulation occurs due to specific defects in metal
      metabolism. In contrast, metal-targeted approaches using ligand of intermediate
      strength seem to be more appropriate in fighting the major ND, although their
      benefits are still questioned. We report here a survey of recent evidences
      supporting the use of a variety of metal ligands, and even functionalized
      nanoparticles, for the treatment of the most common ND. The beneficial
      neuropharmacological actions of metal-targeted agents most likely arise from
      local metal redistribution rather than from massive metal removal. The
      perspectives for the development of new effective agents against ND are
      critically discussed.

PMID- 19177469
TI  - Hospitalization in Winnipeg, Canada due to occupational disease: a pilot study.
AB  - BACKGROUND: The objectives of this study were to identify the extent of
      occupational exposures to hazardous substances amongst male medical inpatients
      and to determine the extent to which these exposures may have contributed to the
      development of medical conditions. METHODS: A random sample of 297 male who were
      admitted from outside the hospital to the medical wards to a large tertiary care
      hospital, were between age 18-75 and could communicate in English completed an
      occupational history questionnaire. This information was merged with an inpatient
      database which contained patient demographics, admission diagnoses, and co
      morbidity data. A specialist in occupational medicine and internal medicine
      determined whether the medical conditions the participants had were related to
      their exposures. RESULTS: One individual had a condition causing admission that
      was related to his work and 12 others (4%) had a condition that was possibly
      related to their work which had caused symptoms. One additional individual was
      found to have asymptomatic asbestos related pleural fibrosis. Fourteen of 37
      possible harmful occupational exposures were reported by more than 10% of the
      study participants. On average each participant reported 5.5 exposures.
      CONCLUSIONS: Occupational exposures to male medical inpatients are common. For
      4.4% (13/297) of male admissions to the general medical wards from the emergency
      room occupational factors may have played a role in the development of medical
      conditions which led to admission or to major co-morbidities. Detailed
      occupational histories will likely lead to more suspected cases of work related
      medical admissions.

PMID- 19177471
TI  - Acetaminophen prevents aging-associated hyperglycemia in aged rats: effect of
      aging-associated hyperactivation of p38-MAPK and ERK1/2.
AB  - BACKGROUND: Aging-related hyperglycemia is associated with increased oxidative
      stress and diminished muscle glucose transporter-4 (Glut4) that may be regulated,
      at least in part, by the mitogen-activated protein kinases (MAPK). METHODS: To
      test the possibility that aging-related hyperglycemia can be prevented by
      pharmacological manipulation of MAPK hyperactivation, aged (27-month old) Fischer
      344/NNiaHSD x Brown Norway/BiNia F1 (F344BN) rats were administered acetaminophen
      (30 mg/kg body weight/day) for 6 months in drinking water. RESULTS: Hepatic
      histopathology, serum aspartate aminotransferase and alanine aminotransferase
      analyses suggested that chronic acetaminophen did not cause hepatotoxicity.
      Compared with adult (6-month) and aged (27-month) rats, very aged rats (33-month)
      had higher levels of blood glucose, phosphorylation of soleus p38-MAPK and
      extracellular-regulated kinase 1/2 (ERK1/2), superoxide and oxidatively modified
      proteins (p<0.05), and these changes were associated with decreased soleus Glut4
      protein abundance (p<0.05). Chronic acetaminophen treatment attenuated age
      associated increase in blood glucose by 61.3% (p<0.05) and increased soleus Glut4
      protein by 157.2% (p<0.05). These changes were accompanied by diminished
      superoxide levels, decrease in oxidatively modified proteins (-60.8%; p<0.05) and
      reduced p38-MAPK and ERK1/2 hyperactivation (-50.4% and -35.4%, respectively;
      p<0.05). CONCLUSIONS: These results suggest that acetaminophen may be useful for
      the treatment of age-associated hyperglycemia.

PMID- 19177472
TI  - Influence of molecular parameters and increasing magnetic field strength on
      relaxivity of gadolinium- and manganese-based T1 contrast agents.
AB  - Simulations were performed to understand the relative contributions of molecular
      parameters to longitudinal (r(1)) and transverse (r(2)) relaxivity as a function
      of applied field, and to obtain theoretical relaxivity maxima over a range of
      fields to appreciate what relaxivities can be achieved experimentally. The field
      dependent relaxivities of a panel of gadolinium and manganese complexes with
      different molecular parameters, water exchange rates, rotational correlation
      times, hydration state, etc. were measured to confirm that measured relaxivities
      were consistent with theory. The design tenets previously stressed for optimizing
      r(1) at low fields (very slow rotational motion; chelate immobilized by protein
      binding; optimized water exchange rate) do not apply at higher fields. At 1.5 T
      and higher fields, an intermediate rotational correlation time is desired (0.5-4
      ns), while water exchange rate is not as critical to achieving a high r(1). For
      targeted applications it is recommended to tether a multimer of metal chelates to
      a protein-targeting group via a long flexible linker to decouple the slow motion
      of the protein from the water(s) bound to the metal ions. Per ion relaxivities of
      80, 45, and 18 mM(-1) s(-1) at 1.5, 3 and 9.4 T, respectively, are feasible for
      Gd(3+) and Mn(2+) complexes.

PMID- 19177473
TI  - In silico screening for PTPN22 inhibitors: active hits from an inactive
      phosphatase conformation.
AB  - A gain-of-function mutant of the lymphoid phosphatase Lyp (PTPN22) has recently
      been implicated in type 1 diabetes and other autoimmune diseases, suggesting that
      small-molecule inhibitors of Lyp could be useful for the treatment of
      autoimmunity. Virtual ligand screening (VLS) was applied in the search for hit
      compounds. Two different docking algorithms, FlexX and ICM, were used to screen a
      library of 'drug-like' molecules against two different 3D structures,
      representing the catalytic site of Lyp in both the inactive 'open' and active
      'closed' conformations. The top-scoring compounds of each VLS run were tested for
      their inhibitory activity against recombinant Lyp. Interestingly, VLS with both
      active and inactive conformations yielded very potent hits, with IC(50) values in
      the sub- and low-micromolar range. Moreover, many of these hits showed high
      docking scores only with one conformation. For instance, this was the case with
      several 2-benzamidobenzoic acid derivatives, which specifically docked into the
      inactive open form. Tryptophan fluorescence measurements further support a
      binding mode in which these compounds seem to stabilize the phosphatase in its
      inactive conformation.

PMID- 19177474
TI  - "Helter-skelter-like" perylene polyisocyanopeptides.
AB  - Exciton migration! Spectroscopic analyses and extensive molecular dynamics
      studies revealed a well-defined 4(1) helix in which the perylene molecules (see
      figure) form four "helter-skelter-like" overlapping pathways along which excitons
      and electrons can rapidly migrate.We report on a combined experimental and
      computational investigation on the synthesis and thorough characterization of the
      structure of perylene-functionalized polyisocyanides. Spectroscopic analyses and
      extensive molecular dynamics studies revealed a well defined 4(1) helix in which
      the perylene molecules form four "helter skelter-like" overlapping pathways along
      which excitons and electrons can rapidly migrate. The well-defined polymer
      scaffold stabilized by hydrogen bonding, to which the chromophores are attached,
      accounts for the precise architectural definition, and molecular stiffness
      observed for these molecules. Molecular-dynamics studies showed that the
      chirality present in these polymers is expressed in the formation of stable right
      handed helices. The formation of chiral supramolecular structures is further
      supported by the measured and calculated bisignated Cotton effect. The structural
      definition of the chromophores aligned in one direction along the backbone is
      highlighted by the extremely efficient exciton migration rates and charge
      densities measured with Transient Absorption Spectroscopy.

PMID- 19177475
TI  - B values as a sensitive measure of steric effects.
AB  - Someone who says "A" should be prepared to also say "B": In contrast to
      cyclohexane model-based A values, biphenyl model-derived B values are powerful
      tools to quantify steric repulsion in and conformational behavior of ortho
      substituted aromatic compounds.Torsional barriers of 15 ortho-substituted
      biphenyls have been determined computationally using the B3LYP density functional
      and experimentally by variable-temperature ("dynamic") nuclear magnetic
      resonance. Taking advantage of the 3'-isopropyldimethylsilyl group as a novel and
      superior diastereotopicity probe and tracking coalescence temperatures down to 
      173 degrees C (100 K), activation energies of aryl-aryl rotation as small as 5
      kcal mol(-1) can be assessed. The 2-X/2'-H repulsion increments thus derived are
      powerful parameters for rationalizing and predicting the conformational behavior
      of aromatic compounds carrying ortho substituents.

PMID- 19177476
TI  - The structure of (SCN)(x): a study using molecular and solid-state density
      functional theory calculations.
AB  - A riddle solved! Despite its simple formula, the structure of the (SCN)(x)
      polymer has remained elusive since its first synthesis in 1929. From energetics
      as well as NMR chemical shifts, based on DFT calculations, we have strong
      evidence that it is indeed a tangle of linear chains, made up from N-linked
      S(2)C(2)N five-membered rings.Molecular fragments and crystal structures based on
      proposed structures for polythiocyanogen were studied by using molecular and
      solid-state electronic structure calculations at the density functional theory
      level. The energetics and chemical shifts from both types of calculations
      indicate that a planar N-linked chain consisting of 1,2,4-dithiazole five
      membered rings with adjacent rings pointing in opposite directions is the most
      likely local structure of the (SCN)(x) polymer.

PMID- 19177477
TI  - Furazan-functionalized tetrazolate-based salts: a new family of insensitive
      energetic materials.
AB  - Insensitive energetic salts: A series of furazan-functionalized tetrazolate-based
      energetic salts (see figure) were synthesized and characterized. All of the salts
      exhibit excellent thermal stabilities and high positive heats of
      formation.Furazan-functionalized tetrazolate-based energetic salts (1-13) were
      prepared by direct treatment of neutral 4-amino-3-(5-tetrazole)furazan and a
      Lewis base or by simple metathesis reactions of its barium salt formed in situ
      with the corresponding sulfate salts in aqueous solution. Key physical
      properties, such as melting point, thermal stability, density, hypergolicity, and
      sensitivity to shock, were measured. The relationship between their structures
      and these properties was determined. Most of salts exhibit better thermal
      stability than their 5-nitrotetrazolate and 5-nitraminotetrazolate analogues as
      well as other furazan-based salts. The structures of representative
      aminoguanidinium (4), carbonic hydrazylhydrazidinium (9), and 1,4-dimethyl-5
      aminotetrazolium salts (13) were further confirmed by single-crystal X-ray
      analysis. Their densities, heats of formation, detonation pressures and
      velocities, and specific impulses were calculated. All of the salts possess high
      positive heats of formation. The effect of the furazan ring on these
      physicochemical properties was examined and discussed.

PMID- 19177478
TI  - Enantioselective Friedel-Crafts alkylation of indoles with alkylidene malonates
      catalyzed by N,N'-dioxide-scandium(III) complexes: asymmetric synthesis of beta
      carbolines.
AB  - An efficient catalytic asymmetric Friedel-Crafts alkylation of indoles with
      alkylidene malonates has been developed by using a chiral N,N'-dioxide-Sc(OTf)(3)
      complex as the catalyst (see scheme). Some optically active intermediates
      containing the indole skeleton have been synthesized, such as indolepropionic
      acid, tryptamines, and beta-carbolines. The coordination between the scandium
      atom and the chiral N,N'-dioxide compound has been revealed by X-ray structure
      analysis.

PMID- 19177479
TI  - Organocatalytic domino Michael-Knoevenagel condensation reaction for the
      synthesis of optically active 3-diethoxyphosphoryl-2-oxocyclohex-3
      enecarboxylates.
AB  - Versatile dominoes: A novel, organocatalytic, Michael-Knoevenagel condensation
      domino reaction of ethyl 4-diethoxyphosphoryl-3-oxobutanoate with various aryl-
      and aliphatic-substituted alpha,beta-unsaturated aldehydes catalyzed by a chiral
      diarylprolinol ether has been successfully performed. The reaction proceeds in a
      highly enantio- and diastereoselective manner giving access to optically active 6
      substituted-3-diethoxyphosphoryl-2-oxocyclohex-3-enecarboxylates (see scheme).A
      novel, organocatalytic, highly enantio- and diastereoselective synthetic approach
      towards optically active 6-substituted-3-diethoxyphosphoryl-2-oxocyclohex-3
      enecarboxylates is presented. Our methodology utilizes a Michael-Knoevenagel
      domino reaction sequence of ethyl 4-diethoxyphosphoryl-3-oxobutanoate and
      alpha,beta-unsaturated aldehydes catalyzed by a chiral diarylprolinol ether. The
      cyclohexenecarboxylates obtained are particularly well suited for the preparation
      of highly functionalized cyclohexene and cyclohexane derivatives, with up to four
      chiral centers and high levels of stereocontrol.

PMID- 19177481
TI  - Iron-catalyzed ligand-free three-component coupling reactions of aldehydes,
      terminal alkynes, and amines.
AB  - A tri-umph in many respects: The iron-catalyzed ligand-free, one-pot three
      component coupling reactions of aldehydes, terminal alkynes, and amines in the
      presence of 4 A molecular sieves yields the corresponding propargylamines in good
      to excellent yields, displays a broad substrate scope, and is economical and
      environmentally friendly (see scheme).

PMID- 19177480
TI  - Iridium-catalyzed asymmetric hydrogenation of unfunctionalized enamines.
AB  - Optically active tertiary amines are readily prepared by iridium-catalyzed
      asymmetric hydrogenation of unfunctionalized enamines (see scheme). The best
      enantioselectivities with >90% ee were obtained with N-aryl- and N-benzyl
      substituted enamines with a terminal double bond. The hydrogenation of enamines
      derived from cyclic ketones, which has not been reported yet with other
      catalysts, gave enantiomeric excesses of up to 87%.

PMID- 19177482
TI  - Quadrupolar chromophores for voltage sensing and white-light generation.
AB  - A few-state model predicts that spectral properties of some quadrupolar
      chromophores are affected by the application of static electric fields. These
      dyes can monitor neuronal activity (action potential), as a sensitive and
      versatile alternative to classical dipolar dyes and can also be used in organic
      LEDs: color-tunable and/or white-light emission is obtained by varying the
      working voltage (see chromaticity diagram).

PMID- 19177483
TI  - Single-molecule fluorescence studies reveal long-range electron-transfer dynamics
      through double-stranded DNA.
AB  - Complex dynamics of combined long-range fluorescence resonance energy transfer
      (FRET) and short-range electron transfer (ET) processes in a single double
      stranded DNA (dsDNA) molecule (see figure) reveals that FRET remains almost
      unaltered in the presence of ET. Present systems also demonstrate the potential
      for long-range ET studies through the base stack in single dsDNA molecules.

PMID- 19177484
TI  - On the mechanism of floating and sliding of liquid marbles.
AB  - The mechanisms of floating and sliding of liquid marbles are studied. Liquid
      marbles containing CaCl(2) and marbles containing NaOH water solutions float on
      water containing Na(2)CO(3) and an alcoholic solution of phenolphthalein with no
      chemical reaction. Sliding of liquid marbles, consisting of NaOH water solutions,
      on polymer substrates coated with phenolphthalein is studied as well. No chemical
      reaction is observed. These observations supply direct experimental evidence for
      the suggestion that interfaces are separated by an air layer when marbles roll on
      solid substrates. It is concluded that a liquid marble rests on hydrophobic
      particles coating the liquid. In contrast, drops containing an NaOH water
      solution sliding on superhydrophobic surfaces coated with phenolphthalein leave a
      colored trace. The mechanism of low-friction sliding of drops deposited on
      superhydrophobic surfaces and liquid marbles turns out to be quite different:
      there is no direct contact between liquid and solid in the case of marbles'
      motion.

PMID- 19177485
TI  - Prognostic model to predict outcomes in nonsmall cell lung cancer patients
      treated with gefitinib as a salvage treatment.
AB  - BACKGROUND: A prognostic model based on clinical parameters for nonsmall cell
      lung cancer (NSCLC) patients treated with gefitinib (250 mg/day) as a salvage
      therapy was devised. METHODS: Clinical data regarding a total of 316 metastatic
      or recurrent NSCLC patients who were treated with gefitinib were analyzed.
      RESULTS: Poor prognostic factors for overall survival (OS) by multivariate
      analysis were an Eastern Cooperative Oncology Group (ECOG) performance status of
      2 to 3 (hazards ratio [HR] of 2.07; 95% confidence interval [CI], 1.57-2.73 [P <
      .001]), the presence of intra-abdominal metastasis (HR of 1.76; 95% CI, 1.33-2.34
      [P < .001]), elevated serum alkaline phosphatase (HR of 1.50; 95% CI, 1.13-2.00
      [P = .005]), time interval from diagnosis to gefitinib therapy of < or =12 months
      (HR of 1.48; 95% CI, 1.12-1.95 [P = .005]), low serum albumin (HR of 1.45; 95%
      CI, 1.09-1.92 [P = .009]), progression-free interval for previous chemotherapy of
      < or =12 weeks (HR of 1.40; 95% CI, 1.0-1.84 [P = .015]), white blood cell >
      10,000/microL (HR of 1.38; 95% CI, 1.02-1.85 [P = .032]), and ever-smoker (HR of
      1.33; 95% CI, 1.02-1.75 [P = .033]). Of the 272 patients applicable to this
      prognostic model, 41 patients (15%) were categorized as a good prognosis group (0
      1 risk factors), 100 patients (37%) as an intermediate prognosis group (2-3 risk
      factors), 81 patients (30%) as a poor prognosis group (4-5 risk factors), and 50
      patients (16%) as a very poor prognosis group (> or = 6 risk factors). The median
      OS from the time of gefitinib treatment for the good, intermediate, poor, and
      very poor prognosis groups were 18.0 months, 11.2 months, 4.0 months, and 1.3
      months, respectively (P < .001). CONCLUSIONS: This prognostic model based on
      easily available clinical variables would be useful to identify patients who
      might derive more benefit from gefitinib treatment and to make decisions in
      clinical practice.

PMID- 19177486
TI  - Interstitial deletion of 11q in a mother and fetus: implications of directly
      transmitted chromosomal imbalances for prenatal genetic counseling.

PMID- 19177487
TI  - The transporter "variome": the missing link between gene variants and bile salt
      transporter function.

PMID- 19177488
TI  - The "health" and future of the physician-scientist in hepatology.

PMID- 19177489
TI  - A new section: image of the month.

PMID- 19177490
TI  - Test of the role of nicotine dependence in the relation between posttraumatic
      stress disorder and panic spectrum problems.
AB  - Posttraumatic stress disorder (PTSD) frequently co-occurs with panic spectrum
      problems. Relatively little empirical work has tested possible mechanisms
      accounting for this association. Nicotine dependence often ensues subsequent to
      PTSD onset and research suggests smoking high numbers of cigarettes daily may
      lead to panic problems. The current study tested the hypotheses that nicotine
      dependence partially mediates the relations between PTSD and both panic attacks
      and panic disorder within a nationally representative sample of 5,692 (3,020
      women; M(Age) = 45, SD = 18) adults from the National Comorbidity Survey
      Replication. Results were consistent with hypotheses. These findings support the
      theory suggesting smoking among people with PTSD may be involved in the
      development of panic problems.

PMID- 19177491
TI  - Sexual harassment in the Marines, posttraumatic stress symptoms, and perceived
      health: evidence for sex differences.
AB  - Sex differences and pretrauma functioning have been understudied in examinations
      of posttraumatic stress symptoms (PSS) and health. This study examined
      relationships between sexual harassment and assault in the military (MST), PSS,
      and perceived physical health when accounting for pre-MST PSS, pre-MST health,
      and current depression. Relationships were examined separately in 226 female and
      91 male Marines endorsing recent MST (past 6 months). MST predicted increased PSS
      for women and especially men. For men, higher levels of MST were associated with
      worse perceived physical health, whereas for women, lower levels of MST were
      associated with worse perceived health. For men with MST, there was some evidence
      for the association being partially mediated by PSS, but no mediation was found
      in women.

PMID- 19177492
TI  - Changing of the guard.

PMID- 19177493
TI  - Design and evaluation of thin and flexible theophylline imprinted polymer
      membrane materials.
AB  - The aim of this work was to produce a thin, flexible and diffusion able
      molecularly imprinted polymeric matrix with good template accessibility.
      Membranes were prepared using a non-covalent molecular imprinting approach and
      their physical characteristics and binding capabilities investigated. Two
      materials were used, a poly(tri-ethyleneglycol dimethyacrylate-co-methyl
      methacrylate-co-methacrylic acid) copolymer containing 14% cross-linker and a
      monomer (g) to porogen (ml) ratio of 1:0.5 (A), and a blend of poly(TEGMA-co-MAA)
      and polyurethane (B). The polyurethane was added to improve membrane flexiblity
      and stability. The polymers were characterized using AFM, SEM and nitrogen
      adsorption, whilst binding was evaluated using batch-rebinding studies. For all
      membranes the specific surface area was low (<10 m(2)/g). MIP (A) films were
      shown to bind specifically at low concentrations but specific binding was masked
      by non-specific interactions at elevated concentrations. Selectivity studies
      confirmed specificity at low concentrations. K(D) approximations confirmed a
      difference in the population of binding sites within NIP and MIP films. The data
      also indicated that at low concentrations the ligand-occupied binding site
      population approached homogeneity. Scanning electron microscopy images of
      membrane (B) revealed a complex multi-layered system, however these membranes did
      not demonstrate specificity for the template. The results described here
      demonstrate how the fundamental parameters of a non-covalent molecularly
      imprinted system can be successfully modified in order to generate flexible and
      physically tolerant molecularly imprinted thin films.

PMID- 19177494
TI  - Epitope mapping of a chimeric CD137 mAb: a necessary step for assessing the
      biologic relevance of non-human primate models.
AB  - Antibody based manipulation of the CD137 (4-1BB) co-signaling pathway is an
      attractive option for the treatment of cancer and autoimmune disease. We
      developed a chimeric anti-human CD137 monoclonal antibody (GG) and characterized
      its function. As a component of planned preclinical studies, we evaluated the
      binding of GG to activated peripheral blood mononuclear cells (PBMCs) from
      cynomolgus macaque and baboon against human. Interestingly, GG only recognized
      human CD137, while a commercial anti-CD137 mAb (4B4-1), recognized activated
      PBMCs from both human and non-human primates (NHP). Subsequent analysis revealed
      that the amino acid sequence of CD137 is largely conserved between primate
      species ( approximately 95% identical), with the extracellular domain differing
      by only 9-10 amino acids. Based on these data, we generated mutant constructs in
      the extracellular domain, replacing NHP with human CD137 sequences, and
      identified 3 amino acids critical for GG binding. These residues are likely part
      of a conformational epitope, as a peptide spanning this region is unable to block
      mAb binding. These data demonstrate that subtle sequence variations of defined co
      stimulatory molecules amongst primate species can be employed as a strategy for
      mapping residues necessary for antibody binding to conformational epitopes.

PMID- 19177495
TI  - Screening HIV-1 antigenic peptides as receptors for antibodies and CD4 in
      allosteric nanosensors.
AB  - We have analyzed the suitability of six antigenic peptides from several HIV-1
      structural proteins (namely gp41, gp120, p17, and p24), as anti-HIV-1 antibody
      receptors in an allosteric enzymatic biosensor. These peptides were inserted in a
      solvent-exposed surface of Escherichia coli (E. coli) beta-galactosidase by means
      of conventional recombinant DNA technology. The resulting enzymes were tested to
      allosterically respond to sera from HIV-1-infected individuals. Only stretches
      from gp41 and gp120 envelope proteins were able to transduce the molecular
      contact signal in the presence of immunoreactive sera. Intriguingly, the enzyme
      displaying the CD4 binding site segment KQFINMWQEVGKAMYAPP was activated by
      soluble CD4, suggesting that it produces conformational modifications on the
      allosteric enzyme as those occurring during antibody-promoted induced fit. This
      fact is discussed in the context of the design of smart protein drugs and markers
      targeted to CD4+ cells.

PMID- 19177496
TI  - Psychometric attributes of the Hospital Anxiety and Depression Scale in
      Parkinson's disease.
AB  - The Hospital Anxiety and Depression Scale (HADS) has been used in Parkinson's
      disease (PD) but information about its psychometric properties in this context is
      limited. The aim of this study is to assess the psychometric properties of the
      HADS in PD. In an observational, cross-sectional analysis, HADS data quality,
      acceptability, scaling assumptions, internal consistency, construct validity, and
      precision were explored. From a sample of 387 PD patients, 22% and 14% scored >
      or =11 points (definite case) on the HADS anxiety and depression subscales,
      respectively. Cronbach's alpha was 0.81 and 0.83 for these subscales. Factor
      analysis revealed two factors (49.8% of the variance) representing anxiety and
      depression. The HADS closely correlated with health-related quality of life
      (HRQL) measures and displayed satisfactory discriminative validity for patients
      grouped by severity level, disease duration, HRQL status, and treatment. The SEM
      was 1.84 for HADS-Anxiety and 1.72 for HADS-Depression. The HADS is an
      acceptable, consistent, valid, precise, and potentially responsive scale for use
      in PD.

PMID- 19177497
TI  - Epithelial inclusion cyst arising in an intramammary lymph node: case report with
      cytologic findings.
AB  - The occurrence of epithelial inclusion cysts (EIC) in axillary lymph nodes is a
      rare but well recognized entity, arising either from direct implantation or from
      embryonal rests. Theoretically, EIC can occur in intramammary lymph nodes, but
      there has been only one prior report of such a lesion. Here, we describe a case
      of an EIC arising in an intramammary lymph node of a 37-year-old woman. This
      report focuses on the FNA cytologic features of this lesion and its differential
      diagnoses. On FNA, the EIC arising in an intramammary lymph node was
      characterized by mature lymphocytes, squamous epithelial cells, and keratinizing
      material. The presence of squamous cells can lead to the erroneous diagnosis of
      more common breast lesions, such as squamous cell carcinoma or metaplastic
      carcinoma. Contrary to these more sinister diagnoses, EIC arising in an
      intramammary lymph node is a benign condition. As this rare lesion sometimes
      mimics a neoplasm both clinically and radiographically, awareness of this entity
      is important to prevent over treatment.

PMID- 19177498
TI  - In vitro genotoxic assessment of xenobiotic diacylglycerols in an in vitro
      micronucleus assay.
AB  - Xenobiotic diacylglycerols (DG) may induce pathological disorders by causing
      abnormal chromosomal segregation, which could be aneuploid. In this study, seven
      xenobiotic-diacylglycerols (four of drug origin and three of pesticide origin)
      were evaluated for their ability to induce aneuploidy in mammalian cultures using
      in vitro cytokinesis blocked micronucleus (CBMN) assay coupled with kinetochore
      labeling and interphase fluorescent in situ hybridization. Out of seven xeno-DGs,
      two (ibuprofen-DG and fenbufen-DG) induced statistically significant (P < 0.001)
      and dose-dependent increase in micronucleus induction, but this apparent
      micronucleus induction was very weak in case of fenbufen-DG. These MN were
      produced predominantly by aneugenic and clastogenic mechanisms, respectively,
      confirmed by immunofluorescent labeling of kinetochores. Fluorescent in situ
      hybridization analysis revealed that ibuprofen-DG induced significantly higher
      nondisjunction for chromosomes 10, 17, and 18. Other xenobiotic diacylglycerols
      (indomethacin-DG, salicylic acid-DG, 4-(2-methyl-4-chlorophenoxy) butanoic acid
      DG (MCPB-DG), 2-(2-methyl-4-chlorophenoxy) propanoic acid-DG (MCPP-DG) and 2-(4
      dichlorophenoxy)-butanoic acid-DG (2,4 DB-DG) did not induce micronuclei, but the
      concentrations tested did not reach levels that caused the marked growth
      suppression typically required for testing for regulatory testing purposes.
      However, the levels of growth suppression achieved were similar to that seen with
      ibuprofen-DG, which was positive. This study shows that xeno-DGs, which have been
      neglected in the past for their possible link to any pathological disorders, need
      serious assessment of their mutagenic potential.

PMID- 19177499
TI  - MTBITC mediates cell cycle arrest and apoptosis induction in human HepG2 cells
      despite its rapid degradation kinetics in the in vitro model.
AB  - Despite the great variety of structure homologous, experimental research on the
      cancer preventive properties of isothiocyanates (ITCs) is limited to only a
      fractional amount thereof so far. Especially the degradation of these compounds
      in the experimental system has not been investigated so far. In this study, we
      investigated the effect of 4-methylthiobutyl isothiocyante (MTBITC) on the
      proliferation of human hepatoma (HepG2) cells and underlying mechanisms. A
      concentration and time-dependent reduction in proliferation activity could be
      observed in cells treated with MTBITC exceeding 10 microM. At these
      concentrations MTBITC-induced apoptosis in HepG2 cells could be observed by
      internucleosomal DNA fragmentation, flow cytometry analysis, and the detection of
      single-stranded apoptotic DNA. In all the three assays, clear apoptotic events
      were present after 6-hr exposure to MTBITC. Apoptosis induction was accompanied
      by a time-dependent arrest of HepG2 cells at the G2/M phase of the cell cycle.
      This study shows for the first time the inhibitory potency of MTBITC on
      metabolically competent hepatoma cells, whereas the loss of reduced glutathione
      and its impact on mitochondria seem to be the major processes involved in the
      initiation and execution of the apoptotic cell death. The results of this study
      also showed that irrespective of the intense degradation kinetics of MTBITC, the
      strong cytostatic effect of the ITC was not markedly affected by it and suggests
      that although ITCs are only present at maximum concentrations in a living system
      for a rather short time, this might be sufficient to exert their therapeutic
      effects.

PMID- 19177500
TI  - DNA damage in peripheral blood leukocytes of physically active individuals as
      measured by the alkaline single cell gel electrophoresis assay.
AB  - DNA damage induced by physical activity and/or exercise has been reported under
      different conditions but not for individuals maintaining physical fitness by
      regular strenuous exercise. Therefore, we compared levels of DNA damage in blood
      leukocytes of 40 healthy individuals (35 males, 5 females) who regularly
      exercised in gymnasiums/health clubs and 15 healthy sedentary controls who had
      never exercised. The former group was selected (after informed consent) on the
      basis of how long they had been exercising on a regular basis as well as their
      exercise schedule and regimen. The length of time since starting a regular
      exercise regimen ranged from 2 months to 9 years, whereas the daily exercise
      duration ranged from 40 min to 3 hrs and warm-up sessions ranged from none to 90
      min. The length of DNA migration (44.66 +/- 2.68 microm in males, 29.62 +/- 1.69
      microm in females) and the percentage of cells with tails (79.86 +/-1.27% in
      males, 67.20 +/- 0.96% in females) in peripheral blood leukocytes of physically
      active individuals were increased significantly (P < 0.001) with respect to
      corresponding values in control males and females (18.85 +/- 1.79 microm, 23.37
      +/- 3.94 microm; 24.50 +/- 1.98%, 33.00 +/- 4.44%, respectively). Highly
      significant differences for DNA damage were also observed between physically
      active males and females. These observations, in the absence of any other
      exposures, indicate a correlation between strenuous exercise to keep fit and
      increased levels of DNA damage. This finding may have relevance in terms of the
      ageing process, with diseases associated with aging, and with carcinogenesis.

PMID- 19177501
TI  - Chromosomal aberrations in railroad transit workers: effect of genetic
      polymorphisms.
AB  - Complex chemical mixtures are transported by train from Russia to Finland for
      further shipment. Here, we studied if exposure to genotoxic components among
      these substances could affect chromosomal aberrations (CAs) in peripheral
      lymphocytes of workers handling the tank cars. An initial survey among 48
      railroad workers and 39 referents (male smokers and nonsmokers) showed an
      elevation of CAs. A campaign was started to reduce exposures through preventive
      measures. Five years later, 51 tank car workers and 40 age-matched referents (all
      nonsmoking men) were studied for CAs and genetic polymorphisms of xenobiotic
      metabolism (EPHX1, GSTM1, GSTP1, GSTT1, NAT1, NAT2), DNA repair (ERCC2, ERCC5,
      XPA, XPC, XRCC1, XRCC3), and folate metabolism (MTHFR, MTR). No increase in CAs
      was seen in the exposed group, suggesting that the preventive measures had been
      successful. However, a positive association existed between exposure duration and
      CA level among the exposed subjects. The level of chromosome-type breaks was
      actually lower in the exposed workers than the referents, particularly among
      MTHFR wild-type homozygotes or XRCC3 codon 241 variant allele carriers,
      suggesting modulation of CA frequency by folate metabolism and DNA repair. An
      interaction was observed between the occupational exposure and MTHFR, EPHX1, and
      MTR genotypes in determining CA level. The NAT2, ERCC2 exon 10, and XRCC1 codon
      194 polymorphisms also affected CA frequency. Our findings suggest that handling
      of tank cars containing complex chemical mixtures poses a genotoxic risk, which
      may be reduced by preventive measures. Several genetic polymorphisms seem to
      modify the genotoxic effect or baseline CA level.

PMID- 19177502
TI  - Surface cleaning of germanium nanodot ionization substrate for surface-assisted
      laser desorption/ionization mass spectrometry.
AB  - In surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS), a
      chemical background signal, arising from organic contaminants such as
      plasticizers, is frequently observed mainly under m/z ca. 600, which impairs the
      advantages of the matrix-free approach. Silver salts, which are used for the
      cationization of aromatic compounds, are also difficult to remove completely
      after the measurements. In this study, surface cleaning techniques used in
      semiconductor processing were used to clean our developed silicon-based SALDI
      substrate on which self-assembled germanium nanodots (GeNDs) had been deposited
      (termed a GeND chip). An immersion cleaning method using acetone with sonication,
      and a sulfuric-peroxide mixture (SPM) cleaning method using a mixture of
      H(2)SO(4)/H(2)O(2)/deionized water, were examined for their effectiveness in
      removing organic compounds and residual silver salts. Removal of both types of
      contaminants was successfully performed by SPM cleaning. The limit of detection
      for glutathione was improved from ca. 5 pmol without cleaning to ca. 50 fmol
      after the SPM cleaning. Since GeND chips can tolerate acidic cleaning and
      sonication due to their chemical inertness and rigid nanodot structures, they
      appear to be an ideal reusable SALDI substrate.

PMID- 19177503
TI  - Imaging organic and mineral phases in a biomineral using novel contrast
      techniques.
AB  - Chitons are marine molluscs that mineralize their teeth by the process of matrix
      mediated biomineralization. The teeth develop in a continuous manner forming hard
      minerals, including magnetite, making analysis of the matrix within these
      mineralized regions difficult. This article describes the use of charge contrast
      imaging techniques, rarely applied to biological samples, to simultaneously image
      the organic and mineral phases within the teeth of these animals. Resulting
      evidence demonstrates the power of this technique in delivering architectural
      information concerning both the matrix and mineral phases, without the need for
      removal of the hard mineralized material.

PMID- 19177504
TI  - Effects of long-acting beta adrenergic agonists on vocal fold ion transport.
AB  - OBJECTIVES: Inhaled medications prescribed for the hypersensitive airway
      typically combine corticosteroids and long-acting beta2 adrenergic agonists
      (LABAs). The phonatory side effects of these combination treatments are widely
      recognized. However, there is limited understanding of the physiological changes
      induced by these medications that underlie the phonatory side effects. The
      objective of this study was to investigate the distinct effects of
      corticosteroids and LABAs on vocal fold mucosal physiology. Understanding the
      physiological changes to the vocal folds after corticosteroid and LABA treatments
      is necessary to prevent the prevalent vocal decrement associated with these
      medications. STUDY DESIGN: Experimental in vitro design with treatment and
      control groups. METHODS: Native porcine vocal fold mucosae (N = 38) were exposed
      to corticosteroid or LABA treatments. Ion transport was measured continuously at
      baseline and after treatment. To quantify the nature of ion transport, vocal
      folds were also treated with chloride and sodium channel inhibitors. RESULTS:
      Corticosteroid treatment did not alter ion transport. Conversely, exposure to
      LABAs significantly increased ion transport. This increase in ion transport was
      transient, observed immediately after treatment in all tissue and associated with
      increased chloride secretion. CONCLUSIONS: The distinct effects of
      corticosteroids and LABAs on vocal fold physiology have not been examined to
      date. This study demonstrates that short-term treatment with LABAs, but not
      corticosteroids, significantly increases ion transport. These findings suggest
      that one underlying physiological mechanism for phonatory changes associated with
      inhaled treatments may be related to acute alterations in vocal fold ion
      transport and surface hydration.

PMID- 19177505
TI  - Fragmentation pathways of some benzothiophene radical cations formed by
      atmospheric pressure chemical ionisation.
AB  - Polycyclic aromatic sulfur-containing compounds (PASHs) are commonly found in
      fossil fuels and are of considerable importance in environmental studies. This
      work presents detailed studies on the fragmentation patterns of radical cations
      formed from four representative PASHs, benzo[b]thiophene, dibenzothiophene, 4
      methyldibenzothiophene and 4,6-dimethyldibenzothiophene, using tandem atmospheric
      pressure chemical ionization mass spectrometry (APCI-MS/MS). Understanding these
      fragmentation patterns can be a useful aid in the analysis of PASHs employing
      APCI or electron ionization (EI-MS/MS), either alone or in conjunction with
      liquid or gas chromatography.

PMID- 19177506
TI  - A liquid chromatography/tandem mass spectrometry method for detecting UGT
      mediated bioactivation of drugs as their N-acetylcysteine adducts in human liver
      microsomes.
AB  - The detection of the reactive metabolites of drugs has recently been gaining
      increasing importance. In vitro trapping studies using trapping agents such as
      glutathione are usually conducted for the detection of reactive metabolites,
      especially those of cytochrome P450-mediated metabolism. In order to detect the
      UDP-glucuronosyltransferase (UGT)-mediated bioactivation of drugs, an in vitro
      trapping method using N-acetylcysteine (NAC) as a trapping agent followed by
      liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed in this
      study. After the test compounds (diclofenac and ketoprofen) had been incubated in
      human liver microsomes with uridine diphosphoglucuronic acid (UDPGA) and NAC, the
      NAC adducts formed through their acyl glucuronides were analyzed using LC/MS/MS
      with electrospray ionization (ESI). The NAC adduct showed a mass shift of 145
      units as compared to its parent, and the characteristic ion fragmentations
      reflected the parent. This is a concise and high-throughput method for evaluating
      reactive metabolites by UGT-mediated bioactivation.

PMID- 19177507
TI  - FemtoMolar measurements using accelerator mass spectrometry.
AB  - Accelerator mass spectrometry (AMS) is an ultra-sensitive analytical method
      suitable for the detection of sub-nM concentrations of labeled biological
      substances such as pharmaceutical drugs in body fluids. A limiting factor in
      extending the concentration measurements to the sub-pM range is the natural (14)C
      content in living tissues. This was circumvented by separating the labeled drug
      from the tissue matrix, using standard high-performance liquid chromatography
      (HPLC) procedures. As the separated total drug amount is in the few fg range, it
      is not possible to use a standard AMS sample preparation method, where mg sizes
      are required. We have utilized a sensitive carbon carrier method where a (14)C
      deficient compound is added to the HPLC fractions and the composite sample is
      prepared and analyzed by AMS. Using 50 microL human blood plasma aliquots, we
      have demonstrated concentration measurements below 20 fM, containing sub-amol
      amounts of the labeled drug. The method has the immediate potential of operating
      in the sub-fM region.

PMID- 19177508
TI  - Pulsed radiofrequency glow discharge time-of-flight mass spectrometry for
      molecular depth profiling of polymer-based films.
AB  - We demonstrate the potential of an innovative technique, pulsed radiofrequency
      glow discharge time-of-flight mass spectrometry, for the molecular depth
      profiling of polymer materials. The technique benefits from the presence, in the
      afterglow of the pulsed glow discharge, of fragment ions that can be related to
      the structures of the polymers under study. Thin films of different polymers
      (PMMA, PET, PAMS, PS) were successfully profiled with retention of molecular
      information along the profile. Multilayered structures of the above polymers were
      also profiled, and it was possible to discriminate among layers having similar
      elemental composition but different polymer structure.

PMID- 19177509
TI  - Patient trust-in-physician and race are predictors of adherence to medical
      management in inflammatory bowel disease.
AB  - BACKGROUND: Adherence plays an important role in the therapeutic effectiveness of
      medical therapy in inflammatory bowel disease (IBD). We assessed whether trust-in
      physician and Black race were predictors of adherence. METHODS: We performed a
      cross-sectional study of Black (n = 120) and White (n = 115) IBD patients
      recruited from an outpatient IBD clinic. Self-reported adherence to taking
      medication and keeping appointments, trust-in-physician, and health-related
      quality of life were measured using the validated instruments, the modified Hill
      Bone Compliance Scale (HBCS), the Trust-in-Physician Scale (TIPS), and the Short
      IBD Questionnaire (SIBDQ), respectively. RESULTS: Overall adherence was 65%.
      Higher adherence correlated with greater trust-in-physician (r = -0.30; P <
      0.0001), increasing age (r = -0.19; P = 0.01), and worsening health-related
      quality of life (r = -0.18; P = 0.01). Adherence was also higher among White IBD
      patients compared to Blacks (HBSC: 15.6 versus 14.0, P < 0.0001). Trust-in
      physician, race, and age remained predictors of adherence to medical management
      after adjustment for employment, income, health insurance, marital and
      socioeconomic status, and immunomodulator therapy. The adjusted odds ratio for
      adherence in Blacks compared to Whites was 0.29 (95% confidence interval: 0.13
      0.64). Every half standard deviation increase in trust-in-physician and every
      incremental decade in age were associated with 36% and 47% higher likelihood of
      adherence, respectively. CONCLUSIONS: Trust-in-physician is a potentially
      modifiable predictor of adherence to IBD medical therapy. Black IBD patients
      exhibited lower adherence compared to their White counterparts. Understanding the
      mechanisms of these racial differences may lead to better optimization of
      therapeutic effectiveness.

PMID- 19177510
TI  - Long-term changes in dopamine-stimulated gene expression after single-day
      methamphetamine exposure.
AB  - Methamphetamine (mAMPH) is a highly addictive psychostimulant drug that injures
      monoaminergic neurons and results in behavioral impairments in humans and
      animals. Although evidence exists for changes in cortical volume, metabolism, and
      blood oxygenation levels in human mAMPH abusers, animal models have instead
      emphasized this drug's long-lasting influence on ascending monoaminergic
      (dopamine, serotonin) projections. The aim of this study was to investigate
      cortical and subcortical function in rats long after administration of a single
      day mAMPH regimen known to damage monoaminergic systems, at a time point when
      behavioral impairments are still evident. Rats were given either saline or a
      neurotoxic (4 x 4 mg/kg, sc) mAMPH regimen. Five weeks later, they were given
      pharmacological treatments that stimulate cortical gene expression: either the
      dopaminergic agonist apomorphine (3 mg/kg, sc) or the muscarinic acetylcholine
      agonist pilocarpine (25 mg/kg, ip). Cortical and subcortical immediate early gene
      (IEG) responses were measured by immunocytochemical analysis of Fos or JunB,
      protein products of the IEGs, c-fos and junB. Compared with saline-pretreated
      controls, mAMPH-pretreated animals had about 50-70% fewer Fos- and JunB
      immunoreactive cells in anterior cingulate, infralimbic, orbital, somatosensory,
      and rhinal cortices as well as caudate-putamen and nucleus accumbens, 90 min
      after apomorphine challenge. By contrast, mAMPH-pretreated rats had no reductions
      in the numbers of Fos or JunB-positive cells following pilocarpine challenge.
      This study demonstrates the profound and enduring effects of mAMPH administration
      on dopamine-stimulated cortical function in animals.

PMID- 19177511
TI  - Asenapine exerts distinctive regional effects on ionotropic glutamate receptor
      subtypes in rat brain.
AB  - Asenapine, a new pyschopharmacologic agent being developed for the treatment of
      schizophrenia and bipolar disorder, has a unique human receptor binding signature
      with strong affinity for dopaminergic, alpha-adrenergic, and, in particular,
      serotonergic receptors raising the possibility of interactions with glutamatergic
      receptors. Changes in ionotropic glutamate (Glu) N-methyl-D-aspartic acid (NMDA)
      receptors and 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA)
      receptors in rat forebrain regions were quantified after repeated administration
      of multiple doses of asenapine (0.03, 0.1, or 0.3 mg/kg, subcutaneous, twice/day)
      or vehicle for 4 weeks. Brain sections were collected from the medial prefrontal
      cortex (mPFC), dorsolateral frontal cortex, caudate putamen (CPu), nucleus
      accumbens (NAc), and hippocampus (HIP), and processed for in vitro receptor
      autoradiography. Four weeks of treatment with 0.03, 0.1, or 0.3 mg/kg of
      asenapine significantly (P < 0.01) decreased binding of [3H]MK-801 to NMDA/MK-801
      modulatory sites in NAc (by 27%, 29%, and 26%, respectively), medial CPu (by 25%,
      28%, and 24%), and lateral CPu (by 24%, 31%, and 26%). In contrast, the same
      doses of asenapine did not alter binding of [3H]glycine to NMDA/glycine
      modulatory sites in any of the brain regions examined. [3H]AMPA binding to AMPA
      receptors was selectively and significantly (P < 0.001) elevated in hippocampal
      CA(1) (41%) and CA(3) (40%) regions but only at the highest dose tested. These
      results indicate that chronic treatment with asenapine has region-specific and
      dose-dependent effects on ionotropic Glu-receptor subtypes in rat forebrain,
      which might contribute to the unique psychopharmacologic properties of asenapine.

PMID- 19177512
TI  - Magnetosensory function in rats: localization using positron emission tomography.
AB  - The aim of this study was to show that low-strength electromagnetic fields (EMFs)
      produced evoked potentials in rats and to localize the activated region in the
      brain. In response to a 2.5-G, 60-Hz stimulus, onset- and offset-evoked
      potentials were detected (P < 0.05 in each of the 10 animals studied); the evoked
      potentials had the same magnitude, latency, and nonlinear relationship to the
      field seen in previous studies on rabbits and human subjects. The neuroanatomical
      region of activation associated with the electrophysiological effect was
      identified by positron emission tomography using fluorodeoxyglucose. Paired
      emission scans (the same animal with and without field treatment) from 10
      additional rats were differenced and averaged to produce a t-statistic image
      using the pooled variance; the t value of each voxel was compared with a
      calculated critical t value to identify the activated voxels (P < 0.05). A brain
      volume of 13 mm(3) (15 voxels) located in the posterior, central cerebellum was
      found to have been activated by exposure to the field. Taken together, the
      results indicated that magnetosensory evoked potentials in the rats were
      associated with increased glucose utilization in the cerebellum, thereby
      supporting earlier evidence that EMF transduction occurred in the brain.

PMID- 19177514
TI  - Fed and fasted gastric pH and gastric residence time in conscious beagle dogs.
AB  - The gastric pH values are controversial in the literature. Some suggest the dog
      gastric pH is higher than human and dog gastric pH after fed with particular diet
      is uncertain. Gastric pH in 16 male beagle dogs was measured using Bravo pH
      telemetry system. For the fed study, the dogs received 10 or 200 g of dog dry
      food (5L18) 15 min before dosing the Bravo pH capsule, followed by a 50 mL of
      water to aid in swallowing. It was surprising to find a small, but statistically
      significantly lower pH in the fed compared to the fasted stomach. The average
      gastric pH in fasted dogs was 2.05 and 1.08 and 1.26 for 10 and 200 g fed dogs.
      The average gastric emptying time of the capsule was 1.4, 9.4 and 20 h for
      fasted, 10 g fed and 200 g fed dogs, respectively. The inter-individual
      variability was higher in fasted dogs than in fed dogs. The results showed the
      gastric pH in each colony of dogs can be different from reported values in the
      literature. It emphasizes that the importance of measuring the pH in each colony
      when dogs are used to evaluate pharmacokinetics of pH sensitive drugs or
      formulations.

PMID- 19177515
TI  - Pharmacokinetic allometric scaling of antibodies: application to the first-in
      human dose estimation.
AB  - The objectives of this study are: (i) to evaluate the predictive performance of
      interspecies scaling for antibodies to predict clearance, volume of distribution
      at steady state, and half-life in humans from animal data and (ii) to estimate
      first-in-human dose based on the predicted human clearance. Four methods were
      used to predict clearance in humans: (1) clearance versus body weight (simple
      allometry), (2) the product of clearance and maximum life-span potential (MLP)
      versus body weight, (3) the product of clearance and brain weight versus body
      weight, and (4) the application of a fixed exponent of 0.75. Based on the
      predicted human clearance, six methods were used to estimate the first-in-human
      dose. The predicted pharmacokinetic parameters and the estimated first-in-human
      dose of antibodies were compared with the observed human values. The results of
      the study indicated that the clearance of antibodies can be predicted with
      reasonable accuracy in humans and a good estimate of first human dose can be
      obtained from the predicted human clearance.

PMID- 19177516
TI  - Effect of formulation parameters and drug-polymer interactions on drug release
      from starch acetate matrix tablets.
AB  - The aim of this study was to determine, whether interactions between a drug and
      hydrophobic polymer matrix are present, and if so, how they affect the drug
      release. In addition, the most important formulation parameters, for example
      porosity or structure of the tablet, which have the greatest impact on drug
      release, were defined. Six different drug compounds, that is allopurinol,
      acyclovir, metronidazole, paracetamol, salicylamide and theophylline, were used
      in different formulations with hydrophobic starch acetate (DS 2.7) as a matrix
      forming polymer. Results indicate that the formulation parameters describing
      directly or indirectly the structure of the matrix, such as porosity, compaction
      force and the particle size fraction of the filler-binder, have the strongest
      impact on drug release. The contribution of drug property based variables is not
      as high as formulation parameters, but they cannot be overlooked. The
      contribution of water solubility and dissolution rate of the compound are
      obvious, but there are other significant parameters, which describe the
      hydrophobic and hydrophilic regions of the molecule, that also affect the drug
      release. This can be seen especially with the salicylamide: compound which
      appears to have a strong and sufficiently high hydrophobic region that interacts
      with starch acetate and impairs the drug release.

PMID- 19177517
TI  - Expression of somatostatin and neuropeptide Y in the embryonic, postnatal, and
      adult mouse amygdalar complex.
AB  - Recent developmental studies indicate that distinct neuronal subpopulations in
      the amygdala, including somatostatin (SOM)-containing neurons, originate from
      progenitor domains in the anterior entopeduncular area, thus suggesting a
      different origin from subpallial territories for amygdalar versus cortical SOM
      expressing interneurons, the latter derived from the dorsal part of the medial
      ganglionic eminence. In this context, we carried out an immunohistochemical study
      analyzing spatiotemporal expression patterns for SOM- and neuropeptide Y (NPY)
      containing neurons in the embryonic, postnatal, and adult mouse amygdala. Our
      results indicate that SOM- and NPY-immunoreactive cells are present in the
      amygdalar complex from embryonic day (E)12.5, and that these peptidergic cells
      seem to arise from the anterior entopeduncular area progenitor domain. From E12.5
      on there was a notable increase in the number and immunoreactivity of cells
      containing these peptides in distinct territories of the amygdalar complex,
      reaching a peak around birth. The distribution pattern for NPY neurons was very
      similar to that of SOM neurons in most nuclei of the amygdala, although the
      number of NPY neurons was always lower than that of SOM. At postnatal ages a
      reduction in the number of immunoreactive cells is observed in most amygdalar
      nuclei, remaining then similar from P14 to the adult. We interpret this reduction
      of the number of immunoreactive neurons in relation to the increased
      immunoreactivity for axons that occurs postnatally. We also suggest that the
      anterior entopeduncular area-derived SOM- and NPY-containing neurons in pallial
      and subpallial amygdaloid nuclei become local interneurons and projection
      neurons, respectively.

PMID- 19177518
TI  - Preferential localization of neural cell recognition molecule NB-2 in developing
      glutamatergic neurons in the rat auditory brainstem.
AB  - NB-2 is a neuronal cell recognition molecule that is preferentially expressed in
      auditory pathways. Mice deficient in the NB-2 gene exhibit aberrant responses to
      acoustic stimuli. Here we examined the expression and localization of NB-2 in the
      auditory brainstem during development in the rat. NB-2 was strongly expressed in
      the ventral cochlear nucleus (VCN), ventral acoustic stria, lateral and medial
      superior olivary complex (SOC), superior paraolivary nucleus, medial nucleus of
      the trapezoid body (MNTB), ventrolateral lemniscus, and central nucleus of the
      inferior colliculus (CIC). In the VCN and CIC, NB-2 was expressed in the regions
      that are known to respond to high frequencies. In situ hybridization combined
      with immunohistochemistry suggested that NB-2 is expressed only in neurons. NB-2
      was colocalized with glutamatergic elements in the neuropil and the calyces of
      Held but not with glycinergic or GABAergic elements. NB-2 expression in the SOC
      was first detected at embryonic day (E)19, reached a maximum level at postnatal
      day (P)7, and declined thereafter. Immunolabeling with VGLUT1 and VGLUT2, markers
      for mature and premature glutamatergic synapses, respectively, in combination
      with NB-2 immunolabeling revealed that NB-2 is expressed at glutamatergic
      synapses. Collectively, our findings suggest that NB-2 plays a key role in
      maturation of glutamatergic synapses in the brainstem during the final stages of
      auditory development.

PMID- 19177519
TI  - Regional differences in olfactory epithelial homeostasis in the adult mouse.
AB  - The olfactory sensory neurons in the nasal cavity of the adult mouse are
      organized into a few regions that differ in their molecular properties, as
      several classes of genes show regional expression. Most renowned is the fact that
      expression of each of hundreds of different odorant receptor genes is limited to
      one such region, or zone, of the olfactory neuroepithelial sheet. Zone
      differences are in place at birth, as exemplified here by the expression of
      neuronal progenitor marker Foxg1. We herein describe that an adult pattern
      showing regional differences in neurogenesis develops during the first few weeks
      of postnatal life which, e.g., is reflected in the temporal and regional
      regulation of the neuronal progenitor marker Ascl1. The most dorsomedial zone
      shows significantly fewer cells in S-phase in the adult but not in newborn mice
      by two different measures. Moreover, we show that there are regional differences
      in the relative differentiation, cell survival, and thickness of the olfactory
      epithelium. These findings are compatible with the view that zones are inherently
      distinct and that such differences contribute to generate regional differences in
      cellular homeostasis that in turn may modulate the capacity of a region to adjust
      to extrinsic influence.

PMID- 19177520
TI  - Parallel screening and optimization of protein constructs for structural studies.
AB  - A major challenge in structural biology remains the identification of protein
      constructs amenable to structural characterization. Here, we present a simple
      method for parallel expression, labeling, and purification of protein constructs
      (up to 80 kDa) combined with rapid evaluation by NMR spectroscopy. Our approach,
      which is equally applicable for manual or automated implementation, offers an
      efficient way to identify and optimize protein constructs for NMR or X-ray
      crystallographic investigations.

PMID- 19177522
TI  - Variation in age and physical status prior to total knee and hip replacement
      surgery: a comparison of centers in Australia and Europe.
AB  - OBJECTIVE: To investigate whether variation exists in the preoperative age, pain,
      stiffness, and physical function of people undergoing total knee replacement
      (TKR) and total hip replacement (THR) at several centers in Australia and Europe.
      METHODS: Individual Western Ontario and McMaster Universities Osteoarthritis
      Index data (range 0-100, where 0 = best and 100 = worst) collected within 6 weeks
      prior to primary TKR and THR were extracted from 16 centers (n = 2,835) according
      to specified eligibility criteria. Analysis of covariance was used to evaluate
      differences in pain, stiffness, and physical function between centers, with
      adjustment for age and sex. RESULTS: There was marked variation in the age of
      people undergoing surgery between the centers (TKR mean age 67-73 years;
      F[6,1004] = 4.21, P < 0.01, and THR mean age 63-72 years; F[14,1807] = 7.27, P <
      0.01). Large differences in preoperative status were observed between centers,
      most notably for pain (TKR adjusted mean pain 52.5-61.1; F[6,1002] = 4.26, P <
      0.01, and THR adjusted mean pain 49.2-65.7; F[14,1802] = 8.44, P < 0.01) and
      physical function (TKR adjusted mean function 52.7-61.4; F[6,1002] = 5.27, P <
      0.01, and THR adjusted mean function 53.3-71.0; F[14,1802] = 6.71, P < 0.01).
      Large effect sizes (up to 0.98) reflect the magnitude of variation between
      centers and highlight the clinical relevance of these findings. CONCLUSION: The
      large variations in age and preoperative status indicate substantial differences
      in the timing of joint replacement across the centers studied, with potential for
      compromised surgical outcomes due to premature or delayed surgery. Possible
      contributing factors include patient preferences, the absence of concrete
      indications for surgery, and the capacity of the health care systems.

PMID- 19177523
TI  - Physical activity and incident clinical knee osteoarthritis in older adults.
AB  - OBJECTIVE: To study the relationship between 4 components of physical activity
      and the 12-year incidence of clinical knee osteoarthritis (OA) among older
      adults. METHODS: Longitudinal data from 1,678 men and women, ages 55-85 years,
      were collected in the Longitudinal Aging Study Amsterdam. Incident clinical knee
      OA was defined by an algorithm using self-report and general practitioner data.
      Physical activity was assessed by a validated questionnaire from which 4 physical
      activity component scores were created: muscle strength, intensity, mechanical
      strain, and turning actions. Cox proportional hazards models were conducted to
      examine the relationship between these scores and incident knee OA and reported
      as hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: During
      12 years of followup, 463 respondents (28%) developed clinical knee OA. A high
      mechanical strain score (HR 1.43, 95% CI 1.15-1.77) and a low muscle strength
      score (HR 1.30, 95% CI 1.01-1.68) were associated with an increased risk of knee
      OA after adjustment for age, sex, region of living, education, lifetime physical
      work demands, lifetime general physical activity, body mass index, current total
      physical activity level, and depression. No association was observed in the
      intensity and turning actions components. The results were similar for men and
      women, and for obese and nonobese respondents. CONCLUSION: Older adults who
      perform low muscle strength activities or activities causing high mechanical
      strain had an increased risk of clinical knee OA. These results suggest that
      specific components of physical activity may influence the development of knee
      OA.

PMID- 19177521
TI  - Economic burden of knee and hip osteoarthritis in Spain.
AB  - OBJECTIVE: To estimate the direct and indirect osteoarthritis (OA)-attributable
      costs and predictors of costs of knee and hip OA in Spain. METHODS: This study
      included consecutive patients age > or = 50 years with symptomatic and radiologic
      knee and/or hip OA who were seen at primary care centers in all provinces of
      Spain. Information on demographics, health status (Short Form 12 Health Survey),
      comorbidities (Charlson Index), clinical (Western Ontario and McMaster
      Universities Osteoarthritis Index [WOMAC]) and radiologic OA severity
      (Kellgren/Lawrence [K/L] scale), data related to OA health resources utilization
      (medical and nonmedical), and subjects' and caregivers' expenses and time lost in
      the previous 6 months were collected in 2 separate, structured, and detailed
      interviews. Costs in euros were assigned using market prices and official sources
      if available, and were annualized (to 2007). The predictors of costs were
      assessed in multivariate regression models. Costs were log-transformed before
      being modeled. RESULTS: A total of 1,071 subjects were analyzed (74% women, mean
      +/- SD age 71 +/- 9 years). Average total annual costs were euro1,502 per
      patient. Direct costs accounted for 86% of the total cost. We estimated a
      national cost of euro4,738 million, representing 0.5% of the gross national
      product. Higher total costs were associated with comorbidity (Charlson Index odds
      ratio [OR] 1.27, 95% confidence interval [95% CI] 1.03-1.58), poorer health
      status (P < 0.050), worse WOMAC scores (OR 1.05, 95% CI 1.03-1.08), and grade 4
      K/L scores (OR 1.76, 95% CI 1.15-2.69). CONCLUSION: The economic burden of knee
      and hip OA is substantial. Costs increased with comorbidity, poorer health
      status, and clinical and radiologic OA severity.

PMID- 19177524
TI  - Exercise prescription for chronic back or neck pain: who prescribes it? who gets
      it? What is prescribed?
AB  - OBJECTIVE: To describe exercise prescription in routine clinical practice for
      individuals with chronic back or neck pain because, although current practice
      guidelines promote exercise for chronic back and neck pain, little is known about
      exercise prescription in routine care. METHODS: We conducted a computer-assisted
      telephone survey of a representative sample of individuals (n = 684) with chronic
      back or neck pain who saw a physician, chiropractor, and/or physical therapist
      (PT) in the past 12 months. Individuals were asked about whether they were
      prescribed exercise, the amount of supervision received, and the type, duration,
      and frequency of the prescribed exercise. Descriptive and multivariable
      regression analyses were conducted. RESULTS: Of the 684 subjects, 48% were
      prescribed exercise. Of those prescribed exercise, 46% received the prescription
      from a PT, 29% from a physician, 21% from a chiropractor, and 4% from other. In
      multivariable analyses, seeing a PT or a chiropractor were the strongest
      predictors of exercise prescription. The likelihood of exercise prescription was
      increased in women, those with higher education, and those receiving worker's
      compensation. PTs were more likely to provide supervision and prescribe
      strengthening exercises compared with physicians and chiropractors, and were more
      likely to prescribe stretching exercises compared with physicians. CONCLUSION:
      Our findings suggest that exercise is being underutilized as a treatment for
      chronic back and neck pain and, to some extent, that the amount of supervision
      and types of exercises prescribed do not follow current practice guidelines.
      Exercise prescription provided by PTs appears to be most in line with current
      guidelines.

PMID- 19177525
TI  - Health-related quality of life for patients with vasculitis and their spouses.
AB  - OBJECTIVE: Chronic disease affects both patients and spouses, yet the effect of
      vasculitis on the spouses of patients has not been systematically examined. We
      addressed this research gap by describing 8 dimensions of health-related quality
      of life (HRQOL) for antineutrophil cytoplasmic antibody-associated vasculitis
      (AAV) patients and their spouses and compared patients and spouses with norms for
      the general US population. We also determined whether the impact of AAV on HRQOL
      differs by sex for patients or their spouses. METHODS: Ninety-seven patients with
      AAV and their spouses completed a mailed questionnaire that included demographic
      information and a measure of HRQOL (Medical Outcomes Study Short Form 36.) Using
      the RAND method, we calculated 8 HRQOL dimensions: general health, physical
      functioning, emotional role limitations, physical role limitations, social
      functioning, mental health, bodily pain, and energy/vitality. Using norm-based
      scores, we compared the HRQOL of patients and spouses with the general US
      population. We then used multivariate analysis of covariance (MANCOVA) test for
      sex differences in HRQOL for patients and spouses. RESULTS: Patients with AAV
      scored lower than the US norm on all HRQOL subscales with the exception of bodily
      pain. In contrast, spouses scored similarly to national norms. When age,
      education, race, illness duration, and disease severity were controlled, there
      were no significant sex differences in HRQOL for patients or spouses. CONCLUSION:
      AAV negatively impacts HRQOL for patients; whereas, spouses do not appear to be
      as negatively impacted. Long-term marriages may attenuate the effect of sex on
      HRQOL. Quality of life should be assessed throughout the disease course for both
      patients and spouses.

PMID- 19177526
TI  - Depression, medication adherence, and service utilization in systemic lupus
      erythematosus.
AB  - OBJECTIVE: Forgetting to take medications is an important cause of nonadherence.
      This study evaluated factors associated with forgetting to take medications in a
      large cohort of persons with systemic lupus erythematosus (SLE) participating in
      the University of California, San Francisco Lupus Outcomes Study (LOS).
      Relationships among adherence problems and service utilization (outpatient
      visits, emergency department visits, and hospitalizations) were also evaluated.
      METHODS: The cohort consisted of 834 LOS participants who provided self-reported
      frequency of forgetting to take medications as directed. Predictors of adherence
      and service utilization patterns included self-reported sociodemographics,
      disease-related characteristics (e.g., disease activity, recent SLE flare), and
      mental health characteristics (Center for Epidemiologic Studies Depression Scale
      and cognitive function screen). Health care utilization patterns included the
      presence and quantity of visits to rheumatologists, primary care physicians,
      other care providers, emergency departments, and hospitalizations. RESULTS: Forty
      six percent of the LOS cohort reported forgetting to take medications at least
      some of the time. Depressive symptom severity was a strong predictor of adherence
      difficulties (odds ratio [OR] 1.04, 95% confidence interval [95% CI] 1.02-1.05; P
      < 0.0001) after accounting for all other predictors. Persons reporting adherence
      difficulties had significantly greater numbers of outpatient rheumatology and
      primary care visits, and were more likely to visit the emergency department (OR
      1.45, 95% CI 1.04-2.04; P = 0.03). CONCLUSION: Depression may be an important
      cause of medication adherence problems, and difficulties with adherence are
      significantly associated with high-cost service utilization, specifically
      emergency department visits. In an era of rapidly evolving treatments for lupus,
      identifying patients at risk for adherence problems may decrease medical
      expenditures and improve patient outcomes in SLE.

PMID- 19177529
TI  - Tendinopathy and statin use: the role of matrix metalloproteinases or
      eicosanoids? Comment on the letter by Beri and Khattri and the article by Marie
      et al.

PMID- 19177530
TI  - Efficacy of multicomponent treatment in fibromyalgia syndrome: a meta-analysis of
      randomized controlled clinical trials.
AB  - OBJECTIVE: To systematically review the efficacy of multicomponent treatment of
      fibromyalgia syndrome (FMS). METHODS: We screened Medline, PsychINFO, Scopus, and
      the Cochrane Library (through December 2007), as well as reference sections of
      original studies, reviews, and evidence-based guidelines. Randomized controlled
      trials (RCTs) on the multicomponent treatment (at least 1 educational or other
      psychological therapy with at least 1 exercise therapy) of FMS were analyzed.
      RESULTS: We included 9 (of 14) RCTs with 1,119 subjects (median treatment time 24
      hours) in the meta-analysis. Effects were summarized using standardized mean
      differences (SMDs) or weighted mean differences (WMDs). There was strong evidence
      that multicomponent treatment reduces pain (SMD -0.37; 95% confidence interval
      [95% CI] -0.62, -0.13), fatigue (WMD -0.85; 95% CI -1.50, -0.20), depressive
      symptoms (SMD -0.67; 95% CI -1.08, -0.26), and limitations to health-related
      quality of life (HRQOL) (SMD -0.59; 95% CI -0.90, -0.27) and improves self
      efficacy pain (SMD 0.54; 95% CI 0.26, 0.82) and physical fitness (SMD 0.30; 95%
      CI 0.02, 0.57) at posttreatment. There was no evidence of its efficacy on pain,
      fatigue, sleep disturbances, depressive symptoms, HRQOL, or self-efficacy pain in
      the long term. There was strong evidence that positive effects on physical
      fitness (SMD 0.30; 95% CI 0.09, 0.51) can be maintained in the long term (median
      followup 7 months). CONCLUSIONS: There is strong evidence that multicomponent
      treatment has beneficial short-term effects on the key symptoms of FMS.
      Strategies to maintain the benefits of multicomponent treatment in the long term
      need to be developed.

PMID- 19177531
TI  - Ten novel HMGCL mutations in 24 patients of different origin with 3-hydroxy-3
      methyl-glutaric aciduria.
AB  - 3-Hydroxy-3-methylglutaric aciduria is a rare autosomal recessive genetic
      disorder that affects ketogenesis and L-leucine catabolism. The clinical acute
      symptoms include vomiting, convulsions, metabolic acidosis, hypoketotic
      hypoglycaemia and lethargy. To date, 33 mutations in 100 patients have been
      reported in the HMGCL gene. In this study 10 new mutations in 24 patients are
      described. They include: 5 missense mutations: c.109G>A, c.425C>T, c.521G>A,
      c.575T>C and c.598A>T, 2 nonsense mutations: c.242G>A and c.559G>T, one small
      deletion: c.853delC, and 2 mutations in intron regions: c.497+4A>G and
      c.750+1G>A. Two prevalent mutations were detected, 109G>T (E37X) in 38% of
      disease alleles analyzed and c.504_505delCT in 10% of them. Although patients are
      mainly of European origin (71%) and mostly Spanish (54%), the group is ethnically
      diverse and includes, for the first time, patients from Pakistan, Palestine and
      Ecuador. We also present a simple, efficient method to express the enzyme and we
      analyze the possible functional effects of missense mutations. The finding that
      all identified missense mutations cause a >95% decrease in the enzyme activity,
      indicates that the disease appears only in very severe genotypes."

PMID- 19177532
TI  - Mutations in MFSD8/CLN7 are a frequent cause of variant-late infantile neuronal
      ceroid lipofuscinosis.
AB  - The neuronal ceroid lipofuscinoses (NCL) are a group of genetically heterogeneous
      neurodegenerative disorders. The recent identification of the MFSD8/CLN7 gene in
      a variant-late infantile form of NCL (v-LINCL) in affected children from Turkey
      prompted us to examine the relative frequency of variants in this gene in Italian
      patients with v-LINCL. We identified nine children harboring 11 different
      mutations in MFSD8/CLN7. Ten mutations were novel and included three nonsense
      (p.Arg35Stop, p.Glu381Stop, p.Arg482Stop), four missense (p.Met1Thr, p.Gly52Arg,
      p.Thr294Lys, p.Pro447Leu), two splice site mutations (c.863+3_4insT, c.863+1G>C),
      and a 17-bp deletion predicting a frameshift and premature protein truncation
      (c.627_643del17/p.Met209IlefsX3). The clinical phenotype, which was similar to
      that of the Turkish v-LINCL cases, was not influenced by type and location of the
      mutation nor the length of the predicted residual gene product. As well as
      identifying novel variants in MFSD8/CLN7, this study contributes to a better
      molecular characterization of Italian NCL cases, and will facilitate medical
      genetic counseling in such families. The existence of a subset of v-LINCL cases
      without mutations in any of the known NCL genes suggests further genetic
      heterogeneity.

PMID- 19177533
TI  - Self-report and physical performance measures of physical function in hip
      osteoarthritis: relationship to isometric quadriceps torque development.
AB  - OBJECTIVE: Quadriceps strength (knee extensor torque) is an important correlate
      of physical function in individuals with hip osteoarthritis (OA). However, it
      remains unclear whether the ability to rapidly generate quadriceps torque in the
      early phase of muscle contraction (maximal rate of torque development [MRTD]) is
      also associated with physical function. The purpose of this study was to quantify
      the independent impact of quadriceps strength and quadriceps MRTD on self-report
      and physical performance measures of physical function in community-dwelling
      adults with hip OA. METHODS: Ninety-two adults with radiographically confirmed
      symptomatic hip OA (mean age 62 years) participated. Unilateral isometric
      quadriceps strength and MRTD were measured using a dynamometer. Self-report
      measure of physical function was assessed by the Short Form 36 (SF-36)
      questionnaire, and physical performance was assessed by the timed stair and step
      tests. RESULTS: In the hierarchical regression models, high maximal quadriceps
      strength and high quadriceps MRTD uniquely covaried with high SF-36 physical
      function scores after accounting for demographic, anthropometric, and pain
      measures. For the timed stair test, all else being equal, in 2 participants with
      low but identical levels of quadriceps strength, the one with a higher MRTD had
      better stair-climbing function. For the step test, quadriceps MRTD was not
      associated with step test performance over and above that of quadriceps strength.
      CONCLUSION: In individuals with hip OA, maximal quadriceps strength and
      quadriceps MRTD positively impact self-report and physical performance measures
      of physical function. These findings are of importance in developing intervention
      strategies, but they call for further study.

PMID- 19177534
TI  - Time to diagnosis in systemic sclerosis: is sex a factor?
AB  - OBJECTIVE: To determine whether sex plays a role in the time to diagnosis of
      systemic sclerosis (SSc). METHODS: In the Canadian Scleroderma Research Group
      registry, dates of onset of Raynaud's phenomenon, the first non-Raynaud's disease
      symptom, and diagnosis were recorded based on patient reports. Association
      between sex and time to diagnosis was assessed for the group as a whole and
      stratified based on extent of skin involvement, either limited or diffuse.
      RESULTS: Of the 408 patients studied (347 women, 61 men, 44% with diffuse
      cutaneous SSc), the time to diagnosis after the onset of Raynaud's phenomenon was
      significantly longer for women than men (log rank P = 0.001), but not
      significantly different after the onset of the first non-Raynaud's disease
      manifestation. In an analysis stratified by limited or diffuse status, the time
      to diagnosis from onset of Raynaud's phenomenon was also significantly longer for
      women than men with diffuse cutaneous SSc (log rank P = 0.008). A trend toward a
      longer period between onset of Raynaud's phenomenon and SSc diagnosis was
      observed in women compared with men with limited cutaneous SSc (median 4.6 years
      in women versus 2.1 years in men; P = 0.085), and there was no sex difference in
      time to diagnosis after the onset of the first non-Raynaud's disease
      manifestation. CONCLUSION: In SSc, the time to diagnosis is longer for women than
      men after the onset of Raynaud's phenomenon, suggesting that there may be
      possible biologic differences in the progression of disease or in the health care
      trajectories of men and women with early SSc.

PMID- 19177535
TI  - Prognostic factors in adults with knee pain in general practice.
AB  - OBJECTIVE: To predict the 1-year outcome of incident nontraumatic knee symptoms
      in adults presenting in general practice. METHODS: Adults age >35 years with
      nontraumatic knee symptoms (n = 480) were followed for 1 year. At baseline, data
      on knee symptoms and demographics were collected and a physical examination
      performed. Knee symptoms were assessed by self-report questionnaires at 3-month
      intervals. After 1 year the physical examination was repeated. Multivariate
      prognostic regression models of patient characteristics, symptom characteristics,
      and physical examination were used to predict persisting knee symptoms after 1
      year. Areas under receiving operating characteristic curves (AUCs) were used to
      determine the predictive value of the model. To assess the added predictive value
      of symptom characteristics and physical examination, these models were added to
      the model of patient characteristics. The improvement was expressed as the
      difference between the 2 AUCs. RESULTS: In the multivariate prognostic model of
      patient characteristics, age >60 years, educational level, kinesophobia, and
      comorbidity of the skeletal system were associated with persistent knee symptoms
      after 1 year (AUC 0.67). Of the symptom characteristics, history of nontraumatic
      knee symptoms, bilateral symptoms, and duration of symptoms >3 months were
      associated (AUC 0.73). For determinants of physical examination, crepitus of
      passive extension was associated (AUC 0.55). The added value of the symptom
      characteristics model to the patient characteristics model was 0.09 (AUC 0.76).
      Physical examination added no further value. CONCLUSION: Symptom characteristics
      are the strongest predictors of persisting knee symptoms at 1-year followup.
      Physical examination has no added value in predicting persistent knee symptoms in
      general practice.

PMID- 19177536
TI  - Land-based versus water-based rehabilitation following total knee replacement: a
      randomized, single-blind trial.
AB  - OBJECTIVE: To compare outcomes between land-based and water-based exercise
      programs delivered in the early subacute phase up to 6 months after total knee
      replacement (TKR). METHODS: Two weeks after surgery (baseline), 102 patients were
      randomized to participate in either land-based (n = 49) or water-based (n = 53)
      exercise classes. Treatment parameters were guided by current clinical practice
      protocols. Therefore, each study arm involved 1-hour sessions twice a week for 6
      weeks, with patient-determined exercise intensity. Session attendance was
      recorded. Outcomes were measured at baseline and at 8 and 26 weeks postsurgery.
      Outcomes included distance on the 6-Minute Walk test, stair climbing power (SCP),
      the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index (n =
      85 English-proficient patients), visual analog scale for joint pain, passive knee
      range of motion, and knee edema (circumference). Planned orthogonal contrasts,
      with an intent-to-treat approach, were used to analyze the effects of time and
      time-group interactions. RESULTS: Compliance in both groups was excellent with
      81% attending 8 or more sessions. Loss to followup was 5%. Significant
      improvements were observed across time in all outcomes at 8 weeks, with further
      improvements evident in all variables (except WOMAC pain) at 26 weeks. Minor
      between-group differences were evident for 4 outcomes (SCP, WOMAC stiffness,
      WOMAC function, and edema) but these appear clinically insignificant. CONCLUSION:
      A short-term, clinically pragmatic program of either land-based or water-based
      rehabilitation delivered in the early phase after TKR was associated with
      comparable outcomes at the end of the program and up to 26 weeks postsurgery.

PMID- 19177538
TI  - Facilitated bone mineral density testing versus hospital-based case management to
      improve osteoporosis treatment for hip fracture patients: additional results from
      a randomized trial.
AB  - OBJECTIVE: We previously demonstrated that a case manager intervention improved
      osteoporosis (OP) treatment within 6 months of hip fracture compared with usual
      care. The second phase of the randomized trial compared a less intensive
      intervention, facilitated bone mineral density (BMD) testing, with usual care and
      the case manager intervention. METHODS: We initially randomized 220 hip fracture
      patients to either an OP case manager intervention or usual care. After
      completing the original trial at 6 months postfracture, usual care patients were
      reallocated to facilitated BMD testing; BMD tests were arranged and results sent
      to primary care physicians. Main outcomes (bisphosphonate treatment, BMD tests,
      receipt of appropriate care) were reascertained 1 year following hip fracture and
      compared with outcomes achieved by the OP case manager intervention and usual
      care. RESULTS: Compared with usual care, facilitated BMD testing increased
      testing from 29% to 68% (P < 0.001), bisphosphonate use from 22% to 38% (P <
      0.001), and receipt of appropriate care from 26% to 45% (P < 0.001). The more
      intensive (70 versus 30 minutes) and expensive ($56 versus $24 Canadian per
      patient) OP case manager intervention led to significantly higher bisphosphonate
      use (54% versus 38%; P = 0.03), receipt of appropriate care (71% versus 45%; P <
      0.001), and more BMD testing (80% versus 68%; P = 0.06) than usual care followed
      by facilitated BMD testing. CONCLUSION: Compared with usual care, 2 different
      inexpensive interventions resulted in significant increases in appropriate
      management of OP after hip fracture. The magnitude of improvements achieved was
      directly related to the intensity of the interventions.

PMID- 19177539
TI  - Cardiovascular and gastrointestinal risks of nonsteroidal antiinflammatory drugs
      revisited: comment on the article by the American College of rheumatology Ad Hoc
      group on use of selective and nonselective nonsteroidal antiinflammatory drugs.

PMID- 19177540
TI  - Pregnancy in patients with ankylosing spondylitis: do regulatory T cells play a
      role?
AB  - OBJECTIVE: To investigate the numerical and functional changes of CD4+CD25(high)
      regulatory T (Treg) cells during pregnancy and postpartum in patients with
      ankylosing spondylitis (AS). METHODS: The frequency of CD4+CD25(high) T cells was
      determined by flow cytometry in 10 pregnant and 5 nonpregnant patients with AS as
      well as in 14 pregnant and 4 nonpregnant healthy controls. Pregnant individuals
      were investigated at the third trimester and 8 weeks postpartum. Treg cells and
      CD4+CD25- effector T (Teff) cells separated by fluorescence-activated cell
      sorting were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies, alone
      or in coculture, to investigate proliferation and cytokine secretion. RESULTS:
      The frequency of CD4+CD25(high) Treg cells was significantly higher during
      pregnancy than postpartum in both healthy control subjects and patients with AS.
      In contrast to Treg cells in healthy pregnant women, Treg cells in pregnant women
      with AS secreted only small amounts of interleukin-10 and showed lower
      suppression of tumor necrosis factor alpha and interferon-gamma secretion by
      CD4+CD25- Teff cells. At the postpartum time point, proinflammatory cytokine
      levels in the Treg/Teff cell cocultures and Teff cell monocultures were
      significantly higher in patients with AS than in healthy controls. CONCLUSION:
      Pregnancy influenced the expansion and cytokine secretion of Treg cells in both
      patients with AS and control subjects. However, the Treg cells of pregnant
      patients with AS failed to support an antiinflammatory cytokine milieu, thereby
      possibly contributing to the persistent disease activity of AS during pregnancy.

PMID- 19177541
TI  - Serum uric acid level as an independent risk factor for all-cause,
      cardiovascular, and ischemic stroke mortality: a Chinese cohort study.
AB  - OBJECTIVE: The association between hyperuricemia and cardiovascular events has
      been documented in high-risk groups, but is still undetermined in general
      populations, especially Chinese. This study assessed the temporal association
      between serum uric acid level, hyperuricemia, and cardiovascular mortality.
      METHODS: A prospective cohort study of 41,879 men and 48,514 women ages > or = 35
      years was conducted using data from the MJ Health Screening Centers in Taiwan.
      Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke,
      congestive heart failure, hypertensive disease, and coronary heart disease were
      compared according to increasing serum uric acid levels. RESULTS: A total of
      1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup
      8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7
      mg/dl) were estimated with Cox regression model after adjusting for age, sex,
      body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy
      cigarette smoking, and frequent alcohol consumption. In all patients, HRs were
      1.16 (P < 0.001) for all-cause mortality, 1.39 (P < 0.001) for total CVD, and
      1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for
      cardiovascular risk remained significant in patients with hypertension (1.44, P <
      0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low
      metabolic risk subgroup, the HRs for all-cause mortality and total cardiovascular
      morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively. CONCLUSION:
      Hyperuricemia was an independent risk factor of mortality from all causes, total
      CVD, and ischemic stroke in the Taiwanese general population, in high-risk
      groups, and potentially in low-risk groups.

PMID- 19177542
TI  - Improved function from progressive strengthening interventions after total knee
      arthroplasty: a randomized clinical trial with an imbedded prospective cohort.
AB  - OBJECTIVE: To determine the effectiveness of progressive quadriceps strengthening
      with or without neuromuscular electrical stimulation (NMES) on quadriceps
      strength, activation, and functional recovery after total knee arthroplasty
      (TKA), and to compare progressive strengthening with conventional rehabilitation.
      METHODS: A randomized controlled trial was conducted between July 2000 and
      November 2005 in an academic outpatient physical therapy clinic. Two hundred
      patients who had undergone primary, unilateral TKA for knee osteoarthritis were
      randomized to 1 of 2 interventions 4 weeks after surgery, and 41 patients
      eligible for enrollment who did not participate in the intervention were tested
      12 months after surgery (standard of care group). All randomized patients
      received 6 weeks of outpatient physical therapy 2 or 3 times per week through 1
      of 2 intervention protocols: an exercise group (volitional strength training) or
      an exercise-NMES group (volitional strength training and NMES). Treatment effects
      were evaluated by a burst superimposition test to assess quadriceps strength and
      volitional activation 3 and 12 months postoperatively. The Medical Outcomes Study
      Short Form 36 and Knee Outcome Survey were completed. Knee range of motion, Timed
      Up and Go, Stair-Climbing Test, and 6-Minute Walk were also measured. RESULTS:
      Strength, activation, and function were similar between the exercise and exercise
      NMES groups at 3 and 12 months. The standard of care group was weaker and
      exhibited worse function at 12 months compared with both treatment groups.
      CONCLUSION: Progressive quadriceps strengthening with or without NMES enhances
      clinical improvement after TKA, achieving similar short- and long-term functional
      recovery and approaching the functional level of healthy older adults.
      Conventional rehabilitation does not yield similar outcomes.

PMID- 19177544
TI  - Incidence and clinical predictors of psoriatic arthritis in patients with
      psoriasis: a population-based study.
AB  - OBJECTIVE: To determine the incidence and disease-specific predictors of
      clinically recognized psoriatic arthritis (PsA) in patients with psoriasis.
      METHODS: We identified an incidence cohort of psoriasis subjects age >/=18 years
      diagnosed between January 1, 1970 and December 31, 1999 in a population-based
      setting. Psoriasis diagnoses were validated by confirmatory diagnosis in the
      medical record. Incident and clinically recognized PsA subjects were classified
      according to the Classification of Psoriatic Arthritis (CASPAR) criteria. Cox
      proportional hazards models were used to identify predictors of PsA within the
      psoriasis cohort. RESULTS: The psoriasis incidence cohort comprised 1,633
      subjects. Of these, 40 were diagnosed with PsA concurrently with psoriasis and
      were excluded from analysis. The remaining 1,593 psoriasis subjects had a mean
      age of 43 years and 50% were men. Over 20,936 person-years of followup, 57
      subjects were clinically recognized with new-onset PsA, with a cumulative
      incidence of 1.7% (95% confidence interval [95% CI] 1.0-2.3%), 3.1% (95% CI 2.2
      4.1%), and 5.1% (95% CI 3.7-6.6%) at 5, 10, and 20 years following psoriasis
      incidence, respectively. Psoriasis features associated with higher risk of PsA
      were scalp lesions (hazard ratio [HR] 3.89, 95% CI 2.18-6.94), nail dystrophy (HR
      2.93, 95% CI 1.68-5.12), and intergluteal/perianal lesions (HR 2.35, 95% CI 1.32
      4.19). Calendar year was not associated with risk of PsA (P = 0.15), indicating
      that the likelihood of PsA in psoriasis subjects did not change over time.
      CONCLUSION: In this population-based study, <10% of patients with psoriasis
      developed clinically recognized PsA during a 30-year period. Psoriasis features
      associated with a higher likelihood of PsA were nail dystrophy, scalp lesions,
      and intergluteal/perianal psoriasis.

PMID- 19177545
TI  - Rheumatology fellows' perception on training and careers in academia: the
      American College of Rheumatology Fellow Research and Academic Training Survey.
AB  - OBJECTIVE: To examine the perceptions of rheumatology fellows regarding their
      research training, mentoring, and interest in a career in academia. METHODS: We
      solicited by e-mail 386 fellows in the American College of Rheumatology 2005-2006
      fellow database to take an anonymous Internet-based survey addressing the topics
      of research training, mentoring, and interest in an academic career. RESULTS: We
      received 176 responses (50% response rate after excluding invalid contacts) to
      the survey. During their training, 58% of fellows reported an interest in
      academia and 21% in research. There was great satisfaction with mentoring.
      However, there were concerns about academic salaries, with 50% of respondents
      stating a preference for a higher paying community position. Furthermore, there
      were substantial concerns about the difficulty of generating funds to cover
      salaries. In addition, several respondents viewed an academic career as
      incompatible with starting a family. Compared with male fellows, female fellows
      were more likely to want a career in academics, were less concerned about
      academic salaries, and were more concerned about funding and family life.
      CONCLUSION: Despite an interest in academia and satisfaction with current
      mentoring, several barriers to academia were identified among rheumatology
      fellows. The concern that academia and family life are incompatible needs further
      attention. University deans should consider reevaluating promotion programs to
      make allowances for family and parenting demands. Rheumatology division chairs
      should better promote the nonfinancial rewards of a career in academia. Programs
      such as the National Institutes of Health Loan Repayment Program should be
      strongly advertised to interested applicants with financial concerns.

PMID- 19177548
TI  - In flux on infliximab: conflicting studies on surgical outcomes.

PMID- 19177546
TI  - Work loss and work entry among persons with systemic lupus erythematosus:
      comparisons with a national matched sample.
AB  - OBJECTIVE: To prospectively track work loss among those employed and work entry
      among those not employed in a cohort of persons with systemic lupus erythematosus
      (SLE), assess risk factors for these outcomes, and compare rates of the outcomes
      with a matched national sample. METHODS: The present study analyzed 4 years of
      data from the Lupus Outcomes Study (LOS), augmented by information on the local
      labor market from the Census Bureau and the Bureau of Labor Statistics. We used
      the Kaplan-Meier method to assess time from study initiation until work loss or
      work entry, and Cox proportional hazards regression to estimate factors affecting
      these outcomes. Finally, we compared rates of work loss and work entry in the LOS
      with rates in the Survey of Income and Program Participation (SIPP). RESULTS: At
      study initiation, 394 LOS participants (51%) were employed, of whom 92 (23.4%)
      experienced work loss. In multivariate analysis, older age, lower cognitive and
      physical functioning, and higher reports of depressive symptoms predicted work
      loss. In comparison with the SIPP sample, rates of work loss did not differ. Of
      the 376 LOS participants not employed, 76 (20.2%) experienced work entry. In
      multivariate analysis, less disease activity, fewer lung manifestations, better
      physical functioning, and shorter time since last employment predicted work
      entry. In comparison with the SIPP, rates of work entry were only lower between
      ages 35 and 55 years. CONCLUSION: Until age 55 years, low rates of employment
      among persons with SLE may be due to lower rates of work entry rather than higher
      rates of work loss. Beyond age 55 years, both high rates of work loss and low
      rates of work entry contribute to low rates of employment.

PMID- 19177549
TI  - A mutation in the signal sequence of LRP5 in a family with an osteoporosis
      pseudoglioma syndrome (OPPG)-like phenotype indicates a novel disease mechanism
      for trinucleotide repeats.
AB  - We extend the spectrum of phenotypes caused by mutations in the Wnt/Norrin
      coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) by
      identifying two novel types of mutation in related individuals whose presenting
      features were profound muscle hypotonia, mild mental retardation, blindness, and
      growth retardation. One mutation removes 6 out of 9 consecutive leucine residues
      in the LRP5 signal peptide (c.43_60del or p.Leu15_Leu20del), which impairs
      polypeptide entry into the endoplasmic reticulum (ER), trafficking to the cell
      membrane, and signal transduction. The second mutation resulted from
      nonhomologous recombination between Alu repeat sequences, which deleted exons 14
      16 and would produce a nonfunctional, truncated, and frameshifted polypeptide, if
      expressed [chr11:g.(13871447_1387511)_(13879636_13879700)del (NW_925106.1) or
      p.Pro1010GlnfsX38]. We confirmed that the length of the LRP5 signal peptide poly
      leucine repeat is polymorphic in the general population, and, importantly, we
      were able to demonstrate in independent in vitro assays that different allele
      sizes affect receptor processing and signal transduction. Consequently, this
      polymorphism may have physiologic effects in vivo. This latter finding is
      relevant since through a genomewide search we identified nearly 400 human
      proteins that contain poly-leucine repeats within their signal peptide. We chose
      18 of these proteins and genotyped the underlying trinucleotide repeat in healthy
      Caucasian individuals. More than one length allele was observed in one-half of
      the proteins. We therefore propose that natural variation in poly-leucine
      stretches within signal peptides constitutes a currently unrecognized source of
      variability in protein translation and expression.

PMID- 19177550
TI  - Deletions removing the last exon of TACSTD1 constitute a distinct class of
      mutations predisposing to Lynch syndrome.
AB  - Several different genetic alterations in the etiology of Lynch syndrome
      (hereditary nonpolyposis colorectal cancer [HNPCC]) are known, mostly point
      mutations and genomic rearrangements in 1 of at least 3 mismatch-repair (MMR)
      genes. However, no susceptibility factor has yet been identified in a significant
      part (30-50%) of clinicopathologically well-defined HNPCC families, suggesting
      the presence of other predisposing mechanisms. In a set of probands from 27 Lynch
      syndrome families who lacked evidence of a germline mutation in either the MSH2
      or MLH1 gene, we performed genomic deletion screening with the use of multiplex
      ligation-dependent probe amplification (MLPA) and sequencing. We used
      immunohistochemistry (IHC) and microsatellite instability (MSI) analyses on
      samples of the probands of all families. Comparative analysis of mRNA transcripts
      was performed on blood leukocyte-derived samples from mutation carriers and
      noncarrier controls. We report that large germline deletions encompassing the
      last exons of the TACSTD1 gene, upstream of MSH2, cosegregate with the HNPCC
      phenotype in 19% (5/27) of families tested. The tumors of the carriers show high
      level MSI and MSH2 protein loss. We show that these deletions, by removing the
      transcriptional termination sequences of the upstream gene, give rise to multiple
      TACSTD1/MSH2 fusion transcripts. Our results provide evidence that deletions
      removing the last exon of TACSTD1 constitute a distinct class of mutations
      predisposing to Lynch syndrome. Thus, analysis of the 3' region of the TACSTD1
      gene should be included in the routine mutation screening protocols for HNPCC.

PMID- 19177554
TI  - Predictors and outcomes of persistent or age-limited registered criminal
      behavior: a 30-year longitudinal study of a Swedish urban population.
AB  - This study uses data from the longitudinal research program Individual
      Development and Adaptation, where an entire school-grade cohort of children in a
      middle-size Swedish city (n approximately 1.300) has been followed from ages 10
      to 43 and 48 for women and men, respectively. Our findings indicate that the
      patterns of offending across the life-course differ between genders, where males
      seem to initiate their offending earlier than females. Further, there are very
      few women on a persistent offending-trajectory. Focusing on precursors to as well
      as consequences of offending as indexed in official registers, our results
      indicate that individuals in the persistent offender group have the most
      pronounced adjustment problems in school- as well as in middle age. Individual
      characteristics and behaviors (e.g., aggression, hyperactivity, antisocial
      behavior) vary systematically between individuals with different developmental
      offending patterns. The combination of an unstable upbringing and own antisocial
      behavior seems to be especially predictive for criminality. For persistent
      offenders, the prevalence of alcohol and psychiatric problems at adult age is
      high for males and extremely high for females (nine out of ten and six out of ten
      for each of the two problem types for females). Further, the importance for
      adjustment of the two-dimensional variation in the number of crimes committed
      during adolescence and adult age seems to have been surprisingly well captured by
      the "crude" division into the four offender groups that were used.

PMID- 19177555
TI  - Living on the edge: life-history of olive baboons at Gashaka-Gumti National Park,
      Nigeria.
AB  - Baboons are the most successful and ubiquitous African primates, renowned for
      their behavioral and reproductive flexibility, which enable them to inhabit a
      wide variety of habitat types. Owing to a number of long-term field studies,
      comparative behavioral, developmental, demographic, and life-history data are
      available from several populations, but study sites show a heavy bias toward
      South and East African savannahs, with little research in West or Central Africa.
      Life-history data from such areas are important if we are fully to understand the
      nature of the environmental factors that limit baboon distribution. Here, we
      present demographic data for olive baboons at Gashaka-Gumti National Park (GGNP),
      Nigeria, collected from December 2000-February 2006, and use these data to test
      comparative models of baboon life-history. The GGNP habitat, which includes large
      areas of rainforest, is an environment in which baboons are little studied, and
      rainfall is much higher than at previous study sites. GGNP troop size data are
      presented from censuses, as well as life-history data for two troops, one of
      which is within the park and wild-feeding (Kwano troop), whereas the other dwells
      at the park edge, and supplements its diet by crop-raiding (Gamgam troop). Troop
      sizes at GGNP are small compared with other field sites, but fit within
      previously suggested ranges for baboons under these climatic conditions. Inter
      birth intervals in Kwano troop were long compared with most studied populations,
      and values were not as predicted by comparative models. Consistent with known
      effects of food enhancement, Gamgam troop experienced shorter inter-birth
      intervals and lower infant mortality than Kwano troop. We indicate some possible
      factors that exclude baboons from true rainforest, and suggest that the clearing
      of forests in Central and West Africa for agricultural land may allow baboons to
      extend their range into regions from which they are currently excluded.

PMID- 19177556
TI  - Reduction of type IIb myosin and IIB fibers in tibialis anterior muscle of mini
      muscle mice from high-activity lines.
AB  - Selective breeding of laboratory house mice (Mus domesticus) for high voluntary
      wheel running has generated four replicate lines that show an almost threefold
      increase in daily wheel-running distances as compared with four nonselected
      control lines. An unusual hindlimb "mini-muscle" phenotype (small muscles,
      increased mitochondrial enzyme levels, disorganized fiber distribution) has
      increased in frequency in two of the four replicate selected lines. The gene of
      major effect that accounts for this phenotype is an autosomal recessive that has
      been mapped to a 2.6335 Mb interval on MMU11, but not yet identified. This study
      examined the tibialis anterior muscle to determine whether changes in muscle
      fiber types could explain such modifications in muscle size and properties.
      Although selected and control lines did not exhibit systematic differences in the
      fiber types present in the tibialis anterior muscle, as assessed by
      electrophoresis of myosin heavy chains (MHC) and by histochemistry, mini-muscle
      mice lacked type IIB fibers and the corresponding MHCs. Mini-muscle tibialis show
      increased activities of hexokinase and citrate synthase compared with the
      normally sized muscles, likely the result of the modified fiber types in the
      muscle. The mini-muscle phenotype is the major means through which selective
      breeding for high wheel running has modified the functional capacities of the
      hindlimb muscles, as normally sized tibialis anterior muscles from control and
      selected lines did not show general differences in their enzymatic capacities,
      MHC profiles or fiber type composition, with the exception of an elevated
      hexokinase activity and a reduced GPa activity in the selected lines.

PMID- 19177557
TI  - Connexin57 is expressed in dendro-dendritic and axo-axonal gap junctions of mouse
      horizontal cells and its distribution is modulated by light.
AB  - Mouse horizontal cells are coupled by gap junctions composed of connexin57. These
      gap junctions are regulated by ambient light via multiple neuromodulators
      including dopamine. In order to analyze the distribution and structure of
      horizontal cell gap junctions in the mouse retina, and examine the effects of
      light adaptation on gap junction density, we developed antibodies that detect
      mouse retinal connexin57. Using immunohistochemistry in retinal slices, flat
      mounted retinas, and dissociated retinal cells, we showed that connexin57 is
      expressed in the dendrites and axon terminal processes of mouse horizontal cells.
      No staining was found in retinas of connexin57-deficient mice. Significantly more
      connexin57-positive puncta were found in the distal than in the proximal outer
      plexiform layer, indicating a higher level of expression in axon terminal
      processes than in the dendrites. We also examined the gap junctions using
      immunoelectron microscopy and showed that connexin57 does not form hemichannels
      in the horizontal cell dendritic tips. Light adaptation resulted in a significant
      increase in the number of connexin57-immunoreactive plaques in the outer
      plexiform layer, consistent with previously reported effects of light adaptation
      on connexin57 expression in the mouse retina. This study shows for the first time
      the detailed location of connexin57 expression within mouse horizontal cells, and
      provides the first ultrastructural data on mouse horizontal cell gap junctions.

PMID- 19177559
TI  - Engineering antibody fragments to fold in the absence of disulfide bonds.
AB  - Disulfide bonds play a critical role in the stabilization of the immunoglobulin
      beta-sandwich sandwich. Under reducing conditions, such as those that prevail in
      the cytoplasm, disulfide bonds do not normally form and as a result most
      antibodies expressed in that compartment (intrabodies) accumulate in a misfolded
      and inactive state. We have developed a simple method for the quantitative
      isolation of antibody fragments that retain full activity under reducing
      conditions from large mutant libraries. In E. coli, inactivation of the cysteine
      oxidoreductase DsbA abolishes protein oxidation in the periplasm, which leads to
      the accumulation of scFvs and other disulfide-containing proteins in a reduced
      form. Libraries of mutant scFvs were tethered onto the inner membrane of dsbA
      cells and mutants that could bind fluorescently labeled antigen in the reducing
      periplasm were screened by Anchored Periplasmic Expression (APEx; Harvey et al.,
      Proc Natl Acad Sci USA 2004;101:9193-9198.). Using this approach, we isolated
      scFv antibody variants that are fully active when expressed in the cytoplasm or
      when the four Cys residues that normally form disulfides are substituted by Ser
      residues.

PMID- 19177560
TI  - Investigating protein unfolding kinetics by pulse proteolysis.
AB  - Investigation of protein unfolding kinetics of proteins in crude samples may
      provide many exciting opportunities to study protein energetics under
      unconventional conditions. As an effort to develop a method with this capability,
      we employed "pulse proteolysis" to investigate protein unfolding kinetics. Pulse
      proteolysis has been shown to be an effective and facile method to determine
      global stability of proteins by exploiting the difference in proteolytic
      susceptibilities between folded and unfolded proteins. Electrophoretic separation
      after proteolysis allows monitoring protein unfolding without protein
      purification. We employed pulse proteolysis to determine unfolding kinetics of E.
      coli maltose binding protein (MBP) and E. coli ribonuclease H (RNase H). The
      unfolding kinetic constants determined by pulse proteolysis are in good agreement
      with those determined by circular dichroism. We then determined an unfolding
      kinetic constant of overexpressed MBP in a cell lysate. An accurate unfolding
      kinetic constant was successfully determined with the unpurified MBP. Also, we
      investigated the effect of ligand binding on unfolding kinetics of MBP using
      pulse proteolysis. On the basis of a kinetic model for unfolding of MBP*maltose
      complex, we have determined the dissociation equilibrium constant (K(d)) of the
      complex from unfolding kinetic constants, which is also in good agreement with
      known K(d) values of the complex. These results clearly demonstrate the
      feasibility and the accuracy of pulse proteolysis as a quantitative probe to
      investigate protein unfolding kinetics.

PMID- 19177561
TI  - Discovery of amyloid-beta aggregation inhibitors using an engineered assay for
      intracellular protein folding and solubility.
AB  - Genetic and biochemical studies suggest that Alzheimer's disease (AD) is caused
      by a series of events initiated by the production and subsequent aggregation of
      the Alzheimer's amyloid beta peptide (Abeta), the so-called amyloid cascade
      hypothesis. Thus, a logical approach to treating AD is the development of small
      molecule inhibitors that either block the proteases that generate Abeta from its
      precursor (beta- and gamma-secretases) or interrupt and/or reverse Abeta
      aggregation. To identify potent inhibitors of Abeta aggregation, we have
      developed a high-throughput screen based on an earlier selection that effectively
      paired the folding quality control feature of the Escherichia coli Tat protein
      export system with aggregation of the 42-residue AD pathogenesis effecter
      Abeta42. Specifically, a tripartite fusion between the Tat-dependent export
      signal ssTorA, the Abeta42 peptide and the beta-lactamase (Bla) reporter enzyme
      was found to be export incompetent due to aggregation of the Abeta42 moiety.
      Here, we reasoned that small, cell-permeable molecules that inhibited Abeta42
      aggregation would render the ssTorA-Abeta42-Bla chimera competent for Tat export
      to the periplasm where Bla is active against beta-lactam antibiotics such as
      ampicillin. Using a fluorescence-based version of our assay, we screened a
      library of triazine derivatives and isolated four nontoxic, cell-permeable
      compounds that promoted efficient Tat-dependent export of ssTorA-Abeta42-Bla.
      Each of these was subsequently shown to be a bona fide inhibitor of Abeta42
      aggregation using a standard thioflavin T fibrillization assay, thereby
      highlighting the utility of our bacterial assay as a useful screen for
      antiaggregation factors under physiological conditions.

PMID- 19177563
TI  - Insights into defibrotide as therapy for veno-occlusive disease.

PMID- 19177562
TI  - Walker-A threonine couples nucleotide occupancy with the chaperone activity of
      the AAA+ ATPase ClpB.
AB  - Hexameric AAA+ ATPases induce conformational changes in a variety of
      macromolecules. AAA+ structures contain the nucleotide-binding P-loop with the
      Walker A sequence motif: GxxGxGK(T/S). A subfamily of AAA+ sequences contains Asn
      in the Walker A motif instead of Thr or Ser. This noncanonical subfamily includes
      torsinA, an ER protein linked to human dystonia and DnaC, a bacterial helicase
      loader. Role of the noncanonical Walker A motif in the functionality of AAA+
      ATPases has not been explored yet. To determine functional effects of
      introduction of Asn into the Walker A sequence, we replaced the Walker-A Thr with
      Asn in ClpB, a bacterial AAA+ chaperone which reactivates aggregated proteins. We
      found that the T-to-N mutation in Walker A partially inhibited the ATPase
      activity of ClpB, but did not affect the ClpB capability to associate into
      hexamers. Interestingly, the noncanonical Walker A sequence in ClpB induced
      preferential binding of ADP vs. ATP and uncoupled the linkage between the ATP
      bound conformation and the high-affinity binding to protein aggregates. As a
      consequence, ClpB with the noncanonical Walker A sequence showed a low chaperone
      activity in vitro and in vivo. Our results demonstrate a novel role of the Walker
      A Thr in sensing the nucleotide's gamma-phosphate and in maintaining an
      allosteric linkage between the P-loop and the aggregate binding site of ClpB. We
      postulate that AAA+ ATPases with the noncanonical Walker A might utilize distinct
      mechanisms to couple the ATPase cycle with their substrate-remodeling activity.

PMID- 19177564
TI  - Kupffer cells and hepatocyte metabolism: a two-way street?

PMID- 19177565
TI  - The genes that underlie fatty liver disease: the harvest has begun.

PMID- 19177566
TI  - Jaundice developing in a patient with hepatitis C4 months after liver
      transplantation.

PMID- 19177568
TI  - Liver disease as a risk factor for cognitive decline and dementia: an under
      recognized issue.

PMID- 19177570
TI  - In vitro-targeted gene identification in patients with hepatitis C using a genome
      wide microarray technology.
AB  - Iron in association with reactive oxygen species (ROS) is highly toxic,
      aggravating oxidative stress reactions. Increased iron not only plays an
      important role in the progression of hereditary hemochromatosis (HH) but also in
      common liver diseases such as chronic hepatitis C. The underlying mechanisms of
      hepatitis C virus (HCV)-mediated iron accumulation, however, are poorly
      understood. We introduce an in vitro-targeted approach to identify ROS/iron
      regulated genes in patients with HCV using a genome-wide DNA microarray. The
      sensitivity of the 32,231 complementary DNA clone-carrying microarray was
      approximately 20% as estimated by detecting target genes of the genome-wide
      transcription factor hypoxia inducible factor 1alpha. Upon in vitro challenge to
      iron and oxidative stress, 265 iron-related and 1326 ROS-related genes could be
      identified in HepG2 cells; 233 significantly regulated genes were found in
      patients with mild (HCV) or severe (HH) iron deposition. Notably, 17 of the in
      vitro-selected genes corresponded to the genes identified in patients with HCV or
      HH. Among them, natriuretic peptide precursor B (NPPB) was the only iron
      regulated gene identified in vitro that was differentially regulated between HCV
      and HH. Reverse-transcription polymerase chain reaction confirmed most of the
      microarray-identified genes in an even larger group of patients (n = 12). In
      patients with HCV, these included genes that are associated with RNA processing
      (MED9/NFAT, NSUN2), proliferation, differentiation, hypoxia, or iron metabolism
      (ISG20, MIG6, HIG2, CA9, NDRG1), whereas none of the nine known iron-related
      genes showed significant differences between HCV and HH. CONCLUSION: Although
      high-density microarray technology is less suitable for routine liver diagnosis,
      its use in combination with prior in vitro selection is a powerful approach to
      identify candidate genes relevant for liver disease.

PMID- 19177571
TI  - Serum hyaluronic acid with serum ferritin accurately predicts cirrhosis and
      reduces the need for liver biopsy in C282Y hemochromatosis.
AB  - Diagnosing the presence of cirrhosis is crucial for the management of patients
      with C282Y hereditary hemochromatosis (HH). HH patients with serum ferritin
      >1,000 microg/L are at risk of cirrhosis; however, the majority of these patients
      do not have cirrhosis. Noninvasive markers of hepatic fibrosis may assist in
      determining which patients with a serum ferritin >1,000 microg/L have cirrhosis
      and require liver biopsy. This study evaluated the utility of current diagnostic
      algorithms for detecting cirrhosis, including serum ferritin concentration,
      platelet counts, and aspartate aminotransferase (AST) levels, in combination with
      serum markers of fibrosis, hyaluronic acid and collagen type IV (CLIV), in
      predicting cirrhosis in HH patients. Stage of fibrosis, serum hyaluronic acid and
      CLIV levels, were measured in 56 patients with HH. No patient with a serum
      ferritin <1,000 microg/L had cirrhosis, but only 40% of patients with serum
      ferritin >1,000 microg/L were cirrhotic. A combination of platelet count (<200 x
      10(9)/L), elevated AST, and serum ferritin >1,000 microg/L did not detect 30% of
      cirrhotic subjects. Serum hyaluronic acid was increased in HH compared with
      controls (42.0 +/- 9.8 ng/mL versus 19.3 +/- 1.8 ng/mL; P = 0.02). A hyaluronic
      acid concentration >46.5 ng/mL was 100% sensitive and 100% specific in
      identifying patients with cirrhosis. In patients with serum ferritin >1,000
      microg/L, hyaluronic acid levels were significantly elevated in patients with
      cirrhosis versus those without cirrhosis (137 +/- 34.4 ng/mL versus 18.6 +/- 1.5
      ng/mL, respectively; P = 0.006). CLIV >113 ng/mL was 100% sensitive but only 56%
      specific for cirrhosis (area under the curve = 0.78; P = 0.01). CONCLUSION: In
      HH, the measurement of hyaluronic acid in patients with serum ferritin >1,000
      microg/L is a noninvasive, accurate, and cost-effective method for the diagnosis
      of cirrhosis. (HEPATOLOGY 2009;49:418-425.).

PMID- 19177572
TI  - Structural insight into the catalytic mechanism of gluconate 5-dehydrogenase from
      Streptococcus suis: Crystal structures of the substrate-free and quaternary
      complex enzymes.
AB  - Gluconate 5-dehydrogenase (Ga5DH) is an NADP(H)-dependent enzyme that catalyzes a
      reversible oxidoreduction reaction between D-gluconate and 5-keto-D-gluconate,
      thereby regulating the flux of this important carbon and energy source in
      bacteria. Despite the considerable amount of physiological and biochemical
      knowledge of Ga5DH, there is little physical or structural information available
      for this enzyme. To this end, we herein report the crystal structures of Ga5DH
      from pathogenic Streptococcus suis serotype 2 in both substrate-free and liganded
      (NADP(+)/D-gluconate/metal ion) quaternary complex forms at 2.0 A resolution.
      Structural analysis reveals that Ga5DH adopts a protein fold similar to that
      found in members of the short chain dehydrogenase/reductase (SDR) family, while
      the enzyme itself represents a previously uncharacterized member of this family.
      In solution, Ga5DH exists as a tetramer that comprised four identical
      approximately 29 kDa subunits. The catalytic site of Ga5DH shows considerable
      architectural similarity to that found in other enzymes of the SDR family, but
      the S. suis protein contains an additional residue (Arg104) that plays an
      important role in the binding and orientation of substrate. The quaternary
      complex structure provides the first clear crystallographic evidence for the role
      of a catalytically important serine residue and also reveals an amino acid tetrad
      RSYK that differs from the SYK triad found in the majority of SDR enzymes.
      Detailed analysis of the crystal structures reveals important contributions of
      Ca(2+) ions to active site formation and of specific residues at the C-termini of
      subunits to tetramer assembly. Because Ga5DH is a potential target for therapy,
      our findings provide insight not only of catalytic mechanism, but also suggest a
      target of structure-based drug design.

PMID- 19177573
TI  - Crystal structure of domain-swapped STE20 OSR1 kinase domain.
AB  - OSR1 (oxidative stress-responsive-1) and SPAK (Ste20/Sps1-related proline/alanine
      rich kinase) belong to the GCK-VI subfamily of Ste20 group kinases. OSR1 and SPAK
      are key regulators of NKCCs (Na(+)/K(+)/2Cl(-) cotransporters) and activated by
      WNK family members (with-no-lysine kinase), mutations of which are known to cause
      Gordon syndrome, an autosomal dominant form of inherited hypertension. The
      crystal structure of OSR1 kinase domain has been solved at 2.25 A. OSR1 forms a
      domain-swapped dimer in an inactive conformation, in which P+1 loop and alphaEF
      helix are swapped between dimer-related monomers. Structural alignment with
      nonswapped Ste20 TAO2 kinase indicates that the integrity of chemical
      interactions in the kinase domain is well preserved in the domain-swapped
      interfaces. The OSR1 kinase domain has now been added to a growing list of domain
      swapped protein kinases recently reported, suggesting that the domain-swapping
      event provides an additional layer of complexity in regulating protein kinase
      activity.

PMID- 19177574
TI  - Design of a heterotetrameric coiled coil.
AB  - We have successfully designed a simple peptide sequence that forms highly stable
      coiled-coil heterotetramers. Our model system is based on the GCN4-pLI parallel
      coiled-coil tetramer, first described by Kim and coworkers (Harbury et al.,
      Science 1993;262:1401-1407). We introduced glutamates at all of the e and c
      heptad positions of one sequence (ecE) and lysines at the same positions in a
      second sequence (ecK). Based on a modeling study, these sidechains are close
      enough in space to form structure-stabilizing salt bridges. We show that ecE and
      ecK are highly unstable by themselves but form very stable parallel helical
      tetramers when mixed, as judged by circular dichroism, analytical
      ultracentrifugation, and disulfide crosslinking studies. The origin of the
      difference in stabilities between the homomeric structures and the heteromeric
      structures comes from a combination of the relief of electrostatic repulsions
      with concomitant formation of electrostatic attractive interactions based on pH
      and NaCl screening experiments. We quantify the stability of the heterotetrameric
      coiled coil from a thermodynamic analysis and compare the finding to other
      similar coiled-coil systems.

PMID- 19177575
TI  - The interleukin-17 pathway is involved in human alcoholic liver disease.
AB  - Immune dysregulations in alcoholic liver diseases are still unclear, especially
      regarding alcoholic hepatitis inflammatory burst. Interleukin-17 (IL-17) is known
      to enhance neutrophil recruitment. We studied the IL-17 pathway in alcoholic
      cirrhosis and alcoholic hepatitis. Patients with alcoholic liver disease were
      compared with patients with chronic hepatitis C virus (HCV) infection or
      autoimmune liver disease and with healthy controls. IL-17 plasma levels and
      peripheral blood mononuclear cell secretion were assessed by enzyme-linked
      immunosorbent assay (ELISA) and T cell phenotype by flow cytometry. IL-17
      staining and co-staining with CD3 and myeloperoxidase were performed on liver
      biopsy specimens. IL-17 receptor expression was studied on liver biopsies and in
      human hepatic stellate cells as well as their response to recombinant IL-17 by
      chemotaxis assays. IL-17 plasma levels were dramatically increased in alcoholic
      liver disease patients. Peripheral blood mononuclear cells of patients with
      alcoholic liver disease produced higher amounts of IL-17, and their CD4(+) T
      lymphocytes disclosed an IL-17-secreting phenotype. In the liver, IL-17-secreting
      cells contributed to inflammatory infiltrates in alcoholic cirrhosis, and
      alcoholic hepatitis foci disclosed many IL-17(+) cells, including T lymphocytes
      and neutrophils. In alcoholic liver disease, liver IL-17(+) cells infiltrates
      correlated to model for end-stage liver disease score, and in alcoholic hepatitis
      to modified discriminant function. IL-17 receptor was expressed in alcoholic
      liver disease by hepatic stellate cells, and these cells recruited neutrophils
      after IL-17 stimulation in a dose-dependent manner through IL-8 and growth
      related oncogen alpha (GRO-alpha) secretion in vitro. CONCLUSION: Human alcoholic
      liver disease is characterized by the activation of the IL-17 pathway. In
      alcoholic hepatitis, liver infiltration with IL-17-secreting cell infiltrates is
      a key feature that might contribute to liver neutrophil recruitment. (Clinical
      trials number NCT00610597).

PMID- 19177576
TI  - Pathologic diagnosis of early hepatocellular carcinoma: a report of the
      international consensus group for hepatocellular neoplasia.

PMID- 19177579
TI  - Treatment of patients infected with chronic hepatitis C genotype 2 and 3: more
      data, more questions?

PMID- 19177577
TI  - Chemokines in the immunopathogenesis of hepatitis C infection.
AB  - Chronic infection with the hepatitis C virus, a noncytopathic hepatotropic RNA
      virus, affects over 170 million people worldwide. In the majority of cases,
      neither the early innate immune response nor the later adaptive immune response
      succeeds in clearing the virus, and the infection becomes chronic. Furthermore,
      in many patients, the ineffective inflammatory response drives fibrogenesis and
      the development of cirrhosis. It is critical to understand this immune pathology
      if preventative and curative therapies are to be developed. Chemokines are a
      superfamily of small proteins that promote leukocyte migration and orchestrate
      the immune response to viruses, including hepatitis C virus. Chemokines are
      crucial for viral elimination, but inappropriate persistence of expression in
      chronic hepatitis C infection can drive tissue damage and inflammation. Here we
      review the role of chemokines and their receptors in hepatitis C virus infection.

PMID- 19177580
TI  - Burning hepatic fat: therapeutic potential for liver-specific thyromimetics in
      the treatment of nonalcoholic fatty liver disease.

PMID- 19177581
TI  - Hepatitis B virus viral load and treatment decision.

PMID- 19177582
TI  - Revisiting the treatment recommendations for chronic hepatitis B.

PMID- 19177583
TI  - Do guidelines preclude hepatitis B patients from receiving treatment?

PMID- 19177585
TI  - The optimal ribavirin dose for patients infected with hepatitis C virus genotype
      3: should we utilize more?

PMID- 19177587
TI  - Hepatitis B e antigen-negative patients with persistently normal alanine
      aminotransferase levels and hepatitis B virus DNA > 2000 IU/mL.

PMID- 19177589
TI  - Blocking the hedgehog pathway inhibits hepatoblastoma growth.
AB  - Recent evidence has indicated that Hedgehog (Hh) signaling significantly
      contributes to liver development and regeneration and that activation of the
      pathway may contribute to growth of hepatocellular carcinoma (HCC) in adults.
      However, the role of Hh signaling in pediatric liver tumors remains to be
      elucidated. In this study, we show that Hh signaling is activated in
      hepatoblastoma (HB), the most common liver tumor in childhood, with most
      occurrences before the age of 3 years. The Hh target genes glioma-associated
      oncogene homolog 1 (GLI1) and Patched (PTCH1) showed increased transcript levels
      in 65% and 30% of HB samples, respectively, compared with normal liver tissues.
      Most interestingly, the gene encoding the hedgehog interacting protein (HHIP) is
      transcriptionally silenced by cytosine-phospho-guanosine (CpG) island promoter
      hypermethylation in 26% of HB cases and treatment with the DNA-demethylating
      agent 5-aza-2'-deoxycytidine partially restored HHIP expression. Blocking Hh
      signaling with the antagonist cyclopamine had a strong inhibitory effect on cell
      proliferation of HB cell lines with an activated pathway. We further demonstrate
      that this decrease in cell viability is caused by a massive induction of
      apoptosis, as shown by morphological changes and phosphatidylserine membrane
      asymmetry. In cyclopamine-exposed HB cells, caspase 3 and poly(adenosine
      diphosphate-ribose) polymerase proteins were specifically activated by their
      proteolytic cleavage. CONCLUSION: This study demonstrates, for the first time,
      the frequent occurrence of GLI1 and PTCH1 overexpression and HHIP promoter
      methylation in early childhood HB, thus indicating a key role for Hh signaling
      activation in the malignant transformation of embryonal liver cells.

PMID- 19177591
TI  - Evidence for LKB1/AMP-activated protein kinase/ endothelial nitric oxide synthase
      cascade regulated by hepatocyte growth factor, S-adenosylmethionine, and nitric
      oxide in hepatocyte proliferation.
AB  - S-adenosylmethionine (SAMe) is involved in numerous complex hepatic processes
      such as hepatocyte proliferation, death, inflammatory responses, and antioxidant
      defense. One of the most relevant actions of SAMe is the inhibition of hepatocyte
      proliferation during liver regeneration. In hepatocytes, SAMe regulates the
      levels of cytoplasmic HuR, an RNA-binding protein that increases the half-life of
      target messenger RNAs such as cyclin D1 and A2 via inhibition of hepatocyte
      growth factor (HGF)-mediated adenosine monophosphate-activated protein kinase
      (AMPK) phosphorylation. Because AMPK is activated by the tumor suppressor kinase
      LKB1, and AMPK activates endothelial nitric oxide (NO) synthase (eNOS), and NO
      synthesis is of great importance for hepatocyte proliferation, we hypothesized
      that in hepatocytes HGF may induce the phosphorylation of LKB1, AMPK, and eNOS
      through a process regulated by SAMe, and that this cascade might be crucial for
      hepatocyte growth. We demonstrate that the proliferative response of hepatocytes
      involves eNOS phosphorylation via HGF-mediated LKB1 and AMPK phosphorylation, and
      that this process is regulated by SAMe and NO. We also show that knockdown of
      LKB1, AMPK, or eNOS with specific interference RNA (iRNA) inhibits HGF-mediated
      hepatocyte proliferation. Finally, we found that the LKB1/AMPK/eNOS cascade is
      activated during liver regeneration after partial hepatectomy and that this
      process is impaired in mice treated with SAMe before hepatectomy, in knockout
      mice deficient in hepatic SAMe, and in eNOS knockout mice. CONCLUSION: We have
      identified an LKB1/AMPK/eNOS cascade regulated by HGF, SAMe, and NO that
      functions as a critical determinant of hepatocyte proliferation during liver
      regeneration after partial hepatectomy.

PMID- 19177592
TI  - Hepatitis C virus persisting after clinically apparent sustained virological
      response to antiviral therapy retains infectivity in vitro.
AB  - Hepatitis C virus (HCV) can persist in the liver, lymphoid cells, and serum of
      individuals with apparently complete spontaneous or therapy-induced resolution of
      hepatitis C and can replicate in vivo and in vitro in human T cells. The current
      study was aimed at assessing the infectivity of HCV persisting at very low levels
      using the previously established HCV infection system in human T cells. Naive
      lymphoid cells were exposed to plasma and/or supernatants from cultured
      peripheral blood mononuclear cells from nine individuals with apparent sustained
      virological response after completion of antiviral therapy. Exposed cells were
      analyzed for HCV RNA-positive and HCV RNA-negative strands and, in selected
      cases, for HCV nonstructural protein 5a (NS5a), the appearance of HCV variants,
      and the release of virions by immunoelectron microscopy (IEM). The results showed
      that 11 of the 12 established cultures became HCV RNA-positive strand-reactive,
      whereas 4 also expressed the virus replicative strand. NS5a protein was detected
      in the de novo infected cells, and clonal sequencing revealed HCV variants not
      found in inocula. IEM demonstrated enveloped HCV particles in plasma used as
      inocula and in culture supernatant from T cells exposed to that plasma. Overall,
      HCV carried in three of the nine individuals studied elicited productive
      infection in vitro. CONCLUSION: HCV persisting at very low levels long after
      therapy-induced resolution of chronic hepatitis C can remain infectious. The
      retained biological competence of the virus might have implications with respect
      to the mechanisms of its persistence and the epidemiology of HCV infection.

PMID- 19177593
TI  - Multiple division cycles and long-term survival of hepatocytes are distinctly
      regulated by extracellular signal-regulated kinases ERK1 and ERK2.
AB  - We investigated the specific role of the mitogen-activated protein kinase (MAPK)
      extracellular signal-regulated kinase 1 (ERK1)/ERK2 pathway in the regulation of
      multiple cell cycles and long-term survival of normal hepatocytes. An early and
      sustained epidermal growth factor (EGF)-dependent MAPK activation greatly
      improved the potential of cell proliferation. In this condition, almost 100% of
      the hepatocytes proliferated, and targeting ERK1 or ERK2 via RNA interference
      revealed the specific involvement of ERK2 in this regulation. However, once their
      first cell cycle was performed, hepatocytes failed to undergo a second round of
      replication and stayed blocked in G1 phase. We demonstrated that sustained EGF
      dependent activation of the MAPK/ERK kinase (MEK)/ERK pathway was involved in
      this blockage as specific transient inhibition of the cascade repotentiated
      hepatocytes to perform a new wave of replication and multiple cell cycles. We
      identified this mechanism by showing that this blockage was in part supported by
      ERK2-dependent p21 expression. Moreover, continuous MEK inhibition was associated
      with a lower apoptotic engagement, leading to an improvement of survival up to 3
      weeks. Using RNA interference and ERK1 knockout mice, we extended these results
      by showing that this improved survival was due to the specific inhibition of ERK1
      expression/phosphorylation and did not involve ERK2. CONCLUSION: Our results
      emphasize that transient MAPK inhibition allows multiple cell cycles in primary
      cultures of hepatocytes and that ERK2 has a key role in the regulation of S phase
      entry. Moreover, we revealed a major and distinct role of ERK1 in the regulation
      of hepatocyte survival. Taken together, our results represent an important
      advance in understanding long-term survival and cell cycle regulation of
      hepatocytes.

PMID- 19177594
TI  - NKG2D-retinoic acid early inducible-1 recognition between natural killer cells
      and Kupffer cells in a novel murine natural killer cell-dependent fulminant
      hepatitis.
AB  - Increasing evidence suggests the contribution of natural killer (NK) cells to
      pathogenesis of human hepatitis, but the detailed mechanisms have yet to be
      clearly elucidated. In this study, injection of polyinosinic:polycytidylic acid
      (poly I:C) and D-galactosamine (D-GalN) was used to establish a novel murine
      fulminant hepatitis model: results showed that predepletion of either NK cells or
      Kupffer cells could completely abolish the liver injury. Injection of poly I:C/D
      GalN into mice could promote tumor necrosis factor-alpha production and surface
      retinoic acid early inducible-1 (Rae1) protein expression by Kupffer cells, which
      then activated NK cells to produce interferon-gamma via NKG2D-Rae1 recognition.
      NK cell-derived interferon-gamma and Kupffer cell-derived tumor necrosis factor
      alpha synergistically mediated the severe liver injury. Moreover, Kupffer cell
      derived interleukin-12 and interleukin-18 were also found to improve cross talk
      between NK cells and Kupffer cells. CONCLUSION: These results provide the first
      in vivo evidence that NKG2D/ligand interaction is involved in the synergic
      effects of NK cells and Kupffer cells on acute liver injury.

PMID- 19177595
TI  - Blockade of four-transmembrane L6 family member 5 (TM4SF5)-mediated
      tumorigenicity in hepatocytes by a synthetic chalcone derivative.
AB  - We previously reported that the four-transmembrane L6 family member 5 (TM4SF5)
      was highly expressed in hepatocarcinoma, induced morphological elongation and
      epithelial-mesenchymal transition, and caused abnormal cell growth in multilayers
      in vitro and tumor formation in vivo. In this study, we identified a synthetic
      compound, 4'-(p-toluenesulfonylamido)-4-hydroxychalcone (TSAHC) that antagonized
      both the TM4SF5-mediated multilayer growth and TM4SF5-enhanced
      migration/invasion. TSAHC treatment induced multilayer-growing cells to grow in
      monolayers, recovering contact inhibition without accompanying apoptosis, and
      inhibited chemotactic migration and invasion. Tumor formation in nude mice
      injected with TM4SF5-expressing cells and the growth of cells expressing
      endogenous TM4SF5, but not of TM4SF5-null cells, was suppressed by treatment with
      TSAHC, but not by treatment with its analogs. The structure-activity relationship
      indicated the significance of 4'-p-toluenesulfonylamido and 4-hydroxy groups for
      the anti-TM4SF5 effects of TSAHC. Point mutations of the putative N-glycosylation
      sites abolished the TM4SF5-specific TSAHC responsiveness. CONCLUSION: These
      observations suggest that TM4SF5-enhanced tumorigenic proliferation and
      metastatic potential can be blocked by TSAHC, likely through targeting the
      extracellular region of TM4SF5, which is important for protein-protein
      interactions.

PMID- 19177596
TI  - Abrogation of hepatic ATP-citrate lyase protects against fatty liver and
      ameliorates hyperglycemia in leptin receptor-deficient mice.
AB  - Hepatic steatosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and a
      key component of obesity-associated metabolic dysfunctions featuring
      dyslipidemia, insulin resistance, and loss of glycemic control. It has yet to be
      completely understood how much dysregulated de novo lipogenesis contributes to
      the pathogenic development of hepatic steatosis and insulin resistance. ATP
      citrate lyase (ACL) is a lipogenic enzyme that catalyzes the critical reaction
      linking cellular glucose catabolism and lipogenesis, converting cytosolic citrate
      to acetyl-coenzyme A (CoA). Acetyl-CoA is further converted to malonyl-CoA, the
      essential precursor for fatty acid biosynthesis. We investigated whether
      dysregulation of hepatic ACL is metabolically connected to hepatic steatosis,
      insulin resistance, and hyperglycemia. We found that in leptin receptor-deficient
      db/db mice, the expression of ACL was selectively elevated in the liver but not
      in the white adipose tissue. Liver-specific ACL abrogation via adenovirus
      mediated RNA interference prominently reduced the hepatic contents of both acetyl
      CoA and malonyl-CoA, markedly inhibited hepatic de novo lipogenesis, and
      protected against hepatic steatosis in db/db mice. Surprisingly, liver-specific
      ACL abrogation markedly inhibited the expression of peroxisome proliferator
      activated receptor-gamma and the entire lipogenic program in the liver. Moreover,
      hepatic ACL deficiency resulted in significantly down-regulated expression of
      gluconeogenic genes in the liver as well as enhanced insulin sensitivity in the
      muscle, leading to substantially improved systemic glucose metabolism.
      CONCLUSION: These findings establish a crucial role of hepatic ACL in lipid and
      glucose metabolism; therefore, hepatic ACL may serve as a potential target to
      treat NAFLD and type 2 diabetes.

PMID- 19177597
TI  - Jean-Pierre Benhamou, a tribute (July 13, 1927 to September 17, 2008).

PMID- 19177598
TI  - Detection of novel biomarkers of liver cirrhosis by proteomic analysis.
AB  - Hepatic cirrhosis is a life-threatening disease arising from different chronic
      liver disorders. One major cause for hepatic cirrhosis is chronic hepatitis C.
      Chronic hepatitis C is characterized by a highly variable clinical course, with
      at least 20% developing liver cirrhosis within 40 years. Only liver biopsy allows
      a reliable evaluation of the course of hepatitis C by grading inflammation and
      staging fibrosis, and thus serum biomarkers for hepatic fibrosis with high
      sensitivity and specificity are needed. To identify new candidate biomarkers for
      hepatic fibrosis, we performed a proteomic approach of microdissected cirrhotic
      septa and liver parenchyma cells. In cirrhotic septa, we detected an increasing
      expression of cell structure associated proteins, including actin, prolyl 4
      hydroxylase, tropomyosin, calponin, transgelin, and human microfibril-associated
      protein 4 (MFAP-4). Tropomyosin, calponin, and transgelin reflect a contribution
      of activated stellate cells/myofibroblasts to chronic liver injury. The
      expression of tropomyosin, transgelin, and MFAP-4, an extracellular matrix
      associated protein, were further evaluated by immunohistochemistry. Tropomyosin
      and MFAP-4 demonstrated high serum levels in patients with hepatic cirrhosis of
      different causes. CONCLUSION: A quantitative analysis of MFAP-4 serum levels in a
      large number of patients showed MFAP-4 as novel candidate biomarker with high
      diagnostic accuracy for prediction of nondiseased liver versus cirrhosis [area
      under receiver operating characteristic curve (AUC) = 0.97, P < 0.0001] as well
      as stage 0 versus stage 4 fibrosis (AUC = 0.84, P < 0.0001), and stages 0 to 3
      versus stage 4 fibrosis (AUC = 0.76, P < 0.0001).

PMID- 19177600
TI  - Old problems still mar fight against ancient disease.

PMID- 19177599
TI  - Heartwatch: a secondary prevention programme in primary  care in Ireland.
AB  - BACKGROUND: Heartwatch, a secondary prevention programme in primary care was
      initiated in 2003, based on the second European Joint Task Force recommendations
      for secondary prevention of coronary heart disease (CHD). The aim was to examine
      the effect of the first 2 years of the Heartwatch programme on cardiovascular
      risk factors and treatments. DESIGN: Prospective cohort study of patients with
      established CHD enrolled into the Heartwatch programme. METHODS: Four hundred and
      seventy (20%) general practitioners nationwide participated in the programme,
      recruiting 11,542 patients with established CHD (earlier myocardial infarction,
      coronary intervention or coronary artery bypass surgery). Clinical data were
      electronically transferred by each general practitioner to a central database.
      Comparison of changes in risk factors and treatments at 1-year and 2-year follow
      up from baseline were made using paired t-test for continuous and McNemar's test
      for categorical data. RESULTS: Statistically significant changes in systolic
      blood pressure, diastolic blood pressure, total and low-density lipoprotien
      cholesterol and smoking status at 1 and 2 years (P <0.0001) were observed. Little
      or no improvements were shown for exercise, BMI or waist circumference. Increases
      in the prescribing of statins, angiotensin-converting enzyme inhibitors and beta
      blockers over the course of the study were observed. CONCLUSION: The Heartwatch
      programme has demonstrated significant improvements in the main risk factors and
      treatments for CHD. More effective interventions are required to reduce BMI,
      waist circumference and physical inactivity in this population. The increases in
      treatment uptake are approaching the optimal levels in this population.

PMID- 19177601
TI  - Retraction notice to "Colon-specific, mutual azo prodrug of 5-aminosalicylic acid
      with L-tryptophan: synthesis, kinetic studies and evaluation of its mitigating
      effect in trinitrobenzenesulfonic acid-induced colitis in rats" [Bioorg. Med.
      Chem. 17 (2007) 15 (2007) 4903-4909].

PMID- 19177602
TI  - Comparison of cardioprotective effects of salvianolic acid B and benazepril on
      large myocardial infarction in rats.

PMID- 19177603
TI  - Proceedings of the 14th International Meeting of the Leksell Gamma Knife Society,
      May 2008, Quebec City, Canada.

PMID- 19177604
TI  - Proceedings of the 5th Conference of the International CoQ10 Association,
      November 9-12, 2007, Kobe, Japan.

PMID- 19177605
TI  - Proceedings of the 8th International Bode Hygiene Days, 14-17 June 2007, Tallinn,
      Estonia.

PMID- 19177606
TI  - Proceedings of the 12th Triennial Heartworm Symposium 2007.

PMID- 19177607
TI  - [Regulation of biofilm formation in Escherichia coli K12: effect of mutations in
      HNS, StpA, lon, and rpoN genes].
AB  - More than 99% of bacteria exist in natural ecosystems as specifically organized
      biofilms adhering to solid surfaces. Biofilms have a typical architecture and are
      enclosed in exopolymeric matrix. Bacteria living in biofilms are extremely
      resistant to antibacterial factors. In this work we studied the role of some
      global regulators of gene expression on biofilm formation by Escherichia coli
      K12. The Histone-like proteins H-NS and StpA were shown to play an essential role
      in the regulation of biofilm formation. Mutant strains deficient in HNS or StpA
      had lower levels of biofilm formation than the wild-type isogenic strain. A
      double mutant deficient in the two proteins was virtually incapable of forming
      the biofilms. The mutations in the rpoN gene encoding for the sigma N subunit of
      RNA-polymerase and in lon gene encoding for Lon-proteinase induced a 40-60%
      increase in the biofilm formation.

PMID- 19177608
TI  - [A system for heart rate stabilization during veloergometric exercise].

PMID- 19177609
TI  - [Automated detection of artifacts in electroencephalographic signal].

PMID- 19177610
TI  - [Calculation of the X-ray bremsstrahlung transmission coefficient of test
      filter].

PMID- 19177611
TI  - [Simulation of the mass transfer in a hemodialyzer].

PMID- 19177612
TI  - [Excitation of optokinetic nystagmus and measurement of its characteristics using
      computer videotechnologies].

PMID- 19177613
TI  - [A hardware-software system for diagnosis of venous thrombembolic complications].

PMID- 19177614
TI  - [Improvement of the blood banking safety system for medical personnel].

PMID- 19177615
TI  - Nowhere to run... and nowhere to hide from bigger financial problems facing the
      industry, critics say, despite decrease in spending growth.
AB  - While the latest numbers say the growth in healthcare spending is slowing,
      industry executives don't see much reason to celebrate. "Rising healthcare costs
      put pressure on states in the form of increased Medicaid costs, it puts pressure
      on the federal budget ... and it puts pressure on taxpayers ... while facing ever
      rising costs for private healthcare."

PMID- 19177616
TI  - Chronic diseases up in U.S. Study shows rise in incidence and cost over 10 years.

PMID- 19177617
TI  - As Obama seeks stimulus... some wonder where the funds will be going.

PMID- 19177618
TI  - Daschle's warm reception. Industry leaders like what HHS nominee has to say.

PMID- 19177619
TI  - CMS: support lackin. Others disagree on disease management findings.

PMID- 19177620
TI  - Objection? Sustained. With costs continuing to rise, it's time re-evaluate
      business as usual.

PMID- 19177621
TI  - Parity pays dividends. Increased costs in behavioral-health benefits offset by
      other savings.

PMID- 19177622
TI  - View from Washington: this time, they mean it.

PMID- 19177623
TI  - They are cancer sticks. The medical experts link smoking and lung disease.

PMID- 19177624
TI  - Heats of formation and bond energies of the H(3-n)BX(n) compounds for (X = F, Cl,
      Br, I, NH2, OH, and SH).
AB  - Atomization energies at 0 K and heats of formation at 0 and 298 K are predicted
      for the borane compounds H(3-n)BX(n) for (X = F, Cl, Br, I, NH2, OH, and SH) and
      various radicals from coupled cluster theory (CCSD(T)) calculations with an
      effective core potential correlation-consistent basis set for I. In order to
      achieve near chemical accuracy (+/-1.5 kcal/mol), three corrections were added to
      the complete basis set binding energies calculated from frozen core coupled
      cluster theory energies: a correction for core-valence effects, a correction for
      scalar relativistic effects, and a correction for first-order atomic spin-orbit
      effects. Vibrational zero point energies were computed at the MP2 level. The
      calculated heats of formation are in excellent agreement with the available
      experimental data for the closed shell molecules, but show larger differences
      with the reported "experimental" values for the BX2 radicals. The heats of
      formation of the BX2 radicals were also calculated at the G3(MP2) level of
      theory, and the values were in excellent agreement with the more accurate CCSD(T)
      values. On the basis of extensive comparisons with experiment for a wide range of
      compounds, our calculated values for these radicals should be good to +/-1.5
      kcal/mol and thus are to be preferred over the experimental values. The
      accurately calculated heats of formation allow us to predict the B-X and B-H
      adiabatic bond dissociation energies (BDEs) to within +/-1.5 kcal/mol. The B-F
      BDEs in the H(3-n)BF(n) compounds and in BF (1Sigma+) are the largest BDEs in
      comparison to the other substituents that were investigated. The second and third
      largest B-X BDEs in the H(3-n)BX(n) and BX compounds are predicted for X = OH and
      NH2, respectively. The substituents have a minimal effect on the B-H BDEs in HBX2
      and H2BX compared to the first B-H BDE of borane. The differences in adiabatic
      and diabatic BDEs, which are related to the reorganization energy in the product,
      can be estimated from singlet-triplet splittings in these molecules, and can
      account for the large fluctuations in adiabatic BDEs observed, specifically for
      the BX2 and HBX radicals, during the stepwise loss of the respective
      substituents.

PMID- 19177625
TI  - Determinants of plasma interleukin-6 levels among survivors  of myocardial
      infarction.
AB  - BACKGROUND: We identify determinants of plasma interleukin-6 (IL-6) levels in a
      multicenter panel study of myocardial infarction (MI) survivors, using repeated
      measurements to evaluate both baseline and time-varying factors. DESIGN AND
      METHODS: Survivors of MI (N= 1003) recruited in six European cities had repeated
      measurements (median: 6/patient) of IL-6. At baseline, participants' behaviour
      and medical histories were determined by interview, and blood pressure,
      anthropometry, cholesterol and N-terminal B-type natriuretic peptide (NT-proBNP)
      were measured. Short-term exposures and medication intake were recorded at each
      visit. Generalized additive mixed models were used to analyze associations of IL
      6 with baseline and time-varying risk factors, taking into account repeated
      measurements. RESULTS: Age, hour of blood withdrawal, body mass index, pack-years
      of smoking, NT-proBNP, systolic blood pressure, high-density lipoprotein
      cholesterol, persistent cough/phlegm and statin use were significantly and
      independently associated with IL-6 after adjustment for city, recurrent MI,
      baseline alcohol intake, current active smoking, tea consumption and extreme
      anger or stress. CONCLUSION: Among MI survivors, IL-6 levels are associated with
      many traditional cardiovascular risk factors. Patients with elevated NT-proBNP,
      respiratory symptoms or obesity had higher IL-6 concentrations and may
      potentially be at greater risk for coronary artery disease progression.

PMID- 19177626
TI  - Prevalence and pattern of hypertension in a semiurban  community in Nigeria.
AB  - BACKGROUND: Hypertension has been reported to be a major problem of the blacks.
      There is a paucity of studies, however, on community-based surveys on the
      prevalence and pattern of hypertension in Nigeria in the recent time. This study
      sought to investigate the prevalence and pattern of hypertension in the adult
      population living in the ancient semiurban community of Ile-Ife, southwest
      Nigeria. DESIGN AND METHODS: Two thousand and ninety-seven adults of above 20
      years of age were recruited into the door-to-door survey through a multistage
      cluster sampling technique. Diagnosis of hypertension was based on blood pressure
      (BP) threshold of 160/95 mmHg and the World Health Organization /International
      Society of Hypertension guidelines (Joint National Committee on Prevention,
      Detection, Evaluation, and Treatment of High Blood Pressure guidelines)
      definitions. Resting blood pressure was taken using electronic sphygmomanometer.
      RESULTS: The mean age and BP of the participants were aged 44.2 +/- 11.6 years
      and 127/77 mmHg, respectively. The participants (36.6%) had a BP of greater than
      or equal to 140/90 mmHg whereas 13.3% had BP of greater than or equal to 160/95
      mmHg. 22.1% had isolated systolic hypertension whereas 14.5% had isolated
      diastolic hypertension using the BP of greater than or equal to 140/90 mmHg cut
      off-point. Using the BP of greater than or equal to 160/95 mmHg, isolated
      systolic hypertension and isolated diastolic hypertension were 6.63%,
      respectively. A male-to-female ratio of 1.7 : 1 and 1 : 5 was observed for BP
      greater than or equal to 140/90 mmHg and BP greater than or equal to 160/95 mmHg,
      respectively. Hypertension prevalence increased across age gradient from young to
      old adults. CONCLUSION: The prevalence estimates of hypertension obtained in this
      study was higher than those found in most earlier studies from Nigeria, other
      West Africa nations and for African-Americans.

PMID- 19177627
TI  - Cardiac surgery in patients with haemophilia.
AB  - Today the populations of haemophilia patients in many countries have a higher
      life expectancy than previously known, and age-related disorders such as arterial
      disease are expected to become more prevalent, calling for surgical intervention.
      Cardiac surgery constitutes a major haemostatic challenge because of sternotomy,
      the need of total heparinization, extracorporal circulation, mild hypothermia and
      cardiac arrest. To evaluate our current experience and results with cardiac
      surgery in patients with haemophilia the present case series report on six
      patients with haemophilia A (Severe = 1, Moderate = 1, Mild = 4) undergoing
      cardiac surgery (coronary artery bypass grafting; CABG = 2, aortic valve
      replacement = 1, CABG + aortic valve replacement = 2, ventricular resection +
      mitral valve reconstruction = 1). The present paper provides detailed information
      on the haemostatic treatment regimens adopted (factor concentrate dosages, timing
      and duration) and postoperative thromboprophylaxis (dosing and duration of low
      molecular weight heparin). Moreover, we present data on concomitant disorders
      (hypertension, hypercholesterolaemia, atrial fibrillation and diabetes), left
      ventricle ejection fraction (30-60%), type of anaesthesia, total amount of
      heparin (34 500-53 500 IU) and duration of extracorporeal circulation (80-115
      min). Clinical outcomes included: re-operation because of bleeding (none),
      transfusion requirements, peri- and postoperative blood loss and complications
      and postoperative development of inhibitors (none). Clinical outcomes were
      compared with a control group of patients (n = 5993) without haemophilia and we
      found no difference in postoperative morbidity. Adopting meticulously supervised
      haemostatic treatment regimens, we have successfully performed major cardiac
      surgery in patients with haemophilia A. The clinical outcome as well as the
      severity and incidence of postoperative complications were similar to patients
      without haemophilia.

PMID- 19177628
TI  - South Africa heads into elections in a sorry state of health.

PMID- 19177629
TI  - Caregiving: the odyssey of becoming more human.

PMID- 19177630
TI  - Colorectal cancer screening.  What's stopping you?

PMID- 19177631
TI  - More evidence links green tea to heart health.

PMID- 19177632
TI  - Old grains, new tastes.  Go beyond the ordinary.

PMID- 19177633
TI  - I've heard endorphins can help with pain control and make you feel good.  How can
      I get my body to produce endorphins?

PMID- 19177634
TI  - I've noticed spots of blood on the front of my underwear when I wake up in the
      morning.  Should I be concerned?

PMID- 19177635
TI  - Unprecedented hemiketal cembranolides with anti-inflammatory activity from the
      soft coral Lobophytum durum.
AB  - Chemical investigations of the soft coral Lobophytum durum have led to the
      isolation of three unprecedented hemiketal cembranolides, durumhemiketalolides A
      C (1-3). Full NMR spectroscopic assignments are provided for all isolated
      metabolites. The anti-inflammatory activities of 1-3 were evaluated in vitro.

PMID- 19177636
TI  - [Child abuse more common than the official statistics indicate].

PMID- 19177637
TI  - With the economy in the ICU, pressure increases on emergency departments.

PMID- 19177638
TI  - Should the digital rectal examination be a part of the trauma secondary survey?

PMID- 19177640
TI  - Driver electronic device use in 2007.

PMID- 19177639
TI  - Is subcutaneous administration of rapid-acting insulin as effective as
      intravenous insulin for treating diabetic ketoacidosis?
AB  - To determine whether intermittent subcutaneous administration of rapid-acting
      insulin is as effective as intravenous infusion of regular insulin for treating
      uncomplicated diabetic ketoacidosis, we performed a MEDLINE, EMBASE, and Cochrane
      Library search, using the key words "subcutaneous insulin AND intravenous insulin
      AND diabetic ketoacidosis; LIMIT humans and English." We also searched the
      references in these articles for additional studies. This search yielded a total
      of 35 articles, 4 of which directly addressed the question at hand. According to
      this review of the available evidence; subcutaneous administration of rapid
      acting insulin analogs such as lispro is as effective and safe as intravenous
      infusion of regular insulin for the management of uncomplicated diabetic
      ketoacidosis. In addition, use of insulin analogs may confer an overall cost
      savings, obviating the need for infusion pumps and ICU admissions in certain
      institutions. Therefore, it would be safe and effective to use subcutaneously
      administered rapid-acting insulin analogues instead of intravenous regular
      insulin infusions for patients with uncomplicated diabetic ketoacidosis.

PMID- 19177641
TI  - Subcutaneous emphysema of the upper extremity following penetrating blackthorn
      injury to the wrist.
AB  - SUMMARY: Noninfective subcutaneous emphysema of the upper extremity, albeit rare,
      has to be borne in mind when treating patients with subcutaneous emphysema. The
      misdiagnosis of this condition as its serious infective counterpart often leads
      to unnecessary aggressive treatment. Noninfective subcutaneous emphysema often
      accompanies a patient who has no systemic symptoms of illness. Unfortunately, the
      distinction is not always easy especially when history of injury suggests
      involvement of an infective or reactive element. Penetrating blackthorn injury is
      common, especially in rural communities, and often occurs from farming or
      gardening activities. Blackthorn penetration can cause numerous tissue reactions
      once embedded under the skin and they are often contaminated with soil. Here we
      present, for the first time, a case where penetrating blackthorn injury to the
      wrist resulted in noninfective subcutaneous emphysema involving the whole upper
      limb and neck, and its subsequent management.

PMID- 19177642
TI  - pH-amplified exponential growth multilayers: a facile method to develop
      hierarchical micro- and nanostructured surfaces.
AB  - We report a direct method to amplify the exponential growth of multilayers
      significantly by the alternating deposition of polyethylenimine (PEI) at high pH
      and poly(acrylic acid) (PAA) at low pH. The alternating pH switches the degree of
      ionization of the polyelectrolytes in the multilayers, which enhances the
      diffusion of PEI into and out of the film and hence increases the deposited mass
      per cycle. The synergetic action of the pH-tunable charge density and diffusivity
      of the weak polyelectrolytes provides a new method for the enhanced growth of
      multilayers with hierarchal micro- and nanostructured surfaces.

PMID- 19177643
TI  - Ripening of catanionic aggregates upon dialysis.
AB  - We have studied the dialysis of surfactant mixtures of two oppositely charged
      surfactants (catanionic mixture) by combining HPLC, neutron activation, confocal
      microscopy, and NMR. In mixtures of n-alkyl trimethylammonium halides and n-fatty
      acids, we have demonstrated the existence of a specific ratio between both
      surfactant contents (anionic/cationic almost equal to 2:1) that determines the
      morphology, the elimination of ions, and the elimination of the soluble cationic
      surfactant upon dialysis. In mixtures prepared with lower anionic surfactant
      contents, ill-defined aggregates are formed, and dialysis quickly eliminates the
      ion pairs (H+X-) formed upon surfactant association and also the cationic
      surfactant until a limiting 2:1 ratio is reached. By contrast, mixtures prepared
      above the anionic/cationic 2:1 ratio form micrometer-sized vesicles resistant to
      dialysis. These closed aggregates retain a significant number of ions (30%) over
      1000 hours, and dialysis is unable to eliminate the soluble surfactant. The
      interactions between surfactants have been estimated by measuring the
      partitioning of the CTA molecules between the catanionic bilayer, the bulk
      solution, and mixed micelles when they exist. The mean extraction free energy per
      CTA in the membrane has been found to increase by 1 kBT to 2 kBT as the soluble
      surfactant is depleted from the bilayer, which is enough to stop the dialysis.
      The vesicles produced above the anionic/cationic 2:1 ratio are formed by frozen
      bilayers and are resistant to extensive dialysis and therefore show an
      interesting potential for encapsulation as far as durability is concerned.

PMID- 19177644
TI  - Aggregation behavior of a new series of ABA triblock copolymers bearing short
      outer A blocks in B-selective solvent: from free chains to bridged micelles.
AB  - A combination of dynamic (DLS) and static (SLS) light scattering measurements was
      employed to study the self-assembly behavior of a new series of triblock
      copolymers bearing poly[5-(N,N-diethylamino isoprene)] (PAI) short outer blocks
      and polystyrene (PS) as the major middle block. Previously, it was verified that
      PAI outer blocks can be quaternized leading the formation of crew-cut aggregates
      in water (Riegel, I. C.; Eisenberg, A.; Petzhold, C. L.; Samios, D. Langmuir
      2002, 18, 3358). Herein, we focus on the copolymer's ability in the
      nonquaternized version to undergo self-aggregation in dimethylformamide (DMF), a
      selective solvent for the middle block. Light scattering measurements showed that
      formation of well-defined flowerlike micelles is likely to occur. Aggregates with
      a relatively narrow distribution, small average size, and number of aggregation
      ranging from 21 to 39 chains/micelle were experimentally observed. The results
      also suggested that approximately 5-6 polymeric units per each short outer block
      are needed to induce aggregation. The middle block length governs the size of the
      micelles and influences the number of aggregation of the resultant particles as
      well. Furthermore, when the polystyrene middle block was particularly long
      (degree of polymerization DP > 600), dynamic and static light scattering
      measurements suggested the formation of bridged micelles in an open structure in
      concentrations as low as 15 mg mL-1.

PMID- 19177645
TI  - Adsorption kinetics of amphiphilic diblock copolymers: from kinetically frozen
      colloids to macrosurfactants.
AB  - We investigated the spontaneous adsorption properties of charged amphiphilic
      diblock copolymers on hydrophobic surfaces and explained the transition of
      behavior from depleting frozen colloids (that do not adsorb at all) to fast
      adsorbing macrosurfactants when the hydrophobicity of the nonsoluble block is
      reduced. Three copolymer families have been used with the same hydrophilic block
      poly(acrylic acid), a weak acid whose ionization alpha can be varied by changing
      the pH. The hydrophobic blocks polystyrene, PS, poly(n-butyl acrylate), PBA, and
      poly(diethylene glycol ethyl ether acrylate), PDEGA, have interfacial tensions
      with water gammacore/solvent, respectively, of 32, 20, and 3 mN/m. We were mainly
      interested in the regime of high ionization alpha > 0.3, where PAA chains have no
      affinity for hydrophobic surfaces, and we verified experimentally that micelles
      do not adsorb directly. With the three copolymer families we show that the
      adsorption kinetics at an early stage is driven by the self-assembly properties
      in bulk solution: adsorption is hampered for PS-b-PAA (physically/kinetically
      frozen micelles in solution), controlled by unimer extraction for PBA-b-PAA
      (nonequilibrium micelles in solution with very low CMC < 10-4 wt %), and
      controlled by unimer diffusion and electrostatic repulsion for PDEGA-b-PAA
      (micelles at equilibrium in solution with high CMC is approximately 1-5 wt %).
      This explains the power law dependences of adsorption with concentration as C-1
      for PBA-b-PAA and C-2 for PDEGA-b-PAA. It is finally the interfacial tension with
      water of the nonsoluble block and not its glass transition that is the main
      control of bulk solution self-assembly and consequently of the adsorption
      kinetics properties of amphiphilic diblocks. We also proved by preparative GPC
      that the fraction of non-self-assembling diblock chains, which exists in all
      highly hydrophobic amphiphilic diblock systems, plays a negligible role in the
      adsorption properties. Finally, we investigated the intrinsic thermodynamic
      affinity between amphiphilic diblocks and hydrophobic surfaces. We show
      quantitatively that this affinity depends dominantly on the interfacial energies
      between the hydrophobic block, the surface, and water: diblocks with strongly
      hydrophobic nonsoluble blocks (PS, PBA) have a low affinity for weakly
      hydrophobic surfaces, and oppositely, diblocks with weakly hydrophobic nonsoluble
      block (PDEGA) have a universal affinity for hydrophobic surfaces (like small
      molecule surfactants but for different physical reasons). Finally, we showed via
      surface rheology that when adsorption occurs anchoring is strong and irreversible
      for very hydrophobic diblocks (PBA-b-PAA) and weaker and (partially) reversible
      for less hydrophobic diblocks (PDEGA-b-PAA).

PMID- 19177646
TI  - Cu-adatom-mediated bonding in close-packed benzoate/Cu(110)-systems.
AB  - Using UHV-STM investigations and density-functional theory calculations we prove
      the contribution of Cu-adatoms to the stabilization of a new high-density phase
      of benzoate molecules on a Cu(110) substrate. We show that two different chemical
      species, benzoate and benzoate Cu-adatoms molecules, build the new close-packed
      structure. Although both species bind strongly to the copper surface, we identify
      the benzoate Cu-adatoms molecules as the more mobile species on the surface due
      to their reduced dipole moment and their lower binding energy compared to
      benzoate molecules. Therefore, the self-assembly process is supposed to be
      mediated by benzoate Cu-adatom species, which is analogous to the gold-thiolate
      species on Au(111) surfaces.

PMID- 19177647
TI  - Adsorbed alpha-helical diblock copolypeptides: molecular organization, structural
      properties, and interactions.
AB  - In this work, we have developed 11-mercaptoundecanoic acid (MUA)-polypeptide
      "bilayer" systems by adsorbing poly(diethylene glycol-l-lysine)-poly(l-lysine)
      (PEGLL-PLL) diblock copolypeptide molecules of various architectures onto MUA
      functionalized gold substrates. An objective of our present work is to use the
      PEGLL-PLL/MUA bilayer as a model system for studying the interfacial phenomena
      that occur when PEGLL-PLL molecules interact with carboxylic acid (COOH) moieties
      of nanoparticle ligands. Specifically, we have elucidated the nature of the
      interactions between the PEGLL-PLL and COOH moieties as well as the resulting
      polypeptide conformation and organization, using a combination of surface
      techniques-grazing-incidence IR spectroscopy, ellipsometry, and contact angle. We
      have also thoroughly characterized other film properties such as the packing and
      graft density of the polypeptide molecules as a function of the PEGLL-PLL
      architecture. From the IR data, the adsorption process occurs primarily by means
      of electrostatic interaction between the protonated PLL residues (pKa
      approximately 10.6) and carboxylate moieties of the MUA self-assembled monolayer
      (SAM) (pKa approximately 6) that is enhanced by H-bonding. The PLL block is
      thought to adopt a random-coil (extended) conformation, while the PEGLL block
      that is not interacting with the MUA molecules is found to adopt an alpha-helical
      conformation with an average tilt angle of -60 degrees. The PEGLL-PLL molecules
      have also been deduced to form a heterogeneous film and adopt
      liquidlike/disordered packing on the surface. The average contact angle of the
      MUA-polypeptide bilayer systems is -40 degrees, which implies that the diethylene
      glycol (EG2) side chains of the PEGLL residues may be oriented somewhat toward
      the surface normal. From ellipsometry measurements, it is found that PEGLLx-PLLy
      molecules with a longer alpha-helical block are associated with a lower graft
      density on the MUA surface compared to those with a shorter alpha-helical block.
      This observation may be attributed to the greater repulsion-steric and H-bonding
      effects-that is imposed by the EG2 side chains found on and projected area
      occupied by the longer PEGLL block. The bilayer systems have been found to be
      extremely stable over a 2-week period with no changes in the contact angle,
      thickness, polypeptide tilt angle, or conformation. Beyond that, there is a
      gradual decrease in the thickness and increase in the contact angle of the
      bilayer that could be attributed to the oxidation of the MUA SAM molecules.

PMID- 19177648
TI  - Stainless steel grafting of hyperbranched polymer brushes with an antibacterial
      activity: synthesis, characterization, and properties.
AB  - Two strategies were used for the preparation of hyperbranched polymer brushes
      with a high density of functional groups: (a) the cathodic electrografting of
      stainless steel by poly[2-(2-chloropropionate)ethyl acrylate] [poly(cPEA)], which
      was used as a macroinitiator for the atom transfer radical polymerization of an
      inimer, 2-(2-bromopropionate)ethyl acrylate in the presence or absence of
      heptadecafluorodecyl acrylate, (b) the grafting of preformed hyperbranched
      poly(ethyleneimine) onto poly(N-succinimidyl acrylate) previously electrografted
      onto stainless steel. The hyperbranched polymer, which contained either bromides
      or amines, was quaternized because the accordingly formed quaternary ammonium or
      pyridinium groups are known for antibacterial properties. The structure, chemical
      composition, and morphology of the quaternized and nonquaternized hyperbranched
      polymer brushes were characterized by ATR-FTIR reflectance, Raman spectroscopy, X
      ray photoelectron spectroscopy, and atomic force microscopy. The peeling test
      confirmed that the grafted hyperbranched polymer films adhered much more strongly
      to stainless steel than the nongrafted solvent-cast films. The quaternized
      hyperbranched polymer brushes were more effective in preventing both protein
      adsorption and bacterial adhesion than quaternary ammonium containing poly(cPEA)
      primary films, more likely because of the higher hydrophilicity and density of
      cationic groups.

PMID- 19177649
TI  - Is there any microporosity in ordered mesoporous silicas?
AB  - The porous structure of nanostructured silicas MCM-41 and SBA-15 has been
      characterized using N2 adsorption at 77 K, before and after n-nonane
      preadsorption, together with immersion calorimetry into liquids of different
      molecular dimensions. Selective blocking of the microporosity with n-nonane
      proves experimentally that MCM-41 is exclusively mesoporous while SBA-15 exhibits
      both micro- and mesopores. Additionally, N2 adsorption experiments on the
      preadsorbed samples show that the microporosity on SBA-15 is located in intrawall
      positions, the micropore volume accounting for only approximately 7-8 % of the
      total pore volume. Calorimetric measurements into n-hexane (0.43 nm), 2
      methylpentane (0.49 nm), and 2,2-dimethylbutane (0.56 nm) estimate the size of
      these micropores to be < or = 0.56 nm.

PMID- 19177650
TI  - Gold nanoparticles at the liquid-liquid interface: X-ray study and Monte Carlo
      simulation.
AB  - The behavior of mixed-ligand-coated gold nanoparticles at a liquid-liquid
      interface during compression has been investigated. The system was characterized
      by measuring pressure-area isotherms and by simultaneously performing in situ X
      ray studies. Additionally, Monte Carlo (MC) simulations were carried out in order
      to interpret the experimental findings. With this dual approach it was possible
      to characterize and identify the different stages of compression and understand
      what happens microscopically: first, a compression purely in-plane, and, second,
      the formation of a second layer when the in-plane pressure pushes the particles
      out of the plane. The first stage is accompanied by the emergence of an in-plane
      correlation peak in the scattering signal and a strong increase of the pressure
      in the isotherm. The second stage is characterized by the weakening of the
      correlation peak and a slower increase in pressure.

PMID- 19177651
TI  - Fast disinfecting antimicrobial surfaces.
AB  - Silicon wafers and glass surfaces were functionalized with facially amphiphilic
      antimicrobial copolymers using the "grafting from" technique. Surface-initiated
      atom transfer radical polymerization (ATRP) was used to grow
      poly(butylmethacrylate)-co-poly(Boc-aminoethyl methacrylate) from the surfaces.
      Upon Boc-deprotection, these surfaces became highly antimicrobial and killed S.
      aureus and E. coli 100% in less than 5 min. The molecular weight and grafting
      density of the polymer were controlled by varying the polymerization time and
      initiator surface density. Antimicrobial studies showed that the killing
      efficiency of these surfaces was independent of polymer layer thickness or
      grafting density within the range of surfaces studied.

PMID- 19177652
TI  - Self-assembly of DNA arrays into multilayer stacks.
AB  - We describe the self-assembly of multilayer hexagonal DNA arrays through highly
      regular interlayer packing. Slow cooling of a mixture of three single-stranded
      DNA sequences with various Mg2+ concentrations leads to the self-assembly of
      diverse multilayer architectures. The self-assembled aggregates were deposited
      onto mica surfaces and examined with atomic force microscopy. The size of the two
      dimensional arrays and subsequent stacking to form multilayer structures are
      highly dependent on Mg2+ concentration. DNA bilayers and multilayers of defined
      shape are favored in 2-5 mM Mg2+ with an average lateral size of 700 nm. Arrays
      are much larger (up to 20 microm across) in 10-15 mM Mg2+, although multiple
      layers still make up 20-60% of the observed structures. Domains within single
      layer architectures were identified using Moire pattern analysis. Distinct
      structural phases within the multilayer assemblies include two layers translated
      by 17.5 nm and interlayer rotations of 20 degrees and 30 degrees. Three layer
      assemblies have cubic close packing and taller multilayer architectures of 2D DNA
      sheets were also identified.

PMID- 19177653
TI  - Controlled polyelectrolyte coating of glass-supported metal nanostructures.
AB  - We investigated the coating of glass-supported gold nanostructures with
      polyelectrolyte multilayers. To achieve selective coating of either the metal or
      the glass, thiol and silane monolayers with different functionalities were used.
      Self-assembled monolayers of an oligo-(ethylene glycol)-terminated silane on
      glass allow for complete passivation and fully selective deposition of the
      polyelectrolytes on the metallic structures. This glass passivation forces more
      material on the gold than without use of this silane. Gold passivation was
      achieved on Au(111) but was not successful on the metallic nanostructures, giving
      rise to polyelectrolytes irregularly deposited on the nanoparticles in the form
      of blobs.

PMID- 19177654
TI  - Amphiphilic diblock copolymers for molecular recognition: metal-nitrilotriacetic
      acid functionalized vesicles.
AB  - Here we describe the design, synthesis, and characterization of new, metal
      functionalized, amphiphilic diblock copolymers for molecular recognition.
      Polybutadiene-block-polyethylenoxide copolymers were synthesized by living
      anionic polymerization and end group functionalized with nitrilotriacetic acid
      and tris(nitrilotriacetic acid). After complexation with nickel and copper, these
      groups are known to selectively bind to oligohistidine residues of proteins. The
      polymers were characterized by 1H NMR spectroscopy, size exclusion
      chromatography, electron paramagnetic resonance, and UV-vis spectroscopy.
      Mixtures of these polymers with the respective nonfunctionalized block copolymers
      self-assemble in aqueous solution into vesicular structures with a controlled
      density of the metal complex end-groups on their surface. The accessibility of
      these binding sites was tested using maltose binding protein carrying a terminal
      decahistidine moiety and His-tagged enhanced green fluorescent protein as model
      systems. Fluorescence correlation spectroscopy clearly showed a significant and
      selective binding of these proteins to the vesicle surface.

PMID- 19177655
TI  - Toward organization of cyano-bridged coordination polymer nanoparticles within an
      ionic liquid crystal.
AB  - Size controlled cyano-bridged coordination polymer nanoparticles Mn1.5[Cr(CN)6]
      have been synthesized and organized at the nanolevel by using the room
      temperature ionic liquid crystal (ILC) C12-MIMBF4. The as-obtained material was
      studied by transmission electron microscopy (TEM), differential scanning
      calorimetry (DSC), optical microscopy, and X-ray diffraction. These analyses
      reveal the presence of a long-range organization of cyano-bridged nanoparticles
      at the nanoscale level within the ILC phase. The magnetic study of these
      nanoparticles reveals an appearance of a nanocluster-glass-like regime caused by
      magnetostatic interactions between neighboring nanoparticles. The properties of
      these organized nanoparticles have been compared with the properties of
      nanoparticles of the same composition and stoichiometry obtained and randomly
      dispersed into the isotropic IL C10-MIMBF4.

PMID- 19177657
TI  - Elastic medium confined in a column versus the Janssen experiment.
AB  - We compute the stresses in an elastic medium confined in a vertical column, when
      the material is at the Coulomb threshold everywhere at the walls. Simulations are
      performed in 2 dimensions using a spring lattice, and in 3 dimensions, using the
      Finite Element Method. The results are compared to the Janssen model and to
      experimental results for a granular material. The necessity to consider elastic
      anisotropy to render qualitatively the experimental findings is discussed.

PMID- 19177658
TI  - A general theory of non-equilibrium dynamics of lipid-protein fluid membranes.
AB  - We present a general and systematic theory of non-equilibrium dynamics of multi
      component fluid membranes, in general, and membranes containing transmembrane
      proteins, in particular. Developed based on a minimal number of principles of
      statistical physics and designed to be a meso/macroscopic-scale effective
      description, the theory is formulated in terms of a set of equations of
      hydrodynamics and linear constitutive relations. As a particular emphasis of the
      theory, the equations and the constitutive relations address both the
      thermodynamic and the hydrodynamic consequences of the unconventional material
      characteristics of lipid-protein membranes and contain proposals as well as
      predictions which have not yet been made in already existing work on membrane
      hydrodynamics and which may have experimental relevance. The framework structure
      of the theory makes possible its applications to a range of non-equilibrium
      phenomena in a range of membrane systems, as discussions in the paper of a few
      limit cases demonstrate.

PMID- 19177656
TI  - Direct observation of counterion organization in F-actin polyelectrolyte bundles.
AB  - Attractions between like-charged polyelectrolytes have been observed in a variety
      of systems (W.M. Gelbart, R.F. Bruinsma, P.A. Pincus, V.A. Parsegian, Phys. Today
      53, September issue, 38 (2000)). Recent biological examples include DNA,
      filamentous viruses, and F-actin. Theoretical investigations on idealized systems
      indicate that counterion correlations play a central role, but no experiments
      that specifically probe such correlations have been performed. Using synchrotron
      X-ray diffraction, we have directly observed the organization of multivalent ions
      on cytoskeletal filamentous actin (a well-defined biological polyelectrolyte) and
      found an unanticipated symmetry-breaking collective counterion mechanism for
      generating attractions. Surprisingly, the counterions do not form a lattice that
      simply follows actin's helical symmetry; rather, the counterions organize into
      "frozen" ripples parallel to the actin filaments and form structures reminiscent
      of charge density waves. Moreover, these 1D counterion charge density waves form
      a coupled mode with twist deformations of the oppositely charged actin filaments.
      This counterion organization is not sensitive to thermal fluctuations in
      temperature range accessible to protein-based polyelectrolyte systems. Moreover,
      the counterion density waves are "pinned" to the spatial periodicity of charges
      on the actin filament even if the global filament charge density is varied,
      indicating the importance of charge periodicity on the polyelectrolyte substrate.

PMID- 19177659
TI  - [Application of traditional methods of rehabilitative medicine to the
      rehabilitation of neurooncological patients].

PMID- 19177660
TI  - [The role of physical exercises in the improvement of cognitive functions in
      patients who survived stroke, in the early rehabilitative period].
AB  - The objective of this work was to evaluate the efficacy of a complex of physical
      therapy exercises "Brain gymnastics" in post-stroke patients. Eighty three such
      patients enrolled in the study were randomly allocated to two groups. The program
      of physical rehabilitation for patients comprising one group (n = 41) included
      regular exercises with elements of "brain gymnastics" whereas patients of the
      other group (n = 41) received standard rehabilitative treatment. Patients of
      group 1 enjoyed improvement of cognitive functions, mood, and quality of life.
      Disturbances of short-term memory and voluntary attention were partly corrected,
      astheno-neurotic reactions and manifestations of advantage by illness became less
      apparent than in the control group while the level of self-assessment increased.
      None of the patients in group 1 exhibited undesirable reactions to the offered
      treatment.

PMID- 19177661
TI  - [Comparative efficacy of non-medicamentous methods for the treatment of patients
      with neurotic anxiety disorders].
AB  - The objective of this work was to compare effectiveness of non-medicamentous
      methods for the treatment of patients with neurotic anxiety disorders. The study
      included 193 patients at the age from 18 to 40 years. They were offered the
      following methods of non-medicamentous therapy: psychotherapy, phytotherapy, and
      reflexotherapy (acupuncture). Psychotherapy was the first-line treatment while
      phytotherapy and reflexotherapy were used as adjuvant modalities. Patients of the
      control group received psychotherapy alone. The study has demonstrated relatively
      high efficiency of non-medicamentous therapies in the patients with neurotic
      anxiety disorders. It was shown that psychotherapy not only provides a solid
      basis for application of the second treatment modality but can also be used as a
      self-contained method. The best results were obtained by combined treatment based
      on cognitive and behavioural psychotherapy, hypnosis, and autogenic training as
      its major components. Their most important outcomes were modification of basic
      skills, habit patterns, and mode of thinking as well as self-care education of
      the patients.

PMID- 19177662
TI  - [Colour rhythmotherapy for the correction of psychosomatic visual abnormalities
      in patients with chronic ophthalmopathia].

PMID- 19177663
TI  - [Effect of longidase ultraphonophoresis on skin microbiocenosis in patients with
      acne].
AB  - Results of clinical examination and laboratory analysis as well as treatment of
      patients with torpid inflammatory forms of acne resistant to long-term
      antimicrobial therapy are presented and discussed. The combined treatment
      included longidase ultraphonophoresis that produced beneficial effect on the
      patients' dermatological status. Results of the study suggest the possibility of
      efficacious correction of the disturbed skin microbiocenosis. Specifically,
      concentration of all microorganisms sampled and cultured in the follow-up period
      did not exceed 10 4 CFU/ml. The amount of pathogenic flora (Staphylococcus
      haemoliticus and S. aureus) on the skin surface in 23% of the patients was
      significantly smaller than before the initiation of therapy. In 66.7% of the
      patients, the skin was totally free from Staphylococci of both species.

PMID- 19177664
TI  - [Effectiveness of photo- and mesophotophoresis in the combined treatment of
      patients with chronic generalized parodontitis].

PMID- 19177665
TI  - [A variant of the computerized program algorithm of a physiotherapist automated
      workplace based on the sequence of operations in a department].

PMID- 19177666
TI  - [The use of radon baths in the combined sanatorium-and-spa treatment of patients
      with irritated bowel syndrome: medical technology].

PMID- 19177667
TI  - Reform a la carte. CBO weighs the costs, savings of more than 100 reform
      proposals, giving lawmakers a foundation tto work from.
AB  - Lawmakers have a wealth of options for reform laid out in two new CBO reports.
      "This was vintage CBO, a thorough, thoughtful compendium that illustrates the
      complexities and challenges facing policymakers," said Steven Spell, of the FAH,
      left.

PMID- 19177668
TI  - HIMSS sees opportunity. Group looks to Obama to fund health IT.

PMID- 19177669
TI  - Public display. New Web site aims to track health progress.

PMID- 19177670
TI  - More reports to come. IOM, HHS tapped to tackle clinical effectiveness.

PMID- 19177672
TI  - Where's the plan? Adverse-event reports say what's already known.

PMID- 19177671
TI  - Action on antibiotics lacking. Most hospitals still aren't managing use: survey.

PMID- 19177673
TI  - Scanning for alternatives. Studies: CT scans might be way to find blockages.

PMID- 19177674
TI  - Critics assail HHS initiative. Framework described as lacking privacy
      protections.

PMID- 19177675
TI  - Hedge trimmer. Madoff fallout spotlights hedge-fund risks.

PMID- 19177676
TI  - A deficit of trust. After what we've seen in 2008, maybe the new year will bring
      welcome changes.

PMID- 19177677
TI  - Bump in the rug. Healthcare reform could be costly in a different way for
      military.

PMID- 19177678
TI  - Pinnaplasty--a dwindling art in today's modern NHS.

PMID- 19177679
TI  - FAQs, facts, myths and misconceptions about medical malpractice 2.

PMID- 19177680
TI  - Stents and medication therapy offer equal Angina relief after three years. 
      Stents may provide quicker relief and may be best suited for more serious cases,
      but drug therapy alone is sometimes enough to achieve similar results.

PMID- 19177681
TI  - Blood pressure--measuring device eliminates "white coat effect."  The new BpTRU
      system takes several readings without a nurse present in order to arrive at your
      most accurate blood pressure reading.

PMID- 19177682
TI  - Vitamin D may help keep your heart strong.  However, more studies are needed
      before a clear link can be established.

PMID- 19177683
TI  - Protect your heart from cold weather inflammation.  Falling temperatures put
      heart patients at risk.

PMID- 19177684
TI  - Lipid control may require more than a statin.  Additional medications or
      lifestyle changes may be necessary to lower total bad cholesterol and raise good
      cholesterol.

PMID- 19177685
TI  - Which medication is usually recommended to treat atrial fibrillation after
      ablation?

PMID- 19177686
TI  - By the way, doctor. What should an exam for skin cancer include?

PMID- 19177687
TI  - Electron spin resonance characterization of the radicals produced by enzymatic or
      chemical cleavage of vicine.
AB  - Vicine is a glucoside from broad beans (Vicia faba) that is hydrolyzed upon
      ingestion to the unstable aglycon divicine, the autoxidation of which has been
      implicated in the onset of hemolysis in favism,possibly via production of
      superoxide and hydrogen peroxide. The autoxidation of divicine proceeds through a
      series of reactions involving the formation of a radical species. In this study
      divicine radicals were produced either by incubation of vicine with beta
      glucosidase or by boiling vicine in hydrochloric acid. On the basis of electron
      spin resonance spectra, it was shown that the two treatments produce different
      radicals. By spectral simulation the acid-produced radical was demonstrated to be
      a deaminodivicine. The autoxidation rates of the two radicals were determined
      from the disappearence of their electron spin resonance signals in the presence
      of air: at physiological pH the enzymatically produced divicine radical was much
      more stable to oxygen than the chemically produced radical. The two radicals may
      thus be expected to behave differently in a biological system. The repercussions
      of these findings could be considerable, given that most of the pharmacological
      and biochemical studies on vicine action have been done with the chemically
      produced compound, which is shown here to be an unphysiological intermediate.

PMID- 19177688
TI  - [Soldiers or immigrants: the army as an avenue of migration to Rio de la Plata
      for poor Spaniards in late colonial times].

PMID- 19177689
TI  - Ethnicity, region and nation: Valencian identity and the Spanish nation-state.

PMID- 19177690
TI  - Racialization: the genealogy and critique of a concept.

PMID- 19177691
TI  - Ethnicity, assimilation and nation in plural Suriname.

PMID- 19177693
TI  - Safety assessment of cosmetics in Europe. Foreword.

PMID- 19177694
TI  - The East European Gypsies in the Imperial Age.

PMID- 19177695
TI  - Safety assessment of cosmetics in Europe. Preface.

PMID- 19177696
TI  - Peasant mining production as a development strategy: the case of women in gold
      mining in the Brazilian Amazon.

PMID- 19177697
TI  - Black Orpheus and the merging of two Brazilian nations.

PMID- 19177698
TI  - Czech attitudes towards the Roma: "expecting more of Havel's country"?

PMID- 19177699
TI  - Environmental policy reform in the post-Communist Czech Republic: the case of air
      pollution.

PMID- 19177700
TI  - Life quality assessment among patients with vitiligo: comparison of married and
      single patients in Iran.
AB  - BACKGROUND AND AIMS: Vitiligo is known to affect the quality of social and
      personal life in some countries. This study aims to assess the quality of life
      (QOL) in vitiligo sufferers among the Iranian population and to evaluate its
      relation with different variables. METHODS: One hundred vitiligo patients
      answered a questionnaire based on the Dermatology Life Quality Index (DLQI).
      RESULTS: The mean DLQI score was 8.16. There were statistically significant
      relationships between DLQI scores and marital status, skin phototype, and disease
      extension independently. CONCLUSIONS: This study shows that vitiligo has a major
      impact on the QOL of patients in Iran. Hence dermatologists should pay attention
      to the psychological effects of this cosmetic disease and try to decrease its
      extension and disfiguring effects by various treatments.

PMID- 19177701
TI  - Clinical and sociodemographic  study of vitiligo.

PMID- 19177702
TI  - A study of clinicohistopathological correlation in  patients of psoriasis and
      psoriasiform dermatitis.
AB  - BACKGROUND: Psoriasis has different clinical variants, which mimic diverse
      dermatological conditions and may require a histopathological confirmation of the
      diagnosis. Studies to establish a clinicohistopathological concordance (and its
      determinants), in psoriasis and psoriasiform dermatitis are lacking. AIMS: The
      present study was designed (a) to correlate the clinicohistopathological features
      of psoriasis and psoriasiform dermatitis, and (b) to identify determinant(s) that
      may contribute to the diagnosis of psoriasis and psoriasiform dermatitis.
      METHODS: This was a prospective study involving 100 patients, with a single
      clinical diagnosis of psoriasis or with psoriasis as one of the differential
      diagnoses, and its correlation with histopathological features. RESULTS: The
      clinical features of typical scale (P = 0.0001) and Auspitz's sign (P = 0.0001),
      and histological evidence of suprapapillary thinning (P = 0.0001) and absent
      granular cell layer (P = 0.0001) were found to be statistically significant
      contributors to the clinicohistological concordance in cases of psoriasis.
      Vertical orientation of collagen bundles (P = 0.0001) and lymphocytic exocytosis
      (P = 0.003) were found to be significantly associated with diagnosis of
      psoriasiform dermatitis. CONCLUSION: The present study reconfirms the diagnostic
      accuracy of silvery white scale, Auspitz's sign, and Koebner's phenomenon in a
      clinical setting suggestive of psoriasis. However, in their absence, histological
      evidence of suprapapillary thinning and absent granular layer, in addition to the
      Munro microabscess and Kogoj's abscess, may contribute to the diagnosis of
      psoriasis. Similarly, vertical orientation of collagen bundles and lymphocytic
      exocytosis may point toward a diagnosis of psoriasiform dermatitis.

PMID- 19177703
TI  - Polymerase chain reaction is no better than Gram stain for diagnosis of
      gonococcal urethritis.

PMID- 19177704
TI  - Italian women after development: employment, entrepreneurship, and domestic work
      in the Third Italy.

PMID- 19177705
TI  - "We are family": gender, microenterprise, family work, and well-being in Ecuador
      and the Dominican Republic -- with comparative data from Guatemala, Swaziland,
      and Guinea-Bissau.

PMID- 19177706
TI  - To punish, treat, or pardon: French society and the enuretic child in the
      nineteenth and twentieth centuries.

PMID- 19177708
TI  - Closing thoughts ... Boomers.

PMID- 19177707
TI  - Father-child relations in France: changes in paternal authority in the nineteenth
      and twentieth centuries.

PMID- 19177709
TI  - Paths toward autonomy: the living conditions of fostered children in western
      France in the early 20th century.

PMID- 19177711
TI  - Health concepts in different contexts.

PMID- 19177710
TI  - Higher offspring mortality risks with maternal and paternal schizophrenia and
      other severe mental disorders: elevated risks persist beyond the neonatal period.

PMID- 19177712
TI  - Social representations of health and illness among 'baby-boomers' in eastern
      Canada.
AB  - For several decades, government agencies in the western world have promoted
      personal responsibility for health and illness. This study explored the extent to
      which this perspective was integrated into the everyday beliefs about health and
      illness held by a sample of baby-boomers from eastern Canada. Approximately 150
      baby-boomers participated in a series of individual interviews and group
      discussions. Detailed analysis of their conversation revealed a number of social
      and personal narratives about the changing character and experience of health and
      illness. The dominant viewpoint was in terms of lifestyle and personal
      responsibility. We consider the role of narratives in the construction of social
      representations of health and illness.

PMID- 19177713
TI  - 'Would you consider yourself a healthy person?': using focus groups to explore
      health as a moral phenomenon.
AB  - Recent psychological, sociological and cultural theory has suggested that health
      has become a moral phenomenon. The main aim of this paper is to illustrate how
      focus groups constitute a particularly useful method of investigating the way in
      which people routinely engage in moral reasoning in the course of conversations
      and debates regarding health related issues. The four focus groups drawn upon in
      this study formed part of a larger study whose aim was to explore attitudes
      towards health and a theoretically postulated increasing 'resistance' to health
      promotion amongst the general public. Accordingly, the focus groups covered
      themes such as: concepts of healthy and unhealthy; individual responsibility for
      health; attitudes and responses to health promotion; public trust in medicine,
      science, doctors and health information; and the relationship between health,
      individual freedom and government intervention.

PMID- 19177714
TI  - Intrinsic motivation towards sports in Singaporean students: the role of sport
      ability beliefs.
AB  - This study investigated determinants of active lifestyles in Singaporean
      university students. Using confirmatory factor analysis, a measure of lay beliefs
      concerning athletic ability was confirmed. Other results confirmed hypotheses
      that beliefs reflecting that athletic ability can be developed over time
      (incremental beliefs) predict an achievement task (self-referenced) orientation,
      while beliefs reflecting that athletic ability is relatively stable (entity
      beliefs) predict an ego (other-person, comparative) orientation. Goal
      orientations directly affect perceived competence which, in turn, influence
      intrinsic motivation to be physically active. A task orientation had a direct
      link to intrinsic motivation. Results suggest that intrinsic motivation towards
      sport and physical activity might be enhanced through interventions that focus on
      self-referenced and self-improvement notions of ability as well as perceived
      competence.

PMID- 19177715
TI  - Thresholds of morbidity among women in a peri-urban community of Maharashtra,
      India: conceptual and methodological issues.
AB  - While data on perceived morbidity often correlate poorly with clinical morbidity,
      they can provide an indicator for how women's concepts of health change in the
      context of larger transitions in gender and health systems. Drawing on multiple
      sources of data on perceived morbidity among women in a peri-urban settlement of
      Maharashtra, India, this article examines variations in women's thresholds for
      articulating illness conditions. Data on women's health were collected from
      married women aged 15-49, using four different instruments: focus group
      discussion guides; general illness narrative guidelines; individual open-ended
      questions about morbidity; and a highly structured checklist. Comparing the data
      and the assumptions underlying these instruments, the article identifies four
      different thresholds relating to situational, agency, prototypical and
      dimensional aspects of women's experience and subsequent reporting of morbidity.

PMID- 19177716
TI  - Health in the context of growing old: social representations of health.
AB  - Senior citizens have become a major part of the clientele of general
      practitioners and home care nurses due to a major demographic transition in most
      western countries. How do the health concepts in professional practice reflect
      these trends? Research has largely investigated the health concepts of lay
      people. This study is focused on the representations of health in old age held by
      two groups of professionals--general practitioners and nurses--both working in
      home care with elderly people in two German cities. The results show how health
      professionals use an extended concept of health, which focuses on the life
      situation of the old person, on autonomy, self-determination or independence and
      on how the elderly manage disease and physical restrictions.

PMID- 19177717
TI  - Living with diabetes in rural and urban Ghana: a critical social psychological
      examination of illness action and scope for intervention.
AB  - Current chronic illness research in Africa neglects the social psychological
      dimensions of illness experiences that present more appropriate frameworks for
      intervention. Informed by social representations theory, links between social
      knowledge of diabetes, illness experience and illness action were examined
      through semistructured individual interviews with rural and urban Ghanaians with
      diabetes. All respondents drew interchangeably from commonsense, scientized, and
      religious knowledge modalities in defining health, illness and diabetes. Diabetes
      caused disruption to: body-self, social identity, family/social relationships,
      economic circumstance and nutrition. Commonsense and scientized notions of
      health, illness and diabetes framed illness action goals that merged with
      biomedical goals, specifically drug and diet management. These goals were
      compromised by the nature, severity and duration of disruption(s) and emotional
      responses evoked. The paper dicusses implications of the findings and outlines
      recommendations for interventions that span individual/group, community and
      structural dimensions.

PMID- 19177718
TI  - Conception of wellness in families with a diabetic child.
AB  - Focusing on wellness and adopting perspectives from positive and perceptual
      psychology, perceptions about health and illness were studied in 55 families with
      diabetic children, their siblings (8-17 years old) and mothers. Individual
      interviews were conducted on definitions of wellness, rationale for children's
      self-evaluation of wellness, consequences of wellness and definition of diabetes.
      Content analysis revealed that respondents have a comprehensive definition of
      wellness focusing on adaptation and performance. Significant role-specific
      differences emerged. Mothers' perceptions reflected their role in caregiving and
      socializing children. Children emphasized school performance and absence of
      health problems. Siblings focused on harmonious relationships. In accordance with
      the perspective of positive psychology, adults' as well as children's perceptions
      are congruent with the pursuit of wellness despite chronic illness.

PMID- 19177719
TI  - Illness representations in families with a chronically ill adolescent:
      differences between family members and impact on patients' outcome variables.
AB  - The impact of parents' illness representations on well-being and illness-related
      strain of adolescents suffering from a chronic skin disease was examined. Because
      family characteristics have proved to be important for coping, adolescents'
      perceived family cohesion was also assessed. Five categories of illness
      representations (causes, control, timeline, curability, and effective treatments)
      were assessed from 30 adolescents and their parents. Comparisons revealed
      differences between family members' illness representations. Perceived family
      cohesion was a good predictor of adolescents' wellbeing and strain, whereas
      parents' illness representations had only little impact. In families with high
      similarity between the parents' illness representations, the adolescents reported
      more well-being. Results are discussed with regard to developmental
      characteristics of adolescence, nature of outcome variables and methodological
      problems.

PMID- 19177720
TI  - The transformation of social representations of chronic disease in a self-help
      group.
AB  - A Participant Action Research process was carried out with individuals affected
      by Inflammatory Bowel Disease, more specifically Crohn's Disease and Ulcerative
      Colitis. The results show evidence of a transformation of social representations
      of disease. 'Normalization' is the central component of the transformation,
      indicating the achievement of a more restricted representation of the illness.
      This change is an attitudinal modification, which is characterized by higher
      tolerance of the disease--accepting its chronic nature and the limitations it
      imposes on daily life--, acceptance of the possibility of being supported by
      others in facing the disease, and the recognition of a transformational process
      that involves different stages in dealing with and accepting the disease.

PMID- 19177721
TI  - Social representation of AIDS among Zambian adolescents.
AB  - This study explores shared thinking about HIV/AIDS among Zambian adolescents.
      With high numbers affected, the question is how this group represents its risk.
      Social representations of the origin, spread and risk of HIV/AIDS were gleaned
      via 60 semistructured interviews with urban 15 to 20 year olds. A systematic
      analysis revealed a shared picture: AIDS was linked to the West, God and teenage
      girls; its spread lay beyond the control of adolescent boys and men; and the
      personal sense of vulnerability was low. The results are discussed in light of
      their corroboration of the finding that social representations of danger can be
      identity protective, yet also system justifying. The potential transfer of such
      findings to psychological theory and to health campaigns is considered.

PMID- 19177722
TI  - Beyond otherness: controllability and location in mental health service clients'
      representations of mental health problems.
AB  - This paper focuses on a multi-method qualitative study of the social
      representations of mental health problems held by clients of the mental health
      services. Clients appear to represent mental health within representational
      projects, and, in the course of these projects, situate mental health problems at
      various points within a two-dimensional representational structure comprising
      controllability and location. It will be suggested that the element of Otherness,
      so integral to public representations of mental ill health, is therefore
      significantly more complicated in clients' representations. Similarly, the
      interaction between these two dimensions suggests that clients move beyond the
      professional divide between psychosis and neurosis. The implications of these
      results will be briefly considered.

PMID- 19177723
TI  - Concepts and understandings of dementia by 'gatekeepers' and minority ethnic
      'service users'.
AB  - In this article I outline research which seeks to explore the intersections of
      dementia, ethnicity and family care. My focus is how research that aims to focus
      on dementia care and ethnicity illuminates the experiences of members of
      minoritized ethnic groups in accessing statutory services. I reflect on how the
      intersections of racialized identities and western medical terminology make
      researching and providing services across racialized boundaries and
      health/illness a complex procedure. This commentary has direct implications for
      the care of people with dementia, their family members and for service
      development within health and social care fields.

PMID- 19177724
TI  - Have we made progress? The Clinical Placement Pilot Project update.

PMID- 19177725
TI  - Effect of non linearity of PDL on a restored tooth.
AB  - To obtain an accurate stress distribution pattern of the restored tooth, taking
      into account non linear properties of Periodontal Ligament (PDL), linear stress
      and deformation analysis was carried out with four posts, different in
      constitution and shape. However, as the PDL exhibits non linear behaviour, more
      accurate results could be expected by simulating the model for non linear
      properties of PDL. Due to computational difficulties, a simplified model was
      prepared and non linear stress analysis was carried out. In case of non linear
      analysis the stresses were decreased by 25% and deformation was increased by 50%
      approximately as compared to linear static analysis of the restored maxillary
      central incisor.

PMID- 19177726
TI  - Methods used in dentine bonding tests: an analysis of 102 investigations on bond
      strength.
AB  - Bond strength testing of resin-based materials to dentine may provide evidence as
      to the potential effectiveness of a dentine-bonding agent in producing adhesion
      and minimising microleakage. The purpose of this analysis was to analyse the
      methods used in 102 recently-published investigations on bond strength tests of
      resin composite to dentine. One hundred and two papers, published during the
      years 1998 to 2002 on the subject of bond strength measurement of resin composite
      to dentine were identified from a literature search. These papers were assessed
      for their inclusion of the following variables: type of test, thermal cycling
      regime, tooth notation, storage medium, preparation of dentine surface, rate of
      load application, type of dentine, film thickness, dimensions of surface area
      contact and time of testing. Shear testing was the most common type of test, used
      in 46% (n=47) of the papers analysed, human dentine was used in 77% (n=79) of the
      investigations, and 24 h post-placement was the predominant time of specimen
      testing (67%, n=68). Surface area of contact, or specimen diameter, was stated in
      65% (n=66) of the papers analysed. A number of variables were not stated in a
      majority of papers. There was little standardization of test methods and a number
      of potentially significant variables may not be reported or recorded in bond
      strength determinations which limit the overall standardization between different
      test centres.

PMID- 19177727
TI  - Bonding of crown and bridge adhesive resins to dentine.
AB  - The shear bond strength of three adhesives, Panavia 21, Superbond, All Bond C&B
      Cement, and Variolink (a dual cure resin) to various dentine depths were
      determined. Fifteen human fully erupted permanent first and second molars were
      wet ground using 500 and then 800 grit abrasive papers to expose the superficial,
      middle and the deep dentine, for each adhesive tested. Five samples were prepared
      for each dentine depth. The adhesives were bonded to the samples using gelatine
      capsules and were matured for 24 h in water at 37 degrees C. The samples were
      debonded in shear using tensile testing machine at a cross-head speed of 1
      mm/min. The data were analysed using ANOVA and the Tukey test. The fracture
      surfaces were examined by optical microscopy. The bond strength of Superbond to
      dentine was significantly higher (P<0.05) than any of the materials tested. The
      bond strength of all materials tested was shown to be affected by dentine depth,
      except for Superbond. Fractured dentine specimens showed that the samples of
      Superbond are almost cohesive (>90%), and the samples of other adhesives are
      mostly adhesive (>70%). These results confirm that Superbond is capable of
      forming a bond at various dentine depths.

PMID- 19177728
TI  - Bonding of adhesive resin luting agents to metal and amalgam.
AB  - The shear bond strength of three adhesives, Panavia 21, Superbond, All Bond C&B
      Cement, and a dual cure resin (Variolink), to Ni-Cr-Be (Rexillium III), Midigold
      (Type III gold) and Amalgam (Sybraloy) were determined. Fifteen samples were
      prepared using 800 grit abrasive papers for Ni-Cr and Midi-Gold, and 100 grit
      papers for amalgam. Ni-Cr-Be and Midi-Gold samples were sandblasted for 30 s and
      steam cleaned for 10 s. The adhesives were bonded to the samples using gelatine
      capsules and were matured for 24 h in water at 37 degrees C. The samples were
      debonded in shear using an Instron at a cross-head speed of 1 mm/min. The data
      was analysed using ANOVA and a Tukey test. The bond strength of Superbond to both
      metal alloys was significantly higher (P<0.05) than any of the materials tested,
      with the exception Panavia 21 to gold. The bond strength of All Bond C&B cement
      had shown to be not significant difference from those of Panavia 21 and
      Variolink, when bonded to Rexillium and Midi-Gold, respectively. The bond
      strength of All Bond C&B Cement to amalgam was significantly greater (P<0.05)
      than those of the other materials tested. The shear bond strength to gold showed
      lower bonding for all adhesives when compared with Rexillium (P<.001). The
      ranking of bond strength to both alloys was as follows: Superbond>Panavia 21>All
      Bond C&B>Variolink. The nature of substrate to be used for bonding and the
      adhesive material itself are important factors in bonding which can be achieved
      between cast metals and prepared teeth with amalgam filling. Superbond should be
      successful as an adhesive for the attachment of all substrates tested, with the
      possible exception of amalgam, for which All Bond C&B Cement gives the best
      result.

PMID- 19177729
TI  - Mould filling of Ag-Pd-Cu-Au and Ag-Zn-Sn-In alloy castings made using a rapidly
      prepared gypsum-bonded investment material.
AB  - Mandibular premolar-shaped wax patterns of full crowns with a marginal angle of
      300 were prepared. Two semiprecious alloys were cast using a rapidly prepared
      gypsum-bonded investment material or a conventional gypsum-bonded investment. A
      precise impression was taken and cut into four segments. Scanning electron
      microscopy was used to evaluate the mould filling of each segment. The mould
      filling of the silver-palladium-copper-gold alloy was worse than that of the
      silver-zinc-tin-indium alloy. The mould filling of both alloys cast with the
      rapidly prepared gypsum-bonded investment material was superior to that using the
      conventional investment.

PMID- 19177730
TI  - A pilot survey of dental health in a group of drug and alcohol abusers.
AB  - This study was designed to provide a broad estimate of the level of dental
      disease in a group of patients attending a Regional Addiction Unit, and outline
      some of the perceptions of this group with regard to the importance of dental
      health and gaining access to dental services. In a survey of consecutive patients
      admitted to a day Hospital Service at a Regional Addictions Psychiatry Unit, 50
      patients were with either opiate or alcohol dependence were surveyed and asked a
      range of questions in relation to their dental health. A basic dental examination
      was carried out. The majority of patients had either moderate or severe dental
      disease. Disease levels were higher among opiate abusers compared to alcohol
      abusers. A large majority of patients had experienced dental problems within the
      preceding year and there was found to be a problem in accessing dental care for
      this group of patients. Improving dental care for this group of patients presents
      various challenges given the high rates of dental disease and poor access to
      dental services.

PMID- 19177731
TI  - Research approaches in prosthodontics.
AB  - Many current studies of prosthodontic treatment use patient-based outcomes.
      Traditionally, these outcomes are measured using quantitative methods. However,
      qualitative research methods can provide important information that cannot be
      found using quantitative techniques. In this article, the authors review
      quantitative and qualitative research studies. Differences, advantages and
      disadvantages of each method are highlighted. Prosthodontic researchers are
      encouraged to combine these methods to benefit from the potential of each of
      these approaches.

PMID- 19177732
TI  - [Rare diagnosis of CD4+56+ leukemia from dendritic cells type DC2].
AB  - CD4+56+ hematodermic neoplasm or leukemia from early plasmocytoid dendritic cells
      type DC2 was recognized by WHO-EORTC classification of cutaneous lymphomas as a
      separate entity related to the plasmacytoid precursor dendritic cell (pDC). This
      diagnosis is based on expression of CD4 and CD56 antigens and absence of B, T or
      myeloid lineage markers. Immunohistochemistry and flow cytometry are the only
      methods, which allow identification of this disease, either in isolated skin
      lesions or in a leukemic form. Although the co-expression of CD4 and CD56 is rare
      and the number of described cases is low, this group bears similar
      characteristics in a clinical course of disease. It is a very aggressive
      leukemia/lymphoma, usually with primary skin involvement, in half of the cases
      infiltrating bone marrow or lymph nodes. Despite high rate of initial response to
      treatment, early and widespread relapses occur and patients die of disease
      progression. Although the physiological counterpart of tumour cells was
      identified, the origin of the disease is still discussed because of aberrant
      expression of cell markers. Optimal treatment is not known. However, this
      aggressive disease requires radical approach with intensive chemotherapy
      regimens, prophylaxis of CNS involvement and early indication of allogeneic bone
      marrow transplantation. Two case reports are described.

PMID- 19177733
TI  - [Feedings of critical care patients by endoscopic three-luminal tube--a
      retrospective analysis].
AB  - BACKGROUND: Enteral nutrition (EN) represents a preferred type of nutritional
      support in critical care patients, in spite of the high incidence of intolerance.
      One of the methods which can speed up the delivery of adequate amounts of food is
      to switch from the gastric to post-pyloric feeding. A three-luminal tube (TLT)
      enables post-pyloric enteral feeding with accompanying gastric decompression. The
      aim of our study was to evaluate effectiveness and safety of the endoscopically
      introduced TLT along with the estimation of the adequate dose of enteral
      nutrition. METHODS AND RESULTS: Retrospective analysis of 111 critical care
      patients with 140 introduced TLT during 2003 to 2006 in two intensive care units
      (UIC) in the Teaching hospital in Plzen included patients of average age 54 years
      (+/- 15), APACHE II score 26 (+/- 10) and UIC mortality was 24%. Eight
      introductions were technically not successful (6%). Reintroduction of the tube
      was necessary in 21 patients (19%). The average time of tube introduction was 6
      minutes (+/- 3). In direct relation to endoscopy no serious complication was
      observed. In our cohort, 34 ventilator-associated pneumonias developed (31%).
      Average time interval since the admission to the hospital till TLT introduction
      was 7 days (+/- 6). Evaluation of a subgroup of 77 patients from one UIC has
      shown that the adequate amount of EN was achieved in 82% of patients in 4 days
      (+/- 3) after the TLT introduction. In average, TLT was introduced for 11 days
      (+/- 7). CONCLUSIONS: Endoscopic TLT introduction represents a safe and reliable
      method which can ensure adequate amount of enteral nutrition in majority of
      critical care patients with gastrointestinal dysfunction. In our conditions, TLT
      is probably not sufficiently used.

PMID- 19177734
TI  - [Duodenal atresia and stenosis].
AB  - BACKGROUND: Analysis of results of surgical treatment of congenital duodenal
      obstruction at authors' institution. METHODS AND RESULTS: Retrospective analysis
      of demographic and clinical data collected from hospital and outpatient
      documentation. Age at operation, sex, type of duodenal obstruction, associated
      anomalies, type of operation, time of parenteral nutrition, onset of enteral
      nutrition, early and late complications were recorded and analyzed. Between
      January 1991 and December 2006, 77 patients (female to male ration 1.6:1) with
      duodenal obstruction were operated on. Among them there were 48 patients with
      duodenal atresia, 20 with duodenal membrane and 9 with annular pancreas. The
      average age at operation for duodenal atresia was 2.15 days, most patients (33
      i.e. 43%) were operated on the 1st day of life. The average age at operation for
      duodenal membrane and annular pancreas was 7, 35 and 5, 8 days. In 33 patients
      diamond duodenoduodenoanastomosis (Kimuraes procedure) was performed, excision of
      membrane was the second most frequent operation (22 times). We noted
      complications in 38 patients, the most common one was sepsis (14 cases) followed
      by gastroesophageal reflux (6 times). The mortality in our group was 9,1%--7
      infants. One death only was caused by a surgical complication--anastomotic
      leakage. The period of follow-up was 5 months to 16 years. CONCLUSIONS:
      Congenital duodenal obstruction has, with appropriate surgical treatment, a good
      long and short-term prognosis. Ninety to 95% of patients survive without
      significant sequellae. The mortality is low and is caused by associated
      malformations, the principal cause of death is sepsis.

PMID- 19177735
TI  - [Suicidal attempts within the set of young adult parents of children observed in
      ELSPAC study].
AB  - BACKGROUND: Though effective medications for the treatment of mood disorders have
      been developed, panic anxiety, major depression and other psychiatric diseases,
      only small reduction in suicide rates has been achieved during last four decades.
      Further epidemiological, clinical and experimental studies are initiated to
      support both prevention and treatment of suicidal behaviour. METHODS AND RESULTS:
      In ELSPAC study, the data of 3148 men and 3637 women--parents of children aged 3
      years--were analysed with the aim to detect possible determinants of psychiatric
      disorders. These data included both information about the parents' events and
      health after the child's delivery and about parents' history during their own
      childhood. According to their self-reported suicidal attempts during last 18
      months, parents were divided into groups A (with positive history) and B (no
      attempt). Statistical significance was evaluated by the SPSS programme (Pearson's
      chi-square test, linear-by-linear associations, ANOVA). 23 persons (0,3%) overall
      self-reported the suicidal attempt during last 18 months: 18 men (0,6%) and 5
      women (0,1%). Among them, 2 men and 4 women repeated the attempt. In the same
      cohort, the frequency of suicidal attempts dropped by 50% among women and rose by
      125% among men compared to the previous observation. In the personal history, the
      information both about emotional and physical deprivation during childhood was
      more frequent among persons with suicidal attempts. On the other hand, partners'
      characteristics as possible sources of daily stress situations were not different
      between groups. Men with suicidal attempts were significantly more often heavy
      smokers (smoking more that 20 cigarettes daily) and alcohol abusers.
      Surprisingly, the level of satisfaction with family life was significantly higher
      in both sex groups with suicidal attempts. CONCLUSIONS: Although majority of
      respondents in all groups reported their health status as good, more detailed
      questions showed significantly higher frequency of different psychiatric
      disorders and moods in the groups of persons with suicidal attempts: irritation,
      exhaustion among men, anxiety, depression, dejection among women. Also subjective
      evaluation of parents' good health is not in correspondence with the relative
      high number of hospitalization (10% men and 40% women with suicidal attempts) and
      frequent using of psychoactive drugs. The psychic health of ELSPAC parents will
      be assessed in further prospective measurements.

PMID- 19177736
TI  - [Pregnancy and delivery in type II hereditary antithrombin deficient patients].
AB  - Antithrombin is a plasma protein that regulates haemostasis by inhibiting
      procoagulant serine proteases. Hereditary antithrombin deficiency is associated
      with an increased risk of venous thromboembolism. The risk of vessel occlusion
      escalates especially during the pregnancy due to hyperestrogen condition both in
      the maternal and in foetal circulation. Our case report describes a 24-years old
      gipsy-woman with severe congenital AT deficiency and recurrent foetal loss in her
      history. She informed us about her 4th pregnancy in the 12th gestation week
      therefore warfarin treatment and regular checking up INR was recommended. We
      didn't have any information about the pregnancy course till the 41st gestation
      week. When the patient came to give birth, the entry INR value was 1.0. She has
      delivered a healthy male newborn by caesarean section. Two weeks after delivery
      when effective INR value due to peroral anticoagulant therapy was achieved, she
      was released from the hospital and since that we have not seen her.

PMID- 19177737
TI  - [Treatment of hemosuccus pancreaticus by bilateral embolization of gastric
      arteries].
AB  - BACKGROUND: Arosion of peripancreatic arteries in acute or chronic pancreatitis
      is a rare cause of bleeding into gastrointestinal tract--hemosuccus pancreaticus.
      Aim of the paper is to show the diagnostic and therapeutic options in this
      serious clinical stage. METHODS AND RESULTS: We report a case of a patient with
      chronic pancreatitis who developed acute bleeding into the gastrointestinal tract
      due to the perforation of a pseudoaneurysm into pancreatic pseudocyst in the area
      of the pancreatic body. The diagnosis of hemosuccus pancreaticus, established by
      endoscopy and postcontrast CT examination, was confirmed by angiography. We
      stopped the acute bleeding from pseudoaneurysm, unusually well supplied by both
      gastric arteries by embolization of both arteries with metallic coils.
      CONCLUSIONS: Angiography plays an irreplaceable role in patients with hemosuccus
      pancreaticus. Our case demonstrates bleeding from pseudoaneurysm supplied by both
      gastric arteries, whose embolization produced an immediate hemostasis and
      improvment the patient's condition.

PMID- 19177738
TI  - [Czech medical doctors and year 1968].

PMID- 19177739
TI  - [Rediscovered Theodor Boveri and his dateless reflections on the development of
      malignancies].

PMID- 19177740
TI  - [Selman Abraham Waksman].

PMID- 19177741
TI  - Protection by Nigella sativa against carbon tetrachloride-induced downregulation
      of hepatic cytochrome P450 isozymes in rats.
AB  - Nigella sativa (family Ranunculaceae) is an annual plant that has been
      traditionally used on the Indian subcontinent and in Middle Eastern countries. In
      this study, we investigated the effect of N. sativa oil on the drug-metabolizing
      cytochrome P450 (CYP) enzymes and whether it has a protective effect against the
      acute hepatotoxicity of CCl4. Intraperitoneal injection of rats with CCl4
      drastically decreased CYP2E1, CYP2B, CYP3A2, CYP2C11, and CYP1A2 mRNA and protein
      expressions. Oral administration of 1 ml/kg N. sativa oil every day for one week
      prior to CCl4 injection alleviated CCl4-induced suppression of CYP2B, CYP3A2,
      CYP2C11, and CYP1A2. Moreover, CCl4 increased iNOS and TNFalpha mRNA, while N.
      sativa oil administration for one week prior to CCl4 injection downregulated the
      CCl4-induced iNOS mRNA and up-regulated IL-10 mRNA. These results indicate that
      N. sativa oil administration has a protective effect against the CCl4-mediated
      suppression of hepatic CYPs and that this protective effect is partly due to the
      downregulation of NO production and up-regulation of the anti-inflammatory IL-10.

PMID- 19177742
TI  - Polymorphism in MRL and AKR mice Sry: a candidate gene for the appearance of
      testicular oocyte.
AB  - Although mammals produce either sperm or eggs depending on their sex, newborn
      MRL/MpJ male mice contain oocytes within their testes. In our previous study, the
      testicular oocyte appears as early as day 0 afterbirth and has morphological
      characteristics as an oocyte such as zona pellucida and follicular epithelial
      cells. Based on the observation of F1 between MRL/MpJ and C57BL/6, one of the
      genes causing the appearance of testicular oocyte exists on the Y chromosome. In
      the present study, we found testicular oocytes within newborn AKR mice. Wehave
      also analyzed the Sry genes from several inbred mouse strains and identified a
      shortened glutamine repeat near the C-terminal region that is unique to MRL and
      AKR. These results suggest that polymorphism of glutamine repeat within SRY
      correlates with the appearance of testicular oocyte and this phenotype is derived
      from AKR, one of the original strains of MRL mice.

PMID- 19177743
TI  - Immunohistochemical localization of the estrogen receptor alpha (ERalpha) and
      progesterone receptor (PR) in the uterus of sika deer (Cervus nippon) during
      pregnancy.
AB  - Information on steroid hormone receptor distribution in the uterus is essential
      to understand the roles of their ligands in pregnancy. This study examined the
      spatio-temporal localization of estrogen receptor alpha (ERalpha) and
      progesterone receptor (PR) in the uterus of sika deer (Cervus nippon) to
      determine the estrogen and progesterone action site during pregnancy. Ovaries and
      uteri were collected from 21 pregnant sika deer with single fetus and two corpora
      lutea, ranging from Day 20 to Day 207 of pregnancy. In addition, genital organs
      were also collected from three sika deer whose gestational status was unknown:
      one female had only one developing corpus luteum: < or = Day 4 (metestrus) and
      two females had two corpora lutea, one of which was at the developing stage
      equivalent to diestrus or early pregnancy: > Day 7 (diestrus). Staining of
      ERalpha and PR was clear in all cell types during metestrus. During diestrus, the
      presence of ERalpha was also clear in deep glandular epithelium, stroma and
      myometrium, whereas it was suppressed in luminal epithelium and shallow glandular
      epithelium. Staining of PR was suppressed in luminal epithelium but was
      detectable in other cell types. Staining of ERalpha in all cell types and PR in
      luminal epithelium and glandular epithelium became undetectable by Day 28. PR was
      presented in stroma and myometrium throughout pregnancy. The distribution pattern
      of ERa and PR was different during diestrus from that in a ruminant. This could
      be attributed to estrogen secretion from the maturing and ovulating follicles in
      the presence of developed corpus luteum.

PMID- 19177744
TI  - Genetic and antigenic analyses of a Puumala virus isolate as a potential vaccine
      strain.
AB  - Puumala virus (PUUV), a causative agent of hemorrhagic fever with renal syndrome
      (HFRS), is prevalent in Europe and European Russia. No vaccine has been developed
      for PUUV-associated HFRS, primarily because of the low viral yield in cultured
      cells. A PUUV strain known as DTK/Ufa-97 was isolated in Russia and adapted for
      growth in Vero E6 cells maintained in serum-free medium. The DTK/Ufa-97 strain
      produced a higher viral titer in serum-free medium, suggesting that it may prove
      useful in the development of an HFRS vaccine. When PUUV-infected Vero E6 cells
      were grown in serum-free medium, the DTK/Ufa-97 strain yielded more copies of
      intracellular viral RNA and a higher viral titer in the culture fluid than did
      the Sotkamo strain. Phylogenetic analysis revealed that PUUVs can be classified
      into multiple lineages according to geographical origin, and that the DTK/Ufa-97
      strain is a member of the Bashkiria-Saratov lineage. The deduced amino acid
      sequences of the small, medium, and large segments of the DTK/Ufa-97 strain were
      99.2% to 100%, 99.3% to 99.8%, and 99.8% identical, respectively, to those of the
      Bashkirian PUUV strains and 96.9%, 92.6%, and 97.4% identical, respectively, to
      those of the Sotkamo strain, indicating that the PUUVs are genetically diverse.
      However, DTK/Ufa-97 and other strains of PUUV exhibited similar patterns of
      binding to a panel of monoclonal antibodies against Hantaan virus. In addition,
      diluted antisera (i.e., ranging from 1:160 to 1:640) specific to three strains of
      PUUV neutralized both homologous and heterologous viruses. These results suggest
      that the DTK/Ufa-97 strain is capable of extensive growth and is antigenically
      similar to genetically distant strains of PUUV.

PMID- 19177745
TI  - [Mucosal immune defense against sexually transmitted diseases].

PMID- 19177746
TI  - [Status and future of sexually transmitted diseases in Japan].
AB  - According to the results of the fixed-point survey, the incidence of both genital
      chlamydial infection and gonococcal infection has tended to decrease since 2003
      in Japan. This trend has been more marked in young persons of both sexes.
      However, it has been suggested that the fixed-point survey has a problem with
      respect to the method of selecting designated medical institutions for
      notification. Moreover, it should be remembered that there are many patients
      without symptoms in addition to patients with symptomatic sexually transmitted
      diseases. We performed a group study of patients with asymptomatic sexually
      transmitted diseases over 3 years. As a result, it was confirmed that the
      prevalence of asymptomatic genital chlamydial infection was highest among female
      high school students aged 16-18 years, and was approximately 5% even among
      healthy men in their twenties. Based on these results, to prevent the spread of
      sexually transmitted diseases in the young, it seems necessary to perform large
      scale screening for these diseases(especially in young persons) and establish a
      system that allows the results of screening to ensure early detection and
      treatment of sexually transmitted diseases.

PMID- 19177747
TI  - [Epidemiology of sexually transmitted diseases in Japan--its international
      characteristics].
AB  - Japan has witnessed the rise of STDs, and the increase in the number of HIV cases
      infected through sexual contact in the last decade. Background of these trends
      will be the exceptionally high prevalence of paid sex in Japan among developed
      countries and the diversified unprotected sexual behaviors that have prevailed
      among general population since 1990s. STDs are also increasing and HIV infection
      through sexual contact has resumed to increase among other developed countries in
      the same period of time. Coordinated research among developed countries is
      becoming increasingly important to clarify the specific and general causes of
      such phenomena and thus to explore the possibility of coordinated responses
      toward these global challenges.

PMID- 19177748
TI  - [Guidelines on the diagnosis and treatment of sexually transmitted diseases].
AB  - Guidelines for the diagnosis and treatment of sexually transmitted diseases (STD)
      have been revised and updated from 1996 in Japan. Revision will be made in the
      whole content of 2008 version and it will be published in the nearest months. In
      the diagnosis of gonococcal and chlamydial infection, newer nucleic acid
      amplification test kit (NAAT), Aptima Combo2 and Probetek ET, was developed and
      recommended to use. Diagnosis and treatment of gonococcal infection is
      problematic because of increase of pharyngeal infection and increase of resistant
      strains against many of antimicrobial agents. Modified Thayer-Martin culture
      medium or newer NAATs should be used in the diagnosis of pharyngeal gonococcal
      infection, and single 1 g dose of ceftriaxone should be used in the treatment of
      gonococcal infection including pharyngeal infection. In young students, increase
      of chlamydial infection is now main problem in Japan. Screening of chlamydial
      infection by using NAATs should be done. Much of clinical research to know the
      proper diagnosis and treatment of STD should be done to verify the evidences
      described in the guidelines and to make new evidences in the near future.

PMID- 19177749
TI  - [Testing services for sexually transmitted infections in Japan, public funding
      for HIV testing compared to public funding for other STI testing].
AB  - HIV and other STIs testing services of public funded setting have not been
      integrated in Japan. Public health centers and other public funded testing sites
      provide free anonymous HIV test. This has been playing an important role to
      confirm almost half of asymptomatic patients. Early diagnosis is an essential
      intervention for personal health, and critical for preventative strategies of
      public health. However, the role of public health centers and other public funded
      testing sites are very limited for other STIs. The symptomatic patients visit
      private clinic/hospital for diagnosis and treatment, but it is difficult for
      asymptomatic person to visit such medical facilities. The prevalence of genital
      chlamydia in young women in Japan remains very high compared to other developed
      countries. So, I think public funding of testing for genital chlamydia and other
      asymptomatic STIs should be expanded and integrated with HIV testing programs in
      Japan. Recently, there is the problem of the shortage of OB/GY doctors and
      clinics. This might influence the accessibilities of STIs testing and treatment
      opportunities for women. This is a new problem of STI testing in Japan.

PMID- 19177750
TI  - [Structure and molecular mechanisms of infection and replication of HIV].
AB  - Studies on molecular structure and mechanisms of replication of a pathogen are
      important from both scientific and clinical viewpoints. The replication study
      allows us to identify key molecules to regulate life cycle of the pathogen and to
      screen rationally anti-pathogen drugs. The structural study helps understand how
      the key molecules work at atomic levels and to design adequately the drugs. In
      this article, we review important findings on structural and replication studies
      of human immunodeficiency virus (HIV). We also summarize the latest methods for
      the structural study, mainly focusing on computational simulation technology (in
      silico analysis). Finally, we summarize briefly standard methods to study
      replication of viruses.

PMID- 19177751
TI  - [Molecular mehanisms of drug resistance acquisition in HIV].
AB  - The advent of highly active antiretroviral therapy has greatly improved the
      prognosis of HIV-1 infection, but eradication of the virus has not been achieved.
      The emergence of antiretroviral-resistant viruses is one of the most important
      factors affecting the prognosis of HIV-1 infected patients today. In this
      manuscript, recent progresses in drug resistance HIV researches are reviewed. As
      for the acquisition of nucleoside analogue RT inhibitor resistance, excision
      mechanism is more clear by enzymological and structural view points. Recently
      developed integrase inhibitor, the whole new target of antiretroviral, induces
      drug resistance mutations in the active sites of integrase. The first drug that
      targets the host factors, chemokine receptor CCR5, demonstrates different
      resistance profiles from the present antiretrovirals. These new findings are
      important to develop successful treatments that will not fail due to drug
      resistance acquisition.

PMID- 19177752
TI  - [Mechanisms of high-risk human papillomavirus-induced cervical carcinogenesis].
AB  - Human papillomaviruses (HPVs) are believed to be the primary causal agents for
      development of pre-neoplastic and malignant lesions of the uterine cervix and
      high-risk types such as type 16 and 18 are associated with more than 90% of all
      cervical carcinomas. The E6 and E7 genes of HPVs are thought to play causative
      roles, since E6 promotes the degradation of p53 through its interaction with
      E6AP, an E3 ubiquitin ligase, whereas E7 binds to the retinoblastoma protein pRb
      and disrupts its complex formation with E2F transcription factors. Although
      prophylactic vaccines have become available, it is still necessary to clarify the
      mechanisms of HPV-induced carcinogenesis because of the widespread nature of HPV
      infection. In this article, the mechanisms of high-risk HPV E6 and E7-induced
      multistep carcinogenesis and recently identified functions of these oncoproteins
      are reviewed.

PMID- 19177753
TI  - [Development of an HPV vaccine--remaining issues and perspective].
AB  - Cervical cancer, the second most frequent gynecological malignancy in the world,
      is caused by infection with one of the 15 types of high-risk HPVs. Vaccines
      protecting women from infection with high-risk HPVs can reduce prevalence of
      cervical cancer. At present, two prophylactic vaccines (GlaxoSmithKline
      "Cervarix" and Merck "Gardasil") have been approved by several countries. These
      vaccines can almost completely protect HPV16 and 18 infections which account for
      approximately 50% and 20% of cervical cancer, respectively. However, cervical
      cancer screening should continue in all vaccinated women due to exposure of the
      other oncogenic HPV types. There are also unanswered remaining questions about
      overall vaccine effectiveness, duration of protection, and adverse effect.

PMID- 19177754
TI  - [Recent progress in diagnostic test of sexually transmitted disease].
AB  - In Japan, STD has widely spread especially in big cities and number of infected
      people have been increasing with HIV infection. Clinicians have to diagnose,
      treat STDs appropriately and educate the patients to cease the new infection. So
      I want to review how to use these tests as a screening or more specific
      situation.

PMID- 19177755
TI  - [Advancements in diagnosis of sexually transmitted diseases in urology].
AB  - Sexually transmitted diseases diagnosed and treated exclusively in urology
      clinics are male urethritis and epididymitis caused by Neisseria gonorrhoeae and
      Chlamydia trachomatis. Although recent developments in diagnostic tools have made
      it possible to detect these microorganisms with extremely high sensitivities, the
      screening of Neisseria gonorrhoeae using the microscopic observation of
      intraleucocyte diplococci stained by methylene blue or gram staining in the first
      voided urine sediment or urethral smears still the key point in the diagnosis and
      treatment of gonococcal urethritis. In recent years, mycoplasmas and ureaplasmas
      have been supposed to be possible pathogens of prostatitis as well as urethritis.
      The objective diagnosis of genital skin lesions caused by herpes simplex virus
      and human papillomavirus are remained to be developed.

PMID- 19177756
TI  - [Diagnosis of HPV-related diseases].
AB  - The STD including HPV infection has been worldwide spread in young persons. HPV
      has been recognized as a necessary cause of cervical cancer. It is highly
      prevalent sexually active persons and traceable in its natural history with a
      recent advanced technology. This technology has provided the basis of improved
      cervical cancer screening and management protocol. It has also been shown that
      the major virion protein of HPV alone, once replicated in convenient expression
      system, produces immunogens that are able to induce powerful immune responses.
      Now, HPV-related diseases can be prevented by the HPV-vaccines which are
      commercially available.

PMID- 19177757
TI  - [Diagnosis of sexually transmitted infection in dermatology].
AB  - A lot of disorders of the sexually transmitted infection presents cutaneous
      manifestations. There are a systemic cutaneous symptom to develop as a result of
      pathogen which invades the body through the lymph node and blood vessels and
      immune response, and a localized cutaneous symptom to appear in the part where
      pathogen was infected with directly reactively. We showed diagnostic procedure of
      the STI that a symptom was present in skin.

PMID- 19177758
TI  - [Diagnosis of sexually transmitted diseases in pediatrics].
AB  - Sexually transmitted diseases(STD) among children includes the following three
      infections; vertical transmissions from infected mothers to newborns and infants,
      infections among adolescents, and infections in victims of sexual abuse.
      Detection of STD organisms from children suggests presence of sexual abuse.
      Diagnostic procedure of STD among children needs to be less invasive. Antigen
      detection tests and PCR methods for some STD organisms may show false positive
      results. Normal flora of genital organs of children should also be noticed for
      diagnosis of STD. Vertical infections of STD organisms cause a variety of
      symptoms to infected children. Diagnosis of infections in children using
      commercially available reagents should be cautious. Flora of respiratory tracts
      and transplacental antibody may affect the results.

PMID- 19177759
TI  - [STD in the eye].
AB  - In this paper, we review sexually transmitted diseases (STD) involving the eye.
      Recently conjunctivitis due to Chlamydia trachomatis in children and adults is
      increasing, and that of Neisseria gonorrhoeae resistant to multiple antibiotics
      has attracted special attention in our country. Syphilis has many ocular
      manifestations such as keratitis, iridocyclitis, retinochorioiditis, and
      neuritis, etc. Ocular complications related to HIV infection, including HIV
      retinopathy, cytomegalovirus retinitis, zoster ophthalmics, and Kaposi s sarcoma
      in conjunctiva are increasing in Japan. Phthirus pubis infection of the eye lid,
      and human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis are
      occasionally reported. Furthermore conjunctival tumor associated with human
      papilloma virus (HPV) infection, acute retinal necrosis(ARN) due to herpes
      simplex virus type 2 (HSV-2), as well as hepatitis B virus (HVB) and hepatitis C
      virus (HVC) retinopathy are also mentioned in this review.

PMID- 19177760
TI  - [HIV infection/AIDS].
AB  - HIV infection is known as one of sexually transmitted infection and number of new
      HIV-infected patients is increasing in Japan. It' s still difficult to detect HIV
      infected career because HIV career has no symptoms for several years after HIV
      infection. HIV treatment is progressing and made HIV-infection controllable
      disease, although HIV can not be eradicated from body. This therapy is needed
      life-long continuance because HIV can easily achieve mutation that decrease
      efficacy of antiretroviral drugs. Thus, we should perform HIV screening test more
      actively to prevent the further spread of infection and if detected, must educate
      importance of adherence of therapy.

PMID- 19177761
TI  - [Genital chlamydial infection].
AB  - Genital chlamydial infection is a sexually transmitted disease (STD) of public
      health importance. Infection with Chlamydia trachomatis can cause urethritis,
      cervicitis, pharyngitis, or epididymitis, although asymptomatic infections are
      quite common. Chlamydial infection remains asymptomatic in approximately 50% of
      infected men and 70% of infected women. Genital infection with C. trachomatis
      markedly enhances the risk for reproductive tract sequelae in women, including
      tubal factor infertility and ectopic pregnancy. A proper detection of C.
      trachomatis and its treatment is of importance to prevent outbreaks of genital
      chlamydial infection. We review the pathology, diagnosis and treatment of this
      entity.

PMID- 19177762
TI  - [Neisseria gonorrhoeae infections].
AB  - Neisseria gonorrhoeae infections are common bacterial sexually transmitted
      diseases. Men will usually experience lower urinary tract symptons attributed to
      urethritis, epididymitis, proctitis, or prostatitis, with associated mucopurulent
      urethral discharge. Many women are asymptomatic. But, occasionally, they have
      symptons of vaginal and pelvic discomfort of dysuria, and these infections can
      lead to pelvic inflammatory disease. Recentry, high prevalence of Neisseria
      gonorrhoeae isolates resistant to antimicrobial agents is a serious problem in
      the treatment of gonorrhea. For example, in Fukuoka city, Japan, the proportion
      of the isolates resistant to ciprofloxacin (CPFX) were 73.4% in 2006 and it was
      still so high. The proportion of the isolates resistant to tetracycline (TC) was
      38.5% in 2006 and that of isolates resistant to penicillin G (PCG) was 17.5%.
      Owing to this high prevalence of antimicrobial-resistant Neisseria gonorrhoeae in
      Japan, the clinical efficacy rates of oral antimicrobial agents have become
      lower. So, as first-line therapy for gonococcal infections, only three parenteral
      regimens of single doses of ceftriaxone, cefodizime or spectinomycin are
      recommended by the Japanese Society for Sexually Transmitted Diseases. In the
      circumstances, we studied in vitro activity of combinations of oral agents such
      as, beta-lactam and azithromycin, fluoroquinolone and azithromycin, or beta
      lactam and fluoroquinolone against Neisseria gonorrhoeae. The
      cefixime+azithromycin combination demonstrated greater synergy than other
      combinations.

PMID- 19177763
TI  - [Syphilis].
AB  - In Japan, the incidence of syphilis has decreased, and clinicians might be more
      likely to overlook syphilis than before. We show typical clinical manifestations
      and treatment of syphilis for clinicians unfamiliar with the disease and
      emphasize that two types of serologic test, non treponemal tests and specific
      treponemal tests, are essential for diagnosis of syphilis. Recent automated
      serologic tests for syphilis are useful to examine patients' progress after they
      are treated. The early stage of syphilis is gradually spreading among men in
      Japan, and HIV coinfections are often caused by homosexual contacts. We present a
      sample figure in the classic medical book, "Atlas of syphilis and the venereal
      diseases".

PMID- 19177764
TI  - [Genital herpes].
AB  - Genital herpes (GH) is the second leading cause of sexual transmitted disease in
      women and the third in men. About 40% of female genital herpes is caused by
      herpes simplex virus type 1 (HSV-1) and the remaining by type-2 (HSV-2). Fifty
      four percent of primary female GH was caused by type-1, whereas 86% of recurrent
      cases by type-2. For rapid diagnosis of GH, LAMP(loop-mediated isothermal
      amplification), HSV DNA nuclear amplification method developed in Japan, was
      applied and favorable results were obtained. We compared three gG based type
      specific antibody kits (Platteria, HerpeSelect and Captia). Among these,
      Platteria was shown to be most sensitive and specific.

PMID- 19177765
TI  - [Condyloma acuminatum].
AB  - Condyloma acuminatum is a sexually transmitted disease caused by human
      papillomavirus infection, especially HPV DNA types 6 and 11. Its appearance is
      distinctively papillary and it can be diagnosed by careful observation of its
      particular appearance. The treatment for condyloma acuminatum is generally
      classified into surgical and medical therapies. In Japan, imiquimod has finally
      been approved and can be prescribed in the clinical situation. Treatment with 5%
      imiquimod cream is highly effective and noninvasive compared with surgical
      therapy. We anticipate that imiquimod will contribute to efficient control of the
      disease in the future.

PMID- 19177767
TI  - [Trichomoniasis].
AB  - Trichomonas vaginalis is the most common curable sexually transmitted disease
      worldwide. In spite of serious health sequelae including facilitation of HIV
      transmission, PID, and adverse outcomes of pregnancy, it remains an
      underestimated condition, as a half of female infections and the majority of male
      infections are asymptomatic. T. vaginalis infection was not restricted in high
      risk groups, so screening or empiric treatment of low-risk groups should be
      considered. To develop diagnostic tests which is valuable like PCR and cheap like
      wet mount microscopy, and the targeted screening of asymptomatic patients will
      allow a large understanding of T. vaginalis epidemiology and raises concern about
      the impact of HIV transmission and female reproductive health. T. vaginalis can
      no longer be ignored.

PMID- 19177766
TI  - [Genital candidiasis].
AB  - Genital candidiasis occurs mainly in women referred as vulvovaginal candidiasis
      (VVC), and occasionally occurs in men as to be called balanitis. VVC is one of
      the most common causes of infectious vaginitis. Approximately three-quarters of
      women will experience an episode of VVC at least once in their life and 5-8% of
      them will have more than four attacks within a year; this condition has been
      designated as recurrent VVC (RVVC). Causative agent in majority of VVC is Candida
      albicans, but occasionally VVC is caused by other Candida spp. VVC is not
      traditionally considered a sexually transmitted disease. On occasion sexual
      transmission of Candida can occur during vaginal intercourse. Particularly
      Candida transmission and sexual behaviors are linked to RVVC. Epidemiological
      evidence suggests that anogenital and, especially, orogenital contact transmits
      Candida.

PMID- 19177768
TI  - [Non-chlamydial non-gonococcal urethritis].
AB  - Besides Chlamydia trachomatis, various microorganisms could cause non-gonococcal
      urethritis (NGU). Recently, Mycoplasma genitalium and Ureaplasma urealyticum
      (biovar 2) have been suggested to be other pathogens of NGU independent of C.
      trachomatis. Clinical findings of non-chlamydial NGU, including M. genitalium--or
      U. urealyticum-postive NGU, are not different from those of chlamydial NGU. M.
      genitalium and U. urealyticum (biovar 2) are susceptible to tetracyclines,
      macrolides, and fluoroquinolones. However, the post-treatment presence of M.
      genitalium in the urethra is significantly associated with persistent or
      recurrent urethritis. Eradication of this mycoplasma from the urethra is
      essential for managing M. genitalium-positive NGU. In treatment of non-chlamydial
      NGU, therefore, the antimicrobial agents that are active against M. genitalium
      should be chosen.

PMID- 19177769
TI  - [Pharyngeal Neisseria gonorrhoeae and Chlamydia trachomatis infections].
AB  - Oral sex is recently becoming a general sexual behavior among the youths in this
      country. Oral sex is often performed without a condom because they do not have to
      worry about pregnancy in oral sex. Chlamydia trachomatis and Neisseria
      gonorrhoeae which are sexually transmitted diseases are infected with not only
      the genital tract but also the pharynx. Oral sex attracts attention as a new
      route of infection of Chlamydia trachomatis and Neisseria gonorrhoeae. It is very
      imoportant that gential Chlamydia and gonococcal infections should be detected
      early and treated to protect from re-infection, because these infections are
      causes of infertility. If Chlamydia trachomatis and Neisseria gonorrhoeae are
      detected from a genital tract in a youth, pharyngeal Chlamydia trachomatis and
      Neisseria gonorrhoeae examinations should be performed.

PMID- 19177770
TI  - [STD and mother to child transmission].
AB  - Sexually transmitted disease (STD) is the disease that is spread by sexual
      contact, including chlamydial infection, gonorrhea, genital warts, herpes,
      syphilis, and infection with human immunodeficiency virus (HIV). STDs are the
      most common contagious diseases among young people in Japan. People with an STD
      may not have any symptoms and may not know they have it. Even if there are no
      symptoms, their health can be affected. Advanced STDs can cause severe damage to
      body. Often, symptoms occur only if the disease becomes more advanced. Untreated
      chlamydia or gonorrhea can cause pelvic inflammatory disease (PID) in women. PID
      is an infection of the uterus, fallopian tubes, and ovaries. It can cause
      infertility and ectopic pregnancy. If patient who has STD is pregnant, it can
      cause abortion, premature delivery and intrauterine infection.

PMID- 19177772
TI  - [To prevent the spread of STDs].
AB  - (1) It is very important thing to find general STDs, such as chlamydia infection
      in the early stage, because this can stop the spread of HIV/AIDS. (2) If patients
      are suffering from vaginal discharge, bleeding, lower abdominal pain, and/or
      urinary symptoms, we highly recommend that they need to take STD tests. (3) If
      some one whose first experiences of sexual intercourse were under 14, their
      behavior may have been related with their home environment. We have to know their
      problems at home. (4) Self-esteem is the basic factor for performing dual
      protection.

PMID- 19177771
TI  - [Sterility and STD].
AB  - About one million Chlamydia trachomatis urogenital infections occur in Japan.
      Infections of Chlamydia trachomatis or gonococci are associated many clinical
      syndromes, ranging from urethritis and epididymitis in men to cervicitis,
      salpingitis, acute urethra syndrome, endometritis, ectopic pregnancy, infertility
      and pervic inflammatory disease in women. Unfortunately early infected symptoms
      are often very mild or absent among women. So early diagnosis and treatment are
      both important in Chlamydia trachomatis and gonococci infection in women.
      Chlamydial and gonococcal infection are highly prevalent in young sexually active
      adolescent. With sexually active teens practicing high-risk behavior, frequent
      testing is ideal and offers multiple opportunities for education and counseling
      by the care workers.

PMID- 19177773
TI  - [Human health sciences].
AB  - Medical science and medical practice developed remarkably and economic conditions
      progressed so much in recent years in Japan. As the result, the average span of
      life of the Japanese is now the longest in the world and we are well off. The
      matter of the greatest concern of Japanese people at present is health. In fact,
      health foods, TV program on health and various matters concerning health overflow
      around us. It is fairly difficult to define health clearly and correctly. So long
      as anyone who wants to be in good health, he must be well physically and
      mentally. It is necessary to pursue the true health, and to investigate theories
      and techniques to obtain and concrete it, which is called human health sciences.

PMID- 19177774
TI  - [Examination of beneficial effects of risedronate in improving quality of life
      during long-term treatment of primary osteoporosis].
AB  - BACKGROUND AND AIMS: Risedronate is a first-line medication in the therapy of
      osteoporosis and a substantial amount of evidence has already established the
      clinical efficacy of risedronate in the treatment of osteoporosis. However,
      studies addressing its long-term efficacy in improving patients' quality of life
      (QOL) are rare. The aim of this study was to evaluate the therapeutic effect of
      long-term treatment with risedronate on the time-course of changes in patients'
      QOL. METHODS: Fourteen Japanese outpatients with primary osteoporosis (mean age:
      69.4 +/- 10.1 yr, 7 men and 7 women), who had continued treatment with oral
      risedronate alone (2.5 mg, daily) for more than 3 years as of July 2008, were the
      subjects of this study. We investigated the time-course of changes in patients'
      QOL using the Japanese Osteoporosis Quality of Life Questionnaire (JOQOL) of the
      Japanese Society for Bone and Mineral Research, together with measurement of bone
      mineral density and bone metabolic markers over 3 years. RESULTS: Risedronate
      significantly improved the total JOQOL score from 119.0 (103.0-127.0) points at
      entry to 128.0 (119.0-142.0) points at 12 months into the study (p=0.029) and
      this improvement was maintained during the study period. In addition, the pain
      score and the falls and anxiety score of the JOQOL continued to show significant
      improvements over 12 and 24 months, respectively. Serum BAP and NTX levels were
      significantly decreased at 6 months and continued to improve significantly during
      the study. We found no new bone fractures during the three study years and bone
      mineral density was maintained at good levels during the study period. The usage
      of cold or hot packs gradually decreased during the study period and was
      significantly reduced after 24 months (p=0.018). CONCLUSION: This study showed
      that long-term treatment with risedronate significantly improved and favorably
      maintained the QOL of patients with primary osteoporosis, particularly pain
      related scores.

PMID- 19177775
TI  - [Types and characteristics of macrolides].
AB  - Macrolide antibiotics have been used to treat acute and chronic inflammation in
      the respiratory tract based on their antibacterial activity. Now it is well known
      that macrolides down-regulate damaging prolonged inflammation as well as increase
      mucus clearance and decrease bacterial virulence. Some drug interactions with
      macrolides have been documented in clinical trials mainly connected with their
      influence on liver function. Adverse reactions are few and self-limited when used
      at the recommended dosage.

PMID- 19177776
TI  - [Immunomodulatory properties of macrolides].
AB  - Airways have a highly sophisticated immune defense system, so an excessive or
      inappropriate inflammatory response can result in development of numerous
      complications of respiratory tract diseases. During inflammation, due to
      increased metabolism of various immune system cells, free oxygen radicals and
      other chemical compounds are produced, which enhance oxidative stress, playing an
      important role in the pathogenesis of numerous pulmonary diseases, such as
      bronchial asthma, cystic fibrosis or COPD. Influence of antibiotics, not related
      to their bactericidal or bacteriostatic properties, on activity of the immune
      system is the subject of numerous studies and controversies. Immunomodulatory
      effect of antibacterial drugs can pose an additional therapeutic benefit, but
      also can cause an undesirable modification of immune processes as a result of
      hampering cell immunity or promoting an inflammatory response. It is thought that
      numerous antibiotics and chemotherapeutics can exert a nonspecific influence on
      inflammation activity, and such effect can be positively related to the
      concentration of a particular drug in immune system cells, especially in
      neutrophils. In some researches immunomodulatory effect of macrolides has been
      proven. The review presents current knowledge on the modulating properties of
      macrolides and possibilities of making use of theirs in a treatment of the lung
      diseases.

PMID- 19177777
TI  - [Atypical bacteria in respiratory tract infections --pathogenesis and diagnosis].
AB  - Atypical bacteria, including Mycoplasma pneumoniae, Chlamydophila pneumonia and
      Legionella pneumophila play significant role in respiratory tract infections and
      account for 40% of all cases of community acquired pneumonia (CAP). These
      organisms also commonly occur as co-pathogens in mixed infections with mortality
      rates as high as 25%. The biological mechanisms and diagnosis of atypical
      infections is presented in this study.

PMID- 19177778
TI  - [Upper respiratory tract infections in children caused by atypical bacteria].
AB  - It encounters despite solid progress in development of diagnostic methods
      diagnostics the diseases of upper respiratory tract and ears in children called
      out by atypical bacteria's on the ground clinical symptoms and their treatment is
      difficulty still. AIM: The performance of accessible review of current literature
      was on the aim of work opinion of the atypical bacteria's part in evocation the
      infections the upper respiratory tract and ears in children, and performance of
      characteristic symptoms of clinical diseases these organs the bacteria's also.
      CONCLUSIONS: The quoted in work results of investigations do not it let on the
      unambiguous opinion the atypical bacteria part in contagions of infections the
      upper respiratory tract and ears in children. It seems however, that Mycoplasma
      pneumoniae answers first of all for evocation the acute infections of upper
      respiratory tract; however Chlamydophila pneumoniae plays the larger part in
      illnesses chronic as well as co-existent pathogen in illnesses sharp. Atypical
      bacteria can cause upper respiratory tract infections significantly more often
      than previously thought. These infections often occur in patients with history of
      respiratory recurrences.

PMID- 19177779
TI  - [Azithromycin in the therapy of lower respiratory tract infection in children].
AB  - Lower respiratory tract infections are serious health problem in pediatric
      population. The prevalence of infections is the highest in the youngest group and
      typical bacteria is the most common cause of diseases in this group. The role of
      atypical pathogens is on the rise in older patients. The choice of therapy
      depends on ethiology The article is focused on the role of azithromycin showing
      the benefits of such therapy.

PMID- 19177780
TI  - [Upper respiratory tract infection in adults caused by atypical bacteria].
AB  - Atypical bacteria play role in infection of upper respiratory tract in adults.
      The most often bacteria playing role in these infections are Chlamydophila
      pneumioniae and Mycoplasma pneumoniae. These bacteria have significant impact in
      pharyngitis and tonsillitis and less in rhinosinusitis. Atypical bacteria can
      cause infection of the upper respiratory tract as a single pathogen or one of the
      pathogens. Mycoplasma pneumoniae most often is s a single causal factor of the
      disease, when Chlamydophila pneumoniae most often co-exists with infection with
      other pathogens. Majority of infections of upper respiratory tract in adults
      caused by atypical bacteria has mild history with insignificant sings and
      symptoms. Suspicion of the disease can be recurrent history of disease or absence
      of recovery after standard treatment.

PMID- 19177781
TI  - [Lower tract infections as potential indication for therapy with macrolides].
AB  - Community acquired pneumonia (CAP) is the sixth leading cause of death. Atypical
      pneumonia caused by Mycoplasma pneumoniae, Chlamydophila pneumoniae and
      Legionella pneumophila accounts for up to 40% of all cases of CAP. Atypical
      pneumonia due to Mycoplasma and Chlamydophila usually cause milder forms of
      pneumonia and are characterized by a more drawn out course of symptoms unlike
      other forms of pneumonia which can come on more quickly with more severe early
      symptoms. Mycoplasma pneumonia often affects younger people and may be associated
      with symptoms outside of the lungs (such as anemia and rashes), and neurological
      syndromes (such as meningitis, myelitis, and encephalitis). Severe forms of
      Mycoplasma pneumonia have been described in all age groups. Chlamydophila
      pneumonia occurs year round and accounts for 5-15% of all pneumonias. It is
      usually mild with a low mortality rate. In contrast, atypical pneumonia due to
      Legionella accounts for 2-6% of pneumonias and has a higher mortality rate.
      Elderly individuals, smokers, and people with chronic illnesses and weakened
      immune systems are at higher risk for this type of pneumonia. Contact with
      contaminated aerosol systems (like infected air conditioning systems) has also
      been associated with pneumonia due to Legionella. All of known macrolides,
      including azythromycin and clarythromycin, have excellent activity against the
      atypical respiratory pathogens. The are primarily bacteriostatic, by binding to
      the 50S subunit of the ribosome, they inhibit bacterial protein. The potential
      indications for treatment lower respiratory tract infections with macrolides were
      presented in this study.

PMID- 19177782
TI  - [The macrolide antibiotics in treatment of skin diseases].
AB  - The macrolide antibiotics are widely used in various skin diseases treatment.
      Mainly their bacteriostatic properties and Gram-positive and some Gram-negative
      bacteria wide spectrum of efficiency is mainly used in dermatology. Macrolides
      have also anti-inflammatory and immuno-modulating properties, therefore can be
      used among others in atopic dermatitis therapy. The study shows characteristic
      and recommendations for application of most popular macrolide antibiotics with
      special emphasis on safety and rational usage, due to possibility of selection of
      resistant bacteria strains.

PMID- 19177783
TI  - [Clinical basis of macrolides apply in diseases of the respiratory tract].
AB  - Macrolides are applied to control bacterial infection of the respiratory tract.
      Because of their possibility to penetrate into bacterial cell, they are used in
      inflammatory diseases caused mainly by atypical bacteria. Many macrolide
      gidelines have been accepted for antibiotic therapy. In the paper recommendations
      for macrolide treatment have been based on Polish results of bacterial resistance
      in pneumonia, asthma and COPD exacerbations, sinusitis and otitis.

PMID- 19177784
TI  - [Antibiotic pharmacoeconomics].
AB  - Today more than ever, doctors in the ambulatory care and hospitals must
      effectively manage the use of antibiotics to control costs and preserve their
      usefulness. To achieve this goal, antibiotic management must evolve from
      simplistic antibiotic cost containment to more complex, appropriate use program
      that are founded on clinical outcomes-based pharmacoeconomic analyses. The
      successful application of pharmacoeconomic principles to antimicrobial therapy
      requires maximizing therapeutic effectiveness while minimizing costs, with the
      primary on pharmacokinetic considerations. This article reviews the various
      pharmacoeconomic factors that affect antibiotic costs in relation to patients and
      institutions. Cost-effectiveness studies of macrolides in pulmonary infections
      are presented in this study to illustrate the utility of these analyses.

PMID- 19177785
TI  - [Microalbuminuria, a universal marker of unfavourable prognosis].
AB  - The phenomenon of microalbuminuria formerly regarded solely as an early
      manifestation of hypertensive and diabetic nephropathy is presently believed to
      be an integral marker of poor prognosis due to the establishment of its
      importance as a sign of overall endothelial dysfunction. Risk factors of
      microalbuminuria, mechanisms of its development, prognostic value, and approaches
      to the elimination of this disorder are discussed.

PMID- 19177786
TI  - [Neuropathic and musculo-skeletal pain. Modern approaches to diagnosis and
      treatment].
AB  - Chronic pain syndromes comprise a heterogeneous group of very common clinical
      conditions having important medical and social implications. The author briefly
      reviews evolution of the concepts of mechanisms and characteristics of
      neuropathic, nociceptic, and psychogenic pain and current approaches to the
      diagnosis and treatment of neuropathic pain syndromes and musculo-skeletal pains.
      The recommended therapeutic modalities for patients with chronic pains are based
      on the results of original studies conducted in the Department of Neural
      Diseases, I. M Sechenov Moscow Medical Academy, during the last years and recent
      data obtained in foreign clinics.

PMID- 19177787
TI  - [On the problem of obesity in internal diseases].
AB  - A review of available data on epidemiology of obesity, its classification,
      physiological role and morphological structure of adipose tissue, effect of
      obesity on metabolic processes depending on fat distribution in the body. The
      influence of obesity on the function of cardio-vascular, respiratory, digestive,
      urinary, and endocrine systems is considered along with its role in the clinical
      picture and outcome of somatic diseases.

PMID- 19177788
TI  - [Importance of genetic polymorphism of cytochrome P450 isoenzymes for the choice
      and regimes of antidepressant and antipsychotic dosing on an individual basis].
AB  - Polymorphism of P450 2D6 (CYP2D6) gene is one of the causes of altered activity
      of enzymes controlling metabolism of medicinal products (MP), specifically
      increasing and decreasing biotransformation of xenobiotics. These changes result
      either in a rise or in a fall of plasma MP; in the former case adverse effects
      (AE) of MPs are likely to arise, in the latter xenobiotic therapy may prove
      inefficient. Drug interactions also contribute to variation of MP levels in
      plasma and undesirable changes of their pharmacological action that may require
      correction of the therapeutic regime. This paper presents results of original
      studies and reviews domestic and foreign publications on polymorphism of genes
      encoding isoenzymes involved in biotransformation processes, such as CYP2D6. This
      issue is of importance for psychiatric and psychosomatic practice. Algorithms for
      the rational choice of antidepressants and antipsychotics are proposed with a
      view to enhancing efficiency and safety of therapy with the use of these MPs.

PMID- 19177789
TI  - [Effect of radio and chemotherapy of malignant neoplasms on the development of
      atherosclerosis, coronary heart disease, and lipid spectrum].

PMID- 19177790
TI  - [External respiratory function and adrenal androgenic function in patients with
      bronchial asthma].
AB  - The aim of this study was to assess external respiratory function in patients
      with bronchial asthma (BA) and different serum levels of the adrenal androgen
      dehydroepiandrosterone sulfate (DHEAS). A total of 108 patients (59 women and 49
      men) of the mean age 38.8+/-13.4 years were involved. Most of them (62 or 57.4%)
      had a moderately severe disease. Endogenous, exogenous, and mixed forms of BA
      were diagnosed in 24 (22%), 27 (25%), and 57 (53%) respectively. Serum DHEAS and
      cortisol were assayed by ELISA. The DHEAS level was found to be significantly
      higher in men with BA than in women (2.08+/-0.9 mcg/ml and 0.95+/-0.8 mcg/ml
      respectively), p < 0.001, while serum cortisol was virtually identical. The DHEAS
      level in patients with exogenous BA was higher than in those with endogenous BA
      (2.0+/-0.7 and 1.2+/-0.5 mcg/ml respectively), p < 0.05. Cortisol levels did not
      significantly differ. Single-factor correlation analysis revealed negative
      correlation between DHEAS level and forced expiratory volume in 1 second (FEV1)
      (r = 0.53, p < 0.001) . Multifactor regression analysis demonstrated sex and age
      independent direct relationship between FEV1 and DHEAS (R2 = 0.60, beta = 0.38, p
      < 0.001). It is concluded that severe BA is associated with low serum DHEAS
      manifest as enhanced frequency and duration of asthmatic attacks. External
      respiratory function in BA patients with lowered DHEAS is characterized by small
      FEV1 and its insignificant rise in response to berotek therapy.

PMID- 19177791
TI  - [Production of certain cytokines in blood sera of patients with hypertensive
      disease and early stages of concomitant chronic obstructive pulmonary disease].
AB  - The results of investigation of blood serum interleikins in hypertensive patients
      in combination with early stages of chronic obstructive pulmonary disease (COPD)
      are presented. The increase of interleikin 1beta, tumor necrosis factor-alpha in
      hypertensive patients of the I - II stages in comparison with healthy person was
      marked. In the presence of accompanied COPD of the I stage more increased number
      of cytokins was determined. Changes of interleukin-4 patients of both groups were
      not found.

PMID- 19177792
TI  - [Quality of life in women with arterial hypertension in the climacteric period].
AB  - This study was designed to compare quality of life (QL) in women with arterial
      hypertension (AH) and with normal arterial pressure in the climacteric period. It
      included 146 postmenopausal women with AH (age median 57 years). The control
      group comprised 146 women without AH matched by age and duration of menopause. QL
      was assessed from the results of the SF-36 questionnaire and the severity of
      climacteric syndrome (CS) based on the modified menopausal index (MMI), pain in
      the back, joints, heart and headache, and also with the use of the visual analog
      scale (VAS). The severity of CS in patients with AH, headache, and cardialgia was
      much greater compared with controls. AH was associated with limitations as
      assessed by physical functioning (P = 0.004), physical role functioning (P =
      0.026), role-emotional functioning (P = 0.0001), and psychic health scales P =
      0.011). At the same time, AH was unrelated to substantial limitations as apparent
      from pain (P = 0.715) and social functioning (P = 0.052) scales. Estimates of
      general health status in women with AH were significantly lower than in its
      absence (P < 0.001). To summarize, AH considerably deteriorates QL in
      postmenopausal women.

PMID- 19177793
TI  - [Circadian rhythms of appealability and lethality in patients with exotoxicoses].
AB  - Retrospective analysis of 11,551 medical cards of patients who applied for urgent
      medical aid revealed circadian rhythms of appealability in different groups of
      them (suicides, accidental poisoning, etc.). Circadian rhythms were found to be
      related to the patients' age and sex. Also, a circadian rhythm of fatal outcomes
      in patients with acute exotoxicosis was distinguished.

PMID- 19177795
TI  - [Characteristic of inflammatory infiltrate of gastric mucosa in patients with
      grade II-III gastric dysplasia and of stomach cancer].
AB  - The study included 85 inpatients and outpatients in whom composition of
      inflammatory infiltrate from gastric mucosa (GM) was determined at the
      Oncological Research Institute, Tomsk Research Centre of the Siberian Division,
      Russian Academy of Medical Sciences. The patients were allocated to 4 groups
      depending on nosological form of the disease. Group 1 comprised 21 patients with
      grade II-III GM epithelial dysplasia, group 2 - 24 patients having stomach cancer
      (histologically confirmed adenocarcinoma), group 3 - 19 patients with stage II
      III mucinous gastric carcinoma, group 4 - 20 allegedly healthy subjects without
      signs of gastrointestinal pathology. It was shown that dysplastic processes in GM
      are associated with an increase of neutrophil, eosinophil, macrophage, and mast
      cell count along with a drop in the number of lymphocytes and plasmocytes. Stroma
      of invasive stomach cancer underwent intense inflammatory infiltration
      accompanied by a rise in the number of lymphocytes, plasmocytes, and neutrophils.
      Mucinous gastric carcinoma was characterized by an increase of the number of
      neutrophils and macrophages. Patients having adenocarcinoma of the stomach showed
      enhanced plasmocytic infiltration by plasmocytes with a low number of eosinophils
      and mast cells. It is concluded that characteristics of inflammatory GM
      infiltrate may be useful for the objective assessment of stomach cancer risk in
      patients with GM dysplasia, formation of a high oncological risk group, adequate
      dynamic monitoring and treatment of these patients.

PMID- 19177794
TI  - [Serologic screening for preneoplastic pathology and early stomach cancer].
AB  - Cancer of stomach is currently regarded as the final result of a staged
      multifactor process during which the microenvironment affects cells and causes
      their changes. One of the main triggering factors is Hp infection. Adenocarcinoma
      of stomach develops via stages of gastritis, precancerous changes, and cancer.
      The possibility to prevent cancer ensues from the potential irreversibility of
      premalignant processes in gastric mucosa, in the first place its atrophy; hence,
      the importance of its early diagnosis. The state of the endoscopic service in
      this country is inadequate for mass screening of patients with symptoms of
      dyspepsia. "GastroPanel", a new serological test for the diagnosis of gastric
      pathology provides information about histological and functional characteristics
      of gastric mucosa in the antral and fundal regions of the stomach. The method
      determines serum gastrin-17, pepsinogen-1, and IgG expressed in response to Hp
      infection. Our results demonstrate high diagnostic efficiency of "GastroPanel" as
      a screening technique for atrophic gastritis and assessment of stomach cancer
      risk.

PMID- 19177796
TI  - [Depressions in schizophrenic patients after the management of acute psychosis].
AB  - The study of depressions in 183 schizophrenic patients after the management of
      acute psychosis included evaluation of depressive symptoms, their relation to
      other psychopathologic syndromes, and the efficiency of drug therapy. The Calgary
      scale (CDSS) was used to assess severity of depression in schizophrenia along
      with other standardized psychometric scales to characterize general
      psychopathologic, positive, and negative symptoms, locomotor disturbances, other
      concomitant disorders, and general clinical picture. The predominance of
      depressive conditions with adynamic symptoms was documented. The majority of
      depressions occurred after the first attack. Those developing in the early post
      attack period differed from depressions within a few months after the reduction
      of psychosis. Syndromic nature of depressions was evident from the number of
      psychotic episodes experienced by the patients. Depressive symptoms that
      developed after the management of the acute psychotic state could be efficiently
      and safely relieved by additional differential treatment with antidepressants.
      Depressive symptoms in schizophrenia are not predictors of poor prognosis
      provided the patient receives adequate therapy. More attention is needed to
      identification and adequate treatment of depression in schizophrenia. Optimized
      therapy of affective disorders in schizophrenic patients permits to improve
      prognosis of the disease.

PMID- 19177797
TI  - [The use of hepatoprotector LiverPro in combined therapy of chronic viral
      hepatitis C].
AB  - We analysed clinical characteristics, laboratory findings, nature and frequency
      of side effects, and positive virologic response rate in 20 patients with chronic
      viral hepatitis C (HCV) given combined antiviral therapy with PEG-Intron,
      ribavirin, and LiverPro hepatoprotector (Santegra, USA, two capsules twice daily)
      during 3 months. The results were compared with those obtained in the control
      group of HCV patients receiving the same treatment excepting the hepatoprotector.
      Clinical manifestations of HCV in the former group disappeared 7-10 days earlier
      than in control. Also, cytolytic syndrome resolved in these patients, the
      positive virologic response rate was 20% higher and the frequency of severe side
      effects of interferon therapy that required its withdrawal was 10% lower. The
      authors recommend to include LiverPro in combined therapy of HCV.

PMID- 19177798
TI  - [Clinical approaches to the treatment of postnecrotic cysts of pancreatic head].
AB  - A total of 110 surgical interventions were undertaken to treat 98 patients with
      pseudocysts of the head of pancreas. Internal drainage was performed in 72
      patients including 43 laparatomies and 30 endoscopic procedures for the
      construction of cystodigestive anastomoses. Surgery with paracentesis drainage
      was practiced in 35 patients largely for the management of acute immature or
      suppurative cysts. Two patients underwent gastropancreatoduoudenal resection.
      Assessment of immediate and late outcomes of different methods of internal
      drainage demonstrated that endoscopic technique has an advantage over other
      modalities.

PMID- 19177800
TI  - [Elaboration of the general conception of disease in the works of V. Kh.
      Vasilenko].

PMID- 19177799
TI  - [Cartilage oligomeric matrix protein, a possible marker of synovitis in early
      knee joint osteoarthrosis].
AB  - Serum levels of cartilage oligomeric matrix protein (COMP) were measured in 88
      patients with early knee joint osteoarthrosis and 20 healthy donors. All the
      patients were examined clinically, by radiography and arthrosonography. COMP was
      measured with respect to the stage of knee joint osteoarthrosis and to the
      presence or absence of synovitis. It was lowest in patients showing no changes on
      X-ray images and free from synovitis. The COMP level increased as the pathogenic
      process progressed. In patients with synovitis, it was significantly higher than
      in the absence of joint inflammation. It is concluded that COMP level may be a
      useful marker of synovitis in early gonarthrosis.

PMID- 19177801
TI  - [Neuroethics in Japan--current view and future visions].
AB  - Neuroethics was originated in 2002 in the United States. In 2004, the Research
      Institute of Science and Technology for Society (RISTEX), a subsection of Japan
      Science and Technology Agency (JST), launched a neuroethics research group as the
      first research group to focus on the academic study and public engagement in
      neuroethics in Japan. In this article, the authors summarize the activities of
      RISTEX, JST during the brief history of neuroethics in Japan, and subsequently
      compare their current activities in neuroethics to those in other Western
      countries. We also introduce brief results of public survey of neuroscience
      research in Japan that suggest the significance of ethics and education regarding
      neuroscience to overview the future vision on neuroethics. We further discuss the
      role of neuroscientists in the future progress in neuroethics.

PMID- 19177802
TI  - [Neuroethics and bioethics--implications of Balkanization controversy].
AB  - There have been considerable disputes the positioning of neuroethics as a new
      field since its emergence in 2002. It is the novelty of the neuroethical issues
      and the necessity for updated moral approaches to them that leading exponents of
      neuroethics have emphasized; advances in neurosciences have created an entirely
      new field of moral inquiries that the conventional bioethics had never noticed.
      Futher, as neuroethics embraces the subdivision of ethics in neuroscience, it
      should take precedence over bioethics, which depends on the fundamental moral
      concepts without questioning their bases. Many bioethicists have squarely opposed
      these insistences and thereby detected the claim of neuroethics exceptionalism:
      the asserted newness of issues comes mainly from the ignorance of exponents of
      this new field regarding accumulated bioethical inquiries, so that the
      overlapping concerns between bioethics and neuroethics are passed on to the
      future by them. Moreover, bioethicists point out that the recent tendency of
      Balkanization in the field of bioethics could endanger the integrity of moral
      investigations. Subfields of bioethics, such as geneethics, neuroethics,
      nanoethics and so on, originate consecutively, entail wastage of valuable time
      and money, and increase the risk of fragmentizing moral considerations in an
      inconsistent way. By reviewing this controversy between neuroethics and
      bioethics, I argue that the relevant scientific investigations and technologies,
      which have appeared to promote the proliferation of bioethical sub-disciplines to
      date, are beginning to converge into 1 complex that demands not the division into
      subspecialities but the novel integration of bioethical inquiries: it is time to
      attempt the unification of bioethical applied ethics for moral considerations
      regarding nano-bio-info-cogno convergent technologies.

PMID- 19177803
TI  - [Social impact of recent advances in neuroscience].
AB  - Recent advances in neuroscience opened up new technical possibilities, such as
      enabling possible human mindreading, neuroenhancement, and application of brain
      machine-interface into everyday life, as well as the advent of new powerful
      psychotropic drugs. In addition to the conventional problems in bioethics, such
      as obtaining informed consent, neuroscience technology has generated new array of
      ethical questions. The social impact of advanced brain science or neuroscience
      and its technological applications is a major topic in bioethics, which is
      frequently termed as "Neuroethics." Here, we summarize the ethical, legal, and
      social issues of cutting-edge brain science by analyzing a classic science
      fiction novel entitled "Flowers for Algernon" authored by Daniel Keyes (1966).
      Three aspects of social problems faced by brain science are apparent: biomedical
      risk assessment, issues related to human subjectivity and identity, and socio
      cultural value of brain science technology. To understand this last aspect,
      enhancement-achievement and/or enhancement-treatment dichotomy can prove useful.
      In addition, we introduced the first national poll results in Japan (n=2,500) on
      the social impact of brain science. Although half the respondents believed that
      the advancement of brain science can aid individuals in the future, 56% of
      respondents suggested the necessity for guidelines or regulation policies
      mediating brain science. Technological application of brain science in treatment
      is generally accepted; however, not just for the personal purpose or enhancement
      of the normal function. In this regard, it is important to hold further
      discussions including the general public.

PMID- 19177804
TI  - [Deep brain stimulation and neuroethics].
AB  - The use of deep brain stimulation (DBS) for mental disorders has been discussed
      in Japan from the viewpoint of ethical problems. Trials of experimental therapies
      require a basis of sound scientific rationale. New standard therapy emerges from
      such trials through detailed analysis of the outcome and side effects. Long
      suffering patients with intractable symptoms may desperately seek an experimental
      therapy even though it has not yet been accepted as standard therapy. The ethical
      committee of each institution evaluates the level of scientific rationale and the
      expected level of benefits on the bias of the reported data, and decides whether
      the patients can receive the experimental therapy. However, the use of DBS for
      mental disorders is not based on sound scientific rational, since the disease
      mechanisms involved are far from understood. The data reported from the previous
      trials are insufficient for assuring the satisfactory results for mental disoder
      patients. Most institutions in Japan do not accept such levels of scientific
      rationale and expected benefits. Furthermore, from the cultural perspective,
      strong skepticism exists in Japan with regard to surgical interventions for
      mental disorders. Such an attitude is unexpectedly in harmony with many of the
      subjects currently discussed in the field of neuroethics. For example, who has
      the right to control DBS? How does someone decide the level of control of mental
      function by DBS? These questions are related to the discussion on how human
      society is formed and how the ethics are decided by considering both scientific
      rationale and human society.

PMID- 19177805
TI  - [Safety and neuroethical consideration of deep brain stimulation as a psychiatric
      treatment].
AB  - Deep brain stimulation (DBS) is a surgical treatment involving the implantation
      of a medical device, which sends electrical impulses to specific parts of the
      brain. DBS in select brain regions has provided remarkable therapeutic benefits
      for treatment-resistant movement and affective disorders such as Parkinson's
      disease. DBS directly alters brain activity in a controlled manner, and its
      effects are reversible. Lately, DBS treatment has been used for the treatment of
      various psychiatric disorders, such as obsessive compulsive disorder, Tourette
      syndrome, and severe depression. However, DBS therapies for affective disorders
      are still at their experimental stage, and some scientists point out that there
      may be a risk involved, because the device implanted in a person's brain may
      alter his/her brain function and hence his personal identity. With support from
      the New Energy and Industrial Technology Development Organization (NEDO),
      Japanese government, we conducted international research on the effects of DBS
      therapies for psychiatric disorders, examined the safety of such therapies, and
      clarified the conditions for proper application of the DBS technique. The
      research items were as follows: (1) safety issues concerning the deterioration of
      DBS electrodes and the possibilities of developing new and better materials, (2)
      the role of coordinators who mediate between patients and DBS devices, (3) social
      concerns regarding personality changes/brain plasticity, (4) re-examination of
      ethical debates on prefrontal lobotomy (lessons from the past), (5) possible use
      of DBS for the purpose of brain enhancement, and (6) end users' expectations and
      fears toward DBS.

PMID- 19177806
TI  - [Thrombolysis by intravenous tissue plasminogen activator (t-PA)--current status
      and future direction].
AB  - In Japan, the intravenous tissue plasminogen activator (t-PA) Alteplase (0.6
      mg/kg) administration of the within 3 h of the onset of acute ischemic stroke was
      approved for therapeutic use in the year 2006. t-PA induces thrombolysis in
      patients with acute ischemic stroke, and this method has gradually gained
      recognition among physicians and the general population. However, the number of
      patients who were treated using Alteplase is low (4,000-5,000 patients/year), and
      this figure accounts for only 2-3% of the annual number of cases of ischemic
      stroke. There is little doubt that Alteplase treatment is a potentially effective
      modality for some patients with acute ischemic stroke. The post-marketing
      surveillance of 4,749 Japanese patients treated using Alteplase showed that 33%
      of the patients had modified Rankin scale (mRS) scores of 0-1, 17% of patiens
      died and 4.5% presented with symptomatic intracerebral hemorrhage (ICH); these
      results were comparable to those from other countries. The expansion of the
      therapeutic time window has been a matter of concern. The investigators of the
      European Cooperative Acute Stroke Study (ECASS) have reported that there was
      significant improvement in the clinical outcomes of patients with acute ischemie
      stroke when Alteplase was administered 3-4.5 h after the onset of the symptoms.
      Mismatches in perfusion- and diffusion-weighted (DW) magnetic resonance imaging
      (MRI) images have been used for selecting patients 3 h after the onset of
      symptoms, and the findings from MRI, dwimages (DWI) and MR angiography are
      practical predictors of t-PA therapy within 3 h of onset. The Middle Cerebral
      Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan study showed
      that local intra-arterial fibrinolysis is effective in patients with embolic MCA
      occlusion within 6 h of the onset of symptoms. Combining the initiation of
      intravenous t-PA administration with further intra-arterial fibrinolysis or
      mechanical thrombolectomy may improve the recanalization rate. Thrombolysis in
      combination with ultrasound-enhanced clot lysis is another attractive therapy. In
      Japan the neuroprotective agent edaravone (radical scavenger) is commonly used in
      combination with t-PA, and it is expected to decrease the hemorrhagic
      transformation after t-PA administration. Acute cerebral ischemic symptoms may
      occasionally precede thoracic aortic dissection. Thoracic aortic dissection after
      t-PA administration may prove to be fatal, and it is an important disorder that
      must be differentially diagnosed.

PMID- 19177807
TI  - [Transcranial direct current stimulation--a new tool for human cognitive
      neuroscience].
AB  - Transcranial direct current stimulation (tDCS) is a non-invasive procedure of
      cortical stimulation, in which weak direct currents are used to polarize target
      brain regions. Depending on the polarity of the stimulation, tDCS can increase
      (anodal tDCS) or decrease (cathodal tDCS) cortical excitability in the stimulated
      brain regions and thereby enable the investigation of the causal relationships
      between brain activity and behavior. Recently, tDCS has been increasingly used to
      investigate human cognitive and motor functions in both healthy volunteers and
      neurological patients. Although tDCS generally produces diffuse cortical
      stimulation over a period of time, it has several advantages over other brain
      stimulation tools such as transcranial magnetic stimulation (TMS). First, since
      tDCS produces less artifacts such as acoustic noise and muscle twitching, it is
      more suitable for double-blind, sham-controlled studies and clinical
      applications. Second, tDCS is not very expensive and can be performed with
      compact equipment, it can be easily combined with ongoing projects in
      neuroscience and psychology laboratories. Third, the facilitation of motor and
      cognitive functions by anodal tDCS may have great potential for cognitive and
      motor enhancement, for example, to support learning in healthy volunteers and to
      expedite the rehabilitation process in neurological patients. Finally, thus far,
      seizure incidents have not been reported in tDCS studies, tDCS has thus become a
      complementary tool to TMS and occupies a unique position in current cognitive
      neuroscience.

PMID- 19177808
TI  - [Inter-rater reliability while using the Toronto Western Spasmodic Torticollis
      Rating Scale (TWSTRS) in patients with cervical dystonia].
AB  - We examined the inter-rater reliability for the evaluation of patients with
      cervical dystonia by using the Toronto Western Spasmodic Torticollis Rating Scale
      (TWSTRS) (translated into Japanese). The TWSTRS is a rating scale that assesses
      patients with cervical dystonia by grading their symptoms on a subscale of
      severity, disability, and pain. This study used to TWSTRS-severity scores to
      examine the inter-rater reliability among 27 evaluators (neurologists) by using
      videotaped images of 2 patients. Along with the total-severity score on the
      TWSTRS, the intra-class correlation (ICC) and the lower limit of the 95%
      confidence interval were calculated as indices of inter-rater reliability. A high
      ICC of 0.745 was obtained. The ICC obtained from another study conducted outside
      Japan was 0.763, which is almost equivalent to the result of our study. Thus, the
      TWSTRS has a favorable inter-rater reliability which suggests that this scale was
      sufficiently reliable to be used as an accurate and easily available rating tool
      during the treatment of cervical dystonia.

PMID- 19177809
TI  - [Body lateropulsion as the main symptom of pontine vascular disease--comparison
      with lateral medullary vascular disease].
AB  - Lateropulsion of the body is rarely encountered as an isolated or predominant
      manifestation of pontine cerebrovascular disease. We compared 2 cases of pontine
      vascular lesions with 3 cases of lateral medullary infarction; all the patients
      had presented with body lateropulsion. The patients with pontine lesions tended
      to full on the side contralateral to the lesion,whereas the patients with lateral
      medullary infarction, fell on the ipsilateral side. Lateropulsion itself improved
      within 1 or 2 weeks in all the patients. The pontine lesion was localized to the
      paramedian tegmentum, just ventral to the fourth ventricle, while the medullary
      infarction was localized to the lateral surface of the medulla oblongata. The
      present findings support the possibility that body lateropulsion in patients with
      pontine vascular lesion is attributed to lesions in the graviceptive pathway that
      ascends through the paramedian pontine tegmentum.

PMID- 19177810
TI  - [Case of juvenile myoclonic epilepsy misdiagnosed as simple partial seizure for
      more than 60 years].
AB  - A 77-years-old woman was admitted to our hospital due to uncontrolled myoclonus
      and generalized seizure. Since the age of 17, she has been suffering from
      myoclonic jerks and partial convulsions in her right arm. Administration of
      several unknown anticonvulsants had not alleviated her condition. She was able to
      spend her life without a handicap, except for the symptoms described above. She
      has been experiencing psychological stress since the age of 50, which has
      resulted in worsening of her symptoms, and she was prescribed phenytoin,
      carbamazepine, and phenobarbital, which were also ineffective. When a generalized
      convulsive attack occurs, she shows rapid muscle twitches in her right arm and
      her consciousness is clear. She also has cerebellar ataxia in her extremities.
      Brain magnetic resonance imaging (MRI) showed obvious cerebellar atrophy, and an
      electroencephalogram revealed a diffuse spike and wave complexes. A surface
      electromyogram (EMG) confirmed myoclonus in both arms. We diagnosed her as having
      juvenile myoclonus epilepsy and initiated sodium valproate monotherapy, which
      relieved the symptoms. The observed cerebellar ataxia might be due to long-term
      administration of phenytoin. When a neurologist encounters an intractable seizure
      without loss of consciousness, surface EMG is useful for diagnosing this
      treatable disease.

PMID- 19177811
TI  - [Case of internal carotid artery stenosis complicated with shower embolism during
      filter-protected carotid artery stenting].
AB  - Recently, carotid artery stenting (CAS) has gained a lot of interest as a
      potentially valuable minimally invasive alternative to carotid endarterectomy.
      Since the occurrence of distal embolization as a result of CAS is still a major
      concern, an embolus protection device is usually employed during the procedure.
      Here, we report a case of internal carotid artery (ICA) stenosis complicated with
      shower embolism during CAS with an embolus protection filter. A 77-year-old man
      who had a history of coronary bypass surgery was referred to our department for
      the treatment of carotid artery stenosis. Angiography showed high-grade stenosis
      at the origin of the right ICA. Plaque magnetic resonance imaging (MRI) showed a
      hyperintense lesion at the right ICA stenosis, indicating the presence of a lipid
      rich plaque. Since cerebral circulation was impaired significantly in the right
      cerebral hemisphere, CAS was performed for the right ICA stenosis, with an
      embolus protection filter. A self-expandable stent was placed in the right ICA
      following predilation. During stenting, plaque protrusion was identified and
      treated with balloon angioplasty. The patient developed right hemiparesis
      postoperatively. MRI showed multiple infarction in the right cerebral hemisphere.
      The symptom resoeved 7 days later. A potential disadvantage of the filter device
      is incomplete protection from emboli or failure to protect against soluble
      mediators. An embolus protection filter is not suitable for capturing the debris
      from lipid-rich plaques.

PMID- 19177812
TI  - [Case of hydrocephalus after cervical laminoplasty for cervical ossification of
      the posterior longitudinal ligament].
AB  - We report a rare complication of cervical laminoplasty in cervical ossification
      of the posterior longitudinal ligament (OPLL). A 69-year-old man suffered from
      gait disturbance and numbness of the bilateral hand for 6 months. He underwent C3
      7 partial laminoplasty at the department of orthopedic surgery. After the
      operation, his symptoms immeadiately disappeared. However 1 month later, he
      presented with memory disturbance and gait disturbance. A computed tomography
      (CT) scan of head showed hydrocephalus, and cervical magnetic resonance imaging
      (MRI) showed fluid collection in the epidural and subcutaneous spaces. A
      ventriculoperitoneal shunt was performed, and it resolved the memory and gait
      disturbance. This is the second case report of hydrocephalus after laminoplasty
      for cervical OPLL.

PMID- 19177813
TI  - [One hundred books which built up neurology (25)- William Cullen "First lines of
      the practice of physic" (1776-1790)].

PMID- 19177814
TI  - Acute cardiac tamponade: anticipate the complication.
AB  - Acute cardiac tamponade (ACT) is a serious complication following cardiac
      surgery. ACT occurs as a result of post-operative bleeding in the first five to
      seven days following the operative procedure. Although the incidence of ACT is
      relatively low, the consequences include cardiac compromise and even death. This
      article includes a review of the pathophysiology, assessment, prevention, signs,
      diagnosis, and management strategies for patients who develop ACT The knowledge
      gleaned from this article will enable the critical care nurse to anticipate and
      prevent this life-threatening complication and, thus, optimize outcomes for this
      complex surgical population.

PMID- 19177815
TI  - Glycemic control in diabetic and non-diabetic cardiac surgical patients and
      length of hospital stay.
AB  - BACKGROUND: Maintaining blood glucose levels (BGL) within normoglycemic range has
      been shown to reduce morbidity and mortality in critically ill patients. However,
      there is little evidence that maintenance of normoglycemic BGL is beneficial for
      diabetic and non-diabetic patients who undergo cardiac surgery. PURPOSE: To
      examine the relationship between BGL and length of stay (LOS) of cardiac surgical
      patients. METHODS: Data were obtained from the Safer Healthcare Now Project
      database in the cardiovascular intensive care unit (CVICU) at the Foothills
      Medical Centre, Calgary, Alberta, and included two BGL from cardiac surgery
      patients: BGL 1 was collected within four hours preoperatively, BGL 2 was
      collected postoperatively 24 hours after BGL 1. CVICU LOS and total hospital LOS
      were obtained from the Tracer database of the Department of Critical Care
      Medicine, Calgary Health Region. Demographic, clinical, and surgical data were
      collected from health records. RESULTS: For the 398 patients, no relationship was
      found between pre- and postoperative BGL and LOS. Although pre- and postoperative
      BGL were not different between diabetics and non-diabetics, diabetics had longer
      CVICU LOS and total hospital LOS. Age, preoperative HgbA1C, type of surgery,
      cross-clamp and cardiopulmonary bypass times, APACHE II scores, and postoperative
      complications also affected LOS. CONCLUSION: In this cohort of cardiac surgical
      patients, pre- and postoperative BGL did not affect LOS.

PMID- 19177816
TI  - Implementation of a nurse-driven sedation protocol in the ICU.
AB  - BACKGROUND: Managing anxiety, pain and delirium in critically ill patients is an
      ongoing challenge. Differences in physician practice, variations of
      pharmacological agents, as well as concentrations and units can increase the risk
      of medication error Personal preferences, subjectivity, and nurses' level of
      expertise are variables when titrating analgesic and sedation infusions. PURPOSE:
      The purpdse of this study was to evaluate the perceived benefits of implementing
      a standardized nurse-driven sedation protocol in the ICU. We examined its impact
      on the rates of medication errors and perceptions of staff using the protocol.
      DESIGN: This descriptive study used a survey to collect data. SAMPLE: We used a
      convenience sample of 75 nurses who worked in the ICU during the implementation
      of the sedation protocol. RESULTS: Analysis of variance was completed comparing
      all sub-scale scores. No statistical significance was found, but scores did not
      decrease over time. No medication errors or near misses were reported throughout
      the sedation protocol implementation. Qualitative comments from staff provided
      feedback and assisted in identifying issues with the protocol. CONCLUSION: We
      believe that the implementation of the sedation protocol has been beneficial in
      our adult ICU. Findings indicate that with experience and resources nurses can
      manage anxiety, pain and delirium more confidently than without such a protocol.
      Critical care nurses, given the right tools, education, and support can make
      decisions that promote positive outcomes for patients receiving sedation and
      analgesia in the ICU.

PMID- 19177818
TI  - [Subjective Visual Vertical test: normative values in healthy population].
AB  - INTRODUCTION: Subjective Visual Vertical test (SW test) can be applied to measure
      one of the functions of the vestibular apparatus, its afferent pathways and
      nuclei within the brain stem. The test is based on the subjective assessment of
      verticality. The possibility of perceived visual vertical in healthy subjects can
      show deviation with accuracy of -/+ 2 degrees at most. OBJECTIVE: The goal of the
      study is to present the results of the SVV test developed at our department.
      METHOD: Two kinds of testing procedures were applied; the static test during
      which the subjects evaluated the verticality on a static background; the dynamic
      test during which the subjects evaluated the verticality after 20 seconds of
      rotation of the background to the right or to the left. Ninety-five healthy
      subjects aged between 21 and 79 years were tested. The whole group was divided
      into smaller groups according to age criterium. RESULTS: The results showed
      statistically significant bigger SVV tilt in the subjects aged over 45 years than
      in the younger subjects. The arithmetic mean of the tilt to the left or tilt to
      the right in the group younger than 45 years was 0.42 degrees during the static
      test and 0.49 degrees during the dynamic test. The arithmetic mean for the group
      older than 45 years was 0.67 during the static test and 0.68 during the dynamic
      test. CONCLUSION: The testing indicated that SVV perception showed a bigger tilt
      according to age. This should be taken into consideration in individual testing
      and evaluation of functional ability.

PMID- 19177819
TI  - [Comparative analysis of conventional and eversion carotid endarterectomy-
      prospective randomized study].
AB  - INTRODUCTION: Studies completed in the last decade of the 20th century showed
      benefits of carotid endarterectomy in the prevention of stroke in patients with a
      high-grade stenosis of the internal carotid artery. OBJECTIVE: The aim of this
      prospective, randomized study was the comparison of early and long-term results
      between the conventional and eversion carotid endarterectomy, and literature
      review. METHOD: By the method of random choice, 103 patients were operated on
      using the eversion carotid endarterectomy and 98 patients using the conventional
      technique. Operative treatment was carried out under general anaesthesia.
      Following the clammping of the carotid artery, retrograde blood pressure was
      determined by a direct puncture of the internal carotid artery above the stenotic
      lesions. In patients with retrograde pressure below 20 mm Hg intraluminal
      shunting was routinely performed. Early results were estimated (during the first
      seven postoperative days) based on mortality, central neurological complications
      (stroke, TIA) and cranial or cervical nerve lesions. Long-term results were
      estimated (after at least two years) based on long-term survival rate, central
      neurological complications (stroke,TIA) and the incidence of haemodynamically
      significant restenosis of the carotid artery treated by endarterectomy. RESULTS:
      The average time of clamming of the internal carotid artery in the eversion
      carotid anderectomy group was 5.36 minutes shorter than in the group treated by
      the conventional technique. Student's t-test showed a statistically highly
      significant difference in the time needed for clamming of the internal carotid
      artery between the two groups. The average duration of eversion endarterectomy
      (82 minutes) was most often 19 minutes shorter than the duration of the
      conventional endarterectomy (101 minutes). Student's t-test showed a
      statistically highly significant difference in the average length of surgeries.
      The distal intimal fixation was more often needed during the conventional carotid
      endarterectomy (34.7%) compared to eversion endarterectomy (3.9%). Chi 2-test
      showed a statistically highly significant difference. CONCLUSION: Eversion
      carotid endarectomy represents a statistically significantly shorter procedure.
      Distal intimal fixation demanded by this procedure is very rare, clammping of the
      internal carotid artery is significantly shorter, and it also has a lower rate of
      the early neurological complications. Based on the results of this study, as well
      as the opinions of other authors, it can be concluded that the eversion carotid
      endarterectomy has an advantage over the conventional procedure.We recommend
      conventional procedure only in cases when retrograde pressure indicates the use
      of the intraluminal shunting.

PMID- 19177820
TI  - [Mortality from heart attack in Belgrade population during the period 1990-2004].
AB  - INTRODUCTION: In most countries, cardiovascular diseases are the leading
      disorders, with ischemic heart diseases being the leading cause of death.
      According to WHO data, every year about 17 million people die of cardiovascular
      diseases, which is 30% of all deaths. Ischemic heart diseases contribute from one
      third to one-half of all deaths due to cardiovascular diseases. Three point eight
      million men and 3.4 million women in the world die every year from ischemic heart
      diseases, and in Europe about 2 million. The highest mortality rate from ischemic
      heart diseases occurs in India, China and Russia. OBJECTIVE: The aim of this
      descriptive epidemiological study was to determine heart attack mortality in
      Belgrade population during the period 1990-2004. METHOD: In the study, we
      conducted investigation of Belgrade population during the period 1990-2004.
      Mortality data were obtained from the city institution for statistics. The
      mortality rates were calculated based on the total Belgrade population obtained
      from the mean values for the last two register years (1991 and 2002). The
      mortality rates were standardized using the direct method of standardization
      according to the world (Segi) standard population. RESULTS: In the Belgrade
      population during the period 1990-2004, the participation of mortality rate due
      to heart attack among deaths from cardiovascular diseases was 17% in males and
      10% in females. In Belgrade male population, mean standardized mortality rates
      (per 100,000 habitants) were 50.5 for heart attack, 8.3 for chronic ischemic
      heart diseases and 4.6 for angina pectoris, while in females the rates were 30.8,
      6.7 and 4.2, respectively. Mortality from ischemic heart diseases and from heart
      attack was higher in males than in females. During the studied 15-year period, on
      average 755 males and 483 females died due to heart attack every year. Mean
      standardized mortality rates per 100,000 habitants were 50.0 in male and 31.1 in
      female population. Males died 1.6 times more frequently from heart attack than
      females. During the studied period, mean standardized mortality rates from heart
      attack, in the population aged over 30 increased with age both in male and female
      population. However, males tended to die from heart attack at an earlier age than
      females, with death rates for males approximately the same as those for women who
      were 10 years older. CONCLUSION: In Belgrade during the period from 1990-2004, we
      found that there was an increasing trend in mortality rate due to cardiovascular
      diseases, while the trend of mortality rate from heart attack was constant with
      insignificant oscillations.

PMID- 19177821
TI  - [Clinical characteristics and survival of children with hepatoblastoma--single
      centre experience].
AB  - INTRODUCTION: Hepatoblastoma is the most frequent malignant liver tumour of
      childhood and it accounts for 1% of all paediatric cancers. The outcome is
      significantly improved by introducing intensive chemotherapy regimens followed by
      complete surgical tumour resection. The long-term survival is 75-95% at present.
      OBJECTIVE: To summarize clinical characteristics and treatment results in
      children with hepatoblastoma. METHOD: The patients diagnosed with hepatoblastoma
      and treated at the Department of Haematology of the University Children's
      Hospital in Belgrade, between January 1995 and December 2007 were retrospectively
      analysed. We analysed mode of therapy, surgical management and patients' survival
      according to Kaplan Mayer statistical test. RESULTS: Eleven patients were treated
      (ten boys and one girl), aged from 6 months to 13 years, mean 32 months, median
      12 months. The most frequent presenting sign was abdominal distension. Routine
      laboratory examination showed elevated alpha-fetoprotein (AFP), range 147 to
      44880 ng/ml, mean 8667 ng/ml.Ten patients (91%) had elevated platelet count,
      range 450 to 909 x 10(9)/l. Initial lung metastasis developed in 3 patients
      (27%).The diagnosis was established by an open surgical biopsy in 6 patients and
      after complete tumour resection in 4 patients, namely 2 patients after
      preoperative chemotherapy and in 2 patients with no previous chemotherapy.
      Histopathology verified hepatoblastoma in 10 patients: in 7 patients with
      epithelial type and in 3 patients with mixed epithelial-mesenchyme type. Six
      patients were in continuous remission with mean follow up of 58 months. One
      patient was lost to follow up. Four patients died; three patients due to disease
      progression and one patient due to sepsis after the first cycle of chemotherapy.
      CONCLUSION: Combined preoperative chemotherapy with complete tumour resection
      followed by postoperative chemotherapy results in a high percentage of definitive
      cures.

PMID- 19177822
TI  - [Importance of genotyping of thiopurine S-methyltransferase in children with
      acute lymphoblastic leukaemia during maintenance therapy].
AB  - INTRODUCTION: Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyses
      the inactivation of mercaptopurine (MP) which is widely used in the treatment of
      acute lymphoblastic leukaemia (ALL) of childhood. Potentially fatal myelotoxicity
      may develop after standard doses of MP in TPMT deficient patients. OBJECTIVES: To
      establish if individually tailored doses of MP can reduce myelotoxicity in ALL
      patients carrying mutations in the TPMT gene.To establish if variable number of
      tandem repeats (VNTR) genotype influences the treatment effects of MP. METHOD:
      Fifty randomly selected patients treated according to ALL IC-BFM 2002 protocol
      were tested for most frequent TPMT gene mutations using PCR based methods. VNTR
      genotype was determined in 20 children by PCR methods. During the maintenance
      phase, we recorded the number of weeks when therapy was applied in either full
      doses, reduced doses or when patients were without any therapy. RESULTS: Fifty
      children were examined, 29 boys (58%) and 21 girls (42%); age ranged from 1.8
      17.3 years (median 6.2 years). Four patients (8%) were heterozygous for TPMT
      mutations, all of them carrying the TPMT*3A variant. After 12, 14, 16 and 19
      weeks of therapy with reduced doses of MP, the patients switched to full doses
      due to good tolerance.There was no therapy omission. Cumulative dose of MP was
      reduced for 7.8%, 7.4%, 11.2% and 16.6%, respectively, in patients with TPMT
      mutations. No significant difference was found between children with no mutations
      and TPMT heterozygotes regarding full dose therapy (53.6 vs. 55.7 weeks,
      respectively) and reduced dose therapy (19.9 vs. 15.2 weeks respectively). The
      number of detected VNTRs ranged from four to seven. The majority of patients had
      different number of VNTRs on homologous chromosomes. Most frequently detected
      polymorphism was VNTR*5. No correlation was found between TPMT and VNTR genotype
      inheritance. CONCLUSION: Obeying pharmacogenetic principles in the treatment of
      childhood ALL may improve the tolerance of therapy with MP.

PMID- 19177824
TI  - [The prevalence of childhood obesity in a sample of schoolchildren in Belgrade].
AB  - INTRODUCTION: Obesity in children has become a global epidemic with many health
      and social consequences that often continue into adulthood. According to the
      International Obesity Task Force report from 2005, Serbia has had one of the most
      rapidly increasing trends in the prevalence of childhood obesity during the last
      10 years. OBJECTIVE: The aim of the study was to estimate the prevalence of
      childhood obesity in a sample of schoolchildren in Belgrade and to investigate
      the correlation between child obesity and the presence of selected diseases.
      METHOD: The study comprised of 854 pupils from two primary schools in Belgrade.
      The anthropometric data, as well as the data on the presence of selected diseases
      were obtained from medical records of regular health check-ups in the period from
      2006-2007. The classification of childhood obesity was done according to the WHO
      percentiles reference data for obesity and overweight in children. Statistical
      analyses included chi 2 test and correlation analysis. RESULTS: In our sample of
      schoolchildren, the prevalence of obesity was 30.7%. The following diseases were
      present among the pupils: spinal deformities 192 (22.5%), chest wall deformities
      90 (10.5%) and foot deformities 226 (26.5%). Statistically significant
      correlation was registered between child obesity and the presence of spinal
      (p=0.192; p=0.001) and foot deformities (p=0.099; p=0.049). Chest wall
      deformities were more frequent in the group of children with normal weight
      compared with the obese group (chi 2=0.206; p=0.052). Statistically significant
      correlation was registered between childhood obesity and the presence of
      hypertension (p=0.261; p=0.001). Regular physical activity was in correlation
      with the absence of childhood obesity (p=-0.093; p=0.055). CONCLUSIONS: In our
      sample of Belgrade schoolchildren, we detected a high prevalence of obesity.
      Furthermore, a significant correlation between childhood obesity and the presence
      of hypertension, spinal deformities and foot deformities were also observed.

PMID- 19177823
TI  - [Positional installation of contrast cystography: a new approach in the diagnosis
      of vesicoureteral reflux].
AB  - INTRODUCTION: Positional installation of contrast cystography (PIC cystography)
      represents a new method to identify vesicoureteral reflux (VUR) that is
      unrevealed by standard diagnostic procedures. It is performed by radiological
      examination of the vesicoureteral junction during cystoscopic installation of the
      contrast medium at the ureteral orifice. OBJECTIVE: We studied the significance
      of PIC cystography to demonstrate VUR that failed to be revealed by standard
      voiding cystourethrography (MCUG), as well as the degree of the correlation of
      such a finding with endoscopic appearance and the position of the ureteral
      orifice (UO). METHOD: The aim of the paper was to analyze a sample of 5 children
      (4 girls and 1 boy), aged 6-15 years (mean 9.8 years) with recurrent febrile
      urotract infections, complicated with scarring changes of the renal parenchyma
      and normal findings on MCUG. The grade of VUR demonstrated by PIC cystography was
      classified using the standard hydrodistensional scale. RESULTS: All 5 patients
      had VUR, disclosed by PIC cystography, of whom in 4 it was unilateral and in one
      bilateral. Of 5 patients, 4 had VUR grade I and one grade II. All the children
      with VUR detected by PIC cystography also had evident cystoscopic abnormalities
      in the position and/or configuration of the ureteral orifice at the same side,
      while at the side with normal finding on PIC cystography, the endoscopic finding
      was also within normal limits. CONCLUSION: PIC cystography is the method of
      choice in the confirmation of VUR as the cause of recurrent urotract infection
      and its complications in children with a normal finding on standard MCUG. In all
      our patients with VUR verified by PIC cystography, at the same side we also
      revealed endoscopic changes in the position and/or configuration of UO.

PMID- 19177825
TI  - [Economic aspects of hospitaly treated pneumococcal pneumonia and the results of
      Pneumo 23 vaccine use in Serbia].
AB  - INTRODUCTION: In Serbia, there is a significant number of persons suffering of
      pneumococcal pneumonia. Persons aged 65 years or older, immunocompromised
      patients, patients with co-morbidities, such as chronic obstructive lung disease
      and congestive heart failure, are at the highest risk for developing pneumococcal
      pneumonia. Most of the patients are treated empirically, although it is often
      overlooked that Streptococcus pneumoniae can be resistant to the used
      antibiotics. The treatment costs of such inpatients and outpatients are very
      high. In Serbia, immunization of persons at risk to develop the diseases caused
      by Streptococcus pneumoniae is carried out using pneumococcus polysaccharide
      vaccine according to clinical indications. The exact number of immunized persons
      and the total number of registered patients are still unknown, but it is certain
      of being unjustifiably low. OBJECTIVE: The goal of the study was to investigate,
      during a one-year period, the number and basic characteristics of persons
      hospitably treated for pneumonia, the type of cause of the infection, applied
      antibiotic medications, duration and costs of hospital treatment at the Institute
      for Lung Diseases and Tuberculosis of the Clinical Centre of Serbia in Belgrade.
      METHOD: We retrospectively analyzed the medical records of patients with
      pneumonia treated at the Institute for Lung Diseases and Tuberculosis of the
      Clinical Centre of Serbia in Belgrade during 2006. RESULTS: During the observed
      one-year period, 290 patients underwent hospital treatment, of whom the cause of
      the infection was confirmed in 116 (40%). The average duration of hospitalization
      was 12 days, with treatment cost of 32,031.74 RSD (402.42 EUR) per patient. The
      treatment cost per patient including general and intensive care was 18,290.01 RSD
      (229.78 EUR). The distribution cost of Pneumo 23 vaccine in Serbia, without
      purchase tax, was 746.90 RSD (9.38 EUR). CONCLUSION: Pneumococcal pneumonia is a
      significant medical and economic problem for the healthcare system of Serbia. The
      use of antipneumococcal vaccination can be useful in decreasing the overall
      treatment costs related to pneumococcal infection.

PMID- 19177826
TI  - [Family characteristics of stuttering children].
AB  - INTRODUCTION: Stuttering is a functional impairment of speech, which is
      manifested by conscious, but nonintentionally interrupted, disharmonic and
      disrhythmic fluctuation of sound varying in frequency and intensity. Aetiology of
      this disorder has been conceived within the frame of theoretical models, which
      tend to connect genetic and epigenetic factors. OBJECTIVE: The goal of the paper
      was to study the characteristics of the family functioning of stuttering children
      in comparison to the family functioning of children without speech disorder,
      which confirmed the justification of the introduction of family orientated
      therapeutic interventions into the therapy spectrum of child stuttering. METHOD:
      Seventy-nine nucleus families of 3 to 6-year-old children were examined; of
      these, 39 families had stuttering children and 40 had children without speech
      disorder. The assessment of family characteristics was made using the Family
      Health Scale, an observer-rating scale which according to semistructured
      interview and operational criteria, measures 6 basic dimensions of family
      functioning: Emotional State, Communication, Borders, Alliances, Adaptability &
      Stability, Family Skills. A total score calculated from the basic dimensions, is
      considered as a global index of family health. RESULTS: Families with stuttering
      children compared to families with children without speech disorder showed
      significantly lower scores in all the basic dimension of family functioning, as
      well as in the total score on the Family Health Scale. CONCLUSION: Our research
      results have shown that stuttering children in comparison with children without
      speech disorder live in families with unfavourable emotional atmosphere, impaired
      communication and worse control over situational and developmental difficulties,
      which affect children's development and well-being. In the light of previous
      research, the application of family therapy modified according to the child's
      needs is now considered indispensable in the therapeutic approach to stuttering
      children. The assessment of family characteristics with special reference to the
      ability of parents to recognize specific needs of children with speech disorder
      and adequate interaction, as well as readiness of parents for therapeutic
      collaboration are the necessary elements in legal custody evaluations.

PMID- 19177827
TI  - [Parricide: psychiatric morbidity].
AB  - INTRODUCTION: Parricide is defined as a murder of parents by their children; the
      patricide is murder of father, while matricide is murder of mother. This entity
      is classified as homicide, but it differs in the fact that victims are parents
      and the killers are their children. Mostly, it is associated with psychiatric
      morbidity. OBJECTIVE: To describe sociodemographic and psychopathological
      characteristics of parricide committers and to analyze circumstances of parricide
      and psychiatric morbidity in order to achieve better recognition and prevention
      of risks. METHOD: This retrospective study included all homicide autopsy records
      (1991-2005) performed at the Institute of Forensic Medicine, Medical School,
      University of Belgrade. For further analyses, all parricide records were selected
      out. The study analyzed all available parameters, which concerned parricide
      committers, victims and the act itself. Methods of descriptive statistics were
      used. RESULTS: Between 1991 and 2005, there were 948 cases of homicide; of these,
      3.5% were parricides. The committers of parricide were on average 31.2 +/- 11.9
      years-old, 87.8% were males, 60.6% with psychiatric symptoms most commonly with
      schizophrenia, alcohol dependence, personality disorder etc. Victims were on
      average 63.7 +/- 11.9-years-old, 54.5% males, and 21.2% had a diagnosed mental
      illness. CONCLUSION: Parricide is a rare kind of homicide accounting for 3% of
      all homicides. Committers are mostly unemployed males in early adulthood who have
      mental disorder. The phenomenon of parricide deserves a detailed analysis of the
      committer (individual bio-psycho-social profile) and the environmental factors
      (family, closely related circumstances) to enable a precise prediction of the act
      and prevention of the fatal outcome, which logically imposes the need of further
      studies.

PMID- 19177828
TI  - [Possible values of UV index in Serbia].
AB  - INTRODUCTION: UV Index is an indicator of human exposure to solar ultraviolet
      (UV) rays. The numerical values of the UV Index range from 1-11 and above. There
      are three levels of protection against UV radiation; low values of the UV Index-
      protection is not required, medium values of the UV Index--protection is
      recommended and high values of the UV Index--protection is obligatory. The value
      of the UV Index primarily depends on the elevation of the sun and total ozone
      column. OBJECTIVE: The aim of the study is to determine the intervals of possible
      maximal annual values of the UV Index in Serbia in order to determine the
      necessary level of protection in a simple manner. METHOD: For maximal and minimal
      expected values of total column ozone and for maximal elevation of the sun, the
      value of the UV Index was determined for each month in the Northern and Southern
      parts of Serbia. These values were compared with the forecast of the UV Index.
      RESULTS: Maximal clear sky values of the UV Index in Serbia for altitudes up to
      500 m in May, June, July and August can be 9 or even 10, and not less than 5 or
      6. During November, December, January and February the UV Index can be 4 at most.
      During March, April, September and October the expected values of the UV Index
      are maximally 7 and not less than 3. The forecast of the UV Index is within these
      limits in 98% of comparisons. CONCLUSION: The described method of determination
      of possible UV Index values showed a high agreement with forecasts. The obtained
      results can be used for general recommendations in the protection against UV
      radiation.

PMID- 19177829
TI  - Orthopedic and trauma services in the healthcare system of Serbia.
AB  - Our aim has been to present the functioning of orthopaedic and trauma services in
      the healthcare system of Serbia. In the introduction, we present geographic,
      demographic, political and economic elements, which define more closely the
      position of Serbia in the Southeastern Europe. Further, the healthcare system of
      Serbia, organized in four levels, is presented: self-care, primary healthcare,
      secondary healthcare and tertiary healthcare, as well as the schedule of 20,157
      physicians engaged in healthcare. In addition, we point out numerous problems,
      which the system is faced with. Special attention is paid to orthopaedic and
      trauma services active within the system, its development, current condition and
      personnel education. We have concluded that, despite this being a middle-income
      country, the healthcare system is well developed. With 524 orthopaedic surgeons,
      working in 56 specialized departments, musculoskeletal diseases and trauma
      management are covered at all three healthcare levels. Nevertheless, the authors
      also underline weaknesses that are mostly of technical nature. Measures for their
      elimination and improvement of the entire service are also suggested.

PMID- 19177830
TI  - [Stylocarotid syndrome: a case report].
AB  - INTRODUCTION: The American otolaryngologist Eagle was the first to describe
      styloid syndrome in 1937 and the syndrome was named after him (Eagle's syndrome).
      The original description of two separate syndromes is connected with his name:
      classical syndrome, which almost constantly occurs after tonsillectomy and
      carotid artery syndrome, which occurs without tonsillectomy and also in cases
      when stylohyoid complex compresses the carotid segments and perivascular
      sympathetic fibers. In the following years, two more syndromes were defined:
      stylohyoid and pseudostylohyoid, which according to their manifestations,
      correspond to the genuine classical form. CASE OUTLINE: A 40-year-old male is
      presented, with a history of 3-year duration of pains in the upper part of the
      left side of the neck, in the left eye and its surroundings. Pain occurrences
      were not regular. Throbbing pains were most often provoked by sudden head
      movements and neck compression. He was healthy until the onset of these problems.
      The findings of all examinations were normal. The applied prophylactic therapy,
      typical for cluster headache, was without any effect. On 64-MSCT (multislice
      computed tomography), the neck arteries did not show any intraluminal pathology.
      The styloid processes were of normal length. On the left side, the styloid
      process tip pressed the internal carotid artery disturbing its longitudinal axis.
      CONCLUSION: In our presentation, the defined lengths of the styloid processes
      were normal. The medial angulation of the left styloid process was more expressed
      reaching 63.5 degrees (the right side angulation was normal). Persistent and
      throbbing pain in the region of the left eye with backward projection suggested
      compression on the internal carotid artery. Pains were most frequently provoked
      by head turning and neck compression. 64-MSCT diagnostics enabled us to determine
      the characteristics of styloid processes and their relation to the internal
      carotid artery. Improvement was achieved by administration of antiepileptic
      (gabapentin) and antidepressant (amitriptyline) drugs.

PMID- 19177831
TI  - [Persistent sciatic artery: a case report].
AB  - INTRODUCTION: The sciatic artery represents the earliest embryological blood
      supplyto the lower extremity. It regresses after the 3rd month of embryologic
      development. The proximal part of the sciatic artery eventually persists as the
      inferior gluteal artery. Rarely, however, it persists into adulthood when it is
      frequently associated with numerous possible complications (aneurysm formation,
      embolism, nerve compression, rupture, thrombosis). CASE OUTLINE: In March 1996, a
      48-year-old male was admitted for angiography of the blood vessels of the right
      inferior extremity, before an elective orthopaedic procedure. Arteriography of
      the right leg was done in a usual manner through the right common femoral artery
      in order to get an angiogram of the popliteal trifurcation and crural arteries.
      However, on the first field we noticed a hypoplastic superficial femoral artery,
      as well as a huge persistent sciatic artery (PSA) originating from the internal
      iliac artery running distally and overlapping the deep femoral artery. There were
      no aneurysm and stenotic changes of PSA. CONCLUSION: If clinical condition is
      stable, follow-ups at 12 months intervals should be done by means of ultrasound.
      The therapeutic decisions also depend on complete or incomplete PSA.

PMID- 19177832
TI  - [Gigantic ovarian and suprarenal cysts ten years after enucleation of unilateral
      retinoblastoma].
AB  - INTRODUCTION: Retinoblastoma (RB) is the most common eye tumour in children and
      is curable. Patients with hereditary RB have increased risk of developing
      additional tumours, predominantly sarcomas. The published results on the
      treatment of bilateral RB have shown that 10-15% of patients develop second
      primary tumours (SPT). Average latent period, e.g. the period from the diagnosis
      of bilateral RB to the appearance of SPT is 10.4 years. In the literature, the
      appearance of second benign tumours in patients suffering from unilateral and
      bilateral RB has not been analyzed separately. However, the size and the location
      of benign tumours can cause serious complications. CASE OUTLINE: We present a 14
      year-old female patient. At age 4 years, her left eye was enucleated owing to
      unilateral RB. In the postoperative period, she did not undergo irradiation, nor
      did she receive chemotherapy. On her regular ophthalmologic check-up, the patient
      informed us that her belly was "swelling" over the past four months. She had no
      pains or other complaints. The abdomen was significantly above the level of the
      chest, tense, painless on palpation, with obvious fluctuations. Abdominal
      echosonography confirmed the presence of a huge multilocular cystic formation, 19
      x 18 cm in diameter, spreading from the pelvis to the epigastrium, and pressing
      the liver and spleen. A cyst of 4.7 cm in diameter was observed in the upper pole
      of the left kidney. Both the gigantic cyst of the left ovary (weighing 10300 g)
      and the left suprarenal cyst (weighing 30 g) were removed. CONCLUSION: We report
      a patient who developed second non-ocular tumours (ovarian and suprarenal cysts)
      after successful treatment of unilateral RB. Patients treated for RB (hereditary
      and non-hereditary) should be checked regularly and meticulously. Early
      recognition of tumours, treatment can prevent possible complications.

PMID- 19177833
TI  - [Dental caries--therapeutic possibilities].
AB  - Contemporary tendencies in dentistry are based on the concept of maximal
      protection of healthy tooth tissues. Caries removal has been done traditionally
      with mechanical rotary instruments that are fast and precise. However,
      conventional cavity preparation has potential adverse effects to the pulp due to
      heat, pressure and vibrations. Moreover, drilling often causes pain and requires
      local anaesthesia, and these procedures are frequently perceived as unpleasant.
      Etiology, development and prevention of dental caries are better understood today
      and new restorative materials that bond micromechanically and/or chemically to
      dental tissues have been introduced. Thus, development of a new, less destructive
      caries removal technique is allowed. In the last decades, many alternative
      methods have been introduced in an attempt to replace rotary instruments. These
      are claimed to be efficient and selective for diseased tissues and to offer
      comfortable treatment to the patients. New methods include air abrasion, air
      polishing, ultrasonic, polymer burs, enzymes, systems for chemo-mechanical caries
      removal, and lasers. The aim of this paper was to discuss various caries removal
      techniques and possibilities of their use in clinical practice. Based on the
      literature review it can be concluded that none of the new caries removal methods
      can completely replace conventional rotary instruments.

PMID- 19177834
TI  - [Styloid syndrome: a review of literature].
AB  - The American otolaryngologist Eagle was the first to describe styloid syndrome in
      1937. Stylohyoid complex is composed of styloid process, stylohyoid ligament and
      a lesser horn of the hyoid bone. Embriologicaly, these anatomical structures
      originate from Reichert's cartilage of the second brachial arch. In the general
      population, the frequency of the elongated styloid process is estimated to be 4%,
      of which only 4% show clinical manifestations suggesting that the incidence of
      styloid syndrome is 0.16% (about 16,000 persons in Serbia). The styloid process
      deviation causes external or internal carotid impingement and pains which radiate
      along the arterial trunk. Classical stylohyoid syndrome is found after
      tonsillectomy and is characterised by pharyngeal, cervical, facial pain and
      headache. Stylo-carotid syndrome is the consequence of the pericarotid
      sympathetic fibres irritation and compression on the carotid artery. Clinical
      manifestations are found most frequently after head turning and neck compression.
      The diagnostic golden standard for styloid syndrome is 3D CT reconstruction.
      Sagital CT angiography has a leading role in the radiological diagnosis of the
      stylo-carotid syndrome. Differential diagnosis requires the differentiation of
      the styloid syndrome from numerous cranio-facio-cervical painful syndromes. If
      conservative treatment (analgesics, anticonvulsants, antidepressants, and local
      infiltration with steroids or anaesthetic agents) has no effect, surgical
      treatment is applied. Styloid syndrome is underrepresented in neurological
      literature. The syndrome is considered important, because it is clinically
      similar to many other painful cranio-facial syndromes; it is difficult to be
      recognized, and the patient should be treated adequately.

PMID- 19177835
TI  - [A review of current methods in the diagnostics of morphological changes in
      chronic pancreatitis].
AB  - Chronic pancreatitis is a disease with well-defined histopathology, however, the
      diagnosis is not based on the grading of histological changes, but on the
      features registered by the methods of morphological and functional diagnostic
      procedures. The correct diagnosis of chronic pancreatitis is easy in advanced
      stages, but difficult in early stages of the disease. In this review, we present
      the current methods used (echosonography, computer tomography, magnetic
      resonance, endoscopic retrograde cholangiopancreatography, endoscopic
      echosonography) in the diagnostics of chronic pancreatitis.

PMID- 19177836
TI  - Biohybrid devices and encapsulation technologies for engineering a bioartificial
      pancreas.
AB  - The use of cell-based treatments in the field of metabolic organs, particularly
      the pancreas, has seen tremendous growth in recent years. The transplantation of
      islet of Langerhans cells for the treatment of type 1 diabetes mellitus (T1DM)
      has allowed for natural glycemic control for patients plagued with hypoglycemia
      unawareness. The transplantation of islet cells into the portal vein of the
      liver, however, has presented challenges to the survival of the cells due to
      inflammation, vascularization, the need for systemic immunosuppression, and
      physical stress on the graft. New advances in the engineering of appropriate
      biohybrid devices and encapsulation technologies have led to promising
      alternatives to traditional methods.

PMID- 19177837
TI  - The choice of anatomical site for islet transplantation.
AB  - Islet transplantation into the portal vein is the current clinical practice.
      However, it has now been recognized that this implantation site has several
      characteristics that can hamper islet engraftment and survival, such as low
      oxygen tension, an active innate immune system, and the provocation of an
      inflammatory response (IBMIR). These factors result in the loss of many
      transplanted islets, mainly during the first hours or days after transplantation,
      which could in part explain the necessity for the transplantation of islets from
      multiple pancreas donors to cure type 1 diabetes. This increases the burden on
      the limited pool of donor organs. Therefore, an alternative anatomical site for
      islet transplantation that offers maximum engraftment, efficacious use of
      produced insulin, and maximum patient safety is urgently needed. In this review,
      the experience with alternative sites for islet implantation in clinical and
      experimental models is discussed. Subcutaneous transplantation guarantees maximum
      patient safety and has become clinically applicable. Future improvements could be
      achieved with innovative designs for devices to induce neovascularization and
      protect the islets from cellular rejection. However, other sites, such as the
      omentum, offer drainage of produced insulin into the portal vein for direct
      utilization in the liver. The use of pigs would not only overcome the shortage of
      transplantable islets, but genetic modification could result in the expression of
      human genes, such as complement regulatory or "anticoagulation" genes in the
      islets to overcome some site-specific disadvantages. Eventually, the liver will
      most likely be replaced by a site that allows long-term survival of islets from a
      single donor to reverse type 1 diabetes.

PMID- 19177838
TI  - Comparison of the portal vein and kidney subcapsule as sites for primate islet
      autotransplantation.
AB  - To date, the portal vein has been the primary site for clinical islet
      transplantation. Despite success, potential complications such as portal vein
      thrombosis still exist. The kidney subcapsule has been used successfully in
      rodent models of islet transplantation. We hypothesized that the kidney
      subcapsule as a site for islet transplantation in the nonhuman primate model
      would be as effective as the portal vein. Diabetes was induced in the primate
      Macaca fascicularis via a total pancreatectomy. Animals were kept under
      anesthesia during the isolation procedure. Islet isolation was performed using
      intraductal infusion with Liberase HI and mechanical digestion in the Ricordi
      chamber, and were purified using a continuous Ficoll gradient. Purified islets
      were autotransplanted either into the portal vein (n = 6) or the left kidney
      subcapsule (n = 5) of pancreatectomized animals. Intravenous glucose tolerance
      tests were performed prior to pancreatectomy and 10 days following
      transplantation. Three animals underwent pancreatectomy and served as diabetic
      controls. Of the six animals receiving islets in the portal vein, one developed
      portal vein thrombosis. All remaining autotransplanted animals in this group
      remained normoglycemic with glucose-induced insulin secretion that was not
      different from that prior to pancreatectomy. Of the five animals undergoing
      transplantation into the kidney subcapsule, only one maintained normoglycemia and
      elicited insulin secretion in response to glucose stimulation. The other four
      animals remained hyperglycemic. We conclude that the portal vein is superior to
      the kidney subcapsule as a site for islet transplantation in nonhuman primates 10
      days posttransplantation.

PMID- 19177839
TI  - Islet graft response to transplantation injury includes upregulation of
      protective as well as apoptotic genes.
AB  - Pancreatic islets are particularly vulnerable in the initial days after
      transplantation when multiple factors converge to damage the islet graft. The aim
      of this study was to investigate the expression profile of genes involved in
      damage and protection of beta-cells in the initial days after syngeneic islet
      transplantation. We studied the expression of a set of selected genes involved in
      apoptosis (Bcl2, Bclx(L), Bax, Bad, Bid, and CHOP), cytokine defense, (SOCS-1 and
      SOCS-3), or free radical protection (Hmox1, Cu/Zn-SOD, Mn-SOD, and Hsp70).
      Because hyperglycemia has deleterious effects on islet transplantation outcome,
      we studied its effect on the expression of these genes. Five hundred islets were
      syngeneically transplanted under the kidney capsule of normoglycemic or
      streptozotocin-induced diabetic Lewis rats. Gene expression was analyzed by
      quantitative real-time RT-PCR in grafts 1, 3, and 7 days after transplantation,
      and in freshly isolated islets. The expression of proapoptotic genes Bid and
      CHOP, as well as protective genes Bclx(L), Socs1, Socs3, Hmox1, and MnSod, was
      maximally increased 1 day after transplantation, and in most cases it remained
      increased 7 days later, indicating the presence of a protective response against
      cell damage. In contrast, the expression of Bcl2, Bax, Bad, Cu/ZnSod, and Hsp70
      genes did not change. Hyperglycemia did not modify the expression of most studied
      genes. However, MnSod and Ins2 expression was increased and reduced,
      respectively, on day 7 after transplantation to diabetic recipients, suggesting
      that hyperglycemia increased oxidative stress and deteriorated beta-cell function
      in transplanted islets.

PMID- 19177840
TI  - Myoblast xenotransplantation as a tool to evaluate the appropriateness of
      nanoparticular versus cellular trackers.
AB  - Myoblast transplantation is being considered as a potential strategy to improve
      muscle function in myopathies; hence, it is important to identify the
      transplanted cells and to have available efficient reagents to track these cells.
      We first validated a human to mouse xenotransplantation model warranting the
      complete and rapid rejection of the cells. We then used this model to assess the
      appropriateness of a nanoparticle reagent to track the transplanted cells. Human
      myoblasts were loaded with ferrite nanoparticles and injected into the tibialis
      muscle of immunocompetent mice. Upon collection and histological analysis of
      muscle sections at different time points, we observed the total disappearance of
      the human cells within 6 days while ferrite particles remained detectable and
      colocalized with mouse infiltrating and neighboring cells at the injection site.
      These results suggest that the use of exogenous markers such as ferrite
      nanoparticles may lead to false-positive results and misinterpretation of cell
      fate.

PMID- 19177841
TI  - Mesenchymal stem cells for ischemic stroke: changes in effects after ex vivo
      culturing.
AB  - Although ex vivo culture expansion is necessary to use autologous mesenchymal
      stem cells (MSCs) in treating stroke patients, and several researchers have
      utilized culture-expanded cells in their studies, the effects of culture
      expansion on neurogenesis and trophic support are unknown. Thus, we evaluated the
      impact of the passage of MSCs on their effects in a rat stroke model. The i.v.
      application of ex vivo-cultured human MSCs, earlier (passage 2) or later passage
      (passage 6), was performed in a rat stroke model. Behavioral tests,
      immunohistochemical studies, and quantitative analysis using the CAST-grid system
      were performed to evaluate the degree of neurogenesis. We also evaluated the
      levels of trophic factors in both control and MSC-treated rat brain extract.
      Compared to rats that received later-passage human MSCs, behavioral recovery and
      neurogenesis as revealed by bromodeoxyuridine staining were more pronounced in
      rats that received earlier-passage human MSCs (p < 0.01 in both cases). Double
      staining showed that most of the endogenous neuronal progenitor cells, but few
      human MSCs, expressed neuronal and glial phenotypes. Tissue levels of trophic
      factors, including glial cell line-derived neurotrophic factor, nerve growth
      factor, vascular endothelial growth factor, and hepatocyte growth factor, were
      higher in earlier-passage MSC-treated brains than in control or later-passage MSC
      treated brains (p < 0.01 in all cases). Our results indicate that ischemia
      induced neurogenesis was enhanced by the i.v. administration of human MSCs. The
      effects were more pronounced with earlier-passage than with later-passage human
      MSCs, which may be related to the differential capacity in trophic support,
      depending on their passage.

PMID- 19177842
TI  - Hypothalamic proline-rich polypeptide enhances bone marrow colony-forming cell
      proliferation and stromal progenitor cell differentiation.
AB  - The AGAPEPAEPAQPGVY proline-rich peptide (PRP-1) was isolated from neurosecretory
      granules of the bovine neurohypophysis; it is produced by N. supraopticus and N.
      paraventricularis. It has been shown that PRP-1 has many potentially beneficial
      biological effects, including immunoregulatory, hematopoietic, antimicrobial, and
      antineurodegenerative properties. Here we showed that PRP increased colony
      forming cell (CFC) proliferation in rat bone marrow (BM) cells in vivo. In PRP
      treated rat BM, the CFU number at day 7 and day 14 was considerably increased in
      comparison with untreated rat BM and no difference was found at day 21 and day
      28. The related peptide [arg8]vasopressin did not reveal CFC proliferation. PRP
      failed to farther increase CFC proliferation in vitro in BM obtained from PRP
      treated or untreated rats. After 3-4 days of human BM stromal cell cultivation in
      the presence of 2-20 microg/ml PRP the appearance of cells expressing CD15, CD10,
      CD11a, CD11b, CD3, CD4, and CD16 surface antigens did not differ from the
      untreated cells. PRP increased the appearance of CD14-positive cells upon 3-4-day
      incubation with both adult and fetal BM stromal cells. Our results suggest a
      previously undescribed role for the hypothalamic peptide within neurosecretory
      hypothalamus-bone marrow humoral axis, because PRP enhances BM colony-forming
      cell proliferation and stromal cell differentiation.

PMID- 19177843
TI  - Introduction of hIGF-1 gene into bone marrow stromal cells and its effects on the
      cell's biological behaviors.
AB  - Autologous and gene-modified bone marrow stromal cells (MSCs) have shown a bright
      future in clinical applications. However, does a gene-modified MSC still maintain
      its stem cell-like properties? To answer this question, human IGF-1 was
      introduced into rat MSCs using a recombinant retroviral vector and the effects of
      the gene manipulation on the cells' behaviors were investigated. The MSCs
      transfected with hIGF-1 could secrete 6.7-fold higher IGF-1 than the native
      cells. These MSCs had an elevated baseline activity of ERK signaling, an enhanced
      proliferation, increased accumulative numbers of cell doublings, and a reduced
      apoptosis; they showed upregulated expressions of OCT-4, CYP51, and SM22alpha,
      and a downregulated expression of nestin. This indicates that the overexpressed
      IGF-1 enhances the MSCs' self-renewal, endodermal and mesodermal differentiation,
      but weakens their neuronal potential. Although a puromycin selection after hIGF-1
      gene transfection could produce a purer transfected MSC population with stronger
      ability to express functional hIGF-1, it induced premature senescence of the
      selected cells by activating oncogene Ras, leading to a shortened replicative
      life span and a weakened multipotency.

PMID- 19177844
TI  - Establishment of immortalized human hepatocytes by introduction of HPV16 E6/E7
      and hTERT as cell sources for liver cell-based therapy.
AB  - For future cell-based therapies for liver diseases, the shortage of cell sources
      must be resolved. Immortalized human hepatocytes are expected to be among the new
      sources. In addition to telomerase activation by the introduction of human
      telomerase reverse transcriptase (hTERT), inactivation of the p16/RB pathway and/
      or p53 by E6/E7 of human papillomavirus type 16 (HPV16) has been shown to be
      useful for efficient immortalization of several human cell types. Here we report
      the immortalization of human hepatocytes by the introduction of HPV16 E6/E7 and
      hTERT. Human adult hepatocytes were lentivirally transduced with HPV16 E6/E7 and
      hTERT. Two human immortalized hepatocyte cell lines were established and were
      named HHE6E7T-1 and HHE6E7T-2. Those cells proliferated in culture beyond 200
      population doublings (PDs). Albumin synthesis and expression of liver-enriched
      genes were confirmed, but gradually decreased as passages progressed. Karyotype
      analysis showed that HHE6E7T-1 cells remained near diploid but that HHE6E7T-2
      cells showed severe aneuploidy at 150 PDs. Subcutaneous injection of these cells
      into severe combined immunodeficiency (SCID) mice did not induce tumor
      development. Intrasplenic transplantation of dedifferentiated HHE6E7T-1 cells
      over 200 PDs significantly improved the survival of acetaminophen-induced acute
      liver failure SCID mice. In conclusion, we successfully established immortalized
      human hepatocytes that retain the characteristics of differentiated hepatocytes.
      We also showed the reduction of hepatocyte-specific functions in long-term
      culture. However, the results of intrasplenic transplantation to SCID mice with
      acetaminophen-induced acute liver failure showed the possibility of HHE6E7T-1
      serving as a cell source for hepatocyte transplantation.

PMID- 19177845
TI  - Variation in the incidence of teratomas after the transplantation of nonhuman
      primate ES cells into immunodeficient mice.
AB  - Embryonic stem (ES) cells have the ability to generate teratomas when
      transplanted into immunodeficient mice, but conditions affecting the generation
      remain to be elucidated. Nonhuman primate cynomolgus ES cells were transplanted
      into immunodeficient mice under different conditions; the number of transplanted
      cells, physical state (clumps or single dissociated cells), transplant site,
      differentiation state, and immunological state of recipient mice were all varied.
      The tumorigenicity was then evaluated. When cynomolgus ES cells were transplanted
      as clumps into the lower limb muscle in either nonobese diabetic/severe combined
      immunodeficiency (NOD/SCID) or NOD/SCID/gammac(null) (NOG) mice, teratomas
      developed in all the animals transplanted with 1 x 10(5) or more cells, but were
      not observed in any mouse transplanted with 1 x 10(5) cells. However, when the
      cells were transplanted as dissociated cells, the number of cells necessary for
      teratomas to form in all mice increased to 5 x 10(5). When the clump cells were
      injected subcutaneously (instead of intramuscularly), the number also increased
      to 5 x 10(5). When cynomolgus ES cell-derived progenitor cells (1 x 10(6)), which
      included residual pluripotent cells, were transplanted into the lower limb muscle
      of NOG or NOD/SCID mice, the incidence of teratomas differed between the strains;
      teratomas developed in five of five NOG mice but in only two of five NOD/SCID
      mice. The incidence of teratomas varied substantially depending on the
      transplanted cells and recipient mice. Thus, considerable care must be taken as
      to tumorigenicity.

PMID- 19177846
TI  - Severity of occlusal pathologies and associated factors in 12-year-old
      schoolchildren.
AB  - The aim of this study was to estimate the prevalence and severity of occlusal
      pathologies in 12-year-old schoolchildren in Campina Grande, Brazil. The study
      population was composed by 553 12-year-old schoolchildren attending the municipal
      educational system. Information regarding occlusal alterations (Dental Aesthetic
      Index) and subjective perceptions on occlusal pathologies were collected by means
      of structured questionnaires submitted to the students. Bivariate analysis and
      odds ratio were used to determine the existence of association between the
      severity of the occlusalpathologies and the other associated factors. The
      prevalence and severity ofocclusal pathologies were 65.1% (n=360) and 35.1%
      (n=194), respectively The bivariate analysis revealed a positive association
      between the variable "dissatisfaction on smiling related to occlusal problems"
      (OR=1.92 [1.13-3.28]) and the severity of occlusal pathologies. The high
      prevalence and severity of occlusal alterations observed in the present study
      suggests that it is necessary to reformulate the current public oral health
      policies with the inclusion of orthodontic treatment in the set of health
      services provided to the population.

PMID- 19177847
TI  - Alterations of the oral ecosystem in children with celiac disease.
AB  - The aim of this work is to evaluate the alterations of the oral ecosystem in
      symptomatic children with celiac disease (CD), to establish a particular pattern
      of oral markers that can be used as presumptive diagnosis of CD. MATERIAL &
      METHODS: A sample of n=52 children with CD diagnosis according to the modified
      criteria of the European Society of Pediatric Gastroenterology and Nutrition
      (ESPGAN), 1990, was studied. A dental clinical evaluation of soft and hard
      tissues was performed. Saliva samples were obtained; in which buffer capacity,
      total proteins, calcium and phosphate were measured and SDS PAGE 12%
      electrophoretic profiles were performed. In addition, oral mucosa smears were
      collected by brushing. RESULTS: Low frequency of enamel structural alterations
      was found, particularly in the permanent teeth of children with CD. These
      alterations had characteristics of chronological coherence (31.7%), bilateralism
      (26.8%) and symmetry (29.23%). The celiac smears in the celiac group (20%) showed
      signifcant presence of polymorphic nuclei and free nuclei. The celiac group had
      significant differences in buffer capacity, IgA levels, minute volume, calcium
      and Ca/P ratio (p<0.05). The protein profiles of CD children showed the absence
      of bands of low, medium and high molecular weight. CONCLUSION: Our results enable
      us to develop an alteration pattern corresponding to the oral ecosystem of CD
      children. In the CD patients, the most relevant variables were tooth enamel
      alterations, oral mucosa morphology, and modifications of salivary parameters,
      which would enable the dentist to refer these patients to specialist physician.

PMID- 19177848
TI  - Caries, periodontal disease and tooth loss in patients with diabetes mellitus
      types 1 and 2.
AB  - The aim of this work was to determine the frequency of caries, periodontal
      disease and tooth loss in patients affected by diabetes mellitus types 1 and 2.
      It was a cross-sectional study involving 175 subjects distributed in the
      following groups: (1) 35 patients with diabetes type 1 (glycosylated hemoglobin
      values from 6.5%-7%), (2) 35 patients with diabetes type 1 (values of
      glycosylated hemoglobin higher than 7%), (3) 35 subjects without diabetes
      mellitus type 1, (4) 35 patients with diabetes type 2 and (5) 35 subjects without
      diabetes mellitus type 2. The following clinical parameters were evaluated for
      all the subjects who participated in the study: frequency of caries, filled
      teeth, missing teeth, prosthetic restoration, bacterial dental plaque, calculus
      index, probing depth and attachment level. On comparing the groups of patients
      with diabetes type 1 to the control group, there were no statistically
      significant differences among any of the study variables. On comparing the group
      of patients with diabetes type 2 to the control group, there were statistically
      significant differences in the variables missing teeth (p=0.0134), calculus
      (p=0.0001), probing depth (p=0.0009) and attachment level (p=0.0093). The
      variable periodontal disease showed statistically significant dIfferences in the
      group of patients with diabetes type 2. Prevention, supervision and review of the
      oral health of patients with diabetes (types 1 and 2) are needed in order to
      prevent oral alterations.

PMID- 19177849
TI  - Effect of occlusion on joint sounds in asymptomatic individuals.
AB  - Occlusion is a predisposing factor for Temporomandibular Dysfunctions (TMD) of
      the joint, whose first sign and/or symptom is usually joint sound. To verify the
      effect of occlusion on joint sounds, temporomandibular joints (TMJ) were analyzed
      in 78 asymptomatic individuals with various dental conditions. Electrosonography
      was used to determine the intensity of the vibration in the temporomandibular
      joint (TMJ) on opening and closing the mouth. Transducers (piezoelectric
      accelerometer) were placed on the right and left joints. Results were tabled and
      analyzed using the Kruskal-Wallis test (a=0.05). It was concluded that TMJ
      vibration in partly edentulous individuals from Kennedy classes I, II and III is
      statistically higher than in dentate and fully edentulous subjects.

PMID- 19177850
TI  - Survival of Staphylococcus aureus on fomites.
AB  - The aim of this study was to evaluate duration of survival of Staphylococcus
      aureus on contaminated standardized fomites, such as sterilization paper (SP) and
      polyester previously sterilized in a steam autoclave, and to determine the
      potential inhibitory effects of the substrates (fabrics used to manufacture
      garments and special wrapping paper used in the dental setting) using the
      bacteriostasis test. The test was performed on two types of sterile standardized
      samples (T1 and T2). Sterility of the samples was validated following the
      protocol in use at the Department of Microbiology, after which the samples were
      inoculated with 50 microl of a calibrated suspension of Staphylococcus aureus
      (reference strain ATCC 25923) in the exponential growth phase, in a final
      concentration of 10(7) cfu/ml and 10(6) cfu/ml). The samples were incubated at 27
      degrees C and survival and concentration of microorganisms attached to the
      surface of the substrates was determined at the following experimental time
      points: immediately post-contamination, and 3 hours, 24 hours, 3 days, and 7 days
      post-contamination. Recovery was determined and expressed as a percentage; the
      bacteriostasis test was performed and showed negative results. Our results
      suggest that the quantity of recovered microorganisms varies according to the
      type of substrate and that there is a relation between survival and incubation
      time of the inoculated substrate serving as an artificial niche.

PMID- 19177851
TI  - Antimicrobial activity of endodontic sealers based on calcium hydroxide and MTA.
AB  - The aim of this study was to evaluate the antimicrobial activity of a new root
      canal sealer containing calcium hydroxide (Acroseal) and the root canal sealer
      based on MTA (Endo CPM Sealer), in comparison with traditional sealers (Sealapex,
      Sealer 26 and Intrafill) and white MTA-Angelus, against five different
      microorganism strains. The materials and their components were evaluated after
      manipulation, employing the agar diffusion method. A base layer was made using
      Muller-Hinton agar (MH) and wells were made by removing agar. The materials were
      placed into the wells immediately after manipulation. The microorganisms used
      were: Micrococcus luteus (ATCC9341), Staphylococcus aureus (ATCC6538),
      Pseudomonas aeruginosa (ATCC27853), Candida albicans (ATCC 10231), and
      Enterococcus faecalis (ATCC 10541). The plates were kept at room temperature for
      2 h for prediffusion and then incubated at 37 degrees C for 24 h. The results
      showed that Sealapex and its base paste, Sealer 26 and its powder, Endo CPM
      Sealer and its powder, white MTA and its powder all presented antimicrobial
      activity against all strains. Intrafill and its liquid presented antimicrobial
      activity against all strains except P. aeruginosa and Acroseal was effective only
      against M. luteus and S. aureus.

PMID- 19177852
TI  - Cytokines produced by CD4+ T cells against a synthetic GTF-I(1301-1322) peptide
      of Streptococcus mutans in naturally sensitized humans.
AB  - Streptococcus mutans (S. mutans) is the main etiological agent in dental caries.
      Its virulence factors are the proteins PAc and glucosyltransferase (GTF), which
      are related to its physiopathogenia and have been used in research for a dental
      caries vaccine. It was reported that using experimental animal models, GTF-I(1301
      1322) synthetic peptide from the GLU region of the GTFs has Tepitopes, induces
      production of serum antibodies in saliva and reduces the presence of caries, but
      little is known about the cellular response in naturally sensitized humans. The
      aim of this study was to observe whether GTF-I(1301-1322) peptide is capable of
      activating CD4+ T cells in PBMC from naturally sensitized humans, to classify the
      response and to establish the relationship with dental caries. The study was
      conducted on 30 individuals classified into the following 3 groups: active caries
      (AC), History of Caries (HC), and free of caries (H). A blood sample was drawn
      from each individual. Specific antigen stimulation and flow cytometry analyses
      were used to determine cells producing the cytokines IFN-gamma (type 1 cytokine)
      and IL-13 (type 2 cytokine). Cell memory response to GTF-I(1301-1322) peptide was
      found in naturally sensitized humans. Three different responses were detected:
      TH0, TH1, and NR. The percentage of CD4+ T cells producing the cytokines IFN
      gamma (type 1 cytokine) was greater than the percentage producing IL-13
      (p=0.006). No statistically significant differences were found among the three
      groups for the other variables studied (p < or = 0.05). In conclusion, specific
      cellular immune responses against the GTF-I(1301-1322) peptide of S. mutans does
      not differ between individuals who are naturally sensitized, caries- resistant or
      with caries.

PMID- 19177853
TI  - Effect of radiotherapy on the radiopacity and flexural strength of a composite
      resin.
AB  - The aim of this study was to evaluate the effect of radiotherapy on the
      radiopacity and flexural strength of composite resin. Forty Z250 composite resin
      specimens were polymerized using a halogen light-curing unit and divided into 5
      groups, in accordance with the radiotherapy dose: G1- without irradiation, G2- 30
      Gy, G3- 40 Gy, G4- 50 Gy and GS- 60 Gy Digital images were obtained using a GE
      100 X-ray. Radiopacity values were obtained with the Digora digital imaging
      system and the flexural strength was evaluated with an EMIC universal testing
      machine. Data were submitted to ANOVA and Tukey 's test. G1 presented the highest
      radiopacity value, followed by G3, G5, G4 and G2. For flexural strength, G1
      presented the lowest value, followed by G2, G5, G3 and G4. Differences were no
      significant (p>0.05). The commonly used dosage of radiotherapy treatment, did not
      cause alteration in the radiopacity and flexural strength of resin-based
      composites.

PMID- 19177854
TI  - Detection of Porphyromonas gingivalis and Streptococcus intermedius in chronic
      periodontitis patients by multiplex PCR.
AB  - A Multiplex PCR assay for the detection of Porphyromonas gingivalis and
      Streptococcus intermedius in chronic periodontitis is presented. A total of 180
      samples from 65 adults with untreated periodontitis and 17 healthy volunteers
      were taken and processed in a simple boiling step. Cell lysates were used as DNA
      source for multiplex PCR assays. Primers were designed from 16S rRNA gene
      sequences from the GenBank-EMBL database showing specificity for target
      pathogens. This multiplex PCR system could detect 8.2 P gingivalis and S.
      intermedius cells. In untreated periodontitis patients, only 78.5% were positive
      for one or both bacteria; 37% were positive for P gingivalis only, 17% for S.
      intermedius and 24.5% for both. P. gingivalis was detected in 23.5% of healthy
      volunteers, while S. intermedius was not detected in the same patients. The
      distribution of these bacteria was related to the periodontal probing depth,
      while 95.23% of patients with pockets wih 6 to 7 mm deep were positive for either
      or both, only 70.45% of of them with 4 to 5 mm pockets were positive.

PMID- 19177855
TI  - Endodontic microorganism susceptibility by direct contact test.
AB  - The aim of this study was to evaluate in vitro the duration of the antimicrobial
      effect of endodontic sealers by means of the Direct Contact Test. The sealers
      tested were: Endomethasone - Septodont, Endomethasone C-Septodont, Endion-Voco,
      Diaket-ESPE, Pulp Canal Sealer-SybronEndo, and AH26-Dentsply DeTrey. The
      endodontopathic microorganisms (MO) confronted were: Staphylococcus aureus (Sa),
      Candida albicans (Ca), Enterococcus faecalis (Ef), Prevotella intermedia (Pi),
      Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn). Test specimens of
      each sealer were prepared and placed on the surface of agar plates that had been
      inoculated with each MO, and after predetermined periods, transfers were made
      from the contact area between the test specimen and the cultured agar and from
      the area that had not been in contact with the test specimens (control). The
      results were read as presence/absence of microbial growth and analyzed
      statistically using the Kruskal-Wallis test. It was concluded that the structural
      features and virulence of endodontopathic microorganisms determine their response
      to the sealers, independently of the time during which sealers act and the
      mechanism by which the antiseptic reaches the microorganism, which in this case
      was by direct contact.

PMID- 19177856
TI  - Oral and oropharyngeal cancer in a Venezuelan population.
AB  - The aim of this work was to analyze diagnosed cases of Oral Cancer (OC) and
      Oropharyngeal Cancer (OPC) in a Venezuelan population. We clinically evaluated
      130 patients with OC and OPC and a histopathologic diagnosis of squamous cell
      carcinoma. The patients were analyzed according to gender age, and use of alcohol
      and tobacco and the tumors were classIfied based on anatomic location, staging
      parameters, and degree of difFerentiation. Ninety one patients (70%) were male
      and 39 (30%) were female. Patients' age ranged from 26 to 86 years old. Use of
      smoking tobacco, alcohol or both was reported by 84.3%, 49.1% and 45.4% of
      patients, respectively, and was more frequent in males. The most common
      oropharyngeal anatomic location was the base of the tongue (22.3%), followed by
      the tonsils (13.9%), while the most frequently affected oral location was the
      oral tongue (19.2%) followed by the gingiva and alveolar mucosa (10.8%), and the
      floor of mouth (7.7%). The majority of tumors (77.7%) were diagnosed at an
      advanced stage (Stage III or IV); metastasis to the regional lymph nodes occurred
      in 53.1% of cases. According to degree of diferentiation, well, moderately and
      poorly difFerentiated tumors accounted for 45.4%, 46.1% and 8.5% of cases,
      respectively. Well differentiated tumors accounted for 56.7% of OC cases, while
      the majority of OPC cases were classified as moderately or poorly differentiated
      (72.3%) (p < or = 0.002). Also, non-metastatic cases (NO) showed a predominance
      of well-diferentiated tumors (61.2%), while metastatic tumors (N+) were
      classified as moderately or poorly differentiated in 89.8% of cases (p < or =
      0.0001). Our study population was characterized by a predominance of smokers
      and/or drinkers and a predilection for male patients. Most tumors were diagnosed
      at an advanced stage with a high incidence of metastatic spread to the regional
      lymph nodes, indicating possible delays in diagnosis. Less differentiated tumors
      were more frequently encountered among OPC cases and accounted for the vast
      majority of metastatic cases, supporting the prognostic value of assessing the
      degree of difFerentiation.

PMID- 19177857
TI  - Comprehensive attention to oral health in early childhood: a longitudinal
      evaluation of the Infant Clinic Program of the Federal University of Rio Grande
      do Sul, Brazil.
AB  - The Infant Clinic Program believes that oral care should begin within the first
      days of life in order to guarantee good oral health throughout life; however it
      has been observed that many dental professionals are not trained attend to this
      segment of the population. OBJECTIVES: The purpose of the Infant Clinic course is
      to offer the theoretical and practical knowledge that dentists need to know in
      order to offer education, prevention and curative treatments, providing
      comprehensive attention to infants and young children. METHODS: To evaluate the
      effectiveness of this Program, a longitudinal study was conducted with the
      children who participated in the Program during 2004 and 2005. The analysis was
      performed by first defining the profiles of 303 children before they came to the
      Infant Clinic, and comparing their oral status in 2004 and at the end of 2005 (12
      months, Chi-square test, p < 0.01). RESULTS: Of the 303 children observed in
      2004, 72.87% came to the clinic for maintenance of oral health, compared to
      14.83% who had caries lesions. During the first clinical examination (2004), it
      was observed that 57% of the children had good plaque control, while 33% of
      children had poor or very bad plaque control. After 12 months (2005), an increase
      in good plaque control was observed in the children (77.28% with good plaque
      control, and 22.72%poor or very bad plaque control) (p < 0.01). Through the
      treatment of active lesions, we verified a decrease in active lesions (from 82%
      to 32%) (p < 0.01). These results show the effectiveness of the program's
      education, preventive and curative procedures. CONCLUSIONS: In addition to the
      positive experience of the Infant Clinic program, it was concluded that, with the
      support of treatment and parental education regarding healthy diet and oral
      hygiene for children, preventive procedures and curative treatment of existing
      lesions, oral health promotion for very young children was in fact achieved.

PMID- 19177858
TI  - [Ultrasound images for venous puncture and venous access].

PMID- 19177859
TI  - [Preoperative cardiovascular care in noncardiac surgery: what's new in the 2007
      joint guidelines of the American Heart Association and American College of
      Cardiology].

PMID- 19177860
TI  - [Is oxygen therapy truly useful and necessary during elective cesarean section
      under spinal anesthesia?].
AB  - OBJECTIVE: To analyze maternal and fetal well-being with and without the
      application of oxygen therapy. MATERIAL AND METHODS: Randomized trial of full
      term parturients who had received prenatal care during pregnancy. The women were
      healthy and classified as ASA 1. They were scheduled for delivery by cesarean
      section under spinal anesthesia and randomized to 2 groups to breathe room air or
      air providing an inspired oxygen fraction of 40% through a face mask. We assessed
      the well-being of the neonate immediately after birth with the Apgar test and by
      measuring umbilical cord blood gases. RESULTS: One hundred thirty women were
      enrolled. Both groups were similar, with no differences in demographic or
      hemodynamic variables, time from uterine incision to fetal extraction, neonatal
      birth weight, presence of umbilical cord abnormalities, type of resuscitation
      required by the neonate, or Apgar score in the first or fifth minute. Oxygen
      saturation in maternal blood by pulse oximetry was higher after 10 minutes in the
      group of women who received supplemental oxygen through face masks. We also
      observed significant differences in umbilical cord arterial blood between the
      room air and supplemental oxygen groups, respectively, as follows: PaCO2, 51.14
      mm Hg vs 54.33 mm Hg (P=.016); bicarbonate, 22.19 mEq L(-1) vs 23.23 mEq L(-1)
      (P=.012); lactate, 1.85 mmol L(-1) vs 1.64 mmol L(-1) (P=.038). The PO2 in venous
      blood also differed significantly: 25.53 mm Hg vs 28.13 mm Hg, respectively
      (P=033). CONCLUSIONS: Breathing supplemental oxygen or not during elective
      cesarean delivery of healthy parturients under spinal anesthesia does not have a
      significant effect on neonatal well-being.

PMID- 19177861
TI  - [Central venous pressure, rewarming time, and total fluid replacement volume are
      predictors of mortality and complications after cardiac surgery].
AB  - OBJECTIVE: To analyze the influence of early (first day) postoperative factors on
      postoperative course in patients who have undergone heart surgery. PATIENTS AND
      METHODS: A cross-sectional study of consecutively enrolled heart surgery patients
      was designed. We recorded central venous pressure, time required for rewarming to
      a core temperature of 35.5degrees C, and total fluids administered in 24 hours.
      We then analyzed their influence on mortality and cardiac, pulmonary, and renal
      complications. RESULTS: Two hundred thirty-six patients were included. Central
      venous pressure over 18 mm Hg, time to rewarming over 6 hours, and administration
      of more than 5 L of fluids in the first 24 hours were factors associated with
      increased mortality and the development of cardiovascular, pulmonary, and renal
      complications. CONCLUSIONS: Central venous pressure, rewarming time, and fluid
      replacement volume required on the first day are predictors of postoperative
      course.

PMID- 19177862
TI  - [Continuous interscalene block for analgesia following shoulder rotator cuff
      repair: evaluation of 2 bupivacaine concentrations applied with the same infusion
      technique].
AB  - OBJECTIVE: To evaluate postoperative analgesia and patient satisfaction with the
      continuous interscalene block using 2 bupivacaine concentrations in combination
      with sufentanil for patients undergoing shoulder rotator cuff repair surgery.
      MATERIAL AND METHODS: Prospective trial in 43 patients randomized to 2 groups.
      Group 1 received 0.125% bupivacaine plus 1 microg mL(-1) of sufentanil in
      continuous infusion at a rate of 7 mL h(-1). Group 2 received an infusion of
      0.0625% bupivacaine plus 1 microg mL(-1) of sufentanil at the same rate. Pain was
      assessed on a visual analog scale (VAS) 2, 4, 6, 12, 24, and 48 hours after
      surgery. Intravenous ketoprofen and morphine were used to provide rescue
      analgesia. Morphine and bupivacaine consumption, degree of satisfaction, and the
      incidence of adverse effects were recorded. RESULTS: Forty-three patients (21 in
      group 1 and 22 in group 2) were enrolled. Postoperative VAS scores, morphine
      consumption, and satisfaction were similar in the 2 groups. Bupivacaine
      consumption was lower in group 2 (P<.005). CONCLUSIONS: Both the tested
      bupivacaine concentrations for the continuous interscalene block provided similar
      levels of analgesia after shoulder rotator cuff repair surgery. Reducing the
      bupivacaine concentration to 0.625% decreased the consumption of local anesthetic
      without diminishing the quality of analgesia.

PMID- 19177863
TI  - [Ultrasound-guided puncture of the jugular vein using a posterior approach].
AB  - BACKGROUND: Ultrasound-guided central venous catheterization provides a direct
      view of anatomical structures, making it easier to determine the exact puncture
      site, thereby reducing the associated mechanical complications. PATIENTS AND
      METHODS: This study included patients scheduled for central venous
      catheterization. An ultrasound examination was performed on the necks of all
      patients before the right internal jugular vein was catheterized by a single
      operator using ultrasound monitoring. RESULTS: We studied 21 men and 14 women;
      the mean (SD) age of the patients was 53 (17) years. Forty percent were kidney
      transplant recipients and 57% had had the right internal jugular vein
      catheterized on other occasions. The carotid artery had accidentally been
      punctured using the standard catheterization technique in 4 of the patients; the
      internal jugular vein was then catheterized successfully using ultrasound
      guidance, which clearly showed the hematoma caused by the carotid puncture. The
      right internal jugular vein was successfully catheterized in 34 patients; it was
      necessary to catheterize the left jugular vein in 1 patient as the ultrasound
      examination revealed thrombosis of the right vein. A single puncture was
      performed in all cases and none of the complications associated with venous
      puncture were observed. CONCLUSION: Ultrasound images allowed us to effectively
      examine the jugular vein prior to puncture for central venous catheterization.
      Ultrasound-guided puncture of the vein was satisfactory and free from
      complications in all cases.

PMID- 19177864
TI  - [Evaluation of a continuous positive airway pressure system without a ventilator
      to treat acute respiratory failure in children].
AB  - OBJECTIVE: Noninvasive continuous positive airway pressure (CPAP) is widely used
      in pediatric patients with acute respiratory failure. However, the lack of
      specific interfaces and appropriate ventilators and poor tolerance of the
      technique by these patients can lead to failure of the application. The aim of
      this study was to analyze the efficacy of a CPAP system using a modified Mapleson
      breathing circuit during acute respiratory failure in pediatric patients.
      MATERIAL AND METHODS: We performed a prospective observational study in children
      with acute respiratory failure in whom noninvasive ventilation was indicated.
      CPAP was applied through a Mapleson D circuit fitted with a manometer and a
      nasopharyngeal tube as the interface. Heart rate, respiratory rate, inspired
      oxygen fraction (FiO2), PaO2, PaCO2, and pulse oximetry were measured before
      treatment and after 2 hours of treatment. RESULTS: Sixteen patients with a mean
      age of 3.8 years were studied for a period of 18 months. We observed a mean (SD)
      change in PaCO2 from 66.8 (18.08) mm Hg to 46.48 (5.9) mm Hg after CPAP (P=.16)
      and a mean change in the PaO2/FiO2 ratio from 201 (111) to 262 (115) after CPAP
      (P=.30). The mean heart rate fell from 156 (22) beats/min to 127 (18) beats/min
      (P=.05) and the mean respiratory rate from 53 (15) breaths/min to 33 (13)
      breaths/min (P<.05). No severe complications were recorded and tolerance was
      satisfactory. The technique was considered a success in 12 patients (75%).
      CONCLUSIONS: CPAP without a ventilator, through a Mapleson D circuit, can be used
      with a high success rate to provide noninvasive ventilation for pediatric
      patients with acute respiratory failure.

PMID- 19177865
TI  - [Anesthetic considerations in primary immunodeficiencies].
AB  - Primary immunodeficiencies are a group of mostly hereditary, or congenital,
      disorders. Some cases, however, show no hereditary pattern despite an evident
      familial distribution. The incidence of these cases is variable and the most
      frequent of them is immunoglobulin A deficiency. Many are pediatric disorders
      that are occasionally so serious that the patient does not survive the first year
      of life due to the development of systemic infections. In other cases, survival
      is much longer and it is possible to find adult carriers in routine clinical
      practice. These are less aggressive cases that form part of specific clinical
      syndromes that must be recognized so that appropriate anesthetic management can
      be planned. We review the clinical characteristics of primary immunodeficiencies
      that may be relevant to anesthetic management in these patients.

PMID- 19177866
TI  - [Pneumomediastinum and extensive subcutaneous emphysema after normal labor].
AB  - Spontaneous pneumomediastinum associated with subcutaneous emphysema is a rare,
      though life-threatening, complication of late pregnancy and labor. We report the
      case of a primipara who, after undergoing normal labor and delivery of a normal
      weight baby, developed pneumomediastinum and extensive subcutaneous emphysema
      with significant symptoms within minutes of delivery. This peripartum
      complication is usually self-limiting when the aggravating factors are no louguer
      present. Management includes strict monitoring of the patient and conservative
      treatment of symptoms.

PMID- 19177867
TI  - [Trapped epidural catheter: reconstruction of computed tomography images].
AB  - A trapped epidural catheter without a knot is a rare complication. During
      placement of an epidural catheter for analgesia during labor, resistance made it
      impossible to position the catheter within the epidural space. A second catheter
      was inserted to provide the required analgesia. When the second catheter was
      removed, computed tomography (CT) revealed that the tip of the first catheter was
      close to the the right facet joint space. A second attempt to extract the
      catheter failed. In light of this situation, the patient was seated with the
      spine slightly bent to one side, a guidewire was inserted through the catheter
      lumen, and the catheter and guidewire were gently pulled; the catheter was
      extracted without causing the tip to break up. Three-dimensional CT
      reconstruction allowed the catheter tip and characteristics of the joint surfaces
      to be observed. We discuss protcols and alternative strategies that can be
      followed when an epidural catheter is difficult to remove, including the most
      appropriate images to use for guidance.

PMID- 19177868
TI  - [Thyroid cyst puncture during central venous catheterization: a rare
      complication].

PMID- 19177869
TI  - [General anesthesia in a patient with POEMS syndrome].

PMID- 19177870
TI  - [Prolonged intubation due to a cervical hematoma after accidental carotid artery
      puncture].

PMID- 19177871
TI  - [Intranasal midazolam for central venous catheterization of an anxious patient
      without a peripheral venous access].

PMID- 19177872
TI  - [Echocardiographic diagnosis of internal jugular vein thrombosis].

PMID- 19177873
TI  - [Anesthesia for cesarean section in a patient with limb-girdle muscular
      dystrophy].

PMID- 19177874
TI  - [Ultrasound to insert a central venous catheter: thrombus in the jugular vein].

PMID- 19177875
TI  - [Chance diagnosis of a spinal tumor after lumbar puncture for spinal anesthesia].

PMID- 19177876
TI  - [On the third debut of lumbar epidural anesthesia in Spain: 1940-1950].

PMID- 19177877
TI  - [Meningococcal purpura fulminans].

PMID- 19177878
TI  - Good riddance!

PMID- 19177879
TI  - Crime causes the wealth gap.

PMID- 19177880
TI  - Medical responsibility at inquests.

PMID- 19177881
TI  - Training an old-timer as a GP in Britain.

PMID- 19177882
TI  - New health ministers--so little time, so much to do.

PMID- 19177883
TI  - Science seals Mbeki/Msimang's AIDS ignominy.

PMID- 19177884
TI  - Vital breast cancer drugs highlight funding ethics.

PMID- 19177885
TI  - DOH reviews HIV/TB treatment protocols.

PMID- 19177886
TI  - Accounting for the full benefits of childhood vaccination in South Africa.

PMID- 19177887
TI  - Free provision of PEP and medical advice for sexual offence victims: what should
      doctors do?

PMID- 19177888
TI  - Epiploic appendagitis.

PMID- 19177889
TI  - Primary central nervous system lymphoma: an unusual presentation.

PMID- 19177890
TI  - Preventing thromboembolism in medical inpatients--time to catch up with the
      surgeons?

PMID- 19177891
TI  - Accuracy of patients' self-reporting of pregnancy and awareness of risks to the
      fetus from X-ray radiation.

PMID- 19177892
TI  - Haemodialysis access by inferior vena cava catheterisation.

PMID- 19177893
TI  - Knowledge of post-rape procedures and guidelines among first-year female resident
      students at the University of the Free State.

PMID- 19177894
TI  - Do knees survive the Comrades Marathon?
AB  - OBJECTIVE: To detect by magnetic resonance imaging (MRI) the presence and type of
      knee injuries in non-professional runners after running an ultra-marathon, and to
      determine whether ultra-marathon running exacerbates pre-existing knee injuries
      or results in new permanent injuries. DESIGN: A prospective MRI study of one knee
      of 10 randomly selected participants who completed the Comrades Marathon between
      1997 and 2002. Their knees were scanned 48 hours before the race, and 48 hours
      and 1 month after the race. SETTING: All scans were performed at the Radiology
      Department, Wentworth Hospital, Durban, and the University of KwaZulu-Natal. MAIN
      OUTCOME MEASURES: Scores of all knee injuries detected on MRI scans immediately
      before the race, compared with the scores after the race. RESULTS: All scanned
      knees demonstrated an abnormal amount of joint fluid before the race; this
      increased immediately after the race in 5 runners and remained unchanged in
      another 5. At 1 month, 5 knees showed decreased joint fluid and 5 remained
      unchanged, but these were not the same runners as in the post-race groups. There
      was increased signal intensity in the distal patellar and quadriceps tendons in 4
      runners before the race, which increased or remained the same on post-race scans
      in 6 knees. There was a decrease in signal intensity on scans taken 1 month later
      in 3 runners, with complete resolution in 2 and no change in 1. Old injuries to
      ligaments, tendons or other knee structures were unaffected by the race. No bone
      bruising, cartilage defects or meniscal abnormalities were observed. There was no
      significant difference in the pre- and post-race or 1-month scan scores.
      CONCLUSIONS: The race appears to have had a detrimental effect on runners who
      started the ultra-marathon with tendinopathy, which worsened post-race by MRI
      criteria. One month after the race, the scan appearance of the overuse injury had
      either improved or resolved completely. Bone bruising or meniscal damage did not
      appear to occur, and the presence of increased joint fluid probably relates to
      stress or injury.

PMID- 19177895
TI  - Fetal alcohol syndrome among grade 1 schoolchildren in Northern Cape Province:
      prevalence and risk factors.
AB  - OBJECTIVE: To describe the prevalence, characteristics and risk factors for fetal
      alcohol syndrome (FAS) and partial FAS among schoolgoing children in Grade 1 in
      Northern Cape Province, South Africa. DESIGN: A cross-sectional study using a two
      tiered method for ascertainment of FAS/partial FAS cases, comprising: screening
      of growth parameters, diagnostic assessment for screen-positive children using
      clinical and neurocognitive assessments, and maternal history of drinking during
      pregnancy. Mothers or caregivers of FAS children and matched controls were
      interviewed. SETTING: Primary schools in De Aar (8) and Upington (15). Subjects.
      Grade 1 pupils in 2001 (De Aar, N=536) and 2002 (Upington, N=1299). OUTCOME
      MEASURES: FAS or partial FAS. RESULTS: The prevalence of FAS/partial FAS was
      high: 64/536 (119.4/1000, 95% CI 93.2-149.9) in De Aar, and 97/1299 (74.7/1 000,
      95% CI 61.0-90.3) in Upington. Overall, 67.2 per 1000 children (95% CI 56.2-79.7)
      had full FAS features. Growth retardation was also common in this population:
      66.6% (1181/1774) were underweight, 48.3% (858/1776) stunted, and 15.1% had a
      head circumference <2 SD for age. Mothers of children with FAS were less likely
      to have full-time employment or have attended secondary school and had lower body
      mass index, and about 80% currently smoked. Over two-thirds of all pregnancies
      had been unplanned. CONCLUSIONS: A very high proportion of pupils (nearly 1 in
      10) had FAS/partial FAS, the rate in De Aar being the highest yet described in
      South Africa. FAS/partial FAS may contribute to the extremely high rate of growth
      retardation in South Africa as a whole and is a major cause of learning
      disability. These epidemiological features are important in designing preventive
      interventions.

PMID- 19177896
TI  - Clinical profile and predictors of severe illness in young South African infants
      (<60 days).
AB  - BACKGROUND: Most childhood deaths occur within the first 2 months of life. Simple
      symptoms and signs that reliably indicate the presence of severe illness that
      would warrant urgent hospital management are of major public health importance.
      OBJECTIVES: To describe the disease profile of sick young infants aged 0-59 days
      presenting at King Edward VIII Hospital, Durban, and to assess the association
      between clinical features assessed by primary health workers and the presence of
      severe illness. METHODS: Specific clinical signs were evaluated in young infants
      by a health worker (nurse), using a standardised list. These signs were compared
      with an assessment by an experienced paediatrician for the need for urgent
      hospital- or clinic-based care. RESULTS: Nine hundred and twenty-five young
      infants were enrolled; 61 were <7 days old, 477 were 7-27 days old, and 387 were
      28-59 days old. Illnesses needing urgent hospital management in the age group <7
      days were hyperbilirubinaemia (43%) and sepsis (43%); in the age group 7-27 days
      they were pneumonia (26%), sepsis (17%) and hyperbilirubinaemia (15%), and in the
      age group 28-59 days they were pneumonia (54%) and sepsis (15%). The clinical
      sign most consistently predictive of needing urgent hospital care across all
      groups was not feeding well. Among those over 7 days old, a history of difficult
      feeding, temperature 237.5 degrees C and respiratory rate > or =60 per minute
      were also important. CONCLUSIONS: The simple features of feeding difficulties,
      pyrexia, tachypnoea and lower chest in-drawing are useful predictors of severity
      of illness as well as effective and safe tools for triaging of young infants for
      urgent hospital management at primary care centres. Neonatal hyperbilirubinaemia,
      pneumonia and sepsis are the common conditions for which young infants require
      urgent hospital-based management.

PMID- 19177897
TI  - Neuropathic pain in AIDS patients prior to antiretroviral therapy.
AB  - OBJECTIVE: To measure the prevalence, severity and morbidity of neuropathic pain
      in AIDS patients, prior to the initiation of antiretroviral (ARV) therapy.
      DESIGN: A prospective, cross-sectional and descriptive-analytical study. SETTING:
      The Kalafong Hospital HIV Clinic in Pretoria. SUBJECTS: All patients with
      confirmed AIDS who were referred to the Kalafong HIV clinic to be initiated on
      ARV therapy during the period August 2006 to March 2007. OUTCOME MEASURES: Data
      were collected regarding the presence and severity of neuropathic pain in each
      subject. Pain of predominantly neuropathic origin (POPNO) was identified using
      the Neuropathic Pain Diagnostic Questionnaire (DN4). Numerical rating scales
      (NRS), adapted from the Brief Pain Inventory, were used to measure pain severity
      and pain-related interference with six aspects of daily living. RESULTS: Of the
      354 patients studied, 20.9% (95% confidence interval (CI) 16.8-25.2%) had POPNO.
      This pain was significantly more frequent in patients who were male, had lower
      CD4+ counts or higher viral load levels, and those on TB treatment. Eighty per
      cent of patients with POPNO experienced significant pain (worst pain severity >
      or =5 out of 10 on a NRS). Pain-related interference was highest for enjoyment of
      life, mood and ability to work. There was a significant positive correlation
      between severity of pain and pain-related interference for all domains of daily
      living evaluated. CONCLUSIONS: POPNO results in significant suffering and
      impaired functioning in patients with AIDS. It is therefore imperative that
      clinicians assess patients with AIDS for the presence and severity of neuropathic
      pain and manage it, using the most recent evidence-based guidelines.

PMID- 19177898
TI  - Quantitative determination of cucurbitacin E and cucurbitacin I in homoeopathic
      mother tincture of Gratiola officinalis L. by HPLC.
AB  - "Hedgehyssop" Gratiola officinalis L. (Scrophulariaceae) is found as an
      ingredient in homeopathic remedies. Among the active compounds found in G.
      officinalis, the cucurbitacines constitute a group of triterpenoid substances
      which are well-known for their bitterness and toxicity. Due to the toxicity of
      the cucurbitacin's aglycones it becomes necessary to determine the content of the
      aglycones and glycosides that may be responsible for the pharmacological activity
      and toxicity in homeopathic tinctures according to the European Pharmacopeia
      guidelines. In this context a HPLC method was developed for the identification
      and determination of cucurbitacin E and I in homeopathic mother tinctures. To
      evaluate the total concentration of the aglycones, cucurbitacin E and I formed
      after hydrolysis we determined the concentration of both compounds after
      enzymatic hydrolysis with beta-glucosidase in vitro. Reversed-phase HPLC with a
      Eurospher C18 column with precolumn and acetonitrile-water gradient system as the
      mobile phase proved to be suitable for direct determination of both aglycons,
      cucurbitacin E and I in Gratiola-mother tinctures. The contents of cucurbitacin
      E, cucurbitacin I, cucurbitacin E glycoside and cucurbitacin I glycoside were
      found as 0.0065%, 0.0031%, 0.0011% and 0.0006%, respectively in Gratiola-mother
      tincture prepared according to method 2a HAB.

PMID- 19177899
TI  - Enantioseparation of chiral sulfoxides using teicoplanine chiral stationary
      phases and kinetic study of decomposition in human plasma.
AB  - Teicoplanin chiral stationary phases (CHIROBIOTIC TAG and CHIROBIOTIC T) used in
      this study are suitable for enantioseparation of chiral sulfoxides in polar
      organic phase mode. The method involves determination of chiral sulfoxides in
      human plasma on teicoplanin chiral stationary phase after the off-line SPE pre
      treatment using OASIS HLB cartridges. The limit of determination was in the range
      of 0.004-0.026 microg/ml for individual racemic mixtures. The S(+) enantiomeric
      form eluted always as the first, except the 4-(methyl sulfinyl) biphenyl with
      less retained R(-) enantiomer. It was found that the rate constants of individual
      chiral sulfoxides depend on the type of halogen substituent. There was no
      significant difference in rate constants considering the position of Cl
      substitution on aromatic ring of sulfoxides. Moreover, the rate constants of R(-)
      and S(+) forms of enantiomers are significantly different just in the case of 4
      fluoro phenyl sulfoxide.

PMID- 19177900
TI  - LC-MS and LC-PDA vs. phytochemical analysis of Colchicum brachyphyllum.
AB  - In this paper, reliability and validity of a recently in-house developed
      dereplication strategy based on LC-MS and LC-UV/Vis PDA techniques were verified.
      The dereplication strategy was applied to investigate the alkaloid rich fraction
      of Colchicum brachyphyllum Boiss. & Haussk. ex Boiss. (Colchicaceae) which has
      been previously analyzed phytochemically. Both studies results, LC-MS and LC-PDA
      and phytochemical analysis, were matched in seven compounds namely: (-)
      colchicine (5), 3-demethyl-(-)-colchicine (4), (-)-cornigerine (7), beta-lumi-(-)
      colchicine (6), (-)-demecolcine (3), 3-demethyl-(-)-demecolcine (2), and 2,3
      didemethyl-(-)-demecolcine (1). LC-MS and LC-PDA based dereplication strategy was
      not able to detect two of the compounds that were reported in the phytochemical
      study namely: (+)-demecolcinone and (-)-androbiphenyline. This finding could
      raise a question about the "naturality" of (+)-demecolcinone. On the other hand
      apigenin (8) was identified only using this dereplication strategy. Four
      compounds which had molecular ions at m/z 372 and 400 in the stems, and at m/z at
      372 and 358 in flowers, could not be dereplicated, and were thus considered
      unknown. Their spectral data were not matched with neither the compounds that
      have been isolated previously from this species nor with any other colchicinoid;
      hence they should be pursued as potential new compounds.

PMID- 19177901
TI  - Investigation of drug loading and in vitro release mechanisms of insulin-lauryl
      sulfate complex loaded PLGA nanoparticles.
AB  - Insulin, a water soluble peptide hormone, was hydrophobically ion-paired with
      sodium lauryl sulfate (SDS) at the stoichiometric molar ratio of 6:1. The
      obtained insulin-SDS complex precipitation was subsequently formulated in
      biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles by a
      modified spontaneous emulsion solvent diffusion method. Compared with a
      conventional method for free insulin encapsulation, direct dissolution of SDS
      paired insulin in the non-aqueous organic phase led to an increase in drug
      recovery from 42.5% to 89.6%. The more hydrophobic complex contributes to the
      improved affinity of insulin to the polymer matrix, resulting in a higher drug
      content in the nanoparticles. The drug loading was investigated by determining
      initial burst release at the first 30 min. The results showed that 64.8% of
      recovered drug were preferentially surface bound on complex loaded nanoparticles.
      The in vitro drug release was characterized by an initial burst and subsequent
      delayed release in dissolution media of deionized water and phosphate buffer
      saline (PBS). Compared with that in PBS, nanoparticles in deionized water medium
      presented very low initial burst release (15% vs. 65%) and incomplete cumulative
      release (25% vs. 90%) of the drug. In addition, dialysis experiments were
      performed to clarify the form of the released insulin in the dissolution media.
      The results suggested that the ion-pair complex was sensitive to ionic strength,
      insulin was released from the particular matrix as complex form and subsequently
      suffered dissociation from SDS in buffer saline. Moreover, the in vivo
      bioactivity of the SDS-paired insulin and nanoparticulate formulations were
      evaluated in mice by estimation of their blood sugar levels. The results showed
      that the bioactivity of insulin was unaltered after the ion-pairing process.

PMID- 19177902
TI  - Influence of formulation properties on chemical stability of captopril in aqueous
      preparations.
AB  - The influence of various formulation properties on the chemical stability of
      captopril in aqueous media at pH 3 was investigated, in order to reformulate and
      increase the shelf-life of an oral mixture of the drug. At this pH, chemical
      stability is improved by an increase in drug concentration (1-5 mg/ml) and a
      decrease in temperature (5-36 degrees C), the latter demonstrated by a linear
      Arrhenius-plot. The activation energy is low (Ea = 10.2 kcal/mol), thus the Q10
      value is only 1.8 in pure aqueous solutions. The degradation at the lowest
      concentration investigated in pure aqueous solution apparently follows zero order
      kinetics. The reaction order is changed at higher concentrations. We are
      presenting a hypothesis of intramolecular proton transfer from the thiol to the
      ionized carboxylic group as the initial step in the oxidative degradation
      pathways of captopril. Long-term stability of 1 mg/ml captopril in aqueous
      solutions at pH 3, stored at 36 degrees C for one year, shows that the sugar
      alcohol sorbitol accelerates degradation of the drug while Na-EDTA at a
      concentration as low as 0.01% is sufficient to stabilize these samples. Purging
      with N2-gas prior to storage is not essential for drug stability, as long as Na
      EDTA is present. Only at a low level of Na-EDTA (0.01%) combined with a high
      level of sorbitol (35%), purging with N2-gas appears to have a small effect. The
      destabilizing effect of sugar alcohols is confirmed by accelerated degradation
      also in the presence of glycerol. The efficient stabilization in the presence of
      Na-EDTA at a low concentration indicates that the metal-ion-catalyzed oxidation
      pathway dominates the chemical degradation process at low pH, although several
      mechanisms seem to be involved depending on excipients present.

PMID- 19177903
TI  - Preparation and characterization of modified lipid nanoparticles for doxorubicin
      controlled release.
AB  - Low drug encapsulation efficiency and burst release are the main drawbacks of
      lipid nanoparticles. To solve these problems, lipid nanoparticles containing a
      cross-linked lipid network were prepared in this study. Monostearin (MS) and
      octadecylamine (ODA) were used as the solid lipids, and oleic acid (OA) was used
      as liquid lipid. The use of a small amount of ODA was to form cross-linked
      network by glutaraldehyde in the presence of OA. Using doxorubicin (DOX) as a
      model drug, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC)
      and glutaraldehyde cross-linked NLC were prepared. The physicochemical properties
      of these lipid nanoparticles such as average diameter, drug loading, drug
      encapsulation efficiency and in vitro drug release were investigated. The drug
      loading capacities and encapsulation efficiency were improved by mixing OA with
      the solid lipids to produce the nanoparticle matrix, and were further increased
      by the cross-linking of glutaraldehyde. The faster drug release was obtained when
      the NLC with higher OA content. After cross-linking by glutaraldehyde, the burst
      release of DOX from NLC could be reduced, in comparison to both SLN and non cross
      linked NLC. The results indicated the NLC with cross-linked network are a
      potential drug delivery system with improved drug encapsulation and controlled
      drug release.

PMID- 19177904
TI  - Characterization of multidrug resistance-associated protein mRNAs expression
      profiles in Caco-2 and HT-1080 cell lines induced by methotrexate.
AB  - An efflux function induced by multidrug resistance-associated proteins (MRPs)
      contributes to the mechanisms of resistance to methotrexate (MTX). Since it has
      been reported that the human Caucasian colon adenocarcinoma cell line (Caco-2)
      shows high MRPs expression, it is assumed that Caco-2 cells are resistant to MTX.
      Alternatively, the human fibrosarcoma cell line (HT-1080) has been reported to be
      highly sensitive to MTX. In this study, the difference in the growth-inhibitory
      activity of MTX in these cell lines was compared as a characteristic of
      sensitivity. Subsequently, the characterization of MRP (1-8) mRNAs expression
      profiles before and after MTX exposure in these cell types was examined with the
      multiplex reverse-transcription-polymerase chain reaction (RT-PCR) method. It was
      demonstrated that the expressions of MRP2, MRP3, MRP6, and MRP8 mRNAs in the HT
      1080 cells were lower than those in the Caco-2 cells and that only MRP5 mRNA
      expression was induced in the Caco-2 cells after MTX treatment. The MRP mRNAs
      expression profiles between these two cell lines could be differentiated widely.
      The characterization of MRPs profiles might be associated with resistance to MTX
      in cells. Additionally, this multiplex RT-PCR method would be beneficial for
      further time-dependence investigations of the MRP mRNAs expression profiles.

PMID- 19177905
TI  - Tocotrienol and alpha-tocopherol reduce corticosterone and noradrenalin levels in
      rats exposed to restraint stress.
AB  - This study investigates the effects of tocotrienol (TT) or alpha-tocopherol (TF)
      supplementation on corticosterone level, noradrenalin level and gastric lesions
      in rats exposed to restraint stress. Twenty-four male Sprague Dawley rats were
      randomly assigned into 4 equally sized groups; two control groups were given
      olive oil, while the treated group was supplemented with either tocotrienol of
      tocopherol orally at a dose of 60 mg/kg body weight. After 28 days of treatment,
      one control group, TT group and TF group were subjected to restraint stress, 2
      hours daily for 4 consecutive days. After the last exposure to stress, plasma
      samples were taken to determine the corticosterone and noradrenalin levels, after
      which the rats were sacrificed. The stomach was excised for the evaluation of
      gastric lesions. Our findings showed that TT and TF were able to maintain the
      corticosterone level to the prestress values, while only TT was able to maintain
      the noradrenalin level in rats exposed to stress. Tocotrienol was found to be
      better in preventing formation of gastric lesions compared to TF. As a
      conclusion, the protective effect of vitamin E was related to the ability to
      inhibit stress induced elevation of corticosterone and noradrenalin levels.

PMID- 19177906
TI  - Transrepression and transactivation potencies of inhaled glucocorticoids.
AB  - The anti-inflammatory activity of inhaled glucocorticoids is primarily mediated
      through transrepression of pro-inflammatory transcription factors such as AP-1
      and NF-kappaB, while systemic side effects are largely attributed to
      transactivation via glucocorticoid response elements (GRE) in the promoter region
      of responsive genes. The objective of this study is to investigate whether
      inhaled corticosteroids exhibit differences in their transactivation and
      transrepression potencies. A549 human alveolar epithelial type II like cells,
      stably transfected with a reporter plasmid containing an AP-1, NF-kappaB or GRE
      induced secreted alkaline phosphatase reporter gene (SEAP), were exposed to a
      panel of concentrations of the six inhaled and three systemic glucocorticoids.
      Glucocorticoid-induced changes in SEAP expression were quantified by
      chemiluminescence. For eight glucocorticoids (budesonide, desisobutyryl-cicle
      sonide, dexamethasone, flunisolide, fluocortolone, fluticasone propionate,
      mometasone furoate, prednisolone) the EC50 for NF-kappaB mediated transrepression
      was significantly larger than that for both transactivation and transrepression
      via AP-1. For the remaining glucocorticoid (triamcinolone acetonide), it was
      greater than that for transactivation. It is concluded that, within the studied
      cell system, inhaled corticosteroids did not exhibit preferential
      transrepression, but had higher potencies for transactivation than for
      transrepression via NF-kappaB and had differential potencies for the two
      transrepression pathways.

PMID- 19177907
TI  - Comparison of effects of some cyclic chalcone analogues on selected mitochondrial
      functions.
AB  - In earlier studies, cytotoxity of chalcones (1) and cyclic chalcone analogues E-2
      arylidene-tetralones (2) and -benzosuberones (3) towards various murine and human
      tumour cells has been tested. Preliminary biochemical investigations showed the
      compounds to inhibit protein and DNA syntheses. It was also found that the
      compounds affect the cellular thiol status of the treated cells. In order to gain
      new insights into the cytotoxic mechanism of the compounds effects of some
      previously investigated 2 and 3 derivatives on isolated rat liver mitochondria
      was investigated. It was found that the most cytotoxic compounds 2c and 3b
      significantly decreased the GSH level of the mitochondria. Incubation of the
      investigated chalcones with reduced GSH under cell-free conditions indicated
      spontaneous conjugation (non-redox) reaction at pH 7.4 and pH 9.0. Investigation
      of antioxidant capacity of the compounds by monitoring time course of the Fenton
      reaction initiated in vitro degradation of 2-deoxyribose showed the compounds to
      display hydroxyl radical scavenger activity. Investigation of respiratory control
      ratio of 2c and 3b showed the compounds to display an inhibitory effect on
      respiration, compound 2b, however, displayed rather an uncoupling effect. The
      experiments provide further details of cytotoxic effects of the synthetic
      chalcones displaying dual - cytotoxic and cytoprotective - effects.

PMID- 19177908
TI  - Synergistic immunostimulatory effect of pidotimod and red ginseng acidic
      polysaccharide on humoral immunity of immunosuppressed mice.
AB  - We investigated the synergistic effect of pidotimod and red ginseng acidic
      polysaccharide (RGAP) from Panax ginseng C.A. Meyer on humoral immune response
      challenged by lipopolysaccharide (LPS) and sheep red blood cells (SRBC) in
      immunosuppressed mice. Combined treatment with pidotimod and RGAP significantly
      increased the number of plaque-forming cells in the spleen in response to both
      LPS and SRBC, while treatment with either pidotimod or RGAP individually had no
      such effect. IgG levels in serum were augmented for secondary responses to SRBC
      in co-treated mice, but not in mice treated with either drug alone. Microscopic
      studies revealed that architecture of the spleen, thymus, and lymph nodes was
      conserved. GPT and creatinine in serum as indicators of hepatic and renal
      functions showed no difference compared to the control group. These results
      indicate that combined treatment with pidotimod and RGAP has an immunostimulatory
      effect in a synergistic manner on antibody response to challenge with LPS and
      SRBC without toxic changes.

PMID- 19177910
TI  - Improvement of the etodolac purity test by reversed phase high-performance liquid
      chromatography.
AB  - The resolution of etodolac by reversed phase HPLC applied in the European
      Pharmacopeia (EP) was found to be greatly affected by using methanol as the
      injection solvent and the system of gradient elution, which leads to peak
      broadening as well as poor separation of etodolac from the impurities such as 2
      (7-ethylindol-3-yl) ethanol respectively. Changing the type of injection solvent
      (methanol) by the mobile phase, which is a mixture of methanol, buffer (KH2PO4,
      PH = 7), and acetonitril as well as monitoring the gradient program (increasing
      the polarity) leads to enhance the selectivity and efficiency of the analysis of
      etodolac by eliminating the peak broadening and markedly improving the separation
      of etodolac from 2-(7-ethylindol-3-yl) ethanol. The method was validated by
      parameters such as selectivity, repeatability, and intermediate precision.

PMID- 19177911
TI  - Induction of hepatic peroxisomal beta-oxidation of fatty acids by
      dehydroepiandrosterone (DHEA) in male F-344 rats.
AB  - Pharmacological administration of dehydroepiandrostenone (DHEA, 300 mg/kg, p.o.)
      for 2 weeks significantly increased (P < 0.01) the activity of hepatic
      peroxisomal beta-oxidation of fatty acids in male F-344 rats. Similar effects
      were observed following 8 week administration of DHEA. These results are
      discussed in the light of oxidative stress-mediated hepatocarcinogenesis.

PMID- 19177909
TI  - Identification and determination of the intra- and extracellular aminopeptidase
      activity by synthetic L-Ala-, L-Tyr-, and L-Phe-beta-napthylamide.
AB  - A simple, rapid and straightforward procedure for identification and
      determination of intracellular and extracellular activity of aminopeptidases
      employing synthetic substrates beta-naphtylamides of L-Ala, L-Phe, and L-Tyr was
      used. Poppy cells (Papaver somniferum L.) permeabilized by Tween 80 were
      immobilized via crosslinking by glutaraldehyde. Glutaraldehyde immobilized poppy
      cells lost their viability and demonstrated significantly lower aminopeptidase
      activities than untreated control cells probably due to a damage to the enzyme
      active centre. Poppy cells immobilized by pectate and alginate have retained high
      activity of studied aminopeptidases. The culture medium (without cells) used for
      the identification and determination of extracellular enzyme activities retained
      20-21%, whereas intracellular activities were estimated to be 79-80% of total
      enzyme activity. Thus the intracellular specific activity was 1.00-1.07 higher.

PMID- 19177912
TI  - Walter Krosche (1882-1957) and the Mannich reaction.
AB  - Walter Krosche was the Ph.D. student of Carl Mannich, with whom the latter
      published the school forming paper where the first 'Mannich reaction' has been
      described. For the first time biographic details and photos of Krosche are
      published here in a short biographic sketch.

PMID- 19177913
TI  - [Serious and sometimes fatal consequences of high-altitude pulmonary oedema].
AB  - Three women aged 25, 34 and 22 years respectively, experienced high-altitude
      pulmonary oedema during a climbing holiday. The first patient presented with
      complaints arising from a fast ascent to high altitude and was treated with
      acetazolamide and rapid descent. She recovered without any complications. The
      second patient developed symptoms during the night, which were not recognised as
      high-altitude pulmonary oedema. The next morning she died while being transported
      down on a stretcher without having received any medication or oxygen. The third
      case was not a specific presentation of high-altitude pulmonary oedema but
      autopsy revealed pulmonary oedema. This woman had already been higher up on the
      mountain before she developed complications. The cases illustrate the seriousness
      of this avoidable form of high altitude illness. The current Dutch national
      guidelines advise against the use of medication by lay people. A revision is
      warranted: travellers to high altitude should be encouraged to carry
      acetazolamide, nifedipine and corticosteroids on the trip. Travel guides ought to
      be trained to use these drugs. In addition climbing travellers should be
      encouraged to adopt appropriate preventive behaviour and to start descending as
      soon as signs of high-altitude pulmonary oedema develop.

PMID- 19177914
TI  - [The practice guideline 'Children with fever' (second revision) from the Dutch
      College of General Practitioners; a response from the perspective of general
      practice].
AB  - The new version of the practice guideline 'Children with fever' has recently been
      published by the Dutch College of General Practitioners. There is no evidence to
      support antipyretic therapy in children with fever. Paracetamol (acetaminophen)
      is not advised for preventing seizures, but may be given to relieve other
      symptoms. Parents have a different attitude towards fever than do GPs. Parents
      are concerned about serious causes or complications of the fever. However, GPs
      are more interested in parameters other than fever. The practice guideline
      recommends that parents be advised and reassured, but also stresses that parents'
      concerns be considered as potential predictors of serious illness. Missed urinary
      tract infections can be a serious cause of fever. Therefore, urine should be
      examined in children younger than 2 years who are feverish with no apparent
      cause. Unfortunately, the guideline does not identify tropical diseases as a
      differential diagnosis. Finally, doctors must be alert to the possibility of
      dehydration. The complexity of identifying dehydrated children is discussed.

PMID- 19177915
TI  - [The practice guideline 'Children with fever' (second revision) from the Dutch
      College of General Practitioners; a response from the perspective of
      paediatricians].
AB  - The new version of the practice guideline 'Children with fever' was recently
      published by the Dutch College of General Practitioners and is commented on from
      the perspective of paediatricians. Whether or not general practitioners should
      refer feverish children to the paediatrician depends on the age of the patient
      and the severity of the illness. All children younger than 1 month and children
      with warning symptoms should be referred to a paediatrician at once. One of the
      warning symptoms is that the child gives the impression of being seriously ill at
      the physical examination. As it can be difficult to ascertain the severity of the
      illness and to distinguish which children will develop a serious bacterial
      infection, observation scales can be of use, as can the general practitioner's
      intuitive feeling that 'something is wrong'. Emphasis is put on the fact that
      infections are dynamic processes and therefore good follow-up is important.
      Children under the age of 2 years with a fever with no apparent cause should be
      re-examined after 24-48 h. Parents should be properly instructed to come back for
      re-examination of their child if the clinical picture changes or worsens.

PMID- 19177916
TI  - [Delirium in the intensive care unit].
AB  - Delirium is a common condition in the intensive care unit (ICU). Between 16-89%
      of all ICU patients experience an episode of delirium during admission. Several
      detection tools have been developed for use specifically in the ICU. The
      Confusion Assessment Method for the intensive care unit (CAM-ICU) and the
      Intensive Care Delirium Screening Checklist (ICDSC) combine high sensitivity with
      high specificity. Treatment consists of treatment of underlying disorders,
      nonpharmacological measures and symptomatic drug therapy. The prognosis for ICU
      patients who experience delirium is worse than for those who do not. Delirious
      patients are more likely to develop complications, spend longer in hospital and
      have a higher mortality rate. In view of the high frequency, poor prognosis, high
      costs and lack of studies into the treatment of ICU delirium, research into the
      possibilities for prevention, early detection and treatment of the condition is
      essential.

PMID- 19177917
TI  - [Perianal fistulas: developments in the classification and diagnostic techniques,
      and a new treatment strategy].
AB  - The aim of surgical treatment of perianal fistulas is to treat the patient's
      symptoms, with low recurrence rates and risk of incontinence. In recent years
      there have been developments regarding the classification and diagnosis
      ofperianal fistulas. MRI is the most appropriate diagnostic tool. In the hands of
      an experienced operator anal endosonography is a suitable, less expensive and
      readily-available alternative. As a result of developments in fistula surgery it
      is now more practical to classify perianal fistulas as low or high fistulas, as
      this has implications for the further treatment. Low perianal fistulas are
      defined as fistulas of which the fistula tract is located in the lower third of
      the external anal sphincter. High fistulas are fistulas in which the fistula
      tract runs through the upper two-thirds of the external sphincter muscle. Low
      perianal fistulas can be treated safely by fistulotomy. At present, rectal
      advancement is the gold standard for the surgical treatment of high
      transsphincteric perianal fistulas. The anal fistula plug might be an alternative
      for the treatment of high transsphincteric perianal fistulas.

PMID- 19177919
TI  - [Diagnostic image (400). A woman with a smooth tongue surface. Pernicious
      anaemia].
AB  - A 49-year-old woman with exertional dyspnoea had a pale skin and an atrophic
      tongue due to pernicious anaemia.

PMID- 19177918
TI  - [Summary of the practice guideline 'Children with fever' (Second Revision) from
      the Dutch College of General Practitioners].
AB  - In the second revision of the practice guideline 'Children with fever' from the
      Dutch College of General Practitioners, due to its greater reliability rectal
      measurement of the body temperature above measurement with an ear thermometer is
      recommended in the case of children younger than 3 months, where the classical
      signs of infectious diseases are often less apparent. The practice guideline
      distinguishes between alarm signs which can be recognised by the parents and
      alarm symptoms which can be diagnosed by the physician during a physical
      examination. In children younger than 2 years who are feverish with no apparent
      cause, the urine should be examined at the first consultation. An X-ray of the
      thorax of a child with fever is only necessary if pneumonia is suspected. As it
      is not possible at an early stage to identify serious cases among children who
      are feverish without an apparent cause, these children should be re-examined
      within 24-48 hours. Children with fever who are younger than 3 months should be
      referred to a paediatrician. A typical febrile seizure is harmless, nevertheless
      an underlying meningitis should be excluded.

PMID- 19177920
TI  - [Infant mortality and births in the 19th and early 20th centuries].
AB  - During the 19th century infant mortality was very high in the Netherlands,
      particularly in the provinces of South Holland and Zeeland (up to 300 per 1000
      live births and more), and also in parts of North Brabant and Limburg. In the
      northern provinces (Drenthe, Groningen and Friesland) mortality was lower. Where
      breast-feeding was infrequently given (in rural areas of South Holland, Zeeland
      and from the 1850s also in North Brabant), infant mortality was relatively high.
      In the northern provinces many mothers breast-fed their infants. The fertility
      rate of married women was high, especially in those parts of the country where
      breast-feeding was infrequent. From 1875-1880 fertility rate and infant mortality
      decreased: the so-called demographic transition. Improved social conditions and
      employment opportunities played an important role in this as did the vertical
      social mobility: limitation of the size of families gave children opportunities
      to climb the social ladder.

PMID- 19177921
TI  - [From gene to drug: recent developments in medicinal chemistry].
AB  - The development ofa new drug often takes more than ten years. Until recently,
      researchers were obliged to carry out experimental research on the efficacy of
      variants of those molecules of which the effect was known. It took a long time
      before a structure-activity relationship could be established. Currently, the
      full effect of the stormy developments in the Life Sciences, including the
      sequencing of the human genome, has not yet been fully felt in clinical practice.
      However, in laboratories researching medicinal products, the technology and the
      strategies being applied are changing drastically. Understanding disease
      processes and pharmaconprotein interactions at molecular level make it possible
      to develop biologically active pharmaceuticals using efficient developmental
      techniques involving crystallography and computer models. At the same time it is
      becoming clear that more research is necessary in order to understand the
      pharmacokinetic characteristics and toxicological activity of medicines under
      development. This second phase in the development of medicinal products too, is
      being strongly stimulated by the recent changes.

PMID- 19177922
TI  - [Pleural empyema, chirurgeons and Auenbrugger's Inventum novum].
AB  - In the past while the diagnosis was primarily made by the physician, the
      treatment of thoracic empyema was a surgeon's job. Carrying out this treatment
      was something of a hit and miss affair. With the change from belief in the
      Hippocratic principles ofhumours towards organs and tissues being the cause of
      disease, the way diagnoses were made also changed. The technique of percussing
      the thorax developed by Auenbrugger two centuries ago, was the beginning of
      diagnosing based on meticulous physical examination. Chirurgeons were expected to
      treat thoracic empyema adequately and by employing this technique, were able to
      make a more exact diagnosis and consequently provide better treatment. Modern
      imaging techniques have rendered manual thoracic percussion less often necessary.
      Percussion is now carried out much more often by pulmonologists than by surgeons.
      Nevertheless, Auenbrugger's 'inventum novum' will continue to be a gratefully
      employed technique.

PMID- 19177923
TI  - [Development of concepts of disease, diagnostics and neurosurgical treatment of
      brain tumours in The Netherlands (1890-1950)].
AB  - The history of the treatment ofbrain tumours in the Netherlands begins around
      1890. From this time up to 1950, following other European countries and later the
      United States, the conceptualization, diagnostics, and surgical treatment of
      brain tumours changed dramatically. New morphological classifications were
      introduced, as well as technical innovations in the fields ofimaging diagnostics
      and surgical methods. At the same time, the common view ofclinical signs ofbrain
      tumours changed into the concept that symptoms were caused by increased
      intracranial pressure. As is the case today, the innovations in Dutch
      neurosurgery in the first half of the 20th century were based on the interaction
      between techniques, knowledge and clinical experiences.

PMID- 19177924
TI  - [Influenza vaccination now from 60 years of age onwards].

PMID- 19177926
TI  - [Successful clinical basic research].

PMID- 19177925
TI  - [Every year 100 women in Sweden are unnecessarily stricken by cervix cancer].

PMID- 19177927
TI  - [Anatomy of the placebo effect. Sham acupuncture in IBS shows three components of
      the placebo effect].

PMID- 19177928
TI  - [Response to placebo can potentiate medical treatment. Be aware--and influence-
      the patient's attitude to the treatment].

PMID- 19177929
TI  - [Ablation as first line therapy in supraventricular tachycardias. Good results
      and few complications in a study of 2 207 consecutive patients].

PMID- 19177930
TI  - [Condyloma typing important for follow up of HPV vaccination. A condyloma
      reporting project].

PMID- 19177931
TI  - [Physical activity can save patients with psychosis from the metabolic syndrome].

PMID- 19177932
TI  - [Registration of care course indicates potential organ donors. The registration
      tool Donor Action tested in the Southern health care region].

PMID- 19177933
TI  - [Raynaud phenomenon as adverse effect of ADHD treatment].

PMID- 19177934
TI  - [Is there a reason to take the cholesterol deniers seriously?].

PMID- 19177935
TI  - [Too much antibiotics when physicians don't use ear microscopes].

PMID- 19177936
TI  - [Toxicity risks of local anesthetics administered to small children].

PMID- 19177937
TI  - [Is prenatal diagnosis a non-issue for the National Board of Health and
      Welfare?].

PMID- 19177938
TI  - [Psychiatry is a specialty on diseases of the human psyche].

PMID- 19177939
TI  - [Mb Schnitzler in Sweden--yet another case].

PMID- 19177940
TI  - [The old surgeon's script is living medical history].

PMID- 19177941
TI  - Issues in Law & Medicine. Preface.

PMID- 19177942
TI  - Can Glucksberg survive Lawrence? Another look at the end of life and personal
      automony.
AB  - In Washington v. Glucksberg, the Court declined to find a right to physician
      assisted suicide ("PAS") in the Constitution. Not a single Justice dissented. One
      would expect such a ruling to be quite secure. But Lawrence v. Texas, holding
      that a state cannot make consensual homosexual conduct a crime, is not easy to
      reconcile with Glucksberg. Lawrence certainly takes a much more expansive view of
      substantive due process than did Glucksberg. It is conceivable that the five
      Justices who made up the Lawrence majority--all of whom still sit on the Court-
      might overrule Glucksberg. For various reasons, however, this seems improbable.
      Unlike the situation with respect to the pre-Lawrence era, Glucksberg does not
      stigmatize any politically vulnerable group. When there is no democratic defect
      in the political process, there is much to be said for courts deferring to
      reasonable legislative judgments. Moreover, unlike the developments preceding
      Lawrence, there has been no emerging awareness of a right or liberty to enlist
      the assistance of a physician in committing suicide. No state supreme court has
      found a right to PAS in its own state constitution. Nor, in the decade since
      Glucksberg, has any state legislature legalized PAS. And attempts have been made
      to do so in some twenty states. In addition, various considerations might cause a
      court to balk at constitutionalizing PAS for the terminally ill. Such a right is
      not easily cabined. If personal autonomy extends to the time and manner of one's
      death, why doesn't it also apply whenever a competent person believes that death
      is better than continued life? Once the right to PAS is grounded on self
      determination or personal autonomy in controlling one's own life and death, it no
      longer seems plausible to limit it to the terminally ill. Why should people who
      have to endure pain, suffering, or indignity for a much longer time than the
      terminally ill (often defined as those with six months or less to live) be denied
      this right? The argument made by many proponents of PAS that the right to forgo
      medical treatment and the right to PAS are merely subcategories of the same broad
      right is not convincing. Most of the two million people who die every year in
      this country do so in hospitals and long-term care institutions and do so after a
      decision to forgo life-sustaining treatment has been made. If medical treatment
      could not be rejected, vast numbers of patients would be at the mercy of every
      technological advance. (For example, Nancy Cruzan could have been kept alive in
      her persistent vegetative state for thirty years.) Allowing a patient to die at
      some point is a practical condition upon the successful operation of medicine.
      The same can hardly be said of PAS.

PMID- 19177943
TI  - Physician-assisted suicide in Oregon: a medical perspective.
AB  - This article examines the Oregon Death with Dignity Act from a medical
      perspective. Drawing on case studies and information provided by doctors,
      families, and other care givers, it finds that seemingly reasonable safeguards
      for the care and protection of terminally ill patients written into the Oregon
      law are being circumvented. The problem lies primarily with the Oregon Public
      Health Division ("OPHD"), which is charged with monitoring the law. OPHD does not
      collect the information it would need to effectively monitor the law and in its
      actions and publications acts as the defender of the law rather than as the
      protector of the welfare of terminally ill patients. We make explicit suggestions
      for what OPHD would need to do to change that.

PMID- 19177944
TI  - Other people's lives: reflections on medicine, ethics, and euthanasia.

PMID- 19177945
TI  - 2007 C. H. McCloy Lecture: "Field of Dreams:" sport as a context for youth
      development.

PMID- 19177946
TI  - The influence of matching populations on kinematic and kinetic variables in
      runners with iliotibial band syndrome.
AB  - The purpose of this study was to assess how participant matching influences
      biomechanical variables when comparing healthy runners and runners with
      iliotibial band syndrome (ITBS). We examined 52 healthy runners (CO) and 18 with
      ITBS, using three-dimensional kinematics and pressure distribution. The study
      population was matched in three ways and compared with the biomechanical
      findings: ITBS versus CO I (unmatched), ITBS versus CO II (matched to gender) and
      ITBS versus CO III (matched to gender height, and weight). The final number of
      participants in each group was n = 18. The kinematic variables showed a
      dependency on the matching process. The largest statistically significant
      differences (after Bonferroni adjustment) in the frontal and transverse planes
      were between ITBS and CO III (p = .008). Pressure measurements were also
      dependent on the matching process, with decreasing and nonsignificant differences
      (p = .006) between ITBS and CO after refining the process (ITBS vs. CO III). The
      results of this study and the necessity of matching seem to be plausible (lever
      arms, different running styles). Data matching is important for understanding
      overuse injuries in running.

PMID- 19177947
TI  - Sedentary activity and body composition of middle school girls: the trial of
      activity for adolescent girls.
AB  - This study describes the relationships between sedentary activity and body
      composition in 1,458 sixth-grade girls from 36 middle schools across the United
      States. Multivariate associations between sedentary activity and body composition
      were examined with regression analyses using general linear mixed models. Mean
      age, body mass index, and percentage of body fat were 12.0 +/- 0.51, 21.1 kg/m2
      +/- 4.8, 28.5 +/- 8.9, respectively. Girls averaged 7.7 +/- 1.2 sedentary hours
      per day and about 13 hr (approximately 97% of the day) of both sedentary and
      light activities. Overweight girls were significantly more (13 min; p < .003)
      sedentary, especially after school (> 2 p.m.; p < .01), and less physically
      active (p < .0001) than normal weight girls. The study documents small but
      significant associations between sedentary activity and adiposity.

PMID- 19177948
TI  - Predicting performance on a firefighter's ability test from fitness parameters.
AB  - The purpose of this project was to identify the relationships between various
      fitness parameters such as upper body muscular endurance, upper and lower body
      strength, flexibility, body composition and performance on an ability test (AT)
      that included simulated firefighting tasks. A second intent was to create a
      regression model that would predict firefighter performance on the test. Thirty
      eight experienced firefighters performed the AT and underwent assessments for the
      fitness parameters. Multiple regression analyses indicated that variation in the
      fitness parameters explained a significant, F(6, 36) = 6.31, p < .001, proportion
      (55%) of the variation observed in the AT. The results demonstrated that upper
      muscular strength and endurance as well as low body composition were
      significantly related (p < .01) to better performances on the simulated
      firefighting tasks. Variables such as low back and hamstring flexibility, upper
      and lower body strength, and body composition may contribute significantly to the
      model's predictive power.

PMID- 19177949
TI  - Auditory model: effects on learning under blocked and random practice schedules.
AB  - An experiment was conducted to determine the impact of an auditory model on
      blocked, random, and mixed practice schedules of three five-segment timing
      sequences (relative time constant). We were interested in whether or not the
      auditory model differentially affected the learning of relative and absolute
      timing under blocked and random practice. Participants (N = 80) were randomly
      assigned to one of eight practice conditions, which differed in practice schedule
      (blocked-blocked, blocked-random, random-blocked, random-random) and auditory
      model (no model, model). The results indicated that the auditory model enhanced
      relative timing performance on the delayed retention test regardless of the
      practice schedule, but it did not influence the learning of absolute timing.
      Blocked-blocked and blocked-random practice conditions resulted in enhanced
      relative timing retention performance relative to random-blocked and random
      random practice schedules. Random-random and blocked-random practice schedules
      resulted in better absolute timing than blocked-blocked or random-blocked
      practice, regardless of the presence or absence of an auditory model during
      acquisition. Thus, considering both relative and absolute timing, the blocked
      random practice condition resulted in overall learning superior to the other
      practice schedules. The results also suggest that an auditory model produces an
      added effect on learning relative timing regardless of the practice schedule, but
      it does not influence the learning of absolute timing.

PMID- 19177950
TI  - Gait transitions of persons with and without intellectual disability.
AB  - This study examined whether the walk-to-run transition speed (W-RTS) and the run
      to-walk transition speed (R-WTS) were different or more variable between
      participants with and without intellectual disability (ID). Nine adults with ID
      and 10 adults without ID completed in a series of walk-to-run and run-to-walk
      trials on a treadmill. W-RTS and R-WTS were identified using force-sensitive
      resistors. When transition speeds were expressed as Froude numbers to account for
      differences in leg length, W-RTS was slower and intraindividual variability of W
      RTS and R-WTS was greater in participants with ID. These findings support the
      idea that the unique constraints of individuals with ID result in altered
      attractor dynamics for walking and a weaker coupling between locomotor speed and
      order parameters governing gait transitions.

PMID- 19177951
TI  - National physical education standards: a summary of student performance and its
      correlates.
AB  - This study was one of the first to examine elementary student performance on the
      first four national standards for physical education (National Association for
      Sport and Physical Education, 2004). Motor skill competency, strategic knowledge,
      physical activity, and physical fitness measures were collected from fourth- and
      fifth-grade students (N = 180) in the midwestern United States. Students
      demonstrated difficulty in attaining all four standards, particularly physical
      activity. Both personal demographics and physical attributes influenced
      performance. In particular gender was a correlate of motor competency. Although
      the expectations may not be attainable at given times because of developmental
      differences, the study results provide some support for the value of guiding
      students to competency in all standards, as opposed to a single expectation.
      These findings also suggest continued use of the standards as a framework for
      physical education. Further research is warranted to explain student performance
      levels and develop effective methods for competency.

PMID- 19177952
TI  - Classroom teachers' perceptions of the impact of barriers to teaching physical
      education on the quality of physical education programs.
AB  - A major aim of the current study was to determine what classroom teachers
      perceived to be the greatest barriers affecting their capacity to deliver
      successful physical education (PE) programs. An additional aim was to examine the
      impact of these barriers on the type and quality of PE programs delivered. This
      study applied a mixed-mode design involving data source triangulation using
      semistructured interviews with classroom teachers (n = 31) and teacher-completed
      questionnaires (n = 189) from a random sample of 38 schools. Results identified
      the key factors inhibiting PE teachers, which were categorized as teacher-related
      or institutional. Interestingly, the five greatest barriers were defined as
      institutional or out of the teacher's control. The major adverse effects of these
      barriers were evident in reduced time spent teaching PE and delivering PE lessons
      of questionable quality.

PMID- 19177953
TI  - Squat jump performance during growth in both sexes: comparison with cycling
      power.
AB  - The purpose of this cross-sectional study was to investigate leg muscle power and
      compare two activities (jumping and cycling) in 383 girls and 407 boys ages 9-19
      years. Results in anthropometric characteristics and jumping performance were
      comparable until midadolescence, and sex differences were observed. Lean leg
      volume (LLV) was the reason for most of the variance (76% in girls and 88% in
      boys) in jumping performance. However the LLV exponent was higher than expected
      in boys but not girls. Therefore, unidentified qualitative changes of muscle
      function during growth in boys must be considered. The squat jump index (SJI) was
      highly correlated to cycling peak power (CPP; N = 790, r = .94, p < .001).
      Although prediction error of CPP from SJI was less than 5% when considering each
      sex-and-age group, individual errors mounted to 40%. Due to its practicability,
      SJI is recommended in large-scale developmental prospective studies. However,
      cycling and jumping protocols are not interchangeable when measuring peak power
      values.

PMID- 19177954
TI  - Active and passive commuting to school: influences on affect in primary school
      children.
AB  - Active commuting among school children is being encouraged for physical and
      environmental reasons, but little is known about its influence on affect. The aim
      of this study was to test the hypothesis that children who walk further to school
      experience increased arousal and affective valence compared with children who
      walk a short distance. This was assessed with the children's feeling scale (CFS)
      and children's felt arousal scale (CFAS). Distance walked to school and affective
      change between home and school were assessed over a 2-week period in 99 children
      between 5 and 10 years of age. Home to school differences in CFS and CFAS scores
      were compared in children who walked a short (100-300 m); medium (301-500 m), and
      long distance (over 500 m). Although differences were not always statistically
      significant, there was evidence that the children who walked further reported a
      greater increase in their CFAS scores between home and school (average eta2 =
      .08, range: .01-.15) and, to a lesser extent, in their CFS scores (eta2 = .04,
      range: .002-.06). Further research is needed to explore whether there is an
      optimum walking distance and the contribution of other factors, especially social
      contacts during commuting, the environment, and the weather.

PMID- 19177955
TI  - The effect of an acute after-school exercise bout on percentage of body fat using
      leg-to-leg bioelectrical impedance analysis in children.

PMID- 19177956
TI  - A comparison of supply and demand for PETE faculty: the changing landscape.

PMID- 19177957
TI  - My patients are hurting, are yours?

PMID- 19177958
TI  - Why science?

PMID- 19177959
TI  - Fortune cookies are often right.

PMID- 19177960
TI  - Raising dental IQs.

PMID- 19177961
TI  - Oral Pathology Quiz #61. Case number 1. Actinic cheilitis.

PMID- 19177962
TI  - Oral Pathology Quiz #61. Case number 2. Mucous membrane pemphigoid.

PMID- 19177963
TI  - Percent of NJ children with dental and medical visits is one of the highes in the
      country, but...
AB  - The percent of New Jersey children with dental and medical visits is one of the
      highest in the country, but the state is just average in a comparative ranking of
      health system performance of all states and the District of Columbia. The state
      fares better in other rankings which include personal behavior, community
      environment, public health policies and health outcomes. The major areas of
      approval and concern are highlighted. Ranking states by a series of health and
      social dimensions provides an opportunity to "take stock" of ongoing developments
      as well as provide a standard for comparative purposes. The following
      presentation reviews a series of recent state rankings that serves as a follow-up
      to an earlier report in this Journal when New Jersey ranked 19th. (Note: 1st is
      best, 51st is worst)

PMID- 19177964
TI  - My point of view Dentist Bill of Rights.

PMID- 19177965
TI  - The expectations of pregnant women regarding antenatal care.
AB  - From a feminist perspective, research on childbirth and women's health is a means
      to a positive change that is conducted in partnership with women for their
      benefit. A patient-led National Health System (NHS) (Hillan, 1999) also calls for
      consultation with patients and the wider public for shaping the current and
      future health services. This study was aimed at exploring and describing the
      expectations that pregnant women have regarding antenatal care service by the
      midwife practitioner. In-depth interviews were conducted in an antenatal unit of
      an Academic Hospital in Gauteng Povince. Data saturation was reached with a
      sample of eighteen pregnant women who were conveniently selected. Data analysis
      ran concurrently with data collection. A manual content analysis as described by
      Tesch was used. Lincoln and Guba's method of ensuring trustworthiness was adopted
      (Lincoln & Guba, 1985:328) Literature was undertaken to compare the findings of
      this study with those of other previous studies. Women displayed several common
      expectations that led to the saturation of data. It also became apparent from the
      findings that each woman had varied expectations. There were also some
      commonalities within the women's expectations. Health care, as the major
      expectation and a basic human right, appeared to be basically fulfilled, with the
      exception of interactional characteristics such as the communication of
      information, guidance, involvement, the understanding and explanation of aspects,
      freedom of choice, punctuality, individualized care and continuity of care. The
      conclusions that were reached let to recommendations for nursing practice,
      education, research and the formulation of guidelines for the midwife
      practitioner for the implementation of effective antenatal care, based on the
      identified expectations.

PMID- 19177966
TI  - The acceptability, knowledge and perceptions of pregnant women toward HIV testing
      in pregnancy at Ilembe District.
AB  - This research study aimed to investigate the acceptability, knowledge and
      perceptions of pregnant women toward HIV testing in pregnancy in Ilembe District.
      An exploratory research design guided the study. A systematic random sampling was
      used to select pregnant women who were attending the ante-natal clinic for the
      first time in their current pregnancy. Self-administered questionnaires with
      close-ended questions were used in the collection of data. The questions included
      the women's demographic details, their views of HIV testing, knowledge and as
      well as their acceptability of HIV testing. Forty questionnaires were distributed
      and they were all returned. A quantitative method was used to analyse the data.
      The findings of the study revealed that 45 % of the women in the sample were
      relatively young (18-25 years) and most of them (90%) were unmarried .The
      majority of women (92.5%) said testing was a good idea and 85% said it was
      necessary. However only 52.5% said they would opt for HIV testing. The uptake of
      HIV testing was found to be low. Eighty-seven and a half percent (87.5%) of the
      women in the sample were of the opinion that HIV testing in pregnancy was of
      benefit to the mother and her baby. Women in the study were generally found to
      have a good understanding and good perceptions towards HIV testing in pregnancy,
      but this was not consistent with their behaviour.

PMID- 19177967
TI  - Knowledge of pregnant women on transmission of HIV infection through breast
      feeding.
AB  - Although breast-feeding is nature's way of providing nutrition to the baby, in
      HIV positive mothers this has been identified as one of the means through which
      HIV infection is transmitted from the mother to the child. In Africa where
      children under the age of 5 are killed by preventable diseases like diarrhoea,
      the issue of HIV transmission through breast feeding poses an added huge problem.
      Research has, however shown that exclusive infant feeding, be it breast or
      formula, reduces the risk substantially. It is imperative that mothers be
      informed about safer methods of infant feeding so that HIV infection is kept to a
      minimum. The objective of the study was to explore and describe the knowledge
      that pregnant women had about mother to child transmission of HIV infection
      through breast-feeding. A non-experimental quantitative exploratory and
      descriptive research design was used to explore the knowledge women had on mother
      to child transmission of HIV infection through breast-feeding. From the data
      collected, it showed that although women were aware of the susceptibility of
      children to HIV infection if fed on breast and formula feeds simultaneously by
      HIV positive mothers, exclusive feeding was a problem as people associated the
      practise with a positive HIV status. Women who had not disclosed their HIV status
      and were HIV positive, found it difficult to comply with the requirement to
      exclusively feed their infants. These either continued with complementary feeds
      or did not collect the free formula milk supply preferring instead to buy the
      formula feeds privately. In this study it was recommended that information on
      transmission of HIV infection from mother to child through breast -feeding
      including the benefits of exclusive infant feeding, be it breast or formula, for
      the first three to six months be provided to the community so that relatives can
      support the mother on infant feeding method of choice.

PMID- 19177968
TI  - HIV/AIDS risk factors among residence students at the University of the Free
      State.
AB  - The aim of this study is to investigate the sexual campus culture of students at
      the University of the Free State (UFS), by specifically focussing on gender and
      culture as patterns of high-risk sexual behaviour. The sample consisted of 396
      participants, 211 female and 185 male students, with a mean age of 19.9 years.
      Sixty one percent (61%) of the students associated themselves with a Western
      cultural background and 39% with an African cultural background. In this article
      an exposition is provided on information collected in a survey conducted at the
      UFS to help provide a better understanding of risk factors for HIV infection
      among UFS students in comparison with the behaviour patterns of students at other
      universities. Stereotypes identified as known risk factors making students at
      other universities more vulnerable to HIV and high-risk sexual behaviour, were
      also found among UFS students. Results indicated the existence of the following
      statistical significant correlations: African cultural students, gender and their
      viewpoint that there is a stronger relationship between homosexuality and
      HIV/AIDS; their opinion that HIV/AIDS is more strongly associated with African
      students. Data obtained from this survey questionnaire show that even if students
      have a great deal of knowledge to their disposal, and even if they recognised
      that they were personally at risk, some students' sexual practices and risk
      taking behaviour remained unchanged. Despite the fact that the majority of
      students (85%) concluded that it is unacceptable for a woman or a man to have
      more than one sexual partner and that it is better to wait until marriage before
      engaging in a sexual relationship, 17% of male students (Western culture) and 4%
      of female students indicated that they have had more than five sexual partners in
      their lives. Statistical significant correlations also existed between African
      students, gender and their sexual activity the last six months. Contradictory to
      research results reported in literature, data obtained from this survey indicate
      that the majority of students view condom use in a positive light--75% of
      participating African students disagreed with the statement 'not using a condom
      during sexual intercourse shows trust in your partner'. Finally, in an
      interesting revelation, a general sexual culture was identified among UFS
      students, rather than culturally-based sexual practices.

PMID- 19177969
TI  - Health care practices influencing health promotion in urban black women in
      Tshwane.
AB  - Health promotion is a multifaceted activity. Women and children are particularly
      vulnerable regarding access to quality health care, with young African women
      reportedly the poorest and most economically marginalised and least educated
      sector in South Africa. Understanding the context within which a person lives is
      an essential component in the health educator's teaching strategy. Understanding
      urban black women's health care practices will enable health promoters to develop
      interventions that are successful. The problem investigated was to gain an
      understanding of the health care practices of urban black women that could
      influence health promotion activities. The design was qualitative exploratory.
      The respondents were women living in an urban township in Tshwane, South Africa.
      The sampling method was convenient and purposive and the sample size was
      determined by saturation of the data. Data was gathered through semi-structured
      interviews using six specific themes and the analysed using open coding. The
      results indicated that the social environment created by the registered nurses in
      the primary health influenced the health care practices of the women negatively.
      Practices regarding the seriousness of a health problem suggest a possible reason
      for late admission of a person with a serious health problem.

PMID- 19177970
TI  - Expectations of postgraduate nursing students: an inquiry.
AB  - Postgraduate supervision in South Africa currently takes place in the context of
      university transformation with a notable increase in concern for quality. The
      latter is determined by the extent to which students' expectations within a
      supervisory practice are met. This study investigated students' expectations
      regarding their research supervision in a postgraduate nursing programme. A 48
      item questionnaire was mailed to 24 postgraduate students, of which 22 (92%)
      responded, to determine their expectations within a supervisory relationship.
      Items in the questionnaire included students' perceptions of the responsibilities
      of the institution, the department, the supervisor and students' responsibilities
      regarding their supervised postgraduate studies in the School of Nursing Science.
      Descriptive statistics, namely frequencies and percentages for categorical data
      and means and standard deviations or medians and percentiles for continuous data,
      were calculated. Findings indicate that more than 80% of the postgraduate
      students in the study expected the university and the department to provide them
      with structures that would enable them to succeed in their studies. They also
      believed that the student had a major role to play in ensuring that studies were
      completed. Recommendations included making a code of practice for postgraduate
      supervision available to students and the use of a learning contract to clarify
      roles and expectations in the supervisory process. It was also recommended that
      supervisors should be trained to supervise students.

PMID- 19177971
TI  - Humor: a pedagogical tool to promote learning.
AB  - BACKGROUND: It has become critical that learners are exposed to varied methods of
      teaching and assessment that will promote critical thinking of learners. Humor
      creates a relaxed atmosphere where learning can be enhanced and appreciated. When
      learners are relaxed, thinking becomes eminent. Authoritative and tense
      environment hinders thinking. AIM: This paper seeks to explore the perceptions of
      nurse teacher learners regarding the use of humor as a pedagogical tool to
      promote learning. METHOD: A qualitative, exploratory, descriptive and contextual
      research design was employed (Burns & Grove, 2001:61; Mouton, 1996:103). 130
      naive sketches were collected from nurse teacher learners who volunteered to take
      part in the study (Giorgi in_Omery, 1983:52) Follow up interviews were conducted
      to verify the findings. A qualitative, open-coding method of content analysis was
      done Tesch (in Creswell, 1994:155). Measures to ensure trustworthiness of the
      study were taken in accordance with the protocol of (Lincoln & Guba, 1985:290
      326). IMPLICATIONS FOR NURSING EDUCATION, TRAINING AND PRACTICE: The findings of
      the study will assist the nurse educators to create a positive, affective,
      psychological and social learning environment through the use of humor in a
      positive manner. Nurse educators will appreciate the fact that integration of
      humor to the learning content will promote the learners' critical thinking and
      emotional intelligence. Negative humor has a negative impact on learning. Learner
      nurses who become critical thinkers will be able to be analytical and solve
      problems amicably in practice.

PMID- 19177972
TI  - Factors influencing nurses' job satisfaction in selected private hospitals in
      England.
AB  - The quantitative descriptive survey used self-completion questionnaires to study
      factors influencing nurses' job satisfaction in selected private hospitals in
      England. Herzberg's Theory of Motivation was used to contextualise the results
      obtained from 85 completed questionnaires. In terms of Herzberg's Theory of
      Motivation, the most important extrinsic (hygiene) factor was no satisfaction
      with their salaries compared to nurses' salaries in other private hospitals in
      England, in the NHS and even at their own hospitals. However, most nurses were
      satisfied with the other extrinsic factors (organisation and administration
      policies, supervision and interpersonal relations). The most important intrinsic
      factors (motivators), influencing nurses' job satisfaction was their lack of
      satisfaction with promotions (including the fact that their qualifications were
      reportedly not considered for promotions), lack of advancement opportunities and
      being in dead-end jobs, and lack of involvement in decision- and policy-making
      activities. Nurses' levels of job satisfaction might be enhanced if promotion
      policies could be consistent, advancement opportunities implemented,
      qualifications considered for promotions, salary issues clarified, and if nurses
      could be involved in decision- and policy-making. Enhanced levels of job
      satisfaction could help to reduce turnover rates among registered nurses at the
      private hospitals in England that participated in this study.

PMID- 19177973
TI  - Systematic review: predictors of successful transition to community-based care
      for adults with chronic care needs.
AB  - Difficult transition from acute hospital back to the community can be
      challenging. Problems encountered during this process can lead to unplanned
      readmission and emergency department visits. It is important for care managers to
      be able to identify patients susceptible to difficult transition and to
      understand strategies to reduce risk of unplanned hospital readmission. This
      qualitative systematic review of 10 studies of discharge interventions and
      patient characteristics finds little evidence that enhanced discharge support is
      related to improved physical status at home, but there is mixed support for its
      role in preventing or delaying hospital readmissions in certain discharge
      diagnoses, specifically heart failure and stroke. Additionally, those with
      adequate social support and confidence in their self-care ability tend to
      experience fewer readmissions than do those living alone and those who perceive
      themselves as not ready to return home.

PMID- 19177974
TI  - Measuring case managers' advance care planning practice: translating focus group
      findings to survey development.
AB  - Sequential mixed methods is a useful research design to inform second-stage
      methodology when investigating an area of practice in which relatively little is
      known. This article describes how focus group findings were used to measure
      advance care planning practice among community-based case managers. The initial
      qualitative study utilized focus groups to explore aspects of practice in this
      area. Data revealed themes that embodied ambiguous views of advance care
      planning, divergent roles in practice, a continuum of practice activities, and
      multiple facilitators and barriers to practice. In order to further examine case
      managers' advance care planning practices, qualitative findings were used to
      develop the Case Managers Advance Care Planning Practices Instrument.
      Implications for qualitative to quantitative measurement are discussed.

PMID- 19177975
TI  - Geriatric education today: studies from a university hospital.

PMID- 19177976
TI  - Geriatric psychiatry and fellowship programs in the United States.
AB  - Psychiatric disorders are extremely common in the elderly and are a major cause
      of morbidity and mortality. For example, 8% to 15% of the geriatric population
      has clinically significant symptoms of depression (NIH Consensus Conference,
      1992). Elderly Americans commit suicide at a rate twice the national average
      (National Strategy for Suicide Prevention, 2007). Ten to 15% of elderly community
      residents have Alzheimer's disease (AD) or other dementias (Evans et al., 1989).
      AD is the seventh-leading cause of death in the United States (Centers for
      Disease Control 2006).

PMID- 19177977
TI  - Teaching at an assisted living facility.
AB  - The increase in assisted living facilities (ALFs) of various types has provided a
      new option for the delivery of clinical services to the elderly. For all these
      facilities, whether large or small, profit or nonprofit, primarily residential
      (the "social model") or with significant nursing care (the "new" model), their
      sole mission is to provide an appropriate level of residential and clinical
      services to their residents. However, given the rise in the number and variety of
      these facilities, there may be other uses to which they can be put. Specifically,
      these facilities may make excellent sites for the education and training of
      health care personnel. Acute care hospitals and nursing homes primarily deliver
      clinical services, but both are common sites for the training of a variety of
      health care personnel, both professional and nonprofessional. This article
      examines the teaching programs at one ALF and explores some possibilities for the
      future.

PMID- 19177978
TI  - Finding common ground: an integrative model of geriatric medicine and geriatric
      psychiatry fellowship education.

PMID- 19177979
TI  - Swimmies and surfboards.

PMID- 19177980
TI  - Are you strong enough to be a nurse? Using the Nursing Exploration Patch and
      Medicine Merit Badge to spotlight nursing for girls and boys.

PMID- 19177981
TI  - Shifting paradigms of cultural competency.

PMID- 19177982
TI  - Dynamics of diversity: becoming better nurses through diversity awareness.

PMID- 19177983
TI  - Diversity... Fostering a more inclusive and open understanding of difference.

PMID- 19177984
TI  - Transcending differences: a holistic approach.

PMID- 19177985
TI  - Transforming traditions: men shaping a diverse new face of nursing.

PMID- 19177986
TI  - On Oklahoma's mental health...

PMID- 19177987
TI  - Change.

PMID- 19177988
TI  - A unique therapeutic approach to complicated grief.

PMID- 19177989
TI  - Addressing the general medical needs of a patient with an altered mental state.
AB  - Patients presenting to an Emergency Department with an altered mental state,
      whether from a psychiatric, medical or surgical condition or a combination of
      psychiatric and medical or surgical conditions, require more than the usual
      amount of diagnostic acumen. General medical conditions often appear in the guise
      of dysfunctional emotions and/or behaviors. Acute and chronic psychosis may mask
      underlying acute and chronic medical and surgical conditions. As the case of
      Esmin Green of Brooklyn, New York, illustrates, the failure to identify
      underlying medical and surgical conditions in delirious, demented, or psychotic
      patients can prove fatal to the patient and economically costly to the medical
      center and its employees.

PMID- 19177990
TI  - Behavioral health in Oklahoma: making recovery a reality.
AB  - We have come a long way in helping people recover from mental and addictive
      disorders; yet, today, in an era in which medical and technological advancements
      are commonplace, it is surprising how much stigma and misperception still
      surround these illnesses, especially given their prevalence.

PMID- 19177991
TI  - Depression and Oklahoma's poor health status: a connection?
AB  - There is clearly a connection between depression and cardiovascular disease, and
      suicide, obesity, and diabetes. Maternal depression has a considerable impact on
      both the mother and the child. A brief review of scientific findings in this
      regard leads to two conclusions. First, the high incidence of depression in
      Oklahoma contributes to its poor health status. Second, our physicians can make a
      difference by increased attention to the possibility of depression in their
      patients regardless of specialty.

PMID- 19177993
TI  - Media coverage and children's reactions to disaster with implications for primary
      care and public health.
AB  - To address the potential for media coverage of traumatic events to generate fear
      reactions in children, we examined exposure and reactions to media coverage of
      the 1995 Oklahoma City bombing in children attending a middle school 100 miles
      from the disaster site two and three years after the event. Many of the children
      studied recalled feeling "afraid," "sad," or "mad" in relation to initial media
      coverage. Overall exposure and reactions to bomb-related media coverage declined
      over the three years. However, these reactions persisted for some children and,
      when they did, the reactions were related to exposure to coverage right after the
      bombing. Approximately one-fourth of the children recalled that the bombing made
      them feel "a lot" less safe in their home, school, and/or neighborhood. These
      perceptions persisted for approximately 10% of the children. Our Findings suggest
      the importance of primary care and public health interventions to determine and
      monitor children's reactions.

PMID- 19177994
TI  - Physician suicide--a problem for our time.

PMID- 19177992
TI  - Maternal depression after delivery in Oklahoma.
AB  - BACKGROUND: The reduction of depression after delivery is one of the Healthy
      People 2010 targets. Postpartum depression (PPD) can inhibit care-giving
      practices and mother-child bonding and can lead some women to harm themselves.
      This study will examine correlates of maternal depression after delivery and
      associated stressors and will provide recommendations to address this issue in
      Oklahoma. METHODS: Oklahoma Pregnancy Risk Assessment Monitoring System (PRAMS)
      data were used to estimate prevalence among demographic groups and related
      behaviors. Logistic regression modeling was used to produce adjusted odds ratios
      (p < 0.05) for factors and predictors associated with depression after delivery.
      RESULTS: One in four new mothers reported symptoms of maternal depression within
      two to six months postpartum. Women 20-24 were twice as likely to indicate
      symptoms of depression when compared to women 35 or older; adolescents were 2.5
      times as likely. Stressors found to increase the risk of depression symptoms were
      having an unintended pregnancy, arguing with a partner more than usual during
      pregnancy and having bills they could not pay. Receiving a postpartum health
      checkup was protective against postpartum depression symptoms. CONCLUSION: Every
      postpartum woman in Oklahoma should be screened for PPD using a valid and
      reliable scale. Providers should discuss the risks of PPD with pregnant women as
      a routine part of their prenatal care and encourage women to receive their
      postpartum health checkup within six weeks of delivery.

PMID- 19177995
TI  - Reaching toward hope: the state of homelessness and substance use disorders in
      Oklahoma.
AB  - The relationship of homelessness and substance abuse is an important source of
      unmet treatment need and economic loss. Indeed, substance use often precedes
      homelessness and complicates one's return to the community. This paper discusses
      the relationship of homelessness and substance use disorders and identifies this
      population's demographic in Oklahoma. With this foundation, this paper turns to
      the barriers associated with recovery. Also explored is current evidence-based
      research and national strategies for providing treatment and basic needs for this
      population, linking this research to current practices and policies in Oklahoma.
      Concluding discussion identifies qualities of successful treatment programs and
      Oklahoma's efforts to provide effective treatment, which have led to its recent
      award of the Cooperative Agreements for Mental Health Transformation Grants.
      These grants guide Oklahoma into a future marked by recovery and return to the
      community for these suffering individuals.

PMID- 19177996
TI  - Let's talk facts about bipolar disorder (manic depression).

PMID- 19177997
TI  - Let's talk facts about anxiety disorders.

PMID- 19177998
TI  - Let's talk facts about depression.

PMID- 19177999
TI  - Let's talk facts about substance abuse and addiction.

PMID- 19178000
TI  - Let's talk facts about teen suicide.

PMID- 19178001
TI  - Let's talk facts about what is mental illness?

PMID- 19178002
TI  - Elective induction of labor: part 2.
AB  - The elective induction of labor has become commonplace, and many are concerned
      that the practice introduces risks for the woman and the fetus that would not be
      incurred if labor had been allowed to begin spontaneously. This second paper of a
      two-part communication reviews the risks and benefits of the elective induction
      of labor, and concludes that the risks of the induction of labor are few when the
      patient is properly screened medically and appropriately informed. The principal
      worry is a doubled risk of Cesarean delivery among primigravidas (not multiparas)
      in whom labor is electively induced. The benefits of selecting the date of
      delivery are powerful incentives for busy working women. But the benefits are
      primarily social, and add to the convenience of both the patient and her doctor.
      The risks, however, are medical, and are not confined to the pregnancy at risk.
      Appropriately informed consent is the key to balance the risks and benefits.

PMID- 19178003
TI  - Physician's intervention can double smoker's chance of quitting.

PMID- 19178004
TI  - Strategic goals.

PMID- 19178005
TI  - What to expect in 2009 in the NC General Assembly.

PMID- 19178007
TI  - For you and your patients.

PMID- 19178006
TI  - Mary Lewis Wyche.

PMID- 19178008
TI  - More on South Asians and heart disease.

PMID- 19178009
TI  - Why nurse practitioners? Innovative providers lead the charge.

PMID- 19178010
TI  - Serving the uninsured: build relationships to keep costs low.

PMID- 19178011
TI  - Iron deficiency in athletes: women outpace men by a mile.

PMID- 19178012
TI  - Patient information. Psoriasis: how to cope with this lifelong skin condition.

PMID- 19178013
TI  - Backing up your data: planning for failure can limit data loss.

PMID- 19178014
TI  - Fishhook removal: a common cause of soft tissue injuries.

PMID- 19178015
TI  - Patient information. Probiotics: what are they and how might they help me?

PMID- 19178016
TI  - Uterine fibroids: brief overview of presentation, diagnosis and treatment.

PMID- 19178017
TI  - Stuck in between: a closer look at perimenopause.

PMID- 19178018
TI  - Clear and present danger: management of women with LCIS.

PMID- 19178019
TI  - Nutrition and breast cancer: from green tea to grape seed, more study needed.

PMID- 19178020
TI  - Detour around surgery: tuck and tone to treat pelvic organ prolapse.

PMID- 19178021
TI  - Modern-day malaria: an overview of this lingering threat.

PMID- 19178022
TI  - E coli O157:H7 infection: not just a news headline.

PMID- 19178023
TI  - Serotonin syndrome: be aware in primary care.

PMID- 19178024
TI  - Health care reform: NPs can make a difference.

PMID- 19178025
TI  - Thyroid diseases, dyslipidemia and cardiovascular pathology.
AB  - INTRODUCTION: The relationship between thyroid hormones and lipids has long been
      studied, having been first described more than 70 years ago. Since then, much new
      information has been discovered, which justifies a reevaluation of the
      relationship between thyroid pathology and dyslipidemia. Thyroid hormones play an
      important role in regulating lipid metabolism, and thyroid dysfunction can result
      in lipid abnormalities which increase the risk of endothelial dysfunction,
      hypertension and cardiovascular disease. METHODOLOGY: A review of the literature
      was carried out on the association between thyroid diseases, lipid profile and
      cardiovascular risk, using the Medline database and textbooks. Articles in
      English and Portuguese published between 1980 and 2007 were selected. Data
      collection took place between 2003 and 2007. RESULTS: The increased
      cardiovascular risk in thyroid dysfunction is related to lipid profile,
      endothelial dysfunction, metabolic, hormonal and hemodynamic changes and
      coagulation disturbances. Because of its high prevalence in the population
      hypothyroidism is the principal functional disorder. Lipid anomalies associated
      with hypothyroidism are at least partially responsible for the increase in
      coronary heart disease. CONCLUSION: The clinical benefit of treating subclinical
      hyperthyroidism is still the subject of debate, but treatment appears to be
      associated with beneficial effects on lipi d profile and cardiovascular function.
      Further studies are required to clarify the influence of various degrees of
      thyroid dysfunction in the development of atherosclerosis and cardiovascular
      morbidity.

PMID- 19178026
TI  - Impact of isolated bypass grafting of the left internal thoracic artery to the
      left anterior descending coronary artery in high-risk patients with three-vessel
      coronary artery disease.
AB  - INTRODUCTION: Multiple strategies to achieve some degree of myocardial
      revascularization are available. In some, less complete revascularization is
      accepted to limit invasiveness, mostly in older, high-risk patients and patients
      with unsuitable coronary anatomy. METHODS: Patient and operative data were
      collected retrospectively for all patients with three-vessel coronary artery
      disease who had off-pump coronary artery bypass surgery from January 2003 through
      December 2005. In-hospital outcomes, preoperative risk, survival and
      postoperative complications were compared between patients with complete (n = 89)
      and incomplete (n = 61) revascularization. RESULTS: The mean follow-up was 20.2
      +/- 4.6 months. Patients with incomplete revascularization tended to be older
      (76.8 +/- 1.4 years) than those with complete revascularization (66.3 +/- 1.0
      years) and were more likely to have diabetes (43% versus 30%), cerebrovascular
      disease (18% versus 11%) and peripheral arterial disease (20% versus 9%), poorer
      ejection fraction (34.7 +/- 1.7% versus 50.8 +/- 1.5%) and greater EuroSCORE risk
      (9.7 +/- 2.1 vs. 5.1 +/- 1.3). In-hospital (3.3% versus 3.4%) and 6-month (4.9%
      versus 5.6%) mortality were not statistically different in the two groups, nor
      was recurrence of angina (3.3% versus 1.1%) or need for repeat revascularization
      (percutaneous or surgical) (4.9% versus 3.3%). CONCLUSION: In high-risk patients
      with three-vessel coronary artery disease, the potential benefits of less
      invasive surgery should be considered. Surgical outcomes depend on preoperative
      condition rather than incomplete revascularization. Medium-term mortality and
      cardiac-related events associated with this surgical strategy are not increased.

PMID- 19178027
TI  - In-hospital delay in ST-segment-elevation myocardial infarction after Manchester
      Triage.
AB  - INTRODUCTION: In ST-segment elevation myocardial infarction (STEMI), time to
      reperfusion influences morbidity and mortality, and reducing in-hospital delay
      (IHD) continues to be important. Doubts have been expressed whether the
      Manchester Triage System (MTS) contributes to this objective. OBJECTIVE: To
      evaluate the effectiveness of the MTS in classifying STEMI patients and its
      effect on IHD. METHODS: We analyzed 278 patients with STEMI admitted to the
      Coronary Care Unit through the Emergency Department between January 13 2005 and
      November 26 2006. The patients were divided into two groups according to their
      MTS classification: Group A--emergent and very urgent patients; Group B--urgent
      and standard patients. The two groups were compared in terms of clinical and
      demographic characteristics, pre-hospital delay (PHD), IHD and door-to-needle
      (DNT) and door-to-balloon (DBT) times. RESULTS: The mean age of the patients
      studied was 68 +/- 14 years, and 184 patients (65.7%) were male. Group A
      comprised 220 patients (79%) and Group B 58 patients (21%). There were no
      significant differences between the two groups in clinical or demographic
      characteristics or in PHD. IHD, DNT and DBT were significantly longer in Group B.
      CONCLUSIONS: 1) Although the majority of STEMI patients were classified as
      emergent or very urgent, the percentage not classified as such by the MTS was
      excessively high. 2) This could not be explained by clinical characteristics or
      by PHD. 3) The incorrect classification by the MTS of patients with STEMI
      resulted in significantly increased IHD in a large proportion of patients,
      limiting prompt access to reperfusion therapy.

PMID- 19178028
TI  - Echocardiographic assessment of secundum-type atrial septal defects in the adult:
      role in treatment decisions.
AB  - The purpose of this study is to evaluate morphologic patterns of ostium secundum
      type atrial septal defects (osASD) in the adult, analyzing their role in
      treatment decisions. The population was composed of 155 adults (age 43.3 +/- 18.9
      years) consecutively diagnosed with osASD in our center, and confirmed by
      transthoracic and transesophageal echocardiography, between January 2000 and
      December 2007. Of these, 83 (53.5%) underwent successful percutaneous closure.
      Surgical closure was used in 31 patients (20.0%). The remaining 42 patients
      (27.1%) received conservative medical treatment. The mean diameter of the defects
      was 15.8 +/- 8.5 mm. The prevalence of mitral valve prolapse and severe pulmonary
      hypertension was also assessed. Based on the criteria in the literature, we
      detected 14 different morphologic patterns of osASD. There was a central defect
      in 45/155; 40/155 had a short rim and 20/155 two short rims, 24/155 were
      multifenestrated and 15/155 PFO-like, and 12/155 had three or more short rims.
      The different morphologic patterns in each treatment arm, as well as the criteria
      leading to their inclusion in each, are described. While percutaneously closed
      defects had a simpler morphology, those that were surgically closed were normally
      larger and had a more complex shape (with two or more deficient rims or
      multifenestrated, and thus not suitable for percutaneous closure).

PMID- 19178029
TI  - Carvedilol as a protector against the cardiotoxicity induced by anthracyclines
      (doxorubicin).
AB  - The myocardium is a tissue rich in mitochondria, which are of great importance in
      the maintenance of cardiac function. Carvedilol is a non-selective beta-blocker
      which, besides its neuroprotective and vasculoprotective properties, has
      cardioprotective and antioxidant effects. The number of patients undergoing
      chemotherapy is increasing, and doxorubicin is one of the most potent
      antineoplastics. However, its use is frequently associated with cardiotoxicity,
      which results from the interaction between doxorubicin and the reduced form of
      exogenous nicotinamide adenine dinucleotide dehydrogenase (NADH-D), found in
      cardiac mitochondria, resulting in the production of reactive oxygen species
      (ROS). The aim of this review article is to revisit the available evidence on the
      cardioprotection of carvedilol when associated with doxorubicin and to explain
      the mechanisms underlying the benefits of their co-administration.

PMID- 19178030
TI  - The heart in the hands of writers.

PMID- 19178031
TI  - Brucella endocarditis--case report and literature review.
AB  - Endocarditis is a rare and serious complication of brucellosis and is the main
      cause of death in this pathology. Diagnosis requires a high level of suspicion
      and is based on the association of epidemiological, clinical and serological
      elements. Echocardiography plays a crucial role in early diagnosis, as well as in
      identifying predisposing heart disease and local complications typical of this
      pathology. Treatment is not consensual; most authors recommend an early surgical
      approach, due to the degree of tissue destruction caused by Brucella and the high
      rate of recurrence. Nevertheless, other authors stress the need for prognostic
      stratification of each case and support conservative treatment in low-risk cases.
      This article describes the case of a patient with brucella endocarditis that was
      treated medically and reviews the relevant literature.

PMID- 19178032
TI  - Evaluation of a sinus venosus atrial septal defect by magnetic resonance: a case
      report.
AB  - Although superior sinus venosus is one of the major types of atrial septal defect
      (ASD), diagnosis is usually more difficult than the more common forms. We report
      a case in which cardiovascular magnetic resonance (CMR) was useful in evaluating
      a patient presenting with right heart dilatation. Besides establishing the
      diagnosis of atrial septal defect, it also documented the anomalous drainage of a
      pulmonary vein.

PMID- 19178033
TI  - Ebstein's anomaly: a case with an unexpected evolution.
AB  - Ebstein's anomaly of the tricuspid valve is a rare and complex congenital heart
      defect. Its etiology is unknown and in the majority of cases it is
      multifactorial. Mortality in the neonatal period is high. The authors present a
      case of severe Ebstein's anomaly diagnosed antenatally. In the perinatal period a
      Blalock-Taussig shunt was performed and at the age of five months the infant
      underwent successful percutaneous pulmonary valvuloplasty. The clinical outcome
      has been favorable and we decided to postpone a Glenn procedure. At 18 months the
      child is asymptomatic.

PMID- 19178034
TI  - Eustachian valve bacterial endocarditis--a rare location.

PMID- 19178035
TI  - Endomyocardial fibrosis diagnosed by imaging.

PMID- 19178036
TI  - History of cardiology: Eduardo de Arayjo Coelho, MD, PhD. An overlooked European
      pioneer of cardiac research.

PMID- 19178037
TI  - The founder of a key European Association. Fausto Pinto, MD, PhD, FESC, is the
      founder of the European Association of Echocardiography.

PMID- 19178038
TI  - Myotonic dystrophy type 1 requires close cardiologic and neurologic surveillance.

PMID- 19178039
TI  - [Radioecology as a branch of natural science: some thoughts on the interesting
      past, intricate and vital present and future prospects].
AB  - The paper describes more than a century-old history of radioecology, science
      which studies radionuclide migration in the environment and ionizing radiation
      effects on biota. The main stages are identified in the development of this
      branch of natural science associated with the study of problems of radioactive
      contamination of the biosphere (global radionuclide fallout after nuclear weapons
      tests, radiation accidents with the release of radioactive substances to the
      environment). Currently, the basic imperative of radioecological investigations
      is the analysis of radioecological aspects of nuclear power engineering (mainly
      problems of radioactive waste management). Issues are discussed of radiation
      protection of biota (environment)--the anthropocentric (sanitary-hygienic) and
      ecocentric approaches. The importance of radioecology is indicated as the most
      advanced field of ecology in studying anthropogenic effects on the nature.

PMID- 19178040
TI  - [The comparative analysis of 137Cs, 40K, K, 90Sr and Ca allocation in builders of
      an ground part of wood plants in a quasi-equilibrium condition].
AB  - The examinations of allocation of radioactive isotopes of caesium and of
      strontium and of their chemical analogs in a stand of forest ecosystems are
      carried out. By results of examinations and analysis of literary data the
      presence of analogy in allocation of these elements on builders in quasi-balanced
      (concerning radionuclides) state was confirmed. The question about the
      opportunity of use of data about behaviour of K and of Ca is considered at an
      explanation of the mechanisms of redistribution of 137Cs and of 90Sr in wood
      plants and for buildup of mathematical models of behaviour of datas of
      radionuclides in ground ecosystems.

PMID- 19178041
TI  - [Mechanisms of detoxification efficiency of new enterosorbent in combined
      radiation pathology].
AB  - Studies with rats and white mice demonstrated that combined radiation injury
      (CRI) comes to reducing protease activity in small intestine tissues. In liver
      tissue the activity of cathepsine D increased under the action of new
      enterosorbent--clay of Kaluga deposit ("CKD"). In blood serum of the damaged
      animals the amount of histogenic toxins--middle mass molecules (MMM) and
      oligopeptides decreased after "CKD" administration. An effective fixation and
      withdrawal of bacteria from the bowl of the affected animals took place. The
      survival level of mice in 30 days after CRI comprised 20% as compared with 60% in
      the case of "CK D" administration. It is supposed that the increase of survival
      after "CKD" administration is the result of enhancement of macrophage
      detoxification in liver, determined on the increase of activity of cathepsine D
      (lysosomal protease), elimination of MMM and normalization of gut microflora.

PMID- 19178042
TI  - [Immunomodulation effects volatile secretion of animals at postradiation
      immunodeficiency conditions].
AB  - Was shown, that given off with urine the volatile chemosignals of intact and
      irradiated (4 Gy) mice and rats restored the ability to humoral immune response
      and other parameters immunity lowered by ionizing radiation in the dose 1 Gy. The
      chemosignals off intact individuals have shown higher immunerestoring activity in
      comparison with the irradiated ones. As opposed to post-radiation signals they
      activated in the major degree at irradiational mice phagocytic activity
      peritoneal macrophages and also the number in the blood at rates not only
      erythrocytes but lymphocytes and granulocytes. It is supposed, that mammals
      possess the distant immunomodulating chemosignal system, direct on
      immunoreactivity of individuals with immunodeficiency of state.

PMID- 19178043
TI  - [Dynamics of the rats higher nervous activity disturbances after partial
      influence of high energy electrons in high doses].
AB  - The dynamics of the disturbances of stabilized motor defensive conditioned reflex
      of active avoidance in "shuttle-box" in rats after total and partial (the head or
      body irradiated) influence of high energy electrons in dose 100 Gy was
      investigated. The head irradiation, the same way as total irradiation, provoked
      the early effects of disturbances of higher nervous activity, specifically,
      initial shock-like effect--the "early transient incapacitation" (ETI). The head
      shielding, on the contrary, prevents these disturbances. At the same times the
      body irradiation in dose 10 Gy (this dose don't provoke ETI effect) provoked
      practically the same disturbances of higher nervous activity as the total
      irradiation. Consequently, in animals irradiated in super-lethal doses the early
      disturbances of higher nervous activity provoked of direct influence of ionizing
      radiation to the brain. In animals irradiated in lesser doses these disturbances
      caused of non direct effects basically.

PMID- 19178044
TI  - [The dynamics of survival rate of experimental polulations of Drosophila
      melanogaster undergone to a chronic irradiation].
AB  - In genetically non-uniform populations Drosophila melanogaster in conditions of a
      chronic irradiation in a doze 10-11 sGy/generation dynamics parameters of
      populations was investigated. It is established, that number of individuals in
      irradiated populations is lower, than in control. It is revealed, that viability
      of populations undergone to a chronic irradiation depends on their genotype. The
      gradual increase in fruitfulness, viability of individuals and the decrease in a
      level of lethal mutations in a number of generations after an irradiation in
      small dozes is caused by adaptable opportunities of the populations.

PMID- 19178045
TI  - [The analysis of genomic mutations and structural chromosome aberrations in
      irradiated human lymphocytes].
AB  - The lymphocytes of healthy donors were exposed to 60Co gamma-rays in doses
      ranging 0.5 to 6.0 Gy, and were incubated with PHA and 5-bromodeoxyuridine at 37
      degrees C for 72 h. In the course of five consecutive in vitro divisions of
      cultured lymphocytes, the frequency of polyploid metaphases were determined, and
      chromosome structural aberrations in polyploid and diploid metaphases were
      analyzed. Dose dependence of polyploid formation was investigated, and patterns
      of polyploid cells were analyzed at various DNA replication cycles post exposure
      and 5-bromodeoxyuridine addition. Radiation is most effective induces of
      polyploid metaphase of the second and of the third mitotic divisions. In
      metaphases of the fourth mitotic divisions radiation does not enlarge
      authentically frequency of polyploid cells. In metaphases of the fifth divisions
      was not retrieved of polyploid cells. Was shown, that 84.8% of polyploid
      metaphases compound of tetraploids, while of octoploids and the cells with
      endoreduplicated chromosomes compound, accordingly, 8.4 and 6.8%. The analysis of
      chromosome aberrations have shown that the percentage of aberrant cells was
      higher in polyploid metaphases than in diploids, which indicated that chromosome
      lesions were involved in formation of polyploid metaphases.

PMID- 19178046
TI  - [The analysis of mutations at mini- and microsatellite DNA loci in the family
      members of a group of occupationally exposed to tritium and tritium oxide plant
      workers].
AB  - Mini/microsatellite (MNS/MCS) loci are efficient tools in solving basic and
      applied problems in different spheres of biology and medicine due to their unique
      characteristics - a high frequency of tandem repeats in combination with their
      wide variability. Specifically, they have been found use as potential markers of
      genetic effects of ionizing radiation on animals and on human. However there is
      no general agreement as to the influence of irradiation on the frequency of
      mutations in hypervariable repetitive DNA sequences up to now. The present work
      is the study of the mutation frequency at MCS/MNS loci in 19 families of workers
      occupationally exposed to chronic beta-radiation from tritium and tritium oxide
      (examined group), and in the control group included 23 families. The results have
      indicated that the average frequency of microsatellite mutations in the examined
      group made up 4.7% and exceeds about 7-fold the same parameter of the control
      group (0.7%). This differences is statistically significant (p = 0.004). The
      average frequency of minisatellite mutation in the examined group made up 3%
      while in the control group it was 2 time lower (1.5%), but this difference is not
      statistically significant. Mutations for 4 MCS and 2 MNS loci were revealed in
      two children from one family (the total reconstructed dose in their father was
      about 1000 mSv). If we exclude this family from statistical analysis the
      frequencies of MCS and MNS mutations in the children of nuclear workers do not
      statistically differ from the control values.

PMID- 19178047
TI  - [Retina radioresistance: whole-body exposure of mice to gamma-irradiation induces
      the retina DNA damage, accumulation of p53 protein followed by DNA repair rather
      than the apoptosis].
AB  - Whole-body irradiation of mice with gamma-rays at 14 Gy causes DNA single and
      double strand breaks effectively repaired later. p53 is accumulated during the
      repair period. There is still some amount of DNA breaks 48-72 hours after the
      irradiation. Despite p53 accumulation and residual DNA lesions in the cells, mice
      retina demonstrated no morphological destructive changes or apoptosis signs.
      Retina resistance to apoptotic signals could derive from efficient repair of
      radiation-induced lesions in transcriptionally active regions of the genome of
      differentiated cells.

PMID- 19178048
TI  - [Regulatory radiation risks' for the population and natural objects within the
      Semipalatinsk Test Site].
AB  - Advisability of using risks as indicators for estimating radiation impacts on
      environmental objects and humans has been jusified. Results are presented from
      identification of dose burdens distribution to various cohorts of the population
      living within the Semipalatinsk Test Site (STS) and consuming contaminated farm
      products. Parameters of dose burden distributions are estimated for areas of
      livestock grazing and the most contaminated sectors within these areas. Dose
      distributions to meadow plants for the above areas have been found. Regulatory
      radiation risks for the STS population and meadow ecosystem components have been
      calculated. Based on the parameters estimated, levels of radiation exposure of
      the population and herbaceous plants have been compared.

PMID- 19178049
TI  - [The radiosensitivity change of human blood lymphocytes in different mitotic
      cycles after a low dose irradiation].
AB  - The adaptive response (AR) in stimulated blood lymphocytes (8 donors) have been
      studied by two methods: analyses of unstable chromosome aberrations in metaphases
      and micronuclei assay (MN) with cytochalasine cytokinetic block. The adaptive
      irradiation in the dose of 5 cGy have been conducted 24 h and challenge
      irradiation after 48 h after stimulation. For the metaphase analysis of the first
      and subsequent mitosis cells were incubated with BrdU and were fixed 50, 72 and
      96 h after the stimulation. In the MN test cells were fixed 72 or 96 h after the
      stimulation and cytochalasin B was added in the cell culture 24 h before
      fixation. Was shown that in the cells of first mitoses fixed at 50 h after
      stimulation only chromatid aberrations are presented in the lymphocytes of all
      donors and AR in all donors was noticed; but when fixation was conducted 72 h
      after stimulation the chromosome type aberrations are prevailing and AR is
      absent, 96 h after--one donor has AR. Was discovered that in the cells of the
      second mitosis fixed at 72 h after stimulation the only chromosome type
      aberrations observed, their frequency is higher that in the lymphocytes of 1 and
      3 mitosis in the same fixation time, in 7 of 8 donors there is AR registered. In
      the cells of 3th mitosis 72 h fixation time only 1 donor has AR, in cells of the
      4th mitosis nobody have AR. By the MN assay AR in two donors is observed, in the
      first--the increase in radiosensitivity after adapting irradiation is noticed in
      the rest of the radiosensitivity is not changed. 78 percent of results
      coincidence by MN assay with time fixation 72 and 96 h with the results of
      metaphase analysis in the cells of first mitosis in the same time fixation was
      observed. The proposition of these data explanation is that the decrease of
      chromatid and chromosome aberration frequency is the one is result of different
      enzyme systems function and the ability to the these system induction in
      different cells is different. If the one is decreasing the chromatid aberrations
      frequency is induced in lymphocytes of most donors, the second is induced rarely
      only in the part of cells.

PMID- 19178050
TI  - [Survival/death modifiers of intestine epithelium stem cells and thanatological
      mechanisms].
AB  - Till now the thanatological mechanisms that regulated the proliferation and the
      clearance of the stem cells (SC) in fast renewal systems of organism--intestinal
      epithelium remain insufficiently investigated as in haematopoietic system too.
      The relevance of such researches is supported by an essential role of these
      mechanisms in pathogenesis of widely widespread inflammatory and
      hyperproliferative diseases. In particular inhibition/disregulation of
      elimination for the "undesirable", mutant cells leaving from under immune and own
      control is one of the reasons for neoplastic cell expansion. In this review were
      summarized data about some mechanisms determining SC-destruction in animals
      treated by ionizing radiation or antineoplastic preparations, and also treated by
      modifiers of SC-radiosensitivity.

PMID- 19178051
TI  - [The characteristic of radioprotective properties of a radioprotectant B-190 at
      its administration after radiation].
AB  - In experiences on mice F1 (CBAxC57B 1/6) at a gamma-irradiation in a lethal dose
      LD(35-70/30) the radioprotectant B-190 at administration after an exposure would
      rise an animal survival--on 35-55%, caused the increase of the amount of
      endogenic colony in a spleen and of leucocytes in blood on 11th and 30th day of
      an acute radiation desease accordingly. The drug has the effect in the interval
      of doses from 75 up to 150 mg/kg b.w. with the rise of radioprotective action on
      dose reduction factor from 1.1 up to 1.22. alpha(1)-adrenoblockers terasosin in a
      dose of 15 mg/kg b.w. partially would reduce radioprotective properties of B-190
      as radioprotectant or and drug of early therapy of acute radiation desease.

PMID- 19178052
TI  - [Structural and functional changes of human hemoglobin molecules induced by the
      vacuum UV-radiation].
AB  - Structural and functional modifications of human hemoglobin molecules under the
      action of vacuum UV-irradiation of doses 0.6-600 kJ/m2 were studied by means of
      spectrophotometrical method. Structural changes of hemoglobin's molecules after
      irradiation by quantums of the different energy testify the predominance of
      photoionisation processes in the investigated system.

PMID- 19178053
TI  - [Structurally functional modifications of the human lymphocytes induced by
      influence of UV-light].
AB  - The influence of UV-light (240-390 nm) in dose 75.5-1510 J/m2 on the structural
      functional qualities (cytotoxic activity, antibody-produced ability, a level of
      expression of superficial receptors, a level cAMP) of lymphocytes peripheral
      blood of donors was investigated. Corregative action of UV-radiation on cytotoxic
      activity of lymphocytes in relation to cells of Ehrlich ascite carcinoma was
      revealed. The interrelation of modification types of plasmatic membrane
      components with a level of functional activity of lymphocytes was established.
      Was shown, that UV-light induces the decrease in a secondary level of messenger
      cAMP in cytosol of the photomodified cells. It is revealed, that UV-radiation
      causes stimulation of antibody-independent mechanism of cytotoxic lymphocytes,
      which is connected with activation of T-cells and with inhibition of antibody
      dependent mechanism of cytotoxic activity.

PMID- 19178054
TI  - [The 56th session of Science Committee UN(O) about the influence of nuclear
      radiostation].

PMID- 19178055
TI  - [Russian science conference "Medical-Biological Problems of Toxicology and of
      Radiology" (29-30 May 2008, St. Petersburg)].

PMID- 19178057
TI  - Responses to AFP journal club on hip fracture and PPI use.

PMID- 19178058
TI  - Severe occupational lung disease from exposure to flavoring chemicals.

PMID- 19178059
TI  - Having a usual source of care reduces ED visits.
AB  - The recent growth in the use of emergency departments (EDs) is costly,
      undesirable, and unnecessary. This trend is partly due to a growing proportion of
      persons who lack a usual source of care. This group is increasingly likely to
      rely on EDs for their health care needs compared with those who have a usual
      source of care.

PMID- 19178060
TI  - Screening for carotid artery stenosis.

PMID- 19178061
TI  - Common pigmentation disorders.
AB  - Common causes of hyperpigmentation include postinflammatory hyperpigmentation,
      melasma, solar lentigines, ephelides (freckles), and cafe-au-lait macules.
      Although most hyperpigmented lesions are benign and the diagnosis is
      straightforward, it is important to exclude melanoma and its precursors and to
      identify skin manifestations of systemic disease. Treatment options for
      postinflammatory hyperpigmentation, melasma, solar lentigines, and ephelides
      include the use of topical agents, chemical peels, cryotherapy, or laser therapy.
      Caf&-au-lait macules are amenable to surgical excision or laser treatment.
      Disorders of hypopigmentation may also pose diagnostic challenges, although those
      associated with health risks are uncommon and are usually congenital (e.g.,
      albinism, piebaldism, tuberous sclerosis, hypomelanosis of Ito). Acquired
      disorders may include vitiligo, pityriasis alba, tinea versicolor, and
      postinflammatory hypopigmentation. Treatment of patients with widespread or
      generalized vitiligo may include cosmetic coverage, psoralen ultraviolet A-range
      therapy (with or without psoralens), or narrow-band ultraviolet-B therapy;
      whereas those with stable, limited disease may be candidates for surgical
      grafting techniques. Patients with extensive disease may be candidates for
      depigmentation therapy. Other acquired disorders may improve or resolve with
      treatment of the underlying condition.

PMID- 19178062
TI  - Fetal chromosomal abnormalities: antenatal screening and diagnosis.
AB  - Pregnant women of all ages should be offered screening and invasive diagnostic
      testing for chromosomal abnormalities before 20 weeks' gestation. New
      developments in screening methods have increased the number of options for
      patients. Diagnostic options include chorionic villus sampling in the first
      trimester and amniocentesis in the second trimester. Screening options in the
      first trimester include nuchal translucency testing in combination with
      measurement of pregnancy-associated plasma protein A and human chorionic
      gonadotropin. Nuchal translucency testing alone is not as effective. Screening
      options in the second trimester include serum screening using triple or quadruple
      screening, and ultrasonography. Patients may also choose a combination of first-
      and second-trimester screening in an integrated, stepwise sequential, or
      contingent sequential fashion. These options include an analysis of pregnancy
      associated plasma protein A, with or without nuchal translucency testing, in
      combination with quadruple screening. An integrated test with nuchal translucency
      testing is the most effective method for women who present in the first
      trimester. If nuchal translucency testing is unavailable, the maternal serum
      integrated test is safest and most effective. For women who do not present until
      the second trimester, the quadruple screen is recommended. Comprehensive
      counseling should be available to all pregnant women. Specific screening tests
      will depend on availability of the procedure and patient preference.

PMID- 19178063
TI  - Information from your family doctor. Prenatal genetic screening tests.

PMID- 19178064
TI  - Nonpharmacologic management of chronic insomnia.
AB  - Chronic insomnia is highly prevalent in our society, with an incidence of 10 to
      30 percent. It is a major cost to society in terms of health care expenditure and
      reduced productivity. Nonpharmacologic interventions have been studied and shown
      to produce reliable and sustained improvements in sleep patterns of patients with
      insomnia. Cognitive behavior therapy for insomnia has multiple components,
      including cognitive psychotherapy, sleep hygiene, stimulus control, sleep
      restriction, paradoxical intention, and relaxation therapy. Cognitive
      psychotherapy involves identifying a patient's dysfunctional beliefs about sleep,
      challenging their validity, and replacing them with more adaptive substitutes.
      Sleep hygiene education teaches patients about good sleep habits. Stimulus
      control therapy helps patients to associate the bedroom with sleep and sex only,
      and not other wakeful activities. Sleep restriction therapy consists of limiting
      time in bed to maximize sleep efficiency. Paradoxical intention seeks to remove
      the fear of sleep by advising the patient to remain awake. Relaxation therapies
      are techniques taught to patients to reduce high levels of arousal that interfere
      with sleep. Cognitive behavior therapy involves four to eight weekly sessions of
      60 to 90 minutes each, and should be used more frequently as initial therapy for
      chronic insomnia.

PMID- 19178065
TI  - Information from your family doctor. Help with chronic insomnia.

PMID- 19178066
TI  - Choosing topical corticosteroids.
AB  - Topical corticosteroids are one of the oldest and most useful treatments for
      dermatologic conditions. There are many topical steroids available, and they
      differ in potency and formulation. Successful treatment depends on an accurate
      diagnosis and consideration of the steroid's delivery vehicle, potency, frequency
      of application, duration of treatment, and side effects. Although use of topical
      steroids is common, evidence of effectiveness exists only for select conditions,
      such as psoriasis, vitiligo, eczema, atopic dermatitis, phimosis, acute radiation
      dermatitis, and lichen sclerosus. Evidence is limited for use in melasma, chronic
      idiopathic urticaria, and alopecia areata.

PMID- 19178067
TI  - [Model of the interreceptor cluster interaction as the basis for increased neuron
      sensitivity to a mediator].
AB  - Inter receptor relations may result in activation of the majority of cluster
      receptors, when the mediatory concentration is small then to activate "unclucter"
      receptors. The neuron activation by the small mediatory concentration, the
      postsynaptic membrane changes under synaptic modification, the one receptor
      activation by unconnected with him receptor can be explain as results of the
      cluster receptor influence.

PMID- 19178068
TI  - [Physiological role of angiotensin II and IV as active components of the renin
      angiotensin system].
AB  - A review. Modern concepts of the physiological role of basic active component of
      renin-angiotensin system angiotensin II and its 3-8 fragment angiotensin IV are
      stated. The basic ways of formation and further degradation of angiotensin II and
      IV in a body are described. General characteristic of physiological activity and
      possible mechanisms of action of angiotensin II and IV are presented.
      Specifically, the role of angiotensin II and IV in regulation of defensive and
      drinking behaviors of animals is considered.

PMID- 19178069
TI  - [Computing function and its representation in the parietal cortex in humans and
      animals].
AB  - The currently available evidence suggests that not only adults but children of
      preverbal age and animals possess the ability to define numbers. The behavioral
      studies in infants and animals show that number perception, quantity
      discrimination, and elementary adding and subtraction appear in onto- and
      phylogenesis prior to language. There are parallels between number processing in
      animals and humans: a) the ability to discriminate between two numbers improves
      as the numerical distance between them increases; b) for equal numerical
      distance, discrimination of two numbers worsens as their numerical size
      increases. Disorders of "number sense" in brain-lesioned patients and brain
      imaging of number processing in healthy subjects showed that the parietal cortex
      includes the key structures involved in number perception. These structures
      include the intraparietal sulcus area, angular gyrus and superior lobule. Animal
      experiments showed that the parietal cortex is also important for "counting
      behavior" in monkeys (area of the intraparietal sulcus and area 5), dogs (area 5)
      and cats (area 7). Parallels between functional and morphological bases of number
      perception in humans and animals suggest that they endow it in evolution as the
      usual fundamental mechanism of adaptive behavior.

PMID- 19178070
TI  - [Alpha- and theta-bands spatial synchronization in unconscious visual set formed
      for perception of emotional facial expression].
AB  - EEG coherence in the alpha and theta bands during set formation and testing was
      studied in healthy adult subjects (n = 35). The set was formed to pictures of
      faces with a negative emotional expression (an angry face). Different patterns of
      the EEG spatial synchronization were revealed for the theta and alpha bands,
      especially, in subjects who formed the rigid set (erroneous perception of the
      facial expression in the form of contrast and assimilative illusions). An
      increase in coherence in the theta band was observed in subjects of this group (n
      = 23) between the dorsolateral frontal and temporal regions of the right
      hemisphere. A neural mechanism underlying the visual illusions was suggested.
      Analysis of the EEG coherence in the theta and alpha bands makes it possible to
      obtain the "windows" for the insight into operation of the cortico-hippocampal
      and fronto-thalamic functional systems of the integrative brain activity and
      involvement of these systems in perception of facial expression. The fronto
      thalamic system is involved in a more generalized activation of the brain cortex,
      especially of its frontal regions. The theta rhythm system seems to facilitate
      the integration of the frontal and temporal cortices of the right hemisphere and
      association of the right temporal region with the parietal and central regions of
      both hemispheres.

PMID- 19178071
TI  - [Visual evoked potentials in rabbit's visual cortex reflect variations in
      orientation and intensity of lines].
AB  - Amplitude variations of visual evoked potentials (VEP) in rabbit were studied
      using changes of three types of stimuli: lines with different orientations (0-90
      degree) but constant in intensity, lines with different intensities but constant
      in orientation, and complex stimuli with different intensities and different
      orientations. Factor analysis of component N85 of VEP to stimuli with varying
      orientation and constant intensity revealed two-dimensional sensorial space of
      orientations. Also, the two-dimensional achromatic sensorial space was revealed
      for stimuli different only in intensities. In experiments with complex stimuli,
      two versions of stimulation were used. In the first version, four stimuli with
      varying orientation from 0 to 38.58 degrees were of 5 cd/m2 in intensity, the
      remaining four stimuli (from 51.44 to 90 degrees) were of 15 cd/m2 in intensity.
      In the sensorial space, stimuli with different intensities were disposed on the
      plane formed by the first two significant factors in the opposite quadrants,
      whereas within each quadrant, stimuli were arranged according to their
      orientation from minimum to maximum degrees. It is suggested that, in this
      version of stimulation, the interaction between two characteristics (intensity
      and orientation) took place with clear-cut dominance of the factor of intensity.
      In the second version of the experiments, also eight complex stimuli were used.
      Each stimulus was characterized by specific combination of orientation (one of
      the eight directions in the range from 0 to 90 degrees) and intensity (one of the
      eight intensities in the range from 5 to 21 cd/m2). Three or four significant
      factors were revealed in each test. Only the plane of intensity of sensorial
      space (XIX2) formed by two significant factors was revealed in the overwhelming
      majority of cases. On this plane, stimuli were arranged according to their
      intensities. This fact can be explained by specific (twilight) type of rabbit's
      vision with predominant discrimination of intensities. However, some findings
      suggest that visual evoked potentials reflect simultaneous processing of two
      characteristics of visual stimuli (intensity and orientation) being indicative of
      a possibility of the complex stimuli analysis in the primary visual cortex.

PMID- 19178072
TI  - [Selective disruption of memory consolidation in chicks produced by 5'-iodo-2'
      deoxyuridine].
AB  - We tested the hypothesis that DNA synthesis is involved in molecular mechanisms
      of memory consolidation. Nucleotide analogs 5'-iodo- and 5'-bromo-2'-deoxyuridine
      impair DNA functions being incorporated into elongated DNA chain and cause
      amnesia in a number of training models in mice. We studied possible amnestic
      effects of 5'-iodo-2'-deoxyuridine (IdU) in different training models in newborn
      chicks--in passive avoidance, taste aversion, imprinting and spatial learning in
      a maze. In the taste aversion model injection of IdU (10 mg/kg 5 min before or 50
      min after training) produced amnesia at test 1-2 days after training, at the same
      time it had no effect on memory retention in test 6 h after training. IdU
      injection 2 h after training produced no amnesia. Similar amnestic effect in
      taste aversion model was found for 5'-bromo-2'-deoxyuridine (BrdU). In models of
      imprinting, passive avoidance and spatial learning IdU injection before or after
      training had no effect on memory retention. These data presuppose that brain DNA
      synthesis might play a critical role in mechanisms of memory consolidation in
      taste aversion learning in chicks.

PMID- 19178073
TI  - [Features of performance of acquired motor skill in rats with various motor
      preference].
AB  - In Wistar rats with different motor preference (right and left-handed), features
      of performing food-getting skill (extraction of food spheres from a narrow
      horizontal tube-feeder) were examined. When using preferred forepaw, left-handed
      rats performed the task more quickly (including both preliminary attempts and
      final successful movement) than the right-handed ones. This skill was more
      quickly performed with the left paw irrespective of whether this paw was
      preferred or not. At the final stage of skill performance (grasping and
      extraction of food), the preferred paw appeared to be more successful than the
      not preferred one for both the right- and left-handed rats. These results suggest
      that the organization of general strategy of performance of the complex
      behavioral task is determined by functional heterogeneity of the right and left
      hemispheres of the rat brain, and this heterogeneity is not connected with paw
      preference. Specific motor and precision abilities of a preferred paw underlie
      the chosen preference. A special role in realization of these abilities is played
      by a contralateral hemisphere.

PMID- 19178074
TI  - [Specificity of ontogenic development of behavior of rats subjected to prenatal
      hypoxia on the 14-th or 18-th days of embryogenesis].
AB  - Physiological development, movement activity and cognitive functions of rats
      subjected to acute normobaric hypoxia (7% O2 during 3 h) at different days of
      embryogenesis (E14 or E18) were investigated. It was found that prenatal hypoxia
      led to a delay in physiological development and formation of motor behavior
      during the 1st month after birth. Differences observed were more pronounced in
      rats subjected to hypoxia on the 14th day of intrauterine development but
      disappeared with maturation of the animals. Independently of the day of the
      hypoxic episode (E14 or E18), learning ability and memory (long-term and short
      term) impaired in all adult rats. The findings suggest that the exposure to
      hypoxia at the stage of predominant generation and migration of neuroblasts (E14)
      is disruptive for physiological development, formation of motor behavior and
      cognitive function, whereas the exposure to hypoxia at the stage of predominant
      cell maturation (E18) is in general more disruptive for cognitive functions.

PMID- 19178075
TI  - [Depressive-like state and sleep in laboratory mice].
AB  - In order to induce the state of anhedonia, a key symptom of depression, mice were
      subjected to a one-month stress procedure comprised of various stressors.
      Anhedonic state was defined by a reduction of preference for sucrose solution
      over tap water. Conventional cortical and neck-muscle electrodes were implanted
      to control and stressed animals under chloral-hydrate anesthesia. After a two
      week recovery and habituation period, mice from chronically stressed group were
      re-subjected to five-day stress, and the anhedonic state was verified. As not all
      the stressed mice displayed a decrease in sucrose preference, animals were
      divided in two groups: stressed-non-anhedonic and stressed-anhedonic animals.
      Seven-day continuous polygraphic recording was carried out in animals from both
      stressed groups and the control group in recording chambers under conditions of
      12/12-hour light/dark schedule. The anhedonic mice demonstrated a significant
      advanced shift in circadian distribution of paradoxical sleep and increased
      amount of paradoxical sleep during the light period. In the course of the dark
      period, the anhedonic group showed a slight but significant decrease in total
      amount of slow-wave sleep as compared to the non-anhedonic and control groups.
      The results suggest that the changes in sleep structure documented in the model
      of anhedonia are similar to those described for human depression.

PMID- 19178076
TI  - [The model of attention dynamics in perception].
AB  - A new model of perception of an elementary external stimulus is proposed on the
      basis of attention dynamics of a subject of perception. A local quantitative
      measure of attention is introduced with regard to connection of attention with
      analyzer excitability. The solution of the model is compared to the dynamics of
      distribution of the visual analyzer excitability in the process of perception
      measured experimentally. A formula of time dependence of attention on the evoked
      potential amplitude is presented. The theoretical amplitude dynamics is compared
      to the experimental results. The example of reconstruction of evoked potential on
      the basis of the model is given. Pieron's law is deduced in the framework of the
      model. The theoretical relationship between the reaction and stimulus intensity
      corresponds to the Stivens's law.

PMID- 19178077
TI  - [General functional state (tonus) of the brain and conditioned reflexes as the
      mechanisms of it's regulation].
AB  - The article is dedicated to P.S. Kupalov, due to his 120 Anniversary. P.S.
      Kupalov was the disciple of I.P. Pavlov and his nearest collaborator. Right after
      I.P. Pavlov, he was at the head of the Institute of Experimental Medicine in St
      Petersburg, where he developed a number of new ideas, concerning conditioned
      reflexes. Thus, he discovered shortened conditioned reflexes--central mechanisms
      of regulation of general functional state of the brain, and he created, on the
      base of the studies of unlimited motor activity in animals using his own method
      of situational conditioned reflexes, the conception of situational conditioned
      reflexes. P.S. Kupalov found out a number of new explanations for development of
      experimental neuroses and determined their mechanisms, as well. He was the one
      among the first disciples of I.P. Pavlov, who indicated at the complex structural
      functional organization of conditioned reflexes, and he played the great part for
      the creation of modern theory about the nature of behavior, based on conditioned
      reflexes. The most important theses of P.S. Kupalov's conception, which is of
      great cognitive significance at the moment, as well as some results of the
      studies by his disciples and followers, developing the ideas of P.S. Kupalov, are
      presented in the article.

PMID- 19178078
TI  - [OCT4 and NANOG are the key genes in the system of pluripotency maintenance in
      mammalian cells].
AB  - Embryonic stem cells are able to give rise after differentiation to derivatives
      of three germinal layers (ectoderm, endoderm, and mesoderm) and to functional
      gametes. This property of cells is referred to as pluripotency. The pluripotent
      status of preimplantation embryo cells and embryonic stem cells is maintained by
      a complicated system of molecular signaling pathways and transcription factors.
      The key regulators in this system are the transcription factors OCT4 and NANOG.
      The role and place of these factors in the pluripotency-sustaining system and
      their interaction with other factors are considered in the review. Data are
      presented on the structure, chromosomal location, expression, and regulation of
      the Oct4 and Nanog genes in mammals.

PMID- 19178079
TI  - [Epimutations of the KCNQ1OT1 imprinting center of chromosome 11 in early human
      embryo lethality].
AB  - Disturbance of the epigenetic status of the H19 and KCNQ1OT1 imprinting centers
      of chromosome 11 and the CDKN1C imprinted gene in early human embryolethality
      have been studied. This is the first study to detect hypomethylation of KCNQ1OT1
      in the maternal homolog in placental tissues from some (9.5%) spontaneous
      abortions with impaired cell proliferation during the first trimester of
      pregnancy. Tissue specificity of the aberrant methylation status of the
      imprinting center has been found. A hypothesis on the postimplantation origin of
      epimutations in somatic cells of the developing embryo is put forward. The
      selective role of epimutations of imprinted genes in early human ontogeny as
      compared to uniparental chromosome inheritance is considered; estimation of the
      epigenetic risk entailed in using assisted reproductive technologies is
      discussed.

PMID- 19178081
TI  - [Speciation and chromosomal evolution of the Baikalian endemic chironomids of the
      genus Sergentia Kief. (Diptera, Chironomidae): karyotype divergence and
      chromosomal polymorphism in the populations of deep-water species Sergentia
      nebulosa Linevitsh et al. and Sergentia assimilis Proviz V. et Proviz L].
AB  - Specific karyotype structure and chromosomal polymorphism was investigated in the
      populations of Sergentia nebulosa Linevitsh et al., 1984 and Sergentia assimilis
      Proviz V. et Proviz L., 1999, the deep-water endemic chironomid species from the
      Baikal Lake. The distinguishing feature of the karyotypes of these species,
      compared to the other Baikalian Sergentia, is well-developed nucleolus in region
      6 of arm C. Both species display the presence of interspecific population
      polymorphism, determined by the structure of this arm. In some populations,
      chromosome regions from 4 to 6 contain a homozygous inversion, which is absent in
      the other populations. The distinguishing karyotype feature of S. assimilis,
      which shares fluctuating homozygous inversions with the other species, is the
      presence of two species-specific homozygous inversions. These are the secondary
      overlapping inversion in arm A, regions 2 to 7, and the inversion in regions 4 to
      10 of arm G. Both species of interest contain nucleolus organizer in region 10 of
      arm G. In populations of S. nebulosa, six heterozygous inversions localized in
      arms A, B, C, F, and G were discovered. The highest number of heterozygotes for
      inversions (71%) was observed in the population from Southern Baikal. In arm B of
      S. assimilis, one heterozygous inversion and heterozygosity for nucleolus
      organizer in the chromosome region 16 was detected. Chromosomal evolution of
      Baikalian Sergentia, and the role of inversion polymorphism in the population
      adaptation is discussed.

PMID- 19178080
TI  - [Quorum sensing systems of regulation, synthesis of phenazine antibiotics, and
      antifungal (corrected) activity in rhizospheric bacterium Pseudomonas
      chlororaphis 449].
AB  - Strain Pseudomonas chlororaphis 449, an antagonist of a broad spectrum of
      phytopathogenic microorganisms isolated from the maize rhizosphere, was shown to
      produce three phenazine antibiotics: phenazine-1-carboxylic acid (PCA), 2
      hydroxylphenazine-1-carboxylic acid (2-OH-PCA), and 2-hydroxylphenazine (2-OH
      PHZ). Two Quorum Sensing (QS) systems of regulation were identified: PhzIR and
      CsaI/R. Genes phzI and csaI were cloned and sequenced. Cells of strain 449
      synthesize at least three types of AHL: N-butanoyl-L-homoserine lactone (C4-AHL),
      N-hexanoyl-L-homoserine lactone (C6-AHL), and N-(3-oxo-hexanoyl)-L-homoserine
      lactone (30C6-AHL). Transposon mutagenesis was used to generate mutants of strain
      449 deficient in synthesis of phenazines, which carried inactivated phzA and phzB
      genes of the phenazine operon and gene phzO. Mutations phzA- and phzB-caused a
      drastic reduction in the antagonistic activity of bacteria toward phytopathogenic
      fungi. Both mutants lost the ability to protect cucumber and leguminous plants
      against phytopathogenic fungi Rhizoctonia solani and Sclerotinia sclerotiorum.
      These results suggest a significant role of phenazines in the antagonistic
      activity of P. chlororaphis 449.

PMID- 19178082
TI  - [Subcellular localization of isozymes of NAD-dependent malate dehydrogenase in
      sugar beet Beta vulgaris L].
AB  - Subcellular localization of isozymes of NAD-dependent malate dehydrogenase (MDH)
      in sugar beet was studied. Isozymes ss and 11 controlled by loci Mdh2 and Mdh3,
      respectively, were shown to locate in mitochondria, whereas isozyme pp controlled
      by locus Mdh1, in microbodies. All examined samples lack hybrid MDH isozymes,
      which could testify to the interaction between products of nonallelic Mdh genes.
      This can be explained by the localization of nonallelic isozymes in various
      compartments of the cell and organelles.

PMID- 19178084
TI  - [Genetic analysis and location of loci controlling leaf rust resistance of
      introgressive Triticum aestivum x Triticum timopheevii].
AB  - Introgressive lines resulting from crossing common wheat Triticum aestivum with
      the tetraploid T. timopheevii are characterized by effective resistance to leaf
      rust caused by Puccinia triticina Eriks. Molecular analysis using 350 specific
      short sequence repeat (SSR) markers was used to locate the T. timopheevii genome
      to chromosomes 1A, 2A, 2B, 5A, 5B, and 6B. A population of F2 offspring of
      crossing hybrid line 842-2 with common wheat cultivar Skala was obtained for
      mapping the loci controlling leaf rust resistance. Analysis of association of
      phenotypic and genotypic data by means of simple interval mapping (SIM) and
      composite interval mapping (CIM) has shown that the resistance of adult plants is
      determined by two loci in chromosomes 5B and 2A. The major locus QLr.icg-5B
      transferred from T. timopheevii chromosome 5G mapped to the interval of
      microsatellite loci Xgwm408-Xgwm1257 controls 72% of the phenotypic diversity of
      the trait. The other, minor locus QLr.icg-2A located to chromosome 2A at a
      distance of 10 cM from Xgwm312 accounts for 7% of the trait expression.
      Microsatellite markers located near these loci may be used for controlling the
      transfer of commercially valuable loci when new lines and cultivars are created.

PMID- 19178083
TI  - [Comparative genome analysis in pea Pisum sativum L. varieties and lines with
      chromosomal and molecular markers].
AB  - C banding, Ag-NOR staining, FISH with pTa71 (45S rDNA) and pTa794 (5S rDNA), and
      RAPD-PCR analysis were used to study the genome and chromosome polymorphism in
      four varieties (Frisson, Sparkle, Rondo, and Finale) and two genetic lines
      (Sprint-2 and SGE) of pea Pisum sativum L. A comparison of the C-banding patterns
      did not reveal any polymorphism within the varieties. The most significant
      between-variety differences were observed for the size of C bands on satellite
      chromosomes 4 and 7. All grain pea varieties (Frisson, Sparkle, and Rondo) had a
      large C band in the satellite of chromosome 4 and a medium C band in the region
      adjacent to the satellite thread on chromosome 7. C bands were almost of the same
      size in the genetic lines and vegetable variety Finale. In all accessions, 45S
      rDNA mapped to the secondary constriction regions of chromosomes 1, 3, and 5. The
      signal from chromosome 5 in the lines was more intense than in the varieties. Ag
      NOR staining showed that the transcriptional activity of the 45S rRNA genes on
      chromosome 7 was higher than on chromosome 4 in all accessions. No more than four
      Ag-NOR-positive nucleoli were observed in interphase nuclei. Statistical analysis
      of the total area of Ag-NOR-stained nucleoli did not detect any significant
      difference between the accessions examined. RAPD-PCR analysis revealed high
      between-variety and low within-variety genomic polymorphism. Chromosomal and
      molecular markers proved to be promising for genome identification in pea
      varieties and lines.

PMID- 19178085
TI  - [Diversity and individuality of variants of the system of B chromosomes in mice
      Apodemus peninsulae].
AB  - A complicated population system of B chromosomes has been revealed in the
      karyotypes of the East-Asian mouse Apodemus peninsulae over the whole range.
      Based on our previous data for mice from Altai, Siberia, Pribaikal'e, and
      Mongolia and on the results of the present work, we infer that most of animals
      studied (196 out of 312, or 63%) have an individual variant of the B chromosome
      system. Only three mice lacked B chromosomes. New data for 44 A. peninsulae mice
      caught in 2000-2005 in 16 localities of seven regions of Altai, Siberia, and
      Pribaikal'e showed that all of them had individual variants of the system of B
      chromosomes due to different combinations (from 2 to 18 B chromosomes) of five
      classes of B macro- and microchromosomes.

PMID- 19178086
TI  - [Variation of the mitochondrial DNA control region in the populations of southern
      form of Dolly Varden (Salvelinus malma krascheninnikovi) from Sakhalin].
AB  - Analysis of a 551-bp segment of the mitochondrial DNA control region in 23
      individuals from nine populations of Dolly Varden from Sakhalin and three
      individuals from the Shikaribetsu Lake (Hokkaido) revealed the presence of seven
      haplotypes of southern form, along with one haplotype of northern form of Dolly
      Varden. All seven haplotypes of southern Dolly Varden were earlier described in
      the populations from Hokkaido. Nested analysis of molecular variance (AMOVA)
      based on the haplotype frequencies, performed using literature data, suggested
      that, during the glacial epoch, there were three regional population groups of
      Dolly Varden (from eastern and western coasts of Sakhalin, and from Southern
      Primorye). Population groups from Sakhalin and Primorye were clearly separated.
      The differences between two Sakhalin population groups in the mtDNA haplotype
      frequencies were not statistically significant. However, relative to the earlier
      obtained data on microsatellite loci, these differences were statistically
      significant. For the populations of Sakhalin Dolly Varden, the data on
      mitochondrial and microsatellite DNA variation supplement each other.

PMID- 19178087
TI  - [Analysis of the cytochrome P450 (CYP1A1) gene polymorphism in the ethnic groups
      of the Republic of Bashkortostan].
AB  - In three ethnic groups from the Republic of Bashkortostan, Russians (N = 451),
      Tatars (N= 333), and Bashkirs (N= 171), allele, genotype, and haplotype frequency
      distribution patterns of the CYP1A1 gene single nucleotide polymorphisms, A2455G
      and T33801C, were investigated. Substantial interethnic differences in the allele
      frequency distribution patterns of the CYPIA1 polymorphisms A2455G and T3801C
      (chi2 = 15.61, d.f. = 2, P = 0.0001; and chi2 = 22.10, d.f. = 2, P = 0.0001,
      respectively) were observed. Pairwise comparison showed that ethnic groups of
      Tatars and Russians were similar in the A2455G allele frequencies (chi2 = 1.10,
      d.f. = 1, P = 0.30). However, in case of the T3801C marker, statistically
      significant differences were revealed (chi2 = 4.56, d.f. = 1, P = 0.032). At the
      same time, Bashkir ethnic group was found to be statistically significantly
      different from Russians and Tatars in the CYP1A1 polymorphic allele frequency
      distribution patterns (chi2 = 15.74, d.f. = 2, P = 0.0001; and chi2 = 7.47, d.f.
      = 1, P = 0.024, for A2455G, and chi2 = 6.46, d.f. = 1, P = 0.011; and chi2 =
      21.36, d.f. = 1, P = 0.0001, for T3801C). Analysis of the CYP1A1 haplotype
      diversity showed that in terms of the CYP1A1 haplotype frequency distribution
      patterns, Bashkir ethnic group was statistically significantly different from
      both Russians (chi2 = 30.07, d.f. = 3, P = 0.0001) and Tatars (chi2 = 11.28, d.f.
      = 3, P = 0.013). The differences observed were caused by the high frequency of
      haplotype CYP1A1*2B, which was represented by a combination of rare alleles of
      the CYP1A1 polymorphisms A2455G and T3801C in Bashkirs (5.81%). On the other
      hand, the ethnic groups of Russians and Tatars residing in the Republic of
      Bashkortostan were characterized by similar frequencies of the CYP1A1 haplotypes
      (chi2 = 6.322, d.f. = 3, P = 0.127). The data obtained could be used in further
      investigations of the genetic bases of ecology dependant diseases and in the risk
      groups in the Republic of Bashkortostan.

PMID- 19178088
TI  - [Frequency of the 735G --> A mutation of the 5'-splice donor site of intron 14 of
      the dihydropyrimidine dehydrogenase gene (DPYD) in residents of Novosibirsk
      region (Russia) as revealed with fluorescent oligonucleotides].
AB  - A simple method was developed for end-point fluorescence detection of the 735G -
      > A mutation of the 5'-splice donor site of intron 14 of the dihidropyrimidine
      dehydrogenase gene (DPYD). The method was based on allele-specific PCR with
      duplex Scorpion primers. The genotyping results obtained by the fluorescent
      endpoint PCR technique completely coincided with the results obtained by allele
      specific PCR with amplicon detection in agarose gel. Genotyping was performed in
      291 DNA samples from residents of Novosibirsk region (Russia), and two
      heterozygotes (0.69%) were detected.

PMID- 19178089
TI  - [Several copies of insulator from MDG4 can determine the interaction between
      positively and negatively acting regulatory elements and promoter of the
      miniwhite gene of Drosophila melanogaster].
AB  - Fine regulation of complex gene loci in higher eukaryotes is realized through the
      interaction of promoters with enhancers and repressors, which can be located long
      distance from the promoter regulated. A question arises, what mechanisms
      determine proper contacts between the regulatory elements over large distances in
      the genome. It is suggested that the important role in this process is played by
      a special class of regulatory elements, insulators, which block the interaction
      of enhancer and promoter, if they are positioned between them. Furthermore,
      enhancers do not directly inactivate the activities of enhancer and promoter.
      Nevertheless, an enhancer, isolated from one of the promoters by an insulator,
      can activate another, not isolated promoter. The best studied insulator of
      Drosophila melanogaster was found in the 5' regulatory region of retrotransposon
      MDG4. It consists of 12 binding sites for the Su(Hw) protein, which is critical
      for the activity of this insulator. It was demonstrated that Su(Hw) insulator
      could protect the gene expression from the negative influence of heterochromatin
      and from repression, induced by the Polycomb group proteins (Pc proteins). In the
      present study, it was demonstrated that in transgenic lines, two or three copies
      of the Su(Hw) insulator could determine the interaction of the miniwhite enhancer
      and Pc dependant silencer with the miniwhite promoter. Thus, it was first
      demonstrated that insulators could participate in the regulation of the contacts
      between promoter and functionally opposite elements, responsible for either gene
      activation, or repression.

PMID- 19178090
TI  - Validity of self-assessment of oral health among 15-year-olds in Tehran, Iran.
AB  - PURPOSE: The objective of the present study was to compare the self-assessed and
      the clinically determined findings of oral health and their determinants among 15
      year-olds in Tehran, Iran. MATERIALS AND METHODS: A cross-sectional study based
      on World Health Organization criteria and the methods of the Second International
      Collaborative Study was carried out among the 15-year-olds (N = 509). The data
      were based on a self-administered questionnaire and a clinical dental
      examination. RESULTS: Altogether 78% of the 15-year-olds assessed their oral
      health as good or better. Based on self-assessment, 46% reported gingival
      bleeding, 28% reported the need for a filling and 23% for teeth straightening.
      Clinical examinations showed that 40% of the students had sound dentition
      (decayed, missing or filled teeth, DMFT = 0), 40% had current caries (decayed
      teeth, DT > 0), 92% had gingival bleeding and 26% had a definite need for
      orthodontic treatment. Most of those with DMFT = 0 and DT = 0 assessed their oral
      health as good or better. Compared with clinical findings, sensitivity for self
      assessed need for fillings, gingival bleeding and the need for teeth
      straightening were 42%, 49% and 37%, respectively, whereas the corresponding
      specificities were 82%, 80% and 81%, respectively. Good or better self-perceived
      oral health was more likely among those with sound dentition (odds ratio, OR =
      2.1, P = 0.01), with no self-assessed need for fillings (OR = 2.1, P = 0.01),
      with a self-assessed absence of gingival bleeding (OR = 2.9, P < 0.001) or with
      highly educated parents (OR = 1.2, P = 0.007). CONCLUSIONS: When compared with
      clinical evaluations, the students most accurately detected healthy conditions.
      Educating the students on the signs of dental diseases could increase the
      reliability of self-assessment to provide a useful method for reporting oral
      conditions, especially in countries with developing oral health care systems.

PMID- 19178091
TI  - Mothers as facilitators of preadolescents' oral self-care and oral health.
AB  - PURPOSE: This study investigated the role of mothers in their preadolescents'
      oral self-care (OSC) and oral health in Tehran, Iran. MATERIALS AND METHODS: In
      2005, two self-administered questionnaires provided data on a random sample of 9
      year-old children (N = 416) and their mothers. Brushing frequency, use of
      fluoridated dentifrice and the number of sugary snacks between meals served as
      OSC assessment criteria for both children and their mothers. Supervision of the
      child's tooth brushing and control of the child's sugary snacking indicated the
      mother's role that was defined as either active or inactive. Decayed, missing or
      filled teeth (DMFT + dmft) values facilitated the assessment of children's dental
      status in a voluntary clinical examination for children. The child's twice-daily
      tooth brushing, sound dentition and good oral hygiene were taken as the outcome
      measures for evaluating the impact of the mother's role. The chi-square test and
      logistic regression model were used for the analyses. RESULTS: Half of the
      mothers were assessed as active in the supervision of their children's tooth
      brushing. Supervision was clearly more frequently reported by the mothers whose
      own OSC was favourable. In the logistic regression model, the strongest factors
      contributing to the explanation of twice-daily tooth brushing were the child's
      female gender (odds ratio, OR = 1.6; 95% confidence interval, 95% CI = 1.1 to
      2.4) and the mother's active supervision (OR = 1.5; 95% CI = 1.0 to 2.2). Having
      sound dentition was most strongly explained by the mothers' active supervision of
      their children's tooth brushing (OR = 2.4; 95% CI = 1.3 to 4.5). CONCLUSIONS: The
      mothers' supporting role positively reflects on twice-daily tooth brushing and
      sound dentition in preadolescents. More preventive efforts through mothers should
      be considered during the planning of promotion programmes for preadolescents.

PMID- 19178092
TI  - Oral self-care and use of dental services among adults with diabetes mellitus.
AB  - PURPOSE: To investigate the oral health behaviour and the smoking habits among
      diabetic adults with regard to diabetes-related factors and their background
      information. MATERIALS AND METHODS: In 2005, a questionnaire was conducted among
      diabetic adults (N = 299) in Tehran, Iran. The subjects were invited to the
      dental clinic and were asked to complete a self-administered questionnaire. In
      addition to their background information, the questionnaire requested information
      on smoking, oral self-care, dental attendance, year of onset of diabetes and
      organ complications related to diabetes. The data related to the type of diabetes
      and the latest value of glycosylated haemoglobin level (HbA1c) were obtained from
      the patient records at the diabetic clinic. Chi-square test and binary logistic
      regression model were used for statistical analyses. RESULTS: Of all the
      subjects, 29% reported brushing their teeth on a twice-daily basis. Women (P =
      0.05) reported higher frequencies of twice-daily tooth brushing. Subjects with
      moderate diabetic control (HbA1c = 7.6-8.5%) showed the highest rate for twice
      daily tooth brushing (P < 0.001). Of all the subjects, 47% reported having
      visited a clinician within the past 12 months; this rate was the highest among
      those without diabetes-related complications (52% versus 41%; P = 0.05). Subjects
      who had a physician referral were more likely to report having had a dental visit
      within the past 12 months (OR = 4.4; CI = 1.9-10.2). CONCLUSIONS: The present
      results call for improvement in the level of oral self-care and the regularity of
      dental checkups among diabetic adults to compensate for their increased risk for
      oral diseases.

PMID- 19178093
TI  - Development of an oral salutogenic checklist to promote lifelong oral health in
      Japanese adults.
AB  - PURPOSE: The aim of this study was to assess the relative weights of each factor
      related to tooth retention identified in our previous study with an objective of
      developing a risk assessment tool that could be incorporated into a self
      administered oral salutogenic checklist. MATERIALS AND METHODS: Oral health
      status and lifestyle were investigated in 777 subjects aged > or = 20 years.
      Eleven items that had a statistically significant odds ratio of being related to
      the number of retained teeth in our previous study were identified. Discriminant
      analysis was used to calculate the scores for each item. RESULTS: Based on the
      discriminant analysis, the variables affecting tooth retention, from the most to
      the least important, were 'gum swelling' (1.241), followed by 'toothache' (0.766)
      and 'do you have any hobbies' (0.691). Based on the above analysis, a total of 20
      points were allocated in proportion to the ranges. The final oral salutogenic
      score (OSS) was swollen gums (4), toothache (3), frequency of between-meal snacks
      (3), having some hobbies (3), having a family clinician (2), consulting a
      clinician when having dental symptoms (1), bleeding gums (1), frequency of tooth
      brushing (1), having one's own toothbrush (1) and smoking (1). CONCLUSIONS: A
      self-administered checklist for the OSS was designed. The first part contains a
      list of questions for the participants to fill out. The second part offers
      comments depending on the range of score values. The suggestions include advice
      to decrease or to stop the behaviours for which the subject obtained zero points.

PMID- 19178094
TI  - Prevalence, intensity and impact of dental pain in 5-year-old preschool children.
AB  - PURPOSE: The aim of this study was to assess the impact of clinical oral health
      conditions, and the prevalence, intensity and the impact of dental pain on daily
      living among 5-year-old preschool children. MATERIALS AND METHODS: A cross
      sectional survey was carried out on a sample of 578 children attending preschools
      in Belo Horizonte, Brazil. Data were collected by means of a pretested
      questionnaire given to the parents and a visual analogue scale of faces applied
      to the children. The children underwent dental examinations. RESULTS: According
      to the parents' reports, the lifetime prevalence of dental pain was 25.0% (95%
      confidence interval, 95% CI = 21.4 to 28.6), and dental pain caused crying in
      16.8% (95% CI = 13.6 to 19.9) of the children; 10.7% (95% CI = 8.1 to 13.3) of
      children had dental pain in the 2 months prior to the dental examination. Among
      this group of children with dental pain, 59.3% experienced a negative impact as a
      result of pain. The following clinical conditions had mostly caused dental pain
      in the 2 months prior to the dental examination: root remnants, fistula and pulp
      caries. This recent pain resulted in a visit to the clinician in 13.6% of the
      children. CONCLUSIONS: Prevalence, intensity and the impact of dental pain in 5
      year-old children were high in Belo Horizonte, Brazil. Dental pain assessed in
      the present study was associated with avoidable pathological factors. However,
      only few children were treated professionally for the dental pain they were
      experiencing. Public policies should be developed and implemented to promote
      fair, comprehensive treatment for the population.

PMID- 19178095
TI  - Clinical, socioeconomic and patient outcomes of intensive versus conventional
      scaling and root planing in the treatment of periodontal infection.
AB  - PURPOSE: To compare the two non-surgical periodontal treatment methods with
      regard to socioeconomic aspects, treatment results and complications. METHODS AND
      RESULTS: Twenty-five patients were randomly divided into two groups for non
      surgical treatment consisting of scaling and root planing. One group had
      intensive treatment (InT) performed within 24 h and the other group received
      conventional treatment (CoT) with one treatment session a week for 4 weeks. All
      the patients rinsed their mouth with chlorhexidine 0.2% after each treatment
      session for 5 weeks. The investigation before and after the treatment was
      performed by the same clinician blinded to the treatment modalities, and all the
      treatments were performed by the same dental hygienist. Treatment had
      significantly reduced the number of pockets in both the treatment groups, but
      there was no difference between the two treatment modalities regarding pocket
      reduction or reported discomfort/pain graded on the visual analogue scale. Only
      one patient receiving the InT was not satisfied. However, in the CoT group six
      patients answered that they would have preferred the InT, whereas the remaining
      patients answered that it did not matter whether they received InT or CoT. The
      patients in the CoT group consumed more analgesics after the treatment. The mean
      total travelling time for the InT group was 113 min compared with 357 min for the
      CoT group. CONCLUSIONS: Most patients preferred the InT if they were to undergo
      the treatment again. Furthermore, InT resulted in a substantial socioeconomic
      gain with no difference in the treatment result and the complication rate
      compared with CoT.

PMID- 19178096
TI  - Efficacy of plaque removal by two types of toothpick.
AB  - PURPOSE: To compare the efficacy of two types of interdental device, namely
      triangular woodstick and round toothpick, in the removal of interproximal dental
      plaque. MATERIALS AND METHODS: This study had a split-mouth design and was
      conducted on 15 individuals. After 72 h of dental plaque accumulation, the dental
      plaque was quantified by the Quigley-Hein Plaque Index (QHPI). Two quadrants were
      then randomly assigned for the use of triangular woodstick and the other two for
      the use of round toothpick. After the use of toothpicks, the QHPI was re
      evaluated by a calibrated examiner, blinded to the types of toothpick used. The
      mean values of QHPI were calculated for both types of toothpick, before and after
      use. Comparison within and between groups was performed by the paired t test, at
      a significance level of 0.05. RESULTS: Both the toothpicks provided significant
      reduction of QHPI, without any statistically significant difference between the
      types of toothpick (from 3.31 +/- 0.61 to 2.42 +/- 0.60 using triangular
      woodsticks and from 3.19 +/- 0.71 to 2.24 +/- 0.54 using round toothpicks, in the
      initial and the final periods, respectively). Individual comparison of proximal
      aspects by observation from buccal proximal and palatal/lingual proximal aspects
      revealed that round toothpicks removed a greater amount of plaque than triangular
      woodsticks in areas that were analysed by observation from the palatal/lingual
      proximal aspect. CONCLUSIONS: No statistically significant differences were found
      between round toothpicks and triangular woodsticks in the removal of
      supragingival plaque.

PMID- 19178097
TI  - Promoting caries arrest in children with silver diamine fluoride: a review.
AB  - Although there has been a decrease in the prevalence and the severity of dental
      caries in children over the past few decades, the benefits have not been equally
      shared by many low-income or underserved children in many industrialised
      countries, or children in developing countries. Dental caries is still the most
      common and challenging dental disease in children for a clinician to treat.
      Silver diamine fluoride (SDF) has been in use to arrest dental caries in many
      countries. A 38% (44,800 ppm fluoride ions) SDF solution is commonly used to
      arrest caries in primary teeth of children, especially those children who are
      young and difficult to manage. Application of SDF to arrest dental caries is a
      non-invasive procedure that is quick and simple to use. However, it stains the
      carious teeth and turns the arrested caries black. It also has an unpleasant
      metallic taste that is not liked by patients, especially children. The low cost
      of SDF and its simplicity in application suggest that SDF is an appropriate
      therapeutic agent for use in community dental health projects. Reports of
      available studies found no severe pulpal damage after SDF application. The
      current literature suggests that SDF can be an effective agent in preventing new
      caries and in arresting dental caries in the primary teeth of the children. It
      can be used to arrest caries progression in very young children who are less
      cooperative, and it allows definitive restoration to be performed when they grow
      older and become more receptive to dental procedures.

PMID- 19178098
TI  - Band cementation materials: solubility and fluoride release.
AB  - PURPOSE: The aim of this study was to evaluate the solubility and the fluoride
      release of different materials used for orthodontic band cementation in different
      solutions and at different times. MATERIALS AND METHODS: Three materials were
      selected: Ultra Band-Lok (UBL); RelyX (RLX) and Ketac-Cem (KTC). Sixteen standard
      samples from each material were prepared, according to the manufacturers'
      instructions. The samples were stored in two different solutions (n = 8): 0.9%
      saline solution (pH 7.0) and 0.1 mol/l lactic acid (pH 4.0). The storage
      solutions were changed after 24 h and after 7, 15 and 30 days. The fluoride
      release was determined with an ion-specific electrode (Analion). For the
      solubility evaluation, the formula Wsl = (m1-m2)/V was used to determine the loss
      of mass. Data were submitted for statistical analysis using the non-parametric
      Kruskal-Wallis test. RESULTS: With respect to the solubility, immersion in lactic
      acid increased the solubility when compared with saline solution (P < 0.01). In
      both the solutions, there were differences among materials (P < 0.01) with the
      following rankings: UBL < RLX < KTC for lactic acid and UBL < RLX < KTC for
      saline solution. The ranking of fluoride release was UBL < KTC < RLX. In the two
      tested solutions, RLX exhibited the highest fluoride release (P < 0.01), whereas
      KTC showed more fluoride release than that of UBL (P < 0.05). Fluoride release
      decreased over time and the storage solution influenced the fluoride-releasing
      capacity of some materials. CONCLUSIONS: It was found that fluoride release was
      influenced by storage solution, materials and immersion time. Materials and
      storage solution were the significant factors for solubility.

PMID- 19178099
TI  - Apgar index as a correlate of enamel defects of primary dentition.
AB  - PURPOSE: Enamel defects are serious challenges because of their unaesthetic
      appearance, dentinal sensitivity and the subsequent susceptibility to dental
      caries. Apgar index (AI) is used for postnatal, general, neural and behavioural
      assessment of newborns. The aim of the present study was to investigate the
      correlation of AI with the enamel defects of primary dentition. MATERIALS AND
      METHODS: A total of 181 subjects (95 females and 86 males) aged 3 to 5 years were
      randomly selected. Subjects with a history of systemic or debilitating diseases
      or local confounding factors, for example traumatic habits leading to enamel
      abrasion, were excluded. According to the modified index for developmental enamel
      defects, visual and tactile examinations of the entire primary dentition (buccal,
      lingual/palatal and incisal/occlusal) were performed. Teeth with caries lesions
      and restorations were excluded from the examination. After collection of the data
      regarding AIs of the subjects, statistical analysis was performed based on the
      Spearman and Mann-Whitney U tests. RESULTS: Enamel hypoplasia and
      hypocalcification were negatively correlated with the AI (P < 0.05). Moreover,
      the number of teeth exhibiting enamel defects was significantly lower in subjects
      with higher AI (P < 0.05). The effect of gender on the distribution of enamel
      defects as a covariate was not statistically significant (P > 0.05). CONCLUSIONS:
      AI is inversely correlated with enamel defects of primary dentition. Both quality
      and quantity of enamel defects of primary dentition are higher in children with
      lower AI, delineating a high-risk group demanding more stringent preventive
      measures.

PMID- 19178100
TI  - Effect of xylitol on an in vitro model of oral biofilm.
AB  - PURPOSE: The aim of the present study was to examine whether xylitol, at
      different concentrations, inhibits the formation of an experimental model of oral
      biofilm. MATERIALS AND METHODS: Biofilms of six bacterial species (Streptococcus
      mutans, Streptococcus sobrinus, Lactobacillus rhamnosus, Actinomyces viscosus,
      Porphyromonas gingivalis and Fusobacterium nucleatum) were prepared on
      hydroxyapatite (HA) discs according to the Zurich Biofilm Model. Xylitol was
      tested at two concentrations, 1% and 3%. At the end of their designated
      incubation times, some HA discs were destined for confocal laser scanning
      microscopy (CLSM) and the others were harvested using a sterile surgical
      instrument. Aliquots of harvested biofilms were diluted and plated onto specific
      media. After a 48-h anaerobic incubation at 37 degrees C, the colony-forming
      units (CFUs) were counted. RESULTS: CLSM images showed that only a small amount
      of isolated bacteria was observed on the surface of HA discs. Culture of
      harvested biofilms showed an inhibition in the growth of different species
      included in the biofilms. CONCLUSIONS: Xylitol has a clear inhibitory effect on
      the formation of the experimental biofilms. This study shows that xylitol is not
      only efficient in inhibiting the acid production of cariogenic bacteria, but also
      in preventing the formation of a multispecies biofilm; it confirms the relevance
      of the use of this polyol for the prevention of oral diseases caused by dental
      plaque.

PMID- 19178101
TI  - Oral health status and effectiveness of caries prevention programme in
      kindergartens in Kaunas city (Lithuania).
AB  - PURPOSE: To describe oral health status and to evaluate the effectiveness of a
      caries prevention programme in preschool children. MATERIALS AND METHODS: A
      sample of 1656 3- to 7-year-old children were examined in kindergartens in 2002,
      and 411 3-year-old children were then selected to participate in the prevention
      programme. The test group A (n = 156), group B (n = 118), and the control group
      (n = 137) were defined for the study. For test group A, supervised toothbrushing
      was prescribed and for test group B, fluoride gel applications were used. For the
      control group, children did not undergo any of the aforementioned procedures.
      Dental caries was assessed according to the World Health Organization (WHO)
      criteria, and oral hygiene according to the Greene-Vermillion simplified oral
      hygiene index. Preventive programmes were based on oral hygiene instructions,
      supervised daily toothbrushing, and fluoride gel applications. The relationship
      between oral hygiene and severity of dental caries was determined by using
      Fisher's test. RESULTS: The prevalence of dental caries varied between 39.7% and
      90.8%, and the decayed, missing, and filled teeth (dmf-t) varied between 1.3 +/-
      0.16 and 5.0 +/- 0.24. Oral hygiene was satisfactory in 43.2% of children. During
      the 3 years of the programme, a significant difference was found between the test
      and the control groups. The reduction in test group A was 45.4% and in test group
      B was 60.1%. CONCLUSIONS: The prevalence and severity of dental caries among the
      examined children increased with age, and was lower in both the test groups
      compared with the control group. The professional fluoride applications and
      proper oral hygiene showed the most effective results in caries prevention.

PMID- 19178103
TI  - Are the kids alright?

PMID- 19178102
TI  - Influence of clinicians' socio-demographic, professional and educational
      variables on their compliance with preventive measures against hepatitis B and C.
AB  - PURPOSE: To investigate the influence of a number of variables regarding
      clinicians' gender, social class, length of time since graduation and the level
      of knowledge on their use of available preventive measures against hepatitis B
      and C. MATERIALS AND METHODS: A cross-sectional questionnaire-based survey was
      carried out involving a random and representative sample (n = 319) of the
      clinicians working in Recife, Pernambuco, North-East Brazil. The participants
      were interviewed by means of a questionnaire, prepared and pretested by the
      researchers. Pearson's chi-square and Fisher's exact tests were used in the
      statistical analyses (significance level: 5%). RESULTS: Female clinicians were
      found to make more frequent use of equipment such as lab coats, scrub caps and
      masks (P = 0.0357). With regard to lab coat use in relation to social class, it
      was seen that clinicians from social class B used it less (P = 0.0077). The
      length of time since graduation was seen to be connected with the use of scrub
      caps (P = 0.0003), coating of equipment with polyvinyl chloride plastic film (P =
      0.037), use of alcohol for cleaning equipment (P = 0.0012), two-handed recapping
      of needles (P < 0.0001) and immunisation (P = 0.003), showing that those who
      graduated most recently were more likely to take adequate infection control
      steps. The fact that clinicians had been informed about hepatitis B and C, and
      also their knowledge about its contagion, was positively associated with their
      levels of vaccination against HBV (P = 0.0313 and 0.0108, respectively).
      CONCLUSIONS: The adherence to preventive practices against hepatitis B and C was
      shown to be connected with the clinicians' socio-demographic, professional and
      educational variables.

PMID- 19178104
TI  - What breast-cancer survivors can expect.

PMID- 19178105
TI  - Two shots for chicken pox now.

PMID- 19178106
TI  - We protect kids from everything but fear.

PMID- 19178107
TI  - Taking the junk out of junk food.

PMID- 19178108
TI  - A new ambivalence.

PMID- 19178109
TI  - Just don't call me Mr. Mom.

PMID- 19178110
TI  - The darkest secret.

PMID- 19178111
TI  - Globalization of food systems in developing countries: impact on food security
      and nutrition.

PMID- 19178112
TI  - Validation of a comprehensive infection control program in LTC.

PMID- 19178113
TI  - Facility culture in relation to "minimal lift" programs.

PMID- 19178114
TI  - Treatment for patients with gastroesophageal reflux disease.

PMID- 19178115
TI  - Urinary incontinence in long-term care facilities: current clinical practice.

PMID- 19178116
TI  - The treatment of heart failure in the elderly patient with comorbidities.

PMID- 19178117
TI  - Improving COPD management in the nursing home--part 2.
AB  - COPD is a disease that affects a significant number of residents in nursing
      facilities. This disease is partially reversible, especially with early diagnosis
      and proper intervention. The severity of disease varies from resident to
      resident. The nursing staff has a significant role in identifying, assessing, and
      managing residents with COPD. Training and education are essential to success.
      Appropriate use of nonpharmacological and pharmacological modalities can slow the
      progression of disease and improve a resident's ADLs and QOL.

PMID- 19178118
TI  - Integrative care--weighing in.

PMID- 19178119
TI  - Methods of economic evaluation for the German Statutory Healthcare System.

PMID- 19178120
TI  - The applicability and generalizability of findings from clinical trials for
      health-policy decisions.
AB  - Randomized controlled trials provide unbiased estimates of treatment effect
      through reducing the attribution of observed differences in outcome to the play
      of chance or the treatment of interest. Issues in the design of randomized trials
      may lead to a dilution or magnification of treatment effect when compared with
      clinical practice. The intention-to-treat principle will lead to dilution in the
      treatment effect, while the selective recruitment of adherent and motivated
      subjects may lead to enhanced treatment effect estimates. Observational data, on
      the other hand, may reflect clinical practice but cannot provide unbiased
      estimates of treatment effect. Health policy may be informed by the combination
      of randomized and observational data in decision-analytic models.

PMID- 19178121
TI  - Is medication review by primary-care pharmacists for older people cost
      effective?: a narrative review of the literature, focusing on costs and benefits.
AB  - The nature, definition and history of medication review of long-term conditions
      and treatment is discussed. A literature search for studies of medication review
      of older people in primary care by pharmacists yielded 16 reports of studies in
      English, and only ten of these were randomized controlled trials. Extracting
      meaningful conclusions from the data was problematic because of variations in the
      nature of the review described, the populations studied, the outcome data
      measured and the evaluation criteria used. There is a dearth of economic
      measurement and often inadequate descriptions of the interventions performed.
      Those interventions that were described in detail varied in the skills, training
      and approach of the pharmacists. Therefore, there was no possibility of
      aggregating results of studies, and the review conclusions are based on trends
      and impression rather than meta-analysis. There was no suggestion in any reports
      that patients were harmed by the interventions, and some consistency in
      suggesting that falls and hospital admissions might be reduced with modest cost
      savings, at least in terms of drug costs. No studies reported a benefit in terms
      of mortality, mental capacity or activities of daily living. The authors conclude
      that clinical medication review is probably of value and may be cost effective,
      but propose a large-scale, long-term, multicentre, collaborative clinical trial
      with carefully chosen (and clearly described) interventions and outcome measures
      to confirm this.

PMID- 19178122
TI  - Statin therapy in rheumatoid arthritis: a cost-effectiveness and value-of
      information analysis.
AB  - HMG-CoA reductase inhibitors (statins) are potentially excellent candidate agents
      for patients with rheumatoid arthritis (RA). They reduce both cardiovascular
      risks and RA disease activity. To evaluate the potential long-term effects of
      statin therapy among patients with RA, and to determine their associated cost
      effectiveness by incorporating both the cardiovascular and the anti-rheumatic
      benefits. A Markov decision-analytic model was developed to simulate
      cardiovascular and RA disease profiles over time. The impact of statin therapy
      was estimated by adjusting the risk of coronary heart disease (CHD) events and
      changes in the RA Disease Activity Score (DAS28), based on the results of a
      randomized trial. The benefits (QALYs) and costs (in year 2005 values) were
      evaluated from a US payer perspective. A full uncertainty analysis, including a
      value-of-information (VOI) analysis, was undertaken to evaluate the importance of
      individual parameters. Using a 10-year time horizon, the additional cost and
      QALYs of statin therapy were estimated to be USD4690 and 0.44 QALYs,
      respectively, resulting in an incremental cost-effectiveness ratio (ICER) of
      USD10 650 per QALY (95% CI 1525, 156 565). The QALY gain associated with statin
      therapy depended more on the anti-rheumatic effects of statin therapy than on its
      cardiovascular prevention effect. The VOI analysis found the long-term benefit of
      statin therapy (i.e. >or=12 months) and the consequent impact on quality of life
      to be the most uncertain and, therefore, influential parameters. Our analysis
      indicates that the dual anti-inflammatory/cardiovascular benefits of statins
      could make this therapy highly cost effective in RA. However, uncertainties
      remain in the available data, warranting further research on refining the precise
      RA disease-activity benefits and health-utility changes associated with statin
      therapy, at least over a 12-month period.

PMID- 19178123
TI  - Treating relapsing multiple sclerosis with subcutaneous versus intramuscular
      interferon-beta-1a: modelling the clinical and economic implications.
AB  - The EVIDENCE trial concluded that administering high-dose/high-frequency
      subcutaneous (SC) interferon-beta-1a (IFNb1a) was more effective in preventing
      relapses among patients with relapsing multiple sclerosis (MS) than low-dose
      weekly intramuscular (IM) IFNb1a after 64 weeks. This analysis utilized discrete
      event simulation (DES) to model the potential longer-term clinical and economic
      implications of this trial. A DES predicting the course of relapsing MS and
      incorporating the effect of IFNb1a therapy was developed. The model began by
      randomly reading in actual patient data from the trial to create 1000 patients.
      Each simulated patient was replicated - one was assigned to receive SC IFNb1a
      three times a week and the other to receive IM IFNb1a once a week. During the
      simulation, patients may (i) experience relapses, with associated short- and long
      term impacts on costs and disability; (ii) develop new T2 lesions detected by a
      magnetic resonance imaging scan; (iii) discontinue treatment because of adverse
      events or lack of response; (iv) advance to secondary progressive MS; or (v) die.
      Model inputs were mainly obtained from the EVIDENCE trial, but were taken from
      published literature if they could not be obtained from the trial. Direct medical
      costs ($US, year 2006 values) to the US payers were primarily obtained by
      updating a published cost analysis. Costs and benefits were discounted at 3% per
      annum. Extensive sensitivity analyses were conducted to test the robustness of
      the model results. Based on 100 replications of 1000 patient pairs over 4 years,
      SC IFNb1a was predicted to enable more patients to avoid relapse (216 vs 147).
      Total mean costs per patient (discounted) were $US79 890 with SC IFNb1a versus
      $US74 485 with IM administration, a net increase of $US5405 per patient. However,
      SC IFNb1a was estimated to prevent 0.50 relapses and save 23 relapse-free days
      per patient, yielding incremental cost-effectiveness ratios of $US10 755 per
      relapse prevented and $US232 per relapse-free day gained. Sensitivity analyses
      revealed that the result was most sensitive to the treatment efficacy, model time
      horizon and cost of IFNb1a treatment. Based on the results observed in the
      EVIDENCE trial, the model predicted that SC IFNb1a would yield greater health
      benefits over 4 years than IM IFNb1a, at a cost that would seem to be a
      reasonable trade-off.

PMID- 19178124
TI  - Cost effectiveness of high-dose chemotherapy with autologous stem cell support as
      initial treatment of aggressive non-Hodgkin's lymphoma.
AB  - The GOELAMS 072 study showed that first-line high-dose chemotherapy (HDT) with
      peripheral blood stem cell transplant (PBSCT) support was superior to the
      standard chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine and
      prednisone; CHOP) in adults with aggressive non-Hodgkin's lymphoma (NHL). The aim
      of the study was to evaluate the pharmacoeconomic profile of HDT with PBSCT
      support relative to standard CHOP therapy as first-line treatment in adults with
      aggressive NHL. We performed a cost-effectiveness analysis from the French Public
      Health Insurance perspective, restricted to hospital costs (euro, year 2008
      values). The clinical effectiveness criterion was censured overall survival (OS)
      difference after a median follow-up of 4 years for the entire cohort. A total of
      197 patients were included (CHOP, n = 99; HDT, n = 98). Uncertainty was assessed
      using non-parametric bootstrap simulations and various scenario analyses. Five
      year OS did not differ significantly between groups for the entire cohort.
      Nevertheless, subgroup analyses appeared to be more relevant for decision making:
      among patients with a high-intermediate risk according to the age-adjusted
      International Prognostic Index (IPI), HDT yielded a significantly higher 5-year
      OS than CHOP (74% vs 44%; p = 0.001). Among these patients, the mean censured OS
      survival, adjusted for time discounting and quality of life (QOL), increased with
      HDT by 1.20 years (95% CI 1.19, 1.21). The cost per life-year saved with HDT was
      estimated as euro34 315 (95% CI 32 683, 35 947) in this subgroup. Results
      suggested that HDT with PBSCT support might be considered a cost-effective
      strategy among patients with high-intermediate-risk NHL according to the age
      adjusted IPI. Its place and its cost effectiveness potential versus, or in
      combination with, rituximab still need further research.

PMID- 19178125
TI  - Comparing the cost effectiveness of risperidone and olanzapine in the treatment
      of schizophrenia using the net-benefit regression approach.
AB  - To estimate the cost effectiveness of olanzapine and risperidone for the
      treatment of schizophrenia in Belgium. Data were retrieved from a prospective,
      observational, non-randomized, follow-up survey. Clinical investigators assigned
      265 patients with schizophrenia to either olanzapine (n = 136) or risperidone (n
      = 129). Patients were followed up for 2 years. Total healthcare costs were
      determined from the public payer perspective and calculated by multiplying
      resource use with official tariffs; effectiveness of the drugs was measured with
      the EQ-5D. This study uses a net-benefit regression approach to accommodate for
      baseline differences between treatment groups and uncertainty. Total 2-year costs
      were very similar for patients receiving risperidone and olanzapine (euro20
      915.33 and euro20 569.69, respectively; p = 0.925) [year 2002 values]. The health
      condition of the patients receiving risperidone was better than that of patients
      receiving olanzapine but not significantly so (1.46 and 1.41, respectively; p =
      0.191). Simple ordinary least squares (OLS) regressions indicated that, for
      lambda = euro40 000, we could not reject the null hypothesis that the drugs
      provide similar net monetary benefits to the patient (risperidone vs olanzapine
      euro2046.95; p = 0.656). When we controlled for several patient characteristics,
      risperidone moved further away from olanzapine but the difference did not reach
      statistical significance (risperidone vs olanzapine euro3198.07; p = 0.595).
      Numerous sensitivity analyses confirmed the robustness of the results. Results of
      this study suggest that it is important to control for baseline patient
      characteristics when performing a cost-effectiveness analysis. No significant
      difference in net monetary benefit was found between risperidone and olanzapine.

PMID- 19178126
TI  - Estimating the cost of diabetes mellitus-related events from inpatient admissions
      in Sweden using administrative hospitalization data.
AB  - To estimate short- and long-term costs of inpatient hospitalization in Sweden for
      major diabetes mellitus-related events. Costs were estimated using administrative
      hospital data from the Swedish National Board of Health and Welfare, which is
      linked to the Swedish National Diabetes Register. Data were available for 179 749
      patients with diabetes in Sweden from 1998 to 2003 (mean and median duration of 6
      years' follow-up). Costing of inpatient admissions was based on Nordic diagnosis
      related groups (NordDRG). Multiple regression analysis (linear and generalizing
      estimating equation models) was used to estimate inpatient care costs controlling
      for age, sex and co-morbidities. The data on hospitalizations were converted to
      costs (euro) using 2003 exchange rates. The average annual costs (linear model)
      associated with inpatient admissions for a 60-year-old male in the year the first
      event first occurred were as follows: euro6488 (95% CI 5034, 8354) for diabetic
      coma; euro6850 (95% CI 6514, 7204) for heart failure; euro7853 (95% CI 7559,
      8144) for non-fatal stroke; euro8121 (95% CI 7104, 9128) for peripheral
      circulatory complications; euro8736 (95% CI 8474, 9001) for non-fatal myocardial
      infarction (MI); euro10 360 (95% CI 10 085, 10 643) for ischaemic heart disease;
      euro11 411 (95% CI 10 298, 12 654) for renal failure; and euro14 949 (95% CI 13
      849, 16 551) for amputation. On average, the costs were higher when co-morbidity
      was accounted for (e.g. MI with co-morbidity was twice as costly as MI alone).
      Average hospital inpatient costs associated with common diabetes-related events
      can be estimated using panel data regression methods. These could assist in
      modelling of long-term costs of diabetes and in evaluating the cost effectiveness
      of improving care.

PMID- 19178127
TI  - Combination therapy as first-line treatment for hypertension.
AB  - Systemic hypertension is a long-term risk factor for the development of
      atherosclerotic vascular disease and when uncontrolled is a short-term trigger of
      acute vascular events such as acute coronary syndromes and stroke. Thus, rapid
      reduction in BP is desirable. Patients at high risk for vascular disease, such as
      those with diabetes mellitus, have aggressive goal BP targets because studies
      have shown that achieving these targets reduces events. Given the dual goals in
      high-risk patients of reducing BP quickly and to aggressively low targets, the
      classic 'step therapy' of one drug titrated at a time to reduce BP is inadequate.
      Combination therapy with at least two potent medications makes more sense, and
      manufacturers are now increasing their offerings of single-pill combinations for
      hypertension. Combination pills are popular with patients and increase compliance
      with therapy. Many believe that renin-angiotensin aldosterone system (RAAS)
      blockers are the cornerstone of hypertension treatment in patients at high risk
      for vascular disease. The newer combination pills include a RAAS blocker and
      diuretics or a long-acting calcium channel antagonist (CCA). Recent studies have
      shown that a RAAS blocker plus a dihydropyridine CCA is superior to older
      diuretic-based combinations for preventing cardiovascular events. These
      considerations support a new approach to the higher risk hypertensive patient:
      effective doses of RAAS blocker/CCA combination pills to rapidly lower BP to
      <130/80 mmHg.

PMID- 19178128
TI  - Non-hemodynamic effects of organic nitrates and the distinctive characteristics
      of pentaerithrityl tetranitrate.
AB  - Organic nitrates are among the oldest and yet most commonly employed drugs in the
      long-term therapy of coronary artery disease and congestive heart failure. While
      they have long been used in clinical practice, our understanding of their
      mechanism of action and side effects remains incomplete. For instance, recent
      findings provide evidence of previously unanticipated, non-hemodynamic properties
      that include potentially beneficial mechanisms (such as the induction of a
      protective phenotype that mimics ischemic preconditioning), but also toxic
      effects (such as endothelial and autonomic dysfunction, rebound angina,
      tolerance). To date, the most commonly employed organic nitrates are isosorbide
      mononitrate, isosorbide dinitrate, and nitroglycerin (glyceryl trinitrate).
      Another organic nitrate, pentaerithrityl tetranitrate (PETN), has long been
      employed in eastern European countries and is currently being reintroduced in
      Western countries. In light of their wide use, and of the (re)introduction of
      PETN in Western markets, the present review focuses on the novel effects of
      organic nitrates, describing their potential clinical implications and discussing
      differences among different compounds. We believe that these recent findings have
      important clinical implications. Since the side effects of organic nitrates such
      as nitroglycerin and isosorbides appear to be mediated by reactive oxygen
      species, care should be taken that drugs with antioxidant properties are co
      administered. On the other hand, efforts should be made to clinically exploit the
      preconditioning effects of these drugs.

PMID- 19178129
TI  - Management of angina pectoris: the role of spinal cord stimulation.
AB  - Progress in prevention as well as drug and interventional therapy has improved
      the prognosis of patients with cardiovascular disorders. Many patients at risk
      have advanced coronary artery disease (CAD), have had multiple coronary
      interventions, and present with significant co-morbidity. Despite adequate risk
      factor modulation and often several revascularization procedures, some of these
      patients still have refractory angina pectoris. Apart from advanced CAD and
      insufficient collateralization, the cause is often endothelial dysfunction. For
      this situation, one treatment option is neuromodulation. Controlled studies
      suggest that, in patients with chronic refractory angina pectoris, spinal cord
      stimulation (SCS) provides a relief from symptoms equivalent to that provided by
      surgical therapy, but with fewer complications and lower rehospitalization rates.
      SCS may result in significant long-term pain relief with improved quality of
      life. In patients with refractory angina undergoing SCS, some studies have shown
      not only a symptomatic improvement, but also a decrease in myocardial ischemia
      and an increase in coronary blood flow. Discussion is ongoing as to whether this
      is a direct effect on parasympathetic vascodilation or merely a secondary
      phenomenon resulting from increased physical activity following an improvement in
      clinical symptoms. Results from nuclear medical studies have sparked discussion
      about improved endothelial function and increased collateralization. SCS is a
      safe treatment option for patients with refractory angina pectoris, and its long
      term effects are evident. It is a procedure without significant complications
      that is easy to tolerate. SCS does not interact with pacemakers, provided that
      strict bipolar right-ventricular sensing is used. Use in patients with implanted
      cardioverter defibrillators is under discussion. Individual testing is mandatory
      in order to assess optimal safety in each patient.

PMID- 19178130
TI  - Cardiovascular outcomes in high-risk patients without heart failure treated with
      ARBs: a systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Angiotensin II type 1 receptor antagonists (ARBs) are
      widely used as a substitute for angiotensin-converting enzyme inhibitors (ACEIs)
      to treat patients without heart failure, but their effect on cardiovascular
      morbidity and mortality has not been clearly determined. A systematic review and
      meta-analysis was undertaken to determine the impact of ARBs on cardiovascular
      outcomes in high-risk patients without heart failure. METHODS: A computerized
      literature search was carried out using PubMed, the Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, and EMBASE, from
      January 1990 to April 2008. The following search terms were used: 'hypertension',
      'clinical trial', 'sartan', 'ARB', 'angiotensin receptor antagonist', 'losartan',
      'candesartan', 'valsartan', 'irbesartan', 'eprosartan', 'telmisartan',
      'olmesartan', 'coronary disease', 'coronary heart disease', 'myocardial
      infarction', 'cardiovascular disease', 'cerebrovascular disease', and 'stroke'.
      Criteria for inclusion of clinical trials in our meta-analysis were the use of a
      randomized control group not receiving an ARB and the availability of outcome
      data for any one of four endpoints: myocardial infarction (MI), stroke,
      cardiovascular death, and all-cause death (these were not always pre-specified
      endpoints in all trials). Out of 45 potentially relevant studies, 37 trials met
      the inclusion criteria. We tabulated all occurrences of these four adverse
      outcomes. RESULTS: Homogenous subgroups were combined by means of a fixed-effects
      model, while heterogenous subgroups were not combined. In the subgroup without
      heart failure, ARBs, when compared with the control group, had an odds ratio of
      1.09 (95% CI 1.00, 1.18; p = 0.05) for MI. Other endpoints, namely,
      cardiovascular death and all-cause death, did not reach statistical significance.
      There was a clear trend for fewer strokes in the ARB group, but these studies
      were clearly heterogenous, and therefore a pooled risk estimate was not computed.
      CONCLUSION: After pooling more than 89 000 patients, there is no evidence to
      suggest that ARBs confer cardiovascular protection akin to ACEIs, and the results
      that emerged are not in favor of ARB therapy in terms of its use as a substitute
      for ACEIs in non-heart failure patients. ARBs may have a small benefit in terms
      of stroke risk, but the studies are heterogenous, making it very difficult to
      quantify this effect. Given that ACEIs protect against both stroke and MI,
      caution is advised in the use of ARBs as a substitute for ACEIs in patients
      without a heart failure indication, who are tolerant of an ACEI.

PMID- 19178131
TI  - Extended dalteparin prophylaxis for venous thromboembolic events: cost-utility
      analysis in patients undergoing major orthopedic surgery.
AB  - BACKGROUND: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are
      manifestations of venous thromboembolic events (VTEs). Patients undergoing major
      surgical procedures such as total hip replacement (THR), total knee replacement
      (TKR), and hip fracture surgery (HFS) are at an elevated risk for VTEs. The
      American College of Chest Physicians' (ACCP) guidelines recommend that such
      patients receive thromboprophylaxis for at least 10 days. In patients undergoing
      THR or HFS, extended prophylaxis for up to 28-35 days is the recommended approach
      for those at high risk of thromboembolic events. The NAFT (North American Fragmin
      Trial) compared the prophylactic efficacy of dalteparin with that of warfarin
      during the in-hospital period, and with that of placebo during the period of
      hospital discharge until day 35 postsurgery, in patients who underwent total hip
      arthroplasty. During both the in-hospital and the postdischarge time periods,
      dalteparin significantly reduced the occurrence of DVT. Given the clinical
      relevance of these results, the low specificity of the ACCP recommendations
      regarding optimal prophylaxis duration, and the importance of optimizing the
      efficiency of DVT prophylaxis in the practice setting, a cost-utility analysis
      was conducted comparing dalteparin 10-day and 35-day (extended) with a warfarin
      10-day protocol, in patients undergoing major orthopedic surgeries such as THR,
      TKR, or HFS. DESIGN AND SETTING: A three-arm decision model was developed using
      the prevalence of symptomatic DVT from NAFT publications, epidemiologic studies,
      and published meta-analyses. Healthcare resource use was abstracted from a survey
      of clinicians and from the economic literature. Utility estimates were obtained
      by interviewing a sample of 24 people from the general public using the time
      trade-off technique. The clinical, economic and utility data were then used to
      estimate the cost per quality-adjusted life-year (QALY) gained with dalteparin
      for 10 or 35 days relative to 10 days of warfarin. STUDY PERSPECTIVE: Canadian
      provincial healthcare system. MAIN OUTCOME MEASURES AND RESULTS: The cost per
      QALY gained with 10 days of dalteparin was below $Can1000 for all the surgeries
      evaluated (all costs are reported in 2007 Canadian dollars [$Can1 = $US1, as of
      December 2007]). In the case of extended prophylaxis, the incremental cost per
      QALY gained with 35 days of dalteparin over warfarin was $Can40 100, $Can46 500,
      and $Can31 200 for patients undergoing THR, TKR, and HFS, respectively. Reducing
      the duration of prophylaxis from 35 to 28 days generated ratios that were below
      $Can35 000 for all three surgeries evaluated. CONCLUSION: Ten days of dalteparin
      following major orthopedic surgery is a clinically and economically attractive
      alternative to warfarin for DVT prophylaxis. In the case of the 35-day dalteparin
      protocol, the results also indicated acceptable economic value to a publicly
      funded healthcare system, particularly in the settings of HFS and THR. In
      addition, reducing the duration of prophylaxis to 28 days postsurgery would be
      associated with a more favorable return on public healthcare expenditures.

PMID- 19178132
TI  - Coadministration of dabigatran etexilate and atorvastatin: assessment of
      potential impact on pharmacokinetics and pharmacodynamics.
AB  - BACKGROUND: Dabigatran etexilate, a novel oral direct thrombin inhibitor, has
      been approved for prophylaxis of thromboembolism in patients undergoing total
      knee or total hip replacement, and is under clinical investigation for treatment
      of venous thromboembolism, prevention of stroke in patients with atrial
      fibrillation, and the treatment of thromboembolic complications following acute
      coronary syndromes. OBJECTIVE: To evaluate the potential impact of atorvastatin
      coadministration on the pharmacokinetics, pharmacodynamics, and safety of
      dabigatran etexilate. METHODS: Healthy male and female volunteers (n = 22) were
      recruited to this open, randomized, multiple-dose, three-way crossover study.
      They received dabigatran etexilate 150 mg twice daily on days 1-3 and once daily
      on day 4, atorvastatin 80 mg once daily on days 1-4, or both treatments together
      on days 1-4. RESULTS: Exposure to dabigatran at steady state (area under the drug
      plasma concentration-time curve at steady state) was reduced by 18% with
      concomitant atorvastatin administration. An 18% increase in plasma atorvastatin
      concentration occurred with coadministration of dabigatran etexilate. Exposure to
      its metabolite 2'-hydroxy-atorvastatin remained essentially unchanged and
      exposure to 4'-hydroxy-atorvastatin was increased by 15%. The small changes
      observed are deemed of little clinical relevance given the overall inter
      individual variability in the metabolism of atorvastatin. Furthermore, there were
      no changes in the concentrations of active HMG-CoA reductase inhibitors in plasma
      following dabigatran etexilate coadministration. Six subjects in the atorvastatin
      treatment group, six subjects during combination treatment, and eight subjects in
      the dabigatran treatment group reported adverse events. Most of the adverse
      events reported were nervous system disorders such as dizziness and headache, and
      general disorders such as fatigue. All adverse events were resolved at the end of
      the study. CONCLUSION: Results of this randomized, open-label, three-way
      crossover design study in healthy male and female volunteers showed that
      atorvastatin had no influence on the pharmacokinetic/pharmacodynamic profile of
      dabigatran, and vice versa, dabigatran etexilate had no impact on the
      pharmacokinetic/pharmacodynamic profile of atorvastatin. Both drugs were well
      tolerated when given alone or in combination.

PMID- 19178134
TI  - Molecular features of neonicotinoid pharmacophore variants interacting with the
      insect nicotinic receptor.
AB  - Molecular interactions of neonicotinoid insecticides with the nicotinic
      acetylcholine receptor have been mapped by chemical and structural neurobiology
      approaches, thereby encouraging the biorational design of novel nicotinic
      ligands. This investigation designs, prepares, and evaluates the target site
      potency of neonicotinoid analogues with various types of electronegative
      pharmacophores and subsequently predicts their molecular recognition in the
      ligand-binding pocket. The N-nitroimino (NNO2) neonicotinoid pharmacophore is
      systematically replaced by N-nitrosoimino (NNO), N-formylimino [NC(O)H], N-alkyl-
      and N-arylcarbonylimino [NC(O)R], and N-alkoxy- and N-aryloxycarbonylimino
      [NC(O)OR] variants. The NNO analogues essentially retain the binding affinity of
      the NNO2 compounds, while the isosteric NC(O)H congeners have diminished potency.
      The NC(O)R and NC(O)OR analogues, where R is methyl, trifluoromethyl, phenyl, or
      pyridin-3-yl, have moderate to high affinities. Orientation of the tip oxygen
      plays a critical role for binding of the NNO and NC(O)H pharmacophores, and the
      extended NC(O)R and NC(O)OR moieties are embraced by unique binding domains.

PMID- 19178136
TI  - Molecular mechanisms of MHC class I-antigen processing: redox considerations.
AB  - Major histocompatibility complex (MHC) class I molecules present antigenic
      peptides to the cell surface for screening by CD8(+) T cells. A number of ER
      resident chaperones assist the assembly of peptides onto MHC class I molecules, a
      process that can be divided into several steps. Early folding of the MHC class I
      heavy chain is followed by its association with beta(2)-microglobulin (beta(2)m).
      The MHC class I heavy chain-beta(2)m heterodimer is incorporated into the peptide
      loading complex, leading to peptide loading, release of the peptide-filled MHC
      class I molecules from the peptide-loading complex, and exit of the complete MHC
      class I complex from the ER. Because proper antigen presentation is vital for
      normal immune responses, the assembly of MHC class I molecules requires tight
      regulation. Emerging evidence indicates that thiol-based redox regulation plays
      critical roles in MHC class I-restricted antigen processing and presentation,
      establishing an unexpected link between redox biology and antigen processing. We
      review the influences of redox regulation on antigen processing and presentation.
      Because redox signaling pathways are a rich source of validated drug targets,
      newly discovered redox biology-mediated mechanisms of antigen processing may
      facilitate the development of more selective and therapeutic drugs or vaccines
      against immune diseases.

PMID- 19178137
TI  - Bottlenecks and hubs in inferred networks are important for virulence in
      Salmonella typhimurium.
AB  - Recent advances in experimental methods have provided sufficient data to consider
      systems as large networks of interconnected components. High-throughput
      determination of protein-protein interaction networks has led to the observation
      that topological bottlenecks, proteins defined by high centrality in the network,
      are enriched in proteins with systems-level phenotypes such as essentiality.
      Global transcriptional profiling by microarray analysis has been used extensively
      to characterize systems, for example, examining cellular response to
      environmental conditions and effects of genetic mutations. These transcriptomic
      datasets have been used to infer regulatory and functional relationship networks
      based on co-regulation. We use the context likelihood of relatedness (CLR) method
      to infer networks from two datasets gathered from the pathogen Salmonella
      typhimurium: one under a range of environmental culture conditions and the other
      from deletions of 15 regulators found to be essential in virulence. Bottleneck
      and hub genes were identified from these inferred networks, and we show for the
      first time that these genes are significantly more likely to be essential for
      virulence than their non-bottleneck or non-hub counterparts. Networks generated
      using simple similarity metrics (correlation and mutual information) did not
      display this behavior. Overall, this study demonstrates that topology of networks
      inferred from global transcriptional profiles provides information about the
      systems-level roles of bottleneck genes. Analysis of the differences between the
      two CLR-derived networks suggests that the bottleneck nodes are either mediators
      of transitions between system states or sentinels that reflect the dynamics of
      these transitions.

PMID- 19178138
TI  - Thermodynamic data for olefin and acetylene complexes of transition metals.

PMID- 19178139
TI  - Topological signatures of species interactions in metabolic networks.
AB  - The topology of metabolic networks can provide insight not only into the
      metabolic processes that occur within each species, but also into interactions
      between different species. Here, we introduce a novel pair-wise, topology-based
      measure of biosynthetic support, reflecting the extent to which the nutritional
      requirements of one species could be satisfied by the biosynthetic capacity of
      another. To evaluate the biosynthetic support for a given pair of species, we use
      a graph-based algorithm to identify the set of exogenously acquired compounds in
      the metabolic network of the first species, and calculate the fraction of this
      set that occurs in the metabolic network of the second species. Reconstructing
      the metabolic network of 569 bacterial species and several eukaryotes, and
      calculating the biosynthetic support score for all bacterial-eukaryotic pairs, we
      show that this measure indeed reflects host-parasite interactions and facilitates
      a successful prediction of such interactions on a large-scale. Integrating this
      method with phylogenetic analysis and calculating the biosynthetic support of
      ancestral species in the Firmicutes division (as well as other bacterial
      divisions) further reveals a large-scale evolutionary trend of biosynthetic
      capacity loss in parasites. The inference of ecological features from genomic
      based data presented here lays the foundations for an exciting "reverse ecology"
      framework for studying the complex web of interactions characterizing various
      ecosystems.

PMID- 19178140
TI  - Reverse engineering molecular regulatory networks from microarray data with qp
      graphs.
AB  - Reverse engineering bioinformatic procedures applied to high-throughput
      experimental data have become instrumental in generating new hypotheses about
      molecular regulatory mechanisms. This has been particularly the case for gene
      expression microarray data, where a large number of statistical and computational
      methodologies have been developed in order to assist in building network models
      of transcriptional regulation. A major challenge faced by every different
      procedure is that the number of available samples n for estimating the network
      model is much smaller than the number of genes p forming the system under study.
      This compromises many of the assumptions on which the statistics of the methods
      rely, often leading to unstable performance figures. In this work, we apply a
      recently developed novel methodology based in the so-called q-order limited
      partial correlation graphs, qp-graphs, which is specifically tailored towards
      molecular network discovery from microarray expression data with p >> n. Using
      experimental and functional annotation data from Escherichia coli, here we show
      how qp-graphs yield more stable performance figures than other state-of-the-art
      methods when the ratio of genes to experiments exceeds one order of magnitude.
      More importantly, we also show that the better performance of the qp-graph method
      on such a gene-to-sample ratio has a decisive impact on the functional coherence
      of the reverse-engineered transcriptional regulatory modules and becomes crucial
      in such a challenging situation in order to enable the discovery of a network of
      reasonable confidence that includes a substantial number of genes relevant to the
      essayed conditions. An R package, called qpgraph implementing this method is part
      of the Bioconductor project and can be downloaded from (www.bioconductor.org). A
      parallel standalone version for the most computationally expensive calculations
      is available from (http://functionalgenomics.upf.xsedu/qpgraph).

PMID- 19178141
TI  - Stability of medium-bridged twisted amides in aqueous solutions.
AB  - "Twisted" amides containing nonstandard dihedral angles are typically
      hypersensitive to hydrolysis, a feature that has stringently limited their
      utility in water. We have synthesized a series of bridged lactams that contain a
      twisted amide linkage but exhibit enhanced stability in aqueous environments.
      Many of these compounds were extracted unchanged from aqueous mixtures ranging
      from the strongly basic to the strongly acidic. NMR experiments showed that
      tricyclic lactams undergo reversible hydrolysis at extreme pH ranges but that a
      number of compounds in this structure class are indefinitely stable under
      physiologically relevant pH conditions; one bicyclic example was additionally
      water-soluble. We examined the effect of structure on the reversibility of amide
      bond hydrolysis, which we attributed to the transannular nature of the amino acid
      analogs. These data suggest that medium-bridged lactams of these types should
      provide useful platforms for studying the behavior of twisted amides in aqueous
      systems.

PMID- 19178142
TI  - Observation of beta-sheet aggregation in a gas-phase tau-peptide dimer.
AB  - In Alzheimer's disease, the tau protein forms intracellular amyloid fibrils in
      which the (306)VQIVYK(311) sequence adopts parallel beta-sheets, enabling fibril
      formation via cross-beta "steric zippers". We investigated aggregation of the
      protected segment (Ac-VQIVYK-NHMe) using IR/UV hole-burning spectroscopy in the
      NH stretch region in a cold molecular beam combined with DFT calculations in
      order to characterize its structure and identify the noncovalent interactions
      generally responsible for aggregation and stabilization in amyloid peptides. The
      computed and experimental IR spectra suggest that the tau-protein fragments form
      extended beta-strands that are combined in a beta-sheet through characteristic
      backbone hydrogen bonds, indicating that this secondary structure is
      energetically most attractive and readily forms in the gas phase, without any
      "guiding" interactions from a solvent or protein environment.

PMID- 19178143
TI  - Salicylaldehyde azines as fluorophores of aggregation-induced emission
      enhancement characteristics.
AB  - A series of salicylaldehyde azine derivatives were found to exhibit interesting
      aggregation-induced emission enhancement (AIEE) characteristics. In good solvent,
      all these compounds displayed very weak fluorescence, while strong emission was
      observed when they were placed in poor solvent. Moreover, the AIEE color of these
      compounds varied from green to red depending on the substituents on azines. Their
      in situ formation also promises potential applications in fluorescence sensing of
      hydrazine.

PMID- 19178144
TI  - Target specific intracellular delivery of siRNA/PEI-HA complex by receptor
      mediated endocytosis.
AB  - Hyaluronic acid (HA) plays important biological roles in tissue integrity,
      angiogenesis, wound healing, and cell motility through the interaction with
      receptors on cell membranes. In this work, we investigated the effect of HA
      modification on the receptor-mediated endocytosis labeling HA derivatives with
      quantum dots (QDots). HA-QDot conjugates with a degree of modification less than
      ca. 25 mol % appeared to be more efficiently taken up to B16F1 cells by HA
      receptor mediated endocytosis than QDots alone. On the basis of bioimaging study,
      polyethyleneimine, PEI-HA conjugate with 24.2 mol % PEI content was developed as
      a target specific intracellular delivery carrier of siRNA. The siRNA/PEI-HA
      complex exhibited higher gene silencing efficiency in B16F1 cells with HA
      receptors than siRNA/PEI complex. Anti-PGL3-Luc siRNA/PEI-HA complex appeared to
      silence PGL3-Luc gene in the range of 50%-85% depending on the serum
      concentration up to 50 vol %. According to in vivo biodistribution test,
      siRNA/PEI-HA complex accumulated mainly in the tissues with HA receptors such as
      liver, kidney, and tumor. Furthermore, intratumoral injection of anti-VEGF
      siRNA/PEI-HA complex resulted in an effective inhibition of tumor growth by the
      HA receptor mediated endocytosis to tumor cells in C57BL/6 mice. Considering all
      these results, anti-VEGF siRNA/PEI-HA complex was thought to be applied
      successfully as target specific antiangiogenic therapeutics for the treatment of
      diseases in the tissues with HA receptors, such as liver cancer and kidney
      cancer.

PMID- 19178145
TI  - Charge screening in the S(N)2 reaction of charged electrophiles and charged
      nucleophiles: an ionic liquid effect.
AB  - The application of liquids that are salts at room temperature to chemical
      synthesis has become a hugely exciting field of study. The greatest promise that
      these ionic liquids hold is that they might offer process advantages, even novel
      behaviors that cannot be achieved in molecular solvents. We report here that the
      S(N)2 reaction of the trifluoromethanesulfonate and
      bis(trifluoromethanesulfonyl)imide salts of dimethyl-4-nitrophenylsulfonium ([p
      NO(2)PhS(CH(3))(2)](+)[X](-); [X](-) = [CF(3)SO(3)](-), [N(CF(3)SO(2))(2)](-))
      with chloride ion follow a fundamentally different pathway to when the same salts
      react in molecular solvents.

PMID- 19178146
TI  - A systematic CCSD(T) study of long-range and noncovalent interactions between
      benzene and a series of first- and second-row hydrides and rare gas atoms.
AB  - Binding energies, potential energy curves, and equilibrium intermonomer distances
      describing the interaction between benzene and a series of first- and second-row
      hydrides and rare gas atoms are calculated using coupled-cluster theory with
      single, double, and perturbative triple excitations (CCSD(T)) in conjunction with
      a large augmented quadruple-zeta basis set (aug-cc-pVQZ). These benchmark results
      are accurate to within one eighth of 1 kcal/mol and, as such, provide a reliable
      foundation for the development and testing of more approximate methods for
      calculating long-range and noncovalent interactions.

PMID- 19178147
TI  - Metal-phosphorus bonding in complexes W@Au12PX3 (X = H, F, Cl, Br, I, Me, OMe)
      and [M@Au12](q)PH3 (M(q) = Hf2-, Ta-, W, Re+, Os2+, Ir3+, Pt4+, Au5+):
      relativistic DFT investigations.
AB  - Relativistic density functional theory (DFT) calculations of the geometries and
      Au-P bonding of W@Au(12)PX(3) (X = H, F, Cl, Br, I, Me, OMe) and
      [M@Au(12)](q)PH(3) (M(q) = Hf(2-), Ta(-), W, Re(+), Os(2+), Ir(3+), Pt(4+),
      Au(5+)) have been carried out. There are some regular changes in geometry and
      binding of these two kinds of complexes with the variation of the phosphanes
      PX(3) and transition metals M(q). The energy decomposition analysis confirms that
      the PX(3) ligands are sigma donors. The donor tendency (DeltaE(sigma)/DeltaE(pi))
      decreases for different X with increasing electronegativity and for different
      M(q) from Au(5+) to Hf(2-), while the pi-back-donation increases in the same
      direction. The calculated P-H bond lengths show a regular decrease from Hf(2-) to
      Ir(3+), but have abnormal trends for Pt(4+) and Au(5+).

PMID- 19178148
TI  - Mass selection of ions from beams using waveform isolation in radiofrequency
      quadrupoles.
AB  - A waveform isolation method is described for the mass-selective transmission of
      ions through quadrupole mass filters, and it is implemented on a new tandem mass
      analyzer instrument. The method features the application of broad-band waveforms
      comprising appropriate frequencies to cause mass-selective instability in ions of
      particular mass-to-charge (m/z) and to transmit all others. The experiment is
      implemented in a tandem quadrupole system in which the first mass filter is a
      rectilinear ion trap (RIT) operated in a continuous mass-selective mode to
      transmit ions of ions of one or more arbitrarily selected m/z value(s). The
      second analyzer was used to verify the quality of the mass selection achieved
      using the first analyzer via conventional quadrupole ion trap mass-selective
      instability scanning. A new subtype of product ion tandem mass spectrometry
      (MS/MS) scan, termed the summed product ion scan, is demonstrated with a mixture
      of biological compounds. It is used to characterize product ions arising after
      simultaneous isolation and collisional activation of multiple precursor species,
      in this case ions of the same analyte generated in different charge states. The
      summed product ion scan can be useful for enhancing sensitivity for the analyte
      of interest or for providing more comprehensive information about an analyte than
      is available by monitoring a single ionized form of the analyte. The analytical
      performance of the waveform isolation method is tested using simple drug
      mixtures, and its potential for increasing overall yields in preparative mass
      spectrometry is explored briefly. It is shown that efficiencies of ca. 70% of ion
      transfer to a surface for ion soft landing surface can be achieved. The upper
      mass range is limited by axial acceleration arising from the stretched geometry,
      and one solution to this problem is provided.

PMID- 19178149
TI  - Effective determination of the long-lived nuclide 41Ca in nuclear reactor
      bioshield concretes: comparison of liquid scintillation counting and accelerator
      mass spectrometry.
AB  - The routine application of liquid scintillation counting to (41)Ca determination
      has been hindered by the absence of traceable calibration standards of known
      (41)Ca activity concentrations. The introduction of the new IRMM (41)Ca mass
      spectrometric standards with sufficiently high (41)Ca activities for radiometric
      detection has partly overcome this although accurate measurement of stable Ca
      concentrations coupled with precise half-life data are still required to correct
      the certified (41)Ca:(40)Ca ratios to (41)Ca activity concentrations. In this
      study, (41)Ca efficiency versus quench curves have been produced using the IRMM
      standard, and their accuracy validated by comparison with theoretical
      calculations of (41)Ca efficiencies. Further verification of the technique was
      achieved through the analysis of (41)Ca in a reactor bioshield core that had been
      previously investigated for other radionuclide variations. Calcium-41 activity
      concentrations of up to 25 Bq/g were detected. Accelerator mass spectrometry
      (AMS) measurements of the same suite of samples showed a very good agreement,
      providing validation of the procedure. Calcium-41 activity concentrations
      declined exponentially with distance from the core of the nuclear reactor and
      correlated well with the predicted neutron flux.

PMID- 19178150
TI  - Characterization of a heparin-binding site on the catalytic domain of factor XIa:
      mechanism of heparin acceleration of factor XIa inhibition by the serpins
      antithrombin and C1-inhibitor.
AB  - Heparin accelerates inhibition of factor XIa (fXIa) by the serpins antithrombin
      (AT) and C1-inhibitor (C1-INH) by more than 2 orders of magnitude. The mechanism
      of the heparin-mediated acceleration of fXIa inhibition by these serpins is
      incompletely understood, as heparin appears to interact with both the catalytic
      and noncatalytic domains of the protease. We replaced the basic residues of the
      fXIa 170 loop (Lys-170, Arg-171, Arg-173, Lys-175, and Lys-179; chymotrypsin
      numbering) with Ala, using an expression system that allows separation of the
      fXIa catalytic domain (CD) from noncatalytic domains. Heparin-mediated inhibition
      of 170 loop CD variants with AT was impaired 3-10-fold relative to that of the
      wild-type (CD-WT). In reactions with C1-INH, Arg-171 was the most critical
      residue contributing approximately 2-3-fold to heparin-mediated inhibition of CD
      WT. A template mechanism did not fully account for the effect of heparin with
      either serpin, as the second-order inhibition rate constants did not exhibit a
      characteristic bell-shaped dependence on heparin concentration. Further studies
      revealed that the C1-INH inhibition of full-length fXIa containing Ala
      substitutions for basic residues of the 148 loop is not enhanced by heparin.
      Inhibition by AT of a full-length fXIa variant containing an Ala substitution for
      Arg-37 in the fXIa CD was approximately 5-fold greater than for wild-type fXIa in
      the absence of heparin. These results suggest that basic residues of the fXIa 170
      loop form a heparin-binding site and that the accelerating effect of heparin on
      inhibition of fXIa by AT or C1-INH may be mediated by charge neutralization
      and/or allosteric mechanisms that overcome the repulsive inhibitory interactions
      of serpins with basic residues on the fXIa 148 and 37 loops.

PMID- 19178152
TI  - Probing the heme-binding site of the cytochrome c maturation protein CcmE.
AB  - Maturation of c-type cytochromes in many bacterial species and plant mitochondria
      requires the participation of the heme chaperone CcmE that binds heme covalently
      via a His residue (H130 in Escherichia coli) before transferring it
      stereospecifically to the apo form of cytochromes c. Only the structure of the
      apo form of CcmE is known; the heme-binding site has been modeled on the surface
      of the protein in the vicinity of H130. We have determined the reduction
      potential of CcmE, which suggests that heme bound to CcmE is not as exposed to
      solvent as was initially thought. Alanine insertions in the vicinity of the heme
      binding histidine (which we showed by NMR do not perturb the protein fold)
      strikingly abolish formation of both holo-CcmE and cytochrome c, whereas
      previously reported point mutations of residues adjacent to H130 gave only a
      partial attenuation. The heme iron coordinating residue Y134 proved to be
      strictly required for axial ligation of both ferrous and ferric heme. These
      results indicate the existence of a conformationally well-defined heme pocket
      that involves amino acids located in the proximity of H130. However, mutation of
      Y134 affected neither heme attachment to CcmE nor cytochrome c maturation,
      suggesting that heme binding and release from CcmE are hydrophobically driven and
      relatively indifferent to axial ligation.

PMID- 19178151
TI  - A catalytic metal ion interacts with the cleavage Site G.U wobble in the HDV
      ribozyme.
AB  - The HDV ribozyme self-cleaves by a chemical mechanism involving general acid-base
      catalysis to generate 2',3'-cyclic phosphate and 5'-hydroxyl termini. Biochemical
      studies from several laboratories have implicated C75 as the general acid and
      hydrated magnesium as the general base. We have previously shown that C75 has a
      pK(a) shifted >2 pH units toward neutrality [Gong, B., Chen, J. H., Chase, E.,
      Chadalavada, D. M., Yajima, R., Golden, B. L., Bevilacqua, P. C., and Carey, P.
      R. (2007) J. Am. Chem. Soc. 129, 13335-13342], while in crystal structures, it is
      well-positioned for proton transfer. However, no evidence for a hydrated
      magnesium poised to serve as a general base in the reaction has been observed in
      high-resolution crystal structures of various reaction states and mutants.
      Herein, we use solution kinetic experiments and parallel Raman crystallographic
      studies to examine the effects of pH on the rate and Mg(2+) binding properties of
      wild-type and 7-deazaguanosine mutants of the HDV ribozyme. These data suggest
      that a previously unobserved hydrated magnesium ion interacts with N7 of the
      cleavage site G.U wobble base pair. Integrating this metal ion binding site with
      the available crystal structures provides a new three-dimensional model for the
      active site of the ribozyme that accommodates all available biochemical data and
      appears competent for catalysis. The position of this metal is consistent with a
      role of a magnesium-bound hydroxide as a general base as dictated by biochemical
      data.

PMID- 19178153
TI  - Potent inhibitors of HIV-1 integrase display a two-step, slow-binding inhibition
      mechanism which is absent in a drug-resistant T66I/M154I mutant.
AB  - Two-metal binding HIV-1 integrase inhibitors (INIs) are potent inhibitors of HIV
      1 in vitro and in patients. We report here for the first time the kinetics of
      inhibition of integrase-catalyzed strand transfer. First, the IC(50) values for
      each of six structurally distinct INIs decreased when a preincubation was
      included: S-1360 (1.3 microM vs 0.12 microM), L-731,988 (130 nM vs 9 nM), L
      870,810 (130 nM vs 4 nM), raltegravir (300 nM vs 9 nM), elvitegravir (90 nM vs 6
      nM), and GSK364735 (90 nM vs 6 nM). When reactions with these INIs were initiated
      with integrase, progress curve analyses indicated time-dependent inhibition,
      which could be fitted to a two-step mechanism of binding. Overall fitted K(i)
      values matched the IC(50) values measured with a preincubation: S-1360 (0.17
      microM), L-731,988 (34 nM), L-870,810 (2.4 nM), raltegravir (10 nM), elvitegravir
      (4.0 nM), and GSK364735 (2.5 nM). To begin to understand the mechanism for this
      slow onset of inhibition and its possible impact on drug resistance, studies of
      resistance mutations were initiated. T66I/M154I exhibited little if any time
      dependent inhibition by any of the six INIs, as measured by differences in
      potency upon preincubation or by progress curve analysis. These data demonstrate
      that slow binding is a signature of two-metal binding INIs, and that the second
      slow step is required for full potency. We discuss a possible structural
      explanation of the second slow step of inhibition and also the relationship
      between loss of time-dependent inhibition and drug resistance of this important
      new class of HIV-1 antiretroviral drugs.

PMID- 19178154
TI  - Structural domains and main-chain flexibility in prion proteins.
AB  - In this study we describe a novel approach to define structural domains and to
      characterize the local flexibility in both human and chicken prion proteins. The
      approach we use is based on a comprehensive theory of collective dynamics in
      proteins that was recently developed. This method determines the essential
      collective coordinates, which can be found from molecular dynamics trajectories
      via principal component analysis. Under this particular framework, we are able to
      identify the domains where atoms move coherently while at the same time to
      determine the local main-chain flexibility for each residue. We have verified
      this approach by comparing our results for the predicted dynamic domain systems
      with the computed main-chain flexibility profiles and the NMR-derived random coil
      indexes for human and chicken prion proteins. The three sets of data show
      excellent agreement. Additionally, we demonstrate that the dynamic domains
      calculated in this fashion provide a highly sensitive measure of protein
      collective structure and dynamics. Furthermore, such an analysis is capable of
      revealing structural and dynamic properties of proteins that are inaccessible to
      the conventional assessment of secondary structure. Using the collective dynamic
      simulation approach described here along with a high-temperature simulations of
      unfolding of human prion protein, we have explored whether locations of
      relatively low stability could be identified where the unfolding process could
      potentially be facilitated. According to our analysis, the locations of
      relatively low stability may be associated with the beta-sheet formed by strands
      S1 and S2 and the adjacent loops, whereas helix HC appears to be a relatively
      stable part of the protein. We suggest that this kind of structural analysis may
      provide a useful background for a more quantitative assessment of potential
      routes of spontaneous misfolding in prion proteins.

PMID- 19178155
TI  - Proton release group of pharaonis phoborhodopsin revealed by ATR-FTIR
      spectroscopy.
AB  - The proton release mechanism has been one of the recent interesting topics in the
      field of microbial rhodopsins since it was established that a protonated water
      cluster is the proton release group(PRG) in bacteriorhodopsin (BR). pharaonis
      phoborhodopsin [ppR, also called pharaonis sensory rhodopsinII (pSRII)] is a
      photoreceptor for negative phototaxis in Natronomonas pharaonis, and in the
      absence of transducer protein, pHtrII, ppR can pump protons like BR. Fast, BR
      like proton release was observed during the lifetime of the M intermediate (ppRM)
      at low pH, but it was slowed in the absence of Cl-[Iwamoto, M., et al. (2004)
      Biochemistry 43, 3195]. This observation suggests that Cl- binding controls the
      pKa of PRG in ppR and ppRM. In this paper, we studied the molecular mechanism of
      the PRG action in ppR by means of Cl(-)-induced and light-induced difference
      attenuated total reflection (ATR) FTIRspectroscopy in the aqueous phase. Cl(-)
      induced difference ATR-FTIR spectra clearly demonstrated that binding of Cl- to
      ppR accompanies protonation of a carboxylic acid (C=O stretch at 1724 cm-1). The
      amino acid was identified as Asp193, because the corresponding band is shifted to
      1705 cm-1 in the D193Emutant protein. Light-induced ppRM minus ppR difference ATR
      FTIR spectra show the deprotonation signal of Asp193 (at 1724 cm-1) only in the
      presence of Cl-. The double-difference spectrum between the light-induced changes
      in the presence and absence of Cl- is a mirror image of the spectrum of Cl
      binding in the dark, indicating that ppRM formation accompanies deprotonation of
      Asp193 and dissociation of Cl- simultaneously. It was also shown that structural
      changes of arginine are involved in these processes by use of [15N]arginine
      labeled ppR. We thus conclude that the PRG of ppR includes Asp193, whose pKa
      changes are controlled by Cl- and Arg72.

PMID- 19178156
TI  - Forces and transport velocities for a particle in a slot waveguide.
AB  - Optofluidic transport seeks to exploit the high-intensity electromagnetic energy
      in waveguiding structures to manipulate nanoscopic matter using radiation
      pressure and optical trapping forces. In this paper, we present an analysis of
      optical trapping and transport of sub-100 nm polystyrene and gold nanoparticles
      in silicon slot waveguides. This study focuses on the effect of particle size,
      particle refractive index, and slot waveguide geometry on trapping stability and
      the resulting transport speed. Our results indicate that stable trapping and
      transport can be achieved for objects as small as 10 or 20 nm in diameter with as
      much as a 100 fold enhancement in trapping stiffness over the state of the art.

PMID- 19178157
TI  - Weak Bronsted acid-thiourea co-catalysis: enantioselective, catalytic protio
      Pictet-Spengler reactions.
AB  - The development of one-pot imine formation and asymmetric Pictet-Spengler
      reactions cocatalyzed by a chiral thiourea and benzoic acid is described.
      Optically active tetrahydro-beta-carbolines, ubiquitous structural motifs in
      biologically active natural products, are obtained in high ee directly from
      tryptamine and aldehyde precursors.

PMID- 19178158
TI  - Alpha-glycosphingolipids via chelation-induced anomerization of O- and S
      glucuronic and galacturonic acid derivatives.
AB  - Bacterial glycolipids containing either alpha-glucuronic acid or alpha
      galacturonic acid residues have an important role in the innate-type immune
      response to gram-negative bacteria. Synthesis of closely related compounds,
      including a novel alpha-SO(2) glycolipid mimetic, is described from carbohydrate
      precursors where anomerization is a key step. Very high stereoselectivites (>97:3
      in favor of alpha) were observed from O-glycoside precursors.

PMID- 19178159
TI  - Indolynes as electrophilic indole surrogates: fundamental reactivity and
      synthetic applications.
AB  - A mild method to access a variety of substituted indole derivatives has been
      developed. The strategy relies on the generation of highly reactive indolyne
      intermediates, which function as electrophilic indole surrogates.

PMID- 19178160
TI  - A general method for the synthesis of unsymmetrically substituted ureas via
      palladium-catalyzed amidation.
AB  - A general and practical method for the preparation of unsymmetrically substituted
      ureas has been developed utilizing palladium-catalyzed amidation. Both aryl
      bromides and chlorides, as well as heteroaryl chlorides, have been coupled to
      aryl, benzyl, and aliphatic ureas by using a novel nonproprietary bipyrazole
      ligand (bippyphos).

PMID- 19178161
TI  - Ionic liquid-supported (ILS) (S)-pyrrolidine sulfonamide, a recyclable
      organocatalyst for the highly enantioselective Michael addition to nitroolefins.
AB  - A new class of ionic liquid supported (ILS) (S)-pyrrolidine sulfonamide
      organocatalyst has been developed and shown to be a very effective catalyst for
      the asymmetric Michael addition reactions of ketones and aldehyde to nitroolefins
      with high enantio- and diastereoselectivities. This ILS organocatalyst is also
      easily recycled and could be reused at least five times without significant loss
      of its ability to affect the outcome of the asymmetric reactions.

PMID- 19178162
TI  - Bioactive sulfated sesterterpene alkaloids and sesterterpene sulfates from the
      marine sponge Fasciospongia sp.
AB  - Two new sulfated sesterterpene alkaloids, 19-oxofasciospongine A (3) and
      fasciospongine C (4), and a new sesterterpene sulfate, 25-hydroxyhalisulfate 9
      (5), along with two known sesterterpene sulfates, halisulfates 7 (6) and 9 (7),
      were isolated from an organic extract of the marine sponge Fasciospongia sp. The
      structures of the new compounds were established on the basis of one- and two
      dimensional NMR spectroscopic studies as well as by HRESIMS analysis. Compounds 1
      7 exhibited inhibitory activity against Streptomyces 85E in the hyphae-formation
      inhibition assay. Compounds 1, 2, and 4-7 were not cytotoxic when tested at 20
      microg/mL with MCF-7, LNCaP, and LU cell lines. Only compound 3 demonstrated a
      moderate cytotoxic effect on the MCF-7 (IC(50) 13.4 microM), LNCaP (IC(50) 21.8
      microM), and LU-1 cells (IC(50) 5.0 microM), respectively.

PMID- 19178163
TI  - Atomistic simulation combined with analytic theory to study the response of the P
      selectin/PSGL-1 complex to an external force.
AB  - Steered molecular dynamics simulations are combined with analytic theory in order
      to gain insights into the properties of the P-selectin/PSGL-1 catch-slip bond at
      the atomistic level of detail. The simulations allow us to monitor the
      conformational changes in the P-selectin/PSGL-1 complex in response to an
      external force, while the theory provides a unified framework bridging the
      simulation data with experiment over 9 orders of magnitude. The theory predicts
      that the probability of bond dissociation by the catch mechanism is extremely low
      in the simulations; however, a few or even a single trajectory can be sufficient
      for characterization of the slip mechanism. Theoretical analysis of the
      simulation data shows that the bond responds to the force in a highly nonlinear
      way, with the bond stiffness changing considerably as a function of the force
      ramp rate. The Langevin description of the simulation provides spring constants
      of the proteins and the binding interaction and gives the friction coefficient
      associated with the receptor-ligand motion in water. The estimated relaxation
      time shows that the simple probabilistic description is accurate for the
      experimental regime and remains approximately valid for the high ramp rates used
      in simulations. The simulations establish that bond deformation occurs primarily
      within the P-selectin receptor region. The two interaction sites within the
      binding pocket dissociate sequentially, raising the possibility of observing
      these independent rupture events in experiment. The stronger interaction that
      determines the overall properties of the bond dissociates first, indicating that
      the experimental data indeed capture the main rupture event and not the secondary
      weaker site rupture. The main rupture event involves the interaction between the
      calcium ion of the receptor and the ligand residue FUC-623. It is followed by new
      interactions, supporting the sliding-rebinding behavior observed in the earlier
      simulation [ Lou, J. Zhu, C. Biophys. J. 2007 , 92 , 1471 - 1485 ]. The weaker
      binding site shows fewer interaction features, suggesting that the sliding
      rebinding behavior may be determined by the unique properties of the calcium
      site. The agreement between simulation and experiment provided by the two-pathway
      and deformation models, each containing only four parameters, indicates that the
      essential physics of the catch-slip bond should be relatively simple and robust
      over a wide range of pulling regimes.

PMID- 19178164
TI  - Weak epitaxy growth of copper hexadecafluorophthalocyanine (F16CuPc) on p
      sexiphenyl monolayer film.
AB  - Weak epitaxy growth (WEG) behavior and mechanism of copper
      hexadecafluorophthalocyanine (F16CuPc) on p-sexiphenyl (p-6P) monolayer film were
      investigated by atomic force microscopy (AFM), selected area electron diffraction
      (SEAD), and wide-angle X-ray diffraction (WAXD). High-quality F16CuPc films with
      high order, large size, and molecular-level smoothness were obtained successfully
      by WEG method. It was identified that there exists incommensurate epitaxial
      relation between highly oriented F16CuPc and p-6P films. The geometrical channels
      of p-6P monolayer surface induce the nucleation and growth of F16CuPc molecules.
      Two kinds of in-plane structures, referred to as "phase I" and "phase II",
      coexist in the initial few molecular layers. As thin-film thickness increases,
      the distance of (001) plane diminishes and phase I disappears. Furthermore,
      coalescence, dislocation, and high-angle grain boundary between F16CuPc
      neighboring domains were observed by high-resolution AFM.

PMID- 19178166
TI  - Redox dependence of the reaction of alpha-alkoxyalkyl radicals with a series of
      oxidants.
AB  - Oxygen and oxidants enhance the sensitivity of cells to radiation. To understand
      this effect at the mechanistic level, the redox dependences for the reactivity of
      weakly reducing alpha-monoalkoxyalkyl radicals of 1,4-dioxane and tetrahydrofuran
      with a series of oxidants, for example, quinones, viologens, and nitro-arenes,
      with one-electron reduction potentials E71 values ranging from -80 to -640 mV,
      have been determined using the technique of pulse radiolysis. The second-order
      rate constants for these reactions with the alpha-monoalkoxyalkyl radicals of 1,4
      dioxane and tetrahydrofuran are in the range (0.03-1.5) x 109 and (1.0-6.6) x 109
      dm3 mol(-1) s(-1), respectively. The reactions of the alpha-alkoxyalkyl radicals
      of 1,4-dioxane with quinones and viologens involve an outer-sphere electron
      transfer, in contrast to a reaction with the nitro-arenes to give adducts. The
      resulting long-lived nitroaromatic adduct radicals were found to react with the
      reductant, TMPD, probably leading to the formation of hydroxylamine-type
      products. In cells, adducts formed on reaction of deoxyribose sugar radical with
      oxidants and subsequent reactions with reductants may contribute to the
      mechanisms involved in radiosensitization by oxygen and those oxidants that
      interact through adduct formation.

PMID- 19178167
TI  - Green decomposition of organic dyes using octahedral molecular sieve manganese
      oxide catalysts.
AB  - The catalytic degradation of organic dye (methylene blue, MB) has been studied
      using green oxidation methods (tertiary-butyl hydrogen peroxide, TBHP, as the
      oxidant with several doped mixed-valent and regular manganese oxide catalysts in
      water) at room and higher temperatures. These catalysts belong to a class of
      porous manganese oxides known as octahedral molecular sieves (OMS). The most
      active catalysts were those of Mo(6+)- and V(5+)-doped OMS. Rates of reaction
      were found to be first-order with respect to the dye. TBHP has been found to
      enhance the MB decomposition, whereas H(2)O(2) does not. Reactions were studied
      at pH 3-11. The optimum pH for these reactions was pH 3. Dye-decomposing activity
      was proportional to the amount of catalyst used, and a significant increase in
      catalytic activity was observed with increasing temperature. X-ray diffraction
      (XRD), energy dispersive spectroscopy (EDX), and thermogravimetric analysis (TGA)
      studies showed that no changes in the catalyst structure occurred after the dye
      degradation reaction. The products as analyzed by electrospray ionization mass
      spectrometry (ESI-MS) showed that MB was successively decomposed through
      different intermediate species.

PMID- 19178168
TI  - Endoscopic removal of a retained pelvic drain fragment with CO2 pneumoperitoneum.
AB  - Retained drains are an infrequent and usually avoidable postsurgical
      complication. There are few reports in the contemporary literature regarding
      minimally invasive techniques to remove retained postsurgical drains. We present
      a novel technique for the removal of a retained deep pelvic Jackson-Pratt drain
      by means of a fluoroscopically guided transurethral endoscopic technique with
      minimal CO(2) pneumoperitoneum performed safely through a newly transected
      urethral stump under local anesthesia. The use of CO(2) pneumoperitoneum in place
      of saline irrigation is less likely to be associated with any untoward
      postoperative complications. This novel and effective technique will serve as a
      useful adjunct to the minimally invasive management of retained pelvic drains in
      postoperative patients who have undergone cystectomy and/or hysterectomy.

PMID- 19178169
TI  - Laparoscopic cranial plication in pelviureteral junction obstruction by aberrant
      lower pole artery.
AB  - BACKGROUND AND PURPOSE: The standard management for pelviureteral junction (PUJ)
      obstruction is a laparoscopic dismembered pyeloplasty. We present the initial
      results of our experience of laparoscopic cranial transposition of lower-pole
      crossing vessels in the management of adult PUJ obstruction where crossing
      vessels were identified. PATIENTS AND METHODS: All patients during the last 2
      years who presented with PUJ obstruction caused by crossing lower-pole vessels
      underwent a laparoscopic transposition of the artery to a more cranial position
      and, in fact, plicated within the renal pelvis well above the PUJ to reduce the
      size of the baggy renal pelvis. Patients were followed up postoperatively with
      mercaptoacetyl triglycine renography as well as clinical symptom review at 3
      months, 6 months, and then yearly. RESULTS: Seven patients have undergone this
      procedure so far. The mean follow-up period at present is 14 months (range 8-22
      months). All patients had a nonobstructive renogram curve at 3 months and 6
      months. One patient has had renography at 22 months, which still shows a
      nonobstructive drainage pattern. All patients have had a resolution of their pain
      and urinary tract infections. The mean operative time, including the retrograde
      study and Double-J stent insertion was 121 minutes (range 110-131 min) with a
      mean blood loss of 30 mL. The mean hospital stay was 2 days. There were no
      complications. CONCLUSIONS: Although currently the number of patients is small
      and follow-up is short, this procedure appears to be effective in relieving both
      symptoms and obstruction in patients with lower-pole crossing vessels. Other
      benefits include shorter operative time, less blood loss, as well as no risk of
      anastomotic stricture and urine leak when compared with a dismembered
      pyeloplasty. The Double-J stent can be removed within a few days (typically 5 in
      our hands) or even shorter where logistically feasible. This reduces stent
      related complications.

PMID- 19178170
TI  - Percutaneous nephrolithotomy with ultrasonography-guided renal access in the
      lateral decubitus flank position.
AB  - PURPOSE: Our aim was to evaluate the safety and efficacy of percutaneous
      nephrolithotomy (PCNL) with ultrasonography (US)-guided renal access in the
      lateral decubitus flank position. PATIENTS AND METHODS: From July 2006 to March
      2008, 40 patients with renal stones > 2 cm underwent PCNL with US-guided renal
      access in the lateral decubitus flank position by a single surgeon. We report our
      technique and the outcomes in detail. RESULTS: Successful access was achieved in
      40 patients (100%). Complete stone clearance rate was 85% (34 patients). After
      surgery, six (15%) patients had stones (6-11 mm) detected by plain abdominal
      radiography or sonography and were referred for shockwave lithotripsy. The mean
      stone size was 29 mm (range 22-43 mm). The mean operative time was 45 minutes
      (range 32-75 min), and the mean hospital stay was 2.8 days (range 2-4 d).
      Postoperative US did not reveal considerable fluid collection. There were no
      visceral injuries. Also, there was no significant bleeding that led to
      transfusion intraoperatively and postoperatively. CONCLUSION: PCNL with US-guided
      renal access in the lateral decubitus flank position is safe and convenient, and
      prevents harmful effects of radiation for the surgeon, the surgical team, and the
      patient.

PMID- 19178171
TI  - The UCI Seldinger technique for percutaneous renal cryoablation: protecting the
      tract and achieving hemostasis.
AB  - PURPOSE: To describe our Seldinger technique of percutaneous renal cryoablation
      that was devised to facilitate renal biopsy, cryoprobe placement, and
      instillation of adjunctive hemostatics while protecting surrounding tissues from
      cryoinjury. PATIENTS AND METHODS: This approach was used to manage 13 renal
      masses in 12 adult patients. Under CT-fluoroscopic guidance, an access needle was
      inserted to abut the surface of the tumor, followed by an Amplatz super-stiff
      guidewire and a customized coaxial catheter system, which was used as a conduit
      for needle biopsy, cryoprobe insertion, and FloSeal instillation. In addition, a
      porcine model was used to compare the temperature readings adjacent to the
      sheathed and the unsheathed cryoprobe during percutaneous renal cryoablation.
      RESULTS: In all patients, the use of this access approach was accomplished
      without incident. Two patients needed blood transfusions. No patient had
      significant skin, muscle, or nerve debility. At a mean follow-up of 11 months,
      none had evidence of persistent disease on CT or MRI contrast imaging. In the
      porcine model, the customized sheath protected the surrounding tissues from
      reaching temperatures below 5 degrees C while temperatures down to -15 degrees C
      were obtained when no insulating sheath was used. CONCLUSIONS: A modified
      Seldinger technique enabled us to perform percutaneous renal cryotherapy through
      a single access channel, which facilitated access for biopsy, cryoprobe
      placement, and instillation of hemostatic agents. This approach may provide a
      protective barrier against cryogenic damage to neighboring tissues and could
      theoretically help minimize the chance of tract seeding.

PMID- 19178172
TI  - Long-term outcome of hand-assisted laparoscopic nephroureterectomy for pathologic
      T3 upper urinary tract urothelial carcinoma.
AB  - PURPOSE: To determine the feasibility and long-term outcomes of hand-assisted
      laparoscopic nephroureterectomy (HALNU) compared with open nephroureterectomy
      (ONU) in the management of pT(3)N0 upper urinary tract urothelial carcinoma (UUT
      UC). PATIENTS AND METHODS: Between January 1994 and December 2005, 21 patients
      who underwent HALNU for stage pT(3)N0 UTT-UC were matched and compared with 31
      patients who underwent ONU. The oncologic out-comes, including bladder
      recurrence, recurrence-free survival, cancer-specific survival, and overall
      survival, were statistically analyzed. RESULTS: The median follow-up period in
      the HALNU group was 72 months (range 33-111 months) and 115 months in the ONU
      group (range 24-161 months). Patient age, sex, body mass index, tumor size,
      specimen weight, and American Society of Anesthesiologists classification showed
      no significant difference between the two groups. The HALNU group had
      statistically less blood loss than the ONU group (113 mL versus 487 mL; P =
      0.02). The average hospital stay and doses of narcotic analgesics were
      significantly less in the HALNU group than the ONU group. The complication and
      bladder recurrence rates were similar between the two groups. The 5-year
      recurrence-free survival, cancer-specific survival, and overall survival were
      also comparable in both groups. CONCLUSIONS: HALNU is a safe and efficacious
      procedure with comparable long-term oncologic outcomes in comparison with ONU in
      treating patients with locally advanced pT(3)N0UUT-UC.

PMID- 19178173
TI  - Maximizing console surgeon independence during robot-assisted renal surgery by
      using the Fourth Arm and TilePro.
AB  - PURPOSE: We describe multiple uses of the fourth robotic arm and TilePro on the
      da Vinci S surgical system to maximize console surgeon independence from the
      assistant during robot-assisted renal surgery. MATERIALS AND METHODS: We
      prospectively evaluated the use of the fourth robotic arm and TilePro on the da
      Vinci S during robot-assisted radical nephrectomy (RRN) and robot-assisted
      partial nephrectomy (RPN). The fourth robotic arm was used to provide kidney
      retraction, place the renal hilum on stretch, control vascular structures, apply
      and remove bulldog clamps during partial nephrectomy, and secure renal capsular
      stitches. TilePro was used to project intraoperative ultrasonography and
      preoperative CT images onto the console screen. RESULTS: From January 2006 to
      June 2008, 90 robot-assisted kidney procedures were performed, of which the
      fourth robotic arm was used in 46 cases (RRN, 18; RPN, 24; nephroureterectomy,
      4). The fourth robotic arm facilitated consistent kidney retraction for
      dissection of the renal hilum and mobilization of the kidney. The robotic Hem-o
      Lok clip applier effectively controlled renal hilar vessels during eight RPN
      cases and secured renal capsular stitches during two RPN cases. Bulldog clamps
      were successfully applied to the renal artery during RPN using the fourth arm in
      two cases. TilePro was used during 22 RPN cases to project intraoperative
      ultrasonographic images and preoperative CT images onto the console screen as a
      picture-on-picture image to guide tumor resection. CONCLUSIONS: Robotic
      instruments used with the fourth robotic arm may give the console surgeon greater
      independence from the assistant during robot-assisted kidney surgery by
      facilitating steps such as kidney retraction, hilar dissection, and vascular
      control. The TilePro feature of the da Vinci S can be used to project
      intraoperative ultrasonography and preoperative imaging onto the console screen,
      potentially guiding tumor localization and resection during RPN without the need
      to leave the console to view external images.

PMID- 19178174
TI  - Apical margins after robot-assisted radical prostatectomy: does technique matter?
AB  - BACKGROUND AND PURPOSE: The apex is the most common site of an involved surgical
      margin after robot-assisted radical prostatectomy. We assessed the impact of two
      surgical techniques for dorsal vein control on surgical margins rates. PATIENTS
      AND METHODS: From August 2005 to January 2008, 480 patients underwent robot
      assisted radical prostatectomy at Roswell Park Cancer Institute. The Roswell Park
      Cancer Institute Quality Assurance robotic prostatectomy database was reviewed to
      identify all patients with prostate cancer at the apex on final pathologic
      evaluation. The rate of positive apical margins was compared between two surgical
      techniques. Group 1 consisted of 145 patients who underwent apical dissection
      after cold incision of the dorsal venous complex (DVC) without previous suture
      ligation, and group 2 consisted of 158 patients who underwent suture ligation of
      the DVC before apical dissection. RESULTS: Of 480 patients, 303 (63%) patients
      had prostate cancer in the apex. Age, body mass index, prostate-specific antigen
      level, and clinical stage were similar in both groups. The overall apical
      positive margin rate was 5%. Group 1 patients had an apical positive margin rate
      of 2%, while group 2 patients had a positive margin rate of 8% (P = 0.02). Mean
      operative blood loss estimated by the attending anesthesiologist was 331 mL and
      268 mL in group 1 and group 2, respectively (P = 0.044). One patient in group 1
      needed blood transfusion. CONCLUSIONS: Cold incision of the DVC before suture
      ligation reduces the rate of apical margin involvement during robot-assisted
      radical prostatectomy.

PMID- 19178175
TI  - Management of large (>60 g) prostate gland: PlasmaKinetic Superpulse (bipolar)
      versus conventional (monopolar) transurethral resection of the prostate.
AB  - BACKGROUND AND PURPOSE: Today, urologists around the world are encountering
      greater numbers of larger prostate glands, probably because of an initial trial
      of pharmacotherapy. The present study was performed to assess the safety and
      efficacy of bipolar transurethral resection of large prostate glands using the
      PlasmaKinetic (PK) Superpulse System. PATIENTS AND METHODS: This single-blind,
      randomized study included 70 patients with prostate gland >60 g seen on three
      dimensional transrectal ultrasonography. Patients were randomized 1:1 using
      envelopes into either a PK Superpulse transurethral resection of the prostate
      (TURP) group or conventional TURP group, and underwent the procedure accordingly.
      Perioperative and postoperative parameters included operative time, blood loss,
      need for blood transfusion, clinical transurethral resection (TUR) syndrome, and
      duration of catheterization and hospitalization. Of 70 patients, 67 were followed
      for a minimum of 9 months, and data were analyzed using SPSS software. RESULTS:
      Both groups were comparable in terms of preoperative parameters, which included
      American Urological Association Symptom Score, Qmax, gland size, and postvoid
      residual. A statistically significant difference between the two groups was found
      in terms of perioperative blood loss, change in serum sodium, and duration of
      catheterization. These complications were significantly less in the PK Superpulse
      group, with an obvious reduction in the duration of hospitalization in that
      group. CONCLUSION: The PK Superpulse System can be used as safely and effectively
      in the resection of the large gland (>60 g) as it has been reported to be in the
      resection of small and medium-sized glands. By using physiologic saline (0.9%
      NaCl) as irrigation fluid, it eliminates any danger of TUR syndrome and thus
      eliminates the conventional time limit of resection. PK Superpulse TURP is a
      promising treatment modality in the management of large prostate glands. It has
      all the features of gold-standard monopolar TURP, along with added safety and
      efficacy. It is ready to be included in the urologist's armamentarium.

PMID- 19178176
TI  - Magnetic resonance imaging as a technique for assessing noninvasive tissue
      ablation using high-intensity ultrasound: an experimental study.
AB  - BACKGROUND AND PURPOSE: As a form of noninvasive extracorporeal application,
      acoustic energy offers an alternative to nephron-sparing surgery for renal masses
      smaller than 4 cm. The availability of a reliable tool for monitoring the therapy
      is a prerequisite for safe and successful high-intensity focused ultrasound
      (HIFU) application. The aim of this study was to evaluate the morphologic
      visualization of HIFU lesions using MRI. MATERIALS AND METHODS: We used the ex
      vivo model of the isolated perfused porcine kidney. Treatment was performed using
      an experimental HIFU system. Complex lesions were induced in 10 kidneys. MRI was
      performed under constant perfusion of the kidneys. To determine the exact lesion
      size, we performed a fat-saturated, T1-weighted, volumetric interpolated breath
      hold MRI sequence. For perfusion imaging, we used a three-dimensional fast low
      angle shot sequence. Subsequently, the lesions were evaluated macroscopically.
      The width of the complex lesions was defined as x, the length as y, and the depth
      as z. RESULTS: The MRI scans showed good soft tissue contrast in all sequences.
      The mean difference for the width of the lesions was 0.2 +/- 1.1 mm; for lesion
      length and depth, it was 1.7 +/- 1.8 mm and 1.1 +/- 1.3 mm for lesion width,
      respectively. Statistical evaluation of the x values showed no significant
      difference between the macroscopic and the MRI data (P = 0.85). The y and z
      values, however, showed a statistically significant difference (P = 0.071).
      CONCLUSION: MRI could be a diagnostic tool for monitoring HIFU. Before this
      modality can be used under clinical conditions, further technical development is
      indispensable, especially with respect to reducing the measuring times.

PMID- 19178182
TI  - Structural analysis of QdtB, an aminotransferase required for the biosynthesis of
      dTDP-3-acetamido-3,6-dideoxy-alpha-D-glucose.
AB  - 3-Acetamido-3,6-dideoxy-alpha-d-glucose or Quip3NAc is an unusual deoxyamino
      sugar found in the O-antigens of some Gram-negative bacteria and in the S-layers
      of Gram-positive bacteria. It is synthesized in these organisms as a dTDP-linked
      sugar via the action of five enzymes. The focus of this investigation is on QdtB
      from Thermoanaerobacterium thermosaccharolyticum E207-71, a PLP-dependent
      aminotransferase that catalyzes the penultimate step in the production of dTDP
      Quip3NAc. For this analysis, the enzyme was crystallized in the presence of its
      product, dTDP-Quip3N, and the structure was solved and refined to 2.15 A
      resolution. QdtB is a dimer, and its overall fold places it into the well
      characterized aspartate aminotransferase superfamily. Electron density
      corresponding to the bound product reveals the presence of a Schiff base between
      C-4' of the PLP cofactor and the amino nitrogen of the sugar. Those amino acid
      side chains involved in binding the dTDP-sugar into the active site include Tyr
      183, His 309, and Tyr 310 from subunit 1 and Lys 219 from subunit 2. Notably
      there is a decided lack of interactions between the pyranosyl C-4' hydroxyl of
      the dTDP-sugar and the protein. In keeping with this observation, we show that
      QdtB can also turn over dTDP-3-acetamido-3,6-dideoxy-alpha-d-galactose. This
      investigation represents the first structural analysis of a sugar-modifying
      aminotransferase with a bound product in its active site that functions at the C
      3' rather than the C-4' position of the hexose.

PMID- 19178193
TI  - Influence of membrane surface charge and post-translational modifications to
      myelin basic protein on its ability to tether the Fyn-SH3 domain to a membrane in
      vitro.
AB  - Myelin basic protein (MBP) is a highly post-translationally modified,
      multifunctional structural component of central nervous system myelin, adhering
      to phospholipid membranes and assembling cytoskeletal proteins, and has
      previously been shown to bind SH3 domains in vitro and tether them to a membrane
      surface [Polverini, E., et al. (2008) Biochemistry 47, 267-282]. Since molecular
      modeling shows that the Fyn-SH3 domain has a negative surface charge density even
      after binding the MBP ligand, we have investigated the influence of negative
      membrane surface charge and the effects of post-translational modifications to
      MBP on the interaction of the Fyn-SH3 domain with membrane-associated MBP. Using
      a sedimentation assay with multilamellar vesicles consisting of neutral
      phosphatidylcholine (PC) and negatively charged phosphatidylinositol (PI), we
      demonstrate that increasing the negative surface charge of the membrane by
      increasing the proportion of PI reduces the amount of Fyn-SH3 domain that binds
      to membrane-associated MBP, due to electrostatic repulsion. When one of the
      phosphoinositides, PI(4)P or PI(4,5)P(2) was substituted for PI in equal
      proportion, none of the Fyn-SH3 domain bound to MBP under the conditions that
      were used. Post-translational modifications of MBP which reduced its net positive
      charge, i.e., phosphorylation or arginine deimination, increased the degree of
      repulsion of Fyn-SH3 from the membrane surface, an effect further modulated by
      the lipid charge. This study suggests that changes in membrane negative surface
      charge due to protein or lipid modifications, which could occur during cell
      signaling, can regulate the binding of the Fyn-SH3 domain to membrane-associated
      MBP and thus could regulate the activity of Fyn at the oligodendrocyte membrane
      surface.

PMID- 19178195
TI  - Methods for preparing phenolic extracts from olive cake for potential application
      as food antioxidants.
AB  - Olive cake, the most important byproduct of olive oil extraction by the two-phase
      centrifugation system, was used to obtain phenolic extracts. The extracts were
      obtained using the two constituents of this waste, vegetative water and solid
      residue, to maximize the extraction of all phenolic compounds. Different
      extraction procedures were studied, a simple and rapid extraction procedure being
      developed from the solid residue using an accelerated solvent extractor (ASE).
      Afterward, the phenolic extracts were fractionated using semipreparative HPLC to
      study the antioxidant activity of the different components. The identification of
      the phenolic compounds was carried out with an ultraperformance liquid
      chromatograph coupled to tandem mass spectrometry equipment (UPLC-ESI-MS/MS).
      With this method, a complete list of the polyphenols from the extract was
      obtained. Finally, the antioxidant activity of the phenolic extracts and the
      isolated fractions was evaluated, showing great antioxidant capacities, between
      3450 and 17900 micromol of Trolox equivalents/g of extract. With regard to the
      isolated fractions the most antioxidant were those that contained hydroxytyrosol
      and 3,4-DHPEA-EDA. The suitability of the solid residue extract obtained by the
      ASE procedure was demonstrated given the great range of phenolic compounds and
      the feasibility of production on an industrial scale.

PMID- 19178196
TI  - Introduction: aging and information technology.

PMID- 19178197
TI  - Aging and technology: the convergence of two revolutions.

PMID- 19178198
TI  - How do older netcitizens compare with their younger counterparts?
AB  - The Internet is modifying the lives of people around the world. Although many
      talk about the democratization of knowledge and information, differences remain
      among users as older netcitizens are under-represented and less involved. We use
      national and representative U.S. data, the Current Population Survey, to show age
      based differences. We complement our analysis with web-based data, the Georgia
      Tech World Wide Web User Surveys, to show Internet characteristics and trends by
      age for netcitizens. Results show that older users compose a lower share of
      Internet users than that of the total U.S. population; however, once they join
      the ranks of avid Internet users, older netcitizens are similar to their younger
      counterparts.

PMID- 19178199
TI  - Life-long learning opportunities for seniors on the web.
AB  - Web-based distance learning programs offer seniors unprecedented access to
      courses ranging from photography to business accounting. As courses and programs
      continue to multiply, new and exciting learning opportunities that are both
      flexible and high quality will be available to millions online. Web based
      learning will continue to transform education and provide access to important
      educational resources.

PMID- 19178200
TI  - Promoting independence in older persons through the internet.
AB  - New communication technologies provide hope for promoting independence in older
      persons. Today the Internet provides opportunities to socialize with others,
      participate in educational and spiritual activities, and assist with some of the
      instrumental activities of daily living. This is important in terms of quality of
      life for older persons as well as reducing expenditures for long-term care. This
      article discusses the growth in use of the Internet by the elderly and evaluates
      its ability to meet both various general needs of the population as well as needs
      specific to older persons.

PMID- 19178201
TI  - Research in gerontology: a gateway to resources on the internet.
AB  - Technology advances have made it easier to do cross-disciplinary research.
      Without the usual limitations of time, space, and subject matter, Internet users
      can navigate freely and retrieve knowledge of every conceivable area. Amid the
      vast volume of information on the net, however, finding quality material in a
      timely manner can be a daunting challenge. Even the most comprehensive Internet
      search engine today covers only 16% of the estimated 800 million pages on the
      Web. This article provides an overview of gerontology resources on the Internet,
      points out short cuts, and is intended to guide Internet users to effective
      online research.

PMID- 19178202
TI  - Computer hardware and software interfaces: why the elderly are under-represented
      as computer users.
AB  - Historically, personal computer usage by older users has been very low, and some
      have attributed it to lack of interest on the part of the elderly. This article
      argues that until recent years concepts of universal design were not implemented
      in hardware and software computer interfaces due to limitation in computing power
      and oversight by personal computer developers. The article describes how
      ownership and usage of personal computers has increased steadily since 1980s with
      older users reaching close to their population share only in recent years. A
      parallel between human origins and computer development is used to illustrate how
      developmental changes in computer design blocked or increased access to and
      ownership of personal computers. The paper concludes by implying that rapid
      changes in computer technology and design will increase computer usage by older
      users, however the computer design for the elderly should remain an important
      objective for computer developers.

PMID- 19178203
TI  - Age-related changes in a human cognitive mapping system: data from a computer
      generated environment.
AB  - Two studies investigated age-related changes in human spatial cognition. In Study
      1, younger and older adults searched computer-generated space, over several
      trials, for the location of a hidden target. Younger adults, but not older
      adults, quickly located the target and consistently returned to it. All the
      younger adults, but few of the older adults, reported using spatial relations
      among distal cues to navigate the space. In Study 2, young, middle-aged, and
      older adults performed the same task, but were provided with increased
      environmental support and pre-task training. The data pattern from Study 1 was
      replicated, with the performance of middle-aged adults falling between that of
      young and older adults. Although older adults in Study 2 reported less experience
      at completing computer-based tasks than did young and middle-aged adults, effects
      of this differential level of computer experience appeared to diminish over the
      course of experimental procedures (i.e., group differences that appeared on pre
      task non-spatial practice trials were not apparent on a similar post-task trial).
      Age-related differences in spatial cognition persisted, however. Thus, the
      current data (a) suggest that a human cognitive mapping system changes over the
      lifespan, (b) suggest that computer-generated tasks can be sensitive to those
      changes, and (c) are consistent with a substantial literature investigating age
      related changes in human and rodent spatial cognition.

PMID- 19178204
TI  - VR for the elderly: quantitative and qualitative differences in performance with
      a driving simulator.
AB  - This article presents an analysis of age differences in virtual reality (VR) use.
      One hundred forty-eight users, grouped by age and balanced by gender, answered
      questionnaires about their driving, educational, and medical histories, as well
      as their experience with computers. Participants then completed a driving
      assessment in a low-cost, PC-based virtual environment known as DriVR. Dependent
      measures included both automatic and observer recorded quantitative measures of
      driving performance, as well as participant reported qualitative measures of
      difficulty, comfort, visual clarity, delay, and simulator sickness. There were
      few age-related differences in quantitative measures, whereas qualitative
      differences between middle-aged and elderly participants were seldom found. These
      results indicated that use of VR with the elderly is quite feasible. In a
      contradiction of previously reported results, symptoms of simulator sickness
      increased with age.

PMID- 19178205
TI  - Virtual environments in the diagnosis, prevention, and intervention of age
      related diseases: a review of VR scenarios proposed in the EC VETERAN Project.
AB  - A group of worldwide virtual reality and health-care researchers have decided to
      combine their efforts in a multidisciplinary project titled VETERAN-virtual
      environments in the diagnosis, prevention and intervention of age-related
      diseases. The main goal of the VETERAN project is the tuning and testing of
      different virtual environments, designed to address the cognitive/functional
      impairments that may occur due to the aging process and age-related disorders. In
      particular the developed modules will address the problems commonly found in the
      following pathologies that have a strong impact on the elderly health care
      policy: Alzheimer's disease and other senile dementias; stroke and unilateral
      spatial neglect; mobility-related accidents within specific environments (e.g.,
      falls, shocks). The project will focus on research into clinical aspects of age
      related diseases and disorders of high morbidity and specifically target goals of
      prevention, treatment, or delay in onset. Another goal of the VETERAN project is
      to define and develop new protocols and tools to be used for general
      rehabilitation purposes. These tools will aim to provide systematic restorative
      training within the context of functionally relevant, ecologically valid
      simulated environments. This approach is hoped to optimise the degree of transfer
      of training and/or generalisation of learning to the person's real world
      environment.

PMID- 19178206
TI  - The tutoring role of mentors working with adults and elderly people with learning
      disabilities using virtual environments.
AB  - This article outlines the potential of virtual training environments in the
      rehabilitation of adults and elderly people with learning disabilities. Before
      such virtual training environments are developed, tutoring roles for mentors
      working with adults and elderly people must be investigated. This is because this
      group of people has far less expectation of and experience with computers than
      younger people with learning disabilities, for whom virtual training environments
      have already proved effective. Effective tutoring strategies employed, together
      with appropriate and well-designed virtual training environments, will be the
      outcomes of two methods suggested in this article.

PMID- 19178209
TI  - The research and controversy surrounding internet addiction.

PMID- 19178210
TI  - To get what you need: healthy and pathological internet use.
AB  - One's passion for the Internet can be healthy, pathologically addictive, or
      somewhere inbetween. Where a person falls on that continuum is determined by the
      cluster of needs that are being fulfilled by his or her Internet use and how the
      internet addresses those needs. This article suggests eight factors that can help
      clarify the healthy or unhealthy qualities of one's commitment to cyberspace
      activities, as well the effect of those activities on the person's underlying
      needs. It then explores the types of needs addressed by internet use. The
      "integration principle" is proposed as a rule of thumb for assessing pathological
      and healthy Internet use.

PMID- 19178211
TI  - Too much time online: internet addiction or healthy social interactions?
AB  - The debate surrounding the definition and validity of "Internet addiction,"a
      theorized disorder involving people who find themselves spending a lot of time
      online to the detriment of other relationships and responsibilities, remains
      unresolved. Although an understanding of human behavior is one piece of the
      equation, other pieces must be taken into consideration to appreciate the full
      picture. Societal acceptance of technology, the definitions of addictions and
      compulsions, and the effects of labeling are additional issues to take into
      consideration. When viewed from a broader perspective, online overuse looks
      surprisingly similar to normal social interactions carried out online, or simply
      one method for coping with other life, medical, or mental health problems. This
      article attempts to address these issues from this broader context while
      examining the underlying problems with research in this area to-date and offering
      suggestions for future research.

PMID- 19178212
TI  - Psychological characteristics of compulsive internet use: a preliminary analysis.
AB  - This study attempted to address the areas of Internet use and abuse by analyzing
      data derived from an online survey of 17,251 individuals. Data were collected
      from a joint project with ABC-NEWS.com, in which survey participants answered a
      36-item questionnaire regarding their Internet use and behavior. The main
      findings of the study supported previous research indicating that approximately
      6% of those surveyed met the criteria for Internet addiction. The study also
      examined the unique factors involved with sexuality on the Internet, and
      supported the frequently observed tendency for the progression of virtual sexual
      behavior to real-time sexual relations. A clear correlation was also found
      between cybersexual behavior and subsequent realtime sexual activity. In
      addition, there was an assessment of factors contributing to Internet addiction
      that was addressed using a regression analysis; the psychological regression
      found that nearly 46% of Internet addiction variance was accounted for by the
      variables examined in the study. The contribution of factors unique to Internet
      use, such as disinhibition, anonymity, ease of access, accelerated intimacy, time
      distortion (dissociation), and intensity/stimulation of online content were also
      explored. The study supports the compulsive nature of Internet use for certain
      individuals and offers suggestions for further research.

PMID- 19178213
TI  - Electronic mail dysfunction: a reality check.
AB  - Computer-mediated communication systems, including electronic mail, are systems
      that businesses employ to improve efficiency, effectiveness, and communication
      within the organization. As use of these systems proliferate, it is crucial that
      the communication systems have a positive, rather than negative impact, on the
      organization. Negative behavior could include flaming and personal use of the
      electronic mail system. Much of prior research has examined the use of electronic
      mail in academic settings. Results indicate that flaming and personal use have a
      relative high incidence. However, is electronic mail dysfunction a consistent
      reality for both academia and the business world? This case study empirically
      examines the role of electronic messaging in business firms. Specifically, this
      research investigates the usage of inter-organizational electronic messaging in
      intermediate-size firms. Electronic mail messages were analyzed in a three-site
      case study. Results indicate that dysfunctional electronic mail uses such as
      personal use and flaming have minimal incidence in a business environment.
      Implications relate to organizational professionalism and the use of students as
      electronic mail research subjects.

PMID- 19178214
TI  - Addiction to technologies: a social psychological perspective of internet
      addiction.
AB  - In recent years, there has been a large amount of scientific and media attention
      toward what some clinicians have termed "Internet addiction." This article
      asserts that habitual use or misuse of technological innovations is not a new
      phenomenon. "Internet addiction" is examined in light of research and theory on
      how people interact with technologies. The literature reveals that we have been
      concerned with the habitual use of a variety of new technologies developed during
      the twentieth century. Internet addiction is discussed in the context of issues
      such as the compulsive use of technologies such as television and video games. It
      is suggested that Internet addiction may not be a parsimonious explanation for
      the overuse of the Internet. An alternative explanation of the role that
      technologies play in the formation of maladaptive behavior is presented. In
      conclusion, it is explained that while technology may expand our capabilities
      (e.g., increases social contacts), it may also expand our capacity to express
      maladaptive behaviors and psychopathologies.

PMID- 19178215
TI  - Sensation seeking and collegiate vulnerability to internet dependence.
AB  - Past research on Internet dependence has suggested that those who are Internet
      dependent spend more time on-line, use chat rooms more frequently, play MUDs more
      often, and web surf more than nondependent Internet users, but few studies have
      examined how personality characteristics interact with Internet dependence. This
      study investigates how Internet usage, preferences, attitudes toward the
      Internet, and Internet behaviors are correlated with sensation seeking. It was
      predicted that participants who were higher in Internet usage and Internet
      behaviors would be higher in sensation seeking. Results indicated that Internet
      dependents tended to spend more time online, use E-mail, surf the web, use chat
      rooms, use MUDs, and visit cybersex sites more often than nondependent Internet
      users. However, dependents scored significantly lower on sensation seeking,
      thrill and adventure seeking, and excitement seeking than nondependent Internet
      users. It was concluded that dependents interact with the internet using a
      motivation scheme dissimilar to the physical thrill and excitement that typically
      characterize sensation seeking archetypes.

PMID- 19178216
TI  - The relationship between loneliness and internet use and abuse.
AB  - Research has found that loneliness is associated with both increased Internet use
      and Internet abuse. Causality is hard to determine. This article presents
      evidence from research on computer-mediated communication, social anxiety, and
      Internet-specific survey and field studies that support two opposing hypotheses.
      Loneliness is a byproduct of excessive Internet use because users invest in
      online relationships at the expense of real-life relationships. Lonely
      individuals are drawn to some forms of interactive activities online because of
      the possibilities of connectedness, companionship, and communities they offer.
      Limitations of these hypotheses and the potential benefits and risks of Internet
      use by the lonely also is discussed.

PMID- 19178217
TI  - Compulsive internet gambling: a new form of an old clinical pathology.
AB  - Online casinos have sprung up practically overnight into a multi-million dollar
      business, attracting a large number of gamblers worldwide. This article focuses
      on unique and psychologically significant factors that are involved in Internet
      gambling behavior, in comparison to traditional gambling procedures. Several of
      the aspects of Internet gambling, which are believed to facilitate excessive
      online gambling, are examined here in depth. These include the practical ease of
      access to online gambling and the anonymity and privacy of gambling from one's
      own home, as well as other factors. An overview of the graphical interface of
      several typical virtual casinos shows how seductive and realistic the online
      casino experience can be. The psychologically derived methods used by Internet
      casinos to make online gambling attractive, accessible, and easily operated are
      delineated. A review of the literature related to excessive traditional gambling
      behavior is used as a basis for analysis of online gambling behavior, in order to
      assess the extent of virtual gambling. The global nature of the Internet,
      combined with the limited, if not impossible, ability of local governments to
      effectively regulate or ban online gambling, will have profound psychological and
      social consequences. Studies of the effects on the psychological welfare of
      communities that underwent introduction to traditional casino gambling are
      reviewed, and evaluation is made about how virtual gambling might have negative
      social influence worldwide.

PMID- 19178218
TI  - Virtual sex addiction: when cybersex becomes the drug of choice.
AB  - This article explores how the concepts of cybersex and sexual addiction overlap.
      Sexual addiction is explained briefly to provide the reader with the necessary
      information to understand how this overlap may occur. Examination of data from
      recent studies in cybersex are presented. In addition, several cybersex case
      examples are provided to illuminate numerical findings with real-life clinical
      examples. Recommendations for future research are presented along with the
      Internet Sex Screening Test to help assess whether someone may need help with
      their cybersexual addiction.

PMID- 19178219
TI  - Treatment of computer addicts with complex co-morbid psychiatric disorders.
AB  - Computer technology is expanding at an exponential rate, and its effect on
      society and individuals is being observed in many locations and by many
      professionals. Computer-addictive behavior is characterized by excessive and
      inappropriate use of the computer that has repercussions on an individual's real
      life obligations and relationships. Currently, these unanticipated consequences
      have been variously classified as computer addiction, Internet addiction
      disorder, problematic internet use, pathological internet use, and as a new
      symptom to be added to other psychiatric conditions. Mounting evidence indicates
      that those who are vulnerable to these problems suffer from multiple co-morbid
      psychiatric disorders. The problem is further complicated because computer usage
      is so pervasive in our society that the aim of treatment cannot be abstinence. It
      must be treated as an eating disorder where the goal is to normalize computer
      activities in order to survive. Assessment of each patient consists of the
      measurement of problematic computer behavior and definition of the expectations
      they have for the effects of these activities. Because of the complexity of these
      patients' problems, treatment needs to be multidisciplinary and include cognitive
      behavior therapy, psychotropic medication, family therapy, and case managers.
      Teamwork is emphasized. Also, regular assessments at 3-month intervals are
      important both for the patient and the team. The aim of the treatment is to help
      the patient manage the inappropriate behavior and still be able to use the
      technology.

PMID- 19178220
TI  - Cyber disorders: the mental health concern for the new millennium.
AB  - Anecdotal evidence has suggested that mental health practitioners' report
      increased caseloads of clients whose primary complaint involves the Internet.
      However, little is known about the incidence, associated behaviors, attitudes of
      practitioners, and interventions involved related to this relatively new
      phenomenon. Therefore, this study surveyed therapists who have treated clients
      suffering from cyber-related problems to gather such outcome information.
      Respondents reported an average caseload of nine clients who they classified as
      Internet-addicted, with a range between 2 and 50 clients treated within the past
      year. Five general subtypes of Internet addiction were categorized based on the
      most problematic types of online applications, and they include addictions to
      Cybersex, Cyber-relationships, online stock trading or gambling, information
      surfing, and computer games. Treatment strategies included cognitive-behavioral
      approaches, sexual offender therapy, marital and family therapy, social skills
      training, and pharmacological interventions. Based on their client encounters,
      efforts to initiate support groups and recovery programs specializing in the
      treatment of Internet addiction were being considered. Finally, based upon the
      findings, this article examines the impact of cyberdisorders on future research,
      treatment, and public policy issues for the new millennium.

PMID- 19178223
TI  - Social support, self-management, and quality of life among participants in an
      internet-based diabetes support program: a multi-dimensional investigation.
AB  - The purpose of this study was to evaluate the relationship of three social
      support measurement approaches to three criteria: (a) use of an Internet-based
      disease management system, (b) diabetes self-management, and (c) quality of life.
      An online survey was conducted among participants on the "D-Net" (Diabetes
      Network) website, which provided information and support for adults with diabetes
      mellitus: A total of 221 respondents completed (a) items from the Interpersonal
      Support Evaluation Checklist, a measure of general support; (b) the Diabetes
      Support Scale, a new measure of disease-specific informational, advice, and
      empathic support; and (c) the Chronic Illness Support Survey, a measure based on
      a social ecologic framework to assess support received for chronic illness
      management from six different sources (personal, family and friends, health care
      team, worksites and organizations, neighborhood and community, and media/public
      policy). Although the three measures were moderately intercorrelated (r = .26
      .45), each was related to different aspects of D-Net use, diabetes management,
      and quality of life. These results remained significant after adjusting for
      demographic and medical condition factors (partial correlations of.15 to.33).
      This study illustrates the importance of a multidimensional approach to measuring
      social support and computer-mediated health outcomes. The advantages and
      disadvantages of applying these different conceptualizations of support in health
      promotion programs are discussed, and opportunities for future research are
      identified.

PMID- 19178224
TI  - Virtual reality and psychopathology.
AB  - Progress in the development of Virtual Reality (VR) is faster than has been
      forecast, which makes deep reflection on its potential uses and abuses absolutely
      necessary. The current article focuses on the analysis of some of the
      applications and implications of VR on psychopathology. It is obvious that they
      could be many, but we are only focusing on: (a) VR as a model to answer some
      central questions that traditionally have intrigued psychopathologists; and (b)
      VR and possible psychopathological experiences. We believe that VR has the
      potential of becoming a tool that will allow psychopathology to challenge and
      modify theoretical positions already established, and to pose new ones. This new
      way of experience can help us to find the answers to old question, and, at the
      same time, it can make new answers arise on the psychopathological and
      psychological horizon. Such answers are not only related to empirical and
      theoretical issues, but to moral ones as well. This road of research has just
      started.

PMID- 19178226
TI  - Romania: member of the large internet family.

PMID- 19178225
TI  - Therapy over the internet? Theory, research, and finances.
AB  - Behavioral telehealth is more and more often cited as an alternative mode of
      providing mental health services to individuals, families and groups. The focus
      of this paper will be to evaluate the provision of mental health services via the
      Internet, and more specifically the provision of such services through a text
      based mode of communication (such as e-mail). We will look at suggested
      theoretical modalities for online therapy, and will evaluate the research
      available on the subject as well as assess financial implications to providing
      mental health services over the Internet.

PMID- 19178227
TI  - Overview of internet development in Russia.
AB  - Internet use in Russia has been growing steadily. In the last four years the
      number of Russian Internet users grew from a few hundred thousand to over one
      million. Russian websites are diverse, and range from educational-informative to
      purely entertaining. This paper discusses several interesting and controversial
      Russian websites and possible implications associated with their use. It aims to
      understand and analyze a typical Internet user in Russia, by answering questions
      about their interests and demographics. The paper also discusses several other
      studies that were conducted in Russia on Internet use and looks at the currently
      available psychological resources on the Russian Internet.

PMID- 19178228
TI  - Introduction: beyond presence.
AB  - Presence is a concept arising from the use of sophisticated remote control
      devices and virtual reality equipment. It refers to the user's sense of being at
      a remote or virtual environment. This introduction briefly describes some of how
      the research on this concept developed, as well as some of the issues of how it
      is defined and measured. It also suggests that earlier research has been biased
      towards analyzing how attributes of technology or the environment impacts the
      individual rather than examining how individual psychological, cognitive, and
      attentional variables affect our virtual interactions. Current research is
      exploring new models and issues in the presence arena, as illustrated by this set
      of articles in this issue of CyberPsychology and Behavior. The development of
      these directions will hopefully expand our thinking about "virtual presence" to
      that of "virtual experience."

PMID- 19178229
TI  - Aspects of presence in telerelating.
AB  - Communication technologies afford new dimensions of presence for telerelating not
      available face-to-face including history, temporal and spatial ubiquity, self
      monitoring, progressive embodiment, anonymity, and involuntary feedback. These
      and other concepts are explored using examples from affordable present day
      technologies.

PMID- 19178230
TI  - Quantitative measures of presence in virtual environments: the roles of attention
      and spatial comprehension.
AB  - Given that the best measures of presence currently available are subjective self
      assessments, it is desirable to attempt to develop reliable, repeatable,
      quantitative measures. We present the results of two experiments intended to
      separate presence into measurable subcomponents: attention and spatial
      comprehension. The first experiment was a conventional dual-task study where we
      measured attentional demands of competing.virtual and real world experiences. The
      results suggest that attention may be a reasonable quantitative measure of
      presence. The study also showed that the use of sound increased the level of
      engagement experienced by participants. The second study attempted to correlate
      spatial knowledge acquisition with presence. The only component of spatial
      knowledge acquisition that was positively affected was landmark knowledge that
      improved with the addition of semantic verbal information. The data does not
      generally support a relationship between spatial comprehension and presence, but,
      again, it was found that the use of sound increased participants' sense of
      engagement in the virtual world. There are certainly other candidate
      subcomponents of presence, but we began our investigation here. An expanded
      investigation toward the development of an aggregate quantitative measure of
      presence is suggested.

PMID- 19178231
TI  - Speculations on the value of telepresence.
AB  - Synthetic environments (SE) feature computer-mediated interaction with an
      environment physically separate from the user. An SE allows human perceptual,
      cognitive, and psychomotor capabilities to be projected into distant, dangerous,
      or simulated environments. This article examines some aspects of application of
      immersive/telepresence interfaces and discusses how the new technology fits into
      a user-centered design approach to teleoperators and virtual environments. The
      central theme of an immersive/telepresence design approach is that the world may
      be displayed to a user as if that person were physically present in a
      computermediated world. However, the ability of SEs to re-create a computer
      mediated world by using immersive displays does not annul the responsibility of
      designers to tailor interfaces to meet the task-dependant needs of users. Whether
      functioning in reality or a virtual reality, interfaces must satisfy user
      information requirements to optimize performance. It does not necessarily follow
      that the combination of immersive interfaces, strict reproduction of the remote
      world, and telepresence gives users the most efficient human-machine interface.
      Other aspects of human behavior, such as concentration and attentional resource
      allocation or situation awareness, which are not necessarily encompassed by the
      concept of telepresence, need to be considered in the interface design.

PMID- 19178232
TI  - Overview of the Second International Workshop on Presence: April 6-7, 1999,
      Colchester, England.
AB  - On the 6th and 7th of April 1999, the Second International Workshop on Presence
      was held at the University of Essex. The event was organized by Jonathan Freeman
      (currently at Goldsmiths College, University of London and at the University of
      Essex during the workshop) and Wijnand IJsselsteijn (IPO, Center for Research on
      User-System Interaction) as part of the European Commission ACTS TAPESTRIES
      project. The TAPESTRIES project was managed by the UK Independent Television
      Commission (ITC) and the workshop was sponsored by SONY, BT, and the ITC. The
      workshop program is followed by a brief introduction to presence and then by
      short summaries of each of the papers.

PMID- 19178235
TI  - MYTHSEEKER Project Status Summary.
AB  - This is a summary of the present status of The MYTHSEEKER Project. The first
      section provides a brief synopsis of the project's purpose and approach. The
      second section summarizes present activity in a number of directions-including
      decisions that are shaping development. The third section outlines the next steps
      for development programming, the initial software product, and a communications
      network of MYTHSEEKER Centers. Some extended viewpoints are mentioned.

PMID- 19178236
TI  - Internet gambling and pornography: illustrative examples of the psychological
      consequences of communication anarchy.
AB  - Two areas of Internet behavior, gambling and pornography distribution, are
      examined for what they reveal about the profound social and psychological changes
      caused by recent advances in communication technology. The overview of these
      domains clearly shows that there will be an expected increase in people
      presenting for treatment with Internet behavior related difficulties, and that
      their treatment will be, at present, uninformed by any specific empirical
      research. These two domains are used as examples to illustrate how the Internet
      is creating a paradigm shift in the basic nature of an individual's relationships
      to local, state, and federal governments. It is no longer possible for people,
      even minors, to be fully protected by their governments from material deemed
      harmful by the community one lives in. This is demonstrated by a review of the
      current availability, in millions of homes nationwide, of the opportunity to
      experience Internet casino gambling and to acquire pornographic material not sold
      in United States adult bookstores. The psychological effect of the increased need
      for individual responsibility in the access to potentially harmful domains is not
      well understood at this time. This article is a call for the kind of basic
      research that will delineate the base rates for pathological involvement in
      online gambling and pornography, as a means of discovering the potential negative
      psychological consequences of the inability to regulate Internet content.

PMID- 19178237
TI  - The world wide web: exploring a new advertising environment.
AB  - The World Wide Web currently boasts millions of users in the United States alone
      and is likely to continue to expand both as a marketplace and as an advertising
      environment. Three experiments explored advertising in the Web environment, in
      particular memory for ads as they appear in everyday use across the Web.
      Experiments 1 and 2 examined the effect of advertising repetition on the
      retention of familiar and less familiar brand names, respectively. Experiment 1
      demonstrated that repetition of a banner ad within multiple web pages can improve
      recall of familiar brand names, and Experiment 2 demonstrated that repetition can
      improve recognition of less familiar brand names. Experiment 3 directly compared
      the retention of familiar and less familiar brand names that were promoted by
      static and dynamic ads and demonstrated that the use of dynamic advertising can
      increase brand name recall, though only for familiar brand names. This study also
      demonstrated that, in the Web environment, much as in other advertising
      environments, familiar brand names possess a mnemonic advantage not possessed by
      less familiar brand names. Finally, data regarding Web usage gathered from all
      experiments confirm reports that Web usage among males tends to exceed that among
      females.

PMID- 19178238
TI  - Interactive E-mail journals: a model for providing psychotherapeutic
      interventions using the internet.
AB  - The communication medium of the Internet affords psychologists an unprecedented
      opportunity to provide psychological services to populations who might not
      ordinarily present to the mental health system but who may nevertheless benefit
      from psychological intervention. Because the Internet is primarily a medium of
      the written word, one of the difficulties in providing online psychological
      services is developing models appropriate to text-only delivery. This article
      discusses a model for providing online psychological interventions based on the
      similarity of E-mail composition to traditional journal writing. Two different
      approaches to interactive online journaling, the Intensive Journal method
      developed by Progoff and dream journaling, are examined regarding their possible
      application to delivery within the text-based medium of the Internet.

PMID- 19178239
TI  - Development of a computerized psychiatric diagnostic interview for use by mental
      health and primary care clinicians.
AB  - A diagnostic screening tool was developed to simulate a clinical psychiatrist
      intake interview including DSM-IV Axis I and II differential diagnosis plus
      evaluation of dangerousness, and optionally psychiatric medication history,
      family history, developmental history, and treatment goals (PsychDiagnoser
      software). The performance of the software as a diagnostic screening tool was
      evaluated in a private practice outpatient setting with 62 new patients. The
      software was well accepted with 60 patients receiving a computer diagnosis. The
      computer diagnosis for Axis I, Axis II, and dangerousness was compared with the
      definitive clinical diagnosis from a psychiatrist. Sensitivity and specificity
      calculations showed PsychDiagnoser software to be an affective screening tool for
      the Axis I and II disorders prevalent to this population (major depression,
      bipolar I and II, alcohol and drug abuse, no personality disorder, borderline
      personality disorder) and for dangerousness.

PMID- 19178240
TI  - Augmented reality in Parkinson's disease.
AB  - This article presents an augmented reality-based therapeutic device designed to
      overcome gait problems associated with Parkinson's Disease. A normal model of
      gait is proposed followed by a model of Parkinsonian gait with the goal of
      construction of a gait-enabling therapeutic device. The fundamental underlying
      tenet of the model is that vision pathology is responsible for the majority of
      Parkinsonian gait pathology. The basis for such a claim is the well documented
      phenomenon known as Kinesia Paradoxa, whereby, in the presence of certain so
      called visual cues, a PD subject can be transformed from a totally immobile,
      helpless victim of this disease into a near normal-walking individual. Several
      gait-enabling devices are also described.

PMID- 19178241
TI  - From imagination to virtual reality: the future of clinical psychology.
AB  - The possible role of virtual reality (VR) in clinical psychology derives
      prevalently from the central role occupied by the imagination and by memory in
      psychotherapy. These two elements, which are fundamental in the life of everyone,
      present absolute and relative limits to individual potential. Thanks to virtual
      experiences, it is possible to transcend these limits. The re-created world may
      be more vivid and real at times than the one that most subjects are able to
      describe through their own imagination and through their own memory. This article
      focuses on imaginative techniques to find new ways of applications in therapy. In
      particular, the way VR can be used to improve the efficacy of current techniques
      is explored. VR produces a change with respect to the traditional relationship
      between client and therapist. The new configuration of this relationship is based
      on the awareness of being more skilled in the difficult operations of recovery of
      past experiences through the memory and of foreseeing future experiences through
      the imagination. At the same time, subjects undergoing treatment perceive the
      advantage of being able to recreate and use a real experiential world within the
      confines of their therapists's clinical offices.

PMID- 19178242
TI  - The "Cyberlink" brain-body interface as an assistive technology for persons with
      traumatic brain injury: longitudinal results from a group of case studies.
AB  - A longitudinal study of traumatic brain-injured and comatose participants
      suggests that these individuals are able to learn to use a mental interface
      device to navigate a maze and perform some basic communication. The device, known
      as the "Cyberlink," uses electrooculargraphic, electromyographic, and
      electroencephlagraphic signals collected at the forehead to control cursor
      movement. Further details of the operation of the device and the set-up
      procedures are reported. Six adults, all of whom had traumatic brain injury or
      were believed to be comatose, participated in the study over a 7-month period.
      Initially, only one participant, who had previously used the device, could
      navigate the maze. At the end of the study all participants could navigate the
      maze, albeit with a high variability in success rate. Reasons for the variability
      obtained are postulated. The majority of participants could also use the device
      to type simple words. Positive behaviors and increases in attention span were
      also observed. The diagnosis of one participant was upgraded from coma to
      traumatic brain stem injury as a result of data collected during the study.
      Controls were built into the study in order to demonstrate intention. Further
      developments of the device and other applications where it may be useful are
      discussed.

PMID- 19178243
TI  - Archetypal conceptualization of cyberspace as the Celtic otherworld.
AB  - The Internet presents us with a wide range of novel experiences for which we do
      not have corresponding "real-world" experiences that would help us in
      psychologically organizing our understanding of this new communication medium.
      Our difficulty in organizing our psychological experiences with the Internet and
      cyberspace results in our inappropriately applying models developed from "real
      world" experiences to the new medium of cyberspace. This article proposes that,
      on a fundamental level, our experiences with cyberspace are being unconsciously
      organized around the archetypal theme expressed in the Celtic conceptualization
      of the Otherworld, or sidhe. The parallels between cyberspace and the Celtic
      Otherworld are explored and the implications for understanding our reactions to
      the Internet are discussed.

PMID- 19178245
TI  - Virtual environments for targeting cognitive processes: an overview of projects
      at the University of Southern California.
AB  - The Virtual Environments Laboratory at the University of Southern California
      (USC) has initiated a research program aimed at developing virtual reality (VR)
      technology applications for the study, assessment, and rehabilitation of
      cognitive processes. This technology is seen to offer many advantages for these
      aims. The status of two ongoing VR projects will be discussed in this article.
      The projects outlined are being conducted via cooperative efforts with both the
      Integrated Media Systems Center and the Information Sciences Institute at USC.
      These departments consist of a multidisciplinary group of scientists that
      represents engineering, computer science, communications, information technology,
      education, and psychology. This mix of expertise has served to facilitate the
      development of these projects via an integrated approach to VR application
      development. The first project involves the development of a series of
      ImmersaDesk-delivered visuospatial tests and training tools that leverage the
      interactive, dynamic, and 3D assets that are available with current VR
      technology. The second project involves a head mounted display (HMD) VR system
      for the study, assessment, and possible rehabilitation of attention disorders. It
      is believed that these projects target cognitive variables that are well matched
      to the current strengths and limitations that exist with presently available VR
      technology.

PMID- 19178246
TI  - Virtual environment interaction through 3D audio by blind children.
AB  - Interactive software is actively used for learning, cognition, and entertainment
      purposes. Educational entertainment software is not very popular among blind
      children because most computer games and electronic toys have interfaces that are
      only accessible through visual cues. This work applies the concept of interactive
      hyperstories to blind children. Hyperstories are implemented in a 3D acoustic
      virtual world. In past studies we have conceptualized a model to design
      hyperstories. This study illustrates the feasibility of the model. It also
      provides an introduction to researchers to the field of entertainment software
      for blind children. As a result, we have designed and field tested AudioDoom, a
      virtual environment interacted through 3D Audio by blind children. AudioDoom is
      also a software that enables testing nontrivial interfaces and cognitive tasks
      with blind children. We explored the construction of cognitive spatial structures
      in the minds of blind children through audio-based entertainment and spatial
      sound navigable experiences. Children playing AudioDoom were exposed to first
      person experiences by exploring highly interactive virtual worlds through the use
      of 3D aural representations of the space. This experience was structured in
      several cognitive tasks where they had to build concrete models of their spatial
      representations constructed through the interaction with AudioDoom by using
      Legotrade mark blocks. We analyze our preliminary results after testing AudioDoom
      with Chilean children from a school for blind children. We discuss issues such as
      interactivity in software without visual cues, the representation of spatial
      sound navigable experiences, and entertainment software such as computer games
      for blind children. We also evaluate the feasibility to construct virtual
      environments through the design of dynamic learning materials with audio cues.

PMID- 19178247
TI  - Gender issues in the use of virtual environments.
AB  - Gender differences in cognitive and behavioral performance have been reported
      throughout the psychological literature. Consequently, gender differences should
      be considered and controlled for when cognitive research is conducted in virtual
      environments (VEs). These variables may include gender-related differences in
      cognitive performance, susceptibility for cybersickness, and the impact of sex
      hormones on cognition. Such issues are addressed in the context of a recent VE
      study of the visuospatial ability referred to as mental rotation. The Mental
      Rotation Test (MRT), a paper and pencil measure, has been shown to produce one of
      the largest gender differences in the cognitive literature. The outcomes of the
      MRT are in favor of males. However, results reported from a Virtual Reality
      Spatial Rotation (VRSR) test demonstrate no gender differences when subjects were
      able to manually manipulate the stimuli in a VE. Further analysis uncovers gender
      differences in the patterns of associations between verbal and spatial tasks and
      performance on VRSR. Results are discussed in terms of dimensionality factors and
      hemispheric lateralization.

PMID- 19178248
TI  - Effects of virtual reality on symptom distress in children receiving
      chemotherapy.
AB  - This study tested the premise that virtual reality (VR) as a distraction
      intervention could mitigate chemotherapy-related symptom distress in children
      with cancer aged 10-17 years. Cancer treatments are intensive and difficult to
      endure. Distraction interventions are effective because the individual
      concentrates on pleasant or interesting stimuli instead of focusing on unpleasant
      symptoms. VR as a distraction intervention is both immersive and interactive. For
      this study the individual wore a Virtual IO(R) headset during a single
      intravenous chemotherapy treatment. Participants chose one of three commercially
      available, CD ROM-based scenarios: Magic Carpet, Sherlock Holmes Mystery, and
      Seventh Guest(R). An interrupted time series design with removed treatment was
      used to answer these research questions: (1) Is VR an effective distraction
      intervention for reducing chemotherapy-related symptom distress in children? and
      (2) Does VR have a lasting effect? The convenience sample consisted of 11
      children receiving outpatient chemotherapy. The Symptom Distress Scale (SDS) and
      the State-Trait Anxiety Inventory for Children (STAIC-1) were used to measure the
      dependent variable of symptom distress. Repeated-measures ANOVA were used for
      data analysis. Data analysis of the SDS suggested that the VR intervention was
      effective at reducing the level of symptom distress immediately following the
      chemotherapy treatment (p <.10), but did not have a lasting effect. Analysis of
      the STAIC-1 demonstrated high levels of anxiety during the initial chemotherapy
      treatment that decreased during subsequent treatments. State anxiety levels were
      not influenced by the VR intervention. This study supports the application of VR
      as a distraction intervention.

PMID- 19178249
TI  - The treatment of claustrophobia with virtual reality: changes in other phobic
      behaviors not specifically treated.
AB  - This study was designed to determine the effectiveness of Virtual Reality (VR)
      exposure in the case of a patient with a diagnosis of two specific phobias
      (claustrophobia and storms) and panic disorder with agoraphobia. The treatment
      consisted of eight, individual, VR-graded exposure sessions designed specifically
      to treat claustrophobia. We obtained data at pretreatment, posttreatment, and 3
      month follow-up on several clinical measures. Results point out the effectiveness
      of the VR procedure for the treatment of claustrophobia. An important change
      appeared in all measures after treatment completion. We also observed a
      generalization of improvement from claustrophobic situations to the other
      specific phobic and agoraphobic situations that were not treated. We can conclude
      that VR exposure was effective in reducing fear in closed spaces, in increasing
      self-efficacy in claustrophobic situations, and in improving other problems not
      specifically treated. Moreover, changes were maintained at 3 months after
      treatment.

PMID- 19178250
TI  - Psychological variables and reality judgment in virtual environments: the roles
      of absorption and dissociation.
AB  - Literature on virtual reality (VR) and psychology has focused on the influence
      that some basic psychological processes have on VR. Although psychological
      processes may be defined as common to all humans, there are individual
      differences that might make it difficult to provide the same VR experience for
      everyone. Of the several personality and psychological variables that might be
      relevant to the VR field, this study focuses on two: absorption and dissociation.
      Both psychological dimensions are deeply interrelated and might play an important
      role in the immersion of subjects in virtual environments and in the reality
      attributions they make. Thus, the purpose of this study was to ascertain
      personality correlates on differences regarding the VR experience. The subjects
      were 39 psychology undergraduate students who were immersed in a VR environment
      for 15 minutes. Our data suggest that both absorption and dissociation influenced
      central issues regarding reality judgment in VR.

PMID- 19178251
TI  - Body image and virtual reality in eating disorders: is exposure to virtual
      reality more effective than the classical body image treatment?
AB  - Body image (BI) disturbances are considered to be central in eating disorders
      (ED) psychopathology. There are few studies focused on the treatment of BI
      disturbances in ED, and most of them have used "traditional methods." The purpose
      of the present study was to probe the effectiveness of one specific component in
      the assessment and treatment of BI in ED by means of virtual reality (VR). Two
      treatment conditions were applied: (a) The Standard Body Image Treatment
      Condition (SBIT) and (b) the VR Condition. Thirteen eating disordered patients
      were randomly assigned to one of those conditions. No differences between both
      conditions were found in general ED measures, but patients treated in the VR
      condition showed a greater significant improvement in specific BI measures. These
      results suggest that BI treatment with VR could be more targeted to its
      disturbances. than traditional techniques are.

PMID- 19178252
TI  - PET supports the hypothesized existence of a male sexual brain algorithm that may
      respond to treatment combining psychotherapy with virtual reality.
AB  - Could a brain circuit exist, verifiable using positron emission tomography (PET),
      that links coitus and its dysfunctions, such as impotence? Could re-establishing
      normal sexual functioning be linked with the normalization of some sort of
      altered brain metabolism utilizing a therapeutic project that uses psychodynamic
      psychotherapy integrating virtual reality (VR)? A Brain PET Scan and a self
      administered sexual activity questionnaire were given to 11 heterosexual patients
      affected by impotence due to psychological causes, both before and approximately
      6 months after a cycle of psychodynamic psychotherapy. Seven randomly-selected
      patients received psychotherapy with VR technology using the Optale Method. PET
      data, used to indicate glucose consumption in various brain areas, were compared
      with data from normal patients, and a statistical analysis was run. Alterations
      in cerebral metabolic functioning were displayed in the following areas: frontal
      cortex, nucleus caudatus, and thalamus. The seven patients who received
      psychotherapy with VR technology "normalized" in these same areas and attained
      satisfactory sexual performance. The existence of a male sex algorithm may be
      hypothesized that links the frontal cortex, nucleus caudatus, and thalamus, and
      explains its action on cortical motor areas and/or on the medial preoptic area of
      the hypothalamus, which may respond to treatment combining psychotherapy with VR.

PMID- 19178256
TI  - Progress in virtual therapy.

PMID- 19178253
TI  - Clinical observations during virtual reality therapy for specific phobias.
AB  - Virtual environments offer a new method of providing exposure therapy to patients
      with specific phobias. Although the stimuli (three-dimensional computer
      simulations) is new, the method of systematically desensitizing the patient to
      phobic stimuli until habituation occurs is a concept that was formally introduced
      by Joseph Wolpe over 40 years ago. Our article discusses some of the clinical
      observations that have been made during nearly 500 virtual reality exposure
      therapy sessions with patients and research participants who have come to our
      center in the past 15 months with a fear of flying or driving.

PMID- 19178257
TI  - Overview of the virtual reality and mental health symposium.

PMID- 19178258
TI  - A virtual environment for the treatment of chronic combat-related post-traumatic
      stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is one of the most disabling
      psychopathological conditions affecting the veteran population. An estimated
      830,000 U.S. veterans currently have symptoms of chronic combat-related PTSD. No
      therapeutic approach has proven to be consistently effective in the management of
      combat-related PTSD. Behavior therapies with an exposure element have proven more
      effective than most other types of treatment, but a significant number of
      patients do not seem to benefit from them, possibly because of difficulties
      imagining, visualizing, or describing their traumatic experiences. In this
      article, we describe Virtual Vietnam, a set of two virtual environments we have
      developed for the treatment of combat-related PTSD, and its use as one component
      of a comprehensive treatment program.

PMID- 19178259
TI  - Mental health implications for presence.
AB  - "Presence," as discussed in the virtual reality (VR) literature, is the sense of
      truly being in a virtual place. This literature explores many aspects of presence
      including interactive and environmental factors. This exploration has generally
      ignored the impact of the individual's mental status on the experience of
      presence. Mental disorders such as depression, anxiety, and psychosis may each
      define a population with specific tendencies to respond to VR in particular ways.
      To fully understand the experience of presence in virtual environments, we must
      understand more about the impact of different mental states on presence. Such an
      understanding will improve our insight into the construct of presence, assist in
      improved design of virtual environments, and better inform us about how virtual
      environments can be applied in the treatment of emotional disorders.

PMID- 19178260
TI  - Virtual reality promotes visual and cognitive function in rehabilitation.
AB  - The purpose of this study is to evaluate the effectiveness of virtual reality
      (VR) in cognitive and perceptual dysfunction. Patients who have suffered cerebro
      vascular accidents may exhibit visual field and auditory processing deficits,
      which may pose a challenge for clinicians in the rehabilitation setting. Visual
      neglect and auditory processing can greatly interfere with a person's ability to
      perform activities of daily living. These can include reading, writing, dressing,
      self care activities, communicating, and establishing eye contact during
      conversational exchanges. Occupational therapists and speech-language
      pathologists coordinate their treatment goals to address these cognitive and
      visual perceptual deficits for improved communication skills and performance of
      daily functional activities. Our focus is to demonstrate how VR can be used in
      conjunction with traditional therapeutic techniques to facilitate a patient's
      ability to follow multi-unit commands and increase visual attention to the
      affected side. The VR technology used in this particular procedure is
      nonimmersive, which allows for full body movement and immediate feedback. Future
      efforts to determine the feasibility of VR in other aspects of rehabilitation are
      currently being explored.

PMID- 19178261
TI  - Quantitative video analysis of complex epileptic seizures during videotelemetry:
      increasing the reliability of EEG correlation and behavioral autocorrelation.
AB  - The analysis of complex partial seizures constitutes a major clinical problem.
      Because of the partial perturbation of consciousness during such episodes,
      variable behavioral patterns may emerge. After seizures are captured by
      simultaneous video-electroencephalographic (EEG) monitoring, the offline analysis
      involves autocorrelation of patient behavior over successive seizures and
      correlation with EEG findings. To avoid attempting to quantify the relationships
      between behavioral observations and the EEG findings "by eye," a process
      performed by a neurologist that can be quite subjective, quantitative rendering
      of relevant movements captured by video monitoring is helpful. The resulting
      graphic data of relevant movement phenomena can be compared with EEG data and
      with patient behavior in multiple possible or actual seizure episodes. This
      quantitative movement data can be generated and linked to the monitoring system
      using a video preprocessing device. Preliminary results indicate that the
      preprocessor output data may be autocorrelated over multiple seizures and may
      also be correlated with simultaneous EEG features to achieve greater reliability
      in categorization of seizure type and focus of origin in some cases.

PMID- 19178262
TI  - Preventing teen smoking with virtual reality.
AB  - Smoking incidence is rising among adolescents but not adults. Although many
      prevention programs are effective, there is room for improvement. This pilot
      project combined the welldocumented benefits of Life Skills Training (LST) with
      the unique multisensory, 3D qualities of virtual environment (VE) technology to
      address some of the disadvantages of traditional prevention programs. In an 8
      week pilot study, 72 seventh-grade students were randomly assigned to either LST,
      VE, or nonintervention control groups. The VE system included goggles,
      synthesized speech, spatial trackers on head and hand, a hand-held controller,
      and a speech recognition system. Questionnaires measured participants' smoking
      knowledge, attitudes, and behavior. A bogus pipeline procedure was used to
      increase reliability of the self-report measures. Pre-exposure data showed no
      significant differences between groups on the questionnaire. Post-exposure data
      indicated improvements in attitudes in the LST and VE groups. In addition, the VE
      group showed more accurate information concerning peer and adult cigarette use
      and more likelihood of using coping and refusal skills. Usability and
      acceptability questionnaire data showed ease of use and learning and that
      participants would use VE technology frequently if it were available to them at
      school. These data indicated that this VE application is a promising tool for
      keeping teens healthy.

PMID- 19178263
TI  - Differences on presence and reality judgment using a high impact workstation and
      a PC workstation.
AB  - The purpose of this study was to analyze differences in reality judgements made
      by subjects and their sense of presence when using the virtual reality (VR)
      settings of different VR workstations. The two workstations were (1) a high
      impact computer graphics workstation (Silicon Graphics) with a high quality head
      mounted display (FS5, Virtual Research) and a 3D joystick (Division) and (2) PC
      Pentium II-based platform with an AccelEclipse Graphical Card (AccelGraphics)
      with a medium quality head mounted display (V6, Virtual Research) and a 2D mouse.
      For measuring the sense of presence and reality, we used a 15-item questionnaire
      designed for this purpose that assesses the level of immersion and reality of the
      VR settings, availability of interaction with the VR environment, and emotions
      and bodily sensations experienced while immersed in the VR world. The subjects
      were 69 undergraduate students that volunteered for this study and were assigned
      at random to the two experimental workstations. Results indicated that there are
      no statistical differences in presence or reality judgment between both
      experimental conditions. This is an interesting finding because of the importance
      of reducing the cost of the equipment in the VR field.

PMID- 19178264
TI  - Norms and validity of the DriVR: a virtual reality driving assessment for persons
      with head injuries.
AB  - This article presents the results of two studies of a new driving simulator
      called "DriVR." The first, normative study examined the performance of an
      uninjured driving population on the simulator. The driving ability of 148
      participants in eight age categories was assessed using DriVR. The second,
      discriminative validity study examined DriVR's ability to discriminate between
      the performance of head-injured and uninjured adults. We administered the DriVR
      assessment to 17 head-injured adults. The performance of this group was compared
      to that of a subgroup of uninjured participants that matched the brain-injured
      participants in age, gender, and years of education. In general, DriVR's measures
      showed age-related changes in participant performance and were able to
      discriminate between head-injured and uninjured participants. These results
      suggested that age norms would be useful for analyzing the performance of head
      injured clients who are being assessed with DriVR. It should be noted, however,
      that these studies did not examine DriVR's ability to predict performance in
      real, on-the-road tests.

PMID- 19178265
TI  - VREPAR projects: the use of virtual environments in psycho-neuro-physiological
      assessment and rehabilitation.
AB  - Due, in large part, to the significant advances in PC hardware that have been
      made over the last 3 years, PC-based virtual environments are approaching
      reality. Virtual Reality Environments for Psychoneurophysiological Assessment and
      Rehabilitation (VREPAR) are two European Community funded projects (Telematics
      for health-HC 1053/HC 1055, http:// www.psicologia.net) that are trying to
      develop a PC-based virtual reality system (PC-VRS) for the medical market that
      can be marketed at a price that is accessible to its possible endusers
      (hospitals, universities, and research centres) and that would have the modular,
      connectability, and interoperability characteristics that the existing systems
      lack. In particular, the projects are developing three hardware/software modules
      for the application of the PCVRS in psycho-neuro-physiological assessment and
      rehabilitation. The chosen development areas are eating disorders (bulimia,
      anorexia, and obesity), movement disorders (Parkinson's disease and torsion
      dystonia) and stroke disorders (unilateral neglect and hemiparesis). This article
      describes the rationale of the modules and the preliminary results obtained.

PMID- 19178266
TI  - VREPAR 2: VR in eating disorders.
AB  - Virtual Reality Environments for Psychoneurophysiological Assessment and
      Rehabilitation (VREPAR) are two European Community funded projects (Telematics
      for health-HC 1053/HC 1055-http://www.psicologia.net) whose aim is (a) to develop
      a PC based virtual reality system (PC-VRS) for the medical market that can be
      marketed at a price that is accessible to its possible endusers (hospitals,
      universities, and research centres) and that would have the modular,
      connectability and interoperability characteristics that the existing systems
      lack; and (b) to develop three hardware/software modules for the application of
      the PC-VRS in psychoneurophysiological assessment and rehabilitation. The chosen
      development areas are eating disorders (bulimia, anorexia, and obesity), movement
      disorders (Parkinson's disease and torsion dystonia), and stroke disorders
      (unilateral neglect and hemiparesis). In particular, the VREPAR 2 project is now
      testing the eating disorders module on a clinical sample.

PMID- 19178267
TI  - Evaluation of the psycho-oncological effectiveness of the bedside wellness
      system.
AB  - This article describes how a virtual forest walk system (a bedside Wellness
      system) is expected to help cancer patients to relax and become more positive
      emotionally. It is also expected that the beautiful scenery (with wind, scents,
      and sounds) will refresh patients and that the evoked changes in the natural
      world will relax them. We have demonstrated the possible uses of virtual reality
      (VR) technology in the care of patients' mental health; however, we still have to
      improve the VR technology itself and investigate how to utilize it most
      effectively. It is essential that VR technology may be able to construct virtual,
      but realistic, environments that patients can enjoy without being caused
      additional stress or fatigue. This type of medical VR system may be effective in
      improving the quality of life of not only cancer patients, but also of the
      elderly.

PMID- 19178273
TI  - Composition of essential oil compounds from different Syrian populations of
      Origanum syriacum L. (Lamiaceae).
AB  - The chemical compositions of the essential oil compounds of 117 individual plants
      belonging to 11 Syrian populations of Origanum syriacum L. (Lamiaceae) were
      studied by GC-FID and GC-MS. The composition was dominated by carvacrol and/or
      thymol with a high degree of polymorphism in the occurrence of these two
      compounds between the different populations. In three populations carvacrol was
      dominating, with thymol being present only in minor amounts, whereas in only one
      population thymol was the main compound, with carvacrol only in traces. In all
      other populations both carvacrol and thymol were present as major compounds. No
      geographical pattern could be detected for the occurrence of the chemotypes.
      Thymoquinone, a promising anticancer candidate, was present in the extracts in a
      wide range between 0.04 and 23.7%.

PMID- 19178274
TI  - Effects of lactate on beef heart mitochondrial oxygen consumption and muscle
      darkening.
AB  - The mechanism of lactate-induced beef color darkening is unclear. Our objective
      was to evaluate the ability of mitochondria isolated from bovine cardiac muscle
      to utilize lactate as a fuel for respiration. Addition of lactate (4, 8, and 16
      mM) to isolated bovine cardiac mitochondria resulted in state IV oxygen
      consumption at pH 7.2 and 25 degrees C measured using a Clark oxygen electrode.
      Combining mitochondria with lactate, LDH, and NAD increased state IV oxygen
      consumption compared with that of lactate alone (p < 0.05). Moreover, oxygen
      consumption resulting from the addition of lactate-LDH-NAD (0.2 mM each) was
      comparable to oxygen consumption resulting from the direct addition of NADH (0.2
      mM) to mitochondria at pH 7.2. Rotenone reduced (p < 0.05) lactate-mediated
      darkening in bovine cardiac muscle homogenates. Lactate-induced beef color
      darkening may be due to increased oxygen consumption by mitochondria, which out
      competes myoglobin for oxygen and results in dark colored muscle.

PMID- 19178275
TI  - In situ preparation and modification of supported lipid layers by lipid transfer
      from vesicles studied by QCM-D and TOF-SIMS.
AB  - The study of lipid transfer between lipid membranes is of great interest for the
      fundamental understanding of this complex and important process and, furthermore,
      for providing a new avenue for the in situ modification of supported lipid
      bilayers (SLBs). SLBs are conveniently formed by vesicle spreading onto a solid
      support, but this method is limited to conditions (i.e., combination of vesicle
      lipid composition, surface chemical properties, and buffer) such that the
      vesicles break spontaneously upon adsorption to the surface. Many SLB
      compositions are not accessible by this approach. In the present study, we give
      an example of how lipid transfer can be made use of to form lipid layers with
      striking new features, notably with respect to stability. After lipid transfer
      between negatively charged POPS small unilamellar vesicles and a positively
      charged POEPC SLB on TiO2, an SLB is obtained, which, upon exposure to SDS,
      leaves behind a lipid monolayer. It is shown how this monolayer can be used for
      creating new SLBs. The several step procedure, bilayer formation, lipid transfer,
      removal of a lipid monolayer and the reassembly of a bilayer, is monitored in
      real time by the quartz crystal microbalance with a dissipation (QCM-D)
      technique, and the lipid composition is analyzed for each step in postpreparation
      spectroscopic analyses using time-of-flight secondary ion mass spectrometry (TOF
      SIMS). Comparison of the measured signal ratios with those of the reference
      samples containing known fractions of D31-POPS directly shows that the relative
      concentration of D31-POPS is approximately 50% in the SLB after D31-POPS
      exchange, significantly higher in the monolayer prepared in situ by SDS rinse,
      and approximately 20-25% after reassembly of the SLB using POEPC vesicles. The
      results thus provide unambiguous evidence for extensive lipid transfer between
      the initial POEPC SLB and D31-POPS vesicles in solution. We suggest that the
      reassembled SLB has a significant asymmetry between the two leaflets, and we
      propose that the described method is promising for the in situ preparation of
      asymmetric SLBs.

PMID- 19178277
TI  - Properties of extruded vital wheat gluten sheets with sodium hydroxide and
      salicylic acid.
AB  - This paper presents a novel approach to improve the barrier and mechanical
      properties of extruded glycerol-plasticized vital wheat gluten sheets. The sheets
      were extruded with a single screw extruder at alkaline conditions using 3-5 wt %
      NaOH. Salicylic acid (SA), known to improve the extrudability of wheat gluten,
      was also added alone or in combination with NaOH. Oxygen transmission rate and
      volatile mass measurements, tensile tests, protein solubility, glycerol
      migration, infrared spectroscopy, and electrophoresis were used to assess the
      properties of the extrudate. Electrophoresis showed that the gluten/glycerol
      sheet and the sheet with 3 wt % NaOH and 1 wt % SA contained the same building
      blocks in terms of proteins and protein subunits, although the protein solubility
      in these samples was different. The oxygen barrier, at dry conditions, was
      improved significantly with the addition of NaOH. On the other hand, the addition
      of salicylic acid yielded poorer barrier properties. The extrudate was placed on
      a blotting paper and its aging properties were investigated during the first 120
      days. It was observed that the extrudate with 3 wt % NaOH had the most suitable
      combination of properties (low oxygen permeability, large strain at break, and
      relatively small aging-induced changes in mechanical properties); the reason is
      probably due to low plasticizer migration and an optimal protein
      aggregation/polymerization.

PMID- 19178276
TI  - Spore photoproduct lyase catalyzes specific repair of the 5R but not the 5S spore
      photoproduct.
AB  - Bacterial spores are remarkable in their resistance to chemical and physical
      stresses, including exposure to UV radiation. The unusual UV resistance of
      bacterial spores is a result of the unique photochemistry of spore DNA, which
      results in accumulation of 5-thyminyl-5,6-dihydrothymine (spore photoproduct, or
      SP), coupled with the efficient repair of accumulated damage by the enzyme spore
      photoproduct lyase (SPL). SPL is a member of the radical AdoMet superfamily of
      enzymes, and utilizes an iron-sulfur cluster and S-adenosylmethionine to repair
      SP by a direct reversal mechanism initiated by H atom abstraction from C-6 of the
      thymine dimer. While two distinct diastereomers of SP (5R or 5S) could in
      principle be formed upon UV irradiation of bacterial spores, only the 5R
      configuration is possible for SP formed from adjacent thymines in double helical
      DNA, due to the constraints imposed by the DNA structure; the 5S configuration is
      possible in less well-defined DNA structures or as an interstrand cross-link. We
      report here results from HPLC and MS analysis of in vitro enzymatic assays on
      stereochemically defined SP substrates demonstrating that SPL specifically
      repairs only the 5R isomer of SP. The observation that 5R-SP, but not 5S-SP, is a
      substrate for SPL is consistent with the expectation that 5R is the SP isomer
      produced in vivo upon UV irradiation of bacterial spore DNA.

PMID- 19178278
TI  - Highly specific and sensitive electrochemical genotyping via gap ligation
      reaction and surface hybridization detection.
AB  - This paper developed a novel electrochemical genotyping strategy based on gap
      ligation reaction with surface hybridization detection. This strategy utilized
      homogeneous enzymatic reactions to generate molecular beacon-structured allele
      specific products that could be cooperatively annealed to capture probes stably
      immobilized on the surface via disulfide anchors, thus allowing ultrasensitive
      surface hybridization detection of the allele-specific products through redox
      tags in close proximity to the electrode. Such a unique biphasic architecture
      provided a universal methodology for incorporating enzymatic discrimination
      reactions in electrochemical genotyping with desirable reproducibility, high
      efficiency and no interferences from interficial steric hindrance. The developed
      technique was demonstrated to show intrinsic high sensitivity for direct genomic
      analysis, and excellent specificity with discriminativity of single nucleotide
      variations.

PMID- 19178279
TI  - Disulfide-linked, gold nanoparticle based reagent for detecting small molecular
      weight thiols.
AB  - Disulfide-linked gold nanoparticles (AuNP) were synthesized by reacting
      dithiobis[succinimidylpropionate] (DSP) coated nanoparticles with glutathione
      disulfide. AuNP-cross-linking was monitored by the red shift and broadening of
      the AuNP's localized surface plasmon absorption resonance (LSPR) spectrum. The
      exposure of the disulfide-linked AuNPs to a variety of free thiols with
      systematically varying molecular weight revealed a AuNP-disulfide stability to
      reduction by thiols up to a critical molecular weight, M(c), of >300 Da thus
      making the disulfide-linked AuNP the first reagent that can discriminate thiols
      based on their size.

PMID- 19178280
TI  - Highly uniaxial orientation in oligo(p-phenylenevinylene) films induced during
      wet-coating process.
AB  - Highly uniaxial alignment of pi-conjugated oligo(p-phenylenevinylene)s was
      spontaneously achieved in the as-cast films by simply spin-coating the solution
      onto mechanically rubbed polymer alignment layers such as poly(3,4
      ethylenedioxythiophene)/poly(styrene sulfonic acid) (PEDOT:PSS) film, resulting
      in a high dichroic ratio (A(//)/A(perpendicular)) of 41.0 and an order parameter
      ([A(//) - A(perpendicular)]/[A(//) + 2A(perpendicular)]) of 0.93 estimated from
      the polarized absorption spectra of the films, and its application to organic
      photovoltaic devices was also demonstrated to achieve a high anisotropy in
      photosensitivity.

PMID- 19178281
TI  - Fruit quality and bioactive compounds with antioxidant activity of tomatoes grown
      on-farm: comparison of organic and conventional management systems.
AB  - Replicated field trials at three matched farm pairs in southern and central
      Taiwan were established in October 2004 and 2005 to compare fruit quality and
      nutritional parameters of tomatoes grown on-farm under organic versus
      conventional management systems in tropical and subtropical environments. Two
      processing tomato varieties were evaluated using a randomized complete block
      design at each of the farms. Aggregation of farms by type (organic vs
      conventional) across two years resulted in no significant differences between
      organic and conventional farming systems for all tomato fruit parameters
      measured, including quality (pH, soluble solids, acidity, and color), content of
      bioactive compounds with antioxidant activity (beta-carotene, lycopene, ascorbic
      acid, and total phenolics), and antioxidant activity. This study indicated no
      consistent effect of the farming system on tomato fruit parameters. Farm
      management skills combined with site-specific effects contributed to high
      lycopene levels, and the choice of variety significantly influenced the content
      of bioactive compounds, particularly ascorbic acid and total phenolics.

PMID- 19178282
TI  - Influence of olives' storage conditions on the formation of volatile phenols and
      their role in off-odor formation in the oil.
AB  - Volatile phenols are spoilage compounds of many foods, which have also been
      detected in the volatile fraction of defective virgin olive oils (VOOs). However,
      their formation in olive fruits or VOOs, as well as the factors affecting their
      production, has yet to be elucidated. In the present study, the evolution of
      volatile phenols was monitored for the first time in VOOs obtained from olives
      stored during different periods under two different conditions of limited
      aerobiosis. Moreover, their odor activity values (OAVs) in VOO samples were
      calculated as a first assessment of their sensory importance, and the
      microbiological profile of the olives' surface was evaluated at each sampling
      point in order to clarify the possible causes of volatile phenols formation.
      Although volatile phenols seem to acquire their sensory significance at advanced
      stages of olives' alteration, they were significantly correlated to the time of
      olives' storage and in accordance with sensory evaluation, indicating that they
      could be considered as analytical indices of olive fruits' degradation during
      storage, likely reflecting the microbiological activity.

PMID- 19178283
TI  - Rapid and simultaneous determination of lycopene and beta-carotene contents in
      tomato juice by infrared spectroscopy.
AB  - The rapid quantification of lycopene and beta-carotene in tomato juices by
      attenuated total reflectance (ATR) infrared spectroscopy combined with
      multivariate analysis was evaluated. Two sample preparation methods were
      compared: a direct measurement of the tomato paste and an extraction method using
      hexane to isolate carotenoids. HPLC was used as the reference method. Cross
      validated (leave-one-out) partial least-squares regression (PLSR) was used to
      create calibration models to predict these phytonutrient concentrations in blind
      test samples. The infrared spectra showed unique marker bands at 957 and 968 cm(
      1) for lycopene and beta-carotene, respectively. Multivariate analysis of the
      infrared spectral data gave correlation coefficients (r values) of >0.9 between
      the ATR-IR predicted and HPLC reference values, and standard errors of cross
      validation (SECV) of 0.5 and 0.04 mg/100 g of juice for lycopene and beta
      carotene, respectively. ATR-IR could provide the tomato industry with a simple,
      rapid, and high-throughput technique for the determination of tomato quality.

PMID- 19178284
TI  - Runoff and leaching of metolachlor from Mississippi River alluvial soil during
      seasons of average and below-average rainfall.
AB  - The movement of the herbicide metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N
      (2-methoxy-1-methylethyl)acetamide] via runoff and leaching from 0.21 ha plots
      planted to corn on Mississippi River alluvial soil (Commerce silt loam) was
      measured for a 6-year period, 1995-2000. The first three years received normal
      rainfall (30 year average); the second three years experienced reduced rainfall.
      The 4-month periods prior to application plus the following 4 months after
      application were characterized by 1039 +/- 148 mm of rainfall for 1995-1997 and
      by 674 +/- 108 mm for 1998-2000. During the normal rainfall years 216 +/- 150 mm
      of runoff occurred during the study seasons (4 months following herbicide
      application), accompanied by 76.9 +/- 38.9 mm of leachate. For the low-rainfall
      years these amounts were 16.2 +/- 18.2 mm of runoff (92% less than the normal
      years) and 45.1 +/- 25.5 mm of leachate (41% less than the normal seasons).
      Runoff of metolachlor during the normal-rainfall seasons was 4.5-6.1% of
      application, whereas leaching was 0.10-0.18%. For the below-normal periods, these
      losses were 0.07-0.37% of application in runoff and 0.22-0.27% in leachate. When
      averages over the three normal and the three less-than-normal seasons were taken,
      a 35% reduction in rainfall was characterized by a 97% reduction in runoff loss
      and a 71% increase in leachate loss of metolachlor on a percent of application
      basis. The data indicate an increase in preferential flow in the leaching
      movement of metolachlor from the surface soil layer during the reduced rainfall
      periods. Even with increased preferential flow through the soil during the below
      average rainfall seasons, leachate loss (percent of application) of the herbicide
      remained below 0.3%. Compared to the average rainfall seasons of 1995-1997, the
      below-normal seasons of 1998-2000 were characterized by a 79% reduction in total
      runoff and leachate flow and by a 93% reduction in corresponding metolachlor
      movement via these routes. An added observation in the study was that neither
      runoff of rainfall nor runoff loss of metolachlor was influenced by the presence
      of subsurface drains, compared to the results from plots without such drains that
      were described in an earlier paper.

PMID- 19178286
TI  - Feasibility of serodiagnosis of ovarian cancer by mass spectrometry.
AB  - The emergence of new biological disease markers from mass spectrometric studies
      of serum proteomes has been quite limited. There are challenges regarding the
      analytical and statistical procedures, preanalytical variability, and study
      designs. In this serological study of ovarian cancer, we apply classification
      methods in a strictly designed study with standardized sample collection
      procedures. A total of 265 sera from women admitted with symptoms of a pelvic
      mass were used for model building. We developed a rigorous approach for building
      classification models suitable for the highly multivariate data and illustrate
      how to evaluate and ensure data quality and optimize data preprocessing and data
      reduction. We document time dependent changes in peak profiles up to 15 months
      after sampling even when storing samples at -20 degrees C. The developed
      classification model was validated using completely independent samples, and a
      cross validation procedure which we call cross model validation was applied to
      get realistic performance values. The best models were able to classify with 79%
      specificity and 56% sensitivity, i.e., an analytical accuracy of 68%. However,
      the existing serum marker (CA-125) alone gave a better analytical accuracy (81%)
      in the same sample set. Also, the combination of mass spectrometric data and
      levels of CA-125 data did not improve the predictive performance of models. In
      conclusion, proteomic approaches to biomarker discovery are not necessarily
      yielding straightforward diagnostic leads but lay the foundation for more work.

PMID- 19178285
TI  - High-sensitivity nanoLC-MS/MS analysis of urinary desmosine and isodesmosine.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by the degradation
      of elastin, the major insoluble protein of lung tissues. The degradation of
      elastin gives rise to desmosine (DES) and isodesmosine (IDES), two major urinary
      products typified by a hydrophilic pyridinium-based cross-linker structure. A
      high sensitivity method based on nanoflow liquid chromatography tandem mass
      spectrometry with multiple reaction monitoring was developed for the analysis of
      urinary DES and IDES. The analytes were derivatized with propionic anhydride and
      deuterated DES (D(4)-DES) was used as an internal standard. This method enables
      the quantification of DES and IDES in as little as 50 microL of urine and
      provides a detection limit of 0.10 ng/mL (0.95 fmol on-column). We report the
      analysis of DES and IDES in a cohort of 40 urine specimens from four groups of
      individuals: (a) COPD rapid decliners (11.8 +/- 3.7 ng/mg creatine (crea)), (b)
      COPD slow decliners (16.0 +/- 3.1 ng/mg crea), (c) healthy smokers (13.2 +/- 1.9
      ng/mg crea), and (d) healthy nonsmokers (14.9 +/- 2.9 ng/mg crea). Our analysis
      reveals a statistically significant decrease in the level of urinary DES and IDES
      in COPD rapid decliner patients compared to healthy nonsmoker controls and COPD
      slow decliner patients. This methodology may be useful for monitoring DES and
      IDES levels in well controlled animal models for COPD or for longitudinal studies
      in COPD patients.

PMID- 19178287
TI  - Oligosaccharide promotes bioavailability of a water-soluble flavonoid glycoside,
      alpha G-rutin, in rats.
AB  - This study examined the effects of a nondigestible saccharide, difructose
      anhydride (DFA) III, and fructooligosaccharides (FOS) on the intestinal
      absorption and metabolism of alpha G-rutin, a quercetin glycoside in rats during
      a 2 week feeding period with diets containing 1% alpha G-rutin with or without
      1.5 or 3% DFAIII and FOS. Blood concentrations and urinary excretion of quercetin
      derivatives were largely and dose-dependently increased during the test period
      with feeding DFA III and FOS. The amounts of quercetin derivatives in the cecal
      contents and feces were also much higher in both saccharide groups than in the
      control group. The degradation rate of aglycone, estimated by differences between
      ingestion and sum of fecal and urinary excretion, were suppressed in the both
      saccharide groups. Cecal fermentation was dose-dependently modified by the
      oligosaccharides. It was concluded that suppression of degrading quercetin
      aglycone in the large intestine has a major role for increasing alpha G-rutin
      bioavailability by DFA III and FOS feedings.

PMID- 19178289
TI  - Derivatives of 5-nitro-furan-2-carboxylic acid carbamoylmethyl ester inhibit
      RNase H activity associated with HIV-1 reverse transcriptase.
AB  - The RNase H activity associated with human immunodeficiency virus type 1 (HIV-1)
      is an attractive target for an antiretroviral drug development. We screened 20000
      small-molecular-weight compounds for RNase H inhibitors and identified a novel
      RNase H-inhibiting structure characterized by a 5-nitro-furan-2-carboxylic acid
      carbamoylmethyl ester (NACME) moiety. Two NACME derivatives, 5-nitro-furan-2
      carboxylic acid adamantan-1-carbamoylmethyl ester (compound 1) and 5-nitro-furan
      2-carboxylic acid [[4-(4-bromo-phenyl)-thiazol-2-yl]-(tetrahydro-furan-2
      ylmethyl)-carbamoyl]-methyl ester (compound 2), effectively blocked HIV-1 and MLV
      RT-associated RNase H activities with IC(50)s of 3-30 microM but had little
      effect on bacterial RNase H activity in vitro. Additionally, 20-25 microM
      compound 2 effectively inhibited HIV-1 replication. An in silico docking
      simulation indicated that the conserved His539 residue, and two metal ions in the
      RNase H catalytic center are involved in RNase H inhibition by NACME derivatives.
      Taken together, these data suggest that NACME derivatives may be potent lead
      compounds for development of a novel class of antiretroviral drugs.

PMID- 19178290
TI  - Microwave-assisted synthesis of 9-arylpurines.

PMID- 19178288
TI  - Free-solution label-free detection of alpha-crystallin chaperone interactions by
      back-scattering interferometry.
AB  - We report the quantitative, label-free analysis of protein-protein interactions
      in free solution within picoliter volumes using backscatter interferometry (BSI).
      Changes in the refractive index are measured for solutions introduced on a PDMS
      microchip allowing determination of forward and reverse rate constants for two
      mode binding. Time-dependent BSI traces are directly fit using a global analysis
      approach to characterize the interaction of the small heat-shock protein alpha
      Crystallin with two substrates: destabilized mutants of T4 lysozyme and the in
      vivo target betaB1-Crystallin. The results recapitulate the selectivity of alphaB
      Crystallin differentially binding T4L mutants according to their free energies of
      unfolding. Furthermore, we demonstrate that an alphaA-Crystallin mutant linked to
      hereditary cataract has activated binding to betaB1-Crystallin. Binding isotherms
      obtained from steady-state values of the BSI signal yielded meaningful
      dissociation constants and establishes BSI as a novel tool for the rapid
      identification of molecular partners using exceedingly small sample quantities
      under physiological conditions. This work demonstrates that BSI can be extended
      to screen libraries of disease-related mutants to quantify changes in affinity
      and/or kinetics of binding.

PMID- 19178291
TI  - Cyclodextrin inclusion complex formation and solid-state characterization of the
      natural antioxidants alpha-tocopherol and quercetin.
AB  - Cyclodextrin (CD) complexation procedures are relatively simple processes, but
      these techniques often require very specific conditions for each individual guest
      molecule. Variations of the coprecipitation from aqueous solution technique were
      optimized for the CD complexation of the natural antioxidants alpha-tocopherol
      and quercetin. Solid inclusion complex products of alpha-tocopherol/beta-CD and
      quercetin/gamma-CD had molar ratios of 1.7:1, which were equivalent to 18.1%
      (w/w) alpha-tocopherol and 13.0% (w/w) quercetin. The molar reactant ratios of
      CD/antioxidant were optimized at 8:1 to improve the yield of complexation. The
      product yields of alpha-tocopherol/beta-CD and quercetin/gamma-CD complexes from
      their individual reactants were calculated as 24 and 21% (w/w), respectively.
      ATR/FT-IR, 13C CP/MAS NMR, TGA, and DSC provided evidence of antioxidant
      interaction with CD at the molecular level, which indicated true CD inclusion
      complexation in the solid state. Natural antioxidant/CD inclusion complexes may
      serve as novel additives in controlled-release active packaging to extend the
      oxidative stability of foods.

PMID- 19178292
TI  - Reactions of functionalized sulfonamides: application to lowering the
      lipophilicity of cytosolic phospholipase A2alpha inhibitors.
AB  - The cPLA(2)alpha inhibitors we reported earlier were potent in both isolated
      enzyme and rat whole blood assays but have high plogD(7.4). To address these
      issues, reactions of electrophilic sulfonamides 9-12 were employed to incorporate
      various heterocyclic or heteroatom-based reagents into cPLA(2)alpha inhibitors.
      For example, reactions of 9 with sulfur nucleophiles such as thiophenol allowed
      rapid assembly of thioether analogues that were converted into the corresponding
      sulfoxides to afford less lipophilic derivatives. Reactions of 10 and 11 with
      various nitrogen nucleophiles, including aromatic heterocycles and aliphatic
      amines, provided an efficient way to introduce polarity into cPLA(2)alpha
      inhibitors. Finally, we report the first application of (2
      formylphenyl)methanesulfonyl chloride, 13. Reductive amination of 2
      formylphenylmethane sulfonamides allowed the introduction of various nitrogen
      nucleophiles. Several inhibitors obtained herein have plogD(7.4) values 3-4 units
      lower than previously synthesized compounds and yet maintain in vitro potency.

PMID- 19178294
TI  - Total synthesis of valerenic acid, a potent GABAA receptor modulator.
AB  - The first total synthesis of the sesquiterpenoid valerenic acid, a constituent of
      Valeriana officinalis, is described. The compound is a potent modulator of the
      GABA(A) receptor and may thus be useful in the treatment of various dysfunctions
      of the central nervous system. The synthesis is enantio-, diastereo-, and
      regiocontrolled and utilizes an enyne-RCM, a metal-coordinated Diels-Alder
      reaction, a hydroxy-directed Crabtree hydrogenation, and a Negishi methylation as
      key steps.

PMID- 19178295
TI  - Reversible switching of magnetism in thiolate-protected Au25 superatoms.
AB  - We report reversible switching of paramagnetism in a well-defined gold
      nanoparticle system consisting of atomically monodisperse nanoparticles
      containing 25 gold atoms protected by 18 thiolates [abbreviated as
      Au(25)(SR)(18)]. The magnetism in these nanoparticles can be switched on or off
      by precisely controlling the charge state of the nanoparticle, that is, the
      magnetic state of the Au(25)(SR)(18) nanoparticles is charge-neutral while the
      nonmagnetic state is an anionic form of the particle. Electron paramagnetic
      resonance (EPR) spectroscopy measurements establish that the magnetic state of
      the Au(25)(SR)(18) nanoparticles possess one unpaired spin per particle. EPR
      studies also imply an unusual electronic structure of the Au(25)(SR)(18)
      nanoparticle. Density functional theory calculations coupled with the experiments
      successfully explain the origin of the observed magnetism in a Au(25)(SR)(18)
      nanoparticle as arising from one unpaired spin having distinct P-like character
      and delocalized among the icosahedral Au(13) core of the particle in the highest
      occupied molecular orbital. The results suggest that the Au(25)(SR)(18)
      nanoparticles are best considered as ligand-protected superatoms.

PMID- 19178296
TI  - Alpha-mangostin suppresses PC-3 human prostate carcinoma cell metastasis by
      inhibiting matrix metalloproteinase-2/9 and urokinase-plasminogen expression
      through the JNK signaling pathway.
AB  - Alpha-mangostin, a component of Garcinia mangostana Linn, is a xanthone
      derivative shown to have antioxidant and anticarcinogen properties. In this
      study, we first report the antimetastatic effect of alpha-mangostin in the human
      prostate carcinoma cell line PC-3. The results show that alpha-mangostin
      exhibited an inhibitory effect on the abilities of adhesion, migration, and
      invasion by cell-matrix adhesion assay, wound healing assay, and Boyden chamber
      assay. In the cancer cell metastasis process, matrix degrading proteinases are
      required. Results from zymography showed that alpha-mangostin treatment could
      decrease the expressions of matrix metalloproteinase-2 (MMP-2), matrix
      metalloproteinase-9 (MMP-9), and urokinase-plasminogen activator (u-PA) in a
      concentration-dependent manner. Moreover, alpha-mangostin also exerted an
      inhibitory effect on phosphorylation of c-Jun N-terminal kinase 1 and 2 (JNK1/2)
      and inhibition of activation of nuclear factor kappa B (NF-kappaB), c-Fos, and c
      Jun. Furthermore, the treatment of inhibitors specific for JNK (SP600125) to PC-3
      cells could result in a reduced expression of MMP-2, MMP-9, and u-PA. These
      results demonstrated that alpha-mangostin could mediate PC-3 cells metastasis by
      reduction of MMP-2, MMP-9, and u-PA expression through the suppression of the
      JNK1/2 signaling pathway and inhibition of NF-kappaB and AP-1 binding activity.
      These findings proved that alpha-mangostin might be offered further application
      as an antimetastatic agent.

PMID- 19178297
TI  - Gold nanoparticles surface plasmon field effects on the proton pump process of
      the bacteriorhodopsin photosynthesis.
AB  - The rate of the proton pump of bacteriorhodopsin photosynthetic system is
      examined in the presence of a gold nanorod plasmon field. It is found that while
      the rate of the proton dissociation from the protonated Schiff base is not
      affected, the rate of its reprotonation increases. These results are
      qualitatively discussed in terms of several possible mechanisms.

PMID- 19178299
TI  - Ribosomal proteins of Deinococcus radiodurans: their solvent accessibility and
      reactivity.
AB  - The structure of proteins in native ribosomes from Deinococcus radiodurans R1 was
      probed by S-methylthioacetimidate (SMTA) modification of amino groups. The extent
      of protein labeling was quantified using top down methods, and modified positions
      were identified using bottom up experiments. Each protein's reactivity was
      predicted by examination of the crystal structures of the D. radiodurans 50S
      subunit and the T. thermophilus HB8 30S subunit. The close phylogenetic relation
      between D. radiodurans and T. thermophilus allowed the evaluation of D.
      radiodurans small subunit protein reactivity by alignment of homologous
      sequences. As a result, we were able to observe and characterize the reactivity
      of all of D. radiodurans ribosomal proteins. The extent of protein amidination
      was well correlated with the solvent-exposed surface area of each protein and
      even better correlated with the number of visible lysine residues. Lysine
      residues that are in close contact with rRNA structural features or buried in
      protein tertiary structure are nonreactive with SMTA, while those that are
      surface exposed are modified. Crystallographic disorder and post-translational
      modifications lead to differences between the observed and predicted extents of
      reactivity. Comparison of unmodified and disassembled amidinated protein mixtures
      also shows great promise for the quality control of the proteomic sequences and
      has facilitated the identification of four sequencing errors in the ribosomal
      proteome of D. radiodurans R1.

PMID- 19178300
TI  - Quantitative phosphoproteomics of tomato mounting a hypersensitive response
      reveals a swift suppression of photosynthetic activity and a differential role
      for hsp90 isoforms.
AB  - An important mechanism by which plants defend themselves against pathogens is the
      rapid execution of a hypersensitive response (HR). Tomato plants containing the
      Cf-4 resistance gene mount an HR that relies on the activation of phosphorylation
      cascades, when challenged with the Avr4 elicitor secreted by the pathogenic
      fungus Cladosporium fulvum. Phosphopeptides were isolated from tomato seedlings
      expressing both Cf-4 and Avr4 using titanium dioxide columns and LC-MS/MS
      analysis led to the identification of 50 phosphoproteins, most of which have not
      been described in tomato before. Phosphopeptides were quantified using a label
      free approach based on the MS peak areas. We identified 12 phosphopeptides for
      which the abundance changed upon HR initiation, as compared to control seedlings.
      Our results suggest that photosynthetic activity is specifically suppressed in a
      phosphorylation-dependent way during the very early stages of HR development. In
      addition, phosphopeptides originating from four Hsp90 isoforms exhibited altered
      abundances in Cf-4/Avr4 seedlings compared to control seedlings, suggesting that
      the isoforms of this chaperone protein have a different function in defense
      signaling. We show that label-free relative quantification of the phosphoproteome
      of complex samples is feasible, allowing extension of our knowledge on the
      general physiology and defense signaling of plants mounting the HR.

PMID- 19178301
TI  - Strategy for glycoproteomics: identification of glyco-alteration using multiple
      glycan profiling tools.
AB  - Glycan alterations of proteins, a common feature of cancer cells, are associated
      with carcinogenesis, invasion and metastasis. Glycomics, the study of glycans and
      glycan-binding proteins in various biological systems, is an emerging field in
      the postgenome and postproteomics era. However, systematic and robust strategies
      for glycomics are still not fully established because the structural analysis of
      glycans, which comprise different patterns of branching, various possible linkage
      positions as well as monomer anomericity, is technically difficult. Here, we
      introduce a new strategy for glyco-alteration analysis of glycoproteins by using
      multiple glycan profiling tools. To understand glycan alterations of proteins by
      correlating the glycosyltransferase expression profile with the actual glycan
      structure, we systematically used three glycan profiling tools: (1) multiplex
      quantitative PCR (qPCR) array format for profiling the expression pattern of
      glycogenes, (2) lectin microarray as a multiplex glycan-lectin interaction
      analysis system for profiling either a pool of cell glycoproteins or a target
      glycoprotein, and (3) tandem mass spectrometry for identifying the glycan
      structure connected to a target glycoprotein. Using our system, we successfully
      identified glycan alterations on alpha-fetoprotein (AFP), including a novel
      LacdiNAc structure in addition to previously reported alterations such as
      alpha1,6 fucosylation.

PMID- 19178302
TI  - Transcription factor TBX1 overexpression induces downregulation of proteins
      involved in retinoic acid metabolism: a comparative proteomic analysis.
AB  - TBX1 haploinsufficiency is considered a major contributor to the
      del22q11.2/DiGeorge syndrome (DGS) phenotype. We have used proteomic tools to
      look at all the major proteins involved in the TBX1-mediated pathways in an
      attempt to better understand the molecular interactions instrumental to its
      cellular functions. We found more than 90 proteins that could be targeted by TBX1
      through different mechanisms. The most interesting observation is that
      overexpression of TBX1 results in down-regulation of two proteins involved in
      retinoic acid metabolism.

PMID- 19178329
TI  - A conversation with some postdoctorals.

PMID- 19178303
TI  - Automated 2D peptide separation on a 1D nano-LC-MS system.
AB  - Given the complexity of the mammalian proteome, high-resolution separation
      technologies are required to achieve comprehensive proteome coverage and to
      enhance the detection of low-abundance proteins. Among several technologies,
      Multidimensional Protein Identification Technology (MudPIT) enables the on-line
      separation of highly complex peptide mixtures directly coupled with mass
      spectrometry-based identification. Here, we present a variation of the
      traditional MudPIT protocol, combining highly sensitive chromatography using a
      nanoflow liquid chromatography system (nano-LC) with a two-dimensional precolumn
      in a vented column setup. When compared to the traditional MudPIT approach, this
      nanoflow variation demonstrated better first-phase separation leading to more
      proteins being characterized while using rather simple instrumentation and a
      protocol that requires less time and very little technical expertise to perform.

PMID- 19178334
TI  - Using laser-induced acoustic desorption/electrospray ionization mass spectrometry
      to characterize small organic and large biological compounds in the solid state
      and in solution under ambient conditions.
AB  - We have coupled laser-induced acoustic desorption (LIAD) with electrospray
      ionization (ESI) mass spectrometry (LIAD/ESI/MS) to characterize molecules in the
      solid state and in solution under ambient conditions. To perform an LIAD/ESI
      analysis, the sample droplet is deposited on the surface of a thin aluminum foil
      by a micropipette; the rear side of the foil with the sample spot is then
      irradiated with a pulse from a Nd:YAG IR laser. The resulting shockwave and heat
      cause the sample on the rear side to change from the condensed phase to the gas
      phase. The desorbed species then move upward to enter an ESI plume to react with
      charged solvent species (methanol- and water-related ions and droplets), forming
      singly or multiply charged analyte ions. A quadrupole/time-of-flight (Q-TOF) mass
      analyzer attached to the LIAD/ESI source detects the analyte ions to obtain an
      ESI-like mass spectrum. Both small organic and large biological compounds
      (including amino acids, peptides, and proteins) were successfully ionized and
      detected by the LIAD/ESI/MS system. Although native and denatured myoglobin ions
      were both detected from a liquid sample solution, only the denatured myoglobin
      ions were detected from a dried sample.

PMID- 19178335
TI  - High-speed shear-driven flows through microstructured 1D-nanochannels.
AB  - A new flow type for the conduction of rapid chromatographic and macro-molecular
      separations in 1D nanochannels is reported. It combines the pressure-drop-less
      operation of shear-driven flows with the meandering flow paths that are present
      in ordered arrays of micro- and nanopillars. Similar to shear-driven flows in
      open channels, the achievable fluid velocity is quasi unlimited and is not
      affected by a pressure- or voltage-drop, while the axial dispersion in the
      microstructured pillar arrays remains surprisingly low. In the present paper, we
      report on a series of flow resistance and band broadening experiments that have
      been conducted to characterize the hydrodynamical properties of this new flow
      type. In addition, theoretical computational fluid dynamics (CFD) simulations
      have been performed to explain the observations. Good agreement between theory
      and experiment was obtained.

PMID- 19178336
TI  - Microwave heating in preparation of magnetic molecularly imprinted polymer beads
      for trace triazines analysis in complicated samples.
AB  - The use of microwave heating for preparation in organic synthesis has been
      accepted as an effective technique in synthesis due to the significant advantages
      over the conventional method. In the present work, microwave heating was applied
      to the preparation of atrazine (template molecule) magnetic molecularly imprinted
      polymer (mag-MIP) beads by suspension polymerization. The term of the
      polymerization was dramatically shortened by using microwave heating in
      polymerization, which was less than (1)/(10) that by conventional heating. The
      resultant polymers incorporating molecular recognition and magnetic separation
      can provide a highly selective material for trace analysis in complicated
      samples. The mag-MIP beads were demonstrated with a narrow diameter distribution
      (80-250 microm) and cross-linking, spherical shape, and porous morphologies and
      exhibited magnetic property (M(s) = 0.491 emicro/g) and thermal stability under
      260 degrees C. An improvement of imprinted efficiency is obtained in comparison
      to the mag-MIP beads prepared by conventional heating. A method for the
      determination of triazines in complicated samples by the mag-MIP beads extraction
      coupled with high-performance liquid chromatography (HPLC) was developed. The
      results indicated that the mag-MIP beads can be favorably used for the extraction
      of the triazines in spiked soil, soybean, lettuce, and millet samples. The reused
      beads displayed a long-term stability after undergoing extraction of 100 times.

PMID- 19178337
TI  - Three-dimensional in situ temperature measurement in microsystems using Brownian
      motion of nanoparticles.
AB  - We report an in situ method for three-dimensionally resolved temperature
      measurement in microsystems. The temperature of the surrounding fluid is
      correlated from Brownian diffusion of suspended nanoparticles. We use video
      microscopy in combination with image analysis software to selectively track
      nanoparticles in the focal plane. This method is superior with regards to
      reproducibility and reduced systematic errors since measuring Brownian
      diffusivity does not rely on fluorescence intensity or lifetime of fluorophores.
      The efficacy of the method is demonstrated by measuring spatial temperature
      profiles in various microfluidic devices that generate temperature gradients and
      by comparing these results with numerical simulations. We show that the method is
      accurate and can be used to extract spatial temperature variations in three
      dimensions. Compared to conventional methods that require expensive multiphoton
      optical sectioning setups, this technique is simple and inexpensive. In addition,
      we demonstrate the capability of this method as an in situ tool for
      simultaneously observing live cells under the microscope and monitoring the local
      temperature of the cell medium without biochemical interference, which is crucial
      for quantitative studies of cells in microfluidic devices.

PMID- 19178338
TI  - Off-line two-dimensional liquid chromatography with maximized sample loading to
      reversed-phase liquid chromatography-electrospray ionization tandem mass
      spectrometry for shotgun proteome analysis.
AB  - We demonstrate a strategy of maximizing the performance of reversed-phase (RP)
      liquid chromatography (LC) tandem mass spectrometry (MS/MS) for efficient shotgun
      proteome analysis by optimizing the sample loading to the instrument in an off
      line two-dimensional (2D) LC tandem MS platform. To determine the quantity of
      peptides present in a proteome digest or fractionated peptides from strong-cation
      exchange (SCX) separation, an automated system based on RPLC with a rapid step
      solvent gradient for peptide elution and ultraviolet (UV) detection was
      developed. This system also allowed the purification of the peptides by removing
      salts and other impurities present in a sample. It was found that controlling the
      amount of peptides injected into a RPLC MS/MS system was critical to achieve the
      maximum efficiency in peptide and protein identification. With the use of off
      line 2D-LC-MS/MS, peptide fractions from the first dimension of separation were
      desalted and quantified, followed by injecting the optimal amount of the sample
      into RPLC-MS/MS for peptide sequencing. The application of this strategy was
      demonstrated in the proteome profiling of breast cancer MCF-7 cells. From the
      analysis of 28 SCX fractions with each injecting 1 microg of sample into a 75 mum
      x 100 mm C18 column interfaced to a quadrupole/time-of-flight mass spectrometer,
      a total of 2362 unique proteins or protein groups were identified with a false
      positive peptide identification rate of 0.19%, as determined by target-decoy
      proteome sequence searches. Replicate 2 h runs of individual fractions with the
      exclusion of precursor ions of peptides already identified in the first runs
      resulted in the identification of an additional 549 unique proteins or protein
      groups with a false positive identification rate of 0.60%. This example
      illustrated that off-line 2D-LC-MS/MS, with maximal sample injection to the RPLC
      MS, is an effective method for shotgun proteome analysis. Finally, the advantages
      and limitations of this method, compared to other methods, are discussed.

PMID- 19178339
TI  - Quantification of technetium-99 in complex groundwater matrixes using a
      radiometric preconcentrating minicolumn sensor in an equilibration-based sensing
      approach.
AB  - A preconcentrating minicolumn sensor for technetium-99 detection in water
      consists of a packed bed containing a mixture of anion-exchange resin and
      scintillating plastic beads. The column materials are contained in a transparent
      plastic flow cell placed between two photomultiplier tubes for radiometric
      detection. Upon retention of pertechnetate anions, the radioactive decay of Tc-99
      results in detectable scintillation pulses that are counted in coincidence. In
      equilibration-based sensing mode, the sample is pumped through the packed bed
      until complete chromatographic equilibrium is achieved between the activity
      concentration in the water sample and the concentration on the anion-exchange
      resin. The analytical signal is the observed steady-state count rate at
      equilibrium. The sensitivity is related to a measurement efficiency parameter
      that is the product of the retention volume and the absolute radiometric
      detection efficiency. This sensor can readily detect pertechnetate to levels 10
      times below the drinking water standard of 0.033 Bq/mL. The potential for other
      anions in natural groundwater and contaminated groundwater plumes to interfere
      with pertechnetate detection and quantification has been examined in detail, with
      reference to the groundwater chemistry at the Hanford site in Washington state.
      Individual anions such as nitrate, carbonate, chloride, and iodide, at natural or
      elevated concentrations, do not interfere significantly with pertechnetate uptake
      on the anion-exchange resin. Elevated chromate or sulfate anion concentrations
      can interfere with pertechnetate uptake by the resin, but only at levels
      substantially higher than typical concentrations in groundwater or contamination
      plumes. Nevertheless, elevated anion concentrations may reduce pertechnetate
      uptake and sensitivity of the sensor when present in combination. Chromate is
      retained on the anion-exchange resin from water at parts-per-billion levels,
      leading to an orange stain that interferes with pertechnetate detection by the
      absorption of scintillation light pulses (color quench). Radioactivity from
      radioiodine, tritium, and uranium is not expected to create a significant
      positive bias in groundwater analyses. A method of automated fluidic standard
      addition is demonstrated that corrects for matrix interferences leading to
      accurate analyses over a wide range of groundwater compositions. This method is
      developed for automated groundwater monitoring applications.

PMID- 19178340
TI  - Elucidating the structure of cyclotides by partial acid hydrolysis and LC-MS/MS
      analysis.
AB  - We describe here a rapid method to determine the cyclic structure and disulfide
      linkages of highly stable cyclotides via a combination of flash partial acid
      hydrolysis, LC-MS/MS, and computational tools. Briefly, a mixture of closely
      related cyclotides, kalata B1 and varv A purified from Viola yedoensis was
      partially hydrolyzed in 2 M HCl for 5 min by microwave-assisted hydrolysis or for
      30 min in an autoclave oven (121 degrees C and 15 psi). The partially hydrolyzed
      peptide mixture was then subjected to LC-MS/MS analysis, with the disulfide
      linked-peptides fragmented by collision activated dissociation (CAD). A computer
      program written in-house (available for download at
      http://proteomics.sbs.ntu.edu.sg/cyclotide_SS ) was used for interpreting LC
      MS/MS spectra and assigning the disulfide bonds. Time-point analysis of single
      disulfide fragments revealed that nonrandom acid catalyzed fragmentation mostly
      occurred at the turns which are solvent-exposed and often contain side chain
      functionalized amino acids such as Asx/Glx and Ser/Thr. In particular, the most
      susceptible bond for acid hydrolysis in kalata B1 and varv A was found to be the
      highly conserved N25-G26 which is also the head-to-tail ligation site of the
      linear precursor proteins, indicating that formation of the three disulfide bonds
      might precede cyclic structure closure by N25-G26 ligation. This observation is
      consistent with the recent report that the N25-G26 bond formation is the last
      step in the cyclotide biosynthetic pathway. The process demonstrated here can
      potentially be a high throughput method that is generally applicable to determine
      disulfide bonds of other relatively low-abundance cyclotides.

PMID- 19178341
TI  - Regenerable tethered bilayer lipid membrane arrays for multiplexed label-free
      analysis of lipid-protein interactions on poly(dimethylsiloxane) microchips using
      SPR imaging.
AB  - We report a microfabrication approach to generate well-defined, addressable, and
      regenerable lipid membrane arrays in poly(dimethylsiloxane) (PDMS) microchips for
      label-free analysis of lipid-protein interactions with surface plasmon resonance
      imaging (SPRi). The multiplexed detection is demonstrated with a tethered bilayer
      membrane array built in parallel microchannels. These channels allow multiple
      measurements to be carried out simultaneously, showing low deviations for element
      to-element variation in quantifiable signal. Lipid-conjugated receptors were
      utilized as model systems for protein binding analysis, and the feasibility of
      regenerating the tethering sublayer after binding was investigated. The results
      show that the lipid membrane can be removed effectively by nonionic surfactant
      Triton X-100. The small variance in SPR signal for the buildup process, i.e., <4%
      RSD for 3 cycles of detection, removal, and regeneration, indicates the sensing
      interface is highly reproducible. A calibration curve was obtained for cholera
      toxin using the monosialoganglioside (GM1) receptor, displaying a linear
      relationship in the 25 to 175 microg/mL range with a limit of detection of 260
      nM. In addition, interaction of a phosphatidylinositol (PIP) with its binding
      protein and biotin/avidin interactions were employed for array measurements. To
      further enhance the SPR detection signal, a layer-by-layer amplification strategy
      was demonstrated that uses biotinylated antibody, NeutrAvidin and biotinylated
      anti-avidin, and the signal for protein binding on the membrane increased by
      400%. The tethered membrane array technology, in combination with SPRi, offers an
      attractive platform for studies of membrane proteins, and can also find a range
      of applications for rapid screening of drug candidates interacting with proteins
      embedded in the near-native environment.

PMID- 19178342
TI  - Microfluidic perfusion system for automated delivery of temporal gradients to
      islets of Langerhans.
AB  - A microfluidic perfusion system was developed for automated delivery of stimulant
      waveforms to cells within the device. The 3-layer glass/polymer device contained
      two pneumatic pumps, a 12 cm mixing channel, and a 0.2 microL cell chamber. By
      altering the flow rate ratio of the pumps, a series of output concentrations
      could be produced while a constant 1.43 +/- 0.07 microL/min flow rate was
      maintained. The output concentrations could be changed in time producing step
      gradients and other waveforms, such as sine and triangle waves, at different
      amplitudes and frequencies. Waveforms were analyzed by comparing the amplitude of
      output waveforms to the amplitude of theoretical waveforms. Below a frequency of
      0.0098 Hz, the output waveforms had less than 20% difference than input
      waveforms. To reduce backflow of solutions into the pumps, the operational
      sequence of the valving program was modified, as well as differential etching of
      the valve seat depths. These modifications reduced backflow to the point that it
      was not detected. Gradients in glucose levels were applied in this work to
      stimulate single islets of Langerhans. Glucose gradients between 3 and 20 mM
      brought clear and intense oscillations of intracellular [Ca(2+)] indicating the
      system will be useful in future studies of cellular physiology.

PMID- 19178343
TI  - Effective saturation: a more informative metric for comparing peak separation in
      one- and two-dimensional separations.
AB  - A theoretical comparison is made of the numbers of observed peaks in one
      dimensional (1D) and two-dimensional (2D) separations having the same peak
      capacity, as calculated from the traditional metric of resolution. The
      shortcoming of the average minimum resolution of statistical overlap theory (SOT)
      for this comparison is described. A new metric called the "effective saturation"
      is introduced to ameliorate the shortcoming. Unlike the "saturation", which is
      the usual metric of peak crowding in SOT, the effective saturation is independent
      of the average minimum resolution and can be determined using traditional values
      of resolution and peak capacity. Our most important finding is that, under a wide
      range of practical conditions, 1D and 2D separations of the same mixture produce
      almost equal numbers of observed peaks when the traditional peak capacities of
      the separations are the same, provided that the effective saturation and not the
      usual saturation is used as the measure of crowding. This is the case when peak
      distributions are random and when edge effects are minor. The numerical results
      supporting this finding can be described by empirical functions of the effective
      saturation, including one for the traditional peak capacity needed to separate a
      given fraction of mixture constituents as observed peaks. The near equality of
      the number of observed peaks in 1D and 2D separations based on the effective
      saturation is confirmed by simulations. However, this equality is compromised in
      2D separations when edge effects are large. The new finding does not contradict
      previous predictions by SOT of differences between 1D and 2D separations at equal
      saturation. Indeed, the simulations reaffirm their validity. Rather, the usual
      metric, i.e., the saturation, is just not as simple a metric for comparing 1D and
      2D separations as is the new metric, i.e., the effective saturation. We strongly
      recommend use of the new metric for its great simplifying effect.

PMID- 19178344
TI  - Gas chromatographic separation of isotopic molecules using a cavitand-impregnated
      ionic liquid stationary phase.
AB  - Cavitands, which are a class of compounds with deep open-ended cavities, are
      known to exhibit remarkable molecular recognition ability through host-guest
      interactions because of their unique structures. It is known that isotopic
      molecules can be differentiated in the small spaces provided by completely closed
      capsules in solution. To determine if this subtle molecular recognition ability
      extends to cavitands, we have developed a new method to facilitate the use of
      cavitands as stationary phases (SPs) in gas chromatography (GC). These involve a
      "pseudo heterogeneous two-phase system"; specifically, ionic liquids (ILs) were
      used as solvents to coat three cavitands with slightly different structures onto
      GC columns. When cavitand-coated columns were compared with columns coated with
      only ILs, it was clear that cavitands not only extended the utilization but also
      substantially improved separation efficiency of the columns. It was found that
      cavitand-coated columns can effectively separate many different types of isotopic
      compounds including aromatic hydrocarbons (mixture of chlorobenzene-h(5) and
      chlorobenzene-d(5), mixture of 1,2-dichlorobenzene-h(4) and 1,2-dichlorobenzene
      d(4)), alcohols (methanol from its corresponding methanol-d, d(3), d(4)), ether,
      pyridine, and acetonitrile. The results also show that by modifying functional
      groups of the cavitand, from Et to C(11)H(23) or from amide to carboxylate, we
      can fully retain the molecular recognition ability of the cavitand. The drastic
      changes in the polarity of the SP from medium polar to nonpolar, or to polar,
      greatly extends the applicability of these cavitand-coated SPs. Compared to other
      GC SPs that are known to separate isotopic molecules, these cavitand-coated SPs
      can separate a relatively wider range of isotopic compounds at relatively lower
      temperature, with shorter column length and higher efficiency.

PMID- 19178345
TI  - Determination of NAD(+) and NADH in a single cell under hydrogen peroxide stress
      by capillary electrophoresis.
AB  - A capillary electrophoresis (CE) method based on an enzymatic cycling reaction is
      developed to determine both NAD(+) and NADH in a single cell in a single run. The
      detection limit can reach down to 0.2 amol of NAD(+) and 1 amol of NADH with a
      homemade capillary electrophoresis laser-induced fluorescence (CE-LIF) setup.
      This method shows good reproducibility and specificity. After an intact cell is
      injected into the capillary and lysed using a Tesla coil, intracellular NAD(+)
      and NADH were separated, incubated with the cycling buffer, and quantified by
      recording the amount of fluorescent product generated. Cellular NAD(+) and NADH
      levels of a rat myoblast cell line were determined using this method. Both NAD(+)
      and NADH levels decreased when the cells were exposed to oxidative stress induced
      by H(2)O(2). This may be due to the activation of the DNA repair enzyme, poly(ADP
      ribose) polymerase, in response to the oxidative damage imposed on DNA, since
      pretreatment of the cells with an inhibitor of these enzymes prevented the
      reduction of cellular NAD(+) and NADH levels.

PMID- 19178351
TI  - Complex thermal behavior of 11-cis-retinal, the ligand of the visual pigments.
AB  - Upon heating to 80 degrees C, 11-cis-retinal yields a mixture of all-trans
      retinal and 13-cis-retinal. This isomerization has been studied by means of
      density functional theory methods, and the computational results suggest a close
      competition between two mechanisms of very different nature. A classical internal
      rotation around the C11-C12 cis double bond, via a diradical transition state,
      accounts for the formation of the all-trans isomer. An intricate sequence of
      pericyclic reactions, namely a reversible [1,7]-H sigmatropic shift and a
      reversible 6-pi-oxa-electrocyclic reaction, is responsible for the formation of
      13-cis-retinal. Experiments using 11-cis-retinal labeled with deuterium at C19
      confirmed the mechanistic proposal and also revealed an unprecedented outcome on
      the product composition of isotopologues.

PMID- 19178352
TI  - Absolute reactivity of halo(pyridyl)carbenes.
AB  - A comprehensive series of halo(pyridyl)carbenes was generated by laser flash
      photolysis of the appropriate diazirines. Only the chloro- and bromo(2
      pyridyl)carbenes and the chloro- and bromo(3-pyridyl)carbenes could be directly
      observed, but the reactivity of all nine halo(pyridyl)carbenes could be directly
      studied using the standard and a modified pyridine-ylide approach. The carbenes
      were all ambiphilic, being highly reactive toward both electron-rich and election
      deficient alkenes. Second-order rate constants for these reactions ranged from
      2.9 x 10(6) to 3.5 x 10(9) M(-1) s(-1) and depended on both the position of the
      nitrogen atom within the pyridine ring and the nature of the halogen group, as
      well as the electrophilicity or nucleophilicity of the alkene. A reactivity trend
      with respect to the location of the nitrogen within the pyridine ring was
      observed, with the 4-pyridyl carbenes being the most reactive followed by the 2
      pyridylcarbenes and then the 3-pyridylcarbenes being the least reactive. This
      observed reactivity trend is consistent with the pyridyl ring acting as an
      overall electron-withdrawing group. The results also show that resonance
      delocalization of electron density into the nitrogen atom of the 4-pyridyl- and 2
      pyridylcarbenes in the transition state significantly reduces the effect of the
      adjacent halogen (F, Cl, or Br) on the reactivity of the pyridyl carbenes with a
      series of alkenes.

PMID- 19178353
TI  - Kinetic studies on nucleophilic substitution reactions of O-aryl thionobenzoates
      with azide, cyanide, and hydroxide: contrasting reactivity and mechanism.
AB  - A kinetic study is reported for nucleophilic substitution reactions of O-Y
      substituted phenyl thionobenzoates (1a-h) and O-4-nitrophenyl X-substituted
      thionobenzoates (2a-f) with N(3)(-) and CN(-) in 80 mol % H(2)O-20 mol % DMSO at
      25.0 +/- 0.1 degrees C. The Bronsted-type plot for the reactions of 1a-h with
      N(3)(-) exhibits a downward curvature, i.e., the slope (beta(lg)) changes from 
      1.10 to -0.33 as the leaving group basicity decreases, indicating that the
      reactions proceed through a stepwise mechanism with a change in rate-determining
      step (RDS). In contrast, the Bronsted-type plot for the corresponding reactions
      with CN(-) is linear with a beta(lg) value of -0.33. This value is similar to
      that found previously for the reactions of 1a-h with OH(-) (-0.35). Besides,
      sigma(o) constants result in much better Hammett correlation than sigma(-)
      constants. Thus, the reactions with CN(-) and OH(-) have been concluded to
      proceed through a stepwise mechanism in which departure of the leaving group
      occurs after RDS. Reactions of 2a-f with N(3)(-) and CN(-) result in nonlinear
      Hammett plots. However, the Yukawa-Tsuno plots for the same reactions exhibit
      excellent linearity with r = 0.5 +/- 0.1, indicating that the nonlinear Hammett
      plots are not due to a change in RDS but are caused by ground state stabilization
      through resonance interactions between the electron-donating substituent and the
      thio carbonyl functionality. Calculation of the k(1) values (nucleophile attack
      as RDS) for the reactions of 1a-h with N(3)(-) indicates that azide ion is more
      reactive than OH(-) toward the thione esters, although the former is over 11
      pK(a) units less basic than the latter. The high polarizability of N(3)(-) has
      been suggested to be responsible for its great affinity for the polarizable
      thione esters 1a-h and 2a-f.

PMID- 19178354
TI  - A revised conformational code for the exhaustive analysis of conformers with one
      to-one correspondence between conformation and code: application to the VCD
      analysis of (S)-ibuprofen.
AB  - A revised conformational code for the exhaustive analysis of conformers of all
      classes of molecules is proposed and applied to the vibrational circular
      dichroism (VCD) analysis of (S)-ibuprofen. The revised code can strictly define
      the conformation of compounds with relatively high-symmetry substituents and is
      especially useful for visualizing conformational changes in ligands and proteins.
      The conformational analysis of (S)-ibuprofen using the code in the solution state
      reveals that the four energetically preferred conformations, ibut-3alpha2alpha
      sigma(phpa-3alpha sigma2alpha), ibut-3alpha2alpha tau(phpa-3alpha tau2alpha),
      ibut-2beta3beta tau(phpa-3alpha tau2alpha), and ibut-2beta3beta sigma(phpa-3alpha
      sigma2alpha), exist in the monomer and dimer forms. In CDCl(3) solution, the
      dimer form is stabilized as the "U"-shape, and the ease of crystallization is
      largely ascribed to the conformation of phpa-3alpha2alpha for (S)-ibuprofen. The
      new version of the conformational code has the possibility to be used as a tool
      for the exhaustive analysis of conformers of all kinds of chemical compounds,
      conformome analysis, and in the future for metabolome, proteome, and genome
      analyses.

PMID- 19178356
TI  - Structure, stereodynamics and absolute configuration of the atropisomers of
      hindered arylanthraquinones.
AB  - Anthraquinone substituted by 2-methyl-1-naphthyl groups in positions 1,8 yields
      syn (meso) and anti (racemic) isomers (red and yellow colored, respectively) that
      interconvert with a barrier of 35.4 kcal mol(-1) in solution. Their structures
      were identified by NOE experiments in solution and X-ray diffraction in the
      solids. The racemic anti form (C(2) point group) entails two atropisomers that
      were separated by enantioselective HPLC: the absolute configuration was assigned
      by TD-DFT simulation of the ECD spectrum. Two atropisomers were also separated
      and assigned in the case of anthraquinone bearing a single 2-methyl-1-naphthyl
      substituent in position 1.

PMID- 19178355
TI  - Quinoxalines XV. Convenient synthesis and structural study of pyrazolo[1,5
      a]quinoxalines.
AB  - A series of aryloxymethylquinoxaline oximes, hitherto unknown and synthesized
      from the corresponding aldehydes, afforded in only one step pyrazolo[1,5
      a]quinoxalines in the presence of acetic anhydride at high temperatures. A formal
      [3,5]-sigmatropic rearrangement was proposed as the mechanistic rationale for
      this unprecedented transformation. Saponification with potassium hydroxide
      furnished the free phenol derivatives which were studied by NMR spectroscopy and
      accompanying theoretical DFT calculations, establishing intramolecular hydrogen
      bonding and the spatial magnetic properties. Additionally, mass spectrometric
      fragmentation was investigated by B/E-linked scans and collision-induced
      dissociation experiments. The fragmentation pattern devoted a new gas phase
      rearrangement process, which proved to be unique and characteristic for
      pyrazolo[1,5-a]quinoxalines.

PMID- 19178357
TI  - A preparatively convenient ligand-free catalytic PEG 2000 Suzuki-Miyaura
      coupling.
AB  - A ligand-free Suzuki-Miyaura reaction for the cross-coupling of aryl and
      heteroaryl bromides with aryl and heteroarylboronic acids has been developed
      utilizing catalytic polyethylene glycol 2000 (PEG 2000). This preparatively
      convenient system afforded the corresponding cross-coupled products in good to
      excellent isolated yields after a simple aqueous workup. Transmission electron
      microscopy (TEM) analysis of the Pd-PEG 2000 catalyst system revealed in situ
      generated palladium nanoparticles after only 1 min of reaction.

PMID- 19178358
TI  - Synthesis of alpha-chloroaldoxime O-methanesulfonates and their use in the
      synthesis of functionalized benzimidazoles.
AB  - Three different alpha-chloroaldoxime O-methanesulfonates were synthesized to
      investigate their chemical properties. The compounds were found to be stable and
      were able to be stored at ambient temperature without any precautions. The
      reactions with anilines were investigated, and it was found that an additive is
      required to activate the sulfonate. TMEDA was found to be the most efficient
      additive, and various benzimidazoles were synthesized through the reaction.

PMID- 19178359
TI  - Facile stereoselective synthesis of fluorinated flavanone derivatives via a one
      pot tandem reaction.
AB  - A series of fluorinated flavanones were synthesized in moderate to good yields
      with excellent diastereoselectivities under mild reaction conditions via a one
      pot tandem procedure involving a proline-catalyzed Knoevenagel condensation, a
      Michael addition, and an electrophilic fluorination by NFSI.

PMID- 19178385
TI  - Endurance exercise improves walking distance in MS patients with fatigue.
AB  - OBJECTIVES: Effects of endurance training in multiple sclerosis (MS) patients
      complaining of motor fatigue. MATERIALS AND METHODS: Thirty MS patients
      complaining of fatigue with low to moderate disabilities randomly allocated to
      the intervention (thrice weekly 45-min intervals of endurance exercise) or
      control treatment (three 45-min episodes of stretching, balance training and
      coordination), both as 'add-on' therapy for 3 weeks during inpatient
      rehabilitation. RESULTS: Maximal walking distance before intervention averaged
      1043 +/- 568 and 1163 +/- 750 m in the two groups. The intervention group
      increased its maximal walking distance by 650 +/- 474 m. The control group
      extended its walking distance by 96 +/- 70 m. CONCLUSIONS: The present data
      confirm a strong effect of endurance exercise on maximal walking distance.
      Remarkably, there were no parallel improvements on the Modified Fatigue Impact
      Scale, the Beck Depression Inventory and the Hamburg Quality of Life
      Questionnaire for MS.

PMID- 19178384
TI  - Structure of human insulin-like peptide 5 and characterization of conserved
      hydrogen bonds and electrostatic interactions within the relaxin framework.
AB  - INSL5 (insulin-like peptide 5) is a two-chain peptide hormone related to insulin
      and relaxin. It was recently discovered through searches of expressed sequence
      tag databases and, although the full biological significance of INSL5 is still
      being elucidated, high expression in peripheral tissues such as the colon, as
      well as in the brain and hypothalamus, suggests roles in gut contractility and
      neuroendocrine signalling. INSL5 activates the relaxin family peptide receptor 4
      with high potency and appears to be the endogenous ligand for this receptor, on
      the basis of overlapping expression profiles and their apparent co-evolution. In
      the present study, we have used solution-state NMR to characterize the three
      dimensional structure of synthetic human INSL5. The structure reveals an
      insulin/relaxin-like fold with three helical segments that are braced by three
      disulfide bonds and enclose a hydrophobic core. Furthermore, we characterized in
      detail the hydrogen-bond network and electrostatic interactions between charged
      groups in INSL5 by NMR-monitored temperature and pH titrations and undertook a
      comprehensive structural comparison with other members of the relaxin family,
      thus identifying the conserved structural features of the relaxin fold. The B
      chain helix, which is the primary receptor-binding site of the relaxins, is
      longer in INSL5 than in its close relative relaxin-3. As this feature results in
      a different positioning of the receptor-activation domain Arg(B23) and Trp(B24),
      it may be an important contributor to the difference in biological activity
      observed for these two peptides. Overall, the structural studies provide
      mechanistic insights into the receptor selectivity of this important family of
      hormones.

PMID- 19178386
TI  - Smell and taste disorders in polyneuropathy: a prospective study of chemosensory
      disorders.
AB  - OBJECTIVE: The aim of the study was to assess the occurrence and the frequency of
      chemosensory dysfunction in patients with polyneuropathy (PNP). METHODS: We
      performed a prospective observational study. Olfactory function was assessed
      using the standardized 'Sniffin' Sticks' test to measure odor threshold for
      phenyl ethyl alcohol, odor discrimination, and odor identification. Gustatory
      function was assessed using the standardized 'taste strips' test. In addition, we
      assessed etiology, neurophysiology, and severity of the PNP, and the patients'
      comorbidities and medication. RESULTS: A total of 53 consecutive patients were
      enrolled (15 women, 38 men; mean age 61 years); 27 of them (51%) exhibited
      olfactory dysfunction and 23 of them (43%) gustatory dysfunction. Patients with
      diabetic PNP had significantly lower taste scores than patients with
      inflammatory, genetic, or idiopathic PNP. In addition, odor identification was
      negatively correlated with PNP severity. CONCLUSION: The applied bedside tests
      are useful to detect chemosensory dysfunction in patients with PNP. Chemosensory
      dysfunction is quite frequent in these patients.

PMID- 19178387
TI  - A comparative study of cardiac dysautonomia in autosomal dominant spinocerebellar
      ataxias and idiopathic sporadic ataxias.
AB  - OBJECTIVES: Comparative evaluation of cardiac dysautonomia in spinocerebellar
      ataxias (SCA) and idiopathic sporadic ataxias (IA) not fulfilling the criteria of
      multiple system atrophy. MATERIAL AND METHODS: Cardiac autonomic functions were
      evaluated in 14 SCA (SCA1 = 6, SCA2 = 5 and SCA3 = 3) and 10 IA patients,
      comparable for age, age at onset, duration and severity of illness. The results
      were categorized as early, definitive, or severe autonomic involvement (EI, DI
      and SI respectively) based on the degree of abnormalities on tests of
      parasympathetic and sympathetic pathways. RESULTS: Cardiac autonomic dysfunction
      was present in all (EI = 25.0%, DI = 41.7% and SI = 33.3%), parasympathetic
      dysfunction being an early feature. SI was most often present in SCA3 (100%),
      followed by those with SCA1 (66.7%), and SCA2 (20%) and none in IA. CONCLUSIONS:
      Cardiac dysautonomia was common in both SCA and IA, although the severity was
      greater in SCA. Among SCAs, the severity was greatest in SCA3, followed by SCA2
      and least in SCA1.

PMID- 19178388
TI  - Immediate sequential cataract surgery: the pros and cons of a controversial
      approach.

PMID- 19178389
TI  - Is it possible to detect the presence of adenovirus in conjunctiva before the
      onset of conjunctivitis?
AB  - PURPOSE: It is widely accepted that patients with adenoviral conjunctivitis are
      contagious approximately as long as 14 days after the onset. However, there is
      controversy about whether patients with adenoviral conjunctivitis are contagious
      during the incubation period. We investigated the potential of the eye as a
      source for spreading infection during the incubation period by analysing the
      presence of adenovirus (Ad) in contralateral eyes before onset in patients with
      bilateral adenoviral conjunctivitis using the immunochromatography (IC) test and
      polymerase chain reaction (PCR). METHODS: Patients with adenoviral conjunctivitis
      were directed to visit an outpatient clinic at approximately 3-day intervals
      until onset in the contralateral eye or 2 weeks after onset in the first eye.
      Conjunctival scrapings obtained from the first infected eye and the contralateral
      eye before and after onset were tested to detect Ad antigen using the IC test and
      PCR. RESULTS: Out of the 32 cases, 23 (72%) developed conjunctivitis in the
      contralateral eye. Among these bilateral cases, 18 (78%) were found positive for
      Ad by PCR after onset in the contralateral eye. However, no specimen obtained
      before onset showed a positive result for Ad in both tests. CONCLUSION: Although
      there is a possibility that eyes are contagious during the incubation period of
      adenoviral conjunctivitis in some situations, these results suggest that the
      possibility of the eye acting as a source for spreading infection during the
      incubation period is very small.

PMID- 19178390
TI  - Intraocular pressure control over 24 hours using travoprost and timolol fixed
      combination administered in the morning or evening in primary open-angle and
      exfoliative glaucoma.
AB  - PURPOSE: To evaluate intraocular pressure (IOP) control over 24 hours using
      travoprost and timolol fixed combination (TTFC) administered in the morning or
      evening in primary open-angle and exfoliative glaucoma. METHODS: Patients were
      randomized to TTFC administered in either the morning or evening for 8 weeks.
      Previously treated patients underwent an untreated washout period of 4-6 weeks,
      after which baseline IOP was required to be > 25 mm Hg and < 38 mmHg (in two
      readings taken at 10.00 +/- 1 hours). During the treatment period, IOP was
      measured at 10.00, 14.00, 18.00, 22.00, 02.00 and 06.00 hours. Patients were then
      treated with the opposite dosing regimen for 8 weeks and IOP measurements were
      repeated. RESULTS: In 32 subjects who completed the study, the untreated baseline
      IOP following washout was 27.7 +/- 3.5 mmHg. Both dosing regimens reduced IOP
      from baseline at each time-point and throughout the 24-hour diurnal curve (p <
      0.0001). When treatments were compared directly, evening dosing (18.4 +/- 3.3
      mmHg) provided a statistically significant lower 24-hour curve than morning
      dosing (19.2 +/- 3.5 mmHg; p = 0.001). Evening dosing also resulted in a lower 24
      hour IOP fluctuation (3.8 +/- 1.6 mmHg) than morning dosing (5.1 +/- 1.6 mmHg; p
      = 0.0002) and lower peak IOP (p = 0.0003). CONCLUSIONS: Both morning and evening
      administration of TTFC provide effective 24-hour IOP reduction, but evening
      dosing demonstrates better 24-hour pressure control.

PMID- 19178391
TI  - Intravitreal bevacizumab for choroidal neovascularization secondary to choroidal
      osteoma.

PMID- 19178392
TI  - Ophthalmic lymphoma: epidemiology and pathogenesis.
AB  - With a lifetime risk of 1% and 700 new cases per year, Non-Hodgkin lymphoma (NHL)
      is the seventh most frequent type of cancer in Denmark. The incidence of NHL has
      increased considerably in Western countries over the last decades; consequently,
      NHL is an increasing clinical problem. Ophthalmic lymphoma, (lymphoma localized
      in the ocular region, i.e. eyelid, conjunctiva, lacrimal sac, lacrimal gland,
      orbit, or intraocularly) is relatively uncommon, accounting for 5%-10% of all
      extranodal lymphomas. It is, however, the most common orbital malignancy. The
      purpose of this thesis was to review specimens from all Danish patients with a
      diagnosis of ophthalmic lymphoma during the period 1980-2005, in order to
      determine the distribution of lymphoma subtypes, and the incidence- and time
      trends in incidence for ophthalmic lymphoma. Furthermore, an extended analysis of
      the most frequent subtype, extranodal marginal zone lymphoma (MALT lymphoma), was
      done to analyse clinical factors and cytogenetic changes with influence on
      prognosis. A total of 228 Danish patients with a biopsy-reviewed verified
      diagnosis of ocular adnexal-, orbital-, or intraocular lymphoma were identified.
      We found that more than 50% of orbital- and ocular adnexal lymphomas were of the
      MALT lymphoma subtype, whereas diffuse large B-cell lymphoma (DLBCL) predominated
      intraocularly (Sjo et al. 2008a). Furthermore, lymphoma arising in the lacrimal
      sac was surprisingly predominantly DLBCL (Sjo et al. 2006). Incidence rates were
      highly dependent on patient age. There was an increase in incidence rates for the
      whole population from 1980 to 2005, corresponding to an annual average increase
      of 3.4% (Sjo et al. 2008a). MALT lymphoma arising in the ocular region was found
      in 116 patients (Sjo et al. 2008b). One third of patients had a relapse or
      progression of disease after initial therapy and relapses were frequently found
      at extra-ocular sites. Overall survival, however, was not significantly poorer
      for patients with relapse. Furthermore, we found that the frequency of
      translocations involving the MALT1- and IGH-gene loci is low in ocular region
      MALT lymphoma (2 of 42, 5%), but may predict increased risk of relapse (Sjo et
      al. 2008b). In conclusion the incidence of ophthalmic lymphoma is increasing at a
      high rate in Denmark. Ophthalmic lymphoma consists primarily of MALT lymphoma.
      The molecular pathogenesis of MALT lymphoma arising in the ocular region rarely
      involves translocations in the MALT1- and IGH-gene loci.

PMID- 19178393
TI  - Ecological studies and the big puzzle of falling suicide rates.

PMID- 19178395
TI  - Violence among schizophrenia out-patients compliant with medication: prevalence
      and associated factors.
AB  - OBJECTIVE: Aggressive behaviour has been related to schizophrenia both in in
      patient and out-patient samples. In this study, we aimed to assess the prevalence
      and factors associated with aggressive behaviour in out-patient compliant with
      their prescribed medication. METHOD: Eight hundred and ninety-five patients were
      interviewed at Community-Based Mental Health Services about aggressive-violent
      behaviour within the week prior to the study visit. Adult patients diagnosed with
      schizophrenia and receiving stable pharmacological treatment were enrolled.
      Presence of aggressive episodes, including type of aggression, severity and
      frequency, was assessed with the Modified Overt Aggression Scale (MOAS). Violence
      was defined as a score of 3 or more in any of the MOAS subscores. RESULTS:
      Prevalence of recent aggressive behaviour was 5.07%, (95% CI 5.04-5.10), where
      47% (43 behaviours 91) reached the violent threshold. Among the 91 violent
      episodes rated, most episodes were verbal (44%), followed by physical violence
      towards objects (29%), violence towards others (19%) and self-directed violence
      (8%). Recent episodes of any severity were more likely among patients with a
      history of violence and also with relapses within the previous year and with low
      treatment satisfaction. CONCLUSION: Five per cent of the studied cases showed
      aggressive behaviour in the week prior to assessment, despite having been
      compliant with their medication. Most aggressive behaviour was verbal rather than
      physical.

PMID- 19178394
TI  - Which comes first: atypical antipsychotic treatment or cardiometabolic risk?
AB  - OBJECTIVE: To provide an overview for practicing clinicians on the
      pharmacological basis of cardiometabolic risk induced by antipsychotic drugs in
      patients with serious mental illness, to propose hypotheses to explain these
      risks and to give tips for managing cardiometabolic risk during antipsychotic
      treatment. METHOD: A MEDLINE search using terms for atypical antipsychotics
      (including individual drug names), metabolic, cardiovascular, weight gain and
      insulin resistance, cross-referenced with schizophrenia was performed on articles
      published between 1990 and May 2008. RESULTS: Strong evidence exists for
      significant cardiometabolic risk differences among several antipsychotic agents.
      Histamine H1 and serotonin 5HT2C antagonism are associated with risk of weight
      gain, but receptor targets for dyslipidemia and insulin resistance have not yet
      been identified. Convincing data indicate that hypertriglyceridemia and insulin
      resistance may occur in the absence of weight gain with certain antipsychotics.
      CONCLUSION: Although lifestyle and genetics may contribute independent risks of
      cardiometabolic dysfunction in schizophrenia and other serious mental illness,
      antipsychotic treatment also represents an important contributor to risk of
      cardiometabolic dysfunction, particularly for certain drugs and for vulnerable
      patients. Mental health professionals must learn to recognize the clinical
      signposts indicating antipsychotic-related cardiometabolic problems to forestall
      progression to type II diabetes, cardiovascular events and premature death.

PMID- 19178397
TI  - Drug allergy and hypersensitivity: still a hot topic.

PMID- 19178399
TI  - Adrenaline for the treatment of anaphylaxis: cochrane systematic review.
AB  - BACKGROUND: Anaphylaxis is a serious allergic reaction that is rapid in onset and
      may cause death. Adrenaline is recommended as the initial treatment of choice for
      anaphylaxis. OBJECTIVES: To assess the benefits and harms of adrenaline in the
      treatment of anaphylaxis. METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1966
      to March 2007), EMBASE (1966 to March 2007), CINAHL (1982 to March 2007), BIOSIS
      (to March 2007), ISI Web of Knowledge (to March 2007) and LILACS (to March 2007).
      We also searched websites listing ongoing trials: http://www.clinicaltrials.gov/,
      http://www.controlledtrials.com and http://www.actr.org.au/ and contacted
      pharmaceutical companies and international experts in anaphylaxis in an attempt
      to locate unpublished material. Randomized and quasi-randomized controlled trials
      comparing adrenaline with no intervention, placebo or other adrenergic agonists
      were eligible for inclusion. Two authors independently assessed articles for
      inclusion. RESULTS: We found no studies that satisfied the inclusion criteria.
      CONCLUSIONS: On the basis of this review, we are unable to make any new
      recommendations on the use of adrenaline for the treatment of anaphylaxis. In the
      absence of appropriate trials, we recommend, albeit on the basis of less than
      optimal evidence, that adrenaline administration by intramuscular injection
      should still be regarded as first-line treatment for the management of
      anaphylaxis.

PMID- 19178398
TI  - Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD
      database and the GALEN platform. The Galenda project.
AB  - Nonallergic hypersensitivity and allergic reactions are part of the many
      different types of adverse drug reactions (ADRs). Databases exist for the
      collection of ADRs. Spontaneous reporting makes up the core data-generating
      system of pharmacovigilance, but there is a large under-estimation of
      allergy/hypersensitivity drug reactions. A specific database is therefore
      required for drug allergy and hypersensitivity using standard operating
      procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult
      and current pharmacovigilance algorithms are insufficient. Although difficult,
      the diagnosis of drug allergy/hypersensitivity has been standardized by the
      European Network for Drug Allergy (ENDA) under the aegis of the European Academy
      of Allergology and Clinical Immunology and SOPs have been published. Based on
      ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework
      Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has
      been established under FileMaker((R)) Pro 9. It is already available online in
      many different languages and can be accessed using a personal login. GA(2)LEN is
      a European network of 27 partners (16 countries) and 59 collaborating centres (26
      countries), which can coordinate and implement the DAHD across Europe. The
      GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears
      to be of great interest for the reporting of allergy/hypersensitivity ADRs in
      conjunction with other pharmacovigilance instruments.

PMID- 19178400
TI  - Histamine N-methyltransferase 939A>G polymorphism affects mRNA stability in
      patients with acetylsalicylic acid-intolerant chronic urticaria.
AB  - BACKGROUND: Histamine plays an important role in allergic inflammation. Histamine
      levels are regulated by histamine N-methyltransferase (HNMT). OBJECTIVE: To
      investigate the functional variability of HNMT gene in relation to genetic
      polymorphisms in patients with aspirin intolerant chronic urticaria (AICU).
      METHODS: Two single-nucleotide polymorphisms of the HNMT gene (314C>T, 939A>G)
      were genotyped in chronic urticaria patients. The functional variability of 3'
      untranslated region polymorphism (3'-UTR) was assessed using the pEGFP-HNMT 3'
      UTR reporter construct to examine mRNA stability and fluorescence-tagged protein
      expression. The HNMT enzymatic activities related to the 939A>G polymorphism were
      examined both in the human mast cells (HMC-1) transfected with the pHNMT CDS-3'
      UTR construct and in the patients' red blood cells (RBCs). Histamine release from
      the basophils of AICU patients was examined. RESULTS: The 939A>G polymorphism was
      significantly associated with the AICU phenotype, while no association was found
      with the 314C>T polymorphism. An in vitro functional study using HMC-1 cells
      demonstrated that the 939A allele gave lower levels of HNMT mRNA stability, HNMT
      protein expression, and HNMT enzymatic activity and higher histamine release than
      the 939G allele. The in vivo functional study demonstrated that the AICU patients
      with the 939A allele had lower HNMT activity in RBC lysates and higher histamine
      release from their basophils. CONCLUSION: The HNMT 939A>G polymorphism lowers
      HNMT enzymatic activity by decreasing HNMT mRNA stability, which leads to an
      increase in the histamine level and contributes to the development of AICU.

PMID- 19178401
TI  - Contact allergies in haemodialysis patients: a prospective study of 75 patients.
AB  - BACKGROUND: Haemodialysis exposes patients to many potentially sensitizing
      allergens. OBJECTIVES: The primary objective of this study was to evaluate the
      prevalence of delayed hypersensitivity in a population of haemodialysis patients.
      Secondary objectives were to identify the possible risk factors for contact
      sensitization and to propose a series of skin tests adapted to haemodialysis
      patients. METHODS: A prospective monocentric study was carried out in a
      nonselected population of haemodialysis patients. For each patient, medical
      history of atopy and allergic contact dermatitis, ongoing treatments (including
      topical ones), presence of eczema at the site of vascular access for
      haemodialysis were recorded. Allergological investigation included delayed
      hypersensitivity tests (European Environmental and Contact Dermatitis Research
      Group battery, tests GERDA, additional list and a battery of antiseptics and
      other dialysis-specific allergens) and latex skin prick test. RESULTS: Seventy
      five patients (41 men, 34 women, mean age of 65 years old), with a mean 3.8 years
      under dialysis, were included. Nineteen patients (25%) had at least one positive
      skin test and 13 (17%) a positive patch test to at least one allergen relative to
      dialysis process including eight tests to lidocaine-prilocaine cream and three to
      povidone-iodine. Tests results seemed clinically relevant since nine patients had
      localized pruritus at the fistula site and six patients active eczema around it.
      CONCLUSION: Contact sensitizations are frequent in haemodialysis patients and are
      linked to vascular access conditioning especially the use of lidocaine-prilocaine
      cream. Designing a specific test battery could help to diagnose the potential
      allergens and subsequently to give advice to avoid contact with sensitizing
      agents.

PMID- 19178402
TI  - Skin testing and drug provocation in the diagnosis of nonimmediate reactions to
      aminopenicillins in children.
AB  - BACKGROUND: Nonimmediate allergic reactions (NIR) to aminopenicillin include
      several entities, the most common of which are urticaria-like and maculopapular
      exanthemas. AIMS OF THE STUDY: To evaluate a group of children who developed one
      or more episodes of skin reactions suggestive of NIR after aminopenicillin
      administration. METHODS: The inclusion criteria required negative immediate skin
      tests and absence of specific IgE antibodies to different penicillins.
      Intradermal and patch tests were carried out with delayed readings and, if
      negative, a drug-provocation test including a full therapeutic course of the drug
      was given. Two different groups were compared: A) children with positive skin
      testing or a positive drug-provocation test and B) children with negative skin
      testing and good tolerance after a drug-provocation test. RESULTS: Group A was
      composed of 20 patients. Positive intradermal/patch tests were found in one
      patient and in the remaining 19, a positive response to a drug-provocation test
      confirmed the diagnosis. Group B (the control group) consisted of 19 patients
      with similar symptoms after aminopenicillin intake but good tolerance. No
      differences in age, dose or number of previous treatments were observed between
      the groups. The clinical entities were also similar in both groups. CONCLUSIONS:
      Reproducible nonimmediate skin reactions to aminopenicillins may occur in
      children in spite of negative skin testing. The value of this diagnostic
      procedure seems to be limited in this type of reaction, with drug-provocation
      tests (DPT) being a reasonable and safe alternative if the diagnosis has to be
      confirmed.

PMID- 19178403
TI  - Skin testing in patients with hypersensitivity reactions to iodinated contrast
      media - a European multicenter study.
AB  - BACKGROUND: Iodinated contrast media cause both immediate and nonimmediate
      hypersensitivity reactions. The aim of this prospective study was to determine
      the specificity and sensitivity of skin tests in patients who have experienced
      such reactions. METHODS: Skin prick, intradermal and patch tests with a series of
      contrast media were conducted in 220 patients with either immediate or
      nonimmediate reaction. Positive skin tests were defined according to
      internationally accepted guidelines. Seventy-one never-exposed subjects and 11
      subjects who had tolerated contrast medium exposure, served as negative controls.
      RESULTS: Skin test specificity was 96-100%. For tests conducted within the time
      period from 2 to 6 months after the reaction, up to 50% of immediate reactors and
      up to 47% of nonimmediate reactors were skin test positive. For immediate
      reactors, the intradermal tests were the most sensitive, whereas delayed
      intradermal tests in combination with patch tests were needed for optimal
      sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more
      common in the nonimmediate than in the immediate group. Interestingly, 49% of
      immediate and 52% of nonimmediate symptoms occurred in previously unexposed
      patients. Many of these patients were skin test positive, indicating that they
      were already sensitized at the time of first contrast medium exposure.
      CONCLUSIONS: These data suggest that at least 50% of hypersensitivity reactions
      to contrast media are caused by an immunological mechanism. Skin testing appears
      to be a useful tool for diagnosis of contrast medium allergy and may play an
      important role in selection of a safe product in previous reactors.

PMID- 19178404
TI  - Negativization rates of IgE radioimmunoassay and basophil activation test in
      immediate reactions to penicillins.
AB  - BACKGROUND: Skin test sensitivity in patients with immediate allergy to
      penicillins tends to decrease over time, but no information is available
      concerning in vitro tests. We analysed the negativization rates of two in vitro
      methods that determine specific immunoglobulin E (IgE) antibodies, the basophil
      activation test using flow cytometry (BAT) and the radioallergosorbent test
      (RAST), in immediate allergic reactions to penicillins. METHODS: Forty-one
      patients with immediate allergic reactions to amoxicillin were followed up over a
      4-year period. BAT and RAST were performed at 6-month intervals. Patients were
      randomized into groups: Group I, skin tests carried out at regular intervals;
      Group II, skin tests made only at the beginning of the study. RESULTS:
      Differences were observed between RAST and BAT (P < 0.01), the latter showing
      earlier negativization. Considering different haptens, significant differences
      for the rate of negativization were only found for amoxicillin (P < 0.05).
      Comparisons between Groups I (n = 10) and II (n = 31) showed a tendency to become
      negative later in Group I with RAST. CONCLUSIONS: Levels of specific IgE
      antibodies tended to decrease over time in patients with immediate allergic
      reactions to amoxicillin. Conversion to negative took longer for the RAST assay,
      although the differences were only detected with the amoxicillin hapten. Skin
      testing influenced the rate of negativization of the RAST assay, contributing to
      maintenance of in vitro sensitivity. Because of the loss of sensitivity over
      time, the determination of specific IgE antibodies to penicillins in patients
      with immediate allergic reactions must be done as soon as possible after the
      reaction.

PMID- 19178405
TI  - Dietary exclusions for improving established atopic eczema in adults and
      children: systematic review.
AB  - Atopic eczema is the most common inflammatory skin disease of childhood in
      developed countries. We performed a systematic review of randomized controlled
      trials to assess the effects of dietary exclusions for the treatment of
      established atopic eczema. Nine trials (421 participants) were included, most of
      which were poorly reported. Six were studies of egg and milk exclusion (n = 288),
      one was a study of few foods (n = 85) and two were studies of an elemental diet
      (n = 48). There appears to be no benefit of an egg- and milk-free diet in
      unselected participants with atopic eczema. There is also no evidence of benefit
      in the use of an elemental or few-foods diet in unselected cases of atopic
      eczema. There may be some benefit in using an egg-free diet in infants with
      suspected egg allergy who have positive specific IgE to eggs - one study found
      51% of the children had a significant improvement in body surface area with the
      exclusion diet as compared with normal diet (95% CI 1.07-2.11) and change in
      surface area and severity score was significantly improved in the exclusion diet
      as compared with the normal diet at the end of 6 weeks (MD 5.50, 95% CI 0.19
      10.81) and end of treatment (MD 6.10, 95% CI 0.06-12.14). Despite their frequent
      use, we find little good quality evidence to support the use of exclusion diets
      in atopic eczema.

PMID- 19178406
TI  - New insights into the mechanism and management of allergic diseases: atopic
      dermatitis.
AB  - Rapidly increasing knowledge on the complex background of atopic dermatitis (AD)
      on the genetic, immunological and environmental level in combination with the
      continuous improvement in our diagnostic options has initiated an ongoing
      discussion on factors, which primarily promote the disease on one hand and
      mechanisms which emerge rather secondarily as a consequence of disease-specific
      modifications, on the other hand. Beside a sustained search for reliable and
      meaningful diagnostic tools for elicitors of the disease, novel therapeutic
      approaches are required, as most of the treatments of AD are limited to
      symptomatic therapies. In contrast, therapeutic approaches selectively regulating
      aberrant pathophysiological mechanisms in AD itself would be much more effective
      and promising.

PMID- 19178407
TI  - Missense mutation Thr309Lys in the coagulation factor XII gene in a Spanish
      family with hereditary angioedema type III.
AB  - BACKGROUND: A new type of hereditary angioedema (type III) affecting mainly women
      with normal C1-inhibitor level and function has been described. Exposition to
      estrogens is an important precipitating factor. Recently, a missense mutation in
      the gene of the blood coagulation factor XII (Hageman factor) has been reported
      in a few families with this type of hereditary angioedema. AIM: To study a
      patient and her family with recurrent swelling attacks during pregnancy. METHODS:
      Complement factors C3 and C4 as well as C1-inhibitor level and function were
      determined. Genomic DNA was isolated from venous blood samples and screened for
      mutations in the coagulation factor XII gene. RESULTS: C3 and C4 levels as well
      as C1-inhibitor level and function were normal. A missense mutation Thr309Lys was
      identified in factor XII gene with a heterozygotic pattern. This mutation was
      also identified in the mother of the patient, her daughter and her son.
      CONCLUSION: These results support that the mentioned mutation in factor XII gene
      causes hereditary angioedema type III.

PMID- 19178408
TI  - Interleukin-13 promoter gene polymorphism -1112C/T is associated with the
      systemic form of mastocytosis.
AB  - BACKGROUND: Mastocytosis is a heterogenous disease involving mast cells (MC) and
      their progenitors. Cutaneous and systemic variants of the disease have been
      reported. In contrast to cutaneous mastocytosis (CM), patients with systemic
      mastocytosis (SM) are at risk to develop disease progression or a nonMC-lineage
      haematopoietic neoplasm. Little is known, however, about factors predisposing for
      the development of SM. One factor may be cytokine regulation of MC progenitors.
      METHODS: We examined the role of the interleukin-13 (IL-13) promoter gene
      polymorphism -1112C/T, known to be associated with increased transcription, in
      mastocytosis using allele-specific polymerase chain reaction method. Serum
      tryptase and IL-13 levels were determined by immunoassay, and expression of the
      IL-13 receptor in neoplastic MC by reverse transcription-polymerase chain
      reaction and flow cytometry. RESULTS: The frequency of the -1112T allele of the
      IL-13 promoter was significantly higher in patients with SM compared with CM (P <
      0.008) and in mastocytosis patients compared with healthy controls (P < 0.0001).
      Correspondingly, the polymorphism was found to correlate with an elevated serum
      tryptase level (P = 0.004) and with adult-onset of the disease (P < 0.0015), both
      of which are almost invariably associated with SM. Serum IL-13 levels were also
      higher in SM patients compared with CM (P = 0.011), and higher in CT- than in CC
      carriers (P < 0.05). Finally, we were able to show that neoplastic human MC
      display IL-13 receptors and grow better in IL-13-containing medium. CONCLUSIONS:
      The -1112C/T IL-13 gene polymorphism and the resulting 'hypertranscription' may
      predispose for the development of SM.

PMID- 19178409
TI  - Atopic dermatitis and allergic reactions to individual fragrance chemicals.
AB  - BACKGROUND: Allergic contact dermatitis prevalence is reported as equal in atopic
      and nonatopic dermatitis. Atopic dermatitis is under-represented in those with
      allergic contact dermatitis to agents having cutaneous and dietary exposure. We
      compared rates of atopic dermatitis between patients with allergic contact
      dermatitis arising out of individual fragrance chemicals with known
      oral/cutaneous exposure against exclusively cutaneous exposure. METHODS: Between
      1982 and 2007, 37 065 dermatitis patients were tested with Fragrance mix I. Those
      who were positive were tested for individual fragrance allergy. Chemicals were
      categorized according to whether their exposure pattern was solely cutaneous,
      oral or mixed. Current and past atopic dermatitis rates were compared between the
      whole population and groups allergic to individual fragrances. Age and gender
      were controlled. RESULTS: Cinnamic alcohol and cinnamal allergy groups had
      reduced rates of both 'current' [24/266 (9.0%) P = 0.0008, 38/364 (10.4%) P =
      0.0005] and 'past' atopic dermatitis [44/266 (16.5%) P = 0.009, 70/346 (19.2%) P
      = 0.037]. Atopic dermatitis rates in groups allergic to Evernia prunastri and
      hydroxycitronellal (cutaneous exposure only) were not reduced [120/597 (20.1%)
      and 41/153 (26.8%)]. Groups allergic to cinnamic alcohol (P < 0.0001, P < 0.0001)
      and cinnamal (P < 0.0001, P < 0.004) had reductions in 'current' and 'past'
      atopic dermatitis, compared with Evernia prunastri. CONCLUSIONS: Patients
      allergic to individual fragrances with dietary exposure have reduced rates of
      atopic dermatitis. This suggests that patients with atopic dermatitis have
      heightened oral tolerance to dietary haptens, in contrast to the known close
      association of atopic dermatitis with food-protein allergy. Haptens may interfere
      with food protein tolerance by binding to soluble protein to alter its
      configuration and immunogenic profile.

PMID- 19178410
TI  - Relevance of (IgG anti-IgE)-IgE complexes, IgG subclass and modern IgG antibody
      autoanalyzers in the dying IgG reagin story.

PMID- 19178411
TI  - Is it time to cut down on steroids?

PMID- 19178412
TI  - Potential role of NKG2D and its ligands in organ transplantation: new target for
      immunointervention.
AB  - NKG2D is one of the best characterized activating receptors on Natural Killer
      (NK) and CD8+ T cells. This receptor recognizes several different ligands
      (MICA/MICB and ULBPs) induced by cellular stress and infection. In addition to
      the role described in cancer surveillance, recent data highlight the importance
      of NKG2D and its ligands in organ transplantation. Allografts show evidence of
      MICA and MICB expression in both acute and chronic rejection. The presence of
      anti-MICA antibodies has been correlated with incidence of graft rejection.
      Furthermore, NKG2D-ligand engagement activates NK cells, which provides T-cell
      costimulation, and enhances antigen specific CTL-mediated cytotoxicity. Activated
      NK cells may function as a bridge between innate and adaptive immunity associated
      with transplantation. Activated NK cells in response to IL-15 can also trigger
      organ rejection through NKG2D and affect the maturation of both donor and
      recipient antigen presenting cells (APCs) and ultimately the T-cell allogeneic
      response. Regulatory T cells, which modulate T-cell responses in organ
      transplantation and infections, were reduced in numbers by NK cells exposed to
      intracellular pathogens, possibly via interaction with one NK2GD receptor.
      Blockage of NKG2D-NKG2D-L interactions provides a novel pathway for development
      of inhibitors. These studies have important clinical and therapeutic implications
      in solid organ transplantation.

PMID- 19178413
TI  - Interlaboratory comparison of cytomegalovirus viral load assays.
AB  - To assess interlaboratory variability in qualitative and quantitative
      cytomegalovirus (CMV) viral load (VL) testing, we distributed a panel of samples
      to 33 laboratories in the USA, Canada and Europe who performed testing using
      commercial reagents (n = 17) or laboratory-developed assays (n = 18). The panel
      included two negatives, seven samples constructed from purified CMV nucleocapsids
      in plasma (2.0-6.0 log(10) copies/mL) and three clinical plasma samples.
      Interlaboratory variation was observed in both actual (range, 2.0-4.0 log(10)
      copies/mL) and self-reported lower limits of detection (range, 1.0-4.0 log(10)
      copies/mL). Variation observed in reported results for individual samples ranged
      from 2.0 log(10) (minimum) to 4.3 log(10) (maximum)(.) Variation was greatest at
      low VLs. Assuming +/- 0.5 log(10) relative to the expected result represents an
      acceptable result, 57.6% of results fell within this range. Use of commercially
      available reagents and procedures was associated with less variability compared
      with laboratory-developed assays. Interlaboratory variability on replicate
      samples was significantly greater than intralaboratory variability (p < 0.0001).
      The significant interlaboratory variability in CMV VL observed may be impacting
      patient care and limiting interinstitutional comparisons. The creation of an
      international reference standard for CMV VL assay calibration would be an
      important step in quality improvement of this laboratory tool.

PMID- 19178414
TI  - Interlaboratory comparison of epstein-barr virus viral load assays.
AB  - To assess interlaboratory variability in qualitative and quantitative Epstein
      Barr virus (EBV) viral load (VL) testing, we distributed a panel of samples to 28
      laboratories in the USA, Canada and Europe who performed testing using
      commercially available reagents (n = 12) or laboratory-developed assays (n = 18).
      The panel included two negatives, seven constructed samples using Namalwa and
      Molt-3 cell lines diluted in plasma (1.30-5.30 log(10) copies/mL) and three
      clinical plasma samples. Significant interlaboratory variation was observed for
      both actual (range 1.30-4.30 log(10) copies/mL) and self-reported (range, 1.70
      3.30 log(10) copies/mL) lower limits of detection. The variation observed in
      reported results on individual samples ranged from 2.28 log(10) (minimum) to 4.14
      log(10) (maximum). Variation was independent of dynamic range and use of
      commercial versus laboratory-developed assays. Overall, only 47.0% of all results
      fell within acceptable standards of variation: defined as the expected result +/-
      0.50 log(10). Interlaboratory variability on replicate samples was significantly
      greater than intralaboratory variability (p < 0.0001). Kinetics of change in VL
      appears more relevant than absolute values and clinicians should understand the
      uncertainty associated with absolute VL values at their institutions. The
      creation of an international reference standard for EBV VL assay calibration
      would be an initial important step in quality improvement of this laboratory
      tool.

PMID- 19178415
TI  - Outcomes and utilization of kidneys from deceased donors with acute kidney
      injury.
AB  - Utilization and long-term outcomes of kidneys from donors with elevated terminal
      serum creatinine (sCr) levels have not been reported. Using data from the
      Scientific Registry of Transplant Recipients from 1995 to 2007, recipient
      outcomes of kidneys from adult donors were evaluated stratified by standard
      criteria (SCD; n = 82 262) and expanded criteria (ECD; n = 16 978) donor type and
      by sCr </=1.5, 1.6-2.0 and >2.0 mg/dL. Discard rates for SCDs were ascertained.
      The relative risk of graft loss was similar for recipients of SCD kidneys with
      sCr of 1.6-2.0 and >2.0 mg/dL, compared to </=1.5 mg/dL. For ECD recipients, the
      relative risk of graft failure significantly increased with increasing sCr. Of
      potential SCDs, the adjusted risk of discard was higher with sCr >2.0 mg/dL
      (adjusted odds ratio [AOR] 7.04, 95% confidence interval [CI] 6.5-7.6) and 1.6
      2.0 mg/dL (AOR 2.7; CI 2.5-2.9) relative to sCr </=1.5 mg/dL. Among potential
      SCDs, elevated terminal creatinine is a strong independent risk factor for kidney
      discard; yet, when kidney transplantation is performed elevated donor terminal
      creatinine is not a risk factor for graft loss. Further research is needed to
      identify safe practices for the optimal utilization of SCD kidneys from donors
      with acute kidney injury.

PMID- 19178416
TI  - Current kidney allocation rules and their impact on a pediatric transplant
      center.
AB  - In 2005, kidney allocation rules in the United States were updated to enhance
      access to kidneys from young adult deceased donors (DDs) for pediatric
      recipients. We studied how this rule change affected transplant activity at our
      pediatric center. We retrospectively compared kidney transplant activity at our
      center since the rule change (until December 31, 2007) to before the change (n =
      36 each), focusing on those recipients directly affected by it, that is, younger
      than 18 years. There were no significant differences in recipients' age, gender
      or ethnicity before versus after the rule change. Percentages of preemptive
      transplants and retransplants were similar in both groups, as was the percentage
      of sensitized patients. There was a significant decrease in overall, but not DD,
      mean donor age. Mean wait time for DD kidneys decreased for pediatric recipients.
      Increases were found in percentage of DD transplants and in mean HLA mismatches
      after the rule change. Patient and short-term graft survival were not
      significantly different. These data suggest that the allocation rule change was
      not only followed by improvement in overall access to kidney transplantation for
      children, but also by decreases in living donor transplants and HLA matching.
      Larger studies are needed to evaluate the long-term impact of the change.

PMID- 19178417
TI  - Death from metastatic donor-derived ovarian cancer in a male kidney transplant
      recipient.
AB  - Posttransplant malignancy developing in an allograft is an uncommon complication
      of organ transplantation. The tumor may represent malignant transformation of
      donor or recipient cells that were previously normal, metastatic malignancy of
      recipient origin or malignancy transmitted from organ donor to recipient.
      Establishing the origin of the malignancy is critical to treatment algorithms. It
      is generally believed allograft removal and immunosuppression withdrawal will
      lead to resolution of transmitted malignancies in cases where the renal allograft
      is the origin. We report a male patient who developed metastatic ovarian
      malignancy secondary to donor transmission.

PMID- 19178419
TI  - Comment on 'Tolerance versus immunosuppression: a perspective'.

PMID- 19178432
TI  - A linkage map of the porcine genome from a large-scale White Duroc x Erhualian
      resource population and evaluation of factors affecting recombination rates.
AB  - A porcine genome linkage map composed of 194 microsatellite markers was
      constructed with a large-scale White Duroc x Erhualian resource population. The
      marker order on this linkage map was consistent with the USDA-MARC reference map
      except for two markers on SSC3, two markers on SSC13 and two markers on SSCX. The
      length of the sex-averaged map (2344.9 cM) was nearly the same as that of the
      USDA-MARC and NIAI map. Highly significant heterogeneity in recombination rates
      between sexes was observed. Except for SSC1 and SSC13, the female autosomes had
      higher average recombination rates than the male autosomes. Moreover,
      recombination rates in the pseudoautosomal region were greater in males than in
      females. These observations are consistent with those of previous reports. The
      recombination rates on each paternal and maternal chromosome of F(2) animals were
      calculated. Recombination rates were not significantly affected by the age (in
      days) or parity of the F(1) animals. However, recombination rates on paternal
      chromosomes were affected by the mating season of the F(1) animals. This could
      represent an effect of environmental temperature on spermatogenesis.

PMID- 19178435
TI  - From apheresis for the preparation of ventricular assist devices and
      transplantation to combination therapy of apheresis and ventricular assist
      devices for myocardial repair.

PMID- 19178434
TI  - Testing for genetic association with constrained models using triads.
AB  - It has been shown that it is preferable to use a robust model that incorporated
      constraints on the genotype relative risk rather than rely on a model that
      assumes the disease operates in a recessive or dominant fashion. Previous methods
      are applicable to case-control studies, but not to family based studies of case
      children along with their parents (triads). We show here how to implement
      analogous constraints while analyzing triad data. The likelihood, conditional on
      the parents genotype, is maximized over the appropriately constrained parameter
      space. The asymptotic distribution for the maximized likelihood ratio statistic
      is found and used to estimate the null distribution of the test statistics. The
      properties of several methods of testing for association are compared by
      simulation. The constrained method provides higher power across a wide range of
      genetic models with little cost when compared to methods that restrict to a
      dominant, recessive, or multiplicative model, or make no modeling restriction.
      The methods are applied to two SNPs on the methylenetetrahydrofolate reductase
      (MTHFR) gene with neural tube defect (NTD) triads.

PMID- 19178436
TI  - Changes in gene expression during the formation of bioengineered heart muscle.
AB  - A three-dimensional bioengineered heart muscle (BEHM) construct model had been
      previously developed, exhibiting contractile forces up to 800 microN. The
      interest of this study was to determine gene expression levels of biologic
      markers involved in calcium-handling between BEHM, cell monolayer, and neonatal
      heart. Cardiac cells were isolated from one litter of F344 rats and organized
      into groups (n = 5): 4-, 7-, 10-day BEHM and cell monolayer; BEHM was evaluated
      for cell viability and contractility. Groups were then analyzed for mRNA
      expression of calcium-handling proteins: myosin heavy chain (MHC) alpha and beta,
      Sarcoplasmic reticulum Ca++ ATPase (SERCA) 2, phospholamban (PBL), and ryanodine
      receptor. BEHM exhibited electrically stimulated active force (208 +/- 12 microN
      day 4, 361 +/- 22 microN day 7, and 344 +/- 29 microN day 10) and no decrease in
      cell number. Real-time polymerase chain reaction (PCR) showed an increase in gene
      expression of all calcium-handling proteins in BEHM at 7 and 10 days compared
      with monolayers, for example, comparing BEHM to monolayer (7 and 10 days,
      respectively), MHC-alpha: 2600-fold increase and a 100-fold increase; MHC-beta:
      70-fold increase at 10 days; ryanodine receptor: 74-fold increase at 10 days;
      SERCA: 19-fold increase and sixfold increase; PBL: 158-fold increase and 24-fold
      increase. It was concluded that a three-dimensional environment is a better
      culturing condition of cardiac cells than a monolayer. Also, BEHM constructs
      demonstrated a high similarity to a native myocardium, and is, thus, a good
      starting foundation for engineered heart muscle.

PMID- 19178437
TI  - Design of fibrin matrix composition to enhance endothelial cell growth and
      extracellular matrix deposition for in vitro tissue engineering.
AB  - Tissue-engineered blood vessel substitutes should closely resemble native vessels
      in terms of structure, composition, mechanical properties, and function.
      Successful cardiovascular tissue engineering requires optimization of in vitro
      culture environment that would produce functional constructs. The extracellular
      matrix (ECM) protein elastin plays an essential role in the cardiovascular system
      to render elasticity to blood vessel wall, whereas collagen is responsible for
      providing mechanical strength. The objective of this study was to understand the
      significance of various ECM components on endothelial cell (EC) growth and tissue
      generation. We demonstrate that, even though fibrin is a good matrix for EC
      growth, fibronectin is the crucial component of the fibrin matrix that enhances
      EC adhesion, spreading, and proliferation. Vascular EC growth factor is known to
      influence in vitro growth of EC, but, so far, ECM deposition in in vitro culture
      has not been reported. In this study, it is shown that incorporation of a mixture
      of hypothalamus-derived angiogenic growth factors with fibrin matrix enhances
      synthesis and deposition of insoluble elastin and collagen in the matrix, within
      10 days of in vitro culture. The results suggest that a carefully engineered
      fibrin composite matrix may support EC growth, survival, and remodeling of ECM in
      vitro and impart optimum properties to the construct for resisting the shear
      stress at the time of implantation.

PMID- 19178438
TI  - A novel approach to align adult neural stem cells on micropatterned conduits for
      peripheral nerve regeneration: a feasibility study.
AB  - There is a strong need for nerve-tissue engineering using the guide conduit and
      Schwann cells or neural stem cells (NSCs) with regeneration potential for injured
      peripheral nerves. In this study, micropatterned poly(D,L-lactide) (PLA) conduits
      were fabricated by microlithography and solvent-casting. The PLA conduits were
      seeded with the novel green fluorescent protein (GFP)-positive adult mouse NSCs
      obtained using the patented method of one of the authors. About 85% of the seeded
      NSCs were successfully aligned on the micropatterned conduits within 72 h and
      expressed the genes related to the production of neurotrophic factors. Gene
      expressions for the neurotrophic factors, such as nerve growth factor and brain
      derived neurotrophic factor were upregulated by the micropatterned conduits at 72
      h. The micropatterned PLA conduits seeded with the aligned NSCs were used to
      bridge the 10-mm sciatic nerve gaps in rats and were found to facilitate nerve
      repair and functional recovery during a period of 6 weeks compared with the
      nonseeded group. This model can be used to study the role of adult NSCs in
      peripheral-nerve regeneration in the future.

PMID- 19178439
TI  - Functional and biocompatibility performances of an integrated Maglev pump
      oxygenator.
AB  - To provide respiratory support for patients with lung failure, a novel compact
      integrated pump-oxygenator is being developed. The functional and
      biocompatibility performances of this device are presented. The pump-oxygenator
      is designed by combining a magnetically levitated pump/rotor with a uniquely
      configured hollow fiber membrane bundle to create an assembly free, ultracompact,
      all-in-one system. The hemodynamics, gas transfer and biocompatibility
      performances of this novel device were investigated both in vitro in a
      circulatory flow loop and in vivo in an ovine animal model. The in vitro results
      showed that the device was able to pump blood flow from 2 to 8 L/min against a
      wide range of pressures and to deliver an oxygen transfer rate more than 300
      mL/min at a blood flow of 6 L/min. Blood damage tests demonstrated low hemolysis
      (normalized index of hemolysis [NIH] approximately 0.04) at a flow rate of 5
      L/min against a 100-mm Hg afterload. The data from five animal experiments (4 h
      to 7 days) demonstrated that the device could bring the venous blood to near
      fully oxygen-saturated condition (98.6% +/- 1.3%). The highest oxygen transfer
      rate reached 386 mL/min. The gas transfer performance was stable over the study
      duration for three 7-day animals. There was no indication of blood damage. The
      plasma free hemoglobin and platelet count were within the normal ranges. No gross
      thrombus is found on the explanted pump components and fiber surfaces. Both in
      vitro and in vivo results demonstrated that the newly developed pump-oxygenator
      can achieve sufficient blood flow and oxygen transfer with excellent
      biocompatibility.

PMID- 19178440
TI  - Experimental setup to evaluate the performance of percutaneous pulmonary valved
      stent in different outflow tract morphologies.
AB  - Percutaneous pulmonary valve implantation is a potential treatment for right
      ventricular outflow tract (RVOT) dysfunction. However, RVOT implantation site
      varies among subjects and the success of the procedure depends on RVOT morphology
      selection. The aim of this study was to use in vitro testing to establish
      percutaneous valve competency in different previously defined RVOT morphologies.
      Five simplified RVOT geometries (stenotic, enlarged, straight, convergent, and
      divergent) were manufactured by silicone dipping. A mock bench was developed to
      test the percutaneous valve in the five different RVOTs. The bench consists of a
      volumetric pulsatile pump and of a hydraulic afterload. The pump is made of a
      piston driven by a low inertia programmable motor. The hydraulic afterload mimics
      the pulmonary input impedance and its design is based on a three element model of
      the pulmonary circulation. The mock bench can replicate different physiological
      and pathological hemodynamic conditions of the pulmonary circulation. The mock
      bench is here used to test the five RVOTs under physiological-like conditions:
      stroke volume range 40-70 mL, frequency range 60-80 bpm. The valved stent was
      implanted into the five different RVOT geometries. Pressures upstream and
      downstream of the valved stent were monitored. Flow rates were measured with and
      without the valved stent in the five mock RVOTs, and regurgitant fraction
      compared between the different valved stent RVOTs. The percutaneous valved stent
      drastically reduced regurgitant flow if compared with the RVOT without the valve.
      RVOT geometry did not significantly influence the flow rate curves. Mean
      regurgitant fractions varied from 5% in the stenotic RVOT to 7.3% in the straight
      RVOT, highlighting the influence of the RVOT geometry on valve competency. The
      mock bench presented in this study showed the ability to investigate the
      influence of RVOT geometry on the competence of valved stent used for
      percutaneous pulmonary valve treatment.

PMID- 19178441
TI  - Lumbar stimulation belt for therapy of low-back pain.
AB  - We developed the STIMBELT, an electrical stimulation system that comprises a
      lumbar belt with up to eight pairs of embedded electrodes and an eight-channel
      electronic stimulator. The STIMBELT is an assistive system for the treatment of
      low-back pain (LBP). We describe here technical details of the system and
      summarize the results of its application in individuals with subacute and chronic
      LBP. The direct goals of the treatment were to relieve pain, reduce muscle
      spasms, increase strength and range of motion, and educate individuals with LBP
      in reducing the chances of its reoccurrence. The outcome measures include: a
      Visual Analogue Scale (VAS), the Oswestry LBP Disability Questionnaire, the Short
      Form (SF)-12 health survey, and the Manual Muscle Test. The results indicate
      significant benefits for individuals who use the STIMBELT in addition to the
      conventional therapy as opposed to only the conventional therapy.

PMID- 19178442
TI  - Economic, social, and psychological factors associated with health-related
      quality of life of chronic hemodialysis patients in northern Taiwan: a
      multicenter study.
AB  - This study evaluated the associations between economic, social, psychological
      factors, and health-related quality of life of hemodialysis patients. Cross
      sectional study design was used. End-stage renal disease patients who had
      received maintenance hemodialysis for more than 2 months at 14 centers in
      northern Taiwan were invited to participate. Demographic, economic, and
      psychosocial data of patients were collected. Depression was assessed by the Beck
      Depression Inventory. Health-related quality of life was measured by the Medical
      Outcomes Study Short-Form 36. Multivariable linear regression analyses were
      performed. Eight hundred sixty-one patients (373 males, mean age 59.4 +/- 13.2
      years) completed the study. Higher monthly income was positively associated with
      role emotional and mental health (P < 0.05), and so was increased frequency of
      social activities with social functioning (P < 0.05). The more worries, the
      stronger the inverse associations with social functioning (P < 0.05) and mental
      health (P < 0.01). Higher depression scores were associated with lower scores of
      all Short-Form 36 dimensions (P < 0.01). Higher monthly income and increased
      social activities are associated with better health-related quality of life,
      whereas more worries and higher depression scores are associated with worse
      health-related quality of life of hemodialysis patients.

PMID- 19178443
TI  - Quantitative analysis of pulsatile flow contribution to ultrafiltration.
AB  - We evaluated the quantitative contribution of pulsatile flow to ultrafiltration
      (UF) in terms of fluid power, membrane stretch, and reduction of membrane
      layering. An in vitro comparison of the UF rate using pulsatile and roller pumps
      was performed with distilled water and bovine whole blood. The mean transmembrane
      pressure (TMPm) and UF rate were higher with the pulsatile pump for the same mean
      flow rate: 6.6 mm Hg and 21.1 mL/min higher on average for distilled water and
      34.2 mm Hg and 31.4 mL/min higher on average for blood. The average UF rate was
      8.4 mL/min higher with the pulsatile pump for the same TMPm with bovine blood.
      However, the relationship between the UF rate and the TMPm was independent of the
      flow configuration for distilled water. We showed that the higher UF rate in the
      pulsatile pump is mainly due to greater fluid power and reduction of membrane
      layering, while the membrane stretch was not an important factor.

PMID- 19178444
TI  - Photocrosslinkable chitosan hydrogel can prevent bone formation in both rat skull
      and fibula bone defects.
AB  - UV light irradiation to a photocrosslinkable chitosan (Az-CH-LA) resulted in an
      insoluble and flexible hydrogel within 30 s. The purpose of this study was to
      evaluate the ability of the photocrosslinkable chitosan to inhibit bone formation
      in the bone defects. A 5-mm-diameter defect was made in the rat calvarium, and
      then photocrosslinkable chitosan was implanted and irradiated with UV for 30 s.
      Furthermore, a 2-mm defect was made in the fibula of a rat hind leg, and then
      photocrosslinkable chitosan was implanted and irradiated with UV. Bone formations
      in the rat skull and fibula defects with photocrosslinkable chitosan hydrogel
      were significantly prevented for 8 weeks. Thus, the chitosan hydrogel has an
      inhibitory effect on bone formation.

PMID- 19178445
TI  - Coronary hemodynamics and myocardial oxygen consumption during support with
      rotary blood pumps.
AB  - Mechanical support offered by rotary pumps is increasingly used to assist the
      failing heart, although several questions concerning physiology remain. In this
      study, we sought to evaluate the effect of left-ventricular assist device (VAD)
      therapy on coronary hemodynamics, myocardial oxygen consumption, and pulmonary
      blood flow in sheep. We performed an acute experiment in 10 sheep to obtain
      invasively measured coronary perfusion data, as well as pressure and flow
      conditions under cardiovascular assistance. A DeBakey VAD (MicroMed
      Cardiovascular, Inc., Houston, TX, USA) was implanted, and systemic and coronary
      hemodynamic measurements were performed at defined baseline conditions and at
      five levels of assistance. Data were measured when the pump was clamped, as well
      as under minimum, maximum, and moderate levels of assistance, and in a pump-off
      condition where backflow occurs. Coronary flow at the different levels of support
      showed no significant impact of pump activity. The change from baseline ranged
      from -10.8% to +4.6% (not significant [n.s.]). In the pulmonary artery, we
      observed a consistent increase in flow up to +4.5% (n.s.) and a decrease in the
      pulmonary artery pressure down to -14.4% (P = 0.004). Myocardial oxygen
      consumption fell with increasing pump support down to -34.6% (P = 0.008). Left
      ventricular pressure fell about 52.2% (P = 0.016) as support was increased. These
      results show that blood flow in the coronary arteries is not affected by flow
      changes imposed by rotary blood pumps. An undiminished coronary perfusion at
      falling oxygen consumption might contribute to cardiac recovery.

PMID- 19178446
TI  - The relationship between leptin level and oxidative status parameters in
      hemodialysis patients.
AB  - Both serum leptin level and oxidative stress are increased in hemodialysis (HD)
      patients. In the present study, we aimed to investigate whether there is
      association between oxidative status and leptin level in HD patients. Thirty-five
      HD patients and 25 healthy controls were enrolled in the present study. Serum
      leptin level, total peroxide (TP) level, total antioxidant capacity (TAC), and
      oxidative stress index (OSI) were determined. Serum leptin level, TP level, and
      OSI were significantly higher in HD patients than controls (all P < 0.001) while
      TAC was lower (P < 0.001). In HD patients, serum leptin level was significantly
      correlated with TP level and OSI (r = 0.372, P < 0.001 and r = 0.409, P < 0.001,
      respectively). The correlation of serum leptin level with TP level and OSI
      remained statistically significant after adjusting for age, gender, and body-fat
      percentage (r = 0.446, P < 0.001 and r = 0.463, P < 0.001, respectively).
      Hyperleptinemia seems to be associated with increased oxidative stress in HD
      patients, and this association may provide better understanding about the
      disorders related to either elevated serum leptin levels and/or increased
      oxidative stress in HD patients.

PMID- 19178447
TI  - Bioengineering of the aortic valve: a race without a finish line.

PMID- 19178449
TI  - Re: Hydrogel-based engineered skeletal muscle grafts normalize heart function
      early after myocardial infarction.

PMID- 19178450
TI  - Are we closer to the clinical use of blood substitutes?

PMID- 19178451
TI  - Artificial oxygen carriers: scientific and biotechnological points of view.

PMID- 19178452
TI  - Artificial oxygen carriers: a clinical point of view.

PMID- 19178453
TI  - Intrinsic toxicity of hemoglobin: how to counteract it.
AB  - The development of safe and effective blood substitutes is of great importance in
      both civilian and military medicine. The currently tested hemoglobin (Hb)-based
      oxygen carriers, however, have toxicity and efficacy problems. A number of
      unwanted effects have been observed in human trials, creating doubts about their
      clinical usefulness. In some subjects, vasoconstriction and decreased blood flow
      to the vital organs, heart attack, stroke, systemic inflammation, organ damage,
      and even death, have been attributed to the transfusion of these experimental
      products. Hb is a well-known pressor agent and strong oxidant, although the full
      understanding of its intrinsic toxicity is yet to be uncovered. In particular,
      the complete mechanism of Hb-induced vasoconstriction needs full elucidation.
      Knowledge of the biological events that trigger the induction of genes upon
      treatment with redox-active Hb, as well as its catabolism, is still incomplete.
      It seems that our limited knowledge of free Hb effects in vivo is the main reason
      for not yet having a viable substitute of human blood. The future for universal
      red cell substitutes is in the new-generation products that address all of Hb's
      intrinsic toxicity issues.

PMID- 19178454
TI  - Radical producing and consuming reactions of hemoglobin: how can we limit
      toxicity?
AB  - Hemoglobin has a range of enzymatic activities that can affect its putative
      pharmacological role as an extracellular oxygen carrier. In the presence of
      peroxides, deoxyhemoglobin and methemoglobin can produce free radicals and induce
      lipid peroxidation. Oxyhemoglobin can oxidize the free radical nitric oxide to
      nitrate, yet deoxyhemoglobin can produce nitric oxide from nitrite. These
      enzymatic reactions can induce or diminish toxic side reactions when hemoglobin
      is added in vivo. For example the removal of the free radical vasodilator nitric
      oxide, or the addition of the lipid-derived vasoconstrictor F2-isoprostane, will
      both alter blood flow and blood pressure. In order to determine the dominant
      effects it is necessary to design molecules with differing radical reactivities.
      Molecules have been designed with these modifications and this article will
      review their role in determining mechanism as well as their possible
      functionality as blood substitutes.

PMID- 19178456
TI  - Possible role of artificial oxygen carriers in transfusion medicine: a
      retrospective analysis on the current transfusion practice.
AB  - Artificial oxygen carriers (AOC) are under development as a substitute for red
      blood cells (RBC) in homologous transfusion (Tx). The lack of surface antigen in
      AOC makes ABO-typing and antibody-screening (T/S) unnecessary. Pathogen
      elimination renders it much safer, and long-term stability allows ubiquitous
      storage for emergency use. To delineate the utility of AOC, we retrospectively
      examined current Tx practices in Tokai University and the Japanese Red Cross
      Society. The emergency department of Tokai University Hospital has been using
      O(+)Rh(+) RBC in patients with hemorrhagic shock before Tx becomes available.
      Those who received the RBCs within 60 min of injury had a significantly higher
      survival rate than those who received it later (> or =60 min). The Red Cross
      Blood Center provided 411 units of RBC for 138 urgent requests for rare blood
      types. Our analysis suggests that if an AOC were available for the initial six
      units, 96% of such requests could have been covered to avoid urgent donor
      allocation, preparation, and Tx. Among 2079 surgical cases who ordered T/S, only
      29% actually required Tx, rendering >70% of the T/S unnecessary. Because only
      7.4% required nine units or more, more than 92% of T/S and Tx could have been
      avoided in retrospect if an AOC were available for the initial eight units. The
      results suggest that an AOC might be useful in various situations to alleviate
      problems, concerns, and technical burden in the current Tx practices. Because the
      expected utility is based mainly on physical characteristics, AOC may remain
      advantageous even when biogenetically derived RBC becomes available.

PMID- 19178455
TI  - Control of oxidative reactions of hemoglobin in the design of blood substitutes:
      role of the ascorbate-glutathione antioxidant system.
AB  - Uncontrolled oxidative reactions of hemoglobin (Hb) are still the main unresolved
      problem for Hb-based blood substitute developers. Spontaneous oxidation of
      acellular ferrous Hb into a nonfunctional ferric Hb generates superoxide anion.
      Hydrogen peroxide, formed after superoxide anion dismutation, may react with
      ferrous/ferric Hb to produce toxic ferryl Hb, fluorescent heme degradation
      products, and/or protein-based free radicals. In the presence of free iron
      released from heme, superoxide anion and hydrogen peroxide might react via the
      Haber-Weiss and Fenton reactions to generate the hydroxyl radical. These highly
      reactive oxygen and heme species may not only be involved in shifting the
      cellular redox balance to the oxidized state that facilitates signal transduction
      and pro-inflammatory gene expression, but could also be involved in cellular and
      organ injury, and generation of vasoactive compounds such as isoprostanes and
      angiotensins. It is believed that these toxic species may be formed after
      administration of Hb-based blood substitutes, particularly in ischemic patients
      with a diminished ability to control oxidative reactions. Although varieties of
      antioxidant strategies have been suggested, this in vitro study examined the
      ability of the ascorbate-glutathione antioxidant system in preventing Hb
      oxidation and formation of its ferryl intermediate. The results suggest that
      although ascorbate is effective in reducing the formation of ferryl Hb,
      glutathione protects heme against excessive oxidation. Ascorbate without
      glutathione failed to protect the red blood cell membranes against Hb/hydrogen
      peroxide-mediated peroxidation. This study provides evidence that the ascorbate
      glutathione antioxidant system is essential in attenuation of the pro-oxidant
      potential of redox active acellular Hbs, and superior to either ascorbate or
      glutathione alone.

PMID- 19178457
TI  - Hemospan: design principles for a new class of oxygen therapeutic.
AB  - Hemoglobin-based oxygen carriers have been under development for decades, but
      safety concerns have prevented commercial approval. Early designs for modified
      hemoglobins by polymerization or intramolecular cross-linking reactions increased
      molecular size and decreased oxygen affinity, but all exhibited side effects of
      vasoconstriction and reduced blood flow. A new strategy has been established by
      applying principles of oxygen transport to cell-free hemoglobin. Sangart has
      developed a new oxygen therapeutic, Hemospan, using site-specific, poly(ethylene)
      glycol conjugation chemistry designed on two principles: (i) increased
      macromolecular size to prolong intravascular retention time, and (ii) increased
      oxygen affinity to prevent premature oxygen offloading in arterioles. In contrast
      to early-generation products, Hemospan infusion maintains normal arteriolar
      vascular tone and capillary flow. Phase I and Phase II clinical trials have been
      completed, showing that Hemospan is well-tolerated in humans, with evidence of
      efficacy to impart hemodynamic stability in surgical patients under anesthesia.
      Phase III trials in orthopedic surgery have recently completed enrollment in
      Europe.

PMID- 19178458
TI  - Review of hemoglobin-vesicles as artificial oxygen carriers.
AB  - Blood transfusion systems have greatly benefited human health and welfare.
      Nevertheless, some problems remain: infection, blood type mismatching,
      immunological response, short shelf life, and screening test costs. Blood
      substitutes have been under development for decades to overcome such problems.
      Plasma component substitutes have already been established: plasma expanders,
      electrolytes, and recombinant coagulant factors. Herein, we focus on the
      development of red blood cell (RBC) substitutes. Side effects hindered early
      development of cell-free hemoglobin (Hb)-based oxygen carriers (HBOCs) and
      underscored the physiological importance of the cellular structure of RBCs. Well
      designed artificial oxygen carriers that meet requisite criteria are expected to
      be realized eventually. Encapsulation of Hb is one idea to shield the toxicities
      of molecular Hbs. However, intrinsic issues of encapsulated Hbs must be resolved:
      difficulties related to regulating the molecular assembly, and management of its
      physicochemical and biochemical properties. Hb-vesicles (HbV) are a cellular type
      of HBOC that overcome these issues. The in vivo safety and efficacy of HbV have
      been studied extensively. The results illustrate the potential of HbV as a
      transfusion alternative and promise its use for other clinical applications that
      remain unattainable using RBC transfusion.

PMID- 19178459
TI  - Liposome-Encapsulated Hemoglobin, TRM-645: Current Status of the Development and
      Important Issues for Clinical Application.
AB  - Clinical application of artificial oxygen carriers as a substitute for blood
      transfusion has long been expected to solve some of the problems associated with
      blood transfusion. Use for oxygen delivery treatment for ischemic disease by
      oxygen delivery has also been examined. These prospective applications of
      artificial oxygen carriers are, however, still in development. We have developed
      liposome-encapsulated hemoglobin (LEH), developmental code TRM-645, using
      technologies for encapsulation of concentrated hemoglobin (Hb) with high
      encapsulation efficiency as well as surface modification to achieve stability in
      circulating blood and a long shelf life. We have confirmed the basic efficacy and
      safety of TRM-645 as a red blood cell substitute in studies on the efficacy of
      oxygen delivery in vivo, and the safety of TRM-645 has been studied in some
      animal species. We are now examining various issues related to clinical studies,
      including further preclinical studies, management of manufacturing and the
      quality assurance for the Hb solution and liposome preparations manufactured by
      the GMP facility.

PMID- 19178460
TI  - Liposome-encapsulated hemoglobin alleviates brain edema after permanent occlusion
      of the middle cerebral artery in rats.
AB  - Liposome-encapsulated hemoglobin (LEH) was proven to be protective in cerebral
      ischemia/reperfusion injury. The present study evaluated LEH in a rat model of
      permanent middle cerebral artery (MCA) occlusion to clarify its effect during
      ischemia and reperfusion. Five minutes after thread occlusion of the MCA, rats
      were infused with 10 mL/kg of LEH (LEH, n = 13), and compared with normal
      controls (n = 11). Additional animals received the same MCA occlusion with no
      treatment (CT, n = 11), saline (saline, n = 10), empty liposome solution (EL, n =
      13), or washed red blood cells (RBC, n = 7). Severity of brain edema was
      determined 24 h later by signal strength in T2-weighted magnetic resonance
      imaging of the cortex, striatum, hippocampus, and pyriform lobe. The results
      showed that brain edema/infarction observed in any vehicle-infused control was
      significantly more severe than in LEH-treated rats. There was a tendency toward
      aggravated edema in rats receiving ELs. LEH infusion at a dose of 10 mL/kg
      significantly reduced edema formation as compared to other treatments in a wide
      area of the brain 24 h after permanent occlusion of the MCA. Low oncotic pressure
      of EL and LEH solution (vehicle solution) appeared to cause nonsignificant
      aggravation of edema and reduced protective effects of LEH.

PMID- 19178461
TI  - Liposome-encapsulated hemoglobin reduces the size of cerebral infarction in rats:
      effect of oxygen affinity.
AB  - Liposome-encapsulated hemoglobin (LEH) with a low oxygen affinity (l-LEH, P(50) =
      45 mm Hg) was found to be protective in the rodent and primate models of ischemic
      stroke. This study investigated the role of LEH with a high O(2) affinity (h-LEH,
      P(50) = 10 mm Hg) in its protective effect on brain ischemia. The extent of
      cerebral infarction was determined 24 h after photochemically induced thrombosis
      of the middle cerebral artery from the integrated area of infarction detected by
      triphenyltetrazolium chloride staining in rats receiving various doses of h-LEH
      as well as l-LEH. Both h-LEH and l-LEH significantly reduced the extent of
      cortical infarction. h-LEH remained protective at a lower concentration (minimal
      effective dose [MED]: 0.08 mL/kg) than l-LEH (MED: 2 mL/kg) in the cortex. h-LEH
      reduced the infarction extent in basal ganglia as well (MED: 0.4 mL/kg), whereas
      l-LEH provided no significant protection. h-LEH provided better protection than l
      LEH. The protective effect of both high- and low-affinity LEH may suggest the
      importance of its small particle size (230 nm) as compared to red blood cells.
      The superiority of h-LEH over l-LEH supports an optimal O(2) delivery to the
      ischemic penumbra as the mechanism of action in protecting against brain ischemia
      and reperfusion.

PMID- 19178462
TI  - In vivo distribution of liposome-encapsulated hemoglobin determined by positron
      emission tomography.
AB  - Positron emission tomography (PET) is a noninvasive imaging technology that
      enables the determination of biodistribution of positron emitter-labeled
      compounds. Lipidic nanoparticles are useful for drug delivery system (DDS),
      including the artificial oxygen carriers. However, there has been no appropriate
      method to label preformulated DDS drugs by positron emitters. We have developed a
      rapid and efficient labeling method for lipid nanoparticles and applied it to
      determine the movement of liposome-encapsulated hemoglobin (LEH). Distribution of
      LEH in the rat brain under ischemia was examined by a small animal PET with an
      enhanced resolution. While the blood flow was almost absent in the ischemic
      region observed by [(15)O]H(2)O imaging, distribution of (18)F-labeled LEH in the
      region was gradually increased during 60-min dynamic PET scanning. The results
      suggest that LEH deliver oxygen even into the ischemic brain from the periphery
      toward the core of ischemia. The real-time observation of flow pattern,
      deposition, and excretion of LEH in the ischemic rodent brain was possible by the
      new methods of positron emitter labeling and PET system with a high resolution.

PMID- 19178463
TI  - Effects of liposome-encapsulated hemoglobin on human immune system: evaluation in
      immunodeficient mice reconstituted with human cord blood stem cells.
AB  - As preclinical evaluation in animals does not necessarily portray human
      responses, liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier,
      was tested in immunodeficient mice reconstituted with human hematopoietic stem
      cells (cord blood-transfused NOD/SCID/IL-2R(gammanull)[CB-NOG] mice). Changes in
      immunocompetent T-cell and B-cell composition in peripheral blood, spleen, and
      bone marrow were examined 2 and 7 days after 10 mL/kg of intravenous
      administration of LEH, empty liposome (EL), or saline using immunohistochemical
      and flow cytometrical techniques in wild-type mice and CB-NOG mice. Responses to
      intraperitoneal administration of toxic shock syndrome toxin-1 (TSST-1) under the
      absence or presence of LEH (10 mL/kg) were also determined 4 h and 3 days later
      in terms of lymphocyte composition and IL-2 plasma level in wild-type as well as
      CB-NOG mice. When liposome (LEH or EL) was administered to wild-type or CB-NOG
      mice, the composition of B-cells and T-cells in the spleen or peripheral blood
      failed to show any consistent or significant changes. The responses to a
      bacterial antigen (TSST-1) measured by IL-2 production were comparable regardless
      of the presence or absence of LEH in wild-type as well as in CB-NOG mice.
      Cellularity, distribution, and maturation of these human cells in peripheral
      blood, spleen, and bone marrow were comparable among the groups. The results
      suggest that simple LEH administration may not change immune cellularity, and LEH
      presence may not largely affect the early T-cell response to bacterial
      enterotoxins in murine as well as in reconstituted human immune systems.

PMID- 19178464
TI  - HemoCD as an artificial oxygen carrier: oxygen binding and autoxidation.
AB  - Despite many attempts to construct completely artificial systems for carrying
      oxygen (O(2)) in aqueous solution, no successful example had been reported until
      quite recently except for picket fence porphinatoiron(II) embedded in liposomal
      membrane. We newly prepared a 1:1 complex (hemoCD) of 5,10,15,20-tetrakis(4
      sulfonatophenyl)porphinatoiron(II) (Fe[II]TPPS) and a per-O-methylated beta
      cyclodextrin dimer having a pyridine linker (Py3CD). HemoCD binds O(2) reversibly
      in aqueous solution. The oxygen affinity corresponding to the partial O(2)
      pressure, at which half of the hemoCD molecules are oxygenated, was 16.9 torr in
      phosphate buffer at pH 7.0 and 25 degrees C. Oxy-hemoCD was gradually autoxidized
      (t(1/2) = 30.1 h) due to nucleophilic attack of a water molecule to the O(2)-Fe
      bond. Encapsulation of the iron center of Fe(II)TPPS by two cyclodextrin
      truncated cones is essential for binding of O(2) to the ferrous center of the
      porphyrin. This manuscript reports the basic characteristics of hemoCD and the
      possible future utility of a totally artificial O(2) carrier.

PMID- 19178465
TI  - S-nitrosylated pegylated hemoglobin reduces the size of cerebral infarction in
      rats.
AB  - Cell-free hemoglobin-based oxygen carriers have well-documented safety and
      efficacy problems such as nitric oxide (NO) scavenging and extravasation that
      preclude clinical use. To counteract these effects, we developed S-nitrosylated
      pegylated hemoglobin (SNO-PEG-Hb, P(50) = 12 mm Hg) and tested it in a brain
      ischemia and reperfusion model. Neurological function and extent of cerebral
      infarction was determined 24 h after photochemically induced thrombosis of the
      middle cerebral artery in the rat. Infarction extent was determined from the
      integrated area in the cortex and basal ganglia detected by triphenyltetrazolium
      chloride staining in rats receiving various doses of SNO-PEG-Hb (2, 0.4, and 0.08
      mL/kg) and compared with rats receiving pegylated hemoglobin without S
      nitrosylation (PEG-Hb) or saline of the same dosage. Results indicated that
      successive dilution revealed SNO-PEG-Hb but not PEG-Hb to be effective in
      reducing the size of cortical infarction but not neurological function at a dose
      of 0.4 mL/kg. In conclusion, SNO-PEG-Hb in a dose of 0.4 mL/kg (Hb 24 mg/kg)
      showed to be most effective in reducing the size of cortical infarction, however,
      without functional improvement.

PMID- 19178466
TI  - Novel controlling mechanism of the oxygen affinity in myoglobin with isomeric
      porphyrins.
AB  - The biological function of the core modified porphyrin isomers such as
      porphycene, corrphycene, and hemiporphycene was examined. The iron complexes
      stoichiometrically coupled with apomyoglobin to afford stable holoproteins. The
      oxygen affinity of the reconstituted myoglobins (Mbs) changed over a 60 000-fold
      range depending on the molecular structure of the prosthetic groups. For
      instance, a corrphycene with electronegative substituents to the bipyrrole part
      reduced the oxygen affinity of Mb to P(50) = 300 mm Hg while the porphycene
      substituted Mb exhibited a P(50) = 0.005 mm Hg. A notable increase in the oxygen
      delivery capacity of the corrphycene-substituted Mb was explained on the basis of
      the trapezoidal corrphycene shape that stabilizes the iron displacement from the
      macrocycle plane toward the proximal histidine. The above observations
      demonstrate that the core modified heme isomers serve as novel molecular tools to
      regulate the oxygen affinity of Mb.

PMID- 19178467
TI  - Mechanical properties of tissue-engineered vascular grafts: response to letter to
      the editor.

PMID- 19178468
TI  - Development of a composite degradable/nondegradable tissue-engineered vascular
      graft.

PMID- 19178469
TI  - Commentary: Pre weaning morbidity in llamas and alpacas.

PMID- 19178470
TI  - Haematological, biochemical and selected acute phase protein reference intervals
      for weaned female Merino lambs.
AB  - BACKGROUND: Merino lambs are currently the subject of much research into the
      welfare aspects of mulesing and mulesing alternatives. OBJECTIVE: Obtain
      haematology, biochemistry and acute phase protein reference intervals using
      modern methodologies for female Merino lambs. METHOD: Blood was collected from
      50, weaned, 9- to 16-week-old, female Merino lambs. Haematology and biochemistry
      panels were performed using routine automated methods. The acute phase proteins,
      fibrinogen, serum amyloid A and haptoglobin, were also measured using
      commercially available techniques. The reference intervals were determined to be
      the central 95% of results. RESULTS: Differences in the concentrations for some
      analytes were seen when compared with reported studies in sheep, but may be
      explained by the use of sheep of a different signalment, as well as different
      methodologies for analyte measurement. Overall, most analytes gave similar values
      to those previously reported in other studies. Notable exceptions were alkaline
      phosphatase, phosphate and globulins, for which the different results were often
      attributed to the younger age of the sheep in the present study, and platelets
      and creatine kinase, for which the elevated levels may have been a result of
      stress and muscle exertion associated with blood collection and husbandry
      practices. CONCLUSION: Established haematological, biochemical and acute phase
      protein reference intervals are necessary for the investigation of the systemic
      impact of mulesing and mulesing alternatives and for the investigation of
      systemic diseases affecting weaned, 9- to 16-week-old, female Merino lambs in
      general.

PMID- 19178471
TI  - Assessment of welfare of suckling lambs following intradermal injection of
      cetrimide as a non-surgical alternative to conventional mulesing.
AB  - OBJECTIVE: To assess in suckling lambs the impact of intradermal injection of
      cetrimide, a quaternary ammonium compound formulated to induce non-surgical
      mulesing, on some physiological and behavioural indicators of welfare.
      PROCEDURES: We allocated 32 suckling lambs (9-11 weeks old) to three groups: (1)
      control (n = 10), (2) conventional surgical mules (n = 11) and (3) non-surgical
      mules (n = 11). Non-surgical mulesing was induced by intradermal injection of 4%
      (w/w) cetrimide + 3% (w/w) polyvinylpyrrolidone in water. Lambs were run in pens
      of four together with their dams. Haematology, cortisol, beta-endorphin and
      haptoglobin levels, and rectal temperature were monitored at least daily for the
      first 7 days after treatment, then weekly until day 28. Body weight was measured
      weekly and behaviour was measured every 15 min for 12 h on the day of treatment,
      then on days 1, 2, 4, 6, 12, 21 and 28 following treatment. RESULTS: The
      intradermal treatment induced local tissue swelling, systemic signs of severe
      inflammation, including high fever (> 41.0 degrees C) and elevated blood cortisol
      levels, by 12 h. Rectal temperatures were significantly elevated until 6 days
      after treatment, cortisol levels were elevated until 4 days after treatment,
      haptoglobin levels for at least 7 days after treatment and the neutrophil to
      lymphocyte ratio until 5 days after treatment. Peak cortisol values were
      comparable in mulesed lambs and lambs receiving the intradermal treatment,
      whereas the areas under the curves for cortisol and temperature were greater in
      lambs receiving the intradermal treatment than in mulesed lambs. Beta-endorphin
      levels were significantly elevated in mulesed sheep at 12 h. There was no effect
      of intradermal treatment on average daily gain, fibre diameter or beta-endorphin
      concentration. Mulesed lambs spent 44% of the time in abnormal behaviours
      (hunched standing, stiff walking, pawing, lateral lying and lying intention) on
      the day of treatment. On the day after treatment, lambs receiving the intradermal
      treatment spent 11% of the time (comparable to mulesed lambs) in abnormal
      behaviours. In comparison, control lambs spent 0.4% of their time in abnormal
      behaviours on the same day. CONCLUSIONS: The welfare of suckling lambs that were
      non-surgically mulesed by intradermal injection of cetrimide was measurably
      poorer than control lambs.

PMID- 19178472
TI  - Effect of the non-steroidal anti-inflammatory drug, carprofen, on weaned sheep
      following non-surgical mulesing by intradermal injection of cetrimide.
AB  - OBJECTIVE: To assess in weaned lambs the palliative effects of the non-steroidal
      anti-inflammatory drug, carprofen, following intradermal injection of cetrimide
      to induce non-surgical mulesing. PROCEDURES: We allocated 40 weaned lambs (20-22
      weeks old) to four groups of 10 animals: (1) control, 2) conventional surgical
      mules, (3) intradermal treatment and (4) intradermal treatment + carprofen. Non
      surgical mulesing was induced by intradermal injection of 4% (w/w) cetrimide + 3%
      (w/w) polyvinylpyrrolidone in water. In group 4, carprofen (4 mg/kg, SC) was
      administered 1 h before intradermal treatment. Five weaners, including an animal
      from each treatment, were run in each pen. Neutrophil to lymphocyte ratio,
      cortisol, beta-endorphin and haptoglobin levels and rectal temperature were
      monitored at least daily for the first 7 days after treatment, then weekly until
      day 28. Body weight was measured weekly and behaviour was measured every 15 min
      for 12 h on the day of treatment, then on days 1, 2, 4, 6, 12, 21 and 28
      following treatment. RESULTS: The intradermal treatment resulted in high fever
      and elevated blood cortisol by 12 h. Rectal temperatures were significantly
      elevated until 5 days after treatment, cortisol was elevated until 3 days after
      treatment, haptoglobin for at least 7 days after treatment and the neutrophil to
      lymphocyte ratio until 4 days after treatment. Average daily gain was depressed
      in the week following treatment. Abnormal behaviours (hunched standing, stiff
      walking, pawing, lateral lying and lying intention) were increased on the day of
      treatment and for 6 days post treatment. Carprofen reduced the time spent in
      abnormal behaviours by approximately two-thirds but did not ameliorate the
      physiological responses to the intradermal treatment. CONCLUSIONS: In weaner
      sheep, carprofen ameliorated the behavioural responses, but was unable to provide
      relief from the intense and sustained physiological responses to non-surgical
      mulesing by intradermal injection of cetrimide. Systemic side-effects may be
      unavoidable with formulations based on quaternary ammonium compounds that are
      designed to reduce the risk of fly strike in sheep by remodelling breech tissue
      through induction of tissue necrosis.

PMID- 19178473
TI  - Sulfur-associated polioencephalomalacia in cattle grazing plants in the Family
      Brassicaceae.
AB  - Polioencephalomalacia was diagnosed histologically in cattle from two herds on
      the Darling Downs, Queensland, during July-August 2007. In the first incident, 8
      of 20 18-month-old Aberdeen Angus steers died while grazing pastures comprising
      60%Sisymbrium irio (London rocket) and 40%Capsella bursapastoris (shepherd's
      purse). In the second incident, 2 of 150 mixed-breed adult cattle died, and
      another was successfully treated with thiamine, while grazing a pasture
      comprising almost 100%Raphanus raphanistrum (wild radish). Affected cattle were
      either found dead or comatose or were seen apparently blind and head-pressing in
      some cases. For both incidents, plant and water assays were used to calculate the
      total dietary sulfur content in dry matter as 0.62% and 1.01% respectively, both
      exceeding the recommended 0.5% for cattle eating more than 40% forage. Blood and
      tissue assays for lead were negative in both cases. No access to thiaminase,
      concentrated sodium ion or extrinsic hydrogen sulfide sources were identified in
      either incident. Below-median late summer and autumn rainfall followed by above
      median unseasonal winter rainfall promoted weed growth at the expense of
      wholesome pasture species before these incidents.

PMID- 19178474
TI  - Identifying obstacles to reducing the use of antibiotics to control porcine
      proliferative enteropathy.
AB  - Proliferative enteropathy (PE) is an enteric disease of pigs that results in
      diarrhoea, reduced growth rate, reduced feed conversion efficiency and sometimes
      death. A survey of 13 pig veterinary practitioners in Australia was conducted to
      determine: (1) PE control strategies (antibiotics and vaccination), (2) how the
      efficacies of these strategies are evaluated and (3) how reliance on antibiotics
      could be reduced by increasing vaccine adoption. Antibiotics were routinely
      prescribed in the diets of weaner, grower and finisher pigs by 9/13, 10/13 and
      8/13 veterinarians, respectively, if vaccination was not implemented. Water
      soluble antibiotics were prescribed less frequently than in-feed antibiotics.
      Efficacy of control strategies was assessed most often through reduced clinical
      signs (diarrhoea, 'tail-ender' pigs, death) and reduced lesion incidence at
      abattoir postmortem inspection. Twelve practitioners had recommended PE
      vaccination to their clients in the previous 6 months. Barriers to continued
      vaccine implementation included perceived lack of efficacy for pigs housed in
      bedded systems, high cost relative to medication and difficulties in vaccinating
      pigs post-weaning.

PMID- 19178475
TI  - Equine amnionitis and fetal loss: the case definition for an unrecognised cause
      of abortion in mares.
AB  - A series of abortions occurred in mares in New South Wales during 2004 that
      involved similar and unusual findings on post mortem examination of aborted
      fetuses and fetal membranes. The term Equine Amnionitis and Fetal Loss (EAFL) was
      developed to describe the condition. This form of abortion had not been
      previously recognised in Australia. The pathology alone is not specific for EAFL
      and diagnosis requires demonstration of a combination of certain pathological and
      bacteriological features. The purpose of this paper is to describe patterns
      considered consistent with EAFL cases as a working case definition for use by
      veterinarians and veterinary pathologists in identifying future cases of EAFL.
      More detailed papers are in preparation to fully describe the epidemiological,
      histopathological, and microbiological aspects of EAFL.

PMID- 19178476
TI  - Erythrocytic pyruvate kinase deficiency and AB blood types in Australian
      Abyssinian and Somali cats.
AB  - OBJECTIVE: To determine the frequency of the mutant pyruvate kinase (PK) allele,
      haematological parameters and AB blood types of Abyssinian and Somali cats in
      Australia. DESIGN: Complete blood cell and reticulocyte counts, DNA PK mutation
      testing and blood typing were performed in all cats. RESULTS: A total of 60 cats
      (36 Abyssinians, 24 Somalis) were included (37 females, 23 males). For the mutant
      PK allele, three female Somalis were homozygous (affected, 5%), 17 cats were
      heterozygous (carrier, 28%) and 40 cats tested negative (normal, 67%). Pedigree
      analysis revealed common ancestry of affected and many carrier cats. Of affected
      cats, two had regenerative anaemias and all had reticulocytosis (range 64-390 x
      10(9)/L; P < 0.001 compared with normal or carrier cats). The only consistent
      historical sign was lethargy. One affected cat was euthanased 18 months after
      testing, because of anaemia, neutropenia, anorexia and weight loss. The mutant
      allele frequency was 0.19 overall (0.29 in Somalis, 0.13 in Abyssinians). All
      cats had blood type A. The commercial blood typing card method incorrectly
      identified 12 cats as having type AB blood. CONCLUSIONS: The frequency of the
      mutant PK allele is high in Australia. Screening for PK deficiency is indicated
      before mating and in individual cats of these breeds, even in the absence of
      anaemia and especially when there is reticulocytosis. Although all cats in the
      present study had blood type A, blood type B is common in these breeds worldwide.
      Retyping of any AB typed cats by a laboratory technique is recommended.

PMID- 19178479
TI  - Osteosarcoma of the penile bone (os penis) in a dog.
AB  - Osteosarcoma of the penile bone was diagnosed in a 5-year-old neutered male
      Rottweiler with recurrent dysuria. Imaging and cytological findings raised the
      suspicion for an osteosarcoma and ablation of the entire penis and scrotal
      urethrostomy was performed. The diagnosis was confirmed histologically. The dog
      recovered well and no postoperative signs of dysuria were observed. The dog
      survived without adjuvant chemotherapy for 12 months when multiple tumours in the
      thorax and abdomen led to it being euthanased. Penile osteosarcoma is a rare
      disease, but must be considered as a differential diagnosis in dogs presenting
      with dysuria. This is the second recorded case of a penile osteosarcoma in a dog,
      but the first with a detailed description of the diagnosis, treatment and
      outcome.

PMID- 19178477
TI  - Clinical diagnosis and treatment of suspected neuropathic pain in three dogs.
AB  - Three dogs were referred to The Queen's Veterinary School Hospital at University
      of Cambridge for chronic behavioural or locomotor disorders associated with pain.
      All three had been unsuccessfully treated with conventional analgesics, including
      non-steroidal anti-inflammatory drugs, glucocorticoids and opiate agonists, prior
      to referral, with minimal or no response. They were investigated by neurological
      examination plus conventional ancillary diagnostic tests and therapeutic drug
      trials. Ruling out other causes of pain and applying previously well-described
      criteria, each case was diagnosed as consistent with neuropathic pain, a poorly
      recognised condition in domestic dogs. Treatment with the tricyclic
      antidepressant drug, amitriptyline, or the antiepileptic drug, gabapentin,
      resulted in either a dramatic improvement or full resolution of clinical signs in
      all cases.

PMID- 19178480
TI  - Pre-weaning morbidity and mortality of llamas and alpacas.
AB  - OBJECTIVES: To describe the morbidity and mortality patterns and identify factors
      associated with morbidity in pre-weaning llamas and alpacas. DESIGN: Cross
      sectional observational study of 287 crias born on four farms in Ohio, USA.
      PROCEDURE: Historical data representing all crias born over a 6-year period were
      obtained from two llama farms and two alpaca farms in Ohio. Multivariable
      generalised linear mixed effects regression models were used to identify factors
      associated with morbidity outcomes. RESULTS: In total, 105 (37%) of the llamas
      and alpacas had some reported morbidity during the pre-weaning period, and
      mortality rate was 2.1%. In addition, 51 (18%) of llamas and alpacas experienced
      morbidity because of infectious disease, and 47 (16%) experienced morbidity
      during the neonatal period. The three most commonly reported morbidity events
      were undifferentiated diarrhoea (23%), umbilical hernia (16%) and unspecified
      infectious disease (15%). Difficult birth was an important risk factor for pre
      weaning morbidity in this population. CONCLUSIONS: Camelid veterinarians and
      their clients can expect that pre-weaning health events are common among crias,
      although mortality is low. Crias experiencing difficult births may require
      additional monitoring for health events during the pre-weaning period.

PMID- 19178481
TI  - Unidentified microsporidian in western pygmy perch Edelia vittata (Nannopercidae)
      from Australia.
AB  - Specimens of western pygmy perch, Edelia vittata Castelnau 1873, were submitted
      for examination because of the presence of black masses in the body wall in the
      abdominal area. The owner reported that approximately 10% of mature fish in one
      dam were affected. The masses had no apparent effect on the health of affected
      fish, but they were unsuitable for sale for aesthetic reasons. After necropsy and
      histological examination, the masses were found to be microsporidial xenomas
      within the abdominal cavity. Transmission electron microscopy results suggest
      that this microsporidian is a previously unreported species, because the
      melanised xenoma wall and internal structure of the spores differ from previously
      described species. The epidemiology of the parasite remains largely unknown and
      highlights the need for further surveys of the disease status and parasites of
      Australian native fish, especially those of interest to aquaculturists.

PMID- 19178482
TI  - Unusual multifocal granulomatous disease caused by actinomycetous bacteria in a
      nestling Derbyan parrot (Psittacula derbiana).
AB  - A nestling Derbyan parrot (Psittacula derbiana) was presented with unusual
      subcutaneous swellings of the thigh regions, and poor growth. Histological
      examination revealed actinomycetous bacteria associated with multifocal systemic
      granulomas. The clinical and pathological findings of the case are presented, and
      some relevant aspects of actinomycetous bacterial infections in mammals and birds
      are discussed. Although granulomatous disease is encountered at times in avian
      species, the actinomycetous bacteria (Nocardia and Actinomyces spp.) have rarely
      been reported in association with multifocal granulomatous disease in birds.

PMID- 19178483
TI  - Uterine adenomyosis in an orang-utan (Pongo abelii/pygmaeus).
AB  - A 48-year-old, multiparous, female hybrid orang-utan (Pongo abelii/pygmaeus) was
      investigated after a 3-year history of irregular and excessively heavy menstrual
      bleeding. Opportunistic pelvic examinations over a 2.5-year period were non
      diagnostic. Medical therapy was not effective. A subtotal hysterectomy with
      bilateral salpingo-ovariectomy was performed. A pedunculated mass spanning 90% of
      the uterine lumen was seen grossly, and histopathology confirmed uterine
      adenomyosis. Adenomyosis is defined as the ectopic occurrence or diffuse
      implantation of endometrial tissue, including glands and stroma, into the
      myometrium. It is common in older, usually premenopausal, multiparous women and
      is frequently associated with other uterine pathology, including endometrial
      hyperplasia and leiomyomas. The most common clinical signs are dysmenorrhoea and
      heavy menstrual bleeding; however, up to 35% of women are asymptomatic. Diagnosis
      is difficult and requires myometrial sampling and an experienced pathologist. A
      hysterectomy in this case was diagnostic and curative. There have been few
      reports of uterine adenomyosis in non-human primates and none reported in an
      orang-utan. Uterine adenomyosis should be considered in the differential
      diagnosis in any multiparous, aged, non-human female primate with irregular and
      excessively heavy menstrual bleeding, and hysterectomy with bilateral salpingo
      ovariectomy is recommended as a diagnostic and therapeutic solution.

PMID- 19178485
TI  - The most common challenges in melanoma diagnosis and how to avoid them.
AB  - Due to its particularly lethal nature and tendency to affect relatively young
      individuals, the timely diagnosis of melanoma remains of paramount importance for
      clinicians and their patients. Unfortunately, melanomas can mimic benign lesions
      that are overwhelmingly more common in the population than are melanomas, and
      misdiagnosis or delay in diagnosis of melanoma can occur. Misdiagnosis of
      melanoma serves as one of the most common causes for malpractice litigation
      brought against medical practitioners. In this review we describe seven clinical
      scenarios that represent challenges in melanoma diagnosis and discuss potential
      strategies for avoiding the errors that commonly give rise to those scenarios.

PMID- 19178487
TI  - PEP005 (ingenol mebutate) gel, a novel agent for the treatment of actinic
      keratosis: results of a randomized, double-blind, vehicle-controlled,
      multicentre, phase IIa study.
AB  - The sap of the plant Euphorbia peplus is a traditional remedy for skin
      conditions, including actinic keratosis. The active constituent of the sap is
      ingenol mebutate (ingenol-3-angelate), formerly known as PEP005. This randomized,
      double-blind, vehicle-controlled, phase IIa study investigated the safety (and
      secondarily the efficacy) of two applications of ingenol mebutate gel in 58
      patients with biopsy-confirmed actinic keratosis. Five preselected lesions were
      treated with ingenol mebutate gel, 0.0025%, 0.01% or 0.05%, or vehicle gel, on
      days 1 and 2 (Arm A) or days 1 and 8 (Arm B). There were no significant
      differences in tolerability or efficacy between Arms A and B. Treatment was well
      tolerated. The most common local skin responses were dose-related erythema,
      flaking/scaling/dryness and scabbing/crusting. Efficacy was greatest with ingenol
      mebutate gel, 0.05%, which resulted in complete clinical clearance of 71% of
      treated lesions (P < 0.0001 vs vehicle gel). In addition, 67% of patients treated
      with ingenol mebutate gel, 0.05% had clinical clearance of at least four of five
      treated lesions (P = 0.0185 vs vehicle gel). Ingenol mebutate gel is being
      developed as a short-course topical therapy for actinic keratosis and non
      melanoma skin cancer.

PMID- 19178488
TI  - Perioperative management and the associated rate of adverse events in
      dermatological procedures performed by dermatologists in New Zealand.
AB  - Dermatological surgery performed in an outpatient setting is common and generally
      perceived as safe, but the potential for serious adverse events does exist.
      Furthermore, there is a current lack of guidelines regarding preoperative and
      intraoperative monitoring of such patients. This is a retrospective study that
      involved a written questionnaire sent to current practising New Zealand
      dermatologists. Aspects investigated include their practice relating to
      preoperative assessments and intraoperative monitoring during standard
      dermatological procedures, and the resulting rate of adverse events. We found
      that most respondents performed dermatological procedures in dedicated theatres
      in outpatient clinics. The majority of survey respondents would screen for and
      optimize risk factors prior to surgery. Most respondents would not record vital
      sign measurements either preoperatively or intraoperatively. Antibiotic
      prophylaxis was generally only prescribed if clinically indicated, and
      anticoagulation and antiplatelet therapies were in the majority of cases never
      withheld prior to surgery. Infection (<3.5%) and bleeding (<2%) were the most
      common postoperative complications, with other serious adverse events being
      extremely rare. Although dermatological surgery continues to be safely performed
      in the outpatient setting, attempts should still be made to identify patients who
      are at higher risk for surgery and extra precautions should be applied to these
      selected patients.

PMID- 19178489
TI  - A novel model of wound healing in the SCID mouse using a cultured human skin
      substitute.
AB  - Studies of skin graft behaviour in rodent excisional wound models are limited by
      the dominance of wound contracture and graft sloughing as primary healing
      responses. To slow skin contraction, polytetrafluoroethylene (Teflon) rings were
      inserted into dorso-lateral full-thickness wounds in SCID mice. Cultured skin
      substitutes (OrCel), composed of cultured human keratinocytes and fibroblasts in
      a bovine collagen sponge, were implanted within the rings. Examination and
      histology of grafts 14 days later showed graft take in four of six recipients,
      with 90% epithelialization and wound contraction of 31-47%. Immunohistochemical
      studies, using human-specific antisera to distinguish graft from host tissues,
      showed that regenerated tissue was predominantly human. Staining with
      anticytokeratin, revealed a multilayered, stratified neoepidermis. HBG were
      identified in keratinocytes in all epidermal layers. Langerhans cells were
      absent. Antihuman vimentin, used as a fibroblast marker, confirmed that cells of
      the neodermis were primarily of human origin. Neoepidermal keratinocytes,
      primarily in the basal and suprabasal layers, were also stained. Results suggest
      that the poly(tetrafluoroethylene) ring inhibited graft sloughing and provided a
      more favourable environment for the skin substitute to regenerate a substantially
      normal human skin.

PMID- 19178490
TI  - Leprosy: not always an easy diagnosis and often a management challenge.
AB  - Leprosy is rare in Australia, particularly in the southern states. We report two
      cases of leprosy in southern Australia that presented to the dermatology
      outpatients' department within a 4-month period. The presentation of the first
      case was complex, making the correct diagnosis difficult. Both cases involved
      immigrants from South-East Asia, were classified as multi-bacillary leprosy as
      defined by the World Health Organization, and were commenced on the recommended
      multiple drug therapy. The ensuing clinical course was complicated, with both
      cases developing Type 1 leprosy reactions. The first case also developed the rare
      but serious dapsone-induced delayed hypersensitivity reaction.

PMID- 19178491
TI  - Management of imatinib-related exacerbation of psoriasis in a patient with a
      gastrointestinal stromal tumour.
AB  - A 62-year-old woman with a pre-existing psoriasis was treated with oral imatinib
      (400 mg/day) for a metastatic gastrointestinal stromal tumour. Within 4 weeks of
      starting therapy, she developed a guttate psoriasis flare. The eruption markedly
      improved within 2 weeks following cessation of imatinib. However, it recurred
      when imatinib was recommenced. She has been able to continue on imatinib (400
      mg/day) with low-dose oral methotrexate (12.5 mg/week) controlling the psoriasis.

PMID- 19178492
TI  - Epidermodysplasia verruciformis-like syndrome in association with systemic lupus
      erythematosus.
AB  - A 43 year-old immunosuppressed woman presented with a widespread macular scaly
      rash, clinically and histologically consistent with epidermodysplasia
      verruciformis. She had no family history of epidermodysplasia verruciformis.
      Human papillomavirus typing was performed on both biopsied skin from clinical
      lesions and on plucked body hairs. The lesional skin from the arm and knee showed
      predominantly human papillomavirus-20 and -47 respectively. Human papillomavirus
      genotyping from the hair follicles revealed that human papillomavirus-20 had the
      highest viral load, irrespective of body site.

PMID- 19178493
TI  - Azathioprine hypersensitivity presenting as a neutrophilic dermatosis in a man
      with ulcerative colitis.
AB  - We report a case of a 46-year-old man with ulcerative colitis being treated with
      oral prednisolone and azathioprine. Two weeks after the initiation of
      azathioprine he presented with fever, fatigue, myalgias and arthralgias and a
      painful cutaneous eruption that was most marked in a sun-exposed distribution.
      This was accompanied by loose, non-bloody diarrhoea. Histopathological assessment
      of a skin biopsy supported a diagnosis of a neutrophilic dermatosis. The
      azathioprine was temporarily withheld and oral prednisolone was increased as it
      was thought that the neutrophilic dermatosis was associated with the underlying
      ulcerative colitis. The patient's symptoms and cutaneous eruption resolved
      quickly and azathioprine was re-introduced. Within 24 h, systemic symptoms
      returned along with a florid recrudescence of his cutaneous eruption. This
      rapidly improved upon withdrawal of azathioprine.

PMID- 19178494
TI  - Leukaemia cutis in a patient treated for breast cancer.
AB  - A 47-year-old woman with a history of breast cancer presented with eruptive
      cutaneous nodules on the trunk and extremities. Treatment for her breast cancer
      had included surgery, radiation and chemotherapy with doxorubicin and
      cyclophosphamide. Biopsy of the skin lesions revealed leukaemia cutis, which led
      to the discovery of acute myelogenous leukaemia. This was felt to be primarily
      induced by doxorubicin. Treatment included induction chemotherapy in preparation
      for a bone marrow transplant, which resulted in the disappearance of the
      cutaneous lesions. However, the patient later succumbed to her leukaemia.

PMID- 19178495
TI  - Treatment of refractory pyoderma gangrenosum with intravenous immunoglobulin.
AB  - We report a patient with pyoderma gangrenosum successfully treated with
      intravenous immunoglobulin. He had previously been treated for 4 years with high
      dose corticosteroids and had developed insulin-dependent diabetes mellitus.
      Multiple corticosteroid-sparing agents had failed or were contraindicated. He
      developed no adverse effects from intravenous immunoglobulin, which allowed
      reduction of his prednisone to 3 mg/day, and his ulcer has completely healed.

PMID- 19178496
TI  - Giant basal cell carcinoma masquerading as an osteogenic sarcoma.
AB  - An 88-year-old man presented to the dermatology outpatient clinic with an 11
      month history of a rapidly growing mass overlying a clavicular fracture site. The
      lesion was 8 x 6 cm, painful, fixed to deeper structures and ulcerated.
      Superficial and deep biopsies yielded invasive basal cell carcinoma. Imaging
      demonstrated extensive soft tissue invasion into muscle, bone and potentially
      into the lung parenchyma. Due to complications arising from subsequent diagnostic
      procedures, the patient declined further invasive tests. The cutaneous lesion was
      treated with palliative radiotherapy. We explore the literature regarding the
      tumorigenic effects of peri-fracture cytokines on the biological behaviour of
      basal cell neoplasms.

PMID- 19178497
TI  - Primary cutaneous angioplasmocellular hyperplasia.
AB  - Primary cutaneous angioplasmocellular hyperplasia is a plasma-cellular infiltrate
      that has been reported only once previously in the literature, in a report of a
      case affecting two Latin American patients. In the present case, a systemically
      well 62-year-old Caucasian man presented with a nodule on the back of the neck.
      Histology showed a vascular proliferative process with an abundance of plasma
      cells in the stroma. There has been no recurrence of the lesion 2 years following
      curettage and diathermy. The clinicopathological presentation is consistent with
      primary cutaneous angioplasmocellular hyperplasia.

PMID- 19178498
TI  - A pink papule.

PMID- 19178500
TI  - Acquired dermal melanocytosis involving the hand.

PMID- 19178506
TI  - GH treatment reduces total ghrelin in Prader-Willi syndrome (PWS) and may
      confound ghrelin studies in young PWS children.

PMID- 19178507
TI  - Association of plasma visfatin levels with inflammation, atherosclerosis and
      acute coronary syndromes (ACS) in humans.
AB  - OBJECTIVES: Visfatin is a new cytokine that act as an insulin analogue on the
      insulin receptor and may link obesity and insulin resistance. It was recently
      shown that visfatin plays a role in plaque destabilization. However, the role of
      visfatin in atherosclerosis remains to be elucidated. We sought to assess whether
      plasma visfatin level is independently associated with inflammation,
      atherosclerosis and acute coronary syndromes (ACS). DESIGN AND PATIENTS: Two
      hundred and fifty-three patients undergoing coronary angiography were divided
      into three subgroups: chronic coronary artery disease (CAD) (n = 102), ACS (n =
      100) and control patients (n = 51). The plasma samples were thawed and analysed
      for circulating visfatin, monocyte chemoattractant protein 1 (MCP-1), interleukin
      6 (IL-6), high sensitivity C-reactive protein (hs-CRP). The association of
      visfatin with risk factors, inflammation, atherosclerosis, and ACS was
      determined. RESULTS: Plasma visfatin levels were significantly higher in chronic
      CAD and ACS compared with control patients. Multiple regression analysis
      demonstrated that plasma visfatin levels correlated with inflammatory factors and
      were associated with chronic CAD (odds ratio [OR][95% confidence interval], for
      second, third and fourth quartiles were 1.74 [0.96-2.69], 1.54 [0.85-2.28] and
      1.84 [0.98-2.87], respectively) and ACS (ORs for second, third and fourth
      quartiles were 2.56 [1.57-3.34], 4.61 [1.94-10.96] and 6.52 [2.34-18.12],
      respectively) following adjustment for established risk factors and other
      inflammatory factors. CONCLUSIONS: Plasma visfatin levels are significantly
      associated with CAD, particularly ACS, independent of well-known CAD risk
      factors.

PMID- 19178508
TI  - Relationship between body composition and bone mineral density (BMD) in
      perimenopausal Korean women.
AB  - OBJECTIVES: Osteoporosis is a disease that increases the fracture rates and it is
      the major cause of increased mortality and morbidity in the elderly people. To
      determine which component of body composition is most important to bone health,
      we analysed the relationship between elements of the body composition and bone
      mineral density (BMD) in Korean women. DESIGN: Cross-sectional clinical study.
      PATIENTS: Totally 1694 women (mean age 51 years) were selected from subjects who
      participated in a medical check-up program. MEASUREMENTS: Body composition
      analysis was performed by segmental bioelectric impedance method and lean mass,
      fat mass and per cent body fat measured. Waist: hip ratio (WHR) was assessed as a
      marker for visceral fat. Lumbar spine (L-spine) BMD was measured by dual X-ray
      absorptiometry (DEXA). As menopausal status could not be confirmed in all
      subjects, we divided the subjects into two groups according to the age > 50 years
      and < 50 years. RESULTS: Among the entire population, 599 subjects (35.4%) were
      osteopaenic and 229 subjects (13.5%) were osteoporotic. The bivariate correlation
      among the variables showed that weight had the highest correlation with fat mass.
      Mean lean mass was decreased and the WHR increased as the subjects progressed
      from normal to osteoporotic status; fat mass was the highest among the
      osteopaenic subjects. L-spine BMD showed a positive correlation with lean mass,
      and a negative correlation with WHR by bivariate correlation analysis. However,
      fat mass had a negative correlation with L-spine BMD only after adjustment for
      age and weight. Multiple regression analysis with L-spine BMD as the dependent
      variable showed that age, height, fasting insulin, lean mass and WHR were
      significant determinants of the L-spine BMD (R(2) = 0.170, P < 0.05). CONCLUSION:
      In this Korean female population, L-spine BMD showed a consistently positive
      correlation with lean mass and a negative correlation with WHR. Fat mass failed
      to show any consistent correlation with L-spine BMD in this study population.

PMID- 19178509
TI  - Effects of peripheral administration of synthetic human glucose-dependent
      insulinotropic peptide (GIP) on energy expenditure and subjective appetite
      sensations in healthy normal weight subjects and obese patients with type 2
      diabetes.
AB  - BACKGROUND: Apart from their role in insulin secretion and glucose homeostasis,
      the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic peptide (GIP) exert a number of extra-pancreatic effects which in
      the case of GIP remain largely unknown. DESIGN/PATIENTS: Six obese male patients
      with diet-controlled type 2 diabetes (T2DM) and six healthy lean male subjects
      were studied. The protocol included four experiments for each participant that
      were carried out in randomized order and included: GLP-1 infusion at a rate of 1
      pmol/kg/min for 4 h, GIP at a rate of 2 pmol/kg/min, GLP-1 (at 1 pmol/kg/min)
      with GIP (at 2 pmol/kg/min), and placebo infusion for 4 h. Energy expenditure
      (EE) was measured throughout with indirect calorimetry and subjects were given a
      series of visual analogue scales to rate hourly their hunger, fullness, urge to
      eat and prospective consumption of food. Immediately following termination of the
      infusions all subjects were offered a free choice buffet lunch and total calorie
      and macronutrient intake was calculated. RESULTS: During GIP infusion there was a
      trend for healthy subjects to report higher hunger scores and a reduction in EE
      only when compared with placebo. These parameters remained unchanged in patients
      with T2DM. Ad libitum energy intake after all four infusions was the same in both
      groups. CONCLUSION: We report here for the first time that GIP infusion may
      impact on resting EE and subjective appetite sensations in normal weight healthy
      subjects and further studies with larger numbers of subjects are required to help
      define more conclusively the precise role of GIP in energy balance in humans.

PMID- 19178510
TI  - Vitamin D insufficiency--a novel mechanism of statin-induced myalgia?

PMID- 19178511
TI  - Impact of thyroid function and polymorphisms in the type 2 deiodinase on blood
      pressure: the Rotterdam Study and the Rotterdam Scan Study.
AB  - INTRODUCTION: Thyroid function and genetic variation in the hypothalamus
      pituitary-thyroid axis have been implicated in blood pressure regulation and
      susceptibility to hypertension. However studies conducted thus far were small
      with controversial results. OBJECTIVE: To examine whether serum thyroid
      parameters and polymorphisms in the type 2 deiodinase and the TSH receptor are
      associated with blood pressure and the presence of hypertension in two large
      cohorts of elderly subjects. DESIGN AND PARTICIPANTS: We studied a random sample
      of 1444 subjects of the Rotterdam study, and 997 subjects of the Rotterdam Scan
      study, two population-based cohort studies among elderly individuals aged 55-90
      years. Outcome measurements Data on blood pressure and hypertension were
      obtained, and serum thyroid parameters, D2-Thr92Ala, D2-ORFa-Gly3Asp and TSHR
      Asp727Glu polymorphisms were determined. RESULTS: In contrast to previous
      findings, no consistent and/or significant associations were found between serum
      TSH and FT4 and blood pressure in both cohorts. In addition, the D2-Thr92Ala, D2
      ORFa-Gly3Asp and TSHR-Asp727Glu polymorphisms were not associated with blood
      pressure or the risk of hypertension. CONCLUSIONS: In two large populations of
      elderly subjects, neither serum thyroid parameters nor polymorphisms in the type
      2 deiodinase and the TSH receptor, were associated with blood pressure or the
      presence of hypertension. Our data suggest that thyroid function is not an
      important determinant of hypertension in elderly Dutch subjects.

PMID- 19178512
TI  - Risk factors for cardiovascular disease do not fully explain differences in
      carotid intima-media thickness between Indigenous and European Australians
      without diabetes.
AB  - OBJECTIVE: To investigate whether cardiovascular risk factors can explain the
      higher carotid intima-media thickness (CIMT) in Indigenous compared with European
      Australians. DESIGN: Cross-sectional study in three subgroups. PATIENTS: Non
      diabetic urban European (n = 86), urban Indigenous (n = 69), and remote
      Indigenous (n = 60) Australians aged 25-64 years. MEASUREMENTS: CIMT, age, sex,
      anthropometry, blood pressure, smoking status, fasting glucose and insulin,
      haemoglobin (Hb)A1c, homocysteine, C-reactive protein (CRP), lipids, urinary
      albumin and creatinine. RESULTS: CIMT and levels of risk factors, except fasting
      glucose and total cholesterol, worsened across the three groups. Log(n) fasting
      insulin [beta = 0.022, 95% confidence interval (CI) 0-0.0439], age (beta = 0.006,
      95% CI 0.004-0.007), gender (female beta = -0.005 vs. male, 95% CI -0.084 to 
      0.026), mean arterial pressure (MAP) (beta = 0.001, 95% CI 0.001-0.002) and
      ethnicity/location [urban Indigenous (beta = 0.027, 95% CI -0.010 to 0.064 vs.
      European); remote Indigenous (beta = 0.083, 95% CI 0.042-0.123 vs. European)]
      explained 41% of variance in CIMT. Significant interactions were seen for
      ethnicity/location with age (P = 0.014) and MAP (P = 0.018). Age was consistently
      associated with CIMT across the three populations, and was associated with larger
      increments in CIMT for the Indigenous subgroups (beta = 0.007, 95% CI 0.005-0.009
      urban; beta = 0.007, 95% CI 0.004-0.010 remote) compared with Europeans (beta =
      0.003, 95% CI 0.002-0.006) in models including age, sex and MAP. MAP was only
      associated with CIMT in the remote Indigenous subgroup. CONCLUSION: After
      adjusting for selected risk factors, CIMT in remote Indigenous participants was
      still higher than in Europeans. The slope of the association between age and CIMT
      steepened from urban Europeans to remote Indigenous.

PMID- 19178513
TI  - Cerebral white matter hyperintensity is mainly associated with hypertension among
      the components of metabolic syndrome in Koreans.
AB  - BACKGROUND: Cerebral white matter hyperintensity (WMH) is a common abnormality in
      brain magnetic resonance imaging (MRI) and is known to be associated with
      ischaemic stroke. Previous studies revealed that the risk factors for cerebral
      WMH were age, female gender, hypertension and diabetes. In this study we examined
      the association between cerebral WMH and metabolic syndrome, a cluster of
      hypertension, glucose intolerance, abdominal obesity and dyslipidaemia. METHODS
      AND RESULTS: We reviewed the results of brain MRI of 5498 subjects who underwent
      routine check-ups including laboratory tests at the Seoul National University
      Health Care System. Among the subjects who met the inclusion criteria (n = 5104),
      1693 (33.2%) had cerebral WMH. They were characterized by old age, female
      predominance, higher body mass index (BMI), larger waist circumference, higher
      blood pressure, higher fasting plasma glucose level, and higher haemoglobin A1c
      (HbA1c). In multivariate analyses, age, female gender and hypertension were the
      independent risk factors for cerebral WMH. Metabolic syndrome was associated with
      cerebral WMH after adjusting for age and gender [odds ratio (OR) 1.20, 95%
      confidence interval (CI) 1.04-1.39, P = 0.014]. Among the components of metabolic
      syndrome, hypertension was independently associated with cerebral WMH (OR 1.20,
      95% CI 1.05-1.38, P = 0.007). CONCLUSION: Age, female gender and hypertension
      were risk factors for cerebral WMH in the Korean population. Cerebral WMH was
      also associated with metabolic syndrome; however, metabolic syndrome offered no
      advantage over hypertension alone in predicting cerebral WMH.

PMID- 19178514
TI  - Tissue mRNA expression of the glucocorticoid receptor and its splice variants in
      fatal critical illness.
AB  - BACKGROUND: Critical illness results in activation of the hypothalamic-pituitary
      adrenal (HPA) axis, which might be accompanied by a peripheral adaptation in
      glucocorticoid sensitivity. Tissue sensitivity is determined by the active
      glucocorticoid receptor GRalpha, of which two splice variants involving the
      hormone-binding domain exist, GRbeta and GR-P. OBJECTIVE: To study tissue mRNA
      expression of the GR and its splice variants in fatal critical illness. DESIGN
      AND METHODS: We assessed mRNA expression of the GRalpha, GRbeta and GR-P variants
      in liver (n = 58) and muscle (n = 65) of patients who had died after intensive
      care, and had been randomized for insulin treatment. We analysed whether GR mRNA
      expression was associated with insulin treatment, cortisol levels and
      glucocorticoid treatment. RESULTS: GRalpha and GR-P mRNA constituted 87 +/- 8%
      and 13 +/- 2%, respectively, of total GR mRNA in liver. GRbeta mRNA could only be
      amplified in five liver samples. All variants were present in most muscle samples
      (alpha = 96 +/- 11%, P = 3.9 +/- 0.4%, beta = 0.010 +/- 0.002%). GR expression
      was not associated with insulin therapy. A strong positive relationship was
      observed between the different GR variants in both liver and muscle (P < 0.001
      for all). Serum cortisol levels were negatively associated with liver GRalpha and
      muscle GR-P expression (P < 0.05). mRNA expression of both liver GRalpha and GR
      P, but not muscle GR, was substantially lower in patients who had received
      exogenous glucocorticoids (P < 0.01). CONCLUSION: We demonstrate the presence of
      GRalpha and GR-P mRNA in liver and of GRalpha, GRbeta and GR-P mRNA in muscle,
      with no evidence for altered splicing in critical illness. In contrast to muscle
      GR, liver GR expression was substantially lower in patients receiving exogenous
      glucocorticoids.

PMID- 19178515
TI  - Breastfeeding and maternal and infant iodine nutrition.
AB  - OBJECTIVE: The aim of this review is to explore information available regarding
      iodine secretion in milk, both mothers and infants iodine nutrition during
      breastfeeding and to make recommendations for appropriate iodine supplementation
      during lactation. DESIGN: MEDLINE was queried for studies between 1960 and 2007
      that included lactation and breastfeeding with iodine and iodine deficiency.
      Studies were selected if they studied (i) Secretion of iodine in breast milk;
      (ii) breastfeeding and iodine nutrition; (iii) factors affecting maternal iodine
      metabolism and (iv) recommendations for iodine supplementation during
      breastfeeding. RESULTS: Thirty-six articles met the selection criteria. The
      iodine content of breast milk varies with dietary iodine intake, being lowest in
      areas of iodine deficiency with high prevalence of goitre. Milk iodine levels are
      correspondingly higher when programs of iodine prophylaxis such as salt
      iodization or administration of iodized oil have been introduced. The small
      iodine pool of the neonatal thyroid turns over very rapidly and is highly
      sensitive to variations in dietary iodine intake. Expression of the sodium iodide
      symporter is up-regulated in the lactating mammary gland which results in
      preferential uptake of iodide. In areas of iodine sufficiency breast milk iodine
      concentration should be in the range of 100-150 microg/dl. Studies from France,
      Germany, Belgium, Sweden, Spain, Italy, Denmark, Thailand and Zaire have shown
      breast milk concentrations of < 100 microg/l. Adequate levels of iodine in breast
      milk have been reported from Iran, China, USA and some parts of Europe.
      CONCLUSIONS: Adequate concentration of iodine in breast milk is essential to
      provide for optimal neonatal thyroid hormone stores and to prevent impaired
      neurological development in breast-fed neonates. In many countries of the world,
      low iodine content of the breast milk indicates less than optimum maternal and
      infant iodine nutrition. The current WHO/ICCIDD/UNICEF recommendation for daily
      iodine intake (250 microg for lactating mothers) has been selected to ensure that
      iodine deficiency dose not occur in the postpartum period and that the iodine
      content of the milk is sufficient for the infant's iodine requirement.

PMID- 19178517
TI  - Initial growth deceleration during GnRH analogue therapy for precocious puberty.
AB  - OBJECTIVES: To compare the efficacy of goserelin and leuprolide on initial
      deceleration of growth and weight gain during the first 12 months of GnRH
      analogue treatment for precocious puberty. DESIGN: Retrospective cohort analysis.
      PATIENTS: Forty children with precocious puberty treated with either goserelin or
      leuprolide (33 females, mean age 7.3 and 7.7 years, respectively, at the start of
      treatment). MEASUREMENTS: The primary outcomes were baseline-to-6-months and 6
      months-to-12-months change in height standard deviation score (SDS) and body mass
      index (BMI). Relative tall stature was calculated as the difference between
      height SDS and mid-parental height (MPH) SDS at baseline. RESULTS: Goserelin and
      leuprolide were associated with similar suppression of serum LH during the first
      12 months of treatment (P = 0.62). Greater relative tall stature was strongly
      associated with more advanced bone age, greater BMI SDS and with greater
      reduction in height SDS in the first 6 months. Adjusted for relative tall
      stature, goserelin therapy was associated with significantly greater suppression
      of growth than leuprolide (P = 0.025) in the first 6 months of treatment, with no
      subsequent change in the second 6 months. A similar, significant increase in BMI
      was seen with both analogues. CONCLUSIONS: Both GnRH analogues were associated
      with effective biochemical suppression of puberty; however, goserelin was more
      effective at reducing linear growth during the first 6 months. Relative tall
      stature was a major determinant of the initial response to treatment.

PMID- 19178516
TI  - Octreotide LAR vs. surgery in newly diagnosed patients with acromegaly: a
      randomized, open-label, multicentre study.
AB  - OBJECTIVE: This prospective randomized study evaluated the efficacy and safety of
      octreotide LAR vs. surgery in newly diagnosed acromegalic patients. METHODS:
      Totally 104 male and female patients were enrolled in a 50-week, exploratory,
      open-label and randomized study. Eligible patients were randomized to receive
      either octreotide LAR 20 mg every 28 days or to undergo surgery. Efficacy was
      assessed by changes in mean GH and IGF-I serum concentrations, at weeks 12, 24
      and 48. Tumour volume was assessed by contrast-enhanced MRI. In both groups,
      treatment adjustment was performed for patients uncontrolled at week 12 or 24.
      Octreotide LAR patients received a dose increased to 30 mg or, if already
      receiving this dose, investigator and patients could decide to cross-over to
      surgery. Patients uncontrolled after surgery received octreotide LAR 20 mg,
      increased to 30 mg if acromegaly was still uncontrolled. RESULTS: Overall success
      rates at weeks 24 and 48 were 25% and 28% for the octreotide LAR group and 49%
      and 39% for the surgery group. Only the difference observed at week 24 was
      statistically significant (P = 0.047). Both groups had a significant (> 20%)
      tumour shrinkage: 73% of patients in the octreotide LAR group and 95% in the
      surgery group. Major differences between octreotide LAR and surgery group in the
      occurrence of adverse events were gastrointestinal (71%vs. 27%), hepatobiliary
      (41%vs. 8%) and respiratory (5%vs. 28%). CONCLUSION: This first randomized study
      in unselected patients indicates that the 48-week treatment outcome of octreotide
      LAR as first-line treatment of acromegaly does not significantly differ from
      surgery. As a complete response to surgery in GH-secreting macro-adenomas can be
      difficult, first-line therapy with octreotide LAR can be considered as a viable
      alternative for most patients with acromegaly, due to its low complication rate.

PMID- 19178518
TI  - Novel mutation in the adiponectin (ADIPOQ) gene is associated with
      hypoadiponectinaemia in Japanese-Brazilians.
AB  - OBJECTIVE: Adiponectin is an important mediator of insulin sensitivity, encoded
      by the ADIPOQ gene. Here we describe two Japanese-Brazilian families with
      hypoadiponectinaemia due to a novel mutation in ADIPOQ. DESIGN AND PATIENTS: In
      this study, we examined the entire translated regions of adiponectin in Japanese
      Brazilians, a population with one of the highest prevalence rates of diabetes
      worldwide. We screened 200 patients with type 2 diabetes (DM) and 240 age-matched
      subjects with normal glucose tolerance. RESULTS: A novel heterozygous T deletion
      at position 186 in exon 2 of ADIPOQ, causing a frameshift at codon 62 and leading
      to a premature termination at codon 168 (p.Gly63ValfsX106), was found in two
      individuals with diabetes. This mutation was not found in 240 nondiabetic control
      subjects. In addition, we screened the mutation in an expanded set of 100
      nondiabetic subjects from the general Brazilian population, but we found no
      mutations. In addition, six family members of the probands were identified as
      mutation-carriers. Individuals who were mutation-carriers had markedly low plasma
      adiponectin concentrations compared with those without the mutation [DM: 0.65
      (0.59-1.34) microg/ml vs. 5.30 (3.10-8.55) microg/ml, P < 0.0001; normal glucose
      tolerance: 0.95 (0.76-1.48) microg/ml vs. 8.50 (5.52-14.55) microg/ml, P =
      0.003]. All individuals carrying the p.Gly63ValfsX106 mutation and older than 30
      years were found to be diabetic. CONCLUSIONS: We describe for the first time a
      frameshift mutation in exon 2 of the ADIPOQ gene, which modulates adiponectin
      levels and may contribute to the genetic risk of late-onset diabetes in Japanese
      Brazilians.

PMID- 19178519
TI  - Reduced levels of GH during GnRH analogue treatment in pubertal short girls born
      small for gestational age (SGA).
AB  - CONTEXT: Several studies showed a decrease in height velocity during GnRH
      analogue (GnRHa) treatment. No information is available on GH levels during GnRHa
      treatment in short SGA girls. OBJECTIVE: To study overnight GH profiles and IGF-I
      and IGFBP-3 levels in girls with Tanner stage 2 and stage 3, before and after 3
      months of GnRHa treatment, and to compare levels with those found in prepubertal
      short SGA girls. PATIENTS: Twenty-four pubertal and 16 prepubertal short SGA
      girls. INTERVENTION: After baseline overnight GH profiles, pubertal girls
      received leuprorelide acetate depots of 3.75 mg subcutaneously every 4 weeks.
      OUTCOME MEASURES: GH, IGF-I and IGFBP-3 levels. RESULTS: At baseline, GH levels
      were comparable to levels found in prepubertal short SGA girls and IGF-I and
      IGFBP-3 SDS were significantly below the population mean. After 3 months of GnRHa
      treatment, AUC(0) (P = 0.02), mean (P = 0.02) and maximum GH levels (P = 0.008)
      had significantly decreased. Mean GH levels were significantly lower than in
      prepubertal short SGA girls (P = 0.03). Eight girls with more than 40% decrease
      in mean GH levels also had a significantly greater decrease in IGF-I and IGFBP-3
      levels. Mean and maximum GH levels at baseline correlated significantly with
      those after 3 months of GnRHa treatment. CONCLUSION: Short SGA girls lack the
      normal increase in GH levels seen in puberty and have reduced IGF-I and IGFBP-3
      levels, which might explain their reduced pubertal growth spurt. GnRHa treatment
      led to a significant reduction in GH levels. Therefore, combining GnRHa treatment
      with GH treatment might improve adult height of short SGA girls.

PMID- 19178520
TI  - Intron polymorphism in the KIAA0350 gene is reproducibly associated with
      susceptibility to type 1 diabetes (T1D) in the Han Chinese population.
AB  - OBJECTIVE: Three independent genome-wide association studies in white populations
      have reported that single nucleotide polymorphisms (SNPs) in the KIAA0350 gene
      are associated with susceptibility to type 1 diabetes (T1D). The gene product of
      KIAA0350 is predicted to be a sugar binding C-type lectin. In the present study,
      we investigated whether SNPs in this gene were associated with T1D in the Han
      Chinese population. DESIGN AND METHODS: In this case-controlled association
      study, a total of 205 T1D patients and 422 non-diabetic subjects of the Han
      Chinese population were enrolled. Two SNPs, namely, rs17802927 and rs725613, in
      the KIAA0350 gene were genotyped using a polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) protocol. RESULTS: The intron SNP
      rs725613 was strongly associated with T1D in the Han Chinese population [P =
      0.00007, odds ratio (OR) = 0.527, 95% confidence interval (CI) = 0.383-0.726],
      and the frequencies of its genotypes in the T1D group significantly differed from
      those in the control group (P = 0.0001). CONCLUSION: The intron polymorphism
      rs725613 in the KIAA0350 gene is associated with susceptibility to T1D, and this
      association is not race specific.

PMID- 19178521
TI  - Relationship of low-density lipoprotein (LDL) particle size to thyroid function
      status in Koreans.
AB  - OBJECTIVE: Dyslipidaemia is a well-known manifestation of thyroid dysfunction.
      Recently, small low-density lipoprotein (LDL) particle size has been linked with
      development of cardiovascular disease. To better understand the effects of
      thyroid dysfunction on the development of cardiovascular disease, we examined LDL
      particle size and lipid profiles in subjects with different thyroid function.
      METHODS: Included were 46 patients with overt hypothyroidism, 57 patients with
      subclinical hypothyroidism, 46 patients with overt hyperthyroidism, 51 patients
      with subclinical hyperthyroidism, and 110 age- and sex-matched healthy control
      subjects. We measured LDL particle size and lipid profiles in these subjects.
      RESULTS: No significant differences were found in LDL particle size between the
      groups with different thyroid function. Serum total cholesterol and LDL
      cholesterol levels were significantly higher in the cases of hypothyroidism than
      in the cases of hyperthyroidism and the healthy control subjects. Serum
      triglyceride levels were higher in subjects with overt hypothyroidism than in
      those with overt hyperthyroidism or healthy control subjects. CONCLUSIONS: LDL
      particle size, the emerging risk factor for atherosclerosis, did not appear to be
      significantly affected by the degree of thyroid dysfunction. Increased risk of
      atherosclerosis in hypothyroidism does not appear to be associated with LDL
      particle size, the non-traditional cardiovascular risk factor.

PMID- 19178522
TI  - Ultrasound of peripheral nerves in acromegaly: changes at 1-year follow-up.
AB  - CONTEXT: We have previously demonstrated peripheral nerve enlargement in
      acromegaly. OBJECTIVE: The aim of this study was to use ultrasound (US) to assess
      any changes in the peripheral nerves of patients with acromegaly 1 year after the
      first evaluation. PATIENTS: We prospectively examined the median and ulnar nerve
      cross-sectional area (CSA) in 34 non-diabetic, patients with acromegaly (18
      females and 16 males; 18-79 years) and 34 age-, sex-, BMI-matched controls, using
      a 17-5 MHz US probe. INTERVENTION: The median nerve was examined at the mid
      forearm (MN-f) and at the carpal tunnel (MN-Ct) levels; the ulnar nerve at mid
      forearm (UN-f) and at distal arm (UN-a). Patients were grouped according to the
      clinical control of the disease: 'improved'; 'always controlled'; 'always
      uncontrolled'; and 'worsened'. RESULTS: The median nerve at mid-forearm (MN-f),
      the ulnar nerve at mid-forearm (UN-f) and at distal arm (UN-a) were significantly
      reduced after 1-year follow-up in all patients (P < 0.001, P < 0.008, P < 0.012,
      respectively). In the 'improved' group, there was a significant reduction of
      median nerve CSA examined at mid-forearm (MN-f) (P = 0.02), and distal arm ulnar
      nerve CSA (UN-a) (P = 0.002). In the other groups no statistically significant
      differences in ultrasound parameters were recorded. However, UN-a, UN-f, MN-f, MN
      ct were still significantly higher in all groups compared with controls (P <
      0.001). CONCLUSION: These data demonstrate that median and ulnar nerves CSA are
      reduced after 1 year follow-up, in line with the reduction of GH/IGF-I levels.
      However, as the control of the disease incompletely reverts nerve enlargement,
      this phenomenon could be only partially reversible.

PMID- 19178523
TI  - Transition process of patients with type 1 diabetes (T1DM) from paediatric to the
      adult health care service: a hospital-based approach.
AB  - INTRODUCTION: The outcomes of different types of transitions of young people with
      chronic diseases have been poorly investigated. OBJECTIVE: To evaluate and
      compare a structured transition from the paediatric diabetes services (PDS) into
      the adult diabetic services (ADS) with an unstructured one. DESIGN: We
      retrospectively investigated 62 adolescents and young adults with type 1 diabetes
      discharged from the PDS from 1 January 1994 to 31 December 2004. Thirty-two
      patients (group A) were transferred to the ADS of the same hospital with an
      unstructured method (letter) and 30 patients after a structured transfer planned
      with adult physicians (group B). We analysed the date of the first admission in
      ADS, the glycated haemoglobin (HbA1c), the clinic attendance rate in PDS and in
      the first year in ADS, and a phone questionnaire on the transition experience.
      RESULTS: The duration of the transfer was longer in A than in B with a lack of
      medical assistance during the unstructured transition (P < 0.001). At the first
      visit in ADS, before any medical intervention, HbA1c was improved in B compared
      to the last in PDS (P < 0.01), and had a trend in worsening in A. After 1 year in
      the ADS there was a better clinical attendance, and a lower HbA1c in B than in A
      (P < 0.05). All the subjects of group B reported a favourable opinion for the
      structured transition (P < 0.0001). CONCLUSION: The transition process plays an
      important role in diabetic care and a structured plan is mandatory to avoid to
      lose the patients and to get worse their health.

PMID- 19178524
TI  - Factors determining inadequate hypoglycaemia during insulin tolerance testing
      (ITT) after pituitary surgery.
AB  - BACKGROUND: Some patients fail to achieve adequate hypoglycaemia following a
      standard dose of intravenous insulin during the insulin tolerance test (ITT).
      Persistent acromegaly or Cushing's disease may contribute to inadequate
      hypoglycaemia. Aim To identify factors that predict failure to achieve adequate
      hypoglycaemia during an ITT after pituitary surgery. METHODS: We reviewed
      consecutive ITTs performed over a 10-year period in 76 patients following
      pituitary surgery. Analyses were performed to determine if body mass index (BMI),
      fasting blood glucose (FBG), cortisol, GH status or underlying diagnosis
      influenced the outcome. RESULTS: Adequate hypoglycaemia (blood glucose < 2.2
      mmol/l) was not achieved in 33 patients (Group 1) following a standard dose of
      neutral insulin (0.1 units/kg); 43 patients (Group 2) achieved adequate
      hypoglycaemia. Group 1 had significantly higher BMI, FBG, baseline cortisol and
      peak cortisol concentrations than Group 2. Peak GH response was not different.
      Multiple regression analysis showed that FBG was the only independent predictor
      of adequate hypoglycaemia. An insulin dose of 0.2 units/kg achieved adequate
      hypoglycaemia in 80% of patients with FBG >or= 5.5 mmol/l. In patients with
      acromegaly or Cushing's disease, failure to achieve adequate hypoglycaemia was
      associated with persistent disease. CONCLUSION: FBG is an important determinant
      of the dose of insulin required to achieve adequate hypoglycaemia during an ITT
      in patients after pituitary surgery. A standard insulin dose of 0.1 U/kg is
      insufficient for adequate hypoglycaemia in patients with FBG > 5.5 mmol/l.
      Adequate response to a standard dose of insulin suggests a likelihood of cure of
      acromegaly or Cushing's disease after pituitary surgery.

PMID- 19178525
TI  - PPARgamma Pro12Ala Pro/Pro and resistin SNP-420 G/G genotypes are synergistically
      associated with plasma resistin in the Japanese general population.
AB  - OBJECTIVE: The Ala allele of the Pro12Ala polymorphism (rs1801282) of peroxisome
      proliferator-activated receptor gamma (PPARgamma) is protective against type 2
      diabetes (T2DM). Resistin, secreted from adipocytes, causes insulin resistance in
      rodents. Resistin gene expression is reduced by the PPARgamma ligand. We
      previously reported that subjects with the G/G genotype of a resistin gene single
      nucleotide polymorphism (SNP) at -420 (rs1862513) had the highest circulating
      resistin levels, followed by C/G and C/C. The aim of this study was to determine
      the relationship among PPARgamma Pro12Ala polymorphism, resistin SNP-420, and
      plasma resistin. DESIGN, PATIENTS AND MEASUREMENTS: We cross-sectionally analysed
      2077 community-dwelling subjects attending an annual medical check-up. Genotypes
      were determined by TaqMan analysis. Fasting plasma resistin was measured using
      ELISA. RESULTS: Plasma resistin appeared to be higher in subjects with the
      Pro/Pro genotype of PPARgamma than those with Pro/Ala and Ala/Ala genotypes (mean
      +/- SE, 11.6 +/- 0.2 vs. 10.4 +/- 0.5 microg/l). Multiple regression analysis,
      adjusted for age, gender, BMI, and resistin SNP-420, revealed that the Pro/Pro
      genotype was a positive predictor of plasma resistin (PPARgamma , Pro/Pro vs.
      Pro/Ala + Ala/Ala, unstandardized regression coefficient (beta) = 1.03, P =
      0.0384). The effects of the Pro/Pro genotype of PPARgamma (Pro/Pro vs. Pro/Ala +
      Ala/Ala) and the G/G genotype of resistin SNP-420 (G/G vs. C/C) on plasma
      resistin were synergistic (beta = 4.76, P = 0.011). CONCLUSIONS: The PPARgamma
      Pro12Ala Pro/Pro and resistin SNP-420 G/G genotypes were synergistically
      associated with plasma resistin, when adjusted for age, gender, and BMI, in the
      Japanese general population.

PMID- 19178526
TI  - Neurocognitive consequences of surgery and radiotherapy for tumours of the
      pituitary.
AB  - The management of patients with pituitary tumours requires a multidisciplinary
      approach utilizing a number of different treatment modalities that can impact
      upon pituitary function and may disrupt important areas of cerebral tissue that
      are important for normal neurocognitive function. Patients frequently report
      problems with memory and sustained attention that impact upon normal day-to-day
      life. At present it is unclear whether any causal link exists between treatments
      for pituitary tumours and abnormalities of memory and higher mental function. The
      domains of function affected in patients with pituitary tumours are memory and
      executive functions, which are involved in the control and direction of lower
      level, more automatic functions such as attention and motor skills. The evidence
      for disruption in these modalities is stronger for memory than for executive
      function. This may be due to variability in study design, insufficient tests and
      the potential inclusion of fundamentally different tumour types. The purpose of
      this review is to examine the available evidence to determine whether pituitary
      disease, its management, or subsequent complications are responsible for any
      neuropsychological deficits in pituitary patients. Furthermore we address
      methodological issues that may account for the apparent disparate neurocognitive
      data that exist in this patient group.

PMID- 19178527
TI  - Demographic, physical and lifestyle factors associated with androgen status: the
      Florey Adelaide Male Ageing Study (FAMAS).
AB  - OBJECTIVE: Plasma androgen levels are inversely associated with health in men,
      the age-related decline of which may result from factors other than ageing per
      se. This study aimed to determine the effects of demographic, physical and
      lifestyle factors on age-related androgen status in men. DESIGN: An observational
      survey of a regionally representative male population residing in the North West
      regions of Adelaide, Australia. PARTICIPANTS: Study sample includes 1195 men aged
      35-81 years with a response rate of 45.1%. MEASUREMENTS: Plasma levels of total
      testosterone (TT), bioavailable testosterone (BT), SHBG, insulin-like peptide 3
      (INSL3), and gonadotrophins were measured along with an extensive list of
      demographic, physical and lifestyle factors including body composition, muscle
      strength and biomarkers of chronic diseases, physical activity, nutrition and
      smoking behaviour. RESULTS: Low TT was mostly associated with high abdominal fat
      and triglycerides and low muscle strength rather than ageing per se. Low BT was
      associated with increased age followed by high whole body fat percentage. BT and
      TT levels were higher in unmarried men and smokers. SHBG levels increased with
      age, but were also inversely associated with insulin and triglycerides. The
      Leydig cell specific factor INSL3 was the strongest biomarker associated with
      both TT and BT. CONCLUSIONS: Factors associated with low androgen status variably
      include high body fat percentage, low muscle strength and biomarkers of the
      metabolic syndrome. Reducing exposure to factors that adversely affect androgen
      status may improve the general health of ageing men by mechanisms yet to be
      defined.

PMID- 19178528
TI  - Comparison of the molecular consequences of different mutations at residue 754
      and 690 of the androgen receptor (AR) and androgen insensitivity syndrome (AIS)
      phenotype.
AB  - OBJECTIVE: Androgen insensitivity syndrome (AIS) is associated with mutations
      throughout the androgen receptor (AR) gene. Different mutations at the same codon
      have been identified in individuals with various phenotypes suggesting the nature
      of the codon substituted may influence the degree of AIS. We investigated if
      phenotype could be predicted by comparing the functionality of AR mutations with
      those at the same codon of known phenotype. PATIENTS: We identified patients from
      the Cambridge Disorders of Sex Development Database with the AR substitutions:
      Phe754Ser with microphallus without hypospadias and Asp690Val with complete AIS.
      Mutations Phe754Leu, Phe754Val and Asp690deletion (Asp690del) have previously
      been reported to be associated with different degrees of AIS. DESIGN: We
      characterized the functional properties of Phe754Ser, Phe754Leu, Phe754Val,
      Asp690Val and Asp690del receptor mutants in vitro and used the crystal structure
      of the AR ligand binding domain to model the mutations. RESULTS: The receptor
      mutants Phe754Ser, Phe754Leu and Phe754Val bound androgen with decreasing
      affinity, while Asp690Val showed reduced affinity compared to Asp690del. A
      similar pattern of reduced activation was seen on androgen responsive elements.
      We suggest how the mutations could affect AR structure, resulting in the observed
      phenotypes. CONCLUSIONS: The relative functional properties of Phe754 and Asp690
      mutant AR receptors correlate broadly with their specific phenotypes. Therefore,
      comparing the molecular consequences of novel mutations with others at the same
      codon may be a useful aid to AIS patient management, particularly for sex of
      rearing decisions when prediction of functionality is important.

PMID- 19178529
TI  - Monitoring disease activity using GH and IGF-I in the follow-up of 501 patients
      with acromegaly.
AB  - CONTEXT: The aims of treatment in patients with acromegaly are to achieve serum
      GH/IGF-I concentrations associated with cure or normalization of mortality and
      alleviation of symptoms. OBJECTIVE AND METHODS: Using the West Midlands
      Acromegaly database (n = 501) we investigated the reliability of basal fasting GH
      in predicting nadir or mean GH during oral glucose tolerance test (OGTT) or GH
      day curve (GHDC), respectively, the degree of discordance between disease
      activity measured by GH and IGF-I values and the effect of radiotherapy on the
      above relationships. In total 773 OGTT and 507 GHDC were performed. RESULTS:
      Basal fasting GH was strongly correlated with nadir/mean GH on OGTT/GHDC (r =
      +0.87, P < 0.0001, r = +0.93, P < 0.0001, respectively). A basal GH < 2.5
      microg/l was associated with a nadir/mean GH during OGTT/GHDC < 2.5 microg/l in
      98.6% and 88.2% of cases, respectively. Elevated IGF-I was seen in 32.4% and
      46.4% of patients with GH nadir values during OGTT < 1 and < 2.5 microg/l,
      respectively, and in 21.2% and 45.9% of GHDC with mean GH < 1 and < 2.5 microg/l,
      respectively. Radiotherapy increased the discordance in GH and IGF-I as markers
      of disease activity at GH < 2.5 microg/l (elevated IGF-I-values when OGTT nadir
      GH < 2.5 microg/l: radiotherapy 55.5%vs. no radiotherapy 36.9%, P = 0.002).
      CONCLUSIONS: There is a close relationship between a basal fasting GH < 2.5
      microg/l and nadir/mean GH < 2.5 microg/l during OGTT/GHDC. There is a large
      discordance between disease activity when assessed by GH and IGF-I which is
      further increased by radiotherapy. These observations illustrate the challenge of
      defining appropriate biochemical end-points to achieve control of disease and
      normalization of mortality in acromegaly.

PMID- 19178530
TI  - Effect of an OT antagonist on the control of the midcycle LH surge in women.
AB  - OBJECTIVE: Data in women regarding the role of OT in LH secretion during the LH
      surge are conflicting. As in previous studies blood samples for LH measurements
      were taken infrequently, we re-examined this matter in women with a fully
      characterized midcycle LH surge. DESIGN: Normal women were studied over two
      cycles. When the dominant follicle reached a diameter of either 16-17 mm (Group
      1) or 18-19 mm (Group 2), the women were infused intravenously for 3 h with
      normal saline (cycle-1) or atosiban (cycle-2). PATIENTS: Fifteen women (10 in
      group 1 and 5 in group 2) aged 23-35 years. MEASUREMENTS: Blood samples were
      obtained every 6 h to characterize the midcycle LH surge. RESULTS: The time
      interval (mean +/- SEM) from the start of the infusion to the onset of the LH
      surge in the two cycles was 46.8 +/- 4.8 and 45.6 +/- 9.6 h in group 1 and 6.0 +/
      2.4 and 7.5 +/- 2.8 h, respectively, in group 2. LH values during the LH surge
      were similar in the two cycles except in group 1 at the point of 30 h at which LH
      value in cycle-2 (41.2 +/- 4.6 mIU/ml) was significantly lower than in cycle-1
      (52.8 +/- 3.4 mIU/ml, P < 0.05). Nevertheless, in each group, the area under the
      curve for LH was similar in the two cycles. CONCLUSIONS: Antagonism of endogenous
      OT action by atosiban does not alter the LH profile during a fully characterized
      midcycle LH surge, suggesting that OT is not a major regulator of LH secretion in
      women.

PMID- 19178532
TI  - The effects of metformin on endogenous androgens and SHBG in women: a systematic
      review and meta-analysis.
AB  - OBJECTIVES: Elevated circulating androgens are risk factors for several chronic,
      metabolic and reproductive disorders. Metformin is an insulin-sensitizing agent
      that may lower androgen levels. To evaluate the effects of metformin on
      endogenous androgens and SHBG levels in women, we conducted a systematic review
      and meta-analysis of randomized controlled trials (RCTs) comparing metformin with
      placebo or no treatment. DATA SOURCE: We used OVID to search MEDLINE, EMBASE and
      CENTRAL until March 2007. REVIEW METHODS: Two reviewers independently extracted
      data on methodological quality, participants, interventions and outcomes of
      interest. Our a priori primary outcome was post-treatment measurements. In a
      secondary analysis, we evaluated the difference between the pre- and post
      treatment levels. We computed the weighted mean difference (WMD) as a measure of
      effect for each outcome using the DerSimonian-Laird random effects method. We
      used the I2 statistic to assess heterogeneity and explored its causes in subgroup
      analyses of features related to participants' characteristics and study design.
      Based on a regression model, we conducted sensitivity analyses by investigating
      the use of placebo as a predictor of effect size. RESULTS: Twenty RCTs fulfilled
      the inclusion criteria. Pooled WMDs in post-treatment levels between the
      metformin and control group were -0.31 nmol/l (95% CI -0.65 to 0.03) for total
      testosterone (TT), 0.10 pmol/l (95% CI -0.89 to 1.10) for free testosterone (FT),
      0.14 micromol/l (95% CI -0.34 to 0.62) for dehydroepiandrosteronesulfate (DHEAS),
      -0.60 nmol/l (95% CI -1.67 to 0.46) for androstenedione (AND) and 5.88 nmol/l
      (95% CI 2.01-9.75) for SHBG. Pooled WMDs of the pre- to post-treatment
      differences (i.e. with adjustment for baseline hormone levels) were -0.38 (95% CI
      -0.51 to -0.25) for TT, -2.71 (95% CI -10.35 to 4.93) for FT, -0.50 (95% CI -0.83
      to -0.16) for DHEAS, -1.39 (95% CI -2.30 to -0.49) for AND and 6.63 (95% CI 2.32
      10.94) for SHBG. In subgroup analyses, features related to the administered
      treatment (i.e. metformin as a single agent or as part of combined regimens)
      partly explained the heterogeneity. Sensitivity analyses of studies using placebo
      showed similar results to those not using placebo. CONCLUSIONS: Our systematic
      review and meta-analysis provides evidence of metformin-induced changes in
      circulating androgens and SHBG levels in women but the quality of evidence is not
      high. However, there are no data from RCTs regarding these effects in
      postmenopausal women or healthy premenopausal women. High-quality RCTs are
      required to evaluate whether metformin has effects on surrogate markers and
      patient-important outcomes in these patient groups.

PMID- 19178531
TI  - An abnormal screening glucose challenge test in pregnancy predicts postpartum
      metabolic dysfunction, even when the antepartum oral glucose tolerance test is
      normal.
AB  - OBJECTIVE: In pregnancy, a normal result on the oral glucose tolerance test
      (OGTT) that follows an abnormal screening glucose challenge test (GCT) is
      considered a reassuring finding, requiring no further intervention. The
      obstetrical and metabolic implications of this presentation, however, have not
      been well studied. Thus, we sought to characterize the obstetrical and postpartum
      metabolic significance of an abnormal GCT in women with normal glucose tolerance
      (NGT) on antepartum OGTT. DESIGN/PATIENTS/MEASUREMENTS: A total of 259 women with
      NGT on antepartum OGTT (166 with an abnormal GCT and 93 with a normal GCT)
      underwent (i) metabolic evaluation in pregnancy, (ii) assessment of obstetrical
      outcome at delivery and (iii) repeat metabolic characterization by OGTT at 3
      months postpartum. RESULTS: Neither infant birthweight nor Caesarean section rate
      differed between the abnormal GCT and normal GCT groups. At 3 months postpartum,
      however, compared to the normal GCT group, the abnormal GCT group exhibited
      greater glycaemia (mean area under the glucose curve (AUC(gluc)) 19.6 vs. 18.3, P
      = 0.0021), lower insulin sensitivity (median insulin sensitivity index (IS(OGTT))
      9.5 vs. 11.3, P = 0.0243) and poorer beta-cell function (median insulinogenic
      index/Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) 9.8 vs. 14.1,
      P = 0.0013). On multiple linear regression analyses, an abnormal GCT emerged as
      (i) the strongest independent predictor of postpartum AUC(gluc) (t = 2.77, P =
      0.006) and (ii) the strongest independent negative predictor of log insulinogenic
      index/HOMA-IR (t = -2.36, P = 0.0191). Furthermore, the GCT was the antepartum
      parameter that best predicted postpartum pre-diabetes (area under the receiver
      operating characteristic curve (AROC) = 0.754). CONCLUSIONS: An abnormal
      antepartum GCT, even when followed by a normal OGTT, is associated with
      postpartum glycaemia and beta-cell dysfunction, factors that may portend an
      increased future risk of diabetes in this patient population.

PMID- 19178533
TI  - Evidence that PKA activity is constitutively activated in human GH-secreting
      adenoma cells in a patient with Carney complex harbouring a PRKAR1A mutation.
AB  - CONTEXT: The GHRH-protein kinase A (PKA) signalling pathway is essential for cell
      proliferation and GH synthesis/secretion in somatotrophs. An inactivating
      mutation of PRKAR1A is one of the causes of somatotrophinoma in Carney complex
      (CNC). The basal PKA activity of somatotroph adenoma cells from CNC has not been
      evaluated because of a limited amount of available tissue. OBJECTIVE: This study
      examined how the PRKAR1A mutation affects the PKA signalling pathway in a human
      somatotrophinoma with a PRKAR1A mutation. DESIGN AND SETTING: Somatotrophinoma
      cells from a 40-year-old male patient with CNC were used. The patient had a novel
      somatic heterozygous germline frameshift mutation (227delT) in PRKAR1A leading to
      a premature stop codon. The tumour showed loss of heterozygosity (LOH) at 17q23
      24. Primary cultured adenoma cells were subjected to electrophysiological
      experiments to evaluate PKA signalling in individual cells. RESULTS: GHRH did not
      increase the nonselective cation current or the voltage-gated calcium current in
      these adenoma cells, in contrast to nonadenomatous somatotroph cells in which
      these currents increase through the PKA pathway. Application of a PKA inhibitor
      inhibited the basal currents in these adenoma cells, results that were not
      observed in nonadenomatous somatotrophs. These data indicate that the basal
      currents are already increased and cannot be further increased by GHRH.
      CONCLUSIONS: The results demonstrate that PKA is activated at the basal state in
      these adenoma cells. The data also show that both the nonselective cation current
      and the voltage-gated calcium current, vital regulators of GH secretion
      downstream of PKA, are maximally increased in these cells. These maximally
      increased currents probably account for the excessive GH secretion.

PMID- 19178535
TI  - Beta lactam allergy and resensitization in children with suspected beta lactam
      allergy.
AB  - BACKGROUND: In patients who were clinically diagnosed as having beta lactam
      allergy and had negative skin tests, the rates of reported resensitization to
      beta lactams after subsequent exposures, vary significantly. Some allergists
      advocate skin testing before every exposure to beta lactams. OBJECTIVE: We sought
      to determine the true rate of beta lactam allergy and of resensitization in
      children with a positive history for suspected beta lactam allergy. METHODS: The
      study was conducted from July 1998 to May 2004, with follow-up during 2007. Beta
      lactam allergy tests with the major determinant and freshly prepared minor
      determinant mixtures were offered to history positive children. Negative skin
      tests were followed by oral challenge. The tests were performed again 1-5 months
      later in order to address the possibility of resensitization. RESULTS: Tests were
      performed on 166 children: 150 for penicillins alone, 14 for penicillin in
      combination with cephalosporins, and an additional 2 patients solely for
      cephalosporins. Only 10 children (6%) were positive in the initial evaluation,
      four by skin test and six by oral challenge. A second set of tests was performed
      in 98 children with a negative initial evaluation; only two children (2%) were
      resensitized. On a follow-up survey of 71 of the 96 patients, 59 (83%) had
      received beta lactams; only one had developed a minor rash after subsequent
      exposure to amoxicillin. CONCLUSIONS: Most children with suspected beta lactam
      allergy were not allergic to beta lactams. Resensitization to beta lactam
      antibiotics in children in this study was infrequent. In children with a clinical
      diagnosis of beta lactam allergy and negative skin tests, repeated skin testing
      before every exposure is usually unnecessary.

PMID- 19178534
TI  - Endogenous sex steroid hormones and measures of chronic kidney disease (CKD) in a
      nationally representative sample of men.
AB  - CONTEXT: Sex steroid hormones may play a role in the pathogenesis of chronic
      kidney disease (CKD). OBJECTIVE: To determine whether sex steroid hormone
      concentrations are associated with kidney function or kidney damage in men in the
      general US population. We hypothesized that lower serum testosterone and E(2)
      concentrations are associated with CKD. DESIGN PATIENTS AND MEASUREMENTS: Serum
      sex steroid hormones were measured by electrochemiluminescence immunoassays for
      1470 men who attended the morning session of Phase I of the Third National Health
      and Nutrition Examination Survey (NHANES III). We used two measures of CKD,
      estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2) calculated
      using serum creatinine or cystatin C levels and the abbreviated Modification of
      Diet in Renal Disease Study formulae and urinary albumin : creatinine ratio
      (UACR) >or= 17 mg/g. RESULTS: Mean free testosterone concentration was higher in
      men with an eGFR < 60 ml/min/1.73 m(2) than in men with a higher eGFR. In
      multivariable adjusted models, the odds of an eGFR < 60 ml/min/1.73 m(2) or UACR
      >/= 17 mg/g did not differ across tertiles of hormones with the exception of free
      E(2); those in the highest vs. lowest tertile had an elevated odds of decreased
      eGFR (OR: 3.04, 95% CI (1.22, 7.57); P-trend = 0.02). CONCLUSIONS: In a
      nationally representative sample of US adult men, higher free E(2) concentration
      was significantly associated with an eGFR < 60 ml/min/1.73 m(2) as assessed by
      serum creatinine or cystatin C even after multivariable adjustment. These
      findings are in contrast to the hypothesis that oestrogens may protect against
      CKD, though reverse causation cannot be ruled out. Longitudinal investigation of
      the role of oestrogens in kidney haemodynamics, function, and pathophysiology is
      warranted.

PMID- 19178536
TI  - High-fat feeding redirects cytokine responses and decreases allergic airway
      eosinophilia.
AB  - BACKGROUND: Dietary fat intake has been associated with obesity and obesity in
      its turn with attenuated airway function and asthma, but it is unclear whether or
      how high-fat intake per se alters immune function relevant to development of
      allergic asthma. OBJECTIVE: To use a non-obese mouse model of mild to moderate
      allergic asthma to compare effects of high-fat with isocaloric control-diet on
      allergic immune responses. METHODS: C57BL/6 mice weaned and maintained on control
      (11% fat calories) or isocaloric high-fat diet (58% fat calories) were
      systemically sensitized with ovalbumin and challenged in the lungs. Allergic
      airway inflammation was assessed by measuring lung inflammation; serum
      antibodies; and, cytokines in serum, bronchoalveolar lavage (BAL) fluid and in
      supernatants of in vitro stimulated lung draining lymph node and spleen
      lymphocytes. RESULTS: There was a significant reduction in lung eosinophilia and
      IL-5 in high-fat fed mice. Lung draining lymph node cells from these mice showed
      reduced pro-inflammatory cytokine (MCP-1 and TNF-alpha) release after ovalbumin
      re-stimulation and reduced release of IL-13 after concanavalin-A stimulation,
      indicating a general rather than just an antigen-specific change. There was no
      difference in IFN-gamma release. In contrast, pro-inflammatory cytokine release
      was increased from splenocytes. Decreased eosinophilia was not due to increased
      regulatory T cell or IL-10 induction in draining lymph nodes or spleen, nor to
      changes in antibody response to ovalbumin. However, decreased levels of serum and
      BAL eotaxin were found in high-fat fed animals. CONCLUSIONS: The data indicate
      that high-fat dietary content redirects local immune responses to allergen in the
      lungs and systemic responses in the spleen and serum. These effects are not due
      to changes in regulatory T cell populations but may reflect a failure to mobilize
      eosinophils in response to allergic challenge.

PMID- 19178538
TI  - Airway angiogenesis in patients with rhinitis and controlled asthma.
AB  - BACKGROUND: Airway angiogenesis may be an important part of structural
      remodelling in the pathogenesis of asthma. The development of asthma is
      frequently preceded by rhinitis. OBJECTIVE: We sought to determine whether the
      levels of angiogenesis-related factors are elevated in airways of patients with
      rhinitis or controlled asthma. METHODS: We analysed the induced sputum of 18
      rhinitis patients, 16 asthmatic patients, and 15 healthy controls. The
      concentrations of angiogenin, vascular endothelial growth factor (VEGF), IL-8,
      fibroblast growth factor (bFGF), and TNF-alpha were measured by cytometric bead
      arrays. RESULTS: We found significantly increased angiogenin and VEGF
      concentrations in the induced sputum supernatant of both rhinitis and asthma
      patients compared with that of the healthy control group (P< or =0.0005). With
      the exception of TNF-alpha, there was no difference in the other angiogenic
      factors; TNF-alpha levels were higher in the rhinitis group than in the control
      group (P=0.02). CONCLUSION: These in vivo results suggest increased airway
      angiogenesis in patients with rhinitis without asthma as well as in
      corticosteroid-treated and well-controlled asthma patients.

PMID- 19178539
TI  - Allergenicity and immunogenicity of the major mugwort pollen allergen Art v 1
      chemically modified by acetylation.
AB  - BACKGROUND: Treating allergies with modified allergens is an approach to make the
      treatment safer and more efficient. Art v 1 is the most prominent allergen of
      mugwort pollen and a significant cause of hayfever around Europe. The aim of this
      study was to reduce the allergenicity of Art v 1 by acetylation, and to
      investigate the capacity of the modified protein to generate blocking antibodies.
      METHODS: The reduction of allergenicity of Art v 1 following acetylation was
      monitored by immunoblot, ELISA inhibition using a pool of sera from mugwort
      pollen allergic patients, basophil activation assay and by skin prick testing of
      mugwort-allergic patients. Rabbits were immunized against Art v 1 and acetylated
      Art v 1 (acArt v 1) and the rabbit antisera were tested for their capacity to
      block human IgE binding in ELISA. Human T cell proliferation against Art v 1 and
      acArt v 1 was examined in peripheral blood mononuclear cells (PBMCs) of mugwort
      pollen allergic patients and cytokine release in PBMC cultures was monitored.
      RESULTS: Acetylation of Art v 1 gave a derivative of reduced allergenicity in the
      in vitro and ex vivo tests applied. The skin test reactivity to acArt v 1 was
      significantly reduced in 19 patients when compared with the reactivity to Art v
      1. Rabbit antibodies to acArt v 1 and Art v 1 showed similar capacity to block
      human IgE binding to Art v 1 in inhibition ELISA. Both proteins were able to
      induce proliferation of PBMCs and CD3/CD4(+) cells of mugwort-allergic patients.
      Release of IL-5 was significantly reduced in cultures stimulated with acArt v 1.
      CONCLUSIONS: Art v 1 modified by acetylation had a significantly reduced
      allergenicity in vitro and in vivo, while its immunogenicity was retained.
      Modification of allergens by acetylation could be a new strategy for allergen
      specific immunotherapy.

PMID- 19178537
TI  - Siglec-8 on human eosinophils and mast cells, and Siglec-F on murine eosinophils,
      are functionally related inhibitory receptors.
AB  - Siglecs (sialic acid-binding, Ig-like lectins) are a family of single-pass
      transmembrane cell surface proteins found predominantly on leucocytes. Their
      unique structural characteristics include an N-terminal carbohydrate-binding
      ('lectin') domain that binds sialic acid, followed by a variable number of Ig
      like domains, hence these structures are a subset of the Ig gene superfamily.
      Another unique feature of Siglecs is that most, but not all, possess so-called
      immunoreceptor tyrosine-based inhibitory motifs in their cytoplasmic domains,
      suggesting that these molecules function in an inhibitory capacity. Siglec-8, the
      eighth member identified at the time, was discovered as part of an effort
      initiated almost a decade ago to identify novel human eosinophil and mast cell
      proteins. Since that time, its selective expression on human eosinophils and mast
      cells has been confirmed. On eosinophils, Siglec-8 engagement results in
      apoptosis, whereas on mast cells, inhibition of FcepsilonRI-dependent mediator
      release, without apoptosis, is seen. It has subsequently been determined that the
      closest functional paralog in the mouse is Siglec-F, selectively expressed by
      eosinophils but not expressed on mast cells. Despite only modest homology, both
      Siglec-8 and Siglec-F preferentially recognize a sulphated glycan ligand closely
      related to sialyl Lewis X, a common ligand for the selectin family of adhesion
      molecules. Murine experiments in normal, Siglec-F-deficient mice and
      hypereosinophilic mice have resulted in similar conclusions that Siglec-F, like
      Siglec-8, plays a distinctive and important role in regulating eosinophil
      accumulation and survival in vivo. Given the resurgent interest in eosinophil
      directed therapies for a variety of disorders, plus its unique additional ability
      to also target the mast cell, therapies focusing on Siglec-8 could some day prove
      to be a useful adjunct to our current armamentarium for the treatment of asthma,
      allergies and related disorders where overproduction and overactivity of
      eosinophils and mast cells is occurring.

PMID- 19178540
TI  - Animal models of protein allergenicity: potential benefits, pitfalls and
      challenges.
AB  - Food allergy is an important health issue. With an increasing interest in novel
      foods derived from transgenic crop plants, there is a growing need for the
      development of approaches suitable for the characterization of the allergenic
      potential of proteins. There are methods available currently (such as homology
      searches and serological testing) that are very effective at identifying proteins
      that are likely to cross-react with known allergens. However, animal models may
      play a role in the identification of truly novel proteins, such as bacterial or
      fungal proteins, that have not been experienced previously in the diet. We
      consider here the potential benefits, pitfalls and challenges of the selection of
      various animal models, including the mouse, the rat, the dog and the neonatal
      swine. The advantages and disadvantages of various experimental end-points are
      discussed, including the measurement of specific IgE by ELISA, Western blotting
      or functional tests such as the passive cutaneous anaphylaxis assay, and the
      assessment of challenge-induced clinical symptoms in previously sensitized
      animals. The experimental variables of route of exposure to test proteins and the
      incorporation of adjuvant to increase the sensitivity of the responses are
      considered also. It is important to emphasize that currently none of these
      approaches has been validated for the purposes of hazard identification in the
      context of a safety assessment. However, the available evidence suggests that the
      judicious use of an accurate and robust animal model could provide important
      additional data that would contribute significantly to the assessment of the
      potential allergenicity of novel proteins.

PMID- 19178541
TI  - Conditioned polarized Caco-2 cell monolayers allow to discriminate for the
      ability of gut-derived microorganisms to modulate permeability and antigen
      induced basophil degranulation.
AB  - BACKGROUND: Food allergy is a common allergic disorder--especially in early
      childhood. The avoidance of the allergenic food is the only available method to
      prevent further reactions in sensitized patients. A better understanding of the
      immunologic mechanisms involved in this reaction would help to develop
      therapeutic approaches applicable to the prevention of food allergy. OBJECTIVE:
      To establish a multi-cell in vitro model of sensitized intestinal epithelium that
      mimics the intestinal epithelial barrier to study the capacity of probiotic
      microorganisms to modulate permeability, translocation and immunoreactivity of
      ovalbumin (OVA) used as a model antigen. METHODS: Polarized Caco-2 cell
      monolayers were conditioned by basolateral basophils and used to examine apical
      to basolateral transport of OVA by ELISA. Activation of basophils with
      translocated OVA was measured by beta-hexosaminidase release assay. This
      experimental setting was used to assess how microorganisms added apically
      affected these parameters. Basolateral secretion of cytokine/chemokines by
      polarized Caco-2 cell monolayers was analysed by ELISA. RESULTS: Basophils loaded
      with OVA-specific IgE responded to OVA in a dose-dependent manner. OVA
      transported across polarized Caco-2 cell monolayers was found to trigger
      basolateral basophil activation. Microorganisms including lactobacilli and
      Escherichia coli increased transepithelial electrical resistance while promoting
      OVA passage capable to trigger basophil activation. Non-inflammatory levels of IL
      8 and thymic stromal lymphopoietin were produced basolaterally by Caco-2 cells
      exposed to microorganisms. CONCLUSION: The complex model designed in here is
      adequate to learn about the consequence of the interaction between microorganisms
      and epithelial cells vis-a-vis the barrier function and antigen translocation,
      two parameters essential to mucosal homeostasis. It can further serve as a direct
      tool to search for microorganisms with anti-allergic and anti-inflammatory
      properties.

PMID- 19178542
TI  - Allergen-independent immunomodulatory activities of immunoglobulin E.

PMID- 19178543
TI  - Characterization of the major allergens of Pachycondyla chinensis in ant sting
      anaphylaxis patients.
AB  - BACKGROUND: The ant species Pachycondyla chinensis, which has spread from Far
      Eastern Asia to New Zealand and North America, induces anaphylactic reactions in
      human with its sting. However, the major allergens of P. chinensis have not yet
      been characterized. METHODS: We selected seven patients with histories of
      anaphylaxis induced by P. chinensis. Two-dimensional electrophoresis (2-DE) was
      used to identify the major allergens. We subsequently performed Western blots for
      P. chinensis-specific IgEs, N-terminal amino acid sequencing, ESI-MS/MS, and RT
      PCR using primers based on the N-terminal sequence. RESULTS: Six of the
      anaphylactic subjects had an IgE specific to a 23 kDa allergen of P. chinensis.
      Two candidates for major allergens, 23 kDa (pI 8.7) and 25 kDa (pI 6.2), were
      revealed by 2-DE using P. chinensis-specific IgE immunoblotting. In N-terminal
      sequencing and ESI-MS/MS analysis, 23 kDa (pI 8.7) and 25 kDa (pI 6.2) allergens,
      belonging to the protein families of antigen 5, were identified and share marked
      amino acid sequence similarity. The 23 kDa allergen is 206 amino acids in length
      and homology searches showed 54.0% and 50.0% homology with Sol i 3 and Ves v 5,
      respectively. CONCLUSION: The major allergens of P. chinensis are 23 kDa (pI 8.7)
      and 25 kDa (pI 6.2) proteins that belong to the antigen 5 family of proteins.

PMID- 19178544
TI  - Molecular epidemiological investigation of an outbreak of invasive beta
      haemolytic streptococcal infection in western Norway.
AB  - During a decade-long, high endemic situation with severe group A streptococcal
      disease in western Norway, a cluster of 16 patients with invasive streptococcal
      disease was hospitalized during a period of 11 weeks. A study including clinical
      characteristics and molecular epidemiology of the outbreak was initiated.
      Relevant clinical information was obtained from the medical records of the
      patients. Nine of the 16 patients had soft tissue infection, and seven of these
      had streptococcal toxic shock syndrome (STSS). Mortality, both overall and among
      those with STSS, was 25%. Streptococcal isolates from these patients were
      characterized by serogrouping and emm sequence typing. The emm amplicons were
      further characterized by sequence analysis and restriction fragment length
      polymorphism (emm RFLP) analysis. The streptococci were identified as group A
      streptococcus (GAS) in 11 patients and group G streptococcus (GGS) in four
      patients. The patients with GGS infection were older than the patients with GAS
      infection, and all patients infected with GGS had predisposing comorbidities.
      Isolates from 13 patients were available for emm gene analysis and found to
      belong to nine different emm types. Similar differentiation was obtained with emm
      RFLP in GAS. Hence, the outbreak was polyclonal. Results suggestive of horizontal
      gene transfer and recombination between the emm genes of GAS, group C
      streptococcus and GGS were found in the isolates from seven patients. Such
      genetic recombination events suggest a possible role in pathogenesis.

PMID- 19178545
TI  - The population structure of Staphylococcus aureus among general practice patients
      from The Netherlands.
AB  - To investigate the prevalence, the antibiotic resistance pattern and the
      population structure of Staphylococcus aureus, S. aureus isolates from the
      anterior nostrils of patients of general practitioners (GPs) were analysed.
      Insight into the S. aureus population structure is essential, as nasal carriers
      of S. aureus are at increased risk of developing an S. aureus infection. S.
      aureus was isolated from nasal swabs from 2691 patients with no sign of an
      infection collected in 29 GP practices in The Netherlands. The susceptibility
      pattern for several classes of antibiotics was determined, as well as the S.
      aureus genetic background, using spa typing. S. aureus was isolated from 617 of
      the 2691 (23%) nasal swabs. The prevalences of resistance to ciprofloxacin, co
      trimoxazole, fusidic acid, macrolides and mupirocin were 0.2%, 0%, 6%, 5% and 1%,
      respectively. Half of the isolates were associated with a genetic background
      common to the major methicillin-resistant S. aureus (MRSA) clones, e.g. clonal
      complex (CC)1, CC5, CC8, CC22, CC30 and CC45, and the remainder were mainly
      associated with CC7, CC12, CC15, CC26, CC51 and CC101. The low prevalences of
      resistance suggest that, in the Dutch situation, S. aureus isolates from patients
      visiting their GP because of complaints not related to infection do not represent
      a large reservoir of antibiotic resistance genes. Although no MRSA isolates were
      found, the genetic background of some of the S. aureus isolates is commonly
      observed among community-associated (CA)-MRSA clones (CC1, CC8 and CC30), and
      this might suggest that these isolates have the potential to become CA-MRSA.

PMID- 19178546
TI  - Chemical, biological and radiological incidents: preparedness and perceptions of
      emergency nurses.
AB  - Despite their important role in chemical, biological and radiological (CBR)
      incident response, little is known about emergency nurses' perceptions of these
      events. The study aim was to explore emergency nurses' perceptions of CBR
      incidents and factors that may influence their capacity to respond. Sixty-four
      nurses from a metropolitan Emergency Department took part. The majority were
      willing to participate in CBR incidents and there was a positive association
      between willingness to participate and postgraduate qualification in emergency
      nursing. Willingness decreased, however, with unknown chemical and biological
      agents. One third of participants reported limitations to using personal
      protective equipment. Few participants had experience with CBR incidents although
      70.3 per cent of participants had undergone CBR training. There were significant
      differences in perceptions of choice to participate and adequacy of training
      between chemical, biological and radiological incidents. The study results
      suggest that emergency nurses are keen to meet the challenge of CBR incident
      response.

PMID- 19178547
TI  - Earthquake recovery of historic buildings: exploring cost and time needs.
AB  - Disaster recovery of historic buildings has rarely been investigated even though
      the available literature indicates that they face special challenges. This study
      examines buildings' recovery time and cost to determine whether their functions
      (that is, their use) and their status (historic or non-historic) affect these
      outcomes. The study uses data from the city of San Francisco after the 1989 Loma
      Prieta earthquake to examine the recovery of historic buildings owned by public
      agencies and non-governmental organisations. The results show that recovery cost
      is affected by damage level, construction type and historic status, whereas
      recovery time is affected by the same variables and also by building function.
      The study points to the importance of pre-incident recovery planning, especially
      for building functions that have shown delayed recovery. Also, the study calls
      attention to the importance of further investigations into the challenges facing
      historic building recovery.

PMID- 19178548
TI  - Putting houses in place: rebuilding communities in post-tsunami Sri Lanka.
AB  - This paper interrogates the social and political geographies of resettlement and
      reconstruction of temporary and permanent shelters, which are fundamental to
      rebuilding tsunami-affected communities. War and ethnic cleavages are an endemic
      feature of Sri Lanka's social polity, and uneven development processes in the
      country are clearly visible. This paper draws attention to these spaces of
      inequality by drawing on in-depth interviews and participant observation carried
      out in Eastern and Southern Sri Lanka. It argues that communities' concerns and
      anxieties regarding displacement and resettlement have tended to be articulated
      against prevailing fault lines of war and inequality. This is the backdrop
      against which communities negotiated the recovery process. My fieldwork shows
      that it is critical to understand that disaster and development relief are
      ingrained within context specificities. Relief efforts therefore need to
      recognise that the process of 'putting houses in place' should be embedded within
      local social relations.

PMID- 19178549
TI  - Inter-organisational communication in civil-military cooperation during complex
      emergencies: a case study in Afghanistan.
AB  - This paper seeks to contribute to an improved information management and exchange
      between humanitarian organisations and military agents in complex emergencies. To
      do so, a theoretical information management process model was developed and
      applied to the case of information management between International Security
      Assistance Force troops and humanitarian organisations such as Cordaid, DACAAR
      and the International Office for Migration in Kabul, Afghanistan. Based on this
      analysis the main shortcomings and problems in each stage of the information
      management process were identified. These include a lack of structured
      information databases, the absence of identification of information needs, and an
      over-classification of documents by the military. Using a logical framework
      analysis, six major improvement tactics were developed, including the creation of
      more overlap in rotations of personnel, the specification of aims and tasks
      regarding information management, the improvement of skills and competences of
      personnel involved, and the introduction of regular joint civil-military
      evaluations.

PMID- 19178550
TI  - The Tasman Spirit oil spill: implications for regulatory change in Pakistan.
AB  - An oil spill in July 2003 from the tanker Tasman Spirit attracted considerable
      public and media attention in Pakistan. This paper focuses on the experience of a
      developing country such as Pakistan in dealing with a major oil spill and its
      impact on bringing about change in the national regulatory framework. A major
      outcome has been the ratification of the International Convention on Civil
      Liability for Oil Pollution Damage 1992, which came into force in March 2006 in
      Pakistan. The convention provides a compensation mechanism for victims incurring
      oil pollution damages from maritime casualties involving oil laden ships. Several
      additional changes are still required to improve the country's ability to cope
      with marine oil spills. These include the development of a comprehensive domestic
      regulatory framework, implementation of an effective contingency plan, and
      capacity building of all relevant agencies.

PMID- 19178551
TI  - Why the poor pay with their lives: oil pipeline vandalisation, fires and human
      security in Nigeria.
AB  - Since its discovery in Nigeria in 1956 crude oil has been a source of mixed
      blessing to the country. It is believed to have generated enormous wealth, but it
      has also claimed a great many lives. Scholarly attention on the impact of oil on
      security in Nigeria has largely focused on internal conflicts rather than on how
      disasters associated with oil pipeline vandalisation have impacted on human
      security in terms of causing bodily injuries and death, destroying livelihoods
      and fracturing families. This paper examines how pipeline vandalisation affects
      human security in these ways. It identifies women and children as those who are
      hardest hit and questions why the poor are the most vulnerable in oil pipeline
      disasters in this country. It recommends the adoption of a comprehensive and
      integrated framework of disaster management that will ensure prompt response to
      key early warning signs, risk-reduction and appropriate mitigation and management
      strategies.

PMID- 19178552
TI  - Stressful but rewarding: Norwegian personnel mobilised for the 2004 tsunami
      disaster.
AB  - Adequate responses to disasters and emergency situations rely, among other
      factors, on coping abilities in disaster workers and emergency personnel. In this
      study, different aspects of disaster-related stressors and training/experience
      were investigated in Norwegian personnel (n = 581) mobilised for the 2004 tsunami
      disaster. The level of stress reactions, measured nine to ten months after the
      tsunami, was relatively low in this sample, indicating that the personnel coped
      well with the challenges of the disaster. The level of intrusive memories was
      higher in disaster-area personnel (n = 335) than in home-base personnel (n =
      246). Stress reactions were significantly associated with witnessing experiences
      (disaster-area group) and with having to reject victims in need of help (both
      groups). Specific preparation for the mission was associated with a lower level
      of stress reactions in disaster-area personnel. Such factors may be considered in
      training and preparation programmes for disaster workers.

PMID- 19178553
TI  - Substance use and functional impairment among adolescents directly exposed to the
      2001 World Trade Center attacks.
AB  - The relationship between exposure to the World Trade Center (WTC) attacks,
      increased substance use, functional impairment and mental health service use,
      controlling for depression and post-traumatic stress disorder, was assessed
      through an in-school survey of directly exposed students (N = 1040) attending the
      five middle and five high schools nearest the WTC. The survey was conducted 18
      months after the attacks. Students with one WTC exposure risk factor had a five
      fold increase in substance use, while those with three or more exposure risks had
      a nearly 19-fold increase. Increased substance use was associated with impaired
      school work, school behaviour and grades. Students reporting increased substance
      use were nearly twice as likely to want help but were no more likely than
      asymptomatic students to receive services. Adolescents reporting increased
      substance use, without co-morbidity, were less likely to receive psychological
      services than others. Attention to the needs of substance-using adolescents
      exposed to disaster is needed.

PMID- 19178554
TI  - Abstracts of the 25th Annual Scientific Meeting of the Australasian College for
      Emergency Medicine. November 23-27, 2008. Wellington, New Zealand.

PMID- 19178557
TI  - Contribution of nitric oxide, superoxide anion, and peroxynitrite to activation
      of mitochondrial apoptotic signaling in hippocampal CA3 subfield following
      experimental temporal lobe status epilepticus.
AB  - PURPOSE: One cellular consequence of status epilepticus is apoptosis in the
      hippocampal CA3 subfield. We evaluated the hypothesis that the repertoire of
      cellular events that underlie such elicited cell death entails mitochondrial
      dysfunction induced by an excessive production of nitric oxide synthase II (NOS
      II)-derived NO, increased superoxide anion (O(2)(-)) production, and
      peroxynitrite formation. METHODS: In Sprague-Dawley rats, kainic acid was
      microinjected unilaterally into the hippocampal CA3 subfield to induce bilateral
      seizure-like electroencephalography (EEG) activity. The effects of pretreatments
      with various test agents on the induced O(2)(-) production, peroxynitrite
      formation, mitochondrial respiratory chain enzyme activities, cytochrome
      c/caspase-3 signaling, and DNA fragmentation in bilateral CA3 subfields were
      examined. RESULTS: Significantly and temporally correlated increase in O(2)(-)
      and peroxynitrite levels (3 to 24 h), depressed mitochondrial Complex I activity
      (3 h), enhanced translocation of cytochrome c to cytosol (day 1), and augmented
      activated caspase-3 (day 7) and DNA fragmentation (day 7) were detected
      bilaterally in hippocampal CA3 subfields after the elicitation of sustained
      seizure. Pretreatment with microinjection into the bilateral hippocampal CA3
      subfield of a water-soluble formulation of coenzyme Q(10); a selective NOS II
      inhibitor, S-methylisothiourea; a superoxide dismutase mimetic, 4-hydroxy-2,2,6,6
      tetramethylpiperidine-1-oxyl; an active peroxynitrite decomposition catalyst,
      5,10, 15,20-tetrakis-(N-methyl-4-pyridyl)- porphyrinato iron (III); or a
      peroxynitrite scavenger, L-cysteine significantly blunted these cellular events.
      DISCUSSION: Prolonged seizures prompted NO-, O(2)(-)-, and peroxynitrite
      dependent reduction in mitochondrial respiratory enzyme Complex I activity,
      leading to cytochrome c/caspase-3-dependent apoptotic cell death in the
      hippocampal CA3 subfield after induction of experimental temporal lobe status
      epilepticus.

PMID- 19178556
TI  - Epileptiform synchronization in the cingulate cortex.
AB  - PURPOSE: The anterior cingulate cortex (ACC)--which plays a role in pain,
      emotions and behavior--can generate epileptic seizures. To date, little is known
      on the neuronal mechanisms leading to epileptiform synchronization in this
      structure. Therefore, we investigated the role of excitatory and inhibitory
      synaptic transmission in epileptiform activity in this cortical area. In
      addition, since the ACC presents with a high density of opioid receptors, we
      studied the effect of opioid agonism on epileptiform synchronization in this
      brain region. METHODS: We used field and intracellular recordings in conjunction
      with pharmacological manipulations to characterize the epileptiform activity
      generated by the rat ACC in a brain slice preparation. RESULTS: Bath-application
      of the convulsant 4-aminopyridine (4AP, 50 microM) induced both brief and
      prolonged periods of epileptiform synchronization resembling interictal- and
      ictal-like discharges, respectively. Interictal events could occur more
      frequently before the onset of ictal activity that was contributed by N-methyl-D
      aspartate (NMDA) receptors. Mu-opioid receptor activation abolished 4AP-induced
      ictal events and markedly reduced the occurrence of the pharmacologically
      isolated GABAergic synchronous potentials. Ictal discharges were replaced by
      interictal events during GABAergic antagonism; this GABA-independent activity was
      influenced by subsequent mu-opioid agonist application. CONCLUSIONS: Our results
      indicate that both glutamatergic and GABAergic signaling contribute to
      epileptiform synchronization leading to the generation of electrographic ictal
      events in the ACC. In addition, mu-opioid receptors appear to modulate both
      excitatory and inhibitory mechanisms, thus influencing epileptiform
      synchronization in the ACC.

PMID- 19178558
TI  - Serum concentration/dose ratio of topiramate during pregnancy.
AB  - PURPOSE: To study the impact of pregnancy on the serum concentration/dose ratio
      (C/D-ratio) of topiramate (TPM). METHODS: Twelve women with epilepsy using TPM
      during pregnancy, and 15 pregnancies were studied. The main target variable was
      the C/D-ratio at baseline and during pregnancy. Additional variables were changes
      in TPM dose, concomitant use of other antiepileptic drugs, seizure frequency, and
      pregnancy outcome. Clinical and pharmacological data were obtained from the
      women's medical records. RESULTS: The average C/D-ratios in the second and third
      trimester were 30% (p = 0.002, n = 11) and 34% (p = 0.001, n = 8) lower than the
      baseline values, respectively. The interindividual variability was pronounced.
      Increased seizure frequency was common in pregnant women using TPM, but a
      correlation to the decline in TPM C/D-ratio could not be established from our
      data. DISCUSSION: Dose-corrected serum concentrations of TPM appear to decline
      gradually throughout pregnancy. The underlying mechanisms are not known.
      Increased glomerular filtration may play a major role. During pregnancy,
      therapeutic drug monitoring of TPM may be useful.

PMID- 19178559
TI  - Retarded kindling progression in mice deficient in the extracellular matrix
      glycoprotein tenascin-R.
AB  - PURPOSE: We investigated the role of the extracellular matrix glycoprotein
      tenascin-R (TNR) in formation of a hyperexcitable network in the kindling model
      of epilepsy. The idea that TNR may be important for this process was suggested by
      previous studies showing that deficiency in TNR leads to abnormalities in
      synaptic plasticity, perisomatic GABAergic inhibition and more astrocytes in the
      hippocampus of adult mice. METHODS: Constitutively TNR deficient (TNR-/-) mice
      and their wild-type littermates received repeated electrical stimulation in the
      amygdala over several days until they developed fully kindled generalized
      seizures at which time their brains were studied immunohistochemically. RESULTS:
      In TNR-/- mice, kindling progression was retarded compared with wild-type
      littermate controls. Morphological analysis of the mice used for the kindling
      studies revealed that, independently of genotype, numbers of parvalbumin-positive
      interneurons in the dentate gyrus correlated positively with afterdischarge
      threshold alterations in kindled mice. The kindling-induced increase in the
      number of S100 expressing astrocytes in the dentate gyrus was enhanced by TNR
      deficiency and correlated negatively with the kindling rate. DISCUSSION: Our data
      support the view that TNR promotes formation of a hyperexcitable network during
      kindling and suggest that an increase in S100-expressing astrocytes may
      contribute to retarded epileptogenesis in TNR-/- mice.

PMID- 19178560
TI  - Pharmacodynamic and pharmacokinetic interactions between common antiepileptic
      drugs and acetone, the chief anticonvulsant ketone body elevated in the ketogenic
      diet in mice.
AB  - PURPOSE: Acetone is the principal ketone body elevated in the ketogenic diet
      (KD), with demonstrated robust anticonvulsant properties across a variety of
      seizure tests and models of epilepsy. Because the majority of patients continue
      to receive antiepileptic drugs (AEDs) during KD treatment, interactions between
      acetone and AEDs may have important clinical implications. Therefore, we
      investigated whether acetone could affect the anticonvulsant activity and
      pharmacokinetic properties of several AEDs against maximal electroshock (MES)
      induced seizures in mice. METHODS: Effects of acetone given in subthreshold doses
      were tested on the anticonvulsant effects of carbamazepine (CBZ), lamotrigine
      (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), topiramate (TPM)
      and valproate (VPA) against MES-induced seizures in mice. In addition, acute
      adverse effects of acetone-AEDs combinations were assessed in the chimney test
      (motor performance) and passive avoidance task (long-term memory).
      Pharmacokinetic interactions between acetone and AEDs were also studied in the
      mouse brain tissue. RESULTS: Acetone (5 or 7.5 mmol/kg, intraperitoneally [i.p.])
      enhanced the anticonvulsant activity of CBZ, LTG, PB, and VPA against MES-induced
      seizures; effects of OXC, PHT, and TPM were not changed. Acetone (7.5 mmol/kg)
      did not enhance the acute adverse-effect profiles of the studied AEDs. Acetone (5
      or 7.5 mmol/kg, i.p.) did not affect total brain concentrations of the studied
      AEDs. In contrast, VPA, CBZ, LTG, OXC, and TPM significantly decreased the
      concentration of free acetone in the brain; PB and PHT had no effect.
      CONCLUSIONS: Acetone enhances the anticonvulsant effects of several AEDs such as
      VPA, CBZ, LTG, and PB without affecting their pharmacokinetic and side-effect
      profiles.

PMID- 19178561
TI  - Polymorphism of the MDR1/ABCB1 C3435T drug-transporter and resistance to
      anticonvulsant drugs: a meta-analysis.
AB  - BACKGROUND: Approximately one-third of patients with epilepsy patients have
      recurrent seizures despite therapy. It has been suggested that therapeutic
      failure is associated with high expression of the multidrug efflux ABCB1 (MDR1)
      drug-transporter; specifically, that patients with the 3435CC genotype have
      higher efflux of anticonvulsants out of brain tissue, with correspondingly lower
      concentrations in the central nervous system. METHODS: We conducted a meta
      analysis to examine the association between MDR1 polymorphisms and the response
      to anticonvulsants. We included all published studies until September 2007, in
      which patients with responsive and unresponsive seizure disorders underwent
      genotyping for ABCB1 C3435T. Individual and summary odds ratios were calculated
      using a random effects model. A secondary analysis was also performed,
      stratifying the studies by their ethnic distribution to account for genetic
      heterogeneity. We also performed a cumulative analysis by date of publication for
      the included studies using a random effects model. RESULTS: We identified 11 case
      control studies involving 3,371 patients (1,646 patients with drug-resistant
      epilepsy and 1,725 controls). We identified no significant association between
      anticonvulsant drug resistance and MDR1 polymorphism [odds ratio 1.15; 95%
      confidence interval (CI) 0.78-1.70; p = 0.48). Subanalysis of studies according
      to ethnicity yielded similar findings [European cohort: OR = 1.31; 95% CI 0.89
      1.94, p = 0.18; Asian cohort: OR = 0.99; 95% CI 0.51-1.89, p = 0.96).
      CONCLUSIONS: We found no association between ABCB1 genotype and response to
      anticonvulsant drugs. At the present time, genetic typing for MDR1 polymorphism
      is not warranted for patients with drug-resistant epilepsy.

PMID- 19178562
TI  - Labor market participation following onset of seizures and early epilepsy:
      Findings from a UK cohort.
AB  - PURPOSE: Previous studies have reported a considerable employment disadvantage
      among people with epilepsy. In a cohort of men and women who had experienced a
      single seizure or had early epilepsy at study entry we explored employment status
      and social mobility over 4 years and investigated whether employment outcomes
      were more disadvantageous for certain social groups. METHODS: Analyses were based
      on 350 individuals of working age identified via the UK Multicentre Study of
      Early Epilepsy and Single Seizures. Employment rates were calculated for the
      cohort and general population. Employment trajectories over 4 years were explored
      according to occupational social class. The relative risk of employment was
      calculated by clinical features of seizures and social class. RESULTS:
      Individuals with single seizures or early epilepsy had significantly lower
      employment rates than the general population at study entry, and 2- and 4-year
      follow-up. Employment rates of men and women in the cohort did not differ
      significantly. Although little social class mobility occurred during follow-up,
      there was evidence of some downward mobility between first seizure(s) and study
      entry. In the fully adjusted model, nonemployment was predicted at all time
      points by having fair/poor self-rated health and experiencing four or more
      seizures. We observed that some individuals continued to work in hazardous
      occupations or drive professionally within a year of experiencing seizure(s).
      DISCUSSION: People who have recently experienced a single seizure or who have
      early epilepsy are exposed to substantial employment disadvantage. Greater
      efforts are necessary to help these people return to work and stay employed.

PMID- 19178563
TI  - The role of titration schedule of topiramate for the development of depression in
      patients with epilepsy.
AB  - PURPOSE: To determine whether a fast titration schedule of topiramate (TPM) has
      different effects on the occurrence of depression, in relation to other risk
      factors for TPM-induced depression, including history of depression (HxDEP),
      febrile seizures (FS), and hippocampal sclerosis (HS). METHODS: Using data from a
      large case registry of patients prescribed TPM, two models were constructed:
      Model 1 examined the independent effect of rapid TPM titration after separate
      adjustment for FS, HxDEP, and HS. Model 2 examined effect of the cooccurrence of
      rapid titration on the development of depression with each of these risk factors.
      RESULTS: A total of 423 patients were included (51.8% females), mean age (SD)
      35.5 (11.8) years, mean duration of epilepsy of 22.2 (11.5) years. Forty-four
      patients (10.4%) developed depression during TPM therapy. A rapid TPM titration
      was associated with 5-fold increased risk of depression that increased to 12.7
      fold in the presence of both FS and rapid TPM titration, 23.3-fold in the
      presence of both HxDEP and rapid TPM titration, and 7.6-fold in the presence of
      both HS and rapid TPM titration schedule. CONCLUSIONS: Our study suggests that a
      rapid titration schedule is associated with an increased risk of developing
      depression during TPM therapy. HxDEP and FS are major contraindications to the
      use of a rapid titration, with a 23.3-fold and 12.7 fold increased risk,
      respectively.

PMID- 19178564
TI  - Seizure metaphors differ in patients' accounts of epileptic and psychogenic
      nonepileptic seizures.
AB  - PURPOSE: To increase understanding of the subjective symptomatology of seizure
      experiences and improve differential diagnosis by studying the seizure metaphors
      used by patients with (psychogenic) nonepileptic seizures (NES) and epilepsy.
      METHODS: Twenty-one unselected patients taking part in this study were admitted
      for 48 h of video-EEG (electroenceophalography) observation because of
      uncertainty about the diagnosis. Eight were proven to have epilepsy, 13 to have
      psychogenic nonepileptic seizures (PNES). During their admission, patients were
      interviewed by a neurologist. A linguist blinded to the medical diagnosis
      identified and categorized all seizure metaphors in verbatim transcripts. Between
      group comparisons and logistic regression analysis were carried out. RESULTS: Of
      382 metaphors identified, 80.8% conceptualized seizures as an agent/force,
      event/situation, or space/place. Most patients used metaphors from all
      categories, but patients with epilepsy and PNES showed preferences for different
      metaphoric concepts (differences p = 0.009 to p = 0.039). Patients with epilepsy
      preferred metaphors depicting the seizure as an agent/force or event/situation.
      PNES patients more often used metaphors of space/place. Logistic regression
      analyses predicted the diagnosis of PNES or epilepsy correctly in 85.7% of cases
      (based on different metaphor types in the each category) or 81.0% (based on all
      metaphor tokens). DISCUSSION: Patients with epilepsy and PNES have different
      preferences in the metaphoric conceptualization of their seizures. Epileptic
      seizures are described as a more external, self-directed entity than PNES, which
      are depicted as a state or place patients go through. The differentiating value
      of metaphoric conceptualizations suggests that metaphor preference could form the
      basis of future diagnostic questionnaires or other diagnostic tools.

PMID- 19178565
TI  - Socioeconomic deprivation independent of ethnicity increases status epilepticus
      risk.
AB  - BACKGROUND: A higher incidence of convulsive status epilepticus (CSE) has been
      reported in nonwhite compared to white populations. Socioeconomic factors can be
      intricately involved in observed ethnic "effects," and the importance of
      socioeconomic status on health conditions is widely recognized. Understanding the
      effect of socioeconomic factors on CSE would provide insights into etiology and
      management, leading to the development of novel prevention strategies. METHODS:
      From a population-based UK study on childhood CSE, we tested the hypothesis that
      socioeconomic deprivation independent of ethnicity increases the risk of
      childhood CSE. Home postal codes were used to measure the socioeconomic status of
      the neighborhood in which patients lived relative to that of the borough in which
      the neighborhood was located. The child's ethnicity was reported by parent(s).
      Relationships between socioeconomic status, ethnicity, and incidence were
      investigated using Poisson regression analysis. RESULTS: A total of 176 children
      were enrolled. The incidence of CSE in nonwhite children [18.5, 95% confidence
      interval (CI) 13.7-23.3/100,000/year] was 1.8 (95% CI 1.3-2.4) times greater than
      for white children (10.5, 95% CI 7.9-13.1/100,000/year) (p < 0.0005).
      Socioeconomic deprivation and Asian ethnicity were independently associated with
      increased incidence. For each point increase in Index of Multiple Deprivation
      (IMD) 2004, there was a 1.03 cumulative increased relative risk (95% CI 1.01
      1.06, p = 0.007). Asian children were 5.7 times (95% CI 1.7-18.9) more likely
      than white children to have a first-ever episode of CSE (p = 0.004).
      Socioeconomic and ethnicity effects were related to etiology of CSE.
      INTERPRETATION: Ethnic and socioeconomic factors independently affect risk for
      prolonged febrile seizures and acute symptomatic CSE, but not for other types of
      childhood CSE.

PMID- 19178567
TI  - Integrative approaches for assessing the ecological sustainability of in situ
      bioremediation.
AB  - Application of microbial metabolic potential (bioremediation) is accepted as an
      environmentally benign and economical measure for decontamination of polluted
      environments. Bioremediation methods are generally categorized into ex situ and
      in situ bioremediation. Although in situ bioremediation methods have been in use
      for two to three decades, they have not yet yielded the expected results. Their
      limited success has been attributed to reduced ecological sustainability under
      environmental conditions. An important determinant of sustainability of in situ
      bioremediation is pollutant bioavailability. Microbial chemotaxis is postulated
      to improve pollutant bioavailability significantly; consequently, application of
      chemotactic microorganisms can considerably enhance the performance of in situ
      degradation. The environmental fate of degradative microorganisms and the
      ecological consequence of intervention constitute other important descriptors for
      the efficiency and sustainability of bioremediation processes. Integrative use of
      culture-dependent, culture-independent methods (e.g. amplified rDNA restriction
      analysis, terminal restriction fragment length polymorphism, denaturing/thermal
      gradient gel electrophoresis, phospholipid fatty acid, etc.), computational and
      statistical analyses has enabled successful monitoring of the above aspects. The
      present review provides a detailed insight into some of the key factors that
      affect the efficiency of in situ bioremediation along with a comprehensive
      account of the integrative approaches used for assessing the ecological
      sustainability of processes. The review also discusses the possibility of
      developing suicidal genetically engineered microorganisms for optimized and
      controlled in situ bioremediation.

PMID- 19178570
TI  - Springs and the origin of bourbon.

PMID- 19178566
TI  - Genomic islands: tools of bacterial horizontal gene transfer and evolution.
AB  - Bacterial genomes evolve through mutations, rearrangements or horizontal gene
      transfer. Besides the core genes encoding essential metabolic functions,
      bacterial genomes also harbour a number of accessory genes acquired by horizontal
      gene transfer that might be beneficial under certain environmental conditions.
      The horizontal gene transfer contributes to the diversification and adaptation of
      microorganisms, thus having an impact on the genome plasticity. A significant
      part of the horizontal gene transfer is or has been facilitated by genomic
      islands (GEIs). GEIs are discrete DNA segments, some of which are mobile and
      others which are not, or are no longer mobile, which differ among closely related
      strains. A number of GEIs are capable of integration into the chromosome of the
      host, excision, and transfer to a new host by transformation, conjugation or
      transduction. GEIs play a crucial role in the evolution of a broad spectrum of
      bacteria as they are involved in the dissemination of variable genes, including
      antibiotic resistance and virulence genes leading to generation of hospital
      'superbugs', as well as catabolic genes leading to formation of new metabolic
      pathways. Depending on the composition of gene modules, the same type of GEIs can
      promote survival of pathogenic as well as environmental bacteria.

PMID- 19178571
TI  - Travel time distributions derived from particle tracking in models containing
      weak sinks.
AB  - A travel time distribution based on a particle-tracking analysis in a ground
      water model containing weak sinks is often uncertain because whether a particle
      is discharged or allowed to pass through a weak sink is unresolved by particle
      tracking theory. We present a probability-based method to derive an objective
      travel time distribution in models containing weak sinks. The method discharges a
      fraction of the particle at the weak sink and allows the remaining fraction to
      pass through the weak sink. The weight of the discharged fraction depends on the
      ratio of the sink flux to the influx into the weak sink cell. We tested this
      approach on a coarse (100 x 100 m) and a fine (25 x 25 m) horizontal resolution
      regional scale ground water model (34.5 x 24 km). We compared the travel time
      distributions in a small subcatchment derived from particle-tracking analysis
      with one derived from a transport model. We found that the particle-tracking
      analysis with the coarse model underestimated the travel time distribution of the
      catchment compared to the transport solution or a particle-tracking analysis with
      the fine model. The underestimation of travel times with the coarse model was a
      result of a large area covered by sink cells in this model and the more accurate
      flow patterns simulated by the fine model. The probability-based method presented
      here compares favorably with a solute transport solution and provides an accurate
      travel time distribution when used with a fine-resolution ground water model.

PMID- 19178573
TI  - Secondary headache in secondary syphilis.
AB  - We describe a patient with a history of recurrent headaches who developed severe
      and persistent left fronto-orbital and vertex head pain, in conjunction with a
      maculopapular rash, and was subsequently diagnosed with secondary syphilis. With
      the incidence of syphilis recently on the rise, we suggest that secondary
      syphilis should be considered in the differential diagnosis of any patient who
      presents with headache and a rash. Serologic screening tests for syphilis and a
      dermatology consultation should be obtained promptly for diagnostic confirmation
      and institution of treatment with antibiotics.

PMID- 19178572
TI  - A potential-based inversion of unconfined steady-state hydraulic tomography.
AB  - The importance of estimating spatially variable aquifer parameters such as
      transmissivity is widely recognized for studies in resource evaluation and
      contaminant transport. A useful approach for mapping such parameters is inverse
      modeling of data from series of pumping tests, that is, via hydraulic tomography.
      This inversion of field hydraulic tomographic data requires development of
      numerical forward models that can accurately represent test conditions while
      maintaining computational efficiency. One issue this presents is specification of
      boundary and initial conditions, whose location, type, and value may be poorly
      constrained. To circumvent this issue when modeling unconfined steady-state
      pumping tests, we present a strategy that analyzes field data using a potential
      difference method and that uses dipole pumping tests as the aquifer stimulation.
      By using our potential difference approach, which is similar to modeling drawdown
      in confined settings, we remove the need for specifying poorly known boundary
      condition values and natural source/sink terms within the problem domain. Dipole
      pumping tests are complementary to this strategy in that they can be more
      realistically modeled than single-well tests due to their conservative nature,
      quick achievement of steady state, and the insensitivity of near-field response
      to far-field boundary conditions. After developing the mathematical theory, our
      approach is first validated through a synthetic example. We then apply our method
      to the inversion of data from a field campaign at the Boise Hydrogeophysical
      Research Site. Results from inversion of nine pumping tests show expected
      geologic features, and uncertainty bounds indicate that hydraulic conductivity is
      well constrained within the central site area.

PMID- 19178575
TI  - Migrainous prolonged and reversible bilateral inferior altitudinal visual field
      defect.

PMID- 19178574
TI  - Polymorphisms in the renin-angiotensin system and migraine in women.
AB  - BACKGROUND: Recent findings suggest an association between the renin-angiotensin
      system and migraine. However, genetic studies are scarce and controversial.
      OBJECTIVE: To investigate the association between the AGTR1 1166A > C and AGT
      Met235Thr polymorphisms with migraine and migraine aura status. METHODS: We
      performed an association study among 25,000 Caucasian US women, participating in
      the Women's Health Study, with information on the AGTR1 1166A > C and AGT
      Met235Thr polymorphisms. Migraine and migraine aura status were self-reported. We
      distinguished between any history of migraine, active migraine with aura, active
      migraine without aura, and prior migraine (history of migraine, but not in the
      year prior to baseline). We used logistic regression to investigate the genotype
      migraine association. RESULTS: At baseline, 4577 (18.3%) women reported any
      history of migraine; 39.5% of the 3226 women with active migraine indicated aura.
      The polymorphisms were not associated with migraine or migraine-specific
      subgroups. We also did not find a significant interaction between the
      polymorphisms. CONCLUSIONS: Data from this large cohort of Caucasian women do not
      suggest an association of polymorphisms in the renin-angiotensin system with
      migraine or aura status. Future studies should focus on haplotype analyses and
      additional gene-gene as well as gene-environment interactions.

PMID- 19178576
TI  - Is hemicrania continua a single entity or the association of two headache forms?
      Considerations from a case report.
AB  - Hemicrania continua (HC) belongs to the group of primary headaches and it is
      characterized by a strictly unilateral, continuous headache of moderate
      intensity, with superimposed exacerbations of severe intensity that are
      accompanied by trigeminal autonomic features. The syndrome is completely
      responsive to indomethacin. Here we report a case of a 49-year-old man with HC,
      which may be viewed as a combination of different types of headache, ie, chronic
      tension-type headache and trigeminal autonomic cephalalgia. The analysis of this
      case raises interesting issues regarding the proper place of HC among the primary
      headache forms.

PMID- 19178577
TI  - Botulinum toxin a in the treatment of chronic tension-type headache with cervical
      myofascial trigger points: a randomized, double-blind, placebo-controlled pilot
      study.
AB  - OBJECTIVE: To evaluate the efficacy of botulinum toxin A (BT-A) as a prophylactic
      treatment for chronic tension-type headache (CTTH) with myofascial trigger points
      (MTPs) producing referred head pain. BACKGROUND: Although BT-A has received mixed
      support for the treatment of TTH, deliberate injection directly into the cervical
      MTPs very often found in this population has not been formally evaluated.
      METHODS: Patients with CTTH and specific MTPs producing referred head pain were
      assigned randomly to receive intramuscular injections of BT-A or isotonic saline
      (placebo) in a double-blind design. Daily headache diaries, pill counts, trigger
      point pressure algometry, range of motion assessment, and responses to
      standardized pain and psychological questionnaires were used as outcome measures;
      patients returned for follow-up assessment at 2 weeks, 1 month, 2 months, and 3
      months post injection. After 3 months, all patients were offered participation in
      an open-label extension of the study. Effect sizes were calculated to index
      treatment effects among the intent-to-treat population; individual time series
      models were computed for average pain intensity. RESULTS: The 23 participants
      reported experiencing headache on a near-daily basis (average of 27 days/month).
      Compared with placebo, patients in the BT-A group reported greater reductions in
      headache frequency during the first part of the study (P = .013), but these
      effects dissipated by week 12. Reductions in headache intensity over time did not
      differ significantly between groups (P = .80; maximum d = 0.13), although a
      larger proportion of BT-A patients showed evidence of statistically significant
      improvements in headache intensity in the time series analyses (62.5% for BT-A vs
      30% for placebo). There were no differences between the groups on any of the
      secondary outcome measures. CONCLUSIONS: The evidence for BT-A in headache is
      mixed, and even more so in CTTH. However, the putative technique of injecting BT
      A directly into the ubiquitous MTPs in CTTH is partially supported in this pilot
      study. Definitive trials with larger samples are needed to test this hypothesis
      further.

PMID- 19178578
TI  - Early responses in randomized clinical trials of triptans in acute migraine
      treatment. Are they clinically relevant? A comment.
AB  - One can question the clinical relevance of early headache responses after oral
      and intranasal triptans. Thus, for pain-free the early responses were significant
      but in absolute values they were only a few percentages: the therapeutic gains
      (TGs) were 1.8% (95% CI = 0.3-3%) for oral almotriptan 12.5 after 30 minutes and
      1.0% (95% CI = 0-2%) after intranasal zolmitriptan 5 mg after 15 minutes. These
      results are compared with subcutaneous sumatriptan 6 mg which has TGs of 11% (95%
      CI = 7-15%) to 14% (95% CI = 11-17%) for pain-free after 30 minutes. Subcutaneous
      sumatriptan has a 2 times higher response rate than intranasal zolmitriptan and
      is 5 times more effective than oral almotriptan at these early time points. It is
      concluded that if a very early and clinically relevant effect is desired then the
      migraine patient should use the subcutaneous administration form of sumatriptan.

PMID- 19178579
TI  - Symptomatic hypnic headache secondary to a nonfunctioning pituitary macroadenoma.
AB  - We report the case of a woman whose hypnic headache syndrome ceased following
      pituitary tumor removal. Symptomatic hypnic headache cases are rare, but are
      starting to appear in the literature. Until more is known, brain neuroimaging,
      ideally with magnetic resonance imaging, should be considered when the initial
      diagnosis of hypnic headache is made.

PMID- 19178580
TI  - Relationship between basilar-type migraine and migrainous vertigo.
AB  - OBJECTIVE: This study compared clinical manifestations and audiovestibular
      function tests among subjects of basilar-type migraine (BtM), definite and
      probable migrainous vertigo (dMV and pMV), in order to investigate the
      relationship between them. BACKGROUND: Various diagnostic criteria such as BtM,
      dMV, and pMV have been proposed. However, a comparison between these diagnostic
      groups has not been conducted before. METHODS: This study enrolled 77 subjects,
      including BtM in 15, dMV in 30, and pMV in 32 patients. All patients received
      structured interview of clinical presentations and underwent a battery of
      audiovestibular function tests. RESULTS: Demographic features were similar
      between 3 groups, including age, gender, precipitating factors, and family
      preponderance. When considering the clinical manifestations, for example motion
      sickness, migrainous symptoms, and sequential relationship between headache and
      vertigo, BtM and dMV groups shared similar features, but differed from pMV group.
      As regards to differentiate between BtM and dMV patients, the former revealed
      higher occurrence rates than the latter in relation to the frequency of vertigo
      attacks, neurological symptoms, and saccadic dysmetria. CONCLUSION: The
      relationship between BtM, dMV, and pMV refers to a distribution of severity
      across the disease spectrum of migraine-related vertigo. Of them, BtM group
      presents the most severe form in clinical manifestation and brainstem
      involvement, followed by dMV, and pMV is the mildest form.

PMID- 19178581
TI  - Assymetry of temporal artery diameters during spontaneous attacks of cluster
      headache.
AB  - BACKGROUND: Cluster headache is characterized by strictly unilateral head pain
      associated with symptoms of cranial autonomic features. Transcranial Doppler
      studies showed in most studies a bilateral decreased blood flow velocity in the
      middle cerebral artery. OBJECTIVE: To investigate whether there is a bilateral or
      unilateral extracranial vasodilation during spontaneous cluster headache attacks.
      DESIGN AND METHODS: In 9 cluster headache patients, we investigated the luminal
      diameter of the superficial temporal artery with ultrasound on the headache and
      headache-free side during and outside cluster headache attacks. RESULTS: During
      cluster headache attacks, the diameter of the superficial temporal artery on the
      painful side was greater, 1.48 mm, than the diameter on the nonheadache site,
      1.14 mm (P < .01). Outside attacks, median diameters on the 2 sides were quite
      comparable, 1.34 vs 1.31 mm (P = .67). CONCLUSIONS: What was observed is most
      likely a general pain-induced arterial vasoconstriction (confer the decrease in
      diameter on the pain-free side) with an unchanged superficial temporal artery on
      the pain side because of some vasodilator influence.

PMID- 19178582
TI  - Anesthesia provider model, hospital resources, and maternal outcomes.
AB  - OBJECTIVE: Determine the ability of anesthesia provider model and hospital
      resources to explain maternal outcome variation. DATA SOURCE/STUDY SETTING:
      1,141,641 obstetrical patients from 369 hospitals that reported at least one live
      birth in 2002 in six representative states. STUDY DESIGN: Logistic regression of
      death, anesthesia complication, nonanesthesia maternal complication, and
      obstetrical trauma for all patients and those having cesarean deliveries on
      anesthesia provider model, obstetrical and anesthesia, and patient variables.
      DATA COLLECTION/EXTRACTION METHODS: Data was assembled from information given by
      hospitals to state agencies and from a 2004 survey of obstetrical organization
      resources. PRINCIPAL FINDINGS: Anesthesia complication rates in anesthesiologist
      only hospitals were 0.27 percent compared with 0.23 percent in certified
      registered nurse anesthetist (CRNA) only hospitals. Rates among other provider
      models varied from 0.24 to 0.37 percent with none statistically different from
      the anesthesiologist-only hospitals. A similar pattern was observed for rates of
      other outcomes. Multivariate analysis found no systematic differences between
      hospitals with anesthesiologist-only models and models using CRNAs. There was no
      consistent pattern of association of other hospital or patient characteristics
      with outcomes. CONCLUSION: Hospitals that use only CRNAs, or a combination of
      CRNAs and anesthesiologists, do not have systematically poorer maternal outcomes
      compared with hospitals using anesthesiologist-only models.

PMID- 19178583
TI  - Relationship of safety climate and safety performance in hospitals.
AB  - OBJECTIVE: To examine the relationship between measures of hospital safety
      climate and hospital performance on selected Patient Safety Indicators (PSIs).
      DATA SOURCES: Primary data from a 2004 survey of hospital personnel. Secondary
      data from the 2005 Medicare Provider Analysis and Review File and 2004 American
      Hospital Association's Annual Survey of Hospitals. STUDY DESIGN: A cross
      sectional study of 91 hospitals. DATA COLLECTION: Negative binomial regressions
      used an unweighted, risk-adjusted PSI composite as dependent variable and safety
      climate scores and controls as independent variables. Some specifications
      included interpersonal, work unit, and organizational safety climate dimensions.
      Others included separate measures for senior managers and frontline personnel's
      safety climate perceptions. PRINCIPAL FINDINGS: Hospitals with better safety
      climate overall had lower relative incidence of PSIs, as did hospitals with
      better scores on safety climate dimensions measuring interpersonal beliefs
      regarding shame and blame. Frontline personnel's perceptions of better safety
      climate predicted lower risk of experiencing PSIs, but senior manager perceptions
      did not. CONCLUSIONS: The results link hospital safety climate to indicators of
      potential safety events. Some aspects of safety climate are more closely related
      to safety events than others. Perceptions about safety climate among some groups,
      such as frontline staff, are more closely related than perceptions in other
      groups.

PMID- 19178584
TI  - Variation in drug prices at pharmacies: are prices higher in poorer areas?
AB  - OBJECTIVE: To determine whether retail prices for prescription drugs are higher
      in poorer areas. DATA SOURCES: The MyFloridarx.com website, which provides retail
      prescription prices at Florida pharmacies, and median ZIP code income from the
      2000 Census. STUDY DESIGN: We compared mean pharmacy prices for each of the four
      study drugs across ZIP code income groups. Pharmacies were classified as either
      chain pharmacies or independent pharmacies. DATA COLLECTION: Prices were
      downloaded in November 2006. PRINCIPAL FINDINGS: Across the four study drugs,
      mean prices were highest in the poorest ZIP codes: 9 percent above the statewide
      average. Independent pharmacies in the poorest ZIP codes charged the highest mean
      prices. CONCLUSIONS: Retail prescription prices appear to be higher in poorer ZIP
      codes of Florida.

PMID- 19178585
TI  - Method to develop health care peer groups for quality and financial comparisons
      across hospitals.
AB  - OBJECTIVE: To develop and explore the characteristics of a novel "nearest
      neighbor" methodology for creating peer groups for health care facilities. DATA
      SOURCES: Data were obtained from the Department of Veterans Affairs (VA)
      databases. STATISTICAL METHODS AND FINDINGS: Peer groups are developed by first
      calculating the multidimensional Euclidean distance between each of 133 VA
      medical centers based on 16 facility characteristics. Each medical center then
      serves as the center for its own peer group, and the nearest neighbor facilities
      in terms of Euclidean distance comprise the peer facilities. We explore the
      attributes and characteristics of the nearest neighbor peer groupings. In
      addition, we construct standard cluster analysis-derived peer groups and compare
      the characteristics of groupings from the two methodologies. CONCLUSIONS: The
      novel peer group methodology presented here results in groups where each medical
      center is at the center of its own peer group. Possible advantages over other
      peer group methodologies are that facilities are never on the "edge" of a group
      and group size-and thus group dispersion-is determined by the researcher. Peer
      groups with these characteristics may be more appealing to some researchers and
      administrators than standard cluster analysis and may thus strengthen
      organizational buy-in for financial and quality comparisons.

PMID- 19178586
TI  - Impact of public reporting on unreported quality of care.
AB  - OBJECTIVE: The impact of quality improvement incentives on nontargeted care is
      unknown and some have expressed concern that such incentives may be harmful to
      nontargeted areas of care. Our objective is to examine the effect of publicly
      reporting quality information on unreported quality of care. DATA SOURCES/STUDY
      SETTING: The nursing home Minimum Data Set from 1999 to 2005 on all postacute
      care admissions. STUDY DESIGN: We studied 13,683 skilled nursing facilities and
      examined how unreported aspects of clinical care changed in response to changes
      in reported care after public reporting was initiated by the Centers for Medicare
      and Medicaid Services on their website, Nursing Home Compare, in 2002. PRINCIPAL
      FINDINGS: We find that overall both unreported and reported care improved
      following the launch of public reporting. Improvements in unreported care were
      particularly large among facilities with high scores or that significantly
      improved on reported measures, whereas low-scoring facilities experienced no
      change or worsening of their unreported quality of care. CONCLUSIONS: Public
      reporting in the setting of postacute care had mixed effects on areas without
      public reporting, improving in high-ranking facilities, but worsening in low
      ranking facilities. While the benefits of public reporting may extend beyond
      areas that are being directly measured, these initiatives may also widen the gap
      between high- and low-quality facilities.

PMID- 19178587
TI  - Successful treatment of pulmonary metastases associated with advanced
      hepatocellular carcinoma by systemic 5-fluorouracil combined with interferon
      alpha in a hemodialysis patient.
AB  - A 54-year-old man maintained on hemodialysis had a relapse of multiple pulmonary
      metastases after multimodal therapy for primary hepatocellular carcinoma (HCC).
      He was treated with tegafur-uracil (UFT; 400 mg/day) and interferon alfa (IFN
      alpha; 5 x 10(6) units three times per week) for 4 weeks. Following this he was
      treated with systemic 5-fluorouracil (5-FU; 1000 mg/day, 5 days per week) and
      cisplatin (CDDP; 10 mg/day, 5 days per week for 2 weeks). The response to the
      above treatments was inadequate; pulmonary metastasis deteriorated. Finally, we
      selected systemic chemotherapy of 5-FU (750 mg/day, 5 days per week) and
      recombinant IFN-alpha-2b (3 x 10(6) units three times per week) for 2 weeks. This
      therapy resulted in excellent shrinkage of pulmonary metastases, without severe
      adverse reactions. Hemodialysis was performed three times a week. We report a
      case of successful treatment of pulmonary metastases by systemic combination
      chemotherapy of 5-FU-IFN, previously unsuccessfully treated with UFT-IFN and 5-FU
      CDDP in a patient on hemodialysis. Further studies are needed to select
      appropriate drugs with fluoropyrimidine-based systemic chemotherapy, and to
      analyze the pharmacokinetics of those agents in hemodialysis patients with HCC
      and extrahepatic metastases.

PMID- 19178588
TI  - What the nucleolus says to a tumour pathologist.
AB  - The importance of nucleolar changes in cancer cells is underestimated in tumour
      pathology. There is evidence that the nucleolus is the mirror of a series of
      metabolic changes that characterize cancer cells. Cell entry into the cell cycle
      is always associated with up-regulation of the nucleolar function and increased
      nucleolar size, which are also directly dependent on the rapidity of cell cycle
      progression. Furthermore, alterations of the major tumour suppressor
      retinoblastoma (Rb) and p53 pathways also contribute to the stimulation of
      nucleolar function and to nucleolar enlargement. High cell growth fraction, high
      cell growth rate and disruption of the Rb and p53 pathways are responsible for
      greater aggressiveness of cancer tissues. Therefore, the evaluation of nucleolar
      size allows one to obtain reliable information on the clinical outcome of the
      cancer: the greater the nucleolar size, the worse the tumour prognosis. Indeed, a
      series of studies carried out on numerous human tumours has shown that nucleolar
      hypertrophy (prominent nucleolus) was an independent predictive and prognostic
      parameter of a fatal clinical outcome.

PMID- 19178589
TI  - Divergent differentiation in urothelial carcinoma and other bladder cancer
      subtypes with selected mimics.
AB  - Conventional urothelial carcinoma accounts for most carcinomas of the urinary
      tract lining. However, neoplastic urothelium has the capacity to demonstrate
      enormous plasticity. A variety of unusual architectural patterns of urothelial
      carcinoma, such as the nested, microcystic and inverted variants, can be mistaken
      for reactive processes or benign tumours. Others such as the micropapillary,
      plasmacytoid and discohesive variants, can mimic metastatic tumour from other
      sites. The micropapillary variant in particular is more aggressive. In addition,
      urothelial carcinoma has a propensity to demonstrate divergent differentiation
      with glandular, squamous, small cell neuroendocrine, lymphoepithelioma-like,
      sarcomatoid or other elements. Pure squamous carcinoma or adenocarcinoma (the
      latter in particular) can be difficult to distinguish from contiguous or
      metastatic spread. Some variants have prognostic and potential therapeutic
      implications. Molecular genetic evidence has emerged recently supporting a close
      relationship between urothelial carcinoma and various divergent elements.
      Sarcomatoid carcinoma and its differential diagnosis with other spindle cell
      lesions of urinary tract will be covered in a separate review.

PMID- 19178590
TI  - Correction of facial lipoatrophy using autologous fat transplants in HIV-infected
      adolescents.
AB  - OBJECTIVES: Antiretroviral therapy has dramatically improved the survival of HIV
      infected children. Nevertheless, side effects comparable to those found in adults
      have been encountered, such as facial lipoatrophy, which can have a negative
      impact on the self-esteem of otherwise healthy adolescents. Cosmetic surgical
      procedures in adolescents raise psychological issues which need to be
      specifically addressed and which have never been previously reported in this
      population. We evaluated the patient satisfaction, safety and cosmetic results of
      HIV-infected adolescents who experienced autologous fat transplants for the
      correction of facial lipoatrophy. METHODS: We report the results of plastic
      surgery using autologous fat transplants (Coleman's Lipostructure) in six HIV
      infected adolescents with facial lipoatrophy: three boys and three girls, aged 14
      19 years. RESULTS: The quantity of reinjected fat on each side of the face varied
      from 5 to 12 mL within a single procedure. All the patients reported being
      satisfied or very satisfied with the cosmetic results and reported a positive
      impact on their daily life. CONCLUSIONS: With well-trained surgeons and carefully
      selected indications, corrective surgery of facial lipoatrophy in HIV-infected
      adolescents can provide immediate and long-lasting benefits in terms of physical
      appearance and psychological wellbeing, and should be considered as a component
      of comprehensive care.

PMID- 19178591
TI  - How does loss to follow-up influence cohort findings on HIV infection? A joint
      analysis of the French hospital database on HIV, Mortalite 2000 survey and death
      certificates.
AB  - OBJECTIVE: We aimed to retrieve the vital status of patients lost to follow-up
      (LFU), with no further visits for at least 12 months, for the 34,835 patients in
      the Agence Nationale de Recherche sur le SIDA CO4 French Hospital Database on HIV
      (ANRS CO4 FHDH) seen in 1999 and to examine how loss to follow-up might influence
      estimates of survival and the impact of delayed access to care (DAC) on survival.
      METHODS: The status of LFU patients was established by using the mid-2006 update
      of the FHDH in which their status 12 months after loss to follow-up was added
      when available and by matching with the Mortalite 2000-Epidemiological Centre for
      Medical Causes of Death (CepiDc) database, which included HIV-infected patients
      dying in 2000. We compared Kaplan-Meier and hazard ratio (HR) estimates before
      and after correction for the status of LFU patients. RESULTS: In the mid-2006
      updated FHDH, of the patients seen in 1999, 7.5% were LFU: of these, 2.1% later
      returned for follow-up, with a median time without follow-up in an FHDH centre of
      3.5 years, and 5.4% had no further FHDH visits whatsoever, of whom 29.8% died
      according to Mortalite 2000-CepiDc. After correction, the estimated 1-year
      survival rates following enrolment in 1999 differed between the original and
      updated analyses (97.1 vs. 95.9%, respectively; P=0.017); the estimates of
      mortality HRs associated with DAC did not differ during the first 6 months, but
      did differ for the 6-18-month period. CONCLUSIONS: Among LFU patients, 28.1%
      returned to follow-up after several years and at least 21.4% died, which led to a
      slight overestimation of both survival and the impact of DAC on survival.

PMID- 19178592
TI  - Prolonged use of tenofovir in HIV/hepatitis B virus (HBV)-coinfected individuals
      does not lead to HBV polymerase mutations and is associated with persistence of
      lamivudine HBV polymerase mutations.
AB  - OBJECTIVES: The aim of the study was to identify and characterize hepatitis B
      virus (HBV) polymerase gene mutations associated with ongoing HBV replication in
      HIV/HBV-coinfected individuals receiving tenofovir (TDF). METHODS: This
      retrospective cross-sectional study identified 28 HIV/HBV-coinfected individuals
      who had received TDF for at least 3 months. All patients had samples available
      while receiving TDF (on-TDF), and 24 also had samples available prior to
      treatment (pre-TDF). Case records were reviewed to obtain clinical and
      virological data at the times of sampling (+/-3 months). The HBV DNA of all
      samples was amplified using polymerase chain reaction (PCR), and the polymerase
      region of PCR-positive samples was sequenced and compared with reference HBV
      data. RESULTS: Of the pre-TDF samples, 15 of 24 (63%) were HBV PCR positive. Of
      the on-TDF samples, four of 28 (14%) were HBV PCR positive (mean time on TDF 13.5
      months; range 3-23 months). Lamivudine (3TC)-resistance mutations were detected
      in three of four (75%) of these viraemic samples. The previously identified
      putative TDF-resistance mutations, rtA194T+rtL180M+rtM204V, were not detected in
      any individual. CONCLUSIONS: Unique mutations in the HBV polymerase gene
      associated with TDF resistance are rare in HIV/HBV coinfection. 3TC-resistance
      mutations persist and a significant proportion of patients are HBV PCR positive
      despite the addition of TDF.

PMID- 19178593
TI  - Epigenetics and T helper 1 differentiation.
AB  - Naive T helper cells differentiate into two subsets, T helper 1 and 2, which
      either transcribe the Ifng gene and silence the Il4 gene or transcribe the Il4
      gene and silence the Ifng gene, respectively. This process is an essential
      feature of the adaptive immune response to a pathogen and the development of long
      lasting immunity. The 'histone code' hypothesis proposes that formation of stable
      epigenetic histone marks at a gene locus that activate or repress transcription
      is essential for cell fate determinations, such as T helper 1/T helper 2 cell
      fate decisions. Activation and silencing of the Ifng gene are achieved through
      the creation of stable epigenetic histone marks spanning a region of genomic DNA
      over 20 times greater than the gene itself. Key transcription factors that drive
      the T helper 1 lineage decision, signal transducer and activator 4 (STAT4) and T
      box expressed in T cells (T-bet), play direct roles in the formation of
      activating histone marks at the Ifng locus. Conversely, STAT6 and GATA binding
      protein 3, transcription factors essential for the T helper 2 cell lineage
      decision, establish repressive histone marks at the Ifng locus. Functional
      studies demonstrate that multiple genomic elements up to 50 kilobases from Ifng
      play critical roles in its proper transcriptional regulation. Studies of three
      dimensional chromatin conformation indicate that these distal regulatory elements
      may loop towards Ifng to regulate its transcription. We speculate that these
      complex mechanisms have evolved to tightly control levels of interferon-gamma
      production, given that too little or too much production would be very
      deleterious to the host.

PMID- 19178595
TI  - Persistent apical periodontitis associated with a calcifying odontogenic cyst.
AB  - AIM: To report a case of calcifying odontogenic cyst (COC) that was suggestive of
      apical periodontitis adjacent to the roots of the maxillary incisor teeth.
      SUMMARY: Tooth 21 presented with clinical and radiographic signs of secondary
      infection, a post within the root canal and substantial internal tooth
      destruction; it was scheduled for endodontic surgery. Teeth 12 and 22 were root
      filled following the placement of a calcium hydroxide intracanal dressing for 21
      days. Three attempts at root canal disinfection in tooth 11 were unsuccessful,
      and a persistent purulent drainage precluded completion of root canal treatment.
      Surgical enucleation of the periapical lesion was undertaken and the tissues
      submitted for histopathological examination. A diagnosis of COC was established
      based on the microscopic analysis. COC is an unusual benign lesion that
      represents 2% of all odontogenic lesions. Depending on the stage of development,
      it can mimic a large lesion associated with apical periodontitis and should
      therefore be considered in the differential diagnosis. In the case of COC, the
      definitive diagnosis can only be made with histopathological analysis. KEY
      LEARNING POINTS: Persistent apical periodontitis may be of nonendodontic origin.
      * Histological examination is essential to establish the cause of persistent
      apical periodontitis. * Calcifying odontogenic cyst can mimic apical
      periodontitis.

PMID- 19178594
TI  - 1alpha,25-dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by
      Mycobacterium tuberculosis infection.
AB  - Matrix metalloproteinases (MMP) can degrade all components of pulmonary
      extracellular matrix. Mycobacterium tuberculosis induces production of a number
      of these enzymes by human macrophages, and these are implicated in the
      pathogenesis of pulmonary cavitation in tuberculosis. The active metabolite of
      vitamin D, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], has previously
      been reported to inhibit secretion of MMP-9 in human monocytes (MN), but its
      influence on the secretion and gene expression of MMP and tissue inhibitors of
      MMP (TIMP) in M. tuberculosis-infected cells has not previously been
      investigated. We therefore determined the effects of 1alpha,25(OH)(2)D(3) on
      expression, secretion and activity of a number of MMP and TIMP in M. tuberculosis
      infected human leucocytes; we also investigated the effect of
      1alpha,25(OH)(2)D(3) on the secretion of interleukin-10 (IL-10) and prostaglandin
      E(2) (PGE(2)), both transcriptional regulators of MMP expression. We found that
      M. tuberculosis induced expression of MMP-1, MMP-7 and MMP-10 in MN and MMP-1 and
      MMP-10 in peripheral blood mononuclear cells (PBMC). 1alpha,25(OH)(2)D(3)
      significantly attenuated M. tuberculosis-induced increases in expression of MMP-7
      and MMP-10, and suppressed secretion of MMP-7 by M. tuberculosis-infected PBMC.
      MMP-9 gene expression, secretion and activity were significantly inhibited by
      1alpha,25(OH)(2)D(3) irrespective of infection. In contrast, the effects of
      1alpha,25(OH)(2)D(3) on the expression of TIMP-1, TIMP-2 and TIMP-3 and secretion
      of TIMP-1 and TIMP-2 were small and variable. 1alpha,25(OH)(2)D(3) also induced
      secretion of IL-10 and PGE(2) from M. tuberculosis-infected PBMC. These findings
      represent a novel immunomodulatory role for 1alpha,25(OH)(2)D(3) in M.
      tuberculosis infection.

PMID- 19178596
TI  - Sperm DNA integrity in cancer patients: the effect of disease and treatment.
AB  - As oncological treatment might impair the patients' fertility, male cancer
      patients are offered to cryopreserve semen prior to treatment. Impaired sperm DNA
      quality is associated with reduced fertility, and in case of assisted
      reproduction, sperm DNA integrity may have an impact on choice of method.
      Therefore, we have assessed sperm DNA integrity in cancer patients, comparing pre
      and post-treatment quality. Sperm DNA integrity was investigated in
      cryopreserved semen from 121 cancer patients, the predominating diagnoses were
      germ cell cancer (GCC) and Hodgkin's lymphoma (HL). Post-treatment samples, with
      a median follow-up of 3 years, were analysed for 58 of the men, allowing a pre-
      and post-treatment analysis on an individual basis. Sperm DNA integrity was
      assessed using the Sperm Chromatin Structure Assay and expressed here as the DNA
      Fragmentation Index (DFI%). One hundred and thirty-seven fertile men served as
      controls. Before treatment, GCC (n = 84) and HL (n = 18) patients had higher DFI%
      than controls (n = 143) with a mean difference of 7.7 (95% CI 3.2-8.8) and 7.0
      (95% CI 2-12), respectively. The same trend was observed for other cancer
      diagnoses, but without reaching statistical significance (mean difference 3.6,
      95% CI -1.2 to 8.4). No increase was seen in DFI% comparing pre- and post
      treatment semen, regardless of treatment modality. A moderate elevation of DFI%
      was observed in cryopreserved semen from cancer patients. Oncological treatment,
      generally, did not induce any increase in DFI. These findings should be
      considered when discussing the utilization of pre-treatment cryopreserved semen
      vs. post-treatment fresh sperm in cancer patients undergoing assisted
      reproduction.

PMID- 19178597
TI  - Aprotinin in severe acute pancreatitis.
AB  - Aprotinin, a Kunitz protease inhibitor, has a wide inhibitory action with
      particular activity against trypsin, chymotrypsin and kallikrein, making it
      theoretically attractive in ameliorating the effects of acute pancreatitis. Its
      use in acute pancreatitis has been studied for the last 50 years with
      disappointing results. In this paper, we review the previous studies and argue
      that all the studies have not been adequately powered, have inappropriate end
      points, but most importantly have not attained adequate plasma and peritoneal
      levels of aprotinin to produce sufficient inhibitory activity. We hypothesise
      that a well-powered study with adequate aprotinin dosing may clarify its clinical
      benefit in severe acute pancreatitis.

PMID- 19178598
TI  - The evolving epidemiology of pulmonary arterial hypertension.

PMID- 19178599
TI  - Pulmonary hypertension in chronic heart failure.
AB  - The presence of PH in patients who suffer from CHF is common and predicts a poor
      outcome. However, precise definitions for PH associated with left heart disease,
      or 'out-of-proportion' PH as well as standardised vasodilator testing protocols
      are lacking. Moreover, apart from single-centre observations no large-scale trial
      to date has demonstrated a long-term benefit from pulmonary vasoactive drugs. As
      a result, there are currently no consensus recommendations for the treatment of
      PH in the presence of CHF. Off-label use of specific vasodilators in this patient
      population is discouraged. In a majority of cases, treatment of the underlying
      left heart disease leads to a decrease in pulmonary pressures. In light of novel
      agents to treat PH, trials that specifically address 'out-of-proportion' PH in
      CHF patients are warranted.

PMID- 19178600
TI  - What we know and what we would like to know about genetics and pulmonary arterial
      hypertension.
AB  - Research on the molecular basis of PAH caused by BMPR-II mutations is beginning
      to yield novel approaches to therapy, for example, small molecule inhibitors of
      ALK-5. Enhancement of BMP signalling may be possible with BMP-derived ligands or
      rescue of BMPR-II cell surface expression for some mutations. For mutations
      leading to nonsense mediated mRNA decay, approaches aimed at transcript
      stabilisation provide another possible intervention. To further our genetic
      understanding of this rare disease, large international collaborative studies are
      needed to generate the numbers of patients necessary to undertake meaningful
      genome wide association studies for novel susceptibility genes or disease
      modifying genes. In addition, to provide accurate information to families,
      longitudinal cohort studies, coupled with biomarker studies, are required of
      affected and unaffected individuals in families segregating BMPR-II mutations.

PMID- 19178601
TI  - The search for an oral prostanoid to treat pulmonary arterial hypertension
      continues. Are we getting any closer?
AB  - Among the most commonly used therapies to treat pulmonary arterial hypertension
      (PAH) are the prostanoids. Epoprostenol, a relatively effective therapy for PAH,
      has its limitations, which are largely attributable to its pharmacokinetic
      properties and its requirement for intravenous administration. The development of
      an equally effective oral prostanoid would be an important advance in the PAH
      armamentarium. An early generation oral prostanoid, beraprost, was previously
      demonstrated to have modest, transient clinical benefits, but at the cost of a
      high proportion of intolerable side effects. TRK-100STP is a newer generation
      oral prostanoid currently under clinical investigation.

PMID- 19178602
TI  - HIV-associated pulmonary arterial hypertension: a clinical problem that is here
      to stay?
AB  - HIV-associated pulmonary arterial hypertension (PAH) is a serious complication of
      HIV infection and associated with high patient mortality. There are multiple
      similarities between HIV-associated PAH and idiopathic PAH and standard PAH
      medications have been used to treat the condition with reported success. Prior to
      the advent of highly active antiretroviral treatments (HAART), the prevalence of
      the condition in the HIV-infected population was estimated at 0.5%. In a recently
      published, large, prospective, multi-centre study performed in the HIV-population
      across France, the prevalence of HIV-associated PAH was estimated at 0.46%. In
      this article, we provide an overview of HIV-associated PAH and summarise the
      methodology, pertinent findings and implications of this important paper.

PMID- 19178603
TI  - Glial choristoma of the tongue: report of a case and clinico-pathological
      features.

PMID- 19178604
TI  - Radiographic assessment of dental anomalies in patients with ectopic maxillary
      canines.
AB  - BACKGROUND: The aetiology of palatally and labially located ectopic maxillary
      canines is multifactorial. Accordingly, early prediction of this eruptional
      disturbance is in most cases not possible. AIM: The purpose of this study was to
      analyse dental deviations in cases with either palatal or labial ectopic canines.
      DESIGN: Panoramic and intra-oral radiographs from 50 patients with palatally
      located (38 females and 12 males) and 19 patients with labially located ectopic
      canines (11 females and 8 males), aged 10 years, 2 months-18 years, 1 month, were
      analysed. Dental deviations registered were crown and root malformations,
      agenesis, and eruption deviations. Registrations were performed in the maxillary
      incisor field and in the dentition in general. RESULTS: The study documented that
      palatally as well as labially located ectopic canines can occur in dentitions
      without other dental deviations. Dental deviations occurred in approximately two
      thirds of all cases, more often in females and in cases with palatally located
      canines. More than half of the females with palatally located canines had
      deviations in the maxillary incisors and in the dentition in general. CONCLUSION:
      Dental deviations may be considered a risk factor for maxillary canine ectopia.
      Early identification of patients at risk and appropriate interceptive treatment
      may reduce ectopic eruption of maxillary canines.

PMID- 19178605
TI  - Dental anxiety among survivors of childhood cancer: a cross-sectional study.
AB  - BACKGROUND: Childhood cancer survivors may have experienced a high number of
      invasive medical and dental procedures which are known to be risk factors for
      dental anxiety. AIM: The aim of this study was to examine the prevalence of
      dental anxiety among children who have survived cancer. DESIGN: In a cross
      sectional study, we examined 51 6- to 14-year-old children who had been treated
      for cancer at Aalborg Hospital, and 192 children without cancer. All children
      answered the Dental Subscale of the Children's Fear Survey Schedule. Dental
      anxiety was defined as a dental anxiety score exceeding the mean dental anxiety
      score + 1 standard deviation for the children without cancer. RESULTS: Children
      with cancer did not have an increased prevalence of dental anxiety compared with
      children without cancer: the prevalence ratio was 0.41 [95% confidence interval
      (CI): 0.10-1.24]. The mean dental anxiety score was 23.1 (95% CI: 21.2-25.0)
      among children who had been treated for cancer, and 24.7 (95% CI: 23.4-26.0)
      among children without cancer (mean difference: 1.6; 95% CI: 1.1-4.3).
      CONCLUSION: Cancer and cancer treatment during childhood were not associated with
      an increased risk of dental anxiety in this population.

PMID- 19178606
TI  - Strategies for caries risk assessment in children and adolescents at public
      dental clinics in a Swedish county.
AB  - BACKGROUND: Since caries prevalence has decreased and become polarized, high-risk
      preventive strategies have been widely adopted. The underlying factors leading to
      assessment and management of caries risk are poorly understood. AIM: The aim of
      this study was to identify the factors forming the basis for dentist's caries
      risk assessment in dental care for children and adolescents. DESIGN: From all
      3372 children in a Swedish county identified as at high risk for developing
      caries, a sample of dental records from 432 children, aged 3-19 years, were
      randomly selected to be analysed in the study. Information about medical and
      social history, dental status, dietary habits, oral hygiene, and salivary data
      was obtained from the records. RESULTS: The results show that the only data
      registered in the majority of the dental records were dental status from the
      clinical examination and bitewing radiographs. In approximately half of the
      dental records, medical history and data concerning oral hygiene were registered.
      Dental history and dietary habits were noted in approximately 25% of the dental
      records, whereas other risk factors/indicators were occasionally registered.
      CONCLUSIONS: Dentists mainly base their caries risk assessments on past caries
      experience, a reliable risk indicator for assessing the risk of being affected by
      caries again. In children with no experience of caries, knowledge of other risk
      factors/indicators needs to be available to perform a caries risk assessment. In
      this study, documentation of such knowledge was strongly limited.

PMID- 19178607
TI  - Non-gelatinized starch influences the deposition of n-3 fatty acids in the muscle
      of a tropical freshwater fish, Labeo rohita.
AB  - A 60-day feeding trial was conducted to study the influence of gelatinized (G) to
      non-gelatinized (NG) starch ratio in the diet on fatty acids profiles and
      oxidative status in Labeo rohita fingerlings. Two hundred and thirty-four
      fingerlings (average weight: 2.53 g) were distributed in six treatment groups
      with each of three replicates. Six semi-purified diets either containing NG
      and/or G corn starch (42.43%) viz., T(1) (100% NG and 0% G starch), T(2) (80% NG
      and 20% G starch), T(3) (60% NG and 40% G starch), T(4) (40% NG and 60% G
      starch), T(5) (20% NG and 80% G starch) and T(6) (0% NG and 100% G starch) was
      fed to respective groups. Catalase, superoxide dismutase and malic enzyme
      activities decreased linearly with the increasing level of G starch, whereas
      reverse trend was found for glucose-6-phosphate dehydrogenase. Total saturated
      fatty acids in muscle increased with the increasing level of G starch in the
      diet. Total n-3 fatty acids decreased linearly with the increasing level of G
      starch in the diet. Among the n-3 fatty acids, linolenic acids content was more
      in NG starch fed group. Similarly, eicosapentaenoic acid contents gradually
      decreased with increasing level of G starch content. The n-6/n-3 ratio was higher
      in G starch fed group. This suggests that dietary starch type may be manipulated
      for quality improvement of fish flesh.

PMID- 19178608
TI  - Effects of zinc levels on activities of gastrointestinal enzymes in growing rats.
AB  - The present study investigated the effect of different zinc (Zn) levels on
      activities of gastrointestinal digestive enzymes of growing rats. Four diets
      including Zn-adequate (ZA; 46 mg/kg, control), Zn-deficient (ZD; 3 mg/kg), high
      Zn supply (ZH; 234 mg/kg) and pair-fed in which animals received the ZA diet at
      restricted amounts reflecting feed intake of the ZD group were fed to rats for 5
      weeks. Dietary Zn was supplemented with ZnO. The results showed that Zn
      deficiency resulted in decreases in body weight, while ZH supply stimulated
      growth. The activities of sucrase, lactase and lipase were unaffected by dietary
      Zn levels. Maltase activity, however, was reduced in ZD group and elevated in ZH
      group. Amylase and protease activities were depressed by zinc deficiency.
      However, rats fed the Zn-repletion diet displayed higher activity of pepsin,
      pancreatic amylase and protease. In particular, ZH supply did have no effect on
      intestinal hydrolases activities. The present study suggested that zinc
      deficiency impaired the activities of digestive enzymes and growth of animals.
      However, ZH supply might improve the digestion of nutrients via increasing
      activities of gastrointestinal hydrolase and probably enhanced animal health.

PMID- 19178609
TI  - No easy solution for the fractionation of faecal nitrogen in captive wild
      herbivores: results of a pilot study.
AB  - Faecal nitrogen (FN) concentration is used as a marker for habitat quality and
      digestive efficiency in free-ranging herbivores. In herbivores, FN can be
      separated into undigested plant N (analysed as the N concentration of the neutral
      detergent residue) and metabolic faecal N (MFN). It has been suggested that by
      differential analysis of the faecal fibre-bound N, the MFN fraction can be
      further split into a bacterial N and an endogenous N fraction [Hesta et al., Br.
      J. Nutr. 90 (2003) 1007]. We applied these methods to 96 faecal samples of 48
      mammalian herbivore species from zoos. Species were grouped into coprophageous
      and non-coprophageous hindgut fermenters and ruminating and non-ruminating
      foregut fermenters. Diet was not controlled. The FN decreased with body mass,
      possibly reflecting higher proportions of concentrates in diets of smaller
      animals. The proportion of MFN increased with FN, indicating that higher quality
      food might enhance the gastrointestinal bacterial flora. The only outlier to this
      pattern was the lesser panda (Ailurus fulgens), confirming the low relevance of
      fermentative digestion in this herbivorous 'carnivore'. No relevant differences
      between the four digestion types were noted. The proportion of endogenous faecal
      N (32-80% of FN) was always higher than that of bacterial faecal N (7-30%), which
      contradicts basal understanding of herbivore digestive physiology. Thus, the
      method of Hesta et al. (2003) does not appear applicable to herbivores. While the
      results do not exclude the possibility that detailed differences might occur
      between digestion types, they indicate a high degree of similarity between
      herbivores that rely on bacterial fermentation, regardless of their digestion
      type, with respect to metabolic faecal losses.

PMID- 19178610
TI  - Preserved pleural integrity provides better respiratory function and pain score
      after coronary surgery.
AB  - BACKGROUND AND AIM: Patients undergoing surgical procedures through median
      sternotomy have reduced pulmonary function in the postoperative period. Our study
      was designed to evaluate the effect of pleural integrity in terms of respiratory
      functions and pain score after coronary bypass procedures. METHODS: In a
      randomized, prospective study we evaluated 320 patients in two groups. Group I (n
      = 160) patients were the patients whose pleural cavity was intact while internal
      mammary artery (IMA) harvesting, and in group II (n = 160) the pleural cavity of
      the patients was opened. They matched in terms of postoperative respiratory
      functions and pain score. RESULTS: FEV1 (%) and FEV1/FVC levels at the
      postoperative fifth day were significantly lower in group II (I = 71.5 +/- 4.9
      vs. II = 63.5 +/- 8.3 and I = 24.1 vs. II = 22.1), respectively (p < 0.05). The
      rate of postoperative pleural effusions and atelectasis at the postoperative
      fifth day were significantly higher in group II (I = 35%, 15% vs. II = 48%, 35%),
      respectively (p < 0.05). The pain score was higher in group II at postoperative
      fifth day. CONCLUSIONS: All patients undergoing cardiac surgery suffer
      deterioration in pulmonary functions. Pleurotomy seems to compound this with
      increased rates of atelectasis and pleural effusions. Moreover, preserving
      pleural integrity provides beneficial effects on pain score after coronary
      operations especially in the early postoperative period.

PMID- 19178611
TI  - Endovascular repair of the descending thoracic aorta for penetrating
      atherosclerotic ulcer disease.
AB  - The pathological variants of acute aortic syndromes include classic dissection,
      intramural hematomas, and penetrating atherosclerotic ulcers (PAUs). The subject
      of the appropriate management and treatment of PAUs continues to expand as this
      disease entity is increasingly identified. The application of thoracic
      endografting, or thoracic endovascular aortic repair (TEVAR), to treat these
      acute aortic pathologies is clearly evolving and the ultimate effectiveness and
      durability of thoracic endografting remains to be determined as clinical
      experience increases. The disease pathology of PAUs and the use of endovascular
      stent graft placement in PAU disease are closely examined in this manuscript.

PMID- 19178612
TI  - Perforating folliculitis, angioedema, hand-foot syndrome--multiple cutaneous side
      effects in a patient treated with sorafenib.
AB  - A patient with clear cell renal cell carcinoma was treated with sorafenib, a
      multikinase inhibitor, which induced a variety of cutaneous side effects. In
      addition to xerosis, he developed angioedema (AE), hand-foot syndrome (HFS) and
      perforating folliculitis (PF). The latter three occurred in a dose-dependent
      manner. AE was observed at the recommended daily dose of 800 mg. Dose reduction
      to 400 mg prevented its recurrence. At this dose level, the patient exhibited
      HFS, which cleared upon further reduction of the dose. While receiving 200 mg,
      the patient developed PF. To the best of our knowledge, this is the first
      description of a case of PF during treatment with sorafenib.

PMID- 19178613
TI  - Erythema multiforme majus (Fuchs syndrome) associated with Mycoplasma pneumoniae
      infection in two patients.
AB  - In Germany Fuchs syndrome is used to describe a variant of erythema multiforme
      majus which mainly involves the mucosal surfaces. As the skin may be completely
      unaffected, it is an under-recognized diagnosis and often difficult to confirm.
      Clinical features involve erythema, erosions and ulcerations of the oral mucosa.
      In most cases there is severe conjunctivitis and sometimes the genital mucosa is
      involved. Most cases of Fuchs syndrome are triggered by infections; herpes
      simplex virus and Mycoplasma pneumoniae are the most common causes. We describe
      two women presenting with Fuchs syndrome after respiratory illness caused by
      Mycoplasma pneumoniae.

PMID- 19178614
TI  - Unique epidermolytic bullous dermatosis with associated lethal cardiomyopathy
      related to novel desmoplakin mutations.
AB  - BACKGROUND: Desmoplakin plays a vital role in cell adhesion, linking the
      transmembrane desmosomal complex to the cytoskeletal network. Clues to the
      biological significance of desmoplakin have emerged from the embryonic lethal
      phenotype of null mice and from naturally occurring human desmoplakin mutations,
      which cause cardiocutaneous phenotypes. INDEX CASE: In this study, we describe a
      child who presented with the unique constellation of bullous dermatosis, profound
      plantar keratoderma, alopecia totalis and cardiomyopathy leading to sudden
      cardiac death at the age of 9 years. RESULTS: This complex cardiocutaneous
      phenotype is associated with compound heterozygosity for two novel nonsense
      desmoplakin mutations. Histological examination of a plantar skin biopsy showed
      full thickness epidermal acantholysis with superimposed spongiosis,
      hyperorthokeratosis and focal parakeratosis. Immunohistochemistry and
      quantitative confocal microscopy showed abnormal tissue distribution and reduced
      levels of expression for plakoglobin, desmoplakin and connexin 43 at epidermal
      junctional sites. CONCLUSIONS: Interpretation of the changes in the context of
      the two mutations provides insight into the mechanism of clinical cell adhesion
      disease.

PMID- 19178615
TI  - Multiple clear cell trichoblastoma.
AB  - Clear cell trichoblastoma is a very rare neoplasm with follicular differentiation
      described recently. Only three cases of clear cell trichoblastoma were reported
      in literature and all of them were presented as single lesion. Here, we report a
      case of clear cell trichoblastoma with multiple lesions in a child. Two biopsies
      from the patient showed that the neoplasm was located in the dermis, and step
      sections showed that they were connected with the follicular infundibulum. The
      neoplasm was almost made of clear cells that had clear cytoplasm and
      eccentrically disposed nucleus. At the periphery of the neoplasm, the clear cells
      showed palisade array with the nucleus at the pole opposite the thick basement
      membrane, and only a few basal cells were located at the periphery of the
      neoplasm. Periodic acid-Schiff stain was almost negative in the clear cells.
      Immunohistochemistry studies showed the neoplasm stained positive for AE1/AE3 but
      negative for CAM 5.2, cytokeratin 7, cytokeratin 20, epithelia antigen,
      carcinoembryonic antigen, epithelial membrane antigen, androgen receptor, S-100
      and CD34. The clinical and histopathological characters suggested the diagnosis
      of multiple clear cell trichoblastoma. After 20 months' follow up, the lesions of
      the patient showed incomplete regression, which is a rare phenomenon in neoplasm
      with follicular differentiation.

PMID- 19178616
TI  - Contextual variables affecting aggressive behaviour in individuals with mild to
      borderline intellectual disabilities who live in a residential facility.
AB  - BACKGROUND: Aggression is a common type of problem behaviour in clients with mild
      to borderline intellectual disability who live in a residential facility. We
      explored contextual events that elicit aggressive behaviour and variables that
      were associated with such events. METHOD: Respondents were 87 direct-care staff
      members of 87 clients with aggressive behaviour who lived in a residential
      facility. Staff members completed the Contextual Assessment Inventory (CAI) and a
      questionnaire on demographic information and types, frequency and severity of
      aggressive behaviour. Internal consistency of the total CAI was excellent (alpha
      = 0.95), and Cronbach alpha's for the CAI sub-scales ranged from 0.75 to 0.93.
      Inter-rater agreement for the CAI could be considered good (mean intra-class
      correlation coefficient = 0.63). RESULTS: Both social and task-related events
      were reported to evoke aggressive behaviour of clients most often. Negative
      interactions, task characteristics and daily routines relatively often evoked
      aggressive behaviour while an uncomfortable environment, medication, illness and
      physiological states (i.e. physical and biological events) evoked aggressive
      behaviour least often. Mean CAI sub-scale scores were significantly related to
      gender, IQ and frequency of aggressive behaviour. CONCLUSION: The present study
      extends our knowledge regarding events that are associated with an increased
      probability of aggressive behaviour. Knowledge of these contextual variables may
      be helpful in designing programmes (e.g. applied behaviour analysis, social
      skills training and cognitive behavioural therapies) for the management and
      prevention of aggressive behaviour in clients with mild to borderline
      intellectual disability who live in a residential facility.

PMID- 19178617
TI  - Adults with intellectual disabilities: prevalence, incidence and remission of
      aggressive behaviour and related factors.
AB  - INTRODUCTION: Aggressive behaviours can be disabling for adults with intellectual
      disabilities (ID), with negative consequences for the adult, their family and
      paid carers. It is surprising how little research has been conducted into the
      epidemiology of these needs, given the impact they can have. This study
      investigates point prevalence, 2-year incidence and 2-year remission rates for
      aggressive behaviour (physically aggressive, destructive and verbally
      aggressive), and it investigates which factors are independently associated with
      aggressive behaviour. METHODS: All adults with ID - within a geographically
      defined area of Scotland, UK - were recruited to a longitudinal cohort. At
      baseline, assessments were undertaken of demography, lifestyle, supports,
      development, problem behaviours, disabilities and physical and mental health.
      These were repeated for a 2-year period. RESULTS: At baseline, the participation
      rate was 1023 (65.5%). After 2 years, the cohort retention was 651 adults. The
      point prevalence of Diagnostic Criteria for Psychiatric Disorders for Use with
      Adults with Learning Disabilities/Mental Retardation (DC-LD) aggressive behaviour
      was 9.8% (95% confidence interval = 8.0-11.8%), 2-year incidence was 1.8%, and 2
      year remission rate from all types of aggressive behaviour meeting DC-LD criteria
      was 27.7%. The factors independently associated with aggressive behaviours were
      lower ability, female gender, not living with a family carer, not having Down
      syndrome, having attention-deficit hyperactivity disorder and having urinary
      incontinence. Incidence of aggressive behaviour meeting DC-LD criteria in adult
      life is similar to that for each of psychotic, anxiety and organic disorders.
      CONCLUSIONS: Aggressive behaviour is common among adults with ID, but contrary to
      previous suggestions, more than a quarter remit within the short to medium term.
      This is important knowledge for professionals as well as the person and her/his
      family and paid carers. There is much yet to learn about the mechanisms
      underpinning aetiology and maintenance of aggressive behaviour in this
      population, and exploratory epidemiological investigations such as this have a
      role to play in progressing research towards further hypothesis testing and
      trials to influence clinical practice, service development and policy.

PMID- 19178618
TI  - Surgical stent fabrication for unilateral nasal obstruction of the anterior
      portion of the nasal airway.
AB  - A description is given of the indication and technical steps for fabricating a
      unilateral nasal stent to maintain patency of the nasal passage after surgical
      opening of an obstruction in a pediatric case. The methodology uses a two-step
      impression of the contralateral unobstructed naris and exterior valve region to
      generate a two-piece injection mold. The mold is used to fabricate a soft
      silicone-based anatomical stent. It supports an intranasal skin graft that was
      placed to reduce the risk of granulation.

PMID- 19178619
TI  - Comparison of marginal fit between all-porcelain margin versus alumina-supported
      margin on Procera Alumina crowns.
AB  - PURPOSE: Procera Alumina crowns are widely used; however, the effect of crown
      margin design on marginal fit is unknown. This study measured and compared the
      precision of fit of Procera Alumina crowns with two crown margin designs: all
      porcelain versus alumina-supported margins. MATERIALS AND METHODS: Sixteen
      noncarious extracted human premolars were prepared for Procera((R)) Alumina
      crowns with an internally rounded shoulder preparation. Impressions were made
      from all teeth, and master dies were poured with type IV dental stone. The
      specimens were randomly divided into two groups. Procera Alumina crowns were
      fabricated: eight crowns with circumferential porcelain-butt (all-porcelain)
      margins and eight crowns with coping (alumina-supported) margins (control).
      Precision of fit was measured at six points on each crown with a profilometer
      (profile projector). The data were statistically analyzed with an independent
      samples t-test (alpha < 0.05). RESULTS: The mean marginal gap size (microm) of
      coping margins was 68.07 +/- 16.08 and of porcelain-butt margins was 101.29 +/-
      43.71. There was no statistically significant difference (p= 0.065) of the
      marginal gap size between coping margins and porcelain-butt margins. CONCLUSION:
      The results of this study demonstrate that there was no statistically significant
      difference in the marginal fit of coping and porcelain-butt margins. Both margin
      designs are within clinically acceptable ranges. Therefore, clinicians may choose
      to use a coping margin, as it is less labor intensive and requires less time for
      fabrication, unless there is a specific high esthetic need for a porcelain-butt
      margin.

PMID- 19178621
TI  - Who is teaching undergraduate prosthodontics in US dental schools, 2007?
AB  - PURPOSE: The shortage of full-time dental school faculty along with a slow steady
      increase in student enrollment is not a new phenomenon. The purpose of this study
      was to determine who is teaching undergraduate prosthodontics in US dental
      schools-what percent are full-time faculty; what percent are prosthodontists; and
      what percent are board-certified prosthodontists-to allow schools to make a real
      time comparison of the composition of instructors they have teaching
      prosthodontics to the apparent status quo. MATERIALS AND METHODS: A short, ten
      question survey was sent via e-mail to representatives at the 55 undergraduate US
      dental schools. A cover letter explained the nature of the study and requested
      participation and electronic return of the survey. Three weeks after the initial
      request, an aggressive follow-up was conducted to schools that had not returned
      the survey. Answers were converted to percentages to compensate for differences
      between schools with many or few instructors. Schools were also grouped by
      location to see if regional differences exist. RESULTS: Thirty-eight (69%) of the
      surveys were completed and returned. In general, the division between full-time
      and part-time instructors is about 50%. More removable prosthodontic instructors
      (60%) than fixed instructors (44%) are prosthodontists, and only a small
      percentage of the total (18% removable and 15% fixed) have completed board
      certification. The South and Midwest had the highest percentage of
      prosthodontists involved in teaching; the South had the highest percentage with
      specialty board certification. CONCLUSION: This study indicated that only a few
      schools are fortunate enough to have sufficient full-time, specialty-trained
      faculty available for complete coverage of all undergraduate prosthodontic
      courses and clinics. The information presented serves as a baseline for future
      comparison to see if the percentage of full-time and/or specialty-certified
      prosthodontic faculty changes.

PMID- 19178620
TI  - Metal-ceramic alloys in dentistry: a review.
AB  - PURPOSE: The purpose of this article is to review basic information about the
      alloys used for fabricating metal-ceramic restorations in dentistry. Their
      compositions, properties, advantages, and disadvantages are presented and
      compared. In addition to reviewing traditional noble-metal and base-metal metal
      ceramic alloys, titanium and gold composite alloys are also discussed. MATERIALS
      AND METHODS: A broad search of the published literature was performed using
      Medline to identify pertinent current articles on metal-ceramic alloys as well as
      articles providing a historical background about the development of these alloys.
      Textbooks, the internet, and manufacturers' literature were also used to
      supplement this information. RESULTS: The review discusses traditional as well as
      more recently-developed alloys and technologies used in dentistry for fabricating
      metal-ceramic restorations. Clear advantages and disadvantages for these alloy
      types are provided and discussed as well as the role that compositional
      variations have on the alloys' performance. This information should enable
      clinicians and technicians to easily identify the important physical properties
      of each type and their primary clinical indications. CONCLUSIONS: A number of
      alloys and metals are available for metal-ceramic use in dentistry. Each has its
      advantages and disadvantages, primarily based on its specific composition.
      Continuing research and development are resulting in the production of new
      technologies and products, giving clinicians even more choices in designing and
      fabricating metal-ceramic restorations.

PMID- 19178622
TI  - The role of the template in prosthetically guided implantology.
AB  - In prosthetically guided implantology, where ideal placement of implants is
      determined by the definitive restoration, the use of a radiographic/surgical
      template plays an essential role. This article describes how to fabricate a
      radiographic/surgical template to be used for radiographic diagnosis of the
      selected implant sites and as a guide during surgery for the insertion of the
      implant with correct angulation.

PMID- 19178623
TI  - Bond strength and degree of infiltration between acrylic resin denture liner
      after immersion in effervescent denture cleanser.
AB  - PURPOSE: The purpose of this study was to investigate the effect of sodium
      perborate on the bond strength and degree of infiltration between acrylic
      resin/resilient denture liners. MATERIALS AND METHODS: Three denture liners
      (Elite Soft, Mucopren Soft, Kooliner) were investigated. Twenty specimens (83 x
      10 x 10 mm(3)) of each material were made by processing the denture liners
      against two polymerized PMMA blocks. Ten specimens for each material were stored
      in artificial saliva at 37 degrees C (control group: TBS1), and the other ten
      specimens were stored in artificial saliva at 37 degrees C combined with sodium
      perborate (experimental group: TBS2). All specimens were placed under tension
      until failure in a Universal Testing Machine at a crosshead speed of 5 mm/min
      after 7 (T7) and 60 (T60) days (n = 5). Failure strength (MPa) was recorded, and
      mode of failure was characterized as cohesive, adhesive, or cohesive/adhesive.
      For the infiltration tests, ten circular specimens (14-mm diameter x 2-mm thick)
      of each material were stored in artificial saliva and 0.5% methylene blue at 37
      degrees C (control group: I1), and ten specimens were stored in artificial saliva
      and 0.5% methylene blue at 37 degrees C combined with daily immersions for 5
      minutes in an effervescent solution of sodium perborate (experimental group: I2).
      The degree of infiltration was obtained through photographs and using Software
      Image Tool after 120 days. RESULTS: For Kooliner, the statistical test did not
      show a significant difference in the bond strength due to the influence of the
      immersion period or to the use of sodium perborate. Elite Soft presented a
      significant increase in the average tension in T7 and in T60 in both TBS1 and
      TBS2. Inversely, the Mucopren suffered a significant decrease in the tension
      value in the same period as the TBS1 group as well as in the TBS2. The
      infiltration percentage was analyzed with the Kruskal-Wallis test (26.18; p <
      0.05), which indicated significant differences between the compared averages for
      the groups. Comparing the averages of materials, the statistical test did not
      show significant differences between the control (I1) and experimental (I2)
      groups after 120 days. CONCLUSIONS: The use of sodium perborate did not promote
      significant alterations in the evaluated properties. Kooliner presented the best
      results.

PMID- 19178624
TI  - Accuracy of impression techniques for implants. Part 2 - comparison of splinting
      techniques.
AB  - PURPOSE: The aim of this study was to compare splinting techniques for impression
      copings of osseointegrated implants with different angulations. MATERIALS AND
      METHODS: Replicas (N = 24) of a metal matrix (control) containing two implants at
      90 degrees and 65 degrees in relation to the horizontal surface were obtained by
      using four impression techniques: Technique 1 (T1), direct technique with square
      copings without union in open trays; Technique 2 (T2), square copings splinted
      with dental floss and autopolymerizing acrylic resin; Technique 3 (T3),square
      copings splinted with dental floss and autopolymerizing acrylic resin, sectioned
      and splinted again with autopolymerizing acrylic resin; Technique 4 (T4), square
      copings splinted with prefabricated acrylic resin bar. The impression material
      was polyether. The replicas were individually scanned to capture the images,
      which were assessed in a graphic computation program. The program allowed the
      angulation between the bases of the replicas and the reading screws to be
      measured. The images of the replicas were compared with the matrix image
      (control), and the differences in angulations from the control image were
      calculated. The analysis of variance and the Tukey test for comparisons (p <
      0.05) were used for statistical analysis. RESULTS: All groups showed significant
      differences in the implant angulations in comparison with the control group (p <
      0.05). Group T1 showed the highest difference (1.019 degrees ) followed by groups
      T2 (0.747 degrees ), T3 (0.516 degrees ), and T4 (0.325 degrees ), which showed
      the lowest angular alteration compared to the control group. There were
      significant differences between inclined and straight implants in all the groups,
      except in group T4. CONCLUSIONS: Based on the results, the splinting of pick-up
      impression copings is indicated for osseointegrated implant impressions. The
      square copings splinted with a prefabricated acrylic resin bar presented the best
      results among the pick-up impression techniques evaluated in this study.

PMID- 19178625
TI  - The new curriculum in radiation oncology-everyone should win!

PMID- 19178626
TI  - Differential diagnosis of T2 hyperintense spinal cord lesions: Part A.
AB  - Hyperintense spinal cord signal on T2-weighted images is seen in a wide-ranging
      variety of spinal cord processes including; simple MR artefacts, congenital
      anomalies and most disease categories. Characterization of the abnormal areas of
      T2 signal as well as their appearance on other MR imaging sequences, when
      combined with clinical context and laboratory investigations, will often allow a
      unique diagnosis, or at least aid in narrowing the differential diagnosis. A wide
      range of instructive cases is discussed here with review of the published reports
      focusing on pertinent MR features to aid in diagnosis.

PMID- 19178627
TI  - Non-contact paediatric knee injuries, including patellar sleeve fractures.
AB  - Different patterns of injury of the knee are seen in children and adults,
      particularly in non-contact injuries. Examples of these are given, including the
      important patella sleeve fracture.

PMID- 19178628
TI  - Benign cardiac tumours: cardiac CT and MRI imaging appearances.
AB  - Primary benign cardiac tumours are rarely found in clinical practice and are
      generally evaluated with echocardiography. However, with the increasing usage of
      helical multislice CT, the initial detection and evaluation of these masses may
      be made by the radiologist during routine daily practice for other indications.
      The echocardiographic, CT and cardiac MRI appearances of various benign cardiac
      tumours and masses are described and illustrated in this review.

PMID- 19178629
TI  - Evaluation of thickness and appearance of anterior talofibular and
      calcaneofibular ligaments in normal versus abnormal ankles with MRI.
AB  - Injuries to the lateral ligaments of the ankle are common in medical practice.
      The most commonly injured ligaments are the anterior talofibular (ATFL) and
      calcaneofibular (CFL) ligaments. When undertaking MRI evaluation of ankle
      injuries it is important to understand the normal dimensions, appearance and
      variations of these ligaments. Twenty-eight consecutive patients referred for MRI
      of the ankle underwent bilateral scanning. The thickness of normal and abnormal
      ATFL and CFL was determined. The mean thickness of the ATFL was 2.19 +/- 0.6 mm
      and the CFL measured 2.13 +/- 0.5 mm. One normal ankle had an extremely thin ATFL
      (0.8 mm) with an otherwise normal appearance, whereas two ankles had an ATFL with
      a high attachment, both of which were deemed to be normal variants. Nineteen per
      cent of normal CFLs were noted to consist of a lateral hypointense band with a
      medial isointense medial band. Two variations of normal ATFL, one normal variant
      CFL and a measurement of the normal thickness of the ATFL and CFL have been
      presented in this paper. These variations have not been described previously by
      other authors. It is envisaged that these findings will assist in the MRI
      assessment of the lateral ankle ligaments.

PMID- 19178630
TI  - 18F-fluorodeoxyglucose positron emission tomography imaging in brain tumours: the
      Western Australia positron emission tomography/cyclotron service experience.
AB  - (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans in the
      first 49 patients referred with either possible brain tumour or brain tumour
      recurrence were reviewed. FDG-PET imaging was reported with reference to
      anatomical imaging. Based on the report the FDG study was classified as either
      positive or negative for the presence of tumour. Thirty-eight cases were included
      in the analysis, 21 having pathological data and 17 with diagnostic clinical
      follow up. Eleven were excluded, as they had inadequate follow-up data. Of the 21
      cases with pathology, 18 were shown to have tumour. In this group there were five
      false-negative scans and two false-positive PET scans. Seventeen cases were
      assessed by clinical follow up, nine were considered to have been tumour. There
      were two false negatives with one false positive. The overall sensitivity,
      specificity and positive and negative predictive values were 74, 73, 87 and 53%
      respectively. This is similar to figures previously quoted in published work.
      Despite relatively limited numbers, the utility of FDG PET imaging in our hands
      is similar to published reports. With a positive predictive value of 87%, a
      positive FDG study indicates a high likelihood that there is brain tumour
      present. A negative study does not exclude the presence of tumour.

PMID- 19178631
TI  - Comparison of vasa vasorum after intravascular stent placement with sirolimis
      drug-eluting and bare metal stents.
AB  - The cytostatic drug, sirolimis has shown prevention in neointimal hyperplasia
      after stent placement. Recent studies have shown persistent inflammation seen
      with drug-eluting stents (DES) may result in late stent thrombosis. The aim of
      this study is to compare effects of bare metal stents (BMS) and sirolimis DES on
      the neointima and vasa vasorum in stented rabbit aortas. Stents were implanted in
      eight New Zealand rabbits for 9 weeks. Group I rabbits received BMS. Group II
      rabbits received sirolimis DES. A balloon-mounted BMS or DES was placed in the
      infrarenal aorta. Following euthanasia, aortas were perfused with barium sulfate
      and sectioned for histology. After 9 weeks the qualitative intrastent luminal
      diameter was fairly uniform in both the DES and the BMS. The thickness of
      neointima was similar in both groups. The number of vasa vasorum in the sirolimis
      DES increased compared with the BMS (P < 0.05). An increased number of vasa
      vasorum produced by the DES when compared with the BMS shows a difference in
      response to local vessel injury in rabbits. This result suggests that vasa
      vasorum may play a role in the persistent inflammation generated by sirolimis
      coated stents.

PMID- 19178632
TI  - Percutaneous antegrade ureteric stent removal using a rigid alligator forceps.
AB  - To evaluate the safety and efficacy of percutaneous antegrade ureteric stent
      removal using a rigid alligator forceps. Twenty patients were included in our
      study. Indications for ureteric stent insertion included stone disease (n = 7),
      malignancy (n = 8) and transplant anastomotic strictures (n = 5). Stent retrieval
      was carried out for proximal stent placement/migration in seven patients and
      encrustation in the remaining 13. Twenty-two stents were successfully retrieved
      in 20 patients. There was one technical failure (5%). There were no major
      complications. We had four minor complications, which included nephrostomy site
      pain (n = 2), periprocedural sepsis (n = 1) and a small urinoma (n = 1). All
      patients settled with conservative management. Percutaneous radiologically guided
      antegrade ureteric stent removal with an alligator forceps is safe and effective,
      particularly when initial surgical removal has failed.

PMID- 19178633
TI  - Liver metastasis of a mucinous colonic carcinoma mimicking a haemangioma in T2
      weighted sequences.
AB  - We report the case of a patient with a single liver metastasis of a mucinous
      colonic carcinoma that mimics a haemangioma in T2-weighted sequences. Although a
      very high T2 signal in non-cystic lesions is highly specific for the diagnostic
      of haemangioma, the use of gadolinium-enhancement MRI is recommended. In patients
      with a history of neoplasia, the diagnosis of benign liver nodules should be made
      with caution.

PMID- 19178635
TI  - Brachytherapy for cancer of the cervix: an Australian and New Zealand survey of
      current treatment techniques.
AB  - Establishing guidelines for the practice of brachytherapy throughout Australia
      and New Zealand is one of the goals of the Australasian Brachytherapy Group. To
      better appreciate Australasian resources and conditions, the group conducted a
      survey in early 2005. The aims were to survey current practices, to emphasize
      variations in practice and to determine the availability of advanced imaging and
      treatment methods to assess resources. A survey was sent to all Australian and
      New Zealand radiotherapy departments. The survey requested details of treatment
      with respect to external beam radiotherapy, brachytherapy, optimization methods,
      reporting methods, scheduling brachytherapy and access to imaging and methods of
      work-up. Thirty-four departments were contacted with 27 (79%) responses returned.
      Twenty-one departments use brachytherapy. Doses and fractionation schedules
      varied and use of sectional imaging was minimal. Individualized dosimetry is
      practised in a limited fashion by 60% of the surveyed departments. There is high
      compliance with International Commission on Radiation Units 38 dose reporting
      recommendations. All brachytherapy units identified have access to CT and 85% to
      MRI within the hospital settings. Brachytherapy for cancer of the cervix is,
      currently, largely based on the Manchester system. The survey did emphasize
      considerable variation in dose and fractionation schemes between departments. The
      Australasian Brachytherapy Group subgroup intends to proceed with the process of
      formulating recommendations for cervix brachytherapy. It is intended that these
      will cover the use of image-based planning and treatment, target definition(s),
      verification of brachytherapy treatments and a uniform dose-reporting mechanism.

PMID- 19178634
TI  - Salvage definitive chemo-radiotherapy for locally recurrent oesophageal carcinoma
      after primary surgery: retrospective review.
AB  - To determine the overall survival and gastrointestinal toxicity for patients
      treated with salvage definitive chemo-radiotherapy after primary surgery for
      locoregional relapse of oesophageal carcinoma. A retrospective review of 525
      patients who had a resection for oesophageal or oesophagogastric carcinoma at
      Princess Alexandra Hospital identified 14 patients treated with salvage
      definitive radiotherapy or chemo-radiotherapy, following localized recurrence of
      their disease. We analysed the patient and treatment characteristics to determine
      the median overall survival as the primary end point. Gastrointestinal toxicity
      was examined to determine if increased toxicity occurred when the stomach was
      irradiated within the intrathoracic radiotherapy field. The median overall
      survival for patients treated with curative intent using salvage definitive chemo
      radiotherapy was 16 months and the 2-year overall survival is 21%. One patient is
      in clinical remission more than 5 years after therapy. Age <60 years old and
      nodal recurrence were favourable prognostic factors. Treatment compliance was 93%
      with only one patient unable to complete the intended schedule. Fourteen per cent
      of patients experienced grade 3 or 4 gastrointestinal toxicity. Salvage
      definitive chemo-radiotherapy should be considered for good performance status
      patients with oesophageal carcinoma who have a locoregional relapse after primary
      surgery. The schedule is tolerable with low toxicity and an acceptable median
      survival.

PMID- 19178636
TI  - Accrediting radiation technique in a multicentre trial of chemoradiation for
      pancreatic cancer.
AB  - Before a multicentre trial of 3-D conformal radiotherapy to treat cancer of the
      pancreas, participating clinicians were asked to complete an accreditation
      exercise. This involved planning two test cases according to the study protocol,
      then returning hard copies of the plans and dosimetric data for review. Any
      radiation technique that achieved the specified constraints was allowed. Eighteen
      treatment plans were assessed. Seven plans were prescribed incorrect doses and
      two of the planning target volumes did not comply with protocol guidelines. All
      plans met predefined normal tissue dose constraints. The identified errors were
      attributable to unforeseen ambiguities in protocol documentation. They were
      addressed by feedback and corresponding amendments to protocol documentation.
      Summary radiobiological measures including total weighted normal tissue
      equivalent uniform dose varied significantly between centres. This accreditation
      exercise successfully identified significant potential sources of protocol
      violations, which were then easily corrected. We believe that this process should
      be applied to all clinical trials involving radiotherapy. Due to the limitations
      of data analysis with hard-copy information only, it is recommended that complete
      planning datasets from treatment-planning systems be collected through a digital
      submission process.

PMID- 19178637
TI  - Survey of the learning activities of Australasian radiation oncology specialist
      trainees.
AB  - Trainee radiation oncologists must master a substantial body of skills and
      knowledge to become competent specialists. The resources available to support
      this are limited. We surveyed the 90 registrars enrolled in the Royal Australian
      and New Zealand College of Surgeons (RANZCR) radiation oncology training
      programme to obtain a range of information about their learning activities (with
      a significant focus on part 1 teaching). Responses were received from 59
      registrars (66% of those eligible). Trainees reported spending a median 2.5 h per
      week (range 0-10 h) in formal teaching activities. With regard to part 1 exam
      preparation, 83% reported having had physics teaching--the median quality was
      5/7; 88% had radiobiology teaching--the median quality was 4/7; 52% had anatomy
      teaching--the median quality was 3/7. Registrars training within the RANZCR
      radiation oncologists training programme perceive their own clinical learning
      environment as generally good; however' 50% of respondents felt that more
      teaching was needed for part 1 subjects. This compared with only 19% of
      respondents who felt that more teaching was required for part 2 exam preparation.
      Innovative solutions, such as centralized web-based teaching, may help to address
      weaknesses in part 1 teaching. With increasing demands on radiation oncologists
      and trainees it will be important to monitor learning environments.

PMID- 19178638
TI  - A simple and inexpensive method to routinely produce customized neck supports for
      patient immobilization during radiotherapy.
AB  - Accurate and reproducible patient positioning is fundamental to the success of
      fractionated radiotherapy. Poor patient positioning could result in geographic
      misses. We have recently reported on an improved method of customized face mask
      production using laser surface scanning. In this report, we sought to identify
      and develop a method to routinely make customized neck supports for patients
      prescribed radiotherapy to the brain or head and neck regions. We identified a
      potentially suitable product--sealed packs containing two liquids that produce
      expanding polyurethane foam when mixed--and developed a method for their use. The
      neck supports are inexpensive and simple to produce (taking less than 5 min of
      radiation therapist labour). We assessed the customized neck supports in several
      ways. The effect on setup accuracy was assessed by comparing two consecutive
      cohorts of patients. Statistically significant differences favouring the
      customized neck supports included a reduced total displacement error (mean 3.4
      vs. 2.1 mm) and a reduced left-right setup error (mean 1.8 vs. 1.1 mm). This is
      consistent with the greater support provided by the customized neck supports.
      This method could easily be undertaken by other departments.

PMID- 19178639
TI  - Clinically diagnosed glomus vagale tumour treated with external beam
      radiotherapy: a review of the published reports.
AB  - The aim of the study was to present a case of clinically diagnosed glomus vagale
      in a 42-year-old Aboriginal woman treated with external beam radiotherapy and to
      carry out a review of the published work. The details of presentation, diagnosis,
      treatment and follow up of the patient are discussed. A review of the published
      work was carry out using MEDLINE database with respect to aetiology, clinical
      presentation, diagnosis, treatment and expected outcomes. Glomus vagale tumours
      are a subtype of paragangliomas of the head and neck derived from extra-adrenal
      paraganglia of the autonomic nervous system. They are typically slow-growing,
      benign masses that are often asymptomatic and rarely show signs of
      hypersecretion. Treatment options include embolization, surgical excision,
      radiotherapy or surveillance. Radiotherapy is often used for extensive lesions
      where surgery is considered prohibitively morbid. Following treatment relapse
      rates are low with the most patients achieving long-term control. Our patient
      presented with an extensive lesion compressing the wall of the carotid artery and
      invading the jugular fossa to involve the clivus. Surgery was offered; however,
      the patient opted for external beam radiotherapy. A dose of 45 Gy in 25 fractions
      was delivered with 6-MV photons employing a CT-planned, wedge pair technique.
      Glomus vagale tumours are rare and should be managed in a multidisciplinary head
      and neck clinic with both surgical and radiation oncology opinions offered. The
      toxicities and outcomes of both methods should be discussed.

PMID- 19178640
TI  - Stereotactic radiotherapy for the treatment of neurosarcoidosis involving the
      pituitary gland and hypothalamus.
AB  - We report the case of a 38-year-old, female patient with neurosarcoidosis
      involving the pituitary gland and hypothalamus, who was treated with stereotactic
      radiotherapy (24 Gy in 12 fractions) with an excellent result. The purpose of
      this case report was to illustrate and discuss the diagnostic and therapeutic
      challenges faced in the management of neurosarcoidosis, as well as document our
      experience with the use of stereotactic radiotherapy in the treatment of
      neurosarcoidosis.

PMID- 19178641
TI  - Multidisciplinary meetings: patient expectations and legal liability.

PMID- 19178644
TI  - The upregulation of cystatin C in human gingival fibroblasts stimulated with
      cyclosporine A.
AB  - BACKGROUND AND OBJECTIVE: Cystatin C is a 13 kDa non-glycosylated, basic protein
      belonging to the cystatin family. It is consistently and dramatically upregulated
      in a variety of fibrotic diseases. However, little is known about the correlation
      between cystatin C and cyclosporine A-induced gingival overgrowth. The aim of
      this study was to compare cystatin C expression in normal, healthy gingival
      tissues and cyclosporine A-induced gingival overgrowth specimens and further
      explore the potential mechanism that may result in cystatin C expression.
      MATERIAL AND METHODS: Fifteen cyclosporine A-induced gingival overgrowth
      specimens and five normal gingival tissues were examined by immunohistochemistry.
      Three human gingival fibroblast (HGF) strains were established from crown
      lengthening surgery. The reverse transcriptase-polymerase chain reaction was used
      to investigate the effects on HGFs exposed to cyclosporine A. In addition,
      predominant periodontal pathogens (Aggregatibacter actinomycetemcomitans and
      Porphyromonas gingivalis) and proinflammatory cytokines (interleukin-1alpha and
      tumor necrosis factor-alpha) were added to seek the possible regulatory
      mechanisms of cystatin C expression. RESULTS: The cystatin C staining in gingival
      tissue was stronger in the cyclosporine A-induced gingival overgrowth group than
      in the normal gingival group (p < 0.05). Intensive staining for cystatin C
      expression was observed mainly in the cytoplasm of fibroblasts, epithelial cells
      and inflammatory cells. Moreover, cystatin C expression was significantly higher
      in cyclosporine A-induced gingival overgrowth specimens with higher levels of
      inflammatory infiltrates (p < 0.05). A concentration of 200 ng/mL cyclosporine A
      was found to increase cystatin C expression in HGFs in a time-dependent manner (p
      < 0.05). The addition of periodontal pathogens and proinflammatory cytokines
      significantly increased the expression of cystatin C compared with cyclosporine A
      alone (p < 0.05). CONCLUSION: The increased ability of protein accumulation by
      cystatin C is one of several factors mediating cyclosporine A-induced gingival
      overgrowth. In addition, cyclosporine A may predispose to gingival overgrowth in
      inflammatory environments.

PMID- 19178645
TI  - Effect of the dental adhesive, 4-META/MMA-TBB resin, on adhesion and
      keratinization of regenerating oral epithelium.
AB  - BACKGROUND AND OBJECTIVE: The 4-META/MMA-TBB [4-(2-methacryloxyethyl)trimellitic
      anhydride/methyl methacrylate-tributylborane] resin is widely used as a dental
      adhesive. It has also been applied in the dressing of gingival wound surfaces
      following periodontal surgery. However, its effect on the regeneration and/or
      cell attachment of the oral epithelium remains to be clarified. To evaluate the
      effect of the resin applied as a wound dressing, we investigated expression of
      laminin 5, integrin beta(4) and cytokeratin 14 in regenerating oral epithelium
      treated with this resin following gingivectomy from the viewpoint of cell
      attachment and differentiation. MATERIAL AND METHODS: The resin was applied to
      the entire wound surface in rats after gingival surgery, and regenerating
      epithelium was examined immediately and at 1, 3, 5, 7 and 14 days later. The
      resin was removed 2 weeks after application in some animals and tissue further
      examined at 1, 3, 5 and 7 days later. RESULTS: Regenerating epithelium under the
      resin was not keratinized, but became keratinized immediately after removal of
      the resin. Laminin 5 and integrin beta(4) were immunolocalized in the basal
      lamina, the internal basal lamina, in marginal cells of the regenerating
      epithelium and at the resin-regenerating epithelium interface. Cytokeratin 14
      localized in the regenerating epithelium underneath the resin, as well as in
      healthy and regenerated junctional epithelial cells. CONCLUSION: These results
      suggest that this resin covers the wound surface and that the regenerating
      epithelium biologically adheres to the resin during the initial process of its
      regeneration.

PMID- 19178646
TI  - Hyperosmolar coma due to exclusive glucose accumulation: recognition and
      computations.
AB  - AIM: To avoid electrolyte derangements during correction of hyperosmolar coma
      (HC), PNa(PREDICTED) at the end of correction is presently estimated from plasma
      glucose (P(G), mM/L). When the rise in plasma osmolality (Posm) is entirely due
      to glucose addition (G(A), mM) to the extracellular volume (ECV), this PNa
      prediction can be improved by correctly estimating G(A) and any associated water
      loss (DeltaV), while excluding any concomitant Na loss (DeltaNa). METHODS:
      Indicating with (0) the normal conditions, with (1) the HC,DeltaPosm=P(G1)xECV1
      establishes an exclusive G(A) accumulation. We derived the equations for
      computing G(A), DeltaV and PNa(PREDICTED). Computer simulations of HC were
      performed by adding the known G(A) while subtracting the known DeltaV and DeltaNa
      in different combinations, obtaining exact values of PNa(1) and P(G1). Applying
      our formulas, we recognized and discarded all cases with concomitant DeltaNa, and
      we computed G(A), DeltaV and PNa (PREDICTED) from PNa(1) and P(G1), as if they
      had been measured in patients. We extended these same calculation algorithms to
      68 patients with HC. RESULTS: In computer simulations, true and calculated G(A),
      DeltaV and PNa(PREDICTED) were identical, such that regression and correlation
      coefficients were 1 (P < 0.0001). Out of the 68 patients recruited, 13 fulfilled
      the boundary conditions of an exclusive G(A) addition. The true values, obtained
      by balance studies performed on these patients, were not different from and
      significantly correlated with the calculated data (R(2) = 0.99, P < 0.001).
      CONCLUSION: Our new model system for HC and the new formulas improve to near
      exactness the accuracy in estimating PNa(PREDICTED), helping the physician to
      avoid unwanted electrolyte derangements during treatment.

PMID- 19178647
TI  - Longitudinal and cross-sectional influences on youth fruit and vegetable
      consumption.
AB  - Both cross-sectional and longitudinal research depict a decline in the fruit and
      vegetable consumption (FVC) of children and youths with age, but identifying
      developmental changes and their influences with regard to FVC cannot be fully
      explained with application of only one of these research designs. Reviewed here
      are results from longitudinal and cross-sectional research, and a proposal is
      presented for a lifespan development methodology that uses a sequential design
      strategy to illuminate the multilevel processes that determine FVC. Conclusions
      from the review were similar for both cross-sectional and longitudinal research,
      with fruit and vegetable (FV) preferences and FV accessibility/availability being
      the most consistent influences on FVC. Furthermore, this review illuminates
      several methodological issues, offering suggestions to strengthen comparisons
      between studies. Research designs that incorporate longitudinal, cross-sectional,
      and time-lag data are warranted.

PMID- 19178648
TI  - Cross-talk of human gut with bifidobacteria.
AB  - The gut constitutes a prominent part of the immune system. Its commensal
      microflora plays an important role in defense and in tolerance to diet allergens.
      Disturbances in immune regulations may lead to food allergy. Among commensal
      bacteria, bifidobacteria are able to induce mechanisms of immune tolerance.
      Comprehension of their mutual cross-talk with the host is necessary for
      understanding their role in the diet and in food supplements.

PMID- 19178649
TI  - The freshman weight gain phenomenon revisited.
AB  - Earlier studies associated the first year of college with a dramatic increase in
      body weight, termed the "freshman 15". However, recent studies showed that weight
      gain might be smaller. The purpose of this review was to evaluate the extent of
      observed weight/body composition changes, including factors associated with them,
      among students entering university. Searches were conducted for studies examining
      weight/body composition changes during freshman semesters. Most studies were not
      comprehensive in assessing numerous potential causative factors for weight gain.
      Methods for assessing diet, physical activity, and behavioral factors varied
      among studies. Weight changes were often not quantified by measures of body
      composition (lean/fat) to ascertain that changes were limited just to gains in
      fat mass. Overall, weight changes ranged from 0.7-3.1 kg, but among individuals
      who gained weight, the range was narrower, 3.1-3.4 kg. There may be specific
      groups of students with a greater predisposition for weight gain and future
      research should focus on identifying those groups.

PMID- 19178650
TI  - Animal experimentation--a personal view.
AB  - Disagreement about the use of animals in biomedical research has resulted in
      absurd positions by both sides. Increasingly, some zealots against animal
      experimentation have resorted to violence or other illegal acts to support their
      points of view. The value of animal research in providing better health for man
      and animals is incontrovertible. This is illustrated by references to animal
      research in the field of nutrition.

PMID- 19178651
TI  - Iron deficiency and obesity: the contribution of inflammation and diminished iron
      absorption.
AB  - Poor iron status affects billions of people worldwide. The prevalence of obesity
      continues to rise in both developed and developing nations. An association
      between iron status and obesity has been described in children and adults. The
      mechanism explaining this relationship remains unknown; however, findings from
      recent reports suggest that body mass index and inflammation predict iron
      absorption and affect the response to iron fortification. The relationship
      between inflammation and iron absorption may be mediated by hepcidin, although
      further studies will be required to confirm this potential physiological
      explanation for the increased prevalence of iron deficiency in the obese.

PMID- 19178652
TI  - Is calcium supplementation a risk factor for cardiovascular diseases in older
      women?
AB  - Low intake of dietary calcium is related to bone loss and fragility fracture in
      older adults, especially postmenopausal women. Contradictory findings have been
      reported from studies that investigated the association between calcium
      supplementation and hypertension and the risk of stroke and cardiovascular
      disease. Misinterpretation of findings from studies that are not primarily
      designed to address these issues might overshadow the benefits of dietary
      calcium. Until well-designed studies address the current uncertainties, the
      possible detrimental effect (e.g., hypercalcemia and its complications) of higher
      than-recommended calcium intake should be balanced against the likely benefits of
      calcium on bone, particularly in elderly women.

PMID- 19178653
TI  - Recent developments in intestinal calcium absorption.
AB  - Calcium absorption proceeds by transcellular and paracellular flux, with the
      latter accounting for most absorbed calcium when calcium intake is adequate.
      Vitamin D helps regulate transcellular calcium transport by increasing calcium
      uptake via a luminal calcium channel and by inducing the cytosolic calcium
      transporting protein, calbindinD(9k). Recent studies utilizing knockout mice have
      challenged the functional importance of the channel and calbindin. To integrate
      the new findings with many previous studies, the function of the two molecules
      must be evaluated in the calcium transport and economy of mice. When calcium
      intake is high, transcellular calcium transport contributes little to total
      calcium absorption. Therefore, increasing calcium intake seems the most effective
      nutritional approach to ensure adequate absorption and prevent bone loss.

PMID- 19178654
TI  - Physical Activity Guidelines Advisory Committee report, 2008. To the Secretary of
      Health and Human Services. Part A: executive summary.

PMID- 19178655
TI  - A weight-based formula for tracheal tube size in children.
AB  - OBJECTIVE: Age (in years) of the child has conventionally been used in formulae
      to estimate the tracheal tube (TT) size. The objective of this retrospective
      study was to test a weight-based formula (WBF) for uncuffed oral TT in children
      and compare it with the conventional age-based formula (ABF). METHODS: The
      patient's age, weight, and size of TT internal diameter (ID) were recorded. For
      comparative analysis, the actual TT size used was compared with predicted TT
      size, calculated using both the standard ABF [ID = age (years)/4 + 4 mm] and the
      WBF [ID = weight (kg)/10 + 3.5 mm]. RESULTS: The Pearson's correlation
      coefficient for age and actual TT size used was 0.77 (95% CI: 0.74-0.80) and
      between weight and actual TT used was 0.70 (95% CI: 0.66-0.74). The ABF correctly
      predicted 51.3% of TT sizes while the WBF correctly predicted 44.8% of TT sizes
      (P = 0.01). The measures of agreement between the actual and predicted TT size
      were 0.35 and 0.27 for the ABF and WBF respectively. The difference between the
      percentages of paired predictions for the ABF and WBF was statistically
      significant (P < 0.001) suggesting that, when correctly predicting the actual
      tube size used, the WBF functions for a different subset of the patient cohort
      than the ABF. CONCLUSIONS: This study suggests that in this patient cohort, the
      WBF is statistically inferior to the conventional ABF. However, our findings also
      suggest that the WBF may correctly predict TT sizes in a subset of patients in
      whom the ABF is inaccurate.

PMID- 19178656
TI  - Nuclear risk management on stage: a decision analysis perspective on the UK's
      Committee on Radioactive Waste Management.
AB  - In 2003, the UK government set up a broad-based Committee on radioactive waste
      management (CoRWM) to look at the UK's policy on radioactive waste management
      with a view to jumpstarting a stalled policy process. The committee's brief was
      to come up with a set of recommendations that would protect the public and the
      environment, and be capable of inspiring public confidence. After consulting
      widely with the public and stakeholders, and drawing on advice from scientists
      and other experts, CoRWM arrived at a remarkably well-received set of
      recommendations. On the basis of our experiences of working on CoRWM's multi
      criteria decision analysis of different management options, study of CoRWM
      documentation, and interviews with committee members, we describe the explicit
      and implicit principles that guided CoRWM. We also give an account of the process
      by which CoRWM arrived at its conclusions, covering four phases: framing,
      shortlisting, option assessment, and integration; and four cross-cutting
      activities: public and stakeholder engagement (PSE), science and engineering
      input, ethics and social science input, and learning from overseas practice. We
      finish by outlining some of the key developments in the UK's radioactive waste
      management process, which followed on from the publication of CoRWM's report, and
      present our reflections for the benefit of the risk and decision analysts of
      future committees that, like CoRWM, are charged with recommending to government
      on the management of technically complex and risky technologies, drawing on
      extensive public and stakeholder consultation.

PMID- 19178657
TI  - Changes in Aleut concerns following the stakeholder-driven Amchitka independent
      science assessment.
AB  - There is widespread agreement that stakeholders should be included in the problem
      formulation phase of addressing environment problems and, more recently, there
      have been attempts to include stakeholders in other phases of environmental
      research. However, there are few studies that evaluate the effects of including
      stakeholders in all phases of research aimed at solving environmental problems.
      Three underground nuclear blasts were detonated on Amchitka Island from 1965 to
      1971. Considerable controversy developed when the Department of Energy (DOE)
      decided to "close" Amchitka. Concerns were voiced by subsistence Aleuts living in
      the region, resource trustees, and the State of Alaska, among others. This
      article evaluates perceptions of residents of three Aleutian village before
      (2003) and after (2005) the Consortium for Risk Evaluation with Stakeholder
      Participation's (CRESP) Amchitka Independent Science Assessment (AISA). The CRESP
      AISA provided technical information on radionuclide levels in biota to inform
      questions of seafood safety and food chain health. CRESP used the questions asked
      at public meetings in the Aleut communities of Atka, Nikolski, and Unalaska to
      evaluate attitudes and perceptions before and after the AISA. Major concerns
      before the AISA were credibility/trust of CRESP and the DOE, and information
      about biological methodology of the study. Following the AISA, people were most
      concerned about health effects and risk reduction, and trust issues with CRESP
      declined while those for the DOE remained stable. People's relative concerns
      about radionuclides declined, while their concerns about mercury (not addressed
      in the AISA) increased, and interest in ecological issues (population changes of
      local species) and the future (continued biomonitoring) increased from 2003 to
      2005. These results suggest that questions posed at public meetings can be used
      to evaluate changes in attitudes and perceptions following environmental
      research, and the results are consistent with the hypothesis that the AISA
      answered questions about radionuclides, and lowered overall concern about
      radionuclides, but left unanswered concerns about the health effects of mercury.

PMID- 19178658
TI  - Cooking practices in the kitchen-observed versus predicted behavior.
AB  - Cross-contamination and undercooking are major factors responsible for
      campylobacteriosis and as such should be incorporated in microbiological risk
      assessment. A previous paper by van Asselt et al.((1)) quantified cross
      contamination routes from chicken breast fillet via hand, cutting board, and
      knife ending up in a prepared chicken-curry salad in the domestic kitchen. The
      aim of the current article was to validate the obtained transfer rates with
      consumer data obtained by video observations and microbial analyses of a home
      prepared chicken-curry salad. Results showed a wide range of microbial
      contamination levels in the final salad, caused by various cross-contamination
      practices and heating times varying from 2'44'' to 41'30''. Model predictions
      indicated that cooking times should be at least 8 minutes and cutting boards need
      to be changed after cutting raw chicken in order to obtain safe bacterial levels
      in the final salad. The model predicted around 75% of the variance in cross
      contamination behavior. Accuracy of the model can further be improved by
      including other cross-contamination routes besides hands, cutting boards, and
      knives. The model proved to be fail-safe, which implies it can be used as a worst
      case estimate to assess the importance of cross-contamination in the home.

PMID- 19178659
TI  - Cisplatin: a review of toxicities and therapeutic applications.
AB  - Cisplatin is a platinum chemotherapeutic used in a variety of malignancies. The
      antineoplastic activity occurs from DNA cross-links and adducts, in addition to
      the generation of superoxide radicals. Nephrotoxicity is the most well-known and
      potentially most clinically significant toxicity. Unfortunately, the mechanism
      for cisplatin nephrotoxicity has not been completely elucidated; however, many
      theories have been developed. Other toxicities include gastrointestinal,
      myelosuppression, ototoxicity and neurotoxicity. Saline diuresis is currently the
      most accepted way to prevent cisplatin nephrotoxicity. Research has focused on
      pharmaceuticals and enzyme/molecular alterations as alternatives to long-term
      diuresis. No agents have currently been identified that can protect from all
      toxicities. Cisplatin has shown activity against osteosarcoma, transitional cell
      carcinoma, squamous cell carcinoma (SCC), melanoma, mesothelioma, carcinomatosis
      and germinal cell tumours in the dog. In the cat, cisplatin cannot be utilized
      because of fulminant pulmonary oedema that occurs at standard doses.
      Intralesional cisplatin has been utilized in horses for the treatment of SCC and
      sarcoids.

PMID- 19178660
TI  - Cranial mediastinal carcinomas in nine dogs.
AB  - Nine dogs were diagnosed with cranial mediastinal carcinomas. Based on
      histological and immunohistochemical analysis, four dogs were diagnosed with
      ectopic follicular cell thyroid carcinomas, one dog with ectopic medullary cell
      thyroid carcinoma, two dogs with neuroendocrine carcinomas and two dogs with
      anaplastic carcinomas. Clinical signs and physical examination findings were
      associated with a space-occupying mass, although one dog was diagnosed with
      functional hyperthyroidism. Surgical resection was attempted in eight dogs. The
      cranial mediastinal mass was invasive either into the heart or into the cranial
      vena cava in three dogs. Resection was complete in six dogs and unresectable in
      two dogs. All dogs survived surgery, but four dogs developed pulmonary
      thromboembolism and two dogs died of respiratory complications postoperatively.
      Adjunctive therapies included pre-operative radiation therapy (n=1) and
      postoperative chemotherapy (n=3). Three dogs had metastasis at the time of
      diagnosis, but none developed metastasis following surgery. The overall median
      survival time was 243 days. Local invasion, pleural effusion and metastasis did
      not have a negative impact on survival time in this small case series.

PMID- 19178661
TI  - Oesophageal leiomyosarcoma in dogs: surgical management and clinical outcome of
      four cases.
AB  - Oesophageal leiomyosarcoma has yet to be reported in dogs. This retrospective
      case series describes the case management and clinical outcome of four dogs with
      oesophageal leiomyosarcoma treated by marginal excision alone. Histological
      features used to determine tumour grade included capsular invasion, percent
      necrosis, pleomorphism and mitotic rate. All tumours were designated grade 1
      leiomyosarcoma. Excision of all grossly evident tumour tissue was achieved in two
      of the four cases; however, histopathologic evaluation showed tumour cells at the
      surgical margins in one of these two cases. Two dogs had grossly incomplete
      excision. Two dogs died from unrelated conditions, one 3 years and 5.5 months
      after surgery, the other at 65 days. One dog had persistent mega-oesophagus and
      was lost to follow-up 388 days after surgery and one dog is still alive (last
      follow-up 405 days after surgery). Despite large tumour size and incomplete
      excision, surgical removal of low-grade leiomyosarcomas can result in long-term
      resolution of clinical signs.

PMID- 19178663
TI  - Use of imiquimod 5% cream (Aldara) in cats with multicentric squamous cell
      carcinoma in situ: 12 cases (2002-2005).
AB  - Multicentric squamous cell carcinoma in situ (MSCCIS) is a variant of squamous
      cell carcinoma in cats, commonly referred to as Bowen's-like disease. Imiquimod
      5% cream (Aldara) is a novel immune response modifier (IRM) that has been
      reported as a successful treatment for Bowen's disease in humans. The purpose of
      this study was to describe clinical findings, treatment protocols and survival in
      cats with MSCCIS treated with imiquimod 5% cream and to examine the effects of
      imiquimod 5% cream in cats with MSCCIS. The expression of papillomavirus group
      specific antigen in the study population was also determined. From review of
      medical records, 12 cats were identified with a histologic diagnosis of MSCCIS
      and treatment with imiquimod 5% cream. Initial lesions responded to imiquimod 5%
      cream in all cats. Most cats (75%) developed new lesions. New lesions also
      responded to imiquimod 5% cream in all cats treated. Five cats (41%) had side
      effects suspected to be associated with the use of imiquimod 5% cream, including
      local erythema (25%), increased liver enzymes and neutropenia (8%), and partial
      anorexia and vomiting (8%). Kaplan-Meier median treatment duration and median
      survival time probabilities for cats in this study were 1189 days, respectively.
      A time to failure model was generated as many cats were censored from analysis
      well before the aforementioned projected median. This model resulted in a shorter
      median survival time of 243 days. No patient-related, tumour-related or treatment
      related prognostic variables were identified. No expression for papilloma group
      specific antigen was found. Imiquimod 5% cream appears to be well tolerated in
      the majority of cats, and further studies are warranted to further examine its
      usefulness in cats with this disease.

PMID- 19178662
TI  - NOD/SCID mouse model of canine T-cell lymphoma with humoral hypercalcaemia of
      malignancy: cytokine gene expression profiling and in vivo bioluminescent
      imaging.
AB  - Lymphoma is a malignant neoplasm arising from B or T lymphocytes. In dogs, one
      third of lymphomas are highly aggressive multicentric T-cell lymphomas that are
      often associated with humoral hypercalcaemia of malignancy (HHM). There are no
      cell lines or animal models to investigate the pathogenesis of T-cell lymphoma
      and HHM in dogs. We developed the first xenograft model by injecting lymphoma
      cells from an Irish Wolfhound intraperitoneally into NOD/SCID mice. The mice
      developed multicentric lymphoma along with HHM and increased parathyroid hormone
      related protein (PTHrP) as occurs in dogs with T-cell lymphoma. Using cytokine
      complementary DNA arrays, we identified genes that have potential implications in
      the pathogenesis of T-cell lymphoma. Quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) of T-cell lymphoma samples from hypercalcaemic
      canine patients showed that PTHrP likely plays a central role in the pathogenesis
      of HHM and that hypercalcaemia is the result of a combinatorial effect of
      different hypercalcaemic factors. Finally, we monitored in vivo tumour
      progression and metastases in the mouse model by transducing the lymphoma cells
      with a lentiviral vector that encodes a luciferase-yellow fluorescent protein
      reporter and showed that in vivo trafficking patterns in this model were similar
      to those seen in dogs. This unique mouse model will be useful for translational
      research in lymphoma and for investigating the pathogenesis of T-cell lymphoma
      and HHM in the dog.

PMID- 19178666
TI  - Retrospective--systematic study and quantitative analysis of cellular
      proliferation and apoptosis in normal, hyperplastic and neoplastic perianal
      glands in dogs.
AB  - Neoplasms in the perianal region are frequently diagnosed in dogs. The aetiology
      is unknown, and most of them are benign. In this study, 240 neoplasms of the
      perianal glands of dogs were retrieved from the Department of Pathology archives
      of the Faculty of Veterinary Medicine and Zootechny of University of Sao Paulo
      (FMVZ/USP), from 1984 to 2004. All 240 cases were re-examined by two
      pathologists. Nine cases (4%) were diagnosed as hyperplasia, 49 (20%) as group I
      adenoma, 81 (34%) were classified as moderately differentiated adenomas of the
      group II, 46 (19%) were poorly differentiated adenomas of group II, 48 (20%) were
      carcinoma of the group III according to the classification proposed by Berrocal,
      and 7 (13%) were other kind of tumours. Males over 8 years of age were
      predominantly affected. Cell proliferation was quantified by counting
      proliferating cell nuclear antigen (PCNA) positive nuclei, and apoptosis was
      quantified by counting fluorescent eosin-stained apoptotic corpuscles (AC) in
      normal tissue, hyperplasia and in different histologic types of neoplasia of
      these glands. A parallel pattern of increase in both parameters (cell
      proliferation and apoptosis) was obtained. The net growth index (NGI), represents
      how much a cell population is proliferating or dying and was achieved by dividing
      the mean PCNA count in 1000 cells by the mean AC stain count in 1000 cells. NGI
      was different between hyperplasia and neoplasia; group I adenomas have a much
      higher potential of growth, and NGI decreases from benign towards malignant
      lesions. These results show up the importance of studying cell proliferation and
      apoptosis to understand the carcinogenesis of dog perianal gland.

PMID- 19178668
TI  - Adjuvant gemcitabine after surgical removal of aggressive malignant mammary
      tumours in dogs.
AB  - Canine mammary tumours are generally treated with surgery alone, despite the fact
      that 50% of them are malignant and many will eventually lead to recurrence or
      metastases. A prospective clinical trial in which dogs with aggressive mammary
      carcinoma of clinical stages IV and V were treated with surgical excision (n = 9)
      or with surgery and adjuvant weekly gemcitabine (n = 10) for at least four cycles
      was conducted. Gemcitabine was given as an intravenous infusion at the dose of
      800 mg m(-2). Aim of the study was to explore potential beneficial effects of
      gemcitabine on time to local recurrence (TTR), time to distant metastases (TTM)
      and overall survival (OS) in canine patients with operated mammary tumours
      bearing high risk for locoregional failure and distant metastases. Also, factors
      associated with OS, including neutering status, body weight, age, clinical stage
      at presentation, tumour size, histological grade and, in dogs receiving
      chemotherapy, the number of gemcitabine treatments, were investigated. Finally,
      acute toxicities related to chemotherapy and quality of life were assessed in
      dogs receiving gemcitabine. Dogs treated with surgery alone or surgery followed
      by gemcitabine had no difference in TTR, TTM or OS (P > 0.05). In the group of
      dogs receiving adjuvant chemotherapy, the number of gemcitabine treatments was
      positively correlated with OS (P = 0.017). Gemcitabine treatment was well
      tolerated, with no dogs experiencing clinically relevant haematological or
      gastrointestinal toxicity. Despite being safe at the present dose, gemcitabine
      chemotherapy as an adjunct treatment to surgical excision may not be recommended
      in dogs with aggressive mammary carcinoma.

PMID- 19178667
TI  - Cytosine arabinoside in addition to VCAA-based protocols for the treatment of
      canine lymphoma with bone marrow involvement: does it make the difference?
AB  - Cytosine arabinoside (ara-C) is a component of many protocols for the treatment
      of acute leukaemia and non-Hodgkin lymphomas in humans. The aim of the study was
      to prospectively evaluate the efficacy of ara-C in a myeloablative regimen in a
      cohort of canine lymphomas with bone marrow involvement. Seventeen dogs were
      enrolled. Eight were treated with a VCAA-based protocol (Group 1) and nine with
      the same regimen added with ara-C (Group 2). Ara-C was administered on a 5-day
      schedule as an i.v. continuous infusion at the dose of 150 mg m(-2) per day for
      five consecutive days. During treatment complete remission (CR) was achieved in
      two dogs in Group 1 and in eight dogs in Group 2. CR rate was significantly
      higher in Group 2 (P < 0.01). Median survival was 72.5 days (range 6-174) in
      Group 1 and 243 days (range 73-635) in Group 2. Survival was significantly longer
      in Group 2 (P < 0.001). Both protocols were well tolerated, with a low incidence
      of adverse events. Ara-C added to a VCAA-based protocol appears to be safe and
      beneficial in dogs with stage V lymphoma. Incorporation of the nucleoside
      analogue might be crucial for the development of future therapeutic strategies in
      dogs.

PMID- 19178669
TI  - Description of clinical and pathological findings, treatment and outcome of
      feline large granular lymphocyte lymphoma (1996-2004).
AB  - Feline large granular lymphocyte (LGL) lymphoma is an uncommon, morphologically
      distinct variant of feline lymphoma. Limited information exists in the literature
      regarding pathological and immunohistochemical descriptions, clinical findings,
      treatment and survival times. The purpose of this study was to describe clinical
      features, treatment and outcome in feline LGL lymphoma. Medical records of 45
      cats with LGL lymphoma were retrospectively evaluated. Decreased
      appetite/anorexia, weight loss, lethargy and vomiting were the most commonly
      reported clinical signs. All cats tested for feline leukaemia virus and feline
      immunodeficiency virus infection were negative. The mesenteric lymph nodes and
      small intestine were the most commonly affected organs. One complete response and
      six partial responses were noted in the 23 cats that received chemotherapy as
      their initial treatment. Median survival time for cats that were treated was 57
      days. Based on these results, feline LGL lymphoma appears to be minimally
      responsive to chemotherapy and is associated with a grave prognosis.

PMID- 19178670
TI  - Dose-escalating vinblastine for the treatment of canine mast cell tumour.
AB  - The purpose of this study was to evaluate the short-term adverse events (AEs) in
      dogs with mast cell tumours (MCT) receiving prednisone and dose-escalating
      vinblastine (VBL). Twenty-four dogs were treated with intravenous VBL starting at
      2 mg m(-2) and then escalating in weekly increments to 2.33, 2.67 and 3 mg m(-2).
      AEs were graded using a standardized scoring system. No dogs receiving 2 or 2.33
      mg m(-2) experienced grade 3 or 4 AEs. Among the dogs, 9.5 and 5.9% had grade 3
      or 4 AEs at dosages of 2.67 and 3 mg m(-2), respectively. Serious AEs included
      neutropaenia (n = 3) and vomiting (n = 1), only one of which required
      hospitalization. These data indicate that VBL chemotherapy may be safe to
      administer at higher than the traditional 2 mg m(-2) dosage for dogs with MCT.
      Randomized prospective trials are necessary to establish whether dose escalation
      will translate into improved response rates when compared with the standard 2 mg
      m(-2) dosage.

PMID- 19178671
TI  - Pulmonary fibrosis after high cumulative dose nitrosourea chemotherapy in a cat.
AB  - Small to intermediate cell alimentary lymphoma was diagnosed in a cat after
      abdominal exploratory surgery with no prior history of pulmonary disease. Initial
      response to several chemotherapy regimens was poor, but a long-term remission was
      achieved with CCNU (lomustine) and corticosteroid therapy. After receiving a
      total cumulative CCNU dose of 552 mg m(-2) over 12 months, an acute episode of
      respiratory distress occurred and the cat died. Necropsy identified severe
      diffuse pulmonary fibrosis and no signs of lymphoma. This is the first report of
      pulmonary fibrosis following high cumulative dose nitrosourea chemotherapy in a
      cat.

PMID- 19178672
TI  - Serum vascular endothelial growth factor concentrations and postsurgical outcome
      in dogs with osteosarcoma.
AB  - Vascular endothelial growth factor (VEGF) is a key angiogenic growth factor,
      playing putative roles in both tumour growth and metastasis. The purpose of this
      study was to correlate pretreatment serum concentrations of VEGF in dogs with
      osteosarcoma (OSA) with disease-free interval (DFI) and overall survival (OS).
      Additionally, the effect of serum from dogs with OSA on ex vivo canine
      endothelial cell (EC) growth was determined. Pretreatment platelet-corrected
      serum VEGF levels correlated significantly with DFI. No other examined variable
      predicted outcome. The ability of sera from dogs with OSA to stimulate canine EC
      proliferation did not correlate with VEGF concentration or outcome. These data
      support a role for VEGF in the development or progression of metastatic disease
      in dogs with OSA. The VEGF concentration in tested sera was not a major
      determinant of ex vivo canine EC proliferation in this study.

PMID- 19178673
TI  - Glucose transporter 1 expression in canine osteosarcoma.
AB  - Hypoxia in tumours has been associated with an increased resistance to radiation
      and chemotherapy, and increased metastatic potential. Hypoxia-inducible factor 1
      alpha (HIF-1alpha) is a transcription factor induced by hypoxia. Glucose
      transporter 1 (GLUT-1), a downstream product of HIF-1alpha pathway activation, is
      over-expressed in a variety of human tumours. The purpose of this study was to
      determine if GLUT-1 is expressed in canine osteosarcomas (OSAs) and if the
      expression is related to tumour necrosis and outcome. Immunohistochemistry was
      performed on 44 histologically confirmed OSA tissue samples to assess expression
      of GLUT-1. Of 44 cases, 27 (61%) expressed GLUT-1. There was no statistical
      correlation between GLUT-1 and disease-free interval, survival time or percentage
      of necrosis. As hypothesized, GLUT-1 is present in canine appendicular OSAs. A
      more objective evaluation of GLUT-1 and other proteins in the HIF-1alpha pathway
      may be warranted.

PMID- 19178674
TI  - Identification of survivin, an inhibitor of apoptosis, in canine urinary bladder
      transitional cell carcinoma.
AB  - Survivin, an inhibitor of apoptosis, is overexpressed in human invasive
      transitional cell carcinoma (TCC) of the urinary bladder. Survivin expression in
      canine TCC has not been defined. This study was designed to compare survivin
      expression between canine TCC and normal urinary bladder tissue. Reverse
      transcriptase polymerase chain reaction (PCR) and immunohistochemistry (IHC) were
      performed on fresh-frozen and formalin-fixed tissues, respectively. All TCC
      tissues (n = 6) and 11/22 normal tissues assessed by PCR were positive for
      survivin. This difference was not significant (P = 0.06). With regard to IHC,
      28/41 TCC samples were positive for nuclear survivin, whereas 0/46 normal tissues
      had nuclear immunoreactivity (P < 0.001). Cytoplasmic immunoreactivity did not
      significantly differ between TCC (7/41) and normal tissues (17/46) (P = 0.07). We
      conclude that nuclear survivin is present in canine TCC, but not in normal
      bladder urothelium. Future studies will evaluate the role of nuclear survivin in
      TCC development and as a potential therapeutic target.

PMID- 19178675
TI  - Peripheral washout phenomenon in an animal tumour model: comparison of dynamic
      magnetic resonance imaging using a small molecular contrast medium with
      histology.
AB  - The peripheral washout sign was first described in delayed dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) using a small molecular contrast
      medium in solid lesions of the human breast and liver. It was found to be 100%
      specific for malignant lesions and could therefore potentially be used as an
      additional noninvasive diagnostic tool differentiating malignant from benign
      lesions. The origin of this phenomenon has not yet been explained. The objective
      of this study was to translate the peripheral washout sign as seen in solid
      tumours in delayed DCE-MRI in human onto an animal model for further assessment
      of DCE-MRI characteristics and histological analysis. Small molecular contrast
      medium DCE-MRI was performed over 42 min in experimental colon carcinoma grown
      subcutaneously in rats. Qualitative and quantitative analyses for evaluation of
      presence and characteristics of the peripheral washout sign were accomplished,
      defining four centripetally distributed tumour zones (central, intermediate,
      peripheral and marginal). One hundred per cent of the carcinomas demonstrated a
      peripheral washout sign in DCE-MRI starting at 20 min after bolus injection.
      Histomorphological analysis was performed for tissue classification and
      evaluation of microvasculature. Quantitative analysis revealed different
      enhancement profiles of the four tumour zones. Histology indicated centripetally
      asymmetric vascularization and vascular endothelial growth factor VEGF/VEGF
      receptor 2 expression within the tumour tissue. Thus, peripheral washout sign can
      be translated to an animal model. However, comparison of small molecular contrast
      medium DCE-MRI with histology revealed that histology alone does not explain the
      occurrence of the peripheral washout.

PMID- 19178676
TI  - Morphometrical approach for predicting regional lymph node micrometastatic load
      in canine mast cell tumours: preliminary results.
AB  - Canine cutaneous mast cell tumours (MCTs) have a variable biologic behaviour, and
      accurate staging is necessary to dictate therapy and predict outcome. Regional
      lymph node (RLN) involvement is a relevant prognostic factor. While obvious lymph
      node (LN) metastases are relatively easy to be diagnosed, micrometastatic disease
      recognition is challenging. The main aim of the study was to evaluate the number
      of mast cells (MCs) in the LNs of clinically healthy dogs (n = 4, group 1), dogs
      with inflammatory diseases (n = 31, group 2) and dogs with cutaneous MCT (n = 27,
      group 3), including animals with no RLN metastases (subgroup 3.1), those with
      occasional MCs in RLNs (3.2) and those with obvious RLN metastasis (3.3). MCs
      also were morphometrically evaluated for the following nuclear parameters: mean
      nuclear area (MNA), mean nuclear perimeter (MNP), largest to smallest diameter
      length (LS ratio), mean nuclear form factor and coefficient of variation of
      nuclear area. The average percentages of MCs were 0.0 and 0.01 in groups 1 and 2,
      respectively, and 0.07, 2.4 and 47.1 in subgroup 3.1, 3.2 and 3.3. MNA and MNP
      were significantly higher in subgroup 3.3 than in group 2 (P < 0.05). MNA and MNP
      in subgroup 3.2 suggested the presence of neoplastic MCs; this prediction of
      micrometastatic load correlated with outcome. Analysis of preliminary results
      shows that nuclear morphometry is useful to detect micrometastatic disease in RLN
      of dogs bearing cutaneous MCTs.

PMID- 19178677
TI  - Glycoproteomic profiling of serum peptides in canine lymphoma and transitional
      cell carcinoma.
AB  - Differential expression of fucosylated glycoproteins has been correlated with
      malignancy and metastatic potential in various types of neoplasia. Utilizing
      glycoproteomics techniques, changes in fucosylated serum peptides associated with
      naturally occurring canine lymphoma and transitional cell carcinoma (TCC) have
      been evaluated. In both types of neoplasia, the majority of the fucosylated
      peptides that changed increased with the cancer. In one lymphoma case that was
      examined over the course of the disease, the same fucosylated peptides that
      increased during pre-chemotherapy decreased during post-chemotherapy, and then
      subsequently increased upon recurrence of the lymphoma. When comparing all the
      fucosylated peptides that increased in both types of cancer, there were only two
      peptides in common allowing discrimination between lymphoma and TCC based on
      their peptide profiles. These results emphasize the prospect of glycopeptide
      profiling in proteomics for use in discovering a panel of non-invasive,
      diagnostic or prognostic biomarkers of cancer.

PMID- 19178678
TI  - Preliminary analysis of genomic abnormalities in canine meningiomas.
AB  - Cytogenetic detection of unbalanced genomic aberrations in tumours is a strategy
      for the identification of tumour suppressor genes and oncogenes. When considered
      in concert with clinical data, the approach also represents a means of
      identifying markers of prognosis. In a preliminary investigation of the molecular
      basis of canine meningioma tumorigenesis, we profiled three tumours by
      comparative genomic hybridization. Distinct patterns of sub-chromosomal deletions
      were identified suggesting alternative mechanisms of tumour initiation. The
      deleted chromosomal segments encompass two regions (10q23.1 and 17q22-q23) that
      are syntenic to the chromosomes (22 and 1p) most often deleted in human
      meningiomas. A number of genes associated with DNA repair, cell cycle progression
      and apoptosis are located on both the deleted canine chromosomal segments and the
      syntenic regions deleted in human meningiomas. This study represents the first
      report of chromosomal copy number abnormalities in non-cultured canine brain
      tumour tissue.

PMID- 19178679
TI  - Radiosensitivity of canine osteosarcoma cells transfected with wild-type p53 in
      vitro.
AB  - The p53 gene is one of the important tumour suppressor genes that are involved
      with the cell survival signal pathway. One of the major functions of the p53
      protein is to organize cell cycle regulation and induction of apoptosis for
      cellular genetic stability. It has been documented that more than 50% of all
      human cancers include a p53 mutation. We evaluated the difference in
      radiosensitivity between upregulating the expression of canine wild-type p53
      (cp53) in cultured osteosarcoma (D17) cells and naive D17 cells in vitro. We
      found that upregulating transfected cp53 D17 cells increased their radiation
      sensitivity in vitro, and there was a significant decrease (P < 0.009) in
      survival between cp53-transfected D17 cells and naive D17 cells. In this
      experiment, a p53 enhancement ratio (p53ER) reached approximately 3.0 at high
      doses. The transfected cp53 D17 cells were significantly more radiosensitive at
      all doses evaluated than naive D17 cells, except at 1 Gy where too few data
      points were available. The p53ER increased rapidly at doses less than 4 Gy,
      achieving a maximum of about 3.0 for doses of 4 Gy and above. This study shows
      the enhanced radiosensitivity of the transfected p53 at clinically relevant
      doses.

PMID- 19178680
TI  - Evaluation of P-glycoprotein expression in feline lymphoma and correlation with
      clinical outcome.
AB  - P-glycoprotein (Pgp) is a transmembrane protein pump involved in drug resistance
      in canine and human lymphoma. There are no published clinical studies evaluating
      Pgp expression in feline lymphoma. The purpose of this study is to evaluate the
      level of Pgp expression in feline lymphoma and correlate it with clinical
      outcome. Two human Pgp monoclonal antibodies, C219 and C494, were used to detect
      Pgp expression in tissue samples from 63 cats with lymphoma. Demographic results
      appear comparable to recently published feline lymphoma studies. The Kaplan-Meier
      median remission and survival times were 164 and 571 days, respectively. Fourteen
      cats had positive expression of Pgp using MAb C219, and 40 were positive with
      C494. Variables statistically associated with survival included bone marrow
      involvement, stage, substage, and use of radiation therapy as a part of
      treatment. Pgp expression as assessed by MAb C219 and C494 is not predictive of
      remission or survival time in cats with lymphoma.

PMID- 19178681
TI  - The role of hypoxia in canine cancer.
AB  - Human oncology has clearly demonstrated the existence of hypoxic tumours and the
      problematic nature of those tumours. Hypoxia is a significant problem in the
      treatment of all types of solid tumours and a common reason for treatment
      failure. Hypoxia is a negative prognostic indicator of survival and is correlated
      with the development of metastatic disease. Resistance to radiation therapy and
      chemotherapy can be because of hypoxia. There are two dominant types of hypoxia
      recognized in tumours, static and intermittent. Both types of hypoxia are
      important in terms of resistance. A variety of physiological factors cause
      hypoxia, and in turn, hypoxia can induce genetic and physiological changes. A
      limited number of studies have documented that hypoxia exists in spontaneous
      canine tumours. The knowledge from the human literature of problematic nature of
      hypoxic tumours combined with the rapid growth of veterinary oncology has
      necessitated a better understanding of hypoxia in canine tumours.

PMID- 19178682
TI  - Serum biomarker profiling in cancer studies: a question of standardisation?
AB  - Companion animals are exposed to similar environmental conditions and carcinogens
      as humans. In some animal cancers, there also appears to be the same genetic
      changes associated as in humans. However, little work has been carried out in
      cancer biomarker identification in animals. The recent dramatic advances in
      molecular medicine, genomics, proteomics and translational research will allow
      biomarker identification, which may provide the best strategies for veterinarians
      and clinicians to combat disease by early diagnosis and administration of
      effective treatments. Proteomics may have important applications in cancer
      diagnosis, prognosis and predictive clinical outcome that could directly change
      clinical practice by affecting critical elemen-ts of care and management. This
      review summarizes the advances in proteomics that has propelled us to this
      exciting age of clinical proteomics, and highlights the future work that is
      required for this to become a reality. In this review, we will discuss the
      available proteomic technologies and their limitations, and highlight the key
      areas of research and how they have been used to discover cancer biomarkers. The
      principles described here are equally applicable to human and animal disease, but
      implementation of 'omic' technologies requires stringent guidelines for
      collection of clinical material, the application of analytical techniques and
      interpretation of the data.

PMID- 19178683
TI  - Evaluation of plasma folate and homocysteine concentrations in cats with and
      without oral squamous cell carcinoma.
AB  - Feline oral squamous cell carcinoma (SCC) is a devastating disease with an
      extremely poor long-term prognosis even with aggressive therapy. Folate and
      homocysteine derangements are identified in people diagnosed with head and neck
      SCC. The purpose of this study was to measure plasma folate and homocysteine
      concentrations in cats diagnosed with oral SCC (n = 13) and to compare these
      concentrations with those found in cats diagnosed with other tumour types (n =
      25), cats with oral, non-neoplastic disease (n = 6) and healthy cats (n = 24).
      The median plasma folate concentration in cats diagnosed with oral SCC was 14.7
      ng mL(-1), while the median plasma homocysteine concentration was 2.61 microg mL(
      1). These concentrations did not differ significantly from those of cats in the
      other groups. This suggests that different factors may contribute to the
      pathogenesis of this tumour in cats when compared with people, although
      evaluation of larger numbers of cats may still identify a difference between
      groups.

PMID- 19178684
TI  - A toxicity study of low-dose rate half-body irradiation and chemotherapy in dogs
      with lymphoma.
AB  - Thirteen dogs with previously untreated multicentric lymphoma were enrolled in a
      prospective study investigating the effects of low-dose rate total body
      irradiation (TBI) and chemotherapy. Dogs received either 6 or 8 Gy TBI in half
      body fractions, 2 weeks apart. Toxicity consisted of mild to moderate
      haematological and gastrointestinal (GI) signs. One dog died from treatment
      complications. Anorexia was noted independent of dose. Haematological toxicity
      was more common and more severe after 8 Gy treatment. GI toxicity was more likely
      postcaudal half-body irradiation with 8 Gy. Other than leukotrichia, late effects
      from radiation were not observed. Results indicated that haematological and
      nonhaematological toxicity was dose dependent. However, the protocol was well
      tolerated and treatment intensification using a 2-week inter-radiation interval
      was possible in all dogs treated with 6 Gy. Preliminary survival data for these
      dogs were very encouraging, providing a strong rationale to analyse the efficacy
      of low-dose rate irradiation (LDRI) in canine lymphoma.

PMID- 19178685
TI  - Association of Ki67 index with prognosis for intermediate-grade canine cutaneous
      mast cell tumours.
AB  - Intermediate-grade mast cell tumours (MCT) represent a heterogeneous population
      of tumours. The prognosis for the majority of dogs is excellent following
      surgical excision, but a minority die because of their disease. A previous study
      identified Ki67 expression as a predictor of prognosis in all three grades of
      MCT. The purpose of this study was to validate those results in a new group of
      dogs, with intermediate-grade MCT only. Ki67 immunohistochemistry was performed
      on intermediate-grade MCT from 163 dogs with known outcome. Digital microscopy
      images were taken from each tumour, and an index calculated of Ki67-positive
      cells. Ki67 index as a binary variable with a cut-off value of 1.8% was confirmed
      to be associated with prognosis (hazard ratio = 19.1, P < 0.0001) for this cohort
      of dogs. The 1-year, 2-year and 3-year survival probabilities (with standard
      errors) of 127 dogs with a Ki67 index <or=1.8% were [0.95 (0.024), similar for
      all] and for 36 dogs with a Ki67 index >1.8% were 0.54 (0.100), 0.45 (0.101) and
      0.33 (0.104), respectively.

PMID- 19178687
TI  - Emergency surgery, acute care surgery and the boulevard of broken dreams.

PMID- 19178688
TI  - An Ac/Ds-mediated gene trap system for functional genomics in barley.
AB  - BACKGROUND: Gene trapping is a powerful tool for gene discovery and functional
      genomics in both animals and plants. Upon insertion of the gene trap construct
      into an expressed gene, splice donor and acceptor sites facilitate the generation
      of transcriptional fusions between the flanking sequence and the reporter.
      Consequently, detection of reporter gene expression allows the identification of
      genes based on their expression pattern. Up to now rice is the only cereal crop
      for which gene trap approaches exist. In this study we describe a gene trap
      system in barley (Hordeum vulgare L.) based on the maize transposable elements
      Ac/Ds. RESULTS: We generated gene trap barley lines by crossing Ac transposase
      expressing plants with multiple independent transformants carrying the Ds based
      gene trap construct GTDsB. Upstream of the beta-Glucuronidase start codon GTDsB
      carries splice donor and acceptor sites optimized for monocotyledonous plants.
      DNA blot analysis revealed GTDsB transposition frequencies of 11% and 26% in the
      F1 and F2 generation of gene trap lines and perpetuation of transposition
      activity in later generations. Furthermore, analysis of sequences flanking
      transposed GTDsB elements evidenced preferential insertion into expressed regions
      of the barley genome. We screened leaves, nodes, immature florets, pollinated
      florets, immature grains and seedlings of F2 plants and detected GUS expression
      in 51% (72/141) of the plants. Thus, reporter gene expression was found in 24 of
      the 28 F1 lines tested and in progeny of all GTDsB parental lines. CONCLUSION:
      Due to the frequent transposition of GTDsB and the efficient expression of the
      GUS reporter gene, we conclude that this Ac/Ds-based gene trap system is an
      applicable approach for gene discovery in barley. The successful introduction of
      a gene trap construct optimized for monocots in barley contributes a novel
      functional genomics tool for this cereal crop.

PMID- 19178689
TI  - Muscle Research and Gene Ontology: New standards for improved data integration.
AB  - BACKGROUND: The Gene Ontology Project provides structured controlled vocabularies
      for molecular biology that can be used for the functional annotation of genes and
      gene products. In a collaboration between the Gene Ontology (GO) Consortium and
      the muscle biology community, we have made large-scale additions to the GO
      biological process and cellular component ontologies. The main focus of this
      ontology development work concerns skeletal muscle, with specific consideration
      given to the processes of muscle contraction, plasticity, development, and
      regeneration, and to the sarcomere and membrane-delimited compartments. Our aims
      were to update the existing structure to reflect current knowledge, and to
      resolve, in an accommodating manner, the ambiguity in the language used by the
      community. RESULTS: The updated muscle terminologies have been incorporated into
      the GO. There are now 159 new terms covering critical research areas, and 57
      existing terms have been improved and reorganized to follow their usage in muscle
      literature. CONCLUSION: The revised GO structure should improve the
      interpretation of data from high-throughput (e.g. microarray and proteomic)
      experiments in the area of muscle science and muscle disease. We actively
      encourage community feedback on, and gene product annotation with these new
      terms. Please visit the Muscle Community Annotation Wiki
      http://wiki.geneontology.org/index.php/Muscle_Biology.

PMID- 19178690
TI  - Altering the ribosomal subunit ratio in yeast maximizes recombinant protein
      yield.
AB  - BACKGROUND: The production of high yields of recombinant proteins is an enduring
      bottleneck in the post-genomic sciences that has yet to be addressed in a truly
      rational manner. Typically eukaryotic protein production experiments have relied
      on varying expression construct cassettes such as promoters and tags, or culture
      process parameters such as pH, temperature and aeration to enhance yields. These
      approaches require repeated rounds of trial-and-error optimization and cannot
      provide a mechanistic insight into the biology of recombinant protein production.
      We published an early transcriptome analysis that identified genes implicated in
      successful membrane protein production experiments in yeast. While there has been
      a subsequent explosion in such analyses in a range of production organisms, no
      one has yet exploited the genes identified. The aim of this study was to use the
      results of our previous comparative transcriptome analysis to engineer improved
      yeast strains and thereby gain an understanding of the mechanisms involved in
      high-yielding protein production hosts. RESULTS: We show that tuning BMS1
      transcript levels in a doxycycline-dependent manner resulted in optimized yields
      of functional membrane and soluble protein targets. Online flow microcalorimetry
      demonstrated that there had been a substantial metabolic change to cells cultured
      under high-yielding conditions, and in particular that high yielding cells were
      more metabolically efficient. Polysome profiling showed that the key molecular
      event contributing to this metabolically efficient, high-yielding phenotype is a
      perturbation of the ratio of 60S to 40S ribosomal subunits from approximately 1:1
      to 2:1, and correspondingly of 25S:18S ratios from 2:1 to 3:1. This result is
      consistent with the role of the gene product of BMS1 in ribosome biogenesis.
      CONCLUSION: This work demonstrates the power of a rational approach to
      recombinant protein production by using the results of transcriptome analysis to
      engineer improved strains, thereby revealing the underlying biological events
      involved.

PMID- 19178692
TI  - Mitral regurgitation due to caseous calcification of the mitral annulus: two case
      reports.
AB  - Caseous calcification is a rare variant of mitral annular calcification,
      occurring in about 0.06% of echocardiographic studies performed. It is usually a
      benign lesion, but it should be differentiated by abscess and tumors.
      Echocardiography is the most sensitive method to identify caseous calcification
      which appears typically as a round, calcified mass with an echo-lucent, liquid
      like inner part.

PMID- 19178691
TI  - Novel polymorphism of interleukin-18 associated with greater inflammation after
      cardiac surgery.
AB  - INTRODUCTION: Interleukin (IL)-18 is a key modulator of the cytokine response
      that leads to organ dysfunction and prolonged intensive care unit (ICU) stay
      after cardiopulmonary bypass surgery. We hypothesised that variation in the pro
      inflammatory gene IL-18 is associated with adverse clinical outcome because of a
      more intense inflammatory response. METHODS: Haplotypes of the IL-18 gene were
      inferred from genotypes of 23 Coriell Registry subjects. Four haplotype tag
      single nucleotide polymorphisms (-607 C/A, -137 G/C, 8148 C/T and 9545 T/G)
      identified four major haplotype clades. These polymorphisms were genotyped in 658
      Caucasian patients undergoing cardiopulmonary bypass surgery. Clinical phenotypes
      were collected by retrospective chart review. RESULTS: Patients homozygous for
      the T allele of the 9545 T/G polymorphism had an increased occurrence of
      prolonged ICU stay (6.8% for TT genotype versus 2.7% for GG or GT genotype; p =
      0.015). Patients homozygous for the T allele also had increased occurrence of low
      systemic vascular resistance index (62%) compared with the GG and GT genotypes
      (53%; p = 0.045). Patients homozygous for the T allele had increased serum IL-18
      concentrations 24 hours post-surgery (p = 0.018), increased pro-inflammatory
      tumour necrosis factor alpha concentrations (p = 0.014) and decreased anti
      inflammatory serum IL-10 concentrations (p = 0.018) 24 hours post-surgery.
      CONCLUSIONS: The TT genotype of the IL-18 9545 T/G polymorphism is associated
      with an increased occurrence of prolonged ICU stay post-surgery and greater post
      surgical inflammation. These results may be explained by greater serum IL-18,
      leading to greater pro-versus anti-inflammatory cytokine expression.

PMID- 19178693
TI  - Hemorrhagic cerebral infarction in carbon monoxide poisoning: a case report.
AB  - INTRODUCTION: Almost every known central neurological syndrome has been reported
      as a complication of carbon monoxide poisoning. Hemorrhagic infarct has rarely
      been considered as an early manifestation of carbon monoxide poisoning. A case of
      cerebral hemorrhagic infarction is presented. Typical findings, neuropathology
      and the role of vascular injury are described. CASE PRESENTATION: The symptoms
      and clinical course of acute poisoning with carbon monoxide in a 7-year-old boy
      are described. To evaluate the possible causes, a brain computed tomography (CT)
      was performed that showed thick clot in the left medial temporal and parasellar
      area, left sylvian fissure (acute intravascular thrombus) accompanied by left
      diffuse frontotemporal hypodensity and midline shift. Four-vessel digital
      subtraction angiography two weeks after intoxication was not indicative of any
      vascular lesion. CONCLUSION: Hemorrhagic infarction is a rare presentation of
      carbon monoxide poisoning. When found in a child, in addition to conservative
      treatment to reduce the neurocognitive squeal, other probable causes should be
      ruled out.

PMID- 19178694
TI  - Idiopathic autoimmune hemolytic anemia due to lecithin overdose: a case report.
AB  - INTRODUCTION: Idiopathic Autoimmune Hemolytic Anemia is a potentially fatal
      condition which requires prompt and potent treatment. Diagnosis of idiopathic
      autoimmune hemolytic anemia requires both serologic evidence of autoantibody
      presence and hemolysis. Although most of the times it is considered idiopathic,
      several underlying causes have been identified, like autoimmune and connective
      tissue diseases, viral infections, drugs or hyper function of the immune system.
      To our knowledge, this is the first case in the international literature
      describing lecithin-induced autoimmune hemolytic anemia. CASE PRESENTATION: This
      case report is to highlight a rare but dangerous adverse reaction to overdose of
      lecithin. A 38 year old white female from Greece, presented to our emergency room
      with progressive fatigue over a period of ten days and icteric discoloration of
      her skin and conjunctiva. The patient had been taking lecithin supplements (1200
      mg, 3 capsules a day) over a period of ten days for weight loss. She reports that
      the last 3 days, prior to the examination, she took 5 capsules/day, so that the
      supplement would take effect more rapidly. Her past medical, social and family
      history showed no disturbance. Relatives of the patient were requested to submit
      any blood-tests taken over a period of 20 days prior to the onset of symptoms
      caused by Lecithin. All tests proved that all functions were within normal scale.
      Her physical examination revealed pallor and jaundice without palpable
      hepatosplenomegaly. Blood biochemistry tests showed total bilirubin 7.5 mg/dl,
      with indirect bilirubin 6.4 mg/dl and complete blood count showed hemoglobin 7.6
      g/dl with blood levels 21.4%. CONCLUSION: In every case of idiopathic autoimmune
      hemolytic anemia the administration of pharmaceutical substances should always be
      examined, except for the standard reasons that cause it. In this case the cause
      of hemolysis was attributed to the excessive intake of lecithin capsules for the
      loss of body weight. It is important that clinicians and immunologists are aware
      of this adverse effect.

PMID- 19178695
TI  - Hughes-Stovin syndrome: a case report and review of the literature.
AB  - BACKGROUND: Hughes-Stovin syndrome is a rare entity. The aetiology of Hughes
      Stovin syndrome is still unknown and the natural course of the illness is usually
      fatal; however it is supposed to be a clinical variant manifestation of Behcet
      disease. CASE PRESENTATION: We report the case of an 18 years old, greek male
      patient with Hughes-Stovin syndrome, who initially presented with deep vein
      thrombosis. There were no findings consistent with Behcet disease and the
      haemoptysis was treated successfully with methylprednisolone. Pathogenesis,
      imaging investigation and treatment of this syndrome are also briefly discussed.
      CONCLUSION: In young men presenting with venous thrombosis as revealed on imaging
      examination, with platelet count and coagulation tests within normal and
      hemoptysis the eventuality of Hughes-Stovin syndrome is to be considered.

PMID- 19178696
TI  - A diagnostic dilemma: a case report.
AB  - BACKGROUND: A seventy nine year old lady presented with acute bilateral foot drop
      and paraesthesia of her lower limbs as a presenting feature of Wegener's
      Granulomatosis (WG). CASE PRESENTATION: There was no evidence of pulmonary
      involvement and her renal function was normal. WG can masquerade as very diverse
      pathology. It is recognised that neuropathy can occur early and often in the
      absence of more classical pulmonary and renal findings, often resulting in a
      delay in diagnosis. CONCLUSION: Anti-neutrophil cytoplasmic antibody (ANCA)
      testing was particularly useful in this case permitting early diagnosis.

PMID- 19178697
TI  - Export of recombinant proteins in Escherichia coli using ABC transporter with an
      attached lipase ABC transporter recognition domain (LARD).
AB  - BACKGROUND: ATP binding cassette (ABC) transporter secretes the protein through
      inner and outer membranes simultaneously in gram negative bacteria. Thermostable
      lipase (TliA) of Pseudomonas fluorescens SIK W1 is secreted through the ABC
      transporter. TliA has four glycine-rich repeats (GGXGXD) in its C-terminus, which
      appear in many ABC transporter-secreted proteins. From a homology model of TliA
      derived from the structure of P. aeruginosa alkaline protease (AprA), lipase ABC
      transporter domains (LARDs) were designed for the secretion of fusion proteins.
      RESULTS: The LARDs included four glycine-rich repeats comprising a beta-roll
      structure, and were added to the C-terminus of test proteins. Either Pro-Gly
      linker or Factor Xa site was added between fusion proteins and LARDs. We attached
      different length of LARDs such as LARD0, LARD1 or whole TliA (the longest LARD)
      to three types of proteins; green fluorescent protein (GFP), epidermal growth
      factor (EGF) and cytoplasmic transduction peptide (CTP). These fusion proteins
      were expressed in Escherichia coli together with ABC transporter of either P.
      fluorescens or Erwinia chrysanthemi. Export of fusion proteins with the whole
      TliA through the ABC transporter was evident on the basis of lipase enzymatic
      activity. Upon supplementation of E. coli with ABC transporter, GFP-LARDs and EGF
      LARDs were excreted into the culture supernatant. CONCLUSION: The LARDs or whole
      TliA were attached to C-termini of model proteins and enabled the export of the
      model proteins such as GFP and EGF in E. coli supplemented with ABC transporter.
      These results open the possibility for the extracellular production of
      recombinant proteins in Pseudomonas using LARDs or TliA as a C-terminal signal
      sequence.

PMID- 19178698
TI  - From arginine methylation to ADMA: a novel mechanism with therapeutic potential
      in chronic lung diseases.
AB  - Protein arginine methylation is a novel posttranslational modification regulating
      a diversity of cellular processes, including protein-protein interaction, signal
      transduction, or histone function. It has recently been shown to be dysregulated
      in chronic renal, vascular, and pulmonary diseases, and metabolic products
      originating from protein arginine methylation have been suggested to serve as
      biomarkers in cardiovascular and pulmonary diseases. Protein arginine methylation
      is performed by a class of enzymes called protein arginine methyltransferases
      (PRMT), which specifically methylate protein-incorporated arginine residues to
      generate protein-incorporated monomethylarginine (MMA), symmetric
      dimethylarginine (SDMA), or asymmetric dimethylarginine (ADMA). Upon proteolytic
      cleavage of arginine-methylated proteins, free intracellular MMA, SDMA, or ADMA
      is generated, which, upon secretion into the extracellular space (including
      plasma), directly affects the methylarginine concentration in the plasma. Free
      methylarginines are cleared from the body by renal excretion or hepatic
      metabolism. In addition, MMA and ADMA, but not SDMA, can be degraded via a class
      of intracellular enzymes called dimethylarginine dimethylaminohydrolases (DDAH).
      ADMA and MMA are endogenous inhibitors of nitric oxide synthases (NOS) and ADMA
      has been suggested to serve as a biomarker of endothelial dysfunction in
      cardiovascular diseases. This view has now been extended to the idea that, in
      addition to serum ADMA, the amount of free, as well as protein-incorporated,
      intracellular ADMA influences pulmonary cell function and determines the
      development of chronic lung diseases, including pulmonary arterial hypertension
      (PAH) or pulmonary fibrosis. This review will present and discuss the recent
      findings of dysregulated arginine methylation in chronic lung disease. We will
      highlight novel directions for future investigations evaluating the functional
      contribution of arginine methylation in lung homeostasis and disease with the
      outlook that modifying PRMT or DDAH activity presents a novel therapeutic option
      for the treatment of chronic lung disease.

PMID- 19178700
TI  - Repeatability of regional myocardial blood flow calculation in 82Rb PET imaging.
AB  - BACKGROUND: We evaluated the repeatability of the calculation of myocardial blood
      flow (MBF) at rest and pharmacological stress, and calculated the coronary flow
      reserve (CFR) utilizing 82Rb PET imaging. The aim of the research was to prove
      high repeatability for global MBF and CFR values and good repeatability for
      regional MBF and CFR values. The results will have significant impact on cardiac
      PET imaging in terms of making it more affordable and increasing its use.
      METHODS: 12 normal volunteers were imaged at rest and during pharmacological
      stress, with 2220 MBq of 82Rb each. A GE Advance PET system was used to acquire
      dynamic 50-frame studies. MBF was calculated with a 2-compartmental model using a
      modified PMOD program (PMOD; University Hospital Zurich, Zurich, Switzerland).
      Two differential equations, describing a 2-compartmental model, were solved by
      numerical integration and using Levenberg-Marquardt's method for fitting data.
      The PMOD program defines 16 standard segments and calculates myocardial flow for
      each segment, as well as average septal, anterior, lateral, inferior and global
      flow. Repeatability was evaluated according to the method of Bland and Altman.
      RESULTS: Global rest and stress MBF, as well as global CFR, showed very good
      repeatability. No significant differences were found between the paired resting
      global MBF (0.63 +/- 0.13 vs. 0.64 +/- 0.13 mL/min/g; mean difference, -1.0% +/-
      2.6%) and the stress global MBF (1.37 +/- 0.23 vs. 1.37 +/- 0.24; mean
      difference, 0.1% +/- 2.3%). Global CFR was highly reproducible (2.25 +/- 0.56 vs.
      2.22 +/- 0.54, P = not statistically significant; mean difference, 1.3% +/-
      14.3%). Repeatability coefficients for global rest MBF were 0.033 (5.2%) and
      stress MBF 0.062 (4.5%) mL/min/g. Regional rest and stress MBF and CFR have shown
      good reproducibility. The average per sector repeatability coefficients for rest
      MBF were 0.056 (8.5%) and stress MBF 0.089 (6.3%) mL/min/g, and average
      repeatability coefficient for CFR was 0.25 (10.6%). CONCLUSION: The results of
      the study show that software calculation of MBF and CFR with 82Rb myocardial PET
      imaging is highly repeatable for global values and has good repeatability for
      regional values.

PMID- 19178699
TI  - Global analysis of alternative splicing regulation by insulin and wingless
      signaling in Drosophila cells.
AB  - BACKGROUND: Despite the prevalence and biological relevance of both signaling
      pathways and alternative pre-mRNA splicing, our knowledge of how intracellular
      signaling impacts on alternative splicing regulation remains fragmentary. We
      report a genome-wide analysis using splicing-sensitive microarrays of changes in
      alternative splicing induced by activation of two distinct signaling pathways,
      insulin and wingless, in Drosophila cells in culture. RESULTS: Alternative
      splicing changes induced by insulin affect more than 150 genes and more than 50
      genes are regulated by wingless activation. About 40% of the genes showing
      changes in alternative splicing also show regulation of mRNA levels, suggesting
      distinct but also significantly overlapping programs of transcriptional and post
      transcriptional regulation. Distinct functional sets of genes are regulated by
      each pathway and, remarkably, a significant overlap is observed between
      functional categories of genes regulated transcriptionally and at the level of
      alternative splicing. Functions related to carbohydrate metabolism and cellular
      signaling are enriched among genes regulated by insulin and wingless,
      respectively. Computational searches identify pathway-specific sequence motifs
      enriched near regulated 5' splice sites. CONCLUSIONS: Taken together, our data
      indicate that signaling cascades trigger pathway-specific and biologically
      coherent regulatory programs of alternative splicing regulation. They also reveal
      that alternative splicing can provide a novel molecular mechanism for crosstalk
      between different signaling pathways.

PMID- 19178701
TI  - COPD exacerbation: lost in translation.
AB  - The introduction and acceptance of a standard definition for exacerbations of
      COPD can be helpful in prompt diagnosis and management of these events. The
      latest GOLD executive committee recognised this necessity and it has now included
      a definition of exacerbation in the guidelines for COPD which is an important
      step forward in the management of the disease. This definition is pragmatic and
      compromises the different approaches for exacerbation. However, the inclusion of
      the "healthcare utilisation" approach (".. may warrant a change in regular
      medication") in the definition may introduce in the diagnosis of exacerbation
      factors related to the access to health care services which may not be related to
      the underlying pathophysiological process which characterizes exacerbations. It
      should be also noted that the aetiology of COPD exacerbations has not yet been
      included in the current definition. In this respect, the definition does not
      acknowledge the fact that many patients with COPD may suffer from additional
      conditions (i.e. congestive cardiac failure or pulmonary embolism) that can
      masquerade as exacerbations but they should not be considered as causes of them.
      The authors therefore suggest that an inclusion of the etiologic factors of COPD
      exacerbations in the definition. Moreover, COPD exacerbations are characterized
      by increased airway and systemic inflammation and significant deterioration in
      lung function. These fundamental aspects should be accounted in
      diagnosis/definition of exacerbations. This could be done by the introduction of
      a "laboratory" marker in the diagnosis of these acute events. The authors
      acknowledge that the use of a test or a biomarker in the diagnosis of
      exacerbations meets certain difficulties related to performing lung function
      tests or to sampling during exacerbations. However, the introduction of a test
      that reflects airway or systemic inflammation in the diagnosis of exacerbations
      might be another step forward in the management of COPD.

PMID- 19178702
TI  - Asthma caused by occupational exposures is common - a systematic analysis of
      estimates of the population-attributable fraction.
AB  - BACKGROUND: The aim of this paper is to highlight emerging data on occupational
      attributable risk in asthma. Despite well documented outbreaks of disease and the
      recognition of numerous specific causal agents, occupational exposures previously
      had been relegated a fairly minor role relative to other causes of adult onset
      asthma. In recent years there has been a growing recognition of the potential
      importance of asthma induced by work-related exposures METHODS: We searched Pub
      Med from June 1999 through December 2007. We identified six longitudinal general
      population-based studies; three case-control studies and eight cross-sectional
      analyses from seven general population-based samples. For an integrated analysis
      we added ten estimates prior to 1999 included in a previous review. RESULTS: The
      longitudinal studies indicate that 16.3% of all adult-onset asthma is caused by
      occupational exposures. In an overall synthesis of all included studies the
      overall median PAR value was 17.6%. CONCLUSION: Clinicians should consider the
      occupational history when evaluating patients in working age who have asthma. At
      a societal level, these findings underscore the need for further preventive
      action to reduce the occupational exposures to asthma-causing agents.

PMID- 19178703
TI  - Reproductive tract infections in women seeking abortion in Vietnam.
AB  - BACKGROUND: Women requesting abortion are at increased risk of developing RTI
      complications. However, RTI control in many resource-poor countries including
      Vietnam have been faced with logistical and methodological problems due to lack
      of standardized definitions of RTIs, lack of well-validated diagnostic criteria,
      lack of accurate laboratory tests, and lack of diagnostic equipment and skills.
      This article investigates the prevalence of RTIs among Vietnamese abortion
      seeking women, to evaluate the available diagnostic techniques, and to assess
      antibiotic resistance among aetiological agents of RTI. METHOD: The study was
      conducted in Phu-San hospital (PSH) from December 2003 through April 2004 among
      748 abortion clients. A structured questionnaire was used to collect data on
      socio-economic and reproductive characteristics. Specimens were collected for
      laboratory analyses of chlamydia, gonorrhoea, trichomoniasis, vaginal candidiasis
      (VC), bacterial vaginosis (BV) and syphilis. To assess the validity of the
      obtained results, the study was repeated among 100 women and the duplicate
      samples were analysed at PSH and Copenhagen University Hospital (CUH). RESULTS:
      In all 54% of the women were diagnosed as having an RTI, including 3.3% with
      sexually transmitted infections. Endogenous infections were most prevalent (VC
      34% and BV 12%) followed by chlamydia (1.3%) and trichomoniasis (0.7%). The
      sensitivity of culture for VC and BV was 30% and 88%, respectively, when tests in
      PSH were measured against tests in CUH. Antibiotic resistance was common among
      bacterial isolates. CONCLUSION: RTIs are common among women seeking abortion. The
      presence of RTIs is associated with an increased risk of developing iatrogenic
      infections, routine administration of prophylactic antibiotic to all women
      undergoing abortion should be considered. However, the choice of routine
      prophylactic antibiotics should be based on relevant surveillance data of
      antibiotic resistance. Moreover, since the accuracy of diagnosis is doubtful and
      to address the problem of under-diagnosed and treated RTIs new investment in
      diagnostic facilities with simple performed microscopy or improved rapid tests
      should also be taken into consideration.

PMID- 19178704
TI  - Enterococcal surface protein Esp is not essential for cell adhesion and
      intestinal colonization of Enterococcus faecium in mice.
AB  - BACKGROUND: Enterococcus faecium has globally emerged as a cause of hospital
      acquired infections with high colonization rates in hospitalized patients. The
      enterococcal surface protein Esp, identified as a potential virulence factor, is
      specifically linked to nosocomial clonal lineages that are genetically distinct
      from indigenous E. faecium strains. To investigate whether Esp facilitates
      bacterial adherence and intestinal colonization of E. faecium, we used human
      colorectal adenocarcinoma cells (Caco-2 cells) and an experimental colonization
      model in mice. RESULTS: No differences in adherence to Caco-2 cells were found
      between an Esp expressing strain of E. faecium (E1162) and its isogenic Esp
      deficient mutant (E1162Deltaesp). Mice, kept under ceftriaxone treatment, were
      inoculated orally with either E1162, E1162Deltaesp or both strains
      simultaneously. Both E1162 and E1162Deltaesp were able to colonize the murine
      intestines with high and comparable numbers. No differences were found in the
      contents of cecum and colon. Both E1162 and E1162Deltaesp were able to
      translocate to the mesenteric lymph nodes. CONCLUSION: These results suggest that
      Esp is not essential for Caco-2 cell adherence and intestinal colonization or
      translocation of E. faecium in mice.

PMID- 19178705
TI  - Mechanism of protonophores-mediated induction of heat-shock response in
      Escherichia coli.
AB  - BACKGROUND: Protonophores are the agents that dissipate the proton-motive-force
      (PMF) across E. coli plasma membrane. As the PMF is known to be an energy source
      for the translocation of membrane and periplasmic proteins after their initial
      syntheses in cell cytoplasm, protonophores therefore inhibit the translocation
      phenomenon. In addition, protonophores also induce heat-shock-like stress
      response in E. coli cell. In this study, our motivation was to investigate that
      how the protonophores-mediated phenomena like inhibition of protein translocation
      and induction of heat-shock proteins in E. coli were correlated. RESULTS:
      Induction of heat-shock-like response in E. coli attained the maximum level after
      about 20 minutes of cell growth in the presence of a protonophore like carbonyl
      cyanide m-chloro phenylhydrazone (CCCP) or 2, 4-dinitrophenol (DNP). With
      induction, cellular level of the heat-shock regulator protein sigma-32 also
      increased. The increase in sigma-32 level was resulted solely from its
      stabilization, not from its increased synthesis. On the other hand, the
      protonophores inhibited the translocation of the periplasmic protein alkaline
      phosphatase (AP), resulting its accumulation in cell cytosol partly in aggregated
      and partly in dispersed form. On further cell growth, after withdrawal of the
      protonophores, the previously accumulated AP could not be translocated out;
      instead the AP-aggregate had been degraded perhaps by an induced heat-shock
      protease ClpP. Moreover, the non-translocated AP formed binary complex with the
      induced heat-shock chaperone DnaK and the excess cellular concentration of DnaK
      disallowed the induction of heat-shock response by the protonophores. CONCLUSION:
      Our experimental results suggested that the protonophores-mediated accumulation
      and aggregation of membrane proteins (like AP) in cell cytosol had signaled the
      induction of heat-shock proteins in E. coli and the non-translocated protein
      aggregates were possibly degraded by an induced heat-shock protease ClpP.
      Moreover, the induction of heat-shock response occurred by the stabilization of
      sigma-32. As, normally the DnaK-bound sigma-32 was known to be degraded by the
      heat-shock protease FtsH, our experimental results further suggested that the
      engagement of DnaK with the non-translocated proteins (like AP) had made the
      sigma-32 free and stable.

PMID- 19178707
TI  - An Entry/Gateway cloning system for general expression of genes with molecular
      tags in Drosophila melanogaster.
AB  - BACKGROUND: Tagged fusion proteins are priceless tools for monitoring the
      activities of biomolecules in living cells. However, over-expression of fusion
      proteins sometimes leads to the unwanted lethality or developmental defects.
      Therefore, vectors that can express tagged proteins at physiological levels are
      desirable tools for studying dosage-sensitive proteins. We developed a set of
      Entry/Gateway vectors for expressing fluorescent fusion proteins in Drosophila
      melanogaster. The vectors were used to generate fluorescent CP190 which is a
      component of the gypsy chromatin insulator. We used the fluorescent CP190 to
      study the dynamic movement of related chromatin insulators in living cells.
      RESULTS: The Entry/Gateway system is a timesaving technique for quickly
      generating expression constructs of tagged fusion proteins. We described in this
      study an Entry/Gateway based system, which includes six P-element destination
      vectors (P-DEST) for expressing tagged proteins (eGFP, mRFP, or myc) in
      Drosophila melanogaster and a TA-based cloning vector for generating entry clones
      from unstable DNA sequences. We used the P-DEST vectors to express fluorecent
      CP190 at tolerable levels. Expression of CP190 using the UAS/Gal4 system,
      instead, led to either lethality or underdeveloped tissues. The expressed eGFP-
      or mRFP-tagged CP190 proteins are fully functional and rescued the lethality of
      the homozygous CP190 mutation. We visualized a wide range of CP190 distribution
      patterns in living cell nuclei, from thousands of tiny particles to less than ten
      giant ones, which likely reflects diverse organization of higher-order chromatin
      structures. We also visualized the fusion of multiple smaller insulator bodies
      into larger aggregates in living cells, which is likely reflective of the dynamic
      activities of reorganization of chromatin in living nuclei. CONCLUSION: We have
      developed an efficient cloning system for expressing dosage-sensitive proteins in
      Drosophila melanogaster. This system successfully expresses functional
      fluorescent CP190 fusion proteins. The fluorescent CP190 proteins exist in
      insulator bodies of various numbers and sizes among cells from multiple living
      tissues. Furthermore, live imaging of the movements of these fluorescent-tagged
      proteins suggests that the assembly and disassembly of insulator bodies are
      normal activities in living cells and may be directed for regulating
      transcription.

PMID- 19178706
TI  - Alcohol and cannabis use as risk factors for injury--a case-crossover analysis in
      a Swiss hospital emergency department.
AB  - BACKGROUND: There is sufficient and consistent evidence that alcohol use is a
      causal risk factor for injury. For cannabis use, however, there is conflicting
      evidence; a detrimental dose-response effect of cannabis use on psychomotor and
      other relevant skills has been found in experimental laboratory studies, while a
      protective effect of cannabis use has also been found in epidemiological studies.
      METHODS: Implementation of a case-crossover design study, with a representative
      sample of injured patients (N = 486; 332 men; 154 women) from the Emergency
      Department (ED) of the Lausanne University Hospital, which received treatment for
      different categories of injuries of varying aetiology. RESULTS: Alcohol use in
      the six hours prior to injury was associated with a relative risk of 3.00 (C.I.:
      1.78, 5.04) compared with no alcohol use, a dose-response relationship also was
      found. Cannabis use was inversely related to risk of injury (RR: 0.33; C.I.:
      0.12, 0.92), also in a dose-response like manner. However, the sample size for
      people who had used cannabis was small. Simultaneous use of alcohol and cannabis
      did not show significantly elevated risk. CONCLUSION: The most surprising result
      of our study was the inverse relationship between cannabis use and injury.
      Possible explanations and underlying mechanisms, such as use in safer
      environments or more compensatory behavior among cannabis users, were discussed.

PMID- 19178708
TI  - Serum 25-hydroxyvitamin D is not related to cardiac natriuretic peptide in
      nulliparous and lactating women.
AB  - BACKGROUND: Vitamin D deficiency is associated with heightened risk of
      cardiovascular disease. Potential mechanisms include involvement of vitamin D in
      regulation of renin-angiotensin system and manufacture and secretion of cardiac
      natriuretic peptides. Our aim was to document relationships between 25
      hydroxyvitamin [25(OH)D] and N-terminal pro B-type natriuretic peptide (NT
      proBNP) and plasma renin activity (PRA) levels and to document the effect of
      vitamin D administration on NT-proBNP and PRA levels in vitamin D deficient
      subjects. METHODS: Serum 25(OH)D, parathyroid hormone (PTH), plasma or serum NT
      proBNP and PRA levels were measured at baseline in nulliparous and lactating
      women and after 2 months of oral vitamin D2 (2,000 IU/day or 60,000 IU/month)
      supplementation to lactating women. RESULTS: Baseline levels of 25(OH)D were low
      (<50 nmol/L) in most women whereas PRA and NT-proBNP levels were within the
      normal range. There were no significant correlations between baseline 25(OH)D or
      PTH with NT-proBNP and PRA. Vitamin D administration over a 2-month period in
      lactating women was associated with a decline in NT-proBNP (by 9.1 +/- 2.0
      pmol/L; p < 0.001) and PRA (by 0.32 +/- 0.17 nmol/L/hr; p = 0.064). However,
      there were no significant correlations between the changes from baseline in
      25(OH)D and either NT-proBNP (r = -0.04, p = 0.8) or PRA (r = -0.04, p = 0.8).
      CONCLUSION: We found no significant correlations between 25(OH)D or PTH with NT
      proBNP and PRA in vitamin D deficient women. Further information is required to
      clarify the effects of vitamin D administration on cardiac structure and
      function.

PMID- 19178709
TI  - A wakeboarding injury presented as acute carpal syndrome and median nerve
      contusion after wrist strangulation: a case report.
AB  - BACKGROUND: We present a case of combined median nerve contusion with immediate
      loss of sensation after the strangulation with a wakeboarding rope and prolonged
      referral to our department 72 hours after the injury accompanied by an acute
      carpal tunnel syndrome with immediate relief of numbness of a significant
      proportion of the median nerve following surgical decompression. CASE
      PRESENTATION: The palmar branch of the median nerve was surrounded by a
      significant haematoma in addition to the strangulation damage caused by its more
      superficial location in contrast to the median nerve. CONCLUSION: In case of
      acute median neuropathy, urgent surgical intervention with exploration,
      decompression of both, the median nerve and the superficial branch of the median
      nerve, accompanied by compartment measurements of the forearm should be performed
      to regain or re-establish neurological integrity.

PMID- 19178710
TI  - How to misuse echo contrast.
AB  - BACKGROUND: Primary intracardiac tumours are rare, there are however several
      entities that can mimic tumours. Contrast echocardiography has been suggested to
      aid the differentiation of various suspected masses. We present a case where
      transthoracic echocardiography completely misdiagnosed a left atrial mass, partly
      due to use of echo contrast. CASE PRESENTATION: An 80 year-old woman was referred
      for transthoracic echocardiography because of one-month duration of worsening of
      dyspnoea. Transthoracic echocardiography displayed a large echodense mass in the
      left atrium. Intravenous injection of contrast (SonoVue, Bracco Inc., It)
      indicated contrast-enhancement of the structure, suggesting tumour.
      Transesophageal echocardiography revealed, however, a completely normal finding
      in the left atrium. Subsequent gastroscopy examination showed a hiatal hernia.
      CONCLUSION: It is noteworthy that the transthoracic echocardiographic exam
      completely misdiagnosed what seemed like a left atrial mass, which in part was an
      effect of the use of echo contrast. This example highlights that liberal use of
      transoesophageal echocardiography is often warranted if optimal display of
      cardiac structures is desired.

PMID- 19178711
TI  - Retention of work capacity after coronary artery bypass grafting. A 10-year
      follow-up study.

PMID- 19178712
TI  - Impact of genotyping errors on the type I error rate and the power of haplotype
      based association methods.
AB  - BACKGROUND: We investigated the influence of genotyping errors on the type I
      error rate and empirical power of two haplotype based association methods applied
      to candidate regions. We compared the performance of the Mantel Statistic Using
      Haplotype Sharing and the haplotype frequency based score test with that of the
      Armitage trend test.Our study is based on 1000 replication of simulated case
      control data settings with 500 cases and 500 controls, respectively. One of the
      examined markers was set to be the disease locus with a simulated odds ratio of
      3. Differential and non-differential genotyping errors were introduced following
      a misclassification model with varying mean error rates per locus in the range of
      0.2% to 15.6%. RESULTS: We found that the type I error rate of all three test
      statistics hold the nominal significance level in the presence of non
      differential genotyping errors and low error rates. For high and differential
      error rates, the type I error rate of all three test statistics was inflated,
      even when genetic markers not in Hardy-Weinberg Equilibrium were removed. The
      empirical power of all three association test statistics remained high at around
      89% to 94% when genotyping error rates were low, but decreased to 48% to 80% for
      high and non-differential genotyping error rates. CONCLUSION: Currently realistic
      genotyping error rates for candidate gene analysis (mean error rate per locus of
      0.2%) pose no significant problem for the type I error rate as well as the power
      of all three investigated test statistics.

PMID- 19178713
TI  - Genome-wide analysis of chimpanzee genes with premature termination codons.
AB  - BACKGROUND: Premature termination codons (PTCs) cause mRNA degradation or a
      truncated protein and thereby contribute to the transcriptome and proteome
      divergence between species. Here we present the first genome-wide study of PTCs
      in the chimpanzee. By comparing the human and chimpanzee genome sequences we
      identify and characterize genes with PTCs, in order to understand the
      contribution of these mutations to the transcriptome diversity between the
      species. RESULTS: We have studied a total of 13,487 human-chimpanzee gene pairs
      and found that ~8% were affected by PTCs in the chimpanzee. A majority
      (764/1,109) of PTCs were caused by insertions or deletions and the remaining part
      was caused by substitutions. The distribution of PTC genes varied between
      chromosomes, with Y having the highest proportion. Furthermore, the density of
      PTC genes varied on a megabasepair scale within chromosomes and we found the
      density to be correlated both with indel divergence and proximity to the
      telomere. Within genes, PTCs were more common close to the 5' and 3' ends of the
      amino acid sequence. Gene Ontology classification revealed that olfactory
      receptor genes were over represented among the PTC genes. CONCLUSION: Our results
      showed that the density of PTC genes fluctuated across the genome depending on
      the local genomic context. PTCs were preferentially located in the terminal parts
      of the transcript, which generally have a lower frequency of functional domains,
      indicating that selection was operating against PTCs at sites central to protein
      function. The enrichment of GO terms associated with olfaction suggests that PTCs
      may have influenced the difference in the repertoire of olfactory genes between
      humans and chimpanzees. In summary, 8% of the chimpanzee genes were affected by
      PTCs and this type of variation is likely to have an important effect on the
      transcript and proteomic divergence between humans and chimpanzees.

PMID- 19178714
TI  - Symptomatic intracranial abscess after treating lower cervical spine fracture
      with halo vest: a case report and review of literature.
AB  - We present the case of a nineteen year old male, who sustained a fracture of
      anterior-superior surface of C7, combined with anterior subluxation at the level
      of C6-C7 vertebrae. After x-ray and CT examination, he was treated conservatively
      by a Halo-vest. After mobilization, the patient was discharged from the hospital
      with instructions to visit the outpatient's clinic at regular bases.Despite of
      our instructions, he did not attend the regular follow-up and, three months
      later, he visited the emergencies complaining of pin loosening and serious
      headaches. He was admitted to the clinic in order to perform blood tests and new
      radiological control. During the first day, high fever (over 38,5 degrees C) was
      added to his symptoms. Blood exams were indicative of inflammation. Further
      investigation with CT-scan revealed the presence of a subdural abscess. After
      consulting the neurosurgeon, the patient was treated conservatively with
      antimicrobial drugs. Three weeks later he returned home without any symptoms.
      Since then, he is visiting regularly our clinic and no problems occurred during
      follow-up.

PMID- 19178715
TI  - A case study for teaching information literacy skills.
AB  - BACKGROUND: The Internet has changed contemporary workplace skills, resulting in
      a need for proficiency with specific digital, online and web-based technologies
      within the fields of medicine, dentistry and public health. Although younger
      students, generally under 30 years of age, may appear inherently comfortable with
      the use of technology-intensive environments and digital or online search
      methods, competence in information literacy among these students may be lacking.
      METHODS: This project involved the design and assessment of a research-based
      assignment to help first-year, graduate-level health science students to develop
      and integrate information literacy skills with clinical relevance. RESULTS: One
      cohort of dental students (n = 78) was evaluated for this project and the results
      demonstrate that although all students were able to provide the correct response
      from the content-specific, or technology-independent, portion of the assignment,
      more than half (54%) were unable to demonstrate competence with a web-based,
      technology-dependent section of this assignment. No correlation was found between
      any demographic variable measured (gender, age, or race). CONCLUSION: More
      evidence is emerging that demonstrates the need for developing curricula that
      integrates new knowledge and current evidence-based practices and technologies,
      traditionally isolated from graduate and health-care curricula, that can enhance
      biomedical and clinical training for students. This study provides evidence,
      critical for the evaluation of new practices, which can promote and facilitate
      the integration of information literacy into the curriculum.

PMID- 19178716
TI  - Forecasting daily attendances at an emergency department to aid resource
      planning.
AB  - BACKGROUND: Accurate forecasting of emergency department (ED) attendances can be
      a valuable tool for micro and macro level planning. METHODS: Data for analysis
      was the counts of daily patient attendances at the ED of an acute care regional
      general hospital from July 2005 to Mar 2008. Patients were stratified into three
      acuity categories; i.e. P1, P2 and P3, with P1 being the most acute and P3 being
      the least acute. The autoregressive integrated moving average (ARIMA) method was
      separately applied to each of the three acuity categories and total patient
      attendances. Independent variables included in the model were public holiday (yes
      or no), ambient air quality measured by pollution standard index (PSI), daily
      ambient average temperature and daily relative humidity. The seasonal components
      of weekly and yearly periodicities in the time series of daily attendances were
      also studied. Univariate analysis by t-tests and multivariate time series
      analysis were carried out in SPSS version 15. RESULTS: By time series analyses,
      P1 attendances did not show any weekly or yearly periodicity and was only
      predicted by ambient air quality of PSI > 50. P2 and total attendances showed
      weekly periodicities, and were also significantly predicted by public holiday. P3
      attendances were significantly correlated with day of the week, month of the
      year, public holiday, and ambient air quality of PSI > 50.After applying the
      developed models to validate the forecast, the MAPE of prediction by the models
      were 16.8%, 6.7%, 8.6% and 4.8% for P1, P2, P3 and total attendances,
      respectively. The models were able to account for most of the significant
      autocorrelations present in the data. CONCLUSION: Time series analysis has been
      shown to provide a useful, readily available tool for predicting emergency
      department workload that can be used to plan staff roster and resource planning.

PMID- 19178718
TI  - Chronic digital infection presenting with gross enlargement of the toes: two case
      reports and review of the literature.
AB  - There are many conditions ranging from the benign to the malignant, which can
      present with enlargement of one or more digits. An understanding of the
      differential diagnosis is important such that the potentially serious aetiologies
      are not missed and patients can therefore be treated appropriately. We present
      two patients, a male and a female aged 58 and 49 respectively, who presented to
      orthopaedic surgeons with gross enlargement of the toes. There were significant
      delays to presentation in both cases. Histological and microbiological analysis
      revealed that chronic, untreated infection was the most likely cause in both
      cases. Both patients were successfully treated by amputation of the offending
      digits. Congenital, infective, inflammatory and neoplastic conditions may all
      cause enlargement of a digit. The cause should be thoroughly sought prior to
      deciding upon management. Amputation can be successful, enables definitive tissue
      diagnosis and allows quick return to normal activities. The correct level must be
      identified pre-operatively.

PMID- 19178717
TI  - The salivary gland transcriptome of the neotropical malaria vector Anopheles
      darlingi reveals accelerated evolution of genes relevant to hematophagy.
AB  - BACKGROUND: Mosquito saliva, consisting of a mixture of dozens of proteins
      affecting vertebrate hemostasis and having sugar digestive and antimicrobial
      properties, helps both blood and sugar meal feeding. Culicine and anopheline
      mosquitoes diverged ~150 MYA, and within the anophelines, the New World species
      diverged from those of the Old World ~95 MYA. While the sialotranscriptome (from
      the Greek sialo, saliva) of several species of the Cellia subgenus of Anopheles
      has been described thoroughly, no detailed analysis of any New World anopheline
      has been done to date. Here we present and analyze data from a comprehensive
      salivary gland (SG) transcriptome of the neotropical malaria vector Anopheles
      darlingi (subgenus Nyssorhynchus). RESULTS: A total of 2,371 clones randomly
      selected from an adult female An. darlingi SG cDNA library were sequenced and
      used to assemble a database that yielded 966 clusters of related sequences, 739
      of which were singletons. Primer extension experiments were performed in selected
      clones to further extend sequence coverage, allowing for the identification of
      183 protein sequences, 114 of which code for putative secreted proteins.
      CONCLUSION: Comparative analysis of sialotranscriptomes of An. darlingi and An.
      gambiae reveals significant divergence of salivary proteins. On average, salivary
      proteins are only 53% identical, while housekeeping proteins are 86% identical
      between the two species. Furthermore, An. darlingi proteins were found that match
      culicine but not anopheline proteins, indicating loss or rapid evolution of these
      proteins in the old world Cellia subgenus. On the other hand, several well
      represented salivary protein families in old world anophelines are not expressed
      in An. darlingi.

PMID- 19178720
TI  - Cryptococcal meningitis presenting with recurrent syncope in a patient with
      chronic lymphoid leukemia: a case report.
AB  - The clinical presentations of cryptococcal meningitis in HIV-negative patients
      may be different from that infected with HIV. We report a case of 75-year old
      male with chronic lymphoid leukemia presenting with recurrent syncope, bi-frontal
      headache and diplopia. This case discusses the atypical presentations of
      cryptococcal meningitis in HIV-negative patients and its importance of early
      diagnosis.

PMID- 19178719
TI  - Disclosure of cancer diagnosis and quality of life in cancer patients: should it
      be the same everywhere?
AB  - BACKGROUND: Evidence suggests that truth telling and honest disclosure of cancer
      diagnosis could lead to improved outcomes in cancer patients. To examine such
      findings in Iran, this trial aimed to study the various dimensions of quality of
      life in patients with gastrointestinal cancer and to compare these variables
      among those who knew their diagnosis and those who did not. METHODS: A
      consecutive sample of patients with gastrointestinal cancer being treated in
      Cancer Institute in Tehran, Iran was prospectively evaluated. A psychologist
      interviewed patients using the Iranian version of the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).
      Patients were categorized into two groups: those who knew their diagnosis and
      those who did not. Independent sample t-test was used for group comparisons.
      RESULTS: In all 142 patients were interviewed. A significant proportion (52%) of
      patients did not know their cancer diagnosis and 48% of patients were aware that
      they had cancer. They were quite similar in most characteristics. The comparison
      of quality of life between two groups indicated that those knew their diagnosis
      showed a significant lower degree of physical (P = 0.001), emotional (P = 0.01)
      and social functioning (P < 0.001), whereas the global quality of life and other
      functional scales including role functioning and cognitive functioning did not
      show significant result. There were no statistically significant differences
      between symptoms scores between two groups, except for fatigue suggesting a
      higher score in patients who knew their diagnosis (P = 0.01). The financial
      difficulties were also significantly higher in patients who knew their cancer
      diagnosis (P = 0.005). Performing analysis of variance while controlling for age,
      educational status, cancer site, and knowledge of cancer diagnosis, the results
      showed that the knowledge of cancer diagnosis independently still contributed to
      the significant differences observed between two groups. CONCLUSION: Contrary to
      expectation the findings indicated that patients who did not know their cancer
      diagnosis had a better physical, social and emotional quality of life. It seems
      that due to cultural differences between countries cancer disclosure guidelines
      perhaps should be differing.

PMID- 19178721
TI  - Metabolic effects of low glycaemic index diets.
AB  - The persistence of an epidemic of obesity and type 2 diabetes suggests that new
      nutritional strategies are needed if the epidemic is to be overcome. A promising
      nutritional approach suggested by this thematic review is metabolic effect of low
      glycaemic-index diet. The currently available scientific literature shows that
      low glycaemic-index diets acutely induce a number of favorable effects, such as a
      rapid weight loss, decrease of fasting glucose and insulin levels, reduction of
      circulating triglyceride levels and improvement of blood pressure. The long-term
      effect of the combination of these changes is at present not known. Based on
      associations between these metabolic parameters and risk of cardiovascular
      disease, further controlled studies on low-GI diet and metabolic disease are
      needed.

PMID- 19178722
TI  - High-resolution mapping of heterochromatin redistribution in a Drosophila
      position-effect variegation model.
AB  - BACKGROUND: Position-effect variegation (PEV) is the stochastic transcriptional
      silencing of a gene positioned adjacent to heterochromatin. white-mottled X
      chromosomal inversions in Drosophila are classic PEV models that show variegation
      of the eye color gene white due to its relocation next to pericentric
      heterochromatin. It has been suggested that in these models the spreading of
      heterochromatin across the rearrangement breakpoint causes the silencing of
      white. However, the extent of this spreading and the precise pattern of
      heterochromatin redistribution have remained unclear. To obtain insight into the
      mechanism of PEV, we constructed high-resolution binding maps of Heterochromatin
      Protein 1 (HP1) on white-mottled chromosomes. RESULTS: We find that HP1 invades
      euchromatin across the inversion breakpoints over approximately 175 kb and
      approximately 30 kb, causing de novo association of HP1 with 20 genes. However,
      HP1 binding levels in these regions show substantial local variation, and white
      is the most strongly bound gene. Remarkably, white is also the only gene that is
      detectably repressed by heterochromatin. Furthermore, we find that HP1 binding to
      the invaded region is particularly sensitive to the dosage of the histone
      methyltransferase Su(var)3-9, indicating that the de novo formed heterochromatin
      is less stable than naturally occurring constitutive heterochromatin. CONCLUSION:
      Our molecular maps demonstrate that heterochromatin can invade a normally
      euchromatic region, yet the strength of HP1 binding and effects on gene
      expression are highly dependent on local context. Our data suggest that the white
      gene has an unusual intrinsic affinity for heterochromatin, which may cause this
      gene to be more sensitive to PEV than most other genes.

PMID- 19178723
TI  - DFP: a Bioconductor package for fuzzy profile identification and gene reduction
      of microarray data.
AB  - BACKGROUND: Expression profiling assays done by using DNA microarray technology
      generate enormous data sets that are not amenable to simple analysis. The
      greatest challenge in maximizing the use of this huge amount of data is to
      develop algorithms to interpret and interconnect results from different genes
      under different conditions. In this context, fuzzy logic can provide a systematic
      and unbiased way to both (i) find biologically significant insights relating to
      meaningful genes, thereby removing the need for expert knowledge in preliminary
      steps of microarray data analyses and (ii) reduce the cost and complexity of
      later applied machine learning techniques being able to achieve interpretable
      models. RESULTS: DFP is a new Bioconductor R package that implements a method for
      discretizing and selecting differentially expressed genes based on the
      application of fuzzy logic. DFP takes advantage of fuzzy membership functions to
      assign linguistic labels to gene expression levels. The technique builds a
      reduced set of relevant genes (FP, Fuzzy Pattern) able to summarize and represent
      each underlying class (pathology). A last step constructs a biased set of genes
      (DFP, Discriminant Fuzzy Pattern) by intersecting existing fuzzy patterns in
      order to detect discriminative elements. In addition, the software provides new
      functions and visualisation tools that summarize achieved results and aid in the
      interpretation of differentially expressed genes from multiple microarray
      experiments. CONCLUSION: DFP integrates with other packages of the Bioconductor
      project, uses common data structures and is accompanied by ample documentation.
      It has the advantage that its parameters are highly configurable, facilitating
      the discovery of biologically relevant connections between sets of genes
      belonging to different pathologies. This information makes it possible to
      automatically filter irrelevant genes thereby reducing the large volume of data
      supplied by microarray experiments. Based on these contributions GENECBR, a
      successful tool for cancer diagnosis using microarray datasets, has recently been
      released.

PMID- 19178724
TI  - Angiosarcoma of the nasal cavity: a case report.
AB  - Angiosarcomas are malignant neoplasias of rapid growth that develop from
      endothelial cells. They represent 2% of all sarcomas and only 1-4% are located in
      the aerodigestive tract. Since 1977, only 16 cases have been reported.We present
      a 33-year-old male with spontaneous epistaxis that was refractory to
      cauterization. During physical examination, a smooth purplish tumor of 1.5 cm x
      1.5 cm was identified. A CT scan showed a nonenhanced tumor in the left nostril
      on the uncinate process. A biopsy revealed an intermediate-grade angiosarcoma.
      Surgical removal followed by radiation therapy was performed with good result.
      Aerodigestive angiosarcomas have a better prognosis than angiosarcomas of other
      locations due to better cell differentiation and the presence of early symptoms.
      Recurrence can occur because of tumor tissue left during resection. Our patient
      continues tumor free after three years.

PMID- 19178725
TI  - A rare cause of recurrent gastrointestinal bleeding: mesenteric hemangioma.
AB  - Lower gastrointestinal hemorrhage accounts for approximately 20% of
      gastrointestinal hemorrhage. The most common causes of lower gastrointestinal
      hemorrhage in adults are diverticular disease, inflammatory bowel disease, benign
      anorectal diseases, intestinal neoplasias, coagulopathies and arterio-venous
      malformations. Hemangiomas of gastrointestinal tract are rare. Mesenteric
      hemangiomas are also extremely rare.We present a 25-year-old female who was
      admitted to the emergency room with recurrent lower gastrointestinal bleeding. An
      intraluminal bleeding mass inside the small intestinal segment was detected
      during explorative laparotomy as the cause of the recurrent lower
      gastrointestinal bleeding. After partial resection of small bowel segment, the
      histopathologic examination revealed a cavernous hemagioma of mesenteric
      origin.Although rare, gastrointestinal hemangioma should be thought in
      differential diagnosis as a cause of recurrent lower gastrointestinal bleeding.

PMID- 19178726
TI  - Analysing the origin of long-range interactions in proteins using lattice models.
AB  - BACKGROUND: Long-range communication is very common in proteins but the physical
      basis of this phenomenon remains unclear. In order to gain insight into this
      problem, we decided to explore whether long-range interactions exist in lattice
      models of proteins. Lattice models of proteins have proven to capture some of the
      basic properties of real proteins and, thus, can be used for elucidating general
      principles of protein stability and folding. RESULTS: Using a computational
      version of double-mutant cycle analysis, we show that long-range interactions
      emerge in lattice models even though they are not an input feature of them. The
      coupling energy of both short- and long-range pairwise interactions is found to
      become more positive (destabilizing) in a linear fashion with increasing 'contact
      frequency', an entropic term that corresponds to the fraction of states in the
      conformational ensemble of the sequence in which the pair of residues is in
      contact. A mathematical derivation of the linear dependence of the coupling
      energy on 'contact-frequency' is provided. CONCLUSION: Our work shows how
      'contact-frequency' should be taken into account in attempts to stabilize
      proteins by introducing (or stabilizing) contacts in the native state and/or
      through 'negative design' of non-native contacts.

PMID- 19178727
TI  - Malaria and water resource development: the case of Gilgel-Gibe hydroelectric dam
      in Ethiopia.
AB  - BACKGROUND: Ethiopia plans to increase its electricity power supply by five-fold
      over the next five years to fulfill the needs of its people and support the
      economic growth based on large hydropower dams. Building large dams for
      hydropower generation may increase the transmission of malaria since they
      transform ecosystems and create new vector breeding habitats. The aim of this
      study was to assess the effects of Gilgel-Gibe hydroelectric dam in Ethiopia on
      malaria transmission and changing levels of prevalence in children. METHODS: A
      cross-sectional, community-based study was carried out between October and
      December 2005 in Jimma Zone, south-western Ethiopia, among children under 10
      years of age living in three 'at-risk' villages (within 3 km from dam) and three
      'control' villages (5 to 8 km from dam). The man-made Gilgel-Gibe dam is
      operating since 2004. Households with children less than 10 years of age were
      selected and children from the selected households were sampled from all the six
      villages. This included 1,081 children from 'at-risk' villages and 774 children
      from 'control' villages. Blood samples collected from children using finger prick
      were examined microscopically to determine malaria prevalence, density of
      parasitaemia and identify malarial parasite species. RESULTS: Overall 1,855
      children (905 girls and 950 boys) were surveyed. A total of 194 (10.5%) children
      were positive for malaria, of which, 117 (60.3%) for Plasmodium vivax, 76 (39.2%)
      for Plasmodium falciparum and one (0.5%) for both P. vivax and P. falciparum. A
      multivariate design-based analysis indicated that, while controlling for age, sex
      and time of data collection, children who resided in 'at-risk' villages close to
      the dam were more likely to have P. vivax infection than children who resided
      farther away (odds ratio (OR) = 1.63, 95% CI = 1.15, 2.32) and showed a higher OR
      to have P. falciparum infection than children who resided in 'control' villages,
      but this was not significant (OR = 2.40, 95% CI = 0.84, 6.88). A classification
      tree revealed insights in the importance of the dam as a risk factor for malaria.
      Assuming that the relationship between the dam and malaria is causal, 43% of the
      malaria occurring in children was due to living in close proximity to the dam.
      CONCLUSION: This study indicates that children living in close proximity to a man
      made reservoir in Ethiopia are at higher risk of malaria compared to those living
      farther away. It is recommended that sound prevention and control programme be
      designed and implemented around the reservoir to reduce the prevalence of
      malaria. In this respect, in localities near large dams, health impact assessment
      through periodic survey of potential vectors and periodic medical screening is
      warranted. Moreover, strategies to mitigate predicted negative health outcomes
      should be integral parts in the preparation, construction and operational phases
      of future water resource development and management projects.

PMID- 19178729
TI  - Ventricular noncompaction in a female patient with nephropathic cystinosis: a
      case report.
AB  - INTRODUCTION: We report an unusual and interesting case of a 24-year-old woman
      with nephropathic cystinosis in association with concomitant isolated
      noncompaction of the left ventricle. Left ventricular noncompaction usually
      presents with reduced exercise tolerance as a consequence of ventricular
      dysfunction, the result of embolus or with palpitations and syncope due to
      arrhythmia. There is no specific treatment directed at isolated noncompaction.
      Treatment is focused on the cause of presentation, with medication aimed at
      improving ventricular dysfunction, as well as treating and preventing thrombosis
      and arrhythmia. CASE PRESENTATION: Our patient presented with an episode of
      decompensated heart failure. Trans-thoracic echocardiography demonstrated
      excessive trabeculation with inter-trabecular recesses in the left ventricle
      typical of noncompaction of the left ventricle. The patient's admission was
      complicated by a cardiac arrest precipitated by ventricular tachycardia for which
      she subsequently underwent implantation of an automatic implantable cardioverter
      defibrillator. CONCLUSION: This is, as far as we know, the first case report of
      the co-existence of nephropathic cystinosis and isolated noncompaction of the
      left ventricle. It highlights the importance of being vigilant to the diagnosis
      of left ventricular noncompaction.

PMID- 19178728
TI  - Identifying diabetic patients with cardiac autonomic neuropathy by heart rate
      complexity analysis.
AB  - BACKGROUND: Cardiac autonomic neuropathy (CAN) in diabetes has been called a
      "silent killer", because so few patients realize that they suffer from it, and
      yet its effect can be lethal. Early sub clinical detection of CAN and
      intervention are of prime importance for risk stratification in preventing sudden
      death due to silent myocardial infarction. This study presents the usefulness of
      heart rate variability (HRV) and complexity analyses from short term ECG
      recordings as a screening tool for CAN. METHODS: A total of 17 sets of ECG
      recordings during supine rest were acquired from diabetic subjects with CAN
      (CAN+) and without CAN (CAN-) and analyzed. Poincare plot indexes as well as
      traditional time and frequency, and the sample entropy (SampEn) measure were used
      for analyzing variability (short and long term) and complexity of HRV
      respectively. RESULTS: Reduced (p > 0.05)_Poincare plot patterns and lower (p <
      0.05) SampEn values were found in CAN+ group, which could be a practical
      diagnostic and prognostic marker. Classification Trees methodology generated a
      simple decision tree for CAN+ prediction including SampEn and Poincare plot
      indexes with a sensitivity reaching 100% and a specificity of 75% (percentage of
      agreement 88.24%). CONCLUSION: Our results demonstrate the potential utility of
      SampEn (a complexity based estimator) of HRV in identifying asymptomatic CAN.

PMID- 19178730
TI  - Facial skin metastasis due to small-cell lung cancer: a case report.
AB  - INTRODUCTION: Cutaneous metastases in the facial region occur in less than 0.5%
      of patients with metastatic cancer. They are an important finding and are not
      often the first sign leading to diagnosis. CASE PRESENTATION: We describe the
      case of a 64-year-old male patient who presented with dyspnea, pleuritic pain,
      loss of weight and a nodule on his left cheek. A chest X-ray revealed a left
      upper lobe mass with mediastinal lymphadenopathy. Excision biopsy of the facial
      nodule revealed small-cell lung carcinoma. Palliative chemo-radiotherapy was
      administered and the patient survived for 12 months. CONCLUSION: A high index of
      suspicion is necessary for the early detection of facial cutaneous metastases.
      Appropriate treatment may prolong patient survival.

PMID- 19178731
TI  - Femoral nerve compression secondary to a ganglion cyst arising from a hip joint:
      a case report and review of the literature.
AB  - INTRODUCTION: Femoral nerve compression due to a cystic lesion around the hip
      joint is rare and only a few cases have been described in the literature. Among
      these, true ganglion cysts are even more rare. CASE PRESENTATION: We report the
      case of a 57-year-old woman with femoral nerve compression caused by a true
      ganglion cyst of the hip joint. CONCLUSION: A high index of suspicion is required
      to predict a non-palpable cystic lesion around the hip joint as it may mimic
      different disorders and should be kept in mind in the differential diagnosis of
      unusual groin pain, radicular pain and peripheral vascular disorders.

PMID- 19178732
TI  - Low Spigelian hernia in a 6-year-old boy presenting as an incarcerated inguinal
      hernia: a case report.
AB  - INTRODUCTION: Lower Spigelian hernia is a very rare entity. The clinical findings
      are similar to those of inguinal hernias and in many cases may be misdiagnosed.
      In the literature, only a few references to this entity have been reported in
      children. To the best of our knowledge, this is the first case report of a lower
      Spigelian hernia in a child who presented with an acute painful scrotum. CASE
      PRESENTATION: We discuss the case of a 6-year-old Greek boy who presented to our
      emergency department complaining of severe pain in the left inguinal area and
      scrotum. The acute painful swelling started suddenly, without any obvious cause.
      The initial diagnosis was incarcerated inguinal hernia which was reduced with
      difficulty. Five days later, the patient still experienced mild pain during
      palpation and he was operated on. During the operation, a large lower Spigelian
      hernia was revealed and reconstructed. CONCLUSION: Although Spigelian hernias are
      rare in children and difficult to diagnose, physicians should be aware of them
      and include them in the differential diagnosis.

PMID- 19178733
TI  - Interpretation of illness in cancer survivors is associated with health-related
      variables and adaptive coping styles.
AB  - BACKGROUND: A patient's interpretation of illness may have an influence on the
      choice of coping strategies and decision making. We intended to analyze the
      meaning German cancer survivors would attribute to their disease, and
      investigated intercorrelations between the respective interpretations, health
      related variables and adaptive coping strategies. METHODS: In an anonymous cross
      sectional survey, we analyzed the interpretations of disease (according to
      Lipowski's eight 'meaning of illness' categories) in 387 patients with cancer
      (81% breast cancer). To make statements about their conceptual relationships with
      health-related variables, we correlated the 8 items of the 'Interpretation of
      Illness' questionnaire (IIQ) with health-related quality of life,
      anxiety/depression, fatigue, life satisfaction, and adaptive coping strategies.
      RESULTS: Most cancer survivors regarded their disease as a challenge (52%),
      others as value (38%) or even an interruption of life (irreparable loss; 35%);
      weakness/failure (5%) and punishment (3%) were rated the lowest. The fatalistic
      negative interpretations 'interruption/loss' and 'enemy/threat' were inversely
      correlated with mental health-related quality of life and life satisfaction, and
      positively with an escape-avoidance strategy, depression and anxiety. In
      contrast, positive disease interpretations (i.e., 'challenge' and 'value')
      correlated only with adaptive coping strategies. Physical health correlated with
      none of the disease interpretations. CONCLUSION: Despite conceptual limitations,
      the 8-item schema could be regarded as a useful screening approach to identify
      patients at risk for reduced psychosocial functioning.

PMID- 19178734
TI  - Synchronously diagnosed eosinophilic granuloma and Hodgkin's disease in a 12-year
      old boy: a case report.
AB  - INTRODUCTION: Synchronous composite tumors are uncommon. Simultaneous, rather
      than metachronous or consecutive, occurrences of eosinophilic granuloma and
      Hodgkin's lymphoma in children are very rare. This is the first report of this
      kind in the medical literature. CASE PRESENTATION: We report the case of a 12
      year-old Iranian boy with eosinophilic granuloma localized in his leg around the
      knee and Hodgkin's lymphoma in a cervical lymph node. The two tumours occurred
      synchronously before the patient had received any treatment. CONCLUSION: Several
      cases of an association between eosinophilic granuloma and lymphoproliferative
      disorder have been reported. Some of these cases involve Hodgkin's lymphoma and
      Langerhans cell histiocytosis occurring in the same patient. Genetic or
      environmental etiologies have been postulated for eosinophilic granulomas which
      occur following Hodgkin's lymphomas, but have as yet not been proven. To our
      knowledge, synchronous occurrence of these two malignant processes in a patient
      who has not received any prior treatment is rare in children.

PMID- 19178735
TI  - Sensorineural hearing loss in Lassa fever: two case reports.
AB  - INTRODUCTION: Lassa fever is an acute arena viral haemorrhagic fever with varied
      neurological sequelae. Sensorineural hearing loss is one of the rare
      complications which occur usually during the convalescent stage of the infection.
      CASE PRESENTATION: The cases of two female patients aged 19 and 43 years old,
      respectively, with clinical features suggestive of Lassa fever and confirmed by
      immunoserological/Lassa-virus-specific reverse transcriptase polymerase chain
      reaction are presented. Both patients developed severe sensorineural hearing loss
      at acute phases of the infections. CONCLUSION: Sensorineural hearing loss from
      Lassa fever infections can occur in both acute and convalescent stages and is
      probably induced by an immune response.

PMID- 19178736
TI  - Co-infection by Streptococcus anginosus and Mycobacterium tuberculosis: three
      case reports.
AB  - INTRODUCTION: Bacterial infections may appear as sequelae of remote tuberculous
      infections, especially thoracic infections. The simultaneous appearance of
      tuberculosis and bacterial infection is not common, and, to our knowledge, the
      association of infection by Streptococcus anginosus and Mycobacterium
      tuberculosis has not been reported previously in the literature. CASE
      PRESENTATION: We report three cases of dual infection with Streptococcus
      anginosus and Mycobacterium tuberculosis that were first diagnosed as pyogenic
      abscesses because of an isolation of Streptococcus anginosus. Despite a course of
      antibiotics and drainage, the outcome of this initial treatment was unfavourable.
      A re-evaluation yielded a diagnosis of mixed infection with Streptococcus
      anginosus and Mycobacterium tuberculosis. CONCLUSION: In a geographical area with
      a high prevalence of tuberculous disease, the rare possibility of dual infection
      with Streptococcus anginosus and Mycobacterium tuberculosis should be considered.

PMID- 19178737
TI  - A rare case of term viable secondary abdominal pregnancy following rupture of a
      rudimentary horn: a case report.
AB  - INTRODUCTION: Abdominal pregnancy is a rare event, but one that represents a
      grave risk to the health of the pregnant woman. An abdominal pregnancy is defined
      as an ectopic pregnancy that implants in the peritoneal cavity. Early abdominal
      pregnancy is self-limited by hemorrhage from trophoblastic invasion with complete
      abortion of the gestational sac that leaves a discrete crater. Advanced abdominal
      pregnancy is a rare event, with high fetal and maternal morbidity and mortality.
      CASE PRESENTATION: This is a case report of a 22-year-old primigravida with an
      abdominal pregnancy from a ruptured rudimentary horn. She was diagnosed as a case
      of term pregnancy with placenta previa with a transverse fetal lie and cervical
      fibroid and was prepared for an elective cesarean section. Intra-operatively, a
      live term female baby was extracted from the peritoneal cavity and it turned out
      to be an abdominal pregnancy from a ruptured rudimentary horn of a unicornuate
      uterus, which is a very rare condition. Mother and baby were in good condition
      after such a catastrophic event. CONCLUSION: This case illustrates a rare
      obstetric condition which can be a severe catastrophic condition leading to
      maternal mortality and morbidity. It is imperative for every obstetrician to have
      in mind the possibility of abdominal pregnancy, although rare, especially in
      pregnant patients with persistent abdominal pain and painful fetal movements.

PMID- 19178738
TI  - Primary osteosarcoma of the urinary bladder following cyclophosphamide therapy
      for systemic lupus erythematosus: a case report.
AB  - INTRODUCTION: The association of systemic lupus erythematosus with malignancies
      is an uncommon occurrence. We present the case of an osteosarcoma of the urinary
      bladder developing in a patient with a prolonged history of active systemic lupus
      erythematosus. This is a previously unreported association. Primary osteosarcoma
      is an extremely rare disease in the urinary bladder. CASE PRESENTATION: A 24-year
      old Caucasian woman with a 13-year history of systemic lupus erythematosus, who
      had been treated with high dose immunosuppressive agents, presented with pain and
      hematuria. A deeply invasive high-grade tumor was detected in the urinary bladder
      and the patient underwent radical surgery. A diagnosis of osteosarcoma was made
      based on the characteristic histology. CONCLUSION: Predisposing factors for
      primary sarcomas in the urinary bladder are mostly unknown; however, in our case,
      long-term administration of immunosuppressive agents, as well as long standing
      systemic lupus erythematosus, may both be of significance.

PMID- 19178739
TI  - Arthritis of the sternoclavicular joint masquerading as rupture of the cervical
      oesophagus: a case report.
AB  - INTRODUCTION: Sternoclavicular septic arthritis is a rare condition and accounts
      only for 1% of cases of septic arthritis in the general population. The most
      common risk factors are intravenous drug use, central-line infection, distant
      site infection, immunosuppression, trauma and diabetes mellitus. This is a report
      of an unusual case where this type of arthritis was masquerading as rupture of
      the cervical oesophagus. CASE PRESENTATION: A 63-year-old man presented
      complaining of right neck pain and dysphagia following a bout of violent
      coughing. Physical examination revealed cellulitis extending from the right
      sternoclidomastoid region to the anterior upper chest. Computed tomography showed
      inflammatory changes behind the right sternoclavicular joint with mediastinitis
      and ipsilateral pleural effusion. These findings raised the suspicion of
      spontaneous rupture of the cervical oesophagus. Management involved jejunal
      feeding along with broad-spectrum antibiotics. The inflammation, however,
      relapsed after discontinuation of the antibiotics and this time, computed
      tomography pointed to a diagnosis of arthritis of the sternoclavicular joint. The
      patient responded completely to a 6-week course of oral penicillin,
      flucloxacillin and metronidazole. CONCLUSION: Sternoclavicular arthritis is a
      rare condition that has been associated with a variety of predisposing factors.
      It may, however, occur in otherwise completely healthy individuals and should be
      included in the differential diagnosis of other inflammatory conditions of the
      neck and upper chest.

PMID- 19178740
TI  - On reliable discovery of molecular signatures.
AB  - BACKGROUND: Molecular signatures are sets of genes, proteins, genetic variants or
      other variables that can be used as markers for a particular phenotype. Reliable
      signature discovery methods could yield valuable insight into cell biology and
      mechanisms of human disease. However, it is currently not clear how to control
      error rates such as the false discovery rate (FDR) in signature discovery.
      Moreover, signatures for cancer gene expression have been shown to be unstable,
      that is, difficult to replicate in independent studies, casting doubts on their
      reliability. RESULTS: We demonstrate that with modern prediction methods,
      signatures that yield accurate predictions may still have a high FDR. Further, we
      show that even signatures with low FDR may fail to replicate in independent
      studies due to limited statistical power. Thus, neither stability nor predictive
      accuracy are relevant when FDR control is the primary goal. We therefore develop
      a general statistical hypothesis testing framework that for the first time
      provides FDR control for signature discovery. Our method is demonstrated to be
      correct in simulation studies. When applied to five cancer data sets, the method
      was able to discover molecular signatures with 5% FDR in three cases, while two
      data sets yielded no significant findings. CONCLUSION: Our approach enables
      reliable discovery of molecular signatures from genome-wide data with current
      sample sizes. The statistical framework developed herein is potentially
      applicable to a wide range of prediction problems in bioinformatics.

PMID- 19178741
TI  - Private doctors' practices, knowledge, and attitude to reporting of communicable
      diseases: a national survey in Taiwan.
AB  - BACKGROUND: Epidemiological surveillance of infectious diseases through the
      mandatory-reporting system is crucial in the planning and evaluation of disease
      control and prevention program. This study investigated the reporting behavior,
      knowledge, and attitude to reporting communicable disease in private doctors in
      Taiwan. The differences between the reporting and non-reporting doctors were also
      explored. METHODS: A total of 1250 clinics were randomly sampled nationwide by a
      2-stage process. Data were collected from 1093 private doctors (87.4% response
      rate) using a self-administered structured questionnaire. Four hundred and six
      (37.2%) doctors reported having diagnosed reportable communicable diseases. Among
      them, 340 (83.5%) have the experiences of reporting. RESULTS: The most common
      reasons for not reporting were "do not want to violate the patient's privacy",
      "reporting procedure is troublesome", and "not sure whether the diagnosed disease
      is reportable". Significantly higher proportions of the non-reporting doctors
      considered the reporting system inconvenient or were not familiar with the
      system. The highest percentage (65.2%) of the non-reporting doctors considered
      that a simplified reporting procedure, among all measures, would increase their
      willingness to report. In addition, a significantly higher proportion of the non
      reporting doctors would increase their willingness to report if there has been a
      good reward for reporting or a penalty for not reporting. CONCLUSION: The most
      effective way to improve reporting rate may be to modify doctor's attitude to
      disease reporting. The development of a convenient and widely-accepted reporting
      system and the establishment of a reward/penalty system may be essential in
      improving disease reporting compliance in private doctors.

PMID- 19178742
TI  - Linkage of cDNA expression profiles of mesencephalic dopaminergic neurons to a
      genome-wide in situ hybridization database.
AB  - Midbrain dopaminergic neurons are involved in control of emotion, motivation and
      motor behavior. The loss of one of the subpopulations, substantia nigra pars
      compacta, is the pathological hallmark of one of the most prominent neurological
      disorders, Parkinson's disease. Several groups have looked at the molecular
      identity of midbrain dopaminergic neurons and have suggested the gene expression
      profile of these neurons. Here, after determining the efficiency of each screen,
      we provide a linked database of the genes, expressed in this neuronal population,
      by combining and comparing the results of six previous studies and verification
      of expression of each gene in dopaminergic neurons, using the collection of in
      situ hybridization in the Allen Brain Atlas.

PMID- 19178743
TI  - Protein domain organisation: adding order.
AB  - BACKGROUND: Domains are the building blocks of proteins. During evolution, they
      have been duplicated, fused and recombined, to produce proteins with novel
      structures and functions. Structural and genome-scale studies have shown that
      pairs or groups of domains observed together in a protein are almost always found
      in only one N to C terminal order and are the result of a single recombination
      event that has been propagated by duplication of the multi-domain unit. Previous
      studies of domain organisation have used graph theory to represent the co
      occurrence of domains within proteins. We build on this approach by adding
      directionality to the graphs and connecting nodes based on their relative order
      in the protein. Most of the time, the linear order of domains is conserved.
      However, using the directed graph representation we have identified non-linear
      features of domain organization that are over-represented in genomes. Recognising
      these patterns and unravelling how they have arisen may allow us to understand
      the functional relationships between domains and understand how the protein
      repertoire has evolved. RESULTS: We identify groups of domains that are not
      linearly conserved, but instead have been shuffled during evolution so that they
      occur in multiple different orders. We consider 192 genomes across all three
      kingdoms of life and use domain and protein annotation to understand their
      functional significance. To identify these features and assess their statistical
      significance, we represent the linear order of domains in proteins as a directed
      graph and apply graph theoretical methods. We describe two higher-order patterns
      of domain organisation: clusters and bi-directionally associated domain pairs and
      explore their functional importance and phylogenetic conservation. CONCLUSION:
      Taking into account the order of domains, we have derived a novel picture of
      global protein organization. We found that all genomes have a higher than
      expected degree of clustering and more domain pairs in forward and reverse
      orientation in different proteins relative to random graphs with identical degree
      distributions. While these features were statistically over-represented, they are
      still fairly rare. Looking in detail at the proteins involved, we found strong
      functional relationships within each cluster. In addition, the domains tended to
      be involved in protein-protein interaction and are able to function as
      independent structural units. A particularly striking example was the human Jak
      STAT signalling pathway which makes use of a set of domains in a range of orders
      and orientations to provide nuanced signaling functionality. This illustrated the
      importance of functional and structural constraints (or lack thereof) on domain
      organisation.

PMID- 19178744
TI  - Health-related quality of life for pediatric emergency department febrile
      illnesses: an evaluation of the Pediatric Quality of Life Inventory 4.0 Generic
      Core Scales.
AB  - OBJECTIVE: We sought to assess the validity and short-term responsiveness of the
      Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) for febrile
      illnesses evaluated in the pediatric emergency department (ED). DESIGN:
      Prospective cohort study of children 2-18 years discharged after ED evaluation
      for fever (>or= 38 degrees C). Self-administered, parent-report of health-related
      quality of life (HRQOL) was assessed using the PedsQL Acute Version, a validated
      HRQOL instrument. HRQOL was measured on ED presentation and at 7-10 day follow
      up. At follow-up, duration of fever, child functional impairment, missed
      daycare/school, and disrupted family unit functioning, were assessed. RESULTS: Of
      160 subjects enrolled, 97 (61%) completed the study; mean follow-up was 8.7 days.
      Mean total HRQOL score on ED presentation was 76.4; mean follow-up score was
      86.3. Compared to subjects that returned to baseline, statistically significant
      differences in HRQOL were noted for those with prolonged fever, child functional
      impairment, and relapse. Significant correlation was observed between HRQOL at
      follow-up and days of daycare/school missed (r = -0.35, p = .003) and days of
      family disruption (r = -0.43, p < .001). Mean change in HRQOL within subjects,
      from ED visit to follow-up, was +9.8 (95% CI: 5.6-14.6). Effect size was 0.53,
      indicating moderate responsiveness. CONCLUSION: The PedsQL appears to be a valid
      and responsive indicator of HRQOL for short-term febrile illnesses evaluated in
      the ED.

PMID- 19178745
TI  - Nutrient intakes related to osteoporotic fractures in men and women--the
      Brazilian Osteoporosis Study (BRAZOS).
AB  - BACKGROUND: Adequate nutrition plays an important role in bone mass accrual and
      maintenance and has been demonstrated as a significant tool for the prevention of
      fractures in individuals with osteoporosis. OBJECTIVE: The aim of the present
      study was to evaluate bone health-related nutrients intake and its association
      with osteoporotic fractures in a representative sample of 2344 individuals aged
      40 years or older in Brazil. METHODS: In a transversal population-based study, a
      total of 2420 individuals over 40 years old were evaluated from March to April
      2006. Participants were men and women from all socio-economic classes and
      education levels living around the Brazilian territory Individuals responded a
      questionnaire including self reported fractures as well a 24-hour food recall.
      Nutrient intakes were evaluated by Nutrition Data System for Research software
      (NDSR, University of Minnesota, 2007). Low trauma fracture was defined as that
      resulting of a fall from standing height or less. Nutrient intakes adequacies
      were performed by using the DRI's proposed values. Statistical analysis comprises
      Oneway ANCOVA adjusted by age and use of nutritional supplements and multiple
      logistic regression. SAS software was used for statistical analysis. RESULTS:
      Fractures was reported by 13% of men and 15% of women. Women with fractures
      presented significantly higher calcium, phosphorus and magnesium intakes.
      However, in all regions and socio-economical levels mean intakes of bone related
      nutrients were below the recommended levels. It was demonstrated that for every
      100 mg/phosphorus increase the risk of fractures by 9% (OR 1.09; IC95% 1.05-1.13,
      p < 0.001). CONCLUSION: The results demonstrated inadequacies in bone related
      nutrients in our population as well that an increase in phosphorus intake is
      related to bone fractures.

PMID- 19178746
TI  - Development and evaluation of a Chinese-language newborn feeding hotline: a
      prospective cohort study.
AB  - BACKGROUND: Preference for formula versus breast feeding among women of Chinese
      descent remains a concern in North America. The goal of this study was to develop
      an intervention targeting Chinese immigrant mothers to increase their rates of
      exclusive breastfeeding. METHODS: We convened a focus group of immigrant women of
      Chinese descent in Vancouver, British Columbia to explore preferences for method
      of infant feeding. We subsequently surveyed 250 women of Chinese descent to
      validate focus group findings. Using a participatory approach, our focus group
      participants reviewed survey findings and developed a priority list for
      attributes of a community-based intervention to support exclusive breastfeeding
      in the Chinese community. The authors and focus group participants worked as a
      team to plan, implement and evaluate a Chinese language newborn feeding
      information telephone service staffed by registered nurses fluent in Chinese
      languages. RESULTS: Participants in the focus group reported a strong preference
      for formula feeding. Telephone survey results revealed that while pregnant
      Chinese women understood the benefits of breastfeeding, only 20.8% planned to
      breastfeed exclusively. Only 15.6% were breastfeeding exclusively at two months
      postpartum. After implementation of the feeding hotline, 20% of new Chinese
      mothers in Vancouver indicated that they had used the hotline. Among these women,
      the rate of exclusive breastfeeding was 44.1%; OR 3.02, (95% CI 1.78-5.09)
      compared to women in our survey. CONCLUSION: Initiation of a language-specific
      newborn feeding telephone hotline reached a previously underserved population and
      may have contributed to improved rates of exclusive breastfeeding.

PMID- 19178747
TI  - Intradialytic versus home-based exercise training in hemodialysis patients: a
      randomised controlled trial.
AB  - BACKGROUND: Exercise training in hemodialysis patients improves fitness, physical
      function, quality of life and markers of cardiovascular disease such as arterial
      stiffness. The majority of trials investigating this area have used supervised
      exercise training during dialysis (intradialytic), which may not be feasible for
      some renal units. The aim of this trial is to compare the effects of supervised
      intradialytic with unsupervised home-based exercise training on physical function
      and arterial stiffness. METHODS AND DESIGN: This is a randomised, controlled
      clinical trial. A total of 72 hemodialysis patients will be randomised to receive
      either six months of intradialytic exercise training, home-based exercise
      training or usual care. Intradialytic patients will undergo three training
      sessions per week on a cycle ergometer and home-based patients will be provided
      with a walking program to achieve the same weekly physical activity. Primary
      outcome measures are six-minute walk distance (6 MWD) and aortic pulse wave
      velocity (PWV). Secondary outcome measures include augmentation index, peripheral
      and central blood pressures, physical activity and self-reported health. Measures
      will be made at baseline, three and six months. DISCUSSION: The results of this
      study will help determine the efficacy of home-based exercise training in
      hemodialysis patients. This may assist in developing exercise guidelines specific
      for these patients. TRIAL REGISTRATION: ACTRN12608000247370

PMID- 19178748
TI  - A randomized prospective trial of the postoperative quality of life between
      laparoscopic uterine artery ligation and laparoscopy-assisted vaginal
      hysterectomy for the treatment of symptomatic uterine fibroids: clinical trial
      design.
AB  - BACKGROUND: Laparoscopy-assisted vaginal hysterectomy is one of the definite
      methods for the treatment of symptomatic uterine fibroids with lesser
      intraoperative bleeding and shorter hospitalization compared with abdominal
      hysterectomy. However, laparoscopy-assisted vaginal hysterectomy cannot preserve
      uterus and can show postoperative complications by the change of pelvic
      structure. Thus, laparoscopic uterine artery ligation has been introduced for
      relieving the symptoms caused by uterine fibroids in place of hysterectomy. The
      current study was designed to compare postoperative quality of life between
      laparoscopic uterine artery ligation and laparoscopy-assisted vaginal
      hysterectomy, and to evaluate the efficacy of laparoscopic uterine artery
      ligation which can treat symptomatic uterine fibroids with the preservation of
      uterus. METHODS AND DESIGN: Patients enrolled the current study are randomized to
      laparoscopic uterine artery ligation or laparoscopy-assisted vaginal
      hysterectomy. The primary outcome is to compare postoperative quality of life
      between laparoscopic uterine artery ligation and laparoscopy-assisted vaginal
      hysterectomy using the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire for Cancer patients version 3.0. Secondary outcomes
      are to evaluate the volume reduction of uterus, uterine fibroids and ovaries by
      the 2 treatments, to compare the improvement of subjective symptoms using 11
      point symptom score and postoperative clinical outcomes between laparoscopic
      uterine artery ligation and laparoscopy-assisted vaginal hysterectomy, and to
      investigate the improvement of postoperative vaginal bleeding by laparoscopic
      uterine artery ligation. DISCUSSION: Among treatment methods for symptomatic
      uterine fibroids with the preservation of uterus, laparoscopic uterine artery
      ligation is expected to have the efficacy like uterine artery embolization, which
      appeared to be safe for routine use with symptomatic relief. The current study
      fully recruited in June 2008 and the results will be available in June 2009. If
      there is no difference of postoperative QOL between laparoscopic uterine artery
      ligation and laparoscopy-assisted vaginal hysterectomy for the treatment of
      symptomatic uterine fibroids, the comparison of quality of life between
      laparoscopic uterine artery ligation and uterine artery embolization will be also
      needed as a surgical treatment for preserving uterus. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN76790866.

PMID- 19178749
TI  - Are youth mentoring programs good value-for-money? An evaluation of the Big
      Brothers Big Sisters Melbourne Program.
AB  - BACKGROUND: The Big Brothers Big Sisters (BBBS) program matches vulnerable young
      people with a trained, supervised adult volunteer as mentor. The young people are
      typically seriously disadvantaged, with multiple psychosocial problems. METHODS:
      Threshold analysis was undertaken to determine whether investment in the program
      was a worthwhile use of limited public funds. The potential cost savings were
      based on US estimates of life-time costs associated with high-risk youth who drop
      out-of-school and become adult criminals. The intervention was modelled for
      children aged 10-14 years residing in Melbourne in 2004. RESULTS: If the program
      serviced 2,208 of the most vulnerable young people, it would cost AUD 39.5 M.
      Assuming 50% were high-risk, the associated costs of their adult criminality
      would be AUD 3.3 billion. To break even, the program would need to avert high
      risk behaviours in only 1.3% (14/1,104) of participants. CONCLUSION: This
      indicative evaluation suggests that the BBBS program represents excellent 'value
      for money'.

PMID- 19178750
TI  - NIFTI: an evolutionary approach for finding number of clusters in microarray
      data.
AB  - BACKGROUND: Clustering techniques are routinely used in gene expression data
      analysis to organize the massive data. Clustering techniques arrange a large
      number of genes or assays into a few clusters while maximizing the intra-cluster
      similarity and inter-cluster separation. While clustering of genes facilitates
      learning the functions of un-characterized genes using their association with
      known genes, clustering of assays reveals the disease stages and subtypes. Many
      clustering algorithms require the user to specify the number of clusters a
      priori. A wrong specification of number of clusters generally leads to either
      failure to detect novel clusters (disease subtypes) or unnecessary splitting of
      natural clusters. RESULTS: We have developed a novel method to find the number of
      clusters in gene expression data. Our procedure evaluates different partitions
      (each with different number of clusters) from the clustering algorithm and finds
      the partition that best describes the data. In contrast to the existing methods
      that evaluate the partitions independently, our procedure considers the dynamic
      rearrangement of cluster members when a new cluster is added. Partition quality
      is measured based on a new index called Net InFormation Transfer Index (NIFTI)
      that measures the information change when an additional cluster is introduced.
      Information content of a partition increases when clusters do not intersect and
      decreases if they are not clearly separated. A partition with the highest Total
      Information Content (TIC) is selected as the optimal one. We illustrate our
      method using four publicly available microarray datasets. CONCLUSION: In all four
      case studies, the proposed method correctly identified the number of clusters and
      performs better than other well known methods. Our method also showed invariance
      to the clustering techniques.

PMID- 19178751
TI  - Development of a multi-locus sequence typing scheme for Laribacter hongkongensis,
      a novel bacterium associated with freshwater fish-borne gastroenteritis and
      traveler's diarrhea.
AB  - BACKGROUND: Laribacter hongkongensis is a newly discovered, facultative
      anaerobic, Gram-negative, motile, sea gull-shaped rod associated with freshwater
      fish borne gastroenteritis and traveler's diarrhea. A highly reproducible and
      discriminative typing system is essential for better understanding of the
      epidemiology of L. hongkongensis. In this study, a multilocus sequence typing
      (MLST) system was developed for L. hongkongensis. The system was used to
      characterize 146 L. hongkongensis isolates, including 39 from humans and 107 from
      fish. RESULTS: Fragments (362 to 504 bp) of seven housekeeping genes were
      amplified and sequenced. Among the 3068 bp of the seven loci, 332 polymorphic
      sites were observed. The median number of alleles at each locus was 34 [range 22
      (ilvC) to 45 (thiC)]. All seven genes showed very low d(n)/d(s) ratios of < 0.04,
      indicating that no strong positive selective pressure is present. A total of 97
      different sequence types (STs) were assigned to the 146 isolates, with 80 STs
      identified only once. The overall discriminatory power was 0.9861. eBURST grouped
      the isolates into 12 lineages, with six groups containing only isolates from fish
      and three groups only isolates from humans. Standardized index of association
      (I(S)(A)) measurement showed significant linkage disequilibrium in isolates from
      both humans and fish. The I(S)(A) for the isolates from humans and fish were
      0.270 and 0.636, indicating the isolates from fish were more clonal than the
      isolates from humans. Only one interconnected network (acnB) was detected in the
      split graphs. The P-value (P = 0) of sum of the squares of condensed fragments in
      Sawyer's test showed evidence of intragenic recombination in the rho, acnB and
      thiC loci, but the P-value (P = 1) of maximum condensed fragment in these gene
      loci did not show evidence of intragenic recombination. Congruence analysis
      showed that all the pairwise comparisons of the 7 MLST loci were incongruent,
      indicating that recombination played a substantial role in the evolution of L.
      hongkongensis. A website for L. hongkongensis MLST was set up and can be accessed
      at http://mlstdb.hku.hk:14206/MLST_index.html. CONCLUSION: A highly reproducible
      and discriminative MLST system was developed for L. hongkongensis.

PMID- 19178752
TI  - Successful renal re-transplantation in the presence of pre-existing anti-DQ5
      antibodies when there was zero mismatch at class I human leukocyte antigen A, B,
      & C: a case report.
AB  - INTRODUCTION: Hyperacute rejection may be prevented by avoiding the
      transplantation of kidneys into patients with pre-existing anti-donor Class I
      human leukocyte antigen antibodies. However, the role of anti-donor-Class II
      human leukocyte antigen-DQ antibodies is not established. The question is ever
      more relevant as more sensitive cross-matching techniques detect many additional
      antibodies during the final crossmatch. We now report successful renal
      transplantation of a patient who had pre-existing antibodies against his donor's
      human leukocyte antigen-DQ5. CASE PRESENTATION: Our patient, a Caucasian man, was
      34 years of age when he received his first deceased donor renal transplant. After
      8 years, his first transplant failed from chronic allograft dysfunction and an
      earlier bout of Banff 1A cellular rejection. The second deceased donor kidney
      transplant was initially allocated to the patient due to a 0 out of 6 mismatch.
      The B cell crossmatch was mildly positive, while the T Cell crossmatch was
      negative. Subsequent assays showed that the patient had preformed antibodies for
      human leukocyte antigen DQ5 against his second donor. Despite having preformed
      antibodies against the donor, the patient continues to have excellent allograft
      function two years after his second renal transplant. CONCLUSION: The presence of
      pre-existing antibodies against human leukocyte antigen DQ5 does not preclude
      transplantation. The relevance of having other antibodies against class II human
      leukocyte antigens prior to transplantation remains to be studied.

PMID- 19178753
TI  - The effects of DNA formulation and administration route on cancer therapeutic
      efficacy with xenogenic EGFR DNA vaccine in a lung cancer animal model.
AB  - BACKGROUND: Tyrosine kinase inhibitor gefitinib is effective against lung cancer
      cells carrying mutant epidermal growth factor receptor (EGFR); however, it is not
      effective against lung cancer carrying normal EGFR. The breaking of immune
      tolerance against self epidermal growth factor receptor with active immunization
      may be a useful approach for the treatment of EGFR-positive lung tumors.
      Xenogeneic EGFR gene was demonstrated to induce antigen-specific immune response
      against EGFR-expressing tumor with intramuscular administration. METHODS: In
      order to enhance the therapeutic effect of xenogeneic EGFR DNA vaccine, the
      efficacy of altering routes of administration and formulation of plasmid DNA was
      evaluated on the mouse lung tumor (LL2) naturally overexpressing endogenous EGFR
      in C57B6 mice. Three different combination forms were studied, including (1)
      intramuscular administration of non-coating DNA vaccine, (2) gene gun
      administration of DNA vaccine coated on gold particles, and (3) gene gun
      administration of non-coating DNA vaccine. LL2-tumor bearing C57B6 mice were
      immunized four times at weekly intervals with EGFR DNA vaccine. RESULTS: The
      results indicated that gene gun administration of non-coating xenogenic EGFR DNA
      vaccine generated the strongest cytotoxicity T lymphocyte activity and best
      antitumor effects. CD8(+) T cells were essential for anti-tumor immunity as
      indicated by depletion of lymphocytes in vivo. CONCLUSION: Thus, our data
      demonstrate that administration of non-coating xenogenic EGFR DNA vaccine by gene
      gun may be the preferred method for treating EGFR-positive lung tumor in the
      future.

PMID- 19178754
TI  - Hook worm caused chronic anemia found during the procedure of acute
      gastrointestinal bleeding: a case report.
AB  - BACKGROUND: Upper gastrointestinal bleeding with complicated factors is always
      difficult to find the primary origin. CASE PRESENTATION: Here we present a case
      of a 74-year-old male farmer suffered from acute upper gastrointestinal bleeding
      caused by gastric ulcer and Mallory-Weiss syndrome and chronic anemia which was
      at last found caused by hook worm infection. CONCLUSION: It tells us that
      considering multi-possibility when can not explain the symptom with monophyletism
      is very important for clinicians.

PMID- 19178755
TI  - Refractory cardiopulmonary failure after glyphosate surfactant intoxication: a
      case report.
AB  - BACKGROUND: Glyphosate is an herbicide considered to be of low toxicity to humans
      because its effects are specific to plants. However, fatal reactions to
      glyphosate have been reported after the ingestion of large amounts. Pulmonary
      edema, shock, and arrhythmia were the reported causes of mortality. CASE
      PRESENTATION: We present the case of a 57-year-old woman who was admitted to the
      emergency department unconsciousness after ingestion of glyphosate surfactant in
      a suicide attempt. Metabolic acidosis, refractory respiratory failure, and shock
      developed during hospitalization. Despite aggressive supportive care, the patient
      died in the hospital. CONCLUSION: The toxicokinetics of glyphosate surfactant is
      complicated. Respiratory failure, metabolic acidosis, tachycardia, elevated
      creatinine, and hyperkalemia are poor prognostic factors if presented. Physicians
      should consider using hemodialysis early to improve the outcome of patients with
      glyphosate surfactant intoxication.

PMID- 19178756
TI  - Can coverage of schistosomiasis and soil transmitted helminthiasis control
      programmes targeting school-aged children be improved? New approaches.
AB  - Control programmes generally use a school-based strategy of mass drug
      administration to reduce morbidity of schistosomiasis and soil-transmitted
      helminthiasis (STH) in school-aged populations. The success of school-based
      programmes depends on treatment coverage. The community-directed treatment
      (ComDT) approach has been implemented in the control of onchocerciasis and
      lymphatic filariasis in Africa and improves treatment coverage. This study
      compared the treatment coverage between the ComDT approach and the school-based
      treatment approach, where non-enrolled school-aged children were invited for
      treatment, in the control of schistosomiasis and STH among enrolled and non
      enrolled school-aged children. Coverage during the first treatment round among
      enrolled children was similar for the two approaches (ComDT: 80.3% versus school:
      82.1%, P=0.072). However, for the non-enrolled children the ComDT approach
      achieved a significantly higher coverage than the school-based approach (80.0
      versus 59.2%, P<0.001). Similar treatment coverage levels were attained at the
      second treatment round. Again, equal levels of treatment coverage were found
      between the two approaches for the enrolled school-aged children, while the ComDT
      approach achieved a significantly higher coverage in the non-enrolled children.
      The results of this study showed that the ComDT approach can obtain significantly
      higher treatment coverage among the non-enrolled school-aged children compared to
      the school-based treatment approach for the control of schistosomiasis and STH.

PMID- 19178757
TI  - The air's got to be far cleaner here: a discursive analysis of place-identity
      threat.
AB  - That talk is never disinterested complicates the relationship between the
      environment and the claims people make about it. Talk about place, and one's self
      in it, is particularly complex when the environment poses risk or is otherwise
      problematized. This study, a secondary analysis of interview data, seeks to
      extend discursive work on place-identity by examining the ways in which 14
      residents of a small English village talk about themselves and their locale. The
      locale accommodates an active quarry, and many residents had lodged complaints to
      the quarry about dust, noise and vibrations from blasting. Attention to the
      interactional context of the interviews illustrates the ways in which (simply)
      interviewing people about their locale can threaten self- and place-identity.
      When asked about life in the village, interviewees oriented to two main dilemmas
      in protecting self- and place-identity: (1) how to justify continued residence in
      a challenging environment and (2) how to complain about the locale whilst
      maintaining positive place-identity. Discursive responses to these dilemmas drew
      upon typical identity processes, such as self- and place distinctiveness and the
      formulation of out-groups, as well as upon constructions of localized power
      sharing and morally obligated tolerance of risk. We suggest that research on
      problematical places, and of environmental risk, needs to be sensitized to how it
      may constitute a threat to self- and place-identity, and how this may mediate
      formulations self and place, as well as of environmental risk.

PMID- 19178759
TI  - Review: doxorubicin delivery systems based on chitosan for cancer therapy.
AB  - OBJECTIVES: This review sheds insight into an increasingly popular polymer that
      has been widely explored as a potential drug delivery system. The abundant,
      biodegradable and biocompatible polysaccharide chitosan, with many other
      favourable properties, has been favoured as a drug delivery system for the
      purposes of encapsulating and delivery of doxorubicin with reduced side-effects.
      KEY FINDINGS: Doxorubicin is frequently used as a frontline chemotherapeutic
      agent against a variety of cancers. It has largely been able to demonstrate anti
      tumour effects, though there are major shortfalls of doxorubicin, which include
      serious side-effects such as cardiomyopathy and myelosuppression, and also an
      ever-present danger of extravasation during drug administration. In view of this,
      drug delivery systems are currently being explored as alternative methods of drug
      delivery in a bid to more effectively direct doxorubicin to the specific lesion
      site and reduce its systemic side-effects. Liposomes and dendrimers have been
      tested as potential carriers for doxorubicin; however they are not the focus of
      this review. SUMMARY: Recent advancements in doxorubicin and chitosan technology
      have shown some preliminary though promising results for cancer therapy.

PMID- 19178758
TI  - Stereotype content model across cultures: towards universal similarities and some
      differences.
AB  - The stereotype content model (SCM) proposes potentially universal principles of
      societal stereotypes and their relation to social structure. Here, the SCM
      reveals theoretically grounded, cross-cultural, cross-groups similarities and one
      difference across 10 non-US nations. Seven European (individualist) and three
      East Asian (collectivist) nations (N=1,028) support three hypothesized cross
      cultural similarities: (a) perceived warmth and competence reliably differentiate
      societal group stereotypes; (b) many out-groups receive ambivalent stereotypes
      (high on one dimension; low on the other); and (c) high status groups
      stereotypically are competent, whereas competitive groups stereotypically lack
      warmth. Data uncover one consequential cross-cultural difference: (d) the more
      collectivist cultures do not locate reference groups (in-groups and societal
      prototype groups) in the most positive cluster (high-competence/high-warmth),
      unlike individualist cultures. This demonstrates out-group derogation without
      obvious reference-group favouritism. The SCM can serve as a pancultural tool for
      predicting group stereotypes from structural relations with other groups in
      society, and comparing across societies.

PMID- 19178760
TI  - Stability of oleuropein in the human proximal gut.
AB  - OBJECTIVES: We aimed to assess the intralumenal stability of oleuropein in human
      gastric and small intestinal contents. We additionally aimed to assess the
      stability characteristics of oleuropein in media simulating the intralumenal
      conditions. METHODS: The intralumenal stability of oleuropein was assessed in
      aspirates from the stomach and the upper small intestine of healthy volunteers
      collected under both fasted and fed state conditions and in media simulating the
      intralumenal environment. KEY FINDINGS: Oleuropein degraded in aspirates
      collected in the fasted state. When the initial concentration was about 50
      microg/ml (close to expected intragastric concentration after single dose of
      commercially available products of oleuropein) the mean zero-order half-life of
      oleuropein in aspirates collected from the fasted small intestine was estimated
      to be 3.14 +/- 0.08 h at 37 degrees C (i.e. after oral administration in the
      fasted state, a substantial fraction of oleuropein degrades before reaching the
      intestinal mucosa). In contrast, oleuropein was stable in aspirates collected
      from the fed stomach; in small intestinal contents aspirated in the fed state the
      estimated zero-order degradation half-life was at least 12 h. CONCLUSIONS: These
      data suggest that oleuropein should not have substantial intralumenal stability
      problems when administered in the fed state. Data collected in media simulating
      the intragastric and intraintestinal environment suggest that pH affects the
      stability of oleuropein only at low pH values (of about 2). At higher pHs
      degradation characteristics are at least partly affected by the presence of other
      scavengers of reactive oxygen species in the medium.

PMID- 19178761
TI  - Novel mucoadhesive nasal inserts based on chitosan/hyaluronate polyelectrolyte
      complexes for peptide and protein delivery.
AB  - OBJECTIVES: The purpose of this study was the preparation and characterisation of
      mucoadhesive nasal inserts based on chitosan/hyaluronate polyelectrolyte
      complexes prepared at various pHs and at different molar ratios. METHODS: A
      suspension of chitosan/hyaluronate complexes with or without the model drugs
      (vancomycin or insulin) was lyophilised into small inserts. Complexation yield,
      FT-IR spectra and thermogravimetric analysis were used to study the degree of
      interactive strength between polyions. In-vitro swelling, mucoadhesion and
      release tests were performed in order to investigate delivery of vancomycin and
      insulin in the nasal cavity. KEY FINDINGS: The results indicated that the
      selection of complex preparative conditions allows modulation of insert swelling
      and mucoadhesion ability. Nasal inserts containing vancomycin or insulin had
      showed completely different drug release behaviour. CONCLUSIONS:
      Chitosan/hyaluronate polyelectrolyte complexes can be used for the formulation of
      mucoadhesive nasal inserts for the delivery of peptide and protein drugs.

PMID- 19178762
TI  - Metabolism of captopril carboxyl ester derivatives for percutaneous absorption.
AB  - OBJECTIVES: To determine the metabolism of captopril n-carboxyl derivatives and
      how this may impact on their use as transdermal prodrugs. The pharmacological
      activity of the ester derivatives was also characterised in order to compare the
      angiotensin converting enzyme inhibitory potency of the derivatives compared with
      the parent drug, captopril. METHODS: The metabolism rates of the ester
      derivatives were determined in vitro (using porcine liver esterase and porcine
      ear skin) and in silico (using molecular modelling to investigate the potential
      to predict metabolism). KEY FINDINGS: Relatively slow pseudo first-order
      metabolism of the prodrugs was observed, with the ethyl ester displaying the
      highest rate of metabolism. A strong relationship was established between in
      vitro methods, while in-silico methods support the use of in-vitro methods and
      highlight the potential of in-silico techniques to predict metabolism. All the
      prodrugs behaved as angiotensin converting enzyme inhibitors, with the methyl
      ester displaying optimum inhibition. CONCLUSIONS: In-vitro porcine liver esterase
      metabolism rates inform in-vitro skin rates well, and in-silico interaction
      energies relate well to both. Thus, in-silico methods may be developed that
      include interaction energies to predict metabolism rates.

PMID- 19178763
TI  - Pectin/Kollicoat SR30D isolated films for colonic delivery [I]: a comparison of
      normal and colitis-induced models to assess the efficiency of microbially
      triggered drug delivery.
AB  - OBJECTIVES: The purpose of the study was to evaluate digestion of
      pectin/Kollicoat SR30D free films for colonic delivery in vitro and in vivo.
      METHODS: Free films containing different ratios of pectin to Kollicoat SR30D were
      prepared by casting/solvent evaporation method. An in-vitro comparison of
      swelling, degradation and permeability of the free films was carried out in
      simulated colon fluids containing caecal contents from normal rats with colitis
      induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) or oxazolone. A comparative
      in-vivo evaluation of degradation was also conducted in normal and colitis
      induced model rats. KEY FINDINGS: The pectin within the mixed films was
      susceptible to rat colonic bacterial enzymes. The extent of digestion correlated
      with the amount of pectin present within the film. In vitro, the swelling index,
      drug permeability and extent of film digestion in simulated colon fluids with
      caecal contents obtained from normal rats were higher than from TNBS- or
      oxazolone-induced model rats, whereas in-vivo degradation was similar in the
      three groups of rats. The pectin/Kollicoat SR30D free films were completely
      degraded in the colitis-induced rats. CONCLUSIONS: Pectic/Kollicoat SR30D films
      may be useful as coatings to target delivery of drugs to the colon.

PMID- 19178764
TI  - Coumarins permeability in Caco-2 cell model.
AB  - OBJECTIVES: The presence of coumarins in human diet, their multiple
      pharmacological properties and occurrence in various herbal remedies represent
      significant reasons to explore their membrane permeability, as a first event
      contributing to coumarins oral bioavailability. Thus, we evaluated the
      permeability and cytotoxicity of 18 coumarins, with different substitution
      patterns involving OH, OCH3 and CH3 groups. METHODS: A modified Caco-2
      permeability model was used, in which the permeability test is performed with a
      robotic workstation and cells are grown on 96-well plates for 7 days. KEY
      FINDINGS: All studied coumarins were highly permeable, with calculated Papp
      values that varied within 4.1 x 10(-5) to 2.1 x 10(-4) in apical to basolateral
      studies and within 1.8 x 10(-5) to 7.0 x 10(-5) in basolateral to apical studies.
      The efflux ratio remained in all cases below 1. It was demonstrated that the type
      and position of substituents contributed more to the permeability than the number
      of substituents. CONCLUSIONS: The results allowed us to predict that these
      coumarins are well absorbed in the gut lumen and efflux is not limiting the
      absorption. Five coumarins had an influence on the mitochondrial function of Caco
      2 cells (1 < 80%, 4 > 120%), according to the WST-1 cytotoxicity test, but this
      does not seem to affect the permeability of the compounds.

PMID- 19178765
TI  - In-vitro sulfation of piceatannol by human liver cytosol and recombinant
      sulfotransferases.
AB  - OBJECTIVES: The aim of this study was to investigate the concentration-dependent
      sulfation of piceatannol, a dietary polyphenol present in grapes and wine and
      known for its promising anticancer and anti-inflammatory activity. METHODS:
      Sulfation of piceatannol was investigated in human liver cytosol as well as using
      a panel of recombinant sulfotransferase isoforms. Furthermore, the chemical
      structures of novel sulfates were identified by liquid chromatography/mass
      spectrometry (LC/MS). KEY FINDINGS: In the presence of 3'-phosphoadenosine-5'
      phosphosulfate, three metabolites could be detected whose structures were
      identified by LC/MS/MS as piceatannol disulfate (M1) and two monosulfates (M2,
      M3). The kinetics of M1 formation exhibited a pattern of substrate inhibition
      with a Ki of 21.8 +/- 11.3 microm and a Vmax/Km of 7.63 +/- 1.80 microl/mg
      protein per min. Formation of M2 and M3 showed sigmoidal kinetics with apparent
      Km and Vmax values of 27.1 +/- 2.90 microm and 118.4 +/- 4.38 pmol/mg protein per
      min, respectively, for M2; and 35.7 +/- 2.70 microm and 81.8 +/- 2.77 pmol/mg
      protein per min, respectively, for M3. Incubation in the presence of human
      recombinant sulfotransferases (SULTs) demonstrated that M1 was formed equally by
      SULT1A1*1 and SULT1B1 and to a lesser extent by SULT1A1*2. M2 was preferentially
      catalysed by SULT1A1*2, 1A3 and 1E1. The formation of M3, however, was mainly
      catalysed by SULT1A2*1 and SULT1A3. CONCLUSIONS: Our results elucidate the
      importance of piceatannol sulfation in human liver, which must be taken into
      account in humans after dietary intake of piceatannol.

PMID- 19178766
TI  - Distribution of fibroblast growth factor-2 (FGF-2) within model excisional wounds
      following topical application.
AB  - OBJECTIVE: To characterise the magnitude and distribution of fibroblast growth
      factor-2 (FGF-2) following topical application in hypromellose gel and film
      formulations or a solution in an animal wound model, in order to assess the
      potential of this route for treatment of chronic wounds. METHOD: Topical
      formulations of FGF-2 were applied to punch biopsy wounds, and FGF-2 levels
      within the wound measured. Each 12 mm diameter wound received 0.3 microg FGF-2 in
      solution, a 7% (w/w) hypromellose gel, a dried hypromellose film on Melolin
      backing or a saline control. After 2, 5 or 8 h the wounds were horizontally
      dissected into four sections (surface granulation, subcutaneous fat, superficial
      muscle and deep muscle) which were then analysed for FGF-2 concentration using
      ELISA. Confocal microscopy was used to evaluate the distribution of FGF-2 within
      the wound. KEY FINDINGS: There were significant differences in the mean FGF-2
      levels with respect to formulation and time following application (P < 0.05). FGF
      2 penetrated faster into tissue when formulated as a solution than as a gel or a
      film. There did not appear to be a significant difference between the gel and the
      film with respect to total concentrations achieved in the tissue, although
      confocal microscopy showed differences in FGF-2 distribution within the wound.
      CONCLUSIONS: Delivery of FGF-2 to wounds in a solution gave the greatest increase
      in tissue FGF-2 concentration when measured by ELISA and visualised using
      confocal microscopy. Gel and film formulations prolonged the release of FGF-2
      into the wound, although FGF-2 levels were not significantly different from
      controls when measured by ELISA. Confocal microscopy highlighted the differences
      in the penetration and distribution of the FGF-2 within the wound when released
      from different formulations.

PMID- 19178767
TI  - Oxidative stress, nitric oxide and prostaglandin E2 levels in the
      gastrointestinal tract of aging rats.
AB  - OBJECTIVES: To evaluate the presence of oxidative stress and alterations in the
      levels of two cytoprotective agents, prostaglandin E2 and nitric oxide, in the
      gastrointestinal tract of aging rats. METHODS: The production of superoxide
      anion, lipid peroxides, levels of superoxide dismutase and catalase, and
      production of prostaglandin E2 and nitric oxide in the stomach and duodenum of
      rats were determined at 1.5, 3, 12, 18 and 24 months of age. KEY FINDINGS:
      Oxidative stress was present in the stomach of the old rats (24 months), whereas
      prostaglandin E2 and nitric oxide production remained stable at 18 and 24 months.
      In the duodenum, no oxidative stress was observed at 24 months, but at 18 months,
      an increase in superoxide anion levels was detected. Prostaglandin E2 remained
      constant in the aged rats but nitric oxide decreased significantly at 24 months.
      CONCLUSIONS: The absence of macroscopic gastric injury throughout the
      gastrointestinal tract indicates that the oxidative stress in the stomach and the
      significant decrease of nitric oxide in the duodenum in the old rats are not
      sufficient to disrupt the mucosal defence network. The results support the notion
      that the disruption of the mucosal network is essentially regulated by the
      cytoprotective agents prostaglandin E2 and nitric oxide, and that injury appears
      only when both substances are concurrently reduced.

PMID- 19178768
TI  - Hydrogen sulfide protects from intestinal ischaemia-reperfusion injury in rats.
AB  - OBJECTIVES: Hydrogen sulfide (H2S) is an endogenously gaseous mediator,
      regulating many pathophysiological functions in mammalian cells. H2S has been
      shown to inhibit myocardial ischaemia-reperfusion (I/R) injury. However, little
      is known about whether H2S could modulate intestinal I/R injury. This study aimed
      to investigate the effect of H2S on intestinal I/R injury and potential
      mechanism(s) underlying the action of H2S in regulating the development of
      intestinal I/R injury in rats. METHODS: Following surgical induction of
      intestinal I/R injury for 1 h, groups of Sprague-Dawley rats were treated with,
      or without, tetramethylpyrazine (8 mg/kg), or sodium hydrosulfide (NaHS, an H2S
      donor at 7 or 14 micromol/kg) 30 min after occlusion. All rats were sacrificed
      immediately after the reperfusion. Their intestinal injury, together with that of
      sham-control rats, was histologically examined and their sera and intestinal
      malondialdehyde (MDA), superoxide dismutase (SOD), peroxidase (GSH-Px) activities
      were characterized by biochemical analysis. KEY FINDINGS: The results showed that
      NaHS significantly reduced intestinal I/R injury and the levels of sera and
      intestinal MDA activity, and dramatically increased the levels of serum and
      intestinal SOD and GSH-Px activity. CONCLUSIONS: The results suggest that H2S
      protects from intestinal I/R injury in rats, which is associated with increase in
      the activity of antioxidant enzymes.

PMID- 19178769
TI  - Effect of Guanxin No.2 decoction on gene expression in different areas of the
      myocardial infarcted heart of rats using microarray technology.
AB  - OBJECTIVES: We have used microarray technology to detect the effect of Guanxin
      No.2 decoction on gene expression in different areas of the myocardial infarcted
      heart of rats. METHODS: Male Sprague-Dawley rats (180-200 g) were randomly
      divided into three groups: sham-operated; coronary artery ligation; and coronary
      artery ligation plus administration of Guanxin No.2 decoction (10.0 g raw
      materials/kg per day by gavage). The experiment was carried out on day seven
      after ligation. KEY FINDINGS: We found that the gene expression using microarray
      technology showed many differences in the border infarcted left ventricular area
      compared with the remote noninfarcted left ventricular area after administration
      of Guanxin No.2 decoction. CONCLUSIONS: Guanxin No.2 decoction has a long history
      in treating ischaemic cardiomyopathy in China, but the molecular mechanism has
      been unclear. In this study we found that some important genes may have
      contributed to the cardioprotective effect of Guanxin No.2 decoction.

PMID- 19178770
TI  - Ozone oxidative post-conditioning in acute renal failure.
AB  - OBJECTIVES: The ischaemia-reperfusion process is largely mediated by reactive
      oxygen species. Taking into account that a transient and controlled
      administration of ozone is able to upregulate cellular antioxidant enzymes, a
      morphological, biochemical and functional renal study was performed in rats
      undergoing warm renal ischaemia. METHODS: Rats were divided into four groups. All
      except the negative controls underwent 60 min' bilateral renal ischaemia followed
      by 10 days' reperfusion. The positive control group received no further
      treatment. The ozone group received an ozone/oxygen mixture (ozone dose 0.5
      mg/kg) immediately after the ischaemia and daily for the 10 days' reperfusion;
      the oxygen group were given the same concentration of oxygen alone (13 mg/kg).
      Biochemical parameters fructosamine, phospholipase A2, catalase, superoxide
      dismutase and thiobarbituric acid reactive substances were measured, as well as
      renal plasma flow and glomerular filtration rate. KEY FINDINGS: Renal plasma flow
      and glomerular filtration rate decreased significantly in the positive controls
      and the oxygen group whereas values in the ozone group were similar to those in
      the negative control group. With respect to the biochemical parameters, ozone
      maintained a homeostasis redox, with significant increases in catalase and
      superoxide dismutase activities and similar values for phospholipase A2 and
      fructosamine compared with the negative control group. Fewer morphological
      alterations were seen in kidneys from the ozone group. No advantages were
      obtained in the positive control and oxygen groups. CONCLUSIONS: The protective
      effect of ozone may be explained by upregulation of the antioxidant defence
      system and beneficial effects on blood circulation and in oxygen metabolism.
      Ozone treatment may represent a therapeutic approach for minimising renal damage
      after transplantation.

PMID- 19178771
TI  - Strontium fructose 1,6-diphosphate alleviates early diabetic testopathy by
      suppressing abnormal testicular matrix metalloproteinase system in streptozocin
      treated rats.
AB  - OBJECTIVES: Male hypogonadism is frequently associated with testopathy in
      patients with type 2 diabetes and in middle-aged males. We hypothesized that
      abnormal matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in
      testis have large roles to play in male hypogonadism. It has been found in
      diabetic rats that a novel compound, strontium fructose 1,6-diphosphate (FDP-Sr),
      with extra high energy supply, could reverse male hypogonadism by normalizing MMP
      9 and TIMPs in the testis. We investigated whether FDP-Sr could be promising in
      treating diabetic testopathy. METHODS: Adult male Sprague-Dawley rats were
      administered a single dose of streptozocin (65 mg/kg, i.p.) to induce diabetes.
      The diabetic rats were treated with FDP-Sr in three doses or testosterone
      propionate in the final four weeks during the eight-week study. KEY FINDINGS:
      Serum testosterone, activity of marker enzymes, and mRNA of MMPs and TIMPs and
      protein of MMP-9 in the testis were detected. After eight weeks, the activity of
      acid phosphatase, lactate dehydrogenase, succinate dehydrogenase and g-glutamyl
      transpeptidase in testis were significantly decreased (P < 0.01), accompanied by
      down-regulated mRNA and activity of MMP-2 and MMP-9 (P < 0.01) and upregulated
      mRNA of TIMP-1 and TIMP-2. Downregulated MMP-9 protein and degenerative changes
      in histology were predominant in diabetic testis. CONCLUSIONS: FDP-Sr or
      testosterone propionate significantly normalized expression and activity of the
      MMPs-TIMPs system to attenuate changes in serum testosterone, marker enzymes and
      histology in testis. Effects of FDP-Sr were dose-dependent and comparable with
      those of testosterone propionate. By supplying extra energy, FDP-Sr could be
      promising in treating diabetic testopathy by normalizing abnormal MMP-9 and its
      endogenous inhibitors in testes.

PMID- 19178772
TI  - Animal studies supporting the inhibition of mast cell activation by Eriobotrya
      japonica seed extract.
AB  - OBJECTIVES: The potent antioxidant activity of Eriobotrya japonica seed extract
      (ESE) and its usefulness in the prevention and treatment of various disorders has
      been reported previously. Its antioxidant activity associated with beta
      sitosterol and polyphenols contained in the extract was also validated. In this
      study, anti-allergic activity of Eriobotrya japonica seed extract was
      investigated. METHODS: The inhibition of histamine release-mediated type 1
      allergy by Eriobotrya japonica seed extract was used as an index. KEY FINDINGS:
      The administration of this extract inhibited histamine release from rat mast
      cells, suggesting its usefulness in allergic disease treatment. In an experiment
      using a guinea-pig allergic rhinitis model, this extract reduced the frequency of
      sneezing and nose-scratching. CONCLUSIONS: These results suggest that Eriobotrya
      japonica seed extract may contribute to the relief of allergic disease-related
      symptoms.

PMID- 19178773
TI  - Antiulcerogenic and anti-inflammatory activities of the essential oil from
      Pterodon emarginatus seeds.
AB  - OBJECTIVES: The objective of this work was to investigate the antiulcerogenic and
      anti-inflammatory activities of the essential oil from Pterodon emarginatus
      seeds. METHODS: The following tests were used: ulcers induced by ethanol,
      indometacin and HCl/ethanol, and pleurisy induced by carrageenan in Swiss albino
      rats. The rats were treated by the oral route with essential oil of P.
      emarginatus seeds. KEY FINDINGS: The essential oil at 100, 300 and 500 mg/kg
      exhibited significant protection against ulcers induced by ethanol, indometacin
      and HCl/ethanol (P < 0.001). The essential oil caused a marked reduction in the
      exudate volume and inhibited leucocyte and neutrophil influx (P < 0.05) in
      carrageenan-induced pleurisy. Moreover, the essential oil significantly decreased
      nitric oxide (NO) and interleukin-1 (IL-1) levels, without affecting tumour
      necrosis factor-alpha production. CONCLUSIONS: The results demonstrated the
      marked antiulcerogenic and anti-inflammatory effects of the essential oil from P.
      emarginatus, which are, at least in part, a consequence of NO and IL-1
      modulation. P. emarginatus or its constituents might represent new therapeutic
      options to treat gastric ulcers and inflammatory diseases.

PMID- 19178774
TI  - Relaxing effects of Valeriana officinalis extracts on isolated human non-pregnant
      uterine muscle.
AB  - OBJECTIVES: This study investigated the relaxing effects of Valeriana officinalis
      L. (Valerianaceae) on human uterine muscle. The major uses of this species in
      Europe are as a sedative and an anxiolytic; it is also used as a spasmolytic to
      treat gastrointestinal spasm. METHODS: We evaluated two valerian extracts
      (ethanolic and aqueous) in comparison with a natural mixture of valepotriates and
      nifedipine on spontaneous and agonist-induced contractions in non-pregnant human
      myometrium in vitro. Qualitative and quantitative chemical analysis was used to
      correlate the chemical composition of extracts with their spasmolytic effects.
      Myometrial strips were obtained from hysterectomy specimens of premenopausal
      women. Longitudinal muscle strips were mounted vertically in tissue baths under
      physiological conditions to record their isometric contraction. The responses of
      cumulative concentrations of valerian extracts on spontaneous contractions in the
      presence and absence of the beta-adrenoceptor blocker atenolol or the
      cyclooxygenase inhibitor indometacin, and on agonist-induced contractions, were
      investigated. KEY FINDINGS: Valerian extracts and valepotriates inhibited uterine
      contractility in a concentration-dependent manner. Pretreatment with either
      atenolol or indometacin did not affect the uterine responses to valerian
      extracts. Valerian extract reduced the maximal contractile response induced by
      acetylcholine, phenylephrine and histamine independent of the stimulus.
      CONCLUSIONS: Valerian extracts may have direct inhibitory effects on the
      contractility of the human uterus and this justifies the traditional use of this
      plant in the treatment of uterine cramping associated with dysmenorrhoea.

PMID- 19178775
TI  - Anti-African trypanocidal and antimalarial activity of natural flavonoids,
      dibenzoylmethanes and synthetic analogues.
AB  - OBJECTIVES: The known anti-protozoal activity of flavonoids has stimulated the
      testing of other derivatives from natural and synthetic sources. METHODS: As part
      of our efforts to find potential lead compounds, a number of flavonoids isolated
      from Neoraputia paraensis, N. magnifica, Murraya paniculata, (Rutaceae),
      Lonchocarpus montanus, L. latifolius, L. subglaucescens, L. atropurpureus, L.
      campestris, Deguelia hatschbachii (Leguminosae), dibenzoylmethanes from L.
      subglaucescens and synthetic analogues were tested for in-vitro activity against
      chloroquine-sensitive Plasmodium falciparum and Trypanosoma brucei rhodesiense
      bloodstream form trypomastigotes. An assay with KB cells has been developed in
      order to compare in-vitro cytotoxicity of flavonoids with a selective action on
      the parasites. KEY FINDINGS: Thirteen of the compounds tested had IC50 values
      ranging from 4.6 to 9.9 microm against T. brucei rhodesiense. In contrast, a
      small number of compounds showed significant activity against P. falciparum;
      seven of those tested had IC50 values ranging from 2.7 to 9.5 microm. Among the
      flavones only one had IC50 < 10 microm (7.6 microm), whereas against T. brucei
      rhodesiense seven had IC50 < 10 microm. Synthetic dibenzoylmethanes were the most
      active in terms of number (five) of compounds and the IC50 values (2.7-9.5
      microm) against P. falciparum. CONCLUSIONS: Dibenzoylmethanes represent a novel
      class of compounds tested for the first time as antimalarial and trypanocidal
      agents.

PMID- 19178776
TI  - Injuries from external causes: progress in data management, analysis, and patient
      care.

PMID- 19178777
TI  - The establishment of injury surveillance systems in Colombia, El Salvador, and
      Nicaragua (2000-2006).

PMID- 19178778
TI  - [An information system for injuries from external causes (SILEX): a successful
      project in El Salvador].
AB  - This article examines the stages in developing an information system for injuries
      from external causes (Sistema de Informacion de Lesiones de Causa Externa-SILEX),
      as well as its limitations and achievements. SILEX is a Web-based application for
      collection, quality control, presentation, and analysis of data available from
      the hospital system for surveillance of injuries from external causes created by
      Ministry of Health of El Salvador with data from the hospital emergency services.
      This system maintains comprehensive information on the injured person-type of
      injury, intention, injury site, activity being performed at the time of injury,
      risk factors, etc.-in the form of tables, graphs, and maps, which streamlines the
      development of intervention plans and prevention initiatives for these types of
      injuries in El Salvador. This experience is an example of what can be done to
      close the information gap on injuries by external causes in the Region of the
      Americas.

PMID- 19178779
TI  - Violence-related injury in emergency departments in Brazil.
AB  - OBJECTIVE: This article describes the characteristics of violence-related injury
      (VRI) cases presenting at emergency departments (EDs) in Brazil and compares
      circumstances for assault-related and self-inflicted cases. METHODS: The study is
      cross-sectional. The data describe cases seen in September 2006 in 62 EDs,
      representing all 26 states and the Federal District. A total of 4 835 case
      records were analyzed. Basic statistical tabulations were complemented by
      logistic regression analysis to assess potential associations between type of
      violence (assault or self-harm) and multiple factors. RESULTS: Males comprised
      72.8% of cases while those aged 20 to 29 comprised 35.4%. Alcohol use was
      reported or suspected in 42.7% of cases, more commonly among males. Assault
      victims comprised 91.4% of cases versus self-inflicted injuries, which accounted
      for 8.6%. Three-fourths of the assault victims were male, while over half of the
      self-inflicted injury victims were female. The leading mechanism for assaults was
      physical force/blunt objects (46.2%), whereas poisoning was the predominant
      mechanism for self-inflicted injuries (71.4%). Younger females were significantly
      more likely to have been victims of self-inflicted injuries than younger males,
      while younger males were more likely to have been victims of assault; this
      finding is more pronounced in cases where alcohol use was reported. Self
      inflicted injuries were significantly more likely to occur in residences, while
      assaults were more likely to occur away from home. CONCLUSION: These results can
      improve understanding of the scope and characteristics of VRIs in Brazil (and
      thus contribute to national injury prevention efforts), and help identify areas
      for future research.

PMID- 19178780
TI  - Interpersonal violence in three Caribbean countries: Barbados, Jamaica, and
      Trinidad and Tobago.
AB  - OBJECTIVES: This article reports the prevalence of two types of interpersonal
      violence (IPV) (sexual and physical) and one type of aggression (psychological)
      in three low-to-middle-income Caribbean countries. It examines IPV among
      adolescents and young adults as both victims and perpetrators. METHOD: This
      population-based study compares the experiences of 15-30 year olds in countries
      at different levels of socioeconomic development. The Revised Conflict Tactics
      Scales (CTS2) and other behavioral instruments were used to assess the level and
      characteristics of IPV. RESULTS: Out of 3 401 respondents, 70.9% reported
      victimization by some form of violence, which was most commonly perpetrated by a
      relationship partner (62.8%). Sexual violence victimization was reported more
      commonly by women, and was highest in Jamaica. Significant between-country
      differences in overall levels of reported physical violence, and psychological
      aggression, were evident when stratifying by perpetrator type. CONCLUSIONS: The
      very high levels of reported IPV indicate very high levels of tolerance among
      victims, and suggest a culture of violence and of adversarial intimate
      relationships may be well entrenched. The findings support the view that co
      occurrence of general interpersonal violence and partner violence may be limited,
      and that one may not necessarily be a predictor of the other. They also reveal
      that, among partners, not only are there no gender differentials in victimization
      by physical violence, but more women than men are self-reporting as perpetrators
      of this type of IPV.

PMID- 19178781
TI  - [Trends in mortality from drowning, Mexico, 1979-2005].
AB  - OBJECTIVE: To examine the trends in mortality from drowning in Mexico and each of
      its federal states during the period from 1979-2005. METHODS: Mortality rates and
      trends were estimated for the study period from Mexico's official data based on
      the International Classification of Diseases, 9th and 10th revisions. Results
      were analyzed by age group, sex, and year registered, as well as by state and
      size of city or town of residence. RESULTS: From 1979-2005, there were 107 319
      deaths by drowning registered. The mortality from drowning rate decreased 65.31%
      (from 6.58 per 100 000 inhabitants in 1979-1981 to 2.28 per 100 000 inhabitants
      in 2003-2005). This decrease was evident in all the age groups (ranging from
      68.10% among 5-9 year olds to 54.30% among 1-4 years) and by state (ranging from
      87.19% in Colima to 36.58% in Nayarit). During the three-year period from 2003
      2005, drowning mortality was relatively greater among men and boys than among
      women and girls (rate: 5.46 (95%CI: 5.15-5.80); among the age groups 1-4 years
      (4.27 per 100 000) and 60 years or older (3.37 per 100 000 inhabitants); in the
      Tabasco state (5.92 per 100 000 inhabitants); and among towns with fewer than 2
      499 inhabitants (4.03% per 100 000 inhabitants). CONCLUSIONS: In Mexico, the
      drowning mortality drowning rate is on a downward trend, although it remains a
      serious public health problem. Intensified efforts are needed to harness
      information regarding accidentals death from this cause, both from the
      epidemiological surveillance angle as well as through the implementation of
      eradicating interventions.

PMID- 19178782
TI  - [Emergency care for victims of accidents and violence in Brazil].
AB  - OBJECTIVE: To analyze positive results, challenges, limitations, and potential
      benefits associated with the Brazilian Policy for the Reduction of Morbidity and
      Mortality due to Accidents and Violence (PNRMAV) with regard to hospital
      emergency and urgent care services. METHODS: From 2004-2007, a study was carried
      out in four Brazilian state capitals and the Federal District. The following
      areas were evaluated: the availability of standard practices for managing victims
      of accident or violence; availability and quality of adult and pediatric
      intensive care beds; patient management training for health care professionals;
      communication among the health care areas to provide better care to victims; and
      structure and organization of hospital services. The study included an
      exploratory stage, fieldwork, analysis, and dissemination of data. Both
      quantitative (absolute and relative frequencies) and qualitative methods
      (analysis of interactions between explicit and inferred information from
      statements and field records) were employed in the analysis. RESULTS: The study
      revealed positive results from the implementation of PNRMAV. The following focal
      areas were identified: (1) the need to invest in the response capacity of primary
      care services, (2) the importance of strengthening and promoting the emergency
      and urgent care network, (3) the importance of investing in appropriate equipment
      and of planning maintenance so that availability is not impacted, and (4) the
      need to invest in continuing education for health care professionals.
      CONCLUSIONS: The partial success obtained with PNRMAV shows that it is possible
      to include the topic of violence and accidents in the public health agenda and to
      implement life-promoting strategies at different levels.

PMID- 19178783
TI  - [Participatory development of descriptors for evaluation of violence and accident
      prevention centers in Brazil].
AB  - OBJECTIVE: To explain the participatory model used to develop descriptors for
      evaluating the Accident and Violence Prevention Centers created by the Ministry
      of Health of Brazil to initiate and follow-up on public policies that reduce
      morbidity and mortality due to external causes. METHOD: The nominal group
      technique was the main strategy employed. Participants included 13
      representatives from centers in the states of Rio de Janeiro and Espirito Santo.
      RESULTS: Eleven descriptors were identified for evaluation, with five being
      selected as priorities: situation analysis; intra- and intersectoral processes;
      monitoring of municipal accident and mortality data; political, financial, and
      administrative support (autonomy); and establishment of a work team (composition,
      dedication, and technical skills). CONCLUSIONS: The participatory model revealed
      both a step toward identity-developing for the centers, as well as the history of
      the health sector's actions in this area. The process also highlighted old
      barriers that must be overcome if effective actions against violence are to be
      taken by the country.

PMID- 19178784
TI  - Child delinquency and the prophylaxis of crime in early 20th-century Latin
      America.

PMID- 19178785
TI  - The possible role of human milk nucleotides as sleep inducers.
AB  - Breast-milk contains a potent mixture of diverse components, such as the non
      protein nitrogen fraction which includes nucleotides, whose variation in levels
      is evident throughout lactation. In addition, these substances play an important
      role in sleep homeostasis. In the present study, human milk samples were analyzed
      using a capillary electrophoresis system. The rhythmicity of each nucleotide was
      studied by cosinor analysis. It was found that the nucleotides 5'AMP, 5'GMP,
      5'CMP, and 5'IMP have significant (P < 0.05) circadian rhythms, the acrophases of
      the first two being during the night, and of the latter two during the day. While
      5'UMP did not show a clear circadian rhythm, there was an increase in its levels
      at night. In conclusion, the rise in nocturnal levels of 5'AMP, 5'GMP, and 5'UMP
      could be involved in inducing the 'hypnotic' action of breast-milk at night in
      the infant.

PMID- 19178786
TI  - Zinc intake during pregnancy increases the proliferation at ventricular zone of
      the newborn brain.
AB  - Neurogenesis involves cell proliferation, cell cycle arrest, differentiation,
      migration and the natural developmental death of the neural precursors. These
      processes are highly co-ordinated and governed by cell-cycle genes and neural
      transcription factors. Zn plays a crucial role as a functional and structural
      component of enzymes and transcription factors and components of the
      intracellular signaling pathway associated with the regulation of cell
      proliferation. The influence of additional Zn intake during pregnancy on the
      neuronal proliferation at ventricular zone of the developing fetus has been
      studied. Pups delivered by the group of mice provided with drinking water with
      4.0 mM Zn supplement throughout pregnancy contained an increased number of
      proliferating neurons in the ventricular zone at P0 compared to those delivered
      by the mice provided with drinking water without any Zn supplement. This finding
      provides direct evidence to support the notion that maternal Zn levels influence
      the development of the nervous system of the offspring.

PMID- 19178787
TI  - Maternal MTHFR 677C>T genotype and dietary intake of folate and vitamin B(12):
      their impact on child neurodevelopment.
AB  - Using the Bayley test, the mental and psychomotor development in a cohort of 253
      children were evaluated. Maternal dietary intake of vitamin B(12) and folate was
      assessed from a semiquantitative questionnaire administered during the first
      trimester of pregnancy. Maternal genotypes of MTHFR (677C>T and 1298A>C), were
      ascertained by PCR-RFLP. The 677T and 1298C variant alleles were present in 59%
      and 10% of participants, respectively. A dietary deficiency of vitamin B(12) was
      negatively associated with mental development (beta = -1.6; 95% CI = -2.8 to 
      0.3). In contrast, dietary intake of folate (< 400 mg/day) reduced the mental
      development index only among children of mothers who were carriers of the TT
      genotype (beta = -1.8; 95% CI = -3.6 to -0.04; P for interaction = 0.07). Vitamin
      B(12) and folate supplementation during pregnancy could have a favorable impact
      on the mental development of children during their first year of life, mainly in
      populations that are genetically susceptible.

PMID- 19178788
TI  - Caffeinated coffee enhances co-operative behavior in the Mixed Motive Game in
      healthy volunteers.
AB  - Caffeinated drinks are commonly consumed in social gatherings. However, their
      effects on social behavior remain unclear. The present study examined the effects
      of caffeinated coffee on antidepressant-related co-operative behavior. Seventy
      seven low-caffeine users took part in a randomized, double-blind, cross-over
      study of single dose of caffeinated coffee (150 mg caffeine) and decaffeinated
      coffee (9 mg caffeine) with at least a 3-day washout period. In each session,
      participants were asked to imagine a fictitious person and play the Mixed Motive
      Game with that person 45 min after coffee consumption. Heart rate, blood
      pressure, and state moods were measured at baseline and at 45 min post-coffee
      consumption. After caffeinated coffee, participants exhibited significantly
      higher blood pressure. They also allocated significantly fewer scores to
      themselves and sent significantly more sadness message during the game. These
      results suggest that caffeinated coffee may help to improve social support and
      depressive symptoms.

PMID- 19178789
TI  - Meal termination using oral sensory satisfaction: a study in non-obese women.
AB  - Non-obese individuals limit energy intake and maintain weight long-term.
      Knowledge of the mechanism they use to accomplish this could help in weight
      maintenance after weight loss and prevention of unneeded weight gain. The
      objective of the present study was to determine whether non-obese women use
      orosensory cues to limit short-term intake of high-energy density foods. Forty
      non-obese women consumed two high-energy rice puddings of equal energy density,
      one with high sugar and one with high fat. There were four study conditions.
      Participants ate until satisfied (basal), satisfied based on taste (taste),
      satisfied based on fullness (fullness) and while watching television
      (distraction). The participants were asked to refrain from eating and drinking
      after 2200. The treatments were done between 0830 and 0900. The order of
      treatments was randomized and all subjects completed all treatments. The quantity
      consumed and variation in hunger and taste intensity were the primary measures.
      Results were subjected to within subjects analysis of variance (ANOVA). Intake
      was significantly greater in the high-fat groups than in the high-carbohydrate
      groups (P = 0.0001). Study condition had a significant effect on intake (P =
      0.0000) with the taste condition generally resulting in the lowest intake. Hunger
      intensity significantly decreased after meal intake (P = 0.0156). There was a
      significant effect of condition (P = 0.0001) with base and taste conditions
      showing the greatest decrease. In the taste condition, specifically, the
      intensity of taste and hunger declined after intake (P = 0.0000). These results
      indicate that taste satisfaction can limit meal intake in non-obese women. Taste
      satisfaction could be a mechanism that is used to reduce food intake to
      compensate for previous excess consumption.

PMID- 19178790
TI  - The natural xanthone alpha-mangostin reduces oxidative damage in rat brain
      tissue.
AB  - The antiperoxidative properties of alpha-mangostin, a xanthone isolated from
      mangosteen fruit, were tested for the first time in nerve tissue exposed to
      different toxic insults. Two reliable biological preparations (rat brain
      homogenates and synaptosomal P2 fractions) were exposed to the toxic actions of a
      free radical generator (ferrous sulfate), an excitotoxic agent (quinolinate), and
      a mitochondrial toxin (3-nitropropionate). alpha-Mangostin decreased the
      lipoperoxidative action of FeSO(4) in both preparations in a concentration
      dependent manner, and completely abolished the peroxidative effects of
      quinolinate, 3-nitropropionate and FeSO(4) + quinolinate at all concentrations
      tested. Interestingly, when tested alone in brain homogenates, alpha-mangostin
      significantly decreased the lipoperoxidation even below basal levels. alpha
      Mangostin also prevented the decreased reductant capacity of mitochondria in
      synaptosomal fractions. Our results suggest that alpha-mangostin exerts a robust
      antiperoxidative effect in brain tissue preparations probably through its
      properties as a free radical scavenger. In light of these findings, this
      antioxidant should be tested in other neurotoxic models involving oxidative
      stress.

PMID- 19178791
TI  - Espresso coffee increases parasympathetic activity in young, healthy people.
AB  - Caffeine induces modifications of activity of the autonomic nervous system. This
      study analyzed the effect of a cup of espresso coffee on the heart rate
      variability (HRV) power spectral analysis, which is a method providing evaluation
      of the sympathetic and parasympathetic discharge. In young, healthy sedentary
      subjects (10 male, 10 female; aged 25-30 years), the HRV-power spectrum was
      evaluated over a period of 150 min after the administration of espresso coffee
      (caffeine, 75 mg) or decaffeinated coffee (caffeine, < 18 mg) in supine and
      seated position. Absolute values of the spectrum were summed in low (LF) and high
      frequencies (HF). The LF and HF spectra were used to estimate the sympathetic and
      parasympathetic activity, respectively. In the supine position, coffee increases
      HF, while decaffeinated coffee causes little modifications of HF. In the seated
      position, HF is not modified by coffee or decaffeinated coffee. Coffee and
      decaffeinated coffee do not induce any modification of LF in both positions. This
      experiment indicates that espresso coffee influences parasympathetic activity in
      the supine position.

PMID- 19178792
TI  - The efficacy of topical antibiofilm agents in a sheep model of rhinosinusitis.
AB  - BACKGROUND: Biofilms have been shown to be resistant to conventional antibiotic
      treatment. This study uses a sheep biofilm model developed by our department to
      investigate several novel topical anti-biofilm treatments. METHODS:
      Staphylococcal biofilms were grown in 54 sheep frontal sinuses over 8 days: Each
      sinus was randomized to (1) no intervention, (2) single mupirocin flush, (3)
      regular 12-hourly mupirocin flushes for 5 days, (4) Citric Acid Zwitterionic
      Surfactant (CAZS) via hydrodebrider, (5) gallium nitrate, (6) CAZS with gallium
      nitrate, (7) CAZS with mupirocin, and (8) saline regular flushes. Sheep were
      sacrificed and the sinus mucosa harvested 1 or 8 days after treatment to assess
      treatment and any biofilm regrowth. Confocal scanning laser microscopy was used
      to confirm the presence or absence of biofilms, and the extent of biofilm
      reduction was quantitated using fluorescent in situ hybridization and colony
      forming unit counts. RESULTS: In the control sheep biofilm coverage averaged
      31.7%. Saline and mupirocin b.d. washes for 5 days had 23% and 0.84% coverage,
      respectively, when harvested on day 8. A single mupirocin and gallium wash had
      7.7% and 16.2% on day 1 and 5.88% and 16.0% on day 8. CAZS with hydrodebrider had
      6.66% on day 1 but 21.95% on day 8 whereas CAZS with hydodebrider and gallium had
      13.3% on day 8. CONCLUSION: This study shows that regular treatment with
      mupirocin produced the most marked reduction in biofilm surface area coverage
      (0.84% and 1.25%) with sustained effects over the 8-day follow-up period.

PMID- 19178794
TI  - Analysis of T-helper responses and FOXP3 gene expression in patients with
      Japanese cedar pollinosis.
AB  - BACKGROUND: Evidence has been accumulated indicating that regulatory T (T-reg)
      cells play a crucial role in the maintenance of peripheral T-cell tolerance to
      allergens. To explore the role of FOXP3, which is required for the development of
      T-reg cells, in allergen-specific immune responses, we examined the relationship
      between the alteration of FOXP3 gene expression and in vitro immune responses
      against allergens. METHODS: Peripheral blood mononuclear cells obtained from 19
      human histocompatibility leukocyte antigens (HLA)-DPB1*0501 donors, including
      patients with Japanese cedar pollinosis and nonallergic healthy donors, were
      stimulated with Cry j 1 p61-75 peptide. On day 7, T cells were tested for peptide
      specific reactivity in IFN-gamma and interleukin (IL)-5 enzyme-linked immunospot
      (ELISPOT) assays. Real-time quantitative RT-PCR was performed to assess relative
      change of FOXP3 gene expression before and after in vitro stimulation.
      Neutralization assays using anti-glucocorticoid-induced tumor necrosis factor
      receptor family-related protein (GITR) and anti-IL-10 monoclonal antibody were
      also performed. RESULTS: Of 14 patients with allergic pollinosis tested, 10
      responders displayed T-helper type 2 (Th2)-polarized reactivity to Cry j 1 p61
      75, and 2 donors showed Th0 responses. Notably, the change of FOXP3 gene
      expression in donors showing peptide-specific T-helper responses was
      significantly lower than that in nonresponders, regardless of allergic
      pollinosis. CONCLUSION: Our data indicate that FOXP3 is functional in nonallergic
      healthy donors as well as allergic patients, and FOXP3-expressing T cells may be
      responsible for the down-regulation of allergen-specific T-helper responses in
      individuals. A better understanding of the nature and specificity of FOXP3
      expressing T cells in a suppressive mechanism is necessary to develop new
      immunotherapies against allergic rhinitis.

PMID- 19178793
TI  - Microarray analysis of distinct gene transcription profiles in non-eosinophilic
      chronic sinusitis with nasal polyps.
AB  - BACKGROUND: Recent literature has indicated the feasibility of microarray
      analysis in the characterization of chronic sinusitis. We hypothesized that
      previously unexplored inflammatory mechanisms would be involved in the
      pathophysiology of noneosinophilic chronic rhinosinusitis with nasal polyps (NE
      CRSwNP) and that this technology could be used to identify the gene expression of
      these novel and previously known mediators. METHODS: Patients with CRSwNP failing
      medical therapy were prospectively enrolled and NP tissue was removed at time of
      surgery. NE-CRSwNP was diagnosed based on clinical parameters including absence
      of allergic disease and confirmed with histopathology showing lack of
      eosinophilic infiltration. Messenger RNA (mRNA) transcripts extracted from study
      and control patients were then subjected to microarray analysis using Affymatrix
      based chips. Validation of findings was then confirmed via quantitative reverse
      transcription polymerase chain reaction (qRT-PCR). RESULTS: Microarray analysis
      revealed activation of pathways involved in antigen presentation, cellular
      movement, hematopoiesis, carcinogenesis, apoptosis, and cell signaling.
      Previously unexplored genes of interest were identified and their differential
      regulation was validated via qRT-PCR. Our data showed up-regulation of innate
      inflammation genes (IL-6, IL-8, and monocyte chemoattractant protein 1), hypoxia
      induced inflammation 1alpha, and fibrosis (tenascin) and lack of up-regulation of
      genes associated with allergic, eosinophilic inflammation (IL-4 and IL-13).
      Additionally, the genes for CXCL1 and autocrine motility factor receptor were
      novelly identified to be up-regulated. CONCLUSION: This study explores the
      utility of gene microarray technology in identifying unexplored targets of immune
      dysregulation in NE-CRSwNP. Furthermore, the data characterize the immunologic
      profile of NE-CRSwNP as it differs from other forms of CRSwNP, in particular,
      those known to be associated with eosinophilic inflammation.

PMID- 19178795
TI  - Pathophysiology of nasal polyposis: the role of desmosomal junctions.
AB  - BACKGROUND: Many mucosal inflammatory conditions are associated with alterations
      in epithelial intercellular junctions and barrier function; however, little is
      known about the role of intercellular junctions in inflammatory diseases of the
      upper airways. In this study, we examined nasal polyps for altered intercellular
      junctions and protein expression. METHODS: Biopsy specimens of nasal polyps and
      normal tissue were obtained intraoperatively from 11 patients and 6 controls.
      Tissue was analyzed for expression of intercellular junctional proteins by
      immunofluorescence. In parallel, cultured human bronchial epithelial (HBE) cells
      were treated with tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, and
      IL-13 to simulate inflammatory conditions followed by assessment for changes in
      junctional proteins by immunofluorescence and Western blot. RESULTS: Of the
      intercellular junctional proteins analyzed, including proteins comprising tight
      and adherens junctions, the only alterations observed were in desmosomal proteins
      in nasal polyp epithelium compared with normal controls. Specifically, expression
      of desmosomal proteins DSG2 and DSG3 were significantly decreased in polyps
      versus controls (0.53 pixel/microm2 versus 1.09 pixel/microm2 [p = 0.009], and
      0.29 pixel/microm2 versus 1.11 pixel/microm2 [p = 0.0078], respectively). In
      vitro experiments involving exposure of cultured HBE cells with inflammatory
      cytokines revealed that TNF-alpha treatment resulted in internalization and
      decreased expression of DSG2 by immunofluorescence and Western blotting.
      Treatment with IFN-gamma resulted in increased expression of DSG2 and evidence of
      protein cleavage by Western blot. IL-13 exposure resulted in down-regulation of
      DSG2 expression and evidence of protein cleavage. CONCLUSION: These results
      indicate that nasal polyps express decreased levels of DSG2 and DSG3 components
      of desmosomal junctions. This is likely linked to the mucosal inflammatory
      response. Exposure of a respiratory cell line to Th1/Th2 cytokines results in
      similar expressional alterations in DSG2, suggesting protein internalization and
      cleavage. We speculate that weakened desmosomal junctions in nasal mucosa
      secondary to inflammatory cytokines may contribute to the formation of nasal
      polyposis.

PMID- 19178796
TI  - Olfactory bulb volume in patients with sinonasal disease.
AB  - BACKGROUND: The aim of this study was to assess the volume of the olfactory bulb
      (OB) in patients with chronic rhinosinusitis (without nasal polyposis at the
      endoscopic evaluation) and to evaluate the correlation between this measure and
      the degree of sinonasal inflammation. METHODS: Patients with sinonasal disease
      (SND; n = 22) were compared with healthy controls (n = 16) using orthonasal and
      retronasal olfactory test results and OB volumes measurement calculated by
      planimetric manual contouring using standardized methods. The Lund-Mackay score
      (originally described for CT scan) was also used to gauge sinonasal inflammation
      (SND score). RESULTS: The two groups were not significantly different in terms of
      age or distribution of sex. Patients had significantly higher right- and left
      sided SND scores than controls. There was no significant group difference between
      patients and controls with regard to OB volume. However, patients with an SND
      score < or =12 had larger OB volumes than patients with higher SND scores (p <
      0.001). Even when controlling for the subjects' age, a significant correlation
      was present between OB volume and SND score (r = -0.52; p = 0.001) with smaller
      OB volumes being associated with a higher degree of sinonasal pathology.
      CONCLUSION: OB volume correlated with the SND score, which is an indicator of the
      degree of sinonasal inflammation. SND patients with a slight decrease or even
      normal olfactory function may already exhibit changes in their OB volume. This
      study also seems to emphasize the idea that OB volume changes are more sensitive
      to subtle changes in the olfactory system than results from psychophysical
      testing.

PMID- 19178797
TI  - Squamous metaplasia and chronic rhinosinusitis: a clinicopathological study.
AB  - BACKGROUND: The significance of squamous metaplasia (SM) in chronic
      rhinosinusitis (CRS) is unknown. The objectives of this study were to determine
      the prevalence of SM in histopathological specimens from patients with CRS and to
      correlate these histological findings with clinical features. METHODS: We
      reviewed the clinical records and pathological slides from 87 consecutive
      patients who underwent endoscopic sinus surgery for CRS. Demographic and clinical
      data, preoperative Chronic Sinusitis Survey (CSS) scores, and sinus CT stage were
      evaluated. Pathological slides were graded by a pathologist to characterize the
      degree of inflammation and SM, when present. CRS patients with and without SM
      were compared using student's t-test and chi2 test. RESULTS: Evaluation of the
      pathology slides revealed that 18.4% of specimens had SM present, whereas only
      2.2% of pathology reports noted this. Histological grading of chronic
      inflammation showed significantly greater severity in specimens with SM (n = 16)
      when compared with the cohort without SM (n = 75; 100.0% versus 77.5%,
      respectively; p = 0.016). There was no difference in preoperative CT stage or the
      presence of hyperostosis on imaging, CSS scores, duration of CRS symptoms, or
      other clinical features between those with SM and those without SM (p > 0.05).
      Immunodeficiency was the only comorbidity more prevalent in the metaplastic group
      (12.5% versus 0%, respectively; p = 0.003). CONCLUSION: SM is present in
      approximately 18% of routine CRS specimens. It has a positive correlation with
      the severity of inflammation noted histologically in CRS but does not correlate
      with disease severity or chronicity, clinically.

PMID- 19178798
TI  - Posttraumatic anosmia secondary to central nervous system injury.
AB  - BACKGROUND: The presumed pathogenesis of posttraumatic anosmia is stretching or
      shearing of the olfactory nerves in a coup-contracoup head contusion. Direct
      injury to the brain is an alternate mechanism of injury. In this study we report
      a case where direct injury to the brain is the probable mechanism of injury.
      METHODS: A case report was performed. RESULTS: A 55-year-old man presented with
      loss of smell beginning 1 month after a closed head injury with loss of
      consciousness. The MRI showed posttraumatic scarring in the region of the
      olfactory bulbs. CONCLUSION: This case suggests that central nervous system
      injury to the olfactory bulbs and tracts may be a mechanism of posttraumatic
      anosmia.

PMID- 19178799
TI  - Postoperative antibiotic care after functional endoscopic sinus surgery.
AB  - BACKGROUND: Antibiotics are used routinely in the postoperative care of
      functional endoscopic sinus surgery (FESS), but their efficacy has not been well
      evaluated. METHODS: Patients with chronic rhinosinusitis who underwent FESS were
      enrolled in this study. They were randomly divided into two groups: a study group
      and a control group. In the study group, patients took amoxicillin/clavulante for
      3 weeks after FESS. In the control group, no antibiotic was given after FESS.
      Before FESS, all patients filled out a symptom questionnaire and received nasal
      endoscopy. Swab specimens were taken from the middle meati for bacterial
      cultures. These procedures were done again 3 weeks after FESS. RESULTS: Seventy
      one patients completed the study. Thirty-one patients were in the study group,
      and 40 patients were in the control group. The symptom scores significantly
      decreased after surgery in both groups, but bacteria identified before and after
      FESS were statistically different in both groups. There were no differences in
      the symptom and endoscopic scores, rates of bacterial culture, and drug
      sensitivity to amoxicillin/clavulante between the two groups after FESS.
      CONCLUSION: This study showed that postoperative care with amoxicillin/clavulante
      did not improve the short-term outcome of FESS on chronic rhinosinusitis or
      decrease bacterial growth 3weeks after FESS, although the long-term influence was
      not evaluated in this study.

PMID- 19178800
TI  - Sonography versus plain x rays in diagnosis of nasal fractures.
AB  - BACKGROUND: The standard imaging procedure for suspected nasal fractures has been
      radiography (XR). However, its usefulness for clinical decision making is highly
      controversial. High-resolution ultrasonography now offers a promising new
      diagnostic imaging option. In this study we compared the diagnostic value of high
      resolution ultrasonography and conventional XR in the evaluation of suspected
      nasal fractures. METHODS: A prospective single-blinded study was performed.
      Ultrasound (US) and XR findings in 80 patients with suspected nasal fractures
      were compared with the definite clinical diagnosis with respect to sensitivity,
      specificity, and accuracy. RESULTS: For detection of fractures of the nasal
      dorsum, both modalities had high sensitivity (98 and 88% for US and XR,
      respectively) and specificity (95% for both US and XR). In lateral nasal wall
      fractures, specificity was higher for XR (75% versus 94%). Sensitivity was
      significantly higher for the US examination (98% versus 28%). In summary, the
      accuracy was higher for US. CONCLUSION: When available, US should be the first
      line imaging procedure in the evaluation of nasal fractures.

PMID- 19178801
TI  - Acoustic rhinometry of Asian noses.
AB  - BACKGROUND: Each ethnic group has different nasal cavity geometries. The
      reference value of the minimal cross-sectional area (MCA) and the nasal volume
      (NV) is mandatory for rhinologic evaluation in regular practice and for research.
      This study was designed to study the normal value of acoustic rhinometry (AR) in
      Asian subjects in comparison with other ethnic groups. METHODS: AR was performed
      in 135 healthy Thai subjects. Subjects were divided into two groups: group I,
      with normal anterior rhinoscopic appearance; group II included subjects with
      asymptomatic, slightly deviated nasal septa. RESULTS: The mean of the MCA was
      0.61 +/- 0.60 cm2 before decongestion and 0.64 +/- 0.14 cm2 after decongestion.
      The mean distance from the nostril to the point of MCA (D) was 1.66 +/- 0.59 cm
      before decongestion and 1.41 +/- 0.74 cm after decongestion. The mean of the NV
      measured between 0 and 4 cm was 3.66 +/- 0.67 cm3 before decongestion and 4.18 +/
      0.75 cm3 after decongestion. Before decongestion, there were no significant
      differences in the mean of the MCA, D, and NV between group I and group II
      subjects; however, there were significant differences in mean MCA and NV after
      decongestion. There were no differences in the parameters between male and female
      subjects before decongestion, except for the D, but after decongestion the mean
      values of the MCA, D, and NV were significantly higher in male subjects compared
      with female subjects. CONCLUSION: The results of this study can be used as a
      reference value for Asian ethnicities. Thai subjects had measurements comparable
      with those of the European study and somewhat different from the study in black
      populations.

PMID- 19178802
TI  - Balloon catheter dilatation for frontal sinus ostium stenosis in the office
      setting.
AB  - BACKGROUND: Frontal sinus ostium stenosis (FSOS) is problematic even for expert
      surgeons. Balloon catheter (BC) technology has been recently introduced to
      rhinology. The aim of this study is to assess technical feasibility and
      effectiveness of BC dilatation of FSOS in the office setting. METHODS: This
      retrospective, multi-institutional case series describes all patients who
      underwent BC dilatation of FSOS in the office setting in the year ending December
      31, 2007. RESULTS: Six adult patients underwent a total of seven BC dilatations
      of FSOS in the clinical setting. The pretreatment ostium size was 1-2 mm. Four of
      the dilatations were performed with a 5-mm lacrimal BC (LacriCATH, Quest Medical,
      Allen, TX) and three dilatations were executed with a 7-mm sinus BC (SinuCATH,
      Quest Medical). All procedures were performed using topical anesthesia only. No
      complications occurred. Five of the six dilated FSOS dilatations were deemed
      successful after one BC dilatation. One ostium contracted >50% and required
      repeat BC dilatation. All ostia have remained patent with a follow-up range of 4
      9 months. No subject has required formal surgical revision. CONCLUSION: This
      preliminary report describes BC of FSOS in the office setting. The technique may
      serve as a safe and feasible alternative, potentially avoiding formal revision
      sinus surgery in select patients.

PMID- 19178803
TI  - In vivo laser tissue welding in the rabbit maxillary sinus.
AB  - BACKGROUND: One of the challenges in the current expansion of endoscopic
      sinonasal surgery is the ability to adequately reconstruct the skull base. Laser
      tissue welding (LTW) uses laser energy coupled to a biological solder to produce
      tissue bonds with burst thresholds exceeding human intracranial pressure. This
      technology could be used to reduce the rate of postoperative cerebrospinal fluid
      (CSF) leak. We performed this study to determine whether LTW can create durable
      tissue bonds in sinonasal mucosa that support normal wound healing and produce
      minimal collateral thermal injury. METHODS: Bilateral maxillary sinus mucosal
      incisions were made in 20 New Zealand white rabbits and one side was repaired
      using LTW. Burst pressure thresholds were measured on postoperative days 0, 5,
      and 15 and were compared with control using a two- way ANOVA and a post hoc Tukey
      test. Welds were examined histologically for thermal injury, inflammation, and
      fibroplasia and graded on a 4-point scale by three blinded observers. RESULTS:
      The burst pressures of the LTW group were significantly higher than control on
      postoperative day 0 (120.85 mm Hg, N = 4, SD = 47.84 versus 7.85 mm Hg, N = 4, SD
      = 0.78), and day 5 (132.56 mm Hg, N = 8, SD = 24.02 versus 41.7 mm Hg, N = 8, SD
      = 7.2; p < 0.05). By postoperative day 15 there was no significant difference
      between LTW (169.64 mm Hg, N = 8, SD = 18.49) and control (160.84 mm Hg, N = 8,
      SD = 14.16) burst thresholds. There was no evidence of thermal injury to the
      surrounding tissue in any group as well as no difference between experimental
      group and control with respect to inflammation or fibroplasia. CONCLUSION: This
      is the first in vivo study showing that LTW is capable of producing tissue bonds
      exceeding human intracranial pressure with negligible thermal injury in sinonasal
      tissue. Welding can be performed endoscopically using a fiberoptic cable and may
      be useful in CSF leak and skull base repair.

PMID- 19178804
TI  - Attachment-oriented endoscopic surgical strategy for sinonasal inverted
      papilloma.
AB  - BACKGROUND: It is well documented that inverted papillomas (IP) have a localized
      attachment site. Still, instead of concentrating on the attachment site,
      endoscopic surgeons often perform an extended resection similar to the one
      achieved after external surgery. OBJECTIVE: Our objective was to evaluate an
      attachment-oriented endoscopic surgical strategy and to determine IP attachment
      diameter and location. METHODS: A prospective study was conducted. Thirty-three
      consecutive patients who underwent endoscopic IP excision (2001--2007) were
      enrolled. Thirty patients had adequate follow-up. Attachment diameters were
      measured in 25/33 patients. Surgery included debulking, identifying the precise
      mucosal attachment site, subperiosteal dissection and excision of the attachment,
      frozen section control, and resection/drilling of underlying bone. RESULTS: The
      mean measured attachment diameter (n = 25) was 8.4 +/- 6 mm (range, 3-23 mm).
      Attachment locations included maxillary sinus (39%), ethmoid sinus (21%), nasal
      cavity (21%), frontal sinus (6%), sphenoid sinus (6%), lamina papyracea (3%), and
      cribriform plate (3%). The mean follow-up (n = 30) was 40 +/- 21 months. Three
      patients had Krouse stage 1, 10 patients had stage 2, and 17 patients had stage
      3. Nine patients had undergone previous surgeries. After attachment-oriented
      endoscopic surgery, three patients had persistent disease. Nasolacrimal duct
      stenosis was the only complication (n = 1). CONCLUSION: Even advanced IP have
      small attachments. Their Identification facilitates efficacious resection with
      minimal morbidity.

PMID- 19178805
TI  - Combined image guidance and intraoperative computed tomography in facilitating
      endoscopic orientation within and around the paranasal sinuses.
AB  - BACKGROUND: The utility of image guidance (image-guided surgery [IGS]) and
      intraoperative computed tomography (CT) scanning as a tool for less experienced
      endoscopic surgeons to aid in localization of paranasal sinus and skull base
      anatomic structures was evaluated. METHODS: Partial endoscopic dissection was
      performed on cadaver specimens by three fellowship trained rhinologists. Anatomic
      sites within and around the sinuses were tagged with radio-opaque markers.
      Otolaryngology residents identified tagged anatomic sites using four successive
      levels of technology: endoscopy alone (simulating outpatient clinic), endoscopy
      plus preoperative CT (simulating endoscopic sinus surgery [ESS] without IGS),
      endoscopy plus IGS registered to preoperative CT (simulating current ESS with
      IGS), and endoscopy plus IGS registered to real-time intraoperative CT. Responses
      were graded as follows: consensus rhinologist answer (4 points), close answer
      without clinically significant difference (3 points), within anatomic region but
      definite clinical difference (2 points), outside of anatomic region (1 point), no
      answer (0 points). RESULTS: Eleven residents participated. Of 20 specific
      anatomic sites, IGS-intraoperative CT provided the most accurate anatomic
      identification at 16 sites. For 8 sites, IGS-intraoperative CT had a
      significantly higher score than endoscopy alone (p < 0.05; eta2 = 0.29-0.67). For
      6 sites, IGS-preoperative CT scan had a significantly higher score than endoscopy
      alone (p < 0.05; eta2 = 0.30-0.67). All participants found that IGS
      intraoperative CT scan made them most comfortable in identifying anatomy.
      CONCLUSION: Combined IGS and intraoperative CT scan technology may be an
      instructional adjunct for less experienced paranasal sinus surgeons for
      dissection and evaluation of unfamiliar or distorted anatomy.

PMID- 19178806
TI  - Construct validation of a low-fidelity endoscopic sinus surgery simulator.
AB  - BACKGROUND: Before a simulator becomes widely accepted, it must be relevant,
      affordable, and accessible. We have developed a low-cost model emphasizing the
      basic skills required for endoscopic sinus surgery (ESS). It is noninvasive, free
      from risk of infection, and an excellent low-pressure learning opportunity. The
      current study was designed to assess the construct validity of our simulator.
      METHODS: We conducted a stratified randomized crossover-control study.
      Otolaryngology residents, fellows, and faculty performed predetermined tasks on
      the model or cadaver, and then switched. Evaluation included hand motion
      analysis, task time, and blinded expert review. RESULTS: Sixteen subjects at
      various levels of training participated. Cadaver performance correlated well with
      level of training and previous experience with ESS. However, model performance
      did not demonstrate statistically significant correlation. CONCLUSION: Our model
      was unable to demonstrate clear construct validity at this time. Materials and
      structural modifications are in progress. Pending further validation, its low
      cost construction possesses potential for integration into otolaryngology
      residency curricula. Assessment of the simulator's ability to improve surgical
      skill is also planned.

PMID- 19178807
TI  - Analysis of transnasal endoscopic versus transseptal microscopic approach for
      excision of pituitary tumors.
AB  - BACKGROUND: The traditional method of pituitary tumor excision is transseptal
      microscopic excision; however, the transnasal transsphenoidal endoscopic approach
      has shown comparable results with the transseptal microscopic approach at some
      institutions. The objective of this study is to compare the two types of sellar
      and parasellar mass resection: transnasal transsphenoidal endoscopic excision
      versus transseptal microscopic excision. METHODS: A retrospective cohort analysis
      was performed on subjects who were referred to a tertiary hospital for surgical
      management of sellar or parasellar masses. The two groups of patients either
      underwent a transnasal endoscopic approach with endoscopic excision or
      transseptal microscopic excision. Demographics, tumor characteristics, operative
      details, length of hospital stay, intraoperative and postoperative complications,
      level of postoperative pain, recurrence rate, use of computed tomography (CT)
      image guidance, and length of follow-up were gathered. The data between the two
      groups were then compared. RESULTS: The analysis included 19 subjects who
      underwent endoscopic excision and 29 subjects who underwent transseptal
      microscopic excision. Null macroadenoma was the most common sellar mass followed
      by prolactinoma. There were no statistical differences in rates of perioperative
      complications and suprasellar or cavernous sinus invasion. Patients who underwent
      an endoscopic approach had shorter operative times, lower estimated blood loss,
      less lumbar drain use, less pain, and a shorter postoperative hospital stay (p <
      0.05). CONCLUSION: The two approaches show similar intraoperative characteristics
      and immediate complication rates. Transnasal transsphenoidal endoscopic excision
      is a reasonable alternative to the traditional method of sellar mass excision.

PMID- 19178808
TI  - Comparison of laryngeal mask with endotracheal tube for anesthesia in endoscopic
      sinus surgery.
AB  - BACKGROUND: The purpose of this study was to compare surgical conditions,
      including the amount of intraoperative bleeding as well as intraoperative blood
      pressure, during functional endoscopic sinus surgery (FESS) using flexible
      reinforced laryngeal mask airway (FRLMA) versus endotracheal tube (ETT) in
      maintaining controlled hypotension anesthesia induced by propofol-remifentanil
      total i.v. anesthesia (TIVA). METHODS: Sixty normotensive American Society of
      Anesthesiologists I-II adult patients undergoing FESS under controlled
      hypotension anesthesia caused by propofol-remifentanil-TIVA were randomly
      assigned into two groups: group I, FRLMA; group II, ETT. Hemorrhage was measured
      and the visibility of the operative field was evaluated according to a six-point
      scale. RESULTS: Controlled hypotension was achieved within a shorter period using
      laryngeal mask using lower rates of remifentanil infusion and lower total dose of
      remifentanil. CONCLUSION: In summary, our results indicate that airway management
      using FRLMA during controlled hypotension anesthesia provided better surgical
      conditions in terms of quality of operative field and blood loss and allowed for
      convenient induced hypotension with low doses of remifentanil during TIVA in
      patients undergoing FESS.

PMID- 19178809
TI  - Results of endoscopic maxillary mega-antrostomy in recalcitrant maxillary
      sinusitis.
AB  - BACKGROUND: In patients with chronically diseased maxillary sinuses, poor
      mucociliary clearance may result from long-standing inflammation or scarring from
      previous surgery. This subset of patients often has persistent sinus disease
      despite medical therapy and adequate antrostomy. Endoscopic maxillary mega
      antrostomy (EMMA) is a mucosal sparing technique that facilitates mucus clearance
      and sinus irrigation in terminally dysfunctional maxillary sinuses. EMMA involves
      extending the antrostomy through the posterior half of the inferior turbinate
      down to the floor of the nose, creating a significantly enlarged antrostomy. This
      study describes our results of EMMA in recalcitrant maxillary sinusitis. METHODS:
      A retrospective review was performed of patients who underwent EMMA for
      recalcitrant maxillary sinusitis between July 2005 and September 2007. We studied
      diagnoses, comorbid factors, clinical efficacy, revision rate, and complications.
      RESULTS: Twenty-eight patients (average age, 48 years) underwent 42 EMMAs for
      recalcitrant maxillary sinusitis. Average follow-up was 11 months. All patients
      had previous maxillary sinus surgery (mean = 2.3). Relevant comorbid factors
      included prior Caldwell-Luc or maxillofacial surgery (16/42), cystic fibrosis
      (11/42), asthma (11/42), and IgG deficiency (3/42). The most common symptoms
      reported were facial pain/pressure and purulent rhinorrhea. At the time of the
      most recent postoperative examination, 74% of patients reported complete
      resolution of symptoms while 26% reported partial symptomatic improvement. There
      were no complications and the revision rate was 0%. CONCLUSION: Maxillary sinuses
      that appear to be terminally diseased may be rehabilitated surgically without the
      need for surgical stripping. EMMA is an effective and safe treatment option for
      the management of recalcitrant maxillary sinus disease.

PMID- 19178811
TI  - The effect of nasal surgery on snoring.

PMID- 19178813
TI  - The influence of galvanic currents and voltage on the proliferation activity of
      lymphocytes and expression of cell surface molecules.
AB  - Release of metal ions from dental metal fillings supported by galvanism can cause
      local or general pathological problems in sensitive and genetically susceptible
      individuals. We aimed to investigate in vitro lymphocyte responses and expression
      of surface molecules influenced by galvanic currents and voltage. Human
      peripheral blood lymphocytes were influenced by galvanic currents and voltages
      and lymphocyte proliferation was measured. Control samples were not exposed to
      the influence of galvanism. We also studied the expression of surface molecules
      by the FACS analysis. A 15-h and shorter influence of almost all tested currents
      and voltages caused a significant decrease in lymphocyte proliferation and the 15
      h influence of 20 microA currents significantly increased expression of surface
      molecules CD 19, 11a/18, 19/69 and 19/95. An influence of 10 and 3 microA
      currents led to a significant decrease in the expression of surface molecules CD
      3, 11a/18, 3/69 and 3/95 and to a significant increase in CD 19 expression. An 80
      mV voltage influence led to a significant decrease in the expression of surface
      molecules CD 3, 11a/18, 3/69, 3/95, 19/69 and 19/95, and 200 and 300 mV voltages
      significantly decreased the expression of surface molecules CD 3, 19, 11a/18,
      3/95 and 19/95 and significantly increased CD 19/69 expression. A long-lasting
      influence of galvanism can, in sensitive and genetically susceptible individuals,
      influence lymphocyte proliferation and surface molecule expression. The threshold
      for pathological values of 5 microA for galvanic currents and 100 mV for galvanic
      voltage was confirmed.

PMID- 19178812
TI  - Expression of endothelial and inducible nitric oxide synthase and caspase-3 in
      tonsillar cancer, chronic tonsillitis and healthy tonsils.
AB  - Neoangiogenesis and inhibition of apoptosis are two factors considered as major
      leading causes of tumorigenesis. NO, synthesized by NOS, plays an important role
      in tumour growth, dissemination and vascularization. Caspase-3 is an executive
      enzyme of apoptosis. The presented research work has been focused on the
      comparative evaluation of localization of the angiogenic and proapoptotic
      cytokines expressed in tonsillar diseases. The immunohistochemical reaction of
      eNOS, iNOS and caspase-3 in tonsillar cancer (N = 17), chronic tonsillitis (N =
      11) and clinically healthy tonsils (N = 8) was detected. High eNOS occurrence in
      endothelial cells of highly vascularized regions in tonsillar cancer, variable
      eNOS expression in the vessels of lamina propria in chronic tonsillitis and high
      expression in the cytoplasm of endothelial cells of small veins in healthy
      tonsillar tissue was ascertained. Increased iNOS expression was found in cancer
      tissue in comparison with the healthy tonsils. Nevertheless, the highest
      expression of iNOS was found in chronic tonsillitis. Higher expression of caspase
      3 was discovered in germinal centres of lymphoid follicles of the chronic
      tonsillitis tissue. However, the positivity in the interfollicular zone and
      surface squamous epithelium was weak only. Merely isolated caspase-3-positive
      cells were found in tonsillar cancer. Very low expression of caspase-3 was
      detected in the lymphatic follicles of the healthy tonsils. Research results
      showed high expression of eNOS in the carcinomatous tissue. The eNOS expression
      in chronic tonsillitis confirms its role in regulating the lymphocyte
      circulation. Low expression of caspase-3 in malignant epithelial cells of
      tonsillar cancer shows decreased capability of apoptosis compared to chronic
      tonsillitis tissue, where apoptosis seems to be rather frequent and concentrated
      in the germinal centres of lymphatic follicles. The differences in localization
      of eNOS and caspase-3 expression between benign and malignant processes may be a
      promising tool for precise morphological distinction of chronic inflammation and
      tumours.

PMID- 19178814
TI  - Effect of paternal rat irradiation transmitted to the progeny during prenatal
      development.
AB  - The transgenerational transmission of radiation damage was investigated on the
      basis of quantitative changes of nucleic acids and histones, the integral index
      of tissue and organ cellularity. Male Wistar rats, whole-body irradiated with the
      dose of 3 Gy of gamma rays, were mated with non-irradiated females 25 or 80 days
      after exposure and their progeny were investigated on the 15th (embryos), 17th
      (embryos), or 19th (embryonic brain) day of prenatal development (E15, E17, and
      E19Br, respectively). A significant increase in DNA and RNA concentration and
      content was found on the 15th day and predominantly on the 17th day of gestation
      in the progeny of males irradiated 80 days before mating. On the contrary, in the
      progeny of the same males, concentration of histones was decreased in groups E15
      and E19Br. Finally, the radiation alterations in the progeny arisen from
      irradiated spermatogonia (by paternal exposure 80 days before mating) were more
      profound in nucleic acids than in histones. Our findings suggest an incidence of
      radiation-induced genome instability manifested as enhanced proliferating
      activity of cells in response to DNA damage in the progeny of males, mated at
      later intervals after exposure.

PMID- 19178815
TI  - Lack of B-RAF mutations in head and neck squamous cell carcinoma.
AB  - B-RAF is one of the most commonly mutated oncogenes in human cancer. However, the
      mutation status of B-RAF has not been established completely in HNSCC. We have
      analysed the mutation status of the kinase domain of the B-RAF gene (exons 11 and
      15) in 91 Japanese HNSCC patients as well as 12 HNSCC cell lines. DNA was
      extracted and amplified by PCR. Mutations were then analysed by SSCP mutation
      detection method. Since V600EB-RAF constitutes 90 % of the mutations identified
      in B-RAF in human cancers, we also used MASA analysis to specifically detect this
      mutation in exon 15 of B-RAF. Using both methods, no mutation was found in both
      exon 11 and 15 in all patients and cell lines. Mu tations are absent or rare in
      the kinase domain of B-RAF in Japanese HNSCC. However, more studies are still
      needed to determine its usefulness as a target for molecular therapy in these
      patients.

PMID- 19178816
TI  - A novel method for the estimation of podocyte injury: podocalyxin-positive
      elements in urine.
AB  - Podocytes form an outer aspect of the glomerular capillary wall and play a
      decisive role in its permeability for macromolecules. The main podocyte surface
      antigen podocalyxin, a highly electronegative sialoglycoprotein, prevents the
      podocyte foot processes from collapsing. Podocyte damage in glomerular disease is
      supposed to be accompanied by podocyte detachment, and shed podocytes and their
      fragments (marked by podocalyxin) may be identified in the urine. Using anti
      podocalyxin monoclonal antibody, PCX+EL were counted by FACS in 38 patients with
      various types of active glomerulonephritis, 15 patients with chronic
      glomerulonephritis in long-term remission and 44 healthy controls. Urinary levels
      of PCX+EL were significantly higher in patients with active glomerulonephritis
      compared to patients with chronic glomerulonephritis in longterm remission (93 +/
      100 vs. 6.3 +/- 3.2/microl of urine, P < 0.000001) and healthy controls (4.4 +/-
      2.6/microl of urine, P < 0.000001 compared to active glomerulonephritis, n.s.
      compared to chronic glomerulonephritis in longterm remission). These preliminary
      data suggest the potential of this simple method to monitor the activity of
      glomerular disease. Further prospective studies of larger cohorts of patients
      with individual glomerular diseases are clearly warranted.

PMID- 19178828
TI  - [Effects of environmental factors on children's health].

PMID- 19178831
TI  - [Effects of prenatal exposure to stress and lead on spatial learning and memory
      development in rats].
AB  - OBJECTIVE: To explore the effects of prenatal exposure to stress and lead on
      spatial learning and memory development in rats. METHODS: All 32 Sprague-Dawley
      (SD) pregnant rats were divided randomly into 4 groups, 8 per group in line with
      the Random Number Table. The four groups were: no maternal stress, no Pb exposure
      (NS/C); non-maternal stress, Pb exposure (NS/L), maternal stress, no Pb exposure
      (S/C), and maternal stress plus Pb exposure (S/L). The spatial learning and
      memory ability, the serum corticosterone level both pre and post-testing of 30
      day old offsprings, and lead concentration in hippocampus were tested by means of
      Morris Water Maze, radioimmunoassay and Inductively Coupled Plasma Mass
      Spectrometry (ICP-MS). RESULTS: The residence time of male and female in NS/L was
      (16.08+/-3.41) s, (15.72+/-3.33) s, which were significantly shorter than NS/L
      (25.42+/-4.76) s, (24.55+/-4.43) s and S/C (20.96+/-3.45) s, (20.65+/-2.98) s,
      and significant difference was observed in the joint exposure effect (F=5.478,
      P<0.05). The effect of the joint exposure was significant on post-testing serum
      corticosterone. The hippocampus lead concentrations of NS/L and S/L were
      (0.4378+/-0.1041) microg/g and (0.4679+/-0.1243) microg/g without significant
      differences (F=0.298, P>0.05). CONCLUSION: Prenatal joint exposure to restraint
      stress and lead might increase the effects of single exposure on the spatial
      learning and memory ability and serum corticosterone level of offsprings, and the
      joint influence on corticosterone level might be one of the reasons of further
      impairment of learning and memory.

PMID- 19178832
TI  - [Study on maternal-fetal status of Pb, As, Cd, Mn and Zn elements and the
      influence factors].
AB  - OBJECTIVE: Trace and toxic elements have great influences on the fetus growth
      during the pregnancy. The status of Pb, As, Cd, Mn and Zn in maternal and
      umbilical cord blood and influence factors were analyzed. METHODS: From September
      2006 to April 2007, 130 pairs of maternal blood and cord blood in total were
      collected at the time of spontaneous delivery or cesarean section. At the same
      time, the development of newborn was measured immediately. The concentrations of
      elements were determined by inductively coupled plasma mass spectrometry, the
      relationship of these elements between maternal and cord blood were also
      analyzed. RESULTS: The median (microg/L) concentration of blood Pb, As, Cd, Mn
      and Zn in maternal blood were 64.32, 3.81, 0.84, 54.26 and 6312.50. And the
      median (microg/L) of those elements in cord blood were 35.72, 2.84, 0.32, 78.99
      and 2250. The levels of Cd (r=0.341, P=0.000) and As (r=0.552, P=0.000) in
      maternal blood were positively correlated with the elements in the cord blood.
      From the questionnaire we conclude that the occupational hazardous factors and
      room decorated were the risk factors for the blood As and Zn levels. After
      multilinear regression analysis we also found mother weight, occupational
      hazardous factors and mother systolic pressure might affect the levels of blood
      Mn, Zn, As and Cd. CONCLUSIONS: The levels of these elements were affected by
      environmental and maternal factors. In this study, although the levels of all
      heavy metals in pregnant women were below those considered hazardous, however,
      they were still higher than those in the developed countries. The effects of
      heavy metals of maternal exposure on developing fetuses should deserve attention
      further.

PMID- 19178833
TI  - [Lead levels in children after 10-year use of unleaded gasoline in Guangzhou
      municipality].
AB  - OBJECTIVE: To investigate the blood lead levels (BLLs) in children after 10-year
      use of unleaded gasoline in Guangzhou and evaluate the effect of this measure.
      METHODS: Through stratified random sampling method, 4 kindergartens and 4
      elementary schools were selected from each of three districts among 12 districts
      of Guangzhou. Totally 2373 children were recruited into this survey and 1-2 ml
      blood was sampled from each child through vein. The lead concentration in blood
      samples was determined with Inductively Coupled Plasma Mass Spectrometry (ICP-MS)
      after diluted with 0.1% Triton X-100 and 0.1% HNO(3) in the ratio of 1:20.
      RESULTS: Among 2373 children, the highest BLL was 330 microg/L, while the lowest
      was 10 microg/L. Geometric mean (GM) of BLL was 58.28 microg/L with 61.11
      microg/L of male and 55.37 microg/L of female (t=8.671, P=0.000). Sixty (2.51%)
      children were identified as elevated BLLs (>or=100 microg/L), including 36
      (2.90%) male and 24 (2.09%) female (chi2=1.594, P=0.207). Compared to the surveys
      conducted in China 10-year ago, the children with elevated BLLs decreased 96.28%
      and the GM of BLLs reduced 58.37%. BLLs in suburb children (60.33 microg/L) were
      higher than those in downtown (58.09 microg/L) or in countryside (56.72
      microg/L). CONCLUSION: The BLLs in children and the ratio for children with
      elevated BLLs, had declined dramatically after 10-year implement of unleaded
      gasoline in Guangzhou.

PMID- 19178834
TI  - [Lead distribution and 78,000 glucose regulated protein levels in various organs
      of weaned rats].
AB  - OBJECTIVE: To investigate lead distribution and the change of 78 000 glucose
      regulated protein (GRP78) in various organs of weaned rats challenged with low
      level maternal origin lead. METHODS: Male littermates, bred from the female
      Fisher 344 rats gavaged with lead acetate or sodium acetate (1 ml of 10 mg/ml per
      day per animal) with male Fisher 344 rats without lead treatment, were divided
      into 4 groups including control (group A), gestation plus lactation (group B),
      gestation only (group C), and lactation only (group D). Each group had 6 litters.
      These littermates were weaned and terminated at postnatal day 21. Lead contents
      and GRP78 levels in various organs of these littermates were determined by atomic
      absorbance spectrometry (AAS) and Western blotting analysis, respectively.
      RESULTS: Maternal lead was observed to transfer to littermates through gestation
      and lactation. Concentrations of littermate blood lead in groups A to D were
      (0.0010+/-0.0010), (0.1420+/-0.0190), (0.0250+/-0.0040), and (0.1490+/-0.0160)
      microg/ml, respectively. Concentrations of littermate brain lead in groups A to D
      were (0.0005+/-0.0005), (0.1120+/-0.0130), (0.0125+/-0.0042), and (0.0700+/
      0.0058) microg/g, respectively. Concentrations of littermate kidney lead in
      groups A to D were (0.0050+/-0.0050), (1.0400+/-0.1000), (0.1040+/-0.0330), and
      (0.9920+/-0.0850) microg/g, respectively. Concentrations of littermate liver lead
      in groups A to D were (0.0030+/-0.0050), (0.3600+/-0.0550), (0.0567+/-0.0126),
      and (0.3030+/-0.0310) microg/g, respectively. Blood, brain, kidney and liver lead
      concentrations in groups B and D were significantly higher than those in group C
      and differences were 5-10 folds. Arbitrary units of littermate leukocytic GRP78
      concentration normalized with actin protein in groups A to D were 1.000+/-0.038,
      1.180+/-0.060, 0.998+/-0.109, and 1.290+/-0.110, respectively. Arbitrary units of
      littermate brain GRP78 concentration normalized with actin protein level in
      groups A to D were 0.996+/-0.128, 0.922+/-0.246, 1.150+/-0.170, and 0.750+/
      0.126, respectively. CONCLUSION: Lead in maternal bodies could be transferred to
      litter bodies through gestation and lactation and distributed in various organs.
      Lead might also changed GRP78 expression in leukocytes.

PMID- 19178835
TI  - [Internet addiction among Shanghai adolescents: prevalence and epidemiological
      features].
AB  - OBJECTIVE: To study the prevalence of internet use and internet addiction in
      adolescents of Shanghai. METHOD: From September to October 2007, a total of 5135
      adolescents from 16 middle schools of 6 districts of Shanghai took part in the
      epidemiological study by a cross-sectional survey and 5123 adolescents finally
      enrolled in the study. A questionnaire of "DRM Adolescent Internet Use 52 Scale"
      was administrated to investigate the prevalence of internet use and internet
      addiction in adolescents of Shanghai. On this scale of 5-point rating, the scale
      includes seven parts of contents as tolerance, abstinence reaction, planning
      ability, self-control ability, whenness, sociability and hazard. RESULTS: The
      rate of internet use among the surveyed adolescents was 94.32% (4673/5123), among
      which the incidence rate of internet addiction was 8.78% (450/5123). Boys, senior
      middle-school students were more susceptible to internet addiction than girls and
      junior middle-school students (male scores 122.42+/-43.46, female scores 116.92+/
      38.10, F=23.22, P=0.00; senior middle-school students 125.24+/-39.02, junior
      middle-school students 110.30+/-42.35, F=164.68, P=0.00). Students from
      vocational senior middle-school were most susceptible (junior middle-school
      students 110.30+/-42.35, ordinary senior middle-school students 122.83+/-40.99,
      key senior middle-school students 120.05+/-37.87, vocational senior middle-school
      students 133.37+/-36.84, F=34.44, P=0.00). The 2nd grade students of senior
      middle-school have the highest risk for internet-addiction. CONCLUSION: The
      prevalence of internet use and internet addiction in adolescents of Shanghai
      should be comparatively high in China, which indicates that great attention
      should be paid to the prevention and control.

PMID- 19178836
TI  - [A study on the relationship between point mutation in pre-core region G1896A of
      hepatitis B virus and safety of breast feeding].
AB  - OBJECTIVE: To investigate the relationship between pre-core G1896A point mutation
      of hepatitis B virus (HBV) and safety of breast feeding. METHODS: Serum and
      breast milk samples were collected from 62 pregnant women of HBV DNA
      positive/HBeAg negative. PCR-solid phase hybridization was used to detect the
      point mutation in pre-core region G1896A of HBV from pregnant women, and HBV DNA
      loads in sera and breast milk were determined by fluorescence quantitative PCR
      (FQ-PCR). RESULTS: The prevalence of point mutation was 61.3% (38/62) in 62
      pregnant women with HBsAg positive/HBeAg negative. The positive rate of HBV DNA
      in breast milk of group with point mutation (28.9%) was similar to that of group
      without mutation (29.2%, chi2=0.0003, P>0.05). However, The positive rate of HBV
      DNA in breast milk of group with high HBV loads (56.0%) was significantly higher
      than that of group with low HBV loads (10.8%, chi2=14.79, P<0.01). CONCLUSION:
      The point mutation in pre-core region G1896A of HBV dose not affect the positive
      rate of HBV DNA in breast milk and higher HBV DNA loads in serum of pregnant
      women might increase the risk of mother-infant transmission.

PMID- 19178837
TI  - [Anti-atherosclerotic effect of betaine in apolipoprotein E-deficient mice].
AB  - OBJECTIVE: To study the effect of betaine on the formation of atherosclerotic
      plaque in apolipoprotein E (ApoE)-deficient mice and explore its anti
      inflammatory mechanism. METHODS: Seven-week-old ApoE-deficient mice (C57BL/6J
      background) were divided into four groups randomly based on body weight: model
      group and three betaine groups. Wild-type mice with the same age and genetic
      background were used as control group. The control group and model group were fed
      AIN-93G diet. Three betaine groups were fed AIN-93G diet supplemented with 1, 2,
      4 g betaine/100 g diet, respectively. Serum tumor necrosis factor-alpha (TNF
      alpha), monocyte chemoattractant protein-1, lipid levels and methylation status
      of TNF-alpha promotor in aorta were determined at 0, 7 and 14 weeks. The
      percentage of aorta sinus plaque to lumen area was measured at 14-week. RESULTS:
      The percentage of aorta sinus plaque to lumen area of 1% and 2% betaine groups
      were (11.43+/-2.65)% and (12.09+/-3.07)%, respectively, which were 41% and 33%
      smaller than that of the model group (t=3.117, 3.010, respectively, and P<0.01).
      Serum TNF-alpha level of three betaine groups were (56.33+/-3.86), (63.04+/-4.67)
      and (65.52+/-3.97) pg/ml, respectively, which were lower than that of the model
      group (79.40+/-4.68) pg/ml (t=9.270, 6.571 and 5.576, respectively, P<0.001), but
      there was no significant difference in the methylation status of TNF-alpha
      promotor among all five groups. CONCLUSION: Betaine could inhibit the development
      of atherosclerosis via anti-inflammation.

PMID- 19178838
TI  - [Relation between dietary patterns and insulin resistance in 40-59 years old
      Guangzhou adults].
AB  - OBJECTIVE: To evaluate the overall diet quality of adults in Guangzhou and
      investigate whether adherence to the Dietary Guidelines for Chinese Residents
      could help to reduce the risk of obesity and insulin resistance. METHODS: All 540
      adults aged 40-59 years completed 3 consecutive 24-hour diet recalls. Diet
      quality were evaluated by using Chinese Diet Balance Index (DBI) scoring and
      evaluating system. Anthropometric parameters, fast glucose and fast insulin were
      measured. Insulin resistance was defined as the highest quartile of the
      homeostasis model assessment scores. RESULTS: The DBI-Lower Bound Score (DBI
      LBS), DBI-Higher Bound Score (DBI-HBS) and DBI-Diet Quality Distance (DBI-DQD)
      were 16.1-17.5, 7.6-8.2, 23.6-25.7 relatively. The intake of cereals, beans and
      dietary products were insufficient in the population, while the intake of animal
      food, salt and edible oils were excessive. Subjects in model A had a lower body
      mass index (BMI, P=0.022) and waist-to-hip ratio (WHR, P=0.001) than those in
      model E. Compared with model A, subjects in model E had greater odds ratio for
      insulin resistance (odds ratio: 3.00; 95% CI: 1.21, 7.67). CONCLUSION: The
      dietary structure of the residents in Guangzhou was relatively balanced and
      reasonable, but the problems such as inadequate food intake and excessive food
      intake still co-exist. Adherence to the Dietary Guidelines for Chinese Residents
      could help to reduce the risk of insulin resistance.

PMID- 19178839
TI  - [Study of effects of dietary fatty acids on the serum lipids in
      hypercholesterolemic subjects].
AB  - OBJECTIVE: To study the effects of dietary fatty acids on the serum lipids in
      hypercholesterolemic subjects. METHODS: All 297 residents with
      hypercholesterolemia were enrolled in Guangzhou. The dietary composition and the
      changes in serum lipid levels during the 6-month follow-up were analyzed.
      RESULTS: (1) 297 subjects were enrolled and 281 subjects (88 male, 193 female)
      completed the 6-month follow-up. The serum TC concentration of the subjects was
      (6.09+/-0.68) mmol/L at baseline. (2) According to the percentage of energy from
      total fat, all of the subjects were divided into three groups, including total
      fat % en<25% (group I, 90 subjects), 25%-30% (group II, 97 subjects), >30% (group
      III, 94 subjects). The reduction of TC and LDL-C in group I and group II was
      greater than that in group III. (3) According to the percentage of energy from
      SFA, all of the subjects were divided into three groups, including SFA % en<7%
      (group I, 81 subjects), 7%-10% (group II, 129 subjects), >10% (group III, 71
      subjects). The reduction of TC and LDL-C in group I and group II was greater than
      that in group III. (4) All of the subjects were divided into three groups,
      according to the percentage of energy from MUFA, including MUFA % en<10% (group
      I, 93 subjects), 10%-13% (group II, 106 subjects), >13% (group III, 82 subjects).
      The reduction of TC and LDL-C in group II was greater than that in group I and
      group III. (5) All of the subjects were divided into three groups according to
      the percentage of energy from PUFA, including PUFA % en<7% (88 subjects), 7%-9%
      (94 subjects), >9% (99 subjects). No significant difference was found among the
      reduction of serum lipids in the three groups. CONCLUSION: Dietary total fat %
      en<or=30%, SFAs % en<or=10% and MUFAs % en 10%-13% should be conductive to reduce
      the serum lipids of patients with hyperlipidemia.

PMID- 19178840
TI  - [Detection and analysis of antibiotic resistance of Salmonella from retail meats
      in some districts of Shaanxi province].
AB  - OBJECTIVE: Salmonella isolates recovered from retail meats that were collected in
      supermarkets and free markets in Xi'an and Yangling areas of Shaanxi province
      were studied to determine antibiotic susceptibility. METHOD: Antimicrobial
      susceptibility to 14 antibiotics of 193 salmonella isolates were determined by
      using agar dilution method, which was recommended by National Committee of
      Clinical Laboratory Standard (NCCLS), and E.coli ATCC25922 and E.faecalis
      ATCC29212 as standard control strains. RESULTS: The 44.6% of the salmonella
      isolates were resistant to sulfamethoxazole, followed by resistance to kanamycin
      (40.9%), tetracycline (37.8%), amoxicillin (26.9%), ampicillin (25.4%),
      gentamicin (23.3%) and chloramphenicol (21.8%). Some isolates also showed
      resistance to fluoroquinolones, the rates for ciprofloxacin, enrofloxacin,
      levofloxacin and gatifloxacin were 22.3%, 21.8%, 20.8% and 21.2%, respectively.
      55 isolates (28.5%) were multidrug resistant (MDR) strains, 28 of 193 isolates
      (14.5%) could resist at least 13 antibiotics, 24 isolates (12.4%) were resistant
      to from 4 to 12 antibiotics. CONCLUSION: Salmonella isolates recovered from
      retail meats in Xi'an district of Shaanxi province were seriously resistant to
      antimicrobials commonly used as human and veterinary medicine.

PMID- 19178841
TI  - [The comparison study on effects of water-soluble components of fine particulate
      matter on vasomotor functions in aortas from rats after exposure in different
      time].
AB  - OBJECTIVE: To compare the difference of vasomotor functions in aortas segments
      from Wistar rats between 1-hour and 6-hours after exposure of water-soluble
      components of fine particulate matter (PM2.5). METHODS: All 30 Wistar rats were
      assigned to five groups (n=6 for each group) at random: the blank control group,
      control group for 1-hour and 6-hours, exposure group for 1-hour and 6-hours. The
      rats were sacrificed 1-hour or 6-hours later and aorta ring segments were mounted
      on wire myographs. RESULTS: (1) There was no significant difference in vasomotor
      functions among three control groups (P>0.05). (2) 1-hour or 6-hours after
      exposure there was a decrease of contraction elicited by 60 mmol/L KCl in
      contrast to the control group (P<0.05), whereas no significant change between the
      exposure group for 1-hour and 6-hours (P>0.05). (3) On the level of 10(-5) or 10(
      7) mol/L, 1-hour after exposure there was a decrease in endothelium-dependent
      acetylcholine (ACh) elicited relaxation precontracted by 10(-6) mol/L NE compared
      with the control group (P<0.01 or P<0.05), on the level from 10(-5) to 10(-7)
      mol/L there was a decrease compared with the exposure group for 6-hours (P<0.05),
      whereas no difference between the exposure group for 6-hours and the control
      group (P>0.05). On the level from 10(-5) to 10(-9) mol/L, 1-hour after exposure
      there was a decrease in endothelium-independent sodium nitroprusside (SNP)
      elicited relaxation precontracted by 10(-6) mol/L NE as compared with the control
      group (P<0.01 or P<0.05) and a decrease on the level of 10(-6) or 10(-9) mol/L
      compared with the exposure group for 6-hours (P<0.05), 6-hours after exposure a
      decrease was caused as compared with the control group on the level from 10(-5)
      to 10(-7) mol/L (P<0.01 or P<0.05). CONCLUSIONS: Inhibition of contraction and
      impairment of relaxation in aortas should be caused 1-hour after exposure to
      water-soluble components of PM2.5 in the air, which is weaken 6-hours after
      exposure.

PMID- 19178848
TI  - Gender activation in transparent and opaque words.
AB  - Two reaction time experiments were carried out to examine the morphological
      gender processing of Spanish words that were either transparent -that is, ending
      in o/a (e.g., banco - bank)-or opaque-that is, without superficial gender marking
      (e.g., virtud - virtue). In Experiment 1, participants categorized the gender of
      a transparent gender target preceded by a derived word of the same gender (e.g.,
      banquillo-dock, masculine) or of different gender (e.g., banqueta-stool,
      feminine). A negative priming gender effect indicates the use of strategic
      attentional mechanisms to decide the gender of the target, but also automatic
      computation of the prime gender. Experiment 2 used a lexical decision task with
      the stimuli of Experiment 1 in addition to opaque gender words. The results show
      longer reaction times for transparent gender words with regard to opaque items.
      This effect was possibly due to the lexical requirements of the task: lexical
      decision, and also because transparent words are morphologically more complex
      than opaque words. Finally, in both experiments, there was negative priming: when
      prime and target were of the same gender, reaction times were longer. This effect
      indicates that participants cannot ignore the gender of the prime when they
      respond to the target.

PMID- 19178849
TI  - Fictional characters' emotional state representation: what is its degree of
      specificity?
AB  - Story events are a psychological cause of emotional reactions, which in turn,
      motivate subsequent actions. This study addresses the degree of specificity of
      readers' inferences about fictional characters' emotions. In Experiment 1 (off
      line), participants read short stories and selected the emotional term that was
      more consistent with the protagonist's emotion. Results indicated that
      participants tended to favor the specific emotional word. In Experiment 2 (on
      line), reading times were longer when a target sentence described the protagonist
      in an emotional state that differed in family from the adequate emotional state,
      but belonged to the same class and valence of emotions, but no differences were
      found between emotions belonging to the same family. Overall, these results
      indicate that emotional inferences are more specific than valence and class, but
      not specific enough to differentiate subtleties within a family of emotions.

PMID- 19178850
TI  - [Non-verbal memory impairment in Alzheimer-type dementia: Forgetting or
      acquisition?].
AB  - Non-verbal memory impairment in Alzheimer-type dementia: Forgetting or
      acquisition?. The research aims to compare patients diagnosed with early
      Alzheimer's disease (AD) and unipolar major depression (D) with a healthy control
      group (HS) on diverse nonverbal memory tasks (NVM), recall of position, and
      recognition of abstracts designs. All participants completed a global protocol
      for diagnosis of dementia. The patients with early AD (n= 27) and D (n= 19) were
      compared with the healthy subject group (n= 30) on a standardised visuospatial
      learning test. The AD patients scored significantly lower than HS and D on NVM
      tasks, but there were no significant differences between AD and D on position
      recall. Furthermore, the AD group did not show faster forgetting rates on
      position recall or design recognition in comparison to HS and D groups. These
      results are interpreted in terms of neurocognitive processes that explain NVM
      impairment in AD and depression.

PMID- 19178851
TI  - [Visuospatial learning impairment in Parkinson Disease].
AB  - Visuospatial learning impairment in Parkinson Disease. Despite the fact that
      different mnesic processes have been found to be impaired in Parkinson's disease,
      spatial learning is still an unstudied aspect. The aims of the present study were
      to evaluate visuospatial and verbal learning in nondemented patients with
      Parkinson's disease (PD) (N= 20), and to assess the influence of processing
      speed, attention, working memory, and visuospatial perception. Compared to
      controls (N= 20), PD patients had a poorer performance on Spatial Span, Judgment
      Line Orientation Test (JLOT), and 8/30 SRT. No differences were found between
      patients and controls in other functions assessed. Regression analysis showed
      that performance on Spatial Span and JOLT explains 58.2% of the variance of total
      spatial learning. Our results suggest an early impairment of spatial working
      memory and visuospatial perception in patients with PD. The visuospatial learning
      impairment may result from a primary deficit in these functions. These results
      suggest a global affectation of visuospatial processes, which may arise from
      dysfunction of the cortico-striatal circuits that include prefrontal and
      posterior parietal cortex.

PMID- 19178852
TI  - The Roman High- and Low-Avoidance rat strains differ in fear-potentiated startle
      and classical aversive conditioning.
AB  - The Swiss sublines of Roman High-(RHA/Verh) and Low-(RLA/Verh) Avoidance rats
      have been genetically selected (and outbred) since 1972 because of their good
      versus extremely poor acquisition of two-way, active avoidance. Inbred strains
      (RHA-I and RLA-I), derived from those two lines, have been maintained at our
      laboratory since 1997. The RLA line/strain shows increased stress-induced
      endocrine responses and enhanced anxiety/fearfulness in a variety of
      unconditioned behavioural variables and tests. Thus far, however, the Roman rat
      strains have not been compared in procedures involving classical fear
      conditioning to cues or contexts. Therefore, the present work was aimed at
      comparing RHA-I and RLA-I rats in 1) two different procedures of fear-potentiated
      startle and 2) in a classical fear conditioning (i.e., conditioned freezing)
      paradigm. The results indicate that, compared to RHA-I rats, RLA-I animals
      display higher levels of conditioned fear (as measured either by startle
      responses or freezing behavior) across those different tasks.

PMID- 19178853
TI  - [Personality disorders in eating disorder patients].
AB  - Personality disorders in eating disorder patients. A follow-up study was designed
      to analyze the relation between personality disorders (PD) and the course of
      eating disorders (ED) in 34 patients who required treatment over 4 years and
      half. 91% of the clinical sample met the criteria for PD at the initial
      assessment and 36% at the end of treatment, with a significant reduction in MCMI
      II scores at follow-up. The outcome of the ED was significantly related to the PD
      outcome. There was a higher rate of improvement of PD in the bulimic group (61%)
      than in anorexic group (34%). The patients who presented schizoid and avoidant
      personality disorders were the most resistant and they adhered less to treatment.
      The prevalence of PD in the clinical sample and its relation to the course of ED
      from a person-centered model is discussed.

PMID- 19178854
TI  - [Clinical personality trait differences in the maintenance of abstinence and in
      relapses in the treatment of smoking cessation].
AB  - Clinical personality trait differences in the maintenance of abstinence and in
      relapses in the treatment of smoking cessation. The aim of this study is to
      describe and compare personality characteristics of participants who quit smoking
      voluntarily by means of group treatment. The assessment instrument used was the
      Millon Clinical Multiaxial Inventory (MCMI). It was administered to a sample of
      105 persons in Malaga (Spain) in The Spanish Cancer Association (Asociacion
      Espanola Contra el Cancer). The analysis consisted of comparing two sample
      groups: abstinence and relapse. The results revealed a higher rate of avoidant,
      masochistic and negativistic clinical personality traits in the relapse group.
      However, people with dependent personality traits maintained abstinence. There
      were also differences, in the direction of more relapses, in schizotypal and
      borderline personality disorders. This suggests that certain personality traits
      could be risk factors for relapse, whereas others increase the probability of
      success in the process of smoking cessation.

PMID- 19178855
TI  - [Family-based drug use prevention: the "Familias que Funcionan" ["Families that
      Work"] program].
AB  - Family-based drug use prevention: The <<Familias que Funcionan [Families that
      work]>> program.. <<Familias que Funcionan>>[Families that work] is a family
      based drug-use prevention program resulting from the adaptation to the Spanish
      context of the prestigious North-American <<Strengthening Families Program 10
      14>>. The program was applied at four secondary schools (N = 380 pupils) in
      Asturias (northern Spain). This article presents the results of the assessment of
      this application after a two-year follow-up, regarding its effectiveness in the
      reduction of drug use among adolescents and its effects on certain family risk
      factors. Consistent attendance in the <<Familias que Funcionan>> program proved
      effective for reducing both rates (t= -2.73, p<.05 and t= -4.58, p<.005, for the
      1- and 2-year follow-ups, respectively) of increase in adolescent drug use and
      some family risk factors.

PMID- 19178856
TI  - [Emotional response to threatening stimuli in psychosis and anxiety disorders].
AB  - Emotional response to threatening stimuli in psychosis and anxiety disorders.
      Evolution has provided humans with an alarm system that may facilitate
      adaptation. Both psychosis and anxiety disorders involve danger detection
      difficulties. Our main goal is to compare threat responses of these diagnostic
      groups and with those of healthy subjects. We studied 24 subjects with an anxiety
      disorder diagnosis, 39 with psychosis, and 39 healthy control subjects. We
      compared threat and pleasantness perception using visual stimuli (human and
      nonhuman stimuli, either threatening or nonthreatening). Regarding threat
      perception, significant differences were found between psychosis and control
      groups. Subjects with anxiety disorder diagnosis evaluated any kind of stimuli
      more negatively. These results suggest differential emotional processing of
      diverse visual stimuli in these diagnostic groups.

PMID- 19178857
TI  - [Androgen levels, parenting styles and aggressive behavior in 5-6-year-old boys
      and girls].
AB  - Androgen levels, parenting styles and aggressive behavior in 5-6-year-old boys
      and girls. This study explores the relationship between androgen levels,
      parenting styles, and physical, verbal, and indirect aggression measures in 5-6
      year-old children. 129 children (60 boys and 69 girls) were assessed in relation
      to their aggression levels using a peer-rating technique. Parents completed the
      Parenting Styles and Dimensions Questionnaire, from which the different parenting
      styles were obtained. Testosterone, androstenedione and dehydroepiandrosterone
      (DHEA) were measured using an enzymoimmunoassay technique in saliva samples. A
      regression analysis indicated that the directive mother-androstenedione
      interaction at the age of 5 was predictive of physical aggression at the age of
      6. In specific terms, the results showed that, in boys with high androstenedione
      levels, directive maternal behavior is associated with physical aggression. The
      results are subsequently discussed in light of postulates related to parenting
      characteristic of developmental psychology and we suggest a potential link of our
      results with the hypothesis of maternal dominance.

PMID- 19178858
TI  - [Mathematical abilities and executive function in children with attention deficit
      hyperactivity disorder and learning disabilities in mathematics].
AB  - Mathematical abilities and executive function in children with attention deficit
      hyperactivity disorder and learning disabilities in mathematics. Even though 26%
      of children with attention deficit hyperactivity disorder (ADHD) show a specific
      mathematic learning difficulty (MLD), the studies have been scarce. The present
      study had the following goals: 1) to study the profile related to cognitive and
      metacognitive skills implied in calculation and problem-solving in children with
      ADHD+MLD, and to compare them in children with ADHD, children with MLD, and
      children without problems; 2) to study the severity of the deficit in executive
      function (EF) in children with ADHD+MLD. Comparing the groups MLD, ADHD,
      ADHD+MLD, and children without problems, the results highlighted that children
      with ADHD+MLD showed a cognitive and metacognitive deficit in mathematic
      achievement. Furthermore, results showed a more severe deficit in the EF in
      children with ADHD+MLD.

PMID- 19178859
TI  - [Comparative analysis of the efficacy of a playful-narrative program to teach
      mathematics at pre-school level].
AB  - Comparative analysis of the efficacy of a playful-narrative program to teach
      mathematics at pre-school level. In this paper, the effectiveness of a programme
      comprising several components that are meant to consolidate mathematical concepts
      and abilities at the pre-school level is analyzed. The instructional methodology
      of this programme is compared to other methodologies. One-hundred 5-6 year-old
      children made up the sample that was distributed in the following conditions: (1)
      traditional methodology; (2) methodology with perceptual and manipulative
      components, and (3) methodology with language and playful components.
      Mathematical competence was assessed with the Mathematical Criterial Pre-school
      Test and the subtest of quantitative-numeric concepts of BADyG. Participants were
      evaluated before and after the academic course during which they followed one of
      these methodologies. The results show that the programme with language and
      playful components is more effective than the traditional methodology (p<.000)
      and also more effective than the perceptual and manipulative methodology
      (p<.000). Implications of the results for instructional practices are analyzed.

PMID- 19178860
TI  - The role of metacognitive experiences in the learning process.
AB  - Metacognition in the form of metacognitive knowledge (MK) -in this case, beliefs
      about learning-provides a database from which the learner can select strategies
      for the regulation of learning. However, strategic regulation presupposes that
      the learner is aware that learning is not progressing well, or fluently, or has
      failed. This awareness takes the form of metacognitive experiences (ME), that is,
      feelings, estimates, or judgments related to the features of the learning task,
      of the cognitive processing as it takes place, or of its outcome. The critical
      feature of ME is their affective character which gives them access both to the
      cognitive and the affective regulatory loop of behavior. Being part of the
      affective loop, ME are related to motivation and self-processes; being part of
      the cognitive loop, they are connected to MK and to metacognitive skills, the
      latter being declarative and procedural knowledge. Thus, ME offer awareness that
      links the present with the past learning experiences and facilitates or inhibits
      self-regulation of learning in the present as well as in the future.

PMID- 19178861
TI  - [School bullying and violence in the Autonomous Community of the Basque Country].
AB  - School bullying and violence in the Autonomous Community of the Basque Country.
      This study explores some characteristics of school bullying in the Autonomous
      Community of the Basque Country, using descriptive methodology. The sample
      comprises 5,983 participants from ages 10 to 16 years, distributed in 169
      schools, to whom the Defensor del Pueblo School Violence Questionnaire was
      administered. The results reveal that: 1) the great majority of the students feel
      well treated by their teachers and a percentage of teachers (5.3%-12.2%) are
      mistreated by the students; 2) between 3% and 4.5% of the students are quite
      often afraid to go to school; 3) most of the victims from Primary Education talk
      about their problems with their families and those from Secondary Education, with
      their friends; 4) witnesses intervene to stop a bullying situation when the
      victim is their friend, and the aggressors perceive that many classmates
      encourage them, help them, or do not do anything; and 5) some Primary students
      think that the teachers punish the aggressors, whereas in Secondary Education,
      they perceive that the teachers are inhibited by this situation. The results
      suggest the need for strategies to identify school bullying and for
      psychoeducational intervention.

PMID- 19178862
TI  - [Factors that influence the prognosis for recovery in psychosocial risk families:
      the role of child resilience].
AB  - Factors that influence the prognosis for recovery in psychosocial risk families:
      The role of child resilience. This study analyses the indicators, such as child
      resilience, that influence prognosis for recovery in psychosocial risk families,
      by examining the combination that better discriminates between a favourable
      prognosis and an unfavourable one. For this purpose, the evaluation of the
      prognosis of 418 cases of children and their families (224 two-parents and 194
      one-parent) were examined through the Psychosocial Risk Profile of the Family,
      which was filled in by professionals from social services. The impact level on
      development, the temporality of the problem, and parents' attitudes about the
      intervention, their children and the service affected the prognosis of both
      families. Child resilience selectively influenced the favourable prognosis in two
      parent families whereas the risk level affected the unfavourable prognosis in one
      parent families. Child resilience was only related to those risk indicators which
      reflect more continuity of the problem and an accumulation of negative life
      events, but also to some compensatory factors such as the parents' expectations
      of the child's future that reflect parental competence.

PMID- 19178863
TI  - Group cohesion: Relationships with work team culture.
AB  - The aim of this study was to examine the relationships between group cohesion and
      the perceived culture and desired culture of work teams. Two separate studies
      were carried out with a time interval of one year. The first study had a sample
      of 50 work teams belonging to different organizations and the second study had a
      sample of 75 work teams. We used Lindell's index of agreement to estimate the
      culture and cohesion variables. Multiple and hierarchical regression analysis in
      both studies confirmed our initial hypothesis, showing that perceived and desired
      culture were positively related to group cohesion, and that culture gap had a
      negative association with cohesion. To a lesser extent, control variables such as
      job tenure and gender had a positive relationship with cohesion. The implications
      of these results are discussed along with the importance of considering the group
      level as analysis.

PMID- 19178864
TI  - [Work modulation: worker's adaptation strategies to regulate task and person
      demands].
AB  - Work modulation: Worker's adaptation strategies to regulate task and person
      demands. This research addresses the possible work modulation by the worker.
      Modulation is understood as an active coping mechanism, and it includes diverse
      strategies aimed at regulating work demands, guided by subjective matching
      criteria. Participants were 719 workers from several jobs that completed a
      questionnaire about their work task and person contents, using a cross-sectional
      design. In general terms, results support that work modulation tends to be
      specialized, depends on thresholds, and it is guided by an internal criterion. It
      is concluded that workers do turn to this mechanism to adapt to their work, whose
      strategies can be trained with a view to maintaining their employee well-being
      and preventing health risks at work.

PMID- 19178865
TI  - [Volunteer satisfaction: Internal structure and relationship with permanence in
      organizations].
AB  - Volunteer satisfaction: Internal structure and relationship with permanence in
      organizations. The concept of satisfaction is considered theoretically relevant
      in practically all the studies that have investigated the factors that influence
      the permanence of volunteer participation in organizations. However, the
      practical results are not conclusive, perhaps due to the wide range of ways in
      which the concept is understood and measured. The object of this study is: to
      analyse the internal structure of satisfaction and to verify its relationship
      with volunteer duration in organizations. The results of the factor analysis
      yield a three-factor structure: Satisfaction with the management of the
      organization, Satisfaction with the tasks, Satisfaction of motivations. The three
      factors allow us to differentiate between individuals who remain in the
      organization for a period of 12 consecutive months, and those who leave earlier.
      The results of structural equation model analysis show that the relationship
      between satisfaction and the length of time that volunteers stay with the
      organization is affected by the intention to remain.

PMID- 19178866
TI  - [Validation of the Questionnaire of Emotional Maladjustment and Adaptive
      Resources in Infertility (DERA)].
AB  - Validation of the Questionnaire of Emotional Maladjustment and Adaptive Resources
      in Infertility (DERA). Given the absence of measures to help psychologists
      working with infertile couples, this paper presents the process of developing a
      standardized measure to assess emotional maladjustment and adaptive resources in
      this population. A cross-sectional design was utilized to gather data from the
      assisted reproduction units of two public hospitals. Preliminary analyses were
      performed with a sample of 85 infertile patients. Psychometric properties of the
      measure were tested with a second sample of 490 infertile patients. Concerning
      reliability analyses, alpha indexes were adequate both for the measure and its
      factors. Concerning validity, second-order factor analysis yielded a four-factor
      solution that conjointly explains 56% of the total variance. Additional analyses
      with a third sample of 50 participants from the general population matched with a
      sample of 50 infertile participants were performed. In sum, this measure seems to
      be a useful psychological assessment tool to determine emotional adjustment, and
      individual, and interpersonal resources, for coping with infertility diagnosis
      and treatment.

PMID- 19178867
TI  - [Sex differences in criteria and standards of scientific and teaching
      productivity of Spanish teaching staff].
AB  - Sex differences in criteria and standards of scientific and teaching productivity
      of Spanish teaching staff. The aim of this study is to analyze differences in
      university teachers' opinion about the criteria and standards of scientific and
      teaching productivity, as well as the minimum number of criteria to be accredited
      as an Associate Professor or Professor. For this purpose, two representative
      samples of Spanish university teachers (97% interval confidence and 3% estimation
      error) were polled. These samples were made up of 960 male and 329 female
      university teachers. Results show that there are important gender differences.
      Females show a higher level of demand to achieve accreditation than do males.
      Thus, females are more demanding in more than 43% of the criteria to be
      accredited as an Associate Professor and in 54% of the criteria to be accredited
      as a Professor, compared to males. On the contrary, males only score higher than
      females in one of the criteria (articles published in the Journal Citation
      Reports).

PMID- 19178868
TI  - [Convergent validity of two tests of conscientiousness].
AB  - Convergent validity of two tests of conscientiousness. The absence of
      correspondence between objective measurement of behavior and measurement based on
      self-report along with generalized use of questionnaires as personality
      assessment instruments raises a problem with regard to the validity of assessment
      instruments in this area of study. The goal of this work is to obtain a
      convergent validity measure for an objective assessment computerized task of
      conscientiousness based on the development of a functional equally but
      morphologically different task. The features of the designed assessment task are
      commented upon. The sample was made up of 267 university graduates (194 males and
      73 females). The high convergent validity value obtained (r= .638, p<.001) is a
      first step in the validation process of both tasks.

PMID- 19178869
TI  - Calculating the main alternatives to null-hypothesis-significance testing in
      between-subject experimental designs.
AB  - The present article deals with the controversy about null hypothesis significance
      testing (NHST) that currently exists in psychological research. The main
      criticisms and counter-criticisms posed by its detractors and supporters are
      presented. Alternatives have been proposed to replace or complement the NHST, as
      recommended by the Task Force on Statistical Inference of the APA, and these are
      explained. Furthermore, the procedure for calculating these alternatives using
      SPSS statistical software in a two-way between-factor design is demonstrated.
      Thus, an attempt is made to provide the applied researcher with resources that
      make it possible to analyse and interpret the results of any research study using
      a group of indicators that lends a high level of validity to the statistical
      inference performed.

PMID- 19178870
TI  - [An aligned rank test for a nonparametric analysis of the two-way interaction].
AB  - An aligned rank test for a nonparametric analysis of the two way interaction.
      Research problems that require nonparametric analysis of the interaction
      frequently arise in the behavioral sciences. There is, however, a lack of
      available procedures in commonly used statistical packages such as SAS or SPSS.
      The purpose of the present study is to review the fundamentals of the aligned
      rank test for two widely used two-way research designs in psychology. The
      procedure has shown good properties in nonnormal distributions in terms of Type I
      Error control and statistical power. It is easily conducted using common
      statistical packages. It is applied to two case studies which result in gender
      differences in linguistic abilities in blind children not revealed by other
      procedures. Limitations of the aligned rank test have been observed in situations
      of covariance heterogeneity across groups, and also with sample sizes smaller
      than ten participants per condition. Its adequate use after model diagnostics
      can, however, increase sensitivity to detect behavioral effects of theoretical or
      practical interest.

PMID- 19178871
TI  - [Development of the proactive/reactive aggressiveness questionnaire for teachers:
      factor structure and psychometric properties].
AB  - Development of the proactive/reactive questionnaire for teachers: factor
      structure and psychometric properties. The main purpose of this study was to
      develop a proactive/reactive aggression questionnaire for children in Spanish,
      reported by teachers. To develop the questionnaire, we selected eight items from
      the most widely used questionnaires in English using the criteria of a group of
      experts. Exploratory factor analysis on a sample of 267 children yielded two
      dimensions, one of proactive and the other of reactive aggression, consisting of
      four items each. Both scales showed good reliability and were related to an
      external criterion such as academic performance.

PMID- 19178872
TI  - [CONS-32: factor structure and psychometric properties].
AB  - CONS-32: Factor structure and psychometric properties. Risk prevention in the
      construction industry has a psychosocial etiology. This article studies the
      psychometric properties of a scale (CONS-32) created to detect personal
      prevention and job-related risks. The 336 participants in the present study are
      from the construction industry and reside in Catalonia. After exploratory factor
      analysis of the scale, the structure is shown to consist of four factors that
      involve job characteristics and individual behaviours. The results indicate
      adequate reliability. Therefore, the present scale may be ideal for identifying
      safety risks in the construction industry.

PMID- 19178873
TI  - Terazosin treatment suppresses basic fibroblast growth factor expression in the
      rat ventral prostate.
AB  - PURPOSE: Alpha1-adrenergic receptor antagonists may not act solely on smooth
      muscle contractility. We evaluated the in vivo effect of the alpha1 blocker,
      terazosin, on the expression of basic fibroblast growth factor (bFGF) in the rat
      ventral prostate. METHODS: Wistar rats were treated with terazosin (1.2 mg/kg
      body weight, po, every second day) for 120 days. The expression of bFGF was
      assessed immuno-histochemically in tissue sections and by Western blotting in
      whole tissue preparations. RESULTS: Terazosin treatment did not affect prostate
      weight or histomorphology. In the control group, epithelial and stromal cells
      demonstrated positive staining for the anti-bFGF antibody. In contrast, the same
      staining in terazosin-treated specimens was either absent or extremely weak. An
      analogous difference was observed among the corresponding immunoblots.
      CONCLUSIONS: These findings implicate the reduction of bFGF expression by
      terazosin as a potential additional molecular mechanism of its action that may
      include alterations in peptide growth factor mediated prostate homeostasis.

PMID- 19178874
TI  - Comparison of pharmacokinetics of L-carnitine, acetyl-L-carnitine and propionyl-L
      carnitine after single oral administration of L-carnitine in healthy volunteers.
AB  - PURPOSE: To investigate the pharmacokinetics of L-carnitine (LC) and its
      analogues, acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) in healthy
      volunteers after single L-carnitine administration. METHODS: Liquid L-carnitine
      (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma
      and urine concentrations of L-carnitine, ALC and PLC were detected by HPLC.
      RESULTS: The maximum plasma concentration (Cmax) and area under the curve (AUC 0
      infinity) of L-carnitine was 84.7+/-25.2 micromol x L(-1) x h and 2676.4+/-708.3
      micromol x L(-1) x h, respectively. The elimination half-life of L-carnitine and
      the time required to reach the Cmax (Tmax) was 60.3+/-15.0 and 3.4+/-0.46 h,
      respectively. The Cmax of ALC (12.9+/-5.5 micromol x L(-1)) and PLC (5.08+/-3.08
      micromol x L(-1)) was lower than L-carnitine (P < 0.01), so as the AUC 0-infinity
      (166.2+/-77.4 and 155.6+/-264.2 micromol x L(-1) x h, respectively, P < 0.01).
      The half-life of ALC (35.9+/-28.9h) and PLC (25.7+/-30.3 h) was also shorter than
      L-carnitine (P < 0.01). The 24h accumulated urinary excretion of L-carnitine, ALC
      and PLC were 613.5+/-161.7, 368.3+/-134.8 and 61.3+/-37.8 micromol, respectively.
      CONCLUSION: L-carnitine has a greater maximum plasma concentration than ALC and
      PLC. L-carnitine also has a longer half-life than ALC and PLC. These data may
      have important implications in the designing of dosing regimens for L-carnitine
      or its analogues, such as ALC or PLC.

PMID- 19178875
TI  - Serum IgA1 from patients with IgA nephropathy up-regulates integrin-linked kinase
      synthesis and inhibits adhesive capacity in podocytes through indirect pathways.
AB  - PURPOSE: To investigate the influence of IgA1 isolated from IgA nephropathy
      (IgAN) patients on integrin-linked kinase (ILK) synthesis and adhesive capacity
      of podocytes through indirect pathways. METHODS: IgA1 was isolated from healthy
      control or IgAN patients' sera using jacalin affinity chromatography and S-200
      chromatography. Podocytes were treated with medium from mesangial cells incubated
      with aggregated IgA1 (aIgA1, 100 microg/ml), in the presence or absence of
      valsartan (10(-5)M) or neutralizing antibodies of tumor necrosis factor-alpha
      (TNF-alpha, 50 ng/ml). Adhesive capacity of podocytes was assessed by cell
      counting manually and hexosaminidase assay. Real-time PCR and western blotting
      were used to detect the expression of ILK. RESULTS: Medium from mesangial cells
      incubated with aIgA1 from IgAN patients reduced podocyte adhesion to collagen
      compared with medium from mesangial cells incubated with control medium(RPMI-1640
      with 0.5% FBS) (35.0+/-4.8% vs. 60.0+/-2.0%; P < 0.05). While medium from
      mesangial cells incubated with aIgA1 from IgAN patients upregulated ILK
      expression in podocytes at mRNA and protein levels compared with medium from
      mesangial cells without aIgA1 incubated (1.6-fold and 1.38-fold higher than
      control, respectively, P < 0.05). Defects in podocyte adhesion and up-regulation
      of ILK synthesis induced by medium from mesangial cells incubated with aIgA1 from
      IgAN patients can be partially reversed by the pre-treatment for 1 hour with
      valsartan(P < 0.05), while pre-treatment with neutralizing antibodies of TNF
      alpha produced no protective effect on podocytes (P > 0.05). CONCLUSION: Serum
      IgA1 from IgAN patients may inhibit adhesive capacity and up-regulate ILK
      synthesis in podocytes through indirect pathways.

PMID- 19178876
TI  - Connecting KCNQ1 mutants with clinical outcome.
AB  - PURPOSE: Mutations in KCNQ1 are linked to long QT and other syndromes. This study
      reports a method to predict clinical outcome when a mutation at KCNQ1 is found.
      METHODS: We used amino-acid distribution probability to measure KCNQ1 mutants,
      and cross-impact analysis to couple KCNQ1 mutants with clinical outcome. Then,
      Bayesian equation was used to calculate the probability of occurrence of long-QT
      syndrome in the presence of a mutation. RESULTS: Seventy-six mutations were
      classified into two groups according to whether a mutation increased or decreased
      amino-acid distribution probability. Cross-impact analysis showed that a mutation
      that increases the distribution probability has a greater chance of causing long
      QT syndrome than a mutation that decreases the distribution probability. Bayesian
      calculation suggested that a patient would have a 90% chance of developing long
      QT syndrome when a mutation is found at KCNQ1. CONCLUSION: This study details the
      process of building a quantitative relationship between KCNQ1 mutations and
      clinical outcome and provides the probability of LQT1 in the presence of a
      mutation.

PMID- 19178877
TI  - Inability of healthy subjects to deposit potassium during hypokinesia and
      potassium supplementation.
AB  - OBJECTIVE: To determine the effect of potassium (K+) supplementation and
      hypokinesia (HK; diminished movement) on muscle K+ content and K+ loss. METHODS:
      Studies were conducted on 40 healthy male volunteers during a pre-experimental
      period of 30 days and an experimental-period of 364 days. Volunteers were equally
      divided into four groups: unsupplemented control subjects (UCS), unsupplemented
      experimental subjects (UES), supplemented control subjects (SCS), and
      supplemented experimental subjects (SES). A daily supplement of 1.17 mmol
      potassium-chloride (KCl) per kg body weight was given to the subjects in the SCS
      and SES groups. RESULTS: Muscle K+ content decreased (P < 0.05), and plasma K+
      concentration, and K+ loss in urine and feces increased (P < 0.05) in the SES and
      UES groups compared with their pre-experimental levels and the values in their
      respective control groups (SCS and UCS). Muscle K+ content decreased more (P <
      0.05), and plasma K+ concentration and K+ loss in urine and feces increased more
      (P < 0.05) in the SES group than in the UES group. CONCLUSION: Muscle K+ content
      is not decreased by the K+ deficient diet and K+ loss is not increased by the
      higher muscle K+ content in the body. Rather it is caused by the inability of the
      body to use K+ during HK and K+ supplementation.

PMID- 19178878
TI  - Seroprevalence of Toxoplasma gondii, rubella and cytomegalovirus among pregnant
      women in western region of Turkey.
AB  - PURPOSE: Prenatal screening for antibodies to Toxoplasma gondii (T. gondii),
      rubella virus and cytomegalovirus (CMV) infectious agents is an important tool in
      this process. The aim of this study was to determine the seroprevalence of these
      infections through antenatal screening in Kocaeli region. MATERIAL AND METHODS:
      1972 samples of sera were tested for antibodies to TORCH agents known to cause
      serious congenital infections: T. gondii, rubella, CMV. Anti-Toxoplasma, anti
      rubella and anti-CMV IgM and IgG antibodies were assayed by ELISA method using
      Abbott kits (Axsym, Abbott, USA) according to the manufacturer's instructions.
      RESULTS: Of 1972 pregnant women, seropositivity for anti-toxoplasma IgG antibody
      was found in 952 (48.3%), while 8 (0.4%) of the subjects tested were positive for
      the anti-Toxoplasma IgM antibody only, and 31 (1.6%) of the subjects tested were
      positive for anti-Toxoplasma IgG+IgM antibodies together. The seropositivities
      for anti-rubella IgG, IgM and IgG+IgM together were found in 1896 (96.1%), 4
      (0.2%) and 35 (1.8%) of the pregnant women, respectively. The seropositivities
      for anti-CMV IgG, IgM and IgG+IgM together were found in 1900 (96.4%), 13 (0.7%)
      and 37 (1.9%) of the pregnant women, respectively. CONCLUSION: Widespread
      population screening may contribute to the prevention of congenital infections
      due to TORCH agents. Because of the high seropositivity of T. gondii, rubella and
      CMV in pregnant women, preventive measures should be taken.

PMID- 19178879
TI  - Haemodialysis through a cellulose membrane induces dephosphorylation of CD11b and
      promotes leukocyte adhesion to endothelial cells.
AB  - PURPOSE: To explore modifications in signal mechanisms involving CD11b and
      leukocyte adhesion in patients under haemodialysis (HD). METHODS: Samples were
      obtained from uremic patients at baseline, 15 and 120 min of HD from both
      arterial and venous lines. CD11b expression was studied by flow cytometry. To
      study signalling mechanisms, CD11b was immunoprecipitated using a specific
      antibody. Immunoprecipitates were resolved by 8% SDS-PAGE to measure
      phosphorylation in immunoblots. Leukocyte adhesion was measured after blood
      perfusion using endothelial cells (EC) as adhesive substrate. Parallel studies
      were performed with blood from healthy donors. RESULTS: The percentage of CD11b+
      cells increased during HD with a cellulose membrane in the venous line at 15 and
      120 min (6.2+/-2.9% and 11.0+/-7.1%) and in the arterial line at 120 min (11.5+/
      8.5 vs. 3.1+/-1.0% in control P < 0.05). After 120 min HD, CD11b phosphorylation
      decreased in leukocytes from both arterial (72.6+/-2.9) and venous lines (51.8+/
      6.5) vs. basal samples (119.5+/-15.5 P < 0.005). Control leukocytes showed
      enhanced adhesion to uremic EC compared with control EC (3.0+/-0.3 vs. 2.3+/-1.0
      leukocytes x100 EC(-1) P < 0.05). Uremic leukocyte adhesion was enhanced after HD
      compared with basal samples 4.2+/-0.2 leukocytes/100 EC in the arterial and 4.4+/
      0.3 in the venous line; after 120 min vs 2.3+/-1.0 (P < 0.005). CONCLUSION:
      Leukocyte activation during HD through a cellulose membrane occurs with decreases
      in CD11b phosphorylation. Activation also induces increases in CD11b expression
      associated with enhanced leukocyte adhesion to uremic endothelial cells.

PMID- 19178880
TI  - Methicillin-resistant S. aureus colonization in Mexican children attending day
      care centres.
AB  - PURPOSE: To determine MRSA carriage rates and genetic relationships of S. aureus
      strains in children attending day care centres in 14 cities from three geographic
      regions in Mexico. MATERIALS AND METHODS: Cross-Sectional Study performed in
      apparently healthy children aged from 6 mo to 6 yr attending day care centres
      (DCCs). From September 2002 To January 2003, 2345 nasopharyngeal specimens from a
      similar number of children were collected. Nasopharyngeal samples for bacterial
      isolation were obtained by standard methods. Antimicrobial susceptibility was
      determined and genetic relatedness of all MRSA isolates was determined by pulsed
      field gel electrophoresis (PFGE). RESULTS: S. aureus was identified in 237
      children (10.1%), twenty-two children had MSRA for an overall prevalence of MRSA
      carriage of 0.93%. Children attending DCCs from cities located in the north and
      south of Mexico showed higher prevalence than children from DCCs in the central
      region; 1.75%, and 1.71 vs. 0.08%, respectively (P < 0.05). PFGE demonstrated six
      different restriction profiles of MRSA with a predominant pattern. CONCLUSIONS:
      We documented the presence of MRSA strain colonizing children attending DCCs in
      Mexico, mainly in the south and north regions of the country. Clone A and B which
      are closely related represented 45 % of the total of MRSA isolates. We found
      both, SCCmec type II and type IV strains in the three regions.

PMID- 19178881
TI  - Comparison of mechanical motion profiles following instrumented fusion and non
      instrumented fusion at the L4-5 segment.
AB  - PURPOSE: To investigate the difference in motion profiles between instrumented
      and non-instrumented fusion of the lumbar spine. METHOD: In vivo retrospective
      radiological analysis of dynamic (flexion-extension) lateral plain films was
      performed in different lumbar spine fusion types. Twenty-eight patients underwent
      lumbar fusion surgery at the L4/5 level. Fourteen patients underwent anterior
      fusion surgery without implantation, and the others underwent posterior
      instrumented fusion. Segmental angular motion was measured at the fused and
      adjacent levels using dynamic plain lateral film 2 years after operation.
      RESULTS: The anterior uninstrumented fusion group showed mean 2.0 degrees of
      segmental angular motion at the fused level compared with mean of 0.8 degrees in
      the posterior instrumented fusion group (P < 0.05). In contrast, at the proximal
      adjacent level, decreased angular motion (mean 7.7 degrees ) was noted in the
      anterior uninstrumented fusion group compared with mean 11.6 degrees in the
      posterior instrumented fusion group (P < 0.05). CONCLUSION: This study suggests
      that differing stiffness of fusion segments could cause different mechanical
      motion profiles at adjacent segments.

PMID- 19178882
TI  - Pulmonary cryptococcosis in non-AIDS patients.
AB  - PURPOSE: To clarify the clinical features and imaging characteristics of non-AIDS
      patients with pulmonary cryptococcosis. METHODS: We retrospectively collected 15
      HIV-negative patients with pathology-proved pulmonary cryptococcosis from Sep
      1992 to Jan 2008. Their medical records and radiological data were reviewed and
      analyzed. RESULTS: Only one patient was asymptomatic.Thirteen patients were
      immunocompetent and two were immunosuppressed. Three patients had associated
      cryptococcosis meningitis. The most common radiographic abnormalities were
      multiple pulmonary nodules or masses, seen in 8 and 5 cases of patients
      respectively. 14 patients received specific therapy for Cryptococcus neoformans.
      Two patients died. In the 11 patients with isolated pulmonary cryptococcosis,
      treatment consisted of fluconazole alone (n=7), in combination with amphotericin
      B (n=2), and both 5-flucytosine and amphotericin B (n=2). For the other 2
      patients with cryptococcosis meningitis, one was treated with amphotericin B
      alone and the other with fluconazole combined with amphotericin B and 5
      flucytosine. CONCLUSIONS: Non-AIDS patients might also susceptible to
      cryptococcosis infection. Histological examination is the principal method of
      diagnosis. The most common CT findings are solitary or multiple nodules with or
      without cavitation in the subpleural areas of the lung.

PMID- 19178883
TI  - Thyroid arterial embolization for the treatment of hyperthyroidism in a patient
      with thyrotoxic crisis.
AB  - PURPOSE: We report a case of hyperthyroidism in a young woman caused by Graves'
      disease that was successfully treated with thyroid arterial embolization.
      CLINICAL DETAILS: A 35 year-old woman with a history of thyrotoxic crises was
      admitted after the last thyroid crisis. Thyroid arterial embolization was used to
      treat the hyperthyroidism after it had been controlled. Immediately after
      embolization, the enlarged thyroid gland shrank and vascular murmurs disappeared.
      Serum thyroid hormones increased on day 3 following embolization but decreased
      gradually. Thyroid hormone returned to normal 2 months after embolization and
      remained normal at three years. CONCLUSION: Thyroid arterial embolization is an
      effective means to treat refractory hyperthyroidism.

PMID- 19178884
TI  - Telomerase activity (TMA) in tumour and peritumoural tissues in a rat liver
      cancer model.
AB  - PURPOSE: To study the levels of telomerase activity (TMA) in tumour and
      peritumoural tissues in a liver cancer model in rats, and to study the change in
      TMA expression over time. METHODS: Using the telomeric repeated amplification
      protocol (TRAP), TMA was measured in tumour tissue, peritumoural tissue and
      normal liver tissue of Walker-256 tumour-bearing rats at 4, 6 and 8 days after
      tumour implantation. RESULTS: TMA at day 4, 6 and 8 was 0.767+/-0.117, 0.768+/
      0.118 and 0.774+/-0.111 in tumour tissue, 0.389+/-0.263, 0.492+/-0.253 and
      0.584+/-0.239 in peritumoural tissue, and 0.231+/-0.022, 0.229+/-0.022 and
      0.233+/-0.021 in normal liver tissue, respectively. TMA in tumour tissue was
      higher than that in peri-tumour and normal liver tissues at all time points of
      measurement (P < 0.05). The TMA levels in tumour tissue and normal liver tissue
      did not show any change over time. TMA level in the peritumoural tissue increased
      with time; TMA level in animals sacrificed at day 8 was higher than that seen in
      animals sacrificed at day 4 (P < 0.05). CONCLUSION: TMA in walker-256 tumour
      bearing rats was higher than that in normal and peritumoural tissues. TMA level
      in the peritumoural tissue increased with time suggesting that TMA activation in
      peritumoural tissue may be an important factor promoting tumour growth.

PMID- 19178885
TI  - Attenuated vaccines for animal diseases.

PMID- 19178886
TI  - Control of tropical theileriosis with attenuated schizont vaccine in China.
AB  - Tropical theileriosis, a tick borne disease of cattle caused by the protozoan
      Theileria annulata, was widely distributed in northern China causing great
      economical losses before the 1980's. In the 1960's blood passaging, irradiation
      and in vitro culture of parasite were used for the development of attenuated
      vaccine. Two lines of the schizont stage were obtained which both provided
      sufficient protection against tick infestation or blood challenge in experimental
      and field trials. A gelatin protection technique allowed storage at 4 degrees C,
      significantly prolonged shelf life and permitted transport without a cold chain.
      The vaccines were commercialized and widely administered in epidemic areas,
      leading to control of T. annulata infection in China.

PMID- 19178887
TI  - Vaccination of cattle against tropical theileriosis in Uzbekistan using
      autochthonous live vaccine.
AB  - In Uzbekistan, 1984 cattle were vaccinated with the TAU-219 autochthonous live
      Theileria annulata vaccine under field conditions. There were no post-vaccination
      reactions recorded in calves vaccinated with 10 times the recommended dose, under
      semi-field conditions. After vaccination 53.9% of the vaccinates developed fever
      over 39.5 degrees C that lasted for a few days, but none developed clinical
      theileriosis or required drug treatment during the 3-week follow-up. The numbers
      of animals in which piroplasms were detected before and after vaccination were
      similar (7.15% and 7.25%, respectively), indicating previous exposure to T.
      annulata tick infection. Following vaccination none of the 241 pregnant cows
      aborted. Milk production during 30-45 days was similar in non-vaccinated and
      vaccinated cows, at about 5.2-5.9L/day. During 1999-2006 a total of 11,000 field
      grazing cattle were safely vaccinated in Uzbekistan.

PMID- 19178888
TI  - Influence of subculturing on gene expression in a Theileria lestoquardi-infected
      cell line.
AB  - In this study potential molecular markers for identification of attenuation in a
      Theileria lestoquardi-infected cell line to be used in vaccination trials were
      identified. Two markers associated with attenuation in Theileria annulata vaccine
      strains were analyzed (metalloproteinase activity and TNF? mRNA expression). The
      result showed a decreased activity of MMP 9 and decreased mRNA expression of TNF?
      with increasing passage number. Suppression subtractive hybridization was used to
      identify potential new markers of attenuation. Random screening revealed nine
      differentially expressed genes, one from the parasite and eight from the host.
      Quantitative real time-PCR confirmed mRNA expression of the parasite vacuolar
      H+ATPase to be downregulated at higher passages.

PMID- 19178889
TI  - Tropical theileriosis: cytotoxic T lymphocyte response to vaccination.
AB  - Cattle which survive an infection with Theileria annulata become effectively
      immune to challenge with the same parasite strain, and are thought to be
      protected against a heterologous strain of the parasite. T-cells play a crucial
      role in both induction and maintenance of immunity to T. annulata. The generation
      of cytotoxic T lymphocytes (CTL) is closely related to the control of the
      infection - macroschizont-infected cells are killed in an MHC class I restricted
      manner. Any strain-specificity induced by immunisation is likely to be manifested
      by CTL. Besides CTLs, CD4+ T-cells also play an important role in protective
      immunity to T. annulata infection.

PMID- 19178890
TI  - Vaccination of cattle against B. bovis infection with live attenuated parasites
      and non-viable immunogens.
AB  - Susceptible dairy cattle were immunized with attenuated, live calf-derived, in
      vitro-cultured or biologically cloned Babesia bovis, with non-viable exoantigens,
      or with recombinant rhoptry-associated protein 1 (rRAP1). Antibody response
      assessed by the indirect fluorescent assay (IFA) and by the growth inhibition
      activity in vitro showed that seroconversion correlated with neutralization
      activity in vitro in all immunized groups, but not with protective immunity in
      vivo. The protective responses elicited by immunization with completely avirulent
      biologically cloned live parasites, or by the exoantigens were sufficient for
      highly susceptible dairy cattle, in which prime immunization with blood-derived
      attenuated parasites cause clinical babesiosis. Upon challenge with virulent live
      parasites all immunized calves were solidly protected, but only partial
      protective immunity was acquired by rRAP1 immunization.

PMID- 19178891
TI  - Experimental use of the attenuated Ehrlichia ruminantium (Welgevonden) vaccine in
      Merino sheep and Angora goats.
AB  - The attenuated Ehrlichia ruminantium (Welgevonden) stock provides protection
      against a virulent homologous needle challenge in Merino sheep and Boer goats
      against heartwater. In this study, cryopreserved stabilates were tested for their
      suitability as a vaccine in Merino sheep. Vaccination did not produce disease and
      upon challenge with the virulent homologous stock all animals were fully
      protected. The vaccination protected all except one animal out of 5 challenged 12
      months after immunization. The intramuscular route gave better protection than
      the subcutaneously applied vaccine. The attenuated vaccine was further evaluated
      in highly susceptible Angora goats. Although the attenuated vaccine showed an
      unexpectedly high degree of virulence, animals were fully protected against a
      lethal needle challenge.

PMID- 19178892
TI  - Review on the experience with live attenuated vaccines against tropical
      theileriosis in Tunisia: considerations for the present and implications for the
      future.
AB  - The choice of a vaccine candidate against tropical theileriosis was based on key
      epidemiological considerations inherent to the main target endemic situation in
      Tunisia. One of the attenuated cell lines was retained as a vaccine candidate on
      the basis of small-scale trials testing the intrinsic safety aspects of the
      vaccine for the targeted animal categories in the dominant endemic situation
      where it will be used. The vaccine efficacy was confirmed in pilot vaccination
      campaigns using fresh culture and thawed cryopreserved vaccine doses delivered to
      the field using a new delivery system not requiring a cold chain. The potential
      benefit of the live attenuated Tunisian vaccine was evaluated using simple
      economical models.

PMID- 19178893
TI  - Progress in development of vaccine against Hyalomma anatolicum anatolicum-Indian
      scenario.
AB  - Hyalomma anatolicum anatolicum, a three host tick vector transmitting the
      causative agent of bovine tropical theileriosis, is widely distributed throughout
      India. As a component of integrated control measures against the tick vector,
      attempts have been made to identify candidate protein molecules for development
      of an anti-tick vaccine in the different stages of this tick species. By
      strategic methods of isolation of the targeted molecules using affinity
      purification of proteins showing reactivity with immunoglobulins of animals
      previously immunized with different sources of tick antigen, six proteins were
      isolated in a significantly pure form. The recovery percentage of the candidate
      proteins was very low in the range of 1.8-8.0%. The protective potentiality of
      the antigens was tested in immunization and challenge trials and maximum
      potential was observed in the proteins isolated from total larval extracts,
      nymphal extracts and in larval glycoprotein. One of the antigens with a molecular
      weight of 37kDa isolated from larvae of H. a. anatolicum was found to have some
      adverse effect on development of Theileria annulata in the vector tick. The
      progress in the development of immunoprophylactic measures against H. a.
      anatolicum is discussed.

PMID- 19178895
TI  - Feeling of knowing for names in response to faces.
AB  - Participants were asked to recall the names when shown photographs of faces in
      both a semantic task (Experiment 1) and an episodic task (Experiments 2 and 3).
      When recall failed, feeling of knowing (FOK) ratings were solicited. In addition,
      participants reported on the strategies that they used to make their ratings,
      whether they could recall other pieces of information (the target-accessibility
      strategy, e.g., Koriat, A. (1993). How do we know that? The accessibility model
      of the feeling of knowing. Psychological Review, 100, 609-639) or whether the
      faces simply looked familiar (the cue-familiarity strategy, e.g., Schwartz, B.
      L., & Metcalfe, J. (1992). Cue familiarity but not target accessibility enhances
      feeling of knowing ratings. Journal of Experimental Psychology: Learning, Memory,
      and Cognition, 18, 1074-1083). In all experiments, FOK ratings were fairly
      accurate in that participants were successful in predicting their performance on
      a subsequent recognition test. More importantly, participants reported using the
      cue-familiarity strategy more often, although they gave higher FOK ratings when
      they reported using the target-accessibility strategy. The FOK ratings that were
      given using the two strategies were equally accurate.

PMID- 19178894
TI  - Protection of guinea pigs and swine by a recombinant adenovirus expressing O
      serotype of foot-and-mouth disease virus whole capsid and 3C protease.
AB  - Two recombinant adenoviruses were constructed expressing foot-and-mouth disease
      virus (FMDV) capsid and 3C/3CD proteins in replicative deficient human adenovirus
      type 5 vector. Guinea pigs vaccinated with 1-3 x 10(8)TCID(50) Ad-P12x3C
      recombinant adenovirus were completely protected against 10,000GID(50) homologous
      virulent FMDV challenge 25 days post vaccination (dpv). Ad-P12x3CD vaccinated
      guinea pigs were only partially protected. Swine were vaccinated once with
      1x10(9)TCID(50) Ad-P12x3C hybrid virus and challenged 28 days later. Three of
      four vaccinated swine were completely protected against 200 pig 50% infectious
      doses (ID(50)) of homologous FMDV challenge, and vaccinated pigs developed
      specific cellular and humoral immune responses. The immune effect of Ad-P12x3C in
      swine further indicated that the recombinant adenovirus was highly efficient in
      transferring the foreign gene. This approach may thus be a very hopeful tool for
      developing FMD live virus vector vaccine.

PMID- 19178896
TI  - Risk factors and outcome of early recurrence after resection of small
      hepatocellular carcinomas.
AB  - BACKGROUND: This study aimed to clarify risk factors for early recurrence and
      examine the subsequent outcome in patients undergoing potentially R0 resection of
      small hepatocellular carcinomas (HCCs) (<or=2 cm in greatest dimension). METHODS:
      Eighty-nine patients were divided into 2 groups as follows: 26 patients suffering
      from recurrence within 2 years of surgery (early recurrence group) and 63
      patients who were disease-free for at least 2 years (disease-free 2Y group).
      RESULTS: Only 7 of 63 patients (11%) from the group that was disease-free for at
      least 2 years died during the 5-year period after surgery, whereas 13 of 26
      patients (50%) from the early recurrence group died. Multivariate analysis showed
      that the preoperative maximum removal rate of technetium-99m-diethylenetriamine
      pentaacetic acid-galactosyl human serum albumin and microscopic vascular invasion
      were independent predictors of the early recurrence of small HCC. CONCLUSIONS:
      Early recurrence of small HCC is the leading cause of death within 5 years after
      R0 resection. The preoperative hepatic functional reserve influences early
      recurrence, even in patients with small tumors.

PMID- 19178897
TI  - Stage migration with sentinel node biopsy in breast cancer.
AB  - BACKGROUND: Axillary staging provides the single most important piece of
      prognostic information in breast cancer patients. This retrospective study was
      performed to document the phenomenon of stage migration. METHODS: Of 392
      patients, 5 (1%) failed identification of sentinel lymph nodes (SLNs) and
      therefore underwent axillary lymph node dissection (ALND). Four patients (80%)
      had metastatic lymph nodes, 302 (77%) patients had negative SLNs, 47 (15%)
      underwent ALND, 85 (22%) had positive SLNs, 11 (13%) received adjuvant radiation
      treatment to the axilla, and 74 (87%) underwent completion ALND. RESULTS: The
      median (quartiles) follow-up period was 29 months (19-46 mo). Twenty of 392 (5%)
      patients had disease relapse; 2 of which were local (.5%) and the rest were
      systemic. Earlier relapse was related significantly to lymph node status, tumor
      grade, and tumor size. SLN-negative patients who did not receive ALND had a
      relapse rate of 2.3% (6 of 256) compared with 0% in those who were truly negative
      based on confirmatory ALND. SLN-positive patients who did not receive ALND had a
      9% (1 of 11) relapse rate. DISCUSSION: The stage-matched pattern of relapse
      between SLN biopsy and ALND patients revealed lower relapse rates in SLN biopsy
      staged patients, documenting the stage migration phenomenon.

PMID- 19178898
TI  - Attrition of categoric general surgery residents: results of a 20-year audit.
AB  - BACKGROUND: Attrition of general surgery residents is of continued concern in
      graduate medical education. It results in loss of morale and resources and often
      leaves programs scrambling to find replacement residents. The aim of this study
      was to evaluate the incidence of attrition of categoric general surgery residents
      as well as the fate of those who left the general surgery training program among
      a defined cohort of categoric general surgery residents in a university hospital
      residency training program. METHODS: We retrospectively reviewed the files of all
      general surgery residents at the Yale University School of Medicine-Yale New
      Haven Hospital Surgery Program who began as categoric interns from July 1, 1986
      to June 30, 2006. Ninety-nine residents were identified. Attrition of residents
      was divided into withdrawals (changed specialty or left graduate medical
      education), transfers (transferred to a different program in general surgery),
      and dismissals (dismissed from the program). RESULTS: Among the 99 residents who
      began as categoric interns from 1986 to 2006, 66 of 99 (67%) were men. Thirty of
      99 (30%) failed to complete the general surgery training program. Of these, 21 of
      30 (70%) withdrew, 5 of 30 (17%) transferred, and 4 of 30 (13%) were dismissed.
      Attrition occurred before entering the third clinical year in 23 of 30 (77%). Two
      of 30 (7%) left graduate medical education. Thirteen of 21 (62%) who withdrew
      entered primary care or another nonsurgical specialty, whereas 7 of 21 (38%)
      matriculated into a surgical subspecialty. The attrition rate was 40% (12 of 30)
      since the academic year 2000. The overall annual attrition rate for the past 20
      years was 6.7%. COMMENTS: Attrition in our general surgery training remains low.
      Most who leave remain in graduate medical education and transfer to a different
      specialty. The overwhelming majority leave before beginning their third clinical
      year. Although our 6.7% annual attrition rate remains favorable (national
      attrition rate in general surgery 5.8%), we must continue to analyze the root
      causes and solutions.

PMID- 19178899
TI  - Venous air emboli and computed axial tomography power contrast injectors.
AB  - A 47-year-old female presented to our level 1 trauma center following a single
      vehicle rollover. The computed tomography power injector was not appropriately
      primed with contrast, resulting in a large venous air embolus.

PMID- 19178900
TI  - Ruptured gastroduodenal artery pseudoaneurysm as the initial presentation of
      chronic pancreatitis.
AB  - Gastroduodenal artery pseudoaneurysm is a rare but life threatening complication
      of pancreatitis. Diagnosis and management of it remain challenging. Surgical
      treatment was associated with a high mortality. Percutaneous transarterial
      embolization of bleeding artery has recently been advocated as a definitive
      therapy and can be attempted as the initial measure to control bleeding. We
      herein report a case of chronic pancreatitis presented with ruptured
      pseudoaneurysm of gastroduodenal artery which was successfully controlled with
      transarterial embolisation.

PMID- 19178901
TI  - Emergent embolization of the gastroduodenal artery in the treatment of upper
      gastrointestinal bleeding. The experience from a surgeon-initiated interventional
      program.
AB  - BACKGROUND: Intractable nonvariceal upper gastrointestinal bleeding (UGIB) is
      associated with significant morbidity and mortality. Endovascular therapy is an
      alternative to surgery for high-risk patients. MATERIALS AND METHODS: Review of
      prospectively collected data from patients who underwent emergent gastroduodenal
      artery embolization for UGIB. RESULTS: Eight patients (mean age 68.5 years) were
      identified. They all had significant comorbidities and were deemed to be at high
      risk for surgical intervention. Endoscopy was performed in 7 patients. Active
      extravasation was present at the time of embolization in 5 (62.5%) patients. The
      technical success and clinical response rates were each 100%. The 30-day
      mortality rate was 12.5%. [corrected] There were no procedure-related
      complications. During mean follow-up of 9 months, 1 patient developed recurrent
      bleeding that was managed conservatively. COMMENTS: Endovascular embolization is
      a safe alternative to open surgical intervention after failed endoscopic
      treatment for UGIB. Surgeons with endovascular skills can perform this procedure
      with superior results.

PMID- 19178902
TI  - Laparoscopic mesh-augmented hiatoplasty as a method to treat gastroesophageal
      reflux without fundoplication: single-center experience with 306 consecutive
      patients.
AB  - BACKGROUND: Laparoscopic fundoplication represents the surgical standard
      treatment of gastroesophageal reflux disease. However, because of persisting side
      effects the method is not without controversy. Laparoscopic mesh-augmented
      hiatoplasty might be an alternative. METHODS: In 306 consecutive patients the
      perioperative course and symptomatic outcome was analyzed after a mean follow-up
      period of 52 months. RESULTS: The mean DeMeester symptom score decreased from 5.3
      to 2.0 (P < .001). Acid-suppressive therapy on a regular basis was discontinued
      in 79% of patients. The gas bloating value decreased from .7 to .5 (P = .031),
      and the dysphagia value increased from .5 to .9 (P < .001). Belching and vomiting
      were possible in 93% and 88% of patients, respectively. Mesh-related
      complications with the need for reoperation occurred in 1% of patients.
      CONCLUSIONS: Laparoscopic mesh-augmented hiatoplasty is safe and does have an
      antireflux effect even without fundoplication. Side effects seem to be
      reasonable.

PMID- 19178903
TI  - Outcome of chronic pilonidal disease treatment after ambulatory plain midline
      excision and primary suture.

PMID- 19178904
TI  - How international electives could save general surgery.

PMID- 19178905
TI  - Management of acute biliary pancreatitis during pregnancy: past and present.

PMID- 19178906
TI  - Preduodenal portal vein with preduodenal common bile duct: an extremely rare
      anomaly.
AB  - Preduodenal portal vein (PDPV) may occur as an isolated event and result in no
      symptoms, or it may found at autopsy as an incidental finding; associated
      preduodenal common bile duct (PDCBD) is an extremely rare event. To the 8
      reported cases of PDPV with PDCBD, we add this rare case. Such a discovery is
      often incidental and of little import; however, it takes on major importance for
      hepatobiliary surgeons because the accidental damage of PDPV with PDCBD can lead
      to serious consequences. In addition to describing and illustrating this case, we
      discuss its relevant anatomy, embryology and associated malformations.

PMID- 19178907
TI  - [Inborn errors of metabolism in adults].
AB  - We present a simplified classification of treatable inborn errors of metabolism
      (IEM) in three groups with a special focus on those disorders observed at adult
      age. Group 1 includes inborn errors (IE) of intermediary metabolism which give
      rise to an acute or chronic intoxication. It encompasses aminoacidopathies,
      organic acidurias (OA), urea cycle disorders (UCD), sugar intolerances, metal
      storage disorders and porphyrias. Clinical expression can be acute, systemic or
      involves a specific organ, it can strike in the neonatal period or later and
      intermittently from infancy to late adulthood. Most of these disorders are
      treatable and require the emergency removal of the toxin by special diets,
      extracorporeal procedures, cleansing drugs or vitamins. Group 2 includes IE of
      intermediary metabolism which affect the cytoplasmic and mitochondrial energetic
      processes. Cytoplasmic defects encompass those affecting glycolysis,
      glycogenosis, gluconeogenesis, creatine and pentose phosphate pathways; the
      latter are untreatable. Mitochondrial defects include respiratory chain
      disorders, Krebs cycle and pyruvate oxidation defects, mostly untreatable, and
      disorders of fatty acid oxidation and ketone bodies that are treatable. Group 3
      involves cellular organelles and include lysosomal, peroxisomal, glycosylation,
      and cholesterol synthesis defects. Among these, some lysosomal disorders can be
      efficiently treated by enzyme replacement or substrate reduction therapies.
      Physicians can be faced with the possibility of a treatable IE in emergency,
      either in the neonatal period or late in infancy to adulthood, or as chronic and
      progressive symptoms, general (failure to thrive), neurological, or specific for
      various organs or systems. These symptoms and the simplified classification of
      IEM are summarized in seven tables.

PMID- 19178908
TI  - Shape symmetry analysis of breast tumors on ultrasound images.
AB  - Shape characteristics of malignant and benign breast tumors are significantly
      different. In this paper, the reflective symmetry of breast tumor shapes on
      ultrasound images was investigated. A new reflective symmetry measure (RSML)
      derived from multiscale local area integral invariant was proposed to quantify
      the shape symmetry of breast tumor, which could be computed directly from the
      binary mask image without the shape parameterization in terms of arc length. The
      performance of several symmetry measures for differentiating malignant and benign
      breast tumors at varying scales was evaluated and compared by receiver operating
      characteristic (ROC) analysis. RSML with Gaussian kernel at scale 0.04 (related
      to the maximal diameter) achieved the highest area under the ROC curve (0.85) on
      the image data of 168 tumors (104 benign and 64 malignant). The experimental
      results showed that the reflective symmetry of breast tumor shape was capable of
      providing potential diagnostic information, which could be characterized
      quantitatively by RSML with the appropriate scale parameter.

PMID- 19178909
TI  - The significance of segmental fibular fractures in the management of associated
      tibial fractures.
AB  - One hundred seventy-six patients with 179 tibial shaft fractures (between March
      2003 and August 2007) with a minimum of 4 months follow up were retrospectively
      reviewed by the author. Twenty-nine of these fractures were found to have
      segmental fibular fractures. These 29 fractures were analysed and compared with
      the total of 179 tibial fractures. Segmental tibial fractures with and without
      segmental tibial comminution were also analysed and compared. The segmental
      fibular fracture group had a greater incidence of associated injuries, associated
      fractures, open tibial fractures, Gustilo III B type fractures, major flap
      procedures, bony infection and bone grafting procedures which was statistically
      significant. The coincidence of segmental fibular fractures and segmental tibial
      fracture with segmental comminution indicated a bad prognosis. Segmental fibular
      fracture (associated with tibial fracture) appear more severe injury than
      segmental tibial fracture.

PMID- 19178910
TI  - A multifunctional dual membrane electrodialytic eluent generator for capillary
      ion chromatography.
AB  - A multifunctional electrodialytic generator (EDG) for capillary ion
      chromatography (CIC) is described. The same device can generate acidic, basic or
      saline eluents. Two oppositely charged ion exchange beads are used to fabricate
      the EDG; the dual ion exchanger configuration ensures the production of gas-free
      eluent, obviating the need of a gas removal device used with single ion exchanger
      EDG's. The ability of the same EDG to produce different eluents is governed
      solely by the choice of the respective feed solutions; this is presently
      demonstrated by generation of diverse eluents such as Na(2)CO(3)/NaHCO(3),
      CH(3)SO(3)H, and KNO(3). The EDG is implemented simply in a commercial cross
      fitting and has been tested up pressures to 2000psi. Under typical operating
      conditions, the zero current concentration (open circuit penetration, OCP) is
      negligible. The generated eluent concentration linearly increases with applied
      current with a slope that is essentially Faradaic. The device permits both
      isocratic and gradient operation with good reproducibility, as demonstrated by
      the analysis of anions using HCO(3)(-)/CO(3)(2-) EDG.

PMID- 19178911
TI  - Fourier transform infrared spectroscopy and solid-state nuclear magnetic
      resonance studies of octadecyl modified metal oxides obtained from different
      silane precursors.
AB  - Octadecyl (C(18)) modified metal oxide substrates, including titania, zirconia,
      hafnia, and alumina, are prepared using two types of silylating reagents, n
      octadecyltrihydridosilane and n-octadecyltrichlorosilane. Fourier transform
      infrared (FTIR) and solid-state (29)Si nuclear magnetic resonance (NMR)
      measurements are performed to examine the cross-linking of the silanes. Solid
      state (13)C NMR spectroscopy provides information about the conformation and
      mobility of surface-immobilized alkyl chains. Variable temperature FTIR
      investigations are carried out to study the influence of the organosilane
      precursors and metal oxides on the conformational order of the alkyl modified
      systems. It is found that grafting by means of n-octadecyltrichlorosilane yields
      higher grafting densities than surface modification with n
      octadecyltrihydridosilane. Combined pyridine adsorption and diffuse reflectance
      infrared Fourier transform (DRIFT) measurements are performed on the titania and
      hafnia substrates to evaluate potential surface heterogeneities, i.e. Lewis and
      Bronsted sites. Differences in the alkyl chain conformational order within the
      series of C(18) modified metal oxides are explained by the presence of island
      structures. The reduced C(18) conformational order for the samples grafted with n
      octadecyltrihydridosilane is traced back to the lower grafting density which in
      turn points to a lower reactivity of this silylating reagent. The most striking
      result is the higher conformational order of the C(18) chains grafted in the
      present surface modified metal oxides when compared with silica-based systems.
      This finding is attributed to the lower porosity of the metal oxide supports
      along with more closely packed chains on the surface.

PMID- 19178912
TI  - Dynamic control of protein conformation transition in chromatographic separation
      based on hydrophobic interactions: molecular dynamics simulation.
AB  - Conformational transitions of a protein in hydrophobic interaction based
      chromatography, including hydrophobic interaction chromatography (HIC) and
      reversed-phase liquid chromatography (RPLC), and their impact on the separation
      process and performance were probed by molecular dynamics simulation of a 46-bead
      beta-barrel coarse-grained model protein in a confined pore, which represents the
      porous adsorbent. The transition of the adsorbed protein from the native
      conformation to an unfolded one occurred as a result of strong hydrophobic
      interactions with the pore surface, which reduced the formation of protein
      aggregates. The conformational transition was also displayed in the simulation
      once an elution buffer characterized by weaker hydrophobicity was introduced to
      strip protein from pore surface. The discharged proteins that underwent
      conformational transition were prone to aggregation; thus, an unsatisfactory
      yield of the native protein was obtained. An orthogonal experiment revealed that
      in addition to the strengths of the protein-protein and protein-adsorbent
      hydrophobic interactions, the elution time required to reduce the above-mentioned
      interactions also determined the yield of native protein by HIC and RPLC.
      Stepwise elution, characterized by sequential reduction of the hydrophobic
      interactions between the protein and adsorbent, was presented as a dynamic
      strategy for tuning conformational transitions to favor the native conformation
      and reduce the formation of protein aggregates during the elution process. The
      yield of the native protein obtained by this dynamic operation strategy was
      higher than that obtained by steady-state elution. The simulation study
      qualitatively reproduced the experimental observations and provided molecular
      insight that would be helpful for designing and optimizing HIC and RPLC
      separation of proteins.

PMID- 19178913
TI  - High-throughput approach for analysis of multicomponent gas chromatographic-mass
      spectrometric signals.
AB  - Hyphenated techniques such as gas chromatography-mass spectrometry (GC-MS) or
      high-performance liquid chromatography-mass spectrometry (LC-MS) produce a large
      amount of data in a form of two-way data matrix. It has been a great challenge to
      furthest extract the useful information from the data. In this work, a
      chemometric approach based on a modification of adaptive immune algorithm (AIA)
      was proposed for a high-throughput analysis of the multicomponent overlapping GC
      MS signals. With the proposed method, the chromatographic profile of each
      component in an overlapping signal can be extracted independently and
      sequentially along the retention time. In order to show the efficiency of the
      method, a stimulated GC-MS data of six components with background and an
      experimental GC-MS data of 40 pesticides were investigated. It was found that the
      multicomponent overlapping GC-MS signals could be fast and accurately resolved.
      Furthermore, the quantitative property of the extracted information was also
      investigated. The correlation coefficients (r) between the peak area and the
      added volumes of the sample are in the range 0.9658-0.9953.

PMID- 19178915
TI  - Ternary AOT/water/hexane systems as "micellar sieves" for cyanine dye J
      aggregates.
AB  - We investigate the behavior of J-aggregates of a cyanine dye, 3,3(')-di-(gamma
      sulfopropyl)-4,5,4('),5(')-dibenzo-9-ethylthiacarbocyanine betaine pyridinium
      salt, in AOT/water/hexane reverse micelles (W=2-50), both during the course of
      rapid microemulsion formation and then after stabilization of the microemulsions
      at thermodynamic equilibrium. We suggest a new mechanism for J-aggregate
      formation in reverse micelle solutions. According to this model J-aggregates are
      formed in the aqueous phase prior to formation of a stable microemulsion, rather
      than in the process of intermicellar exchange. Reverse micelles encapsulate only
      those J-aggregates whose size is smaller than the mean size of the water pool.
      Larger J-aggregates located in hexane gradually precipitate from solution. It is
      demonstrated that micellar solutions can be used as "sieves" for selection and
      stabilization of J-aggregates with a desired size.

PMID- 19178914
TI  - Novel zwitterionic polyphosphorylcholine monolithic column for hydrophilic
      interaction chromatography.
AB  - A novel porous zwitterionic monolith was prepared by thermal co-polymerisation of
      2-methacryloyloxyethyl phosphorylcholine (MPC) and ethylene glycol dimethacrylate
      (EDMA) within 100 microm I.D. capillaries. Mercury intrusion porosimetry,
      scanning electron microscopy (SEM), micro-HPLC (micro-HPLC), elemental analysis
      and zeta-potential analysis were used to evaluate the monolithic structure. No
      evidence of swelling or shrinking of the monolith in different polarity solvents
      was observed. A typical hydrophilic liquid chromatography (HILIC) mechanism was
      observed at high organic solvent content (acetonitrile >60%). The
      phosphorylcholine (PC) functionality has both a positively charged quaternary
      ammonium and a negatively charged phosphate group. For charged analytes, a weak
      electrostatic interaction was also observed by studying the influence of mobile
      phase pH and salt concentration on their retentions on the poly(MPC-co-EDMA)
      monolithic column. The optimised poly(MPC-co-EDMA) monolith showed very good
      selectivities for a range of polar test analytes, especially small peptides. This
      might be ascribed to the good biocompatibility of PC functionality. At low
      organic solvent content, baseline separation was also observed for a test mixture
      of seven alkylphenones by a reversed-phase separation mechanism.

PMID- 19178916
TI  - Spinal cord lesions and clinical status in multiple sclerosis: A 1.5 T and 3 T
      MRI study.
AB  - OBJECTIVE: Assess the relationship between spinal cord T2 hyperintense lesions
      and clinical status in multiple sclerosis (MS) with 1.5 and 3 T MRI. METHODS:
      Whole cord T2-weighted fast spin-echo MRI was performed in 32 MS patients
      [Expanded Disability Status Scale (EDSS) score (mean+/-SD: 2+/-1.9), range 0
      6.5]. Protocols at 1.5 T and 3 T were optimized and matched on voxel size.
      RESULTS: Moderate correlations were found between whole cord lesion volume and
      EDSS score at 1.5 T (r(s)=.36, p=0.04), but not at 3 T (r(s)=0.13, p=0.46).
      Pyramidal Functional System Score (FSS) correlated with thoracic T2 lesion number
      (r(s)=.46, p=0.01) and total spinal cord lesion number (r(s)=0.37, p=0.04) and
      volume (r(s)=0.37, p=0.04) at 1.5 T. Bowel/bladder FSS correlated with T2 lesion
      volume and number in the cervical, thoracic, and total spine at 1.5 T (r(s) 0.40
      0.57, all p<0.05). These MRI-FSS correlations were non-significant at 3 T.
      However, these correlation coefficients did not differ significantly between
      platforms (Choi's test p>0.05). Correlations between whole cord lesion volume and
      timed 25-foot walk were non-significant at 1.5 T and 3 T (p>0.05). Lesion number
      and volume did not differ between MRI platforms in the MS group (p>0.05).
      CONCLUSIONS: Despite the use of higher field MRI strength, the link between
      spinal lesions and MS disability remains weak. The 1.5 T and 3 T protocols
      yielded similar results for many comparisons.

PMID- 19178917
TI  - Ecological risk of Irgarol 1051 and its major metabolite in coastal California
      marinas and reference areas.
AB  - The objective of this study was to use a probabilistic approach to determine the
      ecological risk of Irgarol and its major metabolite (GS26575) in coastal
      California marinas and reference areas by using monitoring data collected during
      the summer of 2006. Distributions of environmental exposure data were compared
      with the distribution of plant species response data from laboratory toxicity
      studies and the no observed effect concentration (NOEC) from a microcosm study to
      quantify the likelihood and significance of ecological risk. Toxicity testing
      indicates plants are much more sensitive to Irgarol than animals; therefore, the
      conservative effects benchmark used to characterize risk was the plant 10th
      centile for both Irgarol (193 ng/L) and GS26575 (5622 ng/L). In addition, the
      microcosm NOEC of 323 ng/L was also used to characterize risk. Irgarol
      concentrations from 15 California marinas ranged from 1.45 to 339 ng/L while
      GS26575 concentrations ranged from non-detected to 74 ng/L. The probability of
      exceeding the Irgarol plant 10th centile of 193 ng/L for 15 marinas sampled in
      coastal California in 2006 was 7.3% while the probability of exceeding the
      microcosm NOEC of 323 ng/L was even lower (5.5%). In general, this probability of
      exceedence for either effects benchmark and subsequent ecological risk is
      considered to be low for these marinas as only one marina (Kings Harbor marina in
      Redondo Beach) had measured concentrations of Irgarol exceeding 193 ng/L. Irgarol
      exposure is concentrated within marinas and ecological risk from Irgarol exposure
      in adjoining reference areas was judged to be very low. Ecological risk from
      GS26575 exposure was also low in both marina and reference areas in California.

PMID- 19178918
TI  - Medium-term assessment of the effects of the Prestige oil spill on estuarine
      benthic communities in Cantabria (Northern Spain, Bay of Biscay).
AB  - A specific monitoring program was implemented in the estuaries of Cantabria
      (northern Spain) in order to assess the medium-term effects (2003-2005) of the
      Prestige oil spill (POS) on benthic macroinvertebrate communities. A control
      impact design was adopted, examining four unaffected and five oil-affected
      estuaries. High mortalities and significant differences in overall richness and
      diversity between the control and impacted estuaries were not detected. Some
      changes in the temporal evolution of species abundance were observed for some key
      species, but these could not be related to the spillage event. It was not
      possible to ensure that low magnitude effects had not occurred, due to the high
      range of natural variability of benthic communities, the confounding effects of
      other contamination sources and the absence of previous reference conditions.

PMID- 19178919
TI  - Evidence for a relationship between Leishmania load and clinical manifestations.
AB  - Visceral leishmaniasis (VL) is a life-threatening disease of medical, social and
      economic importance in endemic areas. Dogs are the main reservoir of
      Leishmaniainfantum. In this study, the authors investigated a group of 56 natural
      infected dogs to establish the relationship between parasite load and various
      clinical forms of leishmaniasis. The sick dogs were monitored at the beginning
      from clinical and physiological point of view. Leishmania load was measured by
      real-time PCR assay on whole blood samples and lymph node aspirates, collected at
      the time of diagnosis. Our results indicate that a higher quantity of Leishmania
      DNA was found in the lymph nodes of dogs characterized by maximum clinical score.
      This interesting finding indicates the presence of a positive relationship
      between Leishmania load and clinical manifestations in dogs showing a severe
      clinical form of leishmaniasis.

PMID- 19178920
TI  - Evaluation of three years of the SAFE strategy (Surgery, Antibiotics, Facial
      cleanliness and Environmental improvement) for trachoma control in five districts
      of Ethiopia hyperendemic for trachoma.
AB  - Trachoma surveys were conducted at baseline in five districts of Amhara National
      Regional State, Ethiopia (7478 participants in 1096 households) and at 3-year
      evaluation (5762 participants in 1117 households). Uptake of SAFE was assessed
      with programme monitoring data and interviews, and children (1-6 years) were
      swabbed for detection of ocular Chlamydia. At evaluation, 23,933 people had
      received trichiasis surgery; 93% of participants reported taking azithromycin at
      least once; 67% of household respondents (range 46-93) reported participation in
      trachoma health education; and household latrine coverage increased from 2% to
      34%. In children aged 1-9 years percentage decline, by district, for outcomes
      was: 32% (95% CI 19-48) to 88% (95% CI 83-91) for trachomatous inflammation
      follicular (TF); 87% (95% CI 83-91) to 99% (95% CI 97-100) for trachomatous
      inflammation-intense (TI); and 31% increase (95% CI -42 to -19) to 89% decrease
      (95% CI 85-93) for unclean face; and in adults percentage decline in trichiasis
      was 45% (95% CI -13 to 78) to 92% (95% CI 78-96). Overall prevalence of swabs
      positive for ocular Chlamydia was 3.1%. Although there were substantial
      reductions in outcomes in children and adults, the presence of ocular Chlamydia
      and TF in children suggests ongoing transmission. Continued implementation of
      SAFE is warranted.

PMID- 19178921
TI  - Natural infection of Nyssomyia neivai (Pinto, 1926) (Diptera: Psychodidae,
      Phlebotominae) by Leishmania (Viannia) spp. in Brazil.
AB  - A study of the natural infection of phlebotomine sand flies by Leishmania
      (Viannia) was conducted in a focus of cutaneous leishmaniasis in Picarras, on the
      northeastern coast of the Brazilian state of Santa Catarina. In total, 562 female
      Nyssomyia neivai were collected by miniature light traps near houses, separated
      in 61 pools and examined by PCR and Southern blot hybridization. Eight pools,
      four of them from the same light trap/night, were positive. This is the first
      finding of natural infection by Le. braziliensis of adequately identified Ny.
      neivai in Brazil. In this preliminary observation we observed the abundance and
      predominance of Ny. neivai among the captured phlebotomine species (98.5%),
      indicating that Ny. neivai may be the dominant vector of Leishmania in the
      subgenus Viannia in this area.

PMID- 19178922
TI  - Socio-economic status by rapid appraisal is highly correlated with mortality
      risks in rural Africa.
AB  - Socio-economic status is an important determinant of health and survival in rural
      Africa and necessitates a practical and valid instrument to implement in health
      studies. Our objective was to investigate the validity of the rapid appraisal
      method to assess socio-economic status and its ability to identify individuals at
      risk. Among 1573 households in rural northern Ghana, we calculated the
      Demographic Health Survey (DHS) wealth index and conducted two rapid appraisal
      methods: self-reported wealth and interviewer-reported wealth. In addition we
      followed the 25,184 participants from these households for survival with a mean
      follow-up of 3.9 years, during which 885 participants died. The DHS wealth index
      was moderately correlated to self-reported wealth (Spearman's rho 0.59, P<0.001)
      and interviewer-reported wealth (Spearman's rho 0.75, P<0.001). Mortality risks
      were significantly higher for people with lower than average self-reported wealth
      [hazard ratio (HR) 1.30 (95% CI 1.11-1.51)] and lower interviewer-reported wealth
      [HR 1.40 (95% CI 1.21-1.62)]. Mortality risks were lower for people with higher
      self-reported wealth [HR 0.81 (95% CI 0.32-2.03)] and higher interviewer-reported
      wealth [HR 0.84 (95% CI 0.58-1.21)]. Similar discriminative mortality risks were
      assessed when using tertiles of the DHS wealth index (Ptrend<0.001).

PMID- 19178923
TI  - Interaction of the replication proteins and the capsid protein of porcine
      circovirus type 1 and 2 with host proteins.
AB  - Porcine circovirus type 2 (PCV2) is an important pathogen in swine, whereas
      porcine circovirus type 1 (PCV1) is apathogenic. To analyze the interactions
      between PCV and its host, we have used a yeast two-hybrid assay to identify
      cellular proteins interacting with Cap and Rep proteins of both PCV genotypes.
      Six cellular proteins were found to interact with Cap (MKRN1, gC1qR, Par-4, NAP1,
      NPM1 and Hsp40) and three with Rep (ZNF265, TDG and VG5Q). These interactions
      were confirmed by co-immunoprecipitation. Investigation of the localisation of
      the proteins by immunofluorescence revealed in some cases only limited spatial
      overlapping with Cap, while in others a clear co-localisation and prominent
      protein redistribution was observed. The nine cellular proteins are associated
      with distinct aspects of viral lifecycle and our data is likely to support future
      research in the field of PCV2 pathogenesis.

PMID- 19178924
TI  - Evidence that selective changes in the lipid composition of raft-membranes occur
      during respiratory syncytial virus infection.
AB  - We examined the structure of lipid-raft membranes in respiratory syncytial virus
      infected cells. Cholesterol depletion studies using methyl-beta-cyclodextrin
      suggested that membrane cholesterol was required for virus filament formation,
      but not inclusion bodies. In addition, virus filament formation coincided with
      elevated 3-hydroxy-3-methylglutaryl-coenzyme A reductase expression, suggesting
      an increase in requirement for endogenous cholesterol synthesis during virus
      assembly. Lipid raft membranes were examined by mass spectrometry, which
      suggested that virus infection induced subtle changes in the lipid composition of
      these membrane structures. This analysis revealed increased levels of raft
      associated phosphatidylinositol (PI) and phosphorylated PI during RSV infection,
      which correlated with the appearance of phosphatidylinositol 4,5-bisphosphate and
      phosphatidylinositol 3,4,5-triphosphate (PIP(3)) within virus inclusion bodies,
      and inhibiting the synthesis of PIP(3) impaired the formation of progeny virus.
      Collectively, our analysis suggests that RSV infection induces specific changes
      in the composition of raft-associated lipids, and that these changes play an
      important role in virus maturation.

PMID- 19178925
TI  - Raft localization of CXCR4 is primarily required for X4-tropic human
      immunodeficiency virus type 1 infection.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection is initiated by successive
      interactions of viral envelope glycoprotein gp120 with two cellular surface
      proteins, CD4 and chemokine receptor. The two most common chemokine receptors
      that allow HIV-1 entry are the CCR5 and CXCR4. The CD4 and CCR5 are mainly
      localized to the particular plasma membrane microdomains, termed raft, which is
      rich in glycolipids and cholesterol. However, the CXCR4 is localized only
      partially to the raft region. Although the raft domain is suggested to
      participate in HIV-1 infection, its role in entry of CXCR4-tropic (X4-tropic)
      virus is still unclear. Here, we used a combination of CD4-independent infection
      system and cholesterol-depletion-inducing reagent, methyl-beta-cyclodextrin
      (MbetaCD), to address the requirement of raft domain in the X4-tropic virus
      infection. Treatment of CD4-negative, CXCR4-positive human cells with MbetaCD
      inhibited CD4-independent infection of the X4-tropic strains. This inhibitory
      effect of the cholesterol depletion was observed even when the CXCR4 was over
      expressed on the target cells. Soluble CD4-induced infection was also inhibited
      by MbetaCD. The MbetaCD had no effect on the levels of cell surface expression of
      CXCR4. In contrast to these infections, MbetaCD treatment did not inhibit CD4
      dependent HIV-1 infection in the wild type CD4-expressing cells. This study and
      previous reports showing that CD4 mutants localized to non-raft domains function
      as HIV-1 receptor indicate that CXCR4 clustering in the raft microdomains, rather
      than CD4, is the key step for the HIV-1 entry.

PMID- 19178926
TI  - Recent advances in membrane bioreactors (MBRs): membrane fouling and membrane
      material.
AB  - Membrane bioreactors (MBRs) have been actively employed for municipal and
      industrial wastewater treatments. So far, membrane fouling and the high cost of
      membranes are main obstacles for wider application of MBRs. Over the past few
      years, considerable investigations have been performed to understand MBR fouling
      in detail and to develop high-flux or low-cost membranes. This review attempted
      to address the recent and current developments in MBRs on the basis of reported
      literature in order to provide more detailed information about MBRs. In this
      paper, the fouling behaviour, fouling factors and fouling control strategies were
      discussed. Recent developments in membrane materials including low-cost filters,
      membrane modification and dynamic membranes were also reviewed. Lastly, the
      future trends in membrane fouling research and membrane material development in
      the coming years were addressed.

PMID- 19178927
TI  - Phosphorus sorption experiments and the potential for internal phosphorus loading
      in littoral areas of a stratified lake.
AB  - The exchange of phosphorus (P) during the resuspension of sediments into shallow
      (oxic) waters of deep stratified lakes is regulated by equilibrium dynamics. In
      this study, we compared the P-sorption characteristics of sediments from 17
      shallow and deep littoral sites in an oligo-mesotrophic lake. Zero Equilibrium P
      Concentration (EPC(0)) ranged from 0.2 to 5 microgPL(-1). EPC(0) did not vary
      with sediment characteristics, but increased with increasing sediment-to-water
      ratios (SWR). Buffering capacity also increased with increasing SWR up to 1 gL(
      1), at which point P concentrations were buffered almost perfectly. Therefore,
      internal P loading in littoral areas may depend primarily on the intensity and
      duration of sediment resuspension instead of sediment composition, and is
      expected to be spatially and temporally patchy. Maximum P-sorption capacity
      (S(max)) varied with chemical composition of the sediments, but was generally
      low, indicating a limited capacity of littoral sediments to retain external
      inputs of P.

PMID- 19178928
TI  - Comparison of the heterogeneity within bulk sediment humic substances from a
      stream and reservoir via selected operational descriptors.
AB  - The heterogeneity within a bulk humic substances (HS) of two sediment HS from
      different sources (stream and reservoir) was compared using selected operational
      descriptors for ultrafiltration (UF) fractions. The operational descriptors
      investigated included the specific UV absorbance (SUVA), the C/N ratio, the ratio
      of humic-like/fulvic-like fluorescence (HLF/FLF), the humification index (HIX),
      the molecular weight (MW) and the organic carbon normalized pyrene binding
      coefficient (K(oc)). The UF fractions exhibited a linear or a log-linear trend
      with respect to MW for most operational descriptors. The two sediment HS
      exhibited similar patterns in the fluorescence excitation-emission matrix (EEM).
      The trends among some operational descriptors of the UF fractions based on one HS
      source were not the same as those obtained from the other HS source. For the C/N
      ratio, HLF/FLF, and the pyrene binding reactivity, the UF fractions of the stream
      sediment HS had higher values than those of the reservoir sediment HS UF
      fractions. For SUVA and HIX, however, a single relationship was presented with MW
      irrespective of HS sources. This indicates that SUVA and HIX may be more related
      to MW of the sediment HS than to the chemical nature and/or the source. A common
      strong correlation between HLF/FLF and pyrene K(oc) was also observed for the UF
      fractions of the two HS, suggesting that HLF/FLF might serve as a good descriptor
      to predict the extent of pyrene binding independent of sediment source.

PMID- 19178929
TI  - Enhanced bioremediation of methyl tert-butyl ether (MTBE) by microbial consortia
      obtained from contaminated aquifer material.
AB  - A microcosm study was carried out to evaluate the potential for biodegradation of
      methyl tert-butyl ether (MTBE) impacting groundwater at a former oil refinery
      site located in Naples (SW Italy). A screening of aerobic, anaerobic and co
      metabolic aerobic conditions was carried out by triplicate batch reactors, using
      contaminated soil and groundwater from the study site. All microcosms were
      amended with ammonium and phosphate salts and, if aerobic, they were supplied
      with excess oxygen throughout the static incubation period of 6 months. Propane,
      pentane and n-hexane were selected as the primary substrates for co-metabolic
      treatments. After the initial lag phase (40-60d), quantitative MTBE decay was
      repeatedly observed in the aerobic set amended only with nitrogen and phosphorus
      and further fed with MTBE, thus suggesting that the indigenous soil bacteria have
      the ability to degrade MTBE. All other treatments, i.e., anaerobic and co
      metabolic aerobic, resulted unsuccessful after incubation extending up to 190d.
      Bacterial consortia in the active microcosms were later enriched and further
      studied through second and third generation batch reactors with no soil, operated
      under continuous mixing for 5-7 months. MTBE degradation rate progressively
      increased with reactor operating time, following a zero order kinetics in the
      concentration range 1-10mgL(-1) and leading to a residual concentration of less
      than 10microgL(-1). The calculated maximum biodegradation rate was
      20mg(MTBE)g(VSS)(-1)h(-1). An accumulation of nitrite ions also occurred after
      long operating times, thus inhibiting MTBE degradation. This effect was minimized
      by replacing ammonium with nitrate. Identified degradation intermediates were
      tert-butyl alcohol and tert-butyl formate. Fluorescent in situ hybridization was
      applied for a preliminary microbiological screening of the consortia, suggesting
      that the detected cocci (about 0.5 and 1.5microm diameter, respectively) and long
      bacilli with a narrow diameter might be as yet undescribed species.

PMID- 19178930
TI  - Distribution of polybrominated diphenyl ethers in breast milk from North China:
      implication of exposure pathways.
AB  - The breast milk concentrations of polybrominated diphenyl ethers (PBDEs; sum of
      eight congeners: BDE-28, 47, 99, 100, 153, 154, 183 and 209) were determined (by
      high resolution gas chromatographic high resolution mass spectrometry) in samples
      from primiparous women collected in 2006 in Tianjin, China. Dietary and lifestyle
      habits of the participants were obtained by questionnaires. The median total PBDE
      concentration (including BDE-28, 47, 99, 100, 153, 154, 183) was 2500 pg g(-1)
      lipid weight, ranging from 1700 to 4500 pg g(-1) lipid weight. These levels were
      in the same range as those from Europe and Japan but much lower than those from
      North America. The congener profile in China was also different from other
      countries. The contribution of BDE-28 was around 15%, much higher than any other
      country, implying that a different Penta-BDE formulation might be used in the
      Chinese market. The lower ratio of the sum of BDE-47, 99, and 100 to the sum of
      BDE-153 and 154 suggested that Octa-products were in more demand in China. A
      significant correlation was found between a woman's PBDE concentration and the
      time she used electronic appliances (h/d). This implies that electronics are a
      potential source of PBDEs to people. Inhalation or ingestion of particulate
      matter (such as dust) may also be an important exposure pathway. There was no
      significant correlation between the PBDE concentration and the consumption of
      meat, fish, and milk. Further research is needed to determine the specific
      contribution of each exposure route and their health effects.

PMID- 19178931
TI  - Antibiotics in the aquatic environment--a review--part II.
AB  - Although antibiotics have been used in large quantities for some decades, until
      recently the existence of these substances in the environment has received little
      notice. It is only in recent years that a more complex investigation of
      antibiotic substances has been undertaken in order to permit an assessment of the
      environmental risks they may pose. Within the last decade, an increasing number
      of studies covering antibiotic input, occurrence, fate and effects have been
      published. Antibiotics are one of the most important groups of pharmaceuticals.
      Antibiotic resistance is one of the major challenges for human medicine and
      veterinary medicine. However, there is still a lack of understanding and
      knowledge about sources, presence and significance of resistance of bacteria
      against antibiotics in the aquatic environment despite the numerous studies
      performed. This review summarizes this topic. It names important open questions
      and addresses some significant issues which must be tackled in the future for a
      better understanding of resistance related to antibiotics in the environment.

PMID- 19178932
TI  - Potential effects of desalinated water quality on the operation stability of
      wastewater treatment plants.
AB  - Desalinated water is expected to become the major source of drinking water in
      many places in the near future, and thus the major source of wastewater to arrive
      at wastewater treatment plants. The paper examines the effect of the alkalinity
      value with which the water is released from the desalination plant on the
      alkalinity value that would develop within the wastewater treatment process under
      various nitrification-denitrification operational scenarios. The main hypothesis
      was that the difference in the alkalinity value between tap water and domestic
      wastewater is almost exclusively a result of the hydrolysis of urea
      (NH(2)CONH(2), excreted in the human urine) to ammonia (NH(3)), regardless of the
      question what fraction of NH(3(aq)) is transformed to NH(4)(+). Results from a
      field study show that the ratio between the alkalinity added to tap water when
      raw wastewater is formed (in meq/l units) and the TAN (total ammonia nitrogen,
      mole/l) concentration in the raw wastewater is almost 1:1 in purely domestic
      sewage and close to 1:1 in domestic wastewater streams mixed with light industry
      wastewaters. Having established the relationship between TAN and total alkalinity
      in raw wastewater the paper examines three theoretical nitrification
      denitrification treatment scenarios in the wastewater treatment plant (WWTP). The
      conclusion is that if low-alkalinity desalinated water constitutes the major
      water source arriving at the WWTP, external alkalinity will have to be added in
      order to avoid pH drop and maintain process stability. The results lead to the
      conclusion that supplying desalinated water with a high alkalinity value (e.g. >
      or =100 mg/l as CaCO(3)) would likely prevent the need to add costly basic
      chemicals in the WWTP, while, in addition, it would improve the chemical and
      biological stability of the drinking water in the distribution system.

PMID- 19178933
TI  - A controlled study of mental distress and somatic complaints after risk-reducing
      salpingo-oophorectomy in women at risk for hereditary breast ovarian cancer.
AB  - OBJECTIVES: Risk-reducing salpingo-oophorectomy (RRSO) provides effective
      protection against ovarian cancer in BRCA mutation carriers and in women at risk
      for hereditary breast ovarian cancer, but little is known about non-oncologic
      morbidity after the procedure. We explored mental distress and somatic complaints
      in women after RRSO compared to controls from the general population. METHODS:
      503 women from hereditary breast ovarian cancer families who had undergone RRSO
      after genetic counseling received a mailed questionnaire. 361 (71%) responded and
      338 (67%) delivered complete data (cases). Controls were five randomly allocated
      age-matched controls per case (N=1690) from the population-based Norwegian Nord
      Trondelag Health Study (HUNT-2). RESULTS: Mean age of cases and controls was 54.6
      years at survey. Mean time since surgery was 5.3 years (median 6.0). Compared to
      controls, the RRSO group had more palpitations (p=0.02), constipation (p=0.01),
      pain and stiffness (p=0.02), osteoporosis (p=0.02) and musculoskeletal disease
      (p=0.01) even after adjustments for demographic factors including use of hormonal
      replacement therapy. The RRSO group had lower levels of depression (p<0.001) and
      total mental distress (p=0.002) compared to controls. In multivariate linear
      regression analyses, RRSO was associated with lower levels of depression
      (p<0.001) and total mental distress (p=0.002). CONCLUSIONS: In this controlled
      observational study, we found more somatic morbidity such as osteoporosis,
      palpitations, constipation, musculoskeletal disease and pain and stiffness but
      lower levels of mental distress among women who had undergone RRSO compared to
      controls.

PMID- 19178934
TI  - Prognostic value of estrogen receptor and progesterone receptor status in young
      Chinese ovarian carcinoma patients.
AB  - OBJECTIVE: The purpose of this study was to investigate the expression patterns
      and prognostic impact of estrogen receptor (ER), progesterone receptor (PR) and
      their combinations in young patients with ovarian carcinomas (OC) in China.
      METHODS: We collected data on 86 patients diagnosed of OC younger than or equal
      to 40 years of age with a long clinical follow-up. Immunohistochemical staining
      was performed to assess ER and PR expression in paraffin-embedded ovarian
      cancers. Samples in which more than 10% of cells showed stained nuclei were
      interpreted as positive for the particular receptor. Survival rates (Kaplan-Meier
      method) were compared by the log rank test. A multivariate analysis (Cox
      proportional hazards) was used to determine the independent effect of each
      variable on survival. RESULTS: ER were found positive in 64.0% of all cases but
      most highly expressed in serous types (P=0.047). PR-positive expression accounted
      for 57.0% of all cases and elevated in early FIGO stages and well-differentiated
      diseases (P=0.004 and 0.012, respectively). The expression of PR, but not ER, was
      associated with favorable survival in Kaplan-Meier survival analyses (P<0.001).
      The ER+PR+ combination, which was associated with low FIGO stages (P=0.012) and
      low tumor grade (P=0.046), showed a superior course of patients' overall survival
      compared with all other combinations (5-year survival rate 95.0% vs. 73.4%, log
      rank P=0.001). PR status (hazard ratio 1.93, P<0.001) together with FIGO stage
      (hazard ratio 2.19, P<0.001) were proved to be independent prognostic factors by
      multivariate analysis. CONCLUSIONS: This study indicates that the expression of
      PR, especially the ER+PR+ phenotype predicts a favorable clinical outcome for
      young patients of OC.

PMID- 19178935
TI  - Differentiation and functional analysis of human T(H)17 cells.
AB  - BACKGROUND: T(H)17 cells are of pathologic relevance in autoimmune disorders and
      presumably also in allergy and asthma. Regulatory T (Treg) cells, in contrast,
      suppress inflammatory and allergen-driven responses. Despite these disparate
      functions, both T-cell subsets have been shown to be dependent on TGF-beta for
      their development. OBJECTIVE: The aim of the study was to analyze the
      differentiation and function of human T(H)17 cells in comparison with other T(H)
      cell subsets. METHODS: Naive human CD4(+) T cells were differentiated in vitro,
      and gene expression was analyzed by means of quantitative real-time PCR, ELISA,
      and immunofluorescence. The function of T(H) cell subsets was assessed by
      monitoring the response of primary bronchial epithelial cells in coculture
      experiments. RESULTS: In vitro differentiated T(H)17 cells differ from Treg and
      other T(H) cells in their potency to induce IL-6 and IL-1beta expression in
      primary bronchial epithelial cells. TGF-beta, IL-1beta, IL-6, and IL-23 are
      necessary during T(H)17 cell differentiation to acquire these functions,
      including IL-17 production. In contrast, TGF-beta alone is necessary and
      sufficient to induce the transcription factor RORC2. This transcription factor,
      previously thought to be specific for T(H)17 cells, is also expressed in Treg
      cells, CD25(+) cells, cytotoxic T cells, and natural killer T cells. CONCLUSION:
      This study demonstrates mechanisms of differentiation to human T(H)17 cells, a
      subset that effectively and uniquely modulates the function of primary bronchial
      epithelial cells.

PMID- 19178936
TI  - Anaphylaxis provoked by ingestion of marshmallows containing fish gelatin.

PMID- 19178938
TI  - Genetic analysis of Factor XII and bradykinin catabolic enzymes in a family with
      estrogen-dependent inherited angioedema.
AB  - BACKGROUND: Recent studies reported a gain-of-function mutation in the gene
      encoding coagulation Factor XII (F12) among 5 German and French families with
      estrogen-associated angioedema who share a common ancestor. The role of this
      factor, additional pathways that might contribute to increased bradykinin levels,
      or both remain to be determined in other families with estrogen-dependent or
      estrogen-associated inherited angioedema. OBJECTIVE: The purpose of this study
      was to determine whether mutations in F12 and polymorphisms in the genes encoding
      aminopeptidase P (APP) and angiotensin I-converting enzyme (ACE), which have been
      associated with increased bradykinin levels, contribute to estrogen-dependent
      inherited angioedema in a large family of Italian origin. METHODS: We screened
      the coding regions of F12 and the gene encoding membrane-bound APP (XPNPEP2), for
      genetic variants in the 3 affected female subjects. In addition, we genotyped
      this family for the insertion/deletion polymorphism in the ACE gene, which
      accounts for variable ACE levels. RESULTS: The 3 affected female subjects all
      have the threonine-to-lysine (Thre328Lys) mutation, which is associated with
      higher Factor XII activity. In addition, they have at least one A allele of
      rs3788853 at the XPNPEP2 locus, which is associated with lower APP activity, and
      at least one I allele in ACE, which is associated with reduced ACE activity.
      CONCLUSION: A missense mutation in F12 is present in the 3 affected female
      subjects of this family with estrogen-dependent inherited angioedema. In
      addition, these affected females have polymorphisms associated with lower levels
      of both APP and ACE, the major enzymes responsible for bradykinin degradation.
      Thus, our study suggests that multiple genes might contribute to estrogen
      dependent or estrogen-associated inherited angioedema and explain some of the
      observed heterogeneity.

PMID- 19178937
TI  - Innate immune responses of airway epithelium to house dust mite are mediated
      through beta-glucan-dependent pathways.
AB  - BACKGROUND: House dust mite (HDM) induces allergic asthma in sensitized
      individuals, although the mechanisms by which HDM is sensed and recognized by the
      airway mucosa, leading to dendritic cell (DC) recruitment, activation, and
      subsequent T(H)2-mediated responses, are unknown. OBJECTIVE: We sought to define
      the pathways by which HDM activates respiratory epithelium to induce allergic
      airway responses. METHODS: Using a human airway epithelial cell line (16HBE14o-),
      we studied secretion of the DC chemokine CCL20 after exposure to HDM or other
      allergens, investigated components of the HDM responsible for the induction of
      chemokine release, and examined activation of signaling pathways. Central
      findings were also confirmed in primary human bronchial cells. RESULTS: We
      demonstrate that exposure of airway epithelium to HDM results in specific and
      rapid secretion of CCL20, a chemokine attractant for immature DCs. The induction
      of CCL20 secretion is dose and time dependent and quite specific to HDM because
      other allergens, such as ragweed pollen and cockroach antigen, fail to
      significantly induce CCL20 secretion. Induction of CCL20 secretion is not
      protease or Toll-like receptor 2/4 dependent but, interestingly, relies on beta
      glucan moieties within the HDM extract, as evidenced by the ability of other beta
      glucans to competitively inhibit its secretion and by the fact that disruption of
      these structures by treatment of HDM with beta-glucanase significantly reduces
      subsequent chemokine secretion. CONCLUSION: Taken together, our results describe
      a novel mechanism for specific pattern recognition of HDM-derived beta-glucan
      moieties, which initiates allergic airway inflammation and, through recruitment
      of DCs, might link innate pattern recognition at the airway surface with adaptive
      immune responses.

PMID- 19178939
TI  - Novel presentation of Omenn syndrome in association with aniridia.

PMID- 19178940
TI  - Brief report: Accuracy of a 16-item questionnaire based on the HEADSS approach
      (QBH-16) in the screening of mental disorders in adolescents with behavioral
      problems in secondary care.
AB  - OBJECTIVE: Compare a questionnaire based on the HEADSS approach (QBH-16) and the
      Child Behavior Checklist (CBCL) in the screening of mental disorder in
      adolescents with behavioral problems. METHODS: Adolescents from both genders 12
      17 years-old presenting behavioral problems without a previous diagnosis of
      mental disorder were referred from primary services to a specialized outpatient
      program for adolescent behavioral problems and evaluated with the QBH-16, CBCL,
      and the Wechsler Intelligence Scale for Children. This program is located in a
      secondary and tertiary university hospital, Hospital de Clinicas de Porto Alegre,
      in the capital city of the southernmost state of Brazil. RESULTS: 98 adolescents
      and their families were interviewed. Scores > or =9 in the QBH-16 had a
      likelihood ratio (LR) >5.5 and scores under 6 had a LR of 0.13, identifying
      adequately 62 patients (71%) according to the CBCL. Cognitive performance was
      similar among all patients. DISCUSSION: Our findings suggest the QBH-16 has a
      good accuracy for screening mental disorders and may help prioritize or choose
      which patients will benefit from psychiatric services.

PMID- 19178941
TI  - Thermosensitive poly(organophosphazene)-paclitaxel conjugate gels for antitumor
      applications.
AB  - A poly(organophosphazene)-PTX conjugate was synthesized by a covalent ester
      linkage between PTX and carboxylic acid-terminated poly(organophosphazene), which
      can be readily modified by various hydrophobic, hydrophilic, and other functional
      substitutes. The physicochemical properties, hydrolytic degradation and PTX
      release behaviors of the polymer-PTX conjugate were characterized, in addition to
      the in vitro and in vivo antitumor activities. The aqueous solutions of these
      conjugates showed a sol-gel transition behavior that depended on temperature
      changes. The in vitro antitumor activity of the polymer-PTX conjugate was
      investigated by an MTT assay against human tumor cell lines. From the in vivo
      antitumor activity studies with tumor-induced (xenografted) nude mice, the
      polymer-paclitaxel conjugate hydrogels after local injection at the tumor site
      were shown to inhibit tumor growth more effectively and longer than paclitaxel
      and saline alone, indicating that the tumor-active paclitaxel from the polymer
      PTX conjugate hydrogel is released slowly over a longer period of time and
      effectively accumulated locally in the tumor sites. These combined observations
      suggest that this poly(organophosphazene)-PTX conjugate holds promise for use in
      clinical studies as single and/or combination therapies.

PMID- 19178942
TI  - The use of combinatorial topographical libraries for the screening of enhanced
      osteogenic expression and mineralization.
AB  - Nano- and microstructured surfaces are known to impact on the binding and
      differentiation of cells, but the detailed basic understanding of the underlying
      regulatory mechanisms is still scarce, which impedes the rational design of smart
      biomaterials. Towards a comprehensive analysis of the interplay between
      topographical parameters such as feature design and lateral and vertical
      dimensions we here report on a combinatorial screening approach, BioSurface
      Structure Array (BSSA) of test squares each with a distinct topography. Using
      such BSSA libraries of 504 topographically distinct surface structures, we have
      identified combinations of size, gap and height of structures which enhance
      mineralization as well as the expression of osteogenic markers of a
      preosteoblastic murine cell line. This generic BSSA screening platform is a
      versatile technology for the systematic identification of surfaces with specific
      biological properties, and it may for example be useful for optimizing the design
      of biomaterials for regulating cellular behaviour.

PMID- 19178943
TI  - Polypyrrole-coated electrodes for the delivery of charge and neurotrophins to
      cochlear neurons.
AB  - Sensorineural hearing loss is associated with gradual degeneration of spiral
      ganglion neurons (SGNs), compromising hearing outcomes with cochlear implant use.
      Combination of neurotrophin delivery to the cochlea and electrical stimulation
      from a cochlear implant protects SGNs, prompting research into neurotrophin
      eluting polymer electrode coatings. The electrically conducting polypyrrole/para
      toluene sulfonate containing neurotrophin-3 (Ppy/pTS/NT3) was applied to 1.7 mm2
      cochlear implant electrodes. Ppy/pTS/NT3-coated electrode arrays stored 2 ng NT3
      and released 0.1 ng/day with electrical stimulation. Guinea pigs were implanted
      with Ppy/pTS or Ppy/pTS/NT3 electrode arrays two weeks after deafening via
      aminoglycosides. The electrodes of a subgroup of these guinea pigs were
      electrically stimulated for 8 h/day for 2 weeks. There was a loss of SGNs in the
      implanted cochleae of guinea pigs with Ppy/pTS-coated electrodes indicative of
      electrode insertion damage. However, guinea pigs implanted with electrically
      stimulated Ppy/pTS/NT3-coated electrodes had lower electrically-evoked auditory
      brainstem response thresholds and greater SGN densities in implanted cochleae
      compared to non-implanted cochleae and compared to animals implanted with Ppy/pTS
      coated electrodes (p<0.05). Ppy/pTS/NT3 did not exacerbate fibrous tissue
      formation and did not affect electrode impedance. Drug-eluting conducting polymer
      coatings on cochlear implant electrodes present a clinically viable method to
      promote preservation of SGNs without adversely affecting the function of the
      cochlear implant.

PMID- 19178944
TI  - 5,10-Methylenetetrahydrofolate reductase (MTHFR) low activity genotypes reduce
      the risk of relapse-related acute lymphoblastic leukemia (ALL).
AB  - The reported correlation of defects in 5,10-methylenetetrahydrofolate reductase
      (MTHFR), the key enzyme of folate metabolism, with modulated risk for acute
      lymphoblastic leukemia (ALL) is ambiguous. We have elucidated the influence of
      MTHFR genotype on ALL development and relapse in 140 Slovenian pediatric ALL
      patients and 183 healthy controls. A decreased proportion of low activity MTHFR
      genotypes was found in a group of ALL patients with relapses compared to healthy
      controls (p = 0.022) and ALL cases without relapse (p = 0.027). Mutations in the
      MTHFR gene decrease the onset risk of ALL with relapse in the setting of no
      folate supplementation in pregnancy, but not of relapse-free ALL.

PMID- 19178945
TI  - Emotional abuse in a sample of multiply maltreated, urban young adolescents:
      issues of definition and identification.
AB  - OBJECTIVE: The main purpose of this paper is to use the Brassard and Donovan
      [Brassard, M. R. & Donovan, K. L. (2006). Defining psychological maltreatment. In
      M. M. Freerick, J. F. Knutson, P. K. Trickett, & S. M. Flanzer (Eds.), Child
      abuse and neglect: Definitions, classifications, and a framework for research
      (pp. 151-197). Baltimore, MD: Paul H. Brookers Publishing Co., Inc.] framework to
      examine and describe the nature of emotional abuse experienced by a sample of
      urban, ethnically diverse male and female youth (N=303) identified as maltreated
      by a very large public child welfare agency. METHODS: Case record abstraction was
      conducted on the DCFS records of these maltreated youth using the Maltreatment
      Case Record Abstraction Instrument (MCRAI) which was based on the work of Barnett
      et al. [Barnett, D., Manly, J. T., & Cicchetti, D. (1993). Defining child
      maltreatment: The interface between policy and research. In D. Cicchetti & S. L.
      Toth (Eds.), Advances in applied developmental psychology: Child abuse, child
      development and social policy (pp. 7-73). Norwood, NJ: Ablex Publishing Corp.] as
      modified by English and LONGSCAN [English, D. J., & the LONGSCAN Investigators.
      (1997). Modified maltreatment classification system (MMCS). Retrieved from
      http://www.iprc.unc.edu/longscan/]. Fifteen items of parental behavior deemed
      emotionally abusive were coded and organized into four subtypes of emotional
      abuse (spurning, terrorizing, isolating, exploiting/corrupting) using the
      Brassard and Donovan (2006) framework. RESULTS: Using this coding system, almost
      50% of the sample were found to have experienced emotional abuse in contrast to
      9% identified at the time of referral by DCFS. Most of the emotionally abused
      youth also experienced physical abuse (63%) and/or neglect (76%) as well. The
      most frequent subtype of emotional abuse experienced was terrorizing. Most youth
      experienced more than one subtype. CONCLUSIONS: Emotional abuse, while frequent,
      was seldom the focus of the child protection services investigation. The nature
      of this abuse was not minor, but rather likely to be dangerous to the mental
      health and well-being of these children. Further more emotional abuse, in this
      sample of young adolescents, at least, was likely to be accompanied by other
      forms of maltreatment, especially physical abuse and/or neglect. These findings
      have important implications for practice and the direction of future research.
      PRACTICE IMPLICATIONS: All those who interact with child welfare clients must
      recognize the prevalence of emotional abuse in maltreated children so that
      appropriate interventions are instituted. Screening for emotional abuse should be
      part of all intake referrals and when confirmed should be noted in official
      records. When children are placed, foster parents (both kin and non-kin) need
      training on the prevalence and consequences of emotional abuse, and strategies to
      help their foster children recover from the aftermath. When children remain with
      maltreating parents, emotional abuse should be a focus of the interventions
      designed to help maltreating parents with more effective parenting strategies and
      also should be a focus of the interventions designed to help the child recover
      from the consequences of maltreatment.

PMID- 19178946
TI  - N-Hydroxyguanidines oxidation by a N3S copper-complex mimicking the reactivity of
      Dopamine beta-Hydroxylase.
AB  - N-Aryl-N'-hydroxyguanidines are compounds that display interesting
      pharmacological properties but their chemical reactivity remains poorly
      investigated. Some of these compounds are substrates for the heme-containing
      enzymes nitric-oxide synthases (NOS) and act as reducing co-substrates for the
      copper-containing enzyme Dopamine beta-Hydroxylase (DBH) [P. Slama, J.L. Boucher,
      M. Reglier, Biochem. Biophys. Res. Commun. 316 (2004) 1081-1087]. DBH catalyses
      the hydroxylation of the important neurotransmitter dopamine into norepinephrine
      in the presence of both molecular oxygen and a reducing co-substrate. Although
      many molecules have been used as co-substrates for DBH, their interaction at the
      active site of DBH and their role in mechanism are not clearly characterized. In
      the present paper, we have used a water-soluble copper-N(3)S complex that mimics
      the Cu(B) site of DBH, and aromatic N-hydroxyguanidines as reducers to address
      this question. N-Aryl-N'-hydroxyguanidines readily reduced copper(II) to Cu(I)
      and were oxidized into a nitrosoamidine as previously observed in reactions
      performed with purified DBH. These data describe for the first time the
      reactivity of N-aryl-N'-hydroxyguanidines with a water-soluble copper(II) complex
      and help to understand the interaction of co-substrates with copper at the active
      site of DBH.

PMID- 19178948
TI  - Efficacy of high frequency (rapid) suprathreshold repetitive transcranial
      magnetic stimulation of right prefrontal cortex in bipolar mania: a randomized
      sham controlled study.
AB  - OBJECTIVE: To examine the efficacy of adjunctive right prefrontal high-frequency
      suprathreshold rTMS treatment in bipolar affective disorder, mania patients as
      compared to sham stimulation. METHOD: 41 right handed bipolar mania patients were
      randomized to receive daily sessions of active or sham rTMS (20 Hz, 110% of MT,
      20 trains, 10 s intertrain interval) over the right dorsolateral prefrontal
      cortex for 10 days. Mania was rated using Young Mania Rating Scale (YMRS) and
      Clinical Global Impression (CGI) at baseline, and after 5th and 10th rTMS.
      RESULT: For YMRS scores, repeated measures ANOVA showed a significant effect of
      treatment over time as shown by interaction effect (F=12.95, df=1.51/58.94,
      p<0.001, Greenhouse-Geisser corrected). For CGI-S, repeated measures ANOVA showed
      a significant interaction effect of treatment over time (F=5.34, df=1.36/53.01,
      p=0.016, Greenhouse-Geisser corrected). CONCLUSION: High-frequency supra
      threshold right prefrontal rTMS in bipolar, mania patients was well tolerated and
      found to be effective as add-on to standard pharmacotherapy.

PMID- 19178947
TI  - Mechanical measurement of infant activity: a cautionary note.
AB  - Activity level in childhood has long been of interest to researchers in
      psychology, personality, and pediatrics. With the current epidemic in child
      obesity, even greater attention is being paid to physical activity and its role
      in preventing excess weight gain. Activity can be rated by observers as well as
      recorded more objectively by mechanical devices, however, some research suggests
      that estimates from these two sources do not always correlate. Via a
      demonstration with a human infant and a doll, the present report suggests that
      for younger infants at least, much of their measured activity may be confounded
      by their caregivers' movements.

PMID- 19178949
TI  - Persistence of mental health problems and needs in a college student population.
AB  - BACKGROUND: Cross-sectional studies indicate a high prevalence of mental health
      problems among college students, but there are fewer longitudinal data on these
      problems and related help-seeking behavior. METHODS: We conducted a baseline web
      based survey of students attending a large public university in fall 2005 and a
      two-year follow-up survey in fall 2007. We used brief screening instruments to
      measure symptoms of mental disorders (anxiety, depression, eating disorders), as
      well as self-injury and suicidal ideation. We estimated the persistence of these
      mental health problems between the two time points, and determined to what extent
      students with mental health problems perceived a need for or used mental health
      services (medication or therapy). We conducted logistic regression analyses
      examining how baseline predictors were associated with mental health and help
      seeking two years later. RESULTS: Over half of students suffered from at least
      one mental health problem at baseline or follow-up. Among students with at least
      one mental health problem at baseline, 60% had at least one mental health problem
      two years later. Among students with a mental health problem at both time points,
      fewer than half received treatment between those time points. LIMITATIONS: Mental
      health problems are based on self-report to brief screens, and the sample is from
      a single university. CONCLUSIONS: These findings indicate that mental disorders
      are prevalent and persistent in a student population. While the majority of
      students with probable disorders are aware of the need for treatment, most of
      these students do not receive treatment, even over a two-year period.

PMID- 19178950
TI  - Chicken heterophil extracellular traps (HETs): novel defense mechanism of chicken
      heterophils.
AB  - Recent findings in mammals and fish have revealed that neutrophil nuclear
      material associated with cytoplasmic granular content is released in the form of
      neutrophil extracellular traps (NETs) that can trap and kill invading
      microorganisms in vitro and in vivo. To determine if a similar mechanism is
      present in chicken heterophils, hydrogen peroxide (H(2)O(2)) and phorbol
      myristate acetate (PMA) were used for stimulation of blood-derived heterophils.
      Stimulated heterophils produced structures that were characterized using
      immunocytochemistry and confocal microscopy as heterophil extracellular traps
      (HETs). Released HETs contained DNA, histone-DNA complex and elastase from
      heterophil cytoplasmic granules. HETs released from chicken heterophils are
      structurally similar to NETs found in mammalian and fish neutrophils.
      Extracellular DNA released from heterophils was quantified by Picogreen assay.
      Stimulation with PMA or H(2)O(2) significantly increased the HET-DNA release
      index in vitro compared to non-stimulated heterophils (1.11+/-0.04 and 1.55+/
      0.10, respectively), and H(2)O(2) stimulation induced significantly higher HET
      DNA release than PMA (P<0.001). Thus, HETs are now characterized as an important
      heterophil-mediated defense mechanism in chickens.

PMID- 19178951
TI  - Vaccination of calves with Mycobacteria bovis Bacilli Calmete Guerin (BCG)
      induced rapid increase in the proportion of peripheral blood gammadelta T cells.
AB  - Changes in the proportion of peripheral blood T cell subsets after subcutaneous
      inoculation of cattle with Mycobacterium bovis Bacille Calmette-Guerin (BCG) were
      studied. Calves were injected with approximately 8 x 10(6) BCG bacillus and blood
      samples collected at weekly intervals for flow-cytometric analyses to determine
      the proportion of CD4+, CD8+ and gammadelta T cells. In addition, whole blood
      samples were stimulated in vitro with M. bovis purified protein derivative (PPD)
      and the secreted IFN-gamma quantified by ELISA. Results showed cellular and
      cytokine changes which could be categorized into three phases. The first phase
      occurred within the first 2 weeks after vaccination involving an increase in
      proportion of WC1+ gammadelta T cells and a concomitant increase in the secretion
      of IFN-gamma. These two responses peaked at 2 weeks and waned thereafter. The
      second phase involved an increase in the CD4/CD8 ratio as a result of an increase
      in the proportion of CD4+ T cells between 4 and 6 weeks. The third phase involved
      a decrease in the CD4/CD8 ratio due to an increase in the proportion of CD8+ T
      cells between 8 and 10 weeks. Surprisingly, the IFN-gamma response was associated
      with changes in the gammadelta rather than the CD4+ or CD8+ T cells, suggesting
      that this cytokine was secreted by gammadelta-T cells. These results are
      consistent with the reported ability of gammadelta T cells to act rapidly and
      bridging the innate and classically adaptive immune responses.

PMID- 19178952
TI  - Avian follicular and interdigitating dendritic cells: isolation and morphologic,
      phenotypic, and functional analyses.
AB  - An antiserum against Eimeria tenella sporozoites was used to localize and isolate
      Ag-binding cells in intestinal cecal tonsils of parasite-infected chickens. Based
      on their tissue localization, ultrastructural features, and expression of surface
      markers, two subpopulations of cells were isolated, CD45(+) interdigitating
      dendritic cells (IDCs) and CD45(-) follicular dendritic cells (FDCs). IDCs
      expressed MHC class I, MHC class II, and selectin, induced the proliferation of
      allogeneic naive CD4(+) T cells, and increased the secretion of IFN-gamma by
      autologous T cells. FDCs expressed surface IgG, IgM, ICAM-1, and VCAM-1,
      stimulated the proliferation of LPS-treated allogeneic B cells, and augmented the
      secretion of IgG by LPS-treated autologous B cells. Final cell yields were 6 x
      10(5) to 8 x 10(5) cells per chicken with >95% purity. In summary, this
      combination of methods using Abs against E. tenella and CD45 made it possible for
      the first time to obtain a highly enriched IDCs and FDCs which are functionally
      active in chickens. This novel method will enable the detailed biochemical and
      immunological characterizations of avian dendritic cells and facilitate the
      investigation of their role in initiating immune response in normal and disease
      states.

PMID- 19178953
TI  - Response of mucosal and systemic sIgM-positive cells in turbot (Scophthalmus
      maximus L.) immunization with Edwardsiella tarda.
AB  - Indirect fluorescence analyze technology (IFAT) and fluorescence-activated cell
      sorter (FACS) analysis were used to detect surface IgM positive cells (sIgM+
      cells) in lymphoid tissues of unvaccinated turbots and vaccinated ones with
      inactivated Edwardsiella tarda. The results were as follows: (1) The percentage
      of sIgM+ cells respectively was 0+/-0.00% of skin, 1.58+/-0.40% of gills, 17.05+/
      0.39% of peripheral blood (PBL), 21.06+/-1.79% of kidney in unvaccinated healthy
      turbots (average length: 7.12+/-0.5 cm; average height: 3.8+/-0.2 cm). (2) After
      direct immersion (d.i.), the response of sIgM+ cells was produced at first in the
      gills and thereafter in the kidney and PBL, and a significant increase of the
      number of sIgM+ cells was found in gills. (3) After immunization via
      intraperitoneal injection (i.p.), the response of sIgM+ cells was produced
      simultaneously in the gills, kidney and PBL after i.p., and a significant
      increase of the number of sIgM+ cells was found in PBL and kidney instead of in
      gills. These results strongly supported the different immunological role of
      gills, PBL and kidney upon the different administration routes, and the presence
      of two compartmental models for immune response in turbot.

PMID- 19178954
TI  - Fok-I vitamin D receptor gene polymorphism (rs10735810) and vitamin D metabolism
      in multiple sclerosis.
AB  - Multiple sclerosis (MS) has been associated with low levels of 25-hydroxyvitamin
      D (25(OH)D). Several genetic polymorphisms of the vitamin D receptor gene (VDRG),
      of whom Fok-I (rs10735810) has functional consequences for receptor protein
      structure and the immune system, have been studied in relation to MS with
      variable results. The purpose of our study was to assess an association of the
      Fok-I VDRG polymorphism with MS, and to further unravel the interaction of this
      polymorphism with vitamin D metabolism. Therefore, we genotyped 212 MS patients
      and 289 healthy controls for the Fok-I polymorphism and determined levels of the
      vitamin D metabolites 25(OH)D and 1,25(OH)(2)D. No association of the Fok-I VDRG
      polymorphism with MS was found. The F-allele was associated with lower winter and
      summer serum 25(OH)D levels in our MS patients, and with lower 25(OH)D levels in
      healthy controls. Remarkably, the F-allele corresponded with higher 1,25(OH)(2)D
      levels in MS patients. In all groups, carriers of the F-allele had higher
      1,25(OH)(2)D/ 25(OH)D-ratios compared to their f-allele counterparts. In
      conclusion, we demonstrated the importance of the Fok-I VDRG polymorphism for
      vitamin D metabolism. This should be taken into account in association and
      ultimately intervention studies on vitamin D and MS.

PMID- 19178956
TI  - Functional assessment and health-related quality of life (HRQOL) of elderly
      patients on the basis of the functional assessment of chronic illness therapy
      (FACIT)-F questionnaire.
AB  - Elderly patients represent a significant part of all the patients in various
      hospital wards. They also suffer from many diseases. Maintenance of their
      everyday independence, treatment, rehabilitation and improvement of their HRQOL
      is the main goal of geriatric care in the world, and also in Poland. Performing a
      comprehensive geriatric assessment for each elderly patient to identify their
      needs and problems is a standard procedure. The goal of this research was a
      functional assessment of the influence of social and clinical factors on HRQOL in
      elderly people. The aim of the study was to assess the influence of social and
      clinical factors on the functional state and HRQOL in elderly people. The study
      group was recruited among hospitalized patients in the Department and Clinic of
      Geriatrics, 64 women and 60 men, for a total of 124 people. The mean age of the
      study group was 72.1 years. The research was carried out using a diagnostic poll
      method with the application of FACIT-F questionnaire. The results of FACIT-F for
      the study group were running at an average level and were dependent on age,
      marital status, education level and duration of the illness. Correlations were
      found between the FACIT-F results and the following expectations of the patients:
      treatment, rehabilitation and information given about treatment, alleviating
      pain, referral to social care, organizing home care. Results of FACIT-F were
      dependent on activities of daily living (ADL) scores in the study group.

PMID- 19178955
TI  - Nothing can be coincidence: synaptic inhibition and plasticity in the cerebellar
      nuclei.
AB  - Many cerebellar neurons fire spontaneously, generating 10-100 action potentials
      per second even without synaptic input. This high basal activity correlates with
      information-coding mechanisms that differ from those of cells that are quiescent
      until excited synaptically. For example, in the deep cerebellar nuclei, Hebbian
      patterns of coincident synaptic excitation and postsynaptic firing fail to induce
      long-term increases in the strength of excitatory inputs. Instead, excitatory
      synaptic currents are potentiated by combinations of inhibition and excitation
      that resemble the activity of Purkinje and mossy fiber afferents that is
      predicted to occur during cerebellar associative learning tasks. Such results
      indicate that circuits with intrinsically active neurons have rules for
      information transfer and storage that distinguish them from other brain regions.

PMID- 19178957
TI  - Congenital left ventricular subaortic aneurysm in an asymptomatic child.
AB  - A newborn was referred to our department, due to the presence of a cardiac
      murmur. Echocardiographic study showed a small membranous ventricular septal
      defect and a yuxta-aortic mass. In the follow-up, patient remained asymptomatic,
      ventricular septal defect closed, and yuxta-aortic mass increase in size with
      somatic growth. A transesophageal echocardiography was carried out, showing a
      fibrotic and dyskinetic left ventricular subaortic aneurysm of 19*18 mm. Given
      that the patient remained asymptomatic, a conservative approach was adopted.
      Congenital left ventricular subaortic aneurysm is an infrequent entity, and
      rupture, endocarditis, coronary compression, thromboembolism, arrhythmias and
      aortic insufficiency are some of its complications, but, as in our patient, if
      aneurysm is not associated with complications, patient is asymptomatic, and
      aneurysm growth is not very important, a conservative approach can be adopted,
      with a close surveillance.

PMID- 19178958
TI  - Partitioning total heart rate variability.

PMID- 19178959
TI  - Long-term outcome of transcatheter patent foramen ovale closure in patients with
      paradoxical embolism.
AB  - BACKGROUND: Optimal management of patients with PFO and paradoxical embolic
      events is still debated. Moreover, data from long-term studies on large patient
      populations are lacking. Aim of the study is to assess immediate and long-term
      clinical outcome of patients with PFO and paradoxical thrombo-embolic events
      submitted to transcatheter PFO closure. METHODS: Only patients with PFO-related
      transient ischemic attack or stroke underwent PFO closure. Patients were
      evaluated clinically and echocardiographically at 1, 6 and 12 months after the
      procedure and yearly thereafter. Primary endpoints were death, recurrent stroke
      or TIA. Residual right-to left shunt (RLS) was monitored by transthoracic
      echocardiography (TTE) or transcranial Doppler (TCD) at 6 months'follow-up.
      RESULTS: 202 consecutive patients underwent percutaneous PFO closure for
      secondary prevention of TE. Device migration was observed in one patient 24 h
      after the procedure. No cases of procedure-related death or stroke occurred
      during a median follow-up of 3+/-1.3 years. Three recurrent TIAs were observed
      within the first 6 months of follow-up. The cumulative estimated probability of
      recurrent TE-free survival rate after PFO closure was 99% in patients <or=55
      years, 84% in patients >55 years (p<0.05) and 94% and 100% in patients with PFO,
      with or without atrial septal aneurysm (ASA), respectively (p<0.05). Of the 188
      (93%) patients submitted to TTE or TCD at 6 months' follow-up, 8 (4%) presented a
      small RLS. CONCLUSION: Transcatheter PFO closure is associated with low incidence
      of in-hospital complications and low frequency of recurrent TE at long-term
      follow-up.

PMID- 19178960
TI  - Picrorhiza scrophulariiflora improves accelerated atherosclerosis through
      inhibition of redox-sensitive inflammation.
AB  - BACKGROUND: Accumulation of advanced glycation end products (AGEs) or advanced
      oxidation protein products (AOPPs) has been identified as a risk factor for
      accelerated atherosclerosis seen in diabetes and chronic kidney disease. However,
      little is known about the intervention for atherogenesis associated with these
      oxidized proteins. The rhizome of Picrorhiza scrophulariiflora (PS) has long been
      used to treat inflammatory diseases as a traditional medication. The study was
      performed to test the hypothesis that ethanol extraction of PS (EPS) may improve
      AGEs- or AOPPs-induced accelerated atherosclerosis in vivo. METHODS AND RESULTS:
      Hypercholesterolemic or normal rabbits were randomly assigned to 8 groups treated
      with intravenous injection of AGEs- or AOPPs-modified rabbit serum albumin (AGEs
      RSA or AOPPs-RSA), unmodified RSA or vehicle in the presence or absence of EPS
      (10 mg/kg/2 days) gavage for 10 weeks. Compared with hypercholesterolemic rabbits
      without EPS treatment, EPS administration significantly decreased the aortic
      plaque volume and oxidized low density lipoprotein (Ox-LDL) deposition in
      hypercholesterolemic animals. This was accompanied by significant histological
      improvement including decrease of intimal and smooth muscle cell proliferation
      and macrophage influx in affected areas. EPS administration almost completely
      abolished the accelerated atherosclerosis induced by chronic treatment of AGEs-
      or AOPPs-RSA in both hypercholesterolemic and normal rabbits. EPS administration
      significantly restored the AGEs- or AOPPs-induced redox imbalance and
      inflammation, evidenced by decrease of plasma Ox-LDL, thiobarbituric acid
      reactive substances and TNF-alpha, and increase of glutathione peroxidase
      activity. CONCLUSION: These data suggested that EPS may improve atherosclerosis,
      particularly that induced by AGEs or AOPPs, through inhibition of redox-sensitive
      inflammation.

PMID- 19178961
TI  - Direct comparison of the short-term clinical performance of Z Guidant and Taxus
      stents.
AB  - The recent introduction of drug-eluting stents in angioplasty of atherosclerotic
      blood vessels has significantly reduced the risks of in-stent restenosis (ISR)
      [1]. Indeed, it is known that in conventional stents ISR takes place in over 20%
      of the cases and up to 60% when implanted in diabetic patients. Conversely,
      clinical trials have shown that drug-eluting stents have significantly reduced
      ISR. Among the drug-eluting stents available on the market, Taxus stents (Tax,
      Boston Scientific, USA) are among the most used devices [2]. Tax are stainless
      steel stents coated with Translute, a poly(styrene-b-isobutylene-b-styrene)
      polymer (PSIBS) eluting Placlitaxel, an anti-mitotic drug. Clinical trials on
      this type of drug-eluting stents have shown an incidence of restenosis of
      approximately 4%. The majority of these trials were randomized studies where
      conventional stents and drug-eluting devices have been implanted in separate
      patients' cohorts. Such a randomized design, although fundamental to collect
      statistically-relevant data, does not allow a direct histological comparison of
      different stent types when implanted in the same patient and do not show the
      individual susceptibility to the host response especially at short-term
      implantation times. Here, an interesting case study is presented where two chrome
      cobalt stents (Z Guidant, ZG, Guidant Corp.) and a Tax have been simultaneously
      implanted in the same patient in three separate coronary arteries, retrieved
      after only 8 weeks and histologically analysed.

PMID- 19178962
TI  - The spectrum of inflammatory myopericardial diseases.

PMID- 19178963
TI  - Serial snapshot electrocardiograms and continuous 12-lead ST-segment
      electrocardiographic monitoring for the prediction of intravenous thrombolysis
      outcome in patients with ST-segment elevation myocardial infarction.

PMID- 19178964
TI  - C-reactive protein and left atrial appendage velocity are independent
      determinants of the risk of thrombogenesis in patients with atrial fibrillation.
AB  - BACKGROUND: The association between inflammatory status and thrombosis in
      patients with atrial fibrillation (AF) is unclear. We studied the correlation
      between inflammation and the risk of thrombogenesis in patients with AF and the
      relationship of inflammation with other factors associated with thrombotic risk.
      METHODS: We studied 150 consecutive patients (69 men, age 65+/-12 years) with
      persistent non-valvular AF who had transesophageal echocardiography prior to
      cardioversion. Patients underwent also measurements of high-sensitivity C
      reactive protein, fibrinogen, D-dimer, and hematocrit levels. RESULTS: Patients
      were divided into two groups according to the presence (n=52) or absence (n=98)
      of dense spontaneous echo contrast (SEC) in left atrium or left atrial appendage.
      The two groups were similar for age, sex, and major clinical risk factors.
      Patients with dense SEC had significantly larger left atrium diameter (p=0.007),
      lower left atrial appendage mean velocity (p<0.0001), and higher levels of C
      reactive protein (p=0.003), D-dimer (p=0.008), and fibrinogen (p=0.006). At
      multivariate analysis, only left atrial appendage velocity (odds ratio: 19.11;
      95% confidence interval 4.2-80.9) and C-reactive protein (odds ratio: 3.41; 95%
      confidence interval 1.2-9.8) were significantly associated with thrombus and/or
      dense SEC. However, there was no relationship between C-reactive protein levels
      and left atrial appendage velocity (p=0.24, r=-0.09). CONCLUSIONS: Our results
      show that left atrial appendage velocity and C-reactive protein are independently
      associated with the risk of thromboembolism in AF. Thus, blood stasis and
      inflammation appear to constitute two major distinct components of
      thrombogenesis.

PMID- 19178965
TI  - Effects of diabetes mellitus in patients with heart failure and chronic kidney
      disease: a propensity-matched study of multimorbidity in chronic heart failure.
AB  - BACKGROUND: Chronic kidney disease (CKD) and diabetes mellitus (DM) are common
      comorbidities in heart failure (HF) and each is associated with poor outcomes.
      However, the effects of multimorbidity related to having both CKD and DM compared
      to CKD alone have not been well studied in a propensity-matched population of
      chronic HF patients. METHODS: Of the 7788 ambulatory chronic HF patients in the
      Digitalis Investigation Group trial, 3527 had CKD, of whom 1095 had DM. Based on
      the absence or presence of DM, patients were categorized CKD-only and CKD-DM,
      respectively. Propensity scores for CKD-DM were calculated for each patient and
      were used to match 987 pairs of CKD-only and CKD-DM patients. Hazard ratios (HR)
      and 95% confidence intervals (CI) comparing CKD-DM patients with CKD-only
      patients were estimated using matched Cox regression models. RESULTS: All-cause
      mortality occurred in 47.0% (rate, 1783/10,000 person-years of follow-up) of CKD
      DM patients and 39.6% (rate, 1414/10,000 person-years) of CKD-only patients (HR
      when CKD-DM is compared with CKD-only, 1.25; 95%-CI, 1.07-1.46; p=0.006). All
      cause hospitalization occurred in 75.4% (rate, 5710/10,000 person-years) and
      67.8% (rate, 4213/10,000 person-years) of CKD-DM and CKD-only patients
      respectively (HR, 1.32; 95%-CI, 1.15-1.52; p<0.0001). Respective HR and 95%-CI
      for other outcomes were: cardiovascular mortality (1.27; 1.06-1.52; p=0.009), HF
      mortality (1.34; 1.04-1.72; p=0.025); cardiovascular hospitalization (1.29; 1.12
      1.49; p=0.001) and HF hospitalization (1.37; 1.16-1.63; p<0.0001). CONCLUSIONS:
      Compared with comorbidity due to CKD alone, multimorbidity with CKD and DM was
      associated with poor outcomes in chronic HF patients.

PMID- 19178966
TI  - Comparison between dairy cow disease incidence in data registered by farmers and
      in data from a disease-recording system based on veterinary reporting.
AB  - Sweden has a national disease-recording system based on veterinary reporting.
      From this system, all cattle-disease records are transferred to the dairy
      industry cattle database (DDD) where they are used for several purposes including
      research and dairy-health statistics. Our objective was to evaluate the
      completeness of this data source by comparing it with disease data registered by
      dairy farmers. The proportion of veterinary-treated disease events was estimated,
      by diagnosis. Disease incidence in the DDD was compared, by diagnosis and age,
      with disease data registered by the farmers. Comparison was made, by diagnosis,
      for (i) all disease events and (ii) those reported as veterinary-treated. Disease
      events, defined as "observed deviations in health, from the normal" were recorded
      by the farmers during January, April, July and October 2004. For the diagnoses
      calving problems, peripartum disorders, puerperal paresis and retained placenta,
      incidence proportions (IP) with 95% confidence intervals (CIs) were estimated.
      For all other disease problems, incidence rates (IR) were used. In total, 177
      farmers reported at least 1 month and 148 reported all 4 months. Fifty-four
      percent of all disease events in the farmers' data were reported as veterinary
      treated. For several of the most common diagnoses, the IRs and IPs for all events
      were significantly higher in farmers' data than in the DDD. Examples are, in
      cows: clinical mastitis, cough, gastro-intestinal disorders and lameness in hoof
      and limb; and in young stock: cough and gastro-intestinal disorders. For
      veterinary-treated events only, significant differences with higher IR in the
      farmers' data were found in young stock for sporadic cough and sporadic gastro
      intestinal disorders. The diagnosis "other disorders" had significantly more
      events in the DDD than in farmers' data, i.e. veterinarians tended to choose more
      unspecific diagnoses than the farmers. This result indicates that the true
      completeness is likely to be higher than our estimate. We conclude that for the
      time period studied there was differential under-reporting associated with the
      diagnosis, the age of the animal and whether the herd was served by a state
      employed or private veterinarian.

PMID- 19178967
TI  - Simulation of foot-and-mouth disease spread within an integrated livestock system
      in Texas, USA.
AB  - We used a simulation study to assess the impact of an incursion of foot-and-mouth
      disease (FMD) virus on the livestock industries in an 8-county area of the
      Panhandle region of Texas, USA. The study was conducted in a high-density
      livestock area, with an estimated number of cattle on-feed of approximately 1.8
      million. We modified an existing stochastic, spatial simulation model to simulate
      64 scenarios for planning and decision-making. Our scenarios simulated four
      different herd types for the index herd (company feedlot, backgrounder feedlot,
      large beef, backyard) and variations in three mitigation strategies (time-of
      detection, vaccine availability, and surveillance during disease control). Under
      our assumptions about availability of resources to manage an outbreak, median
      epidemic lengths in the scenarios with commercial feedlot, backgrounder feedlot,
      large beef and backyard index herd types ranged from 28 to 52, 19 to 39, 18 to
      32, and 18 to 36 days, respectively, and the average number of herds depopulated
      ranged from 4 to 101, 2 to 29, 1 to 15 and 1 to 18, respectively. Early detection
      of FMD in the index herd had the largest impact on reducing ( approximately 13-21
      days) the length of epidemics and the number of herds ( approximately 5-34)
      depopulated. Although most predicted epidemics lasted only approximately 1-2
      months, and <100 herds needed to be depopulated, large outbreaks lasting
      approximately 8-9 months with up to 230 herds depopulated might occur.

PMID- 19178968
TI  - Back-calculation method shows that within-flock transmission of highly pathogenic
      avian influenza (H7N7) virus in the Netherlands is not influenced by housing risk
      factors.
AB  - To optimize control of an avian influenza outbreak knowledge of within-flock
      transmission is needed. This study used field data to estimate the transmission
      rate parameter (beta) and the influence of risk factors on within-flock
      transmission of highly pathogenic avian influenza (HPAI) H7N7 virus in the 2003
      epidemic in The Netherlands. The estimation is based on back-calculation of daily
      mortality data to fit a susceptible-infectious-dead format, and these data were
      analysed with a generalized linear model. This back-calculation method took into
      account the uncertainty of the length of the latent period, the survival of an
      infection by some birds and the influence of farm characteristics. After
      analysing the fit of the different databases created by back-calculation, it
      could be concluded that an absence of the latency period provided the best fit.
      The transmission rate parameter (beta) from these field data was estimated at
      4.50 per infectious chicken per day (95% CI: 2.68-7.57), which was lower than
      what was reported from experimental data. In contrast to general belief, none of
      the studied risk factors (housing system, flock size, species, age of the birds
      in weeks and date of depopulation) had significant influence on the estimated
      beta.

PMID- 19178969
TI  - The role of backyard poultry flocks in the epidemic of highly pathogenic avian
      influenza virus (H7N7) in the Netherlands in 2003.
AB  - In recent years, outbreaks of highly pathogenic avian influenza (HPAI) viruses
      have caused the death of millions of poultry and of more than 200 humans
      worldwide. A proper understanding of the transmission dynamics and risk factors
      for epidemic spread of these viruses is key to devising effective control
      strategies. The aim of this study was to quantify the epidemiological
      contributions of backyard flocks using data from the H7N7 HPAI epidemic in the
      Netherlands in 2003. A dataset was constructed in which flocks in the affected
      area were classified as susceptible (S), infected but not yet infectious (E),
      infectious (I), and removed (R). The analyses were based on a two-type SEIR
      epidemic model, with the two types representing commercial poultry farms and
      backyard poultry flocks. The analyses were aimed at estimation of the
      susceptibility (g) and infectiousness (f) of backyard flocks relative to
      commercial farms. The results show that backyard flocks were considerably less
      susceptible to infection than commercial farms (g = 0.014; 95%CI = 0.0071-0.023),
      while estimates of the relative infectiousness of backyard flocks varied widely
      (0 < or = f < or =5). Our results indicate that, from an epidemiological
      perspective, backyard flocks played a marginal role in the outbreak of highly
      pathogenic avian influenza in the Netherlands in 2003.

PMID- 19178970
TI  - Blood donation and the nature of altruism.
AB  - Approximately 10% of people have O-negative blood. Because it can be transfused
      into almost anyone, hospitals particularly value such blood. We use this fact,
      together with the assumption that blood types are exogenously assigned by nature,
      to design an empirical inquiry into altruism. We also investigate the timing of
      donations, especially focussing on the behaviour of new and established donors.
      We show that O-negative blood donors donate no more often than other people. Thus
      individuals apparently do not exhibit pure altruism. We speculate that instead
      blood donors may be driven by a broad notion of duty rather than by a far
      sighted, rational unselfishness.

PMID- 19178971
TI  - Are mature smokers misinformed?
AB  - While there are many reasons to continue to smoke in spite of its consequences
      for health, the concern that many smoke because they misperceive the risks of
      smoking remains a focus of public discussion and motivates tobacco control
      policies and litigation. In this paper we investigate the relative accuracy of
      mature smokers' risk perceptions about future survival, and a range of
      morbidities and disabilities. Using data from the survey on smoking (SOS)
      conducted for this research, we compare subjective beliefs elicited from the SOS
      with corresponding individual-specific objective probabilities estimated from the
      health and retirement study. Overall, consumers in the age group studied, 50-70,
      are not overly optimistic in their perceptions of health risk. If anything,
      smokers tend to be relatively pessimistic about these risks. The finding that
      smokers are either well informed or pessimistic regarding a broad range of health
      risks suggests that these beliefs are not pivotal in the decision to continue
      smoking. Although statements by the tobacco companies may have been misleading
      and thus encouraged some to start smoking, we find no evidence that systematic
      misinformation about the health consequences of smoking inhibits quitting.

PMID- 19178972
TI  - Accelerated partial breast irradiation trials: diversity in rationale and design.
AB  - Seven randomised trials are currently testing accelerated partial breast
      irradiation against whole breast radiotherapy after breast conservation surgery.
      The trials are varied in the techniques used to deliver partial breast
      radiotherapy, reflecting the range of opportunities offered by advanced
      brachytherapy and teletherapy modalities. Dose schedules also vary between
      trials, but the most important point of difference between them reflects
      alternative concepts of clinical and planning target volumes. These are based
      mainly on the spatial pattern of relapse in retrospective and prospective
      studies, which report the majority of first local relapses close to the primary
      tumour site, and on the assumption that radiotherapy does not prevent the
      development of new primary tumours developing elsewhere in the breast. However,
      the pattern of ipsilateral breast tumour relapse is not accurately defined in the
      clinical literature and does not correspond closely to pathological findings. In
      addition, published data are consistent with a significant reduction in the rate
      of other quadrant relapse after whole breast radiotherapy. Regardless of the
      biological model of local tumour relapse and responsiveness to radiation, the
      ongoing trials will generate level I evidence for or against accelerated partial
      breast irradiation, provided patients are followed up long enough before the
      first reporting of results.

PMID- 19178973
TI  - Inhibition of leukotriene B4 production in murine macrophages by lactic acid
      bacteria.
AB  - Leukotriene B(4) (LTB(4)) is a lipid mediator associated with innate immune
      function. LTB(4) is produced mainly by polymorphonuclear leukocytes and
      macrophages and plays important roles in host defense. However, LTB(4) is also
      associated with inflammation, and excessive production of LTB(4) can result in
      inflammation, allergic reactions, and carcinogenesis. Regulation of excessive
      LTB(4) production may therefore assist in controlling these conditions. In this
      study, we investigated the capacity of 7 strains of lactic acid bacteria to
      inhibit LTB(4) production by the murine macrophage cell line J774.1. All strains
      tested inhibited calcium ionophore (A23187)-stimulated LTB(4) production in
      macrophages, but to varying extents. Lactobacillus helveticus Bc-10 exhibited the
      highest level of inhibitory activity. The inhibitory activity of strain Bc-10 was
      sustained after heat-killing and was observed in the intracellular cell-free
      extract prepared from this strain. This is the first report that intact lactic
      acid bacteria and their isolated cellular components can directly inhibit LTB(4)
      production by macrophages, and provides a useful method to screen the inhibitory
      activity of lactic acid bacteria. This study also highlights the potential of the
      strain Bc-10 as a treatment option for the regulation of LTB(4) production in
      vivo.

PMID- 19178974
TI  - Analysis of foodborne outbreak data reported internationally for source
      attribution.
AB  - Analysis of foodborne outbreak data is one approach to estimate the proportion of
      human cases of specific enteric diseases attributable to a specific food item
      (food attribution). Although we recognize that for a variety of reasons reported
      outbreaks represent only a small portion of all actual outbreaks, using outbreak
      data for food attribution is the only methodological approach where,
      theoretically, there is an actual direct link between the pathogen, its source
      and each infected person. The purpose of this study was to explore the usefulness
      of foodborne outbreak data extracted from publicly available international
      electronic reports and publications to provide estimates of food attribution, to
      derive and compare these estimates between regions, while improving the
      understanding of the pathogen/food vehicle combination. Electronic reports and
      publications of foodborne outbreaks that occurred globally since the 1980s were
      systematically scanned and their data were extracted and compiled in a database.
      A system of food categorization was developed and food vehicles assigned
      accordingly. The association between the aetiology and the food source was
      statistically described for outbreaks with both reported aetiology and
      incriminated food vehicle. Differences in associations between Australia and New
      Zealand, Canada, the European Union (EU) and the United States (US) were explored
      using multiple correspondence analysis and were formally tested between the EU
      and the US for selected pathogens and food sources. As a result, the food and
      aetiology cross tabulation of 4093 foodborne outbreaks that occurred globally
      between 1988 and 2007 is presented and discussed. For a few aetiologies and some
      foods the association is very specific. The lack of a specific association
      between the other foods and aetiologies highlights the potential roles of cross
      contamination, environmental contamination and the role of the infected
      foodhandler along the food chain from farm to fork. Detailed analysis of the four
      regions highlighted some specific associations: Salmonella Enteritidis outbreaks
      occurred relatively often in the EU states with eggs as the most common source;
      Campylobacter associated outbreaks were mainly related to poultry products in the
      EU and to dairy products in the US; there was an association between Escherichia
      coli outbreaks and beef in Canada; and while Salmonella Typhiumurium outbreaks
      were relatively common in Australia and New Zealand, across all regions,
      Salmonella was associated with a variety of food groups. The value and
      limitations of the study are discussed, as well as the extrapolation of the food
      attribution estimates beyond their outbreak context.

PMID- 19178975
TI  - Toward quality improvement of cardiovascular surgery in Japan: an estimation of
      regionalization effects from a nationwide survey.
AB  - INTRODUCTION: In this study, we estimate the effects of regionalization for
      cardiovascular surgery in Japan, accounting for both its advantages and
      disadvantages. METHODS: This study includes 209,221 procedures from nearly 572
      hospitals that conducted cardiovascular surgery in Japan between 2001 and 2004.
      For the regionalization parameter, hospital surgical volume was divided into four
      categories: under 10, 10-24, 25-49, and 50-74 average cardiovascular surgeries
      per year. The effects of regionalization on the 30-day patient mortality rate and
      an additional travel distance for patients were examined. RESULTS: The 30-day
      mortality rate for cardiovascular surgery was 4.62% without regionalization.
      After regionalization, the estimated rate was 4.40% for annual case volumes under
      10, 4.28% for volumes 10-24, 3.78% for volumes 25-49, and 3.12% for volumes 50
      74. The average annual number of patients who must travel at least an extra 30 km
      after regionalization are: 0.8 patients for case volumes under 10 (0.001% of
      total patients), 12.3 patients for volumes 10-24 (0.02% of total), 88.3 patients
      for volumes 25-49 (0.2% of total), and 179.3 patients for volumes 50-74 (0.3% of
      total). CONCLUSION: The results indicate that, after regionalization, the 30-day
      mortality rate did improve for hospitals with 25-49 and 50-74 annual surgeries.
      While increased travel times may be critical for patients requiring emergency
      surgery, the results suggest that low-volume hospitals get relatively few such
      cases. In many regions, improving the transportation system for emergency cases
      may be more effective than maintaining a low-volume.

PMID- 19178976
TI  - Casualized employment and turnover intention: home care workers in Ontario,
      Canada.
AB  - The purpose of this paper is to examine the associations between casualized
      employment and turnover intention in home care. Casualized employment refers to
      employment conditions of non-permanent contracts, part-time or casual hours,
      involuntary hours, on-call work, split shifts, pay per visit, and hourly pay with
      variable hours. Casualized employment also refers to perceived employment
      insecurity and labour market insecurity. Data are from a survey of 991 visiting
      nurses, therapists and home support workers in a medium-sized city in Ontario,
      Canada. Results show that, controlling for many other factors, casual hours and
      perceived employment insecurity and labour market insecurity are positively and
      on-call work is negatively associated with home care workers' turnover intention.
      Non-permanent contract, part-time hours, involuntary hours, split shifts, and non
      salaried pay are features of the market-modelled home care work environment and
      therefore may not be associated with turnover intention. Results provide evidence
      on the effects of casualized employment strategies on home care workers' turnover
      intention.

PMID- 19178977
TI  - Monitoring with a non-invasive bioluminescent in vivo imaging system of pleural
      metastasis of lung carcinoma.
AB  - OBJECTIVES: The prognosis of patients with malignant pleural effusion (MPE) is
      poor. An MPE model is necessary for developing new therapeutic strategies. We
      established a MPE model and investigated the therapeutic effects of the
      administration of serial doses of docetaxel on intrathoracic disseminated foci
      using an in vivo image system (IVIS). METHODS: First, mice without pleural
      metastasis of lung carcinoma were given a single injection of docetaxel
      (Taxotere) in the thoracic cavity. The average weight of each group was
      evaluated. Next, docetaxel was injected into the thoracic cavity of the mice once
      a week for 8 weeks. Again, the average weight of each group was evaluated.
      Finally, A549 lung cancer cells transfected with luciferase gene (A549-Luc) were
      injected into the intrapleural cavity of the mouse. When pleural metastasis was
      established, we started repeated intrapleural administration of docetaxel (once a
      week for 8 weeks). The average weight of each group and the survival period was
      evaluated. All bioluminescent data were collected and analysed with a Xenogen
      IVIS system. RESULTS: (1) Single administration study: The average weight of mice
      injected with 50mg/kg docetaxel dropped 10%. (2) Repeat administration study: In
      the group of mice injected with 25mg/kg or 50mg/kg docetaxel, the average weight
      dropped by 10%. (3) A549-Luc cells were injected into the thoracic cavity of the
      mice. Autopsies revealed disseminated foci in thoracic cavity 7 days or more
      after inoculation. After confirmation of tumor formation, repeated injections of
      docetaxel were administered. After 21 days, photon counts from the thoracic
      cavity of untreated mice increased. Repeated intrapleural administration of
      docetaxel prolonged survival when compared to the control group. CONCLUSIONS: (1)
      We established a MPE model. (2) IVIS facilitates faster and more accurate
      counting of disseminated foci in the pleura (as compared to the previous standard
      of measuring body weight changes) in a cancerous pleuritis model. (3) Repeated
      intrapleural administration of docetaxel is effective.

PMID- 19178978
TI  - A meta-analysis of TP53 codon 72 polymorphism and lung cancer risk: evidence from
      15,857 subjects.
AB  - The genetic polymorphism of TP53 codon 72 is thought to have significant effect
      on lung cancer risk, but the results are inconsistent. In this meta-analysis, we
      assessed 23 published studies involving 15,857 subjects of the association
      between TP53 codon 72 polymorphism and risk of lung cancer. For the homozygote
      Pro/Pro and Pro allele carriers (Pro/Pro+Pro/Arg), the ORs for all studies
      combined (7495 cases and 8362 controls) were 1.221 (95% CI=1.046-1.425; P=0.021
      for heterogeneity) and 1.148 (95% CI=1.040-1.266; P=0.008 for heterogeneity). In
      the stratified analysis by ethnicity, significantly increased risks were found in
      Asians (3254 cases and 3350 controls) for both the homozygote Pro/Pro (OR=1.395;
      95% CI=1.206-1.613; P=0.806 for heterogeneity) and the Pro allele carriers
      (OR=1.109; 95% CI=1.000-1.228; P=0.458 for heterogeneity). In Caucasians (3359
      cases and 3953 controls), significantly elevated risk was associated with Pro
      allele carriers (OR=1.180; 95% CI=1.029-1.353; P=0.073 for heterogeneity). In the
      subgroup analyses by pathological type, the ORs for the homozygote Pro/Pro and
      Pro allele carriers were 1.289 (95% CI=1.027-1.618; P=0.096 for heterogeneity)
      and 1.168 (95% CI=1.062-1.284; P=0.231 for heterogeneity) for lung adenocarcinoma
      (2724 cases and 6591 controls). When stratified by smoking status, the pooled OR
      was 1.440 (95% CI=1.078-1.923; P=0.042 for heterogeneity) for the Pro allele
      carriers among smokers (1480 cases and 1414 controls). Although some statistical
      bias could not be eliminated, this meta-analysis suggests that the Pro allele is
      a low-penetrant risk factor for developing lung cancer. Additionally, we found
      that this phenomenon was more prominent in subgroups such as in Asians and
      Caucasians, in lung adenocarcinoma, or in smokers.

PMID- 19178979
TI  - Unravelling the evolution of autumn colours: an interdisciplinary approach.
AB  - Leaf colour change is commonly observed in temperate deciduous forests in autumn.
      This is not simply a side effect of leaf senescence, and, in the past decade,
      several hypotheses have emerged to explain the evolution of autumn colours. Yet a
      lack of crosstalk between plant physiologists and evolutionary ecologists has
      resulted in slow progress, and so the adaptive value of this colour change
      remains a mystery. Here we provide an interdisciplinary summary of the current
      body of knowledge on autumn colours, and discuss unresolved issues and future
      avenues of research that might help reveal the evolutionary meaning of this
      spectacle of nature.

PMID- 19178980
TI  - Stochasticity in evolution.
AB  - The debate over the role of stochasticity is central in evolutionary biology,
      often summarised by whether or not evolution is predictable or repeatable. Here
      we distinguish three types of stochasticity: stochasticity of mutation and
      variation, of individual life histories and of environmental change. We then
      explain when stochasticity matters in evolution, distinguishing four broad
      situations: stochasticity contributes to maladaptation or limits adaptation; it
      drives evolution on flat fitness landscapes (evolutionary freedom); it might
      promote jumps from one fitness peak to another (evolutionary revolutions); and it
      might shape the selection pressures themselves. We show that stochasticity, by
      directly steering evolution, has become an essential ingredient of evolutionary
      theory beyond the classical Wright-Fisher or neutralist-selectionist debates.

PMID- 19178981
TI  - Something in the way you move: dispersal pathways affect invasion success.
AB  - Biological invasions are caused by human-mediated extra-range dispersal and,
      unlike natural extra-range dispersal, are often the result of multiple
      introductions from multiple sources to multiple locations. The processes and
      opportunities that result in propagules moving from one area to another can be
      used more broadly to differentiate all types of extra-range dispersal. By
      examining key properties of dispersal pathways (notably propagule pressure,
      genetic diversity and the potential for simultaneous movement of coevolved
      species), the establishment and evolutionary trajectories of extra-range
      dispersal can be better understood. Moreover, elucidation of the mechanistic
      properties of dispersal pathways is crucial for scientists and managers who wish
      to assist, minimise or prevent future movements of organisms.

PMID- 19178982
TI  - A multi-flowpath model for the interpretation of immiscible displacement
      experiments in heterogeneous soil columns.
AB  - This work focuses on the phenomenon of the immiscible two-phase flow of water and
      oil in saturated heterogeneous soil columns. The goal is to develop a fast and
      reliable method for quantifying soil heterogeneities for incorporation into the
      relevant capillary pressure and relative permeability functions. Such data are
      commonly used as input data in simulators of contaminant transport in the
      subsurface. Rate-controlled drainage experiments are performed on undisturbed
      soil columns and the transient response of the axial distribution of water
      saturation is determined from electrical measurements. The transient responses of
      the axial distribution of water saturation and total pressure drop are fitted
      with the multi-flowpath model (MFPM) where the pore space is regarded as a system
      of parallel paths of different permeability. The MFPM enables us to quantify soil
      heterogeneity at two scales: the micro-scale parameters describe on average the
      effects of pore network heterogeneities on the two-phase flow pattern; the macro
      scale parameters indicate the variability of permeability at the scale of
      interconnected pore networks. The capillary pressure curve is consistent with
      that measured with mercury intrusion porosimetry over the low pressure range. The
      oil relative permeability increases sharply at a very low oil saturation (<10(
      3)) and tends to a high end value. The water relative permeability decreases
      abruptly at a low oil saturation (~0.1), whereas the irreducible wetting phase
      saturation is quite high. The foregoing characteristics of the two-phase flow
      properties are associated with critical (preferential) flowpaths that comprise a
      very small percentage of the total pore volume, control the overall hydraulic
      conductivity, and are consistent with the very broad range of pore-length scales
      usually probed in soil porous matrix.

PMID- 19178983
TI  - Intertriginous pustular psoriasis.
AB  - We describe 6 patients who presented during infancy with erythematous papules or
      pustules localized to the neck and sometimes other intertriginous areas as well.
      Most of these infants were initially thought to have dermatitis or a bacterial or
      candidal infection. A biopsy specimen established the diagnosis of pustular
      psoriasis in 5 of the 6 cases. In 4 cases, the psoriasis became more widespread
      during the months to years after diagnosis. Treatment included topical therapy in
      all cases and systemic therapy in 3 cases. Two cases have remained particularly
      recalcitrant. Pustular psoriasis must be considered in the differential diagnosis
      of an intertriginous papulopustular eruption in an infant. Pustular psoriasis
      presenting in the intertriginous areas, and particularly the neck, seems specific
      to infants and may portend progressive extension to widespread involvement. A
      limitation is that this was a retrospective case series.

PMID- 19178984
TI  - Neuroselective transcutaneous electrical stimulation reveals neuronal
      sensitization in atopic dermatitis.
AB  - BACKGROUND: The neuroselective transcutaneous electrical stimulator (NTES) can
      provoke itch and/or pain by the application of a 5-Hz alternating current.
      OBJECTIVE: We sought to examine whether there is any difference in the perception
      of the stimulus evoked by the NTES between patients with atopic dermatitis (AD)
      and healthy control subjects. METHODS: In all, 24 healthy control subjects and 24
      patients with AD (nonlesional skin) were stimulated on 7 body sites using the
      NTES. Qualitative differences in the evoked perceptions and quantitative
      differences in the current intensity required to evoke perception were
      statistically analyzed. RESULTS: The NTES preferentially evoked itch in patients
      with AD. The current perception threshold was statistically lower in AD than in
      healthy control subjects on 3 body sites. LIMITATIONS: Tests were performed on
      limited body areas. CONCLUSION: We demonstrated that the NTES can reveal neuronal
      sensitization to itch in nonlesional atopic skin.

PMID- 19178985
TI  - Impact of patient visiting activities on indoor climate in a medical intensive
      care unit: a 1-year longitudinal study.
AB  - BACKGROUND: Bioaerosols from numerous sources have been implicated in respiratory
      diseases. This study evaluated the characteristics and weekly variations in
      indoor air in a medical intensive care unit (ICU) in northern Taiwan for 1 year.
      It also investigated the impact of patient visiting activities on the indoor
      climate in the medical ICU. METHODS: A 4-bed room with patients in the medical
      ICU was selected for long-term air monitoring. Air temperature, relative
      humidity, CO(2), particulate matter, bacteria, and fungi were measured. RESULTS:
      Approximately 90% of the CO(2) samples exceeded 1000 ppm, and 20% of the fine
      particle samples exceeded 35 microg/m(3). The levels of bacteria and fungi varied
      during the survey period. The measured values for all indoor air characteristics
      except bacterial concentrations were higher after patient visitation than before
      patient visitation. A significant association was found between the coarse
      particle concentration and the number of patient visitors. CONCLUSION: Patient
      visiting activity impacts the indoor air quality of the ICU environment,
      especially in terms of coarse particle concentrations. Periodic monitoring of
      ventilation system efficiency is needed to ensure optimal indoor air quality.

PMID- 19178988
TI  - Influence of crop types and soil properties on radionuclide soil-to-plant
      transfer factors in tropical and subtropical environments.
AB  - This paper presents a descriptive statistical analysis of radionuclide soil-to
      plant transfer factors (Fv) for tropical and subtropical environments. These
      values were collected from previous databases and standard publications with the
      objective of contributing to the IAEA Technical Report Series: Handbook of
      parameter values for the prediction of radionuclide transfer to humans in
      terrestrial and freshwater environments. More than 2200 Fv values of different
      radionuclides were gathered and arranged into specific databases, detailing
      relevant information regarding the environments where this parameter was
      calculated. This study explores the dependence of Fv values to crop types, and
      soil properties. The wide variability and uncertainty observed in calculated Fv
      values were considerably reduced when the data was independently grouped into
      clusters containing the same radionuclide/plant group/soil type combinations. For
      each cluster the principal statistical quantities were determined. Using these
      quantities, the Fv distributions of each data set was explored. Fv probability
      distribution is discussed to clarify the use of this empirical parameter in
      radioecological and radiological assessment models.

PMID- 19178986
TI  - Acetylcholine receptor and behavioral deficits in mice lacking apolipoprotein E.
AB  - Apolipoprotein E (apoE) is involved in the risk to develop sporadic Alzheimer's
      disease (AD). Since impaired central acetylcholine (ACh) function is a hallmark
      of AD, apoE may influence ACh function by modulating muscarinic ACh receptors
      (mAChRs). To test this hypothesis, mAChR binding was measured in mice lacking
      apoE and wild type C57BL/6J mice. Mice were also tested on the pre-pulse
      inhibition, delay eyeblink classical conditioning, and 5-choice serial reaction
      time tasks (5-SRTT), which are all modulated by ACh transmission. Mice were also
      given scopolamine to challenge central mAChR function. Compared to wild type
      mice, mice lacking apoE had reduced number of cortical and hippocampal mAChRs.
      Scopolamine had a small effect on delay eyeblink classical conditioning in wild
      type mice but a large effect in mice lacking apoE. Mice lacking apoE were also
      unable to acquire performance on the 5-SRTT. These results support a role for
      apoE in ACh function and suggest that modulation of cortical and hippocampal
      mAChRs might contribute to genotype differences in scopolamine sensitivity and
      task acquisition. Impaired apoE functioning may result in cholinergic deficits
      that contribute to the cognitive impairments seen in AD.

PMID- 19178987
TI  - Age-related memory impairments due to reduced blood glucose responses to
      epinephrine.
AB  - Increases in blood glucose levels are an important component of the mechanisms by
      which epinephrine enhances memory formation. The present experiments addressed
      the hypothesis that a dysfunction in the blood glucose response to circulating
      epinephrine contributes to age-related memory impairments. Doses of epinephrine
      and glucagon that significantly increased blood glucose levels in young adult
      rats were far less effective at doing so in 2-year-old rats. In young rats,
      epinephrine and glucose were about equally effective in enhancing memory and in
      prolonging post-training release of acetylcholine in the hippocampus. However,
      glucose was more effective than epinephrine in enhancing both memory and
      acetylcholine release in aged rats. These results suggest that an uncoupling
      between circulating epinephrine and glucose levels in old rats may lead to an age
      related reduction in the provision of glucose to the brain during training. This
      in turn may contribute to age-related changes in memory and neural plasticity.

PMID- 19178989
TI  - Microbiology of odontogenic infections in deep neck spaces: a retrospective
      study.
AB  - The primary treatment of deep neck spaces odontogenic infection (DNSOI) with
      suppuration is surgery. Systemic antimicrobial therapy is an important adjunct.
      The initial prescription of antimicrobial therapy is empirical. Over the last
      decade we have observed a change in practice with the use of second-generation
      cephalosporins, in conjunction with metronidazole, replacing benzylpencillin and
      metronidazole. More recently evidence has emerged suggesting that antimicrobial
      resistance in nosocomial infections could be related to the widespread use of
      second and third-generation cephalosporins. This study was therefore initiated to
      determine whether this change in prescribing was justified. A total of 75 cases
      were retrospectively identified by scrutiny of the operating theatre data. These
      patients presented with significant DNSOI that required surgical drainage.
      Streptococcus milleri and mixed anaerobes were predominant. Only in three cases
      (4%) there were penicillin-resistant microorganisms. The substitution of
      benzylpenicillin for cefuroxime as an initial empiric therapy for DNSOI seems
      likely to have been equally efficacious in the large majority of cases. On the
      other hand, studies in preference of cephalosporins are based on in vitro trials.
      A multi-centre randomized controlled clinical trial directly comparing initial
      empiric second-generation cephalosporin therapy with benzylpenicillin in non
      allergic patients is justified.

PMID- 19178990
TI  - Bureaucratic Itineraries in Colombia. A theoretical and methodological tool to
      assess managed-care health care systems.
AB  - Steady increases in the number of Colombians insured by the health care system
      contrasts with the hundreds of thousands of legal actions interposed to warrant
      citizen's right to health. This study aims to analyze the relationships among
      patients' experiences of denials by the system, the country's legal mechanisms,
      and the functioning of insurance companies and service providing institutions. We
      conducted a mixed-methods case study in Bogota and present a quantitative
      description of 458 cases, along with semi-structured interviews and an in-depth
      illness history. We found that Colombians' denials of care most commonly include
      appointments, laboratory tests or treatments. Either insurance companies or
      service providing institutions use the system's legal structure to justify the
      different kinds of denials. To warrant their right to health care, citizens are
      forced to interpose legal mechanisms, which are largely ruled in favor, but
      delays result in a progressive and cumulative pattern of harmful consequences, as
      follows: prolongation of suffering, medical complications of health status,
      permanent harmful consequences, permanent disability, and death. We diagram the
      path that Colombians need to follow to have their health care claims attended by
      the system in a matrix called Bureaucratic Itineraries. Bureaucratic Itineraries
      is a theoretical and methodological construct that links the personal experience
      of illness with the system's structure and could be an important tool for
      understanding, evaluating and comparing different systems' performances. In this
      case, it allowed us to conclude that managed care in Colombia has created complex
      bureaucracies that delay and limit care through cost-containment mechanisms,
      which has resulted in harmful consequences for people's lives.

PMID- 19178991
TI  - Effects of maternal glycemia on fetal heart rate in pregnancies complicated by
      pregestational diabetes mellitus.
AB  - OBJECTIVE: To investigate the influence of maternal glycemia on fetal heart rate
      (FHR) parameters analyzed by computerized cardiotocography in fetuses of diabetic
      mothers in the third trimester. STUDY DESIGN: Thirty-nine pregnant women with
      pregestational diabetes mellitus were studied prospectively. The inclusion
      criteria were a diagnosis of pregestational diabetes, singleton pregnancy between
      36 and 40 weeks, and absence of fetal abnormalities. Computerized
      cardiotocography (System 8002) was performed over a period of 60 min and
      capillary glycemia was measured immediately before and 30 and 60 min after the
      beginning of the exam. The evaluations were done 2 h after lunch. RESULTS:
      Nineteen patients (48.7%) presented mean glycemia > or =120 mg/dL. The mean basal
      FHR was 136.7+/-10.0 bpm in the group with glycemia <120 mg/dL and 144.8+/-9.4
      bpm in the group with glycemia > or =120 mg/dL (p=0.013, Student's t test). There
      was a significant positive correlation (Pearson's test, p=0.0001, r=0.57) between
      basal FHR and mean glycemia. A significant negative correlation was observed
      between short-term variation and mean glycemia (Pearson's test, p=0.003, r=
      0.47). No significant differences were observed between the other indices
      evaluated by computerized cardiotocography and glycemia. CONCLUSIONS: Maternal
      hyperglycemia at the time of cardiotocography is associated with elevated FHR. It
      seems to be important to understand how FHR parameters are influenced by maternal
      glycemic status at the time of fetal assessment in pregnancies complicated by
      diabetes.

PMID- 19178992
TI  - The role of arginine 38 in horseradish peroxidase enzyme revisited: a
      computational investigation.
AB  - Molecular dynamics simulations on hydrogen peroxide complex with wild-type (WT)
      and Arg38Leu mutated (R38L) Horseradish Peroxidase (HRP) were carried out over
      nanoseconds timescale in water solution at 300 K. Comparison of the results
      provides interesting insights about the role of highly conserved Arg38 and His42
      residues in the chemical features of HRP, underlying its biological activity
      which initiates with Compound0 (Cpd0). In the WT-HRP enzyme current molecular
      dynamics simulations show, for the first time, that Arg38 residue: i) prevents
      the entrance of water inside the reaction cavity, hence providing a hydrophobic
      reactive scenario, ii) it maintains the distance between His42 and heme-H(2)O(2)
      complex suitable for the occurrence of proton transfer reaction leading,
      thereafter, to heme-H(2)O(2) disruption according to Poulos-Kraut mechanism. On
      the other hand, R38L mutant can be considered as a "wet enzyme" where the
      presence of water solvent molecules in the heme reaction pocket, unfavoring the
      initial heme-H(2)O(2) complex formation, decreases the catalytic efficiency in
      agreement with experimental kinetics measurements. Furthermore, we note that
      Arg38Leu mutation pushes the His42 residue far from the heme-H(2)O(2) complex,
      making unlikely a direct proton transfer and suggesting that, in the mutant, a
      solvent water molecule could be involved in the first step of the Poulos-Kraut
      mechanism.

PMID- 19178993
TI  - Perioperative intravesical therapy: effective treatment, unfulfilled promises.

PMID- 19178994
TI  - Overactive bladder is a dynamic syndrome.

PMID- 19178995
TI  - Inhibition of the insulin-like growth factor 1 receptor pathway enhances the
      antitumor effect of cisplatin in human malignant mesothelioma cell lines.
AB  - Human malignant mesothelioma (HMM) is a fatal tumor and is poorly responsive to
      current therapeutic regimens. The insulin-like growth factor 1 receptor (IGF-1R)
      pathway is activated in HMM cell lines and tissues. Treatment with AG1024, an
      inhibitor of the IGF-1R pathway, significantly decreased cell proliferation and
      attenuated the phosphorylation of Akt and p44/42. In addition, it significantly
      enhanced the cytotoxic effects of cisplatin in HMM cell lines. This study
      supports the conjecture that inhibition of the IGF-1R pathway may be a useful
      target for reducing toxicity and alleviating chemoresistance to traditional
      anticancer drugs in HMM patients.

PMID- 19178996
TI  - Removal efficiency of gaseous benzene using lanthanide-doped mesoporous titania.
AB  - The adsorptive removal of benzene from cerium- and lanthanum-doped mesoporous
      TiO2 adsorbents was performed in a continuous-flow, fixed-bed reactor. The
      influences of lanthanide content and adsorption temperature were investigated.
      The adsorption efficiency of benzene was remarkably promoted in the presence of
      lanthanide. The adsorption capacity for benzene increased with lanthanide dosage,
      which was attributed to the enhancement in a specific surface area. It was
      determined that 5 mol% rare earth metal was the optimal amount for the highest
      benzene-adsorption, irrespective of adsorption temperature. Furthermore, the
      drastic reduction of adsorption capacities at higher temperature implied that
      benzene molecules were weakly adsorbed to the adsorbents. Additionally, X-ray
      photoelectron spectroscopy showed a correlation between the adsorption behavior
      and the chemical properties of mesostructure materials, typically the interaction
      of surface hydroxyl groups and the pi-electron of benzene, and the formation of
      sigma-bonding and d-pi* back-donation between the adsorbent and gaseous
      adsorbate.

PMID- 19178997
TI  - Entrapment of iron nanoparticles in calcium alginate beads for groundwater
      remediation applications.
AB  - Zero-valent iron nanoparticles (nZVI) have been successfully entrapped in
      biopolymer, calcium (Ca)-alginate beads. The study has demonstrated the potential
      use of this technique in environmental remediation using nitrate as a model
      contaminant. Ca-alginate beads show promise as an entrapment medium for nZVI for
      possible use in groundwater remediation. Based on scanning electron microscopy
      images it can be inferred that the alginate gel cluster acts as a bridge that
      binds the nZVI particles together. Kinetic experiments with 100, 60, and 20mg
      NO(3)(-)-NL(-1) indicate that 50-73% nitrate-N removal was achieved with
      entrapped nZVI as compared to 55-73% with bare nZVI over a 2-h period. The
      controls ran simultaneously show little NO(3)(-)-N removal. Statistical analysis
      indicates that there was no significant difference between the reaction rates of
      bare and entrapped nZVI. The authors have shown for the first time that nZVI can
      be effectively entrapped in Ca-alginate beads and no significant decrease in the
      reactivity of nZVI toward the model contaminant (nitrate here) was observed after
      the entrapment.

PMID- 19178998
TI  - Preparation and characterization of activated carbon from cotton stalk by
      microwave assisted chemical activation--application in methylene blue adsorption
      from aqueous solution.
AB  - The activated carbon prepared from cotton stalk with ZnCl(2) as activation was
      investigated under microwave radiation. Effects on the yield and adsorption
      capacities of activated carbon were evaluated then, such as, microwave power,
      microwave radiation time and the impregnation ratio of ZnCl(2). It indicated that
      the optimum conditions were as follows: microwave power of 560 W, microwave
      radiation time of 9 min and the impregnation ratio of ZnCl(2) was 1.6g/g. Iodine
      number, amount of methylene blue adsorption and the yield of activated carbon
      prepared under optimum conditions were 972.92 mg/g, 193.50mg/g and 37.92%,
      respectively. Laboratory prepared activated carbons were characterized by
      pH(ZPC), SEM, FT-IR, S(BET) and pore structural parameters. Then they were used
      as adsorbent for the removal of methylene blue from aqueous solutions under
      varying conditions of initial concentration, carbon dosage and pH. It indicated
      that Langmuir isotherm was fitter than Freundlich isotherm and Temkin isotherm.

PMID- 19178999
TI  - Adsorption and desorption behavior of copper ions on Na-montmorillonite: effect
      of rhamnolipids and pH.
AB  - In this work, the effects of an anionic biosurfactant, rhamnolipid (RL), and pH
      on the adsorption and desorption of Cu(2+) ions on Na-montmorillonite were
      investigated. Adsorption studies were conducted through the addition of Cu(2+) to
      the dispersions containing pristine- and/or RL-modified clay. In the case of
      pristine clay, RL was also added simultaneously with the Cu(2+). The effect of pH
      was studied in the range between 1.0 and 8.0. The highest adsorption capacity was
      obtained at the pH of 4.7-4.8. Among the models including the Langmuir,
      Freundlich and Dubinin-Kaganer-Radushkevich isotherms; Langmuir isotherm gave a
      better fit to the experimental data. The most suitable fit for the adsorption
      kinetics of Cu(2+) was obtained with a pseudo-second-order model. It was
      determined that the adsorption capacity of the pristine clay is comparable with
      that of the activated carbon and the modification of clay with RL causes an
      increase in the adsorption rate due to the distribution of clay platelets in the
      solution.

PMID- 19179000
TI  - Distribution and speciation of heavy metals in sediments from the mainstream,
      tributaries, and lakes of the Yangtze River catchment of Wuhan, China.
AB  - A comparative study of the heavy metal (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn)
      concentrations in sediments collected from the mainstream, tributaries, and lakes
      of the Yangtze River catchment of Wuhan, China, was conducted. Compared with the
      maximum background values in Wuhan Province soils, Cd was the metal with the
      highest contamination level, especially in the mainstream, followed by Zn and Cu.
      In a few samples from tributaries and lakes, the Hg concentration was very high
      compared to background levels. The concentrations of As and Ni in all sites
      fluctuated close to background levels. Partitioning of speciation of each heavy
      metal in sediments was similar for samples taken from the mainstream,
      tributaries, and lakes. Compared to the other metals studied, Cd, Cu, Zn, and Pb
      had higher bioavailability in the three zones, which means they pose a higher
      ecological risk. Significant correlations among group a (Zn, Cu, and Pb, r>0.9)
      and group b (Cr and Ni, r=0.978) in the mainstream; Hg, Cu, Cd, and Pb in lakes
      (r>0.9); and Cu and Pb (r>0.9) in tributaries were observed using Cluster and
      correlation analysis. However, a low correlation between As and the other
      elements in the three zones was shown. Overall, 63.6% of samples from the
      mainstream, 75.0% from tributaries, and 88.9% from lakes exhibited low and
      moderate ecological risk of heavy metals, and the potential ecological risks in
      the mainstream and tributaries were higher than those in lakes.

PMID- 19179001
TI  - Removal of radioactive caesium from low level radioactive waste (LLW) streams
      using cobalt ferrocyanide impregnated organic anion exchanger.
AB  - The volumes of low level waste (LLW) generated during the operation of nuclear
      reactor are very high and require a concentration step before suitable matrix
      fixation. The volume reduction (concentration) is achieved either by co
      precipitating technique or by the use of highly selective sorbents and ion
      exchange materials. The present study details the preparation of cobalt
      ferrocyanide impregnated into anion exchange resin and its evaluation with
      respect to removal of Cs in LLW streams both in column mode and batch mode
      operations. The Kd values of the prepared exchanger materials were found to be
      very good in actual reactor LLW solutions also. It was observed that the
      exchanger performed very well in the pH range of 3-9. A batch size of 6 g l(-1)
      of the exchanger was enough to give satisfactory decontamination for Cs in actual
      reactor LLW streams. The lab scale and pilot plant scale performance of the
      exchanger material in both batch mode and column mode operations was very good.

PMID- 19179002
TI  - Adsorption and desorption characteristics of monosulfuron in Chinese soils.
AB  - Through batch equilibration experiments, the adsorption-desorption
      characteristics of monosulfuron, a new sulfonylurea herbicide widely used, were
      investigated in eight agricultural soil samples collected from China. The
      isotherms for monosulfuron adsorption were nonlinear (n ranged from 0.748 to
      0.943) and well described by the revised Freundlich equation. Data obtained from
      adsorption experiments showed that monosulfuron had weak to moderate adsorption
      capability in different soils and might readily result in leaching problems,
      which was correlated significantly with soil properties. The content and chemical
      characteristic of the soil organic matter (SOM) was considered to be one of the
      important factors leading to differences in sorption capacity. Meanwhile, the
      extent of monosulfuron adsorption on soil was at rather high level under low pH
      value conditions and decreased with increasing pH value. Besides, desorption
      hysteresis of monosulfuron were observed in most of tested soils, and was
      demonstrated to be improved with increased concentration in initial solution and
      depended significantly on SOM.

PMID- 19179003
TI  - Biodegradation of thiodiglycol, a hydrolyzate of the chemical weapon Yperite, by
      benzothiophene-desulfurizing bacteria.
AB  - Microbial degradation of thiodiglycol (bis(2-hydroxyethyl)sulfide, TDG) with
      petroleum-desulfurizing soil bacteria was examined. Among the bacteria tested,
      several strains belonging to the genera Rhodococcus and Gordonia grew on TDG as
      the sole sulfur source. The selected strain Rhodococcus sp. strain T09, which was
      re-identified as R. jostii, showed TDG degradation activity only when grown in
      the presence of TDG as the sole sulfur source. Repeat batch degradation of TDG by
      using strain T09 could be continued for over 50h, with a slight loss of activity.

PMID- 19179004
TI  - Dechlorination of 1,2,3- and 1,2,4-trichlorobenzene by the white-rot fungus
      Trametes versicolor.
AB  - The degradation of 1,2,3-, 1,3,5- and 1,2,4-trichlorobenzene (TCB) by the white
      rot fungus Trametes versicolor was studied. Time course experiments showed a
      degradation rate of 2.27 and 2.49 nmol d(-1)mg(-1) dry weight of biomass during
      the first 4d of incubation in cultures spiked with 6 mg L(-1) of 1,2,3- and 1,2,4
      TCB, respectively. A high percent of degradation of 91.1% (1,2,3-TCB) and 79.6
      (1,2,4-TCB) was obtained after 7d. However, T. versicolor was not able to degrade
      1,3,5-TCB under the conditions tested. For a range of concentrations of 1,2,4-TCB
      between 6.5 and 23 mg L(-1), a complete dechlorination of the molecule was
      observed. Cytochrome P450 monooxygenase appears to be involve in the first step
      of 1,2,4-TCB degradation, as evidenced by marked inhibition of both
      dechlorination and degradation of 1,2,4-TCB in the presence of the known cyt P450
      inhibitors 1-aminobenzotriazole and piperonyl butoxide. Four intermediates formed
      from 1,2,4-TCB degradation were detected the second day of incubation, which did
      not appear the seventh day: 2,3,5-trichloromuconate, its corresponding
      carboxymethylenebutenolide, 2- or 5-chloro-4-oxo-2-hexendioic acid and 2- or 5
      chloro-5-hydroxy-4-oxo-2-pentenoic acid. Based on these results, a degradation
      pathway of 1,2,4-TCB through cyt P450 monooxygenase and epoxide hydrolase was
      proposed.

PMID- 19179005
TI  - Growth responses and cadmium accumulation of Mirabilis jalapa L. under
      interaction between cadmium and phosphorus.
AB  - Based on the identification of Mirabilis jalapa L. as a new Cd-hyperaccumulating
      ornamental, the growth response of the plant to interaction between cadmium (Cd)
      and phosphorus (P), its effect on the Cd accumulation in the species and relevant
      mechanisms were further investigated by the pot-culture experiment with chemical
      analyses and the X-ray absorption near edge structure spectra (XANES). It showed
      that the leaf, shoot and root biomass (as dry matter) increased with an increase
      in P supplies from 20 to 100 mg kg(-1) at various tested Cd levels except 10 mg
      kg(-1). The Cd accumulation in the leaves and shoots significantly decreased with
      increasing P concentrations from 20 to 500 mg kg(-1) at the Cd concentrations
      from 10 to 50 mg kg(-1), except the Cd level at 100 mg kg(-1). It was also found
      that the translocation factor of Cd in M. jalapa L. reached the maximum at
      different tested Cd levels when the concentration of added P was 100 mg kg(-1),
      but the bioaccumulation factor of Cd decreased with increasing P. This changing
      law may be responsible for the mechanism of P immobilizing Cd. The investigation
      using the P-K edge XANES showed the spectra of adsorbed phosphate in the shoots
      exhibited a stronger white-line peak than that in the leaves and roots, and the
      oscillation near 2165eV was more intense. Besides, the P-K edge XANES spectra for
      M. jalapa L. indicated P may exist as Cd-phosphate. Thus, it can be inferred that
      the addition of P at appropriate contents may be a useful approach to enhance the
      plant growth and to immobilize Cd in the Cd-contaminated soil. Furthermore, P and
      Cd may form a deposit in plants to tolerate Cd toxicity for reducing the degree
      of the structural damage of the plant.

PMID- 19179006
TI  - Enhanced reductive dechlorination of PCE DNAPL with TBOS as a slow-release
      electron donor.
AB  - Tetrabutoxysilane (TBOS), which yields 1-butanol upon abiotic hydrolysis, was
      evaluated as a slow-release substrate for the reductive dechlorination of
      tetrachloroethylene (PCE) as a dense non-aqueous-phase liquid (DNAPL).
      Dechlorination was achieved using an anaerobic binary mixed (BM) culture, which
      consisted of the Pt. Mugu (PM) and the Evanite (EV) mixed cultures. In batch
      reactor experiments, TBOS was mixed with PCE DNAPL to achieve different PCE mol
      fractions (PCEmol/(PCE mol+TBOSmol)), and different PCE aqueous concentrations
      based on Raoult's Law. The reductive dechlorination activity was determined based
      on the amount of chloride ions released and the mass balances of the
      transformation products formed. The mass balances of the total chlorinated
      aliphatic hydrocarbons (CAHs) between water, NAPL and gas phases were performed
      using independently measured NAPL/water partition coefficients. The amounts of
      chloride released (directly measured in aqueous samples) agreed with the total
      chloride produced based on the mass balances. The abiotic rates of TBOS
      hydrolysis were first-order with respect to TBOS NAPL concentration. A higher
      electron transfer efficiency to dechlorination was correlated with lower rates of
      TBOS hydrolysis. The total amounts of PCE DNAPL and TBOS were important factors
      for the reductive dechlorination of PCE. The dechlorination activity was
      suppressed at high NAPL concentrations. Direct contact of the PCE/TBOS NAPL
      mixture may have caused toxicity to the dechlorinating bacteria. Decreases in pH
      likely lowered the microbial activity for reductive dechlorination due to the
      accumulation of acetate and/or butyrate. These studies showed the potential of
      TBOS as a slow-release substrate for enhancing bioremediation of DNAPL
      contaminated sites.

PMID- 19179007
TI  - Modeling and multi-response optimization of pervaporation of organic aqueous
      solutions using desirability function approach.
AB  - The factorial design of experiments and desirability function approach has been
      applied for multi-response optimization in pervaporation separation process. Two
      organic aqueous solutions were considered as model mixtures, water/acetonitrile
      and water/ethanol mixtures. Two responses have been employed in multi-response
      optimization of pervaporation, total permeate flux and organic selectivity. The
      effects of three experimental factors (feed temperature, initial concentration of
      organic compound in feed solution, and downstream pressure) on the pervaporation
      responses have been investigated. The experiments were performed according to a
      2(3) full factorial experimental design. The factorial models have been obtained
      from experimental design and validated statistically by analysis of variance
      (ANOVA). The spatial representations of the response functions were drawn
      together with the corresponding contour line plots. Factorial models have been
      used to develop the overall desirability function. In addition, the overlap
      contour plots were presented to identify the desirability zone and to determine
      the optimum point. The optimal operating conditions were found to be, in the case
      of water/acetonitrile mixture, a feed temperature of 55 degrees C, an initial
      concentration of 6.58% and a downstream pressure of 13.99 kPa, while for
      water/ethanol mixture a feed temperature of 55 degrees C, an initial
      concentration of 4.53% and a downstream pressure of 9.57 kPa. Under such optimum
      conditions it was observed experimentally an improvement of both the total
      permeate flux and selectivity.

PMID- 19179008
TI  - 4-Chlorophenol degradation by pulsed high voltage discharge coupling internal
      electrolysis.
AB  - A system of pulsed high voltage discharge coupling internal electrolysis
      (PHVDCIE) in water has been developed to remove 4-chlorophenol (4-CP). The
      hydrogen peroxide formed by discharge was little utilized by 4-CP degradation in
      the sole discharge system, but most of the hydrogen peroxide could be utilized in
      the PHVDCIE system to form hydroxyl radicals for the production of Fe(2+). The
      Fe(2+) was generated in the cell reaction and was reacted with the hydrogen
      peroxide through the Fenton's reaction. The formation rate of hydroxyl radical
      was increased in the PHVDCIE system. It was 5.28 x 10(-7)mol L(-1)s(-1) with
      bubbling oxygen but it was 1.49 x 10(-7)mol L(-1)s(-1) in the sole discharge
      system. With increase in the yields of hydroxyl radical, the 4-CP removal was
      sped up. The removal efficiency of 4-CP was improved to more than 90%
      correspondingly by 36 min discharge in the PHVDCIE system. With the promotion of
      4-CP degradation, more intermediate products such as formic, acetic and oxalic
      acid were produced.

PMID- 19179009
TI  - Novel heavy-metal adsorption material: ion-recognition P(NIPAM-co-BCAm) hydrogels
      for removal of lead(II) ions.
AB  - A novel polymeric lead(II) adsorbent is prepared by incorporating benzo-18-crown
      6-acrylamide (BCAm) as metal ion receptor into the thermo-responsive poly(N
      isopropylacrylamide) (PNIPAM) hydrogel. Both stimuli-sensitive properties and the
      Pb(2+)-adsorption capabilities of the prepared P(NIPAM-co-BCAm) hydrogels are
      investigated. The prepared P(NIPAM-co-BCAm) hydrogels exhibit good ion
      recognition and Pb(2+)-adsorption characteristics. When crown ether units capture
      Pb(2+) and form BCAm/Pb(2+) host-guest complexes, the lower critical solution
      temperature (LCST) of the hydrogel shifts to a higher temperature due to both the
      repulsion among charged BCAm/Pb(2+) groups and the osmotic pressure within the
      hydrogel. The adsorption results at different temperatures show that P(NIPAM-co
      BCAm) hydrogels adsorb Pb(2+) ions at temperature lower than the LCST, but
      undergo desorption at temperature higher than the LCST due to the "stretch-to
      shrink" configuration change of copolymer networks which is triggered by the
      change in environmental temperature. This kind of ion-recognition hydrogel is
      promising as a novel adsorption material for adsorption and separation of Pb(2+)
      ions. The adsorption and desorption of Pb(2+) could be rationally achieved by
      simply changing the environmental temperature.

PMID- 19179010
TI  - Aqueous p-chloronitrobenzene decomposition induced by contact glow discharge
      electrolysis.
AB  - Aqueous p-chloronitrobenzene (PCNB) decomposition induced by contact glow
      discharge electrolysis under various reaction conditions was investigated.
      Experimental results showed that, at voltage 450-550 V and initial concentration
      50-500 mg/L, the decay of PCNB can be described by a first-order reaction
      kinetics of In(C(0)/C(t))=0.029 (I/V)t, where C(0), I, V and C(t) denote the
      initial PCNB concentration (mg/L), applied current (A), solution volume (L) and
      instantaneous PCNB concentration (mg/L) at treatment time t (min). Major
      intermediate products such as 4-nitrophenol, 2-chloro-5-nitrophenol, oxalic and
      formic acids, chloride and nitrate ions were identified by LC/MS and IC,
      respectively. No chlorophenols present indicated that the dechlorination was
      easier than denitration from the aromatic ring of PCNB. Formation of hydrogen
      peroxide during the degradation was observed and the role of Fenton's reaction
      was examined. Hydroxyl radicals may be the most responsible species for PCNB
      degradation.

PMID- 19179011
TI  - Laser-assisted atom probe analysis of sol-gel silica layers.
AB  - Semi-conducting nanocrystals embedded in a non-conducting matrix of silicate
      glass may be used as non-volatile data storage device. Structures of silicate
      glasses are conveniently produced by a sol-gel process, which offers the
      possibility to coat tip-shaped substrates with a silica layer. The study presents
      first results of their local chemical analysis by laser-assisted atom probe. Till
      date the exact mechanisms of laser pulsing are still controversial. But it is
      common sense that there is an at least considerable heating effect on the tip,
      which leads to a short temperature rise and a prolonged cooling period in
      materials of low heat conductivity. This effect alters the shape of mass peaks
      and is examined here using a one-dimensional model of heat transport.

PMID- 19179012
TI  - Thermal stability of a Co/Cu giant magnetoresistance (GMR) multilayer system.
AB  - Critical limitations exist regarding the thermal stability of multilayer giant
      magnetoresistance (GMR) sensors due to significant contribution of layer
      interfaces and grain boundaries to their performance. This paper addresses the
      stability of, and thermal reaction in Co/Cu magnetoresistive systems. Thin film
      multilayers were deposited by ion beam sputtering on top of preformed tungsten
      tips. The multilayers were then analyzed by a wide-angle tomographic atom probe
      (WATAP) in the as-prepared state and after heat treatments in the temperature
      range from 150 to 550 degrees C. As revealed by the WATAP analysis, Co
      breakthroughs along grain boundaries in the Cu spacers appear at 450 degrees C.
      This morphological change leads to a deterioration of the GMR effect due to the
      magnetostatic ferromagnetic coupling between Co layers. Furthermore, a strong
      effect of Cu layers faceting is observed after annealing in the same temperature
      range, which may lead to the deterioration of the layered structure on high-angle
      grain boundaries.

PMID- 19179013
TI  - Grievous penile electrical burns.

PMID- 19179014
TI  - Television-supported self-help for problem drinkers: a randomized pragmatic
      trial.
AB  - OBJECTIVES: To test the effectiveness of a television-supported self-help
      intervention for problem drinking. METHODS: Dutch television viewers (N=181)
      drinking in excess of the guidelines for low-risk alcohol use were randomly
      assigned either to the Drinking Less TV self-help course (consisting of five
      televised sessions supplemented by a self-help manual and a self-help website) or
      to a waitlisted control group. To ensure trial integrity, intervention delivery
      was mimicked beforehand by sending intervention participants weekly DVDs in
      advance of the actual telecasts in 2006. Pre-post assessments were carried out on
      both groups, as well as a 3-month follow-up assessment on the intervention group
      to study effect maintenance. The primary outcome measure was low-risk drinking.
      RESULTS: The intervention group was more successful than the waitlist group in
      achieving low-risk drinking at post-intervention (OR=9.4); the effects were
      maintained in the intervention group at 3-month follow-up. CONCLUSIONS: The low
      threshold television-based course Drinking Less appears effective in reducing
      problem drinking.

PMID- 19179015
TI  - Risk factors for young adult substance use among women who were teenage mothers.
AB  - Teenage mothers may not "mature out" of substance use during young adulthood, and
      this non-normative trajectory of use may contribute to negative outcomes for
      teenage mothers and their offspring. Pregnant teenagers (age range=12-18 years;
      68% Black) were recruited from a prenatal clinic and interviewed about their
      substance use, and subsequently re-interviewed six and ten years later (n=292).
      Consistent with the literature, early tobacco and marijuana use were risk factors
      for young adult use. Other substance use, peer adolescent use and mental health
      indicators were more important than race and socioeconomic status (SES) in
      determining which teenage mothers would use tobacco, engage in binge drinking,
      and use marijuana as young adults. However, race and SES were significant
      predictors of quitting tobacco use and marijuana use by the 10-year follow-up.
      Depression was associated with both persistent tobacco use and marijuana use in
      teenage mothers. These results illustrate the long-term consequences of teenage
      childbearing and identify modifiable risk factors for later health risks that
      should be addressed among younger mothers.

PMID- 19179016
TI  - High-grade urothelial carcinoma of the urinary bladder showing acquisition of
      microcystic histology in the penile metastasis: histogenetic considerations.
AB  - Microcystic urothelial carcinoma is a rare variant of transitional cell carcinoma
      with an indefinite prognostic significance. Herein, we report for the first time
      the acquisition of microcystic histology in the penile metastasis of a high-grade
      urothelial carcinoma of the urinary bladder. The patient died of disseminated
      disease six months later. The immunohistochemical evaluation of mucin expression
      in the primitive and metastatic tumor suggests that the microcystic histotype may
      descend from the primitive urothelial carcinoma through a process of
      dedifferentiation and subsequent redifferentiation. In conclusion, the
      acquisition of microcystic histology seems to be associated with an aggressive
      clinical course of the urothelial carcinoma, as already suggested by other
      authors. Future studies investigating mucin expression in microcystic urothelial
      carcinoma may help to define the histogenesis of this tumor.

PMID- 19179017
TI  - [Oocyte and embryo quality and outcome of ICSI cycles in patients with polycystic
      ovary syndrome (PCOS) versus normo-ovulatory].
AB  - OBJECTIVE: To compare the oocyte and embryo quality and outcomes in polycystic
      ovary syndrome (PCOS) patients and normo-ovulatory women undergoing
      intracytoplasmic sperm injection (ICSI) cycles. MATERIALS AND METHODS: We studied
      retrospectively 100 controlled ovarian stimulation cycles for ICSI in women with
      PCOS and 200 cycles in normo-ovulatory women. Every PCOS woman was paired
      according to age with two normo-ovulatory woman undergoing ICSI during the same
      study period. A long protocol of gonadotrophin releasing hormone (GNRH) agonist
      was carried out in all patients. The main outcome measures evaluated were:
      cancellation of the cycles, number of aspirated follicles, oocyte maturity,
      fertilization rate, embryo quality pregnancy and implantation rates, clinical
      abortion rate, multiple pregnancy rate and the "take-home baby" rate. Khi(2) test
      and Student t test were used for differences between normo-ovulatory and PCOS
      patients and the limit of significance was set at p<0,05. RESULTS: ICSI was
      performed for male infertility in most cases (79% in PCOS group vs 79,5%; NS).
      There was no significant difference in term of cancellation rate (5,5% in PCOS
      group vs 5%; NS). The mean number of follicles was higher in patients with PCOS
      (18,1+/-8,5 vs 9,4+/-5,5; p<0,001). Oocyte mature rate (67% vs 52%; p<0,001),
      fertilization rate (75% vs 63,7%; p<0,001) and grade 1 embryo rate (69% vs 53%;
      p<0,001) were significantly higher in PCOS group. The mean number of transferred
      embryos was similar in the two groups (2,46+/-0,5 vs 2,54+/-1,01; NS).
      Implantation rate (16,6% vs 12,1%; NS), clinical pregnancy rate per transfer
      (31,5% vs 24%; NS) and Live birth rate (22% vs 20%; NS) did not differ
      statistically in the two groups. Twin and triplet pregnancies rates were similar
      in the two groups (20% vs 16,7%; NS and 6,6% vs 7,1% ; NS respectively).
      Miscarriage rate was higher in PCOS group but this did not reach the statistical
      significance (26,6% vs 16,6%; NS). CONCLUSION: PCOS patients showed better global
      oocyte and embryo quality. However, pregnancy and live birth rates were similar
      in the two groups when number and quality of transferred embryos are equivalent.

PMID- 19179018
TI  - [Unusual complication of uterine leiomyoma: spontaneous avulsion with massive
      hemoperitoneum].
AB  - A 25-year-old woman gravida 0 was seen for haemoperitoneum secondary to
      spontaneous avulsion of a uterine leiomyoma. It is a life-threatening
      complication. A myomectomy was performed. Through a case, we report a revue of
      the literature of haemoperitoneum complicating uterine leiomyoma.

PMID- 19179019
TI  - [When an enterovirus emerges].
AB  - Most of enterovirus infections are benign and the rate of mortality is low in
      countries with temperate climates. But since the late 1990s, Enterovirus 71 (EV
      71) has become much more aggressive in Asian countries, with the outcome of a
      neurogenic pulmonary oedema syndrome and it is responsible for huge epidemics.
      The virological diagnosis rely upon viral isolation and identification by sero
      neutralization, and upon the detection of specific IgM by ELISA and viral RNA by
      RT-PCR. There is no specific treatment to fight this virus, but innovative
      strategies, especially based on interfering RNA, are under investigation.

PMID- 19179020
TI  - Educational attainment and smoking among women: risk factors and consequences for
      offspring.
AB  - We examine the association between education and smoking by women in the
      population, including smoking during pregnancy, and identify risk factors for
      smoking and the consequences of smoking in pregnancy for children's smoking and
      behavioral problems. Secondary analyses of four national data sets were
      implemented: The National Survey of Drug Use and Health (2006), the National
      Longitudinal Survey of Youth (1979-2004); the National Longitudinal Survey of
      Adolescent Health (Wave III); National Health and Nutrition Examination Survey
      (2005-2006). The lower the level of education, the greater the risk of being a
      current smoker, smoking daily, smoking heavily, being nicotine dependent,
      starting to smoke at an early age, having higher levels of circulating cotinine
      per cigarettes smoked, and continuing to smoke in pregnancy. The educational
      gradient is especially strong in pregnancy. Educational level and smoking in
      pregnancy independently increase the risk of offspring smoking and antisocial and
      anxious/depressed behavior problems. These effects persist with control for other
      covariates, except maternal age at child's birth, which accounts for the impact
      of education on offspring smoking and anxious/depressed behavior problems. Women
      with low education should be the target of public health efforts toward reducing
      tobacco use. These efforts need to focus as much on social conditions that affect
      women's lives as on individual level interventions. These interventions would
      have beneficial effects not only for the women themselves but also for their
      offspring.

PMID- 19179021
TI  - A reverse vaccinology approach to swine dysentery vaccine development.
AB  - Swine dysentery (SD) is a mucohaemorrhagic colitis of pigs resulting from
      infection of the large intestine with the anaerobic intestinal spirochaete
      Brachyspira hyodysenteriae. Whole-cell bacterin vaccines are available to help
      control SD, but their performance has been inconsistent. This study aimed to use
      a reverse vaccinology approach to identify B. hyodysenteriae proteins for use as
      recombinant vaccine components. Nineteen open reading frames (ORFs) predicted to
      encode potential vaccine candidate molecules were identified from in silico
      analysis of partial genomic sequence data. The distribution of these ORFs among
      strains of B. hyodysenteriae was investigated by PCR, and widely distributed ORFs
      were cloned. The products were screened with a panel of immune pig sera, and from
      these a subset of conserved, immunogenic proteins was selected. Mice immunized
      intramuscularly with these recombinant proteins developed specific systemic
      antibody responses to them, and their sera agglutinated B. hyodysenteriae cells
      in vitro. In a pilot experiment, eight pigs were vaccinated twice intramuscularly
      with a combination of four of the proteins. The pigs developed antibodies to the
      proteins, and following experimental challenge only one developed SD compared to
      five of nine non-vaccinated control pigs. Although these differences in incidence
      were not significant, they indicated a trend towards protection using the
      recombinant proteins as immunogens. This study demonstrates that the reverse
      vaccinology approach has considerable potential for use in developing novel
      recombinant vaccines for SD.

PMID- 19179022
TI  - Isolation and characterization of the equine influenza virus causing the 2006
      outbreak in Chile.
AB  - The equine influenza virus is the causal agent of influenza in horses. In July
      2006, horses from various regions of Chile presented fever, serious nasal
      discharge, dry cough, anorexia and depression. Here we describe the isolation and
      characterization of the virus responsible for this outbreak. The virus was
      identified as equine influenza virus H3N8, since haemagglutination was inhibited
      by an anti-A/equi/1/H3N8 serum, but not by an anti-A/equi/1/H7N7 serum. The
      isolate was named A/equi/2/Lonquen/06 (H3N8). In addition, we describe the
      isolation and sequencing of the haemagglutinin, neuraminidase and nucleoprotein
      genes of this new isolate. Sequence alignments show important differences with
      the Santiago/85 isolate and a closer relation to North American isolates,
      especially with the Florida lineage, and to Argentina isolates from 1990s.

PMID- 19179023
TI  - Onset and duration of protective immunity against clinical disease and renal
      carriage in dogs provided by a bi-valent inactivated leptospirosis vaccine.
AB  - Protection against clinical disease and prevention of the renal carrier state
      remain the key objectives of vaccination against leptospirosis in the dog. In the
      present paper, groups of dogs were vaccinated twice with a commercial bacterin
      (EURICAN L) containing Leptospira interrogans serovars icterohaemorrhagiae and
      canicola and challenged with heterologous representatives of both serovars at 2
      weeks (onset of immunity) or 14 months (duration of immunity) after the second
      vaccination. Control dogs were not vaccinated against leptospirosis and kept with
      the vaccinated dogs. The challenges, irrespective of the serovar, reliably
      produced clinical signs consistent with Leptospira infection in the control pups
      with up to 60% mortality. As expected clinical disease in the adult controls was
      less severe, but we were able to induce morbidity and mortality as well. Under
      these extreme challenge conditions, clinical signs in the vaccinated dogs were
      rare, and when observed, mild and transient in nature. Following experimental
      infection, 100% of the control pups and 83% of the adult controls became renal
      carriers. Despite the heavy challenges, none of the 18 vaccinated puppies (onset
      of immunity studies) and only 2 out of the 16 vaccinated adult dogs (duration of
      immunity studies) developed a renal carrier state. These results show that a
      primary course of two doses of EURICAN L provided quick onset and long-term
      protection against both clinical leptospirosis and the renal carrier stage. This
      vaccine should provide veterinarians with a powerful tool to prevent clinical
      disease in dogs and zoonotic transmission of leptospirosis to humans.

PMID- 19179024
TI  - Progestins in the menopause in healthy women and breast cancer patients.
AB  - At present, more than 200 progestin compounds are synthetized, but their
      biological effects are different: this is function of their structure, receptor
      affinity, metabolic transformations, the target tissues considered, dose. The
      action of progestins in breast cancer is controversial; some studies indicate an
      increase in breast cancer incidence, others show no differences, and yet others
      indicate a decrease. Many studies agree that treatment with progestins plus
      estrogens at a low dose and during a limited period (less than 5 years) can have
      beneficial effects in peri- and post-menopausal women. It was demonstrated that
      various progestins (e.g. nomegestrol acetate, medrogestone, promegestone), as
      well as tibolone and its metabolites, can block the enzymes involved in estradiol
      bioformation (sulfatase, 17beta-hydroxysteroid dehydrogenase) in breast cancer.
      Progesterone is converted into various metabolic products: in normal breast
      tissue the transformation is mainly to 4-ene derivatives, whereas in the tumor
      tissue 5alpha-pregane derivatives are predominant. Aromatase activity is the last
      step in the formation of estrogens by the conversion of androgens. In recent
      studies it was shown that 20alpha-dihydroprogesterone, a metabolite found mainly
      in normal breast tissue and having anti-proliferative properties, can act as an
      anti-aromatase agent. The data suggest the possible utilization of this compound
      in breast cancer prevention. In conclusion, in order to clarify and better
      understand the response of progestins in breast cancer (incidence and mortality),
      as well as in hormone replacement therapy or in endocrine dysfunction, new
      clinical trials are necessary using other progestins in function of the dose and
      period of treatment.

PMID- 19179025
TI  - Changes in circulating cytokine levels in midlife women with psychological
      symptoms with selective serotonin reuptake inhibitor and Japanese traditional
      medicine.
AB  - OBJECTIVE: The aim of the present study was to compare the effects on serum
      cytokine concentrations of paroxetine, a selective serotonin re-uptake inhibitor,
      and kamishoyosan, a Japanese traditional medicine, in midlife women with
      psychological symptoms. METHODS: Seventy-six women with psychological symptoms
      such as anxiety and mild depression as menopausal symptoms were enrolled in this
      study. Thirty-eight women received oral administration of 10mg paroxetine every
      day, and 38 women received oral administration of kamshoyosan every day for 6
      months. Overall climacteric symptoms were assessed using Greene's climacteric
      scale. Serum levels of cytokines were measured using a multiplexed human cytokine
      assay. RESULTS: Greene's total scores in both women treated with paroxetine and
      in women treated with kamishoyosan decreased significantly. Percentage decreases
      in Greene's total, psychological and vasomotor scores during the 6-month period
      in the paroxetine group were significantly greater than those in the kamishoyosan
      group. Serum IL-6 concentration in women treated with paroxetine decreased
      significantly. Serum concentrations of IL-8, IL-10, macrophage inflammatory
      protein (MIP)-1beta and monocyte chemoattractant protein-1 in women treated with
      paroxetine decreased significantly. On the other hand, serum IL-6 concentration
      in women treated with kamishoyosan decreased significantly, but other serum
      concentrations did not change significantly. CONCLUSION: Decrease in IL-6
      concentration may be involved in the mechanism of the actions of both paroxetine
      and kamishoyosan in women with psychological symptoms, and IL-6 may therefore be
      useful as a marker of treatment. The action of paroxetine may also be associated
      with decreases in IL-8, IL-10, MIP-1beta.

PMID- 19179026
TI  - Do different delivery systems of hormone therapy have different effects on
      psychological symptoms in surgically menopausal women? A randomized controlled
      trial.
AB  - OBJECTIVE: To compare the influence of different delivery forms of estrogen
      therapy on menopausal and psychological symptoms in surgically menopausal women.
      STUDY DESIGN: Surgically menopausal women were assigned to a 1-year-therapy with
      oral conjugated estrogen 0.625mg/day (n=35), intranasal 300microg/day estradiol
      hemihidrate (n=33), percutaneous gel 1.5mg/day estradiol hemihidrate (n=32) or no
      treatment (control group, n=32). Serum E(2) and FSH levels, Kupperman's Scale
      used to assess climacteric symptoms, Hamilton Depression Scale (HDRS) and
      Hamilton Anxiety Rating Scale (HARS) scores were assessed before and after 1-year
      therapy. RESULTS: After 1 year, the greatest increase in E(2) was in the oral
      group, followed by the transdermal gel, and then the intranasal group (oral vs
      transdermal gel: p=0.022: oral vs intranasal: p=0.0001; transdermal gel vs
      intranasal: p=0.0001). All treatment groups improved significantly in total
      Kupperman index score and HARS (p<0.05) with no difference between the groups.
      With regard to HDRS, all treatment groups improved significantly (p<0.05) with
      the greatest improvement in the oral group, and no difference between transdermal
      gel and intranasal groups (oral vs transdermal gel: p=0.015; oral vs intranasal:
      p=0.001; transdermal gel vs intranasal: p=0.735). Control group scored worse in
      all tests after study (p<0.05). All scores correlated significantly with post
      treatment serum E(2) and FSH levels (p<0.001). CONCLUSION: Oral, intranasal and
      percutaneous gel estradiol therapies significantly improve menopausal and
      psychological symptoms in surgically menopausal women with oral route better than
      transdermal gel and intranasal modalities against depressive mood.

PMID- 19179027
TI  - Estimation of the measurement uncertainty of methamphetamine and amphetamine in
      hair analysis.
AB  - The measurement uncertainties (MUs) were estimated for the determination of
      methamphetamine (MA) and its main metabolite, amphetamine (AP) at the low
      concentrations (around the cut-off value of MA) in human hair according to the
      recommendations of the EURACHEM/CITAC Guide and "Guide to the expression of
      uncertainty in measurement (GUM)". MA and AP were extracted by agitating hair
      with 1% HCl in methanol, followed by derivatization and quantification using GC
      MS. The major components contributing to their uncertainties were the amount of
      MA or AP in the test sample, the weight of the test sample and the method
      precision, based on the equation to calculate the mesurand from intermediate
      values. Consequently, the concentrations of MA and AP in the hair sample with
      their expanded uncertainties were 0.66+/-0.05 and 1.01+/-0.06 ng/mg,
      respectively, which were acceptable to support the successful application of the
      analytical method. The method precision and the weight of the hair sample gave
      the largest contribution to the overall combined uncertainties of MA and AP, for
      each.

PMID- 19179028
TI  - Quantitative sonographic measurement of cerebral blood flow volume in infants
      with periventricular leukomalacia.

PMID- 19179029
TI  - Continuously moving table MRI with sliding multislice for rectal cancer staging:
      image quality and lesion detection.
AB  - PURPOSE: To determine image quality and lesion detection of sliding multislice
      (SMS), a recently developed moving table MRI technique, in patients with rectal
      cancer. MATERIALS AND METHODS: Twenty-seven paired SMS (Avanto, Siemens Medical
      Solutions) and MDCT (Sensation 64, Siemens Medical Solutions) examinations of
      abdomen and pelvis were performed in patients with rectal cancer and compared for
      detection of liver, lymph node and bone metastases by two independent observers.
      A contrast-enhanced, fat saturated 2D gradient echo sequence (TE, 2.0 ms; TR, 102
      ms; slice, 5 mm) was acquired with SMS and a standard contrast-enhanced protocol
      (100 ml @ 2.5 ml/s; slice, 5 mm) was used for abdominal MDCT. Standard of
      reference consisted of a consensus evaluation of SMS, MDCT, and all available
      follow-up examinations after a period of 6 months. Artifact burden and image
      quality of SMS was assessed in comparison to stationary gradient echo sequences
      obtained in an age-matched group of 27 patients. RESULTS: Whereas SMS achieved a
      mean quality score of 3.65 (scale, 0-4) for the liver, representing very good
      diagnostic properties, strong breathing artifacts in the intestinal region were
      observed in 19 cases by both observers. The retroperitoneum still achieved a mean
      quality score of 3.52, although breathing artifacts were noted in 12 and 15 cases
      (observers 1 and 2, respectively). The sensitivities of SMS to detect hepatic
      metastases were 91.2% and 94.1% for both observers, respectively, compared to
      98.5%/98.5% for MDCT. The sensitivities for lymph node metastases were
      87.5%/81.3% for SMS compared to 78.1%/81.3% for MDCT. The sensitivities for bone
      metastases were 91.7%/100% for SMS compared to 8.3%/16.7% for MDCT. CONCLUSION:
      With slightly reduced image quality in the intestinal region, SMS exhibits equal
      detection of lymph node and liver metastases compared to MDCT. SMS MRI proved to
      be superior to MDCT in detection of bone metastases.

PMID- 19179030
TI  - Simultaneous determination of sulphamethoxazole and trimethoprim in powder
      mixtures by attenuated total reflection-Fourier transform infrared and
      multivariate calibration.
AB  - A partial least-squares calibration (PLS) procedure in combination with infrared
      spectroscopy has been developed for simultaneous determination of
      sulphamethoxazole (SMZ) and trimethoprim (TMP) in raw material powder mixtures
      used for manufacturing commercial pharmaceutical products. Multivariate
      calibration modeling procedures, interval partial least squares (iPLS) and
      synergy partial least squares (siPLS), were applied to select a spectral range
      that provided the lowest prediction error in comparison to the full-spectrum
      model. The experimental matrix was constructed using 49 synthetic samples and 15
      commercial samples. The considered concentration ranges were 400-900 mg g(-1) SMZ
      and 80-240 mg g(-1) TMP. Spectral data were recorded between 650 and 4000 cm(-1)
      with a 4 cm(-1) resolution by Fourier transform infrared spectroscopy coupled
      with attenuated total reflectance (ATR-FTIR) accessory. The proposed procedure
      was compared with conventional procedure by high performance liquid
      chromatography (HPLC) using 15 commercial samples containing SMZ and TMP. The
      results showed that PLS regression model combined to ATR-FTIR is a relatively
      simple, rapid and accurate procedure that could be applied to the simultaneous
      determination of SMZ and TMP in routine quality control of powder mixtures. A
      root mean square error of prediction (RMSEP) of 13.18 mg g(-1) for SMZ and 6.03
      mg g(-1) for TMP was obtained after selection of better intervals by siPLS. Using
      the proposed procedure it is possible to analyze each sample in less than 3 min
      considering two replicates (excluding the grinding step). Accuracy was checked by
      comparison to HPLC method and agreement better than 98.8% was achieved.

PMID- 19179031
TI  - Characterization and resolution of reversed phase HPLC chromatography failure
      attributed to sulfobutylether-beta-cyclodextrin in a pharmaceutical sample
      preparation.
AB  - A reversed phase HPLC method developed for a drug product formulation using
      hydroxypropyl-beta-cyclodextrin (HPCD) was rendered ineffective for analyzing a
      similar formulation containing sulfobutylether-beta-cyclodextrin (SBECD). The
      active pharmaceutical ingredient (API) and the majority of its impurities became
      more strongly retained, eluting as an incoherent conglomerate of peaks.
      Furthermore, this phenomenon was reproduced in subsequent injections of the API
      reference standard. Based on HPLC and LC-ESI-MS studies, the chromatography
      failure was attributed to the accumulation of SBECD on the HPLC column. The
      subsequent interaction of the API with bound SBECD resulted in the aberrant
      chromatography. An anion-exchange solid-phase extraction treatment was developed
      and qualified to selectively remove SBECD from sample solutions, thereby allowing
      the same HPLC method to be used. The sample treatment procedure exhibited
      suitable accuracy and precision for quantitating the API and its impurities, and
      resulted in typical chromatographic profiles.

PMID- 19179032
TI  - Characterization of increased phenolic compounds from fermented Bokbunja (Rubus
      coreanus Miq.) and related antioxidant activity.
AB  - This study examined the changes in the phenolic acid-content and antioxidant
      activity of Rubi Fructus (RF), the fruit of Rubus coreanus Miq., after
      fermentation with yeast (Saccharomyces cerevisiae). The phenolic acids were
      fractionated into three forms, free (Fr. A), ester (Fr. B), and insoluble-bound
      phenolic acids (Fr. C) and quantified by high performance liquid chromatography
      with a diode array detector (HPLC-DAD). This method was validated and allowed the
      successful identification of 11 phenolic acids in the RF extracts. HPLC-DAD
      analysis of the samples showed substantial increases in the levels of
      protocatechuic, vanillic and p-coumaric acid as the result of yeast fermentation.
      The total phenolic content (TPH) was also increased by fermentation. The total
      phenolics in Fr. A and Fr. B increased from 117 to 173 mg GAE/100 g and from 488
      to 578 mg GAE/100 g, respectively. The total phenolics in Fr. C decreased from
      264 to 175 mg GAE/100 g. The antioxidant activity of the fermented RF was
      measured as the 1,1-diphenoly-2-picrylhydrazyl (DPPH) radical scavenging
      capacity, which is expressed as the IC(50). The IC(50) for Fr. A and Fr. B
      decreased from 5.9 to 4.0 mg/ml (mg of dried RF equiv./ml) and from 1.2 to 0.8
      mg/ml, respectively. In Fr. C, the IC(50) value increased from 2.1 to 2.8 mg/ml.
      In summary, the fermented RF had a higher total phenolic content and better DPPH
      radical-scavenging activity than the unfermented material.

PMID- 19179033
TI  - Effect of Ca2+ on the 1H NMR chemical shift of the methyl signal of oversulphated
      chondroitin sulphate, a contaminant in heparin.
AB  - The chemical shift of the methyl signal of oversulphated chondroitin sulphate
      (OSCS) is dependent on the type and concentration of the counterion. When OSCS is
      present as a contaminant in heparin sodium, the reported methyl 1H chemical shift
      is 2.15 +/- 0.02 ppm. In this report, a value of 2.18 +/- 0.01 ppm is reported
      for the OSCS in the presence of Ca2+. The chemical shift of the methyl signal of
      pure OSCS varies linearly from 2.13 ppm to 2.18 ppm with increasing amounts of
      Ca2+, until reaching the saturation point of four Ca2+ ions per OSCS disaccharide
      unit, which contains four sulphate groups (a 1:1 ratio between sulphate groups
      and Ca2+). This Ca2+ effect can be used for OSCS identification as well as to
      facilitate quantification.

PMID- 19179034
TI  - Changes of serotype and genotype in Streptococcus pneumoniae isolates from a
      Korean hospital in 2007.
AB  - We investigated the change in clones and serotypes of Streptococcus pneumoniae
      isolates in a Korean tertiary-care hospital. Serotypes of S. pneumoniae isolates
      were determined by the capsular quellung method, and in vitro susceptibility
      testing was performed by broth microdilution method. Multilocus sequence typing
      was performed to determine the genotypes of the S. pneumoniae isolates. The
      erm(B) and mef(A) genes in erythromycin-resistant isolates were also detected
      using the duplex polymerase chain reaction method. During the 2 periods assayed
      (1998-2000 and 2007), 7-valent pneumococcal conjugate vaccine (PCV7) serotypes
      decreased significantly from 58.3% to 30.9% (P = 0.001). Especially, serotypes
      19F and 23F decreased significantly from 31.7% to 8.5% (P < 0.0001) and from
      20.0% to 7.4% (P = 0.021), respectively. In contrast to the other PCV7 serotypes,
      serotype 14 coupled with CC554 emerged in 2007, which may indicate no effect of
      PCV7 against serotype 14 isolates from Korea and the possibility of a different
      subtype. Of the non- PCV7 serotypes, serotype 19A increased from 8.3% to 14.9% (P
      = 0.227) and serotype 15 increased from 0% to 8.5% (P = 0.023). The increase of
      serotype 19A was due to the expansion of a preexisting clone with serotype 19A,
      ST320. However, S. pneumoniae isolates of serotype 15 showed diverse STs. Our
      data may provide helpful information in local vaccine serotype expansion or
      replacement in Korea.

PMID- 19179035
TI  - Evaluation of three analyte-specific reagents for detection and typing of herpes
      simplex virus in cerebrospinal fluid.
AB  - The performance of three analyte-specific reagents (ASRs); Cepheid herpes simplex
      virus (HSV) Typing Primer Probe set (CD), Eragen MultiCode-Rtx HSV-1/2 kit primer
      mix (ER), and Roche LightCycler HSV-1/2 Primer/Hybridization Probes (RD), was
      evaluated for detection and typing of herpes simplex virus (HSV-1 and HSV-2) in
      cerebrospinal fluid (CSF) specimens. Of 68 CSF specimens, HSV-1 was detected in 8
      specimens and HSV-2 was detected in 17 specimens. ER detected all 25 HSV-positive
      specimens, whereas CD and RD detected 24 and 23 HSV-positive specimens,
      respectively. The results of HSV typing with the 3 ASRs were in complete
      agreement. The analytical sensitivity of all ASRs was determined to be about
      10(1) copies/reaction. Our results demonstrate that the performances of all 3
      ASRs are comparable and reliable for routine clinical testing in detection and
      typing of HSV DNA in CSF.

PMID- 19179036
TI  - An investigation of the quality of breast cancer information provided on the
      internet by voluntary organisations in Great Britain.
AB  - OBJECTIVE: Patients increasingly use the internet to source health information.
      Voluntary organisations offering information and support often provide such
      information on their websites. However, the internet is unregulated and
      information can be of poor quality. The aim of this study was to evaluate the
      quality of breast cancer information provided by 10 Great Britain (GB) voluntary
      organisations' websites. METHODS: Quality of websites was evaluated using an
      investigator-designed appraisal tool based on European Commission (EC) quality
      criteria for health-related websites. Completeness and transparency of breast
      cancer information, and usability of websites, were appraised. RESULTS:
      Typically, breast cancer-specific organisations provided the highest quality
      information, particularly in terms of its completeness. However, great
      variability in quality was identified. Areas of weakness related to transparency
      of information, in particular disclosure of authorship, and its apparent
      currency. CONCLUSION: Voluntary organisations providing web-based breast cancer
      information have progress to make to ensure information provided is complete and
      transparent, and websites are user-friendly. Unfortunately, informed decision
      making will not be optimised if patients cannot access quality information.
      PRACTICE IMPLICATIONS: Voluntary organisations should regularly review the
      quality of information on their websites. Grading of websites allows healthcare
      professionals to identify and signpost patients to trustworthy, up-to-date
      websites. Thus, ensuring patients receive high quality information.

PMID- 19179037
TI  - A test of the lipostat theory in a seasonal (ovine) model under natural
      conditions reveals a close relationship between adiposity and melanin
      concentrating hormone expression.
AB  - A study was undertaken in Corriedale ewes to test the lipostat theory using data
      obtained from a model of seasonal change in food intake and body composition. The
      theory predicts adipose-derived factors signal to the brain and vice versa, to
      maintain homeostasis. It is held that leptin acts on cells in the brain to
      regulate food intake and energy expenditure, through "first order" neurons in the
      arcuate nucleus (ARC). These cells are thought to receive information that is
      relayed to "second order" neurons, to regulate food intake and other functions.
      In this study, groups (n=4-5) of ovariectomized ewes were maintained under
      natural conditions and sampled at various points across the year. Food intake,
      body composition and indices of metabolic function were measured prior to
      collection of brains for in situ hybridization analysis. Expression of genes
      encoding for neuropeptide Y (NPY), pro-opiomelanocortin (POMC), orexin (ORX),
      melanin concentrating hormone (MCH) and leptin receptor (ObRb) was quantified.
      NPY gene expression was high when food intake was also high but, across the year,
      changes in NPY and POMC gene expression did not correspond predictably to plasma
      leptin levels or leptin receptor gene expression. Negative correlation was found
      between adiposity (omental and whole body fat) and gene expression of MCH and
      ORX, suggesting that changes in expression of genes for "second order" orexigenic
      peptides are closely linked to changes of metabolic state, even when similar
      relationships cannot be shown for expression of genes in "first order" neurons.
      These data provide support for the lipostat theory.

PMID- 19179038
TI  - Increased GH secretion in scrapie, a prion-associated neurodegenerative disease,
      is not due to suppressed IGF-1 negative feedback.
AB  - GH secretion is increased in scrapie-diseased sheep. Although the role of the
      somatotropic axis as a neurotrophic and neuroprotective factor is well
      documented, no studies have been carried out on the mechanisms and functional
      significance of somatotropic perturbation in the pathophysiology of prion
      associated neurodegenerative disease. The goal of this study was to test the
      hypothesis that increased GH secretion observed in a natural animal prion
      disease, scrapie, might reflect a general lack of action of IGF-1 and, more
      particularly, a suppressed IGF-1 negative feedback. The effect of human
      recombinant IGF-1 (rhIGF-1) on spontaneous and GHRH-induced secretions was
      studied in so-called "scrapie-resistant" and "scrapie sensitive" rams in vivo and
      in vitro on pituitary dissociated cells from both groups. The effect of rhIGF-1
      infusion on spontaneous and GHRH-induced GH secretions was evaluated during the
      preclinical and clinical stages of the disease in vivo. Our results indicated
      that rhIGF-1 suppressed spontaneous GH secretion but not GHRH-induced secretion
      in vivo. RhIGF-1 had no effect on spontaneous and GHRH-induced GH secretion from
      dissociated pituitary cells. Clinical scrapie was associated with a significantly
      greater rhIGF-1-induced inhibition of GH spontaneous secretion (mean+/-S.E.M.
      inhibition of GH secretion: 31+/-8% vs. 45+/-4% in control and scrapie-affected
      rams, respectively). It can be concluded that the increase in GH secretion in
      scrapie-affected animals does not reflect a global lack of action of IGF-1.
      Further investigations are required to determine if other IGF-1 effects and more
      particularly neuroprotective mechanisms are altered in prion-associated
      neurodegenerative diseases.

PMID- 19179039
TI  - The role of serum CA-125 levels in early-stage epithelial ovarian cancer on
      preoperative CT and MRI.
AB  - BACKGROUND: We sought to identify the role of serum CA-125 levels in early-stage
      epithelial ovarian cancer (EOC) on preoperative CT and MRI. METHODS: Clinical
      data of 101 patients with early-stage EOC on preoperative CT and MRI were
      collected between January 2000 and December 2007. Clinical stage I (n=59) was
      defined as tumor limited to the ovaries with or without ascites, whereas clinical
      stage II (n=42) was defined as tumor within the pelvis with or without ascites.
      The primary endpoint was to investigate the efficacy of serum CA-125 levels for
      the prediction of advanced-stage disease, and secondary endpoints were to
      evaluate the accuracy of preoperative CT and MRI, and to examine the role of
      serum CA-125 levels as a prognostic factor for survival. RESULTS: The results of
      preoperative CT and MRI were concordant with no peritoneal implants outside the
      pelvis in 50/101 (50%) and no lymph node metastasis in 71/101 (70%) patients. The
      receiver operating characteristic curves showed that best cut-off values of serum
      CA-125 levels were 320 U/ml (71% sensitivity, 84% specificity) and 510 U/ml (67%
      sensitivity, 80% specificity) for the prediction of peritoneal implants outside
      the pelvis and lymph node metastasis. The serum CA-125 level (> or =320 U/ml) was
      a significant factor for the prediction of advanced-stage disease (adjusted OR,
      7.43; 95% CI, 2.39-23.04). However, it was not an independent prognostic factor
      for survival. CONCLUSIONS: Serum CA-125 levels may be very useful for the
      prediction of advanced-stage disease in early-stage EOC on preoperative CT and
      MRI.

PMID- 19179040
TI  - An outbreak of body weight dissatisfaction associated with self-perceived BMI and
      dieting among female pharmacy students.
AB  - Some reports indicate that in various groups of society living in the highly
      developed countries a body weight perception and weight satisfaction tend to be
      inappropriate when compared with body mass index (BMI) calculated from estimated
      actual weight and height. Thus in present studies a relationship between body
      weight perceptions, measured actual BMI, gender, and dieting practices in a
      sample population of pharmacy students in Poland were examined to verify
      hypothesis that their incorrect self-perception would provoke occasional,
      seasonal and permanent eating disorders. Height and weight data of 178 pharmacy
      students (mean age 22.6+/-2.4 years) in Bydgoszcz, Poland, were collected and
      validated by completed self-reported questionnaire assessing their self-perceived
      body weight, desired body weight and past/current dieting practices. Only 34.4%
      of female and 37.1% of male pharmacy students was satisfied with their current
      body weight. Statistical analyses revealed significant differences in estimated
      BMI status (chi(2)=28.5; p=0.0001), desired body weight (chi(2)=15.6; p=0.0004)
      and past dieting (chi(2)=7.6; p=0.0050) by gender. In the male sub-group of
      students (n=27) unclear association (chi(2)=6.1; p=0.046) between measured actual
      BMI status and self-perceived body weight have been presented. Moreover, in male
      students a significant relationship (chi(2)=4.9; p=0.0261) between actual BMI
      status and both past as well as current weight control behavior in the form of
      dieting practices was exhibited. In case of a sub-group of female students
      (n=151) a diffuse association of actual BMI and self-perception of their body
      weight (chi(2)=69.5; p=0.0001) was obtained. However, a close relation
      (chi(2)=16.9; p=0.0007) between actual BMI and only past dieting practices was
      observed in females. Furthermore, in this last sub-group of students the
      significant relationship (chi(2)=53.9; p=0.0001) between measured actual BMI and
      desired body weight was also demonstrated. The study showed an evidence of
      distorted self-perception of body weight in both sub-groups of considered
      pharmacy students. There was a tendency to overestimate of body weight in female
      students, and to underestimate in male students. These results suggest common
      dissatisfaction of body weight, especially among females, who were more often
      engaged in dieting, despite not being overweight or obese according to measured
      actual BMI status.

PMID- 19179041
TI  - Revascularization of a specific angiosome for limb salvage: does the target
      artery matter?
AB  - Ischemic wounds of the lower extremity can fail to heal despite successful
      revascularization. The foot can be divided into six anatomic regions (angiosomes)
      fed by distinct source arteries arising from the posterior tibial (three),
      anterior tibial (one), and peroneal (two) arteries. This study investigated
      whether bypass to the artery directly feeding the ischemic angiosome had an
      impact on wound healing and limb salvage. Retrospective analysis was performed
      for 52 nonhealing lower extremity wounds (48 patients) requiring tibial bypass
      over a 2-year period. Preoperative arteriograms were reviewed to determine
      arterial anatomy relative to each wound's specific angiosome and bypass anatomy.
      Patients were divided into two groups; direct revascularization (DR, bypass to
      the artery directly feeding the ischemic angiosome) or indirect revascularization
      (IR, bypass unrelated to the ischemic angiosome). Wound outcome was analyzed with
      regard to the endpoints of complete healing, amputation, or death unrelated to
      the wound. Time to healing was also noted for healed wounds. Based on
      preoperative arteriography, 51% (n = 27) of the wounds received DR to the
      ischemic angiosome, while 49% (n = 25) underwent IR. There were no statistically
      significant differences in the comorbidities of the two groups. Revascularization
      was via tibial bypass using the saphenous vein (n = 34, 65%) or
      polytetrafluoroethylene with a distal vein patch (n = 18, 35%). Bypasses were
      performed to the anterior tibial (n = 22, 42%), posterior tibial (n = 17, 33%),
      or peroneal (n = 13, 25%) arteries based on the surgeon's judgment. One bypass
      failed in the perioperative period and was excluded from the analysis. The
      remaining bypasses were patent at the time of wound analysis. Due to a 17%
      mortality rate during follow-up, 43 wounds were available for endpoint analysis.
      This analysis demonstrated that 77% of wounds (n = 33) progressed to complete
      healing and 23% of wounds (n = 10) failed to heal with resultant amputation. In
      the DR group, there was 91% healing with a 9% amputation rate. In the IR group,
      there was 62% healing with a 38% amputation rate (p = 0.03). In those wounds that
      did heal, total time to healing was not significantly different--DR 162.4 days
      versus IR 159.8 days (p = 0.95). Revascularization plays a crucial role in the
      treatment of ischemic lower extremity wounds. We believe that direct
      revascularization of the angiosome specific to the anatomy of the wound leads to
      a higher rate of healing and limb salvage. Although many factors must be
      considered in choosing the target artery for revascularization, consideration
      should be given to revascularization of the artery directly feeding the ischemic
      angiosome.

PMID- 19179042
TI  - Pyoderma gangrenosum after lower extremity bypass.
AB  - A 66-year-old male with lower extremity ischemia underwent femoral-posterior
      tibial bypass with composite vein graft from the arm. Ten days later, he
      presented to the emergency department with pain, wound erythema, and drainage.
      Despite a prolonged course of intravenous antibiotics and serial operative
      debridements, the wound edges repeatedly necrosed after each procedure. The vein
      graft remained viable. Punch biopsies of wound edges were consistent with
      pyoderma gangrenosum (PG). The patient's condition improved on immunosuppressive
      therapy. Although a rare clinical entity, postsurgical PG is a well-described
      phenomenon whose diagnosis is often delayed. Clinical suspicion is imperative to
      ensure timely treatment and minimize morbidity.

PMID- 19179043
TI  - Indirect comparison: relative risk fallacies and odds solution.
AB  - OBJECTIVE: When undertaking indirect comparisons, relative risk (RR) is often
      suggested as an appropriate indicator of treatment effect, particularly where
      baseline (common comparator) risks differ. In this article, we demonstrate that
      such use of RR in indirect comparisons is not necessarily stable with respect to
      framing of outcomes. STUDY DESIGN AND SETTING: Use of RR is shown to lead to
      inferential fallacies where, for example, a new therapy is suggested to reduce
      both mortality and survival risk. Conditions under which the inferential fallacy
      arises and an odds solution are illustrated in indirect comparison of natalizumab
      and interferon beta-1b for multiple sclerosis. RESULTS: Using RR, natiluzimab is
      suggested to be 30% more effective than interferon for progression (RR=0.70), but
      16% less effective than interferon for no progression (RR=0.84). This inferential
      anomaly is avoided using odds ratios (ORs), with odds of progression (0.83) the
      reciprocal of that for no progression (1.21). CONCLUSION: Inferential fallacies
      with use of RR in indirect comparison provide scope for abuse with respect to
      choice in framing of outcomes, and confound decision making where both results
      are presented. The use of ORs overcomes this inferential fallacy, consistently
      informing inference with respect to direction of treatment effect in indirect
      comparisons.

PMID- 19179044
TI  - Boron neutron capture therapy for papillary cystadenocarcinoma in the upper lip:
      a case report.
AB  - Boron neutron capture therapy (BNCT) is a tumor-selective radiation therapy using
      alpha and (7)Li particles, which are produced by the reaction of neutron with
      boron ((10)B), and taken up by the tumor. The authors report their first
      experience of BNCT on a patient with no history of surgery, chemotherapy or
      conventional radiotherapy for papillary cystadenocarcinoma in the upper lip.

PMID- 19179045
TI  - Traumatic pseudolipoma: herniation of buccal fat pad, a report of two cases.
AB  - Traumatic pseudolipoma is a term used to describe intra-oral herniation of the
      buccal fat pad. A tear of the buccinator muscle and buccal mucosa allows the
      buccal fat pad to extrude into the oral cavity. Initially, the lesion can suggest
      a more sinister cause, but a history of trauma, an absence of mass before the
      accident, anatomical site and fatty appearance should suggest a diagnosis of
      traumatic herniation of buccal fat pad. This injury is rare, but two cases
      presented to the authors' hospital over a period of 3 months.

PMID- 19179046
TI  - A selective laser sintering guide for transferring a virtual plan to real time
      surgery in composite mandibular reconstruction with free fibula osseous flaps.
AB  - The free fibular flap is the standard procedure for reconstructing mandibular
      defects. The graft has to be contoured to fit the defect so preoperative planning
      is required. The systems used previously do not allow transfer of the surgical
      plan to the operation room in an optimal way. The authors present a method to
      bring the virtual plan to real time surgery using a rapid prototyping guide.
      Planning was conducted using the Surgicase CMF software simulating surgery on a
      workstation. The osteotomies were translated into a rapid prototyping guide,
      sterilised and applied during surgery on the fibula allowing for the osteotomies
      and osteosynthesis to be performed with intact circulation. During reconstruction
      the authors were able to choose the best site for the osteotomies regarding
      circulation and as a result increased the precision and speed of treatment.

PMID- 19179047
TI  - Usefulness of a 1.5 T MRI-compatible EEG electrode system for routine use in the
      intensive care unit of a tertiary care hospital.
AB  - BACKGROUND: Continuous electroencephalogram (cEEG) recordings are being
      increasingly used in intensive care units (ICUs) to detect epileptic seizures and
      other changes. MRI scans can interrupt such recordings if the EEG electrodes need
      to be removed and important data can be missed. METHODS: We retrospectively
      examined EEG recordings from ICU patients who underwent MRI scans, comparing
      those from patients with the MRI-compatible EEG electrodes with those who had to
      have the EEG electrodes removed before scanning. We also examined technical
      aspects of the recording and scalp abrasions in both groups. RESULTS: Fourteen of
      31 (45%) EEG recordings with the MRI-compatible electrode system in patients that
      underwent MRI scans between 03:00 p.m. and 07:00 a.m. (when technologists were
      not available) captured seizures. In contrast, all of the six EEG recordings with
      the MRI-incompatible electrode system in patients that underwent MRI scanning
      during the same interval were interrupted and had no data. Recording
      characteristics of the EEGs were comparable between the two groups and none had
      scalp abrasions. CONCLUSION: A significant proportion of patients undergoing MRI
      scans with the MRI-compatible EEG electrodes had seizures that would have been
      missed if the MRI-incompatible EEG electrodes had been used.

PMID- 19179048
TI  - Heart rate variability response to mental arithmetic stress is abnormal in first
      degree relatives of individuals with schizophrenia.
AB  - BACKGROUND: Schizophrenia patients exhibit an abnormal autonomic response to
      mental stress. We sought to determine the cardiac autonomic response to mental
      arithmetic stress in their unaffected first-degree relatives. METHODS: Heart rate
      variability (HRV) analysis was performed on recordings obtained before, during,
      and after a standard mental arithmetic task to induce mental stress. 22
      unaffected first-degree relatives of patients meeting DSM-IV criteria for
      schizophrenia (R) and 22 healthy individuals (C) were included in this study.
      RESULTS: Patients' relatives (R) had a normal response to the mental arithmetic
      stress test, showing an increased heart rate compared with controls. They also
      displayed the characteristic pattern of relative contributions of HRV components
      that consists of increased low-frequency (LF) HRV and decreased high-frequency
      (HF) HRV. Recovery of the resting pattern of HRV immediately after stress
      termination was observed in healthy subjects (LF 62+/-16% vs. 74+/-10% , HF 37+/
      16% vs. 25+/-10%, F=9.616, p=0.004), but not in patients' relatives (LF 60+/-19%
      vs. 70+/-13%, HF 40+/-19% vs. 29+/-13%, F=8.4, p=0.056). CONCLUSIONS: First
      degree relatives of schizophrenia patients exhibit an abnormal pattern of
      protracted response to mental arithmetic stress, though less intense than that
      observed in patients in a previous study. This suggests that a pattern of
      autonomic response to stress may therefore be familial and heritable.

PMID- 19179049
TI  - Long-term stability of measuring D(2) receptors in schizophrenia patients treated
      with antipsychotics.
AB  - BACKGROUND: While antipsychotic-free schizophrenia patients showed a high degree
      of within-subject variability in dopamine D(2) receptor density over 6-24 months,
      no study has examined the long-term stability of D(2) receptor measures in
      medicated patients. METHODS: Four schizophrenia patients receiving a stable dose
      of risperidone underwent [(11)C]raclopride positron emission tomography scans on
      two occasions 5-14 months apart. RESULTS: Plasma risperidone levels were found to
      be consistent between scans, and consistencies of nondisplaceable D(2) binding
      potential and D(2) occupancy were good. CONCLUSIONS: The finding supports the
      validity of quantification of D(2) receptor binding in longitudinal PET studies
      of medicated patients with schizophrenia.

PMID- 19179050
TI  - Abnormal prefrontal cortical activity and connectivity during response selection
      in first episode psychosis, chronic schizophrenia, and unaffected siblings of
      individuals with schizophrenia.
AB  - The search for genes conferring liability for schizophrenia may be aided by the
      identification of endophenotypes. Response selection is a heritable cognitive
      function that is impaired in patients with schizophrenia and their unaffected
      siblings. The abnormalities in cerebral function that presumably underlie the
      deficit in patients and unaffected siblings remain to be elucidated. Cerebral
      neurophysiology during performance of a 4-choice reaction time (CRT) task in 25
      patients with schizophrenia (15 medication free first episode (FEP) and 10
      chronic patients), 32 controls, and 12 unaffected siblings of individuals with
      schizophrenia was investigated using fMRI. CRT was impaired in both medication
      free FEP and chronic patients with schizophrenia, and unaffected siblings. FEP
      patients, chronic patients, and unaffected siblings demonstrated greater BOLD
      response in the right dorsolateral prefrontal cortex (dlPFC) during CRT task
      blocks. The nature of the altered activation in the dlPFC was further examined
      using functional connectivity analysis. This revealed marked reductions in
      connectivity between the right dlPFC and multiple brain regions in both patient
      groups and, to a lesser degree, unaffected siblings. The magnitude of
      connectivity between right dlPFC and inferior parietal lobule correlated with
      task performance in the combined patient/unaffected siblings group, but not
      controls suggesting that the network of brain regions recruited to perform the
      task differed as a function of genetic liability for schizophrenia. The findings
      suggest that altered activity and connectivity of the right dlPFC appears to be
      related to genetic vulnerability for schizophrenia and may represent a potential
      endophenotype of the disorder.

PMID- 19179051
TI  - Identification and characterisation of a novel antimicrobial polypeptide from the
      skin secretion of a Chinese frog (Rana chensinensis).
AB  - Amphibians secrete small antimicrobial polypeptides from their skin that have
      been explored as alternatives to conventional antibiotics. In this study, mass
      spectrometry was used to identify and characterise protein secretions from the
      skin of a Chinese frog, Rana chensinensis. The skin of this kind of frog has been
      used in traditional Chinese medicine for centuries as a remedy against
      inflammation. A novel antimicrobial peptide was identified and the
      characteristics of this peptide were analysed using far-ultraviolet circular
      dichroism. When dissolved in aqueous solution, the peptide displayed a high level
      of random coil structure, in contrast to a more ordered alpha-helical structure
      when dissolved in 50% trifluoroethanol. Functional studies showed that this
      peptide has potent antimicrobial activity both against Gram-positive and Gram
      negative bacteria and has extremely low haemolytic activity to human red blood
      cells. Taken together, these studies suggest that this novel peptide can be
      further developed as an antimicrobial agent.

PMID- 19179052
TI  - Probiotics for the prevention of respiratory tract infections: a systematic
      review.
AB  - We evaluated the clinical evidence regarding probiotic use for the prevention of
      respiratory tract infections (RTIs). Randomised controlled trials (RCTs) studying
      the effects of probiotics for the prevention of upper or lower RTIs were
      systematically identified. Fourteen RCTs (twelve involving healthy subjects and
      two involving patients with RTIs) were included. Various Lactobacillus strains
      were used in seven RCTs, combinations of Lactobacillus and Bifidobacterium
      strains were used in five RCTs, and a Bifidobacterium strain and a non-pathogenic
      Enterococcus faecalis strain were used in one RCT, respectively. In ten RCTs no
      difference was found regarding the incidence of RTIs in the probiotic arm
      compared with the control arm, whereas the remaining four RCTs favoured the use
      of probiotics. Reduction in the severity of symptoms related to RTIs was noted in
      five of six RCTs that provided relevant data. In three of nine RCTs that provided
      relevant data, the clinical course of RTIs was shorter in the probiotic arm,
      whereas no difference was found in the remaining six RCTs. In conclusion,
      probiotics may have a beneficial effect on the severity and duration of symptoms
      of RTIs but do not appear to reduce the incidence of RTIs.

PMID- 19179053
TI  - Inhibitory efficacy of various antibiotics on matrix and viable mass of
      Staphylococcus aureus and Pseudomonas aeruginosa biofilms.
AB  - Both bacteria and the matrix are essential for the development of biofilms.
      Antimicrobials should therefore be tested against both components. The aim of
      this study was to determine the structure-activity relationships of different
      antibiotics against biofilm-forming Staphylococcus aureus and Pseudomonas
      aeruginosa strains using in vitro biofilm discriminatory assays. Only four of
      twelve antibiotics showed efficacy against S. aureus biofilms. Rifampicin had a
      50% inhibitory activity both against the matrix and bacteria at 16 x the minimum
      bactericidal concentration (MBC). Polymyxin B killed nearly all bacteria at 8 x
      MBC, but left the matrix undisturbed. Both P. aeruginosa biofilms responded
      differently to antibiotic treatment. Rifampicin showed the greatest activity,
      with 100% killing of microorganisms combined with 91% destruction of the matrix
      at the MBC. In conclusion, rifampicin showed the highest activity on biofilm
      matrix and bacteria in S. aureus and P. aeruginosa biofilms. Our results also
      indicated that biofilm viable mass was more susceptible to treatment than the
      biofilm matrix, which is mainly responsible for biofilm persistence. Future
      research should specifically focus on compounds destroying the matrix that can be
      used as an adjunct to antibiotic therapy.

PMID- 19179055
TI  - Interhemispheric propagation time and temporal lobe epileptogenicity.
AB  - Long-term subdural electroencephalographic (EEG) recording was performed in a
      series of patients with medically intractable complex partial seizures to test
      the hypothesis that ictal interhemispheric propagation time (IHPT) is correlated
      with temporal lobe epileptogenicity. In 41 patients, the duration from initial
      subdural EEG seizure onset to the first appearance of subdural EEG epileptic
      activity in the contralateral hemisphere (IHPT) was measured in seconds and
      analyzed for a quantitative relationship to temporal lobe seizure interval
      (frequency-1), in hours. A statistically significant, nonlinear correlation
      between IHPT and seizure interval was found (Arctan y=-0.009x2+0.598x+75.187,
      y=IHPT, in seconds, x=seizure interval, in hours, r=0.326, d.f.=39, t=2.15,
      p<0.05). The results suggest that, for seizure intervals less than 33h,
      increasing IHPT is associated with increasing seizure interval (i.e. decreasing
      epileptogenicity). Conversely, for seizure intervals greater than 33h, decreasing
      IHPT is associated with increasing seizure interval. Because the relationship
      between IHPT and seizure interval is a trigonometric (i.e. arctangent) function
      of a second degree polynomial, small changes in IHPT are associated with
      substantial changes in seizure interval. These findings suggest that temporal
      lobe epileptogenicity is a complex, nonlinear function of the
      electrocorticographic EEG time factor (i.e. IHPT) involved in the transmission of
      ictal epileptic activity from the seizure focus to the contralateral hemisphere.
      The results suggest that, on an electrophysiologic basis, patients with temporal
      lobe epilepsy represent two distinct populations based on seizure interval. The
      results should improve the understanding of the electrocorticographic
      pathophysiology of temporal lobe epilepsy. The development of cortical
      neuromodulation strategies designed to suppress temporal lobe seizures should
      consider this complex relationship between temporal lobe interhemispheric
      propagation time and epileptogenicity.

PMID- 19179056
TI  - [Impact of very preterm birth on visuospatial processes at 5 years of age].
AB  - OBJECTIVE: Very preterm children can experience cognitive and behavioral
      difficulties. The aim of this study was to assess the impact of very preterm
      birth on visuospatial processes at preschool age. DESIGN AND METHODS: Data come
      from the Epipage study. Participants underwent a follow-up evaluation at age 5
      years. During the psychological evaluation, children took subtests of the K-ABC
      and the WPPSI-R. Six subtests are based on visuospatial information. RESULTS: The
      results concern 183 children assessed in the Lorraine region of France, who were
      born with birthweight appropriate for gestational age and had no neurological
      sequelae. Thirty-six children were born at term, 112 were born very prematurely
      (28-32 GW), and 35 were born extremely prematurely (<28 GW). Birth term was
      significantly correlated with performance on the six subtests. In all cases, the
      children born at term obtained higher scores compared to the children born very
      prematurely and extremely prematurely. On two subtests of the K-ABC, the children
      born extremely prematurely obtained lower scores than those of the children born
      very prematurely. The mother's level of education was correlated with performance
      on three subtests. CONCLUSION: The results suggest that a very preterm birth can
      exert a negative impact on visuospatial and visuomotor processes. These deficits
      may involve difficulties in some activities at school and in daily life.

PMID- 19179054
TI  - Biochemical abnormalities of the medial temporal lobe and medial prefrontal
      cortex in late-life depression.
AB  - We utilized single-voxel (1)H magnetic resonance spectroscopy (MRS) to
      investigate biochemical abnormalities related to late-life depression in the
      medial prefrontal cortex and medial temporal lobe. Fourteen elderly subjects
      whose depression responded to treatment and 12 nondepressed subjects were
      enrolled. Subjects were scanned using a GE 3.0 Tesla whole body MR scanner.
      Metabolite concentrations were quantified using the LC Model software and
      adjusted for CSF and ratio of gray to white matter. ANCOVA models tested for
      group differences while controlling for age and sex. Older previously depressed
      individuals showed significantly reduced concentrations of total N-acetyl
      aspartate (NAA), choline, and creatine in the prefrontal cortex and significantly
      elevated left medial temporal lobe concentrations of NAA and myo-inositol. There
      were no significant group differences in right temporal metabolite
      concentrations. The prefrontal cortex observations suggest that reduced neuronal,
      phospolipid, and energy metabolism is present even in clinically improved
      depression. In contrast, elevated NAA and myo-inositol concentrations in the left
      medial temporal lobe could be associated with neuronal and glial cell changes in
      the amygdala.

PMID- 19179057
TI  - [The French-Speaking Pediatric Research Society: in danger of extinction?].

PMID- 19179058
TI  - A high menaquinone intake reduces the incidence of coronary heart disease.
AB  - BACKGROUND AND AIM: Vitamin K dependent proteins have been demonstrated to
      inhibit vascular calcification. Data on the effect of vitamin K intake on
      coronary heart disease (CHD) risk, however, are scarce. To examine the
      relationship between dietary vitamins K(1) and K(2) intake, and its subtypes, and
      the incidence of CHD. METHODS AND RESULTS: We used data from the Prospect-EPIC
      cohort consisting of 16,057 women, enrolled between 1993 and 1997 and aged 49-70
      years, who were free of cardiovascular diseases at baseline. Intake of vitamin K
      and other nutrients was estimated with a food frequency questionnaire.
      Multivariate Cox proportional hazards models were used to analyse the data. After
      a mean+/-SD follow-up of 8.1+/-1.6 years, we identified 480 incident cases of
      CHD. Mean vitamin K(1) intake was 211.7+/-100.3 microg/d and vitamin K(2) intake
      was 29.1+/-12.8 microg/d. After adjustment for traditional risk factors and
      dietary factors, we observed an inverse association between vitamin K(2) and risk
      of CHD with a Hazard Ratio (HR) of 0.91 [95% CI 0.85-1.00] per 10 microg/d
      vitamin K(2) intake. This association was mainly due to vitamin K(2) subtypes MK
      7, MK-8 and MK-9. Vitamin K(1) intake was not significantly related to CHD.
      CONCLUSIONS: A high intake of menoquinones, especially MK-7, MK-8 and MK-9, could
      protect against CHD. However, more research is necessary to define optimal intake
      levels of vitamin K intake for the prevention of CHD.

PMID- 19179059
TI  - Effects of maternal dietary manipulation during different periods of pregnancy on
      hepatic glucogenic capacity in fetal and pregnant rats near term.
AB  - BACKGROUND AND AIM: Low birth weight is associated with an increased incidence of
      adult glucose intolerance, type 2 diabetes and cardiovascular disease in humans.
      In pregnant rats, dietary calorie or protein deprivation results in growth
      retarded pups, which become glucose intolerant adults with abnormal hepatic
      glucose metabolism and gluconeogenic enzyme activities. However, whether these
      abnormalities are present before birth remain unknown. METHODS AND RESULTS: This
      study examined the effects of manipulating dietary protein and carbohydrate
      intake during rat pregnancy on the fetal and maternal hepatic activities of the
      gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate
      carboxykinase (PEPCK). Wistar rats were fed ad libitum with either standard chow
      throughout pregnancy (25% protein, 57% carbohydrate, n=6) or an isocaloric, low
      protein, high carbohydrate diet (LPHC, 8% protein, 81% carbohydrate) for
      different periods of pregnancy (early, 0-10 days, n=6; late, 10-20 days, n=7;
      throughout, 0-20 days, n=6) before tissue collection at day 20. The LPHC diet had
      no effect on fetal or placental weights, or on fetal hepatic activities of G6Pase
      and PEPCK in the early LPHC group. In contrast, fetuses of dams fed the LPHC diet
      in late or throughout pregnancy had lower body and placental weights, and higher
      hepatic G6Pase and PEPCK activities than controls. Maternal hepatic G6Pase
      activity was elevated in all LPHC groups, while maternal PEPCK activity was only
      increased significantly in the late LPHC group. CONCLUSIONS: Feeding a LPHC diet,
      particularly during late pregnancy, therefore, up-regulates fetal and maternal
      hepatic glucogenic capacity.

PMID- 19179060
TI  - High protein diets decrease total and abdominal fat and improve CVD risk profile
      in overweight and obese men and women with elevated triacylglycerol.
AB  - BACKGROUND AND AIMS: It is unclear whether high protein weight loss diets have
      beneficial effects on weight loss, abdominal fat mass, lipids, glucose and
      insulin compared to conventional low fat diets in subjects at increased risk of
      cardiovascular disease (CVD) because of elevated glucose and triglyceride
      concentrations. Our objective was to determine the effects of high protein (HP)
      compared to standard protein (SP) diets on CVD risk in obese adults. METHODS AND
      RESULTS: Data from three, 12 week, randomized parallel trials with subjects
      assigned to either HP or SP diet (5500-6500 kJ/day) were pooled. Weight, body
      composition (dual energy X-ray absorptiometry), lipids, insulin and glucose were
      measured before and after weight loss. Data from 215 subjects (49.9+/-9.8 years,
      BMI 33.5+/-3.7 kg/m(2)), 108 HP, 107 SP were analyzed. Weight loss (HP diet
      7.82+/-0.37 kg; SP diet 7.65+/-0.39 kg, NS) and total fat loss were not different
      (HP 6.8+/-4.3 kg; LP 6.4+/-4.7 kg, NS on intention to treat analysis). The
      reduction in triacylglycerol (TAG) was greater on HP than SP 0.48+/-0.07 mmol/L
      vs 0.27+/-0.06 mmol/L, (P<0.001). Subjects with TAG greater than the median
      (>1.54 mmol/L at baseline) lost more weight (HP 8.5+/-0.6; SP 6.9+/-0.6 kg,
      P=0.01, diet by TG group), total (HP 6.17+/-0.50 kg; SP 4.52+/-0.52 kg, P=0.007)
      and abdominal fat (HP 1.92+/-0.17 kg; SP 1.23+/-0.19 kg, P=0.005) on HP. Total
      cholesterol (12 vs 6%, HP vs SP) and TAG (39 vs 20%, HP vs SP) decreased to a
      greater extent in these subjects (both P</=0.05) on HP. CONCLUSION: Short-term
      high protein weight loss diets had beneficial effects on total cholesterol and
      triacylglycerol in overweight and obese subjects and achieved greater weight loss
      and better lipid results in subjects at increased risk of CVD. These observations
      provide further information regarding the utility of this dietary approach in
      effectively managing body weight and composition and reducing CVD risk in
      overweight and obese individuals.

PMID- 19179061
TI  - Subacute and chronic hypersensitivity pneumonitis: histopathological patterns and
      survival.
AB  - BACKGROUND: In hypersensitivity pneumonitis (HP), survival can be predicted on
      the basis of the severity of fibrosis in surgical lung biopsy, but few data are
      available on the influence of clinical, functional, tomographic and histologic
      findings on prognosis. OBJECTIVES: To describe the impact on survival of clinical
      data, histological patterns, and HRCT findings in subacute/chronic HP. METHODS: A
      retrospective analysis of 103 patients diagnosed with HP submitted to surgical
      lung biopsy. Chronic HP was characterized by HRCT findings indicative of fibrosis
      (n=76). RESULTS: The most relevant exposures were to molds and birds. Lung
      biopsies revealed typical HP with granulomas in 46 patients, bronchiolocentric
      interstitial pneumonia in 27, and non-specific interstitial pneumonia (NSIP) in
      16. By univariate analysis, several findings were predictors of mortality: older
      age, male sex, velcro crackles, higher FEV(1)/FVC ratio, lower oxygen saturation
      during exercise, and absence of mosaic pattern/air trapping and presence of
      fibrosis on HRCT. By multivariate analysis, remained significant: age (p=0.007),
      oxygen saturation during exercise (p=0.003), and mosaic pattern/air trapping on
      HRCT (p=0.004). Patients with NSIP had a greater survival than did those with
      typical histology and those with bronchiolocentric pneumonia (p=0.033).
      CONCLUSIONS: A wide range of histological features are found in HP. Typical
      findings are seen in 45% of cases. Other common patterns are NSIP and
      centriacinar lesions. Survival is better in patients with NSIP and worse in those
      with older age, desaturation during exercise, and absence of mosaic pattern/air
      trapping on HRCT.

PMID- 19179062
TI  - Cost minimization analysis for combinations of sampling techniques in
      bronchoscopy of endobronchial lesions.
AB  - BACKGROUND: The choice of sampling techniques in bronchoscopy with sampling from
      a visible lesion will depend on the expected diagnostic yields and the costs of
      the sampling techniques. AIMS: The aim of this study was to determine the most
      economical combination of sampling techniques when approaching endobronchial
      visible lesions. METHODS: A cost minimization analysis was performed. All
      bronchoscopies from 2003 and 2004 at Haukeland university hospital, Bergen,
      Norway, were reviewed retrospectively for diagnostic yields. 162 patients with
      endobronchial disease were included. Potential sampling techniques used were
      biopsy, brushing, endobronchial needle aspiration (EBNA) and washings. Costs were
      estimated based on registration of equipment costs and personnel costs.
      Sensitivity analyses were performed to determine threshold values. RESULTS: The
      combination of biopsy, brushing and EBNA was the most economical strategy with an
      average cost of Euro 893 (95% CI: 657, 1336). The cost of brushing had to be
      below Euro 83 and it had to increase the diagnostic yield more than 2.2%, for
      biopsy and brushing to be more economical than biopsy alone. The combination of
      biopsy, brushing and EBNA was more economical than biopsy and brushing when the
      cost of EBNA was below Euro 205 and the increase in diagnostic yield was above
      5.2%. CONCLUSION: In the current study setting, biopsy, brushing and EBNA was the
      most economical combination of sampling techniques for endobronchial visible
      lesions.

PMID- 19179064
TI  - Modifications of p53: competing for the lysines.
AB  - The p53 tumour suppressor protein is subject to numerous post-translational
      modifications, which coalesce in various combinations and patterns to regulate
      its activity. In addition to a multitude of phosphorylated serines and
      threonines, many of the lysine residues in p53 can be modified to regulate
      activity, stability and subcellular localization of the protein. This complexity
      is amplified by the variety of modifications that can target the same lysine
      residue - often with opposing effects on p53 function.

PMID- 19179063
TI  - Walking the walk: how kinesin and dynein coordinate their steps.
AB  - Molecular motors drive key biological processes such as cell division,
      intracellular organelle transport, and sperm propulsion and defects in motor
      function can give rise to various human diseases. Two dimeric microtubule-based
      motor proteins, kinesin-1 and cytoplasmic dynein can take over one hundred steps
      without detaching from the track. In this review, we discuss how these processive
      motors coordinate the activities of their two identical motor domains so that
      they can walk along microtubules.

PMID- 19179065
TI  - Regulation by c-Myc of ncRNA expression.
AB  - Deregulated activity of the proto-oncogene product c-Myc is instrumental in
      promoting many human cancers. As it is a transcription factor, priority has been
      given to identifying the genes that it regulates. Until recently, all the
      attention was focused on protein-encoding genes. It is now clear, however, that c
      Myc also controls the production of many non-coding (nc) RNAs, including tRNA,
      rRNA and miRNAs. This involves it regulating the transcriptional activity of
      three different RNA polymerases. These ncRNAs are likely to contribute
      substantially to the complex biology and pathology that is associated with c-Myc.

PMID- 19179066
TI  - Down-regulation of K-ras and H-ras in human brain gliomas.
AB  - Ras genes, a class of nucleotide-binding proteins that regulate normal and
      transformed cell growth, have been scarcely investigated in human brain tumours.
      We evaluated the mutational, mRNA and protein expression profile of the ras genes
      in 21 glioblastomas multiforme (grade IV), four fibrillary astrocytoma (grade
      II), four anaplastic astrocytoma (grade III) and 15 normal specimens. K-, H- and
      N-ras transcript levels were determined by real-time RT-PCR and mutational status
      by PCR-restriction fragment length polymorphism (RFLP) and direct sequencing. p21
      protein was evaluated by Western blot analysis. Two K-ras mutations were found in
      codons 16 and 26 in one pathological and one normal sample, respectively.
      Glioblastoma multiforme cases exhibited significantly lower K- and H-ras mRNA
      levels compared to controls (P < 10(-4)). K- and H-ras mRNA down-regulation was
      not associated with patient outcome or survival. K-ras was positively correlated
      with H-ras in glioblastomas (P = 0.005), but not in normal specimens. p21 protein
      was absent in all samples. Our findings provide evidence of K- and H-ras
      involvement in brain malignant transformation through transcriptional down
      regulation, while N-ras seems to contribute less to brain carcinogenesis.

PMID- 19179067
TI  - Geographical analysis of thyroid cancer in young people from northern England:
      evidence for a sustained excess in females in Cumbria.
AB  - A previous study found a thyroid cancer excess in Cumbria following the Chernobyl
      explosion, but did not analyse sex-specific effects. This study examines sex
      differences in the incidence of thyroid cancer. Ninety-five primary thyroid
      carcinomas (69 females, 26 males) diagnosed in those aged 0-24 during 1968-2005
      were identified from the Northern Region Young Persons' Malignant Disease
      Registry. Age-standardised incidence rates (ASRs), rate ratios (RRs) and 95%
      confidence intervals (CIs) were calculated. For males, the ASR was 0.6 per
      million person-years during the pre-Chernobyl period (1968-1986), and was 1.8 per
      million person-years during the post-Chernobyl period (1987-2005). For females,
      the ASR was 2.4 pre-Chernobyl and was 3.9 post-Chernobyl. The previously noted
      excess in Cumbria was entirely confined to females (Cumbrian females: RR for post
      Chernobyl compared with pre-Chernobyl=10.8; 95% CI: 1.4-85.3). These findings may
      be consistent with sex-specific differences in susceptibility to an environmental
      exposure, such as fallout from the Chernobyl nuclear accident.

PMID- 19179068
TI  - Address of early stage primary colonic neoplasia by N.O.T.E.S.
AB  - Natural Orifice Translumenal Endoscopic Surgery (N.O.T.E.S.) has the capacity to
      impact greatly on the practice of colorectal surgery. As much as potentially
      providing an alternative means of operative approach, its consideration and
      evolution is already also providing a wealth of instrument innovation that seems
      likely to greatly enhance the endoscopists' armamentarium for advanced
      endoluminal intervention. Furthermore, its aspirational concept is greatly
      advancing the progress of single site incision laparoscopic approaches and is
      speeding appreciation of translumenal assistance and operation. However, if
      N.O.T.E.S. is to occupy a distinct role in the surgical management of colorectal
      disease, it needs a niche indication of its own that constitutes a therapeutic
      advance with considerable clinical benefit for suitable patients. Conversely,
      sound development of a specific stream-lined operative strategy for N.O.T.E.S
      type operations may exert a reciprocal swash upon conventional specialist
      practice. Thus spurred by N.O.T.E.S, localized resection may become standard
      therapy for early stage colonic neoplasia regardless of operative access although
      considerable clinical study is as yet required. Therefore, as much as ensuring
      feasibility and accuracy in the replication of conventional surgical maneuvers,
      the dawn of N.O.T.E.S. should be recognized as an opportunity for the inquisition
      of prevailing surgical principles and prejudices in order that colorectal
      operations are further honed towards perfection (above all it should be realized
      that avoidance of abdominal scarring is not the last barrier before surgical
      nirvana). This may represent the main legacy of transluminal investigation
      whether or not pure N.O.T.E.S. operating ever becomes a clinical reality in its
      own right.

PMID- 19179069
TI  - Reconciling the new demands for food protection with environmental needs in the
      management of livestock wastes.
AB  - Government policy in many countries has been to promote manure management methods
      to reduce the negative impacts related to water and air pollution. The central
      strategy of encouraging manure as a fertiliser rather than treating it as a
      waste, is under threat from new concerns on public health and especially food
      quality. Restrictions on manure applications to certain food crops and the
      stipulation of treatment to 70 degrees C for 1h (in the case of manure products)
      represent barriers to the use of such material as a useful organic product in the
      farming and horticultural industries. However, the sensible development of
      spreading plans in which high and low risk land is identified can enable
      appropriate and effective treatment for each situation and minimise overall cost.
      In the high risk situations, processes based on heat treatment remain the most
      reliable but there still remains the need to ensure a minimum temperature to
      ensure a satisfactory treatment. Direct application of heat available from biogas
      coupled with heat recovery may make thermal treatment of effluents a viable
      option where no effective environmental friendly alternatives exist.

PMID- 19179070
TI  - Aminofurazans as potent inhibitors of AKT kinase.
AB  - AKT inhibitors containing an imidazopyridine aminofurazan scaffold have been
      optimized. We have previously disclosed identification of the AKT inhibitor
      GSK690693, which has been evaluated in clinical trials in cancer patients. Herein
      we describe recent efforts focusing on investigating a distinct region of this
      scaffold that have afforded compounds (30 and 32) with comparable activity
      profiles to that of GSK690693.

PMID- 19179071
TI  - Synthesis of citrate-ciprofloxacin conjugates.
AB  - Two regioisomeric citrate-functionalized ciprofloxacin conjugates have been
      synthesized and their antimicrobial activities against a panel of clinically
      relevant bacteria have been determined. Cellular uptake mechanisms were
      investigated using wild-type and ompF deletion strains of Escherichia coli K-12.

PMID- 19179072
TI  - Small molecules with potent osteogenic-inducing activity in osteoblast cells.
AB  - A chemical screen of 45,000 compounds from a diverse collection led to the
      identification of two series of small molecules with potent osteogenic activity
      in mouse MC3T3-E1 osteoblast cells. The first chemical group was characterized by
      an amino benzothiazole core (AMG0892 series) and the second group by a naphthyl
      amide core (AMG0309 series). Using alkaline phosphatase (ALP), osteocalcin (OCL)
      and calcium as markers of osteoblast differentiation and mineralization, both
      chemical series showed EC(50)s in the 0.01-0.2 microM range and were consistent
      for all three markers. Compounds inhibited cell proliferation, had no effect on
      apoptosis and showed evidence for CREB pathway activity. The present compounds
      represent some of the most potent osteogenic small molecules reported to date and
      provide new tools for elucidating signaling mechanisms in osteoblasts.

PMID- 19179073
TI  - Discovery of N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4
      yl]methyl}benzamides as novel, selective and potent GlyT1 inhibitors.
AB  - Employing an iterative analogue library approach, novel potent and selective
      glycine transporter 1 (GlyT1) inhibitors containing a 4-pyridin-2-ylpiperidine
      sulfonamide have been discovered. These inhibitors are devoid of time-dependent
      CYP inhibition activity and exhibit improved aqueous solubility versus the
      corresponding 4-phenylpiperidine analogues.

PMID- 19179074
TI  - Pseurotin A and its analogues as inhibitors of immunoglobulin E [correction of
      immunoglobuline E] production.
AB  - A natural product, pseurotin A inhibits IgE production in vitro. Wide variety of
      chemical modification of pseurotin A was performed. Structure-activity
      relationship studies of pseurotin analogues elucidated that 10-deoxypseurotin A
      strongly inhibits IgE production with IC(50) of 0.066 microM. An
      immunosuppressive activity of another natural product, synerazol was also found.

PMID- 19179075
TI  - In vitro selection of hemin-binding catalytic RNA.
AB  - Catalytic RNAs with peroxidase activity were obtained by the in vitro selection
      of RNA aptamer-binding hemin. One of the RNA aptamers selected showed binding
      affinity to hemin with a dissociation constant of 0.8muM and exhibited high
      peroxidase activity by forming a complex with hemin. The catalytic efficiency of
      the RNA-hemin complex was 10-fold higher than that of hemin alone.

PMID- 19179076
TI  - Indolyl-pyrrolone as a new scaffold for Pim1 inhibitors.
AB  - Pim1 belongs to a family of serine/threonine kinases, which is involved in the
      control of cell growth, differentiation, and apoptosis. Pim1 plays a pivotal role
      in cytokine signaling and is implicated in the development of a large number of
      tumors, representing a very attractive target for anticancer therapy. In this
      work, we applied a virtual screening protocol aimed at identifying small
      molecules able to inhibit Pim1 activity. The search of novel inhibitors was
      performed through a structure-based molecular modeling approach, taking advantage
      of the availability of the three-dimensional crystal structure of inhibitors
      bound to Pim1. Starting from the knowledge of protein-ligand complexes, the
      software LigandScout was used to generate pharmacophoric models, in turn used as
      queries to perform a virtual screening of databases, followed by docking
      experiments. As a result, a restricted set of candidates for biological testing
      was identified. Finally, among the six compounds selected as potential inhibitors
      of Pim1, two candidates endowed with a significant activity against Pim1 emerged.
      Interestingly, one of these compounds has a chemical scaffold different from
      inhibitors previously identified.

PMID- 19179077
TI  - Synthesis of sulfonyl curcumin mimics exerting a vasodilatation effect on the
      basilar artery of rabbits.
AB  - In order to discover novel small vasodilatory molecules for potential use in the
      treatment of vascular disease, we tested the vasodilatation effect of two types
      of synthetic curcumin mimics, amide type (3) and sulfonyl amide type (4), upon
      the basilar artery of rabbits. In general, the sulfonyl amide type mimic (4) is
      more potent than the amide type (3). Curcumin (1) and compounds 12 and 20
      effectively dilated the basilar artery of white rabbits.

PMID- 19179078
TI  - Four Caucasian patients with mutations in the fukutin gene and variable clinical
      phenotype.
AB  - Fukuyama congenital muscular dystrophy (FCMD) is frequent in Japan, due to a
      founder mutation of the fukutin gene (FKTN). Outside Japan, FKTN mutations have
      only been reported in a few patients with a wide spectrum of phenotypes from
      Walker-Warburg syndrome to limb-girdle muscular dystrophy (LGMD2M). We studied
      four new Caucasian patients from three unrelated families. All showed raised
      serum CK initially isolated in one case and muscular dystrophy.
      Immunohistochemical studies and haplotype analysis led us to search for mutations
      in FKTN. Two patients (two sisters) presented with congenital muscular dystrophy,
      mental retardation, and posterior fossa malformation including cysts, and brain
      atrophy at Brain MRI. The other two patients had normal intelligence and brain
      MRI. Sequencing of the FKTN gene identified three previously described mutations
      and two novel missense mutations. Outside Japan, fukutinopathies are associated
      with a large spectrum of phenotypes from isolated hyperCKaemia to severe CMD,
      showing a clear overlap with that of FKRP.

PMID- 19179079
TI  - Phosphatidylinositol 3-kinase activity is required for the induction of
      differentiation in C6 glioma cells by panaxydol.
AB  - Panaxydol isolated from the lipophilic fractions of Tienchi ginseng (Panax
      notoginseng) induces growth inhibition and differentiation of rat C6 glioma
      cells. The underlying molecular mechanisms are not completely understood. In the
      present study, we identified phosphatidylinositol 3-kinase (PI 3-K) as a
      necessary enzyme for the differentiation of C6 cells treated with panaxydol. The
      specific PI 3-K inhibitor wortmannin resulted in attenuated differentiation of C6
      cells induced by panaxydol, and was associated with perinuclear localization of
      glial fibrillary acidic protein expression and a diminished process formation.
      These data suggest that induction of differentiation in C6 cells by panaxydol
      could be mediated through a PI 3-K-dependent pathway.

PMID- 19179080
TI  - Clinical significance of meniscal abnormalities on magnetic resonance imaging in
      an older population.
AB  - This study examined the prevalence of degenerative changes of knee menisci in
      aging and evaluated the diagnostic values of magnetic resonance (MR) imaging for
      assessing meniscal pathology in an older population. Eighty-five knees of
      asymptomatic volunteers over the age of 40 were scanned using MR imaging.
      Meniscal abnormalities were graded from 0 to 3 according to intrameniscal MR
      signals. The subjects were divided into two groups based on the presence or
      absence of radiographic osteoarthritis. Group I included 43 knees that had normal
      radiographs and group II consisted of 42 knees that had radiographic evidence of
      osteoarthritis. Degenerative changes in the menisci involved primarily the
      posterior segment of the medial meniscus in both groups. Signal changes in the
      other segments were of a significantly lesser grade than that in the posterior
      segment of the medial meniscus. The meniscal grade in each segment was
      significantly higher in group II than in group I. In group I, only two menisci
      (4.6% ) showed grade 3 signals, even in the posterior portion of the medial
      meniscus, compared to 21 (50.0%) in group II. Frequency of asymptomatic grade 3
      was relatively low even in older subjects if there was no evidence of
      radiographic osteoarthritic changes. Abnormal MR signals are more likely to have
      clinical significance, in patients with radiographic changes on plain X-ray.

PMID- 19179081
TI  - Non-peptidic substrate-mimetic inhibitors of Akt as potential anti-cancer agents.
AB  - Akt has emerged as a critical target for the development of anti-cancer
      therapies. It has been found to be amplified, overexpressed, or constitutively
      activated in numerous human malignancies with oncogenesis derived from the
      simultaneous promotion of cell survival and suppression of apoptosis. A valuable
      alternative to the more common ATP-mimetic based chemotherapies is a substrate
      mimetic approach, which has the potential advantage of inherent specificity of
      the substrate-binding pocket. In this paper we present the development of high
      affinity non-peptidic, substrate-mimetic inhibitors based on the minimum GSK3beta
      substrate sequence. Optimization of initial peptidic leads resulted in the
      development of several classes of small molecule inhibitors, which have
      comparable potency to the initial peptidomimetics, while eliminating the
      remaining amino acid residues. We have identified the first non-peptidic
      substrate-mimetic lead inhibitors of Akt 29a-b, which have affinities of 17 and
      12 microM, respectively. This strategy has potential to provide a useful set of
      molecular probes to assist in the validation of Akt as a potential target for
      anti-cancer drug design.

PMID- 19179082
TI  - Design, synthesis, and anti-HIV activity of 4'-modified carbocyclic nucleoside
      phosphonate reverse transcriptase inhibitors.
AB  - A diphosphate of a novel cyclopentyl based nucleoside phosphonate with potent
      inhibition of HIV reverse transcriptase (RT) (20, IC(50)=0.13 microM) has been
      discovered. In cell culture the parent phosphonate diacid 9 demonstrated
      antiviral activity EC(50)=16 microM, within two-fold of GS-9148, a prodrug of
      which is currently under clinical investigation, and within 5-fold of tenofovir
      (PMPA). In vitro cellular metabolism studies using 9 confirmed that the active
      diphosphate metabolite is produced albeit at a lower efficiency relative to GS
      9148.

PMID- 19179083
TI  - Chemistry of polyhalogenated nitrobutadienes, 8: Nitropolychlorobutadienes-
      precursors for insecticidal neonicotinoids.
AB  - Nitropolychlorobutadienes are valuable precursors for highly functionalized
      acyclic or (hetero)cyclic compounds. In this 8th part of our synthetically
      oriented series we focus on the application of these versatile starting materials
      in the synthesis of analogs of the heterocyclic insecticides imidacloprid and
      thiacloprid, and the acyclic counterpart clothianidin. In addition to the main
      synthetic part, leading to imidazolidines or oxazolidines, further promising
      types of compounds derived by subsequent chemical modifications, are introduced.
      Most of the new compounds show high insecticidal activity.

PMID- 19179084
TI  - In vitro studies of cells grown on the superconductor PrO(x)FeAs.
AB  - The recent discovery of arsenic-based high temperature superconductors has
      reignited interest in the study of superconductor: biological interfaces.
      However, the new superconductor materials involve the chemistry of arsenic and
      their toxicity remains unclear [Hand, E., 2008. Nature 452 (24), 922]. In this
      study the possible adverse effects of this new family of superconductors on cells
      have been examined. Cell culture studies in conjunction with microscopy and
      viability assays were employed to examine the influence of arsenic-based
      superconductor PrO(x)FeAs (x=0.75) material in vitro. Imaging data revealed that
      cells were well adhered and spread on the surface of the superconductor.
      Furthermore, cytotoxicity studies showed that cells were unaffected during the
      time-course of the experiments, providing support for the biocompatibility
      aspects of PrO(x)FeAs-based superconductor material.

PMID- 19179085
TI  - Detection of previous neutron irradiation and reprocessing of uranium materials
      for nuclear forensic purposes.
AB  - The paper describes novel analytical methods developed for the detection of
      previous neutron irradiation and reprocessing of illicit nuclear materials, which
      is an important characteristic of nuclear materials of unknown origin in nuclear
      forensics. Alpha spectrometry and inductively coupled plasma sector-field mass
      spectrometry (ICP-SFMS) using solution nebulization and direct, quasi-non
      destructive laser ablation as sample introduction were applied for the
      measurement of trace-level (232)U, (236)U and plutonium isotopes deriving from
      previous neutron irradiation of uranium-containing nuclear materials. The
      measured radionuclides and isotope ratios give important information on the raw
      material used for fuel production and enable confirm the supposed provenance of
      illicit nuclear material.

PMID- 19179086
TI  - Type A and type B monogalactosyldiacylglycerol synthases are spatially and
      functionally separated in the plastids of higher plants.
AB  - Mono- and digalactosyldiacylglycerol (MGDG and DGDG, respectively) constitute the
      bulk of membrane lipids in plant chloroplasts. The final step in MGDG
      biosynthesis occurs in the plastid envelope and is catalyzed by MGDG synthase. In
      Arabidopsis, the three MGDG synthases are classified into type A (atMGD1) and
      type B MGD isoforms (atMGD2 and atMGD3). atMGD1 is an inner envelope membrane
      associated protein of chloroplasts and is responsible for the bulk of
      galactolipid biosynthesis in green tissues. MGD1 function is indispensable for
      thylakoid membrane biogenesis and embryogenesis. By contrast, type B atMGD2 and
      atMGD3 are localized in the outer envelopes and have no important role in
      chloroplast biogenesis or plant development under nutrient-sufficient conditions.
      These type B MGD genes are, however, strongly induced by phosphate (Pi)
      starvation and are essential for alternative galactolipid biosynthesis during Pi
      starvation. MGD1 gene expression is up-regulated by light and cytokinins. By
      contrast, Pi starvation-dependent expression of atMGD2/3 is suppressed by
      cytokinins but induced through auxin signaling pathways. These growth factors may
      control the functional sharing of the inner envelope pathway by atMGD1 and the
      outer envelope pathway by atMGD2/3 according to the growth environment.

PMID- 19179087
TI  - Method selection in craniofacial measurements: advantages and disadvantages of 3D
      digitization method.
AB  - AIM: Treatment of the craniofacial malformations is a primary goal of cranio
      maxillo-facial surgeons. Surgical treatment of these malformations requires
      accurate data. Accuracy of measurement should be a priority of scientists to
      prevent statistical errors and therefore to promote the comparison of the results
      obtained from various research groups. In the present study, we aimed to compare
      three different measurement techniques, which were used frequently in
      craniofacial measurements. METHODS: A total number of 35 female and 35 male
      volunteer adults were included to the study. Two-dimensional (2D) photogrammetry,
      three-dimensional (3D) digitization and manual anthropometry methods were used
      for the present study. Measurements were obtained from the ear, eye, nose and
      face. RESULTS: By comparing three methods, our findings revealed that 3D
      digitization method is an easy, robust, and sensitive method to obtain the data.
      CONCLUSIONS: We think that 3D digitization method is accurate, and it can be
      applied to both clinical practice and research. Advantages and disadvantages of
      three methods are discussed with the relevant literature.

PMID- 19179088
TI  - Bisphosphonate related osteonecrosis of the jaws treated by surgical resection
      and immediate osseous microvascular reconstruction.
AB  - INTRODUCTION: This report presents two patients who received treatment with
      bisphosphonates (BPs) and who subsequently developed BP related osteonecrosis of
      the jaws (BRONJ). The treatment of advanced cases with BRONJ is an area of
      investigation. The possibility of microvascular reconstruction in severe cases of
      BRONJ needs further investigation. MATERIAL AND METHODS: Two patients with
      advanced BRONJ of the left mandible underwent radical resection and immediate
      bony reconstruction with a microvascular osteocutaneous fibula or iliac crest
      flap. Both patients had been treated initially without success using more
      conservative procedures. The progressive course of the disease and refractory
      pain indicated the need to perform radical resection and immediate reconstruction
      of the mandible. RESULTS: Both patients underwent successful resection of the
      affected bone with immediate reconstruction by microvascular flap transfer. After
      reconstruction of the mandible and cover of the defects, both patients recovered
      well with good mandibular function. CONCLUSIONS: Radical resection followed by
      microvascular composite flap reconstruction is reliable in the management of
      patients with advanced BRONJ and can be considered as the fourth therapeutic
      stage.

PMID- 19179089
TI  - When four plus four is less than eight: the Nuss operation.

PMID- 19179091
TI  - Lichens--photophysical studies of potential new sunscreens.
AB  - Fundamental photophysical properties have been obtained for six polyaromatics,
      calycine, usnic acid, vicanicine, 1-Cl-pannerine and epiphorelic acids I and II,
      extracted from Antarctic lichens--potential future sunscreens. None of the lichen
      compounds produced a measurable amount of triplet states and the singlet oxygen
      quantum yield was also very low ranging from 0.003 to 0.06. However, three
      exhibited triplet energy levels which may be above that of thymine. The radical
      cations of calycine and usnic acid were generated via pulse radiolysis and were
      observed to be quenched by vitamin C, vitamin E and Trolox.

PMID- 19179090
TI  - Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular
      NADH concentration and conformation to cell physiology at the single-cell level.
AB  - Reduced nicotinamide adenine dinucleotide, NADH, is a major electron donor in the
      oxidative phosphorylation and glycolytic pathways in cells. As a result, there
      has been recent resurgence in employing intrinsic NADH fluorescence as a natural
      probe for a range of cellular processes that include apoptosis, cancer pathology,
      and enzyme kinetics. Here, we report on two-photon fluorescence lifetime and
      polarization imaging of intrinsic NADH in breast cancer (Hs578T) and normal
      (Hs578Bst) cells for quantitative analysis of the concentration and conformation
      (i.e., free-to-enzyme-bound ratios) of this coenzyme. Two-photon fluorescence
      lifetime imaging of intracellular NADH indicates sensitivity to both cell
      pathology and inhibition of the respiratory chain activities using potassium
      cyanide (KCN). Using a newly developed non-invasive assay, we estimate the
      average NADH concentration in cancer cells (168+/-49 microM) to be approximately
      1.8-fold higher than in breast normal cells (99+/-37 microM). Such analyses
      indicate changes in energy metabolism and redox reactions in normal breast cells
      upon inhibition of the respiratory chain activity using KCN. In addition, time
      resolved associated anisotropy of cellular autofluorescence indicates population
      fractions of free (0.18+/-0.08) and enzyme-bound (0.82+/-0.08) conformations of
      intracellular NADH in normal breast cells. These fractions are statistically
      different from those in breast cancer cells (free: 0.25+/-0.08; bound: 0.75+/
      0.08). Comparative studies on the binding kinetics of NADH with mitochondrial
      malate dehydrogenase and lactate dehydrogenase in solution mimic our findings in
      living cells. These quantitative studies demonstrate the potential of
      intracellular NADH dynamics (rather than intensity) imaging for probing
      mitochondrial anomalies associated with neurodegenerative diseases, cancer,
      diabetes, and aging. Our approach is also applicable to other metabolic and
      signaling pathways in living cells, without the need for cell destruction as in
      conventional biochemical assays.

PMID- 19179092
TI  - Surveillance of patients after initial treatment of ovarian cancer.
AB  - The surveillance of ovarian cancer patients after initial treatment is a
      challenging question in clinical practice. Serum CA 125 assay, physical
      examination, and imaging examinations have been employed with different time
      schedules for the follow-up of asymptomatic patients. Rising serum CA 125 levels
      may precede the clinical detection of relapse in 56-94% of cases with a median
      lead time of 3-5 months. An ongoing randomised phase III European trial is
      comparing the benefits of early administration of chemotherapy based on serum CA
      125 assay alone versus delaying treatment until clinical or radiological
      detection of recurrent disease. Physical examination, with or without ultrasound,
      is very useful for the surveillance of these patients, since approximately 25-50%
      of relapses involve the pelvis. Additional radiological imaging techniques, such
      as computed tomography (CT) and magnetic resonance imaging (MRI), are usually
      performed in asymptomatic patients with rising CA 125 levels as well as in
      patients with suspicious symptoms or signs. Integrated positron emission
      tomography (PET) and CT scanners (PET/CT) can identify recurrent disease in
      tissues that appear normal at CT imaging as well as metastatic lesions intimately
      associated with the bowel wall that are difficult to detect with CT or MRI, so
      that in most series PET/CT has a higher diagnostic reliability than that of
      conventional imaging techniques. Moreover, PET/CT can disclose unusual supra
      diaphragmatic spreading of the disease and may be very helpful for treatment
      planning, especially for the selection of patients suitable for secondary
      surgical cytoreduction. A prospective, randomised trial of therapeutic
      interventions based on stratification by PET/CT disease status could elucidate
      the real impact of this diagnostic procedure in the management of patients with
      recurrent ovarian cancer.

PMID- 19179093
TI  - Hodgkin lymphoma in the elderly: a clinical review of treatment and outcome,
      past, present and future.
AB  - Hodgkin lymphoma (HL) is a curable cancer in the vast majority of patients under
      the age of 60 years. Because of the rarity of the disease in older people, and
      age related factors such as co-morbidity, inability to tolerate aggressive
      chemotherapy, poor ECOG status at presentation and issues relating to frailty,
      the literature is sparse and no prospective randomised studies exist. The
      incidence of HL in the over 60s range between 10% and 20% of the disease overall
      and, as a potentially curable cancer, new specific treatment approaches designed
      for the elderly are necessary. This review discusses the available data in
      relation to treatments and outcome to date, and proposes how future studies and
      evaluations might be constructed for this disease. The SHIELD study (Study of
      Hodgkin lymphoma in the Elderly/Lymphoma Database) is a current example of an
      approach aimed at objectively defining some of the difficulties of this patient
      population.

PMID- 19179094
TI  - Dissemination of intraperitoneal ovarian cancer: Discussion of mechanisms and
      demonstration of lymphatic spreading in ovarian cancer model.
AB  - Ovarian cancer is often accompanied by severe ascites. This complication
      aggravates the disease per se and the chances for its successful treatment. The
      etiology of ascites is not well understood nor are efficient therapies for
      ascites available. These empirical observations support the view that ascites
      might be caused by blocking of lymphatic vessels. Furthermore, it suggests that
      cancer cells might be the blocking agent and could use lymphatic vessels for
      metastatic spreading. To test this hypothesis, we used labeled cancer cells in an
      immuno-competent animal model of ovarian cancer and followed their dissemination.
      These NuTu-19 cells are ovarian cancer cells derived from normal rat ovarian
      epithelial cells, the origin of the most frequent ovarian cancer. Thus studying
      NuTu-19 cell behavior in an animal model is likely to reflect the progression of
      the human disease. To unambiguously document the migration of NuTu-19 cells from
      the peritoneum to remote organs, we generated EGFP expressing NuTu-19 cells by
      transduction with EGFP-lentiviral vectors. The EGFP positive NuTu-19 cells were
      injected intraperitoneally into immuno-competent FISHER 344 rats, and the
      metastatic spreading was monitored. Metastases were observed on the peritoneum,
      the omentum and in the parathymus. This clearly demonstrates that systemic
      spreading of NuTu-19 ovarian cancer cells is conducted by lymphatic ways. Animals
      die 7 weeks after injection, with severe ascites, which suggests that blockage of
      lymphatic drainage by the cancer cell growth is an important complication of the
      disease.

PMID- 19179095
TI  - Poor outcome of elderly patients with platinum-sensitive recurrent ovarian
      cancer: results from the SOCRATES retrospective study.
AB  - BACKGROUND: Elderly patients with ovarian carcinoma have a poorer prognosis
      compared with their younger counterpart, and this depends in most cases on
      undertreatment. The aim of this study was to evaluate, retrospectively, the
      pattern of care and the prognosis of elderly patients with platinum-sensitive
      recurrent ovarian cancer. The SOCRATES study retrospectively assessed the pattern
      of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer
      observed in the years 2000-2002 in 37 Italian centres. Data were collected
      between April and September 2005. PATIENTS AND METHODS: Patients with recurrent
      ovarian cancer with >6 months of platinum free interval were considered eligible.
      Four-hundred-ninety-three patient files were collected and 425 were considered
      eligible and analyzed. Ninety-four patients with age >or=70 years and 331
      patients with age <70 years were analyzed. RESULTS: Recurrence free interval
      (RFI), PS, and number of disease sites were similar among the two groups. A lower
      proportion of elderly patients underwent secondary cytoreduction (8.9% compared
      to 23.9%; p=0.0018). The mean number of chemotherapy lines received for
      recurrence was 2.7 and 2.5 in young and aged patients, respectively. Elderly
      patients received more frequently at second line single agent platinum than
      platinum-combination therapy or other non-platinum chemotherapy. The response
      rate to the second line chemotherapy was higher in younger patients than in the
      elderly population (CR+PR, younger: 67.2%; elderly: 46.5%; p=0.0004). Median
      overall survival from recurrence was 30.7 months in the younger patients and 23.6
      months in the elderly group (p=0.0037). At multivariate analysis, number of
      disease sites (>1 vs. 1), performance status at recurrence (2-3 vs. 0-1), RFI (6
      12 months vs. >12 months), age at recurrence, were independently associated with
      survival. CONCLUSION: Elderly patients with platinum-sensitive recurrent ovarian
      cancer receive less surgery and chemotherapy. Response to chemotherapy is better
      in younger patients. Age is an unfavourable factor independently associated to a
      worst prognosis.

PMID- 19179096
TI  - Deployment performance and retrievability of the Cook Celect vena cava filter.
AB  - PURPOSE: To test the safety, performance, and retrievability of the Cook Celect
      vena cava filter. MATERIALS AND METHODS: Twenty female or castrated male sheep
      were implanted with two Celect filters in series, in the inferior vena cava. The
      animals were divided into five groups of four animals according to day of filter
      retrieval. Filter retrieval occurred at approximately 30, 60, 90, 180, and 360
      days after implantation. At each time point, two sheep underwent retrieval
      attempts of both the cranial and caudal filters. These animals were recovered for
      30 days, at which time healing was assessed. In two additional sheep at each time
      point, retrieval of only the cranial filter was attempted and the caudal filter
      was left in situ. These sheep were euthanized after retrieval, and the segment of
      vena cava encompassing the sites of both the retrieved filter and the filter left
      in situ was excised for gross and histopathologic analysis. RESULTS: Retrieval
      attempts occurred at 34, 62, 90, 188, and 393 days after implantation. All
      retrievals were successful (30 of 30). Tilt was detected in eight filters at
      implantation; six had self-centered before retrieval. At retrieval, no filter
      migration or deformation was reported. All filters were retrieved with acceptable
      levels of force. At each time point, there was evidence of mild intimal
      hyperplasia at the filter anchoring sites and no evidence of vena cava injury.
      CONCLUSIONS: The Celect vena cava filter was safely used as a retrievable filter
      for up to 393 days in an ovine model.

PMID- 19179097
TI  - Sensitive, quantitative carbon-13 NMR spectra by mechanical sample translation.
AB  - Collecting a truly quantitative carbon-13 spectrum is a time-consuming chore.
      Very long relaxation delays, required between transients to allow the z
      magnetization, M(z), of the spin with the longest T(1) to return to the
      equilibrium value, M(0), must precede each transient. These long delays also
      reduce sensitivity, as fewer transients per unit time can be acquired. In
      addition, sometimes T(1) is not known to within even a factor of two: a
      conservative guess for the relaxation delay then leads to very low sensitivity.
      We demonstrate a fresh method to bypass these problems and collect quantitative
      carbon-13 spectra by swapping the sample volume after each acquisition with a
      different portion where the magnetization is already equilibrated to M(0).
      Loading larger sample volumes of 10-20 mL into an unusually long (1520 mm) 5 mm
      OD. NMR tube and vertically sliding the tube between acquisitions accomplishes
      the swap. The relaxation delay can then be skipped altogether. The spectra are
      thus both quantitative, and far more sensitive. We demonstrate the moving tube
      technique on two small molecules (thymol and butylhydroxytoluene) and show good
      carbon-13 quantification. The gain in sensitivity can be as much as 10-fold for
      slowly-relaxing (13)C resonances. These experiments show that quantitative,
      sensitive carbon-13 spectra are possible whenever sufficient sample volumes are
      available. The method is applicable to any slow-relaxing nuclear spin species,
      such as (29)Si, (15)N and other low-gamma nuclei.

PMID- 19179098
TI  - Paraparesis due to interspinous cyst migration into the lumbar canal.

PMID- 19179099
TI  - Screening for celiac disease in patients with osteoporosis.
AB  - OBJECTIVE: Whether patients with osteoporosis should be screened for celiac
      disease is controversial. The objective of this study was to measure the
      prevalence of asymptomatic celiac disease in a cohort of patients with
      osteoporosis. METHODS: We studied 140 patients (133 postmenopausal women and 7
      men) aged 40-75 years (mean age, 62.9+/-9.4 years) with primary osteoporosis
      diagnosed by absorptiometry (spine or hip T-score <-2.5SD). We routinely measured
      serum and urinary calcium, serum phosphate, alkaline phosphatase, 25-OH-vitamin
      D3, and IgG and IgA antigliadin antibodies. Patients with positive antigliadin
      antibody tests were tested for antitransglutaminase antibodies. RESULTS: A
      history of fractures were noted in 52 (37%) patients, with 57 peripheral and 54
      vertebral fractures overall. Vitamin D deficiency was found in 60 (43%) patients.
      IgG antigliadin antibodies were positive in 11 (8%) patients, IgA antigliadin
      antibodies in 11 (8%) patients, and both antibodies in 4 (3%) patients.
      Antitransglutaminase antibodies were negative in all patients. No significant
      differences in laboratory test or absorptiometry results were found between
      patients with versus without IgA antigliadin antibodies. The T-score at the spine
      was nonsignificantly lower in patients with than without IgG antigliadin
      antibodies (-3.17+/-0.49 and -2.82+/-0.77, P=0.076). CONCLUSION: We found no
      excess risk of celiac disease in our cohort of patients with osteoporosis.
      Despite the small sample size, our results cast doubt on the need for celiac
      disease screening in osteoporotic patients who have no gastrointestinal symptoms.

PMID- 19179100
TI  - Individual- and community-level determinants of social acceptance of people
      living with HIV in Kenya: results from a national population-based survey.
AB  - Using the 2003 Kenya Demographic and Health Survey, we investigated the influence
      of individual- and community-level factors on accepting attitudes toward people
      living with HIV (PLHIV) using three outcomes: (1) willingness to care for an
      infected household member, (2) willingness to buy vegetables from an infected
      vendor, and (3) willingness to allow an infected female teacher to continue
      teaching. In multilevel logistic regression models, we found that individuals who
      expressed greater acceptance of PLHIV were more likely to be male, older, more
      educated, high AIDS knowledge, and exposed to mass media. At the community level,
      differences in accepting attitudes were associated with community AIDS knowledge,
      community education, and community AIDS experience, but not for region, or place
      of residence. The findings suggest the important role of community factors in
      determining social acceptance of PLHIV. Programmatic strategies aimed at
      increasing these accepting attitudes should consider both individual- and
      community-level factors.

PMID- 19179101
TI  - Altered lumbopelvic movement control but not generalized joint hypermobility is
      associated with increased injury in dancers. A prospective study.
AB  - Dancers experience significant more low back pain (LBP) than non-dancers and are
      at increased risk of developing musculoskeletal injuries. Literature concerning
      the relationship between joint hypermobility and injury in dancers remains
      controversial. The purpose of this study was therefore to examine whether
      lumbopelvic movement control and/or generalized joint hypermobility would predict
      injuries in dancers. Four clinical tests examining the control of lumbopelvic
      movement during active hip movements were used in combination with joint
      hypermobility assessment in 32 dancers. Occurrence of musculoskeletal injuries,
      requiring time away from dancing, was recorded during a 6-month prospective
      study. Logistic regression analysis was used to predict the probability of
      developing lower limb and/or lumbar spine injuries. Twenty-six injuries were
      registered in 32 dancers. Forty-four percent of the dancers were hypermobile. A
      logistic regression model using two movement control tests, correctly allocated
      78% of the dancers. The results suggest that the outcome of two lumbopelvic
      movement control tests is associated with an increased risk of developing lower
      extremities or lumbar spine injuries in dancers. Neither generalized joint
      hypermobility, evaluated with the Beighton score, nor a history of LBP was
      predictive of injuries. Further study of these interactions is required.

PMID- 19179102
TI  - Towards a systems-based understanding of plant desiccation tolerance.
AB  - Vegetative desiccation tolerance occurs in a unique group of species termed
      'resurrection plants'. Here, we review the molecular genetic, physiological,
      biochemical, ultrastructural and biophysical studies that have been performed on
      a variety of resurrection plants to discover the mechanisms responsible for their
      tolerance. Desiccation tolerance in resurrection plants involves a combination of
      molecular genetic mechanisms, metabolic and antioxidant systems as well as
      macromolecular and structural stabilizing processes. We propose that a systems
      biology approach coupled with multivariate data analysis is best suited to
      unraveling the mechanisms responsible for plant desiccation tolerance, as well as
      their integration with one another. This is of particular relevance to molecular
      biological engineering strategies for improving plant drought tolerance in
      important crop species, such as maize (Zea mays) and grapevine (Vitis vinifera).

PMID- 19179104
TI  - Epigenetic regulation of stress responses in plants.
AB  - Gene expression driven by developmental and stress cues often depends on
      nucleosome histone post-translational modifications and sometimes on DNA
      methylation. A number of studies have shown that these DNA and histone
      modifications play a key role in gene expression and plant development under
      stress. Most of these stress-induced modifications are reset to the basal level
      once the stress is relieved, while some of the modifications may be stable, that
      is, may be carried forward as 'stress memory' and may be inherited across mitotic
      or even meiotic cell divisions. Epigenetic stress memory may help plants more
      effectively cope with subsequent stresses. Comparative studies on stress
      responsive epigenomes and transcriptomes will enhance our understanding of stress
      adaptation of plants.

PMID- 19179105
TI  - A new HCV genotype 6 subtype designated 6v was confirmed with three complete
      genome sequences.
AB  - BACKGROUND: Although hepatitis C virus (HCV) genotype 6 is classified into 21
      subtypes, 6a-6u, new variants continue to be identified. OBJECTIVE: To
      characterize the full-length genomes of three novel HCV genotype 6 variants:
      KMN02, KM046 and KM181. STUDY DESIGN: From sera of patients with HCV infection,
      the entire HCV genome was amplified by RT-PCR followed by direct DNA sequencing
      and phylogenetic analysis. RESULTS: The sera contained HCV genomes of 9461, 9429,
      and 9461nt in length, and each harboured a single ORF of 9051nt. The genomes
      showed 95.3-98.1% nucleotide similarity to each other and 72.2-75.4% similarity
      to 23 genotype 6 reference sequences, which represent subtypes 6a-6u and
      unassigned variants km41 and gz52557. Phylogenetic analyses demonstrated that
      they were genotype 6, but were subtypically distinct. Based on the current
      criteria of HCV classification, they were designed to represent a new subtype,
      6v. Analysis of E1 and NS5B region partial sequences revealed two additional
      related variants, CMBD-14 and CMBD-86 that had been previously reported in
      northern Thailand and sequences dropped into Genbank. CONCLUSION: Three novel HCV
      genotype 6 variants were entirely sequenced and designated subtype 6v.

PMID- 19179103
TI  - New developments in Hsp90 inhibitors as anti-cancer therapeutics: mechanisms,
      clinical perspective and more potential.
AB  - The molecular chaperone Hsp90 (heat shock protein 90) is a promising target in
      cancer therapy. Preclinical and clinical evaluations of a variety of Hsp90
      inhibitors have shown anti-tumor effect as a single agent and in combination with
      chemotherapy. Current Hsp90 inhibitors are categorized into several classes based
      on distinct modes of inhibition, including (i) blockade of ATP binding, (ii)
      disruption of co-chaperone/Hsp90 interactions, (iii) antagonism of client/Hsp90
      associations and (iv) interference with post-translational modifications of
      Hsp90. The different functions of Hsp90 isoforms and the isoform selectivity of
      drugs need further investigation. The correlation of cell surface Hsp90 with
      cancer metastasis and the emerging involvement of Hsp90 inhibition in cancer stem
      cells have become exciting areas that could be exploited. Therefore, the aim of
      this review is (1) to summarize the up-to-date knowledge of mechanistic studies
      and clinical prospect of currently available Hsp90 inhibitors, (2) to enhance our
      perspectives for designing and discovering novel Hsp90 inhibitors, and (3) to
      provide an insight into less-understood potential of Hsp90 inhibition in cancer
      therapy.

PMID- 19179106
TI  - An outbreak of hepatitis A associated with the consumption of raw beef.
AB  - BACKGROUND: In July 2004, a sharp increase of hepatitis A, a notifiable disease
      in Belgium, was detected. OBJECTIVES: We investigated the outbreak in order to
      identify the source and take appropriate action. STUDY DESIGN: We conducted an
      outbreak investigation which included a matched case-control study to analyse the
      association with a range of food items and food providers. A phylogenetic
      analysis was used to study the relation between the outbreak cases and the
      identified source. RESULTS: We registered 269 cases of hepatitis A. Consumption
      of raw beef (OR 16.0; 95% CI 2.1-120.7) was the most probable way of infection. A
      food handler working at an epidemiologically linked meat distribution plant had
      contracted hepatitis A 1 month before the start of the outbreak. HAV strains from
      the food handler and the patients involved in the outbreak were monophyletically
      related. CONCLUSIONS: Since serological immunity in Belgium is decreasing over
      time, foodborne outbreaks of hepatitis A are a substantial risk. In this
      outbreak, a single food handler, at the level of the distribution chain, has been
      identified as the most likely source, through cross-contamination of raw beef.
      This outbreak investigation suggests the need to consider vaccination against
      hepatitis A in food handlers.

PMID- 19179107
TI  - Diagnosing rotavirus A associated IID: Using ELISA to identify a cut-off for real
      time RT-PCR.
AB  - BACKGROUND: The use of RT-PCR for diagnosis of group A rotaviruses is increasing,
      but up to 14% of healthy individuals may be positive by RT-PCR. If RT-PCR is not
      well correlated with disease, rotavirus A may not always be the cause of illness
      in RT-PCR positive patients with infectious intestinal disease (IID). OBJECTIVES:
      To describe the differences in faecal viral load between ELISA positive IID
      cases, RT-PCR positive cases and healthy controls. To develop a cut-off in faecal
      viral load for attributing illness to rotavirus A in RT-PCR positive IID cases.
      STUDY DESIGN: Faecal viral load was measured, using real time RT-PCR, in 118
      community IID cases and 65 healthy controls, previously tested by ELISA. Cycle
      threshold (Ct) values from the real-time RT-PCR were used as a proxy measure of
      viral load. A cut-off for attributing illness to rotavirus A was selected, using
      ROC analysis. RESULTS: There was little overlap in viral load between ELISA
      positive IID cases (median Ct 17) and healthy controls (median Ct 37), but ELISA
      negative, RT-PCR positive IID cases (median Ct 37) had viral loads similar to
      healthy controls, indicating that RT-PCR is not detecting extra cases of group A
      rotavirus associated IID, only sub-clinical infections. The optimal cut-off in
      the real time RT-PCR was at Ct value 24-27. CONCLUSION: ELISA is the best method
      for the laboratory diagnosis of rotavirus A associated IID. If RT-PCR is used, it
      is advisable to use a real time platform and to use a viral load cut-off
      equivalent to the detection limit of ELISA.

PMID- 19179108
TI  - Human astrovirus infection in children with gastroenteritis in Shanghai.

PMID- 19179109
TI  - Utility of newborn screening cards for detecting CMV infection in cases of
      stillbirth.
AB  - BACKGROUND: CMV infection may cause intrauterine deaths including stillbirths
      (intrauterine deaths at > or =20 weeks gestation). In 2005, there were 1979
      stillbirths in Australia, which is almost double the number of deaths reported
      for all children between 1 and 14 years age. OBJECTIVES: We evaluated the
      diagnostic utility of testing for the presence of CMV in newborn blood screening
      cards (NBSC) collected from stillborn babies, who had no known cause of death
      after post-mortem. STUDY DESIGN: Blood taken at post-mortem by cardiac puncture
      of 107 stillborn babies between July 2005 and December 2006, was spotted onto
      NBSC. CMV infection was detected using nested PCR targeting the glycoprotein
      gene, gp58. RESULTS: Of the 107 stillborn infants, 10 (9%) were CMV positive. The
      rate of CMV infection did not differ between early stillbirths (8%) and late
      stillbirths (9%). CONCLUSIONS: The use of NBSC is a convenient and accurate
      method for CMV detection in stillbirths. It is easily collected, less laborious
      than viral culture, diagnostically useful and could be applied for
      epidemiological and retrospective investigation of the virus in the stillbirth
      population.

PMID- 19179110
TI  - Sleep perception in insomniacs, sleep-disordered breathing patients, and healthy
      volunteers--an important biologic parameter of sleep.
AB  - BACKGROUND: The mechanisms involved in sleep perception are not widely known.
      Therefore, we believe that investigating this phenomenon is the best way to
      understand some of the mechanisms involved in several sleep disturbances,
      particularly insomnias. OBJECTIVE: The objective of our study was to evaluate
      sleep perception in insomniacs, sleep-disordered breathing (SDB) patients, and
      healthy volunteers. Our hypothesis was that insomniacs have less sleep perception
      than healthy individuals and patients with sleep respiratory disorders. METHODS:
      We studied 199 individuals who were divided into the following four groups: (1)
      insomnia group; (2) patients with sleep-disordered breathing; (3) patients with
      insomnia complaints and an associated sleep respiratory disorder; and (4) healthy
      individuals with no sleep complaints. All patients were subjected to
      polysomnography (PSG) followed by a questionnaire addressing their perception
      about the previous night's sleep. In addition to analysis of all sleep
      parameters, we determined sleep perception as the percentage of the ratio between
      total sleep time perceived by the patient and the total sleep time obtained by
      PSG. RESULTS: Sleep perception was significantly lower in insomnia patients than
      in sleep-disordered breathing patients or the normal group. In addition, no
      significant differences across the four groups were observed in sleep efficiency
      and total sleep time. CONCLUSIONS: The results showed that the reported sleep
      perception of insomniacs is lower than that of sleep-disordered breathing
      patients or normal individuals. We believe that sleep perception is as important
      as other commonly measured parameters, such as sleep efficiency.

PMID- 19179111
TI  - CPAP treatment in obstructive sleep apnoea: a randomised, controlled trial of
      follow-up with a focus on patient satisfaction.
AB  - AIM OF THE STUDY: To assess a simplified model for follow-up in patients
      undergoing CPAP-treatment for obstructive sleep apnoea syndrome. PATIENTS AND
      METHODS: A total of 200 patients in stable condition were randomised to annual
      follow-up visits either by a specialist nurse (intervention) or physician-led
      visits including oximetry (control). Patients were followed for two years and
      assessed for the following outcomes: global satisfaction, quality of life,
      medical events, and resource utilisation. RESULTS: The overall experience of CPAP
      treatment was rated as excellent or good by 99% in each group. Global
      satisfaction was high in both groups, and there were no clinically significant
      differences between the groups. Quality of life did not differ between the
      groups. No serious medical events related to OSAS occurred during the study
      period. Extra physician consultations occurred rarely, and were managed within
      the limits of the follow-up visits. CONCLUSION: For stable patients undergoing
      CPAP treatment for obstructive sleep apnoea, regular follow-up visits by a
      specialist nurse can optimise the use of health care resources while retaining
      high patient satisfaction, without increasing medical risks.

PMID- 19179112
TI  - Summary of the second meeting of the International Forum on Water Hygiene in
      Buildings (IFOWAHB) from 01 to 02.06.2007 in Stockholm.

PMID- 19179113
TI  - Family members' perceptions of genetic testing for malignant melanoma--a
      prospective interview study.
AB  - PURPOSE: The aim was to prospectively explore experiences related to genetic
      testing for malignant melanoma among unaffected previously untested members of
      melanoma-prone families in which germline CDKN2A mutations had been identified.
      METHOD: Consecutive members of families with CDKN2A mutation attending a
      pigmented lesion clinic (n=11) were interviewed and completed questionnaires at
      four occasions: before genetic testing, at disclosure of genetic test result and
      six months and one year after disclosure. The following areas were measured:
      anxiety and depression, risk perception, and sun-related habits. RESULTS:
      Disclosure of the test result did not seem to change family members' perception
      of their risk of developing melanoma. Few members reported anxiety of clinical
      significance and no one were depressed. All family members with biological
      children expressed concerns regarding their children and emphasized the
      importance of sun protection and surveillance. Sun burns and blisters were rather
      commonly reported by the family members. Routines regarding the procedure for
      conveying test result were requested. CONCLUSION: Genetic testing of the members
      of melanoma families with CDKN2A mutations attending a pigmented lesion clinic
      did not appear to induce behavioral changes related to sun habits or emotional
      problems. Concerns about the future of their children were commonly expressed by
      participants.

PMID- 19179115
TI  - Anterior scoliosis rod migration to the lower extremity.
AB  - BACKGROUND CONTEXT: Scoliosis rod migration has been reported rarely in the
      literature. We present a case study on three patients with distant migration of
      anterior scoliosis rod implants. PURPOSE: To report an unusual complication of
      rod migration of anterior retroperitoneally implanted scoliosis rods in three
      patients. STUDY DESIGN/SETTING: A retrospective case report. METHODS:
      Radiographic analysis. RESULTS: Asymptomatic rod migration occurred from the
      anterior spine to the lower extremity in two cases and to the retroperitoneal
      space in the third case. The rod fragment appeared in the lower extremity in two
      cases and was removed through a small skin incision in the extremity. The average
      time from scoliosis surgery until the rods were found at a distant site was 9
      years. CONCLUSIONS: The scoliosis surgery was effective in preventing further
      deformity; however, in two cases there was nonunion at one or two levels.
      Patients are asymptomatic at the present time and followed at regular intervals
      to see if further surgery is necessary to correct areas of nonunion.

PMID- 19179116
TI  - Course of the vertebral artery in C2.

PMID- 19179114
TI  - Hyperglycemia during acute coronary syndrome: a nurse-managed insulin infusion
      protocol for stricter and safer control.
AB  - BACKGROUND: Diabetic patients with acute coronary syndromes (ACS) might benefit
      from tight glycemic control by means of insulin infusion. Nurse-implemented
      insulin infusion protocols (IIP) are available but none validated in patients
      with ACS admitted to a coronary care unit (CCU). AIMS: To assess feasibility,
      effectiveness and safety of a new nurse-managed IIP (Desio Diabetes Diagram, DDD)
      for intensive glucose control in patients with suspected ACS and known diabetes
      or blood glucose (BG) >200 mg/dL. METHODS AND RESULTS: To reach and maintain a
      target BG level of 100-139 mg/dL we adopted a nomogram based on the percent
      changes in the insulin infusion rate according to the current BG value and the
      percent change from previous BG level. Ninety-one consecutive patients (53 men,
      mean age 69.7+/-11.2 years) were treated with DDD IIP. Baseline BG was 202.2+/
      86.8 mg/dL. The median time to achieve the target was 3 h (Q1-Q3 2-5 h).
      Afterwards target BG levels were maintained for 70.4+/-15.9% of the time. During
      5004 h of insulin infusion BG never fell below 40 mg/dL. CONCLUSIONS: The nurse
      managed DDD IIP was easily implemented in our CCU and permitted strict and safe
      glycemic control in hyperglycemic patients with ACS.

PMID- 19179117
TI  - Central bombesin activates adrenal adrenaline- and noradrenaline-containing cells
      via brain thromboxane A2 in rats.
AB  - The sympathetic nervous system regulates peripheral organs via the adrenal
      chromaffin cells containing adrenaline (A-cells) or noradrenaline (NA-cells) and
      the sympathetic ganglia. We examined the effect of intracerebroventricularly
      administered bombesin on neuronal activities of adrenal A-cells and NA-cells and
      several kinds of sympathetic ganglia (superior cervical, stellate and celiac
      ganglia) using c-Fos (a marker for neuronal activation), with regard to brain
      prostanoid, in anesthetized rats. Bombesin induced c-Fos in both adrenal A-cells
      and NA-cells, but not in any of the sympathetic ganglia. Central pretreatment
      with either indomethacin (a cyclooxygenase inhibitor) or furegrelate (a
      thromboxane A(2) synthase inhibitor) abolished all bombesin-induced responses.
      These results suggest that bombesin centrally activates adrenal A-cells and NA
      cells by brain thromboxane A(2)-mediated mechanisms in rats.

PMID- 19179118
TI  - Cardiovascular and baroreceptor functions of the paratrigeminal nucleus for
      pressor effects in non-anaesthetized rats.
AB  - Located in the lower brainstem, the paratrigeminal nucleus (Pa5) is related to
      cardiorespiratory autonomic reflex functions. To characterize the structures'
      role in blood pressure regulation and baroreflex response, both resting
      cardiovascular parameters and reflex responses were evaluated during
      phenylephrine-produced pressor responses in non-anaesthetized rats with or
      without bilateral chemical Pa5 ablation. The Pa5-ablated animals, in contrast to
      the Pa5-intact control animals, presented increased resting arterial pressure
      (115+/-4 vs. 100+/-3 mm Hg), decreased heart (293+/-10 vs. 315+/-7 bpm) and
      increase of the respiratory (104+/-3 vs. 94+/-5 rpm) rates, larger pressor
      responses and reduced baroreflex index (1.6+/-0.2 vs. 2.8+/-0.2, p<0.05). The
      cardiovascular changes, compatible to those produced by nucleus of the solitary
      tract (NTS) lesions in non-anaesthetized rats, indicate a reduction of both the
      sympathetic and cardiac components of the baroreflex response. Further analyses
      showed the Pa5 mediates reflex responses to smaller blood pressure increases,
      while the NTS would be predominantly active in surges over 40 mm Hg. Thus, the
      integrity of the Pa5 is important for resting blood pressure maintenance as for a
      full baroreceptor response.

PMID- 19179119
TI  - A case of sick sinus syndrome and autonomic failure with Parkinson's disease.

PMID- 19179120
TI  - Characterization in vitro and in vivo of the DNA helicase encoded by Deinococcus
      radiodurans locus DR1572.
AB  - Deinococcus radiodurans survives extremely high doses of ionizing and ultraviolet
      radiation and treatment with various DNA-damaging chemicals. As an effort to
      identify and characterize proteins that function in DNA repair in this organism,
      we have studied the protein encoded by locus DR1572. This gene is predicted to
      encode a Superfamily I DNA helicase, except that genome sequencing indicated that
      it has a one-base frameshift and would not encode a complete helicase. We have
      cloned the gene from two different D. radiodurans strains and find that the
      frameshift mutation is not present. The corrected gene encodes a 755 residue
      protein that is similar to the Bacillus subtilis YvgS protein and to helicase IV
      of Escherichia coli. The purified protein (helicase IV(Dr)) has ATP hydrolysis
      and DNA helicase activity. A truncated protein that lacks 214 residues from the N
      terminus, which precede the conserved helicase domain, has greater ATPase
      activity than the full-length protein but has no detectable helicase activity.
      Disruption of locus DR1572 in the D. radiodurans chromosome causes greater
      sensitivity to hydrogen peroxide and methyl-methanesulfonate compared to wild
      type cells, but no change in resistance to gamma and ultraviolet radiation and to
      mitomycin C. The results indicate that locus DR1572 encodes a complete protein
      that contributes to DNA metabolism in D. radiodurans.

PMID- 19179121
TI  - Involvement of specialized DNA polymerases in mutagenesis by 8-hydroxy-dGTP in
      human cells.
AB  - The mutagenicity of an oxidized form of dGTP, 8-hydroxy-2'-deoxyguanosine 5'
      triphosphate (8-OH-dGTP), was examined using human 293T cells. Shuttle plasmid
      DNA containing the supF gene was first transfected into the cells, and then 8-OH
      dGTP was introduced by means of osmotic pressure. The DNAs replicated in the
      cells were recovered and then transfected into Escherichia coli. 8-OH-dGTP
      induced A:T-->C:G substitution mutations in the cells. The knock-downs of DNA
      polymerases eta and zeta, and REV1 by siRNAs reduced the A:T-->C:G substitution
      mutations, suggesting that these DNA polymerases are involved in the
      misincorporation of 8-OH-dGTP opposite A in human cells. In contrast, the knock
      down of DNA polymerase iota did not affect the 8-OH-dGTP-induced mutations. The
      decrease in the induced mutation frequency was more evident by double knock-downs
      of DNA pols eta plus zeta and REV1 plus DNA pol zeta (but not by that of DNA pol
      eta plus REV1), suggesting that REV1-DNA pol eta and DNA pol zeta work in
      different steps. These results indicate that specialized DNA polymerases are
      involved in the mutagenesis induced by the oxidized dGTP.

PMID- 19179122
TI  - Nutritional decline in cystic fibrosis related diabetes: the effect of intensive
      nutritional intervention.
AB  - BACKGROUND: Reports indicate that nutritional and respiratory decline occur up to
      four years prior to diagnosis of cystic fibrosis related diabetes (CFRD). Our aim
      was to establish whether intensive nutritional intervention prevents pre-diabetic
      nutritional decline in an adult population with CFRD. METHODS: 48 adult patients
      with CFRD were matched to 48 controls with CF, for age, gender and lung pathogen
      status. Nutritional and other clinical indices were recorded at annual intervals
      from six years before until two years after diagnosis. Data were also analysed to
      examine the impact of early and late acquisition of CFRD. RESULTS: No important
      differences in weight, height, body mass index (BMI), lung function or
      intravenous treatment were found between groups in the six years prior to
      diagnosis, nor any significant deviation over time. In those who developed
      diabetes, use of overnight enteral tube feeding (ETF) was four times as likely at
      the time of diagnosis, compared to controls [ETF 43.8% (CFRD) v 18.8% (CF
      Controls), OR 4.0, CI 1.3 to 16.4, p=0.01]. Age at onset of CFRD played a
      significant role in determining the pre-diabetic clinical course. Younger
      diabetics with continued growth at study onset (n=17) had a lower BMI from 2
      years prior to diagnosis compared to controls [BMI 18.9 kg/m(2) (CFRD) v 20.8
      kg/m(2) (CF Controls), diff=1.9, CI -0.1 to 3.7 p=0.04]. The BMI of older
      diabetics (completed growth at study onset) was equal to that of controls
      throughout. CONCLUSION: Pre-diabetic nutritional decline is not inevitable in
      adults with CFRD, but is influenced by age of onset. In the group overall, those
      with CFRD are more likely to require ETF from 2 years prior to diagnosis. Despite
      intensive nutritional intervention, patients who continue to grow throughout the
      pre-diabetic years, show a level of nutritional decline absent in older adults.

PMID- 19179123
TI  - Confirmatory analysis of firocoxib in bovine milk by rapid resolution liquid
      chromatography tandem mass spectrometry.
AB  - A rapid method has been developed to analyse for firocoxib (FIRO) residue in
      bovine milk. Milk samples were extracted with acetonitrile and sample extracts
      were purified on Evolute ABN solid phase extraction cartridges. Aliquots were
      analysed by rapid resolution liquid chromatography tandem mass spectrometry (RRLC
      MS/MS). The method was validated in bovine milk, according to the criteria
      defined in Commission Decision 2002/657/EC. The decision limit (CCalpha) was
      1.18ng/mL and for the detection capability a (CCbeta) value of 2.02ng/mL was
      obtained. The measurement uncertainty of the method was 27%. Fortifying bovine
      milk samples (n=18) in three separate assays, show the accuracy of the method to
      be between 96 and 105%. The precision of the method, expressed as RSD values for
      the within-lab reproducibility at the three levels of fortification (5, 7.5 and
      10ng/mL) was less than 11% respectively.

PMID- 19179124
TI  - Development and validation of an LC-MS/MS method for quantification of cyclic
      guanosine 3',5'-monophosphate (cGMP) in clinical applications: a comparison with
      a EIA method.
AB  - An LC-MS/MS method was developed and validated to quantify endogenous cyclic
      guanosine 3',5'-monophosphate (cGMP) in human plasma. The LC-MS/MS and
      competitive enzyme immunoassay (EIA) assays were compared. cGMP concentrations of
      20 human plasma samples were measured by both methods. For the MS-based assay,
      plasma samples were subjected to a simple protein precipitation procedure by
      acetonitrile prior to analysis by electrospray ionization LC-MS/MS. De-protonated
      analytes generated in negative ionization mode were monitored through multiple
      reaction monitoring (MRM). A stable isotope-labeled internal standard,
      (13)C(10),(15)N(5)-cGMP, which was biosynthesized in-house, was used in the LC
      MS/MS method. The competitive EIA was validated using a commercially available
      cGMP fluorescence assay kit. The intra-assay accuracy and precision for MS-based
      assay for cGMP were 6-10.1% CV and -3.6% to 7.3% relative error (RE),
      respectively, while inter-assay precision and accuracy were 5.6-8.1% CV and -2.1%
      to 6.3% RE, respectively. The intra-assay accuracy and precision for EIA were
      17.9-27.1% CV and -4.9% to 24.5% RE, respectively, while inter-assay precision
      and accuracy were 15.1-39.5% CV and -30.8% to 4.37% RE, respectively. Near the
      lower limits of detection, there was little correlation between the cGMP
      concentration values in human plasma generated by these two methods (R(2)=0.197,
      P=0.05). Overall, the MS-based assay offered better selectivity, recovery,
      precision and accuracy over a linear range of 0.5-20ng/mL. The LC-MS/MS method
      provides an effective tool for the quantitation of cGMP to support clinical
      mechanistic studies of curative pharmaceuticals.

PMID- 19179125
TI  - Validation of bioanalytical LC-MS/MS assays: evaluation of matrix effects.
AB  - Liquid chromatography coupled to atmospheric pressure ionization tandem mass
      spectrometry is currently the method of choice for the quantitative determination
      of drugs in biological matrices. The advantages of this technique include high
      specificity, sensitivity and throughput. However, co-eluting matrix components,
      which are not observed in the chromatogram, can have a detrimental effect on the
      analysis, since they can cause ion suppression or enhancement of the analyte. The
      evaluation of matrix effects on the quantitative analysis of drugs in biological
      fluids is an important and sometimes overlooked aspect of assay validation. In
      this review, the influence of matrix effects on bioanalytical LC-MS/MS methods is
      discussed and illustrated with some examples. In addition, possible solutions to
      reduce or eliminate matrix effects are highlighted. A literature overview of
      validated LC-MS/MS methods published from January till June 2008 is also
      included. Although matrix effects are investigated in most papers, there is no
      consensus on how matrix effects should be evaluated during method validation. In
      addition, the definition of specificity should be changed for LC-MS/MS based
      methods.

PMID- 19179126
TI  - Use of the total error approach to evaluate the performance of a semi
      quantitative immunological method (BIACORE method) for detecting sulfamethazine
      in bovine milk.
AB  - A semi-quantitative immunological method (BIACORE method) for detecting
      sulfamethazine in bovine milk was developed and validated using the total error
      approach. The acceptance limits were set at +/-40% and the risk of procedure of
      (1-beta) proportion measurements falling outside the acceptance limits was chosen
      at 5%. Different response functions were tested on the basis of the accuracy
      index (I(A)). The best model was a weighted (1/X(2)) quadratic regression and the
      simplest one was an unweighted quadratic regression. This approach identified the
      weak point of the method, which was precision. Finally this BIACORE method was
      able to detect positive samples containing sulfamethazine in the dosing range
      between 50 and 150 ng/ml.

PMID- 19179128
TI  - Creep-resistant elastomeric networks prepared by photocrosslinking fumaric acid
      monoethyl ester-functionalized poly(trimethylene carbonate) oligomers.
AB  - Biodegradable elastomeric networks were prepared from ethyl fumarate
      functionalized poly(trimethylene carbonate) oligomers. Photocrosslinkable
      macromers were synthesized by reacting three-armed, hydroxyl group-terminated
      poly(trimethylene carbonate) oligomers with fumaric acid monoethyl ester at room
      temperature using N,N-dicyclohexylcarbodiimide as a coupling agent and 4
      dimethylamino pyridine as a catalyst. Poly(trimethylene carbonate) macromers with
      molecular weights ranging between 4500 and 13,900 were prepared and crosslinked
      by ultraviolet-initiated radical polymerization. The gel contents of the
      resulting transparent networks varied between 74% and 80%. All obtained networks
      had low glass transition temperatures, which varied between -18 and -13 degrees
      C. They showed rubber-like behavior and excellent mechanical properties, with
      tensile strengths and elongations at break of up to 17.5 MPa and 750%,
      respectively. Moreover, static- and dynamic creep experiments showed that these
      amorphous networks were highly elastic and resistant to creep. In cyclic tensile
      testing to 50% strain, the permanent deformation after 20 cycles was 0%, while
      static creep tests at 35% of the yield stress did not indicate creep or permanent
      deformation after removal of the load. Porous structures were prepared by
      photopolymerizing the macromers in the presence of salt particles, and subsequent
      leaching of the salt. Such networks, built up of non-toxic compounds and designed
      to release benign degradation products, may find application as tissue
      engineering scaffolds for dynamic cell culture.

PMID- 19179127
TI  - High efficacy of bismuth subcitrate for Helicobacter pylori eradication in
      pangastritis.
AB  - BACKGROUND: The influence of gastritis patterns in Helicobacter pylori
      eradication rates has been poorly investigated. AIMS: To compare the efficacy of
      bismuth or proton pump inhibitors triple therapy for H. pylori eradication in
      pangastritis. PATIENTS AND METHODS: One hundred and eight patients with
      pangastritis were assigned to either lansoprazole 30 mg once a day (n=54) or
      bismuth 240 mg bis in die (n=54) for 14 days combined, for the first week, with
      amoxicillin 1g plus metronidazole 250 mg tris in die. Eradication was confirmed
      by (13)C-urea breath test. RESULTS: With bismuth, successful eradication was
      observed in 75.9% (41/54) in the intention-to-treat analysis and 78.8% (41/52) in
      the per-protocol analysis. With lansoprazole, the eradication rates were
      respectively 46.3% (25/54) and 51.0% (25/49). Bismuth had a significant higher
      efficacy according to both intention-to-treat analysis (p=0.0029) and per
      protocol analysis (p=0.0038) with OR of 3.66 (95% CI: 1.61-8.32) and 3.58 (95%
      CI: 1.50-8.54) respectively. At regression analysis, the only independent
      variable affecting eradication was the type of regimen (p=0.026) with an OR of
      3.31 (95% CI: 1.16-9.44). CONCLUSIONS: In pangastritis patients, bismuth is more
      effective than PPI in first-line eradication. For improving the overall
      eradication rates, an evaluation of gastritis extent might need to be considered.

PMID- 19179129
TI  - Pregnancy and protection: perceptions, attitudes and experiences of Australian
      female adolescents.
AB  - BACKGROUND AND PURPOSE: Despite decades of research, development and evaluation
      of educational and promotional strategies to prevent teenage pregnancy, we have
      only a limited understanding of the strategies that are effective and why. This
      study sought to explore female teenagers' attitudes, perceptions and experiences
      of contraceptive use, and describe the influence of this on pregnancy risk.
      METHODS: A qualitative approach was used to explore the contraceptive behaviour
      in a purposive sample of sexually active Australian females aged 14-19 years.
      Teenagers were drawn from three sub-groups: antenatal and postnatal services
      (pregnant-continuing); termination services (pregnant-terminating); and sexual
      health clinics (never-pregnant). Sixty-eight individual, semi-structured
      interviews were conducted. Thematic analysis was employed to analyse the data and
      generate a rich, description of contraceptive behaviour. RESULTS: Whilst
      participants were familiar with contraception, many used it inconsistently.
      Commitment to pregnancy prevention was firmly located within participants'
      attitudes toward teenage pregnancy and parenthood, perceptions of pregnancy risk
      and perceptions of the costs and benefits of using contraception. Further,
      motivation to use contraception fluctuated in different contexts, such as
      romantic relationships. CONCLUSIONS: Our research highlights the importance of
      attitudes toward contraception, pregnancy and parenthood in shaping teenagers'
      motivation to use contraception. Educational and prevention programs must address
      the spectrum of attitudes underlying teenagers' contraceptive and reproductive
      decisions in order to alter pathways to teenage pregnancy and early parenting.

PMID- 19179130
TI  - EUS 2008 Working Group document: interventional EUS--a road map for the future.

PMID- 19179131
TI  - Submucosal lesions.

PMID- 19179132
TI  - Pancreatic masses.

PMID- 19179133
TI  - Pancreatic cysts.

PMID- 19179134
TI  - Chronic pancreatitis.

PMID- 19179135
TI  - Linear array EUS in bile-duct lesions.

PMID- 19179136
TI  - Basic technique of FNA.

PMID- 19179137
TI  - EUS 2008 Working Group document: evaluation of EUS-guided drainage of pancreatic
      fluid collections (with video).

PMID- 19179138
TI  - Tricks for improving EUS-FNA accuracy and maximizing cellular yield.

PMID- 19179139
TI  - How I do it and when I use (and do not use) EUS-FNA.

PMID- 19179140
TI  - Needles: what is available, does size matter?

PMID- 19179141
TI  - Techniques for getting to difficult places.

PMID- 19179142
TI  - What I need to know and what I need to do if I do not have a cytopathologist
      present for the procedure.

PMID- 19179143
TI  - Technique of pancreatic cyst aspiration.

PMID- 19179144
TI  - Micrometastasis, molecular markers, and their future role with EUS-guided FNA.

PMID- 19179145
TI  - Imaging alone is sufficient in most circumstances--making the case for limited
      need for FNA.

PMID- 19179146
TI  - Imaging is overrated: early and frequent use of FNA in pancreatic tumors.

PMID- 19179147
TI  - The radial echoendoscope: here to stay or gone tomorrow?

PMID- 19179148
TI  - Basic technique for celiac plexus block/neurolysis.

PMID- 19179149
TI  - New approaches, including targeting the ganglia.

PMID- 19179150
TI  - What is the evidence for EUS-guided celiac plexus block/neurolysis?

PMID- 19179151
TI  - State of the art: putting EUS-guided block/neurolysis into perspective.

PMID- 19179153
TI  - Advanced techniques for drainage of peripancreatic fluid collections.

PMID- 19179152
TI  - EUS followed by endoscopic pancreatic pseudocyst drainage or all-in-one
      procedure: a review of basic techniques (with video).

PMID- 19179154
TI  - Endoscopic treatment of pancreatic fluid collections in 2008 and beyond.

PMID- 19179155
TI  - Technique and status of EUS-guided fine-needle injection.

PMID- 19179156
TI  - EUS-guided choledochoduodenostomy.

PMID- 19179157
TI  - Review of EUS-guided pancreatic duct drainage (with video).

PMID- 19179158
TI  - The use of EUS to diagnose cystic neoplasms of the pancreas.

PMID- 19179159
TI  - EUS and natural orifice transluminal endoscopic surgery.

PMID- 19179160
TI  - EUS-guided tumor ablation with heat, cold, microwave, or radiofrequency: will
      there be a winner?

PMID- 19179161
TI  - EUS: state of the art in the USA.

PMID- 19179162
TI  - EUS 2008 Working Group document: evaluation of EUS-guided pancreatic-cyst
      ablation.

PMID- 19179163
TI  - EUS: state of the art in Europe.

PMID- 19179164
TI  - EUS: state of the art in Asia.

PMID- 19179165
TI  - EUS 2008 Working Group document: evaluation of EUS-guided celiac plexus
      neurolysis/block (with video).

PMID- 19179166
TI  - EUS 2008 Working Group document: evaluation of EUS-guided hepaticogastrostomy.

PMID- 19179167
TI  - EUS 2008 Working Group document: evaluation of EUS-guided drainage of pelvic
      fluid collections (with video).

PMID- 19179168
TI  - EUS 2008 Working Group document: evaluation of EUS-guided vascular therapy.

PMID- 19179169
TI  - EUS 2008 Working Group document: evaluation of EUS-guided pancreatic-duct
      drainage (with video).

PMID- 19179170
TI  - EUS 2008 Working Group document: evaluation of EUS-guided implantation therapy
      (with video).

PMID- 19179171
TI  - EUS 2008 Working Group document: evaluation of EUS-guided injection therapy for
      tumors.

PMID- 19179172
TI  - EUS 2008 Working Group document: evaluation of EUS-guided tumor ablation.

PMID- 19179173
TI  - Basic functions of linear EUS processor and when to use them.

PMID- 19179174
TI  - Advanced imaging options: what is available?

PMID- 19179175
TI  - EUS contrast agents: what is available, how do they work, and are they effective?

PMID- 19179176
TI  - Basic technique of handling the linear echoendoscope and how it differs from the
      radial echoendoscope.

PMID- 19179177
TI  - EUS 2008 Working Group document: evaluation of EUS-guided choledochoduodenostomy
      (with video).

PMID- 19179178
TI  - The mediastinum.

PMID- 19179179
TI  - Curved linear array EUS technique in the pancreas and biliary tree: focusing on
      the stations.

PMID- 19179180
TI  - The gut: esophagus, stomach, and rectum.

PMID- 19179181
TI  - Esophageal cancer.

PMID- 19179182
TI  - EUS for mediastinal disease.

PMID- 19179184
TI  - Introduction: unknown primary cancer.

PMID- 19179185
TI  - Pathologic evaluation of unknown primary cancer.
AB  - The pathologic approach to metastases of unknown primary cancer (UPC) is stepwise
      and uses the clinical context, morphology, and, where necessary,
      immunohistochemistry (IHC). This review covers the initial approach to a UPC
      biopsy; the diagnosis of malignancy and broad tumor typing into carcinoma,
      melanoma, lymphoma, or sarcoma; and further subtyping of carcinoma into germ cell
      (broadly included), squamous, neuroendocrine, and solid organ including liver and
      renal, and adenocarcinomas. Finally, for adenocarcinoma, the prediction of
      primary tumor site, including lung, pancreas, stomach, colon, ovary, prostate,
      and breast, is discussed. For each tumor type, the morphologic features are
      presented alongside established useful IHC markers, with a description of their
      staining patterns and common diagnostic dilemmas. Optimal tissue handling and IHC
      interpretation, quality assurance, and limitations also are discussed. The target
      readership is oncologists, but other clinicians and trainee pathologists also may
      find the content of use.

PMID- 19179186
TI  - Molecular classification of unknown primary cancer.
AB  - The diagnosis of unknown primary carcinoma is often the result of the failure of
      light microscopy and immunohistochemistry to elucidate the origin of
      adenocarcinoma or poorly differentiated carcinoma. Recent advances in gene
      expression profiling using either reverse transcription polymerase chain reaction
      (RT-PCR) or microarray have enabled researchers to develop expression profiles
      unique to a wide variety of well-characterized primary cancers and to compare
      these unique signatures with those from unknown primary cancers. As the gene
      expression profile is frequently conserved when the tumor metastasizes, it is
      often possible to analyze a biopsy specimen and genomically identify its tissue
      of origin. In fact, the overall accuracy of genomic cancer classification in
      patients with known primary cancers is 80% to 90%. This new system of molecular
      classification might be considered as "genomic taxonomy." The genomic
      classification is then available to the pathologist and clinician to aid in both
      the patient's diagnosis and treatment planning. The impact of this new technology
      on patient outcomes is currently under study.

PMID- 19179187
TI  - Treatment for patients with unknown primary cancer and favorable prognostic
      factors.
AB  - Patients with carcinoma of unknown primary site are heterogeneous with respect to
      clinical and pathologic features. Within this diverse group, specific clinical
      and/or pathologic features can be used to define several subsets with favorable
      prognoses. Specific subsets include women with peritoneal carcinomatosis, women
      with isolated axillary lymph node metastases, adenocarcinoma presenting as a
      single metastatic lesion, young men with features of extragonadal germ cell
      tumor, squamous carcinoma involving cervical or inguinal lymph nodes, and
      neuroendocrine carcinoma. Prospective identification of patients in these
      favorable subgroups allows the most effective treatment to be selected. This
      review summarizes current recommendations for the evaluation and treatment of
      patients in each of these favorable prognostic subsets.

PMID- 19179188
TI  - Neuroendocrine carcinoma of unknown primary site.
AB  - Neuroendocrine carcinomas of unknown primary site are uncommon, diverse tumors
      with variable clinical behavior, predicted by tumor grade or differentiation.
      Most of these carcinomas probably arise from an occult/clinically undetectable
      primary site in one of several locations (bronchus, pancreas, stomach, colon,
      rectum and several other sites). Patients with these tumors are a subset of
      unknown primary carcinoma with relatively favorable prognoses. Low-grade or well
      differentiated tumors are frequently indolent and cases should be managed similar
      to advanced carcinoid tumors. Targeted therapies may have a role in the treatment
      of low-grade tumors. The high-grade or poorly differentiated carcinomas,
      including small cell and large cell neuroendocrine tumors, are rapidly growing
      and aggressive but responsive to platinum-based combination chemotherapy. Poorly
      differentiated large cell neuroendocrine tumors, first reported in 1988, are
      usually not recognized by routine hematoxylin and eosin light microscopy but
      require immunohistochemical stains or electron microscopy for their diagnosis. A
      review of cytotoxic chemotherapy for patients with high-grade neuroendocrine
      carcinomas, including a series of 99 patients, revealed an overall response rate
      of 70%, with a 20% complete response rate. The median survival was 15 months, and
      a minority of patients (13%) had long-term survival. Tumor grade/differentiation
      currently is an important determinant of the management of these patients, and
      therapy in the future will be based on a more precise knowledge of the unique
      biology of these tumors.

PMID- 19179189
TI  - Prognostic factors in unknown primary cancer.
AB  - In patients with unknown primary cancer, the diagnostic uncertainty as to the
      nature of the primary cancer also affects the formulation of a prognosis. Only in
      a minority of patients, the similarity of the clinical presentations to those of
      known primary cancers at a similar stage has resulted in the identification of
      subsets of patients with favorable clinical and pathological features. Their
      recognition is of major importance since specific treatment guidelines may
      translate into prolonged survival. For the vast majority of patients with unknown
      primary cancer and unfavorable outcome features, the identification of reliable
      prognostic indicators has proven challenging. A number of studies with
      multivariate analyses identified poor performance status, liver metastases, and
      abnormal serum lactic dehydrogenase (LDH) levels as the main recurrent adverse
      prognostic factors. No international consensus has been defined. The knowledge of
      prognostic factors may help the oncologist to refine the daily management of
      patients, to assess the results of clinical trials, and to design more useful
      clinical research studies.

PMID- 19179190
TI  - Treatment for patients with unknown primary carcinoma and unfavorable prognostic
      factors.
AB  - The treatment for patients with unknown primary carcinoma, particularly those
      with unfavorable prognosis factors, has changed in the last decade, and continues
      to evolve. Empiric chemotherapy trials reported since 2000 with the newer drugs
      have improved the overall survival compared to retrospective historical data and
      prospective clinical trials reported from 1967 to 2000. Long-term survival (1, 2,
      3 years and beyond) has been documented for a small minority of patients by
      several recent clinical trials. The survival of patients with a number of other
      advanced adenocarcinomas of known primary sites (colon, rectum, lung, pancreas)
      has been improved by the use of chemotherapy alone or combined with targeted
      drugs (bevacizumab, erlotinib), and about 60% of the patients with unknown
      primary adenocarcinomas harbor occult lesions of the colon, rectum, lung, or
      pancreas. Many of these patients have benefited from the newer broad-spectrum
      chemotherapy regimens. Several of these regimens appear about the same and
      currently represent the treatment of choice for the majority of these patients.
      Improvements in diagnostic pathology and molecular characterization of these
      carcinomas are likely to soon help select more appropriate and tailored therapies
      for many of these patients.

PMID- 19179191
TI  - Overview of patient management and future directions in unknown primary
      carcinoma.
AB  - The management of patients with unknown primary carcinoma (UPC) has evolved over
      the last few years and the recently developed sophisticated diagnostic modalities
      and novel therapies present both an opportunity for and a challenge to treatment
      of patients with this heterogeneous group of neoplasms. Recognition of patients
      with favorable prognostic factors is critical as specific therapies benefit these
      patients. Current empiric chemotherapy can offer a minority of patients with
      unfavorable prognostic factors substantial clinical benefit and improved
      survival. A focused search for the primary cancer is recommended in most
      patients. With the emergence of robust immunohistochemical stains and the growing
      field of molecular profiling, there is an increasing need for validation of a
      tailored approach to therapy. Our current focus is to study the impact of genetic
      profiling studies on patient outcomes and understand the limitations of currently
      available diagnostic studies. Although there are barriers to progress including
      tumor heterogeneity, challenging study designs, concerns with patient sample
      size, and inadequate research support, it is now important that an approach
      tailored to unknown primary subsets defined by the combination of clinical
      features, immunohistochemical stains, and molecular profiling be rigorously
      evaluated.

PMID- 19179192
TI  - Technical essentials of hepatic Doppler sonography.
AB  - Doppler ultrasound is an important diagnostic tool for detecting hepatic vascular
      abnormalities, especially following liver transplantation. Doppler ultrasound has
      an advantage over computed tomography or other imaging modalities in that it is
      noninvasive, can be used intraoperatively or immediately postoperatively at the
      patient's bedside, and is free from radiation hazard. Doppler ultrasound is also
      sensitive to very slow flow and is not limited by an optimal temporal window
      because it is a real-time examination. However, this examination is highly
      operator-dependent. For a proper evaluation of patient hemodynamic status,
      optimization of Doppler parameters and liberal use of spectral analysis will help
      prevent misinterpretation and may lead to improved diagnostic accuracy.
      Therefore, it is important for a radiologist to keep in mind a perspective on
      basic principle of Doppler phenomenon and tips in practical applications. In this
      article, we present a comprehensive review of Doppler ultrasound, emphasizing the
      basics and technical tips in clinical applications.

PMID- 19179193
TI  - Microwave ablation technology: what every user should know.
AB  - Microwave ablation is a relatively new technology under development and testing
      to treat the same types of cancer that can be treated with radiofrequency
      ablation. Microwave energy has several possible benefits over radiofrequency
      energy for tumor ablation but, because clinical microwave ablation systems are
      not widespread, the underlying principles and technologies may not be as
      familiar. The basic microwave ablation system contains many of the same
      components as a radiofrequency ablation system: a generator, a power distribution
      system, and an interstitial applicator. This article attempts to provide an
      overview of each of these components, outline their functions and roles, and
      provide some insight into what every potential microwave ablation user should
      know about systems in development.

PMID- 19179194
TI  - Practical applications of nuclear medicine in imaging breast cancer.
AB  - The rise in incidence, morbidity, and mortality of breast cancer has triggered
      multiple imaging efforts to detect this malignancy early, stage it accurately,
      and monitor it with precision in the posttherapeutic course. Among different
      imaging modalities, nuclear medicine provides an important contribution to the
      clinical management of breast cancer. This article discusses four practical
      applications based on the use of radionuclides in the evaluation of breast
      malignancy, focusing on scintimammography, preoperative tumor localization
      procedure using radioactive seeds, sentinel nodal scintigraphy, and F-18
      fluorodeoxyglucose positron emission tomography/computed tomography.

PMID- 19179195
TI  - Multidetector computed tomography of the mesocolon: review of anatomy and
      pathology.
AB  - The anatomy of the mesocolon can be seen on multidetector computed tomography
      (MDCT) scans, and its most important anatomic landmarks are the mesocolic
      vessels. The high spatial resolution of the current generation scanner coupled
      with the ability to generate high quality multiplanar images is very helpful in
      the delineation of the mesocolon. These vessels include the ileocolic and right
      colic vessels for the ascending mesocolon, the middle colic vessels for the
      transverse mesocolon, and the inferior mesenteric vein for the sigmoid and
      descending mesocolon. Knowledge of the anatomic landmarks of the mesocolon can
      help the radiologist identify the pathways for the spread of diseases of the
      colon and pancreas. Abnormalities of the mesocolon may also herald primary
      disease in the adjacent viscera. In the current context, this knowledge of the
      anatomy of the mesocolon and vascular landmarks can also be helpful for surgical
      planning, especially for minimal access or laparoscopic surgery.

PMID- 19179196
TI  - Magnetic resonance arthrography of superior labrum anterior-posterior lesions: a
      practical approach to interpretation.
AB  - Superior labrum anterior and posterior (SLAP) lesions are well-evaluated with
      magnetic resonance (MR) arthrography. This article discusses a practical approach
      to interpretation of MR arthrography exams for the evaluation of suspected SLAP
      lesions.

PMID- 19179197
TI  - Tricuspid regurgitation in mitral valve disease incidence, prognostic
      implications, mechanism, and management.
AB  - Tricuspid regurgitation (TR) in patients with mitral valve (MV) disease is
      associated with poor outcome and predicts poor survival, heart failure, and
      reduced functional capacity. It is common if left untreated after MV replacement
      mainly in rheumatic patients, but it is also common in patients with ischemic
      mitral regurgitation. It is less common, however, in those with degenerative
      mitral regurgitation. It might appear many years after surgery and might not
      resolve after correcting the MV lesion. Late TR might be caused by prosthetic
      valve dysfunction, left heart disease, right ventricular (RV) dysfunction and
      dilation, persistent pulmonary hypertension, chronic atrial fibrillation, or by
      organic (mainly rheumatic) tricuspid valve disease. Most commonly, late TR is
      functional and isolated, secondary to tricuspid annular dilation. Outcome of
      isolated tricuspid valve surgery is poor, because RV dysfunction has already
      occurred at that point in many patients. MV surgery or balloon valvotomy should
      be performed before RV dysfunction, severe TR, or advanced heart failure has
      occurred. Tricuspid annuloplasty with a ring should be performed at the initial
      MV surgery, and the tricuspid annulus diameter (>or=3.5 cm) is the best criterion
      for performing the annuloplasty. In this article we will review the current data
      available for understanding the prognostic implications, mechanism, and
      management of TR in patients with MV disease.

PMID- 19179198
TI  - Survival and neurologic recovery in patients with ST-segment elevation myocardial
      infarction resuscitated from cardiac arrest.
AB  - OBJECTIVES: We examined outcomes of patients resuscitated from cardiac arrest
      owing to ST-segment elevation myocardial infarction (STEMI) and predictors of
      survival and neurologic recovery. BACKGROUND: Immediately after resuscitation
      from cardiac arrest owing to STEMI, many patients show signs of neurologic
      impairment, and benefits of percutaneous coronary intervention and subsequent
      prognosis are not well defined. METHODS: Between January 1, 2002, and December
      31, 2006, we retrospectively identified consecutive patients resuscitated from
      cardiac arrest, regardless of time to return of spontaneous circulation (ROSC)
      and neurologic status, and reviewed the outcomes of those who had STEMI.
      Mortality and neurologic recovery at discharge and long-term mortality were
      assessed by individual chart review for those who underwent emergent angiography.
      RESULTS: Our study population consisted of 98 patients; 64% survived to
      discharge, and 92% had a full neurologic recovery. Predictors of survival were
      shorter time to ROSC, younger age, neurologic status post-resuscitation (alert or
      minimally responsive), and male sex. Predictors of neurologic recovery included
      shorter time to ROSC, neurologic status post-resuscitation (alert or minimally
      responsive), and younger age. Ninety-six percent of patients who were alert post
      resuscitation survived. Ninety-three percent of patients who were minimally
      responsive post-resuscitation survived. Fifty-nine patients were unresponsive
      post-resuscitation, with 44% survival, of whom 88% had full neurologic recovery.
      In the unresponsive group, unwitnessed arrest, prolonged ROSC, and older age were
      associated with increased risk of death, and older age and prolonged ROSC
      predicted poor neurologic recovery. CONCLUSIONS: When resuscitated patients with
      STEMI are being evaluated in the emergency department, serious consideration
      should be given to emergent angiography and revascularization, regardless of
      neurologic status.

PMID- 19179199
TI  - Hospital variation and characteristics of implantable cardioverter-defibrillator
      use in patients with heart failure: data from the GWTG-HF (Get With The
      Guidelines-Heart Failure) registry.
AB  - OBJECTIVES: The aim of this study was to describe hospital variation and factors
      associated with adherence to guidelines for implantable cardioverter
      defibrillator (ICD) therapy. BACKGROUND: Studies have shown incomplete
      application of ICD therapy in eligible heart failure (HF) patients. METHODS: New
      or discharge prescription rates for ICD therapy (ejection fraction <or=30%
      without documented ICD contraindications) for hospitals were calculated from
      participants in the GWTG-HF (Get With The Guidelines-Heart Failure) registry
      during January 2005 to June 2007. With hierarchical modeling, hospitals' patient
      case-mix adjusted ICD rate and hospital factors associated with ICD use were
      determined. The association of ICD rate and other quality of care indicators and
      procedure use was determined. RESULTS: Overall use of ICD in-hospital or planned
      implantation rate was 20%. This rate ranged widely among hospitals, from 1% among
      the lowest tertile to 35% among the top tertile (p < 0.01). After adjusting for
      patient case mix, independent hospital characteristics associated with higher ICD
      use were percutaneous coronary intervention, coronary artery bypass grafting, and
      heart transplant capability as well as larger hospital bed size (p < 0.01).
      Hospital Centers for Medicare and Medicaid Services/Joint Commission on the
      Accreditation of Healthcare Organizations performance measures (discharge
      instructions, angiotensin-converting enzyme inhibitor/angiotensin II receptor
      blocker use, smoking cessation; p >or= 0.05) were similar across ICD, whereas
      higher ICD-rate hospitals had higher adherence to GWTG-HF performance measures
      (beta-blocker use, evidence-based beta-blocker use, aldosterone-antagonist,
      hydralazine/nitrate; p < 0.05) except warfarin in patients with atrial
      fibrillation (p = 0.18). CONCLUSIONS: There is significant unexplained hospital
      variation in the use of ICD therapy among potentially eligible HF patients.
      However, hospitals that use ICD therapy more often also have more rapidly adopted
      other newer evidence-based HF therapies.

PMID- 19179200
TI  - Performance feedback: a common thread in the process to provide optimal heart
      failure care.

PMID- 19179201
TI  - Cardiac iodine-123 metaiodobenzylguanidine imaging predicts sudden cardiac death
      independently of left ventricular ejection fraction in patients with chronic
      heart failure and left ventricular systolic dysfunction: results from a
      comparative study with signal-averaged electrocardiogram, heart rate variability,
      and QT dispersion.
AB  - OBJECTIVES: We prospectively compared the predictive value of cardiac iodine-123
      metaiodobenzylguanidine (MIBG) imaging for sudden cardiac death (SCD) with that
      of the signal-averaged electrocardiogram (SAECG), heart rate variability (HRV),
      and QT dispersion in patients with chronic heart failure (CHF). BACKGROUND:
      Cardiac MIBG imaging predicts prognosis of CHF patients. However, the long-term
      predictive value of MIBG imaging for SCD in this population remains to be
      elucidated. METHODS: At entry, cardiac MIBG imaging, SAECG, 24-h Holter
      monitoring, and standard 12-lead electrocardiography (ECG) were performed in 106
      consecutive stable CHF outpatients with a radionuclide left ventricular ejection
      fraction (LVEF) <40%. The cardiac MIBG washout rate (WR) was obtained from MIBG
      imaging. Furthermore, the time and frequency domain HRV parameters were
      calculated from 24-h Holter recordings, and QT dispersion was measured from the
      12-lead ECG. RESULTS: During a follow-up period of 65 +/- 31 months, 18 of 106
      patients died suddenly. A multivariate Cox analysis revealed that WR and LVEF
      were significantly and independently associated with SCD, whereas the SAECG, HRV
      parameters, or QT dispersion were not. Patients with an abnormal WR (>27%) had a
      significantly higher risk of SCD (adjusted hazard ratio: 4.79, 95% confidence
      interval: 1.55 to 14.76). Even when confined to the patients with LVEF >35%, SCD
      was significantly more frequently observed in the patients with than without an
      abnormal WR (p = 0.02). CONCLUSIONS: Cardiac MIBG WR, but not SAECG, HRV, or QT
      dispersion, is a powerful predictor of SCD in patients with mild-to-moderate CHF,
      independently of LVEF.

PMID- 19179202
TI  - Multislice computed tomography in infective endocarditis: comparison with
      transesophageal echocardiography and intraoperative findings.
AB  - OBJECTIVES: The aim of this study was to assess the value of multislice computed
      tomography (CT) for the assessment of valvular abnormalities in patients with
      infective endocarditis (IE) in comparison with transesophageal echocardiography
      (TEE) and intraoperative findings. BACKGROUND: Multislice CT has recently shown
      promising data regarding valvular imaging in a 4-dimensional fashion. METHODS:
      Thirty-seven consecutive patients with clinically suspected IE were examined with
      TEE and 64-slice CT or dual-source CT. Twenty-nine patients had definite IE and
      underwent surgery. RESULTS: The diagnostic performance of CT for the detection of
      evident valvular abnormalities for IE compared with TEE was: sensitivity 97%,
      specificity 88%, positive predictive value (PPV) 97%, and negative predictive
      value (NPV) 88% on a per-patient basis (n = 37; excellent intermodality agreement
      kappa = 0.84). CT correctly identified 26 of 27 (96%) patients with valvular
      vegetations and 9 of 9 (100%) patients with abscesses/pseudoaneurysms compared
      with the intraoperative specimen. On a per-valve-based analysis, diagnostic
      accuracy for the detection of vegetations and abscesses/pseudoaneurysms compared
      with surgery was: sensitivity 96%, specificity 97%, PPV 96%, NPV 97%, and
      sensitivity 100%, specificity 100%, PPV 100%, NPV 100%, respectively, without
      significant differences as compared with TEE. Vegetation size measurements by CT
      correlated (r = 0.95; p <0.001) with TEE (mean 7.6 +/- 5.6 mm). The mobility of
      vegetations was accurately diagnosed in 21 of 22 (96%) patients with CT, but all
      of 4 leaflet perforations (<or=2 mm) were missed. CT provided more accurate
      anatomic information regarding perivalvular extent of abscess/pseudoaneurysms
      than TEE. CONCLUSIONS: Multislice CT shows good results in detecting valvular
      abnormalities in IE and could be applied in pre-operative planning and exclusion
      of coronary artery disease before surgery.

PMID- 19179203
TI  - Blood pressure response under chronic antihypertensive drug therapy: the role of
      aortic stiffness in the REASON (Preterax in Regression of Arterial Stiffness in a
      Controlled Double-Blind) study.
AB  - OBJECTIVES: We sought to evaluate the role of arterial stiffness on blood
      pressure (BP) response to drug treatment. BACKGROUND: Increased arterial
      stiffness (pulse wave velocity [PWV]) is associated with increased systolic blood
      pressure (SBP). Antihypertensive drug therapy achieves better control of
      diastolic blood pressure (DBP) than SBP does, implying that increased PWV might
      be a predictor of the SBP response to treatment. METHODS: The REASON (Preterax in
      Regression of Arterial Stiffness in a Controlled Double-Blind) study is a
      randomized, double-blind trial comparing atenolol versus perindopril/indapamide;
      375 patients with hypertension, with BP and PWV measurements at baseline and
      after 12 months of treatment, were divided into 3 tertiles according to baseline
      PWV and included in a post-hoc analysis. RESULTS: After 12 months of treatment,
      BP differed significantly between PWV tertiles (the third having the lowest
      response, p < 0.05). Factors related to smaller BP decline were low baseline BP,
      high baseline PWV, need for a double dose of treatment, use of atenolol (only for
      SBP response), and age (only for DBP). Although DBP control did not differ in the
      PWV tertiles, SBP control was significantly associated with PWV level (p = 0.001)
      as well as with the use of perindopril/indapamide (p < 0.001). The predictive
      value of PWV on BP response was independent of age, sex, mean BP, and
      cardiovascular risk factors. CONCLUSIONS: Baseline PWV is a significant predictor
      of BP response to antihypertensive treatment, independent from age, the need for
      increasing drug dosage, and the presence of cardiovascular risk factors.
      Achievement of SBP control appears to be influenced by aortic stiffness as well
      as by angiotensin-converting enzyme inhibition.

PMID- 19179204
TI  - The aorta and resistant hypertension.

PMID- 19179205
TI  - Single coronary artery.

PMID- 19179206
TI  - Cardiac magnetic resonance imaging and coronary computed tomography angiography
      in the diagnosis of anomalous coronary artery.

PMID- 19179207
TI  - Impact of diastolic dysfunction on heart failure-related hospitalizations.

PMID- 19179209
TI  - Elevated N-terminal pro-B-type natriuretic peptide levels: the effect of chronic
      obstructive pulmonary disease.

PMID- 19179211
TI  - Insulin as a cardiovascular therapeutic: improving glycemic control in patients
      with coronary artery disease.

PMID- 19179212
TI  - Insulin as an anti-inflammatory and antiatherogenic modulator.
AB  - Data demonstrate the anti-inflammatory effects of insulin and proinflammatory
      effects of glucose. These data provide a mechanistic justification for the
      benefits of maintaining euglycemia with insulin infusions in hospitalized
      patients. Regimens that infuse fixed doses of insulin with high rates of glucose
      are usually associated with hyperglycemia, which may neutralize the beneficial
      effects of insulin. Therefore, we propose that such regimens should be avoided
      and instead replaced by insulin infusions that normalize and maintain blood
      glucose at a reasonably low level and ensure that plasma insulin is maintained at
      levels high enough to provide clinically relevant anti-inflammatory and
      cardioprotective effects. Trials to test this hypothesis are in progress.

PMID- 19179213
TI  - Defining the role of basal and prandial insulin for optimal glycemic control.
AB  - Type 2 diabetes mellitus is a progressive disease characterized by early
      impairment of beta-cell function and ultimately loss of beta-cell mass. Hence, a
      single daily injection of a long-acting insulin is commonly initiated after
      intensification of oral antihyperglycemic therapy. Hemoglobin A1C should be
      measured every 3 months and therapy adjusted if the target is not met. As beta
      cell function continues to decline, it is often necessary to add exogenous bolus
      insulin therapy, using short-acting insulin analogs or regular insulin.
      Alternatively, the use of pre-mixed insulin preparations, combining both long
      acting and short-acting insulins, may be used.

PMID- 19179214
TI  - Cardiovascular therapies and associated glucose homeostasis: implications across
      the dysglycemia continuum.
AB  - Certain cardiovascular drugs have adverse effects on glucose homeostasis, which
      may lead to important long-term implications for increased risks of adverse
      outcomes. Thiazide diuretics, niacin, and beta-adrenergic blockers impair glucose
      homeostasis. However, angiotensin-converting enzyme inhibitors and angiotensin
      receptor blockers have demonstrated beneficial metabolic effects. The newer
      vasodilating beta-blocking agents and calcium antagonists appear to be
      metabolically neutral. These considerations, in addition to meticulous attention
      to blood pressure control and lifestyle changes, have the potential to
      beneficially modify glycemia and long-term risks. These considerations have
      particular importance in younger patients who may also have pre-diabetes or the
      metabolic syndrome and who are likely to require therapy over the course of
      decades.

PMID- 19179215
TI  - Coronary circulatory function abnormalities in insulin resistance: insights from
      positron emission tomography.
AB  - Traditionally, assessment of coronary circulatory function has been complex,
      requiring invasive techniques, including quantitative coronary angiography,
      intracoronary flow velocity probes, and pharmacologic stressor agents. However,
      radiotracer-based techniques for noninvasive measurement of myocardial blood flow
      are now available. Studies using these new techniques demonstrate that insulin
      resistance is associated with functional disturbances of the coronary
      circulation. Conversely, insulin infusion improves coronary flow, even in the
      setting of type 2 diabetes mellitus and coronary artery disease.

PMID- 19179217
TI  - Lowering glucose to prevent adverse cardiovascular outcomes in a critical care
      setting.
AB  - High admission blood glucose levels after acute myocardial infarction are common
      and associated with an increased risk of death in patients with or without
      diabetes. Hyperglycemia is associated with altered myocardial blood flow and
      energetics and can lead to a pro-oxidative/proinflammatory state. The use of
      intensive insulin treatment has shown superior benefits in the treatment of
      hyperglycemia versus glucose-insulin-potassium infusion, particularly in critical
      care settings.

PMID- 19179218
TI  - A new dawn for global health?

PMID- 19179216
TI  - The pathologic continuum of diabetic vascular disease.
AB  - Hyperglycemia can promote vascular complications by multiple mechanisms, with
      formation of advanced glycation end products and increased oxidative stress
      proposed to contribute to both macrovascular and microvascular complications.
      Many of the earliest pathologic responses to hyperglycemia are manifest in the
      vascular cells that directly encounter elevated blood glucose levels. In the
      macrovasculature, these include endothelial cells and vascular smooth muscle
      cells. In the microvasculature, these include endothelial cells, pericytes (in
      retinopathy), and podocytes (in renal disease). Additionally, neovascularization
      arising from the vasa vasorum may promote atherosclerotic plaque progression and
      contribute to plaque rupture, thereby interconnecting macroangiopathy and
      microangiopathy.

PMID- 19179220
TI  - Herpes simplex virus and HIV-1: deciphering viral synergy.

PMID- 19179221
TI  - Leishmania donovani leishmaniasis in Cyprus.

PMID- 19179222
TI  - Vaccine immunogenicity in injecting drug users.

PMID- 19179223
TI  - Lancet conference on healthcare-associated infections.

PMID- 19179224
TI  - Will a sledgehammer always crack a nut?

PMID- 19179225
TI  - Use of PCR for diagnosis of invasive aspergillosis: systematic review and meta
      analysis.
AB  - A systematic review and meta-analysis was done on the use of PCR tests for the
      diagnosis of invasive aspergillosis. Data from more than 10000 blood, serum, or
      plasma samples obtained from 1618 patients at risk for invasive aspergillosis
      were retrieved from 16 studies. Overall, the mean diagnostic odds ratios (DORs)
      of PCR for proven and probable cases were similar whether two consecutive
      positive samples were required to define positivity (DOR 15.97 [95% CI 6.83
      37.34]) or a single positive PCR test was required (DOR 16.41 [95% CI 6.43
      41.88]). Sensitivity and specificity of PCR for two consecutive positive samples
      were 0.75 (95% CI 0.54-0.88) and 0.87 (95% CI 0.78-0.93), respectively, and if
      only a single positive sample was required, these values were 0.88 (95% CI 0.75
      0.94) and 0.75 (95% CI 0.63-0.84), respectively. Whereas specificity based on a
      single positive test was significantly lower (p=0.027) than two positive tests,
      the sensitivity and DOR did not differ significantly. A single PCR-negative
      result is thus sufficient to exclude a diagnosis of proven or probable invasive
      aspergillosis. However, two positive tests are required to confirm the diagnosis
      because the specificity is higher than that attained from a single positive test.
      Populations at risk varied and there was a lack of homogeneity of the PCR methods
      used. Efforts are underway to devise a standard for Aspergillus sp PCR for
      screening, which will help enable formal validation of PCR and estimate its use
      in patients most likely to benefit.

PMID- 19179226
TI  - Development of novel treatments for hepatitis C.
AB  - Hepatitis C virus (HCV) infection is a major and growing global health problem,
      affecting about 170 million people worldwide, and is a leading cause of liver
      cirrhosis and hepatocellular carcinoma. Currently, treatment is restricted to
      interferon alfa and ribavirin, which leads to a successful outcome in only about
      50% of individuals. New effective treatments with tolerable side-effect profiles
      are needed urgently, but development has been hindered by an inability to culture
      HCV and a scarcity of animal models. Herein, we review progress in HCV biology,
      including cell culture and new animal models, and the contribution of this work
      to our understanding of the virus' life-cycle and pathogenesis and development of
      specifically targeted antiviral treatment. We also discuss changes in our
      understanding of HCV epidemiology, clinical manifestations, and diagnostics.

PMID- 19179228
TI  - Staphylococcus aureus disease and drug resistance in resource-limited countries
      in south and east Asia.
AB  - By contrast with high-income countries, Staphylococcus aureus disease ranks low
      on the public-health agenda in low-income countries. We undertook a literature
      review of S aureus disease in resource-limited countries in south and east Asia,
      and found that its neglected status as a developing world pathogen does not
      equate with low rates of disease. The incidence of the disease seems to be
      highest in neonates, its range of clinical manifestations is as broad as that
      seen in other settings, and the mortality rate associated with serious S aureus
      infection, such as bacteraemia, is as high as 50%. The prevalence of meticillin
      resistant S aureus (MRSA) infection across much of resource-limited Asia is
      largely unknown. Antibiotic drugs are readily and widely available from
      pharmacists in most parts of Asia, where ease of purchase and frequent self
      medication are likely to be major drivers in the emergence of drug resistance. In
      our global culture, the epidemiology of important drug-resistant pathogens in
      resource-limited countries is inextricably linked with the health of both
      developing and developed communities. An initiative is needed to raise the
      profile of S aureus disease in developing countries, and to define a programme of
      research to find practical solutions to the health-care challenges posed by this
      important global pathogen.

PMID- 19179229
TI  - Chronic granulomatous Mycobacterium avium skin pseudotumour.

PMID- 19179230
TI  - Teleradiology: two-edged sword or friend of radiology practice?

PMID- 19179231
TI  - The world of molecular imaging.

PMID- 19179227
TI  - Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta
      analysis of observational studies.
AB  - We did a systematic review and meta-analysis of observational studies of the risk
      of HIV-1 transmission per heterosexual contact. 43 publications comprising 25
      different study populations were identified. Pooled female-to-male (0.04% per act
      [95% CI 0.01-0.14]) and male-to-female (0.08% per act [95% CI 0.06-0.11])
      transmission estimates in high-income countries indicated a low risk of infection
      in the absence of antiretrovirals. Low-income country female-to-male (0.38% per
      act [95% CI 0.13-1.10]) and male-to-female (0.30% per act [95% CI 0.14-0.63])
      estimates in the absence of commercial sex exposure (CSE) were higher. In meta
      regression analysis, the infectivity across estimates in the absence of CSE was
      significantly associated with sex, setting, the interaction between setting and
      sex, and antenatal HIV prevalence. The pooled receptive anal intercourse estimate
      was much higher (1.7% per act [95% CI 0.3-8.9]). Estimates for the early and late
      phases of HIV infection were 9.2 (95% CI 4.5-18.8) and 7.3 (95% CI 4.5-11.9)
      times larger, respectively, than for the asymptomatic phase. After adjusting for
      CSE, presence or history of genital ulcers in either couple member increased per
      act infectivity 5.3 (95% CI 1.4-19.5) times versus no sexually transmitted
      infection. Study estimates among non-circumcised men were at least twice those
      among circumcised men. Low-income country estimates were more heterogeneous than
      high-income country estimates, which indicates poorer study quality, greater
      heterogeneity of risk factors, or under-reporting of high-risk behaviour. Efforts
      are needed to better understand these differences and to quantify infectivity in
      low-income countries.

PMID- 19179232
TI  - Radiologists and the vanishing white coat.

PMID- 19179233
TI  - Health care in a time of peril.

PMID- 19179234
TI  - Yet more changes to the stark law regulations.

PMID- 19179236
TI  - Recent shifts in place of service for noninvasive diagnostic imaging: have
      hospitals missed an opportunity?
AB  - PURPOSE: The aim of this study was to examine recent shifts in place of service
      for noninvasive diagnostic imaging (NDI) and determine whether hospitals have
      lost business to private outpatient imaging facilities. METHOD AND MATERIALS: The
      nationwide Medicare Part B databases for 1996 through 2006 were used, and all
      Current Procedural Terminology((R)), fourth edition, codes for NDI were studied.
      Utilization rates per 1,000 Medicare beneficiaries were calculated. Medicare uses
      place-of-service codes to differentiate examinations performed in hospital
      inpatients, hospital outpatients, and hospital emergency departments from those
      performed in private office settings. Changes in utilization rates in these
      locations were compared over the course of the decade, with particular emphasis
      on possible outpatient NDI shifts between hospital outpatient departments and
      private offices or imaging centers. Also, Medicare physician specialty codes were
      used to determine whether radiologists or other specialists were more responsible
      for growth. RESULTS: Between 1996 and 2006, Medicare NDI utilization rates per
      1,000 -hospital inpatients increased from 1,056.5 to 1,211.8 (+15%). Emergency
      department rates increased from 222.1 to 392.2 (+77%). Hospital outpatient rates
      increased from 793.4 to 993.2 (+25%), while private office rates went from 883.3
      to 1,442.2 (+63%). Total outpatient imaging rates (both hospital and office) went
      from 1,676.7 to 2,435.4 (+45%). As a result of the more rapid growth in private
      office imaging, hospitals' share of this market dropped from 47% in 1996 to 41%
      in 2006. Private office imaging utilization rates between 1996 and 2006 grew by
      71% among nonradiologist physicians, compared with 44% among radiologists.
      CONCLUSION: Medicare NDI utilization rates increased in all places of service
      between 1996 and 2006. Growth in hospital outpatient imaging was slower than that
      in private imaging facilities. Because NDI can be a profitable business, it seems
      that hospitals have lost an important opportunity. Much of this loss of business
      was to nonradiologist physicians, whose private office imaging utilization rate
      grew considerably more rapidly than that of radiologists.

PMID- 19179235
TI  - ACR appropriateness criteria on nonsurgical treatment for non-small-cell lung
      cancer: poor performance status or palliative intent.
AB  - Radiation therapy (RT) plays a major role in the definitive treatment of patients
      with non-small-cell lung cancer who are unable to tolerate surgery. Radiation
      therapy alone is used primarily for early-stage (stages I and II) patients.
      Higher doses of RT (>65 Gy) seem to improve outcomes, and modern techniques such
      as stereotactic body RT have been very promising. For patients with locally
      advanced disease (stages IIIA and IIIB), concurrent chemotherapy and RT remains
      the standard of care. However, many patients cannot tolerate the regimen because
      of its toxicity. Sequential chemotherapy followed by RT is used in these
      situations. Radiation therapy alone is used for the rare patient who cannot
      tolerate the use of any chemotherapy because of comorbid conditions. Palliative
      external-beam RT is useful for patients with metastatic disease, causing symptoms
      such as dyspnea, cough, hemoptysis, postobstructive pneumonia, and pain.
      Hypofractionation has been attempted as a means to provide more rapid and
      convenient symptom relief, but results from clinical trials are conflicting on
      whether it is an improvement over standard palliative fractionation.
      Endobronchial brachytherapy provides relief for patients with endobronchial
      lesions causing obstruction or hemoptysis. Palliative chemotherapy improves
      survival and quality of life in patients with metastatic disease compared with
      best supportive care. Chemotherapy also improves outcomes as a second-line and
      third-line treatment for patients in whom previous regimens have failed. Biologic
      therapies such as erlotinib and bevacizumab have been incorporated into every
      phase of chemotherapy with good results.

PMID- 19179237
TI  - Keeping professionalism alive in radiology's new age: a choice; our future.
AB  - Professionalism in radiology is often talked about but seldom defined or formally
      instituted. Awareness of its value and adoption of its principles will be our
      best defense against the perils that lie ahead in radiology's new age.

PMID- 19179238
TI  - Improvement in radiology education: joint efforts of the American Board of
      Radiology and the Diagnostic Radiology Residency Review Committee.
AB  - The ABR and the Radiology Residency Review Committee have focused their joint
      efforts in the past three years to improve radiology education. The new structure
      and timing of the ABR certifying exams and proposed new training program
      requirement to support them exemplity the efforts to ensure that training
      relevant to the imaging needs of an increasingly subspecialized medical
      environment.

PMID- 19179239
TI  - The architecture of smart surveys: core issues in why and how to collect patient
      and referring physician satisfaction data.
AB  - Radiology practices are facing challenges on many fronts. As the field becomes
      more competitive, leaders must pay more attention to the quality of the service
      that groups provide to their customers. This need is also being driven by higher
      expectations from customers, particularly patients, who will likely act much more
      like consumers in the 21st century. For practices to succeed in providing
      exemplary service, they must pay attention to the voices of their key customer
      groups. It is dismaying to see practices that are struggling or even dissolving
      over issues created by poor service. As much as we are experts in imaging, we are
      unlikely to be able to provide superlative service by reading books, talking
      among ourselves, or hiring consultants. Rather, we must do what should be
      obvious, which is to actually ask our customers how we are doing. Surveys are one
      of the important tools that can be brought to bear on this issue. For many
      groups, surveying is the starting point for understanding what their patients,
      referring physicians, and other key stakeholders want. Groups can also find out
      what customers like and dislike about their experiences, and how groups compare
      with their competitors. This article provides a guide on how to get off to a good
      start in designing and deploying surveys that can help optimize the way groups
      take care of their patients and help their referring physicians.

PMID- 19179240
TI  - Bibliometric analysis of radiation oncology departmental scholarly publication
      productivity at domestic residency training institutions.
AB  - PURPOSE: Corporate scientific activity lies at the heart of the modern academic
      institution, and yet field-specific estimates of institutional or departmental
      scholarly productivity are difficult to assess. The authors sought to estimate
      long-term and current departmental research efforts at residency-sponsoring US
      radiation oncology departments, using modifications of established bibliometric
      indices. METHODS: Bibliometric citation database searches were performed for all
      residency-affiliated academic radiation oncology departments and their component
      physician radiation oncology faculty members. Metrics based on publication,
      citation, and the Hirsch index (h-index) were calculated, and departments were
      ranked by departmental productivity from 1996 to 2007, as well as by current mean
      faculty bibliometric output. RESULTS: Seventy-eight academic radiation oncology
      departments and their component 826 radiation oncologist faculty members were
      analyzed bibliometrically. The average number of publications per department from
      1996 to 2007 was 363.8, with a mean of 8,116.0 citations and a mean institutional
      h-index of 37.2. Departments at academic institutions demonstrated a grand mean
      of 41.0 publications, 709.0 citations, and an h-index of 7.6 as of fall 2007. A
      larger number of physician faculty members (>12) was associated with increased
      scholarly activity. CONCLUSIONS: The use of quantitative metrics provides
      departments and researchers with a mechanism to evaluate collective scientific
      productivity and serves as an impetus for improved performance across the field.

PMID- 19179241
TI  - Experience of an academic neuroradiology division participating in a utilization
      management program.
AB  - BACKGROUND AND PURPOSE: There has been a steady increase in the utilization of
      expensive outpatient imaging studies, with a resultant increase in health care
      costs. To reduce unnecessary and inappropriate studies, the authors' department
      has participated in a utilization management (UM) program; in this article, the
      authors report the experience of the division of neuroradiology. METHODS: Using
      evidence-based guidelines, a commercial UM program provides real-time decision
      support for physicians ordering expensive outpatient imaging studies. After
      consultation between UM personnel and a referring physician's staff, studies not
      meeting appropriateness criteria are referred to an academic radiologist for
      review. The radiologist can approve the study after reviewing the electronic
      chart or call the referring physician for further information. Studies are not
      denied by radiologists. RESULTS: For health plans of one large payer, 2,032
      neuroradiologic studies were reviewed by 7 neuroradiologists during a 1-year
      period, of which 1,622 (80%) were approved. The remaining 410 studies (20%) were
      initially withdrawn by consensus or by no callback. Overall, 293 of the 410 (71%)
      studies (208 magnetic resonance, 85 computed tomography) initially not performed
      were not reordered (duration of follow-up, 3-15 months). Hence, 293 of 2,032
      (14%) of all studies reviewed were not performed. The estimated cost of scans not
      performed was about $150,000. Approximately 6% of requests were changed to more
      appropriate studies. CONCLUSION: The participation of academic neuroradiologists
      in a UM program affected the performance of many expensive outpatient imaging
      studies. There was a durable reduction in unnecessary and inappropriate studies.
      These results demonstrate the utility of evidence-based appropriateness criteria
      in radiology UM programs and the power of the sentinel effect.

PMID- 19179242
TI  - IT tools will be critical in helping reduce radiation exposure from medical
      imaging.

PMID- 19179243
TI  - Multislice scanners and radiation dose.

PMID- 19179244
TI  - The heart of radiology.

PMID- 19179245
TI  - Traian Leucutia.

PMID- 19179246
TI  - Finding features for real-time premature ventricular contraction detection using
      a fuzzy neural network system.
AB  - Fuzzy neural networks (FNNs) have been successfully applied to generate
      predictive rules for medical or diagnostic data. This brief presents an approach
      to detect premature ventricular contractions (PVCs) using the neural network with
      weighted fuzzy membership functions (NEWFMs). The NEWFM classifies normal and PVC
      beats by the trained bounded sum of weighted fuzzy membership functions (BSWFMs)
      using wavelet transformed coefficients from the MIT-BIH PVC database. The eight
      generalized coefficients, locally related to the time signal, are extracted by
      the nonoverlap area distribution measurement method. The eight generalized
      coefficients are used for the three PVC data sets with reliable accuracy rates of
      99.80%, 99.21%, and 98.78%, respectively, which means that the selected features
      are less dependent on the data sets. It is shown that the locations of the eight
      features are not only around the QRS complex that represents ventricular
      depolarization in the electrocardiogram (ECG) containing a Q wave, an R wave, and
      an S wave, but also the QR segment from the Q wave to the R wave has more
      discriminate information than the RS segment from the R wave to the S wave. The
      BSWFMs of the eight features trained by NEWFM are shown visually, which makes the
      features explicitly interpretable. Since each BSWFM combines multiple weighted
      fuzzy membership functions into one using the bounded sum, the eight small-sized
      BSWFMs can realize real-time PVC detection in a mobile environment.

PMID- 19179247
TI  - Comparison between analog and digital neural network implementations for range
      finding applications.
AB  - A neural network (NN) was developed in order to increase the distance range of a
      phase-shift laser range finder and to achieve surface recognition, by using two
      photoelectrical signals issued from the measurement system. The NN architecture
      consists of a multilayer perceptron (MLP) with two inputs, three neurons in the
      hidden layer, and one output. Depending on the application, the NN output has to
      resolve the ambiguity due to phase-shift measurement by linearizing the inverse
      of the square law, or to indicate an output voltage corresponding to the tested
      surface. This embedded system dedicated to optoelectronic measurements was
      successfully tested with an analog NN, implemented in 0.35- microm complimentary
      metal-oxide-semiconductor (CMOS) technology, resulting in a threefold increase in
      the distance range with respect to the one limited by the phase-shift
      measurement, and by discriminating four types of surfaces (a plastic surface,
      glossy paper, a painted wall, and a porous surface), at a remote distance between
      the range finder and the target varying from 0.5 m up to 1.25 m and with a laser
      beam angle varying between -pi/6 and pi/6 with respect to the target. In this
      type of application, NN analog implementation provides many advantages, notably
      use of a small silicon area, low power consumption and no analog-to-digital
      conversions (ADCs). Nevertheless, digital implementation allows ease of
      conception and reconfigurability and an embedded weight and bias update. This
      paper presents the complete measurement system and a comparison between both
      types of implementation, by developing the advantages and drawbacks relative to
      each method. An optimized mixed architecture, using both techniques, is then
      proposed and discussed at the end of the paper.

PMID- 19179248
TI  - Kernel-matching pursuits with arbitrary loss functions.
AB  - The purpose of this research is to develop a classifier capable of state-of-the
      art performance in both computational efficiency and generalization ability while
      allowing the algorithm designer to choose arbitrary loss functions as appropriate
      for a give problem domain. This is critical in applications involving heavily
      imbalanced, noisy, or non-Gaussian distributed data. To achieve this goal, a
      kernel-matching pursuit (KMP) framework is formulated where the objective is
      margin maximization rather than the standard error minimization. This approach
      enables excellent performance and computational savings in the presence of large,
      imbalanced training data sets and facilitates the development of two general
      algorithms. These algorithms support the use of arbitrary loss functions allowing
      the algorithm designer to control the degree to which outliers are penalized and
      the manner in which non-Gaussian distributed data is handled. Example loss
      functions are provided and algorithm performance is illustrated in two groups of
      experimental results. The first group demonstrates that the proposed algorithms
      perform equivalent to several state-of-the-art machine learning algorithms on
      well-published, balanced data. The second group of results illustrates superior
      performance by the proposed algorithms on imbalanced, non-Gaussian data achieved
      by employing loss functions appropriate for the data characteristics and problem
      domain.

PMID- 19179249
TI  - Adaptive statistic tracking control based on two-step neural networks with time
      delays.
AB  - This paper presents a new type of control framework for dynamical stochastic
      systems, called statistic tracking control (STC). The system considered is
      general and non-Gaussian and the tracking objective is the statistical
      information of a given target probability density function (pdf), rather than a
      deterministic signal. The control aims at making the statistical information of
      the output pdfs to follow those of a target pdf. For such a control framework, a
      variable structure adaptive tracking control strategy is first established using
      two-step neural network models. Following the B-spline neural network
      approximation to the integrated performance function, the concerned problem is
      transferred into the tracking of given weights. The dynamic neural network (DNN)
      is employed to identify the unknown nonlinear dynamics between the control input
      and the weights related to the integrated function. To achieve the required
      control objective, an adaptive controller based on the proposed DNN is developed
      so as to track a reference trajectory. Stability analysis for both the
      identification and tracking errors is developed via the use of Lyapunov stability
      criterion. Simulations are given to demonstrate the efficiency of the proposed
      approach.

PMID- 19179250
TI  - Analysis of survival data having time-dependent covariates.
AB  - Cox's proportional hazards model has been widely used for the analysis of
      treatment and prognostic effects with censored survival data. In this paper, we
      propose a neural network model based on bootstrapping to estimate the survival
      function and predict the short-term survival at any time during the course of the
      disease. The bootstrapping for the neural network is introduced when selecting
      the optimum number of hidden units and testing the goodness-of-fit. The proposed
      methods are illustrated using data from a long-term study of patients with
      primary biliary cirrhosis (PBC).

PMID- 19179251
TI  - A new projection-based neural network for constrained variational inequalities.
AB  - This paper presents a new neural network model for solving constrained
      variational inequality problems by converting the necessary and sufficient
      conditions for the solution into a system of nonlinear projection equations. Five
      sufficient conditions are provided to ensure that the proposed neural network is
      stable in the sense of Lyapunov and converges to an exact solution of the
      original problem by defining a proper convex energy function. The proposed neural
      network includes an existing model, and can be applied to solve some nonmonotone
      and nonsmooth problems. The validity and transient behavior of the proposed
      neural network are demonstrated by some numerical examples.

PMID- 19179252
TI  - Constructing ensembles of classifiers by means of weighted instance selection.
AB  - In this paper, we approach the problem of constructing ensembles of classifiers
      from the point of view of instance selection. Instance selection is aimed at
      obtaining a subset of the instances available for training capable of achieving,
      at least, the same performance as the whole training set. In this way, instance
      selection algorithms try to keep the performance of the classifiers while
      reducing the number of instances in the training set. Meanwhile, boosting methods
      construct an ensemble of classifiers iteratively focusing each new member on the
      most difficult instances by means of a biased distribution of the training
      instances. In this work, we show how these two methodologies can be combined
      advantageously. We can use instance selection algorithms for boosting using as
      objective to optimize the training error weighted by the biased distribution of
      the instances given by the boosting method. Our method can be considered as
      boosting by instance selection. Instance selection has mostly been developed and
      used for k -nearest neighbor ( k -NN) classifiers. So, as a first step, our
      methodology is suited to construct ensembles of k -NN classifiers. Constructing
      ensembles of classifiers by means of instance selection has the important feature
      of reducing the space complexity of the final ensemble as only a subset of the
      instances is selected for each classifier. However, the methodology is not
      restricted to k-NN classifier. Other classifiers, such as decision trees and
      support vector machines (SVMs), may also benefit from a smaller training set, as
      they produce simpler classifiers if an instance selection algorithm is performed
      before training. In the experimental section, we show that the proposed approach
      is able to produce better and simpler ensembles than random subspace method (RSM)
      method for k-NN and standard ensemble methods for C4.5 and SVMs.

PMID- 19179253
TI  - Mode-kn Factor Analysis for image ensembles.
AB  - In this corespondence, we study the extra-factor estimation problem with the
      assumption that the training image ensemble is expressed as an nth-order tensor
      with the nth-dimension characterizing all features for an image and other
      dimensions for different extra factors, such as illuminations, poses, and
      identities. To overcome the local minimum issue of conventional algorithms
      designed for this problem, we present a novel statistical learning framework
      called mode-kn Factor Analysis for obtaining a closed-form solution to estimating
      the extra factors of any test image. In the learning stage, for the kth [see
      formula in text] dimension of the data tensor, the mode-kn patterns are
      constructed by concatenating the feature dimension and the kth extra-factor
      dimension, and then a mode-kn factor analysis model is learnt based on the mode
      kn patterns unfolded from the original data tensor. In the inference stage, for a
      test image, the mode classification of the kth dimension is performed within a
      probabilistic framework. The advantages of mode-kn factor analysis over
      conventional tensor analysis algorithms are twofold: 1) a closed-form solution,
      instead of iterative sub-optimal solution as conventionally, is derived for
      estimating the extra-factor mode of any test image; and 2) the classification
      capability is enhanced by interacting with the process of synthesizing data of
      all other modes in the k th dimension. Experiments on the Pointing'04 and CMU PIE
      databases for pose and illumination estimation both validate the superiority of
      the proposed algorithm over conventional algorithms for extra-factor estimation.

PMID- 19179254
TI  - Arranging and interpolating sparse unorganized feature points with geodesic
      circular arc.
AB  - A novel method to reconstruct object boundaries with geodesic circular arc is
      proposed in this paper. Within this framework, an energy of circular arc spline
      is utilized to simultaneously arrange and interpolate each member in the set of
      sparse unorganized feature points from the desired boundaries. A general form for
      a family of parametric circular arc spline is firstly derived and followed by a
      novel method of arranging these feature points by minimizing an energy term
      depending on the circular arc spline configuration defined on these feature
      points. With regard to the fact that the energy function is usually nonconvex and
      nondifferentiable at its critical points, an improved scheme of particle swarm
      optimizer is given to find the minimum for the energy in this paper. With this
      improved scheme, each pair of neighboring feature points along the boundaries of
      the desired objects are picked out from the set of sparse unorganized feature
      points, and the corresponding directional chord tangent angles are computed
      simultaneously to finish interpolation. We show experimentally and comparatively
      that the proposed method can perform effectively to restrict leakage on weak
      boundaries and premature convergence on long concave boundaries. Besides, it has
      good noise robustness and can as well extract multiple and open boundaries.

PMID- 19179256
TI  - [Endometriosis].
AB  - Endometriosis (ectopic endometrial tissue) is a benign condition with many
      symptoms (e.g., infertility dysmenorrhoea, pelvic pain) and may lead to serious
      complications. It affects women of reproductive age, however, in rare cases it
      may also develop before menarche. The estimated frequency of endometriosis used
      to be 1-2%, but since the advent of laparoscopy it has increased to 6-10%. Direct
      spread (e.g., in endometriosis interna seu adenomyosis), retrograde menstruation,
      embolisation, metaplasia together with defective immunological and genetic
      processes have all been confirmed as possible mechanisms of the development of
      disease. Laparoscopy plays a leading role in the diagnosis, however, physical
      examination and imaging techniques (e.g., sonography) remain an essential part of
      preoperative assessment. The treatments of endometriosis include various
      endocrine manipulations, surgery and palliation.

PMID- 19179257
TI  - [The intraarticular and local administration of glucocorticosteroid
      preparations].
AB  - The author reports the use of short-acting and combined short + long-acting
      betamethasone injections for intraarticular and local treatments. In this paper
      the author describes his experiences with intraarticular and local treatments of
      214 patients with 965 short-acting, and 416 patients with 2932 combined short +
      long-acting betamethasone preparations from 1978 to 2003. AIM: To describe the
      optimal application of intraarticular and local steroid therapy based on the
      author's experience and according to the literature data. METHOD: Patients were
      selected on the bases of rheumatological, laboratory and imaging investigations.
      The preparations were administered according to ARA guidelines. The results were
      evaluated based on patients' health status and symptoms, in addition to patients'
      and doctors' opinion. RESULTS: A combination of intraarticular short-acting +
      long-acting betamethasone injections resulted in patients being symptom-free
      (48.8%) or with significant improvement (37.5%), while local application led to a
      significant improvement (50%) or improvement (29%). Locally applied short-acting
      betamethasone resulted in symptom-free or significantly improved cases (40.6%),
      or ordinary improvement (40.3%). The short-acting + long-acting preparation was
      associated with mild side effects (62 cases), while the short-acting one had
      fewer mild side effects (10). The results are in agreement with the literature
      data, though in present author's case with a much fewer number of side effects.
      CONCLUSIONS: Intraarticular application of a combined short-acting + long acting
      agent is suggested exclusively in cases of visible and laboratory signs of
      inflammation that are limited to a few joints. In a treatment episode, not more
      than 3 injections may be permitted except in special cases. Initially,
      extraarticular management of cases is recommended using mainly short-acting
      preparations, except in protracted cases or when the application of short-acting
      steroids prove ineffective. Short-acting agents have little or short-term
      manifestations of corticosteroid toxicity. Taking such factors into
      consideration, treatment may be regarded as beneficial and safe. The aim of this
      publication is partly to influence practices in Hungarian surgeries.

PMID- 19179259
TI  - [Maximal initial dose of simvastatin causing acute renal failure through
      rhabdomyolysis: risk factors, pathomechanism and therapy related to a case].
AB  - Rhabdomyolysis (RML) is a rare and severe adverse effect of simvastatin (SIM).
      Several risk factors have been described which play a role in its pathogenesis,
      namely age >65, diabetes mellitus, renal disease, high-dose statin therapy,
      chemicals metabolized by cytochrome P450 3A4 or idiosyncrasy. CASE SUMMARY: A 66
      year-old man with diabetes, ischaemic heart disease and hypertension, on
      medication of CYP3A4 substrates amlodipine and alprazolam, maximal daily dose of
      SIM has been started for unknown cholesterol level. On the second day dark-brown
      urine, paraparesis, bile-like vomiting, on his fourth day of treatment total
      tetraparesis and oliguria characterized RML with acute renal failure. During his
      hospitalization of one-hundred-six days he underwent fourty-nine dialysis
      treatments. Sixteen months follow-up after discharge from hospital, his walking
      improved up to using one stick now. His cholesterol level is in physiological
      range with no statin therapy. CONCLUSIONS: On account of risk factors listed
      above this case should have been administered to low initial dose of SIM.
      Developing myalgia or weakness in muscles, treatment must be stopped. In a case
      of predisposition to RML statin therapy and dosage can only be performed under
      continuous supervision.

PMID- 19179258
TI  - [Statin therapy and muscle disorders].

PMID- 19179261
TI  - [Sucking and breastfeeding in practice and fine arts].

PMID- 19179260
TI  - [The principles of the treatment of pancreatic diabetes].
AB  - In pancreatic diabetes the whole of the Langerhans islets are damaged, which
      means that both the beta-cells and the alpha-cells are damaged. Unpredictable
      oscillations of blood glucose level are common due to malabsorption and
      maldigestion and one may count with explicit proneness to hypoglycaemia. The
      defence against hypoglycaemia also diminishes due to the damage of glucagon
      secretion, which is often aggravated by alcohol consumption. If normoglycaemia in
      pancreas diabetes cannot be achieved with appropriate diet, insulin treatment is
      necessary. Oral antidiabetic agents are not expedient. The best metabolic state
      can be achieved at the expense of the least amount of hypoglycaemia by giving the
      necessary minimum portions of insulin in an intensive, conservative insulin
      therapy. There is not enough experience with insulin analogs in pancreatic
      diabetes, but it seems expedient to use long-acting insulin analogs. The
      treatment of pancreas diabetes is a teamwork in which everybody has a decisive
      role, the gastroenterologist, the diabetologist, the dietitian and the diabetes
      nurse as well.

PMID- 19179263
TI  - [Interview with dr. Zoltan Toth, by B. Kirlay Gyorgyi].

PMID- 19179264
TI  - The Western Canada study: effective management of a high-profile study of risk.

PMID- 19179265
TI  - Association between exposure to emissions from the oil and gas industry and
      pathology of the immune, nervous, and respiratory systems, and skeletal and
      cardiac muscle in beef calves.
AB  - To determine potential associations between emissions from oil and gas field
      facilities and the risk of lesions in the immune, nervous, and respiratory
      systems of beef calves, researchers examined tissue samples collected from 1,531
      cases with exposure data, which included aborted fetuses, stillbirths, and calf
      mortalities from 203 cow-calf herds, by means of histopathology. The researchers
      prospectively measured exposure to sulfur dioxide, hydrogen sulfide, and volatile
      organic compounds by using air-monitoring data from passive monitors. They used
      the density of facilities surrounding each pasture as a second measure of
      exposure. Each tissue was classified by the presence or absence of a series of
      specified lesions, including those associated with degeneration, necrosis,
      infection, inflammation, anomaly, lympholysis (for lymphoid tissue), and
      proliferation (for the respiratory system). Exposure was not associated with the
      risk of lesions to tissues of either the immune or nervous system in calves that
      were aborted or died in spring 2002. Exposures to sulfur dioxide and hydrogen
      sulfide were not significantly associated with the risk of lesions to respiratory
      tissues in calves that were born alive in spring 2002. Increasing postnatal
      exposures to volatile organic compounds measured as benzene and toluene were
      associated with increased odds of respiratory lesions. The association between
      volatile organic compounds measured as benzene and respiratory lesions was
      significant for calves older than 3 weeks. During gestation, increasing exposure
      to sulfur dioxide was associated with increased odds of lesions in either the
      skeletal muscle or myocardium.

PMID- 19179266
TI  - Risk of abortion and stillbirth in cow-calf herds exposed to the oil and gas
      industry in Western Canada.
AB  - To investigate the associations between emissions from oil and gas field
      facilities and fetal survival, researchers followed more than 28,000 beef cows
      from the beginning of the breeding season through calving. They prospectively
      measured exposure to sulfur dioxide, hydrogen sulfide, and volatile organic
      compounds and linked them to the location of individual cattle; they used the
      density of oil and gas well sites surrounding each pasture as an alternate
      measure of exposure. The researchers measured the risks of abortion and
      stillbirth in 203 cow-calf herds for the 2002 calving season, as well as animal
      and herd-management factors known or suspected to affect these parameters. Using
      mixed models to adjust for clustering by herd and after accounting for other
      known risk factors, they examined the associations between exposure to sulfur
      dioxide, volatile organic compounds measured as benzene and toluene, hydrogen
      sulfide, and well-site density, and the risks of abortion and stillbirth. There
      was no evidence across the measured range of exposures that emissions of sulfur
      dioxide, hydrogen sulfide, volatile organic compounds measured as benzene or
      toluene, or well-site density increased the risk of either abortion or stillbirth
      in these beef herds.

PMID- 19179267
TI  - Associations between immune function in yearling beef cattle and airborne
      polycyclic aromatic hydrocarbons and PM1.0 near oil and natural gas field
      facilities.
AB  - Researchers determined the potential associations between exposure to airborne
      fine particulate matter (ie, particulate matter that is < 1 microm in diameter,
      or PM1.0) and polycyclic aromatic hydrocarbons (PAHs) and immune system function
      in beef cattle by using blood samples collected from yearling cattle in 22 herds
      in the spring of 2002. The herds were located at variable distances from industry
      field facilities in the major oil- and gas-producing areas of western Canada. The
      researchers evaluated immune system competence by measuring populations of B
      lymphocytes and T-lymphocyte subtypes (CD4, CD8, gammadelta, and WC1) in
      peripheral circulation (n = 469), and systemic antibody production in response to
      vaccine administration (n = 446). They used particulate air monitors to estimate
      the exposure of the cattle to airborne contaminants by determining mean monthly
      concentrations of PM1.0 and 24 different PAHs from January to June. The mean
      concentration of PAHs measured in the ambient air of herds monitored in this
      study was low, with naphthalene being present in the highest concentration
      (geometric mean = 5.6 ng/m3; geometric standard deviation = 38), followed by 1
      methylnaphthalene (geometric mean = 2.2 ng/m3; geometric standard deviation =
      12). The geometric mean monthly exposure to PM1.0 was 7.1 microg/m3 (geometric
      standard deviation = 1.5) for the same period. The researchers detected no
      significant plausible associations between exposure to any measured airborne
      contaminants and immune system function.

PMID- 19179268
TI  - Associations between in utero exposure to airborne emissions from oil and gas
      production and processing facilities and immune system outcomes in neonatal beef
      calves.
AB  - To determine if oil- and gas-facility emissions prospectively measured as
      airborne sulfur dioxide and volatile organic compounds (VOCs) were associated
      with immunomodulation in neonatal beef calves, veterinarians collected samples
      from 325 calves from 60 western Canadian herds in the spring of 2002. Researchers
      assessed immune system effects by enumerating B-lymphocytes and specific T
      lymphocyte subtypes (CD4, CD8, gammadelta, and WC1) in peripheral circulation
      using flow cytometry. They estimated in utero exposure for each calf from the
      earliest possible breeding date of the dam to the calving date, using air-quality
      data from passive monitors installed in pastures and wintering areas. Numbers of
      circulating CD4 and CD8 T-lymphocytes were 42% and 43% lower, respectively, in
      calves exposed to the highest quartile (> or = 0.378 microg/m3) of VOCs measured
      as airborne concentrations of benzene compared with calves exposed to
      concentrations in the lowest quartile (< 0.276 microg/m3). Similarly, the number
      of CD4 T-lymphocytes was 40% lower in calves exposed to VOCs measured as
      concentrations of toluene in the highest quartile (> or = 0.713 microg/m3),
      compared with calves exposed to concentrations in the lowest quartile (< 0.348
      microg/m3). There was no statistically significant association between in utero
      exposure and numbers of B-lymphocytes and gammadelta and WC1 T-lymphocyte
      subtypes in calf blood samples.

PMID- 19179269
TI  - Associations between immune function in yearling beef cattle and airborne
      emissions of sulfur dioxide, hydrogen sulfide, and VOCs from oil and natural gas
      facilities.
AB  - Researchers assessed the associations between airborne emissions from oil and gas
      field facilities and the structure and function of the immune system of yearling
      beef cattle in 27 herds during spring 2002. They evaluated the immune systems of
      these animals by enumerating B lymphocytes and T-lymphocyte subtypes (CD4, CD8,
      gammadelta, and WC1) in peripheral circulation and by measuring systemic antibody
      production in response to vaccination. Researchers prospectively measured
      exposure to sulfur dioxide, hydrogen sulfide, and volatile organic compounds
      (VOCs) by using air-quality data from passive monitors installed in pastures and
      wintering areas. They estimated the mean exposure of each animal over the 6-month
      period before the start of sample collection. The researchers used mixed models,
      which adjusted for clustering by herd and accounted for known risk factors, to
      examine potential associations between exposure to airborne sulfur dioxide, VOCs
      (measured as concentrations of benzene and toluene) and hydrogen sulfide, as well
      as proximity to emission sources (well-site density), and the immune system
      outcomes. Increasing exposure to VOCs measured as toluene was associated with
      significant CD4 T lymphocytopenia. The number of CD4 T lymphocytes was 30% lower
      in cattle exposed to VOCs measured as toluene in the highest quartile (> 0.823
      microg/m3) than in cattle exposed in the lowest quartile (< 0.406 microg/m3).

PMID- 19179270
TI  - Seasonal and sex variation of high-sensitivity C-reactive protein in healthy
      adults: a longitudinal study.
AB  - BACKGROUND: Cross-sectional studies have reported seasonal variation in high
      sensitivity C-reactive protein (hsCRP). However, longitudinal data are lacking.
      METHODS: We collected data on diet, physical activity, psychosocial factors,
      physiology, and anthropometric measurements from 534 healthy adults (mean age 48
      years, 48.5% women, 87% white) at quarterly intervals over a 1-year period
      between 1994 and 1998. Using sinusoidal regression models, we estimated peak-to
      trough amplitude and phase of the peaks. RESULTS: At baseline, average hsCRP was
      1.72 mg/L (men, 1.75 mg/L; women, 1.68 mg/L). Overall seasonal variation
      amplitude was 0.16 mg/L (95% CI 0.02 to 0.30) and was lower in men (0.10 mg/L,
      95% CI -0.11 to 0.31) than in women (0.23 mg/L, 95% CI 0.04 to 0.42). In both
      sexes, hsCRP peaked in November, with a corresponding trough in May. Relative
      plasma volume, waist and hip circumference, diastolic blood pressure, and
      depression scores were major factors associated with changes in amplitude of
      seasonal variation of hsCRP, and taken together explain most of the observed
      seasonal change. There was a 20% increase in the percentage of participants
      classified in the high-risk category for hsCRP (> or =3 mg/L) during late fall
      and early winter compared with late spring and early summer. CONCLUSIONS:
      Concentrations of hsCRP were modestly increased in fall and winter compared to
      summer, with greater seasonal amplitude of variation observed in women.
      Conventional classification methods fail to consider seasonality in hsCRP and may
      result in substantial misclassifications in the spring and fall. Future clinical
      practice and research should take these variations into account.

PMID- 19179271
TI  - Different apparent prognostic value of hsCRP in type 2 diabetic and nondiabetic
      patients with acute coronary syndromes.
AB  - BACKGROUND: C-reactive protein (CRP) is an established prognostic marker in acute
      coronary syndromes (ACS); however, no study has specifically addressed its
      prognostic role in type 2 diabetes with ACS. We evaluated the prognostic role of
      CRP separately in diabetic and nondiabetic patients with ACS. METHODS: We
      enrolled 251 patients with unstable angina and measured serum concentrations of
      high sensitivity (hs)CRP. Ninety-seven patients underwent coronary angiography
      with evaluation of atherosclerotic disease severity and extent by Bogaty score.
      Assessed endpoint was the combined occurrence of myocardial infarction (MI) and
      death at 1 year. RESULTS: No significant differences were found in hs-CRP between
      patients with and without diabetes. By Cox regression, hsCRP was not associated
      with 1-year follow-up events in diabetic patients but was strongly associated
      with events in nondiabetic patients (P = 0.0012). Coronary angiography exhibited
      a higher extent index in patients with diabetes than in those without (P = 0.04).
      hsCRP concentrations were not associated with angiographic atherosclerotic
      burden. By Cox analysis, hsCRP and extent score were associated with events in
      patients who underwent coronary angiography (P < 0.001 and P = 0.034,
      respectively). In nondiabetic patients, hsCRP was the only predictor of events at
      1-year follow-up (P < 0.001), whereas in diabetic patients, hsCRP was not
      associated with events and a weak association was observed for extent score (P =
      0.06). CONCLUSIONS: Our study suggests that different pathophysiological
      mechanisms may be responsible for MI and death in unstable angina patients with
      or without diabetes and that severity of coronary artery disease plays a major
      role in diabetes (and inflammation in the absence of diabetes).

PMID- 19179272
TI  - Myocardial infarction in a 72-year-old woman with low LDL-C and increased hsCRP:
      implications for statin therapy.

PMID- 19179277
TI  - Interdisciplinary research for managing ecosystem services.

PMID- 19179278
TI  - An anterior temporal face patch in human cortex, predicted by macaque maps.
AB  - Increasing evidence suggests that primate visual cortex has a specialized
      architecture for processing discrete object categories such as faces. Human fMRI
      studies have described a localized region in the fusiform gyrus [the fusiform
      face area (FFA)] that responds selectively to faces. In contrast, in nonhuman
      primates, electrophysiological and fMRI studies have instead revealed 2
      apparently analogous regions of face representation: the posterior temporal face
      patch (PTFP) and the anterior temporal face patch (ATFP). An earlier study
      suggested that human FFA is homologous to the PTFP in macaque. However, in
      humans, no obvious homologue of the macaque ATFP has been demonstrated. Here, we
      used fMRI to map face-selective sites in both humans and macaques, based on
      equivalent stimuli in a quantitative topographic comparison. This fMRI evidence
      suggests that such a face-selective area exists in human anterior inferotemporal
      cortex, comprising the apparent homologue of the fMRI-defined ATFP in macaques.

PMID- 19179279
TI  - Beta1 integrins differentially control extravasation of inflammatory cell subsets
      into the CNS during autoimmunity.
AB  - Inhibiting the alpha(4) subunit of the integrin heterodimers alpha(4)beta(1) and
      alpha(4)beta(7) with the monoclonal antibody natalizumab is an effective
      treatment for multiple sclerosis (MS). However, the pharmacological action of
      natalizumab is not understood conclusively. Previous studies suggested that
      natalizumab inhibits activation, proliferation, or extravasation of inflammatory
      cells. To specify which mechanisms, cell types, and alpha(4) heterodimers are
      affected by the antibody treatment, we studied MS-like experimental autoimmune
      encephalomyelitis (EAE) in mice lacking the beta(1)-integrin gene either in all
      hematopoietic cells or selectively in T lymphocytes. Our results show that T
      cells critically rely on beta(1) integrins to accumulate in the central nervous
      system (CNS) during EAE, whereas CNS infiltration of beta(1)-deficient myeloid
      cells remains unaffected, suggesting that T cells are the main target of anti
      alpha(4)-antibody blockade. We demonstrate that beta(1)-integrin expression on
      encephalitogenic T cells is critical for EAE development, and we therefore
      exclude alpha(4)beta(7) as a target integrin of the antibody treatment. T cells
      lacking beta(1) integrin are unable to firmly adhere to CNS endothelium in vivo,
      whereas their priming and expansion remain unaffected. Collectively, these
      results suggest that the primary action of natalizumab is interference with T
      cell extravasation via inhibition of alpha(4)beta(1) integrins.

PMID- 19179280
TI  - Science for managing ecosystem services: Beyond the Millennium Ecosystem
      Assessment.
AB  - The Millennium Ecosystem Assessment (MA) introduced a new framework for analyzing
      social-ecological systems that has had wide influence in the policy and
      scientific communities. Studies after the MA are taking up new challenges in the
      basic science needed to assess, project, and manage flows of ecosystem services
      and effects on human well-being. Yet, our ability to draw general conclusions
      remains limited by focus on discipline-bound sectors of the full social
      ecological system. At the same time, some polices and practices intended to
      improve ecosystem services and human well-being are based on untested assumptions
      and sparse information. The people who are affected and those who provide
      resources are increasingly asking for evidence that interventions improve
      ecosystem services and human well-being. New research is needed that considers
      the full ensemble of processes and feedbacks, for a range of biophysical and
      social systems, to better understand and manage the dynamics of the relationship
      between humans and the ecosystems on which they rely. Such research will expand
      the capacity to address fundamental questions about complex social-ecological
      systems while evaluating assumptions of policies and practices intended to
      advance human well-being through improved ecosystem services.

PMID- 19179281
TI  - Irreversible climate change due to carbon dioxide emissions.
AB  - The severity of damaging human-induced climate change depends not only on the
      magnitude of the change but also on the potential for irreversibility. This paper
      shows that the climate change that takes place due to increases in carbon dioxide
      concentration is largely irreversible for 1,000 years after emissions stop.
      Following cessation of emissions, removal of atmospheric carbon dioxide decreases
      radiative forcing, but is largely compensated by slower loss of heat to the
      ocean, so that atmospheric temperatures do not drop significantly for at least
      1,000 years. Among illustrative irreversible impacts that should be expected if
      atmospheric carbon dioxide concentrations increase from current levels near 385
      parts per million by volume (ppmv) to a peak of 450-600 ppmv over the coming
      century are irreversible dry-season rainfall reductions in several regions
      comparable to those of the "dust bowl" era and inexorable sea level rise. Thermal
      expansion of the warming ocean provides a conservative lower limit to
      irreversible global average sea level rise of at least 0.4-1.0 m if 21st century
      CO(2) concentrations exceed 600 ppmv and 0.6-1.9 m for peak CO(2) concentrations
      exceeding approximately 1,000 ppmv. Additional contributions from glaciers and
      ice sheet contributions to future sea level rise are uncertain but may equal or
      exceed several meters over the next millennium or longer.

PMID- 19179282
TI  - Stem cell fate dictated solely by altered nanotube dimension.
AB  - Two important goals in stem cell research are to control the cell proliferation
      without differentiation and to direct the differentiation into a specific cell
      lineage when desired. Here, we demonstrate such paths by controlling only the
      nanotopography of culture substrates. Altering the dimensions of nanotubular
      shaped titanium oxide surface structures independently allowed either augmented
      human mesenchymal stem cell (hMSC) adhesion or a specific differentiation of
      hMSCs into osteoblasts by using only the geometric cues, absent of osteogenic
      inducing media. hMSC behavior in response to defined nanotube sizes revealed a
      very dramatic change in hMSC behavior in a relatively narrow range of nanotube
      dimensions. Small (approximately 30-nm diameter) nanotubes promoted adhesion
      without noticeable differentiation, whereas larger (approximately 70- to 100-nm
      diameter) nanotubes elicited a dramatic stem cell elongation (approximately 10
      fold increased), which induced cytoskeletal stress and selective differentiation
      into osteoblast-like cells, offering a promising nanotechnology-based route for
      unique orthopedics-related hMSC treatments.

PMID- 19179283
TI  - Functional coding variation in recombinant inbred mouse lines reveals multiple
      serotonin transporter-associated phenotypes.
AB  - The human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT, SLC6A4)
      figures prominently in the etiology and treatment of many prevalent
      neurobehavioral disorders including anxiety, alcoholism, depression, autism, and
      obsessive-compulsive disorder (OCD). Here, we use naturally occurring
      polymorphisms in recombinant inbred (RI) lines to identify multiple phenotypes
      associated with altered SERT function. The widely used mouse strain C57BL/6J,
      harbors a SERT haplotype defined by 2 nonsynonymous coding variants [Gly-39 and
      Lys-152 (GK)]. At these positions, many other mouse lines, including DBA/2J,
      encode, respectively, Glu-39 and Arg-152 (ER haplotype), amino acids found also
      in hSERT. Ex vivo synaptosomal 5-HT transport studies revealed reduced uptake
      associated with the GK variant, a finding confirmed by in vitro heterologous
      expression studies. Experimental and in silico approaches using RI lines
      (C57BL/6J x DBA/2J = BXD) identify multiple anatomical, biochemical, and
      behavioral phenotypes specifically impacted by GK/ER variation. Among our
      findings are several traits associated with alcohol consumption and multiple
      traits associated with dopamine signaling. Further bioinformatic analysis of BXD
      phenotypes, combined with biochemical evaluation of SERT knockout mice, nominates
      SERT-dependent 5-HT signaling as a major determinant of midbrain iron homeostasis
      that, in turn, dictates iron-regulated DA phenotypes. Our studies provide an
      example of the power of coordinated in vitro, in vivo, and in silico approaches
      using mouse RI lines to elucidate and quantify the system-level impact of gene
      variation.

PMID- 19179284
TI  - Quantitative peptidomics reveal brain peptide signatures of behavior.
AB  - The honey bee genome predicts approximately 100 peptides from 36 prohormones, but
      the functions of many of these peptides are unknown. We used differential isotope
      labeling combined with mass spectrometric analysis to quantify approximately 50%
      of known bee brain peptides in the context of foraging, with 8 showing robust and
      dynamic regulation. Some showed differences in brain abundance as a function of
      experience; specifically, nectar and pollen collection led to quick changes in
      abundance. These changes were related to the act of food collection, not
      ingestion, because foragers bring food back to the hive for storage rather than
      eating it themselves. Other peptide differences in brain abundance were seen in
      bees that either flew to a nectar feeder or a pollen feeder, but did not yet
      collect any food. These differences likely reflect well-known predispositions of
      some bees to collect either nectar or pollen, but not both. Tachykinin, PBAN, and
      sNPF were among the peptides with the strongest changes in association with
      nectar and pollen foraging. These peptides are known to be involved in regulating
      food intake in solitary insects, suggesting an evolutionary connection between
      that behavior and social foraging. These results demonstrate that it is now
      possible to use quantitative peptidomics to help determine which brain peptides
      are bioactive and to elucidate their function in the regulation of behavior.

PMID- 19179285
TI  - Mammalian metallopeptidase inhibition at the defense barrier of Ascaris parasite.
AB  - Roundworms of the genus Ascaris are common parasites of the human
      gastrointestinal tract. A battery of selective inhibitors protects them from host
      enzymes and the immune system. Here, a metallocarboxypeptidase (MCP) inhibitor,
      ACI, was identified in protein extracts from Ascaris by intensity-fading MALDI
      TOF mass spectrometry. The 67-residue amino acid sequence of ACI showed no
      significant homology with any known protein. Heterologous overexpression and
      purification of ACI rendered a functional molecule with nanomolar equilibrium
      dissociation constants against MCPs, which denoted a preference for digestive and
      mast cell A/B-type MCPs. Western blotting and immunohistochemistry located ACI in
      the body wall, intestine, female reproductive tract, and fertilized eggs of
      Ascaris, in accordance with its target specificity. The crystal structure of the
      complex of ACI with human carboxypeptidase A1, one of its potential targets in
      vivo, revealed a protein with a fold consisting of two tandem homologous domains,
      each containing a beta-ribbon and two disulfide bonds. These domains are
      connected by an alpha-helical segment and a fifth disulfide bond. Binding and
      inhibition are exerted by the C-terminal tail, which enters the funnel-like
      active-site cavity of the enzyme and approaches the catalytic zinc ion. The
      findings reported provide a basis for the biological function of ACI, which may
      be essential for parasitic survival during infection.

PMID- 19179286
TI  - Polymorphisms in CD1d affect antigen presentation and the activation of CD1d
      restricted T cells.
AB  - CD1 proteins constitute a distinct lineage of antigen-presenting molecules
      specialized for the presentation of lipid antigens to T cells. In contrast to the
      extensive sequence polymorphism characteristic of classical MHC molecules, CD1
      proteins exhibit limited sequence diversity. Here, we describe the identification
      and characterization of CD1d alleles in wild-derived mouse strains. We
      demonstrate that polymorphisms in CD1d affect the presentation of endogenous and
      exogenous ligands to CD1d-restricted T cells, including type I (Valpha14i) and
      type II (non-Valpha14i) natural killer T (NKT) cells. Using congenic mice, we
      found CD1d polymorphisms affect the thymic selection of type I NKT cells and
      induce allogeneic T cell responses. Collectively, results from these studies
      demonstrate a role for polymorphisms in influencing the development and function
      of CD1d-restricted T cells.

PMID- 19179288
TI  - Interference in acetylene intersystem crossing acts as the molecular analog of
      Young's double-slit experiment.
AB  - We report on an experimental approach that reveals crucial details of the
      composition of singlet-triplet mixed eigenstates in acetylene. Intersystem
      crossing in this prototypical polyatomic molecule embodies the mixing of the
      lowest excited singlet state (S(1)) with 3 triplet states (T(1), T(2), and T(3)).
      Using high-energy (157-nm) photons from an F(2) laser to record excited-state
      photoelectron spectra, we have decomposed the mixed eigenstates into their S(1),
      T(3), T(2), and T(1) constituent parts. One example of the interpretive power
      that ensues from the selective sensitivity of the experiment to the individual
      electronic state characters is the discovery and examination of destructive
      interference between two doorway-mediated intersystem crossing pathways. This
      observation of an interference effect in nonradiative decay opens up
      possibilities for rational coherent control over molecular excited state
      dynamics.

PMID- 19179287
TI  - The substrate-binding protein imposes directionality on an electrochemical sodium
      gradient-driven TRAP transporter.
AB  - Substrate-binding protein-dependent secondary transporters are widespread in
      prokaryotes and are represented most frequently by members of the tripartite ATP
      independent periplasmic (TRAP) transporter family. Here, we report the membrane
      reconstitution of a TRAP transporter, the sialic acid-specific SiaPQM system from
      Haemophilus influenzae, and elucidate its mechanism of energy coupling. Uptake of
      sialic acid via membrane-reconstituted SiaQM depends on the presence of the
      sialic acid-binding protein, SiaP, and is driven by the electrochemical sodium
      gradient. The interaction between SiaP and SiaQM is specific as transport is not
      reconstituted using the orthologous sialic acid-binding protein VC1779.
      Importantly, the binding protein also confers directionality on the transporter,
      and reversal of sialic acid transport from import to export is only possible in
      the presence of an excess of unliganded SiaP.

PMID- 19179289
TI  - Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola
      glycoprotein.
AB  - Mammalian cells employ numerous innate cellular mechanisms to inhibit viral
      replication and spread. Tetherin, also known as Bst-2 or CD317, is a recently
      identified, IFN-induced, cellular response factor that blocks release of HIV-1
      and other retroviruses from infected cells. The means by which tetherin retains
      retroviruses on the cell surface, as well as the mechanism used by the HIV-1
      accessory protein Vpu to antagonize tetherin function and promote HIV-1 release,
      are unknown. Here, we document that tetherin functions as a broadly acting
      antiviral factor by demonstrating that both human and murine tetherin potently
      inhibit the release of the filovirus, Ebola, from the surface of cells.
      Expression of the Ebola glycoprotein (GP) antagonized the antiviral effect of
      human and murine tetherin and facilitated budding of Ebola particles, as did the
      HIV-1 Vpu protein. Conversely, Ebola GP could substitute for Vpu to promote HIV-1
      virion release from tetherin-expressing cells, demonstrating a common cellular
      target for these divergent viral proteins. Ebola GP efficiently
      coimmunoprecipitated with tetherin, suggesting that the viral glycoprotein
      directly interferes with this host antiviral factor. These results demonstrate
      that tetherin is a cellular antiviral factor that restricts budding of
      structurally diverse enveloped viruses. Additionally, Ebola has evolved a highly
      effective strategy to combat this antiviral response elicited in the host during
      infection.

PMID- 19179290
TI  - The delta isoform of CaM kinase II is required for pathological cardiac
      hypertrophy and remodeling after pressure overload.
AB  - Acute and chronic injuries to the heart result in perturbation of intracellular
      calcium signaling, which leads to pathological cardiac hypertrophy and
      remodeling. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been
      implicated in the transduction of calcium signals in the heart, but the specific
      isoforms of CaMKII that mediate pathological cardiac signaling have not been
      fully defined. To investigate the potential involvement in heart disease of
      CaMKIIdelta, the major CaMKII isoform expressed in the heart, we generated
      CaMKIIdelta-null mice. These mice are viable and display no overt abnormalities
      in cardiac structure or function in the absence of stress. However, pathological
      cardiac hypertrophy and remodeling are attenuated in response to pressure
      overload in these animals. Cardiac extracts from CaMKIIdelta-null mice showed
      diminished kinase activity toward histone deacetylase 4 (HDAC4), a substrate of
      stress-responsive protein kinases and suppressor of stress-dependent cardiac
      remodeling. In contrast, phosphorylation of the closely related HDAC5 was
      unaffected in hearts of CaMKIIdelta-null mice, underscoring the specificity of
      the CaMKIIdelta signaling pathway for HDAC4 phosphorylation. We conclude that
      CaMKIIdelta functions as an important transducer of stress stimuli involved in
      pathological cardiac remodeling in vivo, which is mediated, at least in part, by
      the phosphorylation of HDAC4. These findings point to CaMKIIdelta as a potential
      therapeutic target for the maintenance of cardiac function in the setting of
      pressure overload.

PMID- 19179291
TI  - Tbx2b is required for ultraviolet photoreceptor cell specification during
      zebrafish retinal development.
AB  - The vertebrate rod and cone photoreceptors are highly specialized sensory neurons
      that transduce light into the chemical and electrical signals of the nervous
      system. Although the physiological properties of cones and rods are well known,
      only a handful of genes have been identified that regulate the specification of
      photoreceptor subtypes. Taking advantage of the mosaic organization of
      photoreceptors in zebrafish, we report the isolation of a mutation resulting in a
      unique change in photoreceptor cell fate. Mutation of the lots-of-rods (lor)
      locus results in a near one-for-one transformation of UV-cone precursors into
      rods. The transformed cells exhibit morphological characteristics and a gene
      expression pattern typical of rods, but differentiate in a temporal and spatial
      pattern consistent with UV-cone development. In mutant larvae and adults, the
      highly ordered photoreceptor mosaic is maintained and degeneration is not
      observed, suggesting that lor functions after the specification of the other
      photoreceptor subtypes. In genetic chimeras, lor functions cell-autonomously in
      the specification of photoreceptor cell fate. Linkage analysis and genetic
      complementation testing indicate that lor is an allele of tbx2b/fby (from
      beyond). fby was identified by a pineal complex phenotype, and carries a nonsense
      mutation in the T-box domain of the tbx2b transcription factor. Homozygous fby
      mutant larvae and lor/fby transheterozygotes also display the lots-of-rods
      phenotype. Based upon these data, we propose a previously undescribed function
      for tbx2b in photoreceptor cell precursors, to promote the UV cone fate by
      repressing the rod differentiation pathway.

PMID- 19179293
TI  - A regulatory science perspective on warfarin therapy: a pharmacogenetic
      opportunity.
AB  - Warfarin is a challenging drug to accurately dose, both initially and for
      maintenance, because of its narrow therapeutic range, wide interpatient
      variability, and long list of factors that can influence dosing. Two million
      people in the United States are initiated on warfarin therapy annually, and this
      number is steadily increasing because of the increase in number of eligible
      patients. Recently, warfarin was reported to be the fourth leading cause of
      adverse events. The U.S. Food and Drug Administration recognizes that the adverse
      event rate of warfarin can be improved through better initial dosing, because
      many of the serious adverse events of warfarin occur soon after starting
      treatment. A substantial number of studies demonstrate that common variants of
      two genes, VKORC1 and CYP2C9, along with other nongenetic factors, correlate
      significantly with warfarin dosing. The genotypes of VKORC1 and CYP2C9 alone
      account for nearly 3 times more of the variability ( approximately 30%) in
      warfarin dosing than do age, weight, gender, and other clinical factors combined
      ( approximately 12%). Therefore, the purpose of this report is to review the
      current recommendations for warfarin therapy that involve genetic testing.

PMID- 19179292
TI  - PGC-1alpha is coupled to HIF-1alpha-dependent gene expression by increasing
      mitochondrial oxygen consumption in skeletal muscle cells.
AB  - Mitochondrial biogenesis occurs in response to increased cellular ATP demand. The
      mitochondrial electron transport chain requires molecular oxygen to produce ATP.
      Thus, increased ATP generation after mitochondrial biogenesis results in
      increased oxygen demand that must be matched by a corresponding increase in
      oxygen supply. We found that overexpression of peroxisome proliferator-activated
      receptor-gamma coactivator 1alpha (PGC-1alpha), which increases mitochondrial
      biogenesis in primary skeletal muscle cells, leads to increased expression of a
      cohort of genes known to be regulated by the dimeric hypoxia-inducible factor
      (HIF), a master regulator of the adaptive response to hypoxia. PGC-1alpha
      dependent induction of HIF target genes under physiologic oxygen concentrations
      is not through transcriptional coactivation of HIF or up-regulation of HIF-1alpha
      mRNA but through HIF-1alpha protein stabilization. It occurs because of
      intracellular hypoxia as a result of increased oxygen consumption after
      mitochondrial biogenesis. Thus, we propose that at physiologic oxygen
      concentrations, PGC-1alpha is coupled to HIF signaling through the regulation of
      intracellular oxygen availability, allowing cells and tissues to match increased
      oxygen demand after mitochondrial biogenesis with increased oxygen supply.

PMID- 19179294
TI  - Lopinavir/ritonavir pharmacokinetics in a substitution of high-dose soft-gelatin
      capsule to tablet formulation.
AB  - Guidelines recommend that when soft-gelatin capsules of lopinavir/ritonavir are
      co-administered with CYP3A4-inducing agents, doses should be increased to 4
      capsules (533 mg/133 mg) twice daily. No evidence is available to guide dosing of
      lopinavir/ritonavir in tablet formulation in this setting. A single-center study
      is conducted to compare the pharmacokinetics of high-dose lopinavir/ritonavir in
      34 patients on stable HAART regimens including 4 soft-gelatin capsules twice
      daily who then switch to 3 tablets (600 mg/150 mg) twice daily. Median C(min) on
      soft-gelatin capsule and tablets is 4700 ng/mL (interquartile range [IQR] 2310,
      6000 ng/mL) and 5640 ng/mL (IQR 4290, 8080 ng/mL), respectively, for those on
      inducing agents (n = 17). For patients not on inducing agents (n = 17), median
      C(min) on soft-gelatin capsule and tablets is 5170 ng/mL (IQR 3640, 6210 ng/mL)
      and 5640 ng/mL (IQR 4290, 8080 ng/mL), respectively. Among treatment-experienced
      patients on lopinavir/ritonavir capsules 533/133 mg twice daily, a switch to
      tablets 600/150 mg twice daily produces comparable pharmacokinetics, regardless
      of whether they receive concomitant CYP3A4-inducing antiretroviral agents.

PMID- 19179295
TI  - Population pharmacokinetic modeling of ustekinumab, a human monoclonal antibody
      targeting IL-12/23p40, in patients with moderate to severe plaque psoriasis.
AB  - The population pharmacokinetics of ustekinumab are characterized in patients with
      moderate to severe plaque psoriasis in 2 Phase 3 studies (PHOENIX 1 and PHOENIX
      2). Serum concentration data from 1937 patients are analyzed to determine
      pharmacokinetic characteristics of ustekinumab and to assess factors that may
      contribute to their variability. The population typical mean (percentage relative
      standard error) values for apparent clearance, apparent volume of distribution,
      and absorption rate constant from the final covariate model are 0.465 L.day(-1)
      (2.0%), 15.7 L (2.0%), and 0.354 day(-1) (16.2%), respectively. The
      interindividual variabilities for apparent clearance and apparent volume of
      distribution are 41.0% and 33.2%, respectively. Of the factors evaluated in this
      analysis, body weight, diabetes, and positive immune response (antibodies to
      ustekinumab) are important covariates affecting the apparent clearance and/or
      apparent volume of distribution of ustekinumab. To fully understand the clinical
      relevance of these results, the covariate findings need to be evaluated
      concurrently with the efficacy and safety data.

PMID- 19179297
TI  - Population pharmacokinetics of mycophenolic acid and its 2 glucuronidated
      metabolites in kidney transplant recipients.
AB  - The population pharmacokinetics of mycophenolic acid (MPA) and its phenolic
      (MPAG) and acyl (AcMPAG) glucuronide metabolites were studied in patients taking
      enteric-coated mycophenolate sodium. Plasma samples (n = 232), obtained from 18
      renal transplant recipients, were analyzed for MPA, MPAG, and AcMPAG using a
      validated high-performance liquid chromatography/ultraviolet assay. Population
      pharmacokinetic analysis was performed using NONMEM. The pharmacokinetics of MPA
      were best described by a 2-compartment model, with MPAG and AcMPAG produced from
      the central compartment and with enterohepatic recirculation of MPA via these 2
      metabolites. Population mean estimates for MPA were apparent clearance (CL/F) of
      10.6 L/h (interindividual variability [IIV] = 21.4%) and apparent volume of
      distribution of the central compartment (V(1)/F) of 25.9 L (IIV = 87.8%). Mean
      elimination rate constants of MPAG and AcMPAG were 0.323 h(-1) (IIV = 29.1%) and
      0.206 h(-1) (IIV = 48.8%), respectively. The mean fraction of MPA converted to
      MPAG and AcMPAG, normalized by their volumes of distribution (FM(AG) and FM(AC),
      respectively), was also estimated. The elimination rate constant for MPAG and
      FM(AC) was influenced by glomerular filtration rate in patients with renal
      impairment. The visual predictive check, based on 100 simulated data sets each
      for MPA, MPAG, and AcMPAG, found that the final pharmacokinetic model adequately
      predicts the observed concentrations of all 3 species.

PMID- 19179296
TI  - The effect of reporting methods for dosing times on the estimation of
      pharmacokinetic parameters of escitalopram.
AB  - The objective of this study was to compare population pharmacokinetic models of
      escitalopram developed from dosage times recorded by a medication event
      monitoring system (MEMS) versus the reported times from patients with diagnosed
      depression. Seventy-three patients were prescribed doses of 10, 15, or 20 mg
      escitalopram daily. Sparse blood samples were collected at weeks 4, 12, 24, and
      36 with 185 blood samples obtained from the 73 patients. NONMEM was used to
      develop a population pharmacokinetic model based on dosing records obtained from
      MEMS prior to each blood sample time. A separate population pharmacokinetic
      analysis using NONMEM was performed for the same population using the patient
      reported last dosing time and assuming a steady-state condition as the model
      input. Objective function values and goodness-of-fit plots were used as model
      selection criteria. The absolute mean difference in the last dosing time between
      MEMS and patient-reported times was 4.48 +/- 10.12 hours. A 1-compartment model
      with first-order absorption and elimination was sufficient for describing the
      data. Estimated oral clearance (CL/F) to escitalopram was statistically
      insensitive to reported dosing methods (MEMS vs patient reported: 25.5 [7.0%] vs
      26.9 [6.6%] L/h). However, different dosing report methods resulted in
      significantly different estimates on the volume of distribution (V/F; MEMS vs
      patient reported: 1000 [17.3%] vs 767 [17.5%] L) and the absorption rate constant
      K(a) (MEMS vs patient reported: 0.74 [45.7%] vs 0.51 [35.4%] h(-1)) for
      escitalopram. Furthermore, the parameters estimated from the MEMS method were
      similar to literature reported values for V/F ( approximately 1100 L) and K(a) (
      approximately 0.8-0.9 h(-1)) arising from traditional pharmacokinetic approaches.

PMID- 19179298
TI  - A pharmacokinetic and pharmacodynamic comparison of synthetic and recombinant
      oral salmon calcitonin.
AB  - The aim of this study was to assess the bioavailability and pharmacodynamic
      efficacy of synthetic salmon calcitonin (ssCT) and recombinant salmon calcitonin
      (rsCT) in healthy postmenopausal women. The study was a single-blind, randomized
      study. Participants were 36 postmenopausal women 62 to 74 years old, randomly
      assigned to a comparison of dosing with ssCT (n = 12) or rsCT (n = 24) given in
      the morning at 08:00. Study parameters were plasma CT levels measured up to 2
      hours postdose and changes in the bone resorption marker serum CTX-I and the
      cartilage degradation marker urine CTX-II measured up to 4 hours postdose. For
      both formulations, peak plasma concentrations were obtained 15 minutes after
      dosage, and no statistically significant differences in the uptake of CT were
      observed. Measurement of bone resorption and cartilage degradation markers
      displayed comparable responses, with AUCs of relative change of serum CTX-I of 
      250% x hours and relative change of urine CTX-II of -180% x hours during the 4
      hour observation period. In conclusion, oral synthetic and recombinant calcitonin
      displayed comparable pharmacodynamic and kinetic properties.

PMID- 19179299
TI  - Pharmacokinetics of valsartan in pediatric and adolescent subjects with
      hypertension.
AB  - An open-label, single-dose study is conducted in 26 children with hypertension to
      characterize the pharmacokinetics of valsartan. Valsartan is administered as an
      oral suspension (dose of 2 mg/kg), with the maximum single dose being 80 mg.
      Subjects are stratified into 4 age categories: group 1, 1 to less than 4 years;
      group 2, 4 to less than 6 years; group 3, 6 to less than 12 years; group 4, 12 to
      16 years. Blood samples are collected before and for 24 hours after dosing to
      quantitate valsartan. Because the body weight of most children in groups 3 and 4
      exceeds 40 kg and they received a dose of less than 2 mg/kg, major
      pharmacokinetic parameters are dose normalized for comparison across the age
      groups. Dose-normalized maximum plasma concentration and area under the plasma
      concentration curve and body weight-normalized apparent oral clearance are
      comparable for the 4 groups (P > or = .1011). Body weight-normalized apparent
      oral clearance ranges from 0.061 to 0.089 L/h/kg.

PMID- 19179300
TI  - Quantifying the development of the peripheral naive CD4+ T-cell pool in humans.
AB  - What are the rules that govern a naive T cell's prospects for survival or
      division after export from the thymus into the periphery? To help address these
      questions, we combine data from existing studies with robust mathematical models
      to estimate the absolute contributions of thymopoiesis, peripheral division, and
      loss or differentiation to the human naive CD4+ T-cell pool between the ages of 0
      and 20 years. Despite their decline in frequency in the blood, total body numbers
      of naive CD4+ T cells increase throughout childhood and early adulthood. Our
      analysis shows that postthymic proliferation contributes more than double the
      number of cells entering the pool each day from the thymus. This ratio is
      preserved with age; as the thymus involutes, the average time between naive T
      cell divisions in the periphery lengthens. We also show that the expected
      residence time of naive T cells increases with time. The naive CD4+ T-cell
      population thus becomes progressively less dynamic with age. Together with other
      studies, our results suggest a complex picture of naive T-cell homeostasis in
      which population size, time since export from the thymus, or time since the last
      division can influence a cell's prospects for survival or further divisions.

PMID- 19179301
TI  - Prolonged survival in adults with acute lymphoblastic leukemia after reduced
      intensity conditioning with cord blood or sibling donor transplantation.
AB  - Twenty-two adult acute lymphoblastic leukemia (ALL) patients (21 of 22 in
      complete remission [CR]) received reduced-intensity conditioning followed by
      allogeneic transplantation. All patients were high risk. After a uniform
      preparative regimen (fludarabine 40 mg/m(2) x 5, cyclophosphamide 50 mg/kg, 200
      cGy total body irradiation), patients received either matched related (n=4) or
      umbilical cord (n=18) donor grafts. All patients reached neutrophil engraftment
      and 100% donor chimerism (median, days 10 and 23, respectively). Overall
      survival, treatment-related mortality (TRM) and relapse were 50% (95% confidence
      interval [CI], 27%-73%), 27% (95% CI, 9%-45%), and 36% (95% CI, 14%-58%) at 3
      years, respectively. There were no relapses beyond 2 years. The cumulative
      incidence of acute and chronic graft-versus-host disease was 55% and 45%.
      Hematopoietic cell transplantation in CR1 (n=14) led to significantly less TRM
      (8%, P< .04) and improved overall survival (81%, P< .01). For adults with ALL in
      CR, reduced intensity conditioning allografting results in modest TRM, limited
      risk of relapse, and promising leukemia-free survival. Clinical trial numbers are
      NCT00365287, NCT00305682, and NCT00303719.

PMID- 19179302
TI  - Breaking tolerance to self, circulating natural killer cells expressing
      inhibitory KIR for non-self HLA exhibit effector function after T cell-depleted
      allogeneic hematopoietic cell transplantation.
AB  - Alloreactive natural killer (NK) cells are an important influence on
      hematopoietic stem cell transplantation (HSCT) outcome. In HLA-mismatched HSCT,
      alloreactivity occurs when licensed donor NK cells expressing inhibitory killer
      Ig-like receptors (KIR) for donor MHC class I ligands recognize the lack of the
      class I ligands in the mismatched recipient ("missing self"). Studies in HLA
      matched HSCT, however, have also demonstrated improved outcome in patients
      lacking class I ligands for donor inhibitory KIR ("missing ligand"), indicating
      that classically nonlicensed donor NK cells expressing KIR for non-self MHC class
      I ligands may exhibit functional competence in HSCT. We examined NK function in
      16 recipients of T cell-depleted allografts from HLA-identical or KIR-ligand
      matched donors after myeloablative therapy. After HSCT, nonlicensed NK cells
      expressing inhibitory KIR for non-self class I exhibit robust intracellular IFN
      gamma and cytotoxic response to target cells lacking cognate ligand, gradually
      becoming tolerized to self by day 100. These findings could not be correlated
      with cytokine environment or phenotypic markers of NK development, nor could they
      be attributed to non-KIR receptors such as CD94/NKG2A. These findings confirm
      that NK alloreactivity can occur in HLA-matched HSCT, where tolerance to self is
      either acquired by the stem cell-derived NK cell after exiting the bone marrow or
      where tolerance to self can be temporarily overcome.

PMID- 19179303
TI  - Novel roles for erythroid Ankyrin-1 revealed through an ENU-induced null mouse
      mutant.
AB  - Insights into the role of ankyrin-1 (ANK-1) in the formation and stabilization of
      the red cell cytoskeleton have come from studies on the nb/nb mice, which carry
      hypomorphic alleles of Ank-1. Here, we revise several paradigms established in
      the nb/nb mice through analysis of an N-ethyl-N-nitrosourea (ENU)-induced Ank-1
      null mouse. Mice homozygous for the Ank-1 mutation are profoundly anemic in utero
      and most die perinatally, indicating that Ank-1 plays a nonredundant role in
      erythroid development. The surviving pups exhibit features of severe hereditary
      spherocytosis (HS), with marked hemolysis, jaundice, compensatory extramedullary
      erythropoiesis, and tissue iron overload. Red cell membrane analysis reveals a
      complete loss of ANK-1 protein and a marked reduction in beta-spectrin. As a
      consequence, the red cells exhibit total disruption of cytoskeletal architecture
      and severely altered hemorheologic properties. Heterozygous mutant mice, which
      have wild-type levels of ANK-1 and spectrin in their RBC membranes and normal red
      cell survival and ultrastructure, exhibit profound resistance to malaria, which
      is not due to impaired parasite entry into RBC. These findings provide novel
      insights into the role of Ank-1, and define an ideal model for the study of HS
      and malarial resistance.

PMID- 19179304
TI  - Dysregulation of Frizzled 6 is a critical component of B-cell leukemogenesis in a
      mouse model of chronic lymphocytic leukemia.
AB  - Wnt/Fzd signaling is known to play a key role in development, tissue-specific
      stem-cell maintenance, and tumorigenesis, particularly through the canonical
      pathway involving stabilization of beta-catenin. We have previously shown that
      Fzd9(-/-) mice have a deficiency in pre-B cells at a stage when self-renewing
      division is occurring in preference to further differentiation, before light
      chain immunoglobulin recombination. To determine whether pathologic usurpation of
      this pathway plays a role in B-cell leukemogenesis, we examined the expression of
      Wnt/Fzd pathway genes in the Emu-TCL1 mouse model of chronic lymphocytic
      leukemia. We find that, in the course of leukemogenesis, the expression of Wnt16,
      Wnt10alpha, Fzd1, and most dramatically, Fzd6, is progressively up-regulated in
      the transformed CD5(+) B cells of these mice, as are beta-catenin protein levels.
      Elimination of Fzd6 expression by crossing into Fzd6(-/-) mice significantly
      delays development of chronic lymphocytic leukemia in this model. Our findings
      suggest that the self-renewal signals mediated by Wnt/Fzd that are enlisted
      during B-cell development may be pathologically reactivated in the neoplastic
      transformation of mature B cells.

PMID- 19179306
TI  - Infarction of tumor vessels by NGR-peptide-directed targeting of tissue factor:
      experimental results and first-in-man experience.
AB  - We induced thrombosis of blood vessels in solid tumors in mice by a fusion
      protein consisting of the extracellular domain of tissue factor (truncated tissue
      factor, tTF) and the peptide GNGRAHA, targeting aminopeptidase N (CD13) and the
      integrin alpha(v)beta(3) (CD51/CD61) on tumor vascular endothelium. The designed
      fusion protein tTF-NGR retained its thrombogenic activity as demonstrated by
      coagulation assays. In vivo studies in mice bearing established human
      adenocarcinoma (A549), melanoma (M21), and fibrosarcoma (HT1080) revealed that
      systemic administration of tTF-NGR induced partial or complete thrombotic
      occlusion of tumor vessels as shown by histologic analysis. tTF-NGR, but not
      untargeted tTF, induced significant tumor growth retardation or regression in all
      3 types of solid tumors. Thrombosis induction in tumor vessels by tTF-NGR was
      also shown by contrast enhanced magnetic resonance imaging (MRI). In the human
      fibrosarcoma xenograft model, MRI revealed a significant reduction of tumor
      perfusion by administration of tTF-NGR. Clinical first-in-man application of low
      dosages of this targeted coagulation factor revealed good tolerability and
      decreased tumor perfusion as measured by MRI. Targeted thrombosis in the tumor
      vasculature induced by tTF-NGR may be a promising strategy for the treatment of
      cancer.

PMID- 19179305
TI  - Runx2 induces acute myeloid leukemia in cooperation with Cbfbeta-SMMHC in mice.
AB  - The core-binding factor (CBF) is a master regulator of developmental and
      differentiation programs, and CBF alterations are frequently associated with
      acute leukemia. The role of the CBF member RUNX2 in hematopoiesis is poorly
      understood. Genetic evidence suggests that deregulation of Runx2 may cause
      myeloid leukemia in mice expressing the fusion oncogene Cbfb-MYH11. In this
      study, we show that sustained expression of Runx2 modulates Cbfbeta-smooth muscle
      myosin heavy chain (SMMHC)-mediated myeloid leukemia development. Expression of
      Runx2 is high in the hematopoietic stem cell compartment and decreases during
      myeloid differentiation. Sustained Runx2 expression hinders myeloid progenitor
      differentiation capacity and represses expression of CBF targets Csf1R, Mpo,
      Cebpd, the cell cycle inhibitor Cdkn1a, and myeloid markers Cebpa and Gfi1. In
      addition, full-length Runx2 cooperates with Cbfbeta-SMMHC in leukemia development
      in transplantation assays. Furthermore, we show that the nuclear matrix-targeting
      signal and DNA-binding runt-homology domain of Runx2 are essential for its
      leukemogenic activity. Conversely, Runx2 haplo-insufficiency delays the onset and
      reduces the incidence of acute myeloid leukemia. Together, these results indicate
      that Runx2 is expressed in the stem cell compartment, interferes with
      differentiation and represses CBF targets in the myeloid compartment, and
      modulates the leukemogenic function of Cbfbeta-SMMHC in mouse leukemia.

PMID- 19179307
TI  - Scavenger receptor class B type I-mediated uptake of serum cholesterol is
      essential for optimal adrenal glucocorticoid production.
AB  - Impaired scavenger receptor class B type I (SR-BI)-mediated uptake of HDL
      cholesterol esters (HDL-CE) induces adrenal insufficiency in mice. Humans contain
      an alternative route of HDL-CE clearance, namely through the transfer by
      cholesteryl ester transfer protein (CETP) to apolipoprotein B lipoproteins for
      subsequent uptake via the LDL receptor. In this study, we determined whether CETP
      can compensate for loss of adrenal SR-BI. Transgenic expression of human CETP
      (CETP Tg) in SR-BI knockout (KO) mice increased adrenal HDL-CE clearance from 33
      58% of the control value. SR-BI KO/CETP Tg and SR-BI KO mice displayed adrenal
      hypertrophy due to equally high plasma adrenocorticotropic hormone levels.
      Adrenal cholesterol levels and plasma corticosterone levels were 38-52% decreased
      in SR-BI KO mice with and without CETP expression. SR-BI KO/CETP Tg mice also
      failed to increase their corticosterone level after lipopolysaccharide challenge,
      leading to an identical >4-fold increased tumor necrosis factor-alpha response
      compared with controls. These data indicate that uptake of CE via other routes
      than SR-BI is not sufficient to generate the cholesterol pool needed for optimal
      adrenal steroidogenesis. In conclusion, we have shown that CETP-mediated transfer
      of HDL-CE is not able to reverse adrenal insufficiency in SR-BI knockout mice.
      Thus, SR-BI-mediated uptake of serum cholesterol is essential for optimal adrenal
      function.

PMID- 19179309
TI  - Videos in clinical medicine. Blood-pressure measurement.

PMID- 19179308
TI  - Mass spectrometric determination of apolipoprotein molecular stoichiometry in
      reconstituted high density lipoprotein particles.
AB  - Plasma HDL-cholesterol and apolipoprotein A-I (apoA-I) levels are strongly
      inversely associated with cardiovascular disease. However, the structure and
      protein composition of HDL particles is complex, as native and synthetic
      discoidal and spherical HDL particles can have from two to five apoA-I molecules
      per particle. To fully understand structure-function relationships of HDL, a
      method is required that is capable of directly determining the number of
      apolipoprotein molecules in heterogeneous HDL particles. Chemical cross-linking
      followed by SDS polyacrylamide gradient gel electrophoresis has been previously
      used to determine apolipoprotein stoichiometry in HDL particles. However, this
      method yields ambiguous results due to effects of cross-linking on protein
      conformation and, subsequently, its migration pattern on the gel. Here, we
      describe a new method based on cross-linking chemistry followed by MALDI mass
      spectrometry that determines the absolute mass of the cross-linked complex,
      thereby correctly determining the number of apolipoprotein molecules in a given
      HDL particle. Using well-defined, homogeneous, reconstituted apoA-I-containing
      HDL, apoA-IV-containing HDL, as well as apoA-I/apoA-II-containing HDL, we have
      validated this method. The method has the capability to determine the molecular
      ratio and molecular composition of apolipoprotein molecules in complex
      reconstituted HDL particles.

PMID- 19179310
TI  - Images in clinical medicine. Traumatic diaphragmatic rupture with intrathoracic
      liver herniation.

PMID- 19179311
TI  - Universal health insurance coverage or economic relief--a false choice.

PMID- 19179312
TI  - Antibiotic-resistant bugs in the 21st century--a clinical super-challenge.

PMID- 19179313
TI  - Fighting on.

PMID- 19179314
TI  - Gene therapy for immunodeficiency due to adenosine deaminase deficiency.
AB  - BACKGROUND: We investigated the long-term outcome of gene therapy for severe
      combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a
      fatal disorder of purine metabolism and immunodeficiency. METHODS: We infused
      autologous CD34+ bone marrow cells transduced with a retroviral vector containing
      the ADA gene into 10 children with SCID due to ADA deficiency who lacked an HLA
      identical sibling donor, after nonmyeloablative conditioning with busulfan.
      Enzyme-replacement therapy was not given after infusion of the cells. RESULTS:
      All patients are alive after a median follow-up of 4.0 years (range, 1.8 to 8.0).
      Transduced hematopoietic stem cells have stably engrafted and differentiated into
      myeloid cells containing ADA (mean range at 1 year in bone marrow lineages, 3.5
      to 8.9%) and lymphoid cells (mean range in peripheral blood, 52.4 to 88.0%).
      Eight patients do not require enzyme-replacement therapy, their blood cells
      continue to express ADA, and they have no signs of defective detoxification of
      purine metabolites. Nine patients had immune reconstitution with increases in T
      cell counts (median count at 3 years, 1.07x10(9) per liter) and normalization of
      T-cell function. In the five patients in whom intravenous immune globulin
      replacement was discontinued, antigen-specific antibody responses were elicited
      after exposure to vaccines or viral antigens. Effective protection against
      infections and improvement in physical development made a normal lifestyle
      possible. Serious adverse events included prolonged neutropenia (in two
      patients), hypertension (in one), central-venous-catheter-related infections (in
      two), Epstein-Barr virus reactivation (in one), and autoimmune hepatitis (in
      one). CONCLUSIONS: Gene therapy, combined with reduced-intensity conditioning, is
      a safe and effective treatment for SCID in patients with ADA deficiency.
      (ClinicalTrials.gov numbers, NCT00598481 and NCT00599781.)

PMID- 19179315
TI  - Long-term consequences of kidney donation.
AB  - BACKGROUND: The long-term renal consequences of kidney donation by a living donor
      are attracting increased appropriate interest. The overall evidence suggests that
      living kidney donors have survival similar to that of nondonors and that their
      risk of end-stage renal disease (ESRD) is not increased. Previous studies have
      included relatively small numbers of donors and a brief follow-up period.
      METHODS: We ascertained the vital status and lifetime risk of ESRD in 3698 kidney
      donors who donated kidneys during the period from 1963 through 2007; from 2003
      through 2007, we also measured the glomerular filtration rate (GFR) and urinary
      albumin excretion and assessed the prevalence of hypertension, general health
      status, and quality of life in 255 donors. RESULTS: The survival of kidney donors
      was similar to that of controls who were matched for age, sex, and race or ethnic
      group. ESRD developed in 11 donors, a rate of 180 cases per million persons per
      year, as compared with a rate of 268 per million per year in the general
      population. At a mean (+/-SD) of 12.2+/-9.2 years after donation, 85.5% of the
      subgroup of 255 donors had a GFR of 60 ml per minute per 1.73 m(2) of body
      surface area or higher, 32.1% had hypertension, and 12.7% had albuminuria. Older
      age and higher body-mass index, but not a longer time since donation, were
      associated with both a GFR that was lower than 60 ml per minute per 1.73 m(2) and
      hypertension. A longer time since donation, however, was independently associated
      with albuminuria. Most donors had quality-of-life scores that were better than
      population norms, and the prevalence of coexisting conditions was similar to that
      among controls from the National Health and Nutrition Examination Survey (NHANES)
      who were matched for age, sex, race or ethnic group, and body-mass index.
      CONCLUSIONS: Survival and the risk of ESRD in carefully screened kidney donors
      appear to be similar to those in the general population. Most donors who were
      studied had a preserved GFR, normal albumin excretion, and an excellent quality
      of life.

PMID- 19179317
TI  - Behavioral management for anorexia nervosa.

PMID- 19179316
TI  - Weight loss to treat urinary incontinence in overweight and obese women.
AB  - BACKGROUND: Obesity is an established and modifiable risk factor for urinary
      incontinence, but conclusive evidence for a beneficial effect of weight loss on
      urinary incontinence is lacking. METHODS: We randomly assigned 338 overweight and
      obese women with at least 10 urinary-incontinence episodes per week to an
      intensive 6-month weight-loss program that included diet, exercise, and behavior
      modification (226 patients) or to a structured education program (112 patients).
      RESULTS: The mean (+/-SD) age of the participants was 53+/-11 years. The body
      mass index (BMI) (the weight in kilograms divided by the square of the height in
      meters) and the weekly number of incontinence episodes as recorded in a 7-day
      diary of voiding were similar in the intervention group and the control group at
      baseline (BMI, 36+/-6 and 36+/-5, respectively; incontinence episodes, 24+/-18
      and 24+/-16, respectively). The women in the intervention group had a mean weight
      loss of 8.0% (7.8 kg), as compared with 1.6% (1.5 kg) in the control group
      (P<0.001). After 6 months, the mean weekly number of incontinence episodes
      decreased by 47% in the intervention group, as compared with 28% in the control
      group (P=0.01). As compared with the control group, the intervention group had a
      greater decrease in the frequency of stress-incontinence episodes (P=0.02), but
      not of urge-incontinence episodes (P=0.14). A higher proportion of the
      intervention group than of the control group had a clinically relevant reduction
      of 70% or more in the frequency of all incontinence episodes (P<0.001), stress
      incontinence episodes (P=0.009), and urge-incontinence episodes (P=0.04).
      CONCLUSIONS: A 6-month behavioral intervention targeting weight loss reduced the
      frequency of self-reported urinary-incontinence episodes among overweight and
      obese women as compared with a control group. A decrease in urinary incontinence
      may be another benefit among the extensive health improvements associated with
      moderate weight reduction. (ClinicalTrials.gov number, NCT00091988.)

PMID- 19179318
TI  - Images in clinical medicine. Metallic mercury embolism to the hand.

PMID- 19179319
TI  - Case records of the Massachusetts General Hospital. Case 4-2009. A 39-year-old
      pregnant woman with fever after a trip to Africa.

PMID- 19179320
TI  - Gene therapy fulfilling its promise.

PMID- 19179321
TI  - Cautious optimism concerning long-term safety of kidney donation.

PMID- 19179322
TI  - Clinical decisions. Care of an unresponsive patient with a poor prognosis.

PMID- 19179323
TI  - Getting to the heart of proteomics.

PMID- 19179324
TI  - Insulin therapy in very-low-birth-weight infants.

PMID- 19179325
TI  - Effectiveness of maternal influenza immunization.

PMID- 19179326
TI  - Uric acid and cardiovascular risk.

PMID- 19179327
TI  - The statins in preventive cardiology.

PMID- 19179328
TI  - Eculizumab for atypical hemolytic-uremic syndrome.

PMID- 19179329
TI  - Eculizumab for congenital atypical hemolytic-uremic syndrome.

PMID- 19179330
TI  - Significance of the dissociation of Dna2 by flap endonuclease 1 to Okazaki
      fragment processing in Saccharomyces cerevisiae.
AB  - Okazaki fragments are initiated by short RNA/DNA primers, which are displaced
      into flap intermediates for processing. Flap endonuclease 1 (FEN1) and Dna2 are
      responsible for flap cleavage. Replication protein A (RPA)-bound flaps inhibit
      cleavage by FEN1 but stimulate Dna2, requiring that Dna2 cleaves prior to FEN1.
      Upon cleavage, Dna2 leaves a short flap, which is then cut by FEN1 forming a nick
      for ligation. Both enzymes require a flap with a free 5'-end for tracking to the
      cleavage sites. Previously, we demonstrated that FEN1 disengages the tracking
      mechanism of Dna2 to remove it from the flap. To determine why the disengagement
      mechanism evolved, we measured FEN1 dissociation of Dna2 on short RNA and DNA
      flaps, which occur during flap processing. Dna2 tracked onto these flaps but
      could not cleave, presenting a block to FEN1 entry. However, FEN1 disengaged
      these nonproductively bound Dna2 molecules, proceeding on to conduct proper
      cleavage. These results clarify the importance of disengagement. Additional
      results showed that flap substrate recognition and tracking by FEN1, as occur
      during fragment processing, are required for effective displacement of the flap
      bound Dna2. Dna2 was recently shown to dissociate flap-bound RPA, independent of
      cleavage. Using a nuclease-defective Dna2 mutant, we reconstituted the sequential
      dissociation reactions in the proposed RPA/Dna2/FEN1 pathway showing that, even
      without cutting, Dna2 enables FEN1 to cleave RPA-coated flaps. In summary, RPA,
      Dna2, and FEN1 have evolved highly coordinated binding properties enabling one
      protein to succeed the next for proper and efficient Okazaki flap processing.

PMID- 19179331
TI  - ISC1-dependent metabolic adaptation reveals an indispensable role for
      mitochondria in induction of nuclear genes during the diauxic shift in
      Saccharomyces cerevisiae.
AB  - Growth of Saccharomyces cerevisiae following glucose depletion (the diauxic
      shift) depends on a profound metabolic adaptation accompanied by a global
      reprogramming of gene expression. In this study, we provide evidence for a
      heretofore unsuspected role for Isc1p in mediating this reprogramming. Initial
      studies revealed that yeast cells deleted in ISC1, the gene encoding inositol
      sphingolipid phospholipase C, which resides in mitochondria in the post-diauxic
      phase, showed defective aerobic respiration in the post-diauxic phase but
      retained normal intrinsic mitochondrial functions, including intact mitochondrial
      DNA, normal oxygen consumption, and normal mitochondrial polarization. Microarray
      analysis revealed that the Deltaisc1 strain failed to up-regulate genes required
      for nonfermentable carbon source metabolism during the diauxic shift, thus
      suggesting a mechanism for the defective supply of respiratory substrates into
      mitochondria in the post-diauxic phase. This defect in regulating nuclear gene
      induction in response to a defect in a mitochondrial enzyme raised the
      possibility that mitochondria may initiate diauxic shift-associated regulation of
      nucleus-encoded genes. This was established by demonstrating that in respiratory
      deficient petite cells these genes failed to be up-regulated across the diauxic
      shift in a manner similar to the Deltaisc1 strain. Isc1p- and mitochondrial
      function-dependent genes significantly overlapped with Adr1p-, Snf1p-, and Cat8p
      dependent genes, suggesting some functional link among these factors. However,
      the retrograde response was not activated in Deltaisc1, suggesting that the
      response of Deltaisc1 cannot be simply attributed to mitochondrial dysfunction.
      These results suggest a novel role for Isc1p in allowing the reprogramming of
      gene expression during the transition from anaerobic to aerobic metabolism.

PMID- 19179332
TI  - Combining Inhibitor Resistance-conferring Mutations in Cytochrome b Creates
      Conditional Synthetic Lethality in Saccharomyces cerevisiae.
AB  - The mitochondrial cytochrome bc(1) complex is an essential respiratory enzyme in
      oxygen-utilizing eukaryotic cells. Its core subunit, cytochrome b, contains two
      sites, center P and center N, that participate in the electron transfer activity
      of the bc(1) complex and that can be blocked by specific inhibitors. In yeast,
      there are various point mutations that confer inhibitor resistance at center P or
      center N. However, there are no yeast strains in which the bc(1) complex is
      resistant to both center P and center N inhibitors. We attempted to create such
      strains by crossing yeast strains with inhibitor-resistant mutations at center P
      with yeast strains with inhibitor-resistant mutations at center N.
      Characterization of yeast colonies emerging from the cross revealed that there
      were multiple colonies resistant against either inhibitor alone but that the
      mutational changes were ineffective when combined and when the yeast were grown
      in the presence of both inhibitors. Inhibitor titrations of bc(1) complex
      activities in mitochondrial membranes from the various yeast mutants showed that
      a mutation that confers resistance to an inhibitor at center P, when combined
      with a mutation that confers resistance to an inhibitor at center N, eliminates
      or markedly decreases the resistance conferred by the center N mutation. These
      results indicate that there is a pathway for structural communication between the
      two active sites of cytochrome b and open new possibilities for the utilization
      of center N as a potential drug target.

PMID- 19179333
TI  - HSF1-mediated BAG3 expression attenuates apoptosis in 4-hydroxynonenal-treated
      colon cancer cells via stabilization of anti-apoptotic Bcl-2 proteins.
AB  - 4-Hydroxynonenal (HNE) is a pro-apoptotic electrophile generated during the
      spontaneous decomposition of oxidized lipids. We have previously shown that HNE
      activates the transcription factor, heat shock factor 1 (HSF1), and promotes
      cytoprotective heat shock gene expression and that silencing HSF1 sensitizes the
      colon cancer cell line RKO to HNE-induced apoptosis. Here we report a reduction
      in the anti-apoptotic proteins Bcl-X(L), Mcl-1, and Bcl-2 in HSF1-silenced RKO
      cells, and we examine the underlying mechanism. To investigate the regulation of
      the Bcl-2 family by HSF1, microarray analysis of gene expression was performed.
      We observed that the Hsp70 co-chaperone, BAG3 (Bcl-2-associated athanogene domain
      3), is strongly induced by HNE in control but not in HSF1-silenced colon cancer
      cells. Silencing BAG3 expression with small interfering RNA caused a dramatic
      reduction in Bcl-X(L), Mcl-1, and Bcl-2 protein levels in colon cancer cells and
      increased apoptosis, similar to the effect of silencing HSF1. Also,
      immunoprecipitation experiments indicate specific interactions between BAG3,
      Hsp70, and the Bcl-2 family member, Bcl-X(L). Overall, our data reveal that BAG3
      is HSF1-inducible and has a unique role facilitating cancer cell survival during
      pro-apoptotic stress by stabilizing the level of Bcl-2 family proteins.

PMID- 19179334
TI  - The Hantavirus Glycoprotein G1 Tail Contains Dual CCHC-type Classical Zinc
      Fingers.
AB  - Hantaviruses are distributed worldwide and can cause a hemorrhagic fever or a
      cardiopulmonary syndrome in humans. Mature virions consist of RNA genome,
      nucleocapsid protein, RNA polymerase, and two transmembrane glycoproteins, G1 and
      G2. The ectodomain of G1 is surface-exposed; however, it has a 142-residue C
      terminal cytoplasmic tail that plays important roles in viral assembly and host
      pathogen interaction. Here we show by NMR, circular dichroism spectroscopy, and
      mutagenesis that a highly conserved cysteine/histidine-rich region in the G1 tail
      of hantaviruses forms two CCHC-type classical zinc fingers. Unlike classical zinc
      fingers, however, the two G1 zinc fingers are intimately joined together, forming
      a compact domain with a unique fold. We discuss the implication of the hantaviral
      G1 zinc fingers in viral assembly and host-pathogen interaction.

PMID- 19179335
TI  - Dopamine D4 Receptors Regulate GABAA Receptor Trafficking via an
      Actin/Cofilin/Myosin-dependent Mechanism.
AB  - The GABA(A) receptor-mediated inhibitory transmission in prefrontal cortex (PFC)
      is implicated in cognitive processes such as working memory. Our previous study
      has found that GABA(A)R current is subject to the regulation of dopamine D(4)
      receptors, a PFC-enriched neuromodulator critically involved in various mental
      disorders associated with PFC dysfunction. In this study, we have investigated
      the cellular mechanism underlying D(4) modulation of GABA(A)Rs. We found that the
      density of surface clusters of GABA(A)R beta2/3 subunits was reduced by D(4),
      suggesting that the D(4) reduction of GABA(A)R current is associated with a
      decrease in functional GABA(A)Rs at the plasma membrane. Moreover, the D(4)
      reduction of GABA(A)R current was blocked by the actin stabilizer phalloidin and
      was occluded by the actin destabilizer latrunculin, suggesting that D(4)
      regulates GABA(A)R trafficking via an actin-dependent mechanism. Cofilin, a major
      actin depolymerizing factor whose activity is strongly increased by
      dephosphorylation at Ser(3), provides the possible link between D(4) signaling
      and the actin dynamics. Because myosin motor proteins are important for the
      transport of vesicles along actin filaments, we also tested the potential
      involvement of myosin in D(4) regulation of GABA(A)R trafficking. We found that
      dialysis with a myosin peptide, which competes with endogenous myosin proteins
      for actin-binding sites, prevented the D(4) reduction of GABA(A)R current. These
      results suggest that D(4) receptor activation increases cofilin activity
      presumably via its dephosphorylation, resulting in actin depolymerization, thus
      causing a decrease in the myosin-based transport of GABA(A)R clusters to the
      surface.

PMID- 19179336
TI  - Cockayne syndrome group B protein stimulates repair of formamidopyrimidines by
      NEIL1 DNA glycosylase.
AB  - Cockayne syndrome (CS) is a premature aging condition characterized by
      sensitivity to UV radiation. However, this phenotype does not explain the
      progressive neurodegeneration in CS patients. It could be due to the
      hypersensitivity of CSB-deficient cells to oxidative stress. So far most studies
      on the role of CSB in repair of oxidatively induced DNA lesions have focused on
      7,8-dihydro-8-oxoguanine. This study examines the role of CSB in the repair of
      formamidopyrimidines 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) and
      4,6-diamino-5-formamidopyrimidine (FapyAde), which are substrates for
      endonuclease VIII-like (NEIL1) DNA glycosylase. Results presented here show that
      csb(-/-) mice have a higher level of endogenous FapyAde and FapyGua in DNA from
      brain and kidney than wild type mice as well as higher levels of endogenous
      FapyAde in genomic DNA and mtDNA from liver. In addition, CSB stimulates NEIL1
      incision activity in vitro, and CSB and NEIL1 co-immunoprecipitate and co
      localize in HeLa cells. When CSB and NEIL1 are depleted from HeLa cells by short
      hairpin RNA knockdown, repair of induced FapyGua is strongly inhibited. These
      results suggest that CSB plays a role in repair of formamidopyrimidines, possibly
      by interacting with and stimulating NEIL1, and that accumulation of such
      modifications may have a causal role in the pathogenesis of CS.

PMID- 19179337
TI  - Phosphorylation of Nephrin Triggers Ca2+ Signaling by Recruitment and Activation
      of Phospholipase C-{gamma}1.
AB  - A specialized intercellular junction between podocytes, known as the slit
      diaphragm (SD), forms the essential structural frame-work for glomerular
      filtration in the kidney. In addition, mounting evidence demonstrates that the SD
      also plays a crucial role as a signaling platform in physiological and
      pathological states. Nephrin, the major component of the SD, is tyrosine
      phosphorylated by a Src family tyrosine kinase, Fyn, in developing or injured
      podocytes, recruiting Nck to Nephrin via its Src homology 2 domain to regulate
      dynamic actin remodeling. Dysregulated Ca(2+) homeostasis has also been
      implicated in podocyte damage, but the mechanism of how podocytes respond to
      injury is largely unknown. Here we have identified phospholipase C-gamma1 (PLC
      gamma1) as a novel phospho-Nephrin-binding protein. When HEK293T cells expressing
      a chimeric protein consisting of CD8 and Nephrin cytoplasmic domain (CD) were
      treated with anti-CD8 and anti-mouse antibodies, clustering of Nephrin and
      phosphorylation of Nephrin-CD were induced. Upon this clustering, PLC-gamma1 was
      bound to phosphorylated Nephrin Tyr-1204, which induced translocation of PLC
      gamma1 from cytoplasm to the CD8/Nephrin cluster on the plasma membrane. The
      recruitment of PLC-gamma1 to Nephrin activated PLC-gamma1, as detected by
      phosphorylation of PLC-gamma1 Tyr-783 and increase in inositol 1,4,5
      trisphosphate level. We also found that Nephrin Tyr-1204 phosphorylation triggers
      the Ca(2+) response in a PLC-gamma1-dependent fashion. Furthermore, PLC-gamma1 is
      significantly phosphorylated in injured podocytes in vivo. Given the profound
      effect of PLC-gamma in diverse cellular functions, regulation of the Ca(2+)
      signaling by Nephrin may be important in modulating the glomerular filtration
      barrier function.

PMID- 19179338
TI  - Cyclin-dependent Kinases Phosphorylate the Cytomegalovirus RNA Export Protein
      pUL69 and Modulate Its Nuclear Localization and Activity.
AB  - Replication of human cytomegalovirus (HCMV) is subject to regulation by cellular
      protein kinases. Recently, we and others reported that inhibition of cyclin
      dependent protein kinases (CDKs) or the viral CDK ortholog pUL97 can induce
      intranuclear speckled aggregation of the viral mRNA export factor, pUL69. Here we
      provide the first evidence for a direct regulatory role of CDKs on pUL69
      functionality. Although replication of all HCMV strains was dependent on CDK
      activity, we found strain-specific differences in the amount of CDK inhibitor
      induced pUL69 aggregate formation. In all cases analyzed, the inhibitor-induced
      pUL69 aggregates were clearly localized within viral replication centers but not
      subnuclear splicing, pore complex, or aggresome structures. The CDK9 and cyclin
      T1 proteins colocalized with these pUL69 aggregates, whereas other CDKs behaved
      differently. Phosphorylation analyses in vivo and in vitro demonstrated pUL69 was
      strongly phosphorylated in HCMV-infected fibroblasts and that CDKs represent a
      novel class of pUL69-phosphorylating kinases. Moreover, the analysis of CDK
      inhibitors in a pUL69-dependent nuclear mRNA export assay provided evidence for
      functional impairment of pUL69 under suppression of CDK activity. Thus, our data
      underline the crucial importance of CDKs for HCMV replication, and indicate a
      direct impact of CDK9-cyclin T1 on the nuclear localization and activity of the
      viral regulator pUL69.

PMID- 19179339
TI  - Chromogranin A promotes peptide hormone sorting to mobile granules in
      constitutively and regulated secreting cells: role of conserved N- and C-terminal
      peptides.
AB  - Chromogranin A (CgA) has been proposed to play a major role in the formation of
      dense-core secretory granules (DCGs) in neuroendocrine cells. Here, we took
      advantage of unique features of the frog CgA (fCgA) to assess the role of this
      granin and its potential functional determinants in hormone sorting during DCG
      biogenesis. Expression of fCgA in the constitutively secreting COS-7 cells
      induced the formation of mobile vesicular structures, which contained
      cotransfected peptide hormones. The fCgA and the hormones coexpressed in the
      newly formed vesicles could be released in a regulated manner. The N- and C
      terminal regions of fCgA, which exhibit remarkable sequence conservation with
      their mammalian counterparts were found to be essential for the formation of the
      mobile DCG-like structures in COS-7 cells. Expression of fCgA in the corticotrope
      AtT20 cells increased pro-opiomelanocortin levels in DCGs, whereas the expression
      of N- and C-terminal deletion mutants provoked retention of the hormone in the
      Golgi area. Furthermore, fCgA, but not its truncated forms, promoted pro
      opiomelanocortin sorting to the regulated secretory pathway. These data
      demonstrate that CgA has the intrinsic capacity to induce the formation of mobile
      secretory granules and to promote the sorting and release of peptide hormones.
      The conserved terminal peptides are instrumental for these activities of CgA.

PMID- 19179340
TI  - Neurokinin 1 receptor mediates membrane blebbing in HEK293 cells through a
      Rho/Rho-associated coiled-coil kinase-dependent mechanism.
AB  - We have investigated the effect of neurokinin 1 receptor (NK1R) agonists on
      HEK293 cells transfected with the NK1R receptor. The NK1R receptor mediates
      dramatic shape changes that include contractions of the membrane cortex resulting
      in membrane bleb formation. We have found that the cell shape changes correlate
      with changes in electrical impedance measured in cellular monolayers. The shape
      and impedance changes were prevented after preincubation with NK1R antagonists
      aprepitant and L-73060. Although bleb formation usually heralds apoptotic cell
      death, we have found that NK1R-mediated cellular blebbing does not associate with
      apoptosis. Preincubation with a cell-permeable derivative of C3 transferase that
      blocks Rho or with the Rho-associated coiled-coil kinase inhibitor Y27632
      completely prevented NK1R-induced shape and impedance changes. Blebbing was also
      completely inhibited by ML-9, a myosin light chain kinase inhibitor. Furthermore,
      the phospholipase C inhibitor U73,122 did not interfere with the effect of
      Substance P (SP) on cellular morphology and cellular impedance but completely
      blocked SP-induced intracellular calcium increase, indicating that the blebbing
      is a process independent of intracellular calcium elevations. Blebbing is a
      protein kinase C-independent process, since the nonselective protein kinase C
      inhibitor GF109203X did not interfere with SP-induced effects. Based on these
      results, we provide the first evidence that NK1R receptor-ligand interaction can
      cause apoptosis-independent cellular blebbing and that this process is mediated
      by the Rho/Rho-associated coiled-coil kinase pathway.

PMID- 19179341
TI  - Engineering enzymes for improved catalytic efficiency: a computational study of
      site mutagenesis in epothilone-B hydroxylase.
AB  - Epothilone F, 21-hydroxyl-epothilone B, is an intermediate in the synthesis of
      BMS-310705, an antitumor compound that has been evaluated in Phase I clinical
      trials. A bioconversion process utilizing the Gram-positive bacterium
      Amycolatopsis orientalis was used to prepare epothilone F from epothilone B. In
      order to improve the yield of epothilone F, a mutagenesis program was performed
      with the goal of engineering the epothilone-B hydroxylase (EBH) enzyme to improve
      the yield of epothilone F through oxidative biotransformation. The mutations in
      EBH increased the yield of epothilone F from 21% in the recombinant expression
      system to higher than 80% utilizing the best EBH mutants. The studies described
      here show how a homology model of EBH was used to obtain an understanding of the
      possible mechanism that led to improved yield of epothilone F in the mutated
      enzymes. A novel aspect of this study is that it provides some insight into how
      mutations distant from the binding site can affect enzyme activity.

PMID- 19179342
TI  - Advanced life support update.
AB  - INTRODUCTION: Cardiac arrest is a common emergency in acute hospitals. The
      Resuscitation Council (UK) Advanced Life Support Guidelines provide a systematic
      approach to cardiac arrest recognition, treatment and aftercare. This review
      provides an update on the current treatment guidelines and identifies areas where
      these may be strengthened. METHODS: The evidence informing the 2005 Resuscitation
      Guidelines is reviewed. New evidence since the publication of the guidelines was
      identified by searching Medline (December 2005-December 2008) with the term heart
      arrest or advanced life support. RESULTS: Opportunities for strengthening the
      chain of survival exist for each link. These include better recognition of
      critically ill patients at risk of cardiac arrest, improved quality of
      cardiopulmonary resuscitation, defibrillation strategies, which minimize pre- and
      post-shock pauses and development of post-resuscitation care bundles. CONCLUSION:
      Emerging evidence suggests opportunities where Resuscitation Guidelines could be
      strengthened by focusing on specific aspects of the chain of survival.

PMID- 19179343
TI  - Cardiac radionuclide imaging in stable coronary artery disease and acute coronary
      syndromes.
AB  - INTRODUCTION: The increasing number of available cardiac imaging techniques has
      made the investigation of coronary artery disease (CAD) more complex. Appropriate
      patient referral depends on an understanding of the pre-test likelihood of CAD
      and the information provided by each test. SOURCES OF DATA: This article
      describes myocardial perfusion scintigraphy (MPS) and summarizes evidence for its
      role in stable CAD and acute coronary syndromes with particular reference to
      current guidelines. AREAS OF AGREEMENT: MPS has been extensively validated for
      the cost-effective diagnosis and prognosis of functionally significant CAD in
      both the acute and chronic settings. Its use is emphasized in the current NICE,
      national and international guidelines. AREAS OF CONTROVERSY: Although normal MPS
      is associated with good outcomes, assessments of subclinical atherosclerosis such
      as coronary artery calcium scoring and computed tomography coronary angiography
      (CTA) demonstrate that non-flow-limiting CAD remains prognostically important.
      GROWING POINTS: Technological developments, such as attenuation correction to
      improve diagnostic accuracy or analysis of left ventricular phase to detect
      dyssynchrony, carry the possibility of increasing the information that can be
      usefully gained from a single MPS study. AREAS TIMELY FOR DEVELOPING RESEARCH: Of
      particular importance will be the role of MPS in an integrated imaging strategy
      that involves both anatomical and functional cardiac assessments. The use of
      hybrid technology that combines techniques such as MPS and CTA into a single
      imaging unit requires careful consideration with regard to diagnostic usefulness
      and cost-effectiveness.

PMID- 19179344
TI  - Differentiation of germ cells and gametes from stem cells.
AB  - BACKGROUND: Advances in stem cell research have opened new perspectives for
      regenerative and reproductive medicine. Stem cells (SC) can differentiate under
      appropriate in vitro and in vivo conditions into different cell types. Several
      groups have reported their ability to differentiate SCs into germline cells, and
      some of them have been successful in obtaining male and female gamete-like cells
      by using different methodologies. METHODS: This review summarizes the current
      knowledge in this field and emphasizes significant embryological, genetic and
      epigenetic aspects of germ cells and gametes in vitro differentiation in humans
      and other species, highlighting major obstacles that need to be overcome for
      successful gametogenesis in culture: studies reporting development of germ cell
      like cells from murine and human embryonic (ESC) and somatic SCs are critically
      reviewed. RESULTS: Published studies indicate that germ cells can be consistently
      differentiated from mouse and human ESC. However, further differentiation of germ
      cells through gametogenesis still has important genetic and epigenetic obstacles
      to be efficient. CONCLUSIONS: Differentiation of germ cells from SCs has the
      potential of becoming a future source of gametes for research use, although
      further investigation is needed to understand and develop the appropriate niches
      and culture conditions. Additionally, if genetic and epigenetic methodological
      limitations could be solved, therapeutic opportunities could be also considered.

PMID- 19179345
TI  - Commentary: 'Is the social world flat? W.S. Robinson and the ecologic fallacy'.

PMID- 19179346
TI  - Ecological correlations and the behavior of individuals.

PMID- 19179348
TI  - Revisiting Robinson: the perils of individualistic and ecologic fallacy.
AB  - BACKGROUND: W S Robinson made a seminal contribution by demonstrating that
      correlations for the same two variables can be different at the individual and
      ecologic level. This study reanalyzes and historically situates Robinson's
      influential study that laid the foundation for the primacy of analyzing data at
      only the individual level. METHODS: We applied a binomial multilevel logistic
      model to analyse variation in illiteracy as enumerated by the 1930 US. Census
      (the same data as used by Robinson). The outcome was log odds of being
      illiterate, while predictors were race/nativity ('native whites', 'foreign-born
      whites' and 'negroes') at the individual-level, and presence of Jim Crow
      segregation laws for education at the state-level. We conducted historical
      research to identify the social and scientific context within which Robinson's
      study was produced and favourably received. RESULTS: Empirically, the substantial
      state variations in illiteracy could not be accounted by the states'
      race/nativity composition. Different approaches to modelling state-effects
      yielded considerably attenuated associations at the individual-level between
      illiteracy and race/nativity. Furthermore, state variation in illiteracy was
      different across the race/nativity groups, with state variation being largest for
      whites and least for foreign-born whites. Strong effects of Jim Crow education
      laws on illiteracy were observed with the effect being strongest for blacks.
      Historically, Robinson's study was consonant with the post-World War II
      ascendancy of methodological individualism. CONCLUSION: Applying a historically
      informed multilevel perspective to Robinson's profoundly influential study, we
      demonstrate that meaningful analysis of individual-level relationships requires
      attention to substantial heterogeneity in state characteristics. The implication
      is that perils are posed by not only ecological fallacy but also individualistic
      fallacy. Multilevel thinking, grounded in historical and spatiotemporal context,
      is thus a necessity, not an option.

PMID- 19179349
TI  - Constitutive expression of a trypsin protease inhibitor confers multiple stress
      tolerance in transgenic tobacco.
AB  - Protease inhibitors have been reported to confer insect resistance in transgenic
      plants, except for a rice protease inhibitor that conferred drought tolerance in
      transgenic rice plants. We have cloned a protease inhibitor of tobacco that is
      expressed under treatment with ABA, hydrogen peroxide, methyl jasmonate and
      wounding. The cDNA codes for a six-domain serine protease inhibitor with a
      deduced sequence of 396 amino acids. We have generated transgenic tobacco plants
      expressing the protease inhibitor constitutively under the 35S promoter. When
      analyzed in the T(2) generation, these transgenic plants exhibited tolerance to
      sodium chloride, variable pH and sorbitol, together with the expected resistance
      to the insect pests Spodoptera litura and Helicoverpa armigera. The transgenic
      plants showed enhanced seed germination, root length and root-shoot ratio,
      significantly enhanced total chlorophyll content and reduced thiobarbituric acid
      reactive substances under stress. Under sodium chloride treatment, the transgenic
      plants have enhanced protease inhibitor activity. The transgenic plants exhibited
      a higher potassium content and an optimum Na+/K+ ratio. To our knowledge, this is
      the first report of transgenic plants with constitutive protease inhibitor
      expression showing tolerance to a wide range variable pH in the culture medium
      along with other stresses.

PMID- 19179350
TI  - The 14-3-3 protein GF14c acts as a negative regulator of flowering in rice by
      interacting with the florigen Hd3a.
AB  - Hd3a and FT proteins have recently been proposed to act as florigens in rice and
      Arabidopsis, respectively; however, the molecular mechanisms of their function
      remain to be determined. In this study, we identified GF14c (a 14-3-3 protein) as
      an Hd3a-interacting protein in a yeast two-hybrid screen. In vitro and in vivo
      experiments, using a combination of pull-down assays and bimolecular fluorescence
      complementation, confirmed the interaction between Hd3a and GF14c. Functional
      analysis using either GF14c overexpression or knockout transgenic rice plants
      indicated that this interaction plays a role in the regulation of flowering.
      GF14c-overexpressing plants exhibited a delay in flowering and the knockout
      mutants displayed early flowering relative to the wild-type plants under short
      day conditions. These results suggest that GF14c acts as a negative regulator of
      flowering by interacting with Hd3a. Since the 14-3-3 protein has been shown to
      interact with FT protein in tomato and Arabidopsis, our results in rice provide
      important findings about FT signaling in plants.

PMID- 19179351
TI  - The Chlamydomonas hatching enzyme, sporangin, is expressed in specific phases of
      the cell cycle and is localized to the flagella of daughter cells within the
      sporangial cell wall.
AB  - The timely breakdown of the extracellular matrix by proteolytic enzymes is
      essential for development, morphogenesis and cell proliferation in plant and
      animal cells. Sporangin of the unicellular green alga Chlamydomonas reinhardtii
      that mediates breakdown of the sporangial cell wall to liberate the daughter
      cells after cell division is characterized as a subtilase-like serine protease.
      The sporangin gene is specifically transcribed during S/M phase in a synchronized
      vegetative cell cycle. In immunoblot analyses using a polyclonal antibody raised
      against the sporangin polypeptide, the enzyme is synthesized after mitotic cell
      division and accumulated in the daughter cells before hatching.
      Immunofluorescence analyses showed that sporangin is localized to the flagella of
      the daughter cells within the sporangial cell wall, and released into the culture
      medium. The data suggest that sporangin is released from flagella concurrently
      with the digestion of sporangial cell wall, and then the daughter cells are
      hatched from the sporangia in the Chlamydomonas vegetative cell cycle.

PMID- 19179352
TI  - Vascular NAD(P)H oxidase activation in diabetes: a double-edged sword in redox
      signalling.
AB  - Oxidative stress mediated by hyperglycaemia-induced generation of reactive oxygen
      species (ROS) contributes significantly to the development and progression of
      diabetes and related vascular complications. NAD(P)H oxidase has been implicated
      as the major source of ROS generation in the vasculature in response to high
      glucose and advanced glycation end-products. Sustained activation of NAD(P)H
      oxidase in diabetes may diminish intracellular levels of NADPH, an essential
      cofactor for endothelial NO synthase (eNOS) and several antioxidant systems.
      Recent evidence suggests that basal ROS production via NAD(P)H oxidase may
      upregulate antioxidant enzyme defenses via redox signalling. Thus, NAD(P)H
      oxidase may serve as a double-edged sword, with transient activation providing a
      feedback defense against excessive ROS generation through the activation of
      receptor tyrosine kinases and the redox-sensitive Nrf2-Keap1 signalling pathway.
      Overproduction of ROS leads to eNOS uncoupling, mitochondrial dysfunction, and
      impaired antioxidant defenses owing to depletion of intracellular NADPH. Given
      the largely negative outcome of antioxidant therapy in the treatment of diabetic
      complications, targeting the redox-sensitive transcription factor Nfr2 may
      provide an effective strategy to restore antioxidant defenses in diabetes.

PMID- 19179354
TI  - The practical use of goal attainment scaling for people with acquired brain
      injury who receive cognitive rehabilitation.
AB  - OBJECTIVE: To examine the feasibility of and clinical experiences with goal
      attainment scaling when used for the evaluation of cognitive rehabilitation in
      people with acquired brain injury. DESIGN: A prospective observational
      longitudinal study. SETTING: A 21-week cognitive rehabilitation programme and a
      cognitive programme with varying length in two different Dutch rehabilitation
      centres. SUBJECTS: Forty-eight consecutive patients with acquired brain injury
      enrolled during a 15-month period. INTERVENTIONS: Cognitive rehabilitation
      programme. MAIN MEASURE: Goal attainment scaling; the number of goals was
      counted; time to set goals was recorded; the number of different domains in which
      goals were set was counted; goal attainment scaling score was calculated at
      baseline, one week after the end of the cognitive rehabilitation programme and at
      six months follow-up; clinical experiences that could be useful for both clinical
      and research practice were recorded. RESULTS: The mean (SD) age of the patients
      was 46.1 (10.7) years; 29 (60%) were male; 186 goals were set with a mean (SD)
      number of 4 (1) goals per patient. It was possible to set at least three
      realistic goals per patient within 30 minutes. Most goals were set in the
      cognitive domain (i.e. memory and attention), followed by the behavioural domain
      (i.e. fatigue and aggression). CONCLUSION: It proved possible to set three goals
      within an acceptable time-frame, to involve patients in the goal-setting
      procedure, to set realistic goals, and to set goals within relevant domains.
      Based on clinical experiences, goal attainment scaling is less feasible for
      research when patients lack insight, or suffer from comorbidity or mood problems.

PMID- 19179355
TI  - Goal attainment scaling (GAS) in rehabilitation: a practical guide.
AB  - Goal attainment scaling is a mathematical technique for quantifying the
      achievement (or otherwise) of goals set, and it can be used in rehabilitation.
      Because several different approaches are described in the literature, this
      article presents a simple practical approach to encourage uniformity in its
      application. It outlines the process of setting goals appropriately, so that the
      achievement of each goal can be measured on a 5-point scale ranging from -2 to
      +2, and then explains a method for quantifying the outcome in a single aggregated
      goal attainment score. This method gives a numerical T-score which is normally
      distributed about a mean of 50 (if the goals are achieved precisely) with a
      standard deviation of around this mean of 10 (if the goals are overachieved or
      underachieved). If desired, the approach encompasses weighting of goals to
      reflect the opinion of the patient on the personal importance of the goal and the
      opinion of the therapist or team on the difficulty of achieving the goal. Some
      practical tips are offered, as well as a simple spreadsheet (in Microsoft Excel)
      allowing easy calculation of the T-scores.

PMID- 19179356
TI  - 'Double water exclusion': a hypothesis refining the O-ring theory for the hot
      spots at protein interfaces.
AB  - MOTIVATION: The O-ring theory reveals that the binding hot spot at a protein
      interface is surrounded by a ring of residues that are energetically less
      important than the residues in the hot spot. As this ring of residues is served
      to occlude water molecules from the hot spot, the O-ring theory is also called
      'water exclusion' hypothesis. We propose a 'double water exclusion' hypothesis to
      refine the O-ring theory by assuming the hot spot itself is water-free. To
      computationally model a water-free hot spot, we use a biclique pattern that is
      defined as two maximal groups of residues from two chains in a protein complex
      holding the property that every residue contacts with all residues in the other
      group. METHODS AND RESULTS: Given a chain pair A and B of a protein complex from
      the Protein Data Bank (PDB), we calculate the interatomic distance of all
      possible pairs of atoms between A and B. We then represent A and B as a bipartite
      graph based on these distance information. Maximal biclique subgraphs are
      subsequently identified from all of the bipartite graphs to locate biclique
      patterns at the interfaces. We address two properties of biclique patterns: a non
      redundant occurrence in PDB, and a correspondence with hot spots when the solvent
      accessible surface area (SASA) of a biclique pattern in the complex form is
      small. A total of 1293 biclique patterns are discovered which have a non
      redundant occurrence of at least five, and which each have a minimum two and four
      residues at the two sides. Through extensive queries to the HotSprint and ASEdb
      databases, we verified that biclique patterns are rich of true hot residues. Our
      algorithm and results provide a new way to identify hot spots by examining
      proteins' structural data. AVAILABILITY: The biclique mining algorithm is
      available at http://www.ntu.edu.sg/home/jyli/dwe.html. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 19179357
TI  - SECISaln, a web-based tool for the creation of structure-based alignments of
      eukaryotic SECIS elements.
AB  - SUMMARY: Selenoproteins contain the 21st amino acid selenocysteine which is
      encoded by an inframe UGA codon, usually read as a stop. In eukaryotes, its co
      translational recoding requires the presence of an RNA stem-loop structure, the
      SECIS element in the 3 untranslated region of (UTR) selenoprotein mRNAs. Despite
      little sequence conservation, SECIS elements share the same overall secondary
      structure. Until recently, the lack of a significantly high number of
      selenoprotein mRNA sequences hampered the identification of other potential
      sequence conservation. In this work, the web-based tool SECISaln provides for the
      first time an extensive structure-based sequence alignment of SECIS elements
      resulting from the well-defined secondary structure of the SECIS RNA and the
      increased size of the eukaryotic selenoproteome. We have used SECISaln to improve
      our knowledge of SECIS secondary structure and to discover novel, conserved
      nucleotide positions and we believe it will be a useful tool for the
      selenoprotein and RNA scientific communities. AVAILABILITY: SECISaln is freely
      available as a web-based tool at http://genome.crg.es/software/secisaln/.

PMID- 19179358
TI  - Life-course socioeconomic position and incidence of coronary heart disease: the
      Framingham Offspring Study.
AB  - Cumulative exposure to socioeconomic disadvantage across the life course may be
      inversely associated with coronary heart disease (CHD); the mechanisms are not
      fully clear. An objective of this study was to determine whether cumulative life
      course socioeconomic position (SEP) is associated with CHD incidence in a well
      characterized US cohort that had directly assessed childhood and adulthood
      measures of SEP and prospectively measured CHD incidence. Furthermore, analyses
      aimed to evaluate whether adjustment for CHD risk factors reduces the association
      between cumulative life-course SEP and CHD. The authors examined 1,835 subjects
      who participated in the Framingham Heart Study Offspring Cohort from 1971 through
      2003 (mean age, 35.0 years; 52.4% women). Childhood SEP was measured as father's
      education; adulthood SEP was assessed as own education and occupation. CHD
      incidence included myocardial infarction, coronary insufficiency, and coronary
      death. Cox proportional hazards analyses indicated that cumulative SEP was
      associated with incident CHD after adjustment for age and sex (hazard ratio =
      1.82, 95% confidence interval: 1.17, 2.85 for low vs. high cumulative SEP score).
      Adjustment for CHD risk factors reduced that magnitude of association (hazard
      ratio = 1.29, 95% confidence interval: 0.78, 2.13). These findings underscore the
      potential importance of CHD prevention and treatment efforts for those whose
      backgrounds include low SEP throughout life.

PMID- 19179359
TI  - Transgenerational effect of neighborhood poverty on low birth weight among
      African Americans in Cook County, Illinois.
AB  - In perinatal epidemiology, transgenerational risk factors are defined as
      conditions experienced by one generation that affect the pregnancy outcomes of
      the next generation. The authors investigated the transgenerational effect of
      neighborhood poverty on infant birth weight among African Americans. Stratified
      and multilevel logistic regression analyses were performed on an Illinois
      transgenerational data set with appended US Census income information. Singleton
      African-American infants (n = 40,648) born in 1989-1991 were considered index
      births. The mothers of index infants had been born in 1956-1976. The maternal
      grandmothers of index infants were identified. Rates of infant low birth weight
      (<2,500 g) rose as maternal grandmother's residential environment during her
      pregnancy deteriorated, independently of mother's residential environment during
      her pregnancy. In a multilevel logistic regression model that accounted for
      clustering by maternal grandmother's residential environment, the adjusted odds
      ratio (controlling for mother's age, education, prenatal care, cigarette smoking
      status, and residential environment) for infant low birth weight for maternal
      grandmother's residence in a poor neighborhood (compared with an affluent
      neighborhood) equaled 1.3 (95% confidence interval: 1.1, 1.4). This study
      suggests that maternal grandmother's exposure to neighborhood poverty during her
      pregnancy is a risk factor for infant low birth weight among African Americans.

PMID- 19179360
TI  - Induction and expression of anti-angiogenic vasohibins in the hematopoietic
      stem/progenitor cell population.
AB  - Haematopoiesis and blood vessel formation are closely associated, with several
      molecules employed by both systems. Recently, vasohibin-1 (VASH1), an endothelium
      derived negative feedback regulator of angiogenesis, has been isolated and
      characterized. VASH1 is induced by VEGF or bFGF in endothelial cells (ECs) and
      inhibits their proliferation and migration. However, there are no data on the
      induction and expression of VASH1 in haematopoietic cells (HCs). Here, we show
      that the haematopoietic stem cell (HSC) population, but not haematopoietic
      progenitors (HPs) or mature HCs from adult bone marrow (BM) constitutively
      express VASH1. However, HPs, but not HSCs, can be induced to express VASH1 after
      BM suppression by 5-FU. Knock-down of the VASH1 gene in VASH1(+) leukaemia cells
      induced cell proliferation. These results suggest a role for VASH1 in negative
      feedback regulation of HP proliferation during recovery following BM ablation.

PMID- 19179361
TI  - Molecular recognition of tryptophan tRNA by tryptophanyl-tRNA synthetase from
      Aeropyrum pernix K1.
AB  - The identity elements of transfer RNA are the molecular basis for recognition by
      each cognate aminoacyl-tRNA synthetase. In the archaea system, the tryptophan
      tRNA identity has not been determined in detail. To investigate the molecular
      recognition mechanism of tryptophan tRNA by tryptophanyl-tRNA synthetase (TrpRS)
      from the hyperthermophilic and aerobic archaeon, Aeropyrum pernix K1, various
      mutant transcripts of tryptophan tRNA prepared by an in vitro transcription
      system were examined by overexpression of A. pernix TrpRS. Substitution of the
      discriminator base, A73, impaired tryptophan incorporation activity. Changing the
      G1-C72 base pair to other base pairs also decreased the aminoacylation activity.
      Substitutions of anticodon CCA revealed that the C34 and C35 mutants dramatically
      reduced aminoacylation with tryptophan, but the A36 mutants had the same activity
      as the wild type. The results indicate that the anticodon nucleotides C34, C35,
      discriminator base A73 and G1-C72 base pair are major recognition sites for A.
      pernix TrpRS.

PMID- 19179362
TI  - Requirement of Fut8 for the expression of vascular endothelial growth factor
      receptor-2: a new mechanism for the emphysema-like changes observed in Fut8
      deficient mice.
AB  - alpha1,6-Fucosylation plays key roles in many biological functions, as evidenced
      by the study of alpha1,6-fucosyltransferase (Fut8) knockout (Fut8(-/-)) mice.
      Phenotypically, Fut8(-/-) mice exhibit emphysema-like changes in the lung, and
      severe growth retardation. Fut8(-/-) cells also show marked dysregulation of the
      TGF-beta1 receptor, EGF receptor, integrin activation and intracellular
      signalling, all of which can be rescued by reintroduction of Fut8. The results of
      the present study demonstrated that vascular endothelial growth factor receptor-2
      (VEGFR-2) expression was significantly suppressed in Fut8(-/-) mice, suggesting
      that Fut8 was required for VEGFR-2 expression. The expression of VEGFR-2 mRNA and
      protein was consistently down-regulated by knockdown of the Fut8 gene with small
      interference RNA in A549 cells, as well as in TGP49 cells, suggesting that
      suppression occurs at the level of transcription. In contrast, the expression
      level of ceramide, an inducer of cell apoptosis, was increased in the lungs of
      Fut8(-/-) mice. The terminal transferase dUTP nick end-labelling (TUNEL) assay
      was used to identify apoptotic cells. The number of TUNEL-positive septal
      epithelia and endothelia cells was significantly increased in the alveolar septa
      of lungs from Fut8(-/-) mice when in comparison with lungs from wild-type mice.
      It is well known that, in emphysema, ceramide expression can be greatly enhanced
      by blockade of the VEGFR-2. Thus, suppression of VEGFR-2 expression may provide a
      novel explanation for the emphysema-like changes in Fut8(-/-) mice.

PMID- 19179363
TI  - Feasibility of real-time three-dimensional transoesophageal echocardiography for
      guidance of percutaneous atrial septal defect closure.
AB  - AIMS: Intracardiac echocardiography (ICE) and two-dimensional transoesophageal
      echocardiography (2D TEE) are used in most centres for guiding transcatheter
      atrial septal defect (ASD) closure. ASDs have complex shapes that are not well
      characterized with 2D imaging. Real-time 3D TEE (RT3D TEE) provides en-face
      visualization of the ASD, allowing precise assessment of ASD dimensions.
      Accordingly, our aims were (i) to determine the feasibility of RT3D TEE to guide
      ASD closure and (ii) to compare ASD and balloon dimensions (BDs) using RT3D TEE
      vs. ICE and 2D TEE. METHODS AND RESULTS: Thirteen patients with ostium secundum
      ASD underwent transcatheter ASD closure. 2D TEE, RT3D TEE, and ICE images were
      acquired sequentially. RT3D TEE was feasible in all patients. Comparing RT3D TEE
      and 2D imaging, the mean difference in long-axis dimension was +0.5 mm (P= NS for
      both), and -1.4 mm in short-axis (2D TEE, P < 0.05; ICE, P = 0.06). BD was
      greater with 3D TEE vs. ICE (+0.9 mm). CONCLUSION: RT3D TEE can be used to guide
      transcatheter ASD closure with the advantages of lower cost than ICE, and ability
      to visualize en-face views of the ASD. ASD and BD as measured by RT3D TEE differ
      when compared with 2D imaging.

PMID- 19179364
TI  - Comparison of satisfaction with cancer screening at mobile van and static sites:
      National Cancer Screening Program in Korea.
AB  - OBJECTIVES: Our objectives were to evaluate participant satisfaction in the
      National Cancer Screening Program (NCSP) and to examine differences in
      satisfaction between mobile vans and static sites. METHODS: A total of 243 967
      participants who were screened by NCSP between January and May 2007 were eligible
      for the study. Of these, 3416 samples were randomly chosen and stratified by the
      type of cancer screened and screening unit. A telephone survey was conducted in
      July 2007, and 1672 participants (48.9%) were responded. The questionnaire
      included participant satisfaction with screening, screening service use and
      demographic data. Five multiple regression models were used to determine the
      relation between screening location (mobile van or static site) and each of five
      satisfaction measures (information transfer, staff interpersonal skills, privacy
      protection, physical surroundings and general satisfaction). RESULTS: Of the
      participants, 764 (45.7%) were screened at a mobile van and 908 (54.3%) at a
      static site. Relatively high scores were reported for all satisfaction measures,
      but satisfaction with screening at a mobile van was lower than that at a static
      site. Even after adjusting for potential confounders, screening at a mobile van
      was significantly associated with lower satisfaction for information transfer (P
      = 0.005), staff interpersonal skills (P = 0.025), privacy protection (P = 0.019),
      physical surroundings (P < 0.001) and general satisfaction (P < 0.001).
      CONCLUSIONS: Improving the satisfaction with and quality of mobile screening
      services is important to increase compliance and achieve the aims of the NCSP.
      Therefore, further efforts such as quality assurance or continuous monitoring are
      required.

PMID- 19179365
TI  - Acute inflammation and micrometastasis proliferation: a fissure in the
      uniformitarian facade of cancer.

PMID- 19179366
TI  - No increase in HIV or sexually transmissible infection testing following a social
      marketing campaign among men who have sex with men.
AB  - BACKGROUND: A social marketing campaign ran in 2004 in the Victoria to increase
      rates of HIV/sexually transmissible infection (STI) testing among men having sex
      with men (MSM). METHODS: To evaluate the initiative data from HIV sentinel
      surveillance, laboratory data on testing for HIV/STIs and STI/HIV testing uptake
      reported in annual surveys were analysed. RESULTS: The sentinel surveillance
      network showed no increase in the overall extent of HIV testing and no difference
      in the proportion of MSM reporting regular annual HIV testing during the campaign
      (43%) and post campaign (41%). The annual behavioural surveys showed that between
      2004 and 2006 there was no significant increase in this overall proportion of MSM
      reporting having an HIV test in the last 12 months (p = 0.96). The behavioural
      surveys also showed an increasing trend in the proportion reporting specific STI
      tests over time: anal swab (26% to 39%, p<or=0.01) and urine test (42% to 50%,
      p<or=0.01) and there was a steady increase in the amount of STI testing at the
      clinics detected through the laboratory reports: chlamydia (average increment of
      6.4 tests per month, p<0.01), gonorrhoea (6.5 tests per month, p<or=0.01) and
      syphilis (4.0 tests per month, p<or=0.01) but it began at least 2 years before
      the campaign and was not accelerated during the campaign. CONCLUSION: Based on a
      range of indicators there was no evidence that the campaign increased HIV/STI
      testing. These findings highlight the importance of evaluating public health
      campaigns to assess their impact to ensure that they are modified if no impact is
      identified.

PMID- 19179367
TI  - Tuberculosis recurrence and its associated risk factors among successfully
      treated patients.
AB  - BACKGROUND: Little is known about recurrent tuberculosis (TB) in developed
      countries. The objective of this study was to determine the probability of TB
      recurrence and the associated risk factors among cured patients in a city with
      moderate TB incidence. METHODS: A population-based retrospective longitudinal
      study was carried out in Barcelona, Spain. All patients with culture-confirmed TB
      and drug susceptibility testing were included between 1995 and 1997 and followed
      until December 2005. The authors defined recurrence as a new TB event after a
      patient was considered cured and had remained free of the disease for a minimum
      of 1 year. Kaplan-Meier and Cox regression were used in the statistical analysis.
      HRs with 95% CIs were calculated. RESULTS: Among the 681 patients studied, the
      authors observed 29 recurrences (recurrence rate 0.53/100 person-years of follow
      up). The mean incidence of TB in Barcelona from 1995 to 2005 was 36.25 cases per
      100,000 inhabitants. The incidence of recurrence was 14.6 times higher in the
      cohort than the incidence of a first TB episode in the general population. The
      factors associated with recurrence at bivariate level were being male, being an
      immigrant, being an intravenous drug user (IDU), having human immunodeficiency
      virus, smoking, being an alcoholic, being in prison, and having both pulmonary
      and extrapulmonary TB. At multivariate level, only being an immigrant (HR 3.2,
      95% CI 1.2 to 9), an IDU (HR 2.9, 95% CI 1.3 to 6.4) and male (HR 4.3, 95% CI 1.3
      to 14.6) were associated. CONCLUSION: Having TB in the past is a risk factor for
      developing TB. Social policies must be implemented in populations at risk of
      recurrence, especially in immigrants and IDUs.

PMID- 19179368
TI  - Recalibration of a Framingham risk equation for a rural population in India.
AB  - BACKGROUND: Coronary heart disease (CHD) risk estimation tools are a simple means
      of identifying those at high risk in a community and hence a potentially cost
      effective strategy for CHD prevention in resource-poor countries. Since India has
      few local data upon which to develop such a tool de novo, in this study a
      Framingham risk equation has been recalibrated to estimate CHD risks in a
      population from rural India and the sensitivity of the method to information
      resources examined. Recent surveys of this population have found high levels of
      cardiovascular risk factors, particularly metabolic risk factors and a high
      proportion of mortality due to cardiovascular diseases. METHODS: The proportion
      of a rural Indian population at high risk of CHD using three risk estimation
      equations was estimated. The first a published version of the Framingham risk
      equation, the second a recalibrated equation using local mortality surveillance
      data and local risk factor data, and the third a recalibrated equation using
      national mortality data and local risk factor data. RESULTS: The mean 10-year
      probability of CHD for adults >30 years was 10.4% (9.6% to 11.1%) for men and
      5.3% (4.9% to 5.7%) for women using the Framingham equation; 10.7% (9.9% to
      11.5%) for men and 4.2% (3.9% to 4.5%) for women using the local recalibration;
      and 18.9% (17.7% to 20.1%) for men and 8.2% (7.6% to 8.8%) for women using the
      national recalibration. CONCLUSION: These findings indicate that in India,
      equations recalibrated to summary national data are unlikely to be relevant to
      all regions of India and demonstrate the importance of local data collection to
      enable development of relevant CHD risk tools.

PMID- 19179369
TI  - Cigarette affordability trends: an update and some methodological comments.
AB  - OBJECTIVES: To calculate cigarette affordability for a number of countries using
      different techniques and data, to investigate trends since 1990 and to assess the
      appropriateness of different measures of affordability. DESIGN: Two existing
      measures were specified. Relative income price (RIP) uses per capita gross
      domestic product (GDP) as the measure of income, while "minutes of labour" is
      based on a Union Bank of Switzerland (UBS) survey of earnings. SUBJECTS: RIP
      (1990-2006) is calculated for 32 high-income and 45 low-income and middle-income
      countries. The "minutes of labour" measure is calculated for 29 high-income and
      23 low-income and middle-income countries. RESULTS: In high-income countries
      cigarettes are significantly more affordable than in low-income and middle-income
      countries, but have become less affordable since 1990. Among low-income and
      middle-income countries, cigarettes have become more affordable since 1990 and at
      an increasingly rapid rate since 2000. In 33 of 34 countries where cigarette
      affordability decreased since 1990, the real price increased. In 20 of 37
      countries where cigarettes became more affordable, real price decreased. When
      measuring affordability in low-income and middle-income countries, a broad income
      measure, such as per capita GDP, is most appropriate. For high-income countries,
      the choice of income measure is not important. CONCLUSIONS: In international
      comparisons, cigarette prices should not only be viewed in monetary terms but
      also in terms of their affordability. Fast-growing countries face greater tobacco
      control challenges since rising incomes increase the affordability of cigarettes.
      The fact that cigarettes have become increasingly affordable in a majority of low
      income and middle-income countries is a major tobacco control failure.

PMID- 19179370
TI  - Predicting the future prevalence of cigarette smoking in Australia: how low can
      we go and by when?
AB  - BACKGROUND: In Australia, smoking prevalence has declined in men since the 1950s
      and in women since the 1980s. Future smoking prevalence in Australia is predicted
      from estimates of previous and current age-specific and sex-specific cessation
      rates and smoking uptake in young people derived from national survey data on the
      prevalence of smoking between 1980 and 2007. METHODS: A dynamic forecasting model
      was used to estimate future smoking prevalence in the Australian population based
      on a continuation of these current trends in smoking uptake and cessation.
      RESULTS: The results suggest that Australia's smoking prevalence will continue to
      fall while current rates of initiation and cessation are maintained. But a
      continuation of current smoking cessation and initiation patterns will see around
      14% of adults still smoking in 2020. CONCLUSIONS: Smoking cessation rates will
      need to double for Australian smoking prevalence to reach a policy target of 10%
      by 2020.

PMID- 19179371
TI  - A rapid non-radioactive technique for measurement of repair synthesis in primary
      human fibroblasts by incorporation of ethynyl deoxyuridine (EdU).
AB  - Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder. Afflicted
      patients show extreme sun-sensitivity and skin cancer predisposition. XP is in
      most cases associated with deficient nucleotide excision repair (NER), which is
      the process responsible for removing photolesions from DNA. Measuring NER
      activity by nucleotide incorporation into repair patches, termed 'unscheduled DNA
      synthesis (UDS)', is one of the most commonly used assays for XP-diagnosis and
      NER research. We have established a rapid and accurate procedure for measuring
      UDS by replacement of thymidine with 5-ethynyl-2'-deoxyuridine (EdU). EdU
      incorporated into repair patches can be directly conjugated to fluorescent azide
      derivatives, thereby obviating the need for either radiolabeled thymidine or
      denaturation and antibody detection of incorporated bromodeoxyuridine (BrdU). We
      demonstrate that the EdU incorporation assay is compatible with conventional
      techniques such as immunofluorescent staining and labeling of cells with micro
      latex beads. Importantly, we can complete the entire UDS assay within half a day
      from preparation of the assay coverslips; this technique may prove useful as a
      method for XP diagnosis.

PMID- 19179372
TI  - Centromere sequence and dynamics in Dictyostelium discoideum.
AB  - Centromeres play a pivotal role in the life of a eukaryote cell, perform an
      essential and conserved function, but this has not led to a standard centromere
      structure. It remains currently unclear, how the centromeric function is achieved
      by widely differing structures. Since centromeres are often large and consist
      mainly of repetitive sequences they have only been analyzed in great detail in a
      handful of organisms. The genome of Dictyostelium discoideum, a valuable model
      organism, was described a few years ago but its centromere organization remained
      largely unclear. Using available sequence information we reconstructed the
      putative centromere organization in three of the six chromosomes of D.
      discoideum. They mainly consist of one type of transposons that is confined to
      centromeric regions. Centromeres are dynamic due to transposon integration, but
      an optimal centromere size seems to exist in D. discoideum. One centromere
      probably has expanded recently, whereas another underwent major rearrangements.
      In addition to insights into the centromere organization and dynamics of a
      protist eukaryote, this work also provides a starting point for the analysis of
      the evolution of centromere structures in social amoebas by comparative genomics.

PMID- 19179376
TI  - Case-control study of writer's cramp.
AB  - Task-specific focal dystonias are thought to be due to a combination of
      individual vulnerability and environmental factors. There are no case-control
      studies of risk factors for writer's cramp. We undertook a case-control study of
      104 consecutive patients and matched controls to identify risk factors for the
      condition. We collected detailed data on medical history and writing history as
      part of hobbies or occupation. Cases had a college or university degree more
      frequently than controls [OR = 4.6 (1.3-20.5), P = 0.01]. The risk of writer's
      cramp increased with the time spent writing each day (P-trend = 0.001) and was
      also associated with an abrupt increase in the writing time during the year
      before onset (OR = 5.7, 95% CI = 1.3-33.9, P = 0.02). Head trauma with loss of
      consciousness [OR = 3.5 (1.0-15.7), P = 0.05] and myopia [OR = 4.1 (1.7-12.0), P
      = 0.0009] were both associated with the condition but it was not significantly
      associated with peripheral trauma, left-handedness, constrained writing, writing
      in stressful situations or the choice of writing tool. The dose-effect
      relationship between writer's cramp and the time spent handwriting each day, and
      the additional burden of acute triggers such as an abrupt increase in the writing
      time in the year before onset, point to a disruptive phenomenon in predisposed
      subjects. Homeostatic regulation of cortical plasticity may be overwhelmed,
      resulting in dystonia.

PMID- 19179377
TI  - Differential immune cell dynamics in the CNS cause CD4+ T cell
      compartmentalization.
AB  - In the course of autoimmune CNS inflammation, inflammatory infiltrates form
      characteristic perivascular lymphocyte cuffs by mechanisms that are not yet well
      understood. Here, intravital two-photon imaging of the brain in anesthetized
      mice, with experimental autoimmune encephalomyelitis, revealed the highly dynamic
      nature of perivascular immune cells, refuting suggestions that vessel cuffs are
      the result of limited lymphocyte motility in the CNS. On the contrary, vessel
      associated lymphocyte motility is an actively promoted mechanism which can be
      blocked by CXCR4 antagonism. In vivo interference with CXCR4 in experimental
      autoimmune encephalomyelitis disrupted dynamic vessel cuffs and resulted in
      tissue-invasive migration. CXCR4-mediated perivascular lymphocyte movement along
      CNS vessels was a key feature of CD4(+) T cell subsets in contrast to random
      motility of CD8(+) T cells, indicating a dominant role of the perivascular area
      primarily for CD4(+) T cells. Our results visualize dynamic T cell motility in
      the CNS and demonstrate differential CXCR4-mediated compartmentalization of
      CD4(+) T-cell motility within the healthy and diseased CNS.

PMID- 19179378
TI  - Change in grey matter volume cannot be assumed to be due to cognitive behavioural
      therapy.

PMID- 19179379
TI  - CD8+ T-cell clones dominate brain infiltrates in Rasmussen encephalitis and
      persist in the periphery.
AB  - Rasmussen encephalitis (RE) is a rare neurological disorder of childhood
      characterized by uni-hemispheric inflammation, progressive neurological deficits
      and intractable focal epilepsy. Destruction of neurons and astrocytes by
      cytotoxic CD8 T cells has been proposed as a pathogenic mechanism underlying this
      enigmatic disorder. We tested this hypothesis by analysing the clonal composition
      and T-cell receptor (TCR) repertoire of CD4+ and CD8+ T cells using
      complementarity determining region 3 (CDR3) spectratyping from peripheral blood
      and corresponding CNS specimens. Severe perturbations of the TCR repertoire were
      found in brain infiltrates from all specimens (n = 5). Clonal expansions, as
      evidenced by peripheral blood analysis (n = 14), belonged to the CD8+ T-cell
      subset, while CD4+ cells showed normal distributions. Some of those expansions
      were analysed in the respective CNS specimens by histochemistry. The stainings
      showed Vbeta specific T cells containing the cytotoxic molecule granzyme B and
      lying in close appositions to NeuN+ neurons and GFAP+ astrocytes. Analysis of
      corresponding CNS/blood specimens revealed overlapping but also CNS-restricted
      expansions of certain TCR clonotypes suggesting expansions of T cells within the
      target organ itself. Longitudinal analysis of peripheral blood samples (n = 5)
      demonstrated dominance but also longitudinal persistence of specific CD8 T-cell
      clones over time. The Vbeta/Jbeta usage, length of the CDR3, and biochemical
      characteristics of the CDR3 amino acids suggested high similarities putatively
      related to common driving antigen(s) without shared clones. Taken together, our
      data strongly support the hypothesis of an antigen-driven MHC class-I restricted,
      CD8+ T cell-mediated attack against neurons and astrocytes in the CNS dominating
      the pathogenesis in RE.

PMID- 19179380
TI  - Activation of Ets-2 by oxidative stress induces Bcl-xL expression and accounts
      for glial survival in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease
      characterized by selective degeneration of motor neurons and glial activation.
      Cell-specific transcriptional regulation induced by oxidative stress may
      contribute to the survival and activation of astrocytes in the face of motor
      neuron death. In the present study, we demonstrate an age-dependent increase in
      Bcl-xL and Ets-2 immunoreactivity that correlates with an increase of glial
      fibrillary acidic protein (GFAP)-positive cells in the ventral horn of the spinal
      cord in both ALS transgenic mice [mutant SOD1 (G93A)] and affected humans.
      Chromatin immunoprecipitation (ChIP) analysis verified that Ets-2 preferentially
      occupies the Ets-2 binding element in the promoter of Bcl-xL in primary
      astrocytes under oxidative stress conditions as well as in G93A spinal cords. Ets
      2 small-interfering RNA down-regulated the transcriptional activity of Bcl-xL. In
      primary glial cultures, Bcl-xL overexpression and mutant SOD1 (G93A) both
      conferred resistance to oxidative stress-induced cell death. Our findings suggest
      that Ets-2 transcription factor activation of Bcl-xL gene may protect glia from
      constitutive oxidative stress that is thought to be a key mechanism contributing
      to the pathogenesis of ALS. This survival pathway may contribute to the glial
      survival and activation seen in the spinal cord of ALS patients.

PMID- 19179381
TI  - Not by the sword, but disease: Doctor Howe and General Shinseki.

PMID- 19179382
TI  - Is an increase in duodenal bicarbonate concentration after STa really enhanced
      bicarbonate ion secretion?

PMID- 19179396
TI  - Economic downturn threatens to derail millennium development goals.

PMID- 19179398
TI  - Splice-site pairing is an intrinsically high fidelity process.
AB  - The extensive alternative splicing in higher eukaryotes has initiated a debate
      whether alternative mRNA isoforms are generated by an inaccurate spliceosome or
      are the consequence of highly degenerate splice sites within the human genome.
      Here, we established a quantitative assay to evaluate the accuracy of splice-site
      pairing by determining the number of incorrect exon-skipping events made from
      constitutively spliced pre-mRNA transcripts. We demonstrate that the spliceosome
      pairs exons with an astonishingly high degree of accuracy that may be limited by
      the quality of pre-mRNAs generated by RNA pol II. The error rate of exon pairing
      is increased by the effects of the neurodegenerative disorder spinal muscular
      atrophy because of reduced levels of Survival of Motor Neuron, a master assembler
      of spliceosomal components. We conclude that all multi-intron-containing genes
      are alternatively spliced and that the reduction of SMN results in a general
      splicing defect that is mediated through alterations in the fidelity of splice
      site pairing.

PMID- 19179399
TI  - Ultrafast excited-state isomerization in phytochrome revealed by femtosecond
      stimulated Raman spectroscopy.
AB  - Photochemical interconversion between the red-absorbing (P(r)) and the far-red
      absorbing (P(fr)) forms of the photosensory protein phytochrome initiates signal
      transduction in bacteria and higher plants. The P(r)-to-P(fr) transition
      commences with a rapid Z-to-E photoisomerization at the C(15)=C(16) methine
      bridge of the bilin prosthetic group. Here, we use femtosecond stimulated Raman
      spectroscopy to probe the structural changes of the phycocyanobilin chromophore
      within phytochrome Cph1 on the ultrafast time scale. The enhanced intensity of
      the C(15)-H hydrogen out-of-plane (HOOP) mode, together with the appearance of
      red-shifted C=C stretch and N-H in-plane rocking modes within 500 fs, reveal that
      initial distortion of the C(15)=C(16) bond occurs in the electronically excited
      I* intermediate. From I*, 85% of the excited population relaxes back to P(r) in 3
      ps, whereas the rest goes on to the Lumi-R photoproduct consistent with the 15%
      photochemical quantum yield. The C(15)-H HOOP and skeletal modes evolve to a Lumi
      R-like pattern after 3 ps, thereby indicating that the C(15)=C(16) Z-to-E
      isomerization occurs on the excited-state surface.

PMID- 19179400
TI  - The carboxy-terminal domain of complexin I stimulates liposome fusion.
AB  - Regulated exocytosis requires tight coupling of the membrane fusion machinery to
      a triggering signal and a fast response time. Complexins are part of this
      regulation and, together with synaptotagmins, control calcium-dependent
      exocytosis. Stimulatory and inhibitory functions have been reported for
      complexins. To test if complexins directly affect membrane fusion, we analyzed
      the 4 known mammalian complexin isoforms in a reconstituted fusion assay. In
      contrast to complexin III (CpxIII) and CpxIV, CpxI and CpxII stimulated soluble N
      ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-pin assembly
      and membrane fusion. This stimulatory effect required a preincubation at low
      temperature and was specific for neuronal t-SNAREs. Stimulation of membrane
      fusion was lost when the carboxy-terminal domain of CpxI was deleted or serine
      115, a putative phosphorylation site, was mutated. Transfer of the carboxy
      terminal domain of CpxI to CpxIII resulted in a stimulatory CpxIII-I chimera.
      Thus, the carboxy-terminal domains of CpxI and CpxII promote the fusion of high
      curvature liposomes.

PMID- 19179401
TI  - A combination of unusual transcription factors binds cooperatively to control
      Myxococcus xanthus developmental gene expression.
AB  - Myxococcus xanthus is a bacterium that undergoes multicellular development
      requiring coordinate regulation of multiple signaling pathways. One pathway
      governs aggregation and sporulation of some cells in a starving population and
      requires C-signaling, whereas another pathway causes programmed cell death and
      requires the MazF toxin. In response to starvation, the levels of the
      bifunctional transcription factor/antitoxin MrpC and its related proteolytic
      fragment MrpC2 are increased, inhibiting the cell death pathway via direct
      interaction of MrpC with MazF. Herein, we demonstrate that MrpC2 plays a direct
      role in the transcriptional response to C-signaling. We show that MrpC2 binds to
      sequences upstream of the C-signal-dependent fmgA promoter. These sequences are
      present in other C-signal-dependent promoter regions, indicating a general role
      for MrpC2 in developmental gene regulation. Association of MrpC and/or MrpC2 with
      the fmgA promoter region in vivo requires FruA, a protein that is similar to
      response regulators of 2-component signal transduction systems, but may not be
      phosphorylated. DNA binding studies showed that this association likely involves
      an unusual mechanism for a response regulator in which FruA and MrpC2 bind
      cooperatively to adjacent sites upstream of the fmgA promoter. We propose that
      this unusual mechanism of combinatorial control allows coordination of
      morphogenetic C-signaling with starvation signaling and cell death, determining
      spatiotemporal gene expression and cell fate.

PMID- 19179403
TI  - Canopy nitrogen and albedo from remote sensing: what exactly are we seeing?

PMID- 19179402
TI  - R-Spondin1 protects mice from chemotherapy or radiation-induced oral mucositis
      through the canonical Wnt/beta-catenin pathway.
AB  - R-Spondin1 (RSpo1) is a novel secreted protein that augments canonical Wnt/beta
      catenin signaling. We injected recombinant RSpo1 protein into transgenic Wnt
      reporter TOPGAL mice and have identified the oral mucosa as a target tissue for
      RSpo1. Administration of RSpo1 into normal mice triggered nuclear translocation
      of beta-catenin and resulted in increased basal layer cellularity, thickened
      mucosa, and elevated epithelial cell proliferation in tongue. We herein evaluated
      the therapeutic potential of RSpo1 in treating chemotherapy or radiotherapy
      induced oral mucositis in several mouse models. Prophylactic treatment with RSpo1
      dose-dependently overcame the reduction of basal layer epithelial cellularity,
      mucosal thickness, and epithelial cell proliferation in tongues of mice exposed
      to whole-body irradiation. RSpo1 administration also substantially alleviated
      tongue mucositis in the oral cavity of mice receiving concomitant 5-fluorouracil
      and x-ray radiation. Furthermore, RSpo1 significantly reduced the extent of
      tongue ulceration in mice receiving a single fraction, high dose head-only
      radiation in a dose-dependent manner. Moreover, combined therapy of RSpo1 and
      keratinocyte growth factor resulted in complete healing of tongue ulcers in mice
      subjected to snout-only irradiation. In conclusion, our results demonstrate RSpo1
      to be a potent therapeutic agent for oral mucositis by enhancing basal layer
      epithelial regeneration and accelerating mucosal repair through up-regulation of
      Wnt/beta-catenin pathway.

PMID- 19179404
TI  - Diffusion tensor tractography should be used with caution.

PMID- 19179405
TI  - Patient-rated changes in fatigue over a 12-month period predict poor outcome in
      chronic heart failure.
AB  - AIMS: Little is known about the factors that are associated with changes in
      fatigue in chronic heart failure (CHF). Moreover, it is unclear whether these
      changes have prognostic impact. The aim of this study was to examine these
      issues. METHODS AND RESULTS: Three hundred and eighty-seven CHF patients were
      assessed twice (at baseline and at 12-month follow-up) for exertion and general
      fatigue. Regression models were developed to assess whether baseline
      characteristics predicted changes in fatigue and to assess the effect of changes
      in fatigue on cardiac events occurring beyond 12-months of follow-up. An increase
      in exertion fatigue over a 12-month period was predicted by higher left
      ventricular ejection fraction (P = 0.02) and cognitive-affective depressive
      symptoms (P = 0.03) at baseline, and not having a biventricular pacemaker shortly
      after baseline (P = 0.02), whereas an increase in general fatigue was only
      predicted by cognitive-affective depressive symptoms (P = 0.002). One hundred and
      forty-three patients (37%) experienced an event (readmitted, 117; death, 26). An
      increase in exertion fatigue was associated with a near two-fold increased risk
      of events beyond 12-months of follow-up (hazard ratio = 1.78; 95% confidence
      interval 1.18-2.68, P = 0.006), while controlling for standard cardiac risk
      factors. CONCLUSION: Baseline clinical and psychosocial factors predicted changes
      in fatigue. Increased exertion fatigue independently predicted an increased risk
      of cardiac re-admission or death.

PMID- 19179406
TI  - The prognostic value of repeated measurement of N-terminal pro-B-type natriuretic
      peptide in patients with chronic heart failure due to left ventricular systolic
      dysfunction.
AB  - AIMS: Decreased N-terminal pro-B-type natriuretic peptide (NT-proBNP) during
      treatment of chronic heart failure (CHF) is associated with improved prognosis.
      However, there is lack of data from community-based HF programmes. We
      hypothesized that plasma levels of NT-proBNP, measured after optimization of
      pharmacotherapy in patients with CHF, may provide independent prognostic
      information when compared with baseline values and conventional prognostic
      markers. METHODS AND RESULTS: N-terminal pro-B-type natriuretic peptide was
      measured in 354 patients with CHF and left ventricular ejection fraction <45%,
      who had recently been enrolled in a community-based HF programme. Patients
      underwent a 6 min walk test and clinical, echocardiographic and laboratory
      examinations. Pharmacotherapy was optimized; 318 patients survived until the
      second examination and measurement of NT-proBNP, which was performed between the
      4th and 6th month of follow-up. During a median follow-up of 38.8 months, 125
      patients died. Follow-up log NT-proBNP was a better predictor of death than
      either baseline log NT-proBNP or change in NT-proBNP (chi(2): 46.5 vs. 30.4 and
      12.5, all P < 0.001). N-terminal pro-B-type natriuretic peptide was consistently
      the strongest independent prognostic marker at predicting death or unplanned
      cardiovascular hospitalizations after baseline or follow-up assessment.
      CONCLUSION: The measurement of NT-proBNP after optimization of pharmacotherapy
      provides stronger prognostic information than either the baseline value, the
      change in NT-proBNP, or other conventional methods of assessment.

PMID- 19179407
TI  - A case for clarity in causation? Bailey v. Ministry of Defence and another.

PMID- 19179408
TI  - Control of homologous chromosome division in the mammalian oocyte.
AB  - Homologous chromosomes are segregated during the first meiotic division (meiosis
      I). Unfortunately, human oocytes are particularly susceptible to mis-segregation
      errors, so generating aneuploid, often non-viable, embryos. Here we review the
      cell biology of meiosis I and how homolog disjunction is regulated for mammalian
      oocytes. We focus on the activity of the anaphase-promoting complex/cyclosome
      (APC/C), which is responsible for timely degradation of the cohesin component,
      REC8 and the cyclin B regulatory subunit of maturation-promoting factor, both
      essential steps for meiosis I completion. In particular, we examine the role
      played by the spindle assembly checkpoint in controlling the APC/C activity, and
      in so doing ensuring accurate disjunction of homologs.

PMID- 19179409
TI  - Do temporal artery duplex ultrasound findings correlate with ophthalmic
      complications in giant cell arteritis?
AB  - OBJECTIVE: Ophthalmic complications are common in acute GCA. Do temporal artery
      ultrasound and clinical parameters correlate with the occurrence and severity of
      ophthalmic complications? METHODS: The results of temporal artery ultrasound
      examinations are compared with the occurrence of anterior ischaemic optic
      neuropathy (AION), central retinal artery occlusion (CRAO), branch retinal artery
      occlusion (BRAO), diplopia and amaurosis fugax in 222 consecutive patients with
      newly diagnosed, active GCA. RESULTS: Temporal artery ultrasound displayed
      vasculitic wall swelling (halo), stenoses and/or acute occlusions in 84% (58% in
      67 large-vessel GCA patients and 95% in 155 patients without proximal arm
      vasculitis). Ophthalmic complications occurred in 64 (29%), AION in 30 (14%),
      CRAO in 7 (3%), BRAO in 2 (1%), amaurosis fugax in 16 (7%) and diplopia in 9
      patients (4%). Ophthalmic complications were insignificantly more common if
      temporal artery ultrasound was positive (31 vs 17%; P = 0.11) as a greater number
      of patients without arm vasculitis showed eye involvement (34 vs 18%; P = 0.02).
      The number of pathological temporal artery segments, presence of stenoses or
      bilateral findings did not correlate with ophthalmic complications. Age >or= 72
      yrs at diagnosis correlated with a higher incidence of ophthalmic complications.
      CONCLUSION: Ophthalmic complications occurred less frequently if proximal arm
      vasculitis was present. Findings of temporal artery ultrasound did not correlate
      with eye complications.

PMID- 19179410
TI  - Global nephrology guidelines: a first small step in the right direction.

PMID- 19179411
TI  - Rituximab and mycophenolate mofetil for relapsing proliferative lupus nephritis:
      a long-term prospective study.
AB  - BACKGROUND: Subsequent to cyclophosphamide-based induction therapy of lupus
      nephritis, and despite maintenance chronic immunosuppressive treatment, many
      patients experience relapses. METHODS: This prospective, observational study
      included 10 women with biopsy-proven relapse of proliferative lupus nephritis
      occurring during maintenance with mycophenolate mofetil (MMF) or azathioprine.
      The long-term outcome after a single course of the B-cell depleting anti-CD20
      antibody rituximab (4 weekly infusions of 375 mg/m(2)), combined with daily MMF
      (2 g) and prednisolone (0.5 mg/ kg/day for 4 weeks, tapered thereafter) is
      presented. RESULTS: While renal function was not severely impaired at baseline,
      partial remission (>50% improvement in all abnormal renal parameters) was
      achieved in eight patients at a median of 3.5 months. In seven patients, with 24
      h urinary protein of 2.5 +/- 1.1 g (mean +/- SD), complete remission, associated
      with increases in serum complement levels and decreases in anti-dsDNA titres, was
      subsequently established (normal serum creatinine/albumin levels, inactive urine
      sediment and 24-h urinary protein <0.5 g). Complete nephritis remission was
      sustained at the follow-up end (median of 38 months) in six patients. Combination
      treatment was well tolerated. CONCLUSIONS: The efficacy of this low-toxicity
      combination was particularly evident in patients with subnephrotic proteinuria
      due to proliferative lupus nephritis relapse. Controlled trials to define the
      role of rituximab/MMF in this condition are warranted.

PMID- 19179412
TI  - Bisphosphonates in oncology: rising stars or fallen heroes.
AB  - The introduction of bisphosphonates in oncology has dramatically changed the
      management of patients with metastatic bone disease. In this manuscript, we
      thoroughly scrutinize the available body of clinical trials supporting the use of
      bisphosphonates in this setting and review new and ongoing research.
      Additionally, we summarize the data showing the benefits of bisphosphonate use in
      the prevention of treatment-induced bone loss and the intriguing emerging
      evidence on the antitumor potential of some of these agents when used in the
      adjuvant setting. Finally, we address the need for a careful consideration of
      potential benefits of bisphosphonate therapy and the risk for osteonecrosis of
      the jaw, a recently recognized late-toxicity of their use.

PMID- 19179413
TI  - Multiple mechanisms contribute to the robust rapid gamma interferon response by
      CD8+ T cells during Listeria monocytogenes infection.
AB  - A subset of CD8+ T cells can rapidly secrete gamma interferon (IFN-gamma) in an
      antigen-independent and interleukin-12 (IL-12)- and IL-18-dependent manner within
      16 h of infection with the intracellular bacterial pathogen Listeria
      monocytogenes. This rapid IFN-gamma response is robust enough to be detected
      directly ex vivo and is not observed following infection with intracellular
      bacterial pathogens that remain sequestered within host cell vacuoles. We
      demonstrate here that three distinct pathways can lead to rapid secretion of IFN
      gamma by CD8+ T cells during L. monocytogenes infection: (i) a direct cytokine
      inducing activity encoded by the cholesterol-dependent cytolysin (CDC)
      listeriolysin O (LLO) acts within the infected cell, (ii) the pore-forming
      activity of LLO promotes cytosolic localization of bacterial products that
      trigger cytosol-specific signaling pathways, and (iii) the sustained presence of
      high concentrations of bacterial products can exogenously trigger cytokine
      production. Although it has been suggested that CDC protein toxins may act as
      Toll-like receptor 4 (TLR4) agonists to trigger proinflammatory cytokine
      secretion, we show in this report that TLR4 signaling is not required to induce a
      maximal rapid IFN-gamma response by CD8+ T cells. The results presented here
      indicate that multiple mechanisms contribute to the induction of rapid IFN-gamma
      secretion by CD8+ T cells during Listeria infection and that care must be taken
      when interpreting the results of in vitro assays, since the contribution of each
      pathway can vary depending on how the assay is performed.

PMID- 19179414
TI  - Helicobacter pylori-induced interleukin-12 p40 expression.
AB  - Interleukin-12 (IL-12) is a heterodimeric cytokine produced by antigen-presenting
      cells that promotes the development of T-helper lymphocyte 1 (Th1). Chronic
      gastritis induced by Helicobacter pylori is considered a Th1-mediated process. IL
      12 levels in gastric biopsy samples of H. pylori-infected patients are higher
      than in those of uninfected individuals, but the cellular source of IL-12 remains
      elusive. IL-12 staining was detected in mucosal epithelial cells, lymphocytes,
      and macrophages in specimens of patients with H. pylori-positive gastritis.
      Therefore, we investigated IL-12 p40 mRNA induction by H. pylori in gastric
      epithelial cells and T cells. Although cag pathogenicity island (PAI)-positive H.
      pylori induced IL-12 p40 mRNA expression, an isogenic mutant of the cag PAI
      failed to induce it in both cell types. Supernatants from H. pylori cultures and
      H. pylori VacA induced IL-12 p40 mRNA expression in T cells but not in epithelial
      cells. The activation of the IL-12 p40 promoter by H. pylori was mediated through
      NF-kappaB. The transfection of IkappaB kinase and NF-kappaB-inducing kinase
      dominant-negative mutants inhibited H. pylori-induced IL-12 p40 activation.
      Inhibitors of NF-kappaB, phosphatidylinositol 3-kinase, p38 mitogen-activated
      protein kinase, and Hsp90 suppressed H. pylori- and VacA-induced IL-12 p40 mRNA
      expression. The results indicate that H. pylori induces IL-12 p40 expression by
      the activation of NF-kappaB, phosphatidylinositol 3-kinase, and p38 mitogen
      activated protein kinase. Hsp90 is also a crucial regulator of H. pylori-induced
      IL-12 p40 expression. In addition to the cag PAI, VacA might be relevant in the
      induction of IL-12 expression and a Th1-polarized response only in T cells.

PMID- 19179415
TI  - Protection from pneumonic infection with burkholderia species by inhalational
      immunotherapy.
AB  - Burkholderia mallei and B. pseudomallei are important human pathogens and cause
      the diseases glanders and melioidosis, respectively. Both organisms are highly
      infectious when inhaled and are inherently resistant to many antimicrobials, thus
      making it difficult to treat pneumonic Burkholderia infections. We investigated
      whether it was possible to achieve rapid protection against inhaled Burkholderia
      infection by using inhaled immunotherapy. For this purpose, cationic liposome DNA
      complexes (CLDC), which are potent activators of innate immunity, were used to
      elicit the activation of pulmonary innate immune responses. We found that mucosal
      CLDC administration before or shortly after bacterial challenge could generate
      complete or nearly complete protection from inhalational challenge with 100%
      lethal doses of B. mallei and B. pseudomallei. Protection was found to be
      dependent on the CLDC-mediated induction of gamma interferon responses in lung
      tissues and was partially dependent on the activation of NK cells. However, CLDC
      mediated protection was not dependent on the induction of inducible nitric oxide
      synthase, as assessed by depletion studies. We concluded that the potent local
      activation of innate immune responses in the lung could be used to elicit rapid
      and nonspecific protection from aerosol exposure to both B. mallei and B.
      pseudomallei.

PMID- 19179416
TI  - Monoclonal antibodies to heat shock protein 60 alter the pathogenesis of
      Histoplasma capsulatum.
AB  - Heat shock proteins with molecular masses of approximately 60 kDa (Hsp60) are
      widely distributed in nature and are highly conserved immunogenic molecules that
      can function as molecular chaperones and enhance cellular survival under
      physiological stress conditions. The fungus Histoplasma capsulatum displays an
      Hsp60 on its cell surface that is a key target of the cellular immune response
      during histoplasmosis, and immunization with this protein is protective. However,
      the role of humoral responses to Hsp60 has not been fully elucidated. We
      generated immunoglobulin G (IgG) isotype monoclonal antibodies (MAbs) to H.
      capsulatum Hsp60. IgG1 and IgG2a MAbs significantly prolonged the survival of
      mice infected with H. capsulatum. An IgG2b MAb was not protective. The protective
      MAbs reduced intracellular fungal survival and increased phagolysosomal fusion of
      macrophages in vitro. Histological examination of infected mice showed that
      protective MAbs reduced the fungal burden and organ damage. Organs of infected
      animals treated with protective MAbs had significantly increased levels of
      interleukin-2 (IL-2), IL-12, and tumor necrosis factor alpha and decreased levels
      of IL-4 and IL-10. Hence, IgG1 and IgG2a MAbs to Hsp60 can modify H. capsulatum
      pathogenesis in part by altering the intracellular fate of the fungus and
      inducing the production of Th1-associated cytokines.

PMID- 19179417
TI  - Toll-like receptor 2 deficiency is associated with enhanced severity of group B
      streptococcal disease.
AB  - Group B streptococcus (GBS) has been recognized as an ever-growing cause of
      serious invasive infections in nonpregnant adults, in particular, in association
      with severe underlying diseases. The most common manifestations include primary
      bacteremia, urinary tract infections, pneumonia, meningitis, peritonitis, and
      osteoarticular infections. Toll-like receptor-2 (TLR2) mediates host responses to
      gram-positive bacteria. TLR2 function was investigated in murine GBS-induced
      sepsis and arthritis in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice. Mice
      were infected with different doses of GBS (10(7), 5 x 10(6), or 10(6) CFU per
      mouse). Mortality, appearance of arthritis, GBS growth in the organs, and local
      and systemic cytokine and chemokine production were examined. TLR2(-/-) mice
      showed earlier and higher mortality rates and increased incidence and severity of
      arthritis than wt mice at all the infecting doses employed. Histopathological
      analysis of the joints confirmed clinical observations. TLR2(-/-) mice exhibited
      a higher microbial load in blood, kidneys, and joints than wt animals. In vitro
      experiments performed with peritoneal polymorphonuclear cells and macrophages
      showed a significantly lower bactericidal ability of cells from TLR2(-/-) mice.
      Increased systemic and local levels of interleukin-1beta (IL-1beta), IL-6, tumor
      necrosis factor alpha, macrophage inflammatory protein-1alpha (MIP-1alpha), and
      MIP-2 accompanied the more severe development of sepsis and arthritis in TLR2(-/
      ) mice. In conclusion, the lack of TLR2 was associated with an impaired host
      resistance to GBS infection, likely due to a diminished bacterial clearing and a
      consequent enhanced inflammatory response.

PMID- 19179418
TI  - Caspase-1 mediates resistance in murine melioidosis.
AB  - The gram-negative rod Burkholderia pseudomallei is the causative agent of
      melioidosis, a potentially fatal disease which is endemic in tropical and
      subtropical areas. The bacterium multiplies intracellularly within the cytosol,
      induces the formation of actin tails, and can spread directly from cell to cell.
      Recently, it has been shown that B. pseudomallei can induce caspase-1-dependent
      cell death in macrophages. The aim of the present study was to further elucidate
      the role of caspase-1 during B. pseudomallei infection. In vivo experiments with
      caspase-1(-/-) mice revealed a high susceptibility to B. pseudomallei challenge.
      This phenotype was associated with a significantly higher bacterial burden 2 days
      after infection and decreased gamma interferon (IFN-gamma) and interleukin-18
      cytokine levels 24 h after infection compared to control animals. caspase-1(-/-)
      bone marrow-derived macrophages (BMM) exhibited strong caspase-3 expression and
      reduced cell damage compared to wild-type (WT) cells during early B. pseudomallei
      infection, indicating "classical" apoptosis, whereas WT BMM showed signs of rapid
      caspase-1-dependent cell death. Moreover, we found that caspase-1(-/-) BMM had a
      strongly increased bacterial burden compared to WT cells 3 h after infection
      under conditions where no difference in cell death could be observed between both
      cell populations at this time point. We therefore suggest that caspase-1
      dependent rapid cell death might contribute to resistance by reducing the
      intracellular niche for B. pseudomallei, but, in addition, caspase-1 might also
      have a role in controlling intracellular replication of B. pseudomallei in
      macrophages. Moreover, caspase-1-dependent IFN-gamma production is likely to
      contribute to resistance in murine melioidosis.

PMID- 19179419
TI  - Antimicrobial effects of interferon-inducible CXC chemokines against Bacillus
      anthracis spores and bacilli.
AB  - Based on previous studies showing that host chemokines exert antimicrobial
      activities against bacteria, we sought to determine whether the interferon
      inducible Glu-Leu-Arg-negative CXC chemokines CXCL9, CXCL10, and CXCL11 exhibit
      antimicrobial activities against Bacillus anthracis. In vitro analysis
      demonstrated that all three CXC chemokines exerted direct antimicrobial effects
      against B. anthracis spores and bacilli including marked reductions in spore and
      bacillus viability as determined using a fluorometric assay of bacterial
      viability and CFU determinations. Electron microscopy studies revealed that
      CXCL10-treated spores failed to undergo germination as judged by an absence of
      cytological changes in spore structure that occur during the process of
      germination. Immunogold labeling of CXCL10-treated spores demonstrated that the
      chemokine was located internal to the exosporium in association primarily with
      the spore coat and its interface with the cortex. To begin examining the
      potential biological relevance of chemokine-mediated antimicrobial activity, we
      used a murine model of inhalational anthrax. Upon spore challenge, the lungs of
      C57BL/6 mice (resistant to inhalational B. anthracis infection) had significantly
      higher levels of CXCL9, CXCL10, and CXCL11 than did the lungs of A/J mice (highly
      susceptible to infection). Increased CXC chemokine levels were associated with
      significantly reduced levels of spore germination within the lungs as determined
      by in vivo imaging. Taken together, our data demonstrate a novel antimicrobial
      role for host chemokines against B. anthracis that provides unique insight into
      host defense against inhalational anthrax; these data also support the notion for
      an innovative approach in treating B. anthracis infection as well as infections
      caused by other spore-forming organisms.

PMID- 19179421
TI  - The CsgA and Lpp proteins of an Escherichia coli O157:H7 strain affect HEp-2 cell
      invasion, motility, and biofilm formation.
AB  - In Escherichia coli O157:H7 strain ATCC 43895, a guanine-to-thymine transversion
      in the csgD promoter created strain 43895OR. Strain 43895OR produces an abundant
      extracellular matrix rich in curli fibers, forms biofilms on solid surfaces,
      invades cultured epithelial cells, and is more virulent in mice than strain
      43895. In this study we compared the formic acid-soluble proteins expressed by
      strains 43895OR and 43895 using one-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis and identified two differentially
      expressed proteins. A 17-kDa protein unique to strain 43895OR was identified from
      matrix-assisted laser desorption ionization-time of flight analysis combined with
      mass spectrometry (MS) and tandem MS (MS/MS) as the curli subunit encoded by
      csgA. A <10-kDa protein, more highly expressed in strain 43895, was identified as
      the Lpp lipoprotein. Mutants of strain 43895OR with disruption of lpp, csgA, or
      both lpp and csgA were created and tested for changes in phenotype and function.
      The results of this study show that both Lpp and CsgA contribute to the observed
      colony morphology, Congo red binding, motility, and biofilm formation. We also
      show that both CsgA and Lpp are required by strain 43895OR for the invasion of
      cultured HEp-2 cells. These studies suggest that in strain 43895OR, the murein
      lipoprotein Lpp indirectly regulates CsgA expression through the CpxAR system by
      a posttranscriptional mechanism.

PMID- 19179420
TI  - Anthrax protective antigen delivered by Salmonella enterica serovar Typhi Ty21a
      protects mice from a lethal anthrax spore challenge.
AB  - Bacillus anthracis, the etiological agent of anthrax disease, is a proven weapon
      of bioterrorism. Currently, the only licensed vaccine against anthrax in the
      United States is AVA Biothrax, which, although efficacious, suffers from several
      limitations. This vaccine requires six injectable doses over 18 months to
      stimulate protective immunity, requires a cold chain for storage, and in many
      cases has been associated with adverse effects. In this study, we modified the B.
      anthracis protective antigen (PA) gene for optimal expression and stability,
      linked it to an inducible promoter for maximal expression in the host, and fused
      it to the secretion signal of the Escherichia coli alpha-hemolysin protein (HlyA)
      on a low-copy-number plasmid. This plasmid was introduced into the licensed
      typhoid vaccine strain, Salmonella enterica serovar Typhi strain Ty21a, and was
      found to be genetically stable. Immunization of mice with three vaccine doses
      elicited a strong PA-specific serum immunoglobulin G response with a geometric
      mean titer of 30,000 (range, 5,800 to 157,000) and lethal-toxin-neutralizing
      titers greater than 16,000. Vaccinated mice demonstrated 100% protection against
      a lethal intranasal challenge with aerosolized spores of B. anthracis 7702. The
      ultimate goal is a temperature-stable, safe, oral human vaccine against anthrax
      infection that can be self-administered in a few doses over a short period of
      time.

PMID- 19179422
TI  - Trypanosoma cruzi promotes neuronal and glial cell survival through the
      neurotrophic receptor TrkC.
AB  - Trypanosoma cruzi, the agent of Chagas' disease, promotes neuron survival through
      receptor tyrosine kinase TrkA and glycosylphosphatidylinositol-anchored glial
      cell-derived family ligand receptors (GFRalpha). However, these receptors are
      expressed by only a subset of neurons and at low levels or not at all in glial
      cells. Thus, T. cruzi might exploit an additional neurotrophic receptor(s) to
      maximize host-parasite equilibrium in the nervous system. We show here that T.
      cruzi binds TrkC, a neurotrophic receptor expressed by glial cells and many types
      of neurons, and that the binding is specifically inhibited by neurotrophin-3, the
      natural TrkC ligand. Coimmunoprecipitation and competition assays show that the
      trans-sialidase/parasite-derived neurotrophic factor (PDNF), previously
      identified as a TrkA ligand, mediates the T. cruzi-TrkC interaction. PDNF
      promotes TrkC-dependent mitogen-activated protein kinase signaling, neurite
      outgrowth, and survival of genetically engineered PC12 neuronal cells and glial
      Schwann cells in a TrkC-dependent manner. Thus, TrkC is a new neurotrophic
      receptor that T. cruzi engages to promote the survival of neuronal and glial
      cells. The results raise the possibility that T. cruzi recognition of TrkC
      underlies regenerative events in nervous tissues of patients with Chagas'
      disease.

PMID- 19179423
TI  - Risk analysis of severe myelotoxicity with temozolomide: the effects of clinical
      and genetic factors.
AB  - A benefit of temozolomide (TMZ) is that myelotoxicity is uncommon. Recently,
      several small series have reported significant myelotoxicity resulting in
      treatment delays or death. The ability to predict risk of myelotoxicity may
      influence patient care. We retrospectively reviewed 680 malignant glioma patients
      and developed a clinical risk formula for myelotoxicity for each gender by
      logistic regression. The variables that remained were assigned a score of 1 and
      added together for a final risk score. Women experienced more myelotoxicity than
      did men (p = 0.015). For males, risk factors included body surface area (BSA) >
      or = 2 m(2) (odds ratio [OR] = 2.712, p = 0.04), not on steroids (OR = 2.214, p =
      0.06), and on bowel medication (OR = 3.955, p = 0.008). For females, final
      factors included no prior chemotherapy (OR = 3.727, p = 0.001), creatinine > or =
      1 mg/dl (OR = 6.08, p = 0.002), platelets < 270,000/mm(3) (OR = 2.438, p = 0.03),
      BSA < 2 m(2) (OR = 4.178, p = 0.04), not on medication for gastroesophageal
      reflux disease (OR = 2.942, p = 0.01), and on analgesics (OR = 2.169, p = 0.05).
      Age was included because of observable trends. Risk of developing myelotoxicity
      ranged from 0% to 33% (male) and from 0% to 100% (females). Polymorphisms in NQO1
      (NAD(P)H dehydrogenase, quinone 1), MGMT (O(6)-methylguanine-DNA
      methyltransferase), and GSTP1 (glutathione S-transferase pi 1) were related to
      risk of developing myelotoxicity in a subset of patients. Myelotoxicity with TMZ
      is a significant clinical issue for those at risk. Use of a clinical model to
      predict risk and evaluation of identified genetic polymorphisms related to
      myelotoxicity may allow for individualized dosing, optimizing patient management.

PMID- 19179424
TI  - Analysis of microsatellite instability in medulloblastoma.
AB  - Medulloblastoma is the most common malignant brain tumor in children. The
      presence of microsatellite instability (MSI) in brain tumors, particularly
      medulloblastomas, has not been properly addressed. The aim of the present study
      was to evaluate the role of MSI in medulloblastoma carcinogenesis. MSI status was
      determined in 36 patients using a pentaplex PCR of quasimonomorphic markers
      (NR27, NR21, NR24, BAT25, and BAT26). Methylation status of mismatch repair (MMR)
      genes was achieved by methylation-specific multiplex ligation-dependent probe
      amplification (MLPA). In addition, MutS homolog 6 (MSH6) expression was
      determined by immunohistochemistry. Mutations of 10 MSI target genes (TCF4,
      XRCC2, MBD4, MRE11, ATR, MSH3, TGFBR2, RAD50, MSH6, and BAX) were studied by
      pentaplex PCR followed by analysis with GeneScan 3.7 software. Mutation analysis
      of hotspot regions of beta-catenin (CTNNB1) and BRAF (v-raf murine sarcoma viral
      oncogene homolog B1) oncogenes was performed by PCR single-strand conformation
      polymorphism analysis followed by direct sequencing. Among the 36 tumors, we
      found four (11%) cases with instability, one with high MSI and three with low
      MSI. Methylation analysis of MMR genes in cases presenting shifts on the MSI
      markers revealed mild hypermethylation of MSH6 in 75% of cases, yet MSH6 was
      expressed in all the tumors. The MSI target genes MBD4 (methyl-CpG binding domain
      protein 4) and MRE11 (meiotic recombination 11 homolog A) were mutated in two
      different tumors. No CTNNB1 or BRAF mutations were found. This study is the most
      comprehensive analysis of MSI in medulloblastomas to date. We observed the
      presence of MSI together with mutations of MSI target genes in a small fraction
      of cases, suggesting a new genetic pathway for a role in medulloblastoma
      development.

PMID- 19179426
TI  - MR angiography of a 1-year-old girl with semilobar holoprosencephaly.

PMID- 19179425
TI  - Radiation-induced meningiomas: a shadow in the success story of childhood
      leukemia.
AB  - While the prognosis of acute childhood leukemia has improved, long-term survivors
      are increasingly experiencing late effects of the treatment. Cranially irradiated
      survivors are predisposed to the development of CNS tumors. Our aim was to
      describe the incidence of secondary brain tumors and to define the significance
      of treatment-related risk factors and host characteristics in a cohort of
      childhood leukemia survivors. Our cohort consisted of 60 consecutive cranially
      irradiated adult survivors of childhood leukemia treated in Oulu University
      Hospital (Oulu, Finland); MRI of the brain was performed on 49. The sites of the
      tumors, their histology, and details of the leukemia treatment were determined.
      Of the 49 patients, 11 (22%) 1-8 years of age at the time of diagnosis developed
      meningioma later in life, while no other brain tumors were seen. In this cohort,
      the development of meningioma seemed to show undisputable linkage with long
      latency periods (mean, 25 years; range, 14-34 years) and an increasing incidence
      20 years after the treatment (47%). Three patients had multiple meningiomas, two
      had recurrent disease, and one had an atypical meningioma. Age at the time of
      irradiation, gender, or cumulative doses of chemotherapeutic agents showed no
      significant association with the development of meningiomas. The high incidence
      of meningiomas in this study was associated with long follow-up periods. Although
      the cohort is small, it seems probable that the increasing incidence of
      meningioma will shadow the future of cranially irradiated leukemia survivors.
      Systematic brain imaging after the treatment is therefore justifiable.

PMID- 19179427
TI  - Cerebral blood volume measurements by perfusion-weighted MR imaging in gliomas:
      ready for prime time in predicting short-term outcome and recurrent disease?
AB  - BACKGROUND AND PURPOSE: Current classification and grading of primary brain
      tumors has significant limitations. Our aim was to determine whether the relative
      cerebral volume (rCBV) measurements in gliomas may serve as an adjunct to
      histopathologic grading, with a hypothesis that rCBV values are more accurate in
      predicting 1-year survival and recurrence. MATERIALS AND METHODS: Thirty-four
      patients with gliomas (WHO grade I-IV, 27 astrocytomas, 7 tumors with
      oligodendroglial components) underwent contrast-enhanced MR rCBV measurements
      before treatment. The region of interest and the single pixel with the maximum
      CBV value within the tumors were normalized relative to the contralateral normal
      tissue (rCBV(mean) and rCBV(max), respectively). Karnofsky performance score and
      progression-free survival (PFS) were recorded. Receiver operating characteristic
      curves and Kaplan-Meier survival analysis were conducted for CBV and histologic
      grade (WHO grade). RESULTS: Significant correlations were detected only when
      patients with oligodendrogliomas and oligoastrocytomas were excluded. The
      rCBV(mean) and rCBV(max) in the astrocytomas were 3.5 +/- 2.9 and 3.7 +/- 2.7.
      PFS correlated with rCBV parameters (r = -0.54 to -0.56, P < or = .009). WHO
      grade correlated with rCBV values (r = 0.65, P < or = .0002). rCBV(max) > 4.2 was
      found to be a significant cutoff value for recurrence prediction with 77.8%
      sensitivity and 94.4% specificity (P = .0001). rCBV(max) < or = 3.8 was a
      significant predictor for 1-year survival (93.7% sensitivity, 72.7% specificity,
      P = .0002). The relative risk for shorter PFS was 11.1 times higher for rCBV(max)
      > 4.2 (P = .0006) and 6.7 times higher for WHO grade > II (P = .05). The combined
      CBV-WHO grade classification enhanced the predictive value for
      recurrence/progression (P < .0001). CONCLUSIONS: rCBV values in astrocytomas but
      not tumors with oligodendroglial components are predictive for recurrence and 1
      year survival and may be more accurate than histopathologic grading.

PMID- 19179428
TI  - Heat stroke: increased signal intensity in the bilateral cerebellar dentate
      nuclei and splenium on diffusion-weighted MR imaging.

PMID- 19179430
TI  - Chronic endothelium-dependent regulation of arterial blood pressure by atrial
      natriuretic peptide: role of nitric oxide and endothelin-1.
AB  - Atrial natriuretic peptide (ANP), via its guanylyl cyclase (GC)-A receptor, plays
      a key role in the regulation of arterial blood pressure (ABP) and volume.
      Endothelial-restricted deletion of GC-A in mice [endothelial cell (EC) GC-A
      knockout (KO)] resulted in hypervolemic hypertension, demonstrating that the
      endothelium participates in the hypotensive and hypovolemic actions of ANP.
      Published studies showed that ANP modulates the release of the vasoactive factors
      nitric oxide (NO) and endothelin-1 (ET-1) from cultured endothelia. Based on
      these observations, we examined the role of these endothelial factors in ANP
      dependent vasodilatation (studied in isolated arteries) and chronic regulation of
      ABP (measured in awake mice by tail-cuff plethysmography). ANP induced
      concentration-dependent vasorelaxations of aortic, carotid, and pulmonary
      arteries. These responses were not different between control and EC GC-A KO mice,
      and were significantly enhanced after inhibition of NO synthase [by N(G)-nitro-L
      arginine-methyl ester]. Intravenous administration of N(G)-nitro-L-arginine
      methyl ester to conscious mice significantly increased ABP. The extent of these
      hypertensive reactions was similar in EC GC-A KO mice and control littermates
      (increases in systolic blood pressure by approximately 25 mm Hg). Conversely,
      antagonism of ET-1/endothelin-A receptors with BQ-123 reduced ABP significantly
      and comparably in both genotypes (by approximately 11 mm Hg). Finally, the
      vascular and tissue expression levels of components of the NO system and of
      immunoreactive ET-1 were not different in control and EC GC-A KO mice. We
      conclude that the endothelium, but not modulation of endothelial NO or ET-1,
      participates in the chronic regulation of ABP by ANP.

PMID- 19179429
TI  - Human uterine smooth muscle and leiomyoma cells differ in their rapid 17beta
      estradiol signaling: implications for proliferation.
AB  - Uterine leiomyomas, benign uterine smooth muscle tumors that affect 30% of
      reproductive-aged women, are a significant health concern. The initiation event
      for these tumors is unclear, but 17beta-estradiol (E2) is an established promoter
      of leiomyoma growth. E2 not only alters transcription of E2-regulated genes but
      also can rapidly activate signaling pathways. The aim of our study is to
      investigate the role of rapid E2-activated cytoplasmic signaling events in the
      promotion of leiomyomas. Western blot analysis revealed that E2 rapidly increases
      levels of phosphorylated protein kinase C alpha (PKC alpha) in both immortalized
      uterine smooth muscle (UtSM) and leiomyoma (UtLM) cell lines, but increases
      levels of phosphorylated ERK1/2 only in UtLM cells. Our studies demonstrate a
      paradoxical effect of molecular and pharmacological inhibition of PKC alpha on
      ERK1/2 activation and cellular proliferation in UtLM and UtSM cells. PKC alpha
      inhibition decreases levels of phosphorylated ERK1/2 and proliferation in UtLM
      cells but raises these levels in UtSM cells. cAMP-PKA signaling is rapidly
      activated only in UtSM cells with E2 and inhibits ERK1/2 activation and
      proliferation. We therefore propose a model whereby E2's rapid activation of PKC
      alpha and cAMP-PKA signaling plays a central role in the maintenance of a low
      proliferative index in normal uterine smooth muscle via its inhibition of the
      MAPK cascade and these pathways are altered in leiomyomas to promote MAPK
      activation and proliferation. These studies demonstrate that rapid E2-signaling
      pathways contribute to the promotion of leiomyomas.

PMID- 19179431
TI  - Brain-derived neurotrophic factor/tropomyosin-related kinase receptor type B
      signaling is a downstream effector of the brainstem melanocortin system in food
      intake control.
AB  - It has been shown that the neurotropin brain-derived neurotrophic factor (BDNF)
      and its high-affinity receptor, tropomyosin-related kinase receptor type B
      (TrkB), contribute to the central control of food intake. BDNF has previously
      been implicated as a probable downstream effector of melanocortinergic signaling
      within the ventromedial hypothalamus, and we have shown its implication as an
      anorexigenic factor within the brainstem autonomic integrator of food intake
      control, namely the dorsal vagal complex (DVC). In the brainstem, the
      melanocortinergic signaling pathway is known to integrate phasic responses to
      satiety signals, such as cholecystokinin. In this study, we explored the
      interactions between melanocortin and BDNF/TrkB signaling within the DVC. First,
      we tested the effect of a local pharmacological activation or inhibition of
      melanocortin receptors type 3/4 (MC3/4R) on BDNF protein content in the DVC of
      adult rats. We showed that fourth intracerebroventricular delivery of MC3/4R
      agonist and antagonist increased and decreased the BDNF protein content within
      the DVC, respectively. Second, we showed that the orexigenic effect of a
      selective MC4R antagonist delivered fourth-icv can be blocked by a
      coadministration of BDNF. We also tested the causal role of BDNF/TrkB signaling
      in the anorexigenic effect of melanocortinergic signaling by using a recently
      developed analog-sensitive kinase allele murine model (TrkB(F616A) mice) and
      showed that the pharmacological blockade of TrkB abolished the anorexigenic
      effect of a selective MC4R agonist and of cholecystokinin. Our results provide
      strong evidence for a role of BDNF as a downstream effector of melanocortinergic
      signaling pathway within the DVC.

PMID- 19179432
TI  - Tanycyte pyroglutamyl peptidase II contributes to regulation of the hypothalamic
      pituitary-thyroid axis through glial-axonal associations in the median eminence.
AB  - Pyroglutamyl peptidase II (PPII), a highly specific membrane-bound
      metallopeptidase that inactivates TRH in the extracellular space, is tightly
      regulated by thyroid hormone in cells of the anterior pituitary. Whether PPII has
      any role in the region where axons containing hypophysiotropic TRH terminate, the
      median eminence, is unknown. For this purpose, we analyzed the cellular
      localization and regulation of PPII mRNA in the mediobasal hypothalamus in adult,
      male rats. PPII mRNA was localized in cells lining the floor and infralateral
      walls of the third ventricle and coexpressed with vimentin, establishing these
      cells as tanycytes. PPII mRNA extended in a linear fashion from the tanycyte cell
      bodies in the base of the third ventricle to its cytoplasmic and end-feet
      processes in the external zone of the median eminence in close apposition to pro
      TRH-containing axon terminals. Compared with vehicle-treated, euthyroid controls,
      animals made thyrotoxic by the i.p. administration of 10 microg L-T(4) daily for
      1-3 d, showed dramatically increased accumulation of silver grains in the
      mediobasal hypothalamus and an approximately 80% increase in enzymatic activity.
      PPII inhibition in mediobasal hypothalamic explants increased TRH secretion,
      whereas i.p. injection of a specific PPII inhibitor increased cold stress- and
      TRH-induced TSH levels in plasma. We propose that an increase in circulating
      thyroid hormone up-regulates PPII activity in tanycytes and enhances degradation
      of extracellular TRH in the median eminence through glial-axonal associations,
      contributing to the feedback regulation of thyroid hormone on anterior pituitary
      TSH secretion.

PMID- 19179433
TI  - Peroxisome-proliferator receptor gamma represses hepatic sex hormone-binding
      globulin expression.
AB  - Plasma SHBG production by the liver is influenced by its metabolic state, and
      hepatocyte nuclear factor-4alpha regulates SHBG expression in response to changes
      in lipogenesis. Peroxisome-proliferator receptors (PPARs) also regulate glucose
      homeostasis and fatty acid metabolism. The human SHBG promoter contains a PPAR
      response element (PPAR-RE), and plasma SHBG levels increase in polycystic ovarian
      syndrome patients treated with the PPARgamma agonist, rosiglitazone. In addition,
      plasma SHBG levels are associated with a genetic polymorphism in the PPARgamma-2
      coding sequence that alters its transcriptional activity. Therefore, we set out
      to determine whether PPARgamma influences hepatic production of SHBG by using
      human HepG2 hepatoblastoma cells as an in vitro model. Surprisingly, treatment of
      HepG2 cells with rosiglitazone reduced SHBG production and SHBG promoter activity
      (as assessed in a luciferase reporter gene assay) by 20-25%, whereas the
      PPARgamma antagonist, GW9662, increased both by 2- to 3-fold. The effects of
      PPARgamma agonists and antagonists on SHBG promoter activity were substantially
      diminished when the PPAR-RE in the SHBG promoter was mutated. A PPARgamma small
      interfering RNA also increased SHBG production by HepG2 cells as well as SHBG
      promoter activity, and the latter was accentuated by cotreatment with GW9662.
      Importantly, overexpression of a PPARgamma-2 Pro12 variant in HepG2 cells was
      more effective at reducing SHBG promoter activity, when compared with PPARgamma-2
      Ala12, consistent with its superior PPAR-RE binding activity. We conclude that
      PPARgamma represses human SHBG expression in liver cells, and that differences in
      PPARgamma levels and activity contribute directly to variations in plasma SHBG
      levels.

PMID- 19179434
TI  - Minireview: Thyrotropin-releasing hormone and the thyroid hormone feedback
      mechanism.
AB  - Thyroid hormone (TH) plays a critical role in development, growth, and cellular
      metabolism. TH production is controlled by a complex mechanism of positive and
      negative regulation. Hypothalamic TSH-releasing hormone (TRH) stimulates TSH
      secretion from the anterior pituitary. TSH then initiates TH synthesis and
      release from the thyroid gland. The synthesis of TRH and TSH subunit genes is
      inhibited at the transcriptional level by TH, which also inhibits
      posttranslational modification and release of TSH. Although opposing TRH and TH
      inputs regulate the hypothalamic-pituitary-thyroid axis, TH negative feedback at
      the pituitary was thought to be the primary regulator of serum TSH levels.
      However, study of transgenic animals showed an unexpected, dominant role for TRH
      in regulating the hypothalamic-pituitary-thyroid axis and an unanticipated
      involvement of the thyroid hormone receptor ligand-dependent activation function
      (AF-2) domain in TH negative regulation. These results are summarized in the
      review.

PMID- 19179435
TI  - Role of estradiol in cortisol-induced reduction of luteinizing hormone pulse
      frequency.
AB  - Precise control of pulsatile GnRH and LH release is imperative to ovarian
      cyclicity but is vulnerable to environmental perturbations, like stress. In
      sheep, a sustained (29 h) increase in plasma cortisol to a level observed during
      stress profoundly reduces GnRH pulse frequency in ovariectomized ewes treated
      with ovarian steroids, whereas shorter infusion (6 h) is ineffective in the
      absence of ovarian hormones. This study first determined whether the ovarian
      steroid milieu or duration of exposure is the relevant factor in determining
      whether cortisol reduces LH pulse frequency. Prolonged (29 h) cortisol infusion
      did not lower LH pulse frequency in ovariectomized ewes deprived of ovarian
      hormones, but it did so in ovariectomized ewes treated with estradiol and
      progesterone to create an artificial estrous cycle, implicating ovarian steroids
      as the critical factor. Importantly, this effect of cortisol was more pronounced
      after the simulated preovulatory estradiol rise of the artificial follicular
      phase. The second experiment examined which component of the ovarian steroid
      milieu enables cortisol to reduce LH pulse frequency in the artificial follicular
      phase: prior exposure to progesterone in the luteal phase, low early follicular
      phase estradiol levels, or the preovulatory estradiol rise. Basal estradiol
      enabled cortisol to decrease LH pulse frequency, but the response was potentiated
      by the estradiol rise. These findings lead to the conclusion that ovarian
      steroids, particularly estradiol, enable cortisol to inhibit LH pulse frequency.
      Moreover, the results provide new insight into the means by which gonadal
      steroids, and possibly reproductive status, modulate neuroendocrine responses to
      stress.

PMID- 19179436
TI  - Elevated glucocorticoid levels are responsible for induction of tyrosine
      hydroxylase mRNA expression, phosphorylation, and enzyme activity in the nucleus
      of the solitary tract during morphine withdrawal.
AB  - Chronic opiate exposure induces neurochemical adaptations in the noradrenergic
      system. Enhanced responsiveness of the hypothalamo-pituitary-adrenal axis after
      morphine withdrawal has been associated with hyperactivity of ascending
      noradrenergic input from the nucleus of the solitary tract (NTS-A(2)) cell group
      to the hypothalamic paraventricular nucleus (PVN). This study addressed the role
      of morphine withdrawal-induced corticosterone (CORT) release in regulation of
      tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis
      in adrenalectomized (ADX) rats supplemented with low CORT pellet (ADX plus CORT).
      Present results show that in sham-ADX rats, noradrenergic neurons in the NTS-A(2)
      became activated during morphine withdrawal, as indicated by increased TH mRNA
      expression. However, this induction of TH expression is not detected in ADX plus
      CORT rats that are unable to mount CORT secretory response to morphine
      withdrawal. Total TH protein levels were elevated in the NTS-A(2) from sham
      operated rats during morphine dependence and withdrawal, whereas we did not find
      any alteration in ADX plus CORT animals. Furthermore, high levels of TH
      phosphorylated (activated) at Ser31 (but not at Ser40) were found in the A(2)
      area from sham-morphine withdrawn rats. Consistent with these effects, we
      observed an increase in the enzyme activity of TH in the PVN. However, induction
      of morphine withdrawal to ADX plus CORT animals did not alter the phosphorylation
      (activation) of TH in NTS-A(2) and decreased TH activity in the PVN. These
      results suggest the existence of a positive reverberating circle in which
      elevated glucocorticoids during morphine abstinence play a permissive role in
      morphine withdrawal-induced activation of noradrenergic pathway innervating the
      PVN.

PMID- 19179437
TI  - Leptin indirectly regulates gonadotropin-releasing hormone neuronal function.
AB  - The adipose-derived hormone leptin communicates information about metabolic
      status to the hypothalamic GnRH neuronal system. It is unclear whether leptin can
      act directly on GnRH neurons. To examine this, we used three approaches. First,
      the presence of leptin-induced signal transducer and activator of transcription-3
      activation was examined in GnRH neurons in male and female rats.
      Intracerebroventricular treatment with 4 mug leptin-induced robust signal
      transducer and activator of transcription-3 expression within the anteroventral
      periventricular nucleus but not in GnRH neurons. Second, fertility was assessed
      in male and female CRE-loxP transgenic mice with conditional leptin receptor
      (Lepr) deletion from either all forebrain neurons or GnRH neurons only. Forebrain
      neuron LEPR deletion prevented the onset of puberty resulting in infertility in
      males and females and blocked estradiol-induced LH surge. However, mice with GnRH
      neuron-selective Lepr deletion exhibited normal fertility apart from a slight
      puberty delay in males. Lastly, the highly sensitive technique of single-cell
      nested PCR was used to test for Lepr transcript presence in individual GnRH
      neurons, identified in situ using GnRH-green fluorescent protein transgenics.
      Whereas 75% of positive control (proopiomelanocortin) neurons contained Lepr
      mRNA, no (none of 18) GnRH neurons were Lepr mRNA positive. Collectively, these
      results show that leptin does not act directly on GnRH neurons in rats and mice.
      Leptin appears to regulate GnRH function via forebrain neurons that are afferent
      to GnRH because forebrain neuronal LEPR deletion caused infertility. The location
      and phenotype of these leptin-responsive neurons remains to be elucidated.

PMID- 19179438
TI  - Retinoic acid reduces glucocorticoid sensitivity in C2C12 myotubes by decreasing
      11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor
      activities.
AB  - Vitamin A is a nutrient with remarkable effects on adipose tissue and skeletal
      muscles, and plays a role in controlling energy balance. Retinoic acid (RA), the
      carboxylic form of vitamin A, has been associated with improved glucose tolerance
      and insulin sensitivity. In contrast, elevated glucocorticoids have been
      implicated in the development of insulin resistance and impaired glucose
      tolerance. Here, we investigated whether RA might counteract glucocorticoid
      effects in skeletal muscle cells by lowering 11beta-hydroxysteroid dehydrogenase
      type 1 (11beta-HSD1)-dependent local glucocorticoid activation and/or activation
      of glucocorticoid receptor (GR). We found a dose-dependent down-regulation of
      11beta-HSD1 mRNA expression and activity upon incubation of fully differentiated
      mouse C2C12 myotubes with RA. In addition, RA inhibited GR transactivation by an
      11beta-HSD1-independent mechanism. The presence of RA during myogenesis did not
      prevent myotube formation but resulted in relatively glucocorticoid-resistant
      myotubes, exhibiting very low 11beta-HSD1 expression and GR activity. The use of
      selective retinoic acid receptor (RAR) and retinoid X receptor ligands provided
      evidence that these effects were mediated through RARgamma. Importantly, short
      hairpin RNA against RARgamma abolished the effect of RA on 11beta-HSD1 and GR. In
      conclusion, we provide evidence for an important role of RA in the control of
      glucocorticoid activity during myogenesis and in myotubes. Disturbances of the
      nutrient and hormonal regulation of glucocorticoid action in skeletal muscles
      might be relevant for metabolic diseases.

PMID- 19179440
TI  - Molecular determinants of oocyte competence: potential functional role for
      maternal (oocyte-derived) follistatin in promoting bovine early embryogenesis.
AB  - Previous studies established a positive relationship between oocyte competence
      and follistatin mRNA abundance. Herein, we used the bovine model to test the
      hypothesis that follistatin plays a functional role in regulation of early
      embryogenesis. Treatment of early embryos with follistatin during in vitro
      culture (before embryonic genome activation) resulted in a dose-dependent
      decrease in time to first cleavage, increased numbers of blastocysts, and
      increased blastocyst total and trophectoderm cell numbers. To determine the
      requirement of endogenous follistatin for early embryogenesis, follistatin
      ablation/replacement studies were performed. Microinjection of follistatin small
      interfering RNA into zygotes reduced follistatin mRNA and protein and was
      accompanied by a reduction in number of embryos developing to eight- to 16-cell
      and blastocyst stages and reduced blastocyst total and trophectoderm cell
      numbers. Effects of follistatin ablation were rescued by culture of follistatin
      small interfering RNA-injected embryos in the presence of exogenous follistatin.
      To investigate whether follistatin regulation of early embryogenesis is
      potentially mediated via inhibition of endogenous activin activity, the effects
      of treatment of embryos with exogenous activin, SB-431542 (inhibitor of activin,
      TGF-beta, and nodal type I receptor signaling) and follistatin plus SB-431542
      were investigated. Activin treatment mimicked positive effects of follistatin on
      time to first cleavage and blastocyst development, whereas negative effects of SB
      431542 treatment were observed. Stimulatory effects of follistatin on
      embryogenesis were not blocked by SB-431542 treatment. Results support a
      functional role for oocyte-derived follistatin in bovine early embryogenesis and
      suggest that observed effects of follistatin are likely not mediated by classical
      inhibition of activin activity.

PMID- 19179441
TI  - Minireview: Pathophysiological importance of thyroid hormone transporters.
AB  - Thyroid hormone metabolism and action are largely intracellular events that
      require transport of iodothyronines across the plasma membrane. It has been
      assumed for a long time that this occurs by passive diffusion, but it has become
      increasingly clear that cellular uptake and efflux of thyroid hormone is mediated
      by transporter proteins. Recently, several active and specific thyroid hormone
      transporters have been identified, including monocarboxylate transporter 8
      (MCT8), MCT10, and organic anion transporting polypeptide 1C1 (OATP1C1). The
      latter is expressed predominantly in brain capillaries and transports
      preferentially T(4), whereas MCT8 and MCT10 are expressed in multiple tissues and
      are capable of transporting different iodothyronines. The pathophysiological
      importance of thyroid hormone transporters has been established by the
      demonstration of MCT8 mutations in patients with severe psychomotor retardation
      and elevated serum T(3) levels. MCT8 appears to play an important role in the
      transport of thyroid hormone in the brain, which is essential for the crucial
      action of the hormone during brain development. It is expected that more specific
      thyroid hormone transporters will be discovered in the near future, which will
      lead to a better understanding of the tissue-specific regulation of thyroid
      hormone bioavailability.

PMID- 19179439
TI  - Minireview: Defining the roles of the iodothyronine deiodinases: current concepts
      and challenges.
AB  - As is typical of other hormone systems, the actions of the thyroid hormones (TH)
      differ from tissue to tissue depending upon a number of variables. In addition to
      varying expression levels of TH receptors and transporters, differing patterns of
      TH metabolism provide a critical mechanism whereby TH action can be
      individualized in cells depending on the needs of the organism. The iodothyronine
      deiodinases constitute a family of selenoenzymes that selectively remove iodide
      from thyroxine and its derivatives, thus activating or inactivating these
      hormones. Three deiodinases have been identified, and much has been learned
      regarding the differing structures, catalytic activities, and expression patterns
      of these proteins. Because of their differing properties, the deiodinases appear
      to serve varying functions that are important in regulating metabolic processes,
      TH action during development, and feedback control of the thyroid axis. This
      review will briefly assess these functional roles and others proposed for the
      deiodinases and examine some of the current challenges in expanding our knowledge
      of these important components of the thyroid homeostatic system.

PMID- 19179442
TI  - Reduced energy expenditure and increased inflammation are early events in the
      development of ovariectomy-induced obesity.
AB  - Menopause, an age-related loss of ovarian hormone production, promotes increased
      adiposity and insulin resistance. However, the diet-independent mechanism by
      which loss of ovarian function promotes increased adipose tissue mass and
      associated metabolic pathologies remains unclear. To address this question, we
      monitored food intake and weight gain of ovariectomized (OVX) mice and sham OVX
      (SHM) mice for 12 wk. Although food intake was similar, OVX mice gained 25% more
      weight than SHM mice. Moreover, the OVX mice accumulated 4.7- and 4.4-fold more
      perigonadal and inguinal adipose tissue by weight, respectively, with 4.4-fold
      (perigonadal, P < 0.001) and 5.3-fold (inguinal, P < 0.01) larger adipocytes and
      no change in adipocyte cell number. OVX-induced adiposity was coincident with an
      18% decrease in metabolic rate during the dark phase (P = 0.001) as well as an
      11% decrease during the light phase (P = 0.03). In addition, ambulatory activity
      levels of OVX mice were decreased only during the dark phase (40%, P = 0.008).
      OVX mice displayed evidence of immune infiltration and inflammation in adipose
      tissue, because perigonadal and inguinal adipose depots from OVX mice had
      increased expression of TNFalpha, iNOS, CD11c, and other hallmarks of adipose
      tissue inflammation. In contrast, expression of the T cell marker CD3 (3.5-fold,
      P = 0.03) and Th1 cytokine interferon-gamma (IFNgamma) (2.6-fold, P = 0.02) were
      elevated in perigonadal but not sc fat. Finally, histology revealed OVX-specific
      liver hepatic steatosis, coincident with increased PPARgamma gene expression and
      downstream lipogenic gene expression. In summary, OVX in mice decreases energy
      expenditure, without altering energy intake, resulting in adipocyte hypertrophy,
      adipose tissue inflammation, and hepatic steatosis.

PMID- 19179443
TI  - Stathmin, a microtubule regulatory protein, is associated with hypoxia-inducible
      factor-1alpha levels in human endometrial and endothelial cells.
AB  - Local hypoxia that occurs during menstruation triggers angiogenesis that is
      crucial for cyclical remodeling of the endometrium during the menstrual cycle.
      Hypoxia is thought to be important for the expression of vascular endothelial
      growth factor (VEGF) via its transcriptional factor, hypoxia inducible factor
      (HIF)-1alpha, in the endometrium. The activation of the phosphatidylinositol-3
      kinase (PI3K)/Akt signaling pathway may modulate HIF-1alpha protein levels.
      Stathmin, a microtubule regulatory protein, was expressed in the stroma,
      glandular epithelium, and vascular endothelium in human endometrium. In this
      study, we examined a possible role of stathmin in hypoxia-induced HIF-1alpha and
      VEGF expression in primary isolated and immortalized human endometrial stromal
      cells, glandular epithelial cells, and human umbilical venous endothelial cells
      (HUVEC). Knocking down stathmin expression using small interfering RNA caused
      microtubule stabilization and inhibited hypoxia-induced VEGF mRNA expression via
      the reduction of HIF-1alpha protein levels in endometrial cells and HUVEC.
      Treatment of the cells with a PI3K inhibitor, wortmannin, inhibited the
      expression of VEGF mRNA and the accumulation of HIF-1alpha protein. Silencing of
      stathmin expression repressed the activation (phosphorylation) of Akt in
      endometrial cells and HUVEC. These results suggest that endometrial stathmin is
      linked to HIF-1alpha protein accumulation and VEGF expression through the
      PI3K/Akt signaling pathway and may be involved in regeneration of the endometrium
      during the menstrual cycle in human uterine cells.

PMID- 19179444
TI  - Postreceptoral adipocyte insulin resistance induced by nelfinavir is caused by
      insensitivity of PKB/Akt to phosphatidylinositol-3,4,5-trisphosphate.
AB  - Adipocyte insulin resistance can be caused by proximal insulin signaling defects
      but also from postreceptor mechanisms, which in large are poorly characterized.
      Adipocytes exposed for 18 h to the HIV protease inhibitor nelfinavir manifest
      insulin resistance characterized by normal insulin-stimulated tyrosine
      phosphorylation of the insulin receptor and insulin receptor substrate proteins,
      preserved in vitro phosphatidylinositol 3-kinase (PI 3-kinase) assay activity but
      impaired activation of PKB/Akt and stimulation of glucose uptake. Here we aimed
      to assess whether impaired PKB/Akt activation is indeed rate limiting for insulin
      signaling propagation in response to nelfinavir and the mechanism for defective
      PKB/Akt activation. Nelfinavir treatment of 3T3-L1 adipocytes impaired the
      insulin-stimulated translocation and membrane fusion of myc-glucose transporter
      (GLUT)-4-green fluorescent protein (GFP) reporter. Phosphorylation of PKB/Akt
      substrates including glycogen synthase kinase-3 and AS160 decreased in response
      to nelfinavir, and this remained true, even in cells with forced generation of
      phosphatidylinositol-3,4,5-trisphohphate (PIP(3)) by a membrane-targeted active
      PI 3-kinase, confirming that impaired PKB/Akt activation was rate limiting for
      insulin signal propagation. Cells expressing a GFP-tagged pleckstrin homology
      domain of general receptors for phosphoinositides 1, which binds PIP(3), revealed
      intact PIP(3)-mediated plasma membrane translocation of this reporter in
      nelfinavir-treated cells. However, expression of a membrane-targeted catalytic
      subunit of PI 3-kinase failed to induce myc-GLUT4-GFP translocation in the
      absence of insulin, as it did in control cells. Conversely, a membrane-targeted
      and constitutively active PKB/Akt mutant was normally phosphorylated on S473 and
      T308, confirming intact PKB/Akt kinases activity, and induced myc-GLUT4-GFP
      translocation. Collectively, nelfinavir uncovers a postreceptor mechanism for
      insulin resistance, caused by interference with the sensing of PIP(3) by PKB/Akt,
      leading to impaired GLUT4 translocation and membrane fusion.

PMID- 19179445
TI  - Mechanisms of resistance to structurally diverse antiestrogens differ under
      premenopausal and postmenopausal conditions: evidence from in vitro breast cancer
      cell models.
AB  - This study questioned whether the mechanisms of resistance to antiestrogens
      differ when acquired under premenopausal (Pre-M) vs. postmenopausal (PM)
      conditions and whether structurally diverse antiestrogens induce adaptation of
      differing signaling pathways. To address this issue, we conducted systematic
      studies under Pre-M vs. PM culture conditions with long-term exposure to
      different antiestrogens and examined the resultant "specific biologic signatures"
      of the various resistant cells. Estradiol stimulated growth and inhibited
      apoptosis of "pre-menopausal" antiestrogen-resistant cells but exerted opposite
      effects on their "post-menopausal" counterparts. Under Pre-M conditions,
      tamoxifen (TAM)-resistant cells exhibited a marked translocation of estrogen
      receptor alpha from the nucleus into the cytoplasm, whereas this occurred to a
      lesser extent under PM conditions. MCF-7 cells exposed to PM but not Pre-M
      conditions exhibited up-regulation of basal epidermal growth factor (EGF)
      receptor (EGFR) levels, an effect exaggerated in cells exposed to 4
      hydroxytamoxifen. Differing effects occurred in response to structurally
      divergent antiestrogens. Long-term treatment with both 4-hydroxytamoxifen and
      ICI182,780 increased EGFR levels, but this was not seen in response to TAM.
      Surprisingly, EGF administration slightly increased cell number in TAM-resistant
      cells, whereas only increasing cell weight and decreasing cell number in EGFR
      overexpressing-resistant cells. To assess potential differences among various
      parental cell lines, we induced resistance in cell lines obtained from other
      laboratories and confirmed the results from our own parental cells with minor
      differences. Together, these data demonstrate that culture of breast cancer cells
      under Pre-M and PM conditions and structurally diverse antiestrogens results in
      adaptive responses with differing biological signatures.

PMID- 19179446
TI  - Coingestion of acylglycerols differentially affects glucose-induced insulin
      secretion via glucose-dependent insulinotropic polypeptide in C57BL/6J mice.
AB  - The precise role of fat in postprandial glycemia and insulinemia has not been
      thoroughly researched because postprandial blood glucose and concurrent insulin
      secretion are largely assumed to be proportional to carbohydrate intake. Recent
      studies have suggested that dietary fat differentially regulates the postprandial
      insulin response. To explore this, we examined the effects of coadministered fat
      on glucose-induced glycemia and insulinemia in C57BL/6J mice. The insulin
      response to glucose was augmented by the addition of glycerol trioleate (TO) in a
      dose-dependent manner, which was associated with enhanced glucose transport from
      the circulation to muscle and adipose tissues. To investigate the mechanism
      underlying fat-induced hyperinsulinemia, we examined the release of the incretin
      hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like
      peptide-1. TO increased GIP secretion, whereas glucagon-like peptide-1 secretion
      was unaffected. TO-induced hyperinsulinemia was significantly attenuated by the
      pretreatment of mice with a specific GIP antagonist. Diacylglycerol (DAG)
      promoted lower postprandial GIP and triglyceride responses and, when ingested
      with glucose, a lower insulin response compared with triacylglycerol of a similar
      fatty acid composition. Pluronic L-81, an inhibitor of chylomicron formation,
      reduced not only the triglyceride response but also TO-induced GIP secretion,
      indicating that the lower GIP response after DAG ingestion may be associated with
      retarded chylomicron formation in the small intestine. We conclude that dietary
      fat augments glucose-induced insulinemia via gut-derived GIP and, thereby,
      influences postprandial nutrient metabolism in mice. DAG promotes a lower GIP and
      thereby reduced insulin responses compared with triacylglycerol, which may
      differentially influence postprandial energy homeostasis.

PMID- 19179447
TI  - The role of mPer2 clock gene in glucocorticoid and feeding rhythms.
AB  - The circadian clock synchronizes the activity level of an organism to the light
      dark cycle of the environment. Energy intake, as well as energy metabolism, also
      has a diurnal rhythm. Although the role of the clock genes in the sleep-wake
      cycle is well characterized, their role in the generation of the metabolic
      rhythms is poorly understood. Here, we use mice deficient in the clock protein
      mPer2 to study how the circadian clock regulates two critical metabolic rhythms:
      glucocorticoid and food intake rhythms. Our findings indicate that mPer2-/- mice
      do not have a glucocorticoid rhythm even though the corticosterone response to
      hypoglycemia, ACTH, and restraint stress is intact. In addition, the diurnal
      feeding rhythm is absent in mPer2-/- mice. On high-fat diet, they eat as much
      during the light period as they do during the dark period and develop significant
      obesity. The diurnal rhythm of neuroendocrine peptide alphaMSH, a major effector
      of appetite control, is disrupted in the hypothalamus of mPer2-/- mice even
      though the diurnal rhythm of ACTH, the alphaMSH precursor, is intact. Peripheral
      injection of alphaMSH, which has been shown to enter the brain, restored the
      feeding rhythm and induced weight loss in mPer2-/- mice. These findings emphasize
      the requirement of mPer2 in appetite control during the inactive period and the
      potential role of peripherally administered alphaMSH in restoring night-day
      eating pattern in individuals with circadian eating disorders such as night
      eating syndrome, which is also associated with obesity.

PMID- 19179448
TI  - The unethical focus on access: a study of medical ethics and the waiting-time
      guarantee.
AB  - AIM: All civilized societies favour ethical principles of equity. In healthcare,
      these principles generally focus on needs for medical care. Methods for
      establishing priorities among such needs are instrumental in this process. In
      this study, we analysed whether rules on access to healthcare, waiting-time
      guarantees, conflict with ethical principles of distributive justice. METHODS: We
      interviewed directors, managers and other decision-makers of various healthcare
      providers of hospitals, primary care organizations and purchasing offices. We
      also conducted focus group interviews with professionals from a number of
      distinct medical areas. RESULTS: Our informants and their co-workers were
      reasonably familiar with the ethical platforms for priority-setting established
      by the Swedish parliament, giving the sickest patients complete priority.
      However, to satisfy the waiting-time guarantees, the informants often had to make
      priority decisions contrary to the ethical principles by favouring access before
      needs to keep waiting times within certain limits. The common opinion was that
      the waiting-time guarantee leads to crowding-out effects, overruling the ethical
      principles based on needs. CONCLUSIONS: For more than a decade, the
      interpretation in Sweden of the equitable principle based on medical needs has
      been distorted through political decisions, leading to healthcare providers
      giving priority to access rather than needs for care.

PMID- 19179449
TI  - Intentions to retire, life dissatisfaction and the subsequent risk of disability
      retirement.
AB  - BACKGROUND AND AIMS: To examine the predictive value of intentions to retire
      early on the process of disability retirement and the contribution of life
      dissatisfaction to the association between intentions to retire early and
      disability retirement. METHODS: A cohort of 6484 employees over 40 years and
      working for the City of Helsinki was followed from 2000 to 2004. At baseline, the
      participants had responded to a questionnaire. Information on disability
      retirement was obtained from the Local Government Pensions Institution and the
      State Treasury. We calculated age and gender adjusted incidence rates and
      estimated Cox regression models. RESULTS: During the follow-up 232 (3.6%)
      participants were granted a disability pension. Clear predictive value of
      disability retirement was found for strong intentions to retire early (age and
      gender adjusted hazard ratio HR 6.55, 95% CI 4.64-9.26) and for life
      dissatisfaction (dissatisfaction with subjective well-being, HR 5.31, 4.11-6.87).
      After adjusting for life dissatisfaction, the HR for those with strong intentions
      to retire early attenuated to 3.86 (2.66-5.62). After simultaneous adjustments
      for various risk factors the associations of intentions to retire early and
      dissatisfaction with subjective well-being with disability retirement attenuated,
      but remained statistically significant. CONCLUSIONS: The impact of intentions and
      subjective experience of well-being as measured by life dissatisfaction to the
      process of disability retirement should be recognized. Intentions to retire and
      life dissatisfaction should be considered as suitable measures when identifying
      people with elevated risk of disability retirement.

PMID- 19179450
TI  - Review article: communicable diseases surveillance lessons learned from developed
      and developing countries: literature review.
AB  - BACKGROUND: Surveillance of infectious diseases is recognized as the cornerstone
      of public health decision-making and practice. The aim of the evaluation of
      communicable diseases surveillance systems (CDSS) is ensuring that communicable
      diseases are monitored efficiently and effectively. The aim of this paper is to
      reflect on the experiences of both developed and developing countries in the
      evaluation of CDSS in order to learn lessons from these experiences to improve
      systems everywhere. METHODS: A literature review of studies published in English
      in PubMed and databases of the World Health Organization (WHO), and Center of
      Diseases Control (CDC) from 1981 to 2007 was undertaken assessing CDSS. The
      studies were divided into those from developed and developing countries. RESULTS:
      A total of 32 studies were included, 20 from developed and twelve from developing
      countries. Both developed and developing countries faced difficulties in CDSS.
      Studies from the developed countries have been analysed based on the quality of
      the system alone. In developing countries, most of the studies have been on the
      integrated diseases surveillance (IDSR) and have been performed shortly after the
      adoption of the IDSR. Thus it might be too early to make a fair evaluation. Some
      of the systems over-centralized, while some lacked private health sector
      involvement in the system. Further, some of the systems were affected by
      conflicts and civil wars which are common problems in developing countries.
      CONCLUSIONS: None of the countries had ideal CDSS. The strategy of integrated
      diseases surveillance seems to be functioning well especially in Africa.

PMID- 19179451
TI  - Mortality among disability pensioners in Norway and Sweden 1990--96: comparative
      prospective cohort study.
AB  - AIM: The aim of the study was to assess excess mortality related to disability
      pension (DP) status and DP diagnoses in Norway and Sweden during 1990-96.
      METHODS: Representative samples of the population aged 30-59 years, without DP at
      baseline 1 January 1990, 71,293 women and 76,928 men from Norway, and 68,181
      women and 71,950 men from Sweden, were followed up during 1990-96. Granting of
      DP, DP diagnosis, age and gender were explanatory variables in Cox proportional
      hazards analysis with death from all causes as the outcome variable. RESULTS:
      Among women, 10.4% in Sweden and 7.1% in Norway obtained DP, as compared to 7.5%
      and 5.6% of the men. In Sweden, 66% of female and 49% of male DP recipients had
      musculoskeletal diagnoses, as compared to 40% and 27% in Norway. In Sweden, 3.0%
      of the women and 6.1% of the men with DP died, as compared to 4.6% and 8.5% in
      Norway. Hazard ratios (HRs) for women with DP vs. the non-DP group were 3.2 (95%
      confidence interval (CI)=2.7-3.8) in Sweden, and 4.9 (95% CI=4.1-5.7) in Norway.
      Among men with DP, there was no difference in mortality rate between the
      countries. HRs for men with musculoskeletal diagnoses vs. the non-DP group were
      1.5 (95% CI= 1.1-2.0) in Norway and 1.4 (95% CI= 1.1-1.8) in Sweden. In both
      countries, the mortality rate among female disability pensioners with
      musculoskeletal diagnoses was not increased. CONCLUSIONS: The study confirmed an
      increased mortality rate among disability pensioners, except for women with
      musculoskeletal diagnoses. The mortality pattern related to DP diagnoses was
      similar in the two countries. A high frequency of musculoskeletal DP diagnoses
      among women with DP in Sweden explained a lower mortality rate as compared to
      Norway.

PMID- 19179452
TI  - Inductive and suppressive networks regulate TLR9-dependent gene expression in
      vivo.
AB  - Bacterial DNA expressing unmethylated CpG motifs binds to TLR9, thereby
      stimulating a broadly protective, innate immune response. Although CpG-mediated
      signal transduction has been studied, the scope of TLR9-dependent gene expression
      is incompletely understood. To resolve these issues, mice were treated with
      immunostimulatory CpG oligonucleotides (ODN) and splenic mRNA levels monitored
      from 30 min through 3 days by microarray. Through the unique application of
      bioinformatic analysis to these experimental data, this study is the first to
      describe the complex regulatory networks responsible for TLR9-mediated gene
      expression. Current results are the first to establish that CpG-induced
      stimulation of the innate immune system proceeds in multiple waves over time, and
      gene up-regulation is mediated by a small number of temporally activated "major
      inducers" and "minor inducers". An additional study of TNF knockout mice supports
      the conclusion that the regulatory networks identified by our bioinformatic
      analysis accurately identified CpG ODN-driven gene-gene interactions in vivo.
      Equally important, this work identifies the counter-regulatory mechanisms
      embedded within the signaling cascade that suppresses the proinflammatory
      response triggered in vivo by CpG DNA stimulation. Identifying these network
      interactions provides novel and global insights into the regulation of TLR9
      mediated gene activation, improves our understanding of TLR-mediated host
      defense, and facilitates the development of interventions designed to optimize
      the nature and duration of the ensuing response.

PMID- 19179454
TI  - Calcium-sensing receptor mutations and denaturing high performance liquid
      chromatography.
AB  - The calcium-sensing receptor (CASR), a plasma membrane G-protein-coupled
      receptor, is expressed in parathyroid gland and kidney, and controls systemic
      calcium homeostasis. Inactivating CASR mutations are associated with familial
      hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism, and
      activating mutations cause autosomal dominant hypocalcemia (ADH). CASR mutation
      identification plays an important role in the clinical management of mineral
      metabolism disorders. We describe here a high-throughput method using screening
      with denaturing high performance liquid chromatography (DHPLC) to initially
      interrogate 12 amplicons covering translated exons and exon/intron boundaries,
      followed by sequencing of any amplicon with a modified melting curve relative to
      wild type, and direct sequencing of a 13th amplicon encoding the COOH-terminal
      tail to distinguish causative mutations from three common missense single
      nucleotide polymorphisms. A blinded analysis of 32 positive controls representing
      mutations throughout the CASR sequence, as well as 22 negative controls, yielded
      a concordance rate of 100%. We report eight novel and five recurrent FHH
      mutations, along with six novel and two recurrent ADH mutations. Thus, DHPLC
      provides a rapid and effective means to screen for CASR mutations.

PMID- 19179453
TI  - MIF homologues from a filarial nematode parasite synergize with IL-4 to induce
      alternative activation of host macrophages.
AB  - Macrophage migration inhibitory factor (MIF) is a highly conserved cytokine
      considered to exert wide-ranging, proinflammatory effects on the immune system.
      Recently, members of this gene family have been discovered in a number of
      invertebrate species, including parasitic helminths. However, chronic helminth
      infections are typically associated with a Th2-dominated, counter-inflammatory
      phenotype, in which alternatively activated macrophages (AAMs) are prominent. To
      resolve this apparent paradox, we have analyzed the activity of two helminth MIF
      homologues from the filarial nematode Brugia malayi, in comparison with the
      canonical MIF from the mouse. We report that murine MIF (mMIF) and Brugia MIF
      proteins induce broadly similar effects on bone marrow-derived mouse macrophages,
      eliciting a measured release of proinflammatory cytokines. In parallel, MIF was
      found to induce up-regulation of IL-4R on macrophages, which when treated in
      vitro with MIF in combination with IL-4, expressed markers of alternative
      activation [arginase, resistin-like molecule alpha (RELM-alpha) or found in
      inflammatory zone 1, Ym-1, murine macrophage mannose receptor] and differentiated
      into functional AAMs with in vitro-suppressive ability. Consistent with this
      finding, repeated in vivo administration of Brugia MIF induced expression of
      alternative macrophage activation markers. As mMIF did not induce RELM-alpha or
      Ym-1 in vivo, alternative activation may require components of the adaptive
      immune response to Brugia MIF, such as the production of IL-4. Hence, MIF may
      accentuate macrophage activation according to the polarity of the environment,
      thus promoting AAM differentiation in the presence of IL-4-inducing parasitic
      helminths.

PMID- 19179455
TI  - Quantitative fluorescence in situ hybridization and its ability to predict
      bladder cancer recurrence and progression to muscle-invasive bladder cancer.
AB  - Fluorescence in situ hybridization (FISH) testing is used to detect bladder
      cancer in urine specimens. The purpose of this study was to determine whether
      there are associations between the percentage of chromosomally abnormal cells by
      FISH and time to bladder cancer recurrence and progression to metastasis.
      Clinical records were searched to identify patients with urine FISH results,
      history of non-invasive bladder cancer, and at least one follow-up pathological
      diagnosis. Covariates analyzed included age, gender, smoking status, treatment
      after FISH, cystoscopy result, and prior stage of bladder cancer. The percentage
      of abnormal cells (hazard ratio [HR] 1.03, 95% CI 1.02-1.03; P < 0.001), age (HR
      1.02, 95% CI 1.00-1.03; P = 0.033), male gender (HR 0.60, 95% CI 0.41-0.87; P <
      0.001), treatment (HR 0.37, 95% CI 0.25-0.55; P < 0.001), and history of TIS/T1
      stage tumors (HR 1.66, 95% CI 1.23-2.24; P = 0.001) were significantly associated
      with time to cancer recurrence. Time to invasive cancer was significantly
      associated with the percentage of abnormal cells (HR 1.02, 95% CI 1.01, 1.03; P <
      0.001), history of TIS/T1 tumor (HR 3.73, 95% CI 1.88, 7.38; P = 0.001), and
      treatment (HR 0.33, 95% CI 0.13, 0.83; P = 0.019), suggesting that the percentage
      of abnormal cells independently predicts cancer recurrence and progression to
      invasive disease in patients with a history of non-invasive bladder cancer.

PMID- 19179456
TI  - High quality assessment of DNA methylation in archival tissues from colorectal
      cancer patients using quantitative high-resolution melting analysis.
AB  - High-resolution melting (HRM) analysis is a novel tool for analysis of promoter
      methylation. The aim of the present study was to establish and validate HRM
      analysis for detection of promoter methylation on archival formalin-fixed
      paraffin-embedded tissues from colorectal cancer patients. We first evaluated HRM
      assays for O(6)-methylguanine-DNA methyltransferase (MGMT) and adenomatous
      polyposis coli (APC) promoter methylation on a methylated DNA dilution matrix and
      DNA extracted from eight fresh or formalin-fixed paraffin-embedded human cancer
      cell lines. Then we used these assays for the analysis of MGMT and APC promoter
      methylation in a subset of archival formalin-fixed paraffin-embedded colorectal
      tumor specimens. All samples with promoter methylation of MGMT or APC and
      randomly selected samples without promoter methylation were analyzed twice. All
      results generated by HRM were validated with MGMT and APC MethyLight assays. APC
      and MGMT promoter methylation data were consistent and reproducible throughout
      the dilutions and all three replicates in the methylated DNA dilution matrix and
      between two experiments in clinical samples. There was high concordance between
      HRM and MethyLight results. HRM for APC promoter methylation revealed consistent
      results between fresh and formalin-fixed paraffin-embedded human cancer cell line
      DNA. The methylation status in archival tumor specimens from patients with
      colorectal cancer can therefore be determined with high quality by HRM. The
      ability to analyze archival tissues greatly facilitates further research and its
      clinical implementation.

PMID- 19179457
TI  - Gestational thyroid function abnormalities in conditions of mild iodine
      deficiency: early screening versus continuous monitoring of maternal thyroid
      status.
AB  - OBJECTIVE: To longitudinally evaluate the timing of maternal thyroid
      underfunction occurrence in mildly iodine-deficient (ID) pregnant women, and
      ultimately assess the benefit of thyroid function testing at early gestation only
      in identifying maternal thyroid underfunction. PARTICIPANTS/METHODS: Serum free
      thyroxine and TSH were measured in 220 consecutive women once in early pregnancy
      (by week 12) and twice per trimester subsequently. Anti-thyroperoxidase and anti
      thyroglobulin were also determined at initial and final observation. RESULTS:
      Thyroid autoantibodies were detectable in 8.2% women. Overall, the prevalence of
      hypothyroidism over the course of gestation was 11.8% (26/220), with a relative
      risk of hypothyroidism in antibody-positive women of 5.0 (chi(2) 20.02,
      P<0.0005). Nonetheless, almost 70% hypothyroid women tested negative for thyroid
      autoantibodies. Fifteen/26 (57.7%) hypothyroid women were identified at
      presentation, and the remaining 11 at either early (6/11) or late (5/11) phases
      of the 2nd trimester. Isolated hypothyroxinemia was observed in 56/220 (25.4%)
      women, mostly from the 2nd trimester onwards. CONCLUSIONS: In mildly ID areas
      thyroid function testing early in gestation seems to be only partly effective in
      identifying thyroid underfunction in pregnant women. Indeed, in our series more
      than 40% hypothyroid women would not have been diagnosed had we limited our
      observation to early thyroid function tests alone. Although thyroid autoimmunity
      carried a 5-fold increased risk of hypothyroidism, iodine deficiency seems to be
      a major determinant in the occurrence of thyroid underfunction. Adequate iodine
      supplementation should be strongly recommended to meet the increased hormone
      demand over gestation.

PMID- 19179458
TI  - Defective insulin signaling in placenta from pregnancies complicated by
      gestational diabetes mellitus.
AB  - OBJECTIVE: Studies in adipose tissue and skeletal muscle suggest that impaired
      insulin action is due to defects in the insulin signaling pathway and may play a
      role in the pathophysiology of insulin resistance associated with gestational
      diabetes mellitus (GDM) and obesity. The present study tested the hypothesis that
      endogenous expression levels in the human term placenta of insulin signaling
      components are altered in placental tissue from GDM women in comparison with
      normal controls and maternal obesity. DESIGN AND METHODS: Placental tissue was
      collected from normal, diet-controlled GDM, and insulin-controlled GDM in both
      non-obese and obese women (n=6-7 per group). Western blotting and quantitative RT
      PCR was performed to determine the level of expression in the insulin signaling
      pathway. RESULTS: There was a significant increase in insulin receptor (IR)
      substrate (IRS)-1 protein expression with a concurrent decrease in IRS-2 protein
      expression in non-obese women with insulin-controlled GDM compared with diet
      controlled GDM and normal controls. Furthermore, a decrease in both protein and
      mRNA expression of phosphatidyl-inositol-3-kinase (PI3-K) p85alpha and glucose
      transporter (GLUT)-4 was observed in non-obese and obese women with insulin
      controlled GDM compared with normal controls. When comparing non-obese to obese
      patients, significant decreases in mRNA expression of IR-beta, PI3K p85alpha and
      GLUT-4 was found in obese patients. CONCLUSION: Our results suggest that post
      receptor defects are present in the insulin signaling pathway in placenta of
      women with pregnancies complicated by diabetes and obesity. In addition,
      expression studies demonstrate post receptor alterations in insulin signaling
      possibly under selective maternal regulation and not fetal regulation.

PMID- 19179460
TI  - Capture of heat-killed Mycobacterium bovis bacillus Calmette-Guerin by intelectin
      1 deposited on cell surfaces.
AB  - Intelectin is an extracellular animal lectin found in chordata. Although human
      and mouse intelectin-1 recognize galactofuranosyl residues included in cell walls
      of various microorganisms, the physiological function of mammalian intelectin had
      been unclear. In this study, we found that human intelectin-1 was a serum protein
      and bound to Mycobacterium bovis bacillus Calmette-Guerin (BCG). Human intelectin
      1-binding to BCG was inhibited by Ca(2+)-depletion, galactofuranosyl
      disaccharide, ribose, or xylose, and was dependent on the trimeric structure of
      human intelectin-1. Although monomeric, mouse intelectin-1 bound to BCG, with its
      C-terminal region contributing to efficient binding. Human intelectin-1
      transfected cells not only secreted intelectin-1 into culture supernatant but
      also expressed intelectin-1 on the cell surface. The cell surface intelectin-1
      was not a glycosylphosphatidylinositol-anchored membrane protein. Intelectin-1
      transfected cells captured BCG more than untransfected cells, and the BCG
      adherence was inhibited by an inhibitory saccharide of intelectin-1. Intelectin-1
      preincubated cells took up BCG more than untreated cells, but the adhesion of
      intelectin-1-bound BCG was the same as that of untreated BCG. Mouse macrophages
      phagocytosed BCG more efficiently in medium containing mouse intelectin-1 than in
      control medium. These results indicate that intelectin is a host defense lectin
      that assists phagocytic clearance of microorganisms.

PMID- 19179461
TI  - Synthesis of LacdiNAc-terminated glycoconjugates by mutant galactosyltransferase-
      a way to new glycodrugs and materials.
AB  - Human placental beta1,4-galactosyltransferase-I (EC 2.4.1.38) transfers the
      galactosyl moiety from UDP-Gal to various GlcNAc or Glc acceptors in vivo. Here,
      we describe the construction of its Y284L mutant as a His(6)propeptide
      catbeta4GalT1 construct, in which the Gal-transferase activity was totally
      abolished in favor of its GalNAc-transferase activity. We used this mutant in the
      synthesis of three mono- and bivalent LacdiNAc glycomimetics with good yields.
      These compounds proved to be powerful ligands of two activation receptors of
      natural killer cells, NKR-P1 and CD69. A synthetic bivalent tethered di-LacdiNAc
      is the best currently known precipitation agent for both of these receptors and
      has promising potential for the development of immunoactive glycodrugs.

PMID- 19179462
TI  - Career factors help predict productivity in scholarship among faculty members in
      physical therapist education programs.
AB  - BACKGROUND: Academic institutions and scholars play a critical role in the
      development of a unique and substantive professional science and disciplinary
      literature. Individual and environmental characteristics influence the scholarly
      work of higher education faculty generally, but little is known about factors
      that influence scholarly productivity of physical therapist faculty members.
      OBJECTIVE: The purpose of this study was to identify the factors that contribute
      to the variability in scholarly productivity among faculty members in physical
      therapist education programs. DESIGN: A cross-sectional study design was used.
      METHODS: A survey of a representative sample of faculty members in accredited
      professional (entry-level) physical therapist education programs in the United
      States was conducted. Descriptive analysis was conducted, and 5 blocked
      hierarchical regression models were constructed to identify factors that help
      explain variability in grantsmanship, peer-reviewed publications, and peer
      reviewed presentations. RESULTS: A usable response rate of 58% was obtained. The
      520 participants displayed variability in scholarly productivity. The regression
      models explained half of the variance in career publishing productivity and 28%
      to 44% of the variance in productivity in presentations and grants. Career
      factors, including discipline of highest degree, appointment status, and faculty
      rewards, contributed most substantially to the explained variance. Several
      phenomena unique to physical therapy were considered in light of these findings.
      The multidisciplinary nature of the faculty, national trends in faculty hiring
      and appointment, and the status of the DPT-trained faculty cohort all may
      influence physical therapy faculty scholarship. LIMITATIONS: Unidentified errors
      in sampling or reporting may limit the results of this study. CONCLUSIONS: Career
      factors generally predict the largest proportion of explained variance in
      scholarly productivity. Large numbers of questions remain regarding the status of
      scholarship and scholars in physical therapy.

PMID- 19179463
TI  - Factors that influence the clinical decision making of physical therapists in
      choosing a balance assessment approach.
AB  - BACKGROUND: Many methods for examining patients with balance deficits are
      supported by the literature. How or why therapists choose specific balance
      assessment methods during examination of patients remains unclear. OBJECTIVES:
      The aims of this study were: (1) to explore decision making during examination of
      patients with balance deficits, (2) to understand the selection and use of
      assessment methods from the clinician's perspective, and (3) to explore why
      specific methods were selected. DESIGN: A qualitative design using a grounded
      theory approach permitted exploration of clinical decision making. METHODS:
      Eleven therapists were purposefully selected (6 from outpatient offices, 5 from
      inpatient rehabilitation settings) to participate in repeated interviews.
      Credibility of the findings was established through low-inference data, member
      check, and triangulation among participants and multiple data sources. RESULTS: A
      highly individualized approach to patient examination based on therapists'
      practical knowledge emerged from the data, with limited influence of the
      literature. Movement observation was the primary assessment and diagnostic tool.
      When selecting assessment approaches for specific patients, the perceived value
      of information gathered mattered more than testing time. A 3-stage model of
      assessment decision making portrayed both the process and reasons influencing
      therapists' choices. CONCLUSIONS: In the context of the complex and busy nature
      of clinical practice, therapists gathered data that they considered meaningful
      during patient examination. The findings provide insight into factors influencing
      assessment decisions and suggest mechanisms to foster translation of research
      into clinical practice.

PMID- 19179464
TI  - Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes
      multiple myeloma: a prospective study.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant
      plasma-cell proliferative disorder associated with a life-long risk of
      progression to multiple myeloma (MM). It is not known whether MM is always
      preceded by a premalignant asymptomatic MGUS stage. Among 77,469 healthy adults
      enrolled in the nationwide population-based prospective Prostate, Lung,
      Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 71 subjects
      who developed MM during the course of the study in whom serially collected (up to
      6) prediagnostic serum samples obtained 2 to 9.8 years prior to MM diagnosis were
      available. Using assays for monoclonal (M)-proteins
      (electrophoresis/immunofixation) and kappa-lambda free light chains (FLCs), we
      determined longitudinally the prevalence of MGUS and characterized patterns of
      monoclonal immunoglobulin abnormalities prior to MM diagnosis. MGUS was present
      in 100.0% (87.2%-100.0%), 98.3% (90.8%-100.0%), 97.9% (88.9%-100.0%), 94.6%
      (81.8%-99.3%), 100.0% (86.3%-100.0%), 93.3% (68.1%-99.8%), and 82.4% (56.6%
      96.2%) at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In
      approximately half the study population, the M-protein concentration and involved
      FLC-ratio levels showed a yearly increase prior to MM diagnosis. In the present
      study, an asymptomatic MGUS stage consistently preceded MM. Novel molecular
      markers are needed to better predict progression to MM in patients with MGUS.

PMID- 19179465
TI  - Complement fraction 3 binding on erythrocytes as additional mechanism of disease
      in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab.
AB  - In paroxysmal nocturnal hemoglobinuria (PNH) hemolytic anemia is due mainly to
      deficiency of the complement regulator CD59 on the surface of red blood cells
      (RBCs). Eculizumab, an antibody that targets complement fraction 5 (C5), has
      proven highly effective in abolishing complement-mediated intravascular hemolysis
      in PNH; however, the hematologic benefit varies considerably among patients. In
      the aim to understand the basis for this variable response, we have investigated
      by flow cytometry the binding of complement fraction 3 (C3) on RBCs from PNH
      patients before and during eculizumab treatment. There was no evidence of C3 on
      RBCs of untreated PNH patients; by contrast, in all patients on eculizumab (n =
      41) a substantial fraction of RBCs had C3 bound on their surface, and this was
      entirely restricted to RBCs with the PNH phenotype (CD59(-)). The proportion of
      C3(+) RBCs correlated significantly with the reticulocyte count and with the
      hematologic response to eculizumab. In 3 patients in whom (51)Cr labeling of RBCs
      was carried out while on eculizumab, we have demonstrated reduced RBC half-life
      in vivo, with excess (51)Cr uptake in spleen and in liver. Binding of C3 by PNH
      RBCs may constitute an additional disease mechanism in PNH, strongly enhanced by
      eculizumab treatment and producing a variable degree of extravascular hemolysis.

PMID- 19179466
TI  - Increased risk of monoclonal gammopathy in first-degree relatives of patients
      with multiple myeloma or monoclonal gammopathy of undetermined significance.
AB  - We examined whether monoclonal gammopathy of undetermined significance (MGUS) is
      increased in first-degree relatives of multiple myeloma (MM) or MGUS patients.
      Probands were recruited from a population-based prevalence study (MGUS) and the
      Mayo Clinic (MM). Serum samples were collected from first-degree relatives older
      than 40 years and subjected to electrophoresis and immunofixation. The prevalence
      of MGUS in relatives was compared with population-based rates. Nine-hundred
      eleven relatives of 232 MM and 97 MGUS probands were studied. By electrophoresis,
      MGUS was detected in 55 (6%) relatives, and immunofixation identified 28
      additional relatives for an age- and sex-adjusted prevalence of 8.1% (95% CI, 6.3
      to 9.8). The prevalence of MGUS in relatives increased with age (1.9%, 6.9%,
      11.6%, 14.6%, 21.0% for ages 40-49, 50-59, 60-69, 70-79, >/= 80 years,
      respectively; P < .001). Using similar MGUS detection methods, there was a higher
      risk of MGUS in relatives (age-adjusted risk ratio [RR], 2.6; 95% CI, 1.9 to 3.4)
      compared with the reference population. The increased risk was seen among
      relatives of MM (RR, 2.0; 95% CI, 1.4 to 2.8) and MGUS probands (RR, 3.3; 95% CI,
      2.1 to 4.8). The increased risk of MGUS in first-degree relatives of MGUS or MM
      patients implies shared environment and/or genetics.

PMID- 19179467
TI  - Myc sensitizes p53-deficient cancer cells to the DNA-damaging effects of the DNA
      methyltransferase inhibitor decitabine.
AB  - Decitabine (also referred to as 5-aza-2'-deoxycytidine) is a drug that has
      recently been approved by the Food and Drug Administration (FDA) for the
      treatment of myelodysplastic syndrome (MDS). The mechanism of action is believed
      to be the blocking of DNA methylation and thereby reactivating silenced genes
      involved in harnessing MDS. When analyzing reactivation of genes involved in
      Burkitt lymphoma (BL), we discovered that decitabine also sensitizes tumor cells
      by inducing DNA damage. This sensitization is grossly augmented by the MYC
      oncogene, which is overexpressed in BL, and occurs in cells lacking a functional
      p53 tumor suppressor pathway. In p53-deficient BL cells and p53(-/-) mouse embryo
      fibroblasts, Myc overrides a transient G2-block exerted by decitabine via
      activation of Chk1. This triggers aneuploidy and cell death that correlates with,
      but can occur in the absence of, Epstein-Barr virus (EBV) reactivation, caspase
      activation, and/or expression of the BH3-only protein Puma. In vivo modeling of
      Myc-induced lymphoma suggests that decitabine constitutes a potential new drug
      against lymphoma that would selectively sensitize tumor cells but spare normal
      tissue.

PMID- 19179468
TI  - Leukemogenic Ptpn11 causes fatal myeloproliferative disorder via cell-autonomous
      effects on multiple stages of hematopoiesis.
AB  - PTPN11, which encodes the tyrosine phosphatase SHP2, is mutated in approximately
      35% of patients with juvenile myelomonocytic leukemia (JMML) and at a lower
      incidence in other neoplasms. To model JMML pathogenesis, we generated knockin
      mice that conditionally express the leukemia-associated mutant Ptpn11(D61Y).
      Expression of Ptpn11(D61Y) in all hematopoietic cells evokes a fatal
      myeloproliferative disorder (MPD), featuring leukocytosis, anemia,
      hepatosplenomegaly, and factor-independent colony formation by bone marrow (BM)
      and spleen cells. The Lin(-)Sca1(+)cKit(+) (LSK) compartment is expanded and
      "right-shifted," accompanied by increased stem cell factor (SCF)-evoked colony
      formation and Erk and Akt activation. However, repopulating activity is decreased
      in diseased mice, and mice that do engraft with Ptpn11(D61Y) stem cells fail to
      develop MPD. Ptpn11(D61Y) common myeloid progenitors (CMPs) and granulocyte
      monocyte progenitors (GMPs) produce cytokine-independent colonies in a cell
      autonomous manner and demonstrate elevated Erk and Stat5 activation in response
      to granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation.
      Ptpn11(D61Y) megakaryocyte-erythrocyte progenitors (MEPs) yield increased numbers
      of erythrocyte burst-forming units (BFU-Es), but MEPs and erythrocyte-committed
      progenitors (EPs) produce fewer erythrocyte colony-forming units (CFU-Es),
      indicating defective erythroid differentiation. Our studies provide a mouse model
      for Ptpn11-evoked MPD and show that this disease results from cell-autonomous and
      distinct lineage-specific effects of mutant Ptpn11 on multiple stages of
      hematopoiesis.

PMID- 19179470
TI  - C7 is expressed on endothelial cells as a trap for the assembling terminal
      complement complex and may exert anti-inflammatory function.
AB  - We describe a novel localization of C7 as a membrane-bound molecule on
      endothelial cells (ECs). Data obtained by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE), Western blot analysis, Northern blot analysis,
      and mass spectrometry revealed that membrane-associated C7 (mC7) was
      indistinguishable from soluble C7 and was associated with vimentin on the cell
      surface. mC7 interacted with the other late complement components to form
      membrane-bound TCC (mTCC). Unlike the soluble SC5b-9, mTCC failed to stimulate
      ECs to express adhesion molecules, to secrete IL-8, and to induce albumin leakage
      through a monolayer of ECs, and more importantly protected ECs from the
      proinflammatory effect of SC5b-9. Our data disclose the possibility of a novel
      role of mC7 that acts as a trap for the late complement components to control
      excessive inflammation induced by SC5b-9.

PMID- 19179469
TI  - CBFbeta is critical for AML1-ETO and TEL-AML1 activity.
AB  - AML1-ETO and TEL-AML1 are chimeric proteins resulting from the t(8;21)(q22;q22)
      in acute myeloid leukemia, and the t(12;21)(p13;q22) in pre-B-cell leukemia,
      respectively. The Runt domain of AML1 in both proteins mediates DNA binding and
      heterodimerization with the core binding factor beta (CBFbeta) subunit. To
      determine whether CBFbeta is required for AML1-ETO and TEL-AML1 activity, we
      introduced amino acid substitutions into the Runt domain that disrupt
      heterodimerization with CBFbeta but not DNA binding. We show that CBFbeta
      contributes to AML1-ETO's inhibition of granulocyte differentiation, is essential
      for its ability to enhance the clonogenic potential of primary mouse bone marrow
      cells, and is indispensable for its cooperativity with the activated receptor
      tyrosine kinase TEL-PDGFbetaR in generating acute myeloid leukemia in mice.
      Similarly, CBFbeta is essential for TEL-AML1's ability to promote self-renewal of
      B cell precursors in vitro. These studies validate the Runt domain/CBFbeta
      interaction as a therapeutic target in core binding factor leukemias.

PMID- 19179471
TI  - CTLA-4 on alloreactive CD4 T cells interacts with recipient CD80/86 to promote
      tolerance.
AB  - Although the inhibitory receptor CTLA-4 (CD152) has been implicated in peripheral
      CD4 T-cell tolerance, its mechanism of action remains poorly defined. We analyzed
      mechanisms of CD4 cell tolerance in a model of tolerance induction involving
      establishment of mixed hematopoietic chimerism in recipients of fully MHC
      mismatched allogeneic bone marrow cells with anti-CD154 mAb. Animals lacking CD80
      and CD86 failed to achieve chimerism. We detected no T cell-intrinsic requirement
      for CD28 for chimerism induction. However, a CD4 T cell-intrinsic signal through
      CTLA-4 was shown to be essential within the first 48 hours of exposure to
      alloantigen for the establishment of tolerance and mixed chimerism. This signal
      must be provided by a recipient CD80/86(+) non-T-cell population. Donor CD80/86
      expression was insufficient to achieve tolerance. Together, our findings
      demonstrate a surprising role for interactions of CTLA-4 expressed by
      alloreactive peripheral CD4 T cells with CD80/86 on recipient antigen-presenting
      cells (APCs) in the induction of early tolerance, suggesting a 3-cell tolerance
      model involving directly alloreactive CD4 cells, donor antigen-expressing bone
      marrow cells, and recipient antigen-presenting cells. This tolerance is
      independent of regulatory T cells and culminates in the deletion of directly
      alloreactive CD4 T cells.

PMID- 19179472
TI  - Megakaryocyte-derived microvesicles, please stand up!

PMID- 19179473
TI  - Bone marrow cells can manipulate healing.

PMID- 19179474
TI  - The hunting of the Snrk.

PMID- 19179475
TI  - Trisomy 13: prevalence and clinicopathologic correlates of another potentially
      lenalidomide-sensitive cytogenetic abnormality.

PMID- 19179476
TI  - Intravenous administration of mesenchymal stem cells genetically modified with
      extracellular superoxide dismutase improves survival in irradiated mice.

PMID- 19179477
TI  - Elevated expression of the leukemia-associated antigen SSX2IP predicts survival
      in acute myeloid leukemia patients who lack detectable cytogenetic
      rearrangements.

PMID- 19179478
TI  - B cells versus T cells as primary barrier to hematopoietic engraftment in
      allosensitized recipients.

PMID- 19179479
TI  - Gonadotropin-releasing hormone and protein kinase C signaling to ERK:
      spatiotemporal regulation of ERK by docking domains and dual-specificity
      phosphatases.
AB  - Activated ERK translocates to the nucleus to regulate transcription.
      Spatiotemporal aspects of this response dictate biological consequences and are
      influenced by dual-specificity phosphatases (DUSPs) that can scaffold and
      dephosphorylate ERK. In HeLa cells, GnRH causes transient and protein kinase C
      (PKC)-dependent ERK activation, but termination mechanisms are unknown. We now
      explore DUSP roles using short inhibitory RNA to knock down endogenous ERK,
      adenoviruses to express GnRH receptors and add-back ERK2-GFP, and automated
      microscopy to monitor ERK location and activation. GnRH caused rapid and
      transient increases in dual phosphorylated ERK2 (ppERK2) and nuclear to
      cytoplasmic ERK2-green fluorescent protein (GFP) ratio, whereas responses to a
      PKC-activating phorbol ester were more sustained. In cells expressing D319N ERK2
      GFP (D319N mutation impairs docking-domain-dependent binding to DUSPs), GnRH
      caused more sustained increases in ppERK2 and nuclear to cytoplasmic ERK2-GFP
      ratio and also had more pronounced effects on Egr-1 luciferase (a transcriptional
      reporter for ERK activation). Cycloheximide caused more sustained effects of GnRH
      and phorbol ester on ppERK, suggesting termination by nuclear-inducible DUSPs.
      GnRH also increased expression of nuclear-inducible DUSP1 and -4, but their
      knockdown did not alter GnRH-mediated ERK signaling. Screening a short inhibitory
      RNA library targeting 16 DUSPs (nuclear-inducible DUSPs, cytoplasmic ERK MAPK
      phosphatases, c-Jun N-terminal kinase/p38 MAPK phosphatases, and atypical DUSPs)
      revealed GnRH effects to be influenced by DUSPs 5, 9, 10, 16, and 3 (i.e. by each
      DUSP class). Thus, GnRH-mediated ERK responses (like PKC-mediated ERK responses)
      are dependent on protein neosynthesis and docking-domain-dependent binding, but
      for GnRH activation (unlike PKC activation), this does not reflect dependence on
      nuclear-inducible DUSPs. Termination of these GnRH effects is apparently
      dependent upon a preexisting rapid turnover protein.

PMID- 19179480
TI  - Agonist-independent interactions between beta-arrestins and mutant vasopressin
      type II receptors associated with nephrogenic syndrome of inappropriate
      antidiuresis.
AB  - Nephrogenic syndrome of inappropriate antidiuresis is a recently identified
      genetic disease first described in two unrelated male infants with severe
      symptomatic hyponatremia. Despite undetectable arginine vasopressin levels,
      patients have inappropriately concentrated urine resulting in hyponatremia,
      hypoosmolality, and natriuresis. It was found that each infant had a different
      mutation of the vasopressin type II receptor (V2R) at codon 137 where arginine
      was converted to cysteine or leucine (R137C or R137L), resulting in constitutive
      signaling. Interestingly, a missense mutation at the same codon, converting
      arginine to histidine (R137H), leads to the opposite disease phenotype with a
      loss of the kidney's ability to concentrate urine resulting in nephrogenic
      diabetes insipidus. This mutation is associated with impaired signaling, although
      whether this is predominantly due to impaired trafficking to the plasma membrane,
      agonist-independent internalization, or G protein uncoupling is currently
      unclear. Using bioluminescence resonance energy transfer and confocal microscopy,
      we demonstrate that both V2R-R137C and V2R-R137L mutants interact with beta
      arrestins in an agonist-independent manner resulting in dynamin-dependent
      internalization. This phenotype is similar to that observed for V2R-R137H, which
      is intriguing considering that it is accompanied by constitutive rather than
      impaired signaling. Consequently, it would seem that agonist-independent
      internalization per se is unlikely to be the major determinant of impaired V2R
      R137H signaling. Our findings indicate that the V2R-R137C and V2R-R137L mutants
      traffic considerably more efficiently to the plasma membrane than V2R-R137H,
      identifying this as a potentially important mutation-dependent difference
      affecting V2R function.

PMID- 19179481
TI  - cAMP-dependent posttranscriptional regulation of steroidogenic acute regulatory
      (STAR) protein by the zinc finger protein ZFP36L1/TIS11b.
AB  - Star is expressed in steroidogenic cells as 3.5- and 1.6-kb transcripts that
      differ only in their 3'-untranslated regions (3'-UTR). In mouse MA10 testis and Y
      1 adrenal lines, Br-cAMP preferentially stimulates 3.5-kb mRNA. ACTH is similarly
      selective in primary bovine adrenocortical cells. The 3.5-kb form harbors AU-rich
      elements (AURE) in the extended 3'-UTR, which enhance turnover. After peak
      stimulation of 3.5-kb mRNA, degradation is seen. Star mRNA turnover is enhanced
      by the zinc finger protein ZFP36L1/TIS11b, which binds to UAUUUAUU repeats in the
      extended 3'-UTR. TIS11b is rapidly stimulated in each cell type in parallel with
      Star mRNA. Cotransfection of TIS11b selectively decreases cytomegalovirus
      promoted Star mRNA and luciferase-Star 3'-UTR reporters harboring the extended 3'
      UTR. Direct complex formation was demonstrated between TIS11b and the extended 3'
      UTR of the 3.5-kb Star. AURE mutations revealed that TIS11b-mediated
      destabilization required the first two UAUUUAUU motifs. HuR, which also binds
      AURE, did not affect Star expression. Targeted small interfering RNA knockdown of
      TIS11b specifically enhanced stimulation of 3.5-kb Star mRNA in bovine
      adrenocortical cells, MA-10, and Y-1 cells but did not affect the reversals seen
      after peak stimulation. Direct transfection of Star mRNA demonstrated that Br
      cAMP stimulated a selective turnover of 3.5-kb mRNA independent of AURE, which
      may correspond to these reversal processes. Steroidogenic acute regulatory (STAR)
      protein induction was halved by TIS11b knockdown, concomitant with decreased
      cholesterol metabolism. TIS11b suppression of 3.5-kb mRNA is therefore
      surprisingly coupled to enhanced Star translation leading to increased
      cholesterol metabolism.

PMID- 19179482
TI  - DISP3, a sterol-sensing domain-containing protein that links thyroid hormone
      action and cholesterol metabolism.
AB  - In the body, the brain is the most cholesterol-rich organ. Despite this,
      remarkably little is known about the mechanisms in the brain that regulate
      cholesterol homeostasis. Due to the blood-brain barrier, plasma lipoproteins are
      unable to traverse, and instead cholesterol must be synthesized de novo from
      within the central nervous system. Thyroid hormone receptors, activated in
      response to thyroid hormone (T(3)), are known to modulate the level of serum
      cholesterol via complex regulatory pathways. By screening for T(3)-regulated
      genes we have identified Disp3, a sterol-sensing domain-containing protein that
      is related to the Dispatched family of proteins. Analysis by RT-PCR and
      immunohistochemistry demonstrated that DISP3 is predominately expressed in
      specific cell types of the brain, retina, and testis. Using the model of
      hyperthyroidism in vivo, we observed the modulation of Disp3 expression in the
      retina. Furthermore, in vitro analysis of Disp3 expression in cells treated with
      T(3) revealed both positive and negative regulation. DISP3 localizes within the
      endoplasmic reticulum and was further found to colocalize with cholesterol.
      Ectopic expression of DISP3 in fibroblasts resulted in elevated cholesterol
      levels combined with an altered cholesterol distribution. Given that DISP3 is
      highly expressed in Purkinje cells, hippocampal neurons, and retinal ganglion
      cells and that its overexpression results in increased cholesterol levels, it is
      tempting to postulate that DISP3 may contribute to cholesterol homeostasis in
      neural cell types. Taken together, we propose that DISP3 represents a new
      molecular link between thyroid hormone and cholesterol metabolism.

PMID- 19179483
TI  - Down-regulation of hepatic HNF4alpha gene expression during hyperinsulinemia via
      SREBPs.
AB  - Mutations in the coding region of hepatocyte nuclear factor 4alpha (HNF4alpha),
      and its upstream promoter (P2) that drives expression in the pancreas, are known
      to lead to maturity-onset diabetes of the young 1 (MODY1). HNF4alpha also
      controls gluconeogenesis and lipid metabolism in the liver, where the proximal
      promoter (P1) predominates. However, very little is known about the role of
      hepatic HNF4alpha in diabetes. Here, we examine the expression of hepatic
      HNF4alpha in two diabetic mouse models, db/db mice (type 2, insulin resistant)
      and streptozotocin-treated mice (type 1, insulin deficient). We found that the
      level of HNF4alpha protein and mRNA was decreased in the liver of db/db mice but
      increased in streptozotocin-treated mice. Because insulin increases the activity
      of sterol regulatory element-binding proteins (SREBP)-1c and -2, we also examined
      the effect of SREBPs on hepatic HNF4alpha gene expression and found that, like
      insulin, ectopic expression of SREBPs decreases the level of hepatic HNF4alpha
      protein and mRNA both in vitro in primary hepatocytes and in vivo in the liver of
      C57BL/6 mice. Finally, we use gel shift, chromatin immunoprecipitation, small
      interfering RNA, and reporter gene analysis to show that SREBP2 binds the human
      HNF4alpha P1 promoter and negatively regulates its expression. These data
      indicate that hyperinsulinemia down-regulates HNF4alpha in the liver through the
      up-regulation of SREBPs, thereby establishing a link between these two critical
      transcription factor pathways that regulate lipid and glucose metabolism in the
      liver. These findings also provide new insights into diabetes-associated
      complications such as fatty liver disease.

PMID- 19179484
TI  - Biologic lung volume reduction in advanced upper lobe emphysema: phase 2 results.
AB  - RATIONALE: Biologic lung volume reduction (BioLVR) is a new endobronchial
      treatment for advanced emphysema that reduces lung volume through tissue
      remodeling. OBJECTIVES: Assess the safety and therapeutic dose of BioLVR hydrogel
      in upper lobe predominant emphysema. METHODS: Open-labeled, multicenter phase 2
      dose-ranging studies were performed with BioLVR hydrogel administered to eight
      subsegmental sites (four in each upper lobe) involving: (1) low-dose treatment (n
      = 28) with 10 ml per site (LD); and (2) high-dose treatment (n = 22) with 20 ml
      per site (HD). Safety was assessed by the incidence of serious medical
      complications. Efficacy was assessed by change from baseline in pulmonary
      function tests, dyspnea score, 6-minute walk distance, and health-related quality
      of life. MEASUREMENTS AND MAIN RESULTS: After treatment there were no deaths and
      four serious treatment-related complications. A reduction in residual volume to
      TLC ratio at 12 weeks (primary efficacy outcome) was achieved with both LD (-6.4
      +/- 9.3%; P = 0.002) and HD (-5.5 +/- 9.4%; P = 0.028) treatments. Improvements
      in pulmonary function in HD (6 mo: DeltaFEV(1) = +15.6%; P = 0.002; DeltaFVC =
      +9.1%; P = 0.034) were greater than in LD patients (6 mo: DeltaFEV(1) = +6.7%; P
      = 0.021; DeltaFVC = +5.1%; P = 0.139). LD- and HD-treated groups both
      demonstrated improved symptom scores and health-related quality of life.
      CONCLUSIONS: BioLVR improves physiology and functional outcomes up to 6 months
      with an acceptable safety profile in upper lobe predominant emphysema. Overall
      improvement was greater and responses more durable with 20 ml per site than 10 ml
      per site dosing. Clinical trial registered with www.clinicaltrials.gov (NCT
      00435253 and NCT 00515164).

PMID- 19179485
TI  - Shortened telomeres in circulating leukocytes of patients with chronic
      obstructive pulmonary disease.
AB  - RATIONALE: Telomere length is considered a marker for biological aging. Chronic
      obstructive pulmonary disease (COPD) may be associated with premature aging.
      OBJECTIVES: To test the hypothesis that patients with COPD experience accelerated
      telomere shortening and that inflammation is linked to this process. METHODS: We
      measured telomere length, using a quantitative polymerase chain reaction-based
      method, and plasma levels of various cytokines in 136 patients with COPD, 113 age
      and sex-matched smokers, and 42 nonsmokers with normal lung function.
      MEASUREMENTS AND MAIN RESULTS: Median (range) telomere length ratio was
      significantly lower in patients with COPD (0.57 [0.23-1.18]) than in control
      smokers (0.79 [0.34-1.58]) or nonsmokers (0.85 [0.38-1.55]) (P < 0.001). The
      difference remained highly significant when using logistic regression analysis
      adjusted for age, sex, and tobacco exposure. Both females and males with COPD had
      shorter telomere length than same-sex control subjects. Telomere length was
      related to age in patients and control subjects but was shorter in patients than
      in control subjects in all age groups. No relationship was found between telomere
      length and tobacco exposure in patients or control subjects, with no difference
      between control smokers and nonsmokers. In patients with COPD, telomere length
      was related to PaO2 (P < 0.001) and PaCO2 (P < 0.001) but not to lung function
      parameters or the BODE Index. Patients with COPD also had elevated plasma levels
      of various cytokines, interleukin-6 correlating negatively with telomere length
      (P < 0.001). CONCLUSIONS: Given that in vivo telomere length reflects cellular
      turnover and exposure to oxidative and inflammatory damage, our data support
      accelerated aging in COPD.

PMID- 19179486
TI  - Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica.
AB  - RATIONALE: Maternal vitamin D intake during pregnancy has been inversely
      associated with asthma symptoms in early childhood. However, no study has
      examined the relationship between measured vitamin D levels and markers of asthma
      severity in childhood. OBJECTIVES: To determine the relationship between measured
      vitamin D levels and both markers of asthma severity and allergy in childhood.
      METHODS: We examined the relation between 25-hydroxyvitamin D levels (the major
      circulating form of vitamin D) and markers of allergy and asthma severity in a
      cross-sectional study of 616 Costa Rican children between the ages of 6 and 14
      years. Linear, logistic, and negative binomial regressions were used for the
      univariate and multivariate analyses. MEASUREMENTS AND MAIN RESULTS: Of the 616
      children with asthma, 175 (28%) had insufficient levels of vitamin D (<30 ng/ml).
      In multivariate linear regression models, vitamin D levels were significantly and
      inversely associated with total IgE and eosinophil count. In multivariate
      logistic regression models, a log(10) unit increase in vitamin D levels was
      associated with reduced odds of any hospitalization in the previous year (odds
      ratio [OR], 0.05; 95% confidence interval [CI], 0.004-0.71; P = 0.03), any use of
      antiinflammatory medications in the previous year (OR, 0.18; 95% CI, 0.05-0.67; P
      = 0.01), and increased airway responsiveness (a < or =8.58-mumol provocative dose
      of methacholine producing a 20% fall in baseline FEV(1) [OR, 0.15; 95% CI, 0.024
      0.97; P = 0.05]). CONCLUSIONS: Our results suggest that vitamin D insufficiency
      is relatively frequent in an equatorial population of children with asthma. In
      these children, lower vitamin D levels are associated with increased markers of
      allergy and asthma severity.

PMID- 19179487
TI  - Bacteria challenge in smoke-exposed mice exacerbates inflammation and skews the
      inflammatory profile.
AB  - RATIONALE: The pathogenesis of chronic obstructive pulmonary disease is
      associated with acute episodes of bacterial exacerbations. The most commonly
      isolated bacteria during episodes of exacerbation is nontypeable Haemophilus
      influenzae (NTHI). OBJECTIVES: In this study, we investigated the in vivo
      consequences of cigarette smoke exposure on the inflammatory response to an NTHI
      challenge. METHODS: C57BL/6 and BALB/c mice were exposed to cigarette smoke for 8
      weeks and subsequently challenged intranasally with NTHI. MEASUREMENTS AND MAIN
      RESULTS: We observed increased pulmonary inflammation and lung damage in
      cigarette smoke-exposed NTHI-challenged mice as compared with control NTHI
      challenged mice. Furthermore, although NTHI challenge in control mice was marked
      by increases in tumor necrosis factor-alpha, IL-6, MIP-2, and KC/GROalpha, NTHI
      challenge in cigarette smoke-exposed mice led to a prominent up-regulation of a
      different subset of inflammatory mediators, most notably MCP-1, -3, and -5, IP
      10, and MIP-1gamma. This skewed inflammatory mediator expression was also
      observed after ex vivo NTHI stimulation of alveolar macrophages, signifying their
      importance to this altered response. Importantly, corticosteroids attenuated
      inflammation after NTHI challenge in both cigarette smoke-exposed and control
      mice; however, this was associated with significantly increased bacterial burden.
      CONCLUSIONS: Collectively, these data suggest that cigarette smoke exacerbates
      the inflammatory response to a bacterial challenge via skewed inflammatory
      mediator expression.

PMID- 19179488
TI  - Serum CC-chemokine ligand 18 concentration predicts outcome in idiopathic
      pulmonary fibrosis.
AB  - RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with
      a poor prognosis. There is great effort to find predictors of outcome. Conclusive
      data for any serum biomarker are lacking. We have recently documented that serum
      CCL18 concentrations correlate with the course of pulmonary function data in
      patients with pulmonary fibrosis of various causes. OBJECTIVES: To test the value
      of serum CCL18 concentrations in IPF, we included 72 patients in a prospective
      study. METHODS: IPF was defined according to the ATS/ERS criteria. Serum CCL18
      concentrations were measured by a commercially available ELISA. Patients were
      followed for 24 months. Pulmonary function tests were performed at least every 6
      months. MEASUREMENTS AND MAIN RESULTS: Baseline serum CCL18 concentrations
      predicted the change in TLC and FVC at the 6-month follow-up. Receiver operating
      characteristics (ROC) revealed a significant relation between survival and
      baseline CCL18 concentrations. By ROC analysis, the cutoff value with the highest
      diagnostic accuracy was defined as 150 ng/ml (sensitivity, 0.83; specificity,
      0.77). There was a significantly higher mortality in patients with serum CCL18
      concentrations above 150 ng/ml (P < 0.0001). The hazard proportional ratio
      adjusted for age, sex, and baseline pulmonary function data was 8.0. There was a
      higher incidence of disease progression in the group with high serum CCL18
      concentrations. CONCLUSIONS: Our data demonstrate that serum CCL18 concentrations
      have a predictive value in IPF and may be a useful tool in the clinical
      management of patients with IPF and in clinical trials.

PMID- 19179489
TI  - Resolution of allergic inflammation and airway hyperreactivity is dependent upon
      disruption of the T1/ST2-IL-33 pathway.
AB  - RATIONALE: Although there have been numerous studies on the development of
      allergen-induced inflammation, the mechanisms leading to resolution of
      inflammation remain poorly understood. This represents an important consideration
      because failure to resolve allergen driven inflammation potentially leads to
      irreversible airway remodeling, characteristic of chronic asthma. OBJECTIVES: We
      investigated the resolution of allergic inflammation and identified the factors
      responsible. METHODS: BALB/c and C57BL/6 mice were sensitized to ovalbumin and
      challenged through the airways to induce allergic inflammation. Mice were
      analyzed at 24 hours and 7 days after the final challenge. MEASUREMENTS AND MAIN
      RESULTS: Airway hyperreactivity (AHR) and increased mucus production were present
      7 days after the cessation of allergen challenge in BALB/c mice. Persisting AHR
      correlated with the continued presence of Th2 cells but not eosinophils in the
      lungs. The role of Th2 cells in maintaining AHR was confirmed using blocking
      antibodies against T1/ST2, IL-4, and IL-13 during the resolution period.
      Moreover, AHR in the "Th1 type" C57BL/6 mouse strain was resolved 1 week after
      allergen challenge, concomitant with clearance of Th2 cells from the lung.
      Expression of the T1/ST2 ligand, IL-33, also correlated with maintenance of AHR.
      CONCLUSIONS: We have used blockade of Th2 function and strain differences to show
      for the first time that resolution of allergic inflammation and AHR may be
      dependent on the T1/ST2-IL-33 pathway and the presence of Th2 cells, suggesting
      they are necessary not only for the development of an allergic response but also
      for its maintenance.

PMID- 19179490
TI  - Vitamin D as supplementary treatment for tuberculosis: a double-blind,
      randomized, placebo-controlled trial.
AB  - RATIONALE: Vitamin D has been shown to be involved in the host immune response
      toward Mycobacterium tuberculosis. OBJECTIVES: To test whether vitamin D
      supplementation of patients with tuberculosis (TB) improved clinical outcome and
      reduced mortality. METHODS: We conducted a randomized, double-blind, placebo
      controlled trial in TB clinics at a demographic surveillance site in Guinea
      Bissau. We included 365 adult patients with TB starting antituberculosis
      treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU
      of cholecalciferol or placebo at inclusion and again 5 and 8 months after the
      start of treatment. MEASUREMENTS AND MAIN RESULTS: The primary outcome was
      reduction in a clinical severity score (TBscore) for all patients with pulmonary
      TB. The secondary outcome was 12-month mortality. No serious adverse effects were
      reported; mild hypercalcemia was rare and present in both arms. Reduction in
      TBscore and sputum smear conversion rates did not differ among patients treated
      with vitamin D or placebo. Overall mortality was 15% (54 of 365) at 1 year of
      follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178
      for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131
      of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV
      1+2. CONCLUSIONS: Vitamin D does not improve clinical outcome among patients with
      TB and the trial showed no overall effect on mortality in patients with TB; it is
      possible that the dose used was insufficient. Clinical trial registered with
      www.controlled-trials.com/isrctn (ISRCTN35212132).

PMID- 19179491
TI  - Inducing a magnetic monopole with topological surface States.
AB  - Existence of the magnetic monopole is compatible with the fundamental laws of
      nature; however, this elusive particle has yet to be detected experimentally. We
      show theoretically that an electric charge near a topological surface state
      induces an image magnetic monopole charge due to the topological magneto-electric
      effect. The magnetic field generated by the image magnetic monopole may be
      experimentally measured, and the inverse square law of the field dependence can
      be determined quantitatively. We propose that this effect can be used to
      experimentally realize a gas of quantum particles carrying fractional statistics,
      consisting of the bound states of the electric charge and the image magnetic
      monopole charge.

PMID- 19179492
TI  - Zircon dating of oceanic crustal accretion.
AB  - Most of Earth's present-day crust formed at mid-ocean ridges. High-precision
      uranium-lead dating of zircons in gabbros from the Vema Fracture Zone on the Mid
      Atlantic Ridge reveals that the crust there grew in a highly regular pattern
      characterized by shallow melt delivery. Combined with results from previous
      dating studies, this finding suggests that two distinct modes of crustal
      accretion occur along slow-spreading ridges. Individual samples record a zircon
      date range of 90,000 to 235,000 years, which is interpreted to reflect the time
      scale of zircon crystallization in oceanic plutonic rocks.

PMID- 19179493
TI  - The role of fingerprints in the coding of tactile information probed with a
      biomimetic sensor.
AB  - In humans, the tactile perception of fine textures (spatial scale <200
      micrometers) is mediated by skin vibrations generated as the finger scans the
      surface. To establish the relationship between texture characteristics and
      subcutaneous vibrations, a biomimetic tactile sensor has been designed whose
      dimensions match those of the fingertip. When the sensor surface is patterned
      with parallel ridges mimicking the fingerprints, the spectrum of vibrations
      elicited by randomly textured substrates is dominated by one frequency set by the
      ratio of the scanning speed to the interridge distance. For human touch, this
      frequency falls within the optimal range of sensitivity of Pacinian afferents,
      which mediate the coding of fine textures. Thus, fingerprints may perform
      spectral selection and amplification of tactile information that facilitate its
      processing by specific mechanoreceptors.

PMID- 19179495
TI  - U.S.-China S&T at 30.

PMID- 19179494
TI  - A role for RNAi in the selective correction of DNA methylation defects.
AB  - DNA methylation is essential for silencing transposable elements and some genes
      in higher eukaryotes, which suggests that this modification must be tightly
      controlled. However, accidental changes in DNA methylation can be transmitted
      through mitosis (as in cancer) or meiosis, leading to epiallelic variation. We
      demonstrated the existence of an efficient mechanism that protects against
      transgenerational loss of DNA methylation in Arabidopsis. Remethylation is
      specific to the subset of heavily methylated repeats that are targeted by the RNA
      interference (RNAi) machinery. This process does not spread into flanking
      regions, is usually progressive over several generations, and faithfully restores
      wild-type methylation over target sequences in an RNAi-dependent manner. Our
      findings suggest an important role for RNAi in protecting genomes against long
      term epigenetic defects.

PMID- 19179496
TI  - Biotechnology. Celebration and concern over U.S. trial of embryonic stem cells.

PMID- 19179497
TI  - Human evolution. Early start for human art? Ochre may revise timeline.

PMID- 19179498
TI  - Research funding. European science not as intense as hoped.

PMID- 19179499
TI  - Archaeology. Iraq museum may reopen amid controversy.

PMID- 19179500
TI  - U.S. budget. A stimulus for science.

PMID- 19179501
TI  - Informal education. Report calls for fresh look at what happens outside school.

PMID- 19179502
TI  - Neuroscience. Fingerprints enhance the sense of touch.

PMID- 19179503
TI  - Plant genetics. How sorghum withstands heat and drought.

PMID- 19179504
TI  - Social sciences. Seeds of discontent.

PMID- 19179505
TI  - Social sciences. DOD funds new views on conflict with its first Minerva grants.

PMID- 19179506
TI  - Astronomy. Beset by delays, U.S. astronomers ponder a better 'to do' list.

PMID- 19179507
TI  - Astronomy. Priorities nearer to home in need of better cost estimates.

PMID- 19179508
TI  - Cancer. HPV casts a wider shadow.

PMID- 19179509
TI  - Systems politics and political systems.

PMID- 19179510
TI  - Scientists not immune to partisanship.

PMID- 19179511
TI  - Law and science not mutually exclusive.

PMID- 19179512
TI  - Credit for coauthors.

PMID- 19179513
TI  - Comment on "Arsenic (III) fuels anoxygenic photosynthesis in hot spring biofilms
      from Mono Lake, California".
AB  - Kulp et al. (Reports, 15 August 2008, p. 967) described a bacterium able to
      photosynthetically oxidize arsenite [As(III)] via arsenate [As(V)] reductase
      functioning in reverse. Based on their phylogenetic analysis of As(V) reductase,
      they proposed that this enzyme was responsible for the anaerobic oxidation of
      As(III) in the Archean. We challenge this proposition based on paleogeochemical,
      bioenergetic, and phylogenetic arguments.

PMID- 19179514
TI  - Physics. Learning and scientific reasoning.

PMID- 19179515
TI  - Cell biology. The force is with us.

PMID- 19179516
TI  - Materials science. Transforming graphene.

PMID- 19179517
TI  - Physics. An abnormal normal state.

PMID- 19179518
TI  - Plant science. Pores in place.

PMID- 19179519
TI  - Biochemistry. Unfolding the secrets of calmodulin.

PMID- 19179520
TI  - Ecology. The key to Pandora's box.

PMID- 19179521
TI  - Sudden death of entanglement.
AB  - A new development in the dynamical behavior of elementary quantum systems is the
      surprising discovery that correlation between two quantum units of information
      called qubits can be degraded by environmental noise in a way not seen previously
      in studies of dissipation. This new route for dissipation attacks quantum
      entanglement, the essential resource for quantum information as well as the
      central feature in the Einstein-Podolsky-Rosen so-called paradox and in
      discussions of the fate of Schrodinger's cat. The effect has been labeled ESD,
      which stands for early-stage disentanglement or, more frequently, entanglement
      sudden death. We review recent progress in studies focused on this phenomenon.

PMID- 19179522
TI  - Facile synthesis of AsP3.
AB  - The elements phosphorus and arsenic form tetrahedral P4 and As4 molecules, of
      which the former is a commodity chemical and the latter unstable. Previously,
      information on molecules of intermediate composition was limited to a
      spectroscopic study involving hot gas-phase mixtures of phosphorus and arsenic.
      The AsP3 molecule has yielded to chemical synthesis and was isolated in solid
      form as a pure substance with a melting point from 71 degrees to 73 degrees C.
      Physical properties and spectroscopic characterization data for AsP3 are
      described, and its structure was determined as a ligand in a coordination
      complex. Soluble in organic solvents, AsP3 represents an attractive starting
      point for any synthesis in which the target molecule or material contains an
      exact 1:3 ratio of arsenic to phosphorus.

PMID- 19179523
TI  - Revealing the maximum strength in nanotwinned copper.
AB  - The strength of polycrystalline materials increases with decreasing grain size.
      Below a critical size, smaller grains might lead to softening, as suggested by
      atomistic simulations. The strongest size should arise at a transition in
      deformation mechanism from lattice dislocation activities to grain boundary
      related processes. We investigated the maximum strength of nanotwinned copper
      samples with different twin thicknesses. We found that the strength increases
      with decreasing twin thickness, reaching a maximum at 15 nanometers, followed by
      a softening at smaller values that is accompanied by enhanced strain hardening
      and tensile ductility. The strongest twin thickness originates from a transition
      in the yielding mechanism from the slip transfer across twin boundaries to the
      activity of preexisting easy dislocation sources.

PMID- 19179524
TI  - Control of graphene's properties by reversible hydrogenation: evidence for
      graphane.
AB  - Although graphite is known as one of the most chemically inert materials, we have
      found that graphene, a single atomic plane of graphite, can react with atomic
      hydrogen, which transforms this highly conductive zero-overlap semimetal into an
      insulator. Transmission electron microscopy reveals that the obtained graphene
      derivative (graphane) is crystalline and retains the hexagonal lattice, but its
      period becomes markedly shorter than that of graphene. The reaction with hydrogen
      is reversible, so that the original metallic state, the lattice spacing, and even
      the quantum Hall effect can be restored by annealing. Our work illustrates the
      concept of graphene as a robust atomic-scale scaffold on the basis of which new
      two-dimensional crystals with designed electronic and other properties can be
      created by attaching other atoms and molecules.

PMID- 19179525
TI  - Dynamical quorum sensing and synchronization in large populations of chemical
      oscillators.
AB  - Populations of certain unicellular organisms, such as suspensions of yeast in
      nutrient solutions, undergo transitions to coordinated activity with increasing
      cell density. The collective behavior is believed to arise through communication
      by chemical signaling via the extracellular solution. We studied large,
      heterogeneous populations of discrete chemical oscillators (approximately
      100,000) with well-defined kinetics to characterize two different types of
      density-dependent transitions to synchronized oscillatory behavior. For different
      chemical exchange rates between the oscillators and the surrounding solution,
      increasing oscillator density led to (i) the gradual synchronization of
      oscillatory activity, or (ii) the sudden "switching on" of synchronized
      oscillatory activity. We analyze the roles of oscillator density and exchange
      rate of signaling species in these transitions with a mathematical model of the
      interacting chemical oscillators.

PMID- 19179526
TI  - Single nanocrystals of platinum prepared by partial dissolution of Au-Pt
      nanoalloys.
AB  - Small metal nanoparticles that are also highly crystalline have the potential for
      showing enhanced catalytic activity. We describe the preparation of single
      nanocrystals of platinum that are 2 to 3 nanometers in diameter. These particles
      were generated and immobilized on spherical polyelectrolyte brushes consisting of
      a polystyrene core (diameter of approximately 100 nanometers) onto which long
      chains of a cationic polyelectrolyte were affixed. In a first step, a nanoalloy
      of gold and platinum (a solid solution) was generated within the layer of
      cationic polyelectrolyte chains. In a second step, the gold was slowly and
      selectively dissolved by cyanide ions in the presence of oxygen. Cryogenic
      transmission electron microscopy, wide-angle x-ray scattering, and high
      resolution transmission electron microscopy showed that the resulting platinum
      nanoparticles are faceted single crystals that remain embedded in the
      polyelectrolyte-chain layer. The composite systems of the core particles and the
      platinum single nanocrystals exhibit an excellent colloidal stability, as well as
      high catalytic activity in hydrogenation reactions in the aqueous phase.

PMID- 19179527
TI  - Cascadia tremor located near plate interface constrained by S minus P wave times.
AB  - Nonvolcanic tremor is difficult to locate because it does not produce impulsive
      phases identifiable across a seismic network. An alternative approach to
      identifying specific phases is to measure the lag between the S and P waves. We
      cross-correlate vertical and horizontal seismograms to reveal signals common to
      both, but with the horizontal delayed with respect to the vertical. This lagged
      correlation represents the time interval between vertical compressional waves and
      horizontal shear waves. Measurements of this interval, combined with location
      techniques, resolve the depth of tremor sources within +/-2 kilometers. For
      recent Cascadia tremor, the sources locate near or on the subducting slab
      interface. Strong correlations and steady S-P time differences imply that tremor
      consists of radiation from repeating sources.

PMID- 19179528
TI  - Divergent evolution of duplicate genes leads to genetic incompatibilities within
      A. thaliana.
AB  - Genetic incompatibilities resulting from interactions between two loci represent
      a potential source of postzygotic barriers and may be an important factor in
      evolution when they impair the outcome of interspecific crosses. We show that, in
      crosses between strains of the plant Arabidopsis thaliana, loci interact
      epistatically, controlling a recessive embryo lethality. This interaction is
      explained by divergent evolution occurring among paralogs of an essential
      duplicate gene, for which the functional copy is not located at the same locus in
      different accessions. These paralogs demonstrate genetic heterogeneity in their
      respective evolutionary trajectories, which results in widespread incompatibility
      among strains. Our data suggest that these passive mechanisms, gene duplication
      and extinction, could represent an important source of genetic incompatibilities
      across all taxa.

PMID- 19179529
TI  - Serotonin mediates behavioral gregarization underlying swarm formation in desert
      locusts.
AB  - Desert locusts, Schistocerca gregaria, show extreme phenotypic plasticity,
      transforming between a little-seen solitarious phase and the notorious swarming
      gregarious phase depending on population density. An essential tipping point in
      the process of swarm formation is the initial switch from strong mutual aversion
      in solitarious locusts to coherent group formation and greater activity in
      gregarious locusts. We show here that serotonin, an evolutionarily conserved
      mediator of neuronal plasticity, is responsible for this behavioral
      transformation, being both necessary if behavioral gregarization is to occur and
      sufficient to induce it. Our data demonstrate a neurochemical mechanism linking
      interactions between individuals to large-scale changes in population structure
      and the onset of mass migration.

PMID- 19179530
TI  - Survival from hypoxia in C. elegans by inactivation of aminoacyl-tRNA
      synthetases.
AB  - Hypoxia is important in a wide range of biological processes, such as animal
      hibernation and cell survival, and is particularly relevant in many diseases. The
      sensitivity of cells and organisms to hypoxic injury varies widely, but the
      molecular basis for this variation is incompletely understood. Using forward
      genetic screens in Caenorhabditis elegans, we isolated a hypoxia-resistant
      reduction-of-function mutant of rrt-1 that encodes an arginyl-transfer RNA (tRNA)
      synthetase, an enzyme essential for protein translation. Knockdown of rrt-1, and
      of most other genes encoding aminoacyl-tRNA synthetases, rescued animals from
      hypoxia-induced death, and the level of hypoxia resistance was inversely
      correlated with translation rate. The unfolded protein response was induced by
      hypoxia and was required for the hypoxia resistance of the reduction-of-function
      mutant of rrt-1. Thus, translational suppression produces hypoxia resistance, in
      part by reducing unfolded protein toxicity.

PMID- 19179531
TI  - Ligand-dependent equilibrium fluctuations of single calmodulin molecules.
AB  - Single-molecule force spectroscopy allows superb mechanical control of protein
      conformation. We used a custom-built low-drift atomic force microscope to observe
      mechanically induced conformational equilibrium fluctuations of single molecules
      of the eukaryotic calcium-dependent signal transducer calmodulin (CaM). From this
      data, the ligand dependence of the full energy landscape can be reconstructed. We
      find that calcium ions affect the folding kinetics of the individual CaM domains,
      whereas target peptides stabilize the already folded structure. Single-molecule
      data of full length CaM reveal that a wasp venom peptide binds noncooperatively
      to CaM with 2:1 stoichiometry, whereas a target enzyme peptide binds
      cooperatively with 1:1 stoichiometry. If mechanical load is applied directly to
      the target peptide, real-time binding/unbinding transitions can be observed.

PMID- 19179532
TI  - Stretching single talin rod molecules activates vinculin binding.
AB  - The molecular mechanism by which a mechanical stimulus is translated into a
      chemical response in biological systems is still unclear. We show that mechanical
      stretching of single cytoplasmic proteins can activate binding of other
      molecules. We used magnetic tweezers, total internal reflection fluorescence, and
      atomic force microscopy to investigate the effect of force on the interaction
      between talin, a protein that links liganded membrane integrins to the
      cytoskeleton, and vinculin, a focal adhesion protein that is activated by talin
      binding, leading to reorganization of the cytoskeleton. Application of
      physiologically relevant forces caused stretching of single talin rods that
      exposed cryptic binding sites for vinculin. Thus in the talin-vinculin system,
      molecular mechanotransduction can occur by protein binding after exposure of
      buried binding sites in the talin-vinculin system. Such protein stretching may be
      a more general mechanism for force transduction.

PMID- 19179533
TI  - Mechanically activated integrin switch controls alpha5beta1 function.
AB  - The cytoskeleton, integrin-mediated adhesion, and substrate stiffness control a
      common set of cell functions required for development and homeostasis that are
      often deranged in cancer. The connection between these mechanical elements and
      chemical signaling processes is not known. Here, we show that alpha(5)beta(1)
      integrin switches between relaxed and tensioned states in response to myosin II
      generated cytoskeletal force. Force combines with extracellular matrix stiffness
      to generate tension that triggers the integrin switch. This switch directly
      controls the alpha(5)beta(1)-fibronectin bond strength through engaging the
      synergy site in fibronectin and is required to generate signals through
      phosphorylation of focal adhesion kinase. In the context of tissues, this
      integrin switch connects cytoskeleton and extracellular matrix mechanics to
      adhesion-dependent motility and signaling pathways.

PMID- 19179534
TI  - A human telomerase holoenzyme protein required for Cajal body localization and
      telomere synthesis.
AB  - Telomerase is a ribonucleoprotein (RNP) complex that synthesizes telomere repeats
      in tissue progenitor cells and cancer cells. Active human telomerase consists of
      at least three principal subunits, including the telomerase reverse
      transcriptase, the telomerase RNA (TERC), and dyskerin. Here, we identify a
      holoenzyme subunit, TCAB1 (telomerase Cajal body protein 1), that is notably
      enriched in Cajal bodies, nuclear sites of RNP processing that are important for
      telomerase function. TCAB1 associates with active telomerase enzyme, established
      telomerase components, and small Cajal body RNAs that are involved in modifying
      splicing RNAs. Depletion of TCAB1 by using RNA interference prevents TERC from
      associating with Cajal bodies, disrupts telomerase-telomere association, and
      abrogates telomere synthesis by telomerase. Thus, TCAB1 controls telomerase
      trafficking and is required for telomere synthesis in human cancer cells.

PMID- 19179535
TI  - PAN1: a receptor-like protein that promotes polarization of an asymmetric cell
      division in maize.
AB  - Polarization of cell division is essential for eukaryotic development, but little
      is known about how this is accomplished in plants. The formation of stomatal
      complexes in maize involves the polarization of asymmetric subsidiary mother cell
      (SMC) divisions toward the adjacent guard mother cell (GMC), apparently under the
      influence of a GMC-derived signal. We found that the maize pan1 gene promotes the
      premitotic polarization of SMCs and encodes a leucine-rich repeat receptor-like
      protein that becomes localized in SMCs at sites of GMC contact. PAN1 has an
      inactive kinase domain but is required for the accumulation of a membrane
      associated phosphoprotein, suggesting a function for PAN1 in signal transduction.
      Our findings implicate PAN1 in the transmission of an extrinsic signal that
      polarizes asymmetric SMC divisions toward GMCs.

PMID- 19179538
TI  - Characterization of parabrachial subnuclei in mice with regard to salt tastants:
      possible independence of taste relay from visceral processing.
AB  - We examined whether salt taste and/or abdominal illness were dealt within
      different subnuclei in the parabrachial nucleus (PBN) in mice, using retrograde
      tracing methods and c-Fos-like immunoreactivity (FLI) detection procedures. Some
      PBN subnuclei have distinct functions and receive various sensory inputs from the
      nucleus of the solitary tract (NTS) and other areas and relay them to the higher
      order nuclei such as the thalamus. The afferent-dependent pattern of FLI has been
      investigated in the PBN. However, it is unclear in which PBN subnuclei the
      tastants induce c-Fos, or whether PBN subnuclei process taste inputs separately
      from other inputs, or integrate them. After the tracer injections into the
      thalamic taste relay, the retrograde labeled cells revealed the taste relay cells
      in the PBN at the boundary with the superior cerebellar peduncle of both the
      inner part of the external lateral subnucleus and the medial subnucleus and in
      the waist area. On the other hand, NaCl intake induced intense FLI in the dorsal
      lateral subnucleus, whereas LiCl intake yielded intense FLI in both the dorsal
      lateral subnucleus and the outer part of the external lateral subnucleus. Thus,
      the present findings that subnuclei relaying taste information to the thalamus do
      not yield FLI in response to salt taste and abdominal illness indicate that they
      lack FLI yielding pathways or that they are independent from the subnuclei
      processing salt taste and visceral information via c-Fos in mice.

PMID- 19179536
TI  - Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell
      differentiation.
AB  - Schwann cells develop from multipotent neural crest cells and form myelin sheaths
      around axons that allow rapid transmission of action potentials. Neuregulin
      signaling through the ErbB receptor regulates Schwann cell development; however,
      the downstream pathways are not fully defined. We find that mice lacking
      calcineurin B1 in the neural crest have defects in Schwann cell differentiation
      and myelination. Neuregulin addition to Schwann cell precursors initiates an
      increase in cytoplasmic Ca2+, which activates calcineurin and the downstream
      transcription factors NFATc3 and c4. Purification of NFAT protein complexes shows
      that Sox10 is an NFAT nuclear partner and synergizes with NFATc4 to activate
      Krox20, which regulates genes necessary for myelination. Our studies demonstrate
      that calcineurin and NFAT are essential for neuregulin and ErbB signaling, neural
      crest diversification, and differentiation of Schwann cells.

PMID- 19179539
TI  - Review: immigrants and health care access, quality, and cost.
AB  - Inadequate access and poor quality care for immigrants could have serious
      consequences for their health and that of the overall U.S. population. The
      authors conducted a systematic search for post-1996, population-based studies of
      immigrants and health care. Of the 1,559 articles identified, 67 met study
      criteria of which 77% examined access, 27% quality, and 6% cost. Noncitizens and
      their children were less likely to have health insurance and a regular source of
      care and had lower use than the U.S. born. The foreign born or non-English
      speakers were less satisfied and reported lower ratings and more discrimination.
      Immigrants incurred lower costs than the U.S. born, except emergency department
      expenditures for immigrant children. Policy solutions are needed to improve
      health care for immigrants and their children. Research is needed to elucidate
      immigrants' nonfinancial barriers, receipt of specific processes of care, cost of
      care, and health care experiences in nontraditional U.S. destinations.

PMID- 19179540
TI  - Expression profiling of the solute carrier gene family in the mouse brain.
AB  - The solute carrier (Slc) superfamily is a major group of membrane transport
      proteins present in mammalian cells. Although Slc transporters play essential and
      diverse roles in the central nervous system, the localization and function of the
      vast majority of Slc genes in the mammalian brain are largely unknown. Using high
      throughput in situ hybridization data generated by the Allen Brain Atlas, we
      systematically and quantitatively analyzed the spatial and cellular distribution
      of 307 Slc genes, which represent nearly 90% of presently known mouse Slc genes,
      in the adult C57BL/6J mouse brain. Our analysis showed that 252 (82%) of the 307
      Slc genes are present in the brain, and a large proportion of these genes were
      detected at low to moderate expression levels. Evaluation of 20 anatomical brain
      subdivisions demonstrated a comparable level of Slc gene complexity but
      significant difference in transcript enrichment. The distribution of the
      expressed Slc genes was diverse, ranging from near-ubiquitous to highly
      localized. Functional annotation in 20 brain regions, including the blood-brain
      and blood-cerebral spinal fluid (CSF) barriers, suggests major roles of Slc
      transporters in supporting brain energy utilization, neurotransmission, nutrient
      supply, and CSF production. Furthermore, hierarchical cluster analysis revealed
      intricate Slc expression patterns associated with neuroanatomical organization.
      Our studies also revealed Slc genes present within defined brain microstructures
      and described the putative cell types expressing individual Slc genes. These
      results provide a useful resource for investigators to explore the roles of Slc
      genes in neurophysiological and pathological processes.

PMID- 19179541
TI  - Permeability of the blood-brain barrier to a rhenacarborane.
AB  - The treatment of brain malignancies with boron neutron capture therapy depends on
      their ability to cross the blood-brain barrier (BBB). An especially promising
      class of boron-containing compounds is the rhenacarboranes that, if able to cross
      the BBB, could act as delivery vehicles as well as a source of boron. Here, we
      examined the ability of the 3-NO-3,3-kappa(2)-(2,2'
      N(2)C(10)H(6)(Me)[(CH(2))(7)(131)I]-4,4')-closo-3,1,2-ReC(2)B(9)H(11)
      (rhenacarborane) labeled with iodine-131 to be taken up into the bloodstream
      after subcutaneous administration and to cross the BBB. The (131)I-rhenacarborane
      was quickly absorbed from the injection site and reached a steady state in
      arterial serum of 2.59%/ml of the administered dose. Between 73 and 95% of the
      radioactivity in serum 6 h after administration represented intact (131)I
      rhenacarborane. Its octanol/buffer partition coefficient was 1.74, showing it to
      be lipophilic. Tissue/serum ratios for brain, lung, and liver showed classic
      patterns for a lipid-soluble substance with high levels immediately achieved and
      rapid redistribution. For brain, a steady state of approximately 0.107% of the
      administered dose/gram-brain was rapidly reached, and 71% of the radioactivity in
      brain 6 h after subcutaneous administration represented intact (131)I
      rhenacarborane. Steady-state values were 1.53 and 0.89% of the injected dose per
      gram for lung and liver, respectively. (131)I-Rhenacarborane was quickly effluxed
      from brain by a nonsaturable system after its injection into the lateral
      ventricle of the brain. In conclusion, these results show that a rhenacarborane
      was enzymatically resistant and able to cross the BBB by transmembrane diffusion
      and accumulate in brain in substantial amounts. This supports their use as
      therapeutic agents for targeting the central nervous system.

PMID- 19179542
TI  - Causal claims.

PMID- 19179543
TI  - The devil is in the details: testing educational interventions.

PMID- 19179544
TI  - A review of clinical trials of tai chi and qigong in older adults.
AB  - Initiation and maintenance of physical activity (PA) in older adults is of
      increasing concern as the benefits of PA have been shown to improve physical
      functioning, mood, weight, and cardiovascular risk factors. Meditative movement
      forms of PA, such as tai chi and qigong (TC & QG), are holistic in nature and
      have increased in popularity over the past few decades. Several randomized
      controlled trials have evaluated TC & QG interventions from multiple
      perspectives, specifically targeting older adults. The purpose of this report is
      to synthesize intervention studies targeting TC & QG and identify the physical
      and psychological health outcomes shown to be associated with TC & QG in
      community dwelling adults older than 55. Based on specific inclusion criteria, 36
      research reports with a total of 3,799 participants were included in this review.
      Five categories of study outcomes were identified, including falls and balance,
      physical function, cardiovascular disease, and psychological and additional
      disease-specific responses. Significant improvement in clusters of similar
      outcomes indicated interventions utilizing TC & QG may help older adults improve
      physical function and reduce blood pressure, fall risk, and depression and
      anxiety. Missing from the reviewed reports is a discussion of how spiritual
      exploration with meditative forms of PA, an important component of these movement
      activities, may contribute to successful aging.

PMID- 19179546
TI  - Characteristics of relapse after autologous stem-cell transplantation for
      follicular lymphoma: a long-term follow-up.
AB  - BACKGROUND: Pattern and outcome of disease recurrence after autologous stem-cell
      transplantation (autoSCT) for follicular lymphoma (FL) is not well known.
      PATIENTS AND METHODS: Relapse cases were identified from 241 consecutive patients
      autografted for disseminated untransformed FL from 1990 to 2002 in three
      institutions. Prognostic factors for relapse and outcome after relapse were
      analyzed by log-rank comparisons and Cox regression analyses. RESULTS: One
      hundred and three relapses occurred. The 10-year relapse probability was 47%.
      Median time from autoSCT to relapse was 20 (2-128) months. Only three relapses
      were observed later than 6 years posttransplant. Median survival after relapse
      was 8.3 years. Patients with disease recurrence within 1 year from transplant and
      those who had received autoSCT as second-line treatment had significantly reduced
      survival by multivariate analysis, whereas Follicular Lymphoma International
      Prognostic Index score, age, remission status at autoSCT, high-dose regimen, and
      ex vivo purging had no impact. CONCLUSIONS: FL recurrence after autoSCT follows a
      biphasic pattern with continuing relapse during the first 6 years and only few
      events thereafter. The prognosis after relapse is relatively good and appears to
      be comparable to that of disease recurrence after standard treatment. The
      situation is less favorable for patients who relapse within the first
      posttransplant year.

PMID- 19179545
TI  - The role of tumor cell-derived connective tissue growth factor (CTGF/CCN2) in
      pancreatic tumor growth.
AB  - Pancreatic cancer is highly aggressive and refractory to existing therapies.
      Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is
      thought to play a role in pancreatic tumor progression. However, CCN2 can be
      expressed in a variety of cell types, and the contribution of CCN2 derived from
      either tumor cells or stromal cells as it affects the growth of pancreatic tumors
      is unknown. Using genetic inhibition of CCN2, we have discovered that CCN2
      derived from tumor cells is a critical regulator of pancreatic tumor growth.
      Pancreatic tumor cells derived from CCN2 shRNA-expressing clones showed
      dramatically reduced growth in soft agar and when implanted s.c. We also observed
      a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with
      tumor volume measurements obtained by positron emission tomography imaging.
      Mechanistically, CCN2 protects cells from hypoxia-mediated apoptosis, providing
      an in vivo selection for tumor cells that express high levels of CCN2. We found
      that CCN2 expression and secretion was increased in hypoxic pancreatic tumor
      cells in vitro, and we observed colocalization of CCN2 and hypoxia in pancreatic
      tumor xenografts and clinical pancreatic adenocarcinomas. Furthermore, we found
      increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal
      cells surrounding the tumor, supporting our assertion that tumor cell-derived
      CCN2 is important for pancreatic tumor growth. Taken together, these data improve
      our understanding of the mechanisms responsible for pancreatic tumor growth and
      progression, and also indicate that CCN2 produced by tumor cells represents a
      viable therapeutic target for the treatment of pancreatic cancer.

PMID- 19179547
TI  - Clinical features and treatment outcomes of advanced stage primary hepatic
      angiosarcoma.
AB  - BACKGROUND: Primary hepatic angiosarcoma is a very rare malignancy with a poor
      prognosis. While surgical resection has been validated as curative choice, most
      cases are diagnosed too late for resection. Nonetheless, treatment protocols have
      not been established and also there are very few reports on the clinical features
      and treatment outcomes. PATIENTS AND METHODS: Among 11,939 patients diagnosed
      with primary hepatic tumors from January 1985 to December 2007 at two centers,
      five patients were diagnosed with primary hepatic angiosarcoma. We analyzed
      patients' demographics, tumor characteristics, treatment modality, and outcomes
      using imaging, serology, and pathology. RESULTS: All five patients were diagnosed
      at advanced stage with distant metastases. The most common symptom was abdominal
      pain. The levels of the tumor markers were within the normal range and
      serological tests were negative for hepatitis B and C viruses. Two of four
      patients who received chemotherapy died <3 months after diagnosis, but the other
      two patients survived >6 months. CONCLUSIONS: A combination of chemotherapy
      resulted in an improved outcome for two of four patients, suggesting the
      potential usefulness of palliative chemotherapy to improve survival. This case
      study may aid in planning chemotherapy for patients with advanced hepatic
      angiosarcoma.

PMID- 19179548
TI  - The importance of KRAS mutations and EGF61A>G polymorphism to the effect of
      cetuximab and irinotecan in metastatic colorectal cancer.
AB  - BACKGROUND: The effect of anti-epidermal growth factor receptor (EGFR) antibodies
      (mAb) in metastatic colorectal cancer seems limited to KRAS wild-type (wt)
      tumours, but still a major fraction of KRASwt patients are nonresponders and
      supplementary selection criteria are needed. We investigated methodological
      aspects of KRAS testing and the predictive and prognostic value of KRAS status
      combined with three EGFR-related gene polymorphisms [single-nucleotide
      polymorphisms (SNPs)] in patients treated with cetuximab and irinotecan. PATIENTS
      AND METHODS: The study included 71 patients referred to third-line cetuximab
      irinotecan. Blood samples were analysed for SNPs. KRAS analysis was carried out
      by sequencing analysis and quantitative PCR (DxS kit) in primary tumour and
      distant metastases. RESULTS: There was a clear correlation between KRAS status in
      primary tumours and metastasis. The DxS kit presented the highest sensitivity.
      Response was confined to KRASwt patients (40% response rate versus 0%, P < 0.1(
      3)), which translated into a significant difference in PFS. The EGF61A>G
      polymorphism showed relation to clinical outcome. A combined biomarker analysis
      showed a 19% progression rate in KRASwt-EGF61 homozygote patients and 60% in the
      EGF61A/G patients (P = 0.006) and a significant increase in overall survival
      (17.1 versus 5.9 months, log-rank, P = 0.002). CONCLUSION: The combined biomarker
      analysis maybe an attractive approach to selection of patients for third-line
      treatment including anti-EGFR mAbs.

PMID- 19179549
TI  - A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in
      adjuvant high-risk colon cancer (FNCLCC Accord02/FFCD9802).
AB  - BACKGROUND: This multicenter adjuvant phase III trial evaluated the addition of
      irinotecan to LV5FU2 in colon cancer patients at high risk of relapse. PATIENTS
      AND METHODS: A total of 400 patients with histologically proven primary colon
      cancer with postoperative N1 detected by occlusion/perforation or N2 were
      randomised to: A-LV5FU2 [leucovorin 200 mg/m(2), 2-h infusion, 5-fluorouracil (5
      FU) 400 mg/m(2) bolus, 600 mg/m(2) 22-h continuous infusion, days 1 and 2] or B
      LV5FU2 + IRI (irinotecan 180 mg/m(2) 90-min infusion day 1 + LV5FU2) fortnightly
      for 12 cycles. Primary end point was disease-free survival (DFS). RESULTS: Median
      follow-up was 63 months. Significantly more T4 tumours and 15 or more positive
      lymph nodes were observed in arm B. 5-FU relative dose intensity (RDI) was >0.80
      for 94% and 77% in arms A and B, respectively (P < 0.001). Irinotecan RDI was
      >0.80 for 70% patients. There were more grades 3 and 4 neutropenia in arm B (4%
      versus 28%, P < 0.001). The 3-year DFS was 60% [95% confidence interval (CI) 53%
      to 66%] and 51% (95% CI 44% to 58) in arms A and B, respectively. No difference
      was observed [hazard ratio (HR) = 1.12, 95% CI 0.85-1.47, P = 0.42] even when
      adjusted for prognostic factors (adjusted HR = 0.98, 95% CI 0.74-1.31, P = 0.92).
      The 5-year overall survival (OS) was 67% (95% CI 59% to 73%) and 61% (95% CI 53%
      to 67%) in arms A and B, respectively. CONCLUSION: Adjuvant LV5FU2 + IRI compared
      with LV5FU2 alone in patients at high risk of relapse showed no improvement in
      DFS and OS.

PMID- 19179550
TI  - Best choice of central venous insertion site for the prevention of catheter
      related complications in adult patients who need cancer therapy: a randomized
      trial.
AB  - BACKGROUND: Central venous access is extensively used in oncology, though
      practical information from randomized trials on the most convenient insertion
      modality and site is unavailable. METHODS: Four hundred and three patients
      eligible for receiving i.v. chemotherapy for solid tumors were randomly assigned
      to implantation of a single type of port (Bard Port, Bard Inc., Salt Lake City,
      UT), through a percutaneous landmark access to the internal jugular, a ultrasound
      (US)-guided access to the subclavian or a surgical cut-down access through the
      cephalic vein at the deltoid-pectoralis groove. Early and late complications were
      prospectively recorded until removal of the device, patient's death or ending of
      the study. RESULTS: Four hundred and one patients (99.9%) were assessable: 132
      with the internal jugular, 136 with the subclavian and 133 with the cephalic vein
      access. The median follow-up was 356.5 days (range 0-1087). No differences were
      found for early complication rate in the three groups {internal jugular: 0% [95%
      confidence interval (CI) 0.0% to 2.7%], subclavian: 0% (95% CI 0.0% to 2.7%),
      cephalic: 1.5% (95% CI 0.1% to 5.3%)}. US-guided subclavian insertion site had
      significantly lower failures (e.g. failed attempts to place the catheter in
      agreement with the original arm of randomization, P = 0.001). Infections occurred
      in one, three and one patients (internal jugular, subclavian and cephalic access,
      respectively, P = 0.464), whereas venous thrombosis was observed in 15, 8 and 11
      patients (P = 0.272). CONCLUSIONS: Central venous insertion modality and sites
      had no impact on either early or late complication rates, but US-guided
      subclavian insertion showed the lowest proportion of failures.

PMID- 19179551
TI  - Age and HER2 expression status affect MRI accuracy in predicting residual tumor
      extent after neo-adjuvant systemic treatment.
AB  - BACKGROUND: Although recent studies suggest high accuracy of breast magnetic
      resonance imaging (MRI) in predicting residual tumor extent after neo-adjuvant
      systemic treatment (NST), its use is still controversial. In this study, we aimed
      to identify predictive factors of MRI accuracy after NST to determine a subgroup
      of patients in whom the use of MRI provides best additional benefit. MATERIALS
      AND METHODS: Clinicopathologic and molecular profiles of breast cancer patients
      were investigated and their relationships with MRI accuracy were analyzed.
      RESULTS: From January 2006 to February 2008, 195 patients received NST and
      preoperative MRI. In overall, MRI predicted residual tumor extent with higher
      accuracy than ultrasonography. Triple-negative (TN) tumors showed highest
      correlation between MRI-measured and pathologic tumor size (r = 0.781) when
      compared with other subtypes. Multivariate analysis showed age and HER2
      expression status as independent factors predicting MRI accuracy. When patients
      were classified based on their age and HER2 status, relatively older patients
      (>45) with HER2-negative tumors showed highest MRI accuracy. This finding was
      further validated using an independent cohort of 63 consecutive patients.
      CONCLUSION: Age and HER2 status independently affected MRI accuracy after NST.
      This observation may guide more tailored approach in using MRI in breast cancer
      patients undergoing NST.

PMID- 19179552
TI  - Two mutations of BRCA2 gene at exon and splicing site in a woman who underwent
      oncogenetic counseling.
AB  - BACKGROUND: Although most BRCA sequence variants are clearly deleterious and
      unequivocally pathogenetic, several are still classified as variants of unknown
      significance. PATIENTS AND METHODS: We followed families undergoing oncogenetic
      counseling from risk identification to risk definition by genetic testing and
      risk management. RESULTS: We identified two germline mutations in the BRCA2 gene
      in a woman with breast and ovarian cancer. One sequence alteration was 859/G>A in
      exon 7 (V211I). The other second sequence alteration (IVS13-2A>T) affected the
      splicing site in intron 13. The latter alteration is not yet listed in the Breast
      Cancer Information Core database. RT-PCR resulted in transcription of a sequence
      lacking exon 7 and a subsequent anomalous stop codon in exon 9 thereby confirming
      altered messenger RNA (mRNA) maturation. Amplification of the mutation in intron
      13 resulted in transcription of a sequence lacking exon 14 and an anomalous stop
      codon in exon 15 thereby confirming altered mRNA maturation. Both mutations led
      to a truncated BRCA2 protein in its carboxy-terminal region. CONCLUSION: The two
      BRCA2 mutations identified affect mRNA splicing fidelity and play a pathogenetic
      role in breast and ovarian cancer.

PMID- 19179553
TI  - The impact of N-ratio in minimizing stage migration phenomenon in gastric cancer
      patients with insufficient number or level of lymph node retrieved: results from
      a Chinese mono-institutional study in 2159 patients.
AB  - BACKGROUND: Previous studies indicate that N-ratio has significant superiority in
      minimizing 'stage migration' for patients with >15 lymph nodes retrieved. Whether
      the result is applicable to patients with < or =15 lymph nodes retrieved is still
      in question. PATIENTS AND METHODS: Overall survival rates of 2159 gastric cancer
      patients who underwent radical resection were compared between patients with
      different number and level of lymph nodes retrieved according to pN
      [International Union Against Cancer (Union Internationale Contre le Cancer)/AJCC
      N stage], n (JGCA N stage) and rN (N-ratio) staging system. RESULTS: Patient
      number was significantly different between insufficient and sufficient number or
      level retrieved group in pN and n system, respectively, but not in rN system,
      while overall survival rates were not significantly different between those
      groups. The 5-year survival rates of patients with insufficient nodes retrieved
      were significantly lower than those with sufficient nodes retrieved in pN and n
      system, but not in rN system. The hazard risk for patients with insufficient
      nodes retrieved was significantly higher than that for patients with sufficient
      nodes retrieved in pN and n system, but not in rN system. CONCLUSION: The rN
      stage has more potential advantages in minimizing stage migration phenomenon for
      patients with insufficient number or level of lymph nodes retrieved.

PMID- 19179554
TI  - The role of immune suppression and HHV-8 in the increasing incidence of HIV
      associated multicentric Castleman's disease.
AB  - BACKGROUND: In HIV cohorts with access to highly active antiretroviral therapy
      (HAART), the incidence of Kaposi's sarcoma (KS) is falling; however, the
      incidence of multicentric Castleman's disease (MCD) in HIV has not previously
      been described. METHODS: The incidence of HIV-associated MCD was calculated from
      a prospective HIV database with 56 202 patient-years of follow-up and compared
      with KS. Univariate and multivariate analyses were carried out to identify
      factors associated with MCD. Plasma human herpesvirus (HHV)-8 DNA levels were
      measured in HIV-seropositive individuals with newly diagnosed MCD (n = 24), KS (n
      = 72), HIV-associated lymphoma (n = 74) and HIV-positive controls (n = 53).
      RESULTS: From 24 cases of HIV-associated MCD, the incidence measured 4.3/10,000
      patient-years [95% confidence interval (CI) 2.7-6.4]. The incidence in the pre
      HAART (1983-1996), early-HAART (1997-2001) and later HAART (2002-2007) eras were
      2.3 (95% CI 0.02-4.2), 2.8 (95% CI 0.9-6.5) and 8.3 (95% CI 4.6-12.6),
      respectively, representing a statistically significant increase over time (P <
      0.05). In contrast, from 1180 cases of KS, the incidence in this cohort decreased
      with time. Multivariate analysis demonstrated that a nadir CD4 count >200/mm(3),
      increased age, no previous HAART exposure and non-Caucasian ethnicity were all
      associated with an increased risk of MCD. Plasma HHV-8 DNA levels were higher in
      patients with newly diagnosed MCD than with KS, lymphomas or HIV-positive
      controls (Mann-Whitney U-test, P < 0.0001). CONCLUSIONS: The incidence of HIV
      associated MCD is increasing. It appears to occur more frequently in older HIV
      positive individuals with well-preserved immune function.

PMID- 19179555
TI  - Soft tissue sarcomas of the trunk wall (STS-TW): a study of 343 patients from the
      French Sarcoma Group (FSG) database.
AB  - BACKGROUND: Soft tissue sarcomas of the trunk wall (STS-TW) are usually studied
      together with soft tissue sarcomas of other locations. We report a study on STS
      TW forming part of the French Sarcoma Group database. PATIENTS AND METHODS: Three
      hundred and forty-three adults were included. We carried out univariate and
      multivariate analysis for overall survival (OS), metastasis-free survival (MFS)
      and local recurrence-free survival (LRFS). RESULTS: Tumor locations were as
      follows: thoracic wall, 82.5%; abdominal wall, 12.3% and pelvic wall, 5.2%.
      Median tumor size was 6.0 cm. The most frequent tumor types were unclassified
      sarcoma (27.7%) and myogenic sarcoma (19.2%). A total of 44.6% of cases were
      grade 3. In all, 21.9% of patients had a previous medical history of radiotherapy
      (PHR). Median follow-up was 7.6 years. The 5-year OS, MFS and LRFS rates were
      60.4%, 68.9% and 58.4%, respectively. Multivariate analysis retained PHR and
      grade for predicting LRFS and PHR, size and grade as prognostic factors of MFS.
      Factors influencing OS were age, size, PHR, depth, grade and surgical margins.
      The predictive factors of incomplete response were PHR, size and T3. CONCLUSIONS:
      Our results suggest similar classical prognostic factors as compared with
      sarcomas of other locations. However, a separate analysis of STS-TW revealed a
      significant poor prognosis subgroup of patients with PHR.

PMID- 19179556
TI  - Sequential therapy for the locally advanced larynx and hypopharynx cancer
      subgroup in TAX 324: survival, surgery, and organ preservation.
AB  - BACKGROUND: Locally advanced laryngeal and hypopharyngeal cancers (LHC) represent
      a group of cancers for which surgery, laryngectomy-free survival (LFS), overall
      survival (OS), and progression-free survival (PFS) are clinically meaningful end
      points. PATIENTS AND METHODS: These outcomes were analyzed in the subgroup of
      assessable LHC patients enrolled in TAX 324, a phase III trial of sequential
      therapy comparing docetaxel plus cisplatin and fluorouracil (TPF) against
      cisplatin and fluorouracil (PF), followed by chemoradiotherapy. RESULTS: Among
      501 patients enrolled in TAX 324, 166 had LHC (TPF, n = 90; PF, n = 76). Patient
      characteristics were similar between subgroups. Median OS for TPF was 59 months
      [95% confidence interval (CI): 31-not reached] versus 24 months (95% CI: 13-42)
      for PF [hazard ratio (HR) for death: 0.62; 95% CI: 0.41-0.94; P = 0.024]. Median
      PFS for TPF was 21 months (95% CI: 12-59) versus 11 months (95% CI: 8-14) for PF
      (HR: 0.66; 95% CI: 0.45-0.97; P = 0.032). Among operable patients (TPF, n = 67;
      PF, n = 56), LFS was significantly greater with TPF (HR: 0.59; 95% CI: 0.37-0.95;
      P = 0.030). Three-year LFS with TPF was 52% versus 32% for PF. Fewer TPF patients
      had surgery (22% versus 42%; P = 0.030). CONCLUSIONS: In locally advanced LHC,
      sequential therapy with induction TPF significantly improved survival and PFS
      versus PF. Among operable patients, TPF also significantly improved LFS and PFS.
      These results support the use of sequential TPF followed by carboplatin
      chemoradiotherapy as a treatment option for organ preservation or to improve
      survival in locally advanced LHC.

PMID- 19179557
TI  - Combining carboplatin and etoposide in docetaxel-pretreated patients with
      castration-resistant prostate cancer: a prospective study evaluating also
      neuroendocrine features.
AB  - BACKGROUND: There is currently no standard treatment for patients with castration
      resistant prostate cancer (CRPC) whose disease progresses after docetaxel-based
      chemotherapy. The purpose of this study was to prospectively assess the
      anticancer activity and tolerance of the carboplatin-etoposide combination in
      this setting while evaluating neuroendocrine (NE) features. PATIENTS AND METHODS:
      Patients with CRPC and metastases who experienced failure after first-line
      docetaxel-based chemotherapy were treated with carboplatin (area under the curve
      5, day 1) and etoposide (80 mg/m(2)/day from days 1 to 3), repeated every 3
      weeks. The association between serum chromogranin A (CgA), neuron-specific
      enolase (NSE), prostate-specific antigen-doubling time (PSADT), and treatment
      efficacy was studied. RESULTS: Forty patients with CRPC who had received
      docetaxel with (n = 20) or without (n = 20) estramustine received the carboplatin
      etoposide combination as second-line chemotherapy. A prostate-specific antigen
      (PSA) response defined as a PSA decline > or =50% was achieved in nine patients
      (23%). Median progression-free survival (PFS) was 2.1 months (range 0.6-9.6) and
      median overall survival was 19 months (range 2.1-27.7). Pain response was
      achieved in 15 (53%) of 28 assessable patients. Toxicity, including mainly grades
      3-4 anaemia (25%) and febrile neutropenia in only 2% of patients, was manageable.
      Baseline CgA, NSE, or PSADT were not significant predictors for response or PFS.
      The PSA response rates were 18% and 31% in patients with normal and elevated
      serum CgA, respectively. It was 25% and 20%, respectively, in patients with
      normal and elevated serum NSE. CONCLUSIONS: Combining carboplatin and etoposide
      as second-line chemotherapy in patients with CRPC is active and well tolerated in
      spite of a limited PFS. Activity was observed in CRPC with and without NE
      features.

PMID- 19179558
TI  - Single-agent lapatinib for HER2-overexpressing advanced or metastatic breast
      cancer that progressed on first- or second-line trastuzumab-containing regimens.
AB  - BACKGROUND: This phase II study evaluated the efficacy and safety of lapatinib in
      patients with human epidermal growth factor receptor 2 (HER2)-positive advanced
      or metastatic breast cancer that progressed during prior trastuzumab therapy.
      PATIENTS AND METHODS: Women with stage IIIB/IV HER2-overexpressing breast cancer
      were treated with single-agent lapatinib 1250 or 1500 mg once daily after
      protocol amendment. Tumor response according to RECIST was assessed every 8
      weeks. HER2 expression was assessed in tumor tissue by immunohistochemistry and
      FISH. RESULTS: Seventy-eight patients were enrolled in the study. Investigator
      and independent review response rates [complete response (CR) or partial response
      (PR)] were 7.7% and 5.1%, and clinical benefit rates (CR, PR, or stable disease
      for >or=24 weeks) were 14.1% and 9.0%, respectively. Median time to progression
      was 15.3 weeks by independent review, and median overall survival was 79 weeks.
      The most common treatment-related adverse events were rash (47%), diarrhea (46%),
      nausea (31%), and fatigue (18%). CONCLUSIONS: Single-agent lapatinib has clinical
      activity with manageable toxic effects in HER2-overexpressing breast cancer that
      progressed on trastuzumab-containing therapy. Studies of lapatinib-based
      combination regimens with chemotherapy and other targeted therapies in metastatic
      and earlier stages of breast cancer are warranted.

PMID- 19179559
TI  - Genetic and physiological analysis of tomato fruit weight and composition:
      influence of carbon availability on QTL detection.
AB  - Throughout tomato domestication, a large increase in fruit size was associated
      with a loss of dry matter and sugar contents. This study aims to dissect the
      contributions of genetic variation and the physiological processes underlying the
      relationships between fruit growth and the accumulation of dry matter and sugars.
      Fruit quality traits and physiological parameters were measured on 20
      introgression lines derived from the introgression of Solanum chmielewskii into
      S. lycopersicum, under high (HL, unpruned trusses) and low (LL, trusses pruned to
      one fruit) fruit load conditions. Inter- and intra-genotypic correlations among
      traits were estimated and quantitative trait loci (QTL) for size, composition,
      and physiological traits were mapped. LL increased almost all traits, but the
      response of sugar content was genotype-dependent, involving either dilution
      effects or differences in carbon allocation to sugars. Genotype x fruit load
      interactions were significant for most traits and only 30% of the QTL were stable
      under both fruit loads. Many QTL for fresh weight and cell or seed numbers co
      localized. Eleven clusters of QTL for fresh weight and dry matter or sugar
      content were detected, eight with opposite allele effects and three with negative
      effects. Two genotypic antagonistic relationships, between fresh weight and dry
      matter content and between cell number and cell size, were significant only under
      HL; the second could be interpreted as a competition for carbohydrates among
      cells. The role of cuticular conductance, fruit transpiration or cracking in the
      relationship between fruit fresh weight and composition was also emphasized at
      the genetic and physiological levels.

PMID- 19179560
TI  - Abstracts of the 4th Annual Perioperative Medicine Summit 2009. February 5-7,
      2009. Miami Beach, Florida, USA..

PMID- 19179604
TI  - Proepithelin regulates prostate cancer cell biology by promoting cell growth,
      migration, and anchorage-independent growth.
AB  - The growth factor proepithelin has recently emerged as an important regulator of
      transformation in several physiological and pathological systems. In this study,
      we determined the biological roles of proepithelin in prostate cancer cells using
      purified human recombinant proepithelin as well as proepithelin-depletion
      strategies. Proepithelin promoted the migration of androgen-dependent and 
      independent human prostate cancer cells; androgen-independent DU145 cells were
      the more responsive. In these cells, proepithelin additionally stimulated wound
      closure, invasion, and promotion of cell growth in vitro. These effects required
      the activation of both the Akt and mitogen-activated protein kinase pathways. We
      have analyzed proepithelin expression levels in different available prostate
      cancer microarray studies using the Oncomine database and found a statistically
      significant increase in proepithelin mRNA expression levels in prostate cancers
      compared with nonneoplastic controls. Notably, depletion of endogenous
      proepithelin by siRNA and antisense strategies impaired the ability of DU145
      cells to grow and migrate after serum withdrawal and inhibited anchorage
      independent growth. Our results provide the first evidence for a role of
      proepithelin in stimulating the migration, invasion, proliferation, and anchorage
      independent growth of prostate cancer cells. This study supports the hypothesis
      that proepithelin may play a critical role as an autocrine growth factor in the
      establishment and initial progression of prostate cancer. Furthermore,
      proepithelin may prove to be a useful clinical marker for the diagnosis of
      prostate tumors.

PMID- 19179605
TI  - Aortic carboxypeptidase-like protein is expressed in fibrotic human lung and its
      absence protects against bleomycin-induced lung fibrosis.
AB  - The pathological hallmarks of idiopathic pulmonary fibrosis include proliferating
      fibroblasts and myofibroblasts, as well as excessive collagen matrix deposition.
      In addition, both myofibroblast contraction and remodeling of the collagen-rich
      matrix contribute to the abnormal structure and function of the fibrotic lung.
      Little is known, however, about collagen-associated proteins that promote
      fibroblast and myofibroblast retention, as well as the proliferation of these
      cells on the extracellular matrix. In this study, we demonstrate that aortic
      carboxypeptidase-like protein (ACLP), a collagen-associated protein with a
      discoidin-like domain, is expressed at high levels in human fibrotic lung tissue
      and human fibroblasts, and that its expression increases markedly in the lungs of
      bleomycin-injured mice. Importantly, ACLP-deficient mice accumulated
      significantly fewer myofibroblasts and less collagen in the lung after bleomycin
      injury, as compared with wild-type controls, despite equivalent levels of
      bleomycin-induced inflammation. ACLP that is secreted by lung fibroblasts was
      retained on fibrillar collagen, and ACLP-deficient lung fibroblasts that were
      cultured on collagen exhibited changes in cell spreading, proliferation, and
      contraction of the collagen matrix. Finally, the addition of recombinant
      discoidin-like domain of ACLP to cultured ACLP-deficient lung fibroblasts
      restored cell spreading and increased the contraction of collagen gels.
      Therefore, both ACLP and its discoidin-like domain may be novel targets for anti
      myofibroblast-based therapies for the treatment of pulmonary fibrosis.

PMID- 19179606
TI  - HMGA2 maintains oncogenic RAS-induced epithelial-mesenchymal transition in human
      pancreatic cancer cells.
AB  - Pancreatic cancer is a highly aggressive malignancy due to elevated mitotic
      activities and epithelial-mesenchymal transition (EMT). Oncogenic RAS and
      transforming growth factor-beta signaling are implicated in these malignant
      features. The mechanisms that underlie EMT need to be addressed since it promotes
      tissue invasion and metastasis. The high-mobility group A protein 2 (HMGA2) is a
      non-histone chromatin factor that is primarily expressed in undifferentiated
      tissues and tumors of mesenchymal origin. However, its role in EMT in pancreatic
      cancer is largely unknown. Here we report that HMGA2 is involved in EMT
      maintenance in human pancreatic cancer cells. Specific knockdown of HMGA2
      inhibited cell proliferation, leading to an epithelial-state transition that
      restores cell-cell contact due to E-cadherin up-regulation. Consistently, an
      inverse correlation between HMGA2-positive cells and E-cadherin-positive cells
      was found in cancer tissues. Inhibition of the RAS/MEK pathway also induced an
      epithelial transition, together with HMGA2 down-regulation. Transcriptional
      repressors of the E-cadherin gene, such as SNAIL, decreased after HMGA2 knockdown
      since HMGA2 directly activated the SNAlL gene promoter. The decrease of SNAIL
      after RAS/MEK inhibition was suppressed by HMGA2 overexpression. Further, let-7
      microRNA-mediated HMGA2 down-regulation had no effect on the prevention of the
      transformed phenotype in these cells. These data shed light on the importance of
      HMGA2 in reversibly maintaining EMT, suggesting that HMGA2 is a potential
      therapeutic target for the treatment of pancreatic cancer.

PMID- 19179607
TI  - Ribozyme-mediated targeting of IkappaBgamma inhibits melanoma invasion and
      metastasis.
AB  - IkappaBgamma is one member of a family of proteins that can inhibit the nuclear
      localization of nuclear factor-kappaB. However, the other specific functions of
      IkappaBgamma are still poorly understood, and its effects on tumor metastasis
      have not yet been characterized. We examined the consequences of targeting
      IkappaBgamma in melanoma cells using a hammerhead ribozyme. We developed stable
      transformant B16-F10 melanoma cell lines that express a ribozyme that targets
      mouse IkappaBgamma (IkappaBgamma-144-Rz). Tail-vein injection of B16-F10 cells
      that stably express IkappaBgamma-144-Rz into mice resulted in a significant
      reduction of the metastatic potential of these cells. IkappaBgamma-144-Rz
      expressing B16 cells were shown to have increased transcriptional activity of
      nuclear factor-kappaB. We then showed that IkappaBgamma-144-Rz-expressing cells
      demonstrated both reduced invasion and increased apoptosis, suggesting the
      existence of pathways through which IkappaBgamma promotes melanoma metastasis.
      Using gene expression profiling, we identified a differentially expressed gene
      set that is regulated by the stable suppression of IkappaBgamma that may
      participate in mediating its anti-metastatic effects; we also confirmed the
      altered expression levels of several of these genes by quantitative real time
      polymerase chain reaction. Plasmid-mediated expression of IkappaBgamma-144-Rz
      produced a significant inhibition of the metastatic progression of B16-F10 cells
      to the lung and resulted in significant anti-invasive and pro-apoptotic effects
      on murine Lewis lung carcinoma cells. Our results suggest a novel role for
      IkappaBgamma in promoting the metastatic progression of melanoma.

PMID- 19179608
TI  - Prolactin-growth factor crosstalk reduces mammary estrogen responsiveness despite
      elevated ERalpha expression.
AB  - Most breast cancers that occur in women express estrogen receptor alpha
      (ERalpha). However, a large subset of these cancers either does not initially
      respond to anti-estrogen therapy or develops resistance to such treatment
      modalities. One postulated mechanism of this failure is signaling cross talk
      between hormones and local growth factors. To examine these complex interactions
      in vivo, we assessed the effects of estrogen on transforming growth factor alpha
      (TGFalpha)- and prolactin (PRL)-induced mammary tumorigenesis in transgenic mice.
      Both PRL and estrogen reduced the latency of TGFalpha-induced oncogenesis,
      resulting in tumors that were variably ERalpha-positive, but were progesterone
      receptor-negative. However, despite elevated ERalpha levels in NRL-PRL/TGFalpha
      glands, tumor latency was not reduced with increasing estrogen levels, nor
      increased after ovariectomy. Furthermore, PRL and TGFalpha in combination blocked
      the mitogenic effects of estrogen, dramatically reduced progesterone receptor
      levels, and diminished ERalpha down-regulation in response to circulating
      estrogen levels, in contrast to the other genotypes. Notably, however, ductal
      morphology remained responsive to estrogen, indicating that TGFalpha and PRL in
      combination can inhibit some, but not all, estrogenic signals. Both in vitro and
      in vivo, PRL and TGFalpha cooperatively enhanced Akt phosphorylation, which is
      associated with endocrine resistance in human disease. These findings provide
      insight into the interactions of PRL with growth factors during mammary
      oncogenesis and suggest combinatorial approaches that may result in improved
      therapeutic efficacy.

PMID- 19179609
TI  - Valproic acid activates the PI3K/Akt/mTOR pathway in muscle and ameliorates
      pathology in a mouse model of Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy is a lethal neuromuscular disease that currently has
      no effective therapy. Transgenic overexpression of the alpha7 integrin in
      mdx/utrn(-/-) mice, a model of Duchenne muscular dystrophy ameliorates the
      disease. We have isolated and used alpha7(+/-) muscle cells expressing beta
      galactosidase, driven by the endogenous alpha7 promoter, to identify compounds
      that increase alpha7 integrin levels. Valproic acid (VPA) was found to enhance
      alpha7 integrin levels, induce muscle hypertrophy, and inhibit apoptosis in
      myotubes by activating the Akt/mTOR/p70S6K pathway. This activation of the Akt
      pathway occurs within 1 hour of treatment and is mediated by phosphatidylinositol
      3-OH kinase. To evaluate the potential use of VPA to treat muscular dystrophy,
      mdx/utrn(-/-) mice were injected with the drug. Treatment with VPA lowered
      collagen content and fibrosis, and decreased hind limb contractures. VPA-treated
      mice also had increased sarcolemmal integrity and decreased damage, decreased CD8
      positive inflammatory cells, and higher levels of activated Akt in their muscles.
      Thus, VPA has important biological effects that may be applicable for the
      treatment of muscular dystrophy.

PMID- 19179610
TI  - Ezetimibe is an inhibitor of tumor angiogenesis.
AB  - Epidemiological and preclinical observations have suggested a role for one or
      more products of the mevalonate/cholesterol biosynthesis pathway in the
      progression of prostate cancer. In this study, we used ezetimibe (Zetia), a
      specific, FDA-approved, cholesterol uptake-blocking drug, in combination with
      either a hyper- or hypocholesterolemic diet, to show that elevated circulating
      cholesterol levels promote, whereas a reduction in circulating cholesterol levels
      retard, the growth of human prostate cancer xenograft tumors in mice. Circulating
      cholesterol levels also modified tumor angiogenesis; higher cholesterol levels
      increased microvessel density and other indicators of vascularity. Consistent
      with these data, the reduction of cholesterol levels also increased the levels of
      the angiogenesis inhibitor thrombospondin-1 in the xenografts. Our results thus
      suggest that hypercholesterolemia directly accelerates the growth of prostate
      carcinomas, and that the pharmacological reduction of serum cholesterol levels
      may retard prostate cancer growth by inhibiting tumor angiogenesis.

PMID- 19179611
TI  - Dendritic cell-nerve clusters are sites of T cell proliferation in allergic
      airway inflammation.
AB  - Interactions between T cells and dendritic cells in the airway mucosa precede
      secondary immune responses to inhaled antigen. The purpose of this study was to
      identify the anatomical locations where dendritic cell-T cell interactions occur,
      resulting in T cells activation by dendritic cells. In a mouse model of allergic
      airway inflammation, we applied whole-mount immunohistology and confocal
      microscopy to visualize dendritic cells and T cells together with nerves,
      epithelium, and smooth muscle in three dimensions. Proliferating T cells were
      identified by the detection of the incorporation of the nucleotide analogue 5
      ethynyl-2'-deoxyuridine into the DNA. We developed a novel quantification method
      that enabled the accurate determination of cell-cell contacts in a semi-automated
      fashion. Dendritic cell-T cell interactions occurred beneath the smooth muscle
      layer, but not in the epithelium. Approximately 10% of the dendritic cells were
      contacted by nerves, and up to 4% of T cells formed clusters with these dendritic
      cells. T cells that were clustered with nerve-contacting dendritic cells
      proliferated only in the airways of mice with allergic inflammation but not in
      the airways of negative controls. Taken together, these results suggest that
      during the secondary immune response, sensory nerves influence dendritic cell
      driven T cell activation in the airway mucosa.

PMID- 19179612
TI  - Galectin-3 is critical for the development of the allergic inflammatory response
      in a mouse model of atopic dermatitis.
AB  - Galectin-3 belongs to a family of beta-galactoside-binding animal lectins
      expressed in several cell types, including epithelial and immune cells. To
      establish the role of galectin-3 in the development of allergic skin
      inflammation, we compared inflammatory skin responses of galectin-3-deficient
      (gal3(-/-)) and wild-type (gal3(+/+)) mice to epicutaneous sensitization with
      ovalbumin (OVA). OVA-treated gal3(-/-) mice exhibited markedly reduced epidermal
      thickening, lower eosinophil infiltration, and lower serum IgE levels compared
      with gal3(+/+) mice. The former evoked lower interleukin-4, but higher interferon
      gamma, mRNA expression at OVA-treated skin sites. Moreover, gal3(-/-) splenocytes
      from OVA-sensitized mice secreted more interleukin-12 compared with gal3(+/+)
      splenocytes. In addition, antigen presentation by gal3(-/-) dendritic cells to T
      cells in vitro were T helper cell (Th1)-polarized relative to presentation by
      gal3(+/+) dendritic cells. When exposed to OVA, recipients engrafted with T cells
      from gal3(-/-) OVA-specific T cell receptor transgenic mice developed
      significantly reduced dermatitis and a markedly lower Th2 response compared with
      recipients of comparable gal3(+/+) T cells. We conclude that galectin-3 is
      critical for the development of inflammatory Th2 responses to epicutaneously
      administered antigens; in its absence, mice develop a Th1-polarized response.
      This regulatory effect of galectin-3 on Th development is exerted at both the
      dendritic cell and T cell levels. Our studies suggest that galectin-3 may play an
      important role in the acute phase of human atopic dermatitis.

PMID- 19179613
TI  - Critical roles of lysosomal acid lipase in T cell development and function.
AB  - Lysosomal acid lipase (LAL) cleaves cholesteryl esters and triglycerides to
      generate free fatty acids and cholesterol in lysosomes. In LAL gene-knockout
      (lal(-/-)) mice, blockage of cholesteryl ester and triglyceride metabolism led to
      abnormal organization of the thymus and spleen, as well as neutral lipid
      accumulation in these organs. LAL deficiency impaired T cell development in the
      thymus. Peripheral T cells were reduced dramatically in lal(-/-) mice, due
      largely to increased apoptosis and decreased proliferation of lal(-/-) T cells in
      the thymus and peripheral compartments. These lal(-/-) T cells lost the ability
      to respond to T cell receptor stimulation, including reduced expression of cell
      surface receptor CD69, abolishment of T cell proliferation, and decreased
      expression of T lymphokines after stimulation by either anti-CD3 plus anti-CD28
      or phorbol-12-myristate-13-acetate and ionomycin. Differentiation of Th1 and Th2
      CD4(+) effector lymphocytes by T cell receptor stimulation was blocked in lal(-/
      ) mice. The ratio of CD4(+)CD25(+)FoxP3(+) Tregs to CD4(+) T cells was increased
      in lal(-/-) spleens. Bone marrow chimeras demonstrated retardation of T cell
      development and maturation in lal(-/-) mice due to defects in T cell precursors.
      Therefore, LAL, its downstream genes, and lipid mediators all play essential
      roles in development, homeostasis, and function of T cells. The altered
      development and function of lal(-/-) T cells contributes to disease formation in
      various organs during LAL deficiency.

PMID- 19179614
TI  - Aberrant heparan sulfate proteoglycan localization, despite normal exostosin, in
      central chondrosarcoma.
AB  - The tumor suppressor genes EXT1 and EXT2 are involved in the formation of
      multiple osteochondromas, which can progress to become secondary peripheral
      chondrosarcomas. The most common chondrosarcoma subtype is primary central
      chondrosarcoma, which occurs in the medullar cavity of bone. The EXT1/EXT2
      protein complex is involved in heparan sulfate proteoglycan (HSPG) biosynthesis,
      which is important for signal transduction of Indian hedgehog (IHH), WNT, and
      transforming growth factor (TGF)-beta. The role of EXT and its downstream targets
      in central chondrosarcomas is currently unknown. EXT1 and EXT2 were therefore
      evaluated in central chondrosarcomas at both the DNA and mRNA levels.
      Immunohistochemistry was used to assess HSPG (CD44v3 and SDC2), WNT (beta
      catenin), and TGF-beta (PAI-1 and phosphorylated Smad2) signaling, whereas IHH
      signaling was studied both by quantitative polymerase chain reaction and in
      vitro. mRNA levels of both EXT1 and EXT2 were normal in central chondrosarcomas;
      genomic alterations were absent in these regions and in 30 other HSPG-related
      genes. Although HSPGs were aberrantly located (CD44v3 in the Golgi and SDC2 in
      cytoplasm and nucleus), this was not caused by mutation. WNT signaling negatively
      correlated with increasing histological grade, whereas TGF-beta positively
      correlated with increasing histological grade. IHH signaling was active, and
      inhibition decreased cell viability in one of six cell lines. Our data suggest
      that, despite normal EXT in central chondrosarcomas, HSPGs and HSPG-dependent
      signaling are affected in both central and peripheral chondrosarcomas.

PMID- 19179616
TI  - Premature terminal differentiation and a reduction in specific proteases
      associated with loss of ABCA12 in Harlequin ichthyosis.
AB  - One of the primary functions of skin is to form a defensive barrier against
      external infections and water loss. Disrupted barrier function underlies the most
      severe and often lethal form of recessive congenital ichthyosis, harlequin
      ichthyosis (HI). HI is associated with mutations in the gene that encodes the ABC
      transporter protein, ABCA12. We have investigated the morphological and
      biochemical alterations associated with abnormal epidermal differentiation and
      barrier formation in HI epidermis. An in vitro model of HI skin using human
      keratinocytes retrovirally transduced with shRNA targeting ABCA12 in a three
      dimensional, organotypic co-culture (OTCC) system has also been developed. A
      robust reduction in ABCA12 expression had a dramatic effect on keratinocyte
      differentiation and morphology comparable with that observed in HI skin,
      including a thicker epidermis and abnormal lipid content with a reduction in
      nonpolar lipids. As seen in HI epidermis, proteins that are normally expressed in
      late differentiation were highly dysregulated in the ABCA12-ablated OTCC system.
      These proteins were expressed in the stratum basale and also in the stratum
      spinosum, indicative of a premature terminal differentiation phenotype.
      Expression of the proteases kallikrein 5 and cathepsin D was dramatically reduced
      in both HI epidermis and the OTCC model. These data suggest that ABCA12 is a key
      molecule in regulating keratinocyte differentiation and transporting specific
      proteases associated with desquamation.

PMID- 19179615
TI  - Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of
      head and neck squamous cell carcinoma.
AB  - Small noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in
      every tumor type examined. The importance of miRNAs as potential cancer
      prognostic indicators is underscored by their involvement in the regulation of
      basic cellular processes such as cell proliferation, differentiation, and
      apoptosis. In this study, miRNA expression profiles of head and neck squamous
      cell carcinoma (HNSCC) tumor and adjacent normal tissue were examined by
      microarray analysis and validated by quantitative TaqMan real-time polymerase
      chain reaction. Using TaqMan real-time polymerase chain reaction we measured the
      quantitative associations between a subset of miRNAs identified on microarrays in
      primary tumors at diagnosis and cancer survival in a cohort of 104 HNSCC patients
      undergoing treatment with curative intent. The majority of miRNAs exhibiting
      altered expression in primary human HNSCC tumors (including miR-1, miR-133a, miR
      205, and let-7d) show lower expression levels relative to normal adjacent tissue.
      In contrast, hsa-miR-21 is frequently overexpressed in human HNSCC tumors. Using
      univariate and multivariable statistical models we show that low levels of hsa
      miR205 are significantly associated with loco-regional recurrence independent of
      disease severity at diagnosis and treatment. In addition, combined low levels of
      hsa-miR-205 and hsa-let-7d expression in HNSCC tumors are significantly
      associated with poor head and neck cancer survival Our results show that miRNA
      expression levels can be used as prognostic markers of head and neck cancer.

PMID- 19179617
TI  - Expression of major histocompatibility complex class II antigens in porcine
      leptospiral nephritis.
AB  - Class II major histocompatibility complex (MHCII) is required for the
      presentation of antigens to CD4 helper T cells. During nephritis, not only
      primary antigen presenting cells such as histiocytes and lymphocytes, but also
      cytokine-stimulated tubular epithelial cells express MHCII. Leptospirosis in
      fattening pigs is characterized by several degrees of nephritis, from absence of
      lesions to severe multifocal tubulo-interstitial inflammation. Renal tissue from
      20 8-month-old pigs with spontaneous nephritis and 6 control pigs without renal
      lesions were investigated for leptospirosis by indirect immunohistochemistry
      (IHC) and polymerase chain reaction (PCR). IHC for MHCII also was performed on
      renal samples. Serum samples were tested for different serovars of Leptospira
      interrogans. Control pigs were free of interstitial nephritis and negative for
      leptospirosis by all tests. In pigs with nephritis, serology was positive for
      serovar Pomona in 19/20 pigs. In 16 of these 19 pigs, leptospiral renal infection
      was confirmed by PCR and/or indirect IHC. Nephritic lesions were classified
      histologically into perivascular lymphocytic (4 pigs), lymphofollicular (6 pigs),
      lymphohistiocytic (8 pigs), and neutrophilic (2 pigs) pattern. MHCII expression
      by histiocytes and lymphocytes was observed in all lesions. Prominent MHCII
      expression in regenerating tubular epithelium was observed in lymphofollicular
      and lymphohistiocytic nephritis. No tubular colocalization between leptospiral
      and MHCII antigen was observed. Results suggest that during leptospiral
      nephritis, MHCII contributes to the intensity of the inflammatory response.
      Furthermore de novo MHCII expression in regenerating tubules may play a role in
      the defence mechanism against leptospiral tubular colonization.

PMID- 19179618
TI  - Interleukin-1beta contributes via nitric oxide to the upregulation and functional
      activity of the zinc transporter Zip14 (Slc39a14) in murine hepatocytes.
AB  - Zinc metabolism during chronic disease is dysregulated by inflammatory cytokines.
      Experiments with IL-6 knockout mice show that LPS regulates expression of the
      zinc transporter, Zip14, by a mechanism that is partially independent of IL-6.
      The LPS-induced model of sepsis may occur by a mechanism signaled by nitric oxide
      (NO) as a secondary messenger. To address the hypothesis that NO can modulate
      Zip14 expression, we treated primary hepatocytes from wild-type mice with the NO
      donor S-nitroso N-acetyl penicillamine (SNAP). After treatment with SNAP, steady
      state Zip14 mRNA levels displayed a maximal increase after 8 h and a concomitant
      increase in the transcriptional activity of the gene. Chromatin
      immunoprecipitation documented the kinetics of activator protein (AP)-1 and RNA
      polymerase II association with the Zip14 promoter after NO exposure, indicating a
      role of AP-1 in transcription of Zip14. We then stimulated the primary murine
      hepatocytes with IL-1beta, an LPS-induced proinflammatory cytokine and a potent
      activator of inducible NO synthase (iNOS) and NO production. In support of our
      hypothesis, IL-1beta treatment led to a threefold increase in Zip14 mRNA and
      enhanced zinc transport, as measured with a zinc fluorophore, in wild-type but
      not iNOS-/- hepatocytes. These data suggest that signaling pathways activated by
      NO are factors in the upregulation of Zip14, which in turn mediates hepatic zinc
      accumulation and hypozincemia during inflammation and sepsis.

PMID- 19179619
TI  - Very high aquaporin-1 facilitated water permeability in mouse gallbladder.
AB  - Water transport across gallbladder epithelium is driven by osmotic gradients
      generated from active salt absorption and secretion. Aquaporin (AQP) water
      channels have been proposed to facilitate transepithelial water transport in
      gallbladder and to modulate bile composition. We found strong AQP1
      immunofluorescence at the apical membrane of mouse gallbladder epithelium.
      Transepithelial osmotic water permeability (Pf) was measured in freshly isolated
      gallbladder sacs from the kinetics of luminal calcein self-quenching in response
      to an osmotic gradient. Pf was very high (0.12 cm/s) in gallbladders from wild
      type mice, cAMP independent, and independent of osmotic gradient size and
      direction. Although gallbladders from AQP1 knockout mice had similar size and
      morphology to those from wild-type mice, their Pf was reduced by approximately 10
      fold. Apical plasma membrane water permeability was greatly reduced in AQP1
      deficient gallbladders, as measured by cytoplasmic calcein quenching in
      perfluorocarbon-filled, inverted gallbladder sacs. However, neither bile
      osmolality nor bile salt concentration differed in gallbladders from wild-type
      vs. AQP1 knockout mice. Our data indicate constitutively high water permeability
      in mouse gallbladder epithelium involving transcellular water transport through
      AQP1. The similar bile salt concentration in gallbladders from AQP1 knockout mice
      argues against a physiologically important role for AQP1 in mouse gallbladder.

PMID- 19179621
TI  - Tissue factor-dependent coagulation contributes to alpha-naphthylisothiocyanate
      induced cholestatic liver injury in mice.
AB  - Separation of concentrated bile acids from hepatic parenchymal cells is a key
      function of the bile duct epithelial cells (BDECs) that form intrahepatic bile
      ducts. Using coimmunostaining, we found that tissue factor (TF), the principal
      activator of coagulation, colocalized with cytokeratin 19, a marker of BDECs in
      the adult mouse liver. BDEC injury induced by xenobiotics such as alpha
      naphthylisothiocyanate (ANIT) causes cholestasis, inflammation, and
      hepatocellular injury. We tested the hypothesis that acute ANIT-induced
      cholestatic hepatitis is associated with TF-dependent activation of coagulation
      and determined the role of TF in ANIT hepatotoxicity. Treatment of mice with ANIT
      (60 mg/kg) caused multifocal hepatic necrosis and significantly increased serum
      biomarkers of cholestasis and hepatic parenchymal cell injury. ANIT treatment
      also significantly increased liver TF expression and activity. ANIT-induced
      activation of the coagulation cascade was shown by increased plasma thrombin
      antithrombin levels and significant deposition of fibrin within the necrotic
      foci. ANIT-induced coagulation and liver injury were reduced in low-TF mice,
      which express 1% of normal TF levels. The results indicate that ANIT-induced
      liver injury is accompanied by TF-dependent activation of the coagulation cascade
      and that TF contributes to the progression of injury during acute cholestatic
      hepatitis.

PMID- 19179620
TI  - Delineating the signals by which repetitive deformation stimulates intestinal
      epithelial migration across fibronectin.
AB  - Repetitive strain stimulates intestinal epithelial migration across fibronectin
      via focal adhesion kinase (FAK), Src, and extracellular signal-related kinase
      (ERK) although how these signals act and interact remains unclear. We
      hypothesized that PI3K is central to this pathway. We subjected Caco-2 and
      intestinal epithelial cell-6 cells to 10 cycles/min deformation on flexible
      fibronectin-coated membranes, assayed migration by wound closure, and signaling
      by immunoblots. Strain stimulated PI3K, AKT, glycogen synthase kinase (GSK), and
      p38 phosphorylation. Blocking each kinase prevented strain stimulation of
      migration. Blocking PI3K prevented strain-stimulated ERK and p38 phosphorylation.
      Blocking AKT did not. Downstream, blocking PI3K, AKT, or ERK inhibited strain
      induced GSK-Ser9 phosphorylation. Upstream of AKT, reducing FAK or Rac1 by siRNA
      blocked strain-stimulated AKT phosphorylation, but inhibiting Src by PP2 or siRNA
      did not. Transfection with FAK point mutants at Tyr397, Tyr576/577, or Tyr925
      demonstrated that only FAK925 phosphorylation is required for strain-stimulated
      AKT phosphorylation. Myosin light chain activation by strain required FAK, Rac1,
      PI3K, AKT, GSK, and ERK but not Src or p38. Finally, blebbistatin, a nonmuscle
      myosin II inhibitor, blocked the motogenic effect of strain downstream of myosin
      light chain. Thus strain stimulates intestinal epithelial migration across
      fibronectin by a complex pathway including Src, FAK, Rac1, PI3K, AKT, GSK, ERK,
      p38, myosin light chain, and myosin II.

PMID- 19179622
TI  - Lysophosphatidyl choline modulates mechanosensitive L-type Ca2+ current in
      circular smooth muscle cells from human jejunum.
AB  - The L-type Ca2+ channel expressed in gastrointestinal smooth muscle is
      mechanosensitive. Direct membrane stretch and shear stress result in increased
      Ca2+ entry into the cell. The mechanism for mechanosensitivity is not known, and
      mechanosensitivity is not dependent on an intact cytoskeleton. The aim of this
      study was to determine whether L-type Ca2+ channel mechanosensitivity is
      dependent on tension in the lipid bilayer in human jejunal circular layer
      myocytes. Whole cell currents were recorded in the amphotericin-perforated-patch
      configuration, and lysophosphatidyl choline (LPC), lysophosphatidic acid (LPA),
      and choline were used to alter differentially the tension in the lipid bilayer.
      Shear stress (perfusion at 10 ml/min) was used to mechanostimulate L-type Ca2+
      channels. The increase in L-type Ca2+ current induced by shear stress was greater
      in the presence of LPC (large head-to-tail proportions), but not LPA or choline,
      than in the control perfusion. The increased peak Ca2+ current also did not
      return to baseline levels as in control conditions. Furthermore, steady-state
      inactivation kinetics were altered in the presence of LPC, leading to a change in
      window current. These findings suggest that changes in tension in the
      plasmalemmal membrane can be transmitted to the mechanosensitive L-type Ca2+
      channel, leading to altered activity and Ca2+ entry in the human jejunal circular
      layer myocyte.

PMID- 19179623
TI  - Secretory effects of a luminal bitter tastant and expressions of bitter taste
      receptors, T2Rs, in the human and rat large intestine.
AB  - Taste transduction molecules, such as Galpha(gust), and taste receptor families
      for bitter [taste receptor type 2 (T2R)], sweet, and umami, have previously been
      identified in taste buds and the gastrointestinal (GI) tract; however, their
      physiological functions in GI tissues are still unclear. Here, we investigated
      the physiological function and expression of T2R in human and rat large intestine
      using various physiological and molecular biological techniques. To study the
      physiological function of T2R, the effect of a bitter compound, 6-n-propyl-2
      thiouracil (6-PTU), on transepithelial ion transport was investigated using the
      Ussing chamber technique. In mucosal-submucosal preparations, mucosal 6-PTU
      evoked Cl(-) and HCO(3)(-) secretions in a concentration-dependent manner. In rat
      middle colon, levels of 6-PTU-evoked anion secretion were higher than in distal
      colon, but there was no such difference in human large intestine. The response to
      6-PTU was greatly reduced by piroxicam, but not by tetrodotoxin. Additionally,
      prostaglandin E(2) concentration-dependently potentiated the response to 6-PTU.
      Transcripts of multiple T2Rs (putative 6-PTU receptors) were detected in both
      human and rat colonic mucosa by RT-PCR. In conclusion, these results suggest that
      the T2R ligand, 6-PTU, evokes anion secretion, and such response is regulated by
      prostaglandins. This luminal bitter sensing mechanism may be important for host
      defense in the GI tract.

PMID- 19179624
TI  - Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons
      induced by noxious stimuli.
AB  - Lactobacillus species ingestion can decrease autonomic responses and spinal fiber
      discharge to nociceptive colorectal distension (CRD), even in the absence of
      inflammation. The present study aimed to determine whether dorsal root ganglion
      (DRG) somas could be a locus where the antinociceptive probiotic may have an
      effect. Healthy rats were fed with Lactobacillus reuteri or vehicle control for 9
      days whereupon they were anesthetized, and intermittent distal colonic CRD at 80
      mmHg distension was either performed for 1 h or not. The animals were immediately
      euthanized and patch-clamp recordings taken after isolation and overnight culture
      from those DRG that projected to the distal colon. CRD decreased the threshold
      for action potential generation and increased the number of spikes discharged
      during a standard depolarizing test stimulus, and this effect was blocked by
      prior probiotic ingestion. The increase in excitability was paralleled by an
      increase in DRG capacitance, which was not altered by Lactobacillus reuteri
      ingestion. CRD did not increase tissue weight or myeloperoxidase activity. We
      suggest that the effects of CRD may have been caused by activity-dependent
      neurotransmission between DRG somas. CRD evoked increases in action potential
      upstroke speed, which suggests that it may also have led to augmentation of
      sodium channel conductances. Probiotic ingestion may have interfered with this
      hypothetical mechanism since it blocked the effect of CRD on the action
      potential.

PMID- 19179626
TI  - Regulation of the proprotein convertase subtilisin/kexin type 9 in intestinal
      epithelial cells.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) posttranslationally
      promotes the degradation of the low-density lipoprotein receptor (LDLr) in
      hepatocytes and increases plasma LDL cholesterol. It is not clear, however,
      whether PCSK9 plays a role in the small intestine. Here, we characterized the
      patterns of variations of PCSK9 and LDLr in fully differentiated Caco-2/15 cells
      as a function of various potential effectors. Cholesterol (100 microM)
      solubilized in albumin or micelles significantly downregulated PCSK9 gene (30%,
      P<0.05) and protein expression (50%, P<0.05), surprisingly in concert with a
      decrease in LDLr protein levels (45%, P<0.05). Cells treated with 25
      hydroxycholesterol (50 microM) also displayed significant reduction in PCSK9 gene
      (37%, P<0.01) and protein (75% P<0.001) expression, whereas LDLr showed a
      decrease at the gene (30%, P<0.05) and protein (57%, P<0.01) levels,
      respectively. The amounts of PCSK9 mRNA and protein in Caco-2/15 cells were
      associated to the regulation of 3-hydroxy-3-methylglutaryl-CoA reductase and
      sterol regulatory element binding protein-2 (SREBP-2) that can transcriptionally
      activate PCSK9 via sterol-regulatory elements located in its proximal promoter
      region. On the other hand, depletion of cholesterol content by hydroxypropyl-beta
      cyclodextrin upregulated PCSK9 transcripts (20%, P<0.05) and protein mass (540%,
      P<0.001), in parallel with SREBP-2 protein levels. The addition of bile acids
      (BA) taurocholate and deoxycholate to the apical culture medium lowered PCSK9
      gene expression (25%, P<0.01) and raised PCSK9 protein expression (30%, P<0.01),
      respectively, probably via the modulation of farnesoid X receptor. Furthermore,
      unconjugated and conjugated BA exhibited different effects on PCSK9 and LDLr.
      Altogether, these data indicate that intestinal PCSK9 is highly modulated by
      sterols and emphasize the distinct effects of BA species.

PMID- 19179625
TI  - Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small
      intestine and colon.
AB  - Actions of lubiprostone, a selective type-2 chloride channel activator, on
      mucosal secretion were investigated in guinea pig small intestine and colon. Flat
      sheet preparations were mounted in Ussing flux chambers for recording short
      circuit current (Isc) as a marker for electrogenic chloride secretion.
      Lubiprostone, applied to the small intestinal mucosa in eight concentrations
      ranging from 1-3000 nM, evoked increases in Isc in a concentration-dependent
      manner with an EC50 of 42.5 nM. Lubiprostone applied to the mucosa of the colon
      in eight concentrations ranging from 1-3000 nM evoked increases in Isc in a
      concentration-dependent manner with an EC50 of 31.7 nM. Blockade of enteric
      nerves by tetrodotoxin did not influence stimulation of Isc by lubiprostone.
      Antagonists acting at prostaglandin (PG)E2, EP1-3, or EP4 receptors did not
      suppress stimulation of Isc by lubiprostone but suppressed or abolished PGE2
      evoked responses. Substitution of gluconate for chloride abolished all responses
      to lubiprostone. The selective CFTR channel blocker, CFTR(inh)-172, did not
      suppress lubiprostone-evoked Isc. The broadly acting blocker, glibenclamide,
      suppressed (P<0.001) lubiprostone-evoked Isc. Lubiprostone, in the presence of
      tetrodotoxin, enhanced carbachol-evoked Isc. The cholinergic component, but not
      the putative vasoactive intestinal peptide component, of neural responses to
      electrical field stimulation was enhanced by lubiprostone. Application of any of
      the prostaglandins, E2, F2, or I2, evoked depolarization of the resting membrane
      potential in enteric neurons. Unlike the prostaglandins, lubiprostone did not
      alter the electrical behavior of enteric neurons. Exposure to the histamine H2
      receptor agonists increased basal Isc followed by persistent cyclical increases
      in Isc. Lubiprostone increased the peak amplitude of the dimaprit-evoked cycles.

PMID- 19179627
TI  - Small molecule inhibitors of divalent metal transporter-1.
AB  - Divalent metal transporter-1 (DMT1) is a divalent cation transporter that plays a
      key role in iron metabolism by mediating ferrous iron uptake across the small
      intestine. We have previously identified several small molecule inhibitors of
      iron uptake (4). Using a cell line that stably overexpresses DMT1, we screened
      the ability of these inhibitors to specifically block this transporter's
      activity. One compound, NSC306711, inhibited DMT1-mediated iron uptake in a
      reversible and competitive manner. This inhibitor is a polysulfonated dye
      containing two copper centers. Although one of these two sites could be chelated
      by Triethylenetetramine copper chelation did not perturb NSC306711 inhibition of
      DMT1 activity. Several other polysulfonated dyes with structural features similar
      to NSC306711 were identified as potential DMT1 transport inhibitors. This study
      characterizes important pharmacological tools that can be used to probe DMT1's
      mechanism of iron transport and its role in iron metabolism.

PMID- 19179629
TI  - HHS finalizes antiviral guidance for pandemic flu preparedness.

PMID- 19179628
TI  - Signaling pathway via TNF-alpha/NF-kappaB in intestinal epithelial cells may be
      directly involved in colitis-associated carcinogenesis.
AB  - Treatment with anti-TNF-alpha MAb has been accepted as a successful maintenance
      therapy for patients with inflammatory bowel diseases (IBD). Moreover, it has
      been recently reported that blockade of TNF receptor (TNFR) 1 signaling in
      infiltrating hematopoietic cells may prevent the development of colitis
      associated cancer (CAC). However, it remains unclear whether the TNF-alpha
      signaling in epithelial cells is involved in the development of CAC. To
      investigate this, we studied the effects of anti-TNF-alpha MAb in an animal model
      of CAC by administration of azoxymethane (AOM) followed by sequential dextran
      sodium sulfate (DSS) ingestion. We observed that the NF-kappaB pathway is
      activated in colonic epithelia from DSS-administered mice in association with
      upregulation of TNFR2 rather than TNFR1. Immunoblot analysis also revealed that
      the TNFR2 upregulation accompanied by the NF-kappaB activation is further
      complicated in CAC tissues induced in AOM/DSS-administered mice compared with the
      nontumor area. Such NF-kappaB activity in the epithelial cells is significantly
      suppressed by the treatment of MP6-XT22, an anti-TNF-alpha MAb. Despite inability
      to reduce the severity of colitis, sequential administration of MP6-XT22 reduced
      the numbers and size of tumors in association with the NF-kappaB inactivation.
      Taken together, present studies suggest that the TNFR2 signaling in intestinal
      epithelial cells may be directly involved in the development of CAC with
      persistent colitis and imply that the maintenance therapy with anti-TNF-alpha MAb
      may prevent the development of CAC in patients with long-standing IBD.

PMID- 19179630
TI  - Fospropofol approved for monitored anesthesia care.

PMID- 19179632
TI  - Consumer medication leaflets inadequate, FDA says.

PMID- 19179633
TI  - Tainted heparin crisis tested FDA's investigative skills.

PMID- 19179634
TI  - Poudre Valley wins presidential award for innovation, excellence.

PMID- 19179635
TI  - Interfaces 101: Unidirectional and bidirectional information exchange.

PMID- 19179636
TI  - Posaconazole: a new oral antifungal agent with an expanded spectrum of activity.
AB  - PURPOSE: The pharmacology, pharmacokinetics, pharmacodynamics, spectrum of
      activity and resistance, clinical utility, adverse effects, dosage and
      administration, and recommended monitoring of posaconazole are reviewed. SUMMARY:
      Posaconazole is a member of the azole class of antifungals recently approved for
      the prophylaxis and treatment of invasive fungal infections. Posaconazole has a
      large volume of distribution and distributes well into tissues. Posaconazole
      induced fungal killing is optimal when peak drug concentrations achieved are 2-10
      times the organism's minimum inhibitory concentration. Posaconazole demonstrates
      fungistatic activity against most species of Candida, Cryptococcus, and
      Trichosporon. In a direct comparison, posaconazole appeared 2-4 times more active
      than itraconazole against most pathogenic yeast species. Posaconazole also showed
      activity against Candida and Aspergillus isolates resistant to the other azoles
      and amphotericin B. Posaconazole has superior activity to the other azoles
      against Zygomycetes isolates. It has demonstrated activity equal or superior to
      other antifungal agents against almost all varieties of yeast and mold. The most
      common treatment-related adverse events associated with posaconazole are nausea,
      vomiting, diarrhea, rash, hypokalemia, thrombocytopenia, and abnormal liver
      function test values. Significant drug interactions include cimetidine,
      rifabutin, and phenytoin, for which concomitant use should be avoided, as well as
      cyclosporine, tacrolimus, and midazolam, for which dosage reductions are
      recommended. CONCLUSION: Posaconazole is an oral anti-fungal agent with a broader
      spectrum of activity and better clinical efficacy than other available
      antifungals. It is less nephrotoxic than the polyenes and probably less likely to
      be involved in drug-drug interactions than the mold-active azoles.

PMID- 19179637
TI  - Projecting future drug expenditures--2009.
AB  - PURPOSE: Drug expenditure trends in 2007 and 2008, projected drug expenditures
      for 2009, and factors likely to influence drug expenditures are discussed.
      SUMMARY: Various factors are likely to influence drug expenditures in 2009,
      including drugs in development, the diffusion of new drugs, drug safety concerns,
      generic drugs, Medicare Part D, and changes in the drug supply chain. The
      increasing availability of important generic drugs and drug safety concerns
      continue to moderate growth in drug expenditures. The drug supply chain remains
      dynamic and may influence drug expenditures, particularly in specialized
      therapeutic areas. Initial data suggest that the Medicare Part D benefit has
      influenced drug expenditures, but the ultimate impact of the benefit on drug
      expenditures remains unclear. From 2006 to 2007, total U.S. drug expenditures
      increased by 4.0%, with total spending rising from $276 billion to $287 billion.
      Drug expenditures in clinics continue to grow more rapidly than in other
      settings, with a 9.9% increase from 2006 to 2007. Hospital drug expenditures
      increased at a moderate rate of only 1.6% from 2006 to 2007; through the first
      nine months of 2008, hospital drug expenditures increased by only 2.8% compared
      with the same period in 2007. CONCLUSION: In 2009, we project a 0-2% increase in
      drug expenditures in outpatient settings, a 1-3% increase in expenditures for
      clinic-administered drugs, and a 1-3% increase in hospital drug expenditures.

PMID- 19179638
TI  - Tribute to Gloria Niemeyer Francke: Remembrances from family, friends, students,
      and colleagues.

PMID- 19179639
TI  - Praise for ASHP--A tribute to leaders.

PMID- 19179640
TI  - Preventing medication errors in hospitalized children.

PMID- 19179641
TI  - Dominant-negative loss of PPARgamma function enhances smooth muscle cell
      proliferation, migration, and vascular remodeling.
AB  - OBJECTIVE: The peroxisome proliferator activated receptor-gamma (PPARgamma)
      protein is a nuclear transcriptional activator with importance in diabetes
      management as the molecular target for the thiazolidinedione (TZD) family of
      drugs. Substantial evidence indicates that the TZD family of PPARgamma agonists
      may retard the development of atherosclerosis. However, recent clinical data have
      suggested that at least one TZD may increase the risk of myocardial infarction
      and death from cardiovascular disease. In this study, we used a genetic approach
      to disrupt PPARgamma signaling to probe the protein's role in smooth muscle cell
      (SMC) responses that are important for atherosclerosis. METHODS AND RESULTS: SMC
      isolated from transgenic mice harboring the dominate-negative P465L mutation in
      PPARgamma (PPARgamma(L/+)) exhibited greater proliferation and migration then did
      wild-type cells. Upregulation of ETS-1, but not ERK activation, correlated with
      enhanced proliferative and migratory responses PPARgamma(L/+) SMCs. After
      arterial injury, PPARgamma(L/+) mice had a approximately 4.3-fold increase in the
      development of intimal hyperplasia. CONCLUSIONS: These findings are consistent
      with a normal role for PPARgamma in inhibiting SMC migration and proliferation in
      the context of restenosis or atherosclerosis.

PMID- 19179642
TI  - Interference of progestins with endothelial actions of estrogens: a matter of
      glucocorticoid action or deprivation?

PMID- 19179644
TI  - Moderate-duration static stretch reduces active and passive plantar flexor moment
      but not Achilles tendon stiffness or active muscle length.
AB  - The effects of static stretch on muscle and tendon mechanical properties and
      muscle activation were studied in fifteen healthy human volunteers. Peak active
      and passive moment data were recorded during plantar flexion trials on an
      isokinetic dynamometer. Electromyography (EMG) monitoring of the triceps surae
      muscles, real-time motion analysis of the lower leg, and ultrasound imaging of
      the Achilles-medial gastrocnemius muscle-tendon junction were simultaneously
      conducted. Subjects performed three 60-s static stretches before being retested 2
      min and 30 min poststretch. There were three main findings in the present study.
      First, peak concentric moment was significantly reduced after stretch; 60% of the
      deficit recovered 30 min poststretch. This was accompanied by, and correlated
      with (r = 0.81; P < 0.01) reductions in peak triceps surae EMG amplitude, which
      was fully recovered at 30 min poststretch. Second, Achilles tendon length was
      significantly shorter during the concentric contraction after stretch and at 30
      min poststretch; however, no change in tendon stiffness was detected. Third,
      passive joint moment was significantly reduced after stretch, and this was
      accompanied by significant reductions in medial gastrocnemius passive muscle
      stiffness; both measures fully recovered by 30 min poststretch. These data
      indicate that the stretching protocol used in this study induced losses in
      concentric moment that were accompanied by, and related to, reductions in
      neuromuscular activity, but they were not associated with alterations in tendon
      stiffness or shorter muscle operating length. Reductions in passive moment were
      associated with reductions in muscle stiffness, whereas tendon mechanics were
      unaffected by the stretch. Importantly, the impact on mechanical properties and
      neuromuscular activity was minimal at 30 min poststretch.

PMID- 19179643
TI  - The functional importance of telomere clustering: global changes in gene
      expression result from SIR factor dispersion.
AB  - Budding yeast telomeres and cryptic mating-type loci are enriched at the nuclear
      envelope, forming foci that sequester silent information regulators (SIR
      factors), much as heterochromatic chromocenters in higher eukaryotes sequester
      HP1. Here we examine the impact of such subcompartments for regulating
      transcription genome-wide. We show that the efficiency of subtelomeric reporter
      gene repression depends not only on the strength of SIR factor recruitment by cis
      acting elements, but also on the accumulation of SIRs in such perinuclear foci.
      To monitor the effects of disrupting this subnuclear compartment, we performed
      microarray analyses under conditions that eliminate telomere anchoring, while
      preserving SIR complex integrity. We found 60 genes reproducibly misregulated.
      Among those with increased expression, 22% were within 20 kb of a telomere,
      confirming that the nuclear envelope (NE) association of telomeres helps repress
      natural subtelomeric genes. In contrast, loci that were down-regulated were
      distributed over all chromosomes. Half of this ectopic repression was SIR complex
      dependent. We conclude that released SIR factors can promiscuously repress
      transcription at nontelomeric genes despite the presence of "anti-silencing"
      mechanisms. Bioinformatic analysis revealed that promoters bearing the PAC (RNA
      Polymerase A and C promoters) or Abf1 binding consenses are consistently down
      regulated by mislocalization of SIR factors. Thus, the normal telomeric
      sequestration of SIRs both favors subtelomeric repression and prevents
      promiscuous effects at a distinct subset of promoters. This demonstrates that
      patterns of gene expression can be regulated by changing the spatial distribution
      of repetitive DNA sequences that bind repressive factors.

PMID- 19179645
TI  - Phosphodiesterase-5 inhibitors oppose hyperoxic vasoconstriction and accelerate
      seizure development in rats exposed to hyperbaric oxygen.
AB  - Oxygen is a potent cerebral vasoconstrictor, but excessive exposure to hyperbaric
      oxygen (HBO(2)) can reverse this vasoconstriction by stimulating brain nitric
      oxide (NO) production, which increases cerebral blood flow (CBF)-a predictor of
      O(2) convulsions. We tested the hypothesis that phosphodiesterase (PDE)-5
      blockers, specifically sildenafil and tadalafil, increase CBF in HBO(2) and
      accelerate seizure development. To estimate changes in cerebrovascular responses
      to hyperoxia, CBF was measured by hydrogen clearance in anesthetized rats, either
      control animals or those pretreated with one of these blockers, with the NO
      inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME), with the NO donor S
      nitroso-N-acetylpenicillamine (SNAP), or with a blocker combined with l-NAME.
      Animals were exposed to 30% O(2) at 1 atm absolute (ATA) ("air") or to 100% O(2)
      at 4 or 6 ATA. EEG spikes indicated central nervous system CNS O(2) toxicity. The
      effects of PDE-5 blockade varied as a positive function of ambient Po(2). In air,
      CBF did not increase significantly, except after pretreatment with SNAP. However,
      at 6 ATA O(2), mean values for CBF increased and values for seizure latency
      decreased, both significantly; pretreatment with l-NAME abolished these effects.
      Conscious rats treated with sildenafil before HBO(2) were also more susceptible
      to CNS O(2) toxicity, as demonstrated by significantly shortened convulsive
      latency. Decreases in regional CBF reflect net vasoconstriction in the brain
      regions studied, since mean arterial pressures remained constant or increased
      throughout. Thus PDE-5 blockers oppose the protective vasoconstriction that is
      the initial response to hyperbaric hyperoxia, decreasing the safety of HBO(2) by
      hastening onset of CNS O(2) toxicity.

PMID- 19179646
TI  - Chronic NHE-1 blockade induces an antiapoptotic effect in the hypertrophied
      heart.
AB  - Na(+)/H(+) exchanger (NHE-1) inhibition was demonstrated to induce the regression
      of cardiac hypertrophy (CH) in several experimental models and to inhibit
      mitochondrial death pathway in "in-vitro" experiments. Since recent reports show
      that NHE-1 inhibition delays the transition from CH to failure, and apoptosis
      plays a key role in this process, we investigated the effect of chronic treatment
      with the NHE-1 blocker cariporide on CH and apoptosis in the SHR. One month of
      cariporide treatment (30 mg x kg(-1) x day(-1)) induced the regression of CH
      (cardiomyocyte cross-sectional area: 468 +/- 20 vs. 285 +/- 9 microm(2) in
      untreated and cariporide-treated spontaneously hypertensive rats; P < 0.05).
      Apoptosis was assessed by TUNEL staining, the expression of Bcl-2, Bax, and
      activation of caspase-3 and PARP-1 by immunoblot. Cariporide treatment decreased
      the TUNEL-positive cells, the Bax-to-Bcl-2 ratio (3.16 +/- 0.32 vs. 1.70 +/-
      0.17, untreated and cariporide-treated, respectively; P < 0.05); caspase-3 and
      PARP-1 activation (465 +/- 62 vs. 260 +/- 22 and 2,239 +/- 62 vs. 1,683 +/- 85
      AU, untreated and cariporide-treated, respectively; P < 0.05). Angiotensin II, a
      growth factor and apoptotic stimulus, was used to induce O(2)(-) production that
      activated the ERK1/2-p90(RSK) pathway, increasing NHE-1 phosphorylation. These
      effects were prevented by losartan, N-(2-mercaptopropionyl)-glycine, and
      cariporide. In conclusion, we present data demonstrating that chronic NHE-1
      inhibition with cariporide decreases both hypertrophy and apoptosis
      susceptibility in the spontaneously hypertensive rat heart. The antiapoptotic
      effect would be the consequence of two different actions of cariporide: the
      prevention of cytosolic Na(+) and Ca(2+) overload due to the inhibition of the
      sarcolemmal NHE-1 and a direct mitochondrial effect preventing mitochondrial
      permeability transition pore opening.

PMID- 19179647
TI  - Hypoxia stimulates via separate pathways ERK phosphorylation and NF-kappaB
      activation in skeletal muscle cells in primary culture.
AB  - Mammalian cells sense oxygen levels and respond to hypoxic conditions through the
      regulation of multiple signaling pathways and transcription factors. Here, we
      investigated the effects of hypoxia on the activity of two transcriptional
      regulators, ERK1/2 and NF-kappaB, in skeletal muscle cells in primary culture. We
      found that hypoxia significantly enhanced ERK1/2 phosphorylation and that it
      stimulated NF-kappaB-dependent gene transcription as well as nuclear
      translocation of a green fluorescent protein-labeled p65 NF-kappaB isoform.
      Phosphorylation of ERK1/2- and NF-kappaB-dependent transcription by hypoxia
      required calcium entry through L-type calcium channels. Calcium release from
      ryanodine-sensitive stores was also necessary for ERK1/2 activation but not for
      NF-kappaB-dependent-transcription. N-acetylcysteine, a general scavenger of
      reactive oxygen species, blocked hypoxia-induced ROS generation but did not
      affect the stimulation of ERK1/2 phosphorylation induced by hypoxia. In contrast,
      NF-kappaB activation was significantly inhibited by N-acetylcysteine and did not
      depend on ERK1/2 stimulation, as shown by the lack of effect of the upstream ERK
      inhibitor U-0126. These separate pathways of activation of ERK1/2 and NF-kappaB
      by hypoxia may contribute to muscle adaptation in response to hypoxic conditions.

PMID- 19179648
TI  - Lipoic acid increases heat shock protein expression and inhibits stress kinase
      activation to improve insulin signaling in skeletal muscle from high-fat-fed
      rats.
AB  - The antioxidant alpha-lipoic acid (LA) has been shown to improve insulin action
      in high-fat (HF)-fed animal models, yet little is known about its underlying
      mechanisms of action. We hypothesize that LA acts by inducing heat shock proteins
      (HSPs), which then inhibit stress kinases known to interfere with insulin
      signaling intermediates. Male Wistar rats were fed a HF diet (60% calories from
      fat) for 6 wk, while controls received a chow diet (10% calories from fat). One
      half of the rats in each group received daily LA injections (30 mg/kg body wt).
      In rats fed a HF diet, LA increased expression of HSP72 and activation of HSP25
      in soleus muscle, but it had no effect on HSPs in muscle from chow-fed rats. LA
      treatment reduced phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and
      inhibitor of kappaB kinase-beta (IKKbeta) activity (IkappaBalpha protein levels)
      in rats fed a HF diet and effectively restored insulin responsiveness, as seen by
      insulin-stimulated phosphorylated Akt/Akt and 2-deoxyglucose uptake in soleus
      muscle. LA also induced activation of p38 MAPK and AMP-activated protein kinase,
      proteins previously implicated in insulin-independent glucose uptake. In
      addition, acute LA treatment induced HSPs in vitro in L6 muscle cells and
      prevented the activation of JNK and IKKbeta with stimulants such as anisomycin
      and TNF-alpha, respectively. In conclusion, our results suggest chronic LA
      treatment results in stress kinase inhibition and improved insulin signaling
      through a HSP-mediated mechanism.

PMID- 19179650
TI  - Short oxygen prebreathe periods reduce or prevent severe decompression sickness
      in a 70-kg swine saturation model.
AB  - Disabled submarine (DISSUB) survivors are expected to achieve saturation with
      inert gas. However, rescue procedures may not accommodate staged decompression,
      raising the potential for severe decompression sickness (DCS). Alternatives to
      standard recompression therapy are needed. It has been demonstrated in humans
      that isobaric oxygen "prebreathing" (OPB) can accelerate decompression in a
      DISSUB scenario. In-70 kg swine saturated at 2.82 atm absolute (ATA), 1 h of OPB
      eliminated death and reduced severe DCS. We hypothesized that even shorter
      periods (<1 h) of OPB before no-stop decompression from saturation at 2.82 ATA
      could reduce the incidence of DCS in a large animal model. Catheterized Yorkshire
      swine (68.8 +/- 1.7 kg) in individual Plexiglas boxes within a large animal
      hyperbaric chamber were compressed to 2.82 ATA for 22 h. Following saturation and
      while still at depth, breathing gas was switched to >95% O(2) for 45 min
      (OPB(45)), 15 min (OPB(15)), or 5 min (OPB(05)) of OPB, or no OPB (control). The
      chamber was then decompressed without stops (0.91 ATA/min). Observers then
      entered the chamber and recorded signs of DCS for 2 h. All OPB periods
      significantly reduced the risk of developing type II DCS. OPB(45) eliminated
      severe DCS. Controls had a 2.5 times greater risk of developing type II DCS than
      OPB(05) (P = 0.016). OPB(45) and OPB(15) significantly reduced type I DCS
      compared with controls. These results support the potential of OPB as an
      alternative to staged decompression and that OPB could be expected to improve
      outcome in a DISSUB rescue scenario.

PMID- 19179649
TI  - Sympathetic hyperactivity differentially affects skeletal muscle mass in
      developing heart failure: role of exercise training.
AB  - Sympathetic hyperactivity (SH) is a hallmark of heart failure (HF), and several
      lines of evidence suggest that SH contributes to HF-induced skeletal myopathy.
      However, little is known about the influence of SH on skeletal muscle morphology
      and metabolism in a setting of developing HF, taking into consideration muscles
      with different fiber compositions. The contribution of SH on exercise tolerance
      and skeletal muscle morphology and biochemistry was investigated in 3- and 7-mo
      old mice lacking both alpha(2A)- and alpha(2C)-adrenergic receptor subtypes
      (alpha(2A)/alpha(2C)ARKO mice) that present SH with evidence of HF by 7 mo. To
      verify whether exercise training (ET) would prevent skeletal muscle myopathy in
      advanced-stage HF, alpha(2A)/alpha(2C)ARKO mice were exercised from 5 to 7 mo of
      age. At 3 mo, alpha(2A)/alpha(2C)ARKO mice showed no signs of HF and preserved
      exercise tolerance and muscular norepinephrine with no changes in soleus
      morphology. In contrast, plantaris muscle of alpha(2A)/alpha(2C)ARKO mice
      displayed hypertrophy and fiber type shift (IIA --> IIX) paralleled by capillary
      rarefaction, increased hexokinase activity, and oxidative stress. At 7 mo,
      alpha(2A)/alpha(2C)ARKO mice displayed exercise intolerance and increased
      muscular norepinephrine, muscular atrophy, capillary rarefaction, and increased
      oxidative stress. ET reestablished alpha(2A)/alpha(2C)ARKO mouse exercise
      tolerance to 7-mo-old wild-type levels and prevented muscular atrophy and
      capillary rarefaction associated with reduced oxidative stress. Collectively,
      these data provide direct evidence that SH is a major factor contributing to
      skeletal muscle morphological changes in a setting of developing HF. ET prevented
      skeletal muscle myopathy in alpha(2A)/alpha(2C)ARKO mice, which highlights its
      importance as a therapeutic tool for HF.

PMID- 19179651
TI  - Perfluorocarbon emulsions as a promising technology: a review of tissue and
      vascular gas dynamics.
AB  - Perfluorocarbon (PFC) emulsions are halogen-substituted carbon nonpolar oils with
      resultant enhanced dissolved respiratory gas (O(2), N(2), CO(2), nitric oxide)
      capabilities. In the first demonstration of enhanced O(2) solubility, inhaled PFC
      could sustain rat metabolism. Intravenous emulsions were then trialed as "blood
      substitutes." In the last 10 yr, biocomputational modeling has enhanced our
      mechanistic understanding of PFCs. Contemporary research is now taking advantage
      of these physiological discoveries and applying PFCs as "oxygen therapeutics," as
      well as ways to enhance other gas movements. One particularly promising area of
      research is the treatment of gas embolism (arterial and venous
      emboli/decompression sickness). An expansive understanding of PFC-enhanced
      diffusive gas movements through tissue and vasculature may have analogous
      applications for O(2) or other respiratory gases and should provide a revolution
      in medicine. This review will stress the fundamental knowledge we now have
      regarding how respiratory gas movements are changed when intravenous PFC is
      present.

PMID- 19179653
TI  - Facial immersion in cold water enhances cerebral blood velocity during breath
      hold exercise in humans.
AB  - The diving response is initiated by apnea and facial immersion in cold water and
      includes, besides bradycardia, peripheral vasoconstriction, while cerebral
      perfusion may be enhanced. This study evaluated whether facial immersion in 10
      degrees C water has an independent influence on cerebral perfusion evaluated as
      the middle cerebral artery mean flow velocity (MCA V(mean)) during exercise in
      nine male subjects. At rest, a breath hold of maximum duration increased the
      arterial carbon dioxide tension (Pa(CO(2))) from 4.2 to 6.7 kPa and MCA V(mean)
      from 37 to 103 cm/s (mean; approximately 178%; P < 0.001). Similarly, during 100
      W exercise, a breath hold increased Pa(CO(2)) from 5.9 to 8.2 kPa (P < 0.001) and
      MCA V(mean) from 55 to 113 cm/s ( approximately 105%), and facial immersion
      further increased MCA V(mean) to 122 cm/s ( approximately 88%; both P < 0.001).
      MCA V(mean) also increased during 180-W exercise (from 47 to 53 cm/s), and this
      increment became larger with facial immersion (76 cm/s, approximately 62%; P <
      0.001), although Pa(CO(2)) did not significantly change. These results indicate
      that a breath hold diverts blood toward the brain with a >100% increase in MCA
      V(mean), largely because Pa(CO(2)) increases, but the increase in MCA V(mean)
      becomes larger when combined with facial immersion in cold water independent of
      Pa(CO(2)).

PMID- 19179652
TI  - Right coronary artery becomes stiffer with increase in elastin and collagen in
      right ventricular hypertrophy.
AB  - Changes in blood flow influence the structure, function, mechanical properties,
      and remodeling of arteries. The objective of the present study was to investigate
      the role of increased blood flow on the biaxial incremental elastic moduli of the
      porcine right coronary artery (RCA) and to determine the microstructural basis
      for the changes in moduli. We hypothesized that an increase in RCA flow will lead
      to increased stiffness in conjunction with remodeling of elastin and collagen in
      the vessel wall. The control and experimental groups consisted of five RCA
      vessels each. The RCA of the experimental group was exposed to 4 wk of flow
      overload in right ventricular hypertrophy induced by pulmonary artery banding.
      Stress-strain relationships were determined and the incremental elastic moduli
      were derived in the circumferential, axial, and cross directions. The results
      show a significant increase in the elastic moduli in the circumferential (262.7
      +/- 15.7 vs. 120.2 +/- 12.4 kPa; P < 0.001), axial (177.8 +/- 25.5 vs. 100.3 +/-
      11.9 kPa; P = 0.025), and cross directions (104.8 +/- 8.2 vs. 68.2 +/- 8.6 kPa; P
      = 0.016) of the experimental RCA compared with controls. Multiphoton microscopy
      was used to assess the changes in elastin and collagen content in the media and
      adventitia of the vessel wall. We found a significant increase in elastin and
      collagen area fraction particularly in the adventitial layer. These data suggest
      stiffening of the vessel wall as a result of increased elastin and more
      predominantly collagen.

PMID- 19179654
TI  - The balancing act between the cellular processes of protein synthesis and
      breakdown: exercise as a model to understand the molecular mechanisms regulating
      muscle mass.

PMID- 19179655
TI  - A history of recurrent positive selection at the toll-like receptor 5 in
      primates.
AB  - Many genes involved in immunity evolve rapidly. It remains unclear, however, to
      what extent pattern-recognition receptors (PRRs) of the innate immune system in
      vertebrates are subject to recurrent positive selection imposed by pathogens, as
      suggested by studies in Drosophila, or whether they are evolutionarily
      constrained. Here, we show that Toll-like receptor 5 (TLR5), a member of the Toll
      like receptor family of innate immunity genes that responds to bacterial
      flagellin, has undergone a history of adaptive evolution in primates. We have
      identified specific residues that have changed multiple times, sometimes in
      parallel in primates, and are thus likely candidates for selection. Most of these
      changes map to the extracellular leucine-rich repeats involved in pathogen
      recognition, and some are likely to have an effect on protein function due to the
      radical nature of the amino acid substitutions that are involved. These findings
      suggest that vertebrate PRRs might show similar patterns of evolution to
      Drosophila PRRs, in spite of the acquisition of the more complex and specific
      vertebrate adaptive immune system. At shorter timescales, however, we found no
      evidence of adaptive evolution in either humans or chimpanzees. In fact, we found
      that one mutation that abolishes TLR5 function is present at high frequencies in
      many human populations. Patterns of variation indicate that this mutation is not
      young, and its high frequency suggests some functional redundancy for this PRR in
      humans.

PMID- 19179656
TI  - Both sides now: multiple interactions of ATP with pannexin-1 hemichannels. Focus
      on "A permeant regulating its permeation pore: inhibition of pannexin 1 channels
      by ATP".

PMID- 19179657
TI  - Hypophosphorylation of the Stiff N2B titin isoform raises cardiomyocyte resting
      tension in failing human myocardium.
AB  - High diastolic stiffness of failing myocardium results from interstitial fibrosis
      and elevated resting tension (F(passive)) of cardiomyocytes. A shift in titin
      isoform expression from N2BA to N2B isoform, lower overall phosphorylation of
      titin, and a shift in titin phosphorylation from N2B to N2BA isoform can raise
      F(passive) of cardiomyocytes. In left ventricular biopsies of heart failure (HF)
      patients, aortic stenosis (AS) patients, and controls (CON), we therefore related
      F(passive) of isolated cardiomyocytes to expression of titin isoforms and to
      phosphorylation of titin and titin isoforms. Biopsies were procured by
      transvascular technique (44 HF, 3 CON), perioperatively (25 AS, 4 CON), or from
      explanted hearts (4 HF, 8 CON). None had coronary artery disease. Isolated,
      permeabilized cardiomyocytes were stretched to 2.2-microm sarcomere length to
      measure F(passive). Expression and phosphorylation of titin isoforms were
      analyzed using gel electrophoresis with ProQ Diamond and SYPRO Ruby stains and
      reported as ratio of titin (N2BA/N2B) or of phosphorylated titin (P-N2BA/P-N2B)
      isoforms. F(passive) was higher in HF (6.1+/-0.4 kN/m(2)) than in CON (2.3+/-0.3
      kN/m(2); P<0.01) or in AS (2.2+/-0.2 kN/m(2); P<0.001). Titin isoform expression
      differed between HF (N2BA/N2B=0.73+/-0.06) and CON (N2BA/N2B=0.39+/-0.05;
      P<0.001) and was comparable in HF and AS (N2BA/N2B=0.59+/-0.06). Overall titin
      phosphorylation was also comparable in HF and AS, but relative phosphorylation of
      the stiff N2B titin isoform was significantly lower in HF (P-N2BA/P-N2B=0.77+/
      0.05) than in AS (P-N2BA/P-N2B=0.54+/-0.05; P<0.01). Relative hypophosphorylation
      of the stiff N2B titin isoform is a novel mechanism responsible for raised
      F(passive) of human HF cardiomyocytes.

PMID- 19179658
TI  - Plasma-advanced oxidation protein products are potent high-density lipoprotein
      receptor antagonists in vivo.
AB  - Advanced oxidation protein products (AOPPs) are carried by oxidized plasma
      proteins, especially albumin and accumulate in subjects with renal disease and
      coronary artery disease. AOPPs represent an excellent novel marker of oxidative
      stress and their roles in the development of cardiovascular disease might be of
      great importance. Here, we show that in vitro-generated AOPP-albumin binds with
      high affinity to the high-density lipoprotein (HDL) receptor scavenger receptor
      class B type I (SR-BI). Already an equimolar concentration of AOPP-albumin to HDL
      blocked HDL association to SR-BI and effectively inhibited SR-BI-mediated
      cholesterol ester (CE) uptake. Interestingly, albumin extensively modified by
      advanced glycation end products (AGE-albumin), which is an established SR-BI
      ligand known to accumulate in renal disease, only weakly interfered with HDL
      binding to SR-BI. Furthermore, AOPP-albumin administration increased the plasma
      half-life of [3H]CE-HDL in control mice 1.6-fold (P=0.01) and 8-fold (P=0.0003)
      in mice infected with adenoviral vectors encoding human SR-BI. Moreover, albumin
      isolated from hemodialysis patients, but not albumin isolated from healthy
      controls, markedly inhibited SR-BI-mediated HDL-CE transfer in vitro dependent on
      the AOPP content of albumin. These results indicate that AOPP-albumin effectively
      blocks SR-BI in vitro and in vivo. Thus, depressed plasma clearance of HDL
      cholesterol may contribute to the abnormal composition of HDL and the high
      cardiovascular risk observed in patients with chronic renal failure.

PMID- 19179659
TI  - Regulatory role of G protein-coupled estrogen receptor for vascular function and
      obesity.
AB  - We found that the selective stimulation of the intracellular, transmembrane G
      protein-coupled estrogen receptor (GPER), also known as GPR30, acutely lowers
      blood pressure after infusion in normotensive rats and dilates both rodent and
      human arterial blood vessels. Stimulation of GPER blocks vasoconstrictor-induced
      changes in intracellular calcium concentrations and vascular tone, as well as
      serum-stimulated cell proliferation of human vascular smooth muscle cells.
      Deletion of the GPER gene in mice abrogates vascular effects of GPER activation
      and is associated with visceral obesity. These findings suggest novel roles for
      GPER in protecting from cardiovascular disease and obesity.

PMID- 19179660
TI  - Calcium, calpains, and cardiac hypertrophy: a new link.

PMID- 19179662
TI  - Harmony and discord in endothelial calcium entry.

PMID- 19179663
TI  - Sex hormones save our skin: the vascular networking of estrogen.

PMID- 19179661
TI  - Branching morphogenesis.

PMID- 19179664
TI  - Searching for miR-acles in cardiac fibrosis.

PMID- 19179665
TI  - Cyclooxygenase-2-derived prostaglandin F2alpha: an endothelium-derived
      contractile factor acting independently of other endothelium-derived contractile
      factors via vascular thromboxane receptors.

PMID- 19179666
TI  - The cornucopia of "pleiotropic" actions of statins: myogenesis as a new mechanism
      for statin-induced benefits?

PMID- 19179667
TI  - NADPH oxidase in vascular injury: a new insight about its regulation and role in
      T cells.

PMID- 19179668
TI  - Autophagy in ischemic heart disease.
AB  - Autophagy is a major catabolic pathway by which mammalian cells degrade and
      recycle macromolecules and organelles. It plays a critical role in removing
      protein aggregates, as well as damaged or excess organelles, to maintain
      intracellular homeostasis and to keep the cell healthy. In the heart, autophagy
      occurs at low levels under normal conditions, and defects in this process cause
      cardiac dysfunction and heart failure. However, this pathway is rapidly
      upregulated under environmental stress conditions, including ATP depletion,
      reactive oxygen species, and mitochondrial permeability transition pore opening.
      Although autophagy is enhanced in various pathophysiological conditions, such as
      during ischemia and reperfusion, the functional role of increased autophagy is
      not clear and is currently under intense investigation. In this review, we
      discuss the evidence for autophagy in the heart in response to ischemia and
      reperfusion, identify factors that regulate autophagy, and analyze the potential
      roles autophagy might play in cardiac cells.

PMID- 19179670
TI  - Inter-rater reliability of the DRS-R-98 in detecting delirium in frail elderly
      patients.

PMID- 19179669
TI  - Shared circuitry: developmental signaling cascades regulate both embryonic and
      adult coronary vasculature.
AB  - Ischemic heart disease is the most common cause of heart failure and is among the
      leading causes of mortality worldwide. Therapies used for the treatment of this
      disease aim to restore blood flow to severely narrowed or occluded coronary
      arteries by either catheter-based or surgical means. Although these strategies
      prove efficacious for many patients, a substantial number of individuals fail to
      improve following these procedures. Recently, a noninvasive strategy has been
      proposed, focusing on the use of endogenous growth factors that trigger the
      growth of new coronary arteries. Using the developing heart as a model, several
      groups have identified some of the key pathways that not only govern the
      development of the coronary vascular system but also promote the growth of the
      adult coronary vasculature. Here, we review the major morphological events and
      signaling cascades that mediate the formation of the coronary vasculature in the
      embryo. We further describe the mechanism by which many of these same pathways
      also regulate the adult coronary vasculature and their potential use in the
      treatment of ischemic heart disease.

PMID- 19179671
TI  - World Diabetes Day 2008: focusing on the children!

PMID- 19179672
TI  - Introducing the movement for global mental health.

PMID- 19179673
TI  - Global warming & heatstroke.

PMID- 19179674
TI  - The Inter-Governmental Working Group on Public Health, Innovation and
      Intellectual Property (IGWG)--the way ahead.

PMID- 19179675
TI  - Can maternal leptin level at early gestation be used as a predictor of postpartum
      weight retention?

PMID- 19179676
TI  - IDD as a public health problem.

PMID- 19179677
TI  - Microbes in the gut: a digestable account of host-symbiont interactions.
AB  - The human bowel is host to a diverse group of bacteria with over 500 different
      bacterial species contributing to this diversity. Until recently these bacteria
      were regarded as residents without any specific functions. The last two decades
      have seen a radical change in our understanding of the interactions between the
      gut flora and their eukaryotic hosts and there is a growing appreciation of the
      spectrum of functions performed by these symbionts. Intestinal bacteria are
      recognized for their role in nutrient absorption, mucosal barrier function,
      angiogenesis, morphogenesis and postnatal maturation of intestinal cell lineages,
      intestinal motility and more importantly maturation of gut associated lymphoid
      tissue (GALT). Although gut flora are implicated in certain pathological
      disorders, their remarkable contributions to health and homeostasis of the host
      need to be recognized and understood.

PMID- 19179678
TI  - Evaluation of plasma leptin levels & BMI as predictor of postpartum weight
      retention.
AB  - BACKGROUND & OBJECTIVE: Plasma leptin level during pregnancy has been reported as
      a biochemical predictor of postpartum weight retention. The objective of this
      study was to determine the relationship between pregnancy-related factors
      including plasma leptin and postpartum weight retention in Korean women. METHODS:
      A convenience sampling method was used among women attending a high-risk
      pregnancy clinic in Pusan National University Hospital, Busan, between March 2002
      and February 2003. We investigated 75 women during pregnancy and 6 months
      postpartum. Plasma leptin levels were measured using an ELISA. The weight gain
      during pregnancy and postpartum weight retention, and the correlation between the
      plasma leptin levels and body weight were evaluated. RESULTS: The plasma leptin
      levels at the 1(st) trimester and body weight at 24 wk of gestation, 6 wk, and 6
      months postpartum differed significantly between the underweight and overweight
      groups and between the normal and overweight groups. Plasma leptin levels during
      the first trimester correlated with the initial BMI at first visit and term, and
      body weight at term, while the initial BMI significantly correlated with the body
      weight at term, 6 months postpartum, and 6 months postpartum. INTERPRETATION &
      CONCLUSION: Our findings suggest that the plasma leptin level in the first
      trimester is a predictor of maternal weight at term, while initial BMI is a
      better predictor of maternal weight at 6 wk and 6 months postpartum. Further,
      postpartum weight retention was more dependent on first pre-natal visit factors
      rather than weight changes during pregnancy. Anthropometric measures at first pre
      natal visit to prevent postpartum obesity can be recommended.

PMID- 19179679
TI  - Dietary supplies of iodine & thiocyanate in the aetiology of endemic goitre in
      Imphal East district of Manipur, north east India.
AB  - BACKGROUND & OBJECTIVE: The present investigation was undertaken to study the
      iodine nutritional status of school children of Imphal east district in Manipur
      where endemic goitre persists during post-salt iodization phase along with the
      investigation of the factors responsible for the occurrence of goitre endemicity.
      METHODS: A total of 1,286 children (6-12 yr) were clinically examined for goitre
      from study areas of Imphal east district. A total of 160 urine samples were
      collected and analyzed to measure urinary iodine and thiocyanate levels. Iodine
      content was measured in 140 salt samples and 16 drinking water samples. RESULTS:
      Overall goitre prevalence was about 30 per cent (grade 1-24.7%; grade 2-5.3%) and
      median urinary iodine level was 17.25 microg/dl. The mean urinary thiocyanate
      level was 1.073 +/- 0.39 mg/dl. Iodine/thiocyanate ratio (microg/mg) was in the
      ranges from 15.65 to 22.34. The mean iodine content in drinking water samples was
      2.92 +/- 1.75 microg/l and 97.8 per cent of edible salts had iodine level above
      15 ppm at the consumption point. INTERPRETATION & CONCLUSION: Our findings showed
      that in spite of no biochemical iodine deficiency, iodine deficiency disorders
      (IDD) is a serious public health problem in Imphal east district of Manipur. The
      consumption pattern of certain plant foods containing thiocyanate (or its
      precursors) was relatively high that interfere with thyroid hormone synthesis
      resulting in the excretion of more iodine. Thus, the existing dietary supplies of
      thiocyanate in relation to iodine may be a possible aetiological factor for the
      persistence of endemic goitre in the study region during post salt iodization
      period.

PMID- 19179680
TI  - Human sperm centrin levels & outcome of intracytoplasmic sperm injection (ICSI)-
      a pilot study.
AB  - BACKGROUND & OBJECTIVE: The objective of the present study was to compare the
      levels of sperm centrin a centrosomal protein that influences cell migration, in
      normal fertile donors and in oligoasthenozoospermic males (count 5 million/ml and
      motility <40%, grade c+d) undergoing intracytoplasmic sperm injection (ICSI) and
      to correlate with the outcome of ICSI. METHODS: The prospective study carried out
      at Inkus IVF Centre, Mumbai, India, during (January-December 2003). It included
      20 normal fertile donor males (group I) and 20 oligoasthnozoospermic (OA) males
      (group II). Group II was further divided in II a and II b according to the
      centrin levels. Centrin levels were measured by using enzyme linked immunosorbent
      assay (ELISA) in both groups. All participants underwent an ICSI procedure and
      the levels of centrin and outcome of ICSI were correlated. RESULTS: Centrin
      levels were significantly lower (P<0.001) in group II (0.39) as compared with
      group I (1.34). With centrin levels <0.45 optical density (OD) (group II a) the
      pregnancy rate was further reduced, with only 2 pregnancies (out of 14) both of
      which, ended in abortion. Cases in group II showed levels of centrin much lower
      than in the fertile group. Further lowered centrin levels were associated with
      lowered pregnancy rates in OA males, but statistically was not significant.
      INTERPRETATION & CONCLUSION: The study revealed that lower centrin levels in OA
      males resulted in lower pregnancy percentage in this group after ICSI.
      Disturbances in centrosomal protein could be one of the possible causes of ICSI
      failure.

PMID- 19179681
TI  - Pharmacokinetics of pyrazinamide in children with primary progressive disease of
      lungs.
AB  - BACKGROUND & OBJECTIVE: As the dosages recommended for children are based on
      weight, empirical and derived by extrapolation from the studies in adults,
      pyrazinamide (PZA) pharmacokinetics in children is likely to be different from
      adults. Limited information exists regarding the pharmacokinetics of PZA in
      paediatric patients of primary progressive disease (PPD) of lungs. This study
      aims to look at the changed pharmacokinetics of pyrazinamide in children with PPD
      of lungs by using reverse phase high-pressure liquid chromatography (HPLC).
      METHODS: A total of 40 children (age range 5 to 13 yr) of PPD were receiving
      pyrazinamide (30 mg/kg/day). On 11(th) day of short course antitubercular
      therapy, blood samples (two per day from 11(th) to 13(th) day) were collected at
      0 h (pre-dose), 1, 2, 3, 4, 8 and 24 h after pyrazinamide administration and
      concentration of pyrazinamide was estimated by reverse phase high-pressure liquid
      chromatography. The mean peak serum concentration, the time to reach mean peak
      serum concentration, total clearance, concentration at time zero, volume of
      distribution, terminal elimination rate constant, elimination half-life, total
      area under serum concentration-time curve were measured. RESULTS: The mean serum
      concentrations of pyrazinamide were found higher than its minimum inhibitory
      concentration (20 microg/ml) required to inhibit the growth of tubercle bacilli
      from 1 to 8 h continuously. INTERPRETATION & CONCLUSION: Our results suggest that
      a dose of 30 mg/kg/day achieves much higher concentration of pyrazinamide as
      compared to its minimum inhibitory concentration (20 microg/ml). Therefore,
      lowering of pyrazinamide dosage is suggested in children for better patient
      compliance along with reduction in cost, side-effects and toxicity without
      compromising its efficacy.

PMID- 19179682
TI  - Influence of feeder layer on the expression of stem cell markers in cultured
      limbal corneal epithelial cells.
AB  - BACKGROUND & OBJECTIVE: The limbus is enriched with the stem cells of corneal
      epithelium. Auto- and allograft limbal transplantations are effective in
      restoring the corneal epithelium and inhibiting inflammation and
      neovascularization. Preserved human amniotic membrane (AM) is now widely used as
      a substrate for ocular surface reconstruction. The combination of limbal and AM
      transplantation has been shown to improve the surgical outcome in patients with
      total limbal stem cell deficiency (LSCD). The purpose of this study was to
      compare the expression of putative stem cell markers ATP binding cassette protein
      (ABCG2) and keratinocyte stem cell marker: p63 and differentiation markers.
      (connexin 43 and keratin 3 / keratin 12) on the limbal epithelial cells cultured
      over the denuded AM with and without the 3T3 murine fibroblast cells as feeder
      layer. METHODS: Human limbal tissues obtained from the cadaveric donor eyes were
      cultured over the denuded human amniotic membrane in the presence of mitomycin C
      treated 3T3 fibroblasts and the cultured cells studied for the expression of
      ABCG2 and p63 by immunohistochemistry and Western blot. Semi-quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) was done on the cultured cells
      at varying intervals of time for expression of ABCG2, p63, connexin43 (Cnx43),
      and keratin 3 (K3) and keratin 12 (K12). RESULTS: The growth rates were similar
      in both denuded AM and denuded AM + 3T3. The cells cultured over AM + 3T3 showed
      the expression of p63 and ABCG2 till 21 days of incubation by
      immunohistochemistry and Western blot. The expression of p63 and ABCG2 were
      retained till 21 days of incubation on the cells cultured over denuded AM + 3T3,
      whereas it was expressed only till day 8 on the cells cultured over the denuded
      membrane by semi quantitative RT-PCR. Cnx43 and K3/K12 were observed in both the
      conditions. INTERPRETATION & CONCLUSION: The limbal epithelial cells cultured in
      the presence of mitomycin C treated 3T3 feeder layer were able to maintain the
      expression of putative stem cell markers. Further in vitro studies using feeder
      layer will enable us to understand the factors, which play a role in maintaining
      the limbal stem cell niche.

PMID- 19179683
TI  - Community practices of using bed nets & acceptance & prospects of scaling up
      insecticide treated nets in north-east India.
AB  - BACKGROUND & OBJECTIVE: The National Vector Borne Disease Control Programme
      (NVBDCP), India has been promoting and scaling up the use of insecticide-treated
      nets (ITNs) in the tribal dominated malarious areas of north-east India. But,
      information on sleeping habits, bed net ownership and use practices, and feedback
      of communities in ITN--targeted areas is needed for formulating a strategic
      framework for upscaling the coverage of ITNs. We carried out a community-based
      cross-sectional survey in select areas of Nagaland and Mizoram (where ITNs were
      introduced) along with Assam (where ITNs were not introduced) to know the
      response of community. METHODS: Following large scale introduction of ITNs during
      2001-2002 in the north-eastern States of Nagaland and Mizoram by NVBDCP, India, a
      cross-sectional community-based survey was undertaken in April-May, 2003 covering
      435 households of Nagaland and 464 households in Mizoram, using a structured
      questionnaire, to assess the demographic variables relevant to bed net use, bed
      net washing practices and acceptability of ITNs etc., for upscaling the coverage
      of ITNs in the surveyed communities. A total of 448 households in 8 villages in a
      non-ITN PHC area of Assam were served as the control area. RESULTS: The average
      bet net usage per family (2.01 to 2.65). Bed net use was mostly seasonal in
      Nagaland where a majority (65.1-78.7%) used bed nets only during summers and
      monsoon as compared to the year round use in Mizoram (83.5%) and Assam (78.9%).
      Frequent washing of nets was most common in Assamese communities with 77 per cent
      households washing their nets at least once in a month. More than two third users
      favoured use of ITNs over the conventional indoor residual spray of DDT for
      malaria control. INTERPRETATION & CONCLUSION: ITNs are widely acceptable in the
      user communities and a demand for ITNs is evident in the non-user communities of
      north-east India. Approach of treating community owned nets through an efficient
      service delivery mechanism will be a viable option for upscaling the ITN
      coverage.

PMID- 19179684
TI  - Utility of the rDNA-ITS2-PCR assay in detecting the life stages of species S of
      Anopheles fluviatilis complex.
AB  - BACKGROUND & OBJECTIVE: Anopheles fluviatilis, which ranks second among the major
      malarial vectors in India occurs as a complex of three morphologically identical
      species (species S, T and U) of which only species S is a vector. Hence, it
      becomes pertinent to have a method for the detection of this vector species under
      field conditions to map the distribution of this vector. An rDNA-ITS2-PCR assay
      has been developed earlier for species S of this complex using female adult
      specimens. In order to widen the range of samples on which this technique can be
      employed, the utility of this PCR assay in detecting different life
      stages/gender/parts of the vector species was studied. Also, its reliability in
      detecting a single species S in pools of species T was studied. METHODS:
      Mosquitoes were collected from Malkangiri and Koraput districts of Orissa State
      where species S and T of this complex are reported. The wild caught fed females,
      after egg laying were subjected to PCR assay for species identification. The F1
      progeny of a few PCR identified specimens was raised and samples at larval, pupal
      and adult stages were used for PCR assay. Single adult specimen of species S was
      added to pools containing different numbers of adults of species T and the pools
      were subjected to DNA extraction and PCR assay. RESULTS: The PCR assay could
      detect species S from pure DNA extracts of the immature stages and crude DNA
      extracts of parts of adult/whole adult mosquito of either gender. Crude DNA
      extracts of pools of mosquitoes had to be diluted and used in order to obtain the
      species diagnostic fragment. INTERPRETATION & CONCLUSION: The rDNA-ITS2-PCR assay
      producing an amplicon of 350 bp. diagnostic for species S, could detect all
      stages/gender. Any part of the adult can be used for species identification.
      Further, a single adult of species S in pools of as many as 99 adults of species
      T could be detected. Application of this PCR assay will be useful in mapping the
      distribution of species S, an important malarial vector.

PMID- 19179685
TI  - Novel mutations in emb B gene of ethambutol resistant isolates of Mycobacterium
      tuberculosis: a preliminary report.
AB  - BACKGROUND & OBJECTIVE: Ethambutol (EMB) resistance, thought to be occurring due
      to mutations in embB gene of Mycobacterium tuberculosis on the rise is a cause of
      grave concern. The present study was planned to investigate the presence of EMB
      resistance in M. tuberculosis isolates and to look for prevalent mutations in
      embB gene. METHODS: A total of 591(283 from new and 308 from previously treated
      cases) sputum samples from the same number of pulmonary tuberculosis cases were
      cultured. Isolates were tested by 1 per cent proportion method for resistance to
      isoniazid, rifampicin streptomycin and ethambutol. Minimum inhibitory
      concentration (MIC) of EMB was measured by absolute concentration method. Ten
      randomly selected isolates were subjected to single strand conformational
      polymorphism (SSCP) and direct DNA sequencing to look for mutation in 364 bp
      segments of embB gene. RESULTS: Of 353 isolates of M. tuberculosis from 591
      sputum samples, 62 (17.58%) were resistant to EMB, of which, 16 (25.8%) showed
      initial resistance and 46 (74.2%) acquired. Mono resistance to EMB was rare. Only
      two isolates showed resistance to EMB alone. From 62 EMB resistant isolates, 88.7
      per cent (55) were resistant to INH, 82.2 per cent (51) to rifampicin and 61.2
      per cent (38) were resistant to streptomycin. Co-resistance to isoniazid and
      rifampicin (multidrug resistant, MDR-TB) with EMB resistance was seen in
      41(66.1%) isolates. High level of EMB resistance was seen in 16.5 per cent
      isolates. SSCP showed altered mobility in 8 of 10 isolates tested. Among the 8
      mutants, 4 had known mutations at codon Met 306 being replaced by Val/ Leu. The
      second most frequent mutation encountered was at codon Phe 287 being replaced by
      Val, Cys or Leu (novel mutations). Sequence analysis revealed 10 novel mutations
      in codon 221, 225, 227, 271, 272, 281, 282, 287, 293 and 294 within embB gene.
      INTERPRETATION & CONCLUSION: Presence of high frequency of EMB resistance,
      occurrence of high level EMB resistance, co-existence of MDR-TB with EMB
      resistance and novel mutations in emb B gene of M. tuberculosis clinical isolates
      reported highlight the need to work on larger samples to identify the diagnostic
      marker of EMB resistance in mycobacteria.

PMID- 19179686
TI  - Risk of hepatitis C infection among injection drug users in Mizoram, India.
AB  - BACKGROUND & OBJECTIVE: Prevalence of injection drug users (IDUs) is high in the
      northeastern region of India. This coupled with unsafe injecting practices as
      well as practice of tattooing in remote tribal areas call for baseline data on
      the prevalence of parentally transmitted viral diseases. In the present study we
      aimed to measure the risk behaviours and seroprevalence of hepatitis C virus
      (HCV) antibodies amongst IDUs of Mizoram, a State of the northeast India.
      METHODS: A cross-sectional study was conducted in 2004-2005 amongst IDUs
      (including female sex workers) who had injected in the past six months and were
      unaware of their HCV/HIV status. They were recruited from various drop-in centers
      from Aizawl, Mizoram, and screened for anti-HCV antibodies using 3(rd) generation
      HCV EIA and recombinant immunoblot assay (RIBA). RESULTS: The prevalence of HCV
      antibodies was 71.2 per cent among the active IDUs. On univariate analysis
      increasing duration of injection, syringe sharing and heroin (diacetylmorphine)
      injectors were at a significantly higher risk of acquiring HCV antibodies
      (P<0.001). On multivariate analysis, HCV antibody prevalence showed a strong
      association with the type of drugs injected (P=0.001), frequency of injecting
      (P=0.013), multiplicity of drugs abused (P=0.004), and needle syringe sharing
      (P=0.003). INTERPRETATION & CONCLUSION: Unsafe injecting practices were found to
      be associated with a higher risk of acquiring hepatitis C infection. Our findings
      showed that syringe and needle exchange programme alone was not sufficient as a
      preventive strategy for control of hepatitis C infection among IDUs of Aizawl.

PMID- 19179687
TI  - Effect of Hemidesmus indicus R.Br. root extract against Salmonella enterica
      serovar Typhimurium-induced apoptosis in murine macrophage cell line (P388D1).
AB  - BACKGROUND & OBJECTIVE: Previous studies on natural products had mainly dealt
      with their antimicrobial activity and studies on the interference of these
      bioactive compounds with host-bacterial interaction is limited. The present study
      was undertaken to investigate the effect of the sterols and fatty acids present
      in the chloroform fraction of crude methanol extract of Hemidesmus indicus root
      (CHI) on Salmonella enterica serovar Typhimurium (S. Typhimurium) mediated
      apoptosis in a murine macrophage cell line (P388D1). METHODS: Bacterial
      sensitivity test was carried out with different concentrations of CHI and the
      optimum dose was fixed as 100 mug/ml for CHI, which was safe on host cells as the
      CD(50) (50% of cell death) dose of CHI was determined to be 500 mug/ml in the
      P388D1 cell line. RESULTS: The CHI-treated bacteria had negligible cytotoxicity
      and were less potent to invade and proliferate intracellularly. Murine
      macrophages infected with wild bacteria, stained with Hoechst 33258, had swollen
      and damaged morphology with characteristic apoptotic bodies whereas macrophages
      infected with treated bacteria had comparative normal architecture.
      Immunofluorescence and transmission electron micrographs both confirmed that CHI
      treated bacteria were defective and smaller than the wild bacteria.
      Ultrastructures of P388D1 cells infected with wild bacteria showed many ingested
      bacteria and characteristic Salmonella-containing vacuoles (SCV). Some cells had
      condensed or fragmented nuclei with swollen mitochondria, whereas most of the
      cells infected with treated bacteria were normal in morphology and a few had
      internalized bacteria, but the typical bacteria laden SCV was not observed in
      cells infected with CHI-treated S. Typhimurium. INTERPRETATION & CONCLUSION: Our
      results showed that the choloroform fraction of H. indicus root blocked the
      cytotoxic activity of S. Typhimurium in a macrophage cell line. More studies need
      to be done to elaborate and confirm our findings.

PMID- 19179688
TI  - Detection of Chlamydophila pneumoniae (Chlamydia pneumoniae) in endarteroctomy
      specimens of coronary heart diseases patients.
AB  - BACKGROUND & OBJECTIVE: Association of Chlamydia pneumoniae with atherosclerosis
      and coronary artery disease is debated. Increased antibody levels against C.
      pneumoniae in patients with coronary artery disease is widely reported. Direct
      evidence would be demonstration of C. pneumoniae, its antigen or genome in the
      diseased arterial tissue. This study was thus conducted to look for antigen or
      genome of C. pneumoniae in coronary artery specimens from patients with coronary
      artery disease along with serology. METHODS: Sixty two end arteriotomy specimens
      of discarded coronary arteries from patients of coronary heart disease were
      tested for presence of C.pnuemoniae genome using 2 nested PCR assays and antigen
      detection by immuno-fluorescence assay. Presence of species specific antibodies
      were also tested in the patients. RESULTS: C. pneumoniae could not be detected by
      PCR or immunofluorescence assay in any specimen. C. pnuemoniae Ig G antibody was
      detected in 42 of the 62 (67.7%) patients studied, compared to 10 of the 23
      (43.47%) of controls. Moreover 18 of 62 (29%) patients compared to 4 of 23
      (17.39%) controls possessed IgA antibodies. INTERPRETATION & CONCLUSION:
      Association of C.pneumoniae and coronary artery disease would not be established
      by genome or antigen detection. However, C. pneumoniae antibodies were detected
      in more number of patients than controls. More studies are required to reach to a
      conclusion.

PMID- 19179689
TI  - The influence of glucose added urine on the in vitro antimicrobial activity of
      various antibiotics.
AB  - BACKGROUND & OBJECTIVE: Factors associated with the medium, including calcium and
      magnesium ion concentration and pH have been shown to affect the results of
      susceptibility testing but very little is known about glycosuria and the effect
      of glucose on the antimicrobial effect of antibiotics. In this study we assessed
      the influence of glucose added urine on the in vitro activities of various
      antibiotics by the microbroth dilution method. METHODS: Sixteen Escherichia coli
      isolates from patients with urinary infections were used in this study. Nine
      antibiotics were tested for their antimicrobial activity. Minimum inhibitory
      concentrations (MICs) were performed by the microbroth dilution method parallel
      in Mueller Hinton broth and glucose added urine. RESULTS: MICs of nearly all
      antibiotics were higher in glucose added urine than MICs in broth. MIC(90)
      against ampicillin was 32-fold higher in glucose added urine than MIC(90) in
      broth. MIC(90)s against ampicillin-sulbactam, cephalothin, cefuroxime,
      ceftriaxone and ciprofloxacin in glucose added urine were significantly (P<0.05)
      higher than MIC(90) in broth. Equal MIC(90) in glucose added urine and broth were
      obtained for amikacin, sulphamethoxazole and trimethoprime. INTERPRETATION &
      CONCLUSION: Our findings demonstrated that MICs of antibiotics are influenced by
      the glucose added urine.

PMID- 19179690
TI  - Down syndrome like appearance with a novel de novo translocation
      t(6;21)(q21;q13).

PMID- 19179691
TI  - Resurgence of diphtheria in India in the 21st century.

PMID- 19179692
TI  - Use of two double disk synergy tests to detect metallo beta lactamases in
      nonfermenters.

PMID- 19179693
TI  - Dietary calcium deficiency & rickets.

PMID- 19179695
TI  - Barking up the wrong treelength: the impact of gap penalty on alignment and tree
      accuracy.
AB  - Several methods have been developed for simultaneous estimation of alignment and
      tree, of which POY is the most popular. In a 2007 paper published in Systematic
      Biology, Ogden and Rosenberg reported on a simulation study in which they
      compared POY to estimating the alignment using ClustalW and then analyzing the
      resultant alignment using maximum parsimony. They found that ClustalW+MP
      outperformed POY with respect to alignment and phylogenetic tree accuracy, and
      they concluded that simultaneous estimation techniques are not competitive with
      two-phase techniques. Our paper presents a simulation study in which we focus on
      the NP-hard optimization problem that POY addresses: minimizing treelength. Our
      study considers the impact of the gap penalty and suggests that the poor
      performance observed for POY by Ogden and Rosenberg is due to the simple gap
      penalties they used to score alignment/tree pairs. Our study suggests that
      optimizing under an affine gap penalty might produce alignments that are better
      than ClustalW alignments, and competitive with those produced by the best current
      alignment methods. We also show that optimizing under this affine gap penalty
      produces trees whose topological accuracy is better than ClustalW+MP, and
      competitive with the current best two-phase methods.

PMID- 19179696
TI  - Budgeted phylogenetic diversity on circular split systems.
AB  - In the last 15 years, Phylogenetic Diversity (PD) has gained interest in the
      community of conservation biologists as a surrogate measure for assessing
      biodiversity. We have recently proposed two approaches to select taxa for
      maximizing PD, namely PD with budget constraints and PD on split systems. In this
      paper, we will unify these two strategies and present a dynamic programming
      algorithm to solve the unified framework of selecting taxa with maximal PD under
      budget constraints on circular split systems. An improved algorithm will also be
      given if the underlying split system is a tree.

PMID- 19179697
TI  - Hybridization in nonbinary trees.
AB  - Reticulate evolution--the umbrella term for processes like hybridization,
      horizontal gene transfer, and recombination--plays an important role in the
      history of life of many species. Although the occurrence of such events is widely
      accepted, approaches to calculate the extent to which reticulation has influenced
      evolution are relatively rare. In this paper, we show that the NP-hard problem of
      calculating the minimum number of reticulation events for two (arbitrary) rooted
      phylogenetic trees parameterized by this minimum number is fixed-parameter
      tractable.

PMID- 19179698
TI  - Metrics for phylogenetic networks I: generalizations of the Robinson-Foulds
      metric.
AB  - The assessment of phylogenetic network reconstruction methods requires the
      ability to compare phylogenetic networks. This is the first in a series of papers
      devoted to the analysis and comparison of metrics for tree-child time consistent
      phylogenetic networks on the same set of taxa. In this paper, we study three
      metrics that have already been introduced in the literature: the Robinson-Foulds
      distance, the tripartitions distance and the mu-distance. They generalize to
      networks the classical Robinson-Foulds or partition distance for phylogenetic
      trees. We analyze the behavior of these metrics by studying their least and
      largest values and when they achieve them. As a by-product of this study, we
      obtain tight bounds on the size of a tree-child time consistent phylogenetic
      network.

PMID- 19179699
TI  - Robustness of topological supertree methods for reconciling dense incompatible
      data.
AB  - Given a collection of rooted phylogenetic trees with overlapping sets of leaves,
      a compatible supertree S is a single tree whose set of leaves is the union of the
      input sets of leaves and such that $S$ agrees with each input tree when
      restricted to the leaves of the input tree. Typically with trees from real data,
      no compatible supertree exists, and various methods may be utilized to reconcile
      the incompatibilities in the input trees. This paper focuses on a measure of
      robustness of a supertree method called its "radius" R. The larger the value of R
      is, the further the data set can be from a natural correct tree T and yet the
      method will still output T. It is shown that the maximal possible radius for a
      method is R = 1/2. Many familiar methods, both for supertrees and consensus
      trees, are shown to have R = 0, indicating that they need not output a tree T
      that would seem to be the natural correct answer. A polynomial-time method
      Normalized Triplet Supertree (NTS) with the maximal possible R = 1/2 is defined.
      A geometric interpretation is given, and NTS is shown to solve an optimization
      problem. Additional properties of NTS are described.

PMID- 19179700
TI  - The identifiability of covarion models in phylogenetics.
AB  - Covarion models of character evolution describe inhomogeneities in substitution
      processes through time. In phylogenetics, such models are used to describe
      changing functional constraints or selection regimes during the evolution of
      biological sequences. In this work the identifiability of such models for generic
      parameters on a known phylogenetic tree is established, provided the number of
      covarion classes does not exceed the size of the observable state space. ;Generic
      parameters' as used here means all parameters except possibly those in a set of
      measure zero within the parameter space. Combined with earlier results, this
      implies both the tree and generic numerical parameters are identifiable if the
      number of classes is strictly smaller than the number of observable states.

PMID- 19179701
TI  - Fourier transform inequalities for phylogenetic trees.
AB  - Phylogenetic invariants are not the only constraints on site-pattern frequency
      vectors for phylogenetic trees. A mutation matrix, by its definition, is the
      exponential of a matrix with non-negative off-diagonal entries; this positivity
      requirement implies non-trivial constraints on the site-pattern frequency
      vectors. We call these additional constraints "edge-parameter inequalities". In
      this paper, we first motivate the edge-parameter inequalities by considering a
      pathological site-pattern frequency vector corresponding to a quartet tree with a
      negative internal edge. This site-pattern frequency vector nevertheless satisfies
      all of the constraints described up to now in the literature. We next describe
      two complete sets of edge-parameter inequalities for the group-based models;
      these constraints are square-free monomial inequalities in the Fourier
      transformed coordinates. These inequalities, along with the phylogenetic
      invariants, form a complete description of the set of site-pattern frequency
      vectors corresponding to bona fide trees. Said in mathematical language, this
      paper explicitly presents two finite lists of inequalities in Fourier coordinates
      of the form "monomial < or = 1", each list characterizing the phylogenetically
      relevant semialgebraic subsets of the phylogenetic varieties.

PMID- 19179702
TI  - Maximum parsimony for tree mixtures.
AB  - With the number of sequenced genomes growing ever larger, it is now common
      practice to concatenate sequence alignments from several genomic loci as a first
      step to phylogenetic tree inference. However, as different loci may support
      different trees due to processes such as gene duplication and lineage sorting, it
      is important to better understand how commonly used phylogenetic inference
      methods behave on such "phylogenetic mixtures". Here we shall focus on how
      parsimony, one of the most popular methods for reconstructing phylogenetic trees,
      behaves for mixtures of two trees. In particular, we show that (i) the parsimony
      problem is NP-complete for mixtures of two trees, (ii) there are mixtures of two
      trees that have exponentially many (in the number of leaves) most parsimonious
      trees, and (iii) give an explicit description of the most parsimonious tree(s)
      and scores corresponding to the mixture of a pair of trees related by a single
      TBR operation.

PMID- 19179703
TI  - Drawing rooted phylogenetic networks.
AB  - The evolutionary history of a collection of species is usually represented by a
      phylogenetic tree. Sometimes, phylogenetic networks are used as a means of
      representing reticulate evolution or of showing uncertainty and incompatibilities
      in evolutionary datasets. This is often done using unrooted phylogenetic networks
      such as split networks, due in part, to the availability of software (SplitsTree)
      for their computation and visualization. In this paper we discuss the problem of
      drawing rooted phylogenetic networks as cladograms or phylograms in a number of
      different views that are commonly used for rooted trees. Implementations of the
      algorithms are available in new releases of the Dendroscope and SplitsTree
      programs.

PMID- 19179704
TI  - Consistency of topological moves based on the balanced minimum evolution
      principle of phylogenetic inference.
AB  - Many phylogenetic algorithms search the space of possible trees using topological
      rearrangements and some optimality criterion. FastME is such an approach that
      uses the balanced minimum evolution (BME) principle, which computer studies have
      demonstrated to have high accuracy. FastME includes two variants: balanced
      subtree prune and regraft (BSPR) and balanced nearest neighbor interchange
      (BNNI). These algorithms take as input a distance matrix and a putative
      phylogenetic tree. The tree is modified using SPR or NNI operations,
      respectively, to reduce the BME length relative to the distance matrix, until a
      tree with (locally) shortest BME length is found. Following computer simulations,
      it has been conjectured that BSPR and BNNI are consistent, i.e. for an input
      distance that is a tree-metric, they converge to the corresponding tree. We prove
      that the BSPR algorithm is consistent. Moreover, even if the input contains small
      errors relative to a tree-metric, we show that the BSPR algorithm still returns
      the corresponding tree. Whether BNNI is consistent remains open.

PMID- 19179705
TI  - Refining phylogenetic trees given additional data: an algorithm based on
      parsimony.
AB  - Given a set X of taxa, a phylogenetic X-tree T that is only partially resolved,
      and a collection of characters on X, we consider the problem of finding a
      resolution (refinement) of T that minimizes the parsimony score of the given
      characters. Previous work has shown that this problem has a polynomial time
      solution provided certain strong constraints are imposed on the input. In this
      paper we provide a new algorithm for this problem, and show that it is fixed
      parameter tractable under more general conditions.

PMID- 19179706
TI  - Shrinkage effect in ancestral maximum likelihood.
AB  - Ancestral maximum likelihood (AML) is a method that simultaneously reconstructs a
      phylogenetic tree and ancestral sequences from extant data (sequences at the
      leaves). The tree and ancestral sequences maximize the probability of observing
      the given data under a Markov model of sequence evolution, in which branch
      lengths are also optimized but constrained to take the same value on any edge
      across all sequence sites. AML differs from the more usual form of maximum
      likelihood (ML) in phylogenetics because ML averages over all possible ancestral
      sequences. ML has long been know to be statistically consistent--that is, it
      converges on the correct tree with probability approaching 1 as the sequence
      length grows. However, the statistical consistency of AML has not been formally
      determined, despite informal remarks in a literature that dates back 20 years. In
      this short note we prove a general result that implies that AML is statistically
      inconsistent. In particular we show that AML can 'shrink' short edges in a tree,
      resulting in a tree that has no internal resolution as the sequence length grows.
      Our results apply to any number of taxa.

PMID- 19179707
TI  - Gene classification using codon usage and support vector machines.
AB  - A novel approach for gene classification, which adopts codon usage bias as input
      feature vector for classification by support vector machines (SVM) is proposed.
      The DNA sequence is first converted to a 59-dimensional feature vector where each
      element corresponds to the relative synonymous usage frequency of a codon. As the
      input to the classifier is independent of sequence length and variance, our
      approach is useful when the sequences to be classified are of different lengths,
      a condition that homology-based methods tend to fail. The method is demonstrated
      by using 1,841 Human Leukocyte Antigen (HLA) sequences which are classified into
      two major classes: HLA-I and HLA-II; each major class is further subdivided into
      sub-groups of HLA-I and HLA-II molecules. Using codon usage frequencies, binary
      SVM achieved accuracy rate of 99.3% for HLA major class classification and multi
      class SVM achieved accuracy rates of 99.73% and 98.38% for sub-class
      classification of HLA-I and HLA-II molecules, respectively. The results show that
      gene classification based on codon usage bias is consistent with the molecular
      structures and biological functions of HLA molecules.

PMID- 19179708
TI  - Initializing partition-optimization algorithms.
AB  - Clustering datasets is a challenging problem needed in a wide array of
      applications. Partition-optimization approaches, such as k-means or expectation
      maximization (EM) algorithms, are sub-optimal and find solutions in the vicinity
      of their initialization. This paper proposes a staged approach to specifying
      initial values by finding a large number of local modes and then obtaining
      representatives from the most separated ones. Results on test experiments are
      excellent. We also provide a detailed comparative assessment of the suggested
      algorithm with many commonly-used initialization approaches in the literature.
      Finally, the methodology is applied to two datasets on diurnal microarray gene
      expressions and industrial releases of mercury.

PMID- 19179709
TI  - Structural properties of gene regulatory networks: definitions and connections.
AB  - The study of gene regulatory networks is a significant problem in systems
      biology. Of particular interest is the problem of determining the unknown or
      hidden higher level regulatory signals by using gene expression data from DNA
      microarray experiments. Several studies in this area have demonstrated the
      critical aspect of the network structure in tackling the network modelling
      problem. Structural analysis of systems has proved useful in a number of
      contexts, viz., observability, controllability, fault diagnosis, sparse matrix
      computations etc. In this contribution, we formally define structural properties
      that are relevant to Gene Regulatory Networks. We explore the structural
      implications of certain quantitative methods and explain completely the
      connections between the identifiability conditions and structural criteria of
      observability and distinguishability. We illustrate these concepts in case
      studies using representative biologically motivated network examples. The present
      work bridges the quantitative modelling methods with those based on the
      structural analysis.

PMID- 19179710
TI  - Neonatal Resuscitation Program: first golden minute.

PMID- 19179711
TI  - Mainstreaming early and exclusive breastfeeding for improving child survival.

PMID- 19179712
TI  - Performance evaluation for neonatal phototherapy.

PMID- 19179713
TI  - Hepatitis A - Do we still need new vaccines?

PMID- 19179714
TI  - Effect of sling application on efficacy of phototherapy in healthy term neonates
      with nonhemolytic jaundice: a randomized conrolled trial.
AB  - OBJECTIVE: To evaluate the efficacy of white reflecting material (slings) hung
      from the sides of compact fluorescent lamp (CFL) phototherapy equipment in
      reducing the duration of phototherapy in healthy term neonates with non-hemolytic
      jaundice. DESIGN: Randomized controlled trial. SETTING: Postnatal ward of a
      tertiary level neonatal unit. PARTICIPANTS AND INTERVENTION: Healthy term
      neonates with non-hemolytic jaundice between 24 hours and 10 days of age were
      randomly assigned to receive single surface phototherapy with (n=42) or without
      slings (n=42). OUTCOME MEASURE: Duration of phototherapy in hours (h) and the
      requirement of exchange transfusion. RESULTS: Birthweight (2790+/-352 vs. 2923+/
      330 g), gestation (38+/-1.3 vs. 37+/-1.0 wk) and initial serum total bilirubin
      (STB) (16.6+/-2.4 vs. 16.1+/-2.2 mg/dL) were comparable between the two groups.
      There was no significant difference in the duration of phototherapy (mean+/-SD)
      between the Sling (23.3+/-12.9 h) and No sling (24.9+/-15.4 h) groups (P=0.6).
      The irradiance of photo-therapy equipment (microwatt/cm2, mean+/-SD) was higher
      in Sling group compared to No sling group (195.8+/-24.2 versus 179.7+/-27.7,
      P=0.01). There was a trend towards a higher rate of fall of serum total bilirubin
      (mg/dL, mean +/-SD) in the Sling group (0.23+/-0.49) compared to No sling group
      (0.03+/-0.47) (P=0.06). CONCLUSION: Though hanging of white reflective sling on
      sides of CFL phototherapy equipment resulted in marginal increase in irradiance,
      it did not decrease the duration of phototherapy.

PMID- 19179715
TI  - Immunogenicity and safety of live attenuated hepatitis A vaccine: a multicentric
      study.
AB  - OBJECTIVE: To evaluate immunogenicity and tolerability of single dose live
      attenuated injectable hepatitis A vaccine in four metropolitan cities of India.
      METHODS: Live attenuated hepatitis A vaccine was administered to 505 children
      aged 18 to 60 months in four centers across India. Immunogenicity of the vaccine
      was assessed by estimation of anti-HAV antibody titer at 6 weeks and 6 months
      following administration of the vaccine. Safety evaluation of the vaccine was
      also done during the visits. RESULTS: At 6 weeks, 480 subjects (95%) came for the
      follow-up and 411 (81.4%) subjects reported at the end of 6 months. The geometric
      mean titer (GMT) of anti-HAV antibody of the subjects who did not have the
      seroprotective titer at the baseline were assessed at 6 weeks and 6 months which
      was 81.04 mIU/ml and 150.66 mIU/ml respectively. At 6 weeks, 95.1 % seroconverted
      and at the end of 6 months, 97.9 % had seroconverted. Both solicited and
      unsolicited vaccine-induced local and systemic adverse events were insignificant
      at all the centers, except swelling and induration in a few. CONCLUSION: Live
      attenuated injectable hepatitis A vaccine was immunogenic and tolerable with
      minimal reactogenecity, in this study of single dose schedule. Safety profile was
      also satisfactory in the study population.

PMID- 19179717
TI  - World health report 2008: time to go back to the basics!

PMID- 19179716
TI  - Management of steroid resistant nephrotic syndrome.
AB  - JUSTIFICATION: There is a lack of evidence based guidelines for management of
      children with steroid resistant nephrotic syndrome (SRNS). PROCESS: Experts of
      the Indian Society of Pediatric Nephrology were involved in a two-stage process,
      the Delphi method followed by a structured face to face meeting, to formulate
      guidelines, based on current practices and available evidence, on management of
      these children. Agreement of at least 80% participants formed an opinion.
      OBJECTIVES: To develop specific, realistic, evidence based criteria for
      management of children with idiopathic SRNS. RECOMMENDATIONS: The Expert Group
      emphasized that while all patients with SRNS should initially be referred to a
      pediatric nephrologist for evaluation, the subsequent care might be collaborative
      involving the primary pediatrician and the nephrologist. Following the diagnosis
      of SRNS (lack of remission despite treatment with prednisolone at 2 mg/kg/day for
      4 weeks), all patients (with initial or late resistance) should undergo a renal
      biopsy, before instituting specific treatment. Patients with idiopathic SRNS
      secondary to minimal change disease or focal segmental glomerulosclerosis should
      receive similar therapy. Effective regimens include treatment with calcineurin
      inhibitors (tacrolimus, cyclosporine), intra-venous cyclophosphamide or a
      combination of pulse corticosteroids with oral cyclophosphamide, and tapering
      doses of alternate day corticosteroids. Supportive management comprises of, when
      indicated, therapy with angiotensin converting enzyme inhibitors and statins. It
      is expected that these guidelines shall enable standardization of care for
      patients with SRNS in the country.

PMID- 19179718
TI  - Role of azithromycin in enteric fever.

PMID- 19179719
TI  - Rapid progression of HIV infection in infancy.
AB  - Transmission of HIV from mother to child can occur in utero, during labor or
      after delivery via breast feeding. Data on the fate of babies born with HIV in
      India are scarce. We present details of 25 infants with perinatally acquired HIV
      infection (virologically confirmed) to highlight the observed high rate of
      morbidity and mortality within the first 18 months of life. Our findings of rapid
      disease progression among perinatally infected HIV positive children underline
      the importance of early diagnosis and treatment.

PMID- 19179720
TI  - Urinary iodine excretion levels amongst schoolchildren in Haryana.
AB  - This study was conducted in 2006 to assess the current iodine nutriure of the
      population in Haryana by assessing the urinary iodine excretion levels amongst
      the school age children between 6-12 years. Altogether 3,019 urine samples were
      collected from all the 19 districts in Haryana. The urinary iodine was analyzed
      by using wet digestion method. Less than 1 % of children had urinary iodine
      excretion levels below 20 mcg/L. Percentage of children with urinary iodine
      concentration 21-50 mcg/L, 51-99 mcg/L, and 100 mcg/L were 0.8%, 6.2% and 92.6%
      respectively. We conclude that the Universal Salt Iodization program is being
      successfully implemented in the state as the population has adequate iodine
      status at the time of the survey.

PMID- 19179721
TI  - An outbreak of Serratia marcescens septicemia in neonates.
AB  - Serratia marcescens is a well recognized nosocomial pathogen. We report an
      outbreak with this organism in 8 neonates in a neonatal intensive care unit
      (NICU). Seven cases were treated successfully with meropenem after the failure of
      imipenem treatment. Although they have similar anti-microbial effects, meropenem
      can effectively treat the S. marcescens sepsis resistant to imipenem.

PMID- 19179722
TI  - Biotinidase deficiency with hypertonia as unusual feature.
AB  - We report 3 cases of biotinidase deficiency presenting in early infancy with
      neurological and cutaneous manifestations. All of them had hypertonia
      (spasticity). Response to oral biotin was excellent. One of the cases showed 7D3I
      biotidase deficient mutation.

PMID- 19179723
TI  - Bilateral vocal cord paralysis following treatment with vincristine.
AB  - The neurotoxicity of the vincristine is well known, however, cranial neuropathy
      is not widely recognized. We describe a child with acute lymphoblastic leukemia
      who developed vincristine-induced bilateral vocal cord paralysis. Vocal cord
      paralysis resolved spontaneously upon withdrawal of the vincristine. Vinca
      alkaloid-induced vocal cord paralysis is a potentially dangerous but reversible
      condition.

PMID- 19179724
TI  - Extrahepatic portal hypertension due to familial protein S deficiency.
AB  - Portal vein thrombosis (PVT) is a common cause of portal hypertension in
      children. A majority of children with PVT of unknown etiology have functional
      Protein C deficiency or abnormally elevated levels of anti-cardiolipin
      antibodies. We report an 8 years old Indian girl with portal cavernoma due to
      hereditary Protein S deficiency. We documented familial deficiency of Protein S
      in 2 asymptomatic siblings suggesting that this deficiency is the primary cause
      of portal vein thrombosis.

PMID- 19179725
TI  - Measles with acute disseminated encephalomyelitis (ADEM).
AB  - We report a seven year old male with measles associated acute disseminated
      encephalomyelitis (ADEM) despite having received measles vaccination in infancy.
      The diagnosis was based on serum antimeasles antibodies and MRI brain. The
      patient was managed with high dose corticosteroids along with supportive
      measures. There was a complete neurologically and physica recovery.

PMID- 19179726
TI  - Cold panniculitis neonatorum.

PMID- 19179727
TI  - Intravenous immunoglobulin in Rh hemolytic disease of newborn.

PMID- 19179729
TI  - Cephalosporins with clavulinic acid.

PMID- 19179730
TI  - Audit of measles infection in children from a tertiary hospital.

PMID- 19179733
TI  - End stage renal disease presenting with acute renal failure.

PMID- 19179732
TI  - Why tuberculosis is a difficult disease to target for control or elimination?

PMID- 19179734
TI  - Granulocyte transfusion in children.
AB  - We describe a single institution experience with the use of granulocyte
      transfusion in children. This is a retrospective analysis of 45 collections of
      granulocyte units obtained by apheresis after priming with dexamethasone, infused
      into 17 children with severe neutropenic infections. Ten children survived the
      acute infection. Granulocyte transfusion is a useful adjunct to antimicrobials
      and growth factors in post chemotherapy neutropenic sepsis and is highly
      effective in children with chronic granulomatous disease and life threatening
      infections.

PMID- 19179735
TI  - Transcutaneous bilirubinometry in preterm neonates.
AB  - This prospective study was conducted to evaluate the accuracy of transcutaneous
      bilirubinometry in preterm newborns less than 32 weeks of gestation. Serum
      bilirubin values measured by direct spectrophotometry were considered as
      standard, the range was 2.2-12.5 mg/dL. 32 jaundiced infants of less than 32
      weeks of gestation without phototherapy, including 10 ELBW neonates, were
      enrolled. Close correlation (R=0.933) existed between total serum bilirubin and
      transcutaneous bilirubin values measured over sternum.

PMID- 19179736
TI  - Predisposing factors and outcome of stroke in childhood.
AB  - This prospective study was done to determine the predisposing factors and outcome
      of stroke in Bangladeshi children. It was carried out in Khulna Medical College
      Hospital from July 2002 to June 2007. Admitted children with acute neurological
      deficit attributable to a vascular cause were included in the study. Forty two
      children were finally diagnosed with stroke; 73.8% were male. Apart from
      paresis/paralysis in 35 (83.3%) cases, headache/vomiting/convulsion was the
      presenting problem in 28 (66.7%) cases at the onset. Infection in 17 (40.5%)
      children and trauma in 11 (26.2%) were the important predisposing factors. CT
      scan revealed ischemia and hemorrhage in 18 (42.8% and 8 (19.1%) cases,
      respectively. Twenty two (52.4%) of the children recovered fully and 3 (7.2%)
      expired.

PMID- 19179737
TI  - Bubble CPAP - a primary respiratory support for respiratory distress syndrome in
      newborns.
AB  - In preterm infants with respiratory distress syndrome (RDS), the application of
      continuous positive airway pressure (CPAP) is associated with benefits in terms
      of reduced respiratory failure and reduced mortality. We conducted this
      prospective study to evaluate the effectiveness of bubble-CPAP as primary mode of
      respiratory support. Bubble CPAP was found to be safe and effective means of
      treating mild and moderate grade RDS, it was also observed to be more successful
      in babies born to mothers who had received antenatal steroids.

PMID- 19179738
TI  - Sickle cell anemia in Garasia tribals of Rajasthan.
AB  - Our objective was to document the prevalence of sickle cell anemia among
      scheduled tribe (Garasia) of Sirohi district in Rajasthan state and study the
      clinical and hematological profile of the patients with sickle cell disease (Hb
      SS). In this prospective cross-sectional study, 1676 Garasia tribals attending
      the hospital or the mobile clinic were screened for sickle cell anemia by
      sickling test followed by confirmation with hemoglobin (Hb) electrophoresis.
      Prevalence of sickle cell anemia was found to be 9.2% (155/1676) of which 0.8%
      (14/1676) were homozygous (disease, Hb SS) whereas 8.4% were heterozygous
      (carrier, Hb AS). Common presentations of sickle cell disease were anemia, pain,
      recurrent infection and splenomegaly.

PMID- 19179739
TI  - Cord serum screening test and the newborns allergic status.
AB  - OBJECTIVE: To evaluate the predictive value of a cord serum screen test and
      possible subsequent development of allergic disease in infants. DESIGN: Cohort
      study. SETTING: 100 pregnant women were randomly recruited for the study.
      METHODS: The maternal serum and the cord serum of their matched newborn were
      analyzed for total serum immunoglobulin E (IgE), gamma interferon (g IFN), house
      dust mite- Dermatophagoides pteronyssinus allergen (Der p1) and Blomia tropicalis
      allergen (Blo t5) using immunoassay methods. All infants were followed up for one
      year. RESULTS: Infants who had allergic diseases in the one year follow-up (n=45)
      had significantly (P < 0.001) elevated IgE, Der p1, Blo t5, and significantly low
      g IFN levels in cord serum as compared to the same parameters of infants who did
      not develop allergic disease in the one year follow-up (n=43). CONCLUSION: In
      utero exposure to HDM allergens Der p1 and Blot5 is prevalent. We have
      successfully established a cord serum screening test for predicting allergic
      diseases in infancy with 93% specificity and sensitivity.

PMID- 19179740
TI  - Retinopathy of prematurity in a tertiary care center--incidence, risk factors and
      outcome.
AB  - OBJECTIVE: To study the incidence and risk factors predisposing to retinopathy of
      prematurity (ROP) and to assess the outcome after laser photocoagulation. DESIGN:
      Prospective cohort observational study. SETTING: Infants admitted to a neonatal
      intensive care unit of a referral hospital between 2000-2006 and followed up till
      the age of 3 years. METHODS: Preterm infants with birthweight<1500 g and
      gestation<or=32 weeks were screened for ROP at 4 weeks after birth or 31-33 post
      conceptional age, whichever was later. Infants with birthweight>or=1500 g and
      gestation>32 weeks were screened only if they had additional risk factors. Those
      found to have threshold disease ROP had laser photocoagulation. They were
      recalled at 3 years and had a complete ophthalmic check up. RESULTS: The
      incidence of ROP in the 552 infants who were screened was 22.3%. No ROP was found
      in infants weighing>or=2000 g or with a gestational age more than 36 weeks. Risk
      factors predisposing to ROP were septicemia (P<0.001), apnea (P=0.0001) and
      oxygen therapy (P=0.031). Out of the 123 infants who had ROP, 41 (33.6%) needed
      laser photocoagulation. Twenty two (53.6%) were seen at 3 years of age. Ten
      children had myopia, 1 had amblyopia and 9 children had completely normal
      structural and visual outcome. Only two (9%) children were blind due to retinal
      detachment. CONCLUSION: One third of the infants with ROP needed laser
      photocoagulation, the outcome of which was good. Risk factors predisposing to ROP
      were septicemia, apnea, oxygen therapy and use of blood products.

PMID- 19179741
TI  - Hemoglobin a1c levels in children with asthma using low dose inhaled
      corticosteroids.
AB  - OBJECTIVES: Steroids may raise the blood glucose levels as a systemic effect. Due
      to this, the potential effect of prophylactic use of inhaled steroids (ICS) on
      HbA1c levels in children with asthma was investigated. STUDY DESIGN: Case control
      study. ? SETTING: Outpatient department. PARTICIPANTS: 141 children with asthma
      but without diabetes (study group) and 52 children without diabetes or asthma
      (control group). MAIN OUTCOME MEASURE: HbA1c levels. RESULTS: The mean age of the
      study group (n=141) was 6.6?3.0 years and comprised 70 females (50% of the group)
      and 71 males. The mean age of the control group (n=52) was 7.1?3.0 years, and
      comprised 24 females (46%) and 28 males (54%). Age and sex differences between
      the groups were not significant. The mean HbA1c value was 5.44?0.75% among the
      children with asthma and 5.14?0.41% in the control group. HbA1c levels in
      children with asthma was significantly higher than the control group (P=0.006).
      No significant correlation was found between cumulative dose of ICS and HbA1c
      levels. Similarly, levels of HbA1c did not change with increased time of usage of
      ICS (P=0.96). CONCLUSION: Asthmatic children who are taking low doses of ICS have
      higher HbA1c values than healthy children.

PMID- 19179742
TI  - Hospital management of severely malnourished children: comparison of locally
      adapted protocol with WHO protocol.
AB  - OBJECTIVES: To compare the effectiveness of locally adapted Institute of Child
      and Mother Health (ICMH) protocol with the WHO protocol for the management of
      severely malnourished children in Bangladesh. DESIGN: Quasi-experimental non
      randomized clinical trial. SETTING: Hospital based. PARTICIPANTS: Severely
      malnourished children (2-59 mo) with weight for height<70% (n=60). INTERVENTION:
      Children treated with either WHO protocol (Group I, n=30) or ICMH protocol (Group
      II, n=30). OUTCOME VARIABLES: Clinical improvement, weight gain, time taken to
      achieve target weight gain, and mortality among the study subjects. RESULTS: Mean
      (SD) weight related to gain in Group I and Group II was 11.2 (4.1) and 11.1 (3.9)
      g/kg/day, respectively. The weight gain was not related to the age group or type
      of malnutrition. The time taken for edema to subside (7.3 d vs 8 d) and for
      improvement of appetite (6.5 d to 7.3 d vs 6.7 d to 8.4 d) was similar between
      the groups. The target weight gain was achieved in 28.3 (11.5) days in Group I
      against 27.9 (6.2) days in Group II (P=0.88). The mortality rate was 6.7% in each
      group. CONCLUSION: Treatment of severe malnutrition with locally adapted ICMH
      protocol using locally available foods is as efficacious as the WHO protocol.

PMID- 19179743
TI  - Comparison of Ready-to-Use Therapeutic Food with cereal legume-based khichri
      among malnourished children.
AB  - OBJECTIVE: To compare the acceptability and energy intake of Ready-to-Use
      Therapeutic Food (RUTF) with cereal legume based khichri among malnourished
      children. DESIGN: An acceptability trial with cross-over design. SETTING: Urban
      low to middle socioeconomic neighbor-hoods in Delhi. SUBJECTS: 31 children aged >
      or =6 to < or =36 months with malnutrition, defined as Weight for height (WHZ) < 
      2 to > or = -3 SD, with no clinical signs of infection or edema. INTERVENTION:
      Children were offered weighed amounts of RUTF and khichri in unlimited amounts
      for 2 days, one meal of each on both days. Water was fed on demand. Caregivers
      interviews and observations were conducted on the second day. OUTCOME MEASURES:
      Acceptability of RUTF compared to khichri based on direct observation and energy
      intake for test and control meals. RESULTS: The proportion of children who
      accepted RUTF eagerly was 58% as against 77% for khichri. 42% children on RUTF
      and 23% on khichri accepted the meal but not eagerly. The median (IQR) energy
      intake over the two day period in children aged 6 to 36 months from RUTF was 305
      (153, 534) kcal, and from khichri was 242 (150, 320) kcal (P=0.02). CONCLUSION:
      RUTF and khichri were both well accepted by study children. The energy intake
      from RUTF was higher due to its extra energy density.

PMID- 19179744
TI  - Clinical profile of group A meningococcal outbreak in Delhi.
AB  - We present a retrospective analysis of clinical profile of 100 children admitted
      to a Government hospital at Delhi between April 2005 and December 2006 with group
      A meningococcal infection. Maximum children presented in late winter and spring.
      Younger children were less affected (5% children < 1 year). Fever (86%), vomiting
      (64%) and rash (63%) were the most common presenting symptoms. All children
      presented within 5 days of onset of symptoms and 52% within 24 hours. 67 %
      children had meningococcal meningitis; 20% had meningococcemia; and 13% had both.
      Overall mortality was 17%. Altered sensorium and shock at presentation
      significantly increased the mortality. All culture positive cases had group A
      Neisseria meningitides. All meningococcal isolates were sensitive to
      penicillin/ampicillin, ciprofloxacin, ceftriaxone, chloramphenicol and
      erythromycin except, one each resistant to ampicillin and erythromycin.

PMID- 19179745
TI  - Early identification of autism.
AB  - This study was carried out to determine the nature and timing of parents initial
      concerns and their subsequent help seeking behavior, so as to suggest ways to
      facilitate early identification of autism. The introductory part of the Autism
      Diagnostic Interview-Revised was used in a survey to elicit relevant information
      from parents of autistic children. Delayed/deviant speech and language
      development was the commonest early concern of parents. The mean age of parental
      recognition of any problem was 23.4 months. The mean time lag from first
      recognition of the problem to seeking professional help was 4 months and to
      diagnosis, 32 months. In 68 % of cases, the first professional consulted was a
      child specialist.

PMID- 19179746
TI  - Fetal heart rate variability reveals differential dynamics in the intrauterine
      development of the sympathetic and parasympathetic branches of the autonomic
      nervous system.
AB  - The aim of this study was to investigate the hypothesis that fetal beat-to-beat
      heart rate variability (fHRV) displays the different time scales of sympatho
      vagal development prior to and after 32 weeks of gestation (wks GA). Ninety-two
      magnetocardiograms of singletons with normal courses of pregnancy between 24 + 1
      and 41 + 6 wks GA were studied. Heart rate patterns were either quiet/non
      accelerative (fHRP I) or active/accelerative (fHRP II) and recording quality
      sufficient for fHRV. The sample was divided into the GA groups <32 wks GA/>32 wks
      GA. Linear parameters of fHRV were calculated: mean heart rate (mHR), SDNN and
      RMSSD of normal-to-normal interbeat intervals, power in the low (0.04-0.15 Hz)
      and high frequency range (0.15-0.4 Hz) and the ratios SDNN/RMSSD and LF/HF as
      markers for sympatho-vagal balance. fHRP I is characterized by decreasing
      SDNN/RMSSD, LF/HF and mHR. The decrease is more pronounced <32 wks GA. Beyond
      that GA SDNN/RMSSD is predominantly determined by RMSSD during fHRP I and by SDNN
      during fHRP II. In contrast to fHRP I, during fHRP II, mHR is positively
      correlated to SDNN/RMSSD instead of SDNN >32 wks GA. LF/HF increases in fHRP II
      during the first half of the third trimester. Non-accelerative fHRP are
      indicative of parasympathetic dominance >32 wks GA. In contrast, the sympathetic
      accentuation during accelerative fHRP is displayed in the interrelations between
      mHR, SDNN and SDNN/RMSSD. Prior to 32 wks GA, fHRV reveals the increasing
      activity of the respective branches of the autonomic nervous system
      differentiating the types of fHRP.

PMID- 19179747
TI  - Spontaneous baroreflex sensitivity estimates during graded bicycle exercise: a
      comparative study.
AB  - In the literature, several methods have been proposed for the assessment of the
      baroreflex sensitivity from spontaneous variability of heart period and systolic
      arterial pressure. The present study compares the most utilized approaches for
      the evaluation of the spontaneous baroreflex sensitivity (i.e. sequence-based,
      spectral, cross-spectral and model-based techniques) over a protocol capable of
      inducing a progressive decrease of the baroreflex sensitivity in the presence of
      a relevant respiratory drive (i.e. a stepwise dynamic bicycle exercise at 10%,
      20% and 30% of the maximum nominal individual effort) in 16 healthy humans.
      Results demonstrated that the degree of correlation among the estimates is
      related to the structure of the model explicitly or implicitly assumed by the
      method and depends on the experimental condition (i.e. on the physiological
      mechanisms contemporaneously active with baroreflex, e.g. cardiopulmonary
      reflexes). However, even in the presence of a significant correlation,
      proportional and/or constant biases can be present, thus rendering spontaneous
      baroreflex estimates not interchangeable. We suggest that the comparison among
      different baroreflex sensitivity estimates might elucidate physiological
      mechanisms responsible for the relationship between heart period and systolic
      arterial pressure.

PMID- 19179748
TI  - Monitoring the energy status of a living organism in real time.

PMID- 19179749
TI  - The Indian genetic landscape and disease-related genes.

PMID- 19179750
TI  - Neuronal modulation of the immune response.

PMID- 19179751
TI  - Visual object recognition: building invariant representations over time.

PMID- 19179752
TI  - Multifactorial etiology of Kaposi' sarcoma: a hypothesis.

PMID- 19179753
TI  - Getting hooked on thyroid hormone action: a semi-autobiographical account.

PMID- 19179754
TI  - What history tells us XV. Cyril Norman Hinshelwood (1897-1967) - a chemical
      dynamic vision of the organic world.

PMID- 19179755
TI  - Three novel single-nucleotide polymorphisms of the bovine LHX3 gene.
AB  - The LHX3 gene encodes LIM homeodomain class transcription factors that have
      important roles to play in pituitary and nervous system development.On the one
      hand,mutations of LHX3 are associated with deficiencies of growth hormone
      (GH),prolactin (PRL),luteotrophic hormone (LH),follicle-stimulating hormone
      (FSH)and thyroid- stimulating hormone (TSH);on the other hand,mutations of LHX3
      are also associated with combined pituitary hormone deficiency (CPHD) diseases in
      human and animal models.To date,few polymorphisms of the bovine LHX3 gene have
      been reported.In this study,polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP)and DNA sequencing methods were employed to screen the
      genetic variations within the bovine LHX3 gene in 802 Chinese indigenous
      cattle.The results revealed three novel single-nucleotide polymorphisms (SNPs):
      AY923832: g.7553G >A, 7631C>T and 7668C>G.Among them,a synonymous mutation of
      exon II was identified: GAG ((Glu)> GAA (Glu) at position 72 aa
      (AY923832:g.7553G>A) of LHX3 ((403aa) in the four Chinese bovine
      breeds.Significant statistical differences in genotypic frequencies for exon II
      and its flanking region of the LHX3 gene implied that the polymorphic locus was
      significantly associated with cattle breeds by the X2-test (X2=68.975,df=6, P
      <0.001).Hence,the three novel SNPs not only extend the spectrum of genetic
      variations of the bovine LHX3 gene, but could also possibly contribute to
      conducting association analysis and evaluating these as genetic markers in bovine
      breeding and genetics,and CPHD detection.

PMID- 19179756
TI  - Cloning and characterization of a novel cysteine protease gene (HbCP1) from Hevea
      brasiliensis.
AB  - The full-length cDNA encoding a cysteine protease,designated HbCP1, was isolated
      for the first time from Hevea brasiliensis by the rapid amplification of cDNA
      ends (RACE) method. HbCP1 contained a 1371 bp open reading frame encoding 457
      amino acids.The deduced HbCP1 protein,which showed high identity to cysteine
      proteases of other plant species,was predicted to possess a putative repeat in
      toxin (RTX) domain at the N-terminal and a granulin (GRAN) domain at the C
      terminal.Southern blot analysis indicated that the HbCP1 gene is present as a
      single copy in the rubber tree.Transcription pattern analysis revealed that HbCP1
      had high transcription in laticifer,and low transcription in bark and leaf.The
      transcription of HbCP1 in latex was induced by ethylene and tapping.Cloning of
      the HbCP1 gene will enable us to further understand the molecular
      characterization of cysteine protease and its possible function in the rubber
      tree.

PMID- 19179757
TI  - Homology modelling and bivalent single-chain Fv construction of anti-HepG2 single
      chain immunoglobulin Fv fragments from a phage display library.
AB  - We prepared single-chain immunoglobulin Fv fragments (scFv) SLH10 specific for
      the HepG2 cell line after biopanning from a large human-naive phage display
      library (Griffin. 1 Library). The three-dimensional (3D) structure of SLH10 was
      modelled by the Insight II molecule simulation software.The structure was refined
      using the molecular dynamics method.The structures with the least steric clashes
      and lowest energy were determined finally. The optimized structures of heavy (VH)
      and light (VL) variable chains of SLH10 scFv were obtained.Then SLH10 bivalent
      single-chain Fv (BsFv) was constructed that would be suitable for high-affinity
      targeting.SLH10 BsFv was generated by linking scFvs together and identified by
      sequencing. Its expression products were confirmed by western blot analysis.The
      relative molecular masses of scFv and BsFv were approximately 30 kDa and 60
      kDa,respectively. Flow cytometry revealed that SLH10 BsFv bound the selected cell
      lines with greater signal intensity than the parental scFv. The improved antigen
      binding of SLH10 BsFv may be useful for immunodiagnostics or targeted gene
      therapy for liver cancer.

PMID- 19179758
TI  - Comparative docking studies of CYP1b1 and its PCG-associated mutant forms.
AB  - Molecular docking has been used to compare and contrast the binding modes of
      oestradiol with the wild-type and some disease-associated mutant forms of the
      human CYP1b1 protein.The receptor structures used for docking were derived from
      molecular dynamics simulations of homology-modelled structures. Earlier studies
      involving molecular dynamics and principal component analysis indicated that
      mutations could have a disruptive effect on function,by destabilizing the native
      properties of the functionally important regions, especially those of the haem
      binding and substrate-binding regions,which constitute the site of catalytic
      activity of the enzyme.In order to gain more insights into the possible
      differences in substrate-binding and catalysis between the wild-type and mutant
      proteins,molecular docking studies were carried out. Mutants showed altered
      protein -ligand interactions compared with the wild-type as a consequence of
      changes in the geometry of the substrate-binding region and in the position of
      haem relative to the active site. An important difference in ligand -protein
      interactions between the wild-type and mutants is the presence of stacking
      interaction with phenyl residues in the wild-type,which is either completely
      absent or considerably weaker in mutants.The present study revealed essential
      differences in the interactions between ligand and protein in wild-type and
      disease mutants,and helped in understanding the deleterious nature of disease
      mutations at the level of molecular function.

PMID- 19179759
TI  - Proteomic analysis of cervical cancer cells treated with suberonylanilide
      hydroxamic acid.
AB  - Suberonylanilide hydroxamic acid (SAHA)is an orally administered histone
      deacetylase inhibitor (HDACI) that has shown significant antitumour activity in a
      variety of tumour cells.To identify proteins involved in its antitumour
      activity,we utilized a proteomic approach to reveal protein expression changes in
      the human cervical cancer cell line HeLa following SAHA treatment.Protein
      expression profiles were analysed by 2-dimensional polyacrylamide gel
      electrophoresis (2-DE) and protein identification was performed on a MALDI-Q-TOF
      MS/MS instrument.As a result,a total of nine differentially expressed proteins
      were visualized by 2-DE and Coomassie brilliant blue (CBB) staining.Further,all
      the changed proteins were positively identified via mass spectrometry (MS)/MS
      analysis. Of these,PGAM1 was significantly downregulated in HeLa cells after
      treatment with SAHA. Moreover,PGAM1 has been proven to be downregulated in
      another cervical cancer cell line (CaSki) by western blot analysis.Together,using
      proteomic tools,we identified several differentially expressed proteins that
      underwent SAHA-induced apoptosis. These changed proteins may provide some clues
      to a better understanding of the molecular mechanisms underlying SAHA-induced
      apoptosis in cervical cancer.

PMID- 19179760
TI  - Redifferentiation of human hepatoma cells (SMMC-7721) induced by two new highly
      oxygenated bisabolane-type sesquiterpenes.
AB  - Bisabolane-type sesquiterpenes are a class of biologically active compounds that
      has antitumour,antifungal, antibacterial,antioxidant and antivenom properties.We
      investigated the effect of two new highly oxygenated bisabolane-type
      sesquiterpenes (HOBS)isolated from Cremanthodium discoideum (C.discoideum) on
      tumour cells. Our results showed that HOBS induced morphological differentiation
      and reduced microvilli formation on the cell surface in SMMC-7721 cells.Flow
      cytometry analysis demonstrated that HOBS could induce cell-cycle arrest in the
      G1 phase. Moreover,HOBS was able to increase tyrosine-alpha ketoglutarate
      transaminase activity,decrease alpha- foetoprotein level and gamma-glutamyl
      transferase activity. In addition,we found that HOBS inhibited the anchorage-
      independent growth of SMMC-7721 cells in a dose-dependent manner.Taken
      together,all the above observations indicate that HOBS might be able to normalize
      malignant SMMC-7721 cells by inhibiting cell proliferation and inducing
      redifferentiation.

PMID- 19179761
TI  - Drosophila-based in vivo assay for the validation of inhibitors of the epidermal
      growth factor receptor/Ras pathway.
AB  - Overexpression of epidermal growth factor receptor (EGFR) is a common phenomenon
      observed in most cancers. Clinical treatment of such cancer involves the use of
      chemotherapeutic agents such as ge ? tinib and erlotinib which are inhibitors of
      tyrosine kinase (TK). These small molecules bind to the ATP-binding sites of the
      TK domain of EGFR.Our in silico analysis suggests that the TK domains of
      Drosophila and human EGFR are highly conserved. We therefore employed the
      Drosophila system to validate the in silico observations made with two important
      anticancer drugs.Since a large number of mutant flies are available,it was
      possible to investigate the various components of the EGFR/Ras/Raf/MAPK pathways
      and the phosphorylation status of diphosphorylated extracellular signal-regulated
      kinase (dp-ERK1/2). These studies confirm the binding of the anilinoquinazolines
      to the Drosophila EGFR protein and modulation of its activity. Thus,Drosophila
      appears to be a robust and simple model system for screening newer anticancer
      drugs that act as TK inhibitors (TKIs).

PMID- 19179762
TI  - Numerical exploration of the influence of neural noise on the psychometric
      function at low stimulation intensity levels.
AB  - The relationship between stimulus intensity and the probability of detecting the
      presence of the stimulus is described by the psychometrical function.The
      probabilistic nature of this relationship is based on the stochastic behaviour of
      sensory neural channels and sensory networks involved in perceptual processing
      (Kiang 1968). This study tries to establish a continuum of variability across
      different levels of integration in the central nervous system. Once the opening
      and closing times of ionic channels was simulated, a threshold to the collective
      behaviour of voltage-gated ionic channels was imposed in order to generate the
      spike train of a single neuron. Afterwards,the trains of spikes of different
      neurons were added up,simulating the activity of a sensory nerve. By adding the
      activity due to the stimulus to the spontaneous neural behaviour,the psychometric
      function was simulated using a thresholding approach.The results can replicate
      the stochastic resonance phenomenon, but also open up the possibility that
      attentional phenomena can be mediated not only by increasing neural activity
      (bursting or oscillatory),but also by increasing noise at the neural level.

PMID- 19179763
TI  - Inherent rhythmicity and interstitial cells of Cajal in a frog vein.
AB  - Interstitial cells of Cajal are responsible for rhythmic contractions of the
      musculature of the gastrointestinal tract and blood vessels.The existence of
      these cells and spontaneous rhythmicity were noticed in amphibian vein and the
      findings are reported in this paper.The postcaval vein was identified in the
      frog, Rana tigrina and was perfused with amphibian Ringer solution after
      isolation.Contractile activity was recorded through a tension transducer
      connected to a polygraph.The isolated postcaval vein showed spontaneous rhythmic
      activity. Addition of cold Ringer solution decreased, while warm Ringer
      increased, the rate of contraction. Adrenaline caused inhibition of rhythmic
      activity at a dosage that increased the rate of isolated sinus venosus.Sections
      of the postcaval vein,when stained supravitally with methylene blue, showed the
      presence of interstitial cells of Cajal. Photic stimulation of the vein in the
      presence of methylene blue led to a significant decrease in the rate of
      spontaneous beating of the vein.These findings indicate that the postcaval vein
      of frog is capable of inherent rhythmcity, which is dependent on the interstitial
      cells of Cajal but is independent of the sinus venosus.

PMID- 19179764
TI  - Primate numts and reticulate evolution of capped and golden leaf monkeys
      (Primates: Colobinae).
AB  - A recent phylogenetic study of langurs and leaf monkeys of South Asia suggested a
      reticulate evolution of capped and golden leaf monkeys through ancient
      hybridization between Semnopithecus and Trachypithecus .To test this
      hybridization scenario, I analysed nuclear copies of the mitochondrial cytochrome
      b gene (numts) from capped,golden and Phayre's leaf monkeys. These numts were
      aligned with mitochondrial cytochrome b sequences of various species belonging to
      the genera Semnopithecus and Trachypithecus .In the phylogenetic tree derived
      from this alignment,the numts fell into three distinct clades (A,B and C)
      suggesting three independent integration events.Clade A was basal to
      Semnopithecus, and clades B and C were basal to Trachypithecus. Among the numts
      in clades A and C were sequences derived from species not represented in their
      respective sister mitochondrial groups.This unusual placement of certain numts is
      taken as additional support for the hybridization scenario. Based on the
      molecular dating of these integration events,hybridization is estimated to have
      occurred around 7.1 to 3.4 million years ago.Capped and golden leaf monkeys might
      have to be assigned to a new genus to reconcile their unique evolutionary
      history. Additionally, northeast India appears to be a 'hot spot' for lineages
      that might have evolved through reticulate evolution.

PMID- 19179765
TI  - Branch-point stoichiometry can generate weak links in metabolism: the case of
      glycine biosynthesis.
AB  - Although the metabolic network permits conversion between almost any pair of
      metabolites,this versatility fails at certain sites because of chemical
      constraints (kinetic,thermodynamic and stoichiometric) that seriously restrict
      particular conversions. We call these sites weak links in metabolism,as they can
      interfere harmfully with management of matter and energy if the network as a
      whole does not include adequate safeguards. A critical weak link is created in
      glycine biosynthesis by the stoichiometry of the reaction catalyzed by glycine
      hydroxymethyltransferase (EC 2.1.2.1), which converts serine into glycine plus
      one C1 unit: this produces an absolute dependence of the glycine production flux
      on the utilization of C1 units for other metabolic pathways that do not work
      coordinately with glycine use. It may not be possible,therefore,to ensure that
      glycine is always synthesized in sufficient quantities to meet optimal metabolic
      requirements.

PMID- 19179766
TI  - The neural crest and neural crest cells: discovery and significance for theories
      of embryonic organization.
AB  - The neural crest has long fascinated developmental biologists,and,increasingly
      over the past decades,evolutionary and evolutionary developmental biologists.The
      neural crest is the name given to the fold of ectoderm at the junction between
      neural and epidermal ectoderm in neurula-stage vertebrate embryos.In this
      sense,the neural crest is a morphological term akin to head fold or limb bud.This
      region of the dorsal neural tube consists of neural crest cells,a special
      population(s)of cell,that give rise to an astonishing number of cell types and to
      an equally astonishing number of tissues and organs.Neural crest cell
      contributions may be direct - providing cells - or indirect - providing a
      necessary, often inductive, environment in which other cells develop.The enormous
      range of cell types produced provides an important source of evidence of the
      neural crest as a germ layer, bringing the number of germ layers to four -
      ectoderm,endoderm,mesoderm,and neural crest. In this paper I provide a brief
      overview of the major phases of investigation into the neural crest and the major
      players involved,discuss how the origin of the neural crest relates to the origin
      of the nervous system in vertebrate embryos,discuss the impact on the germ-layer
      theory of the discovery of the neural crest and of secondary neurulation,and
      present evidence of the neural crest as the fourth germ layer.A companion paper
      (Hall, Evol. Biol.2008) deals with the evolutionary origins of the neural crest
      and neural crest cells.

PMID- 19179768
TI  - Nicorandil attenuates FeCl(3)-induced thrombus formation through the inhibition
      of reactive oxygen species production.
AB  - BACKGROUND: Although nicorandil has a number of beneficial cardiovascular
      actions, its effects on endothelial cells in the context of thrombosis have not
      been elucidated. METHODS AND RESULTS: Arterial thrombosis was induced by
      endothelial injury caused by FeCl(3) in the mouse testicular artery. Thrombus
      growth led to complete occlusion 12 min after endothelial injury in control mice.
      The antiplatelet agent, tirofiban, and nicorandil significantly slowed the growth
      of thrombi, resulting in arterial occlusion after 58 min and 55 min,
      respectively. In the absence of endothelial cells, nicorandil did not inhibit
      platelet aggregation. Diazoxide and high-dose isosorbide dinitrate both showed a
      similar effect to that of nicorandil. The beneficial effect of nicorandil was
      prevented by 5-hydroxydecanoate, but not by L-NAME. The production of reactive
      oxygen species by FeCl(3) treatment was measured with the specific fluorescent
      probe, dihydrorhodamine 123. After FeCl(3) treatment, nicorandil significantly
      inhibited the increase in fluorescence. In further experiments, incubation of
      human umbilical vein endothelial cells with nicorandil did not change the
      endothelial nitric oxide synthase (eNOS) mRNA levels, eNOS phosphorylation or
      nitrite production. CONCLUSIONS: Nicorandil attenuates FeCl(3)-induced thrombus
      formation in the mouse testicular artery, which suggests that it may inhibit the
      generation of reactive oxygen species by FeCl(3)-treated endothelial cells
      through activation of the mitochondrial ATP-sensitive potassium channels.

PMID- 19179767
TI  - Bacterial persistence: some new insights into an old phenomenon.
AB  - Bigger discovered more than 60 years ago,at the very beginning of the antibiotic
      era,that populations of antibiotic-sensitive bacteria contained a very small
      fraction (approximately 10 ;-6 )of antibiotic-tolerant cells (persisters).
      Persisters are different from antibiotic-resistant mutants in that their
      antibiotic tolerance is non-heritable and reversible.In spite of its importance
      as an interesting biological phenomenon and in the treatment of infectious
      diseases,persistence did not attract the attention of the scientific community
      for more than four decades since its discovery.The main reason for this lack of
      interest was the difficulty in isolating sufficient numbers of persister cells
      for experimentation,since the proportion of persisters in a population of wild
      type cells is extremely small. However, with the discovery of high-persister
      (hip) mutants of Escherichia coli by Moyed and his group in the early 1980s,the
      phenomenon attracted the attention of many groups and significant progress has
      occurred since then.It is now believed that persistence is the end result of a
      stochastic switch in the expression of some toxin-antitoxin (TA) modules (of
      which the hipA and hipB genes could be examples),creating an imbalance in their
      intracellular levels. There are also models invoking the involvement of the
      alarmone (p) ppGpp in the generation of persisters.However,the precise mechanisms
      are still unknown. Bacterial persistence is part of a wider gamut of phenomena
      variously called as bistability, multistability, phenotypic
      heterogeneity,stochastic switching processes,etc.It has attracted the attention
      of not only microbiologists but also a diverse band of researchers such as
      biofilm researchers, evolutionary biologists,sociobiologists,etc.In this
      article,I attempt to present a broad overview of bacterial persistence to
      illustrate its significance and the need for further exploration.

PMID- 19179769
TI  - Electrophysiological characteristics of the Marshall potential in dogs.
AB  - BACKGROUND: The electrophysiological characteristics of the Marshall potential is
      important in ligament of Marshall (LOM) ablation. METHODS AND RESULTS: Marshall
      potential was recorded under sinus rhythm and left atrial appendage (LAA) pacing
      and in the first randomly selected 5 dogs (Group 1), LOM ablation was performed.
      Histological examination was performed in the remaining 10 dogs, which were
      subdivided according to the results (Groups 2, 3). During LAA pacing in Group 2,
      the AM interval was prolonged or shortened, whereas in Group 3 it was prolonged
      (125+/-9 vs 80+/-6 ms, P=0.043, when the pacing rate =350) (126+/-9 vs 80+/-6 ms,
      P=0.0442, when the pacing rate =450). The Marshall potential was separated from
      the atrial electrogram by LAA pacing in Groups 2 and 3. There was no significant
      difference in the AM interval during sinus rhythm and right atrial appendage
      pacing. CONCLUSIONS: Marshall potential has different forms on electrograms,
      including a prolonged AM interval, which presents with LAA pacing. This finding
      might be useful in LOM ablation.

PMID- 19179770
TI  - Aortic pulse wave velocity predicts cardiovascular mortality in middle-aged and
      elderly Japanese men.
AB  - BACKGROUND: Aortic pulse wave velocity (PWV) is widely used as a noninvasive
      index of arterial stiffness and was used in the present study to investigate the
      relationship between PWV and cardiovascular mortality in the middle-aged and
      elderly Japanese population using a longitudinal study design. METHODS AND
      RESULTS: From 1988 to 2003, a total of 3,960 men (50-69 years old at baseline)
      who underwent medical check-ups and measurement of PWV, which was standardized
      for diastolic blood pressure, were recruited and divided into 4 groups according
      to the PWV values. The average follow-up period was 8.2 years. Mortality from all
      causes and from cardiovascular disease significantly increased as PWV increased
      in the entire follow-up period. Multivariate-adjusted relative risks of all-cause
      and cardiovascular disease mortality for the highest quartile of PWV (>9.0 m/s)
      were 1.28 (95% confidence interval (CI) 0.97-1.68) and 1.83 (95%CI 1.02-3.29),
      respectively, compared with the lowest quartile (<7.5 m/s). CONCLUSIONS: An
      increased PWV can predict cardiovascular mortality in middle-aged and elderly
      Japanese men.

PMID- 19179771
TI  - Important regulatory role of activated platelet-derived procoagulant activity in
      the propagation of thrombi formed under arterial blood flow conditions.
AB  - BACKGROUND: The functional links between the activation of platelets and the
      coagulation system have not been clarified. METHODS AND RESULTS: Immobilized
      collagen fibrils were perfused with human blood containing fluoresceinated
      platelets in the presence of various concentrations of thrombin inhibitor.
      Coagulant activity around platelet thrombi was detected using a FITC-conjugated
      antibody against the fibrin monomer complex (F-405). Intra-cytosolic calcium ion
      concentrations ([Ca(2+)](i)) in individual platelets and the volume of thrombi
      were detected with an ultrafast confocal laser microscope equipped with a piezo
      motor control unit. The volume of platelet thrombi formed after 8 min of blood
      perfusion in the presence of 10, 25, 50, and 100 micromol/L argatroban was 7.69+/
      0.46 microm(3), 6.61+/-1.96 microm(3), 3.63+/-1.54 microm(3), and 1.67+/-0.75
      microm(3), respectively. There was a positive correlation between the volume of
      platelet thrombi and the amount of fibrin monomer complex produced around them.
      The [Ca(2+)](i) of the platelets forming the thrombi oscillated between a minimum
      of 92.0+/-57.4 nmol/L, 120.1+/-68.1 nmol/L, and a maximum of 217.6+/-131.5
      nmol/L, 367.6+/-189.1 nmol/L, respectively, in the presence of 100 and 10 mumol/L
      argatroban. CONCLUSIONS: The results suggest a crucial role of coagulant activity
      in both the generation of fibrin and the growth of platelet thrombi.

PMID- 19179772
TI  - Health-related quality of life in patients with coronary heart disease after
      residential vs ambulatory cardiac rehabilitation.
AB  - BACKGROUND: The aim of this study was to evaluate the influence of residential
      (RCR) vs ambulatory (ACR) cardiac rehabilitation (CR) on health-related quality
      of life (QOL) connected with changes in exercise capacity of patients with
      coronary heart disease (CHD). METHODS AND RESULTS: The 562 patients with CHD were
      studied: 313 participants in RCR and 249 participants in ACR. The examination was
      performed at the beginning of CR and after 8 weeks. QOL was assessed using the
      EuroQuol 5D (EQ-5D) and SF36 questionnaires. Exercise testing was performed with
      evaluation of workload during the last stage of the test and rate of perceived
      exertion intensity. In the first examination, patients from both groups did not
      differ significantly. After 8 weeks, a similar improvement in QOL was observed in
      both settings of CR according to EQ-5D and SF36 results. Health status was
      improved by 11.1% in the RCR group and by 10.4% in the ACR group. Last workload's
      intensity increased significantly by 32.1% in the RCR group and by 38.1% in the
      ACR group. The rate of perceived exertion intensity did not change despite the
      bigger workloads during the exercise test. CONCLUSIONS: Comprehensive CR improves
      health-related QOL and exercise capacity without differences between residential
      and ambulatory models.

PMID- 19179773
TI  - Long-term epoprostenol therapy in pulmonary artery hypertension.
AB  - BACKGROUND: Sequential changes in the hemodynamic effect of chronic epoprostenol
      therapy raise the following questions. Does an increase in cardiac output (CO)
      precede lowering of the pulmonary artery pressure (PAP) over the time course of
      improvement? What are the characteristics of good responders to chronic
      epoprostenol treatment? METHODS AND RESULTS: Hemodynamics were evaluated by
      catheter examination. Most patients still alive after >1 year showed an increase
      in CO either with no change in mean PAP or accompanied by a decrease in mean PAP
      during increased dosing of epoprostenol. Immediately before cessation of the
      increase in epoprostenol dose in good responders, the ratio of total pulmonary
      resistance to total systemic resistance was low, and the pulmonary artery wedge
      pressure minus right atrial pressure was high compared with the newest data in
      poor responders. One year after fixing at the best dose of epoprostenol, the mean
      PAP further decreased. CONCLUSIONS: In good responders, pulmonary selectivity to
      epoprostenol is high, and the blood returning to the left-sided heart through the
      pulmonary circulation increases. Hemodynamics further improve, even after fixing
      at the best dose of epoprostenol. The present data did not show that an increase
      in CO precedes lowering of the PAP over the course of improvement.

PMID- 19179774
TI  - Metabolic syndrome and risk of recurrence of atrial fibrillation after catheter
      ablation.
AB  - BACKGROUND: Metabolic syndrome (MetS), as well as several risk factors of
      cardiovascular diseases, is known to be associated with atrial fibrillation (AF),
      but its impact on the recurrence of AF after catheter ablation has not been
      explored. METHODS AND RESULTS: The data for 654 consecutive AF patients who
      underwent an index circumferential pulmonary vein ablation were retrospectively
      analyzed. Of them, 323 (49.4%) had MetS according to the modified National
      Cholesterol Education Program-Adult Treatment Panel III criteria and Chinese
      ethnic criteria. After a mean follow-up of 470+/-323 (91-1,245) days, patients
      with MetS had a significantly higher incidence of AF recurrence (43.7%) compared
      with non-MetS patients (30.5%, P<0.001). Univariate analysis revealed that
      nonparoxysmal AF, left atrial size, MetS and body mass index were predictors of
      AF recurrence. Multivariate analysis revealed that MetS (hazard ratio =1.64, 95%
      confidence interval (CI) 1.07-2.49, P=0.022) and nonparoxysmal AF (hazard ratio
      =1.57, 95% CI 1.15-2.14, P=0.004) were independent predictors of AF recurrence.
      The major complications rate did not differ between the MetS and the non-MetS
      groups (1.86% vs 2.42%, P=0.621). CONCLUSIONS: MetS diagnosed prior to AF
      ablation is an independent predictor of AF recurrence.

PMID- 19179775
TI  - Noninvasive characterization of intra-atrial reentrant tachyarrhythmias after
      surgical repair of congenital heart diseases.
AB  - BACKGROUND: Intra-atrial reentrant tachyarrhythmia (IART) after surgical repair
      for congenital heart diseases (CHD) has not been noninvasively characterized.
      METHODS AND RESULTS: The 28 patients after surgery for CHD and 14 patients
      without surgery were investigated by 87-lead body surface mapping (BSM), 12-lead
      electrocardiogram (ECG), 20-lead signal averaged ECG (SAECG) and endocardial
      electroanatomical mapping (CARTO) during clockwise (CW: n=9) or counterclockwise
      (CCW: n=5) incisional atrial tachycardia (Incision-AT), CCW (n=23) or CW (n=4)
      cavotricuspid isthmus-dependent atrial flutter (CTI-AFL), and double-loop reentry
      (n=4). On the BSM, the isopotential map pattern and its locus of the minimum
      potential could differentiate the reentrant circuits, and the activation map
      revealed the reentrant circuits, which were highly coincident with those obtained
      from CARTO. On the 12-lead ECG, negative-positive polarity in the inferior leads
      or a discordant pattern in the precordial leads was observed in all cases of CTI
      AFL, but 3/14 Incision-AT, positive polarity in lead V(1) was observed in all
      cases of CCW, but none of CW CTI-AFL, positive polarity in lead I was observed in
      all cases of CW, but none of CCW Incision-AT. CONCLUSIONS: Flutter-wave
      isopotential map and its activation sequence from the BSM predict reentrant
      circuits of IART after surgery for CHD. Flutter-wave polarity on the 12-lead ECG
      could differentiate these reentrant patterns.

PMID- 19179776
TI  - Pulmonary atresia with ventricular septal defects and major aortopulmonary
      collateral arteries.
AB  - BACKGROUND: There is no consensus on the long-term outcome after unifocalization
      in patients undergoing surgery for pulmonary atresia with ventricular septal
      defects (VSD) and major aortopulmonary collateral arteries (MAPCAs). METHODS AND
      RESULTS: From 1988 to 2006, 40 patients (median age 8.5 months) underwent surgery
      for pulmonary atresia, VSD, and MAPCAs. The hospital mortality rate for the
      preparatory procedures was 1.2%; 17 patients had a complete repair (CR) at a
      median age of 3 years. Patients with a pulmonary artery index greater than 100
      mm(2)/m(2) had a higher likelihood of CR. The overall survival rate 15 years
      after first operation in the CR group was 87.5%. Cox analysis demonstrated that
      increased number of MAPCAs (P=0.019, HR=1.666) was a significant predictor of
      poor survival, and CR (P=0.025, HR=0.141) was a significant predictor of
      favorable prognosis. On angiography, serial measurements of MAPCAs showed a
      significant decrease in size (from 5.2+/-2.9 to 4.1+/-2.9 mm after a mean of 20
      months) (P<0.0001). CONCLUSIONS: Long-term survival into adulthood can be
      achieved with an integrated approach. Late survival depends on the number of
      MAPCAs, and CR. Growth potential of unifocalized MAPCAs was not definite.

PMID- 19179777
TI  - Spontaneous and simultaneous multivessel coronary spasm causing multisite
      myocardial infarction, cardiogenic shock, atrioventricular block, and ventricular
      fibrillation.
AB  - A 57-year-old Taiwanese man with a past history of variant angina developed
      simultaneous anterior and inferior myocardial infarction, atrioventricular block,
      cardiogenic shock, and eventually ventricular fibrillation. Left coronary
      angiography revealed simultaneous occlusion of the left anterior descending and
      the left circumflex coronary arteries, which was relieved by intracoronary
      administration of isosorbide dinitrate. This is the first report of such a case
      in the English-language medical literature.

PMID- 19179778
TI  - Restored cardiac conditions and left ventricular function after parathyroidectomy
      in a hemodialysis patient. Parathyroidectomy improves cardiac fatty acid
      metabolism assessed by 123I-BMIPP.
AB  - A 62 year-old female hemodialysis patient underwent parathyroidectomy to treat
      secondary hyperparathyroidism. On the preoperative assessment, the plasma levels
      of parathyroid hormone (PTH) and B-type natriuretic peptide (BNP) were elevated.
      Echocardiography showed reduced left ventricular (LV) contraction. Myocardial
      iodine-123-15-(p-iodophenyl)-3-(R,S) methylpentadecanoic acid ((123)I-BMIPP)
      scintigraphy showed moderately reduced tracer uptake in the postero-inferior area
      on single-photon emission computed tomography and decreased washout on the planar
      images. After parathyroidectomy, the plasma levels of PTH and BNP decreased,
      followed by improvement in LV contraction. Myocardial (123)I-BMIPP scintigraphy
      revealed that the washout on planar images had increased, which suggests that
      myocardial (123)I-BMIPP scintigraphy is useful for estimating the effect of
      parathyroidectomy on cardiac function.

PMID- 19179779
TI  - Pathological finding of sirolimus-eluting stent (SES) restenosis lesion with
      black hole appearance on intravascular ultrasound.
AB  - Restenosis still occurs, even with the sirolimus-eluting stent (SES), and the
      precise mechanisms have not yet been elucidated. In the present case, focal in
      stent stenosis was discovered on angiography 16 months after SES implantation.
      Intravascular ultrasound revealed an echolucent homogeneous zone, which has been
      termed "black hole". A sample of stenotic tissue retrieved by aspiration revealed
      neointimal hyperplasia, composed of proteoglycans and smooth muscle cells with
      scanty cellularity. Furthermore, infiltration of many macrophages and T
      lymphocytes coexisted in the restenotic tissue. These findings suggest that
      delayed healing is 1 of the mechanisms of SES restenosis.

PMID- 19179780
TI  - Efficacy of oral sildenafil in a beraprost-treated patient with severe pulmonary
      hypertension secondary to type I glycogen storage disease.
AB  - Pulmonary arterial hypertension (PAH) is a rare complication of glycogen storage
      disease (GSD), and several cases with a poor outcome have been reported. A 17
      year-old boy, who was diagnosed with GSD at 1 year of age, complained of
      shortness of breath on exertion, and was diagnosed with PAH based on the
      echocardiographic findings. Beraprost sodium (BPS) was started, and his symptoms
      improved after 3 months of treatment. Eighteen months later, he experienced
      frequent episodes of syncope. Because increasing the dose of BPS was ineffective,
      he was admitted to hospital. The echocardiogram showed marked elevation of the
      right ventricular pressure and low cardiac output, and his symptoms deteriorated
      despite continuous infusion of olprinone hydrochloride. Because a single dose of
      sildenafil increased his cardiac output, treatment with 25 mg sildenafil twice
      daily was started. His symptoms gradually ameliorated, and 3 weeks later he left
      the hospital. Two months after starting sildenafil, the cardiac index and the
      serous B-type natriuretic peptide concentration had become normal. Sildenafil may
      be effective in patients with secondary PAH and in patients who have developed
      tolerance to BPS.

PMID- 19179781
TI  - [First time of gerontology in Japan].

PMID- 19179782
TI  - [History of the Japan Geriatrics Society from 1959 to 2008].

PMID- 19179783
TI  - [What very aged societies expect to the Japan Geriatrics Society: views from the
      standpoint of gerontology].

PMID- 19179784
TI  - [Super aged society and the Japan Geriatrics Society].

PMID- 19179785
TI  - [Therapeutic approach to chronic skin ulcers].

PMID- 19179786
TI  - [Anemia in elderly patients].

PMID- 19179787
TI  - [Japan Atherosclerosis Society guidelines for prevention of atherosclerotic
      diseases in Japanese].

PMID- 19179788
TI  - [Guideline for the management of elderly hypertension].

PMID- 19179790
TI  - [Home care for older adults with terminal disease].

PMID- 19179789
TI  - [Terminal care at home for the elderly].

PMID- 19179791
TI  - [End-of-life care for the older residents living in nursing homes].

PMID- 19179792
TI  - [End of life care at long term care facilities for elderly].

PMID- 19179793
TI  - [Localized cerebral blood flow changes in response to ADL-related vitality in
      elderly patients with dementia using single photon emission computed tomography].
AB  - AIM: To clarify the area in the brain related to responsible for vitality and
      volition. METHODS: We studied 123 outpatients (39 men, 84 women, 77.7+/-6.7 years
      old) who visited the Center for comprehensive care on memory disorders in Kyorin
      University Hospital. No patients were prescribed with anti-depressants, anti
      anxiety agents, psychomimetics, acetylcholinesterase inhibitors, Chinese herbal
      medicines or cerebrovascular circulation modifying drugs. Patients with
      frontotemporal dementia or depression were excluded. ADL-related vitality and
      volition was measured by a vitality index. Cerebral brain blood flow was measured
      by single photon emission computed tomography (99mTc-ECD SPECT). Relative blood
      flow changes were calculated by Statistical Parametric Mapping (SPM). Absolute
      blood flow changes were calculated by a three-dimensional stereotaxic ROI
      template on anatomically standardised 99mTc-ECD SPECT (3D SRT). Statistically
      significant correlations between semi-quantitatively measured scores of vitality
      index and blood flow changes in SPM and 3D-SRT were tested and displayed on a
      brain map. RESULTS: Analysis of relative and absolute blood flow showed that the
      common responsible area in the brain related to vitality was the frontal lobe,
      fronto-cingulate gyrus, temporal lobe, basal ganglia (caudate nucleus) and
      thalamus. Blood flow changes in the orbital gyrus were strongly correlated with
      vitality index specially in the frontal lobe. CONCLUSION: ADL-related vitality is
      affected mainly by the blood flow in the frontal-subcortical circuit. However,
      deep white matter was also important to determine vitality and volition.

PMID- 19179794
TI  - [Preferred and actual place of death among community-dwelling disabled older
      people: findings from a survey of visiting nurses].
AB  - AIM: The purpose of this study was to examine the relationship between preferred
      and actual place of death in community-dwelling disabled older people, based on a
      survey of visiting nurses. METHODS: The present study was a two-year longitudinal
      study. At Time 1, 398 disabled older people were living together with their
      family caregivers. At Time 2 (two years later), the visiting nurses responded to
      a survey for these 398 disabled older people. The relationship between preferred
      and actual place of death of disabled older people was examined. RESULTS: Of
      these disabled older people, 26.4% had died by Time 2. The preferences of the
      place of death of 60% of the disabled older people were not identified by the
      visiting nurses. Approximately 40% of the family caregivers' preferences
      concerning the place of death for their older adults were not identified by the
      visiting nurses. The disabled older adults tended to die at their preferred place
      of death if the visiting nurses had identified the preferences. CONCLUSION: In
      order to assist disabled older people to die at their preferred place of death,
      visiting nurses should identify the preferences of disabled older people or their
      family concerning the place of death of the disabled older people.

PMID- 19179795
TI  - [The influence of wearing a diaper on static and dynamic postural control in the
      elderly].
AB  - AIM: To clarify characteristics of static and dynamic postural control in elderly
      people, postural sway during static standing, during an activity, and static
      standing after the activity were compared between young and elderly subjects. In
      this study, the action of raising pants-type diapers was selected as the model
      activity for the measurement of dynamic postural control ability. METHODS: To
      make differences in the ease of putting on the diapers, their contraction
      strength around the abdomen was adjusted at 5 levels from loose to tight.
      Postural sway was measured first during static standing with open and closed eyes
      and, then, during activity and static standing after activity. The subjects'
      perceived difficulty in putting on the diapers was also evaluated. RESULTS:
      Postural sway tended to be larger in elderly than younger subjects during static
      standing, but the differences were not significant. Also, postural sway was
      markedly increased in elderly subjects during the raising of diapers requiring
      greater effort. In static standing after an action, postural sway also remained
      increased after putting on diapers requiring greater effort only in the elderly
      group. CONCLUSIONS: Postural sway increased, indicating a decline in the dynamic
      postural control ability, during an action in association with its level of
      difficulty even in elderly people showing no decline in static postural control
      ability. In addition, dynamic postural control responses appeared to affect
      subsequent static postural control responses, inducing a decline in ability.

PMID- 19179796
TI  - [Epidemiological study on atrial fibrillation among aged members of a Japanese
      community].
AB  - AIM: Epidemiological studies on atrial fibrillation (AF) in Japanese is scarce.
      As aging is one of the contributing factors to AF, we investigated the prevalence
      of AF among aged members of a Japanese community. METHODS: Samples were community
      residents who were aged 65 years or older from town I, which is located at the
      north end of Kyoto Prefecture, Japan, and 39.9% of the population is over age 65
      years old. For a period of 22 months starting in March, 2006, three groups of
      residents were evaluated: out-patients of the community clinic (the patients
      group); those who participated in annual residents' check up including ECG (the
      check-up group) and residents who visited clinics for influenza vaccinations (the
      pulse-examination group). RESULTS: This study screened 550 patients (81.2% of
      residents more than 65 years old) in the jurisdiction of the town clinic. A total
      of 44 residents were diagnosed as having AF, that is 8.0% of residents screened
      over 65 years old in town. This resulted in a prevalence of 6.5% among all
      residents over 65 years old. Patient's age ranged from 65 to 94 years old. The
      male to female ratio was 0.58: 1 and chronic AF was 52.3%. There were 42 subjects
      with AF out of 419 in the patients group, 2 subjects with AF out of 97 in the
      check-up group, and no subjects with AF in the pulse-examination group. Among the
      42 subjects with AF in the patients group, 88.1% had non-valvular AF and 71.4%
      had hypertension. Eight patients (19%) suffered from brain infarction and
      transient ischemic attack, and ten had non-symptomatic AF (23.8%). Among this
      group, 37.8% had a CHADS2 score above 3. Twenty-three patients (54.8%) received
      anti-coagulation medication and 15 (35.7%) received anti-arrhythmic medication.
      CONCLUSION: The prevalence of atrial fibrillation among elderly patients in a
      community in Japan was 8.0%. This group has a high risk of brain infarction. As
      nearly 24% of patients had non-symptomatic AF, it is important to keep non
      symptomatic AF in mind in the treatment of the elderly in order to improve their
      ADL and QOL.

PMID- 19179797
TI  - [Advance care planning among the general public in Japan: association with
      awareness about dementia].
AB  - AIM: To explore attitudes towards advance care planning among the general public
      in Japan and to examine the association between the advance care planning and
      awareness about dementia. METHODS: We conducted a postal self-administered
      questionnaire survey in a sample of the general population aged 40 and over and
      86% (n=2,161) of the sample were eligible for analysis. The question items
      included sociodemographic characteristics, awareness about dementia (anxiety
      about dementia and knowledge about dementia), and advance care planning (decision
      making on own care preference if extra assistance were required and disclosure of
      their care preferences to family members). RESULTS: More than a half of the
      participants had yet to consider what kind of care they preferred to receive if
      extra assistance were required, especially in men and younger people. Although
      some people had made a decision regarding care preferences, only 39% of those had
      disclosed their wishes for care to family members. People who had higher
      awareness (anxiety and knowledge) about dementia were more likely to consider or
      make a decision about care preferences, irrespective of age and gender. On the
      other hand, the disclosure of care preferences to family members was associated
      with the age groups but not with the extent of awareness about dementia.
      CONCLUSIONS: The general public in Japan are not used to determining and
      disclosing their own preferences on advance care planning. There is clearly a
      need for greater public awareness and further study about an effective method for
      enhancement of advance care planning.

PMID- 19179798
TI  - [A cross-sectional study on the relationship between the Trail Making Test and
      mobility-related functions in community-dwelling elderly].
AB  - AIM: The Trail Making Test (TMT) has been studied in western countries as an
      indicator of executive function, but there are few data on the TMT in Japan. This
      study was conducted to assess the characteristics of TMT and to explore the
      effect of TMT on physical function among community-dwelling elderly Japanese to
      promote health in the aged. METHODS: Subjects were 175 individuals aged>or=65
      years (57 men and 118 women). The TMT test which consists of two parts (part A
      and part B)was performed. 8 physical function items such as indicators of
      functional decline (usual walking speed, timed up-and-go (TUG), one-leg standing
      balance, and handgrip strength), and indicators of mobility (maximum walking
      speed, TUG with cup, stair-climbing, obstacle-negotiating gait) were measured.
      For this analysis, we used a difference score defined as TMT calculated as the
      difference between times (part B-part A=TMT). Data were analyzed by sex
      respectively. RESULTS: The median TMT value was 58.61 seconds in men and 65.67
      seconds in women. TMT value increased with age and there was no difference
      between men and women in absolute values. multinomial logistic regression
      analysis showed that poor TMT was related to low tertiles of TUG, handgrip
      strength, MWS, TUG with cup, stair-climbing and obstacle-negotiating gait, and to
      intermediate tertile of MWS with adjustment for age and sex. CONCLUSION: TMT was
      significantly associated with mobility-related functions, suggesting that TMT, as
      the indicator of executive function, should be considered to be included in the
      test batteries for evaluating older people.

PMID- 19179799
TI  - [The implementation of personalized treatment for osteoporosis].
AB  - AIM: To establish personalized treatment of osteoporosis. METHODS: A T869-->C
      polymorphism in exon 1 of the transforming growth factor-beta1 gene, which
      results in a Leu-->Pro substitution at amino acid 10, is reported to be
      associated with the rate of bone loss as well as the response to active vitamin D
      treatment. Therefore, we determined this single nucleotide polymorphism (SNP) to
      estimate the need of active vitamin D treatment. We also determined serum level
      of 25 hydroxy-vitamin D to evaluate a degree of vitamin D fulfillment. Based on
      these data, we categorized postmenopausal patients into four groups; C homozygote
      with vitamin D deficiency patients to whom 1 microg/day active vitamin D was
      administered, C homozygote without vitamin D deficiency patients or those who
      bore at least one T-allele with vitamin D deficiency to whom 0.5 microg/day
      active vitamin D was administered, and patients who bore at least one T-allele
      without vitamin D deficiency to whom no drug was given. The patients were checked
      up every 6 months with regard to changes in bone mineral density and occurrence
      of fresh fractures. RESULTS: The SNP was associated with prevalent vertebral
      fractures; the frequency of the T allele was significantly greater in patients
      with vertebral fractures. Furthermore, the serum level of 25 hydroxy-vitamin D
      was significantly lower in patients with vertebral fractures, which were observed
      in 17 out of 34 patients who bore at least one T-allele as well as vitamin D
      deficiency, while only 2 of 15 homozygous C-allele carriers without vitamin D
      deficiency suffered from fractures. CONCLUSION: These findings suggest that the
      SNP in combination with the serum level of 25 hydroxy-vitamin D can predict
      fracture risk in postmenopausal osteoporosis.

PMID- 19179800
TI  - [A case of nasal NK/T cell lymphoma presenting with bilateral giant adrenal
      tumors].
AB  - A 76-year-old woman presented to a clinic with fever and loss of body weight.
      Abdominal echogram showed bilateral adrenal swelling (left adrenal 90x80 mm,
      right adrenal 50x20 mm) and she was admitted to the hospital for further
      examination. A tumor was also found inside nasal cavity by enhanced computed
      tomography (CT), and abnormal uptake in the nasal cavity and adrenal gland was
      shown in gallium scintigraphy. Laboratory tests revealed the elevation of lactate
      dehydrogenase (LDH) and sIL-2R. Biopsy of the nasal tumor revealed nasal natural
      killer or thymus-derived (NK/T) cell lymphoma. No Epstein-Barr virus (EBV) 
      encoded RNA was detected in tissue. After THP-COP chemotherapy regimen, both the
      nasal and adrenal tumors decreased in size. However, a CT scan taken on admission
      revealed a pulmonary embolism. After treatment with heparin and warfarin, emboli
      disappeared. Chemotherapy was continued, but perforation of the small intestine
      occurred. Since the prognosis was poor, no operation was performed. Her condition
      slowly, and she died 60 days after admission. Since she had a high level of
      plasma ACTH (158.0 pg/ml) and normal serum cortisol (14.6 microg/dl), partial
      adrenal insufficiency was suspected. In addition, since her cortisol circadian
      rhythm was lost and cortisol levels were not completely suppressed by the 1 mg
      and 8 mg dexamethasone test, she met the criteria of the diagnosis of preclinical
      Cushing syndrome. NK/T cell lymphoma with giant adrenal tumor is extremely rare,
      but should be considered as one of the differential diagnoses of bilateral
      adrenal tumor.

PMID- 19179801
TI  - The dose-response relationship between pulmonary function injury and cumulative
      dose of tobacco dust exposure among tobacco processing workers.

PMID- 19179802
TI  - Job stress and coronary heart disease: a case-control study using a Chinese
      population.
AB  - OBJECTIVES: This study was to examine the association between job stress and
      coronary heart disease (CHD) in a Chinese population. METHODS: The 388
      participants aged 30 to 70 yr who received coronary angiography for suspected or
      known ischemic heart disease were enrolled in this series, which included 292 CHD
      cases and 96 controls. The job stress before CHD onset was measured by the effort
      reward imbalance (ERI) model. RESULTS: In the results, compared with the
      baseline, high ERI, high extrinsic effort or high overcommitment increased the
      risk of CHD with odds ratios (OR) of 2.8, 2.7 and 2.8 respectively after
      adjustment for the traditional CHD risk factors, such as age, gender, primary
      hypertension, diabetes mellitus, hyperlipidemia, smoking, body mass index, CHD
      family history, educational level, and marital status. The combination of high
      ERI and high overcommitment led to the highest risk of CHD with adjusted OR 5.5.
      However, high reward reduced the risk of CHD with an adjusted OR of 0.4 in
      comparison to low reward. Dose-response relationships were also observed.
      CONCLUSIONS: Job stress evaluated by the ERI model significantly increased the
      risk of CHD, and it may be an important risk factor independent of the
      traditional risk factors of CHD in the Chinese population.

PMID- 19179803
TI  - Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)
      mediated signal transduction pathway: role of GSK-3beta in adult brain.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is a constitutively active kinase.
      Since its activation results in neurofibrillary tangle (NFT) deposits in aged and
      Alzheimer's disease (AD) brains, GSK-3beta may be inhibited under normal
      conditions but activated under pathological conditions. Given its link to NFT
      formation, we sought to determine whether GSK-3beta exists in the brain as a
      "pathological time bomb" that promotes disease development. To address this
      hypothesis, we analyzed GSK-3beta heterozygote (GSK+/-) mice, which express GSK
      3beta at 50% wild-type levels. When tested in the Morris water maze test, GSK+/-
      mice surprisingly exhibited retrograde amnesia. Further analysis indicated that
      GSK+/- mice had impaired memory reconsolidation but normal memory consolidation.
      Therefore, we concluded that GSK-3beta activation is required for memory
      reconsolidation in the adult brain.

PMID- 19179804
TI  - Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)
      mediated signal transduction pathway: inhibitors of the Wnt/beta-catenin
      signaling pathway as novel anticancer drugs.
AB  - Accumulating evidence suggests that the Wnt/beta-catenin signaling pathway is
      often involved in oncogenesis and cancer development. Accordingly, a novel
      anticancer drug can be developed using inhibitors of this pathway. However, at
      present, there is no selective inhibitor of this pathway available as a
      therapeutic agent. Although all the components of the Wnt/beta-catenin signaling
      pathway can be a target for drug development, glycogen synthase kinase-3beta (GSK
      3beta), in particular, may be a good target because GSK-3beta is an essential
      component of the pathway, and activation of this kinase results in the inhibition
      of the Wnt signaling pathway. We found that the differentiation-inducing factors
      (DIFs), putative morphogens for Dictyostelium discoideum, inhibit the Wnt/beta
      catenin signaling pathway via the activation of GSK-3beta, resulting in the cell
      cycle arrest of human cancer cell lines. In this review, we summarize our recent
      findings on the antiproliferative effect of DIFs and show the possibility for
      development of a novel anticancer drug from DIFs and their derivatives.

PMID- 19179805
TI  - Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)
      mediated signal transduction pathway: role of GSK-3beta in myocardial protection
      against ischemia/reperfusion injury.
AB  - Although reperfusion is required to salvage ischemic myocardium from necrosis,
      reperfusion per se induces myocardial necrosis. In this "lethal reperfusion
      injury", opening of the mitochondrial permeability transition pore (mPTP) upon
      reperfusion is crucially involved. The mPTP primarily consists of adenine
      nucleotide translocator (ANT) and voltage-dependent anion channel, and its
      opening is triggered by binding of cyclophilin-D (CyP-D) to ANT, which increases
      Ca(2+) sensitivity of the mPTP. Recent studies have shown that inactivation of
      glycogen synthase kinase-3beta (GSK-3beta) suppresses mPTP opening and protects
      cardiomyocytes. Multiple intracellular signals relevant to cardiomyocyte
      protection converge to GSK-3beta and inactivate this kinase by phosphorylation.
      Although the effect of GSK-3beta phosphorylation on mPTP structure and function
      remains unclear, suppression of ANT-CyP-D interaction by binding of phospho-GSK
      3beta to ANT and reduction in GSK-3beta-mediated phosphorylation of p53 may
      contribute to elevation of the threshold for mPTP opening. Furthermore, a
      significant inverse correlation was observed between level of phospho-GSK-3beta
      at the time of reperfusion and the extent of myocardium infarction in heart.
      Together with the infarct size-limiting effect of GSK-3beta inhibitors, this
      finding indicates that phospho-GSK-3beta is a determinant of myocardial tolerance
      against reperfusion-induced necrosis. Thus, GSK-3beta appears to be a target of
      novel therapy for cardioprotection upon reperfusion.

PMID- 19179806
TI  - Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)
      mediated signal transduction pathway: the role of GSK-3beta in the maintenance of
      steady-state levels of insulin receptor signaling molecules and Na(v)1.7 sodium
      channel in adrenal chromaffin cells.
AB  - Glycogen synthase kinase-3 (GSK-3) is constitutively active in nonstimulated
      cells, where the majority of its substrates undergo inactivation/proteolysis by
      phosphorylation. Extracellular stimuli (e.g., insulin) catalyze inhibitory Ser(9)
      phosphorylation of GSK-3beta, turning on signaling and causing other biological
      consequences otherwise constitutively suppressed by GSK-3beta. Regulated and
      dysregulated activities of GSK-3beta are pivotal to health, disease, and
      therapeutics (e.g., insulin resistance, neurodegeneration, tumorigenesis,
      inflammation); however, the underlying mechanisms of multifunctional GSK-3beta
      remain elusive. In cultured bovine adrenal chromaffin cells, 1) constitutive and
      negatively-regulated activities of GSK-3beta up- and down-regulated insulin
      receptor, insulin receptor substrate-1 (IRS-1), IRS-2, and Akt levels via
      controlling proteasomal degradation and protein synthesis; 2) nicotinic
      receptor/protein kinase C-alpha (PKC-alpha)/extracellular signal-regulated kinase
      (ERK) pathway up-regulated IRS-1 and IRS-2 levels, enhancing insulin-induced the
      phosphoinositide 3-kinase (PI3K)/Akt/GSK-3beta pathway; 3) inhibition of
      calcineurin by cyclosporin A or FK506 down-regulated IRS-2 level, attenuating
      insulin-like growth factor-I (IGF-I)-induced ERK and GSK-3beta pathways; and 4)
      insulin, IGF-I or therapeutics (e.g., lithium) up-regulated the voltage-dependent
      Na(v)1.7 sodium channel.

PMID- 19179807
TI  - Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)
      mediated signal transduction pathway: targeting the Wnt pathway and
      transplantation therapy as strategies for retinal repair.
AB  - Recent advances in stem cell biology have provided new insights that may lead to
      the development of regeneration therapy in the central nervous system to
      replenish lost neurons and to reconstitute neural circuits. The strategies for
      regeneration can be classified into two approaches: i) activation of endogenous
      neural stem cells and ii) transplantation of donor cells to replace lost cells.
      In the adult mammalian retina, Muller glia generate new retinal neurons in
      response to injury. The proliferation and differentiation of Muller glia-derived
      progenitors can be controlled by both intrinsic and extrinsic factors. Members of
      the Wnt/beta-catenin signaling pathway, such as Wnt receptors and glycogen
      synthase kinase-3beta, may be promising drug targets for neural regeneration. On
      the other hand, transplantation of photoreceptors or retinal pigment epithelia
      derived from human embryonic stem cells or induced pluripotent stem cells is also
      promising. Directed differentiation of pluripotent cells into retinal cells and
      purification to obtain retinal cells at a specific ontogenetic stage are required
      for donor cell preparation. Modulation of the host retinal environment to reduce
      the glial barrier is also critical for transplantation. To restore visual
      function, we need to understand the mechanisms underlying the integration of
      newly generated neurons or transplanted cells into the existing neural networks.

PMID- 19179808
TI  - The protective effect of a newly developed molecular chaperone-inducer against
      mouse ischemic acute kidney injury.
AB  - Activation of the unfolded protein response (UPR) has been suggested to attenuate
      renal ischemia-reperfusion (I/R) injury. We recently found a compound, namely
      BIX, that activated the UPR selectively through the activating transcription
      factor 6 pathway. This study examined the effect of BIX on renal I/R injury in
      mice. BIX selectively up-regulated renal BiP mRNA and protein. Pretreatment with
      BIX significantly ameliorated renal I/R injury. Co-administration of BIX and
      tunicamycin, a non-selective UPR inducer, provided no additional protection. Our
      results suggest that the UPR activation by BIX leads to a novel drug therapy
      against renal I/R injury.

PMID- 19179809
TI  - The diagnosis and treatment of hypertensive crises.
AB  - Hypertension (HTN) is one of the most common chronic medical conditions,
      affecting nearly 72 million people in the United States. A systolic blood
      pressure (BP) > 180 mm Hg or a diastolic BP > 120 mm Hg is considered a
      "hypertensive crisis." Hypertensive crises are categorized as either hypertensive
      emergencies or urgencies depending on the degree of BP elevation and presence of
      end-organ damage. The primary goal of intervention in a hypertensive crisis is to
      safely reduce BP. Immediate reduction in BP is required only in patients with
      acute end-organ damage (ie, hypertensive emergency). This requires treatment with
      a titratable shortacting intravenous (IV) antihypertensive agent, while severe
      HTN with no acute end-organ damage (ie, hypertensive urgency) is usually treated
      with oral antihypertensive agents. Patients with hypertensive emergencies are
      best treated in an intensive care unit (ICU) with titratable IV hypotensive
      agents. Rapid-acting IV antihypertensive agents are available, including
      clevidipine, labetalol, esmolol, fenoldopam, nicardipine, and sodium
      nitroprusside. Newer agents such as clevidipine have considerable advantages
      compared with other available agents in the management of hypertensive crises.
      Sodium nitroprusside is an extremely toxic drug, and its use in the treatment of
      hypertensive emergencies should be avoided. Likewise, nifedipine, nitroglycerin,
      and hydralazine should not to be considered first-line therapies in the
      management of hypertensive crises because these agents are associated with
      significant toxicities and/or side effects.

PMID- 19179810
TI  - Are tolerability concerns a class effect of beta-blockers in treating patients
      with hypertension?
AB  - Beta-blockers (beta-blockers) have demonstrated their value across the
      cardiovascular disease spectrum. Beta-blockers effectively lower blood pressure
      in patients with hypertension and provide symptomatic or mortality benefits in
      patients with heart failure and in post-myocardial infarction patients. However,
      despite their utility, beta-blockers remain underused. There have been recent
      concerns that beta-blockers as a class are not as effective as once thought in
      uncomplicated hypertension due to a relatively weak effect on reduction of stroke
      and the absence of an effect on coronary heart disease when compared with placebo
      or no treatment. Underuse can, in part, be related to tolerability concerns. Beta
      blockers have been traditionally associated with side effects including
      depression, fatigue, sexual dysfunction, and cold extremities, which limit their
      acceptance by patients and physicians and may lead to discontinuation of therapy.
      Because of inherent heterogeneity of the beta-blocker class in terms of
      adrenergic receptor selectivity, intrinsic sympathomimetic activity, and
      vasodilatory activity, these agents vary in tolerability profile. Recently, more
      attention has been focused on the third-generation vasodilatory beta-blockers
      (ie, carvedilol, labetalol, and nebivolol), with the recognition that these
      agents may diverge in meaningful ways from the traditional beta-blockers. By
      examining the differences among members of the beta-blocker class, it may be
      possible to determine whether and which tolerability issues are indeed a class
      effect of beta-blockers or whether these agents should be evaluated on a case-by
      case basis.

PMID- 19179811
TI  - Appropriate secondary prevention of acute atherothrombotic events and strategies
      to improve guideline adherence.
AB  - The use of guideline-recommended secondary prevention measures is essential for
      reducing the risk of subsequent events and mortality in patients who have
      survived an acute atherothrombotic event or have peripheral arterial disease.
      Although initial hospitalization provides an ideal environment to initiate such
      therapies, implementation of effective longterm prevention strategies is hindered
      by the absence of a systematic approach. In general, evidence-based clinical
      practice guidelines recommend antiplatelet therapy as a cornerstone of post
      discharge secondary prevention, in addition to preventive measures targeting risk
      factors such as hypertension, dyslipidemia, cigarette smoking, and physical
      inactivity. Observational data indicate that, although there has been improvement
      over time, current utilization of guideline-recommended post-discharge treatment
      remains suboptimal. Recognizing the importance of a systematic approach to
      discharge planning, numerous hospital-based initiatives have been established. In
      conjunction with effective lines of communication between hospital and primary
      care teams, initiation of the most effective secondary prevention strategy at the
      time of hospital discharge will help to ensure optimal long-term management of
      patients after an atherothrombotic event.

PMID- 19179812
TI  - Overview of the gliptin class (dipeptidyl peptidase-4 inhibitors) in clinical
      practice.
AB  - Dipeptidyl peptidase-4 inhibitors (DPP-4s), also commonly called gliptins, are a
      relatively new class of drugs for the treatment of type 2 diabetes. These agents
      work in a unique way to improve insulin secretion from the Beta-cells of the
      pancreas in response to an increase in blood sugar and simultaneously decrease
      glucagon output from the a-cells of the pancreas, which results in decreased
      hepatic glucose output. Specifi cally, gliptins decrease the breakdown of
      glucagon-like peptide-1 (GLP-1) such that the circulating levels reach the high
      normal physiologic GLP-1 range. This results in more prompt and appropriate
      secretion of insulin and suppression of glucagon in response to a carbohydrate
      containing meal or snack. The change in glucagon correlates linearly with
      improvement in glucose tolerance. Since these drugs improve insulin secretion in
      response to an increase in blood glucose, it seems appropriate to pair them with
      drugs that have a different mechanism of action, such as insulin sensitizers or
      metformin. In fact, improvements in fasting and postprandial glucose levels,
      improved beta-cell function, and improvement in HbA1c levels have been
      demonstrated in numerous clinical trials using different gliptins as monotherapy
      and in combination with various type 2 diabetes medications, including insulin.
      This article reviews data from a number of clinical trials, presentations, and
      abstracts indicating the importance of the DPP-4 inhibitors sitagliptin,
      vildagliptin, and alogliptin both alone and in combination with insulin
      sensitizers in the treatment of type 2 diabetes.

PMID- 19179813
TI  - Impact of incretin therapy on islet dysfunction: an underlying defect in the
      pathophysiology of type 2 diabetes.
AB  - Glucose homeostasis is governed by a complex interplay of hormonal signaling and
      modulation. Insulin, glucagon, amylin, the incretin hormones glucose-dependent
      insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and other
      hormones and enzymes interact to maintain glucose homeostasis and normal cellular
      metabolism. Derangements in these hormonal interactions, particularly insulin
      deficits and impaired insulin action, result in the development of type 2
      diabetes-but only in individuals who have experienced significant dysfunction or
      loss of beta-cells, located in the pancreatic islets of Langerhans. Much less is
      known about the impact of alpha-cell dysregulation on glucose homeostasis,
      although it has been demonstrated that glucagon-secreting alpha-cells, also
      located in the pancreatic islets, play an important role in glucose metabolism.
      Because beta-cell dysfunction occurs early in the course of type 2 diabetes and
      is progressive, early intervention with therapies that improve beta-cell function
      is desirable. In addition to reducing HbA1c and fasting plasma glucose, the
      recently developed diabetes therapies GLP-1 receptor agonists (eg, exenatide,
      liraglutide) and dipeptidyl peptidase-4 (DPP-4) inhibitors (eg, sitagliptin,
      vildagliptin) appear to have beneficial effects on beta-cell dysfunction and,
      possibly, on alpha-cell dysregulation.

PMID- 19179814
TI  - The potential role of prasugrel in secondary prevention of ischemic events in
      patients with acute coronary syndromes.
AB  - Acute coronary syndromes (ACS) are life-threatening manifestations of coronary
      artery disease, occurring when a thrombus forms at the site of atherosclerotic
      plaque rupture or fissuring. Almost all patients discharged from the hospital
      after an ACS (myocardial infarction or unstable angina) in the United States
      receive antiplatelet therapy. Current recommendations for post-ACS antiplatelet
      therapy are aspirin 75 to 162 mg/day indefinitely for all patients, plus a
      thienopyridine (currently clopidogrel 75 mg/day) for > or = 12 months in those
      receiving stents unless there is a high risk of bleeding. Dual antiplatelet
      therapy is indicated because patients with ACS have a hypercoagulable state which
      persists for at least 6 months after the acute event, and agents targeting
      different mechanisms have synergistic antiplatelet effects. The thienopyridine
      class includes ticlopidine, clopidogrel, and prasugrel. Clopidogrel is
      recommended in guidelines because ticlopidine carries a higher risk of adverse
      events including blood dyscrasias. Prasugrel is not yet available outside of a
      research setting. Clopidogrel + aspirin reduces the risk of an adverse clinical
      event after ACS by 15% and after percutaneous coronary intervention (PCI) by 34%.
      However, there is considerable interpatient variability in response to
      clopidogrel and a mean of 21% of patients (95% confidence interval [CI], 17 % -
      25%) are nonresponsive to the drug as measured by platelet aggregation
      inhibition. Nonresponsiveness is associated with an increased risk of secondary
      ischemic events. Compared with clopidogrel, the newest thienopyridine, prasugrel,
      has a faster onset of platelet inhibition and less variability of response. In
      clinical trials, the combination of prasugrel + aspirin reduced the risk of a
      second ischemic event by 19% compared with clopidogrel + aspirin. There is a
      small increase in the risk of bleeding with dual antiplatelet therapy, but the
      benefit still outweighs the risk in most patients. Patients with a history of
      transient ischemic attack or stroke should not receive prasugrel + aspirin
      because of increased risk of events.

PMID- 19179815
TI  - The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol,
      and progesterone) safer or more efficacious than commonly used synthetic versions
      in hormone replacement therapy?
AB  - BACKGROUND: The use of bioidentical hormones, including progesterone, estradiol,
      and estriol, in hormone replacement therapy (HRT) has sparked intense debate. Of
      special concern is their relative safety compared with traditional synthetic and
      animal-derived versions, such as conjugated equine estrogens (CEE),
      medroxyprogesterone acetate (MPA), and other synthetic progestins. Proponents for
      bioidentical hormones claim that they are safer than comparable synthetic and
      nonhuman versions of HRT. Yet according to the US Food and Drug Administration
      and The Endocrine Society, there is little or no evidence to support claims that
      bioidentical hormones are safer or more effective. OBJECTIVE: This paper aimed to
      evaluate the evidence comparing bioidentical hormones, including progesterone,
      estradiol, and estriol, with the commonly used nonbioidentical versions of HRT
      for clinical efficacy, physiologic actions on breast tissue, and risks for breast
      cancer and cardiovascular disease. METHODS: Published papers were identified from
      PubMed/MEDLINE, Google Scholar, and Cochrane databases, which included keywords
      associated with bioidentical hormones, synthetic hormones, and HRT. Papers that
      compared the effects of bioidentical and synthetic hormones, including clinical
      outcomes and in vitro results, were selected. RESULTS: Patients report greater
      satisfaction with HRTs that contain progesterone compared with those that contain
      a synthetic progestin. Bioidentical hormones have some distinctly different,
      potentially opposite, physiological effects compared with their synthetic
      counterparts, which have different chemical structures. Both physiological and
      clinical data have indicated that progesterone is associated with a diminished
      risk for breast cancer, compared with the increased risk associated with
      synthetic progestins. Estriol has some unique physiological effects, which
      differentiate it from estradiol, estrone, and CEE. Estriol would be expected to
      carry less risk for breast cancer, although no randomized controlled trials have
      been documented. Synthetic progestins have a variety of negative cardiovascular
      effects, which may be avoided with progesterone. CONCLUSION: Physiological data
      and clinical outcomes demonstrate that bioidentical hormones are associated with
      lower risks, including the risk of breast cancer and cardiovascular disease, and
      are more efficacious than their synthetic and animal-derived counterparts. Until
      evidence is found to the contrary, bioidentical hormones remain the preferred
      method of HRT. Further randomized controlled trials are needed to delineate these
      differences more clearly.

PMID- 19179816
TI  - Clinical and societal consequences of obstructive sleep apnea and excessive
      daytime sleepiness.
AB  - Obstructive sleep apnea (OSA) is the most common sleep-related breathing
      disorder. Although frequently undiagnosed, OSA is highly prevalent and presents
      most often with excessive daytime sleepiness (EDS). While obesity is the major
      predisposing factor, patients with OSA and EDS are at increased risk of other
      conditions, including cardiovascular disease, type 2 diabetes, cognitive
      impairment, and depression. Significant consequences include morbidity and
      mortality from the associated conditions in addition to personal and societal
      consequences of cognitive impairment, such as driving and workplace accidents.
      Primary care physicians are ideally placed to screen for OSA and EDS in patients
      who present with commonly comorbid conditions such as obesity, cardiovascular
      disease, metabolic syndrome, and depression. Conversely, treatment of OSA and
      associated EDS might help alleviate significant comorbidities and their clinical
      and societal consequences.

PMID- 19179817
TI  - The renoprotective effects of RAS inhibition: focus on prevention and treatment
      of chronic kidney disease.
AB  - Chronic kidney disease (CKD) shares major risk factors with cardiovascular
      disease(CVD), including hypertension and diabetes mellitus. In patients with
      hypertensive kidney disease and diabetic nephropathy, inhibitors of the renin
      angiotensin system (RAS) significantly reduce the risk of renal and
      cardiovascular endpoints. Whether the renoprotective effects of RAS inhibitors
      can be fully accounted for by blood pressure reductions or whether other
      mechanisms are involved has not been clearly established. Because RAS inhibitors
      reduce albuminuria and slow progression of kidney disease, they are recommended
      as fi rst-line antihypertensive agents in patients with CKD, who often require
      aggressive treatment with > or = 2 drugs to reach the goal blood pressure (<
      130/80 mm Hg). Greater RAS inhibition with higher-than-usual doses of a single
      agent or dual RAS inhibition with an angiotensin-converting enzyme inhibitor and
      an angiotensin receptor blocker may be necessary for maximum renoprotective
      effects. Ongoing clinical trials assessing treatment and prevention of CKD may
      resolve unanswered questions about RAS inhibition in patients with hypertension
      and/or diabetes.

PMID- 19179818
TI  - Managing stable COPD in 2009: incorporating results from recent clinical studies
      into a goal-directed approach for clinicians.
AB  - Chronic obstructive pulmonary disease (COPD) is prevalent in primary care
      practice and an important cause of functional decline, hospitalizations, and
      death. Recent clinical trials of COPD therapy demonstrate the ability of
      bronchodilators (especially long-acting beta2-agonists and anticholinergics),
      either alone or in combination with inhaled corticosteroids, to achieve the goals
      of managing stable disease. These management goals include: symptom relief,
      improvement in exercise tolerance and health status, prevention of exacerbations
      and progression of disease, and reduction in mortality. Recent studies of COPD
      treatment also provide important safety information to help clinicians address
      patient concerns about treatment risks. We reviewed recent clinical trials to
      develop concepts of care for the non-specialist clinician managing patients with
      stable COPD.

PMID- 19179819
TI  - The management of hypogonadism in aging male patients.
AB  - This article focuses on the evaluation and management of hypogonadism in aging
      male patients in the light of recent guidelines. The benefits of treating severe
      hypogonadism resulting from identifiable pituitary or primary gonadal disease are
      well established. Milder forms of hypogonadism in the aging male, known as
      andropause, are common, and constitute an expanding area of clinical interest and
      research. Several studies indicate that testosterone replacement therapy may
      produce a wide range of benefits for men with hypogonadism, including improvement
      in libido, bone density, muscle mass, body composition, mood, and cognition.
      Currently available data are insufficient to permit a definitive verdict on the
      balance between risks and benefits of testosterone replacement therapy in aging
      males.

PMID- 19179820
TI  - Diagnosis and management of nasal congestion: the role of intranasal
      corticosteroids.
AB  - Nasal congestion is considered the most bothersome of allergic rhinitis (AR)
      symptoms and can significantly impair ability to function at work, home, and
      school. Effective management of AR-related nasal congestion depends on accurate
      diagnosis and appropriate treatment. Many individuals with AR and AR-related
      congestion remain undiagnosed and do not receive prescription medication.
      However, new tools intended to improve the diagnosis of nasal congestion have
      been developed and validated. Intranasal corticosteroids (INSs) are recommended
      as first-line therapy for patients with moderate-to-severe AR and also when nasal
      congestion is a prominent symptom. Double blind, randomized clinical trials have
      demonstrated greater efficacy of INSs versus placebo, antihistamines, or
      montelukast for relief of all nasal symptoms, especially congestion. Patient
      adherence to treatment also affects outcomes, and this may be influenced by
      patient preferences for the sensory attributes of an individual drug. Increased
      awareness of the effects of AR-related nasal congestion, the efficacy and safety
      of available pharmacotherapies, and barriers to adherence may improve clinical
      outcomes.

PMID- 19179821
TI  - Are screening guidelines for abdominal aortic aneurysms being implemented within
      a large VA primary health care system?
AB  - BACKGROUND: Screening men aged 65 to 75 years who have ever smoked for abdominal
      aortic aneurysm (AAA) has been recommended to reduce AAA-related mortality.
      However, it is unknown whether the evidence-based recommendation has been
      implemented within primary care. OBJECTIVE: The aim of this study was to
      determine whether screening for AAA is being performed within a large Veterans
      Affairs (VA) primary health care system. METHODS: This was a retrospective cohort
      study examining AAA screening practices within the VA Connecticut Healthcare
      System. Any of the following imaging procedures were considered screening tests
      for AAA: abdominal ultrasound, computed tomography (CT) of the abdomen, CT
      colography, or magnetic resonance imaging of the abdomen. RESULTS: A total of 279
      patients were included in the cohort: 83 (30%) were offered screening for AAA or
      had recent imaging performed that would have allowed for detection of an AAA.
      Seventy-three patients (26%) underwent AAA screening or had recent imaging of
      their abdomens, while 10 patients either refused imaging or were awaiting
      ultrasonographic screening at the time of this study. Of the 73 patients who had
      undergone screening or other abdominal imaging evaluations, 9 (12.3%) were found
      to have AAAs. CONCLUSIONS: There appears to be a low rate of screening for AAA
      within 1 primary care setting in a large VA health care system. If this finding
      is replicated within other VA primary health care settings, then the VA health
      care system should consider implementing a performance metric within primary care
      to improve AAA screening rates.

PMID- 19179822
TI  - Current trends in age-related macular degeneration.
AB  - Age-related macular degeneration is the leading cause of irreversible blindness
      in older persons of the developed world. Addressing treatable risk factors
      reduces the incidence and progression of this condition. Recent advances in
      understanding and treating macular degeneration have dramatically improved the
      visual prognosis.

PMID- 19179823
TI  - An update on acute and chronic urticaria for the primary care provider.
AB  - Urticaria is a common dermatologic condition seen by primary care physicians.
      Urticaria can result in significant morbidity and a dramatic decline in quality
      of life. Acute urticaria is mostly an allergic or IgE-mediated reaction and tends
      to be self-limited, while chronic urticaria generally does not exhibit any
      specific external cause and is therefore considered idiopathic. Evidence suggests
      that up to 30% to 50% of idiopathic cases may be autoimmune and/or related to
      mast cell/basophil abnormalities. There is further evidence of an autoantibody to
      the high-affinity receptor for IgE (FcepsilonRI), specifically binding to the
      alpha-chain (FcepsilonRIalpha), which may be pathogenic. The treatment regimen
      for urticaria needs to be individualized as the severity and clinical pattern can
      vary considerably between patients. Histamine antagonists are the mainstays of
      therapy. For more severe or persistent cases, there are few Food and Drug
      Administration (FDA)-approved options, and there are limited data from controlled
      trials. Further research is required to develop safe and more effective agents
      for this disease.

PMID- 19179824
TI  - Evaluating employee health risks due to hypertension and obesity: self-testing
      workplace health stations.
AB  - BACKGROUND: We evaluated employee health risks due to hypertension, pre
      hypertension, overweight, and obesity through the use of self-testing workplace
      health stations that measure blood pressure (BP) and weight. METHODS: We analyzed
      BP and weight data from the first 18 months after the installation of health
      stations in the offices of a financial services company with approximately 20,000
      employees in 13 US workplace locations. RESULTS: Data showed that 21.7% of the
      employees voluntarily used a health station at least once to measure BP or weight
      during the first 18 months. Health station usage ranged from a high of 51.8% to a
      low of 5.3% at the 13 workplace locations. Among health station users, 52.5% used
      a health station more than once. Health station users used the health stations an
      average of 4.2 times (median, 2 times). Among health station users, 95.6%
      measured BP, 92.2% measured weight, and 87.8% measured both BP and weight.
      Initial BP results were: hypertension 26.7%, prehypertension 40.3%, and normal BP
      32.9%. The initial body mass index (BMI) results were: obese 38%, overweight
      34.7%, normal weight 25.3%, and underweight 2%. Employees with hypertension on
      the initial reading used the health stations more frequently than employees with
      pre-hypertension or normal BP. Employees with an obese BMI result on the initial
      reading used the health stations more frequently than employees with an
      overweight or normal BMI result. Many employees reduced their health risks due to
      hypertension, pre-hypertension, overweight, or obesity, although the health risks
      of many other employees were unchanged or increased. CONCLUSIONS: Self-testing
      workplace health stations that measure BP and weight provide employees with
      information about their health risks due to hypertension, pre-hypertension,
      overweight, and obesity. Self-testing workplace health stations can also be used
      to identify at-risk employees who may benefit from health and wellness programs.

PMID- 19179825
TI  - Puzzles in practice. Sarcoidosis.

PMID- 19179828
TI  - Quality of sleep among hypertensive patients in a semi-urban Nigerian community:
      a prospective study.
AB  - BACKGROUND: Sleep complaints are common in patients with chronic medical
      disorders; however, the prevalence of "poor sleep" in patients with chronic
      hypertension is not yet known in Nigeria. In the general population, insomnia
      negatively impacts quality of life. OBJECTIVE: The objective of this study was to
      examine the quality of sleep among Nigerian hypertensive patients. The study
      aimed to measure the prevalence of "poor sleep" in hypertensive patients and to
      examine the association between quality of sleep and the severity of hypertension
      in this population. METHODS: Quality of sleep was measured using the Pittsburgh
      Sleep Quality Index (PSQI) in chronic hypertensive patients attending a tertiary
      hospital in Nigeria. This was compared with normal control subjects. RESULTS: The
      mean age of the hypertensive patients was 58.15 +/- 9.65 years (range, 19 - 76
      years). This did not differ from the controls at 58.7 +/- 10.8 years. A total of
      80 (60.6%) respondents were females with a mean age of 58.3 +/- 12.2 years while
      52 (39.4%) were males with a mean age of 58.8 +/- 11.7 years. The mean body mass
      index (BMI) was 26.42 +/- 4.13 kg/m2 (range, 18.9 - 36.4 kg/m2), with 63.1% of
      the respondents being either overweight or obese. The mean systolic blood
      pressure was 167.4 +/- 21.8 mm Hg (range, 100 - 210 mm Hg) while the mean
      diastolic blood pressure was 96.7 +/- 14.9 mm Hg (range, 60 - 130 mm Hg). Fifty
      six (42.4%) hypertensive subjects were "poor sleepers" (global PSQI > 5), with a
      global mean PSQI of 5.03 +/- 3.28. This was significantly more than 17.3% of
      control subjects, with a mean global PSQI of 3.10 +/- 0.83. Among the
      hypertensives, there was no statistically significant relationship between the
      global PSQI and the age (P = 0.653), sex (P = 0.710), BMI (P = 0.253), systolic
      (P = 0.145), and diastolic blood pressure (P = 0.827). CONCLUSIONS: Poor sleep is
      common in hypertensive patients and may be associated with lower health-related
      quality of life. Large-scale, prospective, longitudinal studies on quality of
      sleep in hypertensive patients are needed to confirm the high prevalence of
      impaired quality of sleep in this population and to examine the association
      between severity of hypertension and quality of sleep while controlling for
      potential confounding variables. We hypothesize that severity of hypertension
      directly influences quality of sleep, and poor quality of sleep may worsen
      hypertensive conditions.

PMID- 19179829
TI  - Knowledge of diabetes and hypertension care among health care workers in
      southwest Nigeria.
AB  - BACKGROUND: There has been a progressive increase in diabetes among Nigerians. A
      major problem with diabetes care in the sub-Saharan African region is the
      inadequate training of health care workers, leading to insufficient knowledge of
      diabetes and other chronic diseases. AIM: To assess health care workers'
      knowledge on various aspects of diabetes and hypertension management based on
      recommended guidelines. MATERIALS AND METHODS: A questionnaire assessing
      knowledge of diabetes and hypertension care was administered among health care
      workers at the beginning of a workshop on diabetes education. The responses were
      analyzed using SPSS statistical software version 10.0. RESULTS: A total of 184
      subjects responded. One hundred four (56.5%) were male and 80 (43.5%) were
      female. Medical practitioners constituted 76 (41.8%) while nurses and other
      categories of health care workers constituted 46 (25.2%) and 60 (33%),
      respectively. Twenty-eight (26.9%) of these worked in primary health
      institutions, 46 (44.2%) in secondary health institutions, while 30 (28.9%)
      worked in tertiary health institutions. One hundred eighteen (64.1%) respondents
      gave a correct response of 5 to 6 mmol/L (90 - 108 mg/L) as the blood glucose
      target level for diabetic patients. Similarly, 118 (64.1%) respondents gave a
      correct response of < or = 130/85 mm Hg as the recommended target blood pressure
      for diabetic patients. The ideal serum cholesterol of 5.0 mmol/L and glycated
      hemoglobin were correctly indicated by 42 (22.8%) and 56 (30.4%) of the
      respondents, respectively. The majority of the subjects (89.1%) were aware of the
      fact that tight blood glucose control reduces the risk of diabetes-related
      complications. The variables that correlated with increased knowledge include
      treating more than 50 patients per month (X2 4.124, P = 0.042) and working in a
      tertiary center (X2 5.714, P = 0.047). Most of the health care facilities (61.7%)
      where the respondents work do not deliver protocol-driven care for diabetics.
      CONCLUSION: A large number of health care workers in southwest Nigeria do not
      seem to be familiar with the current practice guidelines for the management of
      diabetes. There is a need to introduce protocol-driven diabetes care in our
      health care facilities and improve the knowledge base of practitioners.

PMID- 19179830
TI  - Management of very elderly hypertensives: the HYVET study.

PMID- 19179831
TI  - Reliability of equations to estimate glomerular filtration rate in the very old.
AB  - BACKGROUND AND AIMS: Few studies have investigated the reliability of formulas
      estimating renal function in very old people. METHODS: We studied 154 elderly
      people (mean age: 82 yrs). Serum creatinine (SC) was measured by the Jaffe
      method, and creatinine clearance (CrCl) with 24-h urine collection. Agreement was
      measured with the average ratio estimated/measured CrCl, and precision with the
      95% agreement intervals (95% AI). We calculated the proportion of residents
      correctly classified as having renal insufficiency (accuracy). RESULTS: The
      Cockcroft-Gault (CG) and Modification of Diet in Renal Disease 1 (MDRD1) formulas
      showed good average agreement with measured CrCl (0.95 and 1.016, respectively);
      the MDRD2 formula was more biased. Results were consistent in women, whereas the
      MDRD1 was more biased in men (average ratio: 1.196). The 95% AI showed that all
      formulas can yield results as low as 50% or as high as 200% of measured CrCl. The
      proportion of people with CrCl<60 ml/min misclassified by the CG, MDRD1, and
      MDRD2 formulas as having normal renal function was 21.4%, 27.0%, and 38.8%,
      respectively. These results were consistent across the various subgroups,
      especially in subjects with normal SC. CONCLUSIONS: The clinical usefulness of
      formulas commonly used to estimate CrCl was limited, regardless of subjects'
      characteristics.

PMID- 19179832
TI  - Interaction of age and specific saliva component output on caries.
AB  - BACKGROUND AND AIMS: The purpose of this study was to explore the relationship
      between individual salivary components, dental caries and age, utilizing the data
      from the Oral Health: San Antonio Longitudinal Study of Aging (OH:SALSA).
      METHODS: The study population comprised a well-defined stratified sample of 811
      dentate men and women. Subjects were divided into four age groups from 35 to 75+
      years old. Unstimulated and stimulated submandibular/sublingual saliva flow
      rates, unstimulated and stimulated parotid saliva flow rates, total protein, 6
      individual proteins and 4 inorganic constituents were measured. Specific salivary
      components were lactoferrin, secretory IgA, albumin, lysozyme, mucin, cystatin,
      K+, Ca2+, Na+ and Cl-. Caries measurements were the DMFT Index for crowns and for
      roots, Tooth Health Index for crowns and roots, Tooth caries, Root caries and
      Tooth restoration. The data on saliva components were square root transformed for
      linearity prior to analysis. Analysis was carried out in two stages. Partial
      correlation was performed, in order to identify significant relationships between
      specific salivary components and caries measurements, controlling for age group.
      In the second stage, using caries measurement as the dependant variable, the
      effects of age, flow rate and specific salivary component output (product of flow
      rate and concentration) were examined. RESULTS: Significant associations were
      found between caries, age and specific individual submandibular/sublingual
      salivary proteins (lactoferrin, albumin, lysozyme, mucin and cystatin) and
      specific inorganic constituents (K+, Ca2+, Na+ and Cl-). CONCLUSIONS: Changes in
      submandibular/ sublingual salivary component output during aging are correlated
      with high caries prevalence. These changes in saliva components over age may
      represent caries risk indicators.

PMID- 19179833
TI  - Serum albumin level interferes with the effect of donepezil in Alzheimer's
      disease.
AB  - BACKGROUND AND AIMS: The most successful therapeutic approaches to Alzheimer's
      disease (AD) have involved acetylcholinesterase inhibitors (ChEIs). In view of
      the different response rates to ChEIs therapy, it is important to identify the
      pharmacokinetic and pharmacodynamic mechanisms which may interfere with this
      effect. The aim of the study is to evaluate the efficacy on cognition of
      donepezil, a cholinesterase inhibitor, in a sample of mild to moderate AD
      patients with various serum albumin levels, a condition modifying drug
      distribution. METHODS: Ninety-eight Alzheimer patients treated with donepezil
      were analyzed in an outpatient clinic between January 2003 and January 2005. At
      study entry, participants underwent multidimensional assessment evaluating
      cognitive, functional and psychobehavioral domains. All concomitant illnesses and
      treatments were recorded. Patients were grouped in three categories (with low,
      medium and high albumin levels). RESULTS: The total sample of patients showed
      cognitive improvement from baseline of the ADAS Cog score at three months (ADAS
      Cog mean change -1.4+5.4; p=0.01), cognitive stabilization at nine (ADAS Cog mean
      change 0.03+6.7; p=ns), and not statistically significant worsening at fifteen
      months (ADAS Cog mean change 0.9+7.3; p=ns). The low serum albumin level group
      was associated with a greater response to donepezil. In fact, cognition,
      evaluated by the ADAS Cog mean change from baseline, improved during the first 15
      months of treatment in the low serum albumin level group, but worsened in the two
      higher groups. CONCLUSION: Our preliminary data suggest that serum albumin level
      should be monitored to evaluate the clinical efficacy of ChEIs therapy.

PMID- 19179835
TI  - The role of vitamin E in reversing bone loss.
AB  - BACKGROUND AND AIMS: A positive correlation between intake of antioxidants
      including vitamins E and C on bone mass has been established by a number of
      investigators. The present study was conducted to evaluate the extent to which
      higher doses of vitamin E than normal dose (75 IU per kg diet) can reverse bone
      loss in aged osteopenic orchidectomized male rats. METHODS: Forty 12-month old
      male Sprague- Dawley rats were either sham-operated (Sham) or orchidectomized
      (Orx), and fed control diet for 120 days to establish bone loss. Thereafter, rats
      were assigned to their corresponding treatment groups (n= 10 per group): Sham and
      one Orx groups received 75 IU vitamin E and served as controls, and the other two
      Orx groups received either 250 or 500 IU vitamin E per kg diet for 90 days.
      RESULTS: Higher doses of vitamin E did not improve bone mineral density (BMD) or
      content (BMC) of whole body, femur and lumbar vertebra or alter the orchidectomy
      induced deterioration of trabecular microarchitecture of the distal femur
      metaphysis in comparison with Orx controls that received adequate vitamin E.
      Biochemical markers of bone formation and bone resorption, i.e. serum osteocalcin
      and urinary deoxypyridinoline crosslinks, were also unaffected by vitamin E
      supplementation. CONCLUSIONS: Overall, the findings of the present study suggest
      that supplemental doses of vitamin E do not increase BMD values in male rat model
      of osteoporosis. However, human studies are needed to confirm the population
      findings indicating that individuals with higher vitamin E intake have higher
      bone mass.

PMID- 19179834
TI  - Use of cereal fiber to facilitate adherence to a human caloric restriction
      program.
AB  - BACKGROUND AND AIMS: Caloric restriction (CR) attenuates biological aging in
      animal models but there is little information on the feasibility and efficacy of
      CR regimens in humans. We examined the effects of consuming an insoluble cereal
      fiber supplement on ability to sustain CR over 1 year in healthy overweight
      adults. METHODS: In 34 healthy overweight women and men (BMI 25-30 kg/m2, age 20
      42 yr), a 30% CR regimen meeting national recommendations for dietary fiber was
      provided for 24 weeks, and for an additional 24 weeks subjects were counseled to
      prepare the same regimen at home. During 5-10 weeks of CR, subjects were
      randomized to consume an extra 20 g/day of dietary fiber from a high fiber cereal
      (+F) or to not consume additional fiber (-F). After this time, all subjects were
      encouraged to consume the extra fiber. Outcomes included adherence to the
      provided and self-prepared CR regimens (energy intake determined using doubly
      labeled water), changes in body weight, and self-reported satisfaction with the
      amount of consumed food. RESULTS: During 5-10 weeks of CR when all food was
      provided, both +F and -F groups were highly adherent to the CR regimen and there
      was no significant difference between groups in energy intake (p=0.51), weight
      change (p=0.96), or satisfaction with amount of provided food (p=0.08). During
      self-prepared CR from 25 to 48 weeks, mean adherence was lower than during the
      food-provided phase and there was a significant association between fiber intake
      and % CR (r=0.69, p<0.001), decreased BMI (r=- 0.38, p=0.04) and satisfaction
      with the amount of consumed food (r=0.59, p=0.002). CONCLUSIONS: A high fiber
      cereal intake may facilitate CR in humans self-selecting their own food; longer
      term intervention studies are needed to confirm these findings.

PMID- 19179836
TI  - Common drug switching during long-term antiresorptive treatment: experience of
      four osteoporosis centers in Poland (2001-2005).
AB  - BACKGROUND AND AIMS: In clinical trials, the most frequent reasons for treatment
      discontinuation are adverse events and personal conflicts with medical staff.
      However, in "real life", i.e. not in the frame of a controlled and monitored
      trial, other reasons are also possible, when not only discontinuation, but also
      switching of treatment happens. The aim of this study was to estimate how often
      and why persistent osteoporosis patients switch from one treatment to another.
      METHODS: A retrospective analysis of 1314 ambulatory treated persistent
      osteoporosis patients was performed (1180 F, 134 M, mean age+/-SD: 66.5+/-10 yrs,
      BMI 26.4+/-4.2 kg/m2). Drugs used for osteoporosis, duration of treatment,
      frequency and reasons for drug switching were all analyzed. RESULTS: In 530
      (40.3%) patients, treatment was not changed during the observation period (16.1+/
      9.1 months). In 784 (59.7%) patients at least one drug switch happened, and the
      total number of switches was 1117 (1- 5 switches/patient). The mean time of
      observation in this group was 22.3+/-14.9 months. The most frequent reasons for
      drug switching were: adverse event (34.6% of all switches), high price of the
      drug (28.7%) and ineffective treatment (13.3%). CONCLUSIONS: In almost 60% of the
      persistent patients, at least one switch of antiosteoporotic treatment occurred
      in the nearly 2- year observation period. The most frequent reasons for drug
      switching were adverse reactions, the high price of the drug, and ineffective
      treatment.

PMID- 19179837
TI  - Admission profile is predictive of outcome in acute hospital care.
AB  - BACKGROUND AND AIMS: The purpose of this study is to describe predictors for
      discharge and one-year outcomes of acute-care hospital patients, 75 years of age
      or over, based on admission status information. We carried out a prospective
      study of a randomly selected patient population, from one urban acute-care
      hospital in each of the Nordic countries. 763 persons aged 75+ were randomly
      selected from acute admissions to the participating hospitals. 749 observations
      at discharge and 655 observations at one year were used in analyses. METHODS:
      Data were collected with the MDS-AC 1.1 instrument within 24 hours of admission,
      and at day 7 or discharge, whichever came first. Outcome information was
      collected either by interviewing the patient or from patient records or
      registers. Discharge and one-year outcome (home, institution, death) were modeled
      by multinomial logistic regression, with admission status variables as
      predictors. RESULTS: At discharge, 84% of subjects returned home, 11% went to an
      institution and 5.6% had died. At one year, 64% were still living at home, 24%
      had died, and 12% had moved to an institution. For discharge outcome, those
      having hospital admission due to a new problem or exacerbation of an old one had
      a higher risk of dying (OR 3.3) than returning home. Moderate to severe cognitive
      problems predicted death (OR 2.2) and institutionalization (OR 8.6) compared with
      discharge home. Problems in instrumental activities of daily living predicted
      death (OR 3.1) and institutionalization (OR 6.0). At one year, those with
      exacerbation of an old problem (OR 2.1) or with a new or exacerbated existing
      problem (OR 2.3) had a higher risk of dying than of institutionalization or
      discharge home. Having some cognitive problems (OR 2.8) or moderate to severe
      cognitive problems (OR 6.6) predicted institutionalization, but not dying or
      discharge home. Those with some problems in activities of daily living had a
      higher risk of both dying (OR 1.7) and of institutional care (OR 2.7). Those with
      moderate to severe problems in activities of daily living had also a higher risk
      of institutional care (OR 4.7) compared with those living at home. CONCLUSIONS:
      Evidence predictive of discharge and one-year outcomes in older acute hospital
      medical care patients seems to be visible from the beginning of the hospital
      stay. In order to increase the efficient use of health care services and quality
      of care, systematic standardized and streamlined assessment should be performed
      during the admission process.

PMID- 19179838
TI  - Peripheral arterial disease, diabetes and postural balance among elderly Finns: a
      population-based study.
AB  - BACKGROUND AND AIMS: Little is known about the role of peripheral arterial
      disease (PAD) in the development of balance impairment. The aim of this study was
      to assess postural balance among people having PAD or PAD combined with diabetes.
      METHODS: As part of the comprehensive health examination of the Health 2000
      survey (two-stage stratified cluster sampling), 1323 people aged 65 years or
      older took part in balance assessments using a force platform system. The
      presence of PAD was confirmed with data from the National Hospital Discharge
      Registry. Individuals with hospitalization due to PAD were regarded as having
      severe disease, whereas those with solely self-reported diagnosis were considered
      possible cases. Diabetes was ascertained on the basis of self-reported
      physicians' diagnoses subsequently confirmed in a clinical examination. RESULTS:
      Forty-five (3.4%) individuals had previously been hospitalized due to PAD, and 32
      (2.4%) reported that they had been diagnosed with the disease. 413 (31%)
      participants had diabetes. Compared with people without PAD, those with confirmed
      diagnoses exhibited significantly increased movement of the center of pressure
      while standing, indicating deteriorated balance. Those with possible PAD formed
      an intermediate group. Diabetes exacerbated the deterioration in balance, but the
      interaction term between PAD and diabetes did not reach statistical significance.
      The risk of failing tandem stance tests was over three-fold (OR 3.20, 95% CI 1.09
      9.37) among those with confirmed PAD and almost one and a half-fold (OR 1.44, 95%
      CI 1.07-1.93) among those with diabetes, in comparison to those without these
      diseases. CONCLUSIONS: Individuals over 65 years of age with severe PAD showed
      increased balance impairment, a known risk factor for falls and disability in
      aged people. Diabetes affected balance somewhat less than PAD, but there was no
      formal evidence of the synergetic effect of the two diseases. Additional studies
      are indicated to reveal the possible effect of proper treatment of PAD and
      diabetes, combined with suitable training interventions on slowing down the
      progression of balance impairment.

PMID- 19179839
TI  - Healthcare costs for people aged 65+ two years prior to their receiving long-term
      municipal care.
AB  - BACKGROUND AND AIMS: More knowledge is needed about patterns of healthcare
      consumption at different times during old age, particularly with regard to the
      relationship between various agents in the healthcare and social services system.
      One aim was to investigate healthcare costs in the public medical healthcare
      system in men and women (65+) and, with regard to age, in the two years prior to
      the start of long-term municipal care and services. Another aim was to
      investigate patterns and determinants of costs. METHODS: The study comprised 362
      people who received decisions about municipal care and/or services during 2002
      2003, and data were derived from the Swedish National Study of Aging and Care
      (SNAC) and county councils registers about healthcare consumption. SNAC provided
      data concerning demographics, functional dependency and informal care at the time
      of the decision, which were merged with data from the Skane County Council
      patient administrative system regarding costs in the two years prior to decision.
      RESULTS: Cluster analysis revealed 13% overall higher healthcare costs. Those
      involved were more often younger, men, married, and diagnosed with circulatory
      diseases, cancer, or injuries. Most (58% for women, 54% for men) of the costs for
      acute inpatient care occurred within five months prior to municipal care. Men had
      significantly higher costs compared with women for visits to outpatient
      physicians (EUR 700 vs 400) and inpatient care (EUR 4700 vs 700) 12-0 months
      prior to municipal care. CONCLUSIONS: A share of 13% had higher healthcare costs
      throughout the two years. Those involved were more often younger, men, married,
      and diagnosed with circulatory diseases, cancer, or injuries. Those older people
      at risk of high healthcare costs should benefit from systematic clinical
      assessments and more proactive and integrated care, to prevent escalating costs
      in the period preceding long-term municipal care and services.

PMID- 19179840
TI  - The effects of interdisciplinary outpatient geriatrics on the use, costs and
      quality of health services in the fee-for-service environment.
AB  - BACKGROUND AND AIMS: To evaluate the effect of interdisciplinary outpatient
      geriatrics on the use, cost, and quality of health services in a fee-for-service
      (FFS) environment of two networks of primary care clinics operated by a not-for
      profit provider organization in Dallas County, Texas. METHODS: The Senior Health
      Network (SHN) provides interdisciplinary primary care to patients aged 55 years
      or older; the Health Texas Provider Network (HTPN) provides "usual" primary care
      to patients of all ages. We conducted a two-year retrospective cohort study of
      13,098 fee-for-service Medicare beneficiaries who had 2+ visits to one of the
      networks in 2000. In the SHN, interdisciplinary teams supplemented primary care
      with social services, specialized clinics, and health education. We compared the
      use, cost and quality of health services, as reflected by paid Medicare claims,
      provided to eligible patients in the SHN vs the HTPN. RESULTS: Medicare payments
      for hospital, skilled nursing facility, and home health care services were lower
      for SHN patients than HTPN patients (-32.7%, -19.8%, and -23.8%, respectively,
      p<or=0.05). SHN patients had a lower likelihood of admission to hospitals for
      treatment of five "ambulatory care sensitive conditions" (aOR 0.69, 95% CI 0.58-
      0.81), and they were less likely to receive several preventive services. Total
      Medicare payments for the two cohorts did not differ significantly. CONCLUSIONS:
      Interdisciplinary outpatient geriatric care in a FFS setting has the potential to
      avert hospital admissions for ambulatory care sensitive conditions and to reduce
      Medicare payments for hospital, skilled nursing facility, and home health care
      services.

PMID- 19179841
TI  - Association of cognitive impairment, activity limitation with latent traits in
      the GHQ-12 in the older elderly. The Bambui Health and Aging Study (BHAS).
AB  - BACKGROUND: The 12 item-General Health Questionnaire (GHQ-12) is the shortest
      version of GHQ. The questionnaire works as well as the longer instruments and is
      used more frequently in epidemiological surveys. It is an effective instrument
      for aging studies because of its brevity and absence of somatic symptoms.
      Previous studies of Principal Component Analysis (PCA) were carried out in adult
      populations only, demonstrating two- and three-factor solutions. METHODS: This
      study involved 392 participants over 75 years old in a population-based survey in
      Bambui, Brazil. Both PCA and Confirmatory Factor Analysis (CFA) were performed.
      In CFA, several factor structures were compared using different goodness-of-fit
      indices. (The association between factor scores of the model with the best fit
      and participant characteristics were analyzed by linear regression). RESULTS: PCA
      suggested a three-factor model. Graetz's three-factor solution (Anxiety
      Depression, Social Dysfunction and Loss of Confidence) was the best model in CFA
      according to goodness-of-fit indices. Activity limitation and poor self-reported
      global health were associated with the anxiety/depression and social dysfunction
      factors. Cognitive impairment and female gender were associated with social
      dysfunction. Loss of confidence was not associated with these or other relevant
      variables. CONCLUSION: The three-factor solution proposed by Graetz seems to be
      the best fit also for people over 75 years old. Further studies are needed to
      understand the conceptual and practical relevance of these underlying factors,
      particularly loss of confidence in the elderly population.

PMID- 19179842
TI  - Aging and prospective memory: the role of working memory and monitoring
      processes.
AB  - BACKGROUND AND AIMS: Remembering to execute an earlier planned action is
      essential in everyday life, and is a prerequisite for independent living in old
      age. The purpose of the present study was to determine the influence of age in
      performing a prospective memory (PM) task and to analyze the differential
      contribution of working memory and attentional monitoring demands. METHODS: In
      Experiment 1, a group of young and two groups of old adults were assigned to one
      of two low-demanding conditions: a picture-naming task (only-Naming) and a
      picture-naming plus a PM task (Naming+PM). In Experiment 2, a group of young and
      two groups of old adults performed one of two high-demanding conditions, in which
      working memory and attentional monitoring processes were examined, using a
      listening span-like task and a 1-back task within the PM paradigm of Experiment
      1. RESULTS: Prospective memory performance declined with age even in the low
      demanding condition (Experiment 1). Young participants showed PM failures only
      when the 1-back task was added to the low-demanding condition. Older participants
      exhibited a marked decline, particularly in the working memory load condition.
      CONCLUSIONS: These results suggest that even low-demanding prospective memory
      tasks are resource-consuming in old age, and that working memory efficiency,
      affected by the aging process, plays a crucial role in the successful
      accomplishment of PM actions.

PMID- 19179843
TI  - Attention and aging.
AB  - BACKGROUND AND AIMS: Aging is a condition characterized by a general decline in
      many types of physical and psychological performance, but its effects on various
      cognitive functions are still controversial. When viewed along a time-course,
      several abilities clearly differ in their stability or decline with aging. Among
      psychological functioning in the elderly, changes in attention are not fully
      understood. The aim of our research was to analyze attentive performance in a
      sample of subjects aged 55-65, evaluating various aspects of attentive
      functioning with respect to the gender variable and to verify if aging affects
      all attentive functions equally. METHODS: The sample included 80 subjects (44
      men, 36 women) of 55-65 years of age. Attentional abilities were evaluated by
      means of multitask computerized assessment. The test involved seven tasks
      assessing simple reaction times and choice reaction times, visual, visual-spatial
      and auditory selectivity, digit span, divided attention, resistance to
      distraction, and attentive shifting. RESULTS: Significant differences related to
      gender were found in attention shifting. To test possible decline in attentive
      function with age, performances among two age groups (55-59 and 60-65 yrs) were
      compared. Significant differences were shown in simple immediate attention span,
      selectivity, capacity to inhibit interference of non-pertinent signals, and
      attentive shifting. CONCLUSIONS: This study demonstrates an age-related reduction
      in attentive efficiency but, notably, this decline does not involve all
      components of attention. Subjects over 60 years of age show progressive slowing
      in processing of complex tasks and a reduced capacity to inhibit irrelevant
      stimuli.

PMID- 19179845
TI  - Hepatotoxicity after intravenous amiodarone.
AB  - Amiodarone is a class III antiarrhythmic agent with a long half-life which is
      used to control atrial and ventricular arrhythmias, including atrial flutter and
      fibrillation. We describe here the case of an elderly woman (77 years of age) who
      was hospitalized for acute atrial fibrillation, abdominal pain, and dyspnea. In
      the Emergency Department, treatment with intravenous amiodarone was begun. The
      following day, the patient developed acute liver damage; improved liver function
      occurred following the withdrawal of amiodarone. Complete recovery of liver
      function was documented after three weeks. Unfortunately, the patient died from a
      severe infectious disease, with multiple organ failure.

PMID- 19179844
TI  - Depressive symptomatology and fracture risk in community-dwelling older men and
      women.
AB  - BACKGROUND AND AIMS: Previous studies suggest that depression increases risk of
      falls, low bone mineral density, and fractures. Our aim was to evaluate whether
      depressive symptomatology alone predicts 5- year clinical fracture risk in older
      adults. METHODS: In this secondary analysis of a community-based, prospective
      cohort study including 4175 women and 1652 men in Canada, depressive
      symptomatology was assessed at baseline by the mental health inventory-5 (MHI-5)
      and the mental component score (MCS) of the short form 36 questionnaire (SF-36).
      Fracture events were assessed annually for five years; all reported incident
      fragility fractures were confirmed radiographically. RESULTS: Depressive
      symptomatology did not predict time to first fracture in men (hazard ratio [HR]
      0.86, 95% confidence interval [CI] 0.45-1.65) or women (HR 1.09, 95% CI 0.86
      1.39). Results were similar after controlling for potential confounders.
      Depressive symptoms were not significantly associated with baseline bone mineral
      density at the lumbar spine or femoral neck. Women with depressive symptoms were
      more likely to report falls in the previous month (odds ratio [OR] 1.52, 95% CI
      1.12-2.06, p=0.01). This association did not achieve statistical significance in
      men (OR 1.71, 95% CI 0.96-3.04, p=0.07). CONCLUSION: In this large, community
      cohort, depressive symptomatology did not predict five-year risk of clinical
      fracture. Further research is needed to determine if individuals with major
      depressive disorder (MDD) are at higher fracture risk and whether neuroendocrine
      or hormonal dysregulation might contribute to such risk in MDD.

PMID- 19179847
TI  - Genetics of dopamine receptors and drug addiction: a comprehensive review.
AB  - Drug dependence is a chronic, relapsing disorder in which compulsive drug-seeking
      and drug-taking behaviours persist despite serious negative consequences.
      Addictive substances, such as opioids, ethanol, psychostimulants and nicotine,
      induce pleasant states or relieve distress, effects that contribute to their
      recreational use. Dopamine is critically involved in drug addiction processes.
      However, the role of the various dopaminergic receptor subtypes has been
      difficult to delineate. Here, we will review the information collected
      implicating the receptors of the D1 family (DRD1 and DRD5) and of the D2 family
      (DRD2, DRD3 and DRD4) in drug addiction. We will summarize the distribution of
      these receptors in the brain, the preclinical experiments carried out with
      pharmacological and transgenic approaches and the genetic studies carried out
      linking genetic variants of these receptors to drug addiction phenotypes. A meta
      analysis of the studies carried out evaluating DRD2 and alcohol dependence is
      also provided, which indicates a significant association. Overall, this review
      indicates that different aspects of the addiction phenotype are critically
      influenced by dopaminergic receptors and that variants of those genes seem to
      influence some addiction phenotypes in humans.

PMID- 19179848
TI  - Mutant mouse models and antidepressant drug research: focus on serotonin and
      brain-derived neurotrophic factor.
AB  - Several lines of knockout (KO) mice have been evaluated as models of depression
      related behavioral and neurobiological changes, and used to investigate molecular
      and cellular mechanisms underlying the activity of antidepressant drugs. Adult
      neurogenesis and brain 5-hydroxytryptamine (5-HT)/neurotrophic factor
      interactions have recently attracted great interest in relation to the mechanism
      of action of antidepressant drugs. The present review focuses primarily on
      genetic manipulation of the serotoninergic (5-HT) system. Basal neurochemical and
      behavioral changes occurring in mice lacking the 5-HT transporter (SERT), which
      is the main target of antidepressant drugs, as well as in those lacking G protein
      coupled serotonin receptors (e.g. 5-HT1B, 5-HT1A, and 5-HT4 receptors) are
      described and evaluated. The importance of KO mice for neurotrophic factors,
      particularly for brain-derived neurotrophic factor and its high-affinity receptor
      (R-TrkB), is also addressed. Constitutive KO, tissue specific, or inducible KO
      mice targeting both 5-HT and brain-derived neurotrophic factor systems may
      potentially make an important contribution to knowledge of the pathophysiology
      and treatment of depression.

PMID- 19179849
TI  - Relative potency and effectiveness of flunitrazepam, ethanol, and beta-CCE for
      disrupting the acquisition and retention of response sequences in rats.
AB  - Despite the knowledge that gamma-aminobutyric acid(A) modulators can affect
      learning and memory, their capacity for disrupting each of these complex
      processes is rarely compared, and often mistakenly assumed to occur with
      identical potency. For these reasons, the effects of flunitrazepam (0.056-3.2
      mg/kg), ethanol (0.25-1.5 g/kg), and ethyl-beta-carboline-3-carboxylate (beta
      CCE; 1-17.8 mg/kg) were compared in groups of rats responding under baselines
      that assessed learning and memory separately. The first baseline was a multiple
      schedule of repeated acquisition and performance of tandem response sequences,
      whereas the second baseline was a retention or memory procedure where a tandem
      response sequence was acquired and then retested after a 30-min delay. Under both
      procedures, responding was maintained under a second-order fixed-ratio-2 schedule
      of food reinforcement, and incorrect responding (errors) produced a 5-s timeout.
      With regard to the effects of the three drugs on sequence acquisition (learning),
      all three drugs dose dependently decreased the overall response rate and
      increased the percentage of errors. Both flunitrazepam and beta-CCE affected
      accuracy more potently than response rate, whereas ethanol was equipotent in
      affecting these two dependent measures. With regard to the effects of these drugs
      on sequence retention (memory), both flunitrazepam and ethanol dose dependently
      decreased retention at doses that had little or no effect on sequence acquisition
      under the multiple schedule, whereas beta-CCE decreased retention and sequence
      acquisition similarly at the doses tested. Together, these data show that drugs
      with differing capacities for altering the function of gamma-aminobutyric acid(A)
      receptors differ in their capacity for disrupting the acquisition and retention
      of response sequences and that positive modulation of this receptor complex may
      be more predictive of disruptions in memory than disruptions in learning.

PMID- 19179850
TI  - Chronic treatment with Delta(9)-tetrahydrocannabinol impairs spatial memory and
      reduces zif268 expression in the mouse forebrain.
AB  - Few studies have investigated the effects of chronic cannabinoid exposure on
      memory performance and whether tolerance occurs to cannabinoid-induced memory
      impairment. Here, we studied the effects of repeated exposure to Delta
      tetrahydrocannabinol (THC: 1 mg/kg) on spatial memory and zif268 expression in
      mice. One group of animals was not pretreated with THC, whereas another group was
      injected with 13 daily injections of THC before memory testing in the Morris
      water maze. Both groups were administered with THC throughout the memory-testing
      phase of the experiment. THC decreased spatial memory and reversal learning, even
      in animals that received the THC pretreatment and were tolerant to the locomotor
      suppressant effects of the drug. Zif268 immunoreactivity was reduced in the CA3
      of the hippocampus and in the prefrontal cortex only in non-pretreated animals,
      indicating that although tolerance to the effects of THC on neuronal activity was
      evident, cannabinoid-induced memory impairment in these animals persisted even
      after 24 days of exposure. This study shows that after extended administration of
      THC, its spatial memory-impairing effects are resistant to tolerance.

PMID- 19179851
TI  - Effects of a metabotropic glutamate receptor group II agonist LY354740 in animal
      models of positive schizophrenia symptoms and cognition.
AB  - It has been proposed that activation of metabotropic glutamate receptor subtype
      2/3 (mGluR2/3) may induce both antipsychotic and anxiolytic effects. The aim of
      this study was to evaluate further the effect of the mGluR2/3 agonist, LY354740
      [(+)-2-aminobicyclo(3.1.0)hexane-2,6-dicarboxylate monohydrate] in animal models
      relevant to both psychotic and cognitive impairment in schizophrenia. The
      elevated plus maze was used to select the doses for further experiments, LY354740
      induced anxiolytic-like effects at doses of 3 and 10 mg/kg but not 1 mg/kg. At a
      dose of 10 mg/kg. LY354740 attenuated phencyclidine (PCP)-induced locomotor
      activity. Administered alone, it had no effect on horizontal activity, but at
      doses of 3 and 10 mg/kg, slightly decreased vertical activity (rearings).
      LY354740 (1-10 mg/kg intraperitoneally) affected neither prepulse inhibition in
      normal rats nor reversed the disruption of prepulse inhibition produced by PCP (2
      mg/kg subcutaneously). Moreover, LY354740 (3-10 mg/kg) did not modify PCP-induced
      working memory deficits assessed in a spontaneous alternation task and had no
      effect on PCP-evoked amnesia in the passive avoidance test. LY354740 alone (3 and
      10 mg/kg) induced working memory deficits, but had no effect on acquisition of
      passive avoidance. In conclusion, LY354740 was effective in models for anxiety
      and positive symptoms of schizophrenia but not in models for sensorimotor gating
      and cognitive impairment.

PMID- 19179852
TI  - Olanzapine and risperidone disrupt conditioned avoidance responding in
      phencyclidine-pretreated or amphetamine-pretreated rats by selectively weakening
      motivational salience of conditioned stimulus.
AB  - The rat conditioned avoidance response model is a well-established preclinical
      behavioral model predictive of antipsychotic efficacy. All clinically approved
      antipsychotic drugs disrupt conditioned avoidance responding - a feature that
      distinguishes them from other psychotherapeutics. We previously showed that the
      typical antipsychotic drug haloperidol disrupts avoidance responding by
      progressively attenuating the motivational salience of the conditioned stimulus
      (CS) in normal rats. In this study, using two pharmacological rat models of
      schizophrenia [e.g. phencyclidine (PCP) or amphetamine sensitization], we
      examined whether atypicals such as olanzapine or risperidone disrupt avoidance
      responding through the same behavioral mechanism. Rats were first pretreated with
      PCP, amphetamine, or saline under one of two different injection schedules for
      either 1 or 3 weeks. They were then trained to acquire avoidance responding to
      two types of CS (CS1 and CS2) that differed in their ability to predict the
      occurrence of the unconditioned stimulus. Finally, rats were tested repeatedly
      under olanzapine (1.0 mg/kg, subcutaneously) or risperidone (0.33 mg/kg,
      subcutaneously) daily for 5 or 7 consecutive days. We found that repeated
      olanzapine or risperidone treatment produced a progressive across-session decline
      in avoidance responding to both CS1 and CS2. Olanzapine and risperidone disrupted
      the CS2 (a less salient CS) avoidance to a greater extent than the CS1 avoidance.
      Pretreatment with PCP and amphetamine did not affect the disruptive effect of
      olanzapine or risperidone on avoidance responding. On the basis of these
      findings, we suggest that the atypical drugs olanzapine and risperidone, like the
      typical drug haloperidol, also disrupt avoidance responding primarily by
      attenuating the motivational salience of the CS.

PMID- 19179854
TI  - Exposure to acute restraint stress reinstates nicotine-induced place preference
      in rats.
AB  - Tobacco addiction is associated with high rates of relapse to drug use even after
      prolonged periods of abstinence. Relapse can occur upon reexposure to the drug of
      abuse, exposure to stress or to stimuli associated with drug consumption. The
      reinstatement of conditioning place preference (CPP) provides a simple and easy
      approach to investigate the mechanisms for drug relapse. We evaluated whether
      exposure to restraint stress could reinstate nicotine-induced CPP 1 or 15 days
      after its extinction. Nicotine produced place preference to the compartment
      paired with its injections during conditioning (0.16 mg/kg, subcutaneous; four
      drug sessions). Once established, nicotine CPP was extinguished by alternate
      exposure to each compartment after a saline injection (four exposures to each
      compartment). After this extinction phase, the reinstatement of place
      conditioning was investigated. For this purpose, rats were exposed to 30-min
      restraint stress 1 or 15 days after the extinction test, then immediately tested
      for reinstatement of CPP. Our results show that exposure to restraint stress
      reinstated CPP 1 and 15 days after extinction. Our study indicates for the first
      time that the vulnerability to stress-induced reinstatement of nicotine CPP is
      long-lasting, corroborating clinical studies showing that stress is positively
      associated with relapse to tobacco use even after a long period of nicotine
      withdrawal.

PMID- 19179853
TI  - Nicotine does not enhance discrimination performance in a temporal bisection
      procedure.
AB  - Recent reports of selective disruption of stimulus control by drug administration
      and other disruptive operations in temporal discrimination procedures may be
      interpreted as a disruption of attention to the temporal sample stimuli. This
      experiment assessed the effects of nicotine, a compound that has been widely
      shown to increase measures of attention, on temporal discrimination performance.
      Pigeons responded under a psychophysical choice procedure in which responses to
      one key color were correct after presentation of four shorter sample durations
      and responses to another key color were correct after presentation of four longer
      sample durations. Performance under nicotine was characterized by using a model
      that differentiates the effects of nicotine on stimulus control, bias, and
      sensitivity of temporal discrimination. Nicotine selectively decreased the
      measure of stimulus control, but did not systematically affect the measures of
      timing. Mecamylamine (1.0 mg/kg) failed to antagonize the disruptive effects of
      nicotine. These results suggest that disruption of temporal discrimination
      performance in this preparation may not have been dependent on the specific
      pharmacology of nicotine and underscore the importance of quantitative separation
      of the effects of various manipulations on stimulus control from effects on
      timing.

PMID- 19179855
TI  - WAY 100635 produces discriminative stimulus effects in rats mediated by dopamine
      D(4) receptor activation.
AB  - In-vitro studies have shown that WAY 100635 is not only a potent 5-HT1A
      antagonist, but also has high affinity and efficacy at the dopamine D(4)
      receptor. Nevertheless, the behavioral effects of this compound have not been
      investigated. This study sought to characterize the discriminative stimulus
      effects produced by WAY 100635. Male Sprague-Dawley rats were trained in a two
      lever, fixed ratio 50, food-reinforced task with WAY 100635 (10 micromol/kg) as a
      discriminative stimulus. Substitution tests with different doses of WAY 100635
      and (-)-pindolol, and combination tests with two 5-HT1A agonists, 8-OH-DPAT and
      LY 293284; and two dopamine D(4) antagonists, sonepiprazole and A-381393, were
      performed. Rats trained with a low dose (0.74 micromol/kg) of WAY 100635 could
      not learn the discrimination task after more than 3 months of sessions. Rats
      trained to discriminate 10 micromol/kg of WAY 100635 from saline achieved the
      criterion of accuracy after approximately 35 training sessions. WAY 100635 (2.5
      10 micromol/kg) produced a dose-dependent increase in WAY 100635-appropriate
      responding, with a mean effective dose of 3.44 micromol/kg, whereas saline or
      pindolol (5-25 micromol/kg) administration resulted in 0% drug lever responding.
      Pretreatment with the 5-HT(1A) agonists 8-OH-DPAT or LY 293284 did not modify the
      WAY 100635 curve, but pretreatment with the selective dopamine D(4) antagonists
      sonepiprazole or A-381393 completely blocked the cue. These results indicate that
      the discriminative stimulus effect produced by WAY 100635 is mediated by
      activation of dopamine D(4) receptors.

PMID- 19179857
TI  - We put together the following series of topics: imaging of acute pelvic pain,
      multimodality imaging of benign adnexal masses, ovarian cancer detection and
      radiologic staging, imaging of cervical pathology, imaging of endometrial
      pathology, and imaging of mullerian duct anomalies. Foreword.

PMID- 19179858
TI  - Imaging of acute pelvic pain.
AB  - Determining the cause of acute pelvic pain in the female patient is often a
      clinical challenge. Diagnostic imaging can be invaluable in this situation.
      Ectopic pregnancy, pelvic inflammatory disease, and hemorrhagic ovarian cysts are
      the most commonly diagnosed gynecologic conditions presenting with acute pelvic
      pain. Ovarian torsion and degenerating fibroids occur less frequently. Other
      causes to consider include endometriosis, and postpartum causes such as
      endometritis, or ovarian vein thrombosis. Finally, nongynecologic conditions may
      overlap in their presentation of acute pelvic pain and should also be considered.
      The most important of these is acute appendicitis.

PMID- 19179859
TI  - Imaging of benign adnexal masses: characteristic presentations on ultrasound,
      computed tomography, and magnetic resonance imaging.
AB  - Adnexal masses are common in the general population. Although ovarian cancer is a
      significant cause of mortality, large screening studies demonstrate that the
      majority of adnexal masses are benign. These benign masses include physiologic
      cysts, paraovarian masses, and benign ovarian lesions. It is important that
      gynecologists and radiologists appreciate the appearance of these lesions on
      multiple imaging modalities, including ultrasound, computed tomography, and
      magnetic resonance imaging to avoid unnecessary intervention.

PMID- 19179860
TI  - Imaging of Mullerian duct anomalies.
AB  - Mullerian duct anomalies (MDAs) are relatively common disorders that are
      particularly relevant in patients with infertility, recurrent pregnancy loss, or
      a history of preterm labor. Accurate characterization of MDAs is crucial to the
      implementation of appropriate treatment. Various imaging modalities have been
      used in the evaluation of MDAs, including hysterosalpingography, ultrasound, and
      magnetic resonance imaging (MRI). Although hysterosalpingography and ultrasound
      may suggest a Mullerian duct anomaly, further evaluation by MRI is often
      required. MRI is the best imaging method available because of its superior
      ability to reliably visualize complex uterovaginal anatomy.

PMID- 19179861
TI  - Imaging of endometrial pathology.
AB  - The normal endometrium changes regularly with the menstrual cycle and atrophies
      after menopause. It is important to be aware of the normal spectrum of
      endometrial appearances at imaging to accurately detect and diagnose pathologic
      conditions. This article reviews imaging features of the normal and abnormal
      endometrium, and conditions which may mimic endometrial pathology. Emphasis will
      be on ultrasound with sonohysterography and magnetic resonance imaging as these
      are the imaging modalities of choice for evaluation of the endometrium. The
      complementary role of hysterosalpingography, computed tomography, and 18
      fluorodeoxyglucose-positron emission tomography will also be discussed.

PMID- 19179862
TI  - Ovarian cancer: detection and radiologic staging.
AB  - Ovarian cancer is the second most common gynecologic malignancy. It is the
      deadliest, largely owing to late stage at the time of diagnosis. Ultrasound is
      modality of choice in the evaluation of suspected adnexal masses. Magnetic
      resonance imaging is an excellent problem solver when an adnexal mass is
      indeterminate on ultrasound. Staging of ovarian cancer remains surgical, though
      preoperative imaging can identify inoperable patients and identify suspicious
      sites for intraoperative biopsy. This article reviews the use of different
      imaging modalities in the detection and staging of ovarian carcinoma, and
      discusses imaging indications, radiologic features, and the shortcomings of
      imaging.

PMID- 19179863
TI  - Imaging of cervical pathology.
AB  - A variety of benign and malignant entities affect the uterine cervix. These are
      discussed and illustrated. Cross-sectional and functional imaging can improve the
      accuracy of traditional clinical cervical cancer staging. Emphasis is placed on
      magnetic resonance imaging for initial staging and fused positron emission
      tomography-computed tomography for restaging and surveillance. The imaging
      appearance of benign cervical pathology is reviewed with ultrasonography as the
      first-line imaging modality and magnetic resonance imaging for problem solving in
      difficult cases.

PMID- 19179866
TI  - Inhalational therapies for the ICU.
AB  - PURPOSE OF REVIEW: Although drug therapy is most commonly delivered via the
      intravenous route, novel inhaled agents have been introduced for use in the ICU.
      Additionally, drugs previously delivered intravenously are now being delivered
      via the respiratory tract in an effort to reduce systemic toxicity and maximize
      effectiveness. RECENT FINDINGS: Aerosolized antibiotics have seen increased use
      in an effort to reduce systemic effects, reduce ventilator-associated pneumonia,
      and direct high drug concentrations at the site of infection. Drug-resistant
      pneumonia has also been effectively treated with aerosolized antibiotics.
      Secretion management includes a host of devices, therapies, and drugs, but the
      evidence for these is scant. Cardiac drugs via the endotracheal route should be
      used only when intravenous access is delayed. Inhaled nitric oxide has a defined
      role in care of infants, although new indications have limited and conflicting
      data. The use of helium-oxygen mixtures provides symptom relief in a wide variety
      of scenarios associated with turbulent flow in large airways. SUMMARY: Inhaled
      nitric oxide has an established role in neonatal intensive care and a limited
      role in adult intensive care. Heliox provides symptom relief, but at present
      cannot be considered routine as a consequence of the multiple technological
      challenges. Inhaled antimicrobials appear to provide a therapeutic advantage in
      select individuals with pneumonia. Secretion management is best achieved by
      adequate humidification and as needed suctioning. The role of inhaled carbon
      monoxide in critical care holds significant promise, but is currently in early
      clinical trials.

PMID- 19179867
TI  - Pleural effusion in the mechanically ventilated patient.
AB  - PURPOSE OF REVIEW: Pleural effusions (PLEF) occur frequently in mechanically
      ventilated patients (MVP). There have been improvements in bedside diagnosis,
      quantification, and drainage techniques. Nevertheless, information on the impact
      of PLEF on heart-lung performance and pathophysiologic considerations for
      drainage in MVP is limited. RECENT FINDINGS: Only four studies on physiological
      effects of PLEF drainage in MVP were found. Variable oxygenation response is
      reported. Older work suggests that the space occupying effect of PLEF is shared
      between chest wall expansion and lung collapse. Normally, the compliant chest
      wall accepts most of it, buffering its effects on lung volume and gas exchange.
      In MVP chest wall compliance and airway pressure probably play major roles on the
      response to PLEF drainage. PLEF reduces inspiratory muscle efficiency; hence
      drainage can help in weaning. PLEF can increase heart filling and pericardial
      pressures, dissociating intrathoracic vascular pressures from preload. Tamponade
      like effects with diastolic chamber collapse and circulatory impairment that
      reverses with PLEF drainage have been reported. SUMMARY: PLEF drainage does not
      always improve oxygenation in MVP with acute respiratory failure. An assessment
      of chest wall compliance and a lung recruitment maneuver may help predict the
      response. Procedural complication risks should be considered when choosing the
      best approach.

PMID- 19179868
TI  - Sleep and critical care.
AB  - PURPOSE OF REVIEW: Sleep distortion has been studied as an independent risk
      factor for morbidity and mortality; however, this role in the ICU patients is
      unclear. These patients suffer from psychological and physiological stressors and
      significant disturbance in sleep. We conducted a systematic review of all recent
      data over the last decade to elaborate the extent and implications of sleep
      disruption in the ICU. RECENT FINDINGS: Despite adequate data proving that ICU
      patients have poor quality of sleep over the last three decades, the implications
      of the sleep distortion in this patient population remains misunderstood.
      Recently, the Whitehall cohort trial has raised interest in sleep and mortality
      and substantial data have surfaced regarding prevalence of sleep disturbance in
      the ICU. SUMMARY: This article discusses the available data on sleep disruption
      in patients in the ICU and implications with discussion of effects of ventilators
      and commonly used medications in the ICU. We will conclude with interventions to
      improve sleep in the intensive care setting.

PMID- 19179869
TI  - Weaning from ventilatory support.
AB  - PURPOSE OF REVIEW: In intubated patients, mechanical ventilation offers essential
      ventilatory support, while the respiratory system recovers from acute respiratory
      failure. Yet, invasive mechanical ventilation is associated with risks and
      complications that prolong the duration of mechanical ventilation and increase
      the risk for death. Therefore, safely weaning the patient from the ventilator as
      soon as possible is paramount. Recent randomized trials have addressed a number
      of key areas of interest. RECENT FINDINGS: Determining readiness for spontaneous
      breathing, the first step in weaning, is best achieved using liberal oxygenation
      criteria; does not require routine use of weaning predictors; and can be
      conducted, in certain patient populations, using protocols driven by respiratory
      therapists or ICU nurses. Spontaneous breathing trials can be conducted on low
      levels of pressure support, continuous positive airway pressure, or T-piece.
      Weaning failure often results from an imbalance between respiratory load and
      capacity. There is increasing appreciation that cardiac dysfunction can limit
      weaning. Recent randomized trials suggest that noninvasive ventilation (in
      patients with chronic obstructive pulmonary disease) and computer-driven
      approaches show promise as weaning strategies. New techniques have been employed
      to identify patients at increased risk for extubation failure. Noninvasive
      ventilation, when used in high-risk patients, can decrease extubation failure.
      SUMMARY: Weaning from mechanical ventilation continues to be an area of
      considerable importance. Recent randomized controlled trials provide high-level
      evidence for the best approaches to weaning and extubation.

PMID- 19179870
TI  - Extracorporeal gas exchange.
AB  - PURPOSE OF REVIEW: We report on recent advances and achievements on the use of
      extracorporeal gas exchange for long-term application in the therapy of
      critically ill patients with various forms of respiratory failure. RECENT
      FINDINGS: The most important results regarding the use of extracorporeal gas
      exchange are expected from the Conventional Ventilatory Support vs.
      Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR)
      study, a randomized clinical trial assessing the effectiveness of extracorporeal
      lung assist in acute respiratory distress syndrome patients. Although not yet
      formally published, the results of this study, if confirmed, represent the first
      positive randomized clinical trial on adult extracorporeal membrane oxygenation
      application in acute respiratory distress syndrome patients. Other important
      results come from the clinical application of interventional lung assist, a
      pumpless arteriovenous extracorporeal technique, in different clinical conditions
      (acute respiratory distress syndrome, bridge to transplantation, asthma, and
      trauma). Among technical progress, of particular interest is the development of
      microfiber, microporous polymethylpentene membrane lungs, which offer low
      resistance to blood flow, high gas transfer capability, and high leak-proof
      performance. SUMMARY: Results of recent clinical trials, widespread use of
      clinical applications, and technical progress are leading to reevaluation and
      extension of extracorporeal gas exchange in critically ill patients with
      respiratory failure of various forms. Further developments may come from low
      invasive techniques with high efficiency of CO2 removal from low blood flow.

PMID- 19179871
TI  - Current Opinion in Critical Care. Current world literature.

PMID- 19179873
TI  - Intestinal lymphangiectasia.

PMID- 19179874
TI  - Clinical evidence for immunomodulatory effects of probiotic bacteria.
AB  - Close, tightly orchestrated interactions between the intestinal epithelium and
      the mucosa-associated immune system are critical for normal intestinal absorptive
      and immunological functions. Recent data indicate that commensal intestinal
      microbiota represents a major modulator of intestinal homeostasis. This review
      analyzes the process of intestinal colonization and the interaction of microbiota
      with the intestinal epithelium and mucosal immune system, with special reference
      to the first years of extrauterine life. Dysregulation of the symbiotic
      interaction between intestinal microbiota and the mucosa may result in a
      pathological condition with potential clinical repercussions. Based on the
      concept that there is a beneficial and symbiotic relation between the host and
      endogenous microbiota, strategies aimed at directly modulating intestinal
      microbiota with regard to disease prevention or treatment have been developed.
      One strategy involves administering viable probiotic bacteria. Clinical evidence
      for the beneficial effect of probiotics in the prevention and/or treatment of
      necrotizing enterocolitis, infectious and antibiotic-associated diarrhea,
      allergic diseases, and inflammatory bowel disorders is reviewed herein.

PMID- 19179875
TI  - Role of the innate immune system in the pathogenesis of inflammatory bowel
      disease.
AB  - Crohn disease and ulcerative colitis are chronic inflammatory diseases of the
      intestinal tract commonly denoted as inflammatory bowel diseases. It has been
      proposed that these diseases result from aberrant mucosal immune responses to
      nonpathogenic microbial residents of the intestines. Recently, it was established
      that continuous interactions between the innate and the adaptive intestinal
      immune cells and the microbiota are directly involved in maintaining the
      physiological noninflammatory state of the intestinal mucosa. In light of the
      complexity of this mucosal homeostasis, it is astonishing that the inflammatory
      bowel diseases are relatively rare. Recently, altered functions of the innate
      immune system have been identified. As such, both hyperresponsiveness and
      hyporesponsiveness of innate cells have been implicated in the pathogenesis of
      inflammatory bowel diseases.

PMID- 19179876
TI  - Dissociation between symptoms and histological severity in pediatric eosinophilic
      esophagitis.
AB  - OBJECTIVES: The relation between patient symptoms and histological severity of
      eosinophilic esophagitis (EE) is not known. We created a pediatric EE symptom
      score (PEESS) and compared the results with histological findings in the
      esophagus. PATIENTS AND METHODS: Subjects ages 3 to 18 years with a histological
      diagnosis of EE or their parent completed a survey rating the frequency and
      severity of their gastrointestinal symptoms. Scores ranged from 0 to 98.
      Eosinophil numbers in esophageal biopsy specimens were correlated with the PEESS.
      RESULTS: A total of 49 subjects completed the PEESS. The symptom score did not
      correlate with the peak eosinophil count (r = 0.079). Newly diagnosed, untreated
      EE subjects (N = 15) had a mean score of 24.7 +/- 16.4 with a modest correlation
      between the PEESS and the number of eosinophils in the distal esophagus (r =
      0.37). The mean PEESS score in the 34 treated patients was lower than in
      untreated patients (15.6 +/- 12.9; P = 0.046). The mean score for treated
      patients in histological remission was the same as for treated patients with
      active EE, regardless of treatment type. Abdominal pain was the most frequent and
      severe symptom reported. Among 20 of the 34 subjects (58.8%) in histological
      remission, 17 (85%) continued to report symptoms with a mean score of 17.4 +/-
      9.9 (range 1-38). Three children with active histological EE (10%) reported no
      symptoms. CONCLUSIONS: Children with untreated EE had a higher PEESS than treated
      subjects. Symptoms persisted in 85% of EE patients despite histological
      resolution and 10% with active EE reported no symptoms. Our data indicate a
      dissociation between symptoms and histology in pediatric EE.

PMID- 19179877
TI  - Anti-Saccharomyces cerevisiae antibodies status is associated with oral
      involvement and disease severity in Crohn disease.
AB  - OBJECTIVES: To determine anti-Saccharomyces cerevisiae antibodies (ASCA) status
      and its relation to disease phenotype in patients with inflammatory bowel disease
      (IBD). PATIENTS AND METHODS: A total of 301 Scottish patients with early-onset
      IBD-197 Crohn disease (CD), 76 ulcerative colitis (UC), 28 indeterminate colitis
      (IC)-and 78 healthy control individuals were studied. ASCA status (IgA, IgG) was
      determined by enzyme-linked immunosorbent assay. ASCA status was then analyzed in
      relation to CD phenotype. RESULTS: Patients with CD had a higher prevalence of
      ASCA than patients with UC and healthy controls: 82/197 versus 12/76, odds ratio
      (OR) 3.80 (1.93-7.50) and 82/197 versus 6/78, OR 8.56 (3.55-20.62), respectively.
      Univariate analysis showed that positive ASCA status was associated with oral CD
      (17/25 vs 59/153, OR 3.39 [1.38-8.34]), perianal CD (39/77 vs 38/108, OR 1.89
      [1.04-3.44]) and the presence of granulomata (63/132 vs 15/52, OR 2.25 [1.13
      4.48]) and also with markers of disease severity: raised C-reactive protein
      (44/90 vs 12/49, OR 2.95[1.36-6.37]), hypoalbuminemia (44/85 vs 20/74, OR
      2.28[1.19-4.37]), and surgery (27/49 vs 54/147, OR 2.11 [1.10-4.06]). From
      multivariate analysis, the presence of oral disease (adjusted P = 0.001, OR 22.22
      [3.41-142.86]) and hypoalbuminemia (adjusted P = 0.01, OR 4.78 [1.40-16.39]) was
      found to be independently associated with ASCA status. No association was
      demonstrated between ASCA and IBD candidate genes. CONCLUSIONS: Patients with CD
      had a higher prevalence of ASCA than did other patients with IBD. ASCA status
      described patients with CD who had a specific phenotype, showing an association
      with markers of disease severity and oral CD involvement.

PMID- 19179879
TI  - Bone mineral content deficits of the spine and whole body in children at time of
      diagnosis with celiac disease.
AB  - BACKGROUND: The aim of this study was to determine whether children with celiac
      disease (CD) have deficits in spine (SP) and whole body (WB) bone mineral content
      (BMC) at time of diagnosis, and whether the deficits are related to altered
      growth and body composition. The secondary aim was to examine the effect of
      histological grade on BMC. PATIENTS AND METHODS: A retrospective study of
      children who had undergone a dual energy x-ray absorptiometry scan at the time of
      diagnosis with CD between October 1, 2003, and June 15, 2006, were compared with
      a healthy reference sample of similar age and race from the same geographic
      region in the United States. SP and WB BMC were expressed as sex-specific z
      scores relative to age and relative to height to assess differences in the CD
      group versus controls. Pearson correlation, t tests, and analysis of variance
      were performed to determine predictors of BMC. RESULTS: Forty-four children (mean
      age 10.6 +/- 3.4 years; 77% female, 96% white) with CD were evaluated and
      compared with 338 healthy children. Children with CD were shorter than children
      of similar age and sex. SP and WB BMC for age z scores were significantly lower
      in the CD group compared with controls. When adjusted for height, significant
      deficits in WB BMC persisted in patients with CD. Low SP and WB BMC correlated
      with advanced histological grade in CD. Low body mass index correlated with low
      WB BMC in CD. CONCLUSIONS: Newly diagnosed children with CD may benefit from
      screening for low bone mineral content. Patients with low body mass index and
      those with advanced histological damage (Marsh grade IIIc) particularly may be at
      risk for osteopenia.

PMID- 19179878
TI  - Growth abnormalities persist in newly diagnosed children with crohn disease
      despite current treatment paradigms.
AB  - OBJECTIVES: We analyzed growth outcomes in children newly diagnosed with Crohn
      disease and determined whether growth abnormalities persist despite current
      therapies. PATIENTS AND METHODS: Clinical and growth data were prospectively
      obtained on an inception cohort younger than 16 years old at diagnosis and Tanner
      I to III during the study. RESULTS: In all, 176 children (mean age 10.1 years;
      65% male) with mild (33%) or moderate/severe (67%) disease at diagnosis were
      studied. Disease activity at 1 year was inactive/mild (89%) or moderate/severe
      (11%). First-year treatments included immunomodulators (60%), corticosteroids
      (77%), 5-aminosalicylates (61%), infliximab (15%), and enteral nutrition (10%).
      By 2 years, 86% had received immunomodulators and 36% infliximab. Mean height z
      scores at diagnosis, 1 year, and 2 years were -0.49 +/- 1.2 standard deviations
      (SDs), -0.50 +/- 1.2, and -0.46 +/- 1.1, respectively. Of the subjects, 10%, 8%,
      and 6.5% had height z scores less than -2 SD at diagnosis, 1 year, and 2 years. A
      height velocity z score less than -1SD was seen in 45% of subjects at 1 year and
      38% at 2 years. The mean height velocity z score, however, increased between 1
      and 2 years from -0.71 to 0.26 (P < 0.03). Corticosteroid use greater than 6
      months in the first year was associated with abnormal height velocity at 1 year
      (adjusted odds ratio = 4.5; 95% confidence interval [CI] = 2.2-9.6). No
      statistically significant effect on height velocity z scores was noted when
      comparing those receiving or not receiving infliximab. CONCLUSIONS: Growth delay
      persists in many children with CD following diagnosis, despite improved disease
      activity and the frequent use of immunomodulators and biologics. Additional
      strategies to improve growth outcomes require development.

PMID- 19179880
TI  - Seasonality of birth month of children with celiac disease differs from that in
      the general population and between sexes and is linked to family history and
      environmental factors.
AB  - BACKGROUND: Patients with autoimmune diseases, such as type 1 diabetes mellitus,
      atopic dermatitis, autoimmune thyroid diseases, and multiple sclerosis have a
      different seasonality of month of birth (MOB) from the general population. This
      study was undertaken to determine the seasonality of MOB in children with celiac
      disease (CD), an autoimmune-mediated enteropathy. PATIENTS AND METHODS: The
      medical records of 431 children with CD (239 girls, 192 boys) were included in
      the study; 138 girls and 81 boys were under the age of 24 months. Data were
      analyzed by the cosinor method, which, in addition to statistical significance,
      provides parameters of rhythms. Statistical differences between groups were also
      analyzed by the chi test. RESULTS: Patients with CD showed different patterns
      from that in the general population, which peaks in September. Boys and girls
      with CD were found to have a different seasonality of MOB (P < 0.02). Girls whose
      CD was diagnosed before age 24 months (peak July-August) had a different
      seasonality of MOB from those whose CD was diagnosed after age 24 months (no
      rhythm; P < 0.005) and showed a different seasonality from boys whose CD was
      diagnosed above 24 months (peak July; P < 0.02). In addition, we found a
      different seasonality of MOB in children with a family history of CD compared
      with those with no family history (P < 0.001). CONCLUSIONS: Girls with the
      diagnosis of CD and patients of both sexes with a family history of CD have a
      different pattern of seasonality of birth from the general population. This is
      suggestive of a perinatal virus infection as a plausible candidate for the
      primary trigger.

PMID- 19179881
TI  - Evaluation and management of neonatal dysphagia: impact of pharyngoesophageal
      motility studies and multidisciplinary feeding strategy.
AB  - BACKGROUND AND OBJECTIVES: Abnormal swallowing (dysphagia) among neonates is
      commonly evaluated using the videofluoroscopic swallow study (VSS). Radiological
      findings considered high risk for administration of oral feeding include
      nasopharyngeal reflux, laryngeal penetration, aspiration, or pooling. Our aims
      were to determine pharyngoesophageal motility correlates in neonates with
      dysphagia and the impact of multidisciplinary feeding strategy. METHODS: Twenty
      dysphagic neonates (mean gestation +/- standard deviation [SD] = 30.9 +/- 4.9
      weeks; median 31.1 weeks; range = 23.7-38.6 weeks) with abnormal VSS results were
      evaluated at 49.9 +/- 16.5 weeks (median 41.36 weeks) postmenstrual age. The
      subjects underwent a swallow-integrated pharyngoesophageal motility assessment of
      basal and adaptive swallowing reflexes using a micromanometry catheter and
      pneumohydraulic water perfusion system. Based on observations during the motility
      study, multidisciplinary feeding strategies were applied and included postural
      adaptation, sensory modification, hunger manipulation, and operant conditioning
      methods. To discriminate pharyngoesophageal manometry correlates between oral
      feeders and tube feeders, data were stratified based on the primary feeding
      method at discharge, oral feeding versus tube feeding. RESULTS: At discharge, 15
      of 20 dysphagic neonates achieved oral feeding success, and the rest required
      chronic tube feeding. Pharyngoesophageal manometry correlates were significantly
      different (P < 0.05) between the primary oral feeders versus the chronic tube
      feeders for swallow frequency, swallow propagation, presence of adaptive
      peristaltic reflexes, oral feeding challenge test results, and upper esophageal
      sphincter tone. VSS results or disease characteristics had little effect on the
      feeding outcomes (P = NS). CONCLUSIONS: Swallow-integrated esophageal motility
      studies permit prolonged evaluation of swallowing reflexes and responses to
      stimuli under controlled conditions at cribside. The dysfunctional neuromotor
      mechanisms may be responsible for neonatal dysphagia or its consequences.
      Manometry may be a better predictor than VSS in identifying patients who are
      likely to succeed in vigorous intervention programs.

PMID- 19179883
TI  - High-titer antibody to hepatitis B surface antigen before liver transplantation
      can prevent de novo hepatitis B infection.
AB  - OBJECTIVE: De novo hepatitis B virus (HBV) infection is defined as infection
      occurring in HBV surface antigen (HBsAg)-negative patients who become HbsAg
      positive after organ transplantation. We assessed the incidence and risk factors
      of de novo HBV infection in pediatric liver transplant recipients. PATIENTS AND
      METHODS: From 1996 to 2006, 71 Taiwanese children with non-HBV-related liver
      diseases underwent orthotopic liver transplantation (OLT) at the National Taiwan
      University Hospital. All of the surviving recipients were tested regularly for
      liver function, serum levels of immunosuppressant, HBsAg, titers of antibodies to
      hepatitis B surface antigen (anti-HBs), antibodies to hepatitis B core antigen
      (anti-HBc), and antibodies to hepatitis C virus (anti-HCV). HBV vaccination
      histories and the anti-HBs titers before OLT were recorded. No regular
      prophylaxis was given. RESULTS: Fifty-nine patients (33 girls and 26 boys) were
      followed up for a median of 4.4 years (range 1.0-10.0). Of those, 36 (61.0%)
      received allografts from anti-HBc-positive and HBsAg-negative donors. De novo HBV
      infection was found in 9 (15.3%) patients after OLT, 8 of whom received
      allografts from HBsAg-negative and anti-HBc-positive donors. Forty-eight (81.4%)
      patients received 3 or more doses of HBV vaccine before OLT. Pre-OLT anti-HBs
      titers were available for 49 recipients. Of the 9 de novo HBV-infected
      recipients, 8 had anti-HBs titers <200 mIU/mL. No graft loss or fulminant
      hepatitis was noted. CONCLUSIONS: In the absence of adequate prophylaxis, the
      incidence of de novo HBV infection in pediatric OLT recipients is 15.3%. An anti
      HBs titer of >200 mIU/mL before OLT may be sufficient to prevent de novo HBV
      infection in HBsAg-negative recipients.

PMID- 19179882
TI  - Alteration of canalicular transporters in a mouse model of total parenteral
      nutrition.
AB  - OBJECTIVES: Parenteral nutrition-associated liver disease (PNALD) is a major
      problem with prolonged total parenteral nutrition (TPN) administration. Our
      laboratory previously demonstrated significant changes in the expression of
      multidrug resistance genes (MDRs) 1 and 2, hepatocyte transporters, in a TPN
      mouse model. The present study hypothesized that these changes would lead to
      functional changes in the liver, and would contribute to the development of liver
      dysfunction. MATERIALS AND METHODS: Mice received either intravenous saline and
      standard chow or TPN with or without intravenous lipids. Functional assays were
      performed after 7 days of infusion. RESULTS: TPN with lipids led to a significant
      increase in serum bile acid levels, consistent with an early state of PNALD. Use
      of TPN without lipids prevented an elevation in bile acid levels. In both TPN
      groups, MDR2 expression was significantly (68%) lower than controls and bile
      phosphatidylcholine content, a functional measure of MDR2, was 40% less than
      controls. MDR1 expression in the TPN with lipid group was 31% higher than
      controls, whereas in the TPN without lipids mice there was no significant change.
      Hepatocyte extrusion of rhodamine dye, a measure of MDR1 function, declined only
      in the TPN with lipid group. Peroxisome proliferator-activated receptor-alpha
      expression decreased in both TPN groups. Fenofibrate given with TPN resulted in
      an increased expression of MDR1 and MDR2, and functionally increased hepatocyte
      rhodamine extrusion and presence of bile phosphatidylcholine in the TPN with
      lipid group. CONCLUSIONS: The study shows that TPN led to alterations in the
      function of MDR1- and MDR2-expressed proteins. The changes help in the
      understanding of the mechanisms leading to PNALD, and suggest that fibrate
      administration may palliate these changes.

PMID- 19179884
TI  - Changing the paradigm: omegaven for the treatment of liver failure in pediatric
      short bowel syndrome.
AB  - BACKGROUND: Parenteral omega-3 fatty acids, such as Omegaven, may benefit
      patients with pediatric short bowel syndrome (SBS) who develop parenteral
      nutrition-associated liver disease (PNALD). PATIENTS AND METHODS: Retrospective
      cohort describing the outcome of all 12 children with SBS and advanced PNALD who
      were treated with Omegaven (target omega-6 to omega-3 fatty acid ratio = 1:1 to
      2:1). RESULTS: The median age was 7.5 (range 3.6-46) months, and median
      parenteral nutrition duration before starting Omegaven was 28.4 (range 15.3-55.3)
      weeks. Median initial serum conjugated bilirubin was 137 (range 54-203)
      micromol/L (8.06 [3.18-11.94] mg/dL). Of the 12 patients, 9 had complete and
      sustained resolution of hyperbilirubinemia within a median of 24 (range 7-37)
      weeks, and all are no longer being considered for liver transplantation.
      Improvements in markers of hepatic inflammation as well as nutritional status
      also were noted in these patients. Three patients received a liver-intestine
      transplant while taking Omegaven. There were no complications attributable to
      Omegaven. CONCLUSIONS: Omegaven is associated with restoration of liver function
      in patients with SBS and advanced liver disease. Parenteral omega-3 fatty acids,
      such as Omegaven, have the potential to fundamentally alter the paradigm of
      neonatal SBS from one of early death or transplantation from liver failure to a
      more chronic disease. More children with SBS should achieve full enteral
      tolerance and those who do not have the capacity for intestinal adaptation should
      be able to survive and receive an intestinal graft when older.

PMID- 19179886
TI  - Secondary malnutrition and overweight in a pediatric referral hospital:
      associated factors.
AB  - OBJECTIVES: To establish the prevalence and identify the clinical and
      sociodemographic factors associated with malnutrition and overweight in a
      pediatric referral hospital. PATIENTS AND METHODS: We studied a cross-sectional,
      random sample from a pediatric hospital. Malnutrition was defined as acute when
      the z score of weight/height was less than -2.0 and as chronic if in addition the
      height/age z score was less than -2.0. Overweight risk was defined as a body mass
      index percentile between 85 and 94, and overweight as a body mass index
      percentile of 95 or higher. RESULTS: The study included 641 patients, with mean
      age 7.1 +/- 4.9 years (56% male). The overall prevalence of acute malnutrition
      was 8% and chronic malnutrition 17.0%. Overweight risk was present in 15.4% and
      overweight in 12.2%. Acute malnutrition was predicted by conditions on admission
      (hospitalization: odds ratio [OR] 2.3, confidence interval [CI] 1.3-4.3;
      nonsurgical subspecialty: OR 2.1, CI 1.0-4.3) and number of siblings (1 child,
      single mother: OR 2.6, CI 1.3-5.0). Chronic malnutrition was predicted by age
      (infants vs preschoolers: OR 2.0, CI 1.1-3.6; infants vs school children: OR 3.1,
      CI 1.8-5.5) and illness duration (>30 days: OR 2, CI 1.1-3.7). Overweight risk
      was associated with age (>36 months: OR 2.0, CI 1.6-3.4) and the father's
      educational level (college and university: OR 2.3, CI 1.3-4.3). Overweight was
      predicted by sex (boys: OR 2.0, CI 1.0-3.6) and age (>36 months: OR 1.7, CI 1.0
      2.8). CONCLUSIONS: Overweight was as prevalent as malnutrition. Malnutrition was
      associated with clinical condition, age, family size, and illness duration,
      whereas overweight was related to age, sex, and father's education. Overweight
      appears as a novel finding in the nutritional profile of pediatric referral
      hospitals in Mexico.

PMID- 19179887
TI  - Complicated diverticular disease in a child with williams syndrome.

PMID- 19179885
TI  - A randomized placebo-controlled comparison of 2 prebiotic/probiotic combinations
      in preterm infants: impact on weight gain, intestinal microbiota, and fecal short
      chain fatty acids.
AB  - OBJECTIVE: To compare the effect of 2 prebiotic/probiotic products on weight
      gain, stool microbiota, and stool short-chain fatty acid (SCFA) content of
      premature infants. PATIENTS AND METHODS: This randomized, blinded, placebo
      controlled trial included 90 premature infants treated with either a dietary
      supplement containing 2 lactobacillus species plus fructooligosaccharides (CUL,
      Culturelle, ConAgra, Omaha, NE), a supplement containing several species of
      lactobacilli and bifidobacteria plus fructooligosaccharides (PBP, ProBioPlus DDS,
      UAS Laboratories, Eden Prairie, MN), or placebo (a dilute preparation of
      Pregestamil formula) twice daily for 28 days or until discharge if earlier. The
      primary outcome was weight gain. Secondary outcomes were stool bacterial analysis
      by culture and 16S rDNA quantitative polymerase chain reaction and stool SCFA
      content measured by high performance liquid chromatography. RESULTS: Both
      prebiotic/probiotic combinations contained more bacterial species than noted on
      the label. No significant effect on infant growth of either prebiotic/probiotic
      supplement was observed. By cultures, 64% of infants receiving PBP became
      colonized with bifidobacteria, compared with 18% of infants receiving CUL and 27%
      of infants receiving placebo (chi-square, P = 0.064). No differences were noted
      between groups in colonization rates for lactobacilli, Gram-negative enteric
      bacteria, or staphylococci. By 16S rDNA polymerase chain reaction analysis, the
      bifidobacteria content in the stools of the infants receiving PBP was higher than
      in the infants receiving CUL or placebo (Kruskal-Wallis, P = 0.011). No
      significant differences in stool SCFA content were detected between groups. No
      adverse reactions were noted. CONCLUSIONS: Infants receiving PBP were more likely
      to become colonized with bifidobacteria. No significant differences in weight
      gain or stool SCFA content were detected.

PMID- 19179888
TI  - Gastric Burkitt lymphoma: A rare cause of upper gastrointestinal bleeding in a
      child with HIV/AIDS.

PMID- 19179889
TI  - A histone deacetylase inhibitor LBH589 downregulates XIAP in mesothelioma cell
      lines which is likely responsible for increased apoptosis with TRAIL.
AB  - PURPOSE: Tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) is
      a member of tumor necrosis factor family and it is important for ligand induced
      apoptosis in tumor cells. TRAIL has been shown to be synergistic with a variety
      of chemotherapies and targeted agents. In the study, a combination of TRAIL and a
      histone deacetylase inhibitor LBH589 was studied in mesothelioma cell lines.
      EXPERIMENTAL DESIGN: Five mesothelioma cell lines and two normal cell lines were
      tested for cell growth inhibition and apoptosis using high-throughput assays in
      the presence of LBH589, TRAIL and a combination of the two. Caspase induction was
      studied and levels of X-linked inhibitor of apoptosis (XIAP) were tested using
      Western blotting. A combination of a direct inhibitor of XIAP was also tested in
      combination with TRAIL. RESULTS: In mesothelioma cell lines, a combination of
      LBH589 and TRAIL markedly increased cell growth inhibition and apoptosis when
      compared with the effect on normal cell lines. LBH589 and TRAIL appeared to
      induce higher levels of caspase 3 and 7 and this appeared to be closely related
      to ability of LBH589 to degrade XIAP. In addition, a direct inhibitor of XIAP was
      also sensitized cells to TRAIL apoptosis, providing an indirect confirmation for
      XIAP degradation as a possible mechanism of synergy. CONCLUSIONS: In mesothelioma
      cell lines, LBH589 increases the sensitivity to TRAIL. In addition, at least
      partly, the mechanism of this induction of TRAIL sensitivity is due to LBH589
      related degradation of XIAP. These results provide initial evidence for testing
      this combination in clinical trials.

PMID- 19179891
TI  - A Bayesian model for age, period, and cohort effects on mortality trends for lung
      cancer, in association with gender-specific incidence and case-fatality rates.
AB  - INTRODUCTION: To study time trends in lung cancer mortality by separating the
      incidence and case-fatality rates, in association with age, period, and cohort
      effects. METHODS: Lung cancer cases (n = 44,139) diagnosed between 1996 and 2002
      in Taiwan were analyzed by decomposing the time trend in mortality into incidence
      and case-fatality rates. Descriptive data, together with periodical treatment
      distribution (surgery, chemotherapy, and others) were analyzed using a Bayesian
      age, period, and cohort (BAPC) model. RESULTS: Midterm mortality (2-year age
      adjusted standardized mortality rate) has been decreasing for male lung cancer
      patients since about 2000, mainly because of a decrease in incidence during this
      period. For women, 2-year age-adjusted standardized mortality rate has been
      slightly increasing, mainly as a result of increasing incidence. There were small
      improvements (3-6%) in the short-term (1-year) case-fatality rate, possibly owing
      to increased utilization (approximately 15-18%) of chemotherapy. The midterm (2
      year) case-fatality rate remained roughly the same, especially for men.
      CONCLUSIONS: Using a new BAPC model, we found that the trends in mortality for
      lung cancer paralleled the changes in incidence, with opposite effects in men and
      women. Increased utilization of chemotherapy might have partly accounted for the
      small improvement in the case-fatality rate. The contributions of other
      unmeasured factors such as staging and histologic distribution remain to be
      clarified in future studies.

PMID- 19179890
TI  - Histone deacetylase inhibitor romidepsin enhances anti-tumor effect of erlotinib
      in non-small cell lung cancer (NSCLC) cell lines.
AB  - INTRODUCTION: Most epidermal growth factor receptor (EGFR) mutant non-small cell
      lung cancers (NSCLCs) are sensitive to EGFR tyrosine kinase inhibitors (TKIs)
      such as erlotinib or gefitinib, but many EGFR wild type NSCLCs are resistant to
      TKIs. In this study, we examined the effects of the histone deacetylase
      inhibitor, romidepsin, in combination with erlotinib, in NSCLC cell lines and
      xenografts. METHODS: For in vitro studies, nine NSCLC cell lines with varying
      mutation status and histology were treated with erlotinib and romidepsin alone or
      in combination. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium assays were performed to determine the concentration
      that inhibits 50% (IC50) value of each drug or the combination. For in vivo
      studies, NCI-H1299 xenografts were inoculated subcutaneously into athymic nude
      mice. Romidepsin and/or erlotinib were injected intraperitoneally after tumors
      developed and tumor sizes were measured. RESULTS: We found that romidepsin
      increased the sensitivity of erlotinib synergistically in all nine NSCLC cell
      lines including EGFR and KRAS wild type cell lines, KRAS mutant cell lines, and
      TKI resistant EGFR mutant cell lines. This effect was partially due to enhanced
      apoptosis. Furthermore, cotreatment of erlotinib and romidepsin inhibited NCI
      H1299 xenograft growth in athymic nude mice. CONCLUSIONS: These observations
      support a role for the combination of a histone deacetylase inhibitor and a TKI
      in the treatment of NSCLCs.

PMID- 19179892
TI  - Elevated levels of oxidative stress markers in exhaled breath condensate.
AB  - INTRODUCTION: Lung cancer is the leading cause of cancer death and oxidative
      stress secondary to carcinogens such as cigarette smoke has been implicated in
      its pathogenesis. Therefore, lung cancer patients were hypothesized to have
      higher levels of oxidative stress markers in their exhaled breath compared with
      controls. METHODS: Exhaled breath condensate (EBC) was collected from newly
      diagnosed subjects with non-small cell lung cancer (NSCLC) and control subjects
      in a cross-sectional observational study. The samples were then analyzed for
      hydrogen peroxide (H(2)O(2)), pH, 8-isoprostane, and antioxidant capacity.
      RESULTS: A total of 71 subjects (21 NSCLC patients, 21 nonsmokers, 13 exsmokers,
      and 16 smokers) were recruited. NSCLC patients had significantly higher EBC
      H(2)O(2) concentration (NSCLC subjects versus smokers, 10.28 microM, 95%
      confidence interval [CI]: 4.74-22.30 and 2.29 microM, 95% CI: 1.23-4.25,
      respectively, p = 0.003) and lower antioxidant capacity (NSCLC versus smokers,
      0.051 mM, 95% CI: 0.042-0.063 and 0.110 mM, 95% CI: 0.059-0.206, p = 0.023; NSCLC
      versus all controls as a group, 0.051 mM, 95% CI: 0.042-0.063 and 0.087 mM, 95%
      CI: 0.067-0.112, p = 0.001). They also had significantly lower pH (5.9, 3.3-7.3)
      compared with exsmokers (6.7, 5.8-7, p = 0.009). CONCLUSION: The significant
      increase of H(2)O(2) and reduction in antioxidant capacity in the EBC of lung
      cancer patients further support the concept of the disequilibrium between levels
      of oxidants and antioxidants in lung cancer, which leads to increased oxidative
      stress. These findings suggest oxidative stress is implicated in the development
      of lung cancer and may be an early marker of the disease.

PMID- 19179893
TI  - Patterns of cardiac perfusion abnormalities after chemoradiotherapy in patients
      with lung cancer.
AB  - OBJECTIVE: We evaluated the prevalence of myocardial perfusion defects using
      myocardial perfusion imaging (MPI) after chemoradiation or radiation therapy
      (CRT/RT) in lung cancer patients and described their patterns in relation to
      tumor location. METHODS: MPI in 44 patients who received RT for lung cancer and
      44 control patients were compared. The two groups were comparable in risk factors
      for coronary artery disease. Data regarding tumor stage and location, interval
      between CRT/RT and MPI, and mean radiation dose to the heart was collected. The
      level of radiation delivered to the affected segments of the left ventricle
      versus the normal segments was compared using the isodose lines on the simulation
      computed tomography. RESULTS: Considering all tumor locations, 8 patients (18%)
      demonstrated MPI defects after CRT/RT versus 9 (20%) in the controls. However, 7
      of 18 patients (39%) with centrally located tumors in the CRT/RT group versus
      only 1 of 15 patients (7%) in the control group demonstrated MPI defect (p=
      0.04). The defects in the CRT/RT group were in the anterior and septal segments
      while the defects were in different segments in the controls. The median interval
      between end of RT and MPI was 12.3 months. The affected segments in the CRT/RT
      group received a mean radiation dose of 39.6 versus 11.4 Gy (p = 0.003) to the
      normal segments. CONCLUSIONS: CRT/RT to centrally located lung tumors tends to
      cause anterior/septal MPI defects. Abnormal MPI segments in the CRT/RT group have
      received significantly higher radiation than normal segments.

PMID- 19179894
TI  - Surgical treatment and prognosis of primitive neuroectodermal tumors of the
      thorax.
AB  - INTRODUCTION: Primitive neuroectodermal tumors (PNETs) are rare, rapidly
      progressive, small- round cell tumors with a poor prognosis despite multimodal
      therapy, including surgery and chemoradiotherapy. The treatment of choice was
      unknown since no clinical series with surgical therapy had been reported. We
      evaluated the impact of multimodal treatment in patients with PNETs located in
      the thoracic region. METHODS: Between 1998 and 2006, 25 patients with PNETs in
      the thoracic region were treated in 3 tertiary-care hospitals. The patients
      consisted of 15 males and 10 females with a mean age of 27.2 years (range, 6-60).
      The tumor was in the chest wall in 20 (involving the costovertebral junction in
      9), the lung in four, and the heart in one patient. Twelve patients received
      neoadjuvant chemotherapy (54.5%), and 22 of 25 patients underwent surgery.
      RESULTS: In patients who received neoadjuvant treatment, the mean regression rate
      was 65.4% (range, 30-100%). Eighteen (82%) patients underwent chest wall
      resection, while 7 (32%) had vertebral resections, and the remaining 4 (16%) had
      pulmonary resections. A complete resection was possible in 18 of 22 patients
      (82%). Patients with incomplete and complete resections had 25% and 56% 5-year
      survival rates, respectively (p = 0.13). The progression-free 3-year survival
      rate was 36% and the median survival time was 13 months. The complete resection
      rate was significantly higher in patients receiving neoadjuvant therapy (p =
      0.027). The 5-year survival rate of the patients with or without neoadjuvant
      therapy was 77% and 37%, respectively (p = 0.22) although it prolonged the
      disease-free survival (p = 0.01). The 5-year survival rate of patients without
      costovertebral junction involvement was 66%, whereas patients with PNETs
      involving the costovertebral junction had a 21% 3-year survival. The difference
      was statistically significant (p = 0.01). The 5-year progression-free survival
      rate of patients without costovertebral junction involvement was 58%, whereas
      patients with PNETs involving the costovertebral junction had a 14% 1-year
      progression-free survival (p = 0.004). CONCLUSIONS: PNET is an aggressive
      malignancy that often requires multimodal therapy. Induction chemotherapy leads
      to a greater complete resection rate and better disease-free survival, while
      involvement of the costovertebral junction indicates a poorer survival.

PMID- 19179895
TI  - The perioperative complications for elderly patients with lung cancer associated
      with a pulmonary resection under general anesthesia.
AB  - BACKGROUND: Surgery for elderly patients with lung cancer is relatively common
      due to the increasing elderly population. This study evaluated the perioperative
      complications associated with surgery in patients over 70 years of age with lung
      cancer. PATIENTS AND METHODS: A single-center retrospective evaluation was
      conducted of perioperative complications (1996-2006) in lung cancer surgical
      patients. We reviewed and analyzed the clinical records of 364 consecutive
      patients over 70 years of age and 392 control patients. RESULTS: The mean age of
      the elderly group was 75.5 years old and that of the control group was 59.4
      years. A segmental or wedge resection was performed more frequently for the
      elderly group than in the control group, whereas pneumonectomies and lobectomies
      were performed more frequently in the control group. Preoperative comorbidities
      such as cardiac and thoracic diseases were more frequently recognized in the
      elderly group than in the control group. The quantity of propofol used as
      induction anesthesia in the elderly group was significantly smaller than that of
      the control group, furthermore, the operation time and operation room stay time
      of the elderly group were significantly shorter than that of the control group,
      however, extubation time was significantly prolonged. The ratio of thoracic
      complications in the elderly group was higher than that in the control group. The
      ratio of pulmonary leakage in the elderly group was higher than in the control
      group; however, there was no significant difference in length of stay in the
      hospital, the ratio of operative death and hospital death between the two groups.
      CONCLUSIONS: Elderly patients more frequently have perioperative complications
      than younger patients; however, there was no statistical difference in mortality.
      A pulmonary resection for elderly patients may therefore be as feasible as in
      younger patients.

PMID- 19179896
TI  - Intraoperative sentinel node mapping with technitium-99 in lung cancer: results
      of CALGB 140203 multicenter phase II trial.
AB  - INTRODUCTION: Sentinel node mapping with radioactive technetium in non-small cell
      lung cancer has been shown to be feasible in several single institution reports.
      The Cancer and Leukemia Group B designed a phase II trial to test a standardized
      method of this technique in a multi-institutional setting. If validated, the
      technique could provide a more accurate and sensitive way to identify lymph node
      metastases. METHODS: Patients with clinical stage I non-small cell lung cancer
      amenable to resection were candidates for this trial. Intraoperatively, tumors
      were injected with technetium sulfur colloid (0.25 mCi). The tumor and lymph
      nodes were measured in vivo with a hand held Geiger counter and resection of the
      tumor and nodes was carried out. Sentinel nodes, all other nodes and the tumor
      were analyzed with standard histologic assessment. Negative sentinel nodes were
      also evaluated with immunohistochemistry. RESULTS: In this phase II trial, 8
      surgeons participated (1-13 patients enrolled per surgeon), and 46 patients (out
      of a planned 150) were enrolled. Of these, 43 patients had cancer and an
      attempted complete resection, and 39 patients underwent sentinel node mapping.
      One or more sentinel nodes were identified in 24 of the 39 patients (61.5%). The
      sentinel node(s) were found to be accurate (no other nodes were positive for
      cancer if the sentinel node was negative) in 20/24 patients (83.3%). In the
      overall group the sentinel node mapping procedure was found to be accurate in
      20/39 patients (51.2%). CONCLUSIONS: Intraoperative sentinel node mapping in lung
      cancer with radioisotope yielded lower accrual and worse accuracy than expected.
      The multi-institutional attempt at validating this technique was unsuccessful.

PMID- 19179897
TI  - Resection of pulmonary metastasis of non-small cell lung cancer.
AB  - INTRODUCTION: Management of pulmonary metastasis of non-small cell lung cancer
      (NSCLC) remains controversial. We reviewed our surgical treatment for pulmonary
      metastasis of NSCLC. METHODS: Seventy-six patients with pulmonary metastasis of
      NSCLC underwent pulmonary resections in two institutes during the past 10 years.
      Eighteen patients with simultaneous same lobe metastasis as the primary lesion
      underwent mostly lobectomies. Sixteen patients with simultaneous different lobe
      metastasis underwent combined margin-free resections. Forty-nine pulmonary
      metastasectomies were performed in 42 patients with recurrent lung cancer.
      Overall survival and disease-free survival in each group were examined, and
      factors affecting survivals were investigated. RESULTS: In the patients with the
      same lobe metastasis 5-year survival was 79.6%, and median and 5-year disease
      free survivals were 39.1 months and 41.3%. In the patients with simultaneous
      different lobe metastasis median survival and 5-year survival were 37.7 months
      and 30.7%, and median and 5-year disease-free survivals were 13.3 months and
      12.5%, respectively. Multiple pulmonary metastasis and mediastinal node
      metastasis were identified as significant factors affecting survivals. In the
      patients with recurrent pulmonary metastasis median survival and 5-year survival
      were 40.0 months and 34.8%, and median and 5-year disease-free survivals were
      23.7 months and 14.4%, respectively. Node metastasis, higher age, and shorter
      interval from the prior resection were identified as significant factors
      affecting survivals. CONCLUSIONS: These findings suggest that the simultaneous
      same lobe metastasis is under the same indication for the primary lesion, and
      that the simultaneous different lobe metastasis and recurrent pulmonary
      metastasis should be removed in selected patients.

PMID- 19179898
TI  - Circulating endothelial cells in non-small cell lung cancer patients treated with
      carboplatin and paclitaxel.
AB  - INTRODUCTION: Circulating endothelial cells (CECs) increase in cancer patients
      and play an important role in tumor neovascularization. METHODS: This study was
      designed to investigate the role of CEC as a marker for predicting the
      effectiveness of a carboplatin plus paclitaxel based first line chemotherapy in
      advanced non-small cell lung cancer (NSCLC). RESULTS: The CEC count in 4 ml of
      peripheral blood before starting chemotherapy (baseline value) was significantly
      higher in NSCLC patients, ranging from 32 to 4501/4 ml (n = 31, mean +/- SD = 595
      +/- 832), than in healthy volunteers (n = 53, 46.2 +/- 86.3). We did not detect a
      significant correlation between the CEC count and estimated tumor volume. CECs
      were significantly decreased by chemotherapy as compared with pretreatment values
      (175.6 +/- 24 and 173.0 +/- 24, day +8, +22, respectively). We investigated the
      correlation between baseline CEC and the clinical effectiveness of chemotherapy.
      CEC values are significantly higher in patients with clinical benefit (partial
      response and stable disease, 516 +/- 458, 870.8 +/- 1215, respectively) than in
      progressive disease patients (211 +/- 150). Furthermore, a statistically
      significant decrease in CECs, on day 22, was observed only in patients with
      partial response. Patients who had a baseline CEC count greater than 400/4 ml
      showed a longer progression-free survival (>400, 271 days [range: 181-361] versus
      <400, 34 [range: 81-186], p = 0.019). CONCLUSION: CEC is suggested to be a
      promising predictive marker of the clinical efficacy of the CBDCA plus paclitaxel
      regimen in patients with NSCLC.

PMID- 19179899
TI  - A phase II study of erlotinib as initial treatment for patients with stage IIIB
      IV non-small cell lung cancer.
AB  - INTRODUCTION: Erlotinib improves survival in patients with advanced non-small
      cell lung cancer who have been previously treated with systemic chemotherapy. The
      current trial was designed to evaluate erlotinib as a primary therapy before
      chemotherapy in patients with minimally restricted eligibility criteria. METHODS:
      Eligibility criteria included stage IIIB/IV or recurrent non-small cell lung
      cancer, no prior chemotherapy for systemic disease, performance status = 0 to 1,
      no history of brain metastases, and weight loss less than 10%. Patients received
      erlotinib 150 mg/d until objective or symptomatic progression when they were
      offered conventional chemotherapy. The primary end point was progression-free
      survival. RESULTS: Forty patients were accrued. The median age was 65 years, 35
      had performance status = 1, 8 were never-smoker, and 23 were former smokers.
      Histologies were adenocarcinoma in 22 and squamous cell in six. The major
      toxicity was rash (grade 1, 12; grade 2, 16; grade 3, 3). Partial responses were
      observed in six (15%), stable in 11 (28%), and progressive disease in 23 (58%).
      The median time on erlotinib was 8 weeks. The median survival was 50 weeks with
      1, 2, and 3 years survivals of 44%, 18%, and 16%. Retrospective epidermal growth
      factor receptor mutational analysis was performed in 18 subjects and four
      mutations (22%) were identified. Only 25 patients have received subsequent
      chemotherapy (too early, 4; refused, 9; and unable because of performance status,
      2), and, of these, 9 (36%) achieved unconfirmed responses. CONCLUSIONS: Despite a
      modest response rate, lack of enrichment for never-smokers and absence of
      conventional chemotherapy in many patients, the median and long-term survivals
      were comparable with those expected after conventional sequencing of
      chemotherapy. Erlotinib as initial therapy was well tolerated and warrants
      randomized evaluation as first-line treatment for advanced lung cancer.

PMID- 19179900
TI  - A phase II study of carboplatin, etoposide, and exisulind in patients with
      extensive small cell lung cancer: CALGB 30104.
AB  - PURPOSE: To assess the efficacy and toxicity of carboplatin, etoposide, and
      exisulind as initial therapy for extensive stage small cell lung cancer. PATIENTS
      AND METHODS: The Cancer and Leukemia Group B conducted a phase II study of
      carboplatin (area under the curve 6) day 1 and etoposide 80 mg/m(2) days 1-3
      administered intravenously every 21 days with exisulind 250 mg orally twice daily
      in 44 evaluable patients with previously untreated extensive stage small cell
      lung cancer. The hypothesis was the addition of a novel cytostatic agent to
      standard therapy may increase survival time. The primary end point of the study
      was to evaluate overall survival. The secondary end points were to characterize
      response rates and toxicity. RESULTS: The majority of the patients were male
      (64%), Caucasian (95%), and had performance status 0 or 1 (77%). The median age
      was 61 (range 44-82) years. The percentage of patients alive at 1 year was 36.4%
      (95% [confidence interval] CI: 24.6-53.8%). The median overall survival was 10.6
      months (95% CI: 9.1-14.7). The best overall response rate was 77% (95% CI: 62
      89%) with 16% of the patients achieving complete response. The most frequent
      grade 3 or grade 4 hematological toxicities were neutropenia (64%),
      thrombocytopenia (36%), and febrile neutropenia (16%). The most common grade 3 or
      grade 4 nonhematological toxicities were gastrointestinal (30%) and electrolyte
      changes (23%). CONCLUSIONS: The addition of exisulind to a standard regimen of
      carboplatin and etoposide did not improve outcomes compared with historic
      controls treated with chemotherapy alone. Further evaluation of this regimen in
      small cell lung cancer is not warranted.

PMID- 19179901
TI  - Defining genomic alteration boundaries for a combined small cell and non-small
      cell lung carcinoma.
AB  - In the rare case of a male patient presenting with a combined small cell lung
      carcinoma (SCLC), large cell neuroendocrine carcinoma and adenocarcinoma, we used
      whole genome analysis by tiling-path array comparative genomic hybridization to
      evaluate the clonal relationship between nodules. In two areas of SCLC
      distinguishable by divergent neuroendocrine marker expression (CD56 and
      chromogranin-A), the presence of identical genomic breakpoints and rearrangements
      indicated a common origin, with the presence of additional distinct genomic
      alterations in these two components indicating diverging clonal evolution. The
      absence of shared genome alteration features for the adenocarcinoma and large
      cell neuroendocrine carcinoma components suggested that these tumors evolved
      independently from the SCLC. Taken together, the array comparative genomic
      hybridization data demonstrate the development and evolution of three independent
      primary lung cancers in close proximity to each other to form a combined
      carcinoma. Application of whole genome analysis shows the potential utility of
      high resolution molecular tools in resolving the origin and delineating the
      clonal relationships of a tumor that contains heterogeneous histologic components
      leading to an ambiguous histogenesis.

PMID- 19179903
TI  - A vanishing cardiac mass.

PMID- 19179902
TI  - A two-faced young woman.

PMID- 19179904
TI  - Treatment paradigms for advanced stage non-small cell lung cancer in the era of
      multiple lines of therapy.
AB  - The duration of first-line and the timing of second-line therapy for advanced non
      small cell lung cancer has been an area of recent investigation. Five trials have
      been performed that have investigated shorter (3-4 cycles) versus longer duration
      of platinum-based therapy; four trials revealed an equivalent overall survival
      with the shorter duration of therapy, and one trial revealed superior survival
      with the longer duration of therapy. The toxicity and quality of life data has
      either been equivalent or favored the shorter duration of therapy. Two trials
      have investigated the timing of a second-line therapy after completion of four
      cycles of platinum-based therapy versus the standard treatment paradigm of
      initiating second-line therapy upon disease progression. Both of these trials
      have revealed a statistically significant improvement in the progression-free
      survival, and a trend towards improved survival for the earlier use of second
      line therapy. Only 50 to 60% of patients on the standard treatment arm initiated
      second-line therapy, and the promising results observed are most likely related
      to the fact that a higher percentage of patients received second-line therapy on
      the experimental arm. Several trials have investigated maintenance chemotherapy,
      and these trials have not revealed a survival benefit probably due to the fact
      that many patients experience disease progression or unacceptable toxicity during
      the initial or maintenance therapy. The addition of a targeted agent (bevacizumab
      or cetuximab) to the initial chemotherapy and the continuation of the targeted
      agent after completion of the chemotherapy have yielded superior overall survival
      in comparison to chemotherapy alone. The incremental benefit of the maintenance
      therapy with the targeted agent is unknown.

PMID- 19179905
TI  - Prevention and management of bone metastases in lung cancer: a review.
AB  - Approximately 30 to 40% of patients with advanced lung cancer will develop bone
      metastases in the course of their disease, resulting in a significant negative
      impact on both morbidity and survival. Skeletal complications of bone metastases
      include pain, pathologic fractures, spinal cord compression, and hypercalcemia.
      Total medical care costs are greater among patients with bone metastases who
      develop skeletal complications. A randomized phase III trial of the third
      generation bisphosphonate zoledronic acid has shown clinical benefit in the
      management of a subgroup of patients with bone metastases from lung cancer.
      Zoledronic acid treatment was associated with a reduction in both the risk of,
      and time to, a skeletal-related event. One of the markers of bone resorption, N
      telopeptide, is both prognositic for development of skeletal-related events and
      predictive for benefit from zoledronic acid. In preclinical models,
      bisphosphonates have also demonstrated antitumor activity and are therefore
      currently being evaluated in adjuvant trials. Inhibition of the receptor
      activator of nuclear factor kappa B ligand-RANK pathway can reduce osteoclast
      mediated bone resorption, and trials comparing receptor activator of nuclear
      factor kappa B ligand inhibitors with bisphosphonates are ongoing, including
      patients with lung cancer. In this article, we review the management of bone
      metastases and hypercalcemia as well as potential future directions for bone
      directed therapies in patients with lung cancer.

PMID- 19179906
TI  - Hypertrophic osteoarthropathy masquerading as lower extremity cellulitis and
      response to bisphosphonates.
AB  - Hypertrophic osteoarthropathy (HOA) is characterized by clubbing of digits and,
      in more advanced stages, by periosteal new bone formation and synovial effusions.
      Secondary HOA typically occurs in the setting of intrathoracic malignancy,
      infections or lung metastases. We report a case with an atypical presentation of
      HOA. The prominent systemic signs, presentation limited to lower extremities only
      and an excellent response to bisphosphonates make this case unusual.

PMID- 19179907
TI  - An aortoesophageal fistula in patient with lung cancer after chemo-irradiation
      and subsequent esophageal stent implantation.
AB  - An aortoesophageal fistula (AEF) is uncommon but is frequently fatal. Most cases
      are attributable to a thoracic aortic aneurysm. Other common causes include
      malignant intrathoracic neoplasm, foreign body ingestion, endovascular stent
      graft repair for thoracic aortic disease, and esophageal surgery. We report a
      case of an AEF that developed after chemo-irradiation and subsequent esophageal
      stent implantation in patient with non-small cell lung cancer. The patient
      underwent self expanding metallic esophageal stent implantation for an esophageal
      stricture after chemotherapy and radiotherapy. However, 1 month later, he
      presented with hematemesis. Chest computed tomography and aortography revealed a
      fistula from the descending thoracic aorta to the stented esophagus. The patient
      expired 36 hours after initial hematemesis. To our knowledge, this is the first
      confirmed report of an AEF in patient with a nonesophageal malignancy that had
      undergone chemo-irradiation and subsequent esophageal stent implantation. We
      recommend that special caution be exercised when performing esophageal stent
      implantation in patients who have received prior radiotherapy to the thorax
      including the esophagus.

PMID- 19179908
TI  - Prolonged remission of disseminated atypical adenomatous hyperplasia under
      gefitinib.
AB  - Atypical adenomatous hyperplasia (AAH) is a putative precursor of
      bronchioloalveolar carcinoma (BAC) and adenocarcinoma of the lung, developing
      from terminal respiratory unit cells. AAH and BAC lesions typically present as
      ground-glass opacities at spiral chest computed tomography. Epidermal growth
      factor receptor polysomy/mutations, conferring higher sensitivity to Gefitinib,
      are frequent in BAC but less common in AAH. We describe an interesting case of
      disseminated AAH showing a sustained remission under Gefitinib therapy.

PMID- 19179909
TI  - Rupture of a cerebral arteriovenous malformation in a patient treated with
      bevacizumab.

PMID- 19179910
TI  - Radiographic analysis of the cervical spine in patients with retro-odontoid
      pseudotumors.
AB  - STUDY DESIGN: A retrospective review of 10 consecutive patients with a
      noninflammatory retro-odontoid pseudotumor. OBJECTIVE: To examine the
      radiographic characteristics in patients with a retro-odontoid pseudotumor and to
      evaluate the efficacy of posterior fusion. SUMMARY OF BACKGROUND DATA: A retro
      odontoid pseudotumor, a reactive fibrocartilaginous mass, is known to develop
      after chronic atlantoaxial instability; however, one-third of the reported cases
      showed no overt atlantoaxial instability. The pathomechanism for such "atypical"
      cases remains unclear, although altered cervical motion secondary to ossification
      of the anterior longitudinal ligament (OALL) or severe spondylosis has been
      implicated. METHODS: We reviewed the charts and radiographs of 10 patients with a
      retro-odontoid pseudotumor who underwent surgery. Preoperative radiographs were
      evaluated for atlas-dens interval (ADI), presence of OALL, range of motion, and
      segmental motion adjacent to the atlantoaxial joint. Computed tomography was
      evaluated for degenerative changes of zygapophysial joints. RESULTS: There were 6
      men and 4 women. Atlantoaxial instability (ADI >4 mm) was observed in 2 patients.
      ADI was less than 3 mm in 5 patients. Frequent association of OALL (6 patients)
      and marked decrease in C2 to C7 range of motion (mean, 17.6 degrees ; range, 3
      degrees-36 degrees ) were noted. Ankylosis of O-C1 was observed in 4 patients and
      C2 to C3 in 6. Severe degenerative change of C2 to C3 zygapophysial joint was
      observed in 4 patients. The patients underwent occipito-cervical fusion (9
      patients) or direct removal of the pseudotumor (1 patient). Postoperative
      magnetic resonance imaging invariably demonstrated the mass regression.
      CONCLUSION: Retro-odontoid pseudotumors were not always associated with
      radiographic atlantoaxial instability. Our data indicate that extensive OALL and
      ankylosis of the adjacent segments are risk factors for the formation of the
      pseudotumor. Retro-odontoid pseudotumors may develop as an "adjacent segment
      disease" after altered biomechanics of the cervical spine, especially those in
      the adjacent segments. Posterior fusion was effective even in cases without
      radiographic atlantoaxial instability.

PMID- 19179911
TI  - Effect of osteoporosis on morphology and mobility of the lumbar spine.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: The purpose of this study was to
      examine disc morphology and spinal mobility in subjects with varying degrees of
      osteoporosis. SUMMARY OF BACKGROUND DATA: There was limited information on the
      effect of osteoporosis on lumbar morphology and spinal mobility. It was also
      unclear how osteoporosis affects the nonosseous tissues such as the
      intervertebral disc. METHODS: Ninety elderly subjects with varying bone mineral
      densities (22 normal, 28 osteopenia, 40 osteoporosis) were recruited from an
      osteoporosis clinic. Lateral radiographs and magnetic resonance images of their
      lumbar spines were obtained. An electromagnetic tracking device was employed to
      measure the ranges of motion of the whole lumbar spine. RESULTS: Although the
      thoracic spine had been shown to have decreased anterior vertebral body height in
      subjects with osteoporosis, this study revealed that the anterior height was
      increased in the lumbar region. Osteoporosis was associated with expansion of the
      middle of the disc with corresponding collapse of vertebral bodies, but
      osteoporosis was found not to be related to either disc preservation or
      degeneration. No significant change in spinal mobility was observed in patients
      with osteoporosis. CONCLUSION: Osteoporosis does not only affect the bone but
      also the nonosseous tissues. It was found to be associated with expansion of the
      intervertebral disc, which was likely to be secondary to changes in the vertebral
      endplate.

PMID- 19179912
TI  - Cervical segmental motion induced by shoulder abduction assessed by magnetic
      resonance imaging.
AB  - STUDY DESIGN: A comparative measurement study of in vivo cervical rotation,
      induced by shoulder abduction, measured using magnetic resonance imaging.
      OBJECTIVE: The purpose of this study was to clarify the kinematics between
      cervical rotation and shoulder abduction. SUMMARY OF BACKGROUND DATA: Although it
      is believed that abduction of the shoulder induces rotational movement of the
      cervical spine, there have been no in vivo studies to measure the influence of
      shoulder movement on the cervical spine at a segmental level. METHODS: Twenty-two
      participants [12 men, age 24.2 years (range, 20-32 years)] without history of
      significant cervical spine disorders were studied. Kinematic magnetic resonance
      imaging of the cervical spine was performed with a 0.2-T horizontally open unit.
      Cervical rotation was assessed with the shoulder in 0, 30, 60, 90, and 120
      degrees abduction. In each position, 2 conditions were applied. Firstly no muscle
      contraction with the arm relaxed and supported and secondly isometric contraction
      of the shoulder abductors. Isometric contraction was standardized by a 2-kg
      adduction force applied at the wrist, perpendicular to the arm. RESULTS: No
      statistically significant differences were found in cervical segmental rotation
      between each shoulder position under passive conditions (P > 0.05). When the
      right shoulder was abducted, with isometric contraction, at each shoulder
      position up to 90 degrees abduction, each cervical vertebra tended to rotate to
      the left and the largest vertebral movement was seen at C6, being 5.20 degrees
      (SD = 3.66) at 0 degrees abduction. The pattern of movement changed at 120
      degrees abduction, with C1 and C2 rotating to the right. CONCLUSION: Shoulder
      abduction up to 90 degrees induced left rotation throughout the cervical spine
      only in the presence of muscle contraction, with the largest movement occurring
      at C6. A contrasting pattern of upper and lower cervical rotation occurred when
      the arm was positioned in 120 degrees abduction.

PMID- 19179913
TI  - Favorable response to intrathecal, but not oral, baclofen of priapism in a
      patient with spinal cord injury.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To retrieve data about the utility of
      intrathecal baclofen for the treatment of otherwise refractory priapism that may
      occur in patients with spinal spasticity. SUMMARY OF BACKGROUND: Baclofen exerts
      well-known inhibitory effects on sexual function both in animals and humans. This
      observation led to the introduction of oral baclofen in the treatment of
      refractory and recurrent idiopathic priapism. METHODS: We report a 41-year-old
      male patient who sustained a severe traumatic spinal cord injury in a motor
      vehicle accident. On clinical examination he presented with tetraplegia (motor
      level C3). Initial cervical magnetic resonance imaging showed a C3 to C4 lesion
      with a herniated disc and compression of the dural sac. One month later the
      patient developed priapism episodes. RESULTS: He received oral baclofen with only
      minimal beneficial effect on priapism. Eight months postinjury the patient
      underwent a test-trial with intrathecal baclofen bolus, which caused absence of
      priapism for 10 hours. One month later, an intrathecal pump system was implanted,
      leading to absence of priapism episodes. CONCLUSION: In the present case report,
      reduction of supraspinal control on the spinal cord may have induced an up
      regulation of GABAB receptors, which are involved in penile tumescence. The
      trauma induced also liberation of penile reflexes with episodes of priapism.
      Normal full blood count and color duplex ultrasonography of the penis excluded a
      vascular genesis of priapism. This is the first report about the utility of
      intrathecal baclofen for the successful control of otherwise untreatable priapism
      in a patient with severe spinal spasticity. Hence, evaluation of intrathecal
      baclofen should be considered in patients suffering from severe and/or frequent
      priapism when oral baclofen and/or hormonal therapy are ineffective. The
      beneficial effect of intrathecal, but not oral baclofen, in our patient suggests
      a dose-dependent effect.

PMID- 19179915
TI  - Effectiveness of a lumbar belt in subacute low back pain: an open, multicentric,
      and randomized clinical study.
AB  - STUDY DESIGN: Multicentric, randomized, and controlled study of clinical
      evaluation of medical device in subacute low back pain. OBJECTIVE: To evaluate
      the effects of an elastic lumbar belt on functional capacity, pain intensity in
      low back pain treatment, and the benefice on medical cost. SUMMARY OF BACKGROUND
      DATA: There is limited evidence of efficiency of lumbar supports for treatment of
      low back pain. There is also a lack of the methodology in the studies reported on
      the efficiency of this device. METHODS: This study is randomized, multicentric,
      and controlled with 2 groups: a patient group treated with a lumbar belt (BWG)
      and a control group (CG). The main criteria of clinical evaluation were the
      physical restoration assessed with the EIFEL scale, the pain assessed by a visual
      analogic scale, the main economical criteria was the overall cost of associated
      medical treatments. RESULTS: One hundred ninety-seven patients have participated.
      The results show a higher decrease in EIFEL score in BWG than CG between days 0
      and 90 (7.6 +/- 4.4 vs. de 6.1 +/- 4.7;P = 0.023). Respectively significant
      reduction in visual analogic scale was also noticed (41.5 +/- 21.4 vs. 32.0 +/-
      20; P = 0.002). Pharmacologic consumption decreased at D90 (the proportion of
      patients who did not take any medication in BWG is 60.8% vs. 40% in CG;P =
      0.029). CONCLUSION: Lumbar belt wearing is consequent in subacute low back pain
      to improve significantly the functional status, the pain level, and the
      pharmacologic consumption. This study may be useful to underline the interest of
      lumbar support as a complementary and nonpharmacologic treatment beside the
      classic medication use in low back pain treatment.

PMID- 19179916
TI  - Graded exercise for recurrent low-back pain: a randomized, controlled trial with
      6-, 12-, and 36-month follow-ups.
AB  - STUDY DESIGN: The study was a randomized controlled trial. Treatment was for 8
      weeks, with follow-up posttreatment and at 6-, 12-, and 36- months. OBJECTIVE:
      The purpose was to evaluate the effect of a graded exercise intervention
      emphasizing stabilizing exercises in patients with nonspecific, recurrent low
      back pain (LBP). SUMMARY OF BACKGROUND DATA: Exercise therapy is recommended and
      widely used as treatment for LBP. Although stabilizing exercises are reportedly
      effective in the management of certain subgroups of LBP, such intervention
      protocols have not yet been evaluated in relation to a more general exercise
      regimen in patients with recurrent LBP, all at work. METHODS: Seventy-one
      patients recruited consecutively (36 men, 35 women) with recurrent nonspecific
      LBP seeking care at an outpatient physiotherapy clinic were randomized into 2
      treatment groups; graded exercise intervention or daily walks. The primary
      outcome was perceived disability and pain at 12-month follow-up. Secondary
      outcomes included physical health, fear-avoidance, and self-efficacy beliefs.
      RESULTS: Of the participants, 83% provided data at the 12-month follow-up and 79%
      at 36 months. At 12 months, between-group comparison showed a reduction in
      perceived disability in favor of the exercise group, whereas such an effect for
      pain emerged only immediately postintervention. Ratings of physical health and
      self-efficacy beliefs also improved in the exercise group over the long term,
      though no changes were observed for fear-avoidance beliefs. CONCLUSION: A graded
      exercise intervention, emphasizing stabilizing exercises, for patients with
      recurrent LBP still at work seems more effective in improving disability and
      health parameters than daily walks do. However, no such positive results emerged
      for improvement regarding pain over a longer term, or for fear-avoidance beliefs.

PMID- 19179917
TI  - Posterior lumbar interbody fusion using nonresorbable poly-ether-ether-ketone
      versus resorbable poly-L-lactide-co-D,L-lactide fusion devices: a prospective,
      randomized study to assess fusion and clinical outcome.
AB  - STUDY DESIGN: A prospective randomized clinical study. OBJECTIVE.: To assess
      fusion, clinical outcome, and complications. SUMMARY OF BACKGROUND DATA:
      Resorbable poly-L- lactide-co-D,L-lactide (PLDLLA) cages intended to aid spinal
      interbody fusion have been introduced into clinical practice within the last
      decade. Although early case series show promising results with respect to fusion
      rate, worries persist with regards to efficacy and potential risks of early
      failure of these implants. Despite widespread clinical application this is the
      first randomized prospective study to assess clinical and radiologic outcomes of
      PLDLLA cage compared with a traditionally applicable counterpart. METHODS: Twenty
      six patients were randomly assigned to undergo instrumented posterior lumbar
      interbody fusion whereby either a nonresorbable poly-ether-ether-ketone (PEEK)
      cage or a resorbable PLDLLA cage was implanted to aid fusion. Fusion rate,
      subsidence, and clinical outcome based on visual analog scale scores for leg pain
      and back pain, as well as Oswestry Disability Index and SF-36 questionnaires were
      documented and analyzed. Complications and adverse events were recorded. RESULTS:
      Fusion rate was significantly higher with the PEEK cage compared with PLDLLA cage
      (Fisher exact test, P = 0.0302). Rate of subsidence was significantly higher with
      the PLDLLA cage compared to PEEK cage (Fisher exact test, P = 0.0414). The PEEK
      group demonstrated greater improvement in the Oswestry Disability Index compared
      with the PLDLLA group (Fisher exact test, P = 0.1414). Two cases of mild to
      moderate osteolysis were seen in the PLDLLA group. CONCLUSION: Our results
      strongly suggest that PLDLLA cage proffers a lower rate of fusion compared with
      PEEK cage, and also confirms that the efficacy of PLDLLA cage in enhancing
      interbody spinal fusion is yet to be established. The higher rate of subsidence
      and occurrence of osteolysis seen in association with PLDLLA cages in this study
      remain worrisome.

PMID- 19179918
TI  - RhBMP-2 versus iliac crest bone graft for lumbar spine fusion in patients over 60
      years of age: a cost-utility study.
AB  - STUDY DESIGN: Randomized clinical trial. OBJECTIVE: To perform a cost-utility
      analysis using actual cost data from a randomized clinical trial of patients over
      60 years old who underwent posterolateral fusion using either rhBMP-2/ACS or
      iliac crest bone graft (ICBG). SUMMARY BACKGROUND DATA: Bone morphogenetic
      protein has been shown to be an effective bone graft substitute for spine fusion.
      However, a clinical trial-based economic analysis of rhBMP-2/ACS compared with
      iliac crest bone graft has not been done. METHODS: Patients over 60 years old
      requiring decompression and posterolateral fusion were randomized to rhBMP-2/ACS
      (n = 50) or ICBG (n = 52). A dedicated hospital coder and research nurse tracked
      each patient to determine direct costs of inpatient care and all postoperative
      healthcare encounters up to 2 years after surgery. Preoperative and 2-year
      postoperative SF-6D utility scores for each patient were determined. A decision
      tree was created, which included the probability of complications, need for
      additional treatments and revision surgery; and the costs associated with initial
      surgery and treatment for complications and additional treatment for continued
      spine symptoms; and utility scores. RESULTS: The mean total 2-year cost for care
      (excluding complication and additional spine treatment costs) was $34,235 in the
      ICBG group and $36,530 in the rhBMP-2/ACS group. For the entire group, the mean
      cost to treat a major complication was $10,888, the cost of revision surgery for
      nonunion was $46,852, and additional treatment for spine-related events was
      $5892. In the ICBG group, 8 patients had complications; 20 had additional
      interventions, 5 of whom required revision for nonunion. In the rhBMP-2/ACS
      group, 6 patients had complications, 10 had additional interventions, and 1
      required revision for nonunion. The cost of using rhBMP-2/ACS was $39,967 with a
      0.11 mean improvement in SF-6D; and for ICBG the cost was $42,286 with a mean
      improvement of 0.10 in SF-6D. CONCLUSION: There are more complications, increased
      need for additional treatment and revision surgery in patients over 60 years old
      receiving ICBG compared with rhBMP-2/ACS. This may account for higher costs and
      lower improvements in utility seen in patients receiving ICBG compared with rhBMP
      2/ACS in this study population.

PMID- 19179919
TI  - Secular trend in the opening of the sacral canal: an Australian study.
AB  - STUDY DESIGN: Computer tomography scans were used to asses the opening of the
      sacral canal. OBJECTIVE: We investigated the prevalence of sacral spina bifida
      occulta in 2 population groups: born 1940 to 1950 and 1980 to 1990. SUMMARY OF
      BACKGROUND DATA: Comparison of the prevalence of spina bifida occulta in the
      first-century Pompeii with that in 20th century European and Mediterranean
      populations indicates that the degree of the closure of vertebral arches in the
      sacrum has undergone changes and the prevalence of spina bifida occulta is
      increasing. METHODS: Transverse computer tomograph scans and multiplanar
      reconstruction images of sacra of 100 males and 100 females born 1940 to 1950 and
      100 males and 100 females born 1980 to 1990 were used after ethics committee
      approval. RESULTS: The individuals born later have significantly more open sacral
      arches when compared with those born 40 years earlier, especially in the
      midsacral region. Also, males have open sacral arches in the rostral segments of
      the sacrum more than females. CONCLUSION: This study demonstrates a secular trend
      in the opening of the sacral canal in both sexes that occurred within 2
      generations. Also, the increased prevalence of open sacral canal in males
      suggests a different response between sexes to the forces of evolution.

PMID- 19179920
TI  - Prospective design delineation and subsequent in vitro evaluation of a new
      posterior dynamic stabilization system.
AB  - STUDY DESIGN: Finite element and in vitro study. OBJECTIVE: Finite element
      calculations to delineate a dynamic fixator and confirmation with an in vitro
      experiment. SUMMARY AND BACKGROUND DATA: In the last few years, there was a
      paradigm shift from rigid to dynamic fixation of spinal segments. However, some
      so-called dynamic implants like the Dynesys performed still stiffer than
      anticipated. The aim of this study was to optimize a dynamic stabilization
      system. METHODS: The development steps of this implant design can be summarized
      in a development loop. First, a finite element model of an intact human L4-L5
      segment was used to delineate implant stiffness parameters for the implant, in
      consideration of clinical concerns and safety aspects. These data were used in a
      second step, leading to the final implant design. This development process was
      completed with an appropriate in vitro experiment. The optimal axial and bending
      stiffness were computed to reduce the spinal motion by 30%. For the validation
      process, in vitro tests were performed on 6 human lumbar spinal segments L2-L3
      with a median age of 52. The model and the specimens were loaded with pure
      unconstrained moments of 7.5 Nm in flexion, extension, lateral bending, and axial
      rotation. RESULTS: This study demonstrated the advantages of employing a finite
      element model for the implant parameter delineation. It was possible to
      prospectively outline the needed stiffness parameters for a desired spinal range
      of motion achievement. CONCLUSION: In summary, FEM may accelerate the development
      and the realization of a new implant design.

PMID- 19179921
TI  - A segmental partial laminectomy for cervical spondylotic myelopathy: anatomical
      basis and clinical outcome in comparison with expansive open-door laminoplasty.
AB  - STUDY DESIGN: A comparative study regarding the clinical outcome of the 2
      different surgical procedures for patients with cervical spondylotic myelopathy
      (CSM). OBJECTIVES: To describe the anatomic basis of a segmental partial
      laminectomy (SPL) for the treatment of cervical spondylotic myelopathy and to
      compare the clinical outcome with traditional C3 to C7 expansive open-door
      laminoplasty (ELAP). SUMMARY OF BACKGROUND DATA: Laminoplasty has been widely
      accepted for the treatment of CSM. However, some disadvantages have also been
      recognized. To resolve these problems, a SPL was performed. No previous studies
      have been reported regarding this surgical procedure. METHODS: A total of 13
      human cadavers were studied to analyze the spinal cord compression of cervical
      spondylosis. Twenty-six patients who underwent a SPL and 13 age- and gender
      matched patients who underwent traditional C3-C7 ELAP were analyzed for their
      Japanese Orthopedic Association score, axial neck pain, and radiographic
      parameters (lordotic angle and ROM of cervical spine). RESULTS: Based on cadaver
      studies, compression of the spinal cord was present in the articular segment, but
      not in the intraosseous segment. The removal of the ligamentum flavum and the
      superior edge of the lower lamina was sufficient for minimum posterior
      decompression of the cervical spinal cord.In comparison with the ELAP, the
      patients who underwent an SPL showed a similar recovery of the Japanese
      Orthopedic Association score, but the maintenance of the sagittal alignment and
      the range of motion were better after the SPL and postoperative neck and/or
      shoulder complaints also seemed to be reduced. CONCLUSION: A SPL, may therefore,
      be a useful and effective surgical procedure for cervical spondylotic myelopathy.

PMID- 19179922
TI  - Spinal cord shift on magnetic resonance imaging at 24 hours after cervical
      laminoplasty.
AB  - STUDY DESIGN: A prospective study in 19 patients after cervical laminoplasty,
      using magnetic resonance imaging. OBJECTIVE: To evaluate the value of spinal cord
      shift at 24 hours after cervical laminoplasty. SUMMARY OF BACKGROUND DATA:
      Postoperative C5 palsy is a noticeable complication within 1 week after cervical
      laminoplasty. The root tethering due to the posterior shift of the spinal cord
      after laminoplasty was reported as one of the causes of C5 palsy. However, the
      spinal cord shift after surgery within 1 week is unknown. METHODS: The posterior
      shift of the spinal cord was measured in 19 consecutive patients on magnetic
      resonance images at 24 hours and 2 weeks after cervical laminoplasty. RESULTS:
      The mean posterior shift of the spinal cord at 24 hours was 2.8 mm, with the
      maximum at the C5 level, decreasing to 1.9 mm at 2 weeks. The posterior shift of
      the spinal cord at C5 was correlated with the amount of the dura mater at C4, C5,
      and C6 levels. In a patient with right C5 palsy, posterior shift at C5 level was
      5.5 mm, decreasing to 3.0 mm at 2 weeks after surgery. The posterior shift of the
      spinal cord was not correlated with the sagittal alignment. CONCLUSION: The
      posterior shift of the spinal cord at 24 hours had a tendency to shift more
      posteriorly than that observed at 2 weeks after cervical laminoplasty. C5 palsy
      may be prevented if the expansion of dura mater, which is strongly correlated
      with the posterior shift, can be controlled.

PMID- 19179923
TI  - Influence of lumbar lordosis restoration on thoracic curve and sagittal position
      in lumbar degenerative kyphosis patients.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVES: To determine postsurgical
      correlations between thoracic and lumbar sagittal curves in lumbar degenerative
      kyphosis (LDK) and to determine predictability of spontaneous correction of
      thoracic curve and sacral angle after surgical restoration of lumbar lordosis and
      fusion. SUMMARY OF BACKGROUND DATA: To our knowledge, there are only a limited
      number of articles about the relationship between thoracic and lumbar curve in
      sagittal thoracic compensated LDK. METHODS: Retrospective review of 53
      consecutive patients treated with combined anterior and posterior spinal
      arthrodesis. We included patients with sagittal thoracic compensated LDK caused
      by sagittal imbalance in this study. Total lumbar lordosis, thoracic kyphosis,
      sacral slope, and C7 plumb line were measured on the pre- and postoperative whole
      spine lateral views. Postoperative changes in thoracic kyphosis, sacral slope,
      and C7 plumb line according to the surgical lumbar lordosis restoration were
      measured and evaluated. RESULTS: The mean preoperative sagittal imbalance by
      plumb line was 78.3 mm (+/-76.5); this improved to 13.6 mm (+/-25) after surgery
      (P < 0.0001). Mean lumbar lordosis was 9.4 degrees (+/-19.2) before surgery and
      increased to 38.4 degrees (+/-13.1) at follow-up (P < 0.0001). Mean thoracic
      kyphosis was 1.1 degrees (+/-12.7) before surgery and increased to 17.6 degrees
      (+/-12.2) at follow-up (P < 0.0001). Significant preoperative correlations
      existed between kyphosis and lordosis (r = 0.772, P < 0.0001) and between
      lordosis and sacral slope (r = 0.785, P < 0.0001). Postoperative lumbar lordosis
      is correlated to thoracic kyphosis increase (r = 0.620, P < 0.0001).
      Postoperative lumbar lordosis is correlated to sacral slope increase (r = 0.722,
      P < 0.0001). CONCLUSION: Reciprocal relationship exists between lumbar lordosis
      and thoracic kyphosis in sagittal thoracic compensated LDK. Surgical restoration
      of lumbar lordosis for LDK brings about high level of statistical correlation to
      thoracic kyphosis improvement. At the same time, the reciprocal relationship is
      maintained.

PMID- 19179924
TI  - Radiographic assessment of lumbar facet distance spacing and pediatric
      spondylolysis.
AB  - STUDY DESIGN: Retrospective radiographic review. OBJECTIVE: The purpose of this
      article was to explore the relationship between interfacet spacing and pediatric
      spondylolysis. SUMMARY OF BACKGROUND DATA: Recent literature suggests that a
      potential cause of spondylolytic defects in adults is a narrowed interfacet
      spacing in the lower lumbar spine. This lack of space places them at increased
      risk for pars fractures with repetitive lumbar hyperextension. This relationship
      has not been explored in a pediatric population. METHODS: The anteroposterior
      lumbar spine radiographs of 41 pediatric patients with spondylolytic defects were
      compared with 41 unaffected controls. A standard digital caliper was used to
      measure interfacet distance. Vertebral body width and interpedicular distance
      were recorded as internal standards to control for varying vertebral size.
      Statistical analysis exploring the relationships of interfacet distances between
      the affected and unaffected groups was performed using a Mann-Whitney U test.
      RESULTS: The absolute increase in interfacet distance between adjacent levels was
      significantly smaller at the L4/L5 level in spondylolytic individuals (P =
      0.023). When interpedicular distance was used to standardize for vertebral body
      size, a significantly smaller increase in the interpedicular distance was noted
      at the L4/5 level in spondylolytic individuals (P = 0.026). Similar results were
      obtained when body width was used to standardize for vertebral body size (P <
      0.001). A similar trend was noticed at the L3/4 level when standardizing with
      interpedicular distance although these results were not significant (P = 0.098).
      CONCLUSION: A likely explanation for the etiology of lumbar pars defects is
      insufficient caudal increase in lumbar interfacet spacing. Further prospective
      studies are necessary to determine if unaffected individuals with a narrowed
      interfacet spacing are at increased risk of developing spondylolytic defects
      later in life.

PMID- 19179925
TI  - Thromboembolic disease in spinal surgery: a systematic review.
AB  - STUDY DESIGN: Systematic review of the literature and analysis of pooled data.
      OBJECTIVES: To better understand the incidence of thromboembolic disease in
      postoperative spinal patients, and to establish a starting point for defining
      appropriate postoperative prophylaxis protocols. SUMMARY OF BACKGROUND DATA: The
      risk of thromboembolic disease is well studied for some orthopedic procedures.
      However, the incidence of postoperative thromboembolic disease is less well
      defined in patients who have had spinal surgery. METHODS: The MEDLINE database
      was queried using the search terms deep venous thrombosis or DVT, pulmonary
      embolus, thromboembolic disease, and spinal or spine surgery. Abstracts of all
      identified articles were reviewed. Detailed information from eligible articles
      was extracted. Data were compiled and analyzed by simple summation methods when
      possible to stratify rates of DVT and/or pulmonary embolus for a given
      prophylaxis protocol, screening method, and type of spinal surgery. RESULTS:
      Twenty-five articles were eligible for full review. DVT risk ranged from 0.3% to
      31%, varying between patient populations and methods of surveillance. Pooling
      data from the 25 studies, the overall rate of DVT was 2.1%. DVT rate was
      influenced by prophylaxis method: no prophylaxis, 2.7%; compression stockings
      (CS), 2.7%; pneumatic sequential compression device (PSCD), 4.6%; PSCD and CS,
      1.3%; chemical anticoagulants, 0.6%; and inferior vena cava filters with/without
      another method of prophylaxis, 22%. DVT rate was also influenced by the method of
      diagnosis, ranging from 1% to 12.3%. CONCLUSION: As risk of DVT after routine
      elective spinal surgery is fairly low, it seems reasonable to use CS with PSCD as
      a primary method of prophylaxis. There is insufficient evidence to support or
      refute the use of chemical anticoagulants in routine elective spinal surgery. In
      addition, there is insufficient evidence to suggest that screening patients
      undergoing elective spinal surgery with ultrasound or venogram is routinely
      warranted.

PMID- 19179927
TI  - Androgens, estrogens, and metabolic syndrome at midlife.

PMID- 19179926
TI  - Cervical polyps in postmenopausal women: is there a difference in risk?
AB  - OBJECTIVE: The aim of this study was to evaluate cervical polyps and assess
      whether postmenopausal women are at higher risk for abnormalities than their
      premenopausal counterparts. METHODS: After institutional review board approval,
      the Hartford Hospital pathology database was retrospectively searched for cases
      of endocervical polyps removed from September 1999 through January 2008,
      inclusive. The presence of malignancy, dysplasia, and atypia was recorded, along
      with demographic information. RESULTS: A total of 2,458 polyps were analyzed. The
      mean +/- SD age was 48.6 +/- 10.7 years, with a range from 16 to 95 years. Most
      specimens were from private offices (95%) and obstetrics and gynecology practices
      (98.5%). The population was 82.5% white, 3.5% African-American, 5.2% Hispanic,
      0.4% Asian, and 8.3% "other." For the women younger than 50 years, the prevalence
      of malignancy, dysplasia, and atypia within a cervical polyp was 0.1%, 0.7%, and
      1.9%, respectively, compared with 0.1%, 0.2%, and 1.1% for the women 50 years or
      older (P = 0.846, 0.063, and 0.144, respectively). The prevalence of "any
      abnormality" (malignancy, dysplasia, or atypia) within the polyp among women
      younger than 50 years was 2.7% compared with 1.4% in women 50 years or older (P =
      0.034). Most atypia was found in the teens and 20s; most dysplasia in the 30s to
      50s; and most cancers in perimenopause to postmenopause (>or=48 y). CONCLUSIONS:
      The prevalence of any abnormality within a cervical polyp is significantly lower
      in postmenopausal, compared with premenopausal, women. Younger women (teenagers
      to 20s) have little risk associated with cervical polyps. Middle-aged women (30s
      50s) have a higher risk of dysplasia. Women in the perimenopausal to
      postmenopausal years have a slightly higher likelihood of a malignancy associated
      with cervical polyps.

PMID- 19179929
TI  - Macular degeneration. An age-related cause of vision loss.

PMID- 19179930
TI  - Hot flashes could be sign of underlying vascular problems.

PMID- 19179931
TI  - Government issues new physical activity guidelines for Americans.

PMID- 19179932
TI  - Gait aids. These tools are made for walking.

PMID- 19179933
TI  - Mayo Clinic office visit. Molecular breast imaging. An interview with Deborah
      Rhodes, M.D.

PMID- 19179934
TI  - Training for an event. A carrot to keep you exercising.

PMID- 19179935
TI  - I had my pneumococcal shot at age 65. Do I need to be revaccinated?

PMID- 19179936
TI  - Is it ok to throw old or unused medicines in the trash?

PMID- 19179937
TI  - Treatment response and redefining diagnostic boundaries.

PMID- 19179938
TI  - Diagnostic dilemmas associated with bipolar disorder after traumatic brain
      injury.

PMID- 19179939
TI  - Anxiety disorders and rheumatic Fever: is there an association?
AB  - INTRODUCTION: Findings suggest that obsessive-compulsive disorder (OCD) and
      related disorders, referred to as obsessive-compulsive spectrum disorders
      (OCSDs), are more common in patients with rheumatic fever (RF). OBJECTIVES: To
      determine whether RF or Sydenham's chorea increases the probability of anxiety
      disorders in the relatives of individuals with RF with and without SC. METHODS:
      This was a case-control family study in which 98 probands and 389 first-degree
      relatives (FDRs) were assessed using structured psychiatric interviews. A Poisson
      regression model was used to determine whether the presence of any disorder in
      one family member influences the rate of disorders in the remaining family
      members. RESULTS: Generalized anxiety disorder (GAD) occurred more frequently in
      the FDRs of RF probands than in those of control probands (P=.018). The presence
      of RF, GAD, or separation anxiety disorder in one family member significantly
      increased the chance of OCSDs in another member of the family. CONCLUSION: We
      found familial aggregation among RF, GAD, and OCSDs. Clinicians should be aware
      of the possible familial relationship between GAD and OCSDs in their RF patients
      and their family members, which may suggest a genetic component between them.
      Further studies on OCD should include anxiety disorders to better define OCD
      spectrum.

PMID- 19179940
TI  - Long-term, open-label extension study of guanfacine extended release in children
      and adolescents with ADHD.
AB  - INTRODUCTION: Guanfacine is a noradrenergic agonist that is believed to improve
      symptoms of attention-deficit/hyperactivity disorder (ADHD) through selective
      actions at alpha2A-adrenoceptors in the prefrontal cortex. A recent double-blind,
      multicenter trial supports the efficacy and safety of guanfacine extended release
      (GXR) for pediatric ADHD. This long-term, open-label extension was conducted to
      study the safety profile and effectiveness of GXR for up to 2 years. METHODS:
      Subjects were 240 children 6-17 years of age with a diagnosis of ADHD who
      participated in the preceding randomized trial. GXR was initiated at 2 mg/day and
      titrated as needed in 1-mg increments to a maximum of 4 mg/day to achieve optimal
      clinical response. RESULTS: The most common adverse events were somnolence
      (30.4%), headache (26.3%), fatigue (14.2%), and sedation (13.3%). Somnolence,
      sedation, and fatigue were usually transient. Cardiovascular-related adverse
      events were uncommon, although small reductions in mean blood pressure and pulse
      rate were evident at monthly visits. ADHD Rating Scale, Version IV, total and
      subscale scores improved significantly from baseline to endpoint for all dose
      groups (P<.001 for all comparisons, intent-to-treat population). CONCLUSION: Long
      term treatment with GXR was generally safe for up to 24 months of treatment, and
      effectiveness was maintained over this treatment period.

PMID- 19179941
TI  - Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions
      challenge classical notions of antihistamines.
AB  - Numerous "antihistamines" as well as various psychotropic medications with
      antihistamine properties are widely utilized to treat insomnia. Over-the-counter
      sleep aids usually contain an antihistamine and various antidepressants and
      antipsychotics with antihistamine properties have sedative-hypnotic actions.
      Although widely used for the treatment of insomnia, many agents that block the
      histamine H1 receptor are also widely considered to have therapeutic limitations,
      including the development of next-day carryover sedation, as well as problems
      with chronic use, such as the development of tolerance to sedative-hypnotic
      actions and weight gain. Although these clinical actions are classically
      attributed to blockade of the H1 receptor, recent findings with H1 selective
      agents and H1 selective dosing of older agents are challenging these notions and
      suggest that some of the clinical limitations of current H1-blocking agents at
      their currently utilized doses could be attributable to other properties of these
      drugs, especially to their simultaneous actions on muscarinic, cholinergic, and
      adrenergic receptors. Selective H1 antagonism is emerging as a novel approach to
      the treatment of insomnia, without tolerance, weight gain, or the need for the
      restrictive prescription scheduling required of other hypnotics.

PMID- 19179942
TI  - Treatment of severe, treatment-refractory obsessive-compulsive disorder: a study
      of inpatient and community treatment.
AB  - INTRODUCTION: This research reports on a prospective outcome study of two cohorts
      of patients with severe, chronic, resistant obsessive-compulsive disorder (OCD).
      METHODS: One cohort consisted of a total of 52 patients treated in an inpatient
      setting, while the second group comprised 65 patients treated in a community
      outpatient setting. Treatment consistent primarily of intensive graded exposure
      and self-imposed response prevention augmented with cognitive restructuring.
      RESULTS: The groups demonstrated significant improvement over the course of
      treatment. In the inpatient and community groups, there was significant
      improvement over the first 12 weeks of treatment, and further improvement between
      12 and 24 weeks. CONCLUSION: These results suggest that even for patients who
      have demonstrated treatment-resistance, there may be benefit in intensive
      behavioral treatment of OCD. In addition it was found that even for those
      patients with the most profound refractory OCD and complicating factors inpatient
      stays of up to 24 weeks were effective in reducing symptoms.

PMID- 19179943
TI  - Improving the prediction of treatment response in depression: integration of
      clinical, cognitive, psychophysiological, neuroimaging, and genetic measures.
AB  - Antidepressants are important in the treatment of depression, and selective
      serotonin reuptake inhibitors are first-line pharmacologic options. However, only
      50% to 70% of patients respond to first treatment and <40% remit. Since
      depression is associated with substantial morbidity, mortality, and family
      burden, it is unfortunate and demanding on health resources that patients must
      remain on their prescribed medications for at least 4 weeks without knowing
      whether the particular antidepressant will be effective. Studies have suggested a
      number of predictors of treatment response, including clinical,
      psychophysiological, neuroimaging, and genetics, each with varying degrees of
      success and nearly all with poor prognostic sensitivity and specificity. Studies
      are yet to be conducted that use multiple measures from these different domains
      to determine whether sensitivity and specificity can be improved to predict
      individual treatment response. It is proposed that a focus on standardized
      testing methodologies across multiple testing modalities and their integration
      will be crucial for translation of research findings into clinical practice.

PMID- 19179944
TI  - New perspectives in the diagnosis and management of insomnia. Introduction.

PMID- 19179945
TI  - Insomnia etiology and comorbidity.

PMID- 19179946
TI  - Gender, age, and the risk of insomnia.

PMID- 19179947
TI  - New directions in the pharmacologic treatment of insomnia.

PMID- 19179948
TI  - Case studies in the advancement of Parkinson's disease.
AB  - Parkinson's disease is the second most common neurodegenerative disease following
      Alzheimer's disease. As there is no biomarker or diagnostic test available for
      the diagnosis of Parkinson's disease, diagnosis of this disorder can be
      challenging. Parkinson's disease symptoms include both motor and non-motor
      symptoms. Non-motor symptoms may require special attention, such as the impulse
      control disorders that can be devastating to patients and their families. This
      Expert Review Supplement presents three cases that illustrate different aspects
      of Parkinson's disease, including diagnosis, non-motor symptoms, and treatment.

PMID- 19179949
TI  - Dental fluorosis: exposure, prevention and management.
AB  - Dental fluorosis is a developmental disturbance of dental enamel, caused by
      successive exposures to high concentrations of fluoride during tooth development,
      leading to enamel with lower mineral content and increased porosity. The severity
      of dental fluorosis depends on when and for how long the overexposure to fluoride
      occurs, the individual response, weight, degree of physical activity, nutritional
      factors and bone growth. The risk period for esthetic changes in permanent teeth
      is between 20 and 30 months of age. The recommended level for daily fluoride
      intake is 0.05 - 0.07 mg F/Kg/day, which is considered of great help in
      preventing dental caries, acting in remineralization. A daily intake above this
      safe level leads to an increased risk of dental fluorosis. Currently recommended
      procedures for diagnosis of fluorosis should discriminate between symmetrical and
      asymmetrical and/or discrete patterns of opaque defects. Fluorosis can be
      prevented by having an adequate knowledge of the fluoride sources, knowing how to
      manage this issue and therefore, avoid overexposure.

PMID- 19179950
TI  - Histopathological findings of pleomorphic adenomas of the salivary glands.
AB  - OBJECTIVES: To describe the histopathological features of pleomorphic adenoma
      (PA) with special reference to the epithelial and mesenchymal components. STUDY
      DESIGN: 189 PA were selected and classified as myxoid or stroma-rich, cellular or
      cell-rich and classic (balanced amount of epithelial and stromal components). The
      epithelial component was analyzed according to the presence of plasmacytoid,
      spindle, clear, squamous, basaloid, cubic, oncocytoid and mucous cells and the
      morphological pattern (trabecular, ductal, cystic and solid). The stromal
      component was analyzed according to the presence of myxoid, hyaline, chondroid or
      calcified tissue. RESULTS: Plasmacytoid cells were the most commonly found
      cellular type followed by fusiform and cuboidal cells. Trabeculae and duct-like
      structures were the most frequent patterns formed by the epithelial cells. Myxoid
      and chondroid stroma were the most frequently found mesenchymal-like tissue
      usually forming the so called myxochondroid stroma. CONCLUSION: The knowledge of
      the immense variety of cells, architectures and morphological characteristics
      present in PA of the salivary gland is essential for a correct diagnosis.

PMID- 19179951
TI  - Association between oral HSV-1 and survival in allogeneic hematopoietic stem cell
      transplanted patients.
AB  - INTRODUCTION: This study was designed to investigate the effect of oral HSV-1
      shedding on the survival of allogeneic hematopoietic stem cell transplanted (allo
      HSCT) patients. METHODS: One hundred nineteen allo-HSCT patients were included in
      the study and divided in three groups: before transplant, 100 days after
      transplant and 1 year of allo-HSCT. Healthy volunteers matched by age and gender
      were also selected. Oral swabs were performed and the nested PCR was used to
      detect HSV-1 presence in the oral mucosa. In statistical analysis, chi-square
      test was used to test the distribution of HSV1 shedding among the three groups.
      Time to death after allo-HSCT was displayed by means of the Kaplan-Meier method
      and the results were compared by the log-rank test. Cox proportional hazards
      multivariate model was used to evaluate the survival. RESULTS: We observed that
      HSV-1 shedding was similar at different points after allo-HSCT. However, HSV-1
      shedding before allo-HSCT was associated with worst survival rates after allo
      HSCT in multivariate analysis. CONCLUSION: Our data demonstrates that HSV-1
      shedding in oral mucosa before transplant is associated with worst survival rate
      of allo-HSCT patients.

PMID- 19179952
TI  - Multiple dens invaginatus, mulberry molar and conical teeth. Case report and
      genetic considerations.
AB  - Dens in dente, also known as dens invaginatus and dilated compound odontoma, is a
      malformation that can occur on primary, permanent, or supernumerary teeth that is
      characterized by a deep invagination of the surface of a crown or root covered
      with enamel. This abnormality in tooth morphology generally affect the maxillary
      lateral incisors but several cases of multiple dens invaginatus have been
      reported in the literature. A 15 year-old female patient is reported here
      presenting five dens invaginatus: four in the permanent mandibular incisors and
      one in the permanent, maxillary left central incisor, additionally the following
      dental findings were observed: a permanent mandibular left mulberry molar,
      molarization of some premolars, several microdontic conoid teeth, retention of
      five primary teeth, absence of several permanent teeth germs, a macrodontic molar
      with abnormal roots and several periapical radiolucencies associated to the dens
      invaginatus. There was no family history of similar dental findings to those
      observed in the patient. There are several genes that participate in the
      development of teeth, of those, the following five genes could be implicated as
      responsible or co-participators for some of the dental anomalies present in this
      patient: MSX1 (Muscle segment homeobox 1), DLX1 & DLX2 (Distal-less homeobox 1 &
      2 genes), PAX9 (Paired box gene) and PITX2 (Pituitary homeobox transciption
      factor 2).

PMID- 19179953
TI  - Pleomorphic adenoma of the palate in a child: a case report.
AB  - Salivary gland tumors are rare in children and the incidence differs from the
      adult counterpart. When salivary gland tumors do arise in children, they
      preferentially affect major salivary glands, but minor salivary gland tumors have
      also been reported. We reported the first case of palatal pleomorphic adenoma in
      a 13 year-old child from Thailand. She came to Sawanpracharak hospital with the
      chief complaint of a swelling at the left side of the palate. The oral mucosa
      covering the lesion was intact. Occlusal radiograph revealed no bony destruction.
      Incisional biopsy was performed on this patient. The biopsy showed several ducts
      which were lined by cuboidal cells. These ducts were surrounded by myoepithelial
      cells, some of which had the plasmacytoid appearance The patient was treated by
      wide local excision and no recurrence was observed 8 years after the surgery.
      Differential diagnoses of a palatal swelling in children and treatment of
      pleomorphic adenoma at the palate were also discussed.

PMID- 19179954
TI  - Biotechnological advances in neuro-electro-stimulation for the treatment of
      hyposalivation and xerostomia.
AB  - Treatment of xerostomia is a common clinical challenge in the oral medicine
      practice. Although some treatments have been used to improve the symptoms of
      xerostomia, none is completely satisfactory for the patients who suffer of this
      alteration. In the last years non-pharmacological treatments based on electro
      stimulation for the treatment of xerostomia have been developed. This review is
      aimed at presenting new developments for the treatment of xerostomia, applying
      neuro-electro-stimulation by miniaturized intra-oral electro-stimulators. These
      devices increase salivary secretion and improve symptoms of oral dryness. Their
      effect is obtained by means of stimulation of the lingual nerve, in whose
      proximity the electrodes of the apparatus are placed. The objective of this
      mechanism is both to directly stimulate the salivary glands controlled by that
      nerve and to enhance the salivary reflex. Clinical studies have been carried out
      that have demonstrated the wetting effect of the method described in this
      article.

PMID- 19179955
TI  - Pharmacological interactions of anti-inflammatory-analgesics in odontology.
AB  - In this second article we describe the more interesting pharmacological
      interactions in dental practice based on the prescription of analgesic narcotics,
      paracetamol and non-selective non-steroid anti-inflammatory drugs (NSAI) (which
      inhibit cyclooxigenase 1 -COX 1- and cyclooxigenase 2 -COX 2-) and selective
      NSAIs (COX 2 inhibitors). The importance of preventing the appearance of these
      pharmacological interactions is because these are medicaments prescribed daily in
      odontology for moderate pain treatment and inflammation in the oral cavity.
      Paracetamol can interact with warfarin and therefore care should be taken with
      chronic alcoholic patients. All NSAIs reduce renal blood flow and consequently
      are capable of reducing the efficacy of medicaments used for treating arterial
      hypertension, which act via a renal mechanism. Especial attention should be taken
      considering the risk of interaction between the antagonists of AT1 receptors of
      angiostensin II (ARAII) and the NSAIs.

PMID- 19179956
TI  - Synchronous unilateral parotid neoplasms. A case report.
AB  - The parotid gland is the most usual location of benign neoplasms affecting major
      salivary glands and quite often the recurrence of these tumours is noticed,
      specially in the case of pleomorphic adenoma. The occurrence of multiple tumours
      in the parotid glands is rare and the majority of these are multifocal Warthin's
      tumors (papillary cystadenoma lymphomatosum). The simultaneous development of
      tumours with different histological types is unusual and when it occurs, the most
      common combination is a pleomorphic adenoma and a Warthin's tumor. There are many
      articles about Multiple Parotid Tumors (MPT) but only a few of them are focused
      on unilateral synchronous benings tumors, being pleomorphic adenoma and Warthin's
      these tumors. The report describes a 55 year old female with a pleomorphic
      adenoma occurring synchronously with a Warthin's tumor within the superficial
      lobe of her left parotid gland.

PMID- 19179957
TI  - In vitro evaluation of the influence of the cortical bone on the primary
      stability of two implant systems.
AB  - AIMS: Immediate loading has become a predictable option for treatment, while one
      of the main requirements for its implementation is obtaining appropriate primary
      stability in implants. With that aim, conical implants are commercially
      available, since, according to specialized literature, they provide greater
      stability. One of the methods to measure implant stability which has evolved to
      further stages is resonance frequency analysis (RFA). In the present paper we
      attempt to evaluate the influence of the cortical bone on the primary stability
      of two implants of similar diameter and length. STUDY DESIGN: 15 fresh cow ribs
      were selected and six different implant beds were prepared in each. These
      preparations corresponded to two different implant systems: A Swiss Plus from
      Zimmer Dental and an Mk IV from Nobel Biocare. Two drilling protocols were used
      for soft bone, hard bone and bone without cortical. After preparing the beds, the
      implants were placed and implant primary stability was measured with the Osstell
      mentor. RESULTS: Higher ISQ (Implant Stability Quotient) values were observed for
      both implant systems when the cortical bone is maintained than when it is
      eliminated, the difference being statistically significant in the case of Mk IV
      implants. CONCLUSIONS: The results from this study show the importance of
      preserving cortical bone during drilling in order to obtain greater primary
      stability.

PMID- 19179958
TI  - Central giant cell lesion of mandible managed by intralesional triamcinolone
      injections. A report of two cases and literature review.
AB  - Central giant cell lesion (CGCL) is a benign lesion which has unpredictable
      biologic behaviour and is amenable to a plethora of treatment alternatives. We
      describe our experience in managing this lesion by intralesional triamcinolone.
      The mainstay of treatment of CGCL in our centre until now has been surgical
      curettage or resection. We chose two patients for this pilot endeavour at our
      hands. Case I is a 10 year old girl having CGCL of left side mandible. Case II is
      a 20 yr old man with CGCL affecting the left side posterior mandible. Both
      patients responded well to intralesional administration of triamcinolone
      acetonide (Kenacort-10) with no obvious recurrences to date. Successful
      application of this conservative drug therapy for managing CGCL can not only save
      the patient from a mutilating procedure but also has significant financial
      implications. The amount of triamcinolone injected ranged from 85 mg to 180 mg by
      5-6 injections at weekly intervals.

PMID- 19179959
TI  - Effects of dobutamine on gut mucosal nitric oxide production during endotoxic
      shock in rabbits.
AB  - BACKGROUND: Dobutamine is the agent of choice for increasing cardiac output
      during myocardial depression in humans with septic shock. Studies have shown that
      beta-adrenoceptor agonists influence nitric oxide generation, probably by
      modulating cyclic adenosine monophosphate. We investigated the effects of
      dobutamine on the systemic and luminal gut release of nitric oxide during
      endotoxic shock in rabbits. MATERIAL/METHODS: Twenty anesthetized and ventilated
      New Zealand rabbits received placebo or intravenous lipopolysaccharide with or
      without dobutamine (5 micro g/kg/min). Ultrasonic flow probes placed around the
      superior mesenteric artery and the abdominal aorta continuously estimated the
      flow. A segment from the ileum was isolated and perfused, and serum
      nitrate/nitrite levels were measured in the perfusate solution and the serum
      every hour. RESULTS: The mean arterial pressure decreased with statistical
      significance in the lipopolysaccharide group but not in the
      lipopolysaccharide/dobutamine group. The abdominal aortic flow decreased
      statistically significantly after lipopolysaccharide administration in both
      groups but recovered to baseline in the lipopolysaccharide/dobutamine group. The
      flow in the superior mesenteric artery was statistically significantly higher in
      the lipopolysaccharide/dobutamine group than in the lipopolysaccharide group at 2
      hours. The serum nitrate/nitrite levels were higher in the lipopolysaccharide
      group and lower in the lipopolysaccharide/dobutamine group than those in the
      control group. The gut luminal perfusate serum nitrate/nitrite level was higher
      in the lipopolysaccharide group than in the lipopolysaccharide/dobutamine group.
      CONCLUSIONS: Dobutamine can decrease total and intestinal nitric oxide production
      in vivo. Those effects seem to be inversely proportional to the changes in blood
      flow.

PMID- 19179960
TI  - The hemicellulose preparation, Natramune (PDS-2865), increases macrophage
      phagocytosis and nitric oxide production and increases circulating human
      lymphocytes levels.
AB  - BACKGROUND: Hemicellulose containing nutritional supplements demonstrate benefits
      to the immune system in vitro and in vivo. Here we show that Natramune (PDS-2865)
      stimulates phagocytosis, nitric oxide production and boosts viability in J774A.1
      murine machrophages. We also show that dietary supplementation with Natramune
      (PDS-2865) significantly increases the levels of circulating lymphocytes in human
      subjects. MATERIAL/METHODS: In order to measure the beneficial effects of
      Natramune (PDS-2865) on cells of the immune system, phagocytosis was measured by
      J774A.1 uptake of fluorescently labeled E. Coli bioparticles, nitric oxide
      production was measured by the formation of nitrite, and cell proliferation and
      viability was measured by NADH reduction of WST-8. The effect of Natramune (PDS
      2865) on human circulating leukocyte levels was measured in 18 volunteers after
      an 8 week regimen of two 250 mg doses daily after which blood was collected and
      blood cell number and types were counted. RESULTS: Natramune (PDS-2865)
      stimulated phagocytosis, nitric oxide production and promoted
      proliferation/viability in J774A.1 cells by 65%, 517%, and 155% respectively.
      Further, Natramune (PDS-2865) did boost human circulating total lymphocyte levels
      (18%) in a statistically significant manner and while all lymphocyte subtype
      levels also increased, the individual subtype increases were not statistically
      significant. CONCLUSIONS: Dietary supplementation with Natramune (PDS-2865)
      enhances immune system function and vitality.

PMID- 19179961
TI  - Prolonged survival and expression of neural markers by bone marrow-derived stem
      cells transplanted into brain lesions.
AB  - BACKGROUND: Bone marrow-derived stem cell transplantation is a potentially viable
      therapeutic option for the treatment of neurodegenerative disease.
      MATERIAL/METHODS: We have isolated bone marrow stem cells by standard method. We
      then evaluated the survival of rats' bone marrow mononuclear cells implanted in
      rats' brain. The cells were extracted from rats' femurs, and marked for
      monitoring purposes by adenoviral transduction with Green Fluorescent Protein
      (GFP). Labeled cells were implanted within the area of rats' striatum lesions
      that were induced a month earlier employing quinolinic acid-based method. The
      implants were phenotyped by monitoring CD34; CD38; CD45 and CD90 expression. Bone
      marrow stromal cells were extracted from rats' femurs and cultivated until
      monolayer bone marrow stromal cells were obtained. The ability of bone marrow
      stromal cells to express NGF and GDNF was evaluated by RT-PCR. RESULTS: Implanted
      cells survived for at least one month after transplantation and dispersed from
      the area of injection towards corpus callosum and brain cortex. Interestingly,
      passaged rat bone marrow stromal cells expressed NGF and GDNF mRNA. CONCLUSIONS:
      The bone marrow cells could be successfully transplanted to the brain either for
      the purpose of trans-differentiation, or for the expression of desired growth
      factors.

PMID- 19179962
TI  - A novel culturing system for fluid samples.
AB  - BACKGROUND: Large-volume culture methods for sterile body fluids employing
      automated blood-culture systems increase the recovery of microorganisms compared
      with traditional plate medium methods. However, in many instances a laboratory
      receives only small-volume samples. MATERIAL/METHODS: The URO-QUICK system (now
      HBandL), originally used to process urine samples, was evaluated for organism
      enrichment and determination of microbial count of fluid samples. Fluid specimens
      were also evaluated for their residual antimicrobial activity (RAA). The
      procedures were compared with results from a conventional culture procedure. The
      546 samples included 106 endotracheal aspirate, 63 bronchoalveolar lavage, 139
      sputum, 47 blood, 105 pleural fluid, 26 cerebrospinal fluids, and 41 peritoneal
      fluid samples as well as 19 other fluids including synovial fluid (n=5), ascitic
      fluid (n=9), fluids from the drainage of an infected central venous catheter
      (n=3), abdominal drainage fluid (n=1), and cholecystic fluid (n=1). RESULTS: The
      URO-QUICK system allowed the culture of an additional 44 samples (8%, p=0.007)
      compared with the traditional culturing method. The RAA test demonstrated good
      concordance with the reference method, showing specificity and positive
      predictive value of 100% for each, while the sensitivity and the negative
      predictive value were 67% and 76%, respectively. The microbial counts evaluated
      using the URO-QUICK system showed excellent agreement with traditional
      enumeration methods. CONCLUSIONS: The URO-QUICK system may well represent an
      excellent alternative to solid medium-based recovery and enumeration methods.

PMID- 19179963
TI  - The phenomenon of multifocality does not affect the biologic behavior of
      histologic prostate carcinoma.
AB  - BACKGROUND: The affect of multifocality on the biologic behavior of histologic
      prostate carcinoma is a controversial issue. The aim of this study was to
      determine if tumor multifocality influences the prognosis of patients with
      prostatic cancer. MATERIAL/METHODS: Samples consisted of 264 autopsy tissues from
      men older than 40 years of age and less than 98 years of age who died (between
      August 2002 and December 2005) of diseases other than clinically diagnosed
      prostate carcinoma. The entire prostate and seminal vesicles were sectioned,
      tinted, and fixed in acetic acid. Specimens were immersed in formalin, serial
      sectioned at a thickness of 4 mm, postfixed, resectioned at a thickness of 2 mm,
      dehydrated, cleared in xylene, and immersed in paraffin. Two expert pathologists
      examined the sections. RESULTS: Most latent carcinomas (61%) were multifocal and
      were composed of 2 or more foci. Ninety percent of distinct foci were found to
      originate from the peripheral zone. Multifocality was more common among larger
      prostates, and large tumors were almost exclusively multifocal. Half of these had
      a total volume less than 1 cm3 and a Gleason score of 2 to 6; there was a clear
      correlation between tumor volume and Gleason score. Heterogeneity of Gleason
      grade in multifocal tumors was proportional to the number of foci. No
      statistically significant difference was observed with respect to capsular
      penetration or perineural or vascular invasion of multifocal tumors compared to
      those of unifocal tumors. CONCLUSIONS: Despite relative heterogeneity, the
      biologic behavior of multifocal tumors is not different from that observed in
      unifocal histologic tumors.

PMID- 19179964
TI  - Influence of long-term exercise training on submaximal and peak aerobic capacity
      and locomotor economy in adult males with Down's syndrome.
AB  - BACKGROUND: The effect of exercise training on submaximal aerobic capacity and
      locomotor economy (LE) of Down's syndrome (DS) individuals has never been
      analyzed and their peak physiological adaptability to long-term physical
      conditioning is poorly understood. Thus the purpose of the present study was to
      determine whether DS males could improve their submaximal and peak aerobic
      capacity and LE after a 28-week training program. MATERIALS/METHODS: Twelve
      Caucasian DS males aged 34.5+/-7.0 years (range: 21-49) underwent a 28-week
      aerobic exercise intervention consisting of two 40-min sessions of ergometer
      conditioning per week. Body composition was assessed by anthropometric and
      bioelectrical impedance spectroscopic measurements. Pre- and post-training
      submaximal physiological response was determined by means of a 2.5-km/h treadmill
      flat-walk. Graded maximal exercise tests were performed to investigate the
      participants' peak exercise capacity. Multivariate analyses of variance were
      performed to explore the influence of training on the subjects' body composition
      and submaximal and peak aerobic capacity not. RESULTS: After training, the
      participants decreased their fat mass from 27.3+/-11.2 to 23.5+/-11.1% (p<0.01)
      and increased their absolute fat-free mass from 48.4+/-8.6 to 50.8+/-9.3 kg
      (p<0.01). There were no differences between pre- and post-training locomotor
      economy (LE). However, the subjects decreased their respiratory exchange ratio
      from 0.91+/-0.11 to 0.83+/-0.05 (p<0.05) while exercising at the same submaximal
      workload. Peak exercise capacity improved 27.8% following training (p<0.01).
      CONCLUSIONS: Despite improving body composition and peak cardiovascular fitness
      and lipidic oxidation during submaximal exercise, DS males were unable to modify
      their LE after 28 weeks of exercise intervention.

PMID- 19179965
TI  - Does the dynamicity of weight gain predict elements of metabolic syndrome?
      Differences in weight gain of hypertensive, diabetic, and obese elderly patients:
      a pilot study in primary care.
AB  - BACKGROUND: Some components of metabolic syndrome are measured in a medical
      setting; people check weight and height regularly. The aim was to analyze life
      long self-recorded data on patients' weight and compare them regarding
      hypertension, diabetes, and obesity. MATERIAL/METHODS: Retrospective data on
      weight and height in each life decade since 20 years of age and the decade prior
      to diagnosis were collected from 354 elderly people (159 men, 195 women) >60
      years of age. People with and without diabetes and/or hypertension were compared.
      RESULTS: Current mean weights were significantly higher in all groups than at 20
      years of age (p<0.001). Patients with normal body mass index (BMI: <25 kg/m2) had
      approximately the same weight as at 20, those currently overweight (BMI: 25-30
      kg/m2) had gained 14 kg (men) and 16 kg (women), and currently obese persons
      (BMI>30 kg/m2) more than 20 and 26 kg, respectively. Hypertensive persons weighed
      about the same in their twenties and currently as did controls. Diabetics started
      with higher weights. Men gained most between 20-30 years of age and women between
      20-40, both groups gaining significantly more in the decade before diagnosis than
      in other decades (p<0.05). Weight gain in the controls was more or less
      continual. CONCLUSIONS: Weight gain between 20-40 years of age may be an
      important factor in diabetes. Stable or at least limited and slow weight gain may
      be a preventive factor. Further evaluation is suggested in a wider population
      with more frequent and reliable data recording and international cooperation and
      comparison.

PMID- 19179966
TI  - The association between upper gastrointestinal lesions and high-sensitivity C
      reactive protein in coronary artery disease patients.
AB  - BACKGROUND: Although high-sensitivity C-reactive protein (hs-CRP) testing is not
      specific for coronary atherosclerosis, elevated hs-CRP is recently accepted as an
      independent predictor of future cardiovascular events. Also, a connection between
      upper gastrointestinal lesions (UGILs) and coronary artery disease (CAD) has been
      observed. The authors hypothesized that UGILs increase hs-CRP in CAD patients.
      MATERIAL/METHODS: One hundred fifty patients with stable CAD were enrolled in the
      study. Demographic and clinical variables and chronic medication used were
      gathered from a structured questionnaire. UGIL severity was determined by a
      modified Lanza score, H. pylori status by histology of the gastric mucosa, and
      the severity of CAD by a modified Gensini score. Independent correlation between
      hs-CRP and UGIL was tested by logistic regression analysis. RESULTS: The overall
      hs-CRP value was higher in patients with UGIL than in those with normal
      endoscopic results (8.14+/-4.53 mg/l vs. 4.64+/-3.06 mg/l, P<0.0001). hs-CRP
      level positively correlated with UGIL severity (r=0.434, P<0.0001). Correlation
      between UGIL and hs-CRP level remained significant after adjustment for coronary
      risk factors, medication used, CAD severity, and H. pylori status (standardized
      coefficient beta=1.272, P<0.0001). However, when hs-CRP level was used as a
      categorical variable, multivariate analysis revealed independent correlation only
      between UGIL and hs-CRP categories > or =6.1 mg/l. CONCLUSIONS: Elevated hs-CRP
      levels may be predictive of UGIL; thus endoscopy should be considered in CAD
      patients with elevated hs-CRP even with no dyspeptic symptoms. Because CRP plays
      an active role in atherothrombosis, UGILs with subsequent elevated CRP levels
      could increase cardiovascular risk in those patients.

PMID- 19179967
TI  - Incubation with DNase I inhibits tumor cell proliferation.
AB  - BACKGROUND: Deoxyribonuclease I (DNase-I) plays an important role in the
      elimination of damaged-, aging- or cancer cells. Various authors suggest that
      programmed cell death (PCD) is attenuated in cancer cells due to a reduced
      activity of DNase-I. MATERIAL AND METHODS: In this work, we evaluated cell
      viability (violet crystal stain), cell proliferation (tritiated thymidine) and
      DNA degradation of tumoral cells (Calu-1, SK-MES-1, HeLa, HEp-2, L-929) incubated
      with different concentrations of DNase I. PBMN cells and human fetal fibroblasts
      served as controls. RESULTS: Our results showed a >90% decrease in the viability
      of HeLa and HEp-2 cells, and >50%<90% decline in Calu-1, SK-MES-1 and L-929 cell
      viability, incubated with 9 mg/ml of DNase-I in comparison with control cells
      (p<0.05). The incorporation of [3H]thymidine showed a 50% decrease in tumoral
      cells. Control cells showed no significant differences. Tumor cell DNA
      degradation was observed after nuclease treatment, however the typical DNA
      ladder, characteristic of the apoptotic cell, was not observed. The morphology of
      some DNAse-I treated tumor cells suggested autoschizis CONCLUSION: Our results
      suggest that the use of a DNA nuclease might have some benefits in the treatment
      of cancer since it inhibits cell growth, probably by inducing autoschizis.

PMID- 19179969
TI  - Poor relation between Glasgow coma scale and survival after head injury.
AB  - BACKGROUND: Early indicators or predictors of outcome after head injury can
      affect clinical decision making and the choice of case-specific approaches to
      rehabilitation. MATERIAL/METHODS: A retrospective study of 60 patients with a
      head injury who had been admitted to a tertiary care hospital intensive care unit
      was undertaken to explore the possible correlations between the Glasgow Coma
      Scale (GCS) and outcome. The correlation among the GCS, GCS eye (GCS-E), GCS
      verbal (GCS-V), and GCS motor (GCS-M) components and outcome (survival or death)
      was assessed by constructing contingency Tables and performing the Pearson chi2
      and likelihood ratio tests. The statistical significance was set at a P value of
      0.05. RESULTS: The mean total GCS score was 6.39+/-0.554 (6.81+/-0.983 for
      survivors and 5.55+/-0.706 for nonsurvivors). The most frequent GCS score, which
      was 3 (61.67%), was followed by scores of 15 and 14 (10% and 6.7%, respectively).
      No correlation was found between outcome and the GCS, GCS-E, GCS-V, or GCS-M
      components. CONCLUSIONS: Our results suggest that the GCS has a limited
      predictive value of outcome in patients with a head injury, particularly if used
      as sole predictor or in patients with a mild-to-moderately severe injury.

PMID- 19179968
TI  - Peginterferon alfa-2b as monotherapy or in combination with lamivudine in
      patients with HBeAg-negative chronic hepatitis B: a randomised study.
AB  - BACKGROUND: The efficacy of pegylated interferon alfa-2b alone or in combination
      with lamivudine for the treatment of patients with hepatitis B e antigen (HBeAg)
      negative (-) chronic hepatitis B (CHB) is understudied. MATERIAL/METHODS: One
      hundred twenty-six patients with HBeAg(-)chronic hepatitis B received pegylated
      interferon alfa-2b > or =1.5 micro g/kg/wk for 48 weeks. Ninety of those subjects
      were randomly selected to receive concomitant treatment with lamivudine 100 mg/d.
      The coprimary end points were the subjects' virologic (hepatitis B virus
      deoxyribonucleic acid [HBV DNA] <60 IU/mL) and biochemical (normalization of
      alanine aminotransferase levels) responses 24 weeks after treatment cessation.
      RESULTS: The scores for necroinflammatory activity and fibrosis in patients
      randomly assigned to receive monotherapy were statistically significantly lower
      than those in patients receiving combination therapy. HBV DNA levels were
      statistically significantly higher and alanine aminotransferase levels were
      statistically significantly lower in patients receiving monotherapy than in those
      receiving combination therapy. Virologic responses in the monotherapy and
      combination therapy groups were similar at weeks 48 and 72 (59.1 vs 42.9%). The
      biochemical response at week 72 was also similar in the treatment groups. The
      results of multiple regression analysis showed that the virologic response at
      week 72 was independently correlated with the pegylated interferon alfa-2b dose
      and that the biochemical response was independently correlated with
      necroinflammatory activity, the pegylated interferon alfa-2b dose, and lamivudine
      therapy. CONCLUSIONS: These data support the use of pegylated interferon alfa-2b
      in patients with HBeAg(-) chronic hepatitis B; however, the concomitant use of
      lamivudine produced no additional clinical benefit.

PMID- 19179970
TI  - Lysozyme and microbiota in relation to gingivitis and periodontitis.
AB  - BACKGROUND: The aim of this study was to investigate associations between the
      immune component of the oral cavity, lysozyme, in gingival crevicular fluid and
      unstimulated saliva, and colonization dynamics of periodontopathogenic bacteria
      from supra- and subgingival plaque samples in patients with gingivitis or
      periodontitis. MATERIAL/METHODS: Lysozyme in crevicular fluid and unstimulated
      saliva, and bacteria in supra- and subgingival plaque samples were assessed in 84
      samples from 28 patients with gingivitis, 96 samples from 32 patients with
      periodontitis, and 72 samples from 24 donors with intact periodontium and free of
      internal disease. Lysozyme activity was determined spectrophotometrically. The
      micro-IDent plus assay was used to detect 6 periodontopathogenic bacteria plaque
      samples. RESULTS: Lysozyme activity in crevicular fluid in the gingivitis and
      periodontitis groups was significantly greater than that in the donor group, but
      lysozyme activity in unstimulated saliva was less than that in the donor group.
      Peptostreptococcus micros, Fusobacterium periodontium and Campylobacter rectus
      were predominant in subgingival plaque samples in the periodontitis group
      compared to the donor group (P<0.001), and Eubacterium nodatum and Eikenella
      corrodens were predominant in the gingivitis group compared to the donor group
      (P<0.001). CONCLUSIONS: Lysozyme activity in crevicular fluid and in unstimulated
      saliva correlated with periodontal pocket depth in donors and in patients with
      gingivitis or periodontitis (specificity and sensitivity were both 100%). These
      findings indicate that infection with P. micros, F. periodontium, E. nodatum, E.
      corrodens, and C. rectus may be an important indicator of inflammatory
      periodontal disease development.

PMID- 19179971
TI  - Predicting time to healing by anatomical assessment of venous pathology.
AB  - BACKGROUND: The aim of the study was to assess the clinical effectiveness of
      multilayer compression in aspect of anatomical site of venous pathology and
      ulcers. MATERIAL/METHODS: The study was conducted between 2000 and 2006 among 112
      patients with 121 ulcers treated in the Venous Ulcer Outpatient Clinic of the
      Chair and Clinic of Surgery, Biziel Hospital in Bydgoszcz, Poland. Patients
      between 31 and 89 years old (mean age - 63.6 years, median 65) were randomized
      into two groups treated with two- and four-layer compression system. Healing
      process dynamics were assessed by planimetry. Maximum period of observation was
      48 weeks. RESULTS: The longest mean time of ulcer healing and the highest values
      of cumulated indicator of unhealed ulcers were observed among patients with
      simultaneous insufficiency of two venous systems - superficial and deep
      (p=0.0034, test log-rank) and among patients with insufficiency of deep,
      superficial and perforating venous system (p=0.0001, test log-rank).
      Significantly longer mean healing time was characteristic for localization on the
      back calf region (p=0.01, test log-rank). Dynamics of healing of ulcers treated
      by two- and four-layer systems were compared. CONCLUSIONS: Anatomical
      localization of venous pathology and ulcer localization were found as important
      prognostic factors; longer healing time and lower probability of healing was
      observed among patients with deep venous insufficiency and when the ulcer was
      localized in the atypical back calf region. No differences of healing time
      between groups in aspect of used system were showed.

PMID- 19179972
TI  - Duration of untreated psychosis and proton magnetic resonance spectroscopy (1H
      MRS) findings in first-episode schizophrenia.
AB  - BACKGROUND: The duration of untreated psychosis (DUP) is a factor associated with
      the natural course of schizophrenia and an independent predictor of treatment
      outcome. Recent studies focus on the effects of DUP on the functioning of the
      nervous system, but the findings are inconsistent. As proton magnetic resonance
      spectroscopy (1H-MRS) enables the assessment of signals from chemical compounds
      in vivo, it seems a useful tool to explore this problem. MATERIAL/METHODS: In
      this study the relationships between DUP and 1H-MRS measurements were
      investigated. Thirty patients with first-episode schizophrenia and 19 controls
      were examined. Median DUP was 10 weeks. Voxels were positioned in the following
      regions of interest: the left frontal lobe, left temporal lobe, and left
      thalamus. The ratios of N-acetylaspartate (NAA), choline-containing compounds
      (Cho), myoinositol (mI), and glutamate/glutamine/GABA complex (Glx) to creatine
      (Cr) and the non-suppressed water signal were determined. RESULTS: There were no
      significant differences between the whole group of patients and healthy subjects
      for the analyzed metabolite ratios in any region of interest. No differences were
      found between the groups of patients with short and long DUP and controls. No
      significant correlation was observed between DUP and metabolite ratios.
      CONCLUSIONS: The results of the study may suggest that the relatively short DUP
      does not influence brain metabolism in first-episode schizophrenia.

PMID- 19179974
TI  - Acute acalculous cholecystitis with pericholecystitis in a patient with Epstein
      Barr Virus infectious mononucleosis.
AB  - BACKGROUND: Acute acalculous cholecystitis is a rare complication of Epstein-Barr
      virus mononucleosis and involves thickening of the gallbladder wall. CASE REPORT:
      We describe the case of a 22-year-old woman with acute acalculous cholecystitis
      and pericholecystitis associated with Epstein-Barr virus primary infection.
      Surgical intervention was not performed, even though gallbladder perforation was
      suspected. The patient was treated conservatively with careful monitoring,
      including repeated ultrasonographic examinations. CONCLUSIONS: Epstein-Barr virus
      infections are usually self-limited, and surgical treatment of acute acalculous
      cholecystitis should only be considered when the ultrasonographic criteria
      persist on follow-up examinations or when they deteriorate. This is the first
      report of a severe course of acute acalculous cholecystitis with suspected
      gallbladder perforation associated with infectious mononucleosis.

PMID- 19179973
TI  - Meningeal relapse in a case of B acute lymphoblastic leukemia: the role of CD56
      expression.
AB  - BACKGROUND: Blasts from B acute lymphoblastic leukemia (B-ALL) may express CD56
      in about 10% of cases. The presence of this marker at diagnosis is associated
      with an increased risk of meningeal relapse. A case is described of B-ALL which
      was CD56 negative at diagnosis, and expressed this marker when isolated meningeal
      relapse was diagnosed. CASE REPORT: A 53-year-old female patient presented with
      neurological symptoms during maintenance therapy for B-ALL. Peripheral blood,
      bone marrow, and cerebrospinal fluid (CSF) were subjected to both morphological
      and flow cytometric analyses. The latter was carried out by a wide routine panel
      of MoAbs which was the same as the one at diagnosis and included CD56. Isolated
      meningeal relapse was diagnosed since blast cell infiltration was detected in the
      CSF, but not in the peripheral blood and bone marrow samples. Blast cells showed
      an immunological phenotype similar to that at diagnosis (cyCD79a+, CD79b+, CD19+,
      CD22+, CD34+, CD10+, CD20+), but characterized by the acquisition of CD56 on the
      surfaces of more than 90% of cells. CONCLUSIONS: This case shows that CD56 can be
      expressed at relapse of B-ALL and that its presence likely enables leukemic cell
      binding to the central nervous system (CNS). This phenomenon may be responsible
      for the isolated CNS relapse diagnosed in this patient.

PMID- 19179975
TI  - Fournier's gangrene: historical survey, current status, and case description.
AB  - BACKGROUND: The first-documented clinical picture of the disease was made by
      Fournier in 1883. Its epidemiology has changed and is much different from the
      original. It is infectious in its etiology, affecting mostly men between 50 and
      60 years of age. Predisposing factors include diabetes, neoplasms, chronic
      glucocorticoid therapy, immune-compromise, chemo- and radiotherapy,
      immunosuppression, Crohn's disease, and alcohol abuse. High mortality results
      from the rapid progress of the disease, leading to quick development of septic
      shock and multi-organ failure. Most important in the treatment of Fournier's
      gangrene are surgical debridement of the wound, fascia incision and drainage of
      necrotic lesion, and intravenous antibiotic therapy. The typical picture of the
      disease might be hidden by concomitant disease. CASE REPORT: A case of Fournier's
      gangrene in an 81-year-old woman with concomitant neurologic complications,
      hypertension, cardiomyopathy, and chronic obstructed pulmonary disease is
      described. Three days after the suspected diagnosis, the decision was made to
      fully remove the necrotic tissue surgically. Despite all the efforts of the
      medical team, the patient died 14 days after being diagnosed with Fournier
      gangrene. The immediate cause of death was septic shock. CONCLUSIONS: In the
      early stages of the disease, before necrotic lesions occur, a final diagnosis
      might be difficult. In the present case, death was caused by the patient's
      advanced age, simultaneously appearing symptoms, and late surgical intervention,
      but mostly by lung failure.

PMID- 19179976
TI  - Osteoactivin bioinformatic analysis: prediction of novel functions, structural
      features, and modes of action.
AB  - BACKGROUND: The initial identification of osteoactivin (OA) came from studies
      using an animal model of osteopetrosis in rats. Several recent studies suggested
      roles for OA in osteoblast differentiation, fibroblast differentiation, cancer
      metastasis, and attenuation of muscle, liver, and kidney injury-induced
      degeneration. MATERIAL/METHODS: Several bioinformatic tools were utilized,
      including ArrayExpress, Pfam, SMART, Prosite, ELM, ProFun, PFP, Consensus
      Secondary Structure Prediction server, and Geno3D. RESULTS: 1) Novel OA functions
      and biological roles were predicted, including roles in cell envelope formation,
      enzyme activities, immune response activities, negative regulation of B-cell
      activation, antigen processing, heme catabolism, endothelial cell
      differentiation, establishment of protein localization, melanin biosynthesis from
      tyrosine, regulation of blood pressure, response to light, and lung development.
      2) Novel OA functional motifs were predicted, including N-Arg dibasic convertase
      cleavage site, NEC1/NEC2 cleavage site, peptide C-terminal amidation,
      glycosaminoglycan attachment site, and generic motif for N-glycosylation, and
      substrate recognition sites that interact with different cytosolic proteins,
      including cyclin, MAPK, Class III PDZ domains, GSK3, phosphorylase kinase,
      tyrosine-based sorting signal, and internalization signal. 3) OA's secondary and
      tertiary structural models were predicted. CONCLUSIONS: bioinformatic structural
      analysis predicted that OA has three major structural domains: two helical
      structures on its termini and beta sheets as a sandwich-like structure in the
      middle. Several functional motifs have been predicted suggesting different modes
      for OA functions (receptor, ligand, and enzyme). Combined data from OA's
      expression array and function prediction data suggest that OA might play a role
      in several pathologic conditions, including hypertension, diabetes, and immune
      system disorders.

PMID- 19179978
TI  - Burden and etiology of community-acquired bacterial meningitis in a hospital in
      Eastern Saudi Arabia: 1993-2005.
AB  - BACKGROUND: In the Middle East, some evidence suggests marked declines in cases
      of H. influenzae type b infection where conjugate vaccines were introduced. This
      study examined the causative agents of bacterial meningitis in Saudi Arabia over
      time in both children and adults. MATERIAL/METHODS: From January 1993 to December
      2005 there was a total 179 cases of meningitis, of which 63 (35.2%) were
      bacterial meningitis, 37 (20.7%) partially treated, and 79 (44.1%) which were
      considered viral in origin. RESULTS: The annual incidence rates of bacterial
      meningitis were 0.48-2.8 per 100,000 population, with an overall insignificant
      decline over the study period (P=0.8). There were 37 males and 26 females (ratio:
      1.4:1) with an age range of <1 month to 72 years and a median age of 2 years. Of
      the total number of patients, 22.2% (n=14) were 1-23 months and 39.7% (n=25) were
      2-18 years of age. The causative organisms were Streptococcus pneumoniae (35%,
      n=22), Haemophilus influenzae type b (22.2%, n=14), Neisseria meningitides
      (15.9%, n=10), Group B streptococci (7.9%, n=5), and 19% (n=12) were other
      organisms. Of H. influenzae type b cases, 57% (n=8) were in children one year of
      age and 78.6% (n=11) were in the years 1993-1999. The rates of H. influenzae
      meningitis cases in the periods of 1993-1999 and 2000-2005 were 4.2 and 1.2 per
      100,000 population, respectively. CONCLUSIONS: There was a drop in the number of
      cases of H. influenzae type b, but it was not statistically significant, and
      might be related to the small sample size.

PMID- 19179977
TI  - Prognostic relevance of cyclin E expression in operable breast cancer.
AB  - BACKGROUND: Cyclin E is an important regulator of cell-cycle progression. High
      levels of cyclin E protein in breast cancer have been reported in association
      with higher disease stage, poor histological differentiation of tumor, and lack
      of steroid receptors. Data concerning the prognostic relevance of cyclin E
      expression in breast cancer are conflicting. The aim of this retrospective study
      was to evaluate the prognostic relevance of cyclin E expression assessed by
      immunohistochemistry in patients with operable invasive ductal breast cancer.
      MATERIAL/METHODS: The expression of cyclin E was analyzed by immunostaining in
      174 women with breast cancer after radical mastectomy with a median follow-up
      period of 58 months. Tumor samples were judged to be negative (<2%) or positive
      (> or =2%) according to the percentage of cells showing the nuclear staining
      pattern. Ninety-nine (56.9%) tumor samples were regarded as cyclin E-positive.
      RESULTS: Positive staining for cyclin E determined poor prognosis compared with
      cyclin E-negative patients in all cases (five-year cancer-specific survival rate
      of 64.5 vs. 84.5%, p=0.005), in the node-positive group (50.9 vs. 82.1%,
      p=0.008), and in patients treated with adjuvant chemotherapy (71.0 vs. 96.6%,
      p=0.008). In a multivariate analysis, high expression of cyclin E was associated
      with a higher risk of death in the node-positive group (hazard ratio: 3.2, 95%CI:
      1.3-8.2, p=0.015). CONCLUSIONS: It was demonstrated that a high expression of
      cyclin E measured by immunohistochemistry was a significant factor of poor
      prognosis, especially in the node-positive group.

PMID- 19179979
TI  - Magnesium sulfate reduces postoperative morphine requirement after remifentanil
      based anesthesia.
AB  - BACKGROUND: The aim was to investigate the effect of magnesium sulfate on
      postoperative pain and analgesic consumption after remifentanil-based anesthesia.
      MATERIAL/METHODS: Forty women 18 to 65 years old were enrolled in this
      prospective, randomized, double-blinded clinical study. The study solutions were
      randomly preoperatively prepared for groups M (magnesium) and R (normal saline).
      A bolus of 0.2 ml/kg of study solution (30 mg/kg magnesium or saline) was given
      before induction of anesthesia and infusion was started at a rate of 3.3 ml/h
      (500 mg/h magnesium or saline). A 1 microg/kg loading dose of remifentanil
      following infusion was started at a rate of 0.25 micro g/kg/min, subsequently
      increasing stepwise by 0.05 micro g/kg/min increments if insufficient anesthesia
      was suspected. All postoperative outcome data were collected by an
      anesthesiologist who was blinded to the anesthetic regimen. Pain intensity using
      a visual analogue scale (VAS) was recorded for 24 hours postoperatively. RESULTS:
      Hemodynamic and respiratory variables such as diastolic and systolic blood
      pressure, heart rate, and oxygen saturation were similar in both groups. The mean
      intraoperative remifentanil consumption in groups M and R was similar. The VAS
      score was significantly lower in the magnesium group at 15 and 30 minutes
      postoperatively. Total morphine consumption was significantly lower in the
      magnesium group than in the remifentanil-alone group. CONCLUSIONS: It was
      concluded that magnesium sulfate decreased the postoperative morphine requirement
      when remifentanil was used for intraoperative analgesia.

PMID- 19179980
TI  - From the basics to application of cell therapy, a steppingstone to the conquest
      of neurodegeneration: a meeting report.
AB  - The annual meeting of the American Society for Neural Therapy and Repair (ASNTR)
      showcases the latest research trends in neurodegenerative disease and the related
      medical regenerative science. The 2008 ASNTR meeting covered a variety of
      different topics ranging from basic research to exploration of currently unknown
      pathogenesis and mechanisms for specific neurodegenerative disease such as
      Parkinson's disease, Alzheimer's disease, or stroke. This included studies to
      characterize stem cells, such as neural stem cells, embryonic stem cells, bone
      marrow mesenchymal stem cells, and human umbilical cord blood cells, for
      transplantation and the conditions necessary to maximize the efficacy of
      endogenous and exogenous stem cells, such as isolation, purification,
      differentiation, and migration. Moreover, a number of studies looked at methods
      for more advanced application of transplantation of cells or specific factors,
      through tissue engineering or manipulation beyond simple injection. Finally, well
      known or previously un-known dietary supplementation or pharmacological materials
      that can affect the nervous system positively or negatively, were also important
      topics.

PMID- 19179981
TI  - Genetically transformed world records: a reality or in the sphere of fantasy?
AB  - The disclosure of repeated cases of athletes who abuse performance-enhancing
      drugs is an ordinary phenomenon in the athletic community. In addition, the
      completion of sequencing of the human genome and the unprecedented advances in
      molecular biology have enabled the progression from traditional drug enhancement
      to hypothetical (at present) gene transfer. Scientific, sports, and antidoping
      authorities fear that gene doping will be the next major challenge. The misuse of
      gene therapy to improve athletic ability, which is commonly referred to as "gene
      doping," represents a practice as dangerous and unethical as any type of
      conventional doping. However, gene doping appears to be more attractive than
      traditional forms of doping because it is still undetectable and thus much less
      preventable. This review focuses on gene doping, the risks involved, and the
      ethical issues that emerge. It also discusses the possible strategies that can be
      used to detect this new form of doping.

PMID- 19179982
TI  - Venous catheter microbiological monitoring. Necessity or a habit?
AB  - BACKGROUND: Usefulness and economic aspects of microbiological analysis of
      central venous catheter (CVC) tips in diagnosis of the catheter-related
      bloodstream infection (CRBSI). MATERIAL/METHODS: Retrospective study of an adult
      intensive care unit in a university hospital. Catheter removal was performed when
      the clinical state of the patient indicated that the catheter could be the source
      of infection or inflammation was observed at the puncture site. RESULTS: We
      microbiologically studied 238 CVC tips according to the Maki method and 723 blood
      samples from 120 septic patients treated during a 21-month period (32.9% of all
      patients treated in this time period). In 115 cases (48.4%), the tips were
      positive. Bacteremia was ascertained in 181 blood samples (24.1%), and 168
      samples were collected at the time of CVC removal. In blood samples taken from 20
      patients (3% of total blood samples), 25 cases of the same pathogens were
      isolated from CVC tips. In 12 cases, pathogens found in blood and CVC tips were
      also cultured in other places. In 13 cases (5.5% of tips), CVCs were the source
      of CRBSI. Positive predictive value (PPV) and negative predictive value reached
      11% and 91%, respectively. The total cost of CVC tip monitoring was about 4000
      euro. CONCLUSIONS: Our data support the hypothesis that colonization of CVC is
      rarely responsible for CRBSI. Relatively low PPV renders tips culture useless as
      a method of diagnosing CRBSI. Based on these results, the routine microbiological
      monitoring of CVC tips was discontinued to reduce the cost of treatment.

PMID- 19179983
TI  - The journal impact factor: how to interpret its true value and importance.
AB  - In 1955, Garfield suggested that the number of references could be used to
      measure the "impact" of a journal, but the term "impact factor" was introduced in
      1963 by Garfield and Sher. The primary goal of impact factor analysis was to
      improve the management of library journal collections. Single-parameter
      measurements of the quality of a journal article have become increasingly popular
      as a substitute for scientific quality. The simplicity of its counting system and
      convenience of its use are significant benefits. Probably for these reasons,
      funding bodies, academic authorities, and some governments began using the impact
      factor to guide decisions about allocating grants, awarding appointments and
      academic degrees, and defining scientific policy. The journal impact factor,
      which is often recognized as a symbol of scientific prestige and relevance, can
      be, however, greatly influenced by the type of medical article (review vs
      original work), clinical specialty, and research. The true value and implications
      of the journal impact factor (JIF) are important to understand. It is critical to
      remember that JIF can be used only to evaluate journals. All comparisons should
      include only journals and never individuals or departments. Only similar journals
      (particularly those dedicated to the same scientific specialty) must be compared,
      because the value of the impact factor varies greatly by discipline.

PMID- 19179984
TI  - The "polyvascular patient." Foreword.

PMID- 19179985
TI  - Current trends in cardiovascular therapy.

PMID- 19179986
TI  - Cardiac CT for CAD. Do we still need angiography?
AB  - Recent technological advances have led to a substantial increase in image quality
      in multi-detector computed tomography (MDCT). Over the last few years, there has
      been significant interest and controversy about the clinical application of CT
      angiography for the evaluation of the coronary anatomy in patients with suspected
      coronary artery disease (CAD). Unlike invasive coronary angiography, CT coronary
      angiography provides both visualization of the lumen and the coronary vessel
      wall. Calcified plaques can be detected without contrast administration and
      easily quantified. MDCT has largely replaced electron beam computerized
      tomography for calcium scoring. Growing evidence suggests that measurement of
      coronary calcium may be particularly valuable in therapy decisions for
      asymptomatic patients with an intermediate risk of coronary events. Recent
      studies have also shown an association between non-calcified coronary plaques and
      acute coronary syndromes in patients with stable angina. Contrast-enhanced CT
      coronary angiography provides a non-invasive alternative to intravascular
      ultrasound to evaluate coronary plaque morphology and severity. Contrast-enhanced
      CT has been extensively validated for the detection of coronary artery stenosis
      in symptomatic patients with known or suspected CAD. The number of non-evaluable
      cases has been reduced below 10% with the newest generation scanners. Although
      there is considerable enthusiasm, many doubts remain about the appropriate
      clinical indications of CT coronary angiography, even though most experts believe
      that the high negative predictive value of CT coronary angiography makes this
      test ideal for establishing or excluding coronary artery disease in patients with
      low-intermediate probability.

PMID- 19179987
TI  - Indications for coronary artery bypass grafting in 2009: what is left to surgery.
AB  - Coronary artery bypass grafting (CABG) remains the most common procedure
      performed by cardiac surgeons, yet it is clear that the landscape of coronary
      intervention is constantly changing as new technology is introduced and data from
      countless studies continues to be published. However, no single study will be
      able to clearly define the indications for surgical versus percutaneous
      revascularization in every clinical scenario given the complexity of this disease
      as well as that of the patients it afflicts. Moreover, the significant
      improvements in percutaneous therapy, medical therapy management, perioperative
      care and secondary prevention after revascularization have decreased the
      morbidity and mortality of coronary artery disease making comparison between
      therapies far more difficult. Based on the available literature to date, surgical
      revascularization (CABG) provides significant benefit in certain patient
      populations; particularly those with comorbid conditions (for example diabetes,
      left ventricular [LV] dysfunction) and with more severe disease (for example left
      main, three-vessel). The goal of this article is to outline the current for
      surgical revascularization (CABG) understanding that coronary artery disease will
      continue be an important cause of morbidity and mortality and further study and
      re-evaluation of these recommendations will likely be necessary as time goes on.

PMID- 19179988
TI  - Current status in cervical carotid artery stent placement.
AB  - Based upon recent and old medical literature, with the exception of high surgical
      risk symptomatic patients, there remains much debate on how to manage
      extracranial carotid arterial disease, whether by surgical or endovascular
      intervention or by medical therapy alone. A review of the various global current
      carotid artery stent and endarterectomy registries and trials was performed
      incorporating more than 14,000 patients who have received carotid stents. There
      is substantial evidence supporting the benefit of carotid artery stenting (CAS)
      for the high anatomic risk population. Complication rates with symptomatic
      patients, including octogenarians, continue to show trend towards improvement as
      operators gain experience. The results are limited for standard risk carotid
      stenting for symptomatic patients though results with recent trials are pending
      but will probably show equivalence with endarterectomy. The asymptomatic patient
      population remains controversial: there is a small but reproducible benefit for
      revascularization. Long term (1-3 years) neurological results are now being
      reported for the major registries and trials. Analysis of target lesion
      revascularization, stroke and death rates of carotid stenting is comparable or
      better than rates for endarterectomy. Carotid artery stent placement has met the
      CMS targets 3% for MAE for asymptomatic patients and 6% for symptomatic patients
      with numerous registries and trials. CAS has also proven outcomes at 3 years with
      restenosis rates and stroke-free rates comparable or better than CEA. CAS
      provides an option for patients not suited for medical therapy and who were high
      risk for CEA, especially for those symptomatic patients. It is still
      controversial with the role of stenting asymptomatic patients as well as for
      octogenarians. However, forthcoming trials will be helpful in providing more
      insight. Despite questionable studies and bad press, carotid stenting in the
      right hands with good patient selection is an excellent procedure. Finally, it is
      important to remember, carotid stenting is still in its early development and
      will only get better.

PMID- 19179989
TI  - Carotid artery stenosis: what is left to surgery.
AB  - While carotid angioplasty and stenting has been clearly established as a
      minimally invasive alternative to endarterectomy for patients with carotid
      occlusive disease, its indications continue to evolve, being refined as more
      controlled data of large studies are being accumulated. The purpose of this
      article is to review the current evidence supporting the application of either
      technique in certain subsets of patients, and the relative contraindications for
      their use.

PMID- 19179990
TI  - Safety and effectiveness of combining carotid artery stenting with cardiac
      surgery: preliminary results of a single-center experience.
AB  - AIM: Optimal strategy (staged or combined) for the treatment of patients with
      concurrent severe carotid and cardiac disease is still controversial. Moreover,
      carotid artery stenting (CAS), has become a valid alternative to carotid
      endarterectomy (CEA) and has been proposed for the treatment of cardiac patients.
      The authors report the preliminary results of a new therapeutic strategy
      consisting in combined CAS and cardiac surgery. METHODS: An initial series of 22
      patients underwent combined CAS and cardiac surgery in the same operating room
      and under general anesthesia. All filter-protected CAS procedures were performed
      under only heparin and aspirin. A cervical approach (3-cm cervicotomy) was used
      in patients with documented vessel tortuosity or severe aorto-iliac occlusive
      arteriopathy. In all the other cases a femoral access was used. A double
      antiplatelet regimen was initiated in the early postoperative period, once major
      bleedings were excluded. RESULTS: Among the 22 patients who underwent this
      combined procedure, no deaths, no myocardial infarctions and one controlateral
      stroke (overall complication rate: 4.5%) were observed. This stroke was observed
      after transcervical CAS, coronary artery bypass and mitral valve replacement. No
      major postoperative bleedings nor stent thrombosis were observed. CONCLUSIONS:
      Combined carotid stenting and cardiac surgery, performed in the same operating
      room under only heparin and aspirin, seems a safe and effective strategy for the
      treatment of patients with concomitant carotid and cardiac disease.

PMID- 19179991
TI  - Revascularization strategy in patients with severe concurrent severe carotid and
      coronary artery disease: ''failure to move forward is reason to regress''.
AB  - In the absence of randomized trials, the optimal management of patients with
      concomitant carotid and coronary artery disease remains disputable. The initial
      studies of combined or staged carotid endarterectomy in these patients were
      conceived in an attempt to reduce perioperative mortality. Although encouraging
      results have been reported with combined carotid endarterectomy and cardiac
      surgery, this combination requires long operative times and remains a surgical
      challenge. Recent studies have shown that carotid angioplasty and stenting prior
      to cardiac surgery is a feasible and effective minimal invasive technique.
      However, the effect of carotid stenting on the incidence of death and stroke
      after cardiac surgery is indistinct. Carotid stenting followed by cardiac surgery
      may provide a valuable treatment for patients with combined carotid and cardiac
      disease. The high rate of freedom from death and stroke during follow-up supports
      the long-term durability of this strategy. In the present review, we highlight
      the available data on carotid stenting and cardiac surgery.

PMID- 19179992
TI  - Stroke after coronary artery bypass grafting. Is there place for a stroke-risk
      stratification model?
AB  - AIM: Preoperative carotid screening is common in the prevention of perioperative
      stroke. The authors describe our experience with selective screening of patients
      with a recent (<1 year) neurological event. Because many variables are related
      with the development of perioperative stroke we additionally evaluate the value
      of a stroke-risk stratification model. METHODS: Of 1 442 isolated myocardial
      revascularizations performed between January 2002 and December 2005, 118 patients
      had a history of preoperative stroke. Twenty-four patients had a recent stroke.
      In 5/24 patients duplex revealed significant stenosis of the internal carotid
      artery, which was treated prophylactically. RESULTS: Eleven patients (0.83%)
      developed a perioperative stroke. Three patients recovered completely during
      hospital stay, three died related to their stroke. Of the other 94 patients with
      a history of stroke, 5 had a stroke, none of them had a significant stenosis of
      the carotid artery. Of the 1,224 patients without a history of stroke, 6
      developed a perioperative stroke. Three of them had a significant carotid artery
      stenosis, however in two patients stroke deficit was on the ipsilateral side and
      the third patient had a transient ischemic attack. All eleven patients had a
      calculated stroke risk of 3 or higher corresponding with a expected risk of at
      least 0.9%. CONCLUSIONS: With the used protocol, in the described patient
      population, perioperative stroke incidence is low. on the other hand, the
      complexity of the mechanism of perioperative stroke is confirmed and the use of a
      stroke-risk stratification model seems us justified for a better identification
      of patients at risk.

PMID- 19179993
TI  - Does the risk of post-CABG stroke merit staged or synchronous reconstruction in
      patients with symptomatic or asymptomatic carotid disease?
AB  - The management of patients undergoing coronary artery bypass grafting (CABG) who
      are found to have co-existent carotid artery disease remains controversial.
      Management options include performing an isolated CABG, synchronous carotid
      endarterectomy (CEA) plus CABG, staged CEA-CABG, reverse staged CABG-CEA,
      synchronous CEA+CABG off bypass (OFFCAB) and staged carotid angioplasty with
      stenting (CAS) followed by CABG. For any of these combined or staged
      interventions to be clinically effective, the following conditions must be met;
      (1) CABG must be a proven intervention for ischaemic heart disease, (2) stroke
      must be an important cause of peri-operative morbidity and mortality, (3) the
      incidence of post-CABG stroke must be high enough to justify a programme of
      prevention, (4) carotid disease must be an important cause of post-CABG stroke,
      (5) CEA (CAS) must be a proven intervention in carotid artery disease and (6)
      prophylactic CEA (CAS) should reduce the risk of post-CABG stroke. This paper
      reviews the literature and concludes that conditions 1, 2 and 5 are met and that
      condition 3 can be achieved provided high risk' subgroups are targeted. However,
      there is limited evidence to support the contention that carotid disease is a
      major cause of post-CABG stroke and any potential benefit conferred by
      prophylactic intervention (whether by CAS or CEA) may be offset by the relatively
      high procedural risks observed in systematic reviews. Prophylactic carotid
      intervention is justified in CABG patients with a prior history of stroke or TIA.
      Debate continues about the role of CEA (CAS) in patients with asymptomatic
      bilateral carotid disease, but there seems to be little evidence to justify
      prophylactic CEA or CAS in CABG patients with unilateral asymptomatic carotid
      disease.

PMID- 19179994
TI  - Off-pump concomitant coronary revascularization and carotid endarterectomy.
AB  - Combined coronary artery bypass surgery and carotid endarterectomy is a
      controversial topic. With the recent revival of off-pump coronary artery surgery
      the question remains very actual. The aim of this study was to present a
      comprehensive review of the topic focusing on current strategies, including off
      pump coronary artery bypass surgery.

PMID- 19179995
TI  - Coronary artery disease in patients with abdominal aortic aneurysm: a review
      article.
AB  - Abdominal aortic aneurysms (AAA) and coronary artery disease (CAD) have
      traditionally been regarded as two separate vessel disorders with a common
      background. Atherosclerosis has always been considered as the basic
      pathophysiologic process. However, during the last decade, evidence has emerged
      with differences between AAA and CAD. Firstly, data regarding the prevalence of
      AAA and CAD are different. Secondly, the risk profiles between AAA and CAD
      differ, mainly regarding gender, age and diabetes mellitus. Thirdly, despite the
      intensive treatment of CAD and improved outcome, the prevalence of AAA has not
      changed during the last decade. In this review we will discuss the
      characteristics of CAD in patients with AAA. In the first part we focus on
      epidemiological data of CAD in AAA patients. The pathophysiology of both AAA and
      CAD will be described in the second part. There is a common pathway between
      pathophysiology and risk profiles that is discussed in the third chapter. Based
      on the presence of risk factors and their influence on cardiovascular events, the
      preoperative work-up and testing for CAD in AAA has gained an important role. The
      role of (non)-invasive testing will be described in the fourth chapter. The
      treatment of AAA traditionally consisted solely of surgery. However, due to the
      influence of CAD on adverse outcomes, medical intervention is potentially useful.
      Surgical approaches for the treatment of both AAA and CAD, and most importantly,
      their influence on long-term outcome will be discussed in the fifth chapter.

PMID- 19179997
TI  - Endoscopic subureteral injection for vesicoureteral reflux and the risk of
      overtreatment.
AB  - AIM: Risk of vesicoureteral reflux (VUR) overtreatment was anticipated following
      introduction of endoscopic treatment (ET). New tool reduces hospitalization and
      patients discom-fort, with good results and parental preferences may prevail on
      questions about benefits of treatment. The authors analyzed two series of
      patients to evaluate impact of ET on management. METHODS: Two hundred sixty-four
      patients were selected; group A (90 cases) were observed and treated before
      adoption of ET. Group B included 174 patients who benefited of ET (Deflux).
      Treatment started from grade III (infections or renal damage). Lower refluxes
      were treated only in association to an higher grade in the other kidney. 81
      ureters were reinplanted in Group A (92% success rate); 67 ureters were
      reinplanted in group B (98% sr) and 115 had a ET (89% sr). Rate of treatment,
      time of follow up and age at operation were compared. RESULTS: No differences
      were found in order to reflux grade distribution, treatment rate and time spent
      waiting for spontaneous before reinplant or ET. ET was a first choice procedure,
      for grade III, in group B. Reinplant continued to have a role for grade IV cases,
      which responded to ET in 85%, and for grade V. Spontaneous resolution was
      observed respectively in 29% and 30% (grade III) and 13% and 7% (grade IV).
      CONCLUSIONS: Despite ET is accessible and effective, there are no evidences that
      extensive indications are of any benefit. Enthusiasm for new tools must be
      submitted to the need for long term, prospective studies to support our
      indications.

PMID- 19179996
TI  - Prognosis of patients with peripheral arterial disease.
AB  - The incidence of peripheral arterial disease (PAD) is on the increase and is
      associated with a major health concern in current practical care. The most common
      disease process underlying PAD is atherosclerosis. Atherosclerosis is a complex
      generalized disease affecting several arterial beds, including the peripheral and
      coronary circulation. Especially in patients with PAD, high incidences of
      coronary artery disease (CAD) have been observed, which may be asymptomatic or
      symptomatic. The prognosis of patients with PAD is related to the presence and
      extent of underlying CAD. In patients with PAD undergoing major vascular surgery,
      cardiac complications are the major cause of perioperative morbidity and
      mortality and indicate a high-risk for adverse long-term cardiac outcome. In
      order to improve outcome for PAD patients, assessment and aggressive therapy of
      atherosclerotic risk factors and usage of cardio-protective medications is
      recommended. Unfortunately, substantial differences in risk factor management and
      treatment and long-term outcome have been reported between PAD and CAD patients.

PMID- 19179998
TI  - [Assessment of breast feeding rates during compulsory vaccination: preliminary
      outcomes].
AB  - AIM: In consideration of the World Health Organization (WHO) recommendations on
      promoting and supporting breast feeding, a measurement of breast feeding rates
      was planned within Vercelli's Province (ASL 11, Piedmont, Italy) in order to
      compare the local situation to the national and international one, and to promote
      ideas and strategies for increasing the practice of breast feeding up to six
      months or beyond. METHODS: During Diptheria Tetanus whole cell Pertussis
      vaccination (DTP) vaccination a questionnaire about their children's feeding was
      handed out to all mothers. Preliminary outcomes were elaborated after a follow-up
      of six months. RESULTS: So far 1591 questionnaires have been collected. During
      the first DTP immunizations 31.63% of the children were exclusively breastfed and
      15.81% were partially breastfed. At the second vaccination, 11.14% and 37.68% of
      infants were completely and partially breastfed, respectively. A 36.11% of
      partially breast feeding still emerged during the third DTP vaccination.
      CONCLUSIONS: The outcomes of this study are inferior compared to WHO expectation
      and to national statistics. Increasing breast feeding rates should consequently
      become a priority aim, pursuing it through the health workers training, the
      support of mothers who encounter difficulties during their hospital stay or at
      home, and making the public aware of breast feeding practices.

PMID- 19179999
TI  - High prevalence of vitamin D deficiency in young children in a highly sunny humid
      country: a global health problem.
AB  - AIM: Several studies indicate a high prevalence of vitamin D deficiency among
      young populations. Information about the vitamin D status in young adult
      populations from the Middle East is scarce. The vitamin D status can be expected
      to be influenced by highly different factors between various countries in Europe,
      the Middle East and Asia. The aim of this study was to determine the prevalence
      of vitamin D deficiency in young Qatari children below 16 years of age. METHODS:
      A cross-sectional study carried out among children below 16 years of age who
      visited the Primary Health Care Centers (PHCs). The survey was conducted over a
      period from August 2007 to March 2008. Qatari nationals, male and female, aged
      below 16 years. A random sample of 650 children who visited the PHC Centers was
      approached and parents of 458 children expressed their consent to participate in
      this study, corresponding to a response rate of 70.5%. Face-to-face interviews
      were based on a questionnaire that included variables such as socio-demographic
      information, life style, family history and feeding patterns during infancy, and
      clinical information as well as laboratory investigations for biochemical
      assessment of vitamin D status. RESULTS: Of the total number of 458 children
      surveyed, 228 (49.8%) were males and 230 (50.2%) females. The prevalence of
      vitamin D deficiency among the studied Qatari children was (68.8%), mostly in the
      age group (11-16) years (61.6%). There was a significant difference between
      vitamin D deficient and normal children as compared to their age (P=0.013).
      Vitamin D deficiency was more common among girls (51.4%) than boys (48.6%).
      Exposure to sunlight was limited in both groups; but even lower in vitamin D
      deficient children (57.5%) than in normal children (70.6%). The duration of time
      spent outside was again low in both groups but significantly lower in vitamin D
      deficient children (23.5 minutes) compared to normal children (28.4 minutes). Low
      duration of time spent outdoors, breast feeding less than 6 months, a family
      history of diabetes mellitus and physical activity were significant predictors
      for vitamin D deficiency in Qatari children. Rickets, fractures, gastroenteritis
      and delayed milestones were all significantly higher in vitamin D deficient
      children. CONCLUSIONS: The present study revealed that the prevalence of vitamin
      D deficiency is high in Qatari children and more common in Qatari girls. In the
      young population in Qatar, vitamin D deficiency appears to result from a
      combination of limitations in sunlight exposure and a low oral intake of vitamin
      D.

PMID- 19180000
TI  - Management of shock in children in the emergency department.
AB  - Early recognition of shock is the key to successful resuscitation in critically
      ill children. Often, shock results in or co-exists with myo-cardial dysfunction
      or acute lung injury. Recognition and appropriate management of these insults is
      crucial for successful outcomes. Resuscitation should be directed to restoration
      of tissue perfusion and normalization of cardiac and respiratory function. The
      underlying cause of shock should also be addressed urgently. The physiological
      response of individual children to shock resuscitation varies and is often
      variable and unpredictable. Therefore, repeated assessments with continuous, non
      invasive monitoring are needed for taking appropriate decisions in the ED.
      Although global indices of tissue oxygen delivery such as the mixed venous oxygen
      saturation (SvO(2)) help in targeting therapies more accurately, it is often
      unavailable in emergency settings. Isotonic fluids form the cornerstone of
      treatment and the amount required for resuscitation is based on etiologies and
      therapeutic response. After resuscitation has been initiated, targeted history
      and clinical evaluation must be performed to ascertain the cause of shock.
      Management of co-morbidities such as asthma and seizures should be implemented
      simultaneously. Inotropes, respiratory support, antibiotics and steroids may also
      be needed during the management of shock. While the management of shock can be
      protocol based, the treatment needs to be individualized depending on the
      suspected etiology and therapeutic response.

PMID- 19180001
TI  - The management of tracheobronchial obstruction in children.
AB  - Tracheobronchial obstruction is very uncommon in children and small infants.
      Stenosis and malacia, either congenital or acquired, are probably the most
      frequent diagnosis in this setting. Clinical symptoms are common to both airway
      anomalies and bronchoscopy plays a crucial role in the diagnostic work-up.
      Management is complex and surgeons involved in it should be familiar with
      multiple surgical and endoscopical techniques. Symptomatic short tracheal
      stenosis are best treated by means of resection and reconstruction, although
      endoscopic dilation or laser resection can be tried first in selected cases. In
      long tracheal stenosis, slide tracheoplasty is the surgical procedure of choice.
      Tracheobronchial malacia is usually self-limiting by the age of 3 years and most
      cases show mild symptoms that can be treated conservatively. In a small group of
      patients airway compromise is severe enough to require surgical or endoscopical
      treatment. Aortopexy or tracheostomy are the classic treatments for congenital
      tracheomalacia, but increasing experience with endoscopic airway stent placement
      in children is making this technique more attractive and popular. Acquired
      tracheomalacia is usually caused by a long-standing tracheostomy and if
      decannulation is impaired surgical treatment is mandatory.

PMID- 19180002
TI  - Genitourinary emergencies in children.
AB  - The aim of this paper was to to provide the primary care practitioner with a
      review of genitourinary conditions in children requiring emergent urological
      referral. These conditions include the acute scrotum/testicular torsion, scrotal
      masses, penile abnormalities, urinary retention and bladder outlet obstruction,
      abdominal masses, acute urinary stones, urinary trauma, genital abnormalities,
      complex anomalies and acute abdomen in patients with previous continent
      reconstruction. The authors discussed the presenting signs and symptoms, proper
      initial diagnostic work-up and the usual therapeutic course of management after
      evaluation by the pediatric urologist.

PMID- 19180003
TI  - [Pediatric functional gastrointestinal disorders: a questionnaire on pediatric
      gastrointestinal symptoms based on Rome III criteria].
AB  - Functional Gastrointestinal Disorders (FGIDs) are defined as a variable
      combination of chronic or recurrent gastrointestinal symptoms, age dependent, not
      explained by structural or biochemical abnormalities. Recurrent gastrointestinal
      disorders, especially abdominal pain, are one of the most common reasons for
      medical consultation among children and adolescents. A population-based study
      demonstrated that 28-46% of school age children complain of abdominal pain each
      week. Only in 10% of the cases an organic cause can be identified, while most of
      the children and adolescents who present these symptoms have a functional
      disorder without any evidence of disease. FGIDs significantly influence the
      quality of life of affected children and have a big social impact related to
      socialization, school absences and could have long-term psychological
      implications. A complete understanding of the pathophysiology of FGIDs remains
      elusive. FGIDs are a multifactorial condition and diverse pathophysiologic
      mechanisms appear to contribute to them, including altered motility, visceral
      hyperalgesia, brain-gut disturbances, genetic and environmental factors, and
      psychosocial upsets, among others. In 2006 the new version of the Questionnaire
      on Pediatric Gastrointestinal Symptoms (QPGS) based on Rome III Criteria (QPGS
      RIII) was created, in order to validate such criteria and to facilitate the
      diagnosis of FGDIs in children and adolescents. The Italian translation of the
      QPGS-RIII has been realized by our research group to spread a valid and universal
      method to screen the children potentially affected by FGDIs.

PMID- 19180004
TI  - [Primary and secondary prevention procedures of temporo-mandibular joint disease
      in the evolutive age].
AB  - In the last years prevention of temporomandiboular joint (TMJ) disease had
      acquired great importance. According to the neuro-occlusal rehabilitation (RNO)
      it is possible to say that TMJ disease starts since first years of life. So it is
      important both for dentist and for pediatric know what are the conditions and the
      atypical functions which predispose to this pathology. The aim of this work was
      to show how it is possible to intercept since primary teeth and the correct norms
      of primary and secondary prevention.

PMID- 19180005
TI  - [Measurement of exhaled nitric oxide].

PMID- 19180006
TI  - [Hospital assistance of children with chronic diseases].

PMID- 19180007
TI  - [A rare case of esophageal atresia type I].
AB  - An extremely rare case of type A esophageal atresia is reported. The baby girl
      patient born spontaneously after a 38-week pregnancy, was diagnosed prenatally
      with suspected type A esophageal atresia. Diagnosis was confirmed at birth by
      chest and abdominal X-ray. As per protocol, a naso-esophageal tube was positioned
      in aspiration and a Stamm gastrostomy made for nutritional purposes. Evaluation
      of the distance between blind pouches at one month of life showed they were
      overlapping. At intervention the pouches were found to be united by a fibrous
      bridge about 1.5 cm long. Anastomosis was carried out with ease. The
      postoperative course was trouble-free. On the X day the baby girl was being fed
      completely per os. Histolo-gical examination of the fibrous residue excluded the
      presence of a mucosa-lined lumen. X-ray examination of the esophageal-gastric
      passage, one month after the operation, showed the smooth transit of the contrast
      medium and an adequate anastomotic lumen. At follow-up, at the age of 9 months,
      the baby was growing normally and being fed per os with a diet appropriate for
      her age; no oesophageal dilatation was necessary. Type A oesophageal atresias are
      long-gap forms: they are treated with direct anastomosis after the blind pouches
      come together spontaneously in the first four months of life. Stress is laid on
      the rarity of the case. According to Kluth's classification of 1976, this form
      was described by Mason in 1855 and Jlott in 1905 on the basis of autopsy
      findings. A review of the literature did not show any similar clinical cases.

PMID- 19180008
TI  - Atypical Epstein-Barr-Virus infection in a 5-year-old girl.
AB  - Primary Epstein-Barr virus (EBV) infection is often asymptomatic before five
      years of age, whereas it is more likely to be symptomatic in older children,
      adolescents and young adults. The classic triad of symptoms including fever,
      pharyngitis and lymphadenopathy is well known, but the spectrum of clinical
      manifestations associated with EBV infection is large and continues to expand,
      including increasing atypical presentations. This article presents the case of a
      five-year-old female in which only a protracted and severe itch, resistant to
      antihistamines, caught the attention of the girl's parents, thus allowing the
      diagnosis of EBV. Furthermore, EBV related splenomegaly and mild hepatitis as
      well as thrombocytopenia had an atypical prolonged course.

PMID- 19180009
TI  - Primary Sjogren's syndrome mimicking lymphoma in a pediatric patient. A rare and
      possibly misdiagnosed condition.
AB  - A 12-year-old girl presented at the Oncoemato-logic Department with an acute
      onset of generalized lymphadenopathy. Lymphoproliferative disorders were highly
      suspected. Biopsied cervical and inguinal lymph node disclosed neither malignant
      cells nor monoclonal proliferation of lymphocytes. Revaluating the diagnosis,
      anamnestic data revealed multiple episodes of bilateral parotid swelling since
      age one, without systemic symptoms. Laboratory investigations, parotid ecography,
      Schirmer test revealed Sjogren's syndrome without associated disease. Sjogren
      syndrome (SS) in childhood is a rare and possibly underdiagnosed condition.

PMID- 19180010
TI  - [Syringocele in children: an unusual presentation as scrotal mass].
AB  - Syringocele is a cystic dilation of the excretory bulbourethral Cowper gland
      duct, and is a rather uncommon finding in pediatric age. It is frequently
      asymptomatic but sometimes may cause voiding symptoms and urinary tract infection
      (UTI). This case report describes an unusual manifestation of syringocele
      presenting with hydrocele. The case concerns a 2-year-old boy who was referred to
      our Clinic with a diagnosis of hydrocele. The patient underwent hydrocelectomy
      through a bilateral inguinal incision, but no clear communication with the patent
      peritoneal vaginal ducts could be demonstrated. The histology evidenced an
      epidermoid cyst. One year later the scrotal mass relapsed. Sonography, voiding
      cistography (VCG), computed tomography (CT) scan and magnetic resonance imaging
      (MRI) were performed. VCG, CT scan and MRI demonstrated the communication between
      the urethra and the scrotal mass. A surgical excision of the syringocele with
      endoscopic resection of the collar were performed. Syringocele is a rare entity
      in pediatrics. To this authors' knowledge there are no reports in the literature
      describing cases presenting with scrotal mass.

PMID- 19180061
TI  - Predictors of first-fill adherence for patients with hypertension.
AB  - BACKGROUND: Between the promise of evidence-based medicine and the reality of
      inadequate patient outcomes lies patient adherence. Studies of prescription
      adherence have been hampered by methodologic problems. Most rely on patient self
      report of adherence or cross-sectional data of plan-wide prescription fills to
      estimate patient-level adherence. METHODS: We conducted a retrospective cohort
      study and linked individual patient data for incident prescriptions for
      antihypertensive medications from electronic health records (EHRs) to claims data
      obtained from the patient's insurance plan. Clinical data were obtained from the
      Geisinger Clinic, a 41 site group practice serving central and northeastern
      Pennsylvania with an EHR in use since 2001. Adherence was defined as a
      prescription claim generated for the first-fill prescription within 30 days of
      the prescribing date. RESULTS: Of the 3,240 patients written a new, first-time
      prescription for an antihypertensive medication, 2,685 (83%) generated a
      corresponding claim within 30 days. Sex, age, therapeutic class, number of other
      medications prescribed within 10 days of the antihypertensive prescription,
      number of refills, co-pay, comorbidity score, baseline blood pressure (BP), and
      change in BP were significantly associated with first-fill rates (P < 0.05).
      CONCLUSIONS: Patients who are older, female, have multiple comorbidities, and/or
      have relatively lower BPs may be less likely to fill a first prescription for
      antihypertensive medications and may be potential candidates for interventions to
      improve adherence to first-fill prescriptions.

PMID- 19180062
TI  - Nexfin noninvasive continuous blood pressure validated against Riva
      Rocci/Korotkoff.
AB  - BACKGROUND: The Finapres methodology offers continuous measurement of blood
      pressure (BP) in a noninvasive manner. The latest development using this
      methodology is the Nexfin monitor. The present study evaluated the accuracy of
      Nexfin noninvasive arterial pressure (NAP) compared with auscultatory BP
      measurements (Riva-Rocci/Korotkoff, RRK). METHODS: In supine subjects NAP was
      compared to RRK, performed by two observers using an electronic stethoscope with
      double earpieces. Per subject, three NAP-RRK differences were determined for
      systolic and diastolic BP, and bias and precision of differences were expressed
      as median (25th, 75th percentiles). Within-subject precision was defined as the
      (25th, 75th percentiles) after removing the average individual difference.
      RESULTS: A total of 312 data sets of NAP and RRK for systolic and diastolic BP
      from 104 subjects (aged 18-95 years, 54 males) were compared. RRK systolic BP was
      129 (115, 150), and diastolic BP was 80 (72, 89), NAP-RRK differences were 5.4 (
      1.7, 11.0) mm Hg and -2.5 (-7.6, 2.3) mm Hg for systolic and diastolic BP,
      respectively; within-subject precisions were (-2.2, 2.3) and (-1.6, 1.5) mm Hg,
      respectively. CONCLUSION: Nexfin provides accurate measurement of BP with good
      within-subject precision when compared to RRK.

PMID- 19180063
TI  - Evaluation of systolic properties in hypertensive patients with different degrees
      of diastolic dysfunction and normal ejection fraction.
AB  - BACKGROUND: Left ventricular (LV) diastolic dysfunction (DD) associated with a
      preserved ejection fraction (EF) is a frequent alteration in hypertensive
      patients, usually considered an impairment of the diastolic phase alone. However,
      because systole and diastole are strictly correlated to one another, it is
      possible that hypertensive patients with isolated DD may also present with
      initial abnormalities of LV systolic properties, particularly those presenting
      with a more severe degree of DD. We performed a multiparametric echocardiographic
      assessment of LV systolic properties in patients without cardiovascular diseases,
      with preserved EF and different degrees of DD. METHODS: We evaluated 1,073
      hypertensive subjects showing EF >55% and no overt heart disease. RESULTS: A
      total of 362 patients had normal diastolic function (N), 609 displayed delayed
      relaxation pattern (DR), and 102 presented a pseudonormal filling pattern (PN).
      Albeit most of the subjects with DD (DR, PN) had systolic indexes within normal
      range, they presented a significant reduction of index stroke volume (SV) (P <
      0.0001) and stroke work (SW) (P < 0.0001), EF (P < 0.01), midwall shortening
      (MFS) (P < 0.0001), circumferential end-systolic stress-corrected MFS (cESS-MFS)
      (P < 0.001), and tissue Doppler (TD) systolic velocity (P < 0.0001) as compared
      to the N group, particularly the PN group.After adjustments, the reductions of LV
      systolic indexes were still significantly related to DD, particularly to PN.
      CONCLUSIONS: Our results suggest a relation between LV systolic and diastolic
      properties in patients with normal EF. They also highlight the early onset of a
      preclinical reduction of systolic properties in patients with "isolated" DD,
      which is related to the degree of dysfunction.

PMID- 19180064
TI  - Reductions in internal disinhibition during weight loss predict better weight
      loss maintenance.
AB  - The construct of disinhibition, as measured by the Eating Inventory, was recently
      found to have two factors: internal disinhibition (eating in response to
      cognitive and emotional cues) and external disinhibition (eating in response to
      environmental cues). This study examined whether early changes in disinhibition
      that occurred during a weight loss program predicted later weight loss
      maintenance. Participants were adults enrolled in a weight loss treatment study
      (n = 81, 16% men, BMI = 38.4 +/- 6.5 kg/m(2)). Two-thirds of participants were
      African Americans. Participants received a uniform, meal-replacement-based weight
      loss program in months 1-3 and one of four nutritionally focused programs for
      weight loss maintenance in months 4-12. Disinhibition and weight were assessed at
      clinic visits. Change in internal disinhibition from months 1-3 (i.e., the weight
      loss period) significantly predicted change in weight from month 4 to 12 (i.e.,
      the weight maintenance period); this remained significant when treatment group,
      age, gender, ethnicity, baseline weight, baseline depression, baseline internal
      disinhibition, and initial weight loss were controlled for (P = 0.03). A
      comparable analysis examining change in external disinhibition found that it was
      not a significant predictor of weight maintenance (P = 0.43). Participants who
      experienced the biggest decreases in internal disinhibition during the initial
      phase of treatment had the most success maintaining their weight loss in the next
      phase of treatment. Long-term weight loss outcomes may be improved by spending
      sufficient treatment time teaching strategies for reducing eating in response to
      internal cues.

PMID- 19180065
TI  - Prevention of weight gain in adult patients with type 2 diabetes treated with
      pioglitazone.
AB  - Pioglitazone, a thiazolidinedione (TZD) commonly used to treat type 2 diabetes,
      is associated with weight gain. Our study was designed to examine the
      effectiveness of three lifestyle-treatment programs of varying intensity on
      prevention of pioglitazone-induced weight gain and to measure the composition of
      the change in body weight. Thirty-nine adult overweight and obese subjects with
      type 2 diabetes mellitus were all treated with pioglitazone and prospectively
      randomized to one of three lifestyle-treatment programs with increasing level of
      intensity for 24 weeks. Body composition was measured by dual-energy X-ray
      absorptiometry (DXA), computed tomography, and multifrequency bioimpedance
      analysis both before and after therapy. Subjects demonstrated a "dose-response"
      effectiveness to three levels of lifestyle intervention to mitigate pioglitazone
      induced weight gain. Mean (s.d.) weight change (kg) for the usual, standard, and
      intensive lifestyle groups were 4.9 +/- 4.9 (P = 0.005), 1.8 +/- 3.4 (P = 0.02),
      and -0.2 +/- 4.4 (NS) respectively. Total body fat increased 2.6 +/- 3.4 kg (P =
      0.04) for the usual group and decreased for the intensive group -0.4 +/- 3.5
      (NS). Change in abdominal subcutaneous and visceral adipose tissue (VAT) did not
      differ between groups, although ratio of visceral/subcutaneous fat decreased for
      the standard and intensive groups (NS). Both usual (P < 0.05) and standard care
      (NS) groups gained total body water. This is the first prospective, randomized
      study that demonstrates the beneficial effect of participation in a comprehensive
      lifestyle-weight-management program on lessening of weight gain associated with
      pioglitazone.

PMID- 19180066
TI  - Vitamin D in overweight/obese women and its relationship with dietetic and
      anthropometric variables.
AB  - Overweight/obese persons usually have an inadequate vitamin D status, a situation
      commonly made worse by an inadequate intake of this vitamin. For this reason, the
      aim of this study was to analyze dietetic and anthropometric differences in a
      group of young, overweight/obese Spanish women with respect to their vitamin D
      status. The study subjects were 66 white Spanish women (aged 20-35 years) with a
      BMI of 24-35 kg/m(2). Dietetic, anthropometric, and biochemical data were
      collected. Women were divided into two groups depending on their serum vitamin D
      concentrations: LD (women with <90 nmol/l 25(OH)D) and HD (women with >or=90
      nmol/l 25(OH)D). The intakes of vitamin D, calcium, and supplements were similar
      in both groups. The body weight, BMI, and waist circumference of the HD subjects
      were smaller than those recorded for the LD subjects (68.6 +/- 4.2 kg, 26.0 +/-
      1.3 kg/m(2), and 79.4 +/- 3.4 cm compared to 76.2 +/- 9.8, 28.6 +/- 3.2 kg/m(2),
      and 86.2 +/- 9.3 cm, respectively; P < 0.05). The hip circumference and the
      waist/hip ratio were similar in both groups. A BMI of <27.7 kg/m(2) (P50) was
      associated with serum vitamin D concentrations of >or=90 nmol/l (odds ratio =
      0.1313; confidence interval: 0.0149-1.1599; P < 0.05). Overweight/obese women are
      at higher risk of vitamin D deficiency, largely due to excess adiposity rather
      than inadequate intake.

PMID- 19180067
TI  - The association between sleep duration and general and abdominal obesity in
      Koreans: data from the Korean National Health and Nutrition Examination Survey,
      2001 and 2005.
AB  - This study aimed to investigate the association between self-reported sleep
      duration and general and abdominal obesity in Korean adults. A total of 8,717
      adults aged 20-65 years from the Korean National Health and Nutrition Examination
      Survey (KNHANES) 2001 and 2005 were included. General obesity was defined as BMI
      >or=25 kg/m(2) and abdominal obesity as waist circumference >or=90 cm in men and
      >or=85 cm in women. To control for sociodemographic and lifestyle factors and
      comorbidities, multivariable logistic regression was used to calculate the
      adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of general and
      abdominal obesity across the following sleep duration categories: <or=5, 6, 7, 8,
      and >or=9 h/day. Mean sleep duration (+/-s.d.) was 6.9 +/- 1.3 h. Those sleeping
      <or=5 h/day had the highest BMI and waist circumference compared with those
      sleeping 7, 8, or >or=9 h/day (P < 0.05 for all comparisons). After controlling
      for sociodemographic and lifestyle factors, the adjusted ORs (95% CIs) associated
      with sleeping <or=5 h/day (vs. 7 h/day) were 1.25 (1.06-1.48) for general obesity
      and 1.24 (1.03-1.48) for abdominal obesity. Further adjustment for hypertension
      and diabetes mellitus did not significantly affect the associations. These data
      suggest that short sleep duration is significantly associated with a modest
      increase in general and abdominal obesity in Korean adults.

PMID- 19180069
TI  - Obesity and menstrual irregularity: associations with SHBG, testosterone, and
      insulin.
AB  - This cross-sectional study aimed to examine the association between different
      body composition measures, menstrual cycle characteristics, and hormonal factors
      in a population-based sample of young women. The study sample included 726
      Australian women aged 26-36 years who were not currently taking hormonal
      contraceptives and were not currently pregnant or breast feeding. Anthropometric
      measures included BMI, waist circumference (WC), and waist-hip ratio (WHR).
      Menstrual cycle characteristics were self-reported and usual cycles defined as
      short (<or=25 days), normal (26-34 days), or long (>or=35 days). Cycles were
      defined as irregular if there were >or=15 days between the longest and shortest
      cycle in the past 12 months. Fasting serum levels of sex hormone-binding globulin
      (SHBG), testosterone, insulin, and glucose were measured and the free androgen
      index (FAI) derived. Compared with those of normal weight, obese women had at
      least a twofold greater odds of having an irregular cycle, whether defined by BMI
      (odds ratio (OR) = 2.61; 95% CI = 1.28-5.35), WC (OR 2.28; 95% CI = 1.16-4.49),
      or WHR (OR = 2.27; 95% CI = 1.09-4.72). Body composition measures were
      significantly positively associated with fasting insulin, testosterone, and FAI,
      and negatively associated with SHBG (P < 0.01). Fasting insulin, SHBG, and FAI
      had the strongest influence on the associations between obesity and irregular
      cycles, with statistically significant ORs of having an irregular cycle being
      attenuated to near null values following adjustment. In conclusion, both overall
      and central obesity were significantly associated with having an irregular
      menstrual cycle. This association was substantially influenced by hormonal
      factors, particularly insulin and SHBG.

PMID- 19180068
TI  - A statewide intervention reduces BMI in adults: Shape Up Rhode Island results.
AB  - Given the epidemic of obesity, approaches to weight loss that can be applied on a
      community, state, or national level are needed. We report results from Shape Up
      Rhode Island 2007 (SURI), a statewide Internet-based program involving team-based
      competition to increase physical activity and achieve weight loss. A total of
      4,717 adults (84% women; mean BMI = 29.6 kg/m(2)) enrolled in the 16-week weight
      loss competition of SURI and 3,311 completed at least 12 weeks. Completers
      reported losing 3.2 +/- 3.4 kg, and 30% achieved a clinically significant weight
      loss of >or=5%. Although modest, these weight losses shifted the BMI distribution
      from a mean BMI of 29.4 to a mean of 28.2 kg/m(2) and reduced the population that
      was obese from 39 to 31%. More conservative intent-to-treat analyses and analysis
      of 132 participants with objective weights still showed a significant reduction
      in BMI of -0.8 units. These findings suggest that statewide weight loss campaigns
      can produce modest weight losses in large numbers of participants. These data
      provide a benchmark that can be used for comparisons with other statewide
      campaigns. Research on ways to improve such campaigns is needed.

PMID- 19180070
TI  - Truncal and abdominal fat as determinants of high triglycerides and low HDL
      cholesterol in adolescents.
AB  - We examined whether abdominal and truncal adiposity, assessed with simple
      anthropometric indices, determines serum triglycerides and high-density
      lipoprotein (HDL)-cholesterol levels independently of total adiposity amount in
      adolescents. A total of 547 Spanish adolescents (284 males and 263 females) aged
      13-18.5 years were included in this study. Measures of truncal adiposity included
      subscapular to triceps ratio, and trunk-to-total skinfolds ratio (TTS%). Waist
      circumference was used as a surrogate of abdominal adiposity, and BMI was used as
      a measure of total adiposity. The results of the regression models indicated that
      levels of triglycerides were positively associated with waist circumference and
      TTS% after controlling for age and Tanner stage in both sexes. Once BMI was
      entered in the model, these associations remained significant for waist
      circumference in females. HDL-cholesterol levels were negatively associated with
      waist circumference in both sexes, and with subscapular to triceps ratio and TTS%
      in males, after controlling for age and Tanner stage. Once BMI was entered in the
      model, these associations remained significant for subscapular to triceps ratio
      and for TTS% in males. The results of this study suggest that in male
      adolescents, truncal adiposity is negatively associated with levels of HDL
      cholesterol, whereas in females, abdominal adiposity is positively associated
      with levels of triglycerides independently of total adiposity. These findings
      highlight the deleterious effect of both truncal and abdominal fat depots on the
      lipid profile already from the first decades of life.

PMID- 19180072
TI  - The common variant in the FTO gene did not modify the effect of lifestyle changes
      on body weight: the Finnish Diabetes Prevention Study.
AB  - The common single-nucleotide polymorphism in the FTO (fat mass and obesity
      associated) gene is consistently associated with an increased risk of obesity.
      However, the knowledge of a potential modifying effect of the FTO gene on changes
      in body weight achieved by lifestyle intervention is limited. We examined whether
      the FTO gene variant (rs9939609, T/A) is associated with body weight and BMI and
      long-term weight changes in the Finnish Diabetes Prevention Study (DPS).
      Altogether, 522 (aged 40-65 years; BMI >or=25 kg/m(2)) subjects with impaired
      glucose tolerance (IGT) were randomized to control and lifestyle intervention
      groups. SNP rs9939609 was genotyped from 502 subjects. At baseline, those with
      the AA genotype had higher BMI than subjects with other genotypes (P = 0.006).
      The association was observed in women (P = 0.016) but not in men. During the 4
      year follow-up, the subjects with the AA genotype had consistently the highest
      BMI (P = 0.009) in the entire study population. The magnitude of weight reduction
      was greater in the intervention group, but the risk allele did not modify weight
      change in either of the groups. Our results confirm the association between the
      common FTO variant and BMI in a cross-sectional setting and during the long-term
      lifestyle intervention. We did not observe association between FTO variant and
      the magnitude of weight reduction achieved by long-term lifestyle intervention.
      Based on the results from the DPS, it is unlikely that the common variant of the
      FTO gene affects the success of lifestyle modification on weight loss.

PMID- 19180073
TI  - A sensitive recombinant cell-based bioluminescent assay for detection of androgen
      like compounds.
AB  - We report a step-by-step protocol describing how to develop and use a yeast-based
      bioassay for androgen-like compounds. Saccharomyces cerevisiae cells are
      genetically engineered to express the human androgen receptor (hAR) and the
      bioluminescent (BL) reporter gene luciferase (from Photinus pyralis) under the
      control of the androgen response element (ARE). In the presence of androgens,
      activated hAR binds to the ARE sequences and activates luciferase expression.
      After addition of D-luciferin, luciferase activity measurements can be performed,
      and the BL signal is proportional to the androgenic activity of the sample.
      Cytotoxic effects of the sample are monitored by the use of a control yeast
      strain that allows BL signal correction according to cell viability. After
      overnight culture of the recombinant strain, the assay can be accomplished in a
      96-well microplate format in 1 working day with a detection limit of 0.05 nM for
      testosterone and intra- and interassay variability of 14% and 23%, respectively.

PMID- 19180074
TI  - Methylation-sensitive high-resolution melting.
AB  - The base composition of PCR products derived from sodium bisulfite-modified
      templates is methylation dependent. Hence, methylated and unmethylated, PCR
      products show different melting profiles when subjected to thermal denaturation.
      The methylation-sensitive high-resolution melting (MS-HRM) protocol is based on
      the comparison of the melting profiles of PCR products from unknown samples with
      profiles specific for PCR products derived from methylated and unmethylated
      control DNAs. The protocol consists of PCR amplification of bisulfite-modified
      DNA with primers designed to proportionally amplify both methylated and
      unmethylated templates and subsequent high-resolution melting analysis of the PCR
      product. The MS-HRM protocol allows in-tube determination of the methylation
      status of the locus of interest following sodium bisulfite modification of
      template DNA in less than 3 h. Here, we provide a protocol for MS-HRM, which
      enables highly sensitive, labor- and cost-efficient single-locus methylation
      studies on the basis of DNA high-resolution melting technology.

PMID- 19180075
TI  - In vitro growth and analysis of Candida biofilms.
AB  - Evaluation of fungal biofilm formation can be performed using several techniques.
      In this protocol, we describe methods used to form Candida biofilms on three
      different medical device substrates (denture strips, catheter disks and contact
      lenses) to quantify them and to evaluate their architecture and drug
      susceptibility. Biofilm formation involves adhesion of fungal cells to pretreated
      substrates, followed by growth in medium. Formed biofilms are quantified by
      determining their metabolic activity and dry weight, whereas their gross
      morphology and architecture are evaluated using fluorescence microscopy, scanning
      electron microscopy and confocal scanning laser microscopy techniques.
      Susceptibility of biofilms is determined by comparing their metabolic activity in
      the presence of antifungal agents with that in their absence. The methods
      described here can be completed in a typical laboratory with minimum involvement
      of software. Evaluation of the growth of fungal biofilms and their analyses can
      be completed using the described methods in approximately 15 d.

PMID- 19180076
TI  - A C. elegans-based, whole animal, in vivo screen for the identification of
      antifungal compounds.
AB  - Traditional antimicrobial screens focus on compounds that block the growth of
      microbial organisms. A new Caenorhabditis elegans-based bioassay can be used for
      the identification of antifungal compounds that are effective against Candida
      albicans. According to the protocol, adult nematodes are infected with C.
      albicans and moved to 96-well plates containing the tested compounds. In the
      presence of compounds with no antifungal activity, the fungus kills the worms and
      develops filaments that penetrate through the cuticle. In contrast to traditional
      screening methods and mammalian models, this facile, time-efficient and less
      costly assay allows the study of Candida cells in nonplanktonic form and may
      allow the concurrent evaluation of toxicity and antifungal activity and identify
      compounds that target virulence factors or modify host immune response. The
      screening assay takes about 5-6 d depending on the experimental design.

PMID- 19180077
TI  - In vivo evaluation of human hematopoiesis through xenotransplantation of purified
      hematopoietic stem cells from umbilical cord blood.
AB  - Establishment of robust xenograft models is critical to studying human
      hematopoiesis in a physiologic setting. Using a recently developed
      immunodeficient mouse strain, we have established long-term multilineage human
      grafts and demonstrated their serially transplantability using limited numbers of
      purified human hematopoietic stem cells (HSCs). Herein, we describe our protocol
      for the isolation of human HSC (Lin-CD34+CD38-CD90+) from umbilical cord blood
      (CB) as well as the xenotransplantation system that allows stable engraftment of
      human hematopoietic cells with as few as ten HSCs. Isolation of CB mononuclear
      cells requires 2-3 h, and cells may be cryopreserved before transplantation.
      Isolation of HSC requires approximately 2-3 h, and transplantation requires 1 h.
      Short-term and long-term engraftment is assessed 4-6 weeks and 10-12 weeks post
      transplantation, respectively, with preparation and analysis time requiring 4-8 h
      at each time point.

PMID- 19180078
TI  - SPIDER image processing for single-particle reconstruction of biological
      macromolecules from electron micrographs.
AB  - This protocol describes the reconstruction of biological molecules from the
      electron micrographs of single particles. Computation here is performed using the
      image-processing software SPIDER and can be managed using a graphical user
      interface, termed the SPIDER Reconstruction Engine. Two approaches are described
      to obtain an initial reconstruction: random-conical tilt and common lines. Once
      an existing model is available, reference-based alignment can be used, a
      procedure that can be iterated. Also described is supervised classification, a
      method to look for homogeneous subsets when multiple known conformations of the
      molecule may coexist.

PMID- 19180079
TI  - Expression cloning and radiotracer uptakes in Xenopus laevis oocytes.
AB  - This protocol describes the method of expression cloning of heterologous proteins
      using Xenopus laevis oocytes and the functional characterization of membrane
      proteins using radiotracer assays. It can be used to isolate proteins for which
      sequence data is unavailable and to characterize the functions of proteins. A
      cDNA library is generated, that is, translated into proteins in Xenopus oocytes,
      and the function of these proteins is assessed by a radiotracer assay. Their
      large size, high degree of expression and ease of handling makes Xenopus oocytes
      an optimal tool for the expression and characterization of protein function when
      compared with traditional expression systems, such as Escherichia coli, yeast or
      eukaryotic cell lines. The expected results of this technique include the
      following: functional identification of novel proteins; molecular (kinetic)
      characterization of protein function; and determination of functionally relevant
      residues and domains of membrane proteins, including transporters, ion channels
      and receptors. The identification of novel proteins can take several months,
      whereas functional characterization in Xenopus oocytes can take 1 week.

PMID- 19180080
TI  - Cryopreservation and banking of mammalian cell lines.
AB  - This protocol describes the principles and methods used for the preparation of
      cryopreserved cell stocks. Following these procedures will ensure the
      availability of reproducible cultures for use within a single laboratory at
      different times and for different collaborating laboratories. Although the basic
      principle is simple, each cell line has characteristics that must to be borne in
      mind when establishing and testing such stocks. The key requirements are reliable
      methods for culture, cryopreservation, characterization and quality control.

PMID- 19180081
TI  - Dual fluorescence labeling of surface-exposed and internal proteins in
      erythrocytes infected with the malaria parasite Plasmodium falciparum.
AB  - There is a need for improved methods for in situ localization of surface proteins
      on Plasmodium falciparum-infected erythrocytes to help understand how these
      antigens are trafficked to, and positioned within, the host cell membrane. This
      protocol for confocal immunofluorescence microscopy combines surface antigen
      labeling on live cells with subsequent fixation and permeabilization, which
      enables antibodies to penetrate the cell and label internal antigens. The key
      steps of the protocol are as follows: indirect labeling of the surface antigen
      using a fluorescently tagged secondary antibody; fixation and permeabilization;
      indirect labeling of the internal antigen using a secondary antibody tagged with
      a spectrally distinct fluorescent dye; and detection of the differentially
      labeled antigens using a laser scanning confocal microscope. The protocol can be
      completed in approximately 7 h. Although the protocol is discussed here in the
      context of malaria parasite-infected cells, it can also be modified to visualize
      the membrane and intracellular distribution of surface and internal proteins in
      other eukaryotic cells.

PMID- 19180082
TI  - A protocol for studying the kinetics of RNA within cultured cells: application to
      ribosomal RNA.
AB  - This protocol describes a nonisotopic method for high-resolution investigation of
      the kinetics of RNA within the cell. This involves the incorporation of
      bromouridine-5'-triphosphate into RNA of living cells by lipofection followed by
      immunocytological detection of BrRNAs. The use of the same antibody identified
      either with fluorescence or with gold particles revealed the three-dimensional
      organization of sites containing labeled RNAs or their precise localization by
      using confocal and ultrastructural microscopy, respectively. Comparison of three
      dimensional reconstruction obtained from the series of optical sections and
      ultrathin sections was extremely fruitful to describe topological and spatial
      dynamics of RNAs from their synthesis site inside the nucleus to the cytoplasm.
      Combined with immunolocalization of proteins involved in different nuclear
      activities and with highly resolved three-dimensional visualizations of the
      labelings, this method should also provide a significant contribution to our
      understanding of the functional, volumic organization of the cell nucleus. The
      entire protocol can be completed in approximately 10 d.

PMID- 19180083
TI  - Modeling Pseudomonas aeruginosa pathogenesis in plant hosts.
AB  - A pathogenic model in which both the pathogen and its host are amenable to
      genetic manipulation can greatly facilitate the understanding of bacterial
      pathogenesis. Plants are genetically tractable and can be used as experimental
      models for human microbial pathogenesis. We present protocols for both lettuce
      and Arabidopsis leaf infection models using the opportunistic human bacterial
      pathogen, Pseudomonas aeruginosa. The lettuce model allows for high-throughput
      qualitative analysis of virulence and is suitable for screening large numbers of
      bacterial strains, whereas the Arabidopsis model provides a quantitative approach
      and permits the tracking of bacterial cell proliferation in planta. The lettuce
      model takes approximately 24 h including bacterial growth using store-bought
      lettuce, and the Arabidopsis model takes 4-6 weeks to grow the plants and a
      similar time as with lettuce to infect the plants. Both models are monitored for
      up to 5 d post-infection. These methodologies can and have been used to identify
      novel and critical P. aeruginosa pathogenicity agents, as virulence factors are
      often conserved across phylogeny.

PMID- 19180084
TI  - Protocol for the quantitative assessment of DNA concentration and damage
      (fragmentation and nicks).
AB  - An ultrasensitive protocol is presented for the quantitative assessment of
      fragmented and nicked dsDNA using PicoGreen and consists of four methods. The
      first quantifies the concentration of DNA, whereas the second (quantitative
      complement of the Comet assay) quantifies the degree of DNA fragmentation seen in
      a typical DNA agarose electrophoresis gel. Both methods have sensitivity of 5 pg
      of DNA. The third method (quantitative counterpart of the electrophoresis-based
      qualitative apoptotic and necrotic DNA assays) quantifies the polyethylene glycol
      fractionated small-size (0-1 kb) fragmented DNA. This method also detects up to 5
      pg of damaged DNA and requires a minimum sample of quantity 0.2 ml of 2.5 microg
      ml(-1). The fourth method measures the percentage of DNA nicks by alkaline DNA
      unwinding and requires up to 15 pg of DNA sample. The time required for
      processing 10 DNA samples is 1/2, 1, 13 and 1 h for the first, second, third and
      fourth method, respectively.

PMID- 19180071
TI  - One-year weight losses in the Look AHEAD study: factors associated with success.
AB  - This report provides a further analysis of the first year weight losses in the
      Look AHEAD (Action for Health in Diabetes) study and identifies factors
      associated with success. Participants were a total of 5,145 men and women with
      type 2 diabetes who were recruited at 16 sites and randomly assigned to an
      intensive lifestyle intervention (ILI) or a control condition, Diabetes Support
      and Education (DSE). During year 1, participants in ILI received comprehensive
      diet and physical activity counseling in a total of 42 group and individual
      sessions, compared with three educational sessions for DSE participants. As
      reported previously, at the end of the year, ILI participants lost 8.6% of
      initial weight, compared to 0.7% for DSE (P < 0.001). Within the ILI group, all
      racial/ethnic groups achieved clinically significant weight losses (>5.5%),
      although there were significant differences among groups. For the year, ILI
      participants attended an average of 35.4 treatment sessions and reported
      exercising a mean of 136.6 min/week and consuming a total of 360.9 meal
      replacement products. Greater self-reported physical activity was the strongest
      correlate of weight loss, followed by treatment attendance and consumption of
      meal replacements. The use of orlistat, during the second half of the year,
      increased weight loss only marginally in those ILI participants who had lost <5%
      of initial weight during the first 6 months and chose to take the medication
      thereafter as a toolbox option. The lifestyle intervention was clinically
      effective in all subsets of an ethnically and demographically diverse population.

PMID- 19180085
TI  - Combinatorial libraries of peptide dendrimers: design, synthesis, on-bead high
      throughput screening, bead decoding and characterization.
AB  - Dendrimers are branched synthetic macromolecules. This protocol describes the
      synthesis (1-2 weeks), functional screening (1.5 d) and decoding (2 d) of 'one
      bead-one-compound' combinatorial libraries of dendrimers assembled from amino
      acid building blocks by 'split-and-mix' solid phase peptide synthesis. The method
      resembles that for synthesizing linear peptides, except that a branching diamino
      acid is used at every third position to obtain the dendritic structure.
      Structural diversification by splitting is restricted to four amino acids per
      variable position, yielding libraries of approximately 60,000 sequences. In such
      libraries, the sequence of a dendrimer can be deduced uniquely from an amino-acid
      analysis of the solid support bead. This analysis is more reliable, faster and
      far less costly than Edman sequencing such that decoding multiple beads is
      affordable. The method is exemplified for the identification of catalytic peptide
      dendrimers catalyzing the hydrolysis of acyloxypyrene-trisulfonates with
      substrate binding (K(M) = 10-300 microM) and rate accelerations up to
      k(cat)/k(uncat) = 10(4) in aqueous buffer.

PMID- 19180086
TI  - Isolation and cultivation of stem cells from adult mouse testes.
AB  - The successful isolation and cultivation of spermatogonial stem cells (SSCs) as
      well as induction of SSCs into pluripotent stem cells will allow us to study
      their biological characteristics and their applications in therapeutic
      approaches. Here we provide step-by-step procedures on the basis of previous work
      in our laboratory for: the isolation of testicular cells from adolescent mice by
      a modified enzymatic procedure; the enrichment of undifferentiated spermatogonia
      by laminin selection or genetic selection using Stra8-EGFP (enhanced green
      fluorescent protein) transgenic mice; the cultivation and conversion of
      undifferentiated spermatogonia into embryonic stem-like cells, so-called
      multipotent adult germline stem cells (maGSCs); and characterization of these
      cells. Normally, it will take about 16 weeks to obtain stable maGSC lines
      starting from the isolation of testicular cells.

PMID- 19180087
TI  - Electrical stimulation systems for cardiac tissue engineering.
AB  - We describe a protocol for tissue engineering of synchronously contractile
      cardiac constructs by culturing cardiac cells with the application of pulsatile
      electrical fields designed to mimic those present in the native heart. Tissue
      culture is conducted in a customized chamber built to allow for cultivation of
      (i) engineered three-dimensional (3D) cardiac tissue constructs, (ii) cell
      monolayers on flat substrates or (iii) cells on patterned substrates. This also
      allows for analysis of the individual and interactive effects of pulsatile
      electrical field stimulation and substrate topography on cell differentiation and
      assembly. The protocol is designed to allow for delivery of predictable
      electrical field stimuli to cells, monitoring environmental parameters, and
      assessment of cell and tissue responses. The duration of the protocol is 5 d for
      two-dimensional cultures and 10 d for 3D cultures.

PMID- 19180089
TI  - The preparation and development of cellular membrane affinity chromatography
      columns.
AB  - Cellular membrane affinity chromatography is a technique that is based on the
      immobilization of a target trans-membrane protein onto a stationary phase. The
      target protein is isolated by homogenization and solubilization of a source
      (e.g., cell line) followed by immobilization on either the immobilized artificial
      membrane-phosphatidyl choline (IAM-PC) stationary phase or the surface of an open
      tubular capillary during a dialysis step. The procedure typically takes 3-4 d for
      the IAM-PC stationary phase, whereas the open-tubular method takes an extra week
      for the preparation of the capillary. The resulting columns can then be used to
      characterize binding sites on the target protein through frontal chromatographic
      and/or nonlinear chromatographic studies using a wide variety of ligands
      including small molecules and polypeptides. The columns have been used in drug
      discovery as well as in the screening of tobacco smoke condensates.

PMID- 19180088
TI  - Phenotyping sensory nerve endings in vitro in the mouse.
AB  - This protocol details methods to identify and record from cutaneous primary
      afferent axons in an isolated mammalian skin-saphenous nerve preparation. The
      method is based on extracellular recordings of propagated action potentials from
      single-fiber receptive fields. Cutaneous nerve endings show graded sensitivities
      to various stimulus modalities that are quantified by adequate and controlled
      stimulation of the superfused skin with heat, cold, touch, constant punctate
      pressure or chemicals. Responses recorded from single-fibers are comparable with
      those obtained in previous in vivo experiments on the same species. We describe
      the components and the setting-up of the basic equipment of a skin-nerve
      recording station (few days), the preparation of the skin and the adherent
      saphenous nerve in the mouse (15-45 min) and the isolation and recording of
      neurons (approximately 1-3 h per recording). In addition, stimulation techniques,
      protocols to achieve single-fiber recordings, issues of data acquisition and
      action potential discrimination are discussed in detail.

PMID- 19180090
TI  - Recombineering: a homologous recombination-based method of genetic engineering.
AB  - Recombineering is an efficient method of in vivo genetic engineering applicable
      to chromosomal as well as episomal replicons in Escherichia coli. This method
      circumvents the need for most standard in vitro cloning techniques.
      Recombineering allows construction of DNA molecules with precise junctions
      without constraints being imposed by restriction enzyme site location.
      Bacteriophage homologous recombination proteins catalyze these recombineering
      reactions using double- and single-stranded linear DNA substrates, so-called
      targeting constructs, introduced by electroporation. Gene knockouts, deletions
      and point mutations are readily made, gene tags can be inserted and regions of
      bacterial artificial chromosomes or the E. coli genome can be subcloned by gene
      retrieval using recombineering. Most of these constructs can be made within about
      1 week's time.

PMID- 19180092
TI  - Pairing cells to enhance fusion.

PMID- 19180091
TI  - Detection and quantification of viable airborne bacteria and fungi using solid
      phase cytometry.
AB  - This protocol describes the use of solid-phase cytometry for the enumeration of
      airborne bacteria and fungi. In contrast with conventional methods, accurate
      results can be obtained in real time, especially for air samples with low numbers
      of microorganisms. Air samples are collected by impaction on a water-soluble
      polymer that is subsequently dissolved. Part of the sample can be filtered over
      two membrane filters with different pore sizes. One filter is used to obtain a
      total count of all viable microorganisms, and a second filter is used to
      determine the number of airborne fungi. Microorganisms present on the filter are
      labeled with a viability substrate and subsequently detected and quantified using
      a solid-phase cytometer. The detected spots are microscopically validated using
      an epifluorescence microscope to discriminate between bacteria, fungi and
      fluorescent particles. The whole procedure takes 5 h to complete and results in
      the accurate quantification of airborne bacteria and fungi for samples with a low
      or high microbial load.

PMID- 19180093
TI  - Red lights, camera, photoactivation!

PMID- 19180096
TI  - 2008 FDA drug approvals.

PMID- 19180098
TI  - Deal watch: Bristol-Myers Squibb and Exelixis collaborate on kinase inhibitors.

PMID- 19180095
TI  - The molecular programme of tumour reversion: the steps beyond malignant
      transformation.
AB  - How cells become malignant has preoccupied scientists for over a century.
      However, the converse question is also valid: are tumour cells capable of
      reverting from their malignant state? Askanazy's studies in 1907 indicated that
      teratoma cells could differentiate into normal somatic tissues and current
      evidence indicates that some tumour cells have acquired the molecular circuitry
      that results in the negation of chromosomal instability, translocations, oncogene
      activation and loss of tumour suppressor genes. Studying these extremely rare
      events of tumour reversion and deciphering these pathways, which involve SIAH1,
      presenilin 1, TSAP6 and translationally controlled tumour protein (TCTP), could
      lead to new avenues in cancer treatment.

PMID- 19180099
TI  - Trial watch: Phase III promise for oral multiple sclerosis therapy.

PMID- 19180100
TI  - Regulatory watch: FDA issues guidance for cardiovascular risk assessment of novel
      antidiabetic agents.

PMID- 19180102
TI  - Mark McClellan.

PMID- 19180103
TI  - Systemic lupus erythematosus.

PMID- 19180104
TI  - Plerixafor.

PMID- 19180107
TI  - Response to 'Intermittent androgen blockade should be regarded as standard
      therapy in prostate cancer'.

PMID- 19180108
TI  - News the public should rely on.

PMID- 19180105
TI  - Mechanisms of drug combinations: interaction and network perspectives.
AB  - Understanding the molecular mechanisms underlying synergistic, potentiative and
      antagonistic effects of drug combinations could facilitate the discovery of novel
      efficacious combinations and multi-targeted agents. In this article, we describe
      an extensive investigation of the published literature on drug combinations for
      which the combination effect has been evaluated by rigorous analysis methods and
      for which relevant molecular interaction profiles of the drugs involved are
      available. Analysis of the 117 drug combinations identified reveals general and
      specific modes of action, and highlights the potential value of molecular
      interaction profiles in the discovery of novel multicomponent therapies.

PMID- 19180106
TI  - Knocking down barriers: advances in siRNA delivery.
AB  - In the 10 years that have passed since the Nobel prize-winning discovery of RNA
      interference (RNAi), billions of dollars have been invested in the therapeutic
      application of gene silencing in humans. Today, there are promising data from
      ongoing clinical trials for the treatment of age-related macular degeneration and
      respiratory syncytial virus. Despite these early successes, however, the
      widespread use of RNAi therapeutics for disease prevention and treatment requires
      the development of clinically suitable, safe and effective drug delivery
      vehicles. Here, we provide an update on the progress of RNAi therapeutics and
      highlight novel synthetic materials for the encapsulation and intracellular
      delivery of nucleic acids.

PMID- 19180109
TI  - New approaches in the potential treatment of HIV-acquired immunodeficiency
      disease.

PMID- 19180112
TI  - Intersection of gene therapy and progenitor cell biology in the lung.

PMID- 19180113
TI  - Casting doubt on the safety of "off-the-shelf" mesenchymal stem cells for cell
      therapy.

PMID- 19180116
TI  - DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes
      dissociation of beclin 1 from Bcl-XL and induction of autophagy.
AB  - Autophagy, an evolutionarily conserved process, has functions both in
      cytoprotective and programmed cell death mechanisms. Beclin 1, an essential
      autophagic protein, was recently identified as a BH3-domain-only protein that
      binds to Bcl-2 anti-apoptotic family members. The dissociation of beclin 1 from
      its Bcl-2 inhibitors is essential for its autophagic activity, and therefore
      should be tightly controlled. Here, we show that death-associated protein kinase
      (DAPK) regulates this process. The activated form of DAPK triggers autophagy in a
      beclin-1-dependent manner. DAPK phosphorylates beclin 1 on Thr 119 located at a
      crucial position within its BH3 domain, and thus promotes the dissociation of
      beclin 1 from Bcl-XL and the induction of autophagy. These results reveal a
      substrate for DAPK that acts as one of the core proteins of the autophagic
      machinery, and they provide a new phosphorylation-based mechanism that reduces
      the interaction of beclin 1 with its inhibitors to activate the autophagic
      machinery.

PMID- 19180117
TI  - Triggering the formation of tasiRNAs in Arabidopsis thaliana: the role of
      microRNA miR173.
AB  - Trans-acting small interfering RNAs (tasiRNAs) comprise a class of endogenous
      small RNAs that are generated from TAS gene-derived transcripts after these are
      cleaved at a microRNA (miRNA) target site. Arabidopsis thaliana has four families
      of TAS genes: miR173 triggers tasiRNA production from TAS1 and TAS2, miR390 from
      TAS3 and miR828 from TAS4. The two-hit trigger model postulates that dual target
      sites in the same transcript are often sufficient to initiate tasiRNA production,
      but two hits are not always required for tasiRNA formation. Here, we characterize
      the function of miR173 in the formation of tasiRNAs from TAS1 transcripts, as
      well as the importance of the TAS1 and TAS3 transcript sequences outside the
      miRNA-targeting sites for tasiRNA production. We show that tasiRNAs can be
      produced from heterologous transcripts containing miR173 or miR390 target sites,
      indicating that these trigger sequences are the only cis sequences essential for
      tasiRNA formation.

PMID- 19180118
TI  - IRX-2, a novel immunotherapeutic, protects human T cells from tumor-induced cell
      death.
AB  - IRX-2 is a cytokine-based biologic agent that has the potential to enhance
      antitumor immune responses. We investigated whether IRX-2 can protect T cells
      from tumor-induced apoptosis. Tumor-derived microvesicles (MV) expressing FasL
      were purified from supernatants of tumor cells and incubated with activated
      CD8(+) T cells. MV induced significant CD8(+) T-cell apoptosis, as evidenced by
      Annexin binding (64.4+/-6.4%), caspase activation (58.1+/-7.6%), a loss of
      mitochondrial membrane potential (82.9+/-3.9%) and DNA fragmentation. T-cell
      pretreatment with IRX-2 prevented apoptosis. IRX-2-mediated cytoprotection was
      dose and time dependent and was comparable to effects of IL-2, IL-7 or IL-15. IRX
      2 prevented MV-induced downregulation of JAK3 and TCRzeta chain and induced STAT5
      activation in T cells. IRX-2 prevented MV-induced Bax and Bim upregulation
      (P<0.005-0.05), prevented cytochrome c release and Bid cleavage, and concurrently
      restored the expression of Bcl-2, Bcl-xL, FLIP and Mcl-1 (P<0.005-0.01) in T
      cells. In addition, IRX-2 reversed MV-induced inhibition of the PI3K/Akt pathway.
      An Akt inhibitor (Akti-1/2) abrogated protective effects of IRX-2, suggesting
      that Akt is a downstream target of IRX-2 signaling. Thus, ex vivo pretreatment of
      CD8(+) T cells with IRX-2 provided potent protection from tumor-induced
      apoptosis. IRX-2 application to future cancer biotherapies could improve their
      effectiveness by bolstering T-cell resistance to tumor-induced immunosuppression.

PMID- 19180119
TI  - Amino acid 572 in TMC1: hot spot or critical functional residue for dominant
      mutations causing hearing impairment.
AB  - Two different missense mutations, p.D572N and p.D572H, affecting the same
      nucleotide and codon of the TMC1 gene were earlier reported to cause autosomal
      dominant hearing impairment at locus DFNA36 in two North American families. No
      other dominant mutations of human TMC1 have been published. We ascertained a
      third North American family segregating autosomal dominant nonsyndromic hearing
      impairment at the DFNA36 locus. We identified the p.D572N mutation of TMC1 co
      segregating with hearing loss in our study family. A comparative haplotype
      analysis of linked single nucleotide polymorphisms and short tandem repeats in
      the two families segregating p.D572N was not consistent with a founder effect.
      These findings can be explained in two ways. Either nucleotide 1714 is a hot spot
      for mutations or, alternatively, missense mutations at this site confer a
      specific pathogenic gain-of-function or dominant-negative effect.

PMID- 19180122
TI  - HUS/TTP update: 2008.

PMID- 19180120
TI  - Squamous morules are functionally inert elements of premalignant endometrial
      neoplasia.
AB  - Squamous morules are a common component of premalignant glandular lesions that
      are followed by glandular, rather than squamous, carcinomas. We tested the
      hypothesis that the appearance of glands associated with morules predicts cancer
      risk, and undertook molecular testing to determine the clonal and hormonal
      response properties of admixed squamous and glandular elements. A total of 66
      patients with squamous morules in an index endometrial biopsy had follow-up
      clinical data (average follow-up: interval 31 months, 2.5 biopsies) showing
      development of carcinoma in 11% (7/66) of cases. The histological appearance of
      morule-associated glands in the index biopsy was significantly associated with
      this clinical outcome, with the majority (71%, 5/7) of cancer occurrences
      following an overtly premalignant lesion (endometrial intraepithelial neoplasia)
      with squamous morules. Eight endometrial intraepithelial neoplasias with squamous
      morules were examined by immunohistochemistry for estrogen and progesterone
      receptors and mitotic activity (Ki-67 antigen percent stained). Glandular
      components had abundant estrogen and progesterone receptors, and high levels of
      mitotic activity in all cases. In sharp contrast, all squamous morules were
      devoid of sex hormone receptors and had undetectable or extremely low
      proliferation rates. When mutated, the same specific PTEN mutation was detected
      in squamous and glandular elements, indicating that both are of common lineage.
      The clinical and laboratory data are consistent with a model of morule biology in
      which squamous morules are a hormonally incompetent subpopulation of endometrial
      glandular lesions. Isolated morules might result from artifactual displacement
      from their native glandular context, or selective hormonally induced regression
      of the glandular but not squamous components over time. Subsequent cancer risk,
      as promoted by estrogens, is greatest when the glandular component has the
      appearance of endometrial intraepithelial neoplasia. Even isolated morules should
      be carefully followed, however, to exclude a coexisting undersampled, or occult,
      glandular lesion.

PMID- 19180123
TI  - Mechanisms of microvascular thrombosis in thrombotic thrombocytopenic purpura.
AB  - Recent studies have demonstrated that thrombotic thrombocytopenic purpura (TTP),
      a serious thrombotic disorder affecting the arterioles and capillaries of
      multiple organs, is caused by a profound deficiency in the von Willebrand factor
      cleaving metalloprotease, ADAMTS13. ADAMTS13, a 190-kD plasma protease
      originating primarily in hepatic stellate cells, prevents microvascular
      thrombosis by cleaving von Willebrand factor when the substrate is
      conformationally unfolded by high levels of shear stress in the circulation.
      Deficiency of ADAMTS13, due to genetic mutations or inhibitory autoantibodies,
      leads to accumulation of superactive forms of vWF, resulting in vWF-platelet
      aggregation and microvascular thrombosis. Analysis of ADAMTS13 has led to the
      recognition of subclinical TTP and atypical TTP presenting with thrombocytopenia
      or acute focal neurological deficits without concurrent microangiopathic
      hemolysis. Infusion of plasma replenishes the missing ADAMTS13 and ameliorates
      the complications of hereditary TTP. The patients are at risk of both acute and
      chronic renal failure if they receive inadequate plasma therapy. The more
      frequent, autoimmune type of TTP requires plasma exchange therapy and perhaps
      immunomodulatory measures. Current studies focus on the factors affecting the
      phenotypic severity of TTP and newer approaches to improving the therapies for
      the patients.

PMID- 19180124
TI  - Mechanism of microthrombosis in HUS.
AB  - The mechanism of formation of the microthrombi in hemolytic uremic syndrome (HUS)
      is not known. Plasma from five adult and six pediatric cases of HUS showed
      aggregation and release of adenosine triphosphate from normal platelets. When the
      plasma was absorbed with staphylococcal protein A and again exposed to normal
      platelets there was no aggregation or release, indicating that an antibody was
      responsible for the aggregation. The plasma reacted with platelet lysate in a
      western blot, showing reactivity with CD36. This was confirmed by probing with
      Mo91, a monoclonal antibody to CD36. When the patient's plasma was used to probe
      purified verotoxin-2, bands of 32 and 7.7 kDa were obtained. Similar results were
      obtained using Mo91. The reactions suggest structural homologies between CD36 and
      verotoxin. Although a direct cause-effect relationship is not yet established,
      the data support the concept of an immunological pathogenesis for HUS with the
      formation of cross-reacting antibodies.

PMID- 19180125
TI  - Verotoxin biology: molecular events in vascular endothelial injury.
AB  - Escherichia coli-derived verotoxins (VTs) play a critical role in the
      pathogenesis of hemolytic uremic syndrome (HUS) in major part due to vascular
      endothelial damage. Perturbations in endothelial phenotype account for many of
      the clinical features observed in patients. VTs inactivate host cell ribosomes
      and prevent protein synthesis. Interestingly, however, they also dramatically
      alter gene expression at concentrations that have only minor effects on overall
      mRNA translation. Using endothelin-1 as a model, we describe the molecular
      mechanisms by which VT alters the endothelial cell phenotype in HUS. RNA
      metabolism pathways and effects on translation may play central roles in the
      molecular events operative in vascular injury mediated by these potent bacteria
      derived exotoxins.

PMID- 19180127
TI  - Experiences with HUS in Canada: what have we learned about childhood HUS in
      Canada?
AB  - Experiences with childhood hemolytic uremic syndrome (HUS) in Canada will focus
      on the development of the Canadian Pediatric Kidney Disease Research Centre
      (CPKDRC) and the results of our collaborative research over a 13-year period
      (1985-1998).

PMID- 19180128
TI  - Shiga toxin-associated hemolytic uremic syndrome and thrombotic thrombocytopenic
      purpura: distinct mechanisms of pathogenesis.
AB  - The hemolytic uremic syndrome (HUS) of childhood is, in its most common form, a
      non-immune microangiopathic hemolytic anemia. HUS typically follows an enteric
      infection with a Shiga toxin-producing Escherichia coli, usually belonging to
      serotype O157:H7. The antecedent infection is almost always manifested as non
      bloody diarrhea. In about 80% of cases, the diarrhea becomes bloody between one
      and five days after the onset of diarrhea. The courses of acute gastrointestinal
      infections, and of HUS, in adults and children are similar. There are no
      convincing data that this easily recognizable form of microangiopathy is related
      to any inborn or acquired deficiency of ADAMTS13, and plasma therapies are not
      justified on either theoretical or empirical grounds. Similarly, there are no
      realistic animal data to support use of plasma exchange or infusion in children
      or adults with, or at risk for, HUS secondary to gastrointestinal infection with
      E. coli O157:H7. Best clinical practices involve rapid and accurate clinical and
      microbiological identification of infected patients, volume expansion, and
      support of the intestinal and extraintestinal complications that can ensue during
      acute enteric infection and associated HUS. Clinical clues include a sequence of
      events where the stool becomes bloody after a several-day interval of bloody
      diarrhea, considerable abdominal pain, five or more stools in the 24 h before
      presentation, pain on defection, and absence of fever at the time of
      presentation. Diagnosis should rely primarily on sorbitol MacConkey agar culture.
      Shiga toxin testing should not be used as the only screen to identify infected
      patients.

PMID- 19180126
TI  - Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura
      (TTP): review of clinical, laboratory, epidemiological, and pharmacovigilance
      findings (1989-2008).
AB  - Thrombotic thrombocytopenic purpura (TTP) is a fulminant disease characterized by
      platelet aggregates, thrombocytopenia, renal insufficiency, neurologic changes,
      and mechanical injury to erythrocytes. Most idiopathic cases of TTP are
      characterized by a deficiency of ADAMTS13 (a disintegrin and metalloprotease,
      with thrombospondin-1-like domains) metalloprotease activity. Ironically, use of
      anti-platelet agents, the thienopyridine derivates clopidogrel and ticlopidine,
      is associated with drug induced TTP. Data were abstracted from a systematic
      review of English-language literature for thienopyridine-associated TTP
      identified in MEDLINE, EMBASE, the public website of the Food and Drug
      Administration, and abstracts from national scientific conferences from 1991 to
      April 2008. Ticlopidine and clopidogrel are the two most common drugs associated
      with TTP in FDA safety databases. Epidemiological studies identify recent
      initiation of anti-platelet agents as the most common risk factor associated with
      risks of developing TTP. Laboratory studies indicate that most cases of
      thienopyridine-associated TTP involve an antibody to ADAMTS13 metalloprotease,
      present with severe thrombocytopenia, and respond to therapeutic plasma exchange
      (TPE); a minority of thienopyridine-associated TTP presents with severe renal
      insufficiency, involves direct endothelial cell damage, and is less responsive to
      TPE. The evaluation of this potentially fatal drug toxicity can serve as a
      template for future efforts to comprehensively characterize other severe adverse
      drug reactions.

PMID- 19180129
TI  - Factors that led to the Walkerton tragedy.
AB  - In May 2000, bacterial contamination of municipal water in Walkerton, Ontario,
      resulted in the worst public health disaster involving municipal water in
      Canadian history. At least seven people died and 2300 became ill. A public
      inquiry led by judge Dennis O'Connor examined the events and delineated the
      causes of the outbreak, including physical causes, the role of the public
      utilities operators, the public utilities commissioners, the Ministry of the
      Environment (MOE), and the provincial government. Improper practices and systemic
      fraudulence by the public utility operators, the recent privatization of
      municipal water testing, the absence of criteria governing quality of testing,
      and the lack of provisions made for notification of results to multiple
      authorities all contributed to the crisis. The MOE noted significant concerns 2
      years before the outbreak; however, no changes resulted because voluntary
      guidelines as opposed to legally binding regulations governed water safety. The
      inquiry concluded that budgetary restrictions introduced by the provincial
      government 4 years before the outbreak were enacted with no assessment of risk to
      human health. The ministers and the cabinet had received warnings about serious
      risks. Budgetary cuts destroyed the checks and balances that were necessary to
      ensure municipal water safety.

PMID- 19180130
TI  - An outbreak of diarrhea-associated childhood hemolytic uremic syndrome: the
      Walkerton epidemic.
AB  - In Canada, the majority of cases of childhood hemolytic uremic syndrome (HUS) are
      associated with a diarrheal illness (D+) due to verotoxin-producing Escherichia
      coli (VTEC). Although the ingestion of undercooked beef is an important cause, we
      report on the largest outbreak of E. coli illness due to a contaminated supply of
      municipal water. We describe the clinical features and short-term outcomes of 22
      children who simultaneously developed D+HUS.

PMID- 19180131
TI  - Renal prognosis of toxigenic Escherichia coli infection.
AB  - There is a spectrum of acute illness for individuals who ingest toxigenic
      Escherichia coli, ranging from no symptoms to self-limited gastroenteritis, to
      full acute hemolytic uremic syndrome. Knowledge of the long-term prognosis of
      acute toxigenic E. coli ingestion, based on the presentation of acute illness, is
      important for patient counseling and follow-up. Here, we consider subsequent 5
      year renal outcomes for groups of individuals who presented across a spectrum of
      acute illness during a municipal water outbreak of E. coli O157:H7 in Walkerton,
      Canada.

PMID- 19180132
TI  - Host and pathogen determinants of verocytotoxin-producing Escherichia coli
      associated hemolytic uremic syndrome.
AB  - Verocytotoxin (VT)-producing Escherichia coli (VTEC) infection is associated with
      a spectrum of clinical manifestations that includes diarrhea, hemorrhagic
      colitis, and the hemolytic uremic syndrome (HUS). The occurrence of HUS in a
      minority of individuals in outbreaks of VTEC infection is a function of several
      pathogen and host factors. Pathogen factors include the inoculum size and
      serotype of the infecting strain, horizontally acquired genetic elements known as
      pathogenicity islands, and probably the VT type. Host factors that increase the
      risk of developing HUS include age, pre-existing immunity, gastric acidity, the
      use of antibiotics and anti-motility agents, and, probably, stress and genetic
      factors that modulate host response to infection, such as innate immunity and
      toxin receptor type, expression, and distribution. A better understanding of the
      pathogen and host determinants of HUS can aid in the development of more
      effective public health strategies to reduce the risk of developing HUS.

PMID- 19180133
TI  - Post-infectious irritable bowel syndrome following water contamination.
AB  - Post-infectious irritable bowel syndrome (PI-IBS) is a common disorder wherein
      symptoms of IBS begin after an episode of acute gastroenteritis. The Walkerton
      Health Study (WHS) was initiated in 2002 to study the long-term outcomes of
      tragic contamination of its municipal water supply with Escherichia coli and
      Campylobacter species in 2000. Within a cohort of 2069 adult Walkerton residents
      with no prior history of chronic gastrointestinal disorders, the incidence of PI
      IBS 2 years after the outbreak was 10.1% among subjects with no acute
      gastroenteritis vs 36.2% among those with clinically suspected gastroenteritis
      (P<0.001). Long-term follow-up of the WHS cohort has shown PI-IBS to have a
      favorable prognosis, with spontaneous remission in most patients. A recent meta
      analysis of nine cohort studies estimated the pooled odds ratio for developing
      IBS after enteric infection to be 5.86 (95% CI 3.60-9.54). Risk factors for PI
      IBS include female gender, younger age, more severe acute enteric infection, and
      psychiatric comorbidity. A prevailing hypothesis is that PI-IBS results from a
      failure to downregulate inflammation after an acute insult from gastroenteritis,
      a model supported by preliminary studies of intestinal permeability and pro
      inflammatory genotypes. Ongoing research is testing the hypothesis that PI-IBS
      denotes increased susceptibility to more overt inflammatory disorders such as
      Crohn's disease. Although the Walkerton outbreak of acute gastroenteritis was an
      awful human tragedy, it is hoped that the WHS will advance our understanding of
      PI-IBS and improve the outcomes of people who suffer similar tragedies in the
      future.

PMID- 19180134
TI  - Relationship between Escherichia coli O157:H7 and diabetes mellitus.
AB  - Ingestion of Escherichia coli O157:H7 can cause a spectrum of acute illness,
      ranging from overt hemolytic-uremic syndrome (HUS), to gastroenteritis with
      bloody diarrhea, to no symptoms. This organism has been responsible for dozens of
      outbreaks of gastroenteritis and HUS in industrialized nations, and thus is a
      major public health concern. Although the acute effects of E. coli O157:H7
      ingestion are well understood, the long-term complications are less well known.
      Here, we review the biological and empirical evidence supporting a link between
      E. coli O157:H7 and long-term diabetes mellitus. Survivors with diarrhea
      associated HUS have a significantly increased incidence of diabetes due to
      complete insulin deficiency, which may recur several years after the initial
      infection. However, less severe forms of infection, such as E. coli O157:H7
      gastroenteritis without overt HUS, do not appear to result in an increased risk
      of type 2 diabetes.

PMID- 19180135
TI  - Risk of pregnancy-related hypertension within five years of exposure to bacteria
      contaminated drinking water.
AB  - Exposure to Escherichia coli O157:H7 may result in subclinical kidney injury
      manifesting as hypertension during pregnancy. We evaluated the risk of pregnancy
      related hypertension (PRH) among previously healthy females from the Walkerton
      Health Study, Canada (2002-6), who conceived within five years of exposure to
      bacteria-contaminated drinking water. Ontario Ministry of Health Antenatal forms
      were used to determine outcomes and risk factors. PRH was defined as any systolic
      or diastolic blood pressure (BP) > or =140 mm Hg and > or =90 mm Hg,
      respectively. Chronic and gestational hypertension were defined, respectively, as
      elevated BP observed prior to or at > or =20 weeks gestation. Risk of PRH was
      evaluated using a modified Poisson regression model that controlled for known
      risk factors. Of 148 eligible pregnancies, antenatal audits with blood pressure
      data were available for 135. PRH was detected in 20.7% pregnancies, of which 6.7%
      were chronic hypertension and 14.1% gestational hypertension. Although
      nonsignificant, we observed a consistent trend toward higher rates of PRH and
      mean arterial pressure, particularly prior to 20 weeks gestation, among women who
      reported symptomatic gastroenteritis compared to asymptomatic women. BP should be
      monitored closely in women after exposure to contaminated water.

PMID- 19180136
TI  - TTP/HUS: observational studies generate hypotheses that lead to randomized
      controlled trials.
AB  - Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) is a
      disease syndrome, and its history exemplifies how small observational studies
      lead to hypotheses that spawn randomized control trials (RCTs). Moschowitz's
      original case report coupled with the case findings of Bukowski and Byrne led to
      the RCT of Rock and the Canadian Apheresis Group that proved plasma exchange was
      superior to plasma infusion for the treatment of adults with TTP/HUS. Our single
      case report of continuous plasma exchange coupled with the observations about the
      pathogenic role of von Willebrand multimer protease of Tsai and Furlan
      strengthened by a 25-year observational study of plasma exchange treatment for
      TTP/HUS has led to a proposal to initiate a new RCT.

PMID- 19180137
TI  - The thrombotic thrombocytopenic purpura and hemolytic uremic syndromes:
      evaluation, management, and long-term outcomes experience of the Oklahoma TTP-HUS
      Registry, 1989-2007.
AB  - The Oklahoma thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP
      HUS) Registry, an inception cohort of 382 consecutive patients with TTP-HUS,
      provides a complete community perspective of these syndromes. TTP, as defined by
      thrombocytopenia and microangiopathic hemolytic anemia without an alternative
      etiology, is the appropriate term for all adults. These limited diagnostic
      criteria are supported by the presenting features of patients with ADAMTS13
      deficiency, in whom both neurologic and renal abnormalities are uncommon. HUS is
      the appropriate term for children who fulfill these diagnostic criteria and who
      also have renal failure. These definitions are consistent with current
      management: plasma exchange is the essential treatment for most adults;
      supportive care is sufficient for children with HUS. Plasma exchange treatment
      has decreased the mortality of TTP from 90 to 10%. Patients with acquired
      autoimmune ADAMTS13 deficiency may also require immunosuppressive treatment to
      achieve a durable remission. Recovery has revealed previously unrecognized long
      term risks. Recurrent acute episodes occur in approximately 40% of patients with
      acquired ADAMTS13 deficiency; most relapses occur within the first year and most
      patients have only one relapse. Adults with TTP of any etiology have a high risk
      for persistent minor cognitive abnormalities.

PMID- 19180139
TI  - TTP/HUS and prognosis: the syndrome and the disease(s).
AB  - Patients presenting with the syndrome of microangiopathic hemolysis and
      thrombocytopenia, without Shiga toxin-associated colitis, have thrombotic
      thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Prognosis for
      TTP/HUS has changed over time from a fatal disorder associated with the classic
      pentad to a syndrome associated with 80% survival in the plasma exchange era. A
      growing number of mechanisms, including but not exclusive to severe ADAMTS13
      deficiency, are now understood to result in this syndrome, and the prognosis of
      patients with TTP/HUS is related to many additional factors. This update on
      prognosis explores recent registry data studying both acquired idiopathic and
      also familial or recurrent forms of TTP/HUS, to delineate how mortality varies by
      underlying disease mechanism. This paper also explores the association between
      mortality and clinical presenting features, as well as whether the case is a
      primary or relapsed presentation. Recent data support an understanding of TTP/HUS
      as a heterogeneous syndrome with variable mortality, and with specific subgroups
      demonstrating an excellent outcome.

PMID- 19180138
TI  - A Canadian phase II study evaluating the efficacy of rituximab in the management
      of patients with relapsed/refractory thrombotic thrombocytopenic purpura.
AB  - Rituximab is a chimeric monoclonal antibody that targets the human CD-20 antigen
      present on malignant and normal B lymphocytes. Recent clinical studies have shown
      a significant response rate when this drug is given to selected patients with
      thrombotic thrombocytopenic purpura (TTP). Given that the clinical manifestations
      of TTP may be the direct result of an auto-antibody against a regulatory Von
      Willebrand factor enzyme (ADAMTS13), it makes biological sense to consider a
      therapy that has the ability to diminish or eradicate antibody-producing B cells.
      Despite initial positive results, there is a need to identify which patients
      derive durable benefit from this agent. As in other conditions that utilize
      therapeutic immunosuppression, there is a risk that the addition of rituximab may
      also lead to serious opportunistic infections.

PMID- 19180140
TI  - Treatment options for HUS secondary to Escherichia coli O157:H7.
AB  - Shiga toxin (Stx)-producing Escherichia coli (STEC)-induced enteropathic HUS
      (eHUS) is a major cause of acute kidney injury in children and substantial
      morbidity and mortality in elderly patients. Systemic intestinal absorption of
      Stx and rapid uptake, through its glycolipid receptor (Gb3), by small vessel
      endothelial cells, are essential steps in the pathophysiology of STEC disease.
      HUS is characterized by intravascular hemolytic anemia, thrombocytopenia and
      acute kidney injury (AKI) that develop abruptly within a week of onset of STEC
      diarrhea/colitis. Subtle thrombotic changes, attributed to Stx-mediated
      endothelial injury, may not be limited to HUS. Current treatment of STEC disease
      targets gastrointestinal, hematological, vascular and renal complications. It
      includes isotonic volume replacement/expansion, red blood cell and platelet
      transfusion and, for severe AKI, hemo- or peritoneal dialysis. Plasma exchange is
      not indicated for eHUS. Novel strategies are being designed for disease
      prevention or amelioration, including STEC-component vaccines (Stx, protective
      antigens), toxin neutralizers (Stx-neutralizing monoclonal antibodies [STmAb],
      Gb3 mimics), and small molecules that block Stx-induced, pathogenic cellular
      pathways of cell activation/apoptosis. Receptor mimics and STmAb, given
      parenterally up to 48-72 h after oro-gastric infection, protect experimental
      animals from otherwise lethal outcomes. Phase II/III mAb studies are planned;
      however, the narrow, hypothetical therapeutic window makes treatment trials
      challenging.

PMID- 19180141
TI  - The thrombotic thrombocytopenic purpura and hemolytic uremic syndromes: overview
      of pathogenesis (Experience of The Oklahoma TTP-HUS Registry, 1989-2007).
AB  - The Oklahoma TTP (thrombotic thrombocytopenic purpura)-HUS (hemolytic uremic
      syndrome) Registry, an inception cohort of 382 consecutive patients with TTP-HUS,
      provides a complete community perspective of these syndromes. TTP is the
      diagnostic term used for all adults, with or without neurologic or renal
      abnormalities; it is typically an acquired disorder; it may rarely result from
      congenital ADAMTS13 deficiency. HUS is the term used for children who have renal
      failure, most often caused by Escherichia coli O157:H7 infection; it may rarely
      result from congenital abnormalities of complement regulation. Clinical
      categories related to associated conditions and potential etiologies provide a
      structure for describing pathogenesis of the acquired syndromes. (1) Following
      allogeneic hematopoietic stem cell transplantation; a disorder primarily
      affecting kidneys described as transplantation-associated thrombotic
      microangiopathy. (2) Pregnancy-associated; pregnancy is a prominent risk factor
      for the development of TTP. (3) Drug-associated; acute, immune-mediated systemic
      syndromes and also dose-dependent renal toxicity. (4) Bloody diarrhea prodrome,
      suggesting an enteric infectious etiology. (5) Presence of an additional
      autoimmune disorder. (6) Idiopathic. A severe deficiency of ADAMTS13 activity
      contributes to the pathogenesis of many idiopathic patients and also some
      patients who present during pregnancy, with bloody diarrhea, or who have
      additional autoimmune disorders.

PMID- 19180142
TI  - NT-polyplex: a new tool for therapeutic gene delivery to neuroblastoma tumors.
AB  - Neurotensin (NT)-polyplex is a nonviral system for the targeted gene delivery to
      cells that express and internalize the high-affinity NT receptor (NTSR1). In
      hemiparkinsonian rats, we previously demonstrated the morphological and
      functional recovery from dopaminergic neurodegeneration using the NT-polyplex as
      a vehicle to transfect a neurotrophic gene. The main objective of this work was
      to demonstrate the feasibility of NT-polyplex to transfect reporter or
      therapeutic genes into neuroblastoma tumors through the blood stream or by
      intratumoral injection. N1E-115 cells known to express NTSR1 were allografted
      into athymic mice to generate the neuroblastoma tumor model. Both routes of
      administration allowed the NT-polyplex to reach and transfect tumoral cells. A
      low transgene expression was also detected in intestinal tract cells only after
      the injection into the blood stream. The transfection of the thymidine kinase
      (HSVTK) suicide gene followed by ganciclovir (GCV) treatment decreased the size
      and weight of neuroblastoma tumors by 30-50% and increased apoptosis compared to
      controls. This study shows the potential of the NT-polyplex as specific gene
      transfer system for NTSR1 cancer cells.

PMID- 19180143
TI  - M-PEIs nanogels: potential nonviral vector for systemic plasmid delivery to tumor
      cells.
AB  - Successfully systemic gene therapy has been hindered by vector-related
      limitations, including toxicity and inefficient gene delivery to tumor cells
      after intravenous administration. In this study, we evaluated the potential of
      spherical polyethylenimine nanogels (M-PEIs) as a novel vector for intravenous
      delivery of plasmids to tumor cells. M-PEIs provided a sustained release of
      plasmids up to 14 days and were also effective in protecting plasmids from
      enzymatic degradation in serum-conditioned media. M-PEIs showed no obvious
      cytotoxicity to mammalian cells in vitro as well as to liver, heart and kidney in
      mice after intravenous injection. Importantly, following intravenous
      administration of M-PEIs/plasmid complexes into human hepatocellular carcinoma
      xenograft-bearing mice, green fluorescence protein reporter gene expression was
      predominantly found in the tumor. This study indicates that M-PEIs may be a
      candidate for systemic delivery of plasmids into tumors.

PMID- 19180144
TI  - Fiber-chimeric adenoviruses expressing fibers from serotype 16 and 50 improve
      gene transfer to human pancreatic adenocarcinoma.
AB  - Survival of patients with pancreatic cancer is poor. Adenoviral (Ad) gene therapy
      employing the commonly used serotype 5 reveals limited transduction efficiency
      due to the low amount of coxsackie-adenovirus receptor on pancreatic cancer
      cells. To identify fiber-chimeric adenoviruses with improved gene transfer, a
      library of Ad vectors based on Ad5 and carrying fiber molecules consisting of 16
      other serotypes were transduced to human pancreatic carcinoma cell lines.
      Adenoviruses containing fibers from serotype 16 and 50 showed increased gene
      transfer and were further analyzed. In a gene-directed prodrug activation system
      using cytosine deaminase, these adenoviruses proved to be effective in
      eradicating primary pancreatic tumor cells. Fiber-chimeric Ad5 containing fiber
      16 and wild-type Ad5 were also transduced ex vivo to slices of normal human
      pancreatic tissue and pancreatic carcinoma tissue obtained during surgery. It was
      shown that fiber-chimeric Ad5 with fiber 16 revealed an improved gene delivery to
      primary pancreatic tumor tissue compared to Ad5. In conclusion, fiber-chimeric
      adenoviruses carrying fiber 16 and 50 reveal a significantly enhanced gene
      transfer and an increased specificity to human pancreatic adenocarcinoma compared
      to Ad5, whereas transduction to normal pancreatic tissue was decreased. These
      findings expand the therapeutic window of Ad gene therapy for pancreatic cancer.

PMID- 19180146
TI  - Medicine and art: one culture?

PMID- 19180148
TI  - To see a world in a grain of sand: elucidating the pathophysiology of Anderson
      Fabry disease through investigations of a cellular model.
AB  - Thomaidis and colleagues have created a cellular model of Anderson-Fabry disease
      by 'silencing' alpha-galactosidase A (AGAL) activity in human tubular epithelial
      cells. Increased membrane globotriaosylceramide (Gb3/CD77) expression was
      observed; it is suggested that this finding may be potentially useful as a
      surrogate marker of disease severity. Decreased membrane Gb3/CD77 expression was
      observed following agalsidase-alpha treatment, providing evidence of changes in
      cellular phenotype in response to enzyme therapy.

PMID- 19180149
TI  - Collapsing glomerulopathy: beyond serendipity in mouse genetics.
AB  - Clinical correlates suggest that collapsing glomerulopathy results from the
      pathogenic interaction between patients' intractable genetic susceptibilities and
      environmental insults. When the environmental insults include a virus that
      introduces its own pathogenic genes, the interactions become more complex. Chan
      et al. combine reverse and forward genetic techniques in mice toward
      understanding this complexity with HIV and identify candidate genetic modifiers
      of collapsing glomerulopathy.

PMID- 19180152
TI  - Could N-terminal pro-BNP peptide be a useful marker for prediction of cardiac
      arrests in hemodialysis patients?

PMID- 19180150
TI  - Lanthanum and phosphate: science, policy, and survival.
AB  - Mineral metabolism in chronic kidney disease is attracting intense interest and
      unprecedented levels of research. The pharmaceutical industry has responded by
      developing various new agents. Bervoets et al. report the use of an unusual
      combination of basic-science techniques to increase understanding of the kinetics
      of one such agent--lanthanum carbonate--in the gastrointestinal tract and liver.
      However, do we need to answer more fundamental clinical questions before we can
      definitively identify the role of similar new and expensive drugs?

PMID- 19180154
TI  - Not all new recombinant human erythropoietins are biosimilars.

PMID- 19180155
TI  - Hormone therapy and loss of kidney function.

PMID- 19180156
TI  - The case. Hypokalemia associated with nephrocalcinosis. Distal renal tubular
      acidosis associated with Sjogren's syndrome.

PMID- 19180157
TI  - Vicarious contrast excretion by the gallbladder in contrast nephropathy.

PMID- 19180158
TI  - [What does the Tidsskriftet's editorial committee do?].

PMID- 19180159
TI  - [Carpal fractures--time for new practice!].

PMID- 19180160
TI  - [Cast immobilisation for suspected scaphoid fractures].
AB  - BACKGROUND: Patients with suspected scaphoid fractures usually have their arm
      immobilised in a cast for two weeks, even in the absence of radiographic signs of
      fracture. After two weeks a new radiographic examination is performed. Our
      objective was to assess the extent of unnecessary cast immobilisation and to
      describe existing diagnostic practice in our hospital. MATERIAL AND METHODS: We
      performed a retrospective study to identify all patients treated for suspected
      scaphoid fracture in our hospital in the period 2001 - 2006. The extent of
      unnecessary immobilisation and the use of diagnostic procedures were assessed by
      systematic review of patients' medical records. RESULTS: 45 of 194 patients
      treated as if they had a scaphoid fracture were diagnosed with a fracture; 29 by
      plain radiographs at the first consultation and 16 at later consultations (nine
      by plain radiographs after two weeks, three by MRI after two weeks and four by
      repeated clinical assessments for maximum 10 weeks). 89 patients of working age
      and without scaphoid fracture were treated with cast immobilisation for 187 weeks
      in total. INTERPRETATION: Only 23 % of patients treated with cast immobilisation
      for two weeks were ultimately diagnosed with scaphoid fracture. The extent of
      unnecessary cast immobilisation indicates a need to use better diagnostic tools
      early after the injury.

PMID- 19180162
TI  - [Treatment of carpal fractures].
AB  - BACKGROUND: The aim of this study was to elucidate the incidence and treatment of
      patients with carpal bone fractures at a county hospital in Norway. MATERIAL AND
      METHODS: 320 patients with 331 carpal bone fractures treated at the The Hospital
      of Haugesund, Norway are included in this study. Information was gathered from
      patient records. RESULTS: 277 patients had scafoid fractures and ultimately 95.8
      % healed. 243 patients with a scafoid fracture were immediately treated with
      plaster-immobilization or operatively because of major dislocation and 89 %
      healed. The patients with a non-union underwent surgery and ultimately 98.7 %
      healed in this group. 34 patients suffered delayed treatment and following
      immobilization and operative treatment healing ensued in only 75 % of these
      fractures. Inadequate or delayed treatment resulted in a significantly higher
      rate of non-union and surgery. All 54 non-scafoid fractures healed satisfactory
      and only one was operated. 27 patients had fractures of the triquetrum; fractures
      of the six remaining carpal bones were rare. INTERPRETATION: The results of
      primary plaster immobilisation and primary operative treatment were considered
      satisfactory. Our results compare well with other reports.

PMID- 19180161
TI  - [Nephrogenic systemic fibrosis and use of MR contrast media].
AB  - BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a new and probably iatrogenic
      disorder. It was first described time in 2000 and associated with the use of
      gadolinium containing MR contrast media in patients with impaired renal function
      in 2006. MATERIAL AND METHOD: We describe a case of NSF identified at Haukeland
      University Hospital and give a brief overview of the disease, based on literature
      retrieved from a non-systematic search. RESULTS AND INTERPRETATION: NSF is a
      serious systemic disorder with active inflammation and fibrosis, particularly in
      skin, but also in other tissue such as skeletal muscle, heart and oesophagus. The
      condition is very difficult to treat. Awareness of the illness has led to changes
      in guidelines and clinical practice regarding use of gadolinium-containing
      contrast media in patients with renal impairment.

PMID- 19180163
TI  - [Pregabalin and its potential for abuse].
AB  - The aim of this paper is to assess the substance pregabaline's potential for
      abuse. Little information is available on the subject and that retrieved is in
      part conflicting. Pregabaline is likely to be abused for its positive
      psychological effects, e.g. euphoria. However, these effects are weak and not
      sustained during long-term use. Pregabaline is therefore likely to have a lower
      potential for abuse than benzodiazepines. In clinical studies, symptoms
      suggestive of physical dependence (e.g. insomnia, nausea, headache, diarrhoea)
      have been observed in some patients after abrupt discontinuation of pregabaline.
      However, available documentation indicates that pregabaline is associated with
      less physical and psychological dependence than benzodiazepines.

PMID- 19180164
TI  - [The meningococcal vaccine trial 1988-91].

PMID- 19180166
TI  - [Is good communication so difficult?].

PMID- 19180170
TI  - Aza- and Carbo-[3 + 3] Annulations of Exo-Cyclic Vinylogous Amides and Urethanes.
      Synthesis of Tetrahydroindolizidines and An Unexpected Formation of
      Hexahydroquinolines.
AB  - [3 + 3] Annulations of exo-cyclic vinylogous amides and urethanes with vinyl
      iminium salts are described here. We observed an intriguing dichotomy in their
      reaction pathways. For pyrrolidine- and azepane-based vinylogous amides or
      urethanes, aza-[3 + 3] annulation would dominate to give tetrahydroindolizidines,
      whereas, unexpectedly, for piperidine-based vinylogous amides or urethanes, carbo
      [3 + 3] annulation was the pathway, leading to hexahydroquinolines. The origin
      for such a contrast is likely associated with a switch in the initial reaction
      pathway between C-1,2-addition and C-1,4-addition.

PMID- 19180171
TI  - alpha-Amino 1,3-Dithioketal Mediated Asymmetric Synthesis of Piperidines (L
      733,060) and Tetrahydrofuran Glycines.
AB  - Sulfinimine-derived alpha-amino 1,3-dithianes, alpha-amino carbonyl chiral
      building blocks, are utilized in asymmetric syntheses of (+)-(tetrahydrofuran-2
      yl)glycine and the 2,3-disubstituted piperidine (+)-L-733,060.

PMID- 19180172
TI  - Central-to-Axial Chirality Transfer in the Benzannulation Reaction of Optically
      Pure Fischer Carbene Complexes in the Synthesis of Allocolchicinoids.
AB  - A method for the synthesis of allocolchicinoids is explored that involves the
      benzannulation reaction of Fischer chromium carbene complexes with alkynes. The
      benzannulation reaction is employed to install the aromatic C-ring via the
      reaction of an alpha,beta-unsaturated carbene complex in which the carbene
      complex is attached to a seven-membered ring that is to become the B-ring of the
      allocolchicinoids. Two different regioisomeric series can be accessed depending
      on which position the carbene complex is on the seven membered ring. A key issue
      that is addressed is the stereochemistry of the newly formed axis of chirality
      that results from a stereo-relay from an existing chiral center on the seven
      membered ring at the position destined to be C(7) in the allocolchicinoids. The
      level of stereochemistry is dependent on the position of the carbene complex on
      the seven membered ring. A mechanism is proposed to account for this
      stereochemical dependence and to account for the observed effects of temperature
      and solvent on the stereoselectivity. Finally, the benzannulation reactions of
      optically pure complexes are examined and quite surprisingly one, but not both,
      of the diastereomeric products is racemized. The racemization can be prevented
      with the proper choice of solvent and temperature. A mechanism is proposed to
      account for the racemization of only one of the diastereomers of the product that
      involves the intermediacy of an ortho-quinone methide chromium tricarbonyl
      complex.

PMID- 19180173
TI  - A benzannulation strategy for the synthesis of phenols and heteroaromatic
      compounds based on the reaction of (trialkylsilyl)vinylketenes with lithium
      ynolates.
AB  - (Trialkylsilyl)vinylketenes react with lithium ynolates to generate 3
      (oxido)dienylketenes which undergo rapid 6pi-electrocyclization. The ultimate
      products of this benzannulation are highly substituted resorcinol monosilyl
      ethers which are formed via a [1,3] carbon to oxygen silyl group shift. Further
      transformations of the benzannulation products are described providing efficient
      access to ortho-benzoquinones and benzofuran, benzoxepine, and benzoxocine ring
      systems.

PMID- 19180174
TI  - A primer on regression methods for decoding cis-regulatory logic.

PMID- 19180175
TI  - Microblogging the ISMB: a new approach to conference reporting.

PMID- 19180176
TI  - A Review of 2008 for PLoS Computational Biology.

PMID- 19180178
TI  - Poisson-Nernst-Planck models of nonequilibrium ion electrodiffusion through a
      protegrin transmembrane pore.
AB  - Protegrin peptides are potent antimicrobial agents believed to act against a
      variety of pathogens by forming nonselective transmembrane pores in the bacterial
      cell membrane. We have employed 3D Poisson-Nernst-Planck (PNP) calculations to
      determine the steady-state ion conduction characteristics of such pores at
      applied voltages in the range of -100 to +100 mV in 0.1 M KCl bath solutions. We
      have tested a variety of pore structures extracted from molecular dynamics (MD)
      simulations based on an experimentally proposed octomeric pore structure. The
      computed single-channel conductance values were in the range of 290-680 pS.
      Better agreement with the experimental range of 40-360 pS was obtained using
      structures from the last 40 ns of the MD simulation, where conductance values
      range from 280 to 430 pS. We observed no significant variation of the conductance
      with applied voltage in any of the structures that we tested, suggesting that the
      voltage dependence observed experimentally is a result of voltage-dependent
      channel formation rather than an inherent feature of the open pore structure. We
      have found the pore to be highly selective for anions, with anionic to cationic
      current ratios (I(Cl-)/I(K+)) on the order of 10(3). This is consistent with the
      highly cationic nature of the pore but surprisingly in disagreement with the
      experimental finding of only slight anionic selectivity. We have additionally
      tested the sensitivity of our PNP model to several parameters and found the ion
      diffusion coefficients to have a significant influence on conductance
      characteristics. The best agreement with experimental data was obtained using a
      diffusion coefficient for each ion set to 10% of the bulk literature value
      everywhere inside the channel, a scaling used by several other studies employing
      PNP calculations. Overall, this work presents a useful link between previous work
      focused on the structure of protegrin pores and experimental efforts aimed at
      investigating their conductance characteristics.

PMID- 19180177
TI  - A factor graph nested effects model to identify networks from genetic
      perturbations.
AB  - Complex phenotypes such as the transformation of a normal population of cells
      into cancerous tissue result from a series of molecular triggers gone awry. We
      describe a method that searches for a genetic network consistent with expression
      changes observed under the knock-down of a set of genes that share a common role
      in the cell, such as a disease phenotype. The method extends the Nested Effects
      Model of Markowetz et al. (2005) by using a probabilistic factor graph to search
      for a network representing interactions among these silenced genes. The method
      also expands the network by attaching new genes at specific downstream points,
      providing candidates for subsequent perturbations to further characterize the
      pathway. We investigated an extension provided by the factor graph approach in
      which the model distinguishes between inhibitory and stimulatory interactions. We
      found that the extension yielded significant improvements in recovering the
      structure of simulated and Saccharomyces cerevisae networks. We applied the
      approach to discover a signaling network among genes involved in a human colon
      cancer cell invasiveness pathway. The method predicts several genes with new
      roles in the invasiveness process. We knocked down two genes identified by our
      approach and found that both knock-downs produce loss of invasive potential in a
      colon cancer cell line. Nested effects models may be a powerful tool for
      inferring regulatory connections and genes that operate in normal and disease
      related processes.

PMID- 19180179
TI  - Coordinated concentration changes of transcripts and metabolites in Saccharomyces
      cerevisiae.
AB  - Metabolite concentrations can regulate gene expression, which can in turn
      regulate metabolic activity. The extent to which functionally related transcripts
      and metabolites show similar patterns of concentration changes, however, remains
      unestablished. We measure and analyze the metabolomic and transcriptional
      responses of Saccharomyces cerevisiae to carbon and nitrogen starvation. Our
      analysis demonstrates that transcripts and metabolites show coordinated response
      dynamics. Furthermore, metabolites and gene products whose concentration profiles
      are alike tend to participate in related biological processes. To identify
      specific, functionally related genes and metabolites, we develop an approach
      based on Bayesian integration of the joint metabolomic and transcriptomic data.
      This algorithm finds interactions by evaluating transcript-metabolite
      correlations in light of the experimental context in which they occur and the
      class of metabolite involved. It effectively predicts known enzymatic and
      regulatory relationships, including a gene-metabolite interaction central to the
      glycolytic-gluconeogenetic switch. This work provides quantitative evidence that
      functionally related metabolites and transcripts show coherent patterns of
      behavior on the genome scale and lays the groundwork for building gene-metabolite
      interaction networks directly from systems-level data.

PMID- 19180180
TI  - Efficient network reconstruction from dynamical cascades identifies small-world
      topology of neuronal avalanches.
AB  - Cascading activity is commonly found in complex systems with directed
      interactions such as metabolic networks, neuronal networks, or disease spreading
      in social networks. Substantial insight into a system's organization can be
      obtained by reconstructing the underlying functional network architecture from
      the observed activity cascades. Here we focus on Bayesian approaches and reduce
      their computational demands by introducing the Iterative Bayesian (IB) and
      Posterior Weighted Averaging (PWA) methods. We introduce a special case of PWA,
      cast in nonparametric form, which we call the normalized count (NC) algorithm. NC
      efficiently reconstructs random and small-world functional network topologies and
      architectures from subcritical, critical, and supercritical cascading dynamics
      and yields significant improvements over commonly used correlation methods. With
      experimental data, NC identified a functional and structural small-world topology
      and its corresponding traffic in cortical networks with neuronal avalanche
      dynamics.

PMID- 19180181
TI  - Cohesive versus flexible evolution of functional modules in eukaryotes.
AB  - Although functionally related proteins can be reliably predicted from
      phylogenetic profiles, many functional modules do not seem to evolve cohesively
      according to case studies and systematic analyses in prokaryotes. In this study
      we quantify the extent of evolutionary cohesiveness of functional modules in
      eukaryotes and probe the biological and methodological factors influencing our
      estimates. We have collected various datasets of protein complexes and pathways
      in Saccheromyces cerevisiae. We define orthologous groups on 34 eukaryotic
      genomes and measure the extent of cohesive evolution of sets of orthologous
      groups of which members constitute a known complex or pathway. Within this
      framework it appears that most functional modules evolve flexibly rather than
      cohesively. Even after correcting for uncertain module definitions and
      potentially problematic orthologous groups, only 46% of pathways and complexes
      evolve more cohesively than random modules. This flexibility seems partly coupled
      to the nature of the functional module because biochemical pathways are generally
      more cohesively evolving than complexes.

PMID- 19180182
TI  - Precise regulation of gene expression dynamics favors complex promoter
      architectures.
AB  - Promoters process signals through recruitment of transcription factors and RNA
      polymerase, and dynamic changes in promoter activity constitute a major noise
      source in gene expression. However, it is barely understood how complex promoter
      architectures determine key features of promoter dynamics. Here, we employ
      prototypical promoters of yeast ribosomal protein genes as well as simplified
      versions thereof to analyze the relations among promoter design, complexity, and
      function. These promoters combine the action of a general regulatory factor with
      that of specific transcription factors, a common motif of many eukaryotic
      promoters. By comprehensively analyzing stationary and dynamic promoter
      properties, this model-based approach enables us to pinpoint the structural
      characteristics underlying the observed behavior. Functional tradeoffs impose
      constraints on the promoter architecture of ribosomal protein genes. We find that
      a stable scaffold in the natural design results in low transcriptional noise and
      strong co-regulation of target genes in the presence of gene silencing. This
      configuration also exhibits superior shut-off properties, and it can serve as a
      tunable switch in living cells. Model validation with independent experimental
      data suggests that the models are sufficiently realistic. When combined, our
      results offer a mechanistic explanation for why specific factors are associated
      with low protein noise in vivo. Many of these findings hold for a broad range of
      model parameters and likely apply to other eukaryotic promoters of similar
      structure.

PMID- 19180183
TI  - Prediction of protein-protein interaction sites in sequences and 3D structures by
      random forests.
AB  - Identifying interaction sites in proteins provides important clues to the
      function of a protein and is becoming increasingly relevant in topics such as
      systems biology and drug discovery. Although there are numerous papers on the
      prediction of interaction sites using information derived from structure, there
      are only a few case reports on the prediction of interaction residues based
      solely on protein sequence. Here, a sliding window approach is combined with the
      Random Forests method to predict protein interaction sites using (i) a
      combination of sequence- and structure-derived parameters and (ii) sequence
      information alone. For sequence-based prediction we achieved a precision of 84%
      with a 26% recall and an F-measure of 40%. When combined with structural
      information, the prediction performance increases to a precision of 76% and a
      recall of 38% with an F-measure of 51%. We also present an attempt to rationalize
      the sliding window size and demonstrate that a nine-residue window is the most
      suitable for predictor construction. Finally, we demonstrate the applicability of
      our prediction methods by modeling the Ras-Raf complex using predicted
      interaction sites as target binding interfaces. Our results suggest that it is
      possible to predict protein interaction sites with quite a high accuracy using
      only sequence information.

PMID- 19180184
TI  - A microhomology-mediated break-induced replication model for the origin of human
      copy number variation.
AB  - Chromosome structural changes with nonrecurrent endpoints associated with genomic
      disorders offer windows into the mechanism of origin of copy number variation
      (CNV). A recent report of nonrecurrent duplications associated with Pelizaeus
      Merzbacher disease identified three distinctive characteristics. First, the
      majority of events can be seen to be complex, showing discontinuous duplications
      mixed with deletions, inverted duplications, and triplications. Second, junctions
      at endpoints show microhomology of 2-5 base pairs (bp). Third, endpoints occur
      near pre-existing low copy repeats (LCRs). Using these observations and evidence
      from DNA repair in other organisms, we derive a model of microhomology-mediated
      break-induced replication (MMBIR) for the origin of CNV and, ultimately, of LCRs.
      We propose that breakage of replication forks in stressed cells that are
      deficient in homologous recombination induces an aberrant repair process with
      features of break-induced replication (BIR). Under these circumstances, single
      strand 3' tails from broken replication forks will anneal with microhomology on
      any single-stranded DNA nearby, priming low-processivity polymerization with
      multiple template switches generating complex rearrangements, and eventual re
      establishment of processive replication.

PMID- 19180185
TI  - Genetic evidence for single-strand lesions initiating Nbs1-dependent homologous
      recombination in diversification of Ig v in chicken B lymphocytes.
AB  - Homologous recombination (HR) is initiated by DNA double-strand breaks (DSB).
      However, it remains unclear whether single-strand lesions also initiate HR in
      genomic DNA. Chicken B lymphocytes diversify their Immunoglobulin (Ig) V genes
      through HR (Ig gene conversion) and non-templated hypermutation. Both types of Ig
      V diversification are initiated by AID-dependent abasic-site formation. Abasic
      sites stall replication, resulting in the formation of single-stranded gaps.
      These gaps can be filled by error-prone DNA polymerases, resulting in
      hypermutation. However, it is unclear whether these single-strand gaps can also
      initiate Ig gene conversion without being first converted to DSBs. The Mre11
      Rad50-Nbs1 (MRN) complex, which produces 3' single-strand overhangs, promotes the
      initiation of DSB-induced HR in yeast. We show that a DT40 line expressing only a
      truncated form of Nbs1 (Nbs1(p70)) exhibits defective HR-dependent DSB repair,
      and a significant reduction in the rate--though not the fidelity--of Ig gene
      conversion. Interestingly, this defective gene conversion was restored to wild
      type levels by overproduction of Escherichia coli SbcB, a 3' to 5' single-strand
      specific exonuclease, without affecting DSB repair. Conversely, overexpression of
      chicken Exo1 increased the efficiency of DSB-induced gene-targeting more than 10
      fold, with no effect on Ig gene conversion. These results suggest that Ig gene
      conversion may be initiated by single-strand gaps rather than by DSBs, and, like
      SbcB, the MRN complex in DT40 may convert AID-induced lesions into single-strand
      gaps suitable for triggering HR. In summary, Ig gene conversion and hypermutation
      may share a common substrate-single-stranded gaps. Genetic analysis of the two
      types of Ig V diversification in DT40 provides a unique opportunity to gain
      insight into the molecular mechanisms underlying the filling of gaps that arise
      as a consequence of replication blocks at abasic sites, by HR and error-prone
      polymerases.

PMID- 19180186
TI  - LINE retrotransposon RNA is an essential structural and functional epigenetic
      component of a core neocentromeric chromatin.
AB  - We have previously identified and characterized the phenomenon of ectopic human
      centromeres, known as neocentromeres. Human neocentromeres form epigenetically at
      euchromatic chromosomal sites and are structurally and functionally similar to
      normal human centromeres. Recent studies have indicated that neocentromere
      formation provides a major mechanism for centromere repositioning, karyotype
      evolution, and speciation. Using a marker chromosome mardel(10) containing a
      neocentromere formed at the normal chromosomal 10q25 region, we have previously
      mapped a 330-kb CENP-A-binding domain and described an increased prevalence of L1
      retrotransposons in the underlying DNA sequences of the CENP-A-binding clusters.
      Here, we investigated the potential role of the L1 retrotransposons in the
      regulation of neocentromere activity. Determination of the transcriptional
      activity of a panel of full-length L1s (FL-L1s) across a 6-Mb region spanning the
      10q25 neocentromere chromatin identified one of the FL-L1 retrotransposons,
      designated FL-L1b and residing centrally within the CENP-A-binding clusters, to
      be transcriptionally active. We demonstrated the direct incorporation of the FL
      L1b RNA transcripts into the CENP-A-associated chromatin. RNAi-mediated knockdown
      of the FL-L1b RNA transcripts led to a reduction in CENP-A binding and an
      impaired mitotic function of the 10q25 neocentromere. These results indicate that
      LINE retrotransposon RNA is a previously undescribed essential structural and
      functional component of the neocentromeric chromatin and that retrotransposable
      elements may serve as a critical epigenetic determinant in the chromatin
      remodelling events leading to neocentromere formation.

PMID- 19180187
TI  - Regulation of kainate receptor subunit mRNA by stress and corticosteroids in the
      rat hippocampus.
AB  - Kainate receptors are a class of ionotropic glutamate receptors that have a role
      in the modulation of glutamate release and synaptic plasticity in the hippocampal
      formation. Previous studies have implicated corticosteroids in the regulation of
      these receptors and recent clinical work has shown that polymorphisms in kainate
      receptor subunit genes are associated with susceptibility to major depression and
      response to anti-depressant treatment. In the present study we sought to examine
      the effects of chronic stress and corticosteroid treatments upon the expression
      of the mRNA of kainate receptor subunits GluR5-7 and KA1-2. Our results show
      that, after 7 days, adrenalectomy results in increased expression of hippocampal
      KA1, GluR6 and GluR7 mRNAs, an effect which is reversed by treatment with
      corticosterone in the case of KA1 and GluR7 and by aldosterone treatment in the
      case of GluR6. 21 days of chronic restraint stress (CRS) elevated the expression
      of the KA1 subunit, but had no effect on the expression of the other subunits.
      Similarly, 21 days of treatment with a moderate dose of corticosterone also
      increased KA1 mRNA in the dentate gyrus, whereas a high corticosterone dose has
      no effect. Our results suggest an interaction between hippocampal kainate
      receptor composition and the hypothalamic-pituitary-adrenal (HPA) axis and show a
      selective chronic stress induced modulation of the KA1 subunit in the dentate
      gyrus and CA3 that has implications for stress-induced adaptive structural
      plasticity.

PMID- 19180188
TI  - Selective transmission of R5 HIV-1 over X4 HIV-1 at the dendritic cell-T cell
      infectious synapse is determined by the T cell activation state.
AB  - Dendritic cells (DCs) are essential antigen-presenting cells for the induction of
      T cell immunity against HIV. On the other hand, due to the susceptibility of DCs
      to HIV infection, virus replication is strongly enhanced in DC-T cell interaction
      via an immunological synapse formed during the antigen presentation process. When
      HIV-1 is isolated from individuals newly infected with the mixture of R5 and X4
      variants, R5 is predominant, irrespective of the route of infection. Because the
      early massive HIV-1 replication occurs in activated T cells and such T-cell
      activation is induced by antigen presentation, we postulated that the selective
      expansion of R5 may largely occur at the level of DC-T cell interaction. Thus,
      the immunological synapse serves as an infectious synapse through which the virus
      can be disseminated in vivo. We used fluorescent recombinant X4 and R5 HIV-1
      consisting of a common HIV-1 genome structure with distinct envelopes, which
      allowed us to discriminate the HIV-1 transmitted from DCs infected with the two
      virus mixtures to antigen-specific CD4(+) T cells by flow cytometry. We clearly
      show that the selective expansion of R5 over X4 HIV-1 did occur, which was
      determined at an early entry step by the activation status of the CD4(+) T cells
      receiving virus from DCs, but not by virus entry efficiency or productivity in
      DCs. Our results imply a promising strategy for the efficient control of HIV
      infection.

PMID- 19180189
TI  - Rotavirus NSP1 inhibits NFkappaB activation by inducing proteasome-dependent
      degradation of beta-TrCP: a novel mechanism of IFN antagonism.
AB  - Mechanisms by which viruses counter innate host defense responses generally
      involve inhibition of one or more components of the interferon (IFN) system.
      Multiple steps in the induction and amplification of IFN signaling are targeted
      for inhibition by viral proteins, and many of the IFN antagonists have direct or
      indirect effects on activation of latent cytoplasmic transcription factors.
      Rotavirus nonstructural protein NSP1 blocks transcription of type I IFNalpha/beta
      by inducing proteasome-dependent degradation of IFN-regulatory factors 3 (IRF3),
      IRF5, and IRF7. In this study, we show that rotavirus NSP1 also inhibits
      activation of NFkappaB and does so by a novel mechanism. Proteasome-mediated
      degradation of inhibitor of kappaB (IkappaBalpha) is required for NFkappaB
      activation. Phosphorylated IkappaBalpha is a substrate for polyubiquitination by
      a multisubunit E3 ubiquitin ligase complex, Skp1/Cul1/F-box, in which the F-box
      substrate recognition protein is beta-transducin repeat containing protein (beta
      TrCP). The data presented show that phosphorylated IkappaBalpha is stable in
      rotavirus-infected cells because infection induces proteasome-dependent
      degradation of beta-TrCP. NSP1 expressed in isolation in transiently transfected
      cells is sufficient to induce this effect. Targeted degradation of an F-box
      protein of an E3 ligase complex with a prominent role in modulation of innate
      immune signaling and cell proliferation pathways is a unique mechanism of IFN
      antagonism and defines a second strategy of immune evasion used by rotaviruses.

PMID- 19180190
TI  - Estimation of transmission parameters of H5N1 avian influenza virus in chickens.
AB  - Despite considerable research efforts, little is yet known about key
      epidemiological parameters of H5N1 highly pathogenic influenza viruses in their
      avian hosts. Here we show how these parameters can be estimated using a limited
      number of birds in experimental transmission studies. Our quantitative estimates,
      based on Bayesian methods of inference, reveal that (i) the period of latency of
      H5N1 influenza virus in unvaccinated chickens is short (mean: 0.24 days; 95%
      credible interval: 0.099-0.48 days); (ii) the infectious period of H5N1 virus in
      unvaccinated chickens is approximately 2 days (mean: 2.1 days; 95%CI: 1.8-2.3
      days); (iii) the reproduction number of H5N1 virus in unvaccinated chickens need
      not be high (mean: 1.6; 95%CI: 0.90-2.5), although the virus is expected to
      spread rapidly because it has a short generation interval in unvaccinated
      chickens (mean: 1.3 days; 95%CI: 1.0-1.5 days); and (iv) vaccination with
      genetically and antigenically distant H5N2 vaccines can effectively halt
      transmission. Simulations based on the estimated parameters indicate that herd
      immunity may be obtained if at least 80% of chickens in a flock are vaccinated.
      We discuss the implications for the control of H5N1 avian influenza virus in
      areas where it is endemic.

PMID- 19180191
TI  - Short telomeres initiate telomere recombination in primary and tumor cells.
AB  - Human tumors that lack telomerase maintain telomeres by alternative lengthening
      mechanisms. Tumors can also form in telomerase-deficient mice; however, the
      genetic mechanism responsible for tumor growth without telomerase is unknown. In
      yeast, several different recombination pathways maintain telomeres in the absence
      of telomerase-some result in telomere maintenance with minimal effects on
      telomere length. To examine non-telomerase mechanisms for telomere maintenance in
      mammalian cells, we used primary cells and lymphomas from telomerase-deficient
      mice (mTR-/- and Emumyc+mTR-/-) and CAST/EiJ mouse embryonic fibroblast cells.
      These cells were analyzed using pq-ratio analysis, telomere length distribution
      outliers, CO-FISH, Q-FISH, and multicolor FISH to detect subtelomeric
      recombination. Telomere length was maintained during long-term growth in vivo and
      in vitro. Long telomeres, characteristic of human ALT cells, were not observed in
      either late passage or mTR-/- tumor cells; instead, we observed only minimal
      changes in telomere length. Telomere length variation and subtelomeric
      recombination were frequent in cells with short telomeres, indicating that length
      maintenance is due to telomeric recombination. We also detected telomere length
      changes in primary mTR-/- cells that had short telomeres. Using mouse mTR+/- and
      human hTERT+/- primary cells with short telomeres, we found frequent length
      changes indicative of recombination. We conclude that telomere maintenance by non
      telomerase mechanisms, including recombination, occurs in primary cells and is
      initiated by short telomeres, even in the presence of telomerase. Most
      intriguing, our data indicate that some non-telomerase telomere maintenance
      mechanisms occur without a significant increase in telomere length.

PMID- 19180192
TI  - Learning a prior on regulatory potential from eQTL data.
AB  - Genome-wide RNA expression data provide a detailed view of an organism's
      biological state; hence, a dataset measuring expression variation between
      genetically diverse individuals (eQTL data) may provide important insights into
      the genetics of complex traits. However, with data from a relatively small number
      of individuals, it is difficult to distinguish true causal polymorphisms from the
      large number of possibilities. The problem is particularly challenging in
      populations with significant linkage disequilibrium, where traits are often
      linked to large chromosomal regions containing many genes. Here, we present a
      novel method, Lirnet, that automatically learns a regulatory potential for each
      sequence polymorphism, estimating how likely it is to have a significant effect
      on gene expression. This regulatory potential is defined in terms of "regulatory
      features"-including the function of the gene and the conservation, type, and
      position of genetic polymorphisms-that are available for any organism. The extent
      to which the different features influence the regulatory potential is learned
      automatically, making Lirnet readily applicable to different datasets, organisms,
      and feature sets. We apply Lirnet both to the human HapMap eQTL dataset and to a
      yeast eQTL dataset and provide statistical and biological results demonstrating
      that Lirnet produces significantly better regulatory programs than other recent
      approaches. We demonstrate in the yeast data that Lirnet can correctly suggest a
      specific causal sequence variation within a large, linked chromosomal region. In
      one example, Lirnet uncovered a novel, experimentally validated connection
      between Puf3-a sequence-specific RNA binding protein-and P-bodies-cytoplasmic
      structures that regulate translation and RNA stability-as well as the particular
      causative polymorphism, a SNP in Mkt1, that induces the variation in the pathway.

PMID- 19180194
TI  - Systemic correlates of angiographic coronary artery disease.
AB  - Coronary angiography allows a direct evaluation of coronary anatomy. The aim of
      the present investigation was to search for correlations between the magnitude of
      coronary artery disease, as assessed by angiography, and a number of systemic
      parameters. A group of 116 patients (80 male, 36 female) with coronary heart
      disease diagnosed by angiography, aged 62.0+/-10.5 years, was the subject of an
      observational study. Correlation and linear regression analysis using coronary
      artery disease burden (CADB - sum of the percentage of the luminal stenosis
      encountered in all the lesions of the coronary arterial trees) as dependent
      variable, and age, sex, plasma calcium, phosphorus, magnesium, glucose, HDL
      cholesterol, LDL cholesterol, triglycerides, uric acid, estimated glomerular
      filtration rate and body mass index as independent variables, were carried out.
      Significant correlation values versus CADB were seen with age (r 0.19, p 0.04),
      uric acid (r 0.18, p 0.048) and fasting plasma glucose (r 0.33, p<0.001). Linear
      regression analysis, yielding a global significance level of 0.002, showed a
      significant value for glucose (p 0.018) and for sex (0.008). In conclusion, among
      several systemic parameters studied, plasma glucose was found to be correlated to
      coronary artery atherosclerosis lesions.

PMID- 19180193
TI  - DETORQUEO, QUIRKY, and ZERZAUST represent novel components involved in organ
      development mediated by the receptor-like kinase STRUBBELIG in Arabidopsis
      thaliana.
AB  - Intercellular signaling plays an important role in controlling cellular behavior
      in apical meristems and developing organs in plants. One prominent example in
      Arabidopsis is the regulation of floral organ shape, ovule integument
      morphogenesis, the cell division plane, and root hair patterning by the leucine
      rich repeat receptor-like kinase STRUBBELIG (SUB). Interestingly, kinase activity
      of SUB is not essential for its in vivo function, indicating that SUB may be an
      atypical or inactive receptor-like kinase. Since little is known about signaling
      by atypical receptor-like kinases, we used forward genetics to identify genes
      that potentially function in SUB-dependent processes and found recessive
      mutations in three genes that result in a sub-like phenotype. Plants with a
      defect in DETORQEO (DOQ), QUIRKY (QKY), and ZERZAUST (ZET) show corresponding
      defects in outer integument development, floral organ shape, and stem twisting.
      The mutants also show sub-like cellular defects in the floral meristem and in
      root hair patterning. Thus, SUB, DOQ, QKY, and ZET define the STRUBBELIG-LIKE
      MUTANT (SLM) class of genes. Molecular cloning of QKY identified a putative
      transmembrane protein carrying four C(2) domains, suggesting that QKY may
      function in membrane trafficking in a Ca(2+)-dependent fashion. Morphological
      analysis of single and all pair-wise double-mutant combinations indicated that
      SLM genes have overlapping, but also distinct, functions in plant organogenesis.
      This notion was supported by a systematic comparison of whole-genome transcript
      profiles during floral development, which molecularly defined common and distinct
      sets of affected processes in slm mutants. Further analysis indicated that many
      SLM-responsive genes have functions in cell wall biology, hormone signaling, and
      various stress responses. Taken together, our data suggest that DOQ, QKY, and ZET
      contribute to SUB-dependent organogenesis and shed light on the mechanisms, which
      are dependent on signaling through the atypical receptor-like kinase SUB.

PMID- 19180195
TI  - Network adaptation improves temporal representation of naturalistic stimuli in
      Drosophila eye: II mechanisms.
AB  - Retinal networks must adapt constantly to best present the ever changing visual
      world to the brain. Here we test the hypothesis that adaptation is a result of
      different mechanisms at several synaptic connections within the network. In a
      companion paper (Part I), we showed that adaptation in the photoreceptors (R1-R6)
      and large monopolar cells (LMC) of the Drosophila eye improves sensitivity to
      under-represented signals in seconds by enhancing both the amplitude and
      frequency distribution of LMCs' voltage responses to repeated naturalistic
      contrast series. In this paper, we show that such adaptation needs both the light
      mediated conductance and feedback-mediated synaptic conductance. A faulty
      feedforward pathway in histamine receptor mutant flies speeds up the LMC output,
      mimicking extreme light adaptation. A faulty feedback pathway from L2 LMCs to
      photoreceptors slows down the LMC output, mimicking dark adaptation. These
      results underline the importance of network adaptation for efficient coding, and
      as a mechanism for selectively regulating the size and speed of signals in
      neurons. We suggest that concert action of many different mechanisms and neural
      connections are responsible for adaptation to visual stimuli. Further, our
      results demonstrate the need for detailed circuit reconstructions like that of
      the Drosophila lamina, to understand how networks process information.

PMID- 19180196
TI  - Network adaptation improves temporal representation of naturalistic stimuli in
      Drosophila eye: I dynamics.
AB  - Because of the limited processing capacity of eyes, retinal networks must adapt
      constantly to best present the ever changing visual world to the brain. However,
      we still know little about how adaptation in retinal networks shapes neural
      encoding of changing information. To study this question, we recorded voltage
      responses from photoreceptors (R1-R6) and their output neurons (LMCs) in the
      Drosophila eye to repeated patterns of contrast values, collected from natural
      scenes. By analyzing the continuous photoreceptor-to-LMC transformations of these
      graded-potential neurons, we show that the efficiency of coding is dynamically
      improved by adaptation. In particular, adaptation enhances both the frequency and
      amplitude distribution of LMC output by improving sensitivity to under
      represented signals within seconds. Moreover, the signal-to-noise ratio of LMC
      output increases in the same time scale. We suggest that these coding properties
      can be used to study network adaptation using the genetic tools in Drosophila, as
      shown in a companion paper (Part II).

PMID- 19180197
TI  - Exercise improves cognitive responses to psychological stress through enhancement
      of epigenetic mechanisms and gene expression in the dentate gyrus.
AB  - BACKGROUND: We have shown previously that exercise benefits stress resistance and
      stress coping capabilities. Furthermore, we reported recently that epigenetic
      changes related to gene transcription are involved in memory formation of
      stressful events. In view of the enhanced coping capabilities in exercised
      subjects we investigated epigenetic, gene expression and behavioral changes in 4
      weeks voluntarily exercised rats. METHODOLOGY/PRINCIPAL FINDINGS: Exercised and
      control rats coped differently when exposed to a novel environment. Whereas the
      control rats explored the new cage for the complete 30-min period, exercised
      animals only did so during the first 15 min after which they returned to sleeping
      or resting behavior. Both groups of animals showed similar behavioral responses
      in the initial forced swim session. When re-tested 24 h later however the
      exercised rats showed significantly more immobility behavior and less struggling
      and swimming. If rats were killed at 2 h after novelty or the initial swim test,
      i.e. at the peak of histone H3 phospho-acetylation and c-Fos induction, then the
      exercised rats showed a significantly higher number of dentate granule neurons
      expressing the histone modifications and immediate-early gene induction.
      CONCLUSIONS/SIGNIFICANCE: Thus, irrespective of the behavioral response in the
      novel cage or initial forced swim session, the impact of the event at the dentate
      gyrus level was greater in exercised rats than in control animals. Furthermore,
      in view of our concept that the neuronal response in the dentate gyrus after
      forced swimming is involved in memory formation of the stressful event, the
      observations in exercised rats of enhanced neuronal responses as well as higher
      immobility responses in the re-test are consistent with the reportedly improved
      cognitive performance in these animals. Thus, improved stress coping in exercised
      subjects seems to involve enhanced cognitive capabilities possibly resulting from
      distinct epigenetic mechanisms in dentate gyrus neurons.

PMID- 19180198
TI  - Staphylococcus aureus bacteraemia in a tropical setting: patient outcome and
      impact of antibiotic resistance.
AB  - BACKGROUND: Most information on invasive Staphylococcus aureus infections comes
      from temperate countries. There are considerable knowledge gaps in epidemiology,
      treatment, drug resistance and outcome of invasive S. aureus infection in the
      tropics. METHODS: A prospective, observational study of S. aureus bacteraemia was
      conducted in a 1000-bed regional hospital in northeast Thailand over 1 year.
      Detailed clinical data were collected and final outcomes determined at 12 weeks,
      and correlated with antimicrobial susceptibility profiles of infecting isolates.
      PRINCIPAL FINDINGS: Ninety-eight patients with S. aureus bacteraemia were
      recruited. The range of clinical manifestations was similar to that reported from
      temperate countries. The prevalence of endocarditis was 14%. The disease burden
      was highest at both extremes of age, whilst mortality increased with age. The all
      cause mortality rate was 52%, with a mortality attributable to S. aureus of 44%.
      Methicillin-resistant S. aureus (MRSA) was responsible for 28% of infections, all
      of which were healthcare-associated. Mortality rates for MRSA and methicillin
      susceptible S. aureus (MSSA) were 67% (18/27) and 46% (33/71), respectively (p =
      0.11). MRSA isolates were multidrug resistant. Only vancomycin or fusidic acid
      would be suitable as empirical treatment options for suspected MRSA infection.
      CONCLUSIONS: S. aureus is a significant pathogen in northeast Thailand, with
      comparable clinical manifestations and a similar endocarditis prevalence but
      higher mortality than industrialised countries. S. aureus bacteraemia is
      frequently associated with exposure to healthcare settings with MRSA causing a
      considerable burden of disease. Further studies are required to define setting
      specific strategies to reduce mortality from S. aureus bacteraemia, prevent MRSA
      transmission, and to define the burden of S. aureus disease and emergence of drug
      resistance throughout the developing world.

PMID- 19180199
TI  - Effects of colchicine on localization of alkaline phosphatase in McA-RH 7777 rat
      hepatoma cells.
AB  - We investigated the changes caused by microtubule disruption in cell contact
      induced translocation of alkaline phosphatase (ALP) from the Golgi area to the
      plasma membrane in McA-RH 7777 cells. When the cells were treated with
      colchicine, the tubular structure of microtubules in the cytoplasm was lost.
      Colchicine treatment also resulted in the appearance of numerous dots containing
      mannosidase II (man II) throughout the cytoplasm. Moreover, ALP was distributed
      in small dots throughout the cytoplasm, as well as in all regions of the plasma
      membrane, although it was most concentrated at sites of intercellular contact. On
      the other hand, when the cells were incubated in basal medium after colchicine
      treatment, large spots containing ALP reappeared in the perinuclear cytoplasm
      more quickly than the accumulation of small dots containing man II. These
      findings suggest that colchicine causes disassembly of the Golgi complex into
      fragments, which scatter throughout the cytoplasm, but that it does not interfere
      with translocation of ALP to the plasma membrane. Furthermore, cytoplasmic ALP
      may be localized at sites other than the Golgi complex.

PMID- 19180200
TI  - Expression pattern of cyclooxygenase-2 in normal rat epidermis and pilosebaceous
      unit during hair cycle.
AB  - As an important member of the cyclooxygenase isoenzymes, cyclooxygenase-2 (COX-2)
      mainly catalyzes the first two steps in prostanoid synthesis. In mammalian
      animals, although COX-2 was thought to be rarely expressed in most normal tissues
      and was usually upregulated in a variety of epithelial tumors and inflammatory
      reactions, recently it was reported that COX-2 could localize in the epidermis as
      well as the pilosebaceous unit of the normal human and mouse skin. Until now, the
      function of COX-2 in normal skin has remained unknown. To investigate the
      possible roles of COX-2 in normal skin by RT-PCR and immunochemistry, we studied
      the expression pattern of COX-2 in hair cycle of the normal rat skin. The
      expression of COX-2 mRNA was detected in normal rat skin sample and was related
      to the hair follicle cycle. When the hair cycle entered catagen and telogen, COX
      2 mRNA transcription in skin increased significantly. Furthermore, the location
      of COX-2 immunoreactivity showed that COX-2 protein is mainly concentrated in the
      epidermis and pilosebaceous unit. In the stratified epidermis, the strong COX-2
      protein expression was detected in the suprabasal layers of epidermis in anagen
      and declined in catagen and telogen. In hair follicle, COX-2 protein was
      obviously expressed in the outer root sheath of the anagen hair follicle, and was
      barely detectable in catagen as well as telogen. In the sebaceous gland, the COX
      2 protein expression became more intense in catagen and telogen, with an increase
      in sebaceous gland size. Our results suggested that COX-2 was not specific to
      some abnormal tissues and was indeed involved in the normal physiology of rat
      skin, such as the differentiation of epidermis, the morphogenesis of the hair
      follicle, the transformation of hair cycle stages, and the lipid production of
      the sebaceous gland.

PMID- 19180202
TI  - Synaptophysin expression in rat retina following acute high intraocular pressure.
AB  - In response to injury, synapse alteration may occur earlier than the changes in
      the cell body of neurons. Although retinal ganglion cell death and thinning of
      the inner part of retina were found after acute high intraocular pressure (HIOP),
      the structural and functional changes of synapses in the retina remain unknown.
      In the present study, we investigated the protein and mRNA expression of
      synaptophysin (SYN), an important molecule closely related to synaptic
      activities, synaptogenesis and synaptic plasticity. In addition, we also studied
      the ultrastructural changes of the retinal synapses. We found that (1)
      synaptophysin was upregulated transiently at both protein and mRNA level
      following HIOP; (2) broadened distribution of synaptophysin protein was present
      within the outer nuclear layer at the early stage following HIOP; (3) in the
      outer nuclear layer bouton-like vesicle-containing structures were observed by
      electron microscopy. This data suggested that, besides degeneration, synapses in
      rat retina may undergo regenerative events following HIOP.

PMID- 19180201
TI  - Expression of histo-blood group A type 1, 2 and 3 antigens in normal skin and
      extramammary Paget's disease.
AB  - The distribution of histo-blood group A type 1, 2 and 3 antigens was investigated
      using immunohistochemistry in normal human skin and extramammary Paget's disease
      (EMPD). We used monoclonal antibodies (mAbs) Bioclone-A (BA) and AR-1, which
      react with histo-blood group A type 1/2, and type 3 antigens, respectively. We
      found that A type 1, 2 and 3 antigens were expressed in the upper layer of the
      epidermis. We also found that the duct cells of the eccrine glands expressed A
      type 1/2 antigens and A type 3 antigens regardless of secretor status. The dark
      cells of the eccrine glands expressed A type 1, 2 and 3 antigens from A blood
      group secretors, but not from non-secretors. Apocrine glands, hair follicles and
      sebaceous glands did not express these antigens. Since these antigens were
      localized in the eccrine glands, we examined the possibility of a skin tumor
      marker. Interestingly, 7 out of 16 extramammary Paget's disease cases were
      immunopositive for these antigens. Six cases were accompanied by dermal invasion.
      Five cases without dermal invasion were immunonegative against these antigens.
      These results suggest that the expression of histo-blood group A antigens in EMPD
      are associated with a poor histopathological prognosis.

PMID- 19180203
TI  - The Efficacy of Amodiaquine plus Artesunate Combination in Ghana.

PMID- 19180204
TI  - Efficacy of amodiaquine/artesunate combination therapy for uncomplicated malaria
      in children under five years in ghana.
AB  - BACKGROUND: In 2005, following several years of declining efficacy of
      chloroquine, the Ministry of Health recommended the use of Amodiaquine/Artesunate
      combination therapy for the treatment of uncomplicated malaria. A system of
      continuous monitoring of therapeutic responses has been established in 10
      district hospitals across the country. The data gathered will enable National
      Malaria Control Programme (NMCP) to respond to changes in the efficacy of the new
      treatment in a timely manner. OBJECTIVES: To determine the 28 day therapeutic
      efficacy of Amodiaquine/Artesunate (AQ/AS) combination treatment in children with
      uncomplicated malaria in Ghana. METHODS: Children aged 6 - 59 months attending
      clinic with signs/symptoms of uncomplicated malaria at 9 district hospitals (3 in
      each of the 3 eco-epidemiological zones of the country) were eligible for
      enrolment. Enrolled children were followed up after treatment for a total of 28
      days to record the clinical and parasitological resolution of their malaria
      episode as well as any adverse drug reactions. RESULTS: Treatment resulted in
      rapid and complete cure in almost all the children; 99.3% 14 days after treatment
      and 93.0%, 28 days after treatment. The majority of treatment failures on D28
      were seen in the 3 sites located in the forest zones (Sunyani, Bekwai and
      Begoro). There was no case of Early Treatment Failure at both D14 and D28
      assessments. Adverse events (AE's) were minimal, less than 4%, with the most
      common complaint being vomiting. CONCLUSION: AQ/AS combination for uncomplicated
      malaria is efficacious and safe in children less than 5 years.

PMID- 19180205
TI  - Control perceptions and control appraisal: relation to measures of subjective
      well-being.
AB  - OBJECTIVES: To investigate the relationship between control variables and
      measures of subjective well-being. The primary question asked was "who is happy
      and well, and why?" DESIGN: A questionnaire survey and the data was analyzed by
      examining bivariate relationships between variables of interest. PARTICIPANTS:
      Two hundred and fifty six (256) adults within the age range of 18-88 years. They
      were mainly undergraduate psychology students from South-Eastern part of the
      United States and solicited in a manner consistent with the Institutional Review
      Board of the Florida State University. Elderly persons from community groups
      (e.g. churches, social organizations) were solicited through their appropriate
      leaders and announcements. RESULTS: The mean age of the participants was 32
      years. Findings indicated significant relationship between control measures,
      indices of wellbeing, and individual's satisfaction with the quality of their
      lives. Significant correlations were between 0.177 and 0.469 at the 0.01 level (2
      tailed). Having control in the areas of social support, self-acceptance, positive
      relationships, purpose in life, and personal growth were judged important.
      CONCLUSION: The findings of this study suggest that essential 'ingredients' for
      psychological and subjective well-being include enjoyment of good health, some
      financial stability, meaningful ties with others, a sense of purpose and
      direction in life, ability to manage complex life demands, a healthy self
      acceptance and commitment to personal development. Implications for clinical
      utility and future research are discussed.

PMID- 19180206
TI  - Emergency contraception: knowledge and perception of female undergraduates in the
      niger delta of Nigeria.
AB  - OBJECTIVE: To evaluate the knowledge of, and perception of female undergraduates
      in the Niger Delta of Nigeria towards Emergency Contraception. METHODS: Anonymous
      self administered questionnaires were applied to randomly selected non-medical
      female undergraduates of the University of Port Harcourt in May 2005. RESULTS:
      Six hundred questionnaires were retrieved out of 610 distributed. The respondents
      were between 17-30 years. Those reported to have ever had sex were 85.3%; most of
      whom (98.4%) have previously used some forms of contraception. About 50.7% of 600
      respondents were aware of emergency contraception; amongst which reports of
      friends/peers as the source of knowledge ranked highest (33.55%). About 88.2% of
      those that are aware of Emergency Contraception knew the correct timing. More
      than half (57.9%) did not know correct dosage of the available post-coital pill.
      While half (50.7%) of those having knowledge of postcoital pills agree to the
      efficacy; only a third (35.53%) agreed to have actually used it. CONCLUSION: The
      awareness and use of Emergency Contraception amongst female undergraduates in
      Niger Delta region of Nigeria is low. Prompt education of this group of students
      in Emergency Contraception should be encouraged with emphasis on available
      methods and correct timing of use.

PMID- 19180207
TI  - Cervical human papillomavirus infection in accra, ghana.
AB  - BACKGROUND: This study was aimed at estimating the human papillomavirus (HPV)
      prevalence and its determinants among a sample of Ghanaian women. DESIGN: Cross
      sectional observational study. SETTING: Gynaecology outpatient clinic of the
      Korle-Bu Teaching Hospital, Accra, Ghana; the largest tertiary care gynaecology
      outpatient clinic in Ghana. PARTICIPANTS: Convenient sample of 75 consenting
      women visiting the clinic. METHODS: Information was obtained through personal
      interviews using structured questionnaire, Pap smears obtained, and laboratory
      testing of cervical exfoliated cells was performed. HPV DNA was detected using a
      GP5+/6+ polymerase chain reaction assay. These data were analyzed using both
      univariate and bivariate techniques. RESULTS: The mean age of participants was
      33.3 years (standard deviation, 9.2) and the percentage of lifetime monogamy was
      21.3%. The crude HPV DNA prevalence was 10.7%. Unlike most populations studied so
      far, HPV prevalence was high not only among young women, but also in middle and
      old age. Independent HPV determinants were being illiterate (prevalence odds
      ratio [POR], 13.9; 95% confidence interval [95%CI], 1.9-100) and reporting more
      than three lifetime sexual partners (POR, 4.6; 95% CI, 1.0-22.2). CONCLUSIONS:
      The study indicates a high crude prevalence of HPV in a largely polygamous
      Ghanaian population with a high crude prevalence in older age groups, which may
      be a distinctive feature of polygamous populations where HPV transmission
      continues into middle age and cervical cancer incidence is very high.

PMID- 19180208
TI  - Analgesic activity of crude aqueous extract of the root bark of zanthoxylum
      xanthoxyloides.
AB  - OBJECTIVE: The analgesic activity of crude aqueous extract of the root bark of
      Zanthoxylum xanthozyloides was studied in mice and rats with the view to
      verifying the claim in folklore medicine that the extract has analgesic activity.
      METHOD: The extract was obtained by Soxhlet extraction and rotatory evaporation,
      followed by freeze-drying. Groups of rats and mice were, respectively, assigned
      randomly to treatment groups. The animals received three different treatments
      orally: 0.9% saline (control), the extract (400mg/kg and 800mg/kg for mice;
      1000mg/kg and 2000mg/kg for rats) and indomethacin (5mg/kg and 10mg/kg for mice;
      10mg/kg and 20mg/kg for rats). Each group of animals was rotated through the
      entire treatment groups such that each animal served as control as well as
      received all the treatments. The hot-plate and paw-pressure methods were used to
      study pain perception in the treated animals. Analysis of variance was used as
      the statistical test. RESULTS: In both methods, the extract and indomethacin
      caused dose-dependent elevation in pain threshold. At the peak of activity,
      400mg/kg and 800mg/kg extract caused 74% and 95% increase in the reaction time
      respectively whilst 5mg/kg and 10mg/kg indomethacin gave 97% and 116% increment
      respectively. Similarly, 1000mg/kg and 2000mg/kg extract caused 65% and 84%
      increase in pain threshold whilst 10mg/kg and 20mg/kg indomethacin caused 95% and
      113% increment respectively. CONCLUSION: It was concluded that the extract
      induced analgesia, probably, by inhibiting prostaglandin production, just as did
      indomethacin.

PMID- 19180209
TI  - In vivo inhibition of prostaglandin e(2) production by crude aqueous extract of
      the root bark of zanthoxylum xanthoxyloides.
AB  - BACKGROUND: Crude aqueous extract of the root bark of Zanthoxylum xanthoxyloides
      is used in folklore medicine for its anti-inflammatory activity. Although it
      shares the analgesic and anti-inflammatory property of non-steroidal anti
      inflammatory drugs (NSAIDs), its mechanism of action has not been well
      elucidated. OBJECTIVE: To ascertain whether the extract decreases carrageenin
      induced increase in plasma prostaglandin E(2) (PGE(2)) concentration with the
      view to shed light on the mechanism of action. METHODS: The extract was obtained
      by Soxhlet extraction and rotatory evaporation, followed by freeze-drying. Forty
      Wistar rats (150g - 200g) were assigned to 8 groups of 5 rats each. The rats were
      given four different treatments orally: 0.9% saline (two groups of control); two
      groups received indomethacin, 20mg/kg and 40mg/kg respectively; another two
      groups received the extract, 2000mg/kg and 4000mg/kg respectively; and the
      remaining two groups, 50mg/kg and 100mg/kg nimesulide respectively. Inflammation
      was induced with carrageenin in one of the two groups of control. Enzyme-linked
      immunospecific assay was used to measure plasma PGE(2) concentration in the
      control and treated groups of rats. Analysis of variance was used as the
      statistical test. Differences in means at p<0.05 were considered significant.
      RESULTS: Carrageenin increased plasma PGE(2) concentration which was reduced by
      the extract, indomethacin and nimesulide. High dose extract and indomethacin
      reduced plasma PGE(2) concentration to a comparable extent which was much greater
      than that of the reduction caused by nimesulide. CONCLUSION: It was concluded
      that the extract might act by non-selective inhibition of cyclooxygenase 1 and 2
      to decrease plasma PGE(2) concentration.

PMID- 19180210
TI  - Social pathology of cleft palate in the african: mathematical precision of pitch
      gaps in tribal tonal linguistics.

PMID- 19180211
TI  - Rudimentary horn pregnancy: pre-rupture diagnosis and management.
AB  - Rudimentary horn pregnancy is a rare obstetric entity and the diagnosis and
      management may pose some problems especially in a low-resource center. We report
      our experience in diagnosing and managing a case of fetal death in a rudimentary
      horn.

PMID- 19180212
TI  - 2008 Physical Activity Guidelines for Americans: an opportunity for athletic
      trainers.

PMID- 19180213
TI  - Concentric and eccentric torque of the hip musculature in individuals with and
      without patellofemoral pain.
AB  - CONTEXT: Individuals suffering from patellofemoral pain have previously been
      reported to have decreased isometric strength of the hip musculature; however, no
      researchers have investigated concentric and eccentric torque of the hip
      musculature in individuals with patellofemoral pain. OBJECTIVE: To compare
      concentric and eccentric torque of the hip musculature in individuals with and
      without patellofemoral pain. DESIGN: Case control. SETTING: Research laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Twenty participants with patellofemoral pain (age
      = 26.8 +/- 4.5 years, height = 171.8 +/- 8.4 cm, mass = 72.4 +/- 16.8 kg) and 20
      control participants (age = 25.6 +/- 2.8 years, height = 169.5 +/- 8.9 cm, mass =
      70.0 +/- 16.9 kg) were tested. Volunteers with patellofemoral pain met the
      following criteria: knee pain greater than or equal to 3 cm on a 10-cm visual
      analog scale, insidious onset of symptoms not related to trauma, pain with
      palpation of the patellar facets, and knee pain during 2 of the following
      activities: stair climbing, jumping or running, squatting, kneeling, or prolonged
      sitting. Control participants were excluded if they had a prior history of
      patellofemoral pain, knee surgery in the past 2 years, or current lower extremity
      injury that limited participation in physical activity. INTERVENTION(S):
      Concentric and eccentric torque of the hip musculature was measured on an
      isokinetic dynamometer. All volunteers performed 5 repetitions of each strength
      test. Separate multivariate analyses of variance were performed to compare
      concentric and eccentric torque of the hip extensors, abductors, and external
      rotators between groups. MAIN OUTCOME MEASURE(S): Average and peak concentric and
      eccentric torque of the hip extensors, abductors, and external rotators. Torque
      measures were normalized to the participant's body weight multiplied by height.
      RESULTS: The patellofemoral pain group was weaker than the control group for peak
      eccentric hip abduction torque (F(1,38) = 6.630, P = .014), and average
      concentric (F(1,38) = 4.156, P = .048) and eccentric (F(1,38) = 4.963, P = .032)
      hip external rotation torque. CONCLUSIONS: The patellofemoral pain group
      displayed weakness in eccentric hip abduction and hip external rotation, which
      may allow for increased hip adduction and internal rotation during functional
      movements.

PMID- 19180214
TI  - Thigh muscle activity, knee motion, and impact force during side-step pivoting in
      agility-trained female basketball players.
AB  - CONTEXT: Improving neuromuscular control of hamstrings muscles might have
      implications for decreasing anterior cruciate ligament injuries in females.
      OBJECTIVE: To examine the effects of a 6-week agility training program on
      quadriceps and hamstrings muscle activation, knee flexion angles, and peak
      vertical ground reaction force. DESIGN: Prospective, randomized clinical research
      trial. SETTING: Sports medicine research laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Thirty female intramural basketball players with no history of knee
      injury (age = 21.07 +/- 2.82 years, height = 171.27 +/- 4.66 cm, mass = 66.36 +/-
      7.41 kg). INTERVENTION(S): Participants were assigned to an agility training
      group or a control group that did not participate in agility training.
      Participants in the agility training group trained 4 times per week for 6 weeks.
      MAIN OUTCOME MEASURE(S): We used surface electromyography to assess muscle
      activation for the rectus femoris, vastus medialis oblique, medial hamstrings,
      and lateral hamstrings for 50 milliseconds before initial ground contact and
      while the foot was in contact with the ground during a side-step pivot maneuver.
      Knee flexion angles (at initial ground contact, maximum knee flexion, knee
      flexion displacement) and peak vertical ground reaction force also were assessed
      during this maneuver. RESULTS: Participants in the training group increased
      medial hamstrings activation during ground contact after the 6-week agility
      training program. Both groups decreased their vastus medialis oblique muscle
      activation during ground contact. Knee flexion angles and peak vertical ground
      reaction force did not change for either group. CONCLUSIONS: Agility training
      improved medial hamstrings activity in female intramural basketball players
      during a side-step pivot maneuver. Agility training that improves hamstrings
      activity might have implications for reducing anterior cruciate ligament sprain
      injury associated with side-step pivots.

PMID- 19180215
TI  - Dynamic valgus alignment and functional strength in males and females during
      maturation.
AB  - CONTEXT: Sex differences in dynamic measures have been established in physically
      mature populations. Gaining information on maturation's effect on dynamic
      performance measures implicated in injury risk may enable us to better design
      injury prevention programs. OBJECTIVE: To examine sex differences in dynamic
      valgus alignment and triple-hop distance measures across maturational stages in
      males and females. A secondary purpose was to determine if a field test of
      strength and power predicts dynamic valgus alignment. DESIGN: Cross-sectional
      study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: 157 young athletes
      (78 females, 79 males) aged 9 to 18 years. INTERVENTION(S): Subjects performed
      drop-jump landings and single-leg triple-hop tests as part of a broader injury
      screening. MAIN OUTCOME MEASURE(S): Maturational status was ascertained from self
      report questionnaires and grouped according to Tanner stages 1 and 2 (MatGrp1), 3
      and 4 (MatGrp2), and 5 (MatGrp3). Frontal-plane knee valgus displacement, which
      served as a measure of dynamic valgus alignment, and single-leg triple-hop
      distance were assessed. RESULTS: Males demonstrated less dynamic valgus alignment
      during drop jumps in the latter maturational stages (MatGrp1 = 13.1 degrees +/-
      8.7 degrees , MatGrp2 = 9.0 degrees +/- 6.2 degrees , MatGrp3 = 9.2 degrees +/-
      9.4 degrees ), whereas females increased dynamic valgus alignment throughout
      maturation (MatGrp1 = 11.5 degrees +/- 6.9 degrees , MatGrp2 = 12.8 degrees +/-
      8.8 degrees , MatGrp3 = 15.5 degrees +/- 8.7 degrees ). Thus, in the more mature
      groups, males had less dynamic valgus alignment than females. Both males (MatGrp1
      = 393.5 +/- 63.7 cm, MatGrp2 = 491.8 +/- 95.1 cm, MatGrp3 = 559.3 +/- 76.3 cm)
      and females (MatGrp1 = 360.3 +/- 37.1 cm, MatGrp2 = 380.1 +/- 44.3 cm, MatGrp3 =
      440.0 +/- 66.2 cm) increased triple-hop distance, but males increased more.
      Within each subgroup of MatGrp and sex, triple-hop distance had no predictive
      ability for dynamic malalignment. CONCLUSIONS: When dynamic valgus alignment and
      strength were assessed, sex and maturational status displayed an interaction.
      However, functional strength did not predict degree of dynamic valgus alignment.

PMID- 19180216
TI  - The relationships among sagittal-plane lower extremity moments: implications for
      landing strategy in anterior cruciate ligament injury prevention.
AB  - CONTEXT: Excessive quadriceps contraction with insufficient hamstrings muscle
      cocontraction has been shown to be a possible contributing factor for noncontact
      anterior cruciate ligament (ACL) injuries. Assessing the relationships among
      lower extremity internal moments may provide some insight into avoiding muscle
      contraction patterns that increase ACL injury risk. OBJECTIVE: To examine the
      relationships of knee-extensor moment with ankle plantar-flexor and hip-extensor
      moments and to examine the relationship between knee moment and center of
      pressure as a measure of neuromuscular response to center-of-mass position.
      DESIGN: Cross-sectional study. SETTING: Applied Neuromechanics Research
      Laboratory. PATIENTS OR OTHER PARTICIPANTS: Eighteen healthy, recreationally
      active women (age = 22.3 +/- 2.8 years, height = 162.5 +/- 8.1 cm, mass = 57.8 +/
      9.3 kg). INTERVENTION(S): Participants performed a single-leg landing from a 45
      cm box onto a force plate. Kinetic and kinematic data were collected. MAIN
      OUTCOME MEASURE(S): Pearson product moment correlation coefficients were
      calculated among the net peak knee-extensor moment (KEMpk), sagittal-plane ankle
      (AM) and hip (HM) net internal moments, and anterior-posterior center of pressure
      relative to foot center of mass at KEMpk (COP). RESULTS: Lower KEMpk related to
      both greater AM (r = -0.942, P < .001) and HM (r = -0.657, P = .003). We also
      found that more anterior displacement of COP was related to greater AM (r = 
      0.750, P < .001) and lower KEMpk (r = 0.618, P = .006). CONCLUSIONS: Our results
      suggest that participants who lean the whole body forward during landing may
      produce more plantar-flexor moment and less knee-extensor moment, possibly
      increasing hip-extensor moment and decreasing knee-extensor moment production.
      These results suggest that leaning forward may be a technique to decrease
      quadriceps contraction demand while increasing hamstrings cocontraction demand
      during a single-leg landing.

PMID- 19180218
TI  - Application of generalizability theory in estimating the reliability of ankle
      complex laxity measurement.
AB  - CONTEXT: Generalizability theory is an appropriate method for determining the
      reliability of measurements obtained across more than a single facet. In the
      clinical and research settings, ankle-complex laxity assessment may be performed
      using different examiners and multiple trials. OBJECTIVE: To determine the
      reliability of ankle-complex laxity measurements across different examiners and
      multiple trials using generalizability theory. DESIGN: Correlational study.
      SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Forty male university
      students without a history of ankle injury. MAIN OUTCOME MEASURE(S): Measures of
      right ankle-complex anteroposterior and inversion-eversion laxity were obtained
      by 2 examiners. Each examiner performed 2 anteroposterior trials, followed by 2
      inversion-eversion trials for each ankle at 0 degrees of ankle flexion. Using
      generalizability theory, we performed G study and D study analyses. RESULTS: More
      measurement error was found for facets associated with examiner than with trial
      for both anteroposterior and inversion-eversion laxity. Inversion-eversion
      measurement was more reliable than anteroposterior laxity measurement. Although 1
      examiner and 1 trial had acceptable reliability (G coefficient >/= .848),
      increasing the number of examiners increased reliability to a greater extent than
      did increasing the number of trials. CONCLUSIONS: Within the range of examiner
      and trial facets studied, any combination of examiners or trials (or both) above
      1 can change ankle laxity measurement reliability from acceptable (1 examiner, 1
      trial) to highly reliable (3 examiners, 3 trials). Individuals may respond to
      examiners and their procedural nuances differently; thus, standardized procedures
      are important.

PMID- 19180217
TI  - Explosive strength imbalances in professional basketball players.
AB  - CONTEXT: Despite the high rate of lower limb injuries in basketball players,
      studies of the dominant-limb effect in elite athletes often neglect injury
      history. OBJECTIVE: To determine lower limb explosive-strength asymmetries in
      professional basketball players compared with junior basketball players and
      control participants. DESIGN: Cohort study. SETTING: Academic medical
      institution. PATIENTS OR OTHER PARTICIPANTS: 15 professional basketball players,
      10 junior basketball players, and 20 healthy men. MAIN OUTCOME MEASURE(S): We
      performed an isokinetic examination to evaluate the knee extensor (Ext) and
      flexor (Fl) concentric peak torque at 60 degrees .s(-1) and 240 degrees .s(-1)
      and (Fl only) eccentric peak torque at 30 degrees .s(-1) and 120 degrees .s(-1).
      Functional evaluation included countermovement jump, countermovement jump with
      arms, 10-m sprint, single-leg drop jump, and single-leg, 10-second continuous
      jumping. Variables were compared among groups using analysis of variance or a
      generalized linear mixed model for bilateral variables. RESULTS: The 2 groups of
      basketball players demonstrated better isokinetic and functional performances
      than the control group did. No differences in functional or relative isokinetic
      variables were noted between professional and junior basketball players.
      Professional players with a history of knee injury failed to reach normal knee
      extensor strength at 60 degrees .s(-1). Knee Ext (60 degrees .s(-1)) and Fl
      (eccentric 120 degrees .s(-1)) torque values as well as 10-second continuous
      jumping scores were higher in those professional players without a history of
      knee injury than those with such a history. Compared with the group without a
      history of knee injury, the group with a history of knee injury maintained leg
      asymmetry ratios greater than 10% for almost all isokinetic variables and more
      than 15% for unilateral functional variables. CONCLUSIONS: The relative
      isokinetic and functional performances of professional basketball players were
      similar to those of junior players, with no dominant-side effect. A history of
      knee injury in the professional athlete, however, was reflected in bilateral
      isokinetic and functional asymmetries and should be considered in future studies
      of explosive strength.

PMID- 19180219
TI  - Pregame urine specific gravity and fluid intake by National Basketball
      Association players during competition.
AB  - CONTEXT: Urine specific gravity (USG) has been used to estimate hydration status
      in athletes on the field, with increasing levels of hypohydration indicated by
      higher USG measurements (eg, greater than 1.020). Whether initial hydration
      status based on a urine measure is related to subsequent drinking response during
      exercise or athletic competition is unclear. OBJECTIVE: To determine the
      relationship between pregame USG and the volume of fluid consumed by players in a
      professional basketball game. DESIGN: Cross-sectional study. SETTING: Basketball
      players were monitored during Summer League competition. PATIENTS OR OTHER
      PARTICIPANTS: Players (n = 29) from 5 teams of the National Basketball
      Association agreed to participate. MAIN OUTCOME MEASURE(S): Pregame USG was
      measured for each player on 2 occasions. Athletes were given ad libitum access to
      fluid during each game and were unaware of the purpose of the study. Volume of
      fluid intake was measured for each player. To assess sweat loss, athletes were
      weighed in shorts before and after each game. RESULTS: Sweat loss ranged from 1.0
      to 4.6 L, with a mean sweat loss of 2.2 +/- 0.8 L. Fluid intake ranged from 0.1
      to 2.9 L, with a mean fluid intake of 1.0 +/- 0.6 L. Pregame USG was greater than
      1.020 in 52% of the urine samples collected and was not correlated with fluid
      volume consumed during either of the games (r = 0.15, P = .48, and r = 0.15, P =
      .52, respectively). CONCLUSIONS: Approximately half of the players began the
      games in a hypohydrated state, as indicated by USG. Fluid intake during the game
      did not compensate for poor hydration status before competition. Furthermore,
      sweat losses in these players during games were substantial (greater than 2 L in
      approximately 20 minutes of playing time). Therefore, both pregame and during
      game hydration strategies, such as beverage availability and player education,
      should be emphasized.

PMID- 19180220
TI  - Personal and environmental characteristics predicting burnout among certified
      athletic trainers at National Collegiate Athletic Association institutions.
AB  - CONTEXT: Recent research in the health care professions has shown that specific
      personal and environmental characteristics can predict burnout, which is a
      negative coping strategy related to stressful situations. Burnout has been shown
      to result in physiologic (eg, headaches, difficulty sleeping, poor appetite),
      psychological (eg, increased negative self-talk, depression, difficulty in
      interpersonal relationships), and behavioral (eg, diminished care, increased
      absenteeism, attrition) symptoms. OBJECTIVE: To examine the relationship between
      selected personal and environmental characteristics and burnout among certified
      athletic trainers (ATs). DESIGN: Cross-sectional survey. SETTING: A demographic
      survey that was designed for this study and the Maslach Burnout Inventory-Human
      Services Survey. PATIENTS OR OTHER PARTICIPANTS: A total of 206 ATs employed at
      National Collegiate Athletic Association (NCAA) institutions as clinical ATs
      volunteered. MAIN OUTCOME MEASURE(S): We assessed personal and environmental
      characteristics of ATs with the demographic survey and measured burnout using the
      Maslach Burnout Inventory-Human Services Survey. Multiple regression analyses
      were performed to examine relationships between specific personal and
      environmental characteristics and each of the 3 subscales of burnout (emotional
      exhaustion, depersonalization, personal accomplishment). RESULTS: Most ATs we
      surveyed experienced low to average levels of burnout. Personal characteristics
      predicted 45.5% of the variance in emotional exhaustion (P < .001), 21.5% of the
      variance in depersonalization (P < .001), and 24.8% of the variance in personal
      accomplishment (P < .001). Environmental characteristics predicted 16.7% of the
      variance in emotional exhaustion (P = .005), 14.4% of the variance in
      depersonalization (P = .024), and 10.4% of the variance in personal
      accomplishment (P = .209). Stress level and coaches' pressure to medically clear
      athletes predicted ratings on all 3 subscales of burnout. CONCLUSIONS: Our
      findings were similar to those of other studies of burnout among NCAA Division I
      ATs, coaches, and coach-teachers. The results also support the Cognitive
      Affective Model of Athletic Burnout proposed by Smith. Finally, these results
      indicate new areas of concentration for burnout research and professional
      practice.

PMID- 19180221
TI  - Recently certified athletic trainers' undergraduate educational preparation in
      psychosocial intervention and referral.
AB  - CONTEXT: "Psychosocial Intervention and Referral" is one of the 12 content areas
      established by the National Athletic Trainers' Association Education Council and
      is required to be taught in athletic training education programs (ATEPs). The
      perceived preparation of athletic trainers (ATs) in this content area has not
      been evaluated. OBJECTIVE: To explore the preparation level of recently certified
      ATs within the content area of "Psychosocial Intervention and Referral." DESIGN:
      Qualitative design involving semistructured, in-depth, focus group interviews.
      SETTING: Interviews were conducted at 2 National Collegiate Athletic Association
      Division I institutions in 2 regions of the United States. PATIENTS OR OTHER
      PARTICIPANTS: A total of 11 recently certified ATs who met predetermined criteria
      were recruited. The ATs represented a range of undergraduate ATEPs and current
      employment settings. DATA COLLECTION AND ANALYSIS: Focus group interviews were
      transcribed verbatim and analyzed deductively. Peer debriefing and member checks
      were used to ensure trustworthiness. RESULTS: The ATEPs are doing an adequate job
      of preparing ATs for many common communication and interpersonal issues, but ATs
      report being underprepared to deal with athlete-related issues in the areas of
      motivation and adherence, counseling and social support, mental skills training,
      and psychosocial referral. CONCLUSIONS: Limitations of undergraduate ATEPs
      regarding preparation of athletic training students within the "Psychosocial
      Intervention and Referral" content area were identified, with the goal of
      improving athletic training education. The more we know about the issues that
      entry-level ATs face, the more effectively we can structure athletic training
      education.

PMID- 19180222
TI  - Shoulder injuries among United States high school athletes during the 2005-2006
      and 2006-2007 school years.
AB  - CONTEXT: The shoulder is one of the most commonly injured body sites among
      athletes. Little previous research describes shoulder injury patterns in high
      school athletes. OBJECTIVE: To describe and compare shoulder injury rates and
      patterns among high school athletes in 9 sports (football, soccer, basketball,
      baseball, and wrestling for boys and soccer, volleyball, basketball, and softball
      for girls). DESIGN: Prospective injury surveillance study. SETTING: Injury data
      were collected from 100 nationally representative US high schools via High School
      Reporting Information Online. PATIENTS OR OTHER PARTICIPANTS: Athletes from
      participating high schools injured while involved in a school-sanctioned practice
      or competition in 1 of the above sports during the 2005-2006 and 2006-2007 school
      years. MAIN OUTCOME MEASURE(S): Shoulder injury rates, diagnoses, severity, and
      mechanisms. RESULTS: During the 2005-2006 and 2006-2007 school years, athletes in
      this study sustained 805 shoulder injuries during 3 550 141 athlete-exposures
      (AEs), for an injury rate of 2.27 shoulder injuries per 10 000 AEs. This
      corresponds to an estimated 232 258 shoulder injuries occurring nationwide during
      this time. Shoulder injuries were more likely to occur during competition than
      practice (rate ratio = 3.01, 95% confidence interval = 2.62, 3.46). Shoulder
      injury rates per 10 000 AEs were highest in football (5.09), wrestling (4.34),
      and baseball (1.90). Common shoulder injury diagnoses included sprains/strains
      (39.6%), dislocations/separations (23.7%), contusions (11.5%), and fractures
      (6.6%). Although 44.8% of athletes sustaining a shoulder injury returned to play
      in less than 1 week, 22.9% were out of play for more than 3 weeks, and 6.2% of
      shoulder injuries required surgery. Common mechanisms of shoulder injury included
      player-to-player contact (57.6%) and contact with the playing surface (22.8%).
      CONCLUSIONS: High school shoulder injury rates and patterns varied by sport.
      Continued surveillance is warranted to understand trends and patterns over time
      and to develop and evaluate evidence-based preventive interventions.

PMID- 19180223
TI  - Acute whole-body cooling for exercise-induced hyperthermia: a systematic review.
AB  - OBJECTIVE: To assess existing original research addressing the efficiency of
      whole-body cooling modalities in the treatment of exertional hyperthermia. DATA
      SOURCES: During April 2007, we searched MEDLINE, EMBASE, Scopus, SportDiscus,
      CINAHL, and Cochrane Reviews databases as well as ProQuest for theses and
      dissertations to identify research studies evaluating whole-body cooling
      treatments without limits. Key words were cooling, cryotherapy, water immersion,
      cold-water immersion, ice-water immersion, icing, fanning, bath, baths, cooling
      modality, heat illness, heat illnesses, exertional heatstroke, exertional heat
      stroke, heat exhaustion, hyperthermia, hyperthermic, hyperpyrexia, exercise,
      exertion, running, football, military, runners, marathoner, physical activity,
      marathoning, soccer, and tennis. DATA SYNTHESIS: Two independent reviewers graded
      each study on the Physiotherapy Evidence Database (PEDro) scale. Seven of 89
      research articles met all inclusion criteria and a minimum score of 4 out of 10
      on the PEDro scale. CONCLUSIONS: After an extensive and critical review of the
      available research on whole-body cooling for the treatment of exertional
      hyperthermia, we concluded that ice-water immersion provides the most efficient
      cooling. Further research comparing whole-body cooling modalities is needed to
      identify other acceptable means. When ice-water immersion is not possible,
      continual dousing with water combined with fanning the patient is an alternative
      method until more advanced cooling means can be used. Until future investigators
      identify other acceptable whole-body cooling modalities for exercise-induced
      hyperthermia, ice-water immersion and cold-water immersion are the methods proven
      to have the fastest cooling rates.

PMID- 19180224
TI  - Unique treatment regimen for effort thrombosis in the nondominant extremity of an
      overhead athlete: a case report.
AB  - OBJECTIVE: To advise athletic trainers on the potential for effort thrombosis to
      occur in nonthrowing athletes and to underscore the importance of early
      recognition and treatment. BACKGROUND: An 18-year-old offensive lineman presented
      with a 1-day history of diffuse shoulder pain with no specific history of injury;
      swelling and erythema involved the entire left upper extremity. He was
      immediately referred to the team physician, who suspected deep vein thrombosis
      and sent the athlete to an imaging center. Duplex ultrasound was obtained on the
      day of presentation, and he was admitted to the hospital that evening.
      DIFFERENTIAL DIAGNOSIS: Deep vein thrombosis, thoracic outlet syndrome, shoulder
      tendinitis. TREATMENT: Anticoagulation with heparin was administered at the
      hospital, and he was sent home the next day on subcutaneous enoxaparin sodium,
      followed by a 5-mg daily dose of oral warfarin sodium. Oral anticoagulants were
      continued for a total of 4 weeks. The athlete began upper body lifting and was
      released 5 weeks postinjury to gradually return to football without restrictions.
      UNIQUENESS: Effort thrombosis is typically seen in the dominant arm of athletes,
      and the current treatment protocol calls for thrombolysis or surgical
      intervention. This athlete, whose position required repeated elevation of his
      arms in forward flexion, sustained the injury in his nondominant arm, was treated
      with anticoagulation only, and had a full return to football. At 18-month follow
      up, he had no recurrence of symptoms. CONCLUSIONS: Early recognition and
      treatment of athletes with effort thrombosis is paramount to a successful
      clinical outcome and prompt return to play.

PMID- 19180225
TI  - Rhabdomyolysis of the deltoid muscle in a bodybuilder using anabolic-androgenic
      steroids: a case report.
AB  - OBJECTIVE: Rhabdomyolysis (breakdown of skeletal muscle tissue) may be caused by
      mechanical, physical, chemical, or biological factors. We present the unique case
      of a bodybuilder who developed localized rhabdomyolysis of the deltoid muscle
      after injection of steroids into the shoulder region. BACKGROUND: A 39-year-old
      amateur bodybuilder presented to the emergency department with excruciating pain
      and inability to move his right shoulder after injecting stanozolol, an anabolic
      androgenic steroid (AAS), into his right deltoid muscle on the same day. On
      physical examination, the right deltoid muscle was swollen and tense and the
      surrounding skin red, tender, and warm. He had no fluctuation or systemic fever
      and no sensory or motor deficit. His distal pulsations were distinct. Laboratory
      test results suggested massive rhabdomyolysis. The major magnetic resonance
      imaging finding was diffuse hyperintensity signals on T2-weighted images of the
      deltoid muscle, which was consistent with edema. DIFFERENTIAL DIAGNOSIS:
      Polymyositis and dermatomyositis, mild injury, infectious myositis without
      phlegmon or abscess formation, radiation therapy, subacute denervation,
      compartment syndrome, early myositis ossificans, rhabdomyolysis, and sickle cell
      crisis. TREATMENT: The patient was treated with intravenous fluid replacement and
      sodium bicarbonate to alkalinize the urine. Four days after admission, his pain
      had decreased, he had regained range of motion, and his renal function remained
      unaffected. UNIQUENESS: Anabolic-androgenic steroid use is associated with
      various side effects that are generally systemic and dose related. We could not
      find reports of localized side effects of AAS use, as this case presented,
      elsewhere in the English-language literature. CONCLUSIONS: "Doping" among amateur
      athletes occurs frequently. It can cause acute and chronic health problems, most
      of which are systemic. This is the first description of localized rhabdomyolysis
      in the area of an AAS injection.

PMID- 19180227
TI  - PRINCIPAL COMPONENTS FOR NON-LOCAL MEANS IMAGE DENOISING.
AB  - This paper presents an image denoising algorithm that uses principal component
      analysis (PCA) in conjunction with the non-local means image denoising. Image
      neighborhood vectors used in the non-local means algorithm are first projected
      onto a lower-dimensional subspace using PCA. Consequently, neighborhood
      similarity weights for denoising are computed using distances in this subspace
      rather than the full space. This modification to the non-local means algorithm
      results in improved accuracy and computational performance. We present an
      analysis of the proposed method's accuracy as a function of the dimensionality of
      the projection subspace and demonstrate that denoising accuracy peaks at a
      relatively low number of dimensions.

PMID- 19180226
TI  - Longitudinal assessment of noncontact anterior cruciate ligament injury risk
      factors during maturation in a female athlete: a case report.
AB  - OBJECTIVE: To present a unique case of a young pubertal female athlete who was
      prospectively monitored for previously identified anterior cruciate ligament
      (ACL) injury risk factors for 3 years before sustaining an ACL injury.
      BACKGROUND: In prospective studies, previous investigators have examined cross
      sectional measures of anatomic, hormonal, and biomechanical risk factors for ACL
      injury in young female athletes. In this report, we offer a longitudinal example
      of measured risk factors as the participant matured. DIFFERENTIAL DIAGNOSIS:
      Partial or complete tear of the ACL. MEASUREMENTS: The participant was identified
      from a cohort monitored from 2002 until 2007. No injury prevention training or
      intervention was included during this time in the study cohort. FINDINGS: The
      injury occurred in the year after the third assessment during the athlete's club
      basketball season. Knee examination, magnetic resonance imaging findings, and
      arthroscopic evaluation confirmed a complete ACL rupture. The athlete was early
      pubertal in year 1 of the study and pubertal during the next 2 years; menarche
      occurred at age 12 years. At the time of injury, she was 14.25 years old and
      postpubertal, with closing femoral and tibial physes. For each of the 3 years
      before injury, she demonstrated incremental increases in height, body mass index,
      and anterior knee laxity. She also displayed decreased hip abduction and knee
      flexor strength, concomitant with increased knee abduction loads, after each year
      of growth. CONCLUSIONS: During puberty, the participant increased body mass and
      height of the center of mass without matching increases in hip and knee strength.
      The lack of strength and neuromuscular adaptation to match the increased demands
      of her pubertal stature may underlie the increased knee abduction loads measured
      at each annual visit and may have predisposed her to increased risk of ACL
      injury.

PMID- 19180228
TI  - FINE-GRAINED PITCH ACCENT AND BOUNDARY TONE LABELING WITH PARAMETRIC F0 FEATURES.
AB  - Motivated by linguistic theories of prosodic categoricity, symbolic
      representations of prosody have recently attracted the attention of speech
      technologists. Categorical representations such as ToBI not only bear linguistic
      relevance, but also have the advantage that they can be easily modeled and
      integrated within applications. Since manual labeling of these categories is time
      consuming and expensive, there has been significant interest in automatic prosody
      labeling. This paper presents a fine-grained ToBI-style prosody labeling system
      that makes use of features derived from RFC and TILT parameterization of F0
      together with a n-gram prosodic language model for 4-way pitch accent labeling
      and 2-way boundary tone labeling. For this task, our system achieves pitch accent
      labeling accuracy of 56.4% and boundary tone labeling accuracy of 67.7% on the
      Boston University Radio News Corpus.

PMID- 19180229
TI  - Metabolic consequences and vulnerability to diet-induced obesity in male mice
      under chronic social stress.
AB  - Social and psychological factors interact with genetic predisposition and dietary
      habit in determining obesity. However, relatively few pre-clinical studies
      address the role of psychosocial factors in metabolic disorders. Previous studies
      from our laboratory demonstrated in male mice: 1) opposite status-dependent
      effect on body weight gain under chronic psychosocial stress; 2) a reduction in
      body weight in individually housed (Ind) male mice. In the present study these
      observations were extended to provide a comprehensive characterization of the
      metabolic consequences of chronic psychosocial stress and individual housing in
      adult CD-1 male mice. Results confirmed that in mice fed standard diet, dominant
      (Dom) and Ind had a negative energy balance while subordinate (Sub) had a
      positive energy balance. Locomotor activity was depressed in Sub and enhanced in
      Dom. Hyperphagia emerged for Dom and Sub and hypophagia for Ind. Dom also showed
      a consistent decrease of visceral fat pads weight as well as increased
      norepinephrine concentration and smaller adipocytes diameter in the perigonadal
      fat pad. On the contrary, under high fat diet Sub and, surprisingly, Ind showed
      higher while Dom showed lower vulnerability to obesity associated with
      hyperphagia. In conclusion, we demonstrated that social status under chronic
      stress and individual housing deeply affect mice metabolic functions in
      different, sometime opposite, directions. Food intake, the hedonic response to
      palatable food as well as the locomotor activity and the sympathetic activation
      within the adipose fat pads all represent causal factors explaining the different
      metabolic alterations observed. Overall this study demonstrates that pre-clinical
      animal models offer a suitable tool for the investigation of the metabolic
      consequences of chronic stress exposure and associated psychopathologies.

PMID- 19180230
TI  - Multiple independent genetic factors at NOS1AP modulate the QT interval in a
      multi-ethnic population.
AB  - Extremes of electrocardiographic QT interval are associated with increased risk
      for sudden cardiac death (SCD); thus, identification and characterization of
      genetic variants that modulate QT interval may elucidate the underlying etiology
      of SCD. Previous studies have revealed an association between a common genetic
      variant in NOS1AP and QT interval in populations of European ancestry, but this
      finding has not been extended to other ethnic populations. We sought to
      characterize the effects of NOS1AP genetic variants on QT interval in the multi
      ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most
      strongly associated with QT interval in previous samples of European ancestry,
      rs16847548, was the most strongly associated in White (P = 0.005) and Black (P =
      3.6 x 10(-5)) participants, with the same direction of effect in Hispanics (P =
      0.17), and further showed a significant SNP x sex-interaction (P = 0.03). A
      second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT
      interval in Blacks (P = 0.01), with qualitatively similar results in Whites and
      Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn
      from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular
      Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P =
      7.63 x 10(-8)), as well as the sex-interaction with rs16847548 (P = 8.68 x 10(
      6)). These data extend the association of genetic variants in NOS1AP with QT
      interval to a Black population, with similar trends, though not statistically
      significant at P<0.05, in Hispanics. In addition, we identify a strong sex
      interaction and the presence of a second independent site within NOS1AP
      associated with the QT interval. These results highlight the consistent and
      complex role of NOS1AP genetic variants in modulating QT interval.

PMID- 19180231
TI  - PECAM-independent thioglycollate peritonitis is associated with a locus on murine
      chromosome 2.
AB  - BACKGROUND: Previous studies have demonstrated that knockout or inhibition of
      Platelet/Endothelial Cell Adhesion Molecule (PECAM, CD31) in a number of murine
      strains results in impaired inflammatory responses, but that no such phenotype is
      seen in the C57BL/6 (B6) murine background. METHODOLOGY/PRINCIPAL FINDINGS: We
      have undertaken a quantitative trait locus (QTL) mapping effort between FVB/n
      (FVB) and B6 mice deficient for PECAM to identify the gene or genes responsible
      for this unique feature of B6 mice. We have identified a locus on murine
      chromosome 2 at approximately 35.8 Mb that is strongly associated (LOD score =
      9.0) with inflammatory responses in the absence of PECAM.
      CONCLUSIONS/SIGNIFICANCE: These data potentiate further study of the diapedesis
      machinery, as well as potential identification of new components of this
      machinery. As such, this study is an important step to better understanding the
      processes of inflammation.

PMID- 19180232
TI  - CCL3L Copy number variation and the co-evolution of primate and viral genomes.

PMID- 19180234
TI  - Polar localization of virulence-related Esx-1 secretion in mycobacteria.
AB  - The Esx-1 (type VII) secretion system is critical for virulence of both
      Mycobacterium tuberculosis and Mycobacterium marinum, and is highly conserved
      between the two species. Despite its importance, there has been no direct
      visualization of Esx-1 secretion until now. In M. marinum, we show that secretion
      of Mh3864, a novel Esx-1 substrate that remains partially cell wall-associated
      after translocation, occurred in polar regions, indicating that Esx-1 secretion
      takes place in these regions. Analysis of Esx-1 secretion in infected host cells
      suggested that Esx-1 activity is similarly localized in vivo. A core component of
      the Esx-1 apparatus, Mh3870, also localized to bacterial poles, showing a
      preference for new poles with active cell wall peptidoglycan (PGN) synthesis.
      This work demonstrates that the Esx-1 secretion machine localizes to, and is
      active at, the bacterial poles. Thus, virulence-related protein secretion is
      localized in mycobacteria, suggesting new potential therapeutic targets, which
      are urgently needed.

PMID- 19180233
TI  - Reduced neutrophil count in people of African descent is due to a regulatory
      variant in the Duffy antigen receptor for chemokines gene.
AB  - Persistently low white blood cell count (WBC) and neutrophil count is a well
      described phenomenon in persons of African ancestry, whose etiology remains
      unknown. We recently used admixture mapping to identify an approximately 1
      megabase region on chromosome 1, where ancestry status (African or European)
      almost entirely accounted for the difference in WBC between African Americans and
      European Americans. To identify the specific genetic change responsible for this
      association, we analyzed genotype and phenotype data from 6,005 African Americans
      from the Jackson Heart Study (JHS), the Health, Aging and Body Composition
      (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We
      demonstrate that the causal variant must be at least 91% different in frequency
      between West Africans and European Americans. An excellent candidate is the Duffy
      Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only
      polymorphism in the region known to be so differentiated in frequency and is
      already known to protect against Plasmodium vivax malaria. We confirm that
      rs2814778 is predictive of WBC and neutrophil count in African Americans above
      beyond the previously described admixture association (P = 3.8 x 10(-5)),
      establishing a novel phenotype for this genetic variant.

PMID- 19180235
TI  - The sicker sex.

PMID- 19180236
TI  - Diploids in the Cryptococcus neoformans serotype A population homozygous for the
      alpha mating type originate via unisexual mating.
AB  - The ubiquitous environmental human pathogen Cryptococcus neoformans is
      traditionally considered a haploid fungus with a bipolar mating system. In
      nature, the alpha mating type is overwhelmingly predominant over a. How genetic
      diversity is generated and maintained by this heterothallic fungus in a largely
      unisexual alpha population is unclear. Recently it was discovered that C.
      neoformans can undergo same-sex mating under laboratory conditions generating
      both diploid intermediates and haploid recombinant progeny. Same-sex mating
      (alpha-alpha) also occurs in nature as evidenced by the existence of natural
      diploid alphaADalpha hybrids that arose by fusion between two alpha cells of
      different serotypes (A and D). How significantly this novel sexual style
      contributes to genetic diversity of the Cryptococcus population was unknown. In
      this study, approximately 500 natural C. neoformans isolates were tested for
      ploidy and close to 8% were found to be diploid by fluorescence flow cytometry
      analysis. The majority of these diploids were serotype A isolates with two copies
      of the alpha MAT locus allele. Among those, several are intra-varietal
      allodiploid hybrids produced by fusion of two genetically distinct alpha cells
      through same-sex mating. The majority, however, are autodiploids that harbor two
      seemingly identical copies of the genome and arose via either endoreplication or
      clonal mating. The diploids identified were isolated from different geographic
      locations and varied genotypically and phenotypically, indicating independent non
      clonal origins. The present study demonstrates that unisexual mating produces
      diploid isolates of C. neoformans in nature, giving rise to populations of
      hybrids and mixed ploidy. Our findings underscore the importance of same-sex
      mating in shaping the current population structure of this important human
      pathogenic fungus, with implications for mechanisms of selfing and inbreeding in
      other microbial pathogens.

PMID- 19180238
TI  - Conceptual challenges of a tentative model of stress-induced depression.

PMID- 19180237
TI  - Stress and depression: preclinical research and clinical implications.

PMID- 19180239
TI  - Expression of the axonal membrane glycoprotein M6a is regulated by chronic
      stress.
AB  - It has been repeatedly shown that chronic stress changes dendrites, spines and
      modulates expression of synaptic molecules. These effects all may impair
      information transfer between neurons. The present study shows that chronic stress
      also regulates expression of M6a, a glycoprotein which is localised in axonal
      membranes. We have previously demonstrated that M6a is a component of
      glutamatergic axons. The present data reveal that it is the splice variant M6a
      Ib, not M6a-Ia, which is strongly expressed in the brain. Chronic stress in male
      rats (3 weeks daily restraint) has regional effects: quantitative in situ
      hybridization demonstrated that M6a-Ib mRNA in dentate gyrus granule neurons and
      in CA3 pyramidal neurons is downregulated, whereas M6a-Ib mRNA in the medial
      prefrontal cortex is upregulated by chronic stress. This is the first study
      showing that expression of an axonal membrane molecule is differentially affected
      by stress in a region-dependent manner. Therefore, one may speculate that
      diminished expression of the glycoprotein in the hippocampus leads to altered
      output in the corresponding cortical projection areas. Enhanced M6a-Ib expression
      in the medial prefrontal cortex (in areas prelimbic and infralimbic cortex) might
      be interpreted as a compensatory mechanism in response to changes in axonal
      projections from the hippocampus. Our findings provide evidence that in addition
      to alterations in dendrites and spines chronic stress also changes the integrity
      of axons and may thus impair information transfer even between distant brain
      regions.

PMID- 19180240
TI  - Towards predictive computational models of oncolytic virus therapy: basis for
      experimental validation and model selection.
AB  - Oncolytic viruses are viruses that specifically infect cancer cells and kill
      them, while leaving healthy cells largely intact. Their ability to spread through
      the tumor makes them an attractive therapy approach. While promising results have
      been observed in clinical trials, solid success remains elusive since we lack
      understanding of the basic principles that govern the dynamical interactions
      between the virus and the cancer. In this respect, computational models can help
      experimental research at optimizing treatment regimes. Although preliminary
      mathematical work has been performed, this suffers from the fact that individual
      models are largely arbitrary and based on biologically uncertain assumptions.
      Here, we present a general framework to study the dynamics of oncolytic viruses
      that is independent of uncertain and arbitrary mathematical formulations. We find
      two categories of dynamics, depending on the assumptions about spatial
      constraints that govern that spread of the virus from cell to cell. If infected
      cells are mixed among uninfected cells, there exists a viral replication rate
      threshold beyond which tumor control is the only outcome. On the other hand, if
      infected cells are clustered together (e.g. in a solid tumor), then we observe
      more complicated dynamics in which the outcome of therapy might go either way,
      depending on the initial number of cells and viruses. We fit our models to
      previously published experimental data and discuss aspects of model validation,
      selection, and experimental design. This framework can be used as a basis for
      model selection and validation in the context of future, more detailed
      experimental studies. It can further serve as the basis for future, more complex
      models that take into account other clinically relevant factors such as immune
      responses.

PMID- 19180241
TI  - Local inflammation induces complement crosstalk which amplifies the antimicrobial
      response.
AB  - By eliciting inflammatory responses, the human immunosurveillance system notably
      combats invading pathogens, during which acute phase proteins (CRP and cytokines)
      are elevated markedly. However, the Pseudomonas aeruginosa is a persistent
      opportunistic pathogen prevalent at the site of local inflammation, and its
      acquisition of multiple antibiotic-resistance factors poses grave challenges to
      patient healthcare management. Using blood samples from infected patients, we
      demonstrate that P. aeruginosa is effectively killed in the plasma under defined
      local infection-inflammation condition, where slight acidosis and reduced calcium
      levels (pH 6.5, 2 mM calcium) typically prevail. We showed that this powerful
      antimicrobial activity is provoked by crosstalk between two plasma proteins;
      CRPratioL-ficolin interaction led to communication between the complement
      classical and lectin pathways from which two amplification events emerged. Assays
      for C4 deposition, phagocytosis, and protein competition consistently proved the
      functional significance of the amplification pathways in boosting complement
      mediated antimicrobial activity. The infection-inflammation condition induced a
      100-fold increase in CRPratioL-ficolin interaction in a pH- and calcium-sensitive
      manner. We conclude that the infection-induced local inflammatory conditions
      trigger a strong interaction between CRPratioL-ficolin, eliciting complement
      amplification pathways which are autonomous and which co-exist with and reinforce
      the classical and lectin pathways. Our findings provide new insights into the
      host immune response to P. aeruginosa infection under pathological conditions and
      the potential development of new therapeutic strategies against bacterial
      infection.

PMID- 19180242
TI  - Opposite effects of early maternal deprivation on neurogenesis in male versus
      female rats.
AB  - BACKGROUND: Major depression is more prevalent in women than in men. The
      underlying neurobiological mechanisms are not well understood, but recent data
      shows that hippocampal volume reductions in depressed women occur only when
      depression is preceded by an early life stressor. This underlines the potential
      importance of early life stress, at least in women, for the vulnerability to
      develop depression. Perinatal stress exposure in rodents affects critical periods
      of brain development that persistently alter structural, emotional and
      neuroendocrine parameters in adult offspring. Moreover, stress inhibits adult
      hippocampal neurogenesis, a form of structural plasticity that has been
      implicated a.o. in antidepressant action and is highly abundant early
      postnatally. We here tested the hypothesis that early life stress differentially
      affects hippocampal structural plasticity in female versus male offspring.
      PRINCIPAL FINDINGS: We show that 24 h of maternal deprivation (MD) at PND3
      affects hippocampal structural plasticity at PND21 in a sex-dependent manner.
      Neurogenesis was significantly increased in male but decreased in female
      offspring after MD. Since no other structural changes were found in granule cell
      layer volume, newborn cell survival or proliferation rate, astrocyte number or
      gliogenesis, this indicates that MD elicits specific changes in subsets of
      differentiating cells and differentially affects immature neurons. The MD induced
      sex-specific effects on neurogenesis cannot be explained by differences in
      maternal care. CONCLUSIONS: Our data shows that early environment has a critical
      influence on establishing sex differences in neural plasticity and supports the
      concept that the setpoint for neurogenesis may be determined during perinatal
      life. It is tempting to speculate that a reduced level of neurogenesis, secondary
      to early stress exposure, may contribute to maladaptation of the HPA axis and
      possibly to the increased vulnerability of women to stress-related disorders.

PMID- 19180245
TI  - Agreement between Parent and Adolescent Reports of Adolescent Substance Use.
AB  - This study examined the correspondence between parent and adolescent reports of
      the adolescent's substance use in a population of parents concerned about, and
      experiencing problems resulting from, their teen's substance use. Seventy-five
      parents and their adolescent (76% not in treatment; 24% in treatment) were
      interviewed separately regarding the teen's recent use of cigarettes, alcohol,
      marijuana, and other illicit drugs. Irrespective of adolescent treatment status,
      fair-to-good congruence was found on cigarette and marijuana use, alcohol use
      frequency, and overall substance use frequency. Poor congruence was found on the
      incidence of alcohol and other illicit drug use, and the quantity of alcohol
      consumed per drinking day. Multiple regression analysis revealed that poorer
      congruence on substance use frequency occurred when the teen was younger, when
      the parent scored low on monitoring and high on psychological distress, and when
      the parent used alcohol more frequently. Results indicate that parental awareness
      of teen substance use varies with the substance used and its measurement. In the
      absence of a cooperative teen, however, parental report of the frequency of
      adolescent substance use appears to serve as a fair-to-good proxy.

PMID- 19180244
TI  - New hypotheses about postural control support the notion that all dystonias are
      manifestations of excessive brain postural function.
AB  - This paper postulates that all forms of the neurological movement disorder,
      dystonia, can be argued to reflect excessive function of one or more components
      of the brain postural system. This is based on four central arguments. First,
      because some forms of postural control are already known to be dynamic, rather
      than static, it is suggested that hyperkinetic dystonias reflect excessive
      function of dynamic postures, rather than abnormal movements. Second, the range
      of functional roles served by the postural system is hypothesized to include
      direct control of movement, suggesting a postural basis for task-specific
      dystonias. Third, by defining posture as a neural system that maintains body
      stabilization, it can be shown that the range of mechanical means of implementing
      stabilization, including co-contraction of antagonistic muscles, matches the
      range of presentations of dystonia. Fourth, it is shown that the above premises
      are able to account for previously unexplained observations in dystonia. Based on
      the inhibitory influence that stabilizing mechanisms exert on movement, it is
      suggested that the broad functional role that is here referred to as posture may
      be the function served by the indirect pathway of the basal ganglia.
      Specifically, it is proposed that this pathway centrally coordinates function of
      the distributed network of brain regions controlling posture and, in conjunction
      with the direct pathway, coordinates posture and movement.

PMID- 19180243
TI  - Enriched environment experience overcomes learning deficits and depressive-like
      behavior induced by juvenile stress.
AB  - Mood disorders affect the lives and functioning of millions each year.
      Epidemiological studies indicate that childhood trauma is predominantly
      associated with higher rates of both mood and anxiety disorders. Exposure of rats
      to stress during juvenility (JS) (27-29 days of age) has comparable effects and
      was suggested as a model of induced predisposition for these disorders. The
      importance of the environment in the regulation of brain, behavior and physiology
      has long been recognized in biological, social and medical sciences. Here, we
      studied the effects of JS on emotional and cognitive aspects of depressive-like
      behavior in adulthood, on Hypothalamic-Pituitary-Adrenal (HPA) axis reactivity
      and on the expression of cell adhesion molecule L1 (L1-CAM). Furthermore, we
      combined it with the examination of potential reversibility by enriched
      environment (EE) of JS - induced disturbances of emotional and cognitive aspects
      of behavior in adulthood. Three groups were tested: Juvenile Stress -subjected to
      Juvenile stress; Enriched Environment--subjected to Juvenile stress and then,
      from day 30 on to EE; and Naives. In adulthood, coping and stress responses were
      examined using the elevated plus-maze, open field, novel setting exploration and
      two way shuttle avoidance learning. We found that, JS rats showed anxiety- and
      depressive-like behaviors in adulthood, altered HPA axis activity and altered L1
      CAM expression. Increased expression of L1-CAM was evident among JS rats in the
      basolateral amygdala (BLA) and Thalamus (TL). Furthermore, we found that EE could
      reverse most of the effects of Juvenile stress, both at the behavioral, endocrine
      and at the biochemical levels. The interaction between JS and EE resulted in an
      increased expression of L1-CAM in dorsal cornu ammonis (CA) area 1 (dCA1).

PMID- 19180246
TI  - Asthma and Mood Disorders.
AB  - The high rate of comorbidity of asthma and mood disorders would imply the
      possibility of potential shared pathophysiologic factors. Proposed links between
      asthma and mood disorders include a vulnerability (trait) and state connection.
      Vulnerability for both asthma and mood disorders may involve genetic and early
      developmental factors. State-related connections may include obstructive factors,
      inflammatory factors, sleep impairment, psychological reactions to chronic
      medical illness, as well as exacerbation of asthma in individuals with chronic
      stress. Treatment for asthma may also exacerbate mood disorders. New research
      suggests involvement of the central nervous system in asthma and allergy. Further
      characterization of clinical, psychological, cellular and molecular
      interconnections between asthma and mood disorders is needed to better evaluate
      and treat these patients. A close collaboration between mental health
      professionals and allergists could result in improved symptom control, quality of
      life, overall functioning and ultimately, decreased mortality.

PMID- 19180247
TI  - Semiparametric estimation of covariance matrices for longitudinal data.
AB  - Estimation of longitudinal data covariance structure poses significant challenges
      because the data are usually collected at irregular time points. A viable
      semiparametric model for covariance matrices was proposed in Fan, Huang and Li
      (2007) that allows one to estimate the variance function nonparametrically and to
      estimate the correlation function parametrically via aggregating information from
      irregular and sparse data points within each subject. However, the asymptotic
      properties of their quasi-maximum likelihood estimator (QMLE) of parameters in
      the covariance model are largely unknown. In the current work, we address this
      problem in the context of more general models for the conditional mean function
      including parametric, nonparametric, or semi-parametric. We also consider the
      possibility of rough mean regression function and introduce the difference-based
      method to reduce biases in the context of varying-coefficient partially linear
      mean regression models. This provides a more robust estimator of the covariance
      function under a wider range of situations. Under some technical conditions,
      consistency and asymptotic normality are obtained for the QMLE of the parameters
      in the correlation function. Simulation studies and a real data example are used
      to illustrate the proposed approach.

PMID- 19180248
TI  - Effect of Number of Readout Channels on the Intrinsic Spatial Resolution
      Performance of a Continuous Miniature Crystal Element (cMiCE) Detector.
AB  - In this work we investigate how the intrinsic spatial resolution varies with the
      number of digitized readout channels for a 64 (8*8) channel detector using a
      statistics-based positioning algorithm. We report results for both 6 mm and 8 mm
      thick crystals. Three channel reduction schemes are explored. The simplest scheme
      is row and column summing (R-C sum) of the photomultiplier tube channels. The
      second method is to only use channels with signals above a 1% threshold of the
      total signal (1% thres). The third method is to acquire a subset of PMT channels
      determined by the maximum signal channel (zone mask). The full width at half
      maximum (FWHM) intrinsic spatial resolution results for the central and corner
      sections of the detector are presented for each of the methods. All methods
      except R-C sum performed well for the central section of the detector. The 1%
      thres and zone mask schemes showed significant improvement for the corner section
      of the 6 mm thick crystal. All methods using a single depth look-up table had
      difficulty in the corner region for the 8 mm thick crystal. We believe this is
      caused by depth dependent edge effects on the light response function. Initial
      results using a depth dependent look-up table show improved positioning
      performance.

PMID- 19180250
TI  - Simulation of Algorithms for Pulse Timing in FPGAs.
AB  - Modern Field Programmable Gate Arrays (FPGAs) are capable of performing complex
      discrete signal processing algorithms with clock rates well above 100MHz. This,
      combined with FPGA's low expense and ease of use, make them an ideal technology
      for pulse timing and are a central part of our next generation of electronics for
      our pre-clinical PET scanner systems. To that end, our laboratory has been
      developing a pulse timing technique that uses pulse fitting to achieve timing
      resolution well below the sampling period of the analog to digital converter
      (ADC). While ADCs with sampling rates in excess of 400MS/s exist, we feel that
      using ADCs with lowing sampling rates has many advantages for positron emission
      tomography (PET) scanners. It is with this premise that we have started
      simulating timing algorithms using MATLAB in order to optimize the parameters
      before implementing the algorithm in Verilog. MATLAB simulations allow us to
      quickly investigate filter designs, ADC sampling rates and algorithms with real
      data before implementation in hardware. We report our results for a least squares
      fitting algorithm and a new version of a leading edge detector of PMT pulses.

PMID- 19180249
TI  - Vulnerability in Popular Molecular Dynamics Packages Concerning Langevin and
      Andersen Dynamics.
AB  - We report a serious problem associated with a number of current implementations
      of Andersen and Langevin dynamics algorithms. When long simulations are run in
      many segments, it is sometimes possible to have a repeating sequence of
      pseudorandom numbers enter the calcuation. We show that, if the sequence repeats
      rapidly, the resulting artifacts can quickly denature biomolecules and are then
      easily detectable. However, if the sequence repeats less frequently, the
      artifacts become subtle and easily overlooked. We derive a formula for the
      underlying cause of artifacts in the case of the Langevin thermostat, and find it
      vanishes slowly as the inverse square root of the number of time steps per
      simulation segment. Numerous examples of simulation artifacts are presented,
      including dissociation of a tetrameric protein after 110 ns of dynamics,
      reductions in atomic fluctuations for a small protein in implicit solvent,
      altered thermodynamic properties of a box of water molecules, and changes in the
      transition free energies between dihedral angle conformations. Finally, in the
      case of strong thermocoupling, we link the observed artifacts to previous work in
      nonlinear dynamics and show that it is possible to drive a 20-residue, implicitly
      solvated protein into periodic trajectories if the thermostat is not used
      properly. Our findings should help other investigators re-evaluate simulations
      that may have been corrupted and obtain more accurate results.

PMID- 19180251
TI  - Resorcinarene-Encapsulated Gold Nanorods: Solvatochromatism and Magnetic
      Nanoshell Formation.
AB  - Gold nanorods (GNRs) were encapsulated and dispersed into organic solvents by
      tetrabenzylthiol resorcinarene (TBTR) and by a poly(dithiocarbamate) derived from
      tetra- N-methyl(aminomethyl)resorcinarene (TMAR-DTC), formed by the in situ
      condensation of TMAR with carbon disulfide. The latter proved to be highly
      effective at enabling the redispersion of GNRs in various organic solvents. GNRs
      encapsulated in TMAR-DTC exhibited a strong solvatochromic response, with a
      refractive index sensitivity of over 300 nm/RIU. The resorcinarene-encapsulated
      GNRs could withstand high temperatures for a short period of time, and could be
      used to nucleate the growth of magnetic nanoshells.

PMID- 19180252
TI  - Children's Road Crossing: A Window Into Perceptual-Motor Development.
AB  - Most research on perceptual-motor development has focused on changes occurring
      during infancy and toddlerhood. In this paper, we describe our work on the
      development of perceptual-motor development during late childhood and early
      adolescence in the context of an important applied problem: bicycling across
      traffic-filled roads. Specifically, we have examined the gaps between cars that
      children and adults accept when bicycling across intersections, using an
      immersive, interactive bicycling simulator. This work highlights both
      methodological advances in using immersive, interactive virtual environments to
      study perceptual-motor functioning as well as theoretical advances in
      understanding the problem of moving the self in relation to other moving objects.
      We conclude with ideas for future research and practical implications of this
      work.

PMID- 19180253
TI  - Metal-enhanced Intrinsic Fluorescence of Proteins on Silver Nanostructured
      Surfaces towards Label-Free Detection.
AB  - In recent years metal-enhanced fluorescence (MEF) using silver particles has been
      reported for a number of fluorophores emitting at visible wavelengths. However it
      was generally thought that silver particles would always quench fluorescence at
      shorter wavelengths. We now report the observation of metal-enhanced fluorescence
      of the tryptophan analogue N-acetyl-L-tryptophanamide (NATA) on silver nano
      structured surfaces. NATA is a model for the intrinsic tryptophan emission from
      proteins. We have also studied the effects of silver nanostructures on the
      emission of N-acetyl-L-tyrosinamide (NATA-tyr). In the case of NATA we observed
      increased emission, decrease in fluorescence lifetimes, and increase in
      photostability when NATA was embedded in 15 nm thick spin-casted poly(vinyl
      alcohol) film on silver nanostructured surfaces. We have also investigated the
      effects of silver nanostructures on the emission from thin poly(vilnyl alcohol)
      films containing NATA-tyr. However, we have observed no increase in fluorescence
      signal for NATA-tyr on silver nanostructures. To understand these results we
      performed numerical calculations using the Finite-Difference Time-Domain (FDTD)
      technique to model a tryptophan-wavelength dipole near a spherical silver
      particle. Our calculations reveal an enhancement of the power of the radiated
      emission by the excited-state fluorophore in proximity to a 100 nm silver
      nanoparticle covering the emission spectra of NATA and NATA-tyr. These
      calculations show a clear wavelength dependence with the specific spectral region
      displaying low-enhancement at the shorter NATA-tyr wavelength and higher
      enhancement at NATA emission wavelength. Our FDTD calculations also reveal that
      excited fluorophores in the near-field of a 100 nm silver nanoparticle can induce
      enhancement fields of varying degrees of the intensity of the near-fields around
      the particle that is dependent on the wavelength of the emission. We believe this
      enhanced near-fields play a role in our observation of MEF from metal surfaces.
      The enhanced emission of NATA on silver nanostructures suggests that the
      extension of MEF to the UV region opens new possibilities to study tryptophan
      containing proteins without labeling with longer wavelength fluorophores towards
      label free detection of biomolecules.

PMID- 19180254
TI  - Conformational Properties of Helical Protein Polymers with Varying Densities of
      Chemically Reactive Groups.
AB  - Protein engineering strategies have proven valuable for the production of a
      variety of well-defined macromolecular materials with controlled properties that
      have enabled their use in a range of materials and biological applications. In
      this work, such biosynthetic strategies have been employed in the production of
      monodisperse alanine-rich, helical protein polymers with the sequences
      [AAAQEAAAAQAAAQAEAAQAAQ](3) and [AAAQAAQAQAAAEAAAQAAQAQ](6). The composition of
      these protein polymers is similar to that of a previously reported family of
      alanine-rich protein polymers, but the density and placement of chemically
      reactive residues has been varied to facilitate the future use of these
      macromolecules in elucidating polymeric structure-function relationships in
      biological recognition events. Both protein polymers are readily expressed from
      E. coli and purified to homogeneity; characterization of their conformational
      behavior via circular dichroic spectroscopy (CD) indicates that they adopt highly
      helical conformations under a range of solution conditions. Differential scanning
      calorimetry, in concert with CD, demonstrates that the conformational transition
      from helix to coil in these macromolecules can be well-defined, with helicity,
      conformational transitions, T(m) values, and calorimetric enthalpies that vary
      with the molecular weight of the protein polymers. A combination of infrared
      spectroscopy and CD also reveals that the macromolecules can adopt beta-sheet
      structures at elevated temperatures and concentrations and that the existence and
      kinetics of this conformational transition appear to be related to the density of
      charged groups on the protein polymer.

PMID- 19180255
TI  - Vibrational echo correlation spectroscopy probes of hydrogen bond dynamics in
      water and methanol.
AB  - Multidimensional vibrational echo correlation spectroscopy with full phase
      resolution is used to measure hydrogen bond dynamics in water and methanol. The
      OD hydroxyl stretches of methanol-OD oligomers in CCl(4) and HOD in H(2)O are
      studied using the shortest mid-IR pulses (<50 fs, <4 cycles of light) produced to
      date. The pulses have sufficient spectral bandwidth to span the very broad (>400
      cm(-1)) spectrum of the 0-1 and 1-2 transitions. Hydrogen bond population
      dynamics are extricated with exceptional detail in MeOD oligomers because the
      different hydrogen bonded species are spectrally distinct. The experimental
      results along with detailed calculations indicate the strongest hydrogen bonds
      are selectively broken through a non-equilibrium relaxation pathway following
      vibrational relaxation of the hydroxyl stretch. The correlation spectra are also
      a sensitive probe of the fluctuations in water and provide a stringent test of
      water models that are widely used in simulations of aqueous systems. The analysis
      of the 2D band shapes demonstrates that different hydrogen bonded species are
      subject to distinct (wavelength dependent) ultrafast (~100 fs) local fluctuations
      and essentially identical slow (0.4 and ~2 ps) structural rearrangements.
      Observation of wavelength dependent dynamics demonstrates that standard
      theoretical approaches assuming Gaussian fluctuations cannot adequately describe
      water dynamics.

PMID- 19180256
TI  - Genotype analysis of polymorphisms in autoimmune susceptibility genes, CTLA-4 and
      PTPN22, in an acute anterior uveitis cohort.
AB  - PURPOSE: Acute anterior uveitis (AAU) is the most common form of uveitis and is
      thought to be autoimmune in nature. Recent studies have described genes that act
      as master controllers of autoimmunity. Protein tyrosine phosphatase type 22
      (PTPN22) and Cytotoxic T lymphocyte antigen-4 (CTLA-4) are two of these genes,
      and single nucleotide polymorphisms (SNPs) in the genes encoding these molecules
      have been associated with several autoimmune diseases. In this study we have
      analyzed SNPs in PTPN22 and CTLA-4 in patients with AAU. METHODS: The functional
      protein tyrosine phosphatase type 22 (PTPN22) SNP (R620W rs2476601, 1858C/T), and
      two CTLA-4 SNPs (rs5742909, -318C/T and rs231775, 49A/G) were analyzed in 140
      patients with AAU and 92 healthy controls by sequence-specific primer -polymerase
      chain reaction (SSP-PCR). Data was analyzed by chi(2) analysis and Fisher's exact
      test. RESULTS: There was no significant association between PTPN22 620W, CTLA-4 
      318C/T, or CTLA-4 49A/G and AAU. Similarly, there was no association with the
      three SNPs when patients were classified by race or gender. Finally, there was no
      association with the presence of ankylosing spondylitis in the patient cohort.
      CONCLUSIONS: The data do not support an association between SNPs in PTPN22 and
      CTLA-4, genes regarded as genetic master switches of autoimmunity. This raises
      the issue of the etiology of AAU and the possibility that it should be regarded
      as an autoinflammatory rather than an autoimmune condition.

PMID- 19180257
TI  - Localizations of visual cycle components in retinal pigment epithelium.
AB  - PURPOSE: We used immunocytochemistry and confocal microscopy to determine whether
      enzymes of the rod visual cycle were uniformly distributed in retinal pigment
      epithelium (RPE) cells. The localizations of these enzymes were compared to known
      localizations of retinoid-binding proteins and associated proteins. METHODS:
      Antibodies to proteins and enzymes associated with the rod visual cycle were used
      for fluorescence immunocytochemistry with frozen sections of albino mouse and rat
      retina. Images were obtained with a laser scanning confocal microscope. RESULTS:
      Components associated with the rod visual cycle were distributed in three
      distinct patterns in mouse and rat RPE. Three visual cycle enzymes (RDH5, LRAT,
      and RPE65) were restricted to the somata of RPE cells and were not detected
      within apical processes. Ezrin, an actin-binding protein, and ERM-binding
      phosphoprotein50/sodium-hydrogen exchanger regulatory factor1 (EBP50/NHERF1), an
      ezrin-binding PDZ-domain protein, were largely restricted to RPE apical
      processes. The fluorescence intensity over Muller cell apical processes was less
      intense. Cellular retinaldehyde-binding protein (CRALBP), which binds to
      EBP50/NHERF1, and cellular retinol-binding protein type 1 (CRBP1) were found
      throughout RPE cells and Muller cells. CONCLUSIONS: Visual cycle enzymes were
      confined to the somata of RPE cells and did not occur within the long apical
      processes, either in dark- or light-adapted animals. Other components previously
      linked to the visual cycle (EBP50/NHERF1 and ezrin) were largely confined to the
      apical processes, where they could be associated with release of 11-cis-retinal
      or uptake of all-trans-retinol. CRALBP and CRBP1 were distributed throughout the
      RPE cell, where they could mediate diffusion of retinoids between apical
      processes and somata.

PMID- 19180258
TI  - Myocilin polymorphisms and high myopia in subjects of European origin.
AB  - PURPOSE: Three previous studies have tested for an association between high
      myopia and polymorphisms in the open angle glaucoma gene, myocilin (MYOC), all in
      subjects of Chinese ethnicity. In two of the studies, a significant association
      was found while in the third, there was no association. We sought to investigate
      the association between high myopia and polymorphisms in MYOC in subjects of
      European ethnicity. METHODS: Subjects were recruited from two sites, Cardiff
      University in the UK and Duke University in the United States. The Cardiff
      University cohort was comprised of 164 families with high myopia (604 subjects)
      plus 112 unrelated, highly myopic cases and 114 emmetropic controls. The Duke
      University cohort was comprised of 87 families with high myopia (362 subjects)
      plus 59 unrelated, highly myopic cases. Subject DNA was genotyped with a panel of
      MYOC single nucleotide polymorphisms (SNPs) including those found previously
      associated with high myopia. The Cardiff cohort was also genotyped for two
      flanking microsatellite markers analyzed in prior studies. Association between
      high myopia and MYOC polymorphisms was assessed using the Unphased program.
      RESULTS: Since there was no evidence of heterogeneity in genotype frequencies
      between families and singleton samples or between cohorts, both subject groups
      (families and unrelated subjects) from both recruitment sites were analyzed
      jointly for those SNPs genotyped in common. Two variants showed significant
      association before correction for multiple testing. These two variants were
      rs16864720 (p=0.043) and NGA17 (p=0.026). However, there was no significant
      association after Bonferroni correction. The estimated relative risk (RR)
      conferred by each of the MYOC variants was low (RR<1.5). CONCLUSIONS: Our results
      suggest that MYOC polymorphisms have a very low, or possibly negligible,
      influence on high myopia susceptibility in subjects of European ethnicity.

PMID- 19180260
TI  - Tramadol: basic pharmacology and emerging concepts.
AB  - Tramadol hydrochloride is a widely prescribed, centrally acting analgesic
      marketed in over 90 countries. Before being released in the U.S. in 1995, the
      drug had been available in Europe for almost two decades. Thus, the
      pharmacokinetic and pharmacodynamic properties of tramadol have been extensively
      investigated. However, additional information about the drug continues to be
      discovered. Tramadol exists as a racemic mixture with the (+)-enantiomer and the
      (-)-enantiomer, and at least some of their metabolites, having different effects.
      Tramadol has dual mechanisms of action by which analgesia may be achieved: micro
      opioid receptor activation and enhancement of serotonin and norepinephrine
      transmission. Serotonin syndrome may occur in patients taking combinations of
      tramadol and other agents that increase serotonin activity. The relative degree
      of contribution of each mechanism toward pain control is not fully understood. By
      increasing serotonin and norepinephrine neurotransmission, tramadol may
      conceivably also exert a degree of antidepressant effect. Therefore, tramadol may
      be of particular value in patients with chronic pain who also suffer from
      depression. This drug has been shown to be beneficial in the treatment of a wide
      range of acute and chronic pain syndromes, including neuropathic pain. While
      abuse of tramadol may occur, several large studies have demonstrated that the
      incidence of abuse is rather low, about one case per 100,000 patients.

PMID- 19180259
TI  - Ceftobiprole medocaril: a new generation beta-lactam.
AB  - Ceftobiprole is a novel parenteral cephalosporin with high affinity for most
      penicillin-binding proteins, including the mecA product penicillin-binding
      protein (PBP) 2a, rendering it active against methicillin-resistant
      staphylococci. Its in vitro activity against staphylococci and multiresistant
      pneumococci, combined with its Gram-negative spectrum comparable to that of other
      extended-spectrum cephalosporins, its stability against a wide range of beta
      lactamases and its pharmacokinetic and safety profile make ceftobiprole an
      attractive new antimicrobial agent. Because of its low water solubility,
      ceftobiprole is administered intravenously as a prodrug, ceftobiprole medocaril.
      Ceftobiprole medocaril is generally well tolerated (with the exception of a
      caramel-like taste disturbance). Ceftobiprole medocaril has been evaluated in two
      phase III clinical trials for the treatment of complicated skin infections and
      skin structure infections. Its broad spectrum of activity may allow ceftobiprole
      to be used as monotherapy for some infections where combination therapy would
      otherwise be required, especially regimens requiring coverage of methicillin
      resistant Staphylococcus aureus (MRSA).

PMID- 19180261
TI  - Certolizumab pegol in Crohn's disease.
AB  - Certolizumab pegol is a humanized Fab' fragment monoclonal antibody to tumor
      necrosis factor alpha (TNF-alpha). PEGylation increases its half-life, and it is
      administered subcutaneously to treat immune-mediated inflammatory diseases such
      as Crohn's disease and rheumatoid arthritis. Certolizumab pegol improves quality
      of life and reduces clinical disease activity. Inflammatory markers such as C
      reactive protein (CRP) also decrease after administration of certolizumab pegol.
      The dose for induction of remission is 400 mg subcutaneously at weeks 0, 2 and 4.
      The dose for maintenance of remission is 400 mg sc given every four weeks. The
      safety profile is comparable with other anti-TNF agents, and the major adverse
      events are related to infections. This article reviews the published data
      regarding the efficacy and safety of certolizumab pegol.

PMID- 19180262
TI  - Montelukast sodium for exercise-induced asthma.
AB  - Exercise is the most common trigger of bronchospasm in children with asthma.
      Exercise-induced bronchoconstriction (EIB) occurs in up to 90% of individuals
      with asthma who are not under antiinflammatory treatment and in about 40% of
      those with allergic rhinitis. EIB may be an overwhelming problem in childhood and
      adolescence, when physical activity is a prominent component of daily life. The
      importance for those with asthma to maintain regular physical activity is
      recognized by asthma guidelines, which include the recommendation of full
      participation in sporting activities in their goals for the management of asthma.
      Cysteinyl leukotrienes, which are derivatives of the 5-lipoxygenase pathway of
      arachidonic acid metabolism, are important mediators of airway allergic
      inflammation and have a role in the pathogenetic mechanism of EIB. Montelukast
      sodium (Singulair, Merck & Co.) is a selective and orally active leukotriene
      receptor antagonist with demonstrated activity for treating asthma and allergic
      rhinitis. The effect of this drug in the prevention of EIB has been evaluated in
      a variety of studies in adults as well as in children. Both single-dose and
      regular-treatment studies showed that montelukast provides effective protection
      against EIB. Furthermore, chronic treatment with montelukast does not induce
      tolerance to the bronchoprotective effect over time. This aspect is particularly
      relevant for children, who tend to be active at frequent and irregular intervals
      throughout the day, and who therefore may benefit from around-the-clock
      pharmacologic protection.

PMID- 19180264
TI  - Thyroid disorders: highlights from the Annual Conference of the Society for
      Endocrinology (BES).
AB  - The Society for Endocrinology (BES) held its Annual Conference April 7-10, 2008,
      in Harrogate, UK. The meeting was devoted to different areas of endocrinology
      such as diabetes, diseases of both anterior and posterior pituitary, thyroid
      disorders, endocrine tumors and neoplasia, growth and development, reproductive
      endocrinology, obesity, abnormalities of adrenal function, neuroendocrinology,
      and other aspects of basic and molecular endocrinology.

PMID- 19180263
TI  - Oral formulations of budesonide: a novel treatment for inflammatory bowel
      disease.
AB  - Budesonide is a promising drug for a variety of documented applications and has
      potential in gastroenterology. Its unique local mechanism of delivery and
      efficient first-pass metabolism, resulting in fewer systemic adverse effects than
      with conventional glucocorticoids, makes this a desirable drug for clinical
      practice. This drug has shown promise in treating a wide spectrum of inflammatory
      diseases from inflammatory bowel disease and other colitides to autoimmune liver
      diseases. Future research should focus on ways to increase delivery methods to
      promote long-term usage for maintenance therapy for the disease entities listed
      above, as well as for other potential nongastrointestinal conditions.

PMID- 19180265
TI  - Retroviral bicistronic vectors.
AB  - The co-expression of genes can greatly enhance the efficiency and versatility of
      gene therapy applications. A variety of options exists to simultaneously express
      two genes in genetically modified cells. The most common approach relies on
      bicistronic vectors in which the genes are linked to each other by an internal
      ribosome entry site allowing co-translational expression of both cistrons. This
      review gives an overview of gene vector systems currently in use for coordinated
      expression of transgenes with particular focus on retroviral bicistronic vectors.
      The structural and functional characteristics of bicistronic vectors are
      discussed as well as factors influencing their efficiency such as the nature of
      the transgenes and the cell types in which they are expressed. Finally, the
      potential for clinical applications of retroviral bicistronic vectors in
      molecular genetics is highlighted.

PMID- 19180266
TI  - Cdc7 as a potential new target for cancer therapy.
AB  - Cdc7 kinase plays crucial roles in firing of replication origins and in proper
      maintenance of replication forks, which are the sites of DNA replication. The
      inactivation of Cdc7 causes destabilization of replication forks leading to acute
      genomic instability and induces massive cell death preferentially in cancer
      cells. Thus, Cdc7 kinase may be a promising novel target for cancer therapy.
      Indeed, the first classes of Cdc7 inhibitors have been reported and have been
      shown to be effective in delaying tumor growth in animal models.

PMID- 19180267
TI  - A new generation of neurobiological drugs engineered to overcome the challenges
      of brain drug delivery.
AB  - A new generation of multifunctional fusion proteins presents a potential solution
      to overcome the challenges associated with brain drug delivery and development of
      treatments for neurological disorders, including stroke, Alzheimer's disease,
      Parkinson's disease and inherited mucopolysaccharidosis. These biotherapeutics
      are engineered i) to cross the blood-brain barrier (BBB) following i.v.
      administration and ii) to produce a brain therapeutic effect. These fusion
      proteins are comprised of both a transport and a therapeutic domain. The
      transport domain is a monoclonal antibody (MAb) directed to an exofacial epitope
      of the BBB human insulin receptor (HIR), which uses the BBB endogenous insulin
      transport system to gain access to the brain via receptor-mediated transcytosis
      without interfering with the normal transport of insulin. Both human-chimeric and
      fully humanized versions of the anti-human HIRMAb have already been produced. The
      therapeutic domain of these fusion proteins consists of the peptide or protein of
      interest fused to the carboxyl terminus of the C(H)3 region of the heavy chain of
      the anti-human HIRMAb. A variety of HIRMAb fusion proteins were engineered aiming
      at the development of therapeutics for the central nervous system (CNS), i.e.,
      stroke and Parkinson's disease, as in the case of HIRMAb-BDNF and HIRMAb-GDNF,
      respectively, HIRMAb-IDUA for the treatment of Hurler's disease, HIRMAb-A beta
      single chain antibody for passive immunotherapy of Alzheimer's disease, and
      HIRMAb-avidin as delivery system for biotinylated drugs, like siRNAs. The
      multifunctionality of these fusion proteins has been validated in preclinical
      work, including brain update in primates. Pending further development into
      pharmacological and toxicological studies, and clinical trials, members of the
      biotherapeutic family discussed in the present review, designed to overcome the
      brain drug delivery hurdle, are positioned to become a new generation of
      neuropharmaceutical drugs for the treatment of human CNS disorders.

PMID- 19180268
TI  - Fatty acid facts, part II: role in the prevention of carcinogenesis, or, more
      fish on the dish?
AB  - Many laboratory studies suggest that n-3 fatty acids, especially the long-chain
      polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA), have antitumor effects. The mechanisms involved in their anticarcinogenic
      action include the suppression of the biosynthesis of proinflammatory molecules,
      the influence on transcription factor activity and gene expression, the influence
      on signal transduction, the alteration of hormone-stimulated cell growth and the
      suppression of the production of free radicals and reactive oxygen species. In
      general, n-6 fatty acids and their derivatives promote the production of
      proinflammatory eicosanoids, whereas n-3 fatty acids suppress this action. The
      encouraging preclinical results are only scarcely confirmed in reviews and meta
      analysis of epidemiological data roughly published before 2005. However, around
      2005, the first reports on epidemiological studies based on the assessment of the
      concentration of EPA and DHA in the erythrocyte cell membrane in individual study
      participants started to appear. Without exception, these publications demonstrate
      that higher EPA (and possibly DHA) concentrations in the cell membrane, a
      validated measure for plasma fatty acids, is associated with lower cancer risk.
      These intriguing results are confirmed by the recently published huge European
      Prospective Investigation into cancer and nutrition (N = 478,040 men and women)
      and U.S.-based Physicians Health Study (N = 22,071 men). These studies have
      unequivocally confirmed that fish intake has a favorable effect on cancer risk .
      This review aims to elucidate the various mechanisms by which n-3 fatty acids may
      affect the process of carcinogenesis. For this summary of knowledge, we focus on
      the effects of n-3 intake on the risk of breast cancer, prostate cancer and
      colorectal cancer.

PMID- 19180269
TI  - Molecule of the month. Tecovirimat.

PMID- 19180270
TI  - Current research in drug metabolism, drug transport and drug development.
AB  - The field of drug metabolism, drug transport and drug development is rapidly
      advancing. The fast progress of genomic knowledge, as well as improvements and
      development of novel methods, makes this field particularly dynamic. These
      advancements encompass the understanding of epigenetics in the regulation of the
      enzymes, novel animal model systems that allow the study of endogenous and
      exogenous function of the gene products, the development of P450 enzymes as drug
      targets and novel methods for studying ADME aspects during drug development. In
      order to give an update of the current situation in the field, the 17th
      International Symposium of Microsomes and Drug Oxidations, chaired by Larry
      Kaminsky, was held in Saratoga July 6-10, 2008, attracting 310 participants. The
      meeting consisted of 8 plenary sessions, 12 symposia with a total of 60 lectures
      and 185 abstracts. This report provides a summary of the meeting.

PMID- 19180271
TI  - [Evaluation in health interventions: looking for balance between internal
      validity of results and external validity of conclusions].

PMID- 19180273
TI  - [Outliers and robust logistic regression in Health Sciences].
AB  - Logistic regression methods have many applications in Health Sciences. There is a
      vast literature about procedures to be followed and the way to find the
      estimators for the parameters from the observed values, and these methods are
      implemented to all the usual statistical packages. These estimators are of the
      'maximum likelihood' kind, i.e., they are the ones that make the observed values
      the most probable among all the models that could have been used. The good
      properties of the maximum likelihood estimators are widely demonstrated. However,
      there are some practical circumstances that may cause the presence of 'outliers',
      i.e., observed values not corresponding to the logistic model we are assuming as
      a hypothesis. Occasionally, these anomalous observations can have a strong effect
      on the fit, and lead the study to the wrong conclusion. The causes of these
      outliers depend on the particular study, but it is possible to point out
      classification errors, observations (subjects) with special features which have
      not been taken into account, uncertainty in the measurement of some parameters,
      etc. The problem with maximum likelihood estimators is that they are not
      'robust', i.e., their sensitivity to outliers could be arbitrarily large, and a
      minority of outliers could lead to a wrong logistic model. In this work, we will
      show two cases illustrating possible consequences, and we will discuss the
      application of robust methods.

PMID- 19180272
TI  - [European Guidelines on Cardiovascular Disease Prevention in Clinical Practice:
      CEIPC 2008 Spanish adaptation].
AB  - We present the Spanish adaptation from the CEIPC of the European Guidelines on
      Cardiovascular Disease Prevention in Clinical Practice 2008. This guide
      recommends the SCORE model for risk evaluation. The aim is to prevent premature
      mortality and morbidity due to CVD by means of dealing with its related risk
      factors in clinical practice. The guide focuses on primary prevention and
      emphasizes the role of the nurses and primary care medical doctors in promoting a
      healthy life style, based on increasing physical activity, change dietary habits,
      and non smoking. The therapeutic goal is to achieve a Blood Pressure <140/90
      mmHg, but among patients with diabetes, chronic kidney disease, or definite CVD,
      the objective is <130/80 mmHg. Serum cholesterol should be <200 mg/dl and cLDL
      <130 mg/dl, although among patients with CVD or diabetes, the objective is <100
      mg/dl (80 mg/dl if feasible in very high-risk patients). Patients with type 2
      diabetes and those with metabolic syndrome must lose weight and increase their
      physical activity, and drugs must be administered whenever applicable, with the
      objective guided by BMI -body mass index- and waist circumference. In diabetic
      type 2 patients, the objective is glycated haemoglobin <7%. Allowing people to
      know the guides and developing implementation programs, identifying barriers and
      seeking solutions for them, are priorities for the CEIPC in order to put the
      recommendations into practice.

PMID- 19180274
TI  - [Professional debate on shortage of physicians].
AB  - We do not know the best answer to problems due to shortage of physicians
      (absolute number and by specialities) but perhaps what is important is the lack
      of a professional debate about what means 'to be' a physician. In this paper we
      address four key professional questions: 1/ the over-training of physicians when
      health demand now includes minor problems, 2/ predominance of physician-patient
      direct encounters in a world of telecommunications and indirect encounters, 3/
      the need to delegate power and responsibilities to other health professionals as
      a consequence of new technology developments and changes in role-design, and 4/
      too much emphasis in diagnosis with the danger to initiate cascades with its side
      effects. Practical answers to these questions require changes in pre and
      postgraduate education, improvement in health services organization to profit the
      use of telecommunications and analysis and re-design of the limits in between
      professions, levels of care, institutions and health and social sectors.

PMID- 19180275
TI  - [Protective effects of social networks on disability among older adults in Madrid
      and Barcelona, Spain, in 2005].
AB  - BACKGROUND: The loss of autonomy at advanced ages is not only associated with
      ageing, but also with the characteristics of the physical and social environment.
      Recent investigations have shown that social networks, social engagement and
      participation act like predictors of disability among the elderly. To analyze the
      effect of social networks on the level of autonomy (instrumental and basic
      disability) at initial stages of the old age. METHODS: The source of data is the
      first wave of the survey 'Processes of Vulnerability among Spanish Elderly',
      carried out in 2005 to a sample of 1,250 individuals? with the later purification
      of the data, it was in a size final sample of 1.244 individuals? The population
      object of study is the cohort aged 70 to 74 years in metropolitan areas (Madrid
      and Barcelona) and not institutionalized. Disability is measured by the
      development of basic activities of daily life (ADL), and instrumental activities
      of daily life (IADL). The structural aspects of the social relationships are
      measured through the diversity of social networks and participation, for which a
      global indicator of social network diversity was built. RESULTS: For each unit
      that diminishes the indicator of social network diversity, the probability of
      suffering an instrumental disability? in front of not suffering any disability?
      is multiplied by 0.97 (IC95% 0.95 - 0.99), and the probability of suffering a
      basic disability is multiplied by 0.91 (IC95% 0.87 - 0.94). DISCUSSION: Like in
      other geographic scopes, a statistically significant relationship exists between
      the indicator of diversity of social network used and the disability, in its two
      levels of graveness. Therefore, the diversity of the social network seems to show
      a protective effect in front of the disability among the Spanish urban population
      at the beginning of the age.

PMID- 19180276
TI  - [Dependence profile in Spain: an analysis from the disability survey of 1999].
AB  - BACKGROUND: In the next future an important demographical ageing will imply a
      rise in the levels of co morbidity, disability and dependence of the population.
      The objective if this work was to estimate the dependences profile by means of
      assessing the levels of severity of the disability in the Spanish general
      population. METHODS: Data come from the disease, disability and health status
      survey of 1999 of the Spanish Institute for Statistics, which includes 36
      limitations with an score of severity (from 0= absence to 4= unable). These
      limitations were grouped in five kinds of disability, the mean score of severity
      was computed for each one, and grouped in five levels of dependence. To check the
      relationship between limitations and severity an analysis of correspondence was
      performed. To identify the pattern of dependence a multiple correspondence and a
      clusters analysis were computed using the variables of age, sex, kind of
      disability and level of dependence. RESULTS: There is a relationship between
      severity and some limitations (being the limitation on daily activities
      associated to the highest severity). Five groups of dependent people were
      identified. Those with lower dependence were middle aged, men and having
      sensorial disabilities and those with higher dependence were mainly women, older
      than 80 and with disabilities on mobility and on the activities of daily living.
      CONCLUSIONS: There are five groups of dependent population and this study allows
      estimating its frequency among the general population what will be very useful to
      evaluate the amount of resources necessary to take care of them.

PMID- 19180277
TI  - [Psychosocial risk exposure among wage earning population in Spain (2004-05):
      reference values of the 21 dimensions of COPSOQ ISTAS21 questionnaire].
AB  - BACKGROUND: Reference values of all the 21 psychosocial scales or dimensions (73
      items) of the psychosocial risk assessment questionnaire COPSOQ ISTAS21 are
      computed from a representative sample of the wage earning population in Spain.
      METHODS: Representative sample of the Spanish wage-earning population, n=7,612.
      The sampling was multi-stage by conglomerates. The information was obtained by
      the administration of a standardized questionnaire in the household during 2004
      2005. All 21 scales were standardized and three punctuation levels were
      established and labelled as 'more favourable to health (or green)', 'intermediate
      (or yellow)' and 'more unfavourable to health (or red)' according two criteria:
      1) to obtain groups that follow a tertiles theoretical distribution and 2) to get
      the 'red' and 'green' groups as equilibrated as possible. RESULTS: Response rate
      was 60. Predictability dimension showed the wider difference between 'green' and
      'red' proportions (7.14). Role clarity concentred the 35.06 % of population
      between 100 and 93.75 points, and Sense of community the 29.6% between 100 and
      91.67. Double presence and hiding emotions grouped the 34.02% and the 27.74% % of
      population between 0 and 12.5 points, respectively. CONCLUSIONS: 2005 upgraded
      representative reference values of the 21 COPSOQ ISTAS21 psychosocial dimensions
      for the wage earning population in Spain are available, necessary premise to
      diagnose risk situations and prioritize the needed preventive actions at company
      level.

PMID- 19180278
TI  - [The influence of parents on habits and substance use in adolescents of Palma de
      Mallorca, Spain, in 2003].
AB  - BACKGROUND: Substance use is quite common among adolescents. The objective of
      this study was to determine the influence of parents on their habits. METHODS:
      The study sample was made up of all 13 to 15 year old schoolchildren from the
      island of Majorca and their parents. Information was collected, with validated
      instruments, on parents and adolescents alcohol intake, smoking, socioeconomic
      status, sports and television watching, as well as adolescents academic
      performance. RESULTS: The study included 4,019 schoolchildren and 7,359 parents.
      Parents belonging to a low socioeconomic level was the principal variable related
      to parental influence on smoking children (OR=3.86, 95% CI: 2.30-6.48, p=0.000),
      drinking (OR = 1.88, 95% CI: 1.40-2.54; p=0.000), failing courses (OR=6.37, 95%
      CI: 4.23-9.61; p=0.000), watching TV 2 hours/day (OR=1.97; 95%IC:1.69-2.29;
      p=0.000), and not practicing sports (OR=0.55, 95% CI: 0.38-0.80; p=0.001).
      Additionally, the mothers drinking had an influence on the children's smoking
      (OR=1.76, 95% CI: 1.24-1.51; p=0.002), and the parents smoking had an influence
      on the children's (boys, not girls) failing courses (OR=1.89, 95% CI: 1.33-2.68;
      p=0.000). The corresponding habits in parents increased the probability that
      adolescents drank (OR=1.91, 95% CI: 1.43-2.51; p=0.000), watched TV 2 hours/day
      (OR=1.97, 95% CI: 1.68-2.29; p=0.000), and practiced sports (OR=6.67, 95% CI:
      2.57-14.96; p=0.000). CONCLUSIONS: A low socioeconomic level is associated with a
      greater risk of smoking, drinking, failing courses and not practicing sports in
      the adolescents. Additionally, the mothers drinking is associated with a greater
      risk of her children smoking and drinking, and both parents drinking is
      associated with a greater risk of their children doing so. The practice of sports
      and the time spent watching television by the parents have an influence on the
      corresponding habits in their children, but have no influence on the adolescents
      smoking or drinking.

PMID- 19180279
TI  - [Health Surveillance Guide of workers using video display terminals: evaluation
      from a visual health perspective].
AB  - BACKGROUND: Visual health surveillance is essential in the protection of workers
      who use video display terminals (VDT). In Spain, the most used is the Specific
      Health Surveillance Guide published in 1999 by the Ministry of Health. The
      increase of the scientific production upon computer related occupational visual
      hazards and the experience in its applicability during the last decade justify
      the aim of this work: reviewing the quality of the guide from the point of view
      of visual health. METHODS: A consensus strategy was used among nine experts by
      means of a mixed groupal technique in two consecutive stages combining some
      aspects of the Delphi method and of the nominal group: individual evaluation of
      the guide using the consensus guide made by the authors based on the AGREE
      instrument and the subsequent meeting in order to reach an agreement and to fix
      the final recommendations for improving it. For the analysis the standardized
      score of the review domains was calculated: scope and purpose, stakeholder
      involvement, rigour of development, clarity and presentation and applicability.
      It was also calculated for the items.' Concordance in the answers of the experts
      was also analyzed. RESULTS: All domains obtained scores under 50%. The
      applicability, rigour and stakeholder involvement during the development of the
      guide, where the most deficient domains. Six out of the nine experts would not
      recommend the guide and think it should be remade. CONCLUSIONS: The guide does
      not reach the necessary quality for the surveillance of the visual health of the
      workers who use VDT. Efforts must be focussed to improve the guide.

PMID- 19180280
TI  - [Geographical bias in the inhospital mortality estimated by the Hospital
      Morbidity Survey].
AB  - BACKGROUND: The Hospital Morbidity Survey (EMH) includes, at the moment, 85% of
      hospitals and 90% of discharges, and is the only national data source that allows
      to deepen with information about diagnostics, gender or age, in the study of
      hospitals as place of death. This work aims to analyze the presence of inhospital
      mortality geographical biases in the EMH in relation to the sample universe
      represented by the Statistics of Health Establishments with Inpatient Regime
      (EESCRI). METHODS: We compared, for each province in 2004, the EMH estimations
      for discharges, deaths and the percent of mortality with the data from the
      EESCRI, and adjusting one linear regression model for the number of deaths and a
      second model for the percent of mortality. RESULTS: The EMH infraestimated the
      volume of discharges and deaths (-8.6% and -11.4%), but not the inhospital
      mortality rate (3.55% vs. 3.45%). In spite of the excellent correlation in the
      number of deaths, figures in the EMH are inferior to the EESCRI figures in most
      provinces, and in 13 provinces the discrepancies overcome the 20%. The percent of
      mortality showed discrepancies overcoming 20% in 9 provinces. CONCLUSION: In
      2004, the EMH infraestimates the discharges and deaths figures but, except for 9
      provinces, there are not evidence of important biases in the percent of
      mortality.

PMID- 19180283
TI  - Inappropriate use of emergency services: a systematic review of prevalence and
      associated factors.
AB  - This systematic review aimed to measure the prevalence of inappropriate emergency
      department (ED) use by adults and associated factors. The review included 31
      articles published in the last 12 years. Prevalence of inappropriate ED use
      varied from 20 to 40% and was associated with age and income. Female patients,
      those without co-morbidities, without a regular physician, without a regular
      source of care, and those not referred to the ED by a physician also showed more
      inappropriate ED use, with the relative risk varying from 1.12 to 2.42.
      Difficulties in accessing primary health care (difficulties in setting
      appointments, longer waiting periods, and short business hours at the primary
      health care service) were also associated with inappropriate ED use. Thus,
      primary care requires fully qualified patient reception and efficient triage to
      promptly attend cases that cannot wait. It is also necessary to orient the
      population on situations in which they should go to the ED and on the
      disadvantages of consulting the ED when the case is not really urgent.

PMID- 19180281
TI  - [Utilization of growth hormone in Valencia Region, Spain, during the period 2003
      2007].
AB  - BACKGROUND: The main goal is to analyze the evolution of the consumption of
      growth hormone (Somatropin) at the Valencia region (Spain). The research focuses
      on the period comprising 2003-2007 and aims at assessing the impact of the change
      in the conditions of dispensation of the hormone (May 2005) as well as of the
      approval of a new indication in 2004. We have also studied the number of treated
      patients and expenses saved in public money due to the denial of certain
      treatments. METHODS: The patient data have been obtained from a proprietary
      database owned by the regions government, this database contains information
      about the requests for treatment and the consumption of growth hormone has been
      obtained from database Gaia and drug consumption in the hospital. The data are
      expressed in terms of number of treated patients, consumed milligrams and cost.
      RESULTS: The number of patients treated with growth hormone has increased 50%
      (from 346 patients in 2003 to 520 in 2007). The denial of requests for treatment
      has made it possible to save 3.912.253 capital JE, Ukrainian. The cost per mg of
      growth hormone has decreased from 27.35 capital JE, Ukrainian in 2003, when the
      hormone was dispensed in local pharmacy stores, to 22.34 capital JE, Ukrainian in
      2007, when it was dispensed at hospitals pharmacies. The change in the conditions
      in which the drug is dispensed has led to a reduction of 18.3% considering
      current costs. CONCLUSIONS: The number of treated patients has increased a 50%
      from 2003 to 2007. In this period of time has been approved a new indication. The
      cost/mg has been reduced a 18,3 % due to the change in the conditions of
      dispensation. The Advisory Committee has contributed to the utilization of growth
      hormone according to rational drug use criteria.

PMID- 19180284
TI  - [The cost of violence for the public health system in Brazil: available data and
      possibilities for estimation].
AB  - The Brazilian public budget for health was R$ 53 billion (approximately U$ 20
      billion) in 2003. What share of this total was to treat victims of violence? It
      is impossible to estimate that proportion directly, due to limitations in the
      available data. This paper proposes a methodology to estimate the cost of
      violence for the public health system, using data from the Unified National
      Health System, the government budget, and the demand for public medical services
      (National Household Sample Survey). According to our estimates, in 2004 the costs
      of treatment for victims of external causes, aggressions, and traffic accidents
      were R$ 2.2 billion, R$ 119 million, and R$ 453 million, respectively. These
      findings were approximately four times higher than those observed in other
      studies.

PMID- 19180285
TI  - [Oral health of Guarani Indians in the State of Rio de Janeiro, Brazil].
AB  - The aim of the present study was to describe the oral health conditions of
      Guarani Indians in the State of Rio de Janeiro, Brazil. A cross-sectional oral
      health survey was conducted in 508 subjects (90.7% of the Guarani population)
      using World Health Organization criteria. At 5 years of age, 38.5% of children
      were caries-free. DMF-T was 1.7 at 12 years. 54.2% of subjects in the 35-44-year
      group and 12% in the 65-74-year group had at least 20 teeth. Numbers of teeth for
      the 35-44 and 65-74 age groups were 18.5 and 8.5, respectively. While caries
      index did not differ by gender for deciduous teeth, DMF-T and tooth loss was
      higher in women. Nearly 60% of the population showed no periodontal illness.
      Gingival bleeding and calculus were the most severe periodontal conditions.
      Gingival bleeding and calculus were more common in men and excluded sextants more
      common in women. Oral health promotion strategies are needed for this ethnic
      group and should consider the epidemiological profile according to age and
      gender.

PMID- 19180286
TI  - [Brazilian Oral Health Survey (SB Brazil 2003): data do not allow for population
      estimates, but correction is possible].
AB  - The Brazilian Oral Health Survey (SB Brazil 2003) was the most comprehensive
      study on oral health conditions ever conducted in Brazil. Probabilistic sampling
      methods were applied in order for the collected data to represent the population
      age groups selected in the 5 regions of the country. However, this was not
      possible because the sampling process was never concluded, which would require
      estimation of the sample weights and identification of the sample's other
      structural variables (selection strata and primary sampling units). This paper
      describes the SB Brazil 2003 sample design, formulates the inclusion
      probabilities in the multiple selection stages, and proposes strategies for
      estimating the sample weights. The strategy to define the sample weights and
      identify the sample's structural variables hinges on retrieving data that should
      have been recorded in the reports produced during the survey, and in their
      absence, in information available from the Brazilian Institute of Geography and
      Statistics (IBGE) and Ministry of Education and Culture (MEC), as valid proxies.

PMID- 19180287
TI  - Common mental disorders and chronic non-communicable diseases in adults: a
      population-based study.
AB  - A cross-sectional population-based study was conducted to identify the prevalence
      of common mental disorders and verify the association with chronic non
      communicable diseases (NCDs) and the self-reported number of chronic diseases.
      The Self-Reporting Questionnaire (SRQ-20) was applied in a multi-stage random
      sample of 1,276 adults aged 40 and older. Socio-demographic, behavioral, and
      health-related variables were also obtained using a structured questionnaire.
      Prevalence of common mental disorders was 30.2%. Lower schooling and social class
      and the 46-55-year age bracket were associated with psychiatric morbidity. Each
      chronic illness was independently associated with common mental disorders.
      However, a stronger association was found between common mental disorders and the
      total number of self-reported chronic conditions, with a prevalence ratio of 4.67
      (95%CI: 3.19-6.83) for five or more self-reported NCDs. The current study
      emphasizes the importance of common mental disorders in chronically ill patients,
      particularly in those with more total chronic conditions.

PMID- 19180288
TI  - Which empowerment, which Health Promotion? Conceptual convergences and
      divergences in preventive health practices.
AB  - Based on the multiple meanings, 'empowerment' can be identified with either
      conservative or critical Health Promotion approaches. From a conservative
      approach, the concept is viewed as an essentially individual phenomenon, centered
      on the provision of information and the external transfer of power in the name of
      the collective good. From this approach, the relationship between 'psychological'
      and 'community' empowerment is not considered. From a critical approach, the
      concept is viewed as a relational phenomenon that manifests itself in the
      dialectic conflict of interests between individuals, groups, and social classes.
      From this approach, 'psychological' and 'community' empowerment are seen as micro
      and macro levels of analysis, and social transformations are the result of
      simultaneous changes at these levels. The use of the notion of empowerment
      without critical reflection or political analysis of power relations in society
      disseminates vague, romantic, and homogeneous views of 'community'. Therefore, to
      assume the relational nature of empowerment means to accept its interdependence
      with the notion of participation, without which there can be no social
      transformation. Thus, one should be vigilant about multiple meanings that
      empowerment can given in Health Promotion discourse.

PMID- 19180289
TI  - [Spatial distribution of elderly individuals in a medium-sized city in Sao Paulo
      State, Brazil, according to key socio-demographic and morbidity characteristics].
AB  - Geographic Information Systems serve as important public health tools for
      analyzing population disease distribution and thus for identifying individuals
      with chronic non-communicable diseases. The current study performed a spatial
      analysis of the distribution of the population 60 years and older in the city of
      Botucatu, Sao Paulo State, Brazil, studying the socio-demographic profile and the
      presence of diabetes mellitus and arterial hypertension. Data were analyzed from
      468 elderly individuals from a population survey conducted in 2001-2002. Elders
      with the highest socioeconomic status live in the census tracts with the highest
      social strata, as proven statistically by spatial analysis techniques for income
      and schooling. No spatial distribution pattern was found for elderly individuals
      with hypertension and diabetes, who were located heterogeneously on the map. The
      study suggests the use of geoprocessing techniques for digital mapping of areas
      covered by primary health care units, aimed at better monitoring of the
      distribution of elderly individuals with chronic diseases and their care by
      health professionals.

PMID- 19180290
TI  - [Patient satisfaction with pharmacy services: translation and validation of the
      Pharmacy Services Questionnaire for Brazil].
AB  - The aim of this study was to translate into Portuguese and validate the Pharmacy
      Services Questionnaire (PSQ). The instrument includes 20 questions that measure
      user satisfaction with pharmacy services, and is organized according to two
      factors. It uses a Likert scale of answers from 1 (poor) to 5 (excellent). The
      PSQ-Brazil was applied to 137 diabetics from 31 to 89 years of age (60.6% women),
      clients of private pharmacies, mostly users of public health services (65.7%),
      with low education (67.9% elementary schooling or less), and who used an average
      of 4.3 medicines per person. Overall score in the sample was 3.6 (SD = 1.1 [95%CI
      3.4-3.8]). After factor analysis, 'pleasant exposure' and 'treatment management'
      included 8 and 12 items, respectively, and were significantly correlated with
      each other (r = 0.92, p < 0.001) and with the overall score. The instrument
      obtained a Cronbach's alpha of 0.98 for the overall score. The pleasant exposure
      and treatment management variables showed alphas of 0.94 and 0.98. PSQ-Brazil
      shows adequate reliability and validity for use in the country.

PMID- 19180291
TI  - A serological and molecular investigation of American cutaneous leishmaniasis in
      dogs, three years after an outbreak in the Northwest of Parana State, Brazil.
AB  - Classic and molecular (polymerase chain reaction--PCR) techniques were used to
      diagnose American cutaneous leishmaniasis in 149 dogs from an area in the
      northwest of Parana State, Brazil, where an American cutaneous leishmaniasis
      outbreak occurred in 2002. The results were compared to a set of previously
      obtained results. Twenty-five dogs had positive indirect immunofluorescence (IIF)
      (titers > or = 40), including two animals with suggestive lesions. The percentage
      of dogs with positive IIF was similar to that found in a previous study. The
      cultures of the lesion, blood and bone marrow were negative for Leishmania. A
      direct search for the parasite in the lesions proved negative, although PCR tests
      were positive. The PCR did not detect the DNA of Leishmania (Viannia) in the
      blood, even for those that had positive PCR in a previous study. The follow up of
      the 27 dogs showed that the majority of them had maintained the same levels of
      antibodies that had been detected previously. There was a reduction in the number
      of dogs with lesions, probably due to the transmission control measures that were
      adopted after the outbreak.

PMID- 19180292
TI  - [Importance of the Teratogen Information Service in Bahia, Brazil, for prevention
      of congenital malformations: an initial four-year review].
AB  - Teratogenic agents are defined as physical, chemical, or biological agents or
      nutrient deficiencies that lead to fetal structural or functional alterations.
      Information on the effects of exposure to teratogens during pregnancy is of the
      utmost importance. In order to achieve this goal, in 2001, the Bahia State
      Teratogen Information Service was created in the Medical Genetics Department at
      the University Hospital of the Federal University in Bahia. The current paper
      aimed to describe the first four years of operation in the service. From March
      2001 to May 2005, the service was consulted by telephone, fax, and e-mail. During
      this period, 408 queries were made, for a total of 1,091 different reasons. Most
      queries were made by pregnant women and health care professionals. Hair products,
      herbal teas, and misoprostol were the most widely investigated agents. The low
      number of queries (average 1/day) shows the need for more awareness-raising on
      the risks posed by the various agents.

PMID- 19180293
TI  - [Prevalence of risk factors for cardiovascular diseases in an urban male
      population in Southeast Brazil].
AB  - Surveillance of cardiovascular risk factors has been recommended worldwide. The
      current study aimed to estimate the prevalence of smoking, overweight/obesity,
      insufficient physical activity, arterial hypertension, and pre-hypertension among
      men covered by the Family Health Program in urban Juiz de Fora, Minas Gerais
      State, in Southeast Brazil. A household survey was performed with a systematic
      sample of 217 men 20 to 49 years of age, from a list of residents within this age
      range. Prevalence of risk factors was high, with overweight/obesity the most
      frequent (43.3%; 95%CI: 36.6-50.2). Men classified as sedentary or with irregular
      physical activity totaled 28% (95%CI: 22.2-34.6). Smoking was reported by 25.3%
      (95%CI: 19.7-31.7). Overt hypertension was present in 24% (95%CI: 18.4-30.2) and
      borderline hypertension in 19.4% (95%CI: 14.3-25.2). Two or more simultaneous
      risk factors were found in 45.2% of the sample. The high prevalence rates suggest
      that health promotion strategies need to be intensified in the male population.

PMID- 19180294
TI  - [Association between mode of delivery and maternal complications in a public
      hospital in Greater Metropolitan Sao Paulo, Brazil].
AB  - The purpose of this study was to assess the relationship between mode of delivery
      and maternal complications, based on a retrospective cohort of all births at a
      public hospital in 2003. Complications included: infection, hemorrhage,
      hysterectomy, uterine rupture, lesions in adjacent organs, deep venous
      thrombosis, and pulmonary embolism. The analysis used odds ratio (OR), chi
      squared test, and Fisher's exact test, besides logistic regression. Fifteen
      complications were identified. Taking vaginal delivery as the reference, an
      association was found between cesarean section and overall complications.
      Analysis of confounding showed an association between hypertension, HIV, placenta
      previa, and abruptio placentae. After controlling for these variables, an
      association remained between overall complications and cesarean section (OR =
      9.7; p = 0.04). Another analysis comparing elective cesareans and vaginal
      deliveries also showed an increased risk for cesarean (OR = 4.7; p = 0.02).
      Finally, comparing elective cesareans with trial of labor, we found an increased
      proportion of complications in elective cesareans, with borderline significance
      (OR = 3; p = 0.058). We concluded that cesarean section is associated with
      maternal morbidity, even after controlling for confounders.

PMID- 19180295
TI  - [Sexuality, bodily experiences, and gender: an ethnographic study of persons
      living with HIV in Greater Metropolitan Buenos Aires, Argentina].
AB  - Based on the results of an ethnographic study on daily experience with HIV in
      Greater Metropolitan Buenos Aires, Argentina, the article discusses behavioral
      approaches that reduce the sexuality of persons living with HIV to an issue of
      safety and protection. By articulating a social construction perspective and the
      notion of hegemony, the author proposes that sexuality can be understood as a
      process of individual and social construction shaped by power relations and
      social regulations. The analysis of the experiences of living with HIV in
      marginalized populations shows how chronic social inequality, violence,
      discrimination, and stigmatization generate particular characteristics of sexual
      issues. These social processes become driving forces that shape sexual experience
      as a field of danger, repression, and restriction rather than pleasure and
      exploration. Finally, daily confrontation with social metaphors places strain on
      gender relations, practices, and identities.

PMID- 19180296
TI  - [Suicide planning among teenage students: prevalence and associated factors].
AB  - This cross-sectional study evaluated the prevalence of suicide planning and
      associated factors in a representative sample of 12- to-18-year-old students in
      Porto Alegre, Rio Grande do Sul State, Brazil. Two self-administered
      questionnaires were used to collect data: a questionnaire, standardized by the
      World Health Organization, about use of alcohol and drugs, violence, feelings of
      loneliness and sadness, family relationships, suicide planning, behavior in
      school, and relationships with friends; and the Body Shape Questionnaire.
      Prevalence of suicide planning was 6.3%. Multivariate analysis using Cox
      regression showed that the prevalence of suicide planning was higher among girls
      and among adolescents that reported problems in the relationships with their
      parents. Drug use by friends and having a small number of close friends increased
      suicide planning by 90% and 66%, respectively. Prevalence of suicide planning was
      two to three times greater among adolescents bullied by classmates or who
      reported feelings of loneliness or sadness. Adverse family relationships,
      aggressive interactions with classmates, and depressive symptoms increase the
      prevalence of suicide planning. Therefore, preventive measures should be
      developed in schools and should include the family.

PMID- 19180297
TI  - [Detection and differentiation of Entamoeba histolytica and Entamoeba dispar by
      polymerase chain reaction in a community in Zulia State, Venezuela].
AB  - Differential identification of Entamoeba histolytica and Entamoeba dispar is
      essential for both appropriate patient treatment and epidemiological purposes. To
      determine the prevalence of these amoeba infections in Santa Rosa de Agua
      (Maracaibo, Zulia State, Venezuela), a PCR assay using specific primers for each
      species was standardized and applied. 204 stool samples were analyzed through
      direct microscopic examination with SSF (0.85%) and lugol, formol-ether
      concentration, and PCR. Under direct microscopy, 42 individuals (20.58%)
      presented the E. histolytica/E. dispar complex. Meanwhile PCR showed 47 positive
      cases for these amoebas: 22 E. histolytica (10.78%), 16 E. dispar (7.84%), and 9
      (4.41%) mixed infections. There was no significant difference in the presence of
      E. histolytica and/or E. dispar according to either gender or age. There were no
      cases of these amoebas in children under 2 years of age. Observed frequency of E.
      histolytica (31/204) shows the endemic nature of amoeba infection in this
      community.

PMID- 19180298
TI  - [Association between iron supplementation during pregnancy and prematurity, low
      birth weight, and very low birth weight].
AB  - The objective was to evaluate the association between prophylactic iron
      supplementation and prematurity and low birth weight. Pregnant women 20 years and
      older with 21 to 28 weeks of gestational age were enrolled consecutively in
      prenatal services in the Unified National Health System in six Brazilian State
      capitals between 1991 and 1995. Socio-demographic data and information on iron
      supplementation up until the 28th gestational week were obtained by means of an
      interview. Outcomes and other variables were collected from medical records.
      Anemia was present in 31.3% of the 3,865 women. Among anemic women (hemoglobin <
      11.0g/dL), 29.8% were taking iron supplements, as compared to 16.7% among non
      anemic women (hemoglobin > or = 11.0g/dL). After adjusting for potential
      confounders, iron was not associated with prematurity (OR = 0.88; 95%CI: 0.73
      1.07), low birth weight (OR = 0.99; 95%CI: 0.75-1.31), or very low birth weight
      (OR = 0.58; 95%CI: 0.29-1.13). The results suggest that iron supplementation up
      to the 28th gestational week does not reduce the risk of prematurity, low birth
      weight, or very low birth weight.

PMID- 19180299
TI  - [Users' and community leaders' perceptions of their capacity to influence the
      quality of health care: case studies of Colombia and Brazil].
AB  - Health system reforms in Colombia and Brazil introduced policies that promote
      social participation in health care quality control. The objective of this paper
      was to analyze users' and leaders' perceptions of their capacity to achieve
      changes in the countries' health services. An exploratory and descriptive
      qualitative study was performed with individual interviews and focus groups of
      users and leaders in Colombia and Brazil. Most informants perceived themselves as
      having the capacity to induce changes to improve the quality of health services.
      They attributed this capacity primarily to internal factors related to their
      participatory behavior, plus only one external factor, the availability of
      institutional participatory spaces. The lack of capacity to influence change was
      only related to passive attitudes and fear of retaliation in Colombia. The
      existence of a population with high self-perceived capacity to achieve change
      appears as a potential factor to be strengthened, while institutional democratic
      space needs to improve in order to enhance the effectiveness of social
      participation in health policies.

PMID- 19180300
TI  - Frequency and characteristics of induced abortion among married and single women
      in Sao Paulo, Brazil.
AB  - This article presents the results of a study in the city of Sao Paulo, Brazil,
      aimed at estimating the frequency of induced abortion among women 15 to 49 years
      of age. The objective was to characterize the occurrence of induced abortion by
      comparing the ideal number of children, age, and contraceptive use between
      married and single women. Based on random sampling, 1,749 interviews were held,
      including 764 married women, 658 single women, and 327 with other marital status.
      The analysis included: mean number of abortions per woman by analysis of variance
      and proportions of abortions and pregnancy, using the chi-square test. The mean
      abortion rate for married women (45 per thousand) did not differ statistically
      from that of single women. However, the pregnancy rate was much lower in single
      women, and when single women became pregnant they used abortion more frequently;
      while fewer than 2% of pregnancies in married women ended in induced abortions,
      among single women the abortion rate exceeded 18%. Therefore, the priority in the
      reproductive health field should be to invest in the supply and dissemination of
      appropriate contraceptive methods for women's early sexually active life.

PMID- 19180301
TI  - [Prevalence of sickle cell trait and sickle cell anemia among newborns in the
      Federal District, Brazil, 2004 to 2006].
AB  - To determine the prevalence of sickle cell trait and sickle cell anemia among
      newborns in the Federal District, Brazil, a cross-sectional prevalence study
      covering the years 2004 to 2006 was conducted. Test results reported from the
      Neonatal Screening Program in the Federal District Health Department from 2004 to
      2006 were analyzed, and prevalence rates were calculated. Neonatal blood samples
      were tested by isoelectric focalization. From January 2004 to December 2006,
      116,271 newborns were tested for hemoglobinopathies, corresponding to 85% of all
      live births from mothers residing in the Federal District. The study identified
      3,760 newborns with sickle cell trait (Hb AS) and 109 with sickle cell anemia (Hb
      SS). The prevalence rates were 323 (Hb AS) and 9 (Hb SS) per 10,000 live births.
      The high prevalence of sickle cell trait highlights the importance of neonatal
      screening in the Federal District to support work by health managers and
      professionals for planning educational measures and reducing the morbidity
      associated with sickle cell disease.

PMID- 19180302
TI  - [Support for and resistance to homeopathy among managers of the Unified National
      Health System].
AB  - This article presents partial findings from a study on trends towards greater or
      lesser proximity between homeopathic and allopathic physicians, from the
      perspective of the latter. Forty-eight health professionals were interviewed
      (faculty, managers, and physicians working in the public health system). This
      specific article focused only on the interviews with health system managers. The
      following concepts were used as references: social and scientific field
      (Bourdieu); medical rationalities (Madel Luz); technological arrangements in
      health work (Mendes-Goncalves); and physician's professional identity (Donnangelo
      & Schraiber). According to the findings, support by managers for the presence of
      Homeopathy in the Unified National Health System is related to their perception
      of social demand, defense of patients' right to choose, and the observation that
      it is a medical practice that reclaims the humanist dimension of medicine, thus
      contributing to user satisfaction. The difficulties and resistances identified by
      managers highlight that the lack of information on homeopathic procedures limits
      the possibilities for use of Homeopathy because it leads to insecurity towards
      this area of medicine.

PMID- 19180303
TI  - [Counseling for physical activity as a health education strategy].
AB  - This study analyzes the prevalence of health counseling related to physical
      activity among users of primary health care, and explores the associated
      variables. This cross-sectional study included a random sample of 4,060 adults
      and 4,003 older adults living in areas covered by primary health care in 41
      cities from seven States of South and Northeast Brazil. Prevalence of counseling
      for physical activity was 28.9% (95%CI: 27.3-30.4) for adults and 38.9% (95%CI:
      37.3-40.6) for elders. Prevalence was consistently higher among older adults, in
      the Northeast, and in areas covered by the Family Health Program. Gender,
      socioeconomic status, smoking, sedentary lifestyle, self-reported chronic non
      communicable diseases, and continuous-use medication were also associated with
      the outcome. Counseling for physical activity at community health centers is
      under-promoted, considering individual needs for healthy living. There is a need
      to improve participation by health professionals from different fields to promote
      physical activity and other healthy behaviors.

PMID- 19180304
TI  - [Factor structure and internal consistency of the Self-Reporting Questionnaire
      (SRQ-20) in an urban population].
AB  - This study focused on the psychometric properties of the Self-Reporting
      Questionnaire (SRQ-20) among workers, evaluating internal consistency criteria
      for the components scales and construct validity. Evaluation of the SRQ-20
      performance used data from a cross-sectional study of a representative sample of
      workers from Feira de Santana, Bahia State, Brazil. The construct validity was
      estimated by means of an exploratory factor analysis of tetrachoric correlations
      and multiple correspondence analysis. The Kuder-Richardson formula (KD-20) was
      used to evaluate the instrument's internal consistency. Factor analysis of
      tetrachoric correlations revealed the extraction of four factors. Cumulative
      explanation of variance was 59.6%. Multiple correspondence analysis identified
      categories according to the groupings of variables comprising the questionnaire.
      Overall and standardized internal consistency coefficient was 0.80. The study
      indicated an acceptable performance by the SRQ-20 for evaluating common mental
      disorders, for use in mental health screening in the workplace.

PMID- 19180305
TI  - [Data on mortality from external causes and events of undetermined intent, Parana
      State, Brazil, 1979 to 2005].
AB  - This study analyzed the quality of data from the Mortality Information System
      (SIM) for deaths due to external causes in the State of Parana, Brazil, 1979 to
      2005, focusing on events of undetermined intent. Deaths were grouped in motor
      vehicle accidents, homicides, suicides, and events of undetermined intent, and
      proportional mortality and relative annual variation of rates over the three-year
      period were analyzed. Motor vehicle accidents (more than 30% of the total) were
      the most frequent causes of death throughout the period, and since 1997 homicides
      have become the second most frequent cause. Deaths due to events of undetermined
      intent caused by weapons (firearms or knives) decreased from 4.8% in 1981 to 0.3%
      in 2005. Mortality rates for events of undetermined intent (overall) decreased
      from 14.9 deaths per 100,000 inhabitants in 1979-81 to 2.0 in 2003-05. Annual
      percentage variation was -13.1% from 1980 to 1985, -6% from 1996 to 2000, and 
      11% from 2000 to 2004. The findings show the good quality of SIM data on external
      causes in the State of Parana, allowing analyses with the potential to support
      programs to prevent injuries as well as health promotion measures.

PMID- 19180306
TI  - [On the threshold of the second half-century of Salud Publica de Mexico].

PMID- 19180307
TI  - Social networks and health-related quality of life: a population based study
      among older adults.
AB  - OBJECTIVE: To examine the relationship between components of social networks and
      health-related quality of life (HRQL) in older adults with and without depressive
      symptoms. MATERIAL AND METHODS: Comparative cross-sectional study with data from
      the cohort study 'Integral Study of Depression', carried out in Mexico City
      during 2004. The sample was selected through a multi-stage probability design.
      HRQL was measured with the SF-36. Geriatric Depression Scale (GDS) and the Short
      Anxiety Screening Test (SAST) determined depressive symptoms and anxiety. T-test
      and multiple linear regressions were conducted. RESULTS: Older adults with
      depressive symptoms had the lowest scores in all HRQL scales. A larger network of
      close relatives and friends was associated with better HRQL on several scales.
      Living alone did not significantly affect HRQL level, in either the study or
      comparison group. CONCLUSIONS: A positive association between some components of
      social networks and good HRQL exists even in older adults with depressive
      symptoms.

PMID- 19180308
TI  - [Prevalence and risk factors of high blood pressure in Mexican school children in
      Sabinas Hidalgo].
AB  - OBJECTIVE: To determine the prevalence and associated risk factors of high blood
      pressure (HBP) in school children 6 to 12 years of age with the accepted
      methodology. MATERIAL AND METHODS: Elementary school children were examined
      (n=329). Associations between HBP, body mass index (BMI), age and gender were
      investigated using a cross-sectional study. Blood pressure was measured and the
      95th percentile was used to determine HBP. Comparisons between children with and
      without HBP were made. The crude and X(2) Mantel-Haenszel adjusted odds ratios
      were used as measures of association. RESULTS: Overweight children (BMI >85th
      percentile) and those in the age group 11-12 years were at least four times as
      likely to present with HBP after controlling for confounding factors. CONCLUSION:
      A total of 4.9% of school children had HBP, with a higher prevalence occurring
      among overweight and the older group. The associations found here can be used as
      markers for an increased likelihood of HBP in Mexican children.

PMID- 19180310
TI  - [Universal access, six years results in the Mexico City HIV/AIDS Program].
AB  - OBJECTIVE: To analyze the results of the Free Antiretroviral Medication Program
      of the Mexico City HIV/AIDS Program among the affected population in Mexico City.
      MATERIAL AND METHODS: A retrospective analysis was conducted of medical
      attention, antiretroviral treatment and specialized laboratory results data from
      2001 to 2006 from patients who sought services from the Mexico City HIV/AIDS
      Program. RESULTS: Data from 5 146 patients who were undergoing ARV are presented.
      At the end of the period studied, 74% were current, 12.2% were not found for
      follow-up and 13.9% had died. CONCLUSIONS: During the period evaluated, wider
      coverage was achieved in Mexico City as well as increased efficiency in ARV
      treatment and increased patient survival.

PMID- 19180309
TI  - Maternal MTHFR polymorphisms and risk of spontaneous abortion.
AB  - OBJECTIVE: To asses the association between intake of folate and B vitamins and
      the incidence of spontaneous abortion (SA) according to the maternal
      methylenetetrahydrofolate reductase (MTHFR) polymorphisms (677 C>T and 1298 A>C).
      MATERIAL AND METHODS: We conducted a nested case-control study within a perinatal
      cohort of women recruited in the state of Morelos, Mexico. Twenty-three women
      with SA were compared to 74 women whose pregnancy survived beyond week 20th.
      Intake of folate and B vitamins respectively, was estimated using a validated
      food frequency questionnaire. Maternal MTHFR polymorphisms were determined by PCR
      RFLP and serum homocysteine levels by HPLC. RESULTS: Carriers of MTHFR 677TT and
      1298AC genotypes respectively showed an increased risk of SA (OR 677TT vs.
      CC/CT=5.0; 95% CI: 1.2, 20.9 and OR 1298 AC vs. AA=5.5; 95% CI: 1.1, 26.6).
      CONCLUSIONS: Our results support the role of MTHFR polymorphisms as a risk factor
      for SA, regardless of dietary intake of B vitamins.

PMID- 19180312
TI  - Culture supernatants from V. cholerae O1 El Tor strains isolated from different
      geographic areas induce cell vacuolation and cytotoxicity.
AB  - OBJECTIVE: To investigate whether the HlyA-induced vacuolating effect is produced
      by V. cholerae O1 ElTor strains isolated from different geographic origins,
      including Mexico. MATERIAL AND METHODS: Supernatant-induced haemolysis,
      vacuolating activity and cytotoxicity in Vero cells were recorded. PCR, RFLP
      analysis and molecular cloning were performed. RESULTS: All ElTor strains
      analyzed induced cellular vacuolation. Ribotype 2 strains isolates from the U.S.
      gulf coast yielded the highest titer of vacuolating activity. Eight of nine
      strains were haemolytic, while all strains were PCR positive for the hlyA gene.
      We cloned the hlyA gene from two ElTor strains, a toxigenic (2514-88, ctxAB+) and
      a non-toxigenic Mexican strain (CM 91-3, ctxAB-). Supernatant from those
      recombinant E. coli strains induced haemolysis, cell vacuolation and
      cytotoxicity. RFLP-PCR analysis revealed similarities in the hlyA gene from all
      strains tested. CONCLUSION: The HlyA-induced vacuolating effect is a widespread
      phenotype of epidemic V. cholerae O1 ElTor strains.

PMID- 19180311
TI  - Rapid response to a case of mumps: implications for preventing transmission at a
      medical research facility.
AB  - OBJECTIVE: To prevent transmission among the staff and potentially among the non
      human primate (NHP) colony at the U.S. Naval Medical Research Center Detachment
      in Peru, where an active case of mumps was discovered in a senior laboratory
      technician in Sep 03, 2007. MATERIAL AND METHODS: Subjects at the research
      facility were interviewed and potentially susceptible contacts were tested for
      mumps IgG. RESULTS: In total, 81 out of 106 staff members (76%) had close contact
      with the case. Only 6/81 (7%) had MMR, 33 (41%) reported having had mumps, and 8
      of 45 (18%) of the potentially susceptible individuals did not have immunity (IgG
      > 20.0). All the susceptible, exposed individuals received MMR vaccine. There
      were no secondary cases and access to the NHP colony was restricted. DISCUSSION:
      Immediate and thorough investigation and occupational health response were
      imperative in preventing secondary cases of mumps among humans and NHP.

PMID- 19180314
TI  - [Association between the TaqI polymorphism of the vitamin D receptor gene and
      lepromatous leprosy in a Mexican population sample].
AB  - OBJECTIVE: To establish the association of the vitamin D receptor gene TaqI
      polymorphism with lepromatous leprosy (LL) in individuals from Sinaloa, Mexico.
      MATERIAL AND METHODS: A 740 bp fragment was amplified from the VDR gene in DNA
      samples of 71 patients with LL and 144 controls in the Hospital General de
      Culiacan during 2004-2007. Polymorphism was identified through TaqI endonuclease.
      RESULTS: A significant increase in the genotype TT of the VDR gene was observed
      in patients when compared to controls (p = 0.040; OR = 1.82). CONCLUSIONS: Our
      data support the association between the TT genotype and susceptibility to LL in
      this Mexican population.

PMID- 19180313
TI  - [Technical efficiency in primary care for patients with diabetes].
AB  - OBJECTIVE: To quantify the technical efficiency of diabetes care in family
      practice settings, characterize the provision of services and health results, and
      recognize potential sources of variation. MATERIAL AND METHODS: We used data
      envelopment analysis with inputs and outputs for diabetes care from 47 family
      units within a social security agency in Nuevo Leon. Tobit regression models were
      also used. RESULTS: Seven units were technically efficient in providing services
      and nine in achieving health goals. Only two achieved both outcomes. The
      metropolitan location and the total number of consultations favored efficiency in
      the provision of services regardless of patient attributes; and the age of the
      doctor, the efficiency of health results. CONCLUSIONS: Performance varied within
      and among family units; some were efficient at providing services while others at
      accomplishing health goals. Sources of variation also differed. It is necessary
      to include both outputs in the study of efficiency of diabetes care in family
      practice settings.

PMID- 19180315
TI  - Public health workforce in Latin America and the Caribbean: assessment of
      education and labor in 17 countries.

PMID- 19180316
TI  - Comparative study of the cytotoxic effect of Resilon against two cell lines.
AB  - Resilon is a new material that is a candidate to replace gutta-percha as a root
      filling material. This study evaluated the antiproliferative effect of Resilon
      and two commercially available gutta-percha points (Roeko, Dentsply). Two
      established cell lines (L929 and RPC-C2A) were used for the experiment. Cell
      survival fraction was estimated by the sulforhodamine-B assay, in reference to
      controls after 48-h exposure. Non-parametric tests (Kruskal-Wallis followed by
      Dunn's multiple comparisons) were used to evaluate the statistical significance
      of the results (alpha=0.05). Cytotoxicity in a descending order was: Resilon >
      Roeko gutta-percha > Dentsply gutta-percha. At 24-h exposure, no statistically
      significant differences (p>0.05) were observed between tested materials in both
      cell lines. At 48-h exposure, statistically significant differences (p<0.05) were
      found between Resilon and the other materials in the L929 cell line. In the RPC
      C2A cell line Resilon was significantly more cytotoxic than Dentsply gutta-percha
      (p<0.05), but no statistically significant differences (p>0.05) were found
      between Resilon and Roeko gutta-percha. The cytotoxicity of Resilon increased
      significantly from 24 h to 48 h in both cell lines. Resilon points were more
      cytotoxic than gutta-percha points. The cytotoxicity was time dependent and
      increased after 48 h.

PMID- 19180317
TI  - Quantitative radiographic evaluation of periapical bone resorption in dog's teeth
      contaminated with bacterial endotoxin (LPS) associated or not with calcium
      hydroxide.
AB  - The aim of this study was to quantify radiographically the periapical bone
      resorption in dogs' teeth contaminated with bacterial endotoxin (LPS), associated
      or not with calcium hydroxide. After pulp tissue removal, 60 premolars were
      randomly assigned to 4 groups and were either filled with LPS (group 1), filled
      with LPS plus calcium hydroxide (group 2) or filled with saline (group 3) for a
      period of 30 days. In group 4, periapical lesion formation was induced with no
      canal treatment. Standardized radiographs were taken at the beginning of the
      treatment and after 30 days and the Image J Program was used for measurement of
      periapical lesion size. Periapical lesions were observed in groups 1 (average of
      8.44 mm2) and 4 (average of 3.02 mm2). The lamina dura was intact and there were
      no areas of periapical bone resorption in groups 2 and 3. It may be concluded
      that calcium hydroxide was effective in inactivating LPS, as demonstrated by the
      absence of apical periodontitis in the roots that were filled with bacterial
      endotoxin plus calcium hydroxide.

PMID- 19180318
TI  - In vitro antimicrobial activity of endodontic pastes with propolis extracts and
      calcium hydroxide: a preliminary study.
AB  - The purpose of this study was to evaluate the antimicrobial activity of two
      experimental pastes containing propolis extract associated with calcium hydroxide
      against polymicrobial cultures collected from 16 necrotic and fistulae root
      canals in primary molars of 4-8-year-old children of both sexes. The agar-well
      diffusion technique was used to determine the antimicrobial activity of the
      following pastes: 11.0% ethanolic extract of propolis (EEP) + calcium hydroxide;
      and 11.0% extract of propolis without ethanol (EP) + calcium hydroxide. EEP, EP
      and the association of calcium hydroxide and propylene glycol (CHP) was used as
      the positive control groups, and propylene glycol was used as a negative control
      group. Friedman and Wilcoxon tests were used to compare the data from the
      microbial growth inhibition zones (p<0.05). Paste 1 and Paste 2 showed larger
      growth inhibition zones against microorganisms from root canal samples than CHP
      (p=0.021 and 0.003, respectively). Paste 2 tended to have larger growth
      inhibition zones than Paste 1 (p=0.053). The association between propolis and
      calcium hydroxide was effective in controlling dental infections in vitro.

PMID- 19180319
TI  - Computed tomography assessment of the efficiency of different techniques for
      removal of root canal filling material.
AB  - This study evaluated the efficiency of different techniques for removal of
      filling material from root canals, using computed tomography (CT). Sixty mesial
      roots from extracted human mandibular molars were used. Root canals were filled
      and, after 6 months, the teeth were randomly assigned to 3 groups, according to
      the root-filling removal technique: Group A - hand instrumentation with K-type
      files; Group B - reciprocating instrumentation with engine-driven K-type files;
      and Group C rotary instrumentation with engine-driven ProTaper system. CT scans
      were used to assess the volume of filling material inside the root canals before
      and after the removal procedure. In both moments, the area of filling material
      was outlined by an experienced radiologist and the volume of filling material was
      automatically calculated by the CT software program. Based on the volume of
      initial and residual filling material of each specimen, the percentage of filling
      material removed from the root canals by the different techniques was calculated.
      Data were analyzed statistically by ANOVA and chi-square test for linear trend
      (?=0.05). No statistically significant difference (p=0.36) was found among the
      groups regarding the percent means of removed filling material. The analysis of
      the association between the percentage of filling material removal (high or low)
      and the proposed techniques by chi-square test showed statistically significant
      difference (p=0.015), as most cases in group B (reciprocating technique)
      presented less than 50% of filling material removed (low percent removal). In
      conclusion, none of the techniques evaluated in this study was effective in
      providing complete removal of filling material from the root canals.

PMID- 19180320
TI  - Prevalence of endodontically treated teeth in a Brazilian adult population.
AB  - This cross-sectional study examined the prevalence of endodontically treated
      teeth in 1,401 Brazilian adults. Panoramic radiographs were selected at the
      Radiological Center of Orofacial Images (CRIOF, Cuiaba, MT, Brazil) between
      August 2002 and September 2007. Three independent endodontists discussed
      interpretation criteria and classified specimens according to the following data:
      presence of root canal treatment, which was defined as partially or completely
      filled canal space, regardless of whether filling ended at the radiographic apex
      or not; presence of intracanal post; and associated apical periodontitis. Odds
      ratio, logistic regression and a chi-square test were used for statistical
      analyses. Significance level was set at p<0.05. Of 29,467 teeth evaluated, 6,313
      (21.4%) were treated endodontically. Endodontic treatment was most frequent in
      maxillary premolars and molars, whereas mandibular incisors showed the lowest
      prevalence. Most endodontically treated teeth were found in people aged 46 to 60
      years (47.6%, p<0.001) and the prevalence increased with age in this age range.
      Females (61.9%, p<0.001) showed a higher prevalence of teeth with root fillings
      than males. The present study found a higher prevalence of endodontically treated
      teeth in a Brazilian adult population compared to the prevalence reported in
      epidemiological studies conducted in other countries.

PMID- 19180321
TI  - Arginine and glutamate levels in the gingival crevicular fluid from patients with
      chronic periodontitis.
AB  - The objectives of this study were to determine arginine and glutamate levels in
      the gingival crevicular fluid (GCF) of adult chronic periodontitis patients
      versus periodontally healthy controls, and to compare two kinds of microdialysis
      probes: normal and U-shaped probes. The analysis of GCF components was developed
      to improve the diagnosis of periodontal disease (PD). Proteolysis in the
      periodontal tissues increases the concentration of amino acids (aa) in the GCF
      and the levels of these aa may reveal PD features and stages. GCF samples were
      collected by microdialysis in situ from 5 periodontally affected sites (probing
      depth >or=5 mm, clinical attachment loss >or=3 mm) in 14 adult chronic
      periodontitis patients and from 14 adult periodontally healthy controls.
      Capillary zone electrophoresis coupled to laser induced fluorescence detection
      was used to measure concentration of arginine and glutamate in the GCF. Data were
      analyzed statistically by ANOVA and Tukey's post-hoc tests (a=0.05). Arginine
      concentration was increased (p<0.001) and glutamate concentration was decreased
      (p<0.001) in chronic periodontitis patients as compared to controls. There were
      no significant differences (p=0.069) between the normal and U-shaped probes. In
      conclusion, the increase of arginine and decrease of glutamate concentration in
      GCF were associated to the presence of periodontitis, and might be used as
      markers to recognize periodontally susceptible subjects as well as to evaluate
      the treatment course.

PMID- 19180322
TI  - Short-term effect of COX-2 selective inhibitor as an adjunct for the treatment of
      periodontal disease: a clinical double-blind study in humans.
AB  - Adjunctive therapeutic strategies that modulate the inflammatory mediators can
      play a significant role in periodontal therapy. In this double-blind, placebo
      controlled study, 60 subjects diagnosed as periodontitis patients were evaluated
      for 28 days after periodontal treatment combined with selective cyclooxygenase-2
      (COX-2) inhibitor. The experimental group received scaling and root planning
      (SRP) combined with the Loxoprofen antiinflammatory drug (SRP+Loxoprofen). The
      control group received SRP combined with placebo (SRP+placebo). Plaque index
      (PI), probing pocket depth (PD) and bleeding on probing (BOP) were monitored with
      an electronic probe at baseline and after 14 and 28 days. Both groups displayed
      clinical improvement in PD, PI and BOP. They also showed statistically similar
      values (p>0.05) of PD reduction on day 14 (0.4 mm) and on day 28 (0.6 mm). At the
      baseline, few deeper sites (>or=7 mm) from SRP+Loxoprofen group were responsible
      and most PD reduction was observed after 14 days (p<0.05). The percentage of
      remaining deep pockets (>or=7 mm) after 14 days in the SRP+Loxoprofen group was
      significantly lower (p<0.05) than in the SRP+placebo group. Loxoprofen presents
      potential effect as an adjunct of periodontal disease treatment, but long-term
      clinical trials are necessary to confirm its efficacy.

PMID- 19180323
TI  - Fracture resistance of weakened roots restored with composite resin and glass
      fiber post.
AB  - This study evaluated the fracture resistance of weakened roots restored with
      glass fiber posts, composite resin cores and complete metal crowns. Thirty
      maxillary canines were randomly divided into 3 groups of 10 teeth each: teeth
      without weakened roots (control); teeth with partially weakened roots (PWR) and
      teeth with and largely weakened roots (LWR). The control group was restored with
      glass fiber posts and a composite resin core. Teeth in the PWR and LWR groups
      were flared internally to standardized dimensions in order to simulate root
      weakness. Thereafter, the roots were partially filled with composite resin and
      restored in the same way as in the control group. The specimens were exposed to
      250,000 cycles in a controlled chewing simulator. All intact specimens were
      subjected to a static load (N) in a universal testing machine at 45 degrees to
      the long axis of the tooth until failure. Data were analyzed by one-way ANOVA and
      Dunnett's test for multiple comparisons (p=0.05). There were statistically
      significant difference differences (p<0.01) among the groups (control group =
      566.73 N; PWR = 409.64 N; and LWR = 410.91 N), with significantly higher fracture
      strength for the control group. There was no statistically significant difference
      (p>0.05) between the weakened groups. The results of this study showed that
      thicker root dentin walls significantly increase the fracture resistance of
      endodontically treated teeth.

PMID- 19180324
TI  - Effect of different modes of light modulation on the bond strength and knoop
      hardness of a dental composite.
AB  - This study evaluated the bond strength and Knoop hardness of Z250 composite
      resin, light activated with XL2500 curing unit, using different protocols:
      continuous mode - high intensity (CH) (700 mW/cm(2)) for 20 s; continuous mode -
      low intensity (CL) (150 mW/cm(2)) for 20 s; and pulse-delay with 150 mW/cm(2) for
      2(P2), 3(P3), 5(P5), 10(P10) or 15 s (P15), with a 1-min delay, followed by 700
      mW/cm(2) for 20 s. For the push-out test (n=10), the bond strength values were
      obtained using a universal test machine at a crosshead speed of 0.5 mm/min. For
      Knoop hardness (n=5), the specimens were made using the same light-activation
      protocols. The hardness measurements were made with a hardness tester at six
      depths (top, 1, 2, 3, 4, and 5 mm). The data were subjected to ANOVA and Tukey's
      test at 5% significance level. For bond strength, CL and P5 presented
      significantly higher mean values (p<0.05) than the other groups. There was no
      statistically significant difference (p>0.05) between P2, P3, P10, P15 and CH.
      For Knoop hardness, CH and P15 presented the highest mean values from top surface
      up to 4 mm depth , while CL presented the lowest hardness mean values (p<0.05).
      From the depth of 3 mm to 5 mm, the mean values of all groups were significantly
      lower (p<0.05) than those recorded on top surface. In conclusion, for the pulse
      delay method, the initial exposure time can influence bond strength and Knoop
      hardness of composites.

PMID- 19180325
TI  - Bond strength of a pit-and-fissure sealant associated to etch-and-rinse and self
      etching adhesive systems to saliva-contaminated enamel: individual vs.
      simultaneous light curing.
AB  - This study evaluated in vitro the shear bond strength (SBS) of a resin-based pit
      and-fissure sealant [Fluroshield (F), Dentsply/Caulk] associated with either an
      etch-and-rinse [Adper Single Bond 2 (SB), 3M/ESPE] or a self-etching adhesive
      system [Clearfil S3 Bond (S3), Kuraray Co., Ltd.] to saliva-contaminated enamel,
      comparing two curing protocols: individual light curing of the adhesive system
      and the sealant or simultaneous curing of both materials. Mesial and distal
      enamel surfaces from 45 sound third molars were randomly assigned to 6 groups
      (n=15), according to the bonding technique: I - F was applied to 37% phosphoric
      acid etched enamel. The other groups were contaminated with fresh human saliva
      (0.01 mL; 10 s) after acid etching: II - SB and F were light cured separately;
      III - SB and F were light cured together; IV - S3 and F were light cured
      separately; V - S3 and F were light cured simultaneously; VI - F was applied to
      saliva-contaminated, acid-etched enamel without an intermediate bonding agent
      layer. SBS was tested to failure in a universal testing machine at 0.5 mm/min.
      Data were analyzed by one-way ANOVA and Fisher's test (alpha=0.05).The debonded
      specimens were examined with a stereomicroscope to assess the failure modes.
      Three representative specimens from each group were observed under scanning
      electron microscopy for a qualitative analysis. Mean SBS in MPa were: I-12.28 (+/
      4.29); II-8.57 (+/-3.19); III-7.97 (+/-2.16); IV-12.56 (+/-3.11); V-11.45 (+/
      3.77); and VI-7.47 (+/-1.99). In conclusion, individual or simultaneous curing of
      the intermediate bonding agent layer and the resin sealant did not seem to affect
      bond strength to saliva-contaminated enamel. S3/F presented significantly higher
      SBS than the that of the groups treated with SB etch-and-rinse adhesive system
      and similar SBS to that of the control group, in which the sealant was applied
      under ideal dry, noncontaminated conditions.

PMID- 19180326
TI  - Effect of microwave disinfection on physical and mechanical properties of acrylic
      resins.
AB  - This study evaluated the effect of microwave energy on the hardness, impact
      strength and flexural strength of the Classico, Onda-Cryl and QC-20 acrylic
      resins. Aluminum die were embedded in metallic or plastic flasks with type III
      dental stone, in accordance with the traditional packing technique. A mixing
      powder/liquid ratio was used according to the manufacturer's instructions. After
      polymerization in water batch at 74 degrees C for 9 h, boiling water for 20 min
      or microwave energy at 900 W for 10 min, the specimens were deflasked after flask
      cooling at room temperature, and submitted to finishing. Specimens non
      disinfected and disinfected by microwave irradiation were submitted to hardness,
      impact and flexural strength tests. Each specimen was immersed in distilled water
      and disinfected in a microwave oven calibrated to 650 W for 3 min. Knoop hardness
      test was performed with 25 g load for 10 s, impact test was carried out using the
      Charpy system with 40 kpcm, and 3-point bending test with a crosshead speed of
      0.5 mm/min until fracture. Data were submitted to statistical analysis by ANOVA
      and Tukey's test (alpha=0.05). Disinfection by microwave energy decreased the
      hardness of Classico and Onda-Cryl acrylic resins, but no effect was observed on
      the impact and flexural strength of all tested resins.

PMID- 19180327
TI  - Bite force in temporomandibular dysfunction (TMD) and healthy complete denture
      wearers.
AB  - The signs and symptoms of temporomandibular dysfunction (TMD) may contribute to
      reduce bite force and muscular activity. The aims of this study were to compare
      bite force in complete denture wearers with TMD (TMD group) and without TMD
      (healthy group).The TMD group consisted of 9 individuals, who had worn a
      maxillary and a mandibular complete removable denture for more than 10 years. The
      healthy group consisted of 9 participants who wore dentures and had satisfactory
      interocclusal and maxillomandibular relationship. Helkimo Index was used to
      analyze the dysfunction level. Maximum bite force was measured using a digital
      dynamometer with capacity of 100 kgf and adapted to oral conditions.The TMD group
      presented smaller mean bite force values than the healthy group, though without
      statistical significance (p>0.05). This outcome suggests that the TMD signs and
      symptoms and the structural conditions of the dentures did not affect the maximal
      bite force of complete denture wearers.

PMID- 19180328
TI  - Relation between implant/abutment vertical misfit and torque loss of abutment
      screws.
AB  - This study investigated whether there is a direct correlation between the level
      of vertical misfit at the abutment/implant interface and torque losses (detorque)
      in abutment screws. A work model was obtained from a metal matrix with five 3.75
      x 9 mm external hex implants with standard platform (4.1 mm). Four frameworks
      were waxed using UCLA type abutments and one-piece cast in commercially pure
      titanium. The misfit was analyzed with a comparator microscope after 20 Ncm
      torque. The highest value of misfit observed per abutment was used. The torque
      required to loose the screw was evaluated using a digital torque meter. The
      torque loss values, measured by the torque meter, were assumed as percentage of
      initial torque (100%) given to abutment screws. Pearson's correlation
      (alpha=0.05) between the misfit values (29.08 +/- 8.78 microm) and the percentage
      of detorque (50.71 +/- 11.37%) showed no statistically significant correlation
      (p=0.295). Within the limitations of this study, it may be concluded that great
      vertical misfits dot not necessarily implies in higher detorque values.

PMID- 19180329
TI  - Improvement of XTT assay performance for studies involving Candida albicans
      biofilms.
AB  - 2, 3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H
      tetrazolium hydroxide (XTT) reduction assay has been used to study Candida
      biofilm formation. However, considering that the XTT reduction assay is dependent
      on cell activity, its use for evaluating mature biofilms may lead to inaccuracies
      since biofilm bottom cell layers tend to be relatively quiescent at later stages
      of biofilm formation. The aim of this study was to improve XTT reduction assay by
      adding glucose supplements to the standard XTT formulation. Candida albicans ATCC
      90028 was used to form 24-, 48- and 72-h biofilms. The oxidative activity at 90,
      180 and 270 min of incubation was evaluated. The control consisted of standard
      XTT formulation without glucose supplements, and was modified by the addition of
      50, 100 and 200 mM of glucose. The XTT assay with 200 mM glucose showed more
      accurate and consistent readings correlating with biofilm development at 24, 48
      and 72 h. Biofilm growth yield after 180 min incubation, when evaluated with the
      200 mM glucose supplemented XTT, produced the most consistent readings on
      repetitive testing. It may be concluded that glucose supplementation of XTT could
      minimize variation and produce more accurate data for the XTT assay.

PMID- 19180330
TI  - Evaluation of iris color stability in ocular prosthesis.
AB  - Accurate iris reproduction in the fabrication of ocular prosthesis in order to
      match the remaining eye is a key factor to mask the loss and achieve an esthetic
      outcome for anophthalmic patients. This study evaluated the stability of acrylic
      paints used for replicating iris color in ocular prostheses by the analysis of
      two factors: the temperature of the acrylic resin polymerization cycle during
      prosthesis fabrication and the incidence of sun light, which is the main
      photodegrading agent undermining the longevity of ocular prostheses. An
      accelerated aging assay was used for both analyses. Specimens simulating the
      prosthetic iris in the colors blue, yellow, black, brown and green were
      fabricated, and were submitted to a colorimetric reading before and after
      undergoing the thermal conditions of acrylic resin polymerization. Next, the
      specimens were submitted to an artificial accelerated aging assay with
      ultraviolet radiation A and weekly colorimetric readings during a 3-week period.
      The color change (Delta E*) values for the four specimens painted with the same
      color paint were averaged and the resulting values were considered for
      statistical analysis. Levine's test and Student's t-test were used to analyze the
      influence of the temperature of the polymerization cycle during prosthesis
      fabrication on the color stability of each acrylic resin paint. Friedman's test
      for three dependent samples was used for analysis of color photodegradation as
      function of time. Significance level was set at 0.05 for all analyses. It was
      observed that, after the action of the temperature of the polymerization cycle,
      alteration above clinically acceptable level of Delta E*> 3.3 was observed only
      for the yellow color. After the accelerated aging assay, there were statistically
      significant differences (p<0.05) as a function of time in the green, brown, black
      and blue colors. Changes were clinically acceptable for the brown and black
      colors; slightly above the clinically acceptable limit for the green color; and
      significantly high and impracticable from a clinical standpoint for the blue
      color. There was no statistically significant differences (p>0.05) for the yellow
      color, which presented color change only a little above the clinically acceptable
      limit. IN CONCLUSION: 1. Only the yellow color presented alterations above the
      clinically acceptable levels after the polymerization cycle; 2. After accelerated
      aging, there was no changes in the yellow color above the clinically acceptable
      levels; 3. For the green color, degradation was significant and slightly above
      the clinically acceptable levels; 4. The black, brown and blue colors presented
      significant alterations as function of time; the alterations of the brown and
      black colors were within acceptable clinical levels, while the blue color
      presented a more accentuated degradation over time.

PMID- 19180332
TI  - Respiratory manifestations and esophageal diseases.

PMID- 19180333
TI  - Predictors of adherence to treatment in patients with severe asthma treated at a
      referral center in Bahia, Brazil.
AB  - OBJECTIVE: To determine the rate of adherence to treatment with inhaled
      corticosteroids in patients with severe asthma, to identify predictive factors
      for adherence and to evaluate the relationship between adherence to treatment and
      parameters of clinical and functional response. METHODS: Prospective cohort study
      of patients enrolled in the Program for the Control of Asthma and Allergic
      Rhinitis in the state of Bahia, Brazil. The study comprised 160 patients with
      severe asthma, monitored for 180 days in order to evaluate adherence (dependent
      variable) to the prescribed inhaled corticosteroid. Independent variables were
      assessed at baseline and for a six-month follow-up period by means of interviews
      and the completion of a standardized questionnaire.Patients recorded the missed
      doses in a diary. RESULTS: Of the 160 patients. 158 completed the study.
      Adherence rate was 83.8%. Of the 158 patients, 112 (70.9%) were considered
      adherent (cut-off point: 80% of prescribed doses administered). There was a
      significant association between asthma control and adherence to
      treatment.Predictors of poor adherence were adverse effects, living far from the
      referral center, limited resources to pay for transportation and dose schedule.
      Other factors, such as depressive symptoms, religion and economic status, were
      not associated with poor adherence. CONCLUSIONS: Adherence to asthma treatment
      was high and was associated with the clinical response to treatment, in a sample
      of patients with severe asthma enrolled in a public program that provides free
      medication and the assistance of a multiprofessional specialized team in a
      referral center.

PMID- 19180334
TI  - Influence of pleural drainage on postoperative pain, vital capacity and six
      minute walk test after pulmonary resection.
AB  - OBJECTIVE: To evaluate the influence of pleural drainage on the distance covered
      on the six-minute walk test, pain intensity and vital capacity in patients
      submitted to pulmonary resection. METHODS: Thirteen consecutive patients from the
      Thoracic Surgery Infirmary of Hospital Sao Paulo, Brazil, submitted to closed
      pleural drainage (0.5-in multiperforated chest tube) in the postoperative period
      following pulmonary resection (lobectomy, segmentectomy and pulmonary nodule
      resection) were evaluated. The decision for chest tube removal followed clinical
      criteria defined by the surgical team, who did not participate in the study.
      Vital capacity, pain intensity (using a visual analog pain scale) and the
      distance covered on the six-minute walk test were determined 30 min prior to and
      30 min after the removal of the chest tube. The statistical analysis was
      performed using paired t-tests, and the level of significance was set at 0.05.
      RESULTS: After the removal of the chest tube, the visual analog scale pain scores
      were significantly lower (3.46 cm vs. 1.77 cm; p = 0.001) and the distance
      covered on the six-minute walk test was significantly higher (374.34 m vs. 444.62
      m; p = 0.03). Vital capacity prior to and after chest tube removal was not
      significantly affected (2.15 L and 2.25 L, respectively; p = 0.540). CONCLUSIONS:
      The results of the present study suggest that the presence of a chest tube is a
      factor significantly associated with postoperative pain and functional limitation
      in patients submitted to pulmonary resection.

PMID- 19180335
TI  - Validation of the Modified Pulmonary Functional Status and Dyspnea Questionnaire
      and the Medical Research Council scale for use in Brazilian patients with chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: To determine the validity and reproducibility of two subjective
      instruments to assess limitations in activities of daily living (ADLs) in
      patients with chronic obstructive pulmonary disease (COPD) in Brazil: the
      Pulmonary Functional Status and Dyspnea Questionnaire - Modified version (PFSDQ
      M) and the Medical Research Council (MRC) scale. METHODS: Thirty patients with
      COPD (age, 67 +/- 10 years; males, 17; forced expiratory volume in one second,
      42% +/- 13% of predicted) completed the Portuguese-language versions of the two
      instruments on two occasions, one week apart. The PFSDQ-M has three components:
      influence of dyspnea on ADLs, influence of fatigue on ADLs change in ADLs
      experienced by the patient. The MRC scale is simple, with only five items, in
      which patients report the degree to which dyspnea limits their performance of
      ADLs. The traditional Saint George's Respiratory Questionnaire (SGRQ), previously
      validated for use in Brazil, was used as a validation criterion. RESULTS: The
      test-retest reliability (intraclass correlation coefficient) of the PFSDQ-M was
      0.93, 0.92 and 0.90 for dyspnea, fatigue and change components, respectively,
      compared with 0.83 for the MRC scale. Bland-Altman plots showed good test-retest
      agreement for the PFSDQ-M. The components of the PFSDQ-M and the MRC scale
      correlated significantly with all of the domains and the total score of the SGRQ
      (0.49 < r < 0.80; p < 0.01 for all). CONCLUSIONS: The Portuguese-language
      versions of the PFSDQ-M and the MRC scale proved reproducible and valid for use
      in patients with COPD in Brazil.

PMID- 19180336
TI  - Determination of alpha 1-antitrypsin levels and of the presence of S and Z
      alleles in a population of patients with chronic respiratory symptoms.
AB  - OBJECTIVE: To determine the levels of alpha-1 antitrypsin (AAT) and the presence
      of S and Z alleles in patients with chronic respiratory symptoms. METHODS:
      Patients with chronic cough and dyspnea were submitted to clinical evaluation,
      pulmonary function tests, high-resolution computed tomography, nephelometric
      determination of AAT and determination of S and Z alleles by polymerase chain
      reaction. Smoking and AAT levels were considered the dependent variables.
      RESULTS: Of the 89 patients included in the study, 44 were female. The mean age
      was 51.3 +/- 18.2 years. The S and Z alleles were detected in 33.3% and 5.7%,
      respectively, and the gene frequency was 0.16 and 0.028, respectively. Two
      patients were SZ heterozygotes (AAT levels < 89 mg/dL). The patients were divided
      into groups based on AAT level: < 89 mg/dL (deficiency, no group); 90-140 mg/dL
      (intermediate, Group 1, n = 30); and > 141 mg/dL (normal, Group 2, n = 57). The
      frequency of smokers was the same in both groups, although tobacco intake was
      greater in Group 2. The S allele was present in 13 and 14 patients in Groups 1
      and 2, respectively, whereas the Z allele was present in 2 and 1 patient in the
      same groups. There was no difference in the results of pulmonary function tests
      or in the frequency of bronchiectasis or emphysema between the two groups.
      Spirometric values and AAT levels were similar in smokers and nonsmokers.
      Bronchiectasis was more common in nonsmokers, and emphysema was more common in
      smokers. CONCLUSIONS: Thirty patients presented AAT levels lower than the mean
      values found in patients with the MM or MS genotype, and this fact could not be
      explained by an increased frequency of S and Z alleles.

PMID- 19180337
TI  - Influence of oscillating positive expiratory pressure and the forced expiratory
      technique on sputum cell counts and quantity of induced sputum in patients with
      asthma or chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To evaluate whether respiratory therapy techniques influence the
      number of cells within and quantity of induced sputum in patients with asthma or
      chronic obstructive pulmonary disease (COPD). METHODS: Randomized clinical trial,
      in which patients with asthma or COPD under intervention (n = 16 and 10,
      respectively) were compared with control groups (n = 16 and 10). Patients in the
      asthma/intervention (A/I) and COPD/intervention (C/I) groups were submitted to
      oscillating positive expiratory pressure maneuvers for 5 min, followed by 10
      forced expiratory technique sequences. These patients were also submitted to an
      induced sputum protocol with inhaled hypertonic saline (3%, 4% or 5%; A/I group)
      or inhaled isotonic saline (C/I group). The asthma/control (A/C) and COPD/control
      (C/C) groups were submitted only to the standard induced sputum protocol.
      RESULTS: The final mean weight of the sputum samples was significantly greater in
      the A/I group than in the A/C group (2,767.25 +/- 998.08 mg vs. 1,689.17 +/-
      1,189.96 mg; p = 0.03). The mean/median total cell counts (x10(6)/mL) were higher
      in the A/I and C/I groups than in the A/C and C/C groups (4.06/0.95 and
      0.63/0.39, p = 0.05, vs. 5.08/1.77 and 0.64/0.40, p = 0.02). There were no
      statistically significant differences among the groups in terms of cell
      viability. CONCLUSIONS: The use of respiratory therapy techniques can increase
      sputum sample weight in asthma patients, as well as increasing total cell counts
      in patients with asthma or COPD.

PMID- 19180338
TI  - Laboratorial validation of an automated assay for the determination of adenosine
      deaminase activity in pleural fluid and cerebrospinal fluid.
AB  - OBJECTIVE: The incidence of tuberculosis worldwide has emphasized the need for
      better assays designed to diagnose the disease, principally the extrapulmonary
      form. The objective of the present study was to validate the performance of an
      automated method for the determination of adenosine deaminase (ADA) activity in
      pleural fluid (PF) and cerebrospinal fluid (CSF), comparing it with a
      conventional method (the modified Giusti method). METHODS: In total, 134 samples
      were selected from among those tested in our laboratory: 94 PF samples and 40 CSF
      samples. The ADA activity was determined using the two methods. Inter- and intra
      assay precision was determined, linear regression analysis was performed, simple
      concordance tests were conducted, and the means of the differences were
      calculated. RESULTS: The correlation coefficients for PF and CSF samples were,
      respectively, 0.96 and 0.95. Inter-assay precision was determined using 21
      replicates at 3 different activity levels: low, medium and high. The percentage
      coefficient of variation (%CV) was, respectively, 5.9, 8.1 and 5.8 for PF
      samples, compared with 21.9, 18.6 and 13.8 for CSF samples. Intra-assay precision
      in %CV was 1.3 and 11.7, respectively, for PF and CSF samples. The concordance
      between the methods in PF and CRF samples was, respectively, 96.8% and 100%,
      considering the reference values for the diagnosis of TB to be 40 U/L
      (conventional) and 30 U/L (automated) in PF samples, versus 9 U/L (for both
      methods) in CSF samples. CONCLUSIONS: The results validate the use of the
      automated method of determining ADA activity in PF and CSF samples as an
      alternative to the conventional method.

PMID- 19180339
TI  - Esophageal manometry and 24-h esophageal pH-metry in a large sample of patients
      with respiratory symptoms.
AB  - OBJECTIVE: To determine the prevalence of gastroesophageal reflux disease (GERD)
      and to evaluate the esophageal motor profile of patients with respiratory
      symptoms referred to a digestive motility referral center for esophageal function
      testing. METHODS: The results of esophageal manometry and 24-h esophageal pH
      metry were analyzed.The inclusion criterion was presenting respiratory symptoms,
      with or without accompanying digestive symptoms. RESULTS: Of the 1,170 patients
      included in the study, 602 (51.5%) reported having digestive and respiratory
      symptoms (DRS group), and 568 (48.5%) reported having only respiratory symptoms
      (RS group). Asthma was diagnosed in 142 patients in the RS group (RS-A subgroup)
      and in 201 of those in the DRS group (DRS-A). Of the 346 cases of esophageal
      dysmotility, hypomotility was found in 175 (14.3% and 15.6% in the DRS and RS
      groups, respectively), and lower esophageal sphincter (LES) hypotonia was found
      in 411 (40.3% and 30.2%, respectively). Hypotonia correlated with GERD. Exposure
      of the distal esophagus to acid was markedly abnormal in the supine position. The
      prevalence of GERD in the sample as a whole, the RS-A/DRS-A subgroups and the RS
      A subgroup alone was 39.8%, 44.0% and 35.2%, respectively CONCLUSIONS: Hypotonic
      LES was the most common abnormality and correlated with GERD. Although GERD was
      more evident in the DRS group, approximately one third of the patients in the RS
      group also presented GERD (silent GERD). The findings suggest that GERD can be an
      extrapulmonary cause of chronic respiratory symptoms unresponsive to conventional
      therapy.

PMID- 19180340
TI  - Adverse effects of tuberculosis treatment: experience at an outpatient clinic of
      a teaching hospital in the city of Sao Paulo, Brazil.
AB  - OBJECTIVES: To determine the frequency of adverse effects related to the use of
      the tuberculosis treatment regimen designated Regimen I and the need for regimen
      alterations due to these effects. METHODS: A retrospective analysis of 329
      medical charts of patients who were treated with Regimen I and discharged after
      cure between March 2000 and April 2006 was carried out at the Tuberculosis
      Outpatient Clinic, Department of Pulmonology of the Santa Casa de Misericordia de
      Sao Paulo Hospital in the city of Sao Paulo, Brazil. Adverse effects and the
      timing of their appearance, as well as subsequent modifications in the treatment
      regimen, were investigated. RESULTS: We included 297 patients, 146 (49.1%) of
      whom presented one or more adverse effects related to antituberculosis
      medications. The frequency of minor side effects was 41.1%, and that of major
      side effects was 12.8%. The most common reactions were those involving the
      gastrointestinal tract (40.3%) and the skin (22.1%). Adverse effects were more
      common in the first and second months of treatment (58.4%). Modification of the
      treatment regimen was necessary in 11 cases (3.7% of the total sample). Drug
      induced hepatitis was the adverse effect that demanded the most regimen changes.
      CONCLUSIONS: In this group of patients, the frequency of adverse effects related
      to treatment with Regimen I was 49.1%. However, in most of the cases, it was not
      necessary to modify the treatment regimen due to side effects.

PMID- 19180341
TI  - Conventional and molecular techniques in the diagnosis of pulmonary tuberculosis:
      a comparative study.
AB  - OBJECTIVE: To compare four laboratory methods in the diagnosis of pulmonary
      tuberculosis. METHODS: Respiratory secretion specimens were collected from 160
      patients suspected of having pulmonary tuberculosis. Direct testing for
      Mycobacterium tuberculosis was carried out using Ziehl-Neelsen and auramine
      staining. In addition, culture in Lowenstein-Jensen (LJ) medium and polymerase
      chain reaction (PCR) were used. The strains isolated were identified by means of
      a radiometric method using p-nitro-alpha-acetylamino-beta-hydroxypropiophenone
      (NAP) and classical methods. The sensitivity of the methods was compared to the
      gold standard for the diagnosis of pulmonary tuberculosis, based on clinical,
      radiological and microbiological criteria. RESULTS: Of the 160 patients, 142 were
      diagnosed with pulmonary tuberculosis according to the gold standard. The
      sensitivity of Ziehl-Neelsen staining, auramine staining, culture in LJ medium
      and PCR was 54.2%, 58.4%, 67.6% and 77.5%, respectively, when compared with the
      diagnostic criterion adopted. All four methods presented 100% specificity. In the
      identification of mycobacteria, there was high (96.8%) concordance between PCR
      and the radiometric method using NAP. The sensitivity of PCR was 50.8% in samples
      with negative sputum smear microscopy results and 98.8% in those with positive
      results. The sensitivity of PCR was lower in specimens with negative results in
      sputum smear microscopy and culture than in those with positive results (25.6%
      and 99.0%, respectively). CONCLUSIONS: We found PCR to be a promising method for
      the diagnosis of pulmonary tuberculosis, even in paucibacillary specimens.
      Simultaneous identification and faster results are additional advantages of this
      method.

PMID- 19180342
TI  - Molecular diversity of Mycobacterium tuberculosis strains in a slum area of Rio
      de Janeiro, Brazil.
AB  - This retrospective molecular study involving restriction fragment length
      polymorphism, using insertion sequence 6110 as a marker, was conducted in order
      to provide an initial insight into the genetic diversity of Mycobacterium
      tuberculosis strains isolated in the slums of the Complexo de Manguinhos, located
      in the city of Rio de Janeiro, Brazil. Of the 67 strains evaluated, 23 (34.3%)
      were found to belong to clusters (total clusters, 10). Household and social
      chains of transmission were associated with clustering, in 20% and 60%,
      respectively. Living in the Conjunto Habitacional Programado 2 slum was
      associated with clustering. Although not significant, it is relevant that 26% of
      the clustered strains presented primary resistance. These findings, although
      possibly underestimating the prevalence due to the failure to analyze all
      strains, could help improve the local tuberculosis control program.

PMID- 19180343
TI  - Noncigarette forms of tobacco use.
AB  - There are many preparations for tobacco use, which can be classified as smoking
      or smokeless tobacco. Among the noncigarette preparations that produce smoke, we
      cite cigars, pipes and narghiles. Smokeless tobacco can be found in preparations
      for chewing or for being absorbed by nasal and oral mucosae (snuff). However, all
      tobacco products deliver nicotine to the central nervous system and there is a
      confirmed risk of dependence. In addition, there is no safe form of tobacco use,
      and tobacco users have a significantly increased risk of morbidity and premature
      mortality due to tobacco-related diseases.

PMID- 19180344
TI  - Kikuchi-Fujimoto disease.
AB  - Kikuchi-Fujimoto disease is characterized by fever and lymphadenopathy, usually
      localized in the cervical region. This disease principally affects young females.
      It can be confused with lymphoma, adenocarcinoma metastasis and tuberculosis. We
      report two cases of Kikuchi-Fujimoto disease. In the first case, a 28-year-old
      female had been treated for tuberculosis one year prior and presented with a
      clinical and histological profile compatible with Kikuchi-Fujimoto disease. The
      second patient, a 58-year-old female, initially received treatment for Wegener's
      granulomatosis and, subsequently, for tuberculosis. Histopathological examination
      followed by immunohistochemical analysis confirmed the diagnosis of Kikuchi
      Fujimoto disease in both cases. After the definitive diagnosis had been made,
      both patients were treated symptomatically, and both presented clinical
      improvement within one month. Subsequently, the latter patient developed systemic
      lupus erythematosus.

PMID- 19180345
TI  - Septic pulmonary embolism secondary to jugular thrombophlebitis: a case of
      Lemierre's syndrome.
AB  - Lemierre's syndrome is characterized by acute oropharyngeal infection,
      complicated by internal jugular venous thrombosis secondary to septic
      thrombophlebitis, and by metastatic infections in various distant organs-most
      commonly in the lungs. We report a case of Lemierre's syndrome in a 56-year-old
      female who presented with right-sided neck mass and fever. Right internal jugular
      venous thrombosis was demonstrated on an ultrasound. A computed tomography scan
      of the chest revealed multiple opacities throughout both lungs. An open surgical
      biopsy was performed due to suspicion of pulmonary metastases.
      Anatomopathological examination revealed septic emboli in lung parenchyma.
      Retrospectively, the patient reported a history of pharyngitis two weeks prior to
      hospitalization. After the diagnosis had been made, the patient was treated with
      broad-spectrum antibiotics (cefuroxime for 7 days and azithromycin for 5 days;
      subsequently, because fever persisted, cefepime for 7 days). One month later, a
      computed tomography scan of the chest revealed resolution of the opacities.

PMID- 19180346
TI  - Laryngotracheobronchial papillomatosis: findings on computed tomography scans of
      the chest.
AB  - OBJECTIVE: To present the findings of computed tomography (CT) scans of the chest
      in patients with laryngotracheobronchial papillomatosis. METHODS: We
      retrospectively analyzed CT scans of eight patients, five males and three
      females, ranging from 5 to 18 years of age with a mean age of 10.5 years. Images
      were independently reviewed by two radiologists. In discrepant cases, a consensus
      was reached. RESULTS: The most common CT findings were intratracheal polypoid
      lesions and pulmonary nodules, many of which were cavitated. CONCLUSIONS: In
      patients with laryngotracheobronchial papillomatosis, the most common tomographic
      finding was the combination of intratracheal polypoid lesions and multiple
      pulmonary nodules, many of which were cavitated.

PMID- 19180348
TI  - Microbial transformation of bufotalin by Alternaria alternata AS 3.4578.
AB  - The microbial transformation of a cytotoxic bufadienolide, bufotalin (1), was
      carried out. Three transformed products from 1 by Alternaria alternata were
      isolated. Their structures were characterized as 3-keto-bufotalin (2), 12 beta
      hydroxyl-bufotalin (3), and 3-keto-12 beta-hydroxyl-bufotalin (4) based on the
      extensive NMR studies. Among them, 3 and 4 were new compounds with strong in
      vitro cytotoxic activities against HeLa cells.

PMID- 19180349
TI  - The cognitive profile of amyotrophic lateral sclerosis: A meta-analysis.
AB  - We aimed to clarify the profile of cognitive impairment in ALS, by meta-analysis
      of published studies. Criteria for inclusion were: ALS diagnosed according to El
      Escorial criteria; control group matched for age and education; correction for
      bias due to motor impairment or dysarthria; no dementia in patients and controls.
      Effect sizes reflecting a difference in neuropsychological performance between
      ALS patients and controls were calculated for 12 cognitive domains. The effect of
      demographic and clinical variables (age, disease duration, site of onset) on
      cognition was assessed in a moderator analysis. Of 48 eligible articles, 16
      studies encompassing 554 ALS patients were included. Significant effect sizes
      were found for the Mini Mental State Examination (d=0.8), immediate verbal memory
      (d=0.5), visual memory (d=0.4), fluency (d=0.5), psychomotor speed (d=0.7),
      language (d=0.5) and executive functioning (d=0.3). The results of the latter
      three domains are less reliable due to the possibility of publication bias.
      Psychomotor speed, and to a lesser extent fluency, may have been influenced by
      motor impairment, despite attempts to correct for motor slowness. In conclusion,
      the diversity of cognitive problems in ALS seems greater than was previously
      thought. ALS patients may suffer from cognitive impairment in multiple domains,
      including memory dysfunction.

PMID- 19180351
TI  - Nanoscale structures and mechanics of barnacle cement.
AB  - Polymerized barnacle glue was studied by atomic force microscopy (AFM), scanning
      electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and
      chemical staining. Nanoscale structures exhibiting rod-shaped, globular and
      irregularly-shaped morphologies were observed in the bulk cement of the barnacle
      Amphibalanus amphitrite (=Balanus amphitrite) by AFM. SEM coupled with energy
      dispersive X-ray (EDX) provided chemical composition information, making evident
      the organic nature of the rod-shaped nanoscale structures. FTIR spectroscopy gave
      signatures of beta-sheet and random coil conformations. The mechanical properties
      of these nanoscale structures were also probed using force spectroscopy and
      indentation with AFM. Indentation data yielded higher elastic moduli for the rod
      shaped structures when compared with the other structures in the bulk cement.
      Single molecule AFM force-extension curves on the matrix of the bulk cement often
      exhibited a periodic sawtooth-like profile, observed in both the extend and
      retract portions of the force curve. Rod-shaped structures stained with amyloid
      protein-selective dyes (Congo red and thioflavin-T) revealed that about 5% of the
      bulk cement were amyloids. A dominant 100 kDa cement protein was found to be
      mechanically agile, using repeating hydrophobic structures that apparently
      associate within the same protein or with neighbors, creating toughness on the 1
      100 nm length scale.

PMID- 19180352
TI  - Shallow moving structures promote marine invader dominance.
AB  - Global increases in urban development have resulted in severe habitat
      modification in many estuaries. Most are now dominated by artificial structures,
      which might have a myriad of effects on native species. The provision of extra
      hard substrata presents additional free space, and recent research suggests non
      indigenous epifauna may be able to exploit these artificial structures
      (particularly pontoons) more effectively than native species. The early
      development of fouling assemblages was compared on settlement plates attached to
      fixed or moving experimental structures at depths of 0.5 m and 2 m. Invertebrate
      invaders as a group were disproportionately more numerous on shallow, moving
      plates (essentially floating surfaces) than on deeper plates, whereas native
      epifauna were less numerous than invaders in all treatments. Importantly,
      however, individual invasive species showed differing effects of movement and
      depth. Future management strategies should take into account the potential for
      shallow, moving structures to enhance invader dominance and strongly consider
      using fixed structures to reduce opportunities for invaders.

PMID- 19180353
TI  - Dose requirements for UVC disinfection of catheter biofilms.
AB  - Bacterial biofilms on permanent catheters are the major sources of infection.
      Exposure to ultraviolet-C (UVC) light has been proposed as a method for
      disinfecting the inner surface of catheters. Specification of a UVC-based device
      for in vivo disinfection is based on the knowledge of the required doses to kill
      catheter biofilm. Given these doses and the power of available UVC light sources,
      calculation of the necessary treatment times is then possible. To determine the
      required doses, contaminated urinary catheters were used as test samples and UVC
      treated in vitro. Patient catheters (n = 67) were collected and cut into segments
      of equal size and treated with various UVC doses. After treatment, the biofilm
      was removed by scraping and quantified by counting colony forming units.
      Percentage killing rates were determined by calculating ratios between UVC
      treated samples and controls (no UVC treatment). Mean killing rates were 89.6%
      (0.5 min), 98% (2 min), and 99% (60 min). Approximately 99% killing was obtained
      with a UVC dose of 15 kJ m(-2). This dose, which is about 100 to 1000 times
      greater than the lethal dose for planktonic cells, is expected to be the maximum
      dose required to maintain newly inserted catheters free of contamination. The
      combination of high doses required to kill mature biofilm and the limited effect
      of current UVC light sources result in a relative long treatment time (
      approximately 60 min). If a UVC-based method is to be of practical use for
      disinfection of catheters in the clinic, repeated preventive treatments should be
      carried out on newly inserted catheters.

PMID- 19180354
TI  - A comparative study on BMP-induced osteoclastogenesis and osteoblastogenesis in
      primary cultures of adult rat bone marrow cells.
AB  - Bone remodeling is a process consisting of bone formation and resorption. The
      present study compared the relative osteoclastic and osteoblastic potency of bone
      morphogenetic proteins (BMP)-2, -4, -5, -6, and -7 in primary murine bone marrow
      cultures. All five BMPs stimulated, to varying degree, formation of tartrate
      resistant acid phosphatase (TRAP)-positive multinucleated cells in a time- and
      protein concentration-dependent manner. The TRAP staining intensity correlated
      positively with the number of nuclei per TRAP-positive cell and the mRNA levels
      of colony-stimulating factor (CSF-1), receptor activator of nuclear factor kappaB
      ligand (RANKL), TRAP, and cathepsin K. Under osteogenic conditions, all five BMPs
      stimulated AP activity and mineralized bone nodule formation in a protein
      concentration-dependent manner in the same primary murine bone marrow cell
      culture system. These findings should be useful in designing treatment strategies
      for bone regeneration.

PMID- 19180355
TI  - Bone tissue content of TGF-beta2 changes with time in human heterotopic
      ossification after total hip arthroplasty.
AB  - Transforming growth factor beta isoforms (TGF-beta(1), TGF-beta(2), and TGF
      beta(3)) most likely play a role in bone physiology, but little is known about
      their relative importance in normal as well as in heterotopic bone. This study
      focused on possible differences in the localization and relative content of
      different TGF beta isoforms in heterotopic ossifications (HO) by comparing HOs,
      which have developed less than 17 months (immature HOs) with those developed 3-9
      years (mature HOs). The HOs were harvested after total hip arthroplasty (THA)
      during revision surgery. The HO samples were decalcified, embedded in paraffin
      and sectioned. Azan staining was used to evaluate histological structure of the
      ossifications and immunohistochemical analysis was performed to estimate the
      localization of three TGF beta isoforms in the HOs. Comparison of different TGF
      beta isoforms in the immature and the mature ossifications showed that the
      content of TGF-beta(2) was decreased by almost three times in the mature HO as
      compared to the immature HO (p = 0.0064). The proportions of other isoforms in
      HOs did not differ significantly. This study shows that the relative importance
      of TGF betas change with HO development.

PMID- 19180356
TI  - A pilot trial comparing the availability of vitamins C, B6, and B12 from a
      vitamin-fortified water and food source in humans.
AB  - PRIMARY OBJECTIVE: In a cross-over randomized pilot study, the relative
      absorption of vitamins C, B(6) and B(12) were tested using a commercial vitamin
      water (VW) and a standardized mixed meal (MM). METHODS AND PROCEDURES: Twelve
      adults (22.9+/-3.7 years), received the VW and the MM, randomly ordered, with a
      minimum 7-day washout period between. Blood was drawn pre-ingestion and over a
      post-ingestion period of 300+ min. Test meal quantities were formulated to
      contain equal amounts of vitamins B(6), B(12), and C as per the water label.
      Analysis revealed that a scaling factor had to be used to balance the actual
      content differences between test products. MAIN OUTCOMES AND RESULTS: Using the
      adjusted numbers for actual water vitamin concentration, there were no
      differences in the maximum concentration and the 5-h area under the curve for
      vitamins B(6), B(12) or C between the VW and the MM. CONCLUSIONS: VW was found to
      provide similar in vivo nutrition as the test MM at a caloric saving.

PMID- 19180357
TI  - The influence of selected demographic and lifestyle factors on lutein intakes by
      groups of Polish women.
AB  - The aim of the study was to assess the influence of selected demographic and
      lifestyle factors on the intake of lutein by groups of Polish women aged 19-81
      years. The study was carried out in 100 respondents in the year 2006 with the use
      of 4-day dietary food records. The mean intake of lutein was 2.16 mg/person/day.
      The primary sources of lutein in food rations of the participants were vegetables
      and vegetable products (72.2%), especially leafy vegetables (48.6%), cereal
      products (9.3%) and eggs (7.9%). The main determinants of lutein intake in the
      groups of Polish women were age (r=0.238, P=0.017), body mass index (r=0.250,
      P=0.012), place of dwelling (r=0.206, P=0.050) as well as occupation (r= - 0.249,
      P=0.013). The knowledge of environmental factors affecting lutein consumption is
      important because of its role in the prevention of diet-related diseases.

PMID- 19180358
TI  - Acute effects of low insulinemic sweeteners on postprandial insulin and glucose
      concentrations in obese men.
AB  - OBJECTIVE: This randomized, double-blind, crossover study was designed to assess
      the effects of trehalose, a non-reducing disaccharide, alone and in combination
      with fructose, on postprandial serum insulin and glucose levels in obese men
      compared with a glucose control. METHODS: Participants (n=21) ingested one of
      three study beverages, providing 75 g total carbohydrate, at each test visit, and
      venous blood samples were collected immediately prior to consumption (0 min) and
      at 30 min, 45 min, 60 min, 90 min, and 120 min post-consumption for assessment of
      serum insulin and plasma glucose levels. RESULTS: Consumption of beverages
      containing trehalose and the trehalose/fructose combination blunted glycemic and
      insulinemic incremental areas under the curve by 20-35%, as compared with the
      glucose control. CONCLUSIONS: Trehalose, alone or in combination with fructose,
      elicited lower glycemic and insulinemic responses in obese men as compared with
      glucose alone, and may have advantages in the development of food products.

PMID- 19180360
TI  - Dose-response relationships of three amphotericin B formulations in a non
      neutropenic murine model of invasive aspergillosis.
AB  - New lipid-associated formulations of amphotericin B (AmB) have been developed in
      order to reduce toxicity and enhance the efficacy of AmB by allowing
      administration of higher doses of the drug. We determined the in vivo dose
      response relationships of 1 day and 7 day treatment of AmB, Ambisome (AmBi) and
      Abelcet (ABLC) in a non-neutropenic murine model of invasive aspergillosis by
      using survival as an endpoint. Female CD-1 mice were infected intravenously 48 h
      prior to start therapy with Aspergillus fumigatus (1 x 10(7) conidia/mouse).
      Groups of 10 mice were treated iv for 1 day or 7 days with increasing 2-fold
      doses of AmB, ABLC and AmBi up to a maximum of 20 mg/kg/day. Mortality was
      determined twice daily until day 15. Results were analyzed using product-moment
      survival analysis and by determining the dose response relationships on day 15.
      Survival at day 15 of mice with 7 day AmBi or ABLC treatment was significantly
      better than that of controls or AmB. The ED50s of AmBi and ABLC were 0.06 (95%
      CI: 0.03-0.127) mg/kg and 0.21 (0.06-0.66) mg/kg respectively. In addition, the
      maximum effect was higher for AmBi than ABLC, 90% survival versus 68%,
      respectively. Most of the effects of treatment with AmBi were reached after 1 day
      of treatment, indicating that the first dose given is most important in
      predicting survival. This study shows that AmBi and ABLC were significantly more
      efficacious than AmB in a non-neutropenic murine model of invasive aspergillosis,
      and that the effect observed was primarily dependent on the first dose
      administered.

PMID- 19180361
TI  - Morphology modifications in negatively charged lipid monolayers upon
      mitochondrial creatine kinase binding.
AB  - Mitochondrial creatine kinase (mtCK) may participate to membrane organization at
      the mitochondrial level by modulating lipid state and fluidity. The effect of the
      protein on lipid phase behaviour of different acyl chain length
      phosphatidylglycerol monolayers was analyzed from pressure-area isotherms and
      from the compressional modulus variation with respect to the surface pressure.
      Monolayer morphology was visualized by Brewster angle microscopy. No condensation
      effect was visible on dimyristoylphosphatidylglycerol (DMPG). For the other PG
      monolayers tested, dipalmitoylphosphatidylglycerol (DPPG) and
      distearoylphosphatidylglycerol (DSPG), mtCK facilitated the formation of a liquid
      condensed phase. The effect depended on the surface pressure at which transition
      phase occurred. The effect of mtCK was more pronounced for
      tetramyristoylcardiolipin (TMCL) monolayers, as liquid condensed regions appeared
      10 mN/m below the transition phase of the pure TMCL monolayer. The observed
      domains were circular and rather uniform, indicating a stabilization of the
      condensed phase. The same effect, namely an overall condensation of the monolayer
      with formation of circular domains, was observed upon protein injection beneath
      TMCL monolayers in different condensation states at constant area. MtCK ability
      to induce and stabilize a LC phase on monolayers could have important
      consequences in membrane organization and emphasize its structural role at
      mitochondrial level.

PMID- 19180359
TI  - Tolerance in Drosophila.
AB  - The set of genes that underlie ethanol tolerance (inducible resistance) are
      likely to overlap with the set of genes responsible for ethanol addiction.
      Whereas addiction is difficult to recognize in simple model systems, behavioral
      tolerance is readily identifiable and can be induced in large populations of
      animals. Thus, tolerance lends itself to analysis in model systems with powerful
      genetics. Drosophila melanogaster has been used by a variety of laboratories for
      the identification of genes that interfere with the acquisition of ethanol
      tolerance. Here, I discuss the genes identified as being important for the
      production of ethanol tolerance in Drosophila. Some of these genes have also been
      shown to be important for the production of tolerance in mammals, demonstrating
      that gene discovery in Drosophila has predictive value for understanding the
      molecular pathways that generate tolerance in mammals.

PMID- 19180362
TI  - Is scanning in probed order recall articulatory?
AB  - We consider how theories of serial recall might apply to other short-term memory
      tasks involving recall of order. In particular, we consider the possibility that
      when participants are cued to recall an item at an arbitrary position in a
      sequence, they covertly serially recall the list up to the cued position. One
      question is whether such "scanning" is articulatory in nature. Two experiments
      are presented in which the syllabic length of words preceding and following
      target positions were manipulated, to test the prediction of an articulatory
      based mechanism that time to recall an item at a particular position will depend
      on the number of preceding long words. Although latency was dependent on target
      position, no word length effects on latency were observed. Additionally, the
      effects of word length on accuracy replicate recent demonstrations in serial
      recall that recall accuracy is dependent on the word length of all list items,
      not just that of target items, in line with distinctiveness assumptions. It is
      concluded that if scanning does occur, it is not carried out by covert or overt
      articulation.

PMID- 19180363
TI  - Acquired hedonic and sensory characteristics of odours: influence of sweet liker
      and propylthiouracil taster status.
AB  - Repeated pairings of novel food-related odours with sweet tastes can result in
      enduring changes in sweetness of the odour alone, but have less consistent
      effects on odour liking. Variation in ability to taste propylthiouracil (PROP)
      might account for this, since PROP supertasters (ST) have been reported both to
      experience stronger sweetness intensity and to be more likely to dislike
      sweetness than do PROP nontasters (NT). Alternatively, individual differences in
      liking for sweetness may transfer to sweet-paired odours independently of PROP
      sensitivity. To explore this, evaluations of sucrose, saccharin, and PROP
      solutions were used to classify 92 volunteers as either sweet likers or dislikers
      and as PROP ST, NT, or medium tasters (MT). Changes in pleasantness of odours
      that had been paired with the taste of saccharin increased in sweet likers but
      decreased in dislikers. Odour sweetness increased regardless of PROP taster or
      sweet liker status. PROP ST rated saccharin as more bitter than did other taster
      groups and also showed greater increases in acquired bitterness of the saccharin
      paired odour. Overall, these data suggest that individual differences in
      evaluation of saccharin reliably predict subsequent changes in evaluation of
      saccharin-paired odours, with hedonic changes corresponding with liking for sweet
      tastes and sensory changes reflecting differences in sensory quality between PROP
      taster groups.

PMID- 19180364
TI  - Flanker and Simon effects interact at the response selection stage.
AB  - The present study aimed at investigating the processing stage underlying stimulus
      stimulus (S-S) congruency effects by examining the relation of a particular type
      of congruency effect (i.e., the flanker effect) with a stimulus-response (S-R)
      spatial correspondence effect (i.e., the Simon effect). Experiment 1 used a
      unilateral flanker task in which the flanker also acted as a Simon-like accessory
      stimulus. Results showed a significant S-S Congruency x S-R Correspondence
      interaction: An advantage for flanker-response spatially corresponding trials was
      observed in target-flanker congruent conditions, whereas, in incongruent
      conditions, there was a noncorresponding trials' advantage. The analysis of the
      temporal trend of the correspondence effects ruled out a temporal-overlap account
      for the observed interaction. Moreover, results of Experiment 2, in which the
      flanker did not belong to the target set, demonstrated that this interaction
      cannot be attributed to perceptual grouping of the target-flanker pairs and
      referential coding of the target with respect to the flanker in the congruent and
      incongruent conditions, respectively. Taken together, these findings are
      consistent with a response selection account of congruency effects: Both the
      position and the task-related attribute of the flanker would activate the
      associated responses. In noncorresponding-congruent trials and corresponding
      incongruent trials, this would cause a conflict at the response selection stage. 

PMID- 19180365
TI  - Preoperative staging and treatment options in T1 rectal adenocarcinoma.
AB  - BACKGROUND: Major rectal resection for T1 rectal cancer offers more than 95%
      cancer specific five-year survival to patients surviving the first 30 days after
      surgery. A significant further improvement by development of the surgical
      technique may not be possible. Improvements in the total survival rate have to
      come from a more differentiated treatment modality, taking patient and procedure
      related risk factors into account. Subgroups of patients have operative mortality
      risks of 10% or more. Operative complications and long-term side effects after
      rectum resection are frequent and often severe. RESULTS: Local treatment of T1
      cancers combined with close follow-up, early salvage surgery or later radical
      resection of local recurrences or with chemo-radiation may lead to fewer severe
      complications and comparable, or even better, long-term survival. Accurate
      preoperative staging and careful selection of patients for local or non-operative
      treatment are mandatory. As preoperative staging, at present, is not sufficiently
      accurate, strategies for completion, salvage or rescue surgery is important, and
      must be accepted by the patient before local treatment for cure is initiated.
      RECOMMENDATIONS: It is recommended that polyps with low-risk T1 cancers should be
      treated with endoscopic snare resection in case of Haggitt's stage 1 or 2. TEM is
      recommended if resection margins are uncertain after snare resection for
      Haggitt's stage 3 and 4, and for sessile and flat, low-risk T1 cancers. Average
      risk patients with high-risk T1 cancers should be offered rectum resection, but
      old and comorbid patients with high-risk T1 cancers should be treated
      individually according to objective criteria as age, physical performance as well
      as patient's preference. All patients treated for cure with local resection or
      non-surgical methods should be followed closely.

PMID- 19180367
TI  - 21st Century opportunities in health: E-healthand technology.

PMID- 19180368
TI  - Four concepts of health in America: results of national surveys.
AB  - Our objective was to determine how large, random samples of Americans define
      health. Two questions were used to ascertain concepts of health: Are you healthy?
      and How do you know? (What does health mean to you?) These questions were added
      to omnibus telephone surveys conducted with two random samples of adults from the
      48 contiguous United States: one in 1995 (N = 1,000); the other in 2002 (N =
      1,011). The surveys also collected demographic data. This study focuses on cases
      with complete data (N = 950 in 1995, N = 967 in 2002). In both survey samples,
      more than 92% of respondents reported that they were healthy. Four distinct
      conceptions of health emerged from responses to the "how do you know" question:
      physical, psychosocial, capacity, and control. While prevalence varied with
      survey year as well as respondent age and education, these four concepts were
      evident in both 1995 and 2002. There are four robust concepts of health in
      America. Ongoing attention to these concepts may enhance efforts to communicate
      about and improve health.

PMID- 19180369
TI  - A 10-year systematic review of HIV/AIDS mass communication campaigns: Have we
      made progress?
AB  - The purpose of the current study was to conduct a 10-year systematic review of
      HIV/AIDS mass communication campaigns focused on sexual behavior, HIV testing, or
      both (1998-2007) and to compare the results with the last comprehensive review of
      such campaigns, conducted by Myhre and Flora (2000). A comprehensive search
      strategy yielded 38 HIV/AIDS campaign evaluation articles published in peer
      reviewed journals, representing 34 distinct campaign efforts conducted in 23
      countries. The articles were coded on a variety of campaign design and evaluation
      dimensions by two independent coders. Results indicated that compared with the
      previous systematic review (1986-1998 period), campaigns increasingly have
      employed the following strategies: (1) targeted defined audiences developed
      through audience segmentation procedures; (2) designed campaign themes around
      behavior change (rather than knowledge change); (3) used behavioral theories; (4)
      achieved high message exposure; (5) used stronger research designs for outcome
      evaluation; and (6) included measures of behavior (or behavioral intentions) in
      outcome assessments. In addition, an examination of 10 campaign efforts that used
      more rigorous quasi-experimental designs revealed that the majority (8 of 10)
      demonstrated effects on behavior change or behavioral intentions. Despite these
      positive developments, most HIV/AIDS campaigns continue to use weak (i.e.,
      preexperimental) outcome evaluation designs. Implications of these results for
      improved design, implementation, and evaluation of HIV/AIDS campaign efforts are
      discussed.

PMID- 19180370
TI  - Relationships among health literacy, knowledge about hormone therapy, self
      efficacy, and decision-making among postmenopausal health.
AB  - Little is known about how health literacy affects women's decisions about their
      menopausal health care. This exploratory study provides a crucial first step in
      gaining an understanding of the relationship between health literacy and
      potential factors such as knowledge, self-efficacy, and intent to take hormone
      therapy among postmenopausal women. Data were collected for 106 participants, age
      range 45-65, who were attending a family clinic. Participants completed a
      questionnaire that included questions on hormone therapy knowledge, self
      efficacy, behavioral intent concerning hormone therapy, and health literacy as
      well as demographic data. Inferential statistical tests were used to assess the
      relationships among health literacy, knowledge, self-efficacy, and behavioral
      intent concerning hormone therapy. Pearson correlations indicated a positive
      relationship between both health literacy and knowledge about hormone therapy (r
      = .64; p </= .01) and between health literacy and self-efficacy regarding hormone
      therapy (r = .69; p </= .01). Only two variables, health literacy and self
      efficacy, achieved sufficient strength to enter the stepwise regression. Sixty
      six percent of the variance for behavioral intent concerning hormone therapy was
      accounted for by decision self-efficacy, and 9% was accounted for by health
      literacy (R(2) = .75; p < .05). Further research to better understand the
      relationship between health literacy and self-efficacy and the impact of these
      factors on actual health outcomes and decision making is likely to have important
      communication implications for both patients and their providers.

PMID- 19180371
TI  - Healthy depictions? Depicting adoption and adoption news events on broadcast
      news.
AB  - Given that the public uses the media to learn about adoption as a family form,
      this study analyzes U.S. television news coverage of adoption between 2001 and
      2005 (N = 309 stories), to identify the types of news events covered about
      adoption. A majority of news stories covered fraud, crime, legal disputes, and
      negative international adoption cases. Adoptees as defective or unhealthy were
      depicted more in negative news event stories, birth parents appeared less
      overall, and adoptive parents were most likely to have healthy depictions in
      positively oriented adoption experience, big family, and reunion stories.
      Although three quarters of the stories used primary adoption participants as news
      sources, one-third of the negative event stories did not contain healthy
      depictions of adoption participants. The authors discuss ways journalists and
      researchers might improve adoption news coverage.

PMID- 19180372
TI  - Physician trust moderates the Internet use and physician visit relationship.
AB  - Prior research found that Internet use for health information leads to more
      frequent physician visits. This study explores the conditions under which this
      effect works by examining whether trust in health information from health
      professionals plays a moderating role in the associations between Internet use
      and the frequency of physician visits. This study uses a two-wave panel dataset
      with a U.S. nationally representative sample gathered in 2005 and 2006. The
      results show that the effects of Internet use on physician visits are larger for
      those who have low levels of trust in both cross-sectional and panel analyses.

PMID- 19180373
TI  - Physician adoption of personal digital assistants (PDA): testing its determinants
      within a structural equation model.
AB  - Research has begun to explore the determinants of personal digital assistant
      (PDA) adoption in health care. Much of this research has, however, been
      inconsistent in its treatment of key constructs and its methodological
      approaches. The current study takes a stricter approach and tracks the pre- and
      postadoption beliefs of physicians provided with an actual PDA within a single
      health care facility in the United States. Results show that age, position in
      hospital, beliefs about health IT, and cluster ownership are significant, direct
      predictors of the physician's preadoption beliefs about PDAs. Contrary to prior
      research findings, both ease of use and usefulness perceptions significantly
      influenced the physician's intent to adopt PDAs. More important, results show
      that physicians focus on a broader range of PDA factors during preadoption
      assessment of the technology, while actual use is based solely on the PDA's ease
      of use. Moreover, the preadoption usefulness perceptions do not influence
      postadoption usefulness. Hence, the cognitive and affective determinants of
      intent to use are seemingly different from those used to evaluate PDA use.

PMID- 19180375
TI  - Respirator physiological effects under simulated work conditions.
AB  - This study compared the physiological impacts of two respirator types in
      simulated work conditions. Fifty-six subjects included normal volunteers and
      persons with mild respiratory impairments (chronic rhinitis, mild COPD, and mild
      asthma). Respiratory parameters and electrocardiogram were measured using
      respiratory inductive plethysmography while performing eight work tasks involving
      low to moderate exertion using two respirators: (1) a dual cartridge half face
      mask (HFM) respirator, and (2) the N95. Mixed model regression analyses
      evaluating the effect of task and respirator type showed that task affected tidal
      volume, minute ventilation, breathing frequency and heart rate; all were greater
      in heavier tasks. Although respirator type did not affect respiratory volume
      parameters and flow rates, the HFM led to increase in the inspiratory time,
      reduction of the expiratory time, and increase in the duty cycle in comparison
      with the N95. The magnitude of differences was relatively small. The results
      suggest that most individuals, including persons with mild respiratory
      impairments, will physiologically tolerate either type of respirator at low to
      moderate exertion tasks. However, because effective protection depends on proper
      use, differences in subjective effect may have greater impact than physiological
      differences. Using respirators may be feasible on a widespread basis if necessary
      for maintaining essential services in the face of widespread concern about an
      infectious or terrorist threat.

PMID- 19180376
TI  - Welcome to the bioethics presidency.

PMID- 19180377
TI  - Response to open peer commentaries on "Must research participants understand
      randomization?".

PMID- 19180378
TI  - Must research participants understand randomization?
AB  - In standard medical care, physicians select treatments for patients based on
      clinical judgment, considering which treatment is best for the individual
      patient, given the patient's history and circumstances. In contrast,
      investigators conducting randomized clinical trials select treatments for
      participants based on a random selection process. Because this process represents
      a significant departure from the norms of standard medical care, it is widely
      assumed that potential research participants must understand randomization to
      give valid informed consent. This assumption, together with data that many
      research participants do not understand randomization, implies that randomized
      clinical trials often fail to obtain adequately informed consent. Before
      accepting this conclusion, and before initiating extensive efforts to improve
      research participants' understanding of randomization, we should assess the
      plausible, but rarely analyzed assumption that participants need to understand
      randomization to give valid informed consent for randomized clinical trials.

PMID- 19180379
TI  - Response to commentaries on "Patient autonomy for the management of chronic
      conditions: a two-component re-conceptualization".

PMID- 19180380
TI  - Response to open peer commentaries on "Three ways to politicize bioethics".

PMID- 19180381
TI  - The dirty little truth: we want them to understand, but not really...

PMID- 19180382
TI  - To study, perchance to treat.

PMID- 19180383
TI  - Equipoise trumps randomization.

PMID- 19180384
TI  - Understanding randomization: helpful strategies.

PMID- 19180385
TI  - Randomization and the transactional framework for informed consent.

PMID- 19180386
TI  - Randomization can be risky.

PMID- 19180387
TI  - If children understand drawing straws and flipping coins, research participants
      can understand randomization.

PMID- 19180388
TI  - Equipoise may be in the eye of the beholder.

PMID- 19180389
TI  - Patient autonomy for the management of chronic conditions: a two-component re
      conceptualization.
AB  - The clinical application of the concept of patient autonomy has centered on the
      ability to deliberate and make treatment decisions (decisional autonomy) to the
      virtual exclusion of the capacity to execute the treatment plan (executive
      autonomy). However, the one-component concept of autonomy is problematic in the
      context of multiple chronic conditions. Adherence to complex treatments commonly
      breaks down when patients have functional, educational, and cognitive barriers
      that impair their capacity to plan, sequence, and carry out tasks associated with
      chronic care. The purpose of this article is to call for a two-component re
      conceptualization of autonomy and to argue that the clinical assessment of
      capacity for patients with chronic conditions should be expanded to include both
      autonomous decision-making and autonomous execution of the agreed-upon treatment
      plan. We explain how the concept of autonomy should be expanded to include both
      decisional and executive autonomy, describe the biopsychosocial correlates of the
      two-component concept of autonomy, and recommend diagnostic and treatment
      strategies to support patients with deficits in executive autonomy.

PMID- 19180390
TI  - Decisional versus performative capacities: not exactly a new idea.

PMID- 19180391
TI  - Patient autonomy writ large.

PMID- 19180392
TI  - Expanding autonomy; contracting informed consent.

PMID- 19180393
TI  - Towards a comprehensive concept of patient autonomy.

PMID- 19180394
TI  - Executive autonomy, multiculturalism and traditional medical ethics.

PMID- 19180395
TI  - Autonomy and chronic illness: not two components but many.

PMID- 19180396
TI  - Three ways to politicize bioethics.
AB  - Many commentators today lament the politicization of bioethics, but some suggest
      distinguishing among different kinds of politicization. This essay pursues that
      idea with reference to three traditions of political thought: liberalism,
      communitarianism, and republicanism. After briefly discussing the concept of
      politicization itself, the essay examines how each of these political traditions
      manifests itself in recent bioethics scholarship, focusing on the implications of
      each tradition for the design of government bioethics councils. The liberal
      emphasis on the irreducible plurality of values and interests in modern
      societies, and the communitarian concern with the social dimensions of
      biotechnology, offer important insights for bioethics councils. The essay finds
      the most promise in the republican tradition, however, which emphasizes
      institutional mechanisms that allow bioethics councils to enrich but not dominate
      public deliberation, while ensuring that government decisions on bioethical
      issues are publicly accountable and contestable.

PMID- 19180397
TI  - Republicanism in bioethics?

PMID- 19180398
TI  - Small-r-republicans, big-R-Republicans, and government bioethics councils.

PMID- 19180399
TI  - Bioethics and politics: rules of engagement.

PMID- 19180400
TI  - Politics by another name.

PMID- 19180401
TI  - The political condition of bioethics.

PMID- 19180403
TI  - [The HIV vaccine is coming--but when?].

PMID- 19180404
TI  - [Health insurance discount contracts: problems and risks for the general
      practitioner in the medical care of patients with chronic illness].
AB  - BACKGROUND AND OBJECTIVE: The German federal Health Insurance law to strengthen
      competition between the pharmaceutical companies commits pharmacies to hand out
      drugs from discount contract drug suppliers of a patient's health insurance
      company. Thus patients are confronted with constantly changing drug packets. This
      study aimed at exploring whether patients have been properly informed about the
      new discount contracts and if they have experienced changes and problems in their
      long- term medications. METHODS: Between May and June 2008 male and female
      patients older than 50 years who had a statutory health insurance and had been
      diagnosed with coronary heart disease for at least one year answered a
      standardized questionnaire filled in by doctors' assistants or general
      practitioners in the doctors' network "Weschnitztal". RESULTS: Of the 188
      patients participated in this study 63,8% were informed about health insurance
      discount contracts. 31,3% of the patients reported that a positive effect due to
      the discount contracts was that they were discharged from paying the drug
      prescription fee, 22,2% mentioned that cost saving for the health insurance could
      also be positive. 120 patients (63,8%) knew that the names of their long-term
      drugs could change.101 of the questioned patients (53,7%) identified a change in
      their long-term drugs, 51,5% felt insecure about the permanent changes. 21,7%
      experienced adverse e effects due to the new drugs. 19% of the patients had
      serious problems regarding medication intake. CONCLUSION: This study demonstrates
      that the information which patients have on the new health insurance law is not
      adequate enough. Many of them felt insecure because of the changes of long-term
      medications. One fifth of the patients reported errors in their drug intake or
      their confusion about their drugs. There is a high risk that these circumstances
      may trigger further diseases or complications. The cost savings as intended by
      the health insurance companies may therefore not be achieved by discount
      contracts.

PMID- 19180405
TI  - [Parenteral combined quinine-artesunate therapy in life-threatening malaria].
AB  - HISTORY AND CLINICAL FINDINGS: A 31-year old French woman of congolese origin was
      referred to the intensive care unit of our University Hospital after a visit to
      the Democratic Republic of Congo in a highly febrile and semi-conscious status.
      INVESTIGATIONS: Microscopy of stained thin and thick blood films revealed
      Plasmodium falciparum trophzoites with a high parasitaemia of 50 % and confirmed
      the clinical suspicion of a life-threatening malaria. TREATMENT AND COURSE:
      Immediate intravenous quinine with a loading dose of 20 mg/kg body weight was
      initiated followed by 10 mg/kg every 8 hrs. Since the patient lost consciousness,
      artesunate was added six hours later in the recommended dose of 2.4 mg/kg
      immediately, repeated after 12 and 24 hrs, followed by a daily dose of 2.4 mg/kg.
      Furthermore, clindamycin at a dose of 20 mg/kg body weight / d i. v. was given.
      Anaemia was corrected by 4 erythrocyte concentrates until a haemoglobina
      concentration of 9.6 g/dl was reached. Now the patient rapidly recovered, and
      parasitaemia dropped to 0.1 % within 24 hrs. Already the following day blood
      films cleared completely from malaria parasites. CONCLUSION: The case illustrates
      the rapid efficacy of a combined parenteral quinine-artesunate therapy in life
      threatening falciparum malaria with an unusually high parasitaemia.

PMID- 19180406
TI  - [45-year-old female with recurrent upper abdominal pain and progressive dyspnoe].

PMID- 19180407
TI  - [Hypertension and pregnancy].

PMID- 19180408
TI  - [Hypertension in pregnancy].

PMID- 19180409
TI  - [Should the prevention of obesity be a task for medical practitioners?].

PMID- 19180410
TI  - [Fall Congress for Integrative Medicine--model for the future].

PMID- 19180411
TI  - [Rejection of medical evidence through bias].

PMID- 19180412
TI  - [Hypercalcemic crisis due to primary hyperparathyroidism].

PMID- 19180414
TI  - [German-language questionnaires for the standardized assessment of fecal
      incontinence and quality of life].
AB  - BACKGROUND AND OBJECTIVE: The severity of fecal incontinence is usually assessed
      in grades based on medical history. However, this grading does not consider stool
      frequency and thus the impairment suffered by the patients. A German translation
      of the incontinence scores of the Cleveland Clinic (CCS) for a standardized
      measurement disability has been recommended but not yet tested. Similarly, the
      impact of fecal incontinence on quality of life needs to be assessed with a
      specific assessment. The Fecal Incontinence Quality of Life Scale (FIQoL) is
      available for this, but not yet a German-language version. PATIENTS AND METHODS:
      For the German version of the CCS and the FIQoL we first evaluated linguistic
      aspects via translation and back-translation. We then compared the response to
      the translated questionnaires of a sample of 158 German patients who had fecal
      incontinence with those reported in English-language publications. RESULTS: The
      German versions were judged to be successful. The comparison with six published
      studies showed similar scores in the CCS and in all subscales of the FIQoL.
      CONCLUSION: Satisfactory German-language questionnaires are now available to
      assess the severity of fecal incontinence and specific aspects of the quality of
      life.

PMID- 19180415
TI  - [Diagnostic pitfall: basal cell carcinoma arising in a therapy-resistant chronic
      venous ulcer of the lower leg].
AB  - HISTORY: A 96-year-old woman attended our department with an ulcer on the lower
      leg. It looked typical of an ulcer due to chronic venous insufficiency an had
      been resistant to treatment for 20 years. INVESTIGATIONS: On the left lower leg
      there was a 5 x 5 cm ulcer with a sharply demarkated border. Because of its
      chronicity and its resistance to treatment several biopsies were taken from its
      borders. DIAGNOSIS, TREATMENT AND CLINICAL COURSE: Histopathologically
      examination revealed a basal cell carcinoma. The ulcer was excised with a wide
      margin and the wound closed with a mesh-graft. CONCLUSION: This case demonstrates
      the need of re-evaluating the pathology of chronic ulcers due to venous stasis in
      the leg to exclude malignancy.

PMID- 19180416
TI  - [Acute abdomen from the internal medicine point of view].
AB  - The interdisciplinary management of acute abdominal pain involves experienced
      specialists in both internal medicine and visceral surgery. The essential
      approach is to shorten the time between begin of symptoms, contact with a medical
      practitioner, diagnosis and therapy through identification of patients at risk,
      eg. of mesenteric ischemia. The characteristics of abdominal pain may help to
      identify the underlying disease. However, in children, in the elderly or in
      immune-compromised patients the symptoms may be nonspecific. Effective management
      of acute abdominal pain involves a careful history taking, ultrasound,
      electrocardiography and blood tests. Computed tomography of abdominal organs and
      visceral vessels is probably important already at the beginning of the diagnostic
      work up. Time consuming diagnostic steps should not be undertaken.

PMID- 19180417
TI  - [50-year-old man with weight loss and splenomegaly].

PMID- 19180418
TI  - [Prevention and therapy of reactivation of hepatitis B in immunosuppressed
      patients].
AB  - Immunosuppression because of local or systemic chemotherapy or immunosuppressive
      therapy of autoimmune diseases is an increasing risk for reactivation of
      hepatitis B and may lead to acute hepatitis and rarely to fulminant hepatitis.
      Intensive immunosuppression, e. g. in advance of bone marrow transplantation, may
      lead to re-seroconversion with loss of anti-HBs and detection of HBsAg and HBV
      DNA and a risk of (fulminant) hepatitis. Distinct chemotherapeutics and
      immunosuppressive medication promote reactivation or re-seroconversion of HBV
      infection. Several studies have shown a significant benefit by antiviral therapy
      with nucleosidanalogue lamivudine to avoid reactivation. For other nucleoside
      analogues (telbivudine, entecavir) or nucleotide analogues (adefovir dipivoxil,
      tenofovir) larger experiences are yet missing in this situation. Prophylaxis with
      antiviral agents may be superior to therapy of reactivation. Prior to onset of
      immunosuppressive treatment patients must be tested for HBV. Patients without
      detection of HBsAg and without sufficient anti-HBs-titer should receive active
      immunisation. In case of chronic HBV infection antiviral therapy should be
      initiated before intense immunosuppression. In case of HBV infection in medical
      history (anti-HBc positive, HBsAg negative) HBV serostatus should be tested
      frequently. In case of reactivation, therapy with nucleos(t)ide analogue should
      immediately be initiated. In case of bone marrow transplantation prophylaxis with
      nucleos(t)idanalogue has to be initiated before onset of treatment if anti-HBc is
      detectable, independent from HBsAg result.

PMID- 19180419
TI  - [Sphingolipids and their medical impact].
AB  - Sphingolipids are known to function as structural components in cell membranes,
      but they also have signalling properties. Sphingosine 1-phosphate (S1P), in
      particular, is an extracellular messenger that activates five G protein-coupled
      cell surface receptors, and regulates important physiological functions in the
      cardiovascular and immune system, in hearing, and fertility. Tight regulation of
      receptor-available S1P, establishment of concentration gradients and the close
      interplay between S1P and its receptors are necessary requirements in a multitude
      of processes. Pharmacological and genetic studies in animals have demonstrated
      that altered S1P concentrations in blood and organs, as well as mutated
      expression of S1P receptors in certain cell systems can be causative, but may
      also be efficacious medication in selected diseases. Sphingolipids and their
      receptors are, therefore, current targets for medical research.

PMID- 19180420
TI  - [Operation performed by another physician than the one the patient wished for in
      the pre-operation discussion. Verdict by the Provincial High Court and Court of
      Appeal in Koln on August 25, 2008].

PMID- 19180421
TI  - [Interpretation of oral glucose tolerance tests].

PMID- 19180425
TI  - Endoscopic resection of ectopic pancreas in the minor papilla.

PMID- 19180424
TI  - [Epidemiology of cutaneous vascular neoplasms and malformations in childhood].
AB  - PURPOSE: A representative compilation of data on the incidence and prevalence of
      benign cutaneous vascular neoplasms and malformations in childhood has been made.
      PATIENTS, MATERIALS AND METHODS: A review of the literature has been made and
      basic data from an own epidemiological survey in the province of Tyrol (Austria)
      in 6-year-old children are evaluated. RESULTS: For capillary malformations with
      spontaneous regression (salmon patches), the reported numbers usually vary
      between 20 and 30% of the newborns, while true, persisting capillary
      malformations (port-wine stains) can be found in about 1%. Strawberry angiomas
      are found in about 3% of mature newborns but in up to 12.5% of preterm children.
      Complex vascular malformations or severe cases of vascular tumours are very rare.
      CONCLUSION: All in all, vascular lesions are very common findings in childhood,
      but in most cases harmless and transient in nature. The number of lesions that
      may require adequate but usually uncomplicated treatment amounts to about one
      percent of children (strawberry angiomas and port-wine stains). Complex and/or
      life-threatening severe vascular tumours and malformations that represent a
      considerable therapeutic challenge are extremely rare events.

PMID- 19180426
TI  - Endoscopic ultrasonography of the small bowel.

PMID- 19180427
TI  - [Progestagen use in oral contraception - basic knowledge].
AB  - The effects of most prostagens used in hormone replacement therapy (HRT) and in
      hormonal contraception are not identical. They differ in their structure, the
      metabolisation, their bioavailability and their partial activities. Therefore, it
      does not make any sense to declare that the different progestagens with their
      different profiles belong to one class of substances, having all the same effect.
      In function of their partial activities, progestagens are used today specifically
      for HRT, for hormonal contraception or as an anti-androgen. Because of their
      metabolic profile, some newer progestagens can be considered to be specifically
      favourable, such as Norpregnanes, Dienogest and Drospirenone. This review
      summarizes the properties and partial activities of progestagens used today and
      analyzes its clinical consequences.

PMID- 19180428
TI  - [Effect of combined hormonal contraceptives on the vascular endothelium und new
      cardiovascular risk parameters].
AB  - Epidemiological studies indicate an increased cardiovascular risk in users of
      combined oral contraceptives (COC) but not progestagen-only preparations. A
      specially high risk was observed in women older than 35 years with additional
      cardiovascular risk factors like smoking or hypertension. The mechanisms
      underlying arterial occlusion can not be explained by hormonal effects on the
      vascular tonus, nor by effects on newer risk parameters like homocysteine or
      transforming growth factor-beta. However, CRP increases during oral and
      transdermal COC use, an effect which can not be observed during use of a
      progestagen-only implant. Studies concerning the effect of COC on the vasotonus,
      nitric oxide, homocysteine and CRP usually include young healthy women with
      intact endothelial function. Females with nicotinabusus, hypertension and
      hypercholesterolemia have a damaged endothelium. The effect of hormonal treatment
      on the endothelium in these women might include decreased ability to release the
      strong vasodilator nitric oxid and as a consequence of that impaired
      vasodilation.

PMID- 19180429
TI  - [Oral contraception - doses and way of administration].
AB  - Since the correlation between the amount of Ethinylestradiol (EE) and the
      thromboembolic risk has been recognized, the development of new oral
      contraceptives (OC) has been characterized by a constant lowering of the EE
      dosage. The consecutive decrease of ovulation inhibition has been compensated by
      the introduction of potent progestagens. Therefore, the contraceptive safety has
      been maintained in presence of less side-effects. The effect of ultra-low-dose OC
      on acne and seborrhea remains beneficial. The effect of ultra-low-dose OC on bone
      is contradictory. Because there are fundamental differences between Estradiol and
      EE, the thromboembolic risk is not decreased by the parenteral administration of
      EE. In users of the contraceptive patch, it is even increased. EE is not bound at
      SHBG. Because of its Ethinyl group, the inactivation of EE occurs slowly.
      Therefore, EE reaches the liver in a low but constant concentration where it
      modifies many estrogen-dependent hepatic parameters significantly. One of these
      is hemostasis. It is generally accepted that such changes are responsible for the
      increased thromboembolic risk of the contraceptive patch and vaginal ring. A
      reduction of the hormone-free interval of the pill to 5 or 4 days results in a
      complete suppression of the ovarian function, a reliable ovulation inhibition and
      an increase of the contraceptive efficacy in spite of a reduction of the EE
      dosage to 20 microg or 15 microg.

PMID- 19180430
TI  - [Long-cycle treatment in oral contraception].
AB  - Surveys show that most women desire a change in their menstrual pattern in the
      sense that they would prefer less menstruations or even amenorrhea. On this
      behalf, there is no difference between women having spontaneous natural cycles
      and women taking the pill. The main reasons are less menstrual bleedings, better
      hygienic conditions, a better quality of life and less blood loss. In women
      wanting regular monthly periods, the opinion is dominant that suppression of
      menstrual bleedings is "unnatural". It is therefore primordial to inform women
      that contraceptive safety is even increased in users following the long-cycle
      principal and that a fertility decrease has not to be feared. The benefit of the
      long-cycle OC is a reduction of the hormonal fluctuations induced by the pill
      free interval with its consecutive somatic and mental symptoms, as well as an
      increased contraceptive safety. The following cycle- and menstruation-dependent
      symptoms as listed as an indication for the long-cycle use: Endometriosis,
      hypermenorrhea, dysmenorrhea, hemorrhagic diathesis, uterine fibroma, polyzystic
      ovary syndrome, migraine due to estrogen-deficiency in the pill-free interval as
      well as premenstrual syndrome.

PMID- 19180431
TI  - [Contraception in adolescence and perimenopause].
AB  - The risk-benefit-ratio of hormonal contraception (OC) is positive in adolescents
      as well as in women over 40 years of age if some essential rules are respected.
      In adolescents, the acquirement of a normal peak bone mass has to be guaranteed
      by the use of the OC. The dosage of the OC has to be adapted individually to the
      basic hormonal situation. In women over 40, contraindications such as
      hypertension, obesity, smoking or dyslipidemia have to be actively excluded. In
      both groups of age, the risk of a correctly indicated OC is inferior to the risk
      of an unwanted pregnancy.

PMID- 19180432
TI  - [Contraception in women with special problems].
AB  - Thromboembolic, cardiovascular and cerebrovascular events are age-dependent. They
      are extremely rare in young women. In contrast to the progestogen-only pills,
      oral contraceptives (OC) increase the risk of venous thrombosis. However,
      decisive ist the genetic predisposition. In healthy non-smokers of less than 35
      years of age, the risk to suffer from a myocardial infarction or a
      cerebrovascular accident is not increased by OC. Risk factors play a major role
      in the etiology of cardiovascular diseases. A detailed personal and family
      history is therefore mandatory before OC are prescribed. Very rarely, blood
      pressure is increased by OC. Although the incidence of such an increase is very
      low, blood pressure has to be measured regularly in pill users. Inspite of a
      current opinion, weight increase is rare in OC users. It depends mainly on the
      individual predisposition. An increased water retention can be reduced by a
      combined OC containing a progestagen with an antimineralocorticoid activity.
      Changes in insulin and blood sugar induced by low-dose OC are minimal so that
      they have no clinical relevance. OC do not increase the incidence of diabetes.
      Adrenal and thyroid function are not influenced by OC, there is no increased
      incidence of prolactinomas. Asthma is no contraindication against OC. If there is
      a cycle-dependent aggravation of the disease, OC might be beneficial. OC have no
      side-effects on the eye or the ear. In women suffering from lupus erythematodes
      having no renal participation, no increased antiphospholipid-antibodies and
      showing a stable or inactive disease, low-dose OC might be used.

PMID- 19180433
TI  - [Does hormonal contraception increase the risk for tumors?].
AB  - A non-contraceptive benefit of oral hormonal contraceptives (OC) is a diminished
      risk for certain benign as well as malignant tumours, such as benign breast
      tumours, uterine fibroids and ovarian cysts. Endometriosis itself is not
      positively influenced by OC, but dysmenorrhea is decreased. Modern low-dose OC do
      not increase the risk of liver cell adenomata or carcinomata. OC do not influence
      melanoma. Modern data do not suggest an increased risk for breast carcinoma in OC
      users. Long-term use of OC leads to a decreased risk of endometrial and
      colorectal carcinomata. Cervical carcinoma is not influenced directly by OC, but
      probably indirectly through a change in sexual behaviour. There is no increase of
      vulvar or vaginal carcinoma, even after long-term use of OC.

PMID- 19180434
TI  - [Contraceptive compliance - why is contraceptive failure still so frequent?].
AB  - Contraceptive compliance is defined as the correct use (according to the method
      specific prescriptions given by a medical professional and/or in written form as
      patient information leaflet) of a contraceptive method. Non-compliance describes
      a mismatch between the real behaviour of a user and the correct or ideal
      behaviour. There are various indicators that in general contraceptive compliance
      is far from ideal. Many studies report a rate of unintended pregnancies of 50%,
      half of them terminating in abortion. The abortion rate remains high even in
      countries with availability of advanced contraceptive technology. Especially with
      hormonal contraception and barrier methods the gap between correct and real use
      is large. Discontinuation rates per year reach up to 50%. Reasons for Non
      Compliance are (a) Lack of motivation to prevent a pregnancy due to ambivalence
      regarding the wish for a child as well as sexual and relationship issues (b)
      Cognitive factors (False information, misconceptions, irrational fears) (c)
      Difficult or lacking access to contraceptive methods (d) Behavioral errors and
      mistakes (Forgetting, loosing etc.) and (e) Side effects of the methods used.
      Three strategies to improve compliance can be distinguished: (a) Improving
      counselling; (b) Developing contraceptive methods which demand a low level of
      compliant behaviour by the user; (c) Improving quality of life of users by
      minimizing the negative side effects and maximizing the non contraceptive health
      benefits.

PMID- 19180435
TI  - [Hypertensive crisis].

PMID- 19180436
TI  - [Presyncope--CME-ECG 24].

PMID- 19180437
TI  - [Comment from the lipidologic viewpoint].

PMID- 19180438
TI  - [Comment from the cardiologic viewpoint].

PMID- 19180439
TI  - [Comment from the family practice viewpoint].

PMID- 19180440
TI  - [Muscle enzyme activity and exercise].
AB  - Exercise is classically associated with muscular soreness, presenting one to two
      days later, delayed onset muscular soreness. Blood muscle enzymes and protein
      elevations are characteristic, and may cause renal failure. Creatin phosphokinase
      peak appears on the fourth day and depends on exercise type and individual
      parameters. This effect is attenuated with repeated bouts, by habituation.
      Metabolic complications are rare. The knowledge of this reaction, even with
      common exercises, allows to postpone investigations for a complex metabolic
      disorder, or to avoid stopping a medication for fear of a side effect, as with
      statins. Indeed, it is necessary to wait for seven days without any exercise
      before interpreting an elevated CK result.

PMID- 19180441
TI  - [Sinusitis].

PMID- 19180442
TI  - [Change of body composition in an 81 year old runner in a 100 km run].
AB  - An 81-year-old runner completed successfully a 100-km-run within 19 h 45 min one
      year after coronary artery bypass surgery in recently diagnosed atherosclerotic
      coronary heart disease. Prior and shortly after the run, percent body fat, lean
      body mass, skeletal muscle mass and percent body water were determined non
      invasively both by the bioelectrical impedance analysis (BIA) and the traditional
      anthropometrical method. In addition, blood and urine samples were collected in
      order to evaluate fluid homeostasis. Proton nuclear magnetic resonance ((1)H-NMR)
      spectroscopy of the urine was performed in order to detect changes in metabolites
      of carbohydrate, fat and protein metabolism. Body mass increased by 1.9 kg,
      calculated skeletal muscle mass increased by 0.1 kg, calculated fat mass from
      anthropometric method decreased by 0.2 kg and from BIA by 3.1 kg. Calculated body
      water from BIA increased by 1.2 l and plasma volume decreased by 19%.
      Haematocrit, nitrogen urea, urinary specific gravity decreased whilst sodium
      increased. (1)H-NMR spectroscopy revealed an increase of ketone bodies after the
      run. To demonstrate a decrease of skeletal muscle mass after a 100-km-run, we
      should wait with the measurements of body masses until body water has reached pre
      race value. The increase of body water is unclear. In future studies, additional
      methods should be performed to provide information whether skeletal muscle mass
      decreased after endurance performance and whether metabolites of skeletal muscle
      mass degradation may impair renal function.

PMID- 19180446
TI  - [CME-ultrasonography 26/Solution].

PMID- 19180450
TI  - Two new Daphniphyllum alkaloids from the stems and leaves of Daphniphyllum
      calycinum.
AB  - Two new Daphniphyllum alkaloids, 9,10-epoxycalycinine A (1) and
      homodaphniphyllate (2), together with eight known related alkaloids, were
      isolated from the stems and leaves of Daphniphyllum calycinum. The structures of
      the new compounds 1 and 2 were elucidated on the basis of in-depth spectroscopic
      data analysis, by chemical derivatization, and by comparison of their
      spectroscopic data with those of known compounds.

PMID- 19180451
TI  - A simple and 'green' synthesis of polymer-based silver colloids and their
      antibacterial properties.
AB  - Stable silver colloids were prepared using polyethylene glycol (PEG) as an
      environment friendly reduction agent and stabilizer, and with H2O as solvent. The
      Ag colloids were characterized by UV/VIS spectroscopy, transmission electron
      microscopy (TEM), and atom force microscopy (AFM). TEM and AFM of the sample
      showed uniform and monodispersive particle distribution in the colloids. The
      particle size is found to be less than 10 nm. The antibacterial activity of the
      Ag colloids was also studied. The results showed that the sample had high
      antibacterial activity toward Gram-positive and Gram-negative bacteria, and
      fungi.

PMID- 19180449
TI  - StoneHinge: hinge prediction by network analysis of individual protein
      structures.
AB  - Hinge motions are important for molecular recognition, and knowledge of their
      location can guide the sampling of protein conformations for docking. Predicting
      domains and intervening hinges is also important for identifying structurally
      self-determinate units and anticipating the influence of mutations on protein
      flexibility and stability. Here we present StoneHinge, a novel approach for
      predicting hinges between domains using input from two complementary analyses of
      noncovalent bond networks: StoneHingeP, which identifies domain-hinge-domain
      signatures in ProFlex constraint counting results, and StoneHingeD, which does
      the same for DomDecomp Gaussian network analyses. Predictions for the two methods
      are compared to hinges defined in the literature and by visual inspection of
      interpolated motions between conformations in a series of proteins. For
      StoneHingeP, all the predicted hinges agree with hinge sites reported in the
      literature or observed visually, although some predictions include extra
      residues. Furthermore, no hinges are predicted in six hinge-free proteins. On the
      other hand, StoneHingeD tends to overpredict the number of hinges, while
      accurately pinpointing hinge locations. By determining the consensus of their
      results, StoneHinge improves the specificity, predicting 11 of 13 hinges found
      both visually and in the literature for nine different open protein structures,
      and making no false-positive predictions. By comparison, a popular hinge
      detection method that requires knowledge of both the open and closed
      conformations finds 10 of the 13 known hinges, while predicting four additional,
      false hinges.

PMID- 19180453
TI  - Composition of the cloacal gland secretion of tuatara, Sphenodon punctatus.
AB  - The lipophilic content of the cloacal gland secretion of the tuatara (Sphenodon
      punctatus) was investigated. GC/EI-MS Analysis of CH2Cl2 extracts of the
      secretions revealed triacylglycerols as major glandular constituents. Twelve
      major medium-chain fatty acids were found to be conjugated to glycerol in
      different combinations, resulting in complex mixtures. These acids were
      identified by transesterification and subsequent derivatization of natural
      samples, and their structures were verified by synthesis. The natural glycerides
      contain predominantly three of the following acids: octanoic (A), (E)- and (Z)
      oct-4-enoic (B and C, resp.), (4E,6Z)-octa-4,6-dienoic (tuataric acid; D), (R)
      2,6-dimethylheptanoic (E), (R)-2,6-dimethylhept-5-enoic (F), (Z)-dec-4-enoic (G),
      (4Z,7Z)-deca-4,7-dienoic (H), (R)-3,7-dimethyloct-6-enoic (I), (R)-4,8
      dimethylnon-7-enoic (J), (2R,6S)-2,6,10-trimethylundec-9-enoic (K), and (2R,5E)
      2,6,10-trimethylundeca-5,9-dienoic acids (L). Several additional acids, occurring
      in trace amounts only, were tentatively identified by MS. The elucidation of the
      absolute configuration of the acids was performed by GC on chiral phases.
      Individual tuatara show specific mixtures of glycerides with up to 100
      components. The individual mixtures may permit individual recognition because the
      bouquets seem to be stable over years.

PMID- 19180454
TI  - Aib and iva in the biosphere: neither rare nor necessarily extraterrestrial.
AB  - Fourty-nine species and strains of filamentous fungi of the genera Acremonium,
      Bionectria, Clonostachys, Emericellopsis, Hypocrea/Trichoderma, Lecythophora,
      Monocillium, Nectriopsis, Niesslia, Tolypocladium, and Wardomyces, deposited with
      the culture collection of the Centraalbureau voor Schimmelcultures (CBS) in
      Utrecht, The Netherlands, were grown on nutrient agar plates. Organic extracts of
      mycelia were analyzed after acidic total hydrolysis and derivatization by GC/SIM
      MS on Chirasil-L-Val for the presence of Aib (=alpha-aminoisobutyric acid, 2
      methylalanine) and DL-Iva (=isovaline, 2-ethylalanine). In 37 of the
      hydrolysates, Aib was detected, and in several of them D-Iva or mixtures of D-
      and L-Iva. Non-proteinogenic Aib, in particular, is a highly specific marker for
      a distinctive group of fungal polypeptides named peptaibols or, comprehensively,
      peptaibiotics, i.e., peptides containing Aib and displaying (anti)biotic
      activities. The biotic synthesis of these amino acids by filamentous fungi
      contradicts the still widespread belief that alpha,alpha-dialkyl-alpha-amino
      acids do not or rarely occur in the biosphere and, if detected, are of
      extraterrestrial origin. The abundant production of peptaibiotics by cosmopolitan
      species of microfungi has also to be considered in the discussion on the
      occurrence of Aib and Iva in ancient and recent sediments. The detection of trace
      amounts of Aib in ice samples of Antarctica that are devoid of meteorites might
      also be related to the presence of Aib-producing microorganisms, being either
      indigenous psychrophiles, or being transported and localized by mechanisms
      related to bioaerosols and cryoconites. The presence of microfungi being capable
      of producing alpha,alpha-dialkyl alpha-amino acids in terrestrial samples, and
      possible contamination of extraterrestrial materials are pointed out to be of
      relevance for the reliable interpretation of cosmogeochemical data.

PMID- 19180455
TI  - Chemical constituents of plants from the genus Brucea.

PMID- 19180456
TI  - Synthesis, characterization, and DNA-binding studies of mononuclear copper(II)
      phenanthroline-tyrosine complex.
AB  - The mononuclear complex [Cu(II)(phen)(L-Tyr)(H(2)O)] was synthesized and
      structurally characterized by elemental analysis, magnetic susceptibility,
      UV/VIS, IR, and EPR spectroscopy, and ESI mass spectrometry. The electronic and
      EPR spectral data suggest a square-pyramidal geometry around Cu(II). Absorption
      spectra, thermal denaturation, and fluorescence-spectroscopic studies were
      conducted to assess the interaction of the Cu(II) complex with calf thymus DNA
      (CT DNA). The intrinsic binding constant for CT DNA/complex (K(b)=3750 M(-1)) and
      Stern-Volmer quenching constant (K=0.39) were determined.

PMID- 19180457
TI  - Two new solanapyrone analogues from the endophytic fungus Nigrospora sp. YB-141
      of Azadirachta indica.
AB  - Two new solanapyrone analogues, solanapyrones N and O (1 and 2, resp.), and three
      known compounds, solanapyrone C (3), nigrosporalactone (4), and phomalactone (5),
      were isolated from the fermentation culture of Nigrospora sp. YB-141, an
      endophytic fungus isolated from Azadirachta indica A. Juss. The structures of the
      new compounds were elucidated on the basis of spectroscopic analysis. The
      antifungal activities of 1-5 towards seven phytopathogenic fungi were tested.
      Most of the compounds exhibited no or only weak antifungal activities.

PMID- 19180458
TI  - Revision of the absolute configuration at C(23) of lanostanoids and isolation of
      secondary metabolites from formosan soft coral Nephthea erecta.
AB  - Three new oxygenated ergostanoids, 1-3, one known ergostanoid, 4, one new
      trinoreudesmadienone, 5, one new calamenene type sesquiterpene, 6, and one known
      aristolane-type sesquiterpene, (-)-aristolone (7), have been isolated from the
      AcOEt extract of the soft coral Nephthea erecta. The structures of these
      compounds were determined by extensive spectroscopic and X-ray crystallographic
      analysis, as well as Mosher's method. We revised the absolute configuration at
      C(23) in the side chain of some lanostanoids as a result of the Mosher's products
      of 1 (i.e., 1a and 1b). The cytotoxicities against selected cancer cells and the
      anti-inflammatory effects of these tested metabolites 1-7 were determined in
      vitro.

PMID- 19180459
TI  - Compositions of essential oils and trichomes of Teucrium chamaedrys L. subsp.
      trapezunticum Rech. fil. and subsp. syspirense (C. Koch) Rech. fil.
AB  - Teucrium chamaedrys L. is a member of the Lamiaceae family and is represented in
      the Flora of Turkey by six subspecies. The aerial organs of T. chamaedrys L.
      subsp. trapezunticum Rech. fil. and subsp. syspirense (C. Koch) Rech. fil. bears
      numerous eglandular and glandular trichomes. Eglandular trichomes are simple,
      long-multicellular with cuticular micropapillae, and glandular hairs are of
      peltate and capitate types. The peltate hairs consist of a basal cell, a short
      unicellular stalk, and multicellular secretory head, and the capitate ones
      possess 1-2 stalk cells and one glandular head cell. The aerial parts were
      subjected to microdistillation for the isolation of volatiles. The analysis was
      simultaneously performed by using gas chromatography (GC) and gas
      chromatography/mass spectrometry (GC/MS). The major components were characterized
      as beta-caryophyllene (18%), nonacosane (12%), germacrene D (11%), caryophyllene
      oxide (7%), and alpha-pinene (7%) for subsp. trapezunticum, and caryophyllene
      oxide (23%), alpha-pinene (11%), and caryophyllenol II (5%) for subsp.
      syspirense.

PMID- 19180461
TI  - Doctoral students in the limelight at the 2nd Erlanger International Immunology
      Symposium.

PMID- 19180462
TI  - Proliferation of weakly suppressive regulatory CD4+ T cells is associated with
      over-active CD4+ T-cell responses in HIV-positive patients with mycobacterial
      immune restoration disease.
AB  - The role of Treg in patients with late-stage HIV disease, who commence
      combination antiretroviral therapy (cART) and develop pathogen-specific
      immunopathology manifesting as immune restoration disease (IRD) remains unclear.
      We hypothesised that Treg could be defective in either numbers and/or function
      and therefore unable to ensure the physiological equilibrium of the immune system
      in patients with IRD. Phenotypic and functional CD4(+) T-cell subsets of eight
      late-stage HIV patients with nadir CD4 count <50 cells/microL, who developed
      mycobacterial IRD upon commencing cART were compared with six therapy naive
      HIV(+) patients (nadir CD4 count <50 cells/microL), who did not develop an IRD
      after cART. Mycobacterium-avium-specific CD4(+) T cells from IRD patients
      produced high levels of IFN-gamma and IL-2 compared with controls (p<0.001).
      Surprisingly, we found a significant expansion of CD127(lo)Foxp3(+)CD25(+) Treg
      in IRD patients and a higher ratio of Treg to effector/memory subsets (p<0.001).
      In vitro suppression assays demonstrated reduced functional capacity of
      suppressor cells and diminished IL-10 secretion in IRD patients. Plasma levels of
      IL-7 were increased in patients and, interestingly, exogenous IL-7 and other
      cytokines strongly inhibited Treg suppression. These data suggest that despite
      substantial Treg expansion in IRD, their ability to induce suppression, and
      thereby downregulate aberrant immune responses, is compromised.

PMID- 19180463
TI  - DC contact with HIV-1-infected cells leads to high levels of Env-mediated virion
      endocytosis coupled with enhanced HIV-1 Ag presentation.
AB  - In HIV-infected patients, DC are likely to interact with both cell-free HIV and
      HIV-infected cells. We were interested in investigating the mechanism of virus
      transmission occurring upon contact between HIV-1-infected cells and DC, as well
      as the consequences for HIV-1 Ag-presenting activity. By comparing mixed co
      cultures with trans-well cultures, we observed that cell-to-cell contact strongly
      increased HIV-1 Env-mediated virion endocytosis in target DC. This endocytosis
      was independent of HIV-1 tropism, de novo infection, HIV-1 Env-CD4-dependent
      fusion, and immature DC activation/maturation. We also found that augmentation of
      HIV-1 endocytosis was closely correlated with strong, Env-dependent HIV-1 Ag
      presentation by DC. Our results provide a better understanding of the mechanisms
      underlying the induction of the anti-HIV adaptive immune response.

PMID- 19180466
TI  - DC therapy induces long-term NK reactivity to tumors via host DC.
AB  - We vaccinated mice with DC loaded with or without invariant NKT-cell ligand alpha
      galactosylceramide and evaluated long-term resistance against tumor challenge.
      When mice had been given either DC or DC/galactosylceramide and were challenged
      with tumor cells even 6-12 months later, both NK and NKT cells were quickly
      activated to express CD69 and produce IFN-gamma. The NK cells could resist a
      challenge with several different tumors in vivo. The activated NK and NKT cells
      could be depleted with anti-NK1.1 treatment. In spite of this, the activated
      cells recovered, indicating that tumor-responsive NK and NKT cells were being
      generated continuously as a result of vaccination with DC and were not true
      memory cells. The NK and NKT antitumor response in DC-vaccinated mice depended on
      CD4(+) T cells, but neither CD8(+)T cells nor CD4(+)CD25(+) regulatory T cells.
      However, both vaccine DC and host DC were required for the development of long
      term, tumor reactive innate immunity. These results indicate that DC therapy in
      mice induces long-lasting innate NK- and NKT-cell activation through a pathway
      that requires host DC and CD4(+) T cells and that the continued generation of
      active NK cells resists the establishment of metastases in vivo.

PMID- 19180465
TI  - Involvement of the intrinsic and extrinsic cell-death pathways in the induction
      of apoptosis of mature lymphocytes by the Escherichia coli heat-labile
      enterotoxin.
AB  - Escherichia coli heat-labile enterotoxin (LT) exhibits a broad range of
      immunomodulatory activities, including the induction of lymphocyte-programmed
      cell death. In previous studies, we have demonstrated that in vivo LT promotes
      apoptosis of immature T and B cells through the stimulation of endogenous
      glucocorticoids. In the present study, we show that the extrinsic cell-death
      pathway as well as the apoptosis-inducing factor do not participate in the LT
      induced elimination of thymocytes. In contrast to developing lymphocytes, LT
      promotes the death of mature lymphocytes by both glucocorticoid- and Fas death
      receptor/Fas ligand-dependent mechanisms. However, the dependency of these
      mechanisms in the LT-induced cell-death activity seems to be different among
      CD4(+) and CD8(+) T cells. Altogether, our study shows that the same bacterial
      toxin can induce apoptosis of lymphoid cells through several mechanisms depending
      on the status of differentiation of these cells.

PMID- 19180464
TI  - A novel IL-17-dependent mechanism of cross protection: respiratory infection with
      mycoplasma protects against a secondary listeria infection.
AB  - Immune responses to pathogens occur within the context of current and previous
      infections. Cross protection refers to the phenomena where infection with a
      particular pathogen provides enhanced resistance to a subsequent unrelated
      pathogen in an antigen-independent manner. Proposed mechanisms of antigen
      independent cross protection have involved the secretion of IFN-gamma, which
      activates macrophages, thus providing enhanced innate immunity against the
      secondary viral or bacterial pathogen. Here we provide evidence that a primary
      infection with the chronic respiratory pathogen, Mycoplasma pulmonis, provides a
      novel form of cross protection against a secondary infection with Listeria
      monocytogenes that is not mediated by IFN-gamma, but instead relies upon IL-17
      and mobilization of neutrophils. Mice infected with M. pulmonis have enhanced
      clearance of L. monocytogenes from the spleen and liver, which is associated with
      increased numbers of Gr-1(+)CD11b(+) cells and higher levels of IL-17. This
      enhanced clearance of L. monocytogenes was absent in mice depleted of Gr-1(+)
      cells or in mice deficient in the IL-17 receptor. Additionally, both the IL-17
      receptor and neutrophils were essential for optimal clearance of M. pulmonis.
      Thus, a natural component of the immune response directed against M. pulmonis was
      able to enhance clearance of L. monocytogenes.

PMID- 19180467
TI  - Imprinted DC mediate the immune-educating effect of early-life microbial
      exposure.
AB  - It has been long proposed that exposure to environmental factors early in life
      may have an educating effect on the development of immune regulatory functions.
      However, experimental studies on this issue are limited and the related molecular
      and cellular basis remains unclear. Here we report that neonatal exposure to
      killed bacteria (Chlamydia muridarum, originally called Chlamydia trachomatis
      mouse pneumonitis (MoPn)) changed the pattern of the hosts' immune responses to a
      model allergen (OVA) in adulthood. This was associated with altered phenotype and
      function of DC. We found that DC from adult mice treated neonatally with UV
      killed MoPn exhibited distinct patterns of surface marker and TLR expression and
      cytokine production from control mice (DC from adult mice neonatally treated with
      vehicle, (Sham-DC)). More importantly, DC from adult mice treated neonatally with
      UV-killed MoPn induced significantly lower type-2 antigen-specific T-cell
      responses than Sham-DC shown in DC:T co-culture experiments in vitro and in
      adoptive transfer experiments in vivo. In addition, depletion of T cells in vivo
      largely abolished the phenotypic and functional alterations of DC caused by
      bacterial exposure, suggesting the involvement of T cell in this process. Our
      study demonstrates a central role of DC in linking the early-life exposure to
      microbial products and the balanced development of immune regulatory functions
      and the involvement of T cells in imprinting of the DC function.

PMID- 19180468
TI  - Epithelial expression of human papillomavirus type 16 E7 protein results in
      peripheral CD8 T-cell suppression mediated by CD4+CD25+ T cells.
AB  - The role of thymic versus peripheral epithelium in the regulation of the antigen
      specific CD8 T-cell repertoire is still largely unresolved. We generated TCR-beta
      chain transgenic mice in which an increased frequency of peripheral CD8 T cells
      recognizes an epitope from a viral oncoprotein (HPV16E7) in the context of H
      2D(b) MHC class I. When T cells from these mice developed through the thymus of
      mice expressing functional E7 protein from a keratin 14 promoter, no major
      perturbation to transgenic T-cell development in the thymus was observed in these
      double-transgenic mice. In contrast, peripheral CD8 T-cell responses in the
      single-transgenic, K14E7 mice, including those unrelated to E7 antigen, are
      reduced whereas CD4 T-cell responses and antibody production are unchanged in
      these mice. Peripheral non-responsiveness among CD8 T cells was mediated largely
      by CD4(+)CD25(+) T cells. This suggested that epithelium expressing HPV16E7
      protein induces Treg that specifically down-regulate CD8 T-cell responses in the
      periphery. This may have important consequences for the treatment of cervical pre
      cancers and provides a model for understanding differential suppression of T and
      B lymphocyte subsets by Treg.

PMID- 19180469
TI  - Expression of IL-15RA or an IL-15/IL-15RA fusion on CD8+ T cells modifies
      adoptively transferred T-cell function in cis.
AB  - IL-15 and IL-15 receptor alpha (IL-15RA) play a significant role in multiple
      aspects of T-cell biology. However, given the evidence that IL-15RA can present
      IL-15 in trans, the functional capacity of IL-15RA expressed on CD8(+) T cells to
      modify IL-15 functions in cis is currently unclear. In the current study, we
      explore the functional consequences of IL-15RA, expression on T cells using a
      novel method to transfect naive CD8(+) T cells. We observed that RNA
      nucleofection led to highly efficient, non-toxic, and rapid manipulation of
      protein expression levels in unstimulated CD8(+) T cells. We found that
      transfection of unstimulated CD8(+) T cells with IL-15RA RNA led to enhanced
      viability of CD8(+) T cells in response to IL-15. Transfection with IL-15RA
      enhanced IL-15-mediated phosphorylation of STAT5 and also promoted IL-15-mediated
      proliferation in vivo of adoptively transferred naive CD8(+) T cells. We
      demonstrated that IL-15RA can present IL-15 via cis-presentation on CD8(+) T
      cells. Finally, we showed that transfection with a chimeric construct linking IL
      15 to IL-15RA cell autonomously enhances the viability and proliferation of
      primary CD8(+) T cells and cytotoxic potential of antigen-specific CD8(+) T
      cells. The clinical implications of the current study are discussed.

PMID- 19180470
TI  - PI3K limits TNF-alpha production in CD16-activated monocytes.
AB  - IgG complexes bind to Fc receptor family members FcgammaRI (CD64), FcgammaRII
      (CD32) and FcgammaRIII (CD16), activating cell MAPK and PI3K resulting in
      increased cytokine production from particular leukocytes. The signaling molecules
      involved in cytokine production after cross-linking CD16 have not been determined
      in monocytes. To address this question, TNF-alpha, IL-1beta and IL-6 were
      measured in activated monocytes after inhibiting MEK1/2, PI3K and glycogen
      synthase kinase-beta (GSK-3beta). The roles of GSK-3beta and NF-kappaB were then
      determined using reporter assays and siRNA treatment. The data suggested that an
      MAPK pathway stimulated TNF-alpha release but that active PI3K limited TNF-alpha,
      IL-1beta and IL-6 cytokine production after cross-linking CD16. PI3K was also
      shown to limit nuclear translocation of NF-kappaB. The limiting effect of PI3K on
      TNF-alpha production from activated monocytes depended on the decrease of GSK
      3beta activity, which significantly reduced the transactivation of NF-kappaB.
      Moreover, the TNF-alpha production induced by CD16 cross-linking was reduced in
      monocytes after treatment with siRNA against NF-kappaB, implying that this
      transcription factor functioned in TNF-alpha production. The results suggest that
      CD16 cross-linking activated PI3K and that active PI3K limited TNF-alpha
      production by inhibiting GSK-3beta activity, that blocked the action of NF
      kappaB.

PMID- 19180472
TI  - The immature B-cell subpopulation with low RAG1 expression is increased in the
      autoimmune New Zealand Black mouse.
AB  - Receptor editing is believed to play a critical role in immunological tolerance
      by altering the specificity of autoreactive B cells that emerge in the bone
      marrow. To study whether receptor editing is altered in autoimmune disease,
      recombination activation gene 1 (rag1) transcription in B cells from New Zealand
      Black (NZB) mice was examined by introducing a GFP gene at the rag1 locus. Female
      NZB(RAG1-GFP) mice generated autoantibodies and glomerular immune complexes.
      NZB(RAG1-GFP) mice did not display increased RAG1-GFP signal in B-1 and B-2 cells
      from the spleen and peritoneal cavity even following in vitro stimulation
      compared with C57BL/6(RAG1-GFP) control mice. The early B cells in the bone
      marrow were classified into RAG1-GFP(-) and RAG1-GFP(+) subpopulations. The RAG1
      GFP(-) immature B-cell population was in the minority in C57BL/6(RAG1-GFP) mice
      but was markedly increased in NZB(RAG1-GFP) mice. RAG1-GFP(-) immature B cells
      from NZB(RAG1-GFP) mice differentiated into anti-dsDNA Ab-producing cells after
      stimulation by LPS in vitro. RAG1-GFP(-) immature B cells from NZB(RAG1-GFP) mice
      displayed a different expression profile of transcription factors required for
      receptor editing, including pax5 and irf4, in comparison with the RAG1-GFP(+)
      immature B-cell population. In conclusion, the early B-cell subpopulation, which
      exhibits low RAG1 expression and presumably concomitantly low receptor editing,
      was found to be increased in NZB mice.

PMID- 19180471
TI  - Molecular basis of CD4 repression by the Swi/Snf-like BAF chromatin remodeling
      complex.
AB  - The Brg1/Brm-associated factor (BAF) chromatin remodeling complex directly binds
      the CD4 silencer and is essential for CD4 repression during T-cell development,
      because deletion of the ATPase subunit Brg1 or a dominant negative mutant of
      BAF57 each impairs CD4 repression in early thymocytes. Paradoxically, BAF57 is
      dispensable for remodeling nucleosomes in vitro or for binding of the BAF complex
      to the CD4 silencer in vivo. Thus, it is unclear whether BAF57-dependent CD4
      repression involves chromatin remodeling and, if so, how the remodeling
      translates into CD4 repression. Here we show that nucleosomes at the CD4 silencer
      occupy multiple translational frames. BAF57 dominant negative mutant does not
      alter these frames, but reduces the accessibility of the entire silencer without
      affecting the flanking regions, concomitant with localized accumulation of linker
      histone H1 and eviction of Runx1, a key repressor of CD4 transcription that
      directly binds the CD4 silencer. Our data indicate that precise nucleosome
      positioning is not critical for the CD4 silencer function and that BAF57
      participates in remodeling H1-containing chromatin at the CD4 silencer, which
      enables Runx1 to access the silencer and repress CD4. In addition to BAF57,
      multiple other subunits in the BAF complex are also dispensable for chromatin
      remodelling in vitro. Our data suggest that these subunits could also help
      remodel chromatin at a step after the recruitment of the BAF complex to target
      genes.

PMID- 19180473
TI  - Functional islet-specific Treg can be generated from CD4+CD25- T cells of healthy
      and type 1 diabetic subjects.
AB  - CD4(+)CD25(+)FOXP3(+) Treg cells require TCR engagement for suppressive function,
      thus ensuring that suppression occurs only in the presence of specific antigens;
      however, to date no studies have addressed the function of self-antigen-specific
      Treg in humans. These studies were designed to determine whether peripheral
      generation and function of islet antigen-specific adaptive Treg are defective in
      human subjects with type 1 diabetes (T1D). Islet antigen-specific adaptive Treg
      were induced in vitro by activation of CD4(+)FOXP3(-) T cells with glutamic acid
      decarboxylase and islet-specific glucose-6-phosphate catalytic subunit-related
      protein peptides in the context of T1D-associated HLA-DRbeta alleles. Antigen
      specific Treg were characterized using flow cytometry for FOXP3 and class II
      tetramer and assessed for the ability to inhibit proliferation. These adaptive
      Treg were then compared with influenza-specific Treg from the same study
      population. The function of tetramer(+) cells that expressed FOXP3 was similar
      for both influenza and islet antigens generated from control and T1D subjects. In
      fact, the potency of suppression correlated with FOXP3 expression, not antigen
      specificity. Thus, these data suggest that development of functional adaptive
      Treg can occur in response to islet antigens and activation of islet-specific
      Treg may potentially be used as a targeted immunotherapy in T1D.

PMID- 19180474
TI  - alpha-melanocyte-stimulating hormone suppresses bleomycin-induced collagen
      synthesis and reduces tissue fibrosis in a mouse model of scleroderma:
      melanocortin peptides as a novel treatment strategy for scleroderma?
AB  - OBJECTIVE: Recently, we found that human dermal fibroblasts (HDFs) express
      melanocortin 1 receptors (MC-1R) that bind alpha-melanocyte-stimulating hormone
      (alpha-MSH). In search of novel therapies for scleroderma (systemic sclerosis
      [SSc]), we used the bleomycin (BLM) model to investigate the effects of alpha-MSH
      on collagen synthesis and fibrosis. METHODS: Collagen expression in HDFs was
      determined by real-time reverse transcription-polymerase chain reaction (RT-PCR)
      and Western blot analyses. Signal transduction studies included pharmacologic
      blockade, immunofluorescence analysis, Western blotting, and reporter-promoter
      assays. Oxidative stress was measured by fluorescence-activated cell sorter
      analysis, and anti-oxidative enzyme levels were determined by real-time RT-PCR
      and Western blot analyses. The effect of alpha-MSH in the BLM mouse model of
      scleroderma was assessed by histologic, immunohistochemical, real-time RT-PCR,
      and protein analyses. Expression of MC-1R and pro-opiomelanocortin (POMC) in skin
      and HDF samples from patients with SSc was determined by RT-PCR and compared with
      that in samples from normal controls. RESULTS: Treatment with alpha-MSH (and
      related peptides) suppressed BLM-induced expression of type I and type III
      collagen in HDFs, and this effect was cAMP-dependent. Neither BLM nor alpha-MSH
      altered Smad signaling, but antioxidants inhibited BLM-induced collagen
      expression in vitro. In addition, alpha-MSH suppressed BLM-induced oxidative
      stress and enhanced the expression of superoxide dismutase 2 (SOD2) and heme
      oxygenase 1 (HO-1). In the BLM mouse model, alpha-MSH reduced skin fibrosis and
      collagen content and increased tissue levels of SOD2 and HO-1. In skin and HDFs
      from patients with SSc, both MC-1R and POMC messenger RNAs were detected, but
      there were no differences compared with healthy controls. CONCLUSION: Alpha
      melanocyte-stimulating hormone and related peptides that exert their effects via
      MC-1R may provide a novel antifibrogenic therapeutic tool for the treatment of
      fibrotic diseases such as scleroderma.

PMID- 19180475
TI  - Therapeutic effect of exosomes from indoleamine 2,3-dioxygenase-positive
      dendritic cells in collagen-induced arthritis and delayed-type hypersensitivity
      disease models.
AB  - OBJECTIVE: We have demonstrated previously that dendritic cells (DCs) modified
      with immunosuppressive cytokines, and exosomes derived from DCs can suppress the
      onset of murine collagen-induced arthritis (CIA) and reduce the severity of
      established arthritis. Indoleamine 2,3-dioxygenase (IDO) is a tryptophan
      degrading enzyme that is important for immune regulation and tolerance
      maintenance. DCs expressing functional IDO can inhibit T cells by depleting them
      of essential tryptophan and/or by producing toxic metabolites, as well as by
      generating Treg cells. This study was undertaken to examine the immunosuppressive
      effects of bone marrow (BM)-derived DCs genetically modified to express IDO, and
      of exosomes derived from IDO-positive DCs. METHODS: BM-derived DCs were
      adenovirally transduced with IDO or CTLA-4Ig (an inducer of IDO), and the
      resulting DCs and exosomes were tested for their immunosuppressive ability in the
      CIA and delayed-type hypersensitivity (DTH) murine models. RESULTS: Both DCs and
      exosomes derived from DCs overexpressing IDO had an antiinflammatory effect in
      CIA and DTH murine models. The suppressive effects were partially dependent on B7
      costimulatory molecules. In addition, gene transfer of CTLA-4Ig to DCs resulted
      in induction of IDO in the DCs and in exosomes able to reduce inflammation in an
      IDO-dependent manner. CONCLUSION: These results demonstrate that both IDO
      expressing DCs and DC-derived exosomes are immunosuppressive and
      antiinflammatory, and are able to reverse established arthritis. Therefore,
      exosomes from IDO-positive DCs may represent a novel therapy for rheumatoid
      arthritis.

PMID- 19180476
TI  - Study of functional variants of the BANK1 gene in rheumatoid arthritis.
AB  - OBJECTIVE: To investigate 1 functional (rs17266594) and 2 potentially functional
      (rs10516487 and rs3733197) BANK1 variants, which were previously identified as
      systemic lupus erythematosus (SLE) susceptibility markers, to test whether they
      are associated with rheumatoid arthritis (RA). METHODS: Four different cohorts
      were included in the study: 1,080 RA patients and 1,368 healthy controls from
      Spain, 278 RA patients and 568 healthy controls from Sweden, 288 RA patients and
      287 healthy controls from Argentina, and 288 RA patients and 288 healthy controls
      from Mexico. Samples were genotyped for BANK1 single-nucleotide polymorphisms
      (SNPs) using a TaqMan 5'-allele discrimination assay. Statistical analysis
      comparing allele and genotype distributions was performed with the chi-square
      test. RESULTS: We did not find a significant association between RA and the
      rs10516487 and rs17266594 BANK1 polymorphisms. However, there was an increase in
      the major alleles among RA patients. Similarly, for rs3733197, there was an
      increase in the major allele among patients in every cohort. Nevertheless, this
      skewing reached statistical significance in the Spanish (P = 0.01, odds ratio
      [OR] 1.17 [95% confidence interval (95% CI) 1.03-1.32]) and Argentinean (P =
      0.04, OR 1.31 [95% CI 1.00-1.72]) populations. We found a significant association
      of rs10516487 (P = 0.005, OR 1.15 [95% CI 1.04-1.28]) and rs3733197 (P = 0.0009,
      OR 1.17 [95% CI 1.07-1.29]) with RA in the pooled analysis. In a 3-SNP haplotype
      analysis, we found that the major TGG haplotype was significantly associated with
      RA (P = 0.005, OR 1.14 [95% CI 1.04-1.25]). In addition, we found a common CAA
      haplotype that was protective against RA (P = 0.0004, OR 0.82 [95% CI 0.74
      0.92]). CONCLUSION: These results suggest that BANK1 SNPs and haplotypes may
      contribute to RA susceptibility with a low risk.

PMID- 19180478
TI  - Replication of the association between the C8orf13-BLK region and systemic lupus
      erythematosus in a Japanese population.
AB  - OBJECTIVE: Recent genome-wide association studies identified an association
      between single-nucleotide polymorphisms (SNPs) in the C8orf13 region of BLK, the
      B lymphoid tyrosine kinase gene, with systemic lupus erythematosus (SLE) in
      Caucasians. The purpose of this study was to evaluate the significance of this
      region in the genetic background of Japanese patients with SLE. METHODS: Fourteen
      tag SNPs in the C8orf13-BLK region were genotyped in 327 Japanese patients with
      SLE and 322 healthy Japanese controls. The population-attributable risk
      percentage (PAR%) of rs13277113 in Japanese was compared with that in Caucasians
      as well as with that of other SLE susceptibility genes in Japanese. RESULTS: As
      in Caucasians, rs13277113A demonstrated the strongest association in Japanese (P
      = 1.73 x 10(-6) for the genotype frequency, P = 4.75 x 10(-7) for the allele
      frequency, odds ratio [OR] 2.44 [95% confidence interval (95% CI) 1.43-4.16]).
      The association in Japanese was consistent with a recessive model (P = 2.74 x 10(
      7), OR 2.27 [95% CI 1.66-3.11]). In contrast to the Caucasian population, this
      risk allele was the major allele in the Japanese population. Because both the
      risk allele frequency and the OR were higher in Japanese than in Caucasians, the
      PAR% of rs13277113 was estimated to be much higher in Japanese (35.4%) than in
      Caucasians (16.2%), and the second highest among the 6 confirmed SLE
      susceptibility genes in Japanese. CONCLUSION: The association of the C8orf13-BLK
      region with SLE was replicated in a Japanese population. Contribution of this
      region to the genetic predisposition to SLE appeared to be greater in Japanese
      than in Caucasians.

PMID- 19180477
TI  - Genetic risk factors for rheumatoid arthritis differ in Caucasian and Korean
      populations.
AB  - OBJECTIVE: Recent studies have identified a number of novel rheumatoid arthritis
      (RA) susceptibility loci in Caucasian populations. The aim of this study was to
      determine whether the genetic variants at 4q27, 6q23, CCL21, TRAF1/C5, and CD40
      identified in Caucasians are also associated with RA in a Korean case-control
      collection. We also comprehensively evaluated the genetic variation within
      PTPN22, a well-established autoimmune disease-associated gene. METHODS: We
      designed an experiment to thoroughly evaluate the PTPN22 linkage disequilibrium
      region, using tag single-nucleotide polymorphisms (SNPs) and disease-associated
      SNPs at 5 RA-associated loci recently identified in Caucasians, in 1,128 Korean
      patients with RA and 1,022 ethnically matched control subjects. We also
      resequenced the PTPN22 gene to seek novel coding variants that might be
      contributing to disease in this population. RESULTS: None of the susceptibility
      loci identified in Caucasian patients with RA contributed significantly to
      disease in Koreans. Although tag SNPs covering the PTPN22 linkage disequilibrium
      block were polymorphic, they did not reveal any disease association, and
      resequencing did not identify any new common coding region variants in this
      population. The 6q23 and 4q27 SNPs assayed were nonpolymorphic in this
      population, and the TRAF1/C5, CD40, and CCL21 SNPs did not show any evidence for
      association with RA in this population of Korean patients. CONCLUSION: The
      genetic risk factors for RA are different in Caucasian and Korean patients.
      Although patients of different ethnic groups share the HLA region as a major
      genetic risk locus, most other genes shown to be significantly associated with
      disease in Caucasians appear not to play a role in Korean patients with RA.

PMID- 19180479
TI  - Involvement of the Wnt signaling pathway in experimental and human
      osteoarthritis: prominent role of Wnt-induced signaling protein 1.
AB  - OBJECTIVE: Wnt signaling pathway proteins are involved in embryonic development
      of cartilage and bone, and, interestingly, developmental processes appear to be
      recapitulated in osteoarthritic (OA) cartilage. The present study was undertaken
      to characterize the expression pattern of Wnt and Fz genes during experimental OA
      and to determine the function of selected genes in experimental and human OA.
      METHODS: Longitudinal expression analysis was performed in 2 models of OA. Levels
      of messenger RNA for genes from the Wnt/beta-catenin pathway were determined in
      synovium and cartilage, and the results were validated using
      immunohistochemistry. Effects of selected genes were assessed in vitro using
      recombinant protein, and in vivo by adenoviral overexpression. RESULTS: Wnt
      induced signaling protein 1 (WISP-1) expression was strongly increased in the
      synovium and cartilage of mice with experimental OA. Wnt-16 and Wnt-2B were also
      markedly up-regulated during the course of disease. Interestingly, increased WISP
      1 expression was also found in human OA cartilage and synovium. Stimulation of
      macrophages and chondrocytes with recombinant WISP-1 resulted in interleukin-1
      independent induction of several matrix metalloproteinases (MMPs) and
      aggrecanase. Adenoviral overexpression of WISP-1 in murine knee joints induced
      MMP and aggrecanase expression and resulted in cartilage damage. CONCLUSION: This
      study included a comprehensive characterization of Wnt and Frizzled gene
      expression in experimental and human OA articular joint tissue. The data
      demonstrate, for the first time, that WISP-1 expression is a feature of
      experimental and human OA and that WISP-1 regulates chondrocyte and macrophage
      MMP and aggrecanase expression and is capable of inducing articular cartilage
      damage in models of OA.

PMID- 19180480
TI  - Altered integrin mechanotransduction in human nucleus pulposus cells derived from
      degenerated discs.
AB  - OBJECTIVE: Several studies have demonstrated biologic responses of intervertebral
      disc (IVD) cells to loading, although the mechanotransduction pathways have not
      been elucidated. In articular chondrocytes, which have a phenotype similar to
      that of IVD cells, a number of mechanoreceptors have been identified, with
      alpha5beta1 integrin acting as a predominant mechanoreceptor. The purpose of this
      study was to investigate the role of integrin signaling in IVD cells during
      mechanical stimulation and to determine whether RGD integrins are involved.
      METHODS: Human nucleus pulposus (NP) cells derived from nondegenerated and
      degenerated discs were subjected to dynamic compressive loading in the presence
      of an RGD inhibitory peptide. Expression of the alpha5beta1 heterodimer in IVD
      tissue was examined by immunohistochemistry and possible alternative
      mechanoreceptors by real-time quantitative polymerase chain reaction. RESULTS:
      Aggrecan gene expression was decreased following loading of NP cells from
      nondegenerated and degenerated discs. This response was inhibited by treatment
      with an RGD peptide in cells from nondegenerated, but not degenerated, IVDs.
      Immunohistochemistry demonstrated that expression of the alpha5beta1 heterodimer
      was unaltered in degenerated IVD tissue as compared with normal IVD tissue.
      CONCLUSION: Our results indicate that the mechanotransduction pathways are
      altered in cells from degenerated IVDs. Mechanosensing in NP cells from
      nondegenerated discs occurs via RGD integrins, possibly via the alpha5beta1
      integrin, while cells from degenerated discs show a different signaling pathway
      that does not appear to involve RGD integrins.

PMID- 19180481
TI  - B cell depletion with rituximab in patients with diffuse cutaneous systemic
      sclerosis.
AB  - OBJECTIVE: To determine the safety of rituximab, to provide preliminary data
      regarding the potential efficacy of rituximab, and to investigate the effects of
      rituximab on autoimmunity and fibrosis in patients with diffuse cutaneous
      systemic sclerosis (dcSSc). METHODS: Fifteen patients with dcSSc, all of whom
      experienced their first non-Raynaud's disease-associated disease manifestation
      within 18 months of trial entry, were recruited to receive 2 intravenous doses of
      rituximab (1,000 mg), administered 2 weeks apart. Safety, clinical, and
      exploratory outcomes were evaluated at baseline and at 6 months. The primary
      outcome was the change in the modified Rodnan skin thickness score (MRSS) at 6
      months compared with baseline. RESULTS: Adverse events included frequent infusion
      reactions and rare infections (urinary tract infection and dental abscess
      occurred in 1 patient each). The mean change in the MRSS between baseline and 6
      months was not significant. Results of pulmonary function tests and other
      measures of major organ involvement were stable. The modest B cell infiltrates
      that were present in most skin biopsy specimens at baseline were completely
      depleted at 6 months in most patients. Autoantibody titers showed only modest and
      variable changes after treatment. CONCLUSION: In this pilot study, treatment with
      rituximab appeared to be safe and well tolerated among patients with dcSSc.
      Rituximab treatment resulted in both depletion of circulating B cells and
      depletion of dermal B cells but had little effect on the levels of SSc-associated
      autoantibodies. Rituximab treatment did not appear to result in a significant
      beneficial effect on skin disease. The potential efficacy of rituximab in other
      organs such as the lung could not be clearly evaluated in this small open-label
      trial.

PMID- 19180482
TI  - Involvement of the Notch pathway in the regulation of matrix metalloproteinase 13
      and the dedifferentiation of articular chondrocytes in murine cartilage.
AB  - OBJECTIVE: To demonstrate the activation of the Notch signaling pathway during
      changes in the phenotype of chondrocytes in vitro, and to assess the influence of
      Notch on the production of chondrocyte markers. METHODS: Serial monolayer primary
      cultures of murine articular chondrocytes (MACs), as a model of chondrocyte
      dedifferentiation, were prepared. MACs were cultured with or without a Notch
      inhibitor and transfected with different Notch-expressing vectors. The Notch
      pathway and chondrocyte marker profiles were assessed by quantitative reverse
      transcription-polymerase chain reaction, immunoblotting, and immunocytochemistry.
      RESULTS: Successive passages of MACs resulted in a loss of type II collagen and
      aggrecan (chondrocyte differentiation markers), an increase in type I collagen
      (dedifferentiation marker), an increase in Notch ligands, and augmented target
      gene activity. The Notch inhibitor decreased the type II collagen protein content
      but had no effect on Col2a1 messenger RNA, while transfection with the
      constitutive active forms of the Notch1 receptor led to a decrease in type II
      collagen in transfected cells. In assays to investigate the mechanism of type II
      collagen breakdown, matrix metalloproteinase 13 (MMP-13) synthesis was regulated
      in a Notch-dependent manner, whereas MMP-2 synthesis was unchanged. CONCLUSION:
      The Notch signaling pathway is associated with decreased type II collagen
      production during the dedifferentiation of MACs in vitro. This may be correlated
      with the increase in MMP-13 production linked to activation of Notch.

PMID- 19180483
TI  - Employing molecular genetics of chondrodysplasias to inform the study of
      osteoarthritis.

PMID- 19180484
TI  - Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: the
      study on osteoarthritis progression prevention, a two-year, randomized, double
      blind, placebo-controlled trial.
AB  - OBJECTIVE: To assess the long-term effects of chondroitins 4 and 6 sulfate (CS)
      on the radiographic progression of, and symptom changes associated with, knee
      osteoarthritis (OA). METHODS: We performed an international, randomized, double
      blind, placebo-controlled trial in which 622 patients with knee OA were randomly
      assigned to receive either 800 mg CS (n = 309 patients) or placebo (n = 313
      patients) once daily for 2 years. Radiographs of the target knee, using the Lyon
      schuss view, were obtained at the time of enrollment and at 12, 18, and 24
      months. The minimum joint space width (JSW) of the medial compartment of the
      tibiofemoral joint was assessed by digital image analysis. The primary outcome
      was the loss in minimum JSW over 2 years. RESULTS: The intent-to-treat analysis
      demonstrated a significant reduction (P < 0.0001) in minimum JSW loss in the CS
      group (mean +/- SEM -0.07 +/- 0.03 mm) as compared with the placebo group (-0.31
      +/- 0.04 mm). The percentage of patients with radiographic progression > or =0.25
      mm was significantly reduced in the CS group compared with the placebo group (28%
      versus 41% [P < 0.0005]; relative risk reduction 33% [95% confidence interval 16
      46%]). The number of patients needed to treat was 8 (95% confidence interval 5
      17). Pain improved significantly faster in the CS group than in the placebo group
      (P < 0.01). There were no differences in safety between groups. CONCLUSION: The
      long-term combined structure-modifying and symptom-modifying effects of CS
      suggest that it could be a disease-modifying agent in patients with knee OA.

PMID- 19180486
TI  - Increased expression of CD40 on bone marrow CD34+ hematopoietic progenitor cells
      in patients with systemic lupus erythematosus: contribution to Fas-mediated
      apoptosis.
AB  - OBJECTIVE: Patients with systemic lupus erythematosus (SLE) display increased
      apoptosis of bone marrow (BM) CD34+ hematopoietic progenitor cells. This study
      was undertaken to evaluate the expression of CD40 and CD40L in the BM of SLE
      patients, and to explore the possible involvement of these molecules in apoptosis
      of CD34+ cells. METHODS: The proportion and survival characteristics of CD40+
      cells within the BM CD34+ fraction from SLE patients and healthy controls were
      evaluated by flow cytometry. The production of CD40L by BM stromal cells was
      assessed using long-term BM cultures, and the effect of CD40L on the survival
      characteristics and clonogenic potential of CD34+ cells was evaluated ex vivo by
      flow cytometry and clonogenic assays. RESULTS: SLE patients displayed an
      increased proportion of CD40+ cells within the CD34+ fraction as compared with
      controls. The CD34+CD40+ subpopulation contained an increased proportion of
      apoptotic cells compared with the CD34+CD40- fraction in patients and controls,
      suggesting that CD40 is involved in the apoptosis of CD34+ cells. Stimulation of
      patients' CD34+ cells with CD40L increased the proportion of apoptotic cells and
      decreased the proportion of colony-forming cells as compared with untreated
      cultures. The CD40L-mediated effects were amplified following treatment with
      recombinant Fas ligand, suggesting that the effects of these ligands are
      synergistic. CD40L levels were significantly increased in long-term BM culture
      supernatants and adherent layers of BM cells from SLE patients as compared with
      controls. CONCLUSION: These data reveal a novel role for the CD40/CD40L dyad in
      SLE by demonstrating that up-regulation and induction of CD40 on BM CD34+ cells
      from patients with SLE contribute to the amplification of Fas-mediated apoptosis
      of progenitor cells.

PMID- 19180487
TI  - The emergence of antineutrophil cytoplasmic antibodies may precede the clinical
      onset of Churg-Strauss syndrome.

PMID- 19180485
TI  - Tissue targeting of anti-RNP autoimmunity: effects of T cells and myeloid
      dendritic cells in a murine model.
AB  - OBJECTIVE: To explore the role of immune cells in anti-RNP autoimmunity in a
      murine model of pneumonitis or glomerulonephritis, using adoptive transfer
      techniques. METHODS: Donor mice were immunized with 50 mug of U1-70-kd small
      nuclear RNP fusion protein and 50 mug of U1 RNA adjuvant. Whole splenocytes as
      well as CD4+ cell and dendritic cell (DC) subsets from the immunized mice were
      infused into naive syngeneic recipients. Anti-RNP and T cell responses were
      assessed by immunoblotting, enzyme-linked immunosorbent assay, and flow
      cytometry. Development of renal or lung disease was assessed by histology and
      urinalysis. RESULTS: Unfractionated splenocytes from donor mice without
      proteinuria induced predominantly lung disease in recipients (8 [57%] of 14
      versus 2 [14%] of 14 developing renal disease; P = 0.046). However, infusion of
      CD4+ cells from donors without proteinuria induced renal disease more frequently
      than lung disease (7 [70%] of 10 versus 2 [20%] of 10; P = 0.01); adoptive
      transfer of RNP+CD4+ T cells from short-term culture yielded similar results
      (renal disease in 8 [73%] of 11 recipients versus lung disease in 3 [27%] of 11).
      Cotransfer of splenic myeloid DCs and CD4+ T cells from immunized donors
      prevented induction of renal disease in all 5 recipients (P = 0.026 versus
      recipients of fresh CD4+ cells alone), although lung disease was still observed
      in 1 of 5 mice. Transfer of myeloid DCs alone from immunized donors induced lung
      disease in 3 (60%) of 5 recipients, without evidence of nephritis. Cotransfer of
      splenocytes from mice with and those without nephritis led to renal disease in 4
      of 5 recipients, without evidence of lung disease. CONCLUSION: These findings
      indicate that RNP+CD4+ T cells are sufficient to induce anti-RNP autoimmunity,
      tissue targeting in anti-RNP autoimmunity can be deviated to either a renal or
      pulmonary phenotype depending on the presence of accessory cells such as myeloid
      DCs, and DC subsets can play a role in both propagation of autoimmunity and end
      organ targeting.

PMID- 19180488
TI  - Determining the cause of isolated midline destructive lesions: comment on the
      clinical images presented by Kasifoglu et al.

PMID- 19180489
TI  - Human lupus, fewer Treg cells indeed: comment on the article by Venigalla et al.

PMID- 19180490
TI  - Different amplifying mechanisms of interleukin-17 and interferon-gamma in Fcgamma
      receptor-mediated cartilage destruction in murine immune complex-mediated
      arthritis.
AB  - OBJECTIVE: Previously, we reported that interferon-gamma (IFNgamma) aggravates
      cartilage destruction in immune complex (IC)-mediated arthritis via up-regulation
      of activating Fcgamma receptors (FcgammaR). Recently, we found that interleukin
      17 (IL-17) also aggravates cartilage destruction in arthritis models in which ICs
      are involved, but the underlying mechanism remains unknown. This study was
      undertaken to determine the role of IL-17 in FcgammaR-mediated cartilage
      destruction in IC-mediated arthritis and to compare its effect with that of
      IFNgamma. METHODS: IC-mediated arthritis was passively induced in gamma-chain(-/
      ) mice, which lack functional activating FcgammaR, and in wild-type controls.
      AdIL-17 or a control vector was injected into the knee joints 1 day prior to
      induction of IC-mediated arthritis. Knee joints were isolated for histologic
      analysis, and synovium samples were obtained for reverse transcriptase-polymerase
      chain reaction (RT-PCR). Macrophage (RAW 264.7) cell lines and polymorphonuclear
      cell (PMN; 32Dcl3) lines were stimulated with IFNgamma or IL-17 for analysis of
      FcgammaR expression using RT-PCR and fluorescence-activated cell sorting.
      RESULTS: IL-17 overexpression prior to induction of IC-mediated arthritis
      significantly aggravated cartilage destruction and inflammation, characterized by
      a massive influx of PMNs, which adhered to the cartilage surface. Although IL-17
      overexpression increased FcgammaR messenger RNA levels in the synovium, in vitro
      stimulation of macrophages and PMNs revealed that, in contrast to IFNgamma, IL-17
      did not directly regulate FcgammaR expression. Despite similar inflammation in
      AdIL-17-enhanced IC-mediated arthritis in gamma-chain(-/-) mice and wild-type
      controls, severe cartilage destruction and PMN adherence were completely absent
      in gamma-chain(-/-) mice. CONCLUSION: Our findings indicate that IL-17-mediated
      aggravation of cartilage destruction in IC-mediated arthritis is FcgammaR
      dependent. However, in contrast to IFNgamma, which directly up-regulates FcgammaR
      expression on macrophages and PMNs, IL-17 enhances cartilage destruction by
      increasing the local amount of FcgammaR-bearing neutrophils.

PMID- 19180491
TI  - Role of placenta growth factor and its receptor flt-1 in rheumatoid inflammation:
      a link between angiogenesis and inflammation.
AB  - OBJECTIVE: To investigate the direct effects of placenta growth factor (PlGF) and
      its specific receptor, flt-1, which are known to mediate angiogenesis, on the
      inflammatory process of rheumatoid arthritis (RA). METHODS: Expression of PlGF
      and flt-1 in the synovial tissue of RA patients was examined using
      immunohistochemistry. Enzyme-linked immunosorbent assay was used to determine the
      concentrations of PlGF, tumor necrosis factor alpha (TNFalpha), and interleukin-6
      (IL-6) in culture supernatants of either mononuclear cells or synoviocytes. The
      flt-1 expression level in mononuclear cells was analyzed by flow cytometry.
      Experimental arthritis was induced in mice either by immunization with type II
      collagen (CII) or by injection of anti-CII antibody. RESULTS: PlGF was highly
      expressed in the synovium of RA patients, and its primary source was fibroblast
      like synoviocytes (FLS). When stimulated with IL-1beta, FLS from RA patients
      produced higher amounts of PlGF than did FLS from patients with osteoarthritis.
      Exogenous PlGF specifically increased the production of TNFalpha and IL-6 in
      mononuclear cells from RA patients (but not those from healthy controls) via a
      calcineurin-dependent pathway. The response to PlGF was associated with increased
      expression of flt-1 on RA monocytes, which could be induced by IL-1beta and
      TNFalpha. A novel anti-flt-1 hexapeptide, GNQWFI, abrogated the PlGF-induced
      increase in TNFalpha and IL-6 production, and also suppressed CII-induced
      arthritis and serum IL-6 concentrations in mice. Moreover, genetic ablation of
      PlGF prevented the development of anti-CII antibody-induced arthritis in mice.
      CONCLUSION: Our data suggest that enhanced expression of PlGF and flt-1 may
      contribute to rheumatoid inflammation by triggering production of proinflammatory
      cytokines. The use of the novel anti-flt-1 peptide, GNQWFI, may be an effective
      strategy for the treatment of RA.

PMID- 19180492
TI  - Clinical images: beyond the classic triad: dermatologic manifestations of
      reactive arthritis.

PMID- 19180493
TI  - Modified expression of the ADAMTS enzymes and tissue inhibitor of
      metalloproteinases 3 during human intervertebral disc degeneration.
AB  - OBJECTIVE: Intervertebral disc degeneration is linked to loss of extracellular
      matrix (ECM), particularly the early loss of aggrecan. A group of
      metalloproteinases called aggrecanases are important mediators of aggrecan
      turnover. The present study was undertaken to investigate the expression of the
      recognized aggrecanases and their inhibitor, tissue inhibitor of
      metalloproteinases 3 (TIMP-3), in human intervertebral disc tissue. METHODS:
      Twenty-four nondegenerated and 30 degenerated disc samples were analyzed for
      absolute messenger RNA (mRNA) copy number of ADAMTS 1, 4, 5, 8, 9, and 15 and
      TIMP-3 by real-time reverse transcription-polymerase chain reaction. Thirty-six
      formalin-fixed embedded intervertebral disc samples of varying grades of
      degeneration were used for immunohistochemical analyses. In addition, samples
      from 8 subjects were analyzed for the presence of matrix metalloproteinase (MMP)-
      and aggrecanase-generated aggrecan products. RESULTS: Messenger RNA for all the
      aggrecanases other than ADAMTS-8 was identified in intervertebral disc tissue, as
      was mRNA for TIMP-3. Levels of mRNA expression of ADAMTS 1, 4, 5, and 15 were
      significantly increased in degenerated tissue compared with nondegenerated
      tissue. All these aggrecanases and TIMP-3 were also detected
      immunohistochemically in disc tissue, and numbers of nucleus pulposus cells
      staining positive for ADAMTS 4, 5, 9, and 15 were significantly increased in
      degenerated tissue compared with nondegenerated tissue. Aggrecan breakdown
      products generated by MMP and aggrecanase activities were also detected in
      intervertebral disc tissue. CONCLUSION: The aggrecanases ADAMTS 1, 4, 5, 9, and
      15 may contribute to the changes occurring in the ECM during intervertebral disc
      degeneration. Targeting these enzymes may be a possible future therapeutic
      strategy for the prevention of intervertebral disc degeneration and its
      associated morbidity.

PMID- 19180494
TI  - Detection of arthritis-susceptibility loci, including Ncf1, and variable effects
      of the major histocompatibility complex region depending on genetic background in
      rats.
AB  - OBJECTIVE: To characterize the arthritis-modulating effects of 3 non-major
      histocompatibility complex (MHC) quantitative trait loci (QTLs) in rat
      experimental arthritis in the disease-resistant E3 strain, and to investigate the
      disease-modulating effects of the MHC region (RT1) in various genetic
      backgrounds. METHODS: A congenic fragment containing Ncf1 along with congenic
      fragments containing the strongest remaining loci, Pia5/Cia3 and Pia7/Cia13 on
      chromosome 4, were transferred from the arthritis-susceptible DA strain into the
      background of the completely resistant E3 strain. The arthritis-regulatory
      potential of the transferred alleles was evaluated by comparing the
      susceptibility to experimental arthritis in congenic rats with that in E3 rats.
      The RT1(u) haplotype from the E3 strain was transferred into the susceptible DA
      strain (RT1(av1)), and various F(1) and F(2) hybrids were generated to assess the
      effects of RT1 on arthritis susceptibility. RESULTS: The DA allele of Ncf1 did
      not break the arthritis resistance of the E3 rats, although it led to enhanced
      autoimmune B cell responses, as indicated by significantly elevated levels of
      anticollagen antibodies in congenic rats. Introgressing Pia5 and Pia7 loci on
      chromosome 4 broke the resistance to arthritis, and the MHC locus on chromosome
      20 in DA rats enhanced arthritis when RT1 interacted with E3 genes. CONCLUSION:
      The findings in these congenic lines confirm the existence of 3 major QTLs that
      regulate the severity of arthritis and are sufficient to induce the
      transformation of a completely arthritis-resistant rat strain into an arthritis
      susceptible strain. This study also reveals a dramatic difference in the
      arthritis-regulatory potential of the rat MHC depending on genetic background,
      suggesting that strong epistatic interactions occur between MHC and non-MHC
      genes.

PMID- 19180495
TI  - Proinflammatory action of the antiinflammatory drug infliximab in tumor necrosis
      factor receptor-associated periodic syndrome.
AB  - OBJECTIVE: Tumor necrosis factor receptor (TNFR)-associated periodic syndrome
      (TRAPS) is an autosomal-dominant autoinflammatory condition caused by mutations
      in the TNFRSF1A gene. Unlike other autoinflammatory diseases in which anti-TNF
      therapy is largely a successful treatment option, therapy with the anti-TNF drug
      infliximab is often ineffective in patients with TRAPS. Moreover, in certain
      cases, infliximab actually triggers severe episodes of inflammation. The aim of
      this study was to elucidate the mechanisms underlying such a reaction. METHODS:
      Peripheral blood mononuclear cells (PBMCs) were obtained from patients with
      TRAPS. Both caspase 3 activity and NF-kappaB subunit activity were determined by
      enzyme-linked immunosorbent assay. Cytokine secretion was assessed using a
      specific customized human multiplex bead immunoassay kit. RESULTS: Unlike
      findings in controls, cells from a family of 9 patients, all of whom carried the
      T50M mutation in TNFRSF1A, failed to respond to infliximab through proapoptotic
      induction of caspase 3 activity. Instead, we observed enhanced antiapoptotic c
      Rel subunit activity, accompanied by a significant increase in secretion of the
      proinflammatory cytokines interleukin- 1beta (IL-1beta), IL-1 receptor, IL-6, IL
      8, and IL-12. CONCLUSION: Altered extracellular conformation of TNFRI, resulting
      from the T50M mutation in TNFRSF1A, results in failure of PBMCs to induce an
      apoptotic response to infliximab. We hypothesize that failure to shed infliximab
      bound TNF/TNFRI from the cell surface of cells from patients with the T50M
      mutation triggers c-Rel activation, and that this leads to a marked increase in
      cytokine secretion and an increased proinflammatory response. In light of these
      findings, we strongly advise caution when prescribing infliximab as anti-TNF
      therapy to patients with TRAPS.

PMID- 19180496
TI  - Different roles for anti-cyclic citrullinated peptide antibodies and CD4+CD28null
      cells in the acceleration of atherosclerosis in rheumatoid arthritis: comment on
      the article by Farragher et al.

PMID- 19180497
TI  - A functional polymorphism in the catechol-O-methyltransferase gene is associated
      with osteoarthritis-related pain.

PMID- 19180498
TI  - Proinflammatory role of the Th17 cytokine interleukin-22 in collagen-induced
      arthritis in C57BL/6 mice.
AB  - OBJECTIVE: To investigate the role of interleukin-22 (IL-22) in collagen-induced
      arthritis (CIA), an animal model of rheumatoid arthritis. METHODS: C57BL/6 mice
      were immunized with type II collagen (CII) in Freund's incomplete adjuvant with
      added Mycobacterium tuberculosis, and levels of IL-22 and its specific receptor,
      IL-22 receptor type I (IL-22RI), were measured in sera and tissue by enzyme
      linked immunosorbent assay and real-time quantitative polymerase chain reaction
      analysis. Clinical and histologic signs of arthritis were recorded and compared
      with those in C57BL/6 mice deficient in the IL-22 gene (IL-22(-/-)). Humoral and
      cellular immune responses against CII were analyzed. In vitro osteoclastogenesis
      assays were performed on splenocytes. RESULTS: Upon immunization with CII in
      Freund's incomplete adjuvant plus heat-killed Mycobacterium tuberculosis, sera
      from C57BL/6 mice were found to contain high levels of IL-22, and the specific IL
      22RI was expressed in lymphoid tissue, including splenocytes. IL-22(-/-) mice
      were less susceptible to CIA than were wild-type mice, as evidenced by their
      decreased incidence of arthritis and decreased pannus formation. Remarkably, the
      less severe form of arthritis in IL-22(-/-) mice was associated with increased
      production of CII-specific and total IgG antibodies, whereas cellular CII
      responses were unchanged. In vitro, IL-22 was found to promote
      osteoclastogenesis, a process that might contribute to its proinflammatory
      activity in CIA. CONCLUSION: Endogenous IL-22 plays a proinflammatory role in CIA
      in C57BL/6 mice. Our data also indicate that IL-22 promotes osteoclastogenesis
      and regulates antibody production.

PMID- 19180499
TI  - Molecular framework for response to imatinib mesylate in systemic sclerosis.
AB  - Systemic sclerosis (SSc) is an autoimmune disease in which the tyrosine kinases
      platelet-derived growth factor receptor (PDGFR) and Abl are hypothesized to
      contribute to the fibrosis and vasculopathy of the skin and internal organs.
      Herein we describe 2 patients with early diffuse cutaneous SSc (dcSSc) who
      experienced reductions in cutaneous sclerosis in response to therapy with the
      tyrosine kinase inhibitor imatinib mesylate. Immunohistochemical analyses of skin
      biopsy specimens demonstrated reductions of phosphorylated PDGFRbeta and Abl with
      imatinib therapy. By gene expression profiling, an imatinib-responsive signature
      specific to dcSSc was identified (P < 10(-8)). The response of these patients and
      the findings of the analyses suggest that PDGFRbeta and Abl play critical,
      synergistic roles in the pathogenesis of SSc, and that imatinib targets a gene
      expression program that is frequently dysregulated in dcSSc.

PMID- 19180501
TI  - Increased expression of the Akt/PKB inhibitor TRB3 in osteoarthritic chondrocytes
      inhibits insulin-like growth factor 1-mediated cell survival and proteoglycan
      synthesis.
AB  - OBJECTIVE: The chondrocyte response to insulin-like growth factor 1 (IGF-1) is
      reduced with aging and in osteoarthritis (OA). IGF-1 signals through the
      phosphatidylinositol 3-kinase/Akt pathway. TRB3, a tribbles homolog, has been
      shown to inhibit IGF-1-mediated activation of Akt in HEK 293 cells. This study
      was undertaken to determine if TRB3 is expressed in chondrocytes, and whether the
      chondrocyte response to IGF-1 is reduced by TRB3. METHODS: Human articular
      cartilage was obtained from normal tissue donors and from patients with OA at the
      time of knee replacement surgery. TRB3 was assessed in the tissue samples by
      reverse transcription-polymerase chain reaction, immunoblotting, and
      immunohistochemistry. Overexpression of TRB3 was induced by transient
      transfection to determine the effects of TRB3 on cell survival and proteoglycan
      synthesis. RESULTS: TRB3 messenger RNA was detected in normal human chondrocytes.
      TRB3 protein levels were low in cells from normal cartilage but significantly
      increased in cells from OA cartilage. Incubation with 2 agents that induce
      endoplasmic reticulum stress, tunicamycin and thapsigargin, increased TRB3 levels
      in normal cells. Overexpression of TRB3 inhibited Akt phosphorylation and reduced
      chondrocyte survival and proteoglycan synthesis. CONCLUSION: These results are
      the first to demonstrate that TRB3 is present in human chondrocytes, and that the
      level of TRB3 is increased in OA cartilage and in isolated OA chondrocytes.
      Because it is an inhibitor of Akt activation, elevated TRB3 production could play
      a role in the increased cell death and reduced response to IGF-1 observed in OA
      cartilage.

PMID- 19180500
TI  - The NOD2 defect in Blau syndrome does not result in excess interleukin-1
      activity.
AB  - OBJECTIVE: Blau syndrome is a rare, autosomal-dominant, autoinflammatory disorder
      characterized by granulomatous arthritis, uveitis, and dermatitis. Genetics
      studies have shown that the disease is caused by single nonsynonymous
      substitutions in NOD-2, a member of the NOD-like receptor or NACHT-leucine-rich
      repeat (NLR) family of intracellular proteins. Several NLRs function in the
      innate immune system as sensors of pathogen components and participate in immune
      mediated cellular responses via the caspase 1 inflammasome. Mutations in a gene
      related to NOD-2, NLRP3, are responsible for excess caspase 1-dependent
      interleukin-1beta (IL-1beta) in cryopyrinopathies such as Muckle-Wells syndrome.
      Furthermore, functional studies demonstrate that caspase 1-mediated release of IL
      1beta also involves NOD-2. The aim of this study was to test the hypothesis that
      IL-1beta may mediate the inflammation seen in patients with Blau syndrome.
      METHODS: IL-1beta release was measured in peripheral blood mononuclear cells
      cultured in vitro, obtained from 5 Blau syndrome individuals with a NOD2 (CARD15)
      mutation. RESULTS: We observed no evidence for increased IL-1beta production in
      cells obtained from subjects with Blau syndrome compared with healthy control
      subjects. Furthermore, we presented 2 cases of Blau syndrome in which recombinant
      human IL-1 receptor antagonist (anakinra) was ineffective treatment. CONCLUSION:
      Taken together, these data suggest that in contrast to related IL-1beta-dependent
      autoinflammatory cryopyrinopathies, Blau syndrome is not mediated by excess IL
      1beta or other IL-1 activity.

PMID- 19180502
TI  - Expression, regulation, and signaling of the pattern-recognition receptor
      nucleotide-binding oligomerization domain 2 in rheumatoid arthritis synovial
      fibroblasts.
AB  - OBJECTIVE: Since pattern-recognition receptors (PRRs), in particular Toll-like
      receptors (TLRs), were found to be overexpressed in the synovium of rheumatoid
      arthritis (RA) patients and to play a role in the production of disease-relevant
      molecules, we sought to determine the expression, regulation, and function of the
      PRR nucleotide-binding oligomerization domain 2 (NOD-2) in RA. METHODS:
      Expression of NOD-2 in synovial tissues was analyzed by immunohistochemistry.
      Expression and induction of NOD-2 in RA synovial fibroblasts (RASFs) were
      measured by conventional and real-time polymerase chain reaction (PCR) analyses.
      Levels of interleukin-6 (IL-6) and IL-8 were measured by enzyme-linked
      immunosorbent assay (ELISA) and expression of matrix metalloproteinases (MMPs) by
      ELISA and/or real-time PCR. NOD-2 expression was silenced with small interfering
      RNA. Western blotting with antibodies against phosphorylated and total p38, JNK,
      and ERK, as well as inhibitors of p38, JNK, and ERK was performed. Activation of
      NF-kappaB was measured by electrophoretic mobility shift assay. RESULTS: NOD-2
      was expressed by fibroblasts and macrophages in the synovium of RA patients,
      predominantly at sites of invasion into articular cartilage. In cultured RASFs,
      no basal expression of messenger RNA for NOD-2 was detectable, but was induced by
      poly(I-C), lipopolysaccharide, and tumor necrosis factor alpha. After up
      regulation of NOD-2 by TLR ligands, its ligand muramyl dipeptide (MDP) increased
      the expression of IL-6 and IL-8 via p38 and NF-kappaB. Stimulation with MDP
      further induced the expression of MMP-1, MMP-3, and MMP-13. CONCLUSION: Not only
      TLRs, but also the PRR NOD-2 is expressed in the synovium of RA patients, and
      activation of NOD-2 acts synergistically with TLRs in the production of
      proinflammatory and destructive mediators. Therefore, NOD-2 might contribute to
      the initiation and perpetuation of chronic, destructive inflammation in RA.

PMID- 19180503
TI  - Pain and rheumatology: thinking outside the joint.

PMID- 19180504
TI  - Clinical images: Otitis media and nasal granulation in Wegener's granulomatosis.

PMID- 19180505
TI  - Unity in the field of rheumatology: the role of the ACR.

PMID- 19180510
TI  - Alteration of articular cartilage frictional properties by transforming growth
      factor beta, interleukin-1beta, and oncostatin M.
AB  - OBJECTIVE: To evaluate the functional effects of transforming growth factor beta1
      (TGFbeta1), interleukin-1beta (IL-1beta), and oncostatin M (OSM) on the
      frictional properties of articular cartilage and to determine the role of
      cytokine-mediated changes in cartilage frictional properties by extracting and
      redepositing lubricin on the surface of cartilage explants. METHODS: Neonatal
      bovine cartilage explants were cultured in the presence or absence of 10 ng/ml of
      TGFbeta1, IL-1beta, or OSM over 48 hours. Boundary lubrication tests were
      conducted to determine the effects of endogenously produced surface localized
      lubricin and of exogenous lubricin at the tissue surface and in the lubricant
      solution. The initial friction coefficient (micro(0)), equilibrium friction
      coefficient (micro(eq)), and Young's modulus (E(Y)) were determined from the
      temporal load data. RESULTS: IL-1beta and OSM decreased tissue glycosaminoglycan
      (GAG) content by approximately 20% over 48 hours and decreased E(Y) to a similar
      extent (11-17%), but TGFbeta did not alter GAG content or E(Y). Alterations in
      proteoglycan content corresponded to changes in micro(0), but endogenous lubricin
      decreased boundary mode micro(eq). The addition of exogenous lubricin, either
      localized at the tissue surface or in the lubricating solution, did not modulate
      micro(0), but it did lower micro(eq) in cytokine-treated cartilage. CONCLUSION:
      This study provides new insight into the functional consequences of cytokine
      mediated changes in friction coefficient. In combination with established
      pathways of cytokine-mediated lubricin metabolism, these data provide evidence of
      distinct biochemical origins of boundary and biphasic pressure-mediated
      lubrication mechanisms in cartilage, with boundary lubrication regulated by
      surface accumulation of lubricants and biphasic lubrication controlled by factors
      such as GAG content that affect water movement through the tissue.

PMID- 19180509
TI  - Prostaglandin E2 and its cognate EP receptors control human adult articular
      cartilage homeostasis and are linked to the pathophysiology of osteoarthritis.
AB  - OBJECTIVE: To elucidate the pathophysiologic links between prostaglandin E(2)
      (PGE(2)) and osteoarthritis (OA) by characterizing the catabolic effects of
      PGE(2) and its unique receptors in human adult articular chondrocytes. METHODS:
      Human adult articular chondrocytes were cultured in monolayer or alginate beads
      with and without PGE(2) and/or agonists of EP receptors, antagonists of EP
      receptors, and cytokines. Cell survival, proliferation, and total proteoglycan
      synthesis and accumulation were measured in alginate beads. Chondrocyte-related
      gene expression and phosphatidylinositol 3-kinase/Akt signaling were assessed by
      real-time reverse transcription-polymerase chain reaction and Western blotting,
      respectively, using a monolayer cell culture model. RESULTS: Stimulation of human
      articular chondrocytes with PGE(2) through the EP2 receptor suppressed
      proteoglycan accumulation and synthesis, suppressed aggrecan gene expression, did
      not appreciably affect expression of matrix-degrading enzymes, and decreased the
      type II collagen:type I collagen ratio. EP2 and EP4 receptors were expressed at
      higher levels in knee cartilage than in ankle cartilage and in a grade-dependent
      manner. PGE(2) titration combined with interleukin-1 (IL-1) synergistically
      accelerated expression of pain-associated molecules such as inducible nitric
      oxide synthase and IL-6. Finally, stimulation with exogenous PGE(2) or an EP2
      receptor-specific agonist inhibited activation of Akt that was induced by insulin
      like growth factor 1. CONCLUSION: PGE(2) exerts an antianabolic effect on human
      adult articular cartilage in vitro, and EP2 and EP4 receptor antagonists may
      represent effective therapeutic agents for the treatment of OA.

PMID- 19180511
TI  - Unmasking of a protective tumor necrosis factor receptor I-mediated signal in the
      collagen-induced arthritis model.
AB  - OBJECTIVE: To examine the relative importance of tumor necrosis factor receptor I
      (TNFRI) signaling in the hematopoietic tissue compartment in the progression of
      collagen-induced arthritis (CIA), a model of rheumatoid arthritis (RA). METHODS:
      DBA/1 mice were administered a lethal radiation dose and were then rescued with
      bone marrow derived from either DBA/1 or TNFRI(-/-) mice. CIA was then induced,
      and disease progression was characterized. RESULTS: Surprisingly, mice with CIA
      that received TNFRI(-/-) donor marrow developed increased disease severity as
      compared with control mice with CIA. This could not be attributed to an increased
      primary response to collagen or to the contribution of a non-DBA genetic
      background. In mice that received TNFRI(-/-) bone marrow, histologic markers of
      advanced disease were evident shortly after initiation of the immune response to
      collagen and long before clinical evidence of disease. Serum TNFalpha was
      undetectable, whereas serum interleukin-12 p40 levels were increased, at the end
      point of the study in mice that received TNFRI(-/-) bone marrow. CONCLUSION:
      These data raise the intriguing possibility of the existence of an
      antiinflammatory, TNFRI-mediated circuit in the hematopoietic compartment. This
      circuit bears a resemblance to the switch in TNFalpha function that has been
      observed during the resolution of bacterial infections. These data suggest that
      TNFRI-mediated signals in the radioresistant tissues contribute to disease
      progression, whereas TNFRI-mediated signals in the radiosensitive tissues can
      contribute to protection from disease. We thus put forward the hypothesis that
      the degree of response to TNFalpha blockade in RA is dependent in part on the
      relative genetic strengths of these 2 pathways.

PMID- 19180512
TI  - HLA-E gene polymorphism associated with susceptibility to Kawasaki disease and
      formation of coronary artery aneurysms.
AB  - OBJECTIVE: Kawasaki disease (KD) is a pediatric systemic vasculitis of unknown
      cause for which a genetic influence is supposed. The purpose of this study was to
      identify possible genetic variants in the major histocompatibility complex (MHC)
      region that are associated with KD and the development of coronary artery
      aneurysms (CAAs) in a Taiwanese population. METHODS: The 168 genetic variants
      covering the MHC locus were analyzed in an association study of a Taiwanese
      cohort of 93 KD patients and 680 unrelated healthy children matched for sex and
      age with the study patients. RESULTS: Eleven single-nucleotide polymorphisms
      (SNPs) were associated with the occurrence of KD. The SNP located at the 3'
      untranslated region of HLA-E (rs2844724) was highly associated (P < 1 x 10(-7)).
      In addition, the frequency of the C allele was higher in KD patients without CAAs
      than in controls (P < 0.001) due to a significantly increased frequency of the CC
      and CT genotypes. Plasma levels of soluble HLA-E were significantly higher in KD
      patients than in controls regardless of the presence of CAAs. Furthermore, there
      was a trend toward higher plasma levels of soluble HLA-E in KD patients with the
      CT and TT genotypes of the HLA-E gene polymorphism. CONCLUSION: Our results
      suggest that the HLA-E gene polymorphism may play a role in the pathogenesis of
      KD.

PMID- 19180513
TI  - beta2-glycoprotein i is a cofactor for tissue plasminogen activator-mediated
      plasminogen activation.
AB  - OBJECTIVE: Regulation of the conversion of plasminogen to plasmin by tissue
      plasminogen activator (tPA) is critical in the control of fibrin deposition.
      While several plasminogen activators have been described, soluble plasma
      cofactors that stimulate fibrinolysis have not been characterized. The purpose of
      this study was to investigate the effects of beta(2)-glycoprotein I (beta(2)GPI),
      an abundant plasma glycoprotein, on tPA-mediated plasminogen activation. METHODS:
      The effect of beta(2)GPI on tPA-mediated activation of plasminogen was assessed
      using amidolytic assays, a fibrin gel, and plasma clots. Binding of beta(2)GPI to
      tPA and plasminogen was determined in parallel. The effects of IgG fractions and
      anti-beta(2)GPI antibodies from patients with antiphospholipid syndrome (APS) on
      tPA-mediated plasminogen activation were also measured. RESULTS: Beta(2)
      glycoprotein I stimulated tPA-dependent plasminogen activation in the fluid phase
      and within a fibrin gel. The beta(2)GPI region responsible for stimulating tPA
      activity was shown to be at least partly contained within beta(2)GPI domain V. In
      addition, beta(2)GPI bound tPA with high affinity (K(d) approximately 20 nM),
      stimulated tPA amidolytic activity, and caused an overall 20-fold increase in the
      catalytic efficiency (K(cat)/K(m)) of tPA-mediated conversion of Glu-plasminogen
      to plasmin. Moreover, depletion of beta(2)GPI from plasma led to diminished rates
      of clot lysis, with restoration of normal lysis rates following beta(2)GPI
      repletion. Stimulation of tPA-mediated plasminogen activity by beta(2)GPI was
      inhibited by monoclonal anti-beta(2)GPI antibodies as well as by anti-beta(2)GPI
      antibodies from patients with APS. CONCLUSION: These findings suggest that
      beta(2)GPI may be an endogenous regulator of fibrinolysis. Impairment of
      beta(2)GPI-stimulated fibrinolysis by anti-beta(2)GPI antibodies may contribute
      to the development of thrombosis in patients with APS.

PMID- 19180514
TI  - Inhibition of p38: has the fat lady sung?

PMID- 19180515
TI  - In vitro stage-specific chondrogenesis of mesenchymal stem cells committed to
      chondrocytes.
AB  - OBJECTIVE: Osteoarthritis is characterized by an imbalance in cartilage
      homeostasis, which could potentially be corrected by mesenchymal stem cell (MSC)
      based therapies. However, in vivo implantation of undifferentiated MSCs has led
      to unexpected results. This study was undertaken to establish a model for
      preconditioning of MSCs toward chondrogenesis as a more effective clinical tool
      for cartilage regeneration. METHODS: A coculture preconditioning system was used
      to improve the chondrogenic potential of human MSCs and to study the detailed
      stages of chondrogenesis of MSCs, using a human MSC line, Kp-hMSC, in commitment
      cocultures with a human chondrocyte line, hPi (labeled with green fluorescent
      protein [GFP]). In addition, committed MSCs were seeded into a collagen scaffold
      and analyzed for their neocartilage-forming ability. RESULTS: Coculture of hPi
      GFP chondrocytes with Kp-hMSCs induced chondrogenesis, as indicated by the
      increased expression of chondrogenic genes and accumulation of chondrogenic
      matrix, but with no effect on osteogenic markers. The chondrogenic process of
      committed MSCs was initiated with highly activated chondrogenic adhesion
      molecules and stimulated cartilage developmental growth factors, including
      members of the transforming growth factor beta superfamily and their downstream
      regulators, the Smads, as well as endothelial growth factor, fibroblast growth
      factor, insulin-like growth factor, and vascular endothelial growth factor.
      Furthermore, committed Kp-hMSCs acquired neocartilage-forming potential within
      the collagen scaffold. CONCLUSION: These findings help define the molecular
      markers of chondrogenesis and more accurately delineate the stages of
      chondrogenesis during chondrocytic differentiation of human MSCs. The results
      indicate that human MSCs committed to the chondroprogenitor stage of chondrocytic
      differentiation undergo detailed chondrogenic changes. This model of in vitro
      chondrogenesis of human MSCs represents an advance in cell-based transplantation
      for future clinical use.

PMID- 19180516
TI  - Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor,
      in a double-blind, methotrexate-controlled study of patients with active
      rheumatoid arthritis.
AB  - OBJECTIVE: To determine the efficacy and safety of pamapimod (a selective
      inhibitor of the alpha-isoform of p38 MAP kinase) as monotherapy in comparison
      with methotrexate (MTX) treatment in adult patients with active rheumatoid
      arthritis (RA). METHODS: Patients were randomly assigned to 1 of 4 treatment
      groups and received 12 weeks of double-blind treatment. One group received MTX
      (7.5 mg/week with planned escalation to 20 mg/week), and 3 groups received
      pamapimod (50, 150, or 300 mg) once daily. The primary efficacy end point was the
      proportion of patients meeting the American College of Rheumatology 20%
      improvement criteria (achieving an ACR20 response) at 12 weeks. Secondary end
      points included ACR50 and ACR70 responses, change from baseline in the Disease
      Activity Score in 28 joints (DAS28), categorical analyses of DAS28/European
      League Against Rheumatism response, and change from baseline in each parameter of
      the ACR core set of measures. Safety monitoring included recording of adverse
      events (AEs), laboratory testing, immunology assessments, administration of
      electrocardiograms, and assessment of vital signs. RESULTS: Patients assigned to
      receive MTX and pamapimod had similar demographics and baseline characteristics.
      At week 12, fewer patients taking pamapimod had an ACR20 response (23%, 18%, and
      31% in the 50-, 150-, and 300-mg groups, respectively) compared with patients
      taking MTX (45%). Secondary efficacy end points showed a similar pattern. AEs
      were typically characterized as mild and included infections, skin disorders, and
      dizziness. Pamapimod was generally well tolerated, but the 300-mg dose appeared
      to be more toxic than either the 2 lower doses or MTX. CONCLUSION: The present
      results showed that pamapimod was not as effective as MTX in the treatment of
      active RA.

PMID- 19180517
TI  - Survival in pulmonary hypertension associated with the scleroderma spectrum of
      diseases: impact of interstitial lung disease.
AB  - OBJECTIVE: Pulmonary hypertension (PH) is an important cause of mortality in
      systemic sclerosis (SSc), where it can be isolated (pulmonary arterial
      hypertension [PAH]) or associated with interstitial lung disease (ILD). This
      study was undertaken to characterize determinants of survival among SSc patients
      with either type of PH who received PAH-specific therapy. METHODS: Consecutive
      SSc patients with PAH or ILD-associated PH confirmed by right heart
      catheterization were included in the study. Kaplan-Meier and Cox proportional
      hazards models were used to compare survival between SSc patients with PAH and
      those with ILD-associated PH and to identify predictors of survival. RESULTS:
      Fifty-nine patients (39 with PAH and 20 with ILD-associated PH) were identified.
      The majority (15 of 20 with ILD-associated PH and 27 of 39 with PAH) received an
      endothelin receptor antagonist as initial therapy. Median followup time was 4.4
      years (range 2.7-7.4 years). Survival was significantly worse in SSc patients
      with ILD-associated PH than in those with PAH (1-, 2-, and 3-year survival rates
      82%, 46%, and 39% versus 87%, 79%, and 64%, respectively; P < 0.01 by log rank
      test). In a multivariable analysis, ILD-associated PH was associated with a 5
      fold increase in risk of death compared with PAH. Pulmonary vascular resistance
      index was also an independent predictor of mortality in the overall cohort
      (hazard ratio 1.05, P < 0.01) and was a significant univariable risk factor in
      each group separately. Type of initial PAH therapy and the use of warfarin were
      not related to survival. CONCLUSION: Survival in SSc complicated by PH remains
      poor despite currently available treatment options. While therapy may be
      associated with improved survival in PAH compared with historical controls, the
      prognosis for patients with ILD-associated PH is particularly grim. Early
      diagnosis and treatment may improve outcomes since worsening hemodynamic factors
      were associated with reduced survival.

PMID- 19180518
TI  - Associations of 25 structural, degradative, and inflammatory candidate genes with
      lumbar disc desiccation, bulging, and height narrowing.
AB  - OBJECTIVE: To examine the allelic diversity of structural, inflammatory, and
      matrix-modifying gene candidates and their association with disc degeneration.
      METHODS: Subjects were 588 men ages 35-70 years. We investigated associations of
      single-nucleotide polymorphisms in AGC1 and in 12 collagen, 8 interleukin, and 4
      matrix metalloproteinase genes with quantitative magnetic resonance imaging
      measurements of disc desiccation and disc bulging and height narrowing scores,
      after controlling for age and suspected risk factors. Analyses were performed
      using QTDT software. P values were derived from 1,000 permutations, and empirical
      P values for global significance also were applied. RESULTS: Twelve of the 99
      variants in 25 selected candidate genes provided evidence of association (P <
      0.05) with disc signal intensity in the upper and/or lower lumbar regions.
      Allelic variants of AGC1 (rs1042631; P = 0.001), COL1A1 (rs2075555; P = 0.005),
      COL9A1 (rs696990; P = 0.00008), and COL11A2 (rs2076311; P = 0.018) genes provided
      the most significant evidence of association with disc signal intensity. The same
      variants of AGC1 (P = 0.010) and COL9A1 (P = 0.014), as well as variants in the
      COL11A1 gene (rs1463035 [P = 0.004]; rs1337185 [P = 0.015]) were also associated
      with disc bulging, as was AGC1 with disc height narrowing (rs1516797; P = 0.005).
      In addition, 4 allelic variants in the immunologic candidate genes (rs2071375 in
      IL1A [P = 0.027]; rs1420100 in IL18RAP [P = 0.005]) were associated with disc
      signal intensity. CONCLUSION: Genetic variants account for interindividual
      differences in disc matrix synthesis and degradation. The accuracy of the
      quantitative disc signal intensity measurements we used likely enhanced our
      ability to observe these associations. Our findings shed light on possible
      mechanisms of degeneration and support the view that disc degeneration is a
      polygenetic condition.

PMID- 19180519
TI  - Inference on treatment effects for targeted clinical trials under enrichment
      design.
AB  - After completion of a human genome project, the disease targets at molecular
      level can be identified. As a result, treatment modality for molecular targets
      can be developed. In practice, targeted clinical trials are usually conducted for
      evaluation of the possibility and feasibility of the individualized treatment of
      patients. However, the accuracy of diagnostic devices for identification of such
      molecular targets is usually not perfect. Therefore, some of the patients
      enrolled in targeted clinical trials with a positive result by the diagnostic
      device might not have the specific molecular targets and hence the treatment
      effects of the targeted drugs estimated from targeted clinical trials could be
      biased for the patient population truly with the molecular targets. Under an
      enrichment design for targeted clinical trials, we propose to use the EM
      algorithm and bootstrap method for obtaining the inference of the treatment
      effects of the targeted drugs in the patient population truly with molecular
      targets. A simulation study was conducted to empirically investigate the bias and
      variability of the proposed estimator and the size and power of the proposed
      testing method. Simulation results demonstrate that the proposed estimator is
      unbiased with adequate precision and the confidence interval can provide
      satisfactory coverage probability. In addition, the proposed testing procedure
      can adequately control the size with sufficient power. A practical example
      illustrates the utility of the proposed method.

PMID- 19180520
TI  - Back to basics: explaining sample size in outcome trials, are statisticians doing
      a thorough job?
AB  - Time to event outcome trials in clinical research are typically large, expensive
      and high-profile affairs. Such trials are commonplace in oncology and
      cardiovascular therapeutic areas but are also seen in other areas such as
      respiratory in indications like chronic obstructive pulmonary disease. Their
      progress is closely monitored and results are often eagerly awaited. Once
      available, the top line result is often big news, at least within the therapeutic
      area in which it was conducted, and the data are subsequently fully scrutinized
      in a series of high-profile publications. In such circumstances, the statistician
      has a vital role to play in the design, conduct, analysis and reporting of the
      trial. In particular, in drug development it is incumbent on the statistician to
      ensure at the outset that the sizing of the trial is fully appreciated by their
      medical, and other non-statistical, drug development team colleagues and that the
      risk of delivering a statistically significant but clinically unpersuasive result
      is minimized. The statistician also has a key role in advising the team when,
      early in the life of an outcomes trial, a lower than anticipated event rate
      appears to be emerging. This paper highlights some of the important features
      relating to outcome trial sample sizing and makes a number of simple
      recommendations aimed at ensuring a better, common understanding of the interplay
      between sample size and power and the final result required to provide a
      statistically positive and clinically persuasive outcome.

PMID- 19180521
TI  - Conformational requirement on peptides to exert laminin's activities and search
      for protein segments with laminin's activities.
AB  - The human laminin alpha3 chain LG4 module has biological activities of cell
      adhesion, heparin binding, migration, and neurite outgrowth. The authors had
      previously identified that the active site of this protein is in residues 1411
      1429 (amino-acid sequence = KNSFMALYLSKGRLVFALG called A3G756) and that a three
      amino-acid sequence KGR in A3G756 is crucial for exerting the activities. An
      experiment has shown that a cyclo-hEF3A peptide (a cyclic analog of A3G756)
      exhibits stronger activities than a linear-hEF3A peptide (a linearized peptide of
      the cyclo-hEF3A peptide). This experiment implies that adopting a loop
      conformation may be important for exerting the activities. In this study, the
      authors first computed the solution structures of the cyclo-hEF3A and linear
      hEF3A peptides by molecular dynamics simulations. The obtained conformational
      ensembles consisted of a variety of conformations, which is a usual property of
      short peptides in solution. The ensembles involved a fraction where the peptide
      adopted beta-hairpins and KGR was located at the hairpin head. If there are
      protein segments that adopt beta-hairpins similar to those sampled from the
      simulation and have the KGR sequence at the hairpin head, these segments may have
      some activities. Then, the authors searched a database for segments satisfying
      these requirements and detected six functional segments. Three of them had
      laminin's activity, and the remaining three had activities similar to laminin's
      activities. Analyses on the conformational ensembles of cyclo- and linear-hEF3A
      peptides suggest that not only the KGR position in the hairpin but also the inter
      strand packing is important for exerting laminin's activities.

PMID- 19180522
TI  - An engineering, multiscale constitutive model for fiber-forming collagen in
      tension.
AB  - This work proposes a nonlinear constitutive model for a single collagen fiber.
      Fiber-forming collagen can exhibit different hierarchies of basic units, called
      fascicles, bundles, fibrils, microfibrils, and so forth, down to the molecular
      (tropocollagen) level. Exploiting the fact that at each hierarchy level the
      microstructure can be seen, at least approximately, as that of a wavy, or
      crimped, extensible cable, the proposed stress-strain model considers a given
      number of levels, each of which contributes to the overall mechanical behavior
      according to its own geometrical features (crimp, or waviness), as well as to the
      basic mechanical properties of the tropocollagen. The crimp features at all
      levels are assumed to be random variables, whose statistical integration
      furnishes a stress-strain curve for a collagen fiber. The soundness of this model
      the first, to the Authors' knowledge, to treat a single collagen fiber as a
      microstructured nonlinear structural element-is checked by its application to
      collagen fibers for which experimental results are available: rat tail tendon,
      periodontal ligament, and engineered ones. Here, no attempt is made to obtain a
      stress-strain law for generic collagenous tissues, which exhibit specific
      features, often much more complex than those of a single fiber. However, it is
      trivial to observe that the availability of a sound, microstructurally based
      constitutive law for a single collagen fiber (but applicable at any sub-level, or
      to any other material with a similar microstructure) is essential for assembling
      complex constitutive models for any collagenous fibrous tissue.

PMID- 19180523
TI  - Electrostatic surface charge acceleration of bone ingrowth of porous
      hydroxyapatite/beta-tricalcium phosphate ceramics.
AB  - Bone ingrowth enhancement by the surface induced charges of the electrically
      polarized hydroxyapatite (HA)/beta-tricalcium phosphate (beta-TCP) ceramics was
      histologically investigated to clarify the early stage events of ossification.
      The HA/beta-TCP specimens with a relatively low porosity of 45% for bone ingrowth
      were polarized in a dc electric field at 400 degrees C for 1 h. The large
      preserved charges of 8 muC cm(-2) significantly promoted the bone ingrowth
      process of the porous ceramics implanted in femoral diaphyses of New Zealand
      white rabbits. The bone formation in the pores of the polarized HA/beta-TCP
      specimens was observed within 1 week after surgery. The bone occupancy of the
      polarized HA/beta-TCP pores reached more than 90% at as early as 2 weeks and
      significantly higher than that of the nonpolarized. The electrical polarization
      was proved to be effective for bone penetration improvement of low porosity
      ceramics. The electrically polarized HA/beta-TCP bone grafts with a lower
      porosity and a higher mechanical strength combined high osteoconductivity
      generated by the induced surface charges.

PMID- 19180524
TI  - Enhanced bone formation by marrow-derived endothelial and osteogenic cell
      transplantation.
AB  - Bone marrow-derived osteogenic cells can regenerate bone tissuesin vivo. The aim
      of the present study is to determine whether the cotransplantation of bone marrow
      derived endothelial-like cells (BMECs) enhances bone regeneration by bone marrow
      derived osteogenic cell (BMOC) transplantation in osseous defects. Canine bone
      marrow cells were differentiated separately into BMECs and BMOCs. Using apatite
      coated poly(lactide-co-glycolide)/hydroxyapatite composite scaffolds as cell
      delivery vehicles, BMOCs were transplanted with or without BMECs into critical
      sized calvarial defects in immunodeficient mice. Histological analyses,
      microcomputed tomography, and soft X-ray were performed to assess mineralized
      bone formation at 8 weeks. Cotransplantation of BMECs and BMOCs resulted in
      greater bone formation than transplantation of BMOCs alone. There was a
      significant (p < 0.05) increase in bone formation area following
      cotransplantation (30.8% +/- 2.5%), compared with transplantation of BMOCs alone
      (15.3% +/- 1.9%). These results demonstrate that the cotransplantation of BMECs
      enhances bone regeneration mediated by BMOC transplantation in osseous defects.

PMID- 19180525
TI  - Preparation of hydroxyapatite-titania hybrid coatings on titanium alloy.
AB  - Hydroxypapatite-titania hybrid films on Ti6Al4V alloys were prepared by sol-gel
      technique by incorporating presynthesized hydroxypapatite
      (Ca(10)(PO(4))(6)(OH)(2) or HAp) powders into a titanium-alkoxide dip coating
      solution. Titania network was formed by the hydrolysis and condensation of Ti
      isopropoxide Ti[OCH(CH(3))(2)](4)-based sols. The effect of titania sol
      formulation, specifically the effect of organic solvents on the microstructure of
      the dip coated films calcined at 500 degrees C has been investigated. The
      coatings exhibit higher tendency for cracking when a high vapor pressure solvent,
      such as ethanol (C(2)H(5)OH) is used causing development of higher macroscopic
      stresses during evaporation of the sol. Titania sol formulations replacing the
      solvent with n-proponal (CH(3)(CH(2))(2)OH) and acetly-acetone (C(5)H(8)O)
      combinations enhanced the microstructural integrity of the coating during
      evaporation and calcination treatments. Sol-gel processing parameters, such as
      multilayer coating application and withdrawal rate, can be employed to change the
      titania thickness in the range of 0.120-1.1 microm and to control the
      microstructure of HAp-titania hybrid coatings. A high-calcination temperature in
      the range of 400-600 degrees C does not cause a distinct change in crystals
      nature of the titania matrix or HAp, but results in more cracking due to the
      combined effect of densification originated stresses and thermal stresses upon
      cooling. Slower withdraw rates and multilayer dip coating lead to coatings more
      vulnerable to microcracking.

PMID- 19180526
TI  - Development of a biomimetic collagen-hydroxyapatite scaffold for bone tissue
      engineering using a SBF immersion technique.
AB  - The objective of this study was to develop a biomimetic, highly porous collagen
      hydroxyapatite (HA) composite scaffold for bone tissue engineering (TE),
      combining the biological performance and the high porosity of a collagen scaffold
      with the high mechanical stiffness of a HA scaffold. Pure collagen scaffolds were
      produced using a lyophilization process and immersed in simulated body fluid
      (SBF) to provide a biomimetic coating. Pure collagen scaffolds served as a
      control. The mechanical, material, and structural properties of the scaffolds
      were analyzed and the biological performance of the scaffolds was evaluated by
      monitoring the cellular metabolic activity and cell number at 1, 2, and 7 days
      post seeding. The SBF-treated scaffolds exhibited a significantly increased
      stiffness compared to the pure collagen group (4-fold increase), while a highly
      interconnected structure (95%) was retained. FTIR indicated that the SBF coating
      exhibited similar characteristics to pure HA. Micro-CT showed a homogeneous
      distribution of HA. Scanning electron microscopy also indicated a mineralization
      of the collagen combined with a precipitation of HA onto the collagen. The
      excellent biological performance of the collagen scaffolds was maintained in the
      collagen-HA scaffolds as demonstrated from cellular metabolic activity and total
      cell number. This investigation has successfully developed a biomimetic collagen
      HA composite scaffold. An increase in the mechanical properties combined with an
      excellent biological performance in vitro was observed, indicating the high
      potential of the scaffold for bone TE.

PMID- 19180527
TI  - The effect of nucleus implant parameters on the compressive mechanics of the
      lumbar intervertebral disc: a finite element study.
AB  - A simplified finite element model of the human lumbar intervertebral disc was
      utilized for understanding nucleus pulposus implant mechanics. The model was used
      to assess the effect of nucleus implant parameter variations on the resulting
      compressive biomechanics of the lumbar anterior column unit. The effects of
      nucleus implant material (modulus and Poisson's ratio) and geometrical (height
      and diameter) parameters on the mechanical behavior of the disc were
      investigated. The model predicted that variations in implant modulus contribute
      less to the compressive disc mechanics compared to the implant geometrical
      parameters, for the ranges examined. It was concluded that some threshold exists
      for the nucleus implant modulus, below which little variations in load
      displacement behavior were shown. Compressive biomechanics were highly affected
      by implant volume (under-filling the nucleus cavity, line-to-line fit, or over
      filling the nucleus cavity) with a greater restoration of compressive mechanics
      observed with the over-filled implant design. This work indicated the effect of
      nucleus implant parameter variations on the compressive mechanics of the human
      lumbar intervertebral disc and importance of the "fit and fill" effect of the
      nuclear cavity in the restoration of the human intervertebral disc mechanics in
      compression. These findings may have clinical significance for nucleus implant
      design.

PMID- 19180528
TI  - Ecomorphology of morpho-functional relationships in the family of Sparidae: a
      quantitative statistic approach.
AB  - In many fish species, morphological similarity can be considered as a proxy for
      similarities in habitat use. The Sparidae family includes species that are
      recognized for common morphological features such as structure and positioning of
      the fins and specialized dentition. The aim of this study was to quantitatively
      describe the relationship of body shape morphology with habitat use, trophic
      level, and systematics in the majority of known Sparidae species (N = 92). This
      ecomorphological comparison was performed with a geometric morphometric approach
      considering as variables the Trophic Index (TROPH), the habitat (i.e., classified
      as demersal, benthopelagic and reef associated) and the phylogenetic relationship
      of species at the subfamily level. The analysis by the TROPH variable showed a
      positive relation with shape because the morphological features of all the
      species are strongly correlated with their trophic behavior (e.g., herbivore
      species have a smaller mouth gap that make them able to feed upon sessile
      resources). The morphological analysis according to the Habitat variable was used
      to classify species according to a feeding-habitat niche in terms of portion of
      the water column and seabed space where species mostly perform their behavioral
      activities. We described three kinds of morphological designs in relation to a
      benthopelagic, demersal and reef-associated habit. The six subfamily groups were
      morphologically well distinguishable and the cladogram relative to Mahalanobis'
      morphological distances was compared with those proposed by other authors. We
      also quantified the phylogenetic relationship among the different subfamilies
      based on the analysis of shape in relation to trophic ecology, confirming the
      observations of the authors.

PMID- 19180529
TI  - The BRCA Self-Concept Scale: a new instrument to measure self-concept in BRCA1/2
      mutation carriers.
AB  - Genetic testing for BRCA1/2 has psychosocial impacts including those related to
      views of personal health, sense of self and identity and body image. The
      centrality of a person's self-concept in maintaining physical and psychosocial
      well-being has been well recognized; however, to date research exploring altered
      self-concept related to carrier knowledge is limited. OBJECTIVE: The objective of
      the study was to develop and validate a scale to measure the self-concept among
      individuals testing positive for BRCA1/2 mutations. METHODS: The study was
      conducted in two phases: phase I: item generation and refinement and phase II:
      scale selection and initial validation. During phase I, scale items were
      generated through individual interviews and focus groups of women with BRCA1/2
      mutations, including women with or without a prior diagnosis of cancer. In phase
      II items were selected based on several criteria resulting in a 25-item scale,
      which underwent a reliability analyses and preliminary validation with 115 women.
      A second sample of 126 women was used to conduct further validation and samples
      were pooled to conduct factor analysis and the final scale selection. RESULTS: A
      17-item self-concept scale emerged having three factors: stigma, vulnerability
      and mastery demonstrating evidence for an instrument with promising psychometric
      properties (total scale alpha=0.90). CONCLUSIONS: The scale has direct relevance
      for research in facilitating our understanding of the specific aspects of the
      self, which are vulnerable to BRCA1/2 testing and which play a role in clinical
      outcomes, to facilitate the development and specific testing of interventions and
      may be used as an outcome measure. Specific measurement tools for genetic
      populations will ultimately assist in the clinical management of these
      populations.

PMID- 19180530
TI  - A brief self-administered psychological intervention to improve well-being in
      patients with cancer: results from a feasibility study.
AB  - BACKGROUND: Patients with cancer have relatively high rates of anxiety and
      distress, adversely affecting their well-being and quality of life. Recent
      studies indicate that addressing these symptoms could result in better response
      to cancer treatment. Researchers have found that interventions that focus on
      increasing mental awareness and the frequency of positive experiences may have a
      greater impact on reducing psychological morbidity and increasing quality of life
      than interventions that target relief of psychological symptoms. AIM: To develop
      and test a brief, easy to use intervention that could improve well-being and
      quality of life in cancer patients. METHODS: We developed a simple well-being
      intervention that made few demands on patient time and required little training
      resource. Participants were randomly assigned to an intervention group or a
      deferred entry group. Measures of anxiety, depression, well-being and quality of
      life were administered at baseline and at follow-ups. RESULTS: Twenty-two women
      with metastatic breast cancer and 24 men with metastatic prostate cancer were
      recruited from oncology clinics. Thirteen women and 14 men completed the study.
      Both qualitative and quantitative data showed that the intervention was
      acceptable to users. There was statistically significant improvement in quality
      of life scores on WHOQOL-BREF post-intervention (p=0.046). Compliance with the
      intervention was good. CONCLUSIONS: This brief well-being intervention appears to
      be a promising technique for improving quality of life of cancer patients,
      without making undue demands on staff resources or patient time. If further
      studies confirm its effectiveness, it could prove to be a cost-effective
      intervention.

PMID- 19180531
TI  - Modeling spatial learning in rats based on Morris water maze experiments.
AB  - The Morris water maze, developed by Morris (J Neurosci Methods 1984: 11: 47-60),
      is a behavioral experiment designed to test the spatial memory. When repeating
      the experiment several times, the changes in time (latency) and distance (path)
      taken to reach the platform are indicators for the learning and memory abilities
      of the rat. In juvenile toxicity studies, it is of interest to test whether
      dosing juvenile rats with some compound of interest has an effect on its learning
      ability. The traditional analysis uses non-parametric tests to check for a
      possible dose-effect. However, due to the many tests performed, this approach
      lacks power. Here, an alternative method is proposed, accounting for the
      longitudinal design of the study, the right-censoring of observations when
      animals did not find the platform and the correlation between the time and
      distance taken to reach the platform.

PMID- 19180532
TI  - A 2-DE MALDI-TOF study to identify disease regulated serum proteins in lung
      cancer of c-myc transgenic mice.
AB  - We previously reported targeted overexpression of c-myc to alveolar epithelium to
      cause lung cancer. We now extended our studies to the serum proteome of tumor
      bearing mice. Proteins were extracted with a thiourea-containing lysis buffer and
      separated by 2-DE at pH 4-7 and 3-10 followed by MALDI-TOF/TOF analysis. Forty
      six proteins were identified in tumor bearing mice of which n = 9 were
      statistically significant. This included disease regulated expression of
      orosomucoid-8, alpha-2-macroglobulin, apolipoprotein-A1, apolipoprotein-C3,
      glutathione peroxidase-3, plasma retinol-binding protein, and transthyretin,
      while expression of apolipoprotein-E was decreased at late stages of disease.
      Moreover, serum amyloid P component was uniquely expressed at late stages of
      cancer. It is of considerable importance that most disease regulated proteins
      carried the E-Box sequence (CACGTG) in the promoter of the coding gene, therefore
      providing evidence for their regulation by c-myc. Notably, expression of alpha-2
      macroglobulin, transthyretin, alpha-1-antitrypsin, and properdin was in common in
      different lung tumor models, but regulation of orosomucoid-8, apolipoprotein-A1,
      apolipoprotein-C3, apolipoprotein-E, glutathione peroxidase-3, plasma retinol
      binding protein, and serum amyloid P component was unique when the serum
      proteomes of c-myc and c-raf tumor bearing mice were compared. Therefore,
      candidate biomarkers to differentiate between atypical adenomatous hyperplasias
      (AAH) and bronchiolo-alveolar carcinomas (BAC)/papillary adenocarcinomas (PLAC)
      can be proposed.

PMID- 19180533
TI  - Diophantine analysis complements electrospray-Q-TOF data for structure
      elucidation of transferrin glycoforms used for clinical diagnosis in human serum
      and cerebrospinal fluid.
AB  - The use of ESI-Q-TOF in combination with theoretical mapping of possible glycan
      variants by Diophantine mass analysis allows identification of transferrin (Tf)
      glycoforms in different biological fluids including human serum and cerebrospinal
      fluid (CSF). In order to restrict the structural variations, a chromatographic
      separation (HPLC) of the forms with different number of sialic acids is initially
      conducted. The individual fractions are purified, preconcentrated, and analyzed
      by ESI-Q-TOF. The results obtained experimentally are compared with those
      predicted by Diophantine calculations and the structures proposed. Each one of
      the found masses can be ascribed to a single Tf glycoform with a mass difference
      that ranged between -1 and -26 Da (average masses). Thus, the methodology can be
      used for structural characterization of Tf glycoforms relevant for clinical
      diagnosis without enzymatic digestion.

PMID- 19180534
TI  - Identification of novel Stat6 regulated proteins in IL-4-treated mouse
      lymphocytes.
AB  - Interleukin 4 (IL-4) has an indispensable role in the differentiation of naive T
      helper (Th) cells toward the Th2 phenotype and induction of B cells to produce
      the IgE class of Igs. By regulating these two cell types, IL-4 has a pre-eminent
      role in regulation of allergic inflammation. IL-4-mediated regulation of T and B
      cell functions is largely transmitted through signal transducer and activator of
      transcription 6 (Stat6). In this study, we have used metabolic labeling and 2-D
      electrophoresis to detect differences in the proteomes of IL-4 stimulated spleen
      mononuclear cells of Stat6-/- and wild type mice and MS/MS for protein
      identification. With this methodology, we identified 49 unique proteins from 21
      protein spots to be differentially expressed. Interestingly, in Stat6-/- CD4(+)
      cells the expression of isoform 2 of core binding factor b (CBFb2) was enhanced.
      CBFb is a non-DNA binding cofactor for the Runx family of transcription factors,
      which have been implicated in regulation of Th cell differentiation. We also
      found cellular nucleic acid protein (CNBP) to be downregulated in Stat6-/- cells.
      None of the proteins identified in this study have previously been reported to be
      regulated via Stat6. The results highlight the importance of exploiting
      proteomics tools to complement the studies on Stat6 target genes identified
      through transcriptional profiling.

PMID- 19180535
TI  - Proteomics of skeletal muscle aging.
AB  - Extended human longevity has resulted in increasing numbers of elderly persons in
      the general population. However, old age is also associated with a variety of
      serious physical disorders. Frailty among sedentary elderly patients is related
      to the impaired structure and function of contractile fibers. Biochemical
      research into cellular mechanisms that underlie sarcopenia promises to acquire
      the scientific basis of evidence to aid the development of new diagnostic and
      therapeutic strategies. The recent application of MS-based proteomic methodology
      has identified a large cohort of disease-specific markers of sarcopenia. This
      review critically examines the biomedical implications of the results obtained
      from the proteomic screening of both aged human muscle and established animal
      models of sarcopenia. Substantial alterations in proteins involved in key
      metabolic pathways, regulatory and contractile elements of the actomyosin
      apparatus, myofibrillar remodeling and the cellular stress response are
      discussed. A multi-factorial etiology appears to be the basis for a slower
      twitching aged fiber population, which exhibits a shift to more aerobic-oxidative
      metabolism. It is hoped that the detailed biomedical characterization of the
      newly identified biomarkers of sarcopenia will translate into better treatment
      options for reversing age-dependent muscle degeneration, which could improve the
      standard of living for a large portion of society.

PMID- 19180536
TI  - Multiplex expression cloning of blood-brain barrier membrane proteins.
AB  - The blood-brain barrier (BBB) is a vascular endothelial interface that separates
      the brain interior from the bloodstream. Membrane proteins resident at the BBB
      play important functional and regulatory roles. The current study describes the
      development and successful implementation of a multiplex expression cloning (MEC)
      method to allow facile identification of BBB membrane proteins. The overriding
      goal of the MEC approach was to mine a BBB cDNA library and selectively isolate
      membrane protein-encoding cDNAs. This selection process was achieved via
      fluorescence-activated cell sorting (FACS) of cDNA-expressing mammalian host
      cells for those cells that were immunolabeled with a BBB membrane protein
      specific polyclonal antiserum (BMSPA). After optimization of the host cell
      expression system, four selection rounds allowed the isolation of a panel of 15
      unique cDNAs that encoded BBB membrane proteins. The identified proteins display
      significant diversity in structure, function and in vivo expression levels. The
      MEC approach thus proved effective for conducting moderate throughput membrane
      proteome analyses of the BBB while limiting any biases caused by membrane protein
      insolubility or low in vivo expression levels that can complicate other proteomic
      approaches.

PMID- 19180537
TI  - Alteration in the glycan pattern of pilin in a nonmotile mutant of Synechocystis
      sp. PCC 6803.
AB  - Pilus-mediated motility is essential for the optimization of photosynthesis and
      environmental adaptation in the cyanobacterium Synechocystis sp. PCC 6803
      (Syn6803). To identify the genes required for pilus-mediated motility in Syn6803,
      we applied a forward genetic approach using a Tn5 mutant library and reverse
      genetics using interposon mutagenesis. One of the identified genes, sll0899,
      bears sequence similarity to acyltransferases and nucleotidyltransferases. The
      sll0899 gene product is not involved in the transcription or translation of
      pilA1, which encodes pilin, the major component of pili. Instead, the
      sll0899::Cm(r) mutant produced pilins with increased molecular mass, suggesting
      the existence of different PTMs. Using MS, we found that the wild-type (WT) and
      mutant pilins were glycosylated between amino acids 67 and 75. Analyses by
      quantitative MS and high-pH anion exchange chromatography (HPAEC) revealed that
      the glycan in WT pilin is composed of xylose and fucose, whereas an additional
      sugar, rhamnose, was found in the glycan of sll0899::Cm(r). Our findings suggest
      that an alteration in the O-linked glycan of pilin is responsible for the loss of
      pilus-mediated motility in sll0899::Cm(r).

PMID- 19180538
TI  - Overflow of a hyper-produced secretory protein from the Bacillus Sec pathway into
      the Tat pathway for protein secretion as revealed by proteogenomics.
AB  - Bacteria secrete numerous proteins into their environment for growth and survival
      under complex and ever-changing conditions. The highly different characteristics
      of secreted proteins pose major challenges to the cellular protein export
      machinery and, accordingly, different pathways have evolved. While the main
      secretion (Sec) pathway transports proteins in an unfolded state, the twin
      arginine translocation (Tat) pathway transports folded proteins. To date, these
      pathways were believed to act in strictly independent ways. Here, we have
      employed proteogenomics to investigate the secretion mechanism of the esterase
      LipA of Bacillus subtilis, using a serendipitously obtained hyper-producing
      strain. While LipA is secreted Sec-dependently under standard conditions, hyper
      produced LipA is secreted predominantly Tat-dependently via an unprecedented
      overflow mechanism. Two previously identified B. subtilis Tat substrates, PhoD
      and YwbN, require each a distinct Tat translocase for secretion. In contrast,
      hyper-produced LipA is transported by both Tat translocases of B. subtilis,
      showing that they have distinct but overlapping specificities. The identified
      overflow secretion mechanism for LipA focuses interest on the possibility that
      secretion pathway choice can be determined by environmental and intracellular
      conditions. This may provide an explanation for the previous observation that
      many Sec-dependently transported proteins have potential twin-arginine signal
      peptides for export via the Tat pathway.

PMID- 19180539
TI  - Genome-wide analysis and proteomic studies reveal APE1/Ref-1 multifunctional role
      in mammalian cells.
AB  - Apurinic apyrimidinic endonuclease/redox effector factor 1 (APE1/Ref-1) protects
      cells from oxidative stress by acting as a central enzyme in base excision repair
      pathways of DNA lesions and through its independent activity as a redox
      transcriptional co-activator. Dysregulation of this protein has been associated
      with cancer development. At present, contrasting data have been published
      regarding the biological relevance of the two functions as well as the molecular
      mechanisms involved. Here, we combined both mRNA expression profiling and
      proteomic analysis to determine the molecular changes associated with APE1 loss
      of-expression induced by siRNA technology. This approach identified a role of
      APE1 in cell growth, apoptosis, intracellular redox state, mitochondrial
      function, and cytoskeletal structure. Overall, our data show that APE1 acts as a
      hub in coordinating different and vital functions in mammalian cells,
      highlighting the molecular determinants of the multifunctional nature of APE1
      protein.

PMID- 19180540
TI  - Infrared-assisted proteolysis using trypsin-immobilized silica microspheres for
      peptide mapping.
AB  - A novel proteolysis approach was developed by using infrared (IR) radiation and
      trypsin-immobilized silica microspheres. Protein solutions containing trypsin
      immobilized microspheres in sealed transparent Eppendorf tubes were allowed to
      digest under an IR lamp at 37 degrees C. The feasibility and performance of the
      present proteolysis approach were demonstrated by the digestion of BSA and
      cytochrome c (Cyt-c) and the digestion time was significantly reduced to 5 min.
      The obtained digests were identified by MALDI-TOF-MS with the sequence coverages
      of 54% (BSA) and 83% (Cyt-c) that were better than those obtained by conventional
      in-solution tryptic digestion. The suitability of the new digestion approach to
      complex proteins was demonstrated by digesting human serum. The present
      proteolysis strategy is simple and efficient and will find a wide range of
      application in protein identification.

PMID- 19180541
TI  - Using mass spectrometry to identify ubiquitin and ubiquitin-like protein
      conjugation sites.
AB  - Ubiquitin (Ub) and the ubiquitin-like proteins (Ubls) are polypeptides that are
      covalently conjugated to proteins and other biomolecules to modulate their
      turnover rate, localization, and/or function. The full range of Ubl functions is
      only beginning to be understood, and the wide variety of Ubl conjugates is only
      beginning to be identified. Moreover, how Ubl conjugation is regulated, and how
      Ubl conjugate populations change, e.g., throughout the cell cycle, in response to
      hormones, nutrients, or stress, or in various disease states, remains largely
      enigmatic. MS represents a powerful tool for the characterization of PTMs.
      However, standard sample preparation and data search methods are not amenable to
      the identification of many types of Ubl conjugates. Here, we describe the
      challenges of identifying Ub/Ubl conjugates, and propose an improved workflow for
      identification of Ub/Ubl conjugation sites. Considering the importance of Ubls in
      normal cellular physiology, and their roles in disease etiology and progression,
      it will be critical to develop improved high-throughput MS methods capable of
      efficiently identifying proteins and other biomolecules modified by these very
      interesting and important PTMs.

PMID- 19180542
TI  - Comparison of aromatic and alkyl micelles for the electrokinetic determination of
      phthalates in virgin olive oil.
AB  - Two electrokinetic methods for the separation of phthalates are proposed. One
      uses 25 mM sodium borate and 50 mM sodium taurodeoxycholate adjusted to pH 2.8,
      and the other uses 15 mM ammonium tetraborate, 100 mM SDS, 0.25% w:v
      hydroxypropylmethyl cellulose (HPMC) and 5% v:v methanol (MeoH) adjusted to pH 9.
      The BGE containing SDS micelles as the pseudo-stationary phase provided better
      analytical figures of merit, particularly as regards LOD (0.4-1.4 mg/L) and
      precision (1.1-6.5%). Adding MeoH and HPMC to the BGE proved essential in order
      to obtain narrow and symmetric peaks. The proposed method was successfully used
      to determine phthalates in virgin olive oil. Recoveries from spiked samples
      ranged from 96 to 106%. The precision obtained in the analysis of real samples,
      as RSD, was better than 6.8%.

PMID- 19180543
TI  - Rapid quantitative analysis of letrozole, fluoxetine and their metabolites in
      biological and environmental samples by MEKC.
AB  - A micellar electrokinetic chromatographic method has been developed to analyze
      biological (human serum, saliva and urine) and environmental samples (three
      different water samples) for letrozole (LE), fluoxetine and their main
      metabolites. For this purpose a 20 mM borate buffer (pH 9.5) containing 20 mM SDS
      and 12% v:v 2-propanol was used as the background electrolyte. The samples were
      hydrodynamically injected for 6 s, separated in a fused-silica capillary at 25 kV
      and 50 degrees C and detected at 230 nm. Under these conditions, the migration
      times for all the studied compounds ranged from 3.0 up to 8.0 min. Linearity
      ranges were determined as 125-1500 ng/mL, whereas detection limits were from 37
      to 120 ng/mL in biological samples and a value of 6 ng/mL in water samples.
      According to the validation study, the developed method was proved to be
      accurate, precise, sensitive, specific, rugged and robust. This method was
      applied to the analysis of different biological fluids at clinical levels,
      including two urine samples from patients undergoing treatment with LE or
      fluoxetine, and also to environmental samples at potentially polluting level.
      Prior to the determination, the samples were purified and pre-concentrated by
      means of an extraction-preconcentration step with a C18 cartridge and by eluting
      the compounds with methanol.

PMID- 19180544
TI  - Analysis of aliphatic amines using head-column field-enhanced sample stacking in
      MEKC with LIF detection.
AB  - This paper describes the use of head-column field-enhanced sample stacking for on
      line sample concentration in MEKC; the method has been applied to the
      determination of C1-C9 aliphatic amines after their pre-capillary derivatization
      with 3-(4-carboxybenzoyl) quinoline-2-carboxaldehyde (CBQCA). The optimum
      derivatization, on-line concentration and separation conditions for these
      aliphatic amines were investigated in detail. The optimized molar ratio of CBQCA
      to amines was found to be 120:1, and 50 mmol/L borate buffer (pH 9.5) was used
      for derivatization in order to achieve high efficiency. Nine imidazole aliphatic
      amines were baseline separated within 12 min by using 50 mmol/L of sodium borate
      (pH 9.5) and 15 mmol/L of SDS as running buffer. Under the optimum conditions,
      the detection limits of these nine aliphatic amines ranged from 1.2 to 3.8
      pmol/L. S/N=3, which was about 49-173-fold lower than those of conventional
      sample injections. After validation, the developed method was applied to the
      determination of C1-C9 aliphatic amines in river water with the average
      recoveries of 86.7-105%.

PMID- 19180545
TI  - Field-amplified sample injection for the determination of albumin and transferrin
      in human urines by MEKC.
AB  - An MEKC method combining field-amplified sample injection (FASI) has been
      developed for the analysis of albumin (Alb) and transferrin (TRF) in human
      urines. Various parameters affecting FASI preconcentration were optimized
      systematically. Under the optimum conditions, using electrokinetic sample
      injection for 90 s, the sensitivity was improved 77.6- and 45.3-fold for TRF and
      Alb, respectively, without loss of separation efficiency when compared with
      hydrodynamical sample injection for 5 s (0.5 psi). The detection limits of TRF
      and Alb were found to be 0.31 and 0.14 mg/L, respectively. The proposed method
      has been successfully applied to the determination of TRF and Alb in desalted
      urines from patients with kidney diseases, and the recoveries of TRF and Alb were
      91.1-101.7%.

PMID- 19180546
TI  - Preparation and characterization of temperature-responsive capillary
      electrochromatographic column using poly(N-isopropylacrylamide).
AB  - Poly(N-isopropylacrylamide) is a temperature-responsive polymer, which is
      hydrophilic at low temperature but hydrophobic at high temperature. Using this
      characteristic, the polymer was bonded to the inner surface of fused-silica
      capillary to prepare a temperature-responsive column to study the separation
      behavior in electrochromatography.

PMID- 19180549
TI  - Crosslinking metal nanoparticles into the polymer backbone of hydrogels enables
      preparation of soft, magnetic field-driven actuators with muscle-like
      flexibility.
AB  - The combination of force and flexibility is at the core of biomechanics and
      enables virtually all body movements in living organisms. In sharp contrast,
      presently used machines are based on rigid, linear (cylinders) or circular
      (rotator in an electrical engine) geometries. As a potential bioinspired
      alternative, magnetic elastomers can be realized through dispersion of micro- or
      nanoparticles in polymer matrices and have attracted significant interest as soft
      actuators in artificial organs, implants, and devices for controlled drug
      delivery. At present, magnetic particle loss and limited actuator strength have
      restricted the use of such materials to niche applications. We describe the
      direct incorporation of metal nanoparticles into the backbone of a hydrogel and
      application as an ultra-flexible, yet strong magnetic actuator. Covalent bonding
      of the particles prevents metal loss or leaching. Since metals have a far higher
      saturation magnetization and higher density than oxides, the resulting increased
      force/volume ratio afforded significantly stronger magnetic actuators with high
      mechanical stability, elasticity, and shape memory effect.

PMID- 19180552
TI  - Beta-amyloid cortical deposits are accompanied by the loss of serotonergic
      neurons in the dog.
AB  - Dogs may naturally suffer an age-related cognitive impairment that has aroused a
      great deal of interest, even beyond the field of the veterinary clinic. This
      canine senile dementia reproduces several key aspects of Alzheimer's disease
      (AD), including the presence of beta-amyloid (A beta) deposits in the cerebral
      cortex, neurodegeneration, and learning and memory impairments. In the present
      study, we have used unbiased stereological procedures to estimate the number of
      the dorsal and median raphe nuclei (DRN and MRN, respectively) serotonergic
      neurons immunolabeled with an anti-tryptophan hydroxylase (TrH) monoclonal
      antibody in young and aged dogs without A beta cortical deposits and in aged dogs
      with A beta cortical deposits. The estimated total number of TrH-labeled neurons
      (mean +/- SD) was 94,790 +/- 26,341 for the DRN and 40,404 +/- 8,692 for the MRN.
      The statistical analyses revealed that aged dogs with A beta cortical pathology
      had 33% fewer serotonergic neurons in the DRN and MRN than aged dogs without A
      beta cortical deposits (108,043 +/- 18,800 vs. 162,242 +/- 39,942, respectively;
      P = 0.01). In contrast, no significant variations were found between young and
      aged dogs without A beta cortical deposits. These results suggest that
      degeneration of the serotonergic neurons could be involved in the cognitive
      damage that accompanies A beta cortical pathology in the dog and reinforce the
      use of the canine model for exploring the potential mechanisms linking the
      cortical A beta pathology and serotonergic neurodegeneration that occurs during
      the course of AD.

PMID- 19180555
TI  - Visual acuity in the cathemeral strepsirrhine Eulemur macaco flavifrons.
AB  - Studies of visual acuity in primates have shown that diurnal haplorhines have
      higher acuity (30-75 cycles per degree (c/deg)) than most other mammals. However,
      relatively little is known about visual acuity in non-haplorhine primates, and
      published estimates are only available for four strepsirrhine genera (Microcebus,
      Otolemur, Galago, and Lemur). We present here the first measurements of visual
      acuity in a cathemeral strepsirrhine species, the blue-eyed black lemur (Eulemur
      macaco flavifrons). Acuity in two subjects, a 3-year-old male and a 16-year-old
      female, was assessed behaviorally using a two-alternative forced choice
      discrimination task. Visual stimuli consisted of high contrast square wave
      gratings of seven spatial frequencies. Acuity threshold was determined using a
      70% correct response criterion. Results indicate a maximum visual acuity of 5.1
      c/deg for the female (1718 trials) and 3.8 c/deg for the male (846 trials). These
      values for E. macaco are slightly lower than those reported for diurnal Lemur
      catta, and are generally comparable to those reported for nocturnal Microcebus
      murinus and Otolemur crassicaudatus. To examine ecological sources of variation
      in primate visual acuity, we also calculated maximum theoretical acuity for
      Cheirogaleus medius (2.8 c/deg) and Tarsius syrichta (8.9 c/deg) using published
      data on retinal ganglion cell density and eye morphology. These data suggest that
      visual acuity in primates may be influenced by activity pattern, diet, and
      phylogenetic history. In particular, the relatively high acuity of T. syrichta
      and Galago senegalensis suggests that visual predation may be an important
      selective factor favoring high visual acuity in primates.

PMID- 19180556
TI  - Blind identification of evoked human brain activity with independent component
      analysis of optical data.
AB  - Diffuse optical tomography (DOT) methods observe hemodynamics in the brain by
      measuring light transmission through the scalp, skull, and brain. Thus,
      separating signals due to heart pulsations, breathing movements, and systemic
      blood flow fluctuations from the desired brain functional responses is critical
      to the fidelity of the derived maps. Herein, we applied independent component
      analysis (ICA) to temporal signals obtained from a high-density DOT system used
      for functional mapping of the visual cortex. DOT measurements were taken over the
      occipital cortex of human adult subjects while they viewed stimuli designed to
      activate two spatially distinct areas of the visual cortex. ICA was able to
      extract clean functional hemodynamic signals and separate brain activity sources
      from hemodynamic fluctuations related to heart and breathing without knowledge of
      the stimulus paradigm. Furthermore, independent components were found defining
      distinct functional responses to each stimulus type. Images generated from single
      ICA components were comparable, with regard to spatial extent and resolution, to
      images from block averaging (with knowledge of the block stimulus paradigm). Both
      images and estimated time-series signals demonstrated that ICA was superior to
      principal component analysis in extracting the true event-evoked response
      signals. Our results suggest that ICA can extract the time courses and the
      corresponding spatial extent of functional responses in DOT imaging.

PMID- 19180557
TI  - Cardiorespiratory effects on default-mode network activity as measured with fMRI.
AB  - The default-mode network (DMN) consists of areas showing more activation during
      rest than during a task. Several authors propose some form of cognitive
      processing to underlie BOLD signal changes in the DMN as activity within the
      network is modulated by the level of effort required by the task and is
      positively correlated with self-referential processing. Alternatively, BOLD
      signal changes within the DMN may be caused by cardiorespiratory processes (CR)
      affecting BOLD signal measurements independent of neuronal activity. The goal of
      this study is to investigate whether BOLD signal changes within the DMN can be
      explained by CR effects. To this aim, brain activity, heartbeat, and respiration
      are measured during resting-state and while subjects perform a cognitive task
      with a high- and low-demand condition. To correct for CR effects we used
      RETROICOR (Glover et al., [2000]: Magn Reson Med 44:162-167) in combination with
      additive linear modeling of changes due to respiration volume, heart rate and
      heart rate variability. CR effects were present within the frequency-range of the
      DMN and were located in areas of the DMN, but equally so in other areas. After
      removal of CR effects, deactivation and resting-state connectivity between the
      areas of the DMN remained significant. In addition, DMN deactivation was still
      modulated by task demand. The same CR correction method did remove activation in
      task-related areas. We take these results to indicate that the BOLD signal within
      the DMN cannot be explained by CR effects alone and is possibly related to some
      form of cognitive neuronal processing.

PMID- 19180558
TI  - Activation of the caudal anterior cingulate cortex due to task-related
      interference in an auditory Stroop paradigm.
AB  - Successful information processing requires the focusing of attention on a certain
      stimulus property and the simultaneous suppression of irrelevant information. The
      Stroop task is a useful paradigm to study such attentional top-down control in
      the presence of interference. Here, we investigated the neural correlates of an
      auditory Stroop task using fMRI. Subjects focused either on tone pitch
      (relatively high or low; phonetic task) or on the meaning of a spoken word
      (high/low/good; semantic task), while ignoring the other stimulus feature. We
      differentiated between task-related (phonetic incongruent vs. semantic
      incongruent) and sensory-level interference (phonetic incongruent vs. phonetic
      congruent). Task-related interference activated similar regions as in visual
      Stroop tasks, including the anterior cingulate cortex (ACC) and the
      presupplementary motor-area (pre-SMA). More specifically, we observed that the
      very caudal/posterior part of the ACC was activated and not the dorsal/anterior
      region. Because identical stimuli but different task demands are compared in this
      contrast, it reflects conflict at a relatively high processing level. A more
      conventional contrast between incongruent and congruent phonetic trials was
      associated with a different cluster in the pre-SMA/ACC which was observed in a
      large number of previous studies. Finally, functional connectivity analysis
      revealed that activity within the regions activated in the phonetic incongruent
      vs. semantic incongruent contrast was more strongly interrelated during
      semantically vs. phonetically incongruent trials. Taken together, we found
      (besides activation of regions well-known from visual Stroop tasks) activation of
      the very caudal and posterior part of the ACC due to task-related interference in
      an auditory Stroop task.

PMID- 19180559
TI  - Upper-extremity musculoskeletal symptoms and physical health related quality of
      life among women employed in poultry processing and other low-wage jobs in
      northeastern North Carolina.
AB  - BACKGROUND: The purpose of this study was to evaluate the association between
      upper-extremity musculoskeletal symptoms (MS) and diminished physical health
      related quality of life (PHRQoL) in a population of women, mostly African
      American working in poultry processing and other low-wage jobs in rural
      northeastern North Carolina. METHODS: A cross-sectional analysis was performed on
      baseline data of self-reported PHRQoL and musculoskeletal symptoms for 291
      poultry processing workers and 299 community comparison women. Logarithmic
      binomial regression was performed to assess the relationship between moderate to
      severe MS on low PHRQoL. RESULTS: Prevalence of poor PHRQoL was 35.5% among
      poultry processing workers, and 14.7% among community comparison group. Moderate
      to severe upper-extremity musculoskeletal symptoms were present in 34.4% of the
      poultry workers and 10.7% of the comparison group. After adjusting for age and
      other chronic conditions, moderate to severe musculoskeletal symptoms were
      associated with low PHRQoL in both groups. Although the observed effect was
      stronger among the comparison group (adjusted prevalence ratios (95% confidence
      interval): poultry workers = 1.89 (1.36, 2.64), community comparison = 4.26
      (2.51, 7.24), the population attributable risk percent was similar (poultry
      workers = 28.9, community comparison = 31.3%)) due to the higher prevalence of
      moderate to severe symptoms in the poultry workers. CONCLUSIONS: Significant
      upper-extremity musculoskeletal symptoms were associated with poor PHRQoL among
      both groups of women employed in low-wage jobs. Nationwide, poultry work is over
      represented by minorities and immigrants. Though challenging, we need to search
      for ways to improve the conditions of these women as a matter of social justice.

PMID- 19180562
TI  - Apoptosis in CADASIL: an in vitro study of lymphocytes and fibroblasts from a
      cohort of Italian patients.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is a hereditary disease affecting vascular smooth
      muscle cells of nearly all tissues. Clinical manifestations mainly concern the
      central nervous system with repeated TIA/stroke, migraine, psychiatric
      disturbances, and cognitive decline. Minor findings have been reported in muscle,
      nerve, and skin. CADASIL is due to NOTCH3 gene mutations. This gene has been
      identified as an up-regulator of c-FLIP, an inhibitor of Fas-ligand-induced
      apoptosis. The aim of this study was to assess the involvement of oxidative
      stress-induced apoptosis in cells from 16 Italian CADASIL patients. Peripheral
      blood lymphocytes (PBLs) and fibroblasts from CADASIL patients were exposed to 2
      deoxy-D-ribose (dRib), which induces apoptosis by oxidative stress. Apoptosis was
      analyzed by flow cytometry, agarose gel electrophoresis and fluorescence
      microscopy for caspase-3 activation, phosphatidylserine exposure and
      mitochondrial membrane depolarization. PBLs and fibroblasts from CADASIL patients
      showed a significantly higher response to dRib-induced apoptosis than those of
      controls. PBLs from CADASIL patients also showed a significantly higher
      percentage of apoptotic cells than PBLs from controls, even when cultured without
      dRib. The greater susceptibility of PBLs and fibroblasts from CADASIL patients to
      dRib-induced apoptosis suggests that NOTCH3 mutations are an important apoptotic
      trigger. Since PBLs from patients showed higher levels of apoptosis even in the
      absence of an apoptotic stimulus, cells from CADASIL patients appear to be
      physiologically prone to apoptotic cell death.

PMID- 19180561
TI  - Transforming growth factor-beta 1 (TGF-beta1) induces angiogenesis through
      vascular endothelial growth factor (VEGF)-mediated apoptosis.
AB  - VEGF and TGF-beta1 induce angiogenesis but have opposing effects on endothelial
      cells. VEGF protects endothelial cells from apoptosis; TGF-beta1 induces
      apoptosis. We have previously shown that VEGF/VEGF receptor-2 (VEGFR2) signaling
      mediates TGF-beta1 induction of apoptosis. This finding raised an important
      question: Does this mechanism stimulate or inhibit angiogenesis? Here we report
      that VEGF-mediated apoptosis is required for TGF-beta1 induction of angiogenesis.
      In vitro the apoptotic effect of TGF-beta1 on endothelial cells is rapid and
      followed by a long period in which the cells are refractory to apoptosis
      induction by TGF-beta1. Inhibition of VEGF/VEGFR2 signaling abrogates formation
      of cord-like structures by TGF-beta1 with an effect comparable to that of z-VAD,
      an apoptosis inhibitor. Similarly, genetic deficiency of VEGF abolishes TGF-beta1
      upregulation of endothelial cell differentiation and formation of vascular
      structures in embryoid bodies. In vivo TGF-beta1 induces endothelial cell
      apoptosis as rapidly as in vitro. Inhibition of VEGF blocks TGF-beta1 induction
      of both apoptosis and angiogenesis, an effect similar to that of z-VAD. Thus, TGF
      beta1 induction of angiogenesis requires a rapid and transient apoptotic effect
      mediated by VEGF/VEGFR2. This novel, unexpected role of VEGF and VEGFR2 indicates
      VEGF-mediated apoptosis as a potential target to control angiogenesis.

PMID- 19180563
TI  - ROS-mediated p38alpha MAPK activation and ERK inactivation responsible for
      upregulation of Fas and FasL and autocrine Fas-mediated cell death in Taiwan
      cobra phospholipase A(2)-treated U937 cells.
AB  - The aim of the present study is to explore the signaling pathway associated with
      Naja naja atra phospholipase A(2) (PLA(2))-induced apoptotic death of human
      leukemia U937 cells. Degradation of procaspases, production of tBid, loss of
      mitochondrial membrane potential, and cytochrome c release were observed in
      PLA(2)-treated cells. PLA(2) treatment increased Fas and FasL protein expression,
      and upregulated transcription of Fas and FasL mRNA. Upon exposure to PLA(2), ROS
      generation, p38 MAPK activation, and ERK inactivation were found in U937 cells.
      Abolition of PLA(2)-induced ROS generation abrogated p38 MAPK activation and
      upregulation of Fas and FasL expression, but restored ERK activation and
      viability of PLA(2)-treated cells. Block of p38 MAPK by SB202190 abolished PLA(2)
      induced Fas/FasL upregulation and ERK inactivation, but not ROS generation.
      Activated ERK suppressed p38 MAPK activation and Fas/FasL protein expression.
      Selective inactivation or overexpression of p38alpha MAPK proved that
      upregulation of Fas/FasL and ERK inactivation were related to p38alpha MAPK
      activation. Deprivation of catalytic activity with PLA(2) blocked completely
      PLA(2)-induced Fas/FasL upregulation. Downregulation of FADD abolished PLA(2)
      induced procaspase-8 degradation and rescued viability of PLA(2)-treated cells.
      Taken together, our results indicate that Fas/FasL upregulation in PLA(2)-treated
      U937 cells is elicited by ROS-mediated p38alpha MAPK activation and ERK
      inactivation, and suggest that autocrine Fas/FasL apoptotic mechanism is involved
      in PLA(2)-induced cell death. J. Cell. Physiol. 219: 642-651, 2009. (c) 2009
      Wiley-Liss, Inc.

PMID- 19180565
TI  - Heritability of neurocognitive traits in familial schizophrenia.
AB  - Neurocognitive deficits are considered promising endophenotypes for gene
      discovery in schizophrenia. Understanding the heritability and genetic inter
      relationships of neurocognitive traits could support their use as alternatives to
      diagnosis. Participants were 85 adults from 17 multiplex Canadian families with
      familial schizophrenia linked to 1q23 who had neurocognitive testing results
      available. Heritability of 13 standard measures assessing motor skills,
      processing speed, verbal, and visuospatial memory, attention/working memory,
      executive functioning, and IQ was estimated using variance component models and
      SOLAR software. We then investigated bivariate relationships between those
      variables found to be heritable. IQ showed the highest heritability (h(2) = 0.64
      0.74) and seven other neurocognitive measures, reflecting immediate and delayed
      verbal memory, attention/working memory, delayed visual memory, processing speed
      and motor skills, showed significant heritability (h(2) = 0.31-0.62) under one or
      more of the models assessed. A schizophrenia diagnostic covariate was significant
      (P < 0.0001) for all heritable variables. Bivariate analyses suggested that
      memory-IQ and visuomotor-processing speed formed two groups of heritable traits.
      The results provide further evidence of the heritability of selected
      neurocognitive measures, and their relationship to schizophrenia and underlying
      genetic architecture. Composite measures of memory or processing speed may be
      heritable phenotypes useful for studies of neurocognition.

PMID- 19180564
TI  - Genetic linkage findings for DSM-IV nicotine withdrawal in two populations.
AB  - Nicotine withdrawal (NW) is both an important contributor to difficulty quitting
      cigarettes and because of mood-related withdrawal symptoms a problem of
      particular relevance to psychiatry. Twin-studies suggest that genetic factors
      influence NW (heritability = 45%). Only one previous linkage study has published
      findings on NW [Swan et al. (2006); Am J Med Genet Part B 141B:354-360; LOD =
      2.7; Chr. 6 at 159 cM]. As part of an international consortium, genome-wide scans
      (using over 360 autosomal microsatellite markers) and telephone diagnostic
      interviews were conducted on 289 Australian (AUS) and 161 Finnish (FIN, combined
      (COMB) N = 450 families) families ascertained from twin registries through index
      cases with a lifetime history of cigarette smoking. The statistical approach used
      an affected-sib-pair design (at least two adult full siblings reported a history
      of DSM-IV NW) and conducted the linkage analyses using MERLIN. Linkage signals
      with LOD scores >1.5 were found on two chromosomes: 6 (FIN: LOD = 1.93 at 75 cM)
      and 11 at two different locations (FIN: LOD = 3.55 at 17 cM, and AUS: LOD = 1.68
      with a COMB: LOD = 2.30 at 123 cM). The multipoint LOD score of 3.55 on
      chromosome 11p15 in FIN met genomewide significance (P = 0.013 with 1,000
      simulations). At least four strong candidate genes lie within or near this peak
      on chromosome 11: DRD4, TPH, TH, and CHRNA10. Other studies have reported that
      chromosome 11 may harbor genes associated with various aspects of smoking
      behavior. This study adds to that literature by highlighting evidence for NW.

PMID- 19180568
TI  - Understanding the causes and prevention of neural tube defects: Insights from the
      splotch mouse model.
AB  - Splotch mutant mice develop neural tube defects (NTDs), comprising exencephaly
      and/or spina bifida, as well as neural crest-related defects and abnormalities of
      limb musculature. Defects in splotch mice result from mutations in Pax3, and some
      human NTDs may also result from mutations in the human PAX3 gene. Pax3 encodes a
      transcription factor whose function may influence expression of multiple
      downstream genes associated with a variety of cellular properties (including
      apoptosis, adhesion, proliferation, and differentiation), that could be important
      for neural tube closure. The frequency of NTDs varies between mutant alleles and
      is also influenced by genetic background and environmental factors. Notably,
      splotch provides a model for folic acid-preventable NTDs, and conversely, dietary
      folate deficiency exacerbates NTDs. Understanding the molecular and cellular
      basis of splotch NTDs, as well as the mechanisms by which the frequency of
      defects is influenced by genetic and environmental factors (such as sub-optimal
      folate status), may provide insight into the causation of these severe congenital
      malformations in humans.

PMID- 19180567
TI  - Insights into metabolic mechanisms underlying folate-responsive neural tube
      defects: a minireview.
AB  - Neural tube defects (NTDs), including anencephaly and spina bifida, arise from
      the failure of neurulation during early embryonic development. Neural tube
      defects are common birth defects with a heterogenous and multifactorial etiology
      with interacting genetic and environmental risk factors. Although the mechanisms
      resulting in failure of neural tube closure are unknown, up to 70% of NTDs can be
      prevented by maternal folic acid supplementation. However, the metabolic
      mechanisms underlying the association between folic acid and NTD pathogenesis
      have not been identified. This review summarizes our current understanding of the
      mechanisms by which impairments in folate metabolism might ultimately lead to
      failure of neural tube closure, with an emphasis on untangling the relative
      contributions of nutritional deficiency and genetic risk factors to NTD
      pathogenesis.

PMID- 19180570
TI  - Cyr61 is up-regulated in prostate cancer and associated with the p53 gene status.
AB  - Cysteine-rich 61 (Cyr61) is a member of the CCN protein family that has been
      implicated in diverse biological processes such as cell adhesion, proliferation,
      angiogenesis, and tumorigenesis. Altered expression of Cyr61 is found to be
      associated with human cancers. Here we show that Cyr61 was up-regulated in
      prostate cancer cell lines and tumor tissues. A significant correlation of Cyr61
      expression was found between benign prostatic hyperplasia and prostate cancer (P
      = 0.002). However, there was no significant correlation between levels of PSA and
      Cyr61 expression (P = 0.2). Cyr61 may represent an independent prostate cancer
      biomarker and potentially a useful therapeutic target for prostate cancer
      treatment. In addition, our analysis based on published data and data present in
      this report indicted that levels of Cyr61 expression associated with the status
      of the tumor suppressor gene p53 in 32 cancer cell lines analyzed, high levels of
      Cyr61 expression were found in cell lines with mutant or null p53 gene, whereas
      lower expression levels of Cyr61 in the cell lines with wild-type p53. We further
      show that over-expression of dominant negative p53 or down-expression of
      endogenous wild-type p53 resulted in up-regulation of Cyr61 expression,
      suggesting a functional link between Cyr61 and p53 in cancers.

PMID- 19180569
TI  - Prostatic soy isoflavone concentrations exceed serum levels after dietary
      supplementation.
AB  - BACKGROUND: The effects of soy isoflavones on prostate cancer may be
      concentration-dependent. The impact of soy supplementation on isoflavone
      concentrations in prostate tissues and serum remain unclear. OBJECTIVE: To assess
      and compare concentrations of soy isoflavones in prostate tissue and serum among
      19 men with prostate cancer who had elected to undergo radical prostatectomy.
      METHODS: Participants were randomized to receive either daily soy supplements (82
      mg/day aglycone equivalents) or placebos for 2 weeks (14 days) prior to surgery.
      Serum samples were obtained at the time of the surgery. Isoflavone concentrations
      were measured by HPLC/ESI-MS-MS. RESULTS: The median (25th, 75th percentile)
      total isoflavone concentration in the isoflavone-supplemented group was 2.3
      micromol/L (1.2, 6.9) in the prostate tissue and 0.7 micromol/L (0.2, 1.2) in the
      serum. Total isoflavone concentrations in this group were an average of
      approximately 6-fold higher in prostate tissue compared to serum; the tissue
      versus serum ratio was significantly lower for genistein than daidzein, 4-fold
      versus 10-fold, P = 0.003. Tissue and serum levels of isoflavones among the
      placebo group were negligible with a few exceptions. CONCLUSIONS: The findings
      from the present study suggest that prostate tissue may have the ability to
      concentrate dietary soy isoflavones to potentially anti-carcinogenic levels.

PMID- 19180571
TI  - JAK pathway induction of c-Myc critical to IL-5 stimulation of cell proliferation
      and inhibition of apoptosis.
AB  - Interleukin-5 (IL-5) induction of c-Myc expression is associated with IL-5
      inhibition of apoptosis in hematopoietic cells. In this study, TFalpha1 and
      TFalpha8 cells with stable overexpression of IL-5 receptor alpha (IL-5Ralpha)
      subunit in TF-1 cells, a human hematopoietic progenitor cell line which expressed
      low levels of IL-5Ralpha, were used to explored how IL-5 up-regulate c-Myc and
      the role of c-Myc in IL-5 signaling. First, we demonstrate that IL-5 induced c
      Myc RNA and protein expressions, as well as activated Janus kinases (JAK1 and
      JAK2) and signal transducer and activator of transcription-5b (STAT5b). JAK
      inhibitor AG490 and c-Myc inhibitor 10058-F4, both, reduced IL-5-mediated cell
      proliferation in a dose- and time-dependent manner. Both, AG490 and 10058-F4,
      also reduced IL-5-mediated anti-apoptotic activity. Furthermore, AG490 inhibited
      IL-5-mediated c-Myc induction and promoter activity. We further examined the role
      of JAK1 and JAK2 in the induction of c-Myc expression using the CDJAK fusion
      proteins, which consisted of a CD16 extracellular domain, a CD7 transmembrane
      domain, and either JAK1 (CDJAK1) or JAK2 (CDJAK2) as intracellular domains.
      Simultaneous activation of JAK1 and JAK2 by anti-CD16 antibody crosslinking of
      CDJAK1 and CDJAK2 could induced c-Myc expression and promoter activity; AG490
      inhibited CDJAK1 and CDJAK2-mediated effects. These results suggest that IL-5
      induces cell proliferation and anti-apoptosis through the JAK/c-Myc pathway, and
      that JAK1 and JAK2 activation participate in IL-5-induced up-regulation of c-Myc.

PMID- 19180572
TI  - Characterization of PEDF: a multi-functional serpin family protein.
AB  - Pigment epithelium-derived factor (PEDF) is a 50 kDa secreted glycoprotein that
      belongs to the non-inhibitory serpin family group. PEDF has been described as a
      natural angiogenesis inhibitor with neurotrophic and immune-modulation
      properties; it balances angiogenesis in the eye and blocks tumor progression. The
      mechanisms underlying most of these events are not completely clear; however, it
      appears that PEDF acts via multiple high affinity ligands and cell receptors. In
      this review article, we will summarize the current knowledge on the biochemical
      properties of PEDF and its receptors, the multimodal activities of PEDF and
      finally address the therapeutic potential of PEDF in treating angiogenesis-,
      neurodegeneration- and inflammation-related diseases.

PMID- 19180573
TI  - Prenatal diagnosis of Nager syndrome in a monochorionic-diamniotic twin
      pregnancy.

PMID- 19180574
TI  - Parathyroid hormone synergizes with non-cyclic AMP pathways to activate the
      cyclic AMP response element.
AB  - Parathyroid hormone (PTH) activates multiple signaling pathways following binding
      to the PTH1 receptor in osteoblasts. Previous work revealed a discrepancy between
      cAMP stimulation and CRE reporter activation of truncated PTH peptides,
      suggesting that additional signaling pathways contribute to activation of the
      CRE. Using a CRE-Luciferase reporter containing multiple copies of the CRE stably
      transfected into the osteoblastic cell line Saos-2, we tested the ability of
      modulators of alternative pathways to activate the CRE or block the PTH-induced
      activation of the CRE. Activators of non-cyclic AMP pathways, that is, EGF (Akt,
      MAPK, JAK/STAT pathways); thapsigargin (intracellular calcium pathway); phorbol
      myristate acetate (protein kinase C, PKC pathway) induced minor increases in CRE
      luciferase activity alone but induced dramatic synergistic effects in combination
      with PTH. The protein kinase A (PKA) inhibitor H-89 (10 microM) almost completely
      blocked PTH-induced activation of the CRE-reporter. Adenylate cyclase inhibitors
      SQ 22536 and DDA had profound and time-dependent biphasic effects on the CRE
      response. The MAPK inhibitor PD 98059 partially inhibited basal and PTH-induced
      CRE activity to the same degree, while the PKC inhibitor bisindolylmaleimide
      (BIS) had variable effects. The calmodulin kinase II inhibitor KN-93 had no
      significant effect on the response to PTH. We conclude that non-cAMP pathways
      (EGF pathway, calcium pathway, PKC pathway) converge on, and have synergistic
      effects on, the response of a CRE reporter to PTH.

PMID- 19180575
TI  - RPAP3 interacts with Reptin to regulate UV-induced phosphorylation of H2AX and
      DNA damage.
AB  - We have previously reported that Monad, a novel WD40 repeat protein, potentiates
      apoptosis induced by tumor necrosis factor-alpha and cycloheximide. By affinity
      purification and mass spectrometry, RNA polymerase II-associated protein 3
      (RPAP3) was identified as a Monad binding protein and may function with Monad as
      a novel modulator of apoptosis pathways. Here we report that Reptin, a highly
      conserved AAA + ATPase that is part of various chromatin-remodeling complexes, is
      also involved in the association of RPAP3 by immunoprecipitation and confocal
      microscopic analysis. Overexpression of RPAP3 induced HEK293 cells to death after
      UV-irradiation. Loss of RPAP3 by RNAi improved HeLa cell survival after UV
      induced DNA damage and attenuated the phosphorylation of H2AX. Depletion of
      Reptin reduced cell survival and facilitated the phosphorylation on H2AX. These
      results suggest that RPAP3 modulates UV-induced DNA damage by regulating H2AX
      phosphorylation.

PMID- 19180576
TI  - From sextant to GPS: twenty-five years of mapping the genome with ChIP.
AB  - Since its inception, ChIP technology has evolved immensely. Technological
      advances have improved its specificity and sensitivity, its scale has expanded to
      a genome-wide level, and its relative ease of use has made it a virtually
      ubiquitous tool. This year marks the 25th anniversary of the development of ChIP.
      In honor of this milestone, we briefly revisit its history, offer a review of
      recent articles employing ChIP on a genome-wide scale, and lay out our views for
      the future of ChIP.

PMID- 19180577
TI  - The attitude of women toward current and future possibilities of diagnostic
      testing in maternal blood using fetal DNA.
AB  - OBJECTIVE: To determine the opinions of women about the new developments in the
      field of noninvasive prenatal diagnosis (NIPD). METHOD: Prospective study using
      questionnaires in two groups of women: women visiting the University Medical
      Centre Groningen and the Martini Hospital Groningen for the routine fetal anomaly
      ultrasound scan at 20 weeks' gestation and female medical master students.
      RESULTS: Both groups consider NIPD an important asset in the reliable diagnosis
      of fetal aneuploidy and gender-determined genetic disorders, with the exception
      of disorders manifesting themselves later in life. There is a negative response
      as to its application for family balancing. Eighty-two percent of the pregnant
      women and 79% of the medical students responded positively to the question
      whether they consider NIPD an important asset in prenatal care. The statement
      that it is an asset because it enables pregnant women to bear an 'optimal child'
      is strongly rejected by both groups. CONCLUSIONS: NIPD paves the way for
      screening on a large scale. Our survey shows that women feel positive about these
      new possibilities, but find it hard to fully realize the consequences and new
      choices they will be confronted with.

PMID- 19180578
TI  - Assessing discrepant findings between QF-PCR on uncultured prenatal samples and
      karyotyping on long-term culture.
AB  - OBJECTIVE: To assess the prevalence of discrepant results found between
      quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on
      uncultured prenatal samples and karyotyping on long-term culture. METHOD: Results
      of QF-PCR from 1932 amniotic fluid (AF) and 1132 chorionic villus (CV) samples
      collected from September 1999 to February 2008 were analyzed. Nature of
      discrepancies was categorized for normal or abnormal results from uncultured and
      cultured samples. RESULTS: A total of nine (0.8%) discrepant cases were found in
      the CV and six (0.3%) in AF samples. Three abnormal results involving trisomy 18
      or mosaic trisomy 13 showed normal karyotype with one representing complete
      discordance. There were three QF-PCR reports with initial mosaic trisomy 21 and
      five cases involving sex chromosome aneuploidy showing complete trisomy 21 and
      45,X, respectively, after long-term culture. CONCLUSIONS: CV (0.8%) and AF (0.3%)
      samples showed discrepant results after culturing and 40% of discrepancy involved
      the sex chromosomes. QF-PCR on long-term culture was concordant with karyotyping
      results meaning that QF-PCR is technically sound. Discrepant PCR findings in
      uncultured prenatal samples likely arose from mosaicism or preferential cell
      culture. Limitations in abnormal QF-PCR results may be discussed with couples
      before further action.

PMID- 19180579
TI  - Fluorescent polyurethane nanocapsules prepared via inverse miniemulsion: surface
      functionalization for use as biocarriers.
AB  - The functionalization of well-defined PU nanocapsules with an aqueous core
      prepared by performing a polyaddition at the interface of inverse (water-in-oil)
      miniemulsion droplets is demonstrated. The miniemulsion technique involving the
      nanoreactor concept allows one to obtain an encapsulation efficiency as high as
      90% within the nanocapsules. A pH independent fluorescent dye is used as a model
      system for the aqueous core. By varying the molar ratio of the diol to the
      diisocyanate at a fixed surfactant concentration, the shell thickness of the
      nanocapsules can be finely tuned. The carboxy- and amino-functionalized surface
      of the nanocapsules can be tailored by an in-situ carboxymethylation reaction and
      by physical adsorption of a cationic polyelectrolyte, i.e. PAEMA or PEI. The
      increased uptake of amino-functionalized fluorescent nanocapsules by HeLa cells
      clearly demonstrates the potential of the functionalized nanocapsules to be
      successfully exploited as biocarriers.

PMID- 19180580
TI  - Guide to endoscopy of the ileo-anal pouch following restorative proctocolectomy
      with ileal pouch-anal anastomosis; indications, technique, and management of
      common findings.
AB  - Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis is the
      surgical procedure of choice for patients with ulcerative colitis (UC). It is
      also performed in selected patients with familial adenomatous polyposis (FAP). A
      significant proportion of patients will develop pouch dysfunction. Flexible
      pouchoscopy is the most important initial investigation in patients with
      dysfunction. It is also important in UC and FAP surveillance. The aim is to
      provide gastroenterologists with a clear understanding of the technique,
      indications, and diagnostic pitfalls when investigating RPC patients with
      flexible pouchoscopy. Flexible pouchoscopy for the investigation of RPC patients
      with pouch dysfunction has a high diagnostic yield, with most causes of pouch
      dysfunction identifiable during this procedure. The risk of developing dysplasia
      following RPC is low. Surveillance pouchoscopy is only recommended in those with
      FAP, those with a previous history of dysplasia or carcinoma, primary sclerosing
      cholangitis, those with a retained rectal cuff, and those with Type C
      histological changes. Flexible pouchoscopy is a useful first-line investigation
      in patients with pouch dysfunction. It can be performed without sedation and has
      a high diagnostic yield; it is also important as part of surveillance in FAP and
      selected UC patients.

PMID- 19180581
TI  - Impact of perceived stigma on inflammatory bowel disease patient outcomes.
AB  - BACKGROUND: Perceived stigma has been linked to disease outcome in several
      chronic illnesses. Stigmatization of illness often leads to increased
      psychological distress and poorer quality of life. While body stigma has been
      identified as a specific inflammatory bowel disease (IBD) patient concern, no
      study to date has systematically investigated the presence of stigma in IBD or
      its effects on disease course and management. METHODS: Participants were
      recruited online and through the Illinois chapter of the Crohn's & Colitis
      Foundation of America. A screening measure was used to identify an established
      IBD diagnosis. Patients completed the Perceived Stigma Scale in IBS, Inflammatory
      Bowel Disease Questionnaire, Rosenberg Self-Esteem Scale, General Self-Efficacy
      Scale, the Brief Symptom Inventory, and the Rating Form of IBD Patient Concerns.
      RESULTS: A total of 211 patients (156 CD, 55 UC) with a confirmed diagnosis for a
      minimum of 6 months completed the study. Eighty-four percent of participants
      reported perceived stigma. Hierarchical regression demonstrated that perceived
      stigma accounted for 10%-22% of the variance in health-related quality of life
      scores, 4%-16% for psychological distress, 5% for medication adherence, 19% for
      self-esteem, and 8% for self-efficacy. Effect sizes were small, but comparable
      with more traditionally evaluated patient variables. CONCLUSIONS: The majority of
      IBD patients report some perceived stigmatization. These results suggest that
      perceived stigma is a significant predictor of poorer outcomes in patients with
      IBD when controlling for illness and demographic variables. Perceived stigma is a
      potentially important psychosocial factor in IBD patient care and warrants
      further investigation.

PMID- 19180582
TI  - Sonographic fetal weight estimation in prolonged pregnancy: comparative study of
      two- and three-dimensional methods.
AB  - OBJECTIVES: To compare two-dimensional (2D) and three-dimensional (3D) ultrasound
      techniques, including volumetry of fetal thigh, for fetal weight (FW) estimation
      in prolonged pregnancy, and to develop a new FW estimation formula. METHODS: This
      prospective comparative study initially included 176 pregnant women. FW
      estimation was performed at >or= 287 days of gestation within <or= 4 days of
      delivery. Fetal head, abdomen and femur were measured using 2D ultrasound
      techniques, and fetal thigh volume was estimated using 3D techniques. The formula
      of Persson and Weldner (2D) was compared with two 3D formulae published by Lee
      and colleagues. In a subgroup of 63 fetuses, volumetry of the abdomen was
      performed and a new formula was developed; this formula was tested prospectively,
      along with the previously published formulae, on a further 50 women (Test Group).
      RESULTS: In the initial group of 176 pregnancies, the SD of the mean percentage
      error (MPE) was 6.3% for both the 2D Persson and Weldner formula and for the
      better performing 3D formula of Lee et al., but the MPE of this Lee formula
      differed significantly from zero. Significantly more FW estimations were within
      +/- 10% of the birth weight when the 2D formula was used than when the 3D
      formulae were applied. The new formula gave a SD of MPE of 5.6% when applied to
      the data from which it was derived. In the Test Group, the SD of MPE was similar
      for the 2D formula, the second formula of Lee et al. and the new formula, with
      values of 7.0, 7.0 and 7.1, respectively, but only the Persson and Weldner
      formula showed a MPE that did not differ significantly from zero. CONCLUSIONS: FW
      in prolonged pregnancies can be estimated using 2D sonography with the same
      accuracy as with 3D sonography. 3D ultrasound techniques require technically
      advanced and expensive equipment, special operator training and skills, and are
      time consuming. It does not seem reasonable to abandon the 2D ultrasound methods
      in favor of 3D ultrasound imaging for FW estimation.

PMID- 19180584
TI  - Factor structure of the Impact of Event Scale-Revised in two different Peruvian
      samples.
AB  - BACKGROUND: This article studied the factor structure of the Impact of Event
      Scale-Revised (IES-R) in two samples in Peru, i.e., a sample of survivors of a
      fire (N=174) and a university student sample (N=562). METHODS: First,
      confirmatory factor analysis was used to compare nine different models of
      posttraumatic stress disorder symptoms as evaluated by the IES-R in both of the
      samples separately. The model with the best fit in both samples had four
      correlated factors, i.e., Intrusion, Avoidance, Hyperarousal and Sleep
      Disturbance. Second, the degree of factorial invariance of the IES-R was compared
      in both the samples using multiple group confirmatory factor analysis. RESULTS
      AND CONCLUSIONS: The results showed almost no differences between both samples.
      Finally, the results supported the internal consistency, as well as the
      concurrent and convergent validity of the IES-R in Peru.

PMID- 19180583
TI  - Dopamine transporters, D2 receptors, and dopamine release in generalized social
      anxiety disorder.
AB  - BACKGROUND: Dopamine D2 receptor and dopamine transporter (DAT) availability in
      the striatum (STR) have each been reported abnormal in generalized social anxiety
      disorder (GSAD) in studies using single photon emission computerized tomography
      (SPECT). D2 receptors and DAT have not previously been studied within the same
      GSAD subjects, however, and prior GSAD studies have not assessed dopamine release
      or subdivided the STR into functional subregions. METHODS: Unmedicated adults
      with GSAD (N=17) and matched healthy comparison (HC) subjects (N=13) participated
      in this study. Of these, 15 GSAD and 13 HC subjects completed baseline assessment
      of D2 receptor availability using positron emission tomography (PET) with the
      radiotracer [11C]raclopride. Twelve GSAD and 13 HC subjects completed a repeat
      scan after intravenous administration of d-amphetamine to study dopamine release.
      Twelve of the GSAD subjects and 10 of the HC subjects also completed SPECT with
      the radiotracer [123I] methyl 3beta-(4-iodophenyl) tropane-2beta-carboxylate
      ([123I]beta-CIT) to assess DAT availability. RESULTS: GSAD and HC groups did not
      differ significantly in striatal DAT availability, the overall striatal or
      striatal subregion D2 receptor availability at baseline, or change in D(2)
      receptor availability after d-amphetamine. Receptor availability and change after
      d-amphetamine were not significantly associated with severity of social anxiety
      or trait detachment. CONCLUSIONS: These findings do not replicate previous
      findings of altered striatal DAT and D2 receptor availability in GSAD subjects
      assessed with SPECT. The differences from results of prior studies may be due to
      differences in imaging methods or characteristics of samples.

PMID- 19180585
TI  - Outcome of treatment of human HeLa cervical cancer cells with roscovitine
      strongly depends on the dosage and cell cycle status prior to the treatment.
AB  - Exposure of asynchronously growing human HeLa cervical carcinoma cells to
      roscovitine (ROSC), a selective cyclin-dependent kinases (CDKs) inhibitor,
      arrests their progression at the transition between G(2)/M and/or induces
      apoptosis. The outcome depends on the ROSC concentration. At higher dose ROSC
      represses HPV-encoded E7 oncoprotein and initiates caspase-dependent apoptosis.
      Inhibition of the site-specific phosphorylation of survivin and Bad, occurring at
      high-dose ROSC treatment, precedes the onset of apoptosis and seems to be a
      prerequisite for cell death. Considering the fact that in HeLa cells the G(1)/S
      restriction checkpoint is abolished by E7, we addressed the question whether the
      inhibition of CDKs by pharmacological inhibitors in synchronized cells would be
      able to block the cell-cycle in G(1) phase. For this purpose, we attempted to
      synchronize cells by serum withdrawal or by blocking of the mitotic apparatus
      using nocodazole. Unlike human MCF-7 cells, HeLa cells do not undergo G(1) block
      after serum starvation, but respond with a slight increase of the ratio of G(1)
      population. Exposure of G(1)-enriched HeLa cells to ROSC after re-feeding does
      not block their cell-cycle progression at G(1)-phase, but increases the ratio of
      S- and G(2)-phase, thereby mimicking the effect on asynchronously growing cells.
      A quite different impact is observed after treatment of HeLa cells released from
      mitotic block. ROSC prevents their cell cycle progression and cells transiently
      accumulate in G(1)-phase. These results show that inhibition of CDKs by ROSC in
      cells lacking the G(1)/S restriction checkpoint has different outcomes depending
      on the cell-cycle status prior to the onset of treatment.

PMID- 19180586
TI  - Characteristics of outpatient prescriptions for frail Taiwanese elders with long
      term care needs.
AB  - OBJECTIVE: To describe medication prescription patterns and associated factors
      among frail Taiwanese elders with long-term care needs defined as having physical
      or cognitive functioning impairments. DESIGN: Longitudinal observational study
      from July 2001 to June 2002. SETTING: Community and Institutions. PARTICIPANTS:
      Nationally representative samples of 11 338 elders from the 'Assessment of
      National Long-Term Care Need in Taiwan' (ANLTCNT). MEASUREMENTS: National
      identification number for each subject was linked to the National Health
      Insurance (NHI) claims data for outpatient clinic visits, diagnoses and
      medication prescriptions. For point prevalence calculation, the day of maximum
      number of medications prescribed during the study year was used. RESULTS: The
      mean age was 78.2 +/- 7.4 years old, of whom 61% were women. The mean number of
      chronic condition categories was 2.9 +/- 1.8. On average, subjects visited 4.1 +/
      2.5 different healthcare organizations, 7.7 +/- 5.3 different physicians, and
      received 32.9 +/- 26.4 outpatient cares. The mean maximum number of prescriptions
      of the study year was 8.6 +/- 4.3; Eighty-four per cent of our experienced
      polypharmacy (prescribed with > or=5 drugs) and 31% had persistent polypharmacy
      (polypharmacy for > or =181 days). Increased contact with healthcare
      professionals and greater number of chronic condition categories were associated
      with the development of polypharmacy and persistent polypharmacy. CONCLUSION: The
      excessive number of medication prescriptions and high prevalence of polypharmacy
      among frail Taiwanese elders raised major drug-safety concern. Multiple
      healthcare providers and clinic visits were strong correlates of polypharmacy.
      Policies should be directed to encourage the elderly to establish primary care
      relationships and to promote geriatric prescription principles to improve
      clinical managements and outcomes.

PMID- 19180587
TI  - Evolution of drug consumption in a sample of French workers since 1986: the
      'Drugs and Work' study.
AB  - PURPOSE: France is known to have a relatively high prescription rate for
      medicines. Few studies have investigated drug use among a healthy worker
      population. The aim of this study was to describe the changing patterns of drug
      use in French workers since 1986 and to evaluate the impact of programs developed
      to reduce drug consumption. METHOD: A cross-sectional survey has been performed
      every 10 years since 1986 among workers from the Toulouse metropolitan area
      (Southwestern, France) using an anonymous questionnaire given to workers during
      their compulsory annual medical visit. Results of the 2006 survey (2213 workers)
      were compared to those obtained in 1986 and 1996. A multivariate analysis was
      performed to investigate factors associated to the modification of drug use with
      time. RESULTS: During the last ten years, prevalence of overall drug consumption
      decreased (40.7% in 2006 vs. 46.7% in 1996, p < 0.001) in contrast to the
      increase observed between 1986 and 1996. Since 1986, patterns of drug use have
      been modified with a decrease in anti-infectious (OR = 0.24) digestive (OR =
      0.54), psychotropic (OR = 0.54), endocrine (OR = 0.57) and cardiotropic (OR =
      0.68) drug use. In contrast, there was a significant increase in musculosqueletic
      (OR = 2.16) drug use. Whatever the period, overall drug consumption was related
      to age, gender or extraprofessional problems. CONCLUSIONS: This study illustrates
      the changing patterns of drug use in a population of workers during the last 20
      years and underlines the importance of awareness raising campaigns on
      prescription patterns.

PMID- 19180588
TI  - Thoracic cytoreductive surgery and intraoperative hyperthermic intrathoracic
      chemotherapy for pseudomyxoma peritonei.
AB  - BACKGROUND: Pleural dissemination of pseudomyxoma peritonei (PMP) is considered
      an advanced/terminal disease. We review our experience with thoracic
      cytoreductive surgery (CRS) and intraoperative hyperthermic intrathoracic
      chemotherapy (HITHOC) for the treatment of pleural recurrence of PMP following
      previous intraabdominal surgery. PATIENTS AND METHODS: An observational study of
      five patients with pleural dissemination from PMP treated with thoracic CRS and
      intraoperative HITHOC with mitomycin C for 90 min at 41.5 degrees C. RESULTS:
      There were three men. The mean age was 46.5 (10.5) years. Postoperatively, one
      patient developed Grade I, one patient developed Grade III and one patient
      developed Grade IV postoperative complication. Two patients had an unremarkable
      postoperative recovery. Only one patient has died 38 months since treatment from
      abdominal complication of this disease with no evidence of thoracic disease. The
      four surviving patients are still alive 4.6-47.4 months after treatment. Two
      patients have evidence of an intraabdominal recurrence. CONCLUSIONS: Thoracic CRS
      and intraoperative HITHOC is a safe and effective procedure to treat pleural
      dissemination from PMP. Long-term disease-free survival can be achieved from this
      treatment for which no other potentially curative therapy has been described.

PMID- 19180589
TI  - Dihydropyrimidine dehydrogenase mRNA expression in peripheral blood of rectal
      cancer patients is significantly associated with residual tumor and distant
      metastases following resection.
AB  - BACKGROUND: DPD and TS expression have been shown to correlate with response of 5
      FU based chemotherapy in colorectal cancer tissue. Little is known about mRNA
      expression levels of TS and DPD in peripheral blood. The goals of this study were
      to test the feasibility of DPD and TS detection in blood and their associations
      to TNM staging and complete surgical resection. METHODS: Whole blood was drawn 1
      day pre- and 10 days post-operatively from 23 patients with rectal cancer. Either
      adjuvant (n = 15) or neoadjuvant (n = 8) treatment was performed. Tumor cells
      were enriched from whole blood by density gradient centrifugation prior to
      extraction of total cellular RNA and subsequent direct quantitative reverse
      transcriptase-PCR assays. RESULTS: DPD was detectable in 21/23 patients (91.3%)
      and TS in 14/23 (61.7%). Stepwise multiple linear regression models showed a
      significant association of DPD expression with distant metastases (P = 0.004) and
      residual tumor categories (P = 0.03). CONCLUSIONS: Quantitative analysis of TS
      and DPD mRNA expression in peripheral blood of rectal cancer patients is
      technically feasible. DPD expression levels appear to be associated with residual
      tumor categories and might serve as a molecular marker for complete tumor
      resection. Larger studies seem to be warranted to scrutinize our hypothesis.

PMID- 19180590
TI  - Personal exposure to mobile communication networks and well-being in children--a
      statistical analysis based on a functional approach.
AB  - The MobilEe-study was the first cross-sectional population-based study to
      investigate possible health effects of mobile communication networks on children
      using personal dosimetry. Exposure was assessed every second resulting in 86,400
      measurements over 24 h for each participant. Therefore, a functional approach to
      analyze the exposure data was considered appropriate. The aim was to categorize
      exposure taking into account the course of the measurements over 24 h. The
      analyses were based on the 480 maxima of each 3 min time interval. Exposure was
      classified using a nonparametric functional method. Heterogeneity of a sample of
      functional data was assessed by comparing the functional mode and mean of the
      distribution of a functional variable. The partition was built within a
      descending hierarchical method. The resulting exposure groups were compared with
      categories derived from a standard method, which used the average exposure over
      24 h and set the cut-off at the 90th percentile. The functional classification
      resulted in a splitting of the exposure data into two groups. Plots of the mean
      curves showed that the groups could be interpreted as children with "low
      exposure" (88%) and "higher exposure" (12%). These groups were comparable with
      categories of the standard method. No association between the categorized
      exposure and well-being was observed in logistic regression models. The
      functional classification approach yielded a plausible partition of the exposure
      data. The comparability with the standard approach might be due to the data
      structure and should not be generalized to other exposures.

PMID- 19180591
TI  - Divergent electronic structures of isoelectronic metalloclusters: tungsten(II)
      halides and rhenium(III) chalcogenide halides.
AB  - Same but different: DFT calculations on hexanuclear tungsten(II) halide clusters
      [W(6)X(8)X'(6)](2-) (X, X'=Cl, Br, I) indicate a breakdown in the isoelectronic
      analogy between themselves and the isostructural rhenium(III) chalcogenide
      clusters [Re(6)S(8)X(6)](4-) (see figure).The hexanuclear tungsten(II) halide
      clusters and the sulfido-halide clusters of rhenium(III) are subsets of a broad
      system of 24-electron metal-metal bonded assemblies that share a common
      structure. Tungsten(II) halide clusters and rhenium(III) sulfide clusters
      luminesce from triplet excited states upon ultraviolet or visible excitation;
      emission from both cluster series has been extensively characterized elsewhere.
      Reported here are density-functional theory studies of the nine permutations of
      [W(6)X(8)X'(6)](2-) (X, X'=Cl, Br, I). Ground-state properties including
      geometries, harmonic vibrational frequencies, and orbital energy-level diagrams,
      have been calculated. Comparison is made to the sulfide clusters of rhenium(III),
      of which [Re(6)S(8)Cl(6)](4-) is representative. [W(6)X(8)X'(6)](2-) and
      [Re(6)S(8)Cl(6)](4-) possess disparate electronic structures owing to the greater
      covalency of the metal-sulfur bond and hence of the [Re(6)S(8)](2+) core. Low
      lying virtual orbitals are raised in energy in [Re(6)S(8)Cl(6)](4-) with the
      result that the LUMO+7 (or LUMO+8 in some cases) of tungsten(II) halide clusters
      is the LUMO of [Re(6)S(8)Cl(6)](4-) species. An inversion of the HOMO and HOMO-1
      between the two cluster series also occurs. Time-dependent density-functional
      calculations using asymptotically correct functionals do not recapture the
      experimentally observed periodic trend in [W(6)X(14)](2-) luminescence (E(em)
      increasing in the order [W(6)Cl(14)](2-) < [W(6)Br(14)](2-) < [W(6)I(14)](2-)),
      predicting instead that emission energies decrease with incorporation of the
      heavier halides. This circumstance is either a gross failure of the time
      dependent formalism of DFT or it indicates extensive multistate emission in
      [W(6)X(8)X'(6)](2-) clusters. The inapplicability of isoelectronic analogies
      between clusters of Group 6 and Group 7 is emphasized.

PMID- 19180592
TI  - Stereo- and regioselectivity in an intramolecular nitrone-alkene cycloaddition of
      hept-6-enoses with a trans-acetonide blocking group.
AB  - From sugar to cycloadduct: The effect of the trans-acetonide blocking group and
      the stereochemistry of the substituents on the regio- and stereoselectivity in
      the intramolecular nitrone-alkene cycloaddition (INAC) reaction of hept-6-enoses
      (see scheme) is reported and studied by using theoretical analysis.The positional
      effect of the trans-acetonide blocking group and the effect of the
      stereochemistry of the substituents on the regio- and stereoselectivity in
      intramolecular nitrone-alkene cycloaddition (INAC) reactions of hept-6-enoses are
      reported. Hept-6-enoses with a 2,3-trans-acetonide group were reacted with N
      alkyl hydroxylamine to give a mixture of exo and endo cycloadducts (cyclohexanols
      and cycloheptanols, respectively). Complete formation of endo cycloadducts
      (cycloheptanols) was realized for the INAC reaction of hept-6-enoses containing a
      3,4-trans-O-isopropylidene ring. Similarly, reaction of a hept-6-enose possessing
      a 4,5-trans-acetonide group surprisingly afforded exo cycloadducts
      (cyclohexanols) exclusively. The regio- and stereochemical outcomes of these
      reactions were rationalized on the basis of transition-state energies obtained by
      computation.

PMID- 19180593
TI  - Reactivity of thiosemicarbazides with redox active metal ions: controlled
      formation of coordination complexes versus heterocyclic compounds.
AB  - The reactions of 1,1-dimethyl-4-phenylthiosemicarbazide (LH) with Cu(II) and
      Sn(IV) have been investigated. If THF or methanol is used as solvent with Cu(II),
      oxidative cyclisation and coupling are observed, yielding a 1,2,4-thiadiazole or
      a 1,3,4-thiadiazolium salt. SnI(4) is also able to induce oxidative coupling of
      two thiosemicarbazide ligands, yielding 1,2,4-thiadiazolium or 1,2,4-triazolium
      salts, with I(3)(-) as the counterion, depending on the reaction conditions. By
      contrast, reaction of LH with SnI(4) in acetone yields a 1,3-thiazolium salt,
      with I(-) as counterion. Reaction with Cu(II) salts or SnI(4) in basic media
      leads to the formation of metal complexes containing two deprotonated
      thiosemicarbazide ligands. In the reaction of CuCl(2) in water in the presence of
      acid a complex containing two neutral ligands is obtained. Reactions with SnCl(4)
      are not able to induce ligand cyclisation, although a coordination compound with
      two neutral ligands was isolated from methanol.

PMID- 19180594
TI  - Integrated oligoaniline-cross-linked composites of Au nanoparticles/glucose
      oxidase electrodes: a generic paradigm for electrically contacted enzyme systems.
AB  - Sweet sensor: A bis-aniline-cross-linked Au nanoparticles (NPs)/glucose oxidase
      composite has been electropolymerized on a Au electrode (see picture). The
      integrated Au NPs/enzyme electrode provides an effective matrix for making
      electrical contact with the enzyme, and this yields a specific amperometric
      glucose biosensor.Electropolymerizable glucose oxidase (GOx) was synthesized by
      the tethering of thioaniline units to the protein. The electropolymerization of
      the thioaniline-modified GOx in the presence of thioaniline-functionalized Au
      nanoparticles (NPs) yielded a three-dimensional bis-aniline-cross-linked Au
      NPs/GOx network. The bis-aniline bridging units are redox active and mediate the
      electron transfer between the enzyme redox sites and the electrode, and the Au
      NPs provide the three-dimensional conductivity for transporting the electrons to
      the electrode. The covalently linked GOx displays an effective electrical contact
      with the electrode (turnover rate of ca. 500 s(-1)), which results in a sensitive
      and selective glucose-sensing electrode. The preparation of the electrode by
      means of electropolymerization, and the bioelectrocatalytic features of the
      electrode, suggest its feasibility as a miniaturized electrode with a sensing
      matrix and as an implantable glucose sensor in future applications.

PMID- 19180595
TI  - Two-way molecular switches with large nonlinear optical contrast.
AB  - Molecular switches: Highly efficient acido- and photoswitchable frequency
      doublers (see scheme) based on the indolinooxazolidine core are studied by means
      of hyper-Rayleigh experiments and quantum-chemical calculations.To optimize the
      nonlinear optical (NLO) contrast, a series of indolinooxazolidine derivatives
      with electron-withdrawing substituents in the para position on the indolinic
      residue have been synthesized. Their linear and nonlinear optical properties have
      been characterized by UV-visible absorption and hyper-Rayleigh scattering
      measurements, as well as by ab initio calculations. The two-way photo- or pH
      triggered switching mechanism has been demonstrated by comparing the absorption
      spectra of the zwitterionic and protonated open forms (POF). Hyper-Rayleigh
      measurements have revealed that the second-order NLO contrast between the closed
      indolinooxazolidine and the open pi-conjugated colored forms remain very large
      upon substitution. Theory and measurements show that for the POFs the amplitude
      of the first hyperpolarizability follows the Hammett parameters of the
      withdrawing groups. However, because the measurements are performed in resonance,
      to recover this behavior, elaborate procedures including homogeneous and
      inhomogeneous broadenings, as well as single-mode vibronic structures are
      necessary to extrapolate to the static limit.

PMID- 19180596
TI  - Protonation of 2H-azaphosphirene complexes: P-N bond activation and ring
      expansion reactions.
AB  - P-N bond activation of 2H-azaphosphirene complexes 1 and 2 by using triflic acid
      led to ring expansion in the presence of nitriles. In the absence of nitriles,
      the reaction surprisingly afforded two haptomeric N-protonated 1-aza-3-phospha
      butadiene complexes in the case of complex 1, whereas the N-protonated 2H
      azaphosphirene complex [H-2](+) was characterized by NMR spectroscopy.Protonation
      of 2H-azaphosphirene complexes 1 and 2 using trifluoromethanesulfonic acid in the
      presence and in the absence of nitriles was studied. Reactions with nitrile
      derivatives of different nucleophilicity and steric demand (3 a-f) led to highly
      bond- and regioselective ring-expansion reactions of complexes 1 and 2 and
      yielded 2H-1,4,2-diazaphosphole complexes 4 a-f and 5 a after deprotonation with
      NEt(3). Upon protonation of complex 1 in the absence of nitriles a mixture of two
      haptomeric N-protonated 1-aza-3-phosphabuta-1,3-diene complexes 13 and 14 was
      obtained, which upon addition of Me(2)NCN (3 a) and NEt(3) afforded 2H-1,4,2
      diazaphosphole complex 16 a bearing a P-substituent with only one SiMe(3) group.
      Protonation of complex 2 led to the 2H-azaphosphirenium complex [H-2](+),
      unambiguously identified by NMR spectroscopy at low temperature. All isolated
      products were characterized by multinuclear NMR spectroscopy, IR, MS, and single
      crystal X-ray crystallography in the cases of complexes 4 a, 4 e, 6 a, and 16 a.
      Furthermore, ESI-MS/MS studies on primarily formed reactive intermediates and DFT
      studies on the reaction mechanism are presented.

PMID- 19180597
TI  - Self-assembly of high-nuclearity copper cages: tricorne Cu21 and saddlelike
      cyclic Cu16.
AB  - Reaction of cupric salts with H(2)Rppz (R = H, Me; H(2)ppz = 3-(2
      hydroxyphenyl)pyrazole; H(2)Meppz = 3-(2-hydroxy-5-methylphenyl)pyrazole) in the
      presence of sodium azide and triethylamine as bases gave two high-nuclearity
      copper cage compounds [HNEt(3)](2)[Cu(21)(CH(3)CN)(2)(H(2)O)(mu(2)-N(3))(6)(mu(3)
      N(3))(2)(ppz)(18)](H(2)O)(3)(EtOH)(2) (1) and
      [Cu(16)(EtOH)(2)(H(2)O)(2)(Meppz)(16)]9.5 H(2)O (2), respectively. X-ray
      crystallographic studies revealed that molecular skeletons of 1 and 2 are unique
      tricorne Cu(21) and saddlelike cyclic Cu(16) aggregates, respectively. The
      magnetic properties studies showed overall antiferromagnetic interactions in 1
      and 2. Quantum Monte Carlo simulations by using a 3-J model for 1 and a 2-J model
      for 2 were performed, which indicated that the magnetic couplings within the
      triangular copper units in 1 are ferromagnetic and those between other copper
      ions are antiferromagnetic, whereas in 2 all magnetic couplings between adjacent
      copper ions are exclusively antiferromagnetic.

PMID- 19180598
TI  - Chloride-free method to synthesise new ionic liquids with mixed borate anions.
AB  - Chloride avoided! A new chloride-free method to synthesise ionic liquids (ILs)
      with mixed borate anions, starting from tetrafluoroborate compounds, has been
      developed and a number of examples including some new ILs are presented (see
      scheme; [CAT](+) = cation). It is widely applicable and allows access to mixed
      borates with various types of ligands in a straightforward manner.

PMID- 19180599
TI  - Binding of ionic species: a general approach to measuring binding constants and
      assessing affinities.
AB  - Bound together: The association of receptors with ionic species cannot be
      assimilated to the binding of neutral guests. When dealing with salts, both ion
      pairing and binding to the free and the ion-paired ionic guest determine the
      actual association pattern (see figure). The general issue of measuring
      association constants and assessing affinities for ions is addressed and
      validated in two cases of anion binding.A general approach to the largely
      underestimated issue of measuring binding constants and assessing affinities in
      the binding of ionic species is described. The approach is based on a rigorous,
      nongraphical determination of binding constants in multiequilibrium systems by
      nonlinear regression of chemical shift data from NMR titrations and on the use of
      the BC(50) descriptor for assessing affinities and ranking the binding ability of
      receptors on a common scale. The approach has been validated with two tripodal
      anion-binding receptors, namely, a ureidic (1) and a pyrrolic (2) receptor,
      binding to tetramethylammonium chloride in CDCl(3)/CD(3)CN (80:20). A set of five
      and six formation constants could be measured for 1 and 2, respectively,
      including, in addition to the ion pair, complexes of the free and the ion-paired
      anion. The BC(50) values calculated from the measured constants allowed a
      quantitative assessment of each receptor's binding affinity towards the chloride
      anion, the pyrrolic receptor showing a 15-fold larger affinity over the ureidic
      receptor, a figure that quantifies the improvement obtained by replacing the
      amido-pyrrolic for ureidic binding groups on the tripodal scaffold of the
      receptor. The results have shown that, in contrast to common practice, neither of
      the two systems could be appropriately described by a 1:1 association with the
      anion only, but required the ion-pairing and ion-pair binding equilibria to be
      taken into account because these contribute substantially to the complexation
      process. The BC(50) descriptor has also been shown to be a useful and general
      tool for the assessment of affinities of systems involving ionic species. The
      required extension of the BC(50) binding descriptor to include the treatment of
      ion-binding has been described in detail.

PMID- 19180600
TI  - Environmentally benign production of biodiesel using heterogeneous catalysts.
AB  - Fuelling the future: The production of esters of higher fatty acids from plant
      materials is of great interest for the manufacture of biodiesel. Heterogeneous
      catalysts can provide new routes for the environmentally benign production of
      biodiesel. Particulate heterogeneous catalysts can be readily separated from
      products following reaction allowing the catalyst to be reused, generating less
      waste, and consuming less energy. Diesel engines are simple and powerful, and
      exhibit many advantages in energy efficiency and cost. Therefore, the production
      of higher fatty acid esters from plant materials has become of interest in recent
      years for the manufacture of biodiesel, a clean-burning alternative fuel. The
      industrial production of biodiesel mostly proceeds in the presence of "soluble"
      catalysts such as alkali hydroxides and liquid acids. A considerable amount of
      energy is required for the purification of products and catalyst separation, and
      furthermore these catalysts are not reusable. This process results in substantial
      energy wastage and the production of large amounts of chemical waste. Particulate
      heterogeneous catalysts can be readily separated from products following
      reaction, allowing the catalyst to be reused and consuming less energy. This
      Minireview describes the environmentally benign production of biodiesel using
      heterogeneous catalysts such as solid bases, acid catalysts, and immobilized
      enzymes.

PMID- 19180601
TI  - Novel polymeric materials from vegetable oils and vinyl monomers: preparation,
      properties, and applications.
AB  - Veggie-based products: Vegetable-oil-based polymeric materials, prepared by free
      radical, cationic, and olefin metathesis polymerizations, range from soft rubbers
      to ductile or rigid plastics, and to high-performance biocomposites and
      nanocomposites. They display a wide range of thermophysical and mechanical
      properties and may find promising applications as alternatives to petroleum-based
      polymers.Vegetable oils are considered to be among the most promising renewable
      raw materials for polymers, because of their ready availability, inherent
      biodegradability, and their many versatile applications. Research on and
      development of vegetable oil based polymeric materials, including thermosetting
      resins, biocomposites, and nanocomposites, have attracted increasing attention in
      recent years. This Minireview focuses on the latest developments in the
      preparation, properties, and applications of vegetable oil based polymeric
      materials obtained by free radical, cationic, and olefin metathesis
      polymerizations. The novel vegetable oil based polymeric materials obtained range
      from soft rubbery materials to ductile or rigid plastics and to high-performance
      biocomposites and nanocomposites. These vegetable oil based polymeric materials
      display a wide range of thermophysical and mechanical properties and should find
      useful applications as alternatives to their petroleum-based counterparts.

PMID- 19180602
TI  - A versatile methodology for the synthesis of alpha,beta-unsaturated 3
      iminophosphines.
AB  - Phorteen phine phosphines: Fourteen new alpha,beta-unsaturated beta-chloroimines
      were synthesized from inexpensive ketones by using the Vilsmeier-Haack reagent
      followed by Schiff-base condensation. Each imine was subsequently converted to an
      alpha,beta-unsaturated 3-iminophosphine through either late-metal-catalyzed
      phosphorus-carbon cross-coupling or through an addition-elimination sequence (see
      scheme). This high-yield protocol serves as a general means to produce alpha,beta
      unsaturated 3-iminophosphines.Fourteen new alpha,beta-unsaturated beta
      chloroimines were synthesized from commercially available ketones using the
      Vilsmeier-Haack reagent, followed by Schiff-base condensation. Each imine was
      subsequently converted to an alpha,beta-unsaturated 3-iminophosphine through
      either late-metal-catalyzed phosphorus-carbon cross-coupling or through an
      addition-elimination sequence. Depending on the substituents present on the vinyl
      group, the resultant phosphines were isolated as either E or Z diastereomers with
      successful isolation of predominately single diastereomers for all fourteen new
      phosphines investigated. Full synthetic and spectroscopic details, as well as
      several X-ray crystal structures of these new imines and phosphines, are reported
      in addition to X-ray crystal structures of related palladium complexes.

PMID- 19180603
TI  - Highly diastereoselective addition of allyltitanocenes to ketones.
AB  - A route with less congestion: A practical method for the highly
      diastereoselective preparation of anti tertiary homoallylic alcohols has been
      developed. The reaction of allyltitanocenes, generated by the reductive
      titanation of various allylic substrates with a titanocene(II) species, with a
      variety of ketones produced the anti tertiary homoallylic alcohols in good
      diastereoselectivity, even when using sterically less congested ketones (see
      scheme; Cp: cyclopentadienyl; Piv: pivaloyl).The reaction of allyltitanocenes,
      generated by the reductive titanation of allylic sulfides or allylic alcohol
      derivatives with a titanocene(II) species, with phenyl and sterically hindered
      alkyl methyl ketones produced anti tertiary homoallylic alcohols with complete
      diastereoselectivity. Even when sterically less congested methyl ethyl ketone and
      methyl vinyl ketone were employed, the anti homoallylic alcohols were obtained
      with unprecedented high diastereoselectivity. The observed anti selectivity
      suggests that the reaction proceeds by the addition of primary (E)-sigma
      allyltitanocenes to ketones through chairlike cyclic transition states.

PMID- 19180604
TI  - Asymmetric iminium ion catalysis with a novel bifunctional primary amine
      thiourea: controlling adjacent quaternary and tertiary stereocenters.

PMID- 19180605
TI  - Stereoselective synthesis of 2,6-disubstituted piperidines using the iridium
      catalyzed allylic cyclization as configurational switch: asymmetric total
      synthesis of (+)-241 d and related piperidine alkaloids.
AB  - Pressing the configurational switch: Use of enantiomeric Ir catalysts allows the
      vinylpiperidine building blocks 2 a and 2 b to be synthesized with high
      selectivity. Total syntheses of the dendrobate alkaloid (+)-241 D, its C6-epimer,
      and a spruce alkaloid are presented as applications.

PMID- 19180606
TI  - ortho-Selective phenol-coupling reaction by anodic treatment on boron-doped
      diamond electrode using fluorinated alcohols.
AB  - Enlarged scope by fluorinated mediators: Oxyl radicals are easily formed on boron
      doped diamond (BDD) electrodes and can be exploited for the ortho-selective
      coupling to the corresponding biphenols (see scheme). At partial conversion, a
      clean transformation is achieved that can be applied to electron-rich as well as
      fluorinated phenols.

PMID- 19180607
TI  - Helical hairpin structure of a potent antimicrobial peptide MSI-594 in
      lipopolysaccharide micelles by NMR spectroscopy.
AB  - Essential understanding: Elucidation of structural requirements and interactions
      of antimicrobial peptides with lipopolysaccharide (LPS) are essential to
      understand the mechanism of action of antimicrobial peptides. The highly active
      antimicrobial peptide MSI-594 (see figure for electrostatic potential surface)
      acquires a novel helical hairpin structure in complex with LPS. The structure and
      interactions of MSI-594 with LPS presented here provide important insights into
      the mechanism of outer membrane permeabilization by antimicrobial peptides.

PMID- 19180608
TI  - A binuclear Cu(II) metallacycle capable of discerning between pyrazine and its
      different methyl-substituted derivatives based on reversible intracage metal
      ligand binding.
AB  - Squashy cage: A flexible, spongelike, and reversible metal-binding Cu(2)L(2) cage
      that can adjust its internal space in response to pyrazine and its derivatives
      based on a recognition sequence of pyrazine, 2,5-dimethylpyrazine, and 2
      methylpyrazine (see figure) is described.

PMID- 19180609
TI  - Synthesis of cellulose fatty esters as plastics-influence of the degree of
      substitution and the fatty chain length on mechanical properties.
AB  - Alternative films: The effect of the chain length and the degree of substitution
      on the mechanical and hydrophobic properties of various cellulose fatty ester
      plastic films was studied. The results suggest that the cellulose ester plastic
      films are promising alternatives to petrochemical commodity plastics such as
      polyethylene.Cellulose-based plastic films were prepared by acylating cellulose
      in homogeneous media under microwave irradiation with fatty acyl chlorides
      containing either saturated or unsaturated chains of various lengths (C(12) to
      C(18)). The resultant cellulose esters were analysed by FTIR and (1)H NMR
      spectroscopy to confirm their structure and to determine their degree of
      substitution. Some of the cellulose fatty esters were then converted into polymer
      films by casting. The mechanical properties of these films were determined,
      including their elastic modulus, tensile strength and tensile strain level. The
      hydrophobicity of the polymer films was determined by contact angle measurement
      with water. The mechanical and hydrophobic properties of the plastic films were
      then compared to those of commodity plastics.

PMID- 19180610
TI  - Reaction of a metallamacrocycle leading to a
      mercury(II)...palladium(II)...mercury(II) interaction.
AB  - All wrapped up: The reaction of a 22-membered macrocycle derived from bis(o
      formylphenyl)mercury and 1,2-phenylenediamine with palladium(II) results in
      cleavage of the macrocycle and concomitant formation of a trimetallic complex
      (see picture; phenyl rings truncated for clarity). The nature of the
      Hg(II)...Pd(II)...Hg(II) interaction was investigated by theoretical studies.

PMID- 19180611
TI  - Synthesis of pure phosphorus nanostructures.
AB  - To Bi or not to Bi? The synthesis of phosphorus nanorods of two differing
      morphologies is reported, in both the presence and absence of a bismuth catalyst.
      Not only do these materials represent a new class of elemental nanorods but they
      also give valuable insight into the complex allotropy of phosphorus.

PMID- 19180612
TI  - Formation of patches on 3D SAMs driven by thiols with immiscible chains observed
      by ESR spectroscopy.
AB  - Beyond stripes: The extreme lipophobicity of perfluorinated chains attached to
      amphiphilic thiolates triggers the formation of "stars" (or patches) surrounded
      by amphiphilic alkylthiolates in three-dimensional self-assembled monolayers.
      This strategy led to the first example of a water-soluble multicompartment
      monolayer wrapped around a gold core.

PMID- 19180613
TI  - Shape-selective interception by hydrocarbons of the O2-derived oxidant of a
      biomimetic nonheme iron complex.
AB  - Picky ferryl: The complex [Fe(Tp(Ph(2)))(BF)] (Tp(Ph(2)) = hydrotris(3,5
      diphenylpyrazolyl)borate; BF = benzoylformate) reacts with O(2) to generate an
      oxidant (see picture; O red, pink; Fe yellow; N blue; C gray; H white) that
      oxidizes added hydrocarbons shape-selectively. Discrimination derives from a
      cleft formed by two phenyl groups of the Tp(Ph(2)) ligand, favoring oblate
      spheroidal substrates.

PMID- 19180615
TI  - STM insight into hydrogen-bonded bicomponent 1D supramolecular polymers with
      controlled geometries at the liquid-solid interface.
AB  - Bicomponent supramolecular polymers, consisting of two alternating molecules
      bridged through six H-bonds, are observed by STM at the solid-liquid interface.
      Control of the geometry of the 1D architecture was obtained by using two
      different connecting molecules with different conformational rigidity, affording
      either linear (see picture, left) or zigzag (right) motifs.

PMID- 19180614
TI  - Evidence for a stereoelectronic effect in human oxygen sensing.
AB  - How PHDs achieve specificity: trans-4-prolyl hydroxylation of the transcription
      factor HIF occurs with stereochemical retention. Substrate-analogue studies show
      how the von Hippel Lindau tumor suppressor protein (pVHL) and the oxygen-sensing
      hydroxylases (PHDs) achieve specificity for hydroxyprolyl/prolyl residues for the
      C(4)-exo/endo prolyl conformations, respectively.

PMID- 19180616
TI  - Iridium-catalyzed reactions of trifluoromethylated compounds with alkenes: a
      C(sp3)-H bond activation alpha to the trifluoromethyl group.
AB  - Catalytic convenience: The use of iridium or ruthenium catalysts for C(sp(3))-H
      bond activation has led to the addition reaction of trifluoromethylated compounds
      to alkenes (see scheme). This atom-economical reaction occurs under neutral
      reaction conditions and without the formation of undesired defluorinated by
      products, even at high temperature.

PMID- 19180617
TI  - Addition of hydrogen or ammonia to a low-valent group 13 metal species at 25
      degrees C and 1 atmosphere.
AB  - Mild-mannered: The low-valent aryl gallium(I) species :GaAr' (Ar' = 2,6-(2,6
      iPr(2)C(6)H(3))(2)C(6)H(3)) undergoes addition to H(2) or NH(3) at room
      temperature and one atmosphere of pressure to afford 1 or 2 (see scheme), which
      were characterized by X-ray crystallography and NMR and IR spectroscopy.

PMID- 19180618
TI  - Total synthesis of the antiviral peptide antibiotic feglymycin.
AB  - An adaptable approach: The first highly convergent stereoselective synthesis of
      feglymycin (see structure) and its enantiomer is based on the coupling of
      repeating peptide fragments. The use of weakly basic conditions throughout the
      synthesis suppressed the epimerization of sensitive aryl glycine units.
      Feglymycin has strong anti-HIV activity as well as potent (previously identified
      as weak) antibacterial activity against Staphylococcus aureus.

PMID- 19180619
TI  - Magnesium borohydride confined in a metal-organic framework: a preorganized
      system for facile arene hydroboration.
AB  - In close quarters: When confined in a metal-organic framework, magnesium
      borohydride reacts with arenes by a hydroboration pathway (see scheme), in
      contrast to its reactivity under analogous homogeneous solution-phase conditions.
      Framework-imposed organization of the reactive groups is required, which is
      achieved by a combination of the metal coordination and two hydrogen bonds.

PMID- 19180620
TI  - A bistable poly[2]catenane forms nanosuperstructures.
AB  - Side-chain poly[2]catenanes at the click of a switch! A bistable side-chain
      poly[2]catenane has been synthesized and found to form hierarchical self
      assembled hollow superstructures of nanoscale dimensions in solution. Molecular
      electromechanical switching (see picture) of the material is demonstrated, and
      the ground-state equilibrium thermodynamics and switching kinetics are examined
      as the initial steps towards processible molecular-based electronic devices and
      nanoelectromechanical systems.

PMID- 19180621
TI  - Semisynthesis of a homogeneous glycoprotein enzyme: ribonuclease C: part 2.
AB  - Active RNase glycoprotein from three pieces: The glycoprotein enzyme ribonuclease
      C, which contains a complex saccharide N-glycan, was synthesized by sequential
      native chemical ligation. An optimized ligation and isolation protocol allowed
      the efficient assembly and refolding of the 124 amino acid enzyme.

PMID- 19180622
TI  - A luminescent microporous metal-organic framework for the fast and reversible
      detection of high explosives.
AB  - Sensors and sensitivity: A highly luminescent microporous metal-organic
      framework, [Zn(2)(bpdc)(2)(bpee)] (bpdc = 4,4'-biphenyldicarboxylate; bpee = 1,2
      bipyridylethene), is capable of very fast and reversible detection of the vapors
      of the nitroaromatic explosive 2,4-dinitrotoluene and the plastic explosive
      taggant 2,3-dimethyl-2,3-dinitrobutane, through redox fluorescence quenching with
      unprecedented sensitivity (see spectra).

PMID- 19180623
TI  - Trapping of a thiolate-->dibromine charge-transfer adduct by a macrocyclic
      dinickel complex and its conversion into an arenesulfenyl bromide derivative.
AB  - Stuck on sulfur: The first transition-metal complexes with S-Br units are
      surprisingly stable. Solid 3 is stable for at least six months and under vacuum
      solid 2 does not lose Br(2). The formation of the first structurally
      characterized transition-metal arenesulfenyl bromide complex 3 occurs with a
      change of the spin ground state from S = 2 to S = 0.

PMID- 19180624
TI  - C-F activation at rhodium boryl complexes: formation of 2-fluoroalkyl-1,3,2
      dioxaborolanes by catalytic functionalization of hexafluoropropene.
AB  - Fluorinated building blocks by C-F bond cleavage: Catalytic C-F activation
      reactions that give novel dioxaborolanes have been developed (see scheme). The
      reactions proceed at room temperature, and catalytic intermediates are presumably
      rhodium hydride and boryl species.

PMID- 19180625
TI  - Prenatal diagnosis of Gollop-Wolfgang complex (tibial agenesis and femoral
      bifurcation).

PMID- 19180627
TI  - Concurrent release of admixed antimicrobials and salicylic acid from salicylate
      based poly(anhydride-esters).
AB  - A polymer blend consisting of antimicrobials (chlorhexidine, clindamycin, and
      minocycline) physically admixed at 10% by weight into a salicylic acid-based poly
      (anhydride-ester) (SA-based PAE) was developed as an adjunct treatment for
      periodontal disease. The SA-based PAE/antimicrobial blends were characterized by
      multiple methods, including contact angle measurements and differential scanning
      calorimetry. Static contact angle measurements showed no significant differences
      in hydrophobicity between the polymer and antimicrobial matrix surfaces. Notable
      decreases in the polymer glass transition temperature (T(g)) and the
      antimicrobials' melting points (T(m)) were observed indicating that the
      antimicrobials act as plasticizers within the polymer matrix. In vitro drug
      release of salicylic acid from the polymer matrix and for each physically admixed
      antimicrobial was concurrently monitored by high pressure liquid chromatography
      during the course of polymer degradation and erosion. Although the
      polymer/antimicrobial blends were immiscible, the initial 24 h of drug release
      correlated to the erosion profiles. The SA-based PAE/antimicrobial blends are
      being investigated as an improvement on current localized drug therapies used to
      treat periodontal disease.

PMID- 19180628
TI  - Large differences in patterns of breast cancer survival between Australia and
      England: a comparative study using cancer registry data.
AB  - Survival from breast cancer in the UK is lower than in other countries in Western
      Europe, the USA and Australia. However, these international differences have not
      yet been examined in relation to tumor characteristics, treatment, screening
      history or other prognostic factors. We calculated relative survival by age,
      period of diagnosis, category of unemployment and extent of disease for women
      diagnosed with breast cancer during the period 1980-2002 in New South Wales
      (Australia) and West Midlands (England). National cancer registry data for each
      country for the period 1990-1994 were also examined. The excess hazard ratio was
      modeled as a function of prognostic covariables. Survival in Australia and New
      South Wales was higher than in England and West Midlands, respectively. In both
      regions, survival was lower for more deprived women and for the elderly. These
      differences were greater in West Midlands. Survival from localized and regional
      disease in New South Wales was higher than in West Midlands, but survival from
      metastatic disease was similar. Differences in breast cancer survival are
      unlikely to be entirely due to differences in data quality or to limitations of
      the analyses, although the measure of extent of disease used may not have been
      adequate to elucidate the effect of stage fully. One possible causal explanation
      is that the management of breast cancer differs between these regions. Further
      research should acquire better data on stage and investigate the effect of
      comorbidity and of patterns of care upon the difference in breast cancer survival
      between England and Australia.

PMID- 19180629
TI  - Foetal craniopharyngioma diagnosed by prenatal ultrasonography and confirmed by
      histopathological examination.
AB  - BACKGROUND: Craniopharyngioma is an intracranial tumour, which usually develops
      in children and young adults and rarely occurs in intrauterine life. METHODS: In
      foetal life, ultrasonography and later computed tomography (CT) and magnetic
      resonance imaging (MRI) are regarded to be the most effective tools of diagnosis.
      RESULTS: In the seven cases published earlier, tumour size was below our finding
      of 96 x 80 x 65 mm(3). In relation to the current case report, we aimed at
      surveying the available information on prenatal craniopharyngioma. CONCLUSION:
      Although the tumour is benign, the neurological and ophthalmologic complications,
      arising due to its expansive growth, are suggestive of a poor prognosis. Despite
      the high mortality and morbidity rates, neurosurgical treatment appears to be the
      sole option.

PMID- 19180630
TI  - Economic and policy decisions in prenatal screening.

PMID- 19180631
TI  - Down syndrome screening: determining the cutoff level of risk for invasive
      testing.

PMID- 19180632
TI  - Review of published studies of kidney, liver, and gastrointestinal birth defects
      in fetal alcohol spectrum disorders.
AB  - OBJECTIVE: Review of published studies of birth defects of the renal, liver, and
      gastrointestinal organ systems in subjects with fetal alcohol spectrum disorders
      (FASD). METHOD: We searched PubMed (http://www.pubmed.gov) using the following
      terms: fetal alcohol syndrome and: gastrointestinal tract, kidney, liver, and
      congenital abnormalities for all years and English only citations. RESULTS: We
      located 12 studies of FASD and defects of or functional impairments for the
      liver, 12 of renal abnormalities, and only two with gastrointestinal defects. We
      did not identify specific patterns of malformations or functional deficits for
      any of the three organ systems. The existing literature suggests a series of
      nonspecific outcomes in FASD. CONCLUSIONS: Fetal alcohol spectrum disorder
      includes a diagnostic category of alcohol-related birth defects which is
      clinically difficult to apply. This study adds to the existing literature on
      birth defects in FASD which is still very limited. The categorical diagnosis of
      alcohol-related birth defects requires additional research to determine if a
      specific pattern of organ specific abnormalities or functional deficits emerges
      in subjects with FASD.

PMID- 19180633
TI  - Comparative study of clinical characteristics of amniotic rupture sequence with
      and without body wall defect: further evidence for separation.
AB  - BACKGROUND: Amniotic rupture sequence (ARS) is a disruption sequence presenting
      with fibrous bands, possibly emerging as a result of amniotic tear in the first
      trimester of gestation. Our comparative study aims to assess whether there is a
      difference in the clinical pattern of congenital limb and internal organ
      anomalies between ARS with body wall defect (ARS-BWD) and ARS without BWD (ARS
      L). METHODS: Among 1,706,639 births recorded between 1998 and 2006, 50 infants
      with a diagnosis of ARS were reported to the Polish Registry of Congenital
      Malformations. The information on 3 infants was incomplete, thus only 47 cases
      were analyzed. These infants were classified into groups of ARS-L (38 infants)
      and ARS-BWD (9 infants). RESULTS: The ARS-BWD cases were more frequently affected
      by various congenital defects (overall p < 0.0001), and in particular by
      urogenital malformations (p = 0.003). In both groups, limb reduction defects
      occurred in approximately 80% of cases; however, minor and distal limb defects
      (phalangeal or digital amputation, pseudosyndactyly, constriction rings)
      predominated in the ARS-L group (p = 0.0008). The ARS-L group also had a higher
      frequency of hand and upper limb involvement. CONCLUSIONS: This observation
      suggests that amniotic band adhesion in ARS-L takes place at a later development
      stage. Although limited by a small sample size, our study contributes to the
      growing evidence that both ARS entities represent two nosologically distinct
      conditions.

PMID- 19180634
TI  - Targeted mechanical properties for optimal fluid motion inside artificial bone
      substitutes.
AB  - Our goal was to develop a method to identify the optimal elastic modulus,
      Poisson's ratio, porosity, and permeability values for a mechanically stressed
      bone substitute. We hypothesized that a porous bone substitute that favors the
      transport of nutriments, wastes, biochemical signals, and cells, while keeping
      the fluid-induced shear stress within a range that stimulates osteoblasts, would
      likely promote osteointegration. Two optimization criteria were used: (i) the
      fluid volume exchange between the artificial bone substitute and its environment
      must be maximal and (ii) the fluid-induced shear stress must be between 0.03 and
      3 Pa. Biot's poroelastic theory was used to compute the fluid motion due to
      mechanical stresses. The impact of the elastic modulus, Poisson's ratio,
      porosity, and permeability on the fluid motion were determined in general and for
      three different bone substitute sizes used in high tibial osteotomy. We found
      that fluid motion was optimized in two independent steps. First, fluid transport
      was maximized by minimizing the elastic modulus, Poisson's ratio, and porosity.
      Second, the fluid-induced shear stress could be adjusted by tuning the bone
      substitute permeability so that it stayed within the favorable range of 0.03 to 3
      Pa. Such method provides clear guidelines to bone substitute developers and to
      orthopedic surgeons for using bone substitute materials according to their
      mechanical environment.

PMID- 19180635
TI  - Primary tumor thickness as a risk factor for contralateral cervical metastases in
      T1/T2 oral tongue squamous cell carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: Contralateral cervical metastases represent an avoidable
      source of failure in squamous cell carcinoma (SCCa) of the oral tongue. We sought
      to identify risk factors for the development of contralateral cervical metastases
      in T1/T2 oral tongue SCCa. STUDY DESIGN: Retrospective review. METHODS: We
      reviewed the medical records of 50 sequential cases of Stage I/II SCCa of the
      oral tongue treated with surgery between 1983 and 2003 at Loyola University
      Medical Center and Hines VA Hospital. Clinical staging, primary tumor thickness,
      results of neck dissection, adjuvant treatment, site and date of recurrence, and
      final outcome were recorded. Follow-up ranged from 0.2 to 17 years, with a mean
      of 5 years. Data were analyzed using multivariate logistic, Cox regression
      analysis, and a classification and logistic regression tree analysis. RESULTS:
      The odds ratio for risk of developing contralateral neck metastasis was 5% for
      each 1 mm increase in tumor thickness (P = .68). The risk did not change when
      controlling for the presence of ipsilateral metastasis. There was a significant
      relationship between contralateral cervical metastases and the development of
      recurrent disease at any site (P = .005). Classification tree analysis determined
      the risk for contralateral metastases and was greatest for patients with tumors >
      3.75 mm thick and < or = 9.5 mm thick. CONCLUSIONS: This report is the first to
      our knowledge that evaluates thickness as a risk factor for contralateral
      cervical metastasis in oral tongue SCCa. We recommend consideration be given to
      treating the contralateral neck in cases where the primary tumor is > 3.75 mm
      thick.

PMID- 19180636
TI  - Postmastectomy radiotherapy for breast cancer: patterns, correlates,
      communication, and insights into the decision process.
AB  - BACKGROUND: Given accumulating evidence supporting postmastectomy radiotherapy
      (PMRT) in selected patients, it is important to evaluate patterns and correlates
      of PMRT utilization, including communication and attitudinal factors. METHODS:
      The authors surveyed 2382 patients diagnosed with breast cancer in 2002 and
      reported to the Los Angeles and Detroit Surveillance, Epidemiology, and End
      Results registries (n=1844, 77.4% response rate). Analyses were restricted to
      patients with nonmetastatic invasive breast cancer treated by mastectomy who had
      decided whether or not to undergo PMRT (n=396). The authors assessed rates of
      explanation, recommendation, and receipt of radiation by indication grouping,
      defined primarily by the 2001 American Society of Clinical Oncology guidelines.
      They evaluated correlates of PMRT receipt, including tumor and sociodemographic
      characteristics. They also explored patients' self-reported reasons for
      nonreceipt of PMRT. RESULTS: The adjusted proportion in each indication group
      reporting that a provider had explained radiation was high (77% of those in whom
      PMRT was indicated, 76% of those in whom medical opinion was divided, and 73% of
      those in whom PMRT was not indicated; P=.10). The adjusted proportions reporting
      recommendations for radiation (86%, 35%, and 17%, respectively) and receipt (81%,
      34%, and 10%, respectively) varied significantly by indication grouping (P<.001).
      On multivariate analysis, tumor size (P<.001), lymph node status (P<.001),
      comorbidity (P=.02), and chemotherapy receipt (P=.003) were found to be
      independent significant correlates of PMRT receipt. The most common reasons cited
      for not pursuing PMRT were lack of physician recommendation and perceived lack of
      need. CONCLUSIONS: PMRT receipt is strongly correlated with clinical indication.
      The authors found no sociodemographic disparities in utilization. However,
      approximately one-fifth of patients with strong indications did not receive
      treatment.

PMID- 19180637
TI  - A phase 1/pilot study of radiofrequency ablation for the treatment of recurrent
      pediatric solid tumors.
AB  - BACKGROUND: This prospective study was designed to be the first to evaluate the
      toxicity of radiofrequency ablation (RFA) in patients with recurrent pediatric
      solid tumors. METHODS: From 2003 through 2008, a phase 1/pilot study of RFA for
      recurrent pediatric solid tumors was conducted. A multidisciplinary cancer
      management team selected appropriate candidates for the study. Imaging-guided RFA
      was performed percutaneously. Repeat RFA was performed for recurrences when
      appropriate. Toxicity and imaging response was assessed at 1 month and 3 months
      prospectively. Accrual stopped in 2006, and data collection stopped in 2008.
      RESULTS: Sixteen patients (ages 4 years-33 years; median age, 15 years) and 56
      tumor sites were treated in 37 RFA sessions including 38 pulmonary, 11
      musculoskeletal, and 7 hepatic lesions (82 lesion-treatments). Postprocedural
      pain was moderate (median 5 on a scale from 1 to 10) and lasted a median of 9
      days. Prolonged hospitalization (beyond 1 day) occurred 17 times (range, 2 days
      25 days; median, 3 days). Hypoxia supported by supplemental oxygen occurred in 8
      of 16 patients and resolved within 1 month after each RFA. No patient had tumor
      lysis syndrome but myoglobinuria/hemoglobinuria occurred in 6 of 16 patients, all
      without renal damage. Serious complications from pulmonary RFA included 2
      diaphragmatic hernias. Of 82 lesions imaged, 24 (29%) remained ablated at the end
      of the study. CONCLUSIONS: The toxicity from RFA of recurrent pediatric solid
      tumors was real but limited, and RFA may offer a local tumor control alternative
      in carefully selected cases.

PMID- 19180638
TI  - SpOPT1, a member of the oligopeptide family (OPT) of the fission yeast
      Schizosaccharomyces pombe, is involved in the transport of glutathione through
      the outer membrane of the cell.
AB  - A protein involved in the transport of glutathione has been identified, cloned
      and characterized from the fission yeast Schizosaccharomyces pombe. Database
      searches revealed the Sz. pombe ORF SPAC29B12.10c as a close homologue to several
      members of the OPT family, including the Saccharomyces cerevisiae high-affinity
      glutathione transporter Hgt1p. The gene product of SPAC29B12.10c has been
      identified as a protein, named SpOPT1, localized within the plasma membrane,
      transporting the tripeptide glutathione. Disruption of SPAC29B12.10c led to
      strains inable to grow on media containing glutathione as a sole source of
      sulphur, due to the inability to internalize the tripeptide. Disruptants
      contained significantly less glutathione than wild-type cells. Furthermore,
      DeltaSpopt1 strains were non-viable in a glutathione biosynthesis-defective
      (Deltagsh2) background. However, it was possible to complement the disruption of
      Spopt1 by overexpressing the intact ORF in the disrupted strain.

PMID- 19180639
TI  - HIV-1 integrase trafficking in S. cerevisiae: a useful model to dissect the
      microtubule network involvement of viral protein nuclear import.
AB  - Intracellular transport of karyophilic cargos comprises translocation to the
      nuclear envelope and subsequent nuclear import. Small cargos such as isolated
      proteins can reach the nuclear envelope by diffusion but movement of larger
      structures depends on active translocation, typically using microtubules.
      Centripetal transport ends at the perinuclear microtubule organizing centre
      called the spindle pole body (SPB) in yeast. Previously, we found by two hybrids
      that the karyophilic lentiviral-encoded integrase (IN) interacts with two yeast
      microtubule-associated proteins, Dyn2p (dynein light chain protein) and Stu2p, a
      centrosomal protein (de Soultrait et al., 2002). Thus, to investigate the hinge
      between cytoplasmic retrograde transport and nuclear import, we decided to
      analyse HIV-1 IN trafficking in yeast as the model, since each of these
      biological mechanisms is evolutionarily conserved in eukaryotic cells. Here, we
      found an accumulation of IN at the SPB in yeast via Stu2p colocalization.
      Disruption of the microtubule network by nocodazole or IN expression in a dynein
      2-deficient yeast strain prevented IN accumulation in the nuclear periphery and
      additionally inhibited IN transport into the nucleus. By mutagenesis, we showed
      that trafficking of IN towards the SPB requires the C-terminus of the molecule.
      Taking our findings together, we proposed a model in which IN nuclear import
      seems to depend on an essential intermediate step in the SPB. We found that Dyn2p
      and Stu2p play an important role in driving IN toward MTOC and could optimize
      nuclear entry of the retroviral enzyme. Our results suggest a new hypothesis in
      keeping with the current HIV-1 intracellular trafficking model.

PMID- 19180640
TI  - Plasmids with E2 epitope tags: tagging modules for N- and C-terminal PCR-based
      gene targeting in both budding and fission yeast, and inducible expression
      vectors for fission yeast.
AB  - A single-step PCR-based epitope tagging enables fast and efficient gene targeting
      with various epitope tags. This report presents a series of plasmids for the E2
      epitope tagging of proteins in Saccharomyces cerevisiae and Schizosaccharomyces
      pombe. E2Tags are 10-amino acids (epitope E2a: SSTSSDFRDR)- and 12 amino acids
      (epitope E2b: GVSSTSSDFRDR)-long peptides derived from the E2 protein of bovine
      papillomavirus type 1. The modules for C-terminal tagging with E2a and E2b
      epitopes were constructed by the modification of the pYM-series plasmid. The N
      terminal E2a and E2b tagging modules were based on pOM-series plasmid. The pOM
      series plasmids were selected for this study because of their use of the Cre-loxP
      recombination system. The latter enables a marker cassette to be removed after
      integration into the loci of interest and, thereafter, the tagged protein is
      expressed under its endogenous promoter. Specifically for fission yeast, high
      copy pREP plasmids containing the E2a epitope tag as an N-terminal or C-terminal
      tag were constructed. The properties of E2a and E2b epitopes and the sensitivity
      of two anti-E2 monoclonal antibodies (5E11 and 3F12) were tested using several S.
      cerevisiae and Sz. pombe E2-tagged strains.

PMID- 19180641
TI  - PGK1, the gene encoding the glycolitic enzyme phosphoglycerate kinase, acts as a
      multicopy suppressor of apoptotic phenotypes in S. cerevisiae.
AB  - In a previous paper we reported the construction of a S. cerevisiae strain
      lacking the essential gene LSM4, which could survive by the introduction of a
      truncated form of the orthologous gene from Kluyveromyces lactis. This strain
      showed apoptotic hallmarks and other phenotypes, including an increased
      sensitivity to caffeine and acetic acid. The suppression of the latter phenotype
      by overexpressing yeast genes allowed the isolation of PGK1, the gene encoding
      the glycolytic enzyme phosphoglycerate kinase. This gene restored normal ageing,
      oxygen peroxide resistance and nuclear integrity in the mutant. Other phenotypes,
      such as caffeine sensitivity and glycerol utilization, were also suppressed.

PMID- 19180642
TI  - Ubiquitin ligase Rsp5p is involved in the gene expression changes during nutrient
      limitation in Saccharomyces cerevisiae.
AB  - Rsp5p is an essential ubiquitin ligase involved in many different cellular
      events, including amino acid transporters degradation, transcription initiation
      and mRNA export. It plays important role in both stress resistance and adaptation
      to the change of nutrients. We have found that ubiquitination machinery is
      necessary for the correct induction of the stress response SPI1 gene at the entry
      of the stationary phase. SPI1 is a gene whose expression is regulated by the
      nutritional status of the cell and whose deletion causes hypersensitivity to
      various stresses, such as heat shock, alkaline stress and oxidative stress. Its
      regulation is mastered by Rsp5p, as mutations in this gene lead to a lower SPI1
      expression. In this process, Rsp5p is helped by several proteins, such as Rsp5p
      interacting proteins Bul1p/2p, the ubiquitin conjugating protein Ubc1p and
      ubiquitin proteases Ubp4p and Ubp16p. Moreover, a mutation in the RSP5 gene has a
      global effect at the gene expression level when cells enter the stationary phase.
      Rsp5p particularly controls the levels of the ribosomal proteins mRNAs at this
      stage. Rsp5p is also necessary for a correct induction of p-bodies under stress
      conditions, indicating that this protein plays an important role in the post
      transcriptional fate of mRNA under nutrient starvation.

PMID- 19180643
TI  - Effect of trehalose accumulation on response to saline stress in Saccharomyces
      cerevisiae.
AB  - To examine the effect of trehalose accumulation on response to saline stress in
      Saccharomyces cerevisiae, we constructed deletion strains of all combinations of
      the trehalase genes ATH1, NTH1 and NTH2 and examined their growth behaviour and
      intracellular trehalose accumulation under non-stress and saline-stress
      conditions. Saline stress was induced in yeast cells by NaCl addition at the
      exponential growth phase. All deletion strains showed similar specific growth
      rates and trehalose accumulation to their parent strain under non-stress
      conditions. However, under the saline stress condition, one single deletion
      strain, nth1Delta, two double deletion strains, nth1Delta ath1Delta and nth1Delta
      nth2Delta, and the triple deletion strain nth1Deltanth2Delta ath1Delta, all of
      which carry the nth1Delta deletion, showed increased trehalose accumulation as
      compared to the parent and other deletion strains. In particular, our statistical
      analysis revealed that the triple deletion strain showed a higher growth rate
      under the saline stress condition than the parent strain. Moreover, some deletion
      strains showed further trehalose accumulation under non-stress conditions by
      overexpression of the TPS1 or TPS2 genes encoding the enzymes related to
      trehalose biosynthesis at the mid-exponential phase. Such increased trehalose
      accumulation prior to NaCl addition could improve the growth of these strains
      under saline stress. Our results indicate that high trehalose accumulation prior
      to NaCl addition, rather than after NaCl addition, is necessary to achieve high
      growth activity under stress conditions.

PMID- 19180645
TI  - Revival of the biological sunlight-to-biogas energy conversion system.
AB  - In the quest for renewable resources, algae are increasingly receiving attention.
      Their high growth rate, high CO(2) fixation and their lack of requirement for
      fertile soil surface represent several advantages as compared to conventional
      (energy) crops. Through their ability to store large amounts of oils, they
      qualify as a source for biodiesel. Algal biomass, however, can also be used as
      such, namely as a substrate for anaerobic digestion. In the present research, we
      investigated the use of algae for energy generation in a stand-alone, closed-loop
      system. The system encompasses an algal growth unit for biomass production, an
      anaerobic digestion unit to convert the biomass to biogas and a microbial fuel
      cell to polish the effluent of the digester. Nutrients set free during digestion
      can accordingly be returned to the algal growth unit for a sustained algal
      growth. Hence, a system is presented that continuously transforms solar energy
      into energy-rich biogas and electricity. Algal productivities of 24-30 ton VS ha(
      1) year(-1) were reached, while 0.5 N m(3) biogas could be produced kg(-1) algal
      VS. The system described resulted in a power plant with a potential capacity of
      about 9 kW ha(-1) of solar algal panel, with prospects of 23 kW ha(-1).

PMID- 19180644
TI  - Coexpression of alpha 2A-adrenergic and delta-opioid receptors in substance P
      containing terminals in rat dorsal horn.
AB  - Agonists acting at alpha(2)-adrenergic and opioid receptors (alpha(2)ARs and ORs,
      respectively) inhibit pain transmission in the spinal cord. When coadministered,
      agonists activating these receptors interact in a synergistic manner. Although
      the existence of alpha(2)AR/OR synergy has been well characterized, its mechanism
      remains poorly understood. The formation of heterooligomers has been proposed as
      a molecular basis for interactions between neuronal G-protein-coupled receptors.
      The relevance of heterooligomer formation to spinal analgesic synergy requires
      demonstration of the expression of both receptors within the same neuron as well
      as the localization of both receptors in the same neuronal compartment. We used
      immunohistochemistry to investigate the spatial relationship between alpha(2)ARs
      and ORs in the rat spinal cord to determine whether coexpression could be
      demonstrated between these receptors. We observed extensive colocalization
      between alpha(2A)-adrenergic and delta-opioid receptors (DOP) on substance P (SP)
      immunoreactive (-ir) varicosities in the superficial dorsal horn of the spinal
      cord and in peripheral nerve terminals in the skin. alpha(2A)AR- and DOP-ir
      elements were colocalized in subcellular structures of 0.5 mum or less in
      diameter in isolated nerve terminals. Furthermore, coincubation of isolated
      synaptosomes with alpha(2)AR and DOP agonists resulted in a greater-than-additive
      increase in the inhibition of K(+)-stimulated neuropeptide release. These
      findings suggest that coexpression of the synergistic receptor pair alpha(2A)AR
      DOP on primary afferent nociceptive fibers may represent an anatomical substrate
      for analgesic synergy, perhaps as a result of protein-protein interactions such
      as heterooligomerization.

PMID- 19180646
TI  - Neural tube defects in Australia: trends in encephaloceles and other neural tube
      defects before and after promotion of folic acid supplementation and voluntary
      food fortification.
AB  - BACKGROUND: Use of periconceptional folic acid supplementation has been promoted
      in Western Australia since late 1992, and voluntary fortification of some foods
      with folic acid has been permitted in Australia since 1996. Reduced rates of
      neural tube defects (NTDs) have been observed since 1995. Aboriginal infants have
      a higher rate of NTDs, but no fall in rates has been documented. Encephaloceles
      have not been examined separately. METHODS: Data on anencephaly, spina bifida,
      and encephalocele were obtained from the Western Australian Birth Defects
      Registry. The prevalence ratio for each type of NTD was calculated, comparing
      1993 to 1995 (promotion of supplements, no fortification) and 1996 to 2006
      (promotion of supplements and voluntary fortification) with 1980 to 1992 (no
      promotion or fortification). RESULTS: From 1996 to 2006, there was a 32%
      reduction in anencephaly, 23% in spina bifida, and 34% in encephalocele compared
      with 1980 to 1992. There were no differences seen from 1993 to 1995 compared with
      1980 to 1992. For Aboriginal infants, the rates were higher than for non
      Aboriginal infants, for each type of NTD. The prevalence ratios, comparing 1996
      to 2006 with 1980 to 1995, were 0.70 (CI, 0.61-0.79) for non-Aboriginal infants
      and 0.90 (CI, 0.61-1.32) for Aboriginal infants. CONCLUSIONS: Overall, the rates
      of encephalocele, anencephaly, and spina bifida have fallen to a similar extent
      in association with promotion of folic acid supplements and voluntary
      fortification. No such falls were seen for Aboriginal infants. These data will
      provide a useful baseline against which to monitor the effects of mandatory
      fortification on NTDs when it is introduced in Australia in September 2009.

PMID- 19180648
TI  - Effects of maternal hyperthermia on myogenesis-related factors in developing
      upper limb.
AB  - BACKGROUND: Maternal hyperthermia is one causative factor in various congenital
      anomalies in experimental animals and humans. In the present study, we assessed
      the effects of high temperature on limb myogenesis in mice. METHODS: Pregnant
      mice, C57BL/6 strain, were exposed to hyperthermia (43 degrees C, 5 minutes) on
      embryonic day (ED) 8. Fetuses on ED 11, 13, 15, and 17 and neonates on postnatal
      day (PD) 1 were collected. To characterize the effects of hyperthermia on
      myogenesis-related factors Pax3, MyoD, myogenin, and myosin heavy chain (MyHC)
      during skeletal muscle development, we performed RT-PCR, western blotting,
      immunohistochemistry, and transmission electron microscopy. RESULTS: Pax3 gene
      expression was still detected on ED 13 in hyperthermia-exposed fetuses. The
      expression of MyoD protein was down-regulated in fetuses exposed to hyperthermia.
      In contrast, myogenin and MyHC protein expression were up-regulated on PD 1 and
      ED 17, respectively, in the group exposed to hyperthermia. Immunohistochemical
      analysis confirmed the findings from western blot analysis. Compared with control
      neonates, a TEM study revealed immature muscle fibers in PD 1 hyperthermia
      neonates. Thus, our studies showed that maternal hyperthermia induced delayed
      expression of Pax3 and inhibited expression of MyoD proteins, which are known to
      play important roles in migration of myogenic progenitor cells, and in myoblast
      proliferation. In addition, maternal hyperthermia also delayed the expression of
      myogenin protein for the formation of myotubes, and MyHC protein, which is one of
      the final muscle differentiation factors. CONCLUSION: Our data suggest that
      maternal hyperthermia delays limb myogenesis in part by disregulating the
      expression of key myogenesis-related factors.

PMID- 19180647
TI  - Regulation of folate receptor 1 gene expression in the visceral endoderm.
AB  - BACKGROUND: Nutrient supply to the developing mammalian embryo is a fundamental
      requirement. Before completion of the chorioallantoic placenta, the visceral
      endoderm plays a crucial role in nurturing the embryo. We have found that
      visceral endoderm cells express folate receptor 1, a high-affinity receptor for
      the essential micronutrient folic acid, suggesting that the visceral endoderm has
      an important function for folate transport to the embryo. The mechanisms that
      direct expression of FOLR1 in the visceral endoderm are unknown. METHODS:
      Sequences were tested for transcriptional activation capabilities in the visceral
      endoderm utilizing reporter gene assays in a cell model for extraembryonic
      endoderm in vitro, and in transgenic mice in vivo. RESULTS: With F9 embryo
      carcinoma cells as a model for extraembryonic endoderm, we demonstrate that the
      P4 promoter of the human FOLR1 gene is active during differentiation of the cells
      towards visceral endoderm. However, transgenic mouse experiments show that
      promoter sequences alone are insufficient to elicit reporter gene transcription
      in vivo. Using sequence conservation as guide to choose genomic sequences from
      the human FOLR1 gene locus, we demonstrate that the sequence termed F1CE2
      exhibits specific enhancer activity in F9 cells in vitro, in the visceral
      endoderm, and later the yolk sac in transgenic mouse embryos in vivo. We further
      show that the transcription factor HNF4-alpha can activate this enhancer
      sequence. CONCLUSIONS: We have identified a transcriptional enhancer sequence
      from the FOLR1 locus with specific activity in vitro and in vivo, and suggest
      that FOLR1 is a target for regulation by HNF4-alpha.

PMID- 19180649
TI  - Maternal serum homocysteine and risk for neural tube defects in a Texas-Mexico
      border population.
AB  - BACKGROUND: To better understand the neural tube defect (NTD) causal pathway, the
      authors measured homocysteine, an indicator of tissue micronutrient deficiencies.
      The authors examined independent and joint associations of serum homocysteine,
      B12, and folate and red blood cell (RBC) folate with NTD-affected pregnancies.
      METHODS: Case women in this population-based study had NTD-affected pregnancies
      and resided and delivered in one of the 14 Texas-Mexico border counties from 1995
      through 2000. Control women were study area residents delivering normal live
      births during the same period. The authors measured homocysteine levels using
      tandem mass spectroscopy; competitive binding was used for other biomarkers.
      RESULTS: Homocysteine testing was done on 103 cases and 139 controls. Odds ratios
      (ORs) were increased in all upper homocysteine quintiles compared to the lowest
      quintile (1.7, 1.3, 2.8, 2.4). Women with high homocysteine values had increased
      ORs regardless of high versus low levels for B12 (OR = 3.5, 4.8, respectively) or
      RBC folate (OR = 2.9, 3.5, respectively). CONCLUSIONS: High serum homocysteine
      levels are associated with NTD-affected pregnancies. Moreover, high homocysteine
      levels have a detrimental effect on NTD-risk even when serum B12 or RBC folate
      levels are high. Excess homocysteine might play an independent role in the
      development of NTDs.

PMID- 19180650
TI  - Fetal cardiac effects of maternal hyperglycemia during pregnancy.
AB  - Maternal diabetes mellitus is associated with increased teratogenesis, which can
      occur in pregestational type 1 and type 2 diabetes. Cardiac defects and with
      neural tube defects are the most common malformations observed in fetuses of
      pregestational diabetic mothers. The exact mechanism by which diabetes exerts its
      teratogenic effects and induces embryonic malformations is unclear. Whereas the
      sequelae of maternal pregestational diabetes, such as modulating insulin levels,
      altered fat levels, and increased reactive oxygen species, may play a role in
      fetal damage during diabetic pregnancy, hyperglycemia is thought to be the
      primary teratogen, causing particularly adverse effects on cardiovascular
      development. Fetal cardiac defects are associated with raised maternal
      glycosylated hemoglobin levels and are up to five times more likely in infants of
      mothers with pregestational diabetes compared with those without diabetes. The
      resulting anomalies are varied and include transposition of the great arteries,
      mitral and pulmonary atresia, double outlet of the right ventricle, tetralogy of
      Fallot, and fetal cardiomyopathy.A wide variety of rodent models have been used
      to study diabetic teratogenesis. Both genetic and chemically induced models of
      type 1 and 2 diabetes have been used to examine the effects of hyperglycemia on
      fetal development. Factors such as genetic background as well as confounding
      variables such as obesity appear to influence the severity of fetal abnormalities
      in mice. In this review, we will summarize recent data on fetal cardiac effects
      from human pregestational diabetic mothers, as well as the most relevant findings
      in rodent models of diabetic cardiac teratogenesis.

PMID- 19180651
TI  - Zoonotic Ljungan virus associated with central nervous system malformations in
      terminated pregnancy.
AB  - BACKGROUND: The Ljungan virus (LV) has been shown to cause central nervous system
      malformations in laboratory mouse models. The LV has also been associated with
      intrauterine fetal death in humans. We investigated the presence of LV in a
      series of human hydrocephaly and anencephaly cases from elective abortions.
      METHODS: A series of elective abortions owing to hydrocephaly, anencephaly, and
      similarly aged trisomy 21 elective abortions as controls were examined for LV by
      immunohistochemistry and real time RT-PCR. A second experiment involved newborn
      mice exposed to LV. RESULTS: LV was diagnosed in 9 of 10 cases with hydrocephalus
      and in 1 of 18 trisomy 21 controls by immunohistochemistry. Five of nine cases
      with anencephaly had a positive PCR result, whereas none of the 12 trisomy 21
      available for PCR testing had a positive result. The 47 newborn mice exposed to
      LV all developed encephalitis, with eight having hydrocephalus. None of the 52
      control animals had encephalitis or hydrocephalus. CONCLUSION: The association
      between LV and both hydrocephaly and anencephaly suggests that LV may be playing
      an important role in central nervous system malformations in humans.

PMID- 19180652
TI  - Time dependent vascular and myocardial responses of a second generation, small
      vessel, paclitaxel-eluting stent platform.
AB  - OBJECTIVES: The purpose of this study was to evaluate the time-dependent vascular
      and myocardial responses to a second-generation, small vessel (< or =2.5 mm)
      paclitaxel-eluting stent (PES) platform. BACKGROUND: Small caliber coronary
      vessels present complex challenges for percutaneous coronary intervention (PCI)
      and are associated with lower technical success and inferior long-term efficacy.
      A next-generation, highly deliverable PES may improve clinical outcomes in small
      vessels. METHODS: Sixty single stents were implanted in noninjured coronary
      arteries in 30 domestic swine (one TAXUS Liberte small vessel PES (svPES) and one
      Liberte small vessel bare metal stent (svBMS) in each animal). Ten animals each
      were allocated to 30-, 90-, and 180-day follow-up groups; final quantitative
      angiography and necropsy were performed. Samples of myocardium, liver, and kidney
      were processed and evaluated for pathology. Radiography and either histopathology
      or scanning electron microscopy were performed on all the explanted stented
      vessels. RESULTS: There were no stent-related deaths or downstream myocardial
      pathology. Both the svPES stent and its svBMS control demonstrated complete strut
      tissue coverage and complete endothelialization at all timepoints, and there was
      no evidence of macro- or microscopic thrombus or stent fracture. Medial smooth
      muscle cell content was markedly reduced in all the svPES groups compared with
      that in the svBMS controls. CONCLUSIONS: The small diameter paclitaxel-eluting
      TAXUS Liberte stent has a safe and predictable biologic vascular response in the
      noninjured swine model. This device warrants further investigation targeting the
      currently poorly met clinical need for small vessel PCI.

PMID- 19180653
TI  - Combined percutaneous revascularization and cell therapy after failed repair of
      anomalous origin of left coronary artery from pulmonary artery.
AB  - This report shows the course of an infant with an abnormal left coronary artery
      origin arising from the pulmonary artery who underwent failed surgical
      reimplantation. Treatment entailed combined stent revascularization followed by
      intracoronary infusion of bone marrow-derived mononuclear cells. The patient was
      admitted with an acute coronary syndrome and low cardiac output; he was
      endotracheally intubated under respiratory assistance. Fourteen months after
      intracoronary infusion of autologous bone marrow-derived mononuclear cells, the
      infant remains symptom-free with significant recovery of the left ventricular
      function. These findings suggest that the combination of percutaneous
      revascularization and cell therapy should be considered in those infants or
      children in whom salvage therapy for ischemic heart disease is required.

PMID- 19180654
TI  - Arterial complications associated with cardiac catheterization in pediatric
      patients with a previous history of Kawasaki disease.
AB  - OBJECTIVES: To determine whether patients with Kawasaki Disease (KD) undergoing
      percutaneous catheter angiography were at increased risk of arterial
      complications at the point of arterial access compared to patients with
      structural heart abnormalities, but normal vessels. BACKGROUND: Systemic arterial
      damage can occur as a result of KD. METHODS: Medical histories of all patients
      with KD undergoing percutaneous catheter angiography at The Hospital for Sick
      Children between January 1990 and August 2008 were reviewed. RESULTS: A total of
      44 patients with KD underwent 82 catheter procedures. Of these, 3 were associated
      with important arterial complications (2 males; age: 4 months, 3 and 17 years).
      All patients who experienced complications had multiple large and/or giant
      coronary artery aneurysms and two were within 3 months of the acute phase of KD.
      All patients developed pseudoaneurysms of the femoral artery which had been
      utilized for catheter access. All pseudoaneurysms were treated with ultrasound
      guided thrombin injection and compression, and resolved with no long-term
      complications. One patient also developed a substantial arteriovenous fistula of
      the femoral circulation which had to be surgically repaired with no permanent
      sequela. Odds for arterial complications in patients with KD were 10.4 times
      greater (95%CI: 3.2-33.8) than that noted for the general pediatric cardiac
      catheterization population (3.6% vs. 0.4%, P < 0.0001) which indicates higher
      risk associated with arterial access in patients with KD. CONCLUSIONS: Greater
      care in obtaining arterial access for angiography is warranted, especially in the
      first month directly following the acute phase, possibly related to systemic
      arterial damage associated with KD.

PMID- 19180655
TI  - Aspiration of embolized thrombus during primary percutaneous coronary
      intervention.
AB  - During percutaneous coronary intervention for acute myocardial infarction, distal
      embolization of thrombus and plaque material often occurs, despite the use of
      thrombectomy and aspiration catheters. Large embolized thrombi can cause
      occlusion of distal coronary vessels for which angioplasty most often leads to no
      more than poor results. We describe the successful use of an aspiration catheter
      to treat distally embolized thrombus, to optimize coronary reperfusion therapy,
      and to improve salvage of myocardial tissue. We discuss the manifestation and
      incidence of distal embolization and show its clinical relevance.

PMID- 19180656
TI  - The valve-in-valve technique: transcatheter treatment of aortic bioprothesis
      malposition.
AB  - Percutaneous aortic valve replacement is an emerging alternative to palliative
      medical therapy for nonsurgical patients with severe aortic valve stenosis. The
      impossibility of repositioning of the current transcatheter prosthesis in case of
      suboptimal placement is the main limit of these devices. Here, we report on a
      case of an 84-year-old woman successfully treated with implantation of two 18-Fr
      CoreValve prosthesis (CoreValve, Irvine, California), because of the suboptimal
      deployment of the first one, analyzing the procedural technique and the immediate
      and short-term clinical and hemodynamic results.

PMID- 19180657
TI  - Catheter-based treatment with the Amplatzer devices in alien positions.
AB  - OBJECTIVE: Case reports of patients with Amplatzer devices used in positions they
      have not been designed for have repeatedly been published. BACKGROUND: We pooled
      our results to review the array of such interventions. METHODS: Retrospective
      study of twelve patients presented with eleven different problems: Two patients
      had hepatoatrial communication after Fontan's operation, two had different types
      of fistulae, two had surgical shunts, two had different anomalous systemic venous
      drainage, and two had an open arterial duct, one huge and hypertensive, the other
      with a very shallow ampulla. Finally, in one, a pulmonary artery was closed as a
      preparation for a bidirectional cavo-pulmonary anastomosis. RESULTS: All
      communications were completely closed. As only complication a lesion of the
      anonymous vein causing haematothorax was noted when trying to access through a
      Gore-Tex membrane after puncture. CONCLUSIONS: Such applications of Amplatzer
      devices in alien positions are estimated to be needed in 1 in 5-700
      catheterizations. The results are good and the complications few.

PMID- 19180658
TI  - Fracture of a GORE HELEX septal occluder following PFO closure in a diver.
AB  - Decompression illness (DCI) is more common in divers with a patent foramen ovale
      (PFO), and transcatheter PFO closure is being increasingly performed in patients
      with an episode of DCI who want to continue diving. A range of closure devices
      are available and the choice in an individual case depends on operator preference
      and PFO anatomy. The GORE HELEX Septal Occluder, introduced in 1999 primarily for
      secundum atrial defect closure, is a compliant non self-centering device composed
      of a wire helical framework on which a microporous membrane is mounted. The
      device is fixed in place by a unique interlocking mechanism that passes through
      the center of the device from the left to the right atrial disc, thereby securing
      it onto the interatrial septum. Here, we present a case of a locking loop
      fracture and review the literature concerning this unusual complication.

PMID- 19180659
TI  - Complication rate of diagnostic carotid angiography performed by interventional
      cardiologists.
AB  - OBJECTIVE: The aim of this study was to evaluate the complication rate of
      diagnostic carotid angiography performed by interventional cardiologists and
      compare it to previously published data. BACKGROUND: Percutaneous treatment for
      carotid artery stenosis is increasingly being performed. Previously published
      data describes the complication rate of diagnostic carotid angiography performed
      by radiologists and vascular surgeons, yet the information regarding
      interventional cardiologists is sparse. Currently in the United States,
      interventional cardiologists perform a great deal of diagnostic carotid
      angiograms. METHODS: A retrospective analysis was done on 333 patients who
      underwent diagnostic carotid angiography at a single medical center from January
      2000 to February 2007. Medical records were reviewed for cardiovascular risk
      factors, indications for the procedure, angiography technique and in-hospital
      complications. Complications were categorized as neurological and non
      neurological. Neurological complications were further grouped into transient (<7
      days) or permanent. Non-neurological complications were grouped into major
      (requiring additional treatment) or minor. RESULTS: Three hundred and thirty
      three patients underwent 347 diagnostic carotid angiograms. Twelve (3.5%)
      complications occurred in 12 patients. No cerebral vascular accidents occurred
      and only one (0.3%) transient ischemic attack occurred. Two patients required
      blood transfusions following the index procedure yielding a major non
      neurological complication rate of 0.6%. Review of the literature revealed a
      transient neurological complication rate from 0 to 2.4% and a major non
      neurological complication rate of 0.26-4.3%. CONCLUSIONS: Neurological and non
      neurological complication rates for carotid angiograms performed by
      interventional cardiologists are low and compare well with the literature.
      Interventional cardiologists can safely perform diagnostic carotid angiography
      with low complication rates.

PMID- 19180660
TI  - The bifurcation study using 64 multislice computed tomography.
AB  - BACKGROUND: Various two-stent techniques have been applied to aggressively treat
      bifurcation lesions as the introduction of drug-eluting stents (DES) and the
      importance of the bifurcation angle and three-dimensional (3D) structure has come
      to be recognized. Recent 64 multislice computed tomography (MSCT) technology
      provides accurate information about the 3D bifurcation geometry of the coronary
      arteries and with reproducibility. OBJECTIVES: The purpose of this study is to
      disclose the coronary bifurcation angle and 3D structure in humans and elucidate
      the importance of bifurcation angle for the crush technique using MSCT. METHODS:
      Two hundred and nine patients who were suspected to have angina pectoris and
      underwent CT angiography using MSCT were examined. The 3D-volume rendering (VR)
      image was reconstructed by two technicians and was used for the assessment of
      each coronary bifurcation angles. RESULTS: The average LMT bifurcation angles
      (angle LMT-LAD, angle LMT-LCx, angle LAD-LCx) were 143 +/- 13 degrees , 121 +/-
      21 degrees , and 72 +/- 22 degrees , respectively, the average angle LAD-D was
      138 +/- 19 degrees , the average angle LCx-OM was 134 +/- 23 degrees , the
      average distal RCA bifurcation angles (angle RCA-4AV, angle RCA-4PD, angle 4AV
      4PD) were 152 +/- 15 degrees , 137 +/- 20 degrees , and 61 +/- 21 degrees ,
      respectively. In addition, a percentage of steep angled bifurcation (<110 degrees
      ) was significantly higher in the LMT (26%) than in other bifurcations (P <
      0.05). CONCLUSIONS: LMT bifurcation has been shown to have a higher rate of steep
      angled bifurcation in humans, it is therefore necessary to take the bifurcation
      angle into consideration in the case of LMT stenting. These data suggest that a
      bifurcation study using MSCT can clarify the 3D structure of coronary bifurcation
      and may provide useful information for bifurcation stenting.

PMID- 19180661
TI  - Rotational vs. standard coronary angiography: an image content analysis.
AB  - OBJECTIVE: To evaluate the clinical utility of images acquired from rotational
      coronary angiographic (RA) acquisitions compared to standard "fixed" coronary
      angiography (SA). BACKGROUND: RA is a novel angiographic modality that has been
      enabled by new gantry systems that allow calibrated automatic angiographic
      rotations and has been shown to reduce radiation and contrast exposure compared
      to SA. RA provides a dynamic multiple-angle perspective of the coronaries during
      a single contrast injection. METHODS: The screening adequacy, lesion assessment,
      and a quantitative coronary analysis (QCA) of both SA and RA were compared by
      independent blinded review in 100 patients with coronary artery disease (CAD).
      RESULTS: SA and RA recognize a similar total number of lesions (P = 0.61). The
      qualitative assessment of lesion characteristics and severity between modalities
      was comparable and lead to similar clinical decisions. Visualization of several
      vessel segments (diagonal, distal RCA, postero-lateral branches and posterior
      descending) was superior with RA when compared to SA (P < 0.05). A QCA comparison
      (MLD, MLA, LL, % DS) revealed no difference between SA and RA. The volume of
      contrast (23.5 +/- 3.1 mL vs. 39.4 +/- 4.1; P = 0.0001), total radiation exposure
      (27.1 +/- 4 vs. 32.1 +/- 3.8 Gycm(2); P = 0.002) and image acquisition time (54.3
      +/- 36.8 vs. 77.67 +/- 49.64 sec; P = 0.003) all favored RA. CONCLUSION: Coronary
      lesion assessment, coronary screening adequacy, and QCA evaluations are
      comparable in SA and RA acquisition modalities in the diagnosis of CAD however RA
      decreases contrast volume, image acquisition time, and radiation exposure.

PMID- 19180662
TI  - Outcomes of emergent cardiac catheterization following pediatric cardiac surgery.
AB  - BACKGROUND: Although there is agreement of the importance of cardiac
      catheterization, especially interventional procedures, cardiac catheterization in
      postoperative critical care unit (CCU) period is often debated. The focus of this
      study was to explore the indications for and determinants of outcome after
      cardiac catheterization in this setting. METHODS: Between March 2004 and October
      2006, 49 children (2.8% of cardiac surgeries) underwent 62 catheterizations
      before discharge from the CCU. Morphological, surgical, and catheterization data
      were accrued and analyzed using parametric competing risks models and
      multivariable risk-hazard analysis. RESULTS: Median age at surgery was 167 days
      (0-13.5 years) and time to catheterization was 8.5 (0-84) days following surgery.
      Catheterization procedures were either interventional (n = 35) or
      noninterventional (n = 27). Children who required a more urgent investigation
      following initial surgery more often had deployment of a stent at catheterization
      (P = 0.01) or subsequent surgical pulmonary artery augmentation (P < 0.01).
      Surgical reoperation was required following 23 (37%) catheterizations and was
      more common following index surgery involving a cavopulmonary shunt. Overall
      mortality was high (43%). Delayed invasive investigation beyond 2-3 weeks (P =
      0.04) or a splinted sternum (P < 0.001) were risk factors for death. In addition,
      reoperation after a noninterventional catheterization predicted worse survival (P
      < 0.001). CONCLUSIONS: The need for invasive investigation in the immediate CCU
      period is associated with a poor outcome, especially when the investigation is
      delayed or an intervention is not possible. Identification of at-risk patients
      may improve outcomes. Best outcomes follow expedient catheterization with
      definitive management (often stent deployment or pulmonary artery augmentation).

PMID- 19180663
TI  - Percutaneous closure of patent foramen ovale for migraine headaches refractory to
      medical treatment.
AB  - BACKGROUND: Patent foramen ovale (PFO) has been linked to migraine, and several
      retrospective studies reported an improvement in migraine prevalence or frequency
      after PFO closure for other reasons, mostly for secondary prevention of
      paradoxical embolism or following diving accidents. We investigated the outcome
      of patients undergoing PFO closure solely for migraine headaches refractory to
      medical treatment. METHODS: Seventeen patients (age 44 +/- 12 years; 76% female;
      one atrial septal aneurysm) underwent percutaneous PFO closure using the
      Amplatzer PFO Occluder (AGA Medical Corporation, Golden Valley, MN). An 18-mm
      device was used in two patients, a 25-mm device in 13, and a 35-mm device in two.
      The interventions were solely guided by fluoroscopy, without intraprocedural
      echocardiography. RESULTS: All implantation procedures were successful. There
      were no peri-procedural complications. Contrast transesophageal echocardiography
      after Valsalva maneuver at 6 months showed complete PFO closure in 16 patients
      (94%), whereas a minimal residual shunt persisted in one (6%). During 2.7 +/- 1.5
      years of follow-up, no deaths and no embolic events occurred. After PFO closure,
      migraine headaches disappeared in four patients (24%), and improved in eight
      additional patients (47%). Three patients (18%) reported a decrease of their
      headaches by 75%, three patients (18%) a decrease of 50%, and two patients (12%)
      a decrease of 25%, while headaches remained unchanged in five patients (29%). No
      patient experienced worsening headaches. Moreover, the prevalence of migraine
      with aura decreased from 82 to 24% (P = 0.002). CONCLUSIONS: These results
      suggest that percutaneous PFO closure durably alters the spontaneous course of
      shunt associated migraine.

PMID- 19180664
TI  - Covered Cheatham-Platinum stents for serial dilation of severe native aortic
      coarctation.
AB  - OBJECTIVES: To report on the early results of treatment of native coarctation of
      the aorta by implantation and serial dilations of covered stents. BACKGROUND:
      Transcatheter dilation of native coarctation of the aorta carries a risk of
      aneurysm or rupture. Covered stent implantation requires a large delivery system
      with the risk of vascular damage. METHODS: Covered stents on balloons of diameter
      sufficient to anchor the stent in the coarctation were implanted using the
      smallest delivery system possible. Dilation with larger diameter balloons was
      performed until the pressure gradient was <20 mm Hg and the stent was opposed to
      the aortic wall. RESULTS: Twenty-two patients with native coarctation underwent
      stent implantation. Coarctation diameter increased from 3.6 +/- 1.9 to 12.6 +/-
      1.9 mm (P < 0.001). Peak pressure gradient decreased from 29.4 +/- 8.5 to 6.7 +/-
      5.7 mm Hg (P < 0.001). Nine patients underwent further dilation on average 5
      months later. Residual pressure gradient decreased from 12.3 +/- 5.8 to 2.1 +/-
      2.9 mm Hg (P = 0.002). The stent achieved the diameter of the transverse arch in
      all cases. Complications included a small tear at further dilation treated with a
      second stent and a femoral pseudoaneurysm. At short-term follow-up of 18.5 months
      all patients are alive and well with no evidence of recoarctation or aneurysm.
      CONCLUSIONS: These initial results show that serial dilation of covered Cheatham
      Platinum stents is feasible, safe, and an effective percutaneous method for the
      treatment of native coarctation of the aorta. However, long-term follow up is
      required.

PMID- 19180665
TI  - Multivessel drug-eluting stenting and impact of diabetes mellitus--a report from
      the EVENT registry.
AB  - OBJECTIVES: To compare clinical outcomes in patients with and without diabetes
      after multivessel percutaneous coronary intervention (PCI). BACKGROUND: Diabetes
      is associated with significantly worse outcomes after multivessel PCI and
      coronary bypass surgery is recommended as the preferred option for these
      patients. METHODS AND RESULTS: The Evaluation of Drug Eluting Stents and Ischemic
      Events registry is a multicenter evaluation of acute and 1 year outcomes in
      unselected patients undergoing PCI since approval of drug-eluting stents (DES).
      Major adverse cardiac events (MACE) were defined as all cause mortality,
      myocardial infarction, or repeat revascularization and rate was estimated by
      Kaplan-Meier method and compared using log-rank. The independent correlates of
      MACE were determined using Cox proportional hazards regression. Of 4,819
      nonemergency native coronary DES procedures, 1,595 (33.1%) were in patients with
      diabetes and 722 (11.7%) involved >1 vessel. Of patients undergoing multivessel
      procedures, diabetes was present in 256 (35.5%). One year after multivessel PCI,
      MACE was similar for patients with or without diabetes (22.3% versus 21.2%, log
      rank test P = 0.85). The independent correlates of 1 year MACE were female sex
      (Hazard ratio [HR], 1.58, 95% CI 1.14-2.20), ejection fraction (HR 0.74 per group
      [<25%, 26-35%, 36-50%, and >50%], 95%CI 0.59-0.94) and number of stents (HR 1.20
      per stent, 95%CI 1.04-1.38) but not diabetes (HR 1.00, 95% CI 0.71-1.39).
      CONCLUSIONS: Multivessel DES is performed commonly in patients with diabetes with
      outcomes at 1 year similar to patients without diabetes. Longer follow-up is
      required to more fully evaluate the safety and effectiveness of this strategy.

PMID- 19180667
TI  - Gamma-linolenic acid alters Ku80, E2F1, and bax expression and induces
      micronucleus formation in C6 glioma cells in vitro.
AB  - Gamma-linolenic acid (GLA) is an inhibitor of tumor cell proliferation in both in
      vitro and in vivo conditions. The aim of this study was to investigate the
      effects of 150 muM GLA on the expression of E2F1, cyclin D1, bax, bcl2, Ku70, and
      Ku80 in C6 rat glioma cells. The Ku proteins were chosen as previous studies have
      shown that loss or reduction in their expression causes increased DNA damage and
      micronucleus formation in the presence of radiation. The fact that GLA exposure
      is known to enhance the efficacy of radiation treatment raised the question
      whether the Ku proteins could be involved in this effect as seen for other
      molecules such as roscovitine and flavopiridol. GLA altered the mRNA expression
      of E2F1, cyclin D1, and bax, but no changes were found for bcl2, Ku70, and Ku80.
      Alterations in protein expression were observed for bax, Ku80, and E2F1. The 45%
      decrease in E2F1 expression was proportional to decreased cell proliferation
      (44%). Morphological analysis found a 25% decrease in mitotic activity in the GLA
      treated cells, which was accompanied by a 49% decrease in S-phase by FACS
      analysis. A 39% increase in the number of micronuclei detected by Hoechst
      fluorescence points to GLA's effects on cell division even at concentrations that
      do not produce significant increases in apoptosis. Most important was the finding
      that Ku80 expression, a critical protein involved in DNA repair as a heterodimer
      with Ku70, was decreased by 71%. It is probable that reduced Ku80 is responsible
      for the increase in micronucleus formation in GLA-treated cells in a similar
      manner to that found in Ku80 null cells exposed to radiation. The decreased
      expression of Ku80 and E2F1 could make cells more susceptible to radiotherapy and
      chemotherapy.

PMID- 19180668
TI  - Directed evolution of enzymes: Library screening strategies.
AB  - Directed evolution has become the preferred engineering approach to generate
      tailor-made enzymes. The method follows the design guidelines of nature:
      Darwinian selection of genetic variants. This review discusses the different
      stages of directed evolution experiments with the focus on developments in
      screening and selection procedures.

PMID- 19180666
TI  - Serine proteases.
AB  - Over one third of all known proteolytic enzymes are serine proteases. Among
      these, the trypsins underwent the most predominant genetic expansion yielding the
      enzymes responsible for digestion, blood coagulation, fibrinolysis, development,
      fertilization, apoptosis, and immunity. The success of this expansion resides in
      a highly efficient fold that couples catalysis and regulatory interactions. Added
      complexity comes from the recent observation of a significant conformational
      plasticity of the trypsin fold. A new paradigm emerges where two forms of the
      protease, E* and E, are in allosteric equilibrium and determine biological
      activity and specificity.

PMID- 19180669
TI  - Extracellular ATP induces retinal photoreceptor apoptosis through activation of
      purinoceptors in rodents.
AB  - We have previously demonstrated that photoreceptors express P2X(7) purinoceptors.
      These excitatory receptors are activated by extracellular adenosine 5'
      triphosphate (ATP) and have been implicated in neurodegeneration in other parts
      of the central nervous system (CNS). In this study we examined whether
      extracellular ATP could contribute to photoreceptor degeneration in rodents
      through excessive activation of P2 purinoceptors. Intravitreal injection of high
      concentrations of extracellular ATP into normal rat eyes induced extensive and
      selective apoptosis of photoreceptors within 18 hours of injection. Five days
      after injection the outer nuclear layer was severely degenerated and
      electroretinographic responses were impaired. Preinjection of the purinergic
      antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS)
      protected against ATP-mediated apoptosis. The initial phase of ATP-induced
      photoreceptor death did not temporally coincide with retinal pigment epithelium
      degeneration or microglial activation, suggesting that cell death was due to
      direct activation of purinergic receptors on photoreceptors. Finally, we
      demonstrate that intravitreal injection of PPADS results in a 30% increase in
      photoreceptor survival in the rd1 mouse, a model of human recessive retinitis
      pigmentosa (RP). These findings highlight the importance of extracellular ATP in
      retinal neurodegeneration and provide a potential new avenue for therapeutic
      intervention in RP.

PMID- 19180670
TI  - I've read that people with kidney disease often do not receive the proper
      medications after a heart attack. Are there heart medications I should avoid if I
      have kidney disease?

PMID- 19180671
TI  - Would you recommend drinking green tea for its supposed health benefits?

PMID- 19180672
TI  - Lifestyle factors for longer life.

PMID- 19180673
TI  - Hot drinks for two kinds of warmth.

PMID- 19180674
TI  - Entry of substances into perilymph through the bone of the otic capsule after
      intratympanic applications in guinea pigs: implications for local drug delivery
      in humans.
AB  - HYPOTHESIS: Drugs applied to the middle ear enter perilymph through the bony otic
      capsule. BACKGROUND: Drugs applied intratympanically in humans are thought to
      enter the cochlea primarily through the round window membrane (RWM). Local drug
      treatments of the ear are commonly evaluated in rodent models. The otic capsule
      is much thinner at the cochlear apex in rodents than in humans. We therefore
      investigated whether drugs applied to the middle ear could enter perilymph
      through the otic capsule as well as through the RWM. METHODS: The distribution of
      gentamicin and the marker trimethylphenylammonium (TMPA) along the guinea pig
      cochlea was assessed with sequential apical perilymph sampling after 2 delivery
      paradigms that included 1) completely filling the tympanic bulla with solution
      and 2) applying the solution to the RWM only. In addition, TMPA entry into
      perilymph of the third turn was measured with ion-selective electrodes after the
      bulla was filled with TMPA solution. RESULTS: In application protocols that
      allowed drug to contact the otic capsule (by completely filling the bulla),
      markedly higher drug concentrations were found in the apical, low-frequency
      regions of the cochlea compared with drug applications to the RWM only.
      CONCLUSION: Gentamicin and TMPA can enter perilymph of guinea pigs through the
      RWM and simultaneously through the bony otic capsule. Drug distribution along the
      cochlea after intratympanic applications will therefore be dramatically different
      in rodents and humans. Results obtained from intratympanic drug treatments of
      animals, in which the bulla is filled with solution and contacts the bony capsule
      of the cochlea, do not provide a good model for the situation in humans.

PMID- 19180675
TI  - Hearing-in-noise benefits after bilateral simultaneous cochlear implantation
      continue to improve 4 years after implantation.
AB  - OBJECTIVE: The purpose of this 4-year longitudinal study was to assess the
      stability of the binaural benefits of head shadow, summation, and squelch for
      bilateral cochlear implant recipients and to quantify these benefits for the
      understanding of speech in noise. DESIGN: This is a prospective study of 9
      patients who received simultaneous bilateral insertion of MED-EL COMBI +40
      cochlear implants in a single-stage operation at the University of North
      Carolina, Chapel Hill, NC. Each patient had postlingual deafness of short
      duration before insertion of the device. Each year, the patients were tested for
      word recognition using consonant-nucleus-consonant words in quiet and speech
      perception in noise using City University of New York sentences. These tests were
      administered using direct audio input to the implants. Head-related transfer
      functions were used to simulate speech in noise testing in a spatial environment.
      Speech was always presented at midline (0 degrees), and the noise masker was
      presented at either side or midline (-90, 0, +90 degrees). RESULTS: The binaural
      benefits of head shadow and summation effects developed early in the
      postoperative period and remained stable throughout the follow-up period. Squelch
      developed more slowly and was first demonstrated at 12 months after implantation
      but continued to increase beyond the first year of follow-up. CONCLUSION:
      Benefits of head shadow and summation emerge early and remain stable. However,
      squelch has the most protracted period of development, with increasing benefit
      after a year or more of implant experience. These data support the idea that
      binaural integration continues several years after insertion of bilateral
      cochlear implant devices.

PMID- 19180676
TI  - Incomplete electrode extraction during cochlear implant revision.
AB  - OBJECTIVES: To report 3 occurrences of incomplete electrode extraction during
      cochlear implant revision, resulting in partial intracochlear retention of an
      implant electrode array. STUDY DESIGN: Retrospective case series. SETTING: Three
      tertiary care academic medical centers. PATIENTS: Three patients with cochlear
      implant failure necessitating revision cochlear implantation. INTERVENTION:
      Diagnosis and surgical revision of failed cochlear implants. RESULTS: A rare
      intraoperative complication was encountered in 3 pediatric patients undergoing
      revision cochlear implantation. During attempted explantation of the indwelling
      electrode, the array fractured and resulted in intracochlear retention of a
      distal portion of the electrode. Each case was managed differently by the
      operative team. CONCLUSION: Incomplete electrode extraction is a rare but
      significant complication of revision cochlear implantation that is generally not
      anticipated when counseling patients and families. Preoperative discussion of
      this potential complication is appropriate.

PMID- 19180677
TI  - Surgery of idiopathic malleus fixation.
AB  - OBJECTIVE: To describe and compare 2 different surgical techniques used in
      treatment of malleus fixation syndrome. STUDY DESIGN: A retrospective study
      including 24 patients (25 ears). In 11 of them, the attical fixation was removed
      via a transmastoid approach without disruption of the ossicular chain. In 14
      patients, an ossiculoplasty was performed via a transcanal approach; the malleus
      head was removed with the incus, and the ossicular chain was reconstructed either
      by incus interposition (9 cases) or by using a partial ossicular replacement
      prosthesis (5 cases). The hearing results were analyzed according to the
      Committee on Hearing and Equilibrium Guidelines of the American Academy of
      Otolaryngology. RESULTS: In the group of attical fixation removed via a
      transmastoid approach, the preoperative air-bone gap (ABG) attained 25.2 dB, and
      the postoperative ABG at 1 year followup was 9.1 dB. In the group of
      ossiculoplasty, the average preoperative ABG reached 26.5 dB, and the
      postoperative ABG at 1-year follow-up was 8.2 dB. CONCLUSION: There was no
      statistically significant difference (p = 0.79) between the 2 surgical techniques
      used to improve hearing in malleus head fixation.

PMID- 19180678
TI  - Coupling the Vibrant Soundbridge to cochlea round window: auditory results in
      patients with mixed hearing loss.
AB  - OBJECTIVE: To assess the functional results of the Vibrant Soundbridge (VBS)
      placed on the round window (RW) in patients with mixed hearing loss. STUDY
      DESIGN: Retrospective evaluation of functional hearing, with measurements
      performed 7 to 9 months postoperatively. SETTINGS: Two tertiary referral hospital
      centers. SUBJECTS: Twelve individuals with mixed severe hearing loss associated
      with chronic suppurative otitis media and otosclerosis. INTERVENTION: Surgical
      placement of the VBS mechanical effector in close contact with the RW membrane to
      directly drive the inner ear fluids. MAIN OUTCOME MEASUREMENT: Functional hearing
      gain as analyzed via pure-tone audiometry and speech audiometry with VBS off and
      on in quiet and in noise. RESULTS: We observed a mean gain of 37.5 dB (0.5-4 kHz)
      with wide individual differences. The overall gain is mainly due to the air-bone
      gap recovery, whereas a further 12-dB mean improvement of air-conducted threshold
      is evident at 2 kHz. The speech reception threshold in quiet shows a mean gain of
      24 dB, whereas in noise, it requires a signal-to-noise ratio 7 to 13 dB greater
      than normal-hearing controls. All patients are daily users of their VBS device.
      CONCLUSION: A middle ear implant capable of directly driving the cochlear fluids
      seems to be a promising alternative for individuals with a severe to profound
      mixed hearing loss. However, variability in hearing recovery is great, likely
      reflecting variability in responsiveness of the cochlea associated with chronic
      pathologic findings and, possibly, variability in how the VBS effector interfaces
      with the RW. Modifying the shape of the VBS effector can improve the mechanical
      coupling to the RW to better exploit the device's amplification power.

PMID- 19180679
TI  - Incidence of horizontal canal benign paroxysmal positional vertigo as a function
      of the duration of symptoms.
AB  - OBJECTIVES: The incidence of horizontal canal involvement in benign paroxysmal
      positional vertigo (HC-BPPV) varies between reports. One of the reasons for these
      differences is that the duration of symptoms was not considered. Because of the
      high spontaneous resolution rate in HC-BPPV and the medical referral system, the
      frequency of HC-BPPV might change according to the duration of symptoms. We
      evaluated the frequency of involved canals in BPPV according to the duration of
      symptoms. STUDY DESIGN: A retrospective review. METHODS: A retrospective review
      was conducted involving 589 patients diagnosed with BPPV from January 2001 to
      December 2006. The patients were divided into 3 groups according to the duration
      of symptoms: Group A included patients who sought evaluation in the clinics
      within 24 hours from the onset of symptoms (n = 328); Group B was composed of
      patients who experienced symptoms from 24 hours to 7 days (n = 87) before
      evaluation; and Group C patients had symptoms for more than 7 days (n = 174)
      before evaluation. The frequencies of involved canals were assessed and compared
      between the groups. The correlation between the frequency of involved canals and
      symptom duration was also analyzed. RESULTS: The posterior, horizontal, and
      anterior canals were involved in 61.8, 35.3, and 2.9% of the patients,
      respectively. However, the frequency of HC-BPPV was 40.5% in Group A, 33.3% in
      Group B, and 26.4% in Group C (p < 0.01). There was a significant negative
      correlation between the frequency of HC-BPPV and the duration of symptoms (r =
      0.670; p < 0.01). CONCLUSION: The incidence of HC-BPPV was higher than reported;
      however, it significantly decreased according to the duration of symptoms.

PMID- 19180680
TI  - Tissue Viability Society business.

PMID- 19180681
TI  - Re: Practice parameter: assessing patients in a neurology practice for risk of
      falls (an evidence-based review): report of the Quality Standards Subcommittee of
      the American Academy of Neurology.

PMID- 19180682
TI  - Re: A randomized, placebo-controlled trial of repeated IV antibiotic therapy for
      Lyme encephalopathy. Prolonged Lyme disease treatment: enough is enough.

PMID- 19180683
TI  - Re: A randomized, placebo-controlled trial of repeated IV antibiotic therapy for
      Lyme encephalopathy. Prolonged Lyme disease treatment: enough is enough.

PMID- 19180686
TI  - From darkening urine to early diagnosis of alkaptonuria.
AB  - Alkaptonuria is a rare disorder of metabolism characterized by deficiency of
      homogentisic acid oxidase. Characteristic features include darkening of urine,
      ochronosis, and arthropathy. Darkening of urine is the only sign of the disorder
      in the pediatric age group, and it occurs at very early stage of the disorder, as
      reported by the parents. A 4-year-old boy presented to our clinic with the
      complaint of dark urine and bluish black staining of clothes. This darkening
      pointed to a positive physical history of bluish discoloration of sclerae which
      occurred off and on. We initiated treatment with ascorbic acid and a protein diet
      with restriction of phenylalanine and tyrosine (1.6 g/kg/d). This case report is
      significant because of the early diagnosis made.

PMID- 19180687
TI  - Scrofuloderma: a clinicopathological and  epidemiological study.

PMID- 19180688
TI  - Hairy plaque on the thigh. Diagnosis: congenital smooth muscle hamartoma.

PMID- 19180690
TI  - [Let's take better care of our reputation--that is possible].

PMID- 19180691
TI  - [Interpretation of Cochrane-reviews].

PMID- 19180692
TI  - [Cognitive deterioration after surgery].

PMID- 19180693
TI  - Osler-Weber-Rendu syndrome: a case report with familial clustering.
AB  - Osler-Weber-Rendu syndrome, also known as hereditary hemorrhagic telangiectasia,
      is a rare autosomal dominant disorder manifested by telangiectases of the skin
      and mucous membranes and arteriovenous malformations of various organ systems. We
      present a case of Osler-Weber-Rendu syndrome with 11 affected members in her
      family.

PMID- 19180694
TI  - A brownish-red plaque in an adult.

PMID- 19180695
TI  - [Strep A test and ear irrigation].

PMID- 19180696
TI  - Key questions in ventilator management of the burn-injured patient (first of two
      parts).

PMID- 19180697
TI  - Dead-reckoning the distance between the National Burn Repository and a true
      population-based registry: a challenge and an opportunity.

PMID- 19180698
TI  - Study proposals for inhaled gases.

PMID- 19180700
TI  - Sea change.

PMID- 19180699
TI  - Use of nebulized heparin in the treatment of smoke inhalation injury.

PMID- 19180701
TI  - Surface tensions.

PMID- 19180702
TI  - Clement Kent.

PMID- 19180703
TI  - Scope-of-practice laws draw attacks.

PMID- 19180704
TI  - Mars recalls pet food because of potential link with human illness.

PMID- 19180705
TI  - Veterinarians alerted to new directions for Eqvalan Liquid for horses.

PMID- 19180706
TI  - AVMA, swine veterinarians respond to video of pig abuse.

PMID- 19180707
TI  - Getting the right drug at the right dosage. Personalized medicine brings
      precision to drug treatment.

PMID- 19180708
TI  - Information on Pew report on farm animal production.

PMID- 19180709
TI  - Questions information reported in ECG of the month.

PMID- 19180710
TI  - Does delayed renal failure exist?

PMID- 19180711
TI  - Can our food production system meet demand in a changing global society?
AB  - The worldwide demand for animal protein will grow as the world's population grows
      and the economies of developing countries evolve and mature. The veterinary
      profession must be a leader in advocating for responsible changes in production
      practices that will improve the welfare of food animals, ensure a safe and secure
      food supply, and minimize negative impacts on the environment.

PMID- 19180712
TI  - What is your diagnosis? Multiple epiphyseal dysplasia.

PMID- 19180713
TI  - Employment of female and male graduates of U.S. veterinary medical schools and
      colleges, 2008.
AB  - Mean starting salary among graduates of U.S. veterinary medical schools and
      colleges during 2008 was $51,321 for males and $47,330 for females. Mean debt for
      male graduates with debt was $115,059, whereas mean debt for female graduates
      with debt was $121,006.

PMID- 19180714
TI  - A survey of veterinarian involvement in zoonotic disease prevention practices.
AB  - OBJECTIVE: To determine the extent to which practicing veterinarians in King
      County, Washington, engaged in commonly recommended practices for the prevention
      of zoonotic diseases. DESIGN: Cross-sectional survey. Sample Population-Licensed
      veterinarians practicing clinical medicine in King County, Washington.
      PROCEDURES: A survey was sent between September and November 2006 to 454 licensed
      veterinarians practicing clinical medicine in King County. RESULTS: 370 valid
      responses were received. A high proportion (280/362 [77%]) of respondents agreed
      that it was very important for veterinarians to educate clients on zoonotic
      disease prevention, but only 43% (158/367) reported that they had initiated
      discussions about zoonotic diseases with clients on a daily basis, and only 57%
      (203/356) indicated that they had client educational materials on zoonotic
      diseases available in their practices. Thirty-one percent (112/360) of
      respondents indicated that there were no written infection-control guidelines for
      staff members in the practice, and 28% (105/371) reported having been infected
      with a zoonotic disease in practice. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      illustrated that veterinarians recognize their important role in zoonotic disease
      prevention and suggested that veterinarians would welcome stronger partnerships
      with public health agencies and other health professionals in this endeavor.
      Methods to increase veterinarians' involvement in zoonotic disease prevention
      include discussing zoonotic diseases more frequently with clients, physicians,
      and public health agencies; encouraging higher risk individuals to discuss
      zoonotic diseases; having educational materials on zoonotic diseases available
      for clients; improving infection-control practices; and ensuring that continuing
      education courses on zoonotic diseases are regularly available.

PMID- 19180715
TI  - Use of an electrothermal, feedback-controlled, bipolar sealing device for
      resection of the elongated portion of the soft palate in dogs with obstructive
      upper airway disease.
AB  - OBJECTIVE: To evaluate efficacy and safety of using an electrothermal, feedback
      controlled, bipolar sealing device (BSD) for resection of the elongated portion
      of the soft palate in brachycephalic dogs with upper airway obstruction. DESIGN:
      Uncontrolled clinical trial. ANIMALS: 24 brachycephalic dogs with airway
      obstruction and elongated soft palate. PROCEDURES: In all dogs, the excess
      portion of the soft palate was resected with a BSD. A score for severity of
      clinical signs of respiratory tract obstruction was assigned before surgery,
      during the first 24 hours after surgery, and at the time of final follow-up 12 to
      23 months after surgery. Potential scores ranged from 0 (no clinical signs even
      with moderate to vigorous activity) to 4 (agonal breathing or severe cyanosis).
      RESULTS: None of the dogs died or developed life-threatening complications after
      surgery. Clinical scores after surgery (mean +/- SD, 0.3 +/- 0.6) and at the time
      of final follow-up (0.9 + 0.5) were significantly lower than preoperative scores
      (2.6 +/- 0.8). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that a BSD
      can be safely used for resection of the elongated portion of the soft palate in
      brachycephalic dogs with upper airway obstruction.

PMID- 19180717
TI  - Primary hyperaldosteronism in a domestic ferret with an adrenocortical adenoma.
AB  - CASE DESCRIPTION: A 6-year-old spayed female domestic ferret was evaluated
      because of lethargy, alopecia, pruritus, and an abdominal mass. CLINICAL
      FINDINGS: On initial examination, nonregenerative anemia, mild azotemia, and a
      large left adrenal gland mass were identified. However, deterioration of the
      ferret's general condition prevented excision of the mass, and dyspnea, weakness,
      hypertension, and severe hypokalemia developed. Plasma aldosterone concentration
      was >3329 pmol/L, confirming a provisional diagnosis of hyperaldosteronism. High
      concentrations of sex hormones were also observed, but baseline cortisol
      concentration was within reference limits. TREATMENT AND OUTCOME: Medical
      treatment included oral administration of spironolactone, potassium gluconate,
      leuprolide acetate, amlodipine, and benazepril. Inhalation of albuterol proved
      effective in reducing the dyspnea. In the following weeks, serum potassium
      concentration returned to within reference limits and hypertension decreased, but
      dyspnea persisted. Two months after initial examination, the ferret became
      anorectic and was euthanized. Histologic examination revealed a large left
      adrenal gland adenoma, progressive chronic nephropathy, severe pulmonary edema,
      and focal fibrosis in the left ventricle. Immunohistochemical staining of the
      adrenal gland mass revealed aldosterone within neoplastic adrenocortical cells.
      CLINICAL RELEVANCE: Findings suggested that primary hyperaldosteronism should be
      considered as a possible cause in ferrets with hypokalemia, hypertension, and an
      adrenal gland mass. Early detection of aldosterone-secreting masses might allow
      for removal of the tumor before irreversible complications occur.

PMID- 19180718
TI  - Tracheal collapse in American Miniature Horses: 13 cases (1985-2007).
AB  - OBJECTIVE: To describe the clinical and laboratory findings, diagnostic features,
      and outcome of tracheal collapse in American Miniature Horses at a referral
      institution. DESIGN: Retrospective case series. ANIMALS: 13 American Miniature
      Horses with tracheal collapse. PROCEDURES: Medical records of American Miniature
      Horses with tracheal collapse at a referral hospital were reviewed. Data
      extracted included signalment, history, clinical signs, laboratory data,
      diagnostic procedures, outcome, and histologic findings. RESULTS: Tracheal
      collapse was documented in 5.6% of American Miniature Horses admitted to this
      referral hospital. Median age at onset of clinical signs was 11 years with a
      range of 2 to 15 years. Common complaints and clinical signs included respiratory
      distress, tachypnea, inspiratory honking noises, and increased abdominal
      expiratory effort, which were exacerbated by stressful events, pregnancy,
      exercise, a dusty environment, and eating. Tracheal collapse was confirmed by use
      of radiography, endoscopy, fluoroscopy, or postmortem examination. Dorsoventral
      flattening of the extra- or intrathoracic trachea, or both, was more common than
      lateral collapse. Tracheal chondromalacia was identified histologically in 4
      cases, and mortality rate for affected horses was 10 of 13. CONCLUSIONS AND
      CLINICAL RELEVANCE: Tracheal collapse was relatively common in this study of
      American Miniature Horses, and outcome was poor. The etiopathogenesis of the
      disease remains unknown.

PMID- 19180716
TI  - Ability of the canine brief pain inventory to detect response to treatment in
      dogs with osteoarthritis.
AB  - OBJECTIVE: To determine whether the Canine Brief Pain Inventory (CBPI) can detect
      changes in dogs with osteoarthritis treated with an NSAID or a placebo. DESIGN:
      Double-blind, randomized, placebo-controlled clinical trial. ANIMALS: 70 dogs
      with osteoarthritis. PROCEDURES: Owners completed the CBPI on day 0. Dogs
      received carprofen or a placebo on days 1 through 14. Owners completed the CBPI
      again on day 14. Pain severity and pain interference scores from the CBPI were
      calculated, and the change from day 0 to day 14 was assessed within each group
      and between groups. RESULTS: No significant differences were detected in median
      scores for pain severity (3.50 and 3.25 on days 0 and 14, respectively) and pain
      interference (3.92 and 3.25 on days 0 and 14, respectively) in dogs receiving the
      placebo. Dogs receiving carprofen had significant changes in median scores for
      pain severity (4.25 to 2.25 on days 0 and 14, respectively) and pain interference
      (4.33 to 2.67 on days 0 and 14, respectively).There was a significantly greater
      improvement in pain severity and pain interference scores in dogs treated with
      carprofen, compared with improvement in scores for dogs receiving the placebo.
      CONCLUSIONS AND CLINICAL RELEVANCE: The CBPI was able to detect improvements in
      pain scores in dogs with osteoarthritis treated with an NSAID or a placebo. These
      results, in combination with previous reliability and validity testing, support
      the use of the CBPI to obtain quantifiable assessments from owners regarding the
      severity and impact of chronic pain and treatment for dogs with osteoarthritis.

PMID- 19180719
TI  - Activity and participation in psychiatric institutional care.
AB  - National action plans emphasize the importance of strengthening the role of
      patients in health and medical care. Patients should feel that they can
      participate and that they are seen as a resource. In occupational therapy, the
      client-centred approach has developed, whereby it is key to enable patients to
      participate in their treatment. The International Classification of Functioning
      Disability and Health (ICF) has inspired this study, in which concepts such as
      activity and participation are central. The purpose of the study was to describe
      how patients in psychiatric institutional care conceive their opportunities to be
      active, and how they participate in their own treatment. Questionnaires were sent
      to patients who had received care during a six-month period. Ten patients were
      then selected for interview. The study shows that younger patients and patients
      who were treated involuntarily were generally more dissatisfied than other
      patients. The patients' perceptions of their environment were influenced by the
      values in the ward. Topics such as atmosphere in the ward, reception, continuity,
      and support were presented. Important factors related to activity and
      participation were: agreement concerning the treatment plan, discussions about
      expectations, creating conditions for engagement in activities, and providing the
      patients with opportunities to take responsibility for themselves.

PMID- 19180720
TI  - Cross-cultural validation of the Pediatric Evaluation of Disability Inventory
      (PEDI) norms in a randomized Norwegian population.
AB  - The Pediatric Evaluation of Disability Inventory (PEDI) is one of the most
      commonly used assessments for children with a disability. Normative data from the
      US are used to determine whether a deficit or delay exists with regard to
      functional skill development. The purpose of this study was to analyse the cross
      cultural validity of the PEDI American normative data for a general Norwegian
      population. A random selection of 174 typically developed Norwegian children
      between 1.0 and 5.9 years participated. The results for capability and caregiver
      assistance in the domains of self-care, mobility, and social function ranged from
      a mean of 38.0-46.8 against an expected 50. The Norwegian sample scored
      significantly lower than the US reference values for functional skills and
      caregiver assistance, and the results had less fit, especially for self-care. For
      mobility and social function, the magnitudes of the differences were smaller than
      self-care. Specific items deviated, suggesting necessary adjustments for the
      applicability of the norm-referenced scores of the PEDI in the Norwegian culture.
      The result of this research confirms other findings of cultural influence of the
      age norms in PEDI. Even though interpretations of the normative score results
      must be made with some caution, the option of using the scaled scores of PEDI is
      useful and recommended to describe and measure abilities and to evaluate change.
      This finding highlights the importance of cultural validation of norm-referenced
      tests.

PMID- 19180721
TI  - Participation at school as experienced by teenagers with physical disabilities.
AB  - The purpose of this study was to investigate the experiences that teenagers with
      physical disabilities have of their participation at school. Fourteen students
      from several locations in Norway aged between 13 and 18 years took part. Data
      were collected through focus-group interviews and individual interviews. The
      analysis revealed three main themes: Just like the others-but not quite;
      Participation in terms of being where things actually happen and; Participation
      as student-teacher cooperation. A major finding was the importance the students
      put on being where things actually happen, this being regarded as being even more
      important than doing the same activities as the other students. Opportunities to
      increase cooperation by holding short meetings with teachers on how to solve both
      practical and learning problems promoted participation. The need to include the
      individual's experience in the concept of participation is discussed.

PMID- 19180722
TI  - Participation by doing: social interaction in everyday activities among persons
      with schizophrenia.
AB  - Schizophrenia impacts on social functioning and participation in everyday life.
      However, there is limited research describing how persons with schizophrenia
      interact with others when performing daily activities. The aim of this study is
      to describe how persons with schizophrenia interact with others while performing
      everyday activities in different contexts in terms of facilitating and hindering
      factors. Repeated participant observations of four persons with schizophrenia
      were conducted in their environment. The observed activities and social
      interactions were chosen from the participant's daily routines. Field notes were
      taken during the observations. Qualitative content analysis was used to analyse
      the data. Two themes constitute the main result: Facilitating social interaction
      in activity performance and Hindering social interaction in activity performance.
      These two themes serve as headings for sub-themes representing factors
      influencing social interaction in activity performance. Through a further
      analysis of the themes the following dichotomous contexts were identified as
      influential: meaningful/not meaningful activity being performed; attitudes were
      trusting/lacking trust; and location, at home/outside the home. CONCLUSION: If
      the facilitating contextual factors are considered for each individual when
      planning and performing everyday activities together with others there is a
      possibility to improve social interaction skills and thereby participation.

PMID- 19180723
TI  - Effect of an intensive hand exercise programme in patients with rheumatoid
      arthritis.
AB  - The aim of this study was to test the effect of an intensive hand exercise
      programme in patients with rheumatoid arthritis (RA). Designed as a clinical
      controlled trial, the first 30 participants received a conservative exercise
      programme (CEP), while the next 30 received an intensive exercise programme
      (IEP). Outcomes were assessed at baseline, and after 2 and 14 weeks. Hand
      strength, measured as grip strength and pinch strength, was the primary outcome
      variable. Secondary outcomes were joint mobility, hand pain, and functional
      ability. After two weeks, there were significant differences between the groups
      in favour of the IEP in pinch strength in the dominant hand (p = 0.01), as well
      as grip and pinch strength in the non-dominant hand (p = 0.04 and 0.05,
      respectively). After 14 weeks, there was a significant difference between the two
      groups in grip strength in the non-dominant hand (p = 0.04), again in favour of
      the IEP. There was a trend towards increased pain in the CEP group and towards
      decreased pain in the IEP group, with significant differences between the groups
      in several measures of pain after 2 and 14 weeks. However, there were few
      significant differences between the two groups regarding joint mobility and
      functional ability. The results indicate that, compared with a traditional
      programme, an intensive hand exercise programme is well tolerated and more
      effective in improving hand function in patients with RA.

PMID- 19180724
TI  - The interaction of mannose binding lectin (MBL) with mannose containing
      glycopeptides and the resultant potential impact on invasive fungal infection.
AB  - Mannnose-binding lectin (MBL) binds oligosaccharides on the surface of
      microorganisms to form complexes that activate the complement cascade and
      facilitate phagocytosis. Teicoplanin and dalbavancin glycopeptide antibiotics
      possess N-acetyl glucosamine and mannose oligosaccharides that may bind MBL.
      Pharmaceuticals capable of binding to MBL may decrease clearance of significant
      pathogens such as yeast. An invasive candidemia murine model was utilized to
      evaluate differences in survival between mannose- and teicoplanin-treated groups
      compared to a control group administered normal saline. Three groups of BALB/c
      mice were injected with Candida albicans ATCC 44858 (1.4 x 10(6) CFU).
      Pharmaceutical agents were administered 2 h pre-infection and 8 h post-infection.
      In vivo cumulative survival at 52 h revealed 10%, 30% and 90% survival rates for
      mice administered mannose, teicoplanin, and saline, respectively. There was 0%
      survival for mice given mannose or teicoplanin at 56 h, compared with 70% for the
      normal saline treated mice at the same time point (P < 0.05). This in vivo study
      shows 'accelerated progression of infection' for Candida-inoculated mice exposed
      to mannose or teicoplanin compared to those given normal saline. Further, protein
      polyacrylamide gel electrophoresis studies suggested a potential MBL-drug
      interaction which may attenuate complement activation, opsonization and
      phagocytosis.

PMID- 19180725
TI  - Rhodotorula spp. isolated from blood cultures: clinical and microbiological
      aspects.
AB  - The emergence of less common fungal pathogens has been increasingly reported in
      the last decade. We describe 25 cases of Rhodotorula spp. isolated from blood
      cultures at a large Brazilian tertiary teaching hospital from 1996-2004. We also
      investigated the in vitro activity of four antifungal drugs, using a standardized
      method. The median age of patients was 43 years. The majority of patients (88%)
      had a central venous catheter (CVC) and 10 (40%) were recipients of a bone marrow
      transplant. The episode was classified as a bloodstream infection (BSI) in 80% of
      the patients. Amphotericin B deoxycholate was the most common antifungal used and
      CVC was removed in 89.5% of the patients. Death occurred in four patients
      (17.4%), all classified as BSI. All strains were identified as R. mucilaginosa by
      conventional methods. Misidentification of the species was observed in 20% and 5%
      of the strains with the Vitek Yeast Biochemical Card and API 20C AUX systems,
      respectively. Amphotericin B demonstrated good in vitro activity (MIC50/90, 0.5
      microg/ml) and the MICs for fluconazole were high for all strains (MIC50/90, >64
      microg/ml).

PMID- 19180726
TI  - Comparative in vitro activities of posaconazole, voriconazole, itraconazole, and
      amphotericin B against Aspergillus and Rhizopus, and synergy testing for
      Rhizopus.
AB  - We compared the in vitro activities of posaconazole, voriconazole, itraconazole,
      and amphotericin B against clinical isolates of Aspergillus spp. and Rhizopus
      spp., and explored the in vitro interaction between posaconazole and amphotericin
      B against Rhizopus spp. Clinical strains of 82 Aspergillus spp. (43 Aspergillus
      fumigatus, 29 A. flavus, 7 A. niger, 2 A. terreus, 1 A. nidulans) and 11 Rhizopus
      oryzae isolates were tested in accordance with CLSI M38-A microdilution
      guidelines. In vitro activity of posaconazole against Aspergillus spp. was also
      investigated with the Etest. The combination of posaconazole and amphotericin B
      against R. oryzae isolates was investigated by the checkerboard methodology.
      Voriconazole was the most active drug in vitro against Aspergillus spp., followed
      by posaconazole, itraconazole, and amphotericin B, in order of decreasing
      activity. In studies with R. oryzae isolates, posaconazole was found to be the
      most potent drug followed by itraconazole and amphotericin B. Voriconazole had no
      meaningful activity against Rhizopus. Posaconazole Etest MICs (microg/ml) with
      Aspergillus spp. were found to be considerably lower than those obtained with the
      CLSI microdilution method (4-9 and 3-7 two-fold lower than CLSI MICs at 24 and 48
      h, respectively). The interaction between posaconazole and amphotericin B was
      indifferent for all R. oryzae isolates tested; importantly no antagonism was
      observed.

PMID- 19180727
TI  - Seven-year trend analysis of nosocomial candidemia and antifungal (fluconazole
      and caspofungin) use in Intensive Care Units at a Brazilian University Hospital.
AB  - Candidemia is associated with high morbidity and mortality resulting in
      significant increases in the length of patients' hospitalization and in
      healthcare costs. Critically ill patients are at particular risk for candidemia
      because of their debilitated condition and frequent need for invasive procedures.
      The aim of this study was to characterize the incidence and epidemiology of
      candidemia over a seven-year period in intensive care units (ICUs) and the use of
      fluconazole and caspofungin in a large university-affiliated hospital. All cases
      of candidemia were identified by surveillance, using the Centers for Diseases
      Control and Prevention criteria. Demographic variables, use of antifungal
      (fluconazole and caspofungin) and patient outcomes were evaluated. The chi2 test
      for linear trend was employed to evaluate the distribution of Candida spp. and
      the use of fluconazole and caspofungin by defined daily dose (DDD) per 1,000
      patients-days during the study period. One hundred and eight episodes of
      candidemia were identified. The overall incidence of candidemia (P=0.20) and
      incidence of non-Candida albicans Candida infections (P=0.32) remained stable
      over the study period and ranged from 0.3-0.9 episodes per 1,000 catheter-days
      and 0.39-0.83 episodes per 1,000 patients-days. However, the use of fluconazole
      and caspofungin increased significantly (P<0.001). While there were no reports of
      the use of fluconazole for prophylaxis in 1999, its use for this purpose
      increased from 3% in 2000 to 7.0% (P=0.07) in 2006. C. albicans was the most
      frequent specie isolated and burns and cancer were the most frequent underlying
      conditions. The overall mortality was 76%. There was no difference between C.
      albicans and non-C. albicans Candida infections when the crude and 14-day
      mortality rates were compared. Our data demonstrated that C. albicans is still
      the most frequent species causing candidemia in our intensive care units. Our
      rates of candidemia are lower than those reported from the region and similar to
      American and European hospitals. Although the incidence of blood stream
      infections (BSI) and candidemia remained stable, the use of fluconazole and
      caspofungin increased significantly over the years included in this study but had
      no impact on the incidence of infections caused by non-C. albicans Candida
      species.

PMID- 19180728
TI  - A case of pulmonary cryptococcosis followed by pleuritis in an apparently
      immunocompetent patient during fluconazole treatment.
AB  - Cryptococcal pleuritis is rare in individuals with no underlying disease. We
      report a case of pulmonary cryptococcosis followed by pleuritis in a patient on
      fluconazole treatment. Biopsy of the pleura revealed a granuloma and a
      cryptococcal body, while PCR and sequence analysis of extracted DNA from the
      pleura proved the presence of Cryptococcus species, most likely C. neoformans.
      Voriconazole with flucytosine and drainage of the pleural effusion were effective
      in treating the patient.

PMID- 19180729
TI  - Molecular characterization of Alternaria alternata causing ocular infection:
      detection of IGS-RFLP intraspecific polymorphism.
AB  - A case of fungal keratitis is presented in which corneal scrapings were obtained
      for microbiological studies, including morphological identification and molecular
      characterization of the etiologic agent. Comparative sequence analyses of the
      Internal Transcribed Spacer domain of 5.8S and 26S regions of nuclear rDNA showed
      100% identity with different species of Alternaria and PCR-RFLP analysis of
      Intergenic Spacer regions revealed intraspecific variation. The combination of
      morphological and molecular characters resulted in the unambiguous identification
      of the causal agent as Alternaria alternata. Treatment with antifungals
      contributed to the improvement in the patient's lesions.

PMID- 19180730
TI  - [Current status of epidemiological studies on earthquake related suicide].

PMID- 19180731
TI  - [Advance in immunization of hepatitis B vaccine research].

PMID- 19180732
TI  - [The advance on the study of Mycobacterium tuberculosis Beijing/W family
      strains].

PMID- 19180733
TI  - [Epidemiological analysis on serogroup W135 Neisseria meningitidis firstly
      isolated from patient in Guangdong province].

PMID- 19180734
TI  - [Study on risk factors and serologic status among brucellosis inapparent
      infection farmers in Tianjin, 2007].

PMID- 19180735
TI  - [An analysis on the quality of information regarding online reporting system of
      notifiable diseases in Zhoushan city, Zhejiang province in 2007 ].

PMID- 19180736
TI  - [Survey on the reproductive health status of married minority men at reproductive
      age in rural areas of Guizhou province].

PMID- 19180737
TI  - [Open cholecystectomy under thoracic epidural anesthesia in patients with severe
      lung disease].

PMID- 19180738
TI  - Time for adolescent medicine units in South Africa?

PMID- 19180739
TI  - [Weakened professional role of the anesthetist?].

PMID- 19180740
TI  - Signalling mechanisms.

PMID- 19180741
TI  - Oral Pathology Quiz #61. Case number 3. Periapical cemento-osseous dysplasia.

PMID- 19180742
TI  - Oral Pathology Quiz #61. Case number 4. Osteosarcoma.

PMID- 19180743
TI  - After bariatric surgery.

PMID- 19180744
TI  - Two schools of thought.

PMID- 19180745
TI  - Two schools of thought.

PMID- 19180746
TI  - ANCC responds to blog comment.

PMID- 19180747
TI  - Responses to AFP journal club on hip fracture and PPI use.

PMID- 19180748
TI  - Cell mediated immunity to fungi: a reassessment.
AB  - Protective immunity against fungal pathogens is achieved by the integration of
      two distinct arms of the immune system, the innate and adaptive responses. Innate
      and adaptive immune responses are intimately linked and controlled by sets of
      molecules and receptors that act to generate the most effective form of immunity
      for protection against fungal pathogens. The decision of how to respond will
      still be primarily determined by interactions between pathogens and cells of the
      innate immune system, but the actions of T cells will feed back into this dynamic
      equilibrium to regulate the balance between tolerogenic and inflammatory
      responses. In the last two decades, the immunopathogenesis of fungal infections
      and fungal diseases was explained primarily in terms of Th1/Th2 balance. Although
      Th1 responses driven by the IL-12/IFN-gamma axis are central to protection
      against fungi, other cytokines and T cell-dependent pathways have come of age.
      The newly described Th17 developmental pathway may play an inflammatory role
      previously attributed to uncontrolled Th1 responses and serves to accommodate the
      seemingly paradoxical association of chronic inflammatory responses with fungal
      persistence in the face of an ongoing inflammation. Regulatory T cells in their
      capacity to inhibit aspects of innate and adaptive antifungal immunity have
      become an integral component of immune resistance to fungi, and provide the host
      with immune defense mechanisms adequate for protection, without necessarily
      eliminating fungal pathogens which would impair immune memory--or causing an
      unacceptable level of tissue damage. The enzyme indoleamine 2,3-dioxygenase and
      tryptophan metabolites contribute to immune homeostasis by inducing Tregs and
      taming overzealous or heightened inflammatory responses.

PMID- 19180749
TI  - Candida lusitaniae fungemia in cancer patients: risk factors for amphotericin B
      failure and outcome.
AB  - Candida lusitaniae, a Candida species frequently resistant to amphotericin B
      (AMB), is a rare cause of candidemia. The clinical significance of this in vitro
      resistant phenotype, the risk factors for, and the clinical presentation of C.
      lusitaniae fungemia in comparison with those of Candida albicans have not been
      completely characterized. We reviewed 13 consecutive cases of C. lusitaniae
      fungemia in cancer patients and compared them with 41 consecutive cases of C.
      albicans fungemia (1990-2004). The AMB mutational frequency and rate of
      fungicidal activity was compared between a bloodstream, AMB-susceptible C.
      lusitaniae isolate associated with clinical failure and reference C. albicans and
      Candida glabrata strains. In multivariate analysis, patients having C. lusitaniae
      fungemia were more likely to have neutropenia (p=0.001), stem cell
      transplantation (p=0.014) and to have received prior antifungals (p=0.04).
      Mutational frequencies at clinically-achievable AMB exposures were 8 x 10(5) for
      C. lusitaniae and <1 x 10(9) for C. albicans and C. glabrata reference strains.
      Compared to C. albicans and C. glabrata, AMB had much less fungicidal activity
      against C. lusitaniae in time-kill curve analysis. Clinically, C. lusitaniae
      fungemia was more frequently associated with stem cell transplant and
      neutropenia. C. lusitaniae, even originally susceptible to AMB, might be less
      amenable to AMB therapy.

PMID- 19180750
TI  - Morphological and molecular characterization of an equine isolate of Pythium
      insidiosum and comparison with the first human isolate from the same geographic
      region.
AB  - Pythium insidiosum causes pythiosis, a life-threatening disease that occurs in
      tropical regions and affects man and animals. Although pythiosis in Brazil had
      been described in various animal species, the first human case was only recently
      reported. The present study aimed to characterize the morphologic and molecular
      characteristics of a new equine isolate of P. insidiosum and compare them with
      those of the first Brazilian human isolate. Both isolates were recovered from the
      same region of the country. Macroscopic and microscopic features were evaluated
      in two culture media. Sporangia formation and zoospore release were obtained
      after culturing the isolates with fragments of grasses and crops in an
      appropriate liquid induction medium. The molecular analysis of the isolates
      consisted of the complete sequencing of the ITS-5.8S rDNA region and sequences of
      both showed identical composition of 836 bp and 99% similarity with the isolates
      M16, 65, M12, 339 and 394 deposited at GenBank. Simple mycological procedures
      such as the production of sporangia and zoospores may distinguish P. insidiosum
      from zygomycetes. The rDNA sequencing indicates that, in Brazil, both humans and
      animals might be infected by a common genotype of the pathogen.

PMID- 19180751
TI  - Value of a single galactomannan determination (Platelia) for the diagnosis of
      invasive aspergillosis in non-hematological patients with clinical isolation of
      Aspergillus spp.
AB  - We studied 75 patients with non-hematological conditions from whom Aspergillus
      spp. were recovered from clinical specimens during the period March 2003 to
      August 2006. The patients were classified according to EORTC criteria and the
      presence of galactomannan (Platelia Aspergillus) in their sera was evaluated. Ten
      of these patients (13.3%) had proven or probable invasive aspergillosis, i.e.,
      chronic obstructive pulmonary disease in five (50%), HIV infection in one (10%),
      lymphoma in one (10%), liver transplant in one (10%), solid malignancies in one
      (10%), and corticosteroid treatment in one (10%). The sensitivity, specificity,
      and positive and negative predictive values for the detection of galactomannan,
      using cut-offs of > or =0.5 ng/ml and > or =1 ng/ml were 60%/50%, 89.23%/100%,
      46.15%/100%, and 93.55%/92.86% (p=0.001 and p<0.001), respectively. The
      determination of galactomannan in the sera of non-neutropenic patients could
      prove to be a useful microbiological finding when diagnosing invasive
      aspergillosis.

PMID- 19180753
TI  - Sporothrix luriei: a rare fungus from clinical origin.
AB  - Sporothrix schenckii var. luriei is a very rare pathogen reported on four
      occasions from human infections, but only isolated from one case in Africa. Here,
      it is proposed as a species different from Sporothrix schenckii on the basis of
      phenotypic characteristics and a multilocus sequence analysis.

PMID- 19180752
TI  - Back pain associated with endobronchial mucus impaction due to Bipolaris
      australiensis colonization representing atypical Allergic Bronchopulmonary
      Mycosis.
AB  - A 40-year-old white male had a two-year history of right sided upper back pain
      without dyspnea or coughing. His past history was significant for allergic
      rhinitis and asthma. Conservative outpatient management of the back pain
      including medications, rest and physical therapy were ineffective. CT scan of the
      chest revealed a mass in the lower lobe of the right lung. Bronchial biopsy and
      lavage revealed eosinophilic and neutrophilic inflammation without tissue
      invasion. A pure culture of Bipolaris australiensis was confirmed by DNA typing.
      Hematological, serological and radiological studies were not compatible with
      Allergic Bronchopulmonary Mycosis (ABPM), fungus ball, hypersensitivity
      pneumonitis or invasive fungal infection. However, the mucus plugging may have
      represented an atypical localized form of ABPM. Resolution of the endobronchial
      mucus impaction occurred after three bronchoscopies with vigorous suction, anti
      fungal therapy and prednisone.

PMID- 19180754
TI  - Characteristics of the parallel-plate flow chamber for mechanical stimulation of
      bone cells under microgravity.
AB  - We show the use of a dimensionless parameter alpha h, in properly downscaling a
      parallel-plate flow chamber system for flow stimulation of bone cells under
      microgravity. The proper experimental regime for exposing cells to predictable
      levels of dynamic fluid shear stress requires: 1) alpha h < 2, based on the
      consequent quasi-parabolic form of the velocity profile in this regime, and 2) fo
      m<fc, where the critical frequency fc is the upper threshold for this flow
      regime, m is the highest harmonic mode of the flow, and fo is the fundamental
      frequency of fluid flow.

PMID- 19180755
TI  - Health tips.  Stretching like the pros.

PMID- 19180756
TI  - Brain imaging can detect chronic grief.

PMID- 19180757
TI  - PSA tests. The latest developments.

PMID- 19180759
TI  - How does eating broccoli slaw compare nutritionally with eating broccoli heads?

PMID- 19180758
TI  - Dry eyes.  Grit be gone.

PMID- 19180760
TI  - The expansion of the nuclear family unit in Great Britain between 1910 and 1920.

PMID- 19180761
TI  - The limits of policy: rural children and work in the United States and New
      Zealand, 1870-1920.

PMID- 19180763
TI  - Family enterprise in the Baltic estate economy: the nineteenth century.

PMID- 19180762
TI  - The temporary migration of males and the power of females in a stem-family
      society: the case of 19th-century Auvergne.

PMID- 19180764
TI  - Family and business among master artisans and entrepreneurs: the case of 19th
      century Vienna.

PMID- 19180765
TI  - Women, family, and small business in late nineteenth century Sweden.

PMID- 19180766
TI  - Regional standardization in the age at marriage: a comparative study of
      preindustrial Germany and Japan.

PMID- 19180768
TI  - Global Advisory Committee   on Vaccine Safety,   17-18 December 2008.

PMID- 19180767
TI  - Alien encounters: the jus soli and reproductive politics in the 19th-century
      fortress and colony of Gibraltar.

PMID- 19180769
TI  - The cost of educating children: the accounts of a nineteenth century girls'
      boarding school in Orleans, France.

PMID- 19180770
TI  - Mortality responses to rice price fluctuations and household factors in a farming
      village in central Tokugawa Japan.

PMID- 19180771
TI  - Familial strategies of artisans during the modernization process: Barcelona, 1814
      1860.

PMID- 19180772
TI  - Early marriage in pre-modern France.

PMID- 19180773
TI  - [Various problems in spacer inhalers].

PMID- 19180774
TI  - [Improved survival after out-of-hospital cardiac arrest in Copenhagen--secondary
      publication].

PMID- 19180775
TI  - [SORT OUT II--a randomized study of drug-eluting coronary stents--secondary
      publication].

PMID- 19180776
TI  - [Throat culture].

PMID- 19180777
TI  - [Sense of humor prolongs life].

PMID- 19180778
TI  - [Has "equal access to health care" disappeared, or what has become of it?].

PMID- 19180779
TI  - [Current resuscitation guidelines].

PMID- 19180780
TI  - [Guidelines in suspected colorectal cancer].

PMID- 19180781
TI  - [Thanks to health personnel].

PMID- 19180782
TI  - [How to document contact with the patient?].

PMID- 19180785
TI  - [On the 80th birthday of professor Pavel Vasil'evich Dunaev].

PMID- 19180786
TI  - [Proceedings and abstracts of the International Histological Conference
      "Morphogenesis in Evolution, Individual Development, and in Experimental Studies"
      dedicated to the 80th birthday of the honored scientist of the Russian Federation
      Professor Pavel Vasil'evich Dunaev].

PMID- 19180787
TI  - [Painful peripheral neuropathy].

PMID- 19180788
TI  - [Paraneoplastic peripheral neuropathy due to solid cancers].

PMID- 19180789
TI  - [Infectious mononeuropathy].

PMID- 19180790
TI  - Get the flu shot, not the flu!

PMID- 19180791
TI  - Focus on workforce planning.

PMID- 19180792
TI  - The forgotten nursing specialty: occupational health nursing.

PMID- 19180793
TI  - Needle-stick injuries.

PMID- 19180794
TI  - Salidroside from Rhodiola sachalinensis protects neuronal PC12 cells against
      cytotoxicity induced by amyloid-beta.
AB  - The amyloid beta-peptide (Abeta)-induced oxidative stress is a well-established
      pathway of neuronal cell death in Alzheimer's disease (AD). Salidroside, one of
      the major compounds from the roots of Rhodiola species (Crassulaceae), was
      investigated in vitro for its cytoprotection against Abeta-induced toxicity on
      rat neuronal PCl2 cells. Salidroside significantly reduced Abeta-induced
      cytotoxicity in a dose-dependent manner. Salidroside also reduced Abeta-mediated
      intracellular accumulation of reactive oxygen species and malondialdehyde (MDA),
      a product of lipid peroxides, by preventing Abeta-induced decline of antioxidant
      enzyme activities. These results suggest that salidroside protects neuronal PC12
      cells from Abeta-induced cytotoxicity via its antioxidant pathway.

PMID- 19180795
TI  - Natural killer cell activity, lymphocyte proliferation, and cytokine profile in
      tumor-bearing mice treated with MAPA, a magnesium aggregated polymer from
      Aspergillus oryzae.
AB  - The present study examined the effects of MAPA, an antitumor aggregated polymer
      of protein magnesium ammonium phospholinoleate-palmitoleate anhydride, isolated
      from Aspergillus oryzae, on concanavalin A (Con A)-induced spleen cell
      proliferation, cytokine production and on natural killer (NK) cell activity in
      Ehrlich ascites tumor-bearing mice. The Ehrlich ascites tumor (EAT) growth led to
      diminished mitogen-induced expansion of spleen cell populations and total NK
      activity. This was accompanied by striking spleen enlargement, with a marked
      increase in total cell counts. Moreover, a substantial enhancement in IL-10
      levels, paralleled by a significant decrease in IL-2 was observed, while
      production of IL-4 and interferon-gamma (IFN-gamma) was not altered. Treatment of
      mice with 5 mg/kg MAPA for 7 days promoted spleen cell proliferation, IL-2
      production and NK cell activity regardless of tumor outgrowth. In addition, MAPA
      treatment markedly enhanced IFN-gamma levels and reduced IL-10 production
      relative to EAT mice. A 35% reduction in splenomegaly with normal number of
      nucleated cells was also found. Altogether, our results suggest that MAPA
      directly and/or indirectly modulates immune cell activity, and probably
      disengages tumor-induced suppression of these responses. Clearly, MAPA has an
      impact and may delay tumor outgrowth through immunotherapeutic mechanisms.

PMID- 19180796
TI  - Enhanced cytokine synthesis of leukocytes by a beta-glucan preparation, SCG,
      extracted from a medicinal mushroom, Sparassis crispa.
AB  - Sparassis crispa is edible mushroom recently cultivable in Japan. It contains
      significantly high content (approximately 40%) of 6-branched 1,3-beta-D-glucan
      showing antitumor activity in mice. We recently purified a beta-glucan
      preparation designated as "SCG." It was considered worth while to test SCG in
      vitro with whole blood collected from human volunteers. The present study is
      focusing on the cytokine productivity of SCG in an in vitro human system. The
      following results were observed: (i) SCG dose dependently enhanced IL-8 synthesis
      of whole blood cell culture of human peripheral blood. (ii) IL-8 synthesis was
      enhanced in both PBMC and PMN cultures. (iii) IL-8 synthesis was induced in the
      culture with autologous plasma, but significantly reduced after 56 degrees C
      treatment. (iv) The activity was also weak in heat inactivated fetal calf serum
      (FCS). (v) A complement fragment, C5a, was released by SCG dependently upon dose
      and kinetics. (vi) Anti-SCG natural antibody was detected in human plasma. From
      these facts, SCG was observed to have the capacity to activate human leukocytes
      and related immune system.

PMID- 19180797
TI  - Effect of piperine on the inhibition of nitric oxide (NO) and TNF-alpha
      production.
AB  - Effect of piperine which is an alkaloid present in plants such as Piper nigrum
      and Piper longum on the production of nitric oxide (NO) and tumor necrosis factor
      alpha (TNF-alpha) level was analyzed using in vitro as well as in vivo systems.
      The level of nitrite in the LPS stimulated Balb/C mice (95.3 microM) was reduced
      in the piperine treated animals (25 microM) significantly. Nitrite level in the
      Concanavalin-A (Con-A) treated control animals (83.1 microM) was also
      significantly reduced to 18.5 microM in the piperine treated mice. The
      drastically elevated levels of TNF-alpha in the lipopolysaccharide (LPS)
      stimulated animals (625.8 pg/mL) was lowered in the piperine treated animals
      (105.8 pg/mL). Piperine also inhibited the Con-A induced TNF-alpha production.
      Piperine could inhibit the nitrite production by in vitro activated macrophages
      (116.25 microM) to the normal level (15.67 microM) at concentration of 5
      microg/mL. In vitro L929 bioassay also revealed the inhibition of TNF-alpha
      production by the piperine treatment.

PMID- 19180798
TI  - Interleukin-1 and tumor necrosis factor-alpha induce collagenolysis and bone
      resorption by regulation of matrix metalloproteinase-2 in mouse calvarial bone
      cells.
AB  - Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) greatly
      induces osteoclast formation and stimulates bone resorption of mouse calvaria in
      culture. We examined the effects of the two cytokines on the collagenolysis and
      bone resorption by induction of matrix metalloproteinases (MMPs). The cells were
      analyzed using zymographic analysis. It was shown that the mouse calvarial
      osteoblasts constitutively synthesize progelatinase-A (MMP-2). Interleukin-1beta
      markedly enhanced the messenger RNAs (mRNAs) expression of MMP-2 (gelatinase A),
      but slightly MMP-9 (gelatinase B), which associated with increases in bone matrix
      degradation. Both pro- and active-forms of MMP-2 were detected in the conditioned
      medium collected from calvarial cultures, and IL-1beta markedly stimulated both
      pro- and active-forms of the MMP-2. The expression of MMP-2 mRNAs could be
      detected, and they were markedly enhanced by IL-1beta on days 1 and 2. These
      results demonstrate that the potency of induction of MMP-2 by IL-1beta and TNF
      alpha is closely linked to the respective bone-resorbing activity, suggesting
      that MMP-2-dependent degradation of bone matrix plays a key role in bone
      resorption induced by these cytokines. On the other hand, when the mouse
      osteoblasts were stimulated with parathyroid hormone, 1,25(OH)2D3, mononuclear
      cell conditioned medium (MCM) and IL-1 as bone resorption agents, collagenolysis
      was increased by producing the active gelatinase. Interleukin-1 in stimulating
      bone resorption was examined using fetal mouse long bone organ culture.
      Interleukin-1 stimulated bone resorption and produced marked resorption when
      present simultaneously. Furthermore, treatment of indomethacin and dexamethasone
      clearly abolished the responses of IL-1alpha and IL-1beta.

PMID- 19180799
TI  - Immune tolerance to drugs. I. Long-term tolerability of rokitamycin in patients
      with antibiotics hypersensitivity.
AB  - Macrolides are considered one of the safest anti-infective groups in clinical use
      and are well-tolerated as alternative antibiotics in patients with a previous
      adverse reaction to other classes of antibiotics. However there is scarce
      information in the literature about their long-term tolerability. The present
      study was performed to determine whether the results of a challenge test with
      rokitamycin could predict the response to ingestion of rokitamycin during
      illness. The study was carried out on 335 patients, who experienced adverse
      reactions to one or more antibiotics. All patients received peroral challenges
      with rokitamycin (granules or capsules). On the first day patients received a
      number of placebo doses equivalent to the rokitamycin doses. One week later, the
      test was administered by increasing doses of rokitamycin at 60 min intervals
      until the common daily therapeutic dose of 406.25mg was reached (31.25-93.75-125
      156.25mg). A questionnaire was distributed to all subjects. In particular,
      subjects were asked to clarify any reactive symptom they had developed after
      ingestion of the drug. It was found that only 3.1% (4/129) of subjects, who used
      this drug, reported adverse reactions: three experienced urticaria/angioedema and
      one patient experienced erythema multiforme during treatment. This study, points
      out a low percentage of adverse reactions to rokitamycin after a negative
      challenge test, thus, emphasizing both safety and good predictive value as a
      challenge test.

PMID- 19180800
TI  - Anti-inflammatory activity of Korean folk medicine purple bamboo salt.
AB  - Purple bamboo salt is a specially processed salt according to the traditional
      recipe using normal salt and bamboo. It has been used for the purpose of
      prevention and treatment of various diseases in Korea. We investigated the anti
      inflammatory activity of purple bamboo salt by using human mast cell line (HMC
      1). Purple bamboo salt (1 mg/mL) inhibited phorbol 12-myristate 13-acetate (PMA)
      plus calcium ionophore A23187-stimulated tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-1beta and IL-6 secretion, by 67.04% +/- 0.08%, 68.01% +/- 1.85%,
      and 69.48% +/- 0.54%, respectively. In addition, the expression of TNF-alpha mRNA
      in HMC-1 cells was inhibited by purple bamboo salt under the same condition. When
      NaCl (1 mg/mL) was added, the secretion of TNF-alpha and IL-6 was also inhibited
      but the effect was markedly lower than purple bamboo salt. Our results suggest
      that purple bamboo salt importantly contributes to the prevention or treatment of
      inflammatory diseases.

PMID- 19180801
TI  - Changes in plasma level of human leukocyte elastase during leukocytosis from
      physical effort.
AB  - Physical exercise is known to induce immunological changes, mainly leukocytosis
      and neutrophil activation. However, it is not known to what extent the
      leukocytosis, observed after exertion, is associated with an increase in plasma
      neutrophil elastase, an early marker of inflammatory response and neutrophil
      degranulation. In the present study changes in circulating leukocyte and
      neutrophil counts and human neutrophil elastase plasma levels were evaluated in
      volley-ball players before and after 2 h and 12 h prolonged training, during a
      competition season. For comparison, the same parameters were evaluated in
      untrained subjects before and after a jogging session. Basal white blood cell
      WBC, polymorpho nuclear PMN, and human polymorpho nuclear-elastase PMN-ELA values
      were within the normal healthy reference range and no significant differences
      were found between the two groups studied. Venous blood samples of nine volley
      ball players showed a statistically significant increase in blood WBCs after 2 h
      exercise. This effect was paralleled by a statistically significant increase in
      PMN-ELA concentration compared to the values observed in the same individuals at
      rest. The exercise did not significantly change the basal correlation parameters
      between PMN level and PMN-ELA concentration. More pronounced WBC, PMN, and PMN
      ELA increases were observed in the seven inactive subjects after 2 h jogging.
      There was no linear correlation between increased PMN counts and increased PMN
      ELA concentrations in untrained subjects after exercise. The results show that
      not only the leukocyte count but also PMN-ELA plasma levels can be higher after
      physical effort. This has a practical significance as regards differential
      diagnosis demonstrating that determination of these two laboratory parameters can
      give abnormally high values even in the absence of an existing inflammatory
      process. Besides, lack of correlation between PMN count and PMN-ELA plasma levels
      in the untrained group suggest a state in which activation of the neutrophils is
      not connected with their number in peripheral blood.

PMID- 19180802
TI  - Anti-immunoglobulin responses to IgG, F(ab')2, and Fab botulinum antitoxins in
      mice.
AB  - Side effects to botulinum antitoxins, including anaphylaxis and serum sickness,
      are common. This is due to the immunogenicity of the antitoxin, which can be
      measured by the production of anti-immunoglobulin antibodies. An ideal botulinum
      antitoxin would elicit a minimal production of anti-immunoglobulin antibodies
      from a patient, aiding its safety. To investigate the immunogenicity of different
      immunoglobulin fragments, whole IgG, F(ab')2 and Fab botulinum antitoxins were
      administered to mice by either the intravenous or intramuscular route. The
      production of anti-immunoglobulin antibodies was measured over time after a
      single dose of antitoxin, and the anti-immunoglobulin antibodies isotyped. When
      administered by the intramuscular route, Fab showed significantly lower
      immunogenicity than IgG, while F(ab')2 had an immunogenicity that was
      intermediate between the two. When administered by the intravenous route there
      was no significant difference in immunogenicity between IgG and F(ab')2
      antitoxins, although Fab antitoxin had a significantly lower immunogenicity than
      either IgG or F(ab')2. IgG antitoxin was significantly more immunogenic by the
      intramuscular route than by the intravenous route. Sheep IgG had a lower
      immunogenicity than goat IgG in mice. There was no significant difference in
      immunogenicity between the two dosing routes for either F(ab')2 or Fab antitoxin.
      The anti-antibodies were predominantly IgG1, suggesting a strong Th2 bias to the
      anti-antibody response. In all cases, Fab represents the least immunogenic form
      of antitoxin.

PMID- 19180803
TI  - Subchronic exposure to ellagic acid impairs cytotoxic T-cell function and
      suppresses humoral immunity in mice.
AB  - Ellagic acid (EA) is present in a variety of foods such as grapes, strawberries,
      raspberries, and nuts. It is a dietary plant phenol that has been shown to
      inhibit oxidative stress and chemical carcinogenesis. Although several studies
      have examined the protective mechanisms of dietary EA including the induction of
      detoxifying enzymes, regulation of cell cycle, chelation of nickel, and
      prevention of DNA methylation, none have addressed the role of EA in
      immunological surveillance. This study investigates the status of immune function
      in B6C3F1 mice exposed continuously to EA in drinking water at 0.5, 1.0, or 2.0
      mg/kg/day for 28 days. Although this range of exposure is above the estimated
      human daily intake (approximately 940 microg/day for 70 kg person or 13.4
      microg/kg/day), these levels would not be unreasonable if EA were used as a
      dietary supplement or as a chemotherapeutic agent. Previous reports have
      demonstrated the anticarcinogenic effects of EA at levels 10- to 250-fold greater
      than those applied in this study. Immunological parameters assessed included
      natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity, IgM
      antibody plaque forming cell (PFC) response, thymus, spleen, kidney, and liver
      mass, and total cellularity for the thymus and spleen. Subchronic exposure to EA
      for 28 days in drinking water caused significant suppression of specific IgM
      antibody responses in the 2.0 mg/kg EA treatment group and suppressed cytotoxic T
      cell function in the 0.5 and 1.0 mg/kg EA treatment groups. All other
      immunological parameters were within normal ranges. Kidney and liver mass were
      not altered after treatment with EA. The results from this study indicate that EA
      suppressed both IgM antibody responses and CTLs. These observations suggest
      important implications on human health should EA be prescribed as a
      chemotherapeutic agent or a preventative dietary supplement for cancer.

PMID- 19180804
TI  - The immunostatus of T helper and T cytotoxic cells in the patients ten years
      after exposure to sulfur mustard.
AB  - The treatment and cure of patients exposed to sulfur mustard is a remaining
      challenge despite ongoing research in this field. A severe suppression of the
      immune system still remains the major cause of opportunistic infections,
      septicemia, and death in these patients. The patients evaluated in this study
      were classified into three groups; severe, moderate, and mild according to the
      severity of exposure to sulfur mustard. We measured the total leukocyte and the
      status of T helper and T cytotoxic cells in such patients 10 year after being
      exposed to sulfur mustard. The total leukocyte was measured by using anti CD45+
      and the amount of T helper and T cytotoxic were evaluated by anti CD3, anti CD4,
      and anti CD8, while the activity of T helper was measured by anti CD4 and anti
      CD25. T helper and T cytotoxic cells were evaluated in lymphocyte and leukocyte
      gates through forward scatter and side scatter flow cytometer. The results showed
      that the percentage of CD45+ were normal in all of the groups while the
      percentage of T helper and T cytotoxic cells were significantly (P < 0.05)
      decreased in the severe group comparing to mild group. Also the results indicate
      that CD4+/CD25+ cells in the most severely affected patients were significantly
      (P < 0.05) increased comparing to the other groups. Ten years following exposure
      to sulfur mustard, the immune system of the patients is still impaired and this
      might be related to their present health problems.

PMID- 19180805
TI  - Immune response of E. cuniculi infected mice to aflatoxin B1.
AB  - The immunomodulatory effects of aflatoxin B1 (AFB1) on mice experimentally
      infected with Encephalitozoon cuniculi (E. cuniculi) were studied. Mice
      inoculated intraperitoneally with spores of E. cuniculi drank a daily solution of
      AFB1 (0.2 mg kg(-1) of body weight) for 27 days. Application of AFB1 to mice
      demonstrated a decrease of immunocompetent cells. On the other hand, the mice
      infected with E. cuniculi and given AFB1 showed significant increased number of
      both monocytes and CD8+ T cells, and tendency to a decrease in CD4+ T cells.
      Aflatoxin B1 revealed to merely modulate systemic immune response of E. cuniculi
      infected mice.

PMID- 19180806
TI  - Effect of some mycotoxins on superoxide anion production of isolated human
      neutrophils and in whole blood.
AB  - Activity of mycotoxins citrinin, ochratoxin B, rubratoxin B, and zearalenol beta
      was studied on human neutrophils with regard to O2- generation. At the doses of
      10(-8), 10(-6), 10(-4), or 10(-2) mg/mL the mycotoxins stimulated the superoxide
      anion production in resting neutrophils in whole blood but inhibited it in
      isolated cells. In neutrophils stimulated with zymosan or PMA, mycotoxins showed
      inibiting effect both on isolated and in whole blood cells. The behavior of
      resting isolated neutrophils, identical to that of stimulated cells, was caused
      by manipulations to isolate cells that activated O2- production. Activity of
      mycotoxins was no dose-dependent permitting to consider their effect immunotoxic
      rather than immunomodulator; the absence of dose-dependence was connected to high
      variability of individual sensitivity to these compounds. Since the smaller
      concentrations by us used (10(-8) and 10(-6) mg/mL) are easily reachable in
      blood, it is important to point out the danger represented for immune system by
      mycotoxins also in very small quantities.

PMID- 19180807
TI  - Effect of naturally occurring isothiocyanates on the immune system.
AB  - Administration of allyl isothiocyanate (AITC) and phenyl isothiocyanate (PITC)
      was found to stimulate the immunological response in Balb/c mice. Treatment with
      five doses of AITC and PITC (25 microg/dose/animal, i.p.) was found to enhance
      the total WBC count (13,100 cells/mm3 for AITC) on 9th day and (10,316 cells/mm3
      for PITC) on 12th day respectively. Bone marrow cellularity (22.36 x 10(6)
      cells/femur for AITC, 21.3 x 10(6) cells/femur for PITC) as well as alpha
      esterase positive cell number also increased after treatment with AITC (1397
      cells/4000 cells) and PITC (1238 cells/4000 cells). Treatment with AITC and PITC
      along with the antigen sheep red blood cells (SRBC) produced an enhancement in
      the circulating antibody titer and the number of plaque forming cells (PFC) in
      the spleen. Maximum number of PFC (1329PFC/10(6) spleen cells) for AITC and PITC
      (1218PFC/10(6) spleen cells) was obtained on the 5th day. These results indicate
      the immunomodulatory activities of the two naturally occurring isothiocyanates
      namely, AITC and PITC.

PMID- 19180808
TI  - The influence of beta-glucan on immune responses in broiler chicks.
AB  - Beta-1,3/1,6-glucan (beta-glucan) was tested as a possible immunomodulator.
      Chicken macrophages from a macrophage cell line MQ-NCSU and from abdominal
      exudate of broiler chickens were exposed to various concentrations of beta-glucan
      in vitro. In addition, day-old broiler chicks were fed a diet containing 0, 20,
      and 40 mg/kg beta-glucan in the starter and 0, 20, and 20 mg/kg in the grower
      diet. Several baseline immune parameters were examined following such exposures.
      The results showed that beta-glucan exposure increased nitrite and interleukin-1
      (IL-1) production as well as induced macrophage to proliferate in culture.
      However, IL-6 production was not affected. Dietary beta-glucan supplementation
      increased the macrophage phagocytic activity, anti-sheep red blood cells antibody
      response post-boost, as well as the PHAP-mediated lymphoproliferative response
      measured as a toe-web swelling. The percentage of CD4+, CD8+, and CD4+/CD8+
      double positive lymphocytes in the intestinal intraepithelial leukocytes was
      increased in beta-glucan supplemented chicks. Furthermore, the primary and
      secondary lymphoid organs such as bursa of Fabricius, thymus and spleen were
      larger in beta-glucan-supplemented chicks as compared to the chicks on basal
      diet. The findings of these studies which showed that beta-glucan improves
      several baseline immune responses in the chicken imply that beta-glucan can be
      used as a possible immunomodulator in food animals such as the chicken.

PMID- 19180809
TI  - Immunological abnormalities in workers exposed to pollutants at an Egyptian
      copper company.
AB  - In the present work we studied: (a) biochemical changes; (b) serum
      immunoglobulins (IGs); and (c) mitogenecity of peripheral blood lymphocytes (PBL)
      in workers directly exposed to high concentrations of pollutants in several
      sectors of a major copper company in Alexandria. These sectors included the
      aluminum utensils refining of copper semicontinuous aluminum casting, brass
      foundries, and steel furnaces. Toxicants in these sectors included aluminum,
      hexachloroethan, silica, cadmium, copper, mercury, lead, abestos, nickels, zinc,
      silver, carbon iron, and sulfate present in high concentrations in the sectors
      where workers are directly exposed. Administrative personnel (indirectly exposed)
      were included as positive controls; negative controls were people living in areas
      of Alexandria where the concentrations of these toxicants are extremely low. All
      personnel of the aluminum utensils area showed reduction in serum levels of IgG,
      IgA, and IgM assayed by enzyme-linked immunosorbent assay (ELISA) while workers
      directly exposed in the other sectors showed elevated Igs. Mitogenic activity in
      cultured PBL assayed by 3H-thymidine uptake was impaired in all plant personnel.
      However, experimentals showed increases in the interleukins IL-2, IL-4, IL-6,
      interferon-gamma (IFN-gamma), tumour necrosis factor-alpha and-beta (TNF-alpha
      and beta) assayed by ELISA. Changes were directly related to duration of
      exposure. Some workers showed autoimmune symptoms such as arthritis and
      spondylitis. Allergic manifestations were also recorded. Thus, abnormalities were
      greatest in directly exposed workers, while other plant personnel showed some
      form of toxicity in the parameters studied. Clinical significance of the
      immunologic abnormalities seen is under further study.

PMID- 19180810
TI  - Dorsal cochlear nucleus projections to the inferior colliculus in the cat: a
      light and electron microscopic study.
AB  - In the present report retrograde and anterograde labeling techniques are used to
      study the projections of the dorsal cochlear nucleus (DCN) to the inferior
      colliculus in the cat. Horseradish peroxidase (HRP) or wheat germ agglutinin (WGA
      HRP) injections into the inferior colliculus produce large numbers of labeled
      neurons in the DCN on the opposite side. Labeled cells with projections to the
      colliculus are identified as fusiform and giant cells and are organized into
      rostrocaudal bands. The axons of these DCN neurons are labeled by anterograde
      transport of 3H-leucine and/or proline and studied in light and electron
      microscopic autoradiographs. Axons from the DCN terminate within the central
      nucleus of the inferior colliculus in densely labeled, rostrocaudally oriented
      bands. Less heavily labeled extensions of these bands are found in the deepest
      layer of the dorsal cortex, and light labeling is found adjacent to the bands in
      the central nucleus and in the ventrolateral nucleus. Cells in the dorsomedial
      DCN project to the most ventromedial part of the central nucleus while
      progressively more ventrolateral cells in the DCN project to more dorsolateral
      parts of the central nucleus. This present evidence suggests that the DCN sends
      afferents to only two of the four subdivisions of the central nucleus. Within
      these regions, the axons from the DCN form terminal boutons or boutons de passage
      characterized by medium-sized, round synaptic vesicles. The labeled endings
      nearly always make asymmetric synaptic contacts on the dendrites of disc-shaped
      and stellate cells in the central nucleus. A few axosomatic contacts are found on
      one particular cell type, possibly the stellate variety. The results support the
      hypothesis that each subdivision of the central nucleus receives afferents from a
      different set of cell types in the auditory nuclei of the lower brainstem. The
      banding patterns of the efferent cells in the cochlear nucleus and the axons
      within the central nucleus suggest that these inputs are congruent to the
      fibrodendritic layers of the central nucleus and may contribute to tonotopic
      organization in the central nucleus. Finally, the results suggest that each of
      the two major classes of cells in the central nucleus receives different patterns
      of inputs from the DCN. These morphological differences could contribute to
      different electrophysiological responses to the sound stimuli by these cells.

PMID- 19180811
TI  - Connections between the thalamus and the somatosensory areas of the anterior
      ectosylvian gyrus in the cat.
AB  - The thalamocortical and corticothalamic connections of the second somatic sensory
      area (SII) and adjacent cortical areas in the cat were studied with anterograde
      and retrograde tracers. Injections consisted of horseradish peroxidase conjugated
      to wheat germ agglutinin (HRP-WGA) or a mixture of equal parts of tritiated
      leucine and proline. The cortical regions to be injected were
      electrophysiologically studied with microelectrodes to determine the localization
      of the selected components of the body representation in SII. The distribution of
      recording points was correlated in each case with the extent of the injection
      mass in the cortex. Distributions of retrograde and anterograde labeling in the
      thalamus were reconstructed from serial coronal sections. The results from cases
      with injections of tracers exclusively confined to separate parts of the body map
      in SII indicated a fairly precise topographical organization of projections from
      the ventrobasal complex (VB) to SII. The labeled cells and fibers were located
      within a series of lamella-like rods that curved throughout the dorsoventral and
      rostrocaudal axis of VB. The position and extent of these lamellae shifted from
      medial and ventral, in the medial subdivision of ventral posterior lateral
      nucleus (VPLm) for radial forelimb digit zones of SII, to dorsal, posterior, and
      lateral, in the lateral subdivision of ventral posterior lateral nucleus (VPL1)
      for proximal leg and trunk regions in SII. For every injected area in SII the
      densest clustering of labeled cells and fibers was usually more posteriorly
      represented in VB. The distribution in these dense zones of labeling often
      extended through the central core of VB. SII projecting neurons were also
      consistently noted in the extreme rostral portion of the medial subdivision of
      the posterior nuclei (Pom) that lies dorsal to VB. Corticothalamic and
      thalamocortical connections for SII were entirely reciprocal. Injections of
      tracers into cortical areas surrounding SII labeled other parts of the posterior
      complex but failed to label any part of VB except when the injection mass also
      diffused into SII. Injections into the somatic sensory cortex located lateral to
      SII, within the lips and depth of the upper bank of the anterior ectosylvian
      sulcus (AES), heavily labeled the central and posterior portions of Pom.
      Substantial labeling was noted in the lateral (Pol) and intermediate (Poi)
      divisions of Po only when the injections involved some part of the auditory areas
      located immediately posterior to SII. This region included the anterior auditory
      area that occupies the most posterior part of the AEG and both banks of the
      immediately adjoining AES. The magnocellular nucleus of the medial geniculate
      (MGmc) was labeled only when some part of the auditory cortex was injected. The
      suprageniculate nucleus (SG) was labeled from the insula and lower bank of the
      AES. These results indicated that the medial (rostral and caudal Pom) and lateral
      components (Poi, Pol, MGmc) of the posterior complex have separate cortical
      projection zones to somatic sensory and auditory cortical regions, respectively.
      SIV and the lateral extent of area 5a located in the medial bank of the anterior
      suprasylvian sulcus sent projections to the deep layers of the superior
      colliculus and the ventrolateral periaqueductal gray. No cortico-tectal
      projections were seen from SII.

PMID- 19180812
TI  - Subcortical projections of the inferior parietal cortex (area 7) in the stump
      tailed monkey.
AB  - The efferent projections of the neocortex on the lateral convexity of the
      inferior parietal lobe (area 7 of Brodmann) were examined using the anterograde
      transport of tritiated amino acids. Multiple injections of 3H-leucine and 3H
      proline were placed within the three cytoarchitecturally distinct zones that lie
      along the exposed surface of the inferior parietal lobe (IPL). The subcortical
      projections resulting from these injections were studied. Prominent projections
      were seen in the thalamus (medial and lateral pulvinar), brainstem (dorsolateral
      and ventral pontine nuclei), and basal ganglia (caudate and putamen) with less
      dense label over the thalamic intralaminar nuclei, pretectal complex, superior
      colliculus, reticular nucleus of the thalamus, suprageniculate nucleus, lateral
      posterior nucleus, oral pulvinar, and claustrum. In many of these cases there was
      a topographical relationship apparent with regard to the injections placed along
      the rostral-caudal dimension of the IPL. There is a striking reciprocal
      arrangement in the afferent and efferent projection systems of the IPL. The
      functional relevance of both the topography and the efferent projections of the
      IPL is discussed.

PMID- 19180813
TI  - The development of retinal ganglion cells in a tetraploid strain of Xenopus
      laevis: a morphological study utilizing intracellular dye injection.
AB  - The morphological development of retinal ganglion cells was examined in a
      tetraploid strain of Xenopus frogs. The enlarged cells of the tetraploid strain
      facilitate the application of intracellular techniques. Using an in vitro retinal
      preparation and Nomarski optics, intracellular recording and dye injection were
      carried out under visual control on ganglion cells in central retina from 2 days
      of development (stage 24) to metamorphosis (stage 64). We identified three phases
      in the morphological differentiation of ganglion cells. During the first phase
      (stages 24-30), all cells were neuroepitheliallike in form and possessed robust
      resting potentials in the range of -35 to -60 mV, and dye-coupling was
      occasionally observed between neighboring cells. During the second phase of
      ganglion cell development (stages 31-45) the neurons had begun to elaborate axons
      and dendrites. These cells possessing neurites had resting potentials between -15
      and -30 mV, and no dye-coupling was observed between neighbors. During the third
      and final phase of maturation, from stage 46 onward, three distinct morphological
      types of ganglion cells could be identified. Type I cells had the smallest somata
      and the smallest-diameter dendritic arborizations. The profusely branched
      dendrites of these cells ramify extensively throughout the inner plexiform layer.
      Type II cells had large somata, intermediate-diameter dendritic fields, and a
      highly elaborate dendritic branching pattern. These cells were seen to arborize
      within two sublamina in the inner plexiform layer. Type III cells had large
      somata, the largest-diameter dendritic fields, and a dendritic arbor with long
      primary branches but little higher-order branching. These large dendritic fields
      were confined to a single sublamina of the inner plexiform layer, abutting the
      inner nuclear layer. While most phase 3 cells showed radial axon trajectories
      from the soma to the optic disc, a minority of cells (1-5%) with erratic and
      nonradial axon trajectories were also observed. Our data provide a morphological
      description of ganglion cell maturation in the central retina of Xenopus. We show
      that very early in development (as early as stage 46) three distinct
      morphological types of retinal ganglion cells are present, which correspond to
      the three classes of ganglion cells previously described in adult Xenopus (Chung
      et al., '75).

PMID- 19180814
TI  - Motoneuron death after sciatic nerve section in newborn rats.
AB  - When the sciatic nerve was cut in newborn rats almost all of the motoneurons were
      subsequently lost. The adult sciatic nerve contained 7,640 myelinated fibres of
      which 1,650 were motor axons. The ventral roots of the sciatic nerve (L4-L6)
      contained in all 4,080 myelinated fibres; only 2,380 were present 5-30 weeks
      after the sciatic nerve had been cut at birth. The deficit of 1,700 fibres
      corresponded to the number of motor axons in the sciatic nerve. The motoneuron
      pools were depleted and practically no labelled or unlabelled perikarya were
      found after HRP had been applied to the nerve proximal to the former lesion. The
      deficit of ventral root fibres was 1,030 when the nerve had been cut at age 1
      week; nerve section 4 weeks after birth was not followed by retrograde loss of
      motor axons. Nerve crush at birth caused a deficit of 1,230 ventral root fibres.
      The incomplete loss of motor axons after crushing was due to the fact that not
      all axons had been severed. The continuity of the nerves cut at birth was always
      restored and myelinated axons which probably were dorsal root ganglion afferents
      grew into the atrophic muscles. Roughly two-thirds of the myelinated sensory
      fibres degenerated after axotomy at birth. The denervated muscle fibres were not
      reinnervated but vanished eventually and were replaced by fat cells.

PMID- 19180815
TI  - Regional (14C) 2-deoxyglucose uptake during forelimb movements evoked by rat
      motor cortex stimulation: cortex, diencephalon, midbrain.
AB  - The caudal forelimb region of right "motor" cortex was repetitively stimulated in
      normal, conscious rats. Left forelimb movements were produced and (14C) 2
      deoxyglucose (2DG) was injected. After sacrifice, regions of increased brain
      (14C) 2DG uptake were mapped autoradiographically. Uptake of 2DG increased about
      the stimulating electrode in motor (MI) cortex. Columnar activation of primary
      (SI) and second (SII) somatosensory neocortex occurred. The rostral or second
      forelimb (MII) region of motor cortex was activated. Many ipsilateral subcortical
      structures were also activated during forelimb MI stimulation (FLMIS). Rostral
      dorsolateral caudate-putamen (CP), central globus pallidus (GP), posterior
      entopeduncular nucleus (EPN), subthalamic nucleus (STN), zona incerta (ZI), and
      caudal, ventrolateral substantia nigra pars reticulata (SNr) were activated.
      Thalamic nuclei that increased (14C) 2DG uptake included anterior dorsolateral
      reticular (R), ventral and central ventrolateral (VL), lateral ventromedial (VM),
      ventral ventrobasal (VB), dorsolateral posteromedial (POm), and the
      parafascicular-centre median (Pf-CM) complex. Activated midbrain regions included
      ventromedial magnocellular red nucleus (RNm), posterior deep layers of the
      superior colliculus (SCsgp), lateral deep mesencephalic nucleus (DMN), nucleus
      tegmenti pedunculopontinus (NTPP), and anterior pretectal nucleus (NCU).
      Monosynaptic connections from MI or SI to SII, MII, CP, STN, ZI, R, VL, VM, VB,
      POm, Pf-CM, RNm, SCsgp, SNr, and DMN can account for ipsilateral activation of
      these structures. GP and EPN must be activated polysynaptically, either from MI
      stimulation or sensory feedback, since there are no known monosynaptic
      connections from MI and SI to these structures. Most rat brain motor-sensory
      structures are somatotopically organized. However, the same regions of R, EPN, CM
      Pf, DMN, and ZI are activated during FLMIS compared to VMIS (vibrissae MI
      stimulation). Since these structures are not somatopically organized, this
      suggests they are involved in motor-sensory processing independent of which body
      part is moving. VB, SII, and MII are activated during FLMIS but not during VMIS.

PMID- 19180816
TI  - Regional (14C) 2-deoxyglucose uptake during forelimb movements evoked by rat
      motor cortex stimulation: pons, cerebellum, medulla, spinal cord, muscle.
AB  - Electrical stimulation of the right forelimb motor (MI) sensory (SI) cortex in
      normal, adult rats produced repetitive left forelimb movements. Regions of
      increased (14C) 2-deoxyglucose (2DG) uptake were mapped auto-radiographically
      during these movements. MI stimulation activated the ipsilateral reticular
      tegmental pontine nucleus (RTP) and the middle (rostral-caudal) third of the
      pontine nuclei including pyramidal (P), medial (POM), ventral (POV), and lateral
      (POL) pontine nuclei. The ipsilateral inferior olivary complex was activated
      including dorsal accessory olive (DAO), principal olive (PO), and medial
      accessory olive (MAO). The contralateral lateral reticular (LR) nucleus and
      nucleus cuneatus (CU) were activated. Lateral vermal, paravermal, and hemispheric
      portions of the contralateral cerebellum were also activated. Parts of vermian
      lobules IV, V, VI, VII, and VIII, and lobulus simplex, crus I, crus II,
      paramedian lobule, and copula pyramidis were activated. Granule cell layers were
      activated much more than molecular layers. Discrete microzones of high granule
      cell 2DG uptake alternated with zones of low uptake in left paramedian lobule and
      copula pyramidis and may correlate with the fractured cerebellar somatotopy
      described physiologically by Welker and his associates. Portions of the left
      lateral and interpositus nuclei were metabolically activated. Medial portions of
      laminae I-VI were activated in the dorsal horn of cervical spinal cord. The 2DG
      uptake was either unchanged or decreased in the ventral horn. Thoracic and lumbar
      spinal cord were not activated. Monsynaptic MI and SI connections to P, POM, POV,
      POL, RTP, DAO, PO, MAO, LR, CU, and spinal cord could account for activation of
      those structures. However, there are no direct MI or SI connections to the deep
      cerebellar nuclei, the cerebellar hemisphere, or the muscles. Activation of these
      structures must be due to activation of polysynaptic pathways, sensory feedback
      from the moving forelimb, or both. The present experiments cannot distinguish
      these possibilities. Comparison of the regions activated during forelimb MI
      stimulation (FLMIS) to those activated during vibrissae MI stimulation (VMIS)
      suggests that the pontine nuclei, cerebellar hemisphere, and possibly the deep
      cerebellar nuclei are somatotopically organized. RTP, LR, CU, and spinal cord
      were activated during FLMIS but were not activated during VMIS. The failure to
      activate the ventral horn of cervical spinal cord may be due to known inhibition
      of alpha-motor neurons during motor cortex stimulation.

PMID- 19180817
TI  - The patient with special needs.

PMID- 19180818
TI  - Bacteria can hide out in cells for weeks.

PMID- 19180819
TI  - Treatment testing of waterlines.

PMID- 19180820
TI  - Investing in your instruments.

PMID- 19180821
TI  - Creating a successful infection control program.

PMID- 19180822
TI  - Document defensively: here's how.

PMID- 19180823
TI  - New ADA workforce model: Community Dental Health Coordinator.

PMID- 19180824
TI  - Managing your stress at work.

PMID- 19180825
TI  - [Image of the month. Distal femur myofibrosarcoma ].

PMID- 19180826
TI  - [How I treat... some skin disorders from the angle of innate immunity].
AB  - Innate immunity represents a complex biological organization exhibiting some
      implications in diverse disorders, in particular at the level of the skin. Its
      functioning relies on two main groups of components encompassing the PRRs
      (Protein Recognition Receptors) and the antimicrobial peptides. In humans,
      particularly in the skin, the major PRRs are represented by the Toll-like
      receptors (TLRs). The main antimicrobial peptides encompass the alpha- and beta
      defensins, and cathelicidins. The expression of the innate immunity compounds is
      modulated by some drugs. This feature represents a mode of action that remained
      ignored in the past.

PMID- 19180828
TI  - [Cardiac sarcoidosis: a case report].
AB  - Sarcoidosis is a systemic disease of unknown aetiology characterised by the
      formation of non caseating epithelioid cell granuloma, which can occur in
      virtually any organ. The involvement of the heart is an important prognostic
      factor in sarcoidosis. Early treatment prevents irreversible damage of the heart
      and seems to be associated with better prognosis.

PMID- 19180827
TI  - [Invasive pulmonary mucormycosis with invasion of the thoracic spine in a patient
      with myelodysplastic syndrome].
AB  - We report the case of a 67-year-old patient who presented with a myelodysplastic
      syndrome and who developed a pulmonary mucormycosis with a rare extension to the
      dorsal spine. A decompressive laminectomy was attempted after failure of broad
      spectrum antifungal treatment (Cancidas, V-Fend). The diagnosis was obtained
      after surgical biopsy. The scheduled lobectomy could not be performed because of
      altered clinical condition. The patient eventually died despite adapted
      antifungal treatment (Abelcet, Posaconazole). Pulmonary mucormycosis is a rare
      cause of mycotic infection that reaches most of the time immunocompromised
      patients. The pathogenic agent is part of zygomyces that have angio-invasive
      ability. Perineural propagation was recently described. Immunodepression, late
      diagnosis and lack of response to new generation antifungal drugs (V-Fend,
      Cancidas) are responsible for therapeutic failure in this disease. This case
      emphasizes the risk inherent to empirical antifungal treatment and the need of
      early biopsy in cases that do not respond to treatment.

PMID- 19180829
TI  - [First-line dermatologic emergencies].
AB  - Dermatological emergencies encompass a series of distinct diseases of infectious,
      autoimmune and environmental origins. They account for a number of consultations
      at the general practitioner's office and in emergency units of medical centers.
      The concerned first line medical staffs are then facing some conditions with a
      dramatic potential. We review the most common conditions including urticaria,
      angioedema, infectious cellulitis, acute photodermatoses, the Lyell syndrome,
      some other paroxysmal severe adverse drug reactions, burns, erythroderma and the
      Kaposi-Juliusberg varicelliform eruption.

PMID- 19180830
TI  - [Swallowing disorders in the elderly: an underestimated problem].
AB  - Swallowing disorders are frequently observed in the elderly and often accompany
      an organic pathology. Such disorders may quickly constitute a threat for life:
      inhalation syndrome, pulmonary infection, undernutrition, dehydration. Diagnosing
      swallowing disorders is difficult and relies on anamnesis, clinical examination
      combined with paraclinical investigations. However, there is little place for
      medicinal or surgical treatment, their management being integral and
      multidisciplinary.

PMID- 19180831
TI  - [Is it possible to integrate frailty of old person, in surgical procedure?].
AB  - Frailty in the elderly is an important factor of morbidity, particularly in the
      setting of surgery. The various pathologies that can lead to a functional decline
      are well known. The risk of mortality and morbidity should be assessed as a
      function of the nature of the surgical procedure and of the disease for which it
      is required; the factors of severity, the predictable duration of the procedure,
      and the expected blood losses must also be taken into account. The thrombo
      embolic risk should finally be considered. In the elderly, one may say that the
      functional risk matters more than the vital risk. Frailty must be integrated into
      the risk assessment; however, further studies are needed to better determine the
      impact of that new concept. Undoubtedly, the cognitive and nutritional status are
      of main importance. A better knowledge of the risks should lead to validate
      specific interventions that could help to prevent surgical complications, shorten
      the length of hospital stay, and protect the self-sufficiency of the aged.

PMID- 19180832
TI  - [About the discovery of a hepatic subcapsular collection as early complication of
      transperitoneal laparoscopy. Review of the clinical implications based on the
      hepatic capsular and retroperitoneal anatomy, its subdivisions and
      communications].
AB  - We report a case of hepatic subcapsular collection as early complication of
      transperitoneal laparoscopy. The etiology seems to be a detachment of the hepatic
      capsule induced by laparoscopic gas. We discuss the anatomic data about the liver
      capsule, renal fascia and retroperitoneal subdivisions supporting such a
      mechanism.

PMID- 19180833
TI  - [Abdominal actinomycosis: four cases].
AB  - The abdominal actinomycosis (AA) is a rare and often unrecognised suppurative
      chronic illness. It is caused by an anaerobic Gram positive bacteria, Actinomyces
      israelii. Abdominal actinomycosis is responsible for pseudotumoral syndrome often
      leading, to a large and mutilating surgery whereas a prolonged treatment by
      antibiotics would have permitted to cure the disease. The diagnosis is obtained
      generally from anatomopathologic exam. We report four cases of abdominal
      actinomycosis being revealed by a pseudotumoral syndrome. The diagnosis was only
      made after surgery. In spite of an active treatment by antibiotics during several
      months, two of our patients had a relapse of the infectious process. These four
      observations confirm the diagnostic and therapeutic difficulties previously
      reported by other authors.

PMID- 19180834
TI  - [Predictive value of antenatal ultrasound for the neonatal diagnostic of renal
      and ureteral anomaly].
AB  - Pyelectasis is a dilatation of the renal pelvis. It must be differentiated from
      hydronephrosis which is a dilation of the renal pelvis and of the renal calyces.
      In this retrospective study, we focused on the treatment and follow up of 31
      newborns in whom a pyelectasis had been diagnosed in utero. At the end of the
      study, 20 babies showed no sign of an urologic disorder whereas 11 babies did.
      Our study suggests that it is crucial to search for an urologic disorder in the
      neonatal period when a fetal pyelectasis has been diagnosed.

PMID- 19180835
TI  - [Sacroilitis and osteomyelitis of the humeral bone du to Brucella melitensis in
      an adolescent].
AB  - We describe a case of a 10 year old patient who presented with intermittent fever
      and pain in the pelvis and elbow region. From the history, imaging and laboratory
      tests, a diagnosis of Brucella sacroiliitis and elbow osteoarthritis was made.
      The patient was given an antibiotic treatment for 3 months with a progressive
      improvement of symptoms to complete recovery, and normalization of imaging and
      laboratory findings.

PMID- 19180836
TI  - [Fast installation of blepharochalasis].
AB  - Blepharochalasis is characterized by recurrent painless oedema of the eyelids
      leading to alteration of periorbital skin with a nearly complete loss of elastic
      fibers. It usually affects the upper eyelids bilaterally. An 11-year-old girl
      suffered from recurrent erythematous swelling episodes during 3 months. The
      manifestations were confined to the periorbital region. She gradually noticed a
      bilateral loss of elasticity of the skin of the upper eyelid. The skin showed
      some folding and laxity. A mild aponeurotic ptosis was present. A skin biopsy
      showed the absence of elastic fibres. Blepharochalasis is a disease of young
      people. It has been divided in two hypertrophic and atrophic types. The condition
      typically follows recurrent painless episodes of oedema infiltrating both upper
      eyelids. The eyelid oedema usually resolves after several days and recures
      several times a year.

PMID- 19180838
TI  - Ethics and pandemic planning.

PMID- 19180837
TI  - [JUPITER: reduction by rosuvastatin of cardiovascular events and mortality in
      healthy subjects without hyperlipidaemia but with elevated C-reactive protein].
AB  - High levels of high-sensitivity C-reactive protein (hs-CRP) are an independent
      cardiovascular marker, which may be reduced by statin therapy. JUPITER is a
      randomised clinical trial that compares the effects of rosuvastatin 20 mg (n =
      8901) and placebo (n = 8901) in apparently healthy individuals, without
      hyperlipidaemia (LDL < 130 mg/dl; median 108 mg/dl), but with moderately elevated
      hs-CRP levels (> 2 mg/l; median 4.25 mg/l). Rosuvastatin reduced LDL cholesterol
      by 50% (to a median of 55 mg/dl) and hs-CRP by 37%. The trial, which should last
      5 years, was stopped after a median follow-up of 1.9 years because of an
      imbalance in favour of the rosuvastatin group. Indeed, when compared to placebo,
      rosuvastatin was associated with a relative risk reduction in the composite
      primary end point of 44%, in myocardial infarction of 54%, in stroke of 48%, in
      revascularization procedures or hospitalisations for unstable angina of 47%, in
      major cardiovascular events (myocardial infarction, stroke and death) of 47% and
      in deaths from any cause of 20%. Consistent effects were observed in all
      subgroups evaluated. The only adverse event was a higher incidence of physician
      reported diabetes in the rosuvastatin group compared to the placebo group. This
      study demonstrates that rosuvastatin 20 mg reduces the incidence of
      cardiovascular events, including total mortality, in apparently healthy persons
      without hyperlipidaemia, but with elevated hs-CRP. However, the design of the
      trial does not allow discriminating which part of the favourable effect results
      from the drastic reduction in LDL cholesterol and which part results from the
      reduction in hs-CRP stricto sensu.

PMID- 19180840
TI  - Happiness at work.

PMID- 19180839
TI  - TNA President's annual convention address.

PMID- 19180841
TI  - TNA members develop legislative strategies for next general assembly.

PMID- 19180842
TI  - Anatomic problems of the colon.

PMID- 19180843
TI  - Appendicitis.

PMID- 19180844
TI  - Bacteria and foodborne illness.

PMID- 19180845
TI  - Celiac disease.

PMID- 19180846
TI  - Barrett's esophagus.

PMID- 19180847
TI  - Heartburn, gastroesophageal reflux (GER), and gastroesophageal reflux disease
      (GERD).

PMID- 19180848
TI  - Panniculectomy: what the LP/VN needs to know.

PMID- 19180849
TI  - Investigation of outbreak of infections caused by Salmonella Agona.

PMID- 19180850
TI  - Ulcerative colitis.

PMID- 19180851
TI  - Cerebral white-matter lesions in asymptomatic military divers.
AB  - INTRODUCTION: There is some concern that over a period of years, diving may
      produce cumulative neurological injury even in divers who have no history of
      decompression sickness. We evaluated asymptomatic divers and controls for
      cerebral white-matter lesions using magnetic resonance imaging (MRI). METHODS:
      The study enrolled 113 male military divers (34.4 +/- 5.6 yr) and 65 non-diving
      men (33.1 +/- 9.0 yr) in good health. Exclusion criteria included any condition
      that might be expected to produce neurological effects. Patent foramen ovale was
      not assessed. A questionnaire was used to elicit diving history. A 1.5-T MRI
      device was used to acquire T1, T2-weighted, and fluid attenuated inversion
      recovery (FLAIR) images of the brain. A lesion was counted if it appeared
      hyperintense on both T2-weighted and FLAIR images. RESULTS: MRI revealed brain
      lesions in 26 of 113 divers (23%) and in 7 of 65 (11%) controls, a difference
      that was statistically significant. There was no significant difference between
      the groups with respect to blood pressure, smoking history, or alcohol
      consumption, and no subject reported a history of head trauma or migraine. There
      was no relationship between MRI findings and age, diving history, or lipid
      profile in divers. DISCUSSION: The higher incidence of lesions in the cerebral
      white matter of divers confirms the possibility that cumulative, subclinical
      injury to the neurological system may affect the long-term health of military and
      recreational divers.

PMID- 19180852
TI  - Self-rotations in simulated microgravity: performance effects of strategy
      training.
AB  - INTRODUCTION: This research studies reorientation methodologies in a simulated
      microgravity environment using an experimental framework to reduce astronaut
      adaptation time and provide for a safety countermeasure during extravehicular
      activity. METHODS: There were 20 subjects (10 men, 10 women, mean age of 23.6 +/-
      3.5) who were divided into 2 groups, fully trained and minimally trained, which
      determined the amount of motion strategy training received. Subjects performed a
      total of 48 rotations about their pitch, roll, and yaw axes in a suspension
      system that simulated microgravity. In each trial subjects either rotated 90
      degrees in pitch, 90 degrees in roll, or 180 degrees in yaw. Experimental
      measures include subject coordination, performance time, cognitive workload
      assessments, and qualitative motion control strategies. RESULTS: Subjects in the
      fully trained group had better initial performance with respect to performance
      time and workload scores for the pitch and yaw rotations. Further, trained
      subjects reached a steady-state performance time in fewer trials than those with
      minimal training. The subjects with minimal training tended to use motions that
      were common in an Earth environment since no technique was provided. For roll
      rotations they developed motions that would have led to significant off-axis
      (pitch and yaw) rotations in a true microgravity environment. CONCLUSIONS: We
      have shown that certain body axes are easier to rotate about than others and that
      fully trained subjects had an easier time performing the body rotations than the
      minimally trained subjects. This study has provided the groundwork for the
      development of an astronaut motion-control training program.

PMID- 19180853
TI  - Bubble formation and endothelial function before and after 3 months of dive
      training.
AB  - INTRODUCTION: It has been suggested that repeated compression-decompression
      cycles reduce diver susceptibility to decompression sickness (DCS). This study
      examined whether intensive scuba dive training would reduce bubble formation and
      modulate endothelial function as shown by skin circulation. METHODS: There were
      22 military divers who were studied before and after a 90-d program of physical
      training and open-sea air diving (mean 67 dives total). Skin blood flow in the
      forearm was measured at rest (baseline), during post-occlusive hyperemia
      (endothelium-dependent vasodilatation), and with local heating to 42 degrees C
      (maximal vasodilatation). Subjects were also examined by pulsed Doppler for
      venous bubbles 30, 60, and 90 min after surfacing from a hyperbaric exposure to
      400 kPa (30 msw) for 30 min in a dry chamber. RESULTS: None of the divers
      experienced DCS during the training period. There was no change in weight, body
      mass index, maximal oxygen uptake, or endothelial function. Bubble grades by the
      Kisman Integrated Severity Score were significantly decreased immediately after
      the diving training period (3.6 +/- 9.2 vs. 16.4 +/- 14.3) and increased 3 mo
      after this period (10.3 +/- 13.9 vs. 3.6 +/- 9.2). DISCUSSION: The results
      highlight that repeated scuba dives and regular physical exercise activity reduce
      bubble formation and probably have a protective effect against DCS risk. Although
      this phenomenon has been observed for decades, the mechanism remains complex and
      the results cannot elucidate the effects of physical exercise and NO production.
      Bubble formation could activate the stress response which could be the basis for
      diving acclimatization.

PMID- 19180854
TI  - Vestibular function in military pilots before and after 10 s at +9 Gz on a
      centrifuge.
AB  - BACKGROUND: Effects of high Gz acceleration can threaten flight safety through
      loss of consciousness or a lesser-known phenomenon, G-induced vestibular
      dysfunction (GIVD). There are reports of GIVD following high-G flight or
      centrifuge exposure. The aim of this study was to explore this problem under
      controlled conditions using a human centrifuge. METHODS: There were 11 pilots who
      were exposed to +9 Gz for 10 s. Measurements were made before and after G
      exposure to assess vestibular function, including spontaneous nystagmus,
      positioning nystagmus, optokinetic nystagmus, vestibular ocular reflex,
      vestibular-vision interaction, subjective vision vertical perception, and
      vestibular-evoked myogenic potentials. RESULTS: No significant change was found
      for vestibular function after the Gz exposure. CONCLUSION: It appears +9 Gz for
      10 s does not produce GIVD. However, the possible effects of prolonged high G
      maneuvers in modern aircraft combined with head movements may warrant further
      study.

PMID- 19180855
TI  - Seating type and cognitive performance after 3 hours travel by high-speed boat in
      sea states 2-3.
AB  - INTRODUCTION: Transit in high-speed marine craft subjects occupants to a rough
      ride as the boat impacts the waves. This induces high levels of physical stress,
      which may inhibit cognitive performance during military operations and life
      saving activities. Land-based research suggests that suspension seats reduce
      vibration and, therefore, stress. We hypothesized that subjects using suspension
      seats would demonstrate better cognitive performance, lower perceptions of
      exertion, fatigue, and sleepiness, and lower salivary concentrations of cortisol
      than those using fixed seats. METHODS: Subjects, naval personnel, were divided
      into fixed (N = 6) and suspension seat (N = 6) groups. Subjects undertook forward
      and backward number recall and random number generation tests pre- and post
      transit (3 h in sea states 2-3). Salivary cortisol concentrations were sampled
      pre- (1100 h) and post-transit (1700 h) and at the same times on a control day.
      Post-transit perceptions of exertion, fatigue, and sleepiness were measured
      subjectively. RESULTS: The suspension seat group demonstrated better performance
      post-transit than the fixed seat group for forward number recall and showed a
      significant pre- to post-transit improvement in backward number recall. The
      suspension seat group reported less fatigue and sleepiness. The suspension seat
      group had significantly higher salivary cortisol concentrations than the fixed
      seat group post-transit. Regression analyses found a quadratic correlation
      between delta cortisol concentrations and delta random number generation scores
      (R2 = 0.68). DISCUSSION: Results show that the use of suspension seats during
      transit in high-speed marine craft may be advantageous with regard to cognitive
      performance.

PMID- 19180857
TI  - Understanding vestibular function in changing gravity environments.

PMID- 19180858
TI  - Space technologies used to improve health care in remote areas.

PMID- 19180856
TI  - Fatigue countermeasures in aviation.
AB  - Pilot fatigue is a significant problem in modern aviation operations, largely
      because of the unpredictable work hours, long duty periods, circadian
      disruptions, and insufficient sleep that are commonplace in both civilian and
      military flight operations. The full impact of fatigue is often underappreciated,
      but many of its deleterious effects have long been known. Compared to people who
      are well-rested, people who are sleep deprived think and move more slowly, make
      more mistakes, and have memory difficulties. These negative effects may and do
      lead to aviation errors and accidents. In the 1930s, flight time limitations,
      suggested layover durations, and aircrew sleep recommendations were developed in
      an attempt to mitigate aircrew fatigue. Unfortunately, there have been few
      changes to aircrew scheduling provisions and flight time limitations since the
      time they were first introduced, despite evidence that updates are needed.
      Although the scientific understanding of fatigue, sleep, shift work, and
      circadian physiology has advanced significantly over the past several decades,
      current regulations and industry practices have in large part failed to
      adequately incorporate the new knowledge. Thus, the problem of pilot fatigue has
      steadily increased along with fatigue-related concerns over air safety. Accident
      statistics, reports from pilots themselves, and operational flight studies all
      show that fatigue is a growing concern within aviation operations. This position
      paper reviews the relevant scientific literature, summarizes applicable U.S.
      civilian and military flight regulations, evaluates various in-flight and pre
      /postflight fatigue countermeasures, and describes emerging technologies for
      detecting and countering fatigue. Following the discussion of each major issue,
      position statements address ways to deal with fatigue in specific contexts with
      the goal of using current scientific knowledge to update policy and provide tools
      and techniques for improving air safety.

PMID- 19180859
TI  - Taking on the nurse faculty shortage. The role of colleges and universities.

PMID- 19180861
TI  - APNs and prescription writing.

PMID- 19180862
TI  - The f(-) word.

PMID- 19180863
TI  - Collaboration, vision and reality: water fluoridation in New Zealand (1952-1968).
AB  - In comparison with that of other nations in the British Commonwealth, New
      Zealand's early and comparatively high adoption of water fluoridation was a
      distinctive health policy. National concerns about the caries epidemic and the
      legacies of TR Hunter, F Truby King, HP Pickerill and JP Walsh engendered a
      spirit of cooperation between the Department of Health, the New Zealand School
      Dental Service, the Medical Research Council (of New Zealand), the New Zealand
      Dental Association and the University of Otago's dental and medical schools. The
      consequence was a contagious culture of multidisciplinary research and
      institutional liaisons that produced exceptional dental epidemiology. The
      government's involvement in children's public dentistry harmonised with fluoride
      advocates' radical vision of community caries reduction. New Zealand assumed not
      only a leading international role in immediate post-World War cariology, but also
      the dominant position in the fluoride politics of the British Commonwealth. The
      incomplete fulfilment of Fuller's "Dreams Pursued" presents a case study that
      confirms the roles of both scientific evidence and centralised political
      authority in public health administration. Paradoxically, political scientists
      have largely ignored New Zealand's early adoption of water fluoridation. This
      paper addresses this deficiency.

PMID- 19180864
TI  - The Northland fluoridation advocacy programme: an evaluation.
AB  - On 20 July 2006, the Far North District Council resolved to fluoridate Kaitaia
      and Kaikohe. This was the first such initiative by any Territorial Local
      Authority (TLA) in New Zealand for 23 years, and resulted from a fluoridation
      advocacy programme. This paper describes the programme implementation, assesses
      its consistency with the principles of the Treaty of Waitangi, and critically
      examines the collaboration between the fluoride advocate and the key
      stakeholders. Process evaluation identified three main categories of programme
      implementation: policy advocacy, community action projects, and media advocacy.
      The collaboration of iwi, Maori health providers and the community suggests that
      the programme was consistent with the principles (partnership, participation and
      protection) ofthe Treaty ofWaitangi. Media advocacy played an important role in
      reflecting and engaging community views on fluoridation, and it influenced
      decision-making by the Far North District Council. The simultaneous, combined
      'top-down and bottom-up' approach was an effective and successful strategy for
      fluoridation advocacy in the community. Less integrated approaches implemented on
      their own (such as the 'top down' approach in Whangarei and the 'bottom-up'
      approach in Dargaville) were not effective.

PMID- 19180866
TI  - Te waiora, the water of life.

PMID- 19180865
TI  - Dispatches from the front-line: an analysis of fluoridation campaigns in southern
      New Zealand, 2002-2006.
AB  - OBJECTIVES: The paper aims to analyse recent campaigns for water fluoridation in
      the South Island and to identify lessons to be learned from the outcomes. DESIGN:
      The research uses a systematic case study analysis based on a public policy
      framework, drawing on key informants, public documents and participant
      observation of campaigns in five separate communities. RESULTS: Over a four-year
      period in five specific communities (Gore and Southland in 2004; Ashburton in
      2002 and 2006; and Grey and Westland in 2005), the opportunity to introduce or
      retain fluoridation was rejected by local Councils. The extent of community
      understanding of the issues, the processes of engagement on the part of the
      health systems and the approaches to decision-making by Councils varied widely,
      but the main inputs to decisions were the rejection of expert health advice and a
      reliance on binding referenda or other assessments of the strength of community
      feeling. CONCLUSION: More evidence-based decision-making on fluoridation is
      required. Options at local level include tribunals and other mechanisms to
      support Councils, but it is likely that stronger national policy leadership and
      the application of robust health impact assessment may be necessary to ensure
      improved oral health and the reduction of inequalities.

PMID- 19180867
TI  - Prevalence of enamel defects and dental caries among 9-year-old Auckland
      children.
AB  - OBJECTIVES: To report the prevalence and severity of enamel defects and dental
      caries in a probability-based sample of 9-year-old children in the Auckland
      region, both overall and by residence in fluoridated and non-fluoridated areas.
      DESIGN: A two-stage clustered design with stratification. Strata were defined by
      fluoridated and non-fluoridated regions, school size, and school decile status.
      SETTING: Invitations, consent forms and questionnaires were distributed to
      eligible participants at school for completion at home. Participants were
      examined at school-based clinics or in a mobile clinic. PARTICIPANTS/MATERIALS
      AND METHODS: The source population was 9-year-old children attending schools in
      the Auckland region and enrolled with the Auckland Regional School Dental
      Service. Participants returned a completed consent form and questionnaire by post
      and then had a dental examination. Regression analyses accommodating probability
      sampling weights, stratification and clustering were employed. MAIN OUTCOME
      MEASURES: The modified Developmental Defects of Enamel index was used to classify
      enamel defects in permanent teeth. Diagnosis of dental caries on deciduous and
      permanent teeth was visually-based. RESULTS: Overall, 612 children participated,
      310 in fluoridated and 302 in non-fluoridated areas. Diffuse opacities are
      prevalent inAuckland, with 28.0 per 100 children affected. Significant regional
      differences by fluoridation status were apparent, with diffuse opacity rates of
      29.1 per 100 and 14.7 per 100 children in fluoridated and in non-fluoridated
      areas respectively (P<0.001). Conversely, the prevalence of deciduous teeth
      dental caries was significantly lower in fluoridated areas (54.9 per 100) than in
      non-fluoridated areas (62.0 per 100), P=0.05. CONCLUSIONS: Diffuse opacities were
      the predominant tooth defect found in this study, but their prevalence appears
      largely unchanged from estimates reported within New Zealand over the last 25
      years.

PMID- 19180868
TI  - Most cited: Number 3. Defects of tooth enamel in children in fluoridated and non
      fluoridated water areas of the Auckland region.

PMID- 19180869
TI  - New Web site aims to alleviate physician workforce shortage.

PMID- 19180870
TI  - A comparison of Wisconsin neonatal intensive care units with national data on
      outcomes and practices.
AB  - CONTEXT: Improvements in neonatal care over the past 3 decades have increased
      survival of infants at lower birthweights and gestational ages. However, outcomes
      and practices vary considerably between hospitals. OBJECTIVE: To describe
      maternal and infant characteristics, neonatal intensive care units (NICU)
      practices, morbidity, and mortality in Wisconsin NICUs, and to compare outcomes
      in Wisconsin to the National Institute of Child Health and Human Development
      network of large academic medical center NICUs. METHODS: The Newborn Lung Project
      Statewide Cohort is a prospective observational study of all very low birthweight
      (< or =1500 grams) infants admitted during 2003 and 2004 to the 16 level III
      NICUs in Wisconsin. Anonymous data were collected for all admitted infants
      (N=1463). Major neonatal morbidities, including bronchopulmonary dysplasia (BPD),
      intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and
      retinopathy of prematurity (ROP) were evaluated. RESULTS: The overall incidence
      of BPD was 24% (8%-56% between NICUs); IVH incidence was 23% (9%-41%); the
      incidence of NEC was 7% (0%-21%); and the incidence of grade III or higher ROP
      was 10% (0%-35%). CONCLUSION: The incidence rates of major neonatal morbidities
      in Wisconsin were similar to those of a national network of academic NICUs.

PMID- 19180871
TI  - Women's knowledge of commonly used contraceptive methods.
AB  - INTRODUCTION: Despite the availability of reliable contraceptive methods in this
      country, half of all pregnancies are unintended. There is a scarcity of research
      in a primary care population that measures women's knowledge about commonly used
      contraceptive methods. METHODS: All women between 18 and 40 in the waiting room
      at 2 different family practice clinics were approached over a 2-week period.
      Women were asked to complete a short written questionnaire that included
      demographics, reproductive information, and 9 true/false questions about common
      contraceptive methods. RESULTS: Two hundred fifty-two surveys were completed.
      Half of all women believed that condoms are 99% effective and only 57% knew that
      condoms were not as effective as oral contraceptive pills. Close to half of all
      the women received their contraceptive information from the clinic. Only 42% of
      the women knew that oral contraceptive pills can reduce the incidence of some
      types of cancer. There was not correlation between number of questions answered
      correctly and number of children, type of contraceptive used, age, or
      race/ethnicity. Twenty-six percent of the respondents were not using any
      contraception. DISCUSSION: Overall, the women surveyed demonstrated fairly good
      knowledge of contraception methods. More women surveyed were aware that oral
      contraceptive pills can reduce the rate of uterine and ovarian cancer than in
      previous similar studies. Also, women in this survey were more likely to use
      intrauterine devices than the general population. CONCLUSION: Health care
      professionals should develop more effective education about contraceptive
      methods.

PMID- 19180872
TI  - Patent foramen ovale with right to left shunt as a cause of hypoxia.
AB  - Patent foramen ovale with right to left shunt as a cause of hypoxia without
      Eisenmengers physiology or with only moderately pulmonary artery pressures is an
      uncommon presentation. Initial diagnosis via transesophageal echocardiography
      requires detection of a shunt with either color Doppler or agitated saline
      contrast with or without Valsalva maneuver. This rare but diagnosable case
      presented was simply corrected with placement of a CardioSEAL device. Causes of
      right to left shunt without elevated pulmonary artery pressures are discussed.

PMID- 19180873
TI  - Calciphylaxis responsive to lanthanum carbonate (FOSRENOL) therapy.
AB  - Calciphylaxis is a rare and debilitating vasculopathy predominantly seen in
      patients with renal failure. The proposed mechanism of injury is active vascular
      calcification with associated elevated parathyroid hormone, hypercalcemia, or
      hyperphosphatemia. With improved pharmacologic agents including non-calcium
      containing phosphate binders, vitamin D analogues, calcimimetics, and
      bisphosphonates, targeted therapy on the mineralization process has been tried
      with varied success. We report a case of biopsy-proven calciphylaxis in a patient
      with acute kidney injury requiring dialysis that had persistently elevated
      calcium-phosphorus product refractory to treatment. The patient, however,
      responded rapidly to the initiation of lanthanum carbonate therapy and modified
      dialysis. This is the first known case reported in the literature utilizing this
      new non-calcium-based phosphate binder in the setting of calciphylaxis.

PMID- 19180874
TI  - Thoughts from the White Coat Ceremony.

PMID- 19180875
TI  - Federal Appeals Court reverses lower Court ruling; reaffirms immunity for
      hospitals and physicians in peer review cases.
AB  - Peer review committees in Wisconsin should keep in mind both the Wisconsin peer
      review immunity statute and HCQIA when structuring their peer review processes.
      Documenting that actions were taken in good faith is critical. While this is not
      a consideration under HCQIA, it is under Wisconsin law. Temporary restrictions on
      a physician's privileges can be appropriate when patient safety requires it; in
      these circumstances, hospitals should make sure to keep the issue raised by
      HCQIA's emergency exception. By and large, courts have sided with hospitals in
      peer review disputes. The physician challenging the peer review action bears the
      burden of showing by a preponderance of the evidence that no reasonable belief
      supported the action. While the initial rulings in the Poliner case raised
      concerns, these rulings were not typical and were ultimately reversed. The recent
      ruling by the Appeals Court affirms that HCQIA stands on solid ground, provides
      reassurance to hospitals and physicians engaged in peer review, and advances the
      goals of Congress by allowing peer review committees to take actions that are in
      the best interest of patients. At the same time, physicians subject to review
      retain the right to seek remedies other than money damages and to hold a hospital
      and its medical staff to a reasonable standard conduct that they can reasonably
      implement.

PMID- 19180876
TI  - 2008-2009 recommendations for use of influenza vaccine.

PMID- 19180877
TI  - ProAssurance/PIC WISCONSIN offers preview of rate reductions and coverage
      enhancements.

PMID- 19180878
TI  - Effect of interleukin-1 beta on growth hormone gene expression and its possible
      molecular mechanism in rat MtT/S somatotroph cells.
AB  - OBJECTIVE: To elucidate the effect of interleukin-1 beta (IL-1 beta) on human
      growth hormone (hGH) gene expression in a rat somatotropic pituitary cell line
      MtT/S. METHODS: Stably transfected MtT/S cells were firstly established by
      transfecting 484-Luc1 plasmid which contained hGH gene promoter -484 to +30 bp
      and luciferase reporter gene. The effect of IL-1 beta on hGH gene expression was
      determined by assaying the luciferase activities. RT-PCR method was also used to
      determine whether IL-1 recepor mRNA was expressed in MtT/S cells. RESULTS: The
      10(3) U/mL IL-1 beta stimulated secretion and synthesis of GH, and promoted the
      5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the
      action of 1.38 times above the control. Among inhibitors of signaling
      transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK)
      inhibitor PD98059 (40 micromol/L) and p38 mitogen-activated protein kinase (MAPK)
      inhibitor SB203580 (5 micromol/L) completely blocked the stimulatory effect of IL
      1 beta, and phosphatidylinositol-3-kinase (PI3-K) inhibitor LY294002 partly
      abolished the effect of IL-1 beta. Western blot analysis further confirmed the
      activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over
      expression of Pit-1 nor inhibition of Pit-1 expression affected induction of hGH
      promoter activity by IL-1 beta. A series of deletion constructs of hGH promoter
      were created to identify the DNA sequence that mediated the effect of IL-1 beta,
      and results showed that the stimulatory effect of IL-1 beta was abolished
      following deletion of the -196 to -132 bp fragment. CONCLUSIONS: IL-1 beta
      promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The
      stimulatory effect of IL-1 beta on hGH gene promoter appears to require the
      activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that
      spans the -196 to -132 bp of the gene, but it may be unlinked with Pit-1 protein.

PMID- 19180879
TI  - MiRE: a graphical R package for microRNA-related analysis.
AB  - OBJECTIVE: To provide a set of useful analysis tools for the researchers to
      explore the microRNA data. METHODS: The R language was used for generating the
      Graphical Users Interface and implementing most functions. Some Practical
      Extraction and Report Language (Perl) scripts were used for parsing source files.
      RESULTS: We developed a graphical R package named miRE, which was designated for
      the analysis of microRNA functions, genomic organization, etc. This package
      provided effective and convenient tools for molecular biologists to deal with
      routine analyses in microRNA-related research. With its help, the users would be
      able to build a desktop-centered microRNA research environment quite easily and
      effectively. miRE is freely available at http://www. biosino.org/
      kanghu/WorkPresentation/miRE/miRE.html. A detailed user manual and tutorials with
      example code and image are also available. CONCLUSION: miRE is a tool providing
      an open-source, user-friendly, integrated interface for microRNA-related
      analysis. With its help, researchers can perform microRNA-related analysis more
      efficiently.

PMID- 19180880
TI  - Effects of rapamycin on intracellular cholesterol homeostasis of glomerular
      mesangial cell in the presence of interleukin-1 beta.
AB  - OBJECTIVE: To investigate the effects of rapamycin on cholesterol homeostasis of
      glomerular mesangial cells and the underlying mechanisms. METHODS: Intracellular
      cholesterol accumulation was measured by Oil Red O staining and high performance
      liquid chromatography. The effects of rapamycin on interleukin-1 beta (IL-1 beta)
      induced mRNA and protein changes of low-density lipoprotein receptor (LDLR) and
      ATP-binding cassette transporter A1 (ABCA1) were assayed by quantitative real
      time PCR and Western blot. Transient expressions of 3 types of mammalian target
      of rapamycin (mTOR), including mTOR-WT (wild type), mTOR-RR (rapamycin resistant,
      with kinase activity), and mTOR-RR-KD (rapamycin resistant, without kinase
      activity), were obtained by plasmid transfection. RESULTS: Rapamycin had no
      significant influence on intracellular cholesterol concentration under normal
      condition, but it significantly decreased the intracellular cholesterol
      concentration in the presence of IL-1 beta. Rapamycin dose-dependently suppressed
      the increased expression of LDLR induced by IL-1 beta and up-regulated the
      suppressed expression of ABCA1 caused by IL-1 beta. Transient expression of 3
      types of mTOR all reduced ABCA1 mRNA expression significantly, which all could be
      overroded by rapamycin. CONCLUSIONS: Rapamycin may contribute to the maintaining
      of glomerular mesangial cell intracellular cholesterol homeostasis under
      inflammatory state by both reducing cholesterol uptake and increasing cholesterol
      efflux. And the effect may be not completely mediated by mTOR.

PMID- 19180881
TI  - Survey of airborne pollen in Hubei province of China.
AB  - OBJECTIVE: To study the genera and seasonal distribution of airborne pollen in
      Hubei province of China, and its relationship with pollinosis. METHODS: From
      November 2003 to October 2004, an airborne pollen investigation was performed in
      16 chosen areas in 12 cities of Hubei province using gravity sedimentation
      technique. Meanwhile, univalent skin prick tests of pollens were performed and
      the invasion season was studied on 2,300 patients with pollinosis. Among them,
      352 cases underwent the airway responsiveness measurements, and the correlation
      between airway responsiveness and results of pollen count was analyzed. RESULTS:
      A total of 61 pollen genera were observed and 257,520 pollens were collected. The
      peak of airborne pollen distribution occurred in two seasons each year: spring
      (March and April) and autumn (from August to October). The attack of pollinosis
      corresponded to the peak of pollen distribution. There was a significantly
      negative relationship between the provocation dose causing a 20% decrease of
      forced expiratory volume in one second (FEV1) from baseline and airborne pollen
      concentration (r= -0.6829, P < 0.05). CONCLUSION: This study provides useful
      information for airborne pollen epidemiology of Hubei province, and it provides
      important insights to clinical prevention, diagnosis, and treatment of pollen
      related allergic diseases.

PMID- 19180882
TI  - Management of ureteral endometriosis: a report of ten cases.
AB  - OBJECTIVE: To investigate the clinical features and management of ureteral
      endometriosis. METHODS: Patients surgically and histologically diagnosed as
      ureteral endometriosis from January 2001 to January 2007 in Peking Union Medical
      College Hospital were retrospectively reviewed. RESULTS: Ten patients were
      diagnosed as ureteral endometriosis among 7561 cases with surgically and
      histologically proved diagnosis of endometriosis, with an incidence of 0.132%.
      Nine out of 10 patients were extrinsic ureteral endometriosis and concomitant
      with severe pelvic endometriosis, and the other was intrinsic ureteral
      endometriosis. Hormone therapy failed in 2 patients with urinary tract
      obstruction. Ureterolysis was performed in 6 patients and ureterectomy was
      performed in 4 patients. One case of ureteral recurrence was observed in a
      postmenopausal woman without hormonal replacement therapy who received
      laparoscopic ureterolysis and hysterectomy with bilateral adnexectomy. No relapse
      was observed in the other 9 patients. CONCLUSIONS: Ureteral endometriosis is a
      rare entity. The upper urinary tract should be evaluated in patients with severe
      endometriosis, even in postmenopausal women. The treatment of ureteral
      endometriosis usually requires surgery, while ureterolysis should not be
      performed in patients with extensive disease. As a form of adjuvant therapy of
      surgery, hormonal therapy is an appropriate option.

PMID- 19180883
TI  - Oxidized high-density lipoprotein promotes maturation and migration of bone
      marrow derived dendritic cells from C57BL/6J mice.
AB  - OBJECTIVE: To explore the influence of oxidized high-density lipoprotein (oxHDL)
      on the maturation and migration of bone marrow-derived dendritic cells (BMDCs)
      from C57BL/6J mice. METHODS: The C57BL/6J mice bone marrow cell suspension was
      prepared and purified. Recombinant granulocyte-macrophage colony-stimulating
      factor (rmGM-CSF) and recombinant interleukin-4 (rmIL-4) were used to promote
      monocytes to differentiate and suppress lymphocytes. Then 50 microg/mL oxHDL was
      added to stimulate BMDCs, using 50 microg/mL high-density lipoprotein (HDL) as
      homologous protein control, PBS as negative control, and 1 microg/mL
      lipopolysaccharide (LPS) as positive control. The CD86 and MHCII expression rates
      were detected with fluorescence-activated cell sorting (FACS). Liquid
      scintillation counting (LSC) was used in mixed lymphocyte reactions (MLRs) to
      reflect the ability of BMDCs in stimulating the proliferation of homologous T
      cells. Levels of cytokines IL-12 and IL-10 were detected by ELISA. The cell
      migration was evaluated with the transwell system. RESULTS: Compared with PBS
      group, the expressions of CD86 and MHCII, counts per minute of MLRs, secretion of
      IL-12 and IL-10, and number of migrated cells in oxHDL group and LPS group
      significantly increased (all P<0.05), while the increment was less in oxHDL group
      than LPS group. The number of migrated cells in oxHDL group was about twice of
      that in HDL group. CONCLUSION: OxHDL may promote the maturation and migration of
      BMDCs in vitro.

PMID- 19180884
TI  - Clinical and genetic analysis of three families with familiar amyloid
      polyneuropathy.
AB  - OBJECTIVE: To study the clinical and genetic features of familiar amyloid
      polyneuropathy (FAP). METHODS: Three families of suspected FAP in China mainland
      and Macau were investigated on aspects of clinical manifestations, histological
      features, and gene analysis. RESULTS: All the 3 families had the clinical
      features of sensory and motor polyneuropathies, and notable vegetative nerve
      involvements. Affected cases of one family had ultrasound proved cardiomyopathy.
      Histological studies showed amyloid deposition in all the biopsy tissues of the
      affected cases of the 3 families, and anti-transthyretin antisera staining was
      positive in 3 cases of one family. Gene analysis confirmed that mutation types
      were amyloidogenic transthyretin (ATTR) Val30Met, Phe33Val, and Gly67Glu in the 3
      families respectively. The ATTR Gly67Glu family had a shorter survival time due
      to the heart involvement compared with the other 2 families. CONCLUSION: FAP is
      an autosomal dominant inherited disease, with its clinical manifestations related
      to the type of genetic mutation.

PMID- 19180885
TI  - Implantation of autologous bone marrow mononuclear cells into ischemic myocardium
      enhances coronary capillaries and systolic function in miniswine.
AB  - OBJECTIVE: To investigate the therapeutic effectiveness of intracoronary
      implantation of autologous bone marrow mononuclear cells (BM-MNC) in miniswine
      model of reperfused myocardial infarction. METHODS: Sixteen miniswine myocardial
      ischemic reperfusion injury models made by ligation of the distal one third
      segment of left anterior descending artery for 90 minutes were randomized into 2
      groups. In BM-MNC group (n = 9), (3.54 +/- 0.90) X 10(8) BM-MNC were
      intracoronary injected, and in the control group (n = 7), phosphate buffered
      saline was injected by the same way. Echocardiographic and hemodynamic results,
      vessel density, and myocardial infarction size were evaluated and compared before
      and 4 weeks after cell transplantation. RESULTS: In BM-MNC group, there were no
      differences between before and 4 weeks after transplantation in aspects of left
      ventricular ejection fraction (LVEF), interventricular septal thickness, left
      ventricular lateral and anterior septal wall thickness, cardiac output, or
      +dp/dtmax. In control group, LVEF, interventricular septal thickness, left
      ventricular lateral and anterior septal wall thickness, cardiac output, and
      +dp/dtmax decreased significantly 4 weeks after transplantation (P < 0.05). Left
      ventricular end-diastolic pressure and -dp/dtmax, did not change significantly
      before and after cell transplantation in both groups. Capillary density in BM-MNC
      group was greater than that in control group [(13.39 +/- 6.96)/high power field
      vs. (3.50 +/- 1.90)/high power field, P < 0.05]. Infarction area assessed by
      tetrazolium red staining and the infarction percentage decreased in BM-MNC group
      compared with those in control group (P < 0.05). CONCLUSIONS: Transplantation of
      BM-MNC into myocardium with ischemic reperfusion injury increases capillary
      density and decreases infarction area. It has significantly beneficial effect on
      cardiac systolic function rather than on diastolic function.

PMID- 19180886
TI  - Myocardial lesions after long-term administration of methamphetamine in rats.
AB  - OBJECTIVE: To demonstrate the myocardial lesion associated with long-term
      administration of methamphetamine in rats. METHODS: The experimental models of
      intoxication of methamphetamine were established in Sprague-Dawley rats.
      Methamphetamine hydrochloride (3 mg x kg(-1) x d(-1)) was subcutaneously injected
      to rats in methamphetamine-treated group (n = 16), and normal saline at the same
      dose was injected to rats in control group (n = 16). After 1 week and 8 weeks of
      injection, 8 rats in each group were sacrificed and their hearts were examined
      with light microscopy and electron microscopy, respectively. RESULTS: After 1
      week of methamphetamine exposure, foci of contraction band and cellular
      degeneration were present in subendocardial myocardium. Cellular degeneration,
      myocytolysis, and contraction band necrosis became prominent and extensive in
      methamphetamine-treated rats after 8 weeks. Hypertrophy, intracellular
      vacuolization, and fibrosis were also observed. The ultrastructural feature
      showed marked swelling and degeneration of mitochondria, enlargement of
      sarcoplasmic reticulum, and dissolution of myofilaments. No obvious cardiac
      myocyte lesions were observed in rats of control group. CONCLUSION:
      Methamphetamine abuse daily for a long time may result in an increased risk of
      cardiovascular lesions similar to cardiomyopathy.

PMID- 19180888
TI  - Prevalence of impaired glucose regulation in the population of Tianjin.
AB  - OBJECTIVE: To investigate the prevalence of impaired glucose regulation (IGR) in
      the population of Tianjin. METHODS: A cross-sectional study was conducted in
      Tianjin from June to September in 2005. The multi-phasic stratified cluster
      sampling method was adopted. Totally, 21,454 people were selected as survey
      sample. Information on risk factors was collected through face-to-face
      questionnaire interview. Fasting capillary whole blood glucose level and other
      clinical indexes were tested. RESULTS: The prevalence of impaired fasting glucose
      (IFG) in the population was 5.61% (5.32% in male, 5.89% in female). The
      prevalence of impaired glucose tolerance (IGT) was 2.91% (2.59% in male, 3.20% in
      female) in whole population, and the prevalence of female was significantly
      higher than that of male (P = 0.04). The prevalences of IFG and IGT increased
      with the increasing of age. And the prevalences were also influenced by the
      profession, educational level, and income level. CONCLUSION: The prevalences of
      IGT and IFG in Tianjin are similar to those in the other big cities of China.

PMID- 19180887
TI  - Two-year observation of a randomized trial on tacrolimus-based therapy with
      withdrawal of steroids or mycophenolate mofetil after renal transplantation.
AB  - OBJECTIVE: To evaluate the safety and feasibility of steroid or mycophenolate
      mofetil (MMF) withdrawal from tacrolimus-based immunosuppressant regimen in renal
      allograft recipients. METHODS: A cohort of 45 patients following cadaveric renal
      allograft transplantation were randomly divided into 3 groups based on the
      regimen of combination of tacrolimus, steroid, and MMF: triple therapy group,
      steroid withdrawal group, and MMF withdrawal group. During 2 years, survival of
      patients and allografts, clinical acute rejection, adverse events, hepatic and
      renal allograft function, and blood lipids were monitored to evaluate the safety
      and feasibility of steroid or MMF withdrawal after renal transplantation.
      RESULTS: During two-year observation, steroid or MMF was successfully withdrawn
      from immunosuppressant regimen based on tacrolimus without any clinical acute
      rejection. Patient and graft survival rates were 100% and all the renal
      allografts kept excellent function. Some adverse events occurred and there were
      no significant differences among groups. CONCLUSION: Withdrawal of steroid or MMF
      in low-immunological-risk renal allografts treated with tacrolimus-based
      immunosuppressant regimen can be achieved with no increased risk of acute
      rejection.

PMID- 19180889
TI  - Disqualifying medical conditions of flying personnel in Chinese Army and Air
      Force.

PMID- 19180890
TI  - Anatomic considerations for soft tissue augmentation of the face.

PMID- 19180891
TI  - Histologic and clinical response to varying density settings with a fractionally
      scanned carbon dioxide laser.
AB  - OBJECTIVE: An evaluation of the histological and clinical response to varying
      density settings (-10%, 0, and 10% overlap) with a fractionally scanned CO2
      laser. STUDY DESIGN: Clinical and histological study evaluating abdominoplasty
      excised tissue for depth of penetration and width of tissue ablated with varying
      density and energy settings utilizing a scanned microsecond pulsed CO2 laser.
      These parameters were correlated clinically with patients treated with similar
      density settings. PARTICIPANTS: Fifteen patients were enrolled with 5 patients in
      each group: group 1 (density 1 settings), group 2 (density 2 settings) and group
      3 (density 3 settings). MAIN OUTCOME: Histological differences of width and depth
      of tissue ablated with varying density settings and correlation with photodamage
      improvement clinically. METHODS: Six samples of excised abdominoplasty tissue
      were treated with increased energy and density settings and were evaluated
      histologically. Clinically, 15 patients with photodamage to the face were
      randomized to receive a fractional CO2 laser treatment with density levels
      ranging from 1 to 3. RESULTS: Microarrays of tissue injury were visualized with
      multiple areas of superficial to full-thickness epidermal thermal damage. As
      energy increased (90 W to 100 W), the width of basophilic coagulation of the
      subepidermal collagen increased. Increased density paralleled increased depth of
      penetration of subepidermal coagulation. Patient assessment of discomfort,
      erythema, edema, and satisfaction with the procedure was proportional to
      increasing densities. CONCLUSION: A fractional CO2 laser produces
      photorejuvenation, erythema, edema and discomfort in proportion with the depth
      and extent of epidermal and subepidermal thermal damage.

PMID- 19180892
TI  - Linear closure for nasal defects after Mohs micrographic surgery.
AB  - BACKGROUND: Skin cancers on the nose are very common. Excision of these tumors
      results in surgical defects that can pose a challenge to repair. OBJECTIVE: To
      present the authors' experience of using linear closures (LC) to repair surgical
      defects on the nose in patients who underwent Mohs micrographic surgery (MMS).
      METHODS: A retrospective analysis was conducted of 4765 patients with skin
      malignancies on the nose that were treated with MMS between July 1997 and January
      2006. The following variables were examined: type of repair, age, and sex of the
      patients, postoperative size of the defect, type of malignancy, location of the
      defect, and final length of the closure. Short-term and long-term complications
      were evaluated and discussed. In a second study arm, a limited prospective
      cosmetic outcome assessment of patients with nasal defects repaired by LC
      compared to flaps and grafts was also conducted. RESULTS: There were 2053
      patients (1020 men and 1033 women) who underwent LC of nasal defects after MMS.
      The average postoperative defect size was 1.7 x 0.9 cm, with an average closure
      length of 2.7 cm (range: 0.6 cm to 8.5 cm). The 2 major malignancies treated were
      basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Short-term
      complications were minimal. Nasal asymmetry and/or raising of the nasal alae were
      occasionally seen, which improved over time. The cosmetic outcomes of the LC
      group were rated higher than the flap/graft group for lesions on the nose,
      although this was not statistically significant. CONCLUSIONS: A vertical or
      slightly vertical linear closure for nasal defects after Mohs micrographic
      surgery is a robust and reliable method to deliver excellent cosmetic and
      functional results. Linear closure should be considered for small and mid-sized
      cutaneous nasal defects whenever possible.

PMID- 19180893
TI  - Topical sulindac combined with hydrogen peroxide in the treatment of actinic
      keratoses.
AB  - BACKGROUND: Actinic keratoses (AKs) are a precancerous condition of the skin that
      have the potential to become squamous cell cancer (SCC). Sulindac is a Food and
      Drug Administration (FDA)-approved nonsteroidal anti-inflammatory drug (NSAID)
      that has been shown to have clinically significant anticancer effects. Malignant
      cells may have a different response to oxidative stress than normal cells.
      OBJECTIVE: To establish a role of increased reactive oxygen species (ROS) in the
      mechanism of cancer killing by sulindac in the presence of an oxidizing agent. To
      assess the tolerability and efficacy of the combination of gels containing
      sulindac and hydrogen peroxide in the treatment of patients with AKs. METHODS:
      Cell culture studies were performed using a skin SCC cell line and normal human
      epidermal keratinocytes. After treatment with sulindac and an oxidizing agent,
      cell viability, and intracellular ROS levels were measured. An open-label
      clinical trial was performed using sulindac and hydrogen peroxide gels daily for
      3 weeks on AKs involving the upper extremities. RESULTS: In SCC cells, a
      combination of sulindac and an oxidizing agent lead to 400 to 500% increases in
      intracellular ROS, which resulted in significant cell death. In sharp contrast,
      normal keratinocytes did not show increases in ROS levels and were not killed. A
      clinical trial using the combination of sulindac and hydrogen peroxide therapy in
      5 patients with AKs revealed that 60% of the treated AKs responded and 50% showed
      no residual AK on histopathology specimens after skin biopsy. LIMITATIONS: The
      small number of patients and the lack of a placebo group. CONCLUSION: Increased
      levels of ROS appear to be important in the selective killing of cancer cells in
      the presence of sulindac and oxidizing agents. Further studies are necessary to
      define the role of the combination of sulindac and oxidizing agent therapy in
      patients with AKs and skin cancer.

PMID- 19180894
TI  - Treatment of actinic keratoses with sequential use of photodynamic therapy; and
      imiquimod 5% cream.
AB  - BACKGROUND: Field-directed therapies for actinic keratosis include photodynamic
      therapy and imiquimod. OBJECTIVES: The author designed a randomized, vehicle
      controlled, split-face study to explore the safety and efficacy of photodynamic
      therapy followed by imiquimod. METHODS: The entire face of adults with > or =10
      facial actinic keratoses were treated with photodynamic therapy with
      aminolevulinic acid 20% at baseline and at month 1. At month 2, imiquimod 5%
      cream was applied to one-half of the face and vehicle to the other half, 2-times
      per-week for 16 weeks. Lesion counts were performed at baseline and months 1, 2,
      3, 4, 6, and 12; and local skin reactions assessments at months 2, 3, 4, and 6.
      RESULTS: Of 25 participants enrolled, 24 completed the study. Baseline median
      lesions were 23.5 and 21.5 for the imiquimod- and vehicle-treated sides,
      respectively. At month 12, median lesion reductions was 89.9% versus 74.5%
      (P=.0023), respectively. No subject discontinued for an adverse event. Severe
      local skin reactions occurring in the most participants were erythema (17%) and
      flaking/scaling/dryness (13%). CONCLUSIONS: Photodynamic therapy followed by
      imiquimod was well tolerated and improved reduction of actinic keratoses.

PMID- 19180895
TI  - Methylene blue mediated photodynamic therapy for resistant plaque psoriasis.
AB  - Topical treatment of resistant psoriatic plaque stage lesions may be difficult
      and the systemic therapies seem inappropriate. Therefore, a topical 0.1%
      methylene blue (MB) hydrogel was prepared and evaluated for percent drug content,
      drug uniformity, pH, rheological and organoleptic characters such as feel
      tackiness, grittiness sensation, and transparency in addition to release kinetics
      study in vitro. The efficiency of the photodynamic therapy (PDT) of MB photo
      activated using 565 mW Light emitting diode (LED) 670 nm was evaluated in
      patients with resistant plaque psoriasis. The gel was evaluated in single blinded
      study. The patients were subjected to repeated sessions of irradiation, skin
      biopsies from each patient in the beginning and at the end of the sessions were
      taken for histopathological studies. Results showed the hydrogel was transparent
      nongritty and the drug uniformly dispersed with pH=7.2 and viscosity value=25.04
      Pa. The drug content was found to be 99.4 +/- 0.15 %. Drug release was following
      zero order kinetics with rate constant K=0.348 +/- 0.01 and T(1/2) = 0.95 +/- 0.5
      hours. Sixteen patients experienced complete clearance of their treated lesions.
      Skin appeared normal in color, texture, and pliability with no complications
      indicating the lack of skin sensitivity. Histopathological examinations showed
      nearly normal epidermis at the end of all sessions. The authors concluded that
      the prepared hydrogel was safe, stable, and very effective. The results are
      encouraging to accept MB as a photosensitizer for PDT and as a safe and effective
      method for treatment of selected cases of resistant localized psoriasis

PMID- 19180896
TI  - Comparing clobetasol propionate 0.05% spray to calcipotriene 0.005% betamethasone
      dipropionate 0.064% ointment for the treatment of moderate to severe plaque
      psoriasis.
AB  - Topical corticosteroids are widely used in the treatment of psoriasis. This study
      was conducted to compare the efficacy and safety of clobetasol propionate (CP)
      0.005% spray to calcipotriene 0.005%-betamethasome diproprionate 0.064% (C-BD)
      ointment in patients with moderate to severe plaque psoriasis. Assessments were
      made at baseline, week 2, week 4 (end of treatment) and week 8 (4 weeks
      posttreatment). An assessment for Overall Disease Severity (ODS) found that 75%
      of CP spray-treated patients achieved a rating of clear or almost clear after 4
      weeks of treatment compared to 45% of C-BD ointment-treated patients (P=.003).
      Adverse events were reported by less than one-third of patients from each
      treatment group (31% for CP spray and 33% for C-BD ointment).

PMID- 19180897
TI  - Photodistributed erythema multiforme: paclitaxel-related, photosensitive
      conditions in patients with cancer.
AB  - Paclitaxel (Taxol) is an intravenously administered antineoplastic agent derived
      from the yew tree, Taxus brevifolia, whose mechanism of action involves
      inhibition of mitosis. Some of the mucocutaneous reactions to the drug that have
      been observed include alopecia, mucositis, hypersensitivity reactions (with
      erythema and urticaria), nail changes, changes occurring at intravenous sites,
      and radiation recall dermatitis. Less commonly, acral erythema, erythema
      multiforme, pustular dermatitis, and scleroderma-like changes have been
      described. A female patient who was receiving adjuvant weekly paclitaxel for the
      treatment of intraductal breast carcinoma developed photodistributed erythema
      multiforme and onycholysis after sun exposure to the affected areas. Including
      this woman, paclitaxel-associated photosensitve conditions have only been
      reported in 9 female oncology patients: onycholysis (5), erythema multiforme and
      onycholysis (2), photo-recall phenomenon (1), and subacute cutaneous lupus
      erythematosus (1). The patients were either receiving treatment for breast
      carcinoma (8) or lung cancer (1). The skin lesions developed on sun-exposed
      areas, usually after the patient had received several weekly doses of paclitaxel,
      and resolved following discontinuation of the drug. Several of the patients were
      subsequently able to receive additional cycles of paclitaxel without recurrence
      of their drug-associated photosensitive conditions by concurrently using
      photoprotection to prevent additional sun exposure to the previously affected
      sites during treatment.

PMID- 19180898
TI  - Ablative fractionated erbium:YAG laser for the treatment of ice pick alar scars
      due to neodymium:YAG laser burns.
AB  - The authors present a case of ice pick scars forming in the nasal alar grooves of
      a patient who was treated with a 1064-nm neodymium:yttrium-aluminum-garnet
      (Nd:YAG) laser for facial telangiectasias. Treatment options for these types of
      scars are reviewed and specifically we report the success of an ablative
      fractionated 2940-nm erbium:yttrium-aluminum-garnet (Er:YAG) laser.

PMID- 19180899
TI  - Permanent hyperpigmentation following laser hair removal using the dynamic
      cooling device.

PMID- 19180900
TI  - Treatment for multiple periorbital eccrine hidrocystomas: botulinum toxin A.
AB  - Hidrocystomas are relatively common cystic lesions that can display either
      apocrine or eccrine differentiation. While numerous treatment modalities exist
      for solitary hidrocystomas including simple excision, electrodesiccation, and CO2
      laser, treatment of multiple hidrocystomas can be challenging. A 38-year-old,
      black female with a 23-year history of multiple periorbital cystic nodules
      presented to the clinic with the complaint of lesions that were increasing in
      size and number. Prior treatment included excision resulting in scarring without
      significant clinical improvement. Initially, incision and drainage was performed
      with flattening of the cysts; however, the cystic nodules refilled to baseline by
      6 weeks. Subsequently, intralesional botulinum toxin type A was offered as an
      alternate therapy in conjunction with incision and drainage. The patient reported
      sustained flattening of the lesions at both 1-month and 4-month follow-up
      appointments. Intralesional botulinum toxin A offers a novel treatment for
      patients with multiple hidrocystomas that have failed other therapies.

PMID- 19180901
TI  - Treatment of inverse psoriasis with efalizumab.
AB  - Various topical and systemic treatments have shown efficacy in plaque and
      palmoplantar psoriasis; however, studies regarding efficacy in inverse psoriasis
      are few. The authors present a case of a patient with severe inverse psoriasis
      who was successfully treated with efalizumab, resulting in complete and sustained
      remission during prolonged maintenance therapy.

PMID- 19180902
TI  - Allergies in children, adults with generalized rashes, testing before metal
      implants, and cosmetic allergies.

PMID- 19180903
TI  - Adults with generalized dermatitis: what are the common contact allergens?

PMID- 19180904
TI  - Observations on the use of fractionated CO2 laser resurfacing.

PMID- 19180905
TI  - [Concerns about vertigo].
AB  - Vertigo is an erroneous perception of movement resulted from the disorder of
      spatial orientation. The diagnosis and treatment of vertigo is complexand it is
      urgent to pay more attention on the research in this disease and standardize the
      management protocol.

PMID- 19180906
TI  - [Vestibular pathology associated with noise-induced inner ear impairment].
AB  - OBJECTIVE: To evaluate the pathological status of the vestibular system
      associated with noise-induced inner ear impairment. METHODS: Totally 68 patients
      with noise-induced hearing loss (NIHL) who presented with vestibular symptoms
      including vertigo, dizziness, and chronic disequilibrium were screened. All
      patients underwent a series of conventional vestibular function tests and
      vestibular autorotation test and the results were retrospectively reviewed and
      evaluated. RESULTS: Sixty-eight (14.5%) patients with NIHL were identified among
      469 patients with vertigo, dizziness, or imbalance. A pure tone hearing threshold
      of patients with vertigo and NIHL at 4000 Hz were between 30 dB HL and 80 dB HL
      with an average threshold of (46.7 +/- 17.6) dB HL in left ear and (37.3 +/-
      16.7) dB HL in right ear. Patients with symmetrical hearing loss at 4000 Hz
      accounted for 41.7% and those with asymmetrical loss accounted for 58.3%.
      Vestibular pathologies included benign positional paroxysmal vertigo (45.7%),
      unilateral decreased caloric responses (20.0%), bilateral decreased caloric
      responses (26.7%), abnormal vestibulo-spinal reflex function (28.6%), vestibular
      function response hyperactivity (3.0%), and abnormal vestibulo-ocular reflex
      presentation at high frequencies (97.0%). CONCLUSIONS: Loud acoustic stimulation
      not only damages the cochlea but also causes clear functional impairment to the
      vestibular end organs. Although the vestibular pathology is not correlated with
      the severity of the hearing loss, it correlates with the subjective symptoms of
      the vestibular system.

PMID- 19180907
TI  - [Visual evoked potentials in adults with migrainous vertigo].
AB  - OBJECTIVE: To investigate the visual evoked potentials in adults with migrainous
      vertigo (MV). METHODS: Totally 113 patients with MV were enrolled from vertigo
      clinic. Patients received necessary laboratory examinations as well as pattern
      visual evoked potential (PVEP) testing. RESULTS: Definite MV accounted for 46.9%
      (53/113) and probable MV accounted for 53.1% (60/113). Among 74 patients who
      received PVEP, the results were normal in 35 patients (47.3%) and abnormal in 39
      patients (52.7%). The abnormal manifestations included lowered N75-P100
      amplitude, elongated latency of P100, and lowered N75-P100 amplitude combined
      with delayed latency of P100. Seven patients with MV had unilateral lowered N75
      P100 amplitude and 4 had bilateral abnormal amplitude. Nine patients had
      unilateral delayed latency of P100 and 11 had bilateral abnormal latency. Four
      patients had unilateral and 4 had bilateral abnormal N75-P100 amplitude and
      latency of P100. CONCLUSIONS: MV patients usually have abnormal PVEP. PVEP may
      become a useful electrophysiological test in the diagnosis of MV.

PMID- 19180908
TI  - [Investigation and analysis of the baseline data of 3432 patients with vertigo].
AB  - OBJECTIVE: To analyze the baseline data of outpatient clinical subjects with
      vertigo and study on the clinical characteristics of vertigo. METHOD: The
      questionnaires and clinical tests data of 3432 patients complained vertigo were
      retrospectively analyzed. RESULTS: All the patients received interview and
      vestibular function test. These patients aged 4-89 years with an average age of
      (40 +/- 18.6) years. Among them 1513 (44.09%) were male and 1919 (55.91%) were
      female, with a male:female ratio of 1:1.27. Vertigo patients increased according
      to age and reached its peak in the 41-60 years among all patients. The incidence
      might increase along with the increase of education level in urban populations.
      The onset of vertigo might correlate with the careers but differed among
      different populations. CONCLUSIONS: Vertigo attacks patients in all age spans,
      but vertigo is highly prevalent in the population aged 41-60 years. The onset of
      vertigo is related to many different factors.

PMID- 19180909
TI  - [Endolymphatic visualization in patients with Meniere's disease].
AB  - OBJECTIVE: To attempt to visualize the endolymph in patients with Meniere's
      disease by applying non-invasive intratympanic gadolinium through eustachian tube
      and three-dimensional fluid-attenuated inversion recovery magnetic resonance
      imaging (3D-FLAIR MRI). METHODS: With a 3 Tesla magnetic resonance imaging (MRI)
      unit, 3D-FLAIR imaging was performed 24 hours after intratympanic gadolinium
      through eustachian tube in two patients with medically active and intractable
      Meniere's disease. Pure tone test and tympanometry were performed 24 hours before
      and after the administration of gadolinium. RESULTS: The gadolinium appeared in
      almost all parts of the perilymph inside the inner ear; moreover, the border
      between the perilymph and the endolymph was visible so endolymphatic space was
      clearly shown on 3D-FLAIR. No change in pure tone test and tympanometry was
      noted. CONCLUSIONS: 3D-FLAIR MRI with intratympanic gadolinium through eustachian
      tube can clearly reveal the visualization of endolymph in patients with Meniere's
      disease. Intratympanic gadolinium therapy through eustachian tube is a safe and
      effective.

PMID- 19180910
TI  - [Expressions of c-Fos and NADPH-d in the related brainstem during vestibular
      compensation].
AB  - OBJECTIVE: To study the mechanism of vestibular compensation and to observe the
      changes of c-Fos and NADPH-d expressions in the brainstem of the vestibular
      deafferentation rats in static status or following angular acceleration
      stimulation. METHODS: Totally 60 SD rats were randomly divided into control group
      (labyrinthine intact), complete unilateral vestibular deafferentation (UVD)
      group, simultaneous complete bilateral vestibular deafferentation (BVD) group (n
      = 20 in each group). Subgroups (n = 10 in each subgroup) were set for static
      status or following angular acceleration stimulation in each group. Double
      labeling with histochemistry-immunohistochemistry was performed to observe c
      Fos/NADPH-d neurons. RESULTS: No positive c-Fos/NADPH-d expression was observed
      in the both sides of medial vestibular nucleus (MVN) and prepositus hypoglossi
      (PrH) of normal rats in static status and BVD rats whether following canal
      rotation or not. c-Fos/ NADPH-d expression was observed in the ipsilesional MVN
      and the contralesional PrH of UVD rats. However, c-Fos/NADPH-d were detected in
      both sides of MVN and PrH in UVD rats and normal rats following angular
      acceleration stimulation. CONCLUSION: In the ipsilesional MVN and the
      contralesional PrH, c-Fos plays an important role in vestibular compensation, in
      which nitric oxide acts as a key neurotransmitter.

PMID- 19180911
TI  - [Effect of vasopressin on aquaporin 7 expression in rat inner ear].
AB  - OBJECTIVE: To study the effect of vasopressin on aquaporin 7 (AQP7) expression in
      rat inner ear and reveal the possible role of aquaporins in the formation of
      endolymphatic hydrops induced by vasopressin. METHODS: Wistar rats were
      intraperitoneally injected with 50 microg/kg arginine vasopressin once a day for
      one week. Differentially expressed genes of aquaporins induced by vasopressin
      injection in rat inner ear were filtered by cDNA microarray. The changes of mRNA
      expression level of AQP7 in inner ear of rats treated with vasopressin injection
      were measured by RT-PCR. RESULTS: Differentially expressed gene AQP7 of
      aquaporins induced by vasopressin injection was screened out in rat inner ear.
      The expression level of AQP7 mRNA in inner ear of rats treated with vasopressin
      injection was significantly lower. CONCLUSION: Vasopressin may down-regulate the
      expression of AQP7 mRNA in the endolymphatic sac and induce a decreased
      absorption of endolymph, which decreases the water permeability in the potassium
      ions recycle pathway in the organ of Corti and disturbs the circulation of
      endolymph, resulting in endolymphatic hydrops.

PMID- 19180912
TI  - [Normal values of vestibular autorotation test in young people].
AB  - OBJECTIVE: To explore the normal values of vestibular autorotation test (VAT) in
      young people. METHODS: VAT was performed in 31 young people aged 20-30 years. The
      measured value were analyzed and compared with the reference normal value.
      RESULTS: The measured values of VAT in healthy young people are almost within the
      normal range of the general population. Compared with the reference normal
      values, the horizontal gains at 2.0, 2.3, 2.7, 5.5, and 5.9 Hz, the vertical
      gains at 2.0 and 5.9 Hz, and the vertical phases at 2.0, 2.3, 2.7, 3.1, 3.5, and
      3.9 Hz were significantly different (P < 0. 05). No significant difference was
      shown in the horizontal phases and asymmetry. CONCLUSIONS: The normal values of
      VAT in young people is within the reference normal range of the general
      population. The vestibular function of young people may be more sensitive in
      lower frequency range (2-3Hz).

PMID- 19180913
TI  - [Value of anal sphincter electromyography, orthostatic hypotension and dizziness
      in diagnosing multiple system atrophy].
AB  - OBJECTIVE: To explore the value of anal sphincter electromyography (ASEMG),
      orthostatic hypotension (OH), and dizziness in diagnosing multiple system atrophy
      (MSA). METHOD: The characteristics of ASEMG and OH were compared among patients
      with dizziness (MSA and non-MSA), patients without OH (MSA and non-MSA), and
      patients with probable MSA (OH and non-OH). RESULTS: Totally 476 patients
      underwent ASEMG examinations. Dizziness was the onset symptom in 69 patients.
      Between the MSA group and non-MSA group, the mean duration of dizziness [(14.6 +/
      2.1) vs. (12.8 +/- 2.0) ms, P < 0.01] and satellite potential occurrence rate
      [(22.7 +/- 11.8)% vs. (12.2 +/- 8.9)% , P < 0.01] were significantly different,
      while the OH rate (84.6% vs. 55.2% ) and the difference of the blood pressure
      between standing and supine positions were not significantly different. In 162
      patients with symptom of dizziness, the mean duration of dizziness [(15.3 +/-
      2.7) vs. (12.8 +/- 1.9) ms, P < 0.001], satellite potential occurrence rate
      [(25.4 +/- 12.8)% vs. (13.5 +/- 10.4)%, P < 0.001] , and difference of the
      diastolic blood pressure [(18.5 +/- 17.0) vs. (11.7 +/- 12.7) mmHg, P < 0.05]
      were significantly different between the MSA group and non-MSA group, while the
      normal rate of blood pressure at standing position (60% vs. 41.9%) and the
      difference of systolic blood pressure were not significantly different. In 146
      patients with abnormal blood pressure at standing and supine positions, the mean
      duration of dizziness [(15.0 +/- 2.4) vs. (12.8 +/- 1.7) ms, P < 0.001] and
      satellite potential occurrence rate [(22.0 +/- 12.2)% vs. (10.6 +/- 8.5)%, P <
      0.001] were significantly different between the MSA group (n = 61) and non-MSA
      group (n = 85). In 125 patients with probable MSA, the mean duration of dizziness
      [(15.5 +/- 2.4) vs. (15.9 +/- 2.2) ms, P > 0.05] and satellite potential
      occurrence rate [(24.3 +/- 12.6)% vs. (22.7 +/- 12.4)%, P > 0.05] were not
      significantly different between those with OH and those without OH. The rates of
      dizziness and the percentage of dizziness as the onset symptom were 93.2% and
      52.3% in OH group and 44.4% and 8.3% in non-OH group. CONCLUSIONS: ASEMG is
      better than OH in diagnosing patients with dizziness suspected as MSA. Neurogenic
      lesion can be found by ASEMG in patients without OH, which is helpful in the
      early diagnosis of MSA.

PMID- 19180914
TI  - [Clinical analysis of normal subjects and dizzy patients with postural sway
      test].
AB  - OBJECTIVE: To study the characteristics of the normal subjects with postural sway
      test and discuss the value of postural sway test in the diagnosis of dizzy
      patients. METHODS: Totally 112 normal subjects, 72 patients with peripheral
      vertigo, and 30 patients with central vertigo were examined using a stabilometer
      (EAB-100, Anima Co., Japan). Items include patterns, length of locus, envelope
      area, deflection average center displacement, and romberg rate were recorded and
      compared. RESULTS: The postural sway was classified into the following five
      patterns: centripetal, forward and backward, right and left, diffuse, and
      multicentric. Centripetal pattern was the most prominent figure pattern in the
      normal subjects, while diffuse pattern was the most prominent figure pattern in
      the patients with central vertigo. When the normal subjects closed their eyes,
      age was linearly correlated with the length of locus, envelope area, rectangel
      area, and unit area path length (P < 0.05). Sex was not correlated to all of
      these parameters. The length of locus and envelope area in the patient groups
      were significantly increased when compared with the normal subjects (P < 0.0167).
      Romberg rate was not significantly different between the patients and the normal
      subjects. CONCLUSIONS: The pattern of postural sway is useful for the diagnosis
      of vertigo. Age is an important factor that affects the balance function. Sex
      seems has no influence. Visual input plays an important role in maintaining
      postural balance. Stabilometer is a useful tool for evaluating balance function,
      and postural sway test may be a valuable assistant examination.

PMID- 19180915
TI  - [Pathogenesis of benign paroxysmal positional vertigo].
AB  - OBJECTIVE: To explore the etiological factors of benign paroxysmal positional
      vertigo (BP-PV). METHODS: The clinical data of 145 patients with BPPV were
      retrospectively reviewed. The impacts of gender and age on BPPV were analyzed.
      The relationship between the onset of BPPV and the internal ear ischemia was also
      explored. RESULTS: The abnormality rate of auditory brainstem response (ABR)
      under high stimulus rate was 59.3% (86/145) in all the patients with, including
      22.1% (32/145) in male and 37.2% (54/ 145) in female (P > 0.05). The abnormality
      rate of ABR under high stimulus rate were 37.9% (55/145) and 21.4% (31/145) in
      middle-aged (30-55 years) and old ( > 55 years) patients, respectively (P >
      0.05). CONCLUSION: The onset of BPPV may relate to ischemic internal ear but is
      not relevant with gender and age.

PMID- 19180916
TI  - [Perfusion characteristics of renal mass with 64-slice spiral computed
      tomography].
AB  - OBJECTIVE: To investigate the perfusion characteristics of renal mass parenchyma
      on 64-slice spiral computed tomography (CT). METHODS: Totally 91 patients with
      renal mass were enrolled. Sixty-four slice spiral CT was used for renal perfusion
      scan that began with a contrast bolus injection of 50 ml (370 mgI/ml) at a rate
      of 5 ml/s. Perfusion characteristics, including blood flow (BF), blood volume
      (BV), and permeability (PM) of renal mass parenchyma and renal cortex in affected
      and normal kidneys were calculated from Siemens Body PCT (VB20B) software, and
      the perfusion characteristics among renal mass parenchyma and renal cortex in
      affected and normal kidneys were compared. RESULTS: Renal clear cell carcinoma
      (RC-CC), renal pelvic transitional cell carcinoma (RPTCC), and renal
      angiomyolipoma (RAML) was pathologically confirmed in 40, 21, and 16 patients,
      respectively, while the remaining 14 patients were diagnosed as with renal simple
      cyst (RSC). Technical failure was experienced in 1 (1.1% ) patient. Perfusion
      parameters of tumor parenchyma were measured as follow: RCCC, BF (93.7 +/- 20.2)
      ml x (100 ml)(-1) x min(-1), BV (182.0 +/- 46.6) 1000:1, PM (115.7 +/-30.2) 0.5
      ml x (100 ml)(01) x min(-1); RPTCC, BF (48.0 +/- 21.2) ml x (100 ml)(-1) x min(
      1), BV (82.4 +/- 29.7) 1000:1, PM (65.7 +/- 17.2) 0.5 ml (100 ml)(-1) x min(-1);
      RAML, BF (52.6 +/- 18.5) ml x (100 ml)(-1) x min(-1), BV (110.1 +/- 45.9) 1000:1,
      PM (60.1 +/- 23.0) 0.5 ml x (100 ml)(-1) x min-1; RSC, BF (7.0 +/- 6.5) ml x (100
      ml)(-1) min(-1), BV (16.2 +/- 9.7) 1000:1, PM (12.0 +/- 7.2) 0.5 ml x (100 ml) (
      1) x min(-1). In all pathological groups, perfusion pa- rameters showed
      significant differences (P <0 . 1) between mass parenchyma and renal cortex in
      affected kidney, while there were no significant differences (P > 0. 5) in
      perfusion characteristics between renal cortex in affected and normal kidneys.
      Aslo, the perfusion characteristics were significantly different between
      parenchyma D in any two kinds of renal masses (P <0 . 5) except for RPTCC and
      RAML (P > 0. 5). C ONCLUSIONS: fDif-rent pathological types of renal mass have
      different perfusion characteristics. Perfusion imaging with multislice CT is
      potentially useful in the differential diagnosis of renal mass.

PMID- 19180917
TI  - [Ultrasound elastography of ethanol-induced hepatic lesions].
AB  - OBJECTIVE: To study the value of ultrasound elastography in the evaluation of
      ethanol-induced lesions of liver. METHODS: Alcohol with a dose of 2 ml was
      injected into a fresh porcine liver under ultrasound guidance to create stiff
      necrosis. Then freehand elastography of the lesion from the identical scan plane
      was obtained with Siemens SONOLINE Antares system using VF10-5 probe at about
      every 30 seconds till 6 minutes later. The original high-quality radio-frequency
      data were acquired through an ultrasound research interface provided by the
      ultrasound system. Corresponding elastograms were then produced offline using
      cross-corre-lation technique and compared with gross specimen. RESULTS: A
      hyperechoic area with acoustic shadow below appeared immediately after alcohol
      injection. The hyperechoic area diffused and its boundary was illegible following
      injection. On the contrary, the ethanol-induced lesion in elastography appeared
      as a low strain hard region surrounded by high-strain soft hepatic tissues with
      clear but irregular boundaries. Sequential elastograms with the lesion boundaries
      sketched showed that the lesion area grew in the first 3 minutes after ethanol
      injection and then reached a plateau, which corresponded to the gross specimen.
      CONCLUSION: Ultrasound elastography can be used to detect and evaluate the
      diffusion of ethanol-induced hepatic lesion.

PMID- 19180918
TI  - [Construction and expression of anti-tumor necrosis factor related apoptosis
      inducing ligand receptor death receptor 5 chimeric antibody in eukaryotic cells].
AB  - OBJECTIVE: To construct the human/mouse chimeric antibody of a functional anti
      death receptor 5 (DR5) antibody. Methods The viable region of light chain (VL)
      and viable region of heavy chain (VH) genes of anti-DR5 antibody were amplified
      and cloned into the light- and heavy-chain expression vectors respectively, then
      the recombinant plasmids were co-transfected into dihydrofolate reductase(-)
      Chinese hamster ovary cell (CHO-dhfr(-)) for expression. The positive clone was
      screened by the two selective genes (neo and dhfr). The humanization and
      specificity of chimeric antibody was identified by ELISA and Western blotting,
      and the tumoricidal activity of the expressed chimeric antibody was detected by
      tetrazolium salt phenazine methosulfate assay. RESULTS: The expression vectors
      stably expressed chimeric antibody in CHO-dhfr(-). In the cell supernatant of the
      F4' clone, the human IgG heavy constant region and light constant region were
      identified. Moreover, the secreted chimeric antibody retained the binding
      capacity to the antigen (DR5) and decreased the cell viability of Jurkat and
      HCT116 cells to 73.15% and 77.30% in vitro respectively. CONCLUSION: The
      human/mouse anti-DR5 chimeric antibody has been successfully expressed in
      eukaryotic cells and shows tumoricidal activity, which establishes a foundation
      for the future research of humanized antibody medicine.

PMID- 19180919
TI  - [Metabonomic profile of urine from rats administrated with different treatment
      period of rifampin].
AB  - OBJECTIVE: To study the effect of rifampin (RFP) on the metabonomic profile of
      rat urine and its relationship with traditional toxicity evaluation of blood
      biochemical indicators and histopathology. METHODS: Thirty-six male Wistar rats
      were randomly divided into control group, 50 mg/kg RFP group, and 100 mg/kg RFP
      group, with 12 rats in each group. Rats in each group were given intragastric
      infusion with a daily dose of 0, 50 mg/kg RFP, and 100 mg/kg RFP for 3, 7, and 14
      days, respectively. Then 4 rats in each group were killed on the next day of
      administration to collect blood samples and liver sample for the determination of
      blood biochemical indicators and for the pathological analysis of the liver. The
      urine specimens over 24 hours of each rat were collected before and after each
      treatment until the rat was killed. 1H nuclear magnetic resonance (1H NMR)
      spectra of these urine specimens were acquired and subjected to data preprocess
      and principal component analyses (PCA). RESULTS: The level of serum total
      bilirubin of the rat administrated with 100 mg/(kg x d) RFP for 7 days was
      significantly higher than that of control group (P < 0.05). Mild hepatotoxicity
      to the rat, treated with RFP of higher dosage (100 mg/kg) and longer duration (14
      days), was revealed by the traditional histopathological method. The metabonomic
      spectra of rat urine in different groups differed from each other; a trajectory
      bias in determination of rat urine by 1H NMR occurred depending on the
      administration duration. As demonstrated by 1H NMR spectra of urine in rats
      treated with RFP, the concentration of urinary citrate and 2-oxoglutarate
      decreased, along with the remarkable increase of the concentrations of urinary
      taurine and glucose (compared with those of the control group). CONCLUSIONS:
      Being consistent with the results of traditional toxicity evaluation
      measurements, metabonomic method is more sensitive. The 1H-NMR metabonomic
      profile of the rat urine is closely related with the duration of RFP. The hepatic
      toxicity induced by RFP is related to the reduction of energy metabolism in
      tricarboxylic acid cycle and the perturbation of glucose and lipid metabolism.

PMID- 19180921
TI  - [Hypoxia increases the expression of heparitinase and the invasiveness through
      the hypoxia inducible factor-1alpha dependent pathway in human ovarian cancer
      cell line SKOV3].
AB  - OBJECTIVE: To investigate the heparitinase (HPA) expression and cell invasiveness
      in human ovarian cancer cell line SKOV3 during hypoxia, and explore their
      relationship with hypoxia inducible factor-1alpha (HIF-1alpha). METHODS: SKOV3
      cells were incubated with normoxia, hypoxia, and hypoxia plus rapamycin,
      respectively. SKOV3 cells of hypoxia group were incubated in 5% CO2 + 1% O2.
      Cells in hypoxia plus rapamycin group were incubated with 10 ng/ml of rapamycin
      before cultured under hypoxic condition. Cells in each group were collected for
      analysis after incubated with hypoxia for 12, 24, and 36 hours, respectively.
      Western blotting and RT-PCR were performed to detect the expressions of HIF
      1alpha and HPA. Cell invasiveness was measured by matrigel invasion assay.
      RESULTS: Western blotting showed that the expression of HIF-1alpha significantly
      increased compared with normoxic group (P < 0.05). However, hypoxia had no
      obvious impact on HIF-1alpha mRNA expression. The expressions of HPA protein and
      mRNA of SKOV3 cells of hypoxia group were significantly higher than normoxic
      group (P < 0.05). The up-regulation of HPA expression in hypoxic group decreased
      after the utilization of rapamycin. The cell invasion of hypoxic group was
      significantly higher than that of normoxic group (P < 0.05); meanwhile, the
      expression of HPA was positively correlated with the invasiveness of SKOV3 cells
      (r = 0.9863, P < 0.05). CONCLUSION: Hypoxia may promote the expression of HPA and
      the invasiveness of SKOV3 cells through the HIF-1alpha pathway, which plays an
      important role in the pathogenesis of ovarian cancer.

PMID- 19180920
TI  - [Relationship between the effect of vascular endothelial growth factor on
      epithelial-mesenchymal transition of HK-2 cells and the expressions of bone
      morphogenetic protein-7 and inhibitor of DNA binding/differentiation].
AB  - OBJECTIVE: To examine the relationship between effect of vascular endothelial
      growth factor (VEGF) on epithelial-myofibroblast transition (EMT) of HK-2 cells
      and changes in expressions of bone morphogenetic protein-7 (BMP-7) and inhibitor
      of DNA binding/differentiation (Id) 2, Id3. METHODS: The cultured HK-2 cells were
      co-treated with transforming growth factor-beta1 (TGF-beta1) (5 ng/ml) and
      VEGF165 (0.1, 1, 10, 100 ng/ml), or with TGF-beta1 (5 ng/ml) and VEGF receptor-1
      neutralized antibody (10 microg/ ml), and were also co-treated with TGF-beta1 (5
      ng/ml) and VEGF165 (100 ng/ml) with or without activin receptor-like kinase 6
      (Alk6)/Fc Chimera (2 microg/ml, to neutralize endogenous BMP-7) for 48 hours.
      mRNA and protein expressions of alpha-smooth muscle actin (alpha-SMA), E
      cadherin, BMP-7, Id2 and Id3 of HK-2 cells were assessed with double-stain
      immunocytochemistry, real-time PCR and Western blot respectively. RESULTS:
      Compared with normal controls, alpha-SMA expression significantly increased,
      while E-cadherin, BMP-7, Id2, and Id3 mRNA and protein expressions markedly
      decreased in HK-2 cells treated with TGF-beta1 (5 ng/ml) (P < 0.05). VEGF165
      interrupted TGF-beta1 induced alpha-SMA expression in a dose-dependent manner and
      upregulated BMP-7, Id2 mRNA and protein expressions of the cells (P < 0.05).
      alpha-SMA expression increased, while E-cadherin, BMP-7, and Id2 expressions
      decreased further in HK-2 cells co-treated with TGF-beta1 and VEGFR1 antibody
      compared with normal controls (P < 0.05). When endogenous BMP-7 was neutralized
      with Alk6/Fc Chimera in the cells co-treated with TGF-beta1 and VEGF165, alpha
      SMA expression upregulated (P < 0.05), while Id2 was not changed. CONCLUSIONS:
      VEGF165 may partially inhibit TGF-beta1-induced EMT of HK-2 cells in vitro. This
      effect is related to the upregulated expressions of BMP-7 and Id2. Id2 may be
      upregulated directly by VEGF165, but not related to BMP-7.

PMID- 19180922
TI  - [Further development of pulmonary artery after Glenn procedure: effect of
      different antegrade pulmonary blood flows on cyanotic congenital heart defects].
AB  - OBJECTIVE: To compare the effect of different antegrade pulmonary blood flow on
      the further development of pulmonary artery after Glenn procedure in cyanotic
      congenital heart defects (CHD) patients. METHODS: Between October 2000 and
      December 2006, 132 CHD patients with decreased pulmonary artery blood flow
      underwent bidirectional Glenn shunt, among them 18 patients received
      intraoperative lung biopsy. Patients were divided into two groups according to
      their different sources of antegrade pulmonary blood flow: antegrade arterial
      blood flow group (n = 33) and antegrade venous blood flow group (n = 99). The
      percutaneous oxygen saturation (SpO2), hemoglobin (Hb) concentration, and
      hemotocrit (Hct) value were examined and recorded before and after operation. The
      diameters of left pulmonary artery (LPA) and right pulmonary artery (RPA) were
      measured with two-dimensional echocardiography and the results were used to
      calculate the pulmonary artery index (PAI). The method of half-quantitative
      morphometric technique and an image analyzer were used to measure the following
      indicators of pulmonary microvessels: the percentage of media thickness (MT%),
      the percentage of media section area (MS%), vascular numbers of per square
      centimeter (VPSC), and mean alveolar number (MAN). RESULTS: Before the operation,
      obvious cyanosis was found in both groups, while SpO2, Hct, and Hb were not
      significantly different (P > 0.05). LPA, RPA, and PAI were not significantly
      different between two groups (P > 0.05). The MT% and MS% in antegrade venous
      blood flow group were significantly less than those in antegrade arterial blood
      flow group (P < 0.05), but VPSC and MAN were not significantly different (P >
      0.05). After Glenn procedure, hypoxia and cyanosis were remarkably improved in
      both two groups. There was a significantly negative correlation between SpO2 and
      Hct (r = -0.49, P < 0.01) or Hb (r = -0.196, P < 0.01 ). The PAI increased by 22%
      in antegrade arterial blood flow group and 44% in antegrade venous blood flow
      group (P < 0.05). The diameters of LPA and RPA in antegrade venous blood flow
      group were significantly larger than those in antegrade arterial blood flow group
      (P < 0.05) and the growth of RPA in antegrade arterial blood flow group was not
      significant. CONCLUSION: A better pulmonary artery growth occurs in the patients
      of pulmonary stenosis after Glenn shunt than in those of pulmonary atresia, and
      it contributes to an earlier completion of Fontan procedure.

PMID- 19180923
TI  - [Inductions and intubating conditions with sevoflurane and different doses of
      remifentanil without muscle relaxant in children].
AB  - OBJECTIVE: To observe the clinical effectiveness of inductions and tracheal
      intubating conditions with 3% sevoflurane and different doses of remifentanil
      without muscle relaxant in children. METHODS: Totally 120 peadiatric patients
      (aged 4-10 years, American Society of Anesthesiologists grade I for inhalational
      induction) were randomly allocated into group I (remifentanil 1 microg/kg), group
      II (remifentanil 2 microg/kg), group III (remifentanil 3 microg/kg), and control
      group (vecuronium bromide 0.1 mg/kg). After inhalational induction with 3%
      sevoflurane and 60% nitrous oxide in 40% oxygen for 2 minutes, remifentanil 1
      microg/kg, 2 microg/ kg, and 3 microg/kg were intravenously injected over 1
      minute into patients in group I , group II, and group III, respectively. After
      remifentanil administration and manual ventilation for 1 minute, the trachea was
      intubated. In the control group, 2 minutes after intravenous administration of
      vecuronium bromide 0.1 mg/kg, tracheal intubation was attempted. Agitation,
      intubating satisfactoriness, and the circulation changes after tracheal
      intubation and anesthesia induction were observed. RESULTS: In these four groups,
      agitation occurred in 37.5% of patients during sevoflurane induction.
      Satisfactory intubation rate was 70.0% in group I, 86.7% in group II, 90.0% in
      group III, and 93.3% in the control group. Compared with the control group, the
      impact of tracheal intubation on the circulatory system was smaller in group I ,
      II , and III. CONCLUSIONS: Induction with 3% sevoflurane combined with
      remifentanil can be smoothly performed, followed by the successful tracheal
      intubation. The intubating conditions are more satisfactory with 3% sevoflurane
      combined with remifentanil 2 microg/kg or 3 microg/kg.

PMID- 19180924
TI  - [Expression of prostate stem cell antigen and Claudin-4 in human pancreatic
      carcinoma].
AB  - OBJECTIVE: To investigate the expressions of prostate stem cell antigen (PSCA)
      and Claudin-4 in human pancreatic carcinoma and to discuss its role in the
      ontogenesis of pancreatic cancer. METHODS: Pancreatic carcinoma tissue microarray
      was constructed, containing 100 cores of 10 normal adult pancreas tissues, 12
      chronic pancreatitis tissues, and 78 pancreatic carcinomas. The expressions of
      PSCA and Claudin-4 were detected using immunohistochemical method and the
      relationship between PSCA and Claudin-4 and the pancreatic carcinoma was
      analyzed. RESULTS: The positive expression rates of PSCA and Claudin-4 protein in
      pancreatic carcinoma were 79. % and 88. % respectively. PSCA and Claudin-4
      staining were more intense in malignant cells than in chronic pancreatic tissues
      and normal adult pancreas tissues. No evidence was found for an association
      between expressions of PSCA and Claudin-4 and other variables, including gender,
      age at surgery, and tumor grade. CONCLUSIONS: The expressions of PSCA and Claudin
      4 are related to the pancreatic carcinomas. PSCA and Claudin-4 play a role in the
      development of pancreatic cancer, but PSCA and Claudin-4 are not correlated with
      the clinical pathology of tumor.

PMID- 19180925
TI  - [Vertigo and neurologic diseases].
AB  - Vertigo, a common clinical complaint, is closely linked with neurologic diseases.
      This article summarizes many neurologic diseases (including stroke, migraine,
      epileptic vertigo, psychiatric abnormalities, rotational vertebrobasilar
      insufficiency, and multiple sclerosis) with vertigo as one of its main symptoms,
      and introduces the diagnostic methods of vertigo.

PMID- 19180926
TI  - [Clinical update on non-surgical management of vertigo].
AB  - The incidence of vertigo increases with both aging and changing lifestyles among
      Chinese. Apart from well established medical and surgical treatment, a number of
      non-surgical treatment modalities have been available recently.

PMID- 19180927
TI  - [Neuronal plasticity of otolith-related vestibular system].
AB  - This review focuses on our effort in addressing the development and lesion
      induced plasticity of the gravity sensing system. After severance of sensory
      input from one inner ear, there is a bilateral imbalance in response dynamics and
      spatial coding behavior between neuronal subpopulations on the two sides. These
      data provide the basis for deranged spatial coding and motor deficits
      accompanying unilateral labyrinthectomy. Recent studies have also confirmed that
      both glutamate receptors and neurotrophin receptors within the bilateral
      vestibular nuclei are implicated in the plasticity during vestibular compensation
      and development. Changes in plasticity not only provide insight into the
      formation of a spatial map and recovery of vestibular function but also on the
      design of drugs for therapeutic strategies applicable to infants or vestibular
      disorders such as vertigo and dizziness.

PMID- 19180928
TI  - Medicare advantage and Medigap serve key populations.

PMID- 19180929
TI  - Lawmakers get big picture on pharmacy issues.

PMID- 19180930
TI  - What the doctor ordered. Health plans take steps to ensure members adhere to
      their medication regimens.

PMID- 19180931
TI  - Do no harm. AHIP coverage presents a special report on health plan efforts to
      reduce the incidence of medical errors by triggering systemic change in health
      care.

PMID- 19180932
TI  - Preventing the preventable. Health plans implement high-tech and low-tech
      solutions aimed at reducing hospital medication errors.

PMID- 19180933
TI  - Culture of safety. Health care stakeholders overwhelmingly unite around safety
      incentives as a means to prevent medical errors.

PMID- 19180934
TI  - Special care. Specialty pharmacy programs address patients' many needs.

PMID- 19180935
TI  - Quality first. Private sector initiatives inform government effort to control
      escalating use of high-tech diagnostic imaging.

PMID- 19180936
TI  - Out of the office and onto the Web.

PMID- 19180937
TI  - Promoting a cultural shift and a system change to respond to agitated and
      excessive behaviours (REAB).
AB  - The Responding to Excessive & Agitated Behaviour (REAB) Program was designedas a
      system change model to create a healthy work culture and to promote quality,
      client-centered care. It is a unique program that has integrated best clinical
      practices with workplace safety policy and criteria promoting continuous
      assessment ofa facility's ability to meet the requirements of the REAB model.
      Funding was received from the BC Nursing Directorate. Key clinical and work
      health leaders in a large BC health authority were supportive of this initiative.
      Phase I began in 2004 with a review of the literature and environmental scans
      leading to the development of the REAB model. The model contains ten elements
      which if addressed promotes the best in clinical practice and working conditions.
      In Phase II benchmarking data were collected and the REAB process was trialed in
      fifteen facilities. The findings and the model were validated by a variety of
      representatives from practice and industry in a one day forum. Phase III was the
      development of a resource toolkit to guide the implementation process and
      contained supportive resources. Phase IV, now in progress, consists ofan
      orientation to the toolkit and access to a facilitator who assists agencies in
      identifying their own gaps in relation to the model, as wellas guides the
      implementation of a viable and sustainable plan for improvement. This paper
      reviews the evolution and the development of this project so that others may
      incorporate its methodology and resources into their own facility.

PMID- 19180938
TI  - A high-tech way of teaching gerontological content to undergraduate nursing
      students.

PMID- 19180939
TI  - Continence in the community.

PMID- 19180940
TI  - Efficacy vs. effectiveness--the case for clinical expertise.

PMID- 19180941
TI  - The 2008 Gold Medal for Distinguished Service--Dr. Sam W. Rogers, Jr.

PMID- 19180942
TI  - Root caries--A review of the etiology, diagnosis, restorative and preventive
      interventions.

PMID- 19180943
TI  - The Texas Dental Journal 125 years and counting. The quasquicentennial
      anniversary of America's oldest dental periodical.

PMID- 19180944
TI  - How to attract the "right" new patients to your practice.

PMID- 19180945
TI  - "Restoratively driven papilla regeneration: correcting the dreaded 'black
      triangle'".
AB  - Until now there were very few dedicated tools or techniques for restoratively
      driven papilla regeneration. Previous attempts at both diastema closure and
      papilla regeneration using direct composites often ended with significant
      compromise in periodontal health. The interdental papilla serves as both an
      esthetic and functional asset, and anatomically ideal interproximal composite
      shapes can serve as a predictable scaffold to regain this valuable gingival
      architecture. The reader is strongly cautioned that to attempt this elective
      procedure using no magnification and without appropriate materials may not be in
      the patient's best interest, and that non treatment or referral is recommended.
      This extremely rounded, injection molded composite filling technique is new. Once
      again, technological advancements allow changes to perform techniques that were
      previously unthinkable. Slowly, the profession will change their thought
      patterns, retrain their hands and minds, and allow this substantial clinical
      evolution in restorative dentistry.

PMID- 19180946
TI  - Oral and maxillofacial pathology case of the month. Odontogenic myxoma.

PMID- 19180947
TI  - [Tissue culture and rapid propagation of Phytolacca americana].
AB  - OBJECTIVE: To explore the technique of rapid propagation for Phytolacca
      americana. METHODS: Aseptic seedling were used as explants. RESULTS: The best
      explants were the stems from strong aseptic seedling. The optimal culture media
      were MS + NAA (0.2 mg/L) +6-BA (1.0 mg/L) for primarily culture, MS + NAA (0.2
      mg/L) +6-BA (2.0 mg/L) for the induction of clustered shoots 1/2MS with NAA 0.4
      mg/L for rooting. CONCLUSION: The propagating coefficient of Phytolacca americana
      can be improved by inducing the clustered shoots from aseptic seedling.

PMID- 19180948
TI  - [Analysis of Paeonia lactiflora by X-ray diffraction Fourier pattern method].
AB  - OBJECTIVE: To establish a new method for identification and analysis of
      traditional Chinese medicine root of herbaceous peony. METHODS: Powder X-ray
      diffraction Fourier fingerprint pattern was used. RESULTS: Experiments and
      analysis were carried out on 6 kinds of roots of traditional Chinese medicines
      herbaceous peony. The standard X-ray diffraction Fourier fingerprint pattern and
      characteristic diffraction peaks of Paeonia lactiflora were obtained. CONCLUSION:
      The results indicates this method can be used for the idetification of Paeonia
      lactiflora.

PMID- 19180949
TI  - [The microscopical and HPLC identification of several" Muxiang" raw materials].
AB  - OBJECTIVE: To differentiate and identify several species of "Muxiang". METHODS:
      The main microscopic features and HPLC chromatograms of diagnostic components
      were studied. RESULTS: Distinguishable characters were found in two methods.
      CONCLUSION: The results provide reliable and simple reference for the
      authentication of raw materials of" Muxiang" species, especially the toxic
      species.

PMID- 19180950
TI  - [Chemical constituents of Solanum cathayanum].
AB  - OBJECTIVE: To study the chemical constituents of Solanum cathayanum. METHODS:
      Chemical constituents were isolated by chromatographic methods and identified by
      NMR analysis. RESULTS: Five compounds were isolated and identified as lignoceric
      acid (I), beta-sitosterol (II), lupeol (III) 8-hydroxy-3-methoxy-5H-pyrido [2, 1
      c] pyrazin-5-one (IV), ethly 2,6-dioxo-1,2,3,6-tetrahy-dropyrimidine-4
      carboxylate (V). CONCLUSION: Compound I and III are isolated from this plant for
      the first time. Compound IV and V are isolated from the genus of Solanum for the
      first time.

PMID- 19180951
TI  - [Studies on the constituents from the herba of Erigeron acer].
AB  - OBJECTIVE: To investigate the chemical constituents of the aerial part of
      Erigeron acer. METHODS: The chemical constituents were isolated by various
      columns and thin layer chromatographic methods. The structures were identified by
      spectral data. RESULTS: Five compounds were isolated and identified as alpha
      amyrin (1), beta-amyrin (2), caffeic acid (3), quercetin (4), 4'-hydroxywogonin-7
      O-beta-D-glucuronic acid glycoside (5). CONCLUSION: The five compounds are
      obtained from this plant for the first time. The signals of 13C-NMR of the
      compound(5) are reassigned by means of DEPT, HMQC, HMBC, the signals of 1H-NMR of
      2" - 5"-H of the glucuronic acid moiety are assigned by means of HMBC, HMQC, 1H
      1H COSY for the first time.

PMID- 19180952
TI  - [Determination content of the antidepressant extraction and analysis the trace
      elements from Morinda officinalis].
AB  - OBJECTIVE: To study on the antidepressive extraction and determinated the content
      of the oligosaccharides I , the proteins and the trace elements from Morinda
      officinalis. METHODS: We analyzed the content of the total oligosaccharides, the
      proteins and the trace elements by Phenol-Sulferic acid, Coomassie brilliant blue
      and inductive coupling plasm atomic emission spectrometer (ICP-AES) methods,
      respectively. RESULTS: The percent of the oligosaccharides and the proteins were
      89.4% and 0.19% in the extraction from M. officinalis, respectively. The total
      actively oligosaccharides I were subjected to the D-941 ion column chromatography
      to give the extraction in which hardly and protein were determined. 12 kinds of
      trace element including Zn, Fe, Ca ect. in the extraction (the oligosaccharides
      I) were determined by ICP-AES without the noxious trace elements including As,
      Cd, Pb ect. CONCLUSION: The antidepressive activity extraction(the
      oligosaccharides I ) was a highly pure and vegetal oligosaccharides.

PMID- 19180953
TI  - [Studies on the chemical constituents of Rabdosia rubescens].
AB  - OBJECTIVE: To study the chemical constituents from Rabdosia rubescens. METHODS:
      Compounds were isolated by Silica gel,Sephadex LH-20 and ODS column
      chromatographies, their strctures were identified by physicochemical property and
      NMR, MS. RESULTS: Eight constituents were identified as phaeophytin a (1),
      phaeophytin b (2), 17c-ethoxypheaophorbide a (3), 17c-ethoxyphea ophorbide b (4),
      oleanolic acid (5), physcion (6), emodin-8-O-beta-D-glucopyranoside (7),
      isorhamnetin (8). CONCLUSION: Compounds 1-4, 6 and 7 are obtained for the first
      time from this plant.

PMID- 19180954
TI  - [Studies on the anti-tumor activity principles of a marine-derived fungus BZYT
      21].
AB  - OBJECTIVE: To study the chemical constituents of a marine-derived fungus
      possessing anti-tumor activity. METHODS: The compounds were isolated by various
      chromatographic methods and their structures were elucidated through
      spectroscopic analysis and chemical and physical properties. RESULTS: Nine
      compounds were isolated and identified as: (S)-(-)-N-benzoylphenylalaninol,
      asperphnamate, cerevisterol, (22E, 24R)-6beta-methnoxyergosta-7,22-diene-3beta,
      5alpha-diol, (22E, 24R)-5alpha, 6alpha-epoxy-ergosta-8, 22-diene-3beta, 7alpha
      diol, (22E, 24R) -3beta, 5alpha, 9alpha-trihydroxyergosta-7, 22-diene-6-one,
      (22E, 24R) -3beta-hydroxy-ergosta-5, 8, 22-trien-7-one, ergosterol, ergosterol
      peroxide. CONCLUSION: (22E, 24R)-3beta-hydroxy-ergosta-5, 8, 22-trien-7-one is
      isolated from microorganisms for the first time.

PMID- 19180955
TI  - [Studies on chemical constituents of Salacia prinoides].
AB  - OBJECTIVE: To study the chemical constituents of Salacia prinoides. METHODS: The
      chemical constituents were isolated and purified with various column
      chrmoatography and the structures were elucidated by chemical evidence and
      spectral analysis. RESULTS: Sixteen compounds,including seven triterpenes :
      lupeol (1), Lup-20(29)-en-3beta,30-diol (2), 30-Hydorxylup-20 (29) -en-3-one (3),
      3, 22-dioxo-29-normoretane (4), Ursolid acid (5), beta-Sitosterol (6), beta
      Daucosterol (7); Four flavanoids: Quercetin (8), Quercet-in-3', 4'-dimethylether
      (9), Isorhamnetin (10), Kaempferol-4'-methylether (11); Three Phenolic
      acids:Gallic acid (12), Ethyl gallate (13), Egallic acid (14); Two Fatty series:
      Hentriacontanol (15), Hentriacontan-12-ol (16) were obtained from the titled
      plant. CONCLUSION: -4, 8 - 13 are isolated from the genus for the first time, 5,
      14 -16 are isolated from the plant for the first time.

PMID- 19180956
TI  - [Studies on the triterpenes from loquat leaf (Eriobotrya japonica)].
AB  - OBJECTIVE: To investigate the chemical constituents from Loquat leaf (Eriobotrya
      japonica). METHODS: Compounds were isolated by a combination of silica gel and
      ODS column chromatographies and preparative TLC and HPLC, their structures were
      identified by chemical and spectral methods. RESULTS: Nine triterpenes were
      isolated and identified as methyl betuliate (I), oleanolic acid (II), ursolic
      acid (III), methyl maslinate (IV), methyl corosolate, (methyl 2alpha-3alpha
      dihydroxyurs-12-en-28-oate, V), maslinic acid (VI), corosolic acid (VII),
      tormentic acid (VIII), euscaphic acid (IX) from loquat leaf. CONCLUSION:
      Compounds I and V are obtained from this plant and Eriobotrya genus for the first
      time.

PMID- 19180957
TI  - [Studies on the antioxidant activities of leaves from Senecio argunensis].
AB  - OBJECTIVE: To study antioxidant activities of different extracts of Senecio
      argunensis. METHODS: The antioxidant activities of S. argunensis extracts with
      acetoacetate, n-Butanol and water were detected by DPPH * free radical-scavenging
      method and beta-carotene/linoleic acid system. RESULTS: The acetoacetate, n
      Butanol and water extracts from S. argunensis eliminated DPPH * in dose-dependent
      manner, their EC50 values were 0.0198, 0.0219 and 0.092 mg/ml, respectively. The
      strength order of the antioxidant activities of the three parts in beta
      carotene/linoleic acid system was acetoacetate, n-Butanol and water extracts.
      CONCLUSION: The extracts of the three parts of S. argunensis all have antioxidant
      activities. Among these extracts, extracts with acetoacetate have the highest
      antioxidant activity.

PMID- 19180958
TI  - [Studies on the effect of Ginkgo biloba extracts on NF-kappaB pathway].
AB  - OBJECTIVE: To investigate NF-kappaB and IkappaBalpha activities in HL-60 induced
      by TNF-alpha in order to understand the molecular mechanism of GbE in asthma
      treatment. METHODS: The amount of IkappaBalpha in HL-60 cells stimulated by TNF
      alpha and GbE was measured by western blotting. Plasmid pNF-kappaB-LuC was
      transfected and NF-kappaB activity was analyzed by measuring the expression level
      of luciferase. RESULTS: It showed in the luciferase assay that the activity of NF
      kappaB could significantly be suppressed in HL-60 cells after the pretreatment
      with CGbE. However, the phosphorylation and subsequent degradation of IKBalpha
      induced by TNF-alpha can not be inhibited in HL-60 cells even we prolonged the
      treatment time or increased the concentration of GhE. CONCLUSION: GhE can
      suppress the NF-kappaB gene expression actively on independent of NIK/ IKK/
      IkappaBalpha pathway in HL-60 cells.

PMID- 19180959
TI  - [Effects of Xiaoyao Wan on the behavioral despair and stress depression mice].
AB  - OBJECTIVE: To investigate the anti-depressant effect and the possible mechanism
      of Xiaoyao Wan in animal models. METHODS: The open-field test and the forced
      swimming test were applied to study the anti-depressant effect of Xiaoyao Wan in
      mice, and HPLC-ECD was carried out to assay the contents of 5-HT and 5-HIAA, and
      the mechanism of Xiaoyao Wan on anti-depressant effect was discussed. RESULTS:
      Xiaoyao Wan at the dose of 200, 400 and 600 mg/kg significantly increased the
      revolutions in force swimming test, and ameliorated brain cortex 5-HT and 5-HIAA
      content of restraint mice. But there was no effect on brain cortex 5-HT and 5
      HIAA content of non-restraint mice. CONCLUSION: Xiaoyao Wan has significant anti
      depressant effect which may be related to the potentiation of brain serotonergic
      function.

PMID- 19180960
TI  - [The hepatoprotective effect of aqueous extracts from Ficus hirta on N, N
      dimethylformamide induced acute liver injury in mice].
AB  - OBJECTIVE: To investigate the effect of aqueous extract from Ficus hirta on N, N
      Dimethylformamide (DMF) induced liver injury in mice. METHODS: C57BL/6 mice and
      ICR mice were randomly divided into 5 groups: negative control group, positive
      control group and three treated groups respectively. Treated groups were
      administered orally with 100, 200, 300 g/kg Ficus hirta aqueous extract per day
      respectively for 5 days. On the 4th day, 2. 3 g/kg DMF was given by
      intraperitoneal injection to all C57BL/6 mice except negative control group,
      while for ICR, DMF was administration at a 2.75 g/kg dose. 48h after DMF
      injection, serum samples were collected to determine the activities of ALT, AST
      and LDH and the pathological changes of liver tissue were analyzed under
      microscope. RESULTS: Compared with the positive control, the activities of ALT,
      AST and LDH were significantly reduced and the liver injury obviously attenuated
      in treated groups. CONCLUSION: The aqueous extract of Ficus hirta has an obvious
      protective effect against DMF-induced acute liver injury in mice.

PMID- 19180961
TI  - [The anti-tumour effect of Wuxing soup and its mechanism in inducing apoptosis of
      tumour cells mediated by calcium].
AB  - OBJECTIVE: To confirm the anti-cancer effect and mechanism of Wuxing soup.
      METHODS: Inhibition of cellular growth under Wuxing soup treatment was observed
      by MTT; Apoptosis was detected by gel electrophoresis, transmission electron
      microscopy and FACS; The concentration of calcium was measured by fluorescence
      probe. RESULTS: After SGC-7901 cell being treated by Wuxing soup, it showed that:
      1) Wuxing soup could specifically inhibit cancer cells proliferation in a time
      and dose dependent manner; 2) Typical apoptotic morphological changes and DNA
      ladder of SGC-7901 cells were observed; 3) calcium inhibitor Bapta AM could
      reduce the apoptotic rate and protect SGC-7901 cells in a dose dependent manner.
      CONCLUSION: Wuxing soup has an effective inhibition on cancer cells, and can
      induce SGC-7901 cells to apoptosis by calcium.

PMID- 19180962
TI  - [Neuroprotective effects of water extracts of American Ginseng on SH-SY5Y cells
      apoptosis induced by Abeta25-35].
AB  - OBJECTIVE: To study the neuroprotective effect of water extracts of American
      Ginseng (WEAG) on Abeta25-35-induced SH-SY5Y cells apoptosis in Alzheimer's
      Disease cellular model. METHODS: The optimal concentration and treating time of
      Abeta25-35 for Alzheimer's Disease cellular model as well as those of WEAG were
      measured by flow cytometer. In addition, the cell viability was measured by MTT
      test and the morphology of SH-SY5Y cells was observed by Hoechst 33258 staining.
      RESULTS: Treated by Abeta25-35 50 micromol/L 72 h later, SH-SY5Y cells turned
      rounder, aggregated and were positively stained with fluorochrome Hoechst 33258.
      Cells displayed a typical sub-diploid peak in flow cytometry, and the percentage
      of apoptosis reaches (37.30 +/- 0.69)% (P < 0.05 as compared with the control
      group) (1.56 +/- 0.80)%. When incubated with Abeta 50 micromol/L and different
      doses (0.5, 1, 5 mg/ml) of WEAG for 72h, the characteristics of apoptosis as
      measured by FCM dose-dependently declined to (16.71 +/- 1.08)%, (10.52 +/- 2.11)%
      and (3.39 +/- 1.65)%, respectively (P < 0.05 as compared with the model group).
      CONCLUSION: Water extracts of American Ginseng have markedly neuroprotective
      effects on SH-SY5Y cells apoptosis induced by Abeta25-35.

PMID- 19180963
TI  - [Rhodiola sachalinensis suppresses T241 fibrosarcoma tumor cells proliferation in
      vitro and growth in vivo].
AB  - OBJECTIVE: To study the anticancer activity of Rhodiola sachalinensis in vitro
      and in vivo experiments. METHODS: The effect of Rhodiola sachalinensis extracts
      at various concentrations on T241 fibrosarcoma cells proliferation and cytotoxic
      potential were measured. We divided T241 fibrosarcoma-bearing C57Bl6/J mice into
      two groups, the tumor inhibition rate were observed. RESULTS: Rhodiola
      sachalinensis extracts inhibited T241 tumor cells growth in a dose-dependent
      manner. The concentrations of Rhodiola sachalinensis extracts from 50 microg/ml
      to 250 microg/ml did not reduced the survival rate of T241 tumor cells. The daily
      administration of Rhodiola sachalinensis resulted in a significant suppression of
      the growth of primary tumors, compared to control group, tumor inhibition rate in
      Rhodiola sachalinensis group reached 70.9%. CONCLUSION: Rhodiola sachalinensis
      can inhibit T241 tumor cells growth and does not cause a direct cytotoxicity
      against tumor cells in vitro and in vivo.

PMID- 19180964
TI  - [Effect of fenghuaqianqingcha on experimentally induced prostatic hyperplasia in
      mice].
AB  - OBJECTIVE: To investigate the improvement of fenghuaqianqingcha (FQC) on Benign
      prostatic hyperplasia (BPH) in mice and the related mechanism. METHODS: The BPH
      model was established by subcutaneous injection of testosterone propionate in
      mice. At the same time, mice were infused into the stomach with FQC in different
      dosages for three weeks. The mice were sacrificed later, and the prostate index,
      prostatic wet weight, testosterone levels in plasma and MDA contents, NO levels,
      GSH levels, as well as oxygen radical absorbance capacity (ORAC) values in
      prostate were measured and the morphological change of prostatic gland was
      observed by light microscope to observe the effects of FQC on BPH in mice. And
      the effect of FQC on 5 alpha-reductase was determinated in vitro by HPLC.
      RESULTS: Compared with the BPH model group, all parameters including prostatic
      index, prostatic wet weight, T levels, MDA contents, ORAC values et. in different
      experimental groups showed significantly improvement after treatment with FQC.
      And FQC could inhibit the activity of 5alpha-reductase in vitro significantly.
      CONCLUSION: FQC has antagonistic effect on BPH induced by testosterone propionate
      in mice, which may involve its inhibition of the activity of 5 alpha-reductase
      and accommodate the peroxidation condition.

PMID- 19180965
TI  - [Research on the effect of phenylethanoid glycosides (PEG) of the Cistanche
      deserticola on anti-aging in aged mice induced by D-galactose].
AB  - OBJECTIVE: To investigate the effect of Phenylethanoid glycosides (PEG) of the
      Cistanche deserticola on anti-aging in aged mice induced by D-galactose. METHODS:
      Taking Vitamin E as the positive control, after administration of high and low
      dose of the PEG, detected the learning and memory ability, the activities of SOD,
      the content of MDA and organ index. RESULTS: Compared with the model group, the
      abilities of learning and memorizing were improved in PEG groups. The activity of
      SOD was enhanced significantly in serum and brain. The MDA content of liver and
      serum was decreased. The PEG also improved the Index of spleen and thymus.
      CONCLUSION: The PEG of Cistanche deserticola can enhance the ability of learning,
      memorizing, anti-oxidation, and improve immune function.

PMID- 19180966
TI  - [In vitro experimental study on the effect of resveratrol against several kinds
      of respiroviruses].
AB  - OBJECTIVE: To observe the cytopathogenic inhibitory effect of resveratrol on vary
      respiroviruses and explore the mechanism of resveratrol against viruses. METHODS:
      MDCK, A549, HEp-2 cell and MRC-5 were infected with Influenza virus type A FM1
      strain, rhinovirus type R14, RS virus, AD virus type 7 separately, and the
      antiviral activity of resveratrol were observed. RESULTS: Resveratrol
      significantly inhibited cytopathogenic effect of AD virus type 7 at the
      concentration 120 microg/ml. No significant cytopathogenic effect of Resveratrol
      inhibiting Influenza virus type A FM1 strain, Rhinovirus type R14, RS virus on
      separate cells was observed. CONCLUSION: It is concluded that resveratrol is
      effective on inhibiting AD virus type 7 in vitro, however, its mechanism is
      needed for further study.

PMID- 19180967
TI  - [Effect of capsule of Shenshuai Yangzhen on malnutrition rats with chronic renal
      failure by 5/6 nephrectomy].
AB  - OBJECTIVE: To investigate the effects of capsule of Shenshuai Yangzhen, a
      preparation of traditional Chinese medicine, on malnutrition rats with chronic
      renal failure (CRF). METHODS: SD rats received 5/6 nephrectomy for preparation of
      CRF models, and fed 4% casein at the same time. Observed when malnutrition began.
      Those consistents with malnutrition of CRF condition were randomized into model
      control group, Ketosteril group, Shenshuai Yangzhen group, and normal control
      group. After 4-weeks treatment as indicated, The blood parameters, like blood
      serum albumin (ALB), type-1 insulin like growth factor (IGF-1), total cholesterol
      (TC), triglyeride (TG), urea nitrogen (BUN), serum creatinine (Scr), haemoglobin
      (Hb), 24 hour urineprotein (24hUpr) and weight were determined. Nephrotic tissue
      was observed by microscope (included HE and PAS). RESULTS: Malnutrition situation
      in CRF rats began at the end of 10-weeks. After 4-weeks treatment, weight in
      Shenshuai Yangzhen group were higher significantly (P < 0.05). Compared with
      model control group, blood serum BUN (P < 0.05), SCr (P < 0. 05) and 24h Upr (P <
      0.001) in Shenshuai Yangzhen group were significantly lower with substantially
      elevated blood serum ALB, Hb, IGF-1 (P < 0.01; P < 0.001; P < 0.001,
      respectively). Pathology of Shenshuai Yangzhen group was a meliorated
      significantly after treated. CONCLUSION: Capsule of Shenshuai Yangzhen has a
      possible therapic effect on improving malnutrition in rats with renal
      insufficiency.

PMID- 19180969
TI  - [Effects of Panax notoginseng saponins on antioxidation and preventing DNA damage
      caused by hydroxyl radical].
AB  - Scavening effects of panax notoginseng saponins on active oxygen species in the
      systems of Fenton reaction, autoxidation of pyrogallol and riboflavine
      photosensitization were investigated by the mean of spectrophotometry. The
      inhibition of panax notoginseg saponins on the damage of DNA chain induced by
      hydroxyl radical by panax notoginseng saponins was observed by the mean of gelose
      gel electrophoresi and thiobartital spectrophotometry. The results showed that
      panax notoginseng saponins could scaven * OH, O2*- efficiently and protect DNA
      chains from being damaged by hydroxyl radical.

PMID- 19180968
TI  - [Effect of supplement energy and nourish lung herbs on drug-resistance lung
      cancer with mechanisms of mitochondrial and caspase signal].
AB  - OBJECTIVE: To explore the effect of supplement energy and nourish lung (SENL)
      herbs on the growth of drug-resistance lung cancer cells, expression of multidrug
      resistance-associated protein (MRP) and mechanisms of mitochondrial and Caspase
      signal. METHODS: Drug-resistance lung cancer cell line SW1573/2R120 was treated
      with SENL herbs and Adriamycin. Cellular toxicity with MTT colorimetric assay,
      expression of MRP protein with flow microscopy, the fluorescence intensity of
      mitochondria membrane potetional and Ca2+ with laser confocal microscopy, the
      activities of caspase-3 and caspase-8 with colorimetric assay were detected.
      RESULTS: Compared with control group, cellular inhibitory rate was increased
      obviously, expression of MRP protein was decreased, mitochondria membrane
      potetional and intracellular Ca2+ were decreased, the activities of caspase-3 and
      caspase-8 were increased in the group of SENL herbs. CONCLUSION: SENL herbs can
      interfere and reverse drug resistance in lung cancer by the mechanism of
      decreasing mitochondria membrane potetional and increasing the activities of
      caspase-3 and caspase-8.

PMID- 19180970
TI  - [Thyroid-induced hyperthyroidism Yin-deficiency model of rats].
AB  - OBJECTIVE: To establish a rat model of hyperthyroidism Yin-deficiency. METHODS:
      SD rats separate male and female were randomly divided into four groups, a total
      of eight groups, each with six. The first group for the control group, 2 to 4 for
      the experimental drug-treated group, including thyroid-low, medium and high-dose
      group. In addition to the first group lavage volume of saline, the other groups
      were given the concentration of 2. 5, 5, 10 mg/kg-saline suspension of the
      thyroid. Once a day, 30 days for delivery. RESULTS: Compared with the control
      group, with the exception of Group 4 female rats serum T3, T4, FT3, FT4 values
      were significantly higher (P < 0.01), serum TSH was significantly lower (P <
      0.05), the other treatment groups had different values no significant difference
      (P > 0.05). Group 4 that female rats modeling was success. CONCLUSION:
      Administration of thyroid-Suspension 10 mg/ kg for 30 d, female rats
      hyperthyroidism Yin-deficiency rat model is success.

PMID- 19180971
TI  - [Influencing factors in preparation of brucine liposomes by ammonium sulfate
      transmembrane gradients].
AB  - OBJECTIVE: To study the influencing factors in preparation of brucine liposomes
      by ammonium sulfate transmembrane gradients. METHODS: The brucine liposomes were
      separated by Sephadex G-50, and the influence of various factors on the
      entrapment efficiencies were investigated. RESULTS: The entrapment efficiency was
      enhanced by increased ammonium sulfate concentration, ethanol volume and PC
      concentration. CONCLUSION: Burcine liposomes prepared by ammonium sulfate
      transmembrance gradients can get a high entrapment efficiency, the main
      influencing factors were ammonium sulfate concentration, ethanol volume and PC
      concentration.

PMID- 19180972
TI  - [Study on preparation technology of aconitine liposomes].
AB  - OBJECTIVE: To optimize the prescription and preparation of aconitine liposomes.
      METHODS: Aconitine liposomes were prepared by ethanol injection method. The
      encapsulation efficiency was taken as inspection target and the preparation of
      liposomes were optimized by orthogonal design. HPLC was used to measure the
      encapsulation efficiency. RESULTS: The best prescription was aconitine/
      lecithin/cholesterol( 1: 15: 5)with phosphate buffer solution (pH 7. 4) as
      hydration media. The hydration temperature was 60 degrees C. CONCLUSION: The
      optimized formulation of aconitine liposomes is reasonable in prescription,
      practicable in technology, high in encapsulation efficiency and good in
      stability.

PMID- 19180973
TI  - [Comparison study of different extraction methods of Sarcandra glabra].
AB  - OBJECTIVE: To compare the different extraction methods of Sarcandra glabra
      (Thunb.) Nakai. METHODS: To compare the yield of extraction and determination
      content of extraction by 6 kinds of different extraction methods as cold-soaked
      extraction, percolation extraction, reflux extraction, continuous reflux
      extraction, ultrasonic extraction and microwave extraction, and the content of
      furmaric acid was determinated as index. RESULTS: The yields of extraction and
      contents of availability component were very different through 6 kinds of
      different extraction methods. Among them, the yields of reflux extraction and
      continuous reflux extraction were higher, the contents of availability components
      of ultrasonic extraction and microwave extraction were higher. CONCLUSION:
      Microwave extraction method is better than other methods. It is fast economical,
      solvent and energy, and also has higher yield of availability component.

PMID- 19180974
TI  - [Studies on separation and purification of total saponin from flower buds of
      Panax notoginseng by macroporous resins].
AB  - OBJECTIVE: To optimize the technical parameters of separation and purification of
      total saponin from flower buds of Panax notoginseng by macroporous resins.
      METHODS: Based on absorptive capacity and elution efficiency of total saponin
      from flower buds of Panax notoginseng, the best type of resin and the conditions
      to separate and purify total saponin by macroporous resins were optimized.
      RESULTS: The AB-8 resin was chosen, washed with 3 BV of 70% ethanol, and with the
      absorption and elution velocity of flow 2BV/h. The optimal concentration of the
      raw material was 0. 2 g/ml. The purity of total saponin obtained was 87.60%.
      CONCLUSION: Using AB-8 resin to separate and purify total saponin from flowers of
      Panax notoginseng is feasible.

PMID- 19180975
TI  - [Study on extraction and property testing of pastern from mesona blume].
AB  - OBJECTIVE: In order to find out the pastem's content and property. METHODS: The
      colloid substances-pastem were extracted from the grass with high pressure and
      high temperature and then were compared. RESULTS: The pastem's average content
      was 30. 55 g/100 g. The average intrinsic viscosity of pastem was 85.01 ml/g.
      Using the cassava starch complex gums as a standard reference, the coefficient of
      hardness, elastic coefficient and coefficient of cohesion were 23.71, 1.128,
      0.431, respectively. CONCLUSION: This study provides the theory basis of setting
      quality standard of country, and helps to develop the pastem's prodution.

PMID- 19180976
TI  - Genetic testing for health care purposes, a Council of Europe Protocol.

PMID- 19180977
TI  - Testing the margin of appreciation: therapeutic abortion, reproductive 'rights'
      and the intriguing case of Tysiqc v. Poland.
AB  - In Tysiac v. Poland (2007) the Strasbourg Court ruled in favour of the applicant
      (who had been denied access to a lawful therapeutic abortion), finding that
      Poland had failed to comply with its positive obligations to safeguard the
      applicant's right to effective respect for her private life under Article 8.
      Exploring this controversial judgment, the author assesses the claim that Tysiac
      marks a 'radical shift' on the part of the Court in creating a 'right to
      abortion'. The author argues that while Tysiac makes an important addition to
      abortion jurisprudence, the notion it founds such a 'right' greatly overstates
      the legal significance of this case.

PMID- 19180978
TI  - Withdrawing from participating in a biobank--a comparative study.
AB  - The development of biobanks worldwide is considered to hold great promise for the
      provision of new insights into the connection between genes and environment and
      to have a positive impact on public health. There is, however, a constant tension
      between the rights of individuals on one hand and the progress of research on the
      other hand. One of the rights developed to protect the autonomy and free will of
      participants and reflecting the basic principles regulating medical research
      according to the Nuremberg Code and the Declaration of Helsinki is the right to
      be able to withdraw from the biobank at any time as an expression of the
      participant's free will and autonomy. There are two important problems to
      withdrawing, namely the 'what' and 'when'--what can be withdrawn and when can it
      be withdrawn.

PMID- 19180979
TI  - Stimulating research and development of pharmaceutical products for neglected
      diseases.
AB  - This article provides an introduction to the problem of pharmaceutical research
      and development of medicinal products for neglected diseases in developing
      countries. The prevailing market-based intellectual property incentive model of
      global pharmaceutical innovation has focussed health research priorities mainly
      on needs of industrialized countries. Increased international attention to the
      lack of health tools to prevent or treat diseases affecting impoverished regions
      has raised the discussion on how to encourage sustainable innovation in this area
      with little or no market. Proposals include models such as for example prize
      funds, advanced purchase commitments patent pools or creative licensing
      strategies and seek to complement the current intellectual property based
      incentive mechanism and government's innovation policy instruments such as tax
      credits or public research funds. Indispensable requirement to tackle the issue
      of neglected diseases, however, is a concerted commitment of all stakeholders on
      national and international levels.

PMID- 19180980
TI  - Can I decide please? The state of children's consent in the UK.
AB  - The right to self-determination for those with adequate competence underpins a
      democratic society. The European Convention on Human Rights does not draw a
      distinction between adults and children in this respect, and in fact advances the
      concept of children's rights. However in the UK a combination of statute and case
      law places some constraints on a child's right to autonomy. Prior to the Gillick
      principle there was little guidance on managing children under the age of
      sixteen. Whilst this is much clearer now there are some anomalies, for instance
      is the right to refuse the same as the right to agree to surgery? The increasing
      'rights culture' for children is bringing this issue before the Courts more and
      more and the status of children continues to evolve in the UK.

PMID- 19180981
TI  - European Court of Human Rights. ECHR 2008/13 case of N. v. The United Kingdom, 27
      May 2008, no. 26565/05 (Grand Chamber).

PMID- 19180982
TI  - European Court of Human Rights. ECHR 2008/14 Case of I v. Finland, 17 July 2008,
      no. 20511/03 (Fourth section).

PMID- 19180983
TI  - European Court of Human Rights. ECHR 2008/15 Case of Salmanov v. Russia, 31 July
      2008, no. 3522/04 (First Section).

PMID- 19180984
TI  - European Court of Justice. ECJ 2008/11 Commission of the European Communities v.
      Federal Republic of Germany, 11 September 2008 (C-141/07).

PMID- 19180986
TI  - Council of Europe. Additional Protocol to the Convention on Human Rights and
      Biomedicine, concerning genetic testing for health purposes.

PMID- 19180985
TI  - European Court of Justice. ECJ 2008/12 Sot. Lelos kai Sia EE and Others v.
      GlaxoSmithKline AEVE Farmakeftikon Proionton, 16 September 2008 (Joined cases C
      486/06 to C-478/06).

PMID- 19180987
TI  - Effects of lipopolysaccharide endotoxin on the insulin-like growth factor I
      system in rats with cirrhosis.
AB  - BACKGROUND: Patients with liver cirrhosis have disturbances in the insulin-like
      growth factor I (IGF-I) system that favour insulin resistance and catabolism.
      High morbidity and mortality of such patients from infections may be related to
      further aggravation of this problem but human data are controversial. Here, the
      effect of lipopolysaccharide (LPS) endotoxin on the IGF system was studied in
      rats with cirrhosis. MATERIALS AND METHODS: One month after induction of
      cirrhosis by bile duct ligation, LPS was administered (0.5 mg/kg) and the IGF
      system assessed 24 h later. Sham-operated animals acted as controls. Circulating
      and liver mRNA of IGF-I and its binding proteins (IGFBPs) were measured. RESULTS:
      LPS reduced IGF-I and IGFBP-3 by 20% in the cirrhosis group. LPS induced insulin
      resistance (HOMA) in both groups. CONCLUSION: Our results show that LPS
      administered to cirrhotic rats induced changes in the IGF system that facilitate
      catabolism. This may be of importance for the accelerated tissue loss during
      infection and the acute phase response in liver cirrhosis.

PMID- 19180988
TI  - The frequency of gastric amyloidosis in baboons. A 22-year survey at a large
      primate facility.
AB  - BACKGROUND: Systemic amyloidosis, caused by abnormal tissue accretion of plasma
      proteins, affects several organs of the gastrointestinal (GI) tract. Gastric
      amyloidosis, rare in humans, has only been reported once in animals. MATERIALS
      AND METHODS: Gastric amyloidosis was sought for in baboons with systemic
      amyloidosis. RESULTS: During the past 22 years (between January 1986 and January
      2007) a mean of 3315 baboons/year (range 2578-3931) were housed at the Southwest
      National Primate Research Center. Gastric amyloidosis was found in 9 (10.2%) of
      the 88 baboons having a diagnosis of systemic amyloidosis. Consequently, the
      prevalence of gastric amyloidosis occurring since 1986 at this facility was 0.41
      baboons/year. Gastric amyloid deposits were found in the interstitial aspect of
      the lamina propria, replacing normal mucosal structures, in the submucosal stroma
      along the interface with the muscularis mucosae and in the interstitial tissue of
      submucosal lymphoid aggregates. In one of the animals, lumps of amyloid deposits
      with giant cells were found in the gastric mucosa. CONCLUSION: Baboons with
      systemic amyloidosis usually show increasing frequency of amyloid deposits in the
      liver, large intestine, lymph nodes, spleen and the small intestine. We now
      demonstrate that it may also involve the stomach. Why certain organs of the GI
      tract in baboons are more susceptible than others to be affected by the process
      of systemic amyloidosis remains unexplained. The apparent natural resistance of
      the stomach of baboons to be affected by systemic amyloidosis deserves further
      investigation. The review of the literature indicates that this is only the
      second report on gastric amyloidosis in baboons.

PMID- 19180989
TI  - Development and validation of a multi-dose neutropenic rat thigh infection model
      using real-time monitoring of Staphylococcus aureus growth in vivo.
AB  - BACKGROUND: Several animal models have been described using luminescent bacteria
      for non-invasive, real-time monitoring of infection in mice. In this study, a
      multidose rat thigh infection model with luminescent Staphylococcus aureus was
      developed for the evaluation of antibiotic efficacy. MATERIALS AND METHODS:
      Bioluminescent imaging and bacterial loads of S. aureus infected rat thighs with
      or without vancomycin treatment at different time-points post-infection were
      compared. RESULTS: Correlation between luminescence and bacterial load was
      observed based on the dose- and time-dependent activity of vancomycin in the
      model. CONCLUSION: While luminescence detection offered the advantage of
      monitoring an infection in live animals, limitations to this method included
      reduced sensitivity and a narrow dynamic range, as compared to a traditional
      tissue culturing method. Real-time luminescence monitoring of infection may be
      most appropriate for experiments where rapid in vivo assessment of compound
      efficacy is desired and absolute quantitation of colony forming units in infected
      tissue is not required.

PMID- 19180990
TI  - Nitric oxide effects on the function of aged cells ex vivo and in vivo.
AB  - BACKGROUND: Angiogenesis is impaired in most aged tissues. Accordingly, there is
      great interest in interventions that improve the ability of aged cells to undergo
      blood vessel formation and subsequent tissue repair. MATERIALS AND METHODS:
      Nitric oxide (NO), a mediator proposed to enhance angiogenesis, was administered
      (as the precursor SNAP, S-nitroso-N-acetylpenicillamine) to aortic ring explants
      from aged mice and to aged mice in two separate in vivo experiments: a PVA sponge
      implant model of angiogenesis and full thickness excisional dermal wounds.
      RESULTS: SNAP inhibited angiogenesis from the mouse aortic ring explants.
      However, there was a trend toward increased blood vessel formation in the sponges
      from the aged mice treated with SNAP. SNAP did not detectably enhance dermal
      wound healing or angiogenesis, but it significantly inhibited epidermal closure.
      CONCLUSION: These data underscore the complexity of using a single agent, even
      one with multiple mechanisms such as NO, to improve a clinical outcome such as
      angiogenesis or wound repair in aged animals.

PMID- 19180991
TI  - Further studies on long-term preservation of rat liver: Celsior versus UW
      solution.
AB  - The effects of Celsior solution were compared with those of the University of
      Wisconsin solution (UW) after 18 or 48 hours of cold storage in a perfused rat
      liver model. Lactate dehydrogenase (LDH), hyaluronic acid (HA) uptake,
      thiobarbituric acid-reactive substances (TBARS), tissue reduced (GSH) and
      oxidized glutathione (GSSG) and ATP were evaluated. Histochemical in situ
      evaluation ofLDH and reactive oxygen species (ROS) were also performed. No
      significant difference in LDH release, HA uptake, TBARS, ATP levels and GSH/GSSG
      ratio were observed between UW and Celsior solution when the livers were
      preserved for 18 hours. By contrast, when preservation was performed for 48
      hours, LDH release, TBARS and ROS formation were higher and the ATP levels,
      GSH/GSSG ratio and HA uptake were lower in the liver preserved by Celsior as
      compared with UW. Celsior solution was as effective as UW in liver preservation
      up to 18 hours but the superiority of UW over Celsior solution was obtained when
      liver was preserved for 48 hours.

PMID- 19180992
TI  - Modulation of eosinophil survival by epinastine hydrochloride, an H1 receptor
      antagonist, in vitro.
AB  - The influence of epinastine hydrochloride (EP) on eosinophil survival was
      examined by an in vitro cell culture technique. Nasal epithelial cells (NECs)
      were stimulated with 25 ng/ml TNF-alpha in the presence of EP (10 to 30 ng/ml).
      After 24 h, the culture supernatants were obtained and used as conditioned media
      of NECs (CM). Eosinophils (1 x 10(3) cells/ml) prepared from healthy human
      peripheral blood were incubated with 25% CM and eosinophil survival was assessed
      by trypan blue dye exclusion test 48 h later. CM prepared from NEC cultures pre
      treated with TNF-alpha and EP caused a decrease in eosinophil survival as
      compared with that from NEC cells pre-treated with TNF-alpha alone. The minimum
      concentration of EP that caused a significant decrease in eosinophil survival was
      25 ng/ml. The addition of EP into eosinophil cultures did not cause inhibition of
      eosinophil survival, which was prolonged by stimulation with granulocyte
      macrophage colony-stimulating factor (GM-CSF), even when 40 ng/ml EP was added to
      cell cultures. We then examined the levels of GM-CSF in CM by ELISA. Treatment of
      NECs with EP at more than 25 ng/ml, reduced the ability of NECs to produce GM-CSF
      in response to TNF-alpha stimulation. These results may suggest that EP
      suppresses eosinophil survival through the suppression of GM-CSF production from
      NECs induced by inflammatory stimulation and that this suppressive effect
      contributes, in part, to the therapeutic mode of action of EP on allergic
      diseases.

PMID- 19180993
TI  - Biodistribution and pharmacokinetics of transgenic pig-produced recombinant human
      factor IX (rhFIX) in rats.
AB  - BACKGROUND: Recombinant human factor IX (rhFIX) is a 56 kDa glycoprotein with
      full biological activity providing a guarantee of freedom from blood-borne viral
      contamination in the therapy of hemophilia B, but no data are available on the
      distribution of transgenic pig-produced rhFIX post injection (p.i.). Therefore,
      an 131I-radiolabeled rhFIX was developed to evaluate the distribution of rhFIX in
      rats. MATERIALS AND METHODS: rhFIX was labeled with the lodogen method. 131I
      rhFIX (25 microCi/25 microg/200 microl/rat) was intravenously injected through
      the tail vein in normal Sprague-Dawley (SD) rats and the biodistribution was
      examined from 5 min to 72 h p.i.. The pharmacokinetics were also evaluated from 5
      min to 96 h p.i. RESULTS: The radiolabeled efficiency and radiochemical purity of
      131I-rhFIX was over 96% and 98%, respectively. The biodistribution study showed
      that the rhFIX chiefly accumulated in the liver. The distribution and elimination
      half-life (t(1/2alpha) and t(1/2beta)) of 131I-rhFIX were 0.82 and 9.34 h,
      respectively. The maximum concentration in the plasma (Cmax) and the area under
      the concentration versus time curve (AUC(INF)) of 131I-rhFIX in rats were 3.09%
      injected dose (ID)/g and 15.3 h x % ID/g. CONCLUSION: The transgenic pig-produced
      rhFIX is mostly retained in the liver and the preclinical biodistribution and
      pharmacokinetic studies of 131I radiolabeled rhFIX are helpful for researching
      its biological effect in vivo.

PMID- 19180994
TI  - Effects of neonatal administration of diethylstilbestrol on aberrant crypt foci
      induced by 7,12-dimethylbenz[alpha] anthracene in rats.
AB  - Gastrointestinal carcinoma is affected environmental factors, however, it remains
      to be determined whether neonatal administration of an estrogenic endocrine
      disruptor, such as diethylstilbestrol (DES), affects gastrointestinal
      carcinogenesis. The effects of neonatally administered DES on gastrointestinal
      tumorigenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) were investigated
      in male and female rats. Male and female rats in group I were daily administered
      oil alone from 0-14 days after birth. Male and female rats in groups II and III
      were daily administered DES at 1 and 10 microg/rat, respectively. The
      administration periods of DES in subgroups a (IIa and IIIa), b (IIb and IIIb) and
      c (IIc and IIIc) were from 0-14, 0-5 and 6-14 days after birth, respectively. At
      28, 42 and 56 days after birth, all male rats were given 10 mg of DMBA. At 50
      days after birth, all female rats were given 10 mg of DMBA. In the digestive
      tracts of male rats, forestomach masses (FMs) in all groups (13-58%), small
      intestine masses in group IIIa (17%), and colon masses (CMs) in groups IIIa (8%)
      and IIIb (33%) were observed, although there were no significant changes in the
      incidence and number. In the digestive tracts of female rats, FMs in groups I
      (10%), IIa (13%), IIb (33%), IIc (25%) and IIIc (33%), CMs in groups IIa (6%) and
      IIIa (6%) were seen, although there were no significant changes in the incidence.
      Aberrant crypt foci (ACF) in the colon and rectum were seen in all male and
      female rats. The neonatal administration of DES in male rats increased the number
      of ACF while that in female rats did not. These results suggest that neonatal
      administration of DES may affect male colorectal carcinogenesis.

PMID- 19180995
TI  - The effect of chemotherapy against micrometastases and isolated tumor cells in
      lymph nodes: an in vivo study.
AB  - BACKGROUND: The effect of perioperative chemotherapy against micrometastasis has
      not been elucidated. An in vivo model was established in which a gastric cancer
      cell line, GCIY-EGFP, metastasizes spontaneously to the lymph nodes when
      inoculated subcutaneously. MATERIALS AND METHODS: After induction of the primary
      tumor by inoculation of 5 x 10(6) GCIY-EGFP cells into the lower abdominal wall
      of KSN nude mice, preoperative treatment with S-1 and docetaxel, or postoperative
      treatment with S-1 was given in addition to resection of the primary tumor to
      assess the efficacy of chemotherapy on isolated tumor cells (ITC) and
      micrometastases in the lymph nodes. RESULTS: Resection of the primary tumor led
      to spontaneous regression of ITC but not of micrometastases. Chemotherapy
      delivered at 3 weeks after the inoculation of tumor cells, whether before or
      after surgery, was effective against micrometastasis and reduced the risk of
      recurrence in the lymph nodes, although not as effective against the primary
      tumor. Once failed to be eradicated, nodal disease grew swiftly after cessation
      of the chemotherapy. CONCLUSION: ITC and micrometastases in the lymph nodes are
      vulnerable to chemotherapy. When objective response is achieved in a neoadjuvant
      setting, one may not need fear the risk of systemic disease spread during the
      course of the treatment.

PMID- 19180996
TI  - Aberrant activation of interleukin-9 receptor and downstream Stat3/5 in primary T
      cell lymphomas in vivo in susceptible B6 and resistant C3H mice.
AB  - BACKGROUND: Interleukin (IL)-2 family cytokine-mediated signal transduction plays
      important roles not only in normal development but also in the malignant
      transformation of lymphoid cells. However, little is known about the status of
      receptor activation and downstream signal transduction in primary lymphomas in
      vivo. MATERIALS AND METHODS: Primary T-cell lymphomas (TL) of mice were induced
      by X-ray irradiation. Expression and activation of IL-2 family cytokine receptors
      and downstream Janus kinase (Jak)-signal transducers and activators of
      transcription (Stat) pathway were determined. RESULTS: IL-9Ra was exceptionally
      highly expressed and phosphorylated in primary TL. IL-9Ralpha proteins in TL were
      heterogeneous due to different glycosylation. Downstream Stat3 and 5, but not
      Stat1, were also phosphorylated. There was a clear strain difference between
      susceptible C57BL/6 and resistant C3H mice in Stat3 and 5 activation and
      expression of Cyclin D1. CONCLUSION: Aberrant expression, modification and
      activation of IL-9Ralpha and Stat proteins contribute to in vivo growth of TL in
      a manner linking to the genetic susceptibility to TL induction.

PMID- 19180997
TI  - The frequency of histological features mimicking reflux esophagitis: a study in
      non-human primates.
AB  - BACKGROUND: The frequency of histological changes mimicking those described for
      reflux esophagitis in humans was assessed in a cohort of non-human primates
      (NHP). MATERIALS AND METHODS: A total of 121 consecutive esophagi (from 103
      baboons and 18 macaques) were classified according to Ismail-Beiji for reflux
      esophagitis in humans into grade 1, grade 2 and grade 3 esophagitis. RESULTS:
      Histological features compatible with reflux esophagitis were found in 28.2% of
      the baboons and in 22.2% of the macaques. Esophagitis grade 1 was more common in
      baboons (24%) than in macaques (6%), while esophagitis grade 2 was more common in
      macaques (17%) than in baboons (2%). CONCLUSION: Although the prevalence of
      reflux esophagitis in man is at least 2%, only a fraction of patients demonstrate
      histological features consistent with grades 1, 2 or 3 esophagitis. Hence, the
      finding that 27% of a cohort of consecutive, unselected NHP had grades 1, 2 or 3
      esophagitis at histology is remarkable. The possible causes for the difference
      between species, such as the oblique position often adopted by NHP during the
      gastric phase of digestion, the diet, regurgitation and subsequent re-ingestion,
      as well as the stress of NHP when kept in captivity, are reviewed.

PMID- 19180998
TI  - The prevalence of colonic amyloidosis in baboons. A 22-year survey at a large
      primate facility.
AB  - BACKGROUND: Colonic amyloidosis has been previously reported in animals, however
      its prevalence rate has not yet been explored. The aim of the present work was to
      assess the prevalence of colonic amyloidosis at the Southwest National Primate
      Research Center since 1986. MATERIALS AND METHODS: Colonic amyloidosis was sought
      in autopsy material from baboons collected under the diagnosis of systemic
      amyloidosis. RESULTS: Between 1986 and 2007, a mean of 3315 baboons per year
      (range 2578-3931) were housed at the Southwest National Primate Research Center.
      After examination, colonic amyloidosis was detected in 6 (6.8%) of the 88 baboons
      with systemic amyloidosis, yielding a prevalence rate of 0.27 cases per year
      since 1986. Colonic amyloid deposits were found in the interstitial aspect of the
      lamina propria, often replacing normal mucosal crypts of Lieberkuhn. CONCLUSION:
      It was observed that only 6.8% of animals with systemic amyloidosis examined
      between 1986 and 2007 developed colonic amyloidosis. The apparent natural
      resistance to colonic amyloidosis in baboons presenting systemic amyloidosis
      deserves to be further investigated.

PMID- 19180999
TI  - Effects of luteolin on distribution and metabolism of 2-aminofluorene in male
      Sprague-Dawley rats.
AB  - The effects of oral luteolin on the N-acetylation and metabolism of 2
      aminofluorene (AF) in vivo were investigated in bladder, blood, colon, kidney,
      liver, feces, urine, cerebrum, cerebellum and pineal gland from male Sprague
      Dawley rats. Major metabolites such as AAF, 1-OH-AAF, 3-OH-AAF, 8-OH-AAF and 9-OH
      AAF were found in bladder tissues; AAF, 1-OH-AAF, 5-OH-AAF and 8-OH-AAF were
      found in blood samples; AAF, 1-OH-AAF, 3-OH-AAF, 5-OH-AAF, 8-OH-AAF and 9-OH-AAF
      were found in colon tissues; AAF, 1-OH-AAF, 3-OH-AAF and 9-OH-AAF were found in
      kidney tissues; AAF, 1-OH-AAF, 3-OH-AAF and 8-OH-AAF were found in liver tissues,
      AAF, 1-OH-AAF, 3-OH-AAF, 5-OH-AAF, 7-OH-AAF, 8-OH-AA and 9-OH-AAF were found in
      feces and urine samples; AAF, 1-OH-AAF, 3-OH-AAF and 8-OH-AAF were found in
      cerebrum tissues; AAF, 1-OH-AAF, 3-OH-AAF and 7-OH-AAF were found in cerebellum
      tissues; but only AF and AAF were found in pineal gland in rats treated with AF
      (50 mg/kg) for 24 h. Pretreatment of rats with luteolin (30 mg/kg) 24 h prior to
      the administration of AF (50 mg/kg) and luteolin given with AF concomitantly led
      to a decrease in the amounts of 3-OH-AAF and 9-OH-AAF and an increase in the
      amounts of 1-OH-AAF and 8-OH-AAF in bladder tissues. In blood samples, there were
      significant decreases of AAF, 1-OH-AAF and 8-OH-AAF after rats were treated with
      luteolin for 24 h prior to AF but luteolin with AF at the same time caused an
      increase in 1-OH-AAF. In colon tissues, there were significant decreases of AF, 1
      OH-AAF, 3-OH-AAF, 5-OH-AAF and 9-OH-AAF after rats were treated with luteolin for
      24 h then AF but the amounts of AF, 1-OH-AAF, 5-OH-AAF and 9-OH-AAF decreased and
      AAF and 8-OH-AAF increased in rats treated with luteolin and AF at the same time.
      In kidney tissues, there were significant decreases of AF, AAF and 3-OH-AAF after
      rats were treated with both compounds at the same time, but luteolin for 24 h
      then AF treatment led to significant decreases of 3-OH-AAF. In liver samples,
      after rats were treated with luteolin and AF at the same time, the amounts of AAF
      and 1-OH-AAF significantly decreased but 8-OH-AAF increased. However, rats
      treated with luteolin for 24 h then with AF led to significant decreases of AAF,
      1-OH-AAF and 3-OH-AAF. In feces samples, there were significant increases of AAF,
      3-OH-AAF, 7-OH-AAF, 8-OH-AAF and 9-OH-AAF after rats were treated with both
      compounds at the same time but luteolin for 24 h then AF treatment led to a
      significant increase of AF, 1-OH-AAF and 8-OH-AAF and a decrease AAF and 3-OH
      AAF. In urine samples, there were significant increases of AF, AAF, 1-OH-AAF, 3
      OH-AAF, 5-OH-AAF and 9-OH-AAF but a decrease of 8-OH-AAF after rats were treated
      with both compounds at the same time. However, the luteolin for 24 h then AF
      treatment led to significant increases of AF, AAF and 1-OH-AAF but decreases of 3
      OH-AAF and 5-OH-AAF. In cerebrum samples, there were significant increases ofAF
      but decreases of 1-OH-AAF and 8-OH-AAF after rats were treated with both
      compounds at the same time; luteolin for 24 h then AF treatment of rats led to
      significant increase of 1-OH-AAF and decreases AF, AAF and 8-OH-AAF. In
      cerebellum samples, there were significant increases of AAF and decreases of 1-OH
      AAF and 3-OH-AAF after rats were treated with both compounds at the same time,
      there is a significant increase of AAF but decrease of 1-OH-AAF, 3-OH-AAF and 7
      OH-AAF after the luteolin treated for 24 h then AF were treated to the rats. In
      pineal gland samples, there were significant increases ofAAF after rats were
      treated with both compounds at the same time. However, luteolin treated for 24 h
      then AF were treated to the rats which increase AAF but decrease AF.

PMID- 19181000
TI  - The role of urokinase-type plasminogen activator (uPA) and transforming growth
      factor beta 1 (TGFbeta1) in muscle regeneration.
AB  - Skeletal muscle regeneration is a highly synchronized process involving the
      activation of various cellular and molecular events, coordinating inflammation
      and regeneration processes which are crucial for the beneficial outcome of tissue
      remodeling. Fibrosis, a failure of tissue remodeling, is initiated with muscle
      regeneration; however, it is the result of an excessive inflammatory response,
      representing an imbalance between enhanced production and deposition and impaired
      degradation of extracellular matrix (ECM) components of the muscle. Therefore,
      factors influencing the relative degree of muscle fiber regeneration as compared
      to the amount of scar formation have a critical role in functional muscle
      remodeling. Herein we have focused on the role of urokinase-type plasminogen
      activator (uPA) and transforming growth factor beta 1 (TGF/1) in ECM degradation
      and reconstitution in muscles.

PMID- 19181001
TI  - Electrochemotherapy-induced radiation recall in a cat.
AB  - Electrochemotherapy is gaining popularity for the treatment of malignancies of
      companion animals due to its efficacy and low cost. In this paper, we describe
      the successful treatment of a recurring fibrosarcoma in a cat by using cisplatin
      selectively driven within the tumor cells by trains of biphasic pulses. The cat's
      tumor did not recur over the following five months, however the cat did
      experience severe erythema at the site of previous irradiation, followed by moist
      desquamation and ulcer that required debridement and prolonged therapy with
      steroids and antihistaminic drugs. The symptoms and the response to symptomatic
      therapy were strongly suggestive of radiation recall. Electrochemotherapy (ECT)
      should be used with caution in previously irradiated areas. Further studies are
      warranted in this field due to its potential as a rescue for relapsing tumors.

PMID- 19181002
TI  - Prostate as sole unusual recurrence site of lymphoma in a dog.
AB  - A ten-year-old intact male Rottweiler dog was examined for sudden onset of
      stranguria and pollakiuria. The dog had an intestinal lymphoma treated three
      years before with chemotherapy. Ultrasonographic examination of the abdomen
      showed a large dyshomogeneous prostate with an over-distended bladder.
      Cytological examination of the fine-needle aspirate from the prostate yielded a
      diagnosis of lymphoma. The diagnosis was confirmed by histopathological
      examination. The dog was treated with multi-drug chemotherapy and achieved a
      complete remission. The dog remained in complete remission for one year from the
      re-institution of chemotherapy before dying of recurrence. Lymphoma rarely
      invades the prostate in the dog. To the best of our knowledge this is the first
      report of prostatic recurrence of lymphoma in a canine patient originally
      affected by intestinal lymphoma and treated with chemotherapy.

PMID- 19181003
TI  - Adjuvant carboplatin for the treatment of intestinal carcinoid in a dog.
AB  - A ten-year-old castrated male dog was presented due to a two-day history of
      constipation and tenesmus. At physical examination, the dog was depressed and
      unresponsive. Aggressive behavior was elicited by deep abdominal palpation and a
      mass was detected during the examination. Imaging studies evidenced a large
      jejunal mass. The lesion (6 cm in diameter) was surgically removed. The
      histopathology report gave a diagnosis of completely excised intestinal
      carcinoid. The patient recovered well from the procedure and was scheduled for
      adjuvant chemotherapy. The dog received four doses of carboplatin (300 mg/m2)
      every three weeks without showing signs of toxicity. The dog is still in
      remission after 18 months and is reassessed on a three-month schedule. This
      report represents the first description of long-term control of intestinal
      carcinoid in the dog and the first of adjuvant chemotherapy for this rare and
      aggressive neoplasm.

PMID- 19181004
TI  - Antibacterial effect of octylcyanoacrylate against methicillin-resistant
      Staphylococcus aureus isolates from patients with chronic suppurative otitis
      media.
AB  - There has been a steady increase in the number of cases of methicillin-resistant
      Staphylococcus aureus (MRSA) otorrhea; this is a growing medical concern. For
      otological surgery in children, octylcyanoacrylate can be an alternative method
      of closure for surgical incisions. Recent in vitro studies have shown that
      octylcyanoacrylate is effective as an antimicrobical barrier. To date, there have
      been only rare reports on the antibacterial effect of octylcyanoacrylate against
      MRSA. The purpose of this study is to determine the antimicrobial effects of
      octylcyanoacrylate against the MRSA that was isolated from patients with chronic
      suppurative otitis media. MATERIALS AND METHODS: Clinical MRSA (n=20) bacteria
      and methicillin-sensitive SA (MSSA) (n=20) were obtained from patients. The
      susceptibilities to various antibiotics were determined by disk diffusion method.
      RESULTS: MSSA was sensitive to octylcyanoacrylate. The antibacterial activity of
      octylcyanoacrylate was weak against MRSA. CONCLUSION: Our results demonstrated
      that octylcyanoacrylate has slight antibacterial activity against MRSA.

PMID- 19181005
TI  - In vivo models for heart failure research.
AB  - The medical treatment of heart failure (HF) is associated with 50% survival at 5
      years, thus being one of the major causes of mortality in Western countries. An
      understanding of the pathophysiology of HF is essential for the development of
      novel efficient therapies. Consequently, the use of animal models is
      indispensable. In addition, the development of new in vivo models of HF is
      critical for the evaluation of treatments such as gene therapy, mechanical
      devices and new surgical approaches. However, every animal model has advantages
      and limitations and none of them is suitable to study all aspects of HF. Besides
      the technical determinants of a model, species, strain and gender affect the
      pathophysiology of a given heart pathogenesis and, therefore, have to be
      considered in each animal model. The most common in vivo models used in
      cardiology research and in particular in HF remodeling are presented.

PMID- 19181006
TI  - Effects of curcumin on N-bis(2-hydroxypropyl) nitrosamine (DHPN)-induced lung and
      liver tumorigenesis in BALB/c mice in vivo.
AB  - Curcumin (diferuloylmethane), a phenolic compound from the plant Curcuma longa
      (Linn.) has been shown to exhibit antitumor activity and apoptosis in many human
      cancer cell lines including that of lung and liver cancer. In this study,
      curcumin was evaluated in BALB/c mice for its ability to inhibit pulmonary and
      liver adenoma formation and growth after they were orally treated with N-bis(2
      hydroxypropyl)nitrosamine (DHPN). Animals were treated with DHPN in water for
      approximately 14 days before multiple doses of curcumin were given
      intraperitoneally. It was found that 200 microM curcumin reduced lung and liver
      tumor multiplicity by 37% (p<0.05) and 30% (p<0.05) respectively. The results
      indicated that curcumin significantly inhibited pulmonary and liver adenoma
      formation and growth in BALB/c mice. The precise mechanism by which curcumin
      inhibits lung and liver tumorigenesis remains to be elucidated. Thus, curcumin
      appears to be a promising new chemotherapeutic and preventive agent for lung and
      liver cancer induced by DHPN.

PMID- 19181007
TI  - Inhibition of human cytomegalovirus IE gene expression by dihydro-beta-agarofuran
      sesquiterpenes isolated from Euonymus species.
AB  - The development of strategies intended to inhibit human cytomegalovirus (HCMV)
      immediate-early (IE) antigen expression is an important goal in research designed
      to prevent and treat certain forms of cancer. The aim of this study was to
      identify potent IE antigen-targeting natural compounds as antitumor promoters in
      an in vitro model of tumor promotion. Nineteen dihydro-beta-agarofuran
      sesquiterpenes isolated from Euonymus species were evaluated for their ability to
      inhibit HCMV IE antigen expression in human lung adenocarcinoma (A549) cells.
      Five esters of penta- and hexahydroxydihydro-beta-agarofuran proved to be active
      components in these Euonymus species, inhibiting the IE antigen expression of
      HCMV. The highest activity was displayed by 2beta,6alpha,15-triacetoxy1beta
      benzoyloxy-9alpha-nicotinoyloxydihydro-beta-agarofuran. These effective compounds
      may be regarded as prototypes of antitumor promoters, as secondary
      chemopreventive agents which can modify or halt tumor promotion in general.

PMID- 19181008
TI  - Early modification of c-myc, Ha-ras and p53 expressions by N-methyl-N
      nitrosourea.
AB  - Methylnitrosourea (MNU) is a well-known pluripotent direct-acting carcinogen.
      Formation of MNU following incubation of various meats with additional nitrite
      under in vitro acidic conditions is possible. It is possible that many species,
      including humans, are exposed to carcinogenic MNU, generated in their alimentary
      tract. Previously, an animal model was developed by our research group to
      investigate the expression of three genes c-myc, Ha-ras and p53 as early
      molecular epidemiological biomarkers of carcinogenic exposure or carcinogenesis
      caused by DMBA (dimethylbenz[alpha]anthracene). The aim of this study was to
      investigate the early effect of MNU on the gene expression levels. MNU is a
      direct-acting carcinogen which spontaneously and rapidly degrades, so any effect
      on the gene expression is observed in 24 hours. Our results show the maximum
      effect in vivo on the gene expression at 12 hours after the MNU treatment; on the
      other hand, 24 hours after the treatment, the elevated gene expressions decreased
      in target organs (bone marrow, lung, lymph nodes). Our results correspond to
      "long-term" experiments of the carcinogenic effect of MNU in different target
      organs. Our findings suggest that MNU has an impact on the expression of c-myc,
      Ha-ras and p53 genes in 12 hours, especially in bone marrow. Overexpression of
      these genes occurs as an early biological effect of exposure to chemical
      carcinogens. According to our results, the high expression of these genes could
      indicate MNU exposure and these genes could take part in MNU-induced
      tumorigenesis.

PMID- 19181009
TI  - Validation of the energy index point score to serially measure the degree of
      disability in patients with chronic fatigue syndrome.
AB  - BACKGROUND: A simple quantitative accurate method for assessing the degree of
      fatigue in patients with chronic fatigue syndrome (CFS) is necessary for
      physicians and patients. Severity of the disease and recovery can, thus, be
      assayed. PATIENT AND METHODS: From February 1-27, 2007, fifty-six consecutive CFS
      patients at a single treatment center were simultaneously evaluated by the
      patient with the fatigue severity score (FSS), and by consensus of both patient
      and physician by the energy index (EI) point score. RESULTS: The FSS and EI
      correlated well, 0.67, p<0.001. CONCLUSION: The El point score is a validated
      reliable method to assess fatigue in CFS patients.

PMID- 19181010
TI  - Salvage surgery for locoregional failure after definitive radiotherapy for base
      of tongue cancer.
AB  - In this study, the results of definitive radiotherapy (RT) and salvage surgery
      treatment of base of tongue cancer were evaluated. A total of 94 consecutive
      patients (16 female and 78 male) with T1-4, NO-3 and MO disease underwent
      definitive RT between 1992 and 2005. External beam RT alone (mean dose, 63 Gy) or
      external beam RT (mean dose 61 Gy) with brachytherapy boost (mean dose, 17 Gy)
      was given for 50 and 44 patients, respectively. Eight patients were subjected to
      neck node dissection, generally at the time of brachytherapy. At a median follow
      up time of 95 months, 37 (39%) patients had no residual disease or locoregional
      recurrence, 34 (36%) patients had locoregional residual disease and 23 (25%)
      patients developed locoregional recurrence. The 5-year cause-specific survival
      for all patients was 45% (43 of 94). In multivariate analysis, N2-3 stage and
      histological grade 3 proved to be independent negative predictors of cause
      specific survival (relative risk: 22 and 3.1, respectively). The overall number
      of patients with locoregional failure was 57. Salvage surgery was possible in 18
      (32%) patients; more than half of the patients (31 of 57) with locoregional
      failure were not suitable for salvage surgery due to unresectable disease, poor
      health status or distant metastasis. Salvage surgery was successful in 10 (56%)
      patients, while 8 patients developed a second locoregional recurrence. For
      patients undergoing definitive RT, more effective follow-up and care is needed to
      increase the rate of salvage surgery.

PMID- 19181011
TI  - Late liver metastases of choroidal melanoma detected by laparoscopy.
AB  - Choroidal melanoma represents the primary intraocular malignancy in adults with a
      reported incidence of about 4000 cases per year. The liver is the sole site of
      metastases in more than 80% of cases and is affected in up to 90% of patients who
      develop metastatic disease. Patients with metastatic melanoma have usually a
      median survival of 6 months. In the present paper, the case of a 42-year-old
      woman with choroidal melanoma who underwent surgery and was followed up for 7
      years with no evidence of relapse is reported. Eight months later she had a car
      accident and was admitted to the hospital complaining of abdominal pain, lack of
      appetite and asthenia. At physical examination, jaundice and hepatomegaly were
      found. Abdominal ultrasonography revealed the presence of several hypoechoic
      lesions, and liver function was compromised due to coagulation deficiency. Thus,
      the diagnosis of metastatic choroidal melanoma was obtained by video-assisted
      laparoscopy that showed disseminated darkly pigmented lesions on the surface of
      the liver. The patient died of liver failure three months later. At autopsy,
      histopathological examination of the liver confirmed the diagnosis, excluding
      local recurrence of the choroidal melanoma.

PMID- 19181012
TI  - Umbilical endometriosis, our experience.
AB  - BACKGROUND: Endometriosis is the presence of functioning endometrial tissue
      outside the uterine cavity. Umbilical endometriosis has been reported in more
      than one hundred cases and the umbilicus represents the location of 0.5-1% of
      ectopical endometrioses. A correct differential diagnosis can be difficult and
      the use of epiluminescence and MRI is suggested for the accuracy of preoperative
      diagnosis. PATIENTS AND METHODS: We report our experience in preoperative
      differential diagnosis and treatment of four cases of umbilical endometriosis. An
      accurate anamnesis and clinical examination together with the use of 13 MHz probe
      ultrasonography with echocolor duplex scan led us to an accurate pre-operative
      diagnosis of umbilical endometriosis. The surgical approach to umbilical
      endometriosis represented an important step in achieving a satisfying result.
      RESULTS AND CONCLUSION: In all treated cases, a hemi-circumferential incision in
      the inner aspect of the umbilical opening was performed allowing adequate access
      to the lesion and umbilical repositioning. At the follow-up visit (from 6 to 24
      months after surgery), no symptoms or signs of recurrence were evidenced. A
      natural-looking umbilicus was observed in all cases with minimal visible scars.

PMID- 19181013
TI  - Inflammatory pseudotumor of the hypopharynx: clinical diagnosis,
      immunohistochemical findings and treatment of this rare disease.
AB  - Inflammatory pseudotumor (IPT) is a rare benign lesion, often imitating a
      malignant disease. An IPT was found in the sinus piriformis of a 40-year-old male
      who suffered from dysphagia, globus feeling and a weight loss of 5 kilograms in
      six months. Neither common infections previously described in combination with
      IPT such as human herpes virus (HHV) 8, human immunodeficiency virus (HIV) or
      acute Epstein Barr virus (EBV), nor evidence of manifestation of a systemic
      mastocytosis or a malignant disease were found. The primary therapy for IPT in
      locations other than the orbita is complete resection, if this is not applicable
      or recurrence occurs then cyclosporine, chlorambucil, indometacin or radiation
      have been used as alternative treatments. A transoral laser-assisted resection
      was performed in the case described here, resulting in a complete and lasting
      cure.

PMID- 19181014
TI  - Recurrent atypical eccrine spiradenoma of the forehead.
AB  - Eccrine spiradenoma is an uncommon but well recognized benign adnexal tumour of
      the eccrine sweat glands. It can appear at any age, but the highest rate of
      incidence is observed among young adults, without any sex predilection. The
      commonest clinical presentation is a solitary blue-red dermal or subcutaneous
      cystic nodule, ranging from 0.3 to 5 cm in diameter. Malignant transformation is
      a rare phenomenon, presenting as a rapidly enlarging nodule within a long
      standing lesion. We report a case of eccrine spiradenoma in a thirty-six-year-old
      man who presented with a recurrent soft-tissue neoplasm of the forehead, with
      cytological atypia. The differential diagnosis of this tumour, as well as its
      possible malignant transformation, is discussed.

PMID- 19181015
TI  - Systemic sclerosis associated with rectal cancer. Case report and a brief review
      of the literature.
AB  - Autoimmune diseases may appear as paraneoplastic syndromes during the course of a
      neoplastic disease, the most common being dermatomyositis/ polymyositis. The
      association of systemic sclerosis and cancer is not clear. The case of a 56-year
      old male with rectal cancer and systemic sclerosis where the coexistence of the
      two diseases was closely related, so that scleroderma was considered a
      paraneoplastic syndrome rather than a concomitant morbid condition, is presented.

PMID- 19181016
TI  - Low-dose oral metronomic chemotherapy prevents mobilization of endothelial
      progenitor cells into the blood of cancer patients.
AB  - Circulating endothelial progenitor cells (EPCs) actively supply cells that may
      participate in tumor angiogenesis. The differing effects of low-dose metronomic
      trofosfamide as opposed to conventional dose-dense chemotherapy on plasma levels
      of vascular endothelial growth factor (VEGF) and the numbers of circulating EPC
      are reported. PATIENTS AND METHODS: Blood samples were obtained from cancer
      patients, 18 receiving oral metronomic chemotherapy of trofosfamide with or
      without celecoxib, and 24 receiving conventional dose-dense chemotherapy, eight
      of them in adjuvant intention. Mononuclear cells were analyzed by flow cytometry
      for CD34, CD45 and vascular endothelial growth factor-receptor 2 (VEGF-R2)
      coexpression, defining EPCs, and for plasma levels of VEGF by ELISA at day 0, 10
      and 21 of therapy. RESULTS: After conventional dose-dense chemotherapy, the
      numbers of circulating EPCs and the VEGF plasma concentrations increased sharply,
      doubling pretherapeutic levels at day 21. In contrast, under low-dose metronomic
      chemotherapy, the numbers of circulating EPCs decreased significantly and VEGF
      plasma concentrations remained unchanged. CONCLUSION: These observations provide
      evidence that conventional dose-dense chemotherapy leads to rebound EPC
      mobilization even when given with adjuvant intention, while low-dose metronomic
      scheduling of cytotoxic substances such as trofosfamide may sharply reduce EPC
      release into the circulation.

PMID- 19181017
TI  - DNA aneuploidy study for early detection of chromosomal abnormality in patients
      with aplastic anemia: prognostic and therapeutic implications.
AB  - BACKGROUND: Undetected aneuploidy exists in a large percentage of patients with
      aplastic anemia at the time of diagnosis, which may not be identified by
      conventional cytogenetics. The presence of aneuploidy at any time in the clinical
      course implies poor prognosis in such patients. This warrants a need for the
      early detection of chromosomal abnormalities for prognosis and delineation of
      therapeutic modalities. PATIENTS AND METHODS: Fifty patients with aplastic anemia
      and 30 controls were studied with an aim to determine the role of aneuploidy as
      an indicator of chromosomal abnormalities. DNA aneuploidy analysis was carried
      out by flow cytometry using Mod Fit-LT V3.0 software, whereas chromosomal
      analysis was performed by conventional cytogenetics. RESULTS: DNA aneuploidy was
      present in 14% of cases and chromosomal abnormalities were found in 4% of cases
      of aplastic anemia at the time of diagnosis before therapy. Overall, DNA
      aneuploidy was detected in 36% of cases by flow cytometry, whereas the
      cytogenetic method revealed chromosomal abnormalities in 14% of cases of aplastic
      anemia. Flow cytometric analysis showed hypodiploidy in one patient at the time
      of diagnosis who developed monosomy 7 during follow-up. All patients with
      hypodiploidy had short survival and they did not respond to therapy. CONCLUSION:
      The present study demonstrates the role of flow cytometry in the early detection
      of chromosomal abnormalities in patients at a time when they remain undetected by
      conventional cytogenetics. The presence of DNA aneuploidy in patients with
      aplastic anemia may be an early indicator of subsequent overt cytogenetic
      abnormality, associated with poor response to immunosuppressive therapy and a
      lower survival.

PMID- 19181019
TI  - Reconciling technology and humanity in health care.

PMID- 19181018
TI  - A study of surgical psychoncology in breast cancer: perioperative variation of
      prolactin serum levels in women with operable breast cancer in relation to their
      maternal psychological behaviour.
AB  - BACKGROUND: The pituitary hormone prolactin (PRL) may be a potential growth
      factor for breast cancer. High blood levels of PRL are associated with a poor
      prognosis in metastatic breast cancer whereas hyperprolactinemia after breast
      surgery may predict a better prognosis in women with operable breast cancer. The
      lack of postoperative hyperprolactinemia would represent the consequence of an
      alteration in the neuroendocrine control of breast cell proliferation. On this
      basis, a study was planned to establish the relation which exists between changes
      in PRL perioperative secretion and the psychological maternal behaviour in women
      with operable breast cancer. PATIENTS AND METHODS: The study included 20 patients
      with operable breast cancer. Serum levels of PRL were measured before and 7 days
      after breast surgery. The maternal behaviour was investigated by the Rorschach
      test. RESULTS: Surgery-induced hyperprolactinemia occurred in 7/20 patients. The
      Rorschach test documented an absence of a maternal profile in 13/20 patients. The
      proportion of surgery-induced hyperprolactinemia was significantly higher in
      patients presenting a normal maternal profile than in those who lacked a maternal
      behaviour. CONCLUSION: The results, by showing a higher proportion of
      postoperative hyperprolactinemia in women with breast cancer who maintained a
      maternal behaviour, would suggest that the poor prognosis associated with the
      absence of surgery-induced hyperprolactinemia in patients with operable breast
      cancer may, at least in part, be the consequence of a suppression of maternal
      psychological behaviour.

PMID- 19181020
TI  - The Austrian health care system.

PMID- 19181021
TI  - Impact of the rural health development programme in the Islamic Republic of Iran
      on rural-urban disparities in health indicators.
AB  - By 1979, 50 years of uneven development and modernization by governments prior to
      the Islamic Revolution had left rural parts of the Islamic Republic of Iran with
      extremely low economic and health status. This paper reports on the impact of the
      rural health development programme implemented as an effective and inexpensive
      way to improve the heath of the rural population, especially mothers and
      children. It describes the system of rural health centres, health houses and
      community health workers (behvarz) and demonstrates the effectiveness of the
      programme through declining measures of rural-urban disparities in health
      indicators. The implications of inexpensive rural health policies for other
      countries in the region such as Afghanistan and central Asian countries with a
      similar sociocultural structure are discussed.

PMID- 19181022
TI  - Improving quality and reducing inequities: a challenge in achieving best care.
AB  - The health care quality chasm is better described as a gulf for certain segments
      of the population, such as racial and ethnic minority groups, given the gap
      between actual care received and ideal or best care quality. The landmark
      Institute of Medicine report Crossing the Quality Chasm: A New Health System for
      the 21st Century challenges all health care organizations to pursue six major
      aims of health care improvement: safety, timeliness, effectiveness, efficiency,
      equity, and patient-centeredness. "Equity" aims to ensure that quality care is
      available to all and that the quality of care provided does not differ by race,
      ethnicity, or other personal characteristics unrelated to a patient's reason for
      seeking care. Baylor Health Care System is in the unique position of being able
      to examine the current state of equity in a typical health care delivery system
      and to lead the way in health equity research. Its organizational vision,
      "culture of quality," and involved leadership bode well for achieving equitable
      best care. However, inequities in access, use, and outcomes of health care must
      be scrutinized; the moral, ethical, and economic issues they raise and the
      critical injustice they create must be remedied if this goal is to be achieved.
      Eliminating any observed inequities in health care must be synergistically
      integrated with quality improvement. Quality performance indicators currently
      collected and evaluated indicate that Baylor Health Care System often performs
      better than the national average. However, there are significant variations in
      care by age, gender, race/ethnicity, and socioeconomic status that indicate the
      many remaining challenges in achieving "best care" for all.

PMID- 19181023
TI  - The "salutogenic" approach--designing a health-promoting hospital environment.
AB  - Hospitals are supposed to be places of healing and recovery, where the unwell go
      to get well again. But in many cases the healing environment is anything but-
      "wellness" has given way to functionality, potentially hampering not only the
      recovery of patients but also the productivity and efficiency of the hospital
      itself. Most health care facilities have been designed around the treatment of
      disease--with rooms full of the latest equipment; they appear to be state-of-the
      art, treatment at its finest. But what we really need to ask is; is it a healthy
      building?

PMID- 19181024
TI  - Virtual patient simulation for prevention of medical error: beyond just technical
      upskilling.
AB  - Virtual patient simulation is a well established mode of medical education for
      many technically oriented clinical skills. Resuscitation Annie has been used for
      teaching cardiopulmonary resuscitation for many years and other similar
      simulation has been used extensively for teaching colonoscopy, delivering babies,
      suturing, and a variety of surgical techniques and procedures. There are very few
      medical schools that would not routinely use such simulation as a standard part
      of their curriculum. This is not because they are cost effective (although they
      are) but rather because they have been shown to reduce human error in performing
      these clinical skills and provide a safe environment for doctors to learn such
      procedures without endangering real patients. Simulation has taken many forms in
      Medicine including: (1) Computer-based simulations; (2) Standardised patients
      widely used in OSCE training and examination; (3) Virtual environments; (4)
      mannequins such as Resuscitation Annie, and (5) so-called "high fidelity"
      simulations resembling as much as possible the actual clinical situations. These
      forms of simulation have been used to teach the important skill of clinical
      decision-making as well as technical procedures (Owen, 2008).

PMID- 19181025
TI  - Emerging nutrition challenges: policies to tackle under-nutrition, obesity and
      chronic diseases.
AB  - On 19 May, 2008, Mexico's Secretary of Health, Dr Jose Angel Cordova Villalobos,
      hosted an event entitled Emerging Nutrition Challenges: Policies to Tackle Under
      nutrition, Obesity and Chronic Diseases. Held in conjunction with the World
      Health Assembly (WHA) in Geneva, nearly 100 delegates from over 30 countries
      attended. The International Association of Infant Food Manufacturers and the
      International Hospital Federation supported Mexico in its sponsorship of this
      event. Dr Villalobos provided opening remarks including an overview of Mexico's
      public policies to prevent obesity and chronic diseases. Dr. Mauricio Hernandez,
      Mexico's Undersecretary of Health, moderated as six experts from around the world
      spoke on issues relating to the nutrition "double burden" (i.e. malnourishment
      and obesity), successful interventions and policy opportunities for improving
      nutrition, preventing obesity and enhancing health outcomes. Following are
      abstracts from their presentations.

PMID- 19181026
TI  - The D-bate rages.

PMID- 19181027
TI  - What is your diagnosis? Bullous Sweet's syndrome with neutrophilic alveolitis.

PMID- 19181028
TI  - What's eating you? Cutaneous myiasis (Wohlfahrtia magnifica).

PMID- 19181029
TI  - Varicella pneumonia with immune thrombocytopenic purpura: a patient with multiple
      complications.
AB  - Viral syndromes can present with various cutaneous manifestations, from the
      morbilliform eruption of measles to the papular lesions of molluscum. The
      systemic manifestations of viral illness can be similarly varied, with different
      presentations in each individual. We describe a patient with recently diagnosed
      AIDS who presented to the emergency department with hemorrhagic papules and
      shortness of breath. She was found to be severely thrombocytopenic, and a Tzanck
      smear revealed multinucleate giant cells. She received a diagnosis of immune
      thrombocytopenic purpura (ITP) and primary varicella pneumonia. Acyclovir and
      intravenous immunoglobulin (IVIG) were initiated. Her respiratory status improved
      after 5 days of treatment and her cutaneous lesions healed, with some scarring.
      We believe the rapid resolution and benign outcome of this patient's varicella
      infection may have been attributed to the concomitant initiation of IVIG with
      antiviral therapy.

PMID- 19181030
TI  - Amyopathic necrotizing dermatomyositis secondary to an underlying malignancy: a
      case report and review of the literature.
AB  - We describe a patient with amyopathic dermatomyositis (DM) secondary to an
      unusual malignancy. Although the association between amyopathic DM and malignancy
      has been established, our case report is unique in that the patient exhibited
      necrotic lesions on her skin. Furthermore, histopathologic examination of the
      skin lesions demonstrated a combination of epidermal findings typical of DM in
      addition to a necrotizing, paucicellular vasculopathy. The first indication of an
      underlying malignancy in this patient was the clinical findings of DM. Prompt
      identification of such findings may assist in the diagnosis and treatment of the
      associated malignancy.

PMID- 19181032
TI  - Dermatology Foundation career development award recipients and retention in full
      time academic dermatology.

PMID- 19181031
TI  - Antibiotic-resistant Propionibacterium acnes suppressed by a benzoyl peroxide
      cleanser 6%.
AB  - Adding topical benzoyl peroxide (BPO) to antibiotics can reduce resistant
      Propionibacterium acnes in patients with acne receiving antibiotic therapy.
      Benzoyl peroxide often is formulated as a wash, but no published data exist
      regarding BPO wash formulation efficacy in reducing resistant strains of P acnes.
      This 3-week, open-label, single-center study evaluated the effects of BPO
      cleanser 6% on antibiotic-resistant P acnes populations. The study involved 30
      healthy adults who were free of acne but had high facial P acnes populations
      (10,000 colonies/cm2 or more) resistant to erythromycin and tetracycline at 8
      microg/mL or more and 2 microg/mL or more, respectively. Participants applied BPO
      cleanser 6% once daily. Quantitative P acnes cultures were obtained at baseline
      and weekly for 3 weeks. At baseline, resistance to erythromycin, tetracycline,
      doxycycline, minocycline, and clindamycin was present in 100% (30/30), 97%
      (29/30), 83% (25/30), 63% (19/30), and 100% (25/25) of participants,
      respectively, high-level resistance for erythromycin and tetracyclines and
      intermediate to high resistance for clindamycin was present in 100% (30/30), 50%
      (15/30), 33% (10/30), 27% (8/30), and 52% (13/25) of participants, respectively.
      Total P acnes counts and counts of each resistant strain decreased by
      approximately 1 log after 1 week of treatment, by at least 1.5 log after 2 weeks
      of treatment, and by at least 2 log after 3 weeks of treatment, with no
      differences between resistant and susceptible strains or between highly resistant
      and low-level resistant strains. Benzoyl peroxide cleanser 6% effectively reduced
      resistant P acnes populations and offers a useful therapy for controlling
      antibiotic resistance in patients receiving antibiotics.

PMID- 19181033
TI  - Fluorescence (FISH) and chromogenic (CISH) in situ hybridisation in prostate
      carcinoma cell lines: comparison and use of virtual microscopy.
AB  - Chromogenic in situ hybridisation (CISH) has become an attractive alternative to
      fluorescence in situ hybridisation (FISH) due to its permanent stain which is
      more familiar to pathologists and because it can be viewed using light
      microscopy. The aim of the present study is to examine reproducibility in the
      assessment of abnormal chromosome number by CISH in comparison to FISH. Using
      three prostate cell lines--PNT1A (derived from normal epithelium), LNCAP and
      DU145 (derived from prostatic carcinoma), chromosomes 7 and 8 were counted in 40
      nuclei in FISH preparations (x100 oil immersion) and 100 nuclei in CISH
      preparations (x40) by two independent observers. The CISH slides were examined
      using standard light microscopy and virtual microscopy. Reproducibility was
      examined using paired Student's t-test (P<0.05). Reproducibility between
      observers was good for both FISH and CISH. No significant differences in
      chromosome count were seen between the techniques. Chromosomes 7 and 8 showed
      disomic status for each cell line except LNCAP, which proved to be heterogeneous
      (disomic/aneusomic), particularly for chromosome 8. Virtual microscopy proved to
      be easy to use and gave no significant differences from standard light
      microscopy. These results support the hypothesis that there is no significant
      difference between FISH and CISH techniques.

PMID- 19181034
TI  - Correlation of Bmi-1 expression and telomerase activity in human ovarian cancer.
AB  - This study investigates the correlation between the oncoprotein Bmi-1 and
      telomerase activity in ovarian cancer. A real-time polymerase chain reaction
      (PCR) method is used to detect the messenger RNA (mRNA) expression of Bmi-1
      protein in 47 ovarian epithelial cancer cases, and immunohistochemistry is used
      to detect Bmi-1 protein expression in the tissues. A modified telomeric repeat
      amplification protocol (TRAP) is used to detect telomerase activity. Western
      blotting is used to detect the expression of telomerase hTERT in the tissues
      studied. Compared to normal ovarian epithelial tissue, Bmi-1 protein in the 47
      ovarian epithelial cancer cases showed higher expression and was related to
      pathological grade and clinical stage. Significantly higher Bmi-1 levels were
      found among different clinocopathological types of the cancer (P<0.05). Grade G3
      cases expressed Bmi-1 at a higher rate (93.10%) than did grade G2 cases (61.11%).
      Expression in phase II and phase III cases was lower (66.67%) than in phase IV
      (92.31%). In ovarian epithelial cancer tissues, 87.23% (41/47) cases demonstrated
      positive telomerase activity, whereas no activity was observed in normal tissues.
      The majority (90.24%) of specimens with positive telomerase activity showed high
      Bmi-1 expression levels. Spearman correlation analysis indicated that expression
      of Bmi-1 protein correlated positively with elevated telomerase activity. Bmi-1
      protein is highly expressed in ovarian epithelial cancer tissues, and expression
      correlates with histological grade and clinical phase. Elevated Bmi-1 expression
      correlates closely with increased telomerase activity and plays a significant
      role in the pathogenesis of ovarian cancer.

PMID- 19181035
TI  - Comparative in vitro antimicrobial procedural efficacy for susceptibility of
      Staphylococcus aureus, Escherichia coil and Pseudomonas species to
      chloramphenicol, ciprofloxacin and cefaclor.
AB  - The present study assesses the reliability of the in vitro susceptibility tests E
      test, disc diffusion and Alamar blue-based microbroth dilution assays for
      evaluating the efficacy of chloramphenicol, ciprofloxacin and cefaclor against
      clinical and reference isolates of Staphylococcus aureus, Escherichia coli and
      Pseudomonas spp. for use in empirical therapy. Ciprofloxacin showed 82% agreement
      between E-test and microbroth dilution by the visible dye reduction method
      against all organisms. This figure was 67% for cefaclor and 60% for
      chloramphenicol. E-test and microbroth dilution showed excellent correlation
      against S. aureus with all three antibiotics; however, correlation was not
      observed in Pseudomonas spp. between E-test and microbroth dilution by the
      percentage dye reduction method. E. coli did not show significant correlation,
      indicating the presence of heteroresistance. Chloramphenicol, being bacteristatic
      in nature, did not show clear agreement between the susceptibility test methods
      used. This study indicates that E-test provides an indication of minimum
      inhibitory concentration (MIC) of a panel of antibiotics against clinical
      isolates; however, microbroth dilution (dye reduction) is the most sensitive
      method for the determination of MIC due to intracellular enzymatic reduction of
      the dye to formazan, which only occurs in viable organisms. The study highlights
      the need for harmonisation between E-test and microbroth dilution methods in
      clinical trials of new antibiotics and in monitoring the drug resistance patterns
      in community and healthcare settings.

PMID- 19181036
TI  - Reduction of Staphylococcus epidermidis adhesion to indwelling medical devices: a
      simple procedure.
AB  - The present study aims to find a method to reduce Staphylococcus epidermidis
      adhesion to acrylic and silicone--two materials used commonly in medical devices-
      by heparin and gentian violet surface preconditioning. Different periods of
      heparin preconditioning are studied to evaluate the influence of preincubation
      time on the reduction of bacterial adhesion. A two-hour period was chosen and
      applied in the adhesion assays with either heparin or gentian violet. Squares of
      the materials with adherent cells were also analysed by scanning electron
      microscopy (SEM). Results of adhesion assays showed a significant reduction (53
      90%, P<0.05) in bacterial adhesion to silicone and acrylic after precontact with
      the conditioning substances. No statistical differences (P>0.05) were found
      between the extent of adhesion on silicone coupons precontacted either with
      heparin or gentian violet for each of the strains tested. On acrylic, heparin was
      more efficient (P<0.001) in reducing S. epidermidis IE186 adhesion than was
      gentian violet (85% and 53% reductions, respectively). Therefore, immersion of
      acrylic and silicone in heparin or gentian violet may constitute a simple and
      effective method by which to reduce S. epidermidis adhesion to medical devices.

PMID- 19181037
TI  - Detection of ESBL bacteria from clinical specimens: evaluation of a new selective
      medium.
AB  - Selective screening media for extended-spectrum beta-lactamase (ESBL)-producing
      bacteria are needed to guide antibiotic therapy and institute appropriate
      infection control measures. This study evaluates a selective cefpodoxime
      incorporated chromogenic agar (CCA) medium for the detection of ESBLs from
      clinical specimens. The medium was formulated specifically for this study. For
      all culture-positive urine samples and wound swabs from intensive care unit (ICU)
      patients, CCA was compared with standard laboratory testing procedures and
      HPA/BSAC guidance on ESBL detection. The CCA medium was also evaluated for ESBL
      faecal carriage from patients on ICU and the haematology ward. These patients had
      no prior evidence of colonisation or infection with ESBL-producing bacteria. All
      ESBL isolates underwent minimum inhibitory concentration (MIC) testing to
      cefpodoxime. The Miles and Misra method and the ecometric methods were used to
      quality control the microbiological performance of the CCA medium, which proved
      satisfactory. A total of 750 specimens were examined (690 urines, 40 faeces, 20
      wound swabs). From urine cultures, 92 suspect colonies were followed up. Eighteen
      were cefpodoxime-resistant on routine disc testing and all were confirmed
      subsequently as ESBL-positive. Conventional laboratory methods identified only
      two urinary ESBLs. Wound cultures revealed two suspect colonies, both of which
      were ESBL-positive and were also detected by routine methods. Faecal samples
      produced 10 suspect colonies, six of which were ESBL-positive. All ESBLs had
      cefpodoxime MICs >10 mg /L (75% were >256 mg/L). Thus, primary conventional
      culture methods cannot be relied upon to detect suspect ESBL-producing bacteria.

PMID- 19181039
TI  - Application of microwave heat to paraffin sections: rapid adhesion of sections to
      slides.

PMID- 19181038
TI  - Cloning and structural analysis of the full-length cytolethal distending toxin
      (cdt) gene operon from Campylobacter lari.
AB  - Polymerase chain reaction (PCR) amplicons (approximately 2.5 kbp) encoding a cdt
      gene operon and two partial and putative open reading frames (ORFs) were
      identified in six urease-negative (UN) Campylobacter lari isolates using a new
      PCR primer pair constructed in silico. Three closely spaced and putative ORFs for
      cdtA, cdtB and cdtC, two putative promoters and a hypothetically intrinsic p
      independent transcription terminator were found in the operon. Each ORF commenced
      with an ATG start codon and terminated with a TGA stop codon for cdtA and cdtB
      and a TAA for cdtC. Interestingly, an overlap of four nucleotides was detected
      between cdtA and cdtB and the non-coding region of six base pairs occurring
      between cdtB and cdtC. The start codons for the three cdt genes were preceded by
      Shine-Dalgarno sequences. Although nucleotide sequence differences were
      identified at seven loci in the cdtA gene, six in cdtB and two in cdtC among the
      seven isolates (including C. lari RM2100), no polymorphic sites occurred in the
      putative promoters, hypothetically intrinsic transcription terminator and the
      three ribosome binding sites among the seven isolates. All nine amino acid
      residues specific for both Escherichia coli cdtB and mammalian DNase I were
      completely conserved in the cdtB gene locus in the 26 C. lari isolates, as well
      as in C. jejuni and C. coli. No PCR amplicons were generated with urease-positive
      thermophilic campylobacters (UPTC; n=10) using the primer pair.

PMID- 19181040
TI  - Should long-haul flights carry antibiotics on board to treat acute bacterial
      meningitis and meningococcal septicaemia?

PMID- 19181041
TI  - Mixed HSV-1 and HSV-2 infection in a patient attending a GUM clinic.

PMID- 19181042
TI  - Cell signalling is the music of life.
AB  - Cell signalling is an immensely important topic in biological and biomedical
      sciences, and one which has an ever-increasing literature. As more and more is
      known about it, and more components are discovered, it is getting harder and
      harder to visualise how it all might work to create an holistic mechanism in the
      cell. To achieve a better understanding of a complex issue such as this, it is
      often useful to use an analogy which is familiar to the researcher to encourage
      better understanding. In this essay it is suggested that music, and the
      instruments used to produce it, can be used as such an analogy. Various elements
      and issues in cell signalling are discussed and musical comparisons are made.
      Clearly, the true understanding of cell signalling will come from systems biology
      and mathematical modelling, but it is proposed that this analogy might prove
      useful. The phrasing used may be considered a little loose and flamboyant for a
      scientific topic of such importance, but it is hoped that the discussion will not
      only be interesting but might also be useful in fostering debate and facilitating
      teaching in this area of molecular biology.

PMID- 19181043
TI  - Good analytical practice: statistics and handling data in biomedical science. A
      primer and directions for authors. Part 1: Introduction. Data within and between
      one or two sets of individuals.
AB  - The biomedical scientist is bombarded on a daily basis by information, almost all
      of which refers to the health status of an individual or groups of individuals.
      This review is the first of a two-part article written to explain some of the
      issues related to the presentation and analysis of data. The first part focuses
      on types of data and how to present and analyse data from an individual or from
      one or two groups of persons. The second part will examine data from three or
      more sets of persons, what methods are available to allow this analysis (i.e.,
      statistical software packages), and will conclude with a statement on appropriate
      descriptors of data, their analyses, and presentation for authors considering
      submission of their data to this journal.

PMID- 19181044
TI  - Epidemiological sociology and the social shaping of population health.
AB  - When biomedical knowledge and technology create the capacity for humans to avoid
      disease and circumvent early death, sociological factors become more, not less
      important for population health. The transformation of disease causation from
      cruel fate, accident, and bad luck to circumstances that are under some degree of
      human control facilitates a powerful social shaping of disease and death. When
      humans have control, it is their policies, their knowledge, and their behaviors
      that shape the consequences of biomedical accomplishments, and thereby extant
      patterns of disease and death. I propose a "social shaping approach" that can
      frame our understanding of these processes and allow us to take action to
      optimize population health. Support for this approach is garnered from evidence
      of dramatic improvements in population health and in the uneven distribution of
      those improvements across persons, places, and times. Health improvements suggest
      that humans have gained control of disease whereas the uneven and very slow
      spread of such improvements underscores the critical importance of social
      factors. But the evidence presented represents a stick figure at best, one that
      needs to be filled in by a well-supported "epidemiological sociology" that uses a
      wide range of sociological concepts and theories to elucidate the social shaping
      of disease and death. Absent a robust societal investment in epidemiological
      sociology, population health will reside below its optimal level and the
      maldistribution of health-enhancing innovations will continue to create health
      disparities.

PMID- 19181045
TI  - Similar pressures, different contexts: public attitudes toward government
      intervention for health care in 21 nations.
AB  - Health care systems worldwide are experiencing similar pressures such as rising
      cost, aging populations, and increased burden of disease. While policy makers in
      all countries face these challenges, their responses must consider local
      pressures, particularly the implicit social contract between the state, medicine,
      and insurers. We argue that public attitudes provide a window into the social
      context in which policy decisions are embedded. Using data from the International
      Social Survey Programme (ISSP), we compare public attitudes toward government
      involvement in health care in 21 countries, testing the associations between
      various national-level variables (e.g., health care expenditures, aging of
      population, health care traditions) and public opinions. Specifically, we posit
      four national-level hypotheses ("health care traditions," "expenditure crisis,"
      "demographic crisis," "changing disease profile crisis"), one individual-level
      hypothesis ("individual vulnerability"), and two cross-level hypotheses
      ("cultural socialization" and "health care need"). Our findings indicate that
      public attitudes cluster around the historical organization of health care, but
      also relate to current economic and demographic realities. Individuals in
      countries adopting the "National Health Service Model" (the state directly
      provides health care but complete state control is absent) or the "Centralized
      Model" (the state directly provides health care and has much control) are more
      supportive of government involvement in health care than those in the "Insurance
      Model" (the state is limited to maintenance of the system) countries. However
      citizens in countries currently spending more on health care and having a greater
      burden of chronic illness are less supportive. Our results cast doubt on
      arguments that increased cost will result in a questioning of the contract
      between the state and citizens in the social provision of health care. We end by
      discussing implications for recent work in political sociology that highlights
      the importance of public attitudes.

PMID- 19181046
TI  - Schisms in the church: National Health Service systems and institutional
      divergence in England and Wales.
AB  - Since devolution, the four countries of the United Kingdom have pursued
      strikingly different National Health Service (NHS) reforms. While England created
      a supply-side market more radical than the previous internal market system, Wales
      moved to a softer version of the purchaser/provider split emphasizing localism.
      This article deploys institutional theory to analyze the forces shaping change,
      and describes the hybrid forms of economic organization emerging, including the
      economic regulation model implemented in England. The schism that has resulted in
      separate NHS subsystems warrants a different analysis from the more familiar
      phenomenon of infield divergence. We argue that schism was triggered by political
      regulatory influences rather than economic or other social institutional forces,
      and predict that other decentralized public health care systems may follow a
      similar path. While political-regulatory, normative, and cognitive institutional
      influences push in the same direction in Wales, the misalignment of political
      regulatory and normative elements in England looks set to result in a period of
      organizational turbulence.

PMID- 19181047
TI  - Pollution comes home and gets personal: women's experience of household chemical
      exposure.
AB  - We report on interviews conducted with participants in a novel study about
      environmental chemicals in body fluids and household air and dust. Interviews
      reveal how personal and collective environmental history influence the
      interpretation of exposure data, and how participants fashion an emergent
      understanding of environmental health problems from the articulation of science
      and experience. To the illness experience literature, we contribute a framework
      for analyzing a new category of embodied narratives--"exposure experience"--that
      examines the mediating role of science. We update social scientific knowledge
      about social responses to toxic chemicals during a period in which science alters
      public understanding of chemical pollution. This article is among the first
      published accounts of participants' responses to learning personal exposure data,
      research identified as critical to environmental science and public health. Our
      findings raise the importance of reporting even uncertain science and underscore
      the value of a community-based reporting strategy

PMID- 19181048
TI  - Health and sexual status in an urban gay enclave: an application of the stress
      process model.
AB  - In this article, I apply the stress process model as a framework to understand
      sexual sociality and its impact on health among urban gay men in a large North
      American gay enclave. Data consisting of in-depth interviews with 70 gay men
      coupled with three years of fieldwork demonstrate a sexual status order that
      privileges caucasian, middle-class men in their twenties and early thirties, and
      that disadvantages black and Asian men, men over 40 years of age, and poor men.
      Men with low sexual status faced significant stressors in the form of avoidance
      from others, stigmatization, and rejection. These stressors, in turn, taxed
      personal resources, including self-esteem, sense of social support, and sense of
      control, and they also negatively affected emotional states in the form of
      depression and anxiety. Finally, some low status men were unable to consistently
      negotiate condom use as a consequence of a history of field stressors and
      diminished personal resources. The results suggest that more work on sexual
      status structures and their connection to health is needed, both within gay
      enclaves and across a broader spectrum of sexual subcultures.

PMID- 19181049
TI  - The role of work group in individual sickness absence behavior.
AB  - The purpose of our two-year follow-up study was to examine the effect of the
      social components of the work group, such as group absence norms and cohesion, on
      sickness absence behavior among individuals with varying attitudes toward work
      attendance. The social components were measured using a questionnaire survey and
      data on sickness absence behavior were collected from the employers' records. The
      study population consisted of 19,306 Finnish municipal employees working in 1,847
      groups (78% women). Multilevel Poisson regression modeling was applied. The
      direct effects of work group characteristics on sickness absence were mostly
      insignificant. In contrast, both of the social components of a work group had an
      indirect impact: The more tolerant the group absence norms (at both individual-
      and cross-level) and the lower the group cohesion (at the individual level), the
      more the absence behavior of an individual was influenced by his or her attitude
      toward work attendance. We conclude that work group moderates the extent to which
      individuals with a liberal attitude toward work attendance actually engage in
      sickness absence behavior.

PMID- 19181050
TI  - Family antecedents and consequences of trajectories of depressive symptoms from
      adolescence to young adulthood: a life course investigation.
AB  - Using prospective data from 485 adolescents over a 10-year period, the present
      study identifies distinct segments of depressive symptom trajectories--a
      nonsignificant slope during adolescence and a significant negative slope during
      the transition to adulthood. The study hypothesized that different age-graded
      life experiences would differentially influence these depressive symptom growth
      parameters. The findings show that early stressful experiences associated with
      family-of-origin SES affect the initial level of depressive symptoms. Experiences
      with early transitional events during adolescence explain variation in the slope
      of depressive symptoms during the transition to adulthood. The growth parameters
      of depressive symptoms and an early transition from adolescence to adulthood
      constrain young adult social status attainment. Consistent with the life-course
      perspective, family-of-origin adversity is amplified across the life-course by
      successively contingent adverse circumstances involving life-transition
      difficulties and poor mental health. The findings also provide evidence for
      intergenerational transmission of social adversity through health trajectories
      and social pathways.

PMID- 19181051
TI  - Racial convergence in cigarette use from adolescence to the mid-thirties.
AB  - Cigarette smoking by whites and African Americans shows puzzling age differences:
      An African American advantage during the teen years no longer appears in mid
      adulthood. This study uses two data sets to examine whether the life-course
      change is real--and not due to misleading comparisons across different cohorts-
      and then whether the racial convergence is consistent with resource or stress
      arguments emphasizing, respectively, cessation among whites or late initiation
      among African Americans. First, multilevel growth models using data from the
      National Youth Survey-a prospective, longitudinal study of a randomly selected
      national sample of teens followed from ages 12 to 18 in 1977 to ages 26 to 34 in
      1992--reveal that the racial convergence in smoking prevalence over the life
      course among this cohort is due primarily to greater white cessation. Second,
      consecutive cross-sectional samples of the National Health Survey replicate the
      broad patterns found in the NYS and show that convergence in smoking trajectories
      by race has strengthened over time. Together the results most favor a resource
      explanation of the different life-course patterns of smoking among whites and
      African Americans.

PMID- 19181052
TI  - Mosquito fauna of Key Largo, Florida.
AB  - A total of 28 species of mosquitoes was collected in dry-ice-baited light traps
      on Key Largo, Florida during 2002-2004. Total number of mosquitoes increased each
      year during the study.

PMID- 19181053
TI  - Mosquitoes of the mangrove forests of India: part 7--an overview.
AB  - Parts 1 to 6 of this series on the mosquitoes of the mangrove forests of India
      dealt with the mosquito species recorded in the mangroves of Bhitarkanika,
      Sundarbans, Andaman and Nicobar islands, Coringa, Chorao and Vikhroli, and
      Kundapur and Kannur. This concluding part provides an overview of the
      distribution of the mosquito species in different mangrove forests, including the
      mangroves of Muthupet in Tamilnadu and the mangroves of Gulf of Kutch and Gulf of
      Kambhat in Gujarat, species collected as larvae, species in relation to the
      salinity of the larval habitats, species landing on humans for feeding in the
      mangroves, and the impact of habitat degradation on species diversity.

PMID- 19181054
TI  - Nonreproductive isolation among four allopatric strains of Anopheles sinensis in
      Asia.
AB  - To verify the genetic proximity of Anopheles sinensis strains in Korea, China,
      Japan, and Thailand, we established 5 iso-female lines, and investigated their
      genetic relationships by analyzing crossing tests and comparing the DNA sequences
      of rDNA internal transcribed spacer 2 (ITS2) and mitochondrial cytochrome c
      oxidase subunit 2 (CO2). The results of reciprocal and F1-hybrid crosses between
      Thailand Form B (X, Y2) with Japanese Form A (X, Y1), Japanese Form B with Korean
      Form B, and Korean Form B with Chinese Form B indicated that these strains were
      genetically compatible, providing viable progenies and completely synaptic
      polytene chromosomes. The sequences of ITS2 and CO2 among 10 Asian An. sinensis
      strains were almost identical to each other, and the sequence variation was very
      low (<0.6% in both regions). Based on the above results, it was confidently
      concluded that An. sinensis is a single cosmopolitan species even though its
      geographical distribution ranges are comparatively wide (>2000 mi) and that the
      malaria-vector abilities of the various strains may vary depending on their
      geographical origins.

PMID- 19181055
TI  - Digital image analysis to estimate numbers of Aedes eggs oviposited in
      containers.
AB  - Monitoring reproductive rates in experiments involving aedine mosquitoes is
      tedious and time demanding. Here, we demonstrate a protocol for rapid estimation
      of aedine mosquito egg number. The protocol uses ImageJ, a publicly available
      image analysis program developed at the U.S. National Institutes of Health. The
      method relies upon the oviposition behavior of Aedes (i.e., ovipositing on a
      moist substrate instead of water surface) and upon the contrast between dark
      colored aedine eggs and a light, uniformly colored paper that is used as an
      oviposition substrate. The results for 3 Aedes species show that, following the
      generation of separate calibration curves for each species, the protocol allows
      for the accurate and repeatable estimation of samples containing hundreds of
      aedine eggs. We discuss the use of the protocol for monitoring immature aedine
      populations in both laboratory and field applications.

PMID- 19181056
TI  - Potential for North American mosquitoes to transmit Rift Valley fever virus.
AB  - The rapid spread of West Nile viral activity across North America since its
      discovery in 1999 illustrates the potential for an exotic arbovirus to be
      introduced and widely established across North America. Rift Valley fever virus
      (RVFV) has been responsible for large outbreaks in Africa that have resulted in
      hundreds of thousands of human infections and major economic disruption due to
      loss of livestock and to trade restrictions. However, little is known about the
      potential for North American mosquitoes to transmit this virus should it be
      introduced into North America. Therefore, we evaluated selected mosquito species
      from the southeastern United States for their ability to serve as potential
      vectors for RVFV. Mosquitoes were fed on adult hamsters inoculated 1 day
      previously with RVFV. These mosquitoes were tested for infection and ability to
      transmit RVFV after incubation at 26 degrees C for 7-21 days. None of the species
      tested (Aedes taeniorhynchus, Ae. vexans, Culex erraticus, Cx. nigripalpus, Cx.
      quinquefasciatus, and Cx. salinarius) were efficient vectors after they fed on
      hamsters with viremias ranging from 10(4.1) to 10(6.9) plaque-forming units
      (PFU)/ml. However, Ae. taeniorhynchus, Ae. vexans, and Cx. erraticus all
      developed disseminated infections after they fed on hamsters with viremias
      between 10(8.5) and 10(10.2) PFU/ml, and both Ae. vexans and Cx. erraticus
      transmitted RVFV by bite. These studies illustrate the need to identify the
      ability of individual mosquito species to transmit RVFV so that appropriate
      decisions can be made concerning the application of control measures during an
      outbreak.

PMID- 19181057
TI  - A quantitative in vitro assay for chemical mosquito-deterrent activity without
      human blood cells.
AB  - We report that an aqueous solution containing 10(-3) M adenosine triphosphate
      (ATP) and citrate-phosphate-dextrose-adenine (CPDA-1) can effectively replace
      transfusable human red blood cells in an in vitro Klun and Debboun bioassay
      system for evaluating chemicals for mosquito feeding-deterrent activity, using
      either Aedes aegypti or Anopheles stephensi. These species fed with similar
      avidity through collagen membrane covering aqueous 10(-3) M ATP plus CPDA-1 or
      red blood cells in CPDA-1 supplemented with ATP. In a 2nd experiment, we
      evaluated the feeding-deterrent activity of N,N-diethyl-3-methylbenzamide and a
      newly discovered natural product chemical, (-)-isolongifolenone, against these 2
      mosquito species. We found that the feeding-deterrent efficacy of the 2 chemicals
      was similar whether the feeding stimulant was red blood cells supplemented with
      ATP or ATP alone with CPDA-1. Since the use of human red blood cells in bioassays
      raises important health and logistic issues, aqueous ATP with CPDA-1 is a
      reasonable alternative to human blood cells for routine in vitro chemical
      screening.

PMID- 19181058
TI  - Behavioral responses of catnip (Nepeta cataria) by two species of mosquitoes,
      Aedes aegypti and Anopheles harrisoni, in Thailand.
AB  - An investigation of the biological effect of catnip oil (Nepeta cataria L.) on
      the behavioral response of field collected Aedes aegypti and Anopheles harrisoni
      was conducted using an automated excitorepellency test system. Aedes aegypti
      showed significantly higher escape rates from the contact chamber at 5% catnip
      oil compared to other concentrations (P < 0.05). With Anopheles harrisoni, a high
      escape response was seen at 2.5% catnip oil from the contact chamber, while in
      the noncontact chamber a higher escape response was observed at a concentration
      of 5%. Results showed that this compound exhibits both irritant and repellent
      actions.

PMID- 19181059
TI  - Efficacy of novel updraft traps for collection of mosquitoes in Cairns,
      Australia.
AB  - We conducted trials in Cairns, Australia, to examine if novel updraft light traps
      collected significantly more mosquitoes than the Centers for Disease Control and
      Prevention (CDC) model 512 miniature light trap. Two new updraft traps, the
      Northern Australia Quarantine Strategy (NAQS) Mozzie Trap and a CDC updraft trap,
      both collected significantly more mosquitoes than the standard CDC light trap,
      with a mean CDC Trap Index (trap collections relative to paired standard CDC
      light trap collections) of 3.3 and 2.3, respectively. These traps both had large
      horizontal suction areas that increased the probability that attracted mosquitoes
      entered the trap updraft. However, if the CO2 source was located within the
      updraft of the CDC updraft trap, mosquito collections decreased considerably,
      indicating that placement of the bait is critical to trap performance. Creating
      an updraft by simply inverting the CDC trap body did not increase collections.
      The Mosquito Magnet X trap also did not collect significantly more mosquitoes
      than the CDC trap. Two CDC light traps sharing a 600 ml CO2/min gas line
      collected ca. 50% more mosquitoes than a single CDC trap baited with 600 ml
      CO2/min, suggesting that a single gas source could be used on a trap line
      consisting of multiple trap units. These studies suggest that the optimal trap
      design should incorporate a CO2 release system that lures mosquitoes to a large
      updraft within a bowl-shaped trap intake.

PMID- 19181060
TI  - Evaluation of the Mosquito Sentinel 360 trap in Florida residential environments.
AB  - The Mosquito Sentinel 360 (MS) trap was evaluated in back yards of 6 residences
      in and near Gainesville, FL. Carbon dioxide and blue-light-emitting diode
      modified Centers for Disease Control and Prevention (CDC) traps were utilized as
      a human substitute host to provide a measure of the effectiveness of the MS trap
      in reducing mosquito presence at the back door area of the houses. At 5 of the 6
      residences, a MS trap was operated with or without carbon dioxide, Lurex3 +
      octenol, or an experimental attractant. All MS traps were operated in tandem with
      a CDC trap, with the 6th site occupied only by a CDC trap. Over 67,000 mosquitoes
      from 19 species were recovered over the 12 trial days. Of these species,
      Anopheles crucians, An. quadrimaculatus, Coquillettidia perturbans, Culex
      erraticus, and Mansonia titillans were the predominant, nuisance, and medically
      important species captured and accounted for >92% of specimens recovered.
      Overall, attractant-modified MS traps captured more mosquitoes than the paired
      CDC trap. Carbon dioxide was found to greatly increase the capture of mosquitoes;
      however, the Lurex3 + octenol combination was significant with Cq. perturbans.
      All attractant-modified MS traps captured more Cx. erraticus and Ma. titillans
      than did the CDC, CO2-baited host mimic traps. The use of the MS 360 trap will
      undoubtedly require the addition of baits and perhaps the inclusion of a host
      masking or repellent approach to ensure protection from nuisance mosquitoes in
      residential environments.

PMID- 19181061
TI  - Riceland mosquito management practices for Anopheles quadrimaculatus larvae.
AB  - Two separate but related studies were conducted regarding management of Anopheles
      quadrimaculatus larval populations in commercial rice fields near Cleveland, MS,
      in 2004. Study 1 was to evaluate the effectiveness of 2 treatments of aerially
      applied ultra-low volume applications of Bacillus thuringiensis var. israelensis
      (Bti) against An. quadrimaculatus larvae in dense, high-canopy mid- to late
      season rice crop. Study 2 was to investigate the effect of preflood treatments of
      lambda-cyhalothrin (Karate), which is commonly used against rice water weevil
      (Lissorhoptrus oryzophilus), on An. quadrimaculatus larvae. Excellent initial,
      but short residual control (>99% control 1 day after treatment) was observed in
      the Bti-treated fields in both mid- and late-season rice. Little or no effect on
      mosquito larvae was observed in the lambda-cyhalothrin-treated fields. Results
      indicate that Bti can be effectively used by mosquito management personnel to
      control larval populations of An. quadrimaculatus in late-season rice fields;
      however, lambda-cyhalothrin did not effectively control larval An.
      quadrimaculatus when applied preflood to rice fields.

PMID- 19181062
TI  - Efficacy of vectobac DT and culinexcombi against mosquito larvae in unused
      swimming pools in Malindi, Kenya.
AB  - The efficacy and persistence of 2 bacterial larvicides, Vectobac-DT (Bacillus
      thuringiensis israelensis [Bti]) and CulinexCombi (Bti and Bacillus sphaericus
      [Bs]), were tested against Anopheles gambiae and Culex quinquefasciatus in
      temporarily unused swimming pools with rainwater in Malindi, Kenya. Pre- and
      posttreatment larval densities were recorded by sampling with the standard WHO
      dipping technique for 8 consecutive days. The larvicides were applied to the
      pools with a knapsack sprayer. The data showed that Vectobac-DT was highly
      effective against early instars of An. gambiae with 89% reduction within 24 h but
      not as effective against the early stages of Cx. quinquefasciatus with reduction
      of only 46%. CulinexCombi resulted in high mortalities to early instars of both
      species with over 97% reduction within 24 h, but showed a drastic reduction 48 h
      after application. Both Vectobac-DT and CulinexCombi were highly effective
      against late instars of both species, whereby Vectobac-DT persisted much longer
      than CulinexCombi. Anopheles gambiae was found to be more susceptible to both
      larvicides than Cx. quinquefasciatus. By their high efficacy and good persistence
      against mosquito larvae, both Vectobac-DT and CulinexCombi can be recommended for
      use in integrated mosquito control programs.

PMID- 19181063
TI  - Residual efficacy of field-applied permethrin, d-phenothrin, and resmethrin on
      plant foliage against adult mosquitoes.
AB  - Backpack sprayer applications of permethrin, d-phenothrin, and resmethrin to
      vegetation and plants at Anastasia Island, St. Augustine, FL, were evaluated for
      duration of residual efficacy against adult mosquitoes. All treatments produced
      100% mortality (24 h) of mosquitoes in test cages placed within the vegetation.
      At 48 h and 1 wk posttreatment, insecticide treatments resulted in 70-100%
      reduction of adult mosquitoes caught by Centers for Disease Control and
      Prevention traps baited with 1-octen-3-ol. Insecticide residues in excised leaves
      from both treated and control areas of the study sites were evaluated against
      adult female Culex quinquefasciatus by laboratory bioassay. Permethrin produced
      90% mortality up to 1 wk postapplication. Both d-phenothrin and resmethrin
      produced nearly this level of mortality for a much shorter duration of <48 h
      postapplication, with residual effects dropping significantly thereafter. Average
      insecticide concentrations in leaves were quantified by gas chromatography/mass
      spectroscopy, and some correlation was observed between chemical and biological
      results.

PMID- 19181064
TI  - Spray characterization of thermal fogging equipment typically used in vector
      control.
AB  - Droplet size spectra from different sprayers used to generate insecticide-laden
      fogs for controlling flying insects were measured by a laser diffraction
      instrument and Teflon-coated slides. The objectives of this work were to present
      not only information on spray-system droplet size generated by different
      sprayers, but to compare methodologies by which other similar systems can be
      evaluated and give applicators sprayer-system performance data. Data from 45
      replicated spray tests, comprising 11 sprayers and 5 pesticides, showed a wide
      range in the droplet size spectra produced. The volume median diameter
      measurements ranged from 2.6 to 75.5 microm for diesel-diluted sprays and from
      27.9 to 59.9 microm for water-diluted sprays. Similarly, the percent volume <20
      microm ranged between 12.0-100% and 8.5-30.7%, for diesel- and water-diluted
      sprays, respectively. The droplet sizes measured by the swinging slide and laser
      diffraction methods were not consistent. The information presented aids users in
      sprayer selection and operation to produce the specific droplet size spectra
      required for a particular application.

PMID- 19181065
TI  - Evaluation of an automatic-timed insecticide application system for backyard
      mosquito control.
AB  - Several manufacturers and pest management companies have begun to market and
      install outdoor automatically timed insecticide application systems that claim to
      provide an envelope of protection against host-seeking mosquitoes within a
      defined area, e.g., residential backyards. A typical system consists of a multi
      gallon reservoir attached to a continuous loop of plastic tubing with multiple
      single spray head nozzles. Nozzles are usually placed along the perimeter of a
      backyard in landscaping or other areas suitable for mosquito harborage. This
      array is then connected to a programmable electric pump set to automatically
      apply an insecticide at predetermined intervals. An operational field study was
      conducted to evaluate this technology using previously installed MistAway systems
      at.3 residences in northwestern Florida. This system applied a mist-like
      application of 0.05% AI synergized pyrethrins for 45 sec at dawn and again at
      dusk in each backyard. Twice-weekly collections from ABC suction light traps,
      baited with carbon dioxide, were used as the evaluation tool. Female mosquitoes
      from treatment backyards were compared with trap collections from 3 backyards
      without automatic misting systems used as controls. We found that weekly mosquito
      reduction was highly variable and ranged from 98% to 14% during the 35-wk study.
      Because the primary method of reduction by these application systems was not well
      understood, a MistAway system was installed in an outdoor simulated residential
      backyard to determine exposure pathway under controlled conditions with field
      cage and excised-leaf bioassays. Using laboratory-reared females of Aedes
      albopictus and Culex quinquefasciatus in those assays, we found that reduction by
      the MistAway system was primarily achieved by direct exposure of the mosquitoes
      to the insecticide application and not from residual deposits on treated
      vegetation.

PMID- 19181066
TI  - Suppression of Ixodes scapularis (Acari: Ixodidae) following annual habitat
      targeted acaricide applications against fall populations of adults.
AB  - Spring acaricide applications directed against nymphal Ixodes scapularis have
      been shown to be effective, but are perceived by the public as having significant
      adverse environmental impacts, particularly against nontarget organisms.
      Targeting the adult stage of I. scapularis in the fall would hypothetically
      result in indirect control of subsequent subadult stages while avoiding other
      arthropods that are typically inactive during this period. We demonstrate that
      single fall applications of deltamethrin for 3 consecutive years immediately
      reduced fall questing adults, while also rapidly reducing the abundance of all
      postembryonic stages. Deltamethrin applied to the shrub-layer vegetation resulted
      in levels of control between 97.1% and 100% at 7 days postapplication. Repeated
      applications against the reproductive stage of I. scapularis progressively
      reduced the abundance of larvae and nymphs in treated plots, reaching 91.4% and
      100% by the conclusion of the study.

PMID- 19181067
TI  - Mosquito vector control and biology in Latin America--an 18th symposium.
AB  - The 18th Annual Latin American symposium presented by the American Mosquito
      Control Association (AMCA) was held as part of the 74th Annual Meeting in Sparks,
      NV, in March 2008. The principal objective, as for the previous 17 symposia, was
      to promote participation in the AMCA by vector control specialists, public health
      workers, and academicians from Latin America. This publication includes summaries
      of 35 presentations that were given orally in Spanish or presented as posters by
      participants from 5 countries in Latin America and Puerto Rico. Topics addressed
      in the symposium included surveillance, chemical and biological control,
      insecticide resistance, and repellency of Aedes aegypti; distribution, behavior,
      transmission of West Nile virus, and control of Culex; bionomics, ecology, and
      chemical and biological control of Anopheles vectors of malaria; insecticide
      resistance; and studies of Triatoma and Rhodnius.

PMID- 19181068
TI  - First records of Aedes japonicus japonicus in Wisconsin.
AB  - Aedes japonicus japonicus was collected via gravid trapping in Wisconsin in the
      summers of 2004 and 2005 at Fort McCoy, Monroe County. Subsequently, in the
      summer of 2007, Ae. japonicus was captured in a human landing catch in Dane
      County, Madison, WI. Additional collections were made at this site in the spring
      of 2008. Invasion is in progress, but significant population increases have not
      yet been confirmed.

PMID- 19181070
TI  - Culex coronator in coastal Georgia and South Carolina.
AB  - In 2007, adult Culex coronator were collected in Chatham County, Georgia, and
      Jasper County, South Carolina, during nuisance and disease vector surveillance
      efforts. A total of 75 specimens of this species were collected at 8 widely
      separated locations in Chatham County, Georgia, and 4 closely situated sites in
      Jasper County, South Carolina. These represent the first Atlantic coastal records
      of this species in Georgia and the first confirmed records of Cx. coronator in
      South Carolina.

PMID- 19181069
TI  - Distribution expansion of Culex coronator in Alabama.
AB  - Culex coronator, a mosquito species common to the American tropics, has been
      recently documented from a number of temperate areas in the USA. Since 2002
      specimens have been reported for the first time from Oklahoma, Louisiana,
      Mississippi, Alabama, and Florida. Here we provide new collection records for Cx.
      coronator in east-central Alabama. In October 2007, 2 larvae of Cx. coronator
      were collected from an artificial container in Tuskegee National Forest in Macon
      County, AL. The distribution of Cx. coronator in the USA seems to be expanding at
      a prodigious rate, for reasons that remain unclear.

PMID- 19181071
TI  - Laboratory colonization of Aedes japonicus japonicus.
AB  - We describe methodology used for the laboratory colonization of Aedes japonicus
      japonicus, an exotic mosquito species native to eastern Asia and first collected
      in New Jersey as larvae in 1999. We created a free mating colony in 2000 that
      readily bloodfed on restrained bobwhite quail (Colinus virginianus). A larval
      diet of finely ground Purina Lab Diet dissolved in dechlorinated water has proven
      acceptable. This is the first report of Ae. j. japonicus colonization from
      mosquitoes collected in the United States.

PMID- 19181072
TI  - Controlled release chamber for dispensing aromatic substances.
AB  - A novel device for the containment and precise release of aromatic substances is
      described. The device consists of a threaded-tubular polyvinyl chloride chamber
      (and screw-top cap) with ports for introduction and release of gaseous compounds.
      This chamber is inexpensive, easy to assemble, and useful for evaluating the
      combined release of carbon dioxide and aromatic hygroscopic substances as
      mosquito attractants in field studies.

PMID- 19181073
TI  - Evaluation of the inhibition of egg laying, larvicidal effects, and bloodfeeding
      success of Aedes aegypti exposed to permethrin- and bifenthrin-treated military
      tent fabric.
AB  - Laboratory studies were conducted to evaluate the effects of treating military
      canvas tent fabric with bifenthrin and permethrin on the survival of the eggs and
      larvae of Aedes aegypti. Gravid female Ae. aegypti were able to oviposit on tent
      canvas treated with either bifenthrin or permethrin. However, none of the eggs
      laid on treated canvas hatched, and no larvae added to water in treated trays
      survived. Low residual concentrations of bifenthrin and permethrin on treated
      canvas prevented the development of eggs and larvae of Ae. aegypti. Inhibition of
      bloodfeeding was shown when Ae. aegypti adults were exposed to lower
      concentrations (10-50% of operational concentrations) of bifenthrin- and
      permethrin-treated canvas tent fabric. These experiments have shown that military
      tent canvas treated with either bifenthrin or permethrin can reduce the
      development of Ae. aegypti eggs and larvae and reduce bloodfeeding success of
      adults.

PMID- 19181074
TI  - Discovery of diurnal resting sites of phlebotomine sand flies in a village in
      southern Egypt.
AB  - In an attempt to find diurnal resting sites of adult phlebotomine sand flies,
      potential phlebotomine adult habitats were aspirated in the village of Bahrif in
      Aswan, Egypt. During this survey, sand flies were aspirated from low (30-45 cm
      high) irregular piles of mud bricks found under high date palm canopies between
      the village and the Nile River. There were 5 males and 7 females of Phlebotomus
      papatasi and 3 males of Sergentomyia schwetzi. Six of the 7 aspirated females
      were engorged with blood. A total of 78 sand flies was captured on 3 glue boards
      placed overnight on the ground next to the mud bricks. Attempts to aspirate sand
      flies from adjacent walls and plants were unsuccessful. The identification of
      diurnal resting sites in less structured habitats may ultimately lead to more
      effective adult sand fly control.

PMID- 19181075
TI  - Sampling of adult mosquito vectors with Mosquito Magnet Pro in Panaji, Goa,
      India.
AB  - For mosquito vector population monitoring, a new commercial trap, Mosquito Magnet
      Pro (MM-PRO), was tested for its usefulness in Goa, India. Anopheles stephensi
      was tested for the presence of Plasmodium sporozoite infection in the salivary
      glands. Using the MM-PRO 24 h a day for 34 days, 2,329 mosquitoes belonging to 16
      species were collected. These included 6 species each of the genera Anopheles and
      Culex, 2 species of Aedes, and 1 each of Mansonia and Armigeres. Most (91%) of
      the mosquitoes caught were females. Among these the number and percentage of each
      species were Anopheles stephensi 59 (2.78%), Culex quinquefasciatus 1013
      (47.78%), Culex vishnui 551 (26.0%), Mansonia uniformis 216 (10.19%), and Aedes
      albopictus 1 (0.04%). Of the 54 An. stephensi females tested for the presence of
      circumsporozoite protein (CSP) by an ELISA technique, 1 was found to be
      Plasmodium falciparum CSP positive. The MM-PRO device was found useful for
      mosquito population sampling in the urban setting of Goa.

PMID- 19181076
TI  - Aedes aegypti resistance to temephos in Argentina.
AB  - Monitoring of resistance of Aedes aegypti to temephos was implemented in the
      provinces of Formosa and Misiones, Argentina, as a response to the need to
      improve the vigilance for the dengue vector in areas of high risk of dengue. Eggs
      collected in each locality were reared, and susceptibility to temephos was
      assayed using larval bioassays. A weak decrease in susceptibility of larvae to
      temephos was observed in Clorinda and Puerto Iguazu, indicating an incipient
      resistance with a resistance ratio of 3. No control failures have been observed
      yet, and this program should allow the early detection of a real problem in our
      country.

PMID- 19181077
TI  - Memorial lecture honoring professor Andrew Spielman.

PMID- 19181078
TI  - IT winners and losers in 2009.

PMID- 19181079
TI  - Squeezing more from IT.

PMID- 19181080
TI  - Riding the painted ponies.

PMID- 19181081
TI  - Identity in the palm of your hand.

PMID- 19181082
TI  - Fewer stacks, fewer gaps.

PMID- 19181083
TI  - Disease management mobilized.

PMID- 19181084
TI  - Rapid response, better outcomes.

PMID- 19181085
TI  - ePrescribing: ready for prime time. But is your government?

PMID- 19181086
TI  - Congressman John Yarmuth--Keynote Address Kentucky Nurses Association Convention
      2008.

PMID- 19181087
TI  - Preparing for CNE certification: a journey to excellence.

PMID- 19181088
TI  - Foreword. Sarcomeric disease: advances and some unanswered questions.

PMID- 19181089
TI  - The sarcomere and sarcomerogenesis.
AB  - Striated muscle owes its name to the microscopic appearance, caused by the
      longitudinal alignment of thousands of highly ordered contractile units, the
      sarcomeres. The assembly (and disassembly) of these multiprotein complexes
      (sarcomere assembly or sarcomerogenesis) follows ordered pathways, which are
      regulated on the transcriptional, translational and posttranslational level.
      Furthermore, myofibril assembly involves the participation of transient scaffolds
      and adaptors, notably the microtubule network. Studies in cell culture and
      developing embryos have revealed common pathways of sarcomere assembly in heart
      and skeletal muscle. Disruptions in these pathways are implicated in muscle
      diseases.

PMID- 19181090
TI  - Skeletal muscle alpha-actin diseases.
AB  - Skeletal muscle alpha-actin is the principal protein component of the adult
      skeletal muscle thin filament. The interaction between skeletal muscle alpha
      actin and the various myosin heavy chain proteins in the different muscle fibre
      types generates the force of muscle contraction. Skeletal muscle alpha-alpha
      actin is thus of fundamental importance to normal muscle contraction. To date
      over 140 different disease-causing mutations have been identified in the skeletal
      muscle alpha-actin gene ACTA1. These mutations are associated with histologically
      distinct congenital myopathies, including nemaline myopathy, actin myopathy,
      intranuclear rod myopathy, congenital fibre type disproportion and myopathy with
      cores. Mutations in ACTA1 are associated with a wide range of clinical severity
      although the majority of patients tend to have severe congenital-onset disease.
      Most of the patients have de novo dominant mutations not present in either
      parent. However mild ACTA1 disease may be dominantly inherited and there are also
      recessive mutations. The recessive mutations are either genetic or functional
      null mutations. Patients with no skeletal actin retain cardiac actin, the fetal
      isoform of actin in skeletal muscle. Information from the clinic suggests that
      exercise and L-tyrosine may benefit some patients and that in the future
      decreasing the proportion of mutant actin may ameliorate the disease in some
      patients.

PMID- 19181091
TI  - Nebulin--a giant chameleon.
AB  - Nebulin is an enormous protein of the muscle sarcomere. It is a determinant of
      thin filament length, Z-disk structure and fiber contractility. The nebulin gene
      contains four regions of alternative splicing, providing a wealth of different
      isoforms of the protein. The precise function of these numerous isoforms in
      various types of muscle tissue remains to be elucidated, as does their role in
      the maintenance of normal muscle strength and activity. Understanding these basic
      mechanisms is a prerequisite for the development of specific therapies for the
      disorders caused by mutations in the nebulin gene. Such mutations are the main
      cause of autosomal recessive nemaline (rod) myopathy, especially of the typical
      form of this congenital myopathy. Further known disorders caused by nebulin
      mutations are several other subcategories of recessively inherited nemaline
      myopathy and a novel distal myopathy caused byhomozygous missense mutations in
      the nebulin gene. Because of the giant size of the gene, molecular genetic
      testing methods are difficult to design for routine diagnostic use.

PMID- 19181092
TI  - Skeletal muscle disease due to mutations in tropomyosin, troponin and cofilin.
AB  - Tropomyosin (Tm) and the troponins (troponin I, troponin T and troponin C) are
      proteins that work cooperatively to regulate muscle contraction, making actin
      myosin interactions sensitive to cytosolic calcium levels. Several isoforms exist
      for each component in this group, each having a specific expression pattern that
      enables cardiac, slow skeletal (type 1) and fast skeletal (type 2) muscle fibers
      to have distinct contractile properties. Mutations in all components of this
      complex have been associated with skeletal muscle disease. The first disease
      associations were with nemaline myopathy, but recently other congenital
      myopathies ('cap disease', congenital fiber type disproportion) and other
      clinical entities (distal arthrogryposis, multiple pterygium syndrome) have been
      linked to mutations. A homozygous mutation in CFL2, the gene for muscle cofilin,
      has been associated with nemaline myopathy in one family to date. Researchers
      have begun to decipher the mechanisms by which these mutations result in muscle
      weakness and contractures using a variety of in vitro assays to assess the
      effects of individual mutations on protein function and on sarcomere dynamics.

PMID- 19181093
TI  - Investigations into the pathobiology of thin-filament myopathies.
AB  - Mutations in actin and tropomyosin, identified in patients with myopathic disease
      have been used in tissue culture models and functional studies with a view to
      understand how these mutations impact on skeletal muscle structure and function
      and result in muscle weakness. The likely mode of pathogenesis in these disorders
      is via a dominant negative effect i.e., the production of 'poison' proteins that
      interfere with the normal function of the native protein. Tissue culture models
      and in vitro binding studies highlight the defects of different actin mutants
      including abnormal folding, aggregation and altered polymerization which would
      likely impact on skeletal muscle structure and function. The most widely studied
      mutation in tropomyosin is the M9R substitution identified in a large Australian
      family with nemaline myopathy. The M9R mutant protein has a reduced affinity for
      actin, does not bind to tropomodulin in a model peptide and results in reduced
      sensitivity of isometric force to activating calcium in cardiac myocytes. The
      pathological consequences of mutations identified in troponin, nebulin, and
      cofilin are also discussed. Although mutations in alpha-actinin have not been
      associated with NM, tissue culture models using tagged constructs of different
      regions of the alpha-actinin gene suggest that this protein plays a role in
      nemaline body formation.

PMID- 19181094
TI  - Mouse models for thin filament disease.
AB  - Thin filament integrity is important for the ordered structure and function of
      skeletal muscles. Mutations within genes that encode thin filament and thin
      filament-associated proteins can cause muscle disruption, fiber atrophy and alter
      fiber type composition, leading to muscle weakness. Analyses of patient biopsy
      samples and tissue culture systems provide rapid methods for studying disease
      causing mutations. However, there are limitations to these techniques. Although
      time consuming, many laboratories are generating and utilizing animal models, in
      particular the mouse, to study the disease process of various myopathies. This
      chapter reviews the use of mouse models for thin filament diseases of skeletal
      muscle and in particular, concentrates on what has been achieved through the
      generation and characterization of transgenic and knock-in mouse models for the
      congenital thin filament disease nemaline myopathy. We will review potential
      therapies that have been trialled on the nemaline models, providing indications
      for future directions for the treatment of nemaline myopathy patients and muscle
      weakness in general.

PMID- 19181095
TI  - Thick filament diseases.
AB  - Hereditary myosin myopathies are a newly emerged group of diseases caused by
      mutations in skeletal muscle myosin heavy chain (MyHC) genes. The phenotypes of
      these diseases are varied, ranging from prenatal nonprogressive arthrogrypotic
      syndromes to adult-onset progressive muscle weakness. They are caused by
      mutations in skeletal muscle myosin heavy chain (MyHC) genes. Mutations have been
      reported in two of three MyHC isoforms expressed in adult limb skeletal muscle:
      type I (slow/beta-cardiac MyHC; MYH7) and type IIa (MYH2). Most of the mutations
      described in MYH7are associated with hypertrophic/dilated cardiomyopathy, with no
      skeletal muscle involvement. However, some mutations are associated with two
      distinct skeletal myopathies, namely Laing distal myopathy and myosin storage
      myopathy. Although initially thought not to have associated cardiac involvement,
      recent reports have indicated co-existent cardiac and skeletal muscle disease can
      occur in both. A myopathy associated with a specific mutation in MYH2 is
      associated with congenital joint contractures and external ophthalmoplegia.
      Mutations in embryonic MyHC (MYH3) and perinatal MyHC (MYH8) are associated with
      distal arthrogryposis syndromes with no or minor muscle weakness. This may be
      expected in myosin isoforms expressed predominantly during muscle development.
      Clinical findings, muscle morphology and molecular genetics in hereditary myosin
      myopathies are summarized in this chapter.

PMID- 19181096
TI  - Acute quadriplegic myopathy: an acquired "myosinopathy".
AB  - Acquired neuromuscular disorders have been shown to be very common in critically
      ill patients receiving prolonged mechanical ventilation in the intensive care
      unit (ICU). Acute Quadriplegic Myopathy (AQM) is a specific acquired myopathy in
      ICU patients. Patients with AQM are characterized by severe muscle weakness and
      atrophy of spinal nerve innervated limb and trunk muscles, while cranial nerve
      innervated craniofacial muscles, sensory and cognitive functions are spared or
      less affected. The muscle weakness is associated with altered muscle membrane
      properties and a preferential loss of the motor protein myosin and myosin
      associated thick filament proteins. Prolonged mechanical ventilation, muscle
      unloading, postsynaptic block of neuromuscular transmission, sepsis and systemic
      corticosteroid hormone treatment have been suggested as important triggering
      factors in AQM. However, the exact mechanisms underlying the loss of thick
      filament proteins are not known, though enhanced myofibrillar protein degradation
      in combination with a downregulation of protein synthesis at the transcriptional
      level play important roles.

PMID- 19181097
TI  - Third filament diseases.
AB  - The backbone of the third filament system of the sarcomere is the huge titin
      molecule, spanning from the sarcomeric Z-disc to the M-line. Proteins in direct
      interaction and functionally integrated with titin, such as calpain 3 and
      telethonin, are part of the third filament system. The third filament system
      provides support to the contractile filament systems during development and
      mature states including mechanical properties and regulatory signaling functions.
      The first mutations in the third filament system causing human muscle disease
      were identified in calpain 3 in 1995, followed by telethonin and titin. In spite
      of some early ideas on what is going wrong in the muscle cells based on the
      defective proteins, the exact molecular pathomechanisms leading to muscle atrophy
      in patients with these disorders are still unknown. However, preparations for
      direct trials of gene therapy have already been launched, at least for
      calpainopathy.

PMID- 19181098
TI  - The Z-disk diseases.
AB  - Recent studies have identified disease-causing mutations in four genes that
      encode Z-disk proteins. Mutations in myotilin (MYOT), ZASP and filamin C (FLNC)
      encoding genes cause autosomal dominant myopathy that manifests in adulthood. The
      clinical features and morphological changes in myopathies caused by mutations in
      all three genes are highly similar. The disease typically manifests as distal
      myopathy, but may also affect proximal muscles and the heart. The morphological
      findings are typical of myofibrillar myopathy (MFM) and include Z-disk
      alterations and aggregation of dense filamentous material visible in trichrome
      staining. The disease mechanism is still unclear, but may involve structural
      alterations of the Z-disk caused by dysfunctional proteins or their abnormal
      accumulation due to defective degradation. Although the fourth gene product,
      telethonin, is also involved in the Z-disk organization, its mutations cause a
      different phenotype. Telethonin mutations result in recessive muscular dystrophy,
      which manifests in childhood as proximal weakness. The morphologic alterations
      caused by telethonin mutations are not well characterized, but may share common
      features of MFM. Future work aims at understanding the pathophysiology of Z-disk
      related disorders and identification of novel genetic defects in patients with
      morphological features of MFM.

PMID- 19181100
TI  - Muscular integrity--a matter of interlinking distinct structures via plectin.
AB  - Myocytes are characterized by the presence of highly specialized cytoskeletal
      structures that are part of regularly spaced functional units distributed over
      long distances. In this chapter we discuss previously published evidence as well
      as novel data showing that the proper positioning and architecture of Z-disks and
      of sarcolemma-associated costameric structures are largely dependent on the
      cytolinker protein plectin and its associated intermediate filament (desmin)
      cytoskeleton. Deficiency in either plectin or desmin lead to muscular dystrophies
      of similar pathology. However, while in the absence of plectin, desmin networks
      collapse and form aggregates, when desmin is missing, plectin retains its typical
      localization. This suggests that plectin recruits and anchors desmin filaments to
      both Z-disks and costameres and thus is a key element for maintaining and
      reinforcing myocyte cytoarchitecture. We hypothesize that as an essential link of
      the Z-disk-costamere axis, plectin is likely to play also a crucial role in
      myofiber signaling.

PMID- 19181099
TI  - Intermediate filament diseases: desminopathy.
AB  - Desminopathy is one of the most common intermediate filament human disorders
      associated with mutations in closely interacting proteins, desmin and alphaB
      crystallin. The inheritance pattern in familial desminopathy is characterized as
      autosomal dominant or autosomal recessive, but many cases have no family history.
      At least some and likely most sporadic desminopathy cases are associated with de
      novo DES mutations. The age of disease onset and rate of progression may vary
      depending on the type of inheritance and location of the causative mutation.
      Typically, the illness presents with lower and later upper limb muscle weakness
      slowly spreading to involve truncal, neck-flexor, facial and bulbar muscles.
      Skeletal myopathy is often combined with cardiomyopathy manifested by conduction
      blocks, arrhythmias and chronic heart failure resulting in premature sudden
      death. Respiratory muscle weakness is a major complication in some patients.
      Sections of the affected skeletal and cardiac muscles show abnormal fibre areas
      containing chimeric aggregates consisting of desmin and other cytoskeletal
      proteins. Various DES gene mutations: point mutations, an insertion, small in
      frame deletions and a larger exon-skipping deletion, have been identified in
      desminopathy patients. The majority of these mutations are located in conserved
      alpha-helical segments, but additional mutations have recently been identified in
      the tail domain. Filament and network assembly studies indicate that most but not
      all disease-causing mutations make desmin assembly-incompetent and able to
      disrupt a pre-existing filamentous network in dominant-negative fashion. AlphaB
      crystallin serves as a chaperone for desmin preventing its aggregation under
      various forms of stress; mutant CRYAB causes cardiac and skeletal myopathies
      identical to those resulting from DES mutations.

PMID- 19181101
TI  - The sarcomere and the nucleus: functional links to hypertrophy, atrophy and
      sarcopenia.
AB  - Skeletal muscle has a remarkable ability to rapidly adjust to changes in
      physiological requirements. This includes hypertrophic muscle growth and the
      atrophic loss of muscle mass, both of which occur in response to hormonal,
      endocrine and mechanical stimuli. In ageing muscle, sarcopenia (the loss of
      muscle fibres) can aggravate hormonally and mechanically induced atrophy.
      Hypertrophy and atrophy are associated with changes in sarcomeric protein
      composition and metabolic enzymes. The coordinated changes of transcriptional and
      splice mechanisms, protein turnover and cell fate integrates signalling pathways
      from hormone and cytokine receptors, as well as the sarcomere itself. This
      involves a number of proteins that shuttle between sarcomeric and nonsarcomeric
      localisations and thus convey signals from the contractile machinery to the
      nucleus. The M-band is emerging as a hub mainly for protein-kinase regulated
      ubiquitin signalling and protein turnover, whereas the I-band and Z-disk contain
      stretch-sensitive pathways involving transcriptional modifiers. Disruptions of
      these pathways can cause hereditary myopathies.

PMID- 19181103
TI  - Therapeutic approaches for the sarcomeric protein diseases.
AB  - No curative treatment currently exists for patients with skeletal myopathies
      caused by defects in sarcomeric proteins though symptomatic treatments including
      orthoses, night-time ventilation, or mechanical ventilation can provide major
      benefits. The molecular genetic discovery era has enabled many families to know
      which gene and precisely which gene defect their family, or in some cases only
      their affected child has. This knowledge has enormously increased the accuracy of
      genetic counselling and in some cases can enable prognosis, which helps families
      to make better-informed life decisions. However, symptomatic treatments and
      molecular genetics do not help the patient's skeletal muscle problems. The
      patients with skeletal muscle sarcomeric protein diseases, (from severely
      affected patients with shortened lifespan, through to the more mildly affected
      patients), would all benefit from more effective or curative treatments, as would
      their parents and families. This chapter outlines the experimental therapeutic
      strategies that have been investigated for other muscle diseases (predominantly
      the muscular dystrophies, towards which the majority of research emphasis has
      been focussed) and those that are beginning to be investigated for sarcomeric
      diseases. It analyses which of these approaches might be applicable to the
      different skeletal muscle sarcomeric protein diseases.

PMID- 19181104
TI  - Molecular mechanisms of xeroderma pigmentosum. Preface.

PMID- 19181105
TI  - Historical aspects of xeroderma pigmentosum and nucleotide excision repair.
AB  - The discovery that xeroderma pigmentosum was a sun-sensitive hereditary human
      disease that was deficient in DNA repair was made when research into the
      fundamental mechanisms of nucleotide excision repair was in its infancy. The
      linkage between DNA damage, DNA repair and human cancer stimulated an enormous
      subsequent growth of the field of DNA repair and the identification of other
      repair deficient diseases and other repair pathways. This growth has established
      DNA repair as a central factor for maintaining genomic stability and preventing
      cancer, neurodegenerative disease and aging. The study of DNA repair impacts many
      other areas including human genetics, signal transduction, protein structure, DNA
      protein interactions, DNA replication and recombination, transcription, telomere
      maintenance, development, differentiation, ecology and evolution.

PMID- 19181102
TI  - Other model organisms for sarcomeric muscle diseases.
AB  - Model organisms are vital to our understanding of human muscle biology and
      disease. The potential of the nematode Caenorhabditis elegans, the fruitfly,
      Drosophila melanogaster and the zebrafish, Danio rerio, as model genetic
      organisms for the study of human muscle disease is discussed by examining their
      muscle biology, muscle genetics and development. The powerful genetic tools
      available with each organism are outlined. It is concluded that these organisms
      have already demonstrated potential in facilitating the study of muscle disease
      and in screening for therapeutic agents.

PMID- 19181106
TI  - Clinical features of xeroderma pigmentosum.

PMID- 19181107
TI  - Xeroderma pigmentosum and skin cancer.
AB  - The hypersensitivity of DNA repair deficient xeroderma pigmentosum (XP) patients
      to solar irradiation results in the development of high levels of squamous and
      basal cell carcinomas as well as malignant melanomas in early childhood. Indeed,
      XP presents a unique model for analysing the effects of unrepaired DNA lesions in
      skin carcinogenesis. The skin cancer predisposition, observed in XP patients, is
      due to the mutator gene activity of XP cells which lead to high levels of UV
      specific modifications of crucial regulatory genes in skin cells leading to
      Cancer. Thus, the high levels of UV specific mutations, seen in oncogenes and
      tumor suppressor genes, which have been characterized in XP tumors, clearly
      demonstrate the major role of the UV component of sunlight in skin cancer
      development. The UV specific C to T and the tandem CC to TT UV signature
      transition mutations found in XP tumors are located at bipyrimidine sequences,
      the preferred UV targets in DNA. The same UV specific alterations are seen in key
      regulatory genes in sporadic skin cancers but at lower frequencies than those
      found in XP tumors.

PMID- 19181108
TI  - XPA gene, its product and biological roles.
AB  - The 31 kDa XPA protein is part of the core incision complex of the mammalian
      nucleotide excision repair (NER) system and interacts with DNA as well as with
      many other NER subunits. In the absence of XPA, no incision complex can form and
      no excision of damaged DNA damage occurs. A comparative analysis of the DNA
      binding properties in the presence of different substrate conformations indicated
      that XPA protein interacts preferentially with kinked DNA backbones. The DNA
      binding domain of XPA protein displays a positively charged deft that is involved
      in an indirect readout mechanism, presumably by detecting the increased negative
      potential encountered at sharp DNA bends. We propose that this indirect
      recognition function contributes to damage verification by probing the
      susceptibility of the DNA substrate to be kinked during the assembly of NER
      complexes.

PMID- 19181109
TI  - XPB and XPD between transcription and DNA repair.

PMID- 19181110
TI  - XPC: its product and biological roles.
AB  - The XPC protein is a component of a heterotrimeric complex that is essential for
      damage recognition in a nucleotide excision repair subpathway that operates
      throughout the genome. Biochemical analyses have revealed that the broad
      substrate specificity of this repair system is based on the structure-specific
      DNA binding properties of the XPC complex. Other subunits of this complex,
      including human Rad23p orthologs and centrin 2, play individual roles in
      enhancing the damage recognition activity of XPC. Physical interaction with UV
      damaged DNA-binding protein is also important for the efficient recruitment of
      XPC to sites containing DNA damage, particularly UV-induced photolesions.
      Furthermore, recent studies have suggested that XPC may also be involved in base
      excision repair and possibly in other cellular functions that may be mediated by
      posttranslational modifications.

PMID- 19181111
TI  - The XPE gene of xeroderma pigmentosum, its product and biological roles.

PMID- 19181112
TI  - XPF/ERCC4 and ERCC1: their products and biological roles.
AB  - ERCC4 is the gene mutated in XPF cells and also in rodent cells representing the
      mutant complementation groups ERCC4 and ERCC 11. The protein functions
      principally as a complex with ERCC1 in a diversity of biological pathways that
      include NER, ICL repair, telomere maintenance and immunoglobulin switching.
      Sorting out these roles is an exciting and challenging problem and many important
      questions remain to be answered. The ERCC1/ERCC4 complex is conserved across most
      species presenting an opportunity to examine some functions in model organisms
      where mutants can be more readily generated and phenotypes more quickly assessed.

PMID- 19181114
TI  - Xeroderma pigmentosum variant, XP-V: its product and biological roles.

PMID- 19181113
TI  - XPG: its products and biological roles.
AB  - Xeroderma pigmetosum patients of the complementation group G are rare. One group
      of XP-G patients displays a rather mild and typical XP phenotype. Mutations in
      these patients interfere with the function of XPG in the nucleotide excision
      repair, where it has a structural role in the assembly of the preincision complex
      and a catalytic role in making the incision 3' to the damaged site in DNA.
      Another set of XP-G patient is much more severely affected, displaying combined
      symptoms of xeroderma pigmentosum and Cockayne syndrome, referred to as XP/CS
      complex. Although the molecular basis leading to the XP/CS complex has not yet
      been fully established, current evidence suggests that these patients suffer from
      a mild defect in transcription in addition to a repair defect. Here, the history
      of how the XPG gene was discovered, the biochemical properties of the XPG protein
      and the molecular defects found in XP-G patients and mouse models are reviewed.

PMID- 19181116
TI  - The nucleotide excision repair of DNA in human cells and its association with
      xeroderma pigmentosum.

PMID- 19181117
TI  - Roles of oxidative stress in xeroderma pigmentosum.
AB  - Tissue damage caused by oxidative stress has been implicated in aging,
      carcinogenesis, atherosclerosis and neurodegeneration. In xeroderma pigmentosum
      (XP) and Cockayne syndrome (CS), oxidative stress is associated with promoted
      occurrence of skin cancers and progressive neurodegeneration, because decreased
      DNA repair and persistent DNA damage can result in augmented oxidative nucleotide
      damage. Oxidative nucleotide damage has been investigated mainly in isolated
      human skin and blood cells or their cell lines, in which CS cells may be more
      sensitive to oxidative DNA lesions than XP cells. However, cells from patients
      with XP group A (XPA) show defective repair of 8, 5'-(S)-cyclo-2'-deoxyadenosine,
      a free radical-induced endogenous DNA lesion and antioxidant system seems to be
      disturbed variously in cells from XP patients. We have neuropathologically
      investigated the involvement of oxidative stress in the brains of XPA and CS
      autopsy cases and clarified the enhanced lipid peroxidation and protein glycation
      in the pallidal and cerebellar degeneration. Also, oxidative nucleotide damage
      with reduced expression of superoxide dismutases has been identified in the basal
      ganglia lesions, lending further weight involvement of oxidative stress in
      neurodegeneration in XPA patients. Additionally, we are developing ELISA analysis
      of oxidative stress markers in the urine and cerebrospinal fluid from XP
      patients, which will aid with further data on oxidative stress in pathogenesis of
      XP.

PMID- 19181115
TI  - Other proteins interacting with XP proteins.

PMID- 19181118
TI  - Xeroderma pigmentosum: its overlap with trichothiodystrophy, Cockayne syndrome
      and other progeroid syndromes.

PMID- 19181119
TI  - Population distribution of xeroderma pigmentosum.

PMID- 19181120
TI  - Progress and prospects of xeroderma pigmentosum therapy.

PMID- 19181121
TI  - Animal models of xeroderma pigmentosum.

PMID- 19181122
TI  - Socialized medicine vs. unsocialized medicine.

PMID- 19181123
TI  - Questions about BCBS lawsuit Settlement.

PMID- 19181124
TI  - TMA's Legislative Agenda 2009: a big year for good medicine?

PMID- 19181125
TI  - Health care spending: how much is "too much"? High cost vs. low value.

PMID- 19181126
TI  - Again, it is the documentation.

PMID- 19181127
TI  - PHP: 30 years of throwing out a lifeline.

PMID- 19181128
TI  - How your medical practice can weather an economic recession.

PMID- 19181129
TI  - Respiratory failure in an 83-year-old man with multiple myeloma. Pulmonary
      alveolar proteinosis.

PMID- 19181130
TI  - Tennessee Consumer Protection Act recently extended to physicians.

PMID- 19181131
TI  - Medical liability reform: how can you help?

PMID- 19181133
TI  - An expansive view. The future of retail health clinics.

PMID- 19181134
TI  - Should you buy a franchise? A proven business model can provide framework.

PMID- 19181135
TI  - Defendant status, error disclosure.

PMID- 19181136
TI  - When your patient can't pay.

PMID- 19181137
TI  - The health benefits of dairy.

PMID- 19181138
TI  - Diagnosing sexually transmitted infection. When your patients wants to be tested
      for "everything".

PMID- 19181139
TI  - Treating allergic rhinitis in a managed care environment.

PMID- 19181140
TI  - The functional and emotional effects of migraine. Two women's stories.

PMID- 19181141
TI  - Life after bariatric surgery.

PMID- 19181142
TI  - Breath holding spells in children.

PMID- 19181143
TI  - NPs and MDs: an evolving partnership. Interview by Sarah Lebo.

PMID- 19181145
TI  - Testicular torsion.

PMID- 19181144
TI  - Life after liver transplant.

PMID- 19181146
TI  - New job, old NP. Precepting the experienced novice.

PMID- 19181147
TI  - Across the border. Learning from your neighbors to the north.

PMID- 19181148
TI  - Heredity can be a pain.

PMID- 19181150
TI  - Direct your destiny: promote yourself--and the NP profession--always.

PMID- 19181151
TI  - Differences in sexual risk management: contraceptive practices of adolescents.

PMID- 19181152
TI  - Buying a computer: a home PC won't cut it at the office.

PMID- 19181153
TI  - Itching and sores between the toes: maceration or fungal infection?

PMID- 19181154
TI  - Reducing a TMJ dislocation: a guide to passive and manual reduction.

PMID- 19181155
TI  - Patient information. Restless legs syndrome: a guide to your symptoms.

PMID- 19181156
TI  - Wound exudate: an influential factor in healing.

PMID- 19181157
TI  - Scar treatment in laser age: appropriate education and expectations are
      essential.

PMID- 19181158
TI  - Migraine in children: act now to reduce symptoms and long-term effects.

PMID- 19181159
TI  - Wound healing in older adults: unique factors should guide treatment.

PMID- 19181160
TI  - Dysfunctional uterine bleeding: close-up on a complex case.

PMID- 19181161
TI  - The road to renal failure: an overview of diabetic nephropathy.

PMID- 19181162
TI  - A double dose of risk: heart disease and metabolic syndrome in South Asians.

PMID- 19181163
TI  - When nature and pharmacy collide: drug interactions with commonly used herbs.

PMID- 19181164
TI  - Connecting to your tribe: professional peer groups.

PMID- 19181165
TI  - The teacher's teacher: memories of a mentor.

PMID- 19181166
TI  - Prognosis good for convenient care. NPs getting involved at top levels. Interview
      by Jennifer Ford.

PMID- 19181168
TI  - Creating an employee benefits package. A good selection will help retain
      employees.

PMID- 19181169
TI  - Percutaneous arterial puncture. Insertion site, positioning and technique.

PMID- 19181170
TI  - Suicide among boys and men. More challenges ahead.

PMID- 19181171
TI  - Acne in adulthood. Treat the skin and the psyche.

PMID- 19181172
TI  - Patient information. Protecting yourself against the flu. Tips for staying
      healthy.

PMID- 19181173
TI  - Coronary CT angiography. A powerful tool in the assessment of chest pain.

PMID- 19181174
TI  - Continuous oral contraception. Strategies for managing breakthrough bleeding.

PMID- 19181175
TI  - Complementary therapies for HIV.

PMID- 19181176
TI  - Oil crisis. Today's treatments for adolescent acne. Interview by Jill Rollet.

PMID- 19181177
TI  - Decompress to fight disease. Why stress requires intervention.

PMID- 19181178
TI  - Pesticide resistant head lice. Interview by Jennifer Ford.

PMID- 19181179
TI  - The ins and outs of urinary catheters. Evidence-based management.

PMID- 19181180
TI  - Danger ahead. Identifying insulin resistance.

PMID- 19181181
TI  - Get paid for your time in surgery.

PMID- 19181182
TI  - Listen to your patients.

PMID- 19181184
TI  - Isolation of epithelial cells, villi and crypts from small intestine of pigeons
      (Columba livia).
AB  - The isolation of viable enterocytes, villi and crypts from the small intestine of
      a feral bird (Columba livia) is important for performing physiological
      experiments in ecologically relevant processes of membrane transport. The
      effectiveness of mechanical disruption, enzymatic digestion and chelating agents
      were compared. The objectives were to isolate enterocytes, villi and crypts from
      the small intestine of young pigeons; to evaluate the viability of the isolated
      intestinal epithelial cells isolated; and to verify the integrity of enterocytes
      by biochemical features. Enzymatic and mechanical methods yielded both elongated
      columnar and spherical cells. With the chelating method villi and crypts were
      obtained. All methods produced a high yield of intestinal epithelial cells with
      about 50% viability. Brush border enzymes (sucrase-isomaltase and alkaline
      phosphatase) activities were high and, as reported in chickens, they did not
      differ along the intestinal villus-crypt axis. Although the three methods have
      good viabilities, the enzymatic technique gives the best yield in cell number,
      while the chelating method provides the highest populations of morphologically
      distinctive villi and crypts.

PMID- 19181183
TI  - A 66-kDa protein of bovine hypophyseal Pars tuberalis induces luteinizing hormone
      release from rat Pars distalis.
AB  - In this study, evidence for a factor secreted by bovine hypophyseal pars
      tuberalis that stimulates luteinizing hormone (LH) release from rat pars distalis
      cells is shown. The secretion products of bovine pars tuberalis cells into the
      culture medium were assayed on dispersed rat pars distalis cells in 30 min
      incubations and superfusion experiments. The culture medium from pars tuberalis
      total cell populations, added at a dose of 6 microg per tube, induced the greater
      LH release from pars distalis cells, without effect on follicle stimulating
      hormone (FSH) release. After pars tuberalis cells separation on a discontinuos
      Percoll gradient, only the culture medium of cells from 50 and 60% strength
      Percoll were able to release LH from rat pars distalis cells. Therefore, cell
      fractions from 50 and 60% strenght Percoll were cultured together. To elicit
      maximal LH release (6 times the basal output), with the addition of 2 microg of
      pars tuberalis protein was required, suggesting that these cells produce the
      factor or factors which affect pars distalis gonadotrope cells. After applying
      the pars tuberalis culture medium on 12% SDS-PAGE, the band with biological
      activity was that of 66-kDal. Fifty ng protein of its eluate released almost 9
      times the basal output of LH from pars distalis cells. Results suggest a
      modulating effect of a protein from the bovine pars tuberalis on rat cultured
      gonadotrope cells from the pars distalis.

PMID- 19181185
TI  - Isolation and molecular characterization of a cax gene from Capsella bursa
      pastoris.
AB  - A new cation exchangers (CAXs) gene was cloned and characterized from Capsella
      bursa-pastoris by rapid amplification of cDNA ends (RACE). The full-length cDNA
      sequence of cax from C. bursa-pastoris (designated as Cbcax51) was 1754 bp
      containing a 1398 bp open reading frame encoding a polypeptide of 466 amino-acid
      residues with a calculated molecular mass of 50.5 kDa and an isoelectric point of
      5.69. The predicted CbCAX51 contained an IMP dehydrogenase/GMP reductase domain,
      two Na+/Ca2+ exchanger protein domains. Comparative and bioinformatics analyses
      revealed that CbCAX51 showed extensive homology with CAX from other plant
      species. The expression analysis by different treatments indicated that Cbcax51
      could be activated by cold triggering and was related to the cold acclimation
      process, but its expression is regulated negatively by drought and not affected
      by ABA or salt.

PMID- 19181186
TI  - DNA mismatch repair gene methylation in gastric cancer in individuals from
      northern Brazil.
AB  - Gastric cancer is one of the most common malignancies. DNA methylation is
      implicated in DNA mismatch repair genes deficiency. In the present study, we
      evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and
      26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of
      gastric cancer patients from Northern Brazil. We found that none of the
      nonneoplastic samples showed methylation of any gene promoter and 50% of gastric
      cancer samples showed at least one methylated gene promoter. Methylation
      frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and
      28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were
      associated with neoplastic samples compared to nonneoplastic ones. PMS2
      methylation was associated with diffuse- and intestinal-type cancer compared with
      normal controls. Intestinal-type cancer showed significant association with MLH1
      methylation. Diffuse-type cancer was significantly associated with MSH2
      methylation. Our findings show differential gene methylation in tumoral tissue,
      which allows us to conclude that methylation is associated with gastric
      carcinogenesis. Methylation of mismatch repair genes was associated with gastric
      carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies.
      However, MSH6 does not seem to be regulated by methylation in our samples.

PMID- 19181187
TI  - Agmatine pretreatment protects retinal ganglion cells (RGC-5 cell line) from
      oxidative stress in vitro.
AB  - Agmatine, 2-(4-aminobutyl)guanidine, has been reported to have neuroprotective
      effects against various neuronal damages. In this study it was investigated
      whether agmatine pretreatment rescues the retinal ganglion cells from oxidative
      injury in vitro. After differentiation of transformed rat retinal ganglion cells
      (RGC-5 cell line) with staurosporine, agmatine (0.0 to 100.0 microM) pretreatment
      was performed for 2 hours. Subsequently, they were exposed to hydrogen peroxide
      (0.0 to 2.5 mM) as an oxidative stress. Cell viability was monitored for up to 48
      hours with the lactate dehydrogenase (LDH) assay and apoptosis was examined by
      the terminal deoxynucleotide transferase-mediated terminal uridine
      deoxynucleotidyl transferase nick end-labeling (TUNEL) method. As a result,
      differentiated RGC-5 cells were found to have decreased viability after addition
      of hydrogen peroxide in a dose-dependent manner. This hydrogen peroxide induced
      cytotoxicity caused apoptosis characterized by DNA fragmentation. Agmatine
      pretreatment not only increased cell viability but also attenuated DNA
      fragmentation. In conclusion, agmatine pretreatment demonstrated neuroprotective
      effects against oxidative stress induced by hydrogen peroxide in differentiated
      RGC-5 cells in vitro. This suggests a novel therapeutic strategy rescuing retinal
      ganglion cells from death caused by oxidative injury.

PMID- 19181188
TI  - Sequential expressions of Notch1, Jagged2 and Math1 in molar tooth germ of mouse.
AB  - The Notch signaling pathway is an evolutionary conserved mechanism that plays an
      important role in cell-cell communication and cell fate in a wide range of
      tissues. The mammalian family of Notch receptors consists of 4 members:
      Notch1/2/3/4. The Notch ligand family consists of 5 members: Delta1/3/4 and
      Jagged1/2. Math1 encodes a murine basic helix-loop-helix (bHLH) transcription
      factor that acts as positive regulator of cell differentiation. Recently, links
      between Notch and Math1 pathways were demonstrated in various tissues. Expression
      of Notch1, Jagged2 and Math1 were analyzed in the mouse molar tooth germ during
      embryonic stage (E) 13 and E15 and during postnatal stage (PN) 1, PN3, PN5, PN10
      and PN14 by using in situ hybridization. Positive Notch1 expression was found at
      the tooth bud during embryonic stages, but its expression was absent from the
      basal cells in contact with the dental mesenchyme. Jagged2 and Math1 were
      strongly expressed in differentiated ameloblasts and odontoblasts and Math1
      strong expression was even maintained until PN14 stage. Math1 showed the
      strongest expression. Our results suggest that the Notch1 signaling pathway
      through Jagged2 could be importantly related to Math1, directing the process of
      odontogenesis toward cell differentiation.

PMID- 19181190
TI  - The evolution of the primary caregiver. Computerization and interdisciplinary
      process change.

PMID- 19181189
TI  - Heme metabolism enzymes are dynamically expressed during Xenopus embryonic
      development.
AB  - As the key component of many hemoproteins (heme-containing proteins), heme is
      involved in a broad range of biological processes. Enzymes required for heme
      biosynthesis and degradation pathways are evolutionarily conserved. While heme
      metabolism has been studied extensively, the expression of heme metabolism
      enzymes during development has not been described. Here, we report that all heme
      biosynthases and two heme oxygenases, which initiate heme degradation, are
      dynamically expressed during Xenopus embryonic development. All heme synthases,
      with the exception of aminolevulinic acid synthase 2, are maternally expressed.
      At neurula stage, heme synthases are expressed in the developing neural tissue
      and in migrating neural crest cells. At the swimming tadpole stage, expression of
      heme synthases can be detected in multiple lineages, including eyes, neural crest
      cells, developing central nervous system, ventral blood island, pronephron, and
      pronephric tubule. Similar to heme synthases, heme oxygenases are expressed
      maternally. Zygotic expression of heme oxygenases is mainly restricted to the
      developing neural and neural crest lineages. Unlike heme synthases, heme
      oxygenases are not expressed in the ventral blood island and are expressed at a
      very low level in the pronephron and pronephric tubule. This indicates that heme
      metabolism may play important roles during development.

PMID- 19181191
TI  - Performance improvement--lean times ahead.

PMID- 19181192
TI  - The best IT project is not an IT project.

PMID- 19181193
TI  - Crack down. Proper HIPAA privacy controls and training could help prevent
      criminal liability for wrongful access and disclosure.

PMID- 19181194
TI  - Tower of babble. Can data standards drive healthcare interoperability?

PMID- 19181195
TI  - Medication management: more than the sum of its parts.

PMID- 19181196
TI  - Sublicensing of EHR and related systems. Licensing and contractual
      considerations.

PMID- 19181197
TI  - Process efficiency. Redesigning social networks to improve surgery patient flow.
AB  - We propose a novel approach to improve throughput of the surgery patient flow
      process of a Boston area teaching hospital. A social network analysis was
      conducted in an effort to demonstrate that process efficiency gains could be
      achieved through redesign of social network patterns at the workplace; in
      conjunction with redesign of organization structure and the implementation of
      workflow over an integrated information technology system. Key knowledge experts
      and coordinators in times of crisis were identified and a new communication
      structure more conducive to trust and knowledge sharing was suggested. The new
      communication structure is scalable without compromising on coordination required
      among key roles in the network for achieving efficiency gains.

PMID- 19181198
TI  - The missing link to success: using a business process management system to
      automate and manage process improvement.
AB  - Healthcare continues to face many significant challenges in its quest to provide
      optimal patient care. Many hospitals have instituted various process improvement
      methodologies to address these challenges. The outcome of these efforts still
      produces a large volume of manual tasks that must be addressed by the caregiver.
      The Chester County Hospital employed a Business Process Management (BPM) engine
      to automate and manage several of these processes. A BPM engine can perform key
      tasks and interact with the clinician to decrease the manual requirements of a
      process. The result is reduced workloads and improved outcomes. The Chester
      County Hospital has been able to demonstrate significant decreases in hospital
      acquired MRSA infections and compliance with several CMS core measures. There are
      multiple items to evaluate before attempting to use a BPM engine. This paper
      reviews the work at Chester County, its outcomes and the considerations that were
      important for achieving success.

PMID- 19181199
TI  - Getting 'Lean': hardwiring process excellence into Northeast Health.
AB  - Many healthcare organizations are turning to the "Lean" Toyota Production System
      as a means to hardwire process excellence into their organizations. Northeast
      Health, an integrated delivery system in New York's capital region, introduced
      the Lean concept into its culture in 2004. After four years, the organization is
      beginning to see its staff hardwire Lean thinking into day-to-day behaviors. This
      paper focuses on the approach used by Northeast Health to introduce Lean concepts
      into its culture, challenges faced, lessons learned and the factors critical to
      success.

PMID- 19181200
TI  - Clinical decision support. How CDS tools impact patient care outcomes.
AB  - Clinical decision support tools are important components of the electronic health
      record and can directly improve patient care outcomes and the performance of
      healthcare organizations. These tools can be used within order sets, electronic
      alerts, reference materials that are readily available, reports related to
      patient data, as well as clinical guidelines that were developed by regulatory
      agencies The development and use of CDS tools at the point of care offers
      clinicians the ability to analyze and work with patient data in real-time while
      making critical decisions. In the future, CDS tools will be important when
      changes in financial reimbursement related to patient care outcomes become the
      primary focus for many insurance-related organizations. This financial shift will
      have a tremendous impact on healthcare organizations bottom line. This article
      presents outcome data resulting from the implementation of several electronic CDS
      tools within a community hospital where all physicians enter orders
      electronically and clinical staff use electronic documentation.

PMID- 19181201
TI  - Improving transitional care in Hawaii: opening communication between community
      based and tertiary-care healthcare providers.
AB  - The goal of the Holomua Project is to improve transitional care between community
      health centers and tertiary care facilities through healthcare IT for, thereby
      improving care for vulnerable populations in Hawaii. Individual interviews,
      cluster interviews and roundtable discussions were conducted with healthcare
      providers in these facilities to examine transitional care processes, identify
      existing challenges and make recommendations that improve transitional care.

PMID- 19181202
TI  - The care and outcomes management plan and Kardex. A design for improving
      documentation of nursing plan of care and patient outcomes.
AB  - The gradual transition from paper records to electronic records presents
      challenges for nurses. In particular, split paper/electronic records can
      interfere with staff communication during shift change reports. A project was
      implemented to facilitate documentation of individualized care plans and improve
      staff communication during shift change report. The hospital's critical pathway
      was incorporated into Kardex to create a single electronic medical record for use
      during shift change report. This combined electronic outcomes plan and Kardex
      improved access to patient information during shift report and facilitated
      nurses' ability to update the care plan with the most current patient
      information. Future strategies will include collaboration with the hospital's
      information systems staff to make the COMPdex compatible with the hospital's
      electronic documentation system, so that pertinent patient data will populate
      from the current electronic chart into the COMPdex forms for printing and to
      include patient outcome data in the electronic medical record.

PMID- 19181203
TI  - Real option analysis--improving project selection in healthcare settings.
AB  - The effective selection of information technology projects is crucial for
      achieving gains from healthcare IT. This article introduces through example "real
      options analysis," a project selection best practice. The author discusses the
      applications of real options analysis, with emphasis on healthcare settings, and
      addresses the importance of organizational characteristics on real options
      analysis. The real options approach is an improvement over net present value
      analysis, which uses single estimates of future revenue and costs. Additionally,
      thinking of projects in terms of options helps design and manage investment
      strategies by identifying and valuing alternatives inherent in a project.

PMID- 19181204
TI  - Evaluating success. Strategies and challenges for understanding IT implementation
      in a rural hospital.
AB  - In 2004, a small rural hospital in California received a grant for the
      implementation of an integrated IT system. As part of the grant, the hospital
      worked with a university team to evaluate the implementation. The evaluation plan
      emphasized quantitative analysis of medication errors, patient safety and
      hospital finances. As the implementation progressed, it became clear that the
      quantitative methods would be marginally useful; qualitative methods gained
      greater importance. The evaluation team added more interviews and several staff
      surveys to the evaluation. The results of the surveys helped the hospital team
      understand how well staff was prepared for the technology and how they were
      responding to implementation. The best practices emphasized in this paper
      include: work with independent evaluators who can provide anonymity and lend
      objectivity; focus on surveys and interviews to understand the difficulties faced
      by staff and how they might affect outcomes; and collect key outcomes data in
      advance of beginning the implementation.

PMID- 19181205
TI  - Mesenchymal stem cell transplantation for neurodegenerative diseases.
AB  - Neurodegenerative diseases are characterized by a progressive degeneration of
      selective neural populations. The lack of effective treatment and the
      characteristic of their pathology make these diseases appropriate candidates for
      cell therapy. Mesenchymal stem cells (MSCs) are multipotent stem-like cells that
      are capable of differentiating into mesenchymal and nonmesenchymal lineages.
      Their regenerative capacity after in vivo transplantation into animal models of
      neurodegenerative diseases has suggested that they could be useful against human
      diseases. Human bone marrow-derived MSCs (hMSCs) can be easily amplified in vitro
      and their transdifferentiation has been claimed in vitro and in vivo in neural
      cells. There are some doubts concerning the exact mechanisms responsible for the
      beneficial outcome observed after MSC transplantation into neurodegenerating
      tissues. Possible interpretations include cell replacement, trophic factor
      delivery, and immunomodulation. This review mainly concerns hMSCs transplantation
      in neurodegenerative diseases, because it has proven to be feasible, safe, and
      potentially effective. Although they have been used in hundreds of clinical
      trials, mixed results and no functional and long-lasting integration have so far
      been observed. hMSCs transplantations therefore still have their "dark side."
      However, the challenge in well-planned clinical trials merits discussion.

PMID- 19181206
TI  - Long-term survival, robust neuronal differentiation, and extensive migration of
      human forebrain stem/progenitor cells transplanted to the adult rat dorsal root
      ganglion cavity.
AB  - Neurons in dorsal root ganglia (DRGs) transmit sensory information from
      peripheral tissues to the spinal cord. This pathway can be interrupted, for
      example, as the result of physical violence, traffic accidents, or complications
      during child delivery. As a consequence, the patient permanently loses sensation
      and often develops intractable neuropathic pain in the denervated area. Here we
      investigate whether human neural stem/progenitor cells (hNSPCs) transplanted to
      the DRG cavity can serve as a source for repairing lost peripheral sensory
      connections. We found that hNSPCs robustly differentiate to neurons, which
      survive long-term transplantation. The neuronal population in the transplants was
      tightly surrounded by astrocytes, suggesting their active role in neuron
      survival. Furthermore, 3 months after grafting hNSPCs were found in the dorsal
      root transitional zone (DRTZ) and within the spinal cord. The level of
      differentiation of transplanted cells was high in the core of the transplants
      whereas cells that migrated to the DRTZ and spinal cord were undifferentiated,
      nestin-expressing precursors. These data indicate that peripherally transplanted
      hNPSCs can be used for repair of dorsal root avulsion or spinal cord injuries;
      however, additional factors are required to guide their differentiation to the
      desired type of neurons. Furthermore, hNPSCs that migrate from the DRG cavity
      graft site to the DRTZ and spinal cord may provide trophic support for
      regenerating dorsal root axons, thereby allowing them to reenter the host spinal
      cord.

PMID- 19181207
TI  - Environmental housing and duration of exposure affect striatal graft morphology
      in a rodent model of Huntington's disease.
AB  - Clinical trials of cell replacement therapy in Huntington's disease have shown
      its safety, feasibility, and potentially long-lasting effects. However, more
      needs to be known regarding the conditions that stimulate plasticity and
      compensation achieved by neural grafts to maximize posttransplantation recovery
      of such neurorehabilitative therapies. The effects of enriched environment (EE),
      behavioral experience, and transplantation can each separately influence neuronal
      plasticity and recovery of function after brain damage, and the mechanisms by
      which these factors interact to modify the survival, integration, or function of
      grafted tissues are at present unknown. To investigate the effects of variable
      housing conditions and duration on morphological and cellular changes within
      embryonic striatal transplants, rats received unilateral excitotoxic lesions of
      the striatum, followed by E15 whole-ganglionic eminence suspension grafts. The
      rats were divided into three groups according to housing: full-time EE, 1 h/day
      exposure to EE, or standard laboratory cages. The experimental design included
      "early" (7 weeks postgrafting) and "late" (13 weeks postgrafting) survival time
      points to explore the effects of exposure lengths to the three housing
      conditions. The morphological and cellular effects on the grafts were analyzed
      using immunohistochemistry, cell morphology, image analysis, and enzyme-linked
      immunoassay. Both the duration of the exposure and the housing conditions were
      seen to influence multiple parameters of grafted cell morphology. The factors
      acted either independently (e.g., on graft size), complementarily (e.g., on spine
      density), or had no distinctive effect (e.g., on lesion size) on graft
      development. Features of embryonic striatal grafts and their trophic milieu were
      influenced both by the complexity of the environmental conditions and by the
      length of exposure to them. The data suggest that neurorehabilitation should be a
      feature of clinical trials of cell transplantation in order to exploit the
      underlying mechanisms that promote anatomical integration of the grafted cells
      and maximize transplant-mediated functional recovery.

PMID- 19181208
TI  - Sertoli cells enhance formation of capillary-like structures in vitro.
AB  - Sertoli cells isolated from the testis (referred to as extratesticular Sertoli
      cells) have been shown to facilitate allo- and xenogeneic cell transplantations.
      It appears likely that the ability of these cells to enhance the success of cell
      engraftment is due, in part, to the retention of their intratesticular functions
      of trophic support and immunoprotection. Sertoli cells also are involved in the
      regulation of angiogenesis in the testis, which may also contribute to enhanced
      cell engraftment success facilitated by extratesticular Sertoli cells. Because
      the maintenance of the cell's intratesticular angiogenic function has not yet
      been evaluated for extratesticular Sertoli cells, this study examined the cell's
      ability to enhance angiogenesis in vitro. Sertoli cell conditioned media were
      derived from isolated rat Sertoli cell cultures and used in a rat aortic model of
      induced angiogenesis, in endothelial and smooth muscle cell monocultures, and in
      endothelial smooth muscle cocultures. An angiogenic rat cytokine array identified
      angiogenic factors in the control and conditioned media. Aorta sections incubated
      with Sertoli cell conditioned media showed a marked increase in the formation of
      capillary-like structures when compared to controls. Likewise, endothelial cells
      incubated in conditioned media organized into capillary-like structures not
      observed when incubated in control media. In coculture, smooth muscle cells were
      associated with endothelial cell-derived capillary-like structures only when
      incubated in conditioned media. Cytokine arrays indicated the presence and a
      qualitative increase of specific angiogenic growth factors in Sertoli cell
      conditioned media not observed in control media. Results indicate that
      extratesticular Sertoli cells retain their intratesticular angiogenic function in
      vitro.

PMID- 19181209
TI  - Transplantation of mesenchymal stem cells improves atrioventricular conduction in
      a rat model of complete atrioventricular block.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells that differentiate into a
      variety of lineages including myocytes and vascular endothelial cells. However,
      little information is available regarding the therapeutic potential of MSCs in
      patients with atrioventricular block (AVB). We investigated whether local
      implantation of MSCs improves AV conduction in a rat model of complete AVB.
      Complete AVB was achieved by injection of ethanol into the AV nodal region of
      Lewis rats. Five days after ethanol injection, 2 x 10(6) of MSCs (MSC group) or
      vehicle (Control group) were injected into the AV nodal region. Animals were
      monitored by electrocardiograms for 14 days, and physiological and histological
      examinations were performed. The 1:1 AV conduction was recovered in 5 of 15 rats
      (33%) in the MSC group during the followup period, whereas no improvement was
      observed in the control group. MSC transplantation significantly decreased
      collagen deposition in the AV node, which was associated with a marked decrease
      in transforming growth factor-beta1 expression. In vitro experiments demonstrated
      that MSCs secreted a large amount of antifibrotic factors such as hepatocyte
      growth factor and interleukin-10, and MSC conditioned medium inhibited the growth
      of adult cardiac fibroblasts. In addition, local injection of MSC conditioned
      medium recovered AV conduction in 2 of 15 rats (13%). MSC transplantation
      improved AV conduction in a rat model of complete AVB, at least in part through
      antifibrotic paracrine effects.

PMID- 19181210
TI  - Mesenchymal stem cells protective effect in adriamycin model of nephropathy.
AB  - Mesenchymal stem cells (MSCs) may be of value in regeneration of renal tissue
      after damage; however, lack of biological knowledge and variability of results in
      animal models limit their utilization. We studied the effects of MSCs on
      podocytes in vitro and in vivo utilizing adriamycin (ADR) as a model of renal
      toxicity. The in vivo experimental approach was carried out in male Sprague
      Dawley rats (overall 60 animals) treated with different ADR schemes to induce
      acute and chronic nephrosis. MSCs were given a) concomitantly to ADR in tail vein
      or b) in aorta and c) in tail vein 60 days after ADR. Homing was assessed with
      PKH26-MSCs. MSCs rescued podocytes from apoptosis induced by ADR in vitro. The
      maximal effect (80% rescue) was obtained with MSCs/podocytes coculture ratio of
      1:1 for 72 h. All rats treated with ADR developed nephrosis. MSCs did not modify
      the clinical parameters (i.e., proteinuria, serum creatinine, lipids) but
      protected the kidney from severe glomerulosclerosis when given concomitantly to
      ADR. Rats given MSCs 60 days after ADR developed the same severe renal damage.
      Only a few MSCs were found in renal tubule-interstitial areas 1-24 h after
      injection and no MSCs were detected in glomeruli. MSCs reduced apoptosis of
      podocytes treated with ADR in vitro. Early and repeated MSCs infusion blunted
      glomerular damage in chronic ADR-induced nephropathy. MSCs did not modify
      proteinuria and progression to renal failure, which implies lack of regenerative
      potential in this model.

PMID- 19181211
TI  - Clonal analysis of hematopoiesis-supporting activity of human mesenchymal stem
      cells in association with Jagged1 expression and osteogenic potential.
AB  - Human mesenchymal stem cells (hMSCs) are promising feeder cells for expanding
      hematopoietic stem cells (HSCs), but their potential is heterogeneous. We
      examined the hematopoiesis-supporting activity of hMSC at the clonal level in
      relation to the osteogenic potential and gene expression. Hematopoiesis
      supporting activities of stably immortalized clonal hMSC lines were evaluated by
      the expansion of CD34+CD38- cells after 7-day coculture with human cord blood
      derived CD34+ cells. Six of 16 clones expanded the numbers of CD34+CD38- cells
      >500-fold. These hematopoiesis-supportive clones also showed high gene expression
      of Jaggedl, a Notch ligand, as well as high potential to deposit calcium after
      osteogenic induction. Thus, osteogenic hMSC clones may provide proper
      microenvironments for HSC expansion, ultimately conveying self-renewal signals to
      HSCs via the Notch pathway. However, they lost hematopoiesis-supporting activity
      after osteogenic differentiation. The hematopoiesis-supportive clones are
      potentially useful for hematopoietic microenvironment studies and as components
      of a coculture system for expansion of HSCs, free from contamination by
      xenogeneic pathogens.

PMID- 19181212
TI  - Extracellular matrix stability of primary mammalian chondrocytes and
      intervertebral disc cells cultured in alginate-based microbead hydrogels.
AB  - Three-dimensional alginate constructs are widely used as carrier systems for
      transplantable cells. In the present study, we evaluated the chondrogenic matrix
      stability of primary rat chondrocytes and intervertebral disc (IVD) cells
      cultured in three different alginate-based microbead matrices to determine the
      influence of microenvironment on the cellular and metabolic behaviors of
      chondrogenic cells confined in alginate microbeads. Cells entrapped in calcium,
      strontium, or barium ion gelled microbeads were monitored with the live/dead dual
      fluorescent cell viability assay kit and the 1,9-dimethylmethylene blue (DMB)
      assay designed to evaluate sulfated glycosaminoglycan (s-GAG) production.
      Expression of chondrogenic extracellular matrix (ECM) synthesis was further
      evaluated by semiquantitative RT-PCR of sox9, type II collagen, and aggrecan
      mRNAs. Results indicate that Ca and Sr alginate maintained significantly higher
      population of living cells compared to Ba alginate (p < 0.05). Production of s
      GAG was similarly higher in Ca and Sr alginate microbead cultures compared to Ba
      alginate microbeads. Although there was no significant difference between
      strontium and calcium up to day 14 of culture, Sr alginate showed remarkably
      improved cellular and metabolic activities on long-term cultures, with
      chondrocytes expressing as much as 31% and 44% greater s-GAG compared to calcium
      and barium constructs, respectively, while IVD cells expressed 63% and 74%
      greater s-GAG compared to calcium and barium constructs, respectively, on day 28.
      These findings indicate that Sr alginate represent a significant improvement over
      Ca- and Ba alginate microbeads for the maintenance of chondrogenic phenotype of
      primary chondrocytes and IVD cells.

PMID- 19181213
TI  - The fate of implanted syngenic muscle precursor cells in injured striated
      urethral sphincter of female rats.
AB  - We studied the outcome of syngenic skeletal muscle precursor cells (MPCs)
      implanted in the striated urethral sphincter of the female rat. These cells were
      injected at the site of a longitudinal sphincterotomy performed 21 days before
      implantation. MPCs were isolated from the striated hindlimb muscles of syngenic
      adult rats and were infected with a retrovirus carrying the gene for either the
      green fluorescent protein (GFP) or the beta-galactosidase enzyme (beta-gal). MPCs
      (2 x 10(5)) were injected longitudinally at the site of the lesion in 48 animals
      using a 10-microl Hamilton syringe. Then the whole urethras were excised from 2 h
      up to 90 days for cross section immunocytochemistry analysis. All the urethras
      exhibited connective tissue in place of the injury of the striated fibers. Two
      hours after injection a cluster of small round basophilic cells was observable at
      the site of injection and some of them expressed GFP or beta-gal. A few GFP- and
      beta-gal-positive cells were already detectable 7 days after injection. A large
      amount of injected cells probably died after injection. Many striated fibers of
      the urethra became GFP positive from day 7 until day 21, suggesting that few MPCs
      were allowed to incorporate the divided extremities of the striated fibers from
      day 7. Unfortunately, we did not observe centronucleated regenerated fibers in
      this experiment.

PMID- 19181214
TI  - Comparison of autologous full-thickness gingiva and skin substitutes for wound
      healing.
AB  - Ideally tissue-engineered products should maintain the characteristics of the
      original tissue. For example, skin represents orthokeratinized epithelium and
      oral gingiva represents parakeratinized epithelium. The aim of this study was to
      develop an autologous full-thickness gingiva substitute suitable for clinical
      applications and to compare it with our autologous full-thickness skin substitute
      that is routinely used for healing chronic wounds. Autologous full-thickness skin
      and gingiva substitutes were constructed under identical culture conditions from
      3-mm punch biopsies isolated from the upper leg or gingiva tissue, respectively.
      Both consisted of reconstructed epithelia on acellular dermis repopulated with
      fibroblasts. To compare the characteristics of the original and reconstructed
      tissue, differential morphological observations and expression of differentiation
      markers (keratins 6, 10, and 17 and stratum corneum precursors involucrin,
      loricrin, and SKALP) were determined. Skin and gingiva substitutes were
      transplanted onto therapy-resistant leg ulcers or tooth extraction sites in order
      to determine their effects on wound healing. The tissue-engineered constructs
      maintained many of the differential histological and immunohistochemical
      characteristics of the original tissues from which they were derived. The skin
      substitute was orthokeratinized, and the gingiva substitute was parakeratinized.
      Transplantation of skin (n = 19) and gingiva substitutes (n = 3) resulted in
      accelerated wound healing with no adverse effects. As identical culture systems
      were used to generate both the skin and gingiva substitutes, the differences
      observed in tissue (immuno)histology can be attributed to intrinsic properties of
      the tissues rather than to environmental factors (e.g., air or saliva). This
      study emphasizes the importance of closely matching donor sites with the area to
      be transplanted. Our results represent a large step forward in the area of
      clinical applications in oral tissue engineering, which have until now greatly
      lagged behind skin tissue engineering.

PMID- 19181215
TI  - Functional assessment of the quality of human hepatocyte preparations for cell
      transplantation.
AB  - Hepatocyte transplantation is an alternative therapy to orthotopic liver
      transplantation for the treatment of liver diseases. Good quality freshly
      isolated or cryopreserved human hepatocytes are needed for clinical
      transplantation. However, isolation, cryopreservation, and thawing processes can
      seriously impair hepatocyte viability and functionality. The aim of the present
      study was to develop a fast and sensitive procedure to estimate the quality of
      hepatocyte preparations prior to clinical cell infusion. To this end, cell
      viability, attachment efficiency, and metabolic competence (urea synthesis and
      drug-metabolizing P450 activities) were selected as objective criteria. Viability
      of hepatocyte suspension was estimated by trypan blue staining. DNA content of
      attached cells 50 min after hepatocyte platting to fibronectin/collagen-coated
      dishes was quantified to estimate adherence capacity. Urea production was
      determined after incubating hepatocyte suspensions with 2 mM C1NH4 for 30 min.
      The cytochrome P450 function was assayed by a 30-min incubation of hepatocyte
      suspension with a cocktail mixture containing selective substrates for seven
      individual P450 activities (CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4). The assay
      can be applied to both freshly isolated and cryopreserved hepatocyte suspensions,
      and the results are available within 1 h, which could help to make short-term
      decisions: 1) to assess the suitability for cell transplantation of a preparation
      of freshly isolated hepatocytes or a particular batch of thawed cells, or 2) to
      estimate the convenience of banking a particular cell preparation.

PMID- 19181216
TI  - Proliferation of hepatocyte progenitor cells isolated from adult human livers in
      serum-free medium.
AB  - Rat small hepatocytes (SHs) are committed progenitor cells that can differentiate
      into mature hepatocytes and can selectively proliferate in serum-free medium when
      they are cultured on hyaluronic acid (HA)-coated dishes. In this study we
      examined the separation of human SHs from adult human livers. We obtained liver
      tissues from the resected liver of 16 patients who underwent hepatic resections.
      Extracted liver specimens were clearly separate from the tumor regions with
      sufficient margins. Hepatic cells were isolated using the modified method of two
      step collagenase perfusion. A low-speed centrifugation was performed and cells in
      the supernatant were finally cultured on HA-coated dishes in serum-free DMEM/F12
      medium including nicotinamide, EGF, and HGF. Small-sized hepatocytes selectively
      proliferated to form colonies and many colonies continued growing for more than 3
      weeks. The average number of cells in a colony was 38.6 +/- 18.0, 79.0 +/- 54.0,
      and 101.5 +/- 115.7 at day 7, 14, and 21, respectively. About 0.04% of plated
      cells could form an SH colony. Immunocytochemistry showed that the cells forming
      a colony were positive for albumin, transferrin, keratin 8, and CD44. The results
      of RT-PCR showed that colony-forming cells expressed albumin, transferrin, alpha1
      antitrypsin, fibrinogen, glutamine synthetase, many cytochrome P450s, and liver
      enriched transcription factors (HNF3alpha, HNF4alpha, C/EBPalpha, and C/EBPbeta).
      Furthermore, the cells expressed not only the genes of hepatic differentiated
      functions but also those of both hepatic stem cell marker (Thy1.1, EpCAM, AFP)
      and SH marker (CD44, D6.1A, BRI3). Albumin secretion into culture medium was also
      observed. Our results demonstrate the existence of hepatocyte progenitor cells in
      human adult livers, and the cells can grow in a serum-free medium on HA-coated
      dishes. Human SHs may be a useful source for cell transplantation as well as
      pharmaceutical and toxicological investigations.

PMID- 19181217
TI  - A new experimental protocol for preferential differentiation of mouse embryonic
      stem cells into insulin-producing cells.
AB  - Mouse embryonic stem (ES) cells have the potential to differentiate into insulin
      producing cells, but efficient protocols for in vitro differentiation have not
      been established. Here we have developed a new optimized four-stage
      differentiation protocol and compared this with an established reference
      protocol. The new protocol minimized differentiation towards neuronal progeny,
      resulting in a population of insulin-producing cells with beta-cell
      characteristics but lacking neuronal features. The yield of glucagon and
      somatostatin cells was negligible. Crucial for this improved yield was the
      removal of a nestin selection step as well as removal of culture supplements that
      promote differentiation towards the neuronal lineage. Supplementation of the
      differentiation medium with insulin and fetal calf serum was beneficial for
      differentiation towards monohormonal insulin-positive cells. After implantation
      into diabetic mice these insulin-producing cells produced a time-dependent
      improvement of the diabetic metabolic state, in contrast to cells differentiated
      according to the reference protocol. Using a spinner culture instead of an
      adherent culture of ES cells prevented the differentiation towards insulin
      producing cells. Thus, prevention of cell attachment in a spinner culture
      represents a means to keep ES cells in an undifferentiated state and to inhibit
      differentiation. In conclusion, this study describes a new optimized four-stage
      protocol for differentiating ES cells to insulin-producing cells with minimal
      neuronal cell formation.

PMID- 19181218
TI  - Prolonged survival of microencapsulated neonatal porcine islet xenografts in
      immune-competent mice without antirejection therapy.
AB  - Several studies have demonstrated that in vitro culture of islets prolonged islet
      graft survival in immune-competent mice without administration of antirejection
      drugs. However, we recently showed that in vitro cultured microencapsulated
      neonatal porcine islets (NPI) were rejected in immune-competent mice not
      receiving antirejection therapy. The aim of this study was to determine whether
      culture of microencapsulated NPI in vivo could promote long-term survival of
      microencapsulated NPI in immune-competent mice without administration of
      antirejection drugs. Microencapsulated NPI that were cultured in vitro for 7 and
      50 days or transplanted initially in immune-deficient C.B.-17 SCID-BEIGE mice for
      100 days (in vivo cultured) were characterized and transplanted into
      streptozotocin-induced diabetic immune-competent BALB/c mice. Day 50 in vitro
      cultured and day 100 in vivo cultured microencapsulated NPI showed significantly
      higher insulin and DNA content, indicating maturation of NPI compared to day 7 in
      vitro cultured microencapsulated NPI. Interestingly, in vivo cultured
      microencapsulated NPI expressed lower levels of porcine antigens compared to day
      7 and day 50 in vitro cultured microencapsulated NPI. Transplantation of day 7 in
      vitro cultured microencapsulated NPI did not reverse diabetes in immune-competent
      BALB/c mouse recipients. In contrast, transplantation of day 50 in vitro cultured
      and in vivo cultured microencapsulated NPI into diabetic immune-competent BALB/c
      mice resulted in the immediate reversal of hyperglycemia within 2 days
      posttransplantation. However, all recipients of day 50 in vitro cultured
      microencapsulated NPI eventually rejected their grafts by day 15
      posttransplantation, while 6 of 10 BALB/c mouse recipients of in vivo cultured
      microencapsulated NPI maintained normoglycemia for 100 days posttransplantation.
      These results show that in vivo culture of NPI in immune-deficient mice results
      in the modulation of NPI, which allows for their long-term survival in immune
      competent mice without antirejection therapy.

PMID- 19181219
TI  - Cell surface modification by activated polyethylene glycol prevents
      allosensitization after islet transplantation.
AB  - The necessity to transplant islet tissue without the need for immunosuppressant
      therapy has led to the development of materials for immune modulation. Pegylation
      makes islets antigenically silent, protecting them from the adsorption of foreign
      protein and thus avoiding immune injury. The aim of this study is to determine
      whether pegylation of islets prolongs islet survival and function both during
      tissue culture and posttransplantation. We used cyanuric chloride-activated
      methoxy-polyethylene glycol for cell surface modification. To detect the
      pegylation effect on splenocytes, we measured antibody binding inhibition and
      abrogation of lymphocyte proliferation. To detect the pegylation effect on islet
      grafts, we performed rodent islet transplantation. Islet viability and function
      were maintained after pegylation. Pegylated islets showed a 90% decrease in
      antibody binding and decreased lymphocyte proliferation in a mixed lymphocyte
      culture. However, when pegylated islets were transplanted, no prolongation of
      graft survival was observed. When a subtherapeutic dose of immunosuppressant was
      given at the time of transplantation of pegylated islets, islet graft survival
      was significantly prolonged. In addition, when rats were sensitized with donor
      splenocytes, graft survival was prolonged by pegylation. We observed that
      pegylation of islets, combined with a subtherapeutic dose of immunosuppressant,
      protects the graft from rejection. Prolonged graft survival in sensitized
      recipients showed that pegylation of islets shifted the pattern of rejection from
      an acute humoral response to a less aggressive cellular alloresponse.

PMID- 19181220
TI  - Beneficial effect of the nonpeptidyl low molecular weight radical scavenger IAC
      on cultured human islet function.
AB  - We examined a possible protective effect of the nonpeptidyl low molecular weight
      radical scavenger IAC [bis(1-hydroxy-2,2,6,6-tetramethyl-4
      piperidinyl)decanedioate di-hydrochloride] on isolated human islet cells against
      isolation and culture oxidative stress. Islets isolated from pancreases of
      nondiabetic multiorgan donors by collagenase digestion were purified by density
      gradient centrifugation. After the isolation, islets were either exposed or not
      exposed for 7 days to 10 micromol/L IAC. We found that IAC markedly reduced
      oxidative stress and ameliorated islets function. These results suggest that the
      use of IAC could be an interesting pharmacological approach for the treatment of
      the islets before transplantation.

PMID- 19181221
TI  - Early outcomes of pyrolytic carbon hemiarthroplasty for the treatment of
      trapezial-metacarpal arthritis.
AB  - PURPOSE: Pyrolytic carbon implants have been successfully used in the treatment
      of osteoarthritis of the metacarpophalangeal and proximal interphalangeal joints.
      Recently, pyrolytic carbon hemiarthroplasties have been proposed for the
      treatment of osteoarthritis of the trapezial-metacarpal (TM) joint of the thumb.
      We wished to review our short-term outcomes for this device in the treatment of
      TM arthritis. METHODS: Fifty-four arthritic TM joints in 49 patients, with a mean
      age of 59 years, were treated with use of a pyrolytic carbon hemiarthroplasty
      procedure. Underlying diagnoses included osteoarthritis in 44 thumbs, rheumatoid
      arthritis in 8 thumbs, psoriatic arthritis in 1 thumb, and juvenile rheumatoid
      arthritis in 1 thumb. The patients were followed up clinically as well as
      radiologically for an average of 22 months postoperatively. RESULTS: The overall
      22-month survival rate excluding scaphotrapezio-trapezoidal joint arthritis was
      80% according to a Kaplan-Meier analysis. Ten metacarpal subluxations were
      observed. Seven of these cases were salvaged by increasing the depth of the
      trapezial cup. A total of 15 reoperations were required in this cohort. No
      complications were seen in the patients with inflammatory arthritis. Thirty-five
      patients were pain free at the latest follow-up, and 6 reported mild to
      occasional pain with repetitive activities. The overall satisfaction rate was 40
      of 49 patients (81%). Grip strength recovered to 86% of that of the contralateral
      side. Apposition key and opposition pinch strength improved to 92% and 95%,
      respectively, of those of the contralateral hand. CONCLUSIONS: Pyrolytic carbon
      thumb arthroplasty may prove to be an acceptable option for the treatment of TM,
      although a high complication rate was observed in this early cohort, with many
      cases of subluxation attributed to the creation of a too shallow trapezial cup.
      Further comparative studies are warranted. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 19181222
TI  - Trapeziectomy and carpal collapse.
AB  - PURPOSE: Trapeziectomy for the treatment of trapeziometacarpal (TM)
      osteoarthritis (OA) disrupts the scaphotrapezium-trapezoidal ligament complex and
      may be associated with carpal collapse in a subset of patients in the form of
      nondissociative dorsal intercalated segment instability (DISI). The purpose of
      this study was to examine the clinical and radiographic outcomes of
      trapeziectomy, documenting the incidence of postoperative carpal collapse, and to
      determine whether this outcome is correlated with preoperative radiographic
      findings. METHODS: A retrospective chart and radiographic review was performed on
      33 wrists having trapeziectomy from January 1999 to January 2006. Three surveys
      were administered to patients after surgery to assess subjective levels of pain,
      function, and satisfaction. The Wilcoxon signed-rank test was used to determine
      significant differences in radiographic angles, and McNemar's chi-square test was
      used to determine significant differences in the frequency of a DISI finding.
      RESULTS: Stage IV disease was present in 58% of wrists; all wrists were followed
      up at a mean of 10.5 months after surgery. The mean postoperative change in the
      radiolunate angle was 4.4 degrees of increased dorsal tilt. Radioscaphoid angles
      changed after surgery by a mean of 6.3 degrees of increased extension. The
      frequency of DISI as measured by the radiolunate angle increased significantly,
      from 27% before surgery to 50% after surgery. Scaphotrapezium-trapezoidal
      arthritis was observed in 58% of wrists; within this subset, DISI was present in
      39% before surgery and 62% after surgery. Those patients with a DISI deformity
      were significantly less satisfied following surgery than those without this
      finding. CONCLUSIONS: Patients having trapeziectomy for treatment of TM OA may be
      at risk for the development of carpal instability. This instability may manifest
      through either a DISI posture of the wrist or abnormal extension of the scaphoid
      in the presence of a normal scapholunate angle. The presence of stage IV TM OA
      may be correlated with an increased incidence of carpal instability after
      surgical intervention. These radiographic findings are mirrored by a trend toward
      increased levels of pain and decreased levels of function and satisfaction in
      those patients with evidence of DISI. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 19181223
TI  - Percutaneous screw fixation for scaphoid fracture: a comparison between the
      dorsal and the volar approaches.
AB  - PURPOSE: To evaluate the position of the screws and find the difference of
      clinical and radiologic outcome between the volar approach and the dorsal
      approach groups in percutaneous screw fixation for acute scaphoid fractures.
      METHODS: Forty-one consecutive patients with an acute scaphoid fracture, who had
      percutaneous fixation via either the volar approach or the dorsal approach, were
      evaluated at an average of 30 months after the surgery. The volar approach was
      used in 19 patients and the dorsal approach in 22 patients. By using a
      computerized digital image program, angles between the Herbert screw with respect
      to the long axis of the scaphoid and the fracture line were measured with plain
      radiographs in the posteroanterior, lateral, and the 45 degrees semipronated
      oblique views. RESULTS: The screws showed no significant difference between the 2
      groups in posteroanterior and lateral views; however, screws in the dorsal
      approach group were observed to be placed more parallel to the long axis of the
      scaphoid in the semipronated oblique view. The screws in the dorsal approach
      group were positioned more perpendicular to the fracture lines of the scaphoid
      compared with those of the volar approach group for all 3 different radiographic
      views. There was no statistically significant difference between the 2 treatment
      groups regarding fracture healing. According to the Mayo wrist score system,
      excellent results were recorded in 18 patients in the dorsal approach group and
      15 patients in the volar approach group. CONCLUSIONS: This study suggests that
      screws are placed more parallel to the long axis of the scaphoid and
      perpendicular to the fracture line via the dorsal approach; however, there was no
      significant difference with regard to functional outcome and bone union. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 19181224
TI  - Dorsal radiocarpal ligament capsulodesis for chronic dynamic lunotriquetral
      instability.
AB  - PURPOSE: Chronic lunotriquetral (LT) instability (persisting >3 months after
      injury) can be treated with a variety of surgical methods (LT fusion, ligament
      repair or reconstruction, or arthroscopic debridement), with varying degrees of
      success. We retrospectively evaluated the results of dorsal capsulodesis using
      the dorsal radiocarpal ligament in an attempt to reinforce the dorsal LT
      interosseous ligament in patients with chronic dynamic LT instability. METHODS: A
      total of 11 patients (mean age, 37 years) with persistent posttraumatic wrist
      pain and weakness were diagnosed with dynamic LT instability (positive LT
      ballotment test, disruption of Gilula's lines or volar intercalated segment
      instability deformity on stress radiography, arthroscopic findings of Geissler
      grade 3, or 4 LT tears). They were treated consecutively with dorsal
      capsulodesis. We used subjective and functional outcome measures to evaluate the
      results. RESULTS: The mean follow-up period was 31 months (range, 12-65 months).
      The postoperative visual analog pain score and Mayo wrist score were
      significantly improved compared with their preoperative values. The average grip
      strength increased by 5 kg, and the average range of wrist flexion was reduced by
      3 degrees . CONCLUSIONS: In this small series, in the short term, dorsal
      radiocarpal ligament capsulodesis reduced pain and instability and improved
      function in patients with chronic dynamic LT instability. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 19181225
TI  - Proximal row carpectomy: role of a radiocarpal interposition lateral meniscal
      allograft.
AB  - PURPOSE: The purpose of this study was to determine whether use of a lateral
      meniscal interposition allograft combined with proximal row carpectomy would
      reduce the peak joint contact pressures and increase the contact area when
      compared with proximal row carpectomy alone. METHODS: Six cadaver wrists were
      cyclically moved through flexion-extension and radioulnar deviation ranges of
      motion. Joint contact pressure was measured with the carpus intact, after
      proximal row carpectomy, and after insertion of a lateral meniscal allograft.
      Contact pressure data were also collected with the wrist in 5 static positions.
      RESULTS: Proximal row carpectomy caused statistically greater peak pressures and
      smaller contact areas when compared with the intact wrist. Insertion of the
      allograft statistically restored the pressures and areas to that observed in the
      intact wrist. CONCLUSIONS: These results support the clinical trial of a lateral
      meniscal interposition allograft in patients with contraindications for proximal
      row carpectomy, such as pre-existing arthritis in the capitate head or lunate
      facet of the radius.

PMID- 19181226
TI  - Open compared with 2-portal endoscopic carpal tunnel release: a 5-year follow-up
      of a randomized controlled trial.
AB  - PURPOSE: The purpose of this investigation was to extend the previously reported
      short-term randomized trial of open and endoscopic carpal tunnel release in
      patients with carpal tunnel syndrome (CTS) to compare outcomes 5 years after
      surgery. METHODS: In a single-center randomized controlled trial, 128 patients
      (25 to 60 years) with clinically diagnosed and electrophysiologically confirmed
      idiopathic CTS were randomized immediately before surgery to open or 2-portal
      endoscopic release. The outcome measures included the validated CTS
      questionnaire's symptom severity and functional status scales (scored from 1 to
      5) completed at baseline and 1 year postoperatively. At the extended follow-up of
      the trial 5 years after surgery, 2 patients had died and the other 126
      participants (63 patients in each group) completed the CTS questionnaire.
      RESULTS: At the 5-year follow-up no difference between the groups was found in
      the CTS symptom severity score. The mean (SD) score in the open group was 1.42
      (0.7) and in the endoscopic group was 1.45 (0.7), and the mean difference in
      score change from baseline was 0.03 (95% confidence interval, -0.21 to 0.27).
      Between 1 year and 5 years postoperatively, the CTS symptom severity score had
      deteriorated by at least 0.4 point in 9 patients in the open group and in 10
      patients in the endoscopic group. The mean (SD) CTS functional status score was
      1.29 (0.5) in the open group and 1.30 (0.5) in the endoscopic group. At 5 years,
      11 patients in the open group and 10 patients in the endoscopic group reported
      persistent pain in the scar or proximal palm. Three patients in each group had
      repeat surgery on the operated hand because of persistent or recurrent symptoms.
      CONCLUSIONS: The improvements in symptoms of CTS and hand-related disability 5
      years after open and 2-portal endoscopic carpal tunnel release were equivalent.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

PMID- 19181227
TI  - Comparative responsiveness of the Michigan Hand Outcomes Questionnaire and the
      Carpal Tunnel Questionnaire after carpal tunnel release.
AB  - PURPOSE: The literature supports self-administered questionnaire assessment tools
      for the measurement of outcome after surgical treatment of carpal tunnel syndrome
      (CTS). Traditional physical measures are less sensitive to clinical changes
      following carpal tunnel release (CTR) than fully validated designed outcome
      questionnaires. A number of validated outcome instruments have been compared to
      determine which is optimal with regard to sensitivity and responsiveness
      following surgery. To our knowledge, the Michigan Hand Outcomes Questionnaire
      (MHQ) and the Carpal Tunnel Questionnaire (CTQ) have not been compared in regard
      to their responsiveness and sensitivity to change following CTR. The aim of this
      prospective study was to compare the responsiveness of these 2 instruments when
      evaluating outcomes after CTR. METHODS: Seventy-eight patients diagnosed with CTS
      and scheduled for unilateral open CTR were recruited and informed consent was
      obtained after ethics approval. Inclusion criteria were primary procedure,
      history, clinical signs, and conduction studies consistent with CTS. The MHQ and
      CTQ were both completed by each patient preoperatively and 6 months
      postoperatively. RESULTS: Results for all domains of the MHQ and all domains of
      the CTQ showed significant postoperative improvement. The overall responsiveness
      of both MHQ and CTQ were large (standardized response mean >or=0.8), however the
      CTQ demonstrated increased sensitivity to change after CTR compared to the MHQ.
      Although the standardized response mean (SRM) of the MHQ was 0.8, the SRM of the
      CTQ was 1.22. Both domains of the CTQ had an SRM well above 0.8, whereas half of
      the MHQ domains had an SRM below 0.8. CONCLUSIONS: The CTQ has demonstrated a
      greater responsiveness to clinical change following CTR than the MHQ. Therefore,
      the CTQ is a more sensitive instrument and researchers in the field of CTS should
      bear these findings in mind when choosing an outcome instrument for future
      studies. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic I.

PMID- 19181228
TI  - Patient-reported outcome after peripheral nerve injury.
AB  - PURPOSE: This study evaluated patient-reported outcome and the factors associated
      with disability after an upper extremity nerve injury. We hypothesized that
      patients at least 6 months after injury would report considerable disability and
      that pain would be the strongest predictor of the Disabilities of the Arm,
      Shoulder, and Hand (DASH) score. METHODS: After research ethics board approval,
      the medical charts of patients with these inclusion criteria were reviewed:
      adults; presenting to a nerve surgeon; 6 months or greater after nerve injury.
      Patients completed the DASH questionnaire and the Short Form-36 (SF-36) as a
      routine part of the initial evaluation. These data were reviewed retrospectively
      to determine predictors of the DASH score. RESULTS: There were 84 patients (mean
      age, 39 years; SD, 14 years) with brachial plexus (n=27) and peripheral nerve
      (n=57) injuries. The mean time after injury was 38 months (SD, 47). For all SF-36
      domains, the mean values of the nerve-injured patients were significantly lower
      than the normative data, indicating a lower health status. The mean DASH score
      was 52 (SD, 22) of 100. Significantly more disability was associated with more SF
      36 bodily pain and with brachial plexus injuries. In the final regression model,
      SF-36 bodily pain, age, and nerve injured were significant predictors of the DASH
      score. SF-36 bodily pain accounted for 35% of the variance. CONCLUSIONS:
      Substantial long-term disability (high DASH scores) was found in patients after
      nerve injury that was predicted by higher pain, older age, and brachial plexus
      injury. Further investigation of this pain and the associated factors may provide
      the opportunity for improved health-related quality of life. TYPE OF STUDY/LEVEL
      OF EVIDENCE: Prognostic II.

PMID- 19181229
TI  - Anterior interosseous nerve palsy after open capsular release for elbow
      stiffness: report of 2 cases.
AB  - Surgical release of elbow contracture has been associated with injury to
      structures traversing the elbow. Injury to ulnar and radial nerves has been
      reported, but this review describes 2 cases of anterior interosseous nerve palsy
      after open release of an established elbow contracture.

PMID- 19181230
TI  - Anatomically neutral silicone small joint arthroplasty for osteoarthritis.
AB  - PURPOSE: Surgical treatment of osteoarthritis at the metacarpophalangeal (MCP)
      and proximal interphalangeal (PIP) joints includes arthrodesis and, more
      recently, arthroplasty. Silicone joint arthroplasty has been shown to relieve
      pain and restore function in damaged joints. The purpose of this study was to
      assess outcomes in patients who had MCP or PIP arthroplasty for osteoarthritis
      using the NeuFlex implant (DePuy, Warsaw, IN), a silicone implant with an
      anatomically neutral design. METHODS: A total of 13 MCP and 16 PIP joint
      replacements in 19 patients were performed with a mean follow-up period of 4
      years (range, 1-8 years). Failed conservative management of osteoarthritis was
      the indication for surgery in all cases. There were 10 men and 9 women. The
      average age at the time of surgery was 66 years. Outcomes were assessed by
      questionnaire evaluation, physical examination, and radiographs. RESULTS: The
      mean flexion arc of motion was 65 degrees and 61 degrees , and the mean extension
      lag was 3 degrees and 0 degrees in the MCP and PIP groups, respectively. Pain
      relief was rated excellent or good in 84 percent. The overall patient
      satisfaction was 90 percent. The Michigan Hand Outcomes Questionnaire (MHQ) score
      at follow-up was 88 in the MCP group and 87 in the PIP group. There was 1 implant
      fracture in the PIP group. CONCLUSIONS: At mean 4-year follow-up evaluation, we
      report high rates of pain relief and patient satisfaction, a low rate of implant
      fracture, and highly satisfactory range of motion values compared to other
      implant designs. We show that treatment of MCP and PIP osteoarthritis with an
      anatomically neutral implant can provide reliable, long-term pain relief and
      maintenance of function. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 19181231
TI  - Recurrent synovial chondromatosis of the distal interphalangeal joint: case
      report.
AB  - A 59-year-old woman presented with recurrent synovial chondromatosis of the
      distal interphalangeal joint at the site of removal of what was thought to be a
      ganglion cyst in 2003 and the subsequent excision of a recurrent synovial
      chondromatosis in 2005. Although synovial chondromatosis is typically described
      as a benign, self-limiting process, recurrent disease and local erosion of the
      joint of this patient required wide excision with bone grafting and arthrodesis
      for definitive treatment.

PMID- 19181232
TI  - Bone-periosteum-bone graft reconstruction for chronic ulnar instability of the
      metacarpophalangeal joint of the thumb--minimum 5-year follow-up evaluation.
AB  - PURPOSE: The present study evaluated prospectively the functional and
      radiological results of a consecutive series of 7 patients who had bone
      periosteum-bone (BPB) grafts harvested from the iliac crest for treatment of
      chronic ulnar instability of the metacarpophalangeal (MCP) joint of the thumb
      after a minimum of 60 months. METHODS: Seven thumbs from 7 patients were entered
      into a prospective study for surgical treatment of chronic finger joint
      instability. Treatment consisted of reconstruction of the ulnar collateral
      ligament of the MCP joint of the thumb by a BPB graft harvested from the iliac
      crest. Stability, range of motion, pinch grip, and radiographs were evaluated at
      least 60 months after surgery. RESULTS: All 7 patients had full active range of
      motion of the treated thumb at the final follow-up evaluation (average, 75 months
      after surgery). All patients had equal stability and normal pinch grip when
      comparing with the untreated thumb. The mean time off work was 3 months for 6
      patients who were injured at work. At final follow-up evaluation, radiographs
      showed all grafts incorporated without implant complications, no osteoarthritis
      changes were noted, and stress radiographs showed that all patients had normal
      stability in the treated thumb when compared with the untreated thumb.
      CONCLUSIONS: Chronic ulnar instability of the MCP joint of the thumb
      reconstructed with BPB graft harvested from the iliac crest is an effective and
      safe method to allow restoration and maintenance of a stable, pain-free thumb.
      The results of the current study support the long-term durability of this method.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 19181233
TI  - Quantified contours of curvature in female index, middle, ring, and small
      metacarpophalangeal joints.
AB  - PURPOSE: To study and quantify the morphology of the curvature of the surfaces of
      metacarpophalangeal metacarpophalangeal joints and to relate joint morphology to
      joint function. METHODS: Forty metacarpophalangeal joints of the index, middle,
      ring, and small fingers from 5 right and 5 left hands were taken from female
      cadavers. The articulating surfaces of the metacarpal head and the base of the
      proximal phalanx were copied in a true-to-scale fashion. The hard plaster models
      were sliced in 7 sagittal and 7 transverse planes. The curvatures of the section
      contours were determined with circular gauges. Statistical analyses were
      performed by analysis of variance and paired Student t-tests. RESULTS: In the
      sagittal plane, the cartilaginous surface of the metacarpal head is divided into
      2 functional regions and a third dorsal region that does not articulate with the
      base of the proximal phalanx. The articulating surface of the base of the
      proximal phalanx approximates a circle in the midsagittal plane. The mean median
      sagittal radius of curvature of the dorsal articulating aspect of the metacarpal
      head (6.9 mm) is 33% smaller than that of the base of the proximal phalanx (10.3
      mm). The palmar articulating aspect of the metacarpal head (5.8 mm) is 44%
      smaller than that of the base of the proximal phalanx (10.3 mm). In the median
      transverse section, the mean radius of curvature of the metacarpal head (7.3 mm)
      is 18% smaller than that of the base of the proximal phalanx (8.9 mm).
      CONCLUSIONS: The data demonstrate the highly significant incongruity in the
      curvature of the articulating pair. This incongruity provides a joint space with
      its greatest dimension in the sagittal plane. From a mechanical perspective, the
      metacarpophalangeal joint mechanically represents a joint with 5 kinematic
      degrees of freedom: 2 for flexion and extension, 2 for abduction and adduction,
      and 1 for axial rotation.

PMID- 19181234
TI  - Management of advanced trapeziometacarpal arthrosis.

PMID- 19181235
TI  - Modified step-cut osteotomy for metacarpal and phalangeal rotational deformity.
AB  - PURPOSE: Rotational deformity of metacarpal and phalangeal fractures can
      jeopardize normal hand function and cause aesthetic problems for patients. We
      have found the Z-cut metacarpal osteotomy, initially described by Manktelow, to
      prove predictable and provide precise restoration of rotation and function.
      Therefore, we reviewed our experience with this technique. METHODS: The senior
      authors identified 12 patients treated with rotational step-cut osteotomies for
      digital rotatory deformities. The cases were reviewed retrospectively. Seven had
      metacarpal and five had phalangeal malunions. RESULTS: All 12 patients had
      correction of their deformities, obtained union of the osteotomy, and maintained
      or improved their motion. There were no perioperative complications. CONCLUSIONS:
      Metacarpal step-cut osteotomies are a technically simple and effective method for
      correction of digital rotational deformities resulting from fracture malunions.
      Unlike other types of osteotomies, this technique affords precise intraoperative
      control at the osteotomy site, a large surface area for bony healing, and rigid
      fixation with early digital motion.

PMID- 19181236
TI  - Intramedullary fixation of distal radius fractures.
AB  - Intramedullary fixation has recently received increased enthusiasm as an option
      for distal radius fracture fixation. Indications for this fracture fixation
      technique should be limited to predominately displaced extra-articular or simple
      intra-articular distal radius fractures. Intramedullary fixation permits limited
      soft tissue dissection and insertion of a low-profile implant that acts as an
      internal splint. Purported benefits include a familiar fracture fixation
      technique, less soft tissue irritation, and locked fixed-angle technology.
      Thorough understanding of the radial and dorsal approaches to the distal radius
      is a prerequisite. Important aspects of intramedullary fixation of distal radius
      fractures include proper fracture selection, good fracture reduction, protection
      of sensory nerves, and avoidance of inadvertent intra-articular screw placement.
      Relevant surgical anatomy, technique, postoperative care, and a review of
      complications are presented.

PMID- 19181237
TI  - Disease-modifying antirheumatic drugs.

PMID- 19181238
TI  - Reconstruction of the distal ulna: instability, impaction, impingement, and
      arthrosis.
AB  - A number of afflictions may affect the distal radioulnar joint that can lead to
      severe pain, disuse, dysfunction, and disability. The disorders that affect this
      small anatomic region are complex, have multifactorial etiologies, and can
      sometimes present difficult diagnostic and treatment options. This article
      presents an overview of recent developments in the diagnosis and treatment of a
      variety of conditions that affect the joint and surrounding bone and soft
      tissues.

PMID- 19181239
TI  - Proximal ulna fractures.
AB  - Proximal ulna fractures are relatively common. They range in severity from a
      simple transverse olecranon fracture to a highly complex fracture dislocation
      involving a comminuted coronoid process. The anatomy, fracture pathology,
      treatment approach, and rehabilitation are presented in this article.

PMID- 19181240
TI  - Stability of locking screws.

PMID- 19181242
TI  - Use of pegs in volar locking plates.

PMID- 19181243
TI  - Percent plate contact measurement.

PMID- 19181247
TI  - More Pisces and fellow signs in the aquarium, greater distortions? Predictors of
      inflation in type I error.

PMID- 19181248
TI  - Dosimetric comparison between 3DCRT and IMRT using different multileaf
      collimators in the treatment of brain tumors.
AB  - We investigated the differences between 3-dimensional conformal radiotherapy
      (3DCRT) and intensity modulated radiotherapy (IMRT), and the impact of collimator
      leaf-width on IMRT plans for the treatment of nonspherical brain tumors. Eight
      patients treated by 3DCRT with Novalis were selected. We developed 3 IMRT plans
      with different multileaf collimators (Novalis m3, Varian MLC-120, and Varian MLC
      80) with the same treatment margins, number of beams, and gantry positions as in
      the 3DCRT treatment plans. Treatment planning utilized the BrainLAB treatment
      planning system. For each patient, the dose constraints and optimization
      parameters remained identical for all plans. The heterogeneity index, the
      percentage target coverage, critical structures, and normal tissue volumes
      receiving 50% of the prescription dose were calculated to compare the dosimetric
      difference. Equivalent uniform dose (EUD) and tumor control probability (TCP)
      were also introduced to evaluate the radiobiological effect for different plans.
      We found that IMRT significantly improved the target dose homogeneity compared to
      the 3DCRT. However, IMRT showed the same radiobiological effect as 3DCRT. For the
      brain tumors adjacent to (or partially overlapping with) critical structures,
      IMRT dramatically spared the volume of the critical structures to be irradiated.
      In IMRT plans, the smaller collimator leaf width could reduce the volume of
      critical structures irradiated to the 50% level for those partially overlapping
      with the brain tumors. For relatively large and spherical brain tumors, the
      smaller collimator leaf widths give no significant benefit.

PMID- 19181249
TI  - Technical and dosimetric considerations in multi-isocenter intensity modulated
      radiotherapy for nasopharyngeal carcinoma with small multileaf collimator.
AB  - Multileaf collimator (MLC)-assisted intensity modulated radiotherapy (IMRT) has
      greatly improved the target coverage and avoidance of organs at risk (OAR) for
      the treatment of nasopharyngeal carcinoma; however, its implementation is also
      constrained by the features of the MLC. Nasopharyngeal carcinoma tends to have a
      large gross target volume (GTV) and clinical target volume (CTV) due to its
      biological characteristics. More than one isocenter may be needed when small MLCs
      (i.e., BrainLAB M3, whose largest field is 10 x 10 cm(2)) are used to treat the
      nasopharyngeal carcinoma. The BrainLAB IMRT system was used to evaluate the
      effectiveness of a multi-isocenter IMRT plan for treating nasopharyngeal cancers.
      Dose coverage of GTVs and CTVs were compared among IMRT plans with 1, 2 and 3
      isocenters, as were dose objectives for OARs including brainstem, cord, and
      parotids. The dosimetric variation and the delivery time were also measured with
      a phantom. IMRT plans with more than 1 isocenter achieved a better dose coverage,
      homogeneity, and conformity on GTVs and CTVs; however, with risk of higher doses
      given to OARs. In most cases, one can generate satisfactory IMRT plans using the
      2-isocenter IMRT planning strategy. Two-isocenter planning strategy may be a
      suitable compromise when more isocenters are needed.

PMID- 19181250
TI  - A technique for verification of isocenter position in tangential field breast
      irradiation.
AB  - Treatment verification and reproducibility of the breast treatment portals play a
      very important role in breast radiotherapy. We propose a simple technique to
      verify the planned isocenter position during treatment using an electronic portal
      imaging device. Ten patients were recruited in this study and (CT) computed
      tomography-based planning was performed with a conventional tangential field
      technique. For verification purposes, in addition to the standard medial (F1) and
      lateral (F2) tangential fields, a field (F3) perpendicular to the medial field
      was used for verification of the treatment portals. Lead markers were placed
      along the central axis of the 2 defined fields (F1 and F3) and the separation
      between the markers was measured on the portal images and verified with the
      marker separation on the digitally reconstructed radiographs (DRRs). Any
      deviation will identify the shift in the planned isocenter position during
      treatment. The average deviation observed between the markers measured from the
      DRR and portal image was 1.6 and 2.1 mm, with a standard deviation of 0.4 and 0.9
      mm for fields F1 and F3, respectively. The maximum deviation observed was 3.0 mm
      for field F3. This technique will be very useful in patient setup for tangential
      breast radiotherapy.

PMID- 19181251
TI  - Optimized dose distribution of Gammamed plus vaginal cylinders.
AB  - Endometrial carcinoma is the most common malignancy arising in the female genital
      tract. Intracavitary vaginal cuff irradiation may be given alone or with external
      beam irradiation in patients determined to be at risk for locoregional
      recurrence. Vaginal cylinders are often used to deliver a brachytherapy dose to
      the vaginal apex and upper vagina or the entire vaginal surface in the management
      of postoperative endometrial cancer or cervical cancer. The dose distributions of
      HDR vaginal cylinders must be evaluated carefully, so that clinical experiences
      with LDR techniques can be used in guiding optimal use of HDR techniques. The aim
      of this study was to optimize dose distribution for Gammamed plus vaginal
      cylinders. Placement of dose optimization points was evaluated for its effect on
      optimized dose distributions. Two different dose optimization point models were
      used in this study, namely non-apex (dose optimization points only on periphery
      of cylinder) and apex (dose optimization points on periphery and along the
      curvature including the apex points). Thirteen dwell positions were used for the
      HDR dosimetry to obtain a 6-cm active length. Thus 13 optimization points were
      available at the periphery of the cylinder. The coordinates of the points along
      the curvature depended on the cylinder diameters and were chosen for each
      cylinder so that four points were distributed evenly in the curvature portion of
      the cylinder. Diameter of vaginal cylinders varied from 2.0 to 4.0 cm. Iterative
      optimization routine was utilized for all optimizations. The effects of various
      optimization routines (iterative, geometric, equal times) was studied for the 3.0
      cm diameter vaginal cylinder. The effect of source travel step size on the
      optimized dose distributions for vaginal cylinders was also evaluated. All
      optimizations in this study were carried for dose of 6 Gy at dose optimization
      points. For both non-apex and apex models of vaginal cylinders, doses for apex
      point and three dome points were higher for the apex model compared with the non
      apex model. Mean doses to the optimization points for both the cylinder models
      and all the cylinder diameters were 6 Gy, matching with the prescription dose of
      6 Gy. Iterative optimization routine resulted in the highest dose to apex point
      and dome points. The mean dose for optimization point was 6.01 Gy for iterative
      optimization and was much higher than 5.74 Gy for geometric and equal times
      routines. Step size of 1 cm gave the highest dose to the apex point. This step
      size was superior in terms of mean dose to optimization points. Selection of dose
      optimization points for the derivation of optimized dose distributions for
      vaginal cylinders affects the dose distributions.

PMID- 19181252
TI  - In vivo diode dosimetry for IMRT treatments generated by Pinnacle treatment
      planning system.
AB  - Dose verification using diodes has been proposed and used for intensity modulated
      radiation therapy (IMRT) treatments. We have previously evaluated diode response
      for IMRT deliveries planned with the Eclipse/Helios treatment planning system.
      The Pinnacle treatment planning system generates plans that are delivered in a
      different fashion than Eclipse. Whereas the Eclipse-generated segments are
      delivered in organized progression from one side of each field to the other,
      Pinnacle-generated segments are delivered in a much more randomized fashion to
      different areas within the field. This makes diode measurements at a point more
      challenging because the diode may be exposed fully or partially to multiple small
      segments during one single field's treatment as opposed to being exposed to very
      few segments scanning across the diode during an Eclipse-generated delivery. We
      have evaluated in vivo dosimetry for Pinnacle-generated IMRT plans and
      characterized the response of the diode to various size segments on phantom. We
      present results of patient measurements on approximately 300 fields, which show
      that 76% of measurements agree to within 10% of the treatment-plan generated
      calculated doses. Of the other 24%, about 11% are within 15% of the calculated
      dose. Comparison of these with phantom measurements indicates that many of the
      discrepancies are due to diode positioning on patients and increased diode
      response at short source-to-surface distances (SSDs), with the remainder
      attributable to other factors such as segment size and partial irradiation of the
      diode.

PMID- 19181253
TI  - Variability of gross tumor volume delineation in head-and-neck cancer using
      PET/CT fusion, Part II: the impact of a contouring protocol.
AB  - The purpose of this study was to assess the efficacy of a gross tumor volume
      (GTV) contouring protocol on interobserver variability between 4 physicians in
      positron emission therapy/computed tomography (PET/CT) treatment planning of head
      and-neck cancer. A GTV contouring protocol for PET/CT treatment planning was
      developed utilizing 4 stages: Preliminary contouring on CT alone, determination
      of appropriate PET windowing, accurate image registration, and modification of CT
      contouring with correctly formatted PET/CT display and rules for modality
      disagreement. Two neuroradiologists and 2 radiation oncologists (designated as A,
      B, C, and D, respectively) were given a tutorial of PET/CT coregistered imaging
      individualized to their skill level, which included a step-by-step explanation of
      the protocol with clinical examples. Opportunities for questions and hands-on
      practice were given. The physicians were asked to re-contour 16 head-and-neck
      patients from Part I on PET/CT fusion imaging. Differences in volume magnitude
      were analyzed for statistical significance by analysis of variance (ANOVA) and
      paired t-tests (alpha<0.05). Volume overlap was analyzed for statistical
      significance using Wilcoxon signed-rank tests (alpha<0.05). Volume overlap
      increased significantly from Part I to Part II (p<0.05). One previously
      significant difference between physicians disappeared with the protocol in place.
      The mean fusion volume of Physician C, however, remained significantly larger
      than that of Physician D (p<0.01). This result is unchanged from Part I. The
      multidisciplinary contouring protocol significantly improved the coincidence of
      GTVs contoured by multiple physicians. The magnitudes of the volumes showed
      marginal improvement in consistency. Developing an institutional contouring
      protocol for PET/CT treatment planning is highly recommended to reduce
      interobserver variability.

PMID- 19181254
TI  - Impact of different CT slice thickness on clinical target volume for 3D conformal
      radiation therapy.
AB  - The purpose of this study was to present the variation of clinical target volume
      (CTV) with different computed tomography (CT) slice thicknesses and the impact of
      CT slice thickness on 3-dimensional (3D) conformal radiotherapy treatment
      planning. Fifty patients with brain tumors were selected and CT scans with 2.5-,
      5-, and 10-mm slice thicknesses were performed with non-ionic contrast
      enhancement. The patients were selected with tumor volume ranging from 2.54 cc to
      222 cc. Three-dimensional treatment planning was performed for all three CT
      datasets. The target coverage and the isocenter shift between the treatment plans
      for different slice thickness were correlated with the tumor volume. An important
      observation from our study revealed that for volume <25 cc, most of the cases
      were underdosed by 18% with 5-mm slice thickness and 27% with 10-mm slickness.
      For volume >25 cc, the target underdosage was less than 6.7% for 5-mm slice
      thickness and 8% for 10-mm slice thickness. For 3D conformal radiotherapy
      treatment planning (3DCRT), a CT slice thickness of 2.5 mm is optimum for tumor
      volume <25 cc, and 5 mm is optimum for tumor volume >25 cc.

PMID- 19181255
TI  - Comparison of various radiation therapy techniques in breast cancer where target
      volume includes mammaria interna region.
AB  - In breast cancer radiotherapy, the internal mammary lymphatic chain is treated in
      the target volume in a group of patients with high-risk criteria. Because of the
      variability of the anatomic region and structures in the irradiation field, there
      are a number of different techniques in breast radiotherapy. While irradiating
      the target volume, we also consider minimizing the dose to critical structures
      such as heart, lung, and contralateral breast tissue. In this study, we evaluated
      the dose distribution of different radiotherapy techniques in patients with left
      sided breast cancer who had breast-conserving surgery. A three-dimensional
      computerized planning system (3DCPS) was used for each patient to compare wide
      field, oblique photon-electron, and perpendicular photon-electron techniques in
      terms of dose homogeneities in the target volume; the doses received by the
      contralateral breast, heart, and lung; and the coverage of the internal mammary
      chain. Data from 3DCPS were controlled by the Rando-phantom and
      thermoluminescence dosimetry. Critical structures were irradiated with acceptable
      dose percentages in addition to the internal mammary chain with both wide-field
      and photon-electron techniques. We detected more frequent hot spots in the
      oblique photon-electron technique than in the other techniques, and this
      situation necessitated changing the junctions. The wide-field technique was easy
      to perform and exposed less radiation dose to the heart than photon-electron
      techniques. In conclusion, we suggest the use of the wide-field technique in
      breast irradiation when the internal mammary area is in the target volume.

PMID- 19181256
TI  - Dosimetry of small circular fields for 6-MeV electron beams.
AB  - Small field electron beams used in the clinic present complex dosimetry. This
      investigation reports dosimetric characteristics of small 6-MeV electron field
      measurements and Monte Carlo calculations, and examines their impact on patient
      dosimetry. Radiographic film and ionization chamber were used for dosimetric
      measurements for a 6-MeV electron beam from a Varian 21EX linac. A set of
      circular cerrobend cutouts with diameters ranging from 2 to 3.0 cm was made. A
      clinical Monte Carlo algorithm was used to calculate dosimetric parameters. As
      the cutout diameter decreased, the build-up portion of the percentage depth dose
      (PDD) curves shifted toward the phantom surface, the depth of maximum dose,
      d(max,) decreased from 1.2 cm to 0.6 cm, but the practical range, R(p), remained
      constant at about 3.1 cm. The absorbed dose rate, D(r), decreased linearly with
      decreasing diameter. Profile coverage ratios CR (ie, the ratio of a given isodose
      line to the cutout diameter) at d(max), for 90% and 80%, CR(90), CR(80), are
      approximately 55% and 73%, respectively. As the cutout diameter decreased, the
      90% to 10% penumbra to diameter ratio, PR, increased from 0.49 to 0.56 for 3- to
      2-cm cutouts. The total 90% to 10% penumbra was about the same size as the cutout
      diameter. The measured output factors were in good agreement with Monte Carlo
      calculation within 2.2%. Accurate small electron field measurements were
      performed using parallel plate ion chamber and film. The data were well supported
      by Monte Carlo calculations. These data facilitate routine clinical treatments
      for small cutouts as d(max), D(r), and other data can be quickly obtained instead
      of performing labor-intensive individual patient measurements.

PMID- 19181257
TI  - Stereotactic radiotherapy for unilateral orbital lymphoma and orbital pseudo
      tumors: a planning study.
AB  - Orbital lymphoma and Grave's ophthalmopathy (GO) are successfully treated with
      radiation therapy. The lenses are blocked to prevent cataract formation. However,
      blocking of the lens by traditional methods can be difficult for tumors located
      anteriorly and extending into the retrobulbar space. We present a series of 3
      patients with orbital lymphoma and 1 with GO treated with stereotactic intensity
      modulated radiation therapy (IMRT) to spare normal structures, including the
      lens. Three patients with orbital lymphomas and 1 with unilateral GO were treated
      with IMRT using a linac with stereotactic capabilities. Avoidance structures
      included the ipsilateral lens and globe, the contralateral lens and globe, the
      chiasm, and the brainstem. Two patients with orbital lymphoma were treated with
      24 Gy in 12 fractions, and 1 patient was treated with 30.6 Gy in 17 fractions.
      The patient with GO was treated with 20 Gy in 10 fractions. The dosimetry was
      analyzed to determine the dose to normal tissues. Patient follow-up varies
      between 8 and 24 months. The mean minimal dose to the ipsilateral lens was 13.6%
      of the total dose, the mean maximal dose was 33.5%, and the mean median dose was
      19.3%. The mean median dose to the contralateral eye was 1.1% of the total dose.
      The mean median dose to the chiasm was 14.9% of the total dose. The mean median
      dose to the brainstem was 1.9% of the total dose. No cataracts or other
      complications were noted in the 4 patients treated with this technique so far.
      IMRT gives a more conformal treatment to the orbital contents while sparing
      normal tissues such as the ipsilateral lens and adjacent critical structures.
      This should result in fewer complications such as cataracts.

PMID- 19181258
TI  - Impact of surface curvature on dose delivery in intraoperative high-dose-rate
      brachytherapy.
AB  - In intraoperative high-dose-rate (IOHDR) brachytherapy, a 2-dimensional (2D)
      geometry is typically used for treatment planning. The assumption of planar
      geometry may cause serious errors in dose delivery for target surfaces that are,
      in reality, curved. A study to evaluate the magnitude of these errors in clinical
      practice was undertaken. Cylindrical phantoms with 6 radii (range: 1.35-12.5 cm)
      were used to simulate curved treatment geometries. Treatment plans were developed
      for various planar geometries and were delivered to the cylindrical phantoms
      using catheters inserted into Freiburg applicators of varying dimension. Dose
      distributions were measured using radiographic film. In comparison to the
      treatment plan (for a planar geometry), the doses delivered to prescription
      points were higher on the concave side of the geometry, up to 15% for the phantom
      with the smallest radius. On the convex side of the applicator, delivered doses
      were up to 10% lower for small treated areas (<or= 5 catheters) but,
      interestingly, the dose error was negligible for large treated areas (>5
      catheters). Our measurements have shown inaccuracy in dose delivery when the
      original planar treatment plan is delivered with a curved applicator. Dose
      delivery errors arising from the use of planar treatment plans with curved
      applicators may be significant.

PMID- 19181259
TI  - Preoperative radiation treatment for rectal cancer: comparison of target coverage
      and small bowel NTCP in conventional vs. 3D-conformal planning.
AB  - A prospective study was undertaken to evaluate the improvement in rectal cancer
      radiation treatment achieved with the implementation of target delineation for
      conformal radiotherapy, replacing conventional technique using standard
      radiological anatomy for target volume definition. In 10 patients receiving
      preoperative pelvic irradiation for rectal cancer, a 3-field technique was
      designed by a 3-dimensional (3D) planning system. Two plans were simulated for
      each patient, one with the fields designed in the conventional way based on
      radiological anatomy, and the other with the fields designed on the basis of a
      computed tomography (CT) delineated planning target volume (PTV). A total dose of
      45 Gy in 25-daily fractions of 1.8 Gy in 5 weeks was planned. Dose-volume
      histograms (DVHs) of PTV, small bowel, anal sphincter, and urinary bladder were
      analyzed to compare plans. The minimum, maximum, and mean dose in the PTV and in
      critical organs were also evaluated. The inhomogeneity coefficient (IC) and the
      target coverage (TC) were calculated. The normal tissue complication probability
      (NTCP) for each organ at risk (OAR) was determined. NTCP for small bowel and
      urinary bladder was not statistically different, while the PTV coverage was
      significantly lower with conventional treatment relative to conformal treatment
      (median IC=7.2, median TC=0.91 vs. median IC=0.14 and median TC=1, p<0.005). The
      3D conformal treatment plan in preoperative radiotherapy for rectal cancer
      improves target coverage without significantly affecting small bowel and urinary
      bladder NTCP.

PMID- 19181260
TI  - Upright 3D treatment planning using a vertical CT.
AB  - In this report, we describe a novel technique used to plan and administer
      external beam radiation therapy to a patient in the upright position. A patient
      required reirradiation for thymic carcinoma but was unable to tolerate the supine
      position due to bilateral phrenic nerve injury and paralysis of the diaphragm.
      Computed tomography (CT) images in the upright position were acquired at the
      Northern Illinois University Institute for Neutron Therapy at Fermilab. The CT
      data were imported into a standard 3-dimensional (3D) treatment planning system.
      Treatment was designed to deliver 24 Gy to the target volume while respecting
      normal tissue tolerances. A custom chair that locked into the treatment table
      indexing system was constructed for immobilization, and port films verified the
      reproducibility of setup. Radiation was administered using mixed photon and
      electron AP fields.

PMID- 19181261
TI  - Effective doses in four-dimensional computed tomography for lung radiotherapy
      planning.
AB  - The recent broad adoption of 4-D computed tomography (4DCT) scanning in
      radiotherapy has allowed the accurate determination of the target volume of
      tumors by minimizing image degradation caused by respiratory motion. Although the
      radiation exposure of the treatment beam is significantly greater than that of CT
      scans used for treatment planning, it is important to recognize and optimize the
      radiation exposure in 4DCT from the radiological protection point of view. Here,
      radiation exposure in 4DCT was measured with a 16 multidetector CT. Organ doses
      were measured using thermoluminescence radiation dosimeter chips inserted at
      respective anatomical sites of an anthropomorphic phantom. Results were compared
      with those with the helical CT scan mode. The effective dose measured for 4DCT
      was 24.7 mSv, approximately four times higher than that for helical CT. However,
      the increase in treatment accuracy afforded by 4DCT means its use in radiotherapy
      is inevitable. The patient exposure in the 4DCT could be of value by clarifying
      the advantage of the treatment planning using 4DCT.

PMID- 19181262
TI  - Nuclear Medicine and Biology 2009.

PMID- 19181263
TI  - Synthesis and characterization of [76Br]-labeled high-affinity A3 adenosine
      receptor ligands for positron emission tomography.
AB  - INTRODUCTION: Bromine-76-radiolabeled analogues of previously reported high
      affinity A(3) adenosine receptor (A(3)AR) nucleoside ligands have been prepared
      as potential radiotracers for positron emission tomography. METHODS: The
      radiosyntheses were accomplished by oxidative radiobromination on the N(6)-benzyl
      moiety of trimethyltin precursors. Biodistribution studies of the kinetics of
      uptake were conducted in awake rats. RESULTS: We prepared an agonist ligand
      {[(76)Br](1'S,2'R,3'S,4'R,5'S)-4'-{2-chloro-6-[(3-bromophenylmethyl)amino]purin-9
      yl}-1'-(methylaminocarbonyl)bicyclo[3.1.0]hexane-2',3'-diol (MRS3581)} in 59%
      radiochemical yield with a specific activity of 19.5 GBq/micromol and an
      antagonist ligand {[(76)Br](1'R,2'R,3'S,4'R,5'S)-4'-(6-(3-bromobenzylamino)-2
      chloro-9H-purin-9-yl)bicyclo[3.1.0]hexane-2',3'-diol (MRS5147)} in 65%
      radiochemical yield with a specific activity of 22 GBq/micromol. The resultant
      products exhibited the expected high affinity (K(i) approximately 0.6 nM) and
      specific binding at the human A(3)AR in vitro. Biodistribution studies in the rat
      showed uptake in the organs of excretion and metabolism. The antagonist MRS5147
      exhibited increasing uptake in testes, an organ that contains significant
      quantities of A(3)AR, over a 2-h time course, which suggests the presence of a
      specific A(3)AR retention mechanism. CONCLUSION: We were able to compare uptake
      of the [(76)Br]-labeled antagonist MRS5147 to [(76)Br]agonist MRS3581. The
      antagonist MRS5147 shows increasing uptake in the testes, an A(3)AR-rich tissue,
      suggesting that this ligand may have promise as a molecular imaging agent.

PMID- 19181265
TI  - Neuroimaging of the vesicular acetylcholine transporter by a novel 4-[18F]fluoro
      benzoyl derivative of 7-hydroxy-6-(4-phenyl-piperidin-1-yl)-octahydro
      benzo[1,4]oxazines.
AB  - Phenylpiperidinyl-octahydro-benzo[1,4]oxazines represent a new class of
      conformationally restrained vesamicol analogues. Derived from this morpholine
      fused vesamicol structure, a new fluorine-18-labeled 4-fluorobenzoyl derivative
      ([(18)F]FBMV) was synthesized with an average specific activity of 75
      GBq/micromol and a radiochemical purity of 99%. The radiolabeling method included
      an exchange reaction of a 4-nitro group of the precursor by fluorine-18, a
      reduction procedure to eliminate excess of the nitro compound, followed by a high
      performance liquid chromatography purification. [(18)F]FBMV demonstrates (i) a
      moderate lipophilic character with a logD(pH7.0) 1.8+/-0.10; (ii) a considerable
      binding affinity to the vesicular acetylcholine transporter (VAChT) (K(i)=27.5
      nM), as determined using PC12 cells transfected with a VAChT cDNA, and a low
      affinity to sigma(1,2) receptors (K(i) >3000 nM); (iii) a good uptake into the
      rat and pig brains; (iv) a typical accumulation in the VAChT-containing brain
      regions; and (v) an approximately 20% reduction in cortical tracer binding after
      a specific cholinergic lesion using 192IgG-saporin. [(18)F]FBMV exhibits another
      PET marker within the group of vesamicol derivatives that demonstrates potentials
      in imaging brain cholinergic deficits, while its usefulness in clinical practice
      must await further investigation.

PMID- 19181264
TI  - Dopamine transporter binding in rat striatum: a comparison of [O-methyl-11C]beta
      CFT and [N-methyl-11C]beta-CFT.
AB  - INTRODUCTION: Positron emission tomography scanning with radiolabeled
      phenyltropane cocaine analogs is important for quantifying the in vivo density of
      monoamine transporters, including the dopamine transporter (DAT). [(11)C]beta-CFT
      is useful for studying DAT as a marker of dopaminergic innervation in animal
      models of psychiatric and neurological disorders. [(11)C]beta-CFT is commonly
      labeled at the N-methyl position. However, labeling of [(11)C]beta-CFT at the O
      methyl position is a simpler procedure and results in a shorter synthesis time
      [desirable in small-animal studies, where specific activity (SA) is crucial]. In
      this study, we sought to validate that the O-methylated form of [(11)C]beta-CFT
      provides equivalent quantitative results to that of the more commonly reported N
      methyl form. METHODS: Four female Sprague-Dawley rats were scanned twice on the
      IndyPET II small-animal scanner, once with [N-methyl-(11)C]beta-CFT and once with
      [O-methyl-(11)C]beta-CFT. DAT binding potentials (BP identical
      withB'(avail)/K(d)) were estimated for right and left striata with a nonlinear
      least-squares algorithm, using a reference region (cerebellum) as the input
      function. RESULTS: [N-Methyl-(11)C]beta-CFT and [O-methyl-(11)C]beta-CFT were
      synthesized with 40-50% radiochemical yields (HPLC purification). Radiochemical
      purity was >99%. SA at end of bombardment was 258+/-30 GBq/micromol. Average BP
      values for right and left striata with [N-methyl-(11)C]beta-CFT were 1.16+/-0.08
      and 1.23+/-0.14, respectively. BP values for [O-methyl-(11)C]beta-CFT were 1.18+/
      0.08 (right) and 1.22+/-0.16 (left). Paired t tests demonstrated that labeling
      position did not affect striatal DAT BP. CONCLUSIONS: These results suggest that
      [O-methyl-(11)C]beta-CFT is quantitatively equivalent to [N-methyl-(11)C]beta-CFT
      in the rat striatum.

PMID- 19181266
TI  - 5-[18F]Fluoroalkyl pyrimidine nucleosides: probes for positron emission
      tomography imaging of herpes simplex virus type 1 thymidine kinase gene
      expression.
AB  - INTRODUCTION: The preliminary in vivo evaluation of novel 5-[(18)F]fluoroalkyl-2'
      deoxyuridines ([(18)F]FPrDU, [(18)F]FBuDU, [(18)F]FPeDU; [(18)F]1a-c,
      respectively) and 2'-fluoro-2'-deoxy-5-[(18)F]fluoroalkyl-1-beta-d
      arabinofuranosyl uracils ([(18)F]FFPrAU, [(18)F]FFBuAU, [(18)F]FFPeAU; [(18)F]1d
      f, respectively) as probes for imaging herpes simplex virus type 1 thymidine
      kinase (HSV1-tk) gene expression is described. METHODS: [(18)F]1a-f were
      successfully synthesized by a rapid and efficient two-step one-pot nucleophilic
      fluorination reaction using 5-O-mesylate precursors and [(18)F]F(-). For in vivo
      studies, tumor xenografts were grown in nude mice by implanting RG2 cells stably
      expressing HSV1-tk (RG2TK+) and wild-type cells (RG2). RESULTS: Biodistribution
      studies at 2 h pi revealed that the uptake of [(18)F]1a-b and [(18)F]1d-e in
      RG2TK+ tumors was not significantly different from control tumors. However,
      [(18)F]1c and [(18)F]1f had an average 1.6- and 1.7-fold higher uptake in RG2TK+
      tumors than control RG2 tumors. Blood activity curves for [(18)F]1c and [(18)F]1f
      highlight rapid clearance of radioactivity in the blood. Dynamic small animal PET
      (A-PET) imaging studies of tumor-bearing mice with [(18)F]1c and [(18)F]1f showed
      higher initial uptake (3.5- and 1.4-fold, respectively) in RG2TK+ tumors than in
      control tumors, with continued washout of activity from both tumors over time.
      CONCLUSIONS: Biological evaluations suggest that [(18)F]1c and [(18)F]1f may have
      limited potential for imaging HSV1-tk gene expression due to fast washout of
      activity from the blood, thus significantly decreasing sensitivity and
      specificity of tracer accumulation in HSV1-tk-expressing tumors.

PMID- 19181267
TI  - Synthesis and biodistribution of lipophilic and monocationic gallium
      radiopharmaceuticals derived from N,N'-bis(3-aminopropyl)-N,N'
      dimethylethylenediamine: potential agents for PET myocardial imaging with 68Ga.
AB  - INTRODUCTION: In locations that lack nearby cyclotron facilities for radionuclide
      production, generator-based (68)Ga radiopharmaceuticals might have clinical
      utility for positron emission tomography (PET) studies of myocardial perfusion
      and other physiological processes. METHODS: The lipophilic and monocationic
      (67)Ga-labeled gallium chelates of five novel hexadentate bis(salicylaldimine)
      ligands the bis(salicylaldimine), bis(3-methoxysalicylaldimine), bis(4
      methoxysalicylaldimine), bis(6-meth,oxysalicylaldimine), and bis(4,6
      dimethoxysalicylaldimine) of N,N'-bis(3-aminopropyl)-N,N'-dimethylethylenediamine
      (BAPDMEN), were prepared. The structure of the unlabeled [Ga(4
      MeOsal)(2)BAPDMEN](+)PF(6)(-) salt was determined by X-ray crystallography, and
      the biodistribution of each of the (67)Ga-labeled gallium chelates was determined
      in rats following intravenous administration and compared with the
      biodistribution of [(86)Rb]rubidium chloride. RESULTS: The [Ga(4
      MeOsal)(2)BAPDMEN](+)PF(6)(-) complex exhibited the expected pseudo-octahedral
      N(4)O(2)(2-) coordination sphere about the Ga(3+) center with a trans disposition
      of the phenolate oxygen atoms. All five (67)Ga radiopharmaceuticals were found to
      afford the desired myocardial retention of the radiogallium. The [(67/68)Ga][Ga(3
      MeOsal)(2)BAPDMEN](1+) radiopharmaceutical appears to have the best properties
      for myocardial imaging, exhibiting 2% of the injected dose in the heart 1 min and
      2 h postinjection and very high heart/nontarget ratios (heart/blood ratios of
      7.6+/-1.0 and 54+/-10 at 1 and 120 min, respectively; heart/liver ratios of 1.8+/
      0.4 and 39+/-3 at 1 and 120 min, respectively). CONCLUSIONS: Most of these new
      agents, particularly [(67/68)Ga][Ga(3-MeOsal)(2)BAPDMEN](1+), would appear
      superior to previously reported bis(salicylaldimine) ligands of N,N'-bis(3
      aminopropyl)ethylenediamine as candidates for PET imaging of the heart with
      (68)Ga.

PMID- 19181268
TI  - Biodistribution and metabolism of the anti-influenza drug [11C]oseltamivir and
      its active metabolite [11C]Ro 64-0802 in mice.
AB  - INTRODUCTION: Oseltamivir phosphate (Tamiflu) is an orally active anti-influenza
      drug, which is hydrolyzed by esterase to its carboxylate metabolite Ro 64-0802
      with potent activity to inhibit the influenza virus. The abnormal behavior and
      death associated with the use of oseltamivir have developed into a major problem
      in Japan where Tamiflu is often prescribed for seasonal influenza. It is critical
      to determine the amount of oseltamivir and Ro 64-0802 in the human brain and to
      elucidate the relationship between their amounts and neuropsychiatric side
      effects. The aim of this study was to evaluate [(11)C]oseltamivir and [(11)C]Ro
      64-0802 in mice as promising positron emission tomography (PET) ligands for
      measuring their amounts in living brains. METHODS: Whole-body biodistribution of
      [(11)C]oseltamivir and [(11)C]Ro 64-0802 was determined in mice using the
      dissection method and micro-PET. In vitro and in vivo metabolite assay was
      performed in the plasma and brain of mice. RESULTS: Between 1 and 60 min after
      injection of [(11)C]oseltamivir and [(11)C]Ro 64-0802, 0.20-0.06% and 0.39-0.03%
      ID/g were detected in the mouse brains, respectively (dissection method).
      Radioactivity concentrations in the living brains between 0 and 90 min after
      injection were measured at standardized uptake values of 0.25-0.05 for
      [(11)C]oseltamivir and 0.38-0.02 for [(11)C]Ro 64-0802 (micro-PET). In vivo
      metabolite assay demonstrated the presence of [(11)C]oseltamivir and [(11)C]Ro 64
      0802 in the brains after [(11)C]oseltamivir injection. CONCLUSION: This study
      determined the distribution and metabolism of [(11)C]oseltamivir and [(11)C]Ro 64
      0802 in mice. PET could be used to measure their amounts in the living brain and
      to elucidate the relationship between the amounts in the brain and the side
      effects of Tamiflu in the central nervous system.

PMID- 19181269
TI  - Detection of sites of infection in mice using 99mTc-labeled PN(2)S-PEG conjugated
      to UBI and 99mTc-UBI: a comparative biodistribution study.
AB  - The antimicrobial peptide ubiquicidin (UBI) directly labeled with technetium-99m
      ((99m)Tc) has recently been shown to be specifically taken up at sites of
      infection; however, its chemical structure is not well defined. To address this
      problem, the aim of the present study was to label UBI using poly(ethyleneglycol)
      N-(N-(3-diphenylphosphinopropionyl)glycyl)-S-tritylcysteine ligand (PEG-PN(2)S)
      in order to compare its ability to detect infection sites with that of (99m)Tc
      UBI. METHODS: The PN(2)S-PEG-UBI conjugate was prepared and labeled with (99m)Tc,
      and its radiochemical purity was subsequently assessed. The stability of the
      conjugate to cysteine challenge and dilution with both saline solution and
      phosphate buffer was determined and serum stability and protein binding were also
      assessed. In vivo studies were carried out in healthy mice to study the
      biodistribution of (99m)Tc-PN(2)S-PEG-UBI and its precursor (99m)Tc-PN(2)S-PEG
      and in infected mice to compare the uptakes of (99m)Tc-UBI and (99m)Tc-PN(2)S-PEG
      UBI at the site of infection using scintigraphic imaging and ex vivo tissue
      counting. RESULTS: (99m)Tc-PN(2)S-PEG-UBI was obtained with high radiochemical
      purity (98+/-1%) and high stability. The amphiphilic nature of the conjugate
      leads to a tendency to form micellar aggregates that explain the high protein
      binding values obtained. Biodistribution studies in mice showed low renal
      clearance followed by a predominant reticuloendothelial system clearance that
      limits its application in the abdominal area. Statistical analysis revealed no
      significant difference between (99m)Tc-UBI and (99m)Tc-PN(2)S-PEG-UBI uptake in
      infected mouse thigh, and the site of infection was clearly visualized using
      scintigraphic imaging. CONCLUSIONS: (99m)Tc-PN(2)S-PEG-UBI proved to be as
      effective as (99m)Tc-UBI in detecting sites of infection; however, the well
      defined chemical structure of (99m)Tc-PN(2)S-PEG-UBI makes it a better candidate
      for clinical imaging of infection.

PMID- 19181270
TI  - Uptake of 99mTc-labeled chondroitin sulfate by chondrocytes and cartilage: a
      promising agent for imaging of cartilage degeneration?
AB  - Chondroitin sulfate (CS) is used in the treatment of human osteoarthritis as a
      slow-acting symptomatic drug. For this reason, we performed uptake studies with
      (99m)TcCS using different chondrocyte cultures, as well as cartilage tissue in
      vitro. For uptake studies, adherent monolayer cultures of human chondrocytes (2.7
      x 10(4) cells/well) and (99m)TcCS (1 microCi) were used. In parallel, we also
      performed uptake studies with cell suspensions of human chondrocytes at 1 x 10(6)
      cells/well incubated with (99m)TcCS (5 microCi) under identical conditions.
      Uptake was studied also in cartilage tissue samples and frozen tissue sections
      for autoradiography. The uptake was monitored for 10-240 min, every 10-30 min for
      cell cultures and for cartilage tissue up to 72 h. As the commercially available
      drug Condrosulf (IBSA, Lugano, Switzerland) contains magnesium (Mg) stearate as
      additive, we investigated the uptake with and without this additive. The washout
      of the tracer was assessed after the uptake experiments with PBS buffer for
      different time intervals (10 min-3 h). Tracer uptake in monolayer+/-additives
      with low number of cells was low. With the use of chondrocytes in culture
      suspensions with higher number of cells, a higher uptake of 5.9+/-0.65% and 1.0+/
      0.1% (n=6) was found, with and without additive, respectively. The saturation was
      achieved after 100 min. With the use of human rib cartilage, the uptake of
      (99m)TcCS was continuously increasing with time and was very high with additive
      amounting to 101.8+/-5.2% vs. 53.0+/-8.3% (n=6) without after 72 h and showing
      delayed saturation up to 30 h. Thus, not only the resorption of the drug is
      enhanced by Mg-stearate, but also the uptake. The washout of the tracer from
      cartilage after 3 h of uptake amounted to 3.75+/-1.5% with additive vs. 13.1+/
      2.1% without. After 24 h, washout was lower amounting to 1.75+/-0.15% vs. 3.25+/
      0.25%, respectively. The autoradiographic studies paralleled the results of in
      vitro cartilage tissue uptake. These data show that (99m)TcCS accumulates in
      cartilage tissue, either by acting as a substrate for proteoglycan synthesis or
      by adsorption to cartilage. (99m)TcCS could therefore be a possible agent to
      target and radioimage osteoarthritis.

PMID- 19181271
TI  - Evaluation of 99mTc(CO)5I as a potential lung perfusion agent.
AB  - INTRODUCTION: The use of (99m)Tc-macroggregated albumin for lung perfusion
      imaging is well established in nuclear medicine. However, there have been safety
      concerns over the use of blood-derived products because of potential
      contamination by infective agents, for example, Variant Creutzfeldt Jakob
      Disease. Preliminary work has indicated that Tc(CO)(5)I is primarily taken up in
      the lungs following intravenous administration. The aim of this study was to
      evaluate the biodistribution and pharmacokinetics of (99m)Tc(CO)(5)I and its
      potential as a lung perfusion agent. METHODS: (99m)Tc(CO)(5)I was synthesized by
      carbonylation of (99m)TcO(4-) at 160 atm of CO at 170 degrees C in the presence
      of HI for 40 min. Radiochemical purity was determined by HPLC using
      (99)Tc(CO)(5)I as a reference. (99m)Tc(CO)(5)I was administered by ear-vein
      injection to three chinchilla rabbits, and dynamic images were acquired using a
      gamma camera (Siemens E-cam) over 20 min. Imaging studies were also performed
      with (99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) and (99m)TcO(4-) for
      comparison. (99m)Tc(CO)(5)I was administered intravenously to Sprague-Dawley
      rats, and tissue distribution studies were obtained at 15 min and 1 h
      postinjection. Comparative studies were performed using (99m)Tc-MAA. RESULTS:
      Radiochemical purity, assessed by HPLC, was 98%. The retention time was similar
      to that of (99)Tc(CO)(5)I. The dynamic images showed that 70% of (99m)Tc(CO)(5)I
      appeared promptly in the lungs and remained constant for at least 20 min. In
      contrast, (99m)TcO(4-) rapidly washed out of the lungs after administration. As
      expected (99m)Tc-MAA showed 90% lung accumulation. The percentage of injected
      dose per gram of organ +/-S.D. at 1 h for (99m)Tc(CO)(5)I was as follows: blood,
      0.22+/-0.02; lung, 12.8+/-2.87; liver, 0.8+/-0.15; heart, 0.15+/-0.01; kidney,
      0.47+/-0.08. The percentage of injected dose per organ +/-S.D. at 1 h was as
      follows: lung, 22.47+/-2.31; liver, 10.53+/-1.8; heart, 0.18+/-0.01; kidney,
      1.2+/-0.17. Tissue distribution studies with (99m)Tc-MAA showed 100% lung uptake.
      CONCLUSION: (99m)Tc(CO)(5)I was synthesized with a high radiochemical purity and
      showed a high accumulation in the lungs. Further work on the mechanism and
      optimization of lung uptake of (99m)Tc-pentacarbonyl complexes is warranted.

PMID- 19181273
TI  - Radiolabeled annexin V for imaging apoptosis in radiated human follicular thyroid
      carcinomas--is an individualized protocol necessary?
AB  - INTRODUCTION: Induction of apoptosis is a widely used strategy for cancer
      therapy, but evaluating the degree and success of this therapy still poses a
      problem. Radiolabeled annexin V has been proposed to be a promising candidate for
      detecting apoptotic cells in tumors following chemotherapy in vivo. In order to
      see whether radiolabeled annexin V could be a suitable substance for the
      noninvasive in vivo detection of apoptosis in thyroid tissue and to establish an
      optimized study protocol, we investigated two poorly differentiated thyroid
      carcinoma cell lines: ML-1 and FTC-133. METHODS: Apoptosis was evaluated before
      as well as 2 and 4 days after in vitro irradiation with 30 Gy X-rays. In this
      study, binding of FITC- and of (125)I-labeled annexin V was measured in
      comparison to other apoptosis markers such as Bax, caspase-3 and Fas, which were
      determined by flow cytometry and Western blot analysis with densitometric
      evaluation. RESULTS: ML-1 and FTC-133 cells showed a significant increase in
      annexin V binding 48 h after irradiation. Ninety-six hours after irradiation, the
      annexin V absorption capability of ML-1 cells was still maximal, while the living
      fraction of FTC-133 increased significantly. The amount of caspase-3 and Bax was
      clearly increased 48 h after irradiation and had normalized after 96 h in both
      cell lines. Fas protein concentrations remained unchanged in ML-1 cells but were
      significantly enhanced in FTC-133 cells. CONCLUSION: The binding of FITC- and
      (125)I-labeled annexin V showed a significant accordance. A reliable evaluation
      of apoptosis induced by radiotherapy in thyroid tumors was possible 48 h after
      irradiation, when binding of radiolabeled annexin V is most significantly
      enhanced. Using two poorly differentiated cell lines of thyroid carcinoma, one
      may expect to find a nearly similar response to external irradiation. In
      contrast, the cell lines showed a completely contrary response. However, an
      individualized study protocol for each type of tumor and probably within each
      type is necessary.

PMID- 19181272
TI  - Evaluating the potential of 188Re-SOCTA-trastuzumab as a new radioimmunoagent for
      breast cancer treatment.
AB  - INTRODUCTION: Radioimmunotherapy, which utilizes monoclonal antibodies and
      therapeutic radioisotopes against antigen-expressing tumor tissues, is an
      attractive therapeutic approach for cancer therapy. Trastuzumab (Herceptin) is a
      humanized anti-HER-2/neu monoclonal antibody for breast cancer treatment. In this
      paper, we introduce a new radioimmunoagent, (188)Re-trastuzumab, via a
      bifunctional ligand, succinimidyl 3,6-diaza-5-oxo-3-[2
      ((triphenylmethyl)thio)ethyl]-8-[(triphenylmethyl)thio]octanoate (SOCTA), and
      evaluate its potential to be a therapeutic radiopharmaceutical for breast cancer
      treatment. METHODS: Equimolar amounts of SOCTA and trastuzumab were selected to
      react, and the conjugation ratio of SOCTA-trastuzumab was evaluated by the MALDI
      TOF method. The immunoreactivity of SOCTA-trastuzumab was compared with
      nonconjugated trastuzumab in HER-2/neu overexpressing human breast cancer cell BT
      474. Biodistribution experiment and microSPECT/CT images of (188)Re-SOCTA
      trastuzumab being administered intravenously to SCID mice bearing xenografted BT
      474 breast cancer were investigated to evaluate the tumor-targeting capability.
      RESULTS: The covalent attachment of SOCTA to trastuzumab (at 1:1 molar ratio)
      resulted in the averaged conjugation ratio of 0.27+/-0.06 (n=3). The complex
      could easily be labeled with (188)Re and achieve 95% radiochemical purity (RCP)
      after 1 h of reaction at room temperature. The in vitro stability study also
      revealed that the RCP of (188)Re-SOCTA-trastuzumab was at a value of more than
      85% after 48 h of incubation with human serum. The immunoreactivity evaluation
      showed that SOCTA-trastuzumab and nonconjugated trastuzumab had similar binding
      capacity (B(max)) to HER-2/neu receptor in BT-474 cells. The animal experiments
      showed that (188)Re-SOCTA-trastuzumab accumulated more intensively in the tumor
      site as compared to normal tissue. CONCLUSION: We suggest that (188)Re-SOCTA
      trastuzumab could be a potential candidate for radioimmunotherapy.

PMID- 19181275
TI  - Cosmetic Rhinoplasty. Preface.

PMID- 19181274
TI  - Serum protein binding displacement: theoretical analysis using a hypothetical
      radiopharmaceutical and experimental analysis with 123I-N-isopropyl-p
      iodoamphetamine.
AB  - INTRODUCTION: The binding of radiopharmaceutical to serum proteins is thought to
      be an important factor that restricts its excretion and accumulation in tissue.
      We calculated the effect of inhibitors of serum protein binding using a
      hypothetical radiopharmaceutical. In vitro experiments and protein binding
      inhibitor-loaded monkey scintigraphy were then conducted using (123)I-N-isopropyl
      p-iodoamphetamine (IMP) as the radiopharmaceutical. METHODS: Free fraction ratios
      of radiopharmaceutical were calculated with one radiopharmaceutical, two serum
      proteins and two specific inhibitors in the steady state at various serum protein
      concentrations. In vitro protein binding inhibition studies using human, rat and
      monkey sera were performed with site-selective displacers of specific binding
      sites: 400 microM 6-methoxy-2-naphthylacetic acid (6MNA; a major nabumeton
      metabolite) as a serum albumin Site II inhibitor and 400 microM erythromycin
      (ETC) as an alpha(1)-acid glycoprotein (AGP) site inhibitor. Scintigraphy with or
      without 6MNA loading of monkeys was performed. RESULTS: The theoretical findings
      roughly corresponded to the experimental results. Approximately 75% of IMP bound
      to serum albumin Site II and AGP in the species examined. The free fraction of
      IMP (25.0+/-0.6% for human, 22.8+/-0.4% for monkey, 23.7+/-0.3% for rat)
      increased with loading of specific protein binding inhibitors (6MNA: 28.0+/-0.3%
      for human, 24.5+/-0.7% for monkey, 24.3+/-0.2% for rat; ETC: 26.3+/-0.4% for
      human, 29.5+/-1.1% for monkey, 26.0+/-0.7% for rat) and was serum protein
      concentration dependant based on the results of calculations. Simultaneous
      administration of 6MNA and ETC produced a higher free fraction ratio of IMP
      (31.9+/-1.0% for human, 34.6+/-0.4% for monkey, 27.0+/-0.3% for rat) than
      summation of the single administrations of 6MNA and ETC (domino effect) in human,
      rat and monkey sera. Rapid cerebral accumulation was observed with 6MNA loading
      in monkey scintigraphy. CONCLUSIONS: 6MNA appears to change the pharmacokinetics
      and brain accumulation of IMP in monkeys. Further studies in human are required.

PMID- 19181276
TI  - The rhinoplasty consultation and the business of rhinoplasty.
AB  - The business of rhinoplasty has undergone changes in keeping with increased
      competitive pressures locally, nationally, and internationally. Patient demands
      and progress in the field have abolished the "cookie-cutter" nose, with patients
      now requesting extensive discussions and predictions with computer photoimaging.
      The R-Factor Question and The D.O.S. Conversation are effective tools in
      rhinoplasty consultations. These tools provide patients with the clarity of what
      surgery can do for their lives and help patients overcome the fear produced by
      the overwhelming amount of information available. By helping our patients achieve
      the next level of success in their lives, we guarantee ourselves a busy practice
      filled with happy patients. The rhinoplasty consultation is the key to beginning
      this relationship of success.

PMID- 19181277
TI  - Preoperative, anesthetic, and postoperative care for rhinoplasty patients.
AB  - The perioperative period can be anxiety provoking for rhinoplasty patients.
      Patients rely on the skill and confidence of the surgeon to attain optimal
      results. Having an established strategy for the preoperative, anesthetic, and
      postoperative care of this patient population is critical to achieving a
      successful outcome and to ensuring a positive experience for the patient.
      Establishing a sincere rapport in the preoperative period and being able to
      properly address patient concerns regarding anesthesia helps patients develop a
      positive frame of mind and aids in their recovery. This presentation reviews
      important elements of the preoperative, anesthetic, and postoperative care of
      rhinoplasty patients and provides insight to making the experience a positive one
      for the patient and the surgeon.

PMID- 19181278
TI  - Nuances of profile management: the radix.
AB  - Profile refinement is one of the most common reasons patients seek consultation
      for rhinoplasty. Emphasis on creating a natural-appearing nasal dorsum demands a
      methodic nasal and facial analysis. Areas of dorsal excess and deficiency are
      identified, quantitated, and considered when determining surgical goals. The
      radix is an essential component of the profile and is carefully assessed from the
      standpoint of projection and position. Height and contour are evaluated at the
      radix, rhinion, and nasal tip. Each component of the dorsal profile is
      individually classified as overprojected, underprojected, or of appropriate
      height. Case studies demonstrate the necessary surgical steps to create a more
      balanced profile.

PMID- 19181279
TI  - Nasal tip dynamics.
AB  - In rhinoplasty, the nasal tip remains the most challenging anatomic region to
      diagnose and treat. This article presents a new concept, the M-arch model, to
      better understand the functional and aesthetic anatomy of the tip. This M-arch
      can be lengthened or shortened, or left as is, to establish the basis of ideal
      nasal length, projection, and rotation. Additional suture, incisional,
      excisional, and grafting maneuvers can be performed in a graduated fashion to
      further refine the M-arch, including the lobule and soft tissue of the nasal
      base. A full description of the M-arch model and its application is presented,
      and representative results are illustrated.

PMID- 19181280
TI  - Endonasal suture techniques in tip rhinoplasty.
AB  - Suture modification techniques have long served as reliable methods to surgically
      improve nasal tip contour by allowing control of width, projection, and rotation
      during rhinoplasty. Tip abnormalities characterized by a wide or broad shape are
      particularly amenable to such techniques. In the senior author's hands (SWP), the
      endonasal double-dome tip-sculpting technique has become a workhorse for the
      correction of the wide tip complex. When combined with additional techniques, the
      double-dome technique allows for the correction of various abnormalities falling
      under the umbrella of a broad tip (ie, boxy, bifid, bulbous, trapezoid,
      amorphous), while still adhering to the tenets of modern rhinoplasty philosophy.
      The authors present a paradigm for surgical planning, along with a series of case
      studies highlighting the capabilities of various suture techniques performed with
      the endonasal approach.

PMID- 19181281
TI  - New concepts in nasal tip contouring.
AB  - The authors introduce the concept of favorable shadowing of the nasal tip
      surface. Contouring the nasal tip is an advanced concept in rhinoplasty. Several
      tip altering techniques exist, but proper selection of an appropriate technique
      or combination of techniques first requires understanding of the impact of
      manipulating underlying tip structure on nasal surface topography. Frequently,
      maneuvers that narrow the domes, inappropriately create a pinched or unnatural
      appearing nasal tip. Many of these tip-narrowing techniques act to lower the
      caudal margin of the lateral crura below the cephalic margin and decrease support
      along the junction between the tip and alar lobule. The nasal tip skin can then
      collapse on this structure, creating a visible line of demarcation between the
      tip and alar lobule. Patients will describe their operated nasal tip as having
      the appearance of a round ball or bulbous tip, even thought their nasal tip may
      be narrow. This pinched appearance is due to the shadowing that isolates the
      nasal tip, creating a bulbous or pinched look to the nasal tip. Maneuvers such as
      dome sutures, lateral crural strut grafts, repositioning of the lateral crura,
      and alar rim grafts can create a favorable tip structure to support the
      underlying skin envelope. Using the methods described will enable the surgeon to
      focus less on narrowing the nasal tip and more on creating favorable shadowing of
      the nasal tip.

PMID- 19181282
TI  - Grafting in rhinoplasty.
AB  - Advances in grafting techniques have provided the basis for a paradigm shift in
      rhinoplasty in which purely reductive techniques have been largely supplanted by
      structurally sound framework surgery. Proficiency with autologous cartilage
      grafting allows the rhinoplasty surgeon to achieve superior nasal definition and
      durable aesthetic outcomes by building a stable nasal framework that resists the
      contractile forces of healing responsible for delayed nasal airway compromise and
      aesthetic distortion. Cartilage grafts may be used to reposition, augment, or
      reconstitute nasal structure after cartilaginous resection and recontouring. The
      authors present various grafting techniques that are reliably used to sculpt the
      nasal framework in rhinoplasty, with emphasis on the relevant anatomy,
      nomenclature, and clinical indications for each approach. Judicious use of these
      methods results in predictable rhinoplasty outcomes with enhanced aesthetics and
      function.

PMID- 19181283
TI  - Functional rhinoplasty.
AB  - The complete rhinoplasty surgeon must possess an understanding of functional
      nasal airway obstruction. An increasingly sophisticated grasp of the
      pathophysiology of fixed nasal obstruction has led surgeons to develop and refine
      surgical techniques aimed toward alleviating nasal valve insufficiency. This
      article reviews an assortment of techniques within nasal valve surgery,
      highlighting the underlying pathophysiology, anatomy, and technical
      considerations.

PMID- 19181284
TI  - Cleft lip rhinoplasty.
AB  - Many surgical approaches and techniques to repair cleft nasal deformities have
      been described. Because the presenting patient with a congenital deformity is
      young, the surgical plan must account for patient growth and surgical scarring.
      The surgeon should understand the pathophysiology of the deformity and have a
      systematic surgical plan. This article describes the classic nasal abnormalities
      associated with clefting of the lip, and outlines surgical techniques and timing
      used to minimize these deformities.

PMID- 19181285
TI  - Complications in rhinoplasty.
AB  - The surgical maneuvers employed in aesthetic rhinoplasty can result in unforeseen
      structural complications that lead to an unsatisfied patient. Many of these
      problems arise years after the primary surgery and include both aesthetic and
      functional losses. Contemporary rhinoplasty should always be designed with long
      term perspective and an eye on possible untoward outcomes. This article discusses
      the anatomic and physiologic basis of rhinoplasty complications with a focus on
      primary rhinoplasty principles that will prevent their formation.

PMID- 19181286
TI  - Tissue engineering for rhinoplasty.
AB  - Tissue engineering is a rapidly evolving field of research, and its impact on
      clinical health care solutions can be profound. It offers a unique opportunity to
      bridge the gap between basic science and the application of a tissue-engineered
      cartilage product for patients undergoing primary and revision rhinoplasty.
      Autologous tissue-engineered septal cartilage can be fabricated from a small
      sample of septal cartilage taken from a patient. This tissue-engineered product
      would eventually provide the surgeon with adequate grafting material with which
      to complete a rhinoplasty or nasal reconstructive case without the known
      limitations of tissue availability and tissue quantity. An update on this
      technology is presented as it relates to our field.

PMID- 19181287
TI  - Cognitive impairments in chronic heart failure: a case controlled study.
AB  - BACKGROUND: There are limited data describing the prevalence, type, and severity
      of cognitive impairments (CIs) in the general population with chronic heart
      failure (HF). The primary purpose of this study was to fill this gap in the
      literature by comparing the cognitive function of patients with chronic HF and
      community-dwelling control subjects. METHODS AND RESULTS: A case controlled
      design was used. Fifty patients with HF were recruited and matched to 50 healthy
      control subjects on age (+/- 3 years), gender, and estimated intelligence
      (intelligence quotient +/- 1 standard deviation). In the patient sample, mean
      left ventricular ejection fraction was 27% +/- 14%, 22 patients had New York
      Heart Association (NYHA) class II, 23 patients had NYHA class III, and 5 patients
      had NYHA class IV heart disease. Neuropsychologic tests assessed cognitive
      outcomes in orientation, attention, memory, executive function, motor speed, and
      reaction times. Patients had significantly poorer scores than controls on 14 of
      19 variables assessed. After standardization of the neuropsychologic test scores
      to T-scores (mean 50 +/- 10 SD), 23 patients (46%) had mild to severe CI and 8 of
      the control subjects had mild CI. Both patients and controls were impaired in 1
      or more of the 4 memory outcomes assessed. Logistic regression analysis indicated
      CI was independently associated with HF (odds ratio = 4.47, confidence interval =
      1.75-11.43, P < .002). Severity of CI was associated with depressed learning (P <
      .0001), previous myocardial infarction (MI) (P < .02), and the number of MIs (P <
      .01). CI severity was not associated with LVEF, HF duration, NYHA class, anxiety,
      depression, positive affect, social support, or physical functioning. Severity of
      MI (>or=2 MIs) was associated with deficits in early recall (P < .01), delayed
      recall (P < .03), and learning (P < .03). In contrast, patients with idiopathic
      or hypertensive cardiomyopathies without coronary artery disease when compared
      with patients with greater MI severity were not cognitively impaired on these
      outcome variables. CONCLUSION: The prevalence, type, and severity of CI in the
      community-dwelling patients with HF are consistent with the results found in
      patients with end-stage HF awaiting heart transplantation. Patients with heart
      failure incur a more than 4-fold risk for CI compared with matched community
      controls. The relationship of MI severity to deficits in memory outcomes and
      learning suggests that ischemic cardiomyopathy may be a significant factor in the
      development of CI in heart failure.

PMID- 19181288
TI  - Nationwide frequency and association of heart failure on stroke outcomes in the
      United States.
AB  - BACKGROUND: Few studies of the effect of heart failure (HF) on stroke outcomes
      have been published. This study was designed to determine the association of co
      existing HF with in-hospital length-of-stay (LOS), cost, and mortality among
      acute stroke patients admitted to hospitals in the United States (US). METHODS
      AND RESULTS: All patients with a primary diagnosis of stroke admitted to the US
      hospitals in calendar years 1995 and 2005 were extracted using the National
      Inpatient Sample (NIS) database. Patients were categorized based on a secondary
      diagnosis of HF. Patients' demographics, LOS, in-hospital death, disposition, and
      hospitalization costs were determined. The odds ratio of in-hospital mortality
      rates for stroke patients with HF were 2.5 (95% CI: 2.4-2.7) and 2.2 (95% CI: 2.0
      2.3) in 1995 and 2005, respectively, compared to those without HF. Stroke
      patients with HF also stayed longer in the hospital in both years studied, though
      a general decline in LOS was observed in 2005. The estimated increase in total
      hospitalization cost for stroke patients with HF was $1,100 (20% difference, 95%
      CI: 18%-23%) and $1,300 (18% difference, 95% CI: 16%-20%) for 1995 and 2005,
      respectively. CONCLUSIONS: The results of our study suggest that there is an
      association between co-existing HF and mortality in stroke patients. Stroke
      patients with HF appear to have a higher mortality rate, longer LOS, and higher
      hospitalization cost compared to those without HF. The mechanism of higher stroke
      mortality and morbidity in patients with HF requires further investigation to
      identify modifiable factors and to tailor better treatment options.

PMID- 19181289
TI  - Quality of life and depressive symptoms in the elderly: a comparison between
      patients with heart failure and age- and gender-matched community controls.
AB  - BACKGROUND: Comparisons of heart failure (HF) patients with an unselected healthy
      sample in terms of quality of life (QoL) and depressive symptoms might prove
      misleading. We compared QoL and depressive symptoms of a HF population with an
      age- and gender-matched sample of community dwelling elderly. METHODS AND
      RESULTS: Data were collected from 781 HF patients (36% female; age 72 +/- 9; New
      York Heart Association II-IV) and 781 age- and gender-matched community-dwelling
      elderly. Participants completed the Medical Outcome Study 36-item General Health
      Survey, the Cantril's Ladder of life, and the Center for Epidemiological Studies
      Depression scale (CES-D). Analysis of variance techniques with Welch F test and
      chi-square tests were used to describe differences in QoL and depressive symptoms
      between different groups. For both men and women with HF, QoL was reduced and
      depressive symptoms were elevated when compared with their elderly counterparts
      (CES-D >or=16: 39% vs. 21%, P < .001). HF patients had more chronic conditions
      specifically diabetes and asthma/chronic obstructive pulmonary disease. Impaired
      QoL and depressive symptoms were most prevalent among HF patients with
      comorbidities. Prevalence was also higher in HF patients in the absence of these
      conditions. CONCLUSIONS: HF has a large impact on QoL and depressive symptoms,
      especially in women with HF. Differences persist, even in the absence of common
      comorbidities. Results demonstrate the need for studies of representative HF
      patients with direct comparisons to age- and gender-matched controls.

PMID- 19181290
TI  - A comparative study of pain in heart failure and non-heart failure veterans.
AB  - BACKGROUND: Progress has been made in addressing pain in specific diseases such
      as cancer, but less attention has focused on understanding pain in nonmalignant
      states, including heart failure (HF). METHODS AND RESULTS: From March 2006 to
      June 2007, 672 veterans were surveyed and scores for the Brief Pain Inventory,
      pain distress, clinically significant pain levels (moderate to severe pain), and
      pain locations were compared using univariate and multivariate models. Fifteen
      percent of the final sample had HF (95/634). In our study, the HF patients were
      older (P < .000), reported lower levels of general health (P = .018), had more co
      morbidities (P < .000), were more likely to have a history of cancer (P = .035),
      and suffered more chest pain and fewer headaches (P = .026, P = .03,
      respectively) than their non-HF cohorts. When controlling for age, co-morbidity
      and cancer disorders, HF and non-HF patients did not differ in pain severity,
      interference, distress or locations. Of the patients currently experiencing pain,
      67.3% of HF patients and 68.4% of non-HF patients rated their pain as moderate or
      severe (pain >or=4 on a 0 to 10 scale). CONCLUSIONS: Although HF has not been
      identified as a painful condition, this study suggests the burden of pain is
      significant for both HF and non-HF ambulatory care patients.

PMID- 19181291
TI  - Combined use of PDE5 inhibitors and nitrates in the treatment of pulmonary
      arterial hypertension in patients with heart failure.
AB  - BACKGROUND: Phosphodiesterase-5 (PDE5) inhibitors, which induce relaxation of
      smooth muscle with some selectivity for the pulmonary vasculature, are used in
      the treatment of pulmonary hypertension. In some patients, the use of PDE5
      inhibitors does not result in the desired magnitude of pulmonary vasodilation.
      The use of additional vasodilators to further reduce pulmonary vascular
      resistance is often accompanied by unacceptable reductions in systemic arterial
      pressure. METHODS AND RESULTS: In 3 patients with heart failure, pulmonary
      hypertension and low systemic arterial pressures treated with sildenafil,
      systemic nitrates were added to reduce pulmonary hypertension further.
      Hemodynamic measurements were made before and after addition of nitrates.
      Addition of systemic nitrates to sildenafil led to a reduction in mean pulmonary
      arterial pressure of 11 mm Hg, from 37 mm Hg to 26 mm Hg (P = .06), whereas mean
      systemic arterial pressure decreased by only 4 mm Hg, from 77 mm Hg to 73 mm Hg
      (P = .53). The ratio of pulmonary vascular resistance to systemic vascular
      resistance was reduced by 45% (P = .1). Treatment with sildenafil and nitrates
      was continued for two to eight months, with no episodes of marked systemic
      hypotension, syncope, or lightheadedness. CONCLUSIONS: These results suggest that
      addition of systemic nitrates to sildenafil results in a potentiation of
      vasodilation that is relatively selective for the pulmonary vasculature, and that
      this combination may be safe and effective in the treatment of pulmonary
      hypertension in patients with low systemic arterial pressures.

PMID- 19181292
TI  - Prognostic value of combined measurement of brain natriuretic peptide and
      triiodothyronine in heart failure.
AB  - BACKGROUND: Both low free triiodothyronine (fT3) and high brain natriuretic
      peptide (BNP) have been separately described as prognostic predictors for
      mortality in heart failure (HF). We investigated whether their prognostic value
      is independent. METHODS AND RESULTS: From January of 2001 to December of 2006, we
      prospectively evaluated 442 consecutive patients with systolic HF and no thyroid
      disease or treatment with drugs affecting thyroid function (age 65+/-12 years,
      mean +/- standard deviation, 75% were male, left ventricular ejection fraction
      33% +/- 10%, New York Heart Association (NYHA) class I and II: 63%, NYHA class
      III and IV: 37%). All patients underwent full clinical and echocardiographic
      evaluation and assessment of BNP and thyroid function. Both cardiac and all-cause
      mortality (cumulative) were considered as end points. During a median 36-month
      follow-up (range 1-86 months), 110 patients (24.8%) died, 64 (14.4%) of cardiac
      causes. Univariate Cox model predictors of all-cause mortality and cardiac death
      were age, body mass index, creatinine, hemoglobin, ejection fraction, NYHA class,
      BNP, fT3, and thyroxine level. Multivariate analysis selected age, NYHA class,
      hemoglobin, BNP, and fT3 as independent predictors for all-cause mortality and
      NYHA class, BNP, and fT3 as independent predictors for cardiac mortality.
      Patients with low fT3 and higher BNP showed the highest risk of all-cause and
      cardiac death (odds ratio 11.6, confidence interval, 5.8-22.9; odds ratio 13.8,
      confidence interval, 5.4-35.2, respectively, compared with patients with normal
      fT3 and low BNP). CONCLUSION: fT3 and BNP hold an independent and additive
      prognostic value in HF.

PMID- 19181293
TI  - B-type natriuretic peptide and impedance cardiography at the time of routine
      echocardiography predict subsequent heart failure events.
AB  - BACKGROUND: Detection of heart failure (HF) in stable outpatients can be
      difficult until an overt event occurs. This study sought to determine whether the
      combination of B-type natriuretic peptide (BNP) and impedance cardiography (ICG)
      could be used in a nonacute clinical setting to risk stratify and predict HF
      related events in stable outpatients. METHODS AND RESULTS: Patients undergoing
      routine outpatient echocardiography underwent ICG and BNP testing and were
      followed for one year for HF-related events (Emergency Department [ED] visit or
      hospitalization due to HF or all-cause death). A total of 524 patients were
      analyzed, resulting in 57 HF-related events; 16 ED visits, 17 hospitalizations,
      and 24 all-cause deaths. Using Cox regression analyses, BNP and systolic time
      ratio index (STRI) by ICG proved to be the strongest predictors of future HF
      related events. Patients with a BNP >100 pg/ml and STRI >0.45 sec(-1) had a
      significantly lower event-free survival rate than those with a high BNP and low
      STRI (67% versus 89%, P=.001). In patients with LV dysfunction only, if both BNP
      and STRI values were high, the relative risk of a HF-related event increased by
      12.5 (95 % C.I. 4.2-36.7), when compared with patients with a low BNP and low
      STRI (P<.001). CONCLUSIONS: In a nonacute clinical setting, both BNP and ICG
      testing can provide unique predictive power of long-term HF-related events in a
      stable cohort of patients with and without LV dysfunction.

PMID- 19181294
TI  - Cardiac contractility modulation electrical signals normalize activity,
      expression, and phosphorylation of the Na+-Ca2+ exchanger in heart failure.
AB  - BACKGROUND: Expression and phosphorylation of the cardiac Na(+)-Ca(2+) exchanger
      1 (NCX-1) are up-regulated in heart failure (HF). We examined the effects of
      chronic cardiac contractility modulation (CCM) therapy on the expression and
      phosphorylation of NCX-1 and its regulators GATA-4 and FOG-2 in HF dogs. METHODS
      AND RESULTS: Studies were performed in LV tissue from 7 CCM-treated HF dogs, 7
      untreated HF dogs, and 6 normal (NL) dogs. mRNA expression of NCX-1, GATA-4, and
      FOG-2 was measured using reverse transcriptase polymerase chain reaction, and
      protein level was determined by Western blotting. Phosphorylated NCX-1 (P-NCX)
      was determined using a phosphoprotein enrichment kit. Compared with NL dogs, NCX
      1 mRNA and protein expression and GATA-4 mRNA and protein expression increased in
      untreated HF dogs, whereas FOG-2 expression decreased. Compared with NL dogs, the
      level of P-NCX-1 normalized to total NCX-1 increased in untreated HF dogs (0.80+/
      0.10 vs 0.37+/-0.04; P < .05). CCM therapy normalized NCX-1 expression, GATA-4,
      and FOG-2 expression, and the ratio of P-NCX-1 to total NCX-1 (0.62+/-0.10).
      CONCLUSION: Chronic monotherapy with CCM restores expression and phosphorylation
      of NCX-1. These findings are consistent with previous observations of improved LV
      function and normalized sarcoplasmic reticulum calcium cycling in the left
      ventricles of HF dogs treated with CCM therapy.

PMID- 19181295
TI  - Effects of the beta3-adrenergic agonist BRL 37344 on endothelial nitric oxide
      synthase phosphorylation and force of contraction in human failing myocardium.
AB  - BACKGROUND: In nonfailing myocardium, beta(3)-adrenergic signaling causes a
      decrease in contractility via endothelial nitric oxide synthase (eNOS) activation
      and nitric oxide (NO) release. This study investigates the hypothesis that
      beta(3)-adrenergic signaling undergoes alterations in failing myocardium.
      METHODS: We compared eNOS- and beta(3)-adrenoceptor expression using Western blot
      analysis in human nonfailing myocardium versus failing myocardium. With the use
      of immunohistochemistry, we investigated the distribution of the beta(3)
      adrenoceptor protein and eNOS translocation and phosphorylation under basal
      conditions. beta(3)-adrenergic, eNOS activation, and inotropy were measured in
      failing myocardium using BRL37344 (BRL, a beta(3)-adrenoceptor agonist). RESULTS:
      beta(3)-adrenoceptor expression was increased in failing myocardium. Under basal
      conditions, Akt- and eNOS(Ser1177) phosphorylation were reduced in failing
      myocardium. During stimulation with BRL in failing myocardium, a further
      dephosphorylation of eNOS(Ser1177) and Akt was observed, whereas eNOS(Ser114)
      phosphorylation was increased. These results suggest a deactivation of eNOS via
      beta(3)-adrenergic stimulation. Nevertheless, BRL decreased contractility in
      failing myocardium, but this effect was not observed in the presence of the NO
      blocker L-NMA. In failing myocardium, the beta(3)-adrenoceptor was predominantly
      expressed in endothelial cells. In the cardiomyocytes, the beta(3)-adrenoceptor
      was mainly located at the intercalated disks. CONCLUSION: In failing
      cardiomyocytes, beta(3)-adrenergic stimulation seems to deactivate rather than
      activate eNOS. At the same time, beta(3)-adrenergic stimulation induced a NO
      dependent negative inotropic effect. Because beta(3)-adrenoceptors are expressed
      mainly in the endothelium in failing myocardium, our observations suggest a
      paracrine-negative inotropic effect via NO liberation from the cardiac
      endothelial cells.

PMID- 19181296
TI  - Noninvasive assessment of wall distensibility with the evaluation of diastolic
      epicardial movement.
AB  - BACKGROUND: Left ventricular (LV) wall stiffening plays an important role in the
      development of heart failure with preserved ejection fraction (HFpEF). Based on
      the linear elastic theory, we hypothesized that the evaluation of epicardial
      movement during diastole is helpful for the noninvasive assessment of LV wall
      distensibility. METHODS AND RESULTS: Based on the linear elastic theory, the
      epicardial movement index (EMI) was calculated on the echocardiogram as: [see
      text.] We calculated diastolic wall strain (DWS) as follows to examine whether
      DWS substitutes for EMI: [see text.] The animal study using hypertensive Dahl
      salt-sensitive rats, HFpEF model, and normotensive Dahl rats showed the
      significant and inverse correlation of EMI or DWS with myocardial stiffness
      constant. Preload alteration did not affect EMI or DWS. In the clinical study,
      the HFpEF patients had lower EMI and DWS than the normal volunteers and the
      asymptomatic patients with LV hypertrophy. CONCLUSIONS: The evaluation of
      epicardial movement may be useful in noninvasively assessing wall distensibility
      in the absence of LV systolic dysfunction.

PMID- 19181297
TI  - Cardiac resynchronization therapy improves renal function: importance of forward
      and backward failure.

PMID- 19181299
TI  - Outcomes comparison of surgical ventricular restoration versus heart
      transplantation: should we also consider the waiting list mortality?

PMID- 19181301
TI  - Extensive macular atrophy with pseudodrusen-like appearance: a new clinical
      entity.
AB  - PURPOSE: To describe a previously unreported clinical entity of progressive
      extensive macular atrophy and pseudodrusen-like appearance in middle-aged
      patients. DESIGN: Clinical, electrophysiologic, and molecular retrospective
      study. METHODS: The database of an outpatient clinic unit for genetic sensory
      diseases was screened for patients older than 40 years with uncharacterized
      macular dystrophy. Patients with extensive macular atrophy and pseudodrusen-like
      appearance were included. RESULTS: Eighteen patients of 45 records (40%) matched
      the inclusion criteria. Bilateral polycyclic well-delineated chorioretinal
      atrophy extending to the temporal vascular arcades, with a larger vertical axis
      and without sparing of the fovea featured the macular lesion. The pseudodrusen
      like appearance was widespread throughout the posterior pole and the peripheral
      retina. In the extreme periphery, paving stone lesions were located mostly in the
      inferior quadrants. In contrast to age-related macular degeneration, a rapid
      progression of the atrophy was observed with an early involvement of the foveal
      zone, thus leading to a severe visual loss. All the patients except 2 were
      legally blind at the end of the follow-up. Unlike age-related macular
      degeneration, in none of these patients did choroidal neovascularization develop.
      In all patients, the scotopic and photopic electroretinography responses were
      reduced. CONCLUSIONS: Extensive macular atrophy with pseudodrusen should be
      considered as a possible pattern of severe macular dystrophy occurring in the
      middle-aged adult.

PMID- 19181302
TI  - An in vivo confocal microscopy analysis of effects of topical antiglaucoma
      therapy with preservative on corneal innervation and morphology.
AB  - PURPOSE: To evaluate the long-term effects of preservative-free and preservative
      containing antiglaucoma eye drops on the tear secretion and ocular surface.
      DESIGN: Comparative retrospective study. METHODS: A total of 84 patients with
      bilateral primary open-angle glaucoma or ocular hypertension divided into 5
      groups according to type of topical hypotensive therapy and 20 healthy age
      matched volunteers were studied. Clinical tests (corneal sensitivity, Schirmer I
      test, and lachrymal film break-up time), and in vivo confocal microscopy were
      performed in all patients. RESULTS: A significant reduction of the scores was
      found between groups on topical hypotensive therapy and the control group in all
      clinical parameters studied (P < .05). In particular, the clinical scores were
      significantly lower in the preservative medication groups than in the
      preservative-free group (P < .05). The density of superficial epithelial cells
      was reduced in all glaucomatous patients, except for the preservative-free group
      (P > .05), with respect to control subjects (P < .001). On the contrary, the
      density of basal epithelial cells of glaucomatous preservative therapy groups was
      higher than control and preservative-free groups (P < .05). Stromal keratocyte
      activation and the number of beads were higher in all glaucoma preservative
      groups (P < .05). The number of sub-basal nerves was lower in all glaucoma groups
      than in the control group (P < .05) and tortuosity was significantly higher in
      glaucoma than control groups (P < .05). Reflectivity of fibers did not show any
      significant difference between the 6 groups (P < .05). CONCLUSIONS: Glaucomatous
      patients with chronic treatment show ocular surface alterations. The development
      of nontoxic antiglaucoma treatment may reduce damage to the ocular surface and
      improve the compliance and the adherence in the medical therapy.

PMID- 19181303
TI  - Glitazone use associated with diabetic macular edema.
AB  - PURPOSE: To determine the ocular safety of glitazones in patients with diabetes,
      we investigated the association of diabetic macular edema (DME) in a large
      population of glitazone users. DESIGN: Prospective cohort study. METHODS: The
      study was conducted at Kaiser Permanente Southern California. About 170,000
      persons with diabetes were identified using the Diabetes Case Identification
      Database. Glitazone drug use was obtained from the pharmacy database. The main
      outcome measure was the development of macular edema (ME). The chi2 test was used
      to compare proportions and t tests were used for means. Logistic regression
      analysis was used to adjust for potential confounding variables. RESULTS: In
      2006, there were 996 new cases of ME. Glitazone users were more likely to develop
      ME in 2006 (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.4 to 3.0).
      After excluding patients who did not have the drug benefit, did not have an eye
      exam, and had a HgA1c <7.0, glitazone use was still associated with an increased
      risk of developing ME (OR, 1.6; 95% CI, 1.4 to 1.8). CONCLUSION: The current
      study appears to show that the glitazone class of drug is associated with DME.
      After adjusting for confounding factors of age, glycemic control, and insulin
      use, glitazones are still modestly associated with DME. A more in-depth study
      will need to be done to evaluate the role of other confounding factors. When
      treating patients with DME, ophthalmologists should consider the role of the
      glitazones.

PMID- 19181304
TI  - Correlation among choroidal, parapapillary, and retrobulbar vascular parameters
      in glaucoma.
AB  - PURPOSE: To study and compare the correlation among choroidal, parapapillary, and
      retrobulbar vascular parameters in healthy subjects, glaucoma suspects, and open
      angle glaucoma (OAG) patients. DESIGN: Prospective observational clinical study.
      METHODS: The study included one randomly selected eye from 21 normal subjects, 30
      glaucoma suspects based on optic disc appearance, and 22 OAG patients. The
      pulsatile ocular blood flow (POBF), a measure of choroidal blood flow, was
      assessed using ocular blood flow analyzer whereas parapapillary blood flow and
      blood velocity of retrobulbar blood vessels were measured using scanning laser
      Doppler flowmetry and color Doppler imaging, respectively. All vascular
      parameters along with blood pressure and intraocular pressure measurements were
      obtained within a 2-hour period. Univariate regression analyses were used to
      evaluate the correlation of POBF values with parapapillary blood flow values,
      retrobulbar blood flow velocities, and resistive index, which represents vascular
      resistance, in each group. Two multiple linear regression models were created
      based on results of univariate analyses and included POBF, mean parapapillary
      blood flow, age, and mean ocular perfusion pressure; and POBF, temporal short
      posterior ciliary artery resistive index, age, and mean ocular perfusion
      pressure. RESULTS: POBF was significantly associated with parapapillary blood
      flow (r2 = 0.54; P < .001, positive correlation) and temporal short posterior
      ciliary artery resistive index (r2 = 0.39; P < .001, negative correlation) in
      normal subjects. Results were consistent when corrected for age, intraocular
      pressure, and blood pressure parameters. POBF values did not correlate with
      parapapillary blood flow values or temporal short posterior ciliary artery
      resistive index in glaucoma suspects or OAG patients. CONCLUSION: The
      relationships of POBF with parapapillary blood flow and calculated retrobulbar
      vascular resistance differs among normal subjects, glaucoma suspects, and OAG
      patients. This provides further evidence of vascular dysregulation in OAG.

PMID- 19181305
TI  - Enucleation for open globe injury.
AB  - PURPOSE: To report the experience of enucleation after open globe at an
      ophthalmic trauma referral center. DESIGN: Retrospective, observational study.
      METHODS: In an ophthalmic trauma referral center the charts of all patients
      having suffered an open globe injury between January 1, 2000 and June 30, 2007
      were reviewed. Variables assessed were age, gender, type of injury (rupture or
      laceration [penetrating, intraocular foreign body, or perforating]), ocular
      trauma score, visual acuity, subsequent enucleation, indication for and timing of
      enucleation, presence of sympathetic ophthalmia, and length of follow-up.
      RESULTS: Among 660 open globe injuries, 55 have undergone enucleation (including
      4 eviscerations), 11 primarily and 44 secondarily. Eyes with ruptures were
      significantly more likely to be enucleated than those with injuries attributable
      to lacerations (P < .001). The most common reason for secondary enucleation was a
      blind, painful eye. Two patients (0.3%) developed sympathetic ophthalmia and have
      maintained good vision in the sympathizing eye. CONCLUSIONS: The vast majority of
      open globes can be repaired without requiring primary enucleation. Secondary
      enucleation is most commonly carried out for pain. Eyes with no light perception
      can be closely observed if the patient chooses.

PMID- 19181306
TI  - Low rate of endophthalmitis in a large series of open globe injuries.
AB  - PURPOSE: To determine the percentage of patients in whom endophthalmitis
      developed after open globe injury. DESIGN: Retrospective, noncomparative,
      consecutive case series. METHODS: Charts of all patients (675 in total) treated
      surgically for open globe injury at the Massachusetts Eye and Ear Infirmary
      (MEEI) between January 1, 2000 and July 31, 2007 were reviewed. Cases with at
      least 30 days of follow-up were included in statistical analyses (558 in total).
      A standardized treatment protocol was used in all cases. Intravenous vancomycin
      and ceftazidime were started on admission and were stopped after 48 hours.
      Patients were discharged on topical antibiotics, corticosteroids, and
      cycloplegia. Surgical repairs were performed by the chief of trauma, a full-time
      position rotating yearly, who is on call for all open globe trauma. Data
      collection variables included timing of injury and repair, mechanism of injury,
      details of surgical repair, and details of follow-up such as duration, presence
      of complications, and vision. A primary outcome measure of endophthalmitis and
      secondary outcome measure of risk factors for endophthalmitis were studied.
      RESULTS: During 7.5 years, 675 open globe injuries were treated at MEEI. Of
      these, 558 had at least 30 days of follow-up (mean, 11 months) and were used in
      statistical analyses. The overall percentage of endophthalmitis was 0.9% (3
      culture-positive cases and 2 culture-negative cases). Four of the 5 cases
      achieved final acuity of 20/80 or better. Risk factors for endophthalmitis
      included intraocular foreign body (P = .03; odds ratio, 7.52) and primary
      intraocular lens placement (P = .05). CONCLUSIONS: A standardized protocol
      including surgical repair by a dedicated eye trauma service and 48 hours of
      intravenous antibiotics was associated with a posttraumatic endophthalmitis
      percentage of less than 1%.

PMID- 19181307
TI  - Self-rumination, self-reflection, and depression: self-rumination counteracts the
      adaptive effect of self-reflection.
AB  - Self-focused attention has adaptive and maladaptive aspects: self-reflection and
      self-rumination [Trapnell, P. D., & Campbell, J. D. (1999). Private self
      consciousness and the Five-Factor Model of personality: distinguishing rumination
      from reflection. Journal of Personality and Social Psychology, 76, 284-304].
      Although reflection is thought to be associated with problem solving and the
      promotion of mental health, previous researches have shown that reflection does
      not always have an adaptive effect on depression. Authors have examined the
      causes behind this inconsistency by modeling the relationships among self
      reflection, self-rumination, and depression. One hundred and eleven
      undergraduates (91 men and 20 women) participated in a two-time point assessment
      with a 3-week interval. Statistical analysis with structural equation modeling
      showed that self-reflection significantly predicted self-rumination, whereas self
      rumination did not predict self-reflection. With regard to depression, self
      reflection was associated with a lower level of depression; self-rumination, with
      a higher level of depression. The total effect of self-reflection on depression
      was almost zero. This result indicates that self-reflection per se has an
      adaptive effect, which is canceled out by the maladaptive effect of self
      rumination, because reflectors are likely to ruminate and reflect simultaneously.

PMID- 19181308
TI  - High impulsivity predicts relapse to cocaine-seeking after punishment-induced
      abstinence.
AB  - BACKGROUND: Relapse is a hallmark feature of cocaine addiction and a main
      challenge for treatment strategies. Human studies indicate a link between
      impulsivity and increased susceptibility to relapse. METHODS: Rats were screened
      for high (HI) and low impulsivity (LI) on the 5-choice serial reaction time task.
      The HI and LI rats were trained to self-administer cocaine under a seeking-taking
      chained schedule: responses on the seeking lever resulted in presentation of the
      taking lever, responding upon which resulted in cocaine reinforcement. After the
      establishment of stable responding, an intermittent punishment schedule was
      introduced: completion of the seeking link resulted in the random presentation of
      either the taking lever or a mild footshock. This resulted in a progressive
      decrease in cocaine-seeking approaching abstinence. Relapse was assessed 7 days
      after punishment, during which responding on the seeking lever resulted in the
      presentation of the cocaine-associated stimuli (i.e., in the absence of cocaine
      or footshock). RESULTS: The HI and LI animals significantly reinstated the
      cocaine-seeking response after a single phase of seeking punishment. However,
      after a second punishment phase only the HI rats reinitiated suppressed seeking
      responses and relapsed, an effect that was facilitated by prior extended cocaine
      access. In a preliminary study we found that the selective noradrenaline reuptake
      inhibitor, atomoxetine, a drug known to reduce impulsivity, prevented the
      reinstatement of cocaine-seeking. CONCLUSIONS: Impulsivity pre-dating drug abuse
      increases the susceptibility to relapse after abstinence. Medications targeting
      impulsivity might have utility as treatment interventions for relapse prevention
      and the promotion of abstinence.

PMID- 19181309
TI  - Trifluoroacetic acid-mediated facile transformation of 2-C-hydroxymethyl-D
      glycals to chiral pyrano[2,3-b]benzopyrans.
AB  - Treatment of 2-C-hydroxymethyl-D-glycals with phenols in trifluoroacetic acid at
      ambient temperature leads to an extremely facile transformation affording chiral
      pyrano[2,3-b]benzopyrans in high yields.

PMID- 19181310
TI  - Mycobacterium bovis Bacillus Calmette-Guerin (BCG)-induced activation of PI3K/Akt
      and NF-kB signaling pathways regulates expression of CXCL10 in epithelial cells.
AB  - CXCL10 production is a critical step in limiting mycobacterial infection.
      Although induction of this chemokine by mycobacteria in epithelial cells has been
      reported, it is still unclear how CXCL10 is regulated in Mycobacterium bovis BCG
      infected epithelial cells. In this study, we demonstrate that
      phosphatidylinoditol 3-kinase (PI3K)/Akt and the nuclear factor kB (NF-kB)
      signaling pathways play an important role in CXCL10 expression at the protein and
      mRNA level in A549 cells. We demonstrate that treatment of A549 cells with
      LY294002 and wortmannin, two PI3K inhibitors, inhibited M. bovis BCG-induced
      CXCL10 expression. In addition, treatment of A549 cells with an Akt inhibitor
      significantly blocked M. bovis BCG-induced CXCL10 production. Moreover, our data
      show that treatment of epithelial cells with CAPE, BAY 11-7082, and PDTC three
      selective inhibitors of NF-kB, significantly reduced the effect of M. bovis BCG
      on induced CXCL10 mRNA expression (74%, 69% and 83% inhibition by 8microM CAPE,
      10microM BAY 11-7082 and 3microM PDTC as assessed by real-time PCR,
      respectively). In accordance with the gene induction, the production of CXCL10
      was also significantly reduced by these inhibitors. Finally, the inhibition of
      PI3K affect NF-kB activation in M. bovis BCG-infected cells, indicating that PI3K
      activity is required for the M. bovis BCG-induced activation of NF-kB. The
      functional association between PI3K/Akt and NF-kB demonstrates another mechanism
      in the regulation of M. bovis BCG-induced CXCL10 in A549 cells.

PMID- 19181311
TI  - Fast simulation of ultrasound images from a CT volume.
AB  - The goal of our work is to propose a fast ultrasound image simulation from CT
      volumes. This method is based on a model elaborated by Bamber and Dickinson that
      predict the appearance and properties of a B-Scan ultrasound image from the
      distribution of point scatterers. We propose to extend this model for the
      standard medical ultrasound image simulation by taking into account the
      acoustical tissue properties (scatterer distribution) and the geometry and the
      specifications of the ultrasound probe (circular probe, number and size of
      transducers, US pulse frequency and bandwidth, etc.). Simulations have been
      obtained in a fairly fast computation speed and qualitatively they present most
      of the real ultrasound image characteristics.

PMID- 19181312
TI  - Metabolism and excretion kinetics of 14C-labeled and non-labeled difloxacin in
      pigs after oral administration, and antimicrobial activity of manure containing
      difloxacin and its metabolites.
AB  - Fluoroquinolones are amongst the most important antibiotics used in veterinary
      medicine. On this account the behavior of difloxacin (DIF) and its metabolites
      was investigated by administering the (14)C-labeled and non-labeled veterinary
      drug to fattening pigs. The excretion kinetics were determined after daily
      collection of manure. Sarafloxacin (SAR) was found to be the major metabolite,
      three further trace metabolites were also recovered, applying high-resolution
      (HR) mass spectrometric technique. The identification of DIF and SAR was
      confirmed by comparison with the spectroscopic and chromatographic data of the
      authentic references. The identification of the three trace metabolites was
      performed by HR-MS/MS. Only 8.1% of the administered radioactivity remained in
      the pig after 10 days and DIF accounted for 95.9% of the radioactivity excreted.
      More than 99% of the labeled compounds were detected and identified in the
      manure. The mean recoveries for all single electrolytes were 94%. Linearity was
      established over concentration range 10-10,000 microg/kg manure with a
      correlation coefficient 0.99. By using in vitro antimicrobial activity tests
      against a group of standard pathogenic control strains, the results showed that
      the residual antibiotic concentrations in the manure of pigs are high enough to
      exhibit antibacterial activity.

PMID- 19181313
TI  - Polycyclic aromatic hydrocarbon-DNA adducts and survival among women with breast
      cancer.
AB  - Polycyclic aromatic hydrocarbons (PAH) are mammary carcinogens in animal studies,
      and a few epidemiologic studies have suggested a link between elevated levels of
      PAH-DNA adducts and breast cancer incidence. An association between PAH-DNA
      adducts and survival among breast cancer cases has not been previously reported.
      We conducted a survival analysis among women with newly diagnosed invasive breast
      cancer between 1996 and 1997, enrolled in the Long Island Breast Cancer Study
      Project. DNA was isolated from blood samples that were obtained from cases
      shortly after diagnosis and assayed for PAH-DNA adducts using ELISA. Among the
      722 cases with PAH-DNA adduct measurements, 97 deaths (13.4%) from all causes and
      54 deaths (7.5%) due to breast cancer were reported to the National Death Index
      (NDI) by December 31, 2002. Using Cox proportional hazards models and controlling
      for age at diagnosis, we did not find evidence that all-cause mortality (hazard
      ratio (HR)=0.88; 95% confidence interval (CI): 0.57-1.37), or breast cancer
      mortality (HR=1.20; 95% CI: 0.63-2.28) was strongly associated with detectable
      PAH-DNA adduct levels compared with non-detectable adducts; additionally, no dose
      response association was observed. Among a subgroup with treatment data (n=520),
      adducts were associated with over a two-fold higher mortality among those
      receiving radiation, but mortality for adducts was reduced among hormone therapy
      users. Results from this large population-based study do not provide strong
      support for an association between detectable PAH-DNA adducts and survival among
      women with breast cancer, except perhaps among those receiving radiation
      treatment.

PMID- 19181314
TI  - Temporal trends in bull semen quality: a comparative model for human health?
AB  - INTRODUCTION: A decline in human semen quality over the past 30-60 years has been
      reported in numerous epidemiological studies from the United States and Europe.
      We evaluated temporal trends in semen quality parameters in dairy bulls. The long
      term management of dairy bulls for artificial insemination presented a unique
      opportunity to evaluate temporal trends in semen quality and explore this
      relationship as a potential animal model for reproductive abnormalities in
      humans. MATERIALS AND METHODS: Bull semen analysis data from 1965 through 1995
      were collected from a large artificial insemination organization. Semen analyses
      from 12- to 18-month-old Holstein dairy bulls were included in the study and
      consisted of daily sperm concentration, daily ejaculate volume, total daily sperm
      output, percentage of sperm with normal morphology, and percentage of sperm with
      normal post-thaw motility. Multiple regression analysis, logistic regression, and
      general linear modeling were used to determine temporal trends over the 30-year
      period. RESULTS AND DISCUSSION: Semen quality appears to have declined from 1970
      to 1980 or 1985 as manifested by declines in daily ejaculate volume, daily sperm
      concentration, and total daily sperm output. In contrast, sperm morphology and
      motility improved over the same period. In approximately 1980 or 1985, depending
      on the parameter, ejaculate volume, sperm concentration, total sperm, and
      motility improved. However, normal morphology began to deteriorate during this
      same period. Methodological inconsistencies over time introduce uncertainty in
      analyses of temporal trends in semen quality in this and previous human studies.
      However, changes in technology do not appear to be solely responsible for the
      temporal trends observed. The source of the decline in semen quality in the bulls
      studied is unknown. If the decline in semen quality were due to exposure to
      endocrine disrupting chemicals, then a continued decline or a leveling-off would
      be expected. Instead, a rise in semen quality was observed during the latter
      portion of the observation period.

PMID- 19181315
TI  - Circulating fibroblast growth factor-23 is associated with vascular dysfunction
      in the community.
AB  - OBJECTIVE: Subjects with chronic kidney disease (CKD) are at higher risk for
      cardiovascular (CV) disease than the general population. These patients have
      elevated circulating levels of FGF23, which predict for increased mortality in
      CKD patients on hemodialysis. Since CV disease is a major cause of death in CKD,
      we investigated the association between FGF23 and vascular function. METHODS AND
      RESULTS: We employed a community-based cohort of subjects aged 70, the PIVUS
      study (n=967), to investigate the relation between serum FGF23, endothelium
      function and arterial stiffness. Higher FGF23 was weakly associated with both
      impaired endothelium-dependent (beta=-0.08, p<0.05) and endothelium-independent
      (beta=-0.08, p<0.01) vasodilation. The association was stronger in subjects with
      eGFR> or =90mL/min/1.73m(2) (beta=-0.19 and beta=-0.22, respectively, p<0.001).
      In addition, higher FGF23 was associated with increased arterial stiffness
      exclusively in subjects with an age-adjusted impaired renal function
      (eGFR<60mL/min/1.73m(2)) (beta=0.26, p<0.001). All associations were independent
      of gender, biochemical covariates and established CV risk factors. CONCLUSIONS:
      Higher serum FGF23 levels, even within the normal range, are independently
      associated with impaired vasoreactivity and increased arterial stiffness in the
      community. Additional studies are required to determine possible direct vascular
      effects of FGF23 and whether FGF23 is a modifiable CV risk factor.

PMID- 19181316
TI  - ADMA and SDMA levels in healthy men exposed to tobacco smoke.

PMID- 19181317
TI  - Immigration presents a potential increased risk for atherosclerosis.
AB  - OBJECTIVE: Immigrants in Western countries tend to have a greater risk for
      cardiovascular disease (CVD) than those in their home country, but it is unclear
      if immigrants are at increased risk for CVD compared to non-immigrants in their
      new country. The purpose of this study was to determine the independent
      association of time since immigration with sub-clinical atherosclerosis in
      immigrants of Chinese, European and South Asian origin. METHODS: A total of 460
      immigrants and 158 non-immigrants of Chinese, European and South Asian origin
      without pre-diagnosed CVD were assessed for sub-clinical atherosclerosis by
      carotid artery ultrasound scan, socio-demographics, CVD risk factors and
      lifestyle factors. Time since immigration in years was used as a measure of
      exposure. RESULTS: Participants who immigrated > or =30 years ago had a greater
      intima-media thickness (IMT) of the carotid artery compared to non-immigrants,
      and immigrants of < or =20 years. Time since immigration was associated with IMT,
      plaque area and IMT+plaque area. After adjustment for age, sex, ethnicity,
      income, education, family history of CVD and diabetes, smoking, physical
      activity, body mass index, visceral adipose tissue, lipids, insulin, glucose and
      blood pressure, time since immigration was significantly associated with IMT. For
      every ten years since immigration there was a 2% increase in IMT in addition to
      the 7% increase for every 10 years of age. CONCLUSIONS: Immigration was
      associated with an increased burden of sub-clinical atherosclerosis that
      surpassed that of non-immigrants. This burden increased over time independent of
      other risk factors. Immigrants represent a high-risk group for which targeted
      interventions are needed.

PMID- 19181318
TI  - Effects of suppression of bone turnover on cortical and trabecular load sharing
      in the canine vertebral body.
AB  - The relative biomechanical effects of antiresorptive treatment on cortical
      thickness vs. trabecular bone microarchitecture in the spine are not well
      understood. To address this, T-10 vertebral bodies were analyzed from skeletally
      mature female beagle dogs that had been treated with oral saline (n=8 control) or
      a high dose of oral risedronate (0.5mg/kg/day, n=9 RIS-suppressed) for 1 year.
      Two linearly elastic finite element models (36-mum voxel size) were generated for
      each vertebral body-a whole-vertebra model and a trabecular-compartment model-and
      subjected to uniform compressive loading. Tissue-level material properties were
      kept constant to isolate the effects of changes in microstructure alone.
      Suppression of bone turnover resulted in increased stiffness of the whole
      vertebra (20.9%, p=0.02) and the trabecular compartment (26.0%, p=0.01), while
      the computed stiffness of the cortical shell (difference between whole-vertebra
      and trabecular-compartment stiffnesses, 11.7%, p=0.15) was statistically
      unaltered. Regression analyses indicated subtle but significant changes in the
      relative structural roles of the cortical shell and the trabecular compartment.
      Despite higher average cortical shell thickness in RIS-suppressed vertebrae
      (23.1%, p=0.002), the maximum load taken by the shell for a given value of shell
      mass fraction was lower (p=0.005) for the RIS-suppressed group. Taken together,
      our results suggest that-in this canine model-the overall changes in the
      compressive stiffness of the vertebral body due to suppression of bone turnover
      were attributable more to the changes in the trabecular compartment than in the
      cortical shell. Such biomechanical studies provide an unique insight into higher
      scale effects such as the biomechanical responses of the whole vertebra.

PMID- 19181319
TI  - Contrast enhancement of speckle patterns from blood in synchrotron X-ray imaging.
AB  - Hemodynamics has been a very important factor in understanding and diagnosing
      various vascular diseases. Recently, the X-ray particle image velocimetry (X-ray
      PIV) method using speckle patterns of blood has been introduced as a new
      quantitative visualization method for blood flows without any seeding tracer or
      contrast agents. In this study, the peculiar optical characteristics of blood on
      the synchrotron X-ray imaging method, which were not presented in previous
      studies, were investigated in depth and systematically. The experimental
      conditions required for X-ray PIV application were found to be the distance
      between the sample and the scintillator ( approximately 40cm), the thickening of
      the blood sample (>0.3mm), and hematocrit (20.0-80.0%). In addition, we verified
      that the X-ray PIV method is reliable as an advanced flow velocimetry by
      comparing the flow rate evaluated from the X-ray PIV result and the input flow
      rate supplied from a syringe pump with an error of less than 1%. Through this
      study, based on the understanding of contrast enhancement mechanisms of speckle
      patterns from blood, we could establish a trustworthy flow visualization method
      that can be used effectively in hemodynamic studies.

PMID- 19181320
TI  - Synthesis by precipitation polymerisation of molecularly imprinted polymer
      microspheres for the selective extraction of carbamazepine and oxcarbazepine from
      human urine.
AB  - Two molecularly imprinted polymers (MIPs), in the physical form of well-defined
      polymer microspheres, were synthesised via precipitation polymerisation (PP)
      using an antiepileptic drug, carbamazepine (CBZ), as template molecule,
      methacrylic acid as functional monomer and either divinylbenzene 80 (DVB-80) or a
      mixture of DVB-80 and ethylene glycol dimethacrylate (EGDMA) as crosslinking
      agents. The MIP obtained using DVB-80 alone as crosslinking agent (MIP A) had a
      narrow particle size distribution (9.5+/-0.5 microm) and a well-developed
      permanent pore structure (specific surface area in the dry state=758 m(2)g(-1)),
      whereas when a mixture of DVB-80 and EGDMA (MIP B) were used as crosslinking
      agents, the polymer obtained had a broader particle size distribution (6.4+/-1.8
      microm) and a relatively low specific surface area (23 m(2)g(-1)). The molecular
      recognition character of both polymers was evaluated by means of LC and then a
      molecularly imprinted solid-phase extraction (MISPE) protocol; CBZ was recognised
      by both polymers, and useful cross-selectivity for oxcarbazepine (OCBZ), which is
      the main metabolite of CBZ, also observed. In a detailed bioanalytical study, MIP
      A was selected in preference to MIP B since MIP A enabled a high volume of sample
      to be extracted such that lower limits of detection were achievable using this
      polymer. High recoveries of CBZ and OCBZ were obtained in a MISPE protocol when
      50 m L of human urine spiked at 0.2 mg L(-1) were percolated through MIP A (90%
      and 83%, respectively).

PMID- 19181321
TI  - Analysis of advanced glycation endproducts in dairy products by isotope dilution
      liquid chromatography-electrospray tandem mass spectrometry. The particular case
      of carboxymethyllysine.
AB  - A fully validated multiple-transition recording isotope dilution liquid
      chromatography-electrospray tandem mass spectrometry (LC-MS/MS) method for the
      simultaneous quantitative determination of N(epsilon)-carboxymethyllysine (CML)
      and lysine in dairy products is described. Internal standards were [N-1',2'
      (13)C(2)]CML and [1,2,3,4,5,6-(13)C(6)-2,6-(15)N(2)]lysine, and the method was
      validated by evaluating the selectivity, linearity, precision (repeatability and
      reproducibility) and trueness, using both powder and liquid products. For liquid
      dairy products, the repeatability and reproducibility was 2.79% and 11.0%, while
      4.85% and 4.92% were determined for powder dairy products, respectively. The
      trueness of the method ranged from -9.6% to -3.6% for powder and from -0.99% to
      6.8% for liquid dairy products. The limit of detection for CML was estimated to
      be 8 ng CML per mg protein while the limit of quantification was 27 ng CML per mg
      protein. The method encompasses a proteolytic cleavage mediated by enzymatic
      digestion to reach a complete release of the amino acids prior to a sample
      cleanup based on solid phase extraction, and followed by LC-MS/MS analysis of CML
      and lysine residues. To ensure a suitable performance of the enzymatic digestion,
      CML measurements were compared to values obtained with an acid hydrolysis
      mediated proteolysis. Finally, the method was employed for the analysis of CML in
      various dairy products. The values compare well to the data available in the
      literature when similar methods were used, even if some discrepancies were
      observed upon comparison with the results obtained by other techniques such as
      enzyme-linked immunosorbent assay and GC-MS.

PMID- 19181322
TI  - Micellar selectivity triangle for classification of chemical selectivity in
      electrokinetic chromatography.
AB  - A novel micellar selectivity triangle (MST) is developed and used to characterize
      and classify the chemical selectivities of pseudo-phases in electrokinetic
      chromatography (EKC). The MST scheme is, in concept, similar to the widely known
      solvent selectivity triangle (SST) originally developed by Snyder. However, the
      MST is based on linear solvation energy relationships. Thus it incorporates the
      solvation characteristics of both the pseudo-phase and the bulk solvent; while
      the SST is basically for classification of pure solvents. The similarities and
      differences of these pseudo-phases are determined by the relative scales of
      hydrogen bond donating ability (X(b)), hydrogen bond accepting ability (X(a)) and
      dipolarity (X(s)). The MST scheme is used for characterization and classification
      of a wide range of pseudo-phases such as micelles, polymers, vesicles, liposomes,
      as well as mixed systems such as mixed micelles, mixed polymer-surfactants,
      organically modified pseudo-phases, etc. Over seventy pseudo-phases were examined
      and four clusters of pseudo-phases with different selectivity patterns are
      recognized that include pseudo-phases with strong hydrogen bond acidities (e.g.
      fluorinated micelles or micelles modified with fluorinated alcohols), strong
      hydrogen bond acceptor pseudo-phases (such as bile salts, liposomes,
      microemulsions, as well as biphasic octanol-water system), strong dipolar phase
      of a class of polymeric pseudo-phase, and pseudo-phases with intermediate
      hydrogen bonding and dipolarity [like sodium dodecyl sulfate (SDS) and its
      analogs as well as organically modified SDS]. The MST scheme is also useful in
      identifying pseudo-phases that closely resemble the selectivities of octanol
      water for determination of octanol-water partition coefficients by EKC.

PMID- 19181323
TI  - Selectivity patterns in micellar electrokinetic chromatography: characterization
      of fluorinated and aliphatic alcohol modifiers by micellar selectivity triangle.
AB  - The usefulness of the micellar selectivity triangle (MST) for prediction and
      interpretation of separation patterns in micellar electrokinetic chromatography
      (MEKC) separations is presented. In addition, we demonstrate the capability of
      controlling selectivity properties of micelles through addition of organic
      modifiers with known solvation properties as predicted by MST. The examples are
      modification of the hydrogen bond donor (HBD) micelle of lithium
      perfluorooctanesulfonate, the hydrogen bond acceptor (HBA) micelle of
      tetradecyltrimethylammonium bromide, and the sodium dodecyl sulfate micelles with
      intermediate hydrogen bonding properties with two hydrophobic organic modifiers.
      One is an aliphatic alcohol, n-pentanol that can act as both a HBA and a HBD; by
      contrast, the other organic modifier is a fluorinated alcohol,
      hexafluoroisopropanol that is a strong HBD modifier and would enhance the
      hydrogen bond donor strength of micelles. A test sample composed of 20 small
      organic solutes representing HBA, HBD, and non-hydrogen bond aromatic compounds
      was carefully selected. The trends in retention behavior of these compounds in
      different micelles are consistent with the selectivity patterns predicted by the
      MST scheme. To the best of our knowledge, this is the first report on the unique
      selectivity of fluorinated alcohols as modifiers in MEKC. These results
      demonstrate the usefulness of the MST scheme for identifying pseudo-phases with
      highly similar or different selectivities and can serve as a guide for judicious
      selection of modifiers to create pseudo-phases with desired selectivity behavior
      on a rational basis.

PMID- 19181324
TI  - Development of an improved method for the determination of polycyclic aromatic
      hydrocarbons in mainstream tobacco smoke.
AB  - A gas chromatograph/mass-selective detection (GC/MS) method has been developed
      and validated for the quantitation of 16 polycyclic aromatic hydrocarbons found
      in mainstream tobacco smoke condensate. The utilization of two types of solid
      phase extraction media combined with capillary column technology removed matrix
      interferences, afforded a significant reduction in analysis run time, and
      increased accuracy. Also, the addition of a chilled impinger was used to trap
      semi-volatile polycyclic aromatic hydrocarbons and to provide more accurate data.
      This was done without sacrificing the repeatability, reproducibility, and
      precision obtained in previously published methods. The development and
      validation studies discussed in this paper resulted in an improved, robust
      analytical method capable of increasing laboratory capacity and reducing sample
      reporting time.

PMID- 19181325
TI  - Effect of the conserved oligosaccharides of recombinant monoclonal antibodies on
      the separation by protein A and protein G chromatography.
AB  - Glycosylation of the conserved asparagine residue in CH2 domains of IgG molecules
      is an important post-translational modification. The presence of oligosaccharides
      is critical for structure, stability and biological function of IgG antibodies.
      Effect of the glycosylation states of recombinant monoclonal antibodies on
      protein A and protein G chromatography was evaluated. Antibodies lacking
      oligosaccharides eluted later from protein A and earlier from protein G columns
      than antibodies with oligosaccharides using a gradient of decreasing pH.
      Interestingly, different types of oligosaccharides also affected the elution of
      the antibodies. Antibodies with high mannose type oligosaccharides were enriched
      in later eluting fractions from protein A and earlier eluting fractions from
      protein G. While antibodies with more mature oligosaccharides, such as core
      fucosylated biantennary complex oligosaccharides with zero (Gal 0), one (Gal 1)
      or two (Gal 2) terminal galactoses, were enriched in earlier eluting fractions
      from protein A and in the later eluting fractions from protein G. However,
      analysis by enzyme-linked immunosorbent assay (ELISA) revealed that antibody
      binding affinity to protein A and protein G was not affected by the absence or
      presence of oligosaccharides. It was thus concluded that the elution difference
      of antibodies with or without oligosaccharides and antibodies with different
      types of oligosaccharides were due to differential structural changes around the
      CH2-CH3 domain interface under the low pH conditions used for protein A and
      protein G chromatography.

PMID- 19181326
TI  - Marangoni flow revisited.
AB  - A view of the Marangoni effect from the perspectives of all three possible
      interfaces as motion inducing agents is given. Arguments are made that it is
      required and sufficient that surface tension gradient at the substrate surface
      induce the flow while the liquid vapor surface tension gradient is unable to
      induce a flow on its own; that the flow is toward a lower interface potential at
      the wall liquid interface; and that this is an appropriate way of viewing the
      Marangoni effect is demonstrated with examples.

PMID- 19181327
TI  - Chasing drops: following escaper and pursuer drop couple system.
AB  - We study experimentally six different systems in which Marangoni flow is induced
      by two chemically different drops on a solid surface in air. In such systems one
      drop seems to chase away the other. We show that in all the systems studied, the
      Marangoni flow is induced at the solid-vapor interface as opposed to the air
      liquid interface. This is true even for the case of water drop and alcohol drop
      on a glass surface (which corresponds to the "tears of wine" classical case).
      Thus we explain the drop motion as a result of an interfacial tension gradient
      which takes place primarily at the air-surface region and less, if at all, at the
      two other interfaces in the problem: the liquid-substrate or liquid-air
      interfaces. Then we follow the motion of drops on surfaces and find that it is
      discontinuous, i.e. characterized by stops and jumps as in a stick slip
      mechanism. We explain this behavior by an increase in the Laplace pressure that
      creates a higher anchoring pinning effect at the front edge of the moving drop.
      The understanding of this process has implications for passively separating mixed
      liquids.

PMID- 19181328
TI  - New modified chitosan-based adsorbent for defluoridation of water.
AB  - In the present study, the metal-binding property of chitosan is used to
      incorporate titanium metal and applied as an adsorbent for fluoride adsorption.
      Titanium macrospheres (TM) were synthesized by a precipitation method and
      characterized by FTIR, SEM, and XRD. The Langmuir and Freundlich adsorption
      models were applied to describe the adsorption equilibrium and the adsorption
      capacities were calculated. Thermodynamic parameters of standard free energy
      change (DeltaG(o)), standard enthalpy change (DeltaH(o)), and standard entropy
      change (DeltaS(o)) were also calculated. The effects of various physico-chemical
      parameters such as pH, initial concentration, adsorbent dose, and the presence of
      coexisting anions were studied. The fluoride uptake was maximum at neutral pH 7
      and decreased in acidic and alkaline pH. The presence of coexisting anions has a
      negative effect on fluoride adsorption. TM was found to have very fast kinetics
      in the first 30 min and then the rate slowed down as equilibrium was approached.
      A comparison of fluoride removal in simulated and field water shows a high
      adsorption capacity in simulated water.

PMID- 19181329
TI  - Preparation of a hydroxyapatite film and its application in the removal and
      regeneration of aqueous cations.
AB  - Aqueous Pb(2+), Cd(2+), Co(2+), and Cu(2+) were continuously removed and
      regenerated using a bulk powder of calcium hydroxyapatite
      (Ca(10)(PO(4))(6)(OH)(2), CaHAp) and a glass plate coated with a thin film of
      CaHAp. Although use of CaHAp effectively removed aqueous Pb(2+) from the
      wastewater, lead cations immobilized on CaHAp could not be regenerated in an
      aqueous solution due to the formation of lead hydroxyapatite
      (Pb(10)(PO(4))(6)(OH)(2)), which is insoluble in water at acidic and neutral pH.
      In contrast, Co(2+) and Cu(2+) immobilized on CaHAp were easily regenerated in an
      aqueous solution by treatment with an acidic aqueous solution containing
      Ca(NO(3))(2), as previously reported for the CaHAp-Cd(2+) system. We found that
      the combination of the removal of the aqueous divalent cations by the CaHAp film
      and subsequent regeneration of the immobilized divalent cations from the film
      allowed for recycling of the film and for removal and regeneration of aqueous
      Cd(2+), Co(2+), and Cu(2+).

PMID- 19181330
TI  - Image-based models of cardiac structure with applications in arrhythmia and
      defibrillation studies.
AB  - The objective of this article is to present a set of methods for constructing
      realistic computational models of cardiac structure from high-resolution
      structural and diffusion tensor magnetic resonance images and to demonstrate the
      applicability of the models in simulation studies. The structural image is
      segmented to identify various regions such as normal myocardium, ventricles, and
      infarct. A finite element mesh is generated from the processed structural data,
      and fiber orientations are assigned to the elements. The Purkinje system, when
      visible, is modeled using linear elements that interconnect a set of manually
      identified points. The methods were applied to construct 2 different models; and
      2 simulation studies, which demonstrate the applicability of the models in the
      analysis of arrhythmia and defibrillation, were performed. The models represent
      cardiac structure with unprecedented detail for simulation studies.

PMID- 19181331
TI  - Parental overprotection predicts the development of functional somatic symptoms
      in young adolescents.
AB  - OBJECTIVE: To examine whether parental overprotection contributes to the
      development of functional somatic symptoms (FSS) in young adolescents. In
      addition, we aimed to study whether this potential effect of parental
      overprotection is mediated by parenting distress and/or moderated by the
      adolescent's sex. STUDY DESIGN: FSS were measured in 2230 adolescents (ages 10 to
      12 years from the Tracking Adolescents' Individual Lives Survey) by the Somatic
      Complaints subscale of the Youth Self Report at baseline and at follow-up 2 1/2
      years later. Parental overprotection as perceived by the child was assessed by
      means of the EMBU-C (Swedish acronym for my memories of upbringing-child
      version). Parents completed the Parenting Stress Index. Linear regression
      analyses were performed adjusted for FSS at baseline and sex. RESULTS: Parental
      overprotection was a predictor of the development of FSS in young adolescents
      (beta = 0.055, P < .01). Stratified analyses revealed that maternal
      overprotection was a predictor of the development of FSS in girls (beta = 0.085,
      P < .02), whereas paternal overprotection was a predictor of the development of
      FSS in boys (beta = 0.072, P < .01). A small (5.7%) but significant mediating
      effect of maternal parenting stress in the relationship between parental
      overprotection and FSS was found. CONCLUSIONS: Parental overprotection may play a
      role in the development of FSS in young adolescents.

PMID- 19181332
TI  - Preprinted order sets as a safety intervention in pediatric sedation.
AB  - OBJECTIVES: Implement preprinted packets for pediatric procedural sedations to
      increase documentation compliance and decrease medication ordering errors. STUDY
      DESIGN: Retrospective chart review of pediatric inpatients undergoing procedural
      sedation before and after implementation of a preprinted packet including an
      order set, consent form, and sedation monitoring form. Patient charts before and
      after the intervention were reviewed for completeness of medical documentation,
      correct medication dosages, and adverse events. Chi2 or Fisher exact test was
      used to determine preintervention vs postintervention differences. RESULTS: Forty
      two charts preintervention and 42 postintervention were reviewed. Documentation
      compliance increased on consent forms (P < .001), procedure notes (P = .113), and
      sedation monitoring forms (P = .003), while dating and timing of order forms
      decreased. Ordering of resuscitation equipment (P = .12), documentation of
      American Society of Anesthesiologists' (ASA) physical status classification (P <
      .001) and allergies (P < .001), and postsedation orders (P < .001) also
      increased. Medications ordered using unit/kg increased 43% (P < .05). Medication
      ordering errors for sedation agents decreased 64% (P < .001). Ordering of
      appropriate reversal agents increased 73% (P = .02). CONCLUSIONS: Implementing
      preprinted physician orders, consent forms, and prepared packets increased
      documentation compliance and ordering of reversal agents and resuscitation
      equipment. Medication dosage ordering errors decreased.

PMID- 19181333
TI  - Outcomes of siblings with classical galactosemia.
AB  - OBJECTIVES: To determine the long-term outcome of dietary intervention in
      siblings from 14 Irish families with classical galactosemia (McKusick 230400), an
      autosomal recessive disorder of carbohydrate metabolism and galactose-1-phosphate
      uridyltransferase (GALT) deficiency. STUDY DESIGN: Outcomes in siblings on
      dietary galactose restriction were studied to evaluate whether birth order (ie,
      time of commencement of diet) and compliance with lactose-restricted diet
      (galactose intake > or < 20 mg /day), assessed by dietary recall and biochemical
      monitoring of galactose-1-phosphate [Gal-1-P] and galactitol values, affected
      outcomes. The outcome variables assessed were IQ, speech, and language assessment
      scores, neurologic examination results, and magnetic resonance imaging (MRI) of
      the brain. RESULTS: There was a high incidence of complications in the overall
      group, particularly speech and language delay (77%) and low IQ (71%). There was
      no significant difference in outcome between earlier-treated and later-treated
      siblings or any correlation with mean Gal-1-P or galactitol values. In most
      cases, cerebral white matter disease was evident on MRI scanning, with evidence
      of progressive cerebellar degeneration seen in 2 highly compliant families.
      CONCLUSION: The subjects with a higher galactose intake did not exhibit an
      increased incidence of complications; conversely, those who were very compliant
      with dietary restrictions did not have more favorable outcomes.

PMID- 19181334
TI  - Regional differences in cerebral edema after traumatic brain injury identified by
      impedance analysis.
AB  - OBJECTIVE: Cerebral edema is a common and potentially devastating sequel of
      traumatic brain injury. We developed and validated a system capable of tissue
      impedance analysis, which was found to correlate with cerebral edema. METHODS:
      Constant sinusoidal current (50 microA), at frequencies from 500 to 5000 Hz, was
      applied across a bipolar electrode unit superficially placed in a rat brain after
      traumatic brain injury. Rats were randomized to three groups: severe controlled
      cortical injury (CCI), mild CCI, or sham injury. At 60 h post-CCI, cerebral
      voltage and phase angle were measured at each frequency at the site of injury, at
      the penumbral region, at the ipsilateral frontal region, and in the contralateral
      hemisphere. Impedance measurements were also obtained in vivo. The electrical
      properties of varied injuries and specified locations were compared using a
      repeated measures analysis of variance (RMANOVA), were correlated with regional
      tissue water percentage using regression analyses, and were combined to generate
      polar coordinates. RESULTS: The measured voltage was significantly different at
      the site of injury (P<0.0001), in the penumbra (P=0.002), and in the
      contralateral hemisphere (P=0.005) when severe, mild, and sham CCI rats were
      compared. Severely injured rats had statistically different voltage measurements
      when the various sites were compared (P=0.002). The ex vivo measurements
      correlated with in vivo measurements. Further, the impedance measurements
      correlated with measured tissue water percentage at the site of injury (R2=0.69;
      P<0.0001). The creation of a polar coordinate graph, incorporating voltage and
      phase angle measurements, enabled the identification of impedance areas unique to
      normal, mild edema, and severe edema measurements in the rat brain. CONCLUSIONS:
      Electrical measurements and tissue water percentages quantified regional and
      severity differences in rat brain edema after CCI. Impedance was inversely
      proportional to the tissue water percentage. Thus, impedance measurement can be
      used to quantify severity of cerebral edema in real time at specific sites.

PMID- 19181335
TI  - Hyperbaric oxygen as adjunctive therapy in experimental mediastinitis.
AB  - BACKGROUND: Mediastinitis is a dreaded complication of cardiac surgical
      procedures. The purpose of our study was to research the role of hyperbaric
      oxygen therapy (HBO) in the treatment of experimental mediastinitis and to
      investigate whether it potentiates the antibiotic effects of linezolid,
      teicoplanin, and vancomycin. METHODS: The study included nine groups; an
      uncontaminated and a contaminated untreated control groups, and seven
      contaminated groups that received HBO or systemic antibiotics with linezolid,
      vancomycin, or teicoplanin, or a combination therapy consisting of one of these
      antibiotics and HBO. There were six adult male Wistar rats in each group.
      Contaminated groups were inoculated with 0.5 mL 10(8) CFU/mL methicillin
      resistant Staphylococcus aureus in the mediastinal and in the sternal layers. The
      antibiotic treatment continued 7 d. Twelve hours later at the end of the
      treatment, the rats were sacrificed, a sternotomy was performed for each rat and
      tissue samples from the upper ends of the sternum were aseptically obtained and
      evaluated microbiologically. RESULTS: There was no difference between the
      therapeutic efficacy of linezolid, teicoplanin, or vancomycin (P>0.05). When the
      groups were analyzed separately, treatment with a combination of HBO and
      antibiotic therapy reduced the bacterial count in comparison with HBO or
      antibiotic treatment alone (P<0.05). The combination of teicoplanin or vancomycin
      and HBO, respectively, was not more effective in reducing the bacterial count in
      comparison with the combination of linezolid and HBO (P>0.05). CONCLUSIONS:
      Linezolid and teicoplanin therapy was found as effective as standard vancomycin
      therapy for methicillin resistant Staphylococcus aureus (MRSA) mediastinitis.
      Adjunctive HBO offered additional benefit to the antibiotic treatment of
      mediastinitis.

PMID- 19181336
TI  - 17Beta-estradiol activates adenosine A(2a) receptor after subarachnoid
      hemorrhage.
AB  - BACKGROUND: Our previous study showed that 17beta-estradiol (E2) and an adenosine
      A(2A) receptor (AR-A(2A)) agonist could attenuate subarachnoid hemorrhage (SAH)
      induced cerebral vasospasm via preventing the augmentation of iNOS expression and
      preserving the normal eNOS expression. This study tests the hypothesis that E2
      attenuates SAH-induced vasospasm and apoptosis by activating adenosine AR-A(2A)
      and extracellular signal-regulated kinase 1 and 2 (ERK1/2), and by altering
      antiapoptotic and proapoptotic protein expression (Bcl-2 and Bax, respectively).
      MATERIALS AND METHODS: The two-hemorrhage SAH model in rat was used. Animals were
      treated with E2 with or without a nonselective estrogen receptor (ER) antagonist
      (ICI182,780). The cross sectional areas of the basilar artery and terminal dUTP
      nick-end labeling (TUNEL) were used to determine the degree of vasospasm and
      apoptosis, respectively. The expressions of Bcl-2, Bax, AR-A(2A), and ERK1/2 in
      the cerebral cortex, hippocampus, and dentate gyrus were investigated. RESULTS:
      E2 significantly attenuated vasospasm. Seven days after the first SAH, TUNEL
      scores were significantly increased, and protein levels of AR-A(2A), ERK1/2, and
      Bcl-2 were significantly decreased in the dentate gyrus only but not in the
      cortex and hippocampus. These changes were reversed by E2 while ICI182,780
      abrogated the antiapoptotic and anti-spastic effects of E2. The expression of Bax
      did not change in the dentate gyrus after SAH with or without treatment.
      CONCLUSIONS: The down-regulated AR-A(2A) and ERK may play a role in vasospasm and
      apoptosis after SAH. The beneficial effect of E2 in the attenuating SAH-induced
      vasospasm and apoptosis may be due to an increased expression of AR-A(2A) and ERK
      via ER-dependent mechanisms. These data may support further investigation of E2
      in the treatment of SAH in humans.

PMID- 19181337
TI  - Preoperative early warning scores can predict in-hospital mortality and critical
      care admission following emergency surgery.
AB  - BACKGROUND: EWS is frequently used to monitor acute admissions requiring
      emergency surgery. This study examined preoperative early warning scoring (EWS)
      and its ability to predict mortality and critical care admission. Postoperative
      EWS was also evaluated as a predictor of mortality. METHODS: Preoperative EWS,
      age, physiologic and operative severity (POSSUM) scores, ASA grade, and serology
      were compared in 280 patients undergoing emergency surgery. RESULTS: Two hundred
      eighty patients were identified with a mortality of 15%. Among the physiological
      scoring systems, ASA grade and POSSUM scores were the best predictors of
      mortality (AUC values of 0.81). EWS, APACHE II, and age were the next best
      predictors (AUC values of 0.70). Postoperative APACHE II and EWS both predicted
      mortality. EWS on day 2 postoperatively was the best overall predictor of
      mortality of all the variables studied (AUC value of 0.83). Survival between
      patients with "improving or stable" EWS and those with "deteriorating or failing
      to improve" EWS was also found to be significantly different (P < 0.001). In
      addition, both EWS on admission and EWS 1 h preoperatively were found to predict
      critical care requirement postoperatively (AUC value of 0.78). CONCLUSIONS: EWS
      can predict the need for critical care admission and mortality following
      emergency surgery. In particular, the progression of EWS preoperatively, that is,
      whether scores improve or deteriorate, is a highly significant factor in
      predicting survival following emergency surgery. These findings support the use
      of EWS in monitoring the acute surgical patient.

PMID- 19181338
TI  - HO-1 activation can attenuate cardiomyocytic apoptosis via inhibition of NF
      kappaB and AP-1 translocation following cardiac global ischemia and reperfusion.
AB  - BACKGROUND: NF-kappaB and AP-1 play important roles in regulation of inflammatory
      responses that lead to cardiomyocytic injury following cardiopulmonary bypass
      (CPB) and cardiac global ischemia and reperfusion. It has been reported that heme
      oxygenase-1 (HO-1) can block those responses. Our aim was to determine whether HO
      1 activation could decrease myocardial ischemia-reperfusion injury with
      cardioplegia during CPB and attenuate apoptosis of cardiomyocytes. MATERIALS AND
      METHODS: Rabbits (10 in each group) were randomized to receive either bypass only
      (Group 1), CPB plus intravenous normal saline (Group 2), hemin (HO-1 inducer;
      Group 3), SnPP (HO-1 inhibitor; Group 4), or hemin + SnPP (Group 5) 2 d before
      CPB. In all groups except Group 1, cold (4 degrees C) antegrade intermittent
      crystalloid cardioplegia was delivered every 20 min for a total of 60 min of
      cardiac arrest, after CPB was established. Rabbits were weaned from CPB and
      reperfused for 4 h. Blood was sampled at various time points. The reperfused
      hearts were harvested for Western blotting and terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end labeling (TUNEL) experiments. RESULTS:
      The postoperative elevation of serum levels of IL-10, IL-6, and TNF-alpha were
      significantly decreased in Group 3, but HO-1 inhibitor abolished this effect
      (Group 4). Moreover in Group 3, the number of apoptotic cardiomyocytes, level of
      apoptosis-related activated fragments of caspase-3 and Akt, and level of nuclear
      NF-kappaB and AP-1 translocation were significantly decreased. CONCLUSIONS: HO-1
      activation can dampen the surge of inflammation-related cytokines during CPB and
      decrease the occurrence of cardiomyocytic apoptosis via inhibition of NF-kappaB
      and AP-1 translocation.

PMID- 19181339
TI  - DNA damaging effects of the dyes used in sentinel node biopsy: possible
      implications for clinical practice.
AB  - OBJECTIVE: This study investigates whether methylene blue (MB), patent blue V
      (PBV), and indigo carmine (IDC) commonly used in sentinel node biopsy cause DNA
      damage to breast epithelial cells in vitro. METHODS: MCF-7 and HB-2 cells were
      exposed for 5 minutes to the above dyes at the same concentrations used in
      clinical practice. Following exposure, the comet assay was performed to detect
      DNA damage. The enzyme, Fapy-DNA glycosylase (FpG) was incorporated to enable the
      detection of additional oxidative damage. RESULTS: Both PBV and MB stimulated DNA
      strand breaks in both MCF-7 and HB2 cell lines (P < 0.05). Levels were elevated
      over 3-fold (P < 0.05) in MCF-7 and HB2 cells treated with 2.5% PBV and 1% MB,
      compared with untreated control cells. In contrast, IDC did not stimulate DNA
      strand break damage at clinically relevant concentrations in either cell line.
      Addition of Fapy-DNA glycosylase enzyme also revealed significantly (P < 0.05)
      increased levels of oxidative DNA lesions (ODL) in MCF-7 cells treated with PBV
      (17.6% ODL) compared with control cells (5.9% ODL). CONCLUSIONS: This study
      shows, for the first time, that certain dyes (MB and PBV) commonly used in SLNB
      have genotoxic effects on breast cells at clinically relevant concentrations in
      vitro. In vivo studies are now warranted to assess and minimize DNA damage caused
      by these dyes during SLNB.

PMID- 19181340
TI  - Effects of dexmedetomidine on regulating endotoxin-induced up-regulation of
      inflammatory molecules in murine macrophages.
AB  - BACKGROUND: Effects of dexmedetomidine on regulating endotoxin-induced
      upregulation of inflammatory molecules were elucidated. METHODS: Murine
      macrophages (RAW264.7 cells) were treated with lipopolysaccharide (LPS, 100
      ng/mL), LPS plus dexmedetomidine (0.01, 0.1, 1, 10, or 100 microM), LPS plus
      dexmedetomidine plus yohimbine, or LPS plus dexmedetomidine plus idazoxan. The
      dosages of dexmedetomidine were chosen to correspond to 1, 10, 100, and 1000
      times of clinically relevant dosages (i.e., 0.01-0.1 microM). The levels of
      inducible nitric oxide synthase (iNOS)/nitric oxide (NO), cyclooxygenase-2 (COX
      2)/prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha), interleukin
      1beta (IL-1beta), IL-6, and IL-10 were measured. RESULTS: Dexmedetomidine at 0.01
      microM did not affect iNOS expression and NO production in activated macrophages.
      At 1 microM, dexmedetomidine significantly inhibited iNOS expression (up to 20.8%
      +/- 4.7%) and NO production (up to 26.2% +/- 6.8%). In contrast, dexmedetomidine
      at 100 microM significantly enhanced iNOS expression (up to 31.5% +/- 7.5%) and
      NO production (up to 34.9% +/- 5.6%). The effects of dexmedetomidine on COX-2
      expression and the production of PGE2, TNF-alpha, IL-1beta, IL-6, and IL-10
      paralleled the effects of dexmedetomidine on iNOS. Moreover, these effects were
      significantly reversed by both of the alpha2-adrenergic receptor antagonists,
      yohimbine, and idazoxan. CONCLUSIONS: Dexmedetomidine at clinically relevant
      dosages did not significantly affect the expression of inflammatory molecules in
      activated macrophages. In contrast, dexmedetomidine at dosages higher than
      clinically relevant ones posted small but significant biphasic effects
      (inhibiting, then enhancing) on regulating the expression of inflammatory
      molecules, possibly through the alpha2-adrenergic receptors. However, as the
      magnitude of changes was relatively small, these effects may not be clinically
      significant.

PMID- 19181341
TI  - Risk of adverse outcomes associated with blood transfusion after cardiac surgery
      depends on the amount of transfusion.
AB  - BACKGROUND: Blood product transfusion has been known for immunosuppressive
      effects, and over-transfusion is linked with adverse outcomes. In cardiac
      surgery, the risk of non-transfusion can be poor postoperative oxygen delivery
      and hemorrhage. We hypothesized that infectious complications, organ dysfunction,
      and mortality result after a given threshold of blood product transfusion is
      exceeded. METHODS: Retrospectively, a prospectively maintained institutional
      database was analyzed from April 1, 2004 through December 31, 2006. All patients
      undergoing coronary artery bypass and/or valve operations were evaluated for
      bivariate and multivariate associations of blood-product transfusion with
      postoperative complications and mortality. Additionally, risk factors associated
      with transfusion were assessed. Receiver operator characteristic (ROC) curves
      analyses were employed to determine transfusion thresholds associated with
      complications. RESULTS: During the study period, 741 patients met inclusion
      criteria. Fifty-four percent received postoperative blood-product transfusions.
      Previous cardiac intervention, renal dysfunction, stroke, and immunosuppression
      were some of the risks associated with transfusion (P < 0.05). Specific
      complications independently (P < 0.05) associated with total blood product
      transfusion identified from the multivariate analysis were infectious,
      neurologic, organ dysfunction, cardiac, and death. From ROC curve analyses, 5.5
      units of total blood product transfusion was the inflection point for infectious
      complications (sensitivity 73%, specificity 64%) and organ dysfunction
      (sensitivity 73%, specificity 64%). For mortality, the inflection point was a
      transfusion of 7.5 units of total blood-products (sensitivity 73%, specificity
      71%). CONCLUSION: Bloodless cardiac surgery is associated with a decreased
      morbidity and mortality. Limiting transfusion is advisable. Transfusion of less
      than 5.5 units of total blood-products may not have deleterious effects on
      outcomes.

PMID- 19181342
TI  - Choice of hemostatic agent influences adhesion formation in a rat cecal adhesion
      model.
AB  - INTRODUCTION: Hemostatic agents are frequently used during abdominal surgery and
      some are linked to adhesion formation. We sought to evaluate the impact of
      several commonly used hemostatic agents on adhesion formation in a rat peritoneal
      model. METHODS: In our study, Wister outbred rats underwent laparotomy and
      excision of a portion of their peritoneum to initiate adhesion formation process.
      One of six different hemostatic agents, namely, activated starch microspheres
      (Arista AH; Medafor Inc., Minneapolis, MN), glutaraldehyde activated collagen
      (BioGlue; Cryolife Inc., Kennesaw, GA), thrombin coated collagen microspheres
      (FloSeal; Baxter Inc., Deerfield, IL), thrombin activated fibrin polymer
      (Tisseel, Baxter), polyethylene glycol polymer (CoSeal, Baxter), or oxidized
      cellulose (Surgicel; Ethicon Inc., Somerville, NJ), was placed in the area of
      peritoneal defect. All animals were sacrificed on post-op day 7 and strength and
      extent of adhesion formation was determined. Histopathological examination of rat
      caecum was also performed. RESULTS: Arista and CoSeal showed significantly lower
      adhesion formation than controls (P < 0.05). Higher adhesion scores were seen in
      BioGlue (P < 0.05) treated rats. Additionally, histopathologic examination showed
      that BioGlue caused statistically more inflammation and necrosis than controls (P
      < 0.05). Total adhesion score increased with residual amount of agent present at
      7 d. CONCLUSIONS: Use of Arista and CoSeal may help in reducing peritoneal
      adhesions after intra-abdominal surgeries. Furthermore, there appears to be a
      relationship between the creation of inflammation and necrosis in tissues and the
      eventual formation of adhesions. This could aid in improving the design of these
      agents in the future.

PMID- 19181343
TI  - The effects of different nutritional measurements on delayed wound healing after
      hip fracture in the elderly.
AB  - BACKGROUND: It has been well recognized that malnutrition causes wounds to heal
      inadequately and incompletely. Malnutrition is often observed in the elderly, and
      it appears to be more severe in patients with hip fracture than in the general
      aging population. Few prospective studies give a detailed account of the
      identification and classification of nutritional status in the elderly. The
      objective of this study was to evaluate the effects of different nutritional
      measurements on wound healing status after hip fracture in the elderly. METHODS:
      From September 2002 to December 2007, 207 hip fracture patients older than 60 y
      treated surgically were reviewed for preoperative nutritional status. There were
      81 males and 126 females with an average age of 75.93 y (62-91 y); 131 cases with
      femoral neck fractures, 76 cases with intertrochanteric fractures. Parameters
      indicative of nutritional status (serum albumin, serum transferrin, serum pre
      albumin, and total lymphocyte count levels) at the time of admission were
      assessed, along with anthropometric measurements, Rainey MacDonald nutritional
      index, and MNA tool. Suture removal was performed on postoperative day 14.
      RESULTS: Delayed wound healing complicated 46 (22.2%) of the 207 cases. The
      preoperative serum transferring total lymphocyte count levels, MNA total score,
      and Rainey MacDonald nutritional index were significantly lower for patients who
      subsequently had delayed wound healing. When all variables were subjected to
      multivariate analysis, only total lymphocyte count levels and MNA total score
      showed significant value in predicting which patients would have delayed wound
      healing. Through prophylactic antibiotics and adherence to strict aseptic
      precautions, on follow-up, wound healing was normal in all patients. CONCLUSIONS:
      Patients at risk for delayed wound healing problems after hip fracture can be
      identified using relatively inexpensive laboratory test such as TLC and MNA tool.
      The clinician must be aware of the risk values of both measurements. We believe
      this information is particularly important before planning procedures of hip
      fractures in the elderly.

PMID- 19181344
TI  - Percutaneous US-guided implantation of Vx-2 carcinoma into rabbit liver: a
      comparison with open surgical method.
AB  - PURPOSE: To evaluate technical feasibility and experimental usefulness of
      percutaneous US-guided implantation of Vx-2 carcinoma in rabbit liver. MATERIALS
      AND METHODS: Forty-eight New Zealand White male rabbits were used. Solid tumor
      mass of Vx-2 carcinoma was harvested from carrier rabbit, and minced tumor cells
      were implanted. Twenty-four rabbits underwent percutaneous US-guided tumor
      implantation, and the same number of rabbits underwent open laparotomy tumor
      implantation. Tested parameters included technical success, procedural time,
      amount of anesthesia, recovery time, complications, tumor size, and regional
      tumor seeding. RESULTS: A new percutaneous US-guided implantation was technically
      feasible in all rabbits. Evaluation parameters showed that the percutaneous US
      guided implantation method is less invasive than the open laparotomy method.
      Targeting rate for left lateral lobe of implantation site was comparable in both
      methods (91.7% of percutaneous US-guided; 95.8% in open laparotomy). The success
      rate of tumor growth in the liver was 100% in both groups. However, in the group
      with US-guidance, tumor seeding developed more frequently in five of 24 rabbits
      (20.8%) than in open laparotomy group (2/24, 8.3%). Five rabbits had
      thoracoabdominal wall needle tract seeding, and two rabbits had tumor seeding at
      both thoracoabdominal wall and intraperitoneal space. CONCLUSIONS: Percutaneous
      US-guided implantation of Vx-2 carcinoma in rabbit liver is a less invasive
      alternative to open laparotomy, achieving equally successful tumor growth in the
      liver. Although percutaneous US-guidance implantation method may not be
      considered for long-term survival study design because of the possibility of
      tumor seeding, it can be considered for nonsurvival study design.

PMID- 19181345
TI  - The prognostic significance of cerebrospinal fluid in multiple sclerosis.
AB  - BACKGROUND: Multiple Sclerosis (MS) patients lacking CSF oligoclonal bands are
      purported to have a milder course of disease. We reviewed the natural history of
      oligoclonal band (OCB) - negative (OCB-) compared to OCB positive (OCB+)
      patients. METHOD: A retrospective study of 451 MS patients. RESULTS: Only 48/451
      patients (10.6%) were CSF OCB-. The mean age at onset was 37.1+/-8.8 years with
      female:male ratio=2. First CNS location presentation was less well defined in OCB
      vs. OCB+ patients with significantly more supratentorial presentation. The
      clinical course of OCB- vs OCB+ was somewhat different; 22.9 vs 15.1% PPMS; 18.8
      vs 12.4% SPMS; and 56.3 vs 71% RRMS, respectively. There were significantly fewer
      WBC, less IgG and a lower IgG index in OCB- cases. Fewer OCB- cases fulfilled
      McDonald MRI criteria. There were no discernable differences in disease severity
      between the two groups as determined by the EDSS, progression index, MSSS, number
      of relapses or annualized relapse rate. CONCLUSION: The presence of OCB
      correlates better with other indications of acute inflammatory MS, especially an
      RR course. This study suggests that the simple lack of OCB positivity does not
      necessarily insure a more benign disease course.

PMID- 19181346
TI  - Spinal cord involvement in Balo's concentric sclerosis.
AB  - We present a patient with a history of myelitis, who had a steroid refractory
      attack of CNS inflammatory demyelinating disease that developed into cerebral
      concentric sclerosis of Balo after plasma exchange. The acute inflammatory
      disease involved the spinal cord, a phenomenon rarely demonstrated. This patient
      fulfilled the McDonald criteria for multiple sclerosis. Plasmapheresis did not
      have a beneficial effect, but the patient stabilised at high EDSS after treatment
      with mitoxantron.

PMID- 19181349
TI  - Urethral stricture is now an open surgical disease.

PMID- 19181347
TI  - White matter hemodynamic abnormalities precede sub-cortical gray matter changes
      in multiple sclerosis.
AB  - BACKGROUND: Hypoperfusion has been reported in lesions, normal-appearing white
      (NAWM) and gray matter (NAGM) of patients with clinically definite multiple
      sclerosis (MS) by using perfusion MRI. However, it is still unknown how early
      such changes in perfusion occur. The aim of our study was to assess the presence
      of hemodynamic changes in the NAWM and subcortical NAGM of patients with
      clinically isolated syndrome (CIS) in comparison to healthy controls and to
      patients with early relapsing-remitting (RR) MS. METHODS: Absolute cerebral blood
      flow (CBF), blood volume (CBV) and mean transit time (MTT) were measured in the
      periventricular and frontal NAWM, thalamus and putamen nuclei of 12 patients with
      CIS, 12 with early RR-MS and 12 healthy controls using dynamic susceptibility
      contrast enhanced (DSC) T2*-weighted MRI. RESULTS: Compared to controls, CBF was
      significantly decreased in the periventricular NAWM of CIS patients and in the
      periventricular NAWM and putamen of RR-MS patients. Compared to CIS, RR-MS
      patients showed a significant CBF decrease in the putamen. CONCLUSIONS: CBF was
      decreased in the NAWM of both CIS and RR-MS patients and in the subcortical NAGM
      of RR-MS patients suggesting a continuum of tissue perfusion decreases beginning
      in white matter and spreading to gray matter, as the disease progresses.

PMID- 19181350
TI  - Polycyclic aromatic hydrocarbons in coastal sediments of southwest Taiwan: an
      appraisal of diagnostic ratios in source recognition.
AB  - Fifty-seven surface sediment samples were collected from the coast of southwest
      Taiwan and analyzed for polycyclic aromatic hydrocarbons (PAHs). Concentrations
      of total PAHs (28 PAH compounds) ranged from 15 to 907 ng g(-1) dry weight.
      Diagnostic ratios showed that PAHs in the sediments of the Gaoping estuary were
      predominantly of petroleum origin, whereas sediments from the Kaohsiung coast
      contained principally combustion-derived PAHs. Principal component analysis
      indicated that emissions from automobiles and coal burning were the main sources
      of combustion-derived PAHs. The relatively high ratios of perylene/penta-aromatic
      PAH isomers in sediments from the Tainan coast and some off-shore stations on the
      Kaohsiung coast suggest a significant diagenetic PAH contribution. The study
      shows that certain diagnostic ratios are useful and sensitive in delineating the
      distribution of PAHs from specific sources in southwest Taiwan. The
      phenanthrene/anthracene ratio is a better indicator than the
      methylphenanthrenes/phenanthrene ratio for tracing petrogenic PAHs, and the
      benzo(a)anthracene/chrysene and indeno(1,2,3-c,d)pyrene/benzo(g,h,i)perylene
      ratios are more specific than the benzo(a)pyrene/benzo(e)pyrene and
      benzo(b)fluoranthcene/benzo(k)fluoranthcene ratios in distinguishing PAHs from
      various pyrogenic sources.

PMID- 19181351
TI  - Patterns of real-time occupational ultraviolet radiation exposure among a sample
      of outdoor workers in New Zealand.
AB  - OBJECTIVES: Exposure to solar ultraviolet radiation (UVR) is an occupational
      health and safety issue for outdoor workers since excessive exposure is
      associated with negative health outcomes, including eye conditions and skin
      cancers. The objective of this research was to describe the pattern of UVR
      exposure experienced by outdoor workers from selected occupations in New Zealand
      in order to identify the impact of behaviour and work conditions on exposure.
      STUDY DESIGN: This paper reports on the occupational UVR exposure arm of a dual
      arm cross-sectional study that also examined workers' sun protection practices.
      METHODS: For five consecutive working days in January-March 2007, electronic
      dosimeters were used to record the time-stamped UVR exposure of a sample of 77
      outdoor workers from three occupations (building, horticulture and roading) in
      Central Otago, New Zealand. RESULTS: The geometric mean total daily UVR exposure
      (between 1100 and 1600 h) was 5.32 standard erythemal doses (SED; 95% reference
      range 0.28-19.97 SED). The geometric mean total daily UVR exposure as a
      percentage of the total daily ambient UVR was 20.5% (95% confidence interval 1.4
      83.0%). Personal UVR exposure dipped between 1200 h and 1300 h--the same time
      that ambient UVR peaked--indicating the effect of shade seeking over the lunch
      period. Personal UVR exposure peaked between 1400 h and 1500 h, alongside
      decreasing ambient UVR levels, suggesting the influence of behavioural rather
      than climatic factors. The difference in workers' exposure between 1200 h and
      1300 h, and 1400 h and 1500 h was statistically significant for both measured
      personal exposure (P < 0.005) and exposure calculated as a percentage of
      concurrent available ambient UVR (P < 0.005). CONCLUSIONS: All the workers in
      this study recorded mean daily UVR exposure in excess of the current recommended
      occupational exposure limits. Only a minority of workers sought shade during
      their lunch break; most remained in highly exposed conditions. There is no
      evidence that work tasks which involve substantial sun exposure are being
      scheduled outside the high UVR period.

PMID- 19181352
TI  - Bovine fasciolosis: prevalence, effects of treatment on productivity and cost
      benefit analysis in five districts of Punjab, Pakistan.
AB  - The present study reports the prevalence, effects of treatment and cost benefit
      analysis of bovine fasciolosis in five districts of Punjab Province viz Sargodha,
      Jhang, Muzaffargarh, Lodhran and Layyah. From each of the five districts, 80
      animals were selected and fortnightly screened through standard coprological
      procedures for a period of one year for the presence of eggs of Fasciola species.
      Of 4800 faecal samples analyzed, 1222 (25.46%) were found positive for
      fasciolosis. The occurrence of Fasciola (F.) gigantica (22.40%) was higher
      (P<0.05) than F. hepatica (3.06%). Highest month-wise prevalence (P<0.05) of
      fasciolosis was found in winter (39.08%) followed in decreasing order by spring
      (29.50%), autumn (20.33%) and summer (12.92%). District-wise prevalence of
      fasciolosis was highest (P<0.05) in Sargodha (40.31%) and lowest in Layyah
      (11.77%) while other districts were having intermediate values of prevalence of
      fasciolosis. Species-wise prevalence of fasciolosis was found higher (P<0.05) in
      buffaloes (30.50%) as compared to cattle (20.42%). However, there were no age and
      sex-related differences (P>0.05) in prevalence of fasciolosis. A strong positive
      association of grazing (OR=1.81), mixed farming of small and large ruminants
      (OR=1.39), stagnant pond bathing (OR=2.24) and river/canal bathing (OR=2.06) was
      found with the prevalence of fasciolosis as compared to stall feeding, separate
      farming of small and large ruminants and rivers/canal/tap water bathing,
      respectively. Post-treatment average milk increase of 0.62 L per animal per day
      with 0.35% higher fat was observed in fasciolicide-treated animals with the cost
      benefit ratio of 3.9. The results provided significant data on the epidemiology
      of five districts of Punjab province which may be helpful for the planners and
      small holder dairy farmers for control of fasciolosis in the study districts.

PMID- 19181353
TI  - Cytokine expression in colostrum-deprived pigs immunized and challenged with
      Haemophilus parasuis.
AB  - The expression of several cytokines in spleen, pharyngeal lymph nodes, lung and
      brain after different immunization procedures and a challenge with 5 x 10(9) CFU
      of Haemophilus parasuis was compared. Five groups of colostrum-deprived pigs were
      used: vaccinated with (I) a bacterin, (II) an outer-membrane-protein-vaccine,
      (III) a recombinant transferring-binding protein B, (IV) exposed to a total dose
      of 10(5) CFU, and (V) not previously immunized. All pigs in groups III and V
      died, while all animals in group I, most of group IV and half of group II
      survived until the end of the experiment. IL-1alpha was found in significantly
      higher levels (p<0.05) in spleen, lymph nodes and brain of dead pigs, which could
      be explained by the major severity of lesions in these animals. However, IL-4, IL
      10, TNF-alpha and IFN-gamma were expressed in significantly higher levels by
      survivors (for all the four cytokines in lymph nodes; for IL-4, IL-10 and TNF
      alpha in spleen; for IL-4, TNF-alpha and IFN-gamma in lung, and only for TNF
      alpha in brain), thus suggesting a role of these four cytokines in the adaptive
      response, which might contribute to protection against H. parasuis infection.

PMID- 19181354
TI  - Blood acid-base and plasma electrolyte values in healthy ostriches: the effect of
      age and sex.
AB  - The effect of age and sex on blood acid-base and plasma electrolyte values was
      determined in venous blood samples from 45 clinically healthy ostriches (Struthio
      camelus) from 26 days to 6 years of age. Animals were divided by age into four
      groups and the group of adults was divided by sex into two subgroups. Blood
      samples were collected without sedation. There was a significant (P<0.05) age
      difference in blood values of base excess (BE), plasma HCO(3)(-), total CO(2)
      (TCO(2)), Na(+), K(+), Cl(-) and anion gap (AG). The highest plasma
      concentrations of Na(+), Cl(-) and value of AG were found in adult ostriches with
      a steady decrease to chicks. A significant (P<0.05) sex difference in adult
      animals with higher blood pH, lower blood values of pCO(2), BE, plasma
      concentrations of HCO(3)(-), TCO(2) and K(+) was found in females. We concluded
      that blood acid-base values and plasma electrolyte concentrations in ostriches
      are affected by age and sex.

PMID- 19181355
TI  - Expression of tracheal antimicrobial peptide in bovine mammary epithelial cells.
AB  - The production of antimicrobial peptides is an important key of innate immunity.
      Tracheal antimicrobial peptide (TAP) expression has been reported in bovine
      tracheal epithelial cells and it can be modulated by bacterial infection or
      bacterial components. In mammary gland TAP expression has been reported, but the
      cell type that produces it is unknown. The objective of this work was to evaluate
      if bovine mammary epithelial cells (bMEC) express TAP mRNA, and evaluate the
      regulation of its expression in response to Staphylococcus aureus infection,
      bovine prolactin (bPRL) or acetyl salicylic acid (ASA). By retrotranscription and
      PCR, we demonstrated that bMEC express TAP mRNA. bMEC infected with live S.
      aureus down-regulates TAP expression, whereas the challenge with gentamicin
      killed S. aureus up-regulates it. Also, bPRL do not significantly modify TAP
      expression, but in the presence of 5 mM ASA it was down-regulated, suggesting
      that nuclear factor kappaB (NF-kappaB) pathway can be involved in its regulation.

PMID- 19181356
TI  - [Answer to M. Champy's letter].

PMID- 19181357
TI  - Filaria control and elimination: diagnostic, monitoring and surveillance needs.
AB  - Gold standard diagnosis using blood films or skin snips has dimished relevance as
      mass drug distribution programmes for control of filaria infections expand. The
      view of 'diagnosis' and its relevance at the individual level has changed, as it
      has been recognised that the spectrum of programmatic processes (mapping, mass
      drug interventions, monitoring and evaluation, and surveillance) require
      different approaches as different questions are asked at each stage. The
      feasibility and relevance of skin biopsy or blood film examination is challenged
      when mass drug distribution seeks to treat all eligibles in communities. The need
      to expand programmes rapidly by identifying the highest risk communities has seen
      the development of rapid assessment methods, such as rapid epidemiological
      mapping of onchocerciasis (REMO) and rapid epidemiological assessment (REA) for
      onchocerciasis, immunochromatographic test (ICT)-based mapping for lymphatic
      filariasis (LF), and Rapid Assessment Procedure for Loiasis (RAPLOA) for Loa, to
      reduce the risk of serious adverse events and to guide projects in high-risk
      communities. As programmes reduce the prevalence through mass drug distribution,
      more sensitive techniques are required to define endpoints, for LF in particular
      where the programmatic goal is elimination; for onchocerciasis, sensitive
      surveillance tools are required particularly in those areas where such risks of
      recrudescence are high. Whilst much progress has been made in the development and
      deployment of rapid methods, there are still specific needs for antigen detection
      in onchocerciasis, whilst standardisation of a panel of tools for LF will allow
      the definition of endpoint parameters so that countries can decide when mass drug
      administration (MDA) can be stopped and have a sensitive post-MDA surveillance
      system.

PMID- 19181359
TI  - cis preferential replication of Lettuce infectious yellows virus (LIYV) RNA 1:
      the initial step in the asynchronous replication of the LIYV genomic RNAs.
AB  - A series of Lettuce infectious yellows virus (LIYV) RNA 1 mutants was created to
      evaluate their ability to replicate in tobacco protoplasts. Mutants DeltaEcoRI,
      DeltaE-LINK, and Delta1B, having deletions in open reading frames (ORFs) 1A and
      1B, did not replicate when individually inoculated to protoplasts or when co
      inoculated with wild-type RNA1 as a helper virus. A fragment of the green
      fluorescent protein (GFP) gene was inserted into the RNA 1 ORF 2 (P34) in order
      to provide a unique sequence tag. This mutant, P34-GFP TAG, was capable of
      independent replication in protoplasts. Mutants derived from P34-GFP TAG having
      frameshift mutations in the ORF 1A or 1B were unable to replicate in protoplasts
      alone or in trans when co-inoculated with wild-type RNA1 as a helper virus. Taken
      together, these data strongly suggest that LIYV RNA 1 replication is cis
      preferential.

PMID- 19181360
TI  - Bioavailability and detoxification of cationics: I. Algal toxicity of
      alkyltrimethyl ammonium salts in the presence of suspended sediment and humic
      acid.
AB  - We investigated the role of sorption in reducing bioavailability and consequently
      the measured toxicity of monoalkyl trimethyl ammonium salts (MAQ) under
      environmental conditions. The observed toxicity of MAQ in the presence of various
      types of sorbents was tested on algae. Decreased toxicity was found in the
      presence of all particulate sorbents tested, i.e. montmorillonite, silica,
      different sediments and for dissolved humic acid. Silica had a minor effect on
      the observed toxicity, whereas the clay mineral montmorillonite detoxified very
      effectively. The detoxification by several real-world sediments being mixtures of
      sand and clay was in-between silica and montmorillonite. Humic acid detoxified
      most effectively on weight basis. Polynomial relationships ('QSARs') were
      established for algal toxicity of MAQ in the presence of montmorillonite, silica
      and humic acid with carbon chain length as descriptor. Freundlich sorption
      isotherms for MAQ C16 for a clay sediment, montmorillonite, silica and for algae
      confirmed their relative detoxification in toxicity tests. Humic acid
      significantly reduced bioavailability and observed toxicity of quaternary
      ammonium salts. Sorption of positively charged amines to suspended sediment is
      effectively controlled by its silt/clay fraction, not by the organic fraction.
      Purchased defined quality montmorillonite can serve as model sorbent in standard
      tests mimicking the clay fraction of natural suspended matter. It enables to
      study the effect of bioavailability on toxicity in a standardised way. The QSARs
      developed for ecotoxicity of MAQ in the presence of suspended matter and humic
      acid enable quantitative incorporation of bioavailability in effect assessment.
      This increases realism in risk assessments of these fatty amine derivatives.

PMID- 19181358
TI  - Viral regulatory region effects on vertical transmission of polyomavirus SV40 in
      hamsters.
AB  - Viral strain differences influence the oncogenic potential of polyomavirus simian
      virus 40 (SV40). We hypothesized that viral strain differences might also affect
      vertical transmission of SV40 in susceptible hosts. Pregnant Syrian golden
      hamsters were inoculated intraperitoneally with 10(7) plaque-forming units of
      SV40 and offspring were sacrificed post-delivery (1-21 days, 6 months). Organ
      extracts were analyzed for SV40 DNA by polymerase chain reaction assay.
      Transmission of SV40 from mother to offspring was detected in over half of
      litters. Most placentas were virus-positive. Mothers inoculated with SV40 strains
      containing complex regulatory regions transmitted virus more frequently than
      those infected with simple enhancer viruses (p<0.001). Virus was detected more
      often in progeny brain than in spleen (p<0.05). Several progeny were virus
      positive at 6 months of age, suggesting viral persistence. Maternal animals
      retained virus in several tissues through day 21 and developed T-antigen
      antibodies. These results indicate that SV40 replicates in hamsters, vertical
      transmission of SV40 can occur, and the viral regulatory region influences
      transmission.

PMID- 19181361
TI  - Potential applications of surface active compounds by Gordonia sp. strain BS29 in
      soil remediation technologies.
AB  - A wide range of structurally different surface active compounds (SACs) is
      synthesised by many prokaryotic and eukaryotic microorganisms. Due to their
      properties, microbial SACs have been exploited in environmental remediation
      techniques. From a diesel-contaminated soil, we isolated the Gordonia sp. strain
      BS29 which extensively grows on aliphatic hydrocarbons and produces two different
      types of SACs: extracellular bioemulsans and cell-bound biosurfactants. The aim
      of this work was to evaluate the potential applications of the strain BS29 and
      its SACs in the following environmental technologies: bioremediation of soils
      contaminated by aliphatic and aromatic hydrocarbons, and washing of soils
      contaminated by crude oil, polycyclic aromatic hydrocarbons (PAHs) and heavy
      metals. Microcosm bioremediation experiments were carried out with soils
      contaminated by aliphatic hydrocarbons or PAHs, while batch soil washing
      experiments were carried out with soils contaminated by crude oil, PAHs or heavy
      metals. Bioremediation results showed that the BS29 bioemulsans are able to
      slightly enhance the biodegradation of recalcitrant branched hydrocarbons. On the
      other hand, we obtained the best results in soil washing of hydrocarbons. The
      BS29 bioemulsans effectively remove crude oil and PAHs from soil. Particularly,
      crude oil removal by BS29 bioemulsans is comparable to the rhamnolipid one in the
      same experimental conditions showing that the BS29 bioemulsans are promising
      washing agents for remediation of hydrocarbon-contaminated soils.

PMID- 19181362
TI  - Surface-catalysed reactions on pollutant-removing building products for indoor
      use.
AB  - In order to evaluate the potential for emission of secondary reaction products
      from building materials designed to remove pollutants from indoor air, four
      samples of ceiling tiles--three commercially available and one custom-made--were
      investigated in chamber experiments. The chambers were irradiated with artificial
      light simulating indoor conditions and formaldehyde as well as several VOCs (2
      butanone, n-butanol, toluene, hexanal, n- butylacetate, 2-butoxyethanol, alpha
      pinene, benzaldehyde, n-decane, limonene and 1,2-dichlorobenzene) were added.
      Depending on the individual substrate-substance combination, it was possible to
      identify secondary emissions, e.g. formaldehyde, furfural, acetophenone, n
      butylbutyrate, n-butyl-i-butyrate, n-butylpropionate, 4-heptanone, acetic acid, i
      butyraldehyde and crotonaldehyde. These were generated by cleavage, hydrolysis,
      rearrangement or radical reactions. Some of these reactions also occurred with
      samples not containing photocatalysts. All these secondary emissions have to be
      taken seriously into account when evaluating the performance of materials
      designed to remove pollutants from indoor air, as they can prove detrimental to
      human health.

PMID- 19181363
TI  - Induction of oxidative stress biomarkers associated with heavy metal stress in
      Fontinalis antipyretica Hedw.
AB  - The aquatic bryophyte Fontinalis antipyretica Hedw. was exposed to different
      heavy metals (Cd, Cu, Pb, Zn) at 0, 0.1, 1, 10, 100 and 1000muM concentrations.
      Lipid peroxidation and anti-oxidative responses in apices were evaluated after 2
      and 7 days of exposure. Most treated plants showed increased levels of lipid
      peroxidation and enzyme activities (superoxide dismutase (SOD), catalase (CAT),
      glutathione reductase (GRD), ascorbate (APX) and guaiacol (GPX) peroxidases,
      compared to control (untreated) plants. Most of our results suggest that plants
      possess antioxidant enzymes which operates either unspecifically (SOD and APX) or
      depending on the nature of the contamination (CAT, GPX, GRD). However, for the
      highest metal concentration tested, these cellular defence systems seemed
      overwhelmed since MDA levels increased significantly. These results confirm the
      important role of antioxidant defences in the mechanisms of plant-resistance to
      heavy metal stress. Moreover, two types of concentration-response trends were
      identified: clear monotonous relationships were often found for SOD and MDA while
      bell-shaped trends were usually observed for APX, GPX and GRD. These tendencies
      are discussed with emphasis on possible use of these responses as plant
      biomarkers for freshwater biomonitoring surveys.

PMID- 19181364
TI  - Influence of an estuary dam on the dynamics of bisphenol A and alkylphenols.
AB  - The present study investigated the dynamics of xenoestrogenic compounds,
      bisphenol A (BPA) and alkylphenols, in the Nagara River, which has an estuary
      dam. The results were compared with the neighbouring Ibi River, which does not
      have such a dam. The mean concentrations of BPA in the Nagara River ranged from
      0.06 to 0.33 microg/L compared with 0.25 microg/L in the Ibi River. Although
      these results are similar to those for rivers in urban areas, the concentrations
      in the bottom water layer (up to 15 cm from sediment surface) in the Nagara River
      were significantly higher, with a maximum magnification (bottom water
      layer/surface water) of more than 650. The main portions of BPA in the bottom
      water layer in the Nagara River were in a soluble state. Moreover, there was a
      high correlation (R(2)=0.78) between the BPA content in the bottom sediment and
      BPA concentration in the bottom water layer. BPA and 4-nonylphenol (4NP) content
      was higher in the Nagara River sediment than in the Ibi River sediment. However,
      there was no discrepancy between 4NP concentrations in the surface water and the
      bottom water layer. These phenolic compounds were highly protected from aerobic
      degradation in the bottom sediment in the reservoir of the dam and the observed
      discrepancy depended on the differences in solubility of the compounds. The
      results show that an estuary dam facilitates accumulation and storage of
      xenoestrogenic compounds.

PMID- 19181365
TI  - Removal of dioxins and dioxin-like PCBs from fish oil by countercurrent
      supercritical CO2 extraction and activated carbon treatment.
AB  - It has been known that fish oils are prone to contamination by polychlorinated
      dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like
      polychlorinated biphenyls (DL-PCBs). In this study, the removal of contaminants
      from fish oil by countercurrent supercritical CO(2) extraction (CC-SCE) and
      activated carbon treatment was investigated. Fish oil was treated by CC-SCE at 70
      degrees C and 30MPa and with a CO(2)/oil ratio of 72; this resulted in a 93%
      reduction in the sum of PCDDs, PCDFs and DL-PCBs concentration level by and 85%
      reduction in toxic equivalency (TEQ). CC-SCE uses 40% less CO(2) and yields 30%
      more refined oil than semi-batch-type processes. Subsequent treatment by
      activated carbon reduced the concentration level by 94% and TEQ by 93%. CC-SCE is
      effective for the removal of DL-PCBs, whereas activated carbon treatment is
      effective for the removal of PCDD/Fs. These results reveal that the combination
      of CC-SCE and activated carbon treatment is applicable to the removal of PCDD/Fs
      and DL-PCBs from fish oil.

PMID- 19181366
TI  - Airborne particulate matter, platinum group elements and human health: a review
      of recent evidence.
AB  - Environmental concentrations of the platinum group elements (PGE) platinum (Pt),
      palladium (Pd) and rhodium (Rh) have been on the rise, due largely to the use of
      automobile catalytic converters which employ these metals as exhaust catalysts.
      It has generally been assumed that the health risks associated with environmental
      exposures to PGE are minimal. More recent studies on PGE toxicity, environmental
      bioavailability and concentrations in biologically relevant media indicate
      however that environmental exposures to these metals may indeed pose a health
      risk, especially at a chronic, subclinical level. The purpose of this paper is to
      review the most recent evidence and provide an up-to-date assessment of the risks
      related to environmental exposures of PGE, particularly in airborne particulate
      matter (PM). This review concludes that these metals may pose a greater health
      risk than once thought for several reasons. First, emitted PGE may be easily
      mobilised and solubilised by various compounds commonly present in the
      environment, thereby enhancing their bioavailability. Second, PGE may be
      transformed into more toxic species upon uptake by organisms. The presence of
      chloride in lung fluids, for instance, may lead to the formation of halogenated
      PGE complexes that have a greater potential to induce cellular damage. Third, a
      significant proportion of PGE found in airborne PM is present in the fine
      fraction that been found to be associated with increases in morbidity and
      mortality. PGE are also a concern to the extent that they contribute to the suite
      of metals found in fine PM suspected of eliciting a variety of health effects,
      especially in vulnerable populations. All these factors highlight the need to
      monitor environmental levels of PGE and continue research on their
      bioavailability, behaviour, speciation and associated toxicity to enable us to
      better assess their potential to elicit health effects in humans.

PMID- 19181368
TI  - Multiple human papillomavirus infection and high grade cervical intraepithelial
      neoplasia among women with cytological diagnosis of atypical squamous cells of
      undetermined significance or low grade squamous intraepithelial lesions.
AB  - OBJECTIVE: To evaluate the effect of multiple human papillomavirus (HPV)
      infection on the prevalence of cervical intraepithelial neoplasia (CIN) among
      women undergoing colposcopy following a cytological diagnosis of atypical
      squamous cells of undetermined significance (ASCUS) or low grade squamous
      intraepithelial lesions (LSIL). METHODS: HPV type-specific sequences of 15 high
      risk and 10 low risk types were detected by the line probe, INNO-LiPA HPV
      genotyping assay before colposcopic examination and targeted biopsies.
      Multinomial logistic regression was used to evaluate the effect of multiple
      infection on pathologic outcome adjusting for confounders. RESULTS: The
      prevalence of HPV infection in the 1218 women enrolled was 69.9% (851/1218). HPV
      16 (37.4%), 31 (26.1%), 51 (17.4%), 52 (15.7%) and 18 (14%) were the commonest
      viral types identified. Overall, the rates of multiple infection were 22.5%
      (153/680) among subjects with negative colposcopy/biopsy, 63.6% (218/343) and
      79.5% (155/195) among those with CIN 1 and CIN>or=2, respectively (p for trend
      <.001). The corresponding rates among subjects uninfected by HPV 16 or 18 were
      13.5% (77/572), 57.4% (112/195) and 62% (48/77), respectively (p for trend
      <.001). In multinomial logistic regression, the odds ratio of CIN>or=2 in
      multiple high risk as compared to single high risk HPV infection was 4.33 (95%
      confidence intervals=2.32-7.14) in the overall population and 2.76 (95%
      confidence intervals=1.36-5.59) among women uninfected by HPV 16 or 18.
      CONCLUSIONS: Multiple HPV infection is a significant risk factor for CIN>or=2
      among women undergoing colposcopy because of ASCUS/LSIL.

PMID- 19181367
TI  - Prolonged inhibition of protein kinase A results in metalloproteinase-dependent
      platelet GPIbalpha shedding.
AB  - INTRODUCTION: The interaction of platelet glycoprotein (GP) Ibalpha with von
      Willebrand factor (VWF) exposed at the injured vessel wall initiates platelet
      adhesion and thrombus formation. Thus GPIbalpha ectodomain shedding has important
      implications for thrombosis and hemostasis. A disintegrin and metalloproteinase
      17 (ADAM17) was identified recently to play an essential role in agonist induced
      GPIbalpha shedding. Here we show that prolonged inhibition of protein kinase A
      (PKA) results in metalloproteinase-dependent GPIbalpha shedding. METHODS AND
      RESULTS: GPIbalpha was shed from platelets prolongedly incubated with PKA
      inhibitors in a dose-dependent manner. In platelets treated with PKA inhibitor
      H89, the level of GPIbalpha shedding was significantly higher than that in
      calcium ionophore or alpha-thrombin treated platelets, however, P-selectin
      surface expression was significantly lower. PKA inhibition mediated GPIbalpha
      shedding was reversed by PKA activator forskolin and partially inhibited by
      membrane-permeable calpain inhibitors. Furthermore, the metalloproteinase
      inhibitor GM6001 or EDTA completely inhibited H89 induced GPIbalpha shedding,
      indicating that it was metalloproteinase-dependent. Time course experiments
      revealed that the maximum GPIbalpha shedding occurred at 30 minutes after
      treatment with PKA inhibitor. Platelets prolongedly treated with PKA inhibitor
      exhibited significant decrease in botrocetin-induced aggregation and shear
      induced adhesion on VWF. CONCLUSIONS: These data show that prolonged inhibition
      of PKA results in metalloproteinase-dependent platelet GPIbalpha ectodomain
      shedding. This finding has physiological implications for hemostasis and limiting
      thrombus infinite formation after platelet activation, and it also suggests a
      novel strategy to develop new drugs for thrombotic diseases.

PMID- 19181369
TI  - Feasibility study of neoadjuvant chemotherapy followed by interval debulking
      surgery for stage III/IV ovarian, tubal, and peritoneal cancers: Japan Clinical
      Oncology Group Study JCOG0206.
AB  - BACKGROUND: To assess the safety and efficacy of neoadjuvant chemotherapy (NAC)
      followed by interval debulking surgery (IDS) for mullerian carcinomas, such as
      ovarian, tubal, and peritoneal cancers, and to determine whether we can omit
      diagnostic laparoscopy before treatment initiation, a feasibility study was
      performed. METHODS: Eligible patients had presumed stage III/IV mullerian
      carcinomas clinically diagnosed by imaging studies, cytology, and tumor markers.
      All patients underwent diagnostic laparoscopy to confirm the clinical diagnosis.
      Four cycles of paclitaxel and carboplatin were administered as NAC, followed by
      interval debulking surgery and an additional 4 cycles of chemotherapy. The
      primary end point was the proportion of patients achieving clinical complete
      remission (cCR) among all stage III/IV mullerian carcinomas confirmed by
      diagnostic laparoscopy. The major secondary end point was the positive predictive
      value (PPV) of clinical diagnosis. RESULTS: Fifty-six patients were enrolled into
      the study. The PPV of overall clinical diagnosis for the tumor origin, histology,
      and stage was 95% (53/56). Fifty-three patients received the protocol treatment
      starting with NAC. IDS was performed in 89% (47/53) of patients. Complete
      resection without residual tumors was achieved in 55% (29/53) and residual tumors
      became <1 cm in 17% (9/53) of patients. Twenty-two patients (42%) achieved cCR
      after completion of the treatment. The median overall and progression-free
      survival was 45 and 14 months, respectively. CONCLUSION: NAC without diagnostic
      laparoscopy for advanced mullerian carcinomas holds sufficient promise to be
      compared with direct surgery in a phase III trial.

PMID- 19181370
TI  - The effect of sex on asthma control from the National Asthma Survey.
AB  - BACKGROUND: Previous studies have demonstrated conflicting results with regard to
      differences in asthma control between the sexes. OBJECTIVE: We sought to identify
      sex differences in short-term and long-term measures of asthma control in adults
      from the National Asthma Survey. METHODS: This study analyzed data from the
      National Asthma Survey (Four-State sample) sponsored by the National Center for
      Environmental Health, Centers for Disease Control and Prevention. Asthma control
      was compared between the sexes based on short-term (recent symptoms, asthma
      attacks, and albuterol use) and long-term (asthma attacks, work days lost, and
      urgent-care visits and hospitalizations in the prior year) measures. Composite
      scores for short-term and long-term control were calculated based on any single
      measure of poor asthma control and based on a sum of poor asthma control
      measures. RESULTS: Women were more likely to have poor short-term asthma control
      based on any measure (adjusted odds ratio [OR], 1.20; CI, 1.01-1.44) or sum of
      measures (adjusted OR, 1.24; CI, 1.08-1.53) compared with men. Women also
      demonstrated worse asthma control based on any uncontrolled long-term measure
      (adjusted OR, 1.52; CI, 1.29-1.79) or sum of measures (adjusted OR, 1.68; CI,
      1.45-1.93). These findings were present despite higher reported inhaled
      corticosteroid use and scheduled health care visits for asthma among women.
      CONCLUSIONS: Women demonstrated worse asthma control compared with men with
      regard to several short-term and long-term measures, despite reporting higher
      rates of inhaled corticosteroid use and routine asthma care visits. Further
      studies are needed to elucidate whether these findings are due to differences in
      health reporting or to pathophysiologic differences in asthma between the sexes.

PMID- 19181371
TI  - Pediatric Dyspnea Scale for use in hospitalized patients with asthma.
AB  - BACKGROUND: Asthma is a leading cause of pediatric hospitalizations across the
      country, yet no clinical instrument exists that incorporates the child's
      perception of dyspnea in determining discharge readiness. OBJECTIVE: We sought to
      develop the Pediatric Dyspnea Scale (PDS) to support discharge decision making in
      hospitalized asthmatic patients and to compare the performance of the PDS with
      traditional markers of asthma control in predicting outcomes after discharge.
      METHODS: Asthmatic children aged 6 to 18 years hospitalized for an exacerbation
      were included in the study. The PDS score, demographics, asthma severity,
      spirometric results, peak expiratory flow rate, and fraction of exhaled nitric
      oxide were assessed at the time of discharge. A telephone call 14 days after
      discharge determined relapse, activity limitation, asthma control, and asthma
      related quality-of-life outcomes. RESULTS: Eighty-nine patients were enrolled, of
      whom 70 completed the telephone follow-up. Eight patients had a relapse, and 29
      complained of limited activity. A PDS score of greater than 2 on the 7-point
      scale was a significant predictor of these poor outcomes, with each additional
      point of the PDS doubling the risk. A higher score on the PDS also correlated
      with worse asthma control and poor asthma-specific quality of life. The PDS
      performed better than FEV(1), peak expiratory flow rate, or fraction of exhaled
      nitric oxide in predicting the outcomes of interest. CONCLUSION: The PDS, which
      is easy to use in children as young as 6 years of age, might be able to predict
      adverse outcomes after hospitalization for an asthma exacerbation and should be
      used as a tool to help guide inpatient discharge decisions.

PMID- 19181372
TI  - Season of infant bronchiolitis and estimates of subsequent risk and burden of
      early childhood asthma.

PMID- 19181373
TI  - Parental support and cytokine activity in childhood asthma: the role of
      glucocorticoid sensitivity.
AB  - BACKGROUND: Stress is known to worsen the course of asthma, but the underlying
      mechanisms are poorly understood. This problem is especially difficult because
      stress elicits secretion of cortisol, a hormone that dampens airway inflammation
      and ameliorates asthma symptoms. OBJECTIVE: This article proposes that stress
      affects asthma by inducing resistance to the anti-inflammatory properties of
      glucocorticoids. To evaluate this hypothesis, we examine whether a particular
      kind of stress in children's lives, not feeling supported or understood by
      parents, is associated with in vitro measures of lymphocyte resistance to
      glucocorticoids and indices of eosinophil mobilization and activation. METHODS:
      Children with asthma (n = 67) and medically healthy children (n = 76) completed
      standardized questionnaires about support from their parents. PBMCs were
      collected and incubated with a mitogen cocktail in the presence of physiologic
      concentrations of hydrocortisone. Production of IL-5, IL-13, and IFN-gamma was
      measured by means of ELISA. Circulating eosinophils were enumerated with a
      hematology analyzer, and the extent of their activation was indexed by means of
      ELISA for eosinophil cationic protein. RESULTS: To the extent that children with
      asthma perceived low support from their parents, children were more resistant to
      hydrocortisone's anti-inflammatory effects on IL-5 and IFN-gamma production and
      had higher circulating levels of eosinophil cationic protein. These associations
      were independent of socioeconomic conditions, cigarette exposure, disease
      severity, and medication use. CONCLUSIONS: These patterns suggest the hypothesis
      that strained parent-child relations, and perhaps stress more generally, brings
      about adverse outcomes in asthma by diminishing cortisol's ability to regulate
      cytokine activity and subsequent airway inflammation.

PMID- 19181374
TI  - Effect of source of supplemental selenium on uterine health and embryo quality in
      high-producing dairy cows.
AB  - Lactating Holstein cows (n=135) were randomly assigned to one of the two sources
      of supplemental selenium (Se), sodium selenite (SS) or Se yeast (SY), fed at
      0.3mg/kg diet dry matter from 25 d before calving to 70 d in milk (DIM), in diets
      not suboptimal in basal Se concentrations. Cows were evaluated for health daily
      in the first 10 DIM, and uterine cytology of the previously gravid uterine horn
      was assessed at 30 DIM. The Ovsynch protocol was initiated at 42 DIM; ovarian
      responses to hormonal treatments were evaluated by ultrasonography. The uteri of
      cows were flushed 6d after timed AI for collection of embryos and oocytes. Plasma
      concentrations of Se and progesterone were measured throughout the postpartum
      period and during the reproductive protocol, respectively, and plasma glutathione
      peroxidase activity was determined 6d after AI. Concentrations of Se in pre- and
      postpartum diets ranged from 0.43 to 0.56 mg/kg of dry matter. Incidence of
      retained placenta, fever, ketosis, mastitis, acute puerperal metritis, clinical
      endometritis, and subclinical endometritis were not significantly different
      between treatments. There were no differences between groups in concentrations of
      Se and progesterone or glutathione peroxidase activity in plasma. Treatment did
      not influence ovarian responses to the synchronization protocol, fertilization
      rate, number of blastomeres and live blastomeres, or proportions of grades 1 and
      2, degenerated, and degenerated-unfertilized embryos/oocytes. Odds of subclinical
      endometritis on Day 30 postpartum more than doubled in cows with fever of unknown
      origin or acute puerperal metritis in the first 10 DIM. Fertilization rate tended
      to be reduced in cows with subclinical endometritis. In summary, replacing SS
      with an organic source of Se in diets not suboptimal in basal Se concentrations
      did not improve Se status, uterine health, fertilization, or embryo quality in
      early lactation dairy cows.

PMID- 19181375
TI  - Banking North American buffalo semen.
AB  - The purpose of this study was to develop a procedure to collect and preserve
      semen from wood bison (Bison bison athabascae) and plains bison (Bison bison
      bison). Semen samples from three wood and three plains bison bulls were collected
      by electroejaculation from June through October. In addition, sperm was collected
      from the cauda epididymis of seven plains bison. Semen was cryopreserved using
      two commercially available cryopreservation media, an egg yolk-based medium
      (Triladyl), and a medium free of products of animal origin (Andromed). Sperm
      morphology and motility were recorded on fresh and post-thawed semen samples.
      Total sperm motility was not different between plains and wood bison for the
      months of June (50%), July (69%) and October (54%). However, total sperm motility
      for wood bison was higher (P<0.05) than plains bison for the months of August and
      September (August: 80% vs 55%; September: 73% vs 40%). Plains and wood bison did
      not differ in mean total and mean progressive motility (35 and 15%, respectively)
      of frozen-thawed sperm samples. The post-thaw motility of Triladyl-treated sperm
      was higher (P<0.05) than Andromed-treated sperm (35% vs 13%, respectively).
      Interestingly, post-thawed epididymal spermatozoa had higher total motility
      (P<0.05) than post-thawed electroejaculated sperm when cryopreserved with a
      medium free of products of animal origin (Andromed; 35% vs 9%, respectively). In
      conclusion, we used electroejaculation to collect high quality bison semen, and
      cryopreserved it for future needs.

PMID- 19181376
TI  - The effect of addition of equine chorionic gonadotropin to a progesterone-based
      estrous synchronization protocol in buffaloes (Bubalus bubalis) under tropical
      conditions.
AB  - Poor estrus expression and anestrus decrease the reproductive efficiency of
      buffaloes. The objective of this study was to determine whether the addition of
      equine chorionic gonadotropin (eCG) to an estrous synchronization protocol and
      timed insemination could improve ovulation and pregnancy rates of anestrous
      buffalo cows under tropical conditions. The study population comprised 65
      lactating Murrah buffalo cows which were assigned to CIDR (n=33) or CIDR+eCG
      (n=32) treatment groups. Cows in the CIDR group were fitted for 8d with a
      controlled intravaginal drug release (CIDR) device containing 1.38 g
      progesterone, received GnRH (10 microg i.m.) on D 0, PGF(2alpha) (750 microg
      i.m.) on D 7, and GnRH (10 microg i.m.) on D 9; whereas cows in the CIDR+eCG
      group received the same treatment plus eCG (500 IU, i.m.) at the time of
      PGF(2alpha) treatment. All cows were inseminated 16-20 h after the second GnRH
      treatment. Blood samples were obtained 10d before the start of synchronization
      treatment (Day -10) and at the onset of treatment (Day 0). Cows with plasma
      progesterone concentrations <1 ng/mL recorded in both samples (Low-Low levels of
      P4) were classified as non-cyclic cows. Similarly, when either one or both of the
      sample pair contained concentrations of serum progesterone >/=1 ng/mL (High-High,
      Low-High, or High-Low levels of P4), the buffaloes were classified as cyclic
      cows. Ovulation rate, defined as the number of buffaloes with at least one corpus
      luteum 10 days after insemination, was significantly higher (P=0.018) in the
      CIDR+eCG (84.4%) cows than in the CIDR cows (57.6%). Pregnancy rate was
      numerically lower in CIDR (27.3%) than CIDR+eCG (40.6%) cows, though differences
      were not significant (P=0.25). Pregnancy rates for CIDR+eCG cows were similar to
      that of cows inseminated after natural estrus (40.9%; 29/71). In the non-cyclic
      animals, higher ovulation rates (P=0.026) were recorded for the CIDR+eCG (81%)
      than for the CIDR cows (47.4%). Our results indicate that the addition of eCG to
      a progesterone-based estrous synchronization regimen substantially improves the
      ovulation rate in non-cyclic buffaloes. When this treatment is followed by timed
      AI, pregnancy rates achieved in anestrous buffaloes, whether cyclic and non
      cyclic, may approach the rates observed in cows inseminated at natural estrus.

PMID- 19181377
TI  - All-trans-retinoic acid (ATRA)-grafted polymeric gene carriers for nuclear
      translocation and cell growth control.
AB  - Polyethyleneimine (PEI)-g-All-trans-retinoic acid (ATRA) (designated as PRA) was
      synthesized as a gene carrier. ATRA at its low concentration is known to be
      linked to nuclear translocation and cell cycle control (either proliferation or
      growth arrest) depending on its binding protein in cells. The cytotoxicity of PRA
      conjugates was lower than that of PEI and was gradually reduced as increasing
      ATRA graft ratios. The resulting nanosized and positively charged PRA/pDNA
      complexes showed lower transfection efficiency than the PEI/pDNA complexes
      (N/P=10) against NIH3T3 which is less sensitive to ATRA in cell growth and more
      sensitive HeLa cells. However, when a mixed gene complex of PEI and PRA was
      applied in an effort to reduce the ATRA contents, their NIH3T3 transfection
      evidenced effective nuclear translocation and induced 2- to 4-fold better
      transfection efficiency as compared with the PEI/pDNA complexes. When the
      PEI/pDNA complexes were utilized to transfect HeLa cells, free ATRA treatment
      reduced their cellular uptake and transfection efficiency. These findings show
      that the NIH3T3 cells against ATRA-mediated growth arrest would not damage the
      PRA-mediated transfection enhancement resulting from the facilitated nuclear
      translocation of polyplexes or pDNA. The more ATRA-sensitivity in growth arrest
      of HeLa cells would reduce the transfection efficiency of ATRA-incorporated
      polyplexes. The transfection capability of gene by newly synthesized PRA
      conjugates to cells is differentiated by their ATRA-sensitivity to nuclear
      translocation and cell growth control.

PMID- 19181379
TI  - Molecular variability of FLT3/ITD mutants and their impact on the differentiation
      program of 32D cells: implications for the biological properties of AML blasts.
AB  - FLT3 is the most frequently mutated gene in acute myeloid leukemia (AML), with
      internal tandem duplications (ITDs) accounting for up to 30% of its mutations. To
      analyze the impact of individual ITDs on the expression profile of immature
      myeloid cells, we have established 32D cell lines expressing nine different
      FLT3/ITDs isolated from AML patients and subjected them to whole genome
      expression profiling and 2DE/LC/MS proteomics. Our data indicate that in
      comparison to the controls, FLT3/ITD-positive 32D cells exhibit less mature
      expression profiles resembling early hematopoietic progenitors. Moreover, our
      results suggest that there exist biological differences among individual ITD
      variants.

PMID- 19181378
TI  - A small diameter, fibrous vascular conduit generated from a poly(ester
      urethane)urea and phospholipid polymer blend.
AB  - The thrombotic and hyperplastic limitations associated with synthetic small
      diameter vascular grafts have generated sustained interest in finding a tissue
      engineering solution for autologous vascular segment generation in situ. One
      approach is to place a biodegradable scaffold at the site that would provide
      acute mechanical support while vascular tissue develops. To generate a scaffold
      that possessed both non-thrombogenic character and mechanical properties
      appropriate for vascular tissue, a biodegradable poly(ester urethane)urea (PEUU)
      and non-thrombogenic bioinspired phospholipid polymer, poly(2
      methacryloyloxyethyl phosphorylcholine-co-methacryloyloxyethyl butylurethane)
      (PMBU) were blended at PMBU weight fractions of 0-15% and electrospun to create
      fibrous scaffolds. The composite scaffolds were flexible with breaking strains
      exceeding 300%, tensile strengths of 7-10MPa and compliances of 2.9-4.4 x 10(-4)
      mmHg(-1). In vitro platelet deposition on the scaffold surfaces significantly
      decreased with increasing PMBU content. Rat smooth muscle cell proliferation was
      also inhibited on PEUU/PMBU blended scaffolds with greater inhibition at higher
      PMBU content. Fibrous vascular conduits (1.3mm inner diameter) implanted in the
      rat abdominal aorta for 8 weeks showed greater patency for grafts with 15% PMBU
      blending versus PEUU without PMBU (67% versus 40%). A thin neo-intimal layer with
      endothelial coverage and good anastomotic tissue integration was seen for the
      PEUU/PMBU vascular grafts. These results are encouraging for further evaluation
      of this technique in larger diameter applications for longer implant periods.

PMID- 19181380
TI  - Metachronous and synchronous presentation of acute myeloid leukemia and lung
      cancer.
AB  - Smoking is associated with both acute myeloid leukemia (AML) and lung cancer. We
      therefore searched our database for concomitant presentation of AML and lung
      cancer. Among 775 AML cases and 5225 lung cancer cases presenting to Roswell Park
      Cancer Institute between the years January 1992 and May 2008 we found 12 (1.5% of
      AML cases; 0.23% of lung cancer cases) cases (seven metachronous and five
      synchronous) with AML and lung cancer. All but one patient were smokers. There
      were no unique characteristic of either AML or lung cancer in these patients.
      Nine patients succumbed to AML, one died from an unrelated cause while undergoing
      treatment for AML, one died of lung cancer and one patient is alive after
      allogeneic transplantation for AML. In summary, this study supports the need for
      effective smoking cessation programs.

PMID- 19181381
TI  - Intersex in Littorina littorea and DNA damage in Mytilus edulis as indicators of
      harbour pollution.
AB  - Intersex in snails (Littorina littorea) and DNA damage in blue mussels (Mytilus
      edulis) were analysed to assess how these bio-indicators reflected the level of
      chemical contamination at two sites in a highly contaminated harbour in Denmark.
      The comet assay using mussel gill cells was an indicator of exposure to genotoxic
      chemicals, and the intersex index (ISI) observed in snails was an indicator of
      exposure to butyltin (BT) compounds. Biota and sediments were analysed for heavy
      metals (Cd, Cu, Pb and Zn), butyltin compounds (TBT, DBT and MBT), nine PCB
      congeners and 19 PAH compounds. The biological effects were found to reflect the
      levels of the chemicals, and it was concluded that intersex in L. littorea and
      DNA damage in M. edulis can be used as bio-indicators of harbour pollution.

PMID- 19181382
TI  - Feeding the masses: H.J. Heinz and the creation of industrial food.
AB  - The H.J. Heinz Company's commitment to the purity and quality of its products in
      the late nineteenth and early twentieth century helped usher in an era of
      industrial food. While canning had been around for decades, it was not until both
      scientist and technologists innovations solved problems like bacterial
      contamination and mass-produced cans that Americans began to eat canned food on a
      regular basis. In addition to money-back guarantees, Heinz pioneered product
      tastings as a marketing tool in an attempt to convince skeptical housewives that
      his products were not only delicious, but were also safe to eat.

PMID- 19181383
TI  - The kinase activities of interleukin-1 receptor associated kinase (IRAK)-1 and 4
      are redundant in the control of inflammatory cytokine expression in human cells.
AB  - IRAK-1 and IRAK-4 are protein kinases that mediate signaling by Toll/IL1/Plant R
      (TIR) domain-containing receptors including the IL-1, IL-18, and Toll-like
      receptors (TLRs). Although well studied in mouse systems, the mechanism by which
      they function in human systems is less clear. To extend our knowledge of how
      these proteins regulate inflammatory signaling in human cells, we genetically and
      pharmacologically manipulated IRAK-1 and IRAK-4 kinase activities in vitro.
      Ablation of IRAK-4 expression in human umbilical vein endothelial cells (HUVEC)
      with siRNA suppressed IL-1beta induced IL-6 and IL-8 production whereas IRAK-1
      siRNA suppressed TNFalpha induced but not IL-1beta induced cytokine production.
      Complementation of IRAK-4-depleted cells with a kinase-inactive allele restored
      IL-1beta induced cytokine gene expression suggesting that the IRAK-4 kinase
      activity is dispensable relative to its scaffolding function. Consistent with
      this finding, an IRAK-4 selective kinase inhibitor (RO6245) that inhibited IRAK-1
      degradation failed to block IL-1beta induced cytokine production. In contrast, an
      inhibitor of both IRAK-1 and IRAK-4 (RO0884) reduced IL-1beta induced p38 MAP
      kinase, c-Jun N-terminal kinase activation, and IL-6 production in HUVEC. RO0884
      also antagonized IL-1beta, TNFalpha, and TLR-mediated cytokine production in
      human fibroblast-like synoviocytes and peripheral blood mononuclear cells.
      Therefore in human cells the non-kinase functions of IRAK-4 are essential,
      whereas the kinase activity of IRAK-4 appears redundant with that of IRAK-1.
      Pharmacologic inhibition of both kinases appears necessary to block pro
      inflammatory cytokine production.

PMID- 19181385
TI  - GANP suppresses the arginine methyltransferase PRMT5 regulating IL-4-mediated
      STAT6-signaling to IgE production in B cells.
AB  - Antigen (Ag)-driven B cells undergo antibody (Ab) affinity maturation and class
      switching in germinal center (GC) B cells. GANP is one of the molecules required
      for Ab affinity maturation. We herein found an increase of IgE in B cell ganp
      deficient mice and studied the signal transduction pathway regulated by GANP.
      GANP suppresses the STAT-mediated transcription activity in GC B cells with the
      regulation of arginine methyltransferase activity by the interaction with JAK
      binding protein arginine methyltransferase (PRMT) 5 and JAK1/JAK3 that are
      responsible for STAT6 activation. The prmt5 mRNA was up-regulated in B cells
      after stimulation in vitro and in vivo in GC B cells. The loss of GANP caused up
      regulation of phosphorylation and arginine dimethylation of STAT6 in B cells
      after stimulation with LPS and IL-4 in vitro. On the contrary, GANP over
      expressed B cells in ganp gene-transgenic mice showed a low STAT6 phosphorylation
      after stimulation. The over-expression of PRMT5 caused the up-regulation of STAT6
      mediated gene transcription, which was also suppressed by the co-transfection of
      GANP, in luciferase reporter assay. GANP down-regulates JAK1/JAK3 to STAT6
      signaling with regulation of arginine methylation activity, which might be
      responsible for the B cell endogenous suppressive mechanism of hyper-IgE.

PMID- 19181384
TI  - Enforced covalent trimerisation of soluble feline CD134 (OX40)-ligand generates a
      functional antagonist of feline immunodeficiency virus.
AB  - The feline immunodeficiency virus (FIV) targets activated CD4-positive helper T
      cells preferentially, inducing an AIDS-like immunodeficiency in its natural host
      species, the domestic cat. The primary receptor for FIV is CD134, a member of the
      tumour necrosis factor receptor superfamily (TNFRSF) and all primary viral
      strains tested to date use CD134 for infection. To investigate the effect of the
      natural ligand for CD134 on FIV infection, feline CD134L was cloned and expressed
      in soluble forms. However, in contrast to murine or human CD134L, soluble feline
      CD134L (sCD134L) did not bind to CD134. Receptor-binding activity was restored by
      enforced covalent trimerisation following the introduction of a synthetic
      trimerisation domain from tenascin (TNC). Feline and human TNC-CD134Ls retained
      the species-specificity of the membrane-bound forms of the ligand while murine
      TNC-CD134L displayed promiscuous binding to feline, human or murine CD134. Feline
      and murine TNC-CD134Ls were antagonists of FIV infection; however, potency was
      both strain-specific and substrate-dependent, indicating that the modulatory
      effects of endogenous sCD134L, or exogenous CD134Lbased therapeutics, may vary
      depending on the viral strain.

PMID- 19181386
TI  - Autoimmunogenicity of the helix-loop-helix DNA-binding domain.
AB  - Nonimmunogenic character of native DNA, and its high immunogenicity when
      presented in complex with the DNA-binding proteins indicate that the latter might
      contain molecular triggers of anti-DNA response. To find if this is the case, we
      have evaluated the autoimmunogenic potential of the main DNA-binding domain of
      HIV-1 reverse transcriptase that belongs to the canonical helix-loop-helix type.
      BALB/c mice were immunized with a peptide representing the domain, alone or in
      complex with the fragmented human DNA in the presence of an adjuvant. Mice were
      assessed for specific antibodies, autoantibodies against a panel of self
      antigens; glomerular immunoglobulin deposition; and for the signs of autoimmune
      disease, such as proteinuria, and changes in the blood components. Immunization
      with the adjuvanted peptide-DNA complex induced autoantibodies against double
      stranded DNA, histones, heterochromatin, and kidney proteins; glomerular IgG and
      IgA deposition; proteinuria; thrombocytopenia, and anemia. Altogether, this
      identifies the helix-loop-helix DNA-binding domain as one of the molecular
      triggers of autoimmunity to DNA and DNA-associated proteins. The experiments cast
      new light on the role of the DNA-binding retroviral proteins in the induction of
      autoimmunity, and on the origins of autoimmune complications in the microbial
      infections in general. It also implies that choosing the DNA-binding proteins as
      vaccine candidates should be done with precaution.

PMID- 19181387
TI  - Elevated IL-6 expression in CD4 T cells via PKCtheta and NF-kappaB induces Th2
      cytokine production.
AB  - T helper (Th) cell differentiation is a key event to mount an appropriate immune
      response. Th1 and Th2 cells produce their signature cytokines IFN-gamma and IL-4,
      respectively. However, as we have reported, CD4 T cells selected by MHC class II
      expressing thymocytes (T-CD4) produce both Th1 and Th2 type cytokines under Th1
      differentiation conditions. Furthermore, the expression of Th2 cytokines in these
      cells is Stat6 independent. In the current study, we investigated the molecular
      mechanisms by which CD4 T cells produce Th2 cytokines under the Th1
      differentiation condition. We observed that IL-6 is highly expressed in T-CD4 T
      cells, which is at least partly responsible for Th2 cytokine production by Th1
      differentiated cells. The enhanced expression of IL-6 is downstream of
      constitutive phosphorylation of PKCtheta and high NF-kappaB activity.
      Neutralizing IL-6, blocking PKCtheta phosphorylation, or inhibiting NF-kappaB
      translocation diminished Th2 cytokine expression in Th1 cultures. Therefore, our
      study revealed that autocrine IL-6 production can induce Th2 cytokine production,
      and that PKCtheta and NF-kappaB are essential components in the induction of IL-6
      mediated Th2 development.

PMID- 19181388
TI  - Toxicological effects of inorganic nanoparticles on human lung cancer A549 cells.
AB  - Many researches have shown that anionic clays can be used as delivery carriers
      for drug or gene molecules due to their efficient cellular uptake in vitro, and
      enhanced permeability and retention effect in vivo. It is, therefore, highly
      required to establish a guideline on their potential toxicity for practical
      applications. The toxicity of anionic clay, layered metal hydroxide nanoparticle,
      was evaluated in two human lung epithelial cells, carcinoma A549 cells and normal
      L-132 cells, and compared with that in other human cancer cell lines such as
      cervical adenocarcinoma cells (HeLa) and osteosarcoma cells (HOS). The present
      nanoparticles showed little cytotoxic effects on the proliferation and viability
      of four cell lines tested at the concentrations used (<250 microg/ml) within 48
      h. However, exposing cancer cells to high concentrations (250-500 microg/ml) for
      72 h resulted in an inflammatory response with oxidative stress and membrane
      damage, which varied with the cell type (A549>HOS>HeLa). On the other hand, the
      toxicity mechanism seems to be different from that of other inorganic
      nanoparticles frequently studied for biological and medicinal applications such
      as iron oxide, silica, and single walled carbon nanotubes. Iron oxide caused cell
      death associated with membrane damage, while single walled carbon nanotube
      induced oxidative stress followed by apoptosis. Silica triggered an inflammation
      response without causing considerable cell death for both cancer cells and normal
      cells, whereas layered metal hydroxide nanoparticle did not show any cytotoxic
      effects on normal L-132 cells in terms of inflammation response, oxidative
      stress, and membrane damage at the concentration of less than 250 microg/ml. It
      is , therefore, highly expected that the present nanoparticle can be used as a
      efficient vehicle for drug delivery and cancer cell targeting as well.

PMID- 19181389
TI  - Pathophysiology of depression: role of sleep and the melatonergic system.
AB  - Profound disturbances in sleep architecture occur in major depressive disorders
      (MDD) and in bipolar affective disorders. Reduction in slow wave sleep, decreased
      latency of rapid eye movement (REM) sleep and abnormalities in the timing of
      REM/non-REM sleep cycles have all been documented in patients with MDD. It is
      thus evident that an understanding of the basic mechanisms of sleep regulation is
      essential for an analysis of the pathophysiology of depressive disorders. The
      suprachiasmatic nucleus (SCN), which functions as the body's master circadian
      clock, plays a major role in the regulation of the sleep/wakefulness rhythm and
      interacts actively with the homeostatic processes that regulate sleep. The
      control of melatonin secretion by the SCN, the occurrence of high concentrations
      of melatonin receptors in the SCN, and the suppression of electrical activity in
      the SCN by melatonin all underscore the major influence which this neurohormone
      has in regulating the sleep/wake cycle. The transition from wakefulness to high
      sleep propensity is associated with the nocturnal rise of endogenous melatonin
      secretion. Various lines of evidence show that depressed patients exhibit
      disturbances in both the amplitude and shape of the melatonin secretion rhythm
      and that melatonin can improve the quality of sleep in these patients. The choice
      of a suitable antidepressant that improves sleep quality is thus important while
      treating a depressive disorder. The novel antidepressant agomelatine, which
      combines the properties of a 5-HT(2C) antagonist and a melatonergic MT(1)/MT(2)
      receptor agonist, has been found very effective for resetting the disturbed
      sleep/wake cycle and in improving the clinical status of MDD. Agomelatine has
      also been found useful in treating sleep problems and improving the clinical
      status of patients suffering from seasonal affective disorder.

PMID- 19181391
TI  - The most cited and requested articles published in the International Journal of
      Pediatric Otorhinolaryngology.

PMID- 19181390
TI  - Selective uptake of multi-walled carbon nanotubes by tumor macrophages in a
      murine glioma model.
AB  - Carbon nantotubes (CNTs) are emerging as a new family of nanovectors for drug and
      gene delivery into biological systems. To evaluate potential application of this
      technology for brain tumor therapy, we studied uptake and toxicity of multi
      walled CNTs (MWCNTs) in the GL261 murine intracranial glioma model. Within 24 h
      of a single intratumoral injection of labeled MWCNTs (5 microg), nearly 10-20% of
      total cells demonstrated CNT internalization. Most CNT uptake, however, occurred
      by tumor-associated macrophages (MP), which accounted for most (75%) MWCNT
      positive cells. Within 24 h of injection, nearly 30% of tumor MP became MWCNT
      positive. Despite a transient increase in inflammatory cell infiltration into
      both normal and tumor-bearing brains following MWCNT injection, no significant
      toxicity was noted in mice, and minor changes in tumor cytokine expression were
      observed. This study suggests that MWCNTs could potentially be used as a novel
      and non-toxic vehicle for targeting MP in brain tumors.

PMID- 19181392
TI  - Speech assessment in cleft palate patients: a descriptive study.
AB  - OBJECTIVE: Speech disorders could affect the intelligibility, but also social
      competence and emotional development of a cleft-palate child. In this study, we
      proposed to examine the phono-articulatory defects of a group of surgically
      treated cleft palate patients, relatively to the familial social background, and
      children ability of self-controlling during spontaneous language. METHODS: Sixty
      eight children (22 males and 46 females) mean age 6.87 years, affected by a non
      syndromic isolated cleft of the palate underwent to the same surgical protocol.
      Linguistic level was evaluated using the speech assessment protocol of Accordi
      and colleagues that focuses on intelligibility, nasality, nasal air escape,
      pharyngeal friction, and glottal stop. Each of these parameters is evaluated on a
      four-point scale, ranging from 0 to 3. Spearman rank order correlation was used
      to detect significant association between analyzed parameters; also the patient
      social background was considered for statistical analysis. RESULTS: The 5.88% of
      the sample had a negative result, with a severe to moderate degree of nasality
      and nasal air escape, presence of pharyngeal friction and glottal stop and,
      obviously a systematic compromising of the intelligibility. Also grimace was
      evident. The 38.23% of the sample showed an acceptable phonological outline;
      nasality and nasal air escape were mild, and the intelligibility resulted normal.
      Thirty-eight children (55.88%) showed a perfectly normal speech. Statistical
      analysis (Spearman rank order correlation) revealed a positive correlation
      between the severity of nasality and nasal air escape and the patient social
      contest of life (p</=0.05); moreover, there was a positive correlation between
      nasality and nasal air escape with the final intelligibility (p<or=0.05), and
      between the intelligibility and the patient social contest of life. CONCLUSION:
      Phonetic and phonological development in cleft child are not only due to the
      surgical strategies and the surgeon experience, but also influenced by the
      willingness to collaborate of the patient and especially of the parents, the
      timeliness of the logopaedic intervention, and by inborn capabilities of the
      child to control the emission of the air from nasal and oral cavities.

PMID- 19181393
TI  - Activities of 30 years of Japan Society for Pediatric Otorhinolaryngology.

PMID- 19181394
TI  - History and evolution of pediatric otolaryngology (PED ENT) in Latin America.
AB  - This paper will provide a description of pediatric otolaryngology and its history
      and evolution in Latin America.

PMID- 19181395
TI  - Foreign body aspiration in children: a nationwide survey in Japan.
AB  - BACKGROUND: Foreign body aspiration (FBA) is a common cause for a respiratory
      emergency in young children and can be a life-threatening event. We, therefore,
      conducted the first nationwide survey in Japan. METHODS: We asked doctors of 261
      tertiary hospitals across the nation to fill out a case card of FBA-diagnosed
      cases they had experienced for the past 2 years. In the case card, age and gender
      of the patients, elapsed time until being referred to the hospital, presenting
      symptoms, previous diagnosis, suspected aspiration episode, type and location of
      aspirated foreign body, and consequences were inquired. This retrospective survey
      was carried out during 21 months, since January 2005 through September 2006.
      RESULTS: Replies from 169 hospitals (64.8%) revealed that 163 cases of FBA had
      been treated in 114 hospitals during the past 2 years. Median age of cases was 1
      year (2 months to 15 years), and 66.5% were male. Only 50.9% of the cases were
      referred to hospitals within 24h. Comparing these early-diagnosed cases, children
      with delayed diagnosis had similar age and sex distribution. In respect of
      presenting symptoms, characteristic ones such as choking or dyspnea were observed
      significantly more often in the early-diagnosed cases, whereas significantly
      predominant symptoms in children with delayed diagnosis were non-specific ones
      like coughing and wheezing (both, p<0.05). Although significantly more cases with
      early diagnosis reported suspected aspiration episodes (p<0.05), even in the
      delayed diagnosis group more than half cases (65%) had suspected episodes as
      well. Severe consequences occurred in seven cases (4.3%): four cases of
      irreversible hypoxic brain damage and one death due to multiorgan failure in the
      early diagnosis group; one bronchiectasis and one recurrent pneumonia in the
      delayed diagnosis group. CONCLUSIONS: Characteristics of FBA among children in
      Japan were not substantially different from the reports from other countries.
      Suspected episodes were important, and there were some differences in presenting
      symptoms between early and delayed diagnosis cases. However, there are still no
      key sings to make a prompt diagnosis. In order to prevent FBA and make a timely
      diagnosis, continuous and extensive educational programs should be provided.

PMID- 19181397
TI  - Post-operative bleeding is less after partial intracapsular tonsillectomy than
      bipolar total procedure.
AB  - OBJECTIVE: To compare bleeding after partial intracapsular tonsillectomy (PIT)
      and bipolar diathermy tonsillectomy (BDT). DESIGN: Retrospective chart review.
      SETTING: Stollery Children's Hospital, tertiary pediatric referral centre.
      PATIENTS: All children (<or=17 years of age) who had tonsillectomy. Patients who
      had incomplete information or less than 2-weeks follow-up were excluded. MAIN
      OUTCOME MEASURE: (1) Post-tonsillectomy bleeding, (2) other data collected
      included demographics, length of follow-up, indication(s) for surgery, other
      procedures performed, and co-morbidities. RESULTS: Over a 4.5-year period 677
      patients (333 BDT, 344 PIT) were identified in our search, and 77 (38 BDT, 39
      PIT) were excluded. The mean age was 7.7+/-3.8 years in the BDT group and 6.5+/
      3.2 years in the PIT group. Sex distribution was similar in the 2 groups (chi
      square p=0.61). Twenty (6.8%) BDT patients experienced post-tonsillectomy
      bleeding, compared to three (0.98%) of PIT patients (p=0.0001, 95% CI 1.52-2.18,
      OR=7.32). Over 3 times as many PIT patients (153) had co-morbid conditions than
      BDT patients (44); this was statistically significant (chi square p<0.00001, 95%
      CI 1.78-2.38). CONCLUSION: PIT results in significantly less post-tonsillectomy
      bleeding than BDT. These findings favor partial over total techniques with
      respect to reducing this important complication.

PMID- 19181398
TI  - Pathways of trace metal uptake in the lugworm Arenicola marina.
AB  - Radiotracer techniques were used to determine the rates of trace metal (Ag, Cd
      and Zn) uptake and elimination (33 psu, 10 degrees C) from water and sediment by
      the deposit-feeding polychaete Arenicola marina, proposed as a test species for
      estuarine-marine sediments in whole-sediment toxicity tests. Metal uptake rates
      from solution increase with increasing dissolved metal concentrations, with
      uptake rate constants (+/-SE) (lg(-1) d(-1)) of 1.21+/-0.11 (Ag), 0.026+/-0.002
      (Zn) and 0.012+/-0.001 (Cd). Assimilation efficiencies from ingested sediments
      were measured using a pulse-chase radiotracer feeding technique in two different
      lugworm populations, one from a commercial supplier (Blyth, Northumberland, UK)
      and the other a field-collected population from the outer Thames estuary (UK).
      Assimilation efficiencies ranged from 2 to 20% for Zn, 1 to 6% for Cd and 1 to 9%
      for Ag for the Northumberland worms, and from 3 to 22% for Zn, 6 to 70% for Cd
      and 2 to 15% for Ag in the case of the Thames population. Elimination of
      accumulated metals followed a two-compartment model, with similar efflux rate
      constants for Zn and Ag and lower rates of elimination of Cd from the slow pool.
      Efflux rate constants (+/-SE) of Zn and Ag accumulated from the dissolved phase
      were 0.037+/-0.002 and 0.033+/-0.006 d(-1) whereas Cd was eliminated with an
      efflux rate constant one order of magnitude lower (0.003+/-0.002 d(-1)). When
      metals were accumulated from ingested sediments, the efflux rate constants for
      the slow-exchanging compartment were of the same order of magnitude for the three
      metals, and of the same order of magnitude as those derived after the dissolved
      exposure for Zn and Ag (0.042+/-0.004 and 0.056+/-0.012 d(-1) for Zn and 0.044+/
      0.012 and 0.069+/-0.016 d(-1) for Ag for the Northumberland and Thames
      populations, respectively). Cd accumulated from ingested sediments was eliminated
      with a rate constant not different from the fast-exchanging compartment after the
      water-only exposure (0.025+/-0.012 and 0.020+/-0.004 d(-1) for the Northumberland
      and Thames populations, respectively). A biodynamic model was used to estimate
      the relative importance of the dissolved phase versus ingested sediment as source
      of metal for the worms, showing that more than 90% of the Zn and Cd and more than
      70% of Ag in lugworms is accumulated from sediment ingestion at realistic
      environmental concentrations. The model also shows that metal accumulation is
      highly dependent on the ingestion rate and assimilation efficiency.

PMID- 19181399
TI  - Self-rated health in patients with mild Alzheimer's disease: baseline data from
      the Danish Alzheimer Intervention Study.
AB  - In both epidemiological studies and in clinical trials the patients' own health
      perception, self-rated health (SRH), measured by a single question, is frequently
      used as an overall health assessment. Researchers have been encouraged to examine
      ways of assessing SRH in cognitively impaired persons, but the validity and the
      influence on other factors on SRH among cognitively impaired persons remain
      unknown. This study reports how patients with mild Alzheimer's disease (AD)
      report SRH and which factors influence SRH. The study was based on baseline data
      from 321 home living patients with mild AD who participated in the Danish
      Alzheimer Intervention Study (DAISY). Analysis using the generalized estimating
      equation (GEE) models revealed that good/excellent SRH among patients with mild
      AD were associated with longer education, lack of other chronic conditions,
      higher scores of quality of life (QOL), lower scores of mini mental state
      examination (MMSE), and loss of insight in own cognitive deficits. The present
      results indicate that SRH reported by patients with mild AD may differ from SRH
      among cognitively intact persons. Further research is needed in order to
      establish the validity and implication of SRH in this group of patients.

PMID- 19181400
TI  - Monitoring of heart rate variability in heart failure patients with cardiac
      resynchronisation therapy: interest of continuous and didactic algorithm.

PMID- 19181402
TI  - Coronary embolism.

PMID- 19181401
TI  - Autologous transplantation of EPCs encoding FGF1 gene promotes neovascularization
      in a porcine model of chronic myocardial ischemia.
AB  - OBJECTIVES: The functional impairment of endothelial progenitor cells (EPCs)
      constitutes an important barrier for therapeutic angiogenesis. Here, we tested
      the hypotheses that a secreted version of acidic fibroblast growth factor (sp
      FGF1) gene transfer may achieve functional improvement of EPCs and that
      autologous transplantation of sp-FGF1-modified EPCs can facilitate
      neovascularization in a porcine model of chronic myocardial ischemia. METHODS AND
      RESULTS: EPCs were cultured from porcine peripheral blood and transduced with a
      recombinant adeno-associated virus encoding the sp-FGF1 gene (Td/FGF1-EPC). EPC
      function was evaluated 3 days after the gene transfer. In vitro, the sp-FGF1
      modified EPCs displayed enhanced migration, tube formation and survival. Chronic
      myocardial ischemia was induced by the placement of an ameroid constrictor around
      the left circumflex coronary artery (LCx). Four weeks after ameroid placement,
      coronary angiography was performed and the cells were administered through the
      stenotic LCx. Myocardial perfusion defects were significantly reduced in animals
      transplanted with Td/FGF1-EPC compared to animals that received non-transduced
      EPCs or PBS (P<0.05) as assessed by SPECT 4 weeks after cell transplantation.
      Furthermore, the vascular density of ischemic myocardium was significantly
      increased in Td/FGF1-EPC transplanted animals (P<0.05). In addition, FGF1 protein
      expression was only detected in Td/FGF1-EPC transplanted animals. CONCLUSIONS:
      The functional activities of EPCs were enhanced by sp-FGF1 gene transfer.
      Transplantation of this gene modified EPCs promoted neovascularization in a
      porcine model of chronic myocardial ischemia, indicating the therapeutic
      potential of this cell-based gene therapy strategy for the treatment of ischemic
      diseases.

PMID- 19181403
TI  - Revelation of an obstructive hypertrophic cardiomyopathy in an elderly patient.
AB  - Hypertrophic cardiomyopathy (HCM) is classified as a primary cardiomyopathy. HCM
      is a clinically heterogeneous but relatively common autosomal dominant genetic
      heart disease that probably is the most frequently occurring cardiomyopathy. HCM
      is characterized morphologically and defined by a hypertrophied, nondilated left
      ventriculum (LV) in the absence of another systemic or cardiac disease that is
      capable of producing the magnitude of wall thickening evident (e.g., systemic
      hypertension, aortic valve stenosis). Most HCM patients have the propensity to
      develop dynamic obstruction to LV outflow under resting or physiologically
      provocable conditions, produced by systolic anterior motion of the mitral valve
      with ventricular septal contact. The phenotypic features of HCM may develop at
      any age from infancy to adulthood, and are characterized by a great heterogeneity
      in the extent, magnitude, and distribution of left ventricular hypertrophy.
      Hypertrophic obstructive cardiomyopathy (HOCM) often leads to heart failure,
      severe ischemia, severe symptoms and death. Determination of the exact site of
      the hypertrophy and of the obstruction of the left ventricular outflow tract, in
      asymmetric septal hypertrophy, establishes which is the best treatment strategy.
      In the treatment of HOCM, drug therapy with negatively inotropic drugs,
      percutaneous transluminal septal myocardial ablation by alcohol-induced septal
      branch occlusion, surgical myectomy and DDD pacemaker therapy are considered the
      therapeutical options. We present a case of an obstructive hypertrophic
      cardiomyopathy in an 84-year-old Italian woman with a left ventricular outflow
      tract (LVOT) peak gradient with the Valsalva maneuver of 188 mm Hg and with a
      history of first episode of syncope.

PMID- 19181404
TI  - Isolated left ventricular non-compaction: a larger part of submerged iceberg with
      criteria for diagnosis to the limits of standard.

PMID- 19181405
TI  - Treatment failure of low molecular weight heparin in a patient with an aortic
      mechanical prosthesis.
AB  - After mechanical heart valve replacement use of unfractionated heparin is
      sometimes required because vitamin K antagonists are temporarily contraindicated
      or to prevent valve-associated thromboembolism until oral vitamin K antagonists
      take effect. Bridging therapy with a standardized low molecular weight heparin
      based regimen has been reported effective and relatively safe in a large cohort
      of patients with mechanical heart valves. Many cases with mitral mechanical valve
      prostheses and treatment failure of low molecular weight heparin have also been
      reported as well as prosthetic valve thrombosis has been reported with adequate
      anticoagulation. A case has also been reported of well functioning Starr-Edwards
      aortic prosthesis without anticoagulation. We present a case of cardioembolic
      stroke in a patient with an aortic mechanical prosthesis in bridging therapy with
      a standardized low molecular weight heparin-based regimen. This case is
      illustrative of treatment failure of low molecular weight heparin in a patient
      with an aortic mechanical prosthesis.

PMID- 19181406
TI  - Pacemaker activity of the human sinoatrial node: role of the hyperpolarization
      activated current, I(f).
AB  - The mechanism of primary, spontaneous cardiac pacemaker activity of the
      sinoatrial node (SAN) has extensively been studied in several animal species, but
      is virtually unexplored in man. Understanding the mechanisms of human SAN
      pacemaker activity is important for developing new therapeutic approaches for
      controlling the heart rate in the sick sinus syndrome and in diseased myocardium.
      Here we review the functional role of the hyperpolarization-activated 'funny'
      current, I(f), in human SAN pacemaker activity. Despite the many animal studies
      performed over the years, the contribution of I(f) to pacemaker activity is still
      controversial and not fully established. However, recent clinical data on
      mutations in the I(f) encoding HCN4 gene, which is thought to be the most
      abundant isoform of the HCN gene family in SAN, suggest a functional role of I(f)
      in human pacemaker activity. These clinical findings are supported by recent
      experimental data from single isolated human SAN cells that provide direct
      evidence that I(f) contributes to human SAN pacemaker activity. Therefore,
      controlling heart rate in clinical practice via I(f) blockers offers a valuable
      approach to lowering heart rate and provides an attractive alternative to
      conventional treatment for a wide range of patients with confirmed stable angina,
      while upregulation or artificial expression of I(f) may relieve disease-causing
      bradycardias.

PMID- 19181407
TI  - Association of angiographic morphology with high-sensitivity C-reactive protein
      levels in patients with coronary spastic angina.
AB  - Relationship between angiographic morphology and high-sensitivity C-reactive
      protein (hs-CRP) levels is not fully understood. The serum levels of hs-CRP
      levels were higher in focal than in diffuse vasospasm in patients with coronary
      spastic angina. Intravascular ultrasound showed greater plaque volume at the site
      of vasospasm in the focal vasospasm, in the absence of significant angiographic
      stenosis, whereas diffuse intimal thickening throughout the coronary arteries was
      observed in the diffuse vasospasm. The distinct differences in the hs-CRP levels
      may be closely associated with coronary plaque appearances.

PMID- 19181408
TI  - Plasma homocysteine and cardiovascular risk in heart failure with and without
      cardiorenal syndrome.
AB  - INTRODUCTION: Plasma homocysteine (Hcy) has been associated with an increased
      cardiovascular (CV) risk in patients with chronic heart failure (CHF). Thus, we
      investigated whether Hcy has a prognostic impact on CV events in CHF-patients
      with and without cardiorenal syndrome (CRS). METHODS: 161 patients with CHF were
      included in the present analysis. 94 patients had systolic (SD) (EF <40%) and 67
      diastolic (DD) dysfunction (EF>or=40%). 60 had cardiorenal syndrome (CRS+
      creatinine clearance<60 ml/min). Mean ejection fraction was 38+/-16% (n=153) and
      mean VO2 max 19+/-7 ml/min (n=87). RESULTS: Homocysteine is significantly
      increased in patients with CHF (20+/-7 micromol/l). The increase correlates not
      only with the severity of the disease (NYHA, EF, VO2max), but also with various
      metabolic (BNP, uric acid) and nephrologic parameters (creatinine, creatinine
      clearance). During follow-up (23+/-37 months), patients with the highest
      homocysteine (>or=20 micromol/l) passed away more often (p<0.035) or
      decompensated more frequently (p<0.004) than those with a low Hcy. In patients
      with CRS the rate of decompensation was significantly higher than in those
      without CRS (p<0.0007). CONCLUSIONS: Homocysteine is an important marker for an
      increased CV risk in patients with CHF. A homocysteine of >/=20 micromol/l is
      associated with a high risk to decompensate or to die (odds ratio 2.57). The
      presence of CRS is also associated with an increased CV risk (odds ratio 3.7) and
      predicts an adverse clinical outcome.

PMID- 19181409
TI  - Volumetric-modulated arc radiotherapy for carcinomas of the anal canal: A
      treatment planning comparison with fixed field IMRT.
AB  - PURPOSE: A treatment planning study was performed to compare volumetric-modulated
      arc radiotherapy against conventional fixed field IMRT. MATERIALS AND METHODS: CT
      datasets of 10 patients affected by carcinoma of the anal canal were included and
      five plans were generated for each case: fixed beam IMRT, single (RA1)- and
      double (RA2)-modulated arcs with the RapidArc technique. Dose prescription was
      set according to a simultaneous integrated boost strategy to 59.4 Gy to the
      primary tumour PTVI (at 1.8 Gy/fraction) and to 49.5 Gy to risk area including
      inguinal nodes, PTVII. Planning objectives for PTV were minimum dose >95%,
      maximum dose<107%; for organs at risk (OARs): bladder (mean<45 Gy, D(2%)<56 Gy,
      D(30%)<35 Gy), femurs (D(2%)<47 Gy), small bowel (mean<30 Gy, D(2%)<56 Gy). MU
      and delivery time scored treatment efficiency. RESULTS: All techniques fulfilled
      objectives on maximum dose. Some deviations were observed on minimum dose for
      PTV. Uniformity (D(5)-D(95)) on PTVI resulted 6.6+/-1.4% for IMRT and ranged from
      5.7+/-0.3% to 8.1+/-0.8% for RA plans (+/-1 standard deviation). Conformity index
      (CI(95%)) was 1.3+/-0.1 (IMRT) and 1.4+/-0.1 (all RA techniques). Bladder: all
      techniques resulted equivalent above 40 Gy; V(30 Gy) approximately 57% for the
      double arcs, approximately 61% for RA1 and approximately 65% for IMRT. Femurs:
      maximum dose was of the order of 41-42 Gy for all RA plans and approximately 45
      Gy for IMRT. Small bowel: all techniques respected planning objectives. The
      number of computed MU/fraction was 1531+/-206 (IMRT), 468+/-95 (RA1), and 545+/
      80 (RA2) leading to differences in treatment time: 9.4+/-1.7 min for IMRT vs.
      1.1+/-0.0 min for RA1 and 2.6+/-0.0 min for double arcs. CONCLUSION: RapidArc
      showed improvements in organs at risk and healthy tissue sparing with
      uncompromised target coverage when double arcs are applied. Optimal results were
      also achieved anyway with IMRT plans.

PMID- 19181410
TI  - Microbial Responses Viewer (MRV): a new ComBase-derived database of microbial
      responses to food environments.
AB  - ComBase is a large database of microbial responses to food environments and has
      attracted the attention of many researchers and food processors. Although ComBase
      contains a vast amount of data, it is not easy to obtain desired information from
      the retrieved data. In the present study, we developed a new ComBase-derived
      database (Microbial Responses Viewer, MRV) consisting of microbial growth/no
      growth data. The response was defined as representing "growth" if a significant
      increase in bacterial concentration (>1.0 log(10)) was observed. Alternatively,
      "growth" was defined as a positive value of the specific growth rate. The
      growth/no growth data of nineteen different microorganisms were extracted from
      all the data in ComBase comprising 29 kinds of microorganism. Furthermore, the
      specific growth rate of each microorganism was modelled as a function of
      temperature, pH, and water activity (a(w)) using a Poisson log-linear model,
      which is a family of generalized linear models (GLMs). For 16 of the 19
      microorganisms, the specific growth/death rate was successfully modelled as a
      function of temperature, pH, and a(w) using GLM. The specific growth rate was
      illustrated using a two-dimensional contour plot with growth/no growth data. MRV
      provides information concerning growth/no growth boundary conditions and the
      specific growth rates of queried microorganisms. Using MRV, food processors can
      easily find the appropriate food design and processing conditions. This database
      will contribute to the efficient and safe production and distribution of
      processed foods.

PMID- 19181411
TI  - N-starvation stress induced FUM gene expression and fumonisin production is
      mediated via the HOG-type MAPK pathway in Fusarium proliferatum.
AB  - During cultivation of a wild type strain of Fusarium proliferatum on ammonium
      dihydrogen phosphate containing defined medium, expression levels of FUM1 and
      FUM8, members of the fumonisin biosynthesis gene cluster significantly increased
      when ammonium ion concentration of the culture medium decreased below 10 mM,
      indicating that N-depletion triggers the fumonisin biosynthesis genes. Deletion
      of Fphog1, a HOG-type MAP kinase gene resulted in further increases in FUM1 and
      FUM8 expression under nitrogen starvation (absence of any N-source) conditions.
      Fumonisin B1 (FB1) production paralleled with increased FUM gene expression:
      significant amounts of FB1 were measured in culture filtrates of the DeltaFphog1
      deleted mutant after five days culturing, whereas only traces of FB1 could be
      detected in filtrates of the wild type and the restored strain (R1) complemented
      with the wild-type Fphog1-24 gene. N-starvation strongly retarded the growth of
      the DeltaFphog1 mutant in comparison to wild type. The up-regulation of fumonisin
      biosynthesis genes in the DeltaFphog1 mutant could be explained by the increased
      sensitivity of these strains to N-starvation stress that appears in the absence
      of an intact HOG-type MAPK pathway.

PMID- 19181412
TI  - Comparison of adiponectin, leptin and leptin to adiponectin ratio as diagnostic
      marker for metabolic syndrome in older adults of Chinese major cities.
AB  - The aim of this study was to compare the strength of association between
      metabolic syndrome (MetS) and adiponectin, leptin and leptin to adiponectin ratio
      (L/A) in older Chinese. This study included 950 males (220 with MetS) and 1096
      females (452 with MetS), aged 60-96 years from 18 major cities of the 2002 China
      National Nutrition and Health Survey. The associations of adiponectin, leptin and
      L/A with components of MetS and MetS were examined using logistic regression and
      the receiver operating characteristic (ROC) curves. The correlation coefficients
      of MetS components except fasting glucose with leptin were similar to those with
      L/A and higher than those with adiponectin. After adjusting for age and BMI, the
      odds ratio for MetS corresponding to 1 SD change in L/A was higher than those for
      leptin and adiponectin. L/A had highest area under the curve (AUC) for MetS.
      However, there was no statistically significant difference in AUC between leptin
      and L/A, and both indices produced a significantly higher AUC than adiponectin.
      In conclusion, L/A and leptin may be better diagnostic markers for MetS than
      adiponectin. After adjusting for BMI, L/A has better ability for correctly
      classifying subjects with and without MetS than adiponectin or leptin alone.

PMID- 19181413
TI  - Relationship between serum phosphate and cardiovascular risk factors in a large
      cohort of adult outpatients.
AB  - Hyperphosphatemia is associated with an increased risk of cardiovascular
      morbidity and mortality. However, in our large cross-sectional study, high serum
      phosphorus levels were associated with a more favorable profile of traditional
      cardiovascular risk factors, suggesting that hyperphosphatemia may independently
      contribute to the development and progression of cardiovascular disease.

PMID- 19181414
TI  - Experience from a behavioural medicine intervention among poorly controlled adult
      type 1 diabetes patients.
AB  - AIM: To describe experience from a behavioural medicine intervention among poorly
      controlled adult type 1 diabetes patients, in terms of feasibility, predictors
      and associations of improved glycaemic control. METHODS: Data were collected on
      94 poorly controlled adult type 1 diabetes patients who were randomised to a
      study evaluating the effects of a behavioural medicine intervention. Statistics
      covered descriptive and comparison analysis. Backward stepwise regression models
      were used for predictive and agreement analyses involving socio-demographic and
      medical factors, as well as measures of diabetes self-efficacy (DES), diabetes
      locus of control (DLOC), self-care activities (SDSCA), diabetes-related distress
      (Swe-PAID-20), fear of hypoglycaemia (HFS), well-being (WBQ), depression (HAD)
      and perceived stress (PSS). RESULTS: The participation rate in the study was 41%
      and attrition was 24%. Of those patients actually participating in the
      behavioural medicine intervention, 13% withdrew. From the regression models no
      predictors or associations of improvement in HbA(1c) were found. CONCLUSIONS: The
      programme proved to be feasible in terms of design and methods. However, no clear
      pattern was found regarding predictors or associations of improved metabolic
      control as the response to the intervention. Further research in this area is
      called for.

PMID- 19181415
TI  - Role of HNF-1alpha in regulating the expression of genes involved in cellular
      growth and proliferation in pancreatic beta-cells.
AB  - Hepatocyte nuclear factor (HNF)-1alpha is a homeodomain-containing transcription
      factor. Humans heterozygous for mutations in the HNF-1alpha gene develop maturity
      onset diabetes of the young (MODY3), which is associated with reduced insulin
      secretion. The mechanisms responsible for defective glucose-induced insulin
      secretion due to HNF-1alpha deficiency are complex. In order to explore the
      relationship between HNF-1alpha and beta-cell proliferation, we have created a
      novel animal model. Mice lacking one allele of the HNF-1alpha gene were crossed
      with transgenic mice expressing the large T antigen driven by the rat insulin II
      promoter (RIP). The resulting mouse strains allowed us to study the effect of HNF
      1alpha deficiency on the extensive beta-cell proliferation that occurs in these
      mice. Our results indicate that deficiency of HNF-1alpha severely constrains the
      extent of beta-cell proliferation occurring in RIP-Tag mice leading to
      significant changes in blood glucose concentrations as a result of reduced beta
      cell number, insulin content, insulin secretion and intracellular responses in
      Ca(2+). Furthermore expression profiling studies using immortalized cell lines
      generated from HNF-1alpha/RIP-Tag mice showed changes in expression of genes
      involved in cellular growth and proliferation. These results provide insights
      into the mechanisms whereby HNF-1alpha affects beta-cell function.

PMID- 19181416
TI  - Late afternoon blood pressure increase is associated with diabetic retinopathy in
      normotensive type 2 diabetes mellitus patients.
AB  - AIMS: To identify if the variability of blood pressure (BP) is associated with
      diabetic retinopathy (DR) in normotensive type 2 DM patients. METHODS: Sixty-five
      normotensive type 2 DM patients that had 24-h ambulatory BP monitoring (ABPM)
      were grouped according any degree of DR. RESULTS: Fourteen (21%) patients had DR.
      Office BP and 24-h BP parameters did not differ between groups. At late afternoon
      period, patients with DR had higher increment in both systolic (11.3+/-12.7mmHg
      vs. 1.0+/-11.4mmHg, P=0.006) and diastolic (6.7+/-8.6mmHg vs. -0.73+/-10.0mmHg,
      P=0.017) BP levels than those without. Multivariate logistic analyses were
      performed with DR as a dependent variable. Each 1mmHg increment in systolic BP at
      the late afternoon period was associated with a 10.2% increase in DR prevalence
      [OR 1.102 (CI 95% 1.011-1.202, P=0.027)], after adjustments for A1C test, DM
      duration, age, albuminuria and current smoking. CONCLUSIONS: In conclusion, in
      normotensive type 2 DM patients, BP increase at late afternoon is associated to
      DR independently from confounder factors or other ABPM parameters.

PMID- 19181417
TI  - Combined genetic analysis of sputum and computed tomography for noninvasive
      diagnosis of non-small-cell lung cancer.
AB  - CT plays an important role in diagnosis of lung cancer, however has been limited
      by uncertain detection rate for early stage of non-small-cell lung cancer
      (NSCLC), particularly central tumors. Genetic analysis of sputum has proven to be
      useful in diagnosis of NSCLC. We proposed to evaluate efficacy of combing CT and
      genetic analysis of sputum for noninvasive diagnosis of stage I NSCLC. Genomic
      copy changes of a panel of lung cancer-related genes, HYAL2, FHIT, p16, and SP-A
      were analyzed by a mini-chip in sputum from 33 patients with stage I NSCLC and 49
      cancer-free controls. The genetic and CT diagnoses were compared with surgical
      pathologic stage. CT had higher sensitivity (85%) in detection of lung cancer
      compared with the mini-chip (70%) (p<0.05), while there was no significant
      difference in specificity between the two tests (89% vs. 92%, p=0.09). Similarly,
      CT showed considerably higher sensitivity (93%) in identifying peripheral tumors
      than did the mini-chip (64%) (p<0.05), whereas there was no difference in
      specificity between them (98% vs. 96%, p=0.28). However, in detecting central
      tumors, CT had lower specificity (90%) compared with the mini-chip (98%)
      (p<0.05), although its sensitivity (79%) was higher than that of the mini-chip
      (73%) (p=0.05). Combining both tests offered higher sensitivity (91%) than did
      any single one (85%, 70%, all <0.05), while still keeping 92% sensitivity. In
      particular, this combined approach yielded higher sensitivity, specificity, and
      accuracy for diagnosing central cancers compared with CT alone (all p<0.05). The
      integration of the genetic assay with CT led to improvements in noninvasive
      diagnosis of stage I NSCLCs, especially central tumors.

PMID- 19181418
TI  - A psychometric analysis of quality of life tools in lung cancer patients who
      smoke.
AB  - Lung cancer is the leading cause of cancer death for both men and women in the
      United States. Patient quality of life (QOL) prior to cancer treatment is known
      to be a strong predictor of survival and toleration of treatment toxicities. A
      lung cancer patient's self-assessment of QOL is highly valued among clinicians as
      it guides treatment-related decisions and impacts clinical outcomes. Smokers are
      known to report a lower QOL. Limited research has been conducted on QOL outcomes
      in lung cancer patients who continue to smoke. To assess QOL, a reliable and
      valid QOL measure specific to lung cancer is required. The functional assessment
      of cancer therapy-lung cancer (FACT-L) and lung cancer symptom scale (LCSS) are
      instruments that specifically examine QOL among lung cancer patients. The LCSS is
      a focused QOL instrument that includes physical and functional domains of QOL and
      disease symptomatology. The FACT-L is a broader QOL instrument that includes
      physical, functional, social and emotional domains and disease symptomatology.
      Both are psychometrically valid and are widely used in the literature, but have
      not been exclusively evaluated in smokers. Furthermore, there is no 'gold
      standard' instrument since there has never been a correlation study to compare
      estimates of reliability and validity between these instruments. The purpose of
      this study is to report the internal consistency and convergence validity of the
      FACT-L and the LCSS among newly diagnosed lung cancer patients who smoke. This
      data were collected and analyzed from a larger study examining smoking behavior
      among newly diagnosed lung cancer patients (n=51). Descriptive statistics were
      calculated on the FACT-L and LCSS scores, internal consistency was assessed by
      estimating Cronbach's alpha coefficients, and Pearson correlation coefficients
      were estimated between the two scales. Internal consistency coefficients
      demonstrated good reliability for both scales, and the two instruments
      demonstrated a strong correlation, suggesting good convergence validity. Either
      of these instruments are appropriate measures for QOL in lung cancer patients who
      smoke. Given the conceptual difference between the two instruments, it is
      important to carefully consider the research aims when selecting the appropriate
      QOL measurement instrument.

PMID- 19181419
TI  - Parental preferences for boarding locations when a children's hospital exceeds
      capacity.
AB  - STUDY OBJECTIVE: Our objective is to determine parental preferences for boarding
      locations when a children's hospital is at full capacity. We also assess parental
      interest in transfer to a general hospital when a children's hospital is
      experiencing crowding. METHODS: Eligible patients were surveyed within 24 hours
      of admission. Surveys were completed in emergency department (ED) and inpatient
      areas. Previous admission was not required; children with chronic illnesses were
      included. Parents were asked whether they would prefer their child to board in an
      ED hallway or inpatient hallway or whether they had no preference. Parents were
      also asked the maximum acceptable waiting time for an inpatient bed and whether
      they would prefer to be transferred to another hospital should the children's
      hospital not have a bed available. Responses were hypothetical and confidential
      and did not affect care. RESULTS: A total of 382 patients met enrollment criteria
      and 359 (94%) were enrolled; 58.8% (95% confidence interval [CI] 53.5% to 63.9%)
      preferred boarding on inpatient hallways, 11.1% (95% CI 8.2% to 15.0%) preferred
      ED hallways, and 30.1% (95% CI 25.4% to 35.2%) had no preference. Seventy percent
      (95% CI 65.2% to 74.9%) of parents preferred to wait at a children's hospital
      despite crowding. Most parents believed that the maximum acceptable waiting time
      was less than or equal to 3 hours. CONCLUSION: Parents of pediatric patients
      prefer boarding on inpatient hallways over ED hallways. The majority of parents
      prefer to remain at a children's hospital despite crowded conditions, but some
      parents may be amenable to transfer. These results may help institutions develop
      strategies to improve patient satisfaction when hospital capacity is exceeded.

PMID- 19181420
TI  - Massive, fatal, intracardiac thrombosis associated with prothrombin complex
      concentrate.
AB  - Prothrombin complex concentrates are frequently used to rapidly reverse
      anticoagulation with vitamin K antagonists associated with life-threatening
      bleeding. We report a patient receiving warfarin who presented to the emergency
      department with an international normalization ratio greater than 12.8 in cardiac
      tamponade and received prothrombin complex concentrate for rapid reversal of
      anticoagulation. On correction of the tamponade, the patient developed a massive
      and fatal right-sided ventricular thrombus. Thrombogenic complications of
      treatment with prothrombin complex concentrate have been reported before. Caution
      should be used when using prothrombin complex concentrates for reversal of
      anticoagulation.

PMID- 19181421
TI  - Social welfare in the hospital emergency department: the challenge of integrated
      community health care.

PMID- 19181422
TI  - A statewide model program to improve emergency department readiness for pediatric
      care.
AB  - Pediatric emergency patients have unique needs, requiring specialized personnel,
      training, equipment, supplies, and medications. Deficiencies in these areas have
      resulted in historically poorer outcomes for pediatric patients versus adults.
      Since 1985, federally funded Emergency Medical Services for Children (EMSC)
      programs in each state have been working to improve the quality of pediatric
      emergency care. The Health Resources and Services Administration now requires
      that all EMSC grantees report on specific performance measures. This includes
      implementation of a standardized system recognizing hospitals that are able to
      stabilize or manage pediatric medical emergencies and trauma cases. We describe
      the steps involved in implementing Illinois' 3-level facility recognition process
      to illustrate a model that other states might use to provide appropriate
      pediatric care and comply with new Health Resources and Services Administration
      performance measures.

PMID- 19181423
TI  - Eradication of methicillin-resistant Staphylococcus aureus in a neonatal
      intensive care unit: which measures for which success?
AB  - BACKGROUND: Various strategies for controlling methicillin-resistant
      Staphylococcus aureus (MRSA) outbreaks in neonatal intensive care units (NICUs)
      have been tried, with varying levels of success. We report a MRSA outbreak
      occurring between April 2004 and August 2007 in a 24-bed NICU in a large
      university hospital. We describe the difficulties involved in implementing
      measures to control the MRSA outbreak and the possible contribution of each
      measure. METHODS: Cases were defined as neonates with MRSA obtained from either
      clinical cultures or surveillance cultures (from the anterior nares). Systematic
      screening of neonates for colonization was performed only between February and
      December 2005. Successive control strategies included barrier precaution and
      isolation in individual rooms, mupirocine ointment for neonates and health care
      workers, cohort isolation, hand hygiene observation, and staff training. RESULTS:
      During the routine surveillance culture period (February to December 2005; 48
      weeks), 46 neonates were found to be positive for MRSA and were treated with
      mupirocin. After December 2005, the outbreak was controlled, but the ongoing
      spread was not eradicated; 9 sporadic MRSA cases were detected by clinical
      culture up to August 2007. CONCLUSION: The widespread use of mupirocine in staff
      and patients did not control the outbreak and is not recommended. The later
      control appeared to coincide with increased hand hygiene audits and training for
      staff, along with appropriate cohort isolation of neonates and cohort nursing.

PMID- 19181424
TI  - Is isolation of outborn infants required at admission to the neonatal intensive
      care unit?
AB  - BACKGROUND: To measure the rate of colonization of outborn infants with
      methicillin-resistant Staphylococcus aureus (MRSA) to evaluate the need for
      Contact Precautions (including isolation) at the time of admission to the
      neonatal intensive care unit (NICU). METHODS: All 239 consecutive infants
      referred from the neonatal units of other hospitals to a tertiary NICU in Al Ain,
      United Arab Emirates, between January 2000 and December 2007 were screened for
      MRSA colonization. Swabs from the ear, nose, rectum, axillae, and groin were
      obtained from each patient, and the rates of colonization were calculated
      retrospectively. RESULTS: Some 72% of newborns were admitted to our NICU in the
      first week. Only 1 patient, admitted from Oman, grew MRSA from the ear swab
      (rate, 0.4%; 95% confidence interval = 0.01% approximately 2.3%). CONCLUSION:
      This study from a tertiary NICU in a developing country shows that outborn
      infants are unlikely to harbor MRSA, and thus their routine admission in a single
      bed isolation room is not justified. MRSA screening on admission has a very low
      yield and does not appear to be cost-effective. Contact Precautions should be
      reserved for those newborns transferred from general pediatric wards and those
      admitted from home.

PMID- 19181425
TI  - How do Iranian physicians report notifiable diseases? The first report from Iran.
AB  - BACKGROUND: Epidemiologic surveillance through notifiable diseases is an
      essential component of a public health program. Surveillance systems relay mostly
      on physicians to report notifiable diseases The aim of this study was to identify
      physicians' knowledge about reporting of notifiable diseases as well as their
      self-reported practices and perceptions regarding disease reporting barriers and
      ways to improve compliance. METHOD: A validated, reliable self-administered
      questionnaire addressing knowledge of notifiable diseases, self-reported
      practices, reasons for noncompliance with reporting requirements, and suggestions
      to improve compliance with reporting was distributed to 400 general physicians
      (GPs) attending medical conferences in Shiraz, Iran between March and July 2006.
      Knowledge was quantified by evaluating the answers to 45 questions (with 1 point
      awarded for each correct answer). Associations between the independent variables
      and physician knowledge were modeled using analysis of covariance. RESULT: The
      response rate was 75%. The overall mean score was 17.03 +/- 7.45 (range, 4 to
      31). Knowledge of the location of the posted notifiable diseases list was
      positively associated with score on knowledge questions (F = 4.431; P = .036).
      Fully 88% of the participants stated that they had never reported a notifiable
      disease. There was no significant association between the participants' self
      reported practices and knowledge question scores. The major barriers to reporting
      notifiable diseases were the extra time required for reporting and poor knowledge
      of the list of reportable diseases and reporting requirements. The most frequent
      suggestions for improving physicians' compliance with disease reporting were to
      simplify the reporting process and to shift the responsibility for notification
      to another person, such as a secretary or a nurse. CONCLUSION: Our findings
      suggest poor knowledge of disease notification requirements among GPs. Modifying
      physisicans' knowledge and motivation, eliminating barriers to disease reporting,
      and promoting some facilitating factors could help reduce the underreporting of
      notifiable diseases.

PMID- 19181426
TI  - Polymerase chain reaction screening for methicillin-resistant Staphylococcus
      aureus and contact isolation.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections are
      thought to now be endemic in some populations. The early identification of
      individuals admitted to the hospital who are harboring this organism is important
      for the timely implementation of appropriate control strategies. Our objective
      was to measure the prevalence of MRSA carriage in high-risk patients entering our
      hospital and to determine which of these patients screened for MRSA should be
      placed in contact precautions on admission. METHODS: Between January 1, 2007, and
      December 31, 2007, we used polymerase chain reaction analysis, with a turnaround
      time of 4 hours or less, to screen for MRSA in a select group of patients
      entering our hospital. RESULTS: We screened 1,568 patients and found 144 (9.2%)
      positive. Of the 1,568 patients, 170 (10.8%) were known to previously have been
      MRSA positive. Of these, 90 (52.9%) had negative screens. CONCLUSION: We used a
      rapid screening test to identify patients harboring MRSA. Our findings support
      that MRSA is harbored sporadically and patients do not have to be placed in
      contact isolation based on a history of previously being MRSA positive.

PMID- 19181428
TI  - Can the emotion of disgust be harnessed to promote hand hygiene? Experimental and
      field-based tests.
AB  - Two studies carried out in Sydney, Australia explored whether inducing disgust
      may be a useful addition to hand-hygiene interventions. Experiment 1 employed a
      novel laboratory measure of hand hygiene, and tested whether a brief (3-min)
      video-based intervention using disgust/education, improved hand hygiene relative
      to education alone and a control condition. On test, a week later, the disgust
      intervention significantly exceeded the education and control condition combined,
      although the effect size was modest. Experiment 2 examined the generality of this
      effect in a field study. During a baseline period, soap and paper towel use in a
      series of washrooms were covertly monitored. This was followed by an intervention
      period, in which two washrooms received disgust/education-based posters and a
      further two, educational posters, exhorting participants to wash their hands. A
      follow-up period, after the posters were removed, was also monitored. The disgust
      based intervention was significantly better at promoting hand hygiene. These
      findings suggest that even brief disgust-based interventions may be successful
      and that these can be tested and developed under laboratory conditions.

PMID- 19181427
TI  - Molecular surveillance of methicillin-susceptible Staphylococcus aureus at a
      neonatal intensive care unit in Brazil.
AB  - BACKGROUND: We evaluated the relationship among hospital infection and
      colonization by methicillin-susceptible Staphylococcus aureus (MSSA), clonal
      spread, and associated risk factors in a neonatal intensive care unit (NICU) of
      the Uberlandia Federal University-affiliated hospital in Brazil. METHODS: Between
      February 2004 and June 2005, a longitudinal surveillance study was carried out in
      an NICU with neonates presenting infections, through both the NNIS system and S
      aureus punctual colonization prevalence inquests. RESULTS: The overall rate of
      infection incidence was 23/1000 patient-days. Of all the neonates assessed, 15
      were infected and 15 colonized. Sepsis was the most frequent infection, whereas
      anterior nare was the most isolated site. Antibiotics use, central vascular
      catheter (CVC), and CVC use more than 7 days and its insertion by phlebotomy were
      the risk factors for colonization/infection. Molecular analysis showed polyclonal
      origin (12 genotypes), with predominance of a genotype ("B"), and clonal identity
      between colonization and infection samples. CONCLUSION: The analysis by means of
      classical epidemiology and molecular techniques pointed out that methicillin
      susceptible Staphylococcus aureus infections were associated with previous
      colonization by the pathogen, with evidence of horizontal transmission within the
      unit.

PMID- 19181429
TI  - Fatigue behaviour of dental composite materials.
AB  - OBJECTIVE: The intent of the project was to evaluate the fatigue behavior of
      particle and fiber filled dental composites that are fabricated either directly
      or indirectly using a notched specimen with respect to the number of cycles until
      failure. METHODS: The materials were five dental composites, three normally cured
      in the oral cavity (Restolux, Renew and Filtek Supreme), direct processing, and
      two laboratory produced (BelleGlass, and Tescera), indirect processing. The
      specimens were 3mmx3mmx25mm bars with a 0.75 or 1.0mm notch in the mid-span of
      the bars, polished with 320 grit SiC paper and aged for 6 months in air,
      distilled water, artificial saliva, and a 50/50 mixture of ethanol and distilled
      water. Testing was performed with a stress mean range of 5-49MPa, the maximum
      number of cycles was 100,000, and the number of cycles to failure was recorded.
      RESULTS: For the specimens that failed, BelleGlass, Restolux, and Tescera were
      able to withstand a higher cyclic loaded stress than Renew and Filtek. The 50/50
      by volume mixture of water and ethanol resulted in the lowest resistance to
      fatigue for all materials. CONCLUSIONS: Of the dental composite materials
      investigated, the indirect processed and those with large particle fillers
      (higher weight percent filler) had better cyclic fatigue resistance than micro-
      and nano-particle fillers (lower weight percent filler).

PMID- 19181430
TI  - Effects of BLS training on factors associated with attitude toward CPR in college
      students.
AB  - AIM: In order to elucidate the factors for willingness to perform CPR, we
      evaluated the responses of college students to questionnaires before and after
      basic life support (BLS) training. METHODS: Before and after participating in a
      small group BLS course, 259 students completed questionnaires. A logistic
      regression model was used to elucidate independent factors for their willingness
      to attempt resuscitation. RESULTS: Factors associated with willingness to perform
      BLS for strangers were "anxiety for a bad outcome" (odds ratio (OR) 0.08) and
      "having knowledge of automated external defibrillator (AED)" (OR 4.5) before
      training. The proportion of students showing willingness to perform BLS increased
      from 13% to 77% after the training even when the collapsed person is a stranger.
      After training, "anxiety for being sued because of a bad outcome" (OR 0.3), and
      "anxiety for infection" (OR 3.8) were significant factors. Those who preferred to
      perform BLS without ventilation increased from 40% to 79% (p<0.0001). CONCLUSION:
      The proportion of students showing willingness to perform BLS increased after the
      training. Significant association between "anxiety for infection" and willingness
      to perform BLS might indicate that those who wish to perform BLS developed their
      awareness of risk of infection more than the counterparts. For future guidelines
      for resuscitation and the instruction consensus, the reluctance of bystanders to
      perform CPR due to the hesitation about mouth-to-mouth ventilation should be
      reconsidered with other recent reports indicating the advantage of compression
      only CPR.

PMID- 19181432
TI  - A potential role for adrenal androgens in postpartum psychiatric distress.

PMID- 19181433
TI  - A 3-year follow-up of women with endometriosis and pelvic pain users of the
      levonorgestrel-releasing intrauterine system.

PMID- 19181434
TI  - Methotrexate induces apoptosis of human choriocarcinoma cell line JAR via a
      mitochondrial pathway.
AB  - OBJECTIVE: To investigate methotrexate (MTX)-induced apoptosis and the involved
      pathways in human choriocarcinoma cells. STUDY DESIGN: MTX-induced apoptosis of
      human choriocarcinoma cell line JAR was examined using a PI/Annexin V stain with
      flow cytometer (FCM). Mitochondrial apoptosis was detected by fluorescence
      microscopy, and analyzed by FCM using a MitoCapture mitochondrial apoptosis
      detection kit. The activities of caspase-8 and caspase-9 were quantified by
      microtiter plate reader at 405 nm using FLICE/Caspase-8 colorimetric assay kit
      and Caspase-9/Mch6 colorimetric assay kit. The changes in Bax and Bcl-2
      expression were detected during apoptosis using immunocytochemistry and Western
      blot analysis. RESULTS: JAR cells underwent apoptosis after exposure to 0.1-2.5
      microg/ml MTX for 48 h. Decreased mitochondrial membrane potential was observed
      both by fluorescence microscopy and FCM. The activation of caspase-9 was
      increased 4.35+/-0.76-fold in MTX-incubated JAR, while there was no obvious
      change in the activation of caspase-8. When JAR cells underwent apoptosis, the
      expression of Bcl-2 was decreased and the expression of Bax was increased; both
      were detected by immunocytochemistry assay. CONCLUSION: Methotrexate in lower
      concentrations induces apoptosis of human choriocarcinoma cells via mitochondrial
      initiated pathways, including reduction of mitochondrial membrane potential,
      activation of caspase-9, and up-regulation of Bax/Bcl-2 expression.

PMID- 19181435
TI  - The safety of quinolones--a meta-analysis of pregnancy outcomes.
AB  - OBJECTIVE: We conducted a meta-analysis of all published data in order to
      evaluate the risk for birth defects, stillbirths, preterm births and low birth
      weight following exposure to quinolones in the first trimester of pregnancy.
      STUDY DESIGN: Medline, Embase, Scopus, Biological Abstracts and Proquest Thesis
      Dissertation databases were searched. Other papers and abstracts were located
      from the retrieved articles' references, meeting booklets, internet web sites and
      books on teratology. RESULTS: Five studies met the inclusion criteria. The
      summary odds ratio for all the included studies was 1.05 (95% CI 0.90-1.22) for
      major malformations, 2.6 (95% CI 0.36-18.67) for stillbirths, 1.15 (95% CI 0.69
      1.91) for preterm births and 0.73 (95% CI 0.30-1.79) for low birth weight. In an
      additional analysis including only fluoroquinolones (nalidixic acid was removed),
      the summary odds ratio for major malformations remained non-significant (1.11,
      95% CI 0.57-2.15). CONCLUSIONS: The use of quinolones during the first trimester
      of pregnancy does not appear to represent an increased risk for major
      malformations recognized after birth, stillbirths, preterm births or low birth
      weight.

PMID- 19181436
TI  - Initial experience with a short, tension-free vaginal tape (the tension-free
      vaginal tape secur system).
AB  - OBJECTIVE: The aim of this study is to present our first experience with a novel
      modification of the tension-free sling idea and to evaluate the safety and
      efficacy of this new procedure for the treatment of stress urinary incontinence
      in women. STUDY DESIGN: Eighty-five women with previously untreated stress
      urinary incontinence were recruited to participate in a clinical study. The
      efficacy of this surgical procedure was evaluated perioperatively and 3 months
      (+/-1 week) after operation--objectively by cough test and subjectively by the
      questionnaires Pelvic Organ Prolapse/Urinary Incontinence Sexual Function
      Questionnaire and the International Consultation on Incontinence Questionnaire
      Short Form. All data were processed and statistical analyses performed in
      statistical environment R, version 2.5.1. RESULTS: From our results we conclude
      that there were no perioperative complications, objectively 62% of these patients
      were completely dry and 25% of patients improved. We observed a higher proportion
      of vaginal wall erosion (7/85) and urgency de novo (5/85) in the learning period
      group with respect to the routine period group. CONCLUSIONS: Our first experience
      with the tension-free vaginal tape secur system procedure is that it has a low
      percentage of perioperative complications. The learning curve has to be taken in
      account with reference to postoperative complications.

PMID- 19181437
TI  - Differential chemical and thermal unfolding pattern of Rv3588c and Rv1284 of
      Mycobacterium tuberculosis - A comparison by fluorescence and circular dichroism
      spectroscopy.
AB  - The thermal and chemical unfolding pathways of two beta carbonic anhydrases,
      Rv3588c and Rv1284 of Mycobacterium tuberculosis have been compared by
      fluorescence and circular dichroism. Chemical and thermal denaturation of the
      tertiary and secondary structures of these two ubiquitous enzymes of the pathogen
      reveals that the unfolding of Rv3588c is mediated through the formation of a
      molten globule intermediate with depleted tertiary structure. However, Rv1284
      directly unfolds from the native to the unfolded state. Calculation of the
      thermodynamic parameters suggest that overall Rv3588c is more stable than Rv1284.
      Stern-Volmer analysis together with the fluorescence spectra of the proteins
      suggest that Trp115 in Rv1284 is more buried than Trp10 in Rv3588c. The
      tryptophan residues in both the proteins are surrounded by positively charged
      amino acid residues.

PMID- 19181438
TI  - Review of pollutants removed by electrocoagulation and
      electrocoagulation/flotation processes.
AB  - The word "electrocoagulation" (EC) will be sometimes used with "electroflotation"
      (EF) and can be considered as the electrocoagulation/flotation (ECF) process.
      Through the process of electrolysis, coagulating agents such as metal hydroxides
      are produced. When aluminium electrodes are used, the aluminium dissolves at the
      anode and hydrogen gas is released at the cathode. The coagulating agent combines
      with the pollutants to form large size flocs. As the bubbles rise to the top of
      the tank they adhere to particles suspended in the water and float them to the
      surface. In fact, a conceptual framework of the overall ECF process is linked to
      coagulant generation, pollutant aggregation, and pollutant removal by flotation
      and settling when it has been applied efficiently to various water and wastewater
      treatment processes. This review paper considers a significant number of common
      applications of EC and ECF processes which have been published in journal and
      conference papers.

PMID- 19181439
TI  - Seizure control and side-effect profile after switching adult epileptic patients
      from standard to extended-release divalproex sodium.
AB  - OBJECTIVES: To assess changes in seizure frequency, medication side-effects
      (especially tremor) and formulation preference after switching patients overnight
      from immediate-release to extended-release divalproex sodium. METHODS:
      Prospective evaluation of consecutive adult outpatients at an urban public
      hospital who were followed for 6 months after switching drug formulations.
      Seizure frequency was estimated from patient self-reports. Medication side
      effects were monitored with a structured interview (tremor, fatigue, GI upset,
      hair loss), physician exam (nystagmus, tremor), a drawing test (tremor) and a
      specific 25-item questionnaire assessing the impact of tremor on activities of
      daily living. RESULTS: Forty-seven patients were included in the study but six
      patients were either lost to follow-up or had insufficient data. Seizure
      frequency and side-effect profile did not change significantly after switching
      drug formulations. However, patients had significant subjective improvement in
      their tremor with the extended-release formulation as assessed by the 25-item
      questionnaire (p=0.009 at 3 months and p=0.04 at 6 months); other measures of
      tremor severity showed no change during the 6-month follow-up period. Most
      patients (71%) preferred the extended-release formulation. CONCLUSION: Patients
      with epilepsy can be switched overnight from standard to extended-release
      divalproex sodium, without significant change in seizure frequency and drug side
      effect profile. Most patients prefer the extended-release formulation, in part
      due to subjective decrease in tremor during daily activities.

PMID- 19181440
TI  - Does botulinum toxin injection in parotid glands interfere with the swallowing
      dynamics of Parkinson's disease patients?
AB  - BACKGROUND: During recent years, sialorrhea in Parkinson's disease (PD) has been
      treated with botulinum toxin type A (BT-A); however, there are no data describing
      its effects on swallowing dynamics in this group of patients. OBJECTIVE: To
      investigate whether injection of BT-A into the parotid glands interferes with the
      oropharyngeal swallowing dynamics of patients with Parkinson's disease. METHODS:
      Sixteen patients with diurnal sialorrhea were selected and evaluated during the
      "on" period by a standardized questionnaire and swallowing videofluoroscopy
      before and 30 days after ultrasound-guided BT-A injection into the parotid
      glands. RESULTS: A decrease in sialorrhea was observed in all studied patients.
      Silent laryngeal penetration was observed in three patients, and silent
      aspiration was observed in two of them. There were no changes in swallowing
      dynamics when comparing patients before and after BT-A parotid injection (p=1),
      suggesting similar levels of dysphagia in the two measurements. CONCLUSION: BT-A
      injection into parotid glands does not interfere with the oropharyngeal
      swallowing dynamics of PD patients.

PMID- 19181441
TI  - Overexpression of follicle-stimulating hormone receptor facilitates the
      development of ovarian epithelial cancer.
AB  - We previously showed that the expressing level of FSH receptor (FSHR) increased
      from ovarian epithelial inclusions (OEIs) to benign ovarian epithelial tumors
      (OETs) and to borderline OETs, whereas FSHR levels decreased with an increase in
      carcinoma grade. The aim of this study was to investigate the role of FSHR in OET
      development. MCV152 cells with FSHR overexpression showed an increased cellular
      proliferation and invasive capacity, which was associated with reduced levels of
      prohibitin and RII-beta expression and increased levels of HER-2/neu, c-Myc, and
      EGFR expression. Overexpression of FSHR may be associated with an elevated level
      of OET cell proliferation via an enhanced activity of potential oncogenic
      pathways. Therefore, the findings in this study suggest that overexpression of
      FSHR may play a role in OET development.

PMID- 19181442
TI  - Development of vorinostat: current applications and future perspectives for
      cancer therapy.
AB  - Vorinostat is a potent histone deacetylase inhibitor that blocks the catalytic
      site of these enzymes. A large number of cellular proteins are modified post
      translationally by acetylation, leading to altered structure and/or function.
      Many of these proteins, such as core nucleosomal histones and transcription
      factors, function in key cellular processes and signal transduction pathways that
      regulate cell growth, migration, and differentiation. At concentrations that are
      non-toxic to normal cells, vorinostat dramatically alters cellular acetylation
      patterns and causes growth arrest and death and in a wide range of transformed
      cells, both in vitro and in animal tumor models. Vorinostat has shown promising
      clinical activity against hematologic and solid tumors at doses that have been
      well tolerated by patients. Recent non-clinical experiments that explored the
      effects of vorinostat in combination with other chemotherapeutic agents have
      begun to illuminate potential mechanisms of action for this histone deacetylase
      inhibitor and are providing guidance for new avenues of clinical investigation.

PMID- 19181443
TI  - Benzo[a]pyrene promotes proliferation of human lung cancer cells by accelerating
      the epidermal growth factor receptor signaling pathway.
AB  - Smoking is an independent prognostic factor of lung adenocarcinoma.
      Benzo[a]pyrene (B[a]P) is one of the strongest carcinogens and it is present in
      both the environment and cigarette smoke. In this study, the effect of B[a]P on
      the proliferative activity of lung adenocarcinoma cells was investigated. A lung
      adenocarcinoma cell line, A549, was cultured with B[a]P for various periods, and
      its proliferative activity was examined by an MTS assay. To investigate the
      intracellular events related to the proliferative activity, the gene expression
      profile was investigated by a microarray analysis and a quantitative RT-PCR, and
      the protein expression and activation status of Akt, ERK 1/2 and the epidermal
      growth factor receptor (EGFR) were examined by a western blot analysis. Following
      the culture with B[a]P for 24 weeks, the serum-independent proliferative activity
      was increased. A microarray analysis revealed that a reversible upregulation of
      the EGFR and epiregulin genes was recognized in the B[a]P treated cells, in which
      the overexpression of the phosphorylated EGFR protein was also recognized. The
      EGFR tyrosine kinase inhibitor reduced the cellular proliferation and the level
      of phosphorylation of ERK1/2, which is a downstream signal of the EGFR, in the
      B[a]P-treated A549 cells. Moreover, the B[a]P treatment increased the mRNA
      expressions of the ligands for EGFR such as amphiregulin and epiregulin. B[a]P
      increases the proliferative potential of lung adenocarcinoma cells through the
      EGFR signaling pathway.

PMID- 19181444
TI  - Carrier element-free coprecipitation with 3-phenly-4-o-hydroxybenzylidenamino-4,5
      dihydro-1,2,4-triazole-5-one for separation/preconcentration of Cr(III), Fe(III),
      Pb(II) and Zn(II) from aqueous solutions.
AB  - A separation/preconcentration procedure, based on the coprecipitation of Cr(3+),
      Fe(3+), Pb(2+) and Zn(2+) ions using a new organic coprecipitant, 3-phenly-4-o
      hydroxybenzylidenamino-4,5-dihydro-1,2,4-triazole-5-one (POHBAT) without adding
      any carrier element has been developed. The method, thus, has been called carrier
      element-free coprecipitation (CEFC). The resultant concentrated elements were
      determined by flame atomic absorption spectrometric determinations. The
      influences of some analytical parameters including pH of the solution, amount of
      the coprecipitant, standing time, centrifugation rate and time, sample volume and
      diverse ions were investigated on the quantitative recoveries of analyte ions.
      The validation of the present preconcentration procedure was performed by the
      analysis of two certified reference materials. The recoveries of understudy
      analytes were found in the range of 93-98%, while the detection limits were
      calculated in the range of 0.3-2.0 microg L(-1). The precision of the method
      evaluated as relative standard deviation (R.S.D.), was in the range of 3-7%
      depend on the analytes. The proposed method was successfully applied to
      environmental samples for the determination of the analytes.

PMID- 19181445
TI  - Removal of mercury from water by carbonaceous sorbents derived from walnut shell.
AB  - The adsorption ability of a powdered activated carbon (PAC) derived from walnut
      shell was investigated in an attempt to produce more economic and effective
      sorbent for the control of Hg(II) ion from industrial liquid streams.
      Carbonaceous sorbents derived from Iranian walnut shell (WS) were prepared by
      chemical activation method using ZnCl(2) as an activating reagent. To the best of
      our knowledge, this adsorbent was not used before for removing mercury from
      water. Adsorption of Hg(II) from aqueous solutions was carried out under
      different experimental conditions by varying treatment time, metal ion
      concentration, adsorbent amount, pH and solution temperature. It was determined
      that Hg(II) adsorption follows both Langmuir and Freundlich isotherms as well as
      pseudo-second-order kinetics. It was also shown that Hg(II) uptake decreases with
      increasing pH of the solution. The proper choice of preparation conditions
      resulted in a microporous activated carbon with 0.45 g/cm(3) density, 737 mg/g
      iodine number and 780 m(2)/g BET surface area. The monolayer sorption capacity of
      this optimum adsorbent was obtained as 151.5 mg/g.

PMID- 19181446
TI  - Lethal and teratogenic effects of phenol on Bufo arenarum embryos.
AB  - Phenol and their derivatives are used in several industries and they have a high
      potential toxicity for animal and plant species. They were found in variable
      concentrations, as high as 1000 mg/L, in industrial wastewater and, they are
      often discharged into the environment. Amphibian embryos are useful indicators of
      environmental pollution. However, to our knowledge, there are not studies
      focussed on the toxic effects of phenol on Bufo arenarum, which is an anuran
      widely distributed in South America. Therefore, the effect of phenol on the
      survival and morphogenesis of these amphibian embryos was evaluated by means of
      AMPHITOX test. Embryos at 25 stage of development (acute test) and embryos at 2-4
      blastomers stage (early life stage test), were exposed to phenol solutions in
      concentrations ranging from 25 to 250 mg/L, which were frequently found in the
      environment. Mortality and malformations were registered each 24h. LC(50),
      LC(99), NOEC, TC(50) and TI(50) values were 183.70, 250, 60, 113 mg/L and 1.62,
      respectively, at 96 h of treatment. Mortality and the percentage of malformations
      increased with increasing phenol concentrations. Teratogenic effects more
      frequently produced by phenol were: axial flexure, persistent yolk plug and
      different abnormalities which caused death of blastulae. Moreover, other
      malformations were registered, such as irregular form, acephalism, edema, axial
      shortening and underdevelopment of gills, among others. Larvae of B. arenarum, at
      early embryonic stages (blastulae), showed higher sensitivity to phenol than
      tadpoles at stage 25. Results confirm high susceptibility of amphibians to phenol
      and that environmental concentrations of this pollutant might be harmful to these
      populations.

PMID- 19181447
TI  - Agricultural based activated carbons for the removal of dyes from aqueous
      solutions: a review.
AB  - This review evaluates a number of different agricultural waste adsorbents and
      types of dyes. Certain wastewater containing different dye contaminants causes
      serious environmental problems. Recently, growing research interest in the
      production of carbon based has been focused on agricultural by-products. Low cost
      adsorbents derived from agricultural wastes have demonstrated outstanding
      capabilities for the removal of dyes from wastewater. Therefore, low cost
      agricultural waste adsorbents can be viable alternatives to activated carbon for
      the treatment of contaminated wastewater. The use of cheap and eco-friendly
      adsorbents have been studied as an alternative substitution of activated carbon
      for the removal dyes from wastewater. The dye adsorption capacities of
      agricultural waste adsorbents vary, depending on the characteristics of the
      individual adsorbent, the extent of surface modification and the initial
      concentration of adsorbate.

PMID- 19181448
TI  - Opioid therapy for nonspecific low back pain and the outcome of chronic work
      loss.
AB  - Outcomes of opioid therapy for noncancer pain remain to be more fully explored.
      Loss of work is among these outcomes. Especially when work loss becomes "chronic"
      (persists >or=90 days), it has profound psycho-social repercussions that compound
      suffering of those already in pain. Furthermore, costs escalate as work loss
      persists. We thus explored associations between opioid therapy for back pain and
      chronic work loss. Data consisted of workers compensation claims for nonspecific
      low back pain. We used multivariate analyses to control for diverse covariates.
      Workers with no opioid prescriptions constituted the reference group. Findings
      included the following: compared with the (no opioid) reference group, odds of
      chronic work loss were six times greater for claimants with schedule II
      ("strong") opioids; compared with the reference group, odds of chronic work loss
      were 11-14 times greater for claimants with opioid prescriptions of any type
      during a period of >or=90 days; and three years after injury, costs of claimants
      with schedule II opioids averaged $19,453 higher than costs of claimants in the
      reference group. Our analysis was not designed to ascertain antecedent causes, or
      why chronic work loss occurred in the first place. Rather, we focused on an
      ensuing consequence of opioid therapy, i.e., the outcome of chronic work loss,
      which occurred far removed in time (>or=90 days) after the worker's recorded date
      of back injury. The strong associations observed suggest that for most workers
      opioid therapy did not arrest the cycle of work loss and pain.

PMID- 19181449
TI  - What causes low back pain?

PMID- 19181450
TI  - Toxoplasma gondii and Neospora caninum antibodies in sheep in the Czech Republic.
AB  - In the Czech Republic, serum from 547 sheep coming from nine farms was examined
      for antibodies against parasites Toxoplasma gondii and Neospora caninum by
      screening ELISA. Antibodies against T. gondii were found in 325 sheep (59%) with
      prevalence ranging from 11% to 96% in different farms. Antibodies against N.
      caninum were found in 63 sheep (12%) with prevalence ranging from 4% to 21% in
      different farms. Mixed infections were found in 53 sheep (10%). It was the first
      evidence of N. caninum antibodies in sheep from the Czech Republic.

PMID- 19181451
TI  - Dysfunction of the hypothalamic-pituitary-adrenal axis and functional somatic
      symptoms: a longitudinal cohort study in the general population.
AB  - In persons with functional somatic symptoms (FSS), no conventionally defined
      organic pathology is apparent. It has been suggested that complex interactions of
      psychological, physiological, and social factors are involved in the etiology of
      FSS. One of the physiological mechanisms that may contribute to FSS is the
      function of the hypothalamic-pituitary-adrenal (HPA)-axis. This study
      investigates the association of HPA-axis function with cross-sectional presence
      and prospective development of FSS in the general population. This study was
      performed in a population-based cohort of 741 male and female adults (mean age
      53.1, S.D. 10.9). Participants completed the somatization section of the
      Composite International Diagnostic Interview (CIDI) in which the presence of 43
      FSS is surveyed. In addition to the total number of FSS, bodily system FSS
      clusters with musculoskeletal, gastrointestinal, cardiorespiratory, and general
      symptoms were constructed. HPA-axis function was assessed by measuring 24-h
      urinary free cortisol (24-h UFC) excretion. Follow-up measurements were performed
      approximately 2 years later. All analyses were adjusted for age, gender, body
      mass index, smoking, alcohol use, depression, exercise frequency, and urinary
      volume. Regression analysis detected no cross-sectional association between 24-h
      UFC excretion and the number of FSS (beta=-0.021, t=-0.521, p=0.603). In
      addition, 24-h UFC excretion was not associated with any of the bodily system FSS
      clusters (all p>0.050). Furthermore, 24-h UFC excretion did not predict new-onset
      FSS in the 2-year follow-up period (beta=0.021, t=0.566, p=0.572). We conclude
      that this study does not provide evidence for an association between altered HPA
      axis function, as indexed by 24-h UFC, and FSS in the general population. We
      conclude that this study does not provide evidence for an association between
      altered HPA-axis function, as indexed by 24-h UFC, and FSS in the general
      population.

PMID- 19181452
TI  - Quality of life in congenital, untreated, lifetime isolated growth hormone
      deficiency.
AB  - Impaired quality of life (QoL) is commonly described as being associated with
      growth hormone (GH) deficiency (GHD), and beneficial effects of GH replacement
      therapy on QoL have been reported. However, most studies examined heterogeneous
      cohorts of patients GHD of varying etiologies, severities and age of onset. Most
      of these patients miss other pituitary hormones, whose replacement can also
      influence QoL. We studied the QoL of a homogeneous cohort of 20 adults with
      isolated GH deficiency (IGHD) due to the same mutation in the GH-releasing
      hormone receptor gene (IGHD, 10 men) using the Life Satisfaction Hypopituitarism
      Module (QLS-H), and compared them with 20 matched controls residing in the same
      community (CO, 10 men). Additionally, the IGHD group was evaluated after 6 months
      of treatment with bi-monthly depot GH, and after 12 months from its interruption.
      There was no difference in the total score of QoL (TSQoL) or in any of the nine
      categories that composes the questionnaire between IGHD and CO. Similar results
      were obtained when data were analyzed by sex. GH treatment only increased
      satisfaction with physical endurance, but did not cause an increase in the TSQoL.
      We conclude that in this unique population congenital, untreated, lifetime IGHD
      does not reduce QoL, and treatment with GH for 6 months only causes improvement
      in satisfaction with physical resistance.

PMID- 19181453
TI  - Pre-pubertal stress exposure affects adult behavioral response in association
      with changes in circulating corticosterone and brain-derived neurotrophic factor.
AB  - Early-life stress produces a cascade of neurobiological events that cause
      enduring changes in neural plasticity and synaptic efficacy that appear to play
      pivotal roles in the pathophysiology of post-traumatic stress disorder (PTSD).
      Brain-derived neurotrophic factor (BDNF) has been implicated in the
      neurobiological mechanisms of these changes, in interaction with components of
      the stress response, such as corticosterone. This study examined the consequences
      of juvenile stress for behavior during adulthood in association with circulating
      corticosterone levels and BDNF expression. The experiments examined single
      exposure to predator scent stress (soiled cat litter for 10 min) as compared to
      repeated exposure, early in life and later on. Behavioral responses were assessed
      in the elevated plus maze and the acoustic startle response paradigms at 28, 60
      and 90 days of age. Plasma corticosterone was measured and brain areas analyzed
      for BDNF levels. The results show that juvenile stress exposure increased anxiety
      like behavior and startle amplitude and decreased plasma corticosterone. This
      response was seen immediately after exposure and also long term. Adult stress
      exposure increased anxiety-like behavior, startle amplitude and plasma
      corticosterone. Exposure to both early and later life trauma elicited reduced
      levels of corticosterone following the initial exposure, which were not raised by
      re-exposure, and elicited significant downregulation of BDNF mRNA and protein
      levels in the hippocampus CA1 subregion. The consequences of adult stress
      exposure were more severe in rats were exposed to the same stressor as juveniles,
      indicated increased vulnerability. The results suggest that juvenile stress has
      resounding effects in adulthood reflected in behavioral responses. The
      concomitant changes in BDNF and corticosterone levels may mediate the changes in
      neural plasticity and synaptic functioning underlying clinical manifestations of
      PTSD.

PMID- 19181455
TI  - AMP-activated kinase may suppress NADPH oxidase activation in vascular tissues.
AB  - Activation of AMP-activated kinase (AMPK) suppresses NF-kappaB-mediated
      transcription in endothelial cells exposed to palmitate or TNF-alpha; it also
      impedes angiotensin II-driven proliferation in vascular smooth muscle cells.
      These phenomena become predictable if we postulate that AMPK can inhibit
      activation of NADPH oxidase. Such an effect would make sense from a homeostatic
      perspective, and moreover there is direct evidence that AMPK suppresses NADPH
      oxidase activation in neutrophils. New evidence that sub-pathological levels of
      peroxynitrite can activate AMPK suggest that this enzyme may act as an "early
      warning signal" for oxidant stress; inhibiting NADPH oxidase would constitute a
      rational feedback response to such a signal.

PMID- 19181454
TI  - Chronic stress increases pituitary adenylate cyclase-activating peptide (PACAP)
      and brain-derived neurotrophic factor (BDNF) mRNA expression in the bed nucleus
      of the stria terminalis (BNST): roles for PACAP in anxiety-like behavior.
AB  - Exposure to chronic stress has been argued to produce maladaptive anxiety-like
      behavioral states, and many of the brain regions associated with stressor
      responding also mediate anxiety-like behavior. Pituitary adenylate cyclase
      activating polypeptide (PACAP) and its specific G protein-coupled PAC(1) receptor
      have been associated with many of these stress- and anxiety-associated brain
      regions, and signaling via this peptidergic system may facilitate the
      neuroplasticity associated with pathological affective states. Here we
      investigated whether chronic stress increased transcript expression for PACAP,
      PAC(1) receptor, brain-derived neurotrophic factor (BDNF), and tyrosine receptor
      kinase B (TrkB) in several nuclei. In rats exposed to a 7 days chronic variate
      stress paradigm, chronic stress enhanced baseline startle responding induced by
      handling and exposure to bright lights. Following chronic stress, quantitative
      transcript assessments of brain regions demonstrated dramatic increases in PACAP
      and PAC(1) receptor, BDNF, and TrkB receptor mRNA expression selectively in the
      dorsal aspect of the anterolateral bed nucleus of the stria terminalis (dBNST).
      Related vasoactive intestinal peptide (VIP) and VPAC receptor, and other stress
      peptide transcript levels were not altered compared to controls. Moreover, acute
      PACAP38 infusion into the dBNST resulted in a robust dose-dependent anxiogenic
      response on baseline startle responding that persisted for 7 days. PACAP/PAC(1)
      receptor signaling has established trophic functions and its coordinate effects
      with chronic stress-induced dBNST BDNF and TrkB transcript expression may
      underlie the maladaptive BNST remodeling and plasticity associated with anxiety
      like behavior.

PMID- 19181456
TI  - Pursuing treatments that are not evidence based: how DSM IV clarifies, how it
      blinds psychiatrists to issues in need of investigation.
AB  - Evidence based medicine claims to be the paradigm for modern psychiatry. It
      represents proven treatments for defined diagnoses. But there are major problems
      with this position, starting with the fact that while they are superior to
      placebo, evidence based treatments too often are ineffective. It cannot be
      assumed that classifying psychopathology diagnostically is the best way to move
      forward. Established diagnostic entities, are as much wish as reality. They are
      the result of committee decisions so tentative that DSM III and IV refuse to use
      the term "diagnoses" in the diagnostic manual. There is also a more fundamental
      issue, not answerable to the vote of even the most "expert" committee. What do
      diagnoses represent? Does every diagnosis in DSM IV represent an actual real
      illness, in the sense that polio, cancer, or a strept throat actually exist? Or
      can they represent the reification of an idea, taking diagnoses beyond useful
      limits? Evidence based medicine, it is implied, should monopolize clinical
      approaches. But at this stage the proper question is not should we exclusively
      use treatments that have proven superior to placebo? It is what is the best way
      to formulate treatment strategies when now, and in the foreseeable future,
      science cannot offer answers that we need? Conjecture, out of necessity, must
      play a significant role. Given mediocre treatment results, we need all the help
      we can get, the art of psychiatry as well as the science. Pharmacological agents
      can be viewed as inducing particular psychological states which, though not
      specifically related to diagnosis, are nonetheless the basis for their
      usefulness. SSRIs are efficacious in a broad range of conditions because
      increasing serotonin has a psychological impact that is nonspecific to the
      disorders. It can be used in treatment contexts when diagnosis is irrelevant
      (e.g. helping a picked on, thin skinned adolescent, develop thicker skin). The
      core issue is our approach to patients. Evidence based medicine eschews the
      anecdotal in the name of generalized conclusions, based on the odds that the
      patient's ailments are typical for their group. This is not a ridiculous
      consideration, but it can miss important particulars brought by the patient.
      Knowing a patient well can be the difference between effective and ineffective
      treatment. Premorbid defenses, character style, the nature of the patients'
      stressors, their story can guide clinicians to a particular medication, and
      influence dosage. While evidence based medicine has a place, especially when low
      cost is a consideration, it cannot lay claim to being optimal treatment. It is
      especially detrimental if this perspective acts like blinders, obscuring more
      than it clarifies.

PMID- 19181458
TI  - Predictors of injection drug use cessation and relapse in a prospective cohort of
      young injection drug users in San Francisco, CA (UFO Study).
AB  - BACKGROUND: Studies of injection drug use cessation have largely sampled adults
      in drug treatment settings. Little is known about injection cessation and relapse
      among young injection drug users (IDU) in the community. METHODS: A total of 365
      HCV-negative IDU under age 30 years were recruited by street outreach and
      interviewed quarterly for a prospective cohort between January 2000 and February
      2008. Participants were followed for a total of 638 person-years and 1996 visits.
      We used survival analysis techniques to identify correlates of injection
      cessation (> or =3 months) and relapse to injection. RESULTS: 67% of subjects
      were male, median age was 22 years (interquartile range (IQR) 20-26) and median
      years injecting was 3.6 (IQR 1.3-6.5). 28.8% ceased injecting during the follow
      up period. Among those that ceased injecting, nearly one-half resumed drug
      injection on subsequent visits, one-quarter maintained injecting cessation, and
      one-quarter were lost to follow-up. Participating in a drug treatment program in
      the last 3 months and injecting less than 30 times per month were associated with
      injection cessation. Injecting heroin or heroin mixed with other drugs, injecting
      the residue from previously used drug preparation equipment, drinking alcohol,
      and using benzodiazepines were negatively associated with cessation. Younger age
      was associated with relapse to injection. CONCLUSION: These results suggest that
      factors associated with stopping injecting involve multiple areas of
      intervention, including access to drug treatment and behavioral approaches to
      reduce injection and sustain cessation. The higher incidence of relapse in the
      younger subjects in this cohort underscores the need for earlier detection and
      treatment programs targeted to adolescents and transition-age youth.

PMID- 19181457
TI  - The adoption of wraparound services among substance abuse treatment organizations
      serving criminal offenders: The role of a women-specific program.
AB  - Women's substance abuse treatment outcomes are improved when women-specific needs
      are addressed through wraparound services, such as the provision of child care,
      employment assistance, or mental health counseling. Despite a higher prevalence
      of pre-incarceration drug use, women in prison report receiving fewer services
      than their male counterparts, suggesting they likely have greater service needs
      upon release. It is unknown whether community-based treatment organizations with
      a women-specific program offer more wraparound services than programs without a
      focus on women. This study uses data from the Criminal Justice Drug Abuse
      Treatment Studies (CJ-DATS) research cooperative's National Criminal Justice
      Treatment Practices Survey (NCJTPS), a nationally representative sample of
      community-based treatment programs serving predominantly criminal offenders
      (n=217). First, bivariate analyses identified differences between organizations
      with and without a women-specific program on the number of wraparound services
      adopted as well as organizational-level characteristics (i.e., organizational
      structure, personnel characteristics, culture, sources of information, and
      systems integration) related to their adoption. Second, Poisson regression was
      used to identify the organizational characteristics associated with the number of
      adopted wraparound services, with having a women-specific program being the
      primary covariate of interest. Results indicate larger organizations that
      utilized a greater number of treatment approaches and believed that treatment
      could reduce crime were more likely to offer a greater assortment of wraparound
      services. In an effort to improve behavioral treatment outcomes, it is imperative
      to examine organizational-level contextual factors that shape the availability of
      wraparound services for female offenders in community-based substance abuse
      treatment settings.

PMID- 19181459
TI  - Molecular epidemiology of foot-and-mouth disease viruses from South East Asia
      1998-2006: the Lao perspective.
AB  - Foot-and-mouth disease (FMD) causes sporadic disease outbreaks in the Lao
      People's Democratic Republic (Lao PDR) and appears to be endemic within a
      livestock population largely susceptible to infection. As Lao PDR is a major
      thoroughfare for transboundary animal movement, regular FMD outbreaks occur
      causing economic hardship for farmers and their families. The dominant serotype
      causing outbreaks between 1998 and 2006 was type O. Using phylogenetic analysis,
      type O isolated viruses were divided into two topotypes: South East Asia (SEA)
      and the Middle East-South Asia (ME-SA). Type A virus was reported only in 2003
      and 2006 and type Asia 1 only in 1996 and 1998.

PMID- 19181460
TI  - Sequence and classification of FdPV2, a papillomavirus isolated from feline
      Bowenoid in situ carcinomas.
AB  - Bowenoid in situ squamous cell carcinoma (BISC) is a rare feline skin disorder,
      which has been described as often associated with papillomavirus infection. It is
      clinically characterized by solitary or multiple hyperkeratotic plaques affecting
      older cats. Papillomavirus (PV) sequences amplified from feline viral plaques,
      and BISC lesions seldom correspond to FdPV1. The goal of the present study was to
      investigate three cases of BISC and to carry out initial genomic analysis of the
      associated viral DNA. Samples of skin biopsies taken from three BISC cats were
      histologically characterized. DNA was extracted and rolling-circle amplification
      was performed on the skin samples. Restriction enzyme analysis of the amplified
      DNA revealed the presence of a putative unknown PV. The whole genome was
      subsequently sequenced and cloned. Alignments with previously described feline PV
      sequences were carried out and phylogenetic trees were generated. The circular
      7,899 base pair sequence of Felis domesticus PV type 2 (FdPV2) contains a typical
      noncoding region and characteristic open reading frames (ORF) for six putative
      viral proteins. Phylogenetic analysis based on the nucleotide alignment of L1
      genes or the amino acid alignment of E1 proteins of FdPV2 and 52 other PV types
      indicates that FdPV2 might represent a new genus.

PMID- 19181461
TI  - Population dynamics of swine influenza virus in farrow-to-finish and specialised
      finishing herds in the Netherlands.
AB  - Influenza virus infections with subtypes H1N1, H3N2 and H1N2 are very common in
      domestic pigs in Europe. Data on possible differences of population dynamics in
      finishing pigs in farrow-to-finish herds and in specialised finishing herds are,
      however, scarce. The presence of sows and weaned piglets on the same premises
      may, however, affect the exposure of finishing pigs to influenza viruses. In a
      longitudinal study on 14 farrow-to-finish herds and 15 finishing herds, groups of
      pigs were followed by repeatedly testing the same animals for antibodies against
      all three influenza virus subtypes (H1N1, H3N2 and H1N2). At the end of the
      finishing period, the seroprevalences in farrow-to-finish and specialised
      finishing herds were 44.3% and 62.0%, respectively for H1N1, 6.6% and 19.3%,
      respectively for H3N2, and 57.2% and 25.6%, respectively for H1N2. For all three
      subtypes, the incidence of influenza virus infections was highest at the
      beginning of the finishing period in farrow-to-finish herds, while the incidence
      of influenza virus infections was highest at the end of the finishing period in
      finishing herds. Respiratory disease, probably related to the influenza
      infections, was observed in five of these herds only, but also occurred at the
      beginning of the finishing period in farrow-to-finish herds and at the end of the
      finishing period in finishing herds. The observed differences of population
      dynamics of influenza virus may affect choice and timing of intervention
      measures.

PMID- 19181462
TI  - Reliability and validity of standardized Chinese version of Urban Infant-Toddler
      Social and Emotional Assessment.
AB  - AIMS: To evaluate the reliability and validity of the Chinese version of Infant
      Toddler Social and Emotional Assessment (CITSEA). STUDY DESIGN: A cross-sectional
      survey through parent self-administered questionnaires in Chinese urban
      communities. Fourteen cities from the Southern, Northern, Eastern, Western and
      Central China were involved. SUBJECTS: A total of 5323 healthy toddlers (2690
      boys and 2633 girls) aged 12 to 36 months from the 14 cities recruited through a
      multi-stage sampling scheme. OUTCOME MEASURES: Self-administered questionnaire
      was employed to collect the social demographic data, and the Chinese translation
      of ITSEA was used to collect data on children's social and emotional behavior.
      RESULTS: The reliability and validity of CITSEA were examined by standard
      psychometric methods. 1) The test-retest reliability of four broad domains ranged
      from 0.78 to 0.89 at the significant level p<0.001; 2) Split-half reliability
      ranged from 0.82 to 0.90 (p<0.001); 3) The alpha coefficient was noticed to range
      from 0.79 to 0.88, which demonstrated good internal consistency. Furthermore, as
      is hypothesized, the score of CITSEA domains was significantly correlated with
      subscale's score of the Child Behavior Checklist 2/3 (CBCL2/3) and dimension's
      score of China Toddler Temperament. Confirmatory factor analysis demonstrated a
      good and reliable match of the model, indicating that CITSEA outlines the social
      and emotional development of Chinese urban children aged 12 to 36 months.
      CONCLUSION: The Chinese version of ITSEA is valid and the psychometric properties
      of this translated version (including its reliability and validity) are at an
      acceptable standard. It can be used as an instrument for assessing social and
      emotional problems, including delays in social-emotional competence for Chinese
      young children.

PMID- 19181463
TI  - Recovery, cryopreservation and fertilization potential of bovine spermatozoa
      obtained from epididymides stored at 5 degrees C by different periods of time.
AB  - The objetive of the present study was to evaluate the effect of the interval
      between animal's death and sperm recovery on the freezability and fertilizing
      ability of spermatozoa from bull epididymides stored for different periods of
      time. Testis from 25 bulls were collected at the abattoir 2h after the slaughter.
      In the laboratory spermatozoa from one epididymis were recovered and analysed for
      motility. The remaining epididymis was stored for 24h (G24), 48h (G48) and 72h
      (G72) at 5 degrees C. At the end of each time period, spermatozoa were
      recuperated and cryopreserved in Tris-egg yolk and glycerol. Pre-freeze and post
      thaw sperm samples were taken to assess total and progressive motility,
      concentration, membrane integrity and acrosome integrity. For evaluation of
      fertilizing ability, in each time period five straws of each bull were thawed,
      pooled and used for in vitro embryo production. The results showed that after 48h
      of storage there was a decline in total motility, which did not change until 72h.
      Progressive motility, plasma membrane and acrosome integrity were not affected by
      any of the storage periods. Conversely, all sperm parameters, except progressive
      motility, were reduced after cryopreservation. Embryo production was less
      (P<0.05) in the treatments than in the reference group. However, there was no
      differences (P>0.05) in blastoycst rate among experimental groups. Considering
      all the embryos produced by epididymal spermatozoa a greater proportion of female
      embryos was observed, which was similar to the reference embryos. The shift
      observed on sex ratio toward female for those two groups was also observed when
      they were compared with the expected 1:1 ratio (P<0.05). The results showed the
      possibility to produced in vitro embryos using cryopreseved spermatozoa from
      epididymides and stored for long period of time at 5 degrees C. These procedures
      became an important tool for animal preservation when the sperm cells cannot be
      cryopreserved immediately after the animal's death.

PMID- 19181464
TI  - Pig melatonin receptor 1a (MTNR1A) genotype is associated with seasonal variation
      of sow litter size.
AB  - The duration of nocturnal melatonin secretion reaches its minimum in summer, a
      physiological event that is likely related with the diminished sow fertility and
      delayed puberty typically observed in this season. Melatonin exerts its function
      by binding two different receptors named as MTNR1A and MTNR1B. Interestingly, the
      MTNR1A gene is located on a chromosome SSC17 region where QTL for prolificacy
      traits have been detected in previous studies. In this work, we have found a
      synonymous T162C polymorphism at exon 2 of the pig MTNR1A gene. An association
      analysis between this polymorphism and sow prolificacy in an Iberianx Meishan
      intercross was performed. The utilization of four statistical models of
      increasing complexity demonstrated that the MTNR1A gene has both additive and
      dominant effects on total number of born piglets (TNB) and number of piglets born
      alive (NBA). Additive effects were significant in summer (TNB, P<0.01; NBA,
      P<0.001), whereas dominant effects reached significance both in fall (TNB,
      P<0.01; NBA, P<0.05) and in winter (TNB, P<0.001; NBA, P<0.05). The seasonal
      variation observed for MTNR1A additive and dominant effects might be produced by
      the influence of photoperiod on the pattern and duration of melatonin secretion.
      These results illustrate that the complex interaction between genotype and
      environment can be an important source of phenotypic variation of reproductive
      traits.

PMID- 19181465
TI  - Shaping home care in Europe: the contribution of the Aged in Home Care project.
AB  - OBJECTIVES: During the 1990s, use of home care sector has increased substantially
      in Europe. However, research on home care continues to be underreported. This
      article summarizes the findings from the "Aged in Home Care" (ADHOC) study -
      carried out from 2001 to 2004 in Europe - and women's situation in European Home
      Care. METHODS: The review is based on 4 book chapters as well as on 23 articles
      listed in PubMed and published from August 2004 to October 2008. ADHOC used a
      standardized data set collected with the Resident Assessment Instrument for Home
      Care (RAI-HC 2.0); this instrument was used to assess 4010 home care clients at
      11 European sites. The included articles analyzed the sociodemographic and
      clinical characteristics, basic physical needs, provision of selected preventive
      measures, and medication data from the ADHOC sample. In addition home service
      provision, quality indicators, and selected outcomes of home care intervention
      during the course of 1 year were assessed. RESULTS: The mean subject age was 82.3
      years; women were on average 2 years older than men and more frequently lived
      alone, 74% were women. Women suffered more frequently from pain, depression, and
      extreme obesity. There were marked regional differences in both the functional
      status of the clients and the characteristics and use of home care services.
      CONCLUSIONS: The implementation of a common assessment instrument for HC clients
      may help contribute the necessary wealth of data for (re)shaping home care in
      Europe. Policy makers and service providers may learn about best practices in the
      European context.

PMID- 19181466
TI  - Exercise improves cardiovascular control in a model of dislipidemia and
      menopause.
AB  - The present study investigated the effects of exercise training on arterial
      pressure, baroreflex sensitivity, cardiovascular autonomic control and metabolic
      parameters on female LDL-receptor knockout ovariectomized mice. Mice were divided
      into two groups: sedentary and trained. Trained group was submitted to an
      exercise training protocol. Blood cholesterol was measured. Arterial pressure
      (AP) signals were directly recorded in conscious mice. Baroreflex sensitivity was
      evaluated by tachycardic and bradycardic responses to AP changes. Cardiovascular
      autonomic modulation was measured in frequency (FFT) and time domains. Maximal
      exercise capacity was increased in trained as compared to sedentary group. Blood
      cholesterol was diminished in trained mice (191+/-8mg/dL) when compared to
      sedentary mice (250+/-9mg/dL, p<0.05). Mean AP and HR were reduced in trained
      group (101+/-3mmHg and 535+/-14bpm, p<0.05) when compared with sedentary group
      (125+/-3mmHg and 600+/-12bpm). Exercise training induced improvement in
      bradycardic reflex response in trained animals (-4.24+/-0.62bpm/mmHg) in relation
      to sedentary animals (-1.49+/-0.15bpm/mmHg, p<0.01); tachycardic reflex responses
      were similar between studied groups. Exercise training increased the variance
      (34+/-8 vs. 6.6+/-1.5ms(2) in sedentary, p<0.005) and the high-frequency band
      (HF) of the pulse interval (IP) (53+/-7% vs. 26+/-6% in sedentary, p<0.01). It is
      tempting to speculate that results of this experimental study might represent a
      rationale for this non-pharmacological intervention in the management of
      cardiovascular risk factors in dyslipidemic post-menopause women.

PMID- 19181467
TI  - Age-specific prevalence of, and factors associated with, different types of
      urinary incontinence in community-dwelling Australian women assessed with a
      validated questionnaire.
AB  - OBJECTIVE: The aim of this study was to document the age-specific prevalence of
      different types of urinary incontinence (UI) in women and to identify the risk
      factors associated with each type of UI. DESIGN: A detailed self-administered
      questionnaire was mailed to 542 community-dwelling women, aged 24-80 years. The
      questionnaire included a validated instrument, the Questionnaire for Urinary
      Incontinence Diagnosis (QUID), for the assessment of stress, urge and mixed UI.
      RESULTS: Five hundred and six of the 542 women provided data (93.4%). The overall
      prevalence of any UI was 41.7% [95% confidence interval (CI): 37.2-45.8%]. Of the
      210 women reporting UI, 16% [95% CI: 12.9-19.3%] reported stress only; 7.5% [95%
      CI: 5.2-9.8%] reported urge only and 18% [95% CI: 14.7-21.5%] reported a mixed
      pattern. Stress incontinence was most common amongst middle-aged women (25.3% of
      women aged 35-44 years), while urge incontinence was most common in women over
      the age of 75 years (24.2%). In logistic regression analyses, obesity (p<0.001)
      and being parous (p=0.019) were found to be significantly associated with stress
      incontinence, increasing age (p=0.002) with urge incontinence, and being
      overweight (p=0.035) or obese (p<0.001) and having had a hysterectomy (p=0.021)
      with mixed incontinence. CONCLUSIONS: UI is a highly prevalent condition in women
      living in the community. Stress, urge and mixed incontinence have different age
      distributions and risk factors. These data are important in understanding the
      etiology, management and possible prevention of these conditions.

PMID- 19181468
TI  - Integrated contrast-enhanced diagnostic whole-body PET/CT as a first-line
      restaging modality in patients with suspected metastatic recurrence of breast
      cancer.
AB  - OBJECTIVE(S): Only few information exist about the diagnostic accuracy of PET/CT
      for restaging patients with metastatic recurrence of breast carcinoma. Therefore,
      our study hypothesis was to perform diagnostic contrast enhanced CT (ce-CT) and
      FDG-PET in a one-step investigation, to prove sensitivity of each modality and to
      determine whether diagnostic PET/CT adds information over PET or contrast
      enhanced CT alone for restaging of patients with suspected recurrence of breast
      cancer. METHODS: Fifty-two patients with suspected recurrence of breast cancer
      were included in our study. All of them were free of metastasis after the first
      line therapy. Indications for restaging were: Elevated tumor markers n=32,
      clinical deterioration n=16 and/or suspicious findings on other imaging studies
      n=48. Integrated PET/CT was performed using contrast-enhanced diagnostic CT for
      attenuation correction. RESULTS: PET was correct in 44/52 patients (85%), ce-CT
      in 38/52 patients (73%) and PET/CT in 50/52 patients (96%). Sensitivity and
      specificity of lesion detection of PET, CT and PET/CT were 84%, 66% and 93%, and
      100%, 92%, and 100%, respectively. DISCUSSION: PET/CT can improve staging and
      alter therapeutic options in patients suspected to have breast cancer recurrence
      and distant metastatic disease, primarily by demonstrating local or distant nodal
      involvement occult at other imaging studies. The added value of FDG-PET/CT over
      other diagnostic modalities is mainly expressed by the fact that a noninvasive
      whole-body evaluation is possible in a single examination.

PMID- 19181469
TI  - Diffusion-weighted imaging for the follow-up of patients after matrix-associated
      autologous chondrocyte transplantation.
AB  - OBJECTIVE: To evaluate the use of diffusion-weighted imaging (DWI) for the
      assessment of cartilage maturation in patients after matrix-associated autologous
      chondrocyte transplantation (MACT). MATERIALS AND METHODS: Fifteen patients after
      MACT were examined by 3.0-T magnetic-resonance-tomography; the examination was up
      to 13 month after surgery in group 1, and later than 13 month after surgery in
      group 2. Both groups had a follow-up one-year later. DWI was acquired using a
      steady-state gradient-echo sequence. Mean values of the diffusion quotients of
      regions of interest within cartilage repair tissue and of reference regions were
      assessed. Each region-of-interest was subdivided into a deep, and a superficial
      area. RESULTS: Mean diffusion quotients of cartilage repair tissues were 1.44
      (baseline), and 1.44 (follow-up). Mean diffusion quotients of reference tissues
      were 1.29 (baseline) and 1.28 (follow-up). At the follow-up diffusion quotients
      of cartilage repair tissue were significantly higher than those of reference
      cartilage. In group 1 the diffusion quotients were significantly lower at the
      follow-up (1.45 versus 1.65); in group 2 no statistically significant differences
      between follow-up (1.39) and baseline (1.41) were found. Reference cartilages and
      cartilage repair tissues of group 2 showed a decrease of diffusion quotients from
      the deep to the superficial area being stable at the follow-up. In group 1
      initially a significant increase (1.49 versus 1.78) of the diffusion quotients
      from deep to superficial area of the cartilage repair tissue was found changing
      into a decrease (1.65 versus 1.52) at the follow-up. CONCLUSIONS: DWI detected
      changes of diffusion within cartilage repair tissue that may reflect cartilage
      maturation. Changes in diffusity occurred up to two years after surgery and were
      stable later. Zonal variations within cartilage could be measured.

PMID- 19181470
TI  - Renal cell carcinoma in patients with a solitary kidney after nephrectomy treated
      with radiofrequency ablation: mid term results.
AB  - This retrospective study aimed to evaluate the feasibility and effectiveness of
      radiofrequency ablation (RFA) in patients with solitary kidney for the treatment
      of renal cell carcinoma (RCC). Within 2 years 10 patients (seven males, three
      females; age 65+/-8 years) were treated. All patients had a history of
      nephrectomy of the contralateral kidney. The indications for RFA were
      inoperability or high probability of complete renal failure after surgical
      enucleation of the tumor. 13 tumors with a size between 1.9 and 4.2 cm (average
      2.7 cm) were treated. In patients with a tumor diameter larger than 2.5 cm a
      transarterial embolization was performed prior to RFA to reduce heat sink effect
      and risk of bleeding. Therapeutical success was defined as a lack of contrast
      enhancement in follow up examinations and shrinking of the treated area.
      Furthermore all patients' renal function was monitored. RFA of renal tumors under
      CT-fluoroscopy was feasible in all patients. Within the follow up (3 and 24
      months) no tumor recurrence or major complication was detected. One patient
      developed another RCC and was successfully treated with a second RF-ablation.
      None of the patients developed renal failure with the need of hemodialysis. In
      one of the patients a hemorrhage into the surrounding tissue was noticed, which
      stopped spontaneously. RFA is a valuable and effective therapeutical option in
      patients with solitary kidney suffering from inoperable renal cell carcinoma. The
      complication rate is small and an excellent tumor control can be achieved without
      deterioration of the renal function.

PMID- 19181471
TI  - A simple and efficient approach to reversed-phase HPLC method screening.
AB  - The development and utility of an efficient HPLC method screening strategy using
      only four columns for the separation of pharmaceutical compounds and related
      impurities is presented. The strategy established a two-column approach to enable
      rapid early method development, along with a four-column approach for commercial
      method development of the analytical methods utilized to verify the quality of
      drug substance or drug product. Mobile phases consisted of acetonitrile or
      methanol with aqueous trifluoroacetic acid for low pH screening, and ammonium
      hydroxide for high pH screening. Examples are provided to demonstrate the
      practicality and orthogonality of the method screening process. A unique system
      suitability check, using commercially available compounds, was incorporated as a
      tool for troubleshooting and for ensuring adequate system performance prior to
      screening. Initial testing of the strategy revealed that the columns chosen were
      successful in leading to assay and impurity methods for 40 pharmaceutical
      compounds.

PMID- 19181473
TI  - An in-vivo study of the wound-bursting strengths of octyl-cyanoacrylate, butyl
      cyanoacrylate, and surgical tape in rats.
AB  - BACKGROUND: Several non-invasive wound-closure devices are available. Clinical
      studies of low-tension lacerations suggest similar clinical outcomes with these
      devices. OBJECTIVE: We compared the wound-bursting strengths (WBS) of octyl
      cyanoacrylate (Dermabond), butyl-cyanoacrylate (Histoacryl Blue), and adhesive
      tape (Steri-Strips). METHODS: Design-randomized, controlled, blinded experiment.
      Setting-university-based division of laboratory animal research. Subjects-15
      Sprague-Dawley rats weighing 250-350 g. Interventions-standardized 2-cm full
      thickness incisions were made in duplicate on both sides of the rat's dorsum with
      a #15 surgical blade and closed with one of the three study wound-closure devices
      following manufacturer instructions. The order of closure was randomized.
      Measurements-WBS was measured after wound closure with a validated vacuum
      controlled wound chamber device (BT-2000) that measures the pressure required to
      disrupt the closed wound. Data analysis-between-group comparisons were performed
      with pair-wise t-tests and chi-squared tests. This study had 80% power to detect
      a 75-mm Hg between-group difference in WBS (two-tailed alpha = 0.05). RESULTS: We
      evaluated 30 incisions in 15 rats. The mean WBS of octyl-cyanoacrylate (298 +/-
      58 mm Hg) was significantly higher than that of butyl-cyanoacrylate (199 +/- 87
      mm Hg; difference 98 mm Hg [95% confidence interval (CI) 32-165], p = 0.006) or
      Steri-Strips (129 +/- 67 mm Hg; difference 169 mm Hg [95% CI 112-227], p <
      0.001). The WBS of butyl-cyanoacrylate was stronger than that of Steri-Strips;
      difference 71 mm Hg (95% CI 4-138), p = 0.035. CONCLUSIONS: Octyl-cyanoacrylate
      tissue adhesive has a higher WBS than butyl-cyanoacrylate, whose WBS is greater
      than that of surgical tape.

PMID- 19181472
TI  - Evaluation of immunoassays for the measurement of insulin and C-peptide as
      indirect biomarkers of insulin misuse in sport: values in selected population of
      athletes.
AB  - Insulin and C-peptide have been proposed as possible biomarkers of human insulin
      hormone misuse in sport. An extended intra- and inter-laboratory validation of
      commercially available immunoassays was performed. Enzyme Amplified Sensitivity
      Immunoassay (EASIA) assays (Human Insulin-EASIA and C-peptide EASIA kits from
      BioSource) were evaluated for insulin and C-peptide in serum. The intra- and
      inter-laboratory precision and accuracy values were good for the evaluated assays
      with maximum imprecision and inaccuracy of 16% and 23%, respectively, obtained
      just for one day C-peptide assay evaluation. The range of concentrations found in
      serum samples under investigation was always covered by the calibration curves of
      the studied immunoassays. However, a 19.7% of the samples felt below the
      estimated insulin limit of quantification. High concordance between laboratory
      results was obtained for insulin assay (intraclass correlation coefficient 
      ICC=0.857), whereas that for C-peptide was lower (ICC=0.539). Evaluated
      immunoassays were used to measure serum concentrations of insulin and C-peptide
      in elite athletes of various sport disciplines at different moment of training
      season, in recreational athletes at baseline conditions and finally in sedentary
      individuals. Serum insulin was statistically lower both in recreational and elite
      athletes when compared to sedentary individuals. Among elite athletes, the
      specific sport affected serum insulin (e.g., weightlifting) and C-peptide (e.g.,
      triathlon) concentrations. Over the training season, a within athletes
      variability was observed for taekwondo, swimming and weightlifting athletes.
      Variations due to those aspects should be taken in careful consideration in the
      hypothesis of setting reference concentration ranges for doping detection.

PMID- 19181474
TI  - Blunt splenic injuries in the adolescent trauma population: the role of
      angiography and embolization.
AB  - BACKGROUND: Splenic artery embolization (SAE) improves non-operative splenic
      salvage rates in adults, but its utility and safety in the pediatric population
      is less well defined. OBJECTIVE: Because adolescent trauma patients are often
      triaged to adult trauma centers, we were interested in evaluating SAE in this
      particular population. We hypothesize that angiography and embolization is a safe
      and effective adjunct to non-operative management in the adolescent population.
      METHODS: A retrospective review of all patients aged 13-17 years admitted to our
      Level I Trauma Center with blunt splenic injury from 1997-2005 was performed. We
      reviewed patient demographics, operative reports, admission, and follow-up
      abdominal computed tomography (ACT) results, angiographic reports, and patient
      outcomes. RESULTS: A total of 97 patients were reviewed. Eighteen patients
      underwent immediate surgery, and 79 of the remaining patients had planned non
      operative management. Of those participating in non-operative management, 35/79
      (44%) were initially observed and 44/79 (56%) underwent initial angiography,
      23/44 having embolization. Patients in the embolization group had an overall high
      grade of injury (American Association for the Surgery of Trauma mean grade 3.3,
      SD 0.6). The overall splenic salvage rate was 96% (76/79) in the non-operative
      management group; 100% splenic salvage was seen in the observational group; 100%
      salvage was also seen in patients with negative angiography, and 87% salvage
      (20/23) in the splenic artery embolization group. CONCLUSION: Splenic artery
      embolization may be a valuable adjunct in adolescent blunt splenic injury,
      especially in higher grade injuries or with evidence of splenic vascular injury
      on ACT.

PMID- 19181475
TI  - Chest pain, ST elevation, and positive cardiac enzymes in an austere environment:
      differentiating smallpox vaccination-mediated myocarditis and acute coronary
      syndrome in Operation Iraqi Freedom.
AB  - BACKGROUND: Myocarditis is a recognized but rare complication of smallpox
      immunization. It typically presents within 30 days of immunization and on initial
      presentation shares many characteristics with acute coronary syndrome.
      Electrocardiogram findings, elevated cardiac enzymes, and undifferentiated chest
      pain require immediate implementation of therapy directed towards an acute
      coronary syndrome. In an austere environment, access to advanced care may be
      limited. OBJECTIVES: Smallpox vaccine-mediated myocarditis may present, typically
      within 30 days of immunization, in such a fashion that it is impossible to
      distinguish from acute myocardial infarction. The purpose of this article is to
      alert the clinician to this problem and to provide information to assist in
      making a suitable diagnosis and disposition in the absence of an absolute
      diagnosis. CASE REPORT: We present a case of smallpox vaccine-associated
      myocarditis in an American serviceman deployed in Iraq, and review the literature
      to determine management of these cases in an emergency setting. CONCLUSIONS: This
      case serves to increase awareness of the association of vaccine-mediated
      myocarditis in the month after immunization, and the fact that it may present
      similar to infarction. If the clinical probability of myocarditis is greater than
      infarction, this will lead the clinician to different treatment modalities.

PMID- 19181476
TI  - Self-monitoring predicts change in fiber intake and weight loss in adults with
      diabetes following an intervention regarding the glycemic index.
AB  - OBJECTIVE: Self-monitoring can facilitate behavioral change by providing feedback
      regarding goal attainment. Glycemic index (GI) quantifies the glycemic response
      to carbohydrate-containing foods. Low GI diets may improve weight and glycemic
      control. We examined the relation between self-monitoring and changes in diet and
      body weight following an intervention in which consumption of low GI foods was
      encouraged among adults aged 40-70 years with diabetes. METHODS: Pre/post
      intervention dietary intake was assessed with 24-h dietary recalls and weight was
      obtained. Mean number of days participants kept self-monitoring records was
      determined. The impact of self-monitoring on the change in GI, fiber intake,
      weight and body mass index (BMI) was evaluated using regression analyses.
      RESULTS: Each additional day of self-monitoring was associated with a mean
      reduction in weight and BMI of -0.95 kg and -0.34 kg/m(2), respectively. The mean
      change in fiber intake increased in men but did not significantly change in women
      for each additional day of monitoring. CONCLUSION: Self-monitoring was associated
      with weight loss in men and women and greater fiber intake in men. PRACTICE
      IMPLICATIONS: Men can self-monitor to lose weight and increase fiber intake. Self
      monitoring facilitates weight loss in women but other behavioral strategies are
      needed to improve fiber intake.

PMID- 19181477
TI  - In vitro chemosensitivity based on depth of invasion in advanced colorectal
      cancer using ATP-based chemotherapy response assay (ATP-CRA).
AB  - BACKGROUND: Tumors are composed of subpopulations of cells with heterogeneous
      characteristics that allow for tumor progression and development of treatment
      resistance. The purpose of this study was to determine if there is heterogeneity
      in the in vitro chemosensitivity in different invasive sections of a single
      tumor. MATERIALS AND METHODS: Chemosensitivity in advanced colorectal cancer
      specimens was examined using an ATP-based chemotherapy response assay. Four
      chemotherapeutic agents (5-fluorouracil (5-FU), oxaliplatin, irinotecan, and
      mitomycin) were used for chemosensitivity studies. Tumor tissues were obtained
      from the superficial (mucosa/submucosa) and deep parts (muscle/subserosa/serosa),
      respectively. Twenty patients who had results for both the superficial and deep
      parts were evaluated. RESULTS: The chemosensitivity study showed variable cell
      death rates in both parts of the tumor. Regression analysis showed some
      correlations with 5-FU and irinotecan, but not with oxaliplatin or mitomycin.
      With the exception of three patients in whom no drug was recommended, at least
      one chemotherapeutic drug showed some consistency between the superficial and
      deep parts of the tumor. Mitomycin was the most frequently active agent for the
      superficial part. In the deep part, oxaliplatin and mitomycin were the most
      active agents. CONCLUSIONS: There may be heterogeneity in the responses to anti
      chemotherapeutic agents in advanced colorectal cancer, according to the depth of
      invasion. Therefore, in clinical situations, chemosensitivity test specimens
      should be mixed with various parts of the whole tumor in order to obtain
      representative chemosensitivity and chemoresistance profiles.

PMID- 19181478
TI  - [Can we prevent the chronic post-surgical pain? Pain and Locoregional Anesthesia
      Committee and the Standards Committee of the French Society of Anesthesia and
      Intensive Care].

PMID- 19181479
TI  - [Prevention of aspiration of gastric contents (Mendelson syndrome) in obstetrics:
      should tracheal intubation remain an inviolable principle?].

PMID- 19181480
TI  - Reliability and responsiveness of the Bruininks-Oseretsky Test of Motor
      Proficiency-Second Edition in children with intellectual disability.
AB  - We examined the internal consistency, test-retest reliability, and the
      responsiveness of the Bruininks-Oseretsky Test of Motor Proficiency-Second
      Edition (BOT-2) for children with intellectual disabilities (ID). One hundred
      children with ID aged 4-12 years tested on 3 separate occasions: two baseline
      measurements with a 2-week interval before the intervention, and a follow-up
      measurement after 4 months of pediatric rehabilitation program. The test-retest
      reliability and internal consistency of the total scale were excellent, with an
      ICC of 0.99 (95% confidence interval) and alpha of 0.92. Responsiveness was
      acceptable for all BOT-2 measures except the balance subtest. The minimal
      detectable change (MDC) and the minimal important difference (MID) values yielded
      a lower sensitivity level but a higher specificity level. Implications for
      interpreting these responsiveness indices are discussed.

PMID- 19181481
TI  - Treatment of bruxism in individuals with developmental disabilities: a systematic
      review.
AB  - We reviewed studies involving the treatment of bruxism (i.e., teeth clenching or
      teeth grinding) in individuals with developmental disabilities. Systematic
      searches of electronic databases, journals, and reference lists identified 11
      studies meeting the inclusion criteria. These studies were evaluated in terms of:
      (a) participants, (b) procedures used to assess bruxism, (c) intervention
      procedures, (d) results of the intervention, and (e) certainty of evidence.
      Across the 11 studies, intervention was provided to a total of 19 participants
      aged 4-43 years. Assessment procedures included dental screening under sedation
      and interviews with caregivers. Intervention approaches included prosthodontics,
      dental surgery, injection of botulinum toxin-a, behavior modification, music
      therapy, and contingent massage. Positive outcomes were reported in 82% of the
      reviewed studies. Overall, the evidence base is extremely limited and no
      definitive statements regarding treatment efficacy can be made. However, behavior
      modification and dental or medical treatment options (e.g., prosthodontics) seem
      to be promising treatment approaches. At present, a two-step assessment process,
      consisting of dental screening followed by behavioral assessment, can be
      recommended.

PMID- 19181482
TI  - STREGA, STROBE, STARD, SQUIRE, MOOSE, PRISMA, GNOSIS, TREND, ORION, COREQ,
      QUOROM, REMARK... and CONSORT: for whom does the guideline toll?

PMID- 19181483
TI  - Deficiency of thrombospondin-1 reduces Th17 differentiation and attenuates
      experimental autoimmune encephalomyelitis.
AB  - Transforming growth factor beta (TGF-beta) plays a role both in the induction of
      Treg and in the differentiation of the IL-17-secreting T cells (Th17) which drive
      inflammation in experimental autoimmune encephalomyelitis (EAE). We investigated
      the role that thrombospondin-1 (TSP-1) dependent activation of TGF-beta played in
      the generation of an encephalitic Th17 response in EAE. Upon immunization with
      myelin oligodendrocyte glycoprotein peptide (MOG(35-55)), TSP-1 deficient (TSP
      1(null)) mice and MOG(35-55) TCR transgenic mice that lack of TSP-1 (2D2 x TSP
      1(null)) exhibited an attenuated form of EAE, and secreted lower levels of IL-17.
      Adoptive transfer of in vitro-activated 2D2 x TSP-1(null) T cells induced a
      milder form of EAE, independent of TSP-1 expression in the recipient mice.
      Furthermore, in vitro studies demonstrated that anti-CD3/anti-CD28 pre-activated
      CD4+ T cells transiently upregulated latent TGF-beta in a TSP-1 dependent way,
      and such activation of latent TGF-beta was required for the differentiation of
      Th17 cells. These results demonstrate that TSP-1 participates in the
      differentiation of Th17 cells through its ability to activate latent TGF-beta,
      and enhances the inflammatory response in EAE.

PMID- 19181485
TI  - Psychopathology and cognition in divergent functional outcomes in schizophrenia.
AB  - Cognitive performance rather than symptoms, especially positive symptoms, is
      regarded as the primary predictor of functional outcome in schizophrenia.
      However, contradictory evidence exists and many studies fail to sample from the
      extremes of outcome measures. This study tested whether the differential
      importance assigned to symptoms and cognitive impairment is supportable in
      patients with high and low levels of community independence. Schizophrenia
      patients with highly unfavorable (n=24) and highly favorable (n=28) functional
      outcomes as defined by community support requirements were studied. Standard
      cognitive and psychopathology measures were analyzed using independent groups
      comparisons and outcome prediction with logistic regression methods. Symptom
      severity and cognitive data separately accounted for significant amounts of
      variance in community independence. Positive as well as negative symptoms, non
      psychotic psychopathology and cognition generated large effect sizes between
      highly unfavorable and favorable outcome groups. The conditional validity of both
      overall psychopathology and positive symptoms was significant over and above the
      contribution of cognition to outcome prediction. Results suggest researchers may
      have underestimated the role of psychopathology in general and positive symptoms
      in particular as potential determinants of functional status in schizophrenia.

PMID- 19181486
TI  - Serenoa repens associated with Urtica dioica (ProstaMEV) and curcumin and
      quercitin (FlogMEV) extracts are able to improve the efficacy of prulifloxacin in
      bacterial prostatitis patients: results from a prospective randomised study.
AB  - We report the results of a prospective randomised study to evaluate the
      therapeutic effect of Serenoa repens, Urtica dioica (ProstaMEV), quercitin and
      curcumin (FlogMEV) extracts associated with prulifloxacin in patients affected by
      chronic bacterial prostatitis (CBP). From a whole population of 284 patients, 143
      patients affected by CBP [National Institutes of Health (NIH) class II
      prostatitis] were enrolled. All patients received prulifloxacin 600 mg daily for
      14 days, in accordance with antibiogram results. Patients were split into two
      groups: Group A received prulifloxacin associated with ProstaMEV and FlogMEV;
      Group B received only antibiotic therapy. Microbiological and clinical efficacies
      were tested by two follow-up visits at 1 month and 6 months, respectively.
      Quality of life (QoL) was measured using the NIH Chronic Prostatitis Symptom
      Index (CPSI) and International Prostatic Symptom Score (IPSS) questionnaires.
      Group A comprised 106 patients and Group B comprised 37 patients. One month after
      treatment, 89.6% of patients who had received prulifloxacin associated with
      ProstaMEV and FlogMEV did not report any symptoms related to CBP, whilst only 27%
      of patients who received antibiotic therapy alone were recurrence-free (P <
      0.0001). Significant differences were found between groups in terms of symptoms
      and QoL (P < 0.0001 for both). Six months after treatment, no patients in Group A
      had recurrence of disease whilst two patients in Group B did. Questionnaire
      results demonstrated statistically significant differences between groups (all P
      < 0.001). The association of S. repens, U. dioica (ProstaMEV), quercitin and
      curcumin (FlogMEV) extracts is able to improve the clinical efficacy of
      prulifloxacin in patients affected by CBP.

PMID- 19181484
TI  - Association of the 5'-upstream regulatory region of the alpha7 nicotinic
      acetylcholine receptor subunit gene (CHRNA7) with schizophrenia.
AB  - BACKGROUND: The alpha7 neuronal nicotinic acetylcholine receptor subunit gene
      (CHRNA7) is localized in a chromosomal region (15q14) linked to schizophrenia in
      multiple independent studies. CHRNA7 was selected as the best candidate gene in
      the region for a well-documented endophenotype of schizophrenia, the P50 sensory
      processing deficit, by genetic linkage and biochemical studies. METHODS: Subjects
      included Caucasian-Non Hispanic and African-American case-control subjects
      collected in Denver, and schizophrenic subjects from families in the NIMH
      Genetics Initiative on Schizophrenia. Thirty-five single nucleotide polymorphisms
      (SNPs) in the 5'-upstream regulatory region of CHRNA7 were genotyped for
      association with schizophrenia, and for smoking in schizophrenia. RESULTS: The
      rs3087454 SNP, located at position -1831 bp in the upstream regulatory region of
      CHRNA7, was significantly associated with schizophrenia in the case-control
      samples after multiple-testing correction (P=0.0009, African American; P=0.013,
      Caucasian-Non Hispanic); the association was supported in family members. There
      was nominal association of this SNP with smoking in schizophrenia. CONCLUSIONS:
      The data support association of regulatory region polymorphisms in the CHRNA7
      gene with schizophrenia.

PMID- 19181487
TI  - Dopamine and serotonin release in the nucleus accumbens during starvation-induced
      hyperactivity.
AB  - Activity-based anorexia (ABA) is considered an animal model for anorexia nervosa
      (AN). By scheduled feeding and voluntary wheel running, it mimics severe body
      weight loss and increased physical activity in AN. Pharmacological, genetic and
      imaging studies implicate dopamine and serotonin in the regulation of feeding
      behavior, food-anticipatory activity, and food reward. Previous studies propose
      that the nucleus accumbens (NAc) plays an important role in these food-related
      processes. Here we determined dopamine and serotonin levels in the NAc upon
      exposure to the ABA model. Surprisingly, the release of dopamine and serotonin in
      the NAc were not increased during the initiation of food-anticipatory behavior in
      ABA rats. Dopamine release in the NAc was increased during feeding behavior in
      ABA rats. During ABA, levels of serotonin were low and circadian activity is
      blunted. We conclude that during the early stages of development of food
      anticipatory activity, increased dopamine does not trigger hyperactivity.

PMID- 19181489
TI  - A solid-state NMR investigation of the structure of mesoporous silica
      nanoparticle supported rhodium catalysts.
AB  - A detailed study of the chemical structure of mesoporous silica catalysts
      containing rhodium ligands and nanoparticles (RhP-MSN) was carried out by multi
      dimensional solid-state NMR techniques. The degree of functionalization of the
      rhodium-phosphinosilyl complex to the surface of the RhP-MSN channels was
      determined by (29)Si NMR experiments. The structural assignments of the rhodium
      phosphinosilyl complex were unambiguously determined by employing the novel,
      indirectly detected heteronuclear correlation ((13)C-(1)H and (31)P-(1)H
      idHETCOR) techniques, which indicated that oxidation of the attached
      phosphinosilyl groups and detachment of Rh was enhanced upon syngas conversion.

PMID- 19181488
TI  - Spatio-temporal expression of tryptophan hydroxylase isoforms in murine and human
      brain: convergent data from Tph2 knockout mice.
AB  - Dysregulation of tryptophan hydroxylase (TPH)-dependent serotonin (5-HT)
      synthesis, has been implicated in various neuropsychiatric disorders, although
      the differential expression pattern of the two isoforms is controversial. Here,
      we report a comprehensive spatio-temporal isoform-specific analysis of TPH1 and
      TPH2 expression during pre- and postnatal development of mouse brain and in adult
      human brain. TPH2 expression was consistently detected in the raphe nuclei, as
      well as in fibers in the deep pineal gland and in small intestine. Although TPH1
      expression was found in these peripheral tissues, no significant TPH1 expression
      was detected in the brain, neither during murine development, nor in mouse and
      human adult brain. In support of TPH2 specificity in brain 5-HT synthesis, raphe
      neurons of Tph2 knockout mice were completely devoid of 5-HT, with no
      compensatory activation of Tph1 expression. In conclusion, our findings indicate
      that brain 5-HT synthesis across the lifespan is exclusively maintained by TPH2.

PMID- 19181490
TI  - Spin-lattice relaxation study of the methyl proton dynamics in solid 9,10
      dimethyltriptycene (DMT).
AB  - Proton spin-lattice relaxation studies are performed for powder samples of 9,10
      dimethyltriptycene (DMT) and its isotopomer DMT-d(12) in which all the non-methyl
      protons in the molecule are replaced by deuterons. The relaxation data are
      interpreted in terms of the conventional relaxation theory based on the random
      jump model in which the Pauli correlations between the relevant spin and
      torsional states are discarded. The Arrhenius activation energies, obtained from
      the relaxation data, 25.3 and 24.8 kJ mol(-1) for DMT and DMT-d(12),
      respectively, are very high as for the methyl groups. The validity of the jump
      model in the present case is considered from the perspective of Haupt theory in
      which the Pauli principle is explicitly invoked. To this purpose, the dynamic
      quantities entering the Haupt model are reinterpreted in the spirit of the damped
      quantum rotation (DQR) approach introduced recently for the purpose of NMR
      lineshape studies of hindered molecular rotators. Theoretical modelling of the
      relevant methyl group dynamics, based on the DQR theory, was performed. From
      these calculations it is inferred that direct assessments of the torsional
      barrier heights, based on the Arrhenius activation energies extracted from
      relaxation data, should be treated with caution.

PMID- 19181491
TI  - Banana peel: a green and economical sorbent for the selective removal of Cr(VI)
      from industrial wastewater.
AB  - This study describes the use of banana peel, a commonly produced fruit waste, for
      the removal of Cr(VI) from industrial wastewater. The parameters pH, contact
      time, initial metal ion concentration, and temperature were investigated and the
      conditions resulting in rapid and efficient adsorption (95% within 10 min) were
      determined. The binding of metal ions was found to be pH dependent with the
      optimal sorption occurring at pH 2. The retained species were eluted with 5 mL of
      2M H(2)SO(4). To elucidate the mechanism of the process, total amounts of
      chromium and Cr(VI) were analyzed using flame atomic absorption and ultraviolet
      visible (UV-vis) spectroscopic techniques, respectively. The Langmuir and Dubinin
      Radushkevich (D-R) isotherms were used to describe the partitioning behavior for
      the system at different temperatures. Kinetics and thermodynamics of Cr(VI)
      removal by banana peel were also studied. The influence of diverse ions on the
      sorption behavior revealed that only Fe(II) ions (of those tested) suppressed the
      sorption of Cr(VI) ions to some extent. The method was applied for the removal of
      Cr(VI) from industrial wastewater.

PMID- 19181492
TI  - Effect of electromagnetic field and surface modification on the electrical
      behavior of novel solid lipid nanoparticles covered with l-arginine.
AB  - Solid lipid nanoparticles (SLNs) were fabricated with modification of bioactive l
      arginine in their exterior region. The lipid cores of these biomimetic SLNs
      contained cacao butter (CB) and tripalmitin varying between 0% and 7%. Effects of
      lipid composition, l-arginine coverage, and electromagnetic field (EMF) on the
      electrical properties of the novel SLNs were investigated. The morphological
      micrographs revealed that the particle size distribution of the spherical SLNs
      was quite uniform. Based on small-angle X-ray scattering of the SLNs, thickness
      of the external layers was about 4.5nm. An increase in the percentage of CB in
      the emulsified fluids increased average diameter and charge of the SLNs in
      general. An increase in the percentage of CB however decreased particle softness.
      In addition, a higher fraction of the surface coverage of l-arginine yielded a
      higher average diameter and softness of the SLNs. On the contrary, an increase in
      the surface coverage of l-arginine on the SLNs decreased charge in the peripheral
      zone. In regard to electromagnetic regulation, the exposure to EMF reduced charge
      and increased softness of the SLNs. From biomedical aspect, these SLNs could be
      potentially applied to drug entrapment and targeted delivery in preclinical
      trials.

PMID- 19181494
TI  - In vitro cyto-biocompatibility and cell detachment of temperature-sensitive
      dextran hydrogel.
AB  - A series of poly(NIPAAm-co-GMA-Dex) hydrogels were synthesized from glycidyl
      methacrylate-derivatized dextran (GMA-Dex) and N-isopropylacrylamide (NIPAAm) in
      aqueous solution. The swelling properties, cell culture and detachment behaviors
      of these hydrogels were investigated. It has found that poly(NIPAAm-co-GMA-Dex)
      hydrogels are not only sensitive to temperature in deionized water and Dulbecco's
      modified eagle medium (DMEM) (10% FBS), but also exhibit good biocompatibility.
      In addition, L929 cells were found to detach from the hydrogel surface naturally
      without affecting the function of L929 by controlling environmental temperature.

PMID- 19181493
TI  - Improved surface stability and biotin binding properties of streptavidin coating
      on polystyrene.
AB  - The ultimate nature of streptavidin to bind biotin tightly is widely utilized in
      many solid-phase based applications to provide a universal binding surface for
      biotinylated molecules. However, the preparation of the streptavidin coatings by
      passive adsorption may heavily alter the binding properties of native
      streptavidin and may not result in the best possible capture surface for
      demanding solid-phase assays. By introducing sulphydryl groups through primary
      amines in the protein, we have activated and conjugated native streptavidin into
      larger protein polymers resulting in high local binding density when coated on
      polystyrene. This thiolated streptavidin formed through chemical modification has
      improved adsorption properties and biotin binding capability, compared to the
      native streptavidin. When this thiolated streptavidin is coated on polystyrene, a
      dense surface is formed, which provides up to 3-fold increase in the biotin
      binding efficiency and improves the surface stability by minimizing the
      desorption of the adsorbed protein from the surface during incubation.
      Furthermore, this high-capacity surface is resistant to harsh chemical
      treatments, such as denaturing conditions or mild reducing conditions. The
      improved adsorption properties of the thiolated streptavidin allow the coating
      process to be performed with shorter incubation times (15min), still providing
      enhanced solid-phase properties, compared to a reference streptavidin surface.

PMID- 19181495
TI  - Preparation and properties of carrageenan microspheres containing allopurinol and
      local anesthetic agents for the treatment of oral mucositis.
AB  - For the treatment of oral mucositis, carrageenan microspheres containing
      allopurinol and local anesthetic agents, such as lidocaine hydrochloride,
      dibucaine hydrochloride and tetracaine hydrochloride were prepared using a spray
      drying method. As base materials, kappa-carrageenan and iota-carrageenan were
      evaluated, since carrageenan mitigates bitter taste of lidocaine hydrochloride,
      dibucaine hydrochloride and tetracaine hydrochloride. The microspheres were
      spherical and their average diameters were about 10 microm. The drug loading
      efficiency was more than 70%. Allopurinol and local anesthetic agents became
      amorphous by the spray drying. Allopurinol and the local anesthetic agents were
      released from the microspheres for at least 400 min when iota-carrageenan was
      used as a base material. On the other hand, the release was prolonged to 600 min
      when kappa-carrageenan was used. The microspheres were spread and made membranes
      at the air/water interfaces immediately after dropped on the water surfaces. The
      properties of the microspheres such as dispersing efficacy and membrane
      production on the water surfaces suggest that the microspheres can uniformly
      cover inner surfaces of oral cavity to prevent and treat oral mucositis.

PMID- 19181496
TI  - [The role of the hospital in the protection of children].

PMID- 19181497
TI  - [Turicella otitidis infection: otitis media complicated by mastoiditis].
AB  - Turicella otitidis is a nonfermentative, Gram-positive bacillus, which is almost
      exclusively isolated from the ear. Few cases of infection caused by T. otitidis
      have been reported in the literature, but the pathogenic potential of this little
      known bacterium remains controversial, particularly in acute and chronic otitis
      media. CLINICAL OBSERVATIONS: A retrospective study of T. otitidis isolated in
      the University Hospital of Montpellier in 2004 found T. otitidis in 13 patients.
      Among them, a 3-year-old girl had presented with acute and perforated otitis
      media and mastoiditis caused by T. otitidis, thereby confirming the pathogenic
      effect of this bacterium. CONCLUSION: T. otitidis is relatively frequently
      isolated from middle ear samples in healthy patients. However, T. otitidis has
      been implicated in serious cases of infection and should be considered an
      opportunistic pathogen. Its clinical significance can be difficult to establish
      and each case should be carefully interpreted. From a bacteriological point of
      view, T. otitidis should be precisely identified to obtain more information
      regarding its role in clinical pathology.

PMID- 19181498
TI  - [Mild cystic fibrosis: genetics - extending follow-up is necessary].
AB  - The diagnosis of mild cystic fibrosis is first suspected on mild lung disease or
      absence of pancreatic insufficiency and is assessed by biological analysis. The
      sweat test is not always conclusive. The nasal potential difference and molecular
      analysis of CFTR gene allow confirming diagnosis. A regular follow-up in cystic
      fibrosis clinical centre is essential all life long. The genotype, especially
      during neonatal period, cannot be used to predict individually the course of the
      disease. Genetic counselling must be recommended to the parents in order to
      propose an analysis of CFTR gene to give the appropriate genetic counselling and
      to consider with them which family members could be concerned, especially in the
      event of parental project. The research of heterozygote status in related for
      prenatal diagnosis is not recommended for all mutations.

PMID- 19181499
TI  - [Neonatal cholestasis in an intermediate phenotype of type 2 Gaucher disease].

PMID- 19181500
TI  - [Impact of influenza rapid diagnostic tests (IRDT) on the diagnosis of influenza
      and on the management of influenza in children in ambulatory pediatric setting].
AB  - OBJECTIVE: Several studies have highlighted the assets of the influenza rapid
      diagnostic tests (IRDT) for the emergency department management of febrile
      children. The objective of this study was to determine in ambulatory pediatric
      setting impact of IRDT on the management of febrile children during an epidemic,
      especially on other diagnostic testing performed, antibiotic and antiviral
      treatments. METHODS: During an influenza epidemic, 37 paediatricians in three
      different areas of France included all children presenting fever with respiratory
      illnesses; they performed IRDT (test QuickVue for Influenza A and B, Quidel).
      Data collected were antiflu vaccination, previous asthma, symptoms, clinical
      signs, other diagnostic testing performed, and a follow-up two weeks later.
      RESULTS: Between December, 2006 and April, 2007, 695 children entered the
      program. The average age of those children was 4.1 years old (SD 3.4), median 3.2
      (0.07-17.5). In 41.6% of the cases, the tests proved positive. Among 13 symptoms
      of influenza, only five were significantly more present in the group IRDT+:
      shiver (68.1% versus 57.4%), asthenia (87% versus 79.9%), cough (87.5% versus
      70.1%), rhinorrhea (93.4% versus 83.3%), and sleepiness (54.2% versus 43.4%). The
      number of laboratory tests and radiographs ordered were less frequent in group
      IRDT+ than in group IRDT-: respectively 0.7% versus 11.6%, and 0.7% versus 8.6%
      (p<0.0001). IRDT+ group received antibiotics in 7.6% of cases (22 patients, 20
      for OMA) and antiviral in 64.7%. IRDT- group received respectively 18.5%
      antibiotics, and no antiviral (p<0.0001). CONCLUSION: This study confirms the
      difficulty of clinical influenza diagnosis, and suggests the assets of IRDT to
      diagnose influenza and to improve the management of influenza in ambulatory
      paediatric setting.

PMID- 19181501
TI  - Gestational diabetes and pregnancy outcome: do we need an update on diagnostic
      criteria?

PMID- 19181502
TI  - The age- and gender-dependent effects of desflurane and sevoflurane on rat liver.
AB  - OBJECTIVE: This study aimed to investigate the age- and gender-dependent effects
      of desflurane and sevoflurane on the liver. MATERIAL AND METHOD: Upon the
      approval of ethics committee, 84 rats were divided into four groups as 21 young
      male, 21 young female, 21 old male, and 21 old female rats. Then, each group was
      further divided into three groups as desflurane, sevoflurane, and control groups.
      Maintaining the minimum alveolar concentration of 1, desflurane at 6vol% and
      sevoflurane at 2vol% in 6Lmin(-1) 100% O2 were administered for 2h in a
      transparent plastic container of 40cmx40cmx70cm. Each liver preparation was
      evaluated for hydropic degeneration, nuclear polymorphism, portal neutrophile
      infiltration, portal lymphocyte infiltration, and focal necrosis, and each
      preparation was assigned injury points of 0-3; thus, the number of
      histopathologically injured cases, total injury scores of each preparation, and
      the mean injury scores of each group were determined. RESULTS: Desflurane and
      sevoflurane did not significantly increase hepatic injury in the young male rats,
      while both agents caused significantly more hepatic injury in the young female
      rats. In the old rats, both desflurane and sevoflurane inflicted more hepatic
      injury on both genders. In addition, desflurane caused more hepatic injury in the
      old female rats than in the young female or the old male rats. CONCLUSION:
      Hepatic injury associated with desflurane and sevoflurane was mild to moderate,
      suggesting that both agents can be safely used in routine anaesthesia procedures.

PMID- 19181503
TI  - Silibinin prevents TPA-induced MMP-9 expression and VEGF secretion by
      inactivation of the Raf/MEK/ERK pathway in MCF-7 human breast cancer cells.
AB  - Matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF)
      expression are pivotal steps in cancer metastasis. Herein, we investigated the
      effect of silibinin, a major constituent (flavanolignan) of the fruits of Silybum
      marianum, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 and VEGF
      expression in MCF-7 human breast cancer cells. The expression of MMP-9 and VEGF
      in response to TPA was increased, whereas TPA-induced MMP-9 and VEGF expression
      was decreased by silibinin. To investigate the regulatory mechanism of silibinin
      on TPA-induced MMP-9 and VEGF expression, we pretreated cells with various
      inhibitors, such as UO126 (MEK1/2 inhibitor), SP600125 (JNK inhibitor), and
      SB203580 (p38 inhibitor). Interestingly, TPA-induced MMP-9 expression was
      significantly inhibited by UO126, but not by SP600125 and SB203580. In addition,
      we pretreated cells with 100 microM silibinin prior to TPA treatment. TPA-induced
      MEK and ERK phosphorylation was significantly decreased by silibinin in MCF7
      cells. TPA-induced VEGF expression was also suppressed by UO126. On the other
      hand, we found that adenoviral constitutive active-MEK (Ad-CA-MEK) significantly
      increased MMP-9 and VEGF expression. Taken together, we suggest that the
      inhibition of TPA-induced MMP-9 and VEGF expression by silibinin is mediated by
      the suppression of the Raf/MEK/ERK pathway in MCF-7 breast cancer cells.

PMID- 19181504
TI  - Bioactivity-guided fractionation for analgesic properties and constituents of
      Vitex negundo L. seeds.
AB  - This study was undertaken to ascertain the analgesic properties of Vitex negundo
      L. seeds and to isolate and characterize the active constituents. Among the 80%
      ethanol extract and some fractions with different polarity, the acetoacetate
      fraction showed the highest anti-nociceptive activity in acetic acid-induced
      writhing test in ICR mice. The analgesic bioguided isolation of the acetoacetate
      fraction yielded two major lignans: 6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3
      hydroxymethyl-7-methoxy-3,4-dihydro-2-naphthaldehyde (1) and vitedoamine A (2).
      Given orally, compound (1), which was more productive, produced significant
      inhibitions on chemical nociception induced by intraperitoneal acetic acid and
      subplantar formalin injections and exhibited notable anti-inflammatory activities
      in dimethyl benzene-induced ear edema test in a dose-dependent manner. Since co
      administration of naloxone fails to antagonize the analgesic activity of compound
      (1) in the formalin test, we suggest that compound (1) possesses potent analgesic
      effects which are most likely to be mediated by its anti-inflammatory activity
      rather than through opioid receptor system and therefore could partially explain
      the anti-nociceptive effect of V. negundo L. seeds.

PMID- 19181505
TI  - The phytoestrogen ferutinin improves sexual behavior in ovariectomized rats.
AB  - The present study was designed to examine the effect of ferutinin chronic
      administration on sexual behavior of ovariectomized non-estrogen-primed rats.
      Starting from 3 weeks after ovariectomy, female rats were orally treated with
      ferutinin at the doses of 0.2 and 0.5 mg/kg, daily for 4 weeks. Ferutinin's
      effect was compared with that of estradiol benzoate, subcutaneously injected at
      the dose of 1.5 microg/rat twice a week. Animals were tested for sexual
      motivation, receptivity and proceptivity after 1, 2 and 3 weeks of treatment and
      for paced mating behavior after 4 weeks of treatment. Before each experimental
      test, they received progesterone injection (500 microg/rat). Both dosages of
      ferutinin significantly increased the receptive behavior in a time-dependent
      manner, as well as estradiol benzoate did. Also proceptive behaviors increased in
      ferutinin-treated animals in comparison with control ones. During the partner
      preference test ferutinin was able to induce a significant preference for a
      sexually active male over a sexually receptive female. Moreover, ferutinin
      restored a normal paced mating behavior, which had been suppressed by
      ovariectomy. These results show that ferutinin exerts an estrogenic activity in
      ovariectomized non-estrogen-primed female rats.

PMID- 19181506
TI  - Estrogen modulates permeability and prostaglandin levels in the rabbit urinary
      bladder.
AB  - The purpose of this study was to characterize barrier function, hypoxic damage
      and prostaglandin levels in the urinary bladder in response to estrogen
      deficiency. Female New Zealand White rabbits were separated into three groups:
      ovariectomized; sham-operated; and ovariectomized treated with estrogen. Barrier
      function was compromised in the ovariectomized group compared to that of the sham
      group and the ovariectomized group treated with estrogen. Urinary bladders of
      ovariectomized animals showed higher concentrations of hypoxic markers than
      controls, localized primarily in the urothelium. Levels of 6-keto-PGF(1alpha) and
      PGF(2alpha) were significantly higher in smooth muscle than the ovariectomized
      animals and PGE(2) levels were significantly lower in the mucosa of
      ovariectomized animals. These results suggest that estrogen deficiency induces a
      loss of barrier function and an increase in hypoxia. The estrogen-dependent
      decreases of prostaglandin PGE(2) in the urothelium correlate with loss of
      barrier function, suggesting estrogen regulation of PGE(2) may contribute to
      maintenance of urothelial function.

PMID- 19181507
TI  - Epidemiological features of Turkish patients with sarcoidosis.
AB  - Epidemiological characteristics of sarcoidosis differ according to geographical
      distribution. The aim of our study was to disclose epidemiological
      characteristics in our country. The data was collected from investigators, who
      sent information on newly-diagnosed patients via internet. In 2 years 198 female
      and 95 male patients were enrolled to the study (f/m:2.08). Mean age of patients
      was 44+/-13 years (17-90). Mean age of male patients was 38+/-12 while mean age
      of female patients was 48+/-13 (p<0.001). 73.4% of patients were nonsmokers
      (85.4% of females; 48.4% of males; (p<0.001)). About 50% of our 293 patients were
      housewives. Familial sarcoidosis was found in 3 patients' first degree relatives.
      Estimated annual incidence of sarcoidosis for Turkey was calculated as 4 per
      100,000 person. According to our study, 2/3 of sarcoidosis patients were women;
      mean age of patients was 45 and the disease began 10 years later in female
      patients. 80% of patients were nonsmokers; negative relation between sarcoidosis
      and smoking was evident especially in women. Familial sarcoidosis frequency was
      lower compared to other studies in the literature. There was no occupational
      exposure history in our patients. Our incidence rate, is similar with the results
      of other European studies.

PMID- 19181508
TI  - High resolution computed tomography and pulmonary function in common variable
      immunodeficiency.
AB  - Patients with common variable immunodeficiency (CVID) have impaired production of
      immunoglobulins and hence recurrent airway infections, which in turn may lead to
      radiological changes and impaired lung function. Uncertainty exists about the
      nature and frequency of the radiological and the physiological abnormalities, and
      how they relate to each other. We reassessed high resolution computed tomography
      (HRCT) images in 65 patients, reported results from previously measured lung
      function tests, and studied relations between radiology, function and clinical
      variables. Airway obstruction, ventilatory restriction and impaired gas diffusion
      was found in 40, 34 and 21% of the patients, respectively. HRCT abnormalities
      were present in 94% of the subjects, mild changes being the most common.
      Bronchial wall thickening, found in two thirds of the patients, was related to
      airway obstruction and impaired gas diffusion. Linear and/or irregular opacities,
      the most frequent interstitial abnormality, was related to impaired gas
      diffusion. Bronchiectasis was found in more than half, but only severe
      bronchiectasis was related to airway obstruction. Since bronchial wall thickening
      and linear and/or irregular opacities are both frequent and important
      determinants of impaired pulmonary function, more attention should be given to
      these features in the follow up of CVID patients.

PMID- 19181509
TI  - Acute exacerbation of interstitial pneumonia associated with collagen vascular
      diseases.
AB  - BACKGROUND: Acute exacerbation (AE) is currently established as a distinct
      condition with acute deterioration of respiratory status in idiopathic pulmonary
      fibrosis (IPF). Recently, several studies have reported that AE also occurred in
      interstitial pneumonias other than IPF, such as collagen vascular disease
      associated interstitial pneumonia (CVD-IP). However, the incidence of AE in CVD
      IP and its clinical characteristics remain to be fully determined. This study was
      conducted to elucidate cumulative incidence of AE in CVD-IP and its clinical
      features. METHODS: We reviewed 83 biopsy-proven CVD-IP patients, estimated
      cumulative incidence of AE, and examined its clinical characteristics. RESULTS:
      Among 83 CVD-IP patients, six patients with a mean age of 65.7 years developed AE
      (overall incidence, 7.2%; 1-year incidence, 1.25%). Underlying CVDs included
      rheumatoid arthritis (RA) (n=5; overall incidence, 20.0%) and primary Sjogren
      syndrome (n=1; overall incidence, 5.9%). Patients with AE showed acute
      respiratory deterioration with severe hypoxemia (mean PaO(2)/FiO(2) ratio, 131).
      Radiologically, ground-glass opacity was superimposed on the underlying reticular
      abnormalities. Preexisting histological patterns included three usual
      interstitial pneumonia (UIP) and two non-specific interstitial pneumonia (NSIP).
      Five (83.3%) of six patients died of respiratory failure despite intensive
      therapy. Univariate Cox's proportional hazards analysis showed that age and RA
      diagnosis were significantly associated with AE. Multivariate Cox's proportional
      hazards analysis indicated that age was an independent significant factor
      predicting AE. CONCLUSIONS: These data suggest that AE can occur in CVD-IP, and
      this condition is closely similar to that of IPF with poor prognosis. AE is most
      common in RA, and associated with higher ages.

PMID- 19181510
TI  - An interdisciplinary analysis of sex and gender in relation to the pathogenesis
      of bronchial asthma.
AB  - BACKGROUND: An increasing number of studies confirm that pathogenesis and
      prevalence of bronchial asthma are age and sex dependent. Detailed physiological
      mechanisms of the changing sex ratios with age are not fully known, however, the
      gender (socio-cultural) factors are also imperative. Although multiple factors
      definitely influence the pathogenesis of asthma, only individual or few
      combinations of these have been investigated. METHODS: The terms 'sex', 'gender'
      and plausible combinations of both were systematically researched in selected
      databases (Medline, Scopus) or other sources, including publications from January
      2000 to June 2007. Generated articles were categorized, either as endogenous or
      exogenous factors influencing the pathogenesis of asthma, and divided into the
      following subgroups: genetic, immunological, hormonal, gynaecological,
      nutritional, and environmental parameters. RESULTS: An increasing number of
      studies investigate the influence of sex and gender in the aetiology, therapy and
      prevention of asthma. While their results are still debatable, others regarding
      its initiation, perpetuation and cessation have been clarified. Recent insights
      into interactions at biomolecular and immunological levels greatly contribute to
      clarifying sex-specific influences. Despite occasional oversimplifications, a
      trend for explanations considering the complex interplay of different factors can
      be observed. This work is in line with this trend and offers explanation models
      from our point of view. CONCLUSIONS: Some disagreements regarding the patho
      physiology, diagnosis, treatment and prevention of asthma still prevail.
      Nevertheless, in order to better appreciate its complexity, openness to and
      persistent consideration for interdisciplinary as well as sex- and gender-related
      factors is required of the medical-research community in future investigations.

PMID- 19181511
TI  - Lung function in 30-year-old alpha-1-antitrypsin-deficient individuals.
AB  - BACKGROUND: Alpha-1-antitrypsin (AAT) deficiency increases the risk of emphysema,
      especially in smokers. In 1972-1974, all 200,000 Swedish new-born infants were
      screened for AAT deficiency and individuals with severe (PiZZ) and moderate
      (PiSZ) deficiency have been followed-up regularly. The aim of the present study
      was to examine their lung function at the age of 30 years, comparing them to a
      group of age-matched control subjects (PiMM) recruited from the general
      population, and to compare current smokers with never-smokers. METHOD: Static and
      dynamic spirometry, including TLC, FRC, RV, VC, FEV(1,)K(CO) and D(L,CO), was
      performed for all participants. All values were expressed as percentages of the
      expected values. FEV(1)/VC was expressed both as percentage of the expected value
      and in absolute numbers. RESULTS: Four of 60 PiZZ, none of 19 PiSZ and 9 of 33
      PiMM participating individuals were current smokers. All Pi groups had a normal
      mean FEV(1). The mean (SD) FEV(1)/VC ratio was 75% (7.4) in the PiZZ smokers and
      84% (5.5) in the PiZZ never-smokers (p<0.01). The mean (SD) K(CO) was 81 (13) in
      the PiZZ smokers and 99 (14) in the PiZZ never-smokers (p<0.05). CONCLUSION: AAT
      deficient individuals identified by neonatal screening have normal lung function
      at the age of 30. The PiZZ smokers had changes in lung function that may be signs
      of early emphysema.

PMID- 19181513
TI  - Controlling the electrochemical deposition of silver onto gold nanoparticles:
      reducing interferences and increasing the sensitivity of magnetoimmuno assays.
AB  - An electrocatalytical method induced by gold nanoparticles in order to improve
      the sensitivity of the magnetoimmunosensing technology is reported.
      Microparamagnetic beads as primary antibodies immobilization platforms and gold
      nanoparticles modified with secondary antibodies as high sensitive
      electrocatalytical labels are used. A built-in magnet carbon electrode allows the
      collection/immobilization on its surface of the microparamagnetic beads with the
      immunological sandwich and gold nanoparticle catalysts attached onto. The
      developed magnetoimmunosensing technology allows the antigen detection with an
      enhanced sensitivity due to the catalytic effect of gold nanoparticles on the
      electroreduction of silver ions. The main parameters that affect the different
      steps of the developed assay are optimized so as to reach a high sensitive
      electrochemical detection of the protein. The low levels of gold nanoparticles
      detected with this method allow the obtaining of a novel immunosensor with low
      protein detection limits (up to 23 fg/mL), with special interest for further
      applications in clinical analysis, food quality and safety as well as other
      industrial applications.

PMID- 19181512
TI  - Transcriptional memory at the nuclear periphery.
AB  - A number of inducible yeast genes are targeted to the nuclear periphery upon
      transcriptional activation. However, when repressed again, the INO1 and GAL1
      genes remain at the nuclear periphery for multiple generations. Retention at the
      nuclear periphery represents a novel type of transcriptional memory; the
      peripherally localized, recently repressed state of GAL1 is activated more
      rapidly than the nucleoplasmically localized long-term repressed state of GAL1.
      This rapid reactivation involves localization at the nuclear periphery, the
      SWI/SNF chromatin remodeling complex, the histone variant H2A.Z and the Gal1
      protein itself. Here, I review what we have learned about this type of
      transcriptional memory in yeast, what remains to be resolved and the challenges
      associated with understanding such epigenetic phenomena.

PMID- 19181514
TI  - Anaesthesia for caesarean section in women with complex cardiac disease: 34 cases
      using the Braun Spinocath spinal catheter.
AB  - BACKGROUND: Cardiac disease in pregnancy is now the leading medical cause of
      maternal mortality in the UK. Whilst anaesthesia has not been the precipitant of
      this morbidity, its safety cannot be taken for granted. Spinal catheter
      anaesthesia, a relatively uncommon choice in obstetric practice, offers the
      potential of maintaining haemodynamic stability through accurate and gradual
      titration of neuraxial blockade. METHODS: Thirty-four women with cardiac disease
      requiring caesarean section were selected for spinal catheter anaesthesia. All
      received invasive arterial pressure measurement but in only two were central
      venous catheters sited. After inserting a 24-gauge Braun Spinocath, spinal
      anaesthesia was induced using diamorphine 300 microg and 0.5% hyperbaric
      bupivacaine in 0.25-mL increments. Technical problems, block quality and
      haemodynamic stability were recorded. RESULTS: Successful anaesthesia was
      achieved in 33 women. Spinal catheterisation proved impossible in one case, but
      the catheter was successfully used to provide epidural anaesthesia. There were no
      conversions to general anaesthesia. Eight women (24%) received supplementation
      with intravenous alfentanil, but all reported high satisfaction. Mild, transient
      hypotension occurred in six women (18%), and there was one case of vasovagal
      syncope induced by rapid exteriorisation of the uterus. Three patients (8.8%)
      experienced post dural puncture headache requiring a blood patch; two had
      received repeat dural puncture during catheter insertion. CONCLUSIONS:
      Incremental spinal catheter anaesthesia offers effective anaesthesia with
      excellent haemodynamic control. Post dural puncture headache is of concern, and
      whilst it may be addressed by product modification, it currently limits
      widespread use of the Braun Spinocath in obstetric practice.

PMID- 19181515
TI  - Cellular senescence: hot or what?
AB  - The phenomenon of replicative senescence was first observed more than 40 years
      ago by Hayflick who noted the inability of cultured human fibroblasts to
      proliferate indefinitely. The recent discovery that cellular senescence is
      triggered by many different activated oncogenes has led to the notion that
      senescence, like oncogene-induced apoptosis, serves as a critical and cell
      autonomous tumor preventive mechanism. Both the DNA damage response and the ARF
      tumor suppressor have been mechanistically implicated in oncogene-induced
      senescence and the relative contributions of, and potential interactions between,
      these two pathways remain subjects of a lively debate. More recently, the
      discovery that cellular senescence can be bypassed during the epithelial
      mesenchymal transition (EMT) that typically accompanies tumor progression, the
      observation that organ fibrosis is controlled by cellular senescence and, most
      noticeably, the mounting evidence linking cellular senescence to inflammation,
      make cellular senescence a still flaming hot subject after all these years.

PMID- 19181516
TI  - The bacteriophage lambda CI protein finds an asymmetric solution.
AB  - The CI protein of bacteriophage lambda (lambdaCI) is both a repressor and
      activator of transcription that has served as a model for understanding how gene
      regulatory proteins work. A dimeric DNA-binding protein, lambdaCI also forms
      higher-order oligomers that allow it to bind cooperatively to both adjacent and
      nonadjacent operator sites within the phage genome. The ability of phage lambda
      to transition efficiently from one program of gene expression to another depends
      upon the formation of these higher-order protein-DNA complexes. A recently
      determined crystal structure of a DNA-bound lambdaCI dimer reveals that the two
      subunits of the dimer adopt different conformations. This unexpected asymmetry
      helps explain how these higher-order complexes are assembled.

PMID- 19181518
TI  - Air filled porosity measurements by air pycnometry in the composting process: a
      review and a correlation analysis.
AB  - Air filled porosity (AFP) appears as the best measure to determine the available
      porosity in a composting material or, in general, in an organic matrix. Several
      methodologies, including theoretical and empirical approaches have been developed
      to estimate AFP. Among them, air pycnometry has been considered the most suitable
      and accurate technique to obtain reliable measures of AFP. In this review, the
      published methodologies to determine AFP by air pycnometry are explained in
      detail, and the main advantages and disadvantages of such methodologies are
      discussed. Also, a massive sampling of several organic wastes and mixtures
      intended for composting has been characterized by air pycnometry, and the
      theoretical and empirical correlations proposed in literature are compared in
      terms of accuracy in AFP measurement. Results obtained show that some theoretical
      correlations are suitable for estimating AFP in the majority of organic wastes
      studied. However, some waste samples need an experimental determination to obtain
      a realistic value of AFP.

PMID- 19181517
TI  - Heat and lime-treatment as effective control methods for E. coli O157:H7 in
      organic wastes.
AB  - Land-application of abattoir wastes is economically appealing and may provide an
      effective means of closing the nutrient cycling loop. This practise is
      constrained, however, by legislation which necessitates pre-treatment to remove
      pathogenic micro-organisms prior to land-spreading. Here we investigated whether
      heat-treatment or lime addition could eliminate Escherichia coli O157:H7 from
      three contrasting abattoir wastes. We found that treatment at 60 degrees C for 10
      min effectively eradicated the organism while treatment for the same length of
      time at 50 degrees C led to 2-4 log reductions, but not a complete kill.
      Temperatures of 72 degrees C induced waste solidification rendering its use
      impractical. The potential for re-growth in heat-treated and untreated wastes was
      also investigated. Survival was significantly greater in heat-treated wastes,
      although the difference was less than half a log unit in magnitude. This effect
      of heat-treatment on pathogen survival appeared to be ameliorated when wastes
      were mixed with soil. No viable E. coli O157:H7 cells were recovered from any
      waste after application of lime (CaO) at a rate of 10 gl(-1), even after
      enrichment. Our results indicate that pasteurisation-style or liming treatments
      may provide a suitable alternative method for reducing pathogen loads in abattoir
      wastes, so that they can be applied to land with minimal biological risk.

PMID- 19181519
TI  - Synthesis and optimization of arylsulfonylpiperazines as a novel class of
      inhibitors of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1).
AB  - The synthesis and SAR of a series of arylsulfonylpiperazine inhibitors of 11beta
      HSD1 are described. Optimization rapidly led to potent, selective, and orally
      bioavailable inhibitors demonstrating efficacy in a cynomolgus monkey ex vivo
      enzyme inhibition model.

PMID- 19181520
TI  - Synthesis and evaluation of novel phosphoramidate prodrugs of 2'-methyl cytidine
      as inhibitors of hepatitis C virus NS5B polymerase.
AB  - A variety of new prodrugs of 2'-methyl cytidine based on acyloxy ethylamino
      phosphoramidates have been synthesized and tested in vitro and in vivo for their
      biological activity. Compared with the parent drug a 10- to 20-fold increase in
      formation of nucleotide triphosphate in rat and human hepatocytes could be
      achieved.

PMID- 19181521
TI  - Design, synthesis, and biological evaluation of 1,5-benzothiazepine-4-one
      derivatives targeting factor VIIa/tissue factor.
AB  - The 1,5-benzothiazepine-4-one scaffold was earlier shown to provide efficient
      protease inhibitors. In this contribution, we describe its use in the design of
      factor VIIa/tissue factor inhibitors. A series containing a scaffold non
      substituted on its aryl part led to compound 20 with an IC(50) of 2.16 microM.
      Following molecular modelling studies of this compound, a second series was
      prepared, which necessitated the synthesis of protected 7- or 8-substituted 1,5
      benzothiazepine-4-one derivatives.

PMID- 19181522
TI  - Beta-lactam-based approach for the chemical programming of aldolase antibody
      38C2.
AB  - Irreversible chemical programming of monoclonal aldolase antibody (mAb) 38C2 has
      been accomplished with beta-lactam-equipped targeting modules. A model study was
      first performed with beta-lactam conjugated to biotin. This conjugate efficiently
      and selectively modified the catalytic site lysine (LysH93) of mAb 38C2. We then
      conjugated a beta-lactam to a cyclic-RGD peptide to chemically program mAb 38C2
      to target integrin receptors alpha(v)beta(3) and alpha(v)beta(5). The chemically
      programmed antibody bound specifically to the isolated integrin receptor proteins
      as well as the integrins expressed on human melanoma cells. This approach
      provides an efficient and versatile solution to irreversible chemical programming
      of aldolase antibodies.

PMID- 19181523
TI  - Studies on depigmenting activities of dihydroxyl benzamide derivatives containing
      adamantane moiety.
AB  - Six diphenolic compounds containing adamantane moiety were synthesized and
      evaluated as potent inhibitors on tyrosinase activity and melanin formation in
      Melan-A cells. The inhibitory activity of 4-adamantyl resorcinol 1 was similar to
      that of 4-n-butyl resorcinol in both assays. However, dihydroxyl benzamide
      derivatives 6a-e showed different inhibitory patterns. All derivatives
      significantly suppressed the cellular melanin formation without tyrosinase
      inhibitory activities. These behaviors indicated that the introduction of amide
      bond changes the binding mode of dihydroxyl groups to tyrosinase. Among
      derivatives, 6d (3,4-dihydroxyl compound) and 6e (2,3-dihydroxyl compound) showed
      stronger inhibitory activities (IC(50)=1.25 microM and 0.73 microM, respectively)
      as compared to 4-n-butyl resorcinol (IC(50)=21.64 microM) and hydroquinone
      (IC(50)=3.97 microM). This study showed that the position of dihydroxyl
      substituent at aromatic ring is important for the intercellular inhibition of
      melanin formation, and also amide linkage and adamantane moiety enhance the
      inhibition.

PMID- 19181524
TI  - N-Hydroxy-1,2-disubstituted-1H-benzimidazol-5-yl acrylamides as novel histone
      deacetylase inhibitors: design, synthesis, SAR studies, and in vivo antitumor
      activity.
AB  - A series of N-hydroxy-1,2-disubstituted-1H-benzimidazol-5-yl acrylamides were
      designed and synthesized as novel HDAC inhibitors. General SAR has been
      established for the substituents at positions 1 and 2, as well as the importance
      of the ethylene group and its attachment to position 5. Optimized compounds are
      much more potent than SAHA in both enzymatic and cellular assays. A
      representative compound, 23 (SB639), has demonstrated antitumor activity in a
      colon cancer xenograft model.

PMID- 19181525
TI  - Discovery of GlyT1 inhibitors with improved pharmacokinetic properties.
AB  - Glycine transporter 1 (GlyT1) represents a novel target for the treatment of
      schizophrenia via the potentiation of glutamatergic NMDA receptors. The discovery
      of 4,4-disubstituted piperidine inhibitors of GlyT1 which exhibit improved
      pharmacokinetic properties, including oral bioavailability, is discussed.

PMID- 19181526
TI  - Discovery of benzothiazole derivatives as efficacious and enterocyte-specific MTP
      inhibitors.
AB  - A series of triamide derivatives bearing a benzothiazole core is shown to be
      potent microsomal triglyceride transfer protein (MTP) inhibitors. In order to
      minimize liver toxicity, these compounds have been optimized to have activity
      only in the enterocytes and have limited systemic bioavailability. Upon oral
      administration, selected analogs within this series have been further
      demonstrated to reduce food intake along with body weight and thereby improve
      glucose homeostasis and insulin sensitivity in a 28-day mice diet-induced obesity
      (DIO) model.

PMID- 19181527
TI  - Synthesis and SAR studies of trisubstituted purinones as potent and selective
      adenosine A2A receptor antagonists.
AB  - A series of trisubstituted purinones was synthesized and evaluated as A(2A)
      receptor antagonists. The A(2A) structure-activity relationships at the three
      substituted positions were studied and selectivity against the A(1) receptor was
      investigated. One antagonist 12o exhibits a K(i) of 9nM in an A(2A) binding
      assay, a K(b) of 18nM in an A(2A) cAMP functional assay, and is 220-fold
      selective over the A(1) receptor.

PMID- 19181528
TI  - When it comes to homology, bad habits die hard.

PMID- 19181529
TI  - Knee stiffness following anterior cruciate ligament reconstruction: the incidence
      and associated factors of knee stiffness following anterior cruciate ligament
      reconstruction.
AB  - We reviewed 100 patients retrospectively following primary ACL reconstruction
      with quadruple hamstring autografts to evaluate the incidence and factors
      associated with postoperative stiffness. Stiffness was defined as any loss of
      motion using the contra-lateral leg as a control. The median delay between injury
      and operation was 15 months. The incidence of stiffness was 12% at 6 months post
      reconstruction. Both incomplete attendance at physiotherapy (p<0.005) and
      previous knee surgery (p<0.005) were the strongest predictors of the stiffness.
      Anterior knee pain was also associated with the stiffness (p<0.029). Factors that
      failed to show a significant association with the stiffness included associated
      MCL sprain at injury (p=0.32), post-injury stiffness (p=1.00) and concomitant
      menisectomy at reconstruction (p=0.54). Timing of surgery also did not appear to
      influence the onset of stiffness (median delays: 29 months for stiff patients; 14
      months for non-stiff patients). The rate of stiffness fell to 5% at 12 months
      postreconstruction, without operative intervention.

PMID- 19181530
TI  - Pharmacodynamics and pharmacokinetics studies of phenoxazinium derivatives for
      antimalarial agent.
AB  - In vivo antimalarial drug candidates screening test was carried out on a series
      of water-soluble 3,7-bis(dialkylamino)phenoxazin-5-ium derivatives. Among them, 3
      (diethylamino)-7-(piperidin-1-yl)phenoxazin-5-ium chloride (SSJ-206) showing
      highest efficacy was chosen for further pharmcodynamics and pharmacokinetics
      study. It was supported from these data that the phenoxazinium salts, SSJ-206,
      would be one of hopeful candidates as an oral antimalarial drug.

PMID- 19181531
TI  - Specificities of calreticulin transacetylase to acetoxy derivatives of 3-alkyl-4
      methylcoumarins: effect on the activation of nitric oxide synthase.
AB  - Calreticulin Transacetylase (CRTAase) catalyzes the transfer of acetyl groups
      from polyphenolic acetates (PAs) to the receptor proteins and modulates their
      biological activities. CRTAase was conveniently assayed by the irreversible
      inhibition of cytosolic glutathione S-transferase (GST) by the model
      acetoxycoumarin, 7,8-diacetoxy-4-methylcoumarin (DAMC). We have studied earlier,
      the influence of acetoxy groups on the benzenoid ring, the effect of reduction of
      double bond at C-3 and C-4 position, the effect of methyl/phenyl group at C-4,
      and the influence of position of carbonyl group with respect to oxygen heteroatom
      in the benzopyran nucleus, for the catalytic activity of CRTAase. In this
      communication, we have extended our previous work; wherein we studied the
      influence of an alkyl group (ethyl, hexyl and decyl) at the C-3 position of the
      acetoxy coumarins on the CRTAase activity. The substitution at C-3 position of
      coumarin nucleus resulted in the reduction of CRTAase activity and related
      effects. Accordingly the formation of NO in platelets by C-3 alkyl substituted
      acetoxy coumarins was found to be much less compared to the unsubstituted
      analogs. In addition the alkyl substitution at C-3 position exhibited the
      tendency to form radicals other than NO.

PMID- 19181532
TI  - Synthesis, radiosynthesis, and in vitro evaluation of [131I]-5-iodo-N-[2-(6,7
      dimethoxy-3,4-dihydro-1H-isoquinoline-2-yl)-ethyl]-2-methoxy-benzamide as a
      potential tumor imaging agent.
AB  - This work reports the synthesis, radiolabeling and preliminary in vitro
      evaluation of [(131)I]-5-iodo-N-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2
      yl)-ethyl]-2-methoxy-benzamide. The tributylstannylprecursor was synthesized with
      a yield of 38%. Radiolabeling was performed using an electrophilic
      iododestannylation. Tracer yield was 94%, radiochemical purity was >95%. The
      tracer showed high uptake in MCF-7 breast cancer cell line and therefore will be
      evaluated further.

PMID- 19181533
TI  - High efficiency production and purification of 86Y based on electrochemical
      separation.
AB  - As an intermediate half-life positron emitter (86)Y is an attractive radioisotope
      for positron emission tomography (PET) studies, particularly for patient specific
      dosimetry planning of (90)Y-based radiotherapy procedures. It can be conveniently
      produced by a small-sized cyclotron via the (86)Sr(p,n)(86)Y nuclear reaction.
      The optimization of the electrochemical separation of (86)Y from the target
      material and its purification was done by modeling the whole production cycle
      using (90)Y. The radionuclide was isolated using four electrodes in two
      electrolytic steps. In the first step two Pt plate anodes and a Pt Winkler
      cathode were used and the electro-deposition yield was determined in constant
      current mode of operation. In addition, the influence of pH on the efficiency of
      this first step was investigated. The second electrolysis, with Winkler electrode
      as anode and a Pt wire as cathode, was also performed in constant current mode of
      operation. The kinetics of recovery of the deposited activity on the Pt wire was
      investigated in acidic solutions. The optimized electrochemical method was then
      applied for (86)Y separation and purification. This modified procedure was proved
      to be faster and simpler than the previously proposed electrochemical techniques
      and is more convenient for automation of the routine production of (86)Y.

PMID- 19181534
TI  - BN-PAGE analysis of the respiratory chain complexes in mitochondria of cucumber
      MSC16 mutant.
AB  - Rearrangements of mitochondrial DNA in MSC16 mutant of cucumber (Cucumis sativus
      L.) affect mitochondrial functioning due to the alteration mainly of Complex I
      resulting in several metabolic changes. One-dimensional Blue-Native
      polyacrylamide gel electrophoresis (BN-PAGE) and densitometric measurements
      showed that the level and in-gel capacity of Complex I were lower in MSC16 leaf
      and root mitochondria as compared to wild-type (WT). The level and capacity of
      supercomplex I+III(2) were always lower in leaf but not in MSC16 root
      mitochondria. Two-dimensional BN/SDS-PAGE indicated that the band abundance for
      most of the subunits of Complex I was lower in MSC16 leaf and root mitochondria.
      Supercomplex I+III(2) level was only altered in MSC16 leaf mitochondria as
      measured after 2D BN/SDS-PAGE. No differences in the qualitative composition of
      the subunits of Complex I and supercomplex I+III(2) between MSC16 and WT
      mitochondria were observed. In MSC16 mitochondria Complex I impairment could be
      compensated to some extent by additional respiratory chain NADH dehydrogenases. A
      higher capacity and level of NDB-1 protein of external NADH dehydrogenase was
      observed in MSC16 leaf and root mitochondria as compared to WT. The level of COX
      II, mitochondrial-encoded subunit of Complex IV, was higher in MSC16 leaf and
      root mitochondria. However, the capacity of Complex IV was slightly higher only
      in MSC16 leaf mitochondria. The levels of complexes: III(2) and V and Complex V
      capacity did not differ in mitochondria between genotypes. An abundance of the
      subunits of respiratory complexes is one of the key factors determining not only
      their structure and functional stability but also a formation of the
      supercomplexes. We discuss here mitochondrial genome rearrangements in MSC16
      mutant in a relation to assembly and/or stability (the lower level and capacity)
      of Complex I and supercomplex I+III(2).

PMID- 19181535
TI  - Activation of galactolipid biosynthesis in development of pistils and pollen
      tubes.
AB  - Galactolipids such as monogalactosyldiacylglycerol and digalactosyldiacylglycerol
      are essential lipids for the proper functioning of photosynthetic membranes.
      However, the function of galactolipids in flowers is unknown. Previously, we
      reported that pistils have higher galactolipid-producing activity than leaves.
      The present study investigated galactolipid biosynthesis in pistils in more
      detail using Petunia hybrida and Lilium longiflorum. The results showed that
      digalactosyldiacylglycerol levels increased during flower development. In
      addition, the galactose incorporation activity into galactolipids was induced,
      suggesting that the pathway for the production of digalactosyldiacylglycerol was
      stimulated. Interestingly, a significant increase in galactolipids was also
      observed in elongated pollen tubes. Therefore, pistils are the main site of
      galactolipid biosynthesis and whose galactolipid biosynthesis activity is induced
      during flower development, and this induction includes considerable galactolipid
      biosynthesis in pollen tubes.

PMID- 19181537
TI  - Experimental design should be regulated for the study.

PMID- 19181538
TI  - Transition to intensive care nursing--a national approach?

PMID- 19181539
TI  - Fat synthesis and adiposity regulation in Caenorhabditis elegans.
AB  - Understanding the regulation of fat synthesis and the consequences of its
      misregulation is of profound significance for managing the obesity epidemic and
      developing obesity therapeutics. Recent work in the roundworm Caenorhabditis
      elegans has revealed the importance of evolutionarily conserved pathways of fat
      synthesis and nutrient sensing in adiposity regulation. The powerful combination
      of mutational and reverse genetic analysis, genomics, lipid analysis, and cell
      specific expression studies enables dissection of complicated pathways at the
      level of a whole organism. This review summarizes recent studies in C. elegans
      that offer insights into the regulation of adiposity by conserved transcription
      factors, insulin and growth factor signaling, and unsaturated fatty acid
      synthesis. Increased understanding of fat-storage pathways might lead to future
      obesity therapies.

PMID- 19181540
TI  - The high mannose glycans from bovine ribonuclease B isomer characterization by
      ion trap MS.
AB  - Thirteen high mannose isomers have been structurally characterized within three
      glycomers, Man(5)GlcNAc(2), Man(7)GlcNAc(2), and Man(8)GlcNAc(2) released from
      bovine ribonuclease B, six previously unreported. The study was carried out with
      a single ion trap instrument involving no chromatography. Three previously
      characterized isomers from Man(7) and Man(8) (three each) have been identified
      plus one unreported Man(7) isomer. Incomplete alpha-glucosidase activity on the
      Man(6) and Man(7) glycoproteins appears to account for two additional isomeric
      structures. The preeminence of ion traps for detail analysis was further
      demonstrated by resolving three new isomers within the Man(5) glycomer summing to
      the six previously unreported structures in this glycoprotein. All reported
      structures represent a distribution of Golgi processing remnants that fall within
      the Man(9)GlcNAc(2) footprint. Topologies were defined by ion compositions along
      a disassembly pathway while linkage and branching were aided by spectral identity
      in a small oligomer fragment library. Isomers from this glycoprotein appear to
      represent a distribution of Golgi processing remnants, and an alphanumeric
      classification scheme has been devised to identify all products. Although
      numerous analytical strategies have been introduced to identify selected
      components of structure, it has been the continued focus of this and previous
      reports to only build upon protocols that can be integrated into a high
      throughput strategy consistent with automation. Duplication of these and results
      from comparable standards could bring an important analytical focus to
      carbohydrate sequencing that is greatly lacking.

PMID- 19181541
TI  - The rapid fluorescent focus inhibition test is a suitable method for batch
      potency testing of inactivated rabies vaccines.
AB  - The European Pharmacopoeia proposes two methods for potency determination of
      inactivated rabies vaccines for veterinary use: The first one is a classical
      mouse challenge test, which is imprecise, time-consuming, and causes severe
      distress to the test animals. Alternatively, the potency may be determined
      serologically by measuring the neutralizing antibody titers induced after
      vaccination of mice by using a rapid fluorescent focus inhibition test (RFFIT).
      Although this method is faster and less painful for the animals, it is not widely
      used yet, and only little data exist concerning the comparability of both
      methods. We have therefore performed a comparative study, in which we
      demonstrated a good correlation between the challenge test results and the mean
      titers determined by RFFIT. Furthermore, all vaccine batches failing the
      challenge test were also recognized as insufficient in the serological assay.
      This publication further describes the influence of different vaccine
      administration routes on the resulting antibody titers, and it proposes various
      modifications to the serological assay protocol which could improve its overall
      practicability. Finally, we recommend that the serological assay be used for the
      potency testing of inactivated rabies vaccines.

PMID- 19181542
TI  - Meditation, mindfulness and cognitive flexibility.
AB  - This study investigated the link between meditation, self-reported mindfulness
      and cognitive flexibility as well as other attentional functions. It compared a
      group of meditators experienced in mindfulness meditation with a meditation-naive
      control group on measures of Stroop interference and the "d2-concentration and
      endurance test". Overall the results suggest that attentional performance and
      cognitive flexibility are positively related to meditation practice and levels of
      mindfulness. Meditators performed significantly better than non-meditators on all
      measures of attention. Furthermore, self-reported mindfulness was higher in
      meditators than non-meditators and correlations with all attention measures were
      of moderate to high strength. This pattern of results suggests that mindfulness
      is intimately linked to improvements of attentional functions and cognitive
      flexibility. The relevance of these findings for mental balance and well-being
      are discussed.

PMID- 19181544
TI  - Experimental study on inhibitory effects of histone deacetylase inhibitor MS-275
      and TSA on bladder cancer cells.
AB  - OBJECTIVE: To investigate the inhibitory effect of histone deacetylase (HDAC)
      inhibitors (MS-275 and TSA) on T24 human bladder cancer cells in vitro, and
      explore the possible mechanism. METHODS: The MTT assay was employed to evaluate
      the inhibitory effect of MS-275 and TSA on T24 cell growth. FCM was used to
      analyze the variation of T24 cell cycle distribution and the apoptotic ratio
      after T24 cells were treated with MS-275 and TSA. Histone acetylation level was
      detected by Western blot. mRNA expression of p21 WAF1/CIP1, cyclin A, and cyclin
      E was measured by FQ-PCR. Dynamic changes of Bcl-2 and bax expression were
      detected by FCM. RESULTS: MS-275 and TSA inhibited T24 cell growth in a
      concentration and time-dependent manner. Treatment with 4 MUmol/l MS-275 or 0.4
      MUmol/l TSA blocked cell cycling in the G0/G1 phase and induced a significant
      increase in cell apoptosis. MS-275 and TSA significantly increased the level of
      histone acetylation, induced p21CIP1WAF1 mRNA expression, and inhibited cyclin A
      mRNA expression, though no significant effect was observed on cyclin E. Bcl-2
      expression was down-regulated, while bax expression was up-regulated. CONCLUSION:
      HDAC inhibitors can block bladder cancer cell cycle in vitro and induce
      apoptosis. The molecular mechanism may be associated with increased level of
      histone acetylation, down-regulation of p21WAF1/CIP1 expression, up-regulation of
      cyclin A expression, and dynamic change of bcl-2 and bax expression.

PMID- 19181546
TI  - Barking in family dogs: an ethological approach.
AB  - Although it is one of the most conspicuous features of dog behaviour, barking has
      received little attention from ethologists or from an applied perspective. In
      this review, an ethological look is taken at the communicative aspect of dog
      barking. Emerging new research has indicated that in the repertoire of dog
      vocalisations barking has unique features in showing wide ranges of acoustic
      parameters, such as frequency, tonality and rhythmicity. Barking has been shown
      to be context dependent, and provides information for humans about the inner
      state of the dog although there are few indications that barking is used for
      intra-species communication. It is assumed that dog barking emerged through
      selective processes in which human preferences for certain acoustic aspects of
      the vocalisation may have been paramount. A more experiment-oriented approach is
      required for the study of dog vocalisation that could shed light on the possible
      communicative function of these acoustic signals.

PMID- 19181545
TI  - Increase sensitivity in detecting superficial, low grade bladder cancer by
      combination analysis of hypermethylation of E-cadherin, p16, p14, RASSF1A genes
      in urine.
AB  - OBJECTIVES: To identify a better set of DNA methylation markers to detect
      superficial, low grade cancer cell in urine sediment for improving cancer
      treatment, morbidity, and mortality. MATERIALS AND METHODS: Methylation-specific
      PCR (MSP) assay was used to detect promoter hypermethylation in 4 genes (E
      cadherin, p16, p14, and RASSF1A) to identify reliable biomarkers for bladder
      cancer diagnosis in primary tumor DNA and urine sediment DNA from 57 bladder
      cancer patients. Urine DNA was compared with 20 healthy controls. RESULTS: Fifty
      one (90%) tumor DNA and 47 urine DNA (83%) samples from bladder cancer patients
      revealed hypermethylation in at least 1 of the 4 analyzed genes, whereas all
      urine samples from normal controls were negative. The sensitivity of MSP assay
      for detecting E-cadherin, p16, p14 and RASSF1A in tumor cells in voided urine was
      35%, 35%, 33%, and 65%, respectively. Diagnostic sensitivity was 75% for
      combining RASSF1A and p14, and 83% for RASSF1A, p14 and E-cadherin. Urine
      cytology, however, detect only 13 (28%) cases of cancer or suspicious cancer. For
      detecting superficial and invasive bladder tumor, urine cytology revealed a
      sensitivity of 23% (6/26) and 35% (7/20), respectively. In contrast, MSP detected
      hypermethylation in the urine of 80% (37/46) bladder cancer patients. Moreover,
      hypermethylation analysis of E-cadherin, p14 or RASSF1A genes in urine sediment
      DNA detected in 85% (22/26) of superficial, 85% (11/13) of low grade, 75% (15/20)
      of invasive and 79% (26/33) of high grade bladder cancers. Importantly,
      hypermethylation was detected in the urine DNA of 90% (18/20) superficial tumors
      with negative or atypia cytology. CONCLUSIONS: Hypermethylation of E-cadherin,
      p14 or RASSF1A in urine sediment DNA is a potential biomarker for detecting
      superficial, low grade cancer. Besides, hypermethylation of these 3 genes is a
      valuable adjunct diagnostic marker to urine cytology, which can enhance the
      diagnostic accuracy and follow-up treatment of bladder cancer patients.

PMID- 19181547
TI  - The disabling role of fluctuations in physical activity in patients with chronic
      low back pain.
AB  - Patients with chronic low back pain (CLBP) often report a disabling decrease in
      their activity level due to pain. The nature of the association between
      disability, activity, and pain over time is however, unclear. An intriguing issue
      here is whether a high level of pain-related disability is associated with a low
      activity level or are changes in the level of activity over time pain provoking
      and thus more disabling? The objectives of this study were to investigate
      associations between disability, pain intensity, pain-related fear, and
      characteristics of physical activity in patients with CLBP. A total of 42
      patients with CLBP were recruited from the Pain Clinic of the Maastricht
      University Hospital. Each pain patient carried an electronic diary for one week,
      in which questions about current pain intensity, and the level of physical
      activity were completed at 8 moments a day. Disability was scored by the Quebec
      Back Pain Disability Scale (QBPDS), Fear of movement by the Tampa Scale for
      Kinesiophobia (TSK). To explain the level of disability regression analyses were
      performed with disability as dependent variable and pain intensity, pain-related
      fear, and consecutively the level of physical activity in daily life and
      fluctuations in physical activity as independent variables. Results, based on 34
      patients, showed that activity fluctuations (beta=0.373, p<0.05) rather than the
      mean activity level over time (beta=-0.052, ns) contributed significantly in
      explaining disability. The results are discussed in the light of current
      theories, previous research, and clinical implications.

PMID- 19181548
TI  - Early multidisciplinary evaluation and advice was ineffective for whiplash
      associated disorders.
AB  - BACKGROUND: Whiplash is the most common type of injury reported in traffic
      accidents, but the effectiveness of conservative treatment for whiplash lacks
      evidence. AIMS: To assess the effect of early multidisciplinary evaluation and
      advice on the frequency of chronic neck pain three years post-injury in persons
      with minor or moderate traffic injuries. METHODS: In an insurance setting, we
      tested the effect by (1) a risk score matched prospective cohort design, (2) a
      propensity score matched nested case-control design and, (3) a risk and
      propensity score adjusted multivariate analysis in an unmatched prospective
      cohort design. We simulated unobserved risk and propensity factors to evaluate
      the robustness of the results for hidden bias. RESULTS: All three designs showed
      a significantly increased risk for chronic neck pain among those who received the
      intervention compared to those who did not. The relative risks ranged from 1.7
      (95% CI: 1.0-2.6) to 2.6 (95% CI: 1.5-4.0). The results were robust to hidden
      bias. CONCLUSION: The consistency of the findings across the different designs
      strongly suggest that early multidisciplinary evaluation and advice increased the
      risk of having chronic neck pain three years following a minor or moderate
      traffic injury. Literally, the intervention may therefore have done more harm
      than good.

PMID- 19181549
TI  - Optimal decay rate constant estimates from phased array data utilizing joint
      Bayesian analysis.
AB  - Since their initial description, phased array coils have become increasingly
      popular due to their ease of customization for various applications. Numerous
      methods for combining data from individual channels have been proposed that
      attempt to optimize the SNR of the resultant images. One issue that has received
      comparatively little attention is how to apply these combination techniques to a
      series of images obtained from phased array coils that are then analyzed to
      produce quantitative estimates of tissue parameters. Herein, instead of the
      typical goal of maximizing the SNR in a single image, we are interested in
      maximizing the accuracy and precision of parameter estimates that are obtained
      from a series of such images. Our results demonstrate that a joint Bayesian
      analysis offers a "worry free" method for obtaining optimal parameter estimates
      from data generated by multiple coils (channels) from a single object (source).
      We also compare the properties of common channel combination techniques under
      different conditions to the results obtained from the joint Bayesian analysis. If
      the noise variance is constant for all channels, a sensitivity weighted average
      provides parameter estimates equivalent to the joint analysis. If both the noise
      variance and signal intensity are similar in all channels, a simple channel
      average gives an adequate result. However, if the noise variance differs between
      channels, an "ideal weighted" approach should be applied, where data are combined
      after weighting by the channel amplitude divided by the noise variance. Only this
      "ideal weighting" provides results similar to the automatic-weighting inherent in
      the joint Bayesian approach.

PMID- 19181551
TI  - Analysis of ISCD-NIST survey for bone health.
AB  - In 2007, the National Institute of Standards and Technology and the International
      Society for Clinical Densitometry designed a survey to prioritize 7 research and
      standardization action items to improve accuracy and cross-comparability of dual
      energy X-ray absorptiometry (DXA) measurements of bone mineral density. In this
      article, we analyze the 1074 survey responses as one means to define consensus
      priorities of the community studying bone health and to determine possible
      correlations between prioritization and demographic data, including geographic
      location, years of experience practicing DXA, and medical specialty. We find that
      the distribution of ranks from all respondents is such that we can conclude with
      statistical confidence that there are perceived distinctions between the relative
      merits of the 7 action items. Applying a standard vote-counting rule to the data,
      we determine a complete ranking of the action items. We observe that a consistent
      ranking of each action item across all demographic subcategories is hard to
      achieve. When we arrange the 7 action items into 4 groups, however, we can
      determine a reasonably consistent prioritization. The group containing the
      development of standard reference databases and phantoms receives the highest
      priority. In addition, we report consistent themes that emerge from the free
      response portion of the survey.

PMID- 19181552
TI  - Is the NHANES III femoral neck database discordant with the total hip and
      trochanteric region databases?
AB  - The results of dual-energy X-ray absorptiometry (DXA) testing frequently leads to
      a significant clinical treatment decision, based on T-score or Z-score results.
      Using the nearly universally accepted World Health Organization (WHO) criteria,
      which in turn are based on the validity of the population database, a flawed
      database may lead to an incorrect and deleterious clinical categorization. We
      have observed that the Hologic National Health and Nutrition Examination Survey
      III (NHANES III) femoral neck scores are frequently disproportionately low
      compared with scores in the other major hip regions and that the discordance is
      statistically significant. Although the WHO now uses the femoral neck T-score (in
      postmenopausal women and men 50 yr or older), many clinicians still use the
      lowest (worst) T-score in any 1 of 3 major scan regions--femoral neck, total hip,
      or lumbar spine--suggesting that patient misclassification may occur, leading to
      the potential for unnecessary pharmacologic intervention.

PMID- 19181553
TI  - Evaluation of the potential use of trabecular bone score to complement bone
      mineral density in the diagnosis of osteoporosis: a preliminary spine BMD
      matched, case-control study.
AB  - The trabecular bone score (TBS) is a new parameter that is determined from gray
      level analysis of dual-energy X-ray absorptiometry (DXA) images. It relies on the
      mean thickness and volume fraction of trabecular bone microarchitecture. This was
      a preliminary case-control study to evaluate the potential diagnostic value of
      TBS as a complement to bone mineral density (BMD), by comparing postmenopausal
      women with and without fractures. The sample consisted of 45 women with
      osteoporotic fractures (5 hip fractures, 20 vertebral fractures, and 20 other
      types of fracture) and 155 women without a fracture. Stratification was
      performed, taking into account each type of fracture (except hip), and women with
      and without fractures were matched for age and spine BMD. BMD and TBS were
      measured at the total spine. TBS measured at the total spine revealed a
      significant difference between the fracture and age- and spine BMD-matched
      nonfracture group, when considering all types of fractures and vertebral
      fractures. In these cases, the diagnostic value of the combination of BMD and TBS
      likely will be higher compared with that of BMD alone. TBS, as evaluated from
      standard DXA scans directly, potentially complements BMD in the detection of
      osteoporotic fractures. Prospective studies are necessary to fully evaluate the
      potential role of TBS as a complementary risk factor for fracture.

PMID- 19181554
TI  - Data acquisition analysis for femoral morphometric X-ray absorptiometry.
AB  - Bone mineral density (BMD) is a contributing factor of hip fracture risk. Other
      factors, such as lifestyle, the propensity for falls, and femoral geometry may
      influence the risk of hip fracture. The DMS Lexxos densitometer, a dual-energy X
      ray densitometer can produce either a single-energy X-ray or a BMD image. The
      purpose of this study was to evaluate which of these 2 images enables the best
      detection to make femoral morphometry measurements. Spatial resolution, contrast,
      and noise were evaluated separately. A contrast-detail phantom was also used for
      the purpose of overall visual analysis. The spatial resolution was the same in
      the 2 images. The contrast was better with the BMD image, but the noise was
      higher. Using the contrast-detail phantom, the single-energy X-ray image allowed
      globally a better detection of the objects, but results were in the same range
      with high contrast values. Hip volunteers' morphometric measurements and the
      Singh Index were evaluated 3 times for each image by 3 observers, and the intra-,
      inter-, and global reproducibility was computed. The reproducibility of the
      measurements seems to be better with the single-energy X-ray image but results
      were not statistically significantly different. These results suggest that even
      if the image-quality indices were different, the single-energy X-ray image and
      BMD image are closely useful for clinical morphometric femoral evaluation.

PMID- 19181555
TI  - GS2 as a retinol transacylase and as a catalytic dyad independent regulator of
      retinylester accretion.
AB  - GS2 (PNPLA4; iPLAeta) is the smallest member of the patatin-like family of
      phospholipases (PNPLA). It was initially identified by its ability to hydrolyze
      retinylesters (RE) in cell homogenates, and was later found to esterify retinol
      using a variety of acyl donors. In the present study we set out to determine its
      cellular function and examined its impact on RE status in 293T cells transfected
      with GS2, GS2-M1 (a non-translatable mutant of GS2) and empty vector, in
      fibroblasts isolated from normal and GS2-null donors and in SCC12b and in a
      somatic cell knock-out of GS2 (SCC12b-GS2(neo/-)), that we generated by
      homologous recombination. At 50nM medium retinol, GS2 had no significant impact
      on RE accumulation. However, at 2muM retinol, GS2 promoted a 1.6- to 5-fold
      increase in RE accumulation. To verify role of GS2 as a catalyst, RE levels were
      measured in 293T transfected wild type GS2, catalytic dyad mutants devoid of
      enzymatic activity, or alanine substitution mutants spanning the entire GS2
      sequence. Surprisingly, every GS2 mutant promoted RE accumulation. This activity
      was also observed in the GS2 paralogues and rat orthologue. The data demonstrate
      that within the context of the cell GS2 promotes RE accumulation and may do so
      either as a catalyst or as a regulatory protein that enhances RE formation
      catalyzed by other acyl transferases.

PMID- 19181556
TI  - Molecular interaction of imino sugars with human alpha-galactosidase: Insight
      into the mechanism of complex formation and pharmacological chaperone action in
      Fabry disease.
AB  - Enzyme enhancement therapy (EET) for Fabry disease involving imino sugars has
      been developed and attracted interest. It is thought that imino sugars act as
      pharmacological chaperones for wild-type and mutant alpha-galactosidases (GLAs)
      in cells, but the mechanisms underlying the molecular interactions between the
      imino sugars and the enzyme have not been clarified yet. We examined various
      kinds of imino sugars and found that galactostatin bisulfite (GBS) inhibited GLA
      in vitro and increased the enzyme activity in cultured Fabry fibroblasts as in
      the case of 1-deoxygalactonojirimycin (DGJ). Then, we analyzed the molecular
      interactions between the imino sugars and recombinant human GLA by means of
      isothermal titration calorimetry and surface plasmon resonance biosensor assays,
      and first determined the thermodynamic and binding-kinetics parameters of imino
      sugar and GLA complex formation. The results revealed that DGJ bound to the
      enzyme more strongly than GBS, the binding of DGJ to the enzyme protein being
      enthalpy-driven. In the case of GBS, the reaction was mainly enthalpy-driven, but
      there was a possibility that entropy-driven factors were involved in the binding.
      Structural analysis in silico revealed that both the chemicals fit into the
      active-site pocket and undergo hydrogen bonding with residues comprising the
      active-site pocket including the catalytic ones. The side chain of GBS was
      oriented towards the entrance of the active-site pocket, and thus it could be in
      contact with residues comprising the wall of the active-site pocket.
      Thermodynamic, kinetic and structural studies should provide us with a lot of
      information for improving EET for Fabry disease.

PMID- 19181557
TI  - Intra-abdominal actinomycetoma in a cat.
AB  - A 5-year-old, female Ragdoll cat was diagnosed with an intra-abdominal mycetoma
      involving the ileocaecal region. Diagnosis was obtained via histopathological
      examination following surgical resection of the mass and an ileocolic
      anastomosis. The initial surgery was complicated by lymphangiectasia, chylous
      abdominal effusion and mild bacterial leakage from the anastomosis site. A
      second, exploratory laparotomy was performed to augment the anastomosis with
      serosal patching and omentalisation and to investigate a cystic structure
      observed on follow-up abdominal ultrasound. Initial amoxycillin clavulanate
      (Clavulox; Pfizer Animal Health) therapy was ineffective, but clindamycin
      (Antirobe; Pfizer Animal Health) proved successful in resolving the infection.
      Abdominal actinomycetoma in the cat may be an under-diagnosed condition due to
      its close resemblance to neoplastic disease. Standard diagnostic and therapeutic
      regimens are commonly ineffective in Actinomyces species infections. Surgical
      resection along with adjunctive, long-term, selective antimicrobial therapy is
      effective and prognosis is good for localised lesions.

PMID- 19181558
TI  - Impact of combined and progestogen-only contraceptives on bone mineral density.
AB  - Sex steroids are major determinants of bone mass, and hormonal contraceptives may
      affect bone mineral density (BMD) in women. Combination contraceptives probably
      have no impact on BMD, except perhaps when started within 3 years after the
      menarche. Progestogen-only contraceptives are being increasingly used. Injectable
      medroxyprogesterone acetate, a potent inhibitor of gonadotropin release, can
      induce bone loss, most notably in young women. Other progestogens are used in
      lower doses that have weaker antigonadotropin effects. Levonorgestrel and
      etonorgestrel implants have unclear effects on BMD but are probably safe. The
      impact of high- and low-dose oral progestogens on BMD has not been investigated,
      although no adverse effects would be expected.

PMID- 19181559
TI  - An efficient ultrasound-promoted synthesis of the Baylis-Hillman adducts
      catalyzed by imidazole and L-proline.
AB  - A convenient protocol was developed for the synthesis of the Baylis-Hillman
      adducts in the presence of weak Lewis base and l-proline at room temperature
      under ultrasound irradiation. This method provided the products in good to high
      yields (65-90%) and reasonable reaction times.

PMID- 19181560
TI  - Involuntary emotional expression disorder (IEED) in Parkinson's disease.
AB  - OBJECTIVE: To estimate the frequency and correlates of involuntary emotional
      expression disorder (IEED) in Parkinson's disease (PD) using the Center for
      Neurologic Study-Lability Scale (CNS-LS) and recently-proposed diagnostic
      criteria for IEED. BACKGROUND: IEED is characterized by uncontrollable emotional
      episodes, typically unrelated to or in excess of the underlying mood, and
      occurring with minimal or no stimulus. IEED has been reported to occur in many
      neurological disorders and neurodegenerative diseases, but its prevalence and
      correlates in PD have not been well studied. Additionally, there is no published
      research using recently-proposed IEED diagnostic criteria in any population.
      METHODS: 193 patients with idiopathic PD were assessed with a neuropsychiatric
      battery, including the CNS-LS and the 15-item Geriatric Depression Scale (GDS
      15). A subset (N=100) was also administered a diagnostic interview by a blinded
      rater that applied criteria for both IEED and Diagnostic and Statistical Manual
      of Mental Disorders (DSM-IV-TR) depressive disorders. RESULTS: Applying formal
      diagnostic criteria, 7.0% of patients were diagnosed with IEED, and an additional
      7.0% had subsyndromal IEED symptoms. Applying recommended CNS-LS cutoff scores
      from other populations, either 42.5% (cutoff > or =13) or 16.6% (cutoff > or =17)
      screened positive for IEED. Depressive symptoms were associated with higher CNS
      LS scores (B[SE]=0.27[.08], P=.001) but not with a diagnosis of IEED (odds
      ratio=1.1, [95% CI=1.0-1.3], P=.16). The CNS-LS had poor discriminant validity
      for an IEED diagnosis (AUC=.79, no cutoff value with sensitivity and specificity
      both >60%). CONCLUSIONS: IEED and depression are overlapping but distinct
      disorders in PD. IEED symptoms may occur in up to 15% of PD patients, but a
      disorder occurs in only half of those, suggesting that often IEED symptoms are
      not clinically significant in this population. The CNS-LS does not appear to be a
      good screening instrument for IEED in PD, in part due to its high correlation
      with depressive symptoms.

PMID- 19181561
TI  - Biomechanisms for modelling cerebral cortical folding.
AB  - Understanding the biomechanical mechanisms by which the cerebral cortex folds is
      a fundamental problem in neuroscience. Current mathematical models of cortical
      folding do not include three dimensional geometry or measurement of cortical
      growth in developing brains extracted from experimental data. We present two
      biomechanical models of cortical folding which integrate 3D geometry and
      information taken from MRI scans of fetal sheep brains at a number of key
      developmental stages. The first model utilises diffusion tensor imaging (DTI)
      measurements of white matter fibre orientation in the fetal sheep brains as a cue
      to the tension forces that may regulate folding. In the second model, tangential
      cortical growth is modelled by osmotic expansion of the tissue and regulated by
      inhomogeneous white matter rigidity as a biomechanism of cortical folding. This
      is based on quantitative analysis of cortical growth and inhomogeneous white
      matter anisotropy measured from the MRI data. We demonstrate that structural and
      diffusion tensor MRI can be combined with finite element modelling and an
      explicit growth mechanism of the cortex to create biologically meaningful models
      of the cortical folding process common to higher order mammals.

PMID- 19181562
TI  - Contact lens induced papillary conjunctivitis with silicone hydrogel lenses.
AB  - PURPOSE: To describe the refitting of a soft lens wearer into a silicone hydrogel
      lens due to neovascularization. This change, in turn, caused contact lens induced
      papillary conjunctivitis (CLPC) and a further refitting was necessary. METHODS:
      The patient was refit into a high Dk surface treated silicone hydrogel with a
      high modulus value. A second refitting was undertaken into a lower Dk silicone
      hydrogel contact lens with a lower modulus value which had no surface treatment
      but incorporated an internal wetting agent. RESULTS: A high Dk/t lens was used to
      resolve existing neovascularization and chronic hyperaemia. Subsequently, CLPC
      response occurred, possibly due to a combination of factors, resulting in
      irritation of the palpebral conjunctiva. This resulted in temporary lens
      discontinuation. A second silicone hydrogel lens was fit, along with the use of a
      non-preserved care system, which led to improvement and eventual resolution of
      the condition. CONCLUSION: High Dk silicone hydrogel lenses have shown excellent
      efficacy in resolving hypoxic complications such as neovascularization and
      hyperaemia. However, attention needs to be paid to their potential effect on the
      upper tarsal plate. More than one silicone hydrogel lens may be needed to help
      resolve these issues.

PMID- 19181563
TI  - Corneal staining: do we really understand what we are seeing?
AB  - Sodium fluorescein ('fluorescein') is widely utilised for the evaluation of
      ocular surface integrity. It is particularly well suited to this task due to its
      fluorescent properties and its high visibility at low concentrations. Ocular
      surface fluorescence observed clinically is affected by a number of factors
      including concentration of fluorescein, thickness of the fluorescein layer, the
      wavelength of the exciting light source and whether or not a barrier filter is
      used as part of the viewing system. In this review we have attempted to provide a
      critical evaluation of the published literature relating to three potential
      cellular mechanisms involved in corneal surface fluorescence: surface pooling,
      uptake by cells and ingress around cells. Despite the widespread adoption of use
      of fluorescein for the assessment of the ocular surface, we contend that the
      clinical understanding and interpretation of corneal surface fluorescence is
      based upon assumption, extrapolation and clinical intuition rather than solid
      evidence-based science underpinning the basic causative mechanisms of this
      phenomenon. Further research in order to understand the basic interactions
      between the ocular surface cells and fluorescein should be made a priority in the
      fields of optometry and ophthalmology.

PMID- 19181564
TI  - Corneal shape changes induced by first and second generation silicone hydrogel
      contact lenses in daily wear.
AB  - PURPOSE: To compare the corneal topographical changes induced by two first and
      second generation silicone-hydrogel (SiH) contact lenses after 3 months of daily
      wear (DW). METHODS: Prospective, consecutive case-series in which patients wore
      one of 3 different contact lenses (either the first generation SiH Focus Night &
      Day, the second generation SiH Acuvue Oasys or the monthly disposable Soflens 38
      hydrogel lens as control group) on a DW basis for 3 months. Over-refraction,
      visual acuity, mean keratometry, corneal astigmatism, corneal eccentricity,
      superficial regularity and superficial asymmetry indices were monitored over the
      3-month period. RESULTS: Nineteen eyes of 10 patients completed the study. Seven
      Focus Night & Day, 7 Acuvue Oasys and 5 Soflens 38 contact lenses were fitted.
      There were no significant changes between any of the parameters measured at the 3
      month visit in any of the SiH groups (non-parametric Wilcoxon test, p>0.05).
      However, the control group (Soflens 38) showed statistically significant changes
      regarding mean keratometry, corneal astigmatism and corneal eccentricity
      (p<0.05). Three patients wearing the first generation SiH showed adverse events
      of different degree related to their high modulus of elasticity. CONCLUSIONS:
      After 3 months of DW, wearers of first and second generation SiH lenses showed
      greater corneal stability than hydrogel monthly disposable contact lenses users
      regarding commonly used topographic corneal shape indices. However, complications
      related to the mechanical properties of first generation SiH were seen in three
      patients in the follow-up time.

PMID- 19181565
TI  - The relationship of Central Corneal Thickness (CCT) to Thinnest Central Cornea
      (TCC) in healthy adults.
AB  - PURPOSE: The aim of the study was to precisely quantify the relationship between
      the central corneal points, namely the pupillary centre and the thinnest point in
      the central cornea, in terms of their thickness and location in healthy adults.
      METHODS: 120 eyes of 60 healthy adult volunteers underwent pachymetry with a
      Scheimpflug imaging system (Pentacam). The thickness at the pupillary centre
      (Central Corneal Thickness, CCT) and the thickness at the Thinnest Central
      Corneal (TCC) point were measured. One eye of each patient was used to analyse
      the mean difference between CCT and TCC. Unpaired t-test (one tailed) was used to
      test significance and 95% confidence limits were used. The precise location of
      the TCC in relation to the corneal apex was measured using vector algebraic and
      trigonometric calculations. RESULTS: The mean CCT was 520+/-33microm and the TCC
      was 515+/-36microm. The difference between CCT and TCC was found to be 5.57microm
      (0-15.9microm, 95% CI; P=0.1909). The TCC location was inferotemporal to the
      corneal apex in 58/60 (96.7%) of the right eyes and in 49/60 (81.7%) of the left
      eyes. The average vector location of TCC of both eyes was inferotemporal. This
      coordinate was found to lie 0.62mm (right eye) and 0.79mm (left eye) from the
      corneal apex subtending and angle of 45.5 degrees (right eye) and -10.9 degrees
      (left eye) from the horizontal. CONCLUSION: The study has identified the
      parameters of TCC and its relationship to CCT in terms of the location and
      thickness. For clinical usage, they can be interchangeable as there is no
      significant difference between the two. The consistency in the (inferotemporal)
      location of the TCC merits further research in this regard to the development of
      corneal ectasia.

PMID- 19181566
TI  - Prolonged corneal anaesthesia by proxymetacaine hydrochloride detected by a
      thermal cooling stimulus.
AB  - PURPOSE: To assess the duration, depth and recovery time of anaesthesia produced
      by 0.5% proxymetacaine hydrochloride (proparacaine), using a thermal cooling
      stimulus. METHODS: Seventeen non-contact lens-wearing subjects were recruited
      (mean age=26+/-3.6 years, range=23-39; blue iris=8, brown iris=9). Central
      corneal sensitivity was measured in the right eye of each patient to establish a
      baseline, before 20microl of either 0.5% proxymetacaine hydrochloride (p) or 0.9%
      unpreserved saline (s) was instilled under four experimental conditions (right
      eye-left eye): p-p, p-s, s-p, s-s. Corneal sensitivity was re-measured at 2, 5,
      10, 15, 20, 30, 45 and 60min post-instillation. RESULTS: The onset of anaesthesia
      was observed at 2min (Wilcoxon, p<0.001), with the maximum anaesthesia occurring
      at 15min (Wilcoxon, p<0.001). Recovery of corneal sensitivity to baseline levels
      did not occur by 60min (Wilcoxon, p<0.001). No difference in onset time, depth of
      anaesthesia, or recovery time was noted between the blue and brown iris subjects
      (Mann-Whitney, p>0.05). CONCLUSIONS: Although the anaesthetic effect of 0.5%
      proxymetacaine hydrochloride continues for more than 60min, this finding does not
      alter current clinical practice. The extended duration, however, is of relevance
      to studies that use corneal anaesthesia to investigate the role of corneal nerves
      in the blink mechanism.

PMID- 19181567
TI  - Novel measurements of refractive index, density and mid-infrared integrated band
      strengths for solid O(2), N(2)O and NO(2):N(2)O(4) mixtures.
AB  - We present novel measurements of the refractive index, density and integrated
      band strengths of mid-infrared features of solid N(2)O at 16K and of NO(2) and
      N(2)O(4) in two frozen NO(2):N(2)O(4) mixtures deposited at 16 and 60K. The
      refractive index and density measurements were performed also for frozen O(2)
      deposited at 16K. In this case, the integrated band strength values could not be
      determined since O(2) is a homonuclear molecule and therefore its fundamental
      mode is not infrared active. The solid samples were analysed by infrared
      spectroscopy in the 8000/800cm(-1) range. The sample thickness was measured by
      the interference curve obtained using a He-Ne laser operating at 543nm. The
      refractive index at this laser wavelength was obtained, by numerical methods,
      from the measured amplitude of the interference curve. The density values were
      obtained using the Lorentz-Lorenz relation. Integrated band strength values were
      then obtained by a linear fit of the integrated band intensities plotted versus
      column density values. The astrophysical relevance of these novel measurements is
      briefly discussed.

PMID- 19181568
TI  - A study of the intermolecular interactions of tolmetin/N-acetyl-L-tyrosine ethyl
      ester complex.
AB  - The formation of tolmetin/N-acetyl-l-tyrosine ethyl ester (ATEE) complex has been
      reported by means of both theoretical and experimental studies, including quantum
      mechanical calculations as well as UV-vis absorption, fluorescence and time
      resolved spectroscopy measurements. It has been found that the fluorescence of
      ATEE is quenched due to the formation of a non-fluorescent complex between ATEE
      and tolmetin in the ground state. The geometrical parameters of ATEE/tolmetin
      complex have been determined with the use of the DFT method applying the B3LYP
      correlation-exchange functional and 6-31G(d) basis set. The results of
      experiments indicated the static ATEE quenching by tolmetin. Additionally, the
      experimental and theoretically predicted Gibbs free energy of complexation has
      been calculated.

PMID- 19181569
TI  - Single and multiphase inclusions in metapelitic garnets of the Rhodope
      Metamorphic Province, NE Greece.
AB  - Single and multiphase inclusions in garnet porphyroblasts from the diamond
      bearing pelitic gneisses were studied by means of combined Raman Spectroscopy and
      Electron Scanning Microscopy (SEM/EDX). They are either randomly distributed or
      with preferred orientation within the garnet host and their dimensions vary from
      less than 5 up to 60 microm. In the single-phase inclusions quartz, rutile,
      kyanite and graphite dominate. Biotite, zircon, apatite, monazite and allanite
      are also common. Two types of multiphase inclusions were recognized, hydrous
      silicate (Type I) and silicate-carbonate (Type II) ones. The carbon-bearing
      multiphase inclusions predominantly consist of Mg
      siderite+graphite+CO(2)+muscovite+quartz formed by a high density carboniferous
      fluid rich in Fe, Mg, Si and less Ca, Mn, Al and K trapped in the growing garnet
      in a prograde stage of metamorphism at high-pressure (HP) conditions. The carbon
      free multiphase inclusions predominantly consist of biotite+quartz+rutile+/
      kyanite+muscovite formed through decompression-dehydration/melting reactions of
      pre-existing phengite. Single and multiphase inclusions are characterized by
      polygonal to negative crystal shape formed by dissolution-reprecipitation
      mechanism between the garnet host and the inclusions during the long lasting
      cooling period (>100 Ma) of the Kimi Complex.

PMID- 19181572
TI  - Visual evoked potentials in infants of diabetic mothers: relations to clinical
      and metabolic status during pregnancy and delivery.
AB  - OBJECTIVE: To evaluate Visual Evoked Potentials (VEPs) and psychomotor
      development of infants of diabetic mothers (IDMs) in relation to clinical and
      metabolic data during pregnancy and delivery. METHODS: VEPs and psychomotor
      development (Brunet-Lezine) were analysed in 40 two-month-old IDMs (21 males, 19
      females), 24 from mothers with type-1 diabetes, 13 gestational diabetes, and 3
      type-2 diabetes. Normative VEP data were obtained from 63 age matched controls.
      RESULTS: VEP latencies were significantly longer in IDMs than in controls (O1
      wave IV=197.9+/-35.5 vs 155.3+/-30.3; P<0.001; O2 wave IV=200.2+/-33.8 vs 155.6+/
      29.0; P<0.001). The mean developmental quotient was normal. In IDMs with type-1
      diabetes delayed VEPs were related to increased weight during pregnancy (r 0.516;
      P 0.009), 1st trimester fasting blood glucose (r 0.458; P 0.037), insulin
      requirement during the 2nd (r 0.441; P 0.035) and 3rd trimester (r 0.422; P
      0.039); in IDMs with gestational diabetes, VEP latency showed negative relation
      to Apgar scores (r -0.748; P 0.008). CONCLUSIONS: IDMs have delayed VEPs, which
      may possibly be related to poor metabolic control in pre-gestational diabetes,
      and to delivery complications in gestational diabetes. SIGNIFICANCE: IDMs show
      subtle neurophysiologic changes detectable by VEPs.

PMID- 19181573
TI  - Neurological risks associated with manganese exposure from welding operations--a
      literature review.
AB  - Exposure to manganese dusts and fumes may cause a clinical neurological syndrome
      called manganism. Welders are frequently exposed to manganese-containing fumes
      generated by electric arcs and thermal torches. This paper reviews studies on the
      association between exposure to such welding fumes and neurological disease.
      Using the IRSST expert panel criteria, 78 cases of probable/possible, and 19
      additional cases of possible occupational manganism were identified in the
      literature among manganese-exposed workers involved in welding processes.
      Epidemiological evidence linking welding exposures to Parkinson's disease is
      still controversial. Although more research is needed to clarify the risks of
      neurological impairment from welding, control measures including ventilation and
      adequate respiratory protection, should be implemented to minimize welding fume
      exposures. The significance of fume transport into the central nervous system via
      the olfactory nerve, which by-passes the blood-brain barrier, also needs to be
      assessed.

PMID- 19181570
TI  - The mismatch negativity: a review of underlying mechanisms.
AB  - The mismatch negativity (MMN) is a brain response to violations of a rule,
      established by a sequence of sensory stimuli (typically in the auditory domain)
      [Naatanen R. Attention and brain function. Hillsdale, NJ: Lawrence Erlbaum;
      1992]. The MMN reflects the brain's ability to perform automatic comparisons
      between consecutive stimuli and provides an electrophysiological index of sensory
      learning and perceptual accuracy. Although the MMN has been studied extensively,
      the neurophysiological mechanisms underlying the MMN are not well understood.
      Several hypotheses have been put forward to explain the generation of the MMN;
      amongst these accounts, the "adaptation hypothesis" and the "model adjustment
      hypothesis" have received the most attention. This paper presents a review of
      studies that focus on neuronal mechanisms underlying the MMN generation,
      discusses the two major explanatory hypotheses, and proposes predictive coding as
      a general framework that attempts to unify both.

PMID- 19181574
TI  - Acute intracranial hypertension increases gastric tonus in anesthetized rats.
AB  - We studied the acute effect of intracranial hypertension (ICH) on gastric tonus
      of anesthetized rats. Brain ventricles were cannulated bilaterally for
      intracerebro-ventricular pressure (ICP) monitoring and ICH induction. Next, a
      balloon catheter was inserted at the proximal stomach and coupled to a barostat
      for gastric volume (GV) monitoring by plethysmography. Arterial pressure (AP) and
      heart rate (HR) were monitored continuously during 80-min. After a 20-min basal
      period, they were submitted to control or ICH protocols. In controls, the ICP
      varied spontaneously up to the end. Other rats were subjected to ICP rising to
      10, 20, 40 or 60 mmHg and kept at these levels for 30-min. Another group was
      subjected after basal period to stepwise ICH (ICP rising to 20, 40 and 60 mmHg at
      every 10-min interval). Next, the ICH rats were monitored for further 30-min.
      Other rats, previously submitted to a subdiaphragmatic vagotomy, splanchnicectomy
      plus ganglionectomy or their respective sham surgery, were also studied under
      ICH. Each subset consisted of 5-6 rats. Data were compared to respective basal
      values after ANOVA and Bonferroni's test. In controls, the GV, AP, HR values
      remained within stable levels. Besides inducing bradycardia and arterial
      hypertension, ICH10 mmHg decreased GV by 14.8% at the 50-min interval. In ICH20,
      40 and 60 mmHg subsets, GV decreased 14.0, 24.5 and 30.6% at the 40-min interval,
      respectively. In stepwise ICH rats, GV decreased 10.2% and 12.7%, respectively
      under ICP of 40 and 60 mmHg. The GV values remained significantly lower than
      basal levels during the last 30-min of monitoring. Thus, ICH decreases the GV in
      an ICP-dependent pattern besides inducing Cushing's reflex.

PMID- 19181575
TI  - Abnormal serum tumour markers values do not imply the presence of extra-hepatic
      malignancies in patients with chronic liver disease.

PMID- 19181576
TI  - An unusual skull lesion in a hepatitis B infected patient.

PMID- 19181577
TI  - Comment on "Dynamic response to heat--a novel physical characteristic of breast
      cancer".

PMID- 19181578
TI  - Plastic surgery and burns disasters. What impact do major civilian disasters have
      upon medicine? Bradford City Football Club stadium fire, 1985, King's Cross
      Underground fire, 1987, Piper Alpha offshore oil rig disaster, 1988.
AB  - Major disasters involving multiple casualties are neither new nor infrequent.
      Such events have important implications for medicine and can provide crucial
      lessons for the future. However, while the medical aspects of war have received
      considerable attention, rather less is known about civilian disasters. To redress
      this imbalance, this article reviews three major British disasters of the 1980s
      where serious burns injury was a significant feature of the human casualty: the
      Bradford City Football Club fire of 1985, the King's Cross Underground fire of
      1987 and the Piper Alpha oil rig disaster of 1988. Four related themes are used
      to examine in detail the ways in which these events impacted on medicine:
      plastics and reconstructive surgery, clinical psychology, disaster management and
      long-term structural change. Drawing on articles in specialist burns and
      psychiatric journals, together with the personal communications and recollections
      of surgeons and psychiatrists involved, it is revealed that while ground-breaking
      advances are a relative rarity in medicine, numerous small but significant
      lessons did emerge from these events, although often in subtle and highly
      specialised fields of medicine.

PMID- 19181579
TI  - Shiny-side down is best for foil splints after nailbed repairs.

PMID- 19181580
TI  - Free-style local perforator flaps: concept and classification system.
AB  - BACKGROUND: Defect reconstruction according to the free-style concept applied to
      perforator flaps allows flap harvesting in any anatomical region where an audible
      Doppler signal of a perforator is detected. We report the results of a study in
      which local perforator flaps were selected for reconstruction in different
      anatomical areas and were harvested using the free-style concept. METHODS: During
      a 2-year period, defect coverage was carried out in 21 patients (n=21) in the
      following anatomical areas: cervical (n=3), sternal/parasternal (n=4), axillary
      (n=2), tibial (n=5), trochanteric (n=2) and sacral/gluteal (n=5). The mean age of
      patients (15 male and six female) was 57.8 years. Flap selection was based solely
      on preoperative Doppler mapping in areas adjacent to soft-tissue defects. The
      mean follow-up period was 1 year. RESULTS: All flaps survived, demonstrating
      postoperatively acceptable aesthetic results with good patient satisfaction. The
      donor sites were closed primarily in 17 patients; four patients required skin
      grafting. Two patients required surgical revision due to flap-margin dehiscence.
      There was no loss of function at donor sites. Increased flap mobility could be
      achieved through extended perforator dissection. One perforator-based flaps
      offered the widest arc of rotation serving as propeller flaps. If more than one
      perforator vessel was preserved, flap mobility was limited, but still allowed
      sufficient flap movement either as a rotation or advancement flap or as a
      combination of both. A classification is proposed according to the number of
      perforator vessels preserved and to the type of flap movement. CONCLUSIONS: The
      concept of free-style local perforator flaps represents a safe, versatile and
      reliable surgical procedure. It not only offers a greater freedom in flap
      selection but also provides good aesthetic results. The classification proposed
      might aid in the decision-making process involved in order to achieve adequate
      results with this procedure.

PMID- 19181581
TI  - Impact of hydronephrosis on treatment outcome of solitary proximal ureteral stone
      after extracorporeal shock wave lithotripsy.
AB  - The purpose of this study was to investigate the impact of hydronephrosis on the
      treatment outcome of patients with a solitary proximal ureteral stone after
      extracorporeal shock wave lithotripsy (ESWL). A total of 182 consecutive patients
      who underwent ESWL for a solitary proximal ureteral stone of between 5 and 20 mm
      in size in our institution were included in this study. The degree of
      hydronephrosis was defined by renal ultrasonography. Patient data, stone size,
      shock wave numbers and shock wave energy were also recorded. Treatment outcome
      was evaluated 3 months after the first session of ESWL. In multivariate analysis,
      only the maximal stone length (odds ratio [OR], 0.15; 95% confidence interval
      [CI], 0.03-0.91; p = 0.04) and the degree of hydronephrosis (OR, 0.40; 95% CI,
      0.16-0.98; p = 0.045) were significant predicting factors for stone-free status 3
      months after ESWL. For stones < or = 10 mm, the stone-free rate decreased from
      80% in patients with mild hydronephrosis to 56.4% in those with moderate to
      severe hydronephrosis. For stones > 10 mm, the stone-free rate decreased further,
      from 65.2% in patients with mild hydronephrosis to 33.3% in those with moderate
      to severe hydronephrosis. In summary, patients with a solitary proximal ureteral
      stone and a stone > 10 mm, the treatment outcome after ESWL was not good if
      moderate to severe hydronephrosis was noted on ultrasonography. Alternative
      treatments, such as ureteroscopic lithotripsy, may be appropriate as initial
      treatment or after failure of one session of ESWL.

PMID- 19181582
TI  - Mediators affecting family function in families of children with Duchenne
      muscular dystrophy.
AB  - Most families of children with Duchenne muscular dystrophy (DMD) first receive
      professional information about the disease at the time of their child's
      diagnosis. Generally, as the families begin to build a supportive care system for
      their children, the parents will research DMD on their own or gather formal
      knowledge about the disease from professionals. However, gaining access to care
      is a major challenge because they often do not know how to ask the right
      questions. In particular, vulnerable populations may experience difficulties in
      assisting their child's emotional adjustment to the disability and use of
      available services. The purpose of this study was to test the possible effects of
      psychosocial mediators of parental health, family hardiness and family support on
      family function in relation to the age at diagnosis of children with DMD. One
      hundred and twenty-six Taiwanese parents of children with DMD who are members of
      the Taiwan Muscular Dystrophy Association filled out questionnaires. Subjects
      received a phone call before and again within the first week after we mailed them
      a questionnaire, a stamped return-addressed envelope, and a consent form. The
      questionnaires included the Family Hardiness Index, Family Assessment Device,
      Family APGAR, Duke Health Profile and demographic questions. Hierarchical
      multiple regressions were conducted to test whether family hardiness, parental
      health, or family support mediated or moderated the association between age at
      diagnosis and family function. Family hardiness positively mediated the
      association between age at diagnosis and family function. These findings may help
      the design of interventions to develop family hardiness in families of children
      with DMD.

PMID- 19181583
TI  - A water extract of Pueraria lobata inhibited cytotoxicity of enterovirus 71 in a
      human foreskin fibroblast cell line.
AB  - Enterovirus 71 (EV71) can cause brain encephalitis and mortality. However,
      effective vaccines or chemotherapeutic agents are not yet available. We tested
      the hypothesis that Pueraria lobata could inhibit the cytotoxic effect of EV71 in
      a human foreskin fibroblast cell line by the XTT method. Our results showed that
      the water extract of P. lobata could inhibit cytopathy induced by EV71 when given
      before (p < 0.0001), simultaneously with (p < 0.0001), or after viral infection
      (p < 0.0001). Water extract of P. lobata was effective and its minimal
      concentration that inhibited 50% of the cytopathic effect (IC50) was 0.028
      microg/mL. P. lobata was also safe with a selectivity index greater than 107,000.
      Water extract of P. lobata appeared to inhibit viral attachment (p < 0.0001) and
      penetration (p < 0.0001). The anti-EV71 activity of the water extract of P.
      lobata was not mediated by interferons. In conclusion, the water extract of P.
      lobata was effective in the management of the disease induced by EV71 infection.

PMID- 19181584
TI  - Pauci-immune lupus nephritis: a case report.
AB  - A 26-year-old female with systemic lupus erythematosus was admitted because of
      dyspnea and progressive lower extremity edema. Laboratory testing showed blood
      urea nitrogen levels of 147 mg/dL, creatinine of 6.7 mg/dL, serum albumin of 1.7
      g/dL and the daily protein loss was 12.7 g. Her C3 level was 60.4mg/dL and C4
      level was 10.2 mg/dL. The antinuclear antibody titer was 1:320, with a
      homogeneous pattern, but she was negative for anti-dsDNA. ELISA testing for anti
      PR3 antibodies and anti-MPO antibodies were all negative. She was also negative
      for circulating lupus anticoagulant. Renal biopsy revealed diffuse proliferation
      of glomerular cells, but immunofluorescent microscopy showed no immune deposits
      and electron microscopy revealed only scanty electron-dense deposits. She
      received 1 g/day of methylprednisolone intravenously for 3 days, followed by 60
      mg/day of prednisolone. She was discharged with serum creatinine decreased to 4.7
      mg/dL, and a great improvement in dyspnea. Diffuse proliferative lupus nephritis
      that contains little or no subendothelial deposits is rare. The differential
      diagnosis, possible mechanisms and treatment are discussed.

PMID- 19181585
TI  - Extrathoracic bypass of an orifice occlusive lesion in the arch vessels: case
      reports and literature review.
AB  - Arterial occlusive disease of the arch vessels is often associated with flow
      reversal in the vertebral artery of such patients, the so-called subclavian steal
      syndrome. We treated two such cases that were diagnosed based on symptoms,
      physical examination and angiography. In the first case, the occlusive lesion was
      found at the origin of left subclavian artery, while the occlusion was positioned
      at the origin of innominate artery in the second case. A carotid-subclavian and a
      carotid-carotid bypass using 8-mm PTFE grafts were performed, respectively. No
      complications were noted and the patients have retained a symptom-free status
      during a follow-up of 5 years. Taking into account the expense of stenting and
      the patency rate, extrathoracic bypass surgery using a PTFE graft for the
      treatment of orifice occlusive lesions of arch vessels is cheaper and has an
      overall better patency rate. Furthermore, because it is the final choice of
      treatment after percutaneous transluminal angioplasty fails, it should be
      considered as an ideal therapy for lesions at the origin of arch vessels.

PMID- 19181587
TI  - Cytologic diagnosis of primary effusion lymphoma in an HIV-negative patient.
AB  - Primary effusion lymphoma (PEL) is an unusual and rare type of non-Hodgkin's
      lymphoma characterized by lymphomatous effusion of pleural, pericardial or
      peritoneal cavities without lymphadenopathy or organomegaly. It is associated
      with human herpes virus-8 (HHV-8) and occurs most often in immunodeficient
      patients. We present a case of PEL in a 69-year-old male presenting with pleural
      effusion and ascites. Fluid aspiration showed a monomorphic population of
      atypical lymphoid cells, which were medium- to large-sized, with mono- or
      binucleated hyperchromatic nuclei and a small to moderate amount of basophilic
      cytoplasm containing cytoplasmic vesicles. Immunohistochemically, the lymphoid
      cells expressed CD138 and multiple myeloma oncogene 1, were positive for HHV-8,
      and were monoclonal for immunoglobulin heavy chain gene rearrangement. They were
      negative for Epstein-Barr virus by in situ hybridization. Unfortunately, the
      patient died during the first course of chemotherapy with cyclophosphamide,
      vincristine and prednisone.

PMID- 19181586
TI  - Dual-phase 99mTc-MIBI parathyroid imaging reveals synchronous parathyroid adenoma
      and papillary thyroid carcinoma: a case report.
AB  - The possibility of a coincidental appearance of hyperparathyroidism and thyroid
      cancer is not often considered because of its low incidence. Here, we present a
      case of a 49-year-old woman with a parathyroid adenoma coexisting with two sites
      of papillary thyroid carcinoma. Dual-phase 99mTc-methoxyisobutylisonitrile (MIBI)
      parathyroid imaging before the operation correctly visualized the site of the
      parathyroid adenoma. In addition, two papillary thyroid carcinomas showed faint
      uptake of 99mTc-MIBI on delayed image. Total thyroidectomy and parathyroidectomy
      of a solitary parathyroid adenoma were performed. The patient subsequently
      underwent radioiodine-131 ablation and was treated with T4 suppression. This case
      illustrates the need for clinical awareness of concomitant hyperparathyroidism
      and thyroid cancer. Dual-phase 99mTc- MIBI parathyroid imaging may be useful for
      detecting indolent thyroid cancer before it becomes a distinct disease.

PMID- 19181588
TI  - Adrenal schwannoma treated with laparoscopic adrenalectomy: a case report.
AB  - Schwannoma of the adrenal gland is extremely rare. Here, we report a 49-year-old
      patient with an adrenal tumor noted incidentally by abdominal ultrasonography
      while undergoing regular health examination. Retroperitoneal laparoscopic
      adrenalectomy was performed and the schwannoma was diagnosed by histologic
      findings and immunohistochemistry. Five months after surgery, the patient
      remained well and without evidence of recurrence or metastasis.

PMID- 19181589
TI  - Unbalance between apoptosis and proliferation in female genital tract
      malignancies.

PMID- 19181590
TI  - Pancreas transplantation.
AB  - The first successful pancreas transplantation in conjunction with a simultaneous
      kidney transplantation was performed in 1966 by Kelly, Lillehei and others from
      the University of Minnesota. In Taipei Veterans General Hospital, the first
      pancreas transplantation (simultaneously coupled with kidney transplantation) was
      successfully performed on September 19, 2003, and we were qualified to harvest
      and transplant pancreas graft by the Taiwan Department of Health on August 31,
      2007. Currently, pancreas transplantation remains the most effective method of
      establishing physiological and durable normoglycemia for patients with diabetes
      mellitus. The main indication for pancreas transplantation is type 1 diabetes
      with diabetic complications such as nephropathy, retinopathy, neuropathy and
      cardiocerebral vasculopathy, or with frequent life-threatening hypoglycemia or
      hyperglycemia. Pancreas graft survival rate at 1 year was 85% for simultaneous
      pancreas-kidney transplantation, 78% for pancreas-after-kidney transplantation,
      and 76% for pancreas transplantation alone. At 3 years, pancreas graft survival
      rates were at least 62% in all categories.

PMID- 19181591
TI  - Impact of food on hepatic clearance of patients after endoscopic sphincterotomy.
AB  - BACKGROUND: The recurrence rate of common bile duct stones (CBDS) is around 3-21%
      after treatment by endoscopic sphincterotomy (ES). Fatty meal has been shown to
      improve hepatic clearance in both patients with intact gallbladder and post
      cholecystectomy after ES. This study tested the effects of different kinds of
      food on hepatic clearance by using quantitative cholescintigraphy (QC) in
      patients after ES. METHODS: Forty-seven patients after ES with abnormal QC were
      enrolled in our study. Complete ablation of sphincter function was confirmed by
      sphincter of Oddi manometry. Fasting QC was done in every patient shortly after
      normalization of liver function, and then followed with low-fat and fatty-meal
      QC. Each of the 47 subjects was observed for the effect on hepatic clearance at 3
      different levels of treatments (diets and fasting). Additionally, possible
      factors responsible for recurrent CBDS were investigated by means of logistic
      regression. RESULTS: Both fatty and low-fat meals could significantly improve
      hepatic clearance compared with fasting in most patients after ES. But the
      response to food types was individualized. All patients tolerated the meals well.
      There was no significant relationship between the recurrence of CBDS and sex,
      age, intact gallbladder and presence of juxtapapillary diverticulum, CBD size,
      and improvement in hepatic clearance (> or = 5%) by food. CONCLUSION: Both fatty
      and low-fat meals improved hepatic clearance in most of the patients with CBDS
      after ES, but the response to meals was individualized. Therefore, there is no
      need to restrict the amount of fat intake for patients who have undergone ES.

PMID- 19181592
TI  - Priming with rocuronium to accelerate the onset time of cisatracurium during
      intubation.
AB  - BACKGROUND: The priming technique, in which a small dose of nondepolarizing
      muscle relaxant is administered 3-6 minutes before giving the intubation dose,
      can speed up the onset of muscle relaxation in patients with paralysis during
      intubation. We investigated the priming technique and compared 2 different
      priming agents (rocuronium and cisatracurium) at a priming time of 3 minutes and
      its effect on decreasing the onset time of cisatracurium. METHODS: A total of 60
      patients with ASA physical status I-II scheduled for elective surgery were
      enrolled. After induction with propofol and fentanyl, the patients were
      randomized into 1 of 3 groups. Group 1 received rocuronium 0.06 mg/kg as a
      priming dose. Group 2 received cisatracurium 0.01 mg/kg as a priming dose. Group
      3 received normal saline and constituted the control group. After a 3-minute
      priming time, intubation doses of cisatracurium were given (Groups 1 and 2, 0.14
      mg/kg; Group 3, 0.15 mg/kg). First twitch height percentage (T1/T0%; % of
      control) and train-of-four percentage (T4/T1%) were recorded every 10 seconds
      from baseline until T1/T0% reached 0. RESULTS: Rocuronium (Group 1) and
      cisatracurium (Group 2) significantly accelerated the onset of cisatracurium
      (Group 1, 117.0 +/- 29.0 seconds; Group 2, 151.0 +/- 37.5 seconds; Group 3, 221.5
      +/- 36.6 seconds; all p < 0.001). CONCLUSION: Priming with rocuronium or
      cisatracurium for 3 minutes significantly accelerated the onset of cisatracurium.
      Priming with rocuronium for 3 minutes improved the onset time of cisatracurium
      even more than priming with cisatracurium itself.

PMID- 19181593
TI  - Use of screw-rod system in occipitocervical fixation.
AB  - BACKGROUND: This study retrospectively reviewed 9 patients who underwent
      occipitocervical fixation with a newly developed screw-rod fixation system
      between April 2004 and November 2005. The objective was to evaluate the clinical
      result of occipitocervical fixation with the screw-rod fixation system, including
      symptom relief, fusion rate and complications. METHODS: All 9 patients received
      occipitocervical fixation surgery with screw-rod fixation system and autologous
      bone grafts for fusion. Fusion was assessed by plain cervical X-ray films, and
      the myelopathy by Nurick scale. RESULTS: Four males and 5 females were enrolled
      into this study. Mean age was 58.8 years, and mean follow-up period was 15
      months. One female patient experienced surgical site infection with instrument
      pullout 20 months after surgery; she received a second operation for instrument
      revision. The overall fusion rate was 100%. The mean Nurick scores were 3
      preoperatively and 2.1 postoperatively, with advancement of 0.9 points on
      average. Seven of 9 patients experienced pain or myelopathy improvement. There
      were no complications except for the 1 infection mentioned above. CONCLUSION: The
      fusion rate, complication rate and improvement in neurological function of
      occipitocervical fixation surgery using the screw-rod system were comparable to
      those of the widely used wire-rod system and screw-plate system.

PMID- 19181594
TI  - Prenatal diagnosis of extrastructurally abnormal chromosomes: clinical experience
      and literature review.
AB  - BACKGROUND: To evaluate the clinical association of extrastructurally abnormal
      chromosomes (ESACs) with pregnancy outcome based on the cytogenetic
      characteristics of the ESACs. METHODS: We retrospectively reviewed 12 ESAC cases
      identified from 12,991 cases who received genetic amniocentesis between January
      1983 and March 2008. Prenatal ultrasound findings, characteristics of ESACs
      (karyotypes, special features, origin, inheritance) and pregnancy outcomes were
      recorded. RESULTS: The prenatal prevalence of ESACs was 0.092% (12/12,991). Of
      the 12 ESAC cases, all were de novo. Seven (58.3%) originated from nonacrocentric
      chromosomes and the other 5 (41.7%) were from acrocentric chromosomes, with 3
      originating from chromosome 15. Six of the 12 cases (50%) were large ESACs;
      however, the other 6 (50%) were medium to small ESACs. All acrocentric ESACs
      contained dicentric and bisatellite characteristics. Using FISH and SKY
      techniques, the origins of 2 cases (patients 10 and 12) were clearly identified
      to be from chromosomes 15 and 10, respectively. Five of the 12 ESAC cases (41.7%)
      had congenital anomalies found by prenatal ultrasound. All were nonacrocentric in
      origin that were medium (1/5) to large (4/5) in size. After prenatal genetic
      counseling, 8 of the 12 (66.7%) couples opted to terminate the pregnancy. The
      other 4 (33.3%) continued the pregnancy and their babies were delivered at term
      normally and were followed-up, with normal development ranging from 2 to 17
      years. CONCLUSION: With sophisticated cytogenetic characterization and ultrasound
      examination, it is possible to precisely categorize most fetuses with ESACs as
      being either at high risk of abnormality or at a relatively low risk.

PMID- 19181595
TI  - Pure red cell aplasia and hypogammaglobulinemia in a patient with thymoma.
AB  - Both pure red cell aplasia (PRCA) and hypogammaglobulinemia are rarer conditions
      than myasthenia gravis (MG) in thymoma patients. Several articles have discussed
      the relation between PRCA and thymoma or hypogammaglobulinemia and thymoma, and
      their proper treatments. Instances of both PRCA and hypogammaglobulinemia in a
      thymoma patient are few and reported sporadically in the literature. We discuss a
      46-year-old woman with thymoma and simultaneous PRCA and hypogammaglobulinemia
      who achieved complete remission from PRCA after perioperative steroid
      administration and extended thymectomy, and review the literature.

PMID- 19181596
TI  - Sciatica caused by pseudomyxoma peritonei.
AB  - Many etiologies may cause sciatica, and intra-abdominal masses usually affect the
      lumbosacral plexus by local invasion or distal metastases. Lumbosacral plexopathy
      caused by compression of intra-abdominal tumors instead of invasion is rarely
      seen. A 67-year-old woman had a 3-month history of progressive neurogenic
      claudication, lumbago and left L5 radiculopathy with foot drop. Nocturia and
      progressive abdominal distension with voiding dysfunction were also noted.
      Imaging studies showed a huge pelvic mass with severe compression of the left
      lumbosacral trunk. There was no direct invasion of the lumbosacral plexus by the
      pelvic mass noted in the preoperative imaging studies or intraoperative findings.
      Bilateral ovarian borderline mucinous cystic tumor with pseudomyxoma peritonei
      (PMP) was diagnosed, and the sciatica was improved dramatically after subsequent
      abdominal debulking surgery. Although rare, neural compression caused by PMP and
      intra-abdominal masses needs to be considered in the differential diagnosis of
      sciatica.

PMID- 19181597
TI  - Lens siderosis resulting from a tiny missed intralenticular foreign body.
AB  - We report a patient with clinical ocular siderosis at the time of presentation
      but undetectable intraocular foreign body on computed tomography (CT) and
      ultrasonography. A 24-year-old man suffered from right ocular injury when
      hammering metal on metal. Slit-lamp examination revealed a small corneal
      perforating wound and an iris hole, but no intraocular foreign body was found
      under fundus examination. There was also no evidence of intraocular foreign body
      on ultrasonography and orbital CT scan. About 1 month later, lens siderosis with
      cataract formation developed, and the patient received lens extraction with
      intraocular lens implantation. During the operation, a small (< 1 x 1 x 1 mm in
      size) intralenticular foreign body of metal material was found and removed. The
      patient's visual acuity improved from 6/20 to 6/6 on the next day. A patient
      suspected to have intraocular foreign body should be followed-up closely; it is
      better to remove the foreign body before siderosis bulbi occurs.

PMID- 19181598
TI  - Unusual complication of superior mesenteric artery syndrome: spontaneous upper
      gastrointestinal bleeding with hypovolemic shock.
AB  - Superior mesenteric artery (SMA) syndrome is an unusual form of duodenal
      obstruction. Complications of SMA syndrome may sometimes develop and are usually
      associated with marked gastric dilatation, although most complications can be
      corrected by supportive treatment. In this article, we report a case of severe
      SMA syndrome with hypovolemic shock in a 24-year-old man. Multidetector-row
      computed tomography with reconstructed images was performed to establish the
      diagnosis. Spontaneous gastrointestinal bleeding is an extremely uncommon
      complication of SMA syndrome, and emergent surgical intervention was unavoidable
      in our patient. To our knowledge, no other such case has been reported in the
      English-language literature.

PMID- 19181599
TI  - Late migration of threaded wire (schanz screw) from right distal clavicle to the
      cervical spine.
AB  - We report a 49-year-old man who had undergone osteosynthesis to treat right
      distal clavicular fracture with a threaded wire (Schanz screw). The wire could
      not be removed due to its firm fixation within the bone. Eight years later,
      migration of the broken wire to the right 7th cervical vertebra punctured the
      lamina, with no spinal cord injury noted. The threaded wire was extracted from
      the C7 lamina emergently. No complication occurred after pin removal or during
      the 1-year postoperative follow-up.

PMID- 19181600
TI  - Monostotic Vertebral Paget's Disease of the Lumbar Spine.
AB  - Paget's disease in the Far East is quite rare. Age at diagnosis is usually
      greater than 50 years, and the disease typically affects the spine. Most patients
      are usually diagnosed with Paget's disease following radiographic examination for
      other purposes. It usually occurs at multiple vertebral levels, with only 10-25%
      of vertebral Paget's disease being monostotic. The disease rarely causes
      neurologic complications resulting from compression of intraspinal nerve tissue.
      Here, we present 2 cases of monostotic vertebral Paget's disease of the third
      lumbar vertebra. The first patient, who may be the first documented case of
      Paget's disease in the lumbar spine with progressive neurologic deficiency in an
      Asian population, received decompressive laminectomy due to marked spinal
      stenosis with neurologic deficits. The symptoms were greatly relieved following
      surgery, and ambulatory ability was restored. The second patient was diagnosed
      with Paget's disease following surgical biopsy. He remained asymptomatic at the
      most recent follow-up.

PMID- 19181601
TI  - Increasing drug resistance of Mycobacterium tuberculosis in a medical center--
      what about in Taiwan overall?

PMID- 19181602
TI  - Non-alcoholic steatohepatitis: an overview.
AB  - Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of fat
      induced liver injury, ranging from mild steatosis to cirrhosis and liver failure.
      The presence of obesity and insulin resistance is strongly associated with non
      alcoholic fatty liver and a greater risk of advanced disease. We present here a
      review of the mechanisms involved in the pathogenesis of NAFLD, advances in the
      diagnosis, and options for treatment.

PMID- 19181603
TI  - Spontaneous clearance of Helicobacter pylori colonization in patients with
      partial gastrectomy: correlates with operative procedures and duration after
      operation.
AB  - BACKGROUND/PURPOSE: For patients undergoing gastric surgery because of
      complications of peptic ulcers, such as bleeding or perforation in the pre
      Helicobacter pylori eradication era, their infection status was not surveyed or
      it was neglected altogether. Previous reports have shown spontaneous clearance of
      H. pylori in these patients but the determining factors remain ill-defined.
      METHODS: Seventy-six patients with previous partial gastrectomy for complicated
      peptic ulcers were enrolled prospectively. Patients with peptic ulcers but
      without gastrectomy were selected as a control group. Gastric biopsy specimens
      were obtained from each patient for histological H. pylori staining and rapid
      urease test on endoscopic evaluation. Spontaneous clearance of H. pylori
      colonization was defined when patients who were positive for H. pylori prior to
      operation became negative, without eradication treatment. RESULTS: The prevalence
      of H. pylori colonization was significantly lower in patients with partial
      gastrectomy (22.4%, 17/76 vs. 67.1%, 51/76, p < 0.001). There was a trend towards
      decreasing prevalence of H. pylori colonization as time after operation
      increased: 1-15 years, 29.5% (13/44); 16-30 years, 13.6% (3/22); and > 31 years,
      10% (1/10). The spontaneous clearance rate of H. pylori after partial gastrectomy
      was 43% (13/30). The time after operation in the spontaneous clearance group was
      longer than that in those without (20.8 +/- 11.7 vs. 12.1 +/- 11.0 years, p =
      0.048). Billroth-II procedure had a higher bile reflux rate and a lower H. pylori
      infection prevalence than the Billroth-I procedure. CONCLUSION: Spontaneous
      clearance of H. pylori develops in a certain number of patients who undergo
      distal gastrectomy. The clearance rate is related to operative procedures and
      time after operation.

PMID- 19181604
TI  - Plasma transforming growth factor-beta1 level in patients with severe community
      acquired pneumonia and association with disease severity.
AB  - BACKGROUND/PURPOSE: Pro- and anti-inflammatory cytokines, such as interferon
      (IFN)-gamma, interleukin (IL)-6, IL-10, IL-12 and transforming growth factor
      (TGF)-beta1, have been shown to be mediators associated with severe community
      acquired pneumonia (CAP). It is unknown whether plasma TGF-beta1 level can help
      physicians to judge disease severity. In this study, we investigated the value of
      predicting mortality in patients with severe CAP by the plasma levels of IFN
      gamma, IL-6, IL-10, IL-12 and TGF-beta1 on admission day. METHODS: Patients who
      were admitted to the emergency department and soon transferred to the ICU because
      of severe CAP were enrolled in this study. Plasma levels of IFN-gamma, IL-6, IL
      10, IL-12 and TGF-beta1 on the day of admission were determined in 49 survivors
      and 14 non-survivors within 28 days by ELISA. Clinical characteristics were also
      recorded. RESULTS: Plasma IL-6, IL-10 and TGF-beta1 levels on admission were
      significantly different between survivors and non-survivors. Conversely, there
      was no significant difference in plasma IFN-gamma and IL-12 levels between the
      survivors and non-survivors. Furthermore, the plasma TGF-beta1 level was the only
      independent factor associated with mortality. The value of predicting mortality
      in patients with severe CAP was similar for IL-6, IL-10 and TGF-beta1. Plasma IL
      6 level was not related to the Acute Physiology and Chronic Health Evaluation
      (APACHE) II score. However, plasma IL-10 and TGF-beta1 levels were correlated
      with APACHE II score. CONCLUSION: A severity scoring system, including TGF-beta1
      level on admission, may be considered as a useful parameter to predict outcomes
      of patients with severe CAP.

PMID- 19181605
TI  - Deletions of chromosome 1p and 15q are associated with aggressiveness of
      gastrointestinal stromal tumors.
AB  - BACKGROUND/PURPOSE: Site-dependent profiles of chromosome imbalances (CIs) have
      been reported in gastrointestinal stromal tumors (GISTs). However, the role of
      specific CIs in association with metastasis is not clear. METHODS: Thirteen
      resected liver metastatic GISTs, including seven from the stomach and six from
      the small intestine, were analyzed using comparative genomic hybridization (CGH).
      The CIs associated with metastatic risk were assessed by comparing them with
      those identified in our previous study of 25 primary GISTs, including 14 from the
      stomach and 11 from the small intestine. RESULTS: Synchronous detection of liver
      metastasis was found more often in patients with intestinal than gastric GIST
      (5/6 vs. 2/7, p = 0.048). When compared with the primary tumors, the CI profile
      of liver metastases was similar in the intestinal group, but became more complex
      in the gastric group. Deletions of chromosomes 1p and 15q were very common (>
      80%) in primary and metastatic tumors of the intestinal group, and exhibited a
      trend towards increase in the metastatic tumors of the gastric group. Both groups
      had a doubling in the frequency of 22q deletion in the liver metastases, which
      was not significantly different. Other CIs, including 9p deletion, increased
      significantly in the liver metastases of the gastric group, but not in the
      intestinal group. CONCLUSION: Our results, together with clinical findings,
      indicated a CGH profile associated with the intrinsic aggressiveness of the
      GISTs. Deletion of 1p and 15q play a critical role in the acquisition of
      aggressiveness during early GIST development.

PMID- 19181606
TI  - Endoscopic submucosal dissection for gastric epithelial tumors: a multicenter
      study in Taiwan.
AB  - BACKGROUND/PURPOSE: Endoscopic submucosal dissection (ESD) is an advanced
      endoscopic procedure to resect early gastric cancer (EGC). The purpose of this
      study was to determine the effectiveness and complications of ESD for gastric
      epithelial tumors in Taiwan. METHODS: We retrospectively analyzed the efficacy
      and outcome of ESD in patients who received ESD for gastric epithelial tumors
      between June 2004 and August 2007. RESULTS: A total of 70 patients with gastric
      epithelial tumors were treated by ESD. The mean age was 66.5 +/- 12.9 years
      (range, 35-84 years). The mean size of the gastric epithelial tumors was 1.85 +/-
      0.81 cm. The mean size of resected specimens was 3.26 +/- 1.39 cm. The one-piece
      resection rate was 91.4% (64/70). The median operation time was 92.4 minutes. The
      complicating bleeding and perforation rates were 5.7% (4/70) and 4.3% (3/70),
      respectively. Emergency surgery was performed for three patients with
      perforations. The local recurrence rate of gastric cancer was 2.8%. Except for
      one patient who died of congestive heart failure and another who died of stroke,
      the remaining 68 patients (97.1%) survived. CONCLUSION: ESD is a promising local
      curative treatment option for EGC in Taiwan but it still carries risks of
      perforation and bleeding. The education and learning curve of endoscopists will
      improve the outcome of this procedure.

PMID- 19181607
TI  - Chronic and repeated Chlamydophila pneumoniae lung infection can result in
      increasing IL-4 gene expression and thickness of airway subepithelial basement
      membrane in mice.
AB  - BACKGROUND/PURPOSE: Chlamydophila pneumoniae infection has been associated with
      several pulmonary and cardiac diseases. However, it has not been explored for its
      ability to activate the same immunopathologic mechanisms of asthma, namely, a
      predominant Th2 immune response and structural changes that are termed airway
      remodeling. This study evaluated immune responses in the lung and airway
      pathology of BALB/c mice with chronic and repeated C. pneumoniae infections.
      METHODS: Mice were inoculated intranasally with 5 x 10(6) inclusion-forming units
      of C. pneumoniae TWAR strain, and re-inoculated at 14 and 42 days after the
      primary inoculation. Cytokine gene expression in bronchoalveolar lavage (BAL)
      cells was analyzed by RT-PCR on day 70. Airway pathology was also evaluated by
      morphometric measurements. RESULTS: A significant increase of interleukin (IL)-4
      mRNA was detected in BAL cells in infected mice, and a significant increase in
      subepithelial basement membrane thickness of the airways was also noted in
      infected mice as compared with control mice (8.95 +/- 0.28 microm vs. 5.54 +/-
      0.22 microm, p < 0.0001). We further analyzed the correlation between IL-4
      cytokine expression and the increased subepithelial basement membrane thickness
      of airways in infected mice. We found that mice with increased IL-4 mRNA
      expression had significant increases in the thickness of subepithelial basement
      membrane as compared with mice without increased IL-4 mRNA expression (9.87 +/-
      0.51 microm vs. 6.49 +/- 0.52 microm, p < 0.0001). CONCLUSION: It is believed
      that our results demonstrated for the first time that chronic and repeated
      infections with C. pneumoniae increased IL-4 gene expression and thickness of
      airway subepithelial basement membrane in mice.

PMID- 19181608
TI  - Gastroesophageal reflux disease and sleep quality in a Chinese population.
AB  - BACKGROUND/PURPOSE: Although evidence suggests that gastroesophageal reflux
      disease (GERD) may interrupt sleep, the effects of symptomatic and endoscopically
      diagnosed GERD remain elusive because the patient population is heterogeneous.
      Accordingly, we designed a cross-sectional study to assess their association.
      METHODS: Consecutive participants in a routine health examination were enrolled.
      Definition and severity of erosive esophagitis were assessed using the Los
      Angeles classification system. Demographic data, reflux symptoms, sleep quality
      and duration, exercise amount, alcohol consumption, and smoking habits were
      recorded. Factors affecting sleep quality and sleep duration were revealed by a
      polytomous logistic regression analysis. RESULTS: A total of 3663 participants
      were recruited. Subjects with reflux symptoms, female gender, higher body mass
      index, and regular use of hypnotics had poorer sleep quality. Exercise was
      associated with better sleep quality. Either symptomatically or endoscopically,
      GERD did not disturb sleep duration. Among the 3158 asymptomatic patients, those
      with erosive esophagitis were more likely to have poor sleep quality. The risk
      increased with the severity of erosive changes (p = 0.03). CONCLUSION: The
      present study highlights the adverse effect of gastroesophageal reflux on sleep,
      even in the absence of reflux symptoms. This finding has therapeutic implications
      in patients with silent erosive disease, and future trials are warranted.

PMID- 19181609
TI  - Clinical presentation and outcome of hepatic subcapsular fluid collections.
AB  - BACKGROUND/PURPOSE: Bile, blood or pus may rupture into or extend to the hepatic
      subcapsular space, but most descriptions in the literature are from isolated case
      reports. When fluid collections are limited by the size of the subcapsular space,
      they rarely present with abrupt symptoms and signs. We reviewed our experience
      with hepatic subcapsular fluid collections, including diagnostic studies and
      outcome. METHODS: Two radiologists independently assessed imaging database from
      computed tomography (CT) with the letter strings "subcapsule", "subcapsular",
      "liver" or "hepatic". Subcapsular fluid collection was defined as fluid deep in
      the liver capsule and superficial to the liver parenchyma without rupture into
      the peritoneum. The demographic data, clinical presentation, laboratory and
      imaging results, length of hospital stay, final diagnosis, and outcome were
      reviewed and recorded. RESULTS: From January 2002 to December 2004, 60 patients
      (33 males, 27 females; age range, 4-92 years) were diagnosed by CT to have a
      subcapsular fluid accumulation in liver. Etiologies included traumatic hematoma
      in 10, tumor-related hematoma in 18, ruptured liver abscess in 20, biloma in 8,
      and 4 miscellaneous causes. CT typically showed a lenticular-shaped fluid
      collection compressing the liver parenchyma. The fluid accumulation was connected
      in over half the cases to an intrahepatic lesion with a visible tract.
      Conservative management was adequate in 32 patients, while 9 had surgery and 19
      underwent either percutaneous drainage (by CT or ultrasound guidance) or
      transarterial therapy. Of the 60 patients, 49 (82%) survived the episode,
      including all 10 with traumatic hematoma. The shortest mean length of hospital
      stay was 7.8 +/- 6.7 days in the tumor-related hematoma group, and the longest
      was 50.7 +/- 41.7 days in the abscess group. The international normalized ratio
      for coagulation for those who died and those who survived was 1.8 +/- 1.4 and 1.4
      +/- 0.2 respectively (p = 0.027). CONCLUSION: If these fluid collections are
      limited in the subcapsular space, they are rarely associated with abrupt
      hemodynamic instability and usually not lethal. The only characteristic that
      differed significantly between those who died and those who survived was the
      international normalized ratio, meaning that good liver function and normal
      coagulation has the ability to recover from this dismal episode.

PMID- 19181610
TI  - Surgical ligation of patent ductus arteriosus in very-low-birth-weight premature
      infants in the neonatal intensive care unit.
AB  - This study reported our experience of bedside patent ductus arteriosus (PDA)
      ligation for prematurity in the neonatal intensive care unit (NICU). Between
      April 1992 and March 2006, 41 very-low-birth-weight premature infants underwent
      PDA ligation in the NICU. There were 18 male and 23 female infants. The mean
      gestational age and birth weight were 26.9 weeks and 900.9 g, respectively.
      Preoperatively, 25 infants were ventilator-dependent. After operation, there were
      five deaths caused by complications of prematurity. Surgical complications
      occurred in four and all recovered well after treatment. Twenty preoperatively
      intubated babies survived and were extubated at 21.6 +/- 12.7 days
      postoperatively. In conclusion, bedside PDA ligation in the NICU is safe and
      effective. It can avoid transportation of critically ill, very small infants. We
      suggest surgical closure as the primary treatment in very-low-birth-weight
      infants who are ventilator-dependent to avoid the possible complications of
      indomethacin and prolonged intubation.

PMID- 19181611
TI  - Early or late surgical ligation of medical refractory patent ductus arteriosus in
      premature infants.
AB  - Optimal time to surgical ligation of patent ductus arteriosus (PDA) in very-low
      birth-weight (< 1500 g) premature infants remains an area of controversy. We
      compared the outcomes of early or late ligation of medical refractory PDA in very
      low-birth-weight premature infants. Fifty-six infants underwent surgical closure
      of PDA after failure of or having contraindications to medical treatment.
      Thirteen infants were in the early ligation (< or = 14 days) and 43 in the late
      ligation (> 14 days) groups. Basic clinical features, major morbidity of
      prematurity and mortality were compared. Clinical features and major outcomes
      were similar. The early ligation group had earlier onset of symptomatic PDA (5.7
      +/- 1.6 days vs. 8.1 +/- 3.6 days, p = 0.024), and fewer days of total parenteral
      nutrition (TPN) (39.6 +/- 13.9 days vs. 60.4 +/- 31.4 days, p = 0.025) and
      ventilator use (11.1 +/- 6.7 days vs. 18.6 +/- 10.5 days, p = 0.019). Early
      ligation of medical refractory PDA in very-low-birth-weight premature infants
      improves enteral feeding tolerance and reduces TPN and ventilator use, but long
      term benefits need further investigation.

PMID- 19181612
TI  - Concurrent findings of achalasia and duodenal duplication in a Down syndrome
      patient.
AB  - The association between Down syndrome and gastrointestinal anomalies such as
      duodenal and esophageal atresia, tracheoesophageal fistulas, and Hirschsprung's
      disease is well documented. More recently, an association between Down syndrome
      and achalasia was reported. In this report, we describe a 48-year-old woman with
      a history of Down syndrome who presented with dysphagia. Work-up of the dysphagia
      showed not only achalasia but also a duodenal duplication. To our knowledge,
      there have been no reports of Down syndrome associated with duodenal duplication.
      Whether this finding is simply a coincidence or whether duodenal duplication is
      associated with Down syndrome will need to be determined with future studies.

PMID- 19181613
TI  - Influence of dietary Coexposure to benzo(a)pyrene on the biotransformation and
      distribution of 14C-methoxychlor in the channel catfish (Ictalurus punctatus).
AB  - Methoxychlor (MXC) is an organochlorine pesticide whose mono- and bis
      demethylated metabolites, 2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)-1,1,1
      trichloroethane (OH-MXC) and 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane
      (HPTE), respectively, are estrogenic and antiandrogenic. Studies in vitro showed
      that treatment of channel catfish with a polycyclic aromatic hydrocarbon
      increased phase I and phase II metabolism of MXC. To determine the in vivo
      significance, groups of four channel catfish were treated by gavage for 6 days
      with 2 mg/kg (14)C-MXC alone or 2 mg/kg (14)C-MXC and 2 mg/kg benzo(a)pyrene
      (BaP). On day 7, blood and tissue samples were taken for analysis. Hepatic
      ethoxyresorufin O-deethylase activity was 10-fold higher in the BaP-treated
      catfish, indicating CYP1A induction. More MXC-derived radioactivity remained in
      control (42.8 +/- 4.1%) than BaP-induced catfish (28.5 +/- 3.2%), mean percent
      total dose +/- SE. Bile, muscle and fat contained approximately 90% of the
      radioactivity remaining in control and induced catfish. Extraction and
      chromatographic analysis showed that liver contained MXC, OH-MXC, HPTE, and
      glucuronide but not sulfate conjugates of OH-MXC and HPTE. Liver mitochondria
      contained more MXC, OH-MXC, and HPTE than other subcellular fractions. Bile
      contained glucuronides of OH-MXC and HPTE, and hydrolysis of bile gave HPTE and
      both enantiomers of OH-MXC. The muscle, visceral fat, brain and gonads contained
      MXC, OH-MXC, and HPTE in varying proportions, but no conjugates. This study
      showed that catfish coexposed to BaP and MXC retained less MXC and metabolites in
      tissues than those exposed to MXC alone, suggesting that induction enhanced the
      elimination of MXC, and further showed that potentially toxic metabolites of MXC
      were present in the edible tissues.

PMID- 19181615
TI  - Blocking the BK channel impedes acquisition of trace eyeblink conditioning.
AB  - Big-K(+) conductance (BK)-channel mediated fast afterhyperpolarizations (AHPs)
      following action potentials are reduced after eyeblink conditioning. Blocking BK
      channels with paxilline increases evoked firing frequency in vitro and
      spontaneous pyramidal activity in vivo. To examine how increased excitability
      after BK-channel blockade affects learning, rats received bilateral infusions of
      paxilline, saline, or nothing into hippocampal CA1 prior to trace eyeblink
      conditioning. The drug group was slower to acquire the task, but learning was not
      completely impaired. This suggests that nonspecific increases in excitability and
      baseline neuronal firing rates caused by in vivo blockade of the BK channel may
      disrupt correct processing of inputs, thereby impairing hippocampus-dependent
      learning.

PMID- 19181614
TI  - ANIT-induced intrahepatic cholestasis alters hepatobiliary transporter expression
      via Nrf2-dependent and independent signaling.
AB  - Alpha-naphthylisothiocyanate (ANIT) causes intrahepatic cholestasis by injuring
      biliary epithelial cells. Adaptive regulation of hepatobiliary transporter
      expression has been proposed to reduce liver injury during cholestasis. Recently,
      the oxidative stress transcription factor Nrf2 (nf-e2-related factor 2) was shown
      to regulate expression of hepatobiliary transporters. The purpose of this study
      was to determine whether ANIT-induced hepatotoxicity and regulation of
      hepatobiliary transporters are altered in the absence of Nrf2. For this purpose,
      wild-type and Nrf2-null mice were administered ANIT (75 mg/kg po). Surprisingly,
      ANIT-induced hepatotoxicity was similar in both genotypes at 48 h. Accumulation
      of bile acids in serum and liver was lower in Nrf2-null mice compared with wild
      types treated with ANIT. Transporter mRNA profiles differed between wild-type and
      Nrf2-null mice after ANIT. Bsep (bile salt export pump), Mdr2 (multidrug
      resistance gene), and Mrp3 (multidrug resistance-associated protein) efflux
      transporters were increased by ANIT in wild-type, but not in Nrf2-null mice. In
      contrast, mRNA expression of two hepatic uptake transporters, Ntcp (sodium
      taurocholate cotransporting polypeptide) and Oatp1b2 (organic anion transporting
      peptide), were decreased in both genotypes after ANIT, with larger declines in
      Nrf2-null mice. mRNA expression of the transcriptional repressor of Ntcp, small
      heterodimeric partner (SHP), was increased in Nrf2-null mice after ANIT.
      Furthermore, hepatocyte nuclear factor 1alpha (HNF1alpha), which regulates
      Oatp1b2, was downregulated in ANIT-treated Nrf2-null mice. Preferential
      upregulation of SHP and downregulation of HNF1alpha and uptake transporters
      likely explains why Nrf2-null mice exhibited similar injury to wild-types after
      ANIT. A subsequent study revealed that treatment of mice with the Nrf2 activator
      oltipraz protects against ANIT-induced histological injury. Despite compensatory
      changes in Nrf2-null mice to limit ANIT toxicity, pharmacological activation of
      Nrf2 may represent a therapeutic option for intrahepatic cholestasis.

PMID- 19181616
TI  - Stress disrupts context-dependent memory.
AB  - Memory is facilitated when the retrieval context resembles the learning context.
      The brain structures underlying contextual influences on memory are susceptible
      to stress. Whether stress interferes with context-dependent memory is still
      unknown. We exposed healthy adults to stress or a control procedure before they
      learned an object-location task in a room scented with vanilla. Memory was tested
      24 h later, either in the same or in a different context (unfamiliar room without
      the odor). Stress administered prior to encoding abolished the context-dependent
      memory enhancement found in the control group. Thus, these findings represent the
      first demonstration of impaired context-dependent memory following stress.

PMID- 19181619
TI  - Activity-dependent calpain activation plays a critical role in synaptic
      facilitation and post-tetanic potentiation.
AB  - Synaptic facilitation and post-tetanic potentiation (PTP) are believed to
      necessitate active regeneration of the release machinery and supply of synaptic
      vesicles to a ready-releasable site. The prevailing hypothesis assumes that
      synapsins play pivotal roles in these processes. Using a cholinergic synapse
      formed between cultured Aplysia neurons (B2 and MCn), we demonstrate here that
      the calcium-activated protease-calpain serves as a major regulating element in
      the cascade that links electrical activity, elevation of the free intracellular
      calcium concentration, and short-term synaptic enhancements such as facilitation
      and PTP. Our study revealed that calpain inhibitors (calpeptin and MG132)
      transform a facilitating synapse into a depressing one, and reduce its PTP by
      80.6%. Inhibition of CaM kinases, PKA, and MAPK also reduced PTP at this synapse.
      When inhibitors of these kinases were applied together with calpeptin, tetanic
      stimuli led to synaptic depression. We concluded that at this synapse
      facilitation and PTP are mediated mainly by the calpain-dependent processes and
      to a smaller extent by the CaMKs/PKA/MAPK-dependent cascades.

PMID- 19181618
TI  - Boundary conditions for the maintenance of memory by PKMzeta in neocortex.
AB  - We report here that ZIP, a selective inhibitor of the atypical protein kinase C
      isoform PKMzeta, abolishes very long-term conditioned taste aversion (CTA)
      associations in the insular cortex of the behaving rat, at least 3 mo after
      encoding. The effect of ZIP is not replicated by a general serine/threonine
      protein kinase inhibitor that is relatively ineffective toward PKMzeta, is
      independent of the intensity of training and the perceptual quality of the taste
      saccharin (conditioned stimulus, CS), and does not affect the ability of the
      insular cortex to re-encode the same specific CTA association again. The memory
      trace is, however, insensitive to ZIP during or immediately after training. This
      implies that the experience-dependent cellular plasticity mechanism targeted by
      ZIP is established following a brief time window after encoding, consistent with
      the standard period of cellular consolidation, but then, once established, does
      not consolidate further to gain immunity to the amnesic agent. Hence, we conclude
      that PKMzeta is not involved in short-term CTA memory, but is a critical
      component of the cortical machinery that stores long- and very long-term CTA
      memories.

PMID- 19181617
TI  - Ontogeny of odor-LiCl vs. odor-shock learning: similar behaviors but divergent
      ages of functional amygdala emergence.
AB  - Both odor-preference and odor-aversion learning occur in perinatal pups before
      the maturation of brain structures that support this learning in adults. To
      characterize the development of odor learning, we compared three learning
      paradigms: (1) odor-LiCl (0.3M; 1% body weight, ip) and (2) odor-1.2-mA shock
      (hindlimb, 1 sec)--both of which consistently produce odor-aversion learning
      throughout life and (3) odor-0.5-mA shock, which produces an odor preference in
      early life but an odor avoidance as pups mature. Pups were trained at postnatal
      day (PN) 7-8, 12-13, or 23-24, using odor-LiCl and two odor-shock conditioning
      paradigms of odor-0.5-mA shock and odor-1.2-mA shock. Here we show that in the
      youngest pups (PN7-8), odor-preference learning was associated with activity in
      the anterior piriform (olfactory) cortex, while odor-aversion learning was
      associated with activity in the posterior piriform cortex. At PN12-13, when all
      conditioning paradigms produced an odor aversion, the odor-0.5-mA shock, odor-1.2
      mA shock, and odor-LiCl all continued producing learning-associated changes in
      the posterior piriform cortex. However, only odor-0.5-mA shock induced learning
      associated changes within the basolateral amygdala. At weaning (PN23-24), all
      learning paradigms produced learning-associated changes in the posterior piriform
      cortex and basolateral amygdala complex. These results suggest at least two basic
      principles of the development of the neurobiology of learning: (1) Learning that
      appears similar throughout development can be supported by neural systems showing
      very robust developmental changes, and (2) the emergence of amygdala function
      depends on the learning protocol and reinforcement condition being assessed.

PMID- 19181620
TI  - Subjective vs. documented reality: a case study of long-term real-life
      autobiographical memory.
AB  - A young woman was filmed during 2 d of her ordinary life. A few months and then
      again a few years later she was tested for the memory of her experiences in those
      days while undergoing fMRI scanning. As time passed, she came to accept more
      false details as true. After months, activity of a network considered to subserve
      autobiographical memory was correlated with memory confidence rather than with
      accuracy. After years, mainly regions of the temporal pole displayed this
      pattern. These results might reflect a slow process of increased reliance on
      schemata at the expense of accuracy.

PMID- 19181622
TI  - A bistable genetic switch which does not require high co-operativity at the
      promoter: a two-timescale model for the PU.1-GATA-1 interaction.
AB  - The transcription factors PU.1 and GATA-1 antagonize each other in common myeloid
      progenitors and their relative abundance is thought to decide whether the cell
      follows the erythrocyte/megakaryocyte lineage or the granulocyte/macrophage
      lineage. We propose a kinetic model for the PU.1-GATA-1 interaction, analyse its
      phase space and interpret the results of our analysis. The conclusions have
      broader implications for the modelling of cell-fate selection.

PMID- 19181621
TI  - Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object
      recognition memory in adult rats.
AB  - New granule cells are born throughout life in the dentate gyrus of the
      hippocampal formation. Given the fundamental role of the hippocampus in processes
      underlying certain forms of learning and memory, it has been speculated that
      newborn granule cells contribute to cognition. However, previous strategies
      aiming to causally link newborn neurons with hippocampal function used ablation
      strategies that were not exclusive to the hippocampus or that were associated
      with substantial side effects, such as inflammation. We here used a lentiviral
      approach to specifically block neurogenesis in the dentate gyrus of adult male
      rats by inhibiting WNT signaling, which is critically involved in the generation
      of newborn neurons, using a dominant-negative WNT (dnWNT). We found a level
      dependent effect of adult neurogenesis on the long-term retention of spatial
      memory in the water maze task, as rats with substantially reduced levels of
      newborn neurons showed less preference for the target zone in probe trials >2 wk
      after acquisition compared with control rats. Furthermore, animals with strongly
      reduced levels of neurogenesis were impaired in a hippocampus-dependent object
      recognition task. Social transmission of food preference, a behavioral test that
      also depends on hippocampal function, was not affected by knockdown of
      neurogenesis. Here we identified a role for newborn neurons in distinct aspects
      of hippocampal function that will set the ground to further elucidate, using
      experimental and computational strategies, the mechanism by which newborn neurons
      contribute to behavior.

PMID- 19181626
TI  - Model-based imputation approach for data analysis in the presence of non-detects.
AB  - A model-based multiple imputation approach for analyzing sample data with non
      detects is proposed. The imputation approach involves randomly generating
      observations below the detection limit using the detected sample values and then
      analyzing the data using complete sample techniques, along with suitable
      adjustments to account for the imputation. The method is described for the normal
      case and is illustrated for making inferences for constructing prediction limits,
      tolerance limits, for setting an upper bound for an exceedance probability and
      for interval estimation of a log-normal mean. Two imputation approaches are
      investigated in the paper: one uses approximate maximum likelihood estimates
      (MLEs) of the parameters and a second approach uses simple ad hoc estimates that
      were developed for the specific purpose of imputations. The accuracy of the
      approaches is verified using Monte Carlo simulation. Simulation studies show that
      both approaches are very satisfactory for small to moderately large sample sizes,
      but only the MLE-based approach is satisfactory for large sample sizes. The MLE
      based approach can be calibrated to perform very well for large samples.
      Applicability of the method to the log-normal distribution and the gamma
      distribution (via a cube root transformation) is outlined. Simulation studies
      also show that the imputation approach works well for constructing tolerance
      limits and prediction limits for a gamma distribution. The approach is
      illustrated using a few practical examples.

PMID- 19181623
TI  - GlycoFibroTest is a highly performant liver fibrosis biomarker derived from DNA
      sequencer-based serum protein glycomics.
AB  - Liver fibrosis is currently assessed by liver biopsy, a costly and rather
      cumbersome procedure that is unsuitable for frequent patient monitoring, which
      drives research into biomarkers for this purpose. To investigate whether the
      serum N-glycome contains information suitable for this goal, we developed a 96
      well plate-based serum N-glycomics sample preparation protocol that only involves
      fluid transfer steps and incubations in a PCR thermocycler yielding 8-aminopyrene
      1,3,6-trisulfonic acid-labeled N-glycans. These N-glycans are then ready for
      analysis on the capillary electrophoresis-based DNA sequencers that are the
      current standard in clinical genetics laboratories worldwide. Subsequently we
      performed a multicenter, blinded study of 376 consecutive chronic hepatitis C
      virus patients for which liver biopsies and extensive serum biochemistry data
      were available. Among patients, the METAVIR fibrosis stage distribution was as
      follows: 10.6% F0, 44.4% F1, 20.5% F2, 18.4% F3, and 6.1% F4. We found that the
      ratio of two N-glycans, here called GlycoFibroTest, correlates with the
      histological fibrosis stage equally well as FibroTest (rho = 0.4-0.5 in F1-F4),
      which is used in the clinic today. Finally using affinity chromatography we
      depleted sera of immunoglobulin G, and this resulted in a complete removal of the
      undergalactosylated biantennary glycans from the N-glycome, which are partially
      determining GlycoFibroTest.

PMID- 19181627
TI  - Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit
      and is associated with elevated plasma apolipoprotein A-I.
AB  - Carnitine palmitoyltransferase IA, encoded by CPT1A, is a key regulator of fatty
      acid metabolism. Previously, a loss-of-function mutation, namely, c.1436 C-->T
      (p.P479L), was reported in CPT1A in the homozygous state in Canadian aboriginal
      male with presumed CPT1A deficiency. To determine the population frequency of
      this variant, we determined CPT1A p.P479L genotypes in 1111 Greenland Inuit.
      Associations between genotype and variation in plasma total cholesterol,
      triglycerides, LDL, HDL, apolipoprotein (apo) B, and apoA-I was also
      investigated. We found the L479 allele occurs at a high frequency in this sample
      (0.73), while it was completely absent in 285 nonaboriginal samples. This
      suggests that the original proband's symptoms were not likely due to the CPT1A
      p.P479L mutation because it is very common in Inuit and because symptoms
      suggesting CPT1A deficiency have not been reported in any carrier subsequently
      studied. However, CPT1A p.P479L was associated with elevated plasma HDL and apoA
      I levels. The association with increased levels of HDL and apoA-I suggest that
      the polymorphism might protect against atherosclerosis.

PMID- 19181628
TI  - An improved method to determine serine palmitoyltransferase activity.
AB  - Serine palmitoyltransferase (SPT) catalyzes the condensation of l-serine and
      palmitoyl-CoA, which is the rate-limiting step in the de novo synthesis of
      sphingolipids. SPT activity is commonly measured by monitoring the incorporation
      of radiolabeled l-serine into 3-ketodihydrosphingosine. In this article, we
      introduce several adaptations of the established protocol to improve sensitivity,
      reproducibility, and practicability of the assay. A significant improvement of
      this new protocol is the possibility to measure SPT activity in total cell lysate
      instead of microsomes. The assay is furthermore extended by the introduction of a
      nonradioactive, HPLC-based detection protocol. The suggested HPLC method offers
      several advantages, most importantly, a 20-fold lower detection limit compared
      with the radioactive assay and the possibility to use an internal standard to
      correct for variation in the extraction.

PMID- 19181629
TI  - Urinary retention and cystitis associated with subcutaneous estradiol pellets in
      female nude mice.
AB  - Unexpected deaths occurred in studies involving a nude mouse model of mammary
      cancer that required subcutaneous implantation of 0.5 mg twenty-one-day release
      estrogen pellets for growth of the estrogen-dependent mammary tumor xenograft
      BT474c. Early deaths occurred in female nude mice and were associated with
      urinary retention, frequently with cystitis. Drug treatment had no effect on the
      incidence or severity of cystitis. Histological findings did not alter
      significantly over various time points following pellet implantation. Changes
      were not seen in males or in females receiving lower doses of estradiol even when
      the duration of administration was prolonged, suggesting that a threshold level
      was required for the onset of urinary retention. Because of the influence of
      estrogen on micturition, immunohistochemistry for estrogen receptor alpha
      (ERalpha) in the urinary bladder was carried out, which did not demonstrate any
      differences between females implanted with 0.5 mg twenty-one-day release estrogen
      pellets and nonimplanted females. Although previous publications have
      concentrated on possible mechanisms of action, this paper describes the
      histopathological changes seen in the urinary bladder of female nude mice
      resulting from exposure to high levels of estradiol.

PMID- 19181630
TI  - Comparison of histochemical methods for murine eosinophil detection in an RSV
      vaccine-enhanced inflammation model.
AB  - A comparative study of histochemical detection of eosinophils in fixed murine
      tissue is lacking. Five histochemical methods previously reported for eosinophil
      detection were quantitatively and qualitatively compared in an established murine
      RSV vaccine-enhanced inflammation model. Nonspecific neutrophil staining was
      evaluated in tissue sections of neutrophilic soft tissue lesions and bone marrow
      from respective animals. Eosinophils had granular red to orange-red cytoplasmic
      staining, depending on the method, whereas neutrophils had, when stained, a more
      homogenous cytoplasmic pattern. Nonspecific background staining of similar
      coloration was variably seen in vascular walls and erythrocytes. Astra Blue/Vital
      New Red, Congo Red, Luna, Modified Hematoxylin and Eosin, and Sirius Red
      techniques were all effective in detecting increased eosinophil recruitment
      compared to controls; however, differences in eosinophil quantification varied
      significantly between techniques. Astra Blue/Vital New Red had the best
      specificity for differentiating eosinophils and neutrophils but had a reduced
      ability to enumerate eosinophils and was the most time intensive. The Luna stain
      had excessive nonspecific staining of tissues and a reduced enumeration of
      infiltrating eosinophils, which made it suboptimal. For multiple parameters such
      as eosinophil detection, specificity, and contrast with background tissues, the
      Sirius Red followed by Congo Red and Modified Hematoxylin and Eosin methods were
      useful, each with their own staining qualities.

PMID- 19181631
TI  - Venous invasion detection in colorectal cancer: which approach, which technique?
AB  - Colorectal cancer is one of the most commonly diagnosed human malignancies and is
      a major cause of death worldwide. A high-quality macroscopic examination and
      histopathology report enables correct tumour staging, affects patient prognosis,
      and provides indications for further therapy. Although venous invasion is a stage
      independent indicator of poor prognosis that identifies high-risk patients for
      visceral metastases, it is not a stage-influencing factor. Accordingly the use of
      special stains to facilitate the detection of venous invasion is not universally
      recommended and therefore not widely used in routine histopathological analysis.
      In this report based on a case presentation, the different approaches and
      techniques for detecting venous invasion are presented and discussed.

PMID- 19181632
TI  - Development and validation of a zeta-globin-specific ELISA for carrier screening
      of the (--SEA) alpha thalassaemia deletion.
AB  - AIMS: The Southeast Asian (SEA) deletion (--(SEA)) represents the most common
      determinant causing alpha thalassaemia in Southeast Asian countries. The
      embryonic zeta-globin chain has been defined as a marker for the detection of
      this deletion in adults. The aim of this study was to develop an appropriate low
      cost ELISA for zeta-globin chain detection as a routine screening test for (-
      (SEA)) alpha thalassaemia deletion. METHODS: A sandwich ELISA system for zeta
      globin chains was established with a pair of zeta-globin-specific monoclonal
      antibodies prepared in-house, and locally made products. Against a gap-PCR method
      that was taken as the standard, this assay was validated in a cohort study
      testing a total of 526 individuals comprising patients scheduled for
      haemoglobinopathy diagnostic analysis and normal individuals. Routine screening
      of the (--(SEA)) deletion in 300 random student volunteers was conducted using
      the assay. RESULTS: While the cut-off point was set at a percentage positive
      value of 30, the sensitivity and specificity of this ELISA method were 100% and
      99.24%, respectively. The mean intra-assay and inter-assay coefficients of
      variation among the different concentrations in the optimised ELISA conditions
      were 2.1-11.4% and 4.3-13.2%, respectively. Seventeen of the 300 volunteers
      sampled were determined by the ELISA to have the (--(SEA)) deletion; these
      results were in 100% agreement with the gap-PCR results. CONCLUSIONS: This study
      validates the ELISA method described here as a simple, rapid and cost-effective
      assay that is potentially adaptable for application in large-scale population
      screening for this prevalent disorder in SEA areas such as southern China.

PMID- 19181633
TI  - CD105/endoglin expression in Gorham disease of bone.
AB  - BACKGROUND: Gorham disease is a rare pathological condition characterised by a
      proliferation of vascular channels of haematic and lymphatic origin in bone and
      adjacent soft tissues, which results in a progressive destruction of the involved
      bone segment. AIM: To evaluate expression of the vascular endothelial cell marker
      CD105/endoglin in Gorham disease of bone. METHODS: An immunohistochemical
      analysis was conducted on four cases of Gorham disease of bone, and for
      comparison on eight cases of conventional haemangioma of bone and on normal fetal
      and adult bone tissue specimens. RESULTS: Diffuse and intense immunostaining of
      endothelial cells for CD105 was observed in the specimens of fetal bone in areas
      undergoing ossification and in the growth plate of young adults. In medullary
      bone, CD105 positivity was limited to sinusoids of haemopoietic marrow, while
      endothelial cells of capillaries and small arterioles and venules within fatty
      marrow were either negative or showed weak immunostaining. The mean percentage of
      positive vessels in Gorham disease was significantly higher than in osseous
      haemangioma (58.9 (SEM 14.9) vs 17.2 (SEM 12.0); p = 0.03, Mann-Whitney U test).
      A significant direct correlation was observed between the proliferative activity
      assessed by MIB-1 immunostaining, and the percentage of CD105 positive vessels in
      the entire series (r = 0.681; p = 0.01). CONCLUSIONS: Data indicate that the
      phenotype of proliferating endothelial cells of Gorham disease is similar to that
      of the endothelial lining of vessels of metabolically active bone characterised
      by high expression of CD105, while that of conventional haemangioma is more
      similar to that of metabolically quiescent bone tissue, such as fatty marrow,
      with low levels of expression of CD105. This may have potential therapeutic and
      diagnostic applications.

PMID- 19181634
TI  - Self-monitoring of oral anticoagulation: does it work outside trial conditions?
AB  - BACKGROUND: Patient self-monitoring (PSM) of oral anticoagulation therapy (OAT)
      can improve anticoagulant control, but poor uptake and high dropout rates have
      prompted suggestions that PSM is suitable for only a minority of patients in the
      UK. AIMS: To determine whether PSM could be a viable alternative to regular
      hospital anticoagulant clinic attendance, if offered from the start of treatment.
      METHODS: 318 consecutive patients referred, for the first time, to an
      anticoagulation clinic were assessed for eligibility using established criteria.
      Patients electing for PSM attended training and, following successful assessment,
      performed a capillary blood INR every two weeks or more frequently if directed to
      do so by the anticoagulation clinic. Primary outcome measures were uptake of PSM
      and the percentage time in target therapeutic INR range (TIR) compared to
      patients electing for routine clinic care. RESULTS: Of 318 patients referred for
      OAT, 188 were eligible for PSM. 84 (26%) elected to self-monitor, of whom 72
      (23%) remained self-monitoring or had completed their course of treatment at the
      end of the audit. Self-monitoring patients had significantly better anticoagulant
      control than those receiving routine hospital anticoagulation clinic care (TIR
      71% vs 60%, p = 0.003) and significantly less time outside critical limits, ie,
      INR <1.5 or >5.0 (0.45% vs 2.04%, p = 0.008). CONCLUSIONS: Patients offered PSM
      from the start of treatment show increased uptake compared to previous UK studies
      and a level of oral anticoagulation control comparable to that reported in
      previous clinical trials.

PMID- 19181635
TI  - Immunohistochemical analysis of the oxidative phosphorylation complexes in
      skeletal muscle from patients with mitochondrial DNA encoded tRNA gene defects.
AB  - BACKGROUND: Mitochondrial diseases display a heterogeneous spectrum of clinical
      phenotypes and therefore the identification of the underlying gene defect is
      often a difficult task. AIMS: To develop an immunohistochemical approach to stain
      skeletal muscle for the five multi-protein complexes that organise the oxidative
      phosphorylation (OXPHOS) in order to improve the diagnostic workup of
      mitochondrial defects. METHODS: OXPHOS complexes were visualised in skeletal
      muscle tissue using antibodies directed against different subunits. The staining
      patterns of patients with heteroplasmic defects in mtDNA tRNA genes were compared
      with those of normal and disease controls. RESULTS: Normal skeletal muscle
      displayed a checkerboard staining pattern for complexes I to V due to the higher
      mitochondrial content of slow muscle fibres versus fast fibres. In patients with
      tRNA defects, a much more heterogeneous staining pattern was observed for complex
      I (all six patients) and complex IV (4 of 6 patients): a mosaic staining pattern
      in which individual fibres displayed staining intensities that ranged from strong
      to negative. Ragged red fibres (RRFs) in patients with MERRF (myoclonic epilepsy
      and ragged red fibres) were all complex I and IV negative, while in patient with
      MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like
      episodes) the majority of RRFs were complex I negative and complex IV positive.
      CONCLUSION: Immunohistochemical detection of OXPHOS complexes could represent a
      valuable additional diagnostic tool for the evaluation of mitochondrial
      cytopathy. The technique helps to detect heteroplasmic mtDNA defects. Staining
      for complex I in particular was able to identify two tRNA patients that stayed
      undetected with routine histochemical evaluation.

PMID- 19181636
TI  - Intraosseous schwannoma of rib.
AB  - A case of intraosseous schwannoma of rib is presented. A 22-year-old woman was
      admitted with paroxysmal thoracic pain, unproductive cough and a hard mass of the
      thorax. CT scan showed a unilocular osteolystic lesion in the rib. A needle
      biopsy was performed, and a diagnosis of intraosseous schwannoma was made. The
      patient underwent a partial excision of rib and the tumour was removed.
      Macroscopic examination revealed a 4 x 2 x 1.5 cm solid lesion with destruction
      of bone. Microscopically, the tumour showed typical features of schwannoma
      characterised by Antoni A and Antoni B tissues and Verocay bodies.
      Immunohistochemically, the tumour was positive for S-100 protein, vimentin,
      neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP). The
      patient is well without local recurrence or metastasis after a 1-year follow-up.
      This is believed to be the second case report of primary schwannoma of rib.

PMID- 19181637
TI  - A retroperitoneal bronchogenic cyst mimicking adrenal tumour in an adult: is
      differential diagnosis truly possible?
AB  - Bronchogenic cysts are developmental abnormalities of the primitive foregut
      resulting from aberrant budding from the ventral diverticulum. A retroperitoneal
      position for a bronchial cyst is extremely unusual and should be differentiated
      from other neoplastic lesions. Although histologically they can be differentiated
      from other lesions, bronchial cysts may show various pathological patterns of
      differentiation that may cause confusion in differentiating them from cystic
      teratomas. This is a case of a retroperitoneal bronchogenic cyst featuring
      uncommon histological findings, which raises the question whether these benign
      lesions can always be accurately differentiated from teratomatoid cystic
      neoplasms.

PMID- 19181638
TI  - A simultaneous occurrence of Tolosa-Hunt syndrome and fibrillary
      glomerulonephritis: a case report.
AB  - Fibrillary glomerulonephritis (FibGN) is a rare cause of progressive renal
      dysfunction, often leading to dialysis within a few years. A 60-year-old woman
      presented with a 2 month history of right-sided retro-orbital pain and recent
      diplopia. Laboratory testing revealed an altered renal function with increased
      serum creatinine and mild proteinuria. MRI of the brain revealed the presence of
      a soft tissue mass on the right cavernous sinus compatible with the diagnosis of
      Tolosa-Hunt syndrome (THS). Renal biopsy showed a pattern compatible with
      fibrillary glomerulonephritis. For this reason steroid therapy was initiated at a
      dose of 1 mg/kg/day and adjusted according to the clinical course. Neurological
      symptoms regressed shortly after the beginning of therapy and renal function and
      proteinuria remained stable for the 3 years following the withdrawal of steroid
      therapy. Percutaneous renal biopsy was again performed and confirmed the previous
      diagnosis of FibGN in association with other glomerular-lesion-like mesangial
      widening, thickening of capillary walls and severe arterio-arteriolosclerosis.
      This case report describes what is believed to first report of the association of
      FibGN and THS, which both responded to steroid therapy.

PMID- 19181640
TI  - Terminal digit preference: beware of Benford's law.

PMID- 19181641
TI  - Erectile dysfunction and the "window of curability": a harbinger of
      cardiovascular events.

PMID- 19181642
TI  - Targeting the pathogenic role of interleukin 1{beta} in the progression of
      smoldering/indolent myeloma to active disease.

PMID- 19181643
TI  - A population-based, longitudinal study of erectile dysfunction and future
      coronary artery disease.
AB  - OBJECTIVE: To assess the association between erectile dysfunction (ED) and the
      long-term risk of coronary artery disease (CAD) and the role of age as a modifier
      of this association. PARTICIPANTS AND METHODS: From January 1, 1996, to December
      31, 2005, we biennially screened a random sample of 1402 community-dwelling men
      with regular sexual partners and without known CAD for the presence of ED.
      Incidence densities of CAD were calculated after age stratification and adjusted
      for potential confounders by time-dependent Cox proportional hazards models.
      RESULTS: The prevalence of ED was 2% for men aged 40 to 49 years, 6% for men aged
      50 to 59 years, 17% for men aged 60 to 69 years, and 39% for men aged 70 years or
      older. The CAD incidence densities per 1000 person-years for men without ED in
      each age group were 0.94 (40-49 years), 5.09 (50-59 years), 10.72 (60-69 years),
      and 23.30 (> or =70 years). For men with ED, the incidence densities of CAD for
      each age group were 48.52 (40-49 years), 27.15 (50-59 years), 23.97 (60-69
      years), and 29.63 (> or =70 years). CONCLUSION: ED and CAD may be differing
      manifestations of a common underlying vascular pathology. When ED occurs in a
      younger man, it is associated with a marked increase in the risk of future
      cardiac events, whereas in older men, ED appears to be of little prognostic
      importance. Young men with ED may be ideal candidates for cardiovascular risk
      factor screening and medical intervention.

PMID- 19181644
TI  - Induction of a chronic disease state in patients with smoldering or indolent
      multiple myeloma by targeting interleukin 1{beta}-induced interleukin 6
      production and the myeloma proliferative component.
AB  - OBJECTIVE: To conduct in vitro studies as well as a phase 2 clinical trial in
      patients with smoldering or indolent multiple myeloma to determine if interleukin
      1 (IL-1) inhibitors can delay or prevent active myeloma. PATIENTS AND METHODS:
      Stromal cells were cocultured with IL-1beta-expressing myeloma cells in the
      presence of dexamethasone, IL-1 receptor antagonist (IL-1Ra), or both. Levels of
      interleukin 6 (IL-6) and of apoptosis were also quantified. Between November 19,
      2002, and May 24, 2007, 47 patients were enrolled in the study and subsequently
      treated with IL-1Ra. In 25 (53%) of the 47 study patients, low-dose dexamethasone
      (20 mg/wk) was added. The primary end point was progression-free survival (PFS).
      RESULTS: In vitro, IL-1Ra was superior to dexamethasone at inhibiting IL-6
      production; maximal IL-6 inhibition and apoptosis induction were achieved by
      addition of both IL-1Ra and dexamethasone. In the clinical trial, 3 patients
      achieved a minor response to IL-1Ra alone; 5 patients achieved a partial response
      and 4 patients a minor response after addition of dexamethasone. Seven patients
      showed a decrease in the plasma cell labeling index that paralleled a decrease in
      high-sensitivity C-reactive protein (hs-CRP) levels. The median overall PFS was
      37.5 months. The median PFS for patients without (n=12) or with (n=35) a greater
      than 15% decrease in 6-month vs baseline hs-CRP levels was 6 months and more than
      3 years, respectively (P=.002). Disease stability was maintained in 8 patients
      who received therapy for more than 4 years. CONCLUSION: In patients with
      smoldering or indolent multiple myeloma who were at risk of progression to active
      myeloma, treatment with IL-1 inhibitors decreased the myeloma proliferative rate
      and hs-CRP levels in those who responded, leading to a chronic disease state and
      an improved PFS. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00635154.

PMID- 19181645
TI  - Bronchopulmonary actinomycosis associated with hiatal hernia.
AB  - OBJECTIVES: To describe clinicoradiologic and histopathologic features of
      bronchopulmonary actinomycosis and to determine whether hiatal hernia (HH) is a
      potential predisposing factor for bronchopulmonary actinomycosis. PATIENTS AND
      METHODS: We reviewed the medical charts of 10 patients who had bronchopulmonary
      actinomycosis between November 1, 2002, and January 31, 2008. Complete clinical
      data, radiologic studies (chest radiographs and computed tomographic scans), and
      histopathologic features were assessed to investigate clinical manifestations and
      predisposing factors related to bronchopulmonary actinomycosis. RESULTS: The
      series consisted of 6 men and 4 women, with a mean age of 63.5 years; 8 of the
      patients were smokers. Cough and fever were the most common symptoms. Chest
      imaging showed mass-like consolidation in 4 patients, bronchial thickening or
      lung atelectasis with pleural thickening in 2 patients each, and perihilar
      irregular mass or multiple bilateral nodules in 1 patient each. Primary or
      metastatic lung cancer was suspected clinically in 8 of the 10 patients. Foreign
      body-related endobronchial actinomycosis was diagnosed in 6 patients, 5 of whom
      had HH; only 1 had gastroesophageal reflux-related symptoms. Because of bronchial
      obstruction, rigid bronchoscopy was performed in 3 patients, lobectomy in 2, and
      atypical resection in 1. Antibiotic therapy with amoxicillin was given to all
      patients, with resolution of actinomycosis. CONCLUSION: Bronchopulmonary
      actinomycosis is a rare condition that mimics pulmonary malignancy on clinical
      and radiologic grounds. Diagnosis relies on an accurate patient history and
      histopathologic examination. Although further confirmation is required,
      esophageal HH appears to be a potential predisposing factor.

PMID- 19181646
TI  - Pleural fluid characteristics of chylothorax.
AB  - OBJECTIVE: To determine the biochemical parameters of chylous pleural fluids and
      better inform current clinical practice in the diagnosis of chylothorax. PATIENTS
      AND METHODS: We retrospectively reviewed 74 patients with chylothorax (defined by
      the presence of chylomicrons) who underwent evaluation during a 10-year period
      from January 1, 1997, through December 31, 2006. The biochemical parameters and
      appearance of the fluid assessed during diagnostic evaluation were analyzed.
      RESULTS: The study consisted of 37 men (50%) and 37 women (50%), with a median
      age of 61.5 years (range, 20-93 years). Chylothorax was caused by surgical
      procedures in 51%. The chylous pleural fluid appeared milky in only 44%. Pleural
      effusion was exudative in 64 patients (86%) and transudative in 10 patients
      (14%). However, pleural fluid protein and lactate dehydrogenase levels varied
      widely. Transudative chylothorax was present in all 4 patients with cirrhosis but
      was also seen with other causes. The mean +/- SD triglyceride level was 728+/-797
      mg/dL, and the mean +/- SD cholesterol value was 66+/-30 mg/dL. The pleural fluid
      triglyceride value was less than 110 mg/dL in 10 patients (14%) with chylothorax,
      2 of whom had a triglyceride value lower than 50 mg/dL. CONCLUSION: Chylothoraces
      may present with variable pleural fluid appearance and biochemical
      characteristics. Nonmilky appearance is common. Chylous effusions can be
      transudative, most commonly in patients with cirrhosis. Traditional triglyceride
      cutoff values used in excluding the presence of chylothorax may miss the
      diagnosis in fasting patients, particularly in the postoperative state.

PMID- 19181647
TI  - Clinical and genetic description of a family with a high prevalence of autosomal
      dominant restless legs syndrome.
AB  - OBJECTIVE: To conduct clinical and molecular genetic analyses of the members of
      an extended family in Central Indiana with a high prevalence of restless legs
      syndrome (RLS). PARTICIPANTS AND METHODS: From February 1, 2006, through August
      31, 2008, we collected data from members of this family, which is of English
      descent. Genealogical methods were used to expand the family tree, and family
      members were screened with an RLS questionnaire. Telephone interviews and
      personal examinations were performed at Mayo Clinic and during a field trip to
      Central Indiana. Blood samples were collected for molecular genetic analysis. A
      follow-up telephone interview was conducted 1 year later. RESULTS: The family
      tree spans 7 generations with 88 living members, 30 of whom meet the criteria for
      diagnosis of RLS established by the International Restless Legs Syndrome Study
      Group. Three affected family members also have Parkinson disease or essential
      tremor. The mode of RLS inheritance is compatible with an autosomal dominant
      pattern. The affected family members do not exhibit linkage to the 5 known RLS
      loci or mutations in the RLS susceptibility genes MEIS1 and BTBD9. CONCLUSION: Of
      88 members of this single extended family in Central Indiana, 30 were diagnosed
      as having RLS. Because our analysis shows that the disease is not linked to any
      of the known RLS loci or risk-associated genes, we postulate that members of this
      family may carry a gene mutation in a novel genetic locus.

PMID- 19181648
TI  - Erectile dysfunction and cardiovascular disease: efficacy and safety of
      phosphodiesterase type 5 inhibitors in men with both conditions.
AB  - Risk factors for cardiovascular disease and erectile dysfunction (ED) are
      similar, as might be expected given their shared etiologic and pathophysiologic
      origins. It is now generally accepted that most cases of ED result from a
      vascular disturbance of the endothelium. Recent epidemiological studies have
      documented a strong association between ED and comorbid conditions such as
      hypertension, diabetes mellitus, and dyslipidemia. Phosphodiesterase type 5
      (PDE5) inhibitors are recommended as first-line therapy for erection problems of
      all etiologies and severities. The efficacy and safety of PDE5 inhibitors in the
      general ED population is well documented and has been extensively reviewed. To
      examine the association between ED and vascular disorders in the context of
      current knowledge regarding PDE5 inhibitors, an electronic search was performed
      of articles published from January 2002 through April 2008 using the PubMed,
      EMBASE, and MEDLINE databases. Although preference was given to randomized,
      blinded, controlled clinical trials, data from retrospective studies were also
      reviewed when appropriate. This analysis revealed that the clinical evidence
      linking ED to future cardiovascular events is compelling, presenting physicians
      with a unique interventional opportunity to address underlying cardiovascular
      health concerns in men presenting with ED. In most studies, PDE5 inhibitors were
      shown to effectively and safely improve erectile function regardless of cause,
      severity, or presence of comorbid conditions, including hypertension, diabetes
      mellitus, and dyslipidemia.

PMID- 19181649
TI  - Expanding the recognition and assessment of bleeding events associated with
      antiplatelet therapy in primary care.
AB  - Antiplatelet therapy is an evidence-based, guideline-recommended, worldwide
      standard of care for treatment of patients with atherothrombosis. However,
      clinical implementation of the guidelines is suboptimal, in part because of
      physician and patient nonadherence. The increased risk of bleeding associated
      with antiplatelet therapy is often the reason for nonadherence, and several
      programs have been created to increase adherence to guideline treatment
      recommendations. Despite the relative success of such initiatives, including Can
      Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes
      With Early Implementation of the ACC/AHA Guidelines, Guidelines Applied in
      Practice, and the American Heart Association's Get With the Guidelines and a
      Science Advisory, a current estimate is that less than 50% of atherothrombotic
      patients are taking antiplatelet therapies as recommended by national guidelines.
      A PubMed and MEDLINE search of the literature (January 1, 1983-May 15, 2008) was
      performed to examine the bleeding risks associated with various antiplatelet
      therapies. Relevant clinical trials, observational registry data, and other
      studies relevant to treatment and guideline recommendations were selected from
      articles generated through specific search terms. This comprehensive review
      contributes to the understanding of the benefit-to-risk ratio of antiplatelet
      therapy for patients with atherothrombosis.

PMID- 19181650
TI  - Suboptimal response to or failure of imatinib treatment for chronic myeloid
      leukemia: what is the optimal strategy?
AB  - Treatment responses to imatinib vary among patients with chronic myeloid leukemia
      (CML), and definitions of treatment failure and suboptimal response have been
      published. This article discusses monitoring and treatment of patients with CML
      after failure of or suboptimal response to imatinib therapy. We reviewed articles
      listed on PubMed from January 1, 2002, to July 31, 2008, and abstracts from the
      2007 Annual Meeting of the American Society of Hematology. Search terms used were
      chronic myeloid/myelogenous leukemia, imatinib, and BCR-ABL. To enable early
      recognition of suboptimal responses, patients should be frequently monitored
      according to published guidelines, including cytogenetic analysis every 6 months
      until a complete response is achieved and molecular monitoring every 3 months
      from the start of therapy or monthly if an increasing BCR-ABL1 transcript level
      is detected. Mutational analysis of BCR-ABL1 may assist with treatment selection.
      A recent survey suggests that a notable proportion of physicians do not follow
      treatment guidelines and that broader communication is required. Recent
      recommendations state that, in patients whose response to imatinib at 400 mg/d is
      suboptimal, the dose should be increased, whereas alternative therapies, such as
      dasatinib, nilotinib, and allogeneic stem cell transplant (in eligible patients),
      and imatinib dose escalation should be considered after imatinib failure.
      However, clinical data are lacking to confirm this sequence of treatments, and
      introducing alternative therapies at an earlier stage of treatment, for example,
      after a suboptimal response, may produce better long-term outcomes in a higher
      proportion of patients. Patient and disease characteristics should be carefully
      considered to optimize treatment strategy for CML.

PMID- 19181651
TI  - Contrast-induced acute kidney injury: specialty-specific protocols for
      interventional radiology, diagnostic computed tomography radiology, and
      interventional cardiology.
AB  - Contrast-induced acute kidney injury (AKI) (also known as contrast-induced
      nephropathy) is an abrupt deterioration in renal function that can be associated
      with use of iodinated contrast medium. Although the increase in serum creatinine
      concentration is transient in most cases, contrast-induced AKI may lead to
      increased morbidity and mortality rates in selected at-risk populations. This
      review summarizes the findings of a multidisciplinary panel composed of computed
      tomography radiologists, interventional radiologists, cardiologists, and
      nephrologists convened to address the specialty-specific issues associated with
      minimizing the incidence of contrast-induced AKI. As part of this initiative, the
      panel developed specialty-specific protocols for preventing contrast-induced AKI,
      taking into account, for example, the variations in patient risk profile,
      inpatient or outpatient status, and staffing resources that characterize various
      clinical settings. The 3 protocols, each reflecting a consensus of expert
      opinion, address the prevention of contrast-induced AKI in interventional
      radiology, diagnostic computed tomography radiology, and interventional
      cardiology settings. The protocols are presented in the context of a review of
      recent guidelines and published reports of trials that discuss contrast-induced
      AKI and its prevention. The panel reviewed materials retrieved by a PubMed search
      covering the period January 1990 through January 2008 and used combinations of
      key words associated with the prevention and treatment of contrast-induced AKI.
      In addition, the panel reviewed the reference lists of selected articles and the
      tables of contents posted on the Web sites of selected journals for relevant
      publications not retrieved in the PubMed searches.

PMID- 19181652
TI  - The top 10 things nephrologists wish every primary care physician knew.
AB  - Renal disease is commonly encountered by primary care physicians during their day
      to-day visits with patients. Common renal disorders include hypertension,
      proteinuria, kidney stones, and chronic kidney disease. Despite their prevalence,
      many physicians may be unfamiliar with the diagnosis and initial treatment of
      these common renal disorders. Early recognition and intervention are important in
      slowing the progression of chronic kidney disease and preventing its
      complications. The evidence-based pearls in this article will help primary care
      physicians avoid common pitfalls in the recognition and treatment of such
      disorders and guide their decision to refer their patients to a specialist.

PMID- 19181653
TI  - 84-year-old woman with hemodialysis-associated shortness of breath.

PMID- 19181655
TI  - Upper extremity deep venous thrombosis after prolonged air travel in a patient
      with a permanent pacemaker.

PMID- 19181654
TI  - Pulmonary hypertension: diagnosis and management.
AB  - Pulmonary arterial hypertension is a progressive, symptomatic, and ultimately
      fatal disorder for which substantial advances in treatment have been made during
      the past decade. Effective management requires timely recognition and accurate
      diagnosis of the disorder and appropriate selection among therapeutic
      alternatives. Despite progress in treatment, obstacles remain that impede the
      achievement of optimal outcomes. The current article provides an overview of the
      pathobiologic mechanisms of pulmonary arterial hypertension, including genetic
      substrates and molecular and cellular mechanisms, and describes the clinical
      manifestations and classification of pulmonary arterial hypertension. The article
      also reviews established approaches to evaluation and treatment, with emphasis on
      the appropriate application of calcium channel blockers, prostacyclin analogues,
      endothelin receptor antagonists, and phosphodiesterase 5 inhibitors. In addition,
      the authors discuss unresolved issues that may complicate patient management,
      such as the clinical importance of mild or exercise-related pulmonary arterial
      hypertension, and they identify avenues by which treatment may advance in the
      future through the use of combination treatment, outcomes assessment, and
      exploration of alternative pharmacologic strategies.

PMID- 19181656
TI  - Circulating neutrophil gelatinase-associated lipocalin: a useful biomarker for
      assessing disease activity of ANCA-associated vasculitis.
AB  - OBJECTIVES: Biomarkers for assessing disease activity of patients with anti
      neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) are
      important in identifying relapse and guiding treatment. ANCA-induced neutrophil
      activation and degranulation played an important role in the pathogenesis of AAV
      and neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of
      neutrophil degranulation. The purpose of the current study is to investigate
      whether NGAL is a useful biomarker for assessing disease activity of patients
      with AAV. METHODS: Sequential sera from 19 patients with AAV at initial onset,
      remission and relapse were collected. Serum NGAL was detected using commercial
      ELISA kits. The association between serum NGAL and the Birmingham Vasculitis
      Activity Score (BVAS), ESR, CRP as well as serum ANCA was further investigated.
      RESULTS: The 19 patients had 19 relapses. The levels of serum NGAL in patients at
      initial onset and relapse were both significantly higher than that at remission
      (285.5 +/- 65.5 ng/ml vs 96.7 +/- 22.2 ng/ml, P < 0.05; 430.3 +/- 98.7 ng/ml vs
      96.7 +/- 22.2 ng/ml, P < 0.05, respectively). It was still the case after
      adjusting for renal function. The levels of serum NGAL closely correlated with
      BVAS as well as the level of ESR, CRP and ANCA. Moreover, serum NGAL level had a
      closer correlation with BVAS than ESR, CRP and ANCA did. CONCLUSION: Circulating
      NGAL could be used as a useful biomarker for assessing disease activity of
      patients with AAV.

PMID- 19181657
TI  - Establishment and partial validation of a patient skin self-assessment
      questionnaire in systemic sclerosis.
AB  - OBJECTIVES: To construct a patient self-assessment questionnaire testing whether
      patients can provide valid information about their skin thickness, tethering and
      thinness. METHODS: The questionnaire contained questions about the 17 body areas
      identical to those investigated in the Modified Rodnan Skin Score (MRSS). The
      baseline and 1 yr follow-up values of thickening, tethering and thinning were
      scored on a scale of 0-3, by 131 consecutive patients. RESULTS: The questionnaire
      was feasible. The test-retest reliability was good, with an intraclass
      correlation coefficient of 0.5-0.6. The MRSS correlated with the 17-area
      thickness score (rho = 0.435, P < 0.001). Both the patient-reported thickness and
      tethering scores and the expert-measured MRSS and tethering scores correlated
      highly with each other (rho = 0.523, P < 0.001 and rho = 0.637, P < 0.001,
      respectively). The patient-reported thinness scores did not show any correlation
      with the examiner-measured skin thickening/tethering. All thickness-related
      scores were sorted into the same factor by principal component analysis.
      Conversely, skin thinness scores were sorted into a distinct factor. Skin
      thickness scores reported by diffuse SSc patients were different from those of
      the limited SSc cases (P < 0.05). CONCLUSIONS: We validated the skin thickness
      domain of the questionnaire, except the responsiveness. Because of the low mean
      MRSS of patients in this investigation, the patient self-assessment validation
      procedure should be repeated with cases exhibiting more extensive skin
      involvement. Patient-reported and examiner-measured tethering may not be used as
      independent instruments of skin involvement. The skin thinness domain may contain
      valuable independent information, therefore it also merits further investigation.

PMID- 19181658
TI  - Association of killer cell immunoglobulin-like receptors with primary Sjogren's
      syndrome.
AB  - OBJECTIVE: SS is a chronic inflammatory condition characterized by systemic and
      tissue-specific autoimmune features. In view of recent findings indicating a role
      for killer cell immunoglobulin-like receptors (KIRs) in the pathogenesis of other
      autoimmune rheumatic disorders such as SSc, and the autoimmune disorders RA and
      PsA, we sought to determine whether KIRs predict general or specific
      susceptibility in SS. METHODS: Eleven separate KIR genes were typed using PCR
      sequence-specific primers on genomic DNA from 72 patients diagnosed with primary
      SS and a control panel consisting of 223 blood donors. RESULTS: We found no
      individual KIR genes to be associated with SS. In contrast, 11 patients with
      primary SS (15%) and 9 control blood donors (4%) had KIR genotypes with the
      activating KIR2DS2 in the absence of its corresponding inhibitory homologue
      KIR2DL2 (P = 0.01). Further analysis of these individuals showed that seven SS
      patients were positive for HLA-C ligand for KIR2DS2 only compared with one
      control sample (P = 0.00026). CONCLUSION: The genetic combination of KIR2DS2+ and
      KIR2DL2- in the presence of HLA-C ligand specific for activating KIR2DS2 is
      associated with primary SS. This implies that autologous KIR-ligand interaction
      is a contributory factor to predisposition for this disease.

PMID- 19181659
TI  - The organelle proteome of the DT40 lymphocyte cell line.
AB  - A major challenge in eukaryotic cell biology is to understand the roles of
      individual proteins and the subcellular compartments in which they reside. Here,
      we use the localization of organelle proteins by isotope tagging technique to
      complete the first proteomic analysis of the major organelles of the DT40
      lymphocyte cell line. This cell line is emerging as an important research tool
      because of the ease with which gene knockouts can be generated. We identify 1090
      proteins through the analysis of preparations enriched for integral membrane or
      soluble and peripherally associated proteins and localize 223 proteins to the
      endoplasmic reticulum, Golgi, lysosome, mitochondrion, or plasma membrane by
      matching their density gradient distributions to those of known organelle
      residents. A striking finding is that within the secretory and endocytic pathway
      a high proportion of proteins are not uniquely localized to a single organelle,
      emphasizing the dynamic steady-state nature of intracellular compartments in
      eukaryotic cells.

PMID- 19181661
TI  - Accurate dose assessment system for an exposed person utilising radiation
      transport calculation codes in emergency response to a radiological accident.
AB  - A system has been developed to assess radiation dose distribution inside the body
      of exposed persons in a radiological accident by utilising radiation transport
      calculation codes-MCNP and MCNPX. The system consists mainly of two parts, pre
      processor and post-processor of the radiation transport calculation. Programs for
      the pre-processor are used to set up a 'problem-dependent' input file, which
      defines the accident condition and dosimetric quantities to be estimated. The
      program developed for the post-processor part can effectively indicate dose
      information based upon the output file of the code. All of the programs in the
      dosimetry system can be executed with a generally used personal computer and
      accurately give the dose profile to an exposed person in a radiological accident
      without complicated procedures. An experiment using a physical phantom was
      carried out to verify the availability of the dosimetry system with the developed
      programs in a gamma ray irradiation field.

PMID- 19181660
TI  - Statistical model to analyze quantitative proteomics data obtained by 18O/16O
      labeling and linear ion trap mass spectrometry: application to the study of
      vascular endothelial growth factor-induced angiogenesis in endothelial cells.
AB  - Statistical models for the analysis of protein expression changes by stable
      isotope labeling are still poorly developed, particularly for data obtained by
      16O/18O labeling. Besides large scale test experiments to validate the null
      hypothesis are lacking. Although the study of mechanisms underlying biological
      actions promoted by vascular endothelial growth factor (VEGF) on endothelial
      cells is of considerable interest, quantitative proteomics studies on this
      subject are scarce and have been performed after exposing cells to the factor for
      long periods of time. In this work we present the largest quantitative proteomics
      study to date on the short term effects of VEGF on human umbilical vein
      endothelial cells by 18O/16O labeling. Current statistical models based on
      normality and variance homogeneity were found unsuitable to describe the null
      hypothesis in a large scale test experiment performed on these cells, producing
      false expression changes. A random effects model was developed including four
      different sources of variance at the spectrum-fitting, scan, peptide, and protein
      levels. With the new model the number of outliers at scan and peptide levels was
      negligible in three large scale experiments, and only one false protein
      expression change was observed in the test experiment among more than 1000
      proteins. The new model allowed the detection of significant protein expression
      changes upon VEGF stimulation for 4 and 8 h. The consistency of the changes
      observed at 4 h was confirmed by a replica at a smaller scale and further
      validated by Western blot analysis of some proteins. Most of the observed changes
      have not been described previously and are consistent with a pattern of protein
      expression that dynamically changes over time following the evolution of the
      angiogenic response. With this statistical model the 18O labeling approach
      emerges as a very promising and robust alternative to perform quantitative
      proteomics studies at a depth of several thousand proteins.

PMID- 19181662
TI  - Differential Processing of {alpha}- and {beta}-Defensin Precursors by Matrix
      Metalloproteinase-7 (MMP-7).
AB  - Proteolytic processing of defensins is a critical mode of posttranslational
      regulation of peptide activity. Because mouse alpha-defensin precursors are
      cleaved and activated by matrix metalloproteinase-7 (MMP-7), we determined if
      additional defensin molecules, namely human neutrophil defensin pro-HNP-1 and
      beta-defensins, are targets for MMP-7. We found that MMP-7 cleaves within the pro
      domain of the HNP-1 precursor, a reaction that does not generate the mature
      peptide but produces a 59-amino acid intermediate. This intermediate, which
      retains the carboxyl-terminal end of the pro-domain, had antimicrobial activity,
      indicating that the residues important for masking defensin activity reside in
      the amino terminus of this domain. Mature HNP-1 was resistant to processing by
      MMP-7 unless the peptide was reduced and alkylated, demonstrating that only the
      pro-domain of alpha-defensins is normally accessible for cleavage by this enzyme.
      From the 47-residue HBD-1 precursor, MMP-7 catalyzed removal of 6 amino acids
      from the amino terminus. Neither a 39-residue intermediate form of HBD-1 nor the
      mature 36-residue form of HBD-1 was cleaved by MMP-7. In addition, both pro-HBD
      2, with its shorter amino-terminal extension, and pro-HBD-3 were resistant to MMP
      7. However, human and mouse beta-defensin precursors that lack disulfide bonding
      contain a cryptic MMP-7-sensitive site within the mature peptide moiety. These
      findings support and extend accumulating evidence that the native three
      dimensional structure of both alpha- and beta-defensins protects the mature
      peptides against proteolytic processing by MMP-7. We also conclude that sites for
      MMP-7 cleavage are more common at the amino termini of alpha-defensin rather than
      beta-defensin precursors, and that catalysis at these sites in alpha-defensin pro
      domains results in acquisition of defensin activity.

PMID- 19181663
TI  - Cold adaptation of zinc metalloproteases in the thermolysin family from deep sea
      and arctic sea ice bacteria revealed by catalytic and structural properties and
      molecular dynamics: new insights into relationship between conformational
      flexibility and hydrogen bonding.
AB  - Increased conformational flexibility is the prevailing explanation for the high
      catalytic efficiency of cold-adapted enzymes at low temperatures. However, less
      is known about the structural determinants of flexibility. We reported two novel
      cold-adapted zinc metalloproteases in the thermolysin family, vibriolysin MCP-02
      from a deep sea bacterium and vibriolysin E495 from an Arctic sea ice bacterium,
      and compared them with their mesophilic homolog, pseudolysin from a terrestrial
      bacterium. Their catalytic efficiencies, k(cat)/K(m) (10-40 degrees C), followed
      the order pseudolysin < MCP-02 < E495 with a ratio of approximately 1:2:4. MCP-02
      and E495 have the same optimal temperature (T(opt), 57 degrees C, 5 degrees C
      lower than pseudolysin) and apparent melting temperature (T(m) = 64 degrees C,
      approximately 10 degrees C lower than pseudolysin). Structural analysis showed
      that the slightly lower stabilities resulted from a decrease in the number of
      salt bridges. Fluorescence quenching experiments and molecular dynamics
      simulations showed that the flexibilities of the proteins were pseudolysin < MCP
      02 < E495, suggesting that optimization of flexibility is a strategy for cold
      adaptation. Molecular dynamics results showed that the ordinal increase in
      flexibility from pseudolysin to MCP-02 and E495, especially the increase from MCP
      02 to E495, mainly resulted from the decrease of hydrogen-bond stability in the
      dynamic structure, which was due to the increase in asparagine, serine, and
      threonine residues. Finally, a model for the cold adaptation of MCP-02 and E495
      was proposed. This is the first report of the optimization of hydrogen-bonding
      dynamics as a strategy for cold adaptation and provides new insights into the
      structural basis underlying conformational flexibility.

PMID- 19181664
TI  - Distinct transport and intracellular activities of two GlcAT-P isoforms.
AB  - A neural glycotope, human natural killer-1 carbohydrate, is involved in synaptic
      plasticity. The key biosynthetic enzyme is a glucuronyltransferase, GlcAT-P, a
      type II membrane protein comprising an N-terminal cytoplasmic tail, transmembrane
      domain, stem region, and C-terminal catalytic domain. Previously, we reported
      that GlcAT-P has two isoforms differing in only the presence or absence of the N
      terminal 13 amino acids (P-N13) in the cytoplasmic tail, but the functional
      distinction of these two isoforms has not been reported. Herein, we show that
      when expressed in Neuro2A cells, short form GlcAT-P (sGlcAT-P) exhibited
      significantly higher glucuronylation activity than the longer form (lGlcAT-P),
      despite their comparable specific activities in vitro. In addition, sGlcAT-P was
      strictly localized in Golgi apparatus, whereas lGlcAT-P was mainly localized in
      Golgi but partly in the endoplasmic reticulum. We demonstrated that the small
      GTPase, Sar1, recognized a dibasic motif in the cytoplasmic tail near P-N13 that
      was important for exiting the endoplasmic reticulum, and Sar1 interacted with
      sGlcAT-P more strongly than lGlcAT-P. Finally, the attachment of P-N13 to another
      glycosyltransferase, polysialyltransferase-I (ST8Sia-IV), had similar effects,
      such as reduced activity and entrapment within endoplasmic reticulum. These
      results suggest that P-N13 can control glycosyltransferase transport through Sar1
      binding interference.

PMID- 19181665
TI  - Poly(ADP-ribose) Polymerase 1 Interacts with Nuclear Respiratory Factor 1 (NRF-1)
      and Plays a Role in NRF-1 Transcriptional Regulation.
AB  - Nuclear respiratory factor 1 (NRF-1) is one of the key transcriptional activators
      for nuclear-coded genes involved in mitochondrial biogenesis and function as well
      as for many housekeeping genes. A transcriptional co-activator PGC-1 and its
      related family member PRC have previously been shown to interact with NRF-1 and
      co-activate NRF-1. We show here that NRF-1 can also directly interact with
      poly(ADP-ribose) polymerase 1 (PARP-1) and co-purify the PARP-1.DNA
      PK.Ku80.Ku70.topoisomerase IIbeta-containing protein complex. Our in vitro
      binding experiments show that DNA-binding/dimerization domain of NRF-1 and the N
      terminal half of PARP-1, which contains two Zinc fingers and the auto
      modification domain, are responsible for the interaction, and that this
      interaction occurs with or without PARP-1 poly(ADP-ribosyl)ation (PARylation).
      DNA-bound NRF-1 can form a complex with PARP-1, suggesting that NRF-1 can recruit
      the PARP-1.DNA-PK.Ku80.Ku70.topoisomerase IIbeta-containing protein complex to
      the promoter. PARP-1 can also PARylate the DNA-binding domain of NRF-1 and
      negatively regulate NRF-1.PARP-1 interaction. Transient transfection and
      chromatin immunoprecipitation experiments suggest that PARP-1 plays a role during
      transcriptional activation by NRF-1. Our finding identifies a new aspect of
      transcriptional regulation used by NRF-1.

PMID- 19181666
TI  - An NMR study of the interaction of the N-terminal cytoplasmic tail of the Wilson
      disease protein with copper(I)-HAH1.
AB  - ATP7B is a human P(1B)-type ATPase that has a crucial role in maintaining
      copper(I) homeostasis. Mutations in the corresponding gene are the cause of
      Wilson disease. Among its various distinguishing features is a long (
      approximately 630 amino acids) N-terminal cytosolic tail containing six domains
      that are individually folded and capable of binding one copper(I) ion each. We
      expressed the entire tail as a single construct in Escherichia coli and
      investigated its interaction with its copper chaperone (i.e. HAH1) by solution
      NMR spectroscopy. We observed that all six of the metal-binding domains were
      metallated by Cu(I)-HAH1, with the first, the second, and the fourth domains
      forming an adduct with it. This behavior is different from that of the highly
      similar human ATPase ATP7A, in which only two domains form such an adduct. The
      distinct behaviors of the different domains were analyzed in terms of the
      energetics of Cu(I) transfer, hinting at a specific role of the interaction with
      copper(I)-HAH1 in the overall functional process.

PMID- 19181667
TI  - Streptococcus pneumoniae endohexosaminidase D, structural and mechanistic insight
      into substrate-assisted catalysis in family 85 glycoside hydrolases.
AB  - Endo-beta-d-glucosaminidases from family 85 of glycoside hydrolases (GH85
      endohexosaminidases) act to cleave the glycosidic linkage between the two N
      acetylglucosamine units that make up the chitobiose core of N-glycans.
      Endohexosaminidase D (Endo-D), produced by Streptococcus pneumoniae, is believed
      to contribute to the virulence of this organism by playing a role in the
      deglycosylation of IgG antibodies. Endohexosaminidases have received significant
      attention for this reason and, moreover, because they are powerful tools for
      chemoenzymatic synthesis of proteins having defined glycoforms. Here we describe
      mechanistic and structural studies of the catalytic domain (SpGH85) of Endo-D
      that provide compelling support for GH85 enzymes using a catalytic mechanism
      involving substrate-assisted catalysis. Furthermore, the structure of SpGH85 in
      complex with the mechanism-based competitive inhibitor NAG-thiazoline (K(d) = 28
      microm) provides a coherent rationale for previous mutagenesis studies of Endo-D
      and other related GH85 enzymes. We also find GH85, GH56, and GH18 enzymes have a
      similar configuration of catalytic residues. Notably, GH85 enzymes have an
      asparagine in place of the aspartate residue found in these other families of
      glycosidases. We propose that this residue, as the imidic acid tautomer, acts
      analogously to the key catalytic aspartate of GH56 and GH18 enzymes. This
      topographically conserved arrangement of the asparagine residue and a conserved
      glutamic acid, coupled with previous kinetic studies, suggests these enzymes may
      use an unusual proton shuttle to coordinate effective general acid and base
      catalysis to aid cleavage of the glycosidic bond. These results collectively
      provide a blueprint that may be used to facilitate protein engineering of these
      enzymes to improve their function as biocatalysts for synthesizing glycoproteins
      having defined glycoforms and also may serve as a guide for generating inhibitors
      of GH85 enzymes.

PMID- 19181668
TI  - Properties of the thioredoxin fold superfamily are modulated by a single amino
      acid residue.
AB  - The ubiquitous thioredoxin fold proteins catalyze oxidation, reduction, or
      disulfide exchange reactions depending on their redox properties. They also play
      vital roles in protein folding, redox control, and disease. Here, we have shown
      that a single residue strongly modifies both the redox properties of thioredoxin
      fold proteins and their ability to interact with substrates. This residue is
      adjacent in three-dimensional space to the characteristic CXXC active site motif
      of thioredoxin fold proteins but distant in sequence. This residue is just N
      terminal to the conservative cis-proline. It is isoleucine 75 in the case of
      thioredoxin. Our findings support the conclusion that a very small percentage of
      the amino acid residues of thioredoxin-related proteins are capable of dictating
      the functions of these proteins.

PMID- 19181669
TI  - Fyn tyrosine kinase regulates the surface expression of
      glycosylphosphatidylinositol-linked ephrin via the modulation of sphingomyelin
      metabolism.
AB  - Glycosylphosphatidylinositol-linked ephrin-As play important roles in various
      biological events, such as neuronal development and immune responses. Because the
      surface amount of ephrin-As is critical in these events, the trafficking of
      ephrin-As must be regulated by intracellular machinery. In particular, Src family
      protein-tyrosine kinases regulate the intracellular trafficking of several
      membrane molecules and act downstream of ephrin-As; whether they affect the
      trafficking of ephrin-As, however, has remained unexplored. Here, we report that
      the activity of Src family protein-tyrosine kinases, particularly Fyn, negatively
      regulates the cell-surface amount of ephrin-As. The expression of constitutively
      active Fyn decreases the surface amount of ephrin-As. Conversely, the expression
      of dominant-negative Fyn or the application of a Src-family inhibitor increases
      the surface amount of ephrin-A2. The total cellular amount of ephrin-A is
      inversely correlated with its amount on the surface, suggesting that ephrin-As
      are more stable in the intracellular compartment. The expression of
      constitutively active Fyn increases the amount of sphingomyelin clusters on the
      plasma membrane, whereas inhibiting Fyn decreases it. Moreover, the inhibition of
      sphingomyelin synthesis greatly increases the surface amount of ephrin-As.
      Altogether, these results suggest that Fyn regulates the surface amount of ephrin
      As by modulating the metabolism of sphingomyelin, which presumably inhibits the
      trafficking of ephrin-As from endosomes to the plasma membrane. The signaling
      cascade described here may function as part of the negative feedback loop of
      ephrin-A function.

PMID- 19181670
TI  - The MPH1 gene of Saccharomyces cerevisiae functions in Okazaki fragment
      processing.
AB  - Saccharomyces cerevisiae MPH1 was first identified as a gene encoding a 3' to 5'
      DNA helicase, which when deleted leads to a mutator phenotype. In this study, we
      isolated MPH1 as a multicopy suppressor of the dna2K1080E helicase-negative
      lethal mutant. Purified Mph1 stimulated the endonuclease activities of both Fen1
      and Dna2, which act faithfully in the processing of Okazaki fragments. This
      stimulation required neither ATP hydrolysis nor the helicase activity of Mph1.
      Multicopy expression of MPH1 also suppressed the temperature-sensitive growth
      defects in cells expressing dna2Delta405N, which lacks the N-terminal 405 amino
      acids of Dna2. However, Mph1 did not stimulate the endonuclease activity of the
      Dna2Delta405N mutant protein. The stimulation of Fen1 by Mph1 was limited to flap
      structured substrates; Mph1 hardly stimulated the 5' to 3' exonuclease activity
      of Fen1. Mph1 binds to flap-structured substrate more efficiently than to nicked
      duplex structures, suggesting that the stimulatory effect of Mph1 is exerted
      through its binding to DNA substrates. In addition, we found that Mph1 reversed
      the inhibitory effects of replication protein A on Fen1 activity. Our biochemical
      and genetic data indicate that the in vivo suppression of Dna2 defects observed
      with both dna2K1080E and dna2Delta405N mutants occur via stimulation of Fen1
      activity. These findings suggest that Mph1 plays an important, although not
      essential, role in processing of Okazaki fragments by facilitating the formation
      of ligatable nicks.

PMID- 19181671
TI  - Defining the potassium binding region in an apple terpene synthase.
AB  - Terpene synthases are a family of enzymes largely responsible for synthesizing
      the vast array of terpenoid compounds known to exist in nature. Formation of
      terpenoids from their respective 10-, 15-, or 20-carbon atom prenyl diphosphate
      precursors is initiated by divalent (M(2+)) metal ion-assisted electrophilic
      attack. In addition to M(2+), monovalent cations (M(+)) have also been shown to
      be essential for the activity of certain terpene synthases most likely by
      facilitating substrate binding or catalysis. An apple alpha-farnesene synthase
      (MdAFS1), which has a dependence upon potassium (K(+)), was used to identify
      active site regions that may be important for M(+) binding. Protein homology
      modeling revealed a surface-exposed loop (H-alphal loop) in MdAFS1 that fulfilled
      the necessary requirements for a K(+) binding region. Site-directed mutagenesis
      analysis of specific residues within this loop then revealed their crucial
      importance to this K(+) response and strongly implicated specific residues in
      direct K(+) binding. The role of the H-alphal loop in terpene synthase K(+)
      coordination was confirmed in a Conifer pinene synthase also using site-directed
      mutagenesis. These findings provide the first direct evidence for a specific M(+)
      binding region in two functionally and phylogenetically divergent terpene
      synthases. They also provide a basis for understanding K(+) activation in other
      terpene synthases and establish a new role for the H-alphal loop region in
      terpene synthase catalysis.

PMID- 19181672
TI  - Clinical, histological and genetic characterization of reducing body myopathy
      caused by mutations in FHL1.
AB  - We recently identified the X-chromosomal four and a half LIM domain gene FHL1 as
      the causative gene for reducing body myopathy, a disorder characterized by
      progressive weakness and intracytoplasmic aggregates in muscle that exert
      reducing activity on menadione nitro-blue-tetrazolium (NBT). The mutations
      detected in FHL1 affected highly conserved zinc coordinating residues within the
      second LIM domain and lead to the formation of aggregates when transfected into
      cells. Our aim was to define the clinical and morphological phenotype of this
      myopathy and to assess the mutational spectrum of FHL1 mutations in reducing body
      myopathy in a larger cohort of patients. Patients were ascertained via the
      detection of reducing bodies in muscle biopsy sections stained with menadione-NBT
      followed by clinical, histological, ultrastructural and molecular genetic
      analysis. A total of 11 patients from nine families were included in this study,
      including seven sporadic patients with early childhood onset disease and four
      familial cases with later onset. Weakness in all patients was progressive,
      sometimes rapidly so. Respiratory failure was common and scoliosis and spinal
      rigidity were significant in some of the patients. Analysis of muscle biopsies
      confirmed the presence of aggregates of FHL1 positive material in all biopsies.
      In two patients in whom sequential biopsies were available the aggregate load in
      muscle sections appeared to increase over time. Ultrastructural analysis revealed
      that cytoplasmic bodies were regularly seen in conjunction with the reducing
      bodies. The mutations detected were exclusive to the second LIM domain of FHL1
      and were found in both sporadic as well as familial cases of reducing body
      myopathy. Six of the nine mutations affected the crucial zinc coordinating
      residue histidine 123. All mutations in this residue were de novo and were
      associated with a severe clinical course, in particular in one male patient
      (H123Q). Mutations in the zinc coordinating residue cysteine 153 were associated
      with a milder phenotype and were seen in the familial cases in which the boys
      were still more severely affected compared to their mothers. We expect the mild
      end of the spectrum to significantly expand in the future. On the severe end of
      the spectrum we define reducing body myopathy as a progressive disease with
      early, but not necessarily congenital onset, distinguishing this condition from
      the classic essentially non-progressive congenital myopathies.

PMID- 19181673
TI  - The effect of interrupted 5-day training on Integrated Management of Neonatal and
      Childhood Illness on the knowledge and skills of primary health care workers.
AB  - The conventional 8-day Integrated Management of Neonatal and Childhood Illness
      (IMNCI) training package poses several operational constraints, particularly due
      to its long duration. A 5-day training package was developed and administered in
      an interrupted mode of 3 days and 2 days duration with a break of 4 days in
      between, in a district of Haryana state in northern India. Improvement in the
      knowledge and skills of 50 primary health care workers following the interrupted
      5-day training was compared with that of 35 primary health care workers after the
      conventional 8-day IMNCI training package. The average score increased
      significantly (P < 0.05) from 46.3 to 74.6 in 8-day training and from 40.0 to
      73.2 in 5-day training. Knowledge score improved for all health conditions, like
      anaemia, diarrhoea, immunization, malnutrition, malaria, meningitis and possible
      severe bacterial infection, and for breastfeeding in 8-day as well as in 5-day
      training. Average skills score for respiratory problems increased from 38 to 57
      in 8-day training and from 41 to 91 in 5-day training. Corresponding increases in
      skill scores for diarrhoea assessment were from 28 to 67 and 48 to 75, and for
      breastfeeding assessment from 33 to 84 and 42 to 86 in 8-day and 5-day training,
      respectively. Average counselling skill score also rose from 42 to 89 in 8-day
      and from 37 to 70 in 5-day training. A direct cost saving of US$813 for a batch
      of 25 trainees and an indirect cost saving of 3 days per trainee and resource
      person makes the interrupted 5-day IMNCI training more cost-effective.

PMID- 19181674
TI  - Paying for hospital-based care of Kala-azar in Nepal: assessing catastrophic,
      impoverishment and economic consequences.
AB  - Households obtaining health care services in developing countries incur
      substantial costs, despite services generally being provided free of charge by
      public health institutions. This constitutes an economic burden on low-income
      households, and contributes to deepening their level of poverty. In addition to
      the economic burden of obtaining health care, the method of financing these
      payments has implications for the distribution of household assets. This effect
      on resource-poor households is amplified since they have decreased access to
      health insurance. Recent literature, however, ignores the importance of the
      method of financing health care payments. This paper looks at the case of Nepal
      and highlights the impact on households of paying for hospital-based care of Kala
      azar (KA) by analysing the catastrophic, impoverishment and economic consequences
      of their coping strategies. The paper utilizes micro-data on a random selection
      of 50% of the KA-affected households of Siraha and Saptari districts of Nepal.
      The empirical results suggest that direct costs of hospital-based treatment of KA
      are catastrophic since they consume 17% of annual household income. This
      expenditure causes more than 20% of KA-affected households to fall below the
      poverty line, with the remaining households being pushed into the category of
      marginal poor; the poverty gap ratio is more than 90%. Further, KA incidence can
      have prolonged and severe economic consequences for the household economy due to
      the mechanisms of informal sector financing to which households resort. A heavy
      burden of loan repayments can lead households on a downward spiral that
      eventually becomes a poverty trap. In other words, the method of financing health
      care payments is an important ingredient in understanding the economic burden of
      disease.

PMID- 19181675
TI  - The public sector's role in infertility management in India.
AB  - This objective of this paper is to explore the public sector's role in
      infertility management in India. It focuses on services available in the public
      sector, problems faced by and critiques of public sector providers. A postal
      survey was conducted with a sample of 6000 gynaecologists and in-depth interviews
      were conducted with 39 gynaecologists in four cities. The role of the public
      sector in infertility management is weak as even basic investigations and
      services were limited or incomplete. Inadequate infrastructure, inappropriate
      management including time management, lack of information and training, absence
      of clear protocols at all levels, private practice by public health doctors, pre
      occupation with other health issues and lack of regulation were the main problems
      mentioned by providers. Amongst key recommendations are realistic and low-cost
      management, streamlining and regulating services, counselling of couples,
      providing information and raising awareness of patients, health personnel and
      policy makers.

PMID- 19181676
TI  - Invited commentary.

PMID- 19181677
TI  - Invited commentary.

PMID- 19181678
TI  - Large replication study and meta-analyses of DVWA as an osteoarthritis
      susceptibility locus in European and Asian populations.
AB  - Recently, through a genome wide association study in Japanese knee osteoarthritis
      (OA) cases, a previously unknown gene, DVWA, was identified. The non-synonymous
      single nucleotide polymorphism (SNP) rs7639618 was subsequently found to be
      consistent and most significantly associated in Japanese and Han Chinese knee OA
      studies and functional relevant. Here, the association of the DVWA polymorphisms
      (rs7639618, rs11718863 and rs9864422) was genotyped in 1120 knee OA cases, 1482
      hip OA cases and 2147 controls, all of white European descent from the
      Netherlands, the UK, Spain and Greece. Random effect DerSimonian and Laird meta
      analyses were performed to assess the association in the different strata. To
      assess a more global effect, the original Japanese and Chinese data were included
      with the European. The meta-analyses provided evidence for global association of
      rs7639618 with knee OA with an odds ratio (OR) of 1.29, 95% confidence interval
      (CI) of 1.15-1.45 and a P-value of 2.70 x 10(-5). This effect, however, showed
      moderate heterogeneity, and rs7639618 was not independently associated with knee
      OA in Europeans, with an OR of 1.16, 95% CI of 0.99-1.35 and a P-value of 0.063.
      Furthermore, no association was observed with hip OA in Europeans, with a P-value
      of 0.851. Our results suggest that there may be global relevance for the DVWA SNP
      rs7639618 among knee OA cases, however, the apparent lower effect size in
      combination with the higher risk allele frequency in the European samples
      highlights again the ethnic differences in effects of discovered OA
      susceptibility genes.

PMID- 19181679
TI  - Depression Case Control (DeCC) Study fails to support involvement of the
      muscarinic acetylcholine receptor M2 (CHRM2) gene in recurrent major depressive
      disorder.
AB  - It has been suggested that alteration in the muscarinic-cholinergic system is
      involved in modulation of mood. Three studies have reported linkage on chromosome
      7 with major depressive disorder (MDD) in or close to a region containing the
      muscarinic receptor CHRM2 gene. A haplotype of SNPs located in CHRM2 (rs1824024
      rs2061174-rs324650) has been significantly associated with MDD in a previous
      study. We report the first study investigating this gene in a large, adequately
      powered, clinical depression case-control sample (n = 1420 cases, 1624 controls).
      Our data fail to support association with the CHRM2 polymorphisms previously
      implicated in the genetic aetiology of depression. It is possible our failure to
      replicate may be a consequence of differences in definition of the MDD phenotype
      and/or ethnic differences.

PMID- 19181680
TI  - Common variants in the region around Osterix are associated with bone mineral
      density and growth in childhood.
AB  - Peak bone mass achieved in adolescence is a determinant of bone mass in later
      life. In order to identify genetic variants affecting bone mineral density (BMD),
      we performed a genome-wide association study of BMD and related traits in 1518
      children from the Avon Longitudinal Study of Parents and Children (ALSPAC). We
      compared results with a scan of 134 adults with high or low hip BMD. We
      identified associations with BMD in an area of chromosome 12 containing the
      Osterix (SP7) locus, a transcription factor responsible for regulating osteoblast
      differentiation (ALSPAC: P = 5.8 x 10(-4); Australia: P = 3.7 x 10(-4)). This
      region has previously shown evidence of association with adult hip and lumbar
      spine BMD in an Icelandic population, as well as nominal association in a UK
      population. A meta-analysis of these existing studies revealed strong association
      between SNPs in the Osterix region and adult lumbar spine BMD (P = 9.9 x 10(
      11)). In light of these findings, we genotyped a further 3692 individuals from
      ALSPAC who had whole body BMD and confirmed the association in children as well
      (P = 5.4 x 10(-5)). Moreover, all SNPs were related to height in ALSPAC children,
      but not weight or body mass index, and when height was included as a covariate in
      the regression equation, the association with total body BMD was attenuated. We
      conclude that genetic variants in the region of Osterix are associated with BMD
      in children and adults probably through primary effects on growth.

PMID- 19181681
TI  - Support for the involvement of large copy number variants in the pathogenesis of
      schizophrenia.
AB  - We investigated the involvement of rare (<1%) copy number variants (CNVs) in 471
      cases of schizophrenia and 2792 controls that had been genotyped using the
      Affymetrix GeneChip 500K Mapping Array. Large CNVs >1 Mb were 2.26 times more
      common in cases (P = 0.00027), with the effect coming mostly from deletions (odds
      ratio, OR = 4.53, P = 0.00013) although duplications were also more common (OR =
      1.71, P = 0.04). Two large deletions were found in two cases each, but in no
      controls: a deletion at 22q11.2 known to be a susceptibility factor for
      schizophrenia and a deletion on 17p12, at 14.0-15.4 Mb. The latter is known to
      cause hereditary neuropathy with liability to pressure palsies. The same deletion
      was found in 6 of 4618 (0.13%) cases and 6 of 36 092 (0.017%) controls in the re
      analysed data of two recent large CNV studies of schizophrenia (OR = 7.82, P =
      0.001), with the combined significance level for all three studies achieving P =
      5 x 10(-5). One large duplication on 16p13.1, which has been previously
      implicated as a susceptibility factor for autism, was found in three cases and
      six controls (0.6% versus 0.2%, OR = 2.98, P = 0.13). We also provide the first
      support for a recently reported association between deletions at 15q11.2 and
      schizophrenia (P = 0.026). This study confirms the involvement of rare CNVs in
      the pathogenesis of schizophrenia and contributes to the growing list of specific
      CNVs that are implicated.

PMID- 19181683
TI  - CORNA: testing gene lists for regulation by microRNAs.
AB  - MOTIVATION: With the increasing use of post-genomics techniques to examine a wide
      variety of biological systems in laboratories throughout the world, scientists
      are often presented with lists of genes that they must make sense of. A
      consistently challenging problem is that of defining co-regulated genes within
      those gene lists. In recent years, microRNAs have emerged as a mechanism for
      regulating several cellular processes. In this article, we report on how gene
      lists and microRNA targets data may be integrated to test for significant
      associations between gene lists and microRNAs. RESULTS: We discuss CORNA, a
      package written in R and released under the GNU GPL, which allows users to test
      gene lists for significant microRNA-target associations using one of three
      separate statistical tests, to link microRNA targets to functional annotation and
      to visualize quantitative data associated with those data. AVAILABILITY: CORNA is
      available as an R package from http://corna.sf.net.

PMID- 19181684
TI  - Exploring phenotype-associated modules in an oral cavity tumor using an
      integrated framework.
AB  - MOTIVATION: Like most human diseases, tumors are complex traits, the genesis and
      development of which recruit a number of genes and several important biological
      processes. As proteins involved in common processes tend to be centralized in the
      same local area of protein-protein interaction networks, here a novel framework
      has been developed to identify which areas of the networks are most relevant to a
      phenotype. RESULTS: These areas termed 'coherent modules' can be regarded as gene
      sets dynamically defined in the networks. Compared with previous analogous
      approaches, one critical feature of our method is the optimization of coherent
      modules for two distinct aspects balanced by tuning a parameter in the framework.
      First, we seek the low coupling between coherent modules and then maximize the
      intrinsic similarity within a module. The framework has good expansibility, with
      classical expression data analysis methods generalized as particular cases. This
      coherent module approach was applied to an oral cavity tumor dataset with 18
      significant coherent modules identified, which could indicate the presence of
      lymph node metastasis. Further examination shows that most of the modules are
      responsible for comparatively independent biological processes. Our framework is
      helpful for the prognosis of tumors and offers a new perspective for tumor
      research. SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 19181682
TI  - Impairments in motor coordination without major changes in cerebellar plasticity
      in the Tc1 mouse model of Down syndrome.
AB  - Down syndrome (DS) is a genetic disorder arising from the presence of a third
      copy of human chromosome 21 (Hsa21). Recently, O'Doherty et al. [An aneuploid
      mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science
      309 (2005) 2033-2037] generated a trans-species aneuploid mouse line (Tc1) that
      carries an almost complete Hsa21. The Tc1 mouse is the most complete animal model
      for DS currently available. Tc1 mice show many features that relate to human DS,
      including alterations in memory, synaptic plasticity, cerebellar neuronal number,
      heart development and mandible size. Because motor deficits are one of the most
      frequently occurring features of DS, we have undertaken a detailed analysis of
      motor behaviour in cerebellum-dependent learning tasks that require high motor
      coordination and balance. In addition, basic electrophysiological properties of
      cerebellar circuitry and synaptic plasticity have been investigated. Our results
      reveal that, compared with controls, Tc1 mice exhibit a higher spontaneous
      locomotor activity, a reduced ability to habituate to their environments, a
      different gait and major deficits on several measures of motor coordination and
      balance in the rota rod and static rod tests. Moreover, cerebellar long-term
      depression is essentially normal in Tc1 mice, with only a slight difference in
      time course. Our observations provide further evidence that support the validity
      of the Tc1 mouse as a model for DS, which will help us to provide insights into
      the causal factors responsible for motor deficits observed in persons with DS.

PMID- 19181685
TI  - NOBLAST and JAMBLAST: New Options for BLAST and a Java Application Manager for
      BLAST results.
AB  - NOBLAST (New Options for BLAST) is an open source program that provides a new
      user-friendly tabular output format for various NCBI BLAST programs (Blastn,
      Blastp, Blastx, Tblastn, Tblastx, Mega BLAST and Psi BLAST) without any use of a
      parser and provides E-value correction in case of use of segmented BLAST
      database. JAMBLAST using the NOBLAST output allows the user to manage, view and
      filter the BLAST hits using a number of selection criteria. AVAILABILITY: A
      distribution package of NOBLAST and JAMBLAST including detailed installation
      procedure is freely available from http://sourceforge.net/projects/JAMBLAST/ and
      http://sourceforge.net/projects/NOBLAST. SUPPLEMENTARY INFORMATION: Supplementary
      data are available at Bioinformatics online.

PMID- 19181686
TI  - Assessment of smoking behaviors and alcohol use in the national social life,
      health, and aging project.
AB  - OBJECTIVES: The National Social Life, Health, and Aging Project (NSHAP) assessed
      smoking behaviors and alcohol use as factors directly related to physical health,
      well-being, and social relationships. We describe self-report measures of tobacco
      and alcohol use, as well as an established biological marker of tobacco exposure,
      cotinine, collected in Wave 1 of NSHAP. METHODS: We compare smoking behaviors and
      alcohol use by gender and age group. We report on derived measures of alcohol
      consumption and tobacco exposure widely used in medical and substance use
      literature, compare current and past users, and describe associations between
      self-reported smoking status and cotinine. RESULTS: Men are more likely than
      women to report alcohol use, potential problem drinking, and ever smoking.
      Alcohol use and smoking are lower among older age groups. Although current
      smoking is less prevalent than in the general U.S. adult population, 50% of
      current and 29% of past smokers have lifetime exposure of 40 pack-years or more.
      Cotinine is directly related to number of cigarettes per day but with
      considerable unexplained variation. Cotinine levels contradict self-report in
      fewer than 4% of nonsmokers. CONCLUSION: NSHAP provides data useful for
      investigation of smoking and alcohol use and their association with health and
      social factors.

PMID- 19181687
TI  - The long-term relationship between high-intensity volunteering and physical
      activity in older African American women.
AB  - OBJECTIVES: Experience Corps (EC) places older volunteers in public elementary
      schools in 20 cities across the country. The EC program in Baltimore is a health
      promotion intervention designed to improve the academic outcomes of children and
      increase older adult volunteer physical activity. We sought to determine if there
      were sustained increases in physical activity with participation in EC. METHODS:
      Seventy-one African American women volunteers in the Baltimore EC were compared
      with 150 African American women in the Women's Health and Aging Studies (WHAS) I
      and II; all were aged 65-86 years with comparable Social Economic Status,
      frailty, and self-reported health status. Using a regression model, we evaluated
      physical activity adjusting for a propensity score and time of follow-up over 3
      years. RESULTS: EC volunteers reported a sustained increase in physical activity
      as compared with the comparison cohort. Baseline physical activity for
      individuals with a median propensity score was 420 kcal/wk for both groups. At 36
      months, EC volunteers reported 670 kcal/week compared with 410 kcal/week in WHAS
      (p = .04). Discussion These findings suggest that high-intensity senior service
      programs that are designed as health promotion interventions could lead to
      sustained improvements in physical activity in high-risk older adults, while
      simultaneously addressing important community needs.

PMID- 19181688
TI  - Assessing outcome expectations in older adults: the multidimensional outcome
      expectations for exercise scale.
AB  - Outcome expectations, an important element of social cognitive theory, have been
      associated with physical activity in older adults. Yet, the measurement of this
      construct has often adopted a unidimensional approach. We examined the validity
      of a theoretically consistent three-factor (physical, social, and self
      evaluative) outcome expectations exercise scale in middle-aged and older adults
      (N = 320; M age = 63.8). Participants completed questionnaires assessing outcome
      expectations, physical activity, self-efficacy, and health status. Comparisons of
      the hypothesized factor structure with competing models indicated that a three
      factor model provided the best fit for the data. Construct validity was further
      demonstrated by significant association with physical activity and self-efficacy
      and differential associations with age and health status. Further evidence of
      validity and application to social cognitive models of physical activity is
      warranted.

PMID- 19181689
TI  - Journal of gerontology: psychological sciences. Editorial.

PMID- 19181690
TI  - Influence of sad mood and old age schema on older adults' attention to physical
      symptoms.
AB  - We examined how mood and activation of old age schema influenced attentional
      focus on physical symptoms in older adults. Seventy-one individuals aged 60 years
      or above participated in an experiment that manipulated mood and old age schema.
      They completed a modified Stroop task that measured attentional bias to physical
      symptoms. Controlling for baseline processing speed, the two variables had
      significant main and interaction effects on attentional focus on symptoms. Sad
      mood and old age schema independently minimized the bias to avoid attending to
      symptoms. When combined, these two variables contributed to greater attentional
      focus on symptoms. These findings highlight psychological influences on current
      attention to symptoms.

PMID- 19181691
TI  - Sibling death and death fear in relation to depressive symptomatology in older
      adults.
AB  - Previously overlooked factors in elders' depressive symptomatology were examined,
      including death fear, sibling death, and sibling closeness. Participants were 150
      elders (61 men, 89 women) aged 65-97 years with at least one sibling. Measures
      were proportion of deceased siblings, sibling closeness, the Death Fear Subscale
      of the Death Attitude Profile-Revised, and the Center for Epidemiological Studies
      Depression scale (20-item adult form). Age and education were exogenous variables
      in a structural equation model. Death fear, sibling closeness, and proportion of
      dead siblings were directly related to depression, with path coefficients of .42,
      -.24, and .13, respectively. Proportion of dead siblings had indirect effects on
      depression, as did age and education. Depressive symptomatology in old age is
      influenced by death fear related to sibling death as well as by poor
      relationships with them; it must be understood within a situational context
      including death fear and sibling relationships.

PMID- 19181692
TI  - A panel data analysis of the relationships of nursing home staffing levels and
      standards to regulatory deficiencies.
AB  - OBJECTIVE: To examine the relationships between nursing staffing levels and
      nursing home deficiencies. METHODS: This panel data analysis employed random
      effect models that adjusted for unobserved, nursing home-specific heterogeneity
      over time. Data were obtained from California's long-term care annual cost report
      data and the Automated Certification and Licensing Administrative Information and
      Management Systems data from 1999 to 2003, linked with other secondary data
      sources. RESULTS: Both total nursing staffing and registered nurse (RN) staffing
      levels were negatively related to total deficiencies, quality of care
      deficiencies, and serious deficiencies that may cause harm or jeopardy to nursing
      home residents. Nursing homes that met the state staffing standard received fewer
      total deficiencies and quality of care deficiencies than nursing homes that
      failed to meet the standard. Meeting the state staffing standard was not related
      to receiving serious deficiencies. CONCLUSIONS: Total nursing staffing and RN
      staffing levels were predictors of nursing home quality. Further research is
      needed on the effectiveness of state minimum staffing standards.

PMID- 19181693
TI  - Urban neighborhood context and change in depressive symptoms in late life.
AB  - OBJECTIVES: This study examines associations between urban neighborhood
      sociodemographic characteristics and change over time in late-life depressive
      symptoms. METHODS: Survey data are from three waves (1993, 1995, and 1998) of the
      Study of Assets and Health Dynamics Among the Oldest Old, a U.S. national
      probability sample of noninstitutionalized persons aged 70 years or older in
      1993. Neighborhoods are 1990 U.S. Census tracts. Hierarchical linear regression
      is used to estimate multilevel models. RESULTS: The average change over time in
      depressive symptoms varies significantly across urban neighborhoods. Change in
      depressive symptoms is significantly associated with neighborhood-level
      socioeconomic disadvantage and ethnic composition in unadjusted models but not in
      models that control for individual-level characteristics. CONCLUSIONS: Findings
      indicate that apparent neighborhood-level effects on change in depressive
      symptoms over time among urban-dwelling older adults reflect, for the most part,
      differences in characteristics of the neighborhood residents.

PMID- 19181694
TI  - Neighborhood characteristics and disability in older adults.
AB  - OBJECTIVE: To characterize the influence of the residential neighborhood of older
      adults on the prevalence of disability. METHODS: We combined Census data on
      disability in older adults living in New York City with environmental information
      from a comprehensive geospatial database. We used factor analysis to derive
      dimensions of compositional and physical neighborhood characteristics and linear
      regression to model their association with levels of disability. Measures of
      neighborhood collective efficacy were added to these models to explore the impact
      of the social environment. RESULTS: Low neighborhood socioeconomic status,
      residential instability, living in areas with low proportions of foreign born and
      high proportions of Black residents, and negative street characteristics were
      associated with higher prevalence of both "physical" disability and "going
      outside the home" disability. High crime levels were additionally associated with
      physical disability, although this relationship disappeared when misdemeanor
      arrests were removed from the crime variable. Low levels of collective efficacy
      were associated with more going-outside-the-home disability, with racial/ethnic
      composition dropping out of this model to be replaced by an interaction term.
      CONCLUSION: The urban environment may have a substantial impact on whether an
      older adult with a given level of functional impairment is able to age actively
      and remain independent.

PMID- 19181695
TI  - A common network in the left cerebral hemisphere represents planning of tool use
      pantomimes and familiar intransitive gestures at the hand-independent level.
AB  - Evidence from neuropsychology and neuroimaging implicates parietal and frontal
      areas of the left cerebral hemisphere in the representation of skills involving
      the use of tools and other artifacts. On the basis of neuropsychological data, it
      has been claimed that 1) independent mechanisms within the left hemisphere may
      support the representation of these skills (transitive actions) versus meaningful
      gestures that do not involve manipulating objects (intransitive actions), and 2)
      both cerebral hemispheres may participate in the representation of intransitive
      gestures. Functional magnetic resonance imaging was used to test these hypotheses
      in 12 healthy adults while they planned and executed tool use pantomimes or
      intransitive gestures with their dominant right (Exp. 1) or nondominant left
      (Exp. 2) hands. Even when linguistic processing demands were controlled, planning
      either type of action was associated with asymmetrical increases in the same
      regions of left parietal (the intraparietal sulcus, supramarginal gyrus, and
      caudal superior parietal lobule) and dorsal premotor cortices. Effects were
      greater for tool use pantomimes, but only when the right hand was involved.
      Neither group nor individual analyses revealed evidence for greater bilateral
      activity during intransitive gesture planning. In summary, at the hand
      independent level, transitive and intransitive actions are represented in a
      common, left-lateralized praxis network.

PMID- 19181697
TI  - Surgical outcomes of the modified single-patch technique in complete
      atrioventricular septal defect.
AB  - We examined the usefulness of the modified single-patch technique for the
      surgical management of complete atrioventricular septal defect (AVSD). Sixty-one
      patients undergoing total correction for complete AVSD from January 1997 to
      December 2006 were classified to the modified single-patch technique group (18
      patients) and the classical one-/two-patch technique group (43 patients). The
      surgical outcomes of the modified single-patch technique were compared with those
      of the classical-patch technique. Aortic cross-clamp time was shorter in the
      modified single-patch technique group (110.8+/-27.5 min vs. 134.4+/-42.5 min,
      P=0.03). During the follow-up period, two patients required reoperation for
      atrioventricular valve dysfunction in the modified single-patch technique group
      vs. three patients in the classical-patch technique group (P=0.63). One late
      death occurred in the modified single-patch technique and two late deaths in the
      classical-patch technique group (P=0.90). There was no significant difference in
      surgical outcomes between the two groups. And the modified single-patch technique
      has the advantage of relative simplicity and shorter ischemic time, and thus it
      is thought to be a feasible surgical option for the repair of complete AVSD.

PMID- 19181696
TI  - From phonemes to articulatory codes: an fMRI study of the role of Broca's area in
      speech production.
AB  - We used event-related functional magnetic resonance imaging to investigate the
      neuroanatomical substrates of phonetic encoding and the generation of
      articulatory codes from phonological representations. Our focus was on the role
      of the left inferior frontal gyrus (LIFG) and in particular whether the LIFG
      plays a role in sublexical phonological processing such as syllabification or
      whether it is directly involved in phonetic encoding and the generation of
      articulatory codes. To answer this question, we contrasted the brain activation
      patterns elicited by pseudowords with high- or low-sublexical frequency
      components, which we expected would reveal areas related to the generation of
      articulatory codes but not areas related to phonological encoding. We found
      significant activation of a premotor network consisting of the dorsal precentral
      gyrus, the inferior frontal gyrus bilaterally, and the supplementary motor area
      for low- versus high-sublexical frequency pseudowords. Based on our hypothesis,
      we concluded that these areas and in particular the LIFG are involved in phonetic
      and not phonological encoding. We further discuss our findings with respect to
      the mechanisms of phonetic encoding and provide evidence in support of a
      functional segregation of the posterior part of Broca's area, the pars
      opercularis.

PMID- 19181698
TI  - Early postoperative aortic rupture following surgery for acute type A aortic
      dissection.
AB  - We report our experience with patients who died of early aortic rupture following
      surgical treatment for acute type A aortic dissection in a consecutive series of
      324 patients who underwent surgery for this condition between 1991 and 2007. In
      hospital mortality rate was 9.9% (32/324), and seven patients (two men, mean age,
      67 years) died of postoperative aortic rupture. Rupture sites were the proximal
      aorta in two and distal aorta in five patients. Surgical procedures included
      ascending aorta replacement in six and ascending aorta plus aortic arch
      replacement in one. The common characteristics of the two patients with proximal
      aortic rupture were preoperative aortic insufficiency, intraoperative bleeding
      from the proximal stump, and high blood pressure before the rupture. In contrast,
      the distal aortic ruptures occurred in patients with uncomplicated postoperative
      courses, with three distal aortic ruptures occurring on the inpatient ward. The
      only common characteristic of the distal aortic ruptures was residual patent
      false lumen (80%, 4/5 patients), the other patient had a large pre-existing
      aneurysm in the descending thoracic aorta. Careful postoperative management,
      including strict blood pressure control, is especially important in patients with
      residual patent false lumen following surgery for acute type A aortic dissection.

PMID- 19181699
TI  - Tissue-resident stem cells promote breast cancer growth and metastasis.
AB  - Mesenchymal stem cells derived from bone marrow have recently been described to
      localize to breast carcinomas and to integrate into the tumor-associated stroma.
      In the present study, we investigated whether adipose tissue-derived stem cells
      (ASCs) could play a role in tumor growth and invasion. Compared with bone marrow
      derived cells, ASCs as tissue-resident stem cells are locally adjacent to breast
      cancer cells and may interact with tumor cells directly. Here, we demonstrate
      that ASCs cause the cancer to grow significantly faster when added to a murine
      breast cancer 4T1 cell line. We further show that breast cancer cells enhance the
      secretion of stromal cell-derived factor-1 from ASCs, which then acts in a
      paracrine fashion on the cancer cells to enhance their motility, invasion and
      metastasis. The tumor-promoting effect of ASCs was abolished by knockdown of the
      chemokine C-X-C receptor 4 in 4T1 tumor cells. We demonstrated that ASCs home to
      tumor site and promote tumor growth not only when co-injected locally but also
      when injected intravenously. Furthermore, we demonstrated that ASCs incorporate
      into tumor vessels and differentiate into endothelial cells. The tumor-promoting
      effect of tissue-resident stem cells was also tested and validated using a human
      breast cancer line MDA-MB-231 cells and human adipose tissue-derived stem cells.
      Our findings indicate that the interaction of local tissue-resident stem cells
      with tumor stem cells plays an important role in tumor growth and metastasis.

PMID- 19181700
TI  - Aberrant cell expansion in the elongation mutants of barley.
AB  - The elongation (elo) mutants of barley (Hordeum vulgare cv 'Himalaya') are a
      class of dwarf plants with defects affecting cell expansion. The phenotypes of
      mutants in three of the elo loci (elo1, elo2 and elo3) are recessive to the wild
      type allele, and the mutations at elo-4 and elo-5 are semi-dominant. Allelism
      tests showed that elo1, elo2 and elo3 were at separate loci, and mapping data
      indicated that elo-5 was possibly allelic to either elo1 or elo2. A phenotype
      common to all elo mutants was the presence of short, radially swollen cells on
      the leaf epidermis, indicating a defect in longitudinal cell expansion. In three
      of the mutants, elo1, elo3 and elo5, this was accompanied by a twisting growth
      habit. Two of the mutations, elo2 and elo-5, affected cell division, with
      aberrant periclinal cell division resulting in the formation of increased cell
      layers in the leaf epidermis of elo2 and elo-5 homozygotes and in the aleurone
      layer of elo2 grains. Misplaced anticlinal divisions also occurred in the elo-5
      leaf epidermis. Leaf cell walls of all elo lines contained less cellulose than
      the wild- type, and the cortical microtubules in elongating root epidermal cells
      in some elo lines were more randomly oriented than in the wild-type, consistent
      with the presence of radially swollen cells. We discuss possible functions for
      the Elo genes in primary cell wall synthesis.

PMID- 19181701
TI  - Integrating sequence with FPC fingerprint maps.
AB  - Recent advances in both clone fingerprinting and draft sequencing technology have
      made it increasingly common for species to have a bacterial artificial clone
      (BAC) fingerprint map, BAC end sequences (BESs) and draft genomic sequence. The
      FPC (fingerprinted contigs) software package contains three modules that maximize
      the value of these resources. The BSS (blast some sequence) module provides a way
      to easily view the results of aligning draft sequence to the BESs, and integrates
      the results with the following two modules. The MTP (minimal tiling path) module
      uses sequence and fingerprints to determine a minimal tiling path of clones. The
      DSI (draft sequence integration) module aligns draft sequences to FPC contigs,
      displays them alongside the contigs and identifies potential discrepancies; the
      alignment can be based on either individual BES alignments to the draft, or on
      the locations of BESs that have been assembled into the draft. FPC also supports
      high-throughput fingerprint map generation as its time-intensive functions have
      been parallelized for Unix-based desktops or servers with multiple CPUs.
      Simulation results are provided for the MTP, DSI and parallelization. These
      features are in the FPC V9.3 software package, which is freely available.

PMID- 19181702
TI  - Mitochondrial DNA level, but not active replicase, is essential for
      Caenorhabditis elegans development.
AB  - A number of studies showed that the development and the lifespan of
      Caenorhabditis elegans is dependent on mitochondrial function. In this study, we
      addressed the role of mitochondrial DNA levels and mtDNA maintenance in
      development of C. elegans by analyzing deletion mutants for mitochondrial
      polymerase gamma (polg-1(ok1548)). Surprisingly, even though previous studies in
      other model organisms showed necessity of polymerase gamma for embryonic
      development, homozygous polg-1(ok1548) mutants had normal development and reached
      adulthood without any morphological defects. However, polg-1 deficient animals
      have a seriously compromised gonadal function as a result of severe mitochondrial
      depletion, leading to sterility and shortened lifespan. Our results indicate that
      the gonad is the primary site of mtDNA replication, whilst the mtDNA of adult
      somatic tissues mainly stems from the developing embryo. Furthermore, we show
      that the mtDNA copy number shows great plasticity as it can be almost tripled as
      a response to the environmental stimuli. Finally, we show that the mtDNA copy
      number is an essential limiting factor for the worm development and therefore, a
      number of mechanisms set to maintain mtDNA levels exist, ensuring a normal
      development of C. elegans even in the absence of the mitochondrial replicase.

PMID- 19181704
TI  - Identification of a residue critical for the excision of 3'-blocking ends in
      apurinic/apyrimidinic endonucleases of the Xth family.
AB  - DNA single-strand breaks containing 3'-blocking groups are generated from attack
      of the sugar backbone by reactive oxygen species or after base excision by DNA
      glycosylase/apurinic/apyrimidinic (AP) lyases. In human cells, APE1 excises sugar
      fragments that block the 3'-ends thus facilitating DNA repair synthesis. In
      Leishmania major, the causal agent of leishmaniasis, the APE1 homolog is the
      class II AP endonuclease LMAP. Expression of LMAP but not of APE1 reverts the
      hypersensitivity of a xth nfo repair-deficient Escherichia coli strain to the
      oxidative compound hydrogen peroxide (H(2)O(2)). To identify the residues
      specifically involved in the repair of oxidative DNA damage, we generated random
      mutations in the ape1 gene and selected those variants that conferred protection
      against H(2)O(2). Among the resistant clones, we isolated a mutant in the
      nuclease domain of APE1 (D70A) with an increased capacity to remove 3'-blocking
      ends in vitro. D70 of APE1 aligns with A138 of LMAP and mutation of the latter to
      aspartate significantly reduces its 3'-phosphodiesterase activity. Kinetic
      analysis shows a novel role of residue D70 in the excision rate of 3'-blocking
      ends. The functional and structural differences between the parasite and human
      enzymes probably reflect a divergent molecular evolution of their DNA repair
      responses to oxidative damage.

PMID- 19181703
TI  - A rapid simple approach to quantify chromosome conformation capture.
AB  - Chromosome conformation capture (3C) is a powerful tool to study DNA looping. The
      procedure generates chimeric DNA templates after ligation of restriction enzyme
      fragments juxtaposed in vivo by looping. These unique ligation products (ULPs)
      are typically quantified by gel-based methods, which are practically inefficient.
      Taqman probes may be used, but are expensive. Cycle threshold (Ct) determined
      using SYBR Green, an inexpensive alternative, is hampered by non-specific
      products and/or background fluorescence, both due to high template/ULP ratio.
      SYBR Green melting curve analysis (MCA) is a well-known qualitative tool for
      assessing PCR specificity. Here we present for the first time MCA as a
      quantitative tool (qMCA) to compare template concentrations across different
      samples and apply it to 3C to assess looping among remote elements identified by
      STAT1 and IRF1 ChIP-chip at the interferon-gamma responsive CIITA and SOCS1 loci.
      This rapid, inexpensive approach provided highly reproducible identification and
      quantification of ULPs over a significant linear range. Therefore, qMCA is a
      robust method to assess chromatin looping in vivo, and overcomes several
      drawbacks associated with other approaches. Our data suggest that basal and
      induced looping is a involving remote enhancers is a common mechanism at IFNgamma
      regulated targets.

PMID- 19181705
TI  - DNA sampling: a method for probing protein binding at specific loci on bacterial
      chromosomes.
AB  - We describe a protocol, DNA sampling, for the rapid isolation of specific
      segments of DNA, together with bound proteins, from Escherichia coli K-12. The
      DNA to be sampled is generated as a discrete fragment within cells by the yeast I
      SceI meganuclease, and is purified using FLAG-tagged LacI repressor and beads
      carrying anti-FLAG antibody. We illustrate the method by investigating the
      proteins bound to the colicin K gene regulatory region, either before or after
      induction of the colicin K gene promoter.

PMID- 19181706
TI  - Scintillation proximity assay for measurement of RNA methylation.
AB  - Methylation of RNA by methyltransferases is a phylogenetically ubiquitous post
      transcriptional modification that occurs most extensively in transfer RNA (tRNA)
      and ribosomal RNA (rRNA). Biochemical characterization of RNA methyltransferase
      enzymes and their methylated product RNA or RNA-protein complexes is usually done
      by measuring the incorporation of radiolabeled methyl groups into the product
      over time. This has traditionally required the separation of radiolabeled product
      from radiolabeled methyl donor through a filter binding assay. We have adapted
      and optimized a scintillation proximity assay (SPA) to replace the more costly,
      wasteful and cumbersome filter binding assay and demonstrate its utility in
      studies of three distinct methyltransferases, RmtA, KsgA and ErmC'. In vitro,
      RmtA and KsgA methylate different bases in 16S rRNA in 30S ribosomal particles,
      while ErmC' most efficiently methylates protein-depleted or protein-free 23S
      rRNA. This assay does not utilize engineered affinity tags that are often
      required in SPA, and is capable of detecting either radiolabeled RNA or RNA
      protein complex. We show that this method is suitable for quantitating extent of
      RNA methylation or active RNA methyltransferase, and for testing RNA
      methyltransferase inhibitors. This assay can be carried out with techniques
      routinely used in a typical biochemistry laboratory or could be easily adapted
      for a high throughput screening format.

PMID- 19181707
TI  - Cardiogenic shock: to pump or not to pump?

PMID- 19181708
TI  - Treatment of heart failure in the elderly: never say it's too late.

PMID- 19181709
TI  - Skeletal muscle and mortality results from the InCHIANTI Study.
AB  - BACKGROUND: Sarcopenia, the age-related loss of muscle mass, may not be an
      isolated process but is associated with an increase in fat mass. The aim of this
      study was to estimate the mortality risk of sarcopenia in the presence or absence
      of obesity. METHODS: Data are from 934 participants aged 65 years or older,
      enrolled in the "Invecchiare in Chianti" study, and followed for 6 years. At
      baseline, a peripheral quantitative computerized tomography (pQCT) scan was
      performed on all participants to evaluate the muscle density, and the muscular
      and fat cross-sectional areas of the calf. Walking speed was measured on a 7-m
      track. Cox proportional hazard models were performed to estimate the association
      of pQCT measures (per 1 standard deviation increase) with mortality. RESULTS:
      Unadjusted analyses showed significant associations of muscle density (hazard
      ratio [HR] 0.78, 95% confidence interval [CI] 0.69-0.88), muscle area (HR 0.75,
      95% CI 0.66-0.86), and fat area (HR 0.82, 95% CI 0.73-0.92) with mortality. After
      adjustment for potential confounders, no body composition parameter was
      significantly associated with mortality. Walking speed (used as a reference
      measure to verify whether the negative results were due to peculiarities of the
      study sample) confirmed its well-established association with mortality risk (HR
      0.73, 95% CI 0.60-0.88). These results did not change after the analyses were
      stratified according to sarcopenia and body mass index groups, and restricted to
      participants with frailty or a high inflammatory profile. CONCLUSIONS: Calf
      skeletal muscle and fat mass are not significant risk factors for mortality in
      community-dwelling older adults. Walking speed confirmed to be a powerful
      predictor of health-related events.

PMID- 19181710
TI  - Normal aging involves modulation of specific inflammatory markers in the rat
      retina and choroid.
AB  - Recent work has suggested that inflammation is a common component of a number of
      age-related diseases. The hypothesis of the present study was that normal aging
      of the retina and choroid would increase levels of inducible nitric oxide
      synthase (iNOS), prostaglandin E2 (PGE2), and tumor necrosis factor alpha (TNF
      alpha). To investigate this hypothesis, gene expression and protein analyses were
      completed on retinal and choroidal samples from Fischer 344 x Brown Norway F1
      hybrid rats at 8, 22, and 32 months of age. Aging of the choroid produced
      significant increases in PGE2, with decreased TNF-alpha protein. Protein levels
      and messenger RNA of iNOS and TNF-alpha protein levels were significantly
      decreased in the aging retina in contrast to PGE2 protein activity, which was
      increased with age in the retina. These results suggest that PGE2 is likely
      involved in the aging process in both the retina and choroid, whereas iNOS plays
      a role predominantly in the retina.

PMID- 19181711
TI  - Driving status and three-year mortality among community-dwelling older adults.
AB  - BACKGROUND: Driving cessation can lead to myriad negative consequences for older
      adults. The purpose of these analyses was to examine driving status as a
      predictor of mortality among community-dwelling older adults. METHODS: This
      prospective cohort study included 660 community-dwelling adults ranging in age
      between 63 and 97 years. Between 2000 and 2004, participants completed
      performance-based assessments of vision, cognition, and physical abilities and
      indexes of health, depression, self-efficacy, and driving habits. Follow-up
      telephone interviews were completed approximately 3 years later. RESULTS: Among
      community-dwelling older adults, older age, health, poor near visual acuity,
      depressive symptoms, compromised cognitive status, and being a nondriver are
      associated with increased risk for a 3-year mortality. Nondrivers were four to
      six times more likely to die than drivers during the subsequent 3-year period.
      CONCLUSIONS: The ability to drive represents both a sign of cherished
      independence and underlying health and well-being for older adults. Retaining
      this ability is an important health concern in the United States.

PMID- 19181712
TI  - Development and validation of a short portable sarcopenia measure in the African
      American health project.
AB  - BACKGROUND: Poor muscle size and function (sarcopenia) have an important role in
      the age-associated disability process. However, no commonly accepted index of
      sarcopenia exists for use in epidemiological studies. METHODS: A cohort of 998
      community-dwelling African Americans 49-65 years' old at baseline was used to
      construct the short portable sarcopenia measure (SPSM). SPSM was conceptualized
      as a measure of sarcopenia that combines estimates of muscle quantity and
      function into a single scale, is based on component items that can be obtained
      easily in the field, represents muscle status at a single time point that can be
      used without sex-specific adjustments, and can be used to follow change in muscle
      status over time with each person as his or her own control. We used exploratory
      factor analysis (EFA) to identify a unidimensional scale based on timed chair
      rises, lean mass, and grip strength divided by height. We used these three items
      and their EFA factor weights to construct SPSM (mean 9.0, median 9, range 0
      [worst] to 18 [best] at baseline). Construct validity of the new measure, over a
      period of 36 months was examined. RESULTS: SPSM required 8.5 pounds of equipment
      and 12.4 minutes to complete. It showed good score distribution and convergent,
      discriminant, and predictive validity with measures of muscle function, body
      composition, physical performance, psychological factors, and functional
      limitation cross-sectionally and with muscle function and body composition
      longitudinally. Extensive sensitivity analyses confirmed SPSM's robustness.
      CONCLUSIONS: SPSM is a brief, portable, and valid measure of sarcopenia for use
      in epidemiological research. Similar studies in other populations are needed.

PMID- 19181713
TI  - Is there a role for new invertebrate models for aging research?

PMID- 19181714
TI  - Current thoughts on the role of mitochondria and free radicals in the biology of
      aging.

PMID- 19181715
TI  - The Lifestyle Interventions and Independence for Elders Pilot (LIFE-P): 2-year
      follow-up.
AB  - BACKGROUND: It is well recognized that physical activity (PA) is important for
      older adults; yet, clinicians remain pessimistic about the ability of older
      adults with compromised function to adhere to long-term treatment and to maintain
      behavior change once treatment has been terminated. METHODS: We examined the
      functional status of older adults at a field center (Wake Forest University) 2
      years after completing 12 months of treatment in the Lifestyle Interventions and
      Independence for Elders Pilot study. At baseline, participants were randomized to
      either a PA or a successful aging (SA) control group. Outcome measures included
      an interview assessment of PA, the Short Physical Performance Battery (SPPB), and
      performance on a 400-m self-paced walking test. RESULTS: Two years after the
      formal intervention had ended, participants who were originally in the PA group
      continued to engage in more minutes of moderate PA and tended to have better SPPB
      and walking speed than those in the SA group (effect sizes [ES]: SPPB = 0.40,
      walking speed = 0.37). Seven (12.7%) participants in the PA group failed the 400
      m walk at the 36-month follow-up assessment, whereas this number was 11 (21.6%)
      in the SA group. CONCLUSION: Older adults who have compromised physical function
      are able to sustain some of the benefits derived from participating in structured
      PA 2 years after supervised treatment has been terminated.

PMID- 19181716
TI  - Serum creatinine and functional limitation in elderly persons.
AB  - BACKGROUND: Creatinine is a commonly used measure of kidney function, but serum
      levels are also influenced by muscle mass. We hypothesized that higher serum
      creatinine would be associated with self-reported functional limitation in
      community-dwelling elderly. METHODS: Subjects (n = 1,553) were participants in
      the Study of Physical Performance and Age-Related Changes in Sonomans, a cohort
      to study aging and physical function. We explored three strategies to account for
      the effects of muscle mass on serum creatinine. RESULTS: We observed a J-shaped
      association of creatinine with functional limitation. Above the study-specific
      mean creatinine (0.97 mg/dL in women and 1.15 mg/dL in men), the unadjusted odds
      ratio of functional limitation per standard deviation (0.20 mg/dL in women and
      0.23 mg/dL in men) higher creatinine was 2.27 (95% confidence interval [CI] 1.75
      2.94, p < .001) in women and 1.42 (95% CI 1.12-1.80, p = .003) in men. This
      association was inverted in persons with creatinine levels below the mean.
      Adjustment for muscle mass did not have an important effect on the association
      between creatinine and functional limitation. These associations remained after
      multivariable adjustment for demographics and health conditions but were
      statistically significant only in women. CONCLUSIONS: In elderly adults, higher
      creatinine levels are associated with functional limitation, consistent with
      prior literature that has demonstrated reduced physical performance in persons
      with kidney disease. However, the association of low creatinine levels with
      functional limitation suggests that creatinine levels are influenced by factors
      other than kidney function and muscle mass in the elderly.

PMID- 19181717
TI  - Prevalence, awareness, and management of hypertension, dyslipidemia, and diabetes
      among United States adults aged 65 and older.
AB  - BACKGROUND: Adults aged 65 and older are disproportionately affected by
      hypertension, dyslipidemia, and diabetes, which are established risk factors for
      cardiovascular disease (CVD). Although risk reduction strategies among older
      adults, including control of CVD risk factors, can lead to a decline in premature
      CVD morbidity and mortality, the prevalence of these risk factors has generally
      increased in the past decade among elders and risk factor control rates have been
      suboptimal. We assess prevalence, awareness, treatment, and control rates among
      U.S. adults aged 65 and older with respect to hypertension, dyslipidemia, and
      diabetes and describe predictors associated with awareness and management of
      these factors. METHODS: Analysis of nationally representative data collected from
      adults aged 65 and older (n = 3,810) participating in the National Health and
      Nutrition Examination Survey 1999-2004. RESULTS: Women have a significantly
      higher prevalence of hypertension than men (76.6% vs 63.0%) and a significantly
      lower rate of control when treated pharmacologically (42.9% vs 57.9%).
      Dyslipidemia prevalence is 60.3% overall, and women are significantly more likely
      to be aware of their condition than men (71.1% vs 59.1%). Diabetes affects 21.2%
      of older adults, and 50.9% of prevalent cases are treated pharmacologically. Goal
      attainment among those treated is problematic for all three conditions
      hypertension (48.8%), dyslipidemia (64.9%), and diabetes (50.4%). Having two or
      more doctor visits annually is associated with goal attainment for dyslipidemia.
      CONCLUSIONS: Knowledge of cardiovascular health in older adults and understanding
      gender gaps in awareness can help physicians and policymakers improve disease
      management and patient education programs.

PMID- 19181718
TI  - APOE-epsilon4, depressive symptoms, and cognitive decline in Chinese older
      adults: Singapore Longitudinal Aging Studies.
AB  - BACKGROUND: The precise relationship between depression and cognitive decline in
      older adults is unclear. We investigated the influence of apolipoprotein E (APOE)
      epsilon4 genotype in modulating the effect of depressive symptoms on cognitive
      decline. METHODS: Prospective cohort study of 1,487 cognitively high-functioning
      Chinese older adults. Depressive symptoms (Geriatric Depression Scale score >/=5)
      and Mini-Mental State Examination (MMSE) were assessed at baseline, and cognitive
      decline (at least 1-point drop in MMSE) at 1-2 years after baseline. RESULTS:
      There was no significant difference in cognitive decline between depressed
      (32.9%) and nondepressed (31.5%) participants in the whole sample or among non
      APOE-epsilon4 carriers. Among APOE-epsilon4 carriers, depressed participants
      showed more cognitive decline (40.0%) than their nondepressed counterparts
      (28.6%), odds ratio = 2.89, 95% confidence interval: 1.03-8.12; p = .04, after
      controlling for age, gender, education, vascular risk factors/events, smoking,
      alcohol drinking, physical functioning, subjective memory complaint, length of
      follow-up, and baseline MMSE scores (p for interaction = .03). CONCLUSIONS: Our
      study suggests that the presence of the APOE-epsilon4 allele significantly
      enhanced the risk of cognitive decline associated with depressive symptoms. This
      finding should be independently replicated in future studies.

PMID- 19181719
TI  - The effect of speed-of-processing training on depressive symptoms in ACTIVE.
AB  - OBJECTIVE: We evaluated the effects of three cognitive training interventions on
      depressive symptoms at 1 and 5 years. METHODS: Advanced Cognitive Training for
      Independent and Vital Elderly is a multisite randomized controlled trial (age
      >or= 65 years), with four groups (memory, reasoning, speed-of-processing, and no
      contact control). Complete data were available for 2,014 (72%) and 1,516 (54%) of
      2,802 participants at 1 and 5 years. Separate propensity score models adjusted
      for potential attrition bias. Clinically important increases in depressive
      symptoms were defined as: (a) Center for Epidemiological Studies-Depression scale
      (CES-D)-12 score increases >or=0.5 SD and (b) CES-D-12 score increases >or=1.0
      SD. Multivariable logistic regression was used. RESULTS: The speed-of-processing
      group (vs the no-contact control group) was 30% less likely to experience
      clinically important increases in depressive symptoms at 1-year (adjusted odds
      ratio [AOR] = 0.700, p = .012) and 5-year (AOR = 0.698, p = .023) posttraining
      for the >or=0.5 SD threshold. Similar results (AOR = .669 with p = .039 at 1
      year; AOR = 0.651 with p = .059 at 5 years) were obtained for the >or=1.0 SD
      threshold. No differences were observed among the control, memory, or reasoning
      groups at either time period or at either threshold. CONCLUSION: The speed-of
      processing intervention reduced the risk of clinically important increases in
      depressive symptoms at 1- and 5-years postbaseline.

PMID- 19181720
TI  - Calcified right ventricular thrombus and antiphospholipid syndrome.
AB  - Antiphospholipid syndrome has been associated with venous and arterial thrombotic
      events but intracardiac thrombosis is rare. We describe a case about a 30-year
      old woman, admitted with a 6-month history of arthralgia, fatigue, and
      intermittent fever. Subsequent investigation revealed the presence of a large and
      calcified mass in the right ventricular outflow tract attached to the subvalvular
      tricuspid apparatus. Cardiac surgery was performed and histological examination
      demonstrated it to be composed entirely of calcified thrombus. Screening
      laboratory evaluation for hypercoagulable states confirmed the diagnosis of
      antiphospholipid syndrome.

PMID- 19181722
TI  - Ill equipped hospitals can't cope with casualties from Sri Lankan crisis.

PMID- 19181723
TI  - Government strategy on dementia will emphasise early diagnosis.

PMID- 19181721
TI  - Next generation tools for the annotation of human SNPs.
AB  - Computational biology has the opportunity to play an important role in the
      identification of functional single nucleotide polymorphisms (SNPs) discovered in
      large-scale genotyping studies, ultimately yielding new drug targets and
      biomarkers. The medical genetics and molecular biology communities are
      increasingly turning to computational biology methods to prioritize interesting
      SNPs found in linkage and association studies. Many such methods are now
      available through web interfaces, but the interested user is confronted with an
      array of predictive results that are often in disagreement with each other. Many
      tools today produce results that are difficult to understand without
      bioinformatics expertise, are biased towards non-synonymous SNPs, and do not
      necessarily reflect up-to-date versions of their source bioinformatics resources,
      such as public SNP repositories. Here, I assess the utility of the current
      generation of webservers; and suggest improvements for the next generation of
      webservers to better deliver value to medical geneticists and molecular
      biologists.

PMID- 19181725
TI  - NICE recommends long term campaign to encourage young people to exercise.

PMID- 19181728
TI  - Promoting breast feeding in the community.

PMID- 19181729
TI  - Effectiveness of policy to provide breastfeeding groups (BIG) for pregnant and
      breastfeeding mothers in primary care: cluster randomised controlled trial.
AB  - OBJECTIVE: To assess the clinical effectiveness and cost effectiveness of a
      policy to provide breastfeeding groups for pregnant and breastfeeding women.
      DESIGN: Cluster randomised controlled trial with prospective mixed method
      embedded case studies to evaluate implementation processes. SETTING: Primary care
      in Scotland. PARTICIPANTS: Pregnant women, breastfeeding mothers, and babies
      registered with 14 of 66 eligible clusters of general practices (localities) in
      Scotland that routinely collect breastfeeding outcome data. INTERVENTION:
      Localities set up new breastfeeding groups to provide population coverage;
      control localities did not change group activity. MAIN OUTCOME MEASURES:  PRIMARY
      OUTCOME: any breast feeding at 6-8 weeks from routinely collected data for two
      pre-trial years and two trial years. SECONDARY OUTCOMES: any breast feeding at
      birth, 5-7 days, and 8-9 months; maternal satisfaction. RESULTS: Between 1
      February 2005 and 31 January 2007, 9747 birth records existed for intervention
      localities and 9111 for control localities. The number of breastfeeding groups
      increased from 10 to 27 in intervention localities, where 1310 women attended,
      and remained at 10 groups in control localities. No significant differences in
      breastfeeding outcomes were found. Any breast feeding at 6-8 weeks declined from
      27% to 26% in intervention localities and increased from 29% to 30% in control
      localities (P=0.08, adjusted for pre-trial rate). Any breast feeding at 6-8 weeks
      increased from 38% to 39% in localities not participating in the trial. Women who
      attended breastfeeding groups were older (P<0.001) than women initiating breast
      feeding who did not attend and had higher income (P=0.02) than women in the
      control localities who attended postnatal groups. The locality cost was pound13
      400 (euro14 410; $20 144) a year. CONCLUSION: A policy for providing
      breastfeeding groups in relatively deprived areas of Scotland did not improve
      breastfeeding rates at 6-8 weeks. The costs of running groups would be similar to
      the costs of visiting women at home. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN44857041.

PMID- 19181730
TI  - Antenatal peer support workers and initiation of breast feeding: cluster
      randomised controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of an antenatal service using community
      based breastfeeding peer support workers on initiation of breast feeding. DESIGN:
      Cluster randomised controlled trial. SETTING: Community antenatal clinics in one
      primary care trust in a multiethnic, deprived population. PARTICIPANTS: 66
      antenatal clinics with 2511 pregnant women: 33 clinics including 1140 women were
      randomised to receive the peer support worker service and 33 clinics including
      1371 women were randomised to receive standard care. INTERVENTION: An antenatal
      peer support worker service planned to comprise a minimum of two contacts with
      women to provide advice, information, and support from approximately 24 weeks'
      gestation within the antenatal clinic or at home. The trained peer support
      workers were of similar ethnic and sociodemographic backgrounds to their clinic
      population. MAIN OUTCOME MEASURE: Initiation of breast feeding obtained from
      computerised maternity records of the hospitals where women from the primary care
      trust delivered. RESULTS: The sample was multiethnic, with only 9.4% of women
      being white British, and 70% were in the lowest 10th for deprivation. Most of the
      contacts with peer support workers took place in the antenatal clinics. Data on
      initiation of breast feeding were obtained for 2398 of 2511 (95.5%) women
      (1083/1140 intervention and 1315/1371 controls). The groups did not differ for
      initiation of breast feeding: 69.0% (747/1083) in the intervention group and
      68.1% (896/1315) in the control groups; cluster adjusted odds ratio 1.11 (95%
      confidence interval 0.87 to 1.43). Ethnicity, parity, and mode of delivery
      independently predicted initiation of breast feeding, but randomisation to the
      peer support worker service did not. CONCLUSION: A universal service for
      initiation of breast feeding using peer support workers provided within antenatal
      clinics serving a multiethnic, deprived population was ineffective in increasing
      initiation rates. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16126175.

PMID- 19181731
TI  - How to webcast lectures and conferences.

PMID- 19181733
TI  - Preventing transmission of maternally inherited mitochondrial DNA diseases.

PMID- 19181734
TI  - Fatty acid synthase: association with insulin resistance, type 2 diabetes, and
      cancer.
AB  - BACKGROUND: An emerging paradigm supports the notion that deregulation of fatty
      acid synthase (FASN)-catalyzed de novo FA biogenesis could play a central role in
      the pathogenesis of metabolic diseases sharing the hallmark of insulin
      resistance. CONTENT: We reviewed pharmacological and genetic alterations of FASN
      activity that have been shown to significantly influence energy expenditure
      rates, fat mass, insulin sensitivity, and cancer risk. This new paradigm proposes
      that insulin-resistant conditions such as obesity, type 2 diabetes, and cancer
      arise from a common FASN-driven "lipogenic state". An important question then is
      whether the development or the progression of insulin-related metabolic disorders
      can be prevented or reversed by the modulation of FASN status. If we accept the
      paradigm of FASN dysfunction as a previously unrecognized link between insulin
      resistance, type 2 diabetes, and cancer, the use of insulin sensitizers in
      parallel with forthcoming FASN inhibitors should be a valuable therapeutic
      approach that, in association with lifestyle interventions, would concurrently
      improve energy-flux status, ameliorate insulin sensitivity, and alleviate the
      risk of lipogenic carcinomas. CONCLUSIONS: Although the picture is currently
      incomplete and researchers in the field have plenty of work ahead, the latest
      clinical and experimental evidence that we discuss illuminates a functional and
      drug-modifiable link that connects FASN-driven endogenous FA biosynthesis,
      insulin action, and glucose homeostasis in the natural history of insulin
      resistant pathologies.

PMID- 19181735
TI  - A convenient LC-MS method for assessment of glucose kinetics in vivo with D
      [13C6]glucose as a tracer.
AB  - BACKGROUND: The isotope-labeled intravenous glucose tolerance test (IVGTT)
      combined with computer modeling is widely used to derive parameters related to
      glucose metabolism in vivo. Most of these methods involve use of either (2)H(2)
      labeled or (13)C(1)-labeled D-glucose as a tracer with GC-MS to measure the
      isotope enrichment. These methods are challenging, both technologically and
      economically. We have developed a novel approach that is suitable for labeled
      IVGTT studies involving a large cohort of individuals. METHODS: The tracer, D
      [(13)C(6)]glucose, is a low-cost alternative with the significant advantage that
      the sixth isotope of natural glucose has virtually zero natural abundance, which
      facilitates isotopomer analysis with <1% labeled glucose in the infusate. After
      deproteinization of plasma samples collected at various times, glucose is
      converted to a stable derivative, purified by solid-phase extraction (SPE), and
      analyzed by HPLC-electrospray ionization mass spectrometry to accumulate the
      isotope-abundance data for the A+2, A+3, and A+6 ions of the glucose derivative.
      A 2-pool modeling program was used to derive standard kinetic parameters.
      RESULTS: With labeled-IVGTT data from 10 healthy male individuals, the values for
      insulin sensitivity, glucose effectiveness, and the plasma clearance rate
      estimated with the 2-pool minimal model compared well with values obtained via
      traditional methods. CONCLUSIONS: The relative simplicity and robustness of the
      new method permit the preparation and analysis of up to 48 samples/day, a
      throughput equivalent to 2 complete IVGTT experiments, and this method is readily
      adaptable to existing 96 well-format purification and analytical systems.

PMID- 19181736
TI  - Point: use of pharmacogenetics in guiding treatment with warfarin.

PMID- 19181737
TI  - Rapid single-nucleotide polymorphism detection of cytochrome P450 (CYP2C9) and
      vitamin K epoxide reductase (VKORC1) genes for the warfarin dose adjustment by
      the SMart-amplification process version 2.
AB  - BACKGROUND: Polymorphisms of the CYP2C9 (cytochrome P450, family 2, subfamily C,
      polypeptide 9) gene (CYP2C9*2, CYP2C9*3) and the VKORC1 (vitamin K epoxide
      reductase complex, subunit 1) gene (-1639G>A) greatly impact the maintenance dose
      for the drug warfarin. Prescreening patients for their genotypes before
      prescribing the drug facilitates a faster individualized determination of the
      proper maintenance dose, minimizing the risk for adverse reaction and
      reoccurrence of thromboembolic episodes. With current methodologies, therapy can
      be delayed by several hours to 1 day if genotyping is to determine the loading
      dose. A simpler and more rapid genotyping method is required. METHODS: We
      developed a single-nucleotide polymorphism (SNP)-detection assay based on the
      SMart Amplification Process version 2 (SMAP 2) to analyze CYP2C9*2, CYP2C9*3, and
      VKORC1 -1639G>A polymorphisms. Blood from consenting participants was used
      directly in a closed-tube real-time assay without DNA purification to obtain
      results within 1 h after blood collection. RESULTS: We analyzed 125 blood samples
      by both SMAP 2 and PCR-RFLP methods. The results showed perfect concordance.
      CONCLUSIONS: The results validate the accuracy of the SMAP 2 for determination of
      SNPs critical to personalized warfarin therapy. SMAP 2 offers speed, simplicity
      of sample preparation, the convenience of isothermal amplification, and assay
      design flexibility, which are significant advantages over conventional genotyping
      technologies. In this example and other clinical scenarios in which genetic
      testing is required for immediate and better-informed therapeutic decisions, SMAP
      2-based diagnostics have key advantages.

PMID- 19181738
TI  - Profile of the circulating DNA in apparently healthy individuals.
AB  - BACKGROUND: Circulating nucleic acids (CNAs) have been shown to have diagnostic
      utility in human diseases. The aim of this study was to sequence and organize
      CNAs to document typical profiles of circulating DNA in apparently healthy
      individuals. METHODS: Serum DNA from 51 apparently healthy humans was extracted,
      amplified, sequenced via pyrosequencing (454 Life Sciences/Roche Diagnostics),
      and categorized by (a) origin (human vs xenogeneic), (b) functionality (repeats,
      genes, coding or noncoding), and (c) chromosomal localization. CNA results were
      compared with genomic DNA controls (n = 4) that were subjected to the identical
      procedure. RESULTS: We obtained 4.5 x 10(5) sequences (7.5 x 10(7) nucleotides),
      of which 87% were attributable to known database sequences. Of these sequences,
      97% were genomic, and 3% were xenogeneic. CNAs and genomic DNA did not differ
      with respect to sequences attributable to repeats, genes, RNA, and protein-coding
      DNA sequences. CNA tended to have a higher proportion of short interspersed
      nuclear element sequences (P = 0.1), of which Alu sequences were significant (P <
      0.01). CNAs had a significantly lower proportion of L1 and L2 long interspersed
      nuclear element sequences (P < 0.01). In addition, hepatitis B virus (HBV)
      genotype F sequences were found in an individual accidentally evaluated as a
      healthy control. CONCLUSIONS: Comparison of CNAs with genomic DNA suggests that
      nonspecific DNA release is not the sole origin for CNAs. The CNA profiling of
      healthy individuals we have described, together with the detailed biometric
      analysis, provides the basis for future studies of patients with specific
      diseases. Furthermore, the detection of previously unknown HBV infection suggests
      the capability of this method to uncover occult infections.

PMID- 19181739
TI  - Optimization of transrenal DNA analysis: detection of fetal DNA in maternal
      urine.
AB  - BACKGROUND: Fragments of DNA from cells dying throughout the body are detectable
      in urine (transrenal DNA, or Tr-DNA). Our goal was the optimization of Tr-DNA
      isolation and detection techniques, using as a model the analysis of fetal DNA in
      maternal urine. METHODS: We isolated urinary DNA using a traditional silica-based
      method and using a new technique based on adsorption of cell-free nucleic acids
      on Q-Sepharose resin. The presence of Y chromosome-specific SRY (sex-determining
      region Y) sequences in urine of pregnant women was detected by conventional and
      real-time PCR using primers/probe sets designed for 25-, 39-, 65-, and 88-bp PCR
      targets. RESULTS: Method of DNA isolation and PCR target size affected fetal Tr
      DNA detection. Assay diagnostic sensitivity increases as the PCR target is
      shortened. Shorter DNA fragments (50-150 bp) could be isolated by Q-resin-based
      technique, which also facilitated fetal Tr-DNA analysis. Using DNA isolated by Q
      resin-based method and an "ultrashort" DNA target, we successfully detected SRY
      sequences in 78 of 82 urine samples from women pregnant with male fetuses
      (positive predictive value 87.6%). Eleven of 91 urine samples from women pregnant
      with female fetuses produced SRY false-positive results (negative predictive
      value 95.2%). CONCLUSIONS: Single-copy fetal DNA sequences can be successfully
      detected in the urine of pregnant women when adequate methods for DNA isolation
      and analysis are applied. Strong precautions against sample contamination with
      male cells and DNA are necessary to avoid false-positive results.

PMID- 19181740
TI  - Hepatitis C virus: the growing challenge.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a major cause of liver disease worldwide.
      In industrialized countries, intravenous drug users (IDUs) are the main reservoir
      of infection. Relatively little information is available on HCV in the developing
      world. SOURCES OF DATA: Peer reviewed publications and presentations at major
      academic meetings. AREAS OF AGREEMENT: HCV-related cirrhosis and death from
      hepatocellular carcinoma are likely to rise dramatically in the next three
      decades. Urgent intervention is required both to minimize the burden of disease
      in those already infected and to reduce the incidence of new infections,
      particularly in the IDU population. AREAS OF CONTROVERSY: Current models of care
      and commissioning in the UK and other countries do not adequately identify or
      treat HCV infection in IDUs. Most strategies focus on disease prevention and do
      not target new infections. GROWING POINTS: New models of care are currently being
      developed and validated. AREAS TIMELY FOR DEVELOPING RESEARCH: The development of
      new models of HCV replication will transform our understanding and capacity to
      treat HCV infection.

PMID- 19181741
TI  - Preimplantation genetic screening outcomes are associated with culture
      conditions.
AB  - BACKGROUND: Although preimplantation genetic screening (PGS) is widely offered,
      there are contradictory reports on the clinical merit of this procedure. Any gain
      from embryo selection following aneuploidy screening must significantly outweigh
      the impact of the procedure. Variability of technical expertise in embryo biopsy,
      blastomere fixation, fluorescence in situ hybridization analysis, along with
      suboptimal laboratory quality control and inappropriate patient selection may
      impact PGS outcomes. METHODS: To investigate such effects, a total of 1508
      stimulated in vitro fertilization (IVF) cycles were retrospectively analysed.
      During 2004, a significant change was made to the embryo culture media used.
      Clinical outcomes from cycles with PGS were compared prior to and after the
      change in media and compared with matched controls not utilizing PGS during the
      same period. RESULTS: Clinical PGS success rates were found to improve following
      the media change. For patients aged less than 40, clinical outcomes following PGS
      were significantly lower than those without PGS prior to the change, but became
      equivalent after the change. For patients >or=40 years and <or=2 previous
      stimulated IVF cycles, clinical outcomes with PGS were similar to those without
      PGS prior to the change but became significantly improved after the change.
      CONCLUSION: These results suggest that a laboratory procedure change may
      significantly impact PGS patient outcomes.

PMID- 19181742
TI  - Adipose-derived stem cells from pregnant women show higher proliferation rate
      unrelated to estrogen.
AB  - BACKGROUND: Adipose tissue contains an abundant population of multipotent adipose
      derived stem cells (ASCs) and has been an excellent source of mesenchymal stem
      cells for cell therapy and tissue engineering. To ensure successful cell
      therapies, consistency of stem cell performance across donors is critical.
      However, the effect of the donor's reproductive status on ASC proliferation rate
      and differentiation capacity is undefined. METHODS: We investigated whether the
      yield and function of ASCs are affected by the woman's reproductive status:
      pregnancy, premenopause or menopause. ASCs were isolated from the abdomen of 15
      women and their proliferation rates and differentiation capacities were compared
      by cell count. The capacity of ASCs to differentiate into the chondrogenic
      lineage was investigated by quantitative real-time polymerase chain reaction and
      immunohistochemistry. RESULTS: There was no significant difference in the
      differentiation capacity between the three groups, whereas the proliferation rate
      of ASCs from pregnant women was significantly higher than from the other two
      groups (P < 0.05). The proliferation rate of ASCs after estrogen treatment
      remained unchanged. CONCLUSIONS: Despite the higher proliferation rate in
      pregnant women, ASCs showed consistency in cell differentiation capacity and were
      unaffected by donor status. This suggests that factors other than estrogen are
      responsible for the difference in proliferation.

PMID- 19181743
TI  - Heterogenous spectrum of CFTR gene mutations in Indian patients with congenital
      absence of vas deferens.
AB  - BACKGROUND: Mutations of the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene can cause congenital bilateral absence of vas deferens. Yet, the
      spectrum and frequency of CFTR mutations in Indian males with congenital absence
      of vas deferens (CAVD) is unknown. METHODS: We investigated 50 Indian males,
      diagnosed with unilateral or bilateral absence of vas deferens at the PGIMER,
      Chandigarh, for the presence of the most common CFTR gene mutations as well as
      unknown mutations by single-strand conformation polymorphism followed by sequence
      analysis. RESULTS: This study led to the identification of 12 CFTR gene mutations
      on 48% of 100 Indian CAVD chromosomes. CFTR mutations were identified on both
      alleles in 11 patients (22%) and on one allele in 26 patients (52%). Novel CFTR
      mutations identified were L69H, F87I, G126S, F157C, E543A, Y852F and D1270E. The
      T5 allele (25%) and F508del (11%) were the most common mutations identified. The
      most common intragenic marker haplotype for F508del was 2111 (GATT, TUB9, M470V
      and T854T). No mutations could be detected in 13 CAVD patients (26%), including 4
      with renal malformations. CONCLUSIONS: This study confirms the molecular
      heterogeneity of CFTR mutations in CAVD. Although the mutation detection rate is
      indeed lower in Indian CAVD patients, 74% of the patients tested had at least one
      CFTR mutation. CAVD alleles with no mutations suggest that other changes may be
      located at the non-screened sites that require extensive search by direct
      sequencing. Furthermore, the novel CFTR mutations identified require functional
      studies in a cell-based system.

PMID- 19181744
TI  - Cap-independent translation of human SP-A 5'-UTR variants: a double-loop
      structure and cis-element contribution.
AB  - Human surfactant protein A (hSP-A), a molecule of innate immunity and surfactant
      related functions, consists of two functional genes, SP-A1 and SP-A2. SP-A
      expression is regulated by several factors including environmental stressors. SP
      A1 and SP-A2 5'-untranslated region (5'-UTR) splice variants have a differential
      impact on translation efficiency and mRNA stability. To study whether these
      variants mediate internal ribosome entry site (IRES) activity (i.e., cap
      independent translation), we performed transient transfection experiments in H441
      cells with constructs containing one SP-A1 (A'D', AB'D', or A'CD') or SP-A2 (ABD)
      5'-UTR splice variant between the Renilla and firefly luciferase genes of a
      bicistronic reporter vector. We found that 1) variants A'D', ABD, and AB'D'
      exhibit significantly higher IRES activities than negative control (no SP-A 5'
      UTR) and A'CD' has no activity; the order of highest IRES activity was ABD > A'D'
      > AB'D; 2) IRES activity of ABD significantly increased in response to diesel
      particulate matter (20 microg/ml) but not in response to ozone (1 ppm for 1 h);
      3) deletion mutants of ABD revealed regulatory elements associated with IRES
      activity; one at the end of exon A attenuated activity, whereas a region
      containing a short adenosine-rich motif in the second half of exon B and the
      start of exon D enhanced activity; 4) elimination of a predicted double-loop
      structure or increase in free energy significantly reduced IRES activity; 5)
      elimination of one or both double-loop structures in A'D' did not affect cap
      dependent translation activity. Thus several factors, including cis-elements and
      secondary structure type and stability, are required for hSP-A 5'-UTR variant
      mediated cap-independent translation.

PMID- 19181745
TI  - Prolonged NO treatment decreases alpha-adrenoreceptor agonist responsiveness in
      porcine pulmonary artery due to persistent soluble guanylyl cyclase activation.
AB  - A cultured porcine pulmonary artery (PA) model was used to examine the effects of
      prolonged nitric oxide (NO) treatment on the response of this vessel to acutely
      applied NO and to the alpha-adrenoreceptor agonist phenylephrine. Two-hour
      treatment with the NO donor (Z)-1-[N-(2-aminoethyl)-N-(2
      ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO) decreased both NO and
      phenylephrine responsiveness. Twenty-four-hour treatment with DETA-NO resulted in
      a further reduction in NO responsiveness but no further reduction in
      phenylephrine responsiveness. Acute addition of soluble guanylyl cyclase (sGC)
      inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) had no effect on
      phenylephrine responsiveness in PA not treated with DETA-NO. ODQ treatment fully
      restored phenylephrine responsiveness in PA treated with DETA-NO. sGCbeta(1)
      subunit protein levels in PA tissue homogenate were 48.6 +/- 6.9, 51.6 +/- 3.5,
      and 41.3 +/- 2.8 ng/mg total protein for freshly prepared and 2-h and 24-h NO
      treated PA, respectively. Steady-state tissue cGMP was not significantly
      different in control versus NO-treated PA. sGC specific activity in the absence
      of added NO was measured in PA homogenate and was 0.29 +/- 0.02, 1.38 +/- 0.12,
      and 0.53 +/- 0.08 micromol cGMP.min(-1).mg sGC(-1), in freshly prepared and 2-h
      and 24-h NO treated PA, respectively. Ten-minute Hb treatment completely
      normalized sGC basal activity in homogenates prepared from DETA-NO-treated PA,
      which was 0.23 +/- 0.02, 0.18 +/- 0.03, and 0.25 +/- 0.04 micromol cGMP.min(
      1).mg sGC(-1), in freshly prepared and 2-h and 24-h NO-treated PA, respectively.
      The kinetics of the Hb reversal of NO-mediated sGC persistent activation do not
      support sGC covalent modification as the activation mechanism. We conclude that
      prolonged NO exposure results in a persistently increased sGC specific activity,
      which accounts for the observed alpha-adrenoreceptor agonist hyporesponsiveness.

PMID- 19181747
TI  - Molecular phylogenetics and the evolution of fruit and leaf morphology of Dichaea
      (Orchidaceae: Zygopetalinae).
AB  - BACKGROUND AND AIMS: The orchid genus Dichaea, with over 100 species found
      throughout the neotropics, is easily recognized by distichous leaves on long
      stems without pseudobulbs and flowers with infrastigmatic ligules. The genus has
      previously been divided into four sections based primarily on presence of ovary
      bristles and a foliar abscission layer. The aim of this work is to use DNA
      sequence data to estimate phylogenetic relationships within Dichaea and map the
      distribution of major morphological characters that have been used to delimit
      subgenera/sections. METHODS: Sequence data for the nuclear ribosomal internal
      transcribed spacers and plastid matK, trnL intron, trnL-F spacer and ycf1 for 67
      ingroup and seven outgroup operational taxonomic units were used to estimate
      phylogenetic relationships within Dichaea. Taxa from each of the four sections
      were sampled, with the greatest representation from section Dichaea, the most
      diverse and taxonomically puzzling group. KEY RESULTS: Molecular data and
      morphology support monophyly of Dichaea. Results indicate that section
      Dichaeopsis is polyphyletic and based on symplesiomorphies, including deciduous
      leaves and smooth ovaries that are widespread in Zygopetalinae. There are at
      least three well-supported clades within section Dichaeopsis. Section
      Pseudodichaea is monophyletic and defined by setose ovaries and leaves with an
      abscission layer. Sections Dichaea and Dichaeastrum are monophyletic and defined
      by pendent habit and persistent leaves. Section Dichaeastrum, distinguished from
      section Dichaea primarily by a glabrous ovary, is potentially polyphyletic.
      CONCLUSIONS: The leaf abscission layer was lost once, occurring only in the
      derived sections Dichaea and Dichaeastrum. The setose fruit is a more
      homoplasious character with several losses and gains within the genus. We propose
      an informal division of the genus based upon five well-supported clades.

PMID- 19181746
TI  - Lipopolysaccharide-dependent interaction between PU.1 and c-Jun determines
      production of lipocalin-type prostaglandin D synthase and prostaglandin D2 in
      macrophages.
AB  - Previously, we reported that expression of lipocalin-prostaglandin D synthase (L
      PGDS) is inducible in macrophages and protects from Pseudomonas pneumonia. Here,
      we investigated the mechanism by which L-PGDS gene expression is induced in
      macrophages. A promoter analysis of the murine L-PGDS promoter located a binding
      site of PU.1, a transcription factor essential for macrophage development and
      inflammatory gene expression. A chromatin immunoprecipitation assay showed that
      PU.1 bound to the cognate site in the endogenous L-PGDS promoter in response to
      LPS. Overexpression of PU.1, but not of PU.1(S148A), a mutant inert to casein
      kinase II (CKII) or NF-kappaB-inducing kinase (NIK), induced L-PGDS in RAW 264.7
      cells. Conversely, siRNA silencing of PU.1 expression blunted productions of L
      PGDS and prostaglandin D2 (PGD(2)). LPS treatment induced formation of the
      complex of PU.1 and cJun on the PU.1 site, but inactivation of cJun by treatment
      with JNK or p38 kinase inhibitor abolished the complex, and suppressed PU.1
      transcriptional activity for L-PGDS gene expression. Together, these results show
      that PU.1, activated by CKII or NIK, cooperates with MAPK-activated cJun to
      maximally induce L-PGDS expression in macrophages following LPS treatment, and
      suggest that PU.1 participates in innate immunity through the production of L
      PGDS and PGD(2).

PMID- 19181748
TI  - Limited mate availability decreases reproductive success of fragmented
      populations of Linnaea borealis, a rare, clonal self-incompatible plant.
AB  - BACKGROUND AND AIMS: Small populations of rare plant species are increasingly
      reported to have high levels of reproductive failure. The objective of this study
      was to understand the principal constraints on sexual reproduction in small
      fragmented populations of a rare clonal self-incompatible plant. METHODS: The
      pollinator spectrum, diversity of flower colour, natural pollination and fruit
      set levels of L. borealis were examined in Scotland. Artificially crossed seed
      production was compared within and between different flower colour types and
      patches. KEY RESULTS: Linnaea borealis was pollinated by a diverse spectrum of
      insect species and the principal pollinators were muscid, syrphid and empid flies
      which mostly moved only small distances (<0.25 m) between flowers when foraging.
      Natural pollination levels were high, indicating high pollinator effectiveness,
      but fruit set was very low in most patches. Flower colour diversity was low in
      most patches and only those with a diversity of flower colour types had high
      fruiting success. Pollination experiments showed L. borealis to be highly self
      incompatible and artificial crosses within and between patches and flower colour
      types confirmed that low fruit success was the result of a lack of compatible
      mates and limited pollen movement between them. Evidence of isolation from pollen
      exchange was apparent at as little as 6 m and severe at 30 m and beyond.
      CONCLUSIONS: Limited mate availability and isolation from pollen exchange
      compromise the reproductive success of fragmented populations of L. borealis in
      Scotland. A diversity of compatible mates situated within close proximity (<6 m)
      is the key requirement to ensure high natural fruiting success. This study
      emphasizes that an understanding of the breeding system, pollinator spectrum and
      potential for interconnectivity via pollinator movement are fundamental to
      identify isolation distances and to establish when conservation intervention is
      necessary for rare species.

PMID- 19181749
TI  - The effect of temperature on mortality in rural Bangladesh--a population-based
      time-series study.
AB  - BACKGROUND: Studies in urban cities have consistently shown evidence of increased
      mortality in association with hot and cold weather. However, few studies have
      examined temperature-mortality relationship in the rural areas of developing
      countries. In this study we therefore aimed to characterize the daily temperature
      mortality relationships in rural Bangladesh. METHODS: A generalized linear
      Poisson regression model was used to regress a time-series of daily mortality for
      all-cause and selected causes against temperature, controlling for seasonal and
      interannual variations, day of week and public holidays. A total of 13 270 all
      cause deaths excluding external causes for residents under demographic
      surveillance in Matlab, Bangladesh were available between January 1994 and
      December 2002. RESULTS: There was a marked increase in all-cause deaths and
      deaths due to cardiovascular, respiratory and perinatal causes at low
      temperatures over a lag of 0-13 days. Every 1 degrees C decrease in mean
      temperature was associated with a 3.2% (95% CI 0.9-5.5) increase in all-cause
      mortality. However, there was no clear heat effect on all-cause mortality for any
      of the lags examined. CONCLUSIONS: This study found that daily mortality
      increased with low temperatures in the preceding weeks, while there was no
      association found between high temperatures and daily mortality in rural
      Bangladesh. Preventive measures during low temperatures should be considered
      especially for young infants.

PMID- 19181750
TI  - Editorial.

PMID- 19181751
TI  - A cardioplegia circuit with versatility: the 'ReVerse' system. How to do it.
AB  - Various methods of cardioplegia administration have been used in cardiac surgery:
      crystalloid, blood and mixed crystalloid/blood. Each of these types of
      cardioplegia administration typically needs a different circuit. This may
      correspond to an increase in cost and the time needed to change the circuit if
      required. When various modifications are performed on the circuit, this also
      increases the risk of contamination. In order to simplify the management of
      differing cardioplegia circuits, we devised one circuit for all solutions in all
      situations by adding one modification. The ReVerse cardioplegia circuit system is
      a description of a two-pump cardioplegia circuit which is adaptable to either
      blood or crystalloid cardioplegia. The change from one mode to another requires a
      manoeuvre of two clamps, allowing the blood solution to travel through shunt
      tubing into the apposite pumphead. In our experience the versatility of this
      circuit is a fast, safe method to administrate all types of cardioplegia
      solution, saving the space taken up by storing multiple circuits.

PMID- 19181752
TI  - Initial clinical experience with the admiral oxygenator combined with separated
      suction.
AB  - The Admiral, a new microporous membrane oxygenator with a low surface area,
      decreased priming volume and two separate reservoirs, was tested in 30 adult
      patients. This study was undertaken to evaluate blood path resistance, gas
      exchange capabilities and blood trauma in clinical use, with and without shed
      blood separation. Patients were divided into 3 groups. Group 1 had valve surgery
      without separation of suction, Group 2 had coronary artery bypass grafting (CABG)
      with direct blood aspiration and Group 3 had coronary artery bypass grafting with
      shed blood separation. The suctioned, separated, cardiotomy blood in Group 3 was
      treated with an autotransfusion device at the end of bypass before being returned
      to the patient. Theoretical blood flow could be achieved in all cases without
      problem. The pressure drop through the oxygenator averaged 88 +/- 13 mmHg at 4
      l/min and 109 +/- 12 mmHg at 5 l/min. O(2) transfer was 163 +/- 27 ml/min. Free
      plasma haemoglobin rose in all groups, but significantly less in group 3. Lactate
      dehydrogenase (LDH) rose significantly in Groups 1 and 2. Platelets decreased in
      all groups without significant differences. Clinical experience with this new
      oxygenator was safe, the reduced membrane surface did not impair gas exchange and
      blood trauma could be minimized easily by separating shed blood, using the second
      cardiotomy reservoir.

PMID- 19181753
TI  - Interaction of plasma proteins with commercial protein repellent polyvinyl
      chloride (PVC): a word of caution.
AB  - Protein adsorption onto polymers remains a problem. In recent years, several
      protein-repellent PVC tubings have been developed. Although several studies
      report the interaction between plasma coagulation proteins and PVC, few address
      the interaction with other plasma proteins. Two commercial brands of untreated
      medical grade PVC tubing, phosphorylcholine-coated PVC tubing, triblock-copolymer
      (polycaprolactone-polydimethylsiloxane-polycaprolactone)-treated PVC tubing and
      poly-2-methoxyethylacrylate (PMEA)-coated tubing were exposed for 60 minutes to
      human plasma. A broad spectrum of plasma proteins was found on all tubing. The
      adsorbed albumin to total protein ratio is lower than the similar ratio in plasma
      while alpha1 and alpha2 globulins are over-represented in the protein spectrum.
      On PMEA tubing, not only alpha globulins, but also beta and gamma globulins, are
      found in high concentrations in the adsorbed protein. PMEA tubing and uncoated
      PVC tubing of brand B had a higher amount of protein adsorbed compared against
      all other tubing (p < 0.05). There were no statistical differences in protein
      adsorption between the triblock-copolymer-treated tubing, the phosphorylcholine
      coated tubing and the uncoated PVC tubing of brand A. The average thickness of
      the protein layer was 23 nm. Plasma protein adsorption still exists on uncoated
      and protein-repellent tubing and can initiate a systemic inflammatory reaction.

PMID- 19181754
TI  - Intra-aortic balloon pumping increases renal blood flow in patients with low left
      ventricular ejection fraction.
AB  - Intra-aortic balloon pumping (IABP) has, for decades, been one of the key
      treatment modalities following impaired cardiac function after cardiac surgery.
      IABP increases cardiac output, decreases oxygen consumption of the heart and
      relieves the left ventricle. However, a number of complications have been
      reported in connection with IABP treatment. Only a few studies have evaluated
      renal blood flow and the purpose of this prospective study was to evaluate
      whether renal blood flow was affected by IABP treatment in high-risk patients.
      After approval from the county ethical committee and informed consent, seven
      consecutive patients with low left ventricular ejection fraction and scheduled
      for preoperative IABP treatment were allocated to the study. Assessment of renal
      blood flow was based on ultrasound spectral Doppler estimation of the flow
      velocity profiles in the interlobar kidney arteries. The result was described as
      balloon index (BI), which is maximal systolic velocity divided by the temporal
      mean velocity. Typical velocity profiles were demonstrated in all patients
      before, during and after IABP. BI measurement changed with time (p <0.05). BI was
      lower during IABP compared to both pre-IABP and post-IABP (p <0.025), indicating
      a higher renal blood flow. No statistically significant changes were seen in s
      creatinine or creatinine clearance. Assuming unchanged diameter of kidney
      arteries and no considerable decrease in renal resistance and/or compliance, we
      conclude that the interlobar renal blood flow was significantly increased during
      IABP treatment, measured by ultrasound Doppler technique, but without a
      simultaneously significant change in creatinine clearance.

PMID- 19181755
TI  - Differences in displayed pump flow compared to measured flow under varying
      conditions during simulated cardiopulmonary bypass.
AB  - Errors in blood flow delivery due to shunting have been reported to reduce flow
      by, potentially, up to 40-83% during cardiopulmonary bypass. The standard roller
      pump measures revolutions per minute and a calibration factor for different
      tubing sizes calculates and displays flow accordingly. We compared displayed
      roller-pump flow with ultrasonically measured flow to ascertain if measured flow
      correlated with the heart-lung pump flow reading. Comparison of flows was
      measured under varying conditions of pump run duration, temperature, viscosity,
      varying arterial/venous loops, occlusiveness, outlet pressure, use of silicone or
      polyvinyl chloride (PVC) in the roller race, different tubing diameters, and use
      of a venous vacuum-drainage device.

PMID- 19181756
TI  - Comparison of isoproterenol and dobutamine in the induction of cardiac
      hypertrophy and fibrosis.
AB  - Isoproterenol (Iso) was a clinical therapeutic that is now used as a research
      means for the induction of cardiac hypertrophy. Currently, dobutamine (Dob) has
      replaced Iso as the preferred inotropic beta-adrenergic agent to wean patients
      from cardiopulmonary bypass and to sustain adequate cardiac function during the
      postoperative period. We sought to compare the cardiac structural and functional
      effects of long-term administration (7days) of Iso with Dob at a dose of
      40microg/mouse/day in 12-week-old C57BL/6 female mice. Cardiac function was
      determined with transthoracic echo cardiography (ECHO) 24 hours after the last
      dose. Cardiac wet weights increased 33% and 24% in the Iso and Dob groups
      compared with controls (p < 0.05). Dob and Iso significantly increased cardiac
      fibrosis and decreased cardiac function with chronic administration.
      Administration also resulted in increased left atrial size, suggesting that both
      Dob and Iso decreased LV compliance, but did not induce heart failure. In
      conclusion, chronic administration of Dob may have a detrimental effect on
      cardiac structure and function.

PMID- 19181757
TI  - The effect of daily administration of IL-18 on cardiac structure and function.
AB  - Recently, the cytokine Interleukin-18 (IL-18) has been shown to be increased as a
      result of cardiac surgery. Elevated IL-18 has been associated with neurological
      dysfunction, systemic inflammatory response syndrome (SIRS), and multiple organ
      dysfunction syndrome (MODS) post open-heart surgery. The intent of the study
      contained herein was to determine the effect of IL-18 administration on cardiac
      function and structure. Eight C57BL/6 female mice were treated daily with
      0.5microg/mouse of recombinant IL-18 for 7 days. Long axis echocardiography
      (ECHO) measurements of the anatomical and hemodynamic function of the heart for
      all mice were studied 24h after the last dose. The left ventricular wet weights
      increased from 84 +/- 1 to 93 +/- 3 mg when comparing the placebo (n = 8) with
      the IL-18 groups, respectively (p = 0.01). With ECHO analysis, IL-18
      significantly increased left ventricular (LV) mass, the left atrium dimensions
      (LA), and the left ventricular posterior wall thickness (LVPW) over the 8-day
      time period (p < 0.01). There was a 5-fold increase in interstitial cardiac
      collagen content and a 30% increase in myocyte size in the IL-18 compared with
      the control groups (p < 0.01). Administration of IL-18 appears to induce
      interstitial fibrosis and myocyte hypertrophy, resulting in increased ventricular
      stiffness. Thus, increased IL-18 during and post open-heart surgical procedures
      may induce left ventricular diastolic dysfunction and affect post-operative
      outcomes.

PMID- 19181758
TI  - Cardiopulmonary bypass and deep hypothermic circulatory arrest in a massively
      obese patient.
AB  - As a consequence of the rising global prevalence and magnitude of obesity, a
      greater proportion of patients presenting for cardiac surgery is morbidly obese.
      Being overweight (body mass index; BMI 25-29.9 kg/m(2)) or obese (BMI 30-35
      kg/m(2)) appears to confer some survival benefit following cardiac surgery. By
      contrast, morbid obesity (BMI >40 kg/m(2)) is associated with an increased
      likelihood of postoperative complications and prolonged intensive care unit and
      hospital length of stay. The physical difficulties encountered when managing this
      group of patients is exemplified by those undergoing complex, multiple procedures
      requiring prolonged cardiopulmonary bypass (CPB) and deep hypothermic circulatory
      arrest (DHCA). We present the successful management of a massively obese 19-year
      old male (BMI 45 kg/m(2)) with Marfan's syndrome who required aortic root and
      arch replacement under DHCA. The selection of extracorporeal circuit components
      to accommodate a large circulating volume and permit high CPB flow rates (>9
      l/min) is discussed.

PMID- 19181760
TI  - Predicting mortality and uptake of renal replacement therapy in patients with
      stage 4 chronic kidney disease.
AB  - BACKGROUND: Novel strategies are required to efficiently manage the increasing
      number of patients diagnosed with chronic kidney disease (CKD). We sought to
      identify factors predicting outcome in patients with stage 4 CKD and to determine
      whether low-risk patients could be managed in primary care. METHODS: We performed
      a two-centre, retrospective cohort study including 396 patients with stage 4 CKD
      referred to nephrology clinics from 1998 to 2002. We utilized electronic
      databases to determine the incidence of renal replacement therapy (RRT) and
      mortality and the rate of deterioration in estimated glomerular filtration rate
      (eGFR) to the year end 2005. RESULTS: This was an elderly cohort, with 71.7% of
      patients aged > or =65 years. The risk of surviving to require dialysis fell with
      increasing age (HR 0.44; 95% CI: 0.23-0.84 for those >74 years verses those <65
      years), in part due to the slower rate of decline in renal function in older
      patients (median fall in eGFR was -2.25, -1.38 and -0.86 ml/ min/1.73 m(2)/year
      in those aged <65 years, 65-74 years and >74 years, respectively, P < 0.0001).
      Additional independent risk factors predicting RRT included: high baseline
      proteinuria (HR 6.26; 95% CI: 2.74-14.23 for >3 g/24 h versus <0.3 g/24 h),
      greater early decline in renal function (HR 3.86; 95% CI: 2.34-6.38 for > or =4
      ml/min/1.73 m(2)/year versus <4 ml/min/1.73 m(2)/year), low baseline eGFR (HR
      2.92; 95% CI: 1.61-5.30 for 15-19 versus 25-29 ml/min/1.73 m(2)) and low
      haemoglobin (HR 3.16; 95% CI: 1.64-6.08 for <10 versus >12 g/dl). The 98 (24.7%)
      patients discharged to primary care had more stable renal function than those
      remaining under nephrology care (median change in eGFR of +0.20 versus -1.88 ml/
      min/1.73 m(2)/year, P = 0.0001). CONCLUSIONS: Most patients with stage 4 CKD, in
      particular the elderly, die without commencing RRT. Patients at low risk of
      progression can be identified and discharged safely to primary care with an
      active management plan.

PMID- 19181759
TI  - Long-term treatment with cinacalcet and conventional therapy reduces parathyroid
      hyperplasia in severe secondary hyperparathyroidism.
AB  - BACKGROUND: The effect of cinacalcet on the structural pattern of hyperplastic
      parathyroid glands was evaluated, using high-resolution colour Doppler (CD)
      sonography, in haemodialysis patients with severe, inadequately controlled,
      secondary hyperparathyroidism (sHPT). METHODS: Nine patients (6 males, 3 females;
      mean age +/- SD, 55.5 +/- 12.6 years) received cinacalcet, with adaptation of
      existing concomitant therapies. Biochemical parameters and the morphology and
      vascular pattern of hyperplastic parathyroid glands were measured at baseline and
      every 6 months thereafter, for a follow-up period of 24-30 months. RESULTS: At
      baseline, 28 hyperplastic glands were identified. Cinacalcet led to a reduction
      in glandular volume during the course of the study: 68% in glands with a baseline
      volume <500 mm(3) and 54% in glands with a baseline volume >or=500 mm(3). The
      mean volume +/- SD of glands <500 mm(3) changed significantly from the baseline
      (233 +/- 115 mm(3)) to the end of follow-up (102 +/- 132 mm(3), P = 0.007).
      Levels of mean serum phosphorus, calcium and calcium-phosphorus product
      decreased, but not significantly, whereas there were significant decreases in
      mean parathyroid hormone +/- SD levels (1196 +/- 381 pg/ml versus 256 +/- 160
      pg/ml; P < 0.0001) and alkaline phosphatase +/- SD levels (428 +/- 294 versus 223
      +/- 88 IU/l; P = 0.04), accompanied by an improvement in a subjective clinical
      score. CONCLUSIONS: Cinacalcet, in combination with conventional treatments, led
      to an improvement in biochemical and clinical parameters of sHPT and reduced
      glandular volume in patients with severe sHPT. Volume reduction was more evident
      in smaller glands. Longer term, larger, randomized clinical trials are needed to
      confirm these preliminary findings and to further define a more systematic
      approach in the treatment of sHPT.

PMID- 19181761
TI  - Salt wars.

PMID- 19181762
TI  - Microbial inactivation properties of a new antimicrobial/antithrombotic catheter
      lock solution (citrate/methylene blue/parabens).
AB  - BACKGROUND: Microbial infections are the most serious complications associated
      with indwelling central venous catheters. A catheter lock solution that is both
      antibacterial and antithrombotic is needed. The goal of this study was to
      determine whether a new catheter lock solution containing citrate, methylene blue
      and parabens has antimicrobial properties against planktonic bacteria and against
      sessile bacteria within a biofilm. These effects were compared to the
      antimicrobial properties of heparin at 2500 units/ml. METHODS: The tested
      solution (C/MB/P comprising 7% sodium citrate, 0.05% methylene blue and 0.165%
      parabens) and individual components were challenged against gram-positive and
      gram-negative organisms and fungi. Control solutions were heparin with
      preservatives. Studies included evaluation of eradication of planktonic bacteria
      and sessile organisms in a biofilm grown on polymeric and glass coupons. Biofilm
      samples were inspected by scanning electron microscopy, atomic force microscopy
      and vital stains. RESULTS: The C/MB/P solution, contrary to heparin, kills most
      tested planktonic microorganisms within 1 h of incubation. All tested organisms
      have an MIC of 25% or less of the original concentration of a new catheter lock.
      Bacteria strains did not develop resistance over more than 40 passages of culture
      suspensions. The C/MB/P solution is able to kill nearly all sessile bacteria in
      biofilm growth on plastic or glass discs in 1 h. Microscopic methods demonstrated
      extensive physical elimination of biofilm deposits from treated coupons. In
      contrast, heparin had a minimal effect on planktonic or biofilm organisms.
      CONCLUSIONS: The new multicomponent lock solution has strong antimicrobial
      properties against both planktonic and sessile microorganisms. By comparison,
      heparin with preservative has weak antibacterial properties against planktonic
      and biofilm bacteria. The tested catheter lock may have usefulness in preventing
      bacterial colonization of haemodialysis catheters and diminishing the incidence
      of catheter-related bacteraemia.

PMID- 19181763
TI  - Nonruminant nutrition symposium on mineral absorption: what is known?

PMID- 19181764
TI  - Influence of early postweaning traits on genetic improvement of meat productivity
      in purebred Berkshire pigs.
AB  - The objective of this study was to estimate genetic parameters for growth and
      body composition traits at 60 d of age and at finish in a population of Berkshire
      pigs and to evaluate the effectiveness of selection at 60 d of age for meat
      productivity. A total of 4,548 purebred Berkshire (2,344 males and 2,204 females)
      pigs born between December 1994 and January 2005 were used in this study. The
      traits analyzed were BW at 60 d of age; daily BW gain from birth to finish, from
      weaning to 60 d, from weaning to finish, and from 60 d to finish; age at finish;
      backfat thickness at 60 d of age and at finish; loin eye area at 60 d of age
      (LEA60) and at finish; and the number of teats. The heritability estimates for BW
      at 60 d of age, daily BW gain from weaning to 60 d, backfat thickness at 60 d of
      age, and LEA60 were 0.22, 0.25, 0.49, and 0.22, respectively. The estimated
      common environmental effect for BW at 60 d of age, daily BW gain from weaning to
      60 d, backfat thickness at 60 d of age, and LEA60 were 0.12, 0.13, 0.18, and
      0.21, respectively. Therefore, the common environmental effect should be included
      in the model to analyze traits at 60 d of age. The positive genetic correlation
      between LEA60 and loin eye area at finish and the negative genetic correlation
      between LEA60 and backfat thickness at finish indicated that improvement of the
      ultrasonic loin eye area at 60 d of age may result in favorable correlated
      responses to the traits at finish, an increase in loin eye area, and a decrease
      in backfat thickness. In addition, genetic correlations of backfat thickness at
      60 d of age with backfat thickness at finish and loin eye area at finish were
      found to be favorable, indicating that improvement of ultrasonic backfat
      thickness at 60 d of age may result in greater correlated responses to the traits
      at finish: an increase in loin eye area and a decrease in backfat thickness.
      Therefore, constructing a selection scheme that includes body composition traits
      at 60 d and traits at finish is practical for gaining a greater selection
      response.

PMID- 19181765
TI  - Effect of ractopamine-hydrochloride on the fiber type distribution and shelf-life
      of six muscles of steers.
AB  - The goal of this study was to evaluate the effects of ractopamine-hydrochloride
      (RAC) supplementation on the myosin heavy chain isoform distribution and shelf
      life properties of muscles from beef top round, knuckle, and loin. Thirty-four
      steer carcasses were selected from 4 separate slaughter groups. Within each
      slaughter group (3 groups, n = 8; 1 group, n = 10), steers were separated into
      pens (n = 8) and fed 0 or 200 mg x animal(-1) x d(-1) of RAC for the final 28 d
      of feeding. Seventy-two hours postmortem, the longissimus lumborum,
      semimembranosus (SM), adductor, gracilis, vastus lateralis (VL), and rectus
      femoris were removed from each carcass. A subsample of each muscle was collected
      for immunohistochemical analysis. Whole muscles were vacuum packaged and wet aged
      at 1 +/- 2 degrees C for 13 d before processing into steaks for a 5-d simulated
      retail display study. Daily, steaks were analyzed for reduction of nitric oxide
      metmyoglobin, lean color, fat color, and surface discoloration. Objective
      measures of metmyoglobin, oxymyoglobin, L*, a*, and b* values were recorded
      daily. Ractopamine significantly (P < 0.05) changed the fiber type isoform
      distribution in all muscles except the SM. The VL and gracilis presented the
      greatest fiber type switch with approximately 21% of type I fibers switching to
      type IIA fibers. However, the fiber type shifts induced by RAC supplementation
      had little to no effect on subjective and objective color measurements during the
      5-d retail display period. Metmyoglobin and oxymyoglobin accumulation, L*, a*,
      and b*-values were not affected (P > 0.05) by RAC supplementation. Percent nitric
      oxide metmyoglobin reduction data indicate that reducing ability of RAC-treated
      steaks from the adductor and longissimus lumborum were significantly affected (P
      < 0.05). Visual panel data suggest that RAC tended (P < 0.10) to have the most
      detrimental effect on the lean color and surface discoloration scores of steaks
      from the VL during the last 3 d of display. Ractopamine significantly (P < 0.05)
      increased the surface discoloration of the rectus femoris and SM on d 5. Although
      RAC supplementation had no effect on objective color measurements, subjective
      measurements indicate that it may have some effect on surface discoloration of
      some muscles.

PMID- 19181766
TI  - The influence of dietary selenium on common indicators of selenium status and
      liver glutathione peroxidase-1 messenger ribonucleic acid.
AB  - The objective of this research was to determine the influence of dietary Se on
      various indicators of Se status and relative liver glutathione peroxidase 1 (GPx
      1) messenger RNA (mRNA) levels in growing Holstein bull calves. Calves (n = 14,
      7/diet) were started 28 d after birth on a Se-adequate (SeA) or Se-deficient diet
      (SeD) and maintained on the diet until 180 d of age. Blood samples were taken
      from each calf for determination of erythrocyte GPx-1 and plasma GPx-3 activities
      and plasma Se concentration on d 28 of age, every 28 d thereafter, and at 180 d
      of age. To assess liver Se and GPx-1 mRNA, 3 calves were first killed at d 21 of
      age for baseline (BSL) measurements, and 4 calves from each treatment were killed
      at trial conclusion. Feed intake and ADG were not affected (P = 0.62) by dietary
      Se concentrations. However, liver Se concentration was greater (P < 0.05) for BSL
      calves and SeA calves than SeD calves, but no difference (P = 0.68) was observed
      between BSL calves and SeA calves. Plasma Se was greater for SeA calves (P <
      0.01) than for SeD calves by d 56 of age. The GPx-1 activity was greater in SeA
      calves (P < 0.01) by d 84 of age, whereas GPx-3 activity was greater in SeA
      calves, but not until d 180 of age (P < 0.01). There was a 50% decrease in GPx-1
      mRNA for the SeD calves (P < 0.05) compared with SeA calves. Thus, relative GPx-1
      mRNA transcript level is reflective of Se status in the bovine. Furthermore, 152
      d on a semi-purified, SeD diet is adequate to create a Se deficiency in growing
      Holstein bull calves started on a SeD diet at 28 d of age.

PMID- 19181767
TI  - Evaluation of modeling procedure for fitting in situ feed degradation profiles.
AB  - In situ degradation of feeds is a common methodology used for describing the
      digestion rate and potential for many chemical components of ruminant feedstuffs.
      The inferences involving the parameters of these procedures may be of
      questionable accuracy and precision because nonlinear regression techniques that
      are employed to fit these models do not produce unbiased, normally distributed,
      and minimum variance parameter estimates until the sample size becomes very
      large. Therefore, the objective of this experiment was to determine the accuracy
      and precision of parameter estimates determined by a 2-stage approach (TS; in
      which individual kinetic parameter estimates are obtained in the first stage and
      population estimates are obtained by arithmetic mean in the second), a 2-stage,
      geometric mean approach (GEO), and by nonlinear mixed modeling (NLMM) using
      simulation techniques. An experiment using corn silage NDF was used as a
      reference for simulating parameter and error structures. For all analyses, 500
      experiments were simulated with sampling time points of 1, 2, 4, 8, 16, 24, 48,
      and 72 h. Increasing levels of animal and bag replication were evaluated at 2
      levels of residual variability [residual SD of 2.95 (observed from the data; R(2)
      = 0.985) and 5.90 (2x observed; R(2) = 0.950)]. Evaluation of the first-order
      exponential model with discrete lag revealed that median bias of TS and GEO
      parameter estimates were more sensitive to increased residual variation and
      degree of replication than NLMM. When residual variation was less, precision of
      parameter estimates was less affected by estimation procedure; when residual
      variation was greater, precision of parameter estimates was generally improved by
      NLMM. From the results of this experiment it is concluded that, in most cases,
      NLMM is equal or better than TS or GEO from the perspective of minimizing bias
      and maximizing precision of parameter estimates.

PMID- 19181768
TI  - Milk leptin in sows and blood leptin and growth of their offspring.
AB  - Twenty-one mixed-parity (average 2.4 +/- 0.49) crossbred sows and their offspring
      were used to determine whether sow milk leptin at farrowing was related to
      neonatal serum leptin and pig growth to weaning. During farrowing, pigs were
      randomly allotted to suckling (n = 99) or delayed suckling (n = 89) groups, with
      delayed suckling pigs placed in a group pen apart from the dam before suckling.
      Both groups had access to heat lamps. Colostrum samples were collected no more
      than 2 h after farrowing the first pig. Blood samples were collected from all
      pigs approximately 2 h after farrowing was complete; pigs were then ear notched
      and returned to their dams. Pig BW was recorded at 1.2 +/- 0.04 d of age and
      again at weaning. Milk and blood serum were collected after centrifugation;
      leptin concentrations were estimated using RIA. Leptin was detected in colostral
      milk, as expected, and averaged 46.0 +/- 1.1 ng/mL. Pig serum leptin (P < 0.02)
      was greater in suckling pigs than in delayed suckling pigs, averaging 0.69 +/-
      0.08 and 0.54 +/- 0.07 ng/mL, respectively. Although male pigs were heavier (P <
      0.01) at birth than female pigs (1,507 +/- 52 vs. 1,381 +/- 43 g), ADG to weaning
      and weaning weights were similar for both sexes, averaging 229 +/- 14 g and 5,829
      +/- 323 g, respectively, for all pigs; serum leptin concentrations were not
      affected by sex of the pig. Milk serum leptin was not associated with litter
      size, parity, pig birth weight, ADG to weaning, or weaning weight. Suckling
      status did not influence ADG to weaning or weaning weight of pigs; neonatal pig
      serum leptin was not related to birth weight, weaning weight, or ADG to weaning.
      These results indicate that leptin is not directly related to early neonatal
      growth in the pig; however, more in-depth studies are needed to determine
      possible indirect or long-term effects of early leptin exposure.

PMID- 19181769
TI  - Difference in severity of porcine circovirus type two-induced pathological
      lesions between Landrace and Pietrain pigs.
AB  - Anecdotal information from the field suggests that there are host genetic
      differences in susceptibility to porcine circovirus type 2 (PCV2) associated
      disease among Landrace and Pietrain breeds. The objective of this study was to
      determine if a difference exists in PCV2 susceptibility between Landrace and
      Pietrain pigs under experimental conditions. Thirty-nine Landrace pigs and 39
      Pietrain pigs were blocked by breed, sire, dam, and litter and randomly divided
      into the following 4 groups: Landrace noninoculated negative control (Landrace
      NEG; n = 13), Pietrain noninoculated negative control (Pietrain-NEG; n = 13),
      Landrace-PCV2 (n = 26; Landrace), and Pietrain-PCV2 (n = 26; Pietrain). After
      waning of passively acquired anti-PCV2 antibodies, Landrace-PCV2 and Pietrain
      PCV2 groups were inoculated with PCV2 isolate ISU-40895. The Landrace-NEG and
      Pietrain-NEG groups were housed in a separate room, remained noninoculated, and
      served as negative controls. All pigs in all groups were necropsied at 21 d post
      PCV2-inoculation. Onset of seroconversion and concentrations of anti-PCV2-IgM,
      anti-PCV2-IgG, and anti-PCV2 neutralizing antibodies were similar in Landrace
      PCV2 and Pietrain-PCV2 groups. Furthermore, the amount of PCV2 DNA and cytokine
      concentrations in serum and plasma samples were not different between the 2 PCV2
      inoculated groups. The severity of PCV2-associated microscopic lesions was
      different between Landrace and Pietrain pigs; Landrace-PCV2 pigs had
      significantly (P < 0.05) more severe lymphoid lesions than the Pietrain-PCV2
      pigs. Although the pigs originated from the same farm where their dams were
      commingled, passively acquired anti-PCV2-antibodies waned in Pietrain pigs by
      approximately 12 wk of age, whereas the majority of the Landrace pigs remained
      PCV2 seropositive until 18 wk of age and beyond. The results from this study
      indicate that a genetic difference exists between these 2 breeds of pigs in
      susceptibility to PCV2-associated lesions.

PMID- 19181770
TI  - An evaluation of bovine respiratory disease complex in feedlot cattle: Impact on
      performance and carcass traits using treatment records and lung lesion scores.
AB  - The objective of this study was to investigate the effects of bovine respiratory
      disease (BRD) complex on economically important production traits with the use of
      health records in combination with lung lesion scores obtained at slaughter.
      Records from 5,976 animals were used in this study from cattle that were managed
      in Midwestern feedlots. Average daily gain for 3 different feeding periods
      (acclimation, on-test, and overall test) along with final BW were evaluated as
      performance measures. Hot carcass weight, LM area, subcutaneous fat cover, and
      marbling score were collected at slaughter. All calves were monitored by
      experienced feedlot personnel and treated according to the specific health
      protocol of each feedlot. Incidence of BRD was observed at a rate of 8.17%, and
      lung lesions at slaughter were present in 61.9% of cattle from a subpopulation (n
      = 1,665). From this group of cattle, the overall incidence of BRD, which was
      defined as cattle that had lung lesions, that were treated for BRD in the
      feedlot, or both, was 64.4%. Incidence of BRD in the feedlot decreased ADG during
      both the acclimation period (0.37 +/- 0.03 kg) and the overall test period (0.07
      +/- 0.01 kg). Incidence of BRD also had significant effects on HCW and marbling
      score with reduction of 8.16 +/- 1.38 kg and 0.13 +/- 0.04, respectively, in
      treated cattle. The adverse effects on production traits tended to increase as
      the number of treatments increased. Potential decrease in performance and carcass
      merit observed in this study were associated with a decline of $23.23, $30.15,
      and $54.01 in carcass value when comparing cattle never treated with cattle
      treated once, twice, or 3 or more times, respectively. The presence of lung
      lesions did not have a significant effect on any of the traits; however, there
      was an association between the presence of active bronchial lymph nodes and less
      productivity of feedlot cattle.

PMID- 19181771
TI  - Quantification of factors affecting semen traits in artificial insemination boars
      from animal model analyses.
AB  - The objective of this study was to investigate individual fixed effects in an
      animal model for breeding value estimation for semen traits of pig sire breeds.
      Data (151,755 ejaculates collected from 2000 through 2007 from 2,077 Duroc, sire
      line of Large White, Pietrain, and single cross boars between these breeds) were
      from 20 AI centers in the Czech Republic. Traits considered per ejaculate were
      semen volume, sperm concentration, motility, percentage of abnormal sperm, total
      number of sperm, and number of functional sperm. Fixed effects in the animal
      model were month of collection, age of the boar at collection, interval between
      subsequent collections, combined effect of AI center and year, and breed or
      crossbred combination. Semen volume was greatest from October through December
      and was least in March and April. Sperm concentration was greatest in winter and
      early spring and least in late summer and early autumn. Both total sperm number
      and number of functional sperm were greatest in winter and least in summer. Semen
      volume increased until about 2 yr of age and remained relatively constant
      thereafter. Sperm concentration increased sharply until 11 mo of age, followed by
      a long-term moderate decrease until 3 yr of age and stabilization thereafter.
      Motility decreased steadily with age, whereas the percentage of abnormal sperm
      increased over the entire productive lifetime of the boar. There were initial
      steep increases with advancing age in total sperm number and number of functional
      sperm, both reaching their maxima at about 2 yr of age and then dropping slightly
      to the end of the time scale investigated. The interval between subsequent
      collections had a large effect on sperm concentration. Motility tended to
      decrease and the percentage of abnormal sperm tended to increase with lengthening
      time interval between collections. Both total sperm number and number of
      functional sperm rose as the interval between collections increased to 10 d.
      Although boars will continue to be selected mainly for their breeding values for
      production and female reproduction traits, AI centers should also place
      economically optimal emphasis on boars with favorable estimated breeding values
      for semen traits.

PMID- 19181772
TI  - Clinical and pathological responses of pigs from two genetically diverse
      commercial lines to porcine reproductive and respiratory syndrome virus
      infection.
AB  - The response to infection from porcine reproductive and respiratory syndrome
      virus (PRRSV) for 2 genetically diverse commercial pig lines was investigated.
      Seventy-two pigs from each line, aged 6 wk, were challenged with PRRSV VR-2385,
      and 66 litter-mates served as control. The clinical response to infection was
      monitored throughout the study and pigs were necropsied at 10 or 21 d
      postinfection. Previous analyses showed significant line differences in
      susceptibility to PRRSV infection. This study also revealed significant line
      differences in growth during infection. Line B, characterized by faster growth
      rate than line A in the absence of infection, suffered more severe clinical
      disease and greater reduction in BW growth after infection. Correlations between
      growth and disease-related traits were generally negative, albeit weak.
      Correlations were also weak among most clinical and pathological traits. Clinical
      disease traits such as respiratory scores and rectal temperatures were poor
      indicators of virus levels, pathological damage, or growth during PRRSV
      infection. Relationships between traits varied over time, indicating that
      different disease-related mechanisms may operate at different time scales and,
      therefore, that the time of assessing host responses may influence the
      conclusions drawn about biological significance. Three possible mechanisms
      underlying growth under PRRSV infection were proposed based on evidence from this
      and previous studies. It was concluded that a comprehensive framework describing
      the interaction between the biological mechanisms and the genetic influence on
      these would be desirable for achieving progress in the genetic control of this
      economically important disease.

PMID- 19181773
TI  - Characterization of tumefactive demyelinating lesions using MR imaging and in
      vivo proton MR spectroscopy.
AB  - BACKGROUND AND OBJECTIVES: Diagnosis of tumefactive demyelinating lesions (TDLs)
      is challenging to both clinicians and radiologists. Our objective in this study
      was to analyze and characterize these lesions clinically, biochemically,
      electrophysiologically, and on imaging. METHODS: A retrospective analysis with
      prospective follow-up of 18 cases of TDLs was performed. Imaging included T2-, T1
      weighted, fluid-attenuated inversion recovery (FLAIR), post-contrast T1-weighted,
      diffusion weighted imaging (DWI), and proton magnetic resonance spectroscopy
      (PMRS). RESULTS: All the lesions appeared hyperintense on T2 and FLAIR images.
      Increased Apparent diffusion coefficient (ADC) (0.93-2.21 x 10(-3) mm(2)/s) in
      centre of the lesion was seen in 14/18 cases; however, peripheral restriction
      (ADC values 0.55-0.64 x 10(-3) mm(2)/s) was noted in 11/18 cases. In all, 13/18
      cases showed contrast enhancement with open ring (n = 5), complete ring (n = 1),
      minimal (n = 4), and infiltrative (n = 3) pattern of enhancement. Nine of these
      13 cases also showed venular enhancement. On PMRS, nine showed
      glutamate/glutamine (Glx) at 2.4 ppm. CONCLUSION: Clinical features along with
      several MRI characteristics such as open ring enhancement, peripheral restriction
      on DWI, venular enhancement, and presence of Glx on spectroscopy may be rewarding
      in differentiating TDLs from neoplastic lesions.

PMID- 19181774
TI  - Earlier disability of the patients followed in Multiple Sclerosis centers
      compared to outpatients.
AB  - OBJECTIVE: The currently published works regarding the multiple sclerosis (MS)
      natural history report data were collected most often on population of patients
      recruited in MS centers. The aim was to compare the natural history of a
      population of patients followed in a MS centre (MSC) with patients followed
      outside a MS centre (NMSC). METHODS: Cases were identified through the LORSEP
      cohort, a network of neurologists (private ambulatory practice, hospitals, and MS
      centers) in France. RESULTS: A total of 3602 patients had been analyzed: 1036 MSC
      patients and 2566 NMSC patients. No difference was observed regarding gender and
      initial symptoms. Conversely, MSC patients were younger at MS onset and were more
      likely to have a primary progressive initial form. Median times (years) to the
      EDSS scores of 3, 4, and 6 were 5.8 (5.0-6.8), 8.4 (7.9-9.0), 16.0 (14.8-18.1) in
      the MSC group, respectively, whereas corresponding times were 8.4 (7.9-9.0), 12.3
      (11.4-13.4), 19.1 (18.0-20.2) in the NMSC group. These differences according to
      the type of MS supervision were statistically significant for EDSS3 (P < 0.0001),
      EDSS4 (P < 0.0001), and EDSS6 (P = 0.01), respectively. These findings were
      confirmed in Cox multivariate models. CONCLUSIONS: The patients followed in a MS
      centre had earlier disability than patients managed otherwise. Analyses
      exclusively conducted in patients with MS supervised in specialized centers may
      falsely misestimate the times needed to reach major disability landmarks. Before
      using registries to study the natural history of MS, efforts should be performed
      to verify in how far data are exhaustive and to understand the local health care
      system.

PMID- 19181775
TI  - Longitudinal correlates of fatigue in multiple sclerosis.
AB  - OBJECTIVE: To determine the predictors of longitudinal changes in fatigue based
      on pain, mood, and neurological impairment across multiple sclerosis (MS)
      subtypes. BACKGROUND: Fatigue is the most common symptom of MS but remains poorly
      understood. The New York State Multiple Sclerosis Consortium (NYSMSC) database
      offers a unique opportunity to longitudinally assess a variety of potential
      fatigue correlates in a very large and diverse MS sample. DESIGN/METHODS: This
      study examined baseline and 1-year follow-up data on 2768 patients drawn from the
      NYSMSC database regarding fatigability, pain, depressive symptoms, MS subtype,
      and expanded disability status scale (EDSS). Correlates and predictors of fatigue
      were assessed in correlational and multiple regression analyses. RESULTS:
      Baseline fatigue, pain, and depression accounted for 34.6% of the variance in 1
      year follow-up fatigue scores. Fatigue was lower in relapsing-remitting subjects
      than in other MS subtypes. Fatigue consistently correlated at baseline and follow
      up with depressive symptoms, pain severity, and EDSS. Changes in fatigue
      correlated with changes in other variables. CONCLUSIONS: Predictors of fatigue at
      1 year include baseline fatigue, pain, mood, and EDSS. These symptoms are also
      correlated at baseline, follow-up, and in change scores. Identifying predictors
      of fatigue may facilitate patient management.

PMID- 19181777
TI  - Test-retest reliability of the PRIME-MD: limitations in diagnosing mental
      disorders in primary care.
AB  - BACKGROUND: The primary care evaluation of mental disorders (PRIME-MD) can be
      seen as characteristic for successive refinements of criteria and structured
      interview techniques for diagnosing psychiatric disorders in primary care. It is
      one of the most widely used instruments, but there is no evidence to support its
      test-retest reliability. METHODS: With 1-week intervals between interviews, a
      test-retest study of the PRIME-MD was conducted in a general practice population
      of 100 distressed patients (20- to 60-years old) who were on sick leave. RESULTS:
      Almost everyone (89%) received one or more diagnoses at both measurements, and
      there was fair total agreement (kappa = 0.27). The best agreement was found for
      more severe threshold disorders [major depressive disorder (kappa = 0.58),
      dysthymia (kappa = 0.57), and generalized anxiety disorder (kappa = 0.59)], while
      we found indefinite results for the sub-threshold disorders [anxiety disorder not
      otherwise specified (NOS) (kappa =.30), minor depressive disorder (kappa = 
      0.03), and somatoform disorder NOS (kappa = 0.11)]. CONCLUSION: The PRIME-MD is
      one of the few instruments in primary care that actually diagnoses specific
      mental disorders according to the DSM criteria. However, there was a failure to
      adequately classify sub-threshold disorders. Mental disorders, as seen in primary
      care, encompass important specific symptoms and clinical syndromes that vary in
      duration and severity over time, but they also encompass an admixture of somatic
      and psychological symptoms that do not match current diagnostic systems. This
      most likely resulted in methodological uncertainty about the level of agreement.
      Diagnostic criteria in psychiatry need to be operationalized for use in primary
      care and require further evaluation.

PMID- 19181778
TI  - The response to lenalidomide of myelodysplastic syndrome patients with deletion
      del(5q) can be sequentially monitored in CD34+ progenitor cells.

PMID- 19181779
TI  - Green fluorescent protein transgene driven by Kit regulatory sequences is
      expressed in hematopoietic stem cells.
AB  - BACKGROUND: The transcriptional regulation of stem cell genes is still poorly
      understood. Kit, encoding the stem cell factor receptor, is a pivotal molecule
      for multiple types of stem/progenitor cells. We previously generated mouse lines
      expressing transgenic green fluorescent protein under the control of Kit
      promoter/first intron regulatory elements, and we demonstrated expression in
      hematopoietic progenitors. DESIGN AND METHODS: In the present work we
      investigated whether the transgene is also expressed in hematopoietic stem cells
      of adult bone marrow and fetal liver. To this purpose, we tested, in long-term
      repopulating assays, cell fractions expressing different levels of green
      fluorescent protein within Kit-positive or SLAM-selected populations. RESULTS:
      The experiments demonstrated transgene expression in both fetal and adult
      hematopoietic stem cells and indicated that the transgene is transcribed at
      distinctly lower levels in hematopoietic stem cells than in pluripotent and
      committed progenitors. CONCLUSIONS: These results, together with previous data,
      show that a limited subset of DNA sequences drives gene expression in number of
      stem cell types (hematopoietic stem cells, primordial germ cells, cardiac stem
      cells). Additionally, our results might help to further improve high level
      purification of hematopoietic stem cells for experimental purposes. Finally, as
      the Kit/green fluorescent protein transgene is expressed in multiple stem cell
      types, our transgenic model provides powerful in vivo system to track these cells
      during development and tissue regeneration.

PMID- 19181780
TI  - Increased CD4+ and CD8+ effector memory T cells in patients with aplastic anemia.

PMID- 19181783
TI  - In HPA 1a-immunized women the decrease in anti-HPA 1a antibody level during
      pregnancy is not associated with anti-idiotypic antibodies.

PMID- 19181784
TI  - A JAK2-V617F activating mutation in addition to KIT and FLT3 mutations is
      associated with clinical outcome in patients with t(8;21)(q22;q22) acute myeloid
      leukemia.

PMID- 19181781
TI  - Molecular basis of inherited microcytic anemia due to defects in iron acquisition
      or heme synthesis.
AB  - Microcytic anemia is the most commonly encountered anemia in general medical
      practice. Nutritional iron deficiency and beta thalassemia trait are the primary
      causes in pediatrics, whereas bleeding disorders and anemia of chronic disease
      are common in adulthood. Microcytic hypochromic anemia can result from a defect
      in globin genes, in heme synthesis, in iron availability or in iron acquisition
      by the erythroid precursors. These microcytic anemia can be sideroblastic or not,
      a trait which reflects the implications of different gene abnormalities. Iron is
      a trace element that may act as a redox component and therefore is integral to
      vital biological processes that require the transfer of electrons as in oxygen
      transport, oxidative phosphorylation, DNA biosynthesis and xenobiotic metabolism.
      However, it can also be pro-oxidant and to avoid its toxicity, iron metabolism is
      strictly controlled and failure of these control systems could induce iron
      overload or iron deficient anemia. During the past few years, several new
      discoveries mostly arising from human patients or mouse models have highlighted
      the implication of iron metabolism components in hereditary microcytic anemia,
      from intestinal absorption to its final inclusion into heme. In this paper we
      will review the new information available on the iron acquisition pathway by
      developing erythrocytes and its regulation, and we will consider only inherited
      microcytosis due to heme synthesis or to iron metabolism defects. This
      information could be useful in the diagnosis and classification of these
      microcytic anemias.

PMID- 19181785
TI  - Myelofibrotic transformation in essential thrombocythemia.

PMID- 19181786
TI  - Treatment of severe aplastic anemia with a combination of horse antithymocyte
      globulin and cyclosporine, with or without sirolimus: a prospective randomized
      study.
AB  - BACKGROUND: We hypothesized that the addition of sirolimus to standard horse
      antithymocyte globulin (h-ATG) and cyclosporine (CsA) would improve response
      rates in severe aplastic anemia, due to its complementary and synergistic
      properties to cyclosporine A. DESIGN AND METHODS: To test this hypothesis, we
      conducted a prospective randomized study comparing hATG/CsA/sirolimus to standard
      h-ATG/CsA. A total of 77 patients were treated from June 2003 to November 2005;
      35 received h-ATG/CsA/sirolimus and 42 h-ATG/CsA. The two groups were well
      matched demographically and in blood counts prior to therapy. The primary end
      point was hematologic response rate at 3 months, defined as no longer meeting the
      criteria for severe aplastic anemia. The study was powered to show a superior
      hematologic response rate of h-ATG/CsA/sirolimus compared to standard h-ATG/CsA.
      RESULTS: The overall response rate at 3 months was 37% for h-ATG/CsA/sirolimus
      and 50% for h-ATG/CsA and at 6 months 51% for h-ATG/CsA/sirolimus and 62% for h
      ATG/CsA. After a planned interim analysis of 30 evaluable patients in each arm,
      accrual to the h-ATG/CsA/sirolimus arm was closed, as the conditional power for
      rejecting the null hypothesis was less than 1%. The rate of relapse, clonal
      evolution, and survival (secondary outcomes) did not differ significantly between
      patients treated with the two different regimens. CONCLUSIONS: Despite a
      theoretical rationale for its use, sirolimus did not improve the response rate in
      patients with severe aplastic anemia when compared to standard h-ATG/CsA.

PMID- 19181787
TI  - Malarial anemia and STAT6.

PMID- 19181788
TI  - T-cell acute lymphoblastic leukemia.

PMID- 19181789
TI  - Changing paradigms in the treatment of multiple myeloma.

PMID- 19181790
TI  - Inherited thrombotic thrombocytopenic purpura.

PMID- 19181791
TI  - Hepatitis C virus and allogeneic stem cell transplantation still matters!

PMID- 19181792
TI  - Cryptochrome-1 expression: a new prognostic marker in B-cell chronic lymphocytic
      leukemia.
AB  - Chronic lymphocytic leukemia is an adult-onset leukemia with a heterogeneous
      clinical behavior. When chronic lymphocytic leukemia cases were divided on the
      basis of IgV(H) mutational status, widely differing clinical courses were
      revealed. Since IgV(H) sequencing is difficult to perform in a routine diagnostic
      laboratory, finding a surrogate for IgV(H) mutational status seems an important
      priority. In the present study, we proposed the use of Cryptochrome-1 as a new
      prognostic marker in early-stage chronic lymphocytic leukemia. Seventy patients
      (Binet stage A, without treatment) were included in the study. We correlated
      Cryptochrome-1 mRNA with well established prognostic markers such as IgV(H)
      mutations, ZAP70, LPL or CD38 expression and chromosomal abnormalities. High
      Cryptochrome-1 expression correlated with IgV(H) unmutated samples. In addition,
      Cryptochrome-1 was a valuable predictor of disease progression in early-stage
      chronic lymphocytic leukemia, therefore it can be introduced in clinical practice
      with the advantage of a simplified method of quantification.

PMID- 19181793
TI  - Late relapse of acute myeloid leukemia with mutated NPM1 after eight years:
      evidence of NPM1 mutation stability.

PMID- 19181795
TI  - The putrescine Importer PuuP of Escherichia coli K-12.
AB  - The Puu pathway is a putrescine utilization pathway involving gamma-glutamyl
      intermediates. The genes encoding the enzymes of the Puu pathway form a gene
      cluster, the puu gene cluster, and puuP is one of the genes in this cluster. In
      Escherichia coli, three putrescine importers, PotFGHI, PotABCD, and PotE, were
      discovered in the 1990s and have been studied; however, PuuP had not been
      discovered previously. This paper shows that PuuP is a novel putrescine importer
      whose kinetic parameters are equivalent to those of the polyamine importers
      discovered previously. A puuP(+) strain absorbed up to 5 mM putrescine from the
      medium, but a DeltapuuP strain did not. E. coli strain MA261 has been used in
      previous studies of polyamine transporters, but PuuP had not been identified
      previously. It was revealed that the puuP gene of MA261 was inactivated by a
      point mutation. When E. coli was grown on minimal medium supplemented with
      putrescine as the sole carbon or nitrogen source, only PuuP among the polyamine
      importers was required. puuP was expressed strongly when putrescine was added to
      the medium or when the puuR gene, which encodes a putative repressor, was
      deleted. When E. coli was grown in M9-tryptone medium, PuuP was expressed mainly
      in the exponential growth phase, and PotFGHI was expressed independently of the
      growth phase.

PMID- 19181796
TI  - Identification of the polyketide synthase involved in the biosynthesis of the
      surface-exposed lipooligosaccharides in mycobacteria.
AB  - Lipooligosaccharides (LOS) are highly antigenic glycolipids produced by a number
      of Mycobacterium species, which include "M. canettii," a member of the M.
      tuberculosis complex, and the opportunistic pathogens M. marinum and M. kansasii.
      The various LOS share a core composed of trehalose esterified by at least 1 mole
      of polymethyl-branched fatty acid (PMB-FA) and differ from one another by their
      oligosaccharide extensions. In this study, we identified a cluster of genes,
      MSMEG_4727 through MSMEG_4741, likely involved in the synthesis of LOS in M.
      smegmatis. Disruption of MSMEG_4727 (the ortholog of pks5 of M. tuberculosis),
      which encodes a putative polyketide synthase, resulted in the concomitant
      abrogation of the production of both PMB-FA and LOS in the mutant strain.
      Complementation of the mutant with the wild-type gene fully restored the
      phenotype. We also showed that, in contrast to the case for "M. canettii" and M.
      marinum, LOS are located in deeper compartments of the cell envelope of M.
      smegmatis. The availability of two mycobacterial strains differing only in LOS
      production should help in defining the biological role(s) of this important
      glycolipid.

PMID- 19181797
TI  - The Rv1712 Locus from Mycobacterium tuberculosis H37Rv codes for a functional CMP
      kinase that preferentially phosphorylates dCMP.
AB  - The Mycobacterium tuberculosis cmk gene, predicted to encode a CMP kinase (CMK),
      was cloned and expressed, and its product was purified to homogeneity. Steady
      state kinetics confirmed that M. tuberculosis CMK is a monomer that
      preferentially phosphorylates CMP and dCMP by a sequential mechanism. A plausible
      role for CMK is discussed.

PMID- 19181798
TI  - Regulation of the mazEF toxin-antitoxin module in Staphylococcus aureus and its
      impact on sigB expression.
AB  - In Staphylococcus aureus, the sigB operon codes for the alternative sigma factor
      sigma(B) and its regulators that enable the bacteria to rapidly respond to
      environmental stresses via redirection of transcriptional priorities. However, a
      full model of sigma(B) regulation in S. aureus has not yet emerged. Earlier data
      has suggested that mazEF, a toxin-antitoxin (TA) module immediately upstream of
      the sigB operon, was transcribed with the sigB operon. Here we demonstrate that
      the promoter P(mazE) upstream of mazEF is essential for full sigma(B) activity
      and that instead of utilizing autorepression typical of TA systems, sigB
      downregulates this promoter, providing a negative-feedback loop for sigB to
      repress its own transcription. We have also found that the transcriptional
      regulator SarA binds and activates P(mazE). In addition, P(mazE) was shown to
      respond to environmental and antibiotic stresses in a way that provides an
      additional layer of control over sigB expression. The antibiotic response also
      appears to occur in two other TA systems in S. aureus, indicating a shared
      mechanism of regulation.

PMID- 19181799
TI  - Pathway of gamma-aminobutyrate metabolism in Rhizobium leguminosarum 3841 and its
      role in symbiosis.
AB  - Pea plants incubated in 15N2 rapidly accumulated labeled gamma-aminobutyrate
      (GABA) in the plant cytosol and in bacteroids of Rhizobium leguminosarum bv.
      viciae 3841. Two pathways of GABA metabolism were identified in R. leguminosarum
      3841. In the first, glutamate is formed by GABA aminotransferase (GabT),
      transferring the amino group from GABA to 2-oxoglutarate. In the second, alanine
      is formed by two omega-aminotransferases (OpaA and OpaB), transferring the amino
      group from GABA to pyruvate. While the gabT mutant and the gabT opaA double
      mutant grew on GABA as a nitrogen source, the final triple mutant did not. The
      semialdehyde released from GABA by transamination is oxidized by succinate
      semialdehyde dehydrogenase (GabD). Five of six potential GabD proteins in R.
      leguminosarum bv. viciae 3841 (GabD1, -D2, -D3, -D4, and -D5) were shown by
      expression analysis to have this activity. However, only mutations of GabD1,
      GabD2, and GabD4 were required to prevent utilization of GABA as the sole
      nitrogen source in culture. The specific enzyme activities of GabT, Opa, and GabD
      were highly elevated in bacteroids relative to cultured bacteria. This was due to
      elevated expression of gabT, opaA, gabD1, and gabD2 in nodules. Strains mutated
      in aminotransferase and succinate semialdehyde dehydrogenases (gabT, opaA, or
      opaB and gabD1, gabD2, or gabD4, respectively) that cannot use GABA in culture
      still fixed nitrogen on plants. While GABA catabolism alone is not essential for
      N2 fixation in bacteroids, it may have a role in energy generation and in
      bypassing the decarboxylating arm of the tricarboxylic acid cycle.

PMID- 19181801
TI  - YbeY, a heat shock protein involved in translation in Escherichia coli.
AB  - Here we provide evidence that YbeY, a conserved heat shock protein with unknown
      function, is involved in the translation process. ybeY deletion mutants are
      temperature sensitive and have a significantly reduced thermotolerance.
      Nonetheless, there appears to be no damage of the protein quality control of
      mature polypeptides, as the levels of chaperones and proteases are normal and
      there is no accumulation of aggregates. Rather, the mutation results in a
      significant reduction in the level of polysomes, and upon a shift to a
      restrictive temperature (42 degrees C), there is an immediate and severe slowdown
      of translation. Taken together, the data indicate that YbeY is an important
      factor for bacterial translation even at 37 degrees C but becomes essential at
      high temperatures.

PMID- 19181800
TI  - Conjugative transfer of the integrative conjugative elements ICESt1 and ICESt3
      from Streptococcus thermophilus.
AB  - Integrative and conjugative elements (ICEs), also called conjugative transposons,
      are genomic islands that excise, self-transfer by conjugation, and integrate in
      the genome of the recipient bacterium. The current investigation shows the
      intraspecies conjugative transfer of the first described ICEs in Streptococcus
      thermophilus, ICESt1 and ICESt3. Mitomycin C, a DNA-damaging agent, derepresses
      ICESt3 conjugative transfer almost 25-fold. The ICESt3 host range was determined
      using various members of the Firmicutes as recipients. Whereas numerous ICESt3
      transconjugants of Streptococcus pyogenes and Enterococcus faecalis were
      recovered, only one transconjugant of Lactococcus lactis was obtained. The newly
      incoming ICEs, except the one from L. lactis, are site-specifically integrated
      into the 3' end of the fda gene and are still able to excise in these
      transconjugants. Furthermore, ICESt3 was retransferred from E. faecalis to S.
      thermophilus. Recombinant plasmids carrying different parts of the ICESt1
      recombination module were used to show that the integrase gene is required for
      the site-specific integration and excision of the ICEs, whereas the excisionase
      gene is required for the site-specific excision only.

PMID- 19181802
TI  - Different biochemical mechanisms ensure network-wide balancing of reducing
      equivalents in microbial metabolism.
AB  - To sustain growth, the catabolic formation of the redox equivalent NADPH must be
      balanced with the anabolic demand. The mechanisms that ensure such network-wide
      balancing, however, are presently not understood. Based on 13C-detected
      intracellular fluxes, metabolite concentrations, and cofactor specificities for
      all relevant central metabolic enzymes, we have quantified catabolic NADPH
      production in Agrobacterium tumefaciens, Bacillus subtilis, Escherichia coli,
      Paracoccus versutus, Pseudomonas fluorescens, Rhodobacter sphaeroides,
      Sinorhizobium meliloti, and Zymomonas mobilis. For six species, the estimated
      NADPH production from glucose catabolism exceeded the requirements for biomass
      synthesis. Exceptions were P. fluorescens, with balanced rates, and E. coli, with
      insufficient catabolic production, in which about one-third of the NADPH is
      supplied via the membrane-bound transhydrogenase PntAB. P. versutus and B.
      subtilis were the only species that appear to rely on transhydrogenases for
      balancing NADPH overproduction during growth on glucose. In the other four
      species, the main but not exclusive redox-balancing mechanism appears to be the
      dual cofactor specificities of several catabolic enzymes and/or the existence of
      isoenzymes with distinct cofactor specificities, in particular glucose 6
      phosphate dehydrogenase. An unexpected key finding for all species, except E.
      coli and B. subtilis, was the lack of cofactor specificity in the oxidative
      pentose phosphate pathway, which contrasts with the textbook view of the pentose
      phosphate pathway dehydrogenases as being NADP+ dependent.

PMID- 19181803
TI  - Role of potassium uptake systems in Sinorhizobium meliloti osmoadaptation and
      symbiotic performance.
AB  - Stimulation of potassium uptake is the most rapid response to an osmotic upshock
      in bacteria. This cation accumulates by a number of different transport systems
      whose importance has not been previously addressed for rhizobia. In silico
      analyses reveal the presence of genes encoding four possible potassium uptake
      systems in the genome of Sinorhizobium meliloti 1021: Kup1, Kup2, Trk, and Kdp.
      The study of the relevance of these systems under a number of different growth
      conditions and in symbiosis showed that the integrity of Kup1 or Trk is essential
      for growth under laboratory conditions even in osmotically balanced media and the
      absence of both systems leads to a reduced infectivity and competitiveness of the
      bacteria in alfalfa roots. Trk is the main system involved in the accumulation of
      potassium after an osmotic upshift and the most important system for growth of S.
      meliloti under hyperosmotic conditions. The other three systems, especially Kup1,
      are also relevant during the osmotic adaptation of the cell, and the relative
      importance of the Kdp system increases at low potassium concentrations.

PMID- 19181804
TI  - In vitro characterization of the enzyme properties of the phospholipid N
      methyltransferase PmtA from Agrobacterium tumefaciens.
AB  - Agrobacterium tumefaciens requires phosphatidylcholine (PC) in its membranes for
      plant infection. The phospholipid N-methyltransferase PmtA catalyzes all three
      transmethylation reactions of phosphatidylethanolamine (PE) to PC via the
      intermediates monomethylphosphatidylethanolamine (MMPE) and
      dimethylphosphatidylethanolamine (DMPE). The enzyme uses S-adenosylmethionine
      (SAM) as the methyl donor, converting it to S-adenosylhomocysteine (SAH). Little
      is known about the activity of bacterial Pmt enzymes, since PC biosynthesis in
      prokaryotes is rare. In this article, we present the purification and in vitro
      characterization of A. tumefaciens PmtA, which is a monomeric protein. It binds
      to PE, the intermediates MMPE and DMPE, the end product PC, and
      phosphatidylglycerol (PG) and phosphatidylinositol. Binding of the phospholipid
      substrates precedes binding of SAM. We used a coupled in vitro assay system to
      demonstrate the enzymatic activity of PmtA and to show that PmtA is inhibited by
      the end products PC and SAH and the antibiotic sinefungin. The presence of PG
      stimulates PmtA activity. Our study provides insights into the catalysis and
      control of a bacterial phospholipid N-methyltransferase.

PMID- 19181805
TI  - Plasmid capture by the Bacillus thuringiensis conjugative plasmid pXO16.
AB  - Conjugation, mobilization, and retromobilization are three related mechanisms of
      horizontal gene transfer in bacteria. They have been extensively studied in gram
      negative species, where retromobilization, the capture of DNA from a recipient by
      a donor cell, was shown to result from two successive steps: the transfer of the
      conjugative plasmid from the donor to the recipient followed by the retrotransfer
      of the mobilizable plasmid to the donor. This successive model was established
      for gram-negative bacteria but was lacking experimental data from the gram
      positive counterparts. In the present work, the mobilization and
      retromobilization abilities of the conjugative plasmid pXO16 from Bacillus
      thuringiensis subsp. israelensis were studied using the mobilizable plasmids
      pUB110 and pE194 and the "nonmobilizable" element pC194 lacking the mob and oriT
      features (all from Staphylococcus aureus). Experimental data suggested a
      successive model, since different retromobilization frequencies were observed
      between the small plasmids. More importantly, retromobilization was shown to be
      delayed by 50 and 150 min for pUB110 and pE194, respectively, compared to pXO16
      conjugation. Natural liquid foods (cow milk, soy milk, and rice milk) were used
      to evaluate the putative ecological impact of these transfers. In cow and soy
      milk, conjugation, mobilization, and retromobilization were shown to occur at
      frequencies of 8.0 x 10(-1), 1.0 x 10(-2), and 1.2 x 10(-4) transconjugants per
      recipient, respectively. These data are comparable to those obtained with LB
      medium and about 10-fold lower than in the case of rice milk. Taken together,
      these results emphasize the potential role of plasmid capture played by B.
      thuringiensis in natural environments.

PMID- 19181806
TI  - Both thiamine uptake and biosynthesis of thiamine precursors are required for
      intracellular replication of Listeria monocytogenes.
AB  - Thiamine pyrophosphate is an essential cofactor involved in central metabolism
      and amino acid biosynthesis and is derived from thiamine (vitamin B(1)). The
      extent to which this metabolite is available to bacterial pathogens replicating
      within host cells is still little understood. Growth studies using modified
      minimal Welshimer's broth (mMWB) supplemented with thiamine or the thiamine
      precursor hydroxymethylpyrimidine (HMP) showed that Listeria monocytogenes, in
      agreement with bioinformatic prediction, is able to synthesize thiamine only in
      the presence of HMP. This appears to be due to a lack of ThiC, which is involved
      in HMP synthesis. The knockout of thiD (lmo0317), which probably catalyzes the
      phosphorylation of HMP, inhibited growth in mMWB supplemented with HMP and
      reduced the replication rate of L. monocytogenes in epithelial cells. Mutation of
      a predicted thiamine transporter gene, lmo1429, led to reduced proliferation of
      L. monocytogenes in mMWB containing thiamine or thiamine phosphates and also
      within epithelial cells but had no influence on the expression of the virulence
      factors Hly and ActA. The toxic thiamine analogue pyrithiamine inhibited growth
      of wild-type strain EGD but not of the transporter mutant EGDDeltathiT. We also
      demonstrated that ThiT binds thiamine, a finding compatible with ThiT acting as
      the substrate-binding component of a multimeric thiamine transporter complex.
      These data provide experimental evidence that Lmo1429 homologs including Bacillus
      YuaJ are necessary for thiamine transport in gram-positive bacteria and are
      therefore proposed to be annotated "ThiT." Taken together, these data indicate
      that concurrent thiamine uptake and biosynthesis of thiamine precursors is a
      strategy of L. monocytogenes and possibly other facultative intracellular
      pathogens to enable proliferation within the cytoplasm.

PMID- 19181807
TI  - An RNA hairpin sequesters the ribosome binding site of the homing endonuclease
      mobE gene.
AB  - Previous transcript mapping of the bacteriophage Aeh1 nrd operon revealed a
      predicted RNA hairpin upstream of the homing endonuclease mobE gene. We
      enzymatically mapped the hairpin, showing that the mobE ribosome binding site is
      sequestered. Cloning of the hairpin upstream of lacZ resulted in reduced beta
      galactosidase activity, consistent with translational regulation.

PMID- 19181808
TI  - Roles of germination-specific lytic enzymes CwlJ and SleB in Bacillus anthracis.
AB  - The structural characteristics of a spore enable it to withstand stresses that
      typically kill a vegetative cell. Spores remain dormant until small molecule
      signals induce them to germinate into vegetative bacilli. Germination requires
      degradation of the thick cortical peptidoglycan by germination-specific lytic
      enzymes (GSLEs). Bacillus anthracis has four putative GSLEs, based upon sequence
      similarities with enzymes in other species: SleB, CwlJ1, CwlJ2, and SleL. In this
      study, the roles of SleB, CwlJ1, and CwlJ2 were examined. The expression levels
      of all three genes peak 3.5 h into sporulation. Genetic analysis revealed that,
      similar to other known GSLEs, none of these gene products are individually
      required for growth, sporulation, or triggering of germination. However, later
      germination events are affected in spores lacking CwlJ1 or SleB. Compared to the
      wild type, germinating spores without CwlJ1 suffer a delay in optical density
      loss and cortex peptidoglycan release. The absence of SleB also causes a delay in
      cortex fragment release. A double mutant lacking both SleB and CwlJ1 is
      completely blocked in cortex hydrolysis and progresses through outgrowth to
      produce colonies at a frequency 1,000-fold lower than that of the wild-type
      strain. A null mutation eliminating CwlJ2 has no effect on germination. High
      performance liquid chromatography and mass spectroscopy analysis revealed that
      SleB is required for lytic transglycosylase activity. CwlJ1 also clearly
      participates in cortex hydrolysis, but its specific mode of action remains
      unclear. Understanding the lytic germination activities that naturally diminish
      spore resistance can lead to methods for prematurely inducing them, thus
      simplifying the process of treating contaminated sites.

PMID- 19181809
TI  - Constant c10 ring stoichiometry in the Escherichia coli ATP synthase analyzed by
      cross-linking.
AB  - The subunit c stoichiometry of Escherichia coli ATP synthase was studied by
      intermolecular cross-linking via oxidation of bi-cysteine-substituted subunit c
      (cA21C/cM65C). Independent of the carbon source used for growth and independent
      of the presence of other FoF1 subunits, an equal pattern of cross-link formation
      stopping at the formation of decamers was obtained.

PMID- 19181810
TI  - Peptide wrwycr inhibits the excision of several prophages and traps holliday
      junctions inside bacteria.
AB  - Peptide inhibitors of phage lambda site-specific recombination were previously
      isolated by screening synthetic combinatorial peptide libraries. These inhibitors
      cause the accumulation of complexes between the recombinase and the Holliday
      junction intermediate of several highly divergent tyrosine recombinases. Peptide
      WRWYCR and its d-amino acid derivative bind to the center of protein-free
      junctions and prevent their resolution either by site-specific recombinases or by
      junction resolvases or helicases. With lesser affinity, the peptides also bind to
      branched DNA molecules that mimic replication forks. The peptides are
      bactericidal to both gram-positive and gram-negative bacteria, presumably because
      they can interfere with DNA repair and with chromosome dimer resolution by the
      XerC and XerD tyrosine recombinases. In order to test the correspondence between
      their mechanism in vivo and in vitro, we have tested and shown peptide wrwycr's
      ability to inhibit the excision of several prophages (lambda, P22, Gifsy-1, Gifsy
      2, Fels-1, Fels-2) and to trap Holliday junction intermediates of phage lambda
      site-specific recombination in vivo. In addition, we found that the peptide
      inhibits replication of the Salmonella prophage Fels-1 while integrated in the
      chromosome. These findings further support the proposed mechanistic basis for the
      antimicrobial activity of the peptide and its use as a tool to dissect strand
      exchange-dependent DNA repair within cells.

PMID- 19181811
TI  - Properties of HflX, an enigmatic protein from Escherichia coli.
AB  - The Escherichia coli gene hflX was first identified as part of the hflA operon,
      mutations in which led to an increased frequency of lysogenization upon infection
      of the bacterium by the temperate coliphage lambda. Independent mutational
      studies have also indicated that the HflX protein has a role in transposition.
      Based on the sequence of its gene, HflX is predicted to be a GTP-binding protein,
      very likely a GTPase. We report here purification and characterization of the
      HflX protein. We also specifically examined its suggested functional roles
      mentioned above. Our results show that HflX is a monomeric protein with a high
      (30% to 40%) content of helices. It exhibits GTPase as well as ATPase activities,
      but it has no role in lambda lysogeny or in transposition.

PMID- 19181812
TI  - Expression and mutational analysis of the glnB genomic region in the heterocyst
      forming Cyanobacterium Anabaena sp. strain PCC 7120.
AB  - In the filamentous, heterocyst-forming cyanobacterium Anabaena sp. strain PCC
      7120, the glnB gene is expressed at considerable levels both in the presence and
      in the absence of combined nitrogen, although induction, influenced by NtcA,
      takes place upon combined-nitrogen deprivation likely localized to vegetative
      cells. In spite of extensive efforts, a derivative of PCC 7120 lacking a
      functional glnB gene could be obtained only with constructs that lead to
      overexpression of a downstream open reading frames (ORF), particularly all2318.
      Strain CSP10 [glnB all2318(Con)] exhibited growth rates similar to those of the
      wild type when it was using nitrate or ammonium, but its diazotrophic growth was
      impaired. However, it differentiated heterocysts with a time course and
      distribution pattern similar to those of the wild type, although with no
      cyanophycin-containing polar granules, and exhibited impaired nitrogenase
      activity under oxic conditions, but not under microoxic conditions. In the
      mutant, NtcA-dependent induction of the hetC and nifH genes was unaltered, but
      induction of the urtA gene and urea transport activity were increased. Active
      uptake of nitrite was also increased and insensitive to the ammonium-promoted
      inhibition observed for the wild type. Thus, regulation of the nitrite transport
      activity requires the glnB gene product. In the presence of a wild-type glnB
      gene, neither inactivation nor overexpression of all2318 produced an apparent
      phenotype. Thus, in an otherwise wild-type background, the glnB gene appears to
      be essential for growth of strain PCC 7120. For growth with combined nitrogen but
      not for diazotrophic growth, the requirement for glnB can be overridden by
      increasing the expression of all2318 (and/or ORFs downstream of it).

PMID- 19181813
TI  - Two redundant sodium-driven stator motor proteins are involved in Aeromonas
      hydrophila polar flagellum rotation.
AB  - Motility is an essential characteristic for mesophilic Aeromonas strains. We
      identified a new polar flagellum region (region 6) in the A. hydrophila AH-3
      (serotype O34) chromosome that contained two additional polar stator genes, named
      pomA2 and pomB2. A. hydrophila PomA2 and PomB2 are highly homologous to other
      sodium-conducting polar flagellum stator motors as well as to the previously
      described A. hydrophila AH-3 PomA and PomB. pomAB and pomA2B2 were present in all
      the mesophilic Aeromonas strains tested and were independent of the strains'
      ability to produce lateral flagella. Unlike MotX, which is a stator protein that
      is essential for polar flagellum rotation, here we demonstrate that PomAB and
      PomA2B2 are redundant sets of proteins, as neither set on its own is essential
      for polar flagellum motility in either aqueous or high-viscosity environments.
      Both PomAB and PomA2B2 are sodium-coupled stator complexes, although PomA2B2 is
      more sensitive to low concentrations of sodium than PomAB. Furthermore, the level
      of transcription in aqueous and high-viscosity environments of pomA2B2 is reduced
      compared to that of pomAB. The A. hydrophila AH-3 polar flagellum is the first
      case described in which two redundant sodium-driven stator motor proteins (PomAB
      and PomA2B2) are found.

PMID- 19181814
TI  - Creation of a large deletion mutant of Campylobacter jejuni reveals that the
      lipooligosaccharide gene cluster is not required for viability.
AB  - Deletion of the lipooligosaccharide biosynthesis region (Cj1132c to Cj1152c) from
      the genome of Campylobacter jejuni NCTC11168 shows that the core is not required
      for viability. The mutant was attenuated for growth and has increased sensitivity
      to antibiotics and detergents. Natural transformation and invasion of cultured
      host cells was abolished.

PMID- 19181815
TI  - The orphan response regulator CovR: a globally negative modulator of virulence in
      Streptococcus suis serotype 2.
AB  - Streptococcus suis serotype 2 is an emerging zoonotic pathogen responsible for a
      wide range of life-threatening diseases in pigs and humans. However, the
      pathogenesis of S. suis serotype 2 infection is not well understood. In this
      study, we report that an orphan response regulator, CovR, globally regulates gene
      expression and negatively controls the virulence of S. suis 05ZYH33, a
      streptococcal toxic shock syndrome (STSS)-causing strain. A covR-defective
      (DeltacovR) mutant of 05ZYH33 displayed dramatic phenotypic changes, such as
      formation of longer chains, production of thicker capsules, and increased
      hemolytic activity. Adherence of the DeltacovR mutant to epithelial cells was
      greatly increased, and its resistance to phagocytosis and killing by neutrophils
      and monocytes was also significantly enhanced. More importantly, inactivation of
      covR increased the lethality of S. suis serotype 2 in experimental infection of
      piglets, and this phenotype was restored by covR complementation. Colonization
      experiments also showed that the DeltacovR mutant exhibited an increased ability
      to colonize susceptible tissues of piglets. The pleiotropic phenotype of the
      DeltacovR mutant is in full agreement with the large number of genes controlled
      by CovR as revealed by transcription profile analysis: 2 genes are positively
      regulated, and 193 are repressed, including many that encode known or putative
      virulence factors. These findings suggested that CovR is a global repressor in
      virulence regulation of STSS-causing S. suis serotype 2.

PMID- 19181816
TI  - Structural and functional importance of transmembrane domain 3 (TM3) in the
      aspartate:alanine antiporter AspT: topology and function of the residues of TM3
      and oligomerization of AspT.
AB  - AspT, the aspartate:alanine antiporter of Tetragenococcus halophilus, a membrane
      protein of 543 amino acids with 10 putative transmembrane (TM) helices, is the
      prototype of the aspartate:alanine exchanger (AAE) family of transporters.
      Because TM3 (isoleucine 64 to methionine 85) has many amino acid residues that
      are conserved among members of the AAE family and because TM3 contains two
      charged residues and four polar residues, it is thought to be located near (or to
      form part of) the substrate translocation pathway that includes the binding site
      for the substrates. To elucidate the role of TM3 in the transport process, we
      carried out cysteine-scanning mutagenesis. The substitutions of tyrosine 75 and
      serine 84 had the strongest inhibitory effects on transport (initial rates of l
      aspartate transport were below 15% of the rate for cysteine-less AspT).
      Considerable but less-marked effects were observed upon the replacement of
      methionine 70, phenylalanine 71, glycine 74, arginine 76, serine 83, and
      methionine 85 (initial rates between 15% and 30% of the rate for cysteine-less
      AspT). Introduced cysteine residues at the cytoplasmic half of TM3 could be
      labeled with Oregon green maleimide (OGM), whereas cysteines close to the
      periplasmic half (residues 64 to 75) were not labeled. These results suggest that
      TM3 has a hydrophobic core on the periplasmic half and that hydrophilic residues
      on the cytoplasmic half of TM3 participate in the formation of an aqueous cavity
      in membranes. Furthermore, the presence of l-aspartate protected the cysteine
      introduced at glycine 62 against a reaction with OGM. In contrast, l-aspartate
      stimulated the reactivity of the cysteine introduced at proline 79 with OGM.
      These results demonstrate that TM3 undergoes l-aspartate-induced conformational
      alterations. In addition, nonreducing sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analyses and a glutaraldehyde cross-linking assay suggest that
      functional AspT forms homo-oligomers as a functional unit.

PMID- 19181817
TI  - Generation of branched-chain fatty acids through lipoate-dependent metabolism
      facilitates intracellular growth of Listeria monocytogenes.
AB  - The gram-positive bacterial pathogen Listeria monocytogenes has evolved
      mechanisms to rapidly replicate in the host cytosol, implying efficient
      utilization of host-derived nutrients. However, the contribution of host nutrient
      scavenging versus that of bacterial biosynthesis toward rapid intracellular
      growth remains unclear. Nutrients that contribute to growth of L. monocytogenes
      include branched-chain fatty acids (BCFAs), amino acids, and other metabolic
      intermediates generated from acyl-coenzyme A, which is synthesized using
      lipoylated metabolic enzyme complexes. To characterize which biosynthetic
      pathways support replication of L. monocytogenes inside the host cytosol, we
      impaired lipoate-dependent metabolism by disrupting two lipoate ligase genes that
      are responsible for bacterial protein lipoylation. Interrupting lipoate-dependent
      metabolism modestly impaired replication in rich broth medium but strongly
      inhibited growth in defined medium and host cells and impaired the generation of
      BCFAs. Addition of short BCFAs and amino acids restored growth of the A1A2
      deficient (A1A2-) mutant in minimal medium, implying that lipoate-dependent
      metabolism generates amino acids and BCFAs. BCFAs alone rescued intracellular
      growth and spread in L2 fibroblasts of the A1A2- mutant. Lipoate-dependent
      metabolism was also required in vivo, as a wild-type strain robustly outcompeted
      the lipoylation-deficient mutant in a murine model of listeriosis. The results of
      this study suggest that lipoate-dependent metabolism contributes to both amino
      acid and BCFA biosynthesis and that BCFA biosynthesis is preferentially required
      for intracellular growth of L. monocytogenes.

PMID- 19181818
TI  - Role of Clp proteins in expression of virulence properties of Streptococcus
      mutans.
AB  - Mutational analysis revealed that members of the Clp system, specifically the
      ClpL chaperone and the ClpXP proteolytic complex, modulate the expression of
      important virulence attributes of Streptococcus mutans. Compared to its parent,
      the DeltaclpL strain displayed an enhanced capacity to form biofilms in the
      presence of sucrose, had reduced viability, and was more sensitive to acid
      killing. The DeltaclpP and DeltaclpX strains displayed several phenotypes in
      common: slow growth, tendency to aggregate in culture, reduced autolysis, and
      reduced ability to grow under stress, including acidic pH. Unexpectedly, the
      DeltaclpP and DeltaclpX mutants were more resistant to acid killing and
      demonstrated enhanced viability in long-term survival assays. Biofilm formation
      by the DeltaclpP and DeltaclpX strains was impaired when grown in glucose but
      enhanced in sucrose. In an animal study, the average number of S. mutans colonies
      recovered from the teeth of rats infected with the DeltaclpP or DeltaclpX strain
      was slightly lower than that of the parent strain. In Bacillus subtilis, the
      accumulation of the Spx global regulator, a substrate of ClpXP, has accounted for
      the DeltaclpXP phenotypes. Searching the S. mutans genome, we identified two
      putative spx genes, designated spxA and spxB. The inactivation of either of these
      genes bypassed phenotypes of the clpP and clpX mutants. Western blotting
      demonstrated that Spx accumulates in the DeltaclpP and DeltaclpX strains. Our
      results reveal that the proteolysis of ClpL and ClpXP plays a role in the
      expression of key virulence traits of S. mutans and indicates that the underlying
      mechanisms by which ClpXP affect virulence traits are associated with the
      accumulation of two Spx orthologues.

PMID- 19181819
TI  - School functioning in adolescents with chronic pain: the role of depressive
      symptoms in school impairment.
AB  - OBJECTIVE: To explore associations between depressive symptoms and school
      functioning, including school attendance, academic performance, self-perceived
      academic competence, and teacher-rated school adjustment among predominantly
      Caucasian and female adolescent chronic pain patients. METHODS: A total of 217
      clinically referred adolescents (aged 12-17 years) and their parents completed
      measures of pain characteristics, depression, and school functioning. Additional
      data were collected from school records and teacher reports. RESULTS: Depressive
      symptoms strongly correlated with school functioning indicators. In linear
      regression analyses, higher levels of depressive symptoms predicted more school
      impairment. A model testing whether depressive symptoms mediated the association
      between current pain intensity and parent perceptions of the interference of pain
      on school functioning was supported by the data. CONCLUSIONS: Depressive symptoms
      play a key role in influencing the extent of school impairment in adolescents
      with chronic pain. Interventions to alleviate depressive symptoms may enhance
      treatments designed to improve school functioning in this population.

PMID- 19181822
TI  - Would physician-assisted suicide jeopardize trust in the medical services? An
      empirical study of attitudes among the general public in Sweden.
AB  - AIM: To investigate the attitudes among the Swedish population towards physician
      assisted suicide, with special regard to the possible effects on trust in the
      medical services of physician-assisted suicide being allowed. DESIGN: A postal
      questionnaire about physician-assisted suicide under certain conditions and its
      possible influence on trust in the medical services was distributed to 1206
      randomly selected individuals living in the county of Stockholm. Two reminders
      were distributed, followed by a short version of the questionnaire containing
      only the question about the attitude towards physician-assisted suicide. RESULTS:
      The total response rate was 51%, a short-version reminder adding another 7%. Of
      all participants, 73% were in favour of physician-assisted suicide, 12% were
      against, and 15% were undecided. They believed that their trust in the medical
      services would increase (38%) or not be influenced at all (45%) if physician
      assisted suicide were to be allowed. However, 75% of those who were against
      physician-assisted suicide believed that their trust would decrease. As compared
      to those reporting high trust in medical services (n = 492), those with low trust
      (n = 97) stated that their trust would increase, 36% (confidence interval (CI) =
      35-37%) vs. 49% (95% CI = 39-59%). Thirty-three per cent (95% CI = 28-38%) of the
      younger respondents (<50 years), and 43% (95% CI = 37-49%) of the older
      respondents believed that their trust would increase. CONCLUSIONS: We found no
      evidence for the assumption that trust in the medical services would be
      unambiguously jeopardized if physician-assisted suicide were to be legalized.
      Only among the minority who opposed physician-assisted suicide did a majority of
      respondents report that their trust would decrease.

PMID- 19181820
TI  - Cultural factors and family-based HIV prevention intervention for Latino youth.
AB  - Latino youth are the fastest growing ethnic group in the United States and are at
      considerable risk for HIV and other sexually transmitted infections (STIs), given
      that they have an earlier onset of sexual activity and use condoms less
      consistently than European American adolescents. Theorists and scholars have
      emphasized the importance of taking culture into account in sexuality
      interventions with Latino adolescents, yet few culturally tailored interventions
      have been developed for this population. Given the emphasis on familismo and
      collectivism among Latinos, family-based programs are likely to be well received
      and could contribute to long-term maintenance of adolescent safety. In this
      synthesis of the relevant literature, cultural factors that have been identified
      as relevant to Latino sexuality are reviewed and implications for family-based
      intervention with Latinos are addressed.

PMID- 19181821
TI  - A randomized lifestyle intervention with 5-year follow-up in subjects with
      impaired glucose tolerance: pronounced short-term impact but long-term adherence
      problems.
AB  - AIMS: To compare data on cardiovascular risk factor changes in lipids, insulin,
      proinsulin, fibrinolysis, leptin and C-reactive protein, and on diabetes
      incidence, in relation to changes in lifestyle. METHODS: The study was a
      randomized lifestyle intervention trial conducted in northern Sweden between 1995
      and 2000, in 168 individuals with impaired glucose tolerance (IGT) and body mass
      index above 27 at start. The intensive intervention group (n = 83) was subjected
      to a 1-month residential lifestyle programme. The usual care group (n = 85)
      participated in a health examination ending with a single counselling session.
      Follow-up was conducted at 1, 3 and 5 years. RESULTS: At 1-year follow-up, an
      extensive cardio-metabolic risk factor reduction was demonstrated in the
      intensive intervention group, along with a 70% decrease of progress to type 2
      diabetes. At 5-year follow-up, most of these beneficial effects had disappeared.
      Reported physical activity and fibre intake as well as high-density lipoprotein
      cholesterol were still increased, and fasting insulin and proinsulin were lower.
      CONCLUSIONS: The intervention affected several important cardio-metabolic risk
      variables beneficially, and reduced the risk for type 2 diabetes, but the effects
      persisted only as long as the new lifestyle was maintained. Increased physical
      activity seemed to be the behaviour that was most easy to preserve.

PMID- 19181823
TI  - Disability pension is associated with the use of benzodiazepines 20 years later:
      a prospective study.
AB  - AIM: The Norwegian government states that actions are needed to stimulate working
      capacity in disability pension (DP) recipients with such a potential.
      Identification of factors that may impair rehabilitation efforts, such as
      information on the start of benzodiazepines in DP recipients, may be useful in
      this context.Thus, the aim of the study was to describe the association between
      receipt of DP and later prescriptions of benzodiazepines among non-users at
      baseline. METHODS: We followed a cohort reporting non-use of benzodiazepines,
      6645 men and 6455 women aged 40-42 years who underwent health surveys in 1985-89
      in two Norwegian counties, with respect to subsequent use of benzodiazepines by
      linkage to the Norwegian Prescription Database for 2004-2006. At baseline, 83 men
      and 163 women reported receiving DP. RESULTS: In both genders, the proportion
      started on at least one prescription of a benzodiazepine was approximately
      doubled among those reporting being on a DP 20 years in the past, 21% of all men
      and 29% of all women, respectively. Univariate odds ratios for a benzodiazepine
      prescription for men and women on a DP were 2.6 (95% confidence interval (CI) =
      1.5-4.4) and 2.1 (95% CI = 1.5-2.9), respectively, as compared with those not
      receiving a DP. After adjustment for alcohol use, smoking habits, physical
      activity, socioeconomic and health variables, the odds ratios were lowered for
      both genders, being 2.1 (95% CI = 1.2-3.7) (men) and 1.6 (95% CI = 1.1-2.3)
      (women). CONCLUSIONS: For both men and women, the chance of being prescribed
      benzodiazepines was higher among those reporting being DP recipients 20 years in
      the past.

PMID- 19181824
TI  - Risk factors for cardiovascular diseases and diabetes in disability pensioners
      aged 40--42 years: a cross-sectional study in Norway.
AB  - AIMS: Few disability pensions at the age of 40 in Norway are granted due to
      cardiovascular diseases (CVD) or diabetes, but disability pensioners have an
      excess mortality of these diseases. In this study, we aim to present risk factors
      for CVD and diabetes in young disability pensioners, compared with persons able
      to work. METHODS: A population-based survey of Norwegian men and women aged 40-42
      years was conducted in 1997-1999, with 62,778 participants. Disability pensioners
      (n= 2636) and other non-working persons (n = 5105) were compared with persons
      able to work. Risk factors were compared in persons without CVD and diabetes.
      RESULTS: Prevalence of self-reported CVD and diabetes was markedly higher in
      disability pensioners than in persons able to work. In persons without these
      diseases, we found elevations of all measured risk factors were more prevalent in
      disabled men and women. Myocardial infarction risk was about 50% higher in
      disability pensioners. Disability pensioners were more physically inactive and
      obese; they smoked more and had lipid disorders with elevated total cholesterol,
      low high-density lipoprotein (hdl)-cholesterol and elevated triglycerides. Other
      non-working persons had less pronounced elevations of most of the risk factors.
      CONCLUSIONS: A high proportion of disability pensioners and others not working at
      the age of 40 had an elevated risk for CVD and diabetes.

PMID- 19181825
TI  - Health care of children living with their mother in prison compared with the
      general population.
AB  - BACKGROUND: Italian law allows female prisoners in specific "nest areas" to keep
      their babies with them until the child reaches the age of 3 years. We describe
      health care of children living in the nest areas and we compare this condition
      with the general population. METHODS: Our study was conducted in the female
      detention centre of Rome Rebibbia, Italy. Clinical diaries of all babies have
      been screened. The pediatrics ambulatory of A. Gemelli Hospital of Rome provided
      all data for comparison. RESULTS: We describe 391 children (150 in the prison
      group, G1; 150 children with Italian parents, G2, and 91 children with foreign
      parents, G3) with similar characteristics. There were statistical differences
      between-groups in respect of the auxological data, gestational age (lower in G1
      vs G2, p < 0.0004, and lower in G1 vs G3, p < 0.03), time of weaning age earlier
      in G1 vs G2, (p < 0.035), number of respiratory infective disease (G1>G2, p <
      0.0001, and G1>G3, p < 0.003). We also found inadequate immunisation status in
      children at their admission to prison. According to our observations children
      received good sanitary assistance inside the prison and the adjustment of their
      immunisation status when they stayed in prison for a long enough period.
      CONCLUSIONS: The significant information shown by our data suggest that children
      living in prison with their mothers represent a vulnerable group with particular
      healthcare needs.

PMID- 19181826
TI  - A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug
      combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and
      cisplatin (TP) followed by radical surgery in patients with locally advanced
      squamous cell cervical carcinoma: the Snap-02 Italian Collaborative Study.
AB  - BACKGROUND: The efficacy and tolerability of the regimen containing paclitaxel
      and cisplatin (TP) in the neo-adjuvant treatment of locally advanced squamous
      cell cervical cancer are unknown. The TIP regimen (TP plus ifosfamide) showed
      high efficacy but high toxicity and it is used as an internal control. PATIENTS
      AND METHODS: In all, 154 patients were randomized to TP (paclitaxel 175 mg/m(2) +
      cisplatin 75 mg/m(2); n = 80) or TIP (TP + ifosfamide 5 g/m(2); n = 74), three
      cycles, followed by radical surgery. Pathological response to chemotherapy was
      classified as optimal [no residual tumor (complete response) or residual disease
      with < or = 3 mm stromal invasion (PR1)] or suboptimal response. RESULTS: Patient
      characteristics (TP/TIP): stage IB2 (56%/64%), IIA (18%/14%), IIB (20%/19%), III
      IVA (5%/4%) and median age (42 years/45 years). The optimal response rate in the
      TP group was 25%, 95% confidence interval (CI) = 16% to 37% and 43%, 95% CI = 31%
      to 55% in the TIP group. Grades 3-4 leukopenia (6%/53%) and neutropenia (26%/76%)
      were significantly more frequent on TIP. CONCLUSION: TP performance was below
      expectation since the lower 95% confidence limit of the optimal response rate
      failed to reach the prespecified minimum requirement of efficacy, i.e. 22%. The
      TIP regimen confirmed its activity but was associated with higher haematological
      toxicity than TP.

PMID- 19181828
TI  - Interactions between coexisting intracellular genomes: mitochondrial density and
      Wolbachia infection.
AB  - Many arthropods are infected with maternally transmitted microorganisms, leading
      to the coexistence of several intracellular genomes within the host cells,
      including their own mitochondria. As these genomes are cotransmitted, their
      patterns of evolution have been intimately linked, with possible consequences for
      the diversity and evolution of the host mitochondrial DNA. The evolutionary
      aspects of the situation have been thoroughly investigated, especially the
      selective sweep on the mitochondria as a result of Wolbachia invasion, whereas
      direct interactions between mitochondria and intracellular symbionts within the
      host cells or body have received little attention. Since endosymbionts exploit
      host resources but mitochondria supply energy to meet the bioenergetic demands of
      organisms, an unanswered question concerns the correlation between their
      densities. Here, we investigated the influence of Wolbachia symbiosis on
      mitochondrial density in two parasitic wasps of Drosophila species, both of which
      are naturally infected by three Wolbachia strains, but they differ in their
      degree of dependency on these bacteria. In Leptopilina heterotoma, all Wolbachia
      strains are facultative, whereas Asobara tabida requires a strain of Wolbachia
      for oogenesis to occur. In both species, Wolbachia infections are stable and well
      regulated, since the density of each strain does not depend on the presence or
      absence of other strains. Using lines that harbor various Wolbachia infection
      statuses, we found that mitochondrial density was not affected by the infection
      regardless of the sex and age of the host, which is strongly reminiscent of the
      independent regulation of specific Wolbachia strains and suggest that the
      protagonists coexist independently of each other as the result of a long-term
      coevolutionary interaction.

PMID- 19181827
TI  - Selection of Sphingomonadaceae at the base of Laccaria proxima and Russula
      exalbicans fruiting bodies.
AB  - The dense hyphal network directly underneath the fruiting bodies of
      ectomycorrhizal fungi might exert strong influences on the bacterial community of
      soil. Such fruiting bodies might serve as hot spots for bacterial activity, for
      instance by providing nutrients and colonization sites in soil. Here, we assessed
      the putative selection of specific members of the Sphingomonadaceae family at the
      bases of the fruiting bodies of the ectomycorrhizal fungi Laccaria proxima and
      Russula exalbicans in comparison to the adjacent bulk soil. To do so, we used a
      previously designed Sphingomonadaceae-specific PCR-denaturing gradient gel
      electrophoresis (DGGE) system and complemented this with analyses of sequences
      from a Sphingomonadaceae-specific clone library. The analyses showed clear
      selective effects of the fruiting bodies of both fungi on the Sphingomonadaceae
      community structures. The effect was especially prevalent with R. exalbicans.
      Strikingly, similar fungi sampled approximately 100 m apart showed similar DGGE
      patterns, while corresponding bulk soil-derived patterns differed from each
      other. However, the mycospheres of L. proxima and R. exalbicans still revealed
      divergent community structures, indicating that different fungi select for
      different members of the Sphingomonadaceae family. Excision of specific bands
      from the DGGE patterns, as well as analyses of the clone libraries generated from
      both habitats, revealed fruiting body-specific Sphingomonadaceae types. It
      further showed that major groups from the mycospheres of R. exalbicans and L.
      proxima did not cluster with known bacteria from the database, indicating new
      groups within the family of Sphingomonadaceae present in these environments.

PMID- 19181829
TI  - Codon-optimized fluorescent proteins designed for expression in low-GC gram
      positive bacteria.
AB  - Fluorescent proteins have wide applications in biology. However, not all of these
      proteins are properly expressed in bacteria, especially if the codon usage and
      genomic GC content of the host organism are not ideal for high expression. In
      this study, we analyzed the DNA sequences of multiple fluorescent protein genes
      with respect to codons and GC content and compared them to a low-GC gram-positive
      bacterium, Bacillus anthracis. We found high discrepancies for cyan fluorescent
      protein (CFP), yellow fluorescent protein (YFP), and the photoactivatable green
      fluorescent protein (PAGFP), but not GFP, with regard to GC content and codon
      usage. Concomitantly, when the proteins were expressed in B. anthracis, CFP- and
      YFP-derived fluorescence was undetectable microscopically, a phenomenon caused
      not by lack of gene transcription or degradation of the proteins but by lack of
      protein expression. To improve expression in bacteria with low genomic GC
      contents, we synthesized a codon-optimized gfp and constructed optimized
      photoactivatable pagfp, cfp, and yfp, which were in contrast to nonoptimized
      genes highly expressed in B. anthracis and in another low-GC gram-positive
      bacterium, Staphylococcus aureus. Using optimized GFP as a reporter, we were able
      to monitor the activity of the protective antigen promoter of B. anthracis and
      confirm its dependence on bicarbonate and regulators present on virulence plasmid
      pXO1.

PMID- 19181830
TI  - Diverse and novel nifH and nifH-like gene sequences in the deep-sea methane seep
      sediments of the Okhotsk Sea.
AB  - Diverse nifH and nifH-like gene sequences were obtained from the deep-sea surface
      sediments of the methane hydrate-bearing Okhotsk Sea. Some sequences formed novel
      families of the NifH or NifH-like proteins, of currently unresolved bacterial or
      archaeal origin. Comparison with other marine environments indicates
      environmental specificity of some of the sequences, either unique to the methane
      seep sediments of the Okhotsk Sea or to the general deep-sea methane seep
      sedimentary environments.

PMID- 19181831
TI  - Stress- and growth rate-related differences between plate count and real-time PCR
      data during growth of Listeria monocytogenes.
AB  - To assess the overestimation of bacterial cell counts in real-time PCR in
      relation to stress and growth phase, four different strains of L. monocytogenes
      were exposed to combinations of osmotic stress (0.5 to 8% [vol/vol] NaCl) and
      acid stress (pH 5 to 7) in a culture model at a growth temperature of 10 degrees
      C or were grown under optimal conditions. Growth curves obtained from real-time
      PCR, optical density, and viable count data were compared. As expected, optical
      density data revealed entirely different growth curves. Good to moderate growth
      conditions yielded good correlation of real-time PCR data and plate count data
      (r(2) = 0.96 and 0.99) with similar cell counts. When growth conditions became
      worse, the numbers of CFU decreased during the stationary phase, whereas real
      time-PCR-derived bacterial cell equivalents differed in this regard; the
      correlation worsened (r(2) = 0.84). However, fitted growth curves revealed that
      maximum growth rates calculated from real-time PCR data were not significantly
      different from those derived from plate count data. The overestimation of
      bacterial cell counts by real-time PCR observed in the stationary phase under
      higher-stress conditions might be explained by the accumulation of viable but
      nonculturable bacteria or dead bacteria and extracellular DNA. Considering these
      results, real-time PCR data collected from naturally contaminated samples should
      be viewed with caution.

PMID- 19181832
TI  - Complete genome of the broad-host-range Erwinia amylovora phage phiEa21-4 and its
      relationship to Salmonella phage felix O1.
AB  - The first complete genome sequence for a myoviridal bacteriophage, PhiEa21-4,
      infecting Erwinia amylovora, Erwinia pyrifoliae, and Pantoea agglomerans strains
      has been determined. The unique sequence of this terminally redundant, circularly
      permuted genome is 84,576 bp. The PhiEa21-4 genome has a GC content of 43.8% and
      contains 117 putative protein-coding genes and 26 tRNA genes. PhiEa21-4 is the
      first phage in which a precisely conserved rho-independent terminator has been
      found dispersed throughout the genome, with 24 copies in all. Also notable in the
      PhiEa21-4 genome are the presence of tRNAs with six- and nine-base anticodon
      loops, the absence of a small packaging terminase subunit, and the presence of
      nadV, a principle component of the NAD(+) salvage pathway, which has been found
      in only a few phage genomes to date. PhiEa21-4 is the first reported Felix O1
      like phage genome; 56% of the predicted PhiEa21-4 proteins share homology with
      those of the Salmonella phage. Apart from this similarity to Felix O1, the
      PhiEa21-4 genome appears to be substantially different, both globally and
      locally, from previously reported sequences. A total of 43 of the 117 genes are
      unique to PhiEa21-4, and 32 of the Felix O1-like genes do not appear in any phage
      genome sequences other than PhiEa21-4 and Felix O1. N-terminal sequencing and
      matrix-assisted laser desorption ionization-time of flight analysis resulted in
      the identification of five PhiEa21-4 genes coding for virion structural proteins,
      including the major capsid protein.

PMID- 19181833
TI  - Construction of disarmed Ti plasmids transferable between Escherichia coli and
      Agrobacterium species.
AB  - Agrobacterium-mediated plant transformation has been used widely, but there are
      plants that are recalcitrant to this type of transformation. This transformation
      method uses bacterial strains harboring a modified tumor-inducing (Ti) plasmid
      that lacks the transfer DNA (T-DNA) region (disarmed Ti plasmid). It is desirable
      to develop strains that can broaden the host range. A large number of
      Agrobacterium strains have not been tested yet to determine whether they can be
      used in transformation. In order to improve the disarming method and to obtain
      strains disarmed and ready for the plant transformation test, we developed a
      simple scheme to make certain Ti plasmids disarmed and simultaneously
      maintainable in Escherichia coli and mobilizable between E. coli and
      Agrobacterium. To establish the scheme in nopaline-type Ti plasmids, a
      neighboring segment to the left of the left border sequence, a neighboring
      segment to the right of the right border sequence of pTi-SAKURA, a cassette
      harboring the pSC101 replication gene between these two segments, the broad-host
      range IncP-type oriT, and the gentamicin resistance gene were inserted into a
      suicide-type sacB-containing vector. Replacement of T-DNA with the cassette in
      pTiC58 and pTi-SAKURA occurred at a high frequency and with high accuracy when
      the tool plasmid was used. We confirmed that there was stable maintenance of the
      modified Ti plasmids in E. coli strain S17-1lambdapir and conjugal transfer from
      E. coli to Ti-less Agrobacterium strains and that the reconstituted Agrobacterium
      strains were competent to transfer DNA into plant cells. As the modified plasmid
      delivery system was simple and efficient, conversion of strains to the disarmed
      type was easy and should be applicable in studies to screen for useful strains.

PMID- 19181834
TI  - Interaction of Bacillus thuringiensis Cry1 and Vip3A proteins with Spodoptera
      frugiperda midgut binding sites.
AB  - Vip3Aa, Vip3Af, Cry1Ab, and Cry1Fa were tested for their toxicities and binding
      interactions. Vip3A proteins were more toxic than Cry1 proteins. Binding assays
      showed independent specific binding sites for Cry1 and Vip3A proteins. Cry1Ab and
      Cry1Fa competed for the same binding sites, whereas Vip3Aa competed for those of
      Vip3Af.

PMID- 19181835
TI  - Insights into structure-activity relationships in the C-terminal region of
      divercin V41, a class IIa bacteriocin with high-level antilisterial activity.
AB  - Divercin V41 (DvnV41) is a class IIa bacteriocin with potent antilisterial
      activity isolated from Carnobacterium divergens V41. Previously, we expressed
      from a synthetic gene, in Escherichia coli Origami, a recombinant DvnV41
      designated DvnRV41, which possesses four additional amino acids (AMDP) in the N
      terminal region that result from enzymatic cleavage and retains the initial
      DvnV41 activity. To unravel the relationship between the structure of DvnRV41 and
      its particularly elevated activity, we produced by site-directed mutagenesis
      eight variants in which a single amino acid replacement was specifically
      introduced into the sequence. The point mutations were designed to change either
      conserved residues in class IIa bacteriocins or residues specific to DvnV41
      located mainly in the C-terminal region. The fusion proteins were purified from
      the cytosoluble fractions by immobilized affinity chromatography. DvnRV41 and its
      variants were released from the fusion proteins by enzymatic cleavage, using
      enterokinase. The purity of DvnRV41 and of the variants was checked by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, high-performance liquid
      chromatography, and mass spectrometry. The antibacterial activity of DvnRV41 and
      its variants was assessed using different indicator strains, including Listeria
      monocytogenes EGDe and Enterococcus faecalis JH2-2. The activity of all of the
      variants appeared to be less than the activity of DvnRV41. The decrease in
      activity did not appear to be related to a global conformational change, as
      determined by circular dichroism. Overall, the variants of DvnRV41 produced in
      the present study provide interesting insights into structure-activity
      relationships of class IIa bacteriocins.

PMID- 19181836
TI  - Dynamics of polyphosphate-accumulating bacteria in wastewater treatment plant
      microbial communities detected via DAPI (4',6'-diamidino-2-phenylindole) and
      tetracycline labeling.
AB  - Wastewater treatment plants with enhanced biological phosphorus removal represent
      a state-of-the-art technology. Nevertheless, the process of phosphate removal is
      prone to occasional failure. One reason is the lack of knowledge about the
      structure and function of the bacterial communities involved. Most of the
      bacteria are still not cultivable, and their functions during the wastewater
      treatment process are therefore unknown or subject of speculation. Here, flow
      cytometry was used to identify bacteria capable of polyphosphate accumulation
      within highly diverse communities. A novel fluorescent staining technique for the
      quantitative detection of polyphosphate granules on the cellular level was
      developed. It uses the bright green fluorescence of the antibiotic tetracycline
      when it complexes the divalent cations acting as a countercharge in polyphosphate
      granules. The dynamics of cellular DNA contents and cell sizes as growth
      indicators were determined in parallel to detect the most active polyphosphate
      accumulating individuals/subcommunities and to determine their phylogenetic
      affiliation upon cell sorting. Phylotypes known as polyphosphate-accumulating
      organisms, such as a "Candidatus Accumulibacter"-like phylotype, were found, as
      well as members of the genera Pseudomonas and Tetrasphaera. The new method allows
      fast and convenient monitoring of the growth and polyphosphate accumulation
      dynamics of not-yet-cultivated bacteria in wastewater bacterial communities.

PMID- 19181837
TI  - Indole-diterpene biosynthetic capability of epichloe endophytes as predicted by
      ltm gene analysis.
AB  - Bioprotective alkaloids produced by Epichloe and closely related asexual
      Neotyphodium fungal endophytes protect their grass hosts from insect and
      mammalian herbivory. One class of these compounds, known for antimammalian
      toxicity, is the indole-diterpenes. The LTM locus of Neotyphodium lolii (Lp19)
      and Epichloe festuce (Fl1), required for the biosynthesis of the indole-diterpene
      lolitrem, consists of 10 ltm genes. We have used PCR and Southern analysis to
      screen a broad taxonomic range of 44 endophyte isolates to determine why indole
      diterpenes are present in so few endophyte-grass associations in comparison to
      that of the other bioprotective alkaloids, which are more widespread among the
      endophtyes. All 10 ltm genes were present in only three epichloe endophytes. A
      predominance of the asexual Neotyphodium spp. examined contained 8 of the 10 ltm
      genes, with only one N. lolii containing the entire LTM locus and the ability to
      produce lolitrems. Liquid chromatography-tandem mass spectrometry profiles of
      indole-diterpenes from a subset of endophyte-infected perennial ryegrass showed
      that endophytes that contained functional genes present in ltm clusters 1 and 2
      were capable of producing simple indole-diterpenes such as paspaline, 13
      desoxypaxilline, and terpendoles, compounds predicted to be precursors of
      lolitrem B. Analysis of toxin biosynthesis genes by PCR now enables a diagnostic
      method to screen endophytes for both beneficial and detrimental alkaloids and can
      be used as a resource for screening isolates required for forage improvement.

PMID- 19181838
TI  - Improved fermentation performance of a lager yeast after repair of its AGT1
      maltose and maltotriose transporter genes.
AB  - The use of more concentrated, so-called high-gravity and very-high-gravity (VHG)
      brewer's worts for the manufacture of beer has economic and environmental
      advantages. However, many current strains of brewer's yeasts ferment VHG worts
      slowly and incompletely, leaving undesirably large amounts of maltose and
      especially maltotriose in the final beers. alpha-Glucosides are transported into
      Saccharomyces yeasts by several transporters, including Agt1, which is a good
      carrier of both maltose and maltotriose. The AGT1 genes of brewer's ale yeast
      strains encode functional transporters, but the AGT1 genes of the lager strains
      studied contain a premature stop codon and do not encode functional transporters.
      In the present work, one or more copies of the AGT1 gene of a lager strain were
      repaired with DNA sequence from an ale strain and put under the control of a
      constitutive promoter. Compared to the untransformed strain, the transformants
      with repaired AGT1 had higher maltose transport activity, especially after growth
      on glucose (which represses endogenous alpha-glucoside transporter genes) and
      higher ratios of maltotriose transport activity to maltose transport activity.
      They fermented VHG (24 degrees Plato) wort faster and more completely, producing
      beers containing more ethanol and less residual maltose and maltotriose. The
      growth and sedimentation behaviors of the transformants were similar to those of
      the untransformed strain, as were the profiles of yeast-derived volatile aroma
      compounds in the beers.

PMID- 19181839
TI  - Evolutionary history of the phl gene cluster in the plant-associated bacterium
      Pseudomonas fluorescens.
AB  - Pseudomonas fluorescens is of agricultural and economic importance as a
      biological control agent largely because of its plant association and production
      of secondary metabolites, in particular 2,4-diacetylphloroglucinol (2,4-DAPG).
      This polyketide, which is encoded by the eight-gene phl cluster, has
      antimicrobial effects on phytopathogens, promotes amino acid exudation from plant
      roots, and induces systemic resistance in plants. Despite its importance, 2,4
      DAPG production is limited to a subset of P. fluorescens strains. Determination
      of the evolution of the phl cluster and understanding the selective pressures
      promoting its retention or loss in lineages of P. fluorescens will help in the
      development of P. fluorescens as a viable and effective inoculant for application
      in agriculture. In this study, genomic and sequence-based approaches were
      integrated to reconstruct the phylogeny of P. fluorescens and the phl cluster. It
      was determined that 2,4-DAPG production is an ancestral trait in the species P.
      fluorescens but that most lineages have lost this capacity through evolution.
      Furthermore, intragenomic recombination has relocated the phl cluster within the
      P. fluorescens genome at least three times, but the integrity of the cluster has
      always been maintained. The possible evolutionary and functional implications for
      retention of the phl cluster and 2,4-DAPG production in some lineages of P.
      fluorescens are discussed.

PMID- 19181840
TI  - Inc A/C plasmids are prevalent in multidrug-resistant Salmonella enterica
      isolates.
AB  - Bacterial plasmids are fragments of extrachromosomal double-stranded DNA that can
      contain a variety of genes that are beneficial to the host organism, like those
      responsible for antimicrobial resistance. The objective of this study was to
      characterize a collection of 437 Salmonella enterica isolates from different
      animal sources for their antimicrobial resistance phenotypes and plasmid replicon
      types and, in some cases, by pulsed-field gel electrophoresis (PFGE) in an effort
      to learn more about the distribution of multidrug resistance in relation to
      replicon types. A PCR-based replicon typing assay consisting of three multiplex
      PCRs was used to detect 18 of the 26 known plasmid types in the
      Enterobacteriaceae based on their incompatibility (Inc) replicon types. Linkage
      analysis was completed with antibiograms, replicon types, serovars, and Inc A/C.
      Inc A/C plasmids were prevalent in multidrug-resistant isolates with the notable
      exception of Salmonella enterica serovar Typhimurium. Cluster analysis based on
      PFGE of a subset of 216 isolates showed 155 unique types, suggesting a variable
      population, but distinct clusters of isolates with Inc A/C plasmids were
      apparent. Significant linkage of serovar was also seen with Inc replicon types
      B/O, I1, Frep, and HI1. The present study showed that the combination of
      Salmonella, the Inc A/C plasmids, and multiple-drug-resistant genes is very old.
      Our results suggest that some strains, notably serovar Typhimurium and closely
      related types, may have once carried the plasmid but that the resistance genes
      were transferred to the chromosome with the subsequent loss of the plasmid.

PMID- 19181841
TI  - Massively parallel sequencing of the polyadenylated transcriptome of C. elegans.
AB  - Using massively parallel sequencing by synthesis methods, we have surveyed the
      polyA+ transcripts from four stages of the nematode Caenorhabditis elegans to an
      unprecedented depth. Using novel statistical approaches, we evaluated the
      coverage of annotated features of the genome and of candidate processed
      transcripts, including splice junctions, trans-spliced leader sequences, and
      polyadenylation tracts. The data provide experimental support for >85% of the
      annotated protein-coding transcripts in WormBase (WS170) and confirm additional
      details of processing. For example, the total number of confirmed splice
      junctions was raised from 70,911 to over 98,000. The data also suggest thousands
      of modifications to WormBase annotations and identify new spliced junctions and
      genes not part of any WormBase annotation, including at least 80 putative genes
      not found in any of three predicted gene sets. The quantitative nature of the
      data also suggests that mRNA levels may be measured by this approach with
      unparalleled precision. Although most sequences align with protein-coding genes,
      a small fraction falls in introns and intergenic regions. One notable region on
      the X chromosome encodes a noncoding transcript of >10 kb localized to somatic
      nuclei.

PMID- 19181842
TI  - Odor coding by modules of coherent mitral/tufted cells in the vertebrate
      olfactory bulb.
AB  - Odor representation in the olfactory bulb (OB) undergoes a transformation from a
      combinatorial glomerular map to a distributed mitral/tufted (M/T) cell code. To
      understand this transformation, we analyzed the odor representation in large
      populations of individual M/T cells in the Xenopus OB. The spontaneous [Ca(2+)]
      activities of M/T cells appeared to be irregular, but there were groups of
      spatially distributed neurons showing synchronized [Ca(2+)] activities. These
      neurons were always connected to the same glomerulus. Odorants elicited complex
      spatiotemporal response patterns in M/T cells where nearby neurons generally
      showed little correlation. But the responses of neurons connected to the same
      glomerulus were virtually identical, irrespective of whether the responses were
      excitatory or inhibitory, and independent of the distance between them.
      Synchronous neurons received correlated EPSCs and were coupled by electrical
      conductances that could account for the correlated responses. Thus, at the output
      stage of the OB, odors are represented by modules of distributed and synchronous
      M/T cells associated with the same glomeruli. This allows for parallel input to
      higher brain centers.

PMID- 19181844
TI  - Cytokine-induced memory-like natural killer cells.
AB  - The mammalian immune response to infection is mediated by 2 broad arms, the
      innate and adaptive immune systems. Innate immune cells are a first-line defense
      against pathogens and are thought to respond consistently to infection,
      regardless of previous exposure, i.e., they do not exhibit memory of prior
      activation. By contrast, adaptive immune cells display immunologic memory that
      has 2 basic characteristics, antigen specificity and an amplified response upon
      subsequent exposure. Whereas adaptive immune cells have rearranged receptor genes
      to recognize the universe of antigens, natural killer (NK) cells are innate
      immune lymphocytes with a limited repertoire of germ-line encoded receptors for
      target recognition. NK cells also produce cytokines such as IFN-gamma (IFN-gamma)
      to protect the host during the innate response to infection. Herein, we show that
      cytokine-activated NK cells transferred into naive hosts can be specifically
      detected 7-22 days later when they are phenotypically similar to naive cells and
      are not constitutively producing IFN-gamma. However, they produce significantly
      more IFN-gamma when restimulated. This memory-like property is intrinsic to the
      NK cell. By contrast, memory-like NK cells do not express granzyme B protein and
      kill targets similarly to naive NK cells. Thus, these experiments identify an
      ability of innate immune cells to retain an intrinsic memory of prior activation,
      a function until now attributed only to antigen-specific adaptive immune cells.

PMID- 19181845
TI  - Guanylyl cyclase-D in the olfactory CO2 neurons is activated by bicarbonate.
AB  - Atmospheric CO(2) is an important environmental cue that regulates several types
      of animal behavior. In mice, CO(2) responses of the olfactory sensory neurons
      (OSNs) require the activity of carbonic anhydrase to catalyze the conversion of
      CO(2) to bicarbonate and the opening of cGMP-sensitive ion channels. However, it
      remains unknown how the enhancement of bicarbonate levels results in cGMP
      production. Here, we show that bicarbonate activates cGMP-producing ability of
      guanylyl cyclase-D (GC-D), a membrane GC exclusively expressed in the CO(2)
      responsive OSNs, by directly acting on the intracellular cyclase domain of GC-D.
      Also, the molecular mechanism for GC-D activation is distinct from the commonly
      believed model of "release from repression" for other membrane GCs. Our results
      contribute to our understanding of the molecular mechanisms of CO(2) sensing and
      suggest diverse mechanisms of molecular activation among membrane GCs.

PMID- 19181846
TI  - E2A proteins maintain the hematopoietic stem cell pool and promote the maturation
      of myelolymphoid and myeloerythroid progenitors.
AB  - Hematopoiesis is a tightly controlled process maintained by a small pool of
      hematopoietic stem cells (HSCs). Here, we demonstrate that the LT-HSC, MPP,
      premegakaryocytic/erythroid, Pre CFU-E, Pre GM, MkP, and granulocyte-macrophage
      compartments were all significantly reduced in E2A-deficient bone marrow. Despite
      a severe depletion of erythroid progenitors, the erythrocyte and megakaryocyte
      compartments were equivalent in E2A-deficient bone marrow as compared with wild
      type mice. E2A-deficient HSCs also failed to efficiently maintain the HSC pool on
      serial transplantation, and we demonstrate that the E2A proteins regulate cell
      cycle progression of HSCs by regulating the expression of p21(Cip1), p27(Kip1),
      and the thrombopoietin receptor, known regulators of HSC self-renewal activity.
      Based on these observations, we propose that the E2A proteins promote the
      developmental progression of the entire spectrum of early hematopoietic
      progenitors and to suppress an erythroid specific program of gene expression in
      alternative cell lineages. Last, the data mechanistically link E2A, cell cycle
      regulators, and the maintenance of the HSC pool in a common pathway.

PMID- 19181847
TI  - The cavity-chaperone Skp protects its substrate from aggregation but allows
      independent folding of substrate domains.
AB  - Outer membrane proteins (OMPs) of gram-negative bacteria are synthesized in the
      cytosol and must cross the periplasm before insertion into the outer membrane.
      The 17-kDa protein (Skp) is a periplasmic chaperone that assists the folding and
      insertion of many OMPs, including OmpA, a model OMP with a membrane embedded beta
      barrel domain and a periplasmic alphabeta domain. Structurally, Skp belongs to a
      family of cavity-containing chaperones that bind their substrates in the cavity,
      protecting them from aggregation. However, some substrates, such as OmpA, exceed
      the capacity of the chaperone cavity, posing a mechanistic challenge. Here, we
      provide direct NMR evidence that, while bound to Skp, the beta-barrel domain of
      OmpA is maintained in an unfolded state, whereas the periplasmic domain is folded
      in its native conformation. Complementary cross-linking and NMR relaxation
      experiments show that the OmpA beta-barrel is bound deep within the Skp cavity,
      whereas the folded periplasmic domain protrudes outside of the cavity where it
      tumbles independently from the rest of the complex. This domain-based chaperoning
      mechanism allows the transport of beta-barrels across the periplasm in an
      unfolded state, which may be important for efficient insertion into the outer
      membrane.

PMID- 19181848
TI  - Type III restriction enzymes communicate in 1D without looping between their
      target sites.
AB  - To cleave DNA, Type III restriction enzymes must communicate the relative
      orientation of two asymmetric recognition sites over hundreds of base pairs. The
      basis of this long-distance communication, for which ATP hydrolysis by their
      helicase domains is required, is poorly understood. Several conflicting DNA
      looping mechanisms have been proposed, driven either by active DNA translocation
      or passive 3D diffusion. Using single-molecule DNA stretching in combination with
      bulk-solution assays, we provide evidence that looping is both highly unlikely
      and unnecessary, and that communication is strictly confined to a 1D route.
      Integrating our results with previous data, a simple communication scheme is
      concluded based on 1D diffusion along DNA.

PMID- 19181849
TI  - Electrostatic effects on funneled landscapes and structural diversity in
      denatured protein ensembles.
AB  - The denatured state of proteins is heterogeneous and susceptible to general
      hydrophobic and electrostatic forces, but to what extent does the funneled nature
      of protein energy landscapes play a role in the unfolded ensemble? We simulate
      the denatured ensemble of cytochrome c using a series of models. The models
      pinpoint the efficacy of incorporating energetic funnels toward the native state
      in contrast with models having no native structure-seeking tendency. These models
      also contain varying strengths of electrostatic effects and hydrophobic collapse.
      The simulations based on these models are compared with experimental
      distributions for the distances between a fluorescent donor and the heme acceptor
      that were extracted from time-resolved fluorescence energy transfer experiments
      on cytochrome c. Comparing simulations to detailed experimental data on several
      labeling sites allows us to quantify the dominant forces in denatured protein
      ensembles.

PMID- 19181843
TI  - Gene-centric metagenomics of the fiber-adherent bovine rumen microbiome reveals
      forage specific glycoside hydrolases.
AB  - The complex microbiome of the rumen functions as an effective system for the
      conversion of plant cell wall biomass to microbial protein, short chain fatty
      acids, and gases. As such, it provides a unique genetic resource for plant cell
      wall degrading microbial enzymes that could be used in the production of
      biofuels. The rumen and gastrointestinal tract harbor a dense and complex
      microbiome. To gain a greater understanding of the ecology and metabolic
      potential of this microbiome, we used comparative metagenomics (phylotype
      analysis and SEED subsystems-based annotations) to examine randomly sampled
      pyrosequence data from 3 fiber-adherent microbiomes and 1 pooled liquid sample (a
      mixture of the liquid microbiome fractions from the same bovine rumens). Even
      though the 3 animals were fed the same diet, the community structure, predicted
      phylotype, and metabolic potentials in the rumen were markedly different with
      respect to nutrient utilization. A comparison of the glycoside hydrolase and
      cellulosome functional genes revealed that in the rumen microbiome, initial
      colonization of fiber appears to be by organisms possessing enzymes that attack
      the easily available side chains of complex plant polysaccharides and not the
      more recalcitrant main chains, especially cellulose. Furthermore, when compared
      with the termite hindgut microbiome, there are fundamental differences in the
      glycoside hydrolase content that appear to be diet driven for either the bovine
      rumen (forages and legumes) or the termite hindgut (wood).

PMID- 19181850
TI  - The Drosophila modigliani (moi) gene encodes a HOAP-interacting protein required
      for telomere protection.
AB  - Several proteins have been identified that protect Drosophila telomeres from
      fusion events. They include UbcD1, HP1, HOAP, the components of the Mre11-Rad50
      Nbs (MRN) complex, the ATM kinase, and the putative transcription factor Woc. Of
      these proteins, only HOAP has been shown to localize specifically at telomeres.
      Here we show that the modigliani gene encodes a protein (Moi) that is enriched
      only at telomeres, colocalizes and physically interacts with HOAP, and is
      required to prevent telomeric fusions. Moi is encoded by the bicistronic CG31241
      locus. This locus produces a single transcript that contains 2 ORFs that specify
      different essential functions. One of these ORFs encodes the 20-kDa Moi protein.
      The other encodes a 60-kDa protein homologous to RNA methyltransferases that is
      not required for telomere protection (Drosophila Tat-like). Moi and HOAP share
      several properties with the components of shelterin, the protein complex that
      protects human telomeres. HOAP and Moi are not evolutionarily conserved unlike
      the other proteins implicated in Drosophila telomere protection. Similarly, none
      of the shelterin subunits is conserved in Drosophila, while most human
      nonshelterin proteins have Drosophila homologues. This suggests that the HOAP-Moi
      complex, we name "terminin," plays a specific role in the DNA sequence
      independent assembly of Drosophila telomeres. We speculate that this complex is
      functionally analogous to shelterin, which binds chromosome ends in a sequence
      dependent manner.

PMID- 19181852
TI  - Direct quantification of polo-like kinase 1 activity in cells and tissues using a
      highly sensitive and specific ELISA assay.
AB  - Polo-like kinase 1 (Plk1) plays a pivotal role in the regulation of cellular
      proliferation. Plk1 is overexpressed in approximately 80% of human tumors of
      diverse origins, and overexpression of Plk1 promotes neoplastic transformation of
      human cells. A growing body of evidence suggests that deregulation of Plk1
      closely correlates with prognosis of various cancers in humans. Thus, accurate
      assessment of Plk1 deregulation would provide clear clinical advantages. However,
      because of the limited amount of cancer tissues available, quantification of the
      Plk1 activity has not been feasible. Here, we report the development of a rapid,
      highly sensitive, and specific ELISA-based Plk1 assay that can quantify the level
      of Plk1 activity with a small amount (2-20 microg) of total cellular proteins.
      Unlike the conventional immunocomplex kinase assay, this assay directly utilizes
      total cellular lysates and does not require a Plk1 enrichment step such as
      immunoprecipitation or affinity purification. Using this assay, we demonstrated
      that Plk1 activity is elevated in tumors but not in the surrounding normal
      tissues and that the level of Plk1 activity significantly diminishes after an
      antiproliferative chemotherapy. The method described here may provide an
      innovative tool for assessing the predisposition for cancer development,
      monitoring early tumor response after therapy, and estimating the prognosis of
      patients with cancers from multiple organ sites.

PMID- 19181851
TI  - Explosive Pleistocene diversification and hemispheric expansion of a "great
      speciator".
AB  - Factors that influence speciation rates among groups of organisms are integral to
      deciphering macroevolutionary processes; however, they remain poorly understood.
      Here, we use molecular phylogenetic data and divergence time estimates to
      reconstruct the pattern and tempo of speciation within a widespread and
      homogeneous bird family (white-eyes, Zosteropidae) that contains an archetypal
      "great speciator." Our analyses show that the majority of this species-rich
      family constitutes a clade that arose within the last 2 million years, yielding a
      per-lineage diversification rate among the highest reported for vertebrates (1.95
      2.63 species per million years). However, unlike most rapid radiations reported
      to date, this burst of diversification was not limited in geographic scope, but
      instead spanned the entire Old World tropics, parts of temperate Asia, and
      numerous Atlantic, Pacific, and Indian Ocean archipelagos. The tempo and
      geographic breadth of this rapid radiation defy any single diversification
      paradigm, but implicate a prominent role for lineage-specific life-history traits
      (such as rapid evolutionary shifts in dispersal ability) that enabled white-eyes
      to respond rapidly and persistently to the geographic drivers of diversification.

PMID- 19181853
TI  - Ppp1r15 gene knockout reveals an essential role for translation initiation factor
      2 alpha (eIF2alpha) dephosphorylation in mammalian development.
AB  - Diverse cellular stress responses are linked to phosphorylation of serine 51 on
      the alpha subunit of translation initiation factor 2. The resultant attenuation
      of protein synthesis and activation of gene expression figure heavily in the
      adaptive response to stress, but dephosphorylation of eIF2(alphaP), which
      terminates signaling in this pathway, is less well understood. GADD34 and CReP,
      the products of the related mammalian genes Ppp1r15a and Ppp1r15b, can recruit
      phosphatase catalytic subunits of the PPP1 class to eIF2(alphaP), but the
      significance of their contribution to its dephosphorylation has not been explored
      systematically. Here we report that unlike Ppp1r15a mutant mice, which are
      superficially indistinguishable from wild type, Ppp1r15b(-/-) mouse embryos
      survive gestation but exhibit severe growth retardation and impaired
      erythropoiesis, and loss of both Ppp1r15 genes leads to early embryonic
      lethality. These loss-of-function phenotypes are rescued by a mutation,
      Eif2a(S51A), that prevents regulated phosphorylation of eIF2alpha. These findings
      reveal that the essential process of eIF2(alphaP) dephosphorylation is the
      predominant role of PPP1R15 proteins in mammalian development.

PMID- 19181854
TI  - Detergent binding explains anomalous SDS-PAGE migration of membrane proteins.
AB  - Migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
      that does not correlate with formula molecular weights, termed "gel shifting,"
      appears to be common for membrane proteins but has yet to be conclusively
      explained. In the present work, we investigate the anomalous gel mobility of
      helical membrane proteins using a library of wild-type and mutant helix-loop
      helix ("hairpin") sequences derived from transmembrane segments 3 and 4 of the
      human cystic fibrosis transmembrane conductance regulator (CFTR), including
      disease-phenotypic residue substitutions. We find that these hairpins migrate at
      rates of -10% to +30% vs. their actual formula weights on SDS-PAGE and load
      detergent at ratios ranging from 3.4-10 g SDS/g protein. We additionally
      demonstrate that mutant gel shifts strongly correlate with changes in hairpin SDS
      loading capacity (R(2) = 0.8), and with hairpin helicity (R(2) = 0.9), indicating
      that gel shift behavior originates in altered detergent binding. In some cases,
      this differential solvation by SDS may result from replacing protein-detergent
      contacts with protein-protein contacts, implying that detergent binding and
      folding are intimately linked. The CF-phenotypic V232D mutant included in our
      library may thus disrupt CFTR function via altered protein-lipid interactions.
      The observed interdependence between hairpin migration, SDS aggregation number,
      and conformation additionally suggests that detergent binding may provide a rapid
      and economical screen for identifying membrane proteins with robust tertiary
      and/or quaternary structures.

PMID- 19181855
TI  - Tissue plasminogen activator modulates the cellular and behavioral response to
      cocaine.
AB  - Cocaine exposure induces long-lasting molecular and structural adaptations in the
      brain. In this study, we show that tissue plasminogen activator (tPA), an
      extracellular protease involved in neuronal plasticity, modulates the biochemical
      and behavioral response to cocaine. When injected in the acute binge paradigm,
      cocaine enhanced tPA activity in the amygdala, which required activation of
      corticotropin-releasing factor type-1 (CRF-R1) receptors. Compared with WT mice,
      tPA-/- mice injected with cocaine displayed attenuated phosphorylation of ERK,
      cAMP response element binding protein (CREB), and dopamine and cAMP-regulated
      phosphoprotein 32 kDa (DARPP-32) and blunted induction of immediate early genes
      (IEGs) c-Fos, Egr-1, and Homer 1a in the amygdala and the nucleus accumbens
      (NAc). tPA-/- mice also displayed significantly higher basal preprodynorphin
      (ppDyn) mRNA levels in the NAc in comparison to WT mice, and cocaine decreased
      ppDyn mRNA levels in tPA-/- mice only. Cocaine-induced locomotor sensitization
      and conditioned place preference (CPP) were attenuated in tPA-/- mice. Cocaine
      exposure also had an anxiolytic effect in tPA-/- but not WT mice. These results
      identify tPA as an important and novel component of the signaling pathway that
      modulates cocaine-induced changes in neuroadaptation and behavior.

PMID- 19181856
TI  - Large-scale detection of ubiquitination substrates using cell extracts and
      protein microarrays.
AB  - Identification of protein targets of post-translational modification is an
      important analytical problem in biology. Protein microarrays exposed to cellular
      extracts could offer a rapid and convenient means of identifying modified
      proteins, but this kind of biochemical assay, unlike DNA microarrays, depends on
      a faithful reconstruction of in vivo conditions. Over several years, concentrated
      cellular extracts have been developed, principally for cell cycle studies that
      reproduce very complex cellular states. We have used extracts that replicate the
      mitotic checkpoint and anaphase release to identify differentially regulated
      poyubiquitination. Protein microarrays were exposed to these complex extracts,
      and the polyubiquitinated products were detected by specific antibodies. We
      expected that among the substrates revealed by the microarray should be
      substrates of the anaphase promoting complex (APC). Among 8,000 proteins on the
      chip, 10% were polyubiquitinated. Among those, we found 11 known APC substrates
      (out of 16 present on the chip) to be polyubiquitinated. Interestingly, only 1.5%
      of the proteins were differentially ubiquitinated on exit from the checkpoint.
      When we arbitrarily chose 6 proteins thought to be involved in mitosis from the
      group of differentially modified proteins, all registered as putative substrates
      of the APC, and among 4 arbitrarily chosen non-mitotic proteins picked from the
      same list, 2 were ubiquitinated in an APC-dependent manner. The striking yield of
      potential APC substrates from a simple assay with concentrated cell extracts
      suggests that combining microarray analysis of the products of post-translational
      modifications with extracts that preserve the physiological state of the cell can
      yield information on protein modification under various in vivo conditions.

PMID- 19181857
TI  - Protection from lethal gram-negative bacterial sepsis by targeting Toll-like
      receptor 4.
AB  - Toll-like receptor 4 (TLR4), the signal-transducing molecule of the LPS receptor
      complex, plays a fundamental role in the sensing of LPS from gram-negative
      bacteria. Activation of TLR4 signaling pathways by LPS is a critical upstream
      event in the pathogenesis of gram-negative sepsis, making TLR4 an attractive
      target for novel antisepsis therapy. To validate the concept of TLR4-targeted
      treatment strategies in gram-negative sepsis, we first showed that TLR4(-/-) and
      myeloid differentiation primary response gene 88 (MyD88)(-/-) mice were fully
      resistant to Escherichia coli-induced septic shock, whereas TLR2(-/-) and wild
      type mice rapidly died of fulminant sepsis. Neutralizing anti-TLR4 antibodies
      were then generated using a soluble chimeric fusion protein composed of the N
      terminal domain of mouse TLR4 (amino acids 1-334) and the Fc portion of human
      IgG1. Anti-TLR4 antibodies inhibited intracellular signaling, markedly reduced
      cytokine production, and protected mice from lethal endotoxic shock and E. coli
      sepsis when administered in a prophylactic and therapeutic manner up to 13 h
      after the onset of bacterial sepsis. These experimental data provide strong
      support for the concept of TLR4-targeted therapy for gram-negative sepsis.

PMID- 19181858
TI  - Genome-wide suppression of aberrant mRNA-like noncoding RNAs by NMD in
      Arabidopsis.
AB  - The nonsense-mediated mRNA decay (NMD) pathway is a well-known eukaryotic
      surveillance mechanism that eliminates aberrant mRNAs that contain a premature
      termination codon (PTC). The UP-Frameshift (UPF) proteins, UPF1, UPF2, and UPF3,
      are essential for normal NMD function. Several NMD substrates have been
      identified, but detailed information on NMD substrates is lacking. Here, we
      noticed that, in Arabidopsis, most of the mRNA-like nonprotein-coding RNAs
      (ncRNAs) have the features of an NMD substrate. We examined the expression
      profiles of 2 Arabidopsis mutants, upf1-1 and upf3-1, using a whole-genome tiling
      array. The results showed that expression of not only protein-coding transcripts
      but also many mRNA-like ncRNAs (mlncRNAs), including natural antisense transcript
      RNAs (nat-RNAs) transcribed from the opposite strands of the coding strands, were
      up-regulated in both mutants. The percentage of the up-regulated mlncRNAs to all
      expressed mlncRNAs was much higher than that of the up-regulated protein-coding
      transcripts to all expressed protein- coding transcripts. This finding
      demonstrates that one of the most important roles of NMD is the genome-wide
      suppression of the aberrant mlncRNAs including nat-RNAs.

PMID- 19181859
TI  - Molecular recognition and self-assembly special feature: Encapsulation and
      characterization of proton-bound amine homodimers in a water-soluble, self
      assembled supramolecular host.
AB  - Cyclic amines can be encapsulated in a water-soluble self-assembled
      supramolecular host upon protonation. The hydrogen-bonding ability of the cyclic
      amines, as well as the reduced degrees of rotational freedom, allows for the
      formation of proton-bound homodimers inside of the assembly that are otherwise
      not observable in aqueous solution. The generality of homodimer formation was
      explored with small N-alkyl aziridines, azetidines, pyrrolidines, and
      piperidines. Proton-bound homodimer formation is observed for N-alkylaziridines
      (R = methyl, isopropyl, tert-butyl), N-alkylazetidines (R = isopropyl, tert
      butyl), and N-methylpyrrolidine. At high concentration, formation of a proton
      bound homotrimer is observed in the case of N-methylaziridine. The homodimers
      stay intact inside the assembly over a large concentration range, thereby
      suggesting cooperative encapsulation. Both G3(MP2)B3 and G3B3 calculations of the
      proton-bound homodimers were used to investigate the enthalpy of the hydrogen
      bond in the proton-bound homodimers and suggest that the enthalpic gain upon
      formation of the proton-bound homodimers may drive guest encapsulation.

PMID- 19181860
TI  - Transcriptome-guided characterization of genomic rearrangements in a breast
      cancer cell line.
AB  - We have identified new genomic alterations in the breast cancer cell line
      HCC1954, using high-throughput transcriptome sequencing. With 120 Mb of cDNA
      sequences, we were able to identify genomic rearrangement events leading to
      fusions or truncations of genes including MRE11 and NSD1, genes already
      implicated in oncogenesis, and 7 rearrangements involving other additional genes.
      This approach demonstrates that high-throughput transcriptome sequencing is an
      effective strategy for the characterization of genomic rearrangements in cancers.

PMID- 19181861
TI  - Regulation of Cyclin A protein in meiosis and early embryogenesis.
AB  - In contrast to the extensive analysis of the regulation of Cyclin B protein
      levels during developmental progression through meiosis in oogenesis, little is
      known about Cyclin A. Repression of cyclin A translation early in prophase I in
      Drosophila is important to maintain the oocyte in meiosis, and this has been
      shown to be mediated by deadenylation of the mRNA and inhibition by the Bruno
      repressor. We find that at oocyte maturation as meiosis resumes, Cyclin A protein
      reappears, coincident with polyadenylation of the mRNA and loss of Bruno
      repressor. Cyclin A is multiphosphorylated in a pattern consistent with
      autophosphorylation, and this form accumulates aberrantly in metaphase I if the
      Cortex form of the Anaphase Promoting Complex/Cyclosome is inactive. The PAN GU
      (PNG) kinase positively promotes translation of Cyclin A, beginning in oogenesis,
      an earlier onset than previously recognized. After egg activation and the
      completion of meiosis, PNG promotes further polyadenylation of cyclin A mRNA and
      appears to antagonize repression of translation by the PUMILIO inhibitor.
      Epistasis studies with png; apc mutants indicate that PNG acts solely to promote
      translation, rather than having a parallel function to inhibit degradation. These
      studies reveal multiple levels of posttranscriptional regulation of Cyclin A
      protein by translational and proteolytic control during oocyte maturation and the
      onset of embryogenesis.

PMID- 19181862
TI  - Signals in bacterial beta-barrel proteins are functional in eukaryotic cells for
      targeting to and assembly in mitochondria.
AB  - The outer membranes of Gram-negative bacteria, mitochondria, and chloroplasts
      harbor beta-barrel proteins. The signals that allow precursors of such proteins
      to be targeted to mitochondria were not characterized so far. To better
      understand the mechanism by which beta-barrel precursor proteins are recognized
      and sorted within eukaryotic cells, we expressed the bacterial beta-barrel
      proteins PhoE, OmpA, Omp85, and OmpC in Saccharomyces cerevisiae and demonstrated
      that they were imported into mitochondria. A detailed investigation of the import
      pathway of PhoE revealed that it is shared with mitochondrial beta-barrel
      proteins. PhoE interacts initially with surface import receptors, and its further
      sorting depends on components of the TOB/SAM complex. The bacterial Omp85 and
      PhoE integrated into the mitochondrial outer membrane as native-like oligomers.
      For the latter protein this assembly depended on the C-terminal Phe residue,
      which is important also for the correct assembly of PhoE into the bacterial outer
      membrane. Collectively, it appears that mitochondrial beta-barrel proteins have
      not evolved eukaryotic-specific signals to ensure their import into mitochondria.
      Furthermore, the signal for assembly of beta-barrel proteins into the bacterial
      outer membrane is functional in mitochondria.

PMID- 19181863
TI  - The generation and properties of human macrophage populations from hemopoietic
      stem cells.
AB  - Information about the development and function of human macrophage lineage
      populations, such as osteoclasts, is limited because of the lack of defined in
      vitro systems for their large-scale generation. Two M-CSF-containing cytokine
      cocktails were found under serum-free conditions to expand dramatically and to
      differentiate over time human CD34(+) hemopoietic stem cells into nonadherent and
      adherent macrophage populations. These populations exhibited increasing degrees
      of maturity over a 3-week period characterized by morphology, surface marker
      expression (CD11b, CD86, CD64, CD14, and c-Fms), phagocytic function, and gene
      expression profiling using quantitative PCR and microarray analysis (principal
      component analysis, k-means clustering, and gene ontology classification). As
      assessed by the last criterion, the adherent population obtained at 3 weeks from
      the one protocol tested had high similarity to the well-studied peripheral blood
      monocyte-derived macrophages. The one population tested could be induced to
      differentiate into osteoclasts in the presence of M-CSF and receptor activator of
      NF-kappaB ligand, as judged by morphology, gene expression, and bone-resorbing
      ability. In addition to the large numbers of macrophage lineage cells able to be
      produced, this replicating system may be suitable for the molecular analysis of
      macrophage lineage commitment and progression and for gene targeting and
      delivery.

PMID- 19181864
TI  - Heterologous expression analyses of rice OsCAS in Arabidopsis and in yeast
      provide evidence for its roles in cyanide detoxification rather than in cysteine
      synthesis in vivo.
AB  - While most dicot plants produce little ethylene in their vegetative stage, many
      monocots such as rice liberate a relatively large amount of ethylene with cyanide
      as a co-product in their seedling stage when etiolated. One of the known
      functions of beta-cyanoalanine synthase (CAS) is to detoxify the co-product
      cyanide during ethylene biosynthesis in higher plants. Based on a tryptic peptide
      sequence obtained from a partially purified CAS activity protein preparation in
      etiolated rice seedlings, the full-length putative rice CAS-encoding cDNA
      sequence (OsCAS), which is homologous to those O-acetylserine sulphydrylase
      (OASS) genes, was cloned. Unlike most of the CAS genes reported from dicots, the
      transcription of OsCAS is promoted by auxins but suppressed by ethylene. To
      address the function and the subcellular localization of this gene product in
      planta, a binary vector construct consisting of this gene appended with a yellow
      fluorescent protein-encoding sequence was employed to transform Arabidopsis.
      Specific activities on CAS and OASS of the purified recombinant protein from
      transgenic Arabidopsis were 181.04 micromol H(2)S mg(-1) protein min(-1) and 0.92
      micromol Cys mg(-1) protein min(-1), respectively, indicating that OsCAS favours
      CAS activity. The subcellular localization of OsCAS was found mostly in the
      mitochondria by immunogold electron-microscopy. Chemical cross-linking and in-gel
      assay on a heterodimer composed of functional and non-functional mutants in a
      yeast expression system on OsCAS suggested that OsCAS functions as a homodimer,
      similar to that of OASS. Despite the structural similarity of OsCAS with OASS, it
      has also been confirmed that OsCAS could not interact with serine
      acetyltransferase, indicating that OsCAS mainly functions in cyanide
      detoxification.

PMID- 19181866
TI  - The guard cell as a single-cell model towards understanding drought tolerance and
      abscisic acid action.
AB  - Stomatal guard cells are functionally specialized epidermal cells usually
      arranged in pairs surrounding a pore. Changes in ion fluxes, and more
      specifically osmolytes, within the guard cells drive opening/closing of the pore,
      allowing gas exchange while limiting water loss through evapo-transpiration.
      Adjustments of the pore aperture to optimize these conflicting needs are thus
      centrally important for land plants to survive, especially with the rise in CO(2)
      associated with global warming and increasing water scarcity this century. The
      basic biophysical events in modulating membrane transport have been gradually
      delineated over two decades. Genetics and molecular approaches in recent years
      have complemented and extended these earlier studies to identify major regulatory
      nodes. In Arabidopsis, the reference for guard cell genetics, stomatal opening
      driven by K(+) entry is mainly through KAT1 and KAT2, two voltage-gated K(+)
      inward-rectifying channels that are activated on hyperpolarization of the plasma
      membrane principally by the OST2 H(+)-ATPase (proton pump coupled to ATP
      hydrolysis). By contrast, stomatal closing is caused by K(+) efflux mainly
      through GORK, the outward-rectifying channel activated by membrane
      depolarization. The depolarization is most likely initiated by SLAC1, an anion
      channel distantly related to the dicarboxylate/malic acid transport protein found
      in fungi and bacteria. Beyond this established framework, there is also
      burgeoning evidence for the involvement of additional transporters, such as
      homologues to the multi-drug resistance proteins (or ABC transporters) as
      intimated by several pharmacological and reverse genetics studies. General
      inhibitors of protein kinases and protein phosphatases have been shown to
      profoundly affect guard cell membrane transport properties. Indeed, the first
      regulatory enzymes underpinning these transport processes revealed genetically
      were several protein phosphatases of the 2C class and the OST1 kinase, a member
      of the SnRK2 family. Taken together, these results are providing the first
      glimpses of an emerging signalling complex critical for modulating the stomatal
      aperture in response to environmental stimuli.

PMID- 19181865
TI  - Sucrose transporter1 functions in phloem loading in maize leaves.
AB  - In most plants, sucrose is exported from source leaves to carbon-importing sink
      tissues to sustain their growth and metabolism. Apoplastic phloem-loading species
      require sucrose transporters (SUTs) to transport sucrose into the phloem. In many
      dicot plants, genetic and biochemical evidence has established that SUT1-type
      proteins function in phloem loading. However, the role of SUT1 in phloem loading
      in monocot plants is not clear since the rice (Oryza sativa) and sugarcane
      (Saccharum hybrid) SUT1 orthologues do not appear to function in phloem loading
      of sucrose. A SUT1 gene was previously cloned from maize (Zea mays) and shown to
      have expression and biochemical activity consistent with a hypothesized role in
      phloem loading. To determine the biological function of SUT1 in maize, a sut1
      mutant was isolated and characterized. sut1 mutant plants hyperaccumulate
      carbohydrates in mature leaves and display leaf chlorosis with premature
      senescence. In addition, sut1 mutants have greatly reduced stature, altered
      biomass partitioning, delayed flowering, and stunted tassel development. Cold
      girdling wild-type leaves to block phloem transport phenocopied the sut1 mutants,
      supporting a role for maize SUT1 in sucrose export. Furthermore, application of
      (14)C-sucrose to abraded sut1 mutant and wild-type leaves showed that sucrose
      export was greatly diminished in sut1 mutants compared with wild type.
      Collectively, these data demonstrate that SUT1 is crucial for efficient phloem
      loading of sucrose in maize leaves.

PMID- 19181867
TI  - Provocation of silence.
AB  - We describe the development of a Brugada ECG together with sinus- and ventricular
      arrest after intravenous flecainide for atrial fibrillation in a patient in whom
      eventually a SCN5a mutation was identified. Unrecognized SCN5A mutations could
      underlie class IC-induced sinus arrest and conduction defects in some patients.

PMID- 19181868
TI  - Does a healthy diet help weight management among overweight and obese people?
AB  - A randomized dietary intervention trial across 4 years examined diet, weight, and
      obesity incidence (body mass index [BMI] > or = 30 kg/m(2)) differences between
      study groups. Participants were 1,510 breast cancer survivors with BMI > or = 25
      kg/m(2) at entry. Dietary intake was assessed yearly by telephone; weight and
      height were measured at clinic visits. Intervention participants consumed more
      fruit, vegetables, and fiber and less energy from fat than control participants
      during follow-up cross-sectionally (p < .0001) and longitudinally (p < .0001);
      weight did not differ between study groups at any follow-up visit, and
      significant weight change difference was observed between groups only in the 1st
      year (p < .0001). Diet and weight results remained unchanged after stratifying by
      age and BMI. No difference in obesity incidence was found during follow-up (p >
      .10) among overweight members of either study group. Without specific efforts to
      reduce total energy intake, dietary modification does not reduce obesity or
      result in long-term weight loss.

PMID- 19181869
TI  - Disruption of Plasmodium sporozoite transmission by depletion of sporozoite
      invasion-associated protein 1.
AB  - Accumulation of infectious Plasmodium sporozoites in Anopheles spp. salivary
      glands marks the final step of the complex development of the malaria parasite in
      the insect vector. Sporozoites are formed inside midgut-associated oocysts and
      actively egress into the mosquito hemocoel. Traversal of the salivary gland
      acinar cells correlates with the sporozoite's capacity to perform continuous
      gliding motility. Here, we characterized the cellular role of the Plasmodium
      berghei sporozoite invasion-associated protein 1 (SIAP-1). Intriguingly, SIAP-1
      orthologs are found exclusively in apicomplexan hemoprotozoa, parasites that are
      transmitted by arthropod vectors, e.g., Plasmodium, Babesia, and Theileria
      species. By fluorescent tagging with mCherry, we show that SIAP-1 is expressed in
      oocyst-derived and salivary gland-associated sporozoites, where it accumulates at
      the apical tip. Targeted disruption of SIAP-1 does not affect sporozoite
      formation but causes a partial defect in sporozoite egress from oocysts and
      abolishes sporozoite colonization of mosquito salivary glands. Parasites with the
      siap-1(-) mutation are blocked in their capacity to perform continuous gliding
      motility. We propose that arthropod-transmitted apicomplexan parasites
      specifically express secretory factors, such as SIAP-1, that mediate efficient
      oocyst exit and migration to the salivary glands.

PMID- 19181870
TI  - HacA-dependent transcriptional switch releases hacA mRNA from a translational
      block upon endoplasmic reticulum stress.
AB  - Activation of the unfolded protein response (UPR) in eukaryotes involves the
      splicing of an unconventional intron from the mRNA encoding the transcriptional
      activator of the pathway. In Saccharomyces cerevisiae a 252-nucleotide (nt)
      unconventional intron is spliced out of the transcript of HAC1, changing the 3'
      end of the HAC1 open reading frame and relieving the transcript from a
      translational block in a single step. The translational block is caused by the
      base pairing of part of the unconventional intron with the 5'-untranslated region
      (5'UTR). In Aspergillus niger and other aspergilli, the unconventional intron in
      hacA mRNA is only 20 nt long. Since this intron is part of a stable stem-loop
      structure, base pairing with the 5'UTR, in contrast to the case with yeast HAC1,
      is not possible. However, analysis of the hacA mRNA revealed a GC-rich inverted
      repeat (18 base pairings). Upon the activation of the UPR, the 5'UTR of hacA mRNA
      is truncated by 230 nt, removing the left part of this inverted repeat. This
      implies a similar release of a translational block as in the case of S.
      cerevisiae HAC1 but in two steps. The mechanism behind the 5' truncation, which
      does not take place in either yeast HAC1 or mammalian xbp1 mRNA, has been
      hitherto unknown. Here we show that during secretion stress in A. niger, hacA
      transcription starts from a new start site closer to the ATG, relieving the
      transcript from translational attenuation. This transcriptional switch is
      mediated by HacA itself and the unfolded protein response element 2 (UPRE2) in
      the hacA promoter.

PMID- 19181871
TI  - Identification and specific localization of tyrosine-phosphorylated proteins in
      Trypanosoma brucei.
AB  - Phosphorylation on tyrosine residues is a key signal transduction mechanism known
      to regulate intercellular and intracellular communication in multicellular
      organisms. Despite the lack of conventional tyrosine kinases in the genome of the
      single cell organism Trypanosoma brucei, phosphorylation on trypanosomal protein
      tyrosine residues has been reported for this parasite. However, the identities of
      most of the tyrosine-phosphorylated proteins and their precise site(s) of
      phosphorylation were unknown. Here, we have applied a phosphotyrosine-specific
      proteomics approach to identify 34 phosphotyrosine-containing proteins from whole
      cell extracts of procyclic form T. brucei. A significant proportion of the
      phosphotyrosine-containing proteins identified in this study were protein kinases
      of the CMGC kinase group as well as some proteins of unknown function and
      proteins involved in energy metabolism, protein synthesis, and RNA metabolism.
      Interestingly, immunofluorescence microscopy using anti-phosphotyrosine
      antibodies suggests that there is a concentration of tyrosine-phosphorylated
      proteins associated with cytoskeletal structures (basal body and flagellum) and
      in the nucleolus of the parasite. This localization of tyrosine-phosphorylated
      proteins supports the idea that the function of signaling molecules is controlled
      by their precise location in T. brucei, a principle well known from higher
      eukaryotes.

PMID- 19181872
TI  - Analysis of all protein phosphatase genes in Aspergillus nidulans identifies a
      new mitotic regulator, fcp1.
AB  - Reversible protein phosphorylation is an important regulatory mechanism of cell
      cycle control in which protein phosphatases counteract the activities of protein
      kinases. In Aspergillus nidulans, 28 protein phosphatase catalytic subunit genes
      were identified. Systematic deletion analysis identified four essential
      phosphatases and four required for normal growth. Conditional alleles of these
      were generated using the alcA promoter. The deleted phosphatase strain collection
      and regulatable versions of the essential and near-essential phosphatases provide
      an important resource for further analysis of the role of reversible protein
      phosphorylation to the biology of A. nidulans. We further demonstrate that nimT
      and bimG have essential functions required for mitotic progression since their
      deletions led to classical G(2)- and M-phase arrest. Although not as obvious,
      cells with AnpphA and Annem1 deleted also have mitotic abnormalities. One of the
      essential phosphatases, the RNA polymerase II C-terminal domain phosphatase
      Anfcp1, was further examined for potential functions in mitosis because a
      temperature-sensitive Anfcp1 allele was isolated in a genetic screen showing
      synthetic interaction with the cdk1F mutation, a hyperactive mitotic kinase. The
      Anfcp1(ts) cdk1F double mutant had severe mitotic defects, including inability of
      nuclei to complete mitosis in a normal fashion. The severity of the Anfcp1(ts)
      cdk1F mitotic phenotypes were far greater than either single mutant, confirming
      the synthetic nature of their genetic interaction. The mitotic defects of the
      Anfcp1(ts) cdk1F double mutant suggests a previously unrealized function for
      AnFCP1 in regulating mitotic progression, perhaps counteracting Cdk1-mediated
      phosphorylation.

PMID- 19181873
TI  - Isolation and characterization of Cryptococcus neoformans spores reveal a
      critical role for capsule biosynthesis genes in spore biogenesis.
AB  - Spores are essential particles for the survival of many organisms, both
      prokaryotic and eukaryotic. Among the eukaryotes, fungi have developed spores
      with superior resistance and dispersal properties. For the human fungal
      pathogens, however, relatively little is known about the role that spores play in
      dispersal and infection. Here we present the purification and characterization of
      spores from the environmental fungus Cryptococcus neoformans. For the first time,
      we purified spores to homogeneity and assessed their morphological, stress
      resistance, and surface properties. We found that spores are morphologically
      distinct from yeast cells and are covered with a thick spore coat. Spores are
      also more resistant to environmental stresses than yeast cells and display a
      spore-specific configuration of polysaccharides on their surfaces. Surprisingly,
      we found that the surface of the spore reacts with antibodies to the
      polysaccharide glucuronoxylomannan, the most abundant component of the
      polysaccharide capsule required for C. neoformans virulence. We explored the role
      of capsule polysaccharide in spore development by assessing spore formation in a
      series of acapsular strains and determined that capsule biosynthesis genes are
      required for proper sexual development and normal spore formation. Our findings
      suggest that C. neoformans spores may have an adapted cell surface that
      facilitates persistence in harsh environments and ultimately allows them to
      infect mammalian hosts.

PMID- 19181876
TI  - Use of self-controlled analytical techniques to assess the association between
      use of prescription medications and the risk of motor vehicle crashes.
AB  - Case-crossover and case-series analyses are 2 epidemiologic approaches that can
      be used to evaluate the association of exposures with acute events. Using a
      primary care database from the United Kingdom and these 2 statistical approaches,
      the authors investigated the impact of using benzodiazepines, nonbenzodiazepine
      hypnotics, beta-blockers, selective serotonin reuptake inhibitors, tricyclic
      antidepressants, opioids, and antihistamines on the risk of motor vehicle crashes
      in 1986-2004. For 49,821 individuals aged 18-74 years, involvement in a motor
      vehicle crash was documented. The outcome of the case-crossover analyses varied
      according to the choice of control period, so the case-series approach was
      preferred. The first 4 weeks of treatment with a combined acetaminophen and
      opioid preparation was associated with an increased risk of motor vehicle crash
      (incidence rate ratio = 2.06, 99% confidence interval: 1.84, 2.32), as was use of
      an opioid alone (incidence rate ratio = 1.70, 99% confidence interval: 1.39,
      2.08) and benzodiazepines (incidence rate ratio = 1.94, 99% confidence interval:
      1.62, 2.32). Use of selective serotonin reuptake inhibitors, nonbenzodiazepine
      hypnotics, and antihistamines for more than 4 weeks was associated with motor
      vehicle crash, but shorter term use was not. The results obtained are broadly
      consistent with those from well-designed case-control studies and demonstrate how
      case-only techniques optimize the use of routinely collected data for
      epidemiologic studies.

PMID- 19181877
TI  - Assistive technology, telecare and people with intellectual disabilities: ethical
      considerations.
AB  - Increasingly, commissioners and providers of services for people with
      intellectual disabilities are turning to assistive technology and telecare as a
      potential solution to the problem of the increased demand for services, brought
      about by an expanding population of people with intellectual disabilities in the
      context of relatively static or diminishing resources. While there are numerous
      potential benefits of assistive technology and telecare, both for service
      providers and service users, there are also a number of ethical issues. The aim
      of this paper is to raise these issues and to set them within the ethical
      framework proposed by Beauchamp and Childress. There is a need for a wider debate
      as a first step in the development of strategies to address the issues raised in
      the paper.

PMID- 19181878
TI  - Is once always enough? Revisiting the single use item.
AB  - The reuse of single use medical items is a complex ethical issue that many
      healthcare providers are faced with, for while recommendations and literature do
      not advocate the reuse of these items, the reality is that many single use items
      are frequently reused. Further, many healthcare workers are ethically divided
      over whether or not to share this information with their patients, or who should
      reveal this information. While single use items are convenient to use, the
      reality of the cost to the healthcare system and the environment is being
      realised. Three distinct issues in regard to reuse of single use items are
      explored: patient consent, fiscal responsibility and environmental stewardship.
      Exploring these issues through the ethical frameworks of utilitarianism,
      contractarianism, and land ethic or holism can offer guidance in attending to the
      question "is once always enough?" Applying an integrated ethical framework can
      further assist healthcare providers and stakeholders to make informed, ethical
      choices in regard to choosing single use medical devices and items. Short,
      fictionalised narratives based on authentic events are used to illustrate the
      ethical context of the reuse issue.

PMID- 19181875
TI  - The role of the ubiquitin proteasome system in ischemia and ischemic tolerance.
AB  - Ubiquitin modification targets a protein for rapid degradation by the proteasome.
      However, polyubiquitination of proteins can result in multiple functions
      depending on the topology of the ubiquitin chain. Therefore, ubiquitin signaling
      offers a more complex and versatile biology compared with many other
      posttranslational modifications. One area of potential for the application of
      this knowledge is the field of ischemia-induced brain damage, as occurs following
      a stroke. The ubiquitin proteasome system may exert a dual role on neuronal
      outcome following ischemia. Harmful ischemia results in an overload of the
      ubiquitin proteasome system, and blocking the proteasome reduces brain infarction
      following ischemia. However, the rapid and selective degradation of proteins
      following brief ischemia results in endogenous protection against ischemia.
      Therefore, further understanding of the molecular signaling mechanisms that
      regulate the ubiquitin proteasome system may reveal novel therapeutic targets to
      reduce brain damage when ischemia is predicted or reduce the activation of the
      cell death mechanisms and the inflammatory response following stroke. The aim of
      this review is to discuss some of the recent advances in the understanding of
      protein ubiquitination and its implications for novel stroke therapies.

PMID- 19181879
TI  - Myth of reincarnation: a challenge for mental health profession.
AB  - Mental health practitioners often come across a number of challenges in their
      clinical practice. One such challenge that posed a management dilemma presented
      with the history of reincarnation. This subject has been discussed in non
      scientific literature at length but there is an absolute paucity in scientific
      literature. This paper describes a case where a boy presented with memories of
      previous life that started haunting him and caused significant anxiety. The
      subject of reincarnation needs extensive research in order to understand and
      manage the resultant clinical challenges.

PMID- 19181880
TI  - Holding personal information in a disease-specific register: the perspectives of
      people with multiple sclerosis and professionals on consent and access.
AB  - OBJECTIVE: To determine the views of people with multiple sclerosis (MS) and
      professionals in relation to confidentiality, consent and access to data within a
      proposed MS register in the UK. DESIGN: Qualitative study using focus groups (10)
      and interviews (13). SETTING: England and Northern Ireland. PARTICIPANTS: 68
      people with MS, neurologists, MS nurses, health services management
      professionals, researchers, representatives from pharmaceutical companies and
      social care professionals. RESULTS: People with MS expressed open and altruistic
      views towards the use of their personal information to facilitate service
      provision and research, placing trust in responsible guardianship and legitimate
      use of their information. Participant's proposed that people with MS should be
      able to select their individual level of involvement in a register using levels
      of consent. It was agreed that access to the register should be governed by a
      guardianship committee composed of a range of stakeholders. People with MS did
      not wish their details to be used by marketing agencies and did not consider this
      a legitimate use of their data. Whilst participants were positive of the role a
      register could play in promoting research, participants felt that access to data
      by pharmaceutical industries should be administered by the guardianship
      committee. People with MS are concerned should their employers be able to access
      their personal information. Professionals were more cautious than people with MS
      in their approach to the use of patient personal data within a register.
      CONCLUSIONS: Whilst all stakeholders were positive of the benefits of an MS
      register, development of such a resource must incorporate robust data security
      and guardianship measures in order to ensure that, whilst opportunities are
      maximised, risks to the privacy of individuals and legal challenges to
      professionals are avoided.

PMID- 19181881
TI  - Prescribing placebos ethically: the appeal of negatively informed consent.
AB  - Kihlbom has recently argued that a system of seeking negatively informed consent
      might be preferable in some cases to the ubiquitous informed consent model.
      Although this theory is perhaps not powerful enough to supplant informed consent
      in most settings, it lends strength to Evans' and Hungin's proposal that it can
      be ethical to prescribe placebos rather than "active" drugs. This paper presents
      an argument for using negatively informed consent for the specific purpose of
      authorising the use of placebos in clinical contexts.

PMID- 19181882
TI  - The role of advance euthanasia directives as an aid to communication and shared
      decision-making in dementia.
AB  - Recent evaluation of the practice of euthanasia and related medical decisions at
      the end of life in the Netherlands has shown a slight decrease in the frequency
      of physician-assisted death since the enactment of the Euthanasia Law in 2002.
      This paper focuses on the absence of euthanasia cases concerning patients with
      dementia and a written advance euthanasia directive, despite the fact that the
      only real innovation of the Euthanasia Law consisted precisely in allowing
      physicians to act upon such directives. The author discusses two principal
      reasons for this absence. One relates to the uncertainty about whether patients
      with advanced dementia truly experience the suffering they formerly feared. There
      is reason to assume that they don't, as a consequence of psychological adaptation
      and progressive unawareness (anosognosia). The second, more fundamental reason
      touches upon the ethical relevance of shared understanding and reciprocity. The
      author argues that, next to autonomy and mercifulness, "reciprocity" is a
      condition sine qua non for euthanasia. The absence thereof in advanced dementia
      renders euthanasia morally inconceivable, even if there are signs of suffering
      and notwithstanding the presence of an advance euthanasia directive. This does
      not mean, however, that advance euthanasia directives of patients with dementia
      are worthless. They might very well have a role in the earlier stages of certain
      subtypes of the disease. To illustrate this point the author presents a case in
      which the advance directive helped to create a window of opportunity for
      reciprocity and shared decision-making.

PMID- 19181883
TI  - Does medicine still show an unresolved discrimination against women? Experience
      in two European university hospitals.
AB  - Have invisible barriers for women been broken in 2007, or do we still have to
      break through medicine's glass ceiling? Data from two of the most prestigious
      university hospitals in Barcelona with 700-800 beds, Hospital Clinic (HC) and
      Hospital de la Santa Creu i Sant Pau (HSCSP) address this issue. In the HSCSP,
      87% of the department chairs are men and 85% of the department unit chiefs are
      also men. With respect to women, only 5 (13%) are in the top position (department
      chair) and 4 (15%) are department unit chiefs. Similar statistics are also found
      at the HC: 87% of the department chairs and 89% of the department unit chiefs are
      men. Currently, only 6 women (13%) are in the top position and 6 (11%) are
      department unit chiefs. Analysis of the 2002 data of internal promotions in HC
      showed that for the first level (senior specialist) sex distribution was similar.
      Nevertheless, for the second level (consultant) only 25% were women, and for the
      top level (senior consultant) only 8% were women. These proportions have not
      changed in 2007 in spite of a 10% increase in leadership positions during this
      period. Similar proportions were found in HSCSP where 68% of the top promotions
      were held by men. The data obtained from these two different medical institutions
      in Barcelona are probably representative of other hospitals in Spain. It would be
      ethically desirable to have males and females in leadership positions in the
      medical profession.

PMID- 19181884
TI  - Seroxat and the suppression of clinical trial data: regulatory failure and the
      uses of legal ambiguity.
AB  - This article critically evaluates the Medicines and Healthcare products
      Regulatory Agency's announcement, in March 2008, that GlaxoSmithKline would not
      face prosecution for deliberately withholding trial data, which revealed not only
      that Seroxat was ineffective at treating childhood depression but also that it
      increased the risk of suicidal behaviour in this patient group. The decision not
      to prosecute followed a four and a half year investigation and was taken on the
      grounds that the law at the relevant time was insufficiently clear. This article
      assesses the existence of significant gaps in the duty of candour which had been
      assumed to exist between drugs companies and the regulator, and reflects upon
      what this episode tells us about the robustness, or otherwise, of the UK's
      regulation of medicines.

PMID- 19181885
TI  - Healthcare professionals' and researchers' understanding of cancer genetics
      activities: a qualitative interview study.
AB  - AIMS: To describe individuals' perceptions of the activities that take place
      within the cancer genetics clinic, the relationships between these activities and
      how these relationships are sustained. DESIGN: Qualitative interview study.
      PARTICIPANTS: Forty individuals involved in carrying out cancer genetics research
      in either a clinical (n = 28) or research-only (n = 12) capacity in the UK.
      FINDINGS: Interviewees perceive research and clinical practice in the
      subspecialty of cancer genetics as interdependent. The boundary between research
      and clinical practice is described as vague or blurred, and this ambiguity is
      regarded as being sustained by a range of methodological, ethical and economic
      factors. The implications of these findings for the "therapeutic misconception"
      are explored. It is argued that while research participation is seen as having
      therapeutic benefit for individual patients, the interviewees are not labouring
      under any misconceptions about the relationship between research and clinical
      care. It is suggested that concepts such as the "therapeutic misconception" may
      have less relevance in highly technological specialities that are characterised
      by a developing evidence base.

PMID- 19181886
TI  - Ethical and legal considerations in video recording neonatal resuscitations.
AB  - As guidelines for neonatal resuscitation evolve from a growing evidence base,
      clinicians must ensure that practice is closely aligned with the available
      evidence, based on methodologically sound and ethically conducted research. This
      paper reviews ethical, legal and risk-management issues arising during the design
      of a quality-assurance project to make video recordings of neonatal
      resuscitations after high-risk deliveries. The issues, which affect patients,
      researchers, staff and the hospital at large, include the following: 1) Informed
      consent for research involving emergency procedures is often not possible, for
      lack of time to provide sufficient information. The mental capacity of the
      subject or parent may be compromised by the impending emergency, and freedom of
      choice is threatened by the time pressure to consent. 2) Video recording of the
      inevitable medical errors raises issues of whether participating staff may be
      identifiable and accountable, affecting their willingness to participate in such
      research. The approach to staff participation and identification is reviewed. 3)
      The use of video data for education threatens the privacy of research subjects.
      The ethics of maintaining privacy is balanced with the ethics of using the data
      to improve practice of resuscitation. 4) The research subjects (patients, or the
      staff whose performance is being monitored) must be defined. 5) There are legal
      and ethical aspects of management and ownership of data. 6) The role of the Human
      Research Ethics Committee in protecting the research subject and possibly the
      medicolegal interests of the hospital is discussed. This paper reviews the
      literature and discusses the issues.

PMID- 19181887
TI  - Broadening consent--and diluting ethics?
AB  - Biobank research is potentially fruitful. It is argued that broad consent is
      acceptable for future research on biological material because a) the benefit is
      high, b) it pays respect to people's autonomy, c) it is consistent with current
      practices and d) because the risk is low. Furthermore, broad consent should be
      allowed if information is handled safely, people can withdraw and expanded
      research should be approved by an ethics review board. However, these arguments
      are flawed and the criteria for broad consent are either too restrictive to allow
      any research or fail to address important challenges with biobank research. Broad
      consent for biobank research can hide substantial ethical challenges and threaten
      trust in research. This does not mean that biobank research should be abandoned
      or that people cannot authorise future research on donated biological material.

PMID- 19181888
TI  - Do research ethics committees identify process errors in applications for ethical
      approval?
AB  - We analysed research ethics committee (REC) letters. We found that RECs
      frequently identify process errors in applications from researchers that are not
      deemed "favourable" at first review. Errors include procedural violations
      (identified in 74% of all applications), missing information (68%), slip-ups
      (44%) and discrepancies (25%). Important questions arise about why the level of
      error identified by RECs is so high, and about how errors of different types
      should be handled.

PMID- 19181889
TI  - Review of policies for injuries to research participants in India.
AB  - BACKGROUND: As there is little Indian data about severity, frequency and types of
      research related injuries, costs involved and policies regarding compensation,
      this study was conducted to review the present Indian scenario. METHODS: The
      study was carried out in three parts; a questionnaire-based survey, in-depth
      interviews, and a review of informed consent and insurance documents of projects
      submitted to three ethics committees. RESULTS: 47% of investigators were either
      unaware of, or had not understood, the legal requirements and depended on
      sponsors to manage these issues, whereas 74% of ethics committee members were
      aware of the requirements. Although 40% of investigators, 30% of ethics committee
      members and all sponsors had policies to manage compensation issues, these were
      mainly to provide immediate free medical care or reimbursement of expenses
      incurred for the acute management of an adverse event. Compensation for loss of
      time/wages, death, physical disability or long term incapacitation was not
      included. A review of informed consent and insurance documents showed that
      compensation issues were inadequately discussed, with only insurance certificates
      submitted to ethics committees. CONCLUSION: In India, there are no uniform
      policies and investigators are largely unaware of their responsibilities.
      Therefore, there is an urgent need to draft national guidelines regarding
      compensation for research injuries of research participants and highlight the
      responsibilities of each stakeholder. Potential research injuries should be
      categorised based on risk assessment, severity and seriousness of the injury.
      Further, it would be necessary to have arbitration committees to determine the
      extent of compensation. Training and awareness workshops for those involved in
      clinical research, including research participants, is also needed.

PMID- 19181890
TI  - Ethical aspects of research into Alzheimer disease. A European Delphi Study
      focused on genetic and non-genetic research.
AB  - BACKGROUND: Although genetic research into Alzheimer disease (AD) is increasing,
      the ethical aspects of this kind of research and the differences between ethical
      issues related to genetic and non-genetic research into AD have not yet received
      much attention. OBJECTIVES: (1) To identify and compare the five ethical issues
      considered most important by surveyed expert panellists in non-genetic and
      genetic AD research and (2) to compare our empirical findings with ethical issues
      in genetic research in general as described in the literature. METHOD: A modified
      Delphi study in two rounds RESULTS: Genetic and non-genetic research into AD
      generated an approximately equal number of topics with a considerable overlap.
      Different priorities in the ethics of both types of research were found. Genetic
      research raised new topics such as "confidentiality of genetic information" and
      "implications of research for relatives" which changes the impact and application
      of existing ethical topics such as "informed consent" and is judged to have more
      impact on both individuals and society. A difference with the results of more
      theoretical approaches on ethical aspects related to AD research was also found.
      CONCLUSIONS: Different priorities are given to ethical issues in genetic and non
      genetic research. These arise partly because genetic research causes unique and
      new questions, mostly related to the position of family members and the status of
      and access to genetic information. Differences found between the results of our
      empirical study and the more theoretical literature, suggest an additional value
      for empirical research in medical ethics.

PMID- 19181891
TI  - Theoretical and practical issues in the definition of health: insights from
      Aboriginal Australia.
AB  - This paper discusses attempts to define health within a public policy arena and
      practical and conceptual difficulties that arise. An Australian Aboriginal
      definition of health is examined. Although there are certain difficulties of
      translation, this definition is prominent in current Australian health policy and
      discourse about health. The definition can be seen as broadly holistic in
      comparison to other holistic definitions such as that of the World Health
      Organization. The nature of this holism and its grounding within the context of
      Aboriginal Australia is discussed. In particular, its implications for the
      phenomenon of medicalization, which may be associated with a holistic notion of
      health, is critically explored, as is the link of notions of health to culture
      and the question of the possibility of a universal definition of health. The
      question of to what extent a definition of health is inspirational or operational
      is also raised.

PMID- 19181892
TI  - The role of the arthropod stomatogastric nervous system in moulting behaviour and
      ecdysis.
AB  - A possible role of the insect stomatogastric nervous system (STNS) in ecdysis was
      first implied in early studies reporting on internal air pressure build-up in the
      digestive tract and air swallowing during ecdysis. The frontal ganglion, a major
      component of the insect STNS, was suggested to play an important part in this
      behaviour. Recent neurophysiological studies have confirmed the critical role of
      the STNS in the successful completion of both larval and adult moults in insects.
      In aquatic arthropods, though much less studied, the STNS plays an equally
      important and probably very similar role in water swallowing. Water uptake is
      instrumental in splitting the crustacean cuticle and allowing successful ecdysis.
      Current data are presented in a comparative view that contributes to our
      understanding of the role of the STNS in arthropod behaviour. It also sheds light
      on the question of homology of the STNS among the different arthropod groups. New
      insights into the neurohormonal control of ecdysis, related to the STNS in both
      insects and crustaceans, are also presented and comparatively discussed.

PMID- 19181893
TI  - Evidence for cranial endothermy in the opah (Lampris guttatus).
AB  - Cranial endothermy evolved independently in lamnid sharks, billfishes and tunas,
      and is thought to minimize the effects of ambient temperature change on both
      vision and neural function during deep dives. The opah, Lampris guttatus, is a
      large epipelagic-mesopelagic predator that makes repeated dives into cool waters
      to forage. To determine if L. guttatus exhibits cranial endothermy, we measured
      cranial temperatures in live, decked fish and identified potential sources of
      heat and mechanisms to conserve heat. In 40 opah (95.1+/-7.6 cm fork length), the
      temperature of the tissue behind the eye was elevated by a mean (+/-s.e.m.) of
      2.1+/-0.3 degrees C and a maximum of 6.3 degrees C above myotomal muscle
      temperature (T(m)), used as a proxy for ambient temperature. Cranial temperature
      varied significantly with T(m) and temperature elevation was greater at lower
      T(m). The proximal region of the paired lateral rectus extraocular muscle appears
      to be the primary source of heat. This muscle is the largest extraocular muscle,
      is adjacent to the optic nerve and brain and is separated from the brain only by
      a thin layer of bone. The proximal lateral rectus muscle is darker red in color
      and has a higher citrate synthase activity, indicating a higher capacity for
      aerobic heat production, than all other extraocular muscles. Furthermore, this
      muscle has a layer of fat insulating it from the gill cavity and is perfused by a
      network of arteries and veins that forms a putative counter-current heat
      exchanger. Taken together, these results support the hypothesis that the opah can
      maintain elevated cranial temperatures.

PMID- 19181894
TI  - Estimating energy expenditure of animals using the accelerometry technique:
      activity, inactivity and comparison with the heart-rate technique.
AB  - Several methods have been used to estimate the energy expenditure of free-ranging
      animals. A relatively new technique uses measures of dynamic body acceleration as
      a calibrated proxy for energy expenditure and has proved an excellent predictor
      of energy expenditure in active animals. However, some animals can spend much of
      their time inactive and still expend energy at varying rates for a range of
      physiological processes. We tested the utility of dynamic body acceleration to
      estimate energy expenditure during a range of active (locomotion, eating) and
      inactive (digesting, thermoregulating) behaviours exhibited by domestic chickens.
      We also compared this technique with the more established heart-rate method for
      estimating energy expenditure. During activity, the error of estimation using
      body acceleration was very similar to that from the heart-rate method.
      Importantly, our results also showed that body acceleration can be used to
      estimate energy expenditure when birds are inactive. While the errors surrounding
      these estimates were greater than those during activity, and those made using the
      heart-rate method, they were less than those made using interspecific allometric
      equations. We highlight the importance of selecting a methodology that is
      appropriate for the life-history of the subject animal. We suggest that, to
      achieve the greatest possible accuracy and precision when estimating energy
      expenditure in free-ranging animals, the two techniques should be combined, and
      both heart rate (f(H)) and dynamic body acceleration could be included as
      covariates in predictive models. Alternatively, measures of acceleration can be
      used to ascertain which behaviour is being exhibited at each moment and hence
      which predictive model should be applied.

PMID- 19181895
TI  - Physiological variation in amethyst sunbirds (Chalcomitra amethystina) over an
      altitudinal gradient in winter.
AB  - Flexibility of metabolic rates within a species allows for the colonization of
      different habitats along an altitudinal and thus temperature gradient. The
      distribution range of amethyst sunbirds (Chalcomitra amethystina) within southern
      Africa includes an altitudinal gradient from the Drakensberg to the coast of
      KwaZulu-Natal. We expected that over this altitudinal gradient amethyst sunbirds
      would exhibit variation in winter metabolic rates, particularly basal metabolic
      rates (BMR) and resting metabolic rate (RMR) pre- and post-acclimation. Sunbirds
      from three locations, Underberg (1553 m above sea level; asl), Howick (1075 m
      asl) and Oribi Gorge (541 m asl) were used for this study. Upon capture,
      metabolic rate was measured indirectly by quantifying oxygen consumption
      (V(O(2))) using flow-through respirometry, at 5 and 25 degrees C. Birds were then
      acclimated at 25 degrees C for 6 weeks on a 12 h:12 h L:D cycle. V(O(2)) was
      measured post-acclimation at eight different temperatures (15, 5, 10, 20, 30, 28,
      25 and 33 degrees C). We found little variation in winter V(O(2)) between
      individuals from the same locality, whereas significant variation was observed in
      V(O(2)) at the same temperatures between individuals from the different
      localities and thus between altitudes. In particular, winter BMR decreased
      significantly with decreasing altitude post-acclimation. This study emphasizes
      the need to understand plasticity/flexibility in metabolic rates and to
      acknowledge altitudinal differences within a species, to make accurate
      predictions about the thermal physiology of a species and its responses to
      changes in ambient temperatures.

PMID- 19181896
TI  - Increase in presenilin 1 (PS1) levels in senescence-accelerated mice (SAMP8) may
      indirectly impair memory by affecting amyloid precursor protein (APP) processing.
AB  - Senescence-accelerated mice (SAMP8) serve as a model for Alzheimer's disease (AD)
      as they exhibit early loss of memory and increased amyloid precursor protein
      (APP) expression. APP is a ubiquitous membrane protein that is physiologically
      processed by site-specific proteolysis firstly by alpha- or beta-secretases,
      releasing a large fragment called APP(S) that contains most of the extracellular
      sequences of APP, a small extracellular stub, the transmembrane region and the
      cytoplasmic tail of APP (;AICD'-APP intracellular domain). These are subsequently
      cleaved by gamma-secretase at multiple sites in the transmembrane region,
      releasing small peptides, Abeta(1-40) and Abeta(1-42), the major components of AD
      associated amyloid fibrils. gamma-secretase is a high-molecular-mass complex
      composed of presenilin-1 (PS1), nicastrin, APH-1 and Pen-2. As PS1 has been shown
      to play a critical role in facilitating gamma-secretase activity, and mutations
      in this protein are associated with familial AD (FAD), we have cloned it from
      SAMP8 mouse hippocampus and compared its sequence with those of other species.
      Furthermore, changes in the expression of PS1 with age in the hippocampal tissue
      of SAMP8 were studied. The results showed that the SAMP8 PS1 cDNA sequence is
      identical to that of normal mice. However, its expression in the hippocampus of
      SAMP8 exhibited an increase, while CD-1 mice, a strain that does not exhibit
      premature memory loss, showed no change with age. An increased amount or
      mutation(s) in PS1, which alters the stoichiometric balance of the gamma
      secretase complex, may be the cause of aberrant or increased processing of APP,
      resulting in Abeta accumulation leading to loss of memory.

PMID- 19181897
TI  - Priority rules govern the organization of traffic on foraging trails under
      crowding conditions in the leaf-cutting ant Atta colombica.
AB  - Foraging in leaf-cutting ants is generally organized along well-defined
      recruitment trails supporting a bi-directional flow of outbound and nestbound
      individuals. This study attempts to reveal the priority rules governing the
      organization of traffic on these trails. Ants were forced to move on a narrow
      trail, allowing the passage of only two individuals at a time. In this condition,
      a desynchronization of inbound and outbound traffic was observed, involving the
      formation of alternating clusters of inbound and outbound ants. Most clusters of
      inbound ants were headed by laden ants followed by unladen ants. This occurred
      because inbound unladen ants did not attempt to overtake the laden ants in front
      of them. As unladen ants move on average faster than laden ants, these ants were
      thus forced to decrease their speed. By contrast, this decrease was
      counterbalanced by the fact that, by staying in a cluster instead of moving in
      isolation, inbound unladen ants limit the number of head-on encounters with
      outbound ants. Our analysis shows that the delay induced by these head-on
      encounters would actually be twice as high as the delay induced by the forced
      decrease in speed incurred by ants staying in a cluster. The cluster organization
      also promotes information transfer about the level of food availability by
      increasing the number of contacts between outbound and inbound laden ants, which
      could possibly stimulate these former to cut and retrieve leaf fragments when
      reaching the end of the trail.

PMID- 19181898
TI  - Innate or learned acoustic recognition of avian predators in rodents?
AB  - Calls of avian predators potentially predict danger for murine rodents. Indeed,
      exposure of field-experienced rodents to owl calls induces defensive behavior
      suggesting that recognition of vocalizations of avian predators is innate. To
      address this hypothesis, we investigated whether laboratory-reared and predator
      naive rodents (mice, gerbils, rats) express defensive behavior in response to
      calls of different avian predators but we observed no such defensive behavior. We
      then asked whether the calls of avian predators are faster or better learned as a
      danger-predicting cue than the calls of avian non-predators. All calls could be
      learned as danger-predicting cues, but we found no differences in the speed or
      strength of the learning. Taken together, our results suggest that there is no
      innate recognition of the calls of avian predators in murine rodents and that the
      recognition of the calls of avian predators observed in field-experienced rodents
      is acquired by learning.

PMID- 19181899
TI  - Do mitochondrial properties explain intraspecific variation in thermal tolerance?
AB  - As global temperatures rise, there is a growing need to understand the
      physiological mechanisms that determine an organism's thermal niche. Here, we
      test the hypothesis that increases in mitochondrial capacity with cold
      acclimation and adaptation are associated with decreases in thermal tolerance
      using two subspecies of killifish (Fundulus heteroclitus) that differ in thermal
      niche. We assessed whole-organism metabolic rate, mitochondrial amount and
      mitochondrial function in killifish acclimated to several temperatures.
      Mitochondrial enzyme activities and mRNA levels were greater in fish from the
      northern subspecies, particularly in cold-acclimated fish, suggesting that the
      putatively cold-adapted northern subspecies has a greater capacity for increases
      in mitochondrial amount in response to cold acclimation. When tested at the
      fish's acclimation temperature, maximum ADP-stimulated (State III) rates of
      mitochondrial oxygen consumption in vitro were greater in cold-acclimated
      northern fish than in southern fish but did not differ between subspecies at
      higher acclimation temperatures. Whole-organism metabolic rate was greater in
      fish of the northern subspecies at all acclimation temperatures. Cold acclimation
      also changed the response of mitochondrial respiration to acute temperature
      challenge. Mitochondrial oxygen consumption was greater in cold-acclimated
      northern fish than in southern fish at low test temperatures, but the opposite
      was true at high test temperatures. These differences were reflected in whole
      organism oxygen consumption. Our data indicate that the plasticity of
      mitochondrial function and amount differs between killifish subspecies, with the
      less high-temperature tolerant, and putatively cold adapted, northern subspecies
      having greater ability to increase mitochondrial capacity in the cold. However,
      there were few differences in mitochondrial properties between subspecies at warm
      acclimation temperatures, despite differences in both whole-organism oxygen
      consumption and thermal tolerance at these temperatures.

PMID- 19181900
TI  - Control and function of arm swing in human walking and running.
AB  - We investigated the control and function of arm swing in human walking and
      running to test the hypothesis that the arms act as passive mass dampers powered
      by movement of the lower body, rather than being actively driven by the shoulder
      muscles. We measured locomotor cost, deltoid muscle activity and kinematics in 10
      healthy adult subjects while walking and running on a treadmill in three
      experimental conditions: control; no arms (arms folded across the chest); and arm
      weights (weights worn at the elbow). Decreasing and increasing the moment of
      inertia of the upper body in no arms and arm weights conditions, respectively,
      had corresponding effects on head yaw and on the phase differences between
      shoulder and pelvis rotation, consistent with the view of arms as mass dampers.
      Angular acceleration of the shoulders and arm increased with torsion of the trunk
      and shoulder, respectively, but angular acceleration of the shoulders was not
      inversely related to angular acceleration of the pelvis or arm. Restricting arm
      swing in no arms trials had no effect on locomotor cost. Anterior and posterior
      portions of the deltoid contracted simultaneously rather than firing alternately
      to drive the arm. These results support a passive arm swing hypothesis for upper
      body movement during human walking and running, in which the trunk and shoulders
      act primarily as elastic linkages between the pelvis, shoulder girdle and arms,
      the arms act as passive mass dampers which reduce torso and head rotation, and
      upper body movement is primarily powered by lower body movement.

PMID- 19181901
TI  - Interaction of visual and odour cues in the mushroom body of the hawkmoth Manduca
      sexta.
AB  - The responses to bimodal stimuli consisting of odour and colour were recorded
      using calcium-sensitive optical imaging in the mushroom bodies of the hawkmoth
      Manduca sexta. The results show that the activity in the mushroom bodies is
      influenced by both olfaction and vision. The interaction between the two
      modalities depends on the odour and the colour of the visual stimulus. A blue
      stimulus suppressed the response to a general flower scent (phenylacetaldehyde).
      By contrast, the response to a green leaf scent (1-octanol) was enhanced by the
      presence of the blue stimulus. A green colour had no influence on these odours
      but caused a marked increase in the response to an odour component (benzaldehyde)
      of the hawkmoth-pollinated Petunia axillaris.

PMID- 19181902
TI  - The specific binding sites of eyestalk- and pericardial organ-crustacean
      hyperglycaemic hormones (CHHs) in multiple tissues of the blue crab, Callinectes
      sapidus.
AB  - Crustacean hyperglycaemic hormone from the pericardial organ (PO-CHH) is a CHH
      related neuropeptide but its function and target tissues are not known in
      crustaceans. To investigate this issue, we employed radiolabelled ligand binding
      and cGMP assays, using eyestalk-CHH (ES-CHH) as a reference neuropeptide. The
      membranes were prepared from various tissues of Callinectes sapidus:
      hepatopancreas, hindgut, midgut, gills, heart, abdominal muscles and
      scaphognathites. Like ES-CHH, recombinant PO-CHH (rPO-CHH) specifically bound to
      the membranes of scaphognathites=abdominal muscles>midgut>gills> heart>hindgut
      and hepatopancreas (list order corresponds to the number of binding sites). The
      specific binding sites of (125)I-ES-CHH in hepatopancreas and gills were
      saturable and displaceable. The abdominal muscle membrane binding sites were
      specific and saturable to both CHHs. These binding sites were displaced by
      homologous neuropeptides, but poorly displaced by the heterologous counterpart.
      As for the second messenger, the expected increment (3- to >20-fold) in the
      amount of cGMP produced by ES-CHH was noted in most tissues tested except midgut.
      Recombinant PO-CHH increased cGMP production 1.5- to 4-fold in scaphognathites,
      heart, midgut, hindgut and abdominal muscles. The results obtained from the
      binding study suggest that PO-CHH also has multiple target tissues of which
      abdominal muscles and scaphognathites are the primary ones. The differences in
      the primary amino acid sequences of PO-CHH and ES-CHH, particularly in the C
      terminal region and in the amidation at C-terminus, may contribute to the
      truncated responses of hyperglycaemia, cGMP stimulation and binding affinity.

PMID- 19181904
TI  - Frequency information in the vibration-cued escape hatching of red-eyed
      treefrogs.
AB  - Incidental acoustic and vibrational cues generated by predators are a potential
      source of information for prey assessing risk. Substrate vibrations should be
      excited by most predators, and frequency, amplitude or temporal properties could
      allow prey to distinguish predator from benign-source vibrations. Red-eyed
      treefrog embryos detect egg predators using vibrations excited during attacks,
      hatching rapidly and prematurely to escape. We recorded vibrations in egg
      clutches during attacks by five species of predators and three common types of
      benign physical disturbance. We analyzed their frequency distributions to assess
      if and how frequency properties could be used to discriminate between vibration
      sources and used vibration playbacks to examine the effects of frequency
      properties on the escape hatching response. Vibrations produced by predators and
      benign disturbances generally have broad and overlapping frequency distributions,
      and all frequencies excited by attacks are also excited by benign disturbances.
      Decision rules based on the frequency distribution of vibrations alone would
      therefore result in either high levels of hatching in response to benign
      vibrations (false alarms) or common failures to hatch in response to predators
      (missed cues). Nevertheless, embryos hatch in response to predator and not benign
      disturbances in nature, and our playback results show that vibration frequency
      information is an important component of their hatching decision. Embryos combine
      frequency with temporal information to refine their hatching response. Moreover,
      comparing frequency spectra of predator and benign vibrations suggests that the
      presence of energy in frequencies outside the range characteristic of attacks
      might serve as an indicator of benign disturbance.

PMID- 19181905
TI  - Numerical investigation of the hydrodynamics of anguilliform swimming in the
      transitional and inertial flow regimes.
AB  - We employ numerical simulation to investigate the hydrodynamic performance of
      anguilliform locomotion and compare it with that of carangiform swimming as the
      Reynolds number (Re) and the tail-beat frequency (Strouhal number, St) are
      systematically varied. The virtual swimmer is a 3-D lamprey-like flexible body
      undulating with prescribed experimental kinematics of anguilliform type.
      Simulations are carried out for three Reynolds numbers spanning the transitional
      and inertial flow regimes, Re=300, 4000 (viscous flow), and infinity (inviscid
      flow). The net mean force is found to be mainly dependent on the tail-beat
      frequency rather than the tail-beat amplitude. The critical Strouhal number, St,
      at which the net mean force becomes zero (constant-speed self-propulsion) is,
      similar to carangiform swimming, a decreasing function of Re and approaches the
      range of St numbers at which most anguilliform swimmers swim in nature (St
      approximately 0.45) only as Re increases. The anguilliform swimmer's force time
      series is characterized by significantly smaller fluctuations above the mean than
      that for carangiform swimmers. In stark contrast with carangiform swimmers, the
      propulsive efficiency of anguilliform swimmers at St is not an increasing
      function of Re but instead is maximized in the transitional regime. Furthermore,
      the power required for anguilliform swimming is less than that for the
      carangiform swimmer at the same Re. We also show that the form drag decreases
      while viscous drag increases as St increases. Finally, our simulations reinforce
      our previous finding for carangiform swimmers that the 3-D wake structure depends
      primarily on the Strouhal number.

PMID- 19181903
TI  - Exploring the mechanical basis for acceleration: pelvic limb locomotor function
      during accelerations in racing greyhounds (Canis familiaris).
AB  - Animals in their natural environments are confronted with a regular need to
      perform rapid accelerations (for example when escaping from predators or chasing
      prey). Such acceleration requires net positive mechanical work to be performed on
      the centre of mass by skeletal muscle. Here we determined how pelvic limb joints
      contribute to the mechanical work and power that are required for acceleration in
      galloping quadrupeds. In addition, we considered what, if any, biomechanical
      strategies exist to enable effective acceleration to be achieved. Simultaneous
      kinematic and kinetic data were collected for racing greyhounds undergoing a
      range of low to high accelerations. From these data, joint moments and joint
      powers were calculated for individual hindlimb joints. In addition, the mean
      effective mechanical advantage (EMA) of the limb and the ;gear ratio' of each
      joint throughout stance were calculated. Greatest increases in joint work and
      power with acceleration appeared at the hip and hock joints, particularly in the
      lead limb. Largest increases in absolute positive joint work occurred at the hip,
      consistent with the hypothesis that quadrupeds power locomotion by torque about
      the hip. In addition, hindlimb EMA decreased substantially with increased
      acceleration - a potential strategy to increase stance time and thus ground
      impulses for a given peak force. This mechanism may also increase the mechanical
      advantage for applying the horizontal forces necessary for acceleration.

PMID- 19181906
TI  - Investigation of somatic NKX2-5 mutations in congenital heart disease.
AB  - BACKGROUND: Reports of somatic mutations found in hearts with cardiac septal
      defects have suggested that these mutations are aetiologic in pathologic cardiac
      development. However, the hearts in these reports had been fixed in formalin for
      over 22 years. Because of the profound implication of this finding, we attempted
      to replicate it using fresh frozen tissue obtained in the current era from 28
      patients with septal defects who underwent cardiac surgery and who were enrolled
      in our congenital heart disease tissue bank. METHODS: Our cohort included
      patients with atrial septal defects (ASD, n = 13), ventricular septal defects
      (VSD, n = 5), and atrioventricular canal defects (AVCD, n = 10). Cardiac tissue
      samples were collected both from diseased tissue located immediately adjacent to
      the defect and from anatomically normal tissue located at a site remote from the
      defect (right atrial appendage). Tissue samples were immediately frozen in liquid
      nitrogen and stored at -80 degrees C. Genomic DNA was isolated and amplified
      using the same methodology described in the previously published reports. 42
      pathologic cardiac tissue samples were sequenced. RESULTS: One non-synonymous
      germline sequence variant was identified in one patient. Two synonymous germline
      sequence variants were identified in two separate patients. A common single
      nucleotide polymorphism (SNP) was identified in 16 patients. Based on the
      incidence of somatic mutations described in the previously published reports, our
      study was adequately powered to replicate the previous studies. No evidence of
      somatic mutations was found in this study. CONCLUSION: Somatic mutations in NKX2
      5 do not represent an important aetiologic pathway in pathologic cardiac
      development in patients with cardiac septal defects.

PMID- 19181907
TI  - Genomic rearrangements in OPA1 are frequent in patients with autosomal dominant
      optic atrophy.
AB  - INTRODUCTION: Autosomal dominant optic atrophy (ADOA) is considered as the most
      common form of hereditary optic neuropathy. Although genetic linkage studies
      point to the OPA1 locus on chromosome 3q28-q29 as by far the most common gene
      locus, previous screening studies-based on sequencing of the coding exons
      detected OPA1 mutations in only 32-70% of ADOA patients. We therefore
      hypothesised that larger deletions or duplications that remained undetected in
      previous screening approaches may substantially contribute to the prevalence of
      OPA1 mutations in ADOA. METHODS: 42 independent ADOA patients were analysed for
      the presence of genomic rearrangements in OPA1 by means of multiplex ligation
      probe amplification (MLPA). Deletions or duplications were confirmed either by
      long distance polymerase chain reaction (PCR) and breakpoint sequencing or loss
      of heterozygosity analyses with flanking microsatellite markers. Patients
      underwent ophthalmological examination including visual acuity, colour vision
      testings, perimetry and funduscopy. RESULTS: We identified genomic rearrangements
      in 8 of 42 patients, including single exon deletions of exon 9 and exon 24,
      respectively, a deletion of exons 1-5, two different deletions of the complete
      OPA1 gene as well as a duplication of the exons 7-9, with the latter being
      present in three unrelated families. Patients' phenotypes were highly variable,
      similar to patients with point mutation in OPA1. DISCUSSION: Our findings show
      that gross genomic aberrations at the OPA1 gene locus are frequent in ADOA and
      substantially contribute to the spectrum and prevalence of OPA1 mutations in ADOA
      patients. They further strengthen the hypothesis that haploinsufficiency is a
      major pathomechanism in OPA1 associated ADOA.

PMID- 19181908
TI  - Health behavior interests of adolescents with unhealthy diet and exercise:
      implications for weight management.
AB  - This study sought to determine individual factors that may influence adolescents'
      interests in various health behaviors and, by extension, their potential interest
      in programs that promote healthy lifestyles and reduce obesity. The sample
      consisted of 737 rural Pennsylvania (United States) middle and high school
      students not involved in either healthy exercise or dietary behaviors (a target
      group for health-promoting interventions). Participants completed a self-report
      measure of their general health functioning, including their interests in sports
      programs, outdoor recreation programs, weightlifting, weight loss and healthy
      eating/cooking. Nurses measured body mass indices (BMIs). The vast majority of
      the sample endorsed self-efficacy in healthy eating and physical activity, and
      this self-efficacy was associated with interest in a healthy diet and outdoor
      recreation. Interest in healthy activities was consistently higher among 7th
      graders (age mean = 12.6 years) than 11th graders (age mean = 16.3 years).
      Females were more interested in weight loss and healthy eating/cooking, whereas
      males were more interested in weightlifting. Higher BMI only predicted interest
      in weight loss. These results indicate that adolescent health interests vary on
      the basis of their gender, grade level, BMI and self-efficacy. These trends are
      potentially important to consider when seeking to match intervention programs to
      adolescent interests.

PMID- 19181909
TI  - Teaching massage to nursing students of geriatrics through active learning.
AB  - The use of massage in nursing practice has declined through the years in favor of
      high-tech interventions. This article describes a project using active learning
      to teach nursing students massage with dementia residents in assisted living.
      Students participated in a workshop to practice basic relaxation massage
      techniques with the guidance of their clinical instructor and then provided
      massages to resident volunteers. Afterward, students discussed their experience
      and completed a resident assessment form. The students requested more such
      activities, and the residents and facility management invited the students to
      return for another session. The instructor observed growth in the students'
      assessment skills and in their confidence. Use of massage to teach nursing
      students how to care for and relate to older adults with cognitive impairment is
      recommended. Further research is needed on the use of massage as an active
      learning method for nursing students in long-term care.

PMID- 19181910
TI  - Chicken or egg: physical activity in COPD revisited.

PMID- 19181911
TI  - Chronic thromboembolic pulmonary hypertension: a tribute to pulmonary
      endarterectomy.

PMID- 19181912
TI  - The genetic and cardiovascular aspects of obstructive sleep apnoea/hypopnoea
      syndrome.

PMID- 19181913
TI  - Serum adipocyte-fatty acid binding protein level is elevated in severe OSA and
      correlates with insulin resistance.
AB  - Obstructive sleep apnoea (OSA) is associated with insulin resistance and
      metabolic syndrome. There is evidence that adipocyte-fatty acid binding protein
      (A-FABP) may be involved in the development of cardiometabolic dysfunction. The
      present authors hypothesise that A-FABP is upregulated in OSA. A total of 124
      males without hypertension, diabetes mellitus, hyperlipidaemia or cardiovascular
      disease were recruited and underwent polysomnography. Serum A-FABP levels showed
      significant positive correlations with duration of oxygen desaturation and
      minimal oxygen saturation, fasting insulin and insulin resistance index by
      homeostasis model assessment. When subjects were divided into tertiles according
      to apnoea/hypopnoea index (AHI), serum A-FABP levels were significantly higher in
      the group with AHI >/=34.4 events.h(-1) than the groups with AHI 13.2-34.4
      events.h(-1) or with AHI <13.2 events.h(-1). Serum A-FABP levels were
      significantly higher in the AHI >/=34.4 group than obesity-matched subjects with
      AHI <34.4 events.h(-1). Serum adipocyte-fatty acid binding protein levels
      correlated with obstructive sleep apnoea and insulin resistance, independently of
      obesity, and were significantly higher in severe obstructive sleep apnoea.
      Adipocyte-fatty acid binding protein may play a role in obstructive sleep apnoea
      and metabolic dysfunction.

PMID- 19181914
TI  - Regulation of cytokine expression in human plasmacytoid dendritic cells by
      prostaglandin I2 analogues.
AB  - Plasmacytoid dendritic cells (pDCs) are critical in controlling adaptive
      immunity, but the mechanisms governing cytokine expression remain incompletely
      defined. Analogues of prostaglandin (PG)I(2), such as iloprost, can modulate
      functions of myeloid dendritic cells, but their involvement in the regulation of
      human pDCs remains unknown. To this end, the regulatory role of PGI(2) analogues
      on cytokine expression in pDCs was investigated. Circulating pDCs were
      magnetically sorted with BDCA-4 cell isolation kits from human peripheral blood
      mononuclear cells and treated with varying concentrations of iloprost with or
      without the addition of Toll-like receptor agonists, or an I prostanoid (IP)
      receptor antagonist, CAY10449. The levels of tumour necrosis factor (TNF)-alpha,
      interferon (IFN)-alpha and interleukin (IL)-10 were measured by ELISA. Iloprost
      induced IL-10 expression, but suppressed CpG oligodeoxynucleotide- (or imiquimod
      ) induced TNF-alpha and IFN-alpha production in pDCs. This effect was reversed by
      the addition of CAY10449. Forskolin, a cyclic adenosine monophosphate activator,
      conferred a similar modulating effect to that noted in iloprost-treated pDCs,
      although a higher concentration of forskolin was required to exert the same
      effect. Iloprost enhanced interleukin-10 and suppressed Toll-like receptor
      mediated tumour necrosis factor-alpha and interferon-alpha production of human
      plasmacytoid dendritic cells via the I prostanoid receptor and, in part, the
      cyclic adenosine monophosphate pathway.

PMID- 19181915
TI  - Some principles and practices of genetic biobanking studies.
AB  - Genetic biobanking studies are becoming increasingly common as researchers
      recognise the need for large samples to identify the genetic basis of
      susceptibility to complex disease. In the present review, the authors give a
      brief overview of some of the issues that should be considered when implementing
      such a large-scale project, from study design to sample management, data coding
      and storage to the statistical analysis and engagement with the public. Specific
      solutions to these issues are presented, as implemented in the Generation
      Scotland projects, but the general principles outlined are relevant to any
      biobanking study.

PMID- 19181916
TI  - Sublobar resection for lung cancer.
AB  - Sublobar resection for small lung cancers has been debated frequently and is
      still a controversial issue. The only randomised trial comparing lobectomy with
      sublobar resections found a significantly higher recurrence rate for the latter,
      but failed to show significant differences in survival, although survival was
      better for the lobectomy group. One meta-analysis and several nonrandomised
      comparisons have confirmed these results. In general, lobectomy and sublobar
      resections have similar 5-yr survival rates. Local recurrence after wedge
      resection is higher than after segmentectomy. However, for patients aged >71 yrs,
      lobectomy and wedge resection are associated with similar survival. For tumours
      of </=2 cm, segmentectomy is equivalent to lobectomy, but survival after
      segmentectomy is worse if performed for larger tumours. For both segmentectomy
      and wedge resection, tumour margins should be >/=1 cm wide to avoid recurrence.
      For pure bronchioloalveolar carcinoma of </=2 cm, diagnosed intraoperatively with
      certainty, sublobar resection seems equivalent to lobectomy, and because there is
      no nodal involvement, systematic nodal dissection may not be necessary. In case
      of doubt, however, lobectomy with systematic nodal dissection will ensure
      complete resection and adequate staging. More randomised trials are needed to
      confirm all these issues.

PMID- 19181917
TI  - EGFR-TKI and lung adenocarcinoma with CNS relapse: interest of molecular follow
      up.
AB  - The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)
      erlotinib improves survival of lung cancer as second- or third-line therapy.
      However, after an initial response, most patients will recur, particularly within
      the central nervous system. The present study reports the case of a 27-yr-old
      nonsmoking male presenting with a metastatic lung adenocarcinoma with EGFR exon
      19 deletion, associated with sensitivity to EGFR-TKI. Gefitinib, followed by
      chemotherapy and finally erlotinib resulted in prolonged disease control, until
      multiple liver metastases were detected. After stopping EGFR-TKI, brain
      metastases with carcinomatous meningitis were diagnosed. A secondary T790M
      mutation, associated with resistance to EGFR-TKI, was found on the liver biopsy
      but not in the cerebrospinal fluid. Erlotinib was reintroduced and allowed a
      quick neurological improvement, even though the extra-cranial disease remained
      resistant to erlotinib. The present report underscores the interest of molecular
      monitoring in lung cancer. Persistent cerebral tyrosine kinase inhibitor
      sensitivity should be considered in patients presenting with an early central
      nervous system relapse after stopping epidermal growth factor receptor tyrosine
      kinase inhibitor, even with a T790M-resistant mutation in noncerebral metastases.
      Questions remain concerning the selection of sub-clones during epidermal growth
      factor receptor tyrosine kinase inhibitor therapy, which could differ according
      to metastatic sites, especially in the central nervous system.

PMID- 19181918
TI  - A green oral appliance.

PMID- 19181919
TI  - VATS or simple talc poudrage under medical thoracoscopy for recurrent spontaneous
      pneumothorax.

PMID- 19181920
TI  - Methodological issues in therapeutic trials of COPD.

PMID- 19181921
TI  - Inhaled insulin does not trigger lung inflammation and airway remodelling.

PMID- 19181922
TI  - Palliative and end-of-life care for patients with severe COPD.

PMID- 19181923
TI  - No effects of EPHX1 polymorphisms on the level or change of FEV1 in the general
      population.

PMID- 19181924
TI  - Pulmonary hypertension therapy and COPD: still many questions to be answered.

PMID- 19181925
TI  - Pulmonary hypertension therapy and COPD: still many questions to be answered.

PMID- 19181926
TI  - Pulmonary hypertension therapy and COPD: still many questions to be answered.

PMID- 19181927
TI  - Regional variations in pulmonary endarterectomy rates within the UK.

PMID- 19181929
TI  - Serum DNase I, soluble Fas/FasL levels and cell surface Fas expression in
      patients with SLE: a possible explanation for the lack of efficacy of hrDNase I
      treatment.
AB  - The objectives of the study are to evaluate DNase I serum levels and their
      correlation with soluble Fas (sFas) and soluble Fas ligand (sFasL) and with cell
      surface Fas expression in patients with systemic lupus erythematosus (SLE), thus
      contributing to the dysregulated apoptosis typical of the disease. The methods
      include the following: Serum DNase I levels in patients and in controls were
      detected using the dot blot method and quantified by densitometry; sFas and sFasL
      were quantified using an ELISA system. Cell surface Fas expression was evaluated
      by FACS analysis. Apoptosis was studied by means of internucleosomal DNA
      degradation using a commercially available kit. The results are as follows: We
      found a significant difference in DNase I, sFas and sFasL serum levels between
      patients and controls. Levels of DNase I <7.79 ng ml(-1) are more represented in
      patients with SLE. Active SLE is strongly associated with high sFas levels and
      detectable sFasL. DNase I does not correlate with sFas or sFasL, whereas it
      correlates with T cell surface Fas expression that is higher in patients with
      active SLE than in healthy controls. Finally, administration of exogenous human
      recombinant DNase (hrDNase) I to freshly isolated T cells up-regulates cell
      surface Fas expression and induces increased susceptibility to Fas-mediated
      apoptosis. In conclusion, our findings confirm that DNase I is low in SLE and
      suggest that it may play a role in apoptosis in SLE by regulating the surface
      expression of the cell death molecule Fas. This role may contribute to explain
      the inefficacy of hrDNase I in SLE, a treatment proposed for the ability of DNase
      I to remove DNA from auto-antigenic nucleoprotein complexes.

PMID- 19181931
TI  - Differential regulation of splenic CD8- dendritic cells and marginal zone B cells
      by Notch ligands.
AB  - The importance of Notch signaling to maintain CD8- dendritic cells (DCs) in the
      spleen has recently been revealed. However, the ligand responsible for this Notch
      signaling has not been determined yet. In this study, we demonstrated that
      blocking of Delta-like (Dll) 1 alone had no significant effect on the maintenance
      of CD8- DCs while marginal zone (MZ) B cells were significantly reduced in the
      spleen of mice. On the other hand, blocking of Dll1, Dll4, Jagged1 and Jagged2
      significantly decreased CD8- DCs. All these Notch ligands are expressed
      predominantly in the red pulp of the spleen where CD8- DCs reside. These results
      indicate a differential regulation of CD8- DCs and MZ B cells by Notch ligands in
      the spleen.

PMID- 19181930
TI  - The transcription repressor, ZEB1, cooperates with CtBP2 and HDAC1 to suppress IL
      2 gene activation in T cells.
AB  - Activation of T cells leads to the induction of many cytokine genes that are
      required for appropriate immune responses, including IL-2, a key cytokine for T
      cell proliferation and homeostasis. The activating transcription factors such as
      nuclear factor of activated T cells, nuclear factor kappaB/Rel and activated
      protein-1 family members that regulate inducible IL-2 gene expression have been
      well documented. However, negative regulation of the IL-2 gene is less studied.
      Here we examine the role of zinc finger E-box-binding protein (ZEB) 1, a
      homeodomain/Zn finger transcription factor, as a repressor of IL-2 gene
      transcription. We show here that ZEB1 is expressed in non-stimulated and
      stimulated T cells and using chromatin immunoprecipitation assays we show that
      ZEB1 binds to the IL-2 promoter. Over-expression of ZEB1 can repress IL-2
      promoter activity, as well as endogenous IL-2 mRNA production in EL-4 T cells,
      and this repression is dependent on the ZEB-binding site at -100. ZEB1 cooperates
      with the co-repressor C-terminal-binding protein (CtBP) 2 and with histone
      deacetylase 1 to repress the IL-2 promoter and this cooperation depends on the
      ZEB-binding site in the promoter as well as the Pro-X-Asp-Leu-Ser protein-protein
      interaction domain in CtBP2. Thus, ZEB1 may function to recruit a repressor
      complex to the IL-2 promoter.

PMID- 19181932
TI  - Peptides with dual binding specificity for HLA-A2 and HLA-E are encoded by
      alternatively spliced isoforms of the antioxidant enzyme peroxiredoxin 5.
AB  - Peptides with dual binding specificity for classical HLA class I and non
      classical HLA-E molecules have been identified in virus-encoded proteins, but not
      in cellular proteins from normal or neoplastic cells. Expression screening of a
      melanoma cDNA library with a CTL clone recognizing an HLA-A2-restricted tumor
      specific epitope encoded by mutant peroxiredoxin 5 (Prdx5), a stress-inducible
      peroxidase, led to the identification of two alternatively spliced isoforms of
      the same gene. These isoforms, which lack the catalytic cysteine fundamental for
      enzymatic activity, showed widespread expression in neoplastic and normal tissues
      but were unstable at the protein level, being detectable, following transient
      transfection, only after lactacystin treatment to inhibit proteasomal
      degradation. Isoform-specific sequences which formed, respectively, as result of
      exon 1 splicing to either exon 3 or 4, encoded two distinct nonapeptides
      (AMAPIKTHL and AMAPIKVRL, not present in the full-length protein) with anchor
      residues for HLA-A2 and HLA-E molecules and able to stabilize HLA-A2 and HLA-E
      cell surface expression. HLA-E+ targets, loaded with these peptides, were not
      recognized by NK cells expressing CD94/NKG2A inhibitory or CD94/NKG2C activatory
      receptors. However, both peptides were recognized, although with low avidity, by
      HLA-E-restricted CD8+ CTL. The nonapeptide AMAPIKVRL was used to elicit HLA-A2
      restricted CTL clones that killed peptide-pulsed lymphoblastoid cell lines and
      melanoma cells expressing the corresponding Prdx5 isoform. Our results suggest
      that alternatively spliced isoforms of Prdx5, through the generation of HLA-E-
      and HLA-A2-restricted peptides may be part of immune-mediated stress response
      contributing to the detection and elimination of damaged normal or neoplastic
      cells.

PMID- 19181933
TI  - Regulation of ATP-sensitive K+ channels by caveolin-enriched microdomains in
      cardiac myocytes.
AB  - AIMS: ATP-sensitive potassium (K(ATP)) channels in the heart are critical
      regulators of cellular excitability and action potentials during ischaemia.
      However, little is known about subcellular localization of these channels and
      their regulation. The present study was designed to explore the potential role of
      caveolae in the regulation of K(ATP) channels in cardiac ventricular myocytes.
      METHODS AND RESULTS: Both adult and neonatal rat cardiomyocytes were used.
      Subcellular fractionation by density gradient centrifugation, western blotting,
      co-immunoprecipitation, and immunofluorescence confocal microscopy were employed
      in combination with whole-cell voltage clamp recordings and siRNA gene silencing.
      We detected that the majority of K(ATP) channels on the plasma membrane of
      cardiac myocytes were localized in caveolin-3-enriched microdomains by cell
      fractionation and ultracentrifugation followed by western blotting.
      Immunofluorescence confocal microscopy revealed extensive colocalization of
      K(ATP) channel pore-forming subunit Kir6.2 and caveolin-3 along the plasma
      membrane. Co-immunoprecipitation of cardiac myocytes showed significant
      association of Kir6.2, adenosine A(1) receptors, and caveolin-3. Furthermore,
      whole-cell voltage clamp studies suggested that adenosine A(1) receptor-mediated
      activation of K(ATP) channels was largely eliminated by disrupting caveolae with
      methyl-beta-cyclodextrin or by small interfering RNA, whereas pinacidil-induced
      K(ATP) activation was not altered. CONCLUSION: We demonstrate that K(ATP)
      channels are localized to caveolin-enriched microdomains. This microdomain
      association is essential for adenosine receptor-mediated regulation of K(ATP)
      channels in cardiac myocytes.

PMID- 19181934
TI  - IL-10 attenuates TNF-alpha-induced NF kappaB pathway activation and cardiomyocyte
      apoptosis.
AB  - AIMS: We have recently reported that tumour necrosis factor-alpha (TNF-alpha)
      increases oxidative stress and apoptosis in cardiomyocytes by upregulating p38
      mitogen-activated protein (MAP) kinase (MAPK) phosphorylation. Interleukin-10 (IL
      10) blocked these effects of TNF-alpha by upregulating extracellular signal
      regulated kinase 1/2 (ERK 1/2) MAPK phosphorylation. However, the precise site of
      this IL-10 action is still unknown, and this is investigated in the present
      study. METHODS AND RESULTS: Cardiomyocytes isolated from adult Sprague-Dawley
      rats were exposed to TNF-alpha (10 ng/mL), IL-10 (10 ng/mL), and IL-10+TNF-alpha
      (ratio 1) for 4 h. Hydrogen peroxide and antioxidant trolox were used as positive
      controls. Exposure to TNF-alpha resulted in an increase in the production of
      reactive oxygen species, the number of apoptotic cells, caspase-3 activation, and
      poly-ADP ribose polymerase (PARP) cleavage. Increased oxidative stress by using
      hydrogen peroxide also caused apoptosis. The changes due to TNF-alpha were
      associated with an increase in the inhibitor of kappaB kinase (IKK) and nuclear
      factor kappa-B (NF kappaB) phosphorylation. IL-10 by itself had no effect, but it
      prevented the above mentioned TNF-alpha-induced changes. Trolox also mitigated
      TNF-alpha induced changes. Pre-exposure of cells to an IKK inhibitor (PS-1145)
      prevented TNF-alpha-induced caspase-3 and PARP cleavage. Inhibition of ERK 1/2
      MAPK with PD98059 attenuated the protective role of IL-10 against TNF-alpha
      induced activation of IKK and NF kappaB as well as cardiomyocyte apoptosis.
      CONCLUSION: The present study shows that TNF-alpha-induced activation of the NF
      kappaB pathway plays a critical role in cardiomyocyte apoptosis. IL-10 prevents
      TNF-alpha-induced NF kappaB activation and pro-apoptotic changes in
      cardiomyocytes by inhibiting IKK phosphorylation through the activation of ERK
      1/2 MAPK.

PMID- 19181936
TI  - Delayed antibiotics for children with acute otitis media: is practice change
      sustainable?

PMID- 19181935
TI  - Endogenous testosterone attenuates neointima formation after moderate coronary
      balloon injury in male swine.
AB  - AIMS: Previous studies from our laboratory have demonstrated that testosterone
      increases coronary smooth muscle protein kinase C delta (PKC delta) both in vivo
      and in vitro and inhibits coronary smooth muscle proliferation by inducing
      G(0)/G(1) cell cycle arrest in a PKC delta-dependent manner. The purpose of the
      present study was to determine whether endogenous testosterone limits coronary
      neointima (NI) formation in a porcine model of post-angioplasty restenosis.
      METHODS AND RESULTS: Sexually mature, male Yucatan miniature swine were either
      left intact (IM), castrated (CM), or castrated with testosterone replacement
      (CMT; Androgel, 10 mg/day). Angioplasty was performed in both the left anterior
      descending and left circumflex coronary arteries with balloon catheter
      overinflation to induce either moderate (1.25-1.3 x diameter; 3 x 30 s) or severe
      (1.4x diameter; 3 x 30 s) injury, and animals were allowed to recover for either
      10 or 28 days. Injured coronary sections were dissected, fixed, stained (Verheoff
      Van Gieson, Ki67, PKC delta, p27), and analysed. Vessels without internal elastic
      laminal rupture were excluded. Following moderate injury, intimal area, intima-to
      media ratio (I/M), and I/M normalized to rupture index (RI) were increased in CM
      compared with IM and CMT. RI, medial area, and intimal/medial thickness (IMT)
      were not different between groups. NI formation was inversely related to serum
      testosterone concentration. Conversely, following severe injury, there were no
      significant differences between the groups. Testosterone inhibited proliferation
      and stimulated PKC delta and p27(kip1) expression during NI formation (10 days
      post-injury). CONCLUSION: These findings demonstrate that endogenous testosterone
      limits coronary NI formation in male swine and provides support for a protective
      role for testosterone in coronary vasculoproliferative diseases, such as
      restenosis and atherosclerosis.

PMID- 19181937
TI  - Practice corner: should we screen all patients starting chemotherapy for chronic
      hepatitis B virus infection?

PMID- 19181938
TI  - Evidence in context: one person's poison is another's acceptable risk.

PMID- 19181939
TI  - Letter: self-monitoring of blood glucose--caution warranted.

PMID- 19181940
TI  - Review: medication adjustment based on fractional exhaled nitric oxide did not
      prevent asthma exacerbations.

PMID- 19181941
TI  - Benefits of early intensive glucose control to prevent diabetes complications
      were sustained for up to 10 years.

PMID- 19181942
TI  - Benefits of tight blood pressure control to prevent diabetes complications were
      not sustained.

PMID- 19181943
TI  - A combination of telmisartan and ramipril increased renal outcomes in vascular
      disease or diabetes.

PMID- 19181944
TI  - General practitioners' advice to use topical rather than oral ibuprofen resulted
      in equivalent effects on chronic knee pain.

PMID- 19181945
TI  - Alexander technique lessons were effective for chronic or recurrent back pain at
      1 year.

PMID- 19181946
TI  - Review: daily salmeterol increases non-fatal serious adverse events in chronic
      asthma.

PMID- 19181947
TI  - Review: faecal occult blood test screening reduces risk of colorectal cancer
      mortality.

PMID- 19181948
TI  - CD4+ count-guided antiretroviral therapy interruption increased opportunistic
      disease and death more than continuous therapy in HIV.

PMID- 19181949
TI  - Active management of risk in pregnancy at term did not reduce caesarean delivery
      rates.

PMID- 19181950
TI  - Review: postmenopausal hormone therapy increases risk of stroke and venous
      thromboembolism but not coronary heart disease events.

PMID- 19181951
TI  - Review: an early invasive strategy has similar benefits in men and women with
      NSTEMI or unstable angina.

PMID- 19181952
TI  - A single measure of urinary neutrophil gelatinase-associated lipocalin was
      accurate for diagnosing acute kidney injury.

PMID- 19181953
TI  - Review: people with epilepsy have higher risk of death by drowning than the
      general population.

PMID- 19181954
TI  - Review: vasomotor symptoms peak at 1 year after final menstrual period and may
      persist for many years.

PMID- 19181955
TI  - Excess mortality after HIV seroconversion has greatly decreased in the past 10
      years.

PMID- 19181956
TI  - Physician training in the use of a decision aid increased patient participation
      in decision making for CVD prevention.

PMID- 19181957
TI  - The San Francisco Syncope Rule did not accurately predict serious short-term
      outcome in patients with syncope.

PMID- 19181958
TI  - The Paediatric Appendicitis Score (PAS) was useful in children with acute
      abdominal pain.

PMID- 19181959
TI  - The Splenoportal Index accurately predicted the presence of oesophageal varices
      in compensated cirrhosis.

PMID- 19181960
TI  - Dietary fish oil is antihypertrophic but does not enhance postischemic myocardial
      function in female mice.
AB  - Clinically and experimentally, a case for omega-3 polyunsaturated fatty acid
      (PUFA) cardioprotection in females has not been clearly established. The goal of
      this study was to investigate whether dietary omega-3 PUFA supplementation could
      provide ischemic protection in female mice with an underlying genetic
      predisposition to cardiac hypertrophy. Mature female transgenic mice (TG) with
      cardiac-specific overexpression of angiotensinogen that develop normotensive
      cardiac hypertrophy and littermate wild-type (WT) mice were fed a fish oil
      derived diet (FO) or PUFA-matched control diet (CTR) for 4 wk. Myocardial
      membrane lipids, ex vivo cardiac performance (intraventricular balloon) after
      global no-flow ischemia and reperfusion (15/30 min), and reperfusion arrhythmia
      incidence were assessed. FO diet suppressed cardiac growth by 5% and 10% in WT
      and TG, respectively (P < 0.001). The extent of mechanical recovery [rate
      pressure product (RPP) = beats/min x mmHg] of FO-fed WT and TG hearts was similar
      (50 +/- 7% vs. 45 +/- 12%, 30 min reperfusion), and this was not significantly
      different from CTR-fed WT or TG. To evaluate whether systemic estrogen was
      masking a protective effect of the FO diet, the responses of ovariectomized (OVX)
      WT and TG mice to FO dietary intervention were assessed. The extent of mechanical
      recovery of FO-fed OVX WT and TG (RPP, 50 +/- 4% vs. 64 +/- 8%) was not enhanced
      compared with CTR-fed mice (RPP, 60 +/- 11% vs. 80 +/- 8%, P = 0.335). Dietary FO
      did not suppress the incidence of reperfusion arrhythmias in WT or TG hearts
      (ovary-intact mice or OVX). Our findings indicate a lack of cardioprotective
      effect of dietary FO in females, determined by assessment of mechanical and
      arrhythmic activity postischemia in a murine ex vivo heart model.

PMID- 19181961
TI  - Stem cell homing and angiomyogenesis in transplanted hearts are enhanced by
      combined intramyocardial SDF-1alpha delivery and endogenous cytokine signaling.
AB  - We used a heterotopic transplanted working heart model to probe the collaborative
      role of bone marrow-derived progenitor cells (BPCs) and stromal cell-derived
      factor (SDF)-1alpha in attenuating tissue remodeling in recipient and
      transplanted hearts. BPCs from male transgenic rats expressing green fluorescent
      protein (GFP(+) BPCs, 2 x 10(6) cells) were injected intravenously into
      myeloablated female rats. One month later, heterotopic heart transplantation was
      performed. The left anterior descending coronary artery (LAD) of the recipient
      heart was occluded permanently. Mesenchymal stem cells (MSCs; 2 x 10(6) cells)
      with a null gene (null group) or overexpressing SDF-1alpha (SDF-1alpha group)
      were injected intramyocardially in the LAD perfusion region of both recipient and
      transplanted hearts. Recipient and transplanted hearts (n = 10 hearts/group) were
      harvested 21 days later for analysis. The survival of transplanted hearts was
      assessed daily by palpation in additional animals (n = 7). Five days after LAD
      occlusion, subpopulations of GFP(+) BPCs in the circulation were significantly
      higher in the SDF-1alpha group. Y chromosome, 5-bromo-2'-deoxyuridine, Ki67
      positive nuclei, newly formed vessels, and GFP(+) cells significantly increased
      in transplanted hearts of the SDF-1alpha group at 21 days after the injection of
      MSCs overexpressing SDF-1alpha, whereas fewer TUNEL-positive nuclei were found.
      The survival of transplanted hearts was also markedly increased in the SDF-1alpha
      group (P < 0.05). Supplementation of endogenous cytokines released from the
      ischemic myocardium with exogenous MSCs overexpressing SDF-1alpha significantly
      increased BPC homing to acutely ischemic recipient and progressively ischemic
      transplanted hearts. BPC recruitment resulted in the regeneration of new
      cardiomyocytes and blood vessels and extended survival of the transplanted
      hearts.

PMID- 19181962
TI  - Inhibition of Rho-dependent kinases ROCK I/II activates VEGF-driven retinal
      neovascularization and sprouting angiogenesis.
AB  - Vascular endothelial growth factor (VEGF) is an endothelial-specific growth
      factor that activates the small GTPase RhoA. While the role of RhoA for VEGF
      driven endothelial migration and angiogenesis has been studied in detail, the
      function of its target proteins, the Rho-dependent kinases ROCK I and II, are
      controversially discussed. Using the mouse model of oxygen-induced proliferative
      retinopathy, ROCK I/II inhibition by H-1152 resulted in increased angiogenesis.
      This enhanced angiogenesis, however, was completely blocked by the VEGF-receptor
      antagonist PTK787/ZK222584. Loss-of-function experiments in endothelial cells
      revealed that inhibition of ROCK I/II using the pharmacological inhibitor H-1152
      and ROCK I/II-specific small-interfering RNAs resulted in a rise of VEGF-driven
      sprouting angiogenesis. These functional data were biochemically substantiated by
      showing an enhanced VEGF-receptor kinase insert domain receptor phosphorylation
      and extracellular signal-regulated kinase 1/2 activation after inhibition of ROCK
      I/II. Thus our data identify that the inhibition of Rho-dependent kinases ROCK
      I/II activates angiogenesis both, in vitro and in vivo.

PMID- 19181963
TI  - Impaired vascular function in mice with an active cytomegalovirus infection.
AB  - Human cytomegalovirus (CMV) is implicated in vascular complications through
      endothelial dysfunction. However, the effect of in vivo infections on vascular
      function in isolated arteries has not been examined. In pregnancy, systemic and
      uterine vascular adaptations accommodate increased blood volume through several
      mechanisms, including decreased sensitivity to vasoconstrictors and increased
      production of endothelial-dependent vasodilators. We hypothesized that an active
      in vivo CMV infection would reduce vasodilation of isolated arteries to the
      endothelial-dependent vasodilator methacholine and increase vasoconstriction to
      the alpha(1)-adrenergic receptor agonist phenylephrine and that these CMV-induced
      changes would be accentuated in late pregnancy. A mouse CMV infection model was
      used to study vascular responses in isolated mesenteric and uterine arteries from
      nonpregnant and late pregnant mice. In the mouse, CMV is not transmitted to the
      fetus. Accordingly, there was no evidence of active infection in any fetus
      examined, even though an active infection was found in salivary glands, uterine
      and mesenteric arteries, and placentas. Contrary to our hypothesis, increased
      endothelial-dependent vasodilation was found in mesenteric arteries from infected
      compared with uninfected nonpregnant and pregnant mice These data implicate
      active CMV infections in hypotensive disorders. Similarly, increased vasodilation
      was found in uterine arteries from infected vs. uninfected nonpregnant mice.
      However, this was completely reversed in infected compared with uninfected late
      pregnant mice in which vasodilation in uterine arteries was significantly
      reduced. Uterine arteries from infected pregnant mice also showed increased
      vasoconstriction to phenylephrine. Maternal infection led to decreased placental
      weights but had no effect on fetal weights in late pregnancy. These novel data
      demonstrate abnormal systemic and uterine vascular responses during an active CMV
      infection in both nonpregnant and late pregnant mice. Importantly, despite
      reduced placental weights, fetal weights were maintained, suggesting effective
      intrauterine compensation in the mouse model.

PMID- 19181964
TI  - Adult progenitor cell transplantation influences contractile performance and
      calcium handling of recipient cardiomyocytes.
AB  - Adult progenitor cell transplantation has been proposed for the treatment of
      heart failure, but the mechanisms effecting functional improvements remain
      unknown. The aim of this study was to test the hypothesis that, in failing hearts
      treated with cell transplantation, the mechanical properties and excitation
      contraction coupling of recipient cardiomyocytes are altered. Adult rats
      underwent coronary artery ligation, leading to myocardial infarction and chronic
      heart failure. After 3 wk, they received intramyocardial injections of either
      10(7) green fluorescence protein (GFP)-positive bone marrow mononuclear cells or
      5 x 10(6) GFP-positive skeletal myoblasts. Four weeks after injection, both cell
      types increased ejection fraction and reduced cardiomyocyte size. The
      contractility of isolated GFP-negative cardiomyocytes was monitored by sarcomere
      shortening assessment, Ca(2+) handling by indo-1 and fluo-4 fluorescence, and
      electrophysiology by patch-clamping techniques. Injection of either bone marrow
      cells or skeletal myoblasts normalized the impaired contractile performance and
      the prolonged time to peak of the Ca(2+) transient observed in failing
      cardiomyocytes. The smaller and slower L-type Ca(2+) current observed in heart
      failure normalized after skeletal myoblast, but not bone marrow cell,
      transplantation. Measurement of Ca(2+) sparks suggested a normalization of
      sarcoplasmic reticulum Ca(2+) leak after skeletal myoblast transplantation. The
      increased Ca(2+) wave frequency observed in failing myocytes was reduced by
      either bone marrow cells or skeletal myoblasts. In conclusion, the morphology,
      contractile performance, and excitation-contraction coupling of individual
      recipient cardiomyocytes are altered in failing hearts treated with adult
      progenitor cell transplantation.

PMID- 19181965
TI  - Hypertensive state, independent of hypertrophy, exhibits an attenuated decrease
      in systolic function on cardiac kappa-opioid receptor stimulation.
AB  - Opioids/opiates are commonly administered to alleviate pain, unload the heart, or
      decrease breathlessness in patients with advanced heart failure. As such, it is
      important to evaluate whether the myocardial opioidergic system is altered in
      cardiac disease. A hamster model of spontaneous hypertension was investigated
      before the development of hypertension (1 mo of age) and in the hypertensive
      state (10 mo of age) to evaluate the effect of prolonged hypertension on
      myocardial opioidergic activity. Plasma beta-endorphin was decreased before the
      development of hypertension and in the hypertensive state (P < 0.05). There was
      no change in cardiac beta-endorphin content at either time point. No differences
      were detected in cardiac or plasma dynorphin A, Met-enkephalin, or Leu
      enkephalin, or in cardiac peptide expression of kappa- or delta-opioid receptors.
      mu-Opioid receptor was not detected in either model. To determine how
      hypertension affects myocardial opioid signaling, the ex vivo work-performing
      heart was used to assess the cardiac response to opioid administration in healthy
      hearts and those subjected to chronic hypertension. Agonists selective for the
      kappa- and delta-opioid receptors, but not mu-opioid receptors, induced a
      concentration-dependent decrease in cardiac function. The decrease in left
      ventricular systolic pressure on administration of the kappa-opioid receptor
      selective agonist, U50488H, was attenuated in hearts from hamsters subjected to
      chronic, untreated hypertension (P < 0.05) compared with control. These results
      show that peripheral and myocardial opioid expression and signaling are altered
      in hypertension.

PMID- 19181966
TI  - Restoration of contractility in hyperhomocysteinemia by cardiac-specific deletion
      of NMDA-R1.
AB  - Homocysteine (HCY) activated mitochondrial matrix metalloproteinase-9 and led to
      cardiomyocyte dysfunction, in part, by inducing mitochondrial permeability (MPT).
      Treatment with MK-801 [N-methyl-d-aspartate (NMDA) receptor antagonist]
      ameliorated the HCY-induced decrease in myocyte contractility. However, the role
      of cardiomyocyte NMDA-receptor 1 (R1) activation in hyperhomocysteinemia (HHCY)
      leading to myocyte dysfunction was not well understood. We tested the hypothesis
      that the cardiac-specific deletion of NMDA-R1 mitigated the HCY-induced decrease
      in myocyte contraction, in part, by decreasing nitric oxide (NO). Cardiomyocyte
      specific knockout of NMDA-R1 was generated using cre/lox technology. NMDA-R1
      expression was detected by Western blot and confocal microscopy. MPT was
      determined using a spectrophotometer. Myocyte contractility and calcium
      transients were studied using the IonOptix video-edge detection system and fura 2
      AM loading. We observed that HHCY induced NO production by agonizing NMDA-R1.
      HHCY induced the MPT by agonizing NMDA-R1. HHCY caused a decrease in myocyte
      contractile performance, maximal rate of contraction and relaxation, and
      prolonged the time to 90% peak shortening and 90% relaxation by agonizing NMDA
      R1. HHCY decreased contraction amplitude with the increase in calcium
      concentration. The recovery of calcium transient was prolonged in HHCY mouse
      myocyte by agonizing NMDA-R1. It was suggested that HHCY increased mitochondrial
      NO levels and induced MPT, leading to the decline in myocyte mechanical function
      by agonizing NMDA-R1.

PMID- 19181967
TI  - Longevity is associated with increased vascular resistance to high glucose
      induced oxidative stress and inflammatory gene expression in Peromyscus leucopus.
AB  - Vascular aging is characterized by increased oxidative stress and proinflammatory
      phenotypic alterations. Metabolic stress, such as hyperglycemia in diabetes, is
      known to increase the production of ROS and promote inflammatory gene expression,
      accelerating vascular aging. The oxidative stress hypothesis of aging predicts
      that vascular cells of long-lived species exhibit lower steady-state production
      of ROS and/or superior resistance to the prooxidant effects of metabolic stress.
      We tested this hypothesis using two taxonomically related rodents, the white
      footed mouse (Peromyscus leucopus) and the house mouse (Mus musculus), which show
      a more than twofold difference in maximum lifespan potential (8.2 and 3.5 yr,
      respectively). We compared interspecies differences in steady-state and high
      glucose (HG; 30 mmol/l)-induced production of O(2)(*-) and H(2)O(2), endothelial
      function, mitochondrial ROS generation, and inflammatory gene expression in
      cultured aortic segments. In P. leucopus aortas, steady-state endothelial O(2)(*
      ) and H(2)O(2) production and ROS generation by mitochondria were less than in M.
      musculus vessels. Furthermore, vessels of P. leucopus were more resistant to the
      prooxidant effects of HG. Primary fibroblasts from P. leucopus also exhibited
      less steady-state and HG-induced ROS production than M. musculus cells. In M.
      musculus arteries, HG elicited significant upregulation of inflammatory markers
      (TNF-alpha, IL-6, ICAM-1, VCAM, and monocyte chemoattractant protein-1). In
      contrast, the proinflammatory effects of HG were blunted in P. leucopus vessels.
      Thus, increased life span potential in P. leucopus is associated with decreased
      cellular ROS generation and increased resistance to prooxidant and
      proinflammatory effects of metabolic stress, which accord with predictions of the
      oxidative stress hypothesis of aging.

PMID- 19181968
TI  - Anterior cruciate ligament reconstruction with use of a single or double-bundle
      technique in patients with generalized ligamentous laxity.
AB  - BACKGROUND: In a patient with generalized ligamentous laxity, the risk of
      instability is greater with a conventionally reconstructed anterior cruciate
      ligament. The purpose of this study was to compare the clinical outcome of
      anterior cruciate ligament reconstruction done with a double-bundle technique
      with use of a quadriceps tendon-bone autograft and that of a single-bundle
      reconstruction with use of a bone-patellar tendon-bone autograft in patients with
      generalized ligamentous laxity. METHODS: The records of sixty-one patients who
      underwent anterior cruciate ligament reconstruction between June 2002 and October
      2005 were evaluated. Thirty-two patients underwent a single-bundle reconstruction
      (group 1), and twenty-nine patients underwent a double-bundle reconstruction
      (group 2). Clinical outcomes were determined from data obtained before surgery
      and at the twenty-four-month follow-up visit. RESULTS: Postoperatively, the mean
      side-to-side difference (and standard deviation) in anterior tibial translation,
      measured with use of a KT-2000 arthrometer, was greater for group 1 (3.37 +/-
      1.76 mm; range, 1.00 to 8.00 mm) than for group 2 (2.03 +/- 1.11 mm; range, 0.00
      to 3.50 mm) (p = 0.02). Three patients in group 1 had a grade-1+ pivot shift,
      while no patient in group 2 had an abnormal pivot shift. The mean score on the
      Hospital for Special Surgery knee ligament questionnaire was 90.8 in group 1 and
      92.1 in group 2, and the mean Lysholm score was 89.4 in group 1 and 91.1 in group
      2. CONCLUSIONS: On the basis of the evaluation of ligamentous laxity measured by
      the KT-2000 arthrometer, a double-bundle anterior cruciate ligament
      reconstruction with use of a quadriceps tendon-bone autograft allows less
      anterior translation than does a single-bundle reconstruction with use of a bone
      patellar tendon-bone autograft. However, we could not identify a significant
      difference in the functional outcome between the two techniques.

PMID- 19181969
TI  - Treatment with and without initial stabilizing surgery for primary traumatic
      patellar dislocation. A prospective randomized study.
AB  - BACKGROUND: There is no consensus about the management of acute primary traumatic
      patellar dislocation in young physically active adults. The objective of this
      study was to compare the clinical outcomes after treatment with and without
      initial stabilizing surgery for primary traumatic patellar dislocation in young
      adults. METHODS: Forty young adults, thirty-seven men and three women with a
      median age of twenty years (range, nineteen to twenty-two years), who had an
      acute primary traumatic patellar dislocation were randomly allocated to be
      treated with initial surgical stabilization (eighteen patients, with each
      receiving one of two types of initial stabilizing procedures) or to be managed
      with an orthosis (twenty-two patients, including four who had osteochondral
      fragments removed arthroscopically). After a median of seven years, thirty-eight
      patients returned for a follow-up examination. Redislocations, subjective
      symptoms, and functional limitations were evaluated. Radiographs and magnetic
      resonance images were obtained at the time of randomization, and twenty-nine
      (76%) patients underwent magnetic resonance imaging at the time of final follow
      up. RESULTS: A hemarthrosis as well as injuries of the medial retinaculum and the
      medial patellofemoral ligament were found on magnetic resonance imaging in all
      patients at the time of randomization. During the follow-up period, six of the
      twenty-one nonoperatively treated patients and none of the seventeen patients
      treated with surgical stabilization had a redislocation (p = 0.02). Four
      nonoperatively treated patients and two patients treated with surgical
      stabilization reported painful patellar subluxation. The median Kujala scores
      were 91 points for the surgically treated patients and 90 points for the
      nonoperatively treated patients. Thirteen patients in the surgically treated
      group and fifteen in the nonoperatively treated group regained their former
      physical activity level. At the time of follow-up, a full-thickness
      patellofemoral articular cartilage lesion was detected on magnetic resonance
      imaging in eleven patients; the lesions were considered to be unrelated to the
      form of treatment. CONCLUSIONS: In a study of young, mostly male adults with
      primary traumatic patellar dislocation, the rate of redislocation for those
      treated with surgical stabilization was significantly lower than the rate for
      those treated without surgical stabilization. However, no clear subjective
      benefits of initial stabilizing surgery were seen at the time of long-term follow
      up.

PMID- 19181970
TI  - The effect of a single infusion of zoledronic acid on early implant migration in
      total hip arthroplasty. A randomized, double-blind, controlled trial.
AB  - BACKGROUND: Aseptic loosening is the most frequent cause of implant failure in
      total hip arthroplasty. While a direct link between aseptic loosening and
      periprosthetic bone loss remains elusive, there is plentiful evidence for a close
      association with early implant migration. The present trial was primarily
      designed to evaluate whether a single infusion of 4 mg of zoledronic acid
      prevented early implant migration in patients with osteonecrosis of the femoral
      head. METHODS: Fifty patients were consecutively enrolled to receive either
      zoledronic acid or saline solution after cementless total hip arthroplasty.
      Radiographs, biochemical parameters of bone turnover, and the Harris hip-rating
      score were determined preoperatively and at each follow-up examination at seven
      weeks, six months, one year, and yearly thereafter. The median follow-up period
      was 2.8 years. RESULTS: We found a significant subsidence of the stem of up to a
      mean (and standard deviation) of -1.2 +/- 0.6 mm at two years within the control
      group, and the cups had a mean medialization of 0.6 +/- 1.0 mm and a mean
      cranialization of 0.6 +/- 0.8 mm (p < 0.001). Treatment with zoledronic acid
      effectively minimized the migration of the cups in both the transverse and the
      vertical direction (mean, 0.15 +/- 0.6 mm and 0.06 +/- 0.6 mm, respectively; p <
      0.05), while only a trend to decreased subsidence of the stem was detected.
      Finally, the Harris hip score rapidly increased over time in both treatment
      groups, although this increase was significantly more pronounced in the
      zoledronate-treated group than in the control group (analysis of variance, p =
      0.008). CONCLUSIONS: A single infusion of zoledronic acid shows promise in
      improving initial fixation of a cementless implant, which may improve the
      clinical outcome of total hip arthroplasty in patients with osteonecrosis of the
      femoral head.

PMID- 19181971
TI  - Humoral factors enhance fracture-healing and callus formation in patients with
      traumatic brain injury.
AB  - BACKGROUND: Scientific evidence is mounting for an association between traumatic
      brain injury and enhanced osteogenesis. The aim of this study was to correlate
      the in vitro osteoinductive potential of serum with the features of fracture
      healing and the extent of brain damage in patients with severe traumatic brain
      injury and bone fracture. METHODS: Patients with a long-bone fracture and a
      traumatic brain injury (seventeen patients) or without a brain injury (twenty
      four patients) were recruited. The Glasgow Coma Scale score was determined on
      admission. Radiographs of the fracture were made before surgery, at six weeks,
      and at three, six, and twelve months after surgery. The time to union was
      estimated clinically and radiographically, and the callus ratio to shaft diameter
      was calculated. Serum samples were collected at six, twenty-four, seventy-two,
      and 168 hours after injury, and their osteogenic potential was determined by
      measurement of the in vitro proliferation rate of the human fetal osteoblastic
      cell line hFOB1.19. RESULTS: Patients with a traumatic brain injury had a twofold
      shorter time to union (p = 0.01), a 37% to 50% increased callus ratio (p < 0.01),
      and their sera induced a higher proliferation rate in hFOB cells (p < 0.05). A
      linear relationship was revealed between hFOB cell proliferation rates and the
      amount of callus formed (p < 0.05). The Glasgow Coma Scale score was correlated
      with the callus ratio on both radiographic projections (p < 0.05), time to union
      (p = 0.04), and the proliferation rate of hFOB cells at six hours after injury (p
      = 0.03). CONCLUSIONS: Patients with a severe brain injury release unknown humoral
      factors into the blood circulation that enhance and accelerate fracture-healing.

PMID- 19181972
TI  - Shoulder strength in asymptomatic individuals with intact compared with torn
      rotator cuffs.
AB  - BACKGROUND: Normative data are essential to the evaluation of shoulder function.
      The purposes of this study were to establish a normative database of isometric
      shoulder strength measured in asymptomatic individuals verified to have intact
      rotator cuffs and to determine the effect of asymptomatic rotator cuff tears on
      shoulder strength. METHODS: Two hundred and thirty-seven volunteers with no
      shoulder pain or history of shoulder injury were screened with ultrasonography
      bilaterally for rotator cuff tears and then underwent isometric strength
      measurements for abduction in the scapular plane and external rotation.
      Statistical analysis was performed to evaluate the effect of age, body habitus,
      hand dominance, and the presence of a rotator cuff tear on shoulder strength.
      RESULTS: Of the 237 volunteers, forty-one were found to have a torn rotator cuff
      in at least one shoulder. The prevalence of rotator cuff tears was 0% for the
      subjects between forty and forty-nine years old; 10%, between fifty and fifty
      nine years old; 20%, between sixty and sixty-nine years old; and 40.7% for those
      seventy years old or older. Both abduction strength and external rotation
      strength in the male subjects showed an age-dependent decrease, whereas only
      abduction strength showed an age-dependent decrease in the female subjects. In
      multiple regression analysis, age and weight were the most important predictors
      of abduction strength and external rotation strength, respectively. In the
      shoulders with a large-to-massive full-thickness rotator cuff tear, abduction
      strength was significantly decreased (p = 0.007). Additionally, the ratio of
      abduction strength to external rotation strength was significantly decreased in
      the shoulders with a large-to-massive full-thickness tear compared with the
      shoulders with an intact rotator cuff (p < 0.001). CONCLUSIONS: There is a high
      prevalence of rotator cuff tears in elderly asymptomatic individuals.
      Asymptomatic shoulders with a large-to-massive full-thickness rotator cuff tear
      have significantly decreased abduction strength. When there is a substantial
      decrease in abduction strength in relation to external rotation strength, the
      presence of an asymptomatic full-thickness tear should be suspected in that
      shoulder. Previous studies establishing normative values for isometric shoulder
      strength may have been skewed by the presence of asymptomatic rotator cuff tears
      in elderly subgroups.

PMID- 19181973
TI  - Patient and surgeon radiation exposure: comparison of standard and mini-C-arm
      fluoroscopy.
AB  - BACKGROUND: Use of c-arm fluoroscopy is common in the operating room, outpatient
      clinic, and emergency department. Consequently, there is a concern regarding
      radiation exposure. Mini-c-arm fluoroscopes have gained popularity; however, few
      studies have quantified exposure during mini-c-arm imaging of a body part larger
      than a hand or wrist. The purpose of this study was to measure radiation exposure
      sustained by the patient and surgeon during the use of large and mini-c-arm
      fluoroscopy of an ankle specimen. METHODS: Standard and mini-c-arm fluoroscopes
      were used to image a cadaver ankle specimen, which was suspended on an adjustable
      platform. Dosimeters were mounted at specific positions and angulations to detect
      direct and scatter radiation. Testing was conducted under various scenarios that
      altered the proximity of the specimen and the radiation source. We attempted to
      capture a range of exposure data under conditions ranging from a best to a worst
      case scenario, as one may encounter in a procedural setting. RESULTS: With all
      configurations tested, measurable exposure during use of the large-c-arm
      fluoroscope was considerably higher than that during use of the mini-c-arm
      fluoroscope. Patient and surgeon exposure was notably amplified when the specimen
      was positioned closer to the x-ray source. The exposure values that we measured
      during ankle fluoroscopy were consistently higher than the exposure values that
      have been recorded previously during hand or wrist imaging. CONCLUSIONS: Exposure
      of the patient and surgeon to radiation depends on the tissue density and the
      shape of the imaged extremity. Elevated exposure levels can be expected when
      larger body parts are imaged or when the extremity is positioned closer to the x
      ray source. When it is possible to satisfactorily image an extremity with use of
      the mini c-arm, it should be chosen over its larger counterpart.

PMID- 19181974
TI  - Acetabular cartilage delamination in femoroacetabular impingement. Risk factors
      and magnetic resonance imaging diagnosis.
AB  - BACKGROUND: Delamination of acetabular articular cartilage is a common
      abnormality in hips with femoroacetabular impingement. The purpose of the present
      study was to identify clinical and radiographic factors predisposing to
      delamination and to assess the diagnostic accuracy of magnetic resonance
      arthrography for the detection of these lesions. METHODS: Following a
      retrospective review of records, we determined that acetabular cartilage
      delamination had been present in twenty-eight of sixty-four hips that had
      undergone a surgical dislocation procedure for the treatment of femoroacetabular
      impingement. Multivariable logistic regression was performed to assess the
      correlation of radiographic findings (i.e., magnetic resonance imaging and
      computerized tomography findings) with the status of delamination. The
      preoperative interpretations of the magnetic resonance arthrograms for twenty
      seven hips that underwent surgical dislocation were reviewed to assess the
      accuracy of detecting delamination. At the time of surgery, nine of these twenty
      seven hips were found to have delamination. Magnetic resonance arthrography
      interpretations that did not correlate with operative findings were subjected to
      conspicuity assessment and error analysis. RESULTS: The rate of delamination of
      the acetabular cartilage as noted at the time of surgical dislocation was 44%
      (twenty-eight of sixty-four). Delamination was strongly associated with male sex
      and femoral sided signs of impingement; however, it was not associated with
      acetabular overcoverage (center-edge angle, >40 degrees) (odds ratio = 0.16; p <
      0.05). While there was no significant difference in the prevalence of labral
      lesions between groups, whenever labral and delamination lesions were found in
      the same hip, they were directly adjacent to one another. Preoperative magnetic
      resonance arthrography had a low sensitivity for delamination (22%) but had a
      high specificity (100%). Two-thirds of the delamination lesions were visible on
      retrospective review of these images when the reader was unblinded to the
      surgical findings. Delamination could most often be identified on the sagittal T1
      weighted image and on the proton-density sequences with fat saturation.
      DISCUSSION: There should be a high level of suspicion for articular cartilage
      delamination in men and in patients with primarily cam-type femoroacetabular
      impingement. Acetabular overcoverage may be protective against delamination.
      Preoperative high-quality magnetic resonance arthrograms should be carefully
      analyzed for evidence of delamination in this patient population.

PMID- 19181975
TI  - The clamshell osteotomy: a new technique to correct complex diaphyseal malunions.
AB  - BACKGROUND: The treatment of complex diaphyseal malunions is challenging,
      requiring extensive preoperative planning and precise operative technique. We
      have developed a simpler method to treat some of these deformities. METHODS: Ten
      patients with complex diaphyseal malunions (including four femoral and six tibial
      malunions) underwent a clamshell osteotomy. The indications for surgery included
      pain at adjacent joints and deformity. After surgical exposure, the malunited
      segment was transected perpendicular to the normal diaphysis proximally and
      distally. The transected segment was again osteotomized along its long axis and
      was wedged open, similar to opening a clamshell. The proximal and distal segments
      of the diaphysis were then aligned with use of an intramedullary rod as an
      anatomic axis template and with use of the contralateral extremity as a length
      and rotation template. The patients were assessed clinically and radiographically
      at a mean of thirty-one months (range, six to fifty-two months) after the
      osteotomy. RESULTS: Complete angular correction was achieved in each case; the
      amount of correction ranged from 2 degrees to 20 degrees in the coronal plane,
      from 0 degrees to 32 degrees in the sagittal plane, and from 0 degrees to 25
      degrees in the axial plane (rotation). Correction of length ranged from 0 to 5
      cm, and limb length was restored to within 2 cm in all patients. All osteotomy
      sites were healed clinically by six months. While no deep infections occurred,
      superficial wound dehiscence occurred in two patients along the approach for the
      longitudinal portion of the osteotomy, emphasizing the importance of careful soft
      tissue handling and patient selection. CONCLUSIONS: The clamshell osteotomy
      provides a useful way to correct many forms of diaphyseal malunion by realigning
      the anatomic axis of the long bone with use of a reamed intramedullary rod as a
      template. This technique provides an alternative that could decrease preoperative
      planning time and complexity as well as decrease the need for intraoperative
      osteotomy precision in a correctly chosen subset of patients with diaphyseal
      deformities.

PMID- 19181976
TI  - Surgical repair of acute and chronic tibialis anterior tendon ruptures.
AB  - BACKGROUND: Rupture of the tibialis anterior tendon is an uncommon disorder that
      can cause a substantial functional deficit as a result of loss of ankle
      dorsiflexion strength. We are not aware of any reports on a large clinical series
      of patients undergoing surgical repair of this injury. METHODS: Nineteen tibialis
      anterior tendon ruptures were surgically repaired in eighteen patients ranging in
      age from twenty-one to seventy-eight years. Early repair was performed for one
      traumatic and seven atraumatic ruptures three days to six weeks after the injury.
      Delayed reconstruction was performed for two traumatic and nine atraumatic
      ruptures that had been present for seven weeks to five years. Direct tendon
      repair was possible for four of the early repairs and three of the delayed
      reconstructions. An interpositional autogenous tendon graft was used for four
      early repairs and eight delayed reconstructions. Patients were reassessed
      clinically and with the American Orthopaedic Foot and Ankle Society hindfoot
      score at an average of 53.3 months after surgery. RESULTS: The average hindfoot
      score improved significantly from 55.5 points preoperatively to 93.6 points
      postoperatively. The surgical results did not appear to vary according to patient
      age, sex, or medical comorbidity. Complications requiring a second surgical
      procedure occurred in three patients. Recovery of functional dorsiflexion and
      improvement in gait was noted in eighteen of the nineteen cases. Ankle
      dorsiflexion strength was graded clinically as 5/5 in fifteen of the nineteen
      cases. Three patients regained 4/5 ankle dorsiflexion strength, and one patient
      had 3/5 strength with a poor clinical result. CONCLUSIONS: Surgical restoration
      of the function of the tibialis anterior muscle can be beneficial regardless of
      age, sex, medical comorbidity, or delay in diagnosis. Early surgical treatment
      may be less complicated than delayed treatment, and an intercalated free tendon
      graft and/or gastrocnemius recession may be necessary to achieve an appropriately
      tensioned and balanced repair.

PMID- 19181977
TI  - Arthroscopically detected intra-articular lesions associated with acute ankle
      fractures.
AB  - BACKGROUND: Anatomic surgical realignment of ankle fractures may still be
      associated with poor clinical outcomes, possibly as a result of occult intra
      articular injury. The aim of this study was to determine if the severity of an
      acute ankle fracture is correlated with an increased number of arthroscopically
      detected intra-articular chondral lesions. METHODS: We conducted a retrospective
      review of the medical charts on 283 ankle fractures that had been treated with
      open reduction and internal fixation and for which ankle arthroscopy had been
      routinely performed. The severity of the ankle fractures was categorized, with
      use of the arthroscopic findings derived from the operative reports as well as
      the findings on preoperative radiographs, according to the Lauge-Hansen criteria.
      RESULTS: Of the 283 patients, eighty-four (forty-four female and forty male) met
      our inclusion criteria. Chondral lesions were found in sixty-one patients (73%).
      Of seventeen fractures graded as pronation-external rotation or supination
      external rotation type I according to the Lauge-Hansen classification, fifteen
      were associated with one or no chondral lesion and two, with two or more chondral
      lesions. Of ten fractures graded as pronation-external rotation or supination
      external rotation type II, nine were associated with one or no chondral lesion
      and one, with two or more chondral lesions. Of fifty-six fractures graded as
      pronation-external rotation or supination-external rotation type IV, twenty-seven
      were associated with one or no chondral lesion and twenty-nine, with two or more
      chondral lesions. Type-IV pronation-external rotation and supination-external
      rotation ankle fractures were more likely to be associated with two or more
      chondral lesions than type-I fractures (odds ratio = 8.1, 95% confidence interval
      = 1.7 to 38.6; p = 0.0044) or type-II fractures (odds ratio = 9.7, 95% confidence
      interval = 1.1 to 81.5; p = 0.0172). CONCLUSIONS: Chondral lesions are commonly
      found after an acute ankle fracture. This retrospective study demonstrated that
      the number of intra-articular chondral lesions associated with the more severe
      ankle fracture patterns (pronation-external rotation and supination-external
      rotation type-IV fractures) was greater than the number associated with the less
      severe ankle fracture patterns.

PMID- 19181979
TI  - Revision of the acetabular component without cement. A concise follow-up, at
      twenty to twenty-four years, of a previous report.
AB  - We previously reported the results of the use of a cementless acetabular shell
      for revision total hip arthroplasty in 138 hips at a minimum of three, seven, and
      fifteen years postoperatively. The current report presents the long-term outcomes
      of this group at a minimum follow-up of twenty years. Since the last report, two
      additional hips required repeat revision, both for infection; no additional
      acetabular shell was loose. In the entire series to date, repeat acetabular
      revision was performed in twenty-one (15%) of the original 138 hips. Twenty of
      the twenty-one shells were well fixed at the time of repeat revision, and one had
      become aseptically loose. The most common reasons for repeat revision were
      infection (eight hips) and recurrent instability (eight hips). In the metal
      shells that were well fixed, an isolated liner change for polyethylene wear
      and/or osteolysis was performed in a total of six hips; four of these liner
      exchanges were performed since the time of our last report. A liner change had
      been recommended because of severe wear in four additional hips; thus, 18% of the
      fifty-six unrevised metal shells were associated with polyethylene wear-related
      problems. Survivorship, with revision of the shell for aseptic loosening or
      radiographic evidence of loosening as the end point, was 95% at twenty years (95%
      confidence interval, 83% to 98%). Reoperations for wear and osteolysis were first
      seen at approximately twelve years postoperatively. At the time of the present
      long-term follow-up, the reoperation rate for polyethylene wear and/or osteolysis
      had increased. We continue to use a hemispherical, titanium metal shell with
      multiple screws for fixation in the majority of acetabular revisions.

PMID- 19181978
TI  - Treatment of osteonecrosis of the humeral head with cementless surface
      replacement arthroplasty.
AB  - BACKGROUND: Osteonecrosis of the humeral head is a disabling condition that can
      lead to joint destruction with persistent pain and dysfunction. The aim of the
      present study was to examine cementless humeral surface replacement arthroplasty
      as a treatment option for posttraumatic and nontraumatic osteonecrosis. METHODS:
      Between 2002 and 2005, seventeen shoulders with posttraumatic (n = 8) or
      nontraumatic (n = 9) osteonecrosis of the humeral head were treated with
      cementless humeral replacement arthroplasty. The mean proportion of the humeral
      head that was occupied by necrotic bone was 18.6% (range, 8.9% to 30.9%). The
      mean duration of follow-up was three years. Constant scores, patient
      satisfaction, and complications were recorded. Volumetric measurements of the
      necrotic areas and signs of implant loosening were analyzed with use of
      standardized radiographs. RESULTS: The mean Constant score for the entire cohort
      improved significantly from 31 to 62 points (34% to 75% when adjusted by age and
      sex) (p < 0.0001). There were also significant improvements in mean shoulder
      flexion (from 87 degrees to 139 degrees), abduction (from 64 degrees to 120
      degrees), and external rotation (from 2 degrees to 27 degrees). The final values
      for the Constant score, abduction, and power were significantly higher for the
      nontraumatic group than for the posttraumatic group. Fourteen patients (fifteen
      shoulders) were very satisfied (eleven shoulders) or satisfied (four shoulders),
      and two patients (two shoulders) were somewhat disappointed with the
      postoperative result. Signs of implant loosening were not observed. One patient
      had a wound infection that required surgical debridement and antibiotic therapy.
      To date, no implant revisions have been necessary. CONCLUSIONS: Cementless
      humeral surface replacement arthroplasty is a potentially bone-preserving option
      for patients with posttraumatic and nontraumatic osteonecrosis of the humeral
      head. Even in the presence of bone loss of as much as 31% of the humeral head,
      implant loosening was not observed. Good functional results and relief of pain in
      combination with a low complication rate can be achieved in the short term.

PMID- 19181980
TI  - Brace evaluation in children with diplegic cerebral palsy with a jump gait
      pattern.
AB  - BACKGROUND: Brace prescription for children with diplegic cerebral palsy
      challenges the clinician with a variety of options and little evidence for
      rational decisions. Previous studies have indicated that ankle-foot orthoses
      improve toe-walking, but it is unclear if any brace is better than another. The
      goal of the present study was to compare the effectiveness of hinged and dynamic
      ankle-foot orthoses in terms of improving gait and motor function in a
      homogeneous group of children with diplegic cerebral palsy exhibiting a jump gait
      pattern. METHODS: Fifteen children (mean age, 7.5 years) with spastic diplegic
      cerebral palsy who were able to walk independently with a jump gait pattern and
      twenty children (mean age, 10.6 years) with normal gait participated in the
      study. Standardized Gross Motor Function Classification System scores, Pediatric
      Outcomes Data Collection Instrument scores, and gait data were collected,
      analyzed, and compared. The subjects were tested while barefoot and while wearing
      hinged and dynamic ankle-foot orthoses. Data were analyzed to detect differences
      among these conditions. RESULTS: Significant improvements in gait metrics were
      seen during brace wear. No significant differences were seen between the two
      different braces used. The barefoot and braced conditions differed most
      significantly in terms of ankle kinematics and kinetics. Among the patients with
      cerebral palsy, no significant differences in the standardized outcome
      measurements were found between the braced and unbraced conditions or between the
      two braced conditions. CONCLUSIONS: Our data suggest that gait improves with
      brace wear in children with cerebral palsy with a level-I Gross Motor Function
      Classification System score. The Pediatric Outcomes Data Collection Instrument
      and the Gross Motor Function Measure were not sensitive to brace treatment in the
      population studied. The hinged and dynamic braces were equally effective for
      improving ankle kinematics and kinetics in these relatively highly functioning
      children with cerebral palsy.

PMID- 19181981
TI  - Gene expression in slipped capital femoral epiphysis. Evaluation with laser
      capture microdissection and quantitative reverse transcription-polymerase chain
      reaction.
AB  - BACKGROUND: Slipped capital femoral epiphysis is a poorly understood condition
      affecting adolescents. Prior studies have suggested that the etiology may be
      related to abnormal collagen in the growth plate cartilage, but we are not aware
      of any investigations analyzing collagen or other structural proteins on a
      molecular level in the affected tissue. This study was performed to evaluate
      expression of mRNA for key structural molecules in growth plate chondrocytes of
      patients with slipped capital femoral epiphysis. METHODS: A core biopsy of the
      proximal femoral physis was performed in nine patients with slipped capital
      femoral epiphysis, and the specimens were compared with five specimens from the
      normal distal femoral and proximal tibial and fibular physes of age-matched
      patients treated surgically for a limb-length inequality. We utilized laser
      capture microdissection techniques followed by quantitative reverse transcription
      polymerase chain reaction analysis to determine if a change or abnormality in
      type-II-collagen and/or aggrecan gene expression may be associated with slipped
      capital femoral epiphysis. With these techniques, we correlated chondrocyte
      spatial location and gene expression to provide greater insight into this
      pathological condition and a more complete understanding of growth plate biology
      in general. RESULTS: Downregulation of both type-II collagen and aggrecan was
      found in the growth plates of the subjects with slipped capital femoral epiphysis
      when compared with the levels in the age-matched controls. In eight specimens
      from affected patients, the level of expression of type-II-collagen mRNA was, on
      the average (and standard error of the mean), 13.7% +/- 0.2% of that in four
      control specimens and the aggrecan level averaged only 26% +/- 0.2% of the
      control aggrecan level. CONCLUSIONS: The decreases that we identified in type-II
      collagen and aggrecan expression would affect the quantity, distribution, and
      organization of both components in a growth plate, but these changes could be
      associated with either the cause or the result of a slipped capital femoral
      epiphysis.

PMID- 19181982
TI  - Motion of the shoulder complex during multiplanar humeral elevation.
AB  - BACKGROUND: Many prior studies have evaluated shoulder motion, yet no three
      dimensional analysis comparing the combined clavicular, scapular, and humeral
      motion during arm elevation has been done. We aimed to describe and compare
      dynamic three-dimensional motion of the shoulder complex during raising and
      lowering the arm across three distinct elevation planes (flexion, scapular plane
      abduction, and coronal plane abduction). METHODS: Twelve subjects without a
      shoulder abnormality were enrolled. Transcortical pin placement into the
      clavicle, scapula, and humerus allowed electromagnetic motion sensors to be
      rigidly fixed. The subjects completed two repetitions of raising and lowering the
      arm in flexion, scapular, and abduction planes. Three-dimensional angles were
      calculated for sternoclavicular, acromioclavicular, scapulothoracic, and
      glenohumeral joint motions. Joint angles between humeral elevation planes and
      between raising and lowering of the arm were compared. RESULTS: General patterns
      of shoulder motion observed during humeral elevation were clavicular elevation,
      retraction, and posterior axial rotation; scapular internal rotation, upward
      rotation, and posterior tilting relative to the clavicle; and glenohumeral
      elevation and external rotation. Clavicular posterior rotation predominated at
      the sternoclavicular joint (average, 31 degrees). Scapular posterior tilting
      predominated at the acromioclavicular joint (average, 19 degrees). Differences
      between flexion and abduction planes of humerothoracic elevation were largest for
      the glenohumeral joint plane of elevation (average, 46 degrees). CONCLUSIONS:
      Overall shoulder motion consists of substantial angular rotations at each of the
      four shoulder joints, enabling the multiple-joint interaction required to elevate
      the arm overhead.

PMID- 19181983
TI  - Fractures of the capitellum and trochlea.
AB  - BACKGROUND: Recent work has established that apparently isolated fractures of the
      capitellum are often more complex and involve the lateral epicondyle, trochlea,
      and posterior aspect of the distal part of the humerus. We assessed the
      experience with operative stabilization of fractures of the capitellum and
      trochlea at one level-I trauma center over a twenty-eight-year period. METHODS:
      Thirty classifiable partial articular fractures involving the capitellum and
      trochlea were included in the study. Twenty-seven patients were followed for a
      minimum of twelve months, and fourteen patients returned for long-term follow-up
      at a median of seventeen years. The early and long-term results were evaluated
      according to the Broberg and Morrey Functional Rating Index. The long-term
      results were also evaluated according to the Mayo Elbow Performance Index (MEPI),
      the American Shoulder and Elbow Surgeons (ASES) score, and the Disabilities of
      the Arm, Shoulder and Hand (DASH) questionnaire. RESULTS: Eighteen patients (67%)
      had one or more subsequent surgical procedures, and eight of these patients had
      the procedure to address surgical complications. Five of the eight patients with
      complications and ten additional patients underwent routine removal of implants;
      these fifteen patients included twelve of the fourteen patients in the long-term
      cohort. In addition to the fracture of the distal part of the humerus, four
      patients had a dislocation of the elbow; three, a fracture of the olecranon or
      the proximal part of the ulna; and two, a fracture of the radial head. The median
      arc of flexion improved from 106 degrees at the time of early follow-up to 119
      degrees at the time of long-term follow-up (p < 0.05). In the group of fourteen
      patients with long-term follow-up, the median Broberg and Morrey score was 93
      points at the time of early follow-up and 95 points at the time of late follow
      up. The functional results were worse for patients with a Type-3 fracture, as
      classified with the system of Dubberley et al., than they were for those with a
      Type-1 fracture. The fourteen patients with long-term follow-up had a median MEPI
      of 98 points, a median ASES score of 88 points, and a median DASH score of 8
      points; nine of the fourteen patients had radiographic signs of arthrosis.
      CONCLUSIONS: The vast majority of what appear to be capitellar fractures are
      actually complex fractures of the articular surface involving both the capitellum
      and the trochlea. More complex fractures have worse functional results; however,
      the functional results of operative treatment seem to be durable over time.

PMID- 19181984
TI  - Video-assisted thoracoscopic spinal fusion compared with posterior spinal fusion
      with thoracic pedicle screws for thoracic adolescent idiopathic scoliosis.
AB  - BACKGROUND: Although the gold standard for the surgical treatment of thoracic
      adolescent idiopathic scoliosis has been posterior spinal fusion, video-assisted
      thoracoscopic surgery recently has become a viable alternative. In the treatment
      of structural thoracic curves, video-assisted thoracoscopic surgery has
      demonstrated outcomes equivalent to those of posterior spinal fusion with use of
      an all-hook or hybrid pedicle screw-hook construct. No study to date, however,
      has compared this technique with posterior spinal fusion with thoracic pedicle
      screws, which has become the current standard of care. METHODS: A matched-pair
      analysis of thirty-four consecutive patients (seventeen pairs) undergoing either
      video-assisted thoracoscopic surgery or posterior spinal fusion with thoracic
      pedicle screws for the treatment of structural scoliosis was performed; the study
      included eight male and twenty-six female patients with an average age of 15.0
      years. Pairs were matched according to curve type and magnitude, patient age, and
      sex. Clinical data, the results of the Scoliosis Research Society questionnaire,
      and radiographic data were collected preoperatively and at a minimum of two years
      postoperatively and were compared between the groups. RESULTS: Video-assisted
      thoracoscopic surgery was associated with significantly increased operative times
      (mean, 326 compared with 246 minutes; p = 0.033) and reduced blood loss (mean,
      371 compared with 1018 mL; p = 0.001), but there were no differences between the
      groups in terms of the transfusion rate (18% compared with 29%; p = 0.69) or the
      length of stay. The percentage correction of the major curve was 57.3% for the
      video-assisted thoracoscopic surgery group and 63.8% for the posterior spinal
      fusion group (p = 0.08). With the numbers available, no differences were detected
      in terms of the cephalad thoracic curve, caudad compensatory lumbar curve,
      coronal balance, thoracic kyphosis, lumbar lordosis, sagittal balance, end
      vertebra tilt angle, or angle of trunk rotation measurements preoperatively or at
      the time of the latest follow-up. The average number of fused levels was 5.9 in
      the video-assisted thoracoscopic surgery group and 8.9 in the posterior spinal
      fusion group (p < 0.001). Relative to the Cobb end vertebra, the most caudad
      instrumented vertebra was 0.81 level more cephalad in the video-assisted
      thoracoscopic surgery group as compared with the posterior spinal fusion group (p
      = 0.004). No significant differences were detected in any of the questionnaire
      outcomes at any time point. Although both groups experienced similar improvement
      from baseline in terms of pulmonary function at two years, the posterior spinal
      fusion group had significantly improved peak flow measurements (p = 0.04) in
      comparison with the video-assisted thoracoscopic surgery group. CONCLUSIONS: For
      single thoracic curves of <70 degrees in patients with a normal or hypokyphotic
      thoracic spine, video-assisted thoracoscopic surgery can produce equivalent
      radiographic results, patient-based clinical outcomes, and complication rates in
      comparison with posterior spinal fusion with thoracic pedicle screws, with the
      exception that posterior spinal fusion with thoracic pedicle screws may result in
      better major curve correction. The potential advantages of video-assisted
      thoracoscopic surgery over posterior spinal fusion with thoracic pedicle screws
      include reduced blood loss, fewer total levels fused, and the preservation of
      nearly one caudad fusion level, whereas the disadvantages include increased
      operative times and slightly less improvement in pulmonary function.

PMID- 19181985
TI  - Capsular and pericapsular contributions to acetabular and femoral head perfusion.
AB  - BACKGROUND: Capsular and pericapsular vessels are believed to contribute to
      acetabular and femoral head perfusion, but, to our knowledge, there is no
      anatomic study to support this theory. The purpose of this study was to describe
      the vascular anatomy of the hip with particular reference to the contributions of
      the capsular and pericapsular vessels. METHODS: Twenty fresh cadavers were
      dissected twenty-four hours after intra-arterial injection of colored silicone.
      The arteries supplying the hip were followed by careful dissection from their
      origins outside the pelvis to their terminal branches. Particular attention was
      paid to the vessels traveling between the acetabulum and the capsule and the
      femoral head. RESULTS: In all twenty specimens, the hip capsule received blood
      supply from the superior and inferior gluteal arteries proximally and from the
      medial and lateral femoral circumflex arteries distally. The contributory vessels
      entered the capsule peripherally and superficially. The circumflex arteries
      supplied the anterior capsule. The gluteal arteries supplied the posterior and
      posterosuperior aspect of the hip capsule, augmented by contributions from the
      circumflex arteries. Variable anastomoses were found between the gluteal and
      femoral systems on the capsular surface beneath the gluteus minimus and short hip
      external rotators. The medial femoral circumflex artery provided the dominant
      blood supply to the femoral head in eighteen specimens, and the inferior gluteal
      artery provided the dominant supply in two specimens. CONCLUSIONS: Capsular and
      pericapsular vessels that contribute to the blood supply of the acetabulum run on
      the posterior and posterolateral surface of the capsule. The dominant blood
      supply to the femoral head comes from vessels that approach the joint posteriorly
      and penetrate the joint near the femoral attachment of the capsule.

PMID- 19181987
TI  - Levels of evidence in research published in The Journal of Bone and Joint Surgery
      (American Volume) over the last thirty years.
AB  - BACKGROUND: The recent emphasis on evidence-based medicine has led to increasing
      levels of evidence being published in surgical journals. The purpose of the
      present study was to review the levels of evidence in reports published in The
      Journal of Bone and Joint Surgery (American Volume) over the last thirty years.
      METHODS: We reviewed all of the articles published in The Journal in the years
      1975, 1985, 1995, and 2005. Cadaver studies, animal studies, basic-science
      studies, review articles, Instructional Course Lectures, and correspondence were
      excluded. Articles were scored according to The Journal's levels of evidence for
      a primary research question. RESULTS: A total of 1058 articles were reviewed. Of
      these, 134, 123, 120, and 174 articles met the inclusion criteria for the years
      1975, 1985, 1995, and 2005, respectively, and were ranked according to level of
      evidence. The number of articles for each level of evidence rating was then
      expressed as a percentage of the total number of articles meeting the inclusion
      criteria for that year. There was a significant trend toward higher levels of
      evidence, with the combined percentage of Level-I, II, and III studies increasing
      from 17% to 52% (p < 0.01). The percentage of Level-I studies increased from 4%
      in 1975 to 21% in 2005. The average level of evidence rating improved from 3.72
      to 2.90 during the study period. CONCLUSIONS: The level of evidence in The
      Journal has improved significantly over the last thirty years.

PMID- 19181986
TI  - Soft-tissue resurfacing of the glenoid in the treatment of glenohumeral arthritis
      in active patients less than fifty years old.
AB  - BACKGROUND: Soft-tissue resurfacing of the glenoid, with arthroplasty of the
      humeral head, has been proposed as a viable treatment option for younger patients
      with symptomatic osteoarthritis of the shoulder. The purpose of this study was to
      evaluate our results with soft-tissue resurfacing of the glenoid in patients with
      glenohumeral arthritis who were less than fifty years of age, as we were
      concerned that this type of procedure was leading to poor outcomes. METHODS:
      Between 2000 and 2006, thirteen patients with an average age of thirty-four years
      underwent soft-tissue resurfacing of the glenoid and humeral head arthroplasty.
      Achilles tendon allograft was used in eleven patients; fascia lata autograft, in
      one; and anterior shoulder joint capsule, in one. Three patients had resurfacing
      of the humeral head with a stemless resurfacing implant, and ten patients had a
      hemiarthroplasty. The patients were followed for a minimum of two years or until
      failure, and the duration of follow-up averaged forty-eight months. The results
      were graded with a visual analog pain scale, the subjective shoulder value, and
      the Constant and Murley score. Radiographic review was performed in order to
      determine the degree of joint space loss and glenoid erosion. RESULTS: Ten of the
      thirteen patients required a revision total shoulder arthroplasty at a mean of
      fourteen months (range, six to thirty-four months) postoperatively. The principal
      reasons for revision were persistent pain and a decreased range of motion.
      Radiographic evaluation at the time of the revision surgery demonstrated loss of
      joint space and glenoid erosion in all cases. At the revision surgery, the
      allograft was found to be absent, and thick scar tissue, which may have been a
      graft remnant, was found at the perimeter of the glenoid. Of the three patients
      who did not have a revision arthroplasty, one had good function, pain relief, and
      an improved range of motion; however, the postoperative course of the other two
      was complicated by infection. One of them had a salvage with early irrigation and
      debridement as well as intravenous antibiotics, whereas the other underwent
      resection arthroplasty because of persistent infection. CONCLUSIONS: Soft-tissue
      resurfacing of the glenoid with an Achilles tendon allograft combined with
      humeral head arthroplasty is not a reliable method of treatment of glenohumeral
      arthritis in an active patient younger than fifty years of age, as the clinical
      outcome is poor. Moreover, we found no evidence that the graft acts as a durable
      bearing surface.

PMID- 19181988
TI  - Effect of radiofrequency energy on glenohumeral fluid temperature during shoulder
      arthroscopy.
AB  - BACKGROUND: Reports of glenohumeral chondrolysis following arthroscopy have
      raised concern about the deleterious effects that thermal devices may have on
      articular cartilage. The purpose of this study was to investigate the effects of
      flow and duration of treatment with a thermal device on temperatures within
      cadaveric glenohumeral joint specimens. It was hypothesized that the use of a
      thermal device during surgery increases the temperature of fluid within the joint
      to >45 degrees C, which has been shown to cause chondrocyte death. METHODS:
      Temperature was measured at four locations within ten cadaver shoulder joints.
      Eight heating trials were performed on each cadaver shoulder to test three
      variables: the method of heating (continuous or intermittent), the fluid-pump
      flow rate (no flow, 50% flow, or 100% flow), and the location of the
      radiofrequency probe (the radiofrequency energy was either applied directly to
      anterior capsular tissue in a paintbrush pattern or held adjacent to the glenoid
      without tissue contact). RESULTS: Temperatures of >45 degrees C occurred in every
      trial. The average maximum temperatures in all no-flow conditions were
      significantly higher than those in the trials with flow. Higher temperatures were
      measured by the anterior probe in all trials. When the heating had been applied
      adjacent to the glenoid, without tissue contact, the time needed to cool to a
      safe temperature was significantly longer in the no-flow states (average, 140.5
      seconds) than it was in the 50% flow states (average, 12.5 seconds) or the 100%
      flow states (average, 8.5 seconds). CONCLUSIONS: Use of a thermal probe during
      arthroscopy may cause joint fluid temperatures to reach levels high enough to
      cause chondrocyte death. Maintaining adequate fluid-pump flow rates may help to
      lower joint fluid temperatures and protect articular cartilage.

PMID- 19181989
TI  - Acute forearm compartment syndrome secondary to digit avulsion injury. A case
      report.

PMID- 19181990
TI  - Cervical stenosis and spastic quadriparesis in Morquio disease (MPS IV). A case
      report with twenty-six-year follow-up.

PMID- 19181991
TI  - Failure of metal-on-metal total hip arthroplasty mimicking hip infection. A
      report of two cases.

PMID- 19181992
TI  - Fractures of the clavicle.
AB  - Undisplaced fractures of both the diaphysis and the lateral end of the clavicle
      have a high rate of union, and the functional outcomes are good after
      nonoperative treatment. Nonoperative treatment of displaced shaft fractures may
      be associated with a higher rate of nonunion and functional deficits than
      previously reported. However, it remains difficult to predict which patients will
      have these complications. Since a satisfactory functional outcome may be obtained
      after operative treatment of a clavicular nonunion or malunion, there is
      currently considerable debate about the benefits of primary operative treatment
      of these injuries. Displaced lateral-end fractures have a higher risk of nonunion
      after nonoperative treatment than do shaft fractures. However, nonunion is
      difficult to predict and may be asymptomatic in elderly individuals. The results
      of operative treatment are more unpredictable than they are for shaft fractures.

PMID- 19181993
TI  - Adolescent shoulder injuries: consensus and controversies.

PMID- 19181994
TI  - Musculoskeletal research at the National Institute of Arthritis and
      Musculoskeletal and Skin Diseases: a snapshot.

PMID- 19181995
TI  - The need for increased access to the U.S. health-care system.

PMID- 19181997
TI  - The reproducibility and repeatability of varus stress radiographs in the
      assessment of isolated fibular collateral ligament and grade-III posterolateral
      knee injuries.

PMID- 19181998
TI  - The efficacy of combined popliteal and ankle blocks in forefoot surgery.

PMID- 19181999
TI  - Modes of wear after semiconstrained total elbow arthroplasty.

PMID- 19182000
TI  - Open rotator cuff repair without acromioplasty.

PMID- 19182003
TI  - Analysis of surgeon-controlled variables in the treatment of limb-threatening
      type-III open tibial diaphyseal fractures.

PMID- 19182004
TI  - Results of internal fixation of Pauwels type-3 vertical femoral neck fractures.

PMID- 19182007
TI  - Medial-wedge insoles improved pain and function in osteoarthritic knees with
      valgus deformity.

PMID- 19182008
TI  - Mini-open rotator cuff repair improved quality of life at 3 months.

PMID- 19182009
TI  - Computer-navigated and manual anterior cruciate ligament reconstructions were
      similar in function and stability outcomes.

PMID- 19182010
TI  - What's new in hand surgery.

PMID- 19182011
TI  - Advanced imaging and computer-assisted surgery of the knee and hip. Introduction.

PMID- 19182012
TI  - Section I: Setting the stage.

PMID- 19182013
TI  - Needs and opportunities in the assessment and treatment of osteoarthritis of the
      knee and hip: the view of the rheumatologist.
AB  - Osteoarthritis represents a major therapeutic challenge to medical and health
      care providers. In part, this is related to the limited tools that are available
      for assessing the structural state of joint tissues and to the lack of effective
      therapies to alter the natural history of osteoarthritis progression. From a
      clinical and pathologic perspective, osteoarthritis is not a homogeneous
      disorder, and the underlying pathogenic mechanisms differ among individuals. Even
      in the same individual, the pathologic processes and etiologic mechanisms may
      differ at specific stages of disease progression. In the development of
      strategies for effective intervention, several issues need to be considered.
      First, the stage of osteoarthritis progression must be considered. Therapies that
      are effective prior to the development of structural alterations may have limited
      utility in later stages. Similarly, treatments for late-stage osteoarthritis need
      to be adapted and adjusted to target specific symptoms that are amenable to
      modification. Despite the limited therapeutic options available for the treatment
      of osteoarthritis, there are interventions that have been shown to be beneficial.
      These include preventive strategies as well as specific interventions, such as
      the judicious use of analgesic medications for the control of pain. It is
      essential to develop an integrated multidisciplinary approach to osteoarthritis;
      this approach should be one that involves medical and surgical specialists as
      well as other health-care providers. In addition, further clinical and basic
      science research is needed so that improved and more effective therapies for
      osteoarthritis as well as better methods for monitoring and assessing the
      efficacy of treatment interventions can be developed.

PMID- 19182014
TI  - Perspectives on computer-assisted orthopaedic surgery: movement toward
      quantitative orthopaedic surgery.
AB  - The fundamental goal of computer-assisted surgery is to make orthopaedic surgery
      patient-specific, minimally invasive, and quantitative. The components of
      computer-assisted surgery include preoperative imaging and planning,
      intraoperative execution, and postoperative evaluation. Ideally, these components
      are integrated such that sophisticated diagnostic technologies are used to create
      a patient-specific surgical plan. This plan is then programmed into a computer
      assisted intraoperative system so that it can be precisely executed. Finally, the
      patient outcome is tracked longitudinally in a quantitative fashion. Computer
      assisted surgery relies on the use of quantitative data rather than surgeon feel
      and intuition to facilitate clinical decision-making. As surgeons rely more on
      quantitative feedback, they must establish appropriate specifications for various
      operations. These specifications should be clinically relevant and must have
      known targets and tolerances. This overview provides examples of quantitative
      surgery as applied in navigated total knee replacement and anterior cruciate
      ligament reconstruction and in the more recent indication of robotic unicondylar
      knee replacement. Computer-assisted surgery represents a set of tools that
      facilitate quantitative surgery. To effectively use these tools, however, one
      must identify technical specifications that are clinically relevant for the
      various procedures; these specifications must be associated with known target
      values and tolerances and must have the capability of being reliably measured by
      computer-assisted surgery tools. Clinical and basic-science research is necessary
      to better define technical specifications for navigated procedures.

PMID- 19182015
TI  - Challenges of technology integration and computer-assisted surgery.
AB  - The rapid progress of modern computerized capabilities has not been paralleled by
      a similar progress in the operating room setting and in operating techniques. The
      major advance in orthopaedic surgery during the past fifty years has been the
      introduction of intraoperative fluoroscopic imaging, while surgical techniques
      have remained mostly unchanged. Orthopaedic procedures dealing with bones--a
      nondeformable tissue--are suitable for computerized guidance based on
      preoperatively and intraoperatively obtained images. Computer-assisted surgery
      progressed from the first-generation systems of the 1990 s to the present third
      generation systems, enabling surgeons to implant a knee or hip prosthesis with
      high precision. However, most orthopaedic surgeons avoid using computer
      navigation surgical techniques. Why has the implementation of computer-assisted
      surgery procedures met so many hurdles and obstacles? The factors that make up
      the answer to this question can be grouped into three categories: human,
      technological, and financial. Computer-assisted surgery has the potential to
      revolutionize orthopaedic surgery just as fluoroscopy did a few decades ago;
      however, its widespread use has been hampered by a lack of sufficient clinical
      data on the one hand and by a reluctance to use the technique and thereby collect
      and share data on the other. The challenge is to overcome the human,
      technological, and financial hurdles. Once these obstacles are addressed, we
      believe that computer-assisted surgery will set a new standard of care. Until
      that time, some will be willing to lead the revolution and pay the price of
      progress, and others will be reluctant to take part in this endeavor.

PMID- 19182016
TI  - The challenges of clinical validation of emerging technologies: computer-assisted
      devices for surgery.
AB  - Over the last decade, the use of computers and robotics in medicine has increased
      commensurate with emergent advances in technology. This article largely focuses
      on the challenges that the U.S. Food and Drug Administration faces when
      evaluating new technologies for entry into the market. How different categories
      of devices are categorized and what types of data have been used for regulatory
      approval or clearance are described. These are compared with expectations that
      the clinical community may have for these devices. A brief discussion of current
      regulatory thinking about these types of devices is also included.

PMID- 19182017
TI  - Section II: Basic science issues in advanced musculoskeletal imaging and computer
      assisted surgery.

PMID- 19182018
TI  - Advantages of optical compared with electromagnetic tracking.
AB  - Tracking systems are critical to all types of computer-assisted image-guided
      intervention. Many technologies exist; however, only optical and electromagnetic
      systems are widely used commercially. In orthopaedic applications, optical
      systems dominate because of the large working volume and accuracy, but these
      systems suffer from deficiencies due to line of sight. Electromagnetic trackers
      can be made much smaller but are less accurate and are affected by metal,
      although current-generation systems are less affected by metal artifacts than
      were the earlier ones, which were more widely reported in the literature.

PMID- 19182019
TI  - Section III: Morphology, intraoperative imaging, and image processing.

PMID- 19182020
TI  - Correlations between joint morphology and pain and between magnetic resonance
      imaging, histology, and micro-computed tomography.
AB  - Chronic or recurrent pain in the knee is a central feature of osteoarthritis, and
      diagnostic imaging techniques that are used to evaluate osteoarthritis ideally
      should correlate with the amount of pain. However, consistent correlations have
      not been found between pain and radiographic and magnetic resonance imaging
      findings consistent with osteoarthritis (i.e., cartilaginous, ligamentous, and
      meniscal abnormalities) or between pain and radiographic grades that are used to
      assess osteoarthritis. On the other hand, an association between bone marrow
      edema pattern on magnetic resonance images and knee pain has been suggested. To
      better understand the evolution of osteoarthritis and the importance of imaging
      findings in relation to joint morphology and function, the histological basis of
      magnetic resonance imaging findings was studied and the adaptation processes of
      trabecular bone induced by osteoarthritis were analyzed. In addition to
      summarizing the current knowledge on pain and imaging findings, the current
      review presents available data that demonstrate the ability of noninvasive
      radiographic techniques to depict cartilage-bone interactions in patients with
      joint degeneration.

PMID- 19182021
TI  - Utility of intraoperative three-dimensional imaging at the hip and knee joints
      with and without navigation.
AB  - Intraoperative three-dimensional imaging in orthopaedic trauma care has achieved
      greater importance over the last few years in some specialized hospital centers.
      For various types of peripheral-extremity trauma, clinical studies have
      confirmed, on the basis of three-dimensional information, an intraoperative
      revision rate ranging from 7% to 19%. Three-dimensional C-arm imaging may be used
      to achieve adequate intraoperative information about the quality of fracture
      reduction, residual steps, and correct implant placement, and this technique has
      been described for use in both the hip joint (for acetabular fractures, isolated
      femoral head [Pipkin-type] fractures, three-dimensional navigated sacroiliac
      screw or acetabular column screw placements, and, less frequently, for navigated
      drilling of tumors or osteochondral lesions) and the knee joint (for tibial
      plateau fractures, complex distal femoral condylar fractures, and navigated
      targeting of osteochondral lesions in combination with the use of preoperative
      magnetic resonance imaging scans). Major limitations of this technology include
      increased intraoperative time requirements, limited image quality compared with
      that of computed tomographic scans, cost, specific positioning techniques, and
      the need for radiolucent operating-room tables. Although prospective studies have
      yet to be conducted, the ways in which the surgeon will benefit from the use of
      intraoperative three-dimensional imaging are apparent, but indications for
      combined three-dimensional C-arm navigated procedures at the hip and knee joint
      are still limited. Future directions may include the use of digital flat-panel
      detectors and even robotic-controlled C-arm motion.

PMID- 19182022
TI  - Section IV: Macromolecular imaging of cartilage.

PMID- 19182023
TI  - Toward imaging biomarkers for glycosaminoglycans.
AB  - Advances in the diagnosis and treatment of cartilage degeneration will be
      accelerated with the availability of validated biomarkers that reveal the
      features relevant to the health of cartilage. Using the delayed gadolinium
      enhanced magnetic resonance imaging of cartilage (dGEMRIC) technique for
      evaluating tissue glycosaminoglycan as a case study, I review the types of
      evidence needed to validate imaging (or other) biomarkers. In addition, I present
      discussions about face validity and technical validity and offer a review of
      emerging data that provide pathophysiologic validity. Examples of such data
      include evidence that glycosaminoglycan content is restored after an injury
      induced loss and evidence suggesting that dGEMRIC can indicate when it is too
      late for protective (load-modifying) surgery. These and other data suggest that
      new imaging biomarkers may indeed be able to provide a state-of-cartilage proxy
      that can be of use in the diagnosis and staging of disease.

PMID- 19182024
TI  - Section V: Knee degeneration.

PMID- 19182025
TI  - Tracking longitudinal changes in knee degeneration and repair.
AB  - The ability to track longitudinal changes in knee degeneration and repair is
      critical to understanding the natural history of joint disease as well as the
      impact of therapeutics and lifestyle interventions. Traditionally, longitudinal
      changes in the knee have been monitored with radiography, which focuses on
      relatively late disease progression. The ability of magnetic resonance imaging to
      monitor tissue composition may enable monitoring of early degeneration as well as
      repair. Most studies thus far have focused on cartilage, although there is
      increasing recognition of the need for molecular imaging of bone, ligament, and
      meniscus. The three magnetic resonance imaging parameters that have been utilized
      up to this point in studies of cartilage in the knee are T2-weighted, T1rho
      weighted, and delayed gadolinium-enhanced magnetic resonance imaging of cartilage
      (dGEMRIC). Perhaps the main impact of these newer methods lies in their ability
      to demonstrate, in vivo, that native cartilage can repair or reverse apparent
      degenerative changes. This ability should alter the mind-set of clinical
      investigators and encourage them to shift the focus of their studies to early
      detection of degeneration and to interventions that reverse the damage before
      long-term effects become apparent. In fact, a number of clinical studies have
      demonstrated an improvement in the biochemical status of cartilage over time,
      including an increase in the dGEMRIC index with exercise intervention, after
      traumatic injury, and after surgical interventions. The ability of magnetic
      resonance imaging to visualize osteoarthritis as a regional and responsive
      (reversible) disease may lead to new paradigms for developing and applying
      lifestyle, medical, and surgical therapeutic interventions.

PMID- 19182026
TI  - Plain radiography and magnetic resonance imaging diagnostics in osteoarthritis:
      validated staging and scoring.
AB  - Osteoarthritis is the most common joint disorder worldwide, and it has an
      enormous socioeconomic impact both in the United States and throughout the world.
      Conventional radiography is the simplest and least expensive imaging method for
      assessing osteoarthritis of the knee. Radiography is able to directly visualize
      osseous features of osteoarthritis, including marginal osteophytes, subchondral
      sclerosis, and subchondral cysts, and it is used in clinical practice to confirm
      the diagnosis of osteoarthritis and to monitor progression of the disease.
      However, the assessment of joint-space width provides only an indirect estimate
      of cartilage thickness and meniscal integrity. Magnetic resonance imaging, with
      its unique ability to examine the joint as a whole organ, holds great promise
      with regard to the rapid advancement of knowledge about the disease and the
      evaluation of novel treatment approaches. Magnetic resonance imaging has been
      applied widely in quantitative morphometric cartilage assessment, and
      compositional measures have been introduced that evaluate chondral integrity. In
      addition, magnetic resonance imaging-based validated semiquantitative whole-organ
      scoring methods have been applied for cross-sectional and longitudinal joint
      evaluation. This review describes currently applied radiographic and magnetic
      resonance imaging staging and scoring methods for the assessment of
      osteoarthritis of the knee and focuses on the strengths and weaknesses of the two
      modalities with regard to their use in clinical trials and epidemiologic studies.

PMID- 19182027
TI  - Minimally invasive robotic-arm-guided unicompartmental knee arthroplasty.
AB  - Unicompartmental knee arthroplasty is an underused procedure in orthopaedic
      surgery due to its level of difficulty and the unpredictability of results, which
      can be related to component malalignment. New robotic arm technology has been
      developed to assist the surgeon in accurately and reproducibly preparing the
      femur and the tibia for a minimally invasive bone-sparing unicompartmental knee
      arthroplasty. This new procedure provides comprehensive three-dimensional
      planning of unicompartmental knee arthroplasty components, including soft-tissue
      balancing, followed by accurate resection of the femur and the tibia. This paper
      reviews this new technology.

PMID- 19182028
TI  - Unicompartmental knee arthroplasty with use of novel patient-specific resurfacing
      implants and personalized jigs.
AB  - This paper describes the surgical technique with a patient-specific resurfacing
      unicompartmental knee arthroplasty. The patient-specific implant is currently
      designed on the basis of data from preoperative computed tomography. The implant
      is provided with a set of patient-specific, disposable cutting jigs.
      Biomechanical and anatomic axes are factored into jigs from a scan obtained
      through the hip, knee, and ankle, effectively achieving pre-navigation of the cut
      planes without the need for a navigation system. The surgical technique is
      reduced to five simple, reproducible steps. After removing the articular
      cartilage, the knee is balanced to determine the correct amount of tibial
      resection; this is followed by femoral preparation, verification of balancing and
      tibial preparation, and trial and cementing of the implant. The introduction of
      personalized three-dimensional image-derived resurfacing implants, as well as
      personalized single-use instrumentation, has the potential to change the common
      surgical practice of unicompartmental knee arthroplasty. Patient-specific
      resurfacing implants enable a femoral bone-preserving approach and enhance
      cortical bone support on the tibia, overcoming critical design limitations of
      commercial off-the-shelf implants. Patient-specific resurfacing implants can
      restore normal anatomy, the position of the joint line, and normal joint
      function, with the potential to result in more normal knee kinematics.

PMID- 19182029
TI  - Section VI: Malalignment and ligamentous injury.

PMID- 19182030
TI  - Evaluation of knee stability with use of a robotic system.
AB  - In our research center, we have developed and utilized a novel robotic/universal
      force-moment sensor testing system to gain quantitative data on multiple-degree
      of-freedom kinematics of the knee simultaneously with data on the in situ forces
      in normal and repaired soft tissues. In particular, we have investigated the
      complex interaction of the anteromedial and posterolateral bundles of the
      anterior cruciate ligament as well as several key biomechanical variables in
      anterior cruciate ligament reconstruction, such as graft selection and femoral
      tunnel placement (both of which impact knee stability). For example, both the
      bone-patellar tendon-bone and quadrupled hamstrings tendon autografts restored
      anterior stability but were insufficient in gaining rotatory stability. In a
      follow-up study, we have shown that a more laterally placed graft was beneficial
      and could improve these outcomes. Such findings led to additional investigation
      in which the biomechanical advantages of double-bundle anterior cruciate ligament
      reconstruction were demonstrated. However, a more laterally placed autograft at
      the femoral insertion of the posterolateral bundle also worked well, especially
      when the knee was nearly at full extension (a position in which the anterior
      cruciate ligament is needed most). At present, we are moving forward by obtaining
      in vivo kinematics data and then repeating those kinematics exactly to obtain new
      data with use of the robotic/universal force-moment sensor testing system in
      order to gain further insight regarding the function of the anterior cruciate
      ligament and anterior cruciate ligament replacement grafts in vivo. In parallel,
      we are developing a mathematical model of the knee and validating the
      computational model with experimental data. The combined approach will yield new
      and relevant information, including the stress and strain distribution in the
      anterior cruciate ligament and anterior cruciate ligament grafts. This will
      facilitate a better understanding of the function of the anterior cruciate
      ligament and a scientifically based design of surgical procedures and
      postoperative rehabilitation protocols that will lead to better patient outcomes.

PMID- 19182031
TI  - Alignment and osteoarthritis of the knee.
AB  - Osteoarthritis is widely believed to result from local mechanical factors acting
      within the context of systemic susceptibility. Previous studies have demonstrated
      that malalignment is a potent predictor of disease progression in patients with
      osteoarthritis of the knee. Malalignment also mediates the effects of other risk
      factors, including obesity, quadriceps strength, laxity, and stage of disease.
      Recent studies have had conflicting results regarding whether malalignment
      increases the risk of incident tibiofemoral osteoarthritis. While the evidence is
      conflicting, malalignment appears to play a smaller role in incident disease.
      Certain local factors within the joint, such as tibiofemoral congruence,
      integrity of the anterior cruciate ligament, and meniscal degeneration and
      position, appear to play a role in determining alignment. It is also apparent
      that malalignment changes with disease progression and is itself possibly
      influenced by structural changes within the joint.

PMID- 19182032
TI  - Reliability of image-free navigation to monitor lower-limb alignment.
AB  - Proper alignment of the mechanical axis of the lower limb is the principal goal
      of a high tibial osteotomy. A well-accepted and relevant technical specification
      is the coronal plane lower-limb alignment. Target values for coronal plane
      alignment after high tibial osteotomy include 2 degrees of overcorrection, while
      tolerances for this specification have been established as 2 degrees to 4
      degrees. However, the role of axial plane and sagittal plane realignment after
      high tibial osteotomy is poorly understood; consequently, targets and tolerance
      for this technical specification remain undefined. This article reviews the
      literature concerning the reliability and precision of navigation in monitoring
      the clinically relevant specification of lower-limb alignment in high tibial
      osteotomy. We conclude that image-free navigation registration may be clinically
      useful for intraoperative monitoring of the coronal plane only. Only fair and
      poor results for the axial and sagittal planes can be obtained by image-free
      navigation systems. In the future, combined image-based data, such as those from
      radiographs, magnetic resonance imaging, and gait analysis, may be used to help
      to improve the accuracy and reproducibility of quantitative intraoperative
      monitoring of lower-limb alignment.

PMID- 19182033
TI  - Gait mechanics influence healthy cartilage morphology and osteoarthritis of the
      knee.
AB  - The response of healthy and diseased cartilage of the knee to the mechanics of
      walking is examined, with the goal of providing insight into the relationship
      between the kinematics and kinetics of the knee during walking and the
      maintenance of cartilage health. The combination of information from three
      dimensional thickness models of cartilage derived from magnetic resonance imaging
      and the analysis of the interaction between load at the knee and kinematic
      changes during walking associated with loss of the anterior cruciate ligament
      demonstrated the importance of considering walking mechanics as an important
      factor in the initiation and progression of osteoarthritis. In particular, this
      material suggests that knee cartilage becomes conditioned to loading and to the
      large number of repetitive cycles of loading that occur during walking and that
      healthy cartilage homeostasis is maintained as long as there are no changes to
      the normal patterns of locomotion, the structure of the knee joint, or cartilage
      biology. Thus, there is the potential for a degenerative pathway to be initiated
      when a condition such as anterior cruciate ligament injury causes the repetitive
      loading during walking to shift to a new location. The sensitivity of cartilage
      to the kinematic changes is illustrated with the anterior cruciate ligament
      deficient knee and the regional variations in cartilage morphology. The material
      presented here supports the conclusion that individual variations in the range of
      loading and kinematics at the knee during walking can have a profound influence
      on the initiation and progression of osteoarthritis of the knee.

PMID- 19182034
TI  - Navigated long-bone fracture reduction.
AB  - The first computer-assisted orthopaedic trauma procedures were limited to
      navigated drill-guide applications, in which the computer was used to predict the
      trajectory of the drill guide relative to stored radiographic images. By 2003,
      software for fracture reduction was commercially available. The ability to
      perform a minimally invasive fracture reduction with the aid of stored images,
      combined with navigated insertion of internal fixation, has long been considered
      the highest achievement in image-guided fracture surgery. It is now possible to
      apply computer-assisted techniques to all fractures that have traditionally been
      treated with the aid of intraoperative fluoroscopic control. Less-invasive
      fixation of long-bone fractures is often complicated by malrotation or shortening
      of the injured extremity, sometimes requiring reoperation. Recent developments in
      computer-assisted surgery now allow the orthopaedic surgeon to precisely match
      the anatomy of the injured extremity to that of the uninjured limb with respect
      to length and rotational alignment. This is particularly important in comminuted
      fractures, for which there are no anatomic clues to guide accurate reduction, and
      in the correction of malreduced fractures. Although computer-assisted technology
      is now readily available, it has not yet found widespread acceptance in the
      orthopaedic trauma community. New software workflows (i.e., the step-by-step
      progression through various screens in the software program during a computer
      guided procedure) specific to individual procedures and implants may hasten
      adoption of these techniques.

PMID- 19182036
TI  - The pivot-shift phenomenon during computer-assisted anterior cruciate ligament
      reconstruction.
AB  - Anterior cruciate ligament reconstruction was one of the first procedures in
      which computer-assisted techniques were used in orthopaedic surgery. However, the
      use of navigation for tunnel placement in anterior cruciate ligament surgery
      remains problematic, as the optimal position for placement of the tunnels is
      debatable. The technical specification of tunnel position is clinically relevant,
      but the targets and tolerances for this technical specification are poorly
      understood. The inability to reliably quantify knee kinematics and stability
      before, during, or after anterior cruciate ligament reconstruction remains a
      problem. A navigated examination to assess knee stability could potentially close
      the computer-assisted surgery treatment loop by providing quantitative feedback
      about various reconstruction techniques. Recent iterations of navigated
      examinations for the assessment of stability include even complex pathologic
      movements, such as those detected with the pivot-shift examination. In this
      paper, we review conventional stability measurements of the knee and compare them
      with navigated techniques, with a focus on the navigated pivot-shift examination.
      In summary, direct intraoperative measurements and quantifications of knee
      stability, including the pivot-shift phenomenon, are now possible with the use of
      navigation. Consequently, more reproducible and clinically meaningful
      quantification of the pivot-shift phenomenon may allow for more accurate
      evaluation of various anterior cruciate ligament reconstruction techniques in the
      future.

PMID- 19182035
TI  - Evaluation of kinematics of anterior cruciate ligament-deficient knees with use
      of advanced imaging techniques, three-dimensional modeling techniques, and
      robotics.
AB  - Measuring knee biomechanics in six degrees of freedom with acceptable accuracy
      has been proven to be technically challenging. At our bioengineering laboratory,
      we have employed both an in vitro robotic testing system and an in vivo combined
      dual fluoroscopic and magnetic resonance imaging technique to analyze the impact
      of anterior cruciate ligament rupture on the knee joint. When measuring the
      tibiofemoral kinematics of nine cadavers with the robotic testing system, we
      found that anterior cruciate ligament deficiency not only altered anterior
      translation and axial rotation of the tibia, but it also increased the medial
      translation of the tibia as well. The in vivo dual fluoroscopic imaging analysis
      of tibiofemoral kinematics in ten anterior cruciate ligament-deficient patients
      revealed analogous findings: an increased medial translation of the tibia of
      approximately 1 mm between 15 degrees and 90 degrees of flexion was found in
      anterior cruciate ligament-deficient knees, in addition to an increased anterior
      translation (approximately 3 mm) and internal rotation (approximately 2 degrees)
      of the tibia at low flexion angles. In a subsequent study of tibiofemoral
      cartilage contact, we found that the cartilage contact points shifted posteriorly
      -as was expected on the basis of the increased anterior tibial translation--as
      well as laterally on the surface of the tibial plateau. The data demonstrate how
      rupture of the anterior cruciate ligament initiates a cascade of events that
      eventually results in abnormal tibiofemoral cartilage contact in both the
      anteroposterior and mediolateral directions. If the restoration of normal knee
      homeostasis is the ultimate goal of ligament reconstruction, the normal function
      of the anterior cruciate ligament should be restored as closely as possible in
      all degrees of freedom.

PMID- 19182037
TI  - Section VII: Chondral lesions.

PMID- 19182038
TI  - Current and novel approaches to treating chondral lesions.
AB  - Total joint arthroplasty remains the most effective treatment to relieve pain and
      restore function in damaged and diseased joints; however, less invasive, more
      functional solutions are necessary for young, active patients who have chondral
      defects and are at the early stages of disease. Unfortunately, attempts at
      providing such a method have provided variable and often unsatisfactory outcomes.
      Unicondylar knee replacement, for example, is associated with a markedly higher
      rate of revision when compared with total knee arthroplasty, and there is a
      distinct probability of disease progression in the remaining joint compartments.
      Small metallic caps intended for filling the cartilage defects are commercially
      available, but the clinical follow-up of patients who have undergone this
      treatment is short. Although not yet in clinical use, synthetic polymeric implant
      scaffolds, with and without cell-seeding, are also under development. The
      biomechanical requirements for treating chondral lesions, like those of total
      knee arthroplasty, are wear and fixation. A lesion-filling implant must carry
      large joint loads without damaging the opposing tissue. Integration with
      surrounding cartilage and subchondral bone would enhance load-sharing and load
      transfer. The challenge of meeting these requirements is difficult, but new forms
      of computational models and in vitro tests can aid in establishing performance
      and in rapidly screening possible solutions.

PMID- 19182039
TI  - Magnetic resonance imaging assessment of chondral lesions and repair.
AB  - Standardized, validated magnetic resonance imaging sequences that are sensitive
      for articular cartilage are available for clinical use in magnetic resonance
      imaging units. Whereas two-dimensional sequences are helpful in the assessment of
      repair morphology, three-dimensional sequences with isotropic voxels measure
      cartilage volumes and provide an accurate assessment of fill following repair.
      Protocols should be modified so that sequences are not limited by
      instrumentation. The addition of quantitative magnetic resonance imaging
      techniques provides an objective assessment of repair-tissue biochemistry as well
      as of the tissue at the peripheral integration with the host hyaline cartilage.

PMID- 19182040
TI  - Use of imaging biomarkers for regulatory studies.
AB  - Imaging often plays an important role in pivotal clinical trials of drugs or
      devices that have been submitted for approval to regulatory agencies that grant
      approval for the marketing and sale of these products on the basis of
      documentation of their safety and efficacy. Imaging biomarkers can help
      substantiate either or both of these characteristics. This article focuses on how
      to successfully incorporate imaging biomarkers into clinical trials through a
      process of careful planning and diligent execution. Planning starts with posing
      and then answering a number of questions that pertain to the product under study.
      What will the claimed benefit of the product be? Is there a current standard of
      care that involves imaging, and will that standard of care help in the
      documentation of safety and efficacy? Are there relevant novel imaging
      biomarkers? Are there any relevant guidance documents issued by the regulatory
      agencies? After imaging biomarkers are identified, their role and benefit must be
      understood. Will they help diagnose subjects? Will they stratify subjects for
      enrollment? Will they identify those who are more likely to benefit? Will they
      help document progression of disease and effectiveness of intervention? Execution
      must occur in close collaboration with regulatory agencies and with the
      involvement of imaging experts and imaging core laboratories to ensure attention
      to key components: imaging charter, investigator training and certification, 21
      CFR Part 11 (Part 11 of Title 21 of the U.S. Code of Federal Regulations)
      compliant data management, real-time incoming image quality control for
      eligibility reads and investigator feedback, and centralized image analysis for
      safety and efficacy by certified readers.

PMID- 19182041
TI  - Section VIII: Novel approaches to imaging and tracking of hip topology.

PMID- 19182042
TI  - Imaging of femoroacetabular impingement.
AB  - Femoroacetabular impingement is a relatively recently described cause of hip pain
      that involves degenerative change in the hips of younger patients (less than
      thirty-five years old) as a result of predisposing pathoanatomy. The two types of
      impingement, cam and pincer, often occur together and overlap to varying degrees.
      The diagnostic workup begins with radiography, but magnetic resonance imaging and
      magnetic resonance arthrography provide more accurate imaging that characterizes
      not only the pathoanatomy but also other associated findings, including labral
      tears and cartilage damage.

PMID- 19182043
TI  - The combined use of simulation and navigation to demonstrate hip kinematics.
AB  - Computer navigation of total hip arthroplasty and computer simulation of hip
      motions based on collision detection were both introduced more than ten years
      ago. Neither of these promising technologies has achieved its full potential to
      improve patient outcomes. Combining these two technologies allows the individual
      strengths of each to more easily demonstrate hip kinematics in a clinically
      useful way. All normal and pathologic combined hip motions must be clearly and
      accurately reported to fully evaluate the kinematics involved in total hip
      arthroplasty, femoroacetabular impingement syndrome, and other hip disorders. The
      use of three-dimensional data graphs allows for a rapid and thorough evaluation
      of the very large data sets that are required for the purpose of making a
      complete report of all combined hip motions. Data can be obtained from
      simulations made with use of high-resolution computed tomographic scans and
      computer-aided implant-design files or from clinically obtained motion analysis
      on fresh cadavers or normal subjects. The use of these methods and graphics
      allows for the thorough evaluation of the geometries of current implant designs
      and will help improve future implant designs. The pathologic structures in hips
      with femoroacetabular impingement can be modeled in three dimensions, and
      surgical treatment plans can be developed to provide impingement-free normal hip
      motion without excessive osseous resection. The combination of these technologies
      provides hope for the improved surgical placement of total hip implants by
      providing the basis for a kinematic, impingement-based total hip navigation
      system.

PMID- 19182044
TI  - Role of navigation in total hip arthroplasty.
AB  - Current uses of computed tomography-based and imageless navigation systems for
      total hip arthroplasty include proper placement of the acetabular component,
      measurement of limb-length changes, enablement of minimally invasive surgery, and
      proper placement of components for hip resurfacing procedures. This article
      provides an overview of the rationale for computer-assisted surgery in total hip
      arthroplasty and hip resurfacing. The experience of the senior author (M.L.S.)
      with computer-assisted surgery for hip arthroplasty has demonstrated improved
      position of the acetabular component as compared with the position attainable
      with use of mechanical instruments, maintenance of appropriate position of the
      acetabular component during minimally invasive surgery, and appropriate
      positioning of the femoral and acetabular components during the learning curve
      for hip resurfacing procedures.

PMID- 19182045
TI  - Directions for future research.

PMID- 19182046
TI  - A descriptive study of educational outreach to promote use of quality improvement
      tools in primary care private practice.
AB  - The objective of this study was to describe the experience of a Quality
      Improvement Organization (QIO) providing educational outreach to promote use of
      quality improvement (QI) tools in primary care private practice. Two QIO outreach
      workers conducted visits with physicians and targeted staff. Data were analyzed
      on physician demographics, visits, and use of QI tools using standard
      quantitative and qualitative methods. QIO staff frequently encountered difficulty
      in accessing physicians and administrative staff and reported many barriers to
      QI. Despite these challenges, outreach visits were associated with adoption of QI
      tools, and certain physician characteristics were associated with greater numbers
      of outreach visits and tools adopted. QIOs and other external parties who seek to
      improve quality of care in private practice primary care physician offices face
      challenges in gaining access to physicians and administrative personnel.
      Additional study is needed to better understand associations between physician
      characteristics, educational outreach visits, and adoption of QI tools.

PMID- 19182047
TI  - Effects of practice, visual loss, limb amputation, and disuse on motor imagery
      vividness.
AB  - BACKGROUND: The ability to generate vivid images of movements is variable across
      individuals and likely influenced by sensorimotor inputs. OBJECTIVES: The authors
      examined (1) the vividness of motor imagery in dancers and in persons with late
      blindness, with amputation or an immobilization of one lower limb; (2) the
      effects of prosthesis use on motor imagery; and (3) the temporal characteristics
      of motor imagery. METHODS: Eleven dancers, 10 persons with late blindness, 14
      with amputation, 6 with immobilization, and 2 groups of age-matched healthy
      individuals (27 in control group A; 35 in control group B) participated. The
      Kinesthetic and Visual Imagery Questionnaire served to assess motor imagery
      vividness. Temporal characteristics were assessed with mental chronometry.
      RESULTS: The late blindness group and dance group displayed higher imagery scores
      than respective control groups. In the amputation and immobilization groups,
      imagery scores were lower on the affected side than the intact side and
      specifically for imagined foot movements. Imagery scores of the affected limb
      positively correlated with the time since walking with prosthesis. Movement times
      during imagination and execution (amputation and immobilization) were longer on
      the affected side than the intact side, but the temporal congruence between real
      and imagined movement times was similar to that in the control group.
      CONCLUSIONS: The mental representation of actions is highly modulated by imagery
      practice and motor activities. The ability to generate vivid images of movements
      can be specifically weakened by limb loss or disuse, but lack of movement does
      not affect the temporal characteristics of motor imagery.

PMID- 19182048
TI  - Partners in health? A systematic review of the impact of organizational
      partnerships on public health outcomes in England between 1997 and 2008.
AB  - OBJECTIVE: To systematically review the available evidence on the impact of
      organizational partnerships on public health outcomes (health improvement and/or
      a reduction in health inequalities) in England between 1997 and 2008. DESIGN:
      Systematic review of quantitative (longitudinal before and after) and qualitative
      studies (1997-2008) reporting on the health (and health inequalities) effects of
      public health partnerships in England. DATA SOURCES: Eighteen electronic
      databases (medical, social science and economic), websites, bibliographies and
      expert contacts. RESULTS: Only 15 studies, relating to six different
      interventions, met the review criteria and most of these studies were not
      designed specifically to assess the impact of partnership working on public
      health outcomes. Of the studies reviewed, only four included a quantitative
      element and they produced a mixed picture in terms of the impacts of partnership
      working. Qualitative studies suggested that some partnerships increased the
      profile of health inequalities on local policy agendas. Both the design of
      partnership interventions and of the studies evaluating them meant it was
      difficult to assess the extent to which identifiable successes and failures were
      attributable to partnership working. CONCLUSION: This systematic review suggests
      that there is not yet any clear evidence of the effects of public health
      partnerships on health outcomes. More appropriately designed and timed studies
      are required to establish whether, and how, partnerships are effective.

PMID- 19182049
TI  - Varieties of patriarchy and violence against women: resurrecting "patriarchy" as
      a theoretical tool.
AB  - Feminist scholars have produced abundant writings on violence against women, yet
      theory development has stagnated. The effort to construct a theory of patriarchy
      to explain violence against women was derailed by criticism. In this article, the
      author addresses some of these criticisms, uncovers the explanatory strengths of
      this concept, and lays some foundations for a more fully developed theory of
      violence against women. The concept of patriarchy holds promise for theorizing
      violence against women because it keeps the theoretical focus on dominance,
      gender, and power. It also anchors the problem of violence against women in
      social conditions, rather than individual attributes.

PMID- 19182050
TI  - Purulent vaginal and cervical discharge in the diagnosis of pelvic inflammatory
      disease.
AB  - In this structured review, we evaluated purulent vaginal and cervical discharge
      as diagnostic tests for pelvic inflammatory disease (PID). Using a pretest
      probability of PID (diagnosed clinically) of 50%, we used the odds-likelihood
      formulation of Bayes' theorem to calculate post-test probabilities of PID (proven
      by laparoscopy or endometrial biopsy). If abnormal discharge was present, the
      post-test probabilities of PID ranged from 50% to 73%, with a mean value of 57%.
      If abnormal discharge was absent, the post-test probabilities ranged from 24% to
      52%, with a mean value of 39%. Therefore, the presence or absence of excess white
      blood cells in vaginal or cervical discharge was not particularly helpful in
      confirming or excluding PID in patients in whom the diagnosis was suspected from
      the clinical examination.

PMID- 19182051
TI  - 2008 European Guideline on HIV testing.
AB  - Testing for HIV is one of the cornerstones in the combat against HIV infection.
      The 2008 European Guideline on HIV Testing provides advice on testing for HIV
      infection in individuals aged 16 years and older who have sought evaluation and
      treatment at sexually transmitted infection services for dermatovenereology
      clinics across Europe. Its aim is to provide practical guidance to clinicians in
      these settings who undertake HIV testing and suggest appropriate standards for
      the audit of service provision.

PMID- 19182052
TI  - Autopsies in HIV: still identifying missed diagnoses.
AB  - This study reviews the deaths and autopsies carried out over 23 years, 1983-2005,
      in a British Infection Unit in HIV patients. Of 115 HIV patients known to have
      died, we obtained data on 93%. Of this 80% were male, median age 38 (25-68)
      years; 83% were Caucasian; 12% Black African. Major risk factors were men who
      have sex with men, 52%; heterosexual in Africa, 17%; and injecting drug use, 8%.
      The commonest diagnosis pre- and post-autopsy diagnosis was pneumonia. Changes in
      diagnoses in the 38% who underwent autopsy were high (we requested autopsy in
      50%). Primary diagnosis changed in 70%, and 36% of all opportunistic infections
      were missed. This included six of nine cytomegalovirus, all tuberculosis and 75%
      of Kaposi's sarcoma. Lymphoma was overdiagnosed. Thus, despite excellent
      resources, the majority of primary diagnoses were wrong, suggesting inadequacy of
      current diagnostics. To improve these and improve both epidemiological data and
      future management autopsy should be considered for all deaths.

PMID- 19182053
TI  - Behaviourally bisexual men as a bridge population for HIV and sexually
      transmitted infections? Evidence from a national probability survey.
AB  - We consider the potential of behaviourally bisexual men (BBM) as a bridge
      population in sexually transmitted infection (STI)/HIV transmission by comparing
      sexual risk behaviours, attitudes and sexual health outcomes of BBM (defined as
      men who reported sex with men and women), with men who reported (i) exclusively
      male partners (MEMP) and (ii) exclusively female partners (MEFP), using a
      probability survey of the British general population aged 16-44 years, conducted
      between 1999 and 2001 (n = 5168 men). About 1.3% of men who reported sex in the
      past five years were BBM (44.1% of all men reporting male partners); 29.0% of BBM
      were married/cohabiting with women. Median partner numbers in this timeframe were
      seven among BBM, two among MEFP and 10 among MEMP. Similar proportions of BBM and
      MEMP reported STI diagnosis/es in the past five years, yet BBM were less likely
      than MEMP to report HIV-testing (odds ratio adjusted for sociodemographics:
      0.31). BBM are thus mid-way between MEFP and MEMP in their sexual risk behaviour,
      but are similar to MEMP in reporting STI diagnosis/es. These data have
      implications for health promotion and partner notification, as BBM are unlikely
      to be appropriately targeted by safe-sex messages aimed at men identifying as
      gay.

PMID- 19182054
TI  - Sexual risk behaviour of the first cohort undergoing screening for enrollment
      into Phase I/II HIV vaccine trials in South Africa.
AB  - We assessed risk behaviour in a heterosexual cohort undergoing prescreening for
      the first Phase I/II HIV vaccine trials in Soweto. We developed a survey and
      collected self-reported data from HIV-negative potential volunteers. Of 488
      participants, most were single and approximately half were from households with
      incomes below the poverty level. Males reported higher rates of heavy alcohol use
      (P < 0.001), marijuana use (P < 0.001) and other recreational drug use (P <
      0.01). Males reported more sex partners than females in the previous six months
      (P < 0.001), as well as more casual/anonymous partners (P < 0.001) and one-night
      stands (P < 0.001). Multivariate analyses revealed substance use and male gender
      predicted higher risk behaviours, including <100% condom use with known/suspected
      HIV-positive partners, having casual/anonymous partners and having more than two
      partners. For this population, male volunteers may need increased risk-reduction
      counselling during Phase I/II trials and additional recruitment methods may be
      necessary to identify high-risk female volunteers for Phase III efficacy trials.

PMID- 19182055
TI  - Knowledge of human papillomavirus and attitudes to vaccination among Swedish high
      school students.
AB  - The aim of the study was to investigate knowledge of and attitudes to sexually
      transmitted infection (STI) and STI prevention with special focus on human
      papillomavirus (HPV) and the new vaccine against HPV, among 16-year-old high
      school students in a Swedish context. A study-specific questionnaire was
      distributed to 572 first year high school students from five different high
      schools in a medium-sized town in Sweden. The students lacked knowledge of HPV
      and its association with cervical cancer. Similarly, their knowledge of the new
      vaccine was limited. Their attitude to condom use when having sex with a new
      partner was positive, but decreased if oral contraceptives were used and if they
      were vaccinated against an STI. The main source of information was the school,
      followed by youth clinics and the media. The results highlight the clinical
      importance for school nurses and personnel at youth clinics to inform adolescents
      about HPV and its association with cancer.

PMID- 19182056
TI  - Can bacterial vaginosis help to find sexually transmitted diseases, especially
      chlamydial cervicitis?
AB  - This study was undertaken to establish reliable factors in order to identify
      chlamydial cervicitis among suspicious patients. Between January and December
      2007, 406 patients who were suspected to have cervicitis due to clinical
      symptoms, were tested with polymerase chain reaction (PCR) for Chlamydia
      trachomatis (CT), vaginal pH and Nugent score (NS) in our University hospital and
      related clinics. During the same period, 67 patients who were diagnosed as having
      other sexually transmitted diseases (Neisseria gonorrhoeae (NG), Trichomonas
      vaginalis, Condyloma acuminatum and genital herpes) were also made to participate
      in this study. Eighty-nine women (22%) were positive for CT PCR. Bacterial
      vaginosis (BV)-positive women were tested positive for CT PCR (75/288),
      significantly higher than those without BV (6/66, P = 0.01). In addition, under
      20-years old women were positive for CT PCR (24/57), significantly higher than
      those who were over 30 years old (16/113, P = 0.001). The proportion of patients
      with high NS (>7) in CT, NG and T. vaginalis cases were 75/89 (84.3%), 22/27
      (81.5%) and 11/14 (78.6%), respectively. Whereas the high NS of the C. acuminatum
      and genital herpes groups were recorded at 7/14 (50%) and 4/12 (33.3%),
      respectively. Younger women with BV could be at a higher risk for STDs,
      especially for CT cervicitis.

PMID- 19182057
TI  - Herpes simplex virus-2 infection in male rural migrants in Shanghai, China.
AB  - The overall herpes simplex virus (HSV)-2 seroprevalence was 5.5% among male rural
      migrants working in construction sites, markets and factories, 5.4% among those
      reporting having had sexual intercourse and 5.8% among those reporting no sexual
      intercourse. Multiple logistic regression analyses indicate that migrants having
      higher income were more likely to have HSV-2 infection. None of the HSV-2
      positives realized their infection status. Future sexually transmitted disease
      (STD) intervention programmes should target migrants with higher income and
      migrant market vendors and should not exclude those who self-report no STDs or no
      history of sexual intercourse.

PMID- 19182058
TI  - Burden of syphilis infections in Shenzhen, China: a preliminary estimation.
AB  - Information on the prevalence and incidence of sexually transmitted infections is
      important for developing prevention and control strategies and allocating human
      and financial resources. However, there are no available estimates of such
      information for many areas in China. In this study, we used the existing data to
      make a preliminary estimation of syphilis infections in Shenzhen city, in south
      eastern China. Data on prevalence rates of syphilis infections among different
      populations were obtained from the local HIV/sexually transmitted disease second
      generation surveillance programme, and the sizes of different populations were
      estimated based on the most recently available figures. It was estimated that
      83,760 (range 77,490-90,020) people are currently infected with syphilis, giving
      a prevalence of 0.71-0.82% (0.76% on average) in Shenzhen. Around 18% of these
      syphilis infections occur among men who have sex with men and another 15.8% and
      8.7% occur among female sex workers and their clients, respectively. These
      estimates suggest that a combination of unprotected paid sex and sex between men
      may be sustaining the epidemic of syphilis in the study area. The preliminary
      estimates will assist the government in planning and improving its comprehensive
      intervention programmes for the future control and prevention of syphilis.

PMID- 19182059
TI  - Knowledge of HIV survival on skin-piercing instruments among young adults in
      Nyanza Province, Kenya.
AB  - In countries with generalized HIV epidemics, people may be exposed to blood-borne
      HIV at their home as well as during health care and cosmetic services. We asked
      young adults from the Luo and Kisii ethnic groups in Nyanza Province, Kenya, how
      long HIV survives in blood and how to clean skin-piercing instruments. Only 21%
      thought that HIV could survive more than an hour in dry conditions (although it
      can survive for days), and only 24% thought it could survive more than a week in
      wet conditions (although it can survive more than four weeks). The Kisii, with
      lower HIV prevalence, were more knowledgeable than the Luo about HIV survival.
      Survey participants reported that barbers and other service providers often
      cleaned instruments by wiping with alcohol or bleach, a practice which does not
      reliably inactivate HIV. People we interviewed, at risk from blood-borne HIV, did
      not know enough to protect themselves.

PMID- 19182060
TI  - Improvement of the patient flow in a large urban clinic with high HIV
      seroprevalence in Kampala, Uganda.
AB  - Antiretroviral treatment roll-out programmes in Africa often have difficulties to
      cope with the increasing number of clients. Based on the findings of a survey
      carried out in 2005 that showed long waiting times, innovative organizational
      changes (nurse visits and pharmacy-only refill visits) were introduced in our
      clinic. In August 2007, the survey was repeated to evaluate the impact of these
      changes. During both surveys we used the same standardized questionnaire. In
      2007, 400 patients visited the clinic on the study day compared to 250 in 2005.
      The median time spent at the clinic decreased from 157 minutes in 2005 (range 22
      426) to 124 minutes (15-314). All the waiting times for different services
      decreased except the time between the visit to the triage nurse and the doctors'
      visit. A similar methodology could be used by other health services to evaluate
      and compare different models of care.

PMID- 19182061
TI  - A quasi-experimental study on a community-based behaviour change programme among
      injecting drug users in Sichuan, China.
AB  - The objective of this study is to explore an effective model of comprehensive
      intervention on HIV/AIDS among injecting drug users (IDUs) in communities located
      in urban areas and to evaluate its feasibility in Sichuan Province, China. A
      quasi-experimental study was designed so that various intervention measures were
      conducted in the intervention city but not in the control city. A Behaviour
      Surveillance Survey was introduced to evaluate intervention exposure and the
      effect of behaviour change. In the intervention city, services received by IDUs
      increased over time (P < 0.001). Awareness of HIV increased from 34.2% in 2003 to
      58.3% in 2004, and to 67.4% in 2005 (P < 0.001). The proportion of IDUs surveyed
      who shared a needle the last time they injected drugs decreased from 17.1% in
      2003 to 7.0% in 2005, and in terms of the past month from 42.4% in 2003 to 18.4%
      in 2005 (P < 0.001). Data from a multivariate logistic regression analysis showed
      that comprehensive intervention was a protective factor for behaviour change
      (odds ratio [OR] =0.561; 95% confidence interval [CI], 0.424-0.741). A well
      designed and organized comprehensive intervention programme will effectively
      change the high-risk behaviour among IDUs in these communities. A more
      comprehensive, expanded and integrated response is needed when conducting an
      HIV/AIDS prevention programme.

PMID- 19182062
TI  - Summary of proceedings of the IUSTI Global Challenges Symposium (ISSTDR 2007/10th
      IUSTI World Congress).

PMID- 19182063
TI  - Risk profile of walk-in triage compared with an appointment-based phone-triage
      evening clinic.
AB  - The aim of this study is to compare risk factors in new clients attending the
      walk-in triage-based day clinic (WITS) to those attending a telephone-triage
      appointment-based evening clinic of a sexual health service. The method involves
      an audit of computerized medical records of new clients attending between July
      2002 and December 2007. There were 37,833 new clients of which 37,223 (98.4%)
      attended WITS and 610 (1.6%) attended the evening clinic. WITS clients were
      significantly older (31% vs. 30%, P < 0.041), more likely to be male (58% vs.
      43%, P < 0.001), sex workers (6% vs. 3%, P < 0.001), not employed (34% vs. 10%, P
      < 0.001), diagnosed with gonorrhoea (1.7% vs. 0.7%, P < 0.041), herpes (4% vs.
      2%, P < 0.000), non-specific urethritis (6% vs. 2%, P < 0.000) and less likely
      asymptomatic (35.1% vs. 53.4%, P < 0.001). Men attending WITS had significantly
      more female partners in the 12 months (3.9 vs. 3.0, P < 0.001), but other risks
      were similar in both clinics. A telephone-triage appointment-based evening clinic
      is important for asymptomatic high-risk individuals.

PMID- 19182064
TI  - Long-term suppressive therapy for herpes simplex - an audit.
AB  - A retrospective analysis of patients, who have been on long-term suppressive
      therapy for recurrent episodes of herpes simplex (HSV) in a university hospital,
      was performed and the findings were documented and orchestrated into bar graphs.
      The study involved patients between the years 2000 and 2007, both inclusive. The
      results were compared with the British Association for Sexual Health and HIV
      guidelines. Eighty-two percent (57) had had the infection for at least 12 months
      at the start of therapy and 78.2% (54) had at least six recurrences per year
      before the start of treatment. Indeed, only four patients (5.8%) had a treatment
      interruption at 12 months or less; also only 11 patients (15.9%) had less than
      six outbreaks per year at the start of treatment. The former is not in-line and
      the latter is in-line with the guidelines.

PMID- 19182065
TI  - Kikuchi-Fujimoto syndrome presenting to a sexual health clinic.
AB  - We report on a 37-year-old woman who presented with a six-week history of
      bilateral, tender lymph nodes in her groin. An initial biopsy was done with the
      histology 'suggestive of lymphogranuloma venereum (LGV)'. She had not had sexual
      intercourse for over two years and had no symptoms or signs of note to report.
      Examination revealed large, smooth tender lymph nodes above the inguinal ligament
      bilaterally with no other areas of lymphadenopathy. Due to a possible diagnosis
      of LGV, three weeks of doxycycline was given. A further review of the histology
      slides revealed 'subacute necrotizing lymphadenitis' highly suggestive of Kikuchi
      Fujimoto syndrome of unknown cause, which is usually self-limiting. Subsequent
      follow-up of the patient revealed a reduction in the lymph nodes size with little
      tenderness.

PMID- 19182066
TI  - Texting appointment reminders reduces 'Did not Attend' rates, is popular with
      patients and is cost-effective.

PMID- 19182067
TI  - Dual infection with Neisseria gonorrhoeae and Chlamydia trachomatis.

PMID- 19182068
TI  - Confirmed new HIV diagnoses in men who have sex with men after episodes of rectal
      gonorrhoea.

PMID- 19182069
TI  - Challenges in the search for drugs to treat central nervous system disorders.
AB  - The history of drug discovery spans approximately 200,000 years. For much of this
      time, the identification of therapeutic agents was empirical, with the shift to a
      more hypothesis-driven approach occurring in the late 19th century. Since then,
      the objective has changed from identifying an active drug and its mechanism of
      action to determining therapeutic potential only after identifying drug-like
      compounds that interact with a target site. Although the emphasis on target
      identification, or "targephilia," has yielded novel drugs, overall it appears to
      have slowed the drug discovery process, especially for compounds used in treating
      central nervous system (CNS) disorders. This is because the "targephilic"
      approach requires a good understanding of target physiology and its integration
      with the target organ, with a hierarchical integration from in vitro cellular and
      functional tissue studies to animal models that reasonably predict human
      responses. Because the majority of CNS drugs were discovered empirically, drug
      discovery in this area appears less amenable to target-based approaches than it
      seems for other types of therapeutics. Improving the success rate in CNS drug
      discovery requires a more pharmacometric-based approach, with a renewed emphasis
      on defining basic CNS function in intact animals and a more systematic in vivo
      screening of novel structures. Efforts must also be directed toward defining the
      sites of action of existing CNS drugs to aid in the design of second-generation
      agents with improved efficacy and safety.

PMID- 19182070
TI  - Preclinical evaluation of melanin-concentrating hormone receptor 1 antagonism for
      the treatment of obesity and depression.
AB  - The mammalian neuropeptide, melanin-concentrating hormone, interacts with two G
      protein-coupled receptors, melanin-concentrating hormone receptor (MCHR) 1 and
      MCHR2; however, only MCHR1 is expressed in rats and mice. In the present study,
      we evaluated MCHR1 antagonism in preclinical models believed to be predictive of
      antiobesity and antidepressant activity. Central activity of the selective MCHR1
      antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl
      ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one], was evaluated using ex vivo
      binding with autoradiography. Effective doses of GW803430 (1 and 3 mg/kg p.o.)
      were correlated with antiobesity activity in a 14-day study of diet-induced obese
      rats. GW803430 was evaluated subsequently for antidepressant-like effects in mice
      and rats. Acute and subchronic administration reduced immobility time in the
      mouse forced-swim test at doses of 3 (acute) and 3 and 10 (chronic) mg/kg p.o.,
      an effect that was absent in MCHR1(-/-) mice. Combined subeffective doses of
      GW803430 (0.3 and 1 mg/kg p.o.) and imipramine (5 mg/kg) produced a robust
      antidepressant-like response. The compound was also active in the tail suspension
      test at a dose of 10 mg/kg p.o. GW803430 (30 mg/kg p.o.) significantly reduced
      submissive behaviors at weeks 2 and 3, a model of submissive behavior that may
      predict antidepressant onset. GW803430 decreased marble burying in mice at doses
      of 3, 10, and 30 mg/kg p.o., an assay that detects anxiolytic-like effects. Thus,
      GW803430 produces robust antiobesity and antidepressant-like effects in rats and
      mice at doses that compete for central MCHR1 in vivo. As such, MCHR1 should be
      considered as a promising target for future drug discovery efforts.

PMID- 19182071
TI  - Motor imagery after subcortical stroke: a functional magnetic resonance imaging
      study.
AB  - BACKGROUND AND PURPOSE: In recovered subcortical stroke, the pattern of motor
      network activation during motor execution can appear normal or not, depending on
      the task. Whether this applies to other aspects of motor function is unknown. We
      used functional MRI to assess motor imagery (MI), a promising new approach to
      improve motor function after stroke, and contrasted it to motor execution.
      METHODS: Twenty well-recovered patients with hemiparetic subcortical stroke (14
      males; mean age, 66.5 years) and 17 aged-matched control subjects were studied.
      Extensive behavioral screening excluded 8 patients and 4 control subjects due to
      impaired MI abilities. Subjects performed MI and motor execution of a paced
      finger-thumb opposition sequence using a functional MRI paradigm that monitored
      compliance. Activation within the primary motor cortex (BA4a and 4p), dorsal
      premotor, and supplementary motor areas was examined. RESULTS: The pattern of
      activation during affected-hand motor execution was not different from control
      subjects. Affected-hand MI activation was also largely similar to control
      subjects, including involvement of BA4, but with important differences: (1)
      unlike control subjects and the nonaffected hand, activation in BA4a and dorsal
      premotor was not lower during MI as compared with motor execution; (2) the
      hemispheric balance of BA4p activation was significantly less lateralized than
      control subjects; and (3) ipsilesional BA4p activation positively correlated with
      motor performance. CONCLUSIONS: In well-recovered subcortical stroke, the motor
      system, including ipsilesional BA4, is activated during MI despite the lesion.
      It, however, remains disorganized in proportion to residual motor impairment.
      Thus, components of movement upstream from execution appear differentially
      affected after stroke and could be targeted by rehabilitation in more severely
      affected patients.

PMID- 19182072
TI  - Chronic kidney disease and clinical outcome in patients with acute stroke.
AB  - BACKGROUND AND PURPOSE: Chronic kidney disease (CKD) is increasingly recognized
      as an independent risk factor for cardiovascular disease and stroke. Our aim was
      to examine the association between estimated glomerular filtration rate (GFR) and
      stroke outcome and to assess whether CKD and its severity affect stroke outcome
      in a large cohort of unselected patients with acute stroke. METHODS: We examined
      the association between baseline estimated GFR and CKD and 1-year outcomes in 821
      consecutive patients with acute stroke (ischemic or hemorrhagic). GFR was
      estimated by 2 methods: the Modification of Diet in Renal Disease and the Mayo
      Clinic quadratic equation. An estimated GFR rate <or=60 mL/min/1.73 m(2) defined
      CKD. RESULTS: Odds ratios (95% CI) for death across levels of estimated GFR based
      on both equations were estimated. CKD was present in 36% (n=291) of patients
      based on the Modification of Diet in Renal Disease equation and 18% (n=147) based
      on the Mayo Clinic equation. The adjusted ORs for mortality after 1-year based on
      the Modification of Diet in Renal Disease equation were 0.7 (95% CI, 0.4 to 1.2)
      associated with GFR 45 to 60 and 3.2 (1.7 to 6.4) associated with GFR 15 to 44 as
      compared with GFR >60 mL/min/1.73 m(2), whereas those based on the Mayo Clinic
      equation were 2.3 (1.1 to 4.7) and 3.3 (1.6 to 7.1), respectively. The adjusted
      ORs for Barthel Index <or=75 or death after 1 year were 0.8 (0.5 to 1.5) and 2.1
      (0.9 to 4.8) by the Modification of Diet in Renal Disease equation and 1.9 (0.8
      to 4.4) and 3.9 (1.5 to 11.0) by the Mayo Clinic equation, respectively.
      CONCLUSIONS: CKD is a strong independent predictor of mortality and poor outcome
      in patients with acute stroke. The estimation of the prevalence of CKD and of the
      GFR cutoffs associated with poor outcome depend on the equation used to estimate
      GFR.

PMID- 19182073
TI  - Genetic variation in the lymphotoxin-alpha pathway and the risk of ischemic
      stroke in European populations.
AB  - BACKGROUND AND PURPOSE: Several genes involved in the lymphotoxin-alpha cascade
      (LTA, LGALS2, and PSMA6) have been linked with the risk of myocardial infarction.
      Here, we present a comprehensive analysis of these genes in patients with
      ischemic stroke (IS). METHODS: Twenty-three single nucleotide polymorphisms
      (SNPs) from LTA, LGALS2, and PSMA6 were genotyped in 601 German IS patients and
      736 matched controls. SNPs and haplotypes were tested for association with
      overall IS, large vessel stroke, and cardioembolic stroke. Significant
      associations were replicated in an independent sample of 843 IS cases and 933
      controls from the UK. RESULTS: Only one SNP (rs1048990 in PSMA6) showed
      association with overall IS, but this was not replicated in the UK sample. Three
      SNPs showed significant associations with stroke subtypes (P<0.05), but none of
      these associations could be replicated in the UK population. CONCLUSIONS: Genetic
      variation in the lymphotoxin-alpha cascade (LTA, LGALS2, and PSMA6) is not a
      major risk factor for IS.

PMID- 19182074
TI  - MRA for carotid artery stenosis.

PMID- 19182075
TI  - Statins in the management of aneurysmal subarachnoid hemorrhage--not (yet) a
      standard of care.

PMID- 19182076
TI  - Meta-analysis of statins for aneurysmal subarachnoid hemorrhage falls short.

PMID- 19182077
TI  - Blockage of the renin-angiotensin system in the secondary prevention of stroke:
      beneficial effects beyond blood pressure reduction?

PMID- 19182078
TI  - Personal reflections from a front-row seat at the greatest show on earth (life):
      part II (stroke research commentary).

PMID- 19182079
TI  - The effectiveness of the Bobath concept in stroke rehabilitation: what is the
      evidence?
AB  - BACKGROUND AND PURPOSE: In the Western world, the Bobath Concept or
      neurodevelopmental treatment is the most popular treatment approach used in
      stroke rehabilitation, yet the superiority of the Bobath Concept as the optimal
      type of treatment has not been established. This systematic review of randomized,
      controlled trials aimed to evaluate the available evidence for the effectiveness
      of the Bobath Concept in stroke rehabilitation. Method- A systematic literature
      search was conducted in the bibliographic databases MEDLINE and CENTRAL (March
      2008) and by screening the references of selected publications (including
      reviews). Studies in which the effects of the Bobath Concept were investigated
      were classified into the following domains: sensorimotor control of upper and
      lower limb; sitting and standing, balance control, and dexterity; mobility;
      activities of daily living; health-related quality of life; and cost
      effectiveness. Due to methodological heterogeneity within the selected studies,
      statistical pooling was not considered. Two independent researchers rated all
      retrieved literature according to the Physiotherapy Evidence Database (PEDro)
      scale from which a best evidence synthesis was derived to determine the strength
      of the evidence for both effectiveness of the Bobath Concept and for its
      superiority over other approaches. RESULTS: The search strategy initially
      identified 2263 studies. After selection based on predetermined criteria,
      finally, 16 studies involving 813 patients with stroke were included for further
      analysis. There was no evidence of superiority of Bobath on sensorimotor control
      of upper and lower limb, dexterity, mobility, activities of daily living, health
      related quality of life, and cost-effectiveness. Only limited evidence was found
      for balance control in favor of Bobath. Because of the limited evidence
      available, no best evidence synthesis was applied for the health-related quality
      of-life domain and cost-effectiveness. CONCLUSIONS: This systematic review
      confirms that overall the Bobath Concept is not superior to other approaches.
      Based on best evidence synthesis, no evidence is available for the superiority of
      any approach. This review has highlighted many methodological shortcomings in the
      studies reviewed; further high-quality trials need to be published. Evidence
      based guidelines rather than therapist preference should serve as a framework
      from which therapists should derive the most effective treatment.

PMID- 19182080
TI  - Stent placement in acute cerebral artery occlusion: use of a self-expandable
      intracranial stent for acute stroke treatment.
AB  - BACKGROUND AND PURPOSE: Stent placement has been applied in small case series as
      a rescue therapy in combination with different thrombolytic agents, percutaneous
      balloon angioplasty (PTA), and mechanical thromboembolectomy (MT) in acute stroke
      treatment. These studies report a considerable mortality and a high rate of
      intracranial hemorrhages when balloon-mounted stents were used. This study was
      performed to evaluate feasibility, efficacy, and safety of intracranial artery
      recanalization for acute ischemic stroke using a self-expandable stent. METHODS:
      All patients treated with an intracranial stent for acute cerebral artery
      occlusion were included. Treatment comprised intraarterial thrombolysis,
      thromboaspiration, MT, PTA, and stent placement. Recanalization result was
      assessed by follow-up angiography immediately after stent placement.
      Complications related to the procedure and outcome at 3 months were assessed.
      RESULTS: Twelve patients (median NIHSS 14, mean age 63 years) were treated with
      intracranial stents for acute ischemic stroke. Occlusions were located in the
      posterior vertebrobasilar circulation (n=6) and in the anterior circulation
      (n=6). Stent placement was feasible in all procedures and resulted in partial or
      complete recanalization (TIMI 2/3) in 92%. No vessel perforations, subarachnoid,
      or symptomatic intracerebral hemorrhages occurred. One dissection was found after
      thromboaspiration and PTA. Three patients (25%) had a good outcome (mRS 0 to 2),
      3 (25%) a moderate outcome (mRS 3), and 6 (50%) a poor outcome (mRS 4 to 6).
      Mortality was 33.3%. CONCLUSIONS: Intracranial placement of a self-expandable
      stent for acute ischemic stroke is feasible and seems to be safe to achieve
      sufficient recanalization.

PMID- 19182081
TI  - A systematic review on outcome after stenting for intracranial atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Angioplasty and stenting is increasingly being used for
      the treatment of intracranial stenoses. Based on a literature search (01/1998 to
      04/2008) we sought to determine the immediate and long-term outcomes, as well as
      the durability of this procedure. SUMMARY OF REVIEW: We identified 31 studies
      dealing with 1177 procedures, which had mainly been performed in patients with a
      symptomatic (98%) intracranial high-grade stenosis (mean: 78+/-7%) at high
      technical success rates (median: 96%; interquartile range [IQR]: 90% to 100%).
      The periprocedural minor or major stroke and death rates ranged from 0% to 50%
      with a median of 7.7% (IQR: 4.4% to 14.3%). Periprocedural complications were
      significantly higher in the posterior versus the anterior circulation (12.1%,
      versus 6.6%, P<0.01, odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.21 to
      3.10), but did not differ between patients treated with a balloon-mounted (n=906)
      versus those who had been treated with a self-expandable stent (n=271; 9.5%
      versus 7.7%, P=0.47, OR: 1.15, CI:0.76 to 2.05). Restenosis >50% occurred more
      frequently after the use of a self-expandable stent (16/92; 17.4%, mean follow-up
      time: 5.4 months) than a balloon-mounted stent (61/443; 13.8%, mean follow-up
      time: 8.7 months; P<0.001, log-rank test). CONCLUSIONS: Although intracranial
      stenting appears to be feasible, adverse events vary widely. Against the
      background of the results of this review yielding a high rate of restenoses and
      no clear impact of new stent devices on outcome, the widespread application of
      intracranial stenting outside the setting of randomized trials and in
      inexperienced centers currently does not seem to be justified.

PMID- 19182082
TI  - Would self-expanding stent occlude middle cerebral artery perforators?
AB  - BACKGROUND AND PURPOSE: A major concern of intracranial stenting is perforator
      infarction. It is unclear whether the sustained radial force of a self-expanding
      stent or subsequent stent restenosis would cause late occlusion of perforators.
      METHODS: We compared the baseline and poststent (>or=4 months) MRI scans of
      patients who underwent self-expanding stenting for recurrent ischemic symptoms
      attributed to a MCA stenosis >or=60%. New infarcts in the ipsilateral
      striatocapsular region were recorded. RESULTS: MCA stenting was technically
      successful in 23 of 24 recruited patients. No new perforator territory infarct
      was found in follow-up MRI scans of all recruited patients. Postoperatively, all
      patients reported no further TIA or stroke over a median follow-up of 15 months.
      CONCLUSIONS: The use of a self-expanding stent in patients with high-grade MCA
      stenosis may not pose a major risk to the perforators.

PMID- 19182083
TI  - Apoptotic mechanisms after cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Traditionally, cell death after cerebral ischemia was
      considered to be exclusively necrotic in nature, but research over the past
      decade has revealed that after a stroke, many neurons in the ischemic penumbra
      will undergo apoptosis. SUMMARY OF REVIEW: This brief review provides a general
      overview and update of various signaling pathways in the development of apoptosis
      in ischemic lesions. Cerebral ischemia triggers two general pathways of
      apoptosis: the intrinsic pathway, originating from mitochondrial release of
      cytochrome c and associated stimulation of caspase-3; and the extrinsic pathway,
      originating from the activation of cell surface death receptors, resulting in the
      stimulation of caspase-8. Although many of the key apoptotic proteins have been
      identified, our understanding of the complex underlying mechanisms remains poor
      and hence treatment of stroke patients by manipulating apoptotic pathways remains
      a daunting task. However, recent advances in the field have helped broaden our
      knowledge of apoptosis after cerebral ischemia. Further to the simplistic concept
      that stroke-induced apoptosis occurs predominantly in neurons and is caspase
      dependent, accumulating evidence now indicates that apoptosis is prevalent in
      nonneuronal cells and that caspase-independent mechanisms also play a key role.
      CONCLUSIONS: Although the ischemic penumbra is under threat of infarction, it is
      potentially salvageable and thus represents an opportunity for therapeutic
      intervention.

PMID- 19182084
TI  - Ice-cold saline for the induction of mild hypothermia in patients with acute
      ischemic stroke: a pilot study.
AB  - BACKGROUND AND PURPOSE: Neuroprotective effects of induced hypothermia depend on
      its time point of initiation after acute brain injury. Preliminary studies in
      cardiac arrest patients indicate that rapid infusion of ice cold saline (ICS) is
      safe and effective for induction of hypothermia. We investigated its use in
      patients with acute ischemic stroke (AIS). METHODS: Patients (n=10) with AIS were
      included within 3 hours after symptom onset. After cranial CT, they were treated
      if indicated-with rt-PA. ICS of 4 degrees C (25 mL/kg body weight) was
      administered via peripheral intravenous lines. Patients received
      buspirone/pethidine to prevent and treat shivering. After infusion of the target
      volume of ICS, no further efforts were made to maintain hypothermia by other
      methods. RESULTS: Ten patients with a median National Institutes of Health Stroke
      Scale (NIHSS) score of 5.5 (range 4 to 12) on admission were included into the
      study. Nine patients were treated with thrombolysis within a time window of 104+/
      25 minutes. A mean amount of 2163+/-256 mL ICS was infused 17+/-11 minutes after
      rt-PA infusion had started. Tympanic temperature dropped significantly by a
      maximum of 1.6+/-0.3 degrees C (P<0.005) at 52+/-16 minutes after ICS was
      started. The procedure was well tolerated. The NIHSS score improved significantly
      to a median of 1 (range 1 to 15) at discharge compared to admission (P<0.02).
      CONCLUSIONS: This pilot study suggests that rapid ICS infusions in combination
      with pethidine and buspirone lower the body temperature significantly without
      major side effects.

PMID- 19182085
TI  - Retrograde embolism from the descending aorta: visualization by multidirectional
      3D velocity mapping in cryptogenic stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the role of
      plaques >or=4 mm and thrombi (complex plaques) in the descending aorta (DAo) as
      an embolic high-risk source for stroke. METHODS: In 63 acute stroke patients
      scheduled for TEE, territory and embolic pattern of brain ischemia were
      prospectively assessed. Multidirectional 3D MRI velocity mapping of the aorta was
      performed to correlate the extent of retrograde diastolic blood flow with the
      distance of complex DAo plaques from the left subclavian artery (LSA). Embolic
      risk from the DAo was present for (1) retrograde flow connecting complex DAo
      plaques with the LSA, (2) embolic pattern of brain ischemia in a territory
      supplied by the left vertebral artery, and (3) stroke that could not be explained
      by other means. RESULTS: 33 of 63 patients had complex DAo plaques (distance to
      LSA 28.1+/-29.9 mm). Mean retrograde flow in these subjects was 26.2+/-12.3 mm.
      In 20 of 63 patients (31.7%) retrograde flow connected complex DAo plaques with
      the LSA. In 4 of these 20 patients (20%) with an embolic stroke in the territory
      of the brain stem, cerebellum or posterior cerebral artery, etiology could not be
      explained by other means. CONCLUSIONS: Substantial diastolic retrograde flow
      originating from complex plaques in the descending aorta was detected by
      multidirectional 3D MRI velocity mapping and constitutes a stroke mechanism that
      was previously not demonstrable.

PMID- 19182086
TI  - Brain lesions in cerebral venous sinus thrombosis.
AB  - BACKGROUND AND PURPOSE: Analyze the relationship between the location and extent
      of sinus thrombosis and presence and severity of brain lesions. METHODS:
      Retrospective chart and neuroimaging review of patients with documented CVST. A
      CVST score was devised to quantify the extent of cerebral venous sinus
      thrombosis. RESULTS: Nineteen of 56 (34%) patients had brain lesions. The extent
      of sinus thrombus was associated with increased risk of brain lesions (CVST score
      1.9 among patients without brain lesions versus 3.1 in those with lesions;
      P=0.006). Age, sex, and acquired or hereditary thrombophilias were not associated
      with the risk of parenchymal lesions. Functional outcomes were favorable even in
      patients with extensive CVST and parenchymal lesions at presentation.
      CONCLUSIONS: The extent of the sinus involvement correlates with the risk of
      brain lesions in patients with CVST, but additional factors might also contribute
      to their occurrence.

PMID- 19182087
TI  - Arterial wall enhancement overlying carotid plaque on CT angiography correlates
      with symptoms in patients with high grade stenosis.
AB  - BACKGROUND AND PURPOSE: The degree of internal carotid artery (ICA) stenosis is
      an established primary risk factor for embolic stroke. Recent publications
      suggest that inflammatory features may also play an important role. Our purpose
      was to correlate acute neurological symptoms with either carotid artery wall
      enhancement or plaque calcification, on axial CT angiographic source images (CTA
      SI) of patients with severe (>or=70%) ICA stenosis. METHODS: 75 consecutive
      patients with >or=70% ICA stenosis on CTA-SI were identified. Each case was
      classified as symptomatic (n=37) or asymptomatic (n=38), and as having either
      calcified or noncalcified plaque. The latter group was stratified into those with
      versus without arterial wall enhancement, measured in absolute and relative
      Hounsfield Units (HU). RESULTS: Calcified plaque was present in 39% (15/38) of
      the symptomatic patients and in 62% (23/37) of the asymptomatic patients
      (P=0.065). Of the 37 patients without calcified plaque, carotid wall enhancement
      was observed in 83% (19/23) of the symptomatic, but only in 57% (8/14) of the
      asymptomatic patients (P=0.041). When the "calcified plaque" and "no carotid wall
      enhancement" groups were pooled, versus the "carotid wall enhancement" group,
      enhancement was more likely in symptomatic patients (OR 3.625, CI 95% 1.3229 to
      9.93, P=0.01 Fisher Exact test). CONCLUSIONS: In patients with severe ICA
      stenosis, additional stratification of stroke risk may be possible based on the
      presence of carotid wall enhancement on CTA-SI. Patients with carotid wall
      enhancement are more likely to be symptomatic, compared to those with either
      calcified plaque or no enhancement.

PMID- 19182088
TI  - May-Thurner syndrome in patients with cryptogenic stroke and patent foramen
      ovale: an important clinical association.
AB  - BACKGROUND AND PURPOSE: We aimed to investigate the incidence of May-Thurner
      syndrome in patients with cryptogenic stroke with patent foramen ovale. METHODS:
      This was a retrospective study. All consecutive patients with cryptogenic stroke
      having undergone patent foramen ovale closure from January 1, 2002, to December
      31, 2007, at our institute were included in this study. Pelvic magnetic resonance
      venography studies of all patients were reviewed to determine if features of May
      Thurner syndrome were present. Medical records and invasive venography studies of
      all patients were reviewed when available. All patients with May-Thurner syndrome
      features on magnetic resonance venography were reviewed by a vascular medicine
      specialist to define any previous incidence of deep vein thrombosis or any signs
      of chronic venous insufficiency. All patients also had lower limb venous duplex
      performed to rule out lower limb venous thrombosis. RESULTS: A total of 470
      patients from January 1, 2002, until December 31, 2007, with cryptogenic stroke
      underwent patent foramen ovale closure at our institute. Thirty patients (6.3%)
      had features consistent with May-Thurner syndrome on magnetic resonance
      venography. These patients were predominantly female (80%) with a mean age of
      43.6+/-11.9 years. Twelve patients (40%) had abnormalities in their laboratory
      thrombophilia evaluation and 13 females (54.1%) were taking hormone-related birth
      control pills. Only 2 patients had a history and signs of chronic venous
      insufficiency. All patent foramen ovales demonstrated right-to-left shunting on
      transesophageal echocardiography. Atrial septal aneurysms/hypermobile atrial
      septa were present in 70% of patients with May-Thurner syndrome. CONCLUSIONS: May
      Thurner syndrome has an important clinical association with cryptogenic stroke
      and patent foramen ovale.

PMID- 19182089
TI  - Resident-based acute stroke protocol is expeditious and safe.
AB  - BACKGROUND AND PURPOSE: The decision to administer tPA to acute stroke patients
      is frequently made by stroke attendings or fellows, but placing residents in this
      position may make tPA delivery more efficient. METHODS: Beginning in 2004, we
      instituted a resident-based acute stroke protocol placing neurology residents in
      decision-making roles. Time-intervals, symptomatic hemorrhage rate, and discharge
      locations were prospectively collected and compared between two epochs, before
      and after 2004. RESULTS: 59 acute ischemic stroke patients were treated with tPA
      before protocol initiation (1998 to 2002), while 113 patients were treated after
      protocol initiation (2004 to 2007). The average door-to-needle and onset-to
      needle times were significantly shorter after initiation of the resident-based
      protocol (81 versus 60 minutes [P<0.001] and 138 versus 126 minutes [P<0.05]),
      respectively. Symptomatic hemorrhage rate (5.1% versus 3.5%) and favorable
      discharge location (68% versus 76%) did not differ between the two time periods.
      CONCLUSIONS: A resident-driven tPA protocol, with formal training and quality
      control, is safe and efficient.

PMID- 19182090
TI  - Effect of age on stroke prevention therapy in patients with atrial fibrillation:
      the atrial fibrillation investigators.
AB  - BACKGROUND AND PURPOSE: Stroke risk increases with age in patients who have
      nonvalvular atrial fibrillation. It is uncertain whether the efficacy of stroke
      prevention therapies in atrial fibrillation changes as patients age. The
      objective of this study was to determine the effect of age on the relative
      efficacy of oral anticoagulants (OAC) and antiplatelet (AP) therapy (including
      acetylsalicylic acid and triflusal) on ischemic stroke, serious bleeding, and
      vascular events in patients with atrial fibrillation. METHODS: This is an
      analysis of the Atrial Fibrillation Investigators database, which contains
      patient level-data from randomized trials of stroke prevention in atrial
      fibrillation. We used Cox regression models with age as a continuous variable
      that controlled for sex, year of randomization, and history of cerebrovascular
      disease, diabetes, hypertension, and congestive heart failure. Outcomes included
      ischemic stroke, serious bleeding (intracranial hemorrhage or systemic bleeding
      requiring hospitalization, transfusion, or surgery), and cardiovascular events
      (ischemic stroke, myocardial infarction, systemic embolism, or vascular death).
      RESULTS: The analysis included 8932 patients and 17 685 years of observation from
      12 trials. Patient age increased risk of ischemic stroke (adjusted hazard ratio
      per decade increase 1.45; 95% CI, 1.26 to 1.66), serious bleeding (1.61; 1.47 to
      1.77), and cardiovascular events (1.43; 1.33 to 1.53). Compared with placebo, OAC
      and AP significantly reduced the risk of ischemic stroke (OAC, 0.36; 0.29 to
      0.45; AP, 0.81; 0.72 to 0.90) and cardiovascular outcomes (OAC, 0.59; 0.52 to
      0.66; AP, 0.81; 0.75 to 0.88), whereas OAC increased risk of serious bleeding
      (1.56; 1.03 to 2.37). The relative benefit of OAC versus placebo or AP did not
      vary by patient age for any outcome. Compared with placebo, the relative benefit
      of AP for preventing ischemic stroke decreased significantly as patients aged
      (P=0.01). CONCLUSIONS: As patients with atrial fibrillation age, the relative
      efficacy of AP to prevent ischemic stroke appears to decrease, whereas it does
      not change for OAC. Because stroke risk increases with age, the absolute benefit
      of OAC increases as patients get older.

PMID- 19182091
TI  - Estimating the long-term costs of ischemic and hemorrhagic stroke for Australia:
      new evidence derived from the North East Melbourne Stroke Incidence Study
      (NEMESIS).
AB  - BACKGROUND AND PURPOSE: Stroke is associated with considerable societal costs.
      Cost-of-illness studies have been undertaken to estimate lifetime costs; most
      incorporating data up to 12 months after stroke. Costs of stroke, incorporating
      data collected up to 12 months, have previously been reported from the North East
      Melbourne Stroke Incidence Study (NEMESIS). NEMESIS now has patient-level
      resource use data for 5 years. We aimed to recalculate the long-term resource
      utilization of first-ever stroke patients and compare these to previous estimates
      obtained using data collected to 12 months. METHODS: Population structure, life
      expectancy, and unit prices within the original cost-of-illness models were
      updated from 1997 to 2004. New Australian stroke survival and recurrence data up
      to 10 years were incorporated, as well as cross-sectional resource utilization
      data at 3, 4, and 5 years from NEMESIS. To enable comparisons, 1997 costs were
      inflated to 2004 prices and discounting was standardized. RESULTS: In 2004, 27
      291 ischemic stroke (IS) and 4291 intracerebral hemorrhagic stroke (ICH) first
      ever events were estimated. Average annual resource use after 12 months was
      AU$6022 for IS and AU$3977 for ICH. This is greater than the 1997 estimates for
      IS (AU$4848) and less than those for ICH (previously AU$10 692). The recalculated
      average lifetime costs per first-ever case differed for IS (AU$57 106 versus
      AU$52 855 [1997]), but differed more for ICH (AU$49 995 versus AU$92 308 [1997]).
      CONCLUSIONS: Basing lifetime cost estimates on short-term data overestimated the
      costs for ICH and underestimated those for IS. Patterns of resource use varied by
      stroke subtype and, overall, the societal cost impact was large.

PMID- 19182092
TI  - Operating environment and USA nursing homes' participation in the subacute care
      market: a longitudinal analysis.
AB  - We examined the impact of environmental factors on USA nursing homes'
      participation in the subacute care market. Findings suggest that the Balanced
      Budget Act of 1997 did not have a significant impact in the participation of
      nursing homes in the subacute care market from 1998 to 2000. However, there was a
      declining trend in the participation of nursing homes in the subacute care market
      after the implementation of Medicare prospective payment system (PPS).
      Furthermore, nursing homes with a higher proportion of Medicare residents were
      more likely to exit the subacute care market after PPS. Results also suggest that
      nursing homes have responded strategically to the environmental demand for
      subacute care services. Nursing homes located in markets with higher Medicare
      managed care penetration were more likely to offer subacute care services.
      Environmental munificence was also an important predictor of nursing home
      innovation into subacute care. Nursing homes in states with higher Medicaid
      reimbursement and those in less competitive markets were more likely to
      participate in the subacute care market.

PMID- 19182093
TI  - What do we know? Limitations of the two methods most commonly used to estimate
      the length of the prospective wait.
AB  - Health service researchers, policy analysts and other commentators have
      overlooked the limitations of existing approaches to the estimation of waiting
      times. If urgent cases are given priority, there are no instances when census
      based data can supply accurate estimates of the length of the prospective wait.
      But there are three occasions when event-based data supply accurate estimates of
      the prospective wait of those who chose to enrol and we can predict the direction
      of error when the relevant conditions are violated if we know whether the list
      was open or closed, and whether it grew in size or shrank. Without this
      additional information, we cannot determine whether the changes we observe over
      time or the differences we see between one list and the next are spurious or not.
      The period life-table provides a timely and bias-free alternative to the existing
      cross-sectional approaches for a modest increase in the complexity of
      calculation.

PMID- 19182094
TI  - The development of an ongoing monitoring and evaluation system in a NORC service
      organization.
AB  - The objective of this study was to describe the development, utilization and
      utility of an ongoing evaluation of a system of coordinated services to persons
      living in two naturally occurring retirement communities (NORCs). The evaluation
      system includes service provision, service utilization and client satisfaction.
      It identifies trends in provided services and determines how services are
      utilized. A continuous monitoring system for reporting and quality improvement
      was developed with the four service agencies associated with the service
      provision system. The monthly data from each agency are compiled and distributed
      in the form of a report. The evaluation project was successful in tailoring the
      reporting system to each agency. Multiple issues arose with staff compliance in
      utilization of the system, but, overall, the system evaluation presents detailed
      feedback on the services provided and helps with continuing development, testing
      of new delivery models, planning, maximizing resource utilization, customer
      service, and attaining and sustaining funding. A system evaluation of an
      organization that provides services to a community is vital to optimizing
      frequency and quality of services. There are many ways to implement system
      evaluations. However, the use of electronic-based records increases the
      likelihood of maintaining and utilizing the system.

PMID- 19182095
TI  - Travel-related costs of population dispersion in the provision of domiciliary
      care to the elderly: a case study in English Local Authorities.
AB  - The aim of this research has been to make a contribution to deliberations
      concerning the relative costs of provision of domiciliary services for the
      elderly in local authorities in England and the implications for funding. The
      main services considered have been day-centre services and home-care services,
      and the particular cost areas investigated have been travel-related costs as
      associated with distances travelled by day-centre vehicles and care workers and
      with worker travelling hours. These costs are influenced by the population
      settlement and dispersion characteristics of the areas served and funding
      mechanisms are needed (and are in place) to compensate service providers.
      However, current mechanisms have been widely criticized and the research reported
      here reaches conclusions about whether such criticisms are justified and how
      improvements might be brought about. The methods used have involved detailed
      operational modelling of the selected services in a sample of local authority
      areas and the generalization of the findings to England as a whole.

PMID- 19182096
TI  - Using the balanced scorecard in the development of community partnerships.
AB  - The benefits of community partnerships have been well established in the health
      service literature. However, measuring these benefits and associated outcomes is
      relatively new. This paper presents an innovative initiative in the application
      of a balanced scorecard framework for measuring and monitoring partnership
      activity at the community level, while adopting principles of evidence-based
      practice to the partnership process. In addition, it serves as an excellent
      example of how organizations can apply scorecard methodology to move away from
      relationship-based partnerships and into new collaborations of which they can
      select - using a formal skill and competency assessment for partnership success.

PMID- 19182097
TI  - Do hospitals practice cream skimming?
AB  - 'Cream skimming' refers to choosing patients for some characteristic(s) other
      than their need for care, which enhances the profitability or reputation of the
      provider. Under capitation or other fixed payment schemes, this often means
      choosing less ill patients. We present a new methodology to measure cream
      skimming by hospitals. Our approach also provides a measure of a hospital's gain
      in productive efficiency by caring for patients with lower illness severity.
      Using a panel of Washington state hospitals, we find evidence that hospitals do
      practice cream skimming. However, we find little evidence to suggest that cream
      skimming varies by hospital size, profit status or time.

PMID- 19182098
TI  - Crassulacean acid metabolism and epiphytism linked to adaptive radiations in the
      Orchidaceae.
AB  - Species of the large family Orchidaceae display a spectacular array of
      adaptations and rapid speciations that are linked to several innovative features,
      including specialized pollination syndromes, colonization of epiphytic habitats,
      and the presence of Crassulacean acid metabolism (CAM), a water-conserving
      photosynthetic pathway. To better understand the role of CAM and epiphytism in
      the evolutionary expansion of tropical orchids, we sampled leaf carbon isotopic
      composition of 1,103 species native to Panama and Costa Rica, performed character
      state reconstruction and phylogenetic trait analysis of CAM and epiphytism, and
      related strong CAM, present in 10% of species surveyed, to climatic variables and
      the evolution of epiphytism in tropical regions. Altitude was the most important
      predictor of photosynthetic pathway when all environmental variables were taken
      into account, with CAM being most prevalent at low altitudes. By creating
      integrated orchid trees to reconstruct ancestral character states, we found that
      C3 photosynthesis is the ancestral state and that CAM has evolved at least 10
      independent times with several reversals. A large CAM radiation event within the
      Epidendroideae, the most species-rich epiphytic clade of any known plant group,
      is linked to a Tertiary species radiation that originated 65 million years ago.
      Our study shows that parallel evolution of CAM is present among subfamilies of
      orchids, and correlated divergence between photosynthetic pathways and epiphytism
      can be explained by the prevalence of CAM in low-elevation epiphytes and rapid
      speciation of high-elevation epiphytes in the Neotropics, contributing to the
      astounding diversity in the Orchidaceae.

PMID- 19182100
TI  - The Plant Cell: 20 years young.

PMID- 19182099
TI  - Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule
      with sustained follicle-stimulating activity and reduced injection frequency.
AB  - BACKGROUND: Recombinant DNA technologies have been used to develop longer-acting
      therapeutic proteins. One approach is to introduce sequences containing
      additional glycosylation sites. Using this technique, a new chimeric gene has
      been developed containing the coding sequences of the FSH beta-subunit and the C
      terminal peptide of the hCG beta-subunit, which bears four O-linked
      oligosaccharide binding sites. Co-expression of the alpha-subunit and the
      chimeric FSH beta-subunit produces a new recombinant molecule, named
      corifollitropin alfa, with a prolonged elimination half-life and enhanced in vivo
      bioactivity compared with wild-type FSH. METHODS: Medline searches by subject and
      additional searching by hand. RESULTS: Initial studies in pituitary suppressed
      female volunteers confirmed the extended half-life of the compound. Phase II
      studies have shown that corifollitropin alfa is able to induce and sustain multi
      follicular growth for an entire week in women undergoing ovarian stimulation
      using GnRH antagonist co-treatment for IVF. Corifollitropin alfa regimens have
      been developed with dosages of 100 and 150 microg, for patients with body weight
      </=60 and >60 kg, respectively. CONCLUSIONS: Corifollitropin alfa is the first
      long-acting hybrid molecule with sustained follicle-stimulating activity
      developed for the induction of multi-follicular growth along with GnRH antagonist
      co-treatment for IVF. This new treatment option may be simpler and more
      convenient for patients compared with conventional long protocols of daily FSH
      injections in combination with GnRH agonist co-treatment. The safety and efficacy
      of such regimens is currently being evaluated in large comparative phase III
      clinical trials. The development of corifollitropin alfa is the first step
      towards a new generation of recombinant gonadotrophins.

PMID- 19182101
TI  - Happy birthday to the Plant Cell.

PMID- 19182102
TI  - Chloroplast RNA editing by pentatricopeptide repeat proteins.

PMID- 19182103
TI  - Breaking up is hard to do: cell separation events involve multiple
      polygalacturonases and multiple hormones.

PMID- 19182105
TI  - Participation of leaky ribosome scanning in protein dual targeting by alternative
      translation initiation in higher plants.
AB  - Postendosymbiotic evolution has given rise to proteins that are multiply targeted
      within the cell. Various mechanisms have been identified to permit the expression
      of proteins encoding distinct N termini from a single gene. One mechanism
      involves alternative translation initiation (aTI). We previously showed evidence
      of aTI activity within the Arabidopsis thaliana organellar DNA polymerase gene
      POLgamma2. Translation initiates at four distinct sites within this gene, two non
      AUG, to produce distinct plastid and mitochondrially targeted forms of the
      protein. To understand the regulation of aTI in higher plants, we used Polgamma2
      as a model to investigate both cis- and trans-acting features of the process.
      Here, we show that aTI in Polgamma2 and other plant genes involves ribosome
      scanning dependent on sequence context at the multiple initiation sites to
      condition specific binding of at least one trans-acting factor essential for site
      recognition. Multiple active translation initiation sites appear to operate in
      several plant genes, often to expand protein targeting. In plants, where the
      mitochondrion and plastid must share a considerable portion of their proteomes
      and coordinate their functions, leaky ribosome scanning behavior provides
      adaptive advantage in the evolution of protein dual targeting and translational
      regulation.

PMID- 19182104
TI  - Pentatricopeptide repeat proteins with the DYW motif have distinct molecular
      functions in RNA editing and RNA cleavage in Arabidopsis chloroplasts.
AB  - The plant-specific DYW subclass of pentatricopeptide repeat proteins has been
      postulated to be involved in RNA editing of organelle transcripts. We discovered
      that the DYW proteins CHLORORESPIRATORY REDUCTION22 (CRR22) and CRR28 are
      required for editing of multiple plastid transcripts but that their DYW motifs
      are dispensable for editing activity in vivo. Replacement of the DYW motifs of
      CRR22 and CRR28 by that of CRR2, which has been shown to be capable of
      endonucleolytic cleavage, blocks the editing activity of both proteins. In
      return, the DYW motifs of neither CRR22 nor CRR28 can functionally replace that
      of CRR2. We propose that different DYW family members have acquired distinct
      functions in the divergent processes of RNA maturation, including RNA cleavage
      and RNA editing.

PMID- 19182106
TI  - Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells.
AB  - Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure
      of humans to HCB produces a number of effects, such as triggering of porphyria,
      increased synthesis of liver microsomal enzymes, neurological symptoms,
      immunological disorders and thyroid dysfunctions. In rats, HCB induced hepatic
      porphyria, neurotoxic effects, and toxic effects on the reproductive system,
      thyroid function, and immune system. HCB is also known to cause tumors of the
      liver, thyroid and mammary gland in laboratory animals. The aim of this study was
      to investigate parameters of thyroid growth regulation, mainly cell proliferation
      and apoptosis in thyroid tissue from HCB (0.1, 1, 10, 100, and 500 mg/kg body
      weight)-treated female Wistar rats. The current study demonstrates that only the
      exposure to the highest HCB dose for 30 days, has adverse effects on thyroid
      endpoints examined related to thyroid gland morphology, and 3,3'5,5'
      tetraiodothyronine (T(4), thyroxine) serum levels, without changes in thyroid
      stimulating hormone concentrations or in thyroid gland weight. Morphological
      changes, included flattened epithelium and increased colloid size compared with
      control tissue. Transforming growth factor (TGF-beta1) mRNA levels, evaluated by
      RT-PCR, revealed a significant upregulation after exposure to HCB (1, 10, 100
      mg/kg body weight). Cell proliferation evaluated by 5'-Br deoxiuridine
      incorporation into DNA, was not altered at any dose. HCB (1, 10, 100 mg/kg body
      weight) induces apoptosis, evaluated by in situ end labeling of fragmented DNA,
      terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick
      end labeling, in rat thyroid glands. This process is associated with dose
      dependent increases in cytochrome c release from the mitochondria and procaspase
      9 processing to its active product. Caspase-8 was not activated. These studies
      indicate that doses of HCB that do not disrupt thyroid economy induce TGF-beta1
      expression and apoptosis in the thyroid gland, involving the mitochondrial
      pathway.

PMID- 19182107
TI  - Ambient particulates alter vascular function through induction of reactive oxygen
      and nitrogen species.
AB  - Previous studies have shown a link between inhaled particulate matter (PM)
      exposure in urban areas and susceptibility to cardiovascular diseases. Although
      an oxidative stress pathway is strongly implicated, the locus of generation of
      reactive oxygen species (ROS) and the mechanisms by which these radicals exert
      their effects remain to be characterized. To test the hypothesis that exposure to
      environmentally relevant inhaled concentrated ambient PM (CAPs) enhances
      atherosclerosis through induction of vascular ROS and reactive nitrogen species.
      High-fat chow fed apolipoprotein E(-/-) mice were exposed to CAPs of less than
      2.5 microm (PM(2.5)) or filtered air (FA), for 6 h/day, 5 days/week, for 4 months
      in Manhattan, NY. Atherosclerotic lesions were analyzed by histomorphometricly.
      Vascular reactivity, superoxide generation, mRNA expression of NADPH
      (nicotinamide adenine dinucleotide phosphate, reduced) oxidase subunits,
      inducible nitric oxide synthase, endothelial nitric oxide synthase, and GTP
      cyclohydrolase I were also assessed. Manhattan PM(2.5) CAPs were characterized by
      higher concentrations of organic and elemental carbon. Analysis of vascular
      responses revealed significantly decreased phenylephrine constriction in CAPs
      exposed mice, which was restored by a soluble guanine cyclase inhibitor 1H
      [1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. Vascular relaxation to A23187, but not
      to acetylcholine, was attenuated in CAPs mice. Aortic expression of NADPH oxidase
      subunits (p47(phox) and rac1) and iNOS were markedly increased, paralleled by
      increases in superoxide generation and extensive protein nitration in the aorta.
      The composite plaque area of thoracic aorta was significantly increased with
      pronounced macrophage infiltration and lipid deposition in the CAPs mice. CAPs
      exposure in Manhattan alters vasomotor tone and enhances atherosclerosis through
      NADPH oxidase dependent pathways.

PMID- 19182108
TI  - An unusual sinonasal tumor: soft tissue perineurioma.
AB  - Soft tissue perineuriomas are an unusual type of peripheral nerve sheath tumors
      distinct from schwannomas and neurofibromas, with interesting histologic
      findings. They are not well characterized on radiographic examination. We report
      this case of a patient with sinonasal perineurioma to help define the imaging and
      pathologic features of this rare head and neck tumor.

PMID- 19182109
TI  - Feeling no pain.

PMID- 19182110
TI  - Video analysis of anterior cruciate ligament injury: abnormalities in hip and
      ankle kinematics.
AB  - BACKGROUND: Most anterior cruciate ligament research is limited to variables at
      the knee joint and is performed in the laboratory setting, often with subjects
      postinjury. There is a paucity of information on the position of the hip and
      ankle during noncontact anterior cruciate ligament injury. HYPOTHESIS: When
      landing after maneuvers, athletes with anterior cruciate ligament injury
      (subjects) show a more flatfooted profile and more hip flexion than uninjured
      athletes (controls). STUDY DESIGN: Case control study; Level of evidence, 3.
      METHODS: Data from 29 videos of subjects were compared with data from 27 videos
      of controls performing similar maneuvers. Joint angles were analyzed in 5
      sequential frames in sagittal or coronal planes, starting with initial ground
      foot contact. Hip, knee, and ankle joint angles were measured in each sequence in
      the sagittal plane and hip and knee angles in the coronal plane with computer
      software. The portion of the foot first touching the ground and the number of
      sequences required for complete foot-ground contact were assessed. Significance
      was set at P< .05. RESULTS: In sagittal views, controls first contacted the
      ground with the forefoot; subjects had first ground contact with the hind-foot or
      entirely flatfooted, attained the flatfoot position significantly sooner, had
      significantly less plantar-flexed ankle angles at initial contact, and had a
      significantly larger mean hip flexion angle at the first 3 frames. In coronal
      views, no significant differences in knee abduction (initial contact) or hip
      abduction angle were found between groups; knee abduction was relatively
      unchanged in controls but progressed in subjects. CONCLUSION: Initial ground
      contact flatfooted or with the hindfoot, knee abduction and increased hip flexion
      may be risk factors for anterior cruciate ligament injury.

PMID- 19182111
TI  - Declining incidence of catastrophic cervical spine injuries in French rugby: 1996
      2006.
AB  - PURPOSE: To investigate the incidence and the risk factors of catastrophic
      cervical spine injuries in French rugby. STUDY DESIGN: Descriptive epidemiology
      study. METHODS: The patients included had cervical spine injuries causing
      neurological disorder classified from the ASIA scale, grade A to D. A
      retrospective review of all cases that occurred between the 1996-1997 and the
      2005-2006 seasons was made. Circumstances of the injuries and of the clinical
      outcome were collected by interview. RESULTS: There were 37 cases of catastrophic
      cervical spine injuries in French rugby for the last 10 years. The incidence of
      the cervical spine injuries decreased during this period. The rates of injury
      were 2.1 per 100,000 players per year during the 1996-1997 season and 1.4 during
      the 2005-2006 season (P < .01). The scrum was a major cause of injury, accounting
      for 51.3% (19/37). The forwards represented 89.2% (33/37) of the injured players.
      The hookers were involved in 37.8% (14/37) of the cases. The measures of
      prevention with the modification of the rules of scrum and the creation of a
      medical certificate required for players to play in the front row must have been
      successful. CONCLUSION: The incidence of disabling cervical spine injuries in
      French rugby has decreased for the last 10 years, which is linked to the
      decreasing incidence of injuries in the scrum. This epidemiological study shows
      the effectiveness of the preventive measures on cervical spine injuries in French
      rugby players. A national register of catastrophic cervical spine injuries
      extends our epidemiological observations.

PMID- 19182113
TI  - Re: Outcome of single-bundle versus double-bundle reconstruction of the anterior
      cruciate ligament: a meta-analysis.

PMID- 19182115
TI  - Re: Sex-based differences in the anthropometric characteristics of the anterior
      cruciate ligament and its relation to intercondylar notch geometry: a cadaveric
      study.

PMID- 19182118
TI  - Timing accuracy of Web experiments: a case study using the WebExp software
      package.
AB  - Although Internet-based experiments are gaining in popularity, most studies rely
      on directly evaluating participants' responses rather than response times. In the
      present article, we present two experiments that demonstrate the feasibility of
      collecting response latency data over the World-Wide Web using WebExp-a software
      package designed to run psychological experiments over the Internet. Experiment 1
      uses WebExp to collect measurements for known time intervals (generated using
      keyboard repetition). The resulting measurements are found to be accurate across
      platforms and load conditions. In Experiment 2, we use WebExp to replicate a lab
      based self-paced reading study from the psycholinguistic literature. The data of
      the Web-based replication correlate significantly with those of the original
      study and show the same main effects and interactions. We conclude that WebExp
      can be used to obtain reliable response time data, at least for the self-paced
      reading paradigm.

PMID- 19182120
TI  - MLP: a MATLAB toolbox for rapid and reliable auditory threshold estimation.
AB  - In this article, we present MLP, a MATLAB toolbox enabling auditory thresholds
      estimation via the adaptive maximum likelihood procedure proposed by David Green
      (1990, 1993). This adaptive procedure is particularly appealing for those
      psychologists who need to estimate thresholds with a good degree of accuracy and
      in a short time. Together with a description of the toolbox, the present text
      provides an introduction to the threshold estimation theory and a theoretical
      explanation of the maximum likelihood adaptive procedure. MLP comes with a
      graphical interface, and it is provided with several built-in, classic
      psychoacoustics experiments ready to use at a mouse click.

PMID- 19182119
TI  - Using the World-Wide Web to obtain large-scale word norms: 190,212 ratings on a
      set of 2,654 German nouns.
AB  - This article presents a new database of 2,654 German nouns rated by a sample of
      3,907 subjects on three psycholinguistic attributes: concreteness, valence, and
      arousal. As a new means of data collection in the field of psycholinguistic
      research, all ratings were obtained via the Internet, using a tailored Web
      application. Analysis of the obtained word norms showed good agreement with two
      existing norm sets. A cluster analysis revealed a plausible set of four classes
      of nouns: abstract concepts, aversive events, pleasant activities, and physical
      objects. In an additional application example, we demonstrate the usefulness of
      the database for creating parallel word lists whose elements match as closely as
      possible. The complete database is available for free from ftp://ftp.uni
      duesseldorf.de/pub/psycho/lahl/WWN. Moreover, the Web application used for data
      collection is inherently capable of collecting word norms in any language and is
      going to be released for public use as well.

PMID- 19182121
TI  - ALTSim: a MATLAB simulator for current associative learning theories.
AB  - ALTSim is a MATLAB-based simulator of several associative learning models,
      including Pearce's configural model, the extended configural model, the Rescorla
      Wagner model, the unique cue hypothesis, the modified unique cue hypothesis, the
      replaced elements model, and Harris's elemental model. It allows for specifying
      all relevant parameters, as well as exact stimulus sequences by graphical user
      interfaces. It is an easy-to-use tool that facilitates evaluating and comparing
      the featured associative learning models. ALTSim is available free of charge from
      www.staff.uni-marburg.de/~lachnit/ALTSim/.

PMID- 19182122
TI  - A SAS macro for statistical power calculations in meta-analysis.
AB  - Although statistical power is often considered in the design of primary research
      studies, it is rarely considered in meta-analysis. Background and guidelines are
      provided for conducting power analysis in meta-analysis, followed by the
      presentation of a SAS macro that calculates power using the methods described by
      Hedges and Pigott (2001, 2004). Several detailed examples are given, including
      input statements and output. Practical issues in the application of power
      analysis to meta-analysis are discussed. The macro and examples may be downloaded
      as supplemental materials for this article from brm.psychonomic
      journals.org/content/supplemental.

PMID- 19182123
TI  - SPSS programs for the measurement of nonindependence in standard dyadic designs.
AB  - Dyadic research is becoming more common in the social and behavioral sciences.
      The most common dyadic design is one in which two persons are measured on the
      same set of variables. Very often, the first analysis of dyadic data is to
      determine the extent to which the responses of the two persons are correlated
      that is, whether there is nonindependence in the data. We describe two user
      friendly SPSS programs for measuring nonindependence of dyadic data. Both
      programs can be used for distinguishable and indistinguishable dyad members.
      Inter1.sps is appropriate for interval measures. Inter2.sps applies to
      categorical variables. The SPSS syntax and data files related to this article may
      be downloaded as supplemental materials from brm.psychonomic
      journals.org/content/supplemental.

PMID- 19182124
TI  - Variation in scatterplot displays.
AB  - Scatterplots are typically constructed for the purpose of showing the association
      between two variables. We argue that such scatterplots should not vary in ways
      that are unrelated to the degree of association. Noting that the publication
      standards for the preparation of scatterplots are minimal, we review empirical
      literature that shows that a number of arbitrary features of scatterplots
      influence the inferences drawn by users. We discuss nine such features. We also
      review the literature that recommends how scatterplots should be prepared, and we
      examine 221 scatterplots published in recent journals. There was considerable
      variation among those published scatterplots. This article concludes with a call
      for further standardization by way of flexible guidelines.

PMID- 19182125
TI  - Detection of interactions between a dichotomous moderator and a continuous
      predictor in moderated multiple regression with heterogeneous error variance.
AB  - Moderated multiple regression (MMR) has been widely used to investigate the
      interaction or moderating effects of a categorical moderator across a variety of
      subdisciplines in the behavioral and social sciences. In view of the frequent
      violation of the homogeneity of error variance assumption in MMR applications,
      the weighted least squares (WLS) approach has been proposed as one of the
      alternatives to the ordinary least squares method for the detection of the
      interaction effect between a dichotomous moderator and a continuous predictor.
      Although the existing result is informative in assuring the statistical accuracy
      and computational ease of the WLS-based method, no explicit algebraic formulation
      and underlying distributional details are available. This article aims to
      delineate the fundamental properties of the WLS test in connection with the well
      known Welch procedure for regression slope homogeneity under error variance
      heterogeneity. With elaborately systematic derivation and analytic assessment, it
      is shown that the notion of WLS is implicitly embedded in the Welch approach.
      More importantly, extensive simulation study is conducted to demonstrate the
      conditions in which the Welch test will substantially outperform the WLS method;
      they may yield different conclusions. Welch's solution to the Behrens-Fisher
      problem is so entrenched that the use of its direct extension within the linear
      regression framework can arguably be recommended. In order to facilitate the
      application of Welch's procedure, the SAS and R computing algorithms are
      presented. The study contributes to the understanding of methodological variants
      for detecting the effect of a dichotomous moderator in the context of moderated
      multiple regression. Supplemental materials for this article may be downloaded
      from brm.psychonomic-journals.org/content/supplemental.

PMID- 19182126
TI  - Measuring discriminability when there are multiple sources of bias.
AB  - Performance measures such as log d and d' aim to measure stimulus
      discriminability independently of response bias in conditional discrimination
      tasks, including the yes/no signal-detection procedure. However, they assume only
      one dimension of bias (e.g., response color) and do not account for bias on
      additional dimensions (e.g., response side). Such bias reduces log d, thus
      violating the statistical independence of discriminability and bias measurements.
      We modified log d to account for side bias and reanalyzed previous side-biased
      data. With strong side bias, the modified log d differed enough from the standard
      log d to potentially alter the conclusions of an experiment. Simulations showed
      that the modified log d produces discriminability estimates that are more
      accurate and bias-independent than the standard log d calculation.

PMID- 19182127
TI  - A comparison of linear and mixture models for discriminant analysis under
      nonnormality.
AB  - Methods for discriminant analysis were compared with respect to classification
      accuracy under nonnormality through Monte Carlo simulation. The methods compared
      were linear discriminant analyses based both on raw scores and on ranks; linear
      logistic discrimination; and mixture discriminant analysis. Linear discriminant
      analysis and linear logistic discrimination were suboptimal in a number of
      scenarios with skewed predictors. Linear discriminant analysis based on ranks
      yielded the highest rates of classification accuracy in only a limited number of
      situations and did not produce a practically important advantage over competing
      methods. Mixture discriminant analysis, with a relatively small number of
      components in each group, attained relatively high rates of classification
      accuracy and was most useful for conditions in which skewed predictors had
      relatively small values of kurtosis.

PMID- 19182128
TI  - Adaptive Visual Analog Scales (AVAS): a modifiable software program for the
      creation, administration, and scoring of visual analog scales.
AB  - The Adaptive Visual Analog Scales is a freely available computer software package
      designed to be a flexible tool for the creation, administration, and automated
      scoring of both continuous and discrete visual analog scale formats. The
      continuous format is a series of individual items that are rated along a solid
      line and scored as a percentage of distance from one of the two anchors of the
      rating line. The discrete format is a series of individual items that use a
      specific number of ordinal choices for rating each item. This software offers
      separate options for the creation and use of standardized instructions, practice
      sessions, and rating administration, all of which can be customized by the
      investigator. A unique participant/patient ID is used to store scores for each
      item, and individual data from each administration are automatically appended to
      that scale's data storage file. This software provides flexible, time-saving
      access for data management and/or importing data into statistical packages. This
      tool can be adapted so as to gather ratings for a wide range of clinical and
      research uses and is freely available at www.nrlc-group.net.

PMID- 19182130
TI  - NASA TLX: software for assessing subjective mental workload.
AB  - The NASA Task Load Index (TLX) is a popular technique for measuring subjective
      mental workload. It relies on a multidimensional construct to derive an overall
      workload score based on a weighted average of ratings on six subscales: mental
      demand, physical demand, temporal demand, performance, effort, and frustration
      level. A program for implementing a computerized version of the NASA TLX is
      described. The software version assists in simplifying collection,
      postprocessing, and storage of raw data. The program collects raw data from the
      subject and calculates the weighted (or unweighted) workload score, which is
      output to a text file. The program can also be tailored to a specific experiment
      using a simple input text file, if desired. The program was designed in Visual
      Studio 2005 and is capable of running on a Pocket PC with Windows CE or on a PC
      with Windows 2000 or higher. The NASA TLX program is available for free download.

PMID- 19182129
TI  - Tachistoscopic exposure and masking of real three-dimensional scenes.
AB  - Although there are many well-known forms of visual cues specifying absolute and
      relative distance, little is known about how visual space perception develops at
      small temporal scales. How much time does the visual system require to extract
      the information in the various absolute and relative distance cues? In this
      article, we describe a system that may be used to address this issue by
      presenting brief exposures of real, three-dimensional scenes, followed by a
      masking stimulus. The system is composed of an electronic shutter (a liquid
      crystal smart window) for exposing the stimulus scene, and a liquid crystal
      projector coupled with an electromechanical shutter for presenting the masking
      stimulus. This system can be used in both full- and reduced-cue viewing
      conditions, under monocular and binocular viewing, and at distances limited only
      by the testing space. We describe a configuration that may be used for studying
      the microgenesis of visual space perception in the context of visually directed
      walking.

PMID- 19182131
TI  - ATC-lab(Advanced): an air traffic control simulator with realism and control.
AB  - ATC-lab(Advanced) is a new, publicly available air traffic control (ATC)
      simulation package that provides both realism and experimental control. ATC
      lab(Advanced) simulations are realistic to the extent that the display features
      (including aircraft performance) and the manner in which participants interact
      with the system are similar to those used in an operational environment.
      Experimental control allows researchers to standardize air traffic scenarios,
      control levels of realism, and isolate specific ATC tasks. Importantly, ATC
      lab(Advanced) also provides the programming control required to cost effectively
      adapt simulations to serve different research purposes without the need for
      technical support. In addition, ATC-lab(Advanced) includes a package for training
      participants and mathematical spreadsheets for designing air traffic events.
      Preliminary studies have demonstrated that ATC-lab(Advanced) is a flexible tool
      for applied and basic research.

PMID- 19182132
TI  - ConceptBuilder: an open-source software tool for measuring, depicting, and
      quantifying causal models.
AB  - Measurements of people's causal and explanatory models are frequently key
      dependent variables in investigations of concepts and categories, lay theories,
      and health behaviors. A variety of challenges are inherent in the pen-and-paper
      and narrative methods commonly used to measure such causal models. We have
      attempted to alleviate these difficulties by developing a software tool,
      ConceptBuilder, for automating the process and ensuring accurate coding and
      quantification of the data. In this article, we present ConceptBuilder, a
      multiple-use tool for data gathering, data entry, and diagram display. We
      describe the program's controls, report the results of a usability test of the
      program, and discuss some technical aspects of the program. We also describe
      ConceptAnalysis, a companion program for generating data matrices and analyses,
      and ConceptViewer, a program for viewing the data exactly as drawn.

PMID- 19182133
TI  - Observer agreement for timed-event sequential data: a comparison of time-based
      and event-based algorithms.
AB  - Observer agreement is often regarded as the sine qua non of observational
      research. Cohen's kappa is a widely used index and is appropriate when discrete
      entities-such as a turn-of-talk or a demarcated time interval-are presented to
      pairs of observers to code. kappa-like statistics and agreement matrices are also
      used for the timed-event sequential data produced when observers first segment
      and then code events detected in the stream of behavior, noting onset and offset
      times. Such kappas are of two kinds: time-based and event-based. Available for
      download is a computer program (OASTES; Observer Agreement for Simulated Timed
      Event Sequences) that simulates the coding of observers of a stated accuracy and
      then computes agreement statistics for two time-based kappas (with and without
      tolerance) and three event-based kappas (one implemented in The Observer, one in
      INTERACT, and one in GSEQ). On the basis of simulation results presented here,
      and due to the somewhat different information provided by each, the reporting of
      both a time-based and an event-based kappa is recommended.

PMID- 19182134
TI  - Automated gait analysis in the open-field test for laboratory mice.
AB  - In this article, an automated and accurate mouse observation method, based on a
      conventional test for motor function evaluation, is outlined. The proposed
      measurement technique was integrated in a regular open-field test, where the
      trajectory and locomotion of a free-moving mouse were measured simultaneously.
      The system setup consisted of a transparent cage and a camera placed below it
      with its lens pointing upward, allowing for images to be captured from underneath
      the cage while the mouse was walking on the transparent cage floor. Thus,
      additional information was obtained about the position of the limbs of the mice
      for gait reconstruction. In a first step, the camera was calibrated as soon as it
      was fixed in place. A linear calibration factor, relating distances in image
      coordinates to real-world dimensions, was determined. In a second step, the mouse
      was located and its body contour segmented from the image by subtracting a
      previously taken "background" image of the empty cage from the camera image. In a
      third step, the movement of the mouse was analyzed and its speed estimated from
      its location in the past few images. If the speed was above a 1-sec threshold,
      the mouse was recognized to be running, and the image was further processed for
      footprint recognition. In a fourth step, color filtering was applied within the
      recovered mouse region to measure the position of the mouse's paws, which were
      visible in the image as small pink spots. Paws that were detected at the same
      location in a number of subsequent images were kept as footprints-that is, paws
      in contact with the cage floor. The footprints were classified by their position
      relative to the mouse's outline as corresponding to the front left or right paw
      or the hind left or right paw. Finally, eight parameters were calculated from the
      footprint pattern to describe the locomotion of the mouse: right/left overlap,
      front/hind base, right/left front limb stride, and right/left hind limb stride.
      As an application, the system was tested using normal mice and mice displaying
      pentobarbital-induced ataxia. The footprint parameters measured using the
      proposed system showed differences of 10% to 20% between normal and ataxic mice.

PMID- 19182135
TI  - ChoiceKey: a real-time speech recognition program for psychology experiments with
      a small response set.
AB  - Psychological experiments often collect choice responses using buttonpresses.
      However, spoken responses are useful in many cases-for example, when working with
      special clinical populations, or when a paradigm demands vocalization, or when
      accurate response time measurements are desired. In these cases, spoken responses
      are typically collected using a voice key, which usually involves manual coding
      by experimenters in a tedious and error-prone manner. We describe ChoiceKey, an
      open-source speech recognition package for MATLAB. It can be optimized by
      training for small response sets and different speakers. We show ChoiceKey to be
      reliable with minimal training for most participants in experiments with two
      different responses. Problems presented by individual differences, and occasional
      atypical responses, are examined, and extensions to larger response sets are
      explored. The ChoiceKey source files and instructions may be downloaded as
      supplemental materials for this article from brm.psychonomic
      journals.org/content/supplemental.

PMID- 19182136
TI  - The maze task: measuring forced incremental sentence processing time.
AB  - The maze task is an online measure of sentence processing time that provides an
      alternative to the standard moving window version of self-paced reading. Rather
      than each word of the sentence being presented in succession, two words are
      presented at the same time, and the participant must choose which word is a
      grammatical continuation of the sentence. This procedure forces the reader into
      an incremental mode of processing in which each word must be fully integrated
      with the preceding context before the next word can be considered. Previous
      research with this technique has not considered whether it is sufficiently
      sensitive to syntactic complexity effects or to garden path effects. Four
      experiments are reported demonstrating that reliable differences in processing
      time for subject relatives and object relatives can be obtained, and that this
      technique generates garden path effects that correspond closely with the data
      from eyetracking experiments, but without the spillover effects that are
      sometimes obtained with eyetracking. It is also shown that the task is sensitive
      to word frequency effects, producing estimates well in excess of those found with
      eyetracking.

PMID- 19182137
TI  - A new set of 84 colored nonobjects.
AB  - In this article, we present 84 nonobjects we created by using the colored object
      pictures from Rossion and Pourtois (2004). These nonobjects were explored on a
      number of measures, including object resemblance, visual complexity, and an
      object decision task (ODT). Object resemblance for nonobjects is a construct
      comparable to the "word-likeness" of phonotactically legal pseudowords. The
      nonobjects were rated as possible objects, showing similarity to real objects.
      Visual complexity ratings for objects and nonobjects were comparable. In the ODT,
      response times (RTs) were significantly longer for nonobjects than for real
      object pictures. This RT difference is analogous to the word advantage, or
      lexicality effect, found in lexical decision tasks, in which responses for words
      are generally faster than those for nonwords. This nonobject set is freely
      available and has the advantage of having a companion set of real-object
      pictures. The nonobjects are available in color and in grayscale from
      brm.psychonomic-journals.org/content/supplemental.

PMID- 19182138
TI  - Using UnGraph to extract data from image files: verification of reliability and
      validity.
AB  - Certain research tasks require extracting data points from graphs and charts.
      Using 91 graphs that presented results from single-case designs, we investigated
      whether pairs of coders extract similar data from the same graphs (reliability),
      and whether the extracted data match numerical descriptions of the graph that the
      original author may have presented in tables or text (validity). Coders extracted
      data using the UnGraph computer program. Extraction proved highly reliable over
      several different kinds of analyses. Coders nearly always extracted identical
      numbers of data points, and the values they assigned to those data points were
      nearly identical. Extraction also proved highly valid, with the means of
      extracted data correlating nearly perfectly with means reported in tables or text
      and with very few discrepancies in any single case. These results suggest that
      researchers can use extracted data with a high degree of confidence that they are
      nearly identical to the original data.

PMID- 19182139
TI  - Reaction time normative data for the IAPS as a function of display time, gender,
      and picture content.
AB  - This study aimed to extend the International Affective Picture System (IAPS;
      Lang, Bradley, & Cuthbert, 2005) norms by obtaining reaction time (RT) normative
      data for 308 selected photographs. Pictures were presented one at a time for 33,
      100, or 250 msec, or under free-time display, to 96 women and 48 men. The
      participants' task involved assessing the emotional valence of each picture and
      responding as quickly as possible as to whether it was unpleasant, neutral, or
      pleasant. RTs provided an index of processing efficiency. The manipulation of
      display time served to estimate the time course in the valence identification of
      each picture. Some categories of depicted scenes (e.g., erotica and mutilations)
      were classified more consistently and efficiently than were others as pleasant or
      unpleasant. There were minimal differences between men and women. Overall, the
      present data provide researchers investigating cognition/emotion relationships
      with an objective criterion to select pictorial stimuli on the basis of RTs. Data
      for all pictures may be downloaded from brm.psychonomic
      journals.org/content/supplemental.

PMID- 19182140
TI  - Design efficiency for imbalanced multilevel data.
AB  - The importance of accurate estimation and of powerful statistical tests is widely
      recognized but has rarely been acknowledged in practice in the social and
      behavioral sciences. This is especially true for estimation and testing when one
      is dealing with multilevel designs, not least because approximating accuracy and
      power is more complex due to having multiple variances and research units at
      several levels. The complexity further increases for imbalanced designs, often
      necessitating simulation studies that perform accuracy and power calculations.
      However, we show, using such simulation studies, that the distortion of balance
      can be ignored in most cases, making efficiency studies simpler and the use of
      existing software valid. An exception is suggested for imbalanced data from a
      large majority of small groups. Furthermore, an empirical sampling distribution
      of variance parameters may show substantial skewness and kurtosis, depending on
      the number of groups and, for the random slope, depending also on the group's
      size, adding another caveat to the recommendation to ignore imbalance.

PMID- 19182141
TI  - A laboratory-based procedure for measuring emotional expression from natural
      speech.
AB  - Despite dramatic advances in the sophistication of tools for measuring prosodic
      and content channels of expression from natural speech, methodological issues
      have limited the simultaneous measurement of those channels for laboratory
      research. This is particularly unfortunate, considering the importance of
      emotional expression in daily living and how it can be disrupted in many
      psychological disorders (e.g., schizophrenia). The present study examined the
      Computerized assessment of Affect from Natural Speech (CANS), a laboratory-based
      procedure that was designed to measure both lexical and prosodic expression from
      natural speech across a range of evocative conditions. The verbal responses of 38
      male and 31 female subjects were digitally recorded as they reacted to separate
      pleasant, unpleasant, and neutral stimuli. Lexical and prosodic expression
      variables significantly changed across these conditions, providing support for
      using the CANS in further laboratory research. The implications for understanding
      the interface between lexical and prosodic expressions are also discussed.

PMID- 19182142
TI  - Children's emotional norms for 600 French words.
AB  - The present study provides a French child database containing a large corpus of
      words (N = 600) that were rated on emotional valence (positive, neutral, and
      negative) by French children differing in both age (5, 7, and 9 years old) and
      sex (girls and boys). Good response reliability was observed in each of the three
      age groups. The results showed some age differences in the children's ratings.
      With increasing age, the percentage of words rated positive decreased, whereas
      the percentage of neutral words increased and the percentage of negative words
      remained stable. Our study did not reveal marked differences across sex groups.
      The database compiled here should become a useful tool for experimental studies
      in which verbal material is used with children. It would be worthwhile in future
      research to study how children process emotional words and also to control the
      emotional variable in the same way as other linguistic variables in the
      experimental design. The norms from this study may be downloaded from
      brm.psychonomic-journals.org/content/supplemental.

PMID- 19182143
TI  - Feedforward, -backward, and neutral transparency measures for British English.
AB  - Orthographic transparency metrics for opaque or deep languages, such as French
      and English, have tended to focus on feedforward and/or feedback directions, with
      claims made for the influence of both on reading. In the present study, data for
      five transparency metrics for southern British English, three of which are
      neither feedforward nor feedback, are presented, demonstrating the complex
      relationships between the metrics and offering an explanation for feedback
      effects in children's reading accuracy. The structure of such metrics from a
      variety of corpus sizes and origins is investigated, and it is concluded that
      large corpus sizes do not make a substantial contribution to the value of such
      metrics, when compared with smaller samples, and that adult and child corpuses
      have very similar profiles. Probabilities of occurrence for the phonemes,
      graphemes, and sonographs in this study may be downloaded from brm.psychonomic
      journals.org/content/supplemental.

PMID- 19182144
TI  - A video multitracking system for quantification of individual behavior in a large
      fish shoal: advantages and limits.
AB  - The capability of a new multitracking system to track a large number of unmarked
      fish (up to 100) is evaluated. This system extrapolates a trajectory from each
      individual and analyzes recorded sequences that are several minutes long. This
      system is very efficient in statistical individual tracking, where the
      individual's identity is important for a short period of time in comparison with
      the duration of the track. Individual identification is typically greater than
      99%. Identification is largely efficient (more than 99%) when the fish images do
      not cross the image of a neighbor fish. When the images of two fish merge
      (occlusion), we consider that the spot on the screen has a double identity.
      Consequently, there are no identification errors during occlusions, even though
      the measurement of the positions of each individual is imprecise. When the images
      of these two merged fish separate (separation), individual identification errors
      are more frequent, but their effect is very low in statistical individual
      tracking. On the other hand, in complete individual tracking, where individual
      fish identity is important for the entire trajectory, each identification error
      invalidates the results. In such cases, the experimenter must observe whether the
      program assigns the correct identification, and, when an error is made, must edit
      the results. This work is not too costly in time because it is limited to the
      separation events, accounting for fewer than 0.1% of individual identifications.
      Consequently, in both statistical and rigorous individual tracking, this system
      allows the experimenter to gain time by measuring the individual position
      automatically. It can also analyze the structural and dynamic properties of an
      animal group with a very large sample, with precision and sampling that are
      impossible to obtain with manual measures.

PMID- 19182145
TI  - Translation and validation of the Body Image Avoidance Questionnaire (BIAQ) for
      the Portuguese language in Brazil.
AB  - Brazilian researchers have not been provided with instruments with which to
      investigate body image avoidance behaviors. The aim of this study was to
      translate and validate the Body Image Avoidance Questionnaire (BIAQ) for Brazil.
      The translation, synthesis, back-translation, Brazilian questionnaire
      formulation, and pretest were carried out in the first phase of the study. The
      study of the scale's psychometric properties was conducted in the second phase of
      the study. Brazilian BIAQ has 13 items and good adjustment indexes. There was a
      greater adherence to the sampling data in the model in which the avoidance of
      body image is maintained by control strategies, by the refusal of body exposure,
      and by strategies that accommodate tension. This work is expected to enable the
      comparison of international data and the performance of multicultural studies on
      body avoidance behavior, expanding research possibilities in Brazil and
      worldwide.

PMID- 19182146
TI  - Evaluation of the relationship between one's differentiation of cognitive
      processes and metacognitive self-ratings.
AB  - It is questionable whether people can provide accurate and credible metacognitive
      self-evaluations. This study examined the relationship between metacognitive self
      assessment and the representation of cognitive processes. Fifty-four college
      students submitted written descriptions of different cognitive processes. Latent
      semantic analysis evaluated the descriptions with regard to each individual's
      differentiation among different processes at three stages: conditions, mental
      operations, and outcomes. Findings indicated that individuals with good self
      ratings differentiated different processes consistently at all three stages,
      whereas those with poor metacognitive self-ratings made clear distinctions
      between different processes in terms of conditions or outcomes of the processes,
      but much less so in terms of how the processes develop. The complex relationship
      between metacognitive self-perception and one's conceptual knowledge in this
      domain is discussed.

PMID- 19182149
TI  - Health care costs and utilization rates for children with pervasive developmental
      disorders in North Dakota from 1998 to 2004: impact on Medicaid.
AB  - In this study, we used data from the North Dakota Medicaid claims database from
      1998 through 2004 to estimate health care utilization rates and cost of care for
      children with pervasive developmental disorders. From the dataset, we developed a
      group comprised of children with pervasive developmental disorders (n = 546) and
      2 comparison groups: children with other mental disorders (n = 18 363) and
      children who did not have pervasive developmental disorders or any mental
      disorders (n = 63 202). Participants with pervasive developmental disorders
      utilized 4.6% of all visits and 5% of the total cost of health care over the 7
      year period. The average annual cost of care for children with pervasive
      developmental disorders was much higher than the cost for children without mental
      disorders for outpatient services ($5051 vs $360, ratio = 14:1), inpatient
      services ($1585 vs $458, ratio = 3.4:1), and pharmacy services ($1258 vs $82,
      ratio = 15:1). Children with pervasive developmental disorders covered by
      Medicaid have increased costs of health care.

PMID- 19182148
TI  - Identification of p53 as a strong predictor of survival for patients with
      malignant peripheral nerve sheath tumors.
AB  - The purpose of this study was to identify new prognostic biomarkers with clinical
      impact in malignant peripheral nerve sheath tumor (MPNST), a highly aggressive
      malignancy for which no consensus therapy exists besides surgery. We have used
      tissue microarrays (TMAs) to assess in situ expression of 14 cell-cycle
      regulating proteins in 64 well-characterized MPNST patients: 36 sporadic and 28
      with neurofibromatosis type 1 (NF1). We developed a new software application for
      evaluation and logistics of the TMA images and performed a literature survey of
      cell cycle proteins in MPNST. For NF1-associated patients, there was a clear
      association between nuclear expression of p53 and poor survival (p = 0.004).
      Among the other proteins analyzed, we also found significant associations between
      survival and clinical variables, but none were as strong as that for p53. For the
      total series of MPNSTs, p53 was shown to be an independent predictor of survival,
      and patients without remission, with tumor size larger than 8 cm, and with
      positive p53 expression had a 60 times greater risk of dying within the first 5
      years compared with the remaining patients (p = 0.000002). This is the most
      comprehensive study of in situ protein expression in MPNST so far, and expressed
      p53 was found to be a strong surrogate marker for outcome. Patients in complete
      remission with a primary p53-positive MPNST diagnosis may be considered in a high
      risk subgroup and candidates for adjuvant treatment.

PMID- 19182150
TI  - Neonatal seizures: treatment and treatment variability in 31 United States
      pediatric hospitals.
AB  - Neonatal seizures are one of the most common neurological disorders in infants.
      However, the optimal treatment strategy for neonatal seizures remains
      controversial and there is little data regarding current treatment of neonatal
      seizures. In this study we describe the current treatment of neonatal seizures
      and variation in practice among 31 pediatric hospitals in the United States. We
      retrospectively identified 6099 infants hospitalized in the first month of life
      in one of 31 pediatric hospitals participating in the Pediatric Health
      Information System, with a discharge diagnosis of seizure. As expected, most
      treated infants received phenobarbital. However, there was significant
      interhospital variability for all treatments studied including any antiepileptic
      drug treatment, phenytoin treatment, antiepileptic drug treatment through
      discharge, number of antiepileptic drugs used, and treatment with pyridoxine (P <
      .001). These findings highlight the need for rigorous controlled outcome studies
      to determine optimal therapy for neonatal seizures and devise treatment
      standards.

PMID- 19182151
TI  - The neurology of benign paroxysmal torticollis of infancy: report of 10 new cases
      and review of the literature.
AB  - Benign paroxysmal torticollis is an under-recognized cause of torticollis of
      early infancy. The attacks usually last for less than 1 week, recur from every
      few days to every few months, improve by age 2 years, and end by age 3. There
      very frequently is a family history of migraine. We did a detailed analysis of 10
      cases of benign paroxysmal torticollis, seen over 5 years, and compared our
      findings with those in the 103 cases in the literature. Detailed
      neurodevelopmental assessments, available only in our cases, showed accompanying
      gross motor delays in 5/10 children, with additional fine motor delays in 3/5. As
      the benign paroxysmal torticollis improved, so did the gross motor delays in 3/5,
      and the fine motor delays in 1/3. In all of our cases, at least 2 other family
      members had migraine. Benign paroxysmal torticollis is likely an age-sensitive,
      migraine-related disorder, commonly accompanied by delayed motor development.

PMID- 19182152
TI  - Visual fixation in Chiari type II malformation.
AB  - Chiari type II malformation is a congenital deformity of the hindbrain. Square
      wave jerks are horizontal involuntary saccades that interrupt fixation.
      Cerebellar disorders may be associated with frequent square wave jerks or
      saccadic oscillations such as ocular flutter. The effects of Chiari type II
      malformation on visual fixation are unknown. We recorded eye movements using an
      eye tracker in 21 participants with Chiari type II malformation, aged 8 to 19
      years while they fixated a target for 1 minute. Thirty-eight age-matched healthy
      participants served as controls. Square wave jerks' parameters were similar in
      the 2 groups. Saccadic oscillations were not seen. Chiari type II malformation is
      not associated with pathological square wave jerks or abnormal saccadic
      oscillations. The congenital nature of this deformity may permit compensation
      that preserves stable visual fixation. Alternatively, the deformity of Chiari
      type II malformation may spare parts of the cerebellum that usually cause
      fixation instability when damaged.

PMID- 19182153
TI  - Recovery of vision after adjuvant thalidomide in a child with tuberculous
      meningitis and acute lymphoblastic leukemia.
AB  - A 7-year-old child, on maintenance chemotherapy for acute lymphoblastic leukemia,
      developed tuberculous meningitis complicated by progressive basal meningeal
      inflammation and abscess formation, in spite of adequate tuberculosis treatment
      and adjunctive corticosteriod therapy. The child became blind as a result of
      involvement of the optic chiasm. After 2 months of adjunctive thalidomide
      therapy, the child regained vision and cranial magnetic resonance imaging showed
      marked reduction of the inflammatory changes previously demonstrated. Progression
      of intracranial tuberculous infection, in spite of a treatment that is generally
      considered to be adequate, is well recognized. Previous reports of a possible
      beneficiary role of thalidomide in these cases support an immunological basis.
      The present case suggests a role for thalidomide in the treatment of blindness
      due to involvement of the optic chiasm in progressive basal tuberculous
      meningitis.

PMID- 19182154
TI  - Tourette syndrome and comorbid pervasive developmental disorders.
AB  - We examined the rates of comorbid pervasive developmental disorders in
      participants with Tourette syndrome. We used 7288 participants from the Tourette
      Syndrome International Database Consortium Registry. We found 334 (4.6%; 1 of
      every 22 participants) with Tourette syndrome had a comorbid pervasive
      developmental disorder. In participants with Tourette syndrome and comorbid
      pervasive developmental disorders, 98.8% had one or more comorbidities (pervasive
      developmental disorder was not counted) compared to 13.2% in the group of
      participants with Tourette syndrome only. Variables from logistic modeling that
      were significant predictors of Tourette syndrome and pervasive developmental
      disorders were: male gender; no family history of tics/Tourette syndrome; and an
      increased number of comorbidities (P < .001). We found rates of comorbid Tourette
      syndrome and pervasive developmental disorders to be increased by 13 times.
      Identification of differences between subgroups of patients with Tourette
      syndrome may increase understanding of syndromal susceptibility, severity, and
      outcome.

PMID- 19182155
TI  - Pilot study on trihexyphenidyl in the treatment of dystonia in children with
      cerebral palsy.
AB  - The aim of this study was to assess trihexyphenidyl in reducing overall dystonia,
      improving upper limb function, and achieving goals in children with dystonic
      cerebral palsy. A randomized, double-blinded, placebo-controlled, crossover trial
      was conducted with 16 participants at a tertiary children's hospital. Assessments
      were performed at baseline, week 12, and week 28. The primary outcome measure was
      the Barry-Albright Dystonia scale for global assessment of dystonia. Secondary
      measures included the Quality of Upper Extremity Skills Test, Canadian
      Occupational Performance Measure, and Goal Attainment Scale. A total of 14
      children (88%) completed the study. Mean baseline Barry-Albright Dystonia score
      was 18.4 (95% confidence interval, 15.5-21.2). There were no significant
      treatment effects as measured by change in outcome scores. There were significant
      order effects for both the Goal Attainment Scale and performance aspect of the
      Canadian Occupational Performance Measure. Side effects were common. Larger
      experimental trials with more narrowly defined functional levels are indicated.

PMID- 19182156
TI  - Regional expression of dopamine D1 and D2 receptor proteins in the cerebral
      cortex of asphyxic newborn infants.
AB  - Dopamine D(1) and D(2) receptor protein expression was examined by Western
      blotting in newborn infants dying from cerebral asphyxia between 31 and 42 weeks'
      gestation, and matched controls. Frontal, occipital, temporal, and motor cortex
      tissue samples were obtained at autopsy (median postmortem interval 35 hours) and
      frozen for storage at -80 degrees C. A total of 2 immunoreactive bands were
      detected with each primary antibody in infant brain, whereas a single band was
      present in adult human and rat tissue. Immunoreactivity varied between cortical
      areas for both receptors, but their regional patterns differed significantly.
      D(1) protein levels were higher in motor and temporal cortex than in frontal or
      occipital cortex. D(2) protein showed graded expression frontal > motor >
      occipital > temporal cortex. Asphyxia cases showed lower expression of the upper
      D(2) immunoreactive band, but no difference in regional pattern. Lower D(2)
      receptor expression may attenuate stress responses and underlie increased
      vulnerability to hypoxia at birth.

PMID- 19182158
TI  - A male phenotype with Aicardi syndrome.
AB  - Aicardi syndrome is a rare neurodevelopmental condition that occurs almost
      exclusively in women. We report a second male phenotype and 47,XXY karyotype with
      a typical presentation of the Aicardi syndrome including a midline arachnoid
      cyst.

PMID- 19182157
TI  - Pediatric stroke in the United States and the impact of risk factors.
AB  - One approach to studying pediatric stroke is to analyze a national database that
      contains data on a significant number of children. We examined an administrative
      dataset of hospital discharges from the United States, Kids' Inpatient Database
      2003 (KID2003), for ICD-9 codes associated with hemorrhagic or ischemic stroke in
      children aged >30 days to 20 years. 3156 children were discharged with a
      diagnosis of ischemic stroke and 2022 with hemorrhagic stroke after statistical
      weighting. The odds for a male discharged with hemorrhagic stroke was 1.5 (CI:
      1.35-1.68) and for ischemic stroke was 1.37 (CI: 1.24-1.51) compared with a
      female. The odds for males discharged with a stroke were greatest for ages 16 to
      20 years and least for 4 years. This study confirms a male predominance for
      stroke. The odds for hospitalization with a stroke diagnosis are greatest in very
      young and older adolescent males. Hemorrhage is an important stroke subtype in
      children.

PMID- 19182159
TI  - Rupture of intracranial arterial aneurysms in neonates: case report and review of
      the literature.
AB  - The rupture of cerebral arterial aneurysm is an extremely rare cause of
      intracranial hemorrhage in infants. Brain magnetic resonance imaging is an
      excellent technique commonly used to suggest the diagnosis. In this article, we
      propose color flow Doppler ultrasound as a useful, simple, inexpensive,
      noninvasive, and accessible option for confirming the lesion.We report one case
      of cerebral aneurysm in a neonate admitted to our unit. Furthermore, we performed
      a thorough review of the literature on cerebral aneurysm that led us to the
      observation that the vast majority of untreated patients suffered a second
      bleeding that caused death. Thus, we insist on the benefits of a timely
      treatment.

PMID- 19182160
TI  - Successful treatment of cytomegalovirus polyradiculopathy in a 9-year-old child
      with congenital human immunodeficiency virus infection.
AB  - Cytomegalovirus lumbosacral polyradiculopathy is a well-documented complication
      of human immunodeficiency virus in adults who have a CD4 count of less than
      40/microL. Patients present with an acute ascending flaccid paralysis of the
      lower limbs with areflexia, paresthesia, and urinary and bowel symptoms. However,
      it appears to be rare in children with congenitally acquired immune deficiency
      syndrome. We report a 9-year-old child with congenital human immunodeficiency
      virus infection who presented with cytomegalovirus polyradiculopathy and made an
      excellent response to cytomegalovirus treatment.

PMID- 19182161
TI  - Bilateral paramedian thalamic and mesencephalic infarcts in a newborn due to
      occlusion of the artery of Percheron.
AB  - Bilateral paramedian thalamic and mesencephalic infarcts are infrequently
      reported in adults, and to our knowledge, has never been reported in a child. The
      presumed etiology is an occlusion of the artery of Percheron, an uncommon
      vascular variation, in which a single common trunk from one of the P1 segments of
      the posterior cerebral artery provides bilateral irrigation to the paramedian
      thalami and midbrain. Bilateral paramedian thalamic and mesencephalic infarcts in
      adults are associated with symptoms of decreased arousal, vertical gaze paresis,
      mood changes, and memory difficulties. Although some improvement of these
      symptoms does occur, complete recovery is rare. We present here a full-term male
      neonate, whose right-hand sided clonic seizures on day-of-life 2 prompted
      neuroimaging, which revealed bilateral paramedian thalamic and mesencephalic
      infarcts, suggestive of an occlusion of the artery of Percheron.

PMID- 19182162
TI  - Multiple congenital anomalies/mental retardation syndrome with multiple
      circumferential skin creases: a new syndrome?
AB  - We describe a combination of multiple congenital anomalies, a severe psychomotor
      retardation and seizures in a 9-year-old Tunisian boy with circumferential ringed
      skin creases. He had symmetrical circumferential skin creases on arms, legs, and
      penis. Craniofacial anomalies included: an elongated face, tight forehead,
      hypertelorism, bilateral epicanthic folds, upslanting palpebral fissures,
      microphthalmia, convergent strabismus, wide nasal bridge, aberrant teeth, dental
      caries, and low-set posteriorly rotated ears with overfolded thick helices. He
      had also ureterocele, hypospadias, and others anomalies. The magnetic resonance
      imaging of the brain showed hypoplastic vermis, hypoplastic corpus callosum, and
      dilatation of ventricles. Chromosomal analysis revealed a normal male karyotype
      with 46,XY. Skin biopsy was normal. To the best of our knowledge, this
      combination of anomalies has not been reported and this case may be a unique
      syndrome.

PMID- 19182163
TI  - Ictal vomiting as an initial symptom of severe myoclonic epilepsy in infancy: a
      case report.
AB  - We report on 3-year-old Japanese twin brothers suffering from ictal vomiting
      during infancy. Intractable seizures, including generalized tonic-clonic
      convulsions, and myoclonic seizures persisted in late infancy. The diagnosis of
      severe myoclonic epilepsy in infancy was confirmed by detecting a mutation in the
      voltage-gated sodium channel alpha subunit type gene. This is the first case
      report addressing ictal vomiting as the initial presentation of severe myoclonic
      epilepsy in infancy.

PMID- 19182164
TI  - Receptive language organization in high-functioning autism.
AB  - One of the core defining components of autism is impairment in communication,
      typically manifested as a delay in speech development. To date, neuroimaging
      studies have shed limited light on the mechanisms behind delay in speech
      development in autism. We performed magnetoencephalographic-based auditory
      language mapping in 2 cases of high-functioning autism. Overall, 2 distinct
      characteristics were found, such as the use of atypical language pathways and
      cortical hyperexcitability. These neurophysiological findings parallel those
      reported in 2 other developmental disorders, developmental dyslexia and Rett
      syndrome. We discuss common mechanisms that may account for cognitive delays
      across these developmental disorders.

PMID- 19182165
TI  - Determination of basal metabolic rate and body composition with bioelectrical
      impedance method in children with cerebral palsy.
AB  - This study uses the bioelectrical impedance method to assess the body
      composition, basal metabolic rate, and some other physical properties of children
      with cerebral palsy. In this study, 41 children with spastic cerebral palsy were
      assessed, and 56 normally developed children were included as control. Parameters
      such as body compositions, basal metabolic rate, body resistance, liquid
      compartment, and capacitance of patients and control group were measured and
      analyzed statistically. Basal metabolic rate, body mass index, extracellular
      liquid, intracellular liquid, body capacitance, and resistance differed
      significantly compared to the control group (P < .01), whereas extracellular
      mass, lean body mass, body cell mass, and fat mass did not differ significantly
      compared to the control group (P > .05). Parameters such as basal metabolic rate,
      body composition, and body resistance can be determined using the bioelectrical
      impedance method in children with cerebral palsy.

PMID- 19182166
TI  - Multiphasic acute disseminated encephalomyelitis or pediatric multiple sclerosis:
      report of an atypical case.
AB  - An international panel has recently proposed consensus definitions for pediatric
      multiple sclerosis and related disorders. These are important diagnostic
      improvements, but exceptions have been acknowledged. Further insight about
      clinical overlap between pediatric multiple sclerosis and all forms of relapsing
      acute disseminated encephalomyelitis may be gained from long-term follow-up. We
      report an 8-year follow-up of a girl who developed multiple episodes of central
      nervous system demyelination at the age of 3 years consistent with multiphasic
      acute disseminated encephalomyelitis. At 10 years of age (7 years after the first
      clinical event), she developed progressive cognitive deterioration, mood
      disorder, and headache, suggesting a secondary progressive form of multiple
      sclerosis. Magnetic resonance imaging and cerebrospinal fluid analysis were
      equivocal while visual evoked potentials were the sole test in favor of a
      diagnosis of multiple sclerosis. A multifaceted approach may be needed when
      dealing with atypical cases of demyelinating disease in young children.

PMID- 19182167
TI  - A salience dysregulation syndrome.
AB  - Revisions of DSM and ICD are forthcoming. Should the old categories of psychotic
      disorder, in particular the construct of schizophrenia, be retained or is a new
      system of representation of psychosis in order? It is argued that both scientific
      and societal developments point to a system of classification combining
      categorical and dimensional representations of psychosis in DSM and ICD.
      Furthermore, it is proposed to introduce, analogous to the functional descriptive
      term ;metabolic syndrome', the diagnosis of salience dysregulation syndrome.
      Within this syndrome, three sub-categories may be identified, based on scientific
      evidence of relatively valid and specific contrasts: with affective expression;
      with developmental expression; and not otherwise specified.

PMID- 19182168
TI  - Attitudes towards clinical services among people who self-harm: systematic
      review.
AB  - BACKGROUND: Self-harm is increasingly common in many countries, is often repeated
      and may have other negative outcomes. AIMS: To systematically review people's
      attitudes towards clinical services following self-harm in order to inform
      service design and improvement. METHOD: A search of electronic databases was
      conducted and experts in the field were contacted in order to identify relevant
      worldwide qualitative or quantitative studies. Data were extracted independently
      by two reviewers with more weight given to studies of greater quality and
      relevance. RESULTS: Thirty-one studies met the inclusion criteria. Despite
      variations in healthcare systems and setting, participants' experiences were
      remarkably similar. Poor communication between patients and staff and a perceived
      lack of staff knowledge with regard to self-harm were common themes. Many
      participants suggested that psychosocial assessments and access to after-care
      needed to be improved. CONCLUSIONS: Specific aspects of care that might increase
      service user satisfaction and treatment adherence include staff knowledge,
      communication and better after-care arrangements. A standard protocol could aid
      regular audits of users' experiences of services.

PMID- 19182169
TI  - Association of headache with childhood adversity and mental disorder: cross
      national study.
AB  - BACKGROUND: Community studies about the association of headache with both
      childhood family adversities and depression/anxiety disorders are limited. AIMS:
      To assess the independent and joint associations of childhood family adversities
      and early-onset depression and anxiety disorders with risks of adult-onset
      headache. METHOD: Data were pooled from cross-sectional community surveys
      conducted in ten Latin and North American, European and Asian countries (n=18
      303) by using standardised instruments. Headache and a range of childhood family
      adversities were assessed by self-report. RESULTS: The number of childhood family
      adversities was associated with adult-onset headache after adjusting for gender,
      age, country and early-onset depression/anxiety disorder status (for one
      adversity, hazard ratio (HR)=1.22-1.6; for two adversities, HR=1.19-1.67; for
      three or more adversities, HR=1.37-1.95). Early and current onset of
      depression/anxiety disorders were independently associated (HR=1.42-1.89) with
      adult-onset headache after controlling for number of childhood family
      adversities. CONCLUSIONS: The findings call for a broad developmental perspective
      concerning risk factors for development of headache.

PMID- 19182170
TI  - Look into my eyes.

PMID- 19182171
TI  - Comparative epidemiology of chronic fatigue syndrome in Brazilian and British
      primary care: prevalence and recognition.
AB  - BACKGROUND: Although fatigue is a ubiquitous symptom across countries, clinical
      descriptions of chronic fatigue syndrome have arisen from a limited number of
      high-income countries. This might reflect differences in true prevalence or
      clinical recognition influenced by sociocultural factors. AIMS: To compare the
      prevalence, physician recognition and diagnosis of chronic fatigue syndrome in
      London and Sao Paulo. METHOD: Primary care patients in London (n=2459) and Sao
      Paulo (n=3914) were surveyed for the prevalence of chronic fatigue syndrome.
      Medical records were reviewed for the physician recognition and diagnosis.
      RESULTS: The prevalence of chronic fatigue syndrome according to Centers for
      Disease Control 1994 criteria was comparable in Britain and Brazil: 2.1% v. 1.6%
      (P=0.20). Medical records review identified 11 diagnosed cases of chronic fatigue
      syndrome in Britain, but none in Brazil (P<0.001). CONCLUSIONS: The primary care
      prevalence of chronic fatigue syndrome was similar in two culturally and
      economically distinct nations. However, doctors are unlikely to recognise and
      label chronic fatigue syndrome as a discrete disorder in Brazil. The recognition
      of this illness rather than the illness itself may be culturally induced.

PMID- 19182173
TI  - Age-related grey matter volume correlates of response inhibition and shifting in
      attention-deficit hyperactivity disorder.
AB  - BACKGROUND: Children with attention-deficit hyperactivity disorder (ADHD) have
      difficulties with executive function and impulse control which may improve with
      age. AIMS: To map the brain correlates of executive function in ADHD and
      determine age-related changes in reaction times and brain volumes. METHOD:
      Attention-deficit hyperactivity disorder and control groups were compared on the
      change task measures of response inhibition (stop signal reaction time, SSRT) and
      shifting (change response reaction time, CRRT). Voxel-wise magnetic resonance
      imaging (MRI) correlations of reaction times and grey matter volume were
      determined, along with bivariate correlations of reaction times, brain volumes
      and age. RESULTS: Individuals in the ADHD group had longer SSRTs and CRRTs.
      Anterior cingulate, striatal and medial temporal volumes highly correlated with
      SSRT. Striatal and cerebellar volumes strongly correlated with CRRT. Older
      children had faster reaction times and larger regional brain volumes. In
      controls, orbitofrontal, medial temporal and cerebellar volumes correlated with
      CRRT but not SSRT. Neither reaction times nor regional brain volumes were
      strongly age-dependent. CONCLUSIONS: Our evidence supports delayed brain
      maturation in ADHD and implies that some features of ADHD improve with age.

PMID- 19182174
TI  - Structural and metabolic changes in language areas linked to formal thought
      disorder.
AB  - BACKGROUND: The role of the language network in the pathophysiology of formal
      thought disorder has yet to be elucidated. AIMS: To investigate whether specific
      grey-matter deficits in schizophrenic formal thought disorder correlate with
      resting perfusion in the left-sided language network. METHOD: We investigated 13
      right-handed patients with schizophrenia and formal thought disorder of varying
      severity and 13 matched healthy controls, using voxel-based morphometry and
      magnetic resonance imaging perfusion measurement (arterial spin labelling).
      RESULTS: We found positive correlations between perfusion and the severity of
      formal thought disorder in the left frontal and left temporoparietal language
      areas. We also observed bilateral deficits in grey-matter volume, positively
      correlated with the severity of thought disorder in temporoparietal areas and
      other brain regions. The results of the voxel-based morphometry and the arterial
      spin labelling measurements overlapped in the left posterior superior temporal
      gyrus and left angular gyrus. CONCLUSIONS: Specific grey-matter deficits may be a
      risk factor for state-related dysfunctions of the left-sided language system,
      leading to local hyperperfusion and formal thought disorder.

PMID- 19182175
TI  - Risk for depression and neural responses to fearful facial expressions of
      emotion.
AB  - BACKGROUND: Depression is associated with neural abnormalities in emotional
      processing. AIMS: This study explored whether these abnormalities underlie risk
      for depression. METHOD: We compared the neural responses of volunteers who were
      at high and low-risk for the development of depression (by virtue of high and low
      neuroticism scores; high-N group and low-N group respectively) during the
      presentation of fearful and happy faces using functional magnetic resonance
      imaging (fMRI). RESULTS: The high-N group demonstrated linear increases in
      response in the right fusiform gyrus and left middle temporal gyrus to
      expressions of increasing fear, whereas the low-N group demonstrated the opposite
      effect. The high-N group also displayed greater responses in the right amygdala,
      cerebellum, left middle frontal and bilateral parietal gyri to medium levels of
      fearful v. happy expressions. CONCLUSIONS: Risk for depression is associated with
      enhanced neural responses to fearful facial expressions similar to those observed
      in acute depression.

PMID- 19182176
TI  - Psychological processes in bipolar affective disorder: negative cognitive style
      and reward processing.
AB  - BACKGROUND: Psychological processes in bipolar disorder are of both clinical and
      theoretical importance. AIMS: To examine depressogenic psychological processes
      and reward responsivity in relation to different mood episodes (mania,
      depression, remission) and bipolar symptomatology. METHOD: One hundred and seven
      individuals with bipolar disorder (34 in a manic/hypomanic or mixed affective
      state; 30 in a depressed state and 43 who were euthymic) and 41 healthy controls
      were interviewed with Structured Clinical Interview for DSM-IV and completed a
      battery of self-rated and experimental measures assessing negative cognitive
      styles, coping response to negative affect, self-esteem stability and reward
      responsiveness. RESULTS: Individuals in all episodes differed from controls on
      most depression-related and reward responsivity measures. However, correlational
      analyses revealed clear relationships between negative cognitive styles and
      depressive symptoms, and reward responsivity and manic symptoms. CONCLUSIONS:
      Separate psychological processes are implicated in depression and mania, but
      cognitive vulnerability to depression is evident even in patients who are
      euthymic.

PMID- 19182177
TI  - Watching someone die.

PMID- 19182178
TI  - Cognitive-behavioural therapy v. social activity therapy for people with
      psychosis and a history of violence: randomised controlled trial.
AB  - BACKGROUND: Aggression and violence are serious problems in schizophrenia.
      Cognitive-behavioural therapy (CBT) has been shown to be an effective treatment
      for psychosis although there have been no studies to date evaluating the impact
      of CBT for people with psychosis and a history of violence. AIMS: To investigate
      the effectiveness of CBT on violence, anger, psychosis and risk outcomes with
      people who had a diagnosis of schizophrenia and a history of violence. METHOD:
      This was a single-blind randomised controlled trial of CBT v. social activity
      therapy (SAT) with a primary outcome of violence and secondary outcomes of anger,
      symptoms, functioning and risk. Outcomes were evaluated by masked assessors at 6
      and 12 months (trial registration: NRR NO50087441). RESULTS: Significant benefits
      were shown for CBT compared with control over the intervention and follow-up
      period on violence, delusions and risk management. CONCLUSIONS: Cognitive
      behavioural therapy targeted at psychosis and anger may be an effective treatment
      for reducing the occurrence of violence and further investigation of its benefits
      is warranted.

PMID- 19182179
TI  - Efficacy, safety and tolerability of two dosing regimens in adolescent
      schizophrenia: double-blind study.
AB  - BACKGROUND: Effective treatments for adolescent schizophrenia are needed. AIMS:
      To compare efficacy and safety of two dosing regimens of risperidone. METHOD:
      Double-blind, 8-week study. Patients, 13-17 years, with an acute episode of
      schizophrenia, randomised 1:1 to risperidone 1.5-6.0 mg/day (regimen A; n=125) or
      0.15-0.6 mg/day (regimen B; n=132). TRIAL REGISTRATION NUMBER: NCT00034749.
      RESULTS: Mean total Positive and Negative Syndrome Scale (PANSS) score improved
      significantly (P<0.001; effect size=0.49) from baseline to end-point for regimen
      A (mean=96.4 (s.d.=15.39) to mean=72.8 (s.d.=22.52)) compared with regimen B
      (mean=93.3 (s.d.=14.14) to mean=80.8 (s.d.=24.33)). Treatment-emergent adverse
      events occurred in 74% (regimen A) and 65% (regimen B) of patients; 4% of
      patients overall discontinued for adverse events. Mean change in body weight was
      3.2 kg (s.d.=3.49) for regimen A and 1.7 kg (s.d.=3.29) for regimen B.
      CONCLUSIONS: Adolescent patients in the regimen A group showed greater
      improvement in total PANSS compared with the regimen B group. Treatment was well
      tolerated.

PMID- 19182180
TI  - Reasons for discontinuing clozapine: matched, case-control comparison with
      risperidone long-acting injection.
AB  - BACKGROUND: Clozapine has a range of serious adverse effects that may give rise
      to an increased risk of death. AIMS: To compare reasons for discontinuation of
      clozapine with reasons for discontinuation of risperidone long-acting injection
      in age-matched individuals treated in the same clinical environment. METHOD:
      Comparison of patients receiving clozapine and an age-matched control group
      receiving risperidone injection. RESULTS: We established outcome for 529
      consecutive patients receiving clozapine and 250 receiving risperidone (161
      discontinuers from each group were compared). Adverse effects (odds ratio
      OR=2.19, 95% CI 1.31-3.67) and death (OR=7.0, 95% CI 2.09-23.5) were more
      commonly observed as reasons for discontinuation of clozapine than of
      risperidone. Clozapine was less likely to be withdrawn because of ineffectiveness
      than was risperidone (OR=0.034, 95% CI 0.01-0.14). Standardised mortality ratio
      (SMR) was significantly raised for patients receiving clozapine (SMR=4.17, 95% CI
      2.78-6.26). Pneumonia was the most common single cause of death. CONCLUSIONS:
      Clozapine use in patients with severe mental illness was associated with a
      significantly increased risk of death compared with that for the general
      population. Causation could not be established. Adverse effects and death are
      common causes of clozapine discontinuation.

PMID- 19182181
TI  - Adolescent-onset anorexia nervosa: 18-year outcome.
AB  - BACKGROUND: The long-term outcome of anorexia nervosa is insufficiently
      researched. AIMS: To study prospectively the long-term outcome and prognostic
      factors in a representative sample of people with teenage-onset anorexia nervosa.
      METHOD: Fifty-one people with anorexia nervosa, recruited by community screening
      and with a mean age at onset of 14 years were compared with 51 matched comparison
      individuals at a mean age of 32 years (18 years after disorder onset). All
      participants had been examined at ages 16 years, 21 years and 24 years. They were
      interviewed for Axis I psychiatric disorders and overall outcome (Morgan-Russell
      assessment schedule and the Global Assessment of Functioning). RESULTS: There
      were no deaths. Twelve per cent (n=6) had a persisting eating disorder, including
      three with anorexia nervosa. Thirty-nine per cent of the anorexia nervosa group
      met the criteria for at least one psychiatric disorder. The general outcome was
      poor in 12%. One in four did not have paid employment owing to psychiatric
      problems. Poor outcome was predicted by premorbid obsessive-compulsive
      personality disorder, age at onset of anorexia nervosa and autistic traits.
      CONCLUSIONS: The 18-year outcome of teenage-onset anorexia nervosa is favourable
      in respect of mortality and persisting eating disorder.

PMID- 19182182
TI  - Suicide in dementia: 9-year national clinical survey in England and Wales.
AB  - BACKGROUND: Knowledge of suicide in people with dementia is limited to small case
      series. AIMS: To describe behavioural, clinical and care characteristics of
      people with dementia who died by suicide. METHOD: All dementia cases (n=118) from
      a 9-year national clinical survey of suicides in England and Wales (n=11 512)
      were compared with age- and gender-matched non-dementia cases (control group)
      (n=492) by conditional logistic regression. RESULTS: The most common method of
      suicide in patients with dementia was self-poisoning, followed by drowning and
      hanging, the latter being less frequent than in controls. In contrast to
      controls, significantly fewer suicides occurred within 1 year of diagnosis in
      patients with dementia. Patients with dementia were also less likely to have a
      history of self-harm, psychiatric symptoms and previous psychiatric admissions.
      CONCLUSIONS: Known indicators of suicide risk are found less frequently in
      dementia suicide cases than non-dementia suicide cases. Further research should
      clarify whether suicide in dementia is a response to worsening dementia or an
      underappreciation of psychiatric symptoms by clinicians.

PMID- 19182183
TI  - Post-mortem recollections of a medical lecturer (1836), Charles Lever.

PMID- 19182184
TI  - Duration of untreated prodromal symptoms and 12-month functional outcome of
      individuals at risk of psychosis.
AB  - Individuals seeking help from prodromal services may have been experiencing
      attenuated psychotic features and psychosocial impairments for a long period
      prior to referral. The effect of an extended duration of these untreated ;at
      risk' symptoms on patients' long-term functional outcome was assessed in a 12
      month longitudinal observational study (n=49). A longer duration of untreated ;at
      risk' symptoms was correlated with a reduced improvement in Global Assessment of
      Functioning scores after 12 months (beta=-0.375, P=0.008). This effect was
      independent of age and gender and may have implications for the improvement of
      treatment strategies in pre-psychotic phases.

PMID- 19182185
TI  - Suicides in female prisoners in England and Wales, 1978-2004.
AB  - We calculated, in narrow age bands, suicide rates for female prisoners compared
      with the general population between 1978 and 2004. The standardised mortality
      ratio (SMR) for suicide was 20.7 (95% CI 16.7-25.7), with a higher excess in
      younger women (<25 years, SMR=40 (95% CI 29-57); >or=25 years, SMR=20 (95% CI 15
      26)). There was a trend over time for SMRs to have increased, supporting the need
      for recent national initiatives for suicide prevention in prisoners.

PMID- 19182186
TI  - Homicide due to mental disorder.

PMID- 19182187
TI  - Homicide due to mental disorder.

PMID- 19182188
TI  - Time to start taking an internet history?

PMID- 19182189
TI  - Antipsychotics and risk of diabetes in schizophrenia.

PMID- 19182191
TI  - Pharmacology and human morality.

PMID- 19182192
TI  - Pharmacology and human morality.

PMID- 19182194
TI  - Duration of untreated psychosis in LAMI countries.

PMID- 19182197
TI  - To prescribe or not to prescribe?

PMID- 19182199
TI  - Effects of an earthquake on suicide rates in Nantou, Taiwan.

PMID- 19182201
TI  - Increasing awareness of eGFR monitoring.

PMID- 19182202
TI  - Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree
      relatives of 4458 patients with monoclonal gammopathy of undetermined
      significance in Sweden.
AB  - Familial clustering of the precursor condition, monoclonal gammopathy of
      undetermined significance (MGUS) has been observed in case reports and in smaller
      studies. Using population-based data from Sweden, we identified 4458 MGUS
      patients, 17505 population-based controls, and first-degree relatives of patients
      (n = 14621) and controls (n = 58387) with the aim to assess risk of MGUS and
      lymphoproliferative malignancies among first-degree relatives of MGUS patients.
      Compared with relatives of controls, relatives of MGUS patients had increased
      risk of MGUS (relative risk [RR] = 2.8; 1.4-5.6), multiple myeloma (MM; RR = 2.9;
      1.9-4.3), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM; RR =
      4.0; 1.5-11), and chronic lymphocytic leukemia (CLL; RR = 2.0; 1.2-2.3).
      Relatives of patients with IgG/IgA MGUS had a 4.0-fold (1.7-9.2), 2.9-fold (1.7
      4.9), and 20-fold (2.3-170) elevated risk of developing MGUS, MM, and LPL/WM,
      respectively. Relatives of IgM MGUS patients had 5.0-fold (1.1-23) increased CLL
      risk and nonsignificant excess MM and LPL/WM risks. The results were very similar
      when we assessed risk by type of first-degree relative, age at MGUS (above/below
      65 years), or sex. Risk of non-Hodgkin lymphoma or Hodgkin lymphoma was not
      increased among MGUS relatives. Among first-degree relatives of a nationwide MGUS
      cohort, we found elevated risks of MGUS, MM, LPL/WM, and CLL, supporting a role
      for germline susceptibility genes, shared environmental influences, or an
      interaction between both.

PMID- 19182203
TI  - Depletion of CD4 T cells enhances immunotherapy for neuroblastoma after syngeneic
      HSCT but compromises development of antitumor immune memory.
AB  - High-risk neuroblastoma remains a clinically challenging disease. Here, we report
      that a multifaceted immunotherapeutic approach including syngeneic hematopoietic
      stem cell transplantation (HSCT), adoptive transfer of sensitized T cells (from
      syngeneic donors vaccinated to tumor antigens), and early posttransplantation
      tumor vaccination can effectively treat mice with established neuroblastoma.
      Vaccination was an important component of this immunotherapy, as it resulted in
      enhanced and prolonged tumor-specific CD8 T-cell activity and improved antitumor
      efficacy. Surprisingly, CD4 cell depletion of mice given sensitized T cells
      resulted in better tumor-free survival, which was associated with an early
      increased expansion of CD8 T cells with an effector phenotype, increased numbers
      of tumor-reactive CD8 T cells, and increased tumor infiltration by CD8 T cells.
      However, in the absence of CD4 T cells, development of long-term tumor immunity
      (memory) was severely compromised as reflected by diminished CD8 T-cell recall
      responses and an inability to resist tumor rechallenge in vivo. Based on these
      results, a major challenge with this immunotherapeutic approach is how to obtain
      the ideal initial antitumor response but still preserve antitumor immune memory.
      These data suggest that identification and selective depletion of immune
      inhibitory CD4 T cells may be a strategy to enhance early antitumor immunity and
      induce a long-lasting tumor response after HSCT.

PMID- 19182204
TI  - A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma:
      prospects for dual-targeted antibody/radioantibody therapy.
AB  - Antibody-based therapies, both unconjugated antibodies and radioimmunotherapy,
      have had a significant impact on the treatment of non-Hodgkin lymphoma. Single
      agent rituximab is an effective therapy, but it is being increasingly used with
      combination chemotherapy to improve the objective response and its duration. The
      approved anti-CD20 radioimmunoconjugates ((90)Y-ibritumomab tiuxetan or (131)I
      tositumomab) have had encouraging results, with trials now seeking to incorporate
      a radioimmunoconjugate in various settings. However, new preclinical data raise
      important questions concerning current radioimmunoconjugate treatment regimens
      and ways to improve them. In radioconjugate therapy, nearly 900 mg of the
      unlabeled anti-CD20 IgG antibody is predosed to the patient before the anti-CD20
      antibody conjugated to either (90)Y or (131)I is given. Combining an unconjugated
      anti-CD20 antibody therapy with a radioimmunoconjugate binding to a noncompeting
      antigen might improve responses by allowing optimal uptake of each agent.
      Preclinical models have indicated that careful consideration should be given to
      predosing when using competing antibodies, but that consolidation anti-CD20
      therapy enhances the efficacy of radioimmunoconjugate therapy. New technologies,
      such as pretargeted radioimmunotherapy, also hold promise by reducing toxicity
      without sacrificing efficacy, and consideration should be given to fractionating
      or giving multiple radioimmunoconjugate treatments. This perspective discusses
      how these issues could affect current and future clinical trials.

PMID- 19182205
TI  - Lenalidomide, adriamycin, and dexamethasone (RAD) in patients with relapsed and
      refractory multiple myeloma: a report from the German Myeloma Study Group DSMM
      (Deutsche Studiengruppe Multiples Myelom).
AB  - We conducted a phase 1/2 trial combining lenalidomide (R) with adriamycin (A) and
      dexamethasone (D) for relapsed and relapsed-refractory myeloma to determine
      tolerability and efficacy of this novel regimen, RAD, delivered for six 28-day
      cycles. A total of 69 intensively pretreated patients with a median age of 65
      years (range, 46-77 years) were enrolled. Using pegfilgrastim (G), the maximum
      tolerated dose (MTD) was formally not reached at the highest dose level (R, 25 mg
      on days 1-21; A, 9 mg/m(2) intravenously on days 1-4; and D, 40 mg on days 1-4
      and 17-20; dose level 5+G), which was then used to determine efficacy. Grades 3/4
      neutropenia and thrombocytopenia were seen in 48% and 38% of patients,
      respectively. Thromboembolic events occurred in 4.5% and severe infections in
      10.5% of patients. On an intent-to treat analysis, overall response rate (ORR)
      was 73% for the whole study and 77% including 74% complete response (CR) plus
      very good partial response (VGPR) for dose level 5+G. Response rates and
      progression-free survival did not differ between relapsed and relapsed-refractory
      patients. Deletion of chromosome 17p and elevated beta(2)-microglobulin were
      associated with significantly inferior response and shortened time to
      progression. In conclusion, RAD induces substantial and durable remission with an
      acceptable toxicity profile in patients with relapsed and relapsed-refractory
      myeloma. This trial was registered at www.ClinicalTrials.gov as no. NCT00306813.

PMID- 19182206
TI  - Enolase-1 promotes plasminogen-mediated recruitment of monocytes to the acutely
      inflamed lung.
AB  - Cell surface-associated proteolysis plays a crucial role in the migration of
      mononuclear phagocytes to sites of inflammation. The glycolytic enzyme enolase-1
      (ENO-1) binds plasminogen at the cell surface, enhancing local plasmin
      production. This study addressed the role played by ENO-1 in lipopolysaccharide
      (LPS)-driven chemokine-directed monocyte migration and matrix invasion in vitro,
      as well as recruitment of monocytes to the alveolar compartment in vivo. LPS
      rapidly up-regulated ENO-1 cell-surface expression on human blood monocytes and
      U937 cells due to protein translocation from cytosolic pools, which increased
      plasmin generation, enhanced monocyte migration through epithelial monolayers,
      and promoted matrix degradation. These effects were abrogated by antibodies
      directed against the plasminogen binding site of ENO-1. Overexpression of ENO-1
      in U937 cells increased their migratory and matrix-penetrating capacity, which
      was suppressed by overexpression of a truncated ENO-1 variant lacking the
      plasminogen binding site (ENO-1DeltaPLG). In vivo, intratracheal LPS application
      in mice promoted alveolar recruitment of monocytic cells that overexpressed ENO
      1, but not of cells overexpressing ENO-1DeltaPLG. Consistent with these data,
      pneumonia-patients exhibited increased ENO-1 cell-surface expression on blood
      monocytes and intense ENO-1 staining of mononuclear cells in the alveolar space.
      These data suggest an important mechanism of inflammatory cell invasion mediated
      by increased cell-surface expression of ENO-1.

PMID- 19182208
TI  - Deficiency of von Willebrand factor protects mice from ischemic stroke.
AB  - We recently demonstrated that blockade of the platelet adhesion receptor
      glycoprotein (GP) Ibalpha protects mice from ischemic stroke. Although von
      Willebrand factor (VWF) is the major ligand for GPIbalpha, GPIbalpha can engage
      other counterreceptors on endothelial cells, platelets, and leukocytes (eg, Mac-1
      or P-selectin) potentially involved in stroke outcome. To further analyze whether
      VWF is of particular relevance for stroke development, VWF(-/-) mice underwent 60
      minutes of middle cerebral artery occlusion. After 24 hours, VWF(-/-) mice had
      significantly smaller infarctions (P< .05) and less severe neurologic deficits
      (P< .01) compared with controls. This effect was sustained after 1 week, and
      intracranial bleeding was absent in VWF(-/-) mice as revealed by serial magnetic
      resonance imaging. Hydrodynamic injection of a VWF-encoding plasmid restored the
      susceptibility for stroke in VWF(-/-) mice. This study indicates that VWF is
      critically involved in cerebral ischemia. Hence, targeted inhibition of the
      GPIbalpha-VWF pathway might become a promising therapeutic option.

PMID- 19182207
TI  - Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong
      graft-versus-leukemia effects across MHC barriers in full chimeras.
AB  - Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL)
      effects but can also trigger life-threatening graft-versus-host disease (GVHD)
      after hematopoietic cell transplantation (HCT) across major histocompatibility
      complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can
      circumvent the need of recipient-derived APCs in vivo for mediating robust GVL
      effects and significantly diminishes the risk of severe GVHD. In vitro, generated
      and expanded T cells (ETCs) mediate anti-leukemia effects only when primed on
      recipient-derived APCs. Loading of APCs in vitro with leukemia cell lysate,
      chimerism status of the recipient, and timing of adoptive transfer after HCT are
      important factors determining the outcome. Delayed transfer of ETCs resulted in
      strong GVL effects in leukemia-bearing full chimera (FC) and mixed chimera (MC)
      recipients, which were comparable with the GVL/GVHD rates observed after the
      transfer of naive donor lymphocyte infusion (DLI). Upon early transfer, GVL
      effects were more pronounced with ETCs but at the expense of significant GVHD.
      The degree of GVHD was most severe in MCs after transfer of ETCs that had been in
      vitro primed either on nonpulsed recipient-derived APCs or with donor-derived
      APCs.

PMID- 19182209
TI  - Caspase-8 dependent histone acetylation by a novel proteasome inhibitor, NPI
      0052: a mechanism for synergy in leukemia cells.
AB  - Combination studies of histone deacetylase inhibitors (HDACi) and proteasome
      inhibitors are providing preclinical framework to build better strategies against
      hematologic malignancies. Our previous work found that a novel proteasome
      inhibitor, NPI-0052, and HDACi synergistically induce apoptosis in leukemia cells
      in a caspase-8- and oxidant-dependent manner. Here we extend those observations
      to primary leukemia cells and identify novel mechanisms of synergy. Because the
      proximal targets of NPI-0052 and HDACi are inhibition of proteasome activity and
      histone acetylation, we initially examined those biochemical events. Increased
      acetylation of histone-H3 was detected in Jurkat and CLL primary cells treated
      with NPI-0052, alone or in combination with various HDACi (MS/SNDX-275 or
      vorinostat). Hyperacetylation by NPI-0052 occurred to a lesser extent in caspase
      8-deficient cells and in cells treated with an antioxidant. These results
      indicate that NPI-0052 is eliciting caspase-8 and oxidative stress-dependent
      epigenetic alterations. In addition, real-time PCR revealed that MS/SNDX-275
      repressed expression of the proteasomal beta5, beta2, and beta1 subunits,
      consequently inhibiting respective enzymatic activities. Overall, our results
      suggest that crosstalk by NPI-0052 and HDACi are contributing, along with caspase
      8 activation and oxidative stress, to their synergistic cytotoxic effects in
      leukemia cells, reinforcing the potential clinical utility of combining these 2
      agents.

PMID- 19182210
TI  - Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in
      normal and tumoral human myelopoiesis.
AB  - Retinoids triggers differentiation of acute promyelocytic leukemia (APL) blasts
      by transcriptional regulation of myeloid regulatory genes. Using a microarray
      approach, we have identified a novel retinoid-responsive gene (CXXC5) encoding a
      nuclear factor, retinoid-inducible nuclear factor (RINF), that contains a CXXC
      type zinc-finger motif. RINF expression correlates with retinoid-induced
      differentiation of leukemic cells and with cytokine-induced myelopoiesis of
      normal CD34(+) progenitors. Furthermore, short hairpin RNA (shRNA) interference
      suggests for this gene a regulatory function in both normal and tumoral
      myelopoiesis. Interestingly, RINF localizes to 5q31.3, a small region often
      deleted in myeloid leukemia (acute myeloid leukemia [AML]/myelodysplasia [MDS])
      and suspected to harbor one or several tumor suppressor gene.

PMID- 19182211
TI  - A single nucleotide polymorphism in the promoter of the LOXL1 gene and its
      relationship to pelvic organ prolapse and preterm premature rupture of membranes.
AB  - Pelvic organ prolapse and preterm premature rupture of membranes, the 2
      conditions which have in common weakening of the tensile strength of tissues, are
      thought to be caused, in part, by abnormal extracellular matrix synthesis and/or
      catabolism. We identified a new single nucleotide polymorphism
      (NT_010194(LOXL1):g.45008784A>C) in the promoter of the LOXL1 gene, which is
      essential for elastin synthesis. Promoter studies showed that the minor "C''
      allele had significantly greater activity than the major "A'' allele. Case
      control studies examined the association of the alleles of this single nucleotide
      polymorphism with pelvic organ prolapse and preterm premature rupture of
      membranes. When comparing allele frequencies and genotypes in pelvic organ
      prolapse cases versus controls, no significant associations were found. A case
      control study conducted in African American neonates also found no significant
      associations between the promoter alleles and preterm premature rupture of
      membranes. We conclude that a functional single nucleotide polymorphism exists in
      the promoter region of the LOXL1 gene. Association studies suggest that the
      promoter single nucleotide polymorphism does not contribute significantly to risk
      of pelvic organ prolapse or preterm premature rupture of membranes.

PMID- 19182212
TI  - Seroprevalence of HIV/HBV coinfection in Malian blood donors.
AB  - OBJECTIVES: A cross-sectional study was conducted to assess the prevalence of
      human immunodeficiency virus (HIV), hepatitis B virus (HBV), and their
      coinfection among blood donors at the National Blood Transfusion Center in
      Bamako, Mali, from November 2001 to July 2002. METHODS: Enzyme-linked
      immunosorbent assay techniques with reagents from Bio-Rad (France) were used to
      test the blood samples. RESULTS: 11,592 blood donors were tested for HIV and HBV
      surface antigens. The prevalence of HIV was 4.5% and the prevalence of HBV was
      14.9%. The HIV/HBV coinfection rate was only 1.13% in this population.
      CONCLUSION: The coinfection rate was unexpectedly low in this blood donor
      population where monoinfection with HIV or HBV prevalence was high.

PMID- 19182213
TI  - Differential evaluation of excisional non-occluded wound healing in db/db mice.
AB  - The full-thickness wound in the genetically diabetic (db/db) mouse is a commonly
      used model of impaired wound healing. We investigated delayed healing of non
      occluded, excisional, full-thickness, dermal wounds in db/db mice in comparison
      to their normal littermate controls and refined methods for monitoring skin wound
      re-epithelialization, contraction, granulation tissue formation, and
      inflammation. We have confirmed with a computer-assisted planimetry method the
      results of previous studies showing that healing of non-occluded full excision
      wounds in db/db mice does not occur by contraction as much as in healthy mice. In
      addition, we have developed separate histological methods for the assessment of
      re-epithelialization, contraction, granulation tissue (mature, immature,
      fibrosis), and inflammation (lipogranulomas, secondary, nonspecific). Using a new
      approach to histological assessment, we have shown that wound closure in db/db
      mice is delayed owing to: (1) delayed granulation tissue maturation; (2)
      ''laced,'' widely distributed granulation tissue around fat lobules; and (3)
      obstruction by lipogranulomas, whereas the rate of re-epithelialization seems to
      be the same as in C57Bl/6 mice. This methodology should permit a more precise
      differentiation of effects of novel therapeutic agents on the wound healing
      process in db/db mice.

PMID- 19182214
TI  - The cost-effectiveness of screening for hereditary hemochromatosis in Germany: a
      remodeling study.
AB  - OBJECTIVE: Genetic tests for hereditary hemochromatosis (HH) are currently
      included in the German ambulatory care reimbursement scheme but only for
      symptomatic individuals and the offspring of HH patients. This study synthesizes
      the most current evidence to examine whether screening in the broader population
      is cost-effective and to identify the best choice of initial and follow-up
      screening tests. METHODS: A probabilistic decision-analytic model was constructed
      to calculate cost per life year gained (LYG) for HH screening among male
      Caucasians aged 30. Three strategies were considered in both the general
      population and male offspring of HH patients: phenotypic (transferrin saturation,
      TS), genotypic (C282Y mutation), and sequential (genotype if TS is elevated)
      screening. RESULTS: The incremental cost-effectiveness of sequential screening
      among male offspring, sequential population-wide screening, and genotypic
      screening is 41000, 124000, and 161000 Eero/LYG, respectively. All other
      strategies were subject to simple or extended dominance. The results are subject
      to high uncertainty. The most influential parameters in the deterministic one-way
      sensitivity analysis are discounting of life years gained and the adherence of
      patients to preventive phlebotomy. DISCUSSION: The current German policy of only
      screening at-risk individuals is consistent with health economic decision making
      based on typically accepted thresholds. However, conducting the DNA test after
      the first elevated TS result is more cost-effective than waiting for a second TS
      result as recommended by the German guidelines. Further empirical work regarding
      adherence to long-term prevention recommendations and explicit and well-justified
      guidance for the choice of discount rates in German economic evaluation are
      needed.

PMID- 19182215
TI  - Prospective evaluation of transition to specialized home palliative care in
      Japan.
AB  - The aim of this study was to clarify patients' characteristics and the level of
      symptom management in the transition to specialized home palliative care, and to
      examine prospectively real-time evaluation of both terminal cancer patients and
      their families. This study was conducted at one of the largest institutions
      offering specialized home palliative care in Japan. We asked both the patient's
      and the family's health status at the initial assessment and 2 weeks later. One
      hundred sets of patients and their families were included in this study.
      Regarding patient characteristics at the time of referral to the specialized home
      palliative care service, patients referred from outpatient settings had more
      severe physical symptoms than patients referred from inpatient settings. The
      specialized home palliative care service could contribute to patients' symptom
      and families' psychosocial status.

PMID- 19182216
TI  - ''How could you do this, doctor . . .?''.

PMID- 19182217
TI  - Bioelectrical impedance phase angle changes during hydration and prognosis in
      advanced cancer.
AB  - INTRODUCTION: We wished to determine bioelectrical impedance (BIA) correlates
      before hydration or changes during hydration and determine if these changes were
      prognostically important. METHODS AND MATERIALS: Fifty eligible patients
      underwent BIA measurements 3 consecutive days. Laboratory studies (electrolytes,
      creatinine, and hemoglobin) on day 1; weights and vital signs were recorded.
      Kaplan-Meier survival estimates were made at 30 and 60 days. Hazard ratios (HRs)
      based on Cox proportional hazards model were calculated. RESULTS: Weight loss was
      associated with shorter survival. A higher phase angle (PA) on day 1 predicted
      longer survival. Increased PA during hydration predicted shorter survival:
      increased weight during hydration predicted longer survival. DISCUSSION: Higher
      phase angle before hydration predicts poorer survival and, paradoxically, an
      increase in phase angle during hydration predicted poorer survival and
      preexisting intracellular dehydration, cachexia, or poor membrane function.
      CONCLUSIONS: Phase angle and weight during hydration predict survival in cancer.

PMID- 19182218
TI  - Respiratory support in oncology ward setting: a prospective descriptive study.
AB  - BACKGROUND: Mechanical ventilation in cancer patients is a critical issue The
      present prospective descriptive study was designed (1) to assess the patient
      population needing respirator support in ward setting at a premier state-run
      oncology institute in India, (2) to observe and analyze the course of their
      disease while on respirator, and (3) to coordinate better quality of life
      measures in cancer patients at the institute based on the present study's
      outcomes. METHODS: Beginning from March 2005 to March 2006, all cancer patients
      who were connected to respirator in the wards were enrolled in the current study.
      Our anesthesiology department at the cancer institute also has primary
      responsibility for airway management and mechanical ventilation in high
      dependency units of oncology wards. Preventilation variables in cancer patients
      were assessed to judge the futility of mechanical ventilation in ward setting.
      Subsequently, patients were observed for disease course while on respirator.
      Final outcome with its etio-pathogenesis was correlated with predicted futility
      of mechanical ventilation. RESULTS: Over a period of 1 year, 132 (46 men and 86
      women) cancer patients with median age 40 years (range 1-75 years) were connected
      to respirator in oncology wards. Based on the preventilation variables and
      indications for respirator support, right prediction of medical futility and
      hospital discharge was made in 77% of patients. Underestimation and
      overestimation of survival to hospital discharge was made in 10% cases and 13%
      cases, respectively. CONCLUSION: Based on preventilation variables, prediction of
      outcome in cancer patients needing respirator support can be made in 77% cases.
      This high probability of prediction can be used to educate patients, and their
      families and primary physicians, for well-informed and documented advance
      directives, formulated and regularly revised DNAR policies, and judicious use of
      respirator support for better quality-of-life outcomes.

PMID- 19182219
TI  - The Nrf2-antioxidant response element signaling pathway and its activation by
      oxidative stress.
AB  - A major mechanism in the cellular defense against oxidative or electrophilic
      stress is activation of the Nrf2-antioxidant response element signaling pathway,
      which controls the expression of genes whose protein products are involved in the
      detoxication and elimination of reactive oxidants and electrophilic agents
      through conjugative reactions and by enhancing cellular antioxidant capacity. At
      the molecular level, however, the regulatory mechanisms involved in mediating
      Nrf2 activation are not fully understood. It is well established that Nrf2
      activity is controlled, in part, by the cytosolic protein Keap1, but the nature
      of this pathway and the mechanisms by which Keap1 acts to repress Nrf2 activity
      remain to be fully characterized and are the topics of discussion in this
      minireview. In addition, a possible role of the Nrf2-antioxidant response element
      transcriptional pathway in neuroprotection will also be discussed.

PMID- 19182221
TI  - Linnaean sources and concepts of orchids.
AB  - BACKGROUND: Linnaeus developed a robust system for naming plants and a useful, if
      mechanical, system for classifying them. His binomial nomenclature proved the
      catalyst for the rapid development of our knowledge of orchids, with his work on
      the family dating back to 1737 in the first edition of his Genera Plantarum. His
      first work devoted to orchids, indeed the first monograph of the family, was
      published in 1740 and formed the basis for his account in Species Plantarum,
      published in 1753, in which he gave a binomial name to each species. Given the
      overwhelming number of orchids, he included surprisingly few - only 62 mostly
      European species - in Species Plantarum, his seminal work on the plants of the
      world. This reflects the European origin of modern botany and the concentration
      of extra-European exploration on other matters, such as conquest, gold and useful
      plants. Nevertheless, the scope of Linnaeus' work is broad, including plants from
      as far afield as India, Japan, China and the Philippines to the east, and eastern
      Canada, the West Indies and northern South America to the west. In his later
      publications he described and named a further 45 orchids, mostly from Europe,
      South Africa and the tropical Americas. SCOPE: The philosophical basis of
      Linnaeus' work on orchids is discussed and his contribution to our knowledge of
      the family assessed. His generic and species concepts are considered in the light
      of current systematic ideas, but his adoption of binomial nomenclature for all
      plants is his lasting legacy.

PMID- 19182220
TI  - Novel thigmomorphogenetic responses in Carica papaya: touch decreases anthocyanin
      levels and stimulates petiole cork outgrowths.
AB  - BACKGROUND AND AIMS: Because of its rapid growth rate, relative ease of
      transformation, sequenced genome and low gene number relative to Arabidopsis, the
      tropical fruit tree, Carica papaya, can serve as a complementary genetic model
      for complex traits. Here, new phenotypes and touch-regulated gene homologues have
      been identified that can be used to advance the understanding of
      thigmomorphogenesis, a multigenic response involving mechanoreception and
      morphological change. METHODS: Morphological alterations were quantified, and
      microscopy of tissue was conducted. Assays for hypocotyl anthocyanins, lignin and
      chlorophyll were performed, and predicted genes from C. papaya were compared with
      Arabidopsis touch-inducible (TCH) and Mechanosensitive channel of Small
      conductance-like genes (MscS-like or MSL). In addition, the expression of two
      papaya TCH1 homologues was characterized. KEY RESULTS: On the abaxial side of
      petioles, treated plants were found to have novel, hypertrophic outgrowths
      associated with periderm and suberin. Touched plants also had higher lignin,
      dramatically less hypocotyl anthocyanins and chlorophyll, increased hypocotyl
      diameter, and decreased leaf width, stem length and root fresh weight. Papaya was
      found to have fewer MSL genes than Arabidopsis, and four touch-regulated genes in
      Arabidopsis had no counterparts in papaya. Water-spray treatment was found to
      enhance the expression of two papaya TCH1 homologues whereas induction following
      touch was only slightly correlated. CONCLUSIONS: The novel petiole outgrowths
      caused by non-wounding, mechanical perturbation may be the result of hardening
      mechanisms, including added lignin, providing resistance against petiole
      movement. Inhibition of anthocyanin accumulation following touch, a new
      phenotypic association, may be caused by diversion of p-coumaroyl CoA away from
      chalcone synthase for lignin synthesis. The absence of MSL and touch-gene
      homologues indicates that papaya may have a smaller set of touch-regulated genes.
      The genes and novel touch-regulated phenotypes identified here will contribute to
      a more comprehensive view of thigmomorphogenesis in plants.

PMID- 19182222
TI  - Using synchrotron X-ray fluorescence microprobes in the study of metal
      homeostasis in plants.
AB  - BACKGROUND AND AIMS: This Botanical Briefing reviews the application of
      synchrotron X-ray fluorescence (SXRF) microprobes to the plant sciences; how the
      technique has expanded our knowledge of metal(loid) homeostasis, and how it can
      be used in the future. SCOPE: The use of SXRF microspectroscopy and
      microtomography in research on metal homeostasis in plants is reviewed. The
      potential use of SXRF as part of the ionomics toolbox, where it is able to
      provide fundamental information on the way that plants control metal homeostasis,
      is recommended. CONCLUSIONS: SXRF is one of the few techniques capable of
      providing spatially resolved in-vivo metal abundance data on a sub-micrometre
      scale, without the need for chemical fixation, coating, drying or even sectioning
      of samples. This gives researchers the ability to uncover mechanisms of plant
      metal homeostasis that can potentially be obscured by the artefacts of sample
      preparation. Further, new generation synchrotrons with smaller beam sizes and
      more sensitive detection systems will allow for the imaging of metal distribution
      within single living plant cells. Even greater advances in our understanding of
      metal homeostasis in plants can be gained by overcoming some of the practical
      boundaries that exist in the use of SXRF analysis.

PMID- 19182223
TI  - Phylogenetic relationships and molecular adaptation dynamics of human
      rhinoviruses.
AB  - Human rhinoviruses (HRVs) are responsible for nearly 50% of all common cold
      infections. Ordinarily, HRV infections are mild and self-limiting; nonetheless,
      every year they result in significant loss of economic productivity and
      substantial inappropriate antibiotic use. Development of effective vaccine and
      antiviral prophylaxis against HRV has been hampered by the extensive antigenic
      diversity present among the nearly 100 serotypes. To gain new insights into the
      evolutionary processes that create the genetic diversity present among HRVs, we
      tested for recombination and selection for individual genes and the coding genome
      for 45 HRV serotypes using estimated phylogenetic relationships. Although the
      structural capsid genes and nonstructural genes recovered incongruent tree
      topologies, no recombination was detected using substitution methods. Therefore,
      the coding genome was determined to be appropriate for phylogenetic tests.
      Results of the Shimodaira-Hasegawa (SH) test support the hypothesis that the
      capsid genes recover a different evolutionary history than the nonstructural
      genes. Our best phylogenetic estimate based on the coding genome suggests that
      HRV-B is more closely related to enterovirus than to HRV-A; however, several
      alternative phylogenetic hypotheses were not rejected by the SH test. Positive
      selection was examined by using two different approaches; d(N)/d(S) rate ratio
      and the physicochemical phenotypes for 31 amino acid properties. Analyses using
      d(N)/d(S) failed to detect positive selection. However, protein phenotypic
      expression appears to be a more sensitive approach. There was extensive
      stabilizing and destabilizing positive selection in HRV-A major and HRV-B
      serotypes for all proteins, except in 3A in HRV-B, which overlapped with
      functional, structural, and to a greater extent in uncharacterized genomic
      regions. In contrast, the evolution of HRV-A minor serotypes appears to be driven
      primarily by destabilizing selection. Our results demonstrate that HRV-A major,
      HRV-A minor, and HRV-B serotypes have not been similarly influenced by purifying
      selection.

PMID- 19182224
TI  - Patterns of diversity in HIV-related loci among subspecies of chimpanzee:
      concordance at CCR5 and differences at CXCR4 and CX3CR1.
AB  - Human immunodeficiency virus type 1 (HIV-1) arose in humans via zoonotic
      transmissions of simian immunodeficiency viruses (SIV(cpz)) from common
      chimpanzees, Pan troglodytes. Despite the close relatedness of the two viruses
      and their hosts, we do not yet understand what causes SIV(cpz) to be
      nonpathogenic in chimpanzees, and HIV/AIDS to be one of the most devastating
      infectious diseases to have emerged in humans. There have been a number of genes
      identified in humans that confer disease resistance/susceptibility toward HIV-1,
      but little is known about the evolution and diversity of most of these chemokine
      receptor genes in chimpanzees. Here we show that genetic variation in chimpanzees
      differs across the various loci related to HIV-1, and that the pattern of
      variation differs among the chimpanzee subspecies. For all three subspecies, low
      diversity at CCR5 is confined to a small area of chromosome 3, suggesting that a
      selective sweep at this locus may have predated subspeciation. In contrast,
      diversity and neutrality tests suggest differing evolutionary forces among
      subspecies at CXCR4 and CX(3)CR1, with directional selection (in Pan troglodytes
      vellerosus) and demographic expansion (Pan troglodytes troglodytes) offering the
      most likely scenarios. These are some of the first data demonstrating
      differentiation in functional loci among chimpanzee subspecies.

PMID- 19182225
TI  - The effect of suffering on generativity: accounts of elderly African American
      men.
AB  - BACKGROUND: This article focuses on attitudes to and behaviors of generativity in
      6 older African American (AA) men. METHODS: Data on generativity emerged from in
      depth qualitative research that explored experiences of suffering in community
      dwelling persons aged 80 years and over. RESULTS: For these AA men, experiences
      of racism were salient in stories of suffering, and suffering was intricately
      related to attitudes and behaviors of generativity. We placed men's narratives,
      showing the link between suffering and generativity, in 3 categories:
      Generativity is rooted in (a) suffering and in empathy for suffering others, (b)
      experiences of redemption from suffering, and (c) religious belief that assuages
      suffering. CONCLUSIONS: These AA men's generative behaviors were shaped by unique
      life experiences, including experiences of suffering. Bequeathing a legacy to
      succeeding generations was tied to suffering experiences, to the personal and
      communal identities that emerged from suffering, to the importance of inter- and
      intragenerational community, and to what men believed others needed from them.

PMID- 19182226
TI  - Homologs of genes associated with programmed cell death in animal cells are
      differentially expressed during senescence of Ipomoea nil petals.
AB  - In senescent petals of Ipomoea nil, we investigated the expression of genes
      showing homology to genes involved in animal programmed cell death (PCD). Three
      encoded proteins were homologous to apoptotic proteins in animals: Bax inhibitor
      1 (BI-1), a vacuolar processing enzyme (VPE; homologous to caspases) and a
      monodehydroascorbate reductase [MDAR; homologous to apoptosis-inducing factor
      (AIF)]. AIFs harbor an oxidoreductase domain and an apoptotic domain. MDARs
      exhibit homology to the AIF oxidoreductase domain, not to the apoptotic domain.
      The three other genes studied relate to autophagy. They encode homologs to
      vacuolar protein sorting 34 (VPS34) and to the Arabidopsis autophagy-related
      proteins 4b and 8a (ATG4b and ATG8a). The transcript abundance of MDAR decreased
      continuously, whereas that of the other genes studies exhibited a transient
      increase, except ATG4b whose abundance stayed high after an increase. Treatment
      with ethylene advanced the time to visible petal senescence, and hastened the
      changes in expression of each of the genes studied. In order to assess the role
      of VPS34 in petal senescence, we studied the effect of its inhibitor 3
      methyladenine (3-MA). 3-MA reduced the time to visible petal senescence, and also
      accelerated the time to DNA degradation. Remarkably, 3-MA increased the time to
      nuclear fragmentation, indicating that the time to visible petal senescence was
      independent of nuclear fragmentation. The data on 3-MA might suggest the idea
      that autophagy is not a cause of PCD, but part of the remobilization process.

PMID- 19182227
TI  - Hearing as a predictor of falls and postural balance in older female twins.
AB  - BACKGROUND: The purpose of the present study was to examine, first, whether
      hearing acuity predicts falls and whether the potential association is explained
      by postural balance and, second, to examine whether shared genetic or
      environmental effects underlie these associations. METHODS: Hearing was measured
      using a clinical audiometer as a part of the Finnish Twin Study on Aging in 103
      monozygotic and 114 dizygotic female twin pairs aged 63-76 years. Postural
      balance was indicated as a center of pressure (COP) movement in semi-tandem
      stance, and participants filled in a fall-calendar daily for an average of 345
      days after the baseline. RESULTS: Mean hearing acuity (better ear hearing
      threshold level at 0.5-4 kHz) was 21 dB (standard deviation [SD] 12). Means of
      the COP velocity moment for the best to the poorest hearing quartiles increased
      linearly from 40.7 mm(2)/s (SD 24.4) to 52.8 mm(2)/s (SD 32.0) (p value for the
      trend = .003). Altogether 199 participants reported 437 falls. Age-adjusted
      incidence rate ratios (IRRs) for falls, with the best hearing quartile as a
      reference, were 1.2 (95% confidence interval [CI] = 0.4-3.8) in the second, 4.1
      (95% CI = 1.1-15.6) in the third, and 3.4 (95% CI = 1.0-11.4) in the poorest
      hearing quartiles. Adjustment for COP velocity moment decreased IRRs markedly.
      Twin analyses showed that the association between hearing acuity and postural
      balance was not explained by genetic factors in common for these traits.
      CONCLUSION: People with poor hearing acuity have a higher risk for falls, which
      is partially explained by their poorer postural control. Auditory information
      about environment may be important for safe mobility.

PMID- 19182228
TI  - Elevated serum advanced glycation end products and poor grip strength in older
      community-dwelling women.
AB  - BACKGROUND: Advanced glycation end products (AGEs) have been implicated in the
      pathogenesis of diabetes, heart disease, and kidney failure and may potentially
      affect skeletal muscle. Whether AGEs are associated with poor muscle strength is
      unknown. METHODS: Serum carboxymethyl-lysine (CML), a dominant AGE, circulating
      soluble form of receptor for advanced glycation end products (sRAGE), and
      endogenous secretory receptor for advanced glycation end product (esRAGE) and
      grip strength were measured in 559 moderately to severely disabled women, age 65
      and older, in the Women's Health and Aging Study I in Baltimore, Md. RESULTS:
      Mean (standard deviation) grip strength among women in the highest quartile of
      serum CML compared with women in the lower three quartiles was 18.6 and 20.0 kg,
      respectively (p = .002), adjusting for age, race, body mass index, cognitive
      dysfunction, depression, and diabetes. Serum sRAGE and esRAGE were not
      significantly associated with grip strength. CONCLUSIONS: Women with high serum
      AGEs have greater muscle weakness. Further studies are needed to determine
      whether AGEs, a potentially modifiable risk factor, are associated with physical
      performance and disability in older adults.

PMID- 19182229
TI  - Multiple hormonal deficiencies in anabolic hormones are found in frail older
      women: the Women's Health and Aging studies.
AB  - BACKGROUND: Alterations in anabolic hormones are theorized to contribute to aging
      and frailty, with most studies focusing on the relationship between individual
      hormones and specific age-associated diseases. We hypothesized that associations
      with frailty would most likely manifest in the presence of deficits in multiple
      anabolic hormones. METHODS: The relationships of serum levels of total IGF-1,
      DHEAS, and free testosterone (T) with frailty status (nonfrail, prefrail, or
      frail) were analyzed in 494 women aged 70-79 years enrolled in the Women's Health
      and Aging Studies I or II. Using multivariate polytomous regression, we
      calculated the odds of frailty for deficiency in each hormone (defined as the
      bottom quartile of the hormone) individually, as well as for a count of the
      hormones. RESULTS: For each hormone, in adjusted analyses, those with the
      deficiency were more likely to be frail than those without the deficiency,
      although this did not achieve statistical significance (IGF-1: odds ratio [OR]
      1.82, confidence interval [CI] 0.81-4.08; DHEAS: OR 1.68, CI 0.77-3.69; free T:
      OR 2.03, CI 0.89-4.64). Compared with those with no hormonal deficiencies, those
      with one deficiency were not more likely to be frail (OR 1.15, CI 0.49-2.68),
      whereas those with two or three deficiencies had a very high likelihood of being
      frail (OR 2.79, CI 1.06-7.32), in adjusted models. CONCLUSIONS: The absolute
      burden of anabolic hormonal deficiencies is a stronger predictor of frailty
      status than the type of hormonal deficiency, and the relationship is nonlinear.
      These analyses suggest generalized endocrine dysfunction in the frailty syndrome.

PMID- 19182230
TI  - Executive decline and dysfunction precedes declines in memory: the Women's Health
      and Aging Study II.
AB  - BACKGROUND: Understanding preclinical transitions to impairment in cognitive
      abilities associated with risks for functional difficulty and dementia. This
      study characterized in the Women's Health and Aging Study (WHAS) II 9-year
      declines and transitions to impairment across domains of cognition. METHODS: The
      WHAS II is an observational study of initially high-functioning, community
      dwelling women aged 70-80 years at baseline. Random-effects models jointly
      compared rates of decline, and discrete-time Cox models estimated hierarchies of
      incident clinical impairment on measures of psychomotor speed and executive
      function (EF) using the Trail Making Test and in immediate and delayed verbal
      recall using the Hopkins Verbal Learning Test. Patterns of transition were
      related to incidence of global cognitive impairment on the Mini-Mental State Exam
      (MMSE). RESULTS: Mean decline and impairment occurred first in EF and preceded
      declines in memory by about 3 years. Thereafter, memory decline was equivalent to
      that for EF. Over 9 years, 49% developed domain-specific impairments. Risk of
      incident EF impairment occurred in 37% of the sample and was often the first
      impairment observed (23.7%), at triple the rate for psychomotor speed (p < .01).
      Risk of immediate and delayed recall impairments was nearly double that for
      psychomotor speed (p values <.01). Incident impairment in EF and delayed recall
      was associated with greater risk for MMSE impairment. CONCLUSIONS: Executive
      dysfunction developed first among nearly one quarter of older women and was
      associated with elevated risk for global cognitive impairment. Because EF
      declines preceded memory declines and are important to efficient storage and
      retrieval EF represents an important target for interventions to prevent declines
      in memory and MMSE both of which are associated with progression to dementia.

PMID- 19182231
TI  - Education differences in life expectancy with cognitive impairment.
AB  - BACKGROUND: Low education has an impact on life expectancy and level of
      cognition, but little is known on its effect on life expectancy with cognitive
      impairment. METHODS: The Medical Research Council Cognitive Function and Ageing
      Study (MRC CFAS) collected population-based longitudinal data on people aged 65
      years and older including measures of education and cognitive impairment, using
      the Mini-Mental State Examination (MMSE), for five geographically diverse areas
      around England and Wales interviewed between 1991 and 2003. Transitions between
      health states were calculated using Markov chain methods. Life expectancy in
      different states of cognitive function as measured by MMSE were further explored
      for different education groups. The effect of fixed and educationally based cut
      points for cognitive impairment are investigated. RESULTS: Life expectancy spent
      with cognitive impairment is fairly constant with increasing age at around 1.4
      years in men and 2.5 years in women, though this reflects a large increase in the
      proportion of life spent with cognitive impairment. The differences seen between
      education groups for the proportion of total life with cognitive impairment (men
      13% and women 22% of life lived for low education vs men 7% and women 12% in high
      education group) disappear when education-adjusted cut points are used (10% in
      men and 17% in women at age 65 for all education groups). CONCLUSIONS: The
      results show that there is a substantial amount of life expectancy with cognitive
      impairment in both men and women. The impairment burden is just as great for
      those with high education as the lowest educated group.

PMID- 19182233
TI  - National registry data on implantable cardioverter defibrillator treatment: what
      are they useful for?

PMID- 19182232
TI  - Use of the Short Physical Performance Battery Score to predict loss of ability to
      walk 400 meters: analysis from the InCHIANTI study.
AB  - BACKGROUND: Early detection of mobility limitations remains an important goal for
      preventing mobility disability. The purpose of this study was to examine the
      association between the Short Physical Performance Battery (SPPB) and the loss of
      ability to walk 400 m, an objectively assessed mobility outcome increasingly used
      in clinical trials. METHODS: The study sample consisted of 542 adults from the
      InCHIANTI study aged 65 and older, who completed the 400 m walk at baseline and
      had evaluations on the SPPB and 400 m walk at baseline and 3-year follow-up.
      Multiple logistic regression models were used to determine whether SPPB scores
      predict the loss of ability to walk 400 m at follow-up among persons able to walk
      400 m at baseline. RESULTS: The 3-year incidence of failing the 400 m walk was
      15.5%. After adjusting for age, sex, education, body mass index, Mini-Mental
      State Examination, number of medical conditions, and 400 m walk gait speed at
      baseline, SPPB score was significantly associated with loss of ability to walk
      400 m after 3 years. Participants with SPPB scores of 10 or lower at baseline had
      significantly higher odds of mobility disability at follow-up (odds ratio [OR] =
      3.38, 95% confidence interval [CI]: 1.32-8.65) compared with those who scored 12,
      with a graded response across the range of SPPB scores (OR = 26.93, 95% CI: 7.51
      96.50; OR = 7.67, 95% CI: 2.26-26.04; OR = 8.28, 95% CI: 3.32-20.67 for SPPB < or
      = 7, SPPB 8, and SPPB 9, respectively). CONCLUSIONS: The SPPB strongly predicts
      loss of ability to walk 400 m. Thus, using the SPPB to identify older persons at
      high risk of lower body functional limitations seems a valid means of recognizing
      individuals who would benefit most from preventive interventions.

PMID- 19182234
TI  - Serum potassium and arrhythmias.
AB  - Alterations in serum potassium levels are a common occurrence in clinical
      practice and entail a significant proarrhythmic risk. The present review is a
      short tutorial meant to assist clinicians in the pathophysiological
      interpretation of arrhythmias caused by dyskalaemia.

PMID- 19182235
TI  - Transvenous cardiac resynchronization therapy in complex congenital heart
      diseases: dextrocardia with transposition of the great arteries after Mustard
      operation.
AB  - Cardiac resynchronization therapy revealed first promising results in patients
      with a congenital heart disease and a systemic right ventricle. Contrast-enhanced
      magnetic resonance imaging showed accessibility of the coronary sinus in an 18
      year-old male patient with mirror dextrocardia, d-transposition of the great
      arteries and ventricular septal defect (VSD) after Mustard operation and VSD
      patch closure. In literatures, transvenous lead placement is discussed in this
      anatomical setting, with opposed position of the ventricular leads and reliable
      lead characteristics.

PMID- 19182236
TI  - In vitro activity of tigecycline against multiple strains of Borrelia
      burgdorferi.
AB  - OBJECTIVES: To compare the antimicrobial activity of tigecycline and doxycycline
      against multiple isolates of Borrelia burgdorferi. METHODS: In vitro
      antimicrobial assays were carried out using a microdilution assay. The time
      needed to inhibit, immobilize and kill the B31 strain of B. burgdorferi was
      determined. The MIC, MBC and concentration needed to immobilize the organism were
      determined for each antimicrobial for various strains of B. burgdorferi. RESULTS:
      Tigecycline inhibited the growth of and killed the organism more rapidly than
      doxycycline. Tigecycline was able to kill B. burgdorferi within 24 h at
      clinically achievable concentrations (<1 mg/L). In contrast, doxycycline was
      bacteriostatic and required 48-72 h to achieve its maximal inhibitory effect. The
      anti-Borrelia activity of the antibiotics was tested against 20 different
      isolates from three species. Tigecycline was 16- to 1000-fold more active than
      doxycycline at immobilizing Borrelia for the 20 isolates tested. CONCLUSIONS: We
      demonstrate that the in vitro activity of tigecycline against B. burgdorferi is
      superior to that of doxycycline. Tigecycline acted more rapidly and was
      bactericidal, whereas doxycycline was bacteriostatic and required a more
      prolonged co-incubation to achieve its maximal inhibitory effect.

PMID- 19182237
TI  - Diversity of carbapenem resistance mechanisms in Acinetobacter baumannii from a
      Taiwan hospital: spread of plasmid-borne OXA-72 carbapenemase.
AB  - OBJECTIVES: We investigated the molecular epidemiology of carbapenem-resistant
      Acinetobacter baumannii from a Taiwanese hospital and determined the mechanisms
      responsible for resistance. METHODS: Ninety-two consecutive meropenem-resistant
      A. baumannii isolates collected between January 2005 and June 2007 were screened
      for genes encoding OXA carbapenemases, metallo-beta-lactamases and for the carO
      gene encoding an outer membrane protein. PFGE was used to define clonal
      relatedness. PCR mapping was used to examine the linkage of insertion sequences
      and bla(OXA) genes. Southern hybridization of plasmid extracts and I-CeuI
      restricted chromosomal DNA was used to locate bla(OXA-24-like) genes. Sequences
      of selected bla(OXA-24-like) and carO genes were determined and loss of CarO
      expression was confirmed by SDS-PAGE. RESULTS: Most (70/92, 76%) isolates
      belonged to one of three PFGE pulsotypes, indicating clonal spread. Fifty-nine
      isolates, including the majority of those of pulsotypes I and III, produced OXA
      72 carbapenemase. The bla(OXA-72) gene was located on a 54 kb plasmid in selected
      isolates. Thirty-three (36%) isolates, including all 16 of pulsotype II, had
      ISAba1 preceding the bla(OXA-51-like) gene, promoting its expression. In addition
      to OXA-72 carbapenemase, two pulsotype I and three pulsotype III isolates did not
      produce CarO protein as the carO gene was disrupted by insertion of an ISAba1
      element. Two isolates of a minor pulsotype had a bla(OXA-58-like) gene and a
      single PFGE-unique isolate had a bla(OXA-23-like) gene. CONCLUSIONS: Although
      diverse mechanisms were identified, production of OXA-72 carbapenemase was the
      most common mechanism of carbapenem resistance in A. baumannii from this
      Taiwanese hospital. The plasmidic location of the gene had facilitated its spread
      to multiple strains.

PMID- 19182238
TI  - Effect of sildenafil on haemodynamic response to exercise and exercise capacity
      in Fontan patients.

PMID- 19182239
TI  - Renal allograft thrombosis.

PMID- 19182240
TI  - The impact of the assay for measuring albumin on corrected ('adjusted') calcium
      concentrations.
AB  - BACKGROUND: The K/DOQI guidelines recommend the use of albumin-corrected calcium
      (Ca), phosphate, parathyroid hormone (PTH) and calcium-phosphate product as
      therapeutic targets. The two most common assays for measuring albumin yield
      discordant results in uraemic patients, the Bromcresol purple (BCP) method
      providing lower albumin values than the Bromcresol green one (BCG). The aim of
      this study was to assess the impact of the assay on corrected Ca and, thus, on
      reaching recommended K/DOQI targets for corrected Ca and CaxP product. METHODS:
      We measured plasma albumin (both by BCG and BCP), total Ca and phosphate in all
      our chronic hemodialysis (HD) patients. Total Ca was corrected ("adjusted") for
      albumin level by a formula proposed by the K/DOQI. RESULTS: 89 patients were
      included, aged 71.2 +/- 11.5 years, on chronic hemodialysis for 29 (1-362)
      months. Albumin level was 3.78 +/- 0.24 g/dL by BCG and 3.12 +/- 0.27 by BCP ( p
      < 0.0001). Based on BCG albumin levels there were 12 cases of "hypocalcaemia"
      (<8.6 mg/dL), 3 cases of "hypercalcaemia" (>10 mg/dL) and 74 cases with "normal"
      Ca. The corresponding albumin levels were 3.9 +/- 0.2; 3.1 +/- 0.6 and 3.8 +/-
      0.2 g/dL, respectively. According to BCP albumin levels, only one patient was
      labelled as hypocalcaemia , 21 as hypercalcaemia et 67 as "normal" adjusted Ca
      (albumin 3.1; 3 +/- 0.3 and 3.2 +/- 0.3 g/dL, respectively). Depending on the use
      of BCG or BCP, a discrepancy was thus observed in 29 cases (32.6%): 18 cases were
      classified as hypercalcaemia when albumin was measured by BCP but were considered
      normal using BCG, whereas 11 cases classified as hypocalcaemia with BCG had
      normal adjusted Ca with BCP. Concerning CaxP product, 7 discrepancies were
      detected. DISCUSSION AND CONCLUSION: The choice of either BCG or BCP has a major
      impact on albumin-adjusted Ca and thus on reaching K/DOQI targets for Ca and CaxP
      product. Clinicians should take this fact into account for the interpretation of
      laboratory values and the prescription of drugs related to mineral metabolism and
      dialysate calcium concentration. The type of assay used for the measurement of
      albumin should also be recorded and its impact taken into account (or corrected)
      in multicentric studies and registries.

PMID- 19182241
TI  - The renal WNK kinase pathway: a new link to hypertension.

PMID- 19182242
TI  - Oligodendrogliomas: molecular biology and treatment.
AB  - Oligodendroglial tumors continue to receive much attention because of their
      relative sensitivity to chemotherapy. The histological diagnosis of
      oligodendroglial tumors is subject to considerable interobserver variation. The
      revised 2007 World Health Organization classification of brain tumors no longer
      accepts the diagnosis "mixed anaplastic oligoastrocytoma" if necrosis is present;
      these tumors should be considered glioblastomas (perhaps with oligodendroglial
      features). The 1p/19q codeletion that is associated with sensitivity to
      chemotherapy is mediated by an unbalanced translocation of 19p to 1q. Randomized
      studies have shown that patients with 1p/19q codeleted tumors also have a better
      outcome with radiotherapy. Histologically more atypical tumors are less likely to
      have this 1p/19q codeletion; here, other alterations usually associated with
      astrocytic tumors are often found. Some patients with tumors with classic
      histological features but no 1p/19q codeletion still have a very favorable
      prognosis. Currently, the best approach for newly diagnosed anaplastic
      oligodendroglial tumors is unclear. Early adjuvant chemotherapy does not provide
      a better outcome than chemotherapy at the time of progression. The value of
      combined chemoirradiation with temozolomide has not been proven in these tumors,
      and could at least theoretically be associated with greater neurotoxicity. Tumors
      with 1p and 19q loss can also be managed with early chemotherapy, while deferring
      radiotherapy to the time of further progression. The presently available second
      line chemotherapy results are modest, and better salvage treatments are
      necessary. The molecular explanation for the greater sensitivity of 1p/19q
      codeleted tumors is still unclear, and this could, in part, be explained by more
      frequent MGMT promoter gene methylation.

PMID- 19182243
TI  - Dual inhibition of the epidermal growth factor receptor pathway with cetuximab
      and erlotinib: a phase I study in patients with advanced solid malignancies.
AB  - PURPOSE: To determine the optimal dose of the antiepidermal growth factor
      receptor (EGFR) monoclonal antibody cetuximab that can be safely administered in
      combination with a standard daily dose of erlotinib in patients with advanced
      solid malignancies. PATIENTS AND METHODS: Patients with advanced solid
      malignancies who had failed standard chemotherapies received escalating doses of
      cetuximab without a loading dose (100, 200, 250 mg/m(2) i.v. weekly) in
      combination with a fixed dose of erlotinib (150 mg daily orally) until disease
      progression or unacceptable toxicity. RESULTS: Twenty-two patients were treated,
      including 14 patients (64%) with non-small cell lung cancer. Twenty patients
      received combination treatment at the highest dose level for a median of 5.5
      weeks (range, 1-31 weeks). One dose-limiting toxicity was observed: grade 3 skin
      rash. Overall, the most common adverse events (any grade, grade 3/4) were
      consistent with the safety profiles of the individual drugs: acneform rash (100%,
      9%), diarrhea (77%, 5%), and hypomagnesemia (59%, 12%). Seven of 18 evaluable
      patients (38.9%) had stable disease lasting for a median of 16.6 weeks (range,
      6.1-25.1 weeks). CONCLUSION: Dual EGFR inhibition with cetuximab and erlotinib is
      feasible; the observed toxicities were manageable and consistent with the safety
      profiles of the individual drugs. The recommended doses for phase II studies are
      250 mg/m(2) i.v. weekly for cetuximab and 150 mg daily orally for erlotinib.

PMID- 19182244
TI  - Epidemiologic studies are needed to clarify whether dental modalities could be
      predictors of bisphosphonate osteonecrosis of the jaw in breast cancer patients.

PMID- 19182246
TI  - In vivo imaging of the mouse model of X-linked juvenile retinoschisis with
      fourier domain optical coherence tomography.
AB  - PURPOSE: The purpose of this study was to investigate Fourier domain optical
      coherence tomography (FD OCT) as a noninvasive tool for retinal imaging in the
      Rs1h-knockout mouse (model for X-linked juvenile retinoschisis). METHODS: A
      prototype spectrometer-based FD OCT system was used in combination with a custom
      optical beam-scanning platform. Images of the retinas from wild-type and Rs1h
      knockout mice were acquired noninvasively with FD OCT with the specimen
      anesthetized. At the completion of the noninvasive FD OCT imaging, invasive
      retinal cross-sectional images (histology) were acquired from a nearby region for
      comparison to the FD OCT images. RESULTS: The retinal layers were identifiable in
      the FD OCT images, permitting delineation and thickness measurement of the outer
      nuclear layer (ONL). During FD OCT in vivo imaging of the Rs1h-knockout mouse,
      holes were observed in the inner nuclear layer (INL), and retinal cell
      disorganization was observed as a change in the backscattering intensity profile.
      Comparison of the ONL measurements acquired noninvasively with FD OCT to
      measurements taken using histology at nearby locations showed a degeneration of
      roughly 30% of the ONL by the age of 2 months in Rs1h-knockout mice relative to
      wild-type. CONCLUSIONS: FD OCT was demonstrated to be effective for noninvasive
      imaging of retinal degeneration and observation of retinal holes in Rs1h-knockout
      mice.

PMID- 19182247
TI  - In vivo quantitative evaluation of the rat retinal nerve fiber layer with optical
      coherence tomography.
AB  - PURPOSE: To determine whether optical coherence tomography (OCT) is useful for
      quantitative evaluation of the thickness of the rat retinal nerve fiber layer
      (RNFL) in an optic nerve crush model. METHODS: An OCT system was developed with a
      modified commercial time-domain OCT and a superluminescent diode with a bandwidth
      of 150 nm. Optical components were optimized to acquire rat retinal images. The
      right optic nerve was crushed intraorbitally with a clip. The left eye served as
      the untreated control. Circumpapillary OCT scans with a circle diameter of 500
      microm centered on the optic disc were performed before and 1, 2, and 4 weeks
      after the crush. Repeatability and reproducibility of RNFL thickness measurements
      were evaluated. The RNFL thicknesses at 400, 500, and 600 microm from the center
      of the optic disc determined by linear vertical OCT scans were compared with
      thicknesses in retinal sections. RESULTS: The mean RNFL thicknesses in
      circumpapillary OCT scans were 27.9 +/- 1.8, 29.2 +/- 2.4, 19.9 +/- 2.3, and 4.5
      +/- 3.6 microm before and 1, 2, and 4 weeks after the crush, respectively. RNFL
      thickness was unchanged 1 week after the crush, but then decreased significantly
      and progressively after the second week (P < 0.01). Coefficients of repeatability
      and reproducibility were less than 10% except for the crushed eyes at 4 weeks.
      RNFL thicknesses in OCT images correlated significantly with thicknesses
      determined histologically (r = 0.90, P < 0.001). CONCLUSIONS: OCT is a useful and
      valuable tool for quantitative evaluation of rat RNFL thickness.

PMID- 19182248
TI  - The effects of optic disc drusen on the latency of the pattern-reversal
      checkerboard and multifocal visual evoked potentials.
AB  - PURPOSE: To determine the effect of optic disc drusen on the latency of the
      pattern-reversal checkerboard visual evoked potentials (VEPs) and multifocal
      (mf)VEPs and to better understand the pathophysiology of the condition. METHODS:
      Eighteen eyes with optic disc drusen (10 patients) and 38 control eyes (19
      subjects) underwent VEP, mfVEP, and visual field testing. Only one eye of each
      individual, the one with the more affected visual field, was used in the
      analyses. The VEPs were recorded with a 15' and 60' reversing checkerboard
      pattern, and the mfVEPs were elicited by a 60-sector dartboard display. RESULTS:
      Unlike the VEP results, the mfVEP revealed a significant increase in the average
      monocular latency of the optic disc drusen group compared with that of the
      control group. The average mfVEP relative latency for the optic disc drusen group
      (4.1 ms) was greater than that (0.8 ms) in the control group. For monocular and
      interocular analyses, the average percentage of points delayed in the drusen
      group was significantly greater than that in the control group. CONCLUSIONS:
      Optic disc drusen produced significant latency delays on the mfVEP test but not
      on the VEP test, presumably due to the mfVEP's ability to detect the effects of
      local changes. The results are consistent with the hypothesis that local
      mechanical compression by optic disc drusen leads to abnormal retinal ganglion
      cell activity.

PMID- 19182249
TI  - Clinical application of autofluorescence densitometry with a scanning laser
      ophthalmoscope.
AB  - PURPOSE: Fundus autofluorescence (FAF) affects the overlying absorptive retinal
      pigments within the eye and can potentially be used to assess their density. This
      study reports a clinical application of FAF in measuring photopigments by
      scanning laser ophthalmoscopy (SLO). METHODS: The study group comprised 20
      healthy subjects, 4 patients with branch retinal artery occlusion (BRAO), 3 with
      macular hole, 3 with branch retinal vein occlusion (BRVO), and 4 with resolved
      central serous chorioretinopathy (CSC). Serial FAF images were taken during
      exposure to light. The intensity of the FAF was measured at the site of the
      macular hole or the photocoagulation laser burn in the eyes with BRVO. The
      autofluorescence optical density difference (fODD) was measured from the FAF
      images and mapped to elucidate the topographic pattern. RESULTS: The
      autofluorescence intensity showed little change at the sites of the macular holes
      or photocoagulation burns during exposure to light. The fODD was smallest at the
      center of the fovea and gradually increased with the eccentricity within 270 x
      270 pixels around the fovea in healthy subjects. The amplitude of the fODD did
      not change in the area affected with BRAO in comparison to the unaffected area.
      By contrast, the fODD decreased in the area of resolved serous retinal detachment
      in the eyes with CSC. CONCLUSIONS: In eyes with retinal disease, measuring the
      autofluorescence intensity using SLO is a feasible method of assessing the
      changes in the photopigments. Further studies comparing this approach with
      conventional methods for examining photopigments are needed.

PMID- 19182250
TI  - Effects of dorzolamide on choroidal blood flow, ciliary blood flow, and aqueous
      production in rabbits.
AB  - PURPOSE: To determine the effects of topical dorzolamide (a carbonic anhydrase
      inhibitor) on choroidal and ciliary blood flow and the relationship between
      ciliary blood flow and aqueous flow. METHODS: The experiments were performed in
      four groups of pentobarbital-anesthetized rabbits treated with topical
      dorzolamide (2%, 50 microL). In all groups, intraocular pressure (IOP) and mean
      arterial pressure (MAP) at the eye level were measured continuously by direct
      cannulation. In group 1, aqueous flow was measured by fluorophotometry before and
      after dorzolamide treatment. In group 2, aqueous flow was measured after
      dorzolamide at normal MAP and while MAP was held constant at 80, 55, or 40 mm Hg
      with occluders on the aorta and vena cava. In group 3, the same MAP levels were
      used, and ciliary blood flow was measured transsclerally by laser Doppler
      flowmetry (LDF). In group 4, choroidal blood flow was measured by LDF with the
      probe tip positioned in the vitreous over the posterior pole during ramp
      increases and decreases in MAP before and after dorzolamide. RESULTS: Dorzolamide
      lowered IOP by 19% (P < 0.01) and aqueous flow by 17% (P < 0.01), and increased
      ciliary blood flow by 18% (P < 0.01), which was associated with a significant
      reduction in ciliary vasculature resistance (-7%, P < 0.01). Dorzolamide shifted
      the relationship between ciliary blood flow and aqueous flow downward relative to
      the previously determined control relationship in the rabbit. Dorzolamide did not
      alter choroidal blood flow, choroidal vascular resistance, or the choroidal
      pressure flow relationship. CONCLUSIONS: Acute topical dorzolamide is a ciliary
      vasodilator and has a direct inhibitory effect on aqueous production, but it does
      not have a detectable effect on choroidal hemodynamics at the posterior pole in
      the rabbit.

PMID- 19182251
TI  - Cone-rod dependence in the rat retina: variation with the rate of rod damage.
AB  - PURPOSE: To assess the effect of accelerated rod damage on the integrity of cones
      in the rat retina. METHODS: Rhodopsin-mutant P23H-3 and Sprague-Dawley (SD) rats
      were raised in scotopic ambient conditions (12 hours dark, 12 hours 5 lux) and
      then exposed to photopic conditions (12 hours dark, 12 hours 300 lux). Rods and
      cones were assessed for cell death, outer segment (OS) morphology, and
      electroretinogram (ERG) responses. RESULTS: Cones in the P23H-retina were
      affected rapidly by photopic exposure. Exposure for 2 days caused 50% reductions
      in LM- and S-cone OS length and cone ERG responses, associated with and preceded
      by reductions in rod OS length and ERG responses. Although 2 days' exposure
      increased the rate of rod death, outer nuclear layer thinning was minimal, and no
      evidence of cone death was detected. In the SD retina, the same photopic exposure
      had no measurable effects on death rates, OS length, or ERG responses in either
      rods or cones. Longer (7 days) photopic exposure reduced cone and rod OS length
      and ERG responses in SD, as well as P23H-3 retinas, but less severely than in the
      P23H-3 strain. CONCLUSIONS: Cones are damaged rapidly in the P23H-3 retina when
      rod damage is accelerated by raised ambient illumination. This close dependence
      of cone integrity on rod integrity contrasts with the life-long persistence of
      cone function in the scotopic reared P23H-3 rat. In humans suffering comparable
      photoreceptor dystrophies, the maintenance of steady, low ambient light may, by
      minimizing acute rod damage, optimize the function of surviving cones.

PMID- 19182252
TI  - Multiplex ligation-dependent probe amplification of uveal melanoma: correlation
      with metastatic death.
AB  - PURPOSE: To evaluate multiplex ligation-dependent probe amplification (MLPA) of
      uveal melanoma as a predictive tool for metastatic death. METHODS: Uveal melanoma
      specimens of 73 patients treated between 1998 and 2000 were included. DNA samples
      were analyzed with MLPA evaluating 31 loci on chromosomes 1, 3, 6 and 8, and the
      results were correlated with metastatic death. RESULTS: The patients (27 women;
      46 men) had a median age of 60.6 years and a median follow-up of 6.2 years.
      Metastatic death occurred in 28 patients, correlating most strongly with
      chromosome 3 losses and gains on 8q (Cox univariate analysis, P < 0.001).
      Chromosome 6, region p25, gains correlated with good survival (Cox univariate
      analysis, P = 0.003). Prediction of metastatic death was improved by considering
      equivocal chromosome 3 losses as abnormal and by taking account of multiple risk
      factors, such as 8q gains, tumor diameter, and histologic features indicative of
      high-grade malignancy. CONCLUSIONS: MLPA analysis of uveal melanoma predicts
      metastatic death if statistically insignificant losses of chromosome 3 are
      considered together with gains in 8q as well as clinical stage and histologic
      grade of malignancy.

PMID- 19182253
TI  - Abnormal epithelial differentiation and tear film alteration in pinguecula.
AB  - PURPOSE: To investigate the differentiation of conjunctival epithelium and tear
      film function in pingueculae. METHODS: Twelve patients (12 eyes) who underwent
      simple excision for pingueculae were enrolled in the study. Immunostaining for
      K14, K19, K10, MUC5AC, Pax6, P63, Ki67, and K16 was performed on the pinguecula
      epithelium and normal conjunctival epithelium. Schirmer I test results and tear
      film break-up time (TFBUT) were evaluated just before and 1 month after surgery.
      RESULTS: Abnormal epidermal differentiation of pinguecula tissue, as evidenced by
      a decline in or absence of Pax6 expression, was accompanied by a decline in or
      absence of K19 keratin and MUC5AC, and an increase in K10 and K14 keratin.
      Furthermore, the pinguecula epithelium was actively proliferating, as evidenced
      by positive expression of Ki67, P63, and K16 keratin. The Schirmer I test results
      did not indicate any significant differences before and after surgery. However,
      the TFBUT was significantly prolonged 1 month after surgery compared with before
      surgery. CONCLUSIONS: Pinguecula is a condition of abnormal epithelial
      differentiation. It is characterized by squamous proliferation and metaplasia,
      resulting in instability of tear film with normal basic tear secretion.

PMID- 19182254
TI  - Postoperative use of bevacizumab as an antifibrotic agent in glaucoma filtration
      surgery in the rabbit.
AB  - PURPOSE: To evaluate the efficacy of bevacizumab as an antifibrotic agent after
      trabeculectomy in rabbits. METHODS: Forty-two rabbits underwent trabeculectomy
      and were randomly assigned to receive a postoperative course of seven
      subconjunctival injections of bevacizumab (1.25 mg, 25 mg/mL), 5-fluorouracil (5
      FU; 5 mg, 50 mg/mL), or balanced salt solution (BSS; 0.1 mL, control). Bleb
      survival and characteristics were evaluated over a 30-day period. The animals
      were killed on postoperative day (PD)10, PD20, and PD30. Histology and
      immunohistochemistry of the surgical eyes was performed to evaluate and grade the
      amount of scarring and fibrosis in each group. RESULTS: Bevacizumab significantly
      improved the outcome of filtration surgery in this model. Bevacizumab prolonged
      bleb survival compared with the 5-FU and control groups (16.0 +/- 1.3 days vs.
      6.9 +/- 0.6 and 7.4 +/- 0.85 days, respectively; P < 0.001). Bevacizumab-treated
      eyes had significantly larger and higher blebs than the control and 5-FU-treated
      groups (P < 0.05). Histologic analysis revealed that eyes treated with
      bevacizumab had significantly less postoperative scarring at the microscopic
      level at PD10 and PD20 (P = 0.009). CONCLUSIONS: Postoperative subconjunctival
      injection of bevacizumab is associated with improved trabeculectomy bleb survival
      in the rabbit model. Bevacizumab may be a useful agent for improving success and
      limiting scar tissue formation after trabeculectomy.

PMID- 19182255
TI  - Comprehensive mutational screening in a cohort of Danish families with hereditary
      congenital cataract.
AB  - PURPOSE: Identification of the causal mutations in 28 unrelated families and
      individuals with hereditary congenital cataract identified from a national Danish
      register of hereditary eye diseases. Seven families have been published
      previously, and the data of the remaining 21 families are presented together with
      an overview of the results in all families. METHODS: A combined screening
      approach of linkage analysis and sequencing of 17 cataract genes were applied to
      mutation analyses of total 28 families. RESULTS: The study revealed a disease
      locus in seven of eight families that were amenable to linkage analysis. All loci
      represented known genes, and subsequent sequencing identified the mutations.
      Mutations were found in eight genes, among them crystallins (36%), connexins
      (22%), and the transcription factors HSF4 and MAF (15%). One family carried a
      complex CRYBB2 allele of three DNA variants, and a gene conversion is the most
      likely mutational event causing this variant. Ten families had microcornea
      cataract, and a mutation was identified in eight of those. Most families
      displayed mixed phenotypes with nuclear, lamellar, and polar opacities and no
      apparent genotype-phenotype correlation emerged. CONCLUSIONS: In total, 28
      families were analyzed, and mutations were identified in 20 (71%) of them.
      Despite considerable locus heterogeneity, a high mutation identification rate was
      achieved by sequencing a limited number of major cataract genes. Provided these
      results are representative of Western European populations, the applied
      sequencing strategy seems to be suitable for the exploration of the large group
      of isolated cataracts with unknown etiology.

PMID- 19182256
TI  - Exploring functional candidate genes for genetic association in german patients
      with pseudoexfoliation syndrome and pseudoexfoliation glaucoma.
AB  - PURPOSE: Pseudoexfoliation (PEX) syndrome is a generalized elastic
      microfibrillopathy characterized by fibrillar deposits in intra- and extraocular
      tissues. Genetic and nongenetic factors are known to be involved in its
      etiopathogenesis. This study was focused on six functional candidate genes
      involved in PEX material deposition and the analysis of their potential
      association with PEX syndrome and PEX glaucoma (PEXG). METHODS: Fifty single
      nucleotide polymorphisms (SNPs) capturing >95% of overall genetic variance
      observed in Europeans at loci for FBN1, LTBP2, MFAP2, TGM2, TGF-b1, and CLU were
      genotyped in 333 unrelated PEX-affected and 342 healthy individuals of German
      origin, and a genetic association study was performed. To replicate the findings,
      two SNPs of the CLU gene were genotyped in a further 328 unrelated German
      patients with PEX as well as in 209 Italian patients with PEX and 190 Italian
      control subjects. RESULTS: Association with PEX was observed only for the SNP
      rs2279590 in intron 8 of the CLU gene coding for clusterin (corrected P = 0.0347,
      OR = 1.34) in our first German cohort. Likewise, a frequent haplotype
      encompassing the associated risk allele showed nominally significant association.
      None of remaining SNPs or SNP haplotypes were associated with PEX. The
      association found was confirmed in a second German cohort (P = 0.0244) but not in
      the Italian cohort (P = 0.7173). In addition, the association with CLU SNP
      rs2279590 was more significant in German patients with PEX syndrome than in those
      with PEXG. CONCLUSIONS: Genetic variants in the gene encoding clusterin may
      represent a risk factor for PEX in German patients but not in Italian patients.
      Variants in FBN1, LTBP2, MFAP2, TGF-b1, and TGM2 do not play a major role in the
      etiology of PEX syndrome, at least in German patients.

PMID- 19182257
TI  - T-cell suppression by programmed cell death 1 ligand 1 on retinal pigment
      epithelium during inflammatory conditions.
AB  - PURPOSE: To determine whether retinal pigment epithelial (RPE) cells can inhibit
      in vitro T-cell activation during inflammatory conditions. METHODS: Primary
      cultured RPE cells were established from normal C57BL/6 mice. Target bystander T
      cells were established from normal splenic T cells with anti-CD3 antibodies. T
      cell activation was assessed for proliferation by both examining [(3)H]-thymidine
      incorporation and the production of interferon (IFN)gamma or IL-17, as determined
      by ELISA. Expression of programed cell death 1 ligand 1 (PD-L1) on RPE or
      recombinant mouse IFNgamma-pretreated RPE cells was evaluated using
      oligonucleotide microarray, RT-PCR, immune staining, and flow cytometry.
      Expression of programed cell death 1 (PD-1)(+) on target T cells was evaluated by
      flow cytometry. Anti-mouse PD-L1 or PD-L2 neutralizing antibodies or target T
      cells from PD-1 knockout donors were used for the assay. RESULTS: IFNgamma
      pretreated RPE greatly suppressed activation of bystander T cells, especially the
      IFNgamma production by the target T cells (Th1 cells, but not Th17 cells) via
      direct cell contact. By examining cell surface candidate molecules, IFNgamma
      pretreated RPE expressed much higher levels of PD-L1 compared with the control
      nontreated RPE. Although primary RPE did not express the costimulatory molecule,
      expression of the molecule was induced on the surface of IFNgamma-pretreated RPE.
      PD-L1(+) RPE in the presence of IFNgamma selectively suppressed PD-1(+) T-cell
      activation. IFNgamma-pretreated RPE in the presence of anti-PD-L1 neutralizing
      antibodies, but not anti-PD-L2, failed to suppress T-cell production of IFNgamma.
      In addition, these RPE cells failed to suppress the production of IFNgamma by
      CD4(+) T cells from PD-1 null donors. CONCLUSIONS: Suppression of T-cell
      activation was obtained in cultures only when RPE expressed negative
      costimulators. Therefore, the authors propose that in vitro, Th1 cytokine-exposed
      ocular resident cells can express this molecule and it is this expression that
      causes the suppression of the bystander Th1-type cells.

PMID- 19182258
TI  - An evaluation of the reliability and validity of the visual functioning
      questionnaire (VF-11) using Rasch analysis in an Asian population.
AB  - PURPOSE: To determine whether the VF-11 is a valid scale to measure visual
      functioning in an Asian population with vision impairment. METHODS: Participants
      from the Singapore Malay Eye Study (SiMES) took part. Visual functioning was
      assessed by using the VF-11 (a modified version of VF-14 for an Asian
      population). Rasch analysis was performed on 618 participants with presenting
      visual acuity < 6/12 in the better eye. RESULTS: Disordered thresholds were
      initially evident, indicating that the categories were difficult to discriminate
      and required category collapsing (from 5 to 4) for nine items. The removal of two
      misfit items related to driving resulted in a fit of the VF-9 data to the Rasch
      model (chi(2) = 50.5, df = 27, P = 0.005). There were no more misfit items. The
      person separation reliability value was 0.82 which demonstrates that the VF-9 has
      sufficient ability to discriminate between at least two groups of participants
      with different levels of visual functioning. The VF-9 significantly
      differentiated patients stratified by visual acuity demonstrating adequate
      criterion validity. All items were free of differential item functioning, and
      there was no evidence of multidimensionality. Targeting of person ability and
      item difficulty was suboptimal, although this is inevitable in a population-based
      survey where most people would not be disabled. CONCLUSIONS: Although the Rasch
      modified VF-9 scale achieved fit to the Rasch model, its suboptimal targeting
      suggests that the instrument does not have the range of items to assess the
      impact of vision impairment across the severity spectrum of vision loss in this
      population.

PMID- 19182259
TI  - Variation of angle parameters in asians: an anterior segment optical coherence
      tomography study in a population of singapore malays.
AB  - PURPOSE: To assess variations in angle parameters using anterior segment optical
      coherence tomography (AS-OCT) and to investigate demographic, ocular and systemic
      associations of angle width. METHODS: This was a substudy of a population based,
      cross-sectional survey of 3280 (78.7% response rate) Malay people aged 40 to 80
      years in Singapore. All participants underwent a standardized interview and
      ocular and systemic examination. AS-OCT was performed on 291 consecutive patients
      in standardized dark conditions. Angle opening distance (AOD-500) and trabecular
      iris space area (TISA-500) 500 microm from the scleral spur were determined for
      the nasal and temporal angles. Anterior chamber depth (ACD) was also measured.
      RESULTS: AS-OCT measurements were analyzed in 239 (82.1%) right eyes. Mean AOD
      500 was smaller in women than in men, both nasally (0.255 vs. 0.293 mm, P =
      0.026) and temporally (0.245 vs. 0.286 mm, P = 0.023). Mean TISA-500 was smaller
      in women in the nasal quadrant only (0.104 vs. 0.117 mm, P = 0.035). Mean ACD was
      smaller in women than in men (2.71 vs. 2.87 mm, P = 0.001). Multiple linear
      regression showed that axial length and ACD were significantly associated with
      AOD-500 and TISA-500 both nasally (adjusted R(2) = 0.34 for AOD-500 and 0.20 for
      TISA-500) and temporally (adjusted R(2) = 0.35 for AOD-500 and 0.24 for TISA
      500). Body mass index, HbA(1c), systolic blood pressure, intraocular pressure,
      cup-to-disc ratio, and central corneal thickness were not significantly
      associated with AOD-500, TISA-500, or ACD. CONCLUSIONS: In this Malay population,
      angle width measured by AS-OCT was smaller in women than in men, and in eyes with
      shorter axial length and shallower ACD.

PMID- 19182260
TI  - Effects of dioxin on vascular endothelial growth factor (VEGF) production in the
      retina associated with choroidal neovascularization.
AB  - PURPOSE: Cigarette smoking is the most consistent risk factor for age-related
      macular degeneration (AMD), especially the choroidal neovascularization (CNV)
      mediated exudative type. Dioxins and dioxin-like compounds have various effects
      on living organisms and are also contained in cigarette smoke. However, the
      effects of dioxins on the eye remain elusive. In this study, the authors examined
      the association between dioxins and neovascularization in the eye. METHODS:
      C57BL/6 mice were injected intraperitoneally with 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) every other day for 14 days. Messenger RNA expression of cytochrome
      P450 (CYP)1A1, CYP1B1, vascular endothelial growth factor (VEGF)-A and VEGF-B,
      and VEGF production were examined in the eyes of TCDD-treated mice and in human
      retinal pigment epithelial cell lines (ARPE-19) exposed to TCDD. In addition, CNV
      was induced by photocoagulation in mice injected with TCDD, and the volume of CNV
      was compared by fluorescence-labeled choroidal flat mount. RESULTS: TCDD injected
      intraperitoneally increased CYP1A1 mRNA expression in the iris/ciliary body and
      retina, indicating that TCDD acts directly on ocular tissues through the aryl
      hydrocarbon receptor (AhR) to promote the transcription of target genes. TCDD
      also promoted VEGF-A mRNA expression in the retina and the retinal pigment
      epithelium. TCDD-induced VEGF production at the molecular level was also observed
      in vivo by immunohistochemistry and in vitro using ARPE-19. Moreover, the
      injection of TCDD significantly exacerbated photocoagulation-induced CNV in mice.
      CONCLUSIONS: The authors demonstrate that dioxins are among the factors inducing
      abnormal vascularization in the eye through VEGF production mediated by AhR
      signaling.

PMID- 19182261
TI  - Suppression of choroidal neovascularization in lectin-like oxidized low-density
      lipoprotein receptor type 1-deficient mice.
AB  - PURPOSE: To elucidate the role of the scavenger receptor, lectin-like oxidized
      low-density lipoprotein receptor type 1 (LOX-1), in the formation of choroidal
      neovascularization (CNV). METHODS: CNV was induced by laser photocoagulation of
      the ocular fundus in mice. The expression of LOX-1 mRNA and protein after laser
      injury was determined by real-time RT-PCR and Western blot analysis. Gelatin
      zymography was used to measure the activity of matrix metalloproteinase (MMP)-2
      and pro-MMP-9, and ELISA was used to determine monocyte chemoattractant protein
      (MCP)-1 and vascular endothelial growth factor (VEGF) levels. At 14 days after
      laser injury, the extent of CNV was evaluated by fluorescein angiography and
      lectin staining using confocal microscopy. RESULTS: In wild-type mice, the
      relative expression level of LOX-1 mRNA compared with the control increased
      significantly 6 hours after laser injury and peaked 12 hours after laser injury
      (P = 0.011 and P = 0.0006, respectively), and the expression of LOX-1 protein was
      also detected 1 and 3 days after laser injury. Increases in MMP-2, pro-MMP2, and
      pro-MMP-9 after laser injury were reduced in LOX-1-deficient mice compared with
      wild-type mice. At 3 days after laser injury, increases in MCP-1 and VEGF
      significantly decreased in LOX-1-deficient mice compared with wild-type mice (P =
      0.014 and P = 0.001, respectively). Morphometric analyses revealed that the
      induction of CNV formation was significantly inhibited in LOX-1-deficient mice.
      CONCLUSIONS: These results suggest that LOX-1 plays an important role in the
      formation of CNV. This scavenging system might thus be a novel therapeutic target
      for CNV.

PMID- 19182263
TI  - Media literacy as a violence-prevention strategy: a pilot evaluation.
AB  - Youth violence is a major unresolved public health problem in the United States
      and media exposure to violence is a synergistic source of this national problem.
      One media literacy curriculum designed specifically to address this issue is
      Beyond Blame: Challenging Violence in the Media. The purpose of this pilot study
      was to examine the curriculum's feasibility as a full-scale intervention.
      Intervention and control groups were similar with respect to knowledge of the
      Beyond Blame curriculum at baseline. Intervention students scored much higher on
      the posttest compared with the control students. The majority (90.2%) of the
      intervention students reported a significant increase in pre- to posttest score
      compared with only 18.8% of the control students (p < .0001). The magnitude of
      the score increase for intervention students was much greater than those in the
      control group. Several intervention students (N = 49; 19.9%) improved their score
      by 12 or more points compared with the control students who showed only a 1- to 7
      point score increase (N = 3; 18.8%; p < .0001). The pre-and posttest scores were
      similar for males and females. Three of the six intervention classrooms scored
      higher on both the pretest and posttest compared with the other three classrooms.

PMID- 19182264
TI  - Assessment and outcomes of HealthPartners 10,000 Steps program in an academic
      work site.
AB  - The authors examined the feasibility, acceptability, and potential for physical
      activity behavior change of a 21-week, 10,000 Steps program in an academic work
      site. In a pre-post, noncontrolled study design, participants were supplied a
      pedometer, online resource, and health promotional activities. Means, medians,
      ranges, and frequencies of self-reported average daily steps (ADS) described
      physical activity behavior change. An online exit survey assessed the
      acceptability of the intervention. Of 1,322 eligible participants, 619 (47%)
      registered; 74% of participants tracked step counts at least once, and 57 (9%)
      tracked them all 21 weeks. The proportion of cohort participants with < 7,499 ADS
      tracking all 21 weeks was significantly less than that same cohort tracking only
      at baseline (p < .02). Survey results showed that 85% of the participants
      reported general satisfaction with content and navigation of the program Web
      site. Results suggest elements of feasibility and acceptability but limited
      potential for physical activity behavior change. Future studies should assess pre
      enrollment ADS and barriers to retaining participants.

PMID- 19182262
TI  - Iron chelation protects the retinal pigment epithelial cell line ARPE-19 against
      cell death triggered by diverse stimuli.
AB  - PURPOSE: Cell death can be induced by exogenous reactive oxygen species (ROS).
      Endogenous ROS can also play a role in cell death triggered by agents that are
      not themselves ROS. One of the most potent ROS-generating systems is the iron
      catalyzed Fenton reaction. Herein, the authors tested whether iron plays an
      important role in cell death induced by diverse stimuli in retinal pigment
      epithelial (RPE) cells. METHODS: The ability of the iron chelator salicylaldehyde
      isonicotinoyl hydrazone (SIH) to chelate intracellular labile iron was tested in
      the human cell line ARPE-19. The ability of SIH to protect against RPE cell death
      induced by hydrogen peroxide, staurosporine, anti-Fas, and exposure to A2E plus
      blue light was determined. ROS production by staurosporine was assessed in the
      presence and absence of SIH. The protective activity of SIH was compared with
      that of other iron chelators and an antioxidant. RESULTS: Acute exposure to SIH
      was nontoxic and at least partially protective against cell death induced by all
      tested agents. On a molar basis, SIH was more protective against hydrogen
      peroxide than other iron chelators and an antioxidant. SIH decreased levels of
      staurosporine-induced ROS. CONCLUSIONS: Iron chelation with SIH can decrease
      levels of ROS and protect RPE cells against cell death induced by diverse
      stimuli. These results suggest a central role for iron in cell death pathways,
      potentially involving the generation of oxidative stress. SIH or related iron
      chelators may prove useful for protection against diseases involving RPE death,
      such as AMD.

PMID- 19182265
TI  - Reflection on my mother dying: a story of caring shame.
AB  - In this story, the author reflects on visiting his mother the day before she
      died, just a few days after her transfer from the general hospital. Previously,
      his mother had lived in a residential home for 3 years before stumbling and
      breaking her leg. Then she required hospital admission. Three months later,
      clearly dying, "they" transferred her to the nursing home. The story is an expose
      of poor care and the despair this caused for the family at such a critical time.
      The story is offered as a call for action.

PMID- 19182266
TI  - Self-renewal in nursing leadership: the lived experience of caring for self.
AB  - Nurse leaders are often vulnerable to stress as experienced in the
      workenvironment, including long hours, patient overloads, and challenging work
      settings. If ignored, these stressors may lead to physical, emotional and
      behavioral symptoms with possible resulting medical errors, absenteeism, health
      challenges, and job burnout. PURPOSE: This study was designed to assess the
      meaning of caring for self by registered nurse leaders who had participated in a
      holistic caring-for-self project. DESIGN/SETTING: Hermeneutic phenomenology was
      the research method used in this study to explore the lived experience of caring
      for self from the perspective of 10 nursing leaders. Individual taped interviews
      were conducted with the participants in a private room in their work setting, a
      185-bed community hospital. FINDINGS: The nursing leaders communicated four
      common themes: Reflections on the Journey of Life, Why to Care for Self on the
      Journey, How to Care for Self on the Journey, and the Wisdom Learned Along the
      Path. CONCLUSIONS: Based on the reflections of the nursing leaders,
      recommendations include implementing creative, holistic methods to encourage self
      renewal in the work environment.

PMID- 19182267
TI  - Embodying nursing openheartedness: an existential perspective.
AB  - In this article, the authors attempt to articulate one view of the nature of
      nursing openheartedness and its central role for guiding caring in complex
      nursing situations. To do this, vignettes of everyday nursing life situations are
      used to illustrate the following three essential dimensions that constitute
      nursing openheartedness: (a) the infinity of otherness: keeping open the other's
      difference, (b) embodiment: our shared vulnerable heritage, and (c) practical
      responsiveness: embracing the value of the objectified gaze and technology. Each
      of these dimensions is philosophically informed by distinctive insights from the
      work of Heidegger, Levinas, and Merleau Ponty. Furthermore, guided by Gendlin's
      contributions regarding the nature of embodied understanding, a writing style
      that attempts to present the nature of nursing openheartedness as a possible
      experience rather than as an abstract theory is employed.

PMID- 19182268
TI  - Health promotion through forgiveness intervention.
AB  - The purpose of this article is to offer evidence-based forgiveness interventions
      clinically useful to nurses in holistic health promotion for individuals,
      families, and communities. Forgiveness interventions are developed and described
      within four approaches inspired by midrange nursing theorists who have adapted
      their theories from Bandura's Social Learning Theory and Frankl's Theory of
      Meaning. Interventions are also assimilated from a comprehensive review of
      theoretical and research literature. The four interventional approaches include
      persuasive information, vicarious experience, awareness of physiological
      reactions, and enactive attainment. Barriers to implementation are discussed as
      well as ways to individualize the interventions.

PMID- 19182269
TI  - DNA-binding Domain within the Brh2 N Terminus Is the Primary Interaction Site for
      Association with DNA.
AB  - The C-terminal region of Brh2 (Brh2(CT)), the BRCA2 homolog in Ustilago maydis,
      is highly conserved and aligns with the DSS1/DNA-binding domain (DBD) of
      mammalian BRCA2, while the N-terminal region (Brh2(NT)) is poorly conserved and
      has no obvious functional domain except for the single Rad51-interacting BRC
      element. Paradoxically, Brh2(NT), but not Brh2(CT), complements the DNA repair
      and recombination deficiency of the brh2 mutant. We show here that Brh2(NT)
      exhibits an unexpected DNA binding activity with properties similar to that of
      the full-length protein. Deletion mapping localized the region responsible for
      the DNA binding activity to a stretch of residues between the BRC element and the
      canonical DBD. A heterologous DNA-binding domain from the large subunit of
      replication protein A substituted for the endogenous binding region within
      Brh2(NT) in supporting DNA repair. Rad51-promoted strand invasion was stimulated
      by Brh2(NT), but required the presence of the BRC element. The findings suggest a
      model in which Brh2(NT) serves as the principal site for association with DNA,
      while the Brh2(CT) provides a means for regulation.

PMID- 19182271
TI  - Enteric serotonergic neurones ... finally!

PMID- 19182270
TI  - Phycourobilin in trichromatic phycocyanin from oceanic cyanobacteria is formed
      post-translationally by a phycoerythrobilin lyase-isomerase.
AB  - Most cyanobacteria harvest light with large antenna complexes called
      phycobilisomes. The diversity of their constituting phycobiliproteins contributes
      to optimize the photosynthetic capacity of these microorganisms. Phycobiliprotein
      biosynthesis, which involves several post-translational modifications including
      covalent attachment of the linear tetrapyrrole chromophores (phycobilins) to
      apoproteins, begins to be well understood. However, the biosynthetic pathway to
      the blue-green-absorbing phycourobilin (lambda(max) approximately 495 nm)
      remained unknown, although it is the major phycobilin of cyanobacteria living in
      oceanic areas where blue light penetrates deeply into the water column. We
      describe a unique trichromatic phycocyanin, R-PC V, extracted from phycobilisomes
      of Synechococcus sp. strain WH8102. It is evolutionarily remarkable as the only
      chromoprotein known so far that absorbs the whole wavelength range between 450
      and 650 nm. R-PC V carries a phycourobilin chromophore on its alpha-subunit, and
      this can be considered an extreme case of adaptation to blue-green light. We also
      discovered the enzyme, RpcG, responsible for its biosynthesis. This monomeric
      enzyme catalyzes binding of the green-absorbing phycoerythrobilin at cysteine 84
      with concomitant isomerization to phycourobilin. This reaction is analogous to
      formation of the orange-absorbing phycoviolobilin from the red-absorbing
      phycocyanobilin that is catalyzed by the lyase-isomerase PecE/F in some
      freshwater cyanobacteria. The fusion protein, RpcG, and the heterodimeric PecE/F
      are mutually interchangeable in a heterologous expression system in Escherichia
      coli. The novel R-PC V likely optimizes rod-core energy transfer in
      phycobilisomes and thereby adaptation of a major phytoplankton group to the blue
      green light prevailing in oceanic waters.

PMID- 19182274
TI  - Incompetence among critical care nurses: a survey report.

PMID- 19182277
TI  - A new way to orient graduate nurses.

PMID- 19182278
TI  - Transcatheter and transapical aortic valve replacement.
AB  - Minimally invasive valve replacement is limited to bioprosthetic aortic and
      pulmonary valves for use in very specific populations of patients. Replacement
      via trans-catheter and transapical techniques should be used only in patients in
      whom traditional surgical replacement is deemed an unacceptable risk. Nursing
      management will focus heavily on care for comorbid conditions because of the high
      risk nature of the patients in whom these valves will initially be implanted.

PMID- 19182279
TI  - Femoral artery closure after cardiac catheterization.
AB  - After diagnostic and interventional cardiac catheterization, femoral artery
      closure devices offer quicker time to hemostasis, ambulation, and discharge than
      does manual compression. Nurses should understand how femoral artery closure
      devices work, the potential vascular complications that may occur with their use,
      and the recommended time to ambulation and discharge.

PMID- 19182280
TI  - The"broken heart syndrome": understanding Takotsubo cardiomyopathy.
AB  - "Broken heart syndrome," or takotsubo cardiomyopathy, is a spontaneously
      reversible form of cardio-myopathy that is often induced by emotional or physical
      stress. Signs and symptoms include chest pain, dyspnea, electrocardiographic
      changes, and elevated levels of cardiac biomarkers. Patients often have signs and
      symptoms of fluid overload and can have acute pulmonary edema. Most patients are
      postmenopausal women, many with no risk factors for coronary artery disease. The
      left ventricular abnormality reverses spontaneously in days or weeks.

PMID- 19182281
TI  - Further validation of the nonverbal pain scale in intensive care patients.
AB  - Pain assessment is difficult but vital for sedated patients receiving mechanical
      ventilation in ICUs. Few nonverbal scales have been developed for assessing pain,
      and few studies of their validity and reliability have been published. The
      authors compare the original and revised versions of the Nonverbal Pain Scale in
      sedated patients receiving mechanical ventilation in an ICU and present the
      results.

PMID- 19182282
TI  - Electrocardiography pitfalls and artifacts: the 10 commandments.
AB  - Artifacts are common in patients who require ECG monitoring. Artifacts can
      simulate arrhythmias such as atrial flutter and ventricular tachycardia and lead
      to inappropriate treatment. Electrode and lead misplacements are another common
      pitfall and can lead to ECG changes that may be interpreted as ischemic in origin
      and can mimic serious arrhythmias. A simplified algorithm (REVERSE is the
      mnemonic) may help clinicians correctly identify both suspected electrode
      misplacements and artifacts.

PMID- 19182283
TI  - Nurse-physician relationships in hospitals: 20,000 nurses tell their story.
AB  - "Good" relationships between nurses and physicians are important to high-quality
      patient care. Five different types of nurse-physician relationships exist on
      clinical units. What are the differences in the nurse-physician climate between
      magnet and comparison hospitals? What are the organizational structures and best
      leadership practices that help nurses develop collegial and collaborative
      relationships with physicians?

PMID- 19182284
TI  - Delirium in the intensive care unit: medications as risk factors.

PMID- 19182286
TI  - Implementation of cycled lighting in a single-room neonatal ICU.

PMID- 19182287
TI  - Pretreatment with nitroprusside for microcirculatory protection in saphenous vein
      graft interventions.
AB  - OBJECTIVES: We hypothesized that the prophylactic administration of sodium
      nitroprusside (NTP) during saphenous vein graft (SVG) PCI would ameliorate the
      detrimental effects of distal embolization and reduce the frequency and magnitude
      of post-procedural myonecrosis. METHODS: Sixty-four consecutive patients with
      normal preprocedural cardiac enzymes underwent SVG PCI without embolic protection
      devices and received prophylactic intragraft NTP before initial device
      activation. For each case, 2 control patients were selected in reverse
      chronologic order and were matched for stent use, thromboatherectomy device use,
      clinical presentation, presence of thrombus and pre-PCI thrombolysis in
      myocardial infarction (TIMI) flow. RESULTS: Mean patient age was 66 +/- 10 years,
      78% of whom were males. Stent and thromboatherectomy use was 95.3% and 3.1%,
      respectively in both groups (p = ns). Prior to intervention, TIMI < 3 flow was
      present in 26.6% of cases and in 24.2% of control patients (p = ns). Thrombus was
      present in 20.3% of cases and in 19.5% of controls (p = ns). Post-PCI creatinine
      kinase (CK)-MB elevation > 3 x the upper limit of normal (ULN) occurred in 6.3%
      of cases vs. 16.4% of controls (p = 0.049) and > 5 x ULN in 1.6% of cases
      vs.10.9% of controls (p = 0.022). In a multivariate regression model that
      included stent use, in-stent restenosis, thrombus presence, preprocedural TIMI 3
      flow, MI as procedural indication, NTP and glycoprotein IIb/IIIa use, NTP was the
      only independent and significant predictor of reduced post-procedural CK-MB
      elevation > 5 x ULN. CONCLUSION: Prophylactic administration of intragraft NTP
      during SVG PCIs results in a lower frequency and magnitude of post-procedural
      cardiac enzyme elevation.

PMID- 19182288
TI  - In-hospital percutaneous coronary intervention improves in-hospital survival in
      patients with acute inferior myocardial infarction particularly with right
      ventricular involvement.
AB  - OBJECTIVE: Assess the interaction between fibrinolysis and in-hospital
      percutaneous coronary intervention (PCI) in patients with inferior myocardial
      infarction (MI), particularly those with electrocardiographic evidence of right
      ventricular infarction (RVI). DESIGN: Retrospective observational study.
      PATIENTS: Consecutive patients with inferior MI identified from an MI registry
      between January 1998 and January 2004. INTERVENTIONS: Propensity analyses and
      multiple regression analysis were used to determine the mortality benefit of PCI.
      MAIN OUTCOME MEASURES: In-hospital morbidity and mortality. RESULTS: In total,
      465 patients with inferior MI received fibrinolytic therapy (median pain-to
      needle time of 167 minutes; IQR 100-311 minutes). The main predictors of PCI were
      recurrent chest pain, peak creatine kinase, age, reinfarction, presence of heart
      failure and male gender. Significant independent predictors of in-hospital
      mortality were age > or = 75 years, RVI, initial systolic blood pressure < or =
      80 mmHg, female gender and no in-hospital PCI. In-hospital PCI was performed in
      184/465 (40%) patients; 55 (30%) had rescue PCI performed < or = 6 hours post
      fibrinolysis, 45 (24%) within 6-24 hours and 84 (46%) > or = 24 hours. In
      hospital PCI was associated with reduced in-hospital mortality (PCI: 9 [5%] vs.
      no PCI: 40 [14%]; p < 0.001) mainly in those with RVI (PCI: 8 [8%] vs. no PCI 33
      [23%]; p = 0.002) compared with no RVI (PCI: 1 [1%] vs. no PCI 7 [5%]; p = 0.1).
      CONCLUSION: A strategy of timely fibrinolysis combined with in-hospital PCI
      including rescue PCI may result in a significant reduction in in-hospital
      mortality and morbidity in patients with inferior MI, particularly those with
      RVI.

PMID- 19182289
TI  - Clinical outcomes after percutaneous coronary intervention involving very long
      segments of drug-eluting stent implantation: single-center experience.
AB  - BACKGROUND: Data on effectiveness and safety following the implantation of very
      long segments of drug-eluting stents (DES) are lacking. AIM: To describe our
      experience of consecutive patients undergoing implantation of very long segments
      of DES (> 50 mm) in de novo coronary lesions. METHODS: We evaluated major in
      hospital complications, target lesion revascularization (TLR) rates and long-term
      outcomes in 88 consecutive patients (91 procedures) who underwent a single-vessel
      intervention with implantation of > 50 mm of overlapping DES to de novo lesions
      between October 2002 and October 2007. An additional 14 patients with long
      segments of in-stent restenosis, 10 receiving both DES and bare-metal stents for
      long-segment disease and 1 with long-segment disease in a saphenous vein graft
      were excluded from the study. Baseline clinical data, procedural outcomes and
      completed follow up were collected prospectively. RESULTS: Follow up was 100%
      complete up to April 30, 2008. The mean follow up was 26.5 months (6-60 months).
      The mean stent length was 70.6 mm (51-135 mm) and the average number of stents
      per vessel was 2.7 (2-5 stents). Acute complications included 1 case of acute
      stent thrombosis which was treated successfully, 1 case of aortic root
      dissection, and 1 case of retroperitoneal hemorrhage. The rate of non-Q-wave
      myocardial infarction (CKMB > 3 times normal) was 8%. During follow up, the rate
      of TLR was 6.5%. Five patients died, 4 of them due to noncardiac conditions. One
      death was attributed to possible late stent thrombosis (18 months) occurring
      suddenly 2 days post keloid repair. Two patients had definite very late stent
      thrombosis at 14 and 17 months. CONCLUSION: In our experience, the use of very
      long segments of DES is effective in treating diffuse de novo coronary artery
      lesions. However, longer-term follow up is necessary and more data are required
      to determine the optimum duration of dual antiplatelet therapy.

PMID- 19182290
TI  - Unique challenges of full metal jackets in the era of drug-eluting stents.

PMID- 19182291
TI  - Initial clinical experience using an ostial stent positioning system (Ostial Pro)
      for the accurate placement of stents in the treatment of coronary aorto-ostial
      lesions.
AB  - OBJECTIVE: To evaluate the safety and efficacy of a new nitinol stent positioning
      system to assist in the placement of aorto-ostial coronary stents. BACKGROUND:
      The stenting of aorto-ostial lesions is technically challenging. METHODS: We
      report the first clinical series using the Ostial Pro to assist in the precise
      placement of stents in coronary aorto-ostial lesions. These results were compared
      to matched cases performed without the ostial positioning system. RESULTS: The
      Ostial Pro is a simple nitinol device with self-expanding legs that are advanced
      just distal to the tip of the guiding catheter. The nitinol legs prevent the
      entry of the guiding catheter into the target vessel and align the tip of the
      guiding catheter. Using the Ostial Pro positioning device, angiographic and
      clinical success was achieved in 30/30 (100%) cases. Excellent stent positioning
      was confirmed by angiography (n = 30) and intravascular ultrasound (n = 28). The
      final true ostial dimension was larger than the stented segment minimum luminal
      diameter in 30/30 cases. In a matched consecutive cohort of 30 consecutive
      coronary aorto-ostial stent cases placed without the Ostial Pro, we observed an
      ostial stent malpositioning in 18/30 (60%) of cases (p < 0.0001 vs. cases
      performed with Ostial Pro). CONCLUSIONS: 1) The Ostial Pro is a new FDA-cleared
      nitinol device that is simple to use and effective in allowing the precise
      placement of stent(s) at the aorto-ostial location; 2) this approach appears to
      provide an efficient means to assure accurate stent placement and minimal
      residual stenosis in these difficult-to-treat lesions.

PMID- 19182292
TI  - Novel applications of noncardiac vascular devices for the treatment of coronary
      artery pathology.
AB  - Transcatheter percutaneous therapy for the treatment of vascular disease has
      markedly expanded over the last 20 years. This growth of endovascular technology
      has encouraged application of these modalities to vascular pathology in numerous
      territories that are not optimally suited for open-surgical techniques. Though
      the initial development and use of these devices was directed towards specific
      vascular beds (i.e., coronary, peripheral, cerebrovascular), it is becoming
      increasingly apparent that these devices can be effectively used in alternate
      situations when clinically indicated. We describe two cases of nontraditional
      uses of noncoronary devices (specifically biliary self-expanding stents and
      neurovascular coils) in patients with coronary artery pathology.

PMID- 19182293
TI  - Multivessel coronary artery thrombosis.
AB  - Simultaneous thrombosis of multiple epicardial coronary arteries is an uncommon
      clinical finding in ST-segment elevation myocardial infarction (STEMI). We
      describe a 37-year-old male present with inferior wall STEMI who was found to
      have large thrombi in both the right coronary artery (RCA) and the left anterior
      descending artery (LAD). We reviewed 23 patients with multivessel thrombosis in
      acute myocardial infarction in the literature. The mean age of patients was 53 +/
      14 years (32-82 years); 74% were males, and most patients had multiple risk
      factors for coronary artery disease. The LAD (78%) and RCA (87%) were the
      arteries involved for most patients. Aspiration thrombectomy was used in 3 cases.
      Though it is rare, STEMI with multiple culprit arteries can occur, and it is
      crucial to recognize this condition to determine the proper treatment, since most
      of these patients are critically ill.

PMID- 19182294
TI  - Clinical images. Invisible aortic arch vessels.

PMID- 19182295
TI  - Transcatheter closure of secundum atrial septal defect in the elderly.

PMID- 19182296
TI  - When and how should atrial septal defects be closed in adults?
AB  - In this review, evidence is presented to indicate that hemodynamically
      significant (right ventricular volume overload) atrial septal defects (ASDs) in
      adults should be transcatheter occluded, irrespective of symptomatology. While
      surgical closure is safe and effective, device closure carries less morbidity.
      Several devices have been investigated over the last few decades, but at the
      present time, only two devices, namely, the Amplatzer and the Helex, have
      received FDA approval; the former is useful in most defects, while the latter is
      useful in small- and medium-sized defects. A detailed description of Amplatzer
      device implantation is presented. Finally, approaches to occlude ASDs with
      complex anatomy are reviewed.

PMID- 19182297
TI  - An unusual thrombotic complication during percutaneous closure of atrial septal
      defect.
AB  - A case is described where intracardiac thrombus was observed at the junction of
      the superior vena cava and the right atrium during attempted closure of an atrial
      septal defect (ASD) using a device similar in design to the Amplatzer septal
      occluder (Heart R atrial septal occluder). Thrombosis was likely related to the
      multiple attempts required when deploying the device and the attendant prolonged
      procedural time. The patient underwent subsequent urgent surgical closure of the
      ASD.

PMID- 19182298
TI  - StentBoost used to guide management of a critical ostial right coronary artery
      lesion.
AB  - This report describes a case of a critical ostial lesion of a dominant right
      coronary artery (RCA) in a patient with poor left ventricular function due to a
      previous anterior infarction and documented late drug-eluting stent thrombosis of
      the RCA. The precise non-invasive determination of the proximal edge of a
      previously deployed stent by a new imaging technique, StentBoost, showed the
      lesion not only to be proximal to the stent in the uncovered ostium, but also
      restricted to the section outside the stent. This, together with the patient's
      clinical factors, suggested that stent placement was the optimal treatment
      strategy.

PMID- 19182299
TI  - A case of giant coronary artery aneurysm after placement of a heparin-coated
      stent.
AB  - The formation of coronary aneurysms and pseudoaneurysms are a rare but previously
      described complication after percutaneous coronary intervention (PCI). We present
      a unique case of the development of a giant coronary aneurysm after placement of
      a heparin-coated stent. A 79-year-old female who had PCI to the left anterior
      descending coronary artery (LAD) using a heparin-coated stent three years
      previously underwent cardiac catheterization. Coronary angiography revealed a
      giant aneurysm measuring 19 x 18 mm immediately distal to the previously
      implanted stent in the LAD. The patient refused any further intervention and was
      treated with aggressive medical management. Eighteen months have now passed, and
      the patient has been stable without further cardiac events or complaints.

PMID- 19182300
TI  - Radial artery perforation and its management during PCI.
AB  - Radial artery perforation is a rare but important complication of the transradial
      approach. This report highlights two cases of radial artery perforation during
      percutaneous coronary intervention managed by simple strategies without resorting
      to an alternative route. The guiding catheter itself helps to seal the
      perforation, hence continuing to perform the procedure through the same route is
      an effective way to seal off the perforation.

PMID- 19182301
TI  - Very late stent thrombosis after bare-metal stent implantation: case reports and
      review of the literature.
AB  - Stent thrombosis (ST) is a catastrophic complication that frequently presents as
      an acute myocardial infarction and/or death. The most recently accepted
      definition established by the Academic Research Consortium classifies ST as:
      early (occurring within 30 days), late (30 days to 1 year) or very late (after 1
      year). Very late ST has been reported following drug-eluting stent implantation
      with rates up to 0.6% per year and has been attributed to delayed strut
      endothelialization. However, very late ST is unusual after bare-metal stent (BMS)
      implantation. We report two cases of patients presenting with ST-elevation
      myocardial infarction due to very late ST 6 and 8 years after BMS implantation.

PMID- 19182302
TI  - Separate origin of major coronary arteries from the right sinus with angioplasty
      and stenting of anomalous left circumflex and left anterior descending arteries.
AB  - Coronary arteries of anomalous origin are uncommon and all three coronary
      arteries arising from a single sinus of Valsalva is very rare. Percutaneous
      coronary intervention of such arteries is technically difficult and challenging.
      We report the case of a patient with all three coronary arteries arising from the
      right sinus of Valsalva who presented with acute coronary syndrome. Coronary
      angiography showed significant stenosis of the left circumflex and left anterior
      descending coronary arteries followed by successful angioplasty and stenting of
      these arteries.

PMID- 19182303
TI  - Large mycotic pseudoaneurysm of the left circumflex treated with antibiotics and
      covered stent.
AB  - Coronary artery mycotic aneurysms are rare complications of infective
      endocarditis. They are usually managed surgically with excision of the aneurysm.
      This surgical procedure has high morbidity and mortality. We report a case of a
      giant mycotic coronary aneurysm following infective endocarditis which was
      treated with intravenous antibiotics and covered stent. This case highlights a
      new treatment modality in critically ill patients.

PMID- 19182304
TI  - Interatrial septal closure devices and aortic perforation: a note of caution.
AB  - Percutaneous defect closure is well established in patients with a symptomatic
      patent foramen ovale (PFO). Despite a safe interventional procedure, severe
      complications have been described during device implantation or follow up. Two
      patients are described whose cases may serve to warn of an unusual complication
      associated with a closure device. Several weeks after percutaneous PFO closure,
      perforation of a device strut into the aortic root was evident in both
      asymptomatic patients. The perforations were repaired surgically and both
      patients had further uneventful follow-ups. Procedures which could decrease the
      risk of device perforation should be adhered to and the indication for closure
      should consider this potential complication.

PMID- 19182305
TI  - Strategic opportunities for effective optimal prescribing and medication
      management.
AB  - BACKGROUND: Canadians receive over 422 million prescriptions and spend over $26
      billion annually on drugs. Yet, we do not systematically capture information on
      whether the right drugs reach the right people with the intended benefits, while
      avoiding unintended harm. It is important to identify and understand the
      effectiveness of approaches used to improve prescribing and medication use.
      OBJECTIVE: To discuss the medication-use system, identify factors affecting
      prescribing, and assess effectiveness of interventions. METHODS: A literature
      review was conducted using electronic databases, federal agencies', provincial
      health departments', health service delivery organizations' and Canadian health
      research organizations' websites, the Internet, and some hand searching.
      Interventions identified were categorized according to the Effective Practice and
      Organization of Care Group (EPOC) classification, with effectiveness based on the
      literature. RESULTS: Factors affecting prescribing relate to the patient and
      society, medication, prescriber, practice environment and organization, available
      information and other external factors. Interventions reported as generally
      effective are multi-faceted interventions, academic detailing, and reminders.
      Interventions reported as sometimes effective are audit and feedback or physician
      profiling, local opinion leaders, drug utilization review, and local consensus
      guidelines. Passive dissemination of educational materials is deemed generally
      ineffective. CONCLUSIONS: No single approach is appropriate for every prescribing
      problem, health professional prescriber practice or health care setting.
      Interventions to improve prescribing in community and institutional settings have
      variable effect sizes. Effectiveness is related to content, delivery mechanisms,
      intensity, intervention's context, and implementation environment. Even an
      intervention with a small effect size (< 10%) may yield important changes in drug
      use when applied on a population basis. Further research and evaluation is needed
      to determine how or why the interventions work and identify barriers to effective
      implementation.

PMID- 19182306
TI  - Child guardianship in a Canadian home visitation program for women who use
      substances in the perinatal period.
AB  - BACKGROUND: Retaining guardianship of one's infant is often a priority for
      pregnant women who use substances, and may be beneficial to infants when they are
      safe in their mothers' care. Previous studies from the United States have
      identified several maternal psychosocial characteristics associated with the
      ability to keep an infant free from abuse or neglect; however, little is known
      about the impact of multiple risk factors on guardianship, particularly in
      Canadian intervention programs. OBJECTIVE: To describe maternal characteristics
      associated with child guardianship among pregnant women at risk of an alcohol
      and/or substance exposed pregnancy who attended a Canadian home visitation
      program. METHODS: Guardianship status at 6 months post-enrolment was extracted
      from a provincial program's records for all women enrolled between November 1999
      and May 2005 (n=64). Bivariate analyses were performed to determine client
      characteristics most likely to have retained guardianship. RESULTS: At follow-up,
      70% of participants were guardians of the index infant. Higher income, more
      prenatal care, no history of sexual abuse, better alcohol and psychiatric scores,
      and fewer risk factors on a cumulative risk index were significantly associated
      with retaining guardianship at 6 month follow-up (p<0.05). CONCLUSIONS: Retaining
      child guardianship may be the greatest challenge and opportunity for women
      experiencing problems in multiple domains of their lives, including those
      associated with substance dependence. Programs targeted at women who use
      substances while pregnant may best assist mothers to retain guardianship of their
      infants by supporting clients to address the complex social and health problems
      often found in conjunction with addictions.

PMID- 19182307
TI  - Longitudinal Outcomes of GastroIntestinal symptoms in Canada (LOGIC): key factors
      for an effective patient retention in observational studies.
AB  - BACKGROUND: Longitudinal Outcomes of GastroIntestinal symptoms in Canada (LOGIC)
      is an ongoing study on irritable bowel syndrome (IBS) treatment patterns and
      health outcomes in routine Canadian clinical practice. Advancements in
      understanding IBS, a chronic multifaceted GI disorder, may be possible through
      methodical observational studies. The objective of this paper is to describe site
      recruitment techniques and extensive subject follow-up methodology used to
      facilitate a high return rate of questionnaires from this population-based study
      of subjects with IBS. METHODS: Invitation letters along with protocol synopses
      and preliminary site assessment questionnaires were faxed to potential sites
      across Canada. There were 1,556 subjects enrolled in this study from general
      practitioner sites (GP) and specialist sites (SP) in Canada. Subjects were
      compensated for the return of questionnaires reporting symptoms, quality of life,
      productivity, healthcare and resource utilization at baseline, Month 1, 3, 6, 9,
      and 12. Upon the return of questionnaires, subjects received thank you cards
      which included a reminder of the next questionnaire's due date. If subject
      questionnaires were not received within 2 weeks after the due date, the subjects
      received a reminder letter in the mail. RESULTS: The methodology in the LOGIC
      study allowed for a high patient questionnaire return rate (89%) through
      extensive subject reminders and follow-up. Subject participation throughout the
      study was not found to be linked to study site size or type (GP or SP).
      CONCLUSION: Questionnaire based observational studies may benefit from focusing
      resources on increasing questionnaire return rates to effectively maintain data
      reliability and also reduce non-response bias.

PMID- 19182308
TI  - [Annual CME conference of the IMA[Editorial]].

PMID- 19182309
TI  - [Independent media and critical thinking[Editorial]].

PMID- 19182310
TI  - [Prevalence of psychotropic drug use among elderly Icelanders living at home].
AB  - OBJECTIVE: To evaluate the prevalence of psychotropic drug use among home
      dwelling elderly Icelanders in the year 2006. MATERIALS AND METHODS: A population
      based drug utilization study using the Icelandic Medicines Registry. The study
      group consisted of Icelanders, seventy years and older living at home (8% of
      total population). Prevalence of antidepressant, neuroleptic, anxiolytic and
      hypnotic use (ATC-groups N06A, N05A, N05B, N05C) was defined as the dispension
      per 100 individuals of one or more prescriptions for these drugs within the year
      2006. For cross-national comparison we used data for 70-74 year olds in the
      Danish Registry of Medicinal Product Statistics. RESULTS: One third of all
      dispensed prescriptions in Iceland in 2006 were for people aged 70 years and
      older, and one fourth were for psychotropics. Elderly women were more likely than
      men to use psychotropics (RR=1.40 95% CI: 1.37-1.43). The prevalence of
      psychotropic use was 65.5% for women and 46.8% for men. Anxiolytics and hypnotics
      (N05B or N05C) were the most frequently used psychotropics, with a prevalence of
      58.5% for women and 40.3% for men. Antidepressants were used by 28.8 % of women
      and 18.4 % of men. Neuroleptics were used by 5%. By comparing 70-74 years old
      Icelanders and Danes, the Icelanders were 1.5 to 2.5 times more likely to receive
      any psychotropics drug in 2006. CONCLUSION: Use of psychotropics, especially
      anxiolytics and hypnotics, is common among elderly Icelanders. Comparing
      information for 70 to 74 year olds with Danes of same age, the prescribing of
      psychotropics is more frequent in Iceland.

PMID- 19182311
TI  - [Repair of distal biceps brachii tendon ruptures: long term retrospective follow
      up for two-incision technique].
AB  - INTRODUCTION: Rupture of the distal tendon of the biceps muscle is a rare injury.
      If unrepaired the patient will be left with weakness of supination of the arm and
      flexion in the elbow. Long term results for the 2-incision approach for tendon
      reinsertion are few but in this study we describe the long term, clinical,
      functional, and subjective results of surgical repair using the 2-incision method
      described by Boyd and Anderson. MATERIAL AND METHODS: All patients who were
      operated at FSA hospital during the years 1986-2000 because of rupture of the
      distal tendon of the biceps muscle were asked to participate in the study. Twelve
      of 16 patients accepted and answered the DASH questionnaire. Strength was tested
      with handheld dynamometer and ROM where measured. Radiograph was taken of the
      affected arm. RESULTS: From 1986 through 2006 we operated on 16 patients because
      of rupture of the distal biceps tendon, one female and 15 male. Mean age at the
      time of rupture was 46 years (24-53).The average follow up were seven years (1
      17). Ten of 12 patients were operated within two weeks from the injuries. No
      difference in strength was found between operated and non-operated arms. Late
      repair was associated with high DASH score and poor subjective results. Six
      patients developed heterotopic ossification but none of them developed radioulnar
      synostosis. One reoperation because entrapment of the median nerve was done.
      CONCLUSIONS: Despite heterotopic ossification and a small ROM deficit the Boyd
      and Anderson technique for repair of distal biceps ruptures yields good long term
      results in a low volume rural hospital. Early diagnosis and tendon reinsertion is
      of great importance to avoid persistent anterior elbow pain and poor subjective
      results.

PMID- 19182312
TI  - [Unilateral neglect: a review of causes, anatomical localization, theories and
      interventions].
AB  - Unilateral neglect is usually caused by right hemisphere damage from stroke,
      leading to difficulties in attending to stimuli in the left perceptual hemifield.
      As an example, a patient suffering from neglect may read only the right part of a
      word or the right part of sentences, or eat only from the right side his plate.
      Neglect is more common, and most often more severe, following infarcts in the
      right hemisphere than the left. Brain damage leading to neglect usually involves
      infarcts in the inferior parietal lobe, temporo-parietal junction and/or the
      superior temporal lobe. Most theories of the nature of neglect assume that
      neglect involves dysfunctional attentional mechanisms. Increased understanding of
      neglect has led to the development of several effective therapeutic
      interventions, where prism adaptation has received the most attention in recent
      years. This article reviews brain damage in neglect, theories of neglect,
      therapeutic methods for neglect and their possible future developments.

PMID- 19182313
TI  - [Case of the month: solitary fibrous tumor of the pleura].

PMID- 19182314
TI  - [Raiding foreign data banks].

PMID- 19182315
TI  - [The health care system during national crises and unemployment].

PMID- 19182316
TI  - [Renal cell carcinoma diagnosed at autopsy in Iceland 1971-2005].
AB  - INTRODUCTION: The incidence of renal cell carcinoma (RCC) is rising in Iceland.
      This has been attributed to increased diagnostic activity, such as abdominal
      imaging of unrelated diseases, rather than changes in the behavior of the
      disease. The aim of this study was to compare RCCs diagnosed in living patients
      and at autopsy, but also to investigate the relationship between the incidence of
      RCC and autopsy findings. MATERIAL AND METHODS: RCC found incidentally in
      individuals at autopsy was compared to patients diagnosed alive over three
      decades in Iceland (1971-2005). Stage at diagnosis and tumor histology was
      reviewed. RESULTS: 110 tumors were diagnosed at autopsy with a rate of 7.1/1000
      autopsies. When compared to patients diagnosed alive (n = 913) the mean age at
      diagnosis was higher in the autopsy group (74.4 vs. 65 yrs.) while male to female
      ratio and laterality was similar. Tumors found at autopsy were smaller (3.7 vs.
      7.3 cm), at lower stage (88% at stage I+II vs. 42%) and at lower tumor grade (85%
      at grade I+II vs. 56%). A difference, although smaller, is present when the
      autopsy detected cases are compared to only incidentally detected RCCs in living
      patients. Furthermore the autopsy detected tumors were more frequently of
      papillary cell type (21% vs. 8%). After correcting for declining autospy rate
      (>50%), a slight trend for a reduced rate of autopsy dectected RCC cases was seen
      during the last 10 years of the period but the difference was not significant.
      CONCLUSION: RCCs diagnosed at autopsy are at a lower stage and tumor grade than
      in patients diagnosed alive. The autopsy-rate is declining in Iceland with fewer
      RCCs found per autopsy. After correcting for the decline in autopsy rate, the
      rate of RCC detected at autopsy is relatively unchanged. The increase in
      incidence of RCC is therefore not explained by findings at autopsy.

PMID- 19182317
TI  - [Encapsulating peritoneal sclerosis].
AB  - The incidence of encapsulating peritoneal sclerosis in patients on peritoneal
      dialysis seems to be increasing worldwide. In Iceland, two cases of encapsulating
      peritoneal sclerosis have recently been diagnosed (cumulative incidence 1.6%).
      The patients followed a similar course; the disease was diagnosed in the wake of
      a bacterial peritonitis, steroid treatment was effective during the acute phase
      but eventually surgical treatment was needed and a successful enterolysis
      performed.

PMID- 19182318
TI  - [Diabetes type 1 in young adults: The relationship between psycho-social
      variables, glycemic control, depression and anxiety].
AB  - OBJECTIVE: The aim of the present study was to investigate whether psycho-social
      variables, for example social support and task- and emotion-oriented coping would
      predict psychological and physical well being among young adults with diabetes.
      MATERIAL AND METHODS: Participants were 56 individuals in their twenties
      suffering from type 1 diabetes. Response rate was 78%. The participants came from
      the whole of Iceland, 64.3% from the Greater Reykjavik area and 33.9% from rural
      areas. One participant did not indicate his place of residence. Self-assessment
      scales were used to assess depression, anxiety, task-, avoidance- and emotion
      oriented coping, social support and problems relating to diabetes. Additional
      information was obtained from patients' records concerning the results of blood
      glucose measurements (HbA1c). RESULTS: Good social support was related to less
      anxiety and depression and to less self-reported problems related to having
      diabetes. Emotion-oriented coping was related to not feeling well and task-
      oriented coping to feeling better. No relationship was found between psychosocial
      variables and blood glucose measurements and a limited relationship between self
      reported problems related to having diabetes and these measurements. CONCLUSIONS:
      Social support and coping are strongly related to measurements of depression,
      anxiety and problems related to having diabetes in the present age group. The
      results indicate that it is very important to teach and strengthen usage, as
      possible, of task-oriented coping instead of emotion-oriented coping. The results
      also indicate that social support is highly important for young adults with
      diabetes type 1. It is clear that friends and family have to be more involved in
      the treatment and also more educated about the disease and the importance of
      giving the right kind of support.

PMID- 19182319
TI  - [Cystic fibrosis--review].
AB  - The purpose of this paper is to give a brief overview of cystic fibrosis; its
      pathogenesis, diagnosis, treatment and prognosis. Cystic fibrosis is an autosomal
      recessive disorder, which is caused by a mutation in the CFTR protein, a chloride
      channel in epithelial cell membranes. More than 1500 mutations are known. The
      incidence is 1/2.000-3.000 in nations of European origin. The CFTR mutation
      influences the secretion and absorption by epithelium in various organs. The
      consequences are different depending on the organ, but there is a global tendency
      for obstruction of secretory glands. The primary organs affected are the
      respiratory tract, pancreas, gastrointestinal tract and sweat glands. The disease
      is most often diagnosed during the first months of life, with a common
      presentation of salty tasting sweat, failure to thrive and diverse faecal
      problems. Possible diagnostic tools are sweat test and DNA testing. Respiratory
      symptoms cause most morbidity, with chronic infections and an exaggerated
      inflammatory response. Abnormal water and electrolyte composition leads to
      thicker respiratory secretions compared to that of healthy individuals. The
      interaction of pathogens with the epithelium causes S. aureus, and later P.
      aeuruginosa, to transform into a mucoid form which is much more difficult to
      eradicate with antibiotics, making them a significant part of the disease burden
      of cystic fibrosis. The main respiratory medications are antibiotics,
      bronchodilators, mucolytic agents and anti-inflammatory agents. 90% of cystic
      fibrosis patients have pancreas insufficiency which is treated with pancreas
      enzymes. A good nutritional status is a necessary basis for any further
      treatment. The prognosis of cystic fibrosis patients has improved greatly over
      the last few decades in parallel with increased knowledge, and the average
      survival is currently 37 years in the United States.

PMID- 19182320
TI  - Semi-empirical formulation of multiple scattering for the Gaussian beam model of
      heavy charged particles stopping in tissue-like matter.
AB  - Dose calculation for radiotherapy with protons and heavier ions deals with a
      large volume of path integrals involving a scattering power of body tissue. This
      work provides a simple model for such demanding applications. There is an
      approximate linearity between RMS end-point displacement and range of incident
      particles in water, empirically found in measurements and detailed calculations.
      This fact was translated into a simple linear formula, from which the scattering
      power that is only inversely proportional to the residual range was derived. The
      simplicity enabled the analytical formulation for ions stopping in water, which
      was designed to be equivalent with the extended Highland model and agreed with
      measurements within 2% or 0.02 cm in RMS displacement. The simplicity will also
      improve the efficiency of numerical path integrals in the presence of
      heterogeneity.

PMID- 19182321
TI  - Ultra fast electromagnetic field computations for RF multi-transmit techniques in
      high field MRI.
AB  - A new, very fast, approach for calculations of the electromagnetic excitation
      field for MRI is presented. The calculation domain is divided in different
      homogeneous regions, where for each region a general solution is obtained by a
      summation of suitable basis functions. A unique solution for the electromagnetic
      field is found by enforcing the appropriate boundary conditions between the
      different regions. The method combines the speed of an analytical method with the
      versatility of full wave simulation methods and is validated in the pelvic region
      against FDTD simulations at 3 and 7 T and measurements at 3 T. The high speed and
      accurate reproduction of measurements and FDTD calculations are believed to offer
      large possibilities for multi-transmit applications, where it can be used for on
      line control of the global and local electric field and specific absorption rate
      (SAR) in the patient. As an example the method was evaluated for RF shimming with
      the use of 7 T simulation results, where it was demonstrated that the magnetic
      excitation field could be homogenized, while both the local and average SAR were
      reduced by 38% or more.

PMID- 19182322
TI  - Limitations of calculating field distributions and magnetic susceptibilities in
      MRI using a Fourier based method.
AB  - A discrete Fourier based method for calculating field distributions and local
      magnetic susceptibility in MRI is carefully studied. Simulations suggest that the
      method based on discrete Green's functions in both 2D and 3D spaces has less
      error than the method based on continuous Green's functions. The 2D field
      calculations require the correction of the 'Lorentz disk', which is similar to
      the Lorentz sphere term in the 3D case. A standard least-squares fit is proposed
      for the extraction of susceptibility for a single object from MR images.
      Simulations and a phantom study confirm both the discrete method and the
      feasibility of the least-squares fit approach. Finding accurate susceptibility
      values of local structures in the brain from MR images may be possible with this
      approach in the future.

PMID- 19182323
TI  - Simulation studies of a new 'OpenPET' geometry based on a quad unit of detector
      rings.
AB  - We have proposed an 'OpenPET' geometry which consists of two detector rings of
      axial length W each axially separated by a gap G. In order to obtain an axially
      continuous field-of-view (FOV) of 2W+G, the maximum limit for G must be W.
      However, two valleys of sensitivity appear, one on each side of the gap. In
      practice, the gap should be G<W in order to compensate for the sensitivity
      valleys. In this paper, we proposed an alternative method to improve uniformity
      of the sensitivity while maintaining the gap. The proposed geometry consisted of
      four units of detector rings obtained by dividing each right and left unit of
      detector rings into two units. The inner two units formed the main gap, and the
      outer two units were appropriately placed to improve the uniformity of
      sensitivity. The geometry was optimized to minimize the standard deviation of the
      sensitivity distribution. Numerical simulation results supported the
      effectiveness of the proposed method. The outer units compensated for the
      sensitivity valleys on both sides of the main gap. A more appropriate geometry
      should be designed for the desired application, such as a long axial FOV PET and
      in-beam PET.

PMID- 19182324
TI  - Bolus-tracking arterial spin labelling: theoretical and experimental results.
AB  - Arterial spin labelling (ASL) is a magnetic resonance imaging (MRI) technique
      that can be used to provide a quantitative assessment of cerebral perfusion.
      Despite the development of a number of theoretical models to facilitate
      quantitative ASL, some key challenges still remain. The purpose of this study is
      to develop a novel quantitative ASL method based on a macroscopic model that
      reduces the number of variables required to describe the physiological processes
      involved. To this end, a novel Fokker-Planck equation consisting of
      stochastically varying macroscopic variables was derived from a general Langevin
      equation. ASL data from the rat brain was acquired using a bolus-tracking ASL
      protocol where a bolus of labelled spins flowing from an inversion plane in the
      neck into an imaging plane in the brain can be observed. Bolus durations of 1.5
      s, 2.0 s and 3.0 s were used and the solution to the Fokker-Planck equation for
      the boundary conditions of bolus-tracking ASL was fitted to the experimental data
      using a least-squares fit. The mean transit time (MTT) and capillary transit time
      (CTT) were calculated from the first and second moments of the resultant curve
      respectively and the arterial transit time (ATT) was calculated by subtracting
      the CTT from the MTT. The average MTT, CTT and ATT values were 1.75 +/- 0.22 s,
      1.43 +/- 0.12 s and 0.32 +/- 0.04 s respectively. In conclusion, a new ASL
      protocol has been developed by combining the theoretical model with ASL
      experiments. The technique has the unique ability to provide solutions for
      varying bolus volumes and the generality of the new model is demonstrated by the
      derivation of additional solutions for the continuous and pulsed ASL (CASL and
      PASL) techniques.

PMID- 19182325
TI  - Linear and nonlinear elasticity imaging of soft tissue in vivo: demonstration of
      feasibility.
AB  - We establish the feasibility of imaging the linear and nonlinear elastic
      properties of soft tissue using ultrasound. We report results for breast tissue
      where it is conjectured that these properties may be used to discern malignant
      tumors from benign tumors. We consider and compare three different quantities
      that describe nonlinear behavior, including the variation of strain distribution
      with overall strain, the variation of the secant modulus with overall applied
      strain and finally the distribution of the nonlinear parameter in a fully
      nonlinear hyperelastic model of the breast tissue.

PMID- 19182326
TI  - Dietary iron-loaded rat liver haemosiderin and ferritin: in situ measurement of
      iron core nanoparticle size and cluster structure using anomalous small-angle X
      ray scattering.
AB  - The morphology, particle size distribution and cluster structure of the hydrated
      iron(III) oxyhydroxide particles associated with haemosiderin and ferritin in
      dietary iron-loaded rat liver tissue have been investigated using transmission
      electron microscopy (TEM) and anomalous small-angle x-ray scattering (ASAXS). Rat
      liver tissue was removed from a series of female Porton rats which had been fed
      an iron-rich diet until sacrifice at various ages from 2-24 months. Hepatic iron
      concentrations ranged from 1 to 65 mg Fe g(-1) dry tissue. TEM studies showed
      both dispersed and clustered iron-containing nanoparticles. The dispersed
      particles were found to have mean sizes (+/-standard deviation) of 54 +/- 8 A for
      the iron-loaded animals and 55 +/- 7 A for the controls. Superposition of
      particles in TEM images prevented direct measurement of nanoparticulate size in
      the clusters. The ASAXS data were modelled to provide a quantitative estimate of
      both the size and spacing of iron oxyhydroxide particles in the bulk samples. The
      modelling yielded close-packed particles with sizes of 60 to 78 A which when
      corrected for anomalous scattering suggests sizes from 54 to 70 A. Particle size
      distributions are of particular importance since they determine the surface iron
      to core iron ratios, which in turn are expected to be related to the molar
      toxicity of iron deposits in cells.

PMID- 19182327
TI  - Characterization of a novel phantom for three-dimensional in vitro cell
      experiments.
AB  - A novel intensity-modulated radiation therapy (IMRT) phantom for use in three
      dimensional in vitro cell experiments, based on a commercially available system
      (CIRS Inc., Norfolk, VA), was designed and fabricated. The water-equivalent
      plastic phantom can, with a set of water-equivalent plastic inserts, enclose 1-3
      multi-well tissue culture plates. Dosimetry within the phantom was assessed using
      thermoluminescence dosimeters (TLDs) and film. The phantom was loaded with three
      tissue culture plates, and an array of TLDs or a set of three films was placed
      underneath each plate within the phantom, and then irradiated using an IMRT plan
      created for it. Measured doses from each dosimeter were compared to those
      acquired from the treatment planning system. The percent differences between TLD
      measurements and the corresponding points in the treatment plan ranged from 1.3%
      to 2.9%, differences which did not show statistical significance. Average point
      by-point percent dose differences for each film plane ranged from 1.6% to 3.1%.
      The percentage dose difference for which 95% of the points in the film matched
      those corresponding to the calculated dose plane to within 3.0% ranged from 2.8%
      to 4.2%. The good agreement between predicted and measured dose shows that the
      phantom is a useful and efficient tool for three-dimensional in vitro cell
      experiments.

PMID- 19182328
TI  - Effect of rice-cooking water to the daily arsenic intake in Bangladesh: results
      of field surveys and rice-cooking experiments.
AB  - The effect of rice-cooking water to the daily arsenic intake of Bangladeshi
      people was investigated. At the first field survey, uncooked rice and cooked rice
      of 29 families were collected. Their arsenic concentrations were 0.22+/-0.11 and
      0.26+/-0.15 mg/kg dry wt, respectively. In 15 families, arsenic concentration in
      rice increased after cooking. Good correlation (R(2)=0.89) was observed between
      arsenic in rice-cooking water and the difference of arsenic concentration in rice
      by cooking. In the second survey, we collected one-day duplicated food of 18
      families. As a result, we estimated that six of 18 families likely used the
      arsenic contaminated water for cooking rice even they drank less arsenic
      contaminated water for drinking purpose. We also conducted rice-cooking
      experiments in the laboratory, changing arsenic concentration in rice-cooking
      water. Clear linear relationships were obtained between the arsenic in rice
      cooking water and the difference of arsenic concentration in rice by cooking.
      Factors that affect arsenic concentration in cooked rice are suggested as
      follows: (1) arsenic concentration in uncooked rice, (2) that in rice-cooking
      water, (3) difference in water content of rice before and after cooking, and (4)
      types of rice, especially, the difference between parboiled and non-parboiled
      rice.

PMID- 19182329
TI  - Variability analysis of pathogen and indicator loads from urban sewer systems
      along a river.
AB  - The pathogen loads within surface waters originating from urban wastewater
      sources needs to be assessed to support drinking water risk estimations and
      optimal selection of risk reduction measures. Locally reported discharges from
      sewer systems (>100,000 persons connected) were used to simulate the potential
      microbial loads into the Gota alv river, Sweden. Using Monte Carlo simulations,
      the median and 95% percentile (i.e. worst case) of total microbial load from
      wastewater treatment plants, sewer network overflows and emergency discharges
      were assessed and presented for dry and wet weather conditions. Wastewater
      treatment plants with secondary treatment represented a major source of E. coli,
      norovirus, Giardia and Cryptosporidium. During wet weather, comparably high
      microbial loads were found for sewer overflows due to heavy rains. Substantial
      loads were also associated with an incident of the emergency discharge of
      untreated wastewater. Simulated river water concentrations of faecal indicators
      (E. coli, sulfite reducing clostridia, somatic coliphages) and pathogens
      (norovirus, Giardia, Cryptosporidium) were confirmed by river sampling data,
      suggesting that urban wastewater is the major microbial source for this river.

PMID- 19182330
TI  - Using treated wastewater to save wetlands impacted by climate change and pumping.
AB  - Wetlands occur where the watertable which underlies much of Perth intersects the
      land surface. Regional groundwater levels have been falling since the 1970s as a
      result of lower rainfall and increased extraction causing a loss of environmental
      and social values. This paper examines a scheme to add almost 2 GL/yr of treated
      wastewater to infiltration galleries immediately down-gradient of Perry Lakes so
      that the wetlands may be restored. Modelling suggest that groundwater levels
      would be raised up-gradient of the galleries, increasing both lake levels and
      groundwater supplies in the vicinity. It is not envisaged that wastewater will
      enter the lakes. Adding treated wastewater to nearby trial galleries has shown
      that phosphorus, pathogens and organic carbon are greatly reduced within 5 to 50
      m. Nitrogen levels are less reduced but are similar to those in the lakes and
      nearby aquifer. It is estimated that the wetlands add about $54 m to land prices
      near the lakes and would add more than $24M to the sale price of proposed nearby
      land if they contain water. If successful, the proposal could be a test case for
      the use of treated wastewater to create hydraulic barriers against salt water
      intrusion into coastal areas.

PMID- 19182331
TI  - Microbial ecology and performance of ammonia oxidizing bacteria (AOB) in
      biological processes treating petrochemical wastewater with high strength of
      ammonia: effect of Na(2)CO(3) addition.
AB  - This study evaluated nitrification performance and microbial ecology of AOB in a
      full-scale biological process, powder activated carbon treatment (PACT), and a
      pilot-scale biological process, moving bed biofilm reactor (MBBR), treating
      wastewater collected from a petrochemical industry park. The petrochemical
      influent wastewater characteristics showed a relative low carbon to nitrogen
      ratio around 1 with average COD and ammonia concentrations of 310 mg/L and 325 mg
      N/L, respectively. The average nitrification efficiency of the full-scale PACT
      process was around 11% during this study. For the pilot-scale MBBR, the average
      nitrification efficiency was 24% during the Run I operation mode, which provided
      a slightly better performance in nitrification than that of the PACT process.
      During the Run II operation, the pH control mode was switched from addition of
      NaOH to Na(2)CO(3), leading to a significant improvement in nitrification
      efficiency of 51%. In addition to a dramatic change in nitrification performance,
      the microbial ecology of AOB, monitored with the terminal restriction fragment
      length polymorphism (T-RFLP) molecular methodology, was found to be different
      between Runs I and II. The amoA-based TRFLP results indicated that Nitrosomonas
      europaea lineage was the dominant AOB population during Run I operation, while
      Nitrosospira-like AOB was dominant during Run II operation. To confirm the
      effects of Na(2)CO(3) addition on the nitrification performance and AOB microbial
      ecology observed in the MBBR process, batch experiments were conducted. The
      results suggest that addition of Na(2)CO(3) as a pH control strategy can improve
      nitrification performance and also influence AOB microbial ecology as well.
      Although the exact mechanisms are not clear at this time, the results showing the
      effects of adding different buffering chemicals such as NaOH or Na(2)CO(3) on AOB
      populations have never been demonstrated until this study.

PMID- 19182332
TI  - Pollutant removal within hybrid constructed wetland systems in tropical regions.
AB  - Hybrid constructed wetlands have received tremendous interests for water quality
      enhancement due to insufficient sewage treatment and groundwater deterioration in
      Taiwan. The main objectives of this study were to investigate pollutant removal
      efficiencies and mechanisms within field-scale hybrid natural purification
      systems. The studied hybrid constructed wetland systems include an oxidation
      pond, two serial surface flow wetlands with a cascade in between, and a
      subsurface flow wetland receiving secondary treated dormitory sewage. The average
      SS, BOD and COD percent removal efficiency was 86.7, 86.5 and 57.8%,
      respectively. The ratio of BOD to COD decreased from 0.65 in the initial aerobic
      compartment to 0.21 in anoxic parts of the systems, indicating most biological
      degradable materials were decomposed in the aerobic oxidation pond and surface
      flow wetlands. Heavy metal removal percentages of copper and zinc were 72.9 and
      68.3%, respectively. Sedimentation and plant uptake are the possible sinks for
      metals retention. Significant phosphorus removal was not achieved in this study.
      Total Kjeldahl nitrogen (TKN) and ammonium decreased from 4.08 to 1.43 and 3.74
      to 1.21 mg/L, respectively, while nitrate nitrogen increased from 1.91 to 3.85
      mg/L within the aerobic oxidation pond and surface flow wetlands. This result
      demonstrated nitrification occurring within aerobic compartments. The nitrate
      nitrogen continued to decrease from 3.85 to 1.43 mg/L within the anoxic
      subsurface wetlands mainly through denitrification transformation. Total nitrogen
      removal was from 7.61 to 3.61 mg/L, with the percentage removal of total nitrogen
      around 52.6%. The primary nitrogen removal and transformation mechanisms within
      the studied wetland systems were nitrification within aerobic followed by
      denitrificaiton within anaerobic systems. The emergent macrophytes enhance
      aeration through oxygen transferring that attributing the higher organic matter
      removal and nitrification rate. The hybrid wetland systems are viable options of
      pollutants transformation and removal in tropical countries, while tertiary
      wastewater systems are too costly or unable to operate. Effluent of purified
      systems can comply with local surface water criteria rendering for groundwater
      recharge.

PMID- 19182333
TI  - Biosolids odor reduction by solids inventory management in the secondary
      activated sludge treatment system.
AB  - A wastewater treatment plant consists of unit processes designed to achieve
      specific waste reduction goals. Offensive odors associated with these treatment
      processes are a constant source of public complaints. The purpose of this study
      was to statistically determine the process parameters that influence the
      formation of volatile sulfur compounds (VSCs) in the secondary treatment system.
      A statistical model was developed to relate the process parameters to the
      formation of VSCs in this system. The model established that F/M ratio, sludge
      blanket depth and SSV(60) were the dominant process parameters that influenced
      the formation of VSCs in the secondary sedimentation basin. This model provides a
      useful tool for plant engineers to predict and control the VSC formation in a
      secondary activated sludge treatment system.

PMID- 19182334
TI  - Evaluation of appropriate technologies for grey water treatments and reuses.
AB  - As water is becoming a rare resource, the onsite reuse and recycling of grey
      water is practiced in many countries as a sustainable solution to reduce the
      overall urban water demand. However, the lack of appropriate water quality
      standards or guidelines has hampered the appropriate grey water reuses. Based on
      literature review, a non-potable urban grey water treatment and reuse scheme is
      proposed and the treatment alternatives for grey water reuse are evaluated
      according to the grey water characteristics, the proposed standards and
      economical feasibility.

PMID- 19182335
TI  - Biodegradation of 17alpha-methyltestosterone and isolation of MT-degrading
      bacterium from sediment of Nile tilapia masculinization pond.
AB  - The fast growing and highly tolerant fish Nile tilapia is one of the most
      commonly raised fish in the aquaculture industry. To produce an all-male
      population, a common practice is to feed the Nile tilapia fry with 17alpha
      methyltestosterone (MT)-impregnated food. Uneaten fish food with MT may
      accumulate in the masculinization ponds and be released into the receiving
      waters. Not much is known about the fate of MT in the fish farms and in the
      receiving streams. The objective of this study is to investigate the
      biodegradation of MT under aerobic condition and to isolate responsible
      microorganisms. Aerobic biodegradation tests were conducted with MT
      concentrations of 0.3, 1.0, 5.0, 7.0, and 10.0 mg/L using sediment from the
      masculinization pond as microbial seed. The results suggested that MT is
      biodegradable. Lag phase was not observed in all cases. With initial
      concentrations of 0.3, 1.0, 5.0, 7.0, and 10.0 mg/l, the first-order degradation
      rates were 0.52, 0.23, 0.17, 0.13 and 0.10 day(-1), respectively. Degradation
      rates were found to decrease with an increase in the initial MT concentration.
      Analysis of 16S rRNA gene sequences of a strain isolated from the sediment
      indicated that the strain was highly similar to Pimelobacter simplex strain S151
      (100%) which is in the genus Nocardioidaceae. Using this strain, MT is degraded
      with a first-order degradation rate of 0.044 h(-1) excluding the lag phase. This
      is the first work reporting biodegradation of MT and isolation of MT-degrading
      bacterium from environment.

PMID- 19182336
TI  - Improved control of multiple-antibiotic-resistance-related microbial risk in
      swine manure wastes by autothermal thermophilic aerobic digestion.
AB  - In this study, we microbiologically evaluated antibiotic resistance and
      pathogenicity in livestock (swine) manure as well as its biologically stabilized
      products. One of new livestock manure stabilization techniques is ATAD
      (Autothermal Thermophilic Aerobic Digestion). Because of its high operation
      temperature (60-65 degrees C), it has been speculated to have effective microbial
      risk control in livestock manure. This hypothesis was tested by evaluating
      microbial risk in ATAD-treated swine manure. Antibiotic resistance, multiple
      antibiotic resistance (MAR), and pathogenicity were microbiologically examined
      for swine manure as well as its conventionally stabilized (anaerobically
      fermented) and ATAD-stabilized products. In the swine manure and its
      conventionally stabilized product, antibiotic resistant (tetracycline-,
      kanamycine-, ampicillin-, and rifampicin-resistant) bacteria and the pathogen
      indicator bacteria were detected. Furthermore, approximately 2-5% of the
      Staphylococcus and Salmonella colonies from their selective culture media were
      found to exhibit a MAR-phenotypes, suggesting a serious level of microbe induced
      health risk. In contrast, after the swine manure was stabilized with a pilot
      scale ATAD treatment for 3 days at 60-65 degrees C, antibiotic resistant
      bacteria, pathogen indicator bacteria, and MAR-exhibiting pathogens were all
      undetected. These findings support the improved control of microbial risk in
      livestock wastes by ATAD treatment.

PMID- 19182337
TI  - Biodegradation of phenol by aerobic granulation technology.
AB  - High organic load and fluctuation in organic load in terms of total phenols is
      fed into a SBR of higher height and diameter ratio (H/D 20) and operated at 4 h
      cycle basis with a volumetric exchange ratio of 50% resulting in a constant HRT
      of 8 h. Successful cultivation of aerobic granules was achieved. Aerobic
      granulation technology system withstands the inhibitory effect as well as
      fluctuation of organic load and a better efficiency as compared to traditional
      activated sludge process. Maximum phenol concentration of 650 mg l(-1) is treated
      efficiently in 4 h which is equal to an organic load of 3.9 kg m(-3) d(-1). After
      granulation the effluent phenol and COD concentrations were 3 mg l(-1) and 41 mg
      l(-1) respectively. Phenol removal efficiency and COD removal efficiency of 94%
      and 95% were achieved. Effluent O.D.(600) stabilizes at 0.15 which corresponds to
      minimum loss of biomass, which is the main advantage of SBR.

PMID- 19182338
TI  - Improving the success of bottom-up development work by acknowledging the dynamics
      among stakeholders: a case study from an Engineers Without Borders water supply
      project in Tenganan, Indonesia.
AB  - This paper presents a model of development action synthesising the development
      arena framework with collective action theory. It shows how application of this
      model in the Engineers Without Borders Australia (EWB) water supply improvement
      and capacity building project in Tenganan, Indonesia has helped to maximise the
      extent to which the project practice can reflect the project rhetoric as "bottom
      up" or community-inspired. The model posits a broad range of stakeholders
      actively engaged in development action: each stakeholder is different, with its
      own interests, missions, procedures, and ways of deploying power in development
      action. Recognising the multiplicity of subjects of development is especially
      crucial for improving bottom-up practice. Connections and interactions among
      stakeholders are inherently problematic, and must be negotiated to accomplish
      development work, as tensions in the dynamic among stakeholders may operate to
      restrict the success of these "bottom-up" development projects.

PMID- 19182339
TI  - Recovery of heavy metals from industrial sludge using various acid extraction
      approaches.
AB  - Heavy metals were removed from industrial sludge by traditional and microwave
      assisted acid extraction approaches. The effects of acid concentration,
      extraction time, sludge particle size and solid/liquid (S/L) ratio on copper
      extraction efficiency were assessed. Leaching with increased acid concentrations
      increased the yield of heavy metals from the industrial sludge. In microwave
      assisted acid extraction, reducing the S/L ratio and sludge particle size
      increased copper-extraction efficiency. These experimental findings indicate that
      S/L ratio most strongly influenced microwave-assisted acid extraction. Both
      traditional and microwave-assisted acid extraction demonstrate that sulfuric acid
      was an effective extractant, and the copper fraction in extracted sludge shifted
      from being primarily bound to Fe-Mn oxides and organic-matter partition, to being
      mostly bound to organic matter, remaining as a residue during acid extraction.

PMID- 19182340
TI  - Evaluation of extremely shallow vertical subsurface flow constructed wetland for
      nutrient removal.
AB  - Mesocosm-scale vertical subsurface flow constructed wetlands (SSF, 0.5 m length,
      0.3 m width) with different reed-bed thickness, including standard SSF (SD, 0.6 m
      deep), shallow SSF (S, 0.3 m deep) and extremely shallow SSF (ES, 0.075 m deep)
      were set up at sewage treatment plant and their nutrient removal efficiencies
      from the sewage plant effluent were compared under three hydraulic loading rate
      (HLR) conditions of 0.15, 0.45 and 0.75 m(3) m(-2) d(-1). A very interesting
      characteristics was found for the extremely shallow SSF, in which a high nitrogen
      removal efficiency was obtained despite the effective hydraulic retention time
      was only 1/8 times as long as the standard SSF. The results of kinetic analysis
      confirmed that the high volumetric nitrogen removal efficiency observed in the
      extremely shallow SSF did not depend on high response against the water
      temperature but on much higher basic nitrogen removal activity compared with
      other SSF. The phosphorus removal depending on the adsorption to sand in the reed
      bed filter was, however, the lowest in the extremely shallow SSF although the
      volumetric removal efficiency was much higher compared with other SSF. Results of
      morphological analysis of rhizosphere collected from respective reed-bed
      suggested that the extremely shallow SSF lead to a very high-density rhizosphere,
      resulting in a high basic nitrogen removal activity and volumetric phosphorus
      removal efficiency.

PMID- 19182342
TI  - Using reclaimed water as make-up water for a district heating system: a case
      study in Beijing.
AB  - Make-up water used for a district heating system in Beijing is about 63
      kg/m(2).a, so the total quantity of make-up water is over 10 million m(3) per
      year. Water deficiency is very serious in Beijing. Using reclaimed water as make
      up water is one of the important measures to relieve water crises of the city.
      This study is mainly on nanofiltration (NF) process. The reclaimed water for the
      experiment is the effluent of The Sixth Water Plant, an urban reclaimed water
      plant in Beijing. Micro-filter (MF) and activated carbon filtration are used as
      pretreatment units to eliminate turbidity, organic matter in reclaimed water to
      avoid contamination and scale on the surface of NF membrane. Four SAEHAN NE-90
      membrane elements with an array of 2-1-1 are selected for the NF unit and the
      flow rate is controlled around 1 m(3)/h. Through the test, it has been verified
      that NF membrane has high removal rate to the salt and impurity of reclaimed
      water. The average salt removal rate of the system is more than 94%, while the
      rejections of bivalent ions are more than 98%. The removal rates of organic
      matter, NH(3)-N and TP are 77%, 96% and 84% respectively. Temperature is a main
      influence of the process. When temperature is increasing, the permeate flux is
      increasing as well. The operating pressure is an important factor effecting
      membrane flux also. By the data comparison it is confirmed that the appropriate
      operating pressure and the water recovery of NF system are 0.75 MPa and 63.5%
      respectively.

PMID- 19182341
TI  - Competitive adsorption of heavy metals in soil underlying an infiltration
      facility installed in an urban area.
AB  - Accumulation of heavy metals at elevated concentration and potential of
      considerable amount of the accumulated heavy metals to reach the soil system was
      observed from earlier studies in soakaways sediments within an infiltration
      facility in Tokyo, Japan. In order to understand the competitive adsorption
      behaviour of heavy metals Zn, Ni and Cu in soil, competitive batch adsorption
      experiments were carried out using single metal and binary metal combinations on
      soil samples representative of underlying soil and surface soil at the site.
      Speciation analysis of the adsorbed metals was carried out through BCR sequential
      extraction method. Among the metals, Cu was not affected by competition while Zn
      and Ni were affected by competition of coexisting metals. The parameters of
      fitted 'Freundlich' and 'Langmuir' isotherms indicated more intense competition
      in underlying soil compared to surface soil for adsorption of Zn and Ni. The
      speciation of adsorbed metals revealed less selectivity of Zn and Ni to soil
      organic matter, while dominance of organic bound fraction was observed for Cu,
      especially in organic rich surface soil. Compared to underlying soil, the surface
      soil is expected to provide greater adsorption to heavy metals as well as provide
      greater stability to adsorbed metals, especially for Cu.

PMID- 19182343
TI  - Evaluation of biodegradation potential of organic compounds by river water
      microorganisms.
AB  - The aim of this study was to assess the availability of the biodegradation
      potential of aniline and phenol as the indicator for evaluating pollutant impact
      on a river environment. Biodegradation tests employing river water microorganisms
      were carried out by a modified TOC-Handai method using aniline and phenol as
      substrates. Complete degradation time and half-life were determined as indicators
      expressing the biodegradation potential of aniline and phenol, respectively.
      Investigations in Lake Biwa-Yodo River basin for more than two years showed that
      the biodegradation potential of both compounds varied seasonally. In addition,
      aniline biodegradation potential seemed to be influenced by the hydraulic
      retention time at each sampling station, while downstream stations with large
      input of wastewater from the surrounding cities were divided from upstream
      stations by phenol biodegradation potential. Comparison of the biodegradation
      potential in rivers at different pollution levels also showed that polluted and
      less polluted rivers were clearly divided by phenol biodegradation potential.
      These results indicated that phenol biodegradation potential can be applied as an
      indicator for evaluating the soundness of river environment from the view point
      of ecological function.

PMID- 19182344
TI  - Infrastructure optimisation via MBR retrofit: a design guide.
AB  - Wastewater management is continually evolving with the development and
      implementation of new, more efficient technologies. One of these is the Membrane
      Bioreactor (MBR). Although a relatively new technology in Australia, MBR
      wastewater treatment has been widely used elsewhere for over 20 years, with
      thousands of MBRs now in operation worldwide. Over the past 5 years, MBR
      technology has been enthusiastically embraced in Australia as a potential
      treatment upgrade option, and via retrofit typically offers two major benefits:
      (1) more capacity using mostly existing facilities, and (2) very high quality
      treated effluent. However, infrastructure optimisation via MBR retrofit is not a
      simple or low-cost solution and there are many factors which should be carefully
      evaluated before deciding on this method of plant upgrade. The paper reviews a
      range of design parameters which should be carefully evaluated when considering
      an MBR retrofit solution. Several actual and conceptual case studies are
      considered to demonstrate both advantages and disadvantages. Whilst optimising
      existing facilities and production of high quality water for reuse are powerful
      drivers, it is suggested that MBRs are perhaps not always the most sustainable
      Whole-of-Life solution for a wastewater treatment plant upgrade, especially by
      way of a retrofit.

PMID- 19182345
TI  - Comparative assessment of gene quantification using real-time PCR and water
      quality parameters in unsanitary landfill.
AB  - Because of increasing demanding for development of direct ecological landfill
      monitoring methods, there is a requirement for the condition of landfills and
      their influence on the environment to be characterized by the behavior of enzymes
      and bacteria mainly concerned with biochemical reaction in the landfills. This
      study was thus conducted to understand the fates of contaminants in association
      with groundwater quality parameters. For the study, groundwater was seasonally
      sampled from four closed unsanitary landfills in which microbial diversity was
      simultaneously obtained by 16S rDNA methods. Subsequently, a number of the
      specific genes of representative bacteria and encoding enzymes were quantified by
      real-time PCR. The relationship between water quality parameters and gene
      quantification were compared based on correlation factors. Correlation between
      DSR gene and BOD was greater than 0.8 while NSR gene and nitrate were related
      more than 0.9. For MTOT, it was at the highest related at 100% over BOD/COD and
      Dde genes were correlated over 0.8. In addition, anaerobic genes and DO were also
      related more than 0.8, showing anaerobic reactions generally dependent upon DO.
      As demonstrated in the study, molecular biological investigation and water
      quality parameters are highly co-linked, so that quantitative real-time PCR could
      be cooperatively used for assessing landfill stabilization in association with
      the conventional monitoring parameters.

PMID- 19182346
TI  - Differences in adsorption mechanisms of heavy metal by two different plant
      biomasses: reed and brown seaweed.
AB  - The adsorption of Pb(II) by two different biomaterials, reed (Phragmites
      australis) and brown seaweed (Sargassum horneri) biomass pretreated with CaCl(2),
      were compared in an attempt to explain the differences in adsorption performance
      between the two biosorbents. A very interesting characteristic was found in their
      individual adsorption performances; the Pb(II) adsorption capacity of brown
      seaweed (Q(max)=0.45 mmol/g) was much higher than that of reed (Q(max)=0.05
      mmol/g), but its adsorption affinity (b=112 L/mmol) was much lower compared with
      that of reed (b=471 L/mmol). To elucidate the mechanism, the elemental
      components, ion exchange phenomenon and roles of functional groups of these two
      biosorbents were compared. The higher Pb(II) adsorption by brown seaweed could be
      due to its richness in total functional groups and calcium contents on its
      surface. In contrast, the functional complexity, higher zeta potential and pK(a)
      value (deprotonation state) of reed are believed to lead to its high adsorption
      affinity.

PMID- 19182347
TI  - A novel laboratory cultivation method to examine antibiotic-resistance-related
      microbial risks in urban water environments.
AB  - Although microbial risk due to antibiotic-resistant microbes in water has been a
      serious public health concern, the current culture-dependent detecting methods
      using nutrient-rich conditions may not be suitable for evaluating microbial risk.
      In the present study, a novel cultivation method was developed to detect
      antibiotic-resistant microbes at various nutrient levels. A nutrient-rich medium
      Luria-Bertani broth (LB) was diluted at a wide range of dilution factors (10(0)
      10(4)) and amended with either tetracycline or vancomycin. A standard
      environmental cultivation medium, R2A, was also used by amending with
      antibiotics. The diluted LB with antibiotics was able to detect previously known
      oligotrophic and antibiotic-resistant bacteria in drinking water and swine manure
      samples, respectively. These results validate the capability of the new method to
      detect antibiotic-resistant microbes in various environmental water samples.
      Using the developed method in assessing microbial risk due to antibiotic
      resistant microbes in river and municipal wastewater plants, we found that the
      viable counts and antibiotic resistance fraction were significantly influenced by
      the type and concentration level of antibiotic exposure and the cultivation
      medium conditions. This suggests a further need to standardize cultivation method
      procedures, to assess microbial risk in water samples.

PMID- 19182348
TI  - Economic analysis in the process of the preparation of river basin management
      plans in Slovenia: the Drava River Basin pilot study.
AB  - According to the EU Directive 2000/60/EC (Water Framework Directive, hereinafter
      called: WFD), several steps have to be worked out on the way towards the good
      water status. For this goal, some of the main elements of the river basin
      management plans are the programme of measures. The programme of measures has to
      include basic and supplementary measures. In addition, it has to check the
      implementation of European Directives into the national law and has to estimate
      the effects of these rules on the quality of the water bodies. If these
      regulations are not sufficient to reach the good status of water, supplementary
      measures have to be applied. The paper gives an overview of how basic and
      supplementary measures for wastewater treatment were considered in the Drava
      River Basin. The main stress is given to the implementation of the EU Directive
      91/271/EEC (the Urban Waste Water Treatment Directive, hereinafter called:
      UWWTD), as part of the basic measures as defined in Annex VI of WFD and its
      results in the Drava River Basin.

PMID- 19182349
TI  - Who has to pay for measures in the field of water management? A proposal for
      applying the polluter pays principle.
AB  - There is no doubt about the fact that the implementation of the European Water
      Framework Directive (WFD) and the pursuit of its goal of good ecological status
      will give rise to measures in different fields of water management. However, a
      conclusive and transparent method of financing these measures is still missing up
      to now. Measures in the water management sector are no mere end in themselves;
      instead, they serve specific ends directed at human activities or they serve
      general environment objectives. Following the integrative approach of the WFD on
      looking upon river basins as a whole and its requirement to observe the polluter
      pays principle, all different groups within a river basin should contribute to
      the costs according to their cost-bearer roles as polluters, stakeholders with
      vested interests or beneficiaries via relevant yardsticks. In order to quantify
      the financial expenditure of each cost bearer, a special algorithm was developed
      and tested in the river basin of a small tributary of the Ruhr River. It was
      proved to be generally practicable with regard to its handling and the
      comprehension of the results. Therefore, the application of a cost bearer system
      based on the polluter-pays principle and thus in correspondence with the WFD's
      requirements should appear possible in order to finance future measures.

PMID- 19182350
TI  - An implementation framework for wastewater treatment models requiring a minimum
      programming expertise.
AB  - Mathematical modelling in environmental biotechnology has been a traditionally
      difficult resource to access for researchers and students without programming
      expertise. The great degree of flexibility required from model implementation
      platforms to be suitable for research applications restricts their use to
      programming expert users. More user friendly software packages however do not
      normally incorporate the necessary flexibility for most research applications.
      This work presents a methodology based on Excel and Matlab-Simulink for both
      flexible and accessible implementation of mathematical models by researchers with
      and without programming expertise. The models are almost fully defined in an
      Excel file in which the names and values of the state variables and parameters
      are easily created. This information is automatically processed in Matlab to
      create the model structure and almost immediate model simulation, after only a
      minimum Matlab code definition, is possible. The framework proposed also provides
      programming expert researchers with a highly flexible and modifiable platform on
      which to base more complex model implementations. The method takes advantage of
      structural generalities in most mathematical models of environmental bioprocesses
      while enabling the integration of advanced elements (e.g. heuristic functions,
      correlations). The methodology has already been successfully used in a number of
      research studies.

PMID- 19182351
TI  - Coagulation-flocculation studies of tannery wastewater using cationic polymers as
      a replacement of metal salts.
AB  - Studies were conducted to evaluate the efficiency of cationic polymers as a
      suitable replacement of metal salts for the treatment of a local tannery
      wastewater. Eleven cationic polymers of varying molecular weights (MW) and charge
      densities (CD) were examined using jar test apparatus. Three cationic polymers:
      one with MW of 4 million Dalton and CD of 55%; second with MW of 6 million Dalton
      and CD of 40%; and the third with MW of 8 million Dalton and CD of 40% were found
      suitable for tannery wastewater treatment at an optimum dose of 20 mg/L for each.
      Percentage removals with these three cationic polymers for turbidity, total
      suspended solids (TSS), total chemical oxygen demand (TCOD) and chromium lied in
      a range of 91-95%, 69-83%, 25-29% and 96-97%, respectively with respect to plain
      settled wastewater. The cost of the most suitable cationic polymer C-496 at its
      optimum dose was $0.09 per cubic metre of wastewater and sludge production was 35
      mL/L. The results demonstrated that treatment of tannery wastewater with cationic
      polymers is a viable and economical option when compared with metal salts.

PMID- 19182352
TI  - Phosphorus retention patterns along the Tisza River, Hungary.
AB  - The aim of this study was to assess in-stream retention of suspended solids (SS)
      and total phosphorus (TP) at low flow condition in a large watercourse, the Tisza
      River. The analysis was based on a longitudinal water quality profile obtained in
      July 2006 during a cruise along the Hungarian section of the river (nearly 600
      km). Water samples were taken manually for SS and TP every half an hour (ca. 5.5
      km). Additionally, concentration of SS was calculated from on-line turbidity
      records taken every 6 s (ca. 10 m). Velocity field was calculated with a 1D
      hydrodynamic model calibrated for low flow conditions. To describe the transport,
      a simple first-order equation was adjusted to the SS profile after estimating the
      potential maximum of SS that the flow with the given velocity could transport.
      Specific P content of SS was related to velocity to estimate longitudinal TP
      profile. Retention of TP amounted to 42% along the Hungarian section of the Tisza
      River at a flow of 110 m(3) s(-1). Storage reservoirs significantly influenced
      the longitudinal retention pattern. Upstream of Dam II (river kilometre 404), net
      TP retention reached 73%, while the downstream section was a source of TP.

PMID- 19182353
TI  - [Management of phosphate in chronic kidney disease--Regulation of posphate
      homeostasis].
AB  - Inorganic phosphate (Pi) is an essential nutrient in terms of both cellular
      metabolism and skeletal mineralization. Dietary Pi is absorbed by the intestine,
      deposited in the bone and filtered by the kidney. Regulation of Pi
      absorption/reabsorption is achieved by changing the apical abundance of Na/Pi
      transporters (NaPi- II a, II b, and II c) . The regulatory mechanisms involve
      several signaling factors, such as parathyroid hormone (PTH) , 1,25 (OH)2D3, and
      fibroblast growth factor (FGF) -23. FGF-23, produced in the osteocytes, binds
      with FGF receptor (FGFR) and klotho in target organs (kidney or parathyroid grand
      et al.) and acts as a Pi regulating factor.

PMID- 19182354
TI  - [Disturbance of phosphorus metabolism in chronic kidney disease].
AB  - The kidney plays a central role in the maintenance of phosphorus homeostasis.
      Thus disturbance of phosphorus metabolism develops in most patients with chronic
      kidney disease (CKD) . Hyperphosphatemia typically occur in advanced CKD patients
      of whose glomerular filtration rate is <30 ml/min, whereas in early-stage CKD
      normophosphatemia is maintained by increased secretion of fibroblast growth
      factor-23 (FGF-23) and parathyroid hormone. Serum levels of these phosphaturic
      hormones increase along with the progression of CKD, leading to extremely high
      concentrations in dialysis patients, which in turn causes hypophosphatemia after
      kidney transplantation. Recently, besides phosphorus levels, increase in FGF-23
      levels has been shown to predict mortality and progression of CKD. Further
      studies should investigate whether management of phosphorus balance in early
      stage CKD is helpful in improving clinical outcomes and whether FGF-23 can be
      used as a potential biomarker for monitoring the response to its management.

PMID- 19182355
TI  - [Serum phosphate level and the prognosis of dialysis patients].
AB  - U-shaped relationship was observed between serum phosphate and mortality in
      dialysis patients. The connection between high serum phosphate and mortality can
      be explained partially by the contribution of phosphate to vascular calcification
      and oxidative stress in endothelial cells. Epidemiological study about the prior
      history of hip fracture in Japan revealed that high serum phosphate was
      associated with lower prevalence of prior fracture by univariate analysis.
      However, this association was eliminated by including many nutritional variables
      in multivariate analysis. This analysis also showed that severe hypophosphatemia
      less than 3 mg/dL was independently associated with high prevalence, implying the
      connection of malnutrition with bone health. Epidemiological data regarding
      incident fracture is also needed to know the factors really contributing to bone
      fragility. There is no way other than to determine target ranges of serum
      phosphate using observational studies, since interventional trial with hard
      outcome was practically impossible. The focus of observational studies will move
      on, in future, to the association between mortality and the methods to decrease
      serum phosphate level.

PMID- 19182356
TI  - [Roles of hyperphosphatemia in vascular calcification].
AB  - Derangemenst of mineral metabolism including hyperphosphatemia occur along with
      progression of chronic kidney disease (CKD) . Recent clinical studies suggest
      that hyperphosphatemia is a major risk factor for vascular calcification and
      cardiovascular mortality in dialysis patients. Two pathophysiological processes
      are involved in the development of vascular calcification : apoptosis and
      phenotypic transition to chondrocytes or osteoblasts (chondro-/osteogenic
      differentiation) . Inorganic phosphate has been demonstrated to induce apoptosis
      and calcification of vascular smooth muscle cells through inhibiting
      gas6/Axl/PI3K/Akt pathway (cell survival pathway) . Moreover, inorganic phosphate
      has been shown to promote in vitro calcification of vascular wall cells by
      stimulating osteoblastic differentiation through a type III sodium-dependent
      phosphate co-transporter (PiT-1) . These molecular mechanisms suggest that
      hyperphosphatemia may play a pivotal role in progression of vascular
      calcification in CKD.

PMID- 19182357
TI  - [Management of phosphate in nutrition therapy for chronic kidney disease].
AB  - Abnormality of serum phosphate levels, which is one of CKD-Mineral and Bone
      Disorder (CKD-MBD) , causes many complications such as cardiovascular disease and
      affects quality of life and prognosis. In CKD patients, phosphate uptake
      including food intake is one of the most important factor of phosphate control
      because ability of phosphate excretion is impaired. Concerning management of
      serum phosphate levels, regulation of protein intake, appropriate administration
      of phosphate binder, and prevention of constipation are essential.

PMID- 19182358
TI  - [Management of phosphate in chronic kidney disease--Phosphorus control by
      hemodialysis with long treatment time].
AB  - Hyperphosphatemia is an almost universal finding in patients with end-stage renal
      disease and is associated with increased all-cause mortality, cardiovascular
      mortality, and vascular calcification. Although new phosphate binders lead to a
      easy control of serum phosphorus levels, treatment time of a dialysis session
      might be the most important factor for controlling hyperphosphatemia. Two
      alternatives to conventional thrice weekly dialysis (CHD) are nocturnal
      hemodialysis (NHD) and short daily hemodialysis (SDHD) . The total weekly
      phosphorus removal with NHD and SDHS is significantly greater than that removed
      by CHD and this is associated with a significantly lower average serum
      phosphorous.

PMID- 19182359
TI  - [Management of phosphate in chronic kidney disease--Chemistry and history of
      phosphate binder].
AB  - In 1960s and 1970s when hemodialysis therapy was started in Japan, calcium
      carbonate was used as a phosphate binder and as the purpose of calcium
      supplement. Aluminum preparations were widely used in Japan, Europe and United
      states since the end of 1970s, when these drugs were reported as a strong
      phosphate binder. After that, some adverse effects such as encephalopathy and
      bone lesions attributed to Aluminum administration have become serious problems
      in dialysis patients. As a result, Aluminum administration was prohibited in 1992
      in Japan. Oral vitamin D pulse therapy was developed in 1990s as a treatment for
      secondary hyperparathyroidism in Japan, hypercalcemia have been occurred easily
      by combination use of vitamin D preparations and calcium carbonate. Since the
      2000s, various complications, such as ectopic calcifications, cardiovascular
      diseases, and reduced life expectancy, which are associated with hypercalcemia
      and hyperphosphatemia have been clarified. Therefore, sevelamer hydrochrolide,
      that is non calcium phosphate binder, became available from 2003. Moreover,
      Lanthanum carbonate, that is another type of non calcium phosphate binder, was
      effective in Europe and United States, and also developing in Japan. However,
      there are not any phosphate binders which solved all clinical problems such as
      phosphate adsorptive power, digestive symptoms, and organ accumulation.

PMID- 19182360
TI  - [Management of hyperphosphatemia ; phosphate-binder].
AB  - Numerous experimental and clinical studies have recently addressed the underlying
      mechanisms in particular the marked increase in cardiovascular mortality in
      patients with CKD. Hyperphosphatemia is a major problem in these patients with
      advanced stage of CKD. Calcium carbonate became the most widely used phosphate
      binders ; however, increasing evidence now suggests that prolonged use of these
      agents increases the total body calcium load, induces adynamic bone, and
      potentially increases the risk of cardiovascular and soft tissue calcification.
      Sevelamer is the first phosphate-binding agent that is non-absorbed, calcium
      free, and metal-free. To date, this agent has been shown to effectively control
      serum phosphorus levels in patients with CKD. It may also attenuate coronary and
      aortic calcification and has a number of other beneficial effects on lipid
      metabolism and inflammation among others.

PMID- 19182361
TI  - [Pharmacodynamic and pharmacokinetic profile of lanthanum carbonate].
AB  - Lanthanum (La) is a rare-earth element in transition Group III b of the periodic
      table. It is a ductile and malleable, silvery-white metal, soft enough to be cut
      with a knife. Lanthanum carbonate (La2[CO3]3) is the most recent non-calcium, non
      aluminum phosphate binder to be developed for the treatment of hyperphosphatemia.
      This drug has already been registered and available in the US and EU.
      Precilinical studies have shown that it is as effective as aluminium, without the
      associated toxicity, and is minimally absorbed. In clinical studies (La2[CO3]3)
      has a similar ability to calcium carbonate in controlling serum phosphate level
      without hypercalcemia. In this review I would like to summarize the
      pharmacodynamic and pharmacokinetic profile of this new phosphate binder
      (La2[CO3]3) which will be registered in our country in the near future.

PMID- 19182362
TI  - [Management of phosphate in chronic kidney disease--Clinical trials of lanthanum
      carbonate].
AB  - The lanthanum carbonate which is the new phosphate binder decreased serum
      phosphorus value significantly in comparison with the placebo group, showed equal
      serum phosphorus decrease action to those at the capacity which in addition is
      less than calcium carbonate and sevelamer hydrochloride.

PMID- 19182363
TI  - [Is lanthanum carbonate a safe drug?].
AB  - Lanthanum carbonate is drawing attention as a new effective oral phosphate
      binder. This drug shares a character that "heavy metal that is not the natural
      constituent of human body and ionizes into free cations in gastrointestinal
      tract" with aluminum hydroxide gel. In fact, although the amount is much less
      than that of aluminum hydroxide gel, lanthanum is absorbed through intestine and
      accumulated in the body. Fortunately, there has been no report about the toxicity
      of such accumulated lanthanum. However, it does never mean that "lanthanum
      carbonate is harmless", since it usually takes years to demonstrate metal
      toxicity.

PMID- 19182364
TI  - [Use of phosphate binder in predialysis patients].
AB  - Recently, it is evident that sevelamer hydrochloride is superior to calcium
      carbonate in the anti-phosphorus therapy for the dialysis patients, from the
      viewpoints of vascular calcification and mortality. The efficacy of sevelamer
      hydrochloride was also suggested in predialysis patients. Although, in Japan,
      calcium carbonate, but not sevelamer, is only approved to the treatment in
      predialysis patients. It should be discussed about lanthanum carbonate. In this
      review, the management of phosphorus and the administration of phosphate binder
      in predialysis patients are extrapolated.

PMID- 19182365
TI  - [Novel phosphate binders under development].
AB  - Controlling serum phosphorus levels in patients with chronic kidney disease is
      crucial. Since hyperphosphatemia is an established risk factor for not only
      secondary hyperparathyroidism, but also cardiovascular mortality in these
      patients, the adequate control of serum phosphorus is necessary. The target
      levels of serum phosphorus, however, are not consistently being met. To achieve
      better control of serum phosphorus levels, some novel phosphate binders, which do
      not contain calcium or metal, have been developed. In this manuscript we discuss
      some novel phosphate binders, which are now in clinical trials.

PMID- 19182366
TI  - [Progress in the identification of intestinal Pi transport inhibitors].
AB  - In 2003, the NKF K/DOQI released new clinical practice guidelines for bone
      metabolism and disease in chronic kidney disease, respectively. Target level of
      phosphate and Ca x Pi products are set at relative low levels in the new
      guidelines. Prescription of a new phosphate binder, severamer hydrochloride, a
      widely recommended in this quideline. Other approaches that could prove fruitful
      include inhibition of intestinal and renal phosphate transporters. Inhibition of
      the sodium-dependent phosphate transporter by a small molecule would be a
      desirable method to control serum phosphate levels in patients with chronic renal
      disease or undergoning dialysis. In this review the progress in the
      identification of such an agent is discussed.

PMID- 19182367
TI  - [To facilitate the compliance of phosphate binder for the control of
      hyperphosphatemia in chronic kidney disease patients].
AB  - Despite phosphate binders are necessary for the control of hyperphosphatemia in
      chronic kidney disease, adherence to medication tends to be low due to the lack
      of subjective symptoms of patients. Such non- adherence often causes compromised
      health outcomes. Key factors affecting adherence of phosphate binders are being
      the occurrence of side effects such as constipation, taking a lot of tablets,
      being lack of motive for medication. Thus, to facilitate the adherence of
      phosphate binders, it is recommended to select medication properly according to
      the situation of individual patients, to consider the side effect reduction and
      to raise motive of adherence by educational interventions and drug counseling.

PMID- 19182368
TI  - [Bisphosphonates and other new therapeutic agents for the treatmednt of
      osteogenesis imperfecta].
AB  - Osteogenesis imperfecta (OI) is a genetic disorder characterized by fragile bone
      and reduced bone mineral density. Cyclic intravenous pamidronate is now the
      standard treatment for moderate to severe forms of OI, however clinical studies
      are not yet sufficient to conclude appropriate annual doze and ideal duration of
      therapy at present time. Oral alendronate is also effective in milder forms of
      OI. Zoledronic acid has undergone international multicentric clinical trials to
      examine efficiency and long-term side effects including osteonecrosis of the jaw.
      Teriparatide (rhPTH1-34) and denosumab (monoclonal antibody against RANK ligand)
      have the potential for management of OI. Stem cell and gene therapy are currently
      being actively investigated and may become clinically applicable in the near
      future.

PMID- 19182369
TI  - The role of calreticulin transacetylase in the activation of human platelet
      nitrite reductase by polyphenolic acetates.
AB  - Our earlier investigations demonstrated the remarkable activation of cytochrome P
      450 reductase and nitric oxide synthase by 7,8-diacetoxy-4-methylcoumarin, a
      model polyphenolic acetate by way of acetylation, catalyzed by the Calreticulin.
      Protein acetyltransferase action of Calreticulin was hence termed Calreticulin
      transacetylase (CRTAase). Nitric oxide synthase and nitrite reductase are now
      considered as parts of nitric oxide cycle. The activation of platelets nitric
      oxide synthase by 7,8-diacetoxy-4-methylcoumarin has already been demonstrated by
      us. Also, there are reports that certain proteins such as cytochrome P-450
      reductase and cytochrome P-450 are endowed with the nitrite reductase activity in
      mammalian cells. Keeping these facts in view, we turned our attention to probe
      whether 7,8-diacetoxy-4-methylcoumarin could alter the levels of nitric oxide
      independent of the action of nitric oxide synthase in the human platelets model.
      The incubation of 7,8-diacetoxy-4-methylcoumarin and nitrite with platelets
      caused significant elevation of nitric oxide and cyclic guanosine monophosphate
      levels possibly due to the activation of nitrite reductase. Several polyphenolic
      acetates were similarly found to activate the nitrite reductase in tune with
      their affinities as substrate to CRTAase. N-omega-Nitro-L-arginine methyl ester,
      the inhibitor of nitric oxide synthase, failed to reverse such an effect of 7,8
      diacetoxy-4-methylcoumarin. Clotrimazole which is known to be an inhibitor of
      nitrite reductase, effectively abolished the 7,8-diacetoxy-4-methylcoumarin
      mediated enhancement of nitric oxide levels in platelets as well as the nitric
      oxide mediated effects; such as cyclic guanosine monophosphate levels as well as
      adenosine diphospate induced platelets aggregation due to nitrite.

PMID- 19182370
TI  - Preventive effect of 7,8-dihydroxyflavone against oxidative stress induced
      genotoxicity.
AB  - We elucidated the protective effect of 7,8-dihydroxyflavone against hydrogen
      peroxide (H(2)O(2))-induced DNA damage. We found that 7,8-dihydroxyflavone
      scavenges 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and intracellular reactive
      oxygen species (ROS). 7,8-Dihydroxyflavone with antioxidant effect prevented the
      H(2)O(2)-induced cellular DNA damage, as evidenced by comet tail, 8-hydroxy-2'
      deoxyguanosine (8-OHdG) content, and phospho-histone H2A.X protein expression.
      Hence, 7,8-dihydroxyflavone was shown to protect cell via the inhibition of
      apoptosis induced by H(2)O(2). This was substantiated by decreased apoptotic
      nuclear fragmentation, decreased sub-G(1) cell population, and decreased DNA
      fragmentation. Furthermore, 7,8-dihydroxyflavone activated the protein kinase B
      (PKB, Akt) signal pathway, which is a major survival signal pathway. In addition,
      LY294002, which is phosphatidylinositol 3 kinase (PI3K, upstream of Akt)
      inhibitor, attenuated the protective effect of 7,8-dihydroxyflavone against
      H(2)O(2)-induced cell damage. In conclusion, 7,8-dihydroxyflavone was shown to
      possess cytoprotective properties against oxidative stress by scavenging
      intracellular ROS and enhancing Akt activity.

PMID- 19182372
TI  - Thrombomodulin suppresses invasiveness of HT1080 tumor cells by reducing
      plasminogen activation on the cell surface through activation of thrombin
      activatable fibrinolysis inhibitor.
AB  - Cell malignancy is negatively correlated with the expression of thrombomodulin
      (TM), a thrombin receptor expressed on the surface of various cells, including
      tumor cells. TM accelerates thrombin-activatable fibrinolysis inhibitor (TAFI)
      activation catalyzed by thrombin. The active form of TAFI (TAFIa) contributes to
      inhibition of plasmin formation through its carboxypeptidase B (CPB)-like
      activity. Here, we examined whether TM- and tumor cell-dependent TAFI activation
      participates in controlling pericellular fibrinolysis and cell invasion. Human
      fibrosarcoma HT1080 cells retained the ability to activate both prothrombin and
      plasminogen, but did not express TM. HT1080 cells mediated activation of TAFI in
      plasma in the presence of soluble-type TM (sTM) through cell-dependent
      prothrombin activation. HT1080 cells stably expressing TM (TM-HT1080) mediated
      plasma TAFI activation without added sTM, but HT1080 (wild-type) and Mock
      transfected HT1080 cells (Mock) did not. Production of TAFIa suppressed cell
      mediated plasminogen activation. Matrigel invasion by wild-type and Mock cells
      was enhanced two-fold by diluted plasma (10%), whereas the plasma-induced
      invasion of TM-HT1080 cells (65% of wild-type invasion) was lower than those of
      wild-type and Mock cells. Cell invasion by TM-HT1080 was partially enhanced by
      addition of a TAFIa/CPB inhibitor. These results suggest that TM suppresses
      pericellular fibrinolysis and plasma-induced tumor cell invasion, and that it is
      mediated, at least in part, by plasma TAFI activation.

PMID- 19182371
TI  - Bile acid-induced elevated oxidative stress in the absence of farnesoid X
      receptor.
AB  - The major function of farnesoid X receptor (FXR) is to maintain bile acid and
      lipid homeostasis. Fxr-null mice, in which the levels of hepatic bile acid and
      lipid have been elevated, develop spontaneous liver tumors. We evaluated
      differences in hepatic bile acid and triglyceride concentrations, and in
      generation of oxidative stress between wild-type mice and Fxr-null mice. The
      hepatic levels of 8-hydroxy-2'-deoxyguanosine (8OHdG), thiobarbituric acid
      reactive substance (TBARS) and hydroperoxides, oxidative stress-related genes,
      and nuclear factor (erythroid-2 like) factor 2 (Nrf2) protein in Fxr-null mice
      were significantly higher than those in wild-type mice. An increase in the
      hepatic bile acid concentration in Fxr-null mice fed a cholic acid (CA) diet
      resulted in an increase in the hepatic levels of hydroperoxides, TBARS and 8OHdG,
      whereas a decrease in the hepatic concentration in mice fed a diet containing
      ME3738 (22beta-methoxyolean-12-ene-3beta,24(4beta)-diol) resulted in a decrease
      in these oxidative stress marker levels. A good correlation was observed between
      the hepatic bile acid concentrations and the hepatic oxidative stress marker
      levels, although there was no significant correlation between the hepatic
      triglyceride concentrations and oxidative stress. The results show that oxidative
      stress is spontaneously enhanced in Fxr-null mice, which may be attributable to a
      continuously high level of hepatic bile acids.

PMID- 19182373
TI  - Oxidative stress induced by a dihydropyrazine derivative.
AB  - The Maillard reaction contributes to the complications of diabetes and normal
      aging. Dihydropyrazines (DHPs), which are produced during the Maillard reaction,
      generate radicals and possess DNA strand-cleaving activities in vitro. In the
      present study, we evaluated the genotoxic and cytotoxic potentials of a DHP
      derivative, cyclohexyl-DHP, which is obtained as a mixture of two isomers,
      2,3,5,6,7,8-hexahydroquinoxaline (endo-type) and 1,2,3,5,6,7-hexahydroquinoxaline
      (exo-type), fused with a cyclohexyl ring. Cyclohexyl-DHP caused DNA strand breaks
      in plasmid pUC18, especially in the presence of Cu(2+). By using Escherichia coli
      mutant strains, we observed that cyclohexyl-DHP exposure strongly reduced the
      survival rate of a cytosolic sodium dodecyl sulfate (SOD)-deficient strain (sodA
      sodB), significantly reduced the survival rates of DNA repair-deficient strains
      (recA and uvrB) and mildly reduced the survival rate of a catalase-deficient
      strain (katE katG) compared with the survival rate of the wild-type strain.
      Addition of Cu(2+) enhanced the cell killing ability of cyclohexyl-DHP. The
      frequency of mutations induced by cyclohexyl-DHP increased dose-dependently in
      the sodA sodB strain. Assays with the highly water-soluble tetrazolium salt WST-1
      revealed that cyclohexyl-DHP strongly generated superoxide anions. Moreover,
      cyclohexyl-DHP elevated the protein carbonyl levels in E. coli. These findings
      indicate that cyclohexyl-DHP could potentially generate superoxide anions, and
      cause not only breakage of chromosomal DNA leading to mutagenic lesions but also
      induce damage to cellular proteins.

PMID- 19182374
TI  - Effects of selenium deficiency on aldehyde oxidase 1 in rats.
AB  - Selenium deficiency has been reported to result in an extraordinary decrease of
      glutathione peroxidase (GSH-Px) and, reversely, an increase of detoxifying
      enzymes such as glutathione-S-transferase (GST), uridine-5'-diphosphate
      glucuronosyltransferase (UGT), nicotinamide-dependent quinine oxidoreductase
      (NQO1; DT-diaphorase), and epoxide hydrolase without significantly affecting
      cytochrome P450 activity. However, little is known about the effects on aldehyde
      oxidase 1 (AOX1) activity towards various kinds of aldehydes and N-heterocyclic
      aromatic compounds. The aim of this study is to clarify the effects of selenium
      deficiency on AOX1 in rats. As expected, selenium deficiency was confirmed by the
      extremely low activity of GSH-Px along with the increased activities of GST and
      DT-diaphorase. AOX1 activity towards vanillin and (S)-RS-8359 was increased by
      selenium deficiency, and that corresponded to an increase of AOX1 protein level
      but not to a decreased AOX1 mRNA level. It has been documented that the assembly
      of the catalytically active holoenzyme forms of the molybdo-flavoenzyme family is
      very complex and is controlled through transcriptional and translational events
      by many gene products. In addition, selenium deficiency has been known to cause
      oxidative stress that leads to an increase of AOX1 activity. Furthermore,
      aldehyde oxidase homolog 1 (AOH1) with properties similar to AOX1 is present in
      rodent liver. All the reports suggest that the mechanisms by which selenium
      deficiency increases AOX1 activity are highly complicated and investigated from
      different points of view.

PMID- 19182375
TI  - Comparative study on the nuclear hormone receptor activity of various
      phytochemicals and their metabolites by reporter gene assays using Chinese
      hamster ovary cells.
AB  - Phytochemicals are naturally present in a wide variety of plants, and have been
      suggested to exert a number of effects beneficial to human health. Several
      phytochemicals possess estrogenic activity through estrogen receptor alpha
      (ERalpha) and ERbeta, and are, therefore, termed phytoestrogens. In this study,
      we examined whether various phytochemicals have agonistic and/or antagonistic
      activity against six human nuclear receptors (ERalpha, ERbeta, androgen receptor
      (AR), glucocorticoid receptor (GR), thyroid hormone receptor alpha(1)
      (TRalpha(1)) and TRbeta(1)) by in vitro reporter gene assays using Chinese
      hamster ovary cells. Of the 31 phytochemicals tested, including flavonoids,
      isoflavonoids, coumestan, lignans, catechins and their metabolites, 20 compounds
      showed estrogenic activity via ERalpha and/or ERbeta, and we ranked these
      phytochemicals according to their estrogenic potency via ERalpha and ERbeta. As a
      result, coumestrol and genistein strongly activated ERalpha and ERbeta at very
      low concentrations of <1x10(-10) M. Most phytochemicals showing estrogenic
      activity also exhibited agonistic activity against ERbeta at lower concentrations
      than those for ERalpha, and two typical isoflavones, genistein and daidzein, in
      particular, showed a potent preference for ERbeta. Further, we found that
      baicalein has ERbeta antagonistic activity, and two compounds, enterolacton and O
      desmethylangolensin, have AR antagonistic activity. Nevertheless, none of tested
      compounds showed AR agonistic activity together with GR, TRalpha(1) and TRbeta(1)
      agonistic/antagonistic activity. These results suggest that various
      phytochemicals or their metabolites preferentially interact with ERalpha/beta
      among the six nuclear hormone receptors tested, and that the ERbeta agonistic
      activity, in particular, of these compounds may be associated with various
      beneficial effects on human health.

PMID- 19182376
TI  - Evaluation of the skin irritation using a DNA microarray on a reconstructed human
      epidermal model.
AB  - To avoid the need to use animals to test the skin irritancy potential of
      chemicals and cosmetics, it is important to establish an in vitro method based on
      the reconstructed human epidermal model. To evaluate skin irritancy efficiently
      and sensitively, we determined the gene expression induced by a topically-applied
      mild irritant sodium dodecyl sulfate (SDS) in a reconstructed human epidermal
      model LabCyte EPI-MODEL (LabCyte) using a DNA microarray carrying genes that were
      related to inflammation, immunity, stress and housekeeping. The expression and
      secretion of IL-1alpha in reconstructed human epidermal culture is known to be
      induced by irritation. We detected the induction of IL-1alpha expression and its
      secretion into the cell culture medium by treatment with 0.075% SDS for 18 h in
      LabCyte culture using DNA microarray, quantitative reverse-transcription
      polymerase chain reaction (RT-PCR) and ELISA. DNA microarray analysis indicated
      that the expression of 10 of the 205 genes carried on the DNA microarray was
      significantly induced in a LabCyte culture by 0.05% or 0.075% SDS irritation for
      18 h. RT-PCR analysis confirmed that SDS treatment significantly induced the
      expressions of interleukin-1 receptor antagonist (IL-1RN), FOS-like antigen 1
      (FOSL1), heat shock 70 kDa protein 1A (HSPA1) and myeloid differentiation primary
      response gene (88) (MYD88), as well as the known marker genes for irritation IL
      1beta and IL-8 in a LabCyte culture. Our results showed that a DNA microarray is
      a useful tool for efficiently evaluating mild skin irritation using a
      reconstructed human epidermal model.

PMID- 19182377
TI  - Role of dexamethasone and oncostatin M on the formation of vacuoles in human
      fetal liver cells.
AB  - Combined treatment with dexamethasone and oncostatin M (DEX/OSM) or interleukin-6
      (DEX/IL-6) resulted in the appearance of numerous large vacuoles in human fetal
      liver (HFL) cells and showed synergistic effects on the formation of vacuoles.
      The number of vacuoles formed by DEX, DEX/OSM, or DEX/IL-6 was significantly
      suppressed by RU-486, a glucocorticoid receptor antagonist. On the other hand,
      the size of vacuoles formed by OSM, IL-6, DEX/OSM, or DEX/IL-6 was significantly
      decreased to about 65% by madindoline A (MDL-A), which is a non-peptide
      antagonist of gp130 and an inhibitor of cytokines, such as IL-6, mediated by
      gp130 homodimerization, while RU-486 did not affect the size of vacuoles.
      Expression of IL-6 mRNA in HFL cells was markedly induced by OSM. Expression of
      IL-6R mRNA was induced by DEX. These results indicate that DEX contributes to the
      formation of vacuoles through glucocorticoid receptors and that OSM and IL-6
      contribute to enlargement of these vacuoles.

PMID- 19182378
TI  - Hwanggunchungyitang prevents cadmium-induced ototoxicity through suppression of
      the activation of caspase-9 and extracellular signal-related kinase in auditory
      HEI-OC1 cells.
AB  - Hwanggunchungyitang (HGCYT) is a newly designed herbal drug formula for the
      purpose of treating auditory diseases. A number of heavy metals have been
      associated with toxic effects to the peripheral or central auditory system.
      Cadmium (Cd(2+)) is a heavy metal and a potent carcinogen implicated in tumor
      development through occupational and environmental exposure. However, the
      auditory effect of Cd(2+) is not poorly understood. The purpose of the present
      study was to investigate whether HGCYT prevent the ototoxic effects induced by
      Cd(2+) in auditory cell line, HEI-OC1. HGCYT inhibited the cell death, reactive
      oxygen species generation (ROS), activation of caspase-9, and extracellular
      signal-related kinase (ERK) induced by Cd(2+). In addition, we observed that
      cochlear hair cells in middle turn were damaged by Cd(2+). However, HGCYT
      prevented the destruction of hair cell arrays of the rat primary organ of Corti
      explants in the presence of Cd(2+). These results support the notion that ROS are
      involved in Cd(2+) ototoxicity and suggest HGCYT therapeutic usefulness, against
      Cd(2+)-induced activation of caspase-9 and ERK.

PMID- 19182379
TI  - Protective effect of Tanshinone IIA on the early stage of experimental diabetic
      nephropathy.
AB  - Diabetic nephropathy (DN) has become the leading cause of end stage renal
      failure, and prevention or retardation of DN has become a major goal in
      biomedical research. In this study, Tanshinone IIA, a component extracted from
      Salvia miltiorrhiza, was studied in experimental rats in which DN was induced by
      streptozotocin (STZ) treatment. The DN rats were treated with 10 mg/kg of
      Tanshinone IIA for 12 weeks to analyze its reno-protective effect with different
      parameters. Renal hypertrophy and 24-h urinary protein excretion were ameliorated
      by Tanshinone IIA. Moreover, advanced glycation end-products (AGEs), angiotensin
      II (Ang II), transforming growth factor beta(1) (TGF-beta(1)), collagen IV, and
      monocyte/macrophage (ED-1) either in the serum or kidney were significantly
      reduced. These results suggest that Tanshinone IIA might have protective effects
      on several pharmacological targets during the progression of DN, and could be a
      potential drug for the prevention of DN.

PMID- 19182380
TI  - The effect of Am-80, a synthetic retinoid, on spinal cord injury-induced motor
      dysfunction in rats.
AB  - The present study investigated the effect of 4[(5,6,7,8-tetrahydro-5,5,8,8,
      tetramethyl-2-naphthalenyl)carbamoyl] benzoic acid (Am-80), a synthetic retinoid,
      on spinal cord injury (SCI) in rats. Treatment with Am-80 (orally and
      subcutaneously) significantly promoted recovery from SCI-induced motor
      dysfunction. On day 28 after injury, the lesion cavity was markedly reduced,
      while the expression of myelin basic protein (MBP; myelin), betaIIItubulin
      (neuron), and glial fibrillary acidic protein (GFAP; astrocyte) was increased, in
      comparison with SCI controls. Interestingly, expression of neurotrophin receptor,
      tyrosine kinase B (TrkB) was over 3-fold higher after Am-80 treatment than in SCI
      controls. A lot of TrkB-positive cells as well as brain-derived neurotrophic
      factor (BDNF)-positive ones were observed around the injured site. Am-80 (10
      microM) combined with BDNF (100 ng/ml) promoted extensive neurite outgrowth and
      TrkB gene expression by cultured SH-SY5Y cells, as did all-trans retinoic acid
      (ATRA). Thymidine incorporation was dramatically suppressed, but there was little
      effect on cell viability. These findings suggest that Am-80 has the potential to
      be used for treating neurodegenerative disorders, including SCI. Its efficacy may
      be partly ascribed to promotion of cell viability and differentiation of neural
      stem cells through increased TrkB expression.

PMID- 19182381
TI  - Oral glutamine dipeptide prevents against prolonged hypoglycemia induced by
      Detemir insulin in rats.
AB  - The role of glutamine dipeptide (GDP) to prevent against prolonged insulin
      induced hypoglycemia (IIH) in overnight fasted rats was investigated. The
      glycemia was measured 0, 2, 4, 8, and 10 h after an intraperitoneal (i.p.)
      injection (1 U/kg) of Detemir insulin. Because the lowest glycemia was obtained 4
      h after insulin administration, the experiments were done at this time. The
      hypoglycemia obtained 4 h after insulin injection was partially prevented with
      increasing oral doses of GDP (1.56, 3.12, 6.25, 12.5 mg/kg). The best result was
      obtained with 12.5 mg/kg. However, from this dose (25.0, 50.0, 100.0 mg/kg), the
      values of glycemia progressively decreased (p<0.05). The effect of GDP to prevent
      prolonged IIH was mediated, partly at least, by an intensification of liver
      gluconeogenesis. Moreover, the increased portal availability of GDP, L-alanine
      and L-glutamine after GDP administration also contributed to the IIH prevention,
      since the rate of gluconeogenesis progressively augmented with the infusion of
      increasing concentrations of these substances. However, after getting the maximal
      value, the rate of liver gluconeogenesis decreased (p<0.05) if a more elevated
      concentration of L-alanine or L-glutamine was infused. On the other hand, the
      liver gluconeogenesis during the infusion of increasing concentrations of GDP was
      unchanged. Because, GDP did not directly inhibit liver gluconeogenesis, but an
      inhibition of this metabolic pathway was observed with low ammonia concentrations
      (from 0.062 mM) it is possible that the ammonia from the catabolism of GDP by
      extra hepatic tissues could inhibit liver gluconeogenesis. This mechanism could
      help to explain the lower glycemia obtained with more elevated doses of oral GDP.

PMID- 19182382
TI  - Goshuyuto, a traditional Japanese medicine, and aqueous extracts of Evodiae
      Fructus constrict isolated rat aorta via adrenergic and/or serotonergic
      receptors.
AB  - Effects of goshuyuto, a traditional Japanese medicine, on vascular constriction
      were examined using isolated strips of rat aorta. Goshuyuto (1 x 10(-5) to 1 x
      10(-3) g/ml) caused constriction of aorta strips in a dose-dependent manner. The
      vasoconstrictive effects of goshuyuto were significantly inhibited by
      pretreatment with prazosin, an adrenergic alpha(1) receptor antagonist. The
      constrictive effects were partially inhibited by pretreatment with BRL15572, a 5
      HT(1D) antagonist, and ketanserin, a 5-HT(2A) antagonist. However, the
      constrictive effects were not inhibited by pretreatment with SB216641, a 5-HT(1B)
      antagonist, or propranolol, an adrenergic beta receptor antagonist. In addition,
      aqueous extracts of Evodiae Fructus, one of the constituent medicinal herbs of
      goshuyuto, caused constriction of aorta strips strongly, but aqueous extracts of
      Zizyphi Fructus, Ginseng Radix, and Zingiberis Rhizoma, the other constituents of
      goshuyuto, did not have much effect on the vascular response of rat aorta strips.
      Also, synephrine, which is one of the ingredients of Evodiae Fructus, constricted
      the rat aorta. These results suggest that goshuyuto constricts rat aorta strips
      and that the mechanisms involve the adrenergic and/or serotonergic receptors.
      Also, it may be suggested that Evodiae Fructus and synephrine play the important
      role in the vasoconstrictive effects of goshuyuto on rat aorta strips.

PMID- 19182383
TI  - Mangiferin ameliorates scopolamine-induced learning deficits in mice.
AB  - The aim of this study was to evaluate the effects of Anemarrhena asphodeloides
      BUNGE (AA) on cholinergic memory deficits in mice. This agent has previously been
      used as an antipyretic, anti-inflammatory, anti-diabetic, and antidepressant in
      traditional Chinese medicine. Mangiferin was isolated from AA and showed a dose
      dependent inhibition of acetylcholinesterase (AChE) activity (IC(50) value, 62.8
      microM). Cholinergic dysfunction was induced in mice by administering
      scopolamine, and the animals were then tested using the passive avoidance test as
      well as the Morris water maze test. Mangiferin (20 mg/kg, p.o.) significantly
      reversed scopolamine-induced deficits in the passive avoidance test, and also
      improved escape latencies in training trials and increased swimming times in the
      Morris water maze test (p<0.05). Mangiferin also reduced acetylcholine and tumor
      necrosis factor (TNF)-alpha levels induced by scopolamine in mice brain (p<0.05)
      and inhibited nuclear factor (NF)-kappaB activation in scopolamine or TNF-alpha
      stimulated BV-2 microglial cells. These results suggest that mangiferin can
      improve long-term cholinergic memory deficits by AChE inhibition or cholinergic
      receptor stimulation and inhibition of NF-kappaB activation.

PMID- 19182384
TI  - The anti-stress effects of Sarcandra glabra extract on restraint-evoked
      immunocompromise.
AB  - Sarcandra glabra was a renowned herb traditionally used as herbal tea or food
      supplement to enhance mental efficiency and to recover from stress or fatigue in
      China. We investigated the effects of Sarcandra glabra extract (SGE), with
      chemical composition clearly showed by HPLC fingerprint as quality control, on
      immunologic response including natural killer (NK) cell activity and its
      antioxidative capacity in splenocytes obtained from restraint mice. Our results
      found that daily oral administration of SGE (125, 500 mg/kg/d) for 5 consecutive
      days to restrained mice alleviated the stress-induced reduction of the number of
      lymphocytes, the balance of CD4(+) T/CD8(+) T and NK cell activity per spleen.
      SGE also significantly decreased the level of lipid peroxidation and increased
      oxygen radical absorbance capacity (ORAC) in splenocytes. These results indicated
      that SGE modulate stress-attenuated immunologic response, at least, partially
      explained by improving antioxidative capacity in immunocytes.

PMID- 19182385
TI  - Inhibition of coagulation activation and inflammation by a novel Factor Xa
      inhibitor synthesized from the earthworm Eisenia andrei.
AB  - We have cloned an earthworm-derived Factor Xa (FXa) inhibitor, with an excellent
      inhibitory specificity from the midgut of the Eisenia andrei. We designate this
      inhibitor eisenstasin. An eisenstasin-derived small peptide (ESP) was synthesized
      and we examined whether ESP played an essential role in FXa inhibition. Compared
      to antistasin-derived small peptides (ASP) originating from leech, ESP primarily
      exhibited a high level of FXa inhibition in chromogenic peptide substrate assays
      and revealed an approximately 2-fold greater inhibition of FXa cleavage of a
      target protein than ASP. This suggests that ESP could be an effective anti
      coagulant that targets FXa during the propagation step of coagulation. ESP also
      inhibited proteinase-activated receptor 2-mediated FXa activation, which may
      trigger endothelial inflammation. Endothelial nitric oxide (NO) was significantly
      reduced by ESP (p<0.0001), indicating that protease-activated receptor-2 (PAR-2)
      was effectively inactivated. We also found that ESP reduced the expressions of
      pro-inflammatory cytokines (IL-1alpha, IL-1beta, IL-8, IL-16, MCP-1, MIP-1alpha
      and MIP-1beta) by cultured cells treated with both ESP and FXa. Our results
      provide the first evidence that ESP might interrupt coagulation cascades by
      inhibiting FXa, and thereby may effectively control the bidirectional alternation
      between coagulation and inflammation.

PMID- 19182386
TI  - Anti-angiogenic and anti-metastatic effects of beta-1,3-D-glucan purified from
      Hanabiratake, Sparassis crispa.
AB  - Sparassis crispa (SC), Hanabiratake in Japanese, is an edible mushroom with
      medicinal properties, that contains more than 40% beta-D-glucan. It was concluded
      from results of the methylation study that beta-D-glucan from SC (SBG) was
      composed of a backbone of beta-(1-->3)-linked D-glucopyranosyl residues, and had
      beta-D-glucopyranosyl groups joined through O-6 and O-2 of D-glucose of the
      backbone. We purified SBG and investigated its anti-angiogenic functions and anti
      metastatic effects on neoplasm using different animal models. The oral
      administration of the purified SBG suppressed B16-F10 cell-induced angiogenesis
      in the dorsal air sac assay using female ICR mice as well as vascular endothelial
      growth factor induced neovascularization in the Matrigel plug assay using female
      C57BL/6J mice. Furthermore, it suppressed the growth and numbers of the
      metastatic tumor foci in lung, along with the primary tumor growth in the
      spontaneous metastatic model using female C57BL/6J mice. From these results, it
      is apparent that the oral administration of SBG results in suppressive effect on
      tumor growth and metastasis in lung through the inhibition of tumor induced
      angiogenesis. These effects are not a result of direct action on the endothelial
      cells because cell growth, migration and capillary-like tube formation were not
      affected in the human umbilical vein endothelial cells by SBG application. This
      is the first report showing that the oral administration of SBG is capable of
      suppressing angiogenesis and metastasis.

PMID- 19182387
TI  - Inhibitory effects of calycosin isolated from the root of Astragalus membranaceus
      on melanin biosynthesis.
AB  - Tyrosinase is a key enzyme for melanin biosynthesis, and hyperpigmentation
      disorders are associated with abnormal accumulation of melanin pigments, which
      can be reduced by treatment with depigmenting agents. A methanol extract of
      Astragalus membranaceus showed inhibitory activity against mushroom tyrosinase.
      The active compound was purified from the methanol extract of A. membranaceus
      and, following several chromatographic methods, was identified as calycosin via
      spectroscopic analysis. The results showed that calycosin exhibited tyrosinase
      inhibitory activity with an IC(50) value of 38.4 microM. Moreover, calycosin
      showed a melanin biosynthesis inhibition zone in a culture plate of Streptomyces
      bikiniensis, which is commonly used as an indicator organism. Furthermore,
      calycosin dramatically reduced melanin synthesis of Melan-a cells without any
      apparent cytotoxicity and reduced expression of melanogenic enzyme, tyrosinase.
      These results suggest that calycosin may be an effective skin-lightening agent
      that regulates the expression of melanogenic enzymes.

PMID- 19182389
TI  - Sustained-release progesterone vaginal suppositories 1--development of sustained
      release granule--.
AB  - Progesterone (P) is an important hormone for the establishment of pregnancy, and
      its administration is useful for luteal insufficiency. Considering the problems
      of commercially available oral and injection drugs, hospital-formulated vaginal
      suppositories are clinically used. However, since the half-life of P
      suppositories is short, it is difficult to maintain its constant blood
      concentration. To sustain drug efficacy and prevent side-effects, we are
      attempting to develop sustained-release suppositories by examining the degree of
      sustained-release of active ingredients. In this study, we examined the
      combinations of granulation methods and release systems for the preparation of
      sustained-release granules of P, and produced 13 types of sustained-release
      granules. We also examined the diameter, content, and dissolution of each type of
      granules, and confirmed that the sustained-release of all types of granules was
      satisfactory. Among the sustained-release granules, we selected granules with a
      content and a degree of sustained-release suitable for sustained-release
      suppositories.

PMID- 19182388
TI  - Pharmacokinetics of human immunodeficiency virus protease inhibitor, nelfinavir,
      in poloxamer 407-induced hyperlipidemic model rats.
AB  - The effect of hyperlipidemia (HL) on the pharmacokinetics of nelfinavir (NFV), a
      human immunodeficiency virus protease inhibitor, was investigated, focusing on
      the change of NFV distribution in plasma using poloxamer 407-induced HL model
      rats (HL rats). The plasma unbound fraction (f(u)) in HL rats (0.20-0.39%) was
      significantly lower than the control (0.92-1.47%). Lipoprotein level in HL rats
      was about 5 times higher and low- and very low-density liproteins ratio were 1.7
      4.5 times higher than the control. NFV recovery in the triglyceride-rich
      lipoprotein such as chylomicron, low- and very low-density liproteins fractions
      of HL rats were significantly higher. The area under the plasma concentration
      time curve (AUC) of NFV after intravenous (i.v.: 5 mg/kg) and intraduodenal
      (i.d.: 30 mg/kg) administration to HL rats (i.v.: 6.12+/-0.48, i.d.: 24.4+/-2.2
      microg x h/ml) were higher than the control (i.v.: 1.62+/-0.21, i.d.: 5.00+/-0.36
      microg x h/ml). The steady state volume of distribution (Vd(ss)) in HL rats
      (0.60+/-0.07 l/kg) was lower than the control (6.25+/-0.55 l/kg). Systemic
      availability (F) in HL rats (66.6%) was higher than the control (51.4 %).
      Directly absorbed NFV from the gastrointestinal tract to the lymphatic system in
      HL rats was about 2 times higher than the control. From the results of this
      study, it was concluded that the increase of AUC was caused by decreasing f(u)
      and Vd(ss) due to the increase of the triglyceride-rich lipoprotein level. In
      addition, it was suggested that the increase of absorbed NFV through the
      lymphatic system, which did not receive the first-pass effect, was one reason for
      the increase of F in HL rats.

PMID- 19182390
TI  - Improving the stability of short hairpin RNA against fetal bovine serum using the
      third double-stranded RNA-binding domain from Staufen protein.
AB  - RNA interference (RNAi) is a technology that specifically inhibits gene
      expression and is carried out by small 21-27-nucleotide double-stranded small
      interfering RNA (siRNA) or short hairpin RNA (shRNA). RNAi has become a very
      promising technology for genetic research, however problems remain with the
      delivery of siRNA into cells. SiRNA and shRNA are easily degraded by RNases in
      body fluids and are hardly able to permeate cell membranes because of
      hydrophilic, polyanionic macromolecules which make their bioavailability very
      low. We have focused on the third double-stranded RNA-binding domain (dsRBD3)
      from the Mus musculus Staufen protein in order to develop a non-viral,
      multifunctional, artificial virus-like delivery system. We constructed a dsRBD3
      expression vector and the recombinant dsRBD3 was expressed as a fusion protein
      with affinity tags. Purified dsRBD3 was mixed with siRNA or shRNA at various
      ratios and then added to fetal bovine serum (FBS) to evaluate the inhibition of
      the degradation of double-stranded RNA (dsRNA) by RNase. Unexpectedly, dsRBD3 was
      not able to protect the siRNA against degradation by FBS, but shRNA was
      stabilized to some degree by dsRBD3.

PMID- 19182391
TI  - Developmental changes in serotonin 2C receptor mRNA editing in the rat cerebral
      cortex and primary cultured cortical neurons.
AB  - Serotonin 2C receptor (5-HT2CR) mRNA has been reported to receive editing at 5
      nucleotide positions (named sites A-E) which are located inconsecutively on the
      nucleotide sequence encoding the 2nd intracellular loop of the receptor protein.
      To clarify the physiological role of 5-HT2CR mRNA editing, we investigated
      developmental changes in editing frequencies at sites A-E in the rat cerebral
      cortex and primary cultured cortical neurons. The editing at sites A and B
      increased in parallel with the rat brain development and reached a plateau of 80
      100% frequency at postnatal days 1-3. Although editing frequency at site C was
      low compared to those detected at other sites except site E during a
      developmental period, it reached the maximal value of 30% during a first 7-d
      period after birth and then decreased gradually to the negligible level at PN49.
      Site D exhibited almost constant susceptibility (about 60%) to editing, while no
      editing at site E was occurred during rat brain development. Similar changes
      during development in editing frequencies at these sites were observed in primary
      cultured cortical cells during the cultivation period. These findings indicated
      that editing sites A-D on 5-HT2CR mRNA have different susceptibility and that the
      frequencies at these sites are not always constant during development.

PMID- 19182392
TI  - Mu-opioid and N-methyl-D-aspartate receptors are localized at laryngeal
      motoneurons of guinea pigs.
AB  - The glottic movement is important for generating efficient airflow in respiration
      and related reflexes such as coughing. The superior laryngeal nerve (SLN)
      innervates the cricothyroid muscle and regulates the glottic aperture. A total of
      620 laryngeal motoneurons (LMNs) providing efferent fibers to the SLN were
      retrogradely identified with fluorescent wheat germ agglutinin (WGA) in 8 guinea
      pigs. The WGA-labeled cells were distributed in the ventrolateral part of nucleus
      ambiguus, extending 1.8-2.2 mm lateral to the midline, 0.8-1.2 mm from the
      ventral surface and 1.7-2.6 mm rostral to the obex. Double staining revealed that
      28.4% of LMNs (44 out of 155 cells examined) were immunopositive to N-methyl-D
      aspartate (NMDA) receptors and 29.2% of LMNs (55 out of 185 cells) to mu-opioid
      receptors. The present study demonstrates phenotypic variation in the synaptic
      transmission to the LMNs in guinea pigs. These results suggest modulation of the
      glottic movement by mu-opioid and NMDA mechanisms.

PMID- 19182393
TI  - Effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor, on DNA
      dependent protein kinase.
AB  - Phosphatidylinositol 3-kinase (PI3K) has been implicated in a variety of diseases
      including cancer. A number of PI3K inhibitors have recently been developed for
      use in cancer therapy. ZSTK474 is a highly promising antitumor agent targeting
      PI3K. We previously reported that ZSTK474 showed potent inhibition against four
      class I PI3K isoforms but not against 140 protein kinases. However, whether
      ZSTK474 inhibits DNA-dependent protein kinase (DNA-PK), which is structurally
      similar to PI3K, remains unknown. To investigate the inhibition of DNA-PK, we
      developed a new DNA-PK assay method using Kinase-Glo. The inhibition activity of
      ZSTK474 against DNA-PK was determined, and shown to be far weaker compared with
      that observed against PI3K. The inhibition selectivity of ZSTK474 for PI3K over
      DNA-PK was significantly higher than other PI3K inhibitors, namely NVP-BEZ235, PI
      103 and LY294002. These results indicated that ZSTK474 was the most specific
      agent among these PI3K inhibitors.

PMID- 19182394
TI  - Phenylethylamide and phenylmethylamide derivatives as new tyrosinase inhibitors.
AB  - Increased production and accumulation of melanin lead to hyperpigmentation
      disorders. Several inhibitors of tyrosinase, the key enzyme in melanin synthesis
      have been developed but exhibited lack of efficiency or some adverse side
      effects. Therefore, it appears very important to find new agents that will be
      able to promote inhibition of tyrosinase and pigmentation. In this study, some
      phenylalkylcinnamide molecules were synthesized and evaluated for their ability
      to act as tyrosinase inhibitors. Compounds 2 (IC(50)=0.03 mM) and 12
      (IC(50)=0.028 mM) showed strong tyrosinase inhibitory potential comparable to
      standard hydroquinone (IC(50)=0.037 mM). Taken together, compounds 2 and 12 can
      be considered as good candidates for further investigations to evaluate their
      effect on the inhibition of melanin synthesis and skin pigmentation.

PMID- 19182395
TI  - Effect of gender on theophylline clearance in the asthmatic acute phase in
      Japanese pediatric patients.
AB  - The effect of gender on theophylline clearance was investigated retrospectively
      in 96 Japanese pediatric patients (63 males and 33 females) ranging in age from
      0.5 to 8 years and in weight from 6.3 to 36.8 kg. All patients received
      intravenous constant-rate infusion of aminophylline in the asthmatic acute phase.
      The theophylline clearances in males and females were 56.2+/-15.4 and 50.1+/-14.2
      ml/h/kg for ages 0.5-<2 years, 58.7+/-18.8 and 48.3+/-6.5 ml/h/kg for ages 2-<4
      years, and 65.7+/-12.0 and 52.1+/-16.8 ml/h/kg for ages 4-<9 years, respectively.
      At ages from 2 to 8 years, the theophylline clearance was 20% higher in males
      than in females (p<0.05). Our findings suggested that the initial dosage of
      theophylline should be adjusted according to the gender of pediatric patients and
      particularly in the case of infants.

PMID- 19182396
TI  - Effects of sesquiterpene lactones on melanogenesis in mouse B16 melanoma cells.
AB  - In this study, we examined the effect of sesquiterpene lactones isolated from
      Calea urticifolia and Tanacetum parthenium (feverfew) on melanogenesis in mouse
      B16 melanoma cells. In response to 3-isobutyl-1-methylxanthin (IBMX), B16
      melanoma cells underwent differentiation characterized by increased melanin
      biosynthesis. Treatment of sesquiterpene lactones at lower concentration (1
      microM) significantly blocked IBMX-induced melanogenesis, but did not induce the
      inhibitory activity of cell growth. Among them, 2,3-epoxyjuanislamin exhibited a
      potent inhibitory effect on melanogenesis. Treatment of B16 cells with 2,3
      epoxyjuanislamin elicited significant decreases in tyrosinase protein and mRNA
      levels. These results demonstrated that the inhibitory effects of sesquiterpene
      lactones on melanin biosynthesis may be due to the suppression of tyrosinase
      expression.

PMID- 19182397
TI  - Non-ionic surfactant modified cationic liposomes mediated gene transfection in
      vitro and in the mouse lung.
AB  - As reported previously, cationic liposomes formulated with
      dioleoylphosphatidylethanolamine (DOPE) and N,N-methyl hydroxyethyl aminopropane
      carbamoyl cholesterol (MHAPC-liposomes) achieved efficient gene transfection in
      the mouse lung following intratracheal injection. We have studied here the role
      of surfactants, mannosylerythritol lipid-A (MEL-A) and polysorbate 80 (Tween 80),
      in affecting gene transfection of MHAPC-lipoplexes (complex with pCMV-luc DNA) in
      A549 cells and in the mouse lung. MEL-A increased gene transfection of MHAPC
      lipoplexes significantly in vitro and slightly in the mouse lung, while Tween 80
      decreased it both in vitro and in vivo. As assessed by confocal laser scanning
      microscopy and fluorescence imaging, MEL-A might faciliate gene dissociation from
      MHAPC-lipoplexes with fluorescein-labeled oligodeoxynucleotide (FITC-ODN) after
      internalization into the cells and retained the lipoplexes in the mouse lung for
      prolonged time, while Tween 80 was inefficient to deliver foreign gene into
      target cells and in the lung. These results demonstrated that MEL-A is
      advantageous to Tween 80 in the modification of cationic liposomes as gene
      delivery vectors in the lung.

PMID- 19182398
TI  - Application of a continuous square-wave potential program for sub nano molar
      determination of ketotifen.
AB  - An electroanalytical method has been developed for the determination of the
      ketotifen by continuous square wave adsorptive stripping voltammetry on a ultra
      gold microelectrode (Au UME) in aqueous solution with phosphate buffer as
      supporting electrolyte. The best adsorption conditions were found to be pH 2.3,
      an accumulation potential of 300 mV (Au vs. Ag: AgCl-KCl 3 M) and an accumulation
      time of 400 ms. Variation of admittance in the detection process is created by
      inhibition of oxidation reaction of the electrode surface, by adsorption of
      ketotifen. Furthermore, signal-to-noise ratio was significantly increased by
      application of discrete fast Fourier transform (FFT) method, background
      subtraction and two-dimensional integration of the electrode response over a
      selected potential range and time window. Also in this work some parameters such
      as square-wave frequency, eluent pH, and accumulation time were optimized.
      Effects of square-wave frequency, step potential and pulse amplitude were
      examined for the optimization of instrumental conditions. The calibration curve
      is linear in the range 2.0x10(-7)---5.0x10(-12) M with a detection limit of
      2.0x10(-12) M (ca. 0.7 pg/ml). The method maybe applied direct determination of
      the drug in pharmaceutical and biological samples. For a concentration of 5.0x10(
      8) M a recovery value of 99.89% is obtained.

PMID- 19182399
TI  - Design and in vitro/in vivo evaluation of multi-layer film coated pellets for
      omeprazole.
AB  - The purpose of the study is to perform the in vitro and in vivo evaluation of
      multi-layer film coatings for omeprazole. The system consists of drug-layered or
      drug-containing core pellets coated with salt (sodium chloride and disodium
      hydrogen phosphate), hydroxypropyl methyl cellulose (HPMC), and enteric film
      coating layer, respectively. The drug-layered core pellets were prepared by a
      coating layer of omeprazole on inert pellet cores in fluidized bed coater. An in
      vitro/in vivo gastro-resistance study was conducted, and a dissolution study was
      performed in pH 7.4 phosphate buffer for omeprazole release. The multi-layer
      coated pellets were stable in gastric pH conditions and upper gastrointestinal
      (GI) tract in rats. Salt layer improved the drug stability, and its coating
      levels had little influence on the dissolution profiles of omeprazole. The rate
      of drug release was significantly delayed by HPMC layer. The salt layer could
      function as a separated layer, and substitute part of the HPMC layer and decrease
      the coating levels of HPMC. The bioavailability (AUC) of the multi-layer coated
      drug-layered and drug-containing pellets was 3.48+/-0.86 and 2.97+/-0.57
      microg*h/ml, respectively. The drug-layered pellets with multi-layer film
      coatings not only provided delayed and rapid release of omeprazole, but also
      could provide a good stable property for omeprazole. It was confirmed that rapid
      in vitro drug release rate resulted in better absorption.

PMID- 19182400
TI  - Adsorption properties of As(III) and Cr(VI) in water environment by calcined
      gibbsite.
AB  - The adsorption properties of As(III) and Cr(VI) by gibbsite (GB) calcined at 200
      to 1150 degrees C was investigated on basis of their specific surface area,
      number of hydroxyl groups, surface pH and adsorption isotherms. The amount of
      As(III) and Cr(VI) adsorbed on the calcined GB at 300 or 400 degrees C was the
      highest. In the case of the calcination temperature was more than 700 degrees C,
      the amount adsorbed decreased with the increasing calcination temperature. In a
      single solution system, the amount of As(III) adsorbed on calcined GB was higher
      than that of Cr(VI). The amount of As(III) and Cr(VI) adsorbed on calcined GB was
      higher in a binary solution system than those in a single solution system. The pH
      in solution after As(III) and Cr(VI) adsorption was greater than that before
      adsorption. These results indicated that the adsorption mechanism of As(III) and
      Cr(VI) was as followed: the hydroxyl groups on calcined GB were exchanged to
      As(III) and Cr(VI) and they adsorbed n the calcined GB surface. In the case of
      coexistence of As(III) and Cr(VI), they could be removed better by calcined GB
      because the pH in binary solution was lower than that in single solution. Both
      As(III) and Cr(VI) in water environment could be removed by the calcined GB
      simultaneously.

PMID- 19182401
TI  - Flavonoid and a rare benzophenone glycoside from the leaves of Aquilaria
      sinensis.
AB  - From the leaves of Aquilaria sinensis (LOUR.) GILG, a novel benzophenone
      glucoside, designated as aquilarinoside A (1), and a new flavonoid, as 7-beta-D
      glucoside of 5-O-methylapigenin (2), along with eight known compounds (3-10) were
      isolated. The structures of 1 and 2 were fully characterized by spectroscopic
      methods (1D, 2D NMR and MS) and the relative stereochemistry was assigned based
      on nuclear Overhauser effect spectroscopy (NOESY) correlations and analyses of
      coupling constants. The new compounds showed inhibition activity against
      polymorphonuclear neutrophils (PMNs) respiratory burst stimulated by PMA.

PMID- 19182402
TI  - Surface properties of lipoplexes modified with mannosylerythritol lipid-a and
      tween 80 and their cellular association.
AB  - The surface properties of cationic liposomes and lipoplexes largely determine the
      cellular association and gene transfection efficiency. In this study, we measured
      the surface properties, such as zeta potentials, surface pH and hydration levels
      of MHAPC- and OH-Chol-lipoplexes and their cellular association, without and with
      the modification of biosurfactant mannosylerythritol lipid-A (MEL-A) or Tween 80
      (MHAPC=N,N-methyl hydroxyethyl aminopropane carbamoyl cholesterol; OH
      Chol=cholesteryl-3beta-carboxyamindoethylene-N-hydroxyethylamine). Compared to OH
      Chol-lipoplexes, the higher cellular association of MHAPC-lipoplexes correlated
      with the significantly higher zeta potentials, lower surface pH levels and
      "drier" surface, as evaluated by the generalized polarization of laurdan. Both
      MEL-A and Tween 80 modification of MHAPC-lipoplexes did not significantly change
      zeta potentials and surface pH levels, while MEL-A modification of OH-Chol
      lipoplexes seriously decreased them. MEL-A hydrated the liposomal surface of
      MHAPC-lipoplexes but dehydrated that of OH-Chol-lipoplexes, while Tween 80
      hydrated those of MHAPC- and OH-Chol-lipoplexes. In all, cationic liposomes
      composed of lipids with secondary and tertiary amine exhibited different surface
      properties and cellular associations of lipoplexes, and modification with
      surfactants further enlarged their difference. The strong hydration ability of
      Tween 80 may relate to the low cellular association of lipoplexes, while the
      dehydration of MEL-A-modified OH-Chol-lipoplexes seemed to compensate the
      negative zeta potential for the cellular association of lipoplexes.

PMID- 19182403
TI  - Characterization of flavonoid metabolites in rat plasma, urine, and feces after
      oral administration of Semen Ziziphi Spinosae extract by HPLC-diode-array
      detection (DAD) and ion-trap mass spectrometry (MS(n)).
AB  - A highly specific and sensitive method using high performance liquid
      chromatography coupled with diode-array detection and ion-trap mass spectrometry
      (HPLC-DAD-MS(n)) was developed for study of the constituents of flavonoid extract
      of jujube seeds and the metabolites in rat plasma, urine, and feces samples after
      oral administration of flavonoid extract of jujube seeds. Two major flavonoids
      (spinosin and 6'''-feruloylspinosin) with content >60% in the flavonoid extract
      of jujube seeds were detected and confirmed by comparison with the reference
      standards. Furthermore, five metabolic components in plasma, seven in urine, and
      four in feces were detected and elucidated. The scientific and plausible
      biotransformation pathways of the main components in flavonoid extract of jujube
      seeds were also proposed, together with presentation of clues for potential
      bioactive mechanisms. This convenient HPLC-DAD-MS(n) method could be used to
      identify the chemical components of flavonoid extract of jujube seeds as well as
      their metabolites, and to reveal their possible metabolic mechanism of action in
      vivo.

PMID- 19182404
TI  - Nucleophilic activation of a tetra-substituted mitomycin cyclic bis-disulfide.
AB  - The multimerization of functional DNA alkylating agents has drawn significant,
      recent interest because these compounds are expected to generate enhanced levels
      of DNA cross-linked adducts, compared with their monomeric agents. Here we report
      the evaluation of 7-N,7'-N'-(1'',2'',9'',10''-tetrathia-cyclohexadecanyl
      3'',8'',11'',16''-tetramethylenyl)tetrakismitomycin C (8), in which four
      mitomycin units are attached to the novel bis-disulfide linker, 3,8,11,16
      tetrakis(aminomethyl)-1,2,9,10-tetrathia-cyclohexadecane. Compound 8 was designed
      to undergo preferential C(1) mitomycin activation under nucleophilic as well as
      under acidic and reductive conditions. We anticipated that treating 8 with
      nucleophiles would lead to bis-disulfide cleavage thus producing two mitomycin
      dimers (9) capable of generating DNA interstrand cross-links (ISC). The mitomycin
      units in 9 are tethered by a stable carbon backbone linkage. According to the
      procedure reported by Lee and coworkers (Tetrahedron, 61, 1749-1754 (2005)), we
      synthesized 8 and the reference mitomycin dimer, 7-N,7'-N'-(2'',7''-dihydroxy
      1'',8''-octanediyl)bismitomycin C (15). Compound 8 was activated under acidic
      conditions thereby generating mitosene product 16, in which all four mitomycin
      units within the 16-membered ring were activated. Using the nucleophile Et(3)P,
      we found that 8 underwent significantly enhanced mitosene production compared
      with its reference compound 15. We further demonstrated that under nucleophilic
      activation conditions 8 generated higher levels of DNA ISC than either 1 or 15.
      The cytotoxicities of 8 and 15 in a select tumor cell line were evaluated and
      compared with mitomycin C (1).

PMID- 19182405
TI  - New C(19)- and C(18)-diterpenoid alkaloids from Delphinium anthriscifolium var.
      savatieri.
AB  - Three new C(19)-diterpenoid alkaloids, anthriscifoldines A-C (1-3), and two new
      C(18)-diterpenoid alkaloids, anthriscifolcines F and G (5, 6), were obtained from
      the whole herbs of Delphinium anthriscifolium var. savatieri during our further
      investigation on a larger scale of recollected plants. Their structures were
      elucidated based on the interpretation of NMR and high-resolution ESI-MS data,
      and chemical transformation. In addition, five known C(19)-diterpenoid alkaloids
      were also isolated and identified as nudicaulamine (4), delbruninol (7),
      blacknine (8), winkleriline (9), and deltaline (10).

PMID- 19182406
TI  - Novel norhumulene and xeniaphyllane-derived terpenoids from a formosan soft coral
      Sinularia gibberosa.
AB  - A novel skeletal norhumulene (1) and six xeniaphyllane-derived compounds,
      including norditerpenoids (2, 3) and diterpenoids (4-7), were isolated from the
      EtOAc extract of the Formosan soft coral Sinularia gibberosa. Their structures
      were elucidated by spectroscopic analysis. In vitro cytotoxic evaluation of the
      above metabolites revealed that 2 and 4 showed weak cytotoxicity toward a few
      cancer cell lines.

PMID- 19182407
TI  - Conversion of 4-oxoproline esters to 4-substituted pyrrole-2-carboxylic acid
      esters.
AB  - The Grignard, Wittig, Tebbe, Horner-Emmons, and Reformatsky reactions of the 4
      oxoproline esters gave the corresponding 4-alylated or 4-alkylidenated products,
      respectively. The products were properly treated with bases to cause
      aromatization, giving 4-substituted pyrrole-2-carboxylic acid esters such as
      methyl 4-methylpyrrole-2-carboxylate, which is a trail pheromone of Atta texana.

PMID- 19182408
TI  - Acylated-oxypregnane glycosides from the roots of Asclepias syriaca.
AB  - Twenty new pregnane glycosides were obtained from the roots of Asclepias syriaca
      L. (Asclepiadaceae). These glycosides were confirmed to contain ikemagenin, 12-O
      nicotinoyllineolon, 5alpha,6-dihydroikemagenin, and 12-O-tigloylisolineolon, as
      their aglycones, using both spectroscopic and chemical methods.

PMID- 19182409
TI  - Isolation and structural elucidation of cyclopentynafil and N-octylnortadalafil
      found in a dietary supplement.
AB  - A new sildenafil analogue, cyclopentynafil (1) and a new tadalafil analogue, N
      octylnortadalafil (2) were isolated from a dietary supplement illegally marketed
      for erectile dysfunction. The structures of the sildenafil and tadalafil
      analogues were elucidated by using HPLC-photodiode array (PDA), LC-MS, high
      resolution MS, NMR and circular dichroism (CD). These compounds were determined
      to be 5-[2-ethoxy-5-(4-cyclopentylpiperazin-1-ylsulfonyl)phenyl]-1-methyl-3
      propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one and (6R,12aR)-2-octyl-6-(1,3
      benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole
      1,4-dione, respectively. Recently, a large number of phosphodiesterase-5 (PDE-5)
      inhibitors, including their analogues, have been isolated from dietary
      supplements, while cyclopentynafil and N-octylnortadalafil are the first
      compounds reported to be new sildenafil and tadalafil analogues, respectively.
      Quantitative HPLC analysis showed that the contents of 1 and 2 in the product
      were about 130 mg/tablet (301 microg/mg) and about 27 mg/tablet (64.1 microg/mg),
      respectively.

PMID- 19182410
TI  - Structure-activity relationship of bis-galloyl derivatives related to (-)
      epigallocatechin gallate.
AB  - Green tea and (-)-epigallocatechin gallate (EGCG: one of main components of green
      tea) are well known to have preventive activities against human cancers.
      Previously, using a galloyl group as a core structure derived from EGCG, we
      developed alkyl gallate and gallamide derivatives, which showed strong
      antiproliferative activity towards human leukemia HL-60 cells by inducing
      apoptosis. Here, as a further structural development study, we planned to
      introduce an additional galloyl group into alkyl gallates and gallamides.
      According to this strategy, various bisgallate and bisgallamide derivatives were
      synthesized and tested for antiproliferative activity towards HL-60 cells. In
      gallamide derivatives having a short alkyl chain, the additional galloyl group
      enhanced the antiproliferative activity. In contrast, in the gallate derivatives,
      the additional galloyl group had no effect on the antiproliferative activity.

PMID- 19182411
TI  - Four new triterpenes from fungus of Fomes officinalis.
AB  - In the previous work we reported five lanostane-type triterpenes from the CHCl(3)
      soluble fraction of Fomes officinalis. In further study on the isolation of
      constituents from the CHCl(3) soluble fraction, four new triterpenes,
      fomefficinic acids F (1), G (2) and fomefficinols A (3), B (4), together with
      seven known compounds officinalic acid (5), fomlactone A (6), fomlactone B (7),
      fomlactone C (8), laricinolic acid (9), ergosterol (10), ergota-7,22,dien-3beta
      ol (11) were isolated. The structures of new compounds were determined by
      spectroscopic analyses and chemical methods including NMR spectroscopic
      techniques ((13)C, (1)H, heteronuclear multiple quantum coherence (HMQC),
      heteronuclear multiple bonding correlation (HMBC), correlation spectroscopy
      (COSY) and nuclear Overhauser effect spectroscopy (NOESY)).

PMID- 19182412
TI  - Structures of acetylated oleanane-type triterpene saponins, rarasaponins IV, V,
      and VI, and anti-hyperlipidemic constituents from the pericarps of Sapindus
      rarak.
AB  - The methanolic extract and its saponin fraction (methanol-eluted fraction) of the
      pericarps of Sapindus rarak DC. were found to suppress plasma triglyceride
      elevation in olive oil-treated mice. From the active fraction, three new acylated
      oleanane-type triterpene saponins, rarasaponins IV (1), V (2), and VI (3), were
      isolated. The structures of 1-3 were elucidated on the basis of chemical and
      spectroscopic evidence. The principle saponin constituents, hederagenin 3-O-alpha
      L-arabinopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranoside (4) and hederagenin 3-O-(3,4-di-O-acetyl-alpha-L
      arabinopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranoside (5), showed inhibitory effects on plasma triglyceride elevation
      at a dose of 200 mg/kg, per os.

PMID- 19182413
TI  - Isolation and structure of hematoside-type ganglioside from the starfish Linckia
      laevigata.
AB  - A hematoside-type ganglioside, LLG-1 (1), has been obtained from the polar lipid
      fraction of the chloroform/methanol extract of the starfish Linckia laevigata.
      The structure of the ganglioside has been determined on the basis of chemical and
      spectroscopic evidence as 1-O-[N-glycolyl-alpha-D-neuraminosyl-(2-->3)-beta-D
      galactopyranosyl-(1-->4)-beta-D-glucopyranosyl]-ceramide. The ceramide moiety was
      composed of heterogeneous 2-hydroxy fatty acid and phytosphingosine units. This
      is the first report on the isolation and structure elucidation of naked
      hematoside-type ganglioside from echinoderms.

PMID- 19182414
TI  - New flavonoid glycosides and cyanogenic glycosides from Dracocephalum peregrinum.
AB  - Separation of ethyl acetate fractionation of Dracocephalum peregrinum afforded
      three new flavonoid glucosides (1-3), and a new cyanogenic glucoside (4). Their
      structures were elucidated based on HR-electron spray ionization (ESI)-MS, EI-MS,
      UV, IR, 1D-, and 2D-NMR data. 1-4 were tested in vitro for their antiinflammatory
      activity against the RAW 264.7, 293 cells. Among the compounds tested, 1-4 shown
      good antiinflammatory activity at 100 mug/ml by the measurement of nitric oxide
      (NO) in lipopolysaccharide (LPS) activated macrophages. But only 2 and 3 shown
      weak antiinflammatory activity at 100 mug/ml during the nuclear factor (NF)
      kappaB activation assay.

PMID- 19182415
TI  - Deprotection of the indole (N(ind))-formyl (For) group on tryptophan employing a
      new reagent, N,N'-dimethylethylendiamine (DMEDA) in an aqueous solution.
AB  - The deprotection of the indole (N(ind))-formyl (For) group on Trp was achieved in
      a 95% yield using N,N'-dimethylethylendiamine (DMEDA) (1.5, 2.0, 3.0 eq) in water
      at room temperature. A new reagent was successfully applied to the deprotection
      of a model peptide, H-Phe-Trp(N(ind)-For)-Lys-Tyr-OH, to give H-Phe-Trp-Lys-Tyr
      OH in a 91% yield.

PMID- 19182416
TI  - Synthesis, cytotoxic and antimicrobial screening of a proline-rich
      cyclopolypeptide.
AB  - Present study describes the first total synthesis of a cyclic heptapeptide,
      stylisin 1 (8) via coupling of tetrapeptide Boc-L-tyrosinyl-L-prolyl-L-leucyl-L
      proline-OH and tripeptide L-phenylalanyl-L-isoleucyl-L-proline-OMe followed by
      cyclization of linear heptapeptide segment. Structure elucidation of synthesized
      cyclopeptide was done on basis of detailed spectral as well as elemental
      analysis. From the results of pharmacological screening, it was concluded that
      cyclopeptide 8 possessed moderate cytotoxicity against Dalton's lymphoma ascites
      (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines with IC(50) (inhibitory
      concentration, 50%) values of 10.6 and 14.6 microM. Furthermore, cyclopeptide 8
      exhibited moderate to good antimicrobial activity against Gram -ve (negative)
      bacteria Klebsiella pneumoniae and Pseudomonas aeruginosa, dermatophytes and
      Candida albicans with minimum inhibitory concentration (MIC) of 6 microg/ml.

PMID- 19182417
TI  - Three new bibenzyl derivatives from Dendrobium candidum.
AB  - Three new compounds were isolated from the stems of Dendrobium candidum: (S)
      3,4,4'-trihydroxy-5,alpha-dimethoxybibenzyl (1), named dendrocandin C; (S)-3,4,4'
      trihydroxy-5-methoxy-alpha-ethoxybibenzyl (2), named dendrocandin D; and
      3,3',4,4'-tetrahydroxy-5-methoxybibenzyl (3), named dendrocandin E. Their
      structures were elucidated by 1D- and 2D-NMR spectroscopy and mass spectroscopy.
      The isolated compounds exhibited potent antioxidant activity in the 1,1-diphenyl
      2-picrylhydrazyl (DPPH) radical scavenging test, with IC(50) values of 34.2,
      34.5, and 15.6 microM for compounds 1, 2, and 3, respectively. Vitamin C was used
      as positive control with IC(50) 23.2 microM.

PMID- 19182418
TI  - Cytotoxic sorbicillinoids and bisorbicillinoids from a marine-derived fungus
      Trichoderma sp.
AB  - Four sorbicillinoids (1-4) and seven bisorbicillinoids (5-11), including two new
      compounds, 6-demethylsorbicillin (1) and 10,11-dihydrobisvertinolone (6), were
      isolated from a marine-derived fungus Trichoderma sp. Their cytotoxic activities
      against HL-60 cell line were evaluated by Sulforhodamine B (SRB) assay method and
      flow cytometric analysis.

PMID- 19182419
TI  - Interaction of polyphenols with proteins: binding of (-)-epigallocatechin gallate
      to serum albumin, estimated by induced circular dichroism.
AB  - The binding of (-)-epigallocatechin gallate (EGCG), a representative natural
      polyphenol, to human serum albumin (HSA) and bovine serum albumin (BSA) was
      investigated using induced circular dichroism (CD). The site of the binding EGCG
      HSA was analyzed based on the competition with drugs with known binding sites on
      HSA, such as phenylbutazone (PB) and diazepam (DP). Double-reciprocal plot
      analyses showed the competitive relations with the site-I- (PB and tolbutamide,
      TB) and site-II-binding drugs (DP and ibuprofen, IP) indicating the binding of
      EGCG to sites I and II on HSA, while digitoxin (DG), a site-III-binding drug, did
      not affect the binding of EGCG. In an analogous way, the competitive relations
      were observed between EGCG and the site-I- (PB and TB) and site-II-binding
      (ethacrynic acid, EA) drugs for the binding of EGCG and BSA. The site-III drug DG
      also showed competitive binding with EGCG to BSA. The binding of EGCG to the
      albumins indicated its affinity to sites I and II on HSA, while competitive
      binding for all three sites was observed on BSA.

PMID- 19182420
TI  - Life style-related disease and colorectal cancer.

PMID- 19182421
TI  - Modifiable risk factors for colorectal neoplasms and hyperplastic polyps.
AB  - PURPOSE: Obesity, smoking and alcohol are modifiable putative risk factors for
      colorectal neoplasms (CRN) and hyperplastic polyps (HP). The aim of this study
      was to evaluate the strength of association between these modifiable risk factors
      and colorectal polyps. METHODS: These risk factors were assessed by using a
      questionnaire completed by the patient prior to colonoscopy. Eight hundred
      seventy consecutive patients satisfying inclusion criteria who had undergone a
      complete colonoscopy were divided into 4 groups: CRN (n=194), HP (n=132), CRN and
      HP (n=42) and control (neither CRN nor HP; n=586). Multiple logistic regression
      was performed. RESULTS: The ORs [95%CI] of both CRN and HP for incremental body
      mass index expressed in 2 categories (>or=22, >or=25) were 2.12 [1.00, 4.50] and
      1.41 [0.53, 3.77], respectively. The ORs [95%CI] of CRN and HP for heavy smoking
      of over 20 pack-years were 1.66 [1.05, 2.64] and 1.67 [1.01, 2.77], respectively.
      The ORs of CRN and HP for habitual alcohol drinking (median ethanol intake 32
      g/day and interquartile range 18-40 g/day) were 1.31 [0.86, 1.98] and 1.91 [1.06,
      3.47], respectively. CRN and HP were correlated with each other (p=0.0043, chi
      square test). Aging was a significant risk factor for all three groups of
      colorectal polyps. CONCLUSION: These findings are especially important since
      smoking and alcohol consumption are modifiable risk factors. Heavy smokers should
      be encouraged to quit to reduce their risk of CRN and HP. Habitual drinkers
      should be warned of the risk of HP. HP can be a marker of coincidence of CRN.

PMID- 19182422
TI  - Effectiveness of meropenem for the treatment of aspiration pneumonia in elderly
      patients.
AB  - OBJECTIVE AND BACKGROUND: In Japan, an increase in the elderly population is
      associated with an increased incidence of aspiration pneumonia. Treatment
      guidelines for aspiration pneumonia recommend the use of antibiotics effective
      against anaerobic bacteria, such as carbapenems. However, the role of anaerobic
      bacteria in aspiration pneumonia and the clinical efficacy of meropenem in
      elderly aspiration pneumonia patients have only begun to be investigated.
      METHODS: A prospective study of 62 elderly hospitalized patients with aspiration
      pneumonia (34 males, 28 females; mean age 86.6 years) was conducted. The
      causative organisms of aspiration pneumonia, including anaerobic bacteria, were
      investigated using fiberoptic bronchoscopy. In addition, the efficacy and safety
      of intravenous meropenem for this treatment of this condition were evaluated.
      RESULTS: When disease severity was classified according to the Japanese
      Respiratory Society (JRS) guidelines, 80.7% of the cases in this study were
      graded as "most severe". The overall detection rate of bacteria was 87.1%
      (monomicrobial, 32.3%; polymicrobial, 54.8%). Of the 111 pathogens detected (14
      anaerobic pathogens remained unidentified), anaerobic bacteria accounted for
      19.8% and gram-negative enteric bacilli made up 19.8%. The overall clinical
      efficacy rate of meropenem therapy (1.0 g/day) was 61.3%. The mortality rate was
      9.7%, and anaerobic bacteria coexisted with aerobic bacteria in 66.7% of the
      patients who died. CONCLUSION: The use of antibiotics effective against anaerobic
      bacteria may be necessary for patients with potentially fatal aspiration
      pneumonia. Meropenem therapy for aspiration pneumonia is clinically effective and
      tolerable in elderly patients.

PMID- 19182423
TI  - Clinical evaluation of the T-SPOT.TB test for patients with indeterminate results
      on the QuantiFERON TB-2G test.
AB  - OBJECTIVE: To evaluate the clinical utility of the T-SPOT.TB test for patients
      with indeterminate results on the QFT-2G test. MATERIALS AND METHODS: Forty
      patients (10.6%) showed indeterminate results among 378 patients who underwent
      QFT-2G test because active TB disease was clinically suspected. T-SPOT.TB test
      was performed for these 40 patients before the initiation of antituberculous
      treatment. RESULTS: Forty patients (10.6%) were judged as showing indeterminate
      results on QFT-2G test because the positive control presented a lower IFN-gamma
      level. Elderly patients (68.2 versus 57.7) or immunocompromised patients
      receiving immunosuppressive treatments and patients with a decrease in lymphocyte
      count, serum protein and albumin were more frequently recognized in the patients
      with indeterminate results compared to those with determinate results on QFT-2G
      test. T-SPOT.TB test could clearly demonstrate the results in 26 of the 40
      patients (65.0%) with indeterminate results of QFT-2G test; these were divided
      into six patients with positive results and 20 with negative results of T-SPOT.TB
      test. Elderly patients (73.5 versus 64.3) or patients with underlying diseases
      such as malignant disease and those receiving immunosuppressive treatment and
      patients with hyponutritional conditions were more frequently recognized in the
      patients with indeterminate results compared to patients with determinate results
      on both tests. CONCLUSION: We think it may be necessary to introduce T-SPOT.TB
      test to increase the diagnostic rate of TB disease including latent tuberculosis
      infection because indeterminate results of QFT-2G test might be further decreased
      using T-SPOT.TB test. Although 14 patients showed indeterminate results on both
      tests, the lymphocytes of these patients may not possess functional cytokine
      production activity.

PMID- 19182424
TI  - Pancreatic carcinoma associated with portal vein tumor thrombus: three case
      reports.
AB  - Pancreatic carcinoma associated with portal vein tumor thrombus (PVTT) is rare.
      Here, we report three cases of resected pancreatic carcinoma associated with
      PVTT. In all three cases, preoperative images obtained using computed tomography
      and endoscopic ultrasonography revealed a tumor thrombus in the portal vein,
      which was connected to an irregular mass in the pancreas. All cases underwent
      surgical resection of the primary lesion and the PVTT. The pathological diagnoses
      of the tumors were two cases of tubular adenocarcinoma and one case of
      nonfunctioning endocrine carcinoma. We also retrospectively examined other
      patients who underwent surgical excision with portal vein resection.

PMID- 19182425
TI  - Advanced gastric cancer patient with peritonitis carcinomatosa successfully
      treated with a combination therapy of paclitaxel and TS-1, but relapsed with
      multiple bone metastasis and died from rapidly progressive meningitis
      carcinomatosa--advanced gastric cancer with metachronous peritonitis
      carcinomatosa and meningitis carcinomatosa.
AB  - A 59-year-old man diagnosed as gastric cancer with peritonitis carcinomatosa was
      treated with paclitaxel and TS-1; 60 mg/m(2)/day of paclitaxel was given on days
      1 and 8, and 60-80 mg/m(2)/day of TS-1 was given for 2 weeks. Six courses of
      combination therapy were administered, and the ascites disappeared completely.
      Because multiple bone metastases occurred, we attempted combination therapy with
      cisplatin and irinotecan hydrochloride; 50 or 30 mg/m(2)/day of cisplatin was
      given on day 1 or day 15, and 70 mg/m(2)/day of irinotecam hydrochloride was
      given on days 1 and 15. The patient achieved a remarkable response, however,
      intrameningeal dissemination occurred and he died from rapidly progressive
      meningitis carcinomatosa.

PMID- 19182426
TI  - Membranoproliferative glomerulonephritis-like glomerular disease and concurrent
      tubulointerstitial nephritis complicating IgG4-related autoimmune pancreatitis.
AB  - Autoimmune pancreatitis is characterized by diffuse enlargement of the pancreas,
      irregular narrowing of the pancreatic duct, high serum levels of IgG4, and
      lymphoplasmacytic infiltration in the pancreatic parenchyma. Accumulating
      evidence suggests that this autoimmune disease could present with diffuse
      infiltration of IgG4-positive plasmacytes in multiple organs. Recently, a new
      concept of IgG4-related systemic disease including autoimmune pancreatitis,
      characterized by high serum IgG4 level and tissue infiltration by IgG4-positive
      plasma cells, has been proposed. Renal lesions in IgG4-related diseases have been
      reported recently. Most of them are tubulointerstitial nephritis; however,
      glomerulonephritis associated with IgG4-related diseases is very rare. We
      describe here a patient with membranoproliferative glomerulonephritis-like
      glomerular disease, together with tubulointerstitial nephritis, idiopathic
      thrombocytopenic purpura, and autoimmune pancreatitis. An 80-year-old Japanese
      man was referred to our hospital with a 14-month history of proteinuria, and a
      progressively rising serum creatinine level. Renal biopsy revealed
      membranoproliferative glomerulonephritis-like glomerular disease and concurrent
      tubulointerstitial nephritis. Immunolabeling of renal tissue showed numerous IgG4
      positive plasma cells in the interstitium. The rare association between
      glomerulonephritis and IgG4-related systemic disease is discussed.

PMID- 19182427
TI  - Polymyositis with atypical pathological features associated with thymic
      carcinoma.
AB  - A 66-year-old man was admitted for progressive proximal weakness and myalgia in
      his shoulder girdles without skin lesions. A muscle biopsy showed infiltration of
      inflammatory cells, degeneration of muscle fibers, and perifascicular atrophy.
      Remarkably, MHC-I antigen was expressed in the muscle membrane and most of the
      inflammatory cells were CD8-positive, suggesting that class-I antigen-dependent
      cytotoxic T-cells played a crucial role in the muscle pathology, which supported
      a diagnosis of polymyositis rather than dermatomyositis. Magnetic resonance
      imaging of his chest revealed two mediastinal tumors, which were extirpated and
      diagnosed as thymic carcinoma. The muscle weakness was completely recovered after
      the operation and subsequent administration of oral prednisolone. Postoperative
      clinical improvement and decline of serum creatinine kinase suggested a
      paraneoplastic nature of the polymyositis in this patient.

PMID- 19182428
TI  - Mediastinal testicular tumor compressing the left atrium in a young male
      presenting initially with symptoms of left heart failure.
AB  - Extrinsic left atrial compression is an uncommon source of hemodynamic compromise
      that can be caused by many mediastinal structures including bronchogenic cysts,
      carcinoma, lymphoma, thymoma, aortic aneurysm and diaphragmatic hernia. We
      describe an unusual case of a 26-year-old man presenting with symptoms of left
      heart failure. Transthoracic echocardiography demonstrated extrinsic left atrial
      compression caused by a metastatic testis non-seminomatous germ cell tumor.
      Compression of the left atrium caused impaired left atrial filling, leading to
      pulmonary venous hypertension and pulmonary edema. To our knowledge, the present
      case is the first reported case of mediastinal metastatic testis non-seminomatous
      germ cell tumor causing symptoms of left heart failure by externally compressing
      the left atrium.

PMID- 19182429
TI  - Acute myocardial infarction due to aortic dissection.

PMID- 19182430
TI  - Linear medullary pericanal lesion with longitudinal myelitis can be diagnostic of
      neuromyelitis optica.

PMID- 19182431
TI  - Diabetes and hypertriglyceridemia modify the mode of acetaminophen-induced
      hepatotoxicity and nephrotoxicity in rats and mice.
AB  - Certain disease conditions can modify drug-induced toxicities, which, in turn,
      may cause a medication-related health crisis. Therefore, preclinical
      investigations into the alterations in drug-induced toxicities using appropriate
      disease animal models are very important. This paper reviews the reported data
      related to the effects of diabetes and hypertriglyceridemia, common lifestyle
      related diseases in a modern society, on acetaminophen (APAP)-induced
      hepatotoxicity and nephrotoxicity in rats and mice. It has generally been
      reported that diabetes protects rats and mice from APAP-induced hepatotoxicity
      and there are several reports that help to speculate on the effects of diabetes
      on APAP-induced nephrotoxicity. In fructose-induced hypertriglyceridemic rats,
      hepatotoxicity of APAP becomes apparently less severe, whereas nephrotoxicity of
      APAP becomes significantly more severe. The mechanisms of alteration of APAP
      induced hepatorenal toxicity under diabetic and hypertriglyceridemic conditions
      are also discussed in this paper.

PMID- 19182433
TI  - Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats.
AB  - Estimation of liver damage is important in the pathophysiological and
      toxicological study of liver disease. As a novel, non-invasive marker of liver
      damage, we studied the efficacy of urine bile acids (UBA) in a rat model of liver
      disease. Thioacetamide (TAA)-treated rats were used in this study. Single
      intraperitoneal administration of high-dose TAA induces severe damage to the
      liver, and thus is used as a model of acute hepatitis. Continuous administration
      of low-dose TAA yields mild damage to the liver, and induces cirrhosis and
      hepatic tumors. In this study, it was found that both acute and chronic
      administration of TAA was associated with a dose-dependent elevation of UBA. The
      elevation of UBA content correlated with the alteration of blood biochemical
      indicators, and UBA screening showed a remarkable ability to distinguish liver
      damaged rats from healthy rats. In particular, UBA analysis was found to have
      high sensitivity, specificity, and positive predictive value for the screening of
      rats with abnormal serum alkaline phosphatase (ALP) activity due to chronic liver
      damage, which was confirmed to include cholestasis and subsequent cirrhosis by
      liver histological analysis. In conclusion, we demonstrated that measurement of
      UBA is a simple, non-invasive and effective method for the screening of
      cholestasis in TAA-treated rats. We suggest that UBA analysis may have potent
      applicability for monitoring the progress of liver damage in animal models of
      chronic liver disease, such as cirrhosis and hepatic encephalopathy.

PMID- 19182432
TI  - Multiphoton spectral analysis of benzo[a]pyrene uptake and metabolism in breast
      epithelial cell lines.
AB  - Quantification of polycyclic aromatic hydrocarbons (PAH) and their metabolites
      within living cells and tissues in real time using fluorescence methods is
      complicated due to overlaping excitation and/or emission spectra of metabolites.
      In this study, simultaneous analysis of several metabolites of a prototype
      carcinogenic PAH, benzo[a]pyrene (BaP) in undifferentiated (MCF10A) and
      differentiated (MCF10CA1h) breast cancer cells was performed using single-cell
      multiphoton spectral analysis. The two cell types were selected for this study
      because they are known to have differences in BaP uptake and metabolism and
      induction of aryl hydrocarbon receptor-dependent ethoxyresorufin-O-deethylase
      (EROD) activity. Multiphoton microscopy spectral analysis performed in cells
      exposed to BaP for 24 hr identified 5 major peaks of fluorescence that were
      monitored within spectral bands. A comparison of the fluorescence peaks within
      these bands to those of BaP metabolite standards indicated that a peak in the
      spectral range of 393-415 nm matched benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10
      epoxide(+/-),(anti) (BPDE), the ultimate carcinogenic BaP metabolite. In
      addition, the 426-447 nm band matched the major metabolites 3
      hydroxybenzo[a]pyrene (3-OH BaP) and 9-hydroxybenzo[a]pyrene (9-OH BaP); the 458
      479 nm band corresponded to the secondary metabolite benzo[a]pyrene-3,6-dione
      (3,6 BPQ); and a peak at 490-530 nm matched the parent compound, BaP. Multiphoton
      spectral analysis also revealed differences in fluorescence intensities between
      MCF10A and MCF10CA1h cells within three spectral bands: 393-415 nm, 426-447 nm
      and 458-479 nm which were partially reversed with cyclosporine A suggesting
      differences in efflux mechanisms between cell lines. These results demonstrate
      the feasibility of analyzing BaP metabolism in situ by multiphoton spectral
      analysis and also identifying cell-type differences in BaP accumulation and
      metabolism.

PMID- 19182434
TI  - Application of an indwelling vascular access port for intravenous administration
      in a repeated and intermittent dose toxicity study in rats.
AB  - Totally implantable catheter animal models are considered useful for
      pharmacological and toxicological studies. In this report, we assessed the
      feasibility of using an indwelling vascular access port (VAP) in rats for long
      term evaluation of repeated and intermittent dose toxicity studies. In Experiment
      1, the VAP devices were implanted in male and female rats and a saline solution
      administered intravenously via the posterior vena cava for 2 weeks (4 ml/kg, 2
      ml/min, 5 times/week, 10 times total). General conditions, body weight and blood
      chemistry showed no toxicological changes compared with the rats in the non
      implanted, non-treated group. Hematology changes such as transient increases in
      peripheral blood reticulocytes and eosinophils were noted post-implantation. In
      pathology, proliferation of the endothelium at the site of VAP implantation and
      perivascular inflammatory cell infiltration including eosinophils in lung were
      noted at the end of the treatment period. Moreover, we found that the lumbar area
      is more suitable for VAP implantation than the back of neck for young, still
      growing rats. Experiment 2 included a 1-month intravenous intermittent dose (4
      ml/kg, 2 ml/min, 1 time/week, 5 times total) toxicity study in VAP-implanted rats
      followed by a 1-month recovery period conducted under Good Laboratory Practice
      (GLP) regulations. The results suggested that an animal model with implanted VAP
      is useful for intermittent intravenous dosing of drugs. Moreover, VAP
      implantation in animals is expected to be extrapolated to use VAP in humans in
      clinical studies.

PMID- 19182435
TI  - Enhanced hepatocarcinogenicity by combined inhalation and oral exposures to N,N
      dimethylformamide in male rats.
AB  - N,N-Dimethylformamide (DMF), a ubiquitous contaminant in living and working
      environments, enters the human body by inhalation, as well as by oral and dermal
      routes of exposure. In order to provide bioassay data for carcinogenic risk
      assessment of humans exposed to DMF by multiple routes of exposure,
      hepatocarcinogenic effect of combined inhalation and oral exposures of rats to
      DMF was examined. A group of 50 male F344 rats, 6-week-old, was exposed by
      inhalation to 0 (clean air), 200, or 400 ppm (v/v) of DMF vapor-containing air
      for 6 hr/day and 5 days/week during a 104-week period, and each inhalation group
      was given ad libitum DMF-formulated drinking water at 0, 800 or 1,600 ppm (w/w)
      for 104 weeks. Incidences of hepatocellular adenomas and carcinomas and their
      combined incidences were significantly increased in the combined-exposure groups
      compared with the untreated control group or each of the inhalation-alone and
      oral-alone groups with matching concentrations. Incidences of hepatocellular
      adenomas and carcinomas induced by the combined exposures were greater than the
      sum of the two incidences of the hepatocellular adenomas and carcinomas induced
      by the single-route exposures through inhalation and ingestion. The combined
      exposures enhanced tumor malignancy. It was concluded that the combined
      inhalation and oral exposures markedly enhance the incidences and malignancy of
      hepatocellular tumors, suggesting that the hepatocarcinogenic effect of the
      combined exposures is greater than the effect that would be expected under the
      assumption that the two effects of single-route exposures through inhalation and
      drinking are additive.

PMID- 19182436
TI  - Induction of mesothelioma by a single intrascrotal administration of multi-wall
      carbon nanotube in intact male Fischer 344 rats.
AB  - The present study assessed a carcinogenic hazard of multi-wall carbon nanotube
      (MWCNT) in intact (not genetically modified) rodents. MWCNT (1 mg/kg body weight,
      7 animals), crocidolite (2 mg/kg body weight, 10 animals) or vehicle (2%
      carboxymethyl cellulose, 5 animals) was administered to male Fischer 344 rats (12
      weeks old) by a single intrascrotal injection. Rats were autopsied immediately
      after death, when becoming moribund or at the end of the maximal observation
      period scheduled to be 52 weeks. After 37-40 weeks, however, 6 MWCNT-treated
      animals died or became moribund due to intraperitoneally disseminated
      mesothelioma (6/7, 85.7%) with bloody ascites. Peritoneal mesothelium was
      generally hypertrophic, and numerous nodular or papillary lesions of mesothelioma
      and mesothelial hyperplasia were developed. While mesothelioid cells were
      predominant in relatively early stage tumors, advanced stage mesotheliomas were
      constituted by 2 portions occupied by mesothelioid cells on the surface and
      spindle-shaped sarcomatous cells in the depth. In the latter, the histological
      transition was apparently observed between these 2 portions. Mesotheliomas were
      invasive to adjacent organs and tissues, and frequently metastasized into the
      pleura. Only 1 rat survived for 52 weeks in the MWCNT-treated group, and similar
      findings except mesothelioma were observed. All 10 crocidolite-treated and 5
      vehicle-treated rats survived for 52 weeks without any particular changes except
      deposition of asbestos in the former case. It is thus indicated that MWCNT
      possesses carcinogenicity causing mesothelioma at a high rate in intact male rats
      under the present experimental conditions. The present data identifies a
      carcinogenic hazard of MWCNT and will serve as one of the indispensable evidences
      to be used for the risk assessment crucial for not only protection and
      improvement of human health and welfare, but also safe and acceptable development
      and prevalence of this and similar upcoming materials.

PMID- 19182437
TI  - Green tea modulates reserpine toxicity in animal models.
AB  - Reserpine, a natural product extracted from Rauwolfia serpintina or Rauwolfia
      vomitoria, is a known dopamine depleter that inhibits several neurotransmitters.
      Reserpine has been used clinically to control hypertension, schizophrenia,
      insomnia and insanity. The use of this drug, however, has been limited because of
      its side effects which include oxidative damage to organs, including the liver.
      Green tea catechins are potent antioxidants that have the potential to counteract
      reserpine induced oxidative stress. This study investigated the merits of
      administering green tea concurrently with reserpine to prevent oxidative hepatic
      damage in Sprague-Dawely (SD) rats. Reserpine was found to cause hepatic damage,
      with elevated levels of oxidative stress markers, such as Thiobarbituric Acid
      Reactive Substances (TBARS), transaminases and cholesterol. Reserpine also
      induced hepatic ultra-structural damage in the cytoplasmic membrane, nuclear
      envelope, endoplasmic reticulum (rER), ribosomal stripping and mitochondria.
      Electron microscopy examination showed revival of liver cells as a result of
      green tea extract administration to experimental rats.

PMID- 19182438
TI  - Polymorphisms in the promoter region of the human class II alcohol dehydrogenase
      (ADH4) gene affect both transcriptional activity and ethanol metabolism in
      Japanese subjects.
AB  - Class II alcohol dehydrogenase (pi-ADH), encoded by alcohol dehydrogenase (ADH4),
      is considered to contribute to ethanol (EtOH) oxidation in the liver at high
      concentration. Four single nucleotide polymorphisms (SNPs) were found in the
      promoter region of this gene. Analysis of genotype distribution in 102 unrelated
      Japanese subjects revealed that four loci were in strong linkage disequilibrium
      and could be classified into three haplotypes. The effects of these polymorphisms
      on transcriptional activity were investigated in HepG2 cells. Transcriptional
      activity was significantly higher in cells with the -136A allele than in those
      with the -136C allele. To investigate whether this difference in transcriptional
      activity caused a difference in EtOH elimination, previous data on blood EtOH
      changes after 0.4 g/kg body weight alcohol ingestion were analyzed. When analyzed
      based on aldehyde dehydrogenase-2 gene (ALDH2) (487)Glu/Lys genotype, the
      significantly lower level of EtOH at peak in subjects with -136C/A and -136A/A
      genotype compared with subjects with -136C/C genotype indicated that -136 bp was
      a suggestive locus for differences in EtOH oxidation. This effect was observed
      only in subjects with ALDH2 (487)Glu/Glu. These results suggested that the SNP at
      -136bp in the ADH4 promoter had an effect on transcriptional regulation, and that
      the higher activity of the -136A allele compared with the -136C allele caused a
      lower level of blood EtOH after alcohol ingestion; that is, individuals with the 
      136A allele may consume more EtOH and might have a higher risk for development of
      alcohol dependence than those without the -136A allele.

PMID- 19182439
TI  - Safety evaluation of Trikatu, a generic Ayurvedic medicine in Charles Foster
      rats.
AB  - Chemical characterization and acute and sub-acute toxicity study of Trikatu, a
      generic herbal formulation of Indian system of medicine, was carried out in
      Charles Foster (CF) rats for safety profiling. In acute toxicity experiment,
      Trikatu at 2,000 mg/kg body weight once orally was well tolerated by the
      experimental animals (both male and female) and no changes were observed in
      mortality, morbidity, gross pathology, gain in weight, vital organ weight,
      hematological (total white blood cells (WBC) and red blood cells (RBC) count),
      biochemical parameters such as serum creatinine, serum glutamate oxaloacetate
      transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum lipid
      profile and tissue biochemical parameters such as reduced glutathione and
      malonaldehyde content as oxidative stress markers. In sub-acute experiment,
      Trikatu was administered at 5, 50 and 300 mg/kg body weight once daily for 28
      days in female CF rats, and non-significant changes were found in most of the
      parameters studied such as acute experiment except significant increase in low
      density lipoprotein (LDL) cholesterol level at 50 and 300 mg/kg body weight,
      decrease in high density lipoprotein (HDL) cholesterol level at 300 mg/kg body
      weight, increase in SGPT activity at 50 mg/kg body weight and decrease in WBC
      count at 300 mg/kg body weight on 28(th) day post treatment.

PMID- 19182440
TI  - Suppressive effect of Siraitia grosvenorii extract on dicyclanil-promoted
      hepatocellular proliferative lesions in male mice.
AB  - Dicyclanil (DC) generates reactive oxygen species (ROS) due to Cyp1a1 induction,
      and DNA damage caused by oxidative stress is probably involved in
      hepatocarcinogenesis in mice. To clarify the modifying effect of the Siraitia
      grosvenorii extract (SGE), which has antioxidative properties, we employed a 2
      stage liver carcinogenesis model in partially hepatectomized male ICR mice. Mice
      maintained on diet containing DC at a concentration of 1,500 ppm for 9 weeks
      after a single intraperitoneal injection of diethylnitrosamine (DEN) at a dose of
      30 mg/kg and they were given water containing 2,500 ppm of SGE for 11 weeks
      including 2 weeks as pre-administration on DC. SGE inhibited the induction of
      gamma-glutamyltranspeptidase-positive hepatocytes, lipid peroxidation, and gene
      expression of Cyp1a1, all of which were caused by DC. To examine whether SGE
      indirectly inhibits Cyp1a1 expression induced by inhibition of aryl hydrocarbon
      receptor (Ahr)-mediated signal transduction caused by DC, mice with high
      (C57BL/6J mice) and low affinities (DBA/2J mice) to Ahr were given DC-containing
      diet and/or SGE-containing tap water for 2 weeks. Cyp1a1 gene expression was
      significantly lower in C57BL/6J mice administered DC + SGE than in C57BL/6J mice
      administered DC alone; there was no difference in the Cyp1a1 expression between
      DBA/2J mice administered DC + SGE and DC alone. These results suggest that SGE
      suppresses the induction of Cyp1a1, leading to inhibition of ROS generation and
      consequently inhibited hepatocarcinogenesis, probably due to suppression of Ahr
      activity.

PMID- 19182441
TI  - Mutagenicity of water-soluble ZnO nanoparticles in Ames test.
AB  - A mutagenicity test was conducted on water-soluble ZnO nanoparticles capped with
      tetramethylammonium hydroxide in a bacterial reverse mutation assay using
      Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537, and Escherichia
      coli strain WP2uvrA(-), with and without metabolic activation by S9 mix in the
      preincubation method. Mutagenicity was negative in all strains.

PMID- 19182442
TI  - Higher susceptibility of NOG mice to xenotransplanted tumors.
AB  - The purpose of tumorigenicity testing, as applied not only to cell substrates
      used for viral vaccine manufacture but also stem cells used for cell-based
      therapy, is to discriminate between cells that have the capacity to form tumors
      and cells that do not. Therefore, tumorigenicity testing is essential in
      assessing the safety of these biological materials. Recently developed NOD/Shi
      scid IL2Rg(null) (NOG) mice have been shown to be superior to NOD/Shi-scid (SCID)
      mice for xenotransplantation of both normal and cancerous cells. To select a
      suitable mouse strain as a xenogenic host for tumorigenicity testing, we compared
      the susceptibility of NOG (T, B, and NK cell-defective), SCID (T and B cell
      defective), and the traditionally used nude (T cell-defective) mice to tumor
      formation from xenotransplanted HeLa S3 cells. When 10(4) HeLa S3 cells were
      subcutaneously inoculated into the flanks of these mice, the tumor incidence on
      day 22 was 10/10 (100%) in NOG, 2/10 (20%) in SCID, and 0/10 (0%) in nude mice.
      The subcutaneous tumors formed reproducibly and semiquantitatively in a dose
      dependent manner. Unexpectedly, half of the NOG mice (5/10) that had been
      inoculated with a mere 10(1) HeLa S3 cells formed progressively growing
      subcutaneous tumors on day 78. We confirmed that the engrafted tumors originated
      from inoculated HeLa S3 cells by immunohistochemical staining with anti-HLA
      antibodies. These data suggest that NOG mice may be the best choice as a suitable
      strain for testing tumorigenicity.

PMID- 19182443
TI  - Effects of restricted feeding on blood parameters in pregnant rabbits.
AB  - The effects of restricted feeding (20 g/day from gestational day (GD) 6 to 28) on
      pregnancy outcome and blood parameters were examined in pregnant rabbits. As
      compared with the group which was allowed free access to diet throughout the
      gestational period (NT group), the group subjected to restricted feeding (R
      group) showed significantly lower values in many parameters such as total
      protein, albumin and triglyceride on GDs 22 and 28, reflecting low nutritive
      conditions. In addition, there were significant changes in blood coagulation
      related parameters, suggesting an imbalance between coagulation and anti
      coagulation factors. Moreover, abortions occurred in about half of the animals of
      the R group between GDs 23 and 27. When aborted rabbits were compared with those
      which could maintain pregnancy under restricted feeding, total protein, albumin,
      platelets and antithrombin III values and especially blood progesterone
      concentration were significantly lower in aborted rabbits on GD 22, prior to
      occurrence of abortion. These results suggested that abortions due to restricted
      feeding might be brought about by lower nutritive conditions, an imbalance of
      blood coagulation-related factors and lower blood progesterone concentrations.

PMID- 19182444
TI  - [Young pharmacological researchers develop the way to drug discovery based on
      interpretation of diseases and medicinal assessment: the way to create new drugs
      by fields interchange. Foreword].

PMID- 19182445
TI  - [Functional alteration of nervous system in renovascular hypertension].
AB  - The role of nitric oxide (NO)-containing nerves in adrenergic neurotransmission
      in hypertension was studied in mesenteric resistance arteries without endothelium
      in 2-kidney-1-clip renal hypertensive rats (2K-1C RHR) and sham-operated
      normotensive rats (Sham-R). Mesenteric vascular beds isolated from 2K-1C RHR and
      Sham-R were perfused with Krebs solution and changes in perfusion pressure were
      measured with a pressure transducer. Perfusion of a NO synthase inhibitor, N
      omega-nitro-L-arginine methyl ester (L-NAME), markedly augmented vasoconstrictor
      responses to periarterial nerve stimulation (PNS) without affecting
      vasoconstriction induced by exogenously injected noradrenaline. L-NAME
      significantly increased the neurogenic release of NA evoked by PNS in both 2K-1C
      RHR and Sham-R preparations. The facilitatory effect of L-NAME based on the
      inhibition of NO production in 2K-1C RHR was less than that in Sham-R. These
      results suggest that the function of NO-containing nerves, which presynaptically
      inhibit adrenergic neurotransmission, is decreased in the renovascular
      hypertensive model rat.

PMID- 19182446
TI  - [Role of heart-type fatty acid binding protein in the brain function].
AB  - Long-chain polyunsaturated fatty acids (LCPUFAs) are components of membrane
      phospholipids and they are abundant in the brain. LCPUFAs are supposed to be
      involved in several brain functions including emotion, learning and memory.
      However, the mechanisms of effects of LCPUFAs on brain functions at cellular and
      molecular levels remains unclear. Because LCPUFAs are insoluble in the
      intracellular compartment, specific transporters are required to deliver LCPUFAs
      for appropriate intracellular compartments. Fatty acid binding proteins (FABPs)
      are believed to play crucial roles as their cellular shuttles. Among various
      FABPs, heart-type fatty acid binding protein (H-FABP) is highly expressed in
      neurons of the mature brain and involved in arachidonic acid incorporation in the
      brain. Moreover, the association of H-FABP and dopamine D2L receptor has been
      documented by our studies. In this context, we here examined behavioral and
      molecular biological phenotype of H-FABP gene-ablated mice to clarify function of
      H-FABP in the higher brain functions.

PMID- 19182447
TI  - [Nicotinic acetylcholine receptors are possible therapeutic targets for
      schizophrenia].
AB  - The rate of smoking in patients with schizophrenia is higher than that in the
      general population. Nicotinic acetylcholine receptors (nAChR) are involved in the
      sensorimotor gating deficits in schizophrenia. We have revealed that nicotine
      ameliorates the disruption of the PPI, a model of sensorimotor gating, which is
      induced by apomorphine, a dopamine receptor agonist, but is not effective for the
      disruption of the PPI induced by phencyclidine, a glutamine NMDA receptor
      antagonist, in rats. Furthermore, the ameliorating effect of nicotine is
      antagonized by methyllycaconitine, a selective alpha7 nAChR antagonist. The
      effect of nocitine was also investigated in the stereotyped behavior induced by
      apomorphine, however, nicotine was found to have no significant effect.
      Considering these results, the ameliorating effect of the disruption of the PPI
      via alpha7 nAChR is therefore thought to be involved in dopaminergic systems. The
      dopaminergic systems involved in alpha7 nAChR may be different from the systems
      involved in stereotypy. In addition, this review describes the effects of the
      alpha7 nicotinic receptor agonists.

PMID- 19182448
TI  - [Protective effect of Morinda citrifolia on the ischemic neuronal damage].
AB  - The fruits juice of Morinda citrifolia (Noni juice) is a well known healthy drink
      and has various pharmacological effects such as antioxidant. Here, we focused on
      the protective effect of Okinawa Noni juice (ONJ) against ischemic stress using
      cerebral ischemia-reperfusion model mice. We found that free intake of 10% ONJ
      for 7 days showed the protective effect on neuronal damage after ischemic stress,
      while 3% ONJ did not show such effects. It has recently reported that glucose
      intolerance might be induced by ischemic stress and controlling of the blood
      glucose levels in the early phase of ischemic stress seems to be important for
      good prognosis. Interestingly, we have found the glucose intolerance was
      developed on 1st day after ischemic stress, while it disappeared on 3rd day. On
      the other hand, neuronal damage gradually developed from 1st to 5th day after
      ischemic stress. These results indicate that development of glucose intolerance
      might be one of the exacerbating factors of neuronal damage after ischemic
      stress. Noteworthy, the development of glucose intolerance on 1st day after
      ischemic stress significantly suppressed by ONJ in a dose-dependent manner. These
      results suggest that protective effect of ONJ might be mediated by suppression of
      ischemic stress-induced glucose intolerance.

PMID- 19182449
TI  - [From ethnic difference to ethnic similarity. Foreword].

PMID- 19182450
TI  - [History of the discussion on ethnic difference at ICH].
AB  - This paper describes the history of discussions on ethnic differences at the
      International Conference on Harmonization of technical requirements for
      registration of pharmaceuticals for human use (ICH). The first part of this paper
      gives a short outline of the purpose, organization, history, decision making
      process of the ICH. The ICH process consists of five steps. Step 1: Consensus
      building by Expert Working Group (EWG); Step 2: Confirmation of six-party
      consensus; Step 3: Regulatory consultation and discussion; Step 4: Adoption of an
      ICH harmonized tripartite guideline and Step 5: Implementation. Ethnic factors in
      the acceptability of foreign clinical data ("Ethnic Difference") was one of the
      14 topics on Efficacy. The author being one of the members of ICH-E5 EWG took
      part in the discussion of Ethnic Difference. The second part of this paper,
      describes the history of the discussion on this topic (from its inception to the
      finalization of the guideline) focusing on Step 2. A retrospective survey on
      individual pharmacokinetic data of around 80 drugs approved or under development
      in the 3 regions was conducted. In drafts 2 and 3, acceptance of phase 1 study
      only was discussed. But the proposal was opposed by industry members from US and
      EU. In drafts 4 and 5, the concept of "triage" was introduced and several
      algorithms were proposed, but finally a consensus could not be reached because
      the proposal was not so pragmatic. In drafts 7 and 8, the concept of "bridging
      study" was discussed to solve the problem of conducting phase II and III studies.
      Again, a consensus could not be reached. After the discussion of the "complete
      clinical data package" as proposed in drafts 9-12, the bridging study was once
      again discussed in drafts 13-19. Finally, draft 20 was confirmed and the
      discussion then moved to Step 3.

PMID- 19182451
TI  - [From ethnic difference to ethnic similarity].
AB  - It becomes the important issue for the medical supplies administration to solve
      the drug lag in our country. As means to overcome both the slow speed and high
      cost of clinical trial for new drug application in Japan, it seems useful to
      carry out clinical development simultaneously in East Asia countries such as
      China, Korea and Taiwan where it is thought that each country has similar
      ethnicity one another. When conducting simultaneous development with the same
      protocol in plural countries, it should be avoided that side effect develops
      abusively. In addition, both the effectiveness and safety expected after
      marketing should be secured in each country by a recommended amount of medicine
      for usage provided by simultaneous development between many countries. It is
      necessary for ethnic similarity to be shown so that development between the many
      countries in the same dosage is permitted at least. It is expected that the
      possibility of mutual utilization of clinical trial data of China, Korea and
      Japan will be shown by pharmacokinetics and pharmacodynamics examinations based
      on clinical test data of these countries by the Scientific Research funded by
      MHLW. On the other hand, it seems that it is meaningful and significant to
      examine the similarity at the gene level from various points of view. In order to
      give grounds for the validity of carrying out clinical trial in the same protocol
      in East Asia countries, it may be useful to examine genetic diversity of East
      Asia countries with plural heredity anthropological techniques such as heredity
      distance, and compare degree of the genetic diversity between the races of East
      Asia countries and that of other regions, for example, West Europe countries
      which have been recognized as one clinical trial field.

PMID- 19182452
TI  - [Pharmacogenomics: inter-ethnic and intra-ethnic differences in pharmacokinetic
      and pharmacodynamic profiles of clinically relevant drugs].
AB  - Intra- and inter-ethnic differences in pharmacokinetic and pharmacodynamic
      profiles of clinically relevant drugs are important issues not only for scenes of
      appropriate drug use in clinical settings but also for those of the drug
      development. Pharmacogenomics is extremely useful for understanding these racial
      differences. In this presentation, I will introduce pharmacogenomic concepts
      (e.g., single nucleotide polymorphisms (SNPs) and haplotype) for interpretation
      of racial differences in some drugs; pharmacogenomics of drug transporters such
      as OATP1B1 (organic anion transporting-polypeptide 1B1) and OCT1 (organic cation
      transporter 1) in pravastatin, metformin, and rosuvastatin will be discussed as
      model drugs.

PMID- 19182453
TI  - [Multi-national clinical trial in circulatory disorders].
AB  - As Japan becomes more integrated into the global market, pharmaceutical research
      and development (R&D) in Japan faces considerable challenges. While global
      simultaneous development including Asian countries has become a common strategy
      for multi-national pharmaceutical companies, Japan has been frequently set aside
      because of its provincial regulatory and clinical trial infrastructure.
      Meanwhile, many improvement programs in pharmaceutical area have been initiated
      in Japan. With this increased scrutiny, significant improvements in regulatory
      process, clinical trial costs, and site performance are anticipated over the next
      few years. RENAAL is the first multi-national clinical trial involving Japanese
      patients diabetic nephropathy associated with type II diabetes mellitus. In this
      article, issues which have been observed in the process of conducting multi
      national clinical trial were discussed based on the experience with RENAAL. It is
      hoped that, as we gain more experiences in multi-national clinical trials,
      solutions for these issues are found in near future.

PMID- 19182454
TI  - [Multinational clinical trial in Japan and Korea on detrusitol].
AB  - A randomized, double-blind, placebo- and active comparator-controlled study was
      conducted in 69 centers to compare detrusitol and oxybutynin with placebo in
      Japanese and Korean patients with an overactive bladder (OAB). Detrusitol had
      similar efficacy but was better tolerated than oxybutynin in Japanese and Korean
      patients with OAB. The study result was acknowledged as pivotal data in the
      clinical data package when NDA was filed and successfully approved both in Japan
      and Korea. Some differences were found in the efficacy and safety of the drug
      between the Japanese and Korean data, though. We therefore investigated the
      differences through stratified analysis; however exact causes could not be
      identified. This study is positioned as a first multinational clinical trial
      conducted in East Asia. From the aspects of utilization of interoperable data
      obtained from such multinational clinical trials for NDA filing and earliest
      possible registration of drugs in the participating countries, we believe it is
      important to accumulate more experiences in conducting multinational clinical
      trials. At this time, it is our prime task to minimize the "drug lag" in Japan; I
      think improving the speed of clinical trials is one of the factors to solve the
      issue. Global clinical trials involving Western and Asian countries make it
      possible to use the study data effectively and commonly in many countries.
      Moreover, from the viewpoint of revitalization of clinical trials, conducting
      global clinical trials is critically important; so we intend to continue
      accumulation of our experiences in global clinical trials.

PMID- 19182455
TI  - [Reasonable dispensing fee for patients].
AB  - The actual pharmacist workload is not always reflected in dispensing fees, while
      patients do not always understand the system of dispensing fees. In this study,
      the relation between the time required for dispensing and prescription details
      and that between the time required for instruction on drug administration and
      instruction details in nine pharmacies in Chiba prefecture were investigated. As
      a result of linear regression analysis, it was suggested that, compared with
      doses, the number of drug items more greatly affected the time required for
      dispensing. For oral drugs, the following relation was suggested in the study:
      [dispensing time (sec)]=29.3+27.5 x [number of items]+0.7 x[dosing days]+94.4 x
      [number of items]+7.1 x [dosing days]. Based on the actual dispensing fees
      claimed, fees per second of dispensing were estimated at 0.7 point. For drug
      administration instruction, it was considered reasonable to classify instructions
      into three categories according to the instruction details and set fees by the
      categories. When any further pharmaceutical expertise is required, fees should
      not be set according to the workload but additional fees should be provided to
      reward expertise.

PMID- 19182456
TI  - [Solid states fluorescence study of p-dimethylaminobenzonitrile by co-grinding
      with cyclodextrins].
AB  - The molecular status of a freeze-dried sample or a ground mixture of p
      dimethylaminobenzonitrile (DMABN) with alpha-, beta-, or gamma-cyclodextrins
      (CDs) was examined using solid-state fluorescence measurements. A twisted
      intramolecular charge transfer (TICT) emission of DMABN crystals was shown at 475
      nm. Emission peaks of freeze-dried samples were observed at 450, 380, and 393 nm
      in alpha-CD/DMABN, beta-CD/DMABN, and gamma-CD/DMABN systems, respectively. It
      was speculated that DMABN molecules existed as a twisted form in the cavity of
      alpha-CD, and as a plane structure in that of beta-CD or gamma-CD. On the other
      hand, fluorescence emission peaks of ground mixtures of DMABN with alpha-, beta-,
      or gamma-CD were observed at around 450 nm. When DMABN was ground together with
      microcrystalline cellulose, which cannot form an inclusion complex, only TICT
      emission was detected. These results suggest that the observed shift in the
      fluorescence peak could be due to inclusion phenomena. When the ground mixtures
      were crystallized under humid conditions, fluorescence emission peaks were
      observed at 450 nm in alpha-CD and of around 400 nm in beta- and gamma-CD
      systems. It is concluded that the conformation of the DMABN molecules in a
      crystalline CD/DMABN inclusion complex change depending on the size of the CD
      cavity.

PMID- 19182457
TI  - Clinical investigations in primary care.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that
      represents the most common form of dementia. The most prominent feature of AD is
      the decline in cognitive function, with an early impairment of episodic memory.
      The memory deficit of an AD patient is characterized by the amnestic syndrome of
      the medial temporal type. As the disease progresses, the condition often
      manifests in language disorders, visuospatial deficits and executive
      dysfunctions. Patients often have neuropsychiatric disturbances, as apathy and
      psychotic symptoms. Loss of autonomy follows cognitive impairment. The clinical
      diagnosis of AD is based on a complete medical examination with a
      neuropsychological evaluation. The FCSRT (free and cued selective reminding test)
      is recommended for the identification of the amnestic syndrome of the medial
      temporal type, which is defined by: (1) a very poor free recall and (2) a
      decreased total recall due to an insufficient effect of cueing. The
      neuropsychological tests should also assess other cognitive functions that may be
      perturbed in AD, such as executive functions, praxis, visuospatial capacities and
      language. Neuroimaging and biological exams (genetics, biomarkers) are of great
      utility in the evaluation. Other medical, neurological, or psychiatric disorders
      which could account for the impairment in memory and related symptoms must be
      always investigated.

PMID- 19182458
TI  - The concept of mild cognitive impairment: relevance and limits in clinical
      practice.
AB  - Subtle cognitive impairments without dementia are common in the elderly
      population and numerous nosological entities have been proposed for their
      classification. The concept of mild cognitive impairment has become increasingly
      popular both in clinical practice and in research. It has been developed to
      describe a transitional zone between the cognitive changes of normal aging and
      early Alzheimer's disease or other forms of dementia. Its interest lies mainly in
      early identification of individuals who might be at risk of developing rapid
      cognitive decline. But the further one tends towards the early detection, the
      greater is the risk to lose in specificity. A number of other factors such as
      depression, metabolic or nutritional disorders, medication use, may cause
      cognitive dysfunctions and are reversible. The concept of mild cognitive
      impairment arouses a debate about its heterogeneity,limits, and relevance in
      clinical practice and research.

PMID- 19182459
TI  - Pathological substrates of cognitive decline in Alzheimer's disease.
AB  - The progressive development of Alzheimer's disease (AD)-related lesions such as
      neurofibrillary tangles,amyloid deposits and synaptic loss within the cerebral
      cortex is a main event of brain aging.Recent neuropathologic studies strongly
      suggested that the clinical diagnosis of dementia depends more on the severity
      and topography of pathologic changes than on the presence of a qualitative
      marker. However, several methodological problems such as selection biases, case
      control design,density-based measures, and masking effects of concomitant
      pathologies should be taken into account when interpreting these data. In last
      years, the use of stereologic counting permitted to define reliably the cognitive
      impact of AD lesions in the human brain. Unlike fibrillar amyloid deposits that
      are poorly or not related to the dementia severity, the use of this method
      documented that total neurofibrillary tangles and neuron numbers in the CA1 field
      are the best correlates of cognitive deterioration in brain aging. Loss of
      dendritic spines in neocortical but not hippocampal areas has a modest but
      independent contribution to dementia. In contrast, the importance of early
      dendritic and axonal tau-related pathologic changes such as neuropil threads
      remains doubtful. Despite these progresses, neuronal pathology and synaptic loss
      in cases with pure AD pathology cannot explain more than 50% of clinical
      severity. The present review discusses the complex structure/function
      relationships in brain aging and AD within the theoretical framework of the
      functional neuropathology of brain aging.

PMID- 19182460
TI  - Functional imaging in mild cognitive impairment and early Alzheimer's disease: is
      it pertinent?
AB  - Neuroimaging techniques, namely positron emission tomography (PET), single photon
      emission computed tomography (SPECT), and magnetic resonance imaging (MRI) are
      increasingly used to study mild cognitive impairment (MCI) and its conversion to
      dementia, as well as early Alzheimer's disease (AD). Despite an important overlap
      of the various imaging parameter values between MCI,early AD and controls, some
      markers may help clinical diagnosis in individual patients. For example,the
      combination of significantly reduced hippocampal volume and brain hypometabolism
      in a MCI patient establishes the anatomical and functional features seen in
      dementia. In association with clinical information, the topographic localization
      of the hypometabolism will help to precise the type of dementia. Functional brain
      activation studies using functional MRI and PET are not used for clinical
      purpose, but they allow to determine the differences between control and
      pathological states and thus to characterize the functional abnormalities
      specific to the disease. Finally, the use of biomarkers of the neuropathological
      lesions constitutes the most promising tool to accurately diagnose MCI and early
      AD patients.

PMID- 19182461
TI  - Electrophysiological markers of rapid cognitive decline in mild cognitive
      impairment.
AB  - Electroencephalography (EEG) is an easily accessible and low-cost modality that
      might prove to be a particularly powerful tool for the identification of subtle
      functional changes preceding structural or metabolic deficits in progressive mild
      cognitive impairment (PMCI). Most previous contributions in this field assessed
      quantitative EEG differences between healthy controls, MCI and Alzheimer's
      disease(AD) cases leading to contradictory data. In terms of MCI conversion to
      AD, certain longitudinal studies proposed various quantitative EEG parameters for
      an a priori distinction between PMCI and stable MCI. However, cross-sectional
      comparisons revealed a substantial overlap in these parameters between MCI
      patients and elderly controls. Methodological differences including variable
      clinical definition of MCI cases and substantial interindividual differences
      within the MCI group could partly explain these discrepancies. Most importantly,
      EEG measurements without cognitive demand in both cross-sectional and
      longitudinal designs have demonstrated limited sensitivity and generally do not
      produce significant group differences in spectral EEG parameters. Since the
      evolution of AD is characterized by the progressive loss of functional
      connectivity within neocortical association areas, event-modulated EEG dynamic
      analysis which makes it possible to investigate the functional activation of
      neocortical circuits may represent a more sensitive method to identify early
      alterations of neuronal networks predictive of AD development among MCI cases.
      The present review summarizes clinically significant results of EEG activation
      studies in this field and discusses future perspectives of research aiming to
      reach an early and individual prediction of cognitive decline in healthy elderly
      controls.

PMID- 19182462
TI  - The future: new methods of imaging exploration in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex disease characterized by a whole cascade of
      pathological events. During the last 100 years, the role of amyloid in the
      development of AD has been the focus of major research. Today there is hope that
      amyloid imaging may help in the early detection of the disease and be used for
      evaluating new drug therapies including neuroprotective and preventive therapies
      in AD. The rapid development of the molecular imaging techniques now allows in
      vivo imaging not only of brain functional activity such as cerebral blood flow,
      cerebral glucose metabolism and neurotransmitter activity, and receptor density,
      but also pathological processes such as amyloid plaques and microglial activation
      in AD. Several positron emission tomography amyloid imaging ligands have recently
      been developed and tested in AD patients. High amyloid content can be detected in
      vivo by positron emission tomography in prodromal AD preceding the impairment of
      functional activity like cerebral glucose metabolism, and reduction in
      cholinergic activity, which are likely to follow the course of cognitive
      impairment.

PMID- 19182463
TI  - Pharmacological interventions in primary care: hopes and illusions.
AB  - Alzheimer's disease is a neurodegenerative disease characterized by senile
      plaques, neurofibrillary tangles, synaptic loss, neuronal death and cholinergic
      deficits, causing cognitive, behavioral and psychological deficits, as well as a
      functional impairment that results in serious caregiver distress and a great
      economic burden worldwide. High hopes rose with the development of symptomatic
      treatments,resulting from randomized controlled trials using cholinergic
      enhancers or cholinesterase inhibitors, such as donepezil, galantamine and
      rivastigmine. When memantine, an NMDA antagonist,was approved and the first phase
      III antiamyloid immunization was launched, many clinicians eagerly anticipated
      the first disease-modifying drugs in their daily practice. For the treatment of
      behavioral and psychological symptoms of dementia (BPSD), atypical antipsychotics
      and new-generation antidepressants also seemed to offer great promises, mainly
      because of their good tolerance and side effect profiles. Hopes, however, were
      followed by desillusions: subsequent studies demonstrated that cholinesterase
      inhibitors and memantine had only modest and short-lived effects on cognition and
      BPSD, and the effect of antipsychotics on BPSD appeared questionable. Disease
      modifying drugs such as antiamyloid immunization or amyloid clearance medication
      had to be abandoned for safety reasons or absence of efficacy. Although the early
      treatment of vascular risk factors is increasingly recognized in Alzheimer's
      disease prevention because of their implication in the amyloid cascade,
      randomized controlled trials have yielded largely negative results.
      Therefore,pharmacological as well as fundamental research that better underpins
      the complex pathophysiology of this devastating disease constitutes one of the
      biggest challenges of the 21st century.

PMID- 19182464
TI  - Investigations in primary care.
AB  - Vascular cognitive impairment relates to subjects who have a broad spectrum of
      cognitive deficits,including all forms of mild to severe cognitive impairment
      associated with and presumed to be caused by cerebrovascular diseases. The latter
      may be represented by multiple cortical infarcts, multiple subcortical infarcts,
      or both, silent infarcts, strategic infarcts, small-vessel disease with white
      matter lesions, and lacunes, all more or less related to stroke. Some authors
      also include in the category of vascular cognitive impairment Alzheimer's disease
      patients with evidence of additional vascular lesions. The recognition of early
      cognitive decline in the primary care setting is an important step as it may
      allow an early referral of patients to the specialist level, thus permitting a
      correct diagnosis of the etiologic subtype and the best treatment approach for
      that particular patient. The aim of this chapter is to provide an overview of the
      role of the primary care physician in the screening of patients with suspected
      vascular cognitive decline. Patients in whom screening for cognitive decline
      could be of clinical relevance are depicted, and a brief overview of
      investigations and diagnostic tests in the primary care setting is outlined. This
      specific diagnostic approach includes suggestions on how to take the clinical
      history, how to perform the physical examination, and on how to choose the
      appropriate tools for the cognitive and non-cognitive screening; finally, the
      role of neuroimaging in the primary care setting is illustrated.

PMID- 19182465
TI  - The concept of vascular cognitive impairment.
AB  - Vascular cognitive impairment (VCI) is the modern term related to vascular burden
      of the brain,reflecting all encompassing effects of cerebrovascular disease (CVD)
      on cognition. VCI include all levels of cognitive decline from mild deficits in
      one or more cognitive domains to a broad dementia-like syndrome. VCI incorporates
      the complex interactions between vascular risk factors, CVD etiologies and
      cellular changes within the brain and cognition. Vascular risk factors towards
      VCI include,e.g. arterial hypertension, high cholesterol, and diabetes. VCI
      includes the common poststroke dementia and vascular dementia (VaD). The main
      subtypes of VaD include the cortical VaD or multi-infarct dementia also referred
      as poststroke VaD and subcortical ischemic vascular disease and dementia or small
      vessel dementia. Traditional vascular risk factors and stroke are also
      independent factors for the clinical presentation of Alzheimer's disease. In
      addition to these vascular factors, CVD/strokes, infarcts and white matter
      lesions may trigger and modify progression of Alzheimer's disease.Whilst CVD is
      preventable and treatable, it clearly is a major factor in the prevalence of
      cognitive impairment in the elderly worldwide.

PMID- 19182466
TI  - Defining the neuropathological background of vascular and mixed dementia and
      comparison with magnetic resonance imaging findings.
AB  - The concept of vascular dementia (VaD) has greatly evolved in the past decades.
      Advances in neuroimaging techniques have led to a better identification of cases
      with small vessel disease and chronic ischemic changes. Autopsy data from
      population-based studies have revealed the frequent occurrence of both vascular
      and degenerative lesions in aged brains. However, the clinical significance of
      vascular pathology has been difficult to establish. This chapter will review data
      from clinicoradiological and clinicopathological studies that have attempted to
      define the cognitive impact of macroscopic and microscopic ischemic pathology in
      pure VaD and in cases with associated degenerative pathology. Magnetic resonance
      imaging studies have focused on lacunes and white matter lesions, whereas autopsy
      series have provide important insights into the clinical correlates of
      macroinfarcts,lacunes, diffuse and periventricular demyelination, microinfarcts
      and focal and diffuse gliosis.Results from these studies have led to a better
      understanding of the influence of lesion type,location and severity on cognitive
      function. Vascular scores have been proposed that can be combined with well
      established classifications of Alzheimer's disease (AD) pathology to distinguish
      mixed dementias from pure AD and pure VaD.

PMID- 19182467
TI  - Is it possible to treat vascular dementia?
AB  - Randomized controlled trials of primary and secondary prevention of vascular
      dementia demonstrate real effects on the cause or progression of disease (disease
      modifying treatment). These strategies lead to a reduction in all cerebrovascular
      risk factors, in particular hypertension. Such treatment may prevent dementia by
      reducing stroke and possibly by other mechanisms that remain undetermined,such as
      those involved in neurodegeneration and cell death. Curative treatment of
      vascular dementia, particularly given recent studies on cholinesterase inhibitors
      (rivastigmine, donepezil and galantamine) and memantine, is still ineffective.
      There is insufficient evidence to support widespread use of these drugs in
      vascular dementia. Particular considerations should be taken into account in
      clinical trials. Vascular dementia is a heterogeneous disease with different
      subtypes and mechanisms.Therefore, well-designed, adequately powered trials
      accounting for this heterogeneity, with better clinical definitions and an
      assessment and detection of cognitive and global changes specific to vascular
      dementia, are needed.

PMID- 19182468
TI  - Dementia with Lewy bodies: clinical diagnosis and therapeutic approach.
AB  - Dementia with Lewy bodies is one of the most common dementias in the elderly
      after Alzheimer's disease. It can be recognized on the basis of several clinical
      characteristics including progressive dementia with marked slowing and
      fluctuations, persistent visual hallucinations and an extrapyramidal syndrome.
      Several other clinical and imaging features are highly suggestive such as the
      presence of rapid eye movement sleep disorder, severe sensitivity to neuroleptics
      and specific neuroimaging abnormalities. Therapeutic strategies include
      prescription of L-dopa and cholinesterase inhibitors such as rivastigmine, and
      avoidance of anticholinergic medications and neuroleptics. Physicians who care
      for older people should have a heightened awareness of this entity in order to
      diagnose it early, avoid mistaking it for delirium and initiate appropriate
      treatment.

PMID- 19182469
TI  - Significance of brain lesions in Parkinson disease dementia and Lewy body
      dementia.
AB  - Dementia is increasingly recognized as a common feature in patients with
      Parkinson disease (PD)and dementia with Lewy bodies (DLB), both sharing many
      clinical and morphological features and believed to form a continuum within the
      spectrum of Lewy body diseases. Based on a large autopsy series of parkinsonism
      (31-37% with dementia) and review of the recent literature, the pathological
      changes underlying cognitive impairment in PD with dementia (PDD) and DLB are
      discussed. PD cases with Lewy body stages 3-5, i.e. only mild to moderate
      cortical alpha-synuclein (alphaSyn) depositions,and no additional pathologies,
      are rarely associated with cognitive impairment, which is frequently seen in PD
      and DLB cases with considerable cortical and limbic alphaSyn load (increasing
      Lewy body densities) and/or associated widespread Alzheimer-type pathology.
      Clinicopathological studies show a negative relation between cognitive impairment
      and both cortical Lewy body pathology and Alzheimer type changes, suggesting that
      these either alone or in combination are major causes of cognitive dysfunction,
      while others related them to presynaptic alphaSyn aggregates. The neuropathology
      of PDD and DLB is similar, without significant differences between cortical and
      subcortical Lewy bodies and the pattern of synuclein pathology in the brainstem,
      but there are topographic differences in nigral lesions, more frequent affection
      of the hippocampal CA 2/3 subareas and more severe diffuse amyloid plaque load in
      the striatum of DLB. In conclusion, the pathology underlying cognitive impairment
      in PDD and DLB is heterogeneous, but there are some differences in the topography
      and severity of lesions between both phenotypes that need further evaluation.

PMID- 19182470
TI  - Delineating dementia with lewy bodies: can magnetic resonance imaging help?
AB  - As future treatments increasingly target the protein chemistry underlying the
      different dementias, it becomes crucially important to distinguish between the
      dementias during life. Neither specific protein nor genetic markers are as yet
      available in clinical practice. However, neuroimaging is an obvious candidate
      technique that may yield enhanced diagnostic accuracy when applied to the
      dementias. The physiopathology and anatomopathology is complex in dementia with
      Lewy bodies (DLB). Besides the relative sparing of medial temporal lobe
      structures in DLB in comparison to Alzheimer's disease, no clear signature
      pattern of cerebral atrophy associated with DLB has been established so far.
      Among others, one reason may be the difficulty in visualizing the small brain
      nuclei that are differentially involved among the dementias. While we think that
      structural magnetic resonance imaging neuroimaging should be part of the
      diagnostic workup of most dementia syndromes due to its usefulness in the
      differential diagnosis, its contribution to a positive diagnosis of DLB is as yet
      limited. The development of different neuroimaging techniques may help
      distinguish reliably DLB from other neurodegenerative disorders. However, in
      order to become accepted as part of standard care, these techniques must still
      prove their effectiveness under routine conditions such as those encountered by
      the general practitioner.

PMID- 19182471
TI  - Pharmacotherapy of Parkinson disease dementia and Lewy body dementia.
AB  - The pharmacotherapy of Parkinson disease dementia and Lewy body dementia with
      cholinesterase inhibitors and selected psychotropic drugs is relatively new.
      Review of literature supplemented by expert opinion. Cholinesterase inhibitors
      can be used by primary care practitioners and specialists, with often clinically
      meaningful results. Primary care practitioners play an essential role in the
      diagnosis and management of patients with these conditions.

PMID- 19182472
TI  - Clinical features and diagnosis of frontotemporal dementia.
AB  - Frontotemporal degeneration (FTD), formerly known as Pick's disease has become
      recognized as a distinct and relatively common entity encompassing behavioural
      (bvFTD language (PPA) and extrapyramidal (CBD/PSP) presentations. Further
      clinical subdivisions such as semantic dementia(SD), and pathological subtypes
      such as mesial temporal sclerosis increase the complexity of diagnosis.The
      relatively younger age of onset, the typical presentations of syndromes and focal
      asymmetrical frontotemporal atrophy on imaging allows experienced clinicians to
      make the diagnosis confidently as long as the overlap between the syndromes is
      recognized. There is also an overlap with ALS pathologically and clinically. The
      underlying histology in FTD/Pick complex is ubiquitin positive tau and synuclein
      negative neuronal inclusions (FTLD-U) in more than half of autopsies and tau
      positive CBD/PSP/ Pick bodies (FTLD-T) in the rest. The clinical syndromes of
      bvFTD and SD are likely associated with FTLD-U and PPA/CBDS/PSP with FTLD-T, but
      there is too much overlap to predict the pathology from the clinical syndromes
      reliably. The ubiquitin-tau pathological dichotomy is best considered under the
      Pick complex umbrella to allow for the significant overlap. So far trazodone in
      behavior and galantamine in aphasia had symptomatic benefit in small trials and
      SSRI-sand antipsychotics in uncontrolled reports were used as symptomatic
      therapies. Recent discoveries of tau and progranulin (in the ubiquitin-positive
      cases) mutations on chromosome 17 and other mutations on chromosome 3 and 9 in
      the high incidence of autosomal dominant families and a common protein
      abnormality, the TDP-43 in FTLD-U and ALS are likely to be important in finding
      therapeutic targets.

PMID- 19182473
TI  - Neuropathological spectrum of frontal lobe dementias.
AB  - Frontotemporal dementia (FTD) is characterized by different severity of
      frontotemporal atrophy, and histologically by neuronal loss, gliosis and
      spongiosis. Due to the new discoveries in biochemistry,genetics and
      neuropathology, re-examination of the former neuropathological criteria was
      necessary.Actually, we distinguish subgroups on the basis of the presence or
      absence of intraneuronal or intraneuronal and glial inclusions: the so-called FTD
      tauopathies, such as Pick's disease, corticobasal degeneration, progressive
      supranuclear palsy, FTD with parkinsonism linked to chromosome 17,argyrophilic
      grain disease and neurofibrillary tangle dementia. FTD nontauopathies include
      dementia lacking distinctive histology (without any known inclusion) and FTD
      (clinically with or without motor neuron disease) with ubiquitin-immunoreactive
      inclusions. In the latter group, a new pathological protein, the TAR-binding
      protein (TDP-43), was recently described as the main component of inclusion, and
      several new mutations were also discovered. The new neuropathological criteria
      could be a great help in the neuropathological diagnosis and in further
      clinicopathological studies, and the new discoveries are useful in understanding
      the underlying disease processes.

PMID- 19182474
TI  - Frontotemporal dementia neuroimaging: a guide for clinicians.
AB  - Frontotemporal dementia represents an important cause of dementia that requires
      differentiation from Alzheimer's disease. As molecular therapies for both
      diseases begin to emerge, neuroimaging biomarkers will be needed that can improve
      diagnostic accuracy and enable treatment monitoring.At present, structural
      magnetic resonance imaging provides a useful adjunct to clinical
      assessment,helping to distinguish frontotemporal dementia from Alzheimer's
      disease and from nonneurodegenerative disease. Future imaging research will seek
      to more directly assay disease by assessing network level pathophysiology and
      accumulation of misfolded proteins in cerebral tissues.

PMID- 19182475
TI  - Frontotemporal dementia: therapeutic interventions.
AB  - The management of frontotemporal dementia (FTD), a disorder characterized by
      varied behavioral symptoms, primarily involves the use of psychoactive
      medications. Although there are no approved treatments for the disorder,
      selective serontonin receptor inhibitors, such as sertraline, paroxetine, or
      fluoxetine, can decrease disinhibition-impulsivity, repetitive behaviors, and
      eating disorders in FTD. Low doses of trazodone or an atypical antipsychotic such
      as aripriprazole can also help manage significantly disturbed or agitated
      behavior. The acetylcholinesterase inhibitors used for patients with Alzheimer's
      disease have not had significant efficacy for patients with FTD, but memantine,
      another dementia medication, is under investigation for the treatment of this
      disorder. In addition to drug therapy, the nonpharmacological management of
      patients with FTD focuses on education, behavioral interventions, and care of the
      caregivers. Most recently, investigators have initiated steps toward rational
      drug therapy with the development of outcome measures for clinical drug trials in
      FTD and the characterization of treatment targets such tau protein or the TAR DNA
      binding protein 43. This approach holds great promise for an eventual treatment
      for this devastating early-onset dementia.

PMID- 19182476
TI  - Nursing students' self-reported knowledge of genetics and genetic education.
AB  - INTRODUCTION: Nurses need to use genetic information in care; several areas of
      current need include primary care, public health, cardiovascular, geriatric and
      oncology nursing. Nursing faculties may be reluctant to add genetics to existing
      courses, let alone tackle the work of teaching an entire course in genetics.
      OBJECTIVES: The purpose of this study was to describe the current genetic
      knowledge of nursing students regarding genetics and genetic education. METHODS:
      This is a self-administered cross-sectional survey. A total of 162 of 209 nursing
      students returned a questionnaire. Data from the surveys reflect the students'
      self-reported knowledge regarding medical genetics (response rate = 77.5%).
      RESULTS: The majority of students noted 'some' to 'minimal' knowledge of
      Mendelian inheritance and human chromosome abnormalities. In terms of awareness
      of genetic abnormalities and disorders, students claimed to have 'high' knowledge
      of breast cancer, phenylketonuria, thalassemia, colon cancer, Rh factor, cleft
      lip/palate, hemophilia, color blindness, and polydactyly. Students stated that
      they would like to receive more education related to genetic diseases and genetic
      counseling (93.9%). CONCLUSIONS: The majority of students reported very little
      knowledge of genetics and genetic disorders. Most of students responded
      positively to all the education methods suggested in the questionnaire, adding
      that they would like more education about genetics. The results from this study
      may help to reform and upgrade the educational strategy concerning genetics in
      the Schools of Health.

PMID- 19182477
TI  - Reducing the global genomic inequity gap: development of an african genome
      project.

PMID- 19182478
TI  - Cutaneous venous malformations in familial cerebral cavernomatosis caused by
      KRIT1 gene mutations.
AB  - BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular lesions
      characterized by abnormally enlarged capillary cavities without intervening brain
      parenchyma. Although often asymptomatic, seizures, cerebral haemorrhages and
      focal neurological deficits are well-documented complications. Mutations in the
      CCM1 (7q21-22), CCM2 (7p13-15) and CCM3 (3q25.2-27) genes have been identified in
      familial CCM. In rare instances, the association of congenital hyperkeratotic
      cutaneous capillary-venous malformations (HCCVMs) with CCM1 has been reported.
      OBSERVATIONS: We studied 6 members of a family with CCMs. Four members of the
      family developed late-onset multiple, tiny, bluish, soft, cutaneous papules,
      mainly located on the face, arm and abdominal area, corresponding histologically
      to venous malformations. A splice donor site mutation in intron 4 (c. 1146 + 1 G-
      >A) in the CCM1 gene was identified. CONCLUSIONS: Our findings suggest that
      mutations in the KRIT1 gene may cause phenotypically heterogeneous cutaneous
      vascular lesions other than those previously described as HCCVMs.

PMID- 19182479
TI  - Changes in cortical activation during retrieval of clock time representations in
      patients with mild cognitive impairment and early Alzheimer's disease.
AB  - OBJECTIVE: We investigated healthy controls (HCs), and patients with mild
      cognitive impairment (MCI) and early Alzheimer's disease (AD) to identify
      neuronal correlates of clock time representation and changes resulting from
      neurodegenerative processes using functional magnetic resonance imaging. METHODS:
      Two clock-specific tasks demanding conceptual knowledge of clock hands, i.e. a
      minute hand and an hour hand task, were compared with a semantic control task.
      RESULTS: We observed that the minute hand task provoked a stronger activation of
      areas in the parietal lobes known to be involved in spatial mental imagery, while
      the semantic task primarily activated regions of the superior temporal lobes
      associated with verbal conceptual knowledge. The performance of the MCI group did
      not differ from that of the HC group, but additional activation was found in
      several brain regions. Decreased activation was detected during the minute hand
      task in the right middle temporal gyrus. Patients with early AD showed
      deteriorated performance in both clock tasks along with reduced activation in the
      occipital lobes and the left fusiform gyrus. Additional activation was detected
      in the precuneus. CONCLUSIONS: The fusiform gyrus might be crucial for the visual
      semantic retrieval of clock time representation. In patients with early AD,
      access to this visual-semantic knowledge appears to be reduced.

PMID- 19182480
TI  - Frontal assessment battery and brain perfusion imaging in early dementia.
AB  - BACKGROUND/AIMS: The frontal assessment battery (FAB) is reported to be a useful
      tool for screening frontal function. However, the neural substrates involved
      remain to be elucidated. The aim of the present study was to identify the brain
      regions responsible for FAB performance in patients with early dementia. We
      sought a correlation between FAB scores and brain perfusion. METHODS: A total of
      117 subjects participated in this study (Alzheimer's disease = 51, frontotemporal
      dementia = 14, vascular dementia = 13, dementia with Lewy bodies = 7, psychiatric
      disease = 7, mild cognitive impairment = 11, controls = 14). They underwent brain
      single photon emission computed tomography with (99m)Tc-ethylcisteinate dimer,
      and we analyzed the data, using a regional cerebral blood flow (rCBF)
      quantification software program, 3DSRT (3-dimensional stereotaxic region of
      interest template). RESULTS: FAB scores had a moderately positive correlation
      with left callosomarginal and precentral rCBF. Comparison of rCBF between high-
      and low-scoring FAB groups revealed that the latter showed significantly lower
      rCBF in the bilateral callosomarginal and left precentral regions. CONCLUSION:
      The results in this study suggest that the FAB mainly reflects the function of
      the callosomarginal and precentral segments, especially the left side, and that
      it might be a valid frontal lobe function test.

PMID- 19182481
TI  - Risk factors for falls in community-dwelling patients with Alzheimer's disease
      and dementia with Lewy bodies: walking with visuocognitive impairment may cause a
      fall.
AB  - BACKGROUND/AIMS: To identify risk factors for falls in community-dwelling
      patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB).
      PATIENTS: 78 consecutive patients (51 AD, 27 DLB) were recruited from the Niigata
      Rehabilitation Hospital memory clinic. METHODS: We assessed the number of falls
      each patient had had in the previous 4 months. The data for DLB patients without
      motor parkinsonism were analyzed both as part of the whole DLB group and
      separately to determine the effect of parkinsonism alone on falls. RESULTS: Of 78
      patients, 17 (21.8%) reported at least 1 fall during the period. A diagnosis of
      DLB, visual hallucinations, parkinsonism and cognitive fluctuation were
      significant predictors, but none of them was significant in the stepwise
      multivariate analysis. After excluding patients with parkinsonism, the use of
      hypnotics-anxiolytics and a worse score on the constructional task were
      significant and independent predictors of falling. CONCLUSION: Parkinsonism was a
      major risk factor for falls. When AD or DLB patients walk with incongruent visual
      information, they may increase their postural sway or instability, because of
      their executive dysfunction. If elementary and/or higher-order visuocognitive
      impairment in AD or DLB patients alters visual information sufficiently, they may
      fall when walking.

PMID- 19182483
TI  - Effect of oxcarbazepine in the treatment of agitation and aggression in severe
      dementia.
AB  - BACKGROUND/AIMS: To evaluate the efficacy of oxcarbazepine (OXC) in the treatment
      of agitation and aggression in patients with Alzheimer's disease, vascular
      dementia or both. METHODS: This is an 8-week, multicenter, randomized, double
      blind, placebo-controlled trial carried out independently of the pharmaceutical
      industry. Changes in the agitation and aggression subscore of the
      Neuropsychiatric Inventory (NPI) were the primary outcomes. The secondary out-
      comes were the changes in the caregivers' total burden scores (measured by the
      NPI) and changes in the Brief Agitation Rating Scale (BARS). RESULTS: In total,
      103 institutionalized patients at 35 sites were randomized to the trial. After 8
      weeks, no statistically significant differences were found between the 2 groups
      for all outcomes. A trend was observed in favor of the OXC group in the reduction
      in the scores on the BARS (p = 0.07). CONCLUSION: This study found no significant
      effect of OXC in treatment of agitation and aggression in patients with dementia.

PMID- 19182482
TI  - Education attenuates the association between dietary patterns and cognition.
AB  - BACKGROUND/AIMS: Various foods have been shown to be associated with cognitive
      outcomes. As individual food items are not consumed in isolation, we examined the
      association between dietary patterns and cognitive function, with special
      attention to the role of education in this association. METHODS: Analyses were
      carried out on 4,693 stroke-free white European participants of the Whitehall II
      study. Two dietary patterns were determined using principal component analysis: a
      'whole food' and a 'processed food' pattern. Cognitive function was assessed
      using a battery of 5 tests. RESULTS: After adjustment for demographic, behavioral
      and health measures, higher intake of 'whole food' diet was associated with lower
      and high consumption of 'processed food' with higher odds of cognitive deficit.
      However, adjustment for education significantly attenuated most of these
      associations. CONCLUSIONS: Education, through its role as a powerful confounder,
      shapes the relationship between dietary patterns and cognitive deficit in a
      healthy middle-aged UK cohort.

PMID- 19182484
TI  - Multisubstance use as a feature of addiction to anabolic-androgenic steroids.
AB  - The aim of this study was to explore and describe total drug use among anabolic
      androgenic steroid (AAS) users and the reasons given for the use of these drugs.
      The study was based on semi-structured interviews and questionnaires involving 32
      patients who were attending an addiction centre in Orebro, Sweden, for AAS use.
      The results indicated that a history of polysubstance use among the patients was
      frequent. Over half were using drugs of abuse and also taking various other
      pharmaceuticals. Almost half of the patients took human growth hormones, and
      almost half of the interviewed persons were drinking alcohol to a hazardous or
      harmful extent. The most common reason given for taking AAS and other hormones
      was to increase muscle mass and strength, but some participants also used insulin
      as a means of losing fat. Cannabis was used to improve sleep, heroin to decrease
      pain and amphetamine to increase endurance and burn fat. Our data suggest that
      most of the current AAS users who have been admitted to a treatment programme are
      multiple drug users with polysubstance dependence. The study stresses the
      importance of carefully examining total drug use as part of the assessment
      regimen for this group.

PMID- 19182485
TI  - A literature review of international implementation of opioid substitution
      treatment in prisons: equivalence of care?
AB  - BACKGROUND/AIMS: Opioid substitution treatment (OST) is an effective treatment
      for heroin dependence. The World Health Organization has recommended that OST be
      implemented in prisons because of its role in reducing drug injection and
      associated problems such as HIV transmission. The aim of this paper was to
      examine the extent to which OST has been implemented in prisons internationally.
      METHODS: Literature review. RESULTS: As of January 2008, OST had been implemented
      in prisons in at least 29 countries or territories. For 20 of those countries,
      the proportion of all prisoners in OST could be calculated, with results ranging
      from less than 1% to over 14%. At least 37 countries offer OST in community
      settings, but not prisons. CONCLUSION: This study has identified an increase in
      the international implementation of OST in prisons. However, there remain large
      numbers of prisoners who are unable to access OST, even in countries that provide
      such programs. This raises issues of equivalence of care for prisoners and HIV
      prevention in prisons.

PMID- 19182486
TI  - Friedreich's ataxia: a new mutation in two compound heterozygous siblings with
      unusual clinical onset.

PMID- 19182487
TI  - The ophthalmoscope: Helmholtz's Augenspiegel.
AB  - The origins of Helmholtz's invention of the ophthalmoscope are found in the
      ancient observation that the back of the eye appeared black. In 1703, Jean Mery
      reported that the luminosity of the cat's eye could be seen when the animal was
      held under water, and Mariotte observed that a dog's eye was luminous but
      erroneously thought this was because its choroid was white. Prevost made a
      breakthrough when he deduced it was incident light and not light coming out of
      the eye. Purkinje and von Brucke used lenses to attempt to see the fundus and
      almost succeeded. However, it was Helmholtz who created the first useable
      ophthalmoscope, whose development and clinical application are traced in this
      paper. One of the greatest physical scientists in many spheres of learning, his
      biography is briefly sketched.

PMID- 19182488
TI  - Richard Bright and his neurological studies.
AB  - Richard Bright was one of the famous triumvirate of Guy's Hospital physicians in
      the Victorian era. Remembered for his account of glomerulonephritis (Bright's
      disease) he also made many important and original contributions to medicine and
      neurology. These included his work on cortical epileptogenesis, descriptions of
      simple partial (Jacksonian) seizures, infantile convulsions, and a variety of
      nervous diseases. Most notable were his reports of neurological studies including
      papers on traumatic tetanus, syringomyelia, arteries of the brain, contractures
      of spinal origin, tumours of the base of the brain, and narcolepsy. His career
      and these contributions are outlined.

PMID- 19182489
TI  - Narcolepsy.

PMID- 19182490
TI  - 67-kDa laminin receptor in human bile duct carcinoma.
AB  - BACKGROUND/AIM: Abnormal interaction of epithelial cells with laminin component
      of basement membrane may account for altered biological behavior of cells,
      influencing proliferation, adhesion, and motility. In the current study, we
      investigated the role of 67-kDa laminin receptor (67LR), a high affinity receptor
      for laminin, in aggressiveness of bile duct carcinoma. METHODS: Fifty-two
      paraffin-embedded specimens and 22 fresh tissues of patients with bile duct
      carcinoma were analyzed using immunohistologic and real-time polymerase chain
      reaction techniques, respectively. Expression of 67LR on the bile duct carcinoma
      QBC939 cells was examined by flow cytometry. The effects of 67LR on the adhesive
      and invasive abilities of QBC939 cells were determined by adhesion and invasion
      assay in vitro. RESULTS: Both at the mRNA and protein level, bile duct carcinoma
      cells expressed a higher level of 67LR than normal epithelial cells (p < 0.01).
      The expression of 67LR was correlated inversely with differentiation extent of
      tumor (p < 0.05). The 67LR level was significantly increased in patients with
      lymph node metastases than in patients without lymph node involvement (p < 0.01).
      Flow cytometry showed that 69.9 +/- 1.1% of QBC939 cells expressed 67LR.
      Expression of 67LR increased the adhesion and invasion of QBC939 cells. 60 and
      120 min of incubation of 67LR antibodies, MLuC5, induced 46.3 +/- 2.2 and 61.3 +/
      2.1% inhibition of adhesion, respectively. The invasive ability of QBC939 cells
      to Matrigel was also reduced by 67LR antibodies, MLuC5. CONCLUSIONS:
      Overexpressing 67LR on bile duct carcinoma was associated with invasion and
      metastasis of bile duct carcinoma. Blockage of 67LR suppressed adhesion and
      invasion of bile duct carcinoma.

PMID- 19182491
TI  - Blood pressure in renal transplant recipients: are there independent predictors
      for achieving target blood pressure?
AB  - BACKGROUND: Post-transplant hypertension is a major modifiable risk factor for
      graft and patient survival. The aim of this study was to establish independent
      predictors for achieving systolic, diastolic and overall blood pressure target
      [Kidney Disease Outcome Quality Initiative (K/DOQI) target blood pressure <130/80
      mm Hg] in renal-transplant recipients (RTRs) and to consider whether current
      management strategies are adequate to achieve this aim. METHODS: The most recent
      office blood pressure readings were collected for 513 RTRs at least 6 months
      after transplantation. In addition, demographic data, comorbidities, medications
      prescribed, weight, duration of transplantation, and laboratory parameters were
      recorded. Logistic regression analysis was used to determine whether any
      covariables were significant (p < 0.05) independent predictors of controlled
      blood pressure (<130/80 mm Hg). RESULTS: Approximately 50% of the RTRs had blood
      pressures <130/80. There was a marked terminal digit preference demonstrated.
      Subjects who were female, had diabetes, did not have heart disease or had a lower
      albumin:creatinine ratio had a higher probability to achieve good blood pressure
      control. Diabetics were more likely to be prescribed 3 or more antihypertensive
      agents. CONCLUSIONS: This study shows that improvements in blood pressure control
      can be achieved. People with diabetes were 2.1 times more likely to meet target
      blood pressure. Further improvements in blood pressure control may require
      different treatment strategies in addition to the current pharmacological
      approach.

PMID- 19182492
TI  - Thrombospondin in renal disease.
AB  - Thrombospondins (TSPs) are multifunctional matricellular glycoproteins which are
      involved in the regulation of angiogenesis, proliferation, apoptosis, the NO-cGMP
      dependent protein kinase pathway and transforming growth factor (TGF) beta
      activation. The TSP family consists of 5 members, but currently only data on
      effects of TSP-1 and TSP-2 in renal disease are available. Both TSPs are hardly
      expressed within the healthy renal cortex and can be upregulated during renal
      disease. Using different animal models for renal disease, TSP-1 and -2 were found
      to be important regulators of pathophysiological changes during renal disease
      with similar and contrary effects. TSP-1 is a major activator for TGF-beta
      resulting in profibrotic effects in the injured kidney. In contrast, TSP-2 lacks
      the ability for its activation. Proapoptotic actions of TSP-1 were found during
      renal ischemia/reperfusion injury. While TSP-1 exerts proinflammatory actions,
      the currently available data for TSP-2 propose anti-inflammatory effects for this
      molecule. Both TSPs are known angiogenesis inhibitors, which could be proved for
      TSP-2, but antiangiogenic effects for TSP-1 were only evident by treatment with
      TSP-1 peptides in renal disease. In addition, TSP-2 can inhibit cell
      proliferation and matrix metalloproteinase 2 activity.

PMID- 19182493
TI  - Cerebellar fastigial nuclear inputs and peripheral feeding signals converge on
      neurons in the dorsomedial hypothalamic nucleus.
AB  - Previous studies have indicated that neurons in the dorsomedial hypothalamic
      nucleus (DMN) receive feeding-related signals from the gastric vagal nerves,
      glycemia as well as leptin. On the other hand, it is intriguing that the
      cerebellum participates in regulating nonsomatic visceral activities including
      food intake via the direct cerebellohypothalamic projections. The present study
      was designed to examine, by using extracellular recordings in vivo in rats,
      whether the cerebellar fastigial nucleus (FN) could reach and converge with the
      feeding-associated gastric vagal, glycemia and leptin signals onto single DMN
      neurons. Of the 200 DMN neurons recorded, 104 (52%) responded to the cerebellar
      FN stimulation, in which 95 (91.3%) were also responsive to the gastric vagal
      stimulation, suggesting a convergence of cerebellar FN and gastric vagal inputs
      on the DMN neurons. Moreover, a summation of responses was observed (n = 10) when
      the cerebellar FN and gastric vagal nerve were simultaneously stimulated. Among
      the 18 DMN neurons receiving convergent inputs from the cerebellar FN and gastric
      vagal nerves, 16 (88.9%) cells also responded to the systemic administrations of
      glucose and leptin. These results demonstrated that the cerebellar FN-afferent
      inputs, together with the feeding signals from the gastric vagal nerves, blood
      glucose as well as leptin, converge onto single DMN neurons, suggesting that a
      somatic-visceral integration related to the feeding may occur in the DMN and the
      cerebellum may actively participate in the feeding regulation through the
      cerebellar FN-DMN projections.

PMID- 19182494
TI  - Three-dimensional ultrasound of ophthalmic pathologies.
AB  - PURPOSE: To assess three-dimensional echography image quality and multiplanar
      imaging for the visualization of vitreoretinal and choroidal diseases. METHODS:
      In an observational cross-sectional study, 20 eyes of 20 patients presenting
      different vitreoretinal and choroidal pathologies have been evaluated with three
      dimensional ultrasonography (3DUS). RESULTS: Of the 20 eyes, an epiretinal
      membrane was present in 2 eyes, diabetic macular edema in 6, a macular hole in 2,
      a myopic posterior detachment in 2, myopic peripapillary detachment of the
      pigment epithelium in 1, choroidal melanoma in 4, optic nerve glioma in 1 case,
      carotidocavernous fistula in 1 and an intravitreal dislocation of an intraocular
      lens in 1 eye. 3DUS was effective in wide-field representation of the
      vitreoretinal interface during macular edema, in good-quality visualization of
      the dislocated intraocular lens and in calculating the volume of choroidal
      melanoma. No advantages were found in other evaluated cases if compared with the
      already existing imaging techniques. CONCLUSIONS: One of the main advantages of
      3DUS was the possibility to obtain a wide-field representation of spatial
      relationships between the lesions and the surrounding ocular structures.

PMID- 19182495
TI  - Different expression of vascular endothelial growth factor and pigment epithelium
      derived factor between diabetic and non-diabetic epiretinal membranes.
AB  - PURPOSE: To determine whether there is a difference in protein levels of
      expression of vascular endothelial growth factor (VEGF), pigment epithelium
      derived factor (PEDF), platelet-derived growth factor (PDGF) and transforming
      growth factor beta(1) (TGF-beta(1)) between diabetic and non-diabetic epiretinal
      membranes (ERMs). METHODS: ERMs and vitreous were surgically removed from the
      eyes of 8 patients with proliferative diabetic retinopathy and from 6 patients
      with proliferative vitreoretinopathy. Concentrations of VEGF, PEDF, PDGF and TGF
      beta(1) were investigated by an enzyme-linked immunosorbent assay. RESULTS: The
      concentrations of VEGF were higher in ERMs from patients with diabetes (9.2 +/-
      8.0 pg/microg protein) compared to those without diabetes (1.2 +/- 3.0 pg/microg
      protein; p = 0.026), while the concentrations of PEDF were higher in ERMs from
      patients without diabetes (7.5 +/- 1.5 ng/microg protein) compared to those with
      diabetes (3.5 +/- 1.5 ng/microg protein; p = 0.002). In addition, the VEGF-to
      PEDF ratio was higher in diabetic ERMs (2.80 +/- 1.83) than in non-diabetic ones
      (0.17 +/- 0.09; p = 0.019). However, the concentrations of PDGF and TGF-beta(1)
      in membranes were not different between patients with diabetes and those without
      diabetes. CONCLUSION: This study found the difference in protein levels of
      expression of VEGF and PEDF between diabetic and non-diabetic ERMs. These results
      suggest that a disturbance in the balance between angiogenic and anti-angiogenic
      factors may play an important role in angiogenesis in diabetic ERMs.

PMID- 19182497
TI  - The CT evaluation of neoarytenoid soft tissue after an arytenoidectomy during a
      supracricoid partial laryngectomy.
AB  - OBJECTIVE: To evaluate the postoperative laryngeal CT findings of neoarytenoid
      soft tissue at an arytenoidectomy site during a supracricoid partial
      laryngectomy, and to compare its thickness to the mucosa over the spared
      arytenoid cartilage. MATERIALS AND METHODS: Thirty-one patients underwent a
      supracricoid partial laryngectomy with (n = 14) or without (n = 17) an
      arytenoidectomy. A postoperative laryngeal CT examination was performed to
      statistically compare the thickness of the neoarytenoid soft tissue to the mucosa
      over the spared arytenoids. RESULTS: The neoarytenoid soft tissue revealed an
      eccentric prominence in all 14 arytenoidectomy sites. Further, the neoarytenoid
      soft tissue was consistently thicker than the mucosa over spared arytenoids
      cartilage (p < 0.01), however did not exceed 11 mm. CONCLUSION: The eccentric
      prominence of neoarytenoid soft tissue at the arytenoidectomy site during a
      supracricoid partial laryngectomy should be identified and distinguished from a
      recurrent mass when compared to spared arytenoid cartilage on a postoperative
      laryngeal CT.

PMID- 19182496
TI  - The clinical usefulness of (18)F-FDG PET/CT for the evaluation of lymph node
      metastasis in periorbital malignancies.
AB  - OBJECTIVE: The aim of this study was to assess the clinical role of (18)F-FDG
      PET/CT for the evaluation of lymph node metastasis in periorbital malignancies,
      compared with CT alone. MATERIALS AND METHODS: We analyzed eighteen PET/CT and CT
      scans in 15 patients with biopsy-proven periorbital malignancies. We compared the
      diagnostic capabilities of PET/CT and CT with regard to nodal metastasis by level
      by-level analysis and by N staging prediction. The reference standards were
      surgical pathology (n = 7) from dissected lymph node specimens and the results
      from radiological follow-up (n = 11, mean 20.5 months; range 10-52 months).
      Moreover, any changes in patient care as prompted by PET/CT were recorded and
      compared with treatment planning for CT alone. RESULTS: PET/CT had a sensitivity
      of 100%, while CT had a sensitivity of 57% (p = 0.03) for nodal metastasis by
      level-by-level analysis. PET/CT had a specificity of 97%, positive predictive
      value of 93%, negative predictive value of 100%, and diagnostic accuracy of 98%,
      while the CT values for these same parameters were 97%, 89%, 82%, and 84%,
      respectively. PET/CT correctly predicted N staging with an accuracy of 100%,
      while CT was only 83% accurate (p = 0.01). Regarding the impact on patient care,
      the extent of surgery for regional lymph nodes and the treatment decision were
      modified by PET/CT in 39% of patients. CONCLUSION: PET/CT could provide useful
      information in the management of regional lymph node metastases in patients with
      periorbital malignancies.

PMID- 19182498
TI  - Malignant pure pulmonary ground-glass opacity nodules: prognostic implications.
AB  - OBJECTIVE: This study was designed to evaluate follow-up results in terms of
      patient prognosis for malignant pulmonary nodules depicted as pure ground-glass
      opacity (GGO) lesion observed at high-resolution CT (HRCT). MATERIALS AND
      METHODS: Surgical removal for malignant GGO nodules was accomplished in 58
      patients (26 men, 32 women; mean age, 57 years; age range, 29-78 years). Patient
      prognoses were assessed by patient clinical status and the presence of changes in
      nodule size determined after a follow-up HRCT examination. Differences in patient
      prognoses were compared for nodule number, size, surgical method, change in size
      before surgical removal, and histopathological diagnosis by use of Fisher's exact
      test and Pearson's chi-squared test. RESULTS: Of the 58 patients, 40 patients
      (69%) were confirmed to have a bronchioloalveolar carcinoma (BAC) and 18 patients
      (31%) were confirmed to have an adenocarcinoma with a predominant BAC component.
      Irrespective of nodule size, number, treatment method, change in size before
      surgical removal and histopathological diagnosis, neither local recurrence nor a
      metastasis occurred in any of these patients as determined at a follow-up period
      of 24 months (range; 12-65 months). Of 14 patients with multiple GGO nodules, all
      of the nodules were resected without recurrence in six patients. In the remaining
      eight patients, the remaining nodules showed no change in size in seven cases and
      a decrease in size in one case as determined after a follow-up CT examination.
      CONCLUSION: Prognoses in patients with pure GGO malignant pulmonary nodules are
      excellent, and not significantly different in terms of nodule number, size,
      surgical method, presence of size change before surgical removal and
      histopathological diagnosis.

PMID- 19182499
TI  - "Crazy-paving" patterns on high-resolution CT scans in patients with pulmonary
      complications after hematopoietic stem cell transplantation.
AB  - OBJECTIVE: To describe the pulmonary complications following hematopoietic stem
      cell transplantation (HSCT) that can present with a "crazy-paving" pattern in
      high-resolution CT scans. MATERIALS AND METHODS: Retrospective review of medical
      records from 2,537 patients who underwent HSCT. The "crazy-paving" pattern
      consists of interlobular and intralobular septal thickening superimposed on an
      area of ground-glass attenuation on high-resolution CT scans. The CT scans were
      retrospectively reviewed by two radiologists, who reached final decisions by
      consensus. RESULTS: We identified 10 cases (2.02%), seven male and three female,
      with pulmonary complications following HSCT that presented with the "crazy
      paving" pattern. Seven (70%) patients had infectious pneumonia (adenovirus,
      herpes simplex, influenza virus, cytomegalovirus, respiratory syncytial virus,
      and toxoplasmosis), and three patients presented with non-infectious
      complications (idiopathic pneumonia syndrome and acute pulmonary edema). The
      "crazy-paving" pattern was bilateral in all cases, with diffuse distribution in
      nine patients (90%), predominantly in the middle and inferior lung regions in
      seven patients (70%), and involving the anterior and posterior regions of the
      lungs in nine patients (90%). CONCLUSION: The "crazy-paving" pattern is rare in
      HSCT recipients with pulmonary complications and is associated with infectious
      complications more commonly than non-infectious conditions.

PMID- 19182500
TI  - Efficacy of barium-based fecal tagging for CT colonography: a comparison between
      the use of high and low density barium suspensions in a Korean population - a
      preliminary study.
AB  - OBJECTIVE: This preliminarily study was designed to determine and to compare the
      efficacy of two commercially available barium-based fecal tagging agents for CT
      colonography (CTC) (high-density [40% w/v] and low-density [4.6% w/v] barium
      suspensions) in a population in Korea. MATERIALS AND METHODS: In a population
      with an identified with an average-risk for colorectal cancer, 15 adults were
      administered three doses of 20 ml 40% w/v barium for fecal tagging (group I) and
      15 adults were administered three doses of 200 ml 4.6% w/v barium (group II) for
      fecal tagging. Excluding five patients in group I and one patient in group II
      that left the study, ten patients in group I and 14 patients in group II were
      finally included in the analysis. Two experienced readers evaluated the CTC
      images in consensus regarding the degree of tagging of stool pieces 6 mm or
      larger. Stool pieces were confirmed with the use of standardized CTC criteria or
      the absence of matched lesions as seen on colonoscopy. The rates of complete
      fecal tagging were analyzed on a per-lesion and a per-segment basis and were
      compared between the patients in the two groups. RESULTS: Per-lesion rates of
      complete fecal tagging were 52% (22 of 42; 95% CI, 37.7-66.6%) in group I and 78%
      (28 of 36; 95% CI, 61.7-88.5%) in group II. The difference between the two groups
      did not reach statistical significance (p = 0.285). The per-segment rates of
      complete tagging were 33% (6 of 18; 95% CI, 16.1%-56.4%) in group I and 60% (9 of
      15; 95% CI, 35.7%-80.3%) in group II; again, the difference between the two
      groups did not reach statistical significance (p = 0.171). CONCLUSION: Barium
      based fecal tagging using both the 40% w/v and the 4.6% w/v barium suspensions
      showed moderate tagging efficacy. The preliminary comparison did not demonstrate
      a statistically significant difference in the tagging efficacy between the use of
      the two tagging agents, despite the tendency toward better tagging with the use
      of the 4.6% w/v barium suspension.

PMID- 19182501
TI  - Percutaneous radiofrequency ablation for the hepatocellular carcinoma abutting
      the diaphragm: assessment of safety and therapeutic efficacy.
AB  - OBJECTIVE: To assess the safety and therapeutic efficacy of a percutaneous
      radiofrequency (RF) ablation for the hepatocellular carcinoma (HCC) abutting the
      diaphragm. MATERIALS AND METHODS: We retrospectively assessed 80 patients who
      underwent a percutaneous RF ablation for a single nodular (< 4 cm) HCC over the
      last four years. Each patient underwent an ultrasound-guided RF ablation using
      internally cooled electrodes for the first-line treatment. We divided patients
      into two subgroups based on whether the index tumor was abutting (less than 5 mm)
      the diaphragm or not: group A (abutting; n = 31) versus group B (non-abutting; n
      = 49). We compared the two subgroups for complications and therapeutic efficacy
      using image and the review of medical records. The statistical assessment
      included an independent t-test, Fisher's exact test, and chi-square test.
      RESULTS: The assessment of the diaphragmatic swelling at CT immediately following
      the procedure was more severe in group A than group B (mean thickness change:1.44
      vs. 0.46 mm, p = 0.00). Further, right shoulder pain was more common in group A
      than B (p = 0.01). Although minor complications (hemothorax 1 case, pleural
      effusion 1 case) were noted only in group A, no major thoracic complication
      occurred in either group. The technical success rate was lower in group A than
      group B (84% vs. 98%, p = 0.03). As well, the primary and secondary technique
      effectiveness rates in group A and group B were 90% versus 98% (p = 0.29) and 79%
      versus 91% (p = 0.25), respectively. The local tumor progression rate was higher
      in group A than in group B (29% vs. 6%, p = 0.02). CONCLUSION: We found that the
      percutaneous RF ablation for the HCC abutting the diaphragm is a safe procedure
      without major complications. However, it is less effective with regard to
      technical success and local tumor control.

PMID- 19182502
TI  - Does artificial ascites induce the heat-sink phenomenon during percutaneous
      radiofrequency ablation of the hepatic subcapsular area?: an in vivo experimental
      study using a rabbit model.
AB  - OBJECTIVE: To evaluate the effect of the heat-sink phenomenon induced by
      artificial ascites on the size of the ablation zone during percutaneous
      radiofrequency (RF) ablation of the hepatic subcapsular area in an in vivo rabbit
      model. MATERIALS AND METHODS: A total of 21 percutaneous rabbit liver RF
      ablations were performed with and without artificial ascites (5% dextrose aqueous
      solution). The rabbits were divided into three groups: a) control group (C, n =
      7); b) room temperature ascites group (R, n = 7); and c) warmed ascites group (W,
      n = 7). The tip of a 1 cm, internally cooled electrode was placed on the
      subcapsular region of the hepatic dome via ultrasound guidance, and ablation was
      continued for 6 min. Changes in temperature of the ascites were monitored during
      the ablation. The size of the ablation zones of the excised livers and immediate
      complications rates were compared statistically between the groups (Mann-Whitney
      U test, Kruskal-Wallis test, linear-by-linear association, p = 0.05). RESULTS:
      One rabbit from the "W" group expired during the procedure. In all groups, the
      ascites temperatures approached their respective body temperatures as the
      ablations continued; however, a significant difference in ascites temperature was
      found between groups "W" and "R" throughout the procedures (39.2+/-0.4 degrees C
      in group W and 33.4+/-4.3 degrees C in group R at 6 min, p = 0.003). No
      significant difference was found between the size of the ablation zones (782.4+/
      237.3 mL in group C, 1,172.0+/-468.9 mL in group R, and 1,030.6+/-665.1 mL in
      group W, p = 0.170) for the excised liver specimens. Diaphragmatic injury was
      identified in three of seven cases (42.9%) upon visual inspection of group "C"
      rabbits (p = 0.030). CONCLUSION: Artificial ascites are not likely to cause a
      significant heat-sink phenomenon in the percutaneous RF ablation of the hepatic
      subcapsular region.

PMID- 19182503
TI  - Slot-scan digital radiography of the lower extremities: a comparison to computed
      radiography with respect to image quality and radiation dose.
AB  - OBJECTIVE: To compare the slot-scan digital radiography (SSDR) of the lower
      extremity region and the computed radiography (CR) method with respect to the
      image quality and radiation exposure. MATERIALS AND METHODS: We enrolled 54
      patients who underwent both the SSDR and CR of the lower extremities. The study
      evaluated and statistically compared the image quality of four features (outer
      cortex, inner cortex, trabeculae and intermuscular fat) at six different levels
      (pelvis, hip, femur, knee, tibia and ankle) between each method. The image
      quality was evaluated using a visibility scale, and the entrance skin dose was
      measured using a dosimeter at three different levels of a phantom (hip, knee, and
      ankle). RESULTS: The mean image visibility scale values for the SSDR method were
      significantly higher than for the CR method. The entrance skin dose for the SSDR
      method was 278 microGy at each level, compared to the entrance skin doses of the
      CR method, which were 3,410 microGy for the hip, 1,152 microGy for the knee, and
      580 microGy for the ankle. CONCLUSION: Both the image quality and patient
      entrance skin dose data suggest that the SSDR method is superior to the CR method
      for the lower extremity musculoskeletal examination.

PMID- 19182504
TI  - Induction of upregulation and downregulation of the T-cell activation marker CD98
      in patients undergoing contrast-enhanced CT with iodinated non-ionic dimeric
      contrast medium.
AB  - OBJECTIVE: This study was designed to determine prospectively the expression of
      the multifunctional CD98 protein in peripheral white blood cells in patients
      receiving iodinated contrast media (CM) for a computed tomography (CT)
      examination. MATERIALS AND METHODS: In 12 adult patients that received non-ionic
      dimeric CM (iosimenol or iodixanol), the expression of CD98 was analyzed from
      samples of peripheral white blood cells obtained prior to, one hour, and 24 hours
      after CM injection by the use of flow cytometry analysis and the use of the
      direct immunofluorescence technique. RESULTS: Overall, expression of CD98 was
      significantly downregulated 24 hours after CM injection (51.9%+/-10.8% vs.
      38.8%+/-16.9%; p < 0.04). Patients that received iosimenol exhibited a more
      pronounced but not significant decrease of CD98 expression both one hour and 24
      hours after CM injection. In an analysis of specific patient responses, CD98
      downregulation occurred in eight patients. In two patients, CD98 was upregulated,
      and in the remaining two patients, expression remained unchanged. No patient
      acquired an adverse CM reaction. CONCLUSION: This is the first demonstration that
      CM may be a regulator of CD98 expression. To determine if upregulation is
      associated with an increased risk for the acquisition of an adverse CM-induced
      hypersensitivity reaction and if downregulation is associated without a risk for
      the acquisition of an adverse CM-induced hypersensitivity reaction, further
      studies with a larger population of patients are required.

PMID- 19182505
TI  - Gastrointestinal tract perforation: MDCT findings according to the perforation
      sites.
AB  - Our objective is to describe the characteristic CT findings of gastrointestinal
      (GI) tract perforations at various levels of the gastrointestinal system. It is
      beneficial to localize the perforation site as well as to diagnose the presence
      of bowel perforation for planning the correct surgery. CT has been established as
      the most valuable imaging technique for identifying the presence, site and cause
      of the GI tract perforation. The amount and location of extraluminal free air
      usually differ among various perforation sites. Further, CT findings such as
      discontinuity of the bowel wall and concentrated free air bubbles in close
      proximity to the bowel wall can help predict the perforation site. Multidetector
      CT with the multiplanar reformation images has improved the accuracy of CT for
      predicting the perforation sites.

PMID- 19182506
TI  - Imaging features of adult choledochal cysts: a pictorial review.
AB  - Choledochal cysts are rare congenital anomalies which are principally diagnosed
      by disproportional dilatation of the extrahepatic bile ducts. In addition,
      choledochal cysts are believed to arise from the anomalous union of the common
      bile duct and pancreatic duct outside the duodenal wall which is also proximal to
      the sphincter of the Oddi mechanism. The various types of choledochal cysts have
      been classified on the basis of these anomalous unions (Komi classification) and
      their anatomical locations (Todani classification). The multidetector computed
      tomography with reformatted imaging, magnetic resonance cholangiopancreatography,
      and an endoscopic retrograde cholangiography represent the important techniques
      providing the anatomical resolution and detail required to properly diagnose and
      classify choledochal cysts and their associated abnormal features of the biliary
      tree, as well as their pancreaticobile duct union. This study describes the
      various imaging features of a choledochal cyst in adults according to the various
      types of anomalous unions of the pancreaticobile duct according to Komi's
      classification and anatomic location according to Todani's classification.
      Lastly, we also review and discuss the associated abnormal findings developed in
      biliary systems.

PMID- 19182507
TI  - Four cases of a cerebral air embolism complicating a percutaneous transthoracic
      needle biopsy.
AB  - A percutaneous transthoracic needle biopsy is a common procedure in the practice
      of pulmonology. An air embolism is a rare but potentially fatal complication of a
      percutaneous transthoracic needle biopsy. We report four cases of a cerebral air
      embolism that developed after a percutaneous transthoracic needle biopsy. Early
      diagnosis and the rapid application of hyperbaric oxygen therapy is the mainstay
      of therapy for an embolism. Prevention is the best course and it is essential
      that possible risk factors be avoided.

PMID- 19182508
TI  - Fibroblastic type osteosarcoma of the ulna: a case report of a tumor in a rare
      location with atypical imaging findings.
AB  - The ulna is a rare site of origin for osteosarcoma, and purely osteolytic
      osteosarcomas are uncommonly noted on conventional radiographs. We present a
      patient with a lytic lesion of the distal ulna for which imaging findings
      suggested an aneurysmal bone cyst. The lesion was histologically confirmed to be
      a fibroblastic osteosarcoma.

PMID- 19182509
TI  - Adventitial cystic disease of the femoral vein: a case report with the CT
      venography.
AB  - Fewer than 20 cases of adventitial cystic disease of the vein have been reported
      in the worldwide literature. This small number of reported cases may be due not
      only to the disease's low incidence, but also to the difficulty in making the
      proper diagnosis. Many techniques have been used to investigate this disease, but
      venography has been the traditional diagnostic tool. In this report we present a
      case of adventitial cystic disease that was well demonstrated by CT venography.

PMID- 19182510
TI  - An unusual radiologic pattern of cryptogenic organizing pneumonia: diffuse
      pulmonary nodules in a leukemia patient.
AB  - The radiological appearance of diffuse discrete pulmonary nodules associated with
      cryptogenic organizing pneumonia (COP) has been rarely described. We describe a
      case of COP in 49-year-old woman with acute myeloid leukemia who developed
      diffuse pulmonary nodules during the second course of induction chemotherapy. The
      clinical status of the patient and imaging findings suggested the presence of a
      pulmonary metastasis or infectious disease. A video-assisted thoracoscopic lung
      biopsy resulted in the unexpected diagnosis of COP as an isolated entity. Steroid
      therapy led to dramatic improvement of the clinical symptoms and the pulmonary
      lesions.

PMID- 19182511
TI  - Renal and splenic micro-infarctions following bronchial artery embolization with
      tris-acryl microspheres.
AB  - A bronchial artery embolization (BAE) is an important therapeutic method used to
      control acute and chronic hemoptysis. We report a case of multiple micro-infarcts
      involving both the kidneys and spleen, following a BAE with 500-700 microm
      crossed-linked tris-acryl microspheres (Embospheres) in a patient with bronchial
      artery pulmonary vein shunts. The superior penetration characteristics of the
      microspheres may have resulted in the greater tendency to cross the bronchial
      artery pulmonary vein shunts, which subsequently caused the systemic infarcts in
      our patient. We propose the use of larger sized microspheres (700-900 microm),
      which may aid in avoiding this complication.

PMID- 19182512
TI  - Chemotherapeutic sensitization by endoplasmic reticulum stress: increasing the
      efficacy of taxane against prostate cancer.
AB  - Taxanes are first line drugs for treating prostate cancer recurrence after the
      failure of anti-androgen therapy. There is a need to make taxanes more effective
      since they only provide palliative benefit. Exploiting endoplasmic reticulum (ER)
      stress death signaling to enhance drug efficacy has not been delineated. Human PC
      3 cells were used as a model of hormone refractory prostate cancer. Thapsigargin
      and methylseleninic acid (MSA) were examined as sensitizers. Thapsigargin is a
      classic ER stress inducer. The activity of MSA in inducing ER stress has recently
      been studied by our group. The efficacy of single drug and the various
      combinations was evaluated by measuring apoptosis with a cell death ELISA kit.
      Thapsigargin increased the cell killing potency of paclitaxel or docetaxel by 10-
      to 12-fold, while MSA caused a 5- to 8-fold increase. Since thapsigargin is not
      used clinically because of its toxicity, the follow-up experiments were done with
      MSA. To test the hypothesis that a threshold level of ER stress is crucial to
      chemotherapeutic sensitization, three different approaches designed to dampen the
      severity of ER stress induced by MSA were examined. Lowering ER stress
      consistently attenuated the efficacy of MSA/taxane. GADD153 is a pro-apoptotic
      transcription factor which is upregulated during ER stress. Knocking down GADD153
      by siRNA also reduced the cell killing effect of MSA/taxane. Both the intrinsic
      and extrinsic apoptotic pathways were involved in the sensitization mechanism.
      Our study supports the idea that marshalling ER stress apoptotic response is
      conducive to chemotherapeutic sensitization.

PMID- 19182513
TI  - Putting HIV-1 apoptosis mediators to work against cancer: a killer job, with
      benefits.

PMID- 19182514
TI  - Silent beginning: early silencing of the MED1/MBD4 gene in colorectal
      tumorigenesis.

PMID- 19182515
TI  - Paths of FGFR-driven tumorigenesis.
AB  - Fibroblast growth factor receptors (FGFRs) comprise a subfamily of receptor
      tyrosine kinases (RTKs) that are master regulators of a broad spectrum of
      cellular and developmental processes, including apoptosis, proliferation,
      migration and angiogenesis. Due to their broad impact, FGFRs and other RTKs are
      highly regulated and normally only basally active. Deregulation of FGFR signaling
      by activating mutations or ligand/receptor overexpression could allow these
      receptors to become constitutively active, leading to cancer development,
      including both hematopoietic and solid tumors, such as breast, bladder and
      prostate carcinomas. In this review, we focus on potential modes of FGFR-mediated
      tumorigenesis, in particular, the role of FGFR1 during prostate cancer
      progression.

PMID- 19182516
TI  - Phase specific functions of the transcription factor TFII-I during cell cycle.
AB  - The post-embryonic cells, in a non-proliferating quiescent state (G(0)), require
      mitogenic signaling to drive them into cell cycle entry (G(1)). However, cell
      cycle events become largely independent of external signaling once cells begin
      DNA synthesis in S phase. Given these two phases of cell cycle are
      mechanistically distinct, it is unclear whether there could be coordinated
      transcriptional regulation between these phases. The signal induced
      multifunctional transcription factor TFII-I, upon growth factor signaling,
      undergoes tyrosine phosphorylation, which is essential for its transcriptional
      activation function and corresponding G(0)-G(1) transition. Here we show that
      silencing of TFII-I has unexpected defects in S-phase. The TFII-I KD cells
      exhibit significant delay entering into and executing S-phase progression and
      entry into G(2)/M phase but do not exhibit any significant mitotic defects as
      evidenced by post-mitotic G(1) entry and frequency of binucleation. Microarray
      analysis, coupled with functional validation, reveals cyclin D1 and PKC-beta as
      major downstream targets of TFII-I. Cyclin D1 is induced in G(1) and is necessary
      for G(1)/S transition. PKC-beta also activates cyclin D1 via NFkappaB. These
      observations suggest a transcriptional network during early phases of cell cycle
      mediated by TFII-I. Finally, we show that Cdk1 phosphorylates TFII-I at the
      G(2)/M boundary, which likely leads to its displacement from the condensed
      chromatin during prophase to pro-metaphase transition. Taken together, TFII-I
      appears to have distinct roles in distinct phases of the mammalian cell cycle.

PMID- 19182517
TI  - The homeotic protein HOXC13 is a member of human DNA replication complexes.
AB  - The homeotic (and oncogenic) HOXC13 protein was shown to have an affinity for a
      DNA fragment corresponding to the sequence covered by the pre-replicative complex
      of the human lamin B2 replication origin. We show here that HOXC13 is a member of
      human replicative complexes. Our fluorescent fusion-protein data demonstrate that
      it co-localizes with replication foci of early-S cells and that this peculiar
      behaviour is driven by the homeodomain. By ChIP analysis we also show that HOXC13
      binds the lamin B2 replication origin and the origins located near the TOP1 and
      MCM4 genes in asynchronously growing cells, whereas it does not bind these
      origins in G(0) resting cells, consistently with its involvement in origin
      function.

PMID- 19182519
TI  - Origin of carcinoma associated fibroblasts.
AB  - Recent evidence on the genomic integrity of non-malignant cells surrounding
      carcinoma cells has reinvigorated the discussion about the origin of the altered
      phenotype exhibited by carcinoma associated fibroblasts. Many hypotheses have
      been proposed for the origin of these altered cells, including standard
      connective tissue acute phase and stress response, fibroblast senescence,
      reciprocal interactions with the cancer cells, fibroblast specific somatic
      mutations, differentiation precursors and infiltrating mesenchymal stem cells.
      Here we review the definition of CAF phenotype and the evidence for each of those
      hypotheses, in the context of our current understanding of cancer etiology.

PMID- 19182518
TI  - Balancing the decision of cell proliferation and cell fate.
AB  - The control of cellular proliferation is key in the proper development of a
      complex organism, the maintenance of tissue homeostasis and the ability to
      respond to various hormonal and other inducers. Key in the control of
      proliferation is the retinoblastoma (Rb) protein which regulates the activity of
      a family of transcription factors known as E2Fs. The E2F proteins are now
      recognized to regulate the expression of a large number of genes associated with
      cell proliferation including genes encoding DNA replication as well as mitotic
      activities. What has also become clear over the past several years is the
      intimate relationship between the control of cell proliferation and the control
      of cell fate, particularly the activation of apoptotic pathways. Central in this
      connection is the Rb/E2F pathway that not only provides the primary signals for
      proliferation but at the same time, connects with the p53-dependent apoptotic
      pathway. This review addresses this inter-connection and the molecular mechanisms
      that control the decision between proliferation and cell death.

PMID- 19182520
TI  - Double duty of Atg9 self-association in autophagosome biogenesis.
AB  - The understanding of the membrane flow process during autophagosome formation is
      essential to illuminate the role of autophagy under various disease-causing
      conditions. Atg9 is the only identified integral membrane protein required for
      autophagosome formation, and it is thought to cycle between the membrane sources
      and the phagophore assembly site (PAS). Thus, Atg9 may play an important role as
      a membrane carrier. We report the self-interaction of Atg9 and generate an Atg9
      mutant that is defective in this interaction. This mutation results in abnormal
      autophagy, due to altered phagophore formation as well as inefficient membrane
      delivery to the PAS. Based on our analyses, we discuss a model suggesting dual
      functions for the Atg9 complex: by reversibly binding to another Atg9 molecule,
      Atg9 can both promote lipid transport from the membrane origins to the PAS, and
      also help assemble an intact phagophore membrane.

PMID- 19182521
TI  - A putative function of the nucleolus in the assembly or maturation of specialized
      messenger ribonucleoprotein complexes.
AB  - The nucleolus is a nuclear subcompartment with a well-defined function in
      ribosomal RNA transcription and assembly of ribosomal subunits. However, the
      nucleolus is multifunctional and involved in processes as diverse as regulation
      of mitosis, cell proliferation and viral infection. There is increasing evidence
      that, in addition to ribosomes, several different ribonucleoprotein (RNP)
      particles assemble or mature in the nucleolus, including the signal recognition
      particle (SRP) or viral RNPs. Here we discuss recent findings from mammalian and
      yeast cells that specific localized mRNAs or proteins that associate with
      localized mRNAs can accumulate in the nucleolus under particular conditions.
      Experimental evidence derived from studies on the nucleolar accumulation of yeast
      ASH1 mRNA and of cytoplasmic retention of its binding protein She2 are integrated
      into a hypothetical model that suggests a novel role of the nucleolus in the
      assembly of specific mRNPs.

PMID- 19182523
TI  - Piecemeal microautophagy of the nucleus: genetic and morphological traits.
AB  - Nucleus-vacuole (NV) junctions are formed in Saccharomyces cerevisiae through
      interactions between Vac8 in the vacuole membrane and Nvj1 in the perinuclear ER.
      Upon starvation, vesicles containing part of the nucleus emanate from these
      contact sites and finally pinch off into invaginations of the vacuole. Due to its
      morphological similarity to microautophagy this process had been termed
      "piecemeal microautophagy of the nucleus" (PMN). We recently discovered that a
      number of ATG genes required for macroautophagy and micropexophagy are also
      required for PMN and accordingly named it micronucleophagy. Therefore, PMN
      represents a novel model system to investigate the functions of the highly
      conserved but poorly understood core autophagic apparatus. We here extend the
      morphological analysis of PMN using immunogold and freeze fracture electron
      microscopy.

PMID- 19182522
TI  - The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal
      transition and cancer metastasis.
AB  - MicroRNAs (miRNAs) play essential roles in many physiological and pathological
      processes, including tumor development, by regulating the expression of a
      plethora of mRNAs. Although the importance of miRNAs in tumorigenesis is well
      established, only recently have reports elucidated miRNAs as promoters or
      suppressors of metastasis. The miR-200 family has been shown to inhibit the
      initiating step of metastasis, epithelial-mesenchymal transition (EMT), by
      maintaining the epithelial phenotype through direct targeting of transcriptional
      repressors of E-cadherin, ZEB1 and ZEB2. These findings shed light into a miRNA
      mediated regulatory pathway that influences EMT in a developmentally and
      pathologically relevant setting.

PMID- 19182524
TI  - miRNA, siRNA, piRNA: Knowns of the unknown.
AB  - RNA silencing is a common term for a group of mechanistically related pathways
      that produce and employ short non-coding RNA molecules to achieve sequence
      specific gene regulation. The RNase III-enzyme Dicer produces small RNAs (smRNAs)
      in both microRNA (miRNA) and RNA interference (RNAi) pathways. miRNAs modulate
      physiological and developmental gene expression. They are genome-encoded,
      endogenous negative regulators of translation and mRNA stability originating from
      long primary transcripts with local hairpin structures. RNAi is triggered by the
      processing of long double-stranded RNA (dsRNA) into small interfering RNAs
      (siRNAs), which mediate sequence-specific cleavage of nascent mRNAs. The third
      common class of repressive small RNAs, PIWI-associated RNAs (piRNAs), is produced
      in a Dicer-independent manner. Current data suggest that piRNAs protect the
      germline from mobile genome invaders such as transposons. A small RNA involved in
      RNA silencing associates with proteins in an effector ribonucleoprotein complex
      usually referred to as RNA-Induced Silencing Complex (RISC). Key components of
      RISC complexes are proteins of the Argonaute family, which determine RISC
      functions. During three days in May 2008, around two hundred scientists working
      on RNA silencing met at IMBA, Vienna for the 3(rd) Microsymposium on Small RNAs
      (Fig. 1) (www.imba.oeaw.ac.at/microsymposium) organized by Javier Martinez.

PMID- 19182525
TI  - Phylogenetic conservation of the preapoptotic calreticulin exposure pathway from
      yeast to mammals.
AB  - The pre-apoptotic exposure of calreticulin (CRT) on the cell surface determines
      the efficient engulfment of mouse or human tumor cells by antigen-presenting
      dendritic cells. CRT exposure is rapidly induced by anthracyclins and ionizing
      irradiation and follows a complex signal transduction pathway that is interrupted
      by depletion of PERK, caspase-8, BAP31, Bax, Bak or SNAREs, as well as by knock
      in mutation of eIF2alpha (to make it non-phosphorylable by PERK) or BAP31 (to
      render it uncleavable by caspase-8). Here, we show that yeast (Saccharomyces
      cerevisiae) can expose the CRT orthologue CNE1 on the surface in response to cell
      death induced by the anthracylin mitoxantrone (MTX). This MTX-triggered CNE1
      translocation is abolished by knockout of the yeast orthologues of PERK (Gcn2),
      BAP31 (Yet3) and SNAREs (Nyv1, Sso1). Altogether, our data point to the existence
      of an ancestral and cell death-related CRT exposure pathway with conserved
      elements shared between unicellular fungi and mammals.

PMID- 19182526
TI  - T cell dependence on mTOR signaling.
AB  - The mammalian target of rapamycin (mTOR) signaling pathway integrates signals
      from the environment to the nucleus for the regulation of cellular growth,
      metabolism and survival. Lymphocytes frequently rely on this pathway, but it is
      carefully regulated through the reception of signals via cytokine, growth factor
      and co-stimulatory receptors. Recent studies have begun to elucidate why T cell
      subsets rely on this pathway to varying degrees. Ultimately these findings will
      help distinguish the parameters that guide T cell homeostasis and activation
      induced function between the different T cell populations. The mTOR pathway has
      been the focus of many immunosuppressive and cancer treatment regimens, therefore
      there is a great need to understand the impact of suppression not only on the T
      cell populations targeted, but on bystander T cells as well.

PMID- 19182527
TI  - Evaluation of mTOR function by a gain-of-function approach.
AB  - The mammalian target of rapamycin (mTOR), a member of the phosphoinositide 3
      kinase related kinase (PIKK) family, plays a central role in the regulation of
      cell growth. The cellular function of mTOR has been proposed based solely on loss
      of-function analyses using the specific inhibitor rapamycin or RNAi-mediated
      knockdown. There have been recent reports of mTOR mutants with enhanced activity
      that were isolated by genetic screening in yeast. These isolated mTOR mutants
      exhibited enhanced kinase activity in vitro, and when expressed in cells,
      prevented the dephosphorylation of known mTOR substrates. The application of
      these mutants in gain-of-function analyses has enabled a re-evaluation of the
      function of mTOR. Although these studies confirmed many of the proposed mTOR
      functions some unexpected observations urged a reconsideration of the regulatory
      mechanisms and the physiological function of the mTOR pathway. Hyperactive mTOR
      mutants are thus valuable tools for analysis of the activation mechanism as well
      as the in vivo function of mTOR.

PMID- 19182528
TI  - Reversible whole-organism cell cycle arrest in a living vertebrate.
AB  - In vivo cell cycle analysis in higher eukaryotes has been limited by the
      challenge of preserving the integrity of the living organism while visualizing
      dividing cells. Here, we propose a new model, which uses the unique combination
      of features of the Japanese medaka in order to visualize and manipulate the cell
      cycle progression in a live vertebrate. Our stable transgenic histone H2B-GFP
      medaka line allows fluorescence-based monitoring of the chromosomes. The system
      has a high specificity, with a strong GFP signal labeling the chromatin
      architecture. The subcellular resolution ensures detection of both normal and
      abnormal divisions in live recordings. This translates into the possibility to
      quantify temporal and spatial aspects of the cell cycle, such as length or
      nuclear size, as well as to expose drug toxicity at the earliest stage. We also
      show that acclimation to cold, a prominent feature of the eurytherm medaka, is a
      valuable natural way of inducing a reversible cell cycle arrest in the entire
      living organism. Our results suggest that this manipulation can be performed from
      the early stages of development, has no toxicity and does not alter the cell
      cycle profile of the embryo.

PMID- 19182529
TI  - Methodological considerations for assessing autophagy modulators: a study with
      calcium phosphate precipitates.
AB  - Autophagy has been implicated in various physiological and disease conditions in
      recent years. A number of small molecule modulators have been identified, both as
      tools and as potential therapeutics. Despite extensive characterization of
      autophagy in yeast, mammalian autophagy pathways are not fully understood.
      Recently, calcium phosphate precipitates (CPP), which are used to transfect DNA
      into cells, were reported to induce autophagy, when assayed up to 6 h after
      treatment. Because of the widespread use of this reagent, we attempted to confirm
      these findings. Consistent with the previous study, we showed that CPP induces
      autophagosome synthesis at early time points, such as 4 h and 6 h. However, at 24
      h after treatment, we were surprised to see that autophagy flux was reduced, due
      to impaired autophagosome-lysosome fusion. At this time point, there was an
      accumulation of autophagy substrates and the formation of abnormally large
      autophagosomes. Thus, one may need to consider assaying autophagy modulators at
      different time points with a range of assays in order to understand their
      effects. Finally, the complex consequences of CPP on autophagy suggest that it is
      best avoided as a transfection reagent in studies aiming to analyze autophagy
      itself, or processes that are modulated by autophagy, like apoptosis.

PMID- 19182530
TI  - TAp73alpha binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy.
AB  - Aneuploidy is a characteristic of most solid tumors, often associated with
      negative prognosis. It can arise from two principal mechanisms: from a tetraploid
      intermediate state, or directly from errors at cell division. The control of cell
      division, crucial to maintain genomic stability, is still poorly understood in
      its relationship to aneuploidy. Here we show that the TAp73alpha isoform induces
      polyploidy when overexpressed. This is possibly due to the interaction of
      TAp73alpha with kinetochore-related proteins leading to the alteration of mitotic
      checkpoint abilities. TAp73alpha but not p53 or any of the other p73 isoforms
      binds Bub1 and Bub3. Since TAp73alpha is frequently overexpressed in cancer, this
      interaction may contribute to the aneuploidy observed in cancer progression. Our
      results suggest a novel molecular mechanism leading to aneuploidy involving
      interference of TAp73alpha with Bub1 and Bub3 resulting in an altered mitotic
      checkpoint.

PMID- 19182531
TI  - Pyk2 and Cyr61 at the cross-road of cAMP-dependent signalling in invasiveness and
      neuroendocrine differentiation of prostate cancer.

PMID- 19182533
TI  - Perplexing bodies: The putative roles of P-bodies in neurons.
AB  - Processing bodies (P-bodies) have recently come to the fore as important cellular
      sites of mRNA degradation and translational silencing. Despite these central
      functions in the control of gene expression, the roles of P-bodies have only been
      characterized in a limited number of cell types and physiological contexts.
      Neurons are highly plastic cells that undergo dynamic changes as new connections
      are made or existing ones modified. This neuronal plasticity relies, in part, on
      the local synthesis of proteins from localized mRNAs. A strict control of the
      translation and turnover of these localized mRNAs, both in terms of which
      proteins are synthesized and when and where they are produced, is a key
      prerequisite for this process to be synapse-specific. Despite recent advances,
      the molecular mechanisms mediating this control remain largely elusive. The
      discovery of P-bodies in neuronal dendrites near synapses and their response to
      stimuli involved in neuronal plasticity raises the interesting hypothesis that P
      bodies might be a component of the cellular machinery that controls neuronal
      plasticity and thereby processes such as learning and memory.

PMID- 19182532
TI  - Multiple roles for Puralpha in cellular and viral regulation.
AB  - Pur-alpha is a ubiquitous multifunctional protein that is strongly conserved
      throughout evolution, binds to both DNA and RNA and functions in the initiation
      of DNA replication, control of transcription and mRNA translation. In addition,
      it binds to several cellular regulatory proteins including the retinoblastoma
      protein, E2F-1, Sp1, YB-1, cyclin T1/Cdk9 and cyclin A/Cdk2. These observations
      and functional studies provide evidence that Puralpha is a major player in the
      regulation of the cell cycle and oncogenic transformation. Puralpha also binds to
      viral proteins such as the large T-antigen of JC virus (JCV) and the Tat protein
      of human immunodeficiency virus-1 (HIV-1) and plays a role in the cross
      communication of these viruses in the opportunistic polyomavirus JC (JCV) brain
      infection, progressive multifocal leukoencephalopathy (PML). The creation of
      transgenic mice with inactivation of the PURA gene that encodes Puralpha has
      revealed that Puralpha is critical for postnatal brain development and has
      unraveled an essential role of Puralpha in the transport of specific mRNAs to the
      dendrites and the establishment of the postsynaptic compartment in the developing
      neurons. Finally, the availability of cell cultures from the PURA knockout mice
      has allowed studies that have unraveled a role for Puralpha in DNA repair.

PMID- 19182534
TI  - Gefitinib in lung cancer therapy: clinical results, predictive markers of
      response and future perspectives.
AB  - Over the past few years, epidermal growth factor receptor has emerged as one of
      the most important targets in tumorgenesis and several drugs targeting signal
      transduction pathways have been developed. The first among these agents to be
      approved for the treatment of NSCLC was gefitinib, a potent, selective and
      reversible inhibitor of HER1/EGFR tyrosine kinase activity. The review summarizes
      its clinical development and the new therapeutic options, with particular focus
      on predictive markers of susceptibility to this drug.

PMID- 19182535
TI  - Dramatic and durable efficacy of imatinib in an advanced angiosarcoma without
      detectable KIT and PDGFRA mutations.
AB  - The tyrosine kinase (TK) inhibitor, imatinib, has revolutionized therapy of
      malignancies that are addicted to one of its target kinases, c-abl, c-kit and
      PDGF-R. This addiction is generally dependent on the acquisition of an activating
      kinase mutation, e.g., the bcr-abl fusion gene in chronic myeloid leukemia, or
      point mutations of KIT or PDGFRA in gastrointestinal stroma tumors (GIST). Other
      types of sarcomas are generally considered to be insensitive to imatinib. We have
      observed a striking and durable remission of an advanced angiosarcoma to imatinib
      that can only be explained by TK addiction. Unexpectedly, GIST-type KIT and
      PDGFRA mutations were absent in this case. This case illustrates the diagnostic
      challenges in identifying individual candidate patients for TK inhibitor therapy.

PMID- 19182536
TI  - Localization, anchoring and translational control of oskar, gurken, bicoid and
      nanos mRNA during Drosophila oogenesis.
AB  - mRNA localization, and translation that is regulated spatially and temporally,
      are key mechanisms in the execution of polarized developmental programs. For over
      two decades, the Drosophila oocyte has served as a valuable model to study these
      mechanisms. Genetic and biochemical studies in flies have greatly contributed to
      the identification and understanding of factors that govern RNA localization and
      translational control. Embryonic axis formation is mediated through the
      subcellular localization and precise translational regulation of four key
      determinant mRNAs during oogenesis encoded by oskar, bicoid, gurken and nanos. In
      this review we aim to summarize recent insights into the mechanisms governing the
      asymmetric distribution and translation of these mRNAs.

PMID- 19182537
TI  - Autophagy induction by trehalose counteracts cellular prion infection.
AB  - Prion diseases are fatal neurodegenerative and infectious disorders for which no
      therapeutic or prophylactic regimens exist. In search of cellular mechanisms that
      play a role in prion diseases and have the potential to interfere with
      accumulation of intracellular pathological prion protein (PrP(Sc)), we
      investigated the autophagic pathway and one of its recently published inducers,
      trehalose. Trehalose, an alpha-linked disaccharide, has been shown to accelerate
      clearance of mutant huntingtin and alpha-synuclein by activating autophagy,
      mainly in an mTOR-independent manner. Here, we demonstrate that trehalose can
      significantly reduce PrP(Sc) in a dose- and time-dependent manner while at the
      same time it induces autophagy in persistently prion-infected neuronal cells.
      Inhibition of autophagy, either pharmacologically by known autophagy inhibitors
      like 3-methyladenine, or genetically by siRNA targeting Atg5, counteracted the
      anti-prion effect of trehalose. Hence, we provide direct experimental evidence
      that induction of autophagy mediates enhanced cellular degradation of prions.
      Similar results were obtained with rapamycin, a known inducer of autophagy, and
      imatinib, which has been shown to activate autophagosome formation. While
      induction of autophagy resulted in reduction of PrP(Sc), inhibition of autophagy
      increased the amounts of cellular PrP(Sc), suggesting that autophagy is involved
      in the physiological degradation process of cellular PrP(Sc). Preliminary in vivo
      studies with trehalose in intraperitoneally prion-infected mice did not result in
      prolongation of incubation times, but demonstrated delayed appearance of PrP(Sc)
      in the spleen. Overall, our study provides the first experimental evidence for
      the impact of autophagy in yet another type of neurodegenerative disease, namely
      prion disease.

PMID- 19182538
TI  - Defining microenvironments within mouse models that enhance tumor aggressiveness.

PMID- 19182540
TI  - Intercepting Akt with DNAzyme: A nasopharyngeal carcinoma story.

PMID- 19182541
TI  - Dissecting the genetics of longevity in Drosophila melanogaster.
AB  - Drosophila melanogaster has been an historically important system for
      investigating the genetic basis of longevity, and will continue to be valuable as
      new technologies permit genomic explorations into the biology of aging. The
      utility of D. melanogaster resides in two resources: its powerful genetic tools
      as a model system, and a natural ecology that provides substantial genetic
      variation across significant environmental heterogeneity. Here we provide a
      review of the genetics of longevity in D. melanogaster, in which we describe the
      characterization of individual aging genes, the complexity of the genetic
      architecture of this quantitative trait, and the evaluation of natural genetic
      variation in the evolution of life histories.

PMID- 19182543
TI  - Fly takes off.

PMID- 19182542
TI  - MAPK signaling in equations and embryos.
AB  - The Extracellularly Regulated Kinase/Mitogen Activated Protein Kinase (ERK/MAPK)
      signaling pathway is a critical regulator of cellular processes in adult and
      developing tissues. Depending on the cellular context, MAPK cascade can act as a
      rheostat, a switch, or an oscillator. The highly conserved structure of the
      cascade does not imply a rigid function, as was suggested by the early
      mathematical models of MAPK signaling, and can instead produce a wide range of
      input-output maps. Given a large number of pathway components and modes of
      regulation, it is essential to establish experimental systems that will allow
      both manipulating the MAPK cascade and monitoring its dynamics. The terminal
      patterning system in the Drosophila embryo appears to be ideally suited for this
      purpose. Our recent experiments characterized dynamics of the MAPK
      phosphorylation gradient in the terminal system and proposed that it is regulated
      by a cascade of diffusion-trapping modules. Here we discuss a biophysical model
      that can describe the observed dynamics and guide future experiments for
      exploring the relative importance of multiple layers of MAPK cascade regulation.

PMID- 19182539
TI  - Fruit flies and intellectual disability.
AB  - Mental retardation--known more commonly nowadays as intellectual disability--is a
      severe neurological condition affecting up to 3% of the general population. As a
      result of the analysis of familial cases and recent advances in clinical genetic
      testing, great strides have been made in our understanding of the genetic
      etiologies of mental retardation. Nonetheless, no treatment is currently
      clinically available to patients suffering from intellectual disability. Several
      animal models have been used in the study of memory and cognition. Established
      paradigms in Drosophila have recently captured cognitive defects in fly mutants
      for orthologs of genes involved in human intellectual disability. We review here
      three protocols designed to understand the molecular genetic basis of learning
      and memory in Drosophila and the genes identified so far with relation to mental
      retardation. In addition, we explore the mental retardation genes for which
      evidence of neuronal dysfunction other than memory has been established in
      Drosophila. Finally, we summarize the findings in Drosophila for mental
      retardation genes for which no neuronal information is yet available. All in all,
      this review illustrates the impressive overlap between genes identified in human
      mental retardation and genes involved in physiological learning and memory.

PMID- 19182544
TI  - Inside FlyBase: biocuration as a career.
AB  - As research in the biological sciences continues to advance at a rapid pace, it
      is increasingly important that the data be captured, standardized, organized and
      made accessible to the scientific community. This is the job of a biocurator.
      Here we describe the process of biocuration from our perspective as FlyBase
      curators.

PMID- 19182547
TI  - Advancing evidence-based practice in rural nursing.
AB  - The Iowa Model of Evidence-Based Practice is an organizational change model.
      Little research has been done using the model at rural hospitals. This pilot
      study examined evidence-based practice at a rural hospital. Data were collected
      pre and post staff development. Most nurses had limited prior understanding. At
      follow-up, they reported the need for ongoing support. The first steps of the
      Iowa Organizational Change Model, even after staff development, presented
      barriers.

PMID- 19182546
TI  - Use of a handheld computer observational tool to improve communication for care
      planning and psychosocial well-being.
AB  - Staff development nurses in long-term care are challenged to implement training
      programs that foster quality unlicensed assistive personnel (UAP) care and
      improve the transfer of their observations to licensed nursing staff for care
      planning. This study describes the outcomes of a program where UAP recorded
      behavioral problems of residents to inform care. Findings suggest that staff
      development nurses who aim to improve UAP reporting without simultaneously
      targeting licensed nursing staff behaviors may worsen nursing staff
      relationships.

PMID- 19182548
TI  - The perception of learning and satisfaction of nurses in the online environment.
AB  - Despite the education challenges faced by healthcare institutions, the use of
      online technology (eLearning) to demonstrate competency for practicing nurses in
      the acute care environment has only recently been explored. The authors discuss
      the implementation of an online-based nursing education competency. The results
      demonstrate that the use of the eLearning format provides both a satisfactory and
      effective alternative learning medium. The study provides support for the use of
      online learning in the healthcare setting.

PMID- 19182549
TI  - Celebrating our 25th year of publication.

PMID- 19182550
TI  - Preparation for a bariatric center of excellence site survey: the educator's
      perspective.
AB  - Morbid obesity continues to be a growing problem in the United States. Between
      1997 and 2003, the number of U.S. hospitals offering bariatric surgery has nearly
      tripled. Confronted with increasing demands for bariatric surgery, competency of
      nursing staff caring for the bariatric surgery patient has emerged as a key area
      of focus. This article highlights the innovative creation and implementation of a
      bariatric surgery competency program that would meet the competency standards for
      a Bariatric Surgery Center of Excellence.

PMID- 19182545
TI  - Genetic control of programmed cell death (apoptosis) in Drosophila.
AB  - Programmed cell death, or apoptosis, is a highly conserved cellular process that
      has been intensively investigated in nematodes, flies and mammals. The genetic
      conservation, the low redundancy, the feasibility for high-throughput genetic
      screens and the identification of temporally and spatially regulated apoptotic
      responses make Drosophila melanogaster a great model for the study of apoptosis.
      Here, we review the key players of the cell death pathway in Drosophila and
      discuss their roles in apoptotic and non-apoptotic processes.

PMID- 19182552
TI  - Decreasing performance and test anxiety in practicing nurses.
AB  - Many nurses are being required to pass competency and certification examinations
      to keep or advance in their positions. Unfortunately, anxiety often dampens the
      nurse's ability to demonstrate competence in a particular area of practice. The
      dimensions of test anxiety are explained, and signs and symptoms are described.
      Basic intervention strategies are included to guide educators in helping staff
      with performance and test anxiety.

PMID- 19182554
TI  - From novice to advanced beginner: the critical care internship.
AB  - Our unit is a 12-bed medical-surgical intensive care unit in a small central
      Florida community. Finding experienced critical care nurses to fill vacancies is
      very difficult. We have offered a critical care internship for the past few years
      to attempt to augment our staff. Without the resources of a unit-based educator
      or clinical nurse specialist and with a very limited budget, we are committed to
      improving our internship to provide us with safe, competent critical care nurses
      who are willing to become members of our team. A literature review was conducted,
      and recommendations were developed to improve our current internship to better
      meet the needs of the unit and the beginning critical care nurses.

PMID- 19182555
TI  - The exploration of the lived experience of the graduate nurse making the
      transition to registered nurse during the first year of practice.
AB  - The purpose of this study was to gain insight into the transition period of
      graduate nurses. A phenomenological research approach was used to explore the
      lived experiences of graduate nurses during their first year of employment.
      Content analysis resulted in five thematic areas identified as indicators of a
      positive transition experience. The findings of this study provide information
      for staff development instructors, nurse managers, and nurse administrators in
      identifying practice environment characteristics and initiatives that promote a
      positive transition period for graduate nurses and increased retention in initial
      areas of nursing practice.

PMID- 19182556
TI  - Preceptor perceptions of new graduate nurse readiness for practice.
AB  - Preparing nursing graduates for entry into practice is a priority for academic
      and healthcare institutions. To effectively prepare competent entry-level
      practitioners, it is important to understand clinical agency expectations. Most
      clinical agencies utilize some form of a precepted orientation experience for new
      graduate nurses. The purpose of this study was to examine preceptors' perceptions
      of the competence of new graduate nurses. Data analysis indicated several areas
      of weakness in new graduate nurses' clinical skills. This information can be used
      by academic nursing programs to revise clinical experiences to better prepare
      graduates for entry into practice. Findings can also be utilized to assist
      healthcare institutions with designing orientation programs for new graduate
      nurses. Suggestions are provided to help train preceptors for their important
      role. It is essential, particularly in today's complex healthcare environment,
      that strategies be explored to facilitate success of the emerging nursing
      workforce.

PMID- 19182558
TI  - Making sense of the legislative process: a report from the NNSDO legislative
      liaison.

PMID- 19182557
TI  - Staff development story: Concept mapping: a staff development strategy for
      enhancing oncology critical thinking.

PMID- 19182559
TI  - The psychotherapies.

PMID- 19182560
TI  - The Y model: an integrated, evidence-based approach to teaching psychotherapy
      competencies.
AB  - OBJECTIVE: The authors' goal was to develop an integrated model for teaching
      psychotherapy competencies across schools of therapy. METHOD: The authors
      surveyed the comparative psychotherapy process literature to identify core
      features of psychotherapy shared across schools and differentiate those features
      from the defining features of psychodynamic therapy and cognitive-behavioral
      therapy. RESULTS: The resulting Y Model for teaching psychotherapy competencies
      locates core processes of therapy that are shared across schools on the stem of
      the Y, differentiates psychodynamic therapy and cognitive-behavioral therapy on
      the branches of the Y, and locates supportive therapy largely on the stem of the
      Y. CONCLUSIONS: The Y Model offers an efficient, integrated, evidence-based
      system for teaching psychotherapy competencies across schools in a conceptually
      clear way that is free of competition and bias between schools.

PMID- 19182561
TI  - Community-based psychodynamic treatment program for severe personality disorders:
      clinical description and naturalistic evaluation.
AB  - Long-term inpatient treatment for personality disorders has become infrequent in
      the last two decades, and the gap left in service provision has been filled by
      psychodynamically and cognitively oriented partial hospitalization and
      outpatient, community-based approaches. It is still uncertain how these low-cost,
      lower-intensity models have fared relative to residential models that treat
      patients with severe personality disorders with the containment and control
      offered by the inpatient setting. In this article, we describe key features of a
      community-based psychodynamic program developed at the Cassel Hospital in the
      United Kingdom and present preliminary findings of a 2-year prospective
      naturalistic outcome study that monitored psychiatric morbidity (Brief Symptom
      Inventory General Severity Index [BSI-GSI]) and clinical outcome (self
      mutilation, suicide attempts, and hospital admissions) in 68 patients with
      personality disorders who were consecutively admitted to the program.
      Improvements shown by the community-based sample on all variables were compared
      with the results in a comparable sample of inpatients treated in a long-term
      psychosocial treatment program in the same institution. The naturalistic
      comparison of the two non-randomized treatment models revealed that the community
      based sample improved to a significantly greater degree on all three clinical
      outcome dimensions and had significantly lower early dropout rates than those who
      received the long-term residential treatment. The findings indicate that, at
      least in terms of impulsive behavior and treatment adherence, the community-based
      program appears to offer a viable adequate alternative to long-term inpatient
      admission.

PMID- 19182562
TI  - Formulating transference in cognitive and dynamic psychotherapies using role
      relationship models.
AB  - Configurational analysis, a system that can be used to organize formulations of
      transference phenomena, may be helpful to cognitive behavioral as well as
      psychodynamic therapists. We interviewed 41 experienced psychotherapists, 24 of
      whom were psychodynamic therapists and 17 of whom were cognitive-behavioral
      therapists. The therapists first each rated one of their well-known patients on a
      list of 12 simple positive and negative transferences. Next, they described the
      patient's transference in their own words. After that, each therapist formulated
      the same patient's transference contents according to a more complex format, the
      Role Relationships Model Configuration (RRMC). Both groups reported relatively
      similar levels of both positive and negative transference reactions. Both groups
      found the RRMC format useful, with 38 (92.7%) of the 41 therapists indicating
      that they found the RRMC method "moderately" to "very" useful. Using the RRMC as
      a structured approach to identify and describe transference and relationship
      patterns appears to be helpful to psychotherapists with different theoretical
      orientations.

PMID- 19182563
TI  - Medication adherence: a review of the literature and implications for clinical
      practice.
AB  - Adherence is defined as the extent to which a patient's behavior coincides with
      medical or prescribed health advice. Adherence is considered non-judgmental and
      is preferred over the term "compliance," which carries negative connotations and
      suggests blame for the patient. A major challenge in the field of psychiatry has
      been to understand why patients may or may not adhere to medication and other
      treatment recommendations. A comprehensive review of the literature on medication
      adherence among patients with psychiatric illnesses was conducted with the
      following objectives: (1) to better understand the impact of medication
      nonadherence, (2) to identify risk factors for medication nonadherence, and (3)
      to study interventions designed to improve patient adherence. The authors
      initially searched the Ovid Medline electronic database using the key words
      "medication adherence" and "compliance" to identify all articles written in the
      English language published through early 2008. This produced over 2000
      references. The search was then narrowed to publications specific to psychotropic
      medication. The ultimate goal of the review was to increase awareness of this
      critical issue and to discuss strategies that the psychiatric clinician can
      implement to address patient adherence to prescribed medications. The authors
      chose to include articles that were deemed to be clinically useful to the
      practicing clinician.Studies that have specifically investigated adherence to
      psychiatric medications vary in the definitions of adherence and methodology that
      were used, making interpretation of results across studies difficult.
      Psychoeducational interventions have long been the mainstay of treatment for
      adherence problems. However, there is growing evidence that other approaches such
      as cognitive-behavioral strategies and motivational interviewing may be
      effective. Based on a comprehensive literature review, the authors recommend the
      following strategies for addressing adherence problems: focus on strengthening
      the therapeutic alliance; devote time in treatment specifically to address
      medication adherence; assess patients' motivation to take prescribed medications;
      and identify and address potential barriers to treatment adherence.

PMID- 19182564
TI  - Results of the STAR*D study: implications for clinicians and drug developers.

PMID- 19182565
TI  - The compleat psychiatrist.

PMID- 19182566
TI  - The psychological autopsy, part II: toward a standardized protocol.

PMID- 19182567
TI  - Neurotoxicity with therapeutic lithium levels: a case report.
AB  - This case report describes the history and hospital course of an otherwise
      healthy 20-year-old male with bipolar I disorder who developed symptoms of severe
      lithium toxicity, culminating in a seizure, despite a level of lithium of only
      0.8 mEq/L, within the usual therapeutic range. The discussion emphasizes that
      lithium toxicity is diagnosed by clinical symptoms and can occur even at usual
      therapeutic blood levels.

PMID- 19182568
TI  - Safe return to homeland of an illegal immigrant with psychosis.
AB  - The disposition of illegal immigrants who lack social support and wish to return
      to their homeland is a frequent and difficult challenge for many mental health
      facilities in the United States. This case involved an undocumented Mexican
      patient with severe psychosis who was safely transferred to his hometown
      according to his and his family's wishes through the use of specific services
      provided by the Mexican Consulate. We hope that publication of this case will
      make the medical community more aware of the availability of these underused
      services, which can make a major difference in the prognosis of some undocumented
      patients who would otherwise be left without resources or appropriate care.

PMID- 19182569
TI  - Does exercise impact mood? Exercise patterns of patients in a psychiatric partial
      hospital program.
AB  - OBJECTIVE: To examine the exercise patterns of patients in a partial hospital
      (PH) program and to determine whether these patterns are associated with mood
      symptoms and body mass index (BMI). Methods. Eighty-six participants completed
      self-report questionnaires upon entry to the PH program. We conducted regression
      analyses to determine the association of exercise, mood, and BMI. Results. We
      found that the participants' exercise history did not predict automatic thoughts
      or depressive symptoms. Current exercise did predict fewer depressive symptoms
      and lower BMI, but not automatic thoughts. A majority of participants were
      overweight and reported not exercising, despite acknowledging that they were not
      physically fit and that exercise is beneficial. Conclusion. We recommend that
      exercise programs be piloted in PH settings to improve patients' mental as well
      as physical health. Future research should further examine obstacles to
      exercising in clinical populations.

PMID- 19182570
TI  - Advances in extensor tendon diagnosis and therapy.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Identify clinical situations in which hand sonography can result in the
      detection of partial extensor tendon tears. 2. Identify the limitations of
      magnetic resonance imaging in diagnosing extensor tendon tears. 3. Understand the
      various postoperative therapeutic protocols for extensor tendon repair. 4. Choose
      the appropriate surgical repair and postoperative therapeutic protocol for a
      specific extensor tendon injury. 5. Identify the social and economic variables
      that may influence the availability and efficacy of the various postoperative
      therapeutic protocols. BACKGROUND: This article describes how the application of
      radiographic imaging facilitates the earlier detection and differentiation of
      extensor tendon injuries. Furthermore, it defines the best surgical procedure and
      postoperative therapy for a specific injury. METHODS: A literature review was
      performed of extensor tendon injury articles published since 1989. RESULTS: High
      resolution sonography was more accurate than physical examination and magnetic
      resonance imaging in detecting extensor tendon injuries. Traditional
      postoperative static splinting was equivalent to early motion protocols for all
      uncomplicated thumb injuries and zone 1 to 3 injuries of the second through fifth
      digits. The only definable benefit of early motion therapy compared with static
      splinting was a quicker return to final function for proximal zones of injury in
      the second through fifth digits. The results of early active and passive motion,
      measured at 6 months, were comparable to those from static splinting. A higher
      rupture rate for early active motion and greater cost for early active and
      passive motion were noted compared with static splinting. CONCLUSIONS: High
      resolution sonography allows identification of difficult to diagnose partial and
      complete extensor tendon injuries. Static splinting should remain the
      postoperative standard of care for extensor tendon injuries to the thumb and
      distal zones of injury for digits 2 through 5. The best therapy protocol for
      proximal zones of injury should be individualized based on social and economic
      variables.

PMID- 19182571
TI  - Collection of bone dust: a new technique.

PMID- 19182572
TI  - Delineating curettage as an adjunct to excision of Basal cell carcinoma: results
      in 334 cases.

PMID- 19182573
TI  - Intralesional hemorrhage in venous malformations.

PMID- 19182574
TI  - Surgical adhesive tape for facial rejuvenation.

PMID- 19182575
TI  - Reorienting the vector in facial reanimation using an estlander flap.

PMID- 19182576
TI  - The future of rhinoplasty and the Dallas rhinoplasty symposium.

PMID- 19182577
TI  - One-stage reconstruction of the nasal ala: the free-style nasolabial perforator
      flap.

PMID- 19182578
TI  - The lip-to-tip flap: a method of reconstructing nasal tip defects.

PMID- 19182579
TI  - A congenital cleft of the alar rim.

PMID- 19182580
TI  - Postmaxillectomy prognathism.

PMID- 19182581
TI  - A late complication of fat autografting in breast augmentation.

PMID- 19182582
TI  - Temporary remission of a multirecurrent cystosarcoma phyllodes of the breast by
      using continuous chemotherapy.

PMID- 19182583
TI  - Axillary ectopic breast tissue during pregnancy following augmentation
      mammaplasty.

PMID- 19182584
TI  - The use of porcine acellular dermal material for TRAM flap donor-site closure.

PMID- 19182585
TI  - Additional uses for a barrier drape in breast implant surgery.

PMID- 19182586
TI  - Treatment of life-threatening surgical emphysema with liposuction.

PMID- 19182587
TI  - Accidental pull-out of drains after abdominoplasty: outpatient endoscopic control
      of an expanding hematoma and reinstallation of drains under direct vision without
      opening the wound.

PMID- 19182588
TI  - Prone positioning in large-volume liposuction.

PMID- 19182589
TI  - Cause of axillary bromidrosis.

PMID- 19182590
TI  - Alternative aesthetic incisions for fixation of hand fractures.

PMID- 19182591
TI  - Malignant peripheral nerve sheath tumor of the hand.

PMID- 19182592
TI  - Covering the popliteal fossa defect with the fasciocutaneous cone flap.

PMID- 19182593
TI  - Long-term follow-up of the treatment of lower limb lymphedema with liposuction.

PMID- 19182594
TI  - Diffuse squamous cell carcinoma in porokeratotic eccrine ostial and dermal duct
      nevus.

PMID- 19182595
TI  - Revisiting fresh fibroblast allograft as a treatment for diabetic foot ulcers.

PMID- 19182596
TI  - Evidence-based plastic surgery.

PMID- 19182597
TI  - Basic plastic surgery training using human skin.

PMID- 19182598
TI  - More of a good thing: time for more time outs.

PMID- 19182599
TI  - Selective breast reduction: a personal approach with a central-superior pedicle.
AB  - BACKGROUND: Breast reduction shows a greater risk of complications in peculiar
      cases such as those with gigantomastia, a high degree of ptosis, obesity,
      smoking, cardiovascular diseases, or metabolic disorders. The authors feel that a
      reduction in the complication rate can be achieved by safeguarding the vascular
      and nervous structures of the breast as much as possible. METHODS: The authors
      propose a breast reduction method based on a double central-superior pedicle that
      was used in 91 patients with a more or less elevated degree of obesity. This
      technique aims to remove excess tissue, preserving the noble structures of the
      breast. Beginning from preoperative drawings similar to the ones of Lejour,
      deepithelialization and wide medial and lateral skin undermining are performed.
      Next, the excess tissue is removed from the caudal, medial, and lateral portions
      of the breast and from the deep cranial portion, sparing the horizontal septum
      that supplies vessels and nerves to the nipple. A "handle" composed of the
      superior and central pedicles is obtained. After fixing the central pedicle to
      the thoracic wall, redundant skin is removed, and a vertical or J-shaped suture
      is made. RESULTS: The authors obtained good breast shape, short scars, and
      optimal viability of the nipple-areola complex. The results are stable and
      durable, and the complication rate seems to be very low. CONCLUSIONS: The authors
      believe that this technique may be a valid alternative to traditional methods,
      especially in vast tissue resections and in cases of considerable nipple-areola
      complex lift. It is mainly indicated in obese and partial weight loss patients.

PMID- 19182600
TI  - Septum-based mammaplasty: a surgical technique based on Wuringer's septum for
      breast reduction.
AB  - BACKGROUND: During the past 7 years, the senior author (M.H.) has been performing
      septum-based mammaplasty. The aim of this article is to report the safety and
      ease of breast shaping by using this technique. METHODS: A series of 110
      consecutive patients underwent septum-based breast reduction performed by a
      single surgeon. This technique uses a lateral or medial pedicle based on
      Wuringer's horizontal septum, which carries the main nerve supply to the nipple
      in addition to intercostal perforators. RESULTS: Mean nipple-to-sternal notch
      distance was 33 cm (range, 22 to 45 cm). Mean resection was 658 g (range, 160 to
      1980 g). Nipple elevation was 9 cm on average (range, 3 to 17 cm). A retroareolar
      hematoma occurred in three breasts. Total areola necrosis occurred in one breast
      (0.5 percent) as a result of an infection in a diabetic patient. Limited wound
      dehiscence occurred in 15 breasts (7.7 percent). A secondary scar revision was
      needed in 10 patients (9 percent). One patient required a revision. CONCLUSIONS:
      Based on a well-vascularized and constant anatomical septum, a septum-based
      pedicle is safe, even in large breasts. This technique is safe and demonstrates
      ease of pedicle shaping and breast remodeling in patients undergoing reduction
      mammaplasty.

PMID- 19182601
TI  - Shaping the breast in aesthetic and reconstructive breast surgery: an easy three
      step principle.
AB  - Creating or recreating an aesthetically pleasing breast shape in reconstructive
      and aesthetic breast surgery is an act that most experienced "breast" surgeons
      will find self-evident. We propose a simple three-step philosophical and hands-on
      approach that will make it easier for young and unexperienced plastic surgeons to
      not only analyze the problematic breast but also come up with an easy surgical
      strategy to create reproducible results.This is Part I of four parts describing
      the three-step principle being applied in reconstructive and aesthetic breast
      surgery. Part I explains how to analyze a problematic breast by understanding the
      three main anatomical features of a breast and how they interact: the footprint,
      the conus of the breast, and the skin envelope. Part II deals with
      reconstructions after complete mastectomy and Part III covers reconstruction
      after breast conservation surgery. Finally, Part IV applies the same principles
      in the field of aesthetic breast surgery. Throughout these four parts, the three
      step principle will be the red line to fall back on to define the problem and to
      propose a solution.

PMID- 19182602
TI  - The role of regional posterior frontal dura mater in the overlying suture
      morphology.
AB  - BACKGROUND: Craniosynostosis, the premature fusion of one or more cranial
      sutures, is a common developmental disorder resulting in morphologic and
      functional consequences. The rat model is useful for studying pathologic and
      normal suture fusion because the posterior frontal suture undergoes fusion but
      the remaining sutures remain patent. The authors investigated the influence of
      regional posterior frontal dura mater on the overlying suture morphology and
      fate. METHODS: In 8-day-old Sprague-Dawley rats, an 8-mm calvarial disk was
      excised without disrupting the underlying dura mater (n = 22) and flipped so that
      the previously ectocranial aspect was adjacent to the dura mater. The animals
      were humanely killed after 5, 7, 9, 11, and 28 days, and the posterior frontal
      sutures were analyzed histologically. A comparison was made to control animals in
      which the disk was excised and then placed back into its anatomical position (n =
      5). Immunohistochemistry of the transforming growth factor (TGF)-beta isoforms
      was performed to investigate their differential, temporal, and spatial
      expression. RESULTS: Posterior frontal suture fusion occurred on the side
      adjacent to the dura mater (previously patent ectocranial aspect) in an anterior
      to-posterior direction, similar to that in the control group. There was specific
      expression of the TGF-beta isoforms in the dura mater and suture mesenchyme
      adjacent to the dura mater. CONCLUSIONS: Regional dura mater plays an important
      role in suture morphology, and the posterior frontal-associated dura mater
      possesses potent, pro-osteogenic signals that influence the overlying suture
      fate. The differential expression pattern of TGF-beta signaling from the dura
      mater further supports the regional paracrine effect of the dura mater.

PMID- 19182603
TI  - Spring-assisted cranioplasty alters the growth vectors of adjacent cranial
      sutures.
AB  - BACKGROUND: Expansile cranial springs are used to treat selected cases of
      sagittal synostosis. After sagittal suturectomy, springs are placed perpendicular
      to the line of the synostosis. Normal growth across the coronal suture is
      approximately perpendicular to the suture line. To allow cranial expansion in the
      parietal direction, it is hypothesized that the normal growth vectors across the
      coronal sutures are altered. METHODS: Ten New Zealand White rabbits underwent
      suturectomy of the midline posterior frontal suture followed by insertion of an
      expansile spring. Radiologic markers were placed on either side of the normal
      coronal sutures (n = 20) perpendicular to the released suture. Serial radiology
      was performed up to 7 weeks. Growth vectors across the coronal suture were
      compared with those of 10 control rabbits. RESULTS: Dorsal cranial expansion was
      predominantly in an anterolateral direction in controls. The normal growth vector
      across the coronal suture occurred at an angle of -1 degree to the midline. A
      spring altered this growth vector to 63 degrees. Over 7 weeks, the cranial width
      increased 5.1 mm in rabbits with springs compared with 0.2 mm in the control
      group (p < 0.01). The increase in cranial length across the coronal suture was
      1.82 mm in controls and 0.93 mm in rabbits with springs (p = 0.019). CONCLUSIONS:
      Application of a spring across a midline cranial suture alters the growth vector
      of the normal adjacent sutures. The spring greatly increases cranial width at the
      expense of some of the normal increase in cranial length over this period. This
      would be beneficial in correcting the cranial index in sagittal synostosis.

PMID- 19182605
TI  - The role of the neuropeptide Y2 receptor in liporemodeling: neuropeptide Y
      mediated adipogenesis and adipose graft maintenance.
AB  - BACKGROUND: Neuropeptide Y is a signaling molecule that was recently found to
      stimulate adipose tissue growth in vitro by means of a peripherally acting
      mechanism involving the neuropeptide Y2 receptor found on adipocytes and
      endothelial cells. This study aims to evaluate the translational applications of
      a neuropeptide Y2 receptor agonist for autologous fat grafting in plastic
      surgery. METHODS: Murine and primate animal models were used to investigate the
      proliferative effects of neuropeptide Y on adipose tissue. The effect of applying
      neuropeptide Y to subcutaneous tissues in mice and monkeys was assessed by
      magnetic resonance imaging, histology, and immunohistochemistry. The effect of
      neuropeptide Y on human fat xenograft survival and vascularity in athymic mice
      was measured by ultrasonography and immunohistochemistry. Six animals per group
      were used in murine experiments, and two animals were used in the pilot primate
      study. RESULTS: Neuropeptide Y stimulated growth of adipose tissues when applied
      subcutaneously in mice and monkeys, and increased human fat xenograft survival
      and vascularity in athymic mice at 3 months. CONCLUSIONS: These data provide in
      vivo evidence for a critical role for neuropeptide Y/neuropeptide Y2 receptor
      interactions in adipogenesis, and suggest neuropeptide Y2 receptor as a potential
      target for agonist compounds that can be used to enhance fat graft survival or
      stimulate de novo adipogenesis.

PMID- 19182606
TI  - Facial subunit composite tissue allografts in nonhuman primates: I. Technical and
      immunosuppressive requirements for prolonged graft survival.
AB  - BACKGROUND: Widespread application of composite tissue allotransplantation has
      been impeded by risks of rejection and conventional immunosuppression. The
      authors have developed a nonhuman primate composite tissue allotransplantation
      model that demonstrated reliable and long-term success necessary to progress to
      preclinical studies. METHODS: Composite facial subunits (e.g., skin, muscle, and
      bone) were transplanted between mismatched cynomolgus monkeys. Vascular supply
      was based on the common carotid artery and external and internal jugular veins.
      Facial allografts were heterotopically transplanted to the recipient's lower
      abdomen with end-to-side anastomoses of the common carotid artery to the common
      femoral artery and of both the internal and external jugular veins to the common
      femoral vein. Animals received tacrolimus monotherapy. Grafts were inspected
      daily, submitted to biopsy regularly, and studied with magnetic resonance
      imaging. RESULTS: Thirteen transplants were performed. Two grafts based on the
      common carotid artery and only the internal jugular vein failed within 3 to 5
      days because of venous thrombosis not related to rejection. Subsequent
      transplants included anastomoses of both the internal and external jugular veins
      to the common femoral vein without thromboses. Immunosuppression consisted of
      tacrolimus monotherapy and was tolerated without complications. Long-term success
      was achieved with rejection-free graft survival (60 to 177 days). CONCLUSIONS:
      The authors have developed the first successful model of facial composite tissue
      allotransplantation in a nonhuman primate. Technical requirements include
      preservation of both internal and external jugular venous outflow. Tacrolimus
      monotherapy permitted prolonged rejection-free graft survival without early
      complications. This model provides a platform for further investigation of
      composite tissue allotransplantation tolerance and requirements for indefinite
      survival.

PMID- 19182604
TI  - Aging and diabetes impair the neovascular potential of adipose-derived stromal
      cells.
AB  - BACKGROUND: Aging and diabetes are major risk factors for poor wound healing and
      tissue regeneration that reflect an impaired ability to respond to ischemic
      insults. The authors explored the intrinsic neovascular potential of adipose
      derived stromal cells in the setting of advanced age and in type 1 and type 2
      diabetes. METHODS: Adipose-derived stromal cells isolated from young, aged,
      streptozotocin-induced, and db/db diabetic mice were exposed to normoxia and
      hypoxia in vitro. Vascular endothelial growth factor (VEGF) expression,
      proliferation, and tubulization were measured. Conditioned media harvested from
      adipose-derived stromal cell cultures were assessed for their ability to
      stimulate human umbilical vein endothelial cell proliferation (n = 3 and n = 3).
      RESULTS: Young adipose-derived stromal cells demonstrated significantly higher
      levels of VEGF production, proliferation, and tubulogenesis than those derived
      from aged, streptozotocin-induced, and db/db mice in both normoxia and hypoxia.
      Although aged and diabetic adipose-derived stromal cells retained the ability to
      up-regulate VEGF secretion, proliferation, and tubulogenesis in response to
      hypoxia, the response was blunted compared with young controls. Conditioned media
      derived from these cells cultured in normoxia in vitro also had a significantly
      greater ability to increase human umbilical vein endothelial cell proliferation
      compared with media harvested from aged, streptozotocin-induced, and db/db
      adipose-derived stromal cells. This effect was magnified in conditioned media
      harvested from hypoxic adipose-derived stromal cell cultures. CONCLUSIONS: This
      study demonstrates that aging and type 1 and type 2 diabetes impair intrinsic
      adipose-derived stromal cell function; however, these cells may still be a
      suitable source of angiogenic cells that can potentially improve
      neovascularization of ischemic tissues.

PMID- 19182607
TI  - Activated protein C improves ischemic flap survival and modulates proangiogenic
      and antiinflammatory gene expression.
AB  - BACKGROUND: Flap necrosis remains a major complication in reconstructive surgery.
      The authors evaluated whether systemic activated protein C, a natural serum
      anticoagulant with anti-inflammatory, proangiogenic, and cytoprotective
      properties, can improve ischemic skin flap survival. METHODS: Cranially based
      dorsal cutaneous flaps were elevated on 44 rats. Animals received intravenous
      injections of activated protein C (25 microg/kg) or saline. Rats were divided
      into three groups depending on the timing of the first injection: postoperative
      (45 minutes postoperatively, n = 12), late preoperative (45 minutes
      preoperatively, n = 5), and early preoperative (3 hours preoperatively, n = 5).
      In all groups, second and third injections were performed at 3 and 24 hours
      postoperatively. Flap survival was measured on day 7. Histological and real-time
      polymerase chain reaction specimens were collected on days 2 and 7 and at 3 and
      24 hours, respectively. RESULTS: Postoperative activated protein C improved flap
      survival (68.9 +/- 4.3 percent) compared with control treatment (39.3 +/- 1.5
      percent; p < 0.001). Late preoperative treatment produced diffuse flap
      hemorrhage. Early preoperative activated protein C injection produced near
      complete flap survival (96.1 +/- 1.1 percent for activated protein C versus 50.1
      +/- 3.3 percent for control; p < 0.001). Significantly fewer inflammatory cells,
      improved muscle viability, and increased blood vessel density were observed in
      activated protein C-treated versus control rats. Activated protein C treatment
      significantly reduced mRNA levels of intercellular adhesion molecule-1 and tumor
      necrosis factor-alpha, while increasing levels of Egr-1, vascular endothelial
      growth factor receptor 2, and Bcl-2. CONCLUSIONS: Systemic activated protein C
      modulates genes involved in angiogenesis, inflammation and apoptosis and improves
      ischemic flap survival.

PMID- 19182608
TI  - The plastic surgeon's role in extracranial-to-intracranial bypass using a reverse
      great saphenous vein graft.
AB  - BACKGROUND: Extracranial-to-intracranial bypass is used for flow replacement and
      diversion that prevent the serious complications associated with sudden ligation
      of the middle cerebral artery for treatment of complex tumors or aneurysms.
      Extracranial-to-intracranial bypass is a demanding procedure that requires
      experience in advanced microsurgical techniques. In this article, the authors
      review the first report of an extracranial-to-intracranial bypass performed by a
      plastic surgeon with emphasis on indications for microsurgical involvement in
      neurosurgical practice and on description of the surgical technique. METHODS:
      Between April of 2004 and October of 2006, three extracranial-to-intracranial
      bypass cases were performed including one for a complex aneurysm rupture and two
      for resections of cranial base tumors. In every case, the intracranial approach
      was used by the neurosurgeon. The bypass was performed by interposing a reverse
      great saphenous vein graft between the superficial temporal artery, in end-to-end
      anastomosis, and the second segment of the middle cerebral artery, in end-to-side
      anastomosis. RESULTS: In each case, postoperative cerebral angiography
      demonstrated complete patency of the extracranial-to-intracranial bypass. Neither
      of the two surviving patients at a mean follow-up of 13 months had deterioration
      of neurologic function, postoperative stroke, or surgery-related death. One of
      the patients was dead before the 6-month follow-up. CONCLUSIONS: The reverse
      great saphenous vein graft is a good option for extracranial-to-intracranial
      bypass, with the advantages of high-flow graft, wide lumen, adequate length, easy
      harvest, and minimal donor-site morbidity. The plastic surgery/neurosurgery
      alliance allows scope for improved outcomes in complex neurosurgical cases and
      continues to push the frontiers of reconstructive microsurgery.

PMID- 19182610
TI  - Techniques of monitoring buried fasciocutaneous free flaps.
AB  - BACKGROUND: Although postoperative monitoring of microsurgical reconstruction is
      key to discovering early vascular compromise, monitoring a buried flap can be
      problematic. METHODS: A single surgeon's tracheal and pharyngoesophageal
      reconstructions with fasciocutaneous free flaps performed between 2002 and 2007
      are reviewed, and different monitoring techniques are described. RESULTS: Eighty
      six cases of pharyngoesophageal and eight tracheal reconstructions were
      identified. The anterolateral thigh flap was used in 78 patients and the radial
      forearm flap was used in 16 patients. Three different monitoring techniques were
      used. In group I, a component of the flap used for neck resurfacing
      simultaneously served as a monitoring segment in 59 patients. No flap compromise
      or failure occurred. In group II, either an implantable or handheld Doppler
      device was used to monitor a completely buried flap in 29 patients. The
      implantable Doppler had a false-positive rate of 31 percent, leading to
      unnecessary surgical exploration. One case each of unrecognized flap loss
      occurred with the implantable and handheld Doppler methods. In group III, a
      segment of tissue separate from the main flap but sharing the same source vessels
      was temporarily externalized for monitoring and removed before patient discharge
      in six patients. This technique was also used in a patient with an anterolateral
      thigh flap for temporal reconstruction. There was no thrombosis or flap loss in
      these patients. CONCLUSIONS: Temporarily externalizing a segment of tissue is an
      easy and reliable method for monitoring a buried fasciocutaneous free flap. It is
      important, however, to avoid obstruction at the perforator level beyond the
      common source vessels.

PMID- 19182611
TI  - Mini-temporalis transfer as an adjunct procedure for smile restoration.
AB  - BACKGROUND: The versatility of the temporalis muscle justifies its wide
      popularity in reconstructive craniomaxillofacial surgery. In late facial
      paralysis, results of neural reconstructive techniques such as cross-facial
      grafting or mini-hypoglossal-to-facial nerve transfer are partial at best. In
      this series, the authors have used a segmental temporalis transfer, the "mini
      temporalis," to augment the function attained with neural microsurgery. The aim
      of this present study was to present the experience of the authors' center with
      the use of the mini-temporalis as an adjuvant to facial nerve microsurgery for
      smile restoration. METHODS: Data were collected from 31 patients who underwent
      mini-temporalis transfer for smile restoration. In all patients, the mini
      temporalis was used to augment the results of neural reconstructive techniques.
      Opting for the mini-temporalis related to a variety of reasons, after
      preoperative evaluation was weighed against the advantages and disadvantages of
      different reconstructive strategies on individual bases. Aesthetic and functional
      outcomes were evaluated by a panel of five independent observers using a five
      category scale ranging from poor to excellent. RESULTS: All patients observed a
      follow-up longer than 3 months. Of 31 patients, 61.3 percent achieved excellent
      or good results and 29 percent achieved moderate results. All patients
      demonstrated an increase in the observers' scores after mini-temporalis transfer
      in comparison with the scores granted preoperatively or after neural
      microsurgery. Highly motivated patients committed to postoperative motor
      reeducation exhibited the best results. CONCLUSION: The clinical data presented
      support the use of mini-temporalis transposition in association with facial nerve
      microsurgery as a valuable alternative to free muscle transfer in selected cases.

PMID- 19182612
TI  - Long-term outcomes of free muscle transfer for smile restoration in children.
AB  - BACKGROUND: Evaluation of long-term outcomes of free-muscle transfer for smile
      restoration is overdue. Arguments for and against free-muscle transplantation in
      children are considered, and the debate on the influence of the growing skeleton
      on muscle function is revisited. This study evaluated the fate of free-muscle
      transfer over long follow-up periods in pediatric patients. METHODS: Thirty-two
      children with follow-up of 5 years or longer who received a free-muscle transfer
      for smile restoration were reviewed. To better analyze the effect of time,
      patients were classified into groups based on the length of follow-up: group A, 5
      to 6 years; group B, 7 to 10 years; group C, 11 to 15 years; and group D, more
      than 15 years. Patients were videotaped at three stages: preoperatively, 2 years
      after free-muscle transfer, and at the last follow-up visit. Four independent
      observers graded patients' videotapes using a five-category scale ranging from
      poor to excellent. Panelists were asked to comment on any noticeable craniofacial
      disharmony with growth. RESULTS: All patients exhibited improved function and
      symmetry at 2 years after free-muscle transfer (averaged scores, p < 0.0001). A
      positive effect of time was seen in the long-term evaluation; observers' scores
      (p < 0.0001) and motor units on electromyography (p = 0.001) showed further
      improvement. No significance was found when comparing measured outcomes among the
      four follow-up groups, indicating that despite the growing skeleton, muscle
      function was maintained over time. CONCLUSIONS: These clinical data support the
      use of free-muscle transfer for smile restoration in children. The transplanted
      muscle appears to grow harmoniously with the craniofacial skeleton, and muscle
      function and aesthetic outcomes improved over time.

PMID- 19182613
TI  - Reconstruction of facial defects using prefabricated expanded flaps carried by
      temporoparietal fascia flaps.

PMID- 19182614
TI  - Reconstruction of the upper aerodigestive tract with the submental artery flap.
AB  - BACKGROUND: : The submental artery flap has rekindled interest in using cervical
      flaps for reconstruction of head and neck defects. In this article, the authors
      present their experience with this flap for defects of the upper aerodigestive
      tract. METHODS: : This is a retrospective study of 21 patients who underwent
      upper aerodigestive tract reconstruction with submental artery flaps from 1997 to
      2005. The flap was used primarily to reconstruct defects after tumor extirpation,
      severe infections, and burns. In one case, the flap was used to close an
      esophagocutaneous fistula. Nine patients had irradiation. Three patients had flap
      prelamination before transfer. RESULTS: : The flaps in all 12 patients who had
      not undergone irradiation survived. With the exception of a small fistula in one
      patient and transient marginal mandibular nerve palsy in another, none of these
      patients experienced any major complications. In contrast, six of the nine
      patients who had been irradiated experienced major complications. These included
      total flap loss in one, partial flap losses in two, and scar contractures in
      another three. The difference in major complication rates between these two
      groups was statistically significant (0 percent versus 67 percent, p < 0.01).
      CONCLUSIONS: : In nonirradiated tissues, the submental artery flap is an
      excellent choice for reconstruction of moderate-sized defects of the upper
      aerodigestive tract because of its reliability and versatility and the ease with
      which it can be applied.

PMID- 19182615
TI  - Alternative vascular pedicle of the anterolateral thigh flap: the oblique branch
      of the lateral circumflex femoral artery.
AB  - BACKGROUND: The anterolateral thigh flap is known for variations of its vascular
      pedicle. This is a prospective intraoperative analysis of the vascular anatomy of
      the lateral thigh that focuses on clinically important variations that impact
      flap harvest. METHODS: Eighty-nine consecutive anterolateral thigh flaps were
      harvested. A detailed intraoperative analysis was performed of the vasculature
      anatomy and variations of the pedicle encountered during dissection. RESULTS:
      Fasciocutaneous flaps were harvested in 82 percent (73 of 89) and myocutaneous
      flaps were harvested in 17 percent of cases (15 of 89). Sizable perforators were
      absent in 1 percent of the cases (one of 89). A mean of 1.9 sizable cutaneous
      vessels were identified. Musculocutaneous perforators were noted in 85 percent of
      cases and septocutaneous vessels were seen in 15 percent. Most septocutaneous
      vessels were located in the proximal thigh. In the midpoint of the thigh,
      musculocutaneous perforators predominate. Those located within 1 cm of the septum
      characteristically have a short, direct intramuscular course. In contrast, those
      located more laterally and distally in the thigh characteristically have a
      tortuous intramuscular course. An oblique branch of the lateral circumflex
      femoral artery was noted to be present in 35 percent of cases (31 of 88), and the
      dominant perforator supplying the anterolateral thigh was noted to originate from
      this branch in 14 percent of cases (12 of 88). CONCLUSIONS: This study further
      clarified the vascular pedicle anatomy of the anterolateral thigh. The existence
      of the oblique branch of the lateral circumflex femoral artery in a proportion of
      patients and its reliability when used as the flap pedicle were demonstrated.

PMID- 19182616
TI  - The free gracilis perforator flap: anatomical study and clinical refinements of a
      new perforator flap.
AB  - BACKGROUND: The free gracilis perforator flap is a fascioadipocutaneous flap on
      the medial thigh, based on perforators of the main pedicle of the gracilis
      myocutaneous flap. METHODS: An anatomical study was performed using 43 cadaver
      dissections. The vascular anatomy of the gracilis perforator flap with regard to
      myocutaneous and septocutaneous perforators was assessed. Clinical application
      was demonstrated in 14 cases. RESULTS: Musculocutaneous perforators of the
      gracilis muscle pedicle were present in all dissections and were 0.5 mm or more
      in 93 percent. Septocutaneous perforators were found in 84 percent of the
      dissections, and perforators of 0.5 mm or more were found in 63 percent. Most
      musculocutaneous perforators were found in the anterior quarter of the muscle
      where the pedicle enters the gracilis muscle. A constant intramuscular
      anastomosis between the main and second vascular pedicles of the gracilis was
      demonstrated that allowed design of an extended gracilis perforator flap.
      CONCLUSIONS: Successful clinical application in 14 cases confirmed vascular
      reliability. The gracilis perforator flap is a pliable, thin flap from the medial
      thigh that can be as large as 18 x 15 cm. The donor site is inconspicuous, and a
      functional gracilis muscle is preserved. By including a constant intramuscular
      anastomosis, it is possible to extend the territory of the free flap distally up
      to a length of 27 cm. Indications include reconstruction of cutaneous defects
      such as unstable scars or contractures. The medial thigh adipose tissue
      correlates well with the body mass index and thus can be used for breast
      reconstruction as a second choice if an abdominal perforator flap is not
      available.

PMID- 19182617
TI  - Negative-pressure wound therapy I: the paradox of negative-pressure wound
      therapy.
AB  - BACKGROUND: Does negative-pressure wound therapy reduce or increase the pressure
      of wound tissues? This seemingly obvious question has never been addressed by a
      study on living tissues. The aim of this study was to evaluate the nature of
      tissue pressure changes in relation to negative-pressure wound therapy. METHODS:
      Three negative-pressure wound therapy dressing configurations were evaluated
      circumferential, noncircumferential, and those within a cavity-on 15 human
      wounds, with five wounds in each category. Tissue pressure changes were recorded
      (using a strain gauge sensor) for each 75-mmHg increment in suction, up to -450
      mmHg. In the circumferential and noncircumferential groups, tissue pressure was
      also measured over a 48-hour period at a set suction pressure of -125 mmHg (n =
      10). RESULTS: In all three groups, mean tissue pressure increased proportionately
      to the amount of suction applied (p < 0.0005). Mean tissue pressure increments
      resulting from the circumferential dressings were significantly higher than those
      resulting from the noncircumferential (p < 0.0005) or cavity group (p < 0.0005);
      however, there was no significant difference between the latter two groups (p =
      0.269). Over the 48-hour period, there was a significant mean reduction in the
      (increased) tissue pressure (p < 0.04 for circumferential and p < 0.0005 for
      noncircumferential), but in only three of 10 cases did this reduce to pressures
      less than those before dressing application. CONCLUSIONS: Negative-pressure wound
      therapy increases tissue pressure proportionately to the amount of suction,
      although this becomes less pronounced over 48 hours. This suggests that negative
      pressure wound therapy dressings should be used with caution on tissues with
      compromised perfusion, particularly when they are circumferential.

PMID- 19182619
TI  - Negative-pressure wound therapy II: negative-pressure wound therapy and increased
      perfusion. Just an illusion?
AB  - BACKGROUND: A recent study demonstrated that negative-pressure wound therapy
      increases underlying tissue pressure. This finding is incongruous with studies
      using laser Doppler that show that perfusion is immediately increased on
      initiation of suction. This study investigated perfusion in negative-pressure
      wound therapy using two alternative modalities. METHODS: Radioisotope perfusion
      imaging was used to determine perfusion beneath circumferential negative-pressure
      wound therapy dressings on 20 healthy hands (n = 20). Ten hands received suction
      pressures of -400 mmHg and 10 received -125 mmHg, with the contralateral hand
      used as a control without any suction. Transcutaneous partial pressure of oxygen
      was used to determine perfusion beneath noncircumferential negative-pressure
      wound therapy dressings on 12 healthy legs (n = 12), with each volunteer being
      sequentially randomized to receive suction pressures of -400 and -125 mmHg,
      respectively. RESULTS: Tissues undergoing circumferential negative-pressure wound
      therapy demonstrated a mean reduction in perfusion of 40 +/- 11.5 percent (p <
      0.0005) and 17 +/- 8.9 percent (p < 0.0005) at suction pressures of -400 mmHg and
      -125 mmHg, respectively. Perfusion reduction at -400 mmHg was significantly
      greater than at -125 mmHg (p < 0.015). In the noncircumferential negative
      pressure wound therapy group, there was a mean reduction in transcutaneous
      partial pressure of oxygen of 7.35 +/- 7.4 mmHg (p < 0.0005) and 5.10 +/- 7.4
      mmHg (p < 0.0005) at suction pressures of -400 mmHg and -125 mmHg, respectively.
      There was a tendency for greater reductions in the -400 mmHg group, but this was
      not significantly different from the -125 mmHg group (p = 0.07). CONCLUSIONS:
      These findings demonstrate that perfusion beneath negative-pressure wound therapy
      decreases for increasing suction pressure. Thus, it is suggested that negative
      pressure wound therapy should be used with caution on tissues with compromised
      vascularity, particularly when used circumferentially.

PMID- 19182620
TI  - Myofascial compartments of the hand in relation to compartment syndrome: a
      cadaveric study.
AB  - BACKGROUND: Acute compartment syndrome of the hand is an emergency requiring
      prompt surgical decompression. This cadaveric study aims to identify the
      myofascial compartments of the hand by detailed dissection and direct
      visualization, to provide an accurate anatomical basis for surgical
      decompression. METHODS: Fourteen fresh-frozen cadaveric hands were dissected. The
      findings were recorded by still digital photography. RESULTS: There was no well
      defined tough fascia overlying the thenar muscles, the hypothenar muscles, or the
      adductor pollicis. Areolar tissue was present between the individual thenar and
      hypothenar muscles. A distinct band of fascia was noted over the entire length of
      the ulnar three dorsal interosseous muscles. A band of fascia was noted over the
      distal portion of the palmar interossei but not over the proximal aspect. The
      above findings were found in all 14 specimens. A layer of loose areolar tissue
      was noted over the dorsal aspect of the first web space in eight specimens,
      whereas a distinct band of fascia was noted overlying the first dorsal
      interosseous muscle in the remaining six. CONCLUSIONS: This study has shown that
      no distinct tough fascia surrounded any of the intrinsic muscles of the hand
      completely. The thin filmy fascia partially encasing some of the muscles is
      unlikely to contribute to development of compartment syndrome. It is postulated
      that the unyielding overlying skin may serve as a constricting layer in addition
      to the fascia and contribute to raised intracompartmental pressures.

PMID- 19182621
TI  - Anatomical repair of zone 1 flexor tendon injuries.
AB  - BACKGROUND: Repair and rehabilitation of the flexor digitorum profundus tendon in
      zone I may be demanding. The aim of the authors' study was to assess a new
      technique for reinsertion of the distal flexor digitorum profundus tendon.
      METHODS: The authors' series consisted of 18 patients who required primary (n =
      10) or secondary (n = 8) repair of the flexor digitorum profundus tendon in zone
      I. A half-Bruner incision was extended into the distal volar skin to expose the
      insertion site. Two drill holes were made through the base of the distal phalanx
      obliquely from the insertion of the profundus tendon in a dorsolateral direction.
      A modified Kessler suture was passed through the tendon and then through these
      holes and tied anteriorly, providing transosseous, internal fixation. Range of
      movement was assessed according to Moiemen's categories. RESULTS: Fourteen
      patients had excellent or good results, two patients had fair results, and one
      patient had a poor result. One patient failed to complete physiotherapy and was
      lost to follow-up. No tendon rupture was documented during a mean follow-up
      period of 8 months. CONCLUSIONS: The authors' technique anchors the flexor
      digitorum profundus tendon or the graft in an anatomical position on the distal
      phalanx, without the need for external sutures or additional incisions.
      Furthermore, this is accomplished with minimal morbidity to the surrounding
      highly specialized tissue. The authors' results compare favorably with those of
      other techniques in the literature.

PMID- 19182622
TI  - Wide-awake flexor tendon repair.

PMID- 19182623
TI  - Documentation of the incidents associated with mandibular distraction:
      introduction of a new stratification system.
AB  - BACKGROUND: This article aims to assess the spectrum of unfavorable events or
      incidents encountered during mandibular distraction and to evaluate the
      difference in the incident rates among the following treatment groups: (1) native
      bone distraction using an external device, (2) native bone distraction using an
      internal device, and (3) grafted bone distraction using an external device.
      METHODS: This retrospective study examined the records of 141 patients treated by
      mandibular distraction over a 16-year period. Of the total 141 patients, 56
      underwent unilateral mandibular distraction and 85 underwent bilateral mandibular
      distraction, contributing to a total of 226 sided distraction procedures. The
      number of procedures performed on native bone using external devices was 149,
      versus 41 internal devices. There were 36 distractions performed on grafted bone
      with external devices. Incidents were broadly classified into three groups based
      on a severity index. A minor incident was one that resolved satisfactorily with
      minimal or no invasive intervention. A moderate incident was one that resolved
      satisfactorily with moderate clinical intervention. A major incident was one that
      did not resolve or could not be resolved with surgical intervention, and
      compromised treatment outcome. RESULTS: The major incident rate was 5.31 percent
      (total of 226 distraction procedures). A higher rate of major incidents was
      observed when distracting grafted bone. The overall minor incident rate was 26.99
      percent and the moderate incident rate was 20.35 percent. CONCLUSION: Mandibular
      distraction can be considered a safe and predictable procedure for
      lengthening/augmenting the mandible in patients with lower jaw deficiencies.

PMID- 19182624
TI  - Single sutural craniosynostoses: surgical outcomes and long-term growth.
AB  - BACKGROUND: This study was designed to examine long-term skull growth following
      single sutural synostosis corrections and to evaluate surgical outcomes. METHODS:
      A retrospective outcome assessment of all children treated with a single-stage,
      open-remodeling procedure for sagittal, metopic, unilateral coronal, and
      unilateral lambdoid synostosis was performed. Long-term growth was assessed from
      serial anthropometric measurements taken up to 11 years postoperatively (mean, 4
      years). RESULTS: Of 296 consecutive patients, complete records were available for
      248 operative procedures. The mean surgical age was 12.3 months (range, 2.5
      months to 8 years), with 36 patients older than 12 months. Transfusion rates
      decreased from 81 to 19 percent following the institution of blood conservation
      strategies. The average hospitalization was 2.5 days. There was one nonsurgically
      treated infection (0.4 percent), and no major complications or deaths. Five
      patients underwent secondary remodeling procedures (2 percent). Serial
      anthropometric measurements, obtained in 75 patients, showed normalization of
      cranial indices 6 weeks postoperatively, but subsequent measurements revealed
      statistically significant diminished growth. Earlier surgical treatment of
      metopic synostosis (4 months) was associated with significantly more growth
      inhibition than seen in those treated at an older age (12 months), with the other
      synostoses showing similar tendencies. CONCLUSIONS: Treatment of single sutural
      synostosis was extremely safe with very low reoperative rates, but subsequent
      calvarial growth was abnormal, with a tendency toward recapitulation of the
      primary deformity. Growth was less diminished in procedures performed in older
      infants. Surgeons treating single sutural craniosynostosis should consider
      expanding treatment goals beyond normalization to an overcorrection of the
      abnormal skull shape.

PMID- 19182625
TI  - The role of congenital muscular torticollis in the development of deformational
      plagiocephaly.
AB  - BACKGROUND: Numerous risk factors have been associated with the development of
      deformational plagiocephaly, although the etiology remains unclear. Torticollis
      and sternocleidomastoid imbalance are implicated, but reporting is variable. The
      authors sought to determine the incidence of torticollis/sternocleidomastoid
      imbalance in deformational plagiocephaly. METHODS: The authors prospectively
      evaluated 371 infants with cranial asymmetry between 2002 and 2003. Demographic
      data and medical history were recorded, and a questionnaire was administered.
      Cranial asymmetry and head rotation were assessed, and variables were
      statistically analyzed. RESULTS: Two-hundred two patients were included. Mean age
      at initial evaluation was 6.1 months (range, 3 to 16 months). Sixty-eight percent
      (n = 138) were male; 74 percent (n = 149) were flat on the right occiput; 14
      percent (n = 28) were from a multiple pregnancy (24 twins, four triplets); 27
      percent (n = 54) were premature; and four percent (n = 8) were syndromic. Ninety
      three percent (n = 188) of parents did not notice flattening at birth. Ninety-two
      percent (n = 186) recalled a preferential head position after birth, and in 95
      percent of these infants (n = 177 of 186) this improved with age. Only 24 percent
      (n = 48) of infants had been previously diagnosed or treated for torticollis.
      Mean cranial asymmetry was 12.5 mm (range, 8 to 25 mm). Ninety-seven percent (n =
      195) of infants had head rotational asymmetry of 15 degrees or greater, with more
      rotation to the flat side. The mean rotational difference was 24 degrees (range 0
      to 60; SD 9.8). There was a negative correlation (p = 0.004) between age and head
      rotational asymmetry (i.e., younger patients exhibited greater asymmetry) and a
      positive correlation (p = 0.043) between cranial asymmetry and head rotational
      asymmetry. CONCLUSIONS: The incidence of torticollis/sternocleidomastoid
      imbalance in deformational plagiocephaly is underreported. Because this condition
      improves rapidly during early infancy, the findings may be subtle and evidenced
      only by a history of preferential head rotation. The major cause of deformational
      plagiocephaly is limited head mobility in early infancy secondary to cervical
      imbalance.

PMID- 19182626
TI  - Craniomaxillofacial fibrous dysplasia: conservative treatment or radical surgery?
      A retrospective study on 68 patients.
AB  - BACKGROUND: Fibrous dysplasia is a benign bone lesion characterized by
      replacement of normal bone with fibro-osseous connective tissue. The surgical
      treatment of fibrous dysplasia is based on one of two different approaches,
      conservative or radical. METHODS: From January of 1980 to December of 2002, 95
      patients with fibrous dysplasia located in the craniomaxillofacial area presented
      to the authors' department. Twenty-one had the polyostotic type (22 percent), two
      had McCune-Albright syndrome (2 percent), and 72 had the monostotic type (76
      percent). Of 95 patients, 68 underwent surgery; the remaining 27 refused. Among
      the 68 patients who underwent surgery, 61 had radical excision, six received
      conservative treatment, and a patient with mandibular involvement received
      radical excision and immediate reconstruction with a free fibula flap after a
      recurrence experienced 2 years after primary remodeling surgery RESULTS: No
      disease recurrence was observed in cases treated with complete excision, whereas
      a case of mandibular involvement treated with remodeling required further
      surgery. Infection, resolved with antibiotics, was seen in one case, and palatal
      fistula was seen in two cases. In one case with cranial base involvement
      liquorrhea was observed. CONCLUSIONS: In most cases of monostotic or monofocal
      fibrous dysplasia of the craniofacial region, modern surgical techniques allow an
      aggressive but definitive treatment with good functional and aesthetic results.
      The authors perform radical treatment even in cases involving the maxilla and
      mandible, and prefer a conservative approach only in polyostotic cases and McCune
      Albright syndrome.

PMID- 19182627
TI  - Correction of frontonasoethmoidal encephalocele: the HULA procedure.
AB  - BACKGROUND: The frontonasoethmoidal encephalomeningocele deformity involves
      central herniation of a glial mass that "pushes outward" and deforms the medial
      orbit, medial canthus, nasomaxillary process, and nasal structures without
      resulting in hypertelorbitism. The authors studied a modification of the "Chula"
      repair, called the HULA procedure (H = hard-tissue sealant, U = undermine and
      excise encephalocele, L = lower supraorbital bar, A = augment nasal dorsum),
      which provided complete correction of the midline hard and soft-tissue structures
      using an intracranial and extracranial approach. METHODS: Filipino patients with
      frontonasoethmoidal encephalomeningoceles were treated by a civilian/military
      humanitarian team at Tripler Army Hospital (n = 12). Operative technique followed
      the four steps of the HULA frontoethmoidal encephalocele procedure. Postoperative
      and follow-up assessments were based on examination, photographic images,
      computed tomography scans, parental surveys, Whitaker score, and developmental
      testing. RESULTS: Patient ages ranged from 5 to 12 years; 67 percent were female
      and 33 percent male. Sixty-seven percent required excisions of poor-quality,
      hyperpigmented skin along with the large glial mass; the other 33 percent had a
      "closed" resection of the smaller mass through a gingivobuccal sulcus incision.
      No patients manifested cerebrospinal fluid leaks, infection, or elevated
      intracranial pressures postoperatively. Skeletal correction showed improved
      medial orbit distance, with a mean correction of 14 mm (42 percent). Whitaker
      score was 1.3 (no or minor soft-tissue revision necessary). Parental survey
      showed a high degree of satisfaction with the aesthetic and functional outcomes.
      Follow-up developmental tests showed normal global evaluations for all but one
      child with normal memory and attention skills. CONCLUSION: The authors' outcomes
      demonstrated that the HULA technique was a safe and effective approach for the
      complete correction of frontonasoethmoidal encephalomeningoceles.

PMID- 19182628
TI  - Gridplan midfacial analysis for alloplastic implants at the time of jaw surgery.
AB  - BACKGROUND: Middle-third facial implants are primarily indicated for facial
      plastic surgery and orthognathic surgery as well as the secondary treatment of
      facial trauma and congenital malformations. Several methods of clinical analysis
      have been described both for defect classification and for surgical technique and
      implant materials. These prove very difficult to apply so as to establish a
      precise standard. METHODS: A new frontal-view facial analysis was developed on
      the basis of a grid of three vertical and five horizontal lines, divided in turn
      into six high and four lower middle-third areas with three vertical lines on side
      view. These vertical lines (LC and P) prove useful for the purposes of
      quantifying degree of defect. The lines can be marked on the patient's face
      during the intraoperative phase so as to ensure correct implant placement. Medpor
      implants were applied and secured by means of circumvestibular incision during Le
      Fort I osteotomy with titanium miniscrews. RESULTS: One hundred fifty-one
      patients with zygomatic defects were treated by means of this method during the
      correction of facial malocclusion. The results were achieved as planned during
      the preoperative phase in all cases. Postoperative complications were of minor
      severity, and only one implant was removed. CONCLUSIONS: This method of facial
      analysis is simple, and the drawing of lines proves useful to ensure correct
      implant positioning and symmetry during the surgical phase. In addition to being
      very easy to apply, position, and shape, Medpor implants also offer long-term
      stability and involve no any major complications.

PMID- 19182629
TI  - Massive hemorrhage in facial fracture patients: definition, incidence, and
      management.
AB  - BACKGROUND: Significant hemorrhage from fractures of the midface is a recognized
      phenomenon, but because it is an uncommon occurrence, there is little in the
      literature to guide management of these patients. METHODS: The authors performed
      a retrospective study of life-threatening hemorrhage in facial fracture patients
      attending the Royal Adelaide Hospital over 20 years and report four recent cases.
      RESULTS: The incidence of massive hemorrhage was found to be 0.33 percent of
      patients with fracture of the midface or skull base over the 20 years before 2004
      and 1.7 percent in the subsequent year. Of the 19 patients identified from case
      notes and recent experience, seven died. In terms of management of hemorrhage,
      three patients had packing alone, 10 had balloon catheters inserted, and five had
      ligation of a vessel. Most patients had multiple other injuries, including six
      patients with head injuries. The mean number of units of packed red cells
      transfused was 9.5 (median, 7.5). In five of the cases identified, there was a
      delay in recognizing that facial fractures were the major source of hemorrhage.
      CONCLUSIONS: Massive hemorrhage from facial fractures is an underrecognized and
      inconsistently managed phenomenon. Although low in incidence, its timely
      recognition and better management may reduce the high mortality rate in this
      group of patients.

PMID- 19182630
TI  - Optimizing miniplate fixation for simple mandibular fractures.
AB  - SUMMARY: Optimal management of the mandible fracture is directly dependent on
      thorough evaluation, correct injury assessment, and timely initiation of
      appropriate therapy. As the mandible is a complex three-dimensional bone,
      significant structural differences in mandibular regions must be appreciated.
      While the small cross-section of the mandibular condyle imparts a particular
      vulnerability to injury, fractures of the angle, body, or symphyseal regions are
      associated with greater force and the potential for more complex injury. In
      conjunction with their video presentation, the authors discuss their approach to
      miniplate fixation of a symphyseal fracture.

PMID- 19182631
TI  - Vascularized membranes determine the anatomical boundaries of the subcutaneous
      fat compartments.
AB  - PURPOSE: The subcutaneous tissue of the human body has been described as being
      arranged in anatomical units or compartments. Distinct compartments have now been
      identified on the face, trunk, and extremities. Septal boundaries have been noted
      on histologic evaluation. Despite these observations, a unifying explanation for
      the compartmentalization of adipose tissue has not been presented. METHODS:
      Twenty hemifacial cadaver specimens were obtained from the University of Texas
      Southwestern Willed Body Program. In 10 hemifaces, latex injection of the common
      carotid arteries was performed in conjunction with dye injection of fat to
      identify perforator vessels and source vessels associated with each compartment.
      The radiologic characteristics of the vascular network were further evaluated in
      10 additional hemifaces using three-dimensional computed tomographic scanning. A
      lead oxide/gelatin mixture was injected into the common carotid arteries, and
      iodinated contrast was injected directly into the fat compartment. RESULTS: The
      perforator blood supply to the skin runs with, and is stabilized by,
      condensations of fascia. Each anatomical compartment evaluated in this study was
      associated with an identifiable artery or vein. Three-dimensional computed
      tomography after intravenous contrast injection confirmed the arrangement of
      perforator vessels running in the septal boundaries of each subcutaneous fat
      compartment. CONCLUSIONS: The subcutaneous tissue of the human body is
      partitioned by fibrous membranes that carry the perforator blood supply to the
      skin. Each anatomical compartment studied has an identifiable vessel that runs
      along its boundary. This interlocking connective tissue network provides
      stability and protection for the vascular supply to the face during facial
      animation. The anatomical arrangement of the subcutaneous tissues of the face and
      their associated vasculature is therefore highly organized, and could be related
      to the embryologic development of the facial musculature. This anatomical
      construct is applicable to the adipofascial tissues throughout the human body.

PMID- 19182632
TI  - Face lift with reposition malarplasty.
AB  - BACKGROUND: The malar highlight should be considered when performing face lifts
      in the midface area to restore young and attractive facial contour. The young,
      attractive face has malar highlights in the superior portion and a malar fat pad
      that provides fullness in the zygomatic area. Actually effective facial
      rejuvenation cannot be achieved by simply tightening soft tissue, especially in
      patients with a wide and descending mala. Furthermore, in patients with wide
      faces and a strong malar eminence, a face lift alone tends to make the face look
      wider. Therefore, the authors combined face lift with repositioning malarplasty
      to change the facial skeleton. METHODS: From March of 1989 to February of 2005,
      the authors performed malar repositioning to a more attractive position (usually
      superiorly and medially) and a simultaneous subperiosteal midface lift and
      forehead lift in 96 patients with aging faces and prominent, wide malar
      complexes. The subcutaneous face lift with superficial musculoaponeurotic system
      procedure has been added as a standard procedure for patients with lower face and
      neck problems. RESULTS: Postoperatively, malar highlights were moved to a more
      attractive position, and all patients were satisfied with their results. No
      serious complications, such as facial nerve injury or flap necrosis, were
      reported. CONCLUSION: Reposition malarplasty and face lift in combination proved
      to be an effective, long-lasting, and satisfactory method of facial rejuvenation,
      especially in patients with wide faces and a strong malar eminence.

PMID- 19182633
TI  - Nasal base reduction by alar release: a laboratory evaluation.
AB  - BACKGROUND: When reducing the broad nasal base, there is a limit to the amount of
      soft tissue that can be resected, beyond which the anatomy distorts and the
      nostrils become stenotic (if resection enters the nostril). Alar mobilization by
      freeing soft-tissue attachments helps. This study purported to examine the nature
      of those attachments and the extent of medialization. METHODS: The supporting
      tissues of the ala were sequentially divided in 16 fresh hemifacial cadavers. Key
      structures included the following: (1) the soft tissues and pyriform ligament of
      the anterior maxilla, (2) the periosteum posterior to the pyriform rim (in the
      bony nasal vault), and (3) the soft tissues along the horizontal pyriform rim.
      After release of each tethering region, the ala-pyriform distance was measured.
      RESULTS: After releasing the anterior maxillary periosteum and pyriform ligament
      along the vertical pyriform rim, the ala-pyriform distance was reduced by a mean
      of 1.9 mm. After releasing the periosteum posterior to the pyriform rim (in the
      nasal vault), it was reduced by a mean of 1.7 mm. Releasing the soft tissues
      (which were thick medially) of the horizontal pyriform rim reduced the mean
      distance 1.0 mm for a total of 4.6 mm. Medialization resulting from anterior and
      posterior releases was significantly greater than that from the horizontal
      pyriform rim (p < 0.0006 and p < 0.015, respectively), but they were not
      significantly different from one another. CONCLUSIONS: This cadaver study
      confirmed the role of the stabilizing effect of the pyriform ligament and the
      periosteum lateral and posterior to the pyriform rim. The total release was
      substantial, suggesting a clinical means of achieving tension-free alar
      medialization.

PMID- 19182634
TI  - Nasal base reduction: a treatment algorithm including alar release with
      medialization.
AB  - BACKGROUND: The broad nasal base is occasionally not correctable by excisional
      procedures alone because nostril distortion or stenosis may result (if resection
      enters the vestibule). Moreover, recurrence is a common problem when alar
      mobilization and suture approximation techniques are used. The authors developed
      an algorithm for nasal base reduction to prevent these complications. METHODS: A
      new classification of the broad nasal base was utilized that included patients
      with general nasal base enlargement and patients with a vertically oriented alar
      axis (traditionally difficult to correct without distortion). Both groups
      received an alar release including the following: (1) the soft tissues and
      pyriform ligament of the anterior maxilla; (2) the periosteum posterior to the
      pyriform rim (in the bony nasal vault); and (3) when necessary, soft tissues
      along the horizontal pyriform rim. Interalar sutures maintained the alae in their
      new medialized position. Twelve patients who only underwent alar release were
      evaluated. RESULTS: Nasal base reduction was achieved in all cases without
      distortion. Three patients required release of the horizontal tissues of the
      pyriform rim (including a condensation of the pyriform ligament). After a follow
      up period of 11 months to 3(3/4) years, there were two cases of partial
      recurrence and one partial airway obstruction. CONCLUSIONS: Not all causes of a
      broad nasal base are amenable to resection procedures, especially the generally
      broad nasal base such as that due to thick skin or a vertically oriented alar
      axis. However, a tension-free alar release with medialization by suture fixation
      is effective. The incidence of recurrence can be expected to be reduced.

PMID- 19182635
TI  - Advances in extensor tendon diagnosis and therapy.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Identify clinical situations in which hand sonography can result in the
      detection of partial extensor tendon tears. 2. Identify the limitations of
      magnetic resonance imaging in diagnosing extensor tendon tears. 3. Understand the
      various postoperative therapeutic protocols for extensor tendon repair. 4. Choose
      the appropriate surgical repair and postoperative therapeutic protocol for a
      specific extensor tendon injury. 5. Identify the social and economic variables
      that may influence the availability and efficacy of the various postoperative
      therapeutic protocols. BACKGROUND: This article describes how the application of
      radiographic imaging facilitates the earlier detection and differentiation of
      extensor tendon injuries. Furthermore, it defines the best surgical procedure and
      postoperative therapy for a specific injury. METHODS: A literature review was
      performed of extensor tendon injury articles published since 1989. RESULTS: High
      resolution sonography was more accurate than physical examination and magnetic
      resonance imaging in detecting extensor tendon injuries. Traditional
      postoperative static splinting was equivalent to early motion protocols for all
      uncomplicated thumb injuries and zone 1 to 3 injuries of the second through fifth
      digits. The only definable benefit of early motion therapy compared with static
      splinting was a quicker return to final function for proximal zones of injury in
      the second through fifth digits. The results of early active and passive motion,
      measured at 6 months, were comparable to those from static splinting. A higher
      rupture rate for early active motion and greater cost for early active and
      passive motion were noted compared with static splinting. CONCLUSIONS: High
      resolution sonography allows identification of difficult to diagnose partial and
      complete extensor tendon injuries. Static splinting should remain the
      postoperative standard of care for extensor tendon injuries to the thumb and
      distal zones of injury for digits 2 through 5. The best therapy protocol for
      proximal zones of injury should be individualized based on social and economic
      variables.

PMID- 19182636
TI  - Simulation in plastic surgery training and education: the path forward.
AB  - SUMMARY: Computer-based training simulators have been used extensively, most
      notably in flight simulation. Over the past 20 years, surgical simulators have
      been developed, initially for training of minimally invasive surgery and more
      recently for open surgical simulation. The key effort in today's surgical
      simulation field is to develop metrics to evaluate how well the skills learned in
      a simulator translate to improvement in real surgical skills, execution of
      procedures, and team cooperation in the operating room. The American College of
      Surgeons has begun implementing a phased approach to introduce simulation in
      training and education for general surgery. The authors believe that a similar
      training plan should be mandated for plastic surgery, to take advantage of the
      use of computers, virtual reality, and simulation in the training of plastic
      surgery residents and to explore the value of this technology for continuing
      medical education and maintenance of certification. This article gives a brief
      background and history of surgical simulation and its technology, followed by a
      detailed description of the three phases of the American College of Surgeons'
      plan and how the authors propose that each phase be implemented, with
      modifications as applicable for trainees in plastic surgery.

PMID- 19182639
TI  - Leadership trends in plastic surgery.
AB  - BACKGROUND: The authors examined the recent trends in the composition,
      appointment, and turnover of chairpersons in academic plastic surgery. METHODS: A
      survey regarding the characteristics of the current and former department
      chairpersons in plastic surgery was mailed to the 89 existing academic plastic
      surgery programs. The survey focused on the age, gender, subspecialty, interim
      tenure, and overall tenure of the two groups. RESULTS: An initial response was
      received from 60 chairpersons. The majority of current chairpersons are male (81
      of 89, 91 percent), which is slightly lower than the group of immediate past
      chairs, of whom 98 percent (87 of 89) were male. From the questionnaires, it was
      noted that for both the current and former groups of chairpersons, the 40- to 50
      year age range was the most frequent age group at which an individual was
      appointed to that position. Approximately one-third (35.7 percent) of the current
      group consider themselves "general plastic surgeons." This differs from their
      predecessors, of whom 56.0 percent reported the same designation. An increase in
      the promotion of existing faculty to chairpersons was also noted. As compared
      with 44.2 percent of the previous group, 69.5 percent of the current chairpersons
      were promoted from within the department. CONCLUSIONS: The population of academic
      chairpersons in plastic surgery is changing. Today, more chairpersons appear to
      be younger and specialty trained. Examining the history of academic leadership
      and identifying trends in any field of medicine can only help to better prepare
      the specialty for the future.

PMID- 19182638
TI  - Measuring quality of surgical care: is it attainable?
AB  - SUMMARY: Healthcare quality has emerged as an important discussion topic for the
      American people. With the continued lack of health insurance coverage for over 15
      percent of Americans, questions are being posed regarding why the United States
      has spent $2.1 trillion per year in healthcare and is still unable to provide the
      highest quality of healthcare in the world. The World Health Organization's 2000
      World Health Report ranked the United States at 24 out of 191 member countries in
      healthcare indices. Because of a looming reduction in the number of Americans
      covered through the Medicare and Medicaid programs due to budgetary constraints,
      many initiatives have been proposed to cut the cost of healthcare and at the same
      time improve the quality of the American system. In this article, the authors
      summarize the history of these quality initiatives and discuss current and future
      directions of programs to achieve better healthcare for the country. They also
      discuss how the American Society of Plastic Surgeons is engaging national
      organizations to be part of the solution for this crisis.

PMID- 19182640
TI  - Transatlantic innovations: new frontiers in plastic surgery.

PMID- 19182641
TI  - What is a leader?

PMID- 19182645
TI  - Potential impacts of nutritional deficiency of postbariatric patients on body
      contouring surgery (invited discussion).

PMID- 19182647
TI  - The paramedian forehead flap: a dynamic anatomical vascular supply verifying
      safety and clinical implications.

PMID- 19182649
TI  - The Sabattini-Abbe flap: a historical note.

PMID- 19182651
TI  - Lethal pulmonary embolisms are avoidable.

PMID- 19182652
TI  - Bariplastic surgery: the Cleveland clinic Florida experience.

PMID- 19182656
TI  - Plastic Surgery Research Council supplement.

PMID- 19182657
TI  - The Plastic Surgery Research Council supplement.

PMID- 19182659
TI  - Sequential limb ischemia demonstrates remote postconditioning protection of
      murine skeletal muscle.
AB  - BACKGROUND: Ischemic postconditioning, the process of exposing tissues to brief
      cycles of ischemia-reperfusion after critical ischemia, can mitigate local
      ischemia-reperfusion injury. Remote protection of skeletal muscle has never been
      demonstrated in postconditioning models of ischemia-reperfusion injury. METHODS:
      Mice were subjected to 2 hours of ipsilateral hind limb ischemia followed by
      reperfusion. Contralateral limb ischemia was subsequently induced for 2 hours
      after either 0 (n = 6), 20 (n = 6), or 120 (n = 5) minutes of ipsilateral limb
      reperfusion. These groups were compared with animals subjected to bilateral
      simultaneous injury (n = 8) and sham animals that did not undergo ischemia (n =
      6). The gastrocnemius muscles were harvested for histologic evaluation, and
      injury was recorded as the percentage of injured fibers. RESULTS: The first limbs
      undergoing injury in the 20-minute interval group had a 59 percent injury
      reduction compared with contralateral limbs (16.0 +/- 2.4 percent versus 39.5 +/-
      6.5 percent) after 24 hours of reperfusion and 62 percent reduction after 48
      hours (24.4 +/- 3.0 percent versus 63.6 +/- 5.5 percent). In animals with no
      interval or a 120-minute interval between the onset of limb ischemia, there was
      no significant difference in injury between hind limbs. The injury in these
      groups was similar to that in hind limbs subjected to simultaneous bilateral
      ischemia. CONCLUSIONS: A 20-minute reperfusion interval between hind limb
      ischemia significantly protects against injury in the initially ischemic limb,
      while similar injury is observed with simultaneous ischemia or an interval of 120
      minutes. This study demonstrates remote postconditioning of skeletal muscle and
      may lead to the development of post hoc therapies.

PMID- 19182660
TI  - Daily topical tacrolimus therapy prevents skin rejection in a rodent hind limb
      allograft model.
AB  - BACKGROUND: Skin is the most immunogenic component of a composite tissue
      allograft. Topical immunotherapy is an attractive therapeutic modality with which
      to provide local immunosuppression, with minimal systemic toxicity. The present
      study was performed to investigate the potential of topical tacrolimus to prolong
      survival of the skin component of a composite tissue allograft. METHODS: Wistar
      Furth-to-Lewis rat orthotopic hind limb transplants were performed. Group I
      consisted of rats treated with topical tacrolimus; group II, antilymphocyte serum
      plus 21 days cyclosporine; and group III, antilymphocyte serum plus 21 days of
      cyclosporine plus topical tacrolimus. In group IV, tacrolimus levels in blood,
      skin, and muscle were measured in an autograft control group. RESULTS: All
      animals in group I (n = 8) developed grade III clinical rejection by
      postoperative day 9. In group II (n = 9), the median onset of grade III rejection
      was postoperative day 40 (range, postoperative days 34 to 44). In group III (n =
      6), two animals developed focal grade III rejection on postoperative days 35 and
      56. The remaining four animals reached the 100-day endpoint without grade III
      rejection. In group IV, tacrolimus levels were low or undetectable in blood,
      whereas skin levels were 100-fold higher than underlying muscle. CONCLUSIONS:
      Topical tacrolimus therapy has the potential to prevent skin rejection in a
      composite tissue allograft. Preoperative depletion of T cells with antilymphocyte
      serum, along with a short course of systemic immunosuppression, prevents acute
      rejection, whereas topical tacrolimus inhibits immune cell function in the skin.
      Concentrations of tacrolimus are substantially higher in skin compared with
      underlying muscle and peripheral blood. Topical immunotherapy could reduce the
      morbidity associated with systemic immunosuppression in clinical composite tissue
      allografts.

PMID- 19182661
TI  - A model for functional recovery and cortical reintegration after hemifacial
      composite tissue allotransplantation.
AB  - BACKGROUND: The ability to achieve optimal functional recovery is important in
      both face and hand transplantation. The purpose of this study was to develop a
      functional rat hemifacial transplant model optimal for studying both functional
      outcome and cortical reintegration in composite tissue allotransplantation.
      METHODS: Five syngeneic transplants with motor and sensory nerve appositions
      (group 1) and five syngeneic transplants without nerve appositions (group 2) were
      performed. Five allogeneic transplants were performed with motor and sensory
      nerve appositions (group 3). Lewis (RT1) rats were used for syngeneic transplants
      and Brown-Norway (RT1) donors and Lewis (RT1) recipients were used for allogeneic
      transplants. Allografts received cyclosporine A monotherapy. Functional recovery
      was assessed by recordings of nerve conduction velocity and cortical neural
      activity evoked by facial nerve and sensory (tactile) stimuli, respectively.
      RESULTS: All animals in groups 1 and 3 showed evidence of motor function return
      on nerve conduction testing, whereas animals in group 2, which did not have nerve
      appositions, did not show electrical activity on electromyographic analysis (p <
      0.001). All animals in groups 1 and 3 showed evidence of reafferentation on
      recording from the somatosensory cortex after whisker stimulation. Animals in
      group 2 did not show a cortical response on stimulation of the whiskers (p <
      0.001). CONCLUSION: The authors have established a hemiface transplant model in
      the rat that has several modalities for the comprehensive study of motor and
      sensory recovery and cortical reintegration after composite tissue
      allotransplantation.

PMID- 19182662
TI  - Maintenance of donor-specific chimerism despite osteopontin-associated bone
      fibrosis in a vascularized bone marrow transplantation model.
AB  - BACKGROUND: The role of vascularized bone allografting is not established in
      plastic and reconstructive surgery. The authors evaluated the contribution by
      osteopontin to fibrosis of allografted bone in a vascularized bone marrow
      transplantation model across a major histocompatibility complex barrier. METHODS:
      Thirty-six transplantations were performed between Brown Norway (RT1 n) donors
      and Lewis (RT1 l) recipients divided into three groups: group 1, isografts
      between Lewis rats (n = 12); group 2, allografts without treatment (n = 8); and
      group 3, allografts under a 7-day alphabeta-T-cell receptor/cyclosporine protocol
      (n = 16). Flow cytometry assessed the presence of chimerism for donor major
      histocompatibility complex class I (RT1 n) antigens. Immunostaining was used to
      determine osteopontin expression in grafted and recipient bone, and histologic
      examination was used to assess bone architecture. RESULTS: Early engraftment of
      donor bone marrow cells (RT1 n) into the recipient bone marrow compartment was
      achieved at posttransplantation day 7. This corresponded with osteopontin
      expression restricted to the endosteum of trabecular bone and was associated with
      the preservation of hematopoietic cells within donor bone. Cell migration between
      donor and recipient bone marrow compartments was confirmed by the presence of
      recipient cells (RT1 l) within the allografted bone and donor-origin cells (RT1
      n) within the recipient bone. At posttransplantation day 63, osteopontin
      expression within allografted bone was associated with allograft bone fibrosis
      and lack of hematopoietic properties. In contrast, the recipient's contralateral
      bone demonstrated a highly localized osteopontin expression pattern within the
      endosteum and active hematopoiesis with the presence of donor-specific (RT1 n)
      cells and correlated with chimerism maintenance. CONCLUSIONS: These results
      confirm that despite up-regulation of osteopontin expression and fibrosis of
      allografted bone, vascularized bone marrow transplantation resulted in efficient
      engraftment of donor cells into the recipient's bone marrow compartment, leading
      to chimerism maintenance.

PMID- 19182664
TI  - Adipose stromal cells and platelet-rich plasma therapies synergistically increase
      revascularization during wound healing.
AB  - BACKGROUND: The authors examined the efficacy of adipose stem cells, when
      supplied either alone or in platelet-rich fibrin gels, to improve wound healing.
      METHODS: A porcine full-thickness wound model was used to compare six topical
      treatments: platelet-poor plasma; platelet-rich plasma; autologous adipose stem
      cells plus platelet-poor plasma; autologous adipose stem cells plus platelet-rich
      plasma; allogeneic adipose stem cells containing green fluorescent protein plus
      platelet-poor plasma; and saline (control). One week after isolation, adipose
      stem cells were applied to full-thickness wounds on the paraspinal and thoracic
      regions of three pigs (44 wounds per pig; each treatment was applied to eight
      separate wounds). Each wound was monitored over 21 days for closure, cosmesis,
      and histopathology. RESULTS: There was no significant difference in the
      reepithelialization rate, but treatments containing adipose stem cells
      demonstrated increased microvessel densities (31.75 +/- 5.73 vessels/cm2 versus
      7.93 +/- 3.61 vessels/cm2) compared with groups without adipose stem cells. Wound
      cosmesis was improved in the adipose stem cell plus platelet-rich plasma group
      compared with other treatment groups (p < 0.05). Vascular endothelial growth
      factor levels detected in matrices containing adipose stem cells were
      approximately 7-fold higher compared with platelet-rich plasma or platelet-poor
      plasma (p < 0.05). Localization of transgenic green fluorescent protein plus
      adipose stem cells indicated incorporation near neovasculature. CONCLUSIONS: In
      normal healing wounds, adipose stem cells appear to enhance the healing process
      only when provided in a fibrin gel vehicle containing a number of complementary
      wound-healing trophic factors. Perivascular adipose stem cell localization
      suggests a function in enhancing blood supply through providing physical and
      paracrine support to newly forming vessels.

PMID- 19182663
TI  - Mesenchymal stem cells can participate in ischemic neovascularization.
AB  - BACKGROUND: Cells from the bone marrow contribute to ischemic neovascularization,
      but the identity of these cells remains unclear. The authors identify mesenchymal
      stem cells as a bone marrow-derived progenitor population that is able to engraft
      into peripheral tissue in response to ischemia. METHODS: A murine model of skin
      ischemia was used. Bone marrow, blood, and skin were harvested at different time
      points and subjected to flow cytometric analysis for mesenchymal and
      hematopoietic markers (n = 3 to 7 per time point). Using a parabiotic model
      pairing donor green fluorescent protein (GFP)-positive with recipient wild-type
      mice, progenitor cell engraftment was examined in ischemic tissue by fluorescence
      microscopy, and engrafted cells were analyzed by flow cytometry for endothelial
      and mesenchymal markers. In vitro, the ability of both bone marrow- and adipose
      derived mesenchymal stem cells to adopt endothelial characteristics was examined
      by analyzing (1) the ability of mesenchymal stem cells to take up DiI-acetylated
      low-density lipoprotein and Alexa Fluor lectin, and (2) phenotypic changes of
      mesenchymal stem cells co-cultured with GFP-labeled endothelial cells or under
      hypoxic/vascular endothelial growth factor stimulation. RESULTS: In vivo, the
      bone marrow mesenchymal stem cell population decreased significantly immediately
      after surgery, with subsequent engraftment of these cells in ischemic tissue.
      Engrafted cells lacked the panhematopoietic antigen CD45, consistent with a
      mesenchymal origin. In vitro, bone marrow- and adipose-derived mesenchymal stem
      cells took up DiI-acetylated low-density lipoprotein and Alexa Fluor lectin, and
      expressed endothelial markers under hypoxic conditions. CONCLUSIONS: The authors'
      data suggest that mesenchymal precursor cells can give rise to endothelial
      progenitors. Consequently, cell-based therapies augmenting the mesenchymal stem
      cell population could represent powerful alternatives to current therapies for
      ischemic vascular disease.

PMID- 19182665
TI  - SDF-1 alpha expression during wound healing in the aged is HIF dependent.
AB  - BACKGROUND: Age-related impairments in wound healing are associated with
      decreased neovascularization, a process that is regulated by hypoxia-responsive
      cytokines, including stromal cell-derived factor (SDF)-1 alpha. Interleukin-1
      beta is an important inflammatory cytokine involved in wound healing and is
      believed to regulate SDF-1 alpha expression independent of hypoxia signaling.
      Thus, the authors examined the relative importance of interleukin (IL)-1 beta and
      hypoxia-inducible factor (HIF)-1 alpha on SDF-1 alpha expression in aged wound
      healing. METHODS: Young and aged mice (n = 4 per group) were examined for wound
      healing using a murine excisional wound model. Wounds were harvested at days 0,
      1, 3, 5, and 7 for histologic analysis, immunohistochemistry, enzyme-linked
      immunosorbent assay, and Western blot. An engineered wild-type and mutated SDF
      luciferase reporter construct were used to determine HIF transactivation.
      RESULTS: Aged mice demonstrated significantly impaired wound healing, reduced
      granulation tissue, and increased epithelial gap compared with young controls.
      Real-time polymerase chain reaction demonstrated reduced SDF-1 alpha levels in
      aged wounds that correlated with reduced CD31+ neovessels. Western blots revealed
      decreased HIF-1 alpha protein in aged wounds. However, both IL-1 beta and
      macrophage infiltrate were unchanged between young and aged animals. Using the
      wild-type and mutated SDF luciferase reporter construct in which the hypoxia
      response element was deleted, only young fibroblasts were able to respond to IL-1
      beta stimulation, and this response was abrogated by mutating the HIF-binding
      sites. This suggests that HIF binding is essential for SDF-1 transactivation in
      response to both inflammatory and hypoxic stimuli. CONCLUSIONS: SDF-1 alpha
      deficiency observed during aged wound healing is attributable predominantly to
      decreased HIF-1 alpha levels rather than impaired IL-1 beta expression.

PMID- 19182666
TI  - A novel method for targeted gene therapy in ischemic tissues through viral
      transfection of an expression cassette containing multiple repetitions of hypoxia
      response element.
AB  - BACKGROUND: Increased levels of the transcription factor hypoxia inducible factor
      (HIF)-1 occur only in hypoxic tissue. The authors propose a therapeutic strategy
      that relies on HIF-1, the enhancer hypoxia response element (HRE), and the
      delivery vector adeno-associated virus-2 (AAV2) to direct ischemia specific gene
      therapy to skin. METHODS: An expression cassette containing the CMV promoter
      driving the reporter gene green fluorescent protein (GFP) was used to assess
      cutaneous tropism of AAV2. Transfection of dermal fibroblasts and immortalized
      keratinocytes (HaCat) was assessed with flow cytometry. Human embryonic kidney
      293 (HEK) cells were used to produce vector stocks and test the authors'
      therapeutic strategy in quadruplicate. An expression cassette with nine repeats
      of HRE linked to beta-galactosidase (LacZ) within the AAV2 vector was
      constructed. HEK cells were transfected and exposed to normoxic (21% oxygen) and
      hypoxic (1% oxygen) conditions. LacZ activity was measured by conversion of
      galactoside red-beta-D-galactopyranoside. RESULTS: Approximately 50 percent of
      dermal fibroblasts and HaCat cells were transfected when treated with 1 x 10(4)
      genome copies/cell of AAV2-CMV-GFP. Using the same titration of AAV2-9HRE-LacZ,
      transfected HEK cells demonstrated LacZ activity of 0.496 +/- 0.068 U/microg in
      normoxia and 2.9 +/- 0.58 U/microg in hypoxia. Transfected cells exposed to 24
      hours of hypoxia show greater than an 11-fold increase in LacZ activity (p <
      0.05) compared with baseline normoxic controls. CONCLUSIONS: The authors' results
      confirm that AAV2 has in vitro tropism for skin-derived cell lines. Furthermore,
      HRE will drive gene expression in ischemia but not normoxia. This is the first
      step toward the authors' goal of HIF-1-regulated gene therapy to prevent ischemia
      related skin injury.

PMID- 19182667
TI  - Tensile strain-induced Ets-2 phosphorylation by CaMKII and the homeostasis of
      cranial sutures.
AB  - BACKGROUND: Mechanotransduction underpins the homeostasis of musculoskeletal
      tissues, including cranial sutures. Intracellular calcium, [Ca 2+]ic, and protein
      phosphorylation are two intermediate variables in signal relay during
      mechanotransduction. This project establishes a chain of cause and effect,
      linking cellular strain to substrate phosphorylation, and identifies the agent
      and target sites of phosphorylation. METHODS: Cyclic tensile force (0.5 N at 1
      Hz) was applied to 1-day-old rat sagittal sutures. [Ca 2+]ic was measured by FURA
      2. Ets-2 phosphorylation by CaMKII was tested using Western blot autoradiography.
      Peptide array was constructed to determine the precise sites of phosphorylation.
      The results were confirmed with mass spectroscopy and Western blots using phospho
      specific antibodies. RESULTS: [Ca 2+]ic increased rapidly in response to tensile
      stress. In the presence of Ca2+, CaMKII caused Ets-2 phosphorylation. Of the
      three possible sites for phosphorylation of Ets-2 by CaMKII, RVPS, FESF, RLSS,
      Serine 246, 310, and 313 were the targets. Furthermore, the contiguous sequence
      modified this effect. Mass spectroscopy showed 80 Da (molecular weight of
      phosphate group, -PO3) right shifts consistent with phosphorylation. There was
      cytosolic translocation of Ets-2 on tensile deformation of suture cells. CaMKII
      binding of Ets-2 occurred within 30 minutes after the onset of tensile strain.
      CONCLUSIONS: Cranial suture cells can respond to tensile forces by increasing [Ca
      2+]ic, which causes CaMKII to phosphorylate Ets-2, thus altering Ets-2 binding to
      its downstream promoters. Of note, Ets-2 is at the intersection of three key
      pathways important in craniosynostosis: fibroblast growth factor-2, transforming
      growth factor-beta, and mechanotransduction.

PMID- 19182668
TI  - Ex vivo Noggin gene therapy inhibits bone formation in a mouse model of
      postoperative resynostosis.
AB  - BACKGROUND: Resynostosis following surgical correction of primary
      craniosynostosis necessitates further surgical intervention, thereby increasing
      morbidity and mortality. Bone morphogenetic proteins are known to be expressed
      during normal bone healing. This study tested the hypothesis that treatment of
      suturectomy sites with Noggin, an extracellular antagonist of bone morphogenetic
      proteins, would inhibit postoperative resynostosis in a mouse suturectomy model.
      METHODS: Healing of small interfrontal suturectomies was assessed in three groups
      of mice using radiographic, micro-computed tomographic, and histologic analyses.
      The groups were as follows: group 1, no treatment (n = 36); group 2, green
      fluorescent protein (GFP)-labeled cells in a collagen scaffold (n = 36); and
      group 3, Noggin/GFP-expressing cells in a collagen scaffold (n = 36). RESULTS:
      Radiographic analysis of defect area showed that Noggin-treated suturectomy sites
      were significantly larger than untreated sites 4 and 8 weeks postoperatively (p <
      0.05). Analysis of defect volume showed that Noggin-treated defects were
      significantly larger than untreated defects at all time points after surgery. The
      GFP-treated defects demonstrated some inhibition of bone formation, but this
      inhibition was not significant compared with untreated controls 12 weeks after
      surgery. CONCLUSIONS: These findings suggest that Noggin is an effective
      inhibitor of bone formation within small suturectomy sites and that Noggin may be
      useful in avoiding postoperative resynostosis. Noggin treatment may be useful as
      an adjunct to traditional surgical intervention for the treatment of children
      with craniosynostosis.

PMID- 19182669
TI  - Radioprotection of osteoblasts by a fractionated dose regimen and amifostine.
AB  - BACKGROUND: Radioprotective modalities such as dose fractionation and
      pharmacologic agents such as amifostine have been used to protect bone and other
      types of normal tissue from the damaging effects of ionizing radiation without
      significantly impacting tumor kill. To better understand the cellular mechanism
      of radioprotection of osseous tissue, the authors sought to determine the effect
      of dose fractionation and amifostine on isolated osteoblasts. METHODS: Isolated
      primary rat calvarial osteoblasts were exposed to single or fractionated doses of
      ionizing radiation both with and without amifostine pretreatment. Endpoints
      included cell growth (n = 4), vascular endothelial growth factor production as
      measured by enzyme-linked immunosorbent assay (n = 3), and early
      osteodifferentiation as measured by a quantitative alkaline phosphatase assay (n
      = 3). RESULTS: Both dose fractionation and amifostine protect osteoblasts from
      the growth inhibitory effects of ionizing radiation. Fractionation but not
      amifostine was protective for hypoxia-induced vascular endothelial growth factor
      production (used as a surrogate marker of normal osteoblast function). Neither
      fractionation nor amifostine could prevent the inhibitory effect of ionizing
      radiation on normal osteoblast osteodifferentiation as measured by alkaline
      phosphatase production. CONCLUSIONS: Both dose fractionation and amifostine have
      valid roles as radioprotectants for osteoblasts and can act in an additive
      fashion. Radioprotection of cell growth and viability does not necessarily
      correlate with preservation of normal cellular function. Combination protocols
      involving dose fractionation and amifostine may be effective in radioprotection
      of osteoblasts and normal osseous tissue.

PMID- 19182670
TI  - Biomechanical assessment of regenerate integrity in irradiated mandibular
      distraction osteogenesis.
AB  - BACKGROUND: The role of mandibular distraction osteogenesis for reconstructing
      mandibular defects following radiation therapy depends on the quality of
      attenuated bone healing in the regenerate. This study investigated the regenerate
      properties after radiation therapy using yield and breaking load. The authors
      hypothesized that both would be significantly reduced in mandibular distraction
      osteogenesis following radiation therapy compared with mandibular distraction
      osteogenesis alone. METHODS: Male Sprague-Dawley rats underwent left mandibular
      fractionated 36-Gy preoperative external beam radiation therapy and then 2 weeks
      of recovery (n = 7) or no radiation therapy (n = 10) before surgery. External
      fixators were secured and unilateral osteotomies were created behind the third
      molar, followed by 4 days of latency and then mandibular distraction
      osteogenesis: 0.3 mm every 12 hours for 8 days (5.1 mm) and 4 weeks of
      consolidation. Unoperated controls received no radiation therapy (n = 13).
      Mandibles were tension tested at 0.5 mm/second to failure, and yield and breaking
      load were determined. RESULTS: There was a significantly lower breaking load for
      mandibular distraction osteogenesis following radiation therapy compared with
      mandibular distraction osteogenesis, alone, but there was no significant
      difference in yield between the groups. Both groups had significantly lower
      breaking load and yield when compared with unoperated controls. CONCLUSIONS: The
      lowered breaking load in mandibular distraction osteogenesis following radiation
      therapy reflects the reduced biomechanical quality of the regenerate, despite
      evidence of radiographic union. These data show that radiographic union is not an
      adequate outcome measure for regenerate healing and support the need to define
      quantitative bone-healing metrics in mandibular distraction osteogenesis
      following radiation therapy before implementation in head and neck
      reconstruction.

PMID- 19182671
TI  - Real-time in vivo assessment of the nerve microenvironment with coherent anti
      Stokes Raman scattering microscopy.
AB  - BACKGROUND: Current analysis of nerve injury and repair relies largely on
      electrophysiologic and ex vivo histologic techniques. In vivo architectural
      assessment of a nerve without removal or destruction of the tissue would greatly
      assist in the grading of nerve injury and in the monitoring of nerve regeneration
      over time. Coherent anti-Stokes Raman scattering microscopy is an optical process
      with particular sensitivity for high-lipid-containing molecules such as myelin.
      This in vivo nonthermal technique offers high-resolution images that the authors
      aim to evaluate in both normal and injured nerves. METHODS: A demyelinating crush
      injury was reproduced in the sciatic nerves of Sprague-Dawley rats (n = 12).
      Animals were randomized into groups, and coherent anti-Stokes Raman scattering
      microscopy was undertaken at day 1 and weekly up to 4 weeks after injury.
      Functional analysis was undertaken weekly and histomorphometry was completed
      after imaging. RESULTS: All animals demonstrated loss of sciatic nerve function
      following injury. Recovery was documented, with functional data approaching
      normal at 3 and 4 weeks. Demyelination was confirmed in nerves up to 2 weeks
      after injury. Remyelination was observed in the 3-week group and beyond. Imaging
      of normal nerve revealed structured myelin bundles. These results were consistent
      with histologic findings that showed a statistically significant improvement in
      myelination over time. CONCLUSIONS: The authors conclude that coherent anti
      Stokes Raman scattering microscopy has the ability to image the peripheral nerve
      following demyelinating crush injury. This technology, which permits in vivo,
      real-time microscopy of nerves at a resolution of 5 mum, could provide invaluable
      diagnostic and prognostic information regarding intraneural preservation and
      recovery following injury.

PMID- 19182672
TI  - Ischemia-reperfusion-induced apoptotic endothelial cells isolated from rat
      skeletal muscle.
AB  - BACKGROUND: The purpose of the present study was to investigate ischemia
      reperfusion-induced apoptosis and necrosis in endothelial cells isolated from
      skeletal muscle. METHODS: A vascular pedicle isolated rat gracilis muscle model
      was used. After surgical preparation, clamps were applied to the vascular pedicle
      to create 4 hours of ischemia and released for reperfusion (ischemia-reperfusion
      group, n = 9). Clamping was omitted in sham ischemia-reperfusion rats (sham
      ischemia-reperfusion group, n = 9). The muscle samples were harvested after 20
      hours of reperfusion for the process of cell isolation. One hundred thousand
      cells from each sample were stained by monoclonal anti-CD146-fluorescein (a
      principal marker for mature endothelial cells), Annexin V-PE, or 7
      aminoactinomycin D to detect and quantify apoptotic and necrotic cells. Twenty
      thousand cells from each sample were scanned and analyzed by flow cytometry.
      RESULTS: The average +/- SEM of CD146-fluorescein-positive cells was 20.0 +/- 2.9
      percent, suggesting that these cells might be endothelial cells from the muscle
      microvasculature. In the population of gated CD146-fluorescein-positive cells,
      the average percentage of apoptotic cells (stained by Annexin V-PE) was 15.9 +/-
      2.2 percent in the sham ischemia-reperfusion group and 33.5 +/- 5.3 percent in
      the ischemia-reperfusion group (p < 0.01), the average percentage of
      necrotic/apoptotic cells (stained by both 7-aminoactinomycin D and Annexin V-PE)
      was 17.8 +/- 4.1 percent in the sham ischemia-reperfusion group and 39.2 +/- 3.1
      percent in the ischemia-reperfusion group (p < 0.01). CONCLUSIONS: Given the
      results of the present study, the authors hypothesize that the endothelial cells
      lining microscopic blood vessels are among the major contributors to ischemia
      reperfusion-induced cell apoptosis and necrosis detected from rat skeletal
      muscle.

PMID- 19182673
TI  - Embryonic stem cell-derived motor neurons form neuromuscular junctions in vitro
      and enhance motor functional recovery in vivo.
AB  - BACKGROUND: Transplantation of embryonic stem cell-derived motor neurons may
      support the biological integrity of denervated muscle by forming new
      neuromuscular junctions and up-regulating specific growth factors. The authors
      examined the functional properties of embryonic stem cell-derived motor neurons
      in vitro and the effect of these cells transplanted in vivo. METHODS: Murine
      GFP/HB9 embryonic stem cells were differentiated into motor neurons. Co-cultures
      of motor neurons and myotubes were prepared to confirm the formation of
      neuromuscular junctions with synaptic markers. Athymic mice (n = 59) were
      assigned randomly to one of three experimental groups. A tibial nerve transection
      was performed without nerve repair, and motor neurons were transplanted into the
      gastrocnemius muscles immediately after transection (n = 24) or 3 weeks after
      denervation (n = 24). Quantitative and histologic assessments of gastrocnemius
      muscle were performed at days 7 and 21 after cell transplantation. Additional
      experimental groups (n = 11), where the tibial nerve underwent repair after
      transplantation, were formed. The effect of the transplants on motor recovery
      following nerve repair was investigated. RESULTS: Co-culture experiments showed
      the formation of neuromuscular junctions. In the experiment with nerve
      transection without nerve repair, the muscles transplanted with motor neurons
      were less atrophied than control phosphate-buffered saline-injected muscles at
      days 7 and 21. Those muscles receiving cells transplanted 3 weeks after
      denervation were not preserved. The motor recovery after nerve repair with cell
      transplantation was significantly enhanced compared with the control group.
      CONCLUSIONS: Transplantation of motor neurons prevented denervation atrophy but
      was not capable of rescuing already atrophied muscle. After nerve repair, motor
      neuron transplantation improved functional recovery.

PMID- 19182674
TI  - Accelerating stem cell proliferation by down-regulation of cell cycle regulator
      p21.
AB  - BACKGROUND: Tissue engineering is often limited by the time required for culture
      expansion of cells necessary for scaffold seeding. Cell cycle regulators control
      entry and exit into the cell cycle and as such regulate cellular proliferation
      rates. The authors hypothesized that transient alteration in cell cycle
      regulators can be utilized as a means to accelerate stem cell proliferation.
      METHODS: Mesenchymal stem cells were harvested from wild-type mice and mice
      deficient in the cell cycle regulator p21. Wild-type cells were treated with
      small interfering RNA against p21 in two- or three-dimensional cultures in vitro.
      Cellular proliferation and the potential for cellular differentiation into the
      bone or fat lineage were assessed. RESULTS: Mesenchymal stem cells treated with
      small interfering RNA targeting p21 demonstrated a significant decrease in p21
      protein and mRNA expression 96 hours after treatment. They also proliferated
      significantly faster than control cells (2.5 to three times) in both two- and
      three-dimensional culture. Similarly, cells harvested from p21-deficient mice
      demonstrated a significant acceleration in cellular proliferation. Inhibition of
      p21 expression was not associated with significant changes in spontaneous
      cellular differentiation. However, transient p21 inhibition promoted both
      osteoblastic and adipogenic differentiation when cells were exposed to
      differentiation medium. CONCLUSIONS: Transient inhibition of the cell cycle
      regulator p21 results in significant acceleration of mesenchymal stem cell
      proliferation without promoting spontaneous cellular differentiation. Exposure to
      differentiation medium results in increased cellular differentiation toward the
      osteoblast and fat lineage. Manipulation of cell cycle regulators may represent a
      novel means by which stem cell proliferation can be accelerated, thereby
      decreasing the time required for scaffold synthesis in tissue engineering.

PMID- 19182675
TI  - BMP-2 does not influence the osteogenic fate of human adipose-derived stem cells.
AB  - BACKGROUND: Recent studies have shown that bone morphogenetic protein (BMP)-2, a
      potent osteogenic growth factor, in combination with human adipose-derived stem
      cells can heal critical-sized bony defects. However, whether BMP-2 induces an
      osteogenic response in the adipose-derived stem cells remains unknown. METHODS: :
      In vitro calcium production, osteogenic gene expression, and BMP-2 receptor
      expression on the adipose-derived stem cell surface were analyzed in BMP-2
      stimulated adipose-derived stem cells. The cells (2 x 10(7) cells) maintained in
      osteogenic medium were treated with an initial pulse of BMP-2 for 48 hours or 7
      days or were given continuous BMP-2. To assess the response of these cells to BMP
      2 in vivo, they (250,000 cells) were seeded into polylactic-co-glycolic acid
      (PLGA) collagraft scaffolds treated with 5 microg of BMP-2 and implanted into
      critical-sized femoral rat defects (n = 40). Healing was assessed histologically
      and quantitated by micro-computed tomography. RESULTS: In vitro treatment of
      adipose-derived stem cells with BMP-2 revealed decreased ability of the cells to
      undergo matrix calcification, demonstrated by decreased calcium production and
      decreased osteogenic gene expression of transcription factor Cbfa-1 and key
      extracellular proteins. Flow cytometry demonstrated decreased expression of BMP-2
      receptors 1a and 1b in osteogenically differentiated adipose-derived stem cells
      stimulated with BMP-2. In vivo implantation of adipose-derived stem cell-seeded
      PLGA did not result in healing of critical-sized femoral defects in rodents,
      whereas implantation of BMP-2-absorbed PLGA, with or without adipose-derived stem
      cells, consistently healed these defects. CONCLUSIONS: The data suggests that
      osteogenic differentiation of adipose-derived stem cells is marginally affected
      by the addition of BMP-2. Consequently, stem cells in combination with BMP-2 may
      not be a viable strategy for the bony healing.

PMID- 19182676
TI  - Estimation of the current global burden of cryptococcal meningitis among persons
      living with HIV/AIDS.
AB  - OBJECTIVE: Cryptococcal meningitis is one of the most important HIV-related
      opportunistic infections, especially in the developing world. In order to help
      develop global strategies and priorities for prevention and treatment, it is
      important to estimate the burden of cryptococcal meningitis. DESIGN: Global
      burden of disease estimation using published studies. METHODS: We used the median
      incidence rate of available studies in a geographic region to estimate the region
      specific cryptococcal meningitis incidence; this was multiplied by the 2007
      United Nations Programme on HIV/AIDS HIV population estimate for each region to
      estimate cryptococcal meningitis cases. To estimate deaths, we assumed a 9% 3
      month case-fatality rate among high-income regions, a 55% rate among low-income
      and middle-income regions, and a 70% rate in sub-Saharan Africa, based on studies
      published in these areas and expert opinion. RESULTS: Published incidence ranged
      from 0.04 to 12% per year among persons with HIV. Sub-Saharan Africa had the
      highest yearly burden estimate (median incidence 3.2%, 720 000 cases; range, 144
      000-1.3 million). Median incidence was lowest in Western and Central Europe and
      Oceania (</=0.1% each). Globally, approximately 957 900 cases (range, 371 700-1
      544 000) of cryptococcal meningitis occur each year, resulting in 624 700 deaths
      (range, 125 000-1 124 900) by 3 months after infection. CONCLUSION: This study,
      the first attempt to estimate the global burden of cryptococcal meningitis, finds
      the number of cases and deaths to be very high, with most occurring in sub
      Saharan Africa. Further work is needed to better define the scope of the problem
      and track the epidemiology of this infection, in order to prioritize prevention,
      diagnosis, and treatment strategies.

PMID- 19182677
TI  - Refusal bias in HIV prevalence estimates from nationally representative
      seroprevalence surveys.
AB  - OBJECTIVES: To assess the relationship between prior knowledge of one's HIV
      status and the likelihood to refuse HIV testing in populations-based surveys and
      explore its potential for producing bias in HIV prevalence estimates. METHODS:
      Using longitudinal survey data from Malawi, we estimate the relationship between
      prior knowledge of HIV-positive status and subsequent refusal of an HIV test. We
      use that parameter to develop a heuristic model of refusal bias that is applied
      to six Demographic and Health Surveys, in which refusal by HIV status is not
      observed. The model only adjusts for refusal bias conditional on a completed
      interview. RESULTS: Ecologically, HIV prevalence, prior testing rates and refusal
      for HIV testing are highly correlated. Malawian data further suggest that amongst
      individuals who know their status, HIV-positive individuals are 4.62 (95%
      confidence interval, 2.60-8.21) times more likely to refuse testing than HIV
      negative ones. On the basis of that parameter and other inputs from the
      Demographic and Health Surveys, our model predicts downward bias in national HIV
      prevalence estimates ranging from 1.5% (95% confidence interval, 0.7-2.9) for
      Senegal to 13.3% (95% confidence interval, 7.2-19.6) for Malawi. In absolute
      terms, bias in HIV prevalence estimates is negligible for Senegal but 1.6 (95%
      confidence interval, 0.8-2.3) percentage points for Malawi. Downward bias is more
      severe in urban populations. Because refusal rates are higher in men,
      seroprevalence surveys also tend to overestimate the female-to-male ratio of
      infections. CONCLUSION: Prior knowledge of HIV status informs decisions to
      participate in seroprevalence surveys. Informed refusals may produce bias in
      estimates of HIV prevalence and the sex ratio of infections.

PMID- 19182678
TI  - HIV seroconversion among injection drug users in detention, Tehran, Iran.
AB  - Jails may foster the spread of HIV, particularly among drug users. In 2006, male
      injection drug users (n = 499) detained in Tehran consented to HIV testing at
      intake and discharge. HIV prevalence at intake was 24.4%. Nine of those who were
      HIV negative at intake were positive at discharge (annualized incidence rate
      16.8%), including one p24 antigen positive. Jails may be contributing to the
      rapid spread of HIV in Iran and should be major points for prevention
      interventions.

PMID- 19182679
TI  - Infusional fluorouracil, epirubicin, and cisplatin followed by weekly paclitaxel
      plus bevacizumab in locally advanced breast cancer with unfavorable prognostic
      features.
AB  - The objective of this study was to evaluate the clinical and biological
      activities of bevacizumab in combination with preoperative anthracyclines and
      taxane-based chemotherapy in locally advanced breast cancer selected for
      unfavorable prognostic features. Patients with cT2-4c, cN0-2, estrogen and
      progesterone receptors less than 10% of the cells or cT4d and any
      estrogen/progesterone receptors expression received four courses of ECF
      chemotherapy (epirubicin, cisplatin, fluorouracil as continuous infusion)
      followed by three courses of weekly paclitaxel in combination with bevacizumab.
      Thirty patients were included in the study. An objective response, either
      complete or partial, was observed in 26 patients (87%; 95% confidence interval:
      69-96%), stable disease was observed in two patients (7%), and two patients (7%)
      progressed. A pathological complete response was obtained in 10 patients (33%;
      95% confidence interval: 17-53%). Side effects related to bevacizumab with grade
      >or=2 included headache and hypertension. A nonstatistical significant decrease
      in the median value of circulating endothelial cells was observed at surgery
      (3.0/microl vs. 5.7/microl, P=0.19). In conclusion, high rates of both clinical
      and pathological responses with anthracycline-containing chemotherapy followed by
      weekly paclitaxel plus bevacizumab were observed in locally advanced breast
      cancer with unfavorable prognostic features. A non-negligible rate of progressive
      disease was observed, suggesting careful monitoring of the patients. Further
      studies evaluating the potential benefit of bevacizumab in neoadjuvant treatment
      need to be tested.

PMID- 19182680
TI  - Clinical and surgical recurrence of Crohn's disease after ileocolonic resection
      in a specialist unit.
AB  - BACKGROUND: Postoperative clinical and endoscopic recurrence is common in Crohn's
      disease. AIM: We aimed to assess postoperative recurrence and management in a
      cross-sectional patient cohort in one specialist unit, before the introduction of
      a uniform postoperative preventive strategy. METHODS: Review of patients who had
      an ileocolonic resection for Crohn's disease between 2002 and 2005 in a secondary
      and tertiary care specialist centre. RESULTS: Ninety-nine patients (42 male; 57
      female; mean age, 37 years) with a median disease duration of 10 years, were
      reviewed. Indications for surgery were obstruction (n=61), failed medical therapy
      (n=31) and internal fistula(e) (n=7). Thirty patients (30%) were active smokers
      at the time of resection. Fifty patients (51%) had at least one previous Crohn's
      resection. Clinical and surgical recurrence rates were 28 and 5%, respectively,
      at 1 year. All five patients had the same indication for their further surgery as
      for their index operation (four fistulizing or stricturing). Median time to
      clinical recurrence was 10 months in those with recurrence. Nineteen percent of
      patients had an ileocolonoscopy at a median of 6 months after surgery, and 60%
      had been reviewed by a gastroenterologist, after surgery. Clinical recurrence
      occurred in nine of 28 (32%) without and 19 of 71 with (26%) postoperative
      medical therapy (P=NS). CONCLUSION: Postoperative recurrence of Crohn's disease
      was high in the short term. The indication for repeat surgery stayed true within
      patients. Prospective treatment strategies, based on recent trial evidence, are
      needed to diminish postoperative recurrence.

PMID- 19182681
TI  - Severe liver damage associated with celiac disease: findings in six toddler-aged
      girls.
AB  - OBJECTIVE: Light-to-moderate liver damage is often seen in children diagnosed
      with celiac disease, but severe liver damage is rarely observed. METHODS: During
      a 12-year-long period our center took care of six 13-36-month-old girls who
      developed severe liver damage 1-24 months after the diagnosis of celiac disease.
      RESULTS: Four girls had acute liver failure; two of them had to be liver
      transplanted. The other four girls recovered without transplantation and none of
      the six patients developed autoimmune disease during the 2-14-year-long follow-up
      period. Although adenovirus type 2 was found in the urine and stools of one girl,
      her liver histopathology did not resemble viral hepatitis. Certain autoimmune
      features could be observed initially in some of the children but finally none of
      them fulfilled the criteria for autoimmune liver disease and this pattern did not
      change during the several years of follow-up. Thorough investigation could not
      find any alternative pathogenetic cause and thus, the association with celiac
      disease is obvious. Histopathology showed various degrees of intralobular
      inflammation, necrosis, involvement of the small bile ducts, and in one case
      interface hepatitis; but in general, histopathology did not reveal a common
      pathogenetic mechanism. CONCLUSION: Although rare, severe hepatic damage or
      failure can develop in association with celiac disease. The etiology is varying
      and multifactorial. Consequently, children with newly onset celiac disease should
      be routinely checked for liver function and vice versa, children with severe
      liver damage should be investigated for untreated celiac disease.

PMID- 19182682
TI  - Predictors of long-term outcome of functional dyspepsia and duodenal ulcer after
      successful Helicobacter pylori eradication--a 7-year follow-up study.
AB  - AIMS: To investigate the course of dyspeptic symptoms, predictors of symptom
      relief and use of antidyspeptic drugs in patients with duodenal ulcer disease and
      functional dyspepsia 6-7 years after successful Helicobacter pylori eradication.
      PATIENTS AND METHODS: Patients with H. pylori-positive duodenal ulcer or
      functional dyspepsia, included in a prospective, randomized study from January
      1996 to June 1997, and successfully treated with standard triple therapy, were
      eligible. After 6-7 years, case histories of 142 patients were retrieved and
      patients were interviewed by telephone. They were asked about the presence of
      dyspeptic symptoms and health care needs during the last week and over the last 6
      7 years. Predictive factors of complete long-term relief of symptoms have been
      evaluated. RESULTS: Of the 114 eligible patients, 104 (49 with duodenal ulcer and
      55 with functional dyspepsia) were included in the study. The mean duration of
      follow up was 6.6+/-0.5 years. Complete relief of dyspeptic symptoms was
      reported, in this period, by 49.0% of duodenal ulcer patients and 36.4% of
      patients with functional dyspepsia (P=0.271). Persistence of symptoms within 3
      months of H. pylori eradication and female sex were predictive of persistence of
      symptoms in the following 6-7 years, in patients with functional dyspepsia. In
      turn, approximately 50% of the patients with complete symptom remission, within 6
      months of H. pylori eradication, later became symptomatic. Since the end of the
      H. pylori eradication trial, 26.9% of patients were still using or had used
      antidyspeptic drugs; patients with functional dyspepsia having used them more
      frequently than duodenal ulcer patients (36.4 vs. 16.3%; P=0.037). CONCLUSION: In
      clinical practice, long-term symptomatic benefit, in duodenal ulcer patients,
      after H. pylori eradication, is similar to that in patients with functional
      dyspepsia. Early evaluation of symptoms after successful H. pylori eradication
      may be predictive of outcome in dyspeptic patients. Most symptomatic patients did
      not seek antidyspeptic drugs. Use of antisecretory medications was, however,
      greater in patients with functional dyspepsia than in duodenal ulcer patients.

PMID- 19182683
TI  - Increased prevalence of left-handedness in hemifacial microsomia.
AB  - Ten percent of people are left handed, but a higher frequency has been associated
      with certain craniofacial malformations, such as cleft lip and unilateral coronal
      synostosis. The purpose of this study was to determine the frequency of left
      handedness in patients with hemifacial microsomia (HFM). Patients with HFM were
      identified in our craniofacial database. Normal controls were recruited by local
      pediatricians. Data gathered included age, sex, and handedness (determined by
      writing and/or drawing); the orbit, mandible, ear, nerve, and soft tissue (OMENS)
      plus score and side of involvement were tabulated for patients with HFM. Hand
      preference was compared between the groups using chi analysis; possible
      correlations were analyzed between handedness and age, sex, the OMENS score,
      extracraniofacial findings, and side of involvement. One hundred seventy-eight
      patients with HFM were identified; 92 (51%) were excluded. Of the 86 included,
      48% were boys (n = 47) and the mean age at inquiry was 13.5 years. Predominant
      side of involvement was right in 49% (n = 42) and left in 38% (n = 33). Eleven
      patients (13%) had severe involvement of both sides. Expanded-spectrum HFM was
      documented in 41% of patients. Ninety-six children were in the control group; 44%
      were boys (n = 42), and the mean age was 10 years. The difference in age between
      the groups was significant (P < 0.05), but sex differences were not. Patients
      with HFM were more likely to be left handed for writing compared with the control
      group (26% vs. 11%; P < 0.05). The frequency was higher, 36%, in those with
      bilateral involvement (P > 0.05). There was no correlation with predominant side
      or OMENS score. This study confirms that this disorder affects cerebral
      lateralization.

PMID- 19182684
TI  - Age-related changes of the upper airway assessed by 3-dimensional computed
      tomography.
AB  - The purposes of this study were to establish normative data for airway size and
      shape and to evaluate differences associated with age and sex using 3-dimensional
      (3-D) imaging. Patients being evaluated by computed tomography (CT) for
      pathologic conditions not related to the airway were included. Using 3-D Slicer
      (Harvard Surgical Planning Laboratory, Brigham and Women's Hospital, Boston, MA),
      a software program, digital 3-D CT reconstructions were made and parameters of
      airway size analyzed: volume (VOL), surface area (SA), length (L), mean cross
      sectional area (mean CSA), minimum retropalatal (RP), minimum retroglossal (RG),
      minimum cross-sectional area (min CSA), and lateral (LAT) and anteroposterior
      (AP) retroglossal airway dimensions. Evaluation of airway shape included LAT/AP
      and RP/RG ratios, uniformity (U), and sphericity, a measure of compactness (Psi).
      Children were stratified by stage of dentition: primary, 0 to 5 years; mixed, 6
      to 11 years; permanent, 12 to 16 years; and adults, older than 16 years.
      Differences in airway parameters by age and sex were analyzed. Forty-six CT scans
      (31 males) were evaluated. Adults had larger (VOL, SA, L, mean CSA, and LAT),
      more elliptical (increased LAT/AP, P = 0.01), less uniform (U, P = 0.02), and
      less compact (decreased Psi, P = 0.001) airways than children. Among children,
      those in the permanent dentition demonstrated greater VOL (P < 0.01), SA (P <
      0.01), L (P < 0.01), and mean CSA (P < 0.01) than those in the primary dentition.
      There were no gender differences in airway parameters. Understanding differences
      in 3-D airway size and morphology by age may serve as a basis for evaluation of
      patients with obstructive sleep apnea and may help to predict and to evaluate
      outcomes of treatment.

PMID- 19182685
TI  - Sturge-Weber syndrome: soft-tissue and skeletal overgrowth.
AB  - Sturge-Weber syndrome (SWS) is characterized by capillary malformation, glaucoma,
      leptomeningeal vascular anomalies, and variable facial overgrowth. The purpose of
      this study was to document the prevalence and morbidity of facial hypertrophy in
      2 cohorts: group 1, surveyed patients registered in the SWS Foundation, and group
      2, patients treated at our Vascular Anomalies Center. Predictive variables
      included age, sex, region of capillary stain, and ocular or cerebral involvement.
      Outcome variables were soft-tissue and bony overgrowth, as well as the type of
      operative correction. In group 1, the response rate to our questionnaire was
      29.3% (108/368). Facial overgrowth was documented in 60.0% of patients. Soft
      tissue hypertrophy was present in 55.0%; the lip (81.0%) was the most commonly
      affected site. Skeletal hypertrophy was reported in 22% of patients; the maxilla
      (83.0%) was the most frequently overgrown bone. Overall, 23.0% of patients (36.5%
      with overgrowth) had an operation: 34.0% of patients with soft tissue hypertrophy
      and 9.0% with skeletal enlargement. In group 2, 47 patients with SWS were treated
      at our center: 83% had facial overgrowth, either a localized cutaneous lesion
      (18.0%), soft-tissue enlargement (70.0%), or bony hypertrophy (45.0%). As in
      group 1, the lip (75.0%) and maxilla (94.0%) were the most commonly enlarged
      structures. Operations were necessary for localized cutaneous lesions (86.0%),
      soft-tissue hypertrophy (53.0%), or skeletal overgrowth (11.0%). In conclusion,
      facial hypertrophy is a major component of SWS; these patients should be
      counseled about the risk of overgrowth and about the types of possible operative
      correction.

PMID- 19182686
TI  - Mandibular asymmetry and the fourth dimension.
AB  - This paper represents more than 30 years of discussion and collaboration with Drs
      Joseph Murray and John Mulliken in an attempt to understand growth patterns over
      time (ie, fourth dimension) in patients with hemifacial microsomia (HFM). This is
      essential for the development of rational treatment protocols for children and
      adults with jaw asymmetry. Traditionally, HFM was thought of as a unilateral
      deformity, but it was recognized that 20% to 30% of patients had bilateral
      abnormalities. However, early descriptions of skeletal correction addressed
      almost exclusively lengthening of the short (affected) side of the face. Based on
      longitudinal clinical observations of unoperated HFM patients, we hypothesized
      that abnormal mandibular growth is the earliest skeletal manifestation and that
      restricted growth of the mandible plays a pivotal role in progressive distortion
      of both the ipsilateral and contralateral facial skeleton. This hypothesis
      explains the progressive nature of the asymmetry in patients with HFM and
      provides the rationale for surgical lengthening of the mandible in children to
      prevent end-stage deformity. During the past 30 years, we have learned that this
      phenomenon of progressive distortion of the adjacent and contralateral facial
      skeleton occurs with other asymmetric mandibular undergrowth (tumor resection,
      radiation therapy, or posttraumatic defects) and overgrowth (mandibular condylar
      hyperplasia) conditions. In this paper, I describe the progression of deformity
      with time in patients with mandibular asymmetry as a result of undergrowth and
      overgrowth. Understanding these concepts is critical for the development of
      rational treatment protocols for adults with end-stage asymmetry and for children
      to minimize secondary deformity.

PMID- 19182688
TI  - Treatment of selective serotonin reuptake inhibitor-resistant depression in
      adolescents: predictors and moderators of treatment response.
AB  - OBJECTIVE: To advance knowledge regarding strategies for treating selective
      serotonin reuptake inhibitor (SSRI)-resistant depression in adolescents, we
      conducted a randomized controlled trial evaluating alternative treatment
      strategies. In primary analyses, cognitive-behavioral therapy (CBT) combined with
      medication change was associated with higher rates of positive response to short
      term (12-week) treatment than medication alone. This study examines predictors
      and moderators of treatment response, with the goal of informing efforts to match
      youths to optimal treatment strategies. METHOD: Youths who had not improved
      during an adequate SSRI trial (N = 334) were randomized to an alternative SSRI,
      an alternative SSRI plus CBT, venlafaxine, or venlafaxine plus CBT. Analyses
      examined predictors and moderators of treatment response. RESULTS: Less severe
      depression, less family conflict, and absence of nonsuicidal self-injurious
      behavior predicted better treatment response status. Significant moderators of
      response to CBT + medication (combined) treatment were number of comorbid
      disorders and abuse history; hopelessness was marginally significant. The
      CBT/combined treatment superiority over medication alone was more evident among
      youths who had more comorbid disorders (particularly attention
      deficit/hyperactivity disorder and anxiety disorders), no abuse history, and
      lower hopelessness. Further analyses revealed a stronger effect of combined CBT +
      medication treatment among youths who were older and white and had no nonsuicidal
      self-injurious behavior and longer prestudy pharmacotherapy. CONCLUSIONS:
      Combined treatment with CBT and antidepressant medication may be more
      advantageous for adolescents whose depression is comorbid with other disorders.
      Given the additional costs of adding CBT to medication, consideration of
      moderators in clinical decision making can contribute to a more personalized and
      effective approach to treatment.

PMID- 19182690
TI  - Physiological correlates of social avoidance behavior in children and adolescents
      with fragile x syndrome.
AB  - OBJECTIVE: To investigate whether eye-gaze avoidance, a striking phenotypic
      feature in fragile X syndrome (FXS), is associated with high levels of
      "hyperarousal" during social interactions with others. To date, almost all
      studies in this area have been confounded by inclusion of task demands in
      addition to social demands. METHOD: We monitored the cardiovascular activity and
      eye-gaze avoidance of 50 boys and girls with FXS aged 5 to 20 years during a 25
      minute intensive social interaction session with an unfamiliar experimenter. To
      control for possible family and genetic factors in cardiovascular activity, we
      compared each child with FXS with their same-sex typically developing biological
      sibling. RESULTS: Participants with FXS obtained significantly higher heart
      rates, lower vagal tone, and lower heart rate variability estimates both at
      baseline and during the social interaction session compared with their typically
      developing siblings. Although eye-gaze avoidance occurred at significantly higher
      levels in the children with FXS, this behavior decreased slightly over the course
      of the session (a "warm-up" effect) and did not seem to be associated with
      cardiovascular activity. In the girls with FXS, higher levels of the fragile X
      mental retardation protein were associated with higher (and more typical) heart
      rate variability. CONCLUSIONS: These data suggest that both sympathetic and
      parasympathetic nervous systems are dysregulated in FXS. However, given that
      prolonged exposure to social demands does not inevitably lead to increased
      anxiety or "hyperarousal," professionals should not be deterred from providing
      much needed social skills interventions for individuals with FXS.

PMID- 19182689
TI  - Neurocognitive function in pediatric bipolar disorder: 3-year follow-up shows
      cognitive development lagging behind healthy youths.
AB  - OBJECTIVE: Longitudinal follow-up of neurocognitive functioning in people with
      pediatric bipolar disorder (PBD) was conducted to characterize the developmental
      trajectory of cognitive disabilities in this disorder. METHOD: Patients with PBD
      (n = 26) and controls (HC; n = 17; mean age 11.66 +/- 2.70 years) completed
      cognitive testing at baseline and then again at a 3-year follow-up. Groups were
      matched at baseline on age, sex, race, parental socioeconomic status, general
      intelligence, and single-word reading ability. The PBD group received treatment
      guided by a standardized medication algorithm during the 3-year period. A battery
      of neuropsychological tests was administered to assess attention, executive
      function, working memory, verbal memory, visual memory, and visuospatial
      perception at baseline and follow-up. RESULTS: At baseline and follow-up, the
      patients showed deficits in all of the examined domains. At 3-year follow-up,
      developmental progress in executive functions and verbal memory was significantly
      less in the patients with PBD than in the HC. Improvement on attention, working
      memory, visual memory, and visuospatial perception tasks in the patients with PBD
      was comparable to that of the HC, but the patients with PBD remained impaired in
      all domains relative to the HC. CONCLUSIONS: The developmental delay in some
      neurocognitive functioning in PBD suggests that the illness disrupts cognitive
      development with potential lifelong implications for reduced functional ability.
      Treating bipolar symptoms does not seem to prevent the lag in cognitive
      development. This dysmaturation may be a direct effect of the illness on brain
      function, or it may represent indirect consequences of psychopathology or
      medications on cognitive development.

PMID- 19182691
TI  - Age variability in the association between heavy episodic drinking and adolescent
      suicide attempts: findings from a large-scale, school-based screening program.
AB  - OBJECTIVE: Alcohol use is a risk factor for suicidal behavior among adolescents,
      but it is not clear whether this association is consistent during the adolescent
      period. This study examined the age-specific associations between heavy episodic
      drinking (HED) and self-reported suicide attempts in a large and diverse sample
      of adolescents. METHOD: Screening data from 32,217 students, between the ages of
      11 and 19 years, in 225 schools were analyzed. Logistic regression analyses
      estimating the impact of HED on self-reported suicide attempts in the past year
      were performed. RESULTS: Heavy episodic drinking was significantly associated
      with self-reported suicide attempts (odds ratio 1.78, p <.05) controlling for
      depressive symptoms. However, there was substantial age variability in this
      association, with the association between HED and self-reported attempts stronger
      among younger adolescents. Among youths aged 13 years and younger, those who
      reported an episode of HED during the past year were roughly 2.6 times more
      likely to report an attempt than those who did not report HED in the past year,
      in contrast to 1.2 times among youths aged 18 years and older. CONCLUSIONS: Heavy
      episodic drinking is a clear risk factor for suicidal behavior among younger
      adolescents, beyond the risk conveyed by depressive symptoms. Further research
      investigating the bases for increased suicide risk among younger adolescents
      engaging in HED is warranted. Results provide support to AACAP's practice
      parameters calling for attention to substance abuse in the assessment of suicide
      risk and suggest that routine screening for HED by physicians may improve the
      detection of adolescent suicide risk, particularly among younger adolescents.

PMID- 19182693
TI  - Long-term impact of family arguments and physical violence on adult functioning
      at age 30 years: findings from the simmons longitudinal study.
AB  - OBJECTIVE: To prospectively examine the extent to which an increase in family
      arguments by age 15 years and the occurrence of family physical violence by age
      18 years are related to deficits in key domains of adult functioning at age 30
      years. METHOD: The 346 participants were part of a single-age cohort from a
      predominately white working-class community whose psychosocial development has
      been traced since age 5 years. Family arguments and violence were assessed
      through self-reports during adolescence. Developmentally relevant areas of
      current adult functioning were measured by self-reports, structured diagnostic
      interviews, and clinical interviewer ratings. RESULTS: Both family arguments and
      physical violence were significantly related to compromised functioning across
      multiple areas of adult functioning. Although many associations were somewhat
      attenuated after controlling for sex, other early family adversities, and family
      history of disorder, most relations retained statistical significance. Both risk
      factors were linked with later mental health problems and deficits in
      psychological and occupational/career functioning. Family violence was also
      linked to poorer physical health at age 30 years. CONCLUSIONS: Findings
      underscore the potential long-term impact of troubled family interactions and
      highlight the critical importance of early intervention programs for youths
      experiencing either verbal conflict or physical violence in the home.

PMID- 19182692
TI  - 12-month and lifetime prevalence of suicide attempts among black adolescents in
      the National Survey of American Life.
AB  - OBJECTIVE: Provide nationally representative data on the prevalence and
      psychiatric correlates of suicidal ideation and attempts among African American
      and Caribbean black adolescents in the United States. METHOD: Data on nonfatal
      suicidal behavior among 1,170 African American and Caribbean black adolescents
      aged 13 to 17 years are from the National Survey of American Life-Adolescent, a
      nationally representative household survey of adults with an attached adolescent
      sample conducted between February 2001 and June 2003. RESULTS: Nationwide black
      adolescents reported having a lifetime prevalence of 7.5% for suicidal ideation
      and 2.7% for attempts. The 12-month prevalence of suicidal ideation and attempt
      was 3.2% and 1.4%, respectively. Among all respondents, 4% of black American
      adolescents and 7% of female subjects were projected to attempt suicide by age 17
      years. African American adolescents were approximately five times more likely
      than Caribbean black adolescents to attempt suicide. Almost half of the National
      Survey of American Life-Adolescent respondents who reported a suicide attempt had
      never met criteria for any of the DSM-IV disorders by the time of their attempts.
      CONCLUSIONS: Clinicians should be trained to screen for suicidal behavior, even
      among those without DSM-IV disorders, when treating black adolescents,
      particularly female subjects. In addition, preventive efforts should consider
      ethnic differences in suicide risk and targeting nonclinical settings.

PMID- 19182694
TI  - Flaxseed combined with low-dose estrogen therapy preserves bone tissue in
      ovariectomized rats.
AB  - OBJECTIVE: Flaxseed is rich in lignans and alpha-linolenic acid, compounds that
      may promote healthy skeletons. Many postmenopausal women consume complementary
      health products such as flaxseed or its components in addition to pharmacological
      agents such as low-dose estrogen therapy for additional support for menopausal
      symptoms and related conditions. However, their combined effect on bone health is
      unknown. The aim of this study was to determine the effects of 10% dietary
      flaxseed, low-dose estrogen therapy, or their combination on bone mineral
      density, biomechanical strength, and skeletal fatty acid composition in an
      ovariectomized rat model of postmenopausal osteoporosis. METHODS: Ovariectomized
      rats received (1) basal diet (negative control), (2) 10% flaxseed, (3) low-dose
      estrogen implant (13 microg, 90 day release), or (4) flaxseed + low-dose estrogen
      implant for 12 weeks. A sham-operated group was included as a positive control.
      Bone mineral density, biomechanical strength, and fatty acid composition were
      measured at multiple skeletal sites. RESULTS: Flaxseed + low-dose estrogen
      therapy resulted in the highest bone mineral density and peak load at the lumbar
      vertebrae, with no effect on bone mineral density or strength in the tibia and
      femur. Flaxseed and flaxseed + low-dose estrogen therapy resulted in
      significantly higher relative levels of alpha-linolenic acid and eicosapentaenoic
      acid and lower levels of linoleic acid, arachidonic acid, and n-6/n-3 ratio in
      the lumbar vertebrae and tibia compared with all other groups. CONCLUSION:
      Flaxseed + low-dose estrogen therapy provides the greatest protection against
      ovariectomy-induced bone loss at the lumbar vertebrae. Moreover, this study is
      the first to demonstrate that flaxseed, rich in alpha-linolenic acid, alters
      fatty acid composition in the ovariectomized rat skeleton.

PMID- 19182695
TI  - Discontinuing postmenopausal hormone therapy: an observational study of tapering
      versus quitting cold turkey: is there a difference in recurrence of menopausal
      symptoms?
AB  - OBJECTIVE: Because no current evidence-based guidelines for postmenopausal
      hormone therapy (HT) discontinuation strategies exist, we compared female
      veterans who tapered HT to those who stopped abruptly with regard to patient
      specific health factors and recurrence of menopausal symptoms. METHODS: We
      identified female veterans who used combined estrogen/medroxyprogesterone HT in
      2001 using the VA Pharmacy Benefits Management database. We then randomly sorted
      and selected 4,000 women for a mailed invitation to participate in a HT survey.
      Women who agreed to participate were mailed the National Women Veterans Hormone
      Replacement Survey. RESULTS: Of 836 participants who discontinued HT, 75% stopped
      cold turkey and 25% tapered. In bivariate analysis, taperers were more likely to
      report higher incomes, less smoking, and more use of alternatives such as vitamin
      E, other dietary supplements, and exercise or yoga for menopausal symptoms. They
      also more frequently reported discussions of menopausal symptoms with providers
      and used HT for menopausal symptoms and had longer median years of HT (P <or=
      0.05 for each comparison). In multivariate analysis, tapering was significantly
      associated with younger age (odds ratio [OR], 0.97; 95% CI, 0.94-0.99),
      initiating HT for menopausal symptoms (OR, 1.66; 95% CI, 1.06-2.62), moderate
      (OR, 1.67; 95% CI, 1.11-2.51) or prolonged (OR, 2.86; 95% CI, 1.76-4.65) years of
      HT use, use of vitamin E (OR, 1.58; 95% CI, 1.02-2.44), use of yoga (OR, 2.41;
      95% CI, 1.05-5.55), and higher income (OR for income <$20.000/y, 0.65; 95% CI,
      0.46-0.92). Separately, tapering HT was significantly associated with lower
      menopausal symptom scores after discontinuation (beta = -0.58 +/- 0.21, P =
      0.01). However, tapering HT also had a significant association with resumption of
      hormones at a later date (OR, 2.06; 95% CI, 1.20-3.52). CONCLUSIONS: Tapering HT
      may lessen recurrence of menopausal symptoms after discontinuation, but some
      women may remain inclined to return to HT. Separately, in the Department of
      Veterans Affairs Healthcare System, female veterans resuming HT need providers
      who can discuss HT options.

PMID- 19182696
TI  - The estrogenic component of tibolone reduces adiposity in female aromatase
      knockout mice.
AB  - OBJECTIVE: To explore the effects of tibolone on adiposity in the absence of
      aromatase and determine which of the hormonal properties of tibolone are exerting
      these effects. METHODS: In this study, vehicle; tibolone; estrogenic (ethinyl
      estradiol [EE]), progestogenic (ORG2058), or androgenic (dihydrotestosterone)
      compounds; or a combination of ORG2058 + EE was administered to 6-month-old
      ovariectomized aromatase knockout (ArKO) mice for a period of 6 weeks. RESULTS:
      In response to tibolone or EE-alone treatments, omental adipose tissue and
      infrarenal adipose tissue weights were significantly reduced (P = 0.004 and P =
      0.01; P = 0.009 and P = 0.014, respectively) compared with those in
      ovariectomized and vehicle-treated ArKO mice. In contrast, adipose tissue weight
      tended to increase after ORG2058-alone treatment. Furthermore, EE in the presence
      of ORG2058 (ORG2058 + EE group) results in little effect on adiposity when
      compared with that in ovariectomized and vehicle-treated ArKO mice, showing that
      ORG2058 can negate the effect of EE. Dihydrotestosterone treatment did not have
      an impact on adipose tissue mass. Adipocyte volume and numbers followed the same
      treatment trends. CONCLUSIONS: In summary, our study in the ArKO mouse has
      confirmed the efficacy of tibolone as a hormone therapy to reduce adipose tissue
      accumulation after menopause and also shows that aromatization of tibolone is not
      required to elicit these estrogenic effects.

PMID- 19182697
TI  - Designing the ideal selective estrogen receptor modulator--an achievable goal?
AB  - Selective estrogen receptor modulators (SERMs), which lack the estrogen steroid
      moiety yet retain the ability to bind the estrogen receptor (ER), are known to
      confer mixed ER agonist or antagonist effects depending on the target tissue. The
      tissue-selective effects of SERMs have led to considerations in the clinical
      profile of an ideal SERM, which would have ER agonist activity in tissues where
      mimicking the action of estrogens is desirable, and ER neutral or antagonist
      activity in tissues estrogens have been shown to adversely stimulate. A number of
      newer SERMs, including bazedoxifene, lasofoxifene, ospemifene, and arzoxifene,
      are currently in clinical development for the prevention and treatment of
      postmenopausal osteoporosis and for other indications. Although the possibility
      of developing a single agent that has all of the desired characteristics of an
      ideal SERM seems to be unlikely, progress in the clinical development of SERMs
      targeted to the ER suggests that these newer compounds may have attributes that
      represent an improvement relative to existing SERMs. Further clinical
      investigation will help to clarify the relative benefits and risks of novel SERMs
      in development within specific indications.

PMID- 19182698
TI  - MF101, a selective estrogen receptor beta modulator for the treatment of
      menopausal hot flushes: a phase II clinical trial.
AB  - OBJECTIVE: To determine the optimal dose, safety, and efficacy of an estrogen
      receptor beta selective Chinese herbal extract, menopausal formula 101 (MF101),
      for treating hot flushes. METHODS: A randomized, blinded trial in 217
      postmenopausal women with hot flushes randomized to 5 or 10 g/day of MF101 or
      placebo for 12 weeks. RESULTS: The effects of 5 g/day of MF101 did not differ
      from those of placebo. After 12 weeks, the mean percent decrease in frequency of
      hot flushes in the 10 g/day group was 12.9% greater than that in the placebo
      group (P = 0.15), the median percent decrease was 11.7% greater than that in the
      placebo group (P = 0.05), and the proportion of women with at least a 50%
      reduction in hot flushes was 16.2% greater than that in the placebo group (P =
      0.03). CONCLUSIONS: Treatment with 10 g/day of MF101 reduces the frequency of hot
      flushes. Trials with higher doses are planned.

PMID- 19182699
TI  - Diurnal variation of corneal shape and thickness.
AB  - PURPOSE: To investigate associations between the diurnal variation in a range of
      corneal parameters, including anterior and posterior corneal topography, and
      regional corneal thickness. METHODS: Fifteen subjects had their corneas measured
      using a rotating Scheimpflug camera (Pentacam) every 3 to 7 h over a 24-h period.
      Anterior and posterior corneal axial curvature, pachymetry and anterior chamber
      depth were analyzed. The best fitting corneal sphero-cylinder from the axial
      curvature, and the average corneal thickness for a series of different corneal
      regions were calculated. Measures of intraocular pressure and axial length were
      also taken at each measurement session. RESULTS: Significant diurnal variation
      was found to occur in both the anterior and posterior corneal curvature and in
      the regional corneal thickness. Flattening of the anterior corneal best sphere
      was observed at the early morning measurement upon waking (p < 0.0001). The
      posterior cornea also underwent a significant steepening (p < 0.0001) and change
      in astigmatism 90/180 degrees at this time. A significant swelling of the cornea
      (p < 0.0001) was also evident upon waking. Highly significant associations were
      found between the diurnal variation in corneal thickness and the changes in
      corneal curvature. CONCLUSIONS: Small but significant diurnal variation occurs in
      the regional thickness and the shape of the anterior and posterior cornea. The
      largest changes in the cornea are typically evident upon waking. The regional
      corneal swelling observed at this time was not uniform, being slightly greater in
      peripheral corneal regions. The pattern of corneal swelling evident on waking
      resulted in a steepening of the posterior, and a flattening of the anterior
      corneal surface.

PMID- 19182700
TI  - Spatial scaling of the binocular capture effect.
AB  - PURPOSE: Binocular "capture" occurs when the perceived visual direction of a
      monocular stimulus is displaced in the direction of the cyclopean visual
      direction of nearby binocular targets. This effect increases with the vertical
      separation of broadband monocular stimuli. The present study investigated whether
      the "capture" effect exhibits a systematic relationship with the spatial
      frequency composition of monocular lines and vertical separation. METHODS:
      Subjects judged the horizontal misalignment of 66 arc min vertical spatial
      frequency ribbons that were temporally interleaved with a random dot depth edge
      (3.2 degrees) for 108 ms. Spatial frequency ribbons were constructed from
      horizontal cosine gratings windowed by a 4 arc min vertical Gaussian envelope.
      The bottom half of the depth edge was presented with zero relative disparity,
      whereas the top half was presented with 10 arc min of crossed or uncrossed
      relative disparity. Four vertical separations (8, 16, 30, and 60 arc min) and
      three ribbon spatial frequencies (1, 4, and 8 cpd) were tested. The horizontal
      ribbon offset corresponding to 50% performance was calculated for each
      combination of depth condition, ribbon spatial frequency, and vertical
      separation. RESULTS: The magnitude of the "capture" effect was consistently
      larger for higher spatial frequency ribbons and decreased with decreasing
      vertical separation. When vertical separation was expressed as multiples of
      spatial periods of the respective ribbon spatial frequency, the magnitude of
      effect was significantly larger for separations greater than about one spatial
      period. CONCLUSIONS: The systematic scaling of the "capture" effect with spatial
      frequency and vertical separation is strongly suggestive of the operation of
      multiple spatial scale mechanisms; similar to those advocated for the processing
      of relative positional acuity with increasing vertical separation of monocular
      targets.

PMID- 19182701
TI  - Validation of optical coherence tomography-based crystalline lens thickness
      measurements in children.
AB  - PURPOSE: To evaluate the validity and repeatability of crystalline lens thickness
      measurements obtained by anterior segment optical coherence tomography (OCT).
      METHODS: Forty-seven normal children (mean age, 11.06 +/- 2.30 yr) had their
      crystalline lens thickness measured with the Visante anterior segment OCT (Carl
      Zeiss Meditec, Dublin, CA) and with conventional corneal touch A-scan
      ultransonography (ultrasound) (Humphrey 820). The subjects' right corneas were
      anesthetized, and their right eyes were cyclopleged. Five ultrasound measurements
      were recorded per eye, and three Visante OCT measurements were recorded per eye.
      Thirty-eight subjects had measurements at a second visit where three additional
      Visante OCT measurements were recorded. RESULTS: The mean of the differences
      between the Visante OCT and ultrasound was -0.045 mm (p = 0.017) with 95% limits
      of agreement from -0.29 to 0.20 mm, indicating that the measurement of
      crystalline lens thickness was slightly thinner with the Visante OCT. When
      validity was assessed using only Visante OCT images that contained the corneal
      reflex, the mean of the differences was 0.019 mm (p = 0.11) with 95% limits of
      agreement from -0.091 to 0.13 mm. For the repeatability of the Visante OCT, the
      mean of the differences between visit one and visit two was -0.008 mm (p = 0.25)
      with 95% limits of agreement from -0.088 to 0.072 mm. Repeatability improved when
      reassessed using only images that contain the corneal reflex; the mean of the
      differences was -0.0001 mm (p = 0.97) with 95% limits of agreement from -0.030 to
      0.030 mm. CONCLUSION: The Visante OCT is a non-contact instrument that is simple
      to use, and it provides valid crystalline lens thickness measurements with
      excellent repeatability. Validity and repeatability are optimized when the
      Visante OCT images contain the corneal reflex and a consistent corneal index
      refraction is applied to the entire image.

PMID- 19182702
TI  - Bifocals in Down Syndrome Study (BiDS): design and baseline visual function.
AB  - PURPOSE: Among children and young people with Down syndrome (DS) there is a high
      prevalence of reduced accommodation. Prescribing bifocals for these patients has
      not become fully clinically accepted, although it would be anticipated to improve
      visual acuity (VA). The aim of this study is to investigate the impact of bifocal
      correction on VA, visual perceptual skills and early literacy development in
      children with DS who have reduced accommodation and who are provided with a
      bifocal correction. This paper describes the study design and the baseline
      optometric findings. METHODS: We have chosen a longitudinal design with frequent
      measures of subtests of performance to control for progression with time. The
      main outcome measures are early literacy and visual perception skills. Secondary
      outcomes are VA and accommodative function. These are measured at baseline, the
      participant followed for 6 months when bifocals are prescribed if necessary, and
      the participants were followed for another 6 months with bifocals. RESULTS:
      Fourteen participants with DS aged 8 to 19 years were enrolled. At baseline 79%
      required a change in their distance spectacle prescription. One hundred percent
      had reduced accommodation both before and after new single vision glasses were
      prescribed. None had an adverse reaction to 0.5 or 1% Cyclopentolate. All the
      subjects were able to perform either a distance or near crowded Patti-pics
      symbols test and 93% were able to perform both. There was a significant
      improvement of near VA with the new single vision spectacles (p = 0.015). The
      mean binocular distance VA was 0.362 +/- 0.17 logMAR whereas binocular near VA
      was 0.489 +/- 0.235. CONCLUSION: This study confirms previous findings of a high
      prevalence of reduced accommodation and shows that near VA is reduced compared to
      distance VA. The present results indicate that all subjects might benefit from
      bifocals.

PMID- 19182703
TI  - Is the disability of arm, shoulder, and hand questionnaire (DASH) also valid and
      responsive in patients with neck complaints.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To evaluate whether the DASH
      is not only a valid and responsive instrument to measure patients with shoulder,
      arm, and hand complaints, but also to evaluate patients with neck complaints.
      SUMMARY OF BACKGROUND DATA: The DASH has shown to be a valid and responsive
      questionnaire to evaluate disability in patients with shoulder, arm, and hand
      complaints. However, patients with shoulder, arm, or hand complaints frequently
      report neck complaints as well. Therefore, a valid and responsive questionnaire
      designed for the whole upper extremity, including the neck, would be very useful
      and practical in upper-extremity research. METHODS: Six hundred seventy-nine
      patients visiting their general practitioner with a new episode of nontraumatic
      complaints of the neck and upper extremity were evaluated by use of
      questionnaires at baseline and at 6-months follow-up. Six (sub)groups were
      formulated according to the location of complaints, including a subgroup with
      complaints in the shoulder-arm-hand region only and a group with complaints of
      the neck only. Disability (DASH), general health [SF-12 (physical and mental
      component)], severity, and persistence of complaints were assessed. Construct
      validity, floor and ceiling effects, and responsiveness were studied. RESULTS.:
      Correlations between the DASH and the other measures within the 6 (sub)groups at
      baseline (construct validity), for the change scores at 6-months follow-up
      (responsiveness), and the responsiveness ratios were classified as acceptable. No
      floor and ceiling effects were found. CONCLUSION: The DASH performed well with
      regard to the a priori hypotheses. This study has shown acceptable validity and
      responsiveness of the DASH for use in patients with nontraumatic neck complaints
      in addition to shoulder, arm, and hand complaints. We would caution against using
      the DASH in patients with neck complaints only, since fewer of the hypotheses
      could be confirmed in this subgroup.

PMID- 19182704
TI  - Pedicle screw surface coatings improve fixation in nonfusion spinal constructs.
AB  - STUDY DESIGN: Biomechanical and histologic analysis. OBJECTIVE: To compare the
      strength of the bone-screw interface of standard uncoated pedicle screws with
      screws treated with hydroxyapatite (HA), titanium plasma spray (TPS), and a
      composite HA-TPS coating. SUMMARY OF BACKGROUND DATA: Transpedicular screw
      fixation has become the gold standard in the treatment of various thoracolumbar
      spinal conditions. Pedicle screw loosening, however, has been reported,
      especially in mechanically demanding constructs or in vertebrae with low bone
      mineral density. METHODS: Six mature porcine were instrumented with 4 types of
      titanium monoaxial pedicle screws (uncoated, HA-only coated, TPS-only coated, and
      HA-TPS composite coated) in a systematically varied, single-blinded fashion.
      After a 3-month survival period, the spines were harvested en-bloc and "time
      zero" control screws were instrumented in adjacent vertebrae. Screw placement and
      bone mineral density were evaluated with a postharvest computed tomography, and
      the strength of the tissue-implant interface was evaluated with a torsional screw
      extraction analysis (60 screws) and a nondecalcified histologic analysis (16
      screws). RESULTS: At 3 months postoperative, peak torque increased for all 3
      types of coated screws (increased fixation) and decreased significantly for the
      uncoated screws (P < 0.001). Although 3-month peak torque was not statistically
      different between the 3 screw coatings, 4 of 10 TPS-only coated screws had a peak
      torque that was nearly 0 (<0.1 N m) versus only 1 of 10 HA-only screws and 0 of
      10 HA-TPS composite screws. Histologic analysis confirmed the biomechanical
      findings with improved osseointegration in the HA-only and HA-TPS composite
      screws. CONCLUSION: Pedicle screw coatings that promote mechanical interlocking,
      TPS, or direct osteoblast bonding(HA) increased screw fixation in this nonfusion
      model. More non-HA coated screws, however, were thought to be "loose" with a
      nearly zero peak extraction torque and fibrous encapsulation. Increased
      osseointegration with HA may result in a decreased incidence of screw loosening
      and improved outcomes of transpedicular spinal instrumentation in nonfusion
      procedures.

PMID- 19182705
TI  - Grafting of human bone marrow stromal cells into spinal cord injury: a comparison
      of delivery methods.
AB  - STUDY DESIGN: Three groups of 6 rats received subtotal cervical spinal cord
      hemisections followed with marrow stromal cell (MSC) transplants by lumbar
      puncture (LP), intravenous delivery (IV), or direct injection into the injury
      (control). Animals survived for 4 or 21 days. OBJECTIVE: Cell therapy is a
      promising strategy for the treatment of spinal cord injury (SCI). The mode of
      cell delivery is crucial for the translation to the clinic. Injections directly
      into the parenchyma may further damage already compromised tissue; therefore,
      less invasive methods like LP or IV delivery are preferable. SUMMARY OF
      BACKGROUND DATA: Human MSC are multipotent mesenchymal adult stem cells that have
      a potential for autologous transplantation, obviating the need for immune
      suppression. Although previous studies have established that MSC can be delivered
      to the injured spinal cord by both LP and IV, the efficacy of cell delivery has
      not been directly compared with respect to efficacy of delivery and effects on
      the host. METHODS: Purified MSC from a human donor were transplanted into the CSF
      at the lumbar region (LP), into the femoral vein (IV), or directly into the
      injury (control). After sacrifice, spinal cord sections were analyzed for MSC
      graft size, tissue sparing, host immune response, and glial scar formation, using
      specific antibodies and Nissl-myelin staining. RESULTS: LP delivery of MSC to the
      injured spinal cord is superior to IV delivery. Cell engraftment and tissue
      sparing were significantly better after LP delivery, and host immune response
      after LP delivery was reduced compared with IV delivery. CONCLUSION: LP is an
      ideal minimally invasive technique to deliver cellular transplants to the injured
      spinal cord. It is superior to IV delivery and, together with the potential for
      autologous transplantation, lends itself for clinical application.

PMID- 19182706
TI  - Stem cell factor prevents neuronal cell apoptosis after acute spinal cord injury.
AB  - STUDY DESIGN: A rat spinal cord injury (SCI) model and immunohistochemistry were
      used to examine the levels of expression of stem cell factor and c-kit. In
      addition, we examined whether intraperitoneal administration of stem cell factor
      could prevent neural cells apoptosis after acute SCI. OBJECTIVE: To evaluate the
      antiapoptotic effect of stem cell factor after SCI. SUMMARY OF BACKGROUND DATA:
      It is well known that the mode of delayed neuronal and glial cell death after SCI
      is apoptosis. Inhibition of apoptosis might thus promote neurologic improvement
      after SCI. Stem cell factor and its receptor c-kit exhibit pleiotropic effects in
      early hematopoiesis, and are also known to prevent hematopoietic progenitor cell
      apoptosis. Stem cell factor has recently been reported to be a survival factor
      for neural stem cells in vitro. We examined the levels of expression of stem cell
      factor and c-kit in normal and injured rat spinal cord. In addition, we examined
      whether stem cell factor prevents neural cell apoptosis after acute SCI. METHODS:
      We examined the expression of stem cell factor and c-kit in spinal cord after
      injury by quantitative RT-PCR and immunohistochemistry. Antiapoptotic effects of
      stem cell factor were examined using rats with SCI that received stem cell factor
      intraperitoneally, and were examined immunohistochemically with anticleaved PARP
      antibody and antiactive caspase-3 antibody between 1 and 3 days after injury.
      RESULTS: Upregulation of stem cell factor and c-kit expression occured after SCI.
      We also found that neurons express stem cell factor, and neurons and
      oligodendrocytes express c-kit after SCI. In addition, intraperitoneal
      administration of stem cell factor prevented spinal neural cells apoptosis after
      injury. CONCLUSION: These findings suggest the possibility that stem cell factor,
      a hematopoietic cytokine, could be useful as an agent for treatment of SCI.

PMID- 19182708
TI  - [MRI for breast cancer staging: does it improve patient management?].

PMID- 19182707
TI  - [The SFR is a hundred years old].

PMID- 19182709
TI  - [Functional MR urography in children].
AB  - MR Urography (MRU) provides both morphologic and functional information without
      radiation exposure. It enables the assessment of split renal function, excretion,
      and quantification of obstruction. MRU is thus complementary to ultrasonography
      in the assessment of pre- and post-natal obstructive uropathies in children. If
      available, MRU should be definitely preferred to intravenous urography.

PMID- 19182710
TI  - [Sinonasal cavities: CT imaging features of anatomical variants and surgical
      risk].
AB  - Anatomical variants of the sinonasal cavities are common. About 15 major variants
      are described (nasal septal deviation is present in up to 62% of the population).
      Because the may lead to complications at the time of endovascular procedures or
      endoscopic sinonasal surgery (vascular, nervous, or osseous injury), there
      detection has medicolegal implications. Knowledge of anatomical variants by
      radiologists and ENT surgeons is thus required. We will describe these variants,
      their imaging features, frequency, implications and associated risk of potential
      complication.

PMID- 19182711
TI  - [Clip migration after stereotactic macrobiopsy and presurgical localization:
      technical considerations and tricks].
AB  - PURPOSE: Clip migration occurs frequently in clinical practice (13-20%),
      irrespective of the approach. The purpose of this article is to suggest tricks in
      order to decrease clip migration and optimize presurgical localization. MATERIALS
      AND METHODS: Retrospective study of breast macrobiopsy from a lateral approach
      performed between March 2003 and June 2004: 447 clips were placed. Sixty clips
      showed migration>20 mm, due to the accordion effect in 59 cases (98.4%). These 59
      procedures were analyzed to try and understand the underlying mechanisms of clip
      migration. RESULTS: From these 59 clips, more migrations were noted on CC
      compression (16.6%) compared to MLO compression (5.2%). This difference was
      statistically significant. Therefore, we promote the use of MLO compression. This
      incidence also allows optimal presurgical localization in case of clip migration,
      by placing the patient in the same position while modulating depth based on the
      extent of clip displacement. CONCLUSION: For quality purposes, it is imperative
      to know the clip position relative to the initial target. By using MLO
      compression from a lateral approach, it is possible to reduce clip migration and
      optimize future presurgical localization.

PMID- 19182712
TI  - [Virtual interventional radiology: evaluation of performances as a function of
      experience].
AB  - PURPOSE: To determine the value of an angioplasty simulation to differentiate the
      users based on their level of experience. To determine the perceived usefulness
      of an angioplasty simulation program. MATERIALS AND METHODS: Forty-six
      radiologists performed a renal angioplasty on a VIST simulator (Mentice
      Corporation, Gothenburg, Sweden); the procedure was completed by 41 radiologists.
      The radiologists were divided into two groups based on the level of experience.
      Quantitative variables analyzed included procedure duration time and fluoroscopy
      time. The radiologists then completed a questionnaire evaluating the simulation
      program. RESULTS: Radiologists with more than 2 years of clinical experience
      (n=14) performed the procedures faster (20.4 min vs 27.4 min, p<0.01) using less
      fluoroscopy time (7.8 min vs 11.2 min, p<0.05) than others. Radiologists
      performing more than 2 procedures per month (n=14) performed the procedures
      faster (19.4 min vs 27.9 min, p<0.01) using less fluoroscopy time (7.4 min vs
      11.3 min, p<0.05) than other (n=27). The participating radiologists indicated
      that the simulation was realistic. CONCLUSION: Procedure duration time and
      duration of fluoroscopy were criteria able to differentiate the users based on
      their level of experience. The educational value of the simulation program was
      perceived as helpful by the users.

PMID- 19182713
TI  - [Combined apical emphysema and basal fibrosis syndrome (emphysema/fibrosis
      syndrome): CT imaging features and pulmonary function tests].
AB  - PURPOSE: To describe the high resolution CT (HRCT) imaging and functional
      features of the emphysema/fibrosis syndrome. PATIENTS AND METHODS: A total of 61
      patients were included based on HRCT. We have quantified the extent of fibrosis
      and emphysema lesions and a combined score was calculated. The scores were
      correlated to pulmonary function test parameters and specific HRCT features were
      described. RESULTS: The emphysema and fibrosis scores correlated with functional
      parameters of obstruction and restriction respectively. The combined score
      correlated with the reduction in DLCO and degree of pulmonary hypertension. Three
      HRCT patterns were identified: progressive transition (n=23, 38%) with diffuse
      emphysema (centrilobular and/or bullous) and zone of transition between bullae
      and honeycombing; paraseptal emphysema (n=13, 21%) with predominant subpleural
      bullae of enlarging size at the bases; separate processes (n=14, 23%) with
      independent areas of fibrosis and emphysema. Eleven patients (18%) could not be
      classified. The HRCT imaging features changed based on TLC (p=0.04) and FEV1/FVC
      (p=0.01). CONCLUSION: The emphysema/fibrosis syndrome may be associated with
      different patterns on HRCT corresponding to specific profiles on pulmonary
      function tests.

PMID- 19182714
TI  - [Lung signal on fetal MRI: normal values and usefulness for congenital
      diaphragmatic hernia].
AB  - PURPOSE: To demonstrate the feasibility of lung signal measurements on fetal MRI,
      present normal signal intensity curves, and assess its value to predict pulmonary
      hypoplasia. PATIENTS AND METHODS: Prospective multicentric study of 115 fetuses
      without lung disease and 33 fetuses with left diaphragmatic hernia and high risk
      of pulmonary hypoplasia. Signal measurements were obtained of the lungs, liver
      and psoas from fast heavily T2W sequences (HASTE, 2 measurements and 2 orthogonal
      planes for each organ, oval-shaped ROI of 1 cm2 for lungs and liver, and 0.5 cm2
      for the psoas). RESULTS: No direct linear relationship existed between lung
      signal intensity and gestational age. A direct linear relationship existed
      between liver signal and gestational age, and between psoas signal and
      gestational age. An exponential relationship existed for the ratios left
      lung/liver, right lung/liver, left lung/psoas and right lung/psoas. The inter
      observer agreement was excellent, ranging between 0.888 and 0.926. Significant
      differences were observed between normal fetuses and fetuses with diaphragmatic
      hernia for the right lung/liver and left lung/psoas ratios. CONCLUSION: Normal
      fetal lung signal intensity curves can be obtained. Lungs at risk of hypoplasia
      presented significant alterations of signal ratios. The prognostic value of such
      results requires additional postnatal clinical follow-up.

PMID- 19182715
TI  - [Ciliated hepatic cyst: report of one case and review of the literature].

PMID- 19182716
TI  - [Suboccipital Pott's disease: a case report].

PMID- 19182717
TI  - [Concomitant pulmonary Langerhans cell histiocytosis and malignant lymphoma:
      report of two cases].

PMID- 19182719
TI  - [Answer to December e-quid].

PMID- 19182718
TI  - [Dilatation of cervical epidural veins secondary to iatrogenic intracranial
      hypotension].

PMID- 19182721
TI  - [Percutaneous brachial access: a few simple considerations].
AB  - This letter is with regards to the recently published article by Vidal et al. in
      the Journal Francais de Radiologie Medicale. A clarification of US and
      venographic techniques of brachial venous catheterization and related
      complications are presented. The main indications for PICC line and subcutaneous
      port placement are described.

PMID- 19182722
TI  - Matrix metalloproteinase-2 involvement in breast cancer progression: a mini
      review.
AB  - Matrix Metalloproteinase-2 (MMP-2) is an enzyme that degrades components of the
      extracellular matrix and thus plays a pivotal role in cell migration during
      physiological and pathological processes (e.g. gastric, pancrcreatic, prostate,
      and breast cancer). MMP-2 expression is dependent on extracellular matrix
      metalloproteinase inducer (EMMPRIN), Her2/neu, growth factors, cytokines, and
      hormones. Pro-MMP-2 activation needs MT1-MMP and TIMP-2 contribution. The active
      forms of MMPs subsequently release a cascade of activation of the remaining pro
      MMPs. Inactivation of the physiological function of MMPs, or even pro-MMPs, is
      accomplished by non-covalent TIMP binding. The detection of active MMP-2 alone or
      the rate of pro-MMP-2 and active MMP-2 is considered a very sensitive indicator
      of cancer metastasis. Modulation of MMP-2 expression and activation through
      specific inhibitors and activators may thus provide a new mechanism for breast
      cancer treatment. Degradation of the cellular network established by adhesion
      molecules such as E-cadherin or ALCAM/CD166 causes tumor tissue relaxation,
      increases metastasis, and correlates with shortened survival in patients with
      primary breast carcinoma. A low level of MMP-2 is linked to favorable prognosis
      in patients with a hormone receptor-negative tumor, usually associated with high
      risk. Blocking MMP-2 secretion and activation during breast carcinoma development
      may decrease metastasis. Besides zoledronic acid and bisphosphonates, the new
      synthetic metalloproteinase blockers (MMPIs) batimastat, marimastat, and
      tetracycline derivates have been investigated in anticancer therapy. Recent
      research shows that modified synthetic siRNA targeting TIMP-2 may also regulate
      the balance between MMPs and TIMP-2 and thus decrease the degradation of
      extracellular matrix and prevent distant metastasis.

PMID- 19182723
TI  - Facts and figures on the QJNM&MI: a report by the outgoing editor.

PMID- 19182724
TI  - Radiobelled white blood cells or FDG for imaging on inflammation and infection?

PMID- 19182725
TI  - PET and SPECT imaging of apoptosis in vulnerable atherosclerotic plaques with
      radiolabeled Annexin A5.
AB  - Atherosclerosis still represents killer number one in industrialized nations, and
      is starting to have increased impact in developing countries. Atherosclerotic
      plaques are the net result of a complex interplay between vascular cholesterol
      deposition, inflammatory activity and extracellular matrix formation. The result
      is luminal narrowing of arteries, which may ultimately lead to compromised blood
      flow to essential body organs, most notoriously to the heart. Most of the
      cardiovascular events that are caused by atherosclerosis, such as acute
      myocardial infarction or stroke, are the result of a transition of so-called
      stable atherosclerotic plaques to vulnerable plaques, that are prone to rupture.
      The direct consequence of atherosclerotic plaque rupture is exposure of
      thrombogenic plaque constituents to the blood, leading to instant local thrombus
      formation. The formation of this localized thrombus may ultimately result in
      sudden obstruction of blood flow and consequent infarction of distal tissue.
      Clinical risk profiling methods, such as the Framingham and Procam risk scores,
      are reasonable predictors of myocardial infarction over a 10-year time-span.
      However, the challenge remains to identify those patients with a very high risk
      of suffering from myocardial infarction in the coming months. Imaging may provide
      the necessary diagnostic information to identify such individuals. The transition
      of stable atherosclerotic plaques to vulnerable plaques is typically heralded by
      inflammation, thinning of the overlying fibrous cap, and the presence of a large
      necrotic core. Apoptosis is linked to all of these features of plaque
      vulnerability, and may, therefore, provide uniquely useful targets for the
      identification of plaque vulnerability. In recent years, a number of molecular
      imaging technologies have been developed to image apoptosis, which will be
      discussed in this review. Further development of apoptosis imaging technologies
      may aid us in the years to come in the quest to identify patients with critical
      cardiovascular risks, to treat myocardial infarction in its imminent, instead of
      its evident phase.

PMID- 19182726
TI  - FDG-PET for the detection of infected vascular grafts.
AB  - Graft infection following prosthetic vascular reconstruction is an uncommon but
      severe complication. The clinical presentation is often subtle and non-specific
      and may occur long after surgery. While defining a prosthetic vascular graft
      infection can be difficult, early diagnosis and treatment are essential for the
      correct choice of treatment in order to prevent further complications as well as
      the high morbidity and mortality associated with repeat surgery and removal of
      infected grafts. False positive results may lead to unnecessary surgery while
      failure to diagnose graft infection may have life-threatening sequels. Scarce
      literature that is currently available regarding the role of fluorodeoxyglucose
      (FDG) imaging for assessment of vascular graft infection suggests that this
      modality may represent reliable non-invasive imaging modality in this specific
      clinical setting. Hybrid positron emission tomography (PET)/computed tomography
      (CT), combining CT with PET, increases the test specificity and thus improves
      diagnostic accuracy. The precise anatomic localization of increased FDG uptake
      provided by PET/CT enables accurate differentiation between graft and adjacent
      soft tissue infection leading to more accurate diagnosis and subsequent optimized
      therapeutic strategy.

PMID- 19182727
TI  - FDG-PET in patients with painful hip and knee arthroplasty: technical
      breakthrough or just more of the same.
AB  - The two major complications of joint replacement are loosening and infection. A
      reliable differentiation between these pathological processes can be challenging
      because both are accompanied by similar clinical symptoms. Nuclear medicine
      examinations are frequently used in the management of patients with painful
      arthroplasty since they are not impaired by the metallic implants. This report
      evaluates the pooled data of the major publications in the English literature
      analyzing the accuracy of the triple-phase bone scan (TPBS), white blood cell
      imaging (WBC imaging) and positron emission tomography (PET). TPBS yielded the
      least favorable results with an accuracy of 80% for hip prostheses and 81% for
      knee arthroplasty. PET finished second with values of 89% (hip) and 83% (knee),
      respectively. WBC imaging exceeded the results of TPBS and PET, yielding values
      of 91% (hip) and 84% (knee). Although bested by WBC imaging, PET is still highly
      attractive since it combines several of the positive aspects of the two other
      methods. Its accuracy is only slightly lower than that of WBC imaging while at
      the same time it provides most of the comfort of the bone scan: only one
      injection, no processing of blood samples and the results are available within 4
      h. In conclusion, the data indicate that PET is a highly effective imaging
      procedure for diagnosing complications of hip and knee arthroplasty. Its only
      limitations are the restricted availability and the costs. Whether the same holds
      true for PET/CT has yet to be proven. While the hybrid devices are highly
      beneficial in oncology, their use in the diagnosis of pathological processes of
      joint prostheses is questionable due to the CT artifacts induced by the metallic
      implants. WBC imaging on the other hand has to be considered as gold standard
      since it yields the highest accuracy of the three diagnostic approaches,
      especially when combined with bone marrow scintigraphy. In departments where
      neither the equipment nor the know-how for PET and WBC imaging is available, TPBS
      is a viable alternative. Compared to the other diagnostic approaches it yields a
      slightly lower accuracy, but excels in simplicity and cost-effectiveness.
      Especially in knee prostheses, it nearly reaches the accuracy of WBC imaging and
      PET (TPBS 81%, WBC imaging 84%, PET 83%).

PMID- 19182728
TI  - FDG-PET in patients with fever of unknown origin: the importance of diagnosing
      large vessel vasculitis.
AB  - This review analyzes the impact of 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)
      positron emission tomography (PET) in the diagnostic work-up of classic fever of
      unknown origin (FUO) according to the criteria first proposed by Petersorf in
      1961 and later modified by Durack et al. in 1991. Algorithms currently used in
      this diagnostic process are not strictly evidence based up to now. FDG
      accumulates in malignant tissues, but also in inflammatory cells by the
      overexpression of facultative glucose transporter-isotypes (mainly GLUT-1 and
      GLUT-3) and by an overproduction of glycolytic enzymes. Therefore, this technique
      covers a broad spectrum of possible etiologies for FUO. Once imaged, these
      lesions can be further investigated by other (e.g. invasive) and more specific
      methods. Until now, four prospective studies using FDG-PET in patients with
      classic FUO, encompassing 167 patients in total are published. Three
      retrospective studies with 125 patients are also available. These studies are
      discussed and weighted according to the control of selection-bias that was
      performed. An interstudy-bias may also be present resulting from a considerable
      variability in causes of FUO. A low number of diagnostic scans in a study may
      sometimes be related to a high rate of fevers caused by miscellaneous disorders
      or to a high rate of undiagnosed patients. In these disease categories, focal
      pathologies that can be imaged with FDG-PET, are rare. A high number of
      diagnostic scans is always related to a high prevalence of patients with medium-
      and large-vessel vasculitis. Available data indicate that FDG-PET has the
      potential to play an important role as a second line procedure in the management
      of about 1/3 of patients with classic FUO. It is expected that hybrid imaging
      (PET/computed tomography [CT]; PET/magnetic resonance imaging [MRI]) will improve
      the diagnostic impact of FDG-PET further, but prospective data about the value of
      this methods are currently not available. The question as to how these new
      techniques can be implemented into an evidence based diagnostic algorithm, can
      only be resolved within a multidisciplinary setting, avoiding both selection- and
      interstudy-bias whenever possible.

PMID- 19182729
TI  - FDG-PET in inflammatory bowel disease.
AB  - Accurate, inexpensive, non-invasive studies in evaluation of inflammatory bowel
      disease (IBD) would represent a significant advancement in identifying and
      measuring disease activity. There is new evidence that positron emission
      tomography (PET) scanning can fulfill many of these criteria. The aim of this
      review is to report the studies pertaining to the use of PET in IBD and provide
      an evidence-based approach on how to use PET clinically in IBD. Searching Medline
      and the Cochrane Database of Clinical Trails on July 18, 2008 identified 12
      relevant manuscripts for review. Types of studies of PET in IBD include the
      incidental identification of IBD during studies performed for other indications,
      the evaluation of suspected IBD and the assessment of known IBD. PET has been
      studied in both children and adults and has shown excellent sensitivity for
      detecting active bowel inflammation, but with poor specificity in some studies.
      PET alone appears sufficient for the evaluation of ulcerative colitis, but
      PET/computed tomography provides considerably more information over PET alone in
      the evaluation of Crohn's disease. Current clinical applications for PET in IBD
      include its use in the early evaluation of IBD, especially in children who may
      not tolerate an invasive test such as colonoscopy; and its use in differentiating
      between a flare of IBD versus the onset of a non-inflammatory process causing
      similar symptoms in patients with known IBD. Many unanswered questions remain,
      but PET appears to be a promising tool in the non-invasive evaluation of IBD.

PMID- 19182730
TI  - Scintigraphic imaging in renal infections.
AB  - The scintigraphic imaging modality of choice in the evaluation of renal
      infections is renal cortical scintigraphy utilizing [(99m)Tc]dimercaptosuccinic
      acid (DMSA). This technique is able to demonstrate upper tract involvement with
      infection and to assess for the presence of renal cortical scarring following a
      urinary tract infection (UTI). There are recent publications advocating its use
      to determine which patients need to proceed to further investigation with
      cystography. It is also being utilized in the evaluation of different treatment
      regimes used in patients with UTI. Fluorodeoxyglucose (FDG)-PET and leukocyte
      scanning have only a minor role in the diagnosis of renal infection. Their main
      application is in the diagnosis of renal cyst infections in patients with
      polycystic renal disease.

PMID- 19182731
TI  - Labeling monocytes for imaging chronic inflammation.
AB  - With growing interest in cell-based scintigraphic diagnosis or therapy
      monitoring, there is an increasing demand for non-invasive observation and
      quantification of cell trafficking in the preclinical and clinical setting.
      Monocytes are members of the human mononuclear phagocyte system originating from
      a myeloid precursor in the bone. Labeled monocytes are being used for
      investigation of pathogenesis like atherosclerosis and for monitoring of
      therapeutic intervention in inflammatory diseases like rheumatoid arthritis.
      Labeling mononuclear cells at high specific activity without affecting their
      biological functions allows (delayed) non-invasive imaging with g or PET cameras.
      Monocytes labeled before their final differentiation into macrophages or
      dendritic cells may reveal centers of inflammation in a patient and, thereby,
      contribute to scintigraphic diagnosis. Macrophages or dendritic cells may be in
      vitro cultured and by means of genetic transformation specified towards specific
      targets prior to re-injection, an approach with therapeutic potency. This review
      addresses issues on autologous monocytes, particularly their properties and
      labeling for non-invasive in vivo radionuclide imaging of chronic inflammation.

PMID- 19182732
TI  - Imaging with FDG labeled leukocytes: is it clinically useful?
AB  - In vivo and in vitro labeled leukocytes have been shown to be very effective in
      detecting different infectious and inflammatory conditions. The model of labeled
      leukocyte imaging is based on the powerful mechanisms of chemotaxis exerted on
      activated leukocytes by chemo-attractants. The avidity of inflammatory cells for
      fluorodeoxyglucose (FDG) has led to the concept of labeling leukocytes with
      [(18F)]FDG ex vivo. This concept combines cell-bound radionuclide trafficking
      from the blood pool compartment to the lesion with the high resolution of
      positron emission tomography (PET) imaging. The further benefits of having a
      correlated anatomical map by implementing the acquisition on a hybrid
      PET/computed tomography (CT) device are obvious. The feasibility and the
      potential value of leukocyte PET(/CT) imaging in infection have been
      demonstrated. The available data suggest a high accuracy of the method. Still,
      leukocyte PET/CT should not be considered as the endpoint of infection imaging,
      since it only meets a part of the criteria of the ideal infection imaging agent.
      However, the common clinical need for specific detection of infection with
      anatomical precision, the availability of the components necessary for performing
      leukocyte PET/CT, their lack of toxicity or adverse effects and the absence of
      more superior tracers on the commercial market make it worthwhile to further
      investigate leukocyte PET/CT imaging in larger prospective series. The advantages
      of leukocyte PET/CT over the more conventional nuclear medicine and radiological
      methods makes this imaging tool likely to be useful in certain subsets of
      infected patients.

PMID- 19182733
TI  - Hybrid imaging systems in the diagnosis of osteomyelitis and prosthetic joint
      infection.
AB  - Early diagnosis of osteomyelitis and prosthetic bone infection is essential for
      successful therapy and prevention of complications. Nuclear medicine offers a
      variety of modalities for this aim, including both single photon emission
      tomography (SPET) and positron emission tomography (PET) radiopharmaceuticals.
      The main limitation of these functional images is the fact that they are lacking
      the structural delineation of the pathologic processes; this important drawback
      can sometimes render interpretation difficult and diminish the diagnostic
      capability. The recent availability of hybrid SPET/computed tomography (CT) and
      PET/CT devices that acquire both functional and anatomical data can solve these
      problems. In fact, the combination of SPET or PET with CT provides exact
      anatomical registration with bone and joint lesions and improves the accuracy of
      the nuclear medicine images. This article reviews the currently available
      literature and addresses the use of hybrid systems in the diagnosis of
      osteomyelitis and prosthetic bone infection. The first reports indicate that
      hybrid imaging is very useful in these indications, because it is able to provide
      further information of clinical value in several cases. The advantage of
      accurately localizing the areas of increased radiotracer uptake allows a precise
      differentiation between soft tissue and bone infection, that is crucial for the
      choice of therapy and patients' management. However, data are still very limited
      and further studies are needed to verify if hybrid imaging may really become
      clinically relevant in the near future for early diagnosis of osteomyelitis and
      prosthetic bone infection.

PMID- 19182734
TI  - Labeled leukocyte imaging: current status and future directions.
AB  - The ability to radiolabel inflammatory cells that migrate to foci of infection
      was a significant milestone in the evolution of infection imaging. More than 20
      years after being approved for clinical use in the United States, labeled
      leukocyte imaging using cells labeled with [(99m)Tc]exametazime or [(111)In]oxine
      remains the radionuclide procedure of choice for diagnosing most infections in
      the immunocompetent population. In the central nervous system, labeled leukocyte
      imaging is useful for differentiating infection from tumor; in the postoperative
      setting, this test facilitates the differentiation of infection from normal
      postoperative changes. Labeled leukocyte imaging accurately diagnoses mycotic
      aneurysms and infected prosthetic vascular grafts. In patients with fever of
      unknown origin, a negative study excludes, with a high degree of certainty,
      infection as the source of fever. Labeled leukocyte imaging accurately diagnoses
      pedal osteomyelitis and is useful for distinguishing infection from the
      neuropathic joint in this population. Together with bone marrow imaging, the
      labeled leukocyte study is the imaging procedure of choice for diagnosing
      prosthetic joint infection. There are limitations to the test. Most of the
      leukocytes labeled are neutrophils, and the procedure is most useful for
      detecting neutrophil-mediated inflammatory processes, i.e., bacterial infections.
      It is less useful for illnesses in which the predominant cellular response is
      other than neutrophilic, such as most opportunistic infections and spinal
      osteomyelitis. The in vitro labeling procedure is time consuming and is not
      routinely available. Results of in vivo leukocyte labeling methods have been
      variable; none are available in the United States. Labeled leukocyte imaging
      suffers from inherently poor quality images. Single photon emission compute
      tomography/computed tomography improves lesion localization, and will undoubtedly
      improve the accuracy of the test. Efforts to develop methods of labeling white
      cells with positron emitting compounds are underway and, if successful, should
      further strengthen the role of nuclear medicine in infection imaging.

PMID- 19182735
TI  - Electromagnetic brain activity in higher frequency bands during automatic word
      processing indicates recovery of function in aphasia.
AB  - AIM: Little is known about how treatment affects the neural substrate of language
      function in stroke sufferers. In the present study authors investigated neuronal
      correlates of treatment induced recovery of language functions in patients with
      chronic aphasia. METHODS: In 10 chronic aphasia patients and 10 age- and gender
      matched control participants, evoked high-frequency activity (HFA, >20 Hz) was
      determined from the magnetoencephalogram in an automatic word recognition task,
      in which content, function, and pseudowords were visually presented at fast rate
      (350-ms). Recording was repeated after 2 weeks, in aphasics after intensive
      language training to evaluate training effects, in controls to establish HFA
      stability. RESULTS: In the first recording, bilateral HFA distribution in
      controls contrasted right-hemispheric predominance in the patients. After
      training, this right>left asymmetry in aphasics was reduced to a bilateral
      pattern similar to controls. While word class did not substantially affect HFA
      patterns in the two groups, enhanced right-hemispheric HFA in the patients varied
      with better language function (test performance) prior to training, while after
      training, left-temporal function- and pseudoword evoked HFA varied with
      performance in tests of written language. CONCLUSION: Results suggest that HFA
      might serve as a measure in the evaluation of rehabilitation efforts in chronic
      aphasia: enhanced right-hemispheric HFA might indicate compensatory activation of
      contralateral language areas, which tends towards patterns comparable to normal
      subjects after effective language training.

PMID- 19182736
TI  - Psychological distress in patients with Charcot-Marie-Tooth disease.
AB  - AIM: Charcot-Marie-Tooth disease (CMT) is a genetic neuropathy that causes
      variable degrees of gait and handgrip impairment, and reduces quality of life.
      The large majority of CMT patients are moderately affected and lead almost a
      normal life despite facing numerous difficulties and physical and psychological
      suffering. This study is aimed at investigating the possible presence of
      psychological distress in this population. METHODS: Fifty-three patients (F=30,
      M=23; age: 16-64 years; disease duration: 1-53 years), with variable gait and
      handgrip impairments but still able to ambulate independently, referred to a
      specialized rehabilitation service, and 53 sex and age matched controls were
      administered with the Kellner's Symptom Questionnaire Italian validated version.
      RESULTS: The mean scores of patients, both as a whole and as divided in groups
      according to sex, age and lower limb impairment severity, did not differ
      significantly from those of controls (P>0.05). CONCLUSION: Patients with CMT are
      able to cope with the problems caused by their disease without developing more
      psychological distress than unaffected subjects, probably as the result of a
      comprehensive adaptation, favoured by the long disease duration, relative
      mildness of symptoms, good cognitive functioning and availability of
      rehabilitative resources.

PMID- 19182737
TI  - Wernicke's encephalopathy and pancreatic encephalopathy after necrotic
      hemorrhagic pancreatitis. A case report.
AB  - This case report describes a case of acute necrotic-hemorrhagic pancreatitis
      complicated by Wernicke's encephalopathy (WE) and stresses the importance of a
      correct dietetic regimen. A 39-year-old Chinese male patient with negative remote
      pathological anamnesis was hospitalized in the Medical Department with a
      diagnosis of gallstones. The clinical course was complicated with the onset of
      acute pancreatitis. Enteral fasting was imposed with intravenous feeding without
      vitamin supplementation. The progressive worsening of the clinical,
      radiodiagnostic and laboratory profile combined with deterioration in the state
      of consciousness promoted, on the 36th day exploratory laparotomy revealed
      necrotic-hemorrhagic pancreatitis. The patient was, therefore, admitted to the
      Intensive Care Unit in a deep coma. The recent medical history, neurological
      examination, and encephalic computed tomography suggested a revealing diagnosis
      of WE combined with pancreatic encephalopathy.

PMID- 19182738
TI  - Management of atrial fibrillation in the elderly.
AB  - Atrial fibrillation (AF) is associated with a higher incidence of mortality,
      stroke, and coronary events than is sinus rhythm. AF with a rapid ventricular
      rate may cause a tachycardia-related cardiomyopathy. Immediate direct-current
      (DC) cardioversion should be performed in patients with AF and acute myocardial
      infarction, chest pain due to myocardial ischemia, hypotension, severe heart
      failure, or syncope. Intravenous beta blockers, diltiazem, or verapamil may be
      administered to slow immediately a very rapid ventricular rate in AF. An oral
      beta blocker, verapamil, or diltiazem should be used in persons with AF if a fast
      ventricular rate occurs at rest or during exercise despite digoxin. Amiodarone
      may be used in selected patients with symptomatic life-threatening AF refractory
      to other drugs. Digoxin should not be used to treat patients with paroxysmal AF.
      Nondrug therapies should be performed in patients with symptomatic AF in whom a
      rapid ventricular rate cannot be slowed by drugs. Paroxysmal AF associated with
      the tachycardia-bradycardia syndrome should be treated with a permanent pacemaker
      in combination with drugs. A permanent pacemaker should be implanted in patients
      with AF and symptoms such as dizziness or syncope associated with ventricular
      pauses greater than 3 seconds which are not drug-induced. Elective DC
      cardioversion has a higher success rate and a lower incidence of cardiac adverse
      effects than does medical cardioversion in converting AF to sinus rhythm. Unless
      transesophageal echocardiography has shown no thrombus in the left atrial
      appendage before cardioversion, oral warfarin should be given for 3 weeks before
      elective DC or drug cardioversion of AF and continued for at least 4 weeks after
      maintenance of sinus rhythm. Many cardiologists prefer, especially in older
      patients, ventricular rate control plus warfarin rather than maintaining sinus
      rhythm with antiar-rhythmic drugs. Patients with chronic or paroxysmal AF at high
      risk for stroke should be treated with long-term warfarin to achieve an
      International Normalized Ratio of 2.0 to 3.0. Patients with AF at low risk for
      stroke or with contraindications to warfarin should be treated with aspirin 325
      mg daily.

PMID- 19182739
TI  - Leptin and obesity.
AB  - Leptin, a protein containing 167 amino acids, demonstrates structural
      similarities with cytokine family and is mainly produced by adipocytes. The
      leptin receptor (OB-R) is a large membrane spanning protein that belongs to the
      gp 130 family of cytokine class I receptors. Besides the neuroendocrine effects
      of leptin in the control of food intake and energy expenditure, binding of this
      hormone has been proven in intestine, liver, kidney, skin, stomach, heart,
      spleen, lung, and so on. Thus leptin affects maternal, fetal and placental
      function, it appears to act as an endocrine and paracrine factor for the
      regulation of reproduction and puberty, prevents ectopic lipid deposition,
      modifies insulin sensitivity in the muscle or liver, and links the immune and
      endocrine systems. The LEP gene encodes for leptin. It has been localized in
      humans on the 7 alpha 31.3 chromosome and consists of three exons separated by
      two introns. In humans, a mutation in the LEP gene was reported in two children
      with the same cosanguineous pedigree. Other studies reported a polymorphism in
      the promoter untranslated exon 1 of the LEP gene (A19G), a polymorphism C(-188)A
      in the promoter region of the LEP gene (17) and a mutation at codon V110M. The
      biologic activities of leptin on target tissues are carried out through binding
      to a specific receptor, LEPR. LEPR maps in humans to the 1p31 chromosome.
      Variants commonly occur, which cause two nonconservative changes:lysine to
      asparagine at codon 656 (AAG to AAC) in exon 14 (K656N); lysine to arginine at
      codon 109 (AAG to AGG) in exon 4 (K109R); a nonconservative change glutamine to
      arginine at codon 223 (CAG to CGG); a silent TC change at codon 343; and a silent
      GA transition at codon 1019. Leptin is related with obesity and its metabolic
      disorders. However, new relation ships have been described; inflammatory bowel
      disease, cancer, bone formation, asthma and so on. In conclusion, despite the
      great advances in our knowledge of leptin physiology, many areas of investigation
      remain. Future research is expected to discover new molecules in the leptin
      pathway, to treat obesity and its related diseases.

PMID- 19182740
TI  - Pattern of ocular trauma admitted in a tertiary hospital.
AB  - Ocular trauma is an important cause of ocular morbidity. This prospective study
      was conducted to identify primarily the population at risk, sources of eye
      injuries and the common barriers for their early management. Cases were selected
      randomly during the period Aug/2006 to March/2008 among the patients admitted in
      the department of ophthalmology, Mymensingh Medical College Hospital, with the
      history of ocular injury. A total of 100 eyes in 97 patients were included in the
      study. Age ranges were 1.5 years to 75 years. Male were 78.35% (n=76) & female
      were 21.65% (n=21). 56.00% (n=56) injuries were accidental occupational injuries.
      Common sources of eye injury included sharp objects used in occupational
      activities 43% (n=43), blunt objects 23% (n=23), Chemicals 7% (n=7), Projectile
      objects 8%, (n=8), Bird-beak 5% (n=5), agricultural trauma 3% (n=3) and
      miscellaneous 11% (n=11). Young adult males engaged in industrial, mechanical,
      agricultural or domestic works are at particular risk for ophthalmic trauma.
      Poverty, ignorance, indigenous treatment, remote communications and lack of
      supervised and collaborative management seems to be the possible barriers for the
      early management of ocular injuries. Preventive measures are recommended to adopt
      not only in the workplaces but also in domestic, recreational, sports and
      transport settings.

PMID- 19182741
TI  - Outcome of pregnancy in women 35 years of age and above.
AB  - Pregnancy outcome among women in the age group of 35 years and more are
      considered to be less favorable than those of younger women. To observe those,
      this case control study was conducted in the department of Obstetrics &
      Gynaecology, Mymensingh Medical College Hospital during the period of 1st June
      2003 to 31st May 2004. The study includes 100 patients of 35 years of age or
      above and 100 controls of 20-30 years of age. Observed complications during the
      pregnancy and delivery were increased incidence of placenta previa,
      malpresentation, intrauterine death, preterm labour, obstructed labour ruptured
      uterus etc. Pregnancy related complications were found significantly high
      (p<0.001) in case group (80%) compared to control group (51%). Rate of caesarian
      section was also more among the cases. Post delivery maternal complications were
      more in case group (53%) compared to control (30%) (p<0.001). Perinatal morbidity
      and mortality was significantly high. Cause of late fetal death in older women
      include, failure of the uterine vasculature in older women to adapt sufficiently
      to the increase haemodynamic demands of pregnancy, reduced fetal oxygenation with
      maternal age and also a rise in the frequency of preexisting hypertension with
      age. Maternal age is an important and independent risk in pregnancy outcome.

PMID- 19182742
TI  - Comparison between DOT EIA IgM and Widal Test as early diagnosis of typhoid
      fever.
AB  - A recently developed DOT enzyme immunoassay known as "Typhidot" for detecting IgM
      antibody against 50 KDa OMP antigen of Salmonella typhi, was evaluated on 100
      clinically suspected typhoid fever cases and 40 age-sex matched controls, in the
      Department of Microbiology, Mymensingh Medical College during, the period from
      June 2006 to July 2007. Blood culture, Widal test, and DOT EIA for IgM test were
      performed in all patients. Among 100 clinically suspected typhoid fever cases, 35
      were subsequently confirmed on the basis of positive blood culture for S. typhi
      and/or significant rising titre of Widal test. The DOT EIA IgM test could produce
      results within 1 hour. The result of the DOT EIA IgM test showed a good
      diagnostic value for typhoid fever. The sensitivity, specificity, positive and
      negative predictive value of the test was found as 91.42%, 90.00%, 88.88% and
      92.30% respectively. On the other hand corresponding values for Widal test were
      of 42.85%, 85.00%, 71.42% and 62.96% respectively. Thus, The DOT EIA IgM seems to
      be a practical alternative to Widal test for early diagnosis of typhoid fever.

PMID- 19182743
TI  - Anti H.pylori IgM in symptomatic and asymptomatic population.
AB  - To evaluate the usefulness of specific IgM in the diagnosis of Helicobacter
      pylori infection, a cross sectional study was carried out in the Department of
      Microbiology, Mymensingh Medical College between July 2006 to June 2007. A total
      of 45 patients having upper gastrointestinal symptoms underwent endoscopy and
      were subsequently diagnosed as patients with gastritis, peptic ulcer (PU) and non
      ulcer dyspepsia (NUD) and another 45 asymptomatic individuals aged 18-65 years,
      were included in the study. The serum samples of participants were tested for
      presence of anti-H pylori IgM by using ELISA method. The ELISA for anti H. pylori
      IgM provided sensitivity and specificity of 73.33%, 93.33% respectively.

PMID- 19182744
TI  - PCR for mecA gene of methicillin resistant Staphylococcus aureus.
AB  - The study was under taken to detect mecA gene of methicillin resistant
      Staphylococcus aureus (MRSA) by PCR. It was carried out in the department of
      Microbiology, Mymensingh Medical College in collaboration with the Department of
      Medicine under the Faculty of Veterinary Science, Bangladesh Agricultural
      University, Mymensingh between the periods from July 2006 to June 2007. A total
      of 40 S. aureus strains were used in this study. Isolates of S. aureus were
      identified by standard microbiology technique and their antimicrobial
      susceptibility test was done by disk diffusion method according to NCCLS. Minimum
      inhibitory concentration (MIC) of oxacillin was determined for all isolates by
      standard agar plate dilution method. All strains were tested for mecA gene by
      PCR. Out of 40 S. aureus strains 15(37.5%) were detected as MRSA by disk
      diffusion and agar dilution method but 10(25%) yielded mecA gene by PCR.
      Detection rate of MRSA by disk diffusion and agar dilution test showed
      significant difference to that by PCR (p<0.001).

PMID- 19182745
TI  - Association between morphological changes of nail and nail arsenic level in
      patients with arsenicosis.
AB  - This case-control type of analytical study was conducted in the Department of
      Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University, Dhaka,
      Bangladesh to find out the association between morphological changes of nail and
      nail arsenic level in arsenicosis patients. Majority of arsenicosis patients were
      male (56.67%). The mean age of the cases was 43.07+/-13.73 years. Nail changes
      were found in 26.67% of cases, most were nail dystrophy (23.33%) and rest were
      Mee's line (3.34%). There was significant difference between cases with or
      without nail changes and nail arsenic level. But cases with or with out nail
      changes had a significant difference between duration of intake of arsenic
      contaminated water. There was no correlation between nail changes and nail
      arsenic level for nail dystrophy and Mee's line. The study result failed to
      establish association between the morphological changes of nail and nail arsenic
      level.

PMID- 19182746
TI  - A study to evaluate the efficacy and safety of oral fluconazole in the treatment
      of tinea versicolor.
AB  - In our study of 6 month of pityriasis versicolor patient in skin department of
      Mymensingh Medical College Hospital outdoor, most of the patient was of age 16-25
      years (63.33%), 20% was of age 26-35 years and 16.67% was of 36-45 years. Age
      distribution among male patient maximum (66.67%) was of 16-25 years and among
      females the maximum 50% was also of 16-25 years. Mostly was male (80%) and 20%
      was female only 20% of the patient has got the positive family history whereas
      80% with no family history of the disease, which indicates that there is no
      hereditary predilection. Of the patient 66.67% was unmarried and 33.33% was
      married. Late adolescence & early adult age groups are predominantly affected.
      Small children & elderly adults are infected only in unusual circumstances, such
      as prolonged occlusion or immunosuppresion. Prevalence reported to be as high as
      50% in the humid, hot environment of Western Samoa & on low as 11.1% in the
      colder temperature of Sweden. About sex distribution of patients 20% were female.
      The study shows that majority of patients were male (20%).

PMID- 19182747
TI  - What is known to us about renal function of our retired peoples?
AB  - BACKGROUND: Bangladesh is one of the twenty countries in the world with the
      largest elderly populations, and by 2025, along with four other Asian countries,
      will account for 44% of world's total elderly population. This rapidly increasing
      population is a new and important group in terms of social and health policy in
      the country. As retired geriatric population is increasing day by day and there
      is a striking increase in their life expectancy and a decrease kidney function
      recognized as risk factor for morbidity and mortality in the elderly so
      evaluation of the renal function of retired persons are essential. OBJECTIVE: To
      assess the renal function of retired geriatric population by estimation of
      creatinine clearance by Cockcroft-Gault formula. DESIGN: This was a cross
      sectional study. PARTICIPANT: Retired persons aged 57 years and above without
      known hypertension, diabetes, renal diseases as study group and healthy adult
      aged 18-55 years as control group were included in this study. All were obtained
      from different areas of greater Mymensingh districts. INTERVENTION: Under strict
      aseptic precaution, venous blood was collected and serum creatinine of all were
      measured by deproteinization method and then calculation of creatinine clearance
      was done by using Cock-croft Gault formula. OUTCOME MEASURES: Serum Creatinine,
      Creatinine clearance. RESULT: Significant decrease of creatinine clearance was
      found in the study group (57 years and above) in comparison to control group
      (p<0.001). There is progressive decrease of creatinine clearance values by age.
      LIMITATION: Calculation of Creatinine clearance by Cock-croft formula is not
      unambiguous and still not accepted unanimously globally. The other tests of renal
      function were not done. CONCLUSION: Though the mean creatinine clearance values
      were significantly decreased in 57 years and above which was progressively
      decreased by age, yet values were within normal physiological limits. So the
      retired geriatric population has good renal function in our setting.

PMID- 19182748
TI  - Histological variant of nephrotic syndrome with atypical presentation in
      children.
AB  - Aims of the present study were to find out the histological pattern of atypically
      presenting nephrotic syndrome children and their response with oral
      corticosteroid therapy. This prospective study was carried out in the Paediatric
      Nephrology unit of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka,
      for a period of two years, from September 2001 to September 2003. Forty children
      with nephrotic syndrome with atypical presentations such as gross haematuria,
      renal impairment, hypertension and hypocomplementaemia were enrolled for the
      study. For each patient proper investigations were done to screen out infection
      and necessary treatment was given accordingly. Renal biopsy was done in all cases
      after treating infection and controlling hypertension and specimen were evaluated
      by light and immunofluorescence microscopy. All the patients were treated with
      oral prenisolone 60 mg/m2/day for 4 weeks and response were observed by heat
      coagulation test. In present study it was observed that mean age of presentation
      was 8.73+/-4.36 years. Hypertension, gross haematuria, impaired renal function
      and hypo-complementaemia were observed in 50%, 45%, 19% and 15% cases
      respectively. When histopathologies were considered, 90% cases had other than
      minimal change disease (MCD) and Mesangial proliferative glomerulonephritis
      (MesPGN) was the most common histopathology (47.5%). Regarding steroid therapy
      only 43.2% patients were responsive to oral prednisolone therapy within 28 days.
      Atypically presented nephrotic syndrome usually manifested with higher age of
      onset, gross haematuria, hypertension, renal insufficiency and
      hypocomplementaemia. Mesangial proliferative glomerulonephritis was the
      predominant histological type. The majority (56.8%) of these atypically presented
      nephrotic syndromes were resistant to steroid therapy.

PMID- 19182749
TI  - Central nervous system tuberculosis and adjuvant corticosteroid therapy.
AB  - Tuberculous involvement of central nervous system is one of the important health
      issues causing high mortality and morbidity. Uncertainty and doubt dominate all
      aspects of CNS tuberculosis. Diagnosis is mainly based on clinical features,
      cerebrospinal fluid changes, and imaging characteristics. Few studies have shown
      that corticosteroids improve the clinical outcome, although the precise mechanism
      of action remains tentative. All the cases were selected on strong clinical
      suspicion of CNS tuberculosis. They were graded according to tuberculous
      meningitis (TM) severity grades. In this connection, we studied 13 patients in
      one medicine unit over 12 month's period to see the effect of corticosteroid as
      part of the outcome. Nine patients (69.23%) were in grade II, three (23.08%)
      patients were in grade III, and one (7.69%) was in grade I. Seven patients
      (53.85%) had tuberculous meningitis and six (46.15%) had tuberculoma (CT or MRI).
      Out of 13 cases 3 patients (23%) died in the hospital and 10 patients (77%)
      improved, of whom 2 patients (20%) recovered completely and 8 patients (80%) had
      residual neurological deficit. Our study suggests that the early detection of CNS
      tuberculosis is the most important prognostic factor. Timely started anti-Koch's
      treatment with adjuvant corticosteroid therapy has a direct bearing on patient
      outcome.

PMID- 19182750
TI  - Association of pelvic tuberculosis with tubal factor infertility.
AB  - Tubal block is a common cause of infertility. Therefore Laparoscopy or
      Hysterosalphingoraphy or Hydrosonosalphingography are accepted methods for
      diagnosis of tubal block. Genital tuberculosis has a world wide distribution,
      more common in developing countries. Tubal block is the sequel of that disease.
      This prospective study by determination of Acid Fast Bacilli (AFB) in the
      endometrium of infertility patients was carried out in 60 patients at the
      Infertility unit, department of Obstetrics & Gynecology Bangabandhu Sheikh Mujib
      Medical University (BSMMU) during January 2005 to December 2006. In this study
      AFB positive in endometrium was in 14(46.7%) cases and 4(13.3%) in control. Out
      of 30 cases 60% had primary sub-fertility and 40% had secondary sub fertility.
      Most common tubal pathology was adhesion in 11(36%) cases. Others were beaded and
      tortuous in 8(26.7%) and hydrosalphix in 6(20%) and tube was dilated in 2(6.7%)
      cases. There were bilateral tubal block in 18(60%) and unilateral tubal block in
      12 (40%) cases.

PMID- 19182751
TI  - Role of micro-ESR and I/T ratio in the early diagnosis of neonatal sepsis.
AB  - This prospective study was undertaken in Dhaka Shishu Hospital from 15th March
      2005 to 15th October 2006 to determine the role of micro-ESR and immature and
      total neutrophil (I/T) ratio in early diagnosis of neonatal septicaemia. Eighty
      suspected cases of septicaemia admitted in neonatal ward of Dhaka Shishu Hospital
      were included in this study. Patients those who had history of perinatal
      asphyxia, infant of diabetic mother, congenital cyanotic heart disease etc. were
      excluded from the study. Thirty neonates without sign symptoms of septicaemia
      admitted for other causes like jaundice, feeding problems etc. were taken as a
      control group. After taking informed consent data were collected in structured
      questionnaire. Following hematological investigations like total WBC count,
      differential count, absolute neutrophil count, band cell count, platelet count,
      CRP, blood culture were done. Micro-ESR was done as bed side test. I/T ratio
      detected from total neutrophil and band form count. Patients with positive blood
      culture were categorized as definite sepsis. Patients with negative blood culture
      but abnormal hematological report suggestive of sepsis were categorized as
      probable sepsis. Those who had no signs of sepsis were categorized as control
      group. Micro-ESR more than age of the patient in days+3 mm in 1st hour were
      considered significant for sepsis. I/T ratio more than 0.2 was considered
      positive for sepsis. Sensitivity and specificity of micro-ESR was 63.3% and 60%
      respectively. Sensitivity and specificity of I/T ratio was 70% and 56%
      respectively. Combination of micro-ESR and I/T ratio showed high sensitivity
      (80%) and specificity (70%).

PMID- 19182752
TI  - Evaluation of 100 cases of ascites.
AB  - This has been a descriptive cross sectional study on 100 consecutive adult cases
      of ascites. They were studied regarding the incidence of underlying causes,
      variable clinical presentations and the co-relation of investigations with
      clinical features during the period of September, 2006 to August, 2007 in Sher-e
      Bangla Medical College Hospital, Barisal, Bangladesh. Diagnosis of ascites was
      based on history, clinical examination & USG examination. Among the 100 cases,
      male were 68 & female were 32, age range was 13-61 years. Causes of ascites were
      cirrhosis of liver 68%, tubercular peritonitis 9%, hepatocellular carcinoma 8%,
      congestive cardiac failure 6%, malignancy 4%, nephrotic syndrome 3%, lymphoma 2%
      and others 4%. Cirrhosis of liver is the major cause of ascites in our study.
      Many of the patients with cirrhosis & hepatocellular carcinoma were positive for
      HBsAg & anti HCV implying that hepatitis B & C viruses play a positive role in
      this condition.

PMID- 19182753
TI  - Quantitation of proteinuria in nephrotic syndrome by spot urine protein
      creatinine ratio estimation in children.
AB  - In Nephrotic Syndrome the amount of protein excretion is a reflection of activity
      of disease. Quantitative measurement of proteinuria by a 24-hour urine collection
      has been the accepted method of evaluation. Recent studies have shown that
      calculation of protein/creatinine ratio in a spot urine sample correlates well
      with the 24-hour urine protein (24-HUP) excretion. A study was conducted to
      compare the accuracy of a spot urinary protein/creatinine ratio (P/C ratio) and
      urinary dipstick with the 24-hour urine protein. Fifty two samples from 26
      patients of nephrotic syndrome were collected. This included a 24-hour urine
      sample followed by the next voided random spot sample. The protein/creatinine
      ratio was calculated and dipstick was performed on the spot sample. This was
      compared with the 24-hour urine protein excretion. The correlation between the
      three samples was statistically highly significant (p<0.001) for all levels of
      proteinuria. The normal value of protein/creatinine ratio in Indian children was
      also estimated on 50 normal children admitted in the ward without any renal
      diseases calculated to be 0.053 (SE of mean+/-0.003).

PMID- 19182754
TI  - Anti phospholipid syndrome.
AB  - Anti Phospholipid Syndrome (APS) is a relatively new conception of syndrome
      complex first noticed in 1983. It may be primary or secondary to other diseases
      like SLE, RA, Systemic sclerosis, behchet's syndrome, temporal arteritis,
      sjogren's syndrome psoriatic arthropathy etc. Clinical manifestations are
      consequences of vascular thrombosis and embolism like DVT, pulmonary embolism,
      stroke, TIA, complication of pregnancy with pregnancy loss. We report a 34 years
      married female housewife who presented with sudden onset of nausea, vomiting,
      vertigo, dysphagia, dysarthria and ataxia. She had a chronic leg ulcer.
      Neurological findings were consistent with lateral medullary syndrome due to
      stroke though she was normotensive, nondiabetic with normal lipid profile. She
      had history of two abortions in last three years. Investigations were done
      accordingly and she fulfilled the diagnostic criteria of APS. No secondary cause
      was detected after thorough clinical examination and laboratory investigations.
      She was treated symptomatically along with oral anticoagulation. She improved
      slowly but steadily.

PMID- 19182755
TI  - Kartagener's Syndrome.
AB  - Kartagener's Syndrome or Immotile Cilia Syndrome, a variant of Primary Ciliary
      Dyskinesia (PCD), is a rare autosomal recessive genetic disorder caused by defect
      in the tiny hair like structure, the cilia lining the respiratory tract (upper
      and lower), sinuses, eustachian tubes, middle ear and fallopian tubes. Here
      electron microscopy shows abnormal arrangement of ciliary tubules and patients
      with Kartagener's syndrome has an absence of dynein arms at the base of the
      cilia. The inability of cilia to move results in inadequate clearance of bacteria
      from the air passages, resulting in an increased risk of infection and causing
      bronchiectasis. Another result of ciliary immobility is infertility. A 60 years
      old lady was diagnosed as a case of Kartagener's syndrome. She had history of
      chronic cough for 20 years, irregular fever for 20 years and occasional shortness
      of breath for 5 years. Relevant investigations revealed dextrocardia, situs
      inversus, bilateral maxillary sinusitis with non pneumatised frontal sinus and
      bronchiectasis. She was treated with low concentration oxygen inhalation,
      antibiotic, bronchodilator, chest physiotherapy including postural drainage,
      vitamins and other supportive treatment.

PMID- 19182756
TI  - Bardet-Biedl syndrome.
AB  - A young boy of 9 years hailing from Fulpur, Mymensingh was admitted in the
      department of Ophthalmology, Mymensingh Medical College Hospital, Mymensingh,
      Bangladesh on the 26th November, 2007 with the complaints of dimness of vision of
      both the eyes and night blindness since birth. The boy suffered poor mental
      performances with delayed mild stone development. He was apathetic looking and
      below average IQ with short stature. Visual acuity of this patient recorded 6/60
      both the eyes with nystagmus. Fundus examination revealed waxy disc atrophy,
      arteriolar attenuation and retinal degeneration both the eyes. He had
      polydactilism, trunkal obesity, hypogenitalism. On the basis of history, clinical
      examination and relevant investigations the patient was diagnosed as Bardet-Biedl
      Syndrome.

PMID- 19182757
TI  - Proliferative glomerulonephritis with acute renal failure-a rare manifestation in
      seronegative rheumatoid arthritis.
AB  - A 55 years old lady with advanced rheumatoid arthritis (RA) presented with severe
      acute renal failure with significant proteinuria preceded by fever for 14 days.
      She had no history of taking drugs usually responsible for glomerulonephritis,
      neither had she any clinico-biochemical evidence of peri-infectious
      glomerulonephritis. Acute interstitial nephritis (AIN) was excluded by absence of
      eosinophilia and eosinophils in urine. Renal biopsy reveled absence of
      amyloidosis and showed Focal segmental proliferative glomerulonephritis (FSGN).
      Patient was successfully managed with methyl-prednisolone followed by steroid and
      immunosuppressive and patient came over renal failure. So FSGN should be
      considered as one of the causes of acute renal failure in a patient with
      seronegative RA which may respond to immune-therapy like rapidly progressive
      glomerulonephritis.

PMID- 19182758
TI  - Extensive skeletal lesions in childhood acute lymphoblastic leukemia.
AB  - A 2 years old male child was admitted in Dhaka Shishu Hospital with one month
      history of fever, swelling and pain in joints of right leg. Hematological and
      microbiological investigation revealed normal except radiological findings when
      there were destructive lesions of affected bones and thought to be Langerhan's
      cell histiocytosis but did not respond to treatment. Subsequently, he was
      transfer to Pediatric Hematology and Oncology, Bangabandhu Sheikh Mujib Medical
      University (BSMMU) for proper management. On examination, the boy was mildly
      pale, severe bone pain, no organomegaly but few occipital group of lymphnode were
      palpable. He had extensive red tender swelling over the hands and legs.
      Hematological values showed high WBC, low platelet count and lymphoblasts.
      Biochemical values were high serum LDH and serum uric acid. Skeletal survey
      showed diffuse osteolytic lesion and osteoporosis with evidence of transverse
      metaphyseal radiolucent bands (leukemic line), lamellar periosteal reactions and
      cortical erosions widespread throughout the skeleton with subperiosteal new bone
      formation. Radioisotop of skeleton showed increase uptake at the site of lesions.
      Bone marrow aspiration findings were suggestive of ALL-L1 and cytochemistry of
      aspirate showed PAS positive and Sudan black negative. Immunophenotype confirmed
      as pre-B ALL, Then, protocol based induction had given for 4 weeks. Thereafter, a
      short course of intensification followed by maintenance therapy had started with
      significant improvement of physical, hematological and radiological findings. So,
      an awareness of varied clinical and radiological manifestations of childhood ALL
      in bone marrow and skeletal system are needed in order to establish a correct
      diagnosis when the presenting signs and symptoms are enigmatic. It is also
      important to keep in mind the possibility of extensive skeletal involvement in
      ALL, especially when a child present with pain, swelling of limb with walking
      difficulties. The curability of ALL in contrast to metastatic malignancies makes
      accurate diagnosis of paramount importance.

PMID- 19182759
TI  - Kikuchi-Fujimoto disease.
AB  - A 14 year-old Bangladeshi girl presented with high fever, painful swellings in
      the neck, anorexia, weight loss and night sweating. On examination she had
      multiple enlarged and tender cervical lymph nodes. Other systems were normal.
      Laboratory investigations for sepsis and autoimmune diseases were negative.
      Initial fine needle aspiration and cytology of affected lymph node was suggestive
      of tubercular lymphdenitis. But she did not respond to anti-tubercular treatment.
      Kikuchi-Fujimoto disease was diagnosed from the histopathological appearance of
      excised lymph node. She completely recovered with symptomatic treatment. Kikuchi
      Fujimoto disease, also called Kikuchi's disease or histiocytic necrotizing
      lymphadenitis is a rare, benign but enigmatic disease of unknown aetiology. The
      disease is self-limited and has an excellent prognosis. Its recognition is
      crucial because it can be mistaken for systemic lupus erythematosus, malignant
      lymphoma, tubercular lymphadenitis or even, for metastatic adenocarcinoma.
      Clinicians' and pathologists' awareness of this disease may help prevent
      misdiagnosis and inappropriate treatment.

PMID- 19182760
TI  - Upper abdominal mass with diagnostic dilemma.
AB  - A 32 years old gentleman presented with a lump occupying the epigastric, left
      hypochondriac and umbilical region for the last 3 months which gradually
      increased in size & dull aching pain. He also complained of low grade fever and
      early satiety. On examination, he had a lump on upper abdomen which was
      irregular, firm, mildly tender, lobulated surface, restricted mobility, dull on
      percussion. USG examination of HBS revealed hepatomegaly and SOL in liver. CT
      abdomen revealed soft tissue mass in left upper abdomen. FNA revealed cells of
      mesenchymal origin. Per operatively a large lobulated, myxomatous highly vascular
      mass arising from the fundal part of the stomach was found and removed.
      Histopathology report comments about two differential diagnosis-leiomyosarcoma
      and gastrointestinal stromal tumour. CD117 immunostaining confirmed it was
      gastrointestinal stromal tumor (GIST). Post operatively patient was treated by
      Imatinib and is now under regular follow up.

PMID- 19182761
TI  - Patient with bilateral breast enlargement and hypospadias.
AB  - A 20 year old man was admitted in the surgical unit of Dhaka Medical College
      Hospital on August 2007 presented with Hypospadias & underdeveloped penis from
      childhood, gradual enlargement of both breasts for the last 10 years, absence of
      axillary and pubic hair from puberty & painful swelling of both testes for the
      last 3 years. The patient was regarded as a female upto the age of 10 years. He
      has got no voice change since puberty. On examination he had average body built,
      there was bilateral gynaecomastia, hypospadias, rudimentary penis & absence of
      pubic and axillary hair. His testosterone level, serum prolactin level, serum
      progesterone level, serum estradiol level was done. Cytology on buccal smear done
      and ultrasonography revealed no ovary and uterus. Ultimately patient was
      diagnosed as a case of androgen insensitivity syndrome (AIS). The case is
      reported for clinical awareness & to share our experience.

PMID- 19182762
TI  - Multifocal skeletal tuberculosis in children.
AB  - Multifocal bone involvement is though rare but is reported from some countries
      where tuberculosis is endemic. Here we report a case of three years old boy was
      admitted in Bangabandhu Sheikh Mujib Medical University, Dhaka with the
      complaints of difficulty in walking ,low grade fever for six months, swelling
      over the back, elbow joint, knee joint and upper part of forearm and legs for two
      months. Family history of tuberculosis was positive. Mantoux test was 18 mm, ESR
      85 mm in first hour, chest X-ray reveals right hilar lymphadenopathy, X-ray
      dorsolumber spine shows wedge shaped deformity in T11, L4 and with paravertebral
      collection from L2-L4. X-ray of legs, knee joint and forearms show multiple lytic
      lesions in shaft with periosteal reaction and cortical thickening. Ultrasonograph
      of whole abdomen shows psoas abscess. Culture of bone marrow aspirate reveals
      Mycobacterium tuberculosis. Patient was given an anti tubercular regimen with
      Rifampicin, Isoniazid, Pyrazinamide and Streptomycin for initial two months which
      to be followed by Rifampicin and Isoniazid for another 10 months.

PMID- 19182763
TI  - Incretin mimetics and DPP-4 inhibitors: new approach to treatment of type 2
      diabetes mellitus.
AB  - Type 2 diabetes constitutes the main bulk (85-90%) of diabetic population. It is
      a chronic metabolic disorder with progressive ?beta-cell dysfunction, impaired
      insulin actions and various other abnormalities. Insulin response of beta-cell is
      more after oral glucose or following meal than intravenous infusion of glucose.
      Gut related peptides, the incretin hormones released after meal following
      activation of the enteroinsular axis plays an important role in glucose
      homeostasis by pancreatic and extrapancreatic glucoregulatory effects and helps
      in preservation of beta-cell function. In type 2 diabetes, there is progressive
      decline of these incretins level, glucagons like peptide-1 (GLP-1) and glucose
      dependent insulinotropic polypeptide (GIP) with loss of beta-cell mass, beta-cell
      function and glycemic deterioration. These peptides are rapidly degraded by
      endogenous proteases, dipeptidyl peptides-4 (DPP-4) giving a very short half life
      of 2-3 minutes. Currently available anti-diabetic drugs do not address these arms
      of glucoregulatory dysfunction of type 2 diabetes. Modern therapeutic strategy
      should be targeted at preservation of beta-cell mass and function by exploiting
      the incretin hormones and enteroinsular axis. DPP-4 resistant incretin
      analogues/mimetics (e.g. exenatide, liraglutide) that have been developed by
      modifications/ substitutions in the polypeptide chain may be an effective
      alternative of the existing therapy of type-2 DM. DPP-4 inhibitors (e.g.
      sitagliptin, vindagliptin) prevent the degradation of endogenous GLP-1 and GIP,
      thereby potentiate their actions and help in glycemic control. Distinctive
      features of incretin mimetics are: their action is glucose dependent, do not
      produce hypoglycemia, help in preservation of beta-cell mass and function, help
      in weight reduction. DPP-4 inhibitors are weight neutral. Ongoing studies will
      reveal newer avenues and long term outcome of these molecules.

PMID- 19182764
TI  - Effect of zinc on growth of preterm babies.
AB  - Zinc is being recognized increasingly as an important element in human growth,
      development and immunological function. It is probably the most intensely studied
      microelement in newborn nutrition. Zinc deficiency is common in young infants in
      the developing world and is associated with reduced immunocompetence and
      increased rates of serious disease. Preterm neonates are especially vulnerable
      because of preterm delivery and low birth weight. The preterm baby has very
      limited stored energy and needs an adequate supply of nutrient. Preterm infant
      have high zinc dietary requirements as 60% fetal zinc is acquired during third
      trimester of pregnancy. Low concentration of zinc was found in pre-term low birth
      weight babies in different studies. Studies showed that before supplementation
      serum zinc level in preterm low birth weight babies were 62+/-12.4 microgm/dl, 65
      microgm/dl, 54+/-14.4 microgm/dl and after supplementation serum zinc level were
      105.8+/-16.6 microgm/dl, 86.4+/-24.7 microgm/dl respectively. At the same time
      mean weight & length of supplementation and without supplementation group were
      6084 gm vs. 5280 gm, 2779+/-638.7 gm vs. 2474.6+/-441.8 gm and length 23.7 cm vs.
      21.4 cm, 46.49+/-2.6 cm vs. 44.1+/-2.8 cm respectively. So supplementation of
      zinc in preterm babies causes improved growth and development. Various reports
      showed beneficial effect of long supplement in early growth of pre-term babies.
      However long term follow up studies are needed to evaluate the beneficial effect
      of zinc supplementation on growth of preterm babies.

PMID- 19182765
TI  - Prismatic correction of residual esotropia of 20 prism dioptres or less after
      full hypermetropic correction.
AB  - PURPOSE: To assess the efficacy of prismatic correction of residual esotropia
      <or=20 prism dioptres (PD) after full hypermetropic correction in patients with
      partially accommodative esotropia. METHODS: Medical records of 64 patients who
      received prismatic correction for residual esotropia </=20 PD were reviewed.
      Outcomes were considered successful if patients maintained orthotropia or
      esophoria for at least 1 year and did not require surgery. Factors including age,
      sex, visual acuity, refractive errors, amount of deviation, sensory status, and
      the presence of amblyopia were analysed and compared between the success and
      failure groups. RESULTS: Prismatic correction was successful in 28 of 64 patients
      (44%). The success group showed better results both with Worth 4-dot test
      (P=0.001 at distance and P=0.046 at near) and Randot stereo test (P=0.003 for
      dots and P=0.000 for animals). Success rate increased to 58% without amblyopia,
      72 and 93% with normal fusional response at near and at distance with Worth 4 dot
      test respectively, and 92% with stereoacuity of 800 s of arc or better. In all
      patients in success group, fusion and stereoacuity improved or maintained during
      follow-up. CONCLUSIONS: Prismatic correction was successful in 44% of the
      patients with residual esotropia <or=20 PD and the success group showed an
      improved or stable sensory status with time. With a baseline fusion on Worth 4
      dot test or stereopsis of 800 s of arc or better, prismatic correction could be
      considered as the first-line treatment.

PMID- 19182766
TI  - Infantile nystagmus and late onset ataxia associated with a CACNA1A mutation in
      the intracellular loop between s4 and s5 of domain 3.
AB  - PURPOSE: Mutations in the 1A-subunit of the brain P/Q-type calcium channel gene
      CACNA1A are responsible for spinocerebellar ataxia type 6 (SCA6), familial
      haemiplegic migraine (FHM) and episodic ataxia type 2 (EA2). Considerable
      clinical and genetic overlap exists between these 3 allelic disorders. Clinical
      findings are varied and may include nystagmus. OBJECTIVE: To study the clinical
      phenotype and identify a causative mutation in a family who presented when the
      youngest member was diagnosed with apparent isolated congenital nystagmus (age 3
      months). PATIENTS AND METHODS: 8 patients from one family underwent detailed
      clinical phenotyping comprising; ophthalmic and neurological examination,
      nystagmology, electrodiagnostic tests and brain imaging. The CACNA1A gene was
      screened for mutations by direct sequencing in one patient. Co-segregation of the
      disease and an identified sequence variation was shown using direct sequencing.
      RESULTS: Phenotyping revealed isolated atypical nystagmus in 4 family members and
      nystagmus in addition to late onset ataxia in 1 family member. Direct sequencing
      of the CACNA1A gene identified a novel missense mutation; (c.4110T>G p.Phe1370Leu
      (NM_000068.3)). CONCLUSIONS: We have shown that a mutation in the intracellular
      domain between s4 and s5 of repeat 3 can cause atypical nystagmus/cerebellar
      phenotypes, including isolated nystagmus in an infant. We also illustrate the
      necessity for detailed examination of relatives in cases of apparent isolated
      congenital nystagmus.

PMID- 19182767
TI  - Topical prostaglandin analogues do not affect selective laser trabeculoplasty
      outcomes.
AB  - PURPOSE: To investigate the effect of topical prostaglandin analogue use on the
      efficacy of selective laser trabeculoplasty (SLT) intraocular pressure (IOP)
      lowering in patients with open-angle glaucoma. PATIENTS AND METHODS: This
      retrospective study included 123 consecutive patients who underwent 180 degrees
      SLT for the first time. Eyes were grouped into those that received prostaglandin
      analogues before and after SLT (n=74) and those that did not (n=49). The main
      outcome measure was IOP lowering after SLT. Success was defined as > or =20%
      reduction in IOP without further glaucoma intervention. RESULTS: There was no
      significant difference in IOP lowering at 6 months post-laser between the
      prostaglandin and non-prostaglandin groups (3.9+/-4.8 vs 4.6+/-3.6 mm Hg,
      P=0.43). Long-term SLT success rates were also not significantly different
      between the treatment groups (Kaplan-Meier survival analysis, P=0.68). IOP
      lowering at 6 months was similar in eyes that received no glaucoma medications,
      monotherapy with or without a prostaglandin analogue, or combination therapy with
      or without prostaglandin analogues (P=0.81). Logistic regression analysis showed
      that various patient characteristics including age, sex, type of glaucoma,
      previous glaucoma surgery, and other glaucoma risk factors did not predict a
      successful SLT outcome. However, higher pre-operative IOP was found to predict
      SLT success (odds ratio=1.12, 95% CI=1.02-1.24, P=0.02). CONCLUSION: The IOP
      lowering efficacy of SLT is not influenced by the use of topical prostaglandin
      analogues.

PMID- 19182768
TI  - Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial
      dystrophy: review of the first 50 consecutive cases.
AB  - PURPOSE: To evaluate the clinical outcome and complications of Descemet membrane
      endothelial keratoplasty (DMEK), using Descemet-stripping endothelial
      keratoplasty (DSEK) as a back-up procedure, in the management of Fuchs
      endothelial dystrophy. DESIGN: Non-randomised prospective clinical study.
      METHODS: The first fifty consecutive eyes that underwent DMEK, that is,
      transplantation of an isolated donor Descemet membrane carrying its endothelium,
      for Fuchs endothelial dystrophy were evaluated. In all eyes, the best-corrected
      visual acuity (BCVA) as well as the endothelial cell density (ECD) was measured
      before and at 6 months after surgery, as clinical outcome parameters. RESULTS:
      Ten patients required a secondary DSEK for failed DMEK. In the remaining 40 DMEK
      eyes, 95% had a BCVA of > or = 20/40 (> or = 0.5) and 75% > or = 20/25 (> or =
      0.8) at 6 months after surgery. ECD averaged 2618 (+ or - 201) cells/mm(2)
      before, and 1876 (+ or - 522) cells/mm(2) at 6 months after surgery (n = 35).
      When the outcomes of DMEK and secondary DSEK procedures were combined, 94%
      reached a BCVA of > or = 20/40 (> or = 0.5) and 66% > or = 20/25 (> or = 0.8) (n
      = 47), and ECD averaged 2623 (+ or - 193) cells/mm(2) before, and 1815 (+ or -
      578) cells/mm(2) at 6 months after surgery (n = 43). CONCLUSION: With DSEK as a
      back-up procedure, DMEK may provide relatively quick and complete visual
      rehabilitation in a majority of patients operated on for Fuchs endothelial
      dystrophy. Endothelial cell survival may be similar to earlier types of
      (lamellar) keratoplasty. Early graft detachment was the main complication in this
      first series of DMEK surgeries for Fuchs endothelial dystrophy.

PMID- 19182770
TI  - Benefits of early awareness in age-related macular degeneration.

PMID- 19182771
TI  - Craniofacial fibrous dysplasia: clinical characteristics and long-term outcomes.
AB  - AIM: To present the clinical features and management outcomes in a large
      longitudinal series of patients with craniofacial fibrous dysplasia (CFD).
      METHODS: Retrospective interventional consecutive case series. Main outcome
      measures included signs and symptoms, radiographic findings, long-term outcomes,
      and postoperative complications. RESULTS: A total of 42 patients with CFD were
      identified. The mean age at presentation was 16.7 years; mean follow-up was 12.6
      years. Out of these 42 patients, 37 (88.1%) had unilateral involvement and 5
      (11.9%) had bilateral involvement, of which 3 (7.1%) had McCune-Albright
      syndrome. The commonest presenting symptom was facial asymmetry (36 cases, 86%).
      The frontal bone was the most commonly involved (27 cases, 64.3%), zfollowed by
      the sphenoid (24 cases, 57.1%). The most common pattern of bone involvement was
      monostotic (32 cases, 76.2%). Radiological optic canal involvement occurred in 18
      eyes of 15 (37.5%) patients, with optic atrophy in 9 eyes (18.8%) of 7 patients
      (16.7%). Surgical intervention was performed in 30 (71.4%) cases for both
      functional and reconstructive reasons. Optic canal decompression was performed in
      three cases, in all of which stabilization of vision was achieved; no patient
      lost vision as a result of surgery. CONCLUSIONS: In this large longitudinal
      series of CFD, visual loss was not uncommon and occurred insidiously. The
      presenting clinical and radiological features, surgical interventions, and
      outcomes are discussed.

PMID- 19182772
TI  - Ionic high-pressure form of elemental boron.
AB  - Boron is an element of fascinating chemical complexity. Controversies have
      shrouded this element since its discovery was announced in 1808: the new
      'element' turned out to be a compound containing less than 60-70% of boron, and
      it was not until 1909 that 99% pure boron was obtained. And although we now know
      of at least 16 polymorphs, the stable phase of boron is not yet experimentally
      established even at ambient conditions. Boron's complexities arise from
      frustration: situated between metals and insulators in the periodic table, boron
      has only three valence electrons, which would favour metallicity, but they are
      sufficiently localized that insulating states emerge. However, this subtle
      balance between metallic and insulating states is easily shifted by pressure,
      temperature and impurities. Here we report the results of high-pressure
      experiments and ab initio evolutionary crystal structure predictions that explore
      the structural stability of boron under pressure and, strikingly, reveal a
      partially ionic high-pressure boron phase. This new phase is stable between 19
      and 89 GPa, can be quenched to ambient conditions, and has a hitherto unknown
      structure (space group Pnnm, 28 atoms in the unit cell) consisting of icosahedral
      B(12) clusters and B(2) pairs in a NaCl-type arrangement. We find that the
      ionicity of the phase affects its electronic bandgap, infrared adsorption and
      dielectric constants, and that it arises from the different electronic properties
      of the B(2) pairs and B(12) clusters and the resultant charge transfer between
      them.

PMID- 19182773
TI  - Human occludin is a hepatitis C virus entry factor required for infection of
      mouse cells.
AB  - Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. The
      development of much needed specific antiviral therapies and an effective vaccine
      has been hampered by the lack of a convenient small animal model. The
      determinants restricting HCV tropism to human and chimpanzee hosts are unknown.
      Replication of the viral RNA has been demonstrated in mouse cells, but these
      cells are not infectable with either lentiviral particles bearing HCV
      glycoproteins (HCVpp) or HCV produced in cell culture (HCVcc) (A.P., M.E. and
      C.M.R., unpublished observations), suggesting that there is a block at the level
      of entry. Here we show, using an iterative complementary DNA library screening
      approach, that human occludin (OCLN) is an essential HCV cell entry factor that
      is able to render murine cells infectable with HCVpp. Similarly, OCLN is required
      for the HCV-susceptibility of human cells, because its overexpression in
      uninfectable cells specifically enhanced HCVpp uptake, whereas its silencing in
      permissive cells impaired both HCVpp and HCVcc infection. In addition to OCLN,
      HCVpp infection of murine cells required expression of the previously identified
      HCV entry factors CD81 (ref. 4), scavenger receptor class B type I (SR-BI, also
      known as SCARB1) and claudin-1 (CLDN1). Although the mouse versions of SR-BI and
      CLDN1 function at least as well as the human proteins in promoting HCV entry,
      both OCLN and CD81 must be of human origin to allow efficient infection. The
      species-specific determinants of OCLN were mapped to its second extracellular
      loop. The identification of OCLN as a new HCV entry factor further highlights the
      importance of the tight junction complex in the viral entry process, and provides
      an important advance towards efforts to develop small animal models for HCV.

PMID- 19182774
TI  - The haemangioblast generates haematopoietic cells through a haemogenic
      endothelium stage.
AB  - It has been proposed that during embryonic development haematopoietic cells arise
      from a mesodermal progenitor with both endothelial and haematopoietic potential
      called the haemangioblast. A conflicting theory instead associates the first
      haematopoietic cells with a phenotypically differentiated endothelial cell that
      has haematopoietic potential (that is, a haemogenic endothelium). Support for the
      haemangioblast concept was initially provided by the identification during mouse
      embryonic stem cell differentiation of a clonal precursor, the blast colony
      forming cell (BL-CFC), which gives rise to blast colonies with both endothelial
      and haematopoietic components. Although recent studies have now provided evidence
      for the presence of this bipotential precursor in vivo, the precise mechanism for
      generation of haematopoietic cells from the haemangioblast still remains
      completely unknown. Here we demonstrate that the haemangioblast generates
      haematopoietic cells through the formation of a haemogenic endothelium
      intermediate, providing the first direct link between these two precursor
      populations. The cell population containing the haemogenic endothelium is
      transiently generated during BL-CFC development. This cell population is also
      present in gastrulating mouse embryos and generates haematopoietic cells on
      further culture. At the molecular level, we demonstrate that the transcription
      factor Tal1 (also known as Scl; ref. 10) is indispensable for the establishment
      of this haemogenic endothelium population whereas the core binding factor Runx1
      (also known as AML1; ref. 11) is critical for generation of definitive
      haematopoietic cells from haemogenic endothelium. Together our results merge the
      two a priori conflicting theories on the origin of haematopoietic development
      into a single linear developmental process.

PMID- 19182775
TI  - Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control
      T(H)2 responses.
AB  - In the course of infection or autoimmunity, particular transcription factors
      orchestrate the differentiation of T(H)1, T(H)2 or T(H)17 effector cells, the
      responses of which are limited by a distinct lineage of suppressive regulatory T
      cells (T(reg)). T(reg) cell differentiation and function are guided by the
      transcription factor Foxp3, and their deficiency due to mutations in Foxp3
      results in aggressive fatal autoimmune disease associated with sharply augmented
      T(H)1 and T(H)2 cytokine production. Recent studies suggested that Foxp3
      regulates the bulk of the Foxp3-dependent transcriptional program indirectly
      through a set of transcriptional regulators serving as direct Foxp3 targets. Here
      we show that in mouse T(reg) cells, high amounts of interferon regulatory factor
      4 (IRF4), a transcription factor essential for T(H)2 effector cell
      differentiation, is dependent on Foxp3 expression. We proposed that IRF4
      expression endows T(reg) cells with the ability to suppress T(H)2 responses.
      Indeed, ablation of a conditional Irf4 allele in T(reg) cells resulted in
      selective dysregulation of T(H)2 responses, IL4-dependent immunoglobulin isotype
      production, and tissue lesions with pronounced plasma cell infiltration, in
      contrast to the mononuclear-cell-dominated pathology typical of mice lacking
      T(reg) cells. Our results indicate that T(reg) cells use components of the
      transcriptional machinery, promoting a particular type of effector CD4(+) T cell
      differentiation, to efficiently restrain the corresponding type of the immune
      response.

PMID- 19182776
TI  - Organ regeneration does not require a functional stem cell niche in plants.
AB  - Plants rely on the maintenance of stem cell niches at their apices for the
      continuous growth of roots and shoots. However, although the developmental
      plasticity of plant cells has been demonstrated, it is not known whether the stem
      cell niche is required for organogenesis. Here we explore the capacity of a broad
      range of differentiating cells to regenerate an organ without the activity of a
      stem cell niche. Using a root-tip regeneration system in Arabidopsis thaliana to
      track the molecular and functional recovery of cell fates, we show that re
      specification of lost cell identities begins within hours of excision and that
      the function of specialized cells is restored within one day. Critically,
      regeneration proceeds in plants with mutations that fail to maintain the stem
      cell niche. These results show that stem-cell-like properties that mediate
      complete organ regeneration are dispersed in plant meristems and are not
      restricted to niches, which nonetheless seem to be necessary for indeterminate
      growth. This regenerative reprogramming of an entire organ without transition to
      a stereotypical stem cell environment has intriguing parallels to recent reports
      of induced transdifferentiation of specific cell types in the adult organs of
      animals.

PMID- 19182777
TI  - Complete but curtailed T-cell response to very low-affinity antigen.
AB  - After an infection, T cells that carry the CD8 marker are activated and undergo a
      characteristic kinetic sequence of rapid expansion, subsequent contraction and
      formation of memory cells. The pool of naive T-cell clones is diverse and
      contains cells bearing T-cell antigen receptors (TCRs) that differ in their
      affinity for the same antigen. How these differences in affinity affect the
      function and the response kinetics of individual T-cell clones was previously
      unknown. Here we show that during the in vivo response to microbial infection,
      even very weak TCR-ligand interactions are sufficient to activate naive T cells,
      induce rapid initial proliferation and generate effector and memory cells. The
      strength of the TCR-ligand interaction critically affects when expansion stops,
      when the cells exit lymphoid organs and when contraction begins; that is,
      strongly stimulated T cells contract and exit lymphoid organs later than weakly
      stimulated cells. Our data challenge the prevailing view that strong TCR ligation
      is a prerequisite for CD8(+) T-cell activation. Instead, very weak interactions
      are sufficient for activation, but strong TCR ligation is required to sustain T
      cell expansion. We propose that in response to microbial challenge, T-cell clones
      with a broad range of avidities for foreign ligands are initially recruited, and
      that the pool of T cells subsequently matures in affinity owing to the more
      prolonged expansion of high-affinity T-cell clones.

PMID- 19182778
TI  - A single regulatory gene is sufficient to alter bacterial host range.
AB  - Microbial symbioses are essential for the normal development and growth of
      animals. Often, symbionts must be acquired from the environment during each
      generation, and identification of the relevant symbiotic partner against a myriad
      of unwanted relationships is a formidable task. Although examples of this
      specificity are well-documented, the genetic mechanisms governing it are poorly
      characterized. Here we show that the two-component sensor kinase RscS is
      necessary and sufficient for conferring efficient colonization of Euprymna
      scolopes squid by bioluminescent Vibrio fischeri from the North Pacific Ocean. In
      the squid symbiont V. fischeri ES114, RscS controls light-organ colonization by
      inducing the Syp exopolysaccharide, a mediator of biofilm formation during
      initial infection. A genome-level comparison revealed that rscS, although present
      in squid symbionts, is absent from the fish symbiont V. fischeri MJ11. We found
      that heterologous expression of RscS in strain MJ11 conferred the ability to
      colonize E. scolopes in a manner comparable to that of natural squid isolates.
      Furthermore, phylogenetic analyses support an important role for rscS in the
      evolution of the squid symbiosis. Our results demonstrate that a regulatory gene
      can alter the host range of animal-associated bacteria. We show that, by encoding
      a regulator and not an effector that interacts directly with the host, a single
      gene can contribute to the evolution of host specificity by switching 'on' pre
      existing capabilities for interaction with animal tissue.

PMID- 19182779
TI  - Transmembrane passage of hydrophobic compounds through a protein channel wall.
AB  - Membrane proteins that transport hydrophobic compounds have important roles in
      multi-drug resistance and can cause a number of diseases, underscoring the
      importance of protein-mediated transport of hydrophobic compounds. Hydrophobic
      compounds readily partition into regular membrane lipid bilayers, and their
      transport through an aqueous protein channel is energetically unfavourable.
      Alternative transport models involving acquisition from the lipid bilayer by
      lateral diffusion have been proposed for hydrophobic substrates. So far, all
      transport proteins for which a lateral diffusion mechanism has been proposed
      function as efflux pumps. Here we present the first example of a lateral
      diffusion mechanism for the uptake of hydrophobic substrates by the Escherichia
      coli outer membrane long-chain fatty acid transporter FadL. A FadL mutant in
      which a lateral opening in the barrel wall is constricted, but which is otherwise
      structurally identical to wild-type FadL, does not transport substrates. A
      crystal structure of FadL from Pseudomonas aeruginosa shows that the opening in
      the wall of the beta-barrel is conserved and delineates a long, hydrophobic
      tunnel that could mediate substrate passage from the extracellular environment,
      through the polar lipopolysaccharide layer and, by means of the lateral opening
      in the barrel wall, into the lipid bilayer from where the substrate can diffuse
      into the periplasm. Because FadL homologues are found in pathogenic and
      biodegrading bacteria, our results have implications for combating bacterial
      infections and bioremediating xenobiotics in the environment.

PMID- 19182780
TI  - Chromatin signature reveals over a thousand highly conserved large non-coding
      RNAs in mammals.
AB  - There is growing recognition that mammalian cells produce many thousands of large
      intergenic transcripts. However, the functional significance of these transcripts
      has been particularly controversial. Although there are some well-characterized
      examples, most (>95%) show little evidence of evolutionary conservation and have
      been suggested to represent transcriptional noise. Here we report a new approach
      to identifying large non-coding RNAs using chromatin-state maps to discover
      discrete transcriptional units intervening known protein-coding loci. Our
      approach identified approximately 1,600 large multi-exonic RNAs across four mouse
      cell types. In sharp contrast to previous collections, these large intervening
      non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci,
      exonic sequences and promoter regions, with greater than 95% showing clear
      evolutionary conservation. We also developed a functional genomics approach that
      assigns putative functions to each lincRNA, demonstrating a diverse range of
      roles for lincRNAs in processes from embryonic stem cell pluripotency to cell
      proliferation. We obtained independent functional validation for the predictions
      for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate
      that specific lincRNAs are transcriptionally regulated by key transcription
      factors in these processes such as p53, NFkappaB, Sox2, Oct4 (also known as
      Pou5f1) and Nanog. Together, these results define a unique collection of
      functional lincRNAs that are highly conserved and implicated in diverse
      biological processes.

PMID- 19182781
TI  - Phytoplankton in the ocean use non-phosphorus lipids in response to phosphorus
      scarcity.
AB  - Phosphorus is an obligate requirement for the growth of all organisms; major
      biochemical reservoirs of phosphorus in marine plankton include nucleic acids and
      phospholipids. However, eukaryotic phytoplankton and cyanobacteria (that is,
      'phytoplankton' collectively) have the ability to decrease their cellular
      phosphorus content when phosphorus in their environment is scarce. The
      biochemical mechanisms that allow phytoplankton to limit their phosphorus demand
      and still maintain growth are largely unknown. Here we show that phytoplankton,
      in regions of oligotrophic ocean where phosphate is scarce, reduce their cellular
      phosphorus requirements by substituting non-phosphorus membrane lipids for
      phospholipids. In the Sargasso Sea, where phosphate concentrations were less than
      10 nmol l-1, we found that only 1.3 +/- 0.6% of phosphate uptake was used for
      phospholipid synthesis; in contrast, in the South Pacific subtropical gyre, where
      phosphate was greater than 100 nmol l-1, plankton used 17 6% (ref. 6).
      Examination of the planktonic membrane lipids at these two locations showed that
      classes of sulphur- and nitrogen-containing membrane lipids, which are devoid of
      phosphorus, were more abundant in the Sargasso Sea than in the South Pacific.
      Furthermore, these non-phosphorus, 'substitute lipids' were dominant in
      phosphorus-limited cultures of all of the phytoplankton species we examined. In
      contrast, the marine heterotrophic bacteria we examined contained no substitute
      lipids and only phospholipids. Thus heterotrophic bacteria, which compete with
      phytoplankton for nutrients in oligotrophic regions like the Sargasso Sea, appear
      to have a biochemical phosphorus requirement that phytoplankton avoid by using
      substitute lipids. Our results suggest that phospholipid substitutions are
      fundamental biochemical mechanisms that allow phytoplankton to maintain growth in
      the face of phosphorus limitation.

PMID- 19182782
TI  - AcsD catalyzes enantioselective citrate desymmetrization in siderophore
      biosynthesis.
AB  - Bacterial pathogens need to scavenge iron from their host for growth and
      proliferation during infection. They have evolved several strategies to do this,
      one being the biosynthesis and excretion of small, high-affinity iron chelators
      known as siderophores. The biosynthesis of siderophores is an important area of
      study, not only for potential therapeutic intervention but also to illuminate new
      enzyme chemistries. Two general pathways for siderophore biosynthesis exist: the
      well-characterized nonribosomal peptide synthetase (NRPS)-dependent pathway and
      the NRPS-independent siderophore (NIS) pathway, which relies on a different
      family of sparsely investigated synthetases. Here we report structural and
      biochemical studies of AcsD from Pectobacterium (formerly Erwinia) chrysanthemi,
      an NIS synthetase involved in achromobactin biosynthesis. The structures of ATP
      and citrate complexes provide a mechanistic rationale for stereospecific
      formation of an enzyme-bound (3R)-citryladenylate, which reacts with L-serine to
      form a likely achromobactin precursor. AcsD is a unique acyladenylate-forming
      enzyme with a new fold and chemical catalysis strategy.

PMID- 19182783
TI  - Golgicide A reveals essential roles for GBF1 in Golgi assembly and function.
AB  - ADP ribosylation factor 1 (Arf1) plays a critical role in regulating secretory
      traffic and membrane transport within the Golgi of eukaryotic cells. Arf1 is
      activated by guanine nucleotide exchange factors (ArfGEFs), which confer spatial
      and temporal specificity to vesicular transport. We describe here the discovery
      and characterization of golgicide A, a potent, highly specific, reversible
      inhibitor of the cis-Golgi ArfGEF GBF1. Inhibition of GBF1 function resulted in
      rapid dissociation of COPI vesicle coat from Golgi membranes and subsequent
      disassembly of the Golgi and trans-Golgi network. Secretion of soluble and
      membrane-associated proteins was arrested at the endoplasmic reticulum-Golgi
      intermediate compartment, whereas endocytosis and recycling of transferrin were
      unaffected by GBF1 inhibition. Internalized shiga toxin was arrested within the
      endocytic compartment and was unable to reach the dispersed trans-Golgi network.
      Collectively, these results highlight the central role for GBF1 in coordinating
      bidirectional transport and maintaining structural integrity of the Golgi.

PMID- 19182784
TI  - Mechanistic and functional insights into fatty acid activation in Mycobacterium
      tuberculosis.
AB  - The recent discovery of fatty acyl-AMP ligases (FAALs) in Mycobacterium
      tuberculosis (Mtb) provided a new perspective of fatty acid activation. These
      proteins convert fatty acids to the corresponding adenylates, which are
      intermediates of acyl-CoA-synthesizing fatty acyl-CoA ligases (FACLs). Presently,
      it is not evident how obligate pathogens such as Mtb have evolved such new themes
      of functional versatility and whether the activation of fatty acids to
      acyladenylates could indeed be a general mechanism. Here, based on elucidation of
      the first structure of an FAAL protein and by generating loss-of-function and
      gain-of-function mutants that interconvert FAAL and FACL activities, we
      demonstrate that an insertion motif dictates formation of acyladenylate. Because
      FAALs in Mtb are crucial nodes in the biosynthetic network of virulent lipids,
      inhibitors directed against these proteins provide a unique multipronged approach
      to simultaneously disrupting several pathways.

PMID- 19182785
TI  - Dynamic modularity in protein interaction networks predicts breast cancer
      outcome.
AB  - Changes in the biochemical wiring of oncogenic cells drives phenotypic
      transformations that directly affect disease outcome. Here we examine the dynamic
      structure of the human protein interaction network (interactome) to determine
      whether changes in the organization of the interactome can be used to predict
      patient outcome. An analysis of hub proteins identified intermodular hub proteins
      that are co-expressed with their interacting partners in a tissue-restricted
      manner and intramodular hub proteins that are co-expressed with their interacting
      partners in all or most tissues. Substantial differences in biochemical structure
      were observed between the two types of hubs. Signaling domains were found more
      often in intermodular hub proteins, which were also more frequently associated
      with oncogenesis. Analysis of two breast cancer patient cohorts revealed that
      altered modularity of the human interactome may be useful as an indicator of
      breast cancer prognosis.

PMID- 19182786
TI  - Solution hybrid selection with ultra-long oligonucleotides for massively parallel
      targeted sequencing.
AB  - Targeting genomic loci by massively parallel sequencing requires new methods to
      enrich templates to be sequenced. We developed a capture method that uses
      biotinylated RNA 'baits' to fish targets out of a 'pond' of DNA fragments. The
      RNA is transcribed from PCR-amplified oligodeoxynucleotides originally
      synthesized on a microarray, generating sufficient bait for multiple captures at
      concentrations high enough to drive the hybridization. We tested this method with
      170-mer baits that target >15,000 coding exons (2.5 Mb) and four regions (1.7 Mb
      total) using Illumina sequencing as read-out. About 90% of uniquely aligning
      bases fell on or near bait sequence; up to 50% lay on exons proper. The
      uniformity was such that approximately 60% of target bases in the exonic 'catch',
      and approximately 80% in the regional catch, had at least half the mean coverage.
      One lane of Illumina sequence was sufficient to call high-confidence genotypes
      for 89% of the targeted exon space.

PMID- 19182787
TI  - Supramolecular control of the magnetic anisotropy in two-dimensional high-spin Fe
      arrays at a metal interface.
AB  - Magnetic atoms at surfaces are a rich model system for solid-state magnetic bits
      exhibiting either classical or quantum behaviour. Individual atoms, however, are
      difficult to arrange in regular patterns. Moreover, their magnetic properties are
      dominated by interaction with the substrate, which, as in the case of Kondo
      systems, often leads to a decrease or quench of their local magnetic moment.
      Here, we show that the supramolecular assembly of Fe and 1,4-benzenedicarboxylic
      acid molecules on a Cu surface results in ordered arrays of high-spin mononuclear
      Fe centres on a 1.5 nm square grid. Lateral coordination with the molecular
      ligands yields unsaturated yet stable coordination bonds, which enable chemical
      modification of the electronic and magnetic properties of the Fe atoms
      independently from the substrate. The easy magnetization direction of the Fe
      centres can be switched by oxygen adsorption, thus opening a way to control the
      magnetic anisotropy in supramolecular layers akin to that used in metallic thin
      films.

PMID- 19182788
TI  - Magnetic memory of a single-molecule quantum magnet wired to a gold surface.
AB  - In the field of molecular spintronics, the use of magnetic molecules for
      information technology is a main target and the observation of magnetic
      hysteresis on individual molecules organized on surfaces is a necessary step to
      develop molecular memory arrays. Although simple paramagnetic molecules can show
      surface-induced magnetic ordering and hysteresis when deposited on ferromagnetic
      surfaces, information storage at the molecular level requires molecules
      exhibiting an intrinsic remnant magnetization, like the so-called single-molecule
      magnets (SMMs). These have been intensively investigated for their rich quantum
      behaviour but no magnetic hysteresis has been so far reported for monolayers of
      SMMs on various non-magnetic substrates, most probably owing to the chemical
      instability of clusters on surfaces. Using X-ray absorption spectroscopy and X
      ray magnetic circular dichroism synchrotron-based techniques, pushed to the
      limits in sensitivity and operated at sub-kelvin temperatures, we have now found
      that robust, tailor-made Fe(4) complexes retain magnetic hysteresis at gold
      surfaces. Our results demonstrate that isolated SMMs can be used for storing
      information. The road is now open to address individual molecules wired to a
      conducting surface in their blocked magnetization state, thereby enabling
      investigation of the elementary interactions between electron transport and
      magnetism degrees of freedom at the molecular scale.

PMID- 19182789
TI  - The heterochromatin protein Swi6/HP1 activates replication origins at the
      pericentromeric region and silent mating-type locus.
AB  - Heterochromatin is a structurally compacted region of chromosomes in which
      transcription and recombination are inactivated. DNA replication is temporally
      regulated in heterochromatin, but the molecular mechanism for regulation has not
      been elucidated. Among heterochromatin loci in Schizosaccharomyces pombe, the
      pericentromeric region and the silent mating-type (mat) locus replicate in early
      S phase, whereas the sub-telomeric region does not, suggesting complex mechanisms
      for regulation of replication in heterochromatic regions. Here, we show that
      Swi6, an S. pombe counterpart of heterochromatin protein 1 (HP1), is required for
      early replication of the pericentromeric region and the mat locus. Origin-loading
      of Sld3, which depends on Dfp1/Dbf4-dependent kinase Cdc7 (DDK), is stimulated by
      Swi6. An HP1-binding motif within Dfp1 is required for interaction with Swi6 in
      vitro and for early replication of the pericentromeric region and mat locus.
      Tethering of Dfp1 to the pericentromeric region and mat locus in swi6-deficient
      cells restores early replication of these loci. Our results show that a
      heterochromatic protein positively regulates initiation of replication in
      silenced chromatin by interacting with an essential kinase.

PMID- 19182790
TI  - SOAR and the polybasic STIM1 domains gate and regulate Orai channels.
AB  - Influx of Ca(2+) through store-operated Ca(2+) channels (SOCs) is a central
      component of receptor-evoked Ca(2+) signals. Orai channels are SOCs that are
      gated by STIM1, a Ca(2+) sensor located in the ER but how it gates and regulates
      the Orai channels is unknown. Here, we report the molecular basis for gating of
      Orais by STIM1. All Orai channels are fully activated by the conserved STIM1
      amino acid fragment 344-442, which we termed SOAR (the STIM1 Orai activating
      region). SOAR acts in combination with STIM1 (450-485) to regulate the strength
      of interaction with Orai1. Activation of Orai1 by SOAR recapitulates all the
      kinetic properties of Orai1 activation by STIM1. However, mutations of STIM1
      within SOAR prevent activation of Orai1 but not co-clustering of STIM1 and Orai1
      in response to Ca(2+) store depletion, indicating that STIM1-Orai1 co-clustering
      is not sufficient for Orai1 activation. An intact carboxy terminus alpha-helicial
      region of Orai is required for activation by SOAR. Deleting most of the Orai1
      amino terminus impaired Orai1 activation by STIM1, but Orai1(Delta1-73)
      interacted with and was fully activated by SOAR. Accordingly, the characteristic
      inward rectification of Orai is mediated by an interaction between the polybasic
      STIM1 (672-685) and a Pro-rich region in the N terminus of Orai1. Hence, the
      essential properties of Orai1 function can be rationalized by interactions with
      discrete regions of STIM1.

PMID- 19182791
TI  - Chfr is linked to tumour metastasis through the downregulation of HDAC1.
AB  - Chfr is a ubiquitin ligase that functions in the mitotic checkpoint by delaying
      entry into metaphase in response to mitotic stress. It has been suggested that
      Chfr is a tumour suppressor as Chfr is frequently silenced in human cancers. To
      better understand how Chfr activity relates to cell-cycle progression and
      tumorigenesis, we sought to identify Chfr-interacting proteins using affinity
      purification combined with mass spectrometry. Histone deacetylase 1 (HDAC1),
      which represses transcription by deacetylating histones, was newly isolated as a
      Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its
      polyubiquitylation, both in vitro and in vivo. Ectopic expression of Chfr in
      cancer cells that normally do not express it results in downregulation of HDAC1,
      leading to upregulation of the Cdk inhibitor p21(CIP1/WAF1) and the metastasis
      suppressors KAI1 and E-cadherin. Coincident with these changes, cells arrest in
      the G1 phase of the cell cycle and become less invasive. Collectively, our data
      suggest that Chfr functions as a tumour suppressor by regulating HDAC1.

PMID- 19182792
TI  - An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting
      CEP63.
AB  - Activation of the protein kinases ATM and ATR following chromosomal breakage
      prevents initiation of DNA replication and entry into mitosis. However, the
      effects of ATM and ATR activation in cells already progressing through mitosis
      are poorly understood. Here we report that ATM and ATR activation induced by DNA
      double-strand breaks (DSBs) inhibits centrosome-driven spindle assembly in
      Xenopus laevis mitotic egg extract and somatic cells, delaying mitotic
      progression. Using a cDNA expression library to screen for ATM and ATR
      substrates, we identified centrosomal protein CEP63 as an ATM and ATR target
      required for normal spindle assembly. ATM and ATR phosphorylate Xenopus CEP63
      (XCEP63) on Ser 560 and promote its delocalization from the centrosome.
      Suppression of ATM and ATR activity or mutation of XCEP63 Ser 560 to Ala
      prevented spindle assembly defects. Consistently, inactivation of the CEP63 gene
      in avian DT40 cells impaired spindle assembly and prevented ATM- and ATR
      dependent effects on mitosis. These data indicate that ATM and ATR control
      mitotic events in vertebrate cells by targeting CEP63 and centrosome dependent
      spindle assembly.

PMID- 19182793
TI  - Programmed subcellular release for studying the dynamics of cell detachment.
AB  - Cell detachment is central to a broad range of physiopathological changes, but
      there are no quantitative methods to study this process. Here we report
      programmed subcellular release, a method for spatially and temporally controlled
      cellular detachment, and present quantitative results of the detachment dynamics
      of 3T3 fibroblasts at the subcellular level.

PMID- 19182794
TI  - The precision of remote context memories does not require the hippocampus.
AB  - Although the clarity of many memories fades with time, some memories may maintain
      their original precision. Here we used a context discrimination procedure to
      evaluate whether the hippocampus is important in maintaining precision as
      memories mature. Spared discrimination in hippocampal-lesioned mice indicated
      that precise, remote context memories may be supported by extra-hippocampal brain
      regions.

PMID- 19182795
TI  - Intra-retinal visual cycle required for rapid and complete cone dark adaptation.
AB  - Daytime vision is mediated by retinal cones, which, unlike rods, remain
      functional even in bright light and dark-adapt rapidly. These cone properties are
      enabled by rapid regeneration of their pigment. This in turn requires rapid
      chromophore recycling that may not be achieved by the canonical retinal pigment
      epithelium visual cycle. Recent biochemical studies have suggested the presence
      of a second, cone-specific visual cycle, although its physiological function
      remains to be established. We found that the Muller cells in the salamander
      neural retina promote cone-specific pigment regeneration and dark adaptation that
      are independent of the pigment epithelium. Without this pathway, dark adaptation
      of cones was slow and incomplete. Notably, the rates of cone pigment regeneration
      by the retina and pigment epithelium visual cycles were essentially identical,
      suggesting a possible common rate-limiting step. Finally, we also observed cone
      dark adaptation in the isolated mouse retina.

PMID- 19182796
TI  - Ephrin-B3 reverse signaling through Grb4 and cytoskeletal regulators mediates
      axon pruning.
AB  - It has been suggested that ephrin-B proteins have receptor-like roles in the
      control of axon pathfinding by repulsion, although it is largely unknown how the
      reverse signals are coupled to downstream intracellular molecules and how they
      induce cytoskeletal reorganization at the axon terminal. We found that ephrin-B3
      (EB3) was able to function as a repulsive guidance receptor and mediate
      stereotyped pruning of murine hippocampal mossy fiber axons during postnatal
      development. Targeted intracellular point mutants showed that axon pruning
      requires tyrosine phosphorylation-dependent reverse signaling and coupling to the
      SH2/SH3 adaptor protein Grb4 (also known as Nckbeta/Nck2). Furthermore, we found
      that the second SH3 domain of Grb4 is required and sufficient for axon
      pruning/retraction by mediating interactions with Dock180 and PAK to bring about
      guanine nucleotide exchange and signaling downstream of Rac, respectively. Our
      results reveal a previously unknown pathway that controls axon pruning and
      elucidate the biochemical mechanism by which ephrin-B reverse signals regulate
      actin dynamics to bring about the retraction of growth cones.

PMID- 19182797
TI  - NAMPT is essential for the G-CSF-induced myeloid differentiation via a NAD(+)
      sirtuin-1-dependent pathway.
AB  - We identified nicotinamide phosphoribosyltransferase (NAMPT), also known as pre-B
      cell colony enhancing factor (PBEF), as an essential enzyme mediating granulocyte
      colony-stimulating factor (G-CSF)-triggered granulopoiesis in healthy individuals
      and in individuals with severe congenital neutropenia. Intracellular NAMPT and
      NAD(+) amounts in myeloid cells, as well as plasma NAMPT and NAD(+) levels, were
      increased by G-CSF treatment of both healthy volunteers and individuals with
      congenital neutropenia. NAMPT administered both extracellularly and
      intracellularly induced granulocytic differentiation of CD34(+) hematopoietic
      progenitor cells and of the promyelocytic leukemia cell line HL-60. Treatment of
      healthy individuals with high doses of vitamin B3 (nicotinamide), a substrate of
      NAMPT, induced neutrophilic granulocyte differentiation. The molecular events
      triggered by NAMPT include NAD(+)-dependent sirtuin-1 activation, subsequent
      induction of CCAAT/enhancer binding protein-alpha and CCAAT/enhancer binding
      protein-beta, and, ultimately, upregulation of G-CSF synthesis and G-CSF receptor
      expression. G-CSF, in turn, further increases NAMPT levels. These results reveal
      a decisive role of the NAD(+) metabolic pathway in G-CSF-triggered myelopoiesis.

PMID- 19182798
TI  - A replication clock for Mycobacterium tuberculosis.
AB  - Few tools exist to assess replication of chronic pathogens during infection. This
      has been a considerable barrier to understanding latent tuberculosis, and efforts
      to develop new therapies generally assume that the bacteria are very slowly
      replicating or nonreplicating during latency. To monitor Mycobacterium
      tuberculosis replication within hosts, we exploit an unstable plasmid that is
      lost at a steady, quantifiable rate from dividing cells in the absence of
      antibiotic selection. By applying a mathematical model, we calculate bacterial
      growth and death rates during infection of mice. We show that during chronic
      infection, the cumulative bacterial burden-enumerating total live, dead and
      removed organisms encountered by the mouse lung-is substantially higher than
      estimates from colony-forming units. Our data show that M. tuberculosis
      replicates throughout the course of chronic infection of mice and is restrained
      by the host immune system. This approach may also shed light on the replication
      dynamics of other chronic pathogens.

PMID- 19182799
TI  - MIA40 is an oxidoreductase that catalyzes oxidative protein folding in
      mitochondria.
AB  - MIA40 has a key role in oxidative protein folding in the mitochondrial
      intermembrane space. We present the solution structure of human MIA40 and its
      mechanism as a catalyst of oxidative folding. MIA40 has a 66-residue folded
      domain made of an alpha-helical hairpin core stabilized by two structural
      disulfides and a rigid N-terminal lid, with a characteristic CPC motif that can
      donate its disulfide bond to substrates. The CPC active site is solvent
      accessible and sits adjacent to a hydrophobic cleft. Its second cysteine (Cys55)
      is essential in vivo and is crucial for mixed disulfide formation with the
      substrate. The hydrophobic cleft functions as a substrate binding domain, and
      mutations of this domain are lethal in vivo and abrogate binding in vitro. MIA40
      represents a thioredoxin-unrelated, minimal oxidoreductase, with a facile CPC
      redox active site that ensures its catalytic function in oxidative folding in
      mitochondria.

PMID- 19182800
TI  - Biological basis for restriction of microRNA targets to the 3' untranslated
      region in mammalian mRNAs.
AB  - MicroRNAs (miRNAs) interact with target sites located in the 3' untranslated
      regions (3' UTRs) of mRNAs to downregulate their expression when the appropriate
      miRNA is bound to target mRNA. To establish the functional importance of target
      site localization in the 3' UTR, we modified the stop codon to extend the coding
      region of the transgene reporter through the miRNA target sequence. As a result,
      the miRNAs lost their ability to inhibit translation but retained their ability
      to function as small interfering RNAs in mammalian cells in culture and in vivo.
      The addition of rare but not optimal codons upstream of the extended opening
      reading frame (ORF) made the miRNA target site more accessible and restored miRNA
      induced translational knockdown. Taken together, these results suggest that
      active translation impedes miRNA-programmed RISC association with target mRNAs
      and support a mechanistic explanation for the localization of most miRNA target
      sites in noncoding regions of mRNAs in mammals.

PMID- 19182801
TI  - Nucleosomes can invade DNA territories occupied by their neighbors.
AB  - Nucleosomes are the fundamental subunits of eukaryotic chromatin. They are not
      static entities, but can undergo a number of dynamic transitions, including
      spontaneous repositioning along DNA. As nucleosomes are spaced close together
      within genomes, it is likely that on occasion they approach each other and may
      even collide. Here we have used a dinucleosomal model system to show that the 147
      base-pair (bp) DNA territories of two nucleosomes can overlap extensively. In the
      situation of an overlap by 44 bp or 54 bp, one histone dimer is lost and the
      resulting complex can condense to form a compact single particle. We propose a
      pathway in which adjacent nucleosomes promote DNA unraveling as they approach
      each other and that this permits their 147-bp territories to overlap, and we
      suggest that these events may represent early steps in a pathway for nucleosome
      removal via collision.

PMID- 19182802
TI  - Helix movement is coupled to displacement of the second extracellular loop in
      rhodopsin activation.
AB  - The second extracellular loop (EL2) of rhodopsin forms a cap over the binding
      site of its photoreactive 11-cis retinylidene chromophore. A crucial question has
      been whether EL2 forms a reversible gate that opens upon activation or acts as a
      rigid barrier. Distance measurements using solid-state (13)C NMR spectroscopy
      between the retinal chromophore and the beta4 strand of EL2 show that the loop is
      displaced from the retinal binding site upon activation, and there is a
      rearrangement in the hydrogen-bonding networks connecting EL2 with the
      extracellular ends of transmembrane helices H4, H5 and H6. NMR measurements
      further reveal that structural changes in EL2 are coupled to the motion of helix
      H5 and breaking of the ionic lock that regulates activation. These results
      provide a comprehensive view of how retinal isomerization triggers helix motion
      and activation in this prototypical G protein-coupled receptor.

PMID- 19182803
TI  - Differential chromatin marking of introns and expressed exons by H3K36me3.
AB  - Variation in patterns of methylations of histone tails reflects and modulates
      chromatin structure and function. To provide a framework for the analysis of
      chromatin function in Caenorhabditis elegans, we generated a genome-wide map of
      histone H3 tail methylations. We find that C. elegans genes show distributions of
      histone modifications that are similar to those of other organisms, with H3K4me3
      near transcription start sites, H3K36me3 in the body of genes and H3K9me3
      enriched on silent genes. We also observe a novel pattern: exons are
      preferentially marked with H3K36me3 relative to introns. H3K36me3 exon marking is
      dependent on transcription and is found at lower levels in alternatively spliced
      exons, supporting a splicing-related marking mechanism. We further show that the
      difference in H3K36me3 marking between exons and introns is evolutionarily
      conserved in human and mouse. We propose that H3K36me3 exon marking in chromatin
      provides a dynamic link between transcription and splicing.

PMID- 19182804
TI  - Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia.
AB  - We report the discovery of a mutation in the THAP1 gene in three Amish-Mennonite
      families with mixed-onset primary torsion dystonia (also known as DYT6 dystonia).
      Another mutation in a German family with primary torsion dystonia suggests that
      THAP1 mutations also cause dystonia in other ancestry groups. We demonstrate that
      the missense mutation impairs DNA binding, suggesting that transcriptional
      dysregulation may contribute to the phenotype of DYT6 dystonia.

PMID- 19182805
TI  - Alpha-synuclein is part of a diverse and highly conserved interaction network
      that includes PARK9 and manganese toxicity.
AB  - Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy,
      collectively referred to as synucleinopathies, are associated with a diverse
      group of genetic and environmental susceptibilities. The best studied of these is
      PD. alpha-Synuclein (alpha-syn) has a key role in the pathogenesis of both
      familial and sporadic PD, but evidence linking it to other predisposition factors
      is limited. Here we report a strong genetic interaction between alpha-syn and the
      yeast ortholog of the PD-linked gene ATP13A2 (also known as PARK9). Dopaminergic
      neuron loss caused by alpha-syn overexpression in animal and neuronal PD models
      is rescued by coexpression of PARK9. Further, knockdown of the ATP13A2 ortholog
      in Caenorhabditis elegans enhances alpha-syn misfolding. These data provide a
      direct functional connection between alpha-syn and another PD susceptibility
      locus. Manganese exposure is an environmental risk factor linked to PD and PD
      like syndromes. We discovered that yeast PARK9 helps to protect cells from
      manganese toxicity, revealing a connection between PD genetics (alpha-syn and
      PARK9) and an environmental risk factor (PARK9 and manganese). Finally, we show
      that additional genes from our yeast screen, with diverse functions, are potent
      modifiers of alpha-syn-induced neuron loss in animals, establishing a diverse,
      highly conserved interaction network for alpha-syn.

PMID- 19182806
TI  - Variant in the sequence of the LINGO1 gene confers risk of essential tremor.
AB  - We identified a marker in LINGO1 showing genome-wide significant association (P =
      1.2 x 10(-9), odds ratio = 1.55) with essential tremor. LINGO1 has potent,
      negative regulatory influences on neuronal survival and is also important in
      regulating both central-nervous-system axon regeneration and oligodendrocyte
      maturation. Increased axon integrity observed in Lingo1 mouse [corrected]
      knockout models highlights the potential role of LINGO1 in the pathophysiology of
      ET [corrected]

PMID- 19182807
TI  - The peptidyl-prolyl isomerase Pin1 facilitates cytokine-induced survival of
      eosinophils by suppressing Bax activation.
AB  - The mechanisms by which cytokine signals prevent the activation and mitochondrial
      targeting of the proapoptotic protein Bax are unclear. Here we show, using
      primary human eosinophils, that in the absence of the prosurvival cytokines
      granulocyte-macrophage colony-stimulating factor and interleukin 5, Bax
      spontaneously underwent activation and initiated mitochondrial disruption.
      Inhibition of Bax resulted in less eosinophil apoptosis, even in the absence of
      cytokines. Granulocyte-macrophage colony-stimulating factor induced activation of
      the kinase Erk1/2, which phosphorylated Thr167 of Bax; this facilitated new
      interaction of Bax with the prolyl isomerase Pin1. Blockade of Pin1 led to
      cleavage and mitochondrial translocation of Bax and caspase activation,
      regardless of the presence of cytokines. Our findings indicate that Pin1 is a key
      mediator of prosurvival signaling and is a regulator of Bax function.

PMID- 19182808
TI  - The interleukin 23 receptor is essential for the terminal differentiation of
      interleukin 17-producing effector T helper cells in vivo.
AB  - Interleukin 23 (IL-23) is required for autoimmune inflammation mediated by IL-17
      producing helper T cells (T(H)-17 cells) and has been linked to many human immune
      disorders. Here we restricted deficiency in the IL-23 receptor to defined cell
      populations in vivo to investigate the requirement for IL-23 signaling in the
      development and function of T(H)-17 cells in autoimmunity, inflammation and
      infection. In the absence of IL-23, T(H)-17 development was stalled at the early
      activation stage. T(H)-17 cells failed to downregulate IL-2 and also failed to
      maintain IL-17 production or upregulate expression of the IL-7 receptor alpha
      chain. These defects were associated with less proliferation; consequently, fewer
      effector T(H)-17 cells were produced in the lymph nodes and hence available to
      emigrate to the bloodstream and tissues.

PMID- 19182810
TI  - The uncertain pathway to new therapeutics for SLE.

PMID- 19182809
TI  - Membrane protein architects: the role of the BAM complex in outer membrane
      protein assembly.
AB  - The folding of transmembrane proteins into the outer membrane presents formidable
      challenges to Gram-negative bacteria. These proteins must migrate from the
      cytoplasm, through the inner membrane and into the periplasm, before being
      recognized by the beta-barrel assembly machinery, which mediates efficient
      insertion of folded beta-barrels into the outer membrane. Recent discoveries of
      component structures and accessory interactions of this complex are yielding
      insights into how cells fold membrane proteins. Here, we discuss how these
      structures illuminate the mechanisms responsible for the biogenesis of outer
      membrane proteins.

PMID- 19182812
TI  - Do the benefits of alendronate for premenopausal women on high-dose
      glucocorticoids outweigh the risks?
AB  - Few data are available on the prevention of fracture in glucocorticoid-treated
      premenopausal women with autoimmune disorders such as systemic lupus
      erythematosus. In this setting, Okada et al. compared the effect of
      coadministration of alfacalcidol alone with that of alfacalcidol combined with
      alendronate. After 12 months of treatment, lumbar spine bone mineral density
      increased by 1.7% in the combination group, but decreased by 9.9% in the
      alfacalcidol-only group (P <0.001). Importantly, although no vertebral fractures
      were observed in the alendronate group, four patients in the alfacalcidol-only
      group experienced a vertebral fracture within 12-18 months of treatment. Although
      these data suggest that alendronate improves bone mineral density, we do not
      recommend the routine use of bisphosphonates in premenopausal women. Our reasons
      include the long-term skeletal retention of bisphosphonates, and the possible
      inhibitory effects on fetal skeletal maturation in pregnant patients. In
      addition, recent data suggest that premenopausal women who undergo glucocorticoid
      therapy have a low 10-year absolute risk of fracture.

PMID- 19182811
TI  - Are statins useful for treating vascular involvement in systemic sclerosis?
AB  - Research suggests that statins could be useful to treat vascular manifestations
      related to systemic sclerosis, but data on their potential clinical benefits
      remain limited. Previous studies suggested that statins increase the number of
      circulating endothelial precursor cells, and thereby improve the severity of
      Raynaud's phenomenon. Abou-Raya et al. have published the first randomized,
      double-blind, placebo-controlled clinical trial on the effect of statins on
      clinical outcomes in the vascular manifestations of systemic sclerosis. They
      observed significant reductions in the overall number of digital ulcers and in
      the mean number of new digital ulcers per patient in the statin group. In
      addition, statin-treated patients experienced significant improvements in
      disability scores and functional status. The data from this study indicate that
      statins might improve endothelial function, thereby contributing to clinical,
      functional recovery. These results pave the way for large studies on the use of
      statins in vascular complications related to systemic sclerosis.

PMID- 19182813
TI  - Imaging in osteoarthritis trials: useful or just expensive?

PMID- 19182814
TI  - New insights into the pathogenesis and genetics of psoriatic arthritis.
AB  - Psoriasis vulgaris and psoriatic arthritis (PsA) are inter-related heritable
      diseases. Psoriatic skin is characterized by hyperproliferative, poorly
      differentiated keratinocytes and severe inflammation. Psoriatic joints are
      characterized by highly inflamed synovia and entheses with focal erosions of
      cartilage and bone. Genetic analyses have uncovered risk factors shared by both
      psoriasis and PsA. Predisposition to psoriasis and PsA arising from common
      variation is most strongly conferred by the HLA class I region. Other genetic
      risk factors implicate the interleukin (IL)-23 pathway and the induction and
      regulation of type 17 T-helper cells in the pathogenesis of both diseases.
      Secretion of cytokines, such as IL-22 and IL-17, could result in the
      hyperproliferative phenotype of keratinocytes and potentially synoviocytes,
      leading to a vicious cycle of cellular proliferation and inflammation in both the
      skin and joints. In synovial tissue, disease-related cytokines could also promote
      osteoclast formation, resulting in bone erosion. The next step will be to
      identify genetic risk factors specifically associated with PsA. Although
      therapies that target tumor necrosis factor are often highly successful in the
      treatment of both diseases, genetic findings are likely to lead to the
      development of treatments tailored to an individual's genetic profile.

PMID- 19182815
TI  - Treating skeletal pain: limitations of conventional anti-inflammatory drugs, and
      anti-neurotrophic factor as a possible alternative.
AB  - Inflammatory and injury-induced skeletal pain are common conditions, and both
      conventional nonselective NSAIDs and the newer cyclo-oxygenase-2-specific
      inhibitors are widely used as post-traumatic and post-surgical analgesics.
      However, new research suggests that these drugs, particularly the cyclo-oxygenase
      2 inhibitors, have a negative effect on the healing process in fractured bone and
      within orthopedic surgical sites, thus highlighting a need to develop new
      approaches for managing skeletal pain. Various experimental studies have revealed
      that locally upregulated neurotrophic factors, especially nerve growth factor,
      have a major role in mediating injury-induced or inflammatory pain. Nerve growth
      factor inhibitors, therefore, might be an effective alternative modality for post
      traumatic and post-surgical analgesia, without impairing bone healing.

PMID- 19182816
TI  - The effect of melanism and vitamin D synthesis on the incidence of autoimmune
      disease.
AB  - Melanin has several physiological roles in maintaining health, but, notably, it
      affects the synthesis of vitamin D. Melanin is the primary determinant of the
      degree of skin pigmentation and protects the body from harmful ultraviolet
      radiation. Synthesis of 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) in the skin,
      however, is dependent on ultraviolet B light. Highly pigmented skin, to the level
      found in people of African origin, abrogates almost all ultraviolet-induced
      1,25(OH)(2)D(3) synthesis. Numerous animal models and clinical studies have
      underlined the essential role of vitamin D as a modulator of the different
      processes of the immune system. Evidence indicates that serum concentrations of
      1,25(OH)(2)D(3) and the prevalence of autoimmune diseases in a certain population
      are associated with the latitude at which that population resides. This article
      explores the relationship between skin pigmentation, vitamin D and the prevalence
      of autoimmune disease.

PMID- 19182818
TI  - Portfolio analysis and R&D decision making.

PMID- 19182817
TI  - Neurocognitive impairment in children and adolescents with systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, in which
      neuropsychiatric manifestations are a common cause of significant morbidity. The
      American College of Rheumatology has identified 19 distinct neuropsychiatric
      syndromes associated with SLE, although the 1982 American College of Rheumatology
      classification criteria for SLE recognize only two: seizures and psychosis.
      Neurocognitive impairment (NCI) is one of the most common and clinically
      challenging manifestations of SLE, but its pathophysiology remains poorly
      understood. This Review examines the epidemiology and pathophysiology of NCI in
      children and adolescents with SLE, as well as the diagnostic and therapeutic
      approaches that are available for these patients. As few published studies
      specifically address NCI in pediatric SLE, new directions for research are also
      discussed.

PMID- 19182819
TI  - The isolation and identification of apolipoprotein C-I in hormone-refractory
      prostate cancer using surface-enhanced laser desorption/ionization time-of-flight
      mass spectrometry.
AB  - Androgens play a central role in prostate cancer pathogenesis, and hence most of
      the patients respond to androgen deprivation therapies. However, patients tend to
      relapse with aggressive prostate cancer, which has been termed as hormone
      refractory. To identify the proteins that mediate progression to the hormone
      refractory state, we used protein-chip technology for mass profiling of patients'
      sera. This study included 16 patients with metastatic hormone-refractory prostate
      cancer who were initially treated with androgen deprivation therapy. Serum
      samples were collected from each patient at five time points: point A, pre
      treatment; point B, at the nadir of the prostate-specific antigen (PSA) level;
      point C, PSA failure; point D, the early hormone-refractory phase; and point E,
      the late hormone-refractory phase. Using surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry, we performed protein mass
      profiling of the patients' sera and identified a 6 640-Da peak that increased
      with disease progression. Target proteins were partially purified, and by amino
      acid sequencing the peak was identified as a fragment of apolipoprotein C-I (ApoC
      I). Serum ApoC-I protein levels increased with disease progression. On
      immunohistochemical analysis, the ApoC-I protein was found localized to the
      cytoplasm of the hormone-refractory cancer cells. In this study, we showed an
      increase in serum ApoC-I protein levels in prostate cancer patients during their
      progression to the hormone-refractory state, which suggests that ApoC-I protein
      is related to progression of prostate cancer. However, as the exact role of ApoC
      I in prostate cancer pathogenesis is unclear, further research is required.

PMID- 19182820
TI  - Prostate-specific antigen half-life: a new predictor of progression-free survival
      and overall survival in Chinese prostate cancer patients.
AB  - We investigated the potential value of prostate-specific antigen half-life
      (PSAHL) and decreasing velocity (PSAVd) to predict progression-free survival
      (PFS) and overall survival (OS) in Chinese patients with prostate cancer. A total
      of 153 patients treated with hormonal therapy were included in the study. Of
      these, 78 patients progressed to hormone-refractory prostate cancer (HRPC) and 24
      patients died by the end of follow-up. PSAHL was defined as the time during which
      prostate-specific antigen (PSA) concentration became half of the initial value
      during the first hormonal therapy. PSAVd reflected the decreasing velocity of PSA
      during the first hormonal therapy. PFS was defined as the interval from the
      beginning of hormonal therapy to HRPC. Cox proportional hazards regression
      analysis was used to evaluate whether PSAHL and PSAVd were significantly
      associated with PFS and OS. The median PSAHL and PSAVd were 0.50 months and 33.8
      ng mL(-1) per month. The median PFS and OS were 22.7 months (95% confidence
      interval [CI], 22.0-29.6 months) and 43.5 months (95% CI, 37.9-48.4 months),
      respectively. On univariate and multivariate analysis, long PSAHL (> 0.5 months),
      metastatic disease, high biopsy Gleason scores (>or= 8) and high nadir PSA (> 0.4
      ng mL(-1)) were all found to be significantly associated with short PFS. Long
      PSAHL, high nadir PSA and short PSA doubling time (PSADT <or= 2.0 months) were
      significantly associated with short OS. There were no significant relationships
      between PSAVd and either PFS or OS. Thus, PSAHL is a promising new independent
      predictor of survival. Patients with long PSAHL were identified as those at high
      risk for a relatively short PFS and OS.

PMID- 19182821
TI  - Human sperm quality and lipid content after migration into normal ovulatory human
      cervical mucus containing low numbers of leukocytes.
AB  - The aim of this study was to investigate whether a relationship exists between
      the presence of low numbers of leukocytes in normal ovulatory cervical mucus and
      sperm quality and lipid content after migration. The percentages of live, motile
      and morphologically normal spermatozoa, movement parameters assessed by computer
      aided sperm analysis (CASA), and ionophore-induced acrosome reaction measured by
      flow cytometry were determined before and after migration. High-performance
      liquid chromatography with ultraviolet detection was used to measure the sperm
      lipid content, including the various diacyl subspecies. The number of leukocytes
      found in solubilized mucus samples was counted using a haemocytometric method.
      Overall, the presence of leukocytes in the cervical mucus samples did not
      significantly influence sperm motility and morphology, sperm kinematic
      parameters, or the sperm content in sphingomyelin or cholesterol. In contrast,
      after migration, the decrease in various sperm diacyls and the level of induced
      acrosome reaction was significantly less pronounced in mucus samples
      containing>or=10(4) leukocytes than in mucus samples with no or rare leukocytes
      whereas the level of induced acrosome reaction was higher. The present data
      suggest that the low level of leukocytes found in normal ovulatory cervical mucus
      could influence the process of sperm lipid remodelling/capacitation.

PMID- 19182822
TI  - 2008: year of the rat for stem cell research.

PMID- 19182823
TI  - Epstein-Barr virus LMP2A accelerates MYC-induced lymphomagenesis.
AB  - Despite the identification of Epstein-Barr virus (EBV) in tumors of Burkitt's
      lymphoma (BL) over 40 years ago, the exact contribution of EBV to BL is
      undefined. EBV encodes for multiple proteins in latent B cells that affect B cell
      survival and activation. One such protein, latent membrane protein 2A (LMP2A),
      protects B cells from numerous pro-apoptotic stimuli. Therefore, we tested
      whether LMP2A protects B cells from apoptosis induced by aberrant c-MYC
      expression that precedes and dominates BL. We crossed LMP2A-transgenic mice
      (LMP2A-Tg), in which all B cells express LMP2A, to a transgenic mouse that
      expresses a BL translocation of myc (lambda-MYC-Tg mice). LMP2A promotes
      proliferation and protects B cells from MYC-induced apoptosis in lambda-MYC-Tg
      mice. LMP2A also accelerates the development of lymphoma in LMP2A/lambda-MYC-Tg
      mice. Finally, LMP2A increases the expression of Bcl-X(L) in both pre-tumor B
      cells and tumor cells, suggesting a mechanism for LMP2A-mediated B cell survival
      in the presence of MYC. These results support a hypothesis that EBV LMP2A
      promotes tumor development by protecting pre-tumor B cells that would normally
      apoptose after the c-myc translocation.

PMID- 19182824
TI  - Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer.
AB  - The BRCA1 and BRCA2 proteins are involved in the maintenance of genome stability
      and germ-line loss-of-function mutations in either BRCA1 or BRCA2 strongly
      predispose carriers to cancers of the breast and other organs. It has been
      demonstrated previously that inhibiting elements of the cellular DNA maintenance
      pathways represents a novel therapeutic approach to treating tumors in these
      individuals. Here, we show that inhibition of the telomere-associated protein,
      Tankyrase 1, is also selectively lethal with BRCA deficiency. We also demonstrate
      that the selectivity caused by inhibition of Tankyrase 1 is associated with an
      exacerbation of the centrosome amplification phenotype associated with BRCA
      deficiency. We propose that inhibition of Tankyrase 1 could be therapeutically
      exploited in BRCA-associated cancers.

PMID- 19182825
TI  - Convergence.

PMID- 19182826
TI  - Comment on "The future of agriculture".

PMID- 19182828
TI  - Not boring at all. Boron is the new carbon in the quest for novel drug
      candidates.

PMID- 19182829
TI  - When in Rome, reform. Radical reform of the Italian research and education
      systems is needed to address the lack of autonomy and lack of funding.

PMID- 19182830
TI  - Are there roles for observational database studies and structured quantification
      of expert opinion to answer therapy controversies in transplants?
AB  - Approaches to determine whether one transplant-related therapy is better than
      another include: (1) using experimental data, such as those from randomized
      controlled trials (RCTs); (2) using observational data, such as those from
      observational databases (ODBs) and (3) using conclusions from the structured
      quantification of expert opinion based on a consideration of evidence from RCTs,
      ODBs and other sources. Large RCTs are widely and appropriately regarded as the
      gold standard of clinical investigation. However, data from large RCTs are rarely
      available for transplant-related therapy questions. We discuss some of the
      limitations of RCTs in the transplant setting often including small size and
      short follow-up. These limitations are only partly solved by meta-analyses of
      RCTs. Data from high-quality ODBs are not only often useful in this setting but
      also have limitations. Biases may be difficult or impossible to identify and/or
      adjust for. However, ODBs have large numbers of diverse subjects receiving
      diverse therapies and analyses that often give answers more useful to clinicians
      than RCTs. Side-by-side comparisons suggest analyses from high-quality ODBs often
      give similar conclusions to meta-analyses of high-quality RCTs. Meta-analyses
      combining data from RCTs and ODBs are sometimes appropriate. Quantitation of
      expert opinion, when of high quality, is also useful: experts rarely disagree
      under precisely defined circumstances and their consensus conclusions are often
      concordant with results of high-quality RCTs and ODBs. We suggest increased use
      of ODBs and expert opinion as reliable and effective ways to determine relative
      efficacies of new therapies in transplant settings.

PMID- 19182831
TI  - Rescue from failed growth factor and/or chemotherapy HSC mobilization with G-CSF
      and plerixafor (AMD3100): an institutional experience.
AB  - Auto-SCT has been shown to be a potentially curative treatment for a variety of
      hematological malignancies. Auto-SCT is dependent on the successful mobilization
      and collection of hematopoietic stem cells to ensure engraftment. The inability
      to mobilize sufficient number of hematopoietic stem cells using standard cytokine
      assisted mobilization strategies excludes eligible patients from potentially
      curative auto-SCT. Plerixafor (AMD3100; Mozobil), a novel bicyclam antagonist of
      the SDF-1alpha/CXCR4 complex, has been reported previously to augment PBSC
      mobilization in patients undergoing their first planned stem cell mobilization
      and collection attempt. In our experience, 17 of 20 patients otherwise eligible
      for auto-SCT who failed previous mobilization attempts had successful
      mobilization of CD34(+) hematopoietic stem cells with one apheresis procedure,
      and an additional patient required two aphereses procedures, when treated with
      the combination of plerixafor and G-CSF on a compassionate use protocol available
      at our institution.

PMID- 19182832
TI  - Age-dependent pharmacokinetic profile of single daily dose i.v. busulfan in
      children undergoing reduced-intensity conditioning stem cell transplant.
AB  - We studied the pharmacokinetic (PK) profile of single daily dose i.v. BU in
      children who underwent reduced-intensity conditioning (RIC) transplantation. A
      cohort of 19 patients < or =4 years of age (group 1) and 33 patients >4 years
      (group 2) was studied. Patients received a BU test dose for PK studies, followed
      by two treatment doses adjusted to target an area under the curve (AUC) of 4000
      microM min per day. Patients in group 1 attained a lower AUC as compared to group
      2 (3568 vs 4035 microM min). In group 1, 67% patients and in group 2, 84%
      patients achieved AUC within the targeted range. Stable donor chimerism was
      achieved in 56% patients in group 1 and 79% in group 2. Eight patients required a
      second transplantation because of graft failure. Because of the concern that a
      low AUC adversely affected outcomes, a second cohort of 23 patients followed a
      modified protocol with a targeted AUC of 5000 microM min. A higher AUC was
      attained (4825 microM min). Stable donor chimerism was achieved in 91% of
      patients. Our results show that RIC regimens using two single daily doses of i.v.
      BU are effective in children, but a targeted AUC of 5000 microM min is
      recommended.

PMID- 19182833
TI  - Short and long-term safety of lenograstim administration in healthy peripheral
      haematopoietic progenitor cell donors: a single centre experience.
AB  - Healthy donors (HDs) who were mobilized using lenograstim (LENO) and who were
      undergoing peripheral haematopoietic progenitor cell collection with apheresis
      (HPC-A) were enrolled in a surveillance protocol. In all, 184 HDs have been
      assessed with a median follow-up of 62 months (range 2-155). HDs received LENO at
      a median dose of 10 microg/kg (range 5-15). Bone pain was reported as the most
      frequent short-term adverse event (71.2%). Other commonly observed short-term
      symptoms included fatigue (19.0%), fever (5.4%), headache (27.7%), nausea (12.0%)
      and insomnia (22.3%). Spleen size increased in 4.3% of the donors. No vascular
      disorders or cardiac disease occurred. Long-term follow-up included monitoring of
      adverse events, neoplastic disease or other pathologies. Transit ischaemic attack
      occurred in one donor (39 months post-donation). One autoimmune event was
      reported at 28 months post-recombinant human granulocyte (rhG)-CSF (ankylosing
      spondylitis); one donor with a history of chronic obstructive pulmonary disease
      developed secondary polyglobulia (50 months post-rhG-CSF). One donor was
      diagnosed with lung cancer at 19 months post-donation. No haematological disease
      was observed. In conclusion, the short-term safety appears to be verified,
      whereas, although the study identified no increased risks of malignancy among HDs
      who received rhG-CSF, long-term safety requires more complete data sets,
      especially a longer follow-up and a larger number of HDs.

PMID- 19182834
TI  - Filgrastim support in allogeneic HSCT for myeloid malignancies: a review of the
      role of G-CSF and the implications for current practice.
AB  - The cytokine G-CSF stimulates myeloid progenitors and is routinely used to
      accelerate neutrophil recovery in the treatment of hematological malignancy and
      blood or marrow transplantation. Despite significant reductions in the frequency
      and duration of febrile neutropenia episodes, infections and the length of
      hospitalization, filgrastim has never been conclusively proven to produce a
      survival benefit in allogeneic HSCT and is considered a supportive measure. In
      this review, we analyze the conflicting evidence and appraise the utility of G
      CSF in allogeneic HSCT. G-CSF administration after allogeneic HSCT needs to take
      into consideration the impact on immune reconstitution, risk of leukemic
      progression in patients with chromosome 7 abnormalities and the absence of proven
      benefit in patients receiving marrow or peripheral blood progenitors as the stem
      cell source.

PMID- 19182835
TI  - DMSO-associated encephalopathy during autologous peripheral stem cell infusion: a
      predisposing role of preconditioning exposure to CNS-penetrating agents?

PMID- 19182836
TI  - Insights into future directions for diabetes management and prevention.

PMID- 19182837
TI  - Return of the great pretender: ectopic pregnancy.

PMID- 19182838
TI  - Hospital admissions for people with diagnosed diabetes: challenges for diabetes
      prevention and management programmes.
AB  - AIM: To identify the extent to which people with diabetes are admitted as
      inpatients to Counties Manukau District Health Board (CMDHB) hospitals compared
      to all New Zealand, and the costs of these admissions. METHOD: Search of National
      Minimum Dataset for inpatient public hospital discharges with any mention of Type
      1 or Type 2 diabetes from 1996-2007. RESULTS: Overall 13% of all CMDHB inpatient
      discharges mentioned diabetes in 2007 compared with 12% nationally. There were
      differences by ethnicity among those discharges aged 45 to 64 years, with Pacific
      (38%), Indian (31%) and Maori (31%) being more than three times as likely as
      European/Other people (10%) to experience a diabetes-recorded admission. There
      was a substantial increase in the rate of admission per 1000 where diabetes was
      recorded over 1996-2007, with Maori (31%) and Pacific (52%) people aged 45-64
      years showing the largest increases. Findings from Counties Manukau tended to be
      comparable with total New Zealand data in terms of the percentage of people with
      diabetes who were inpatients in 2007, but relatively more inpatients in Counties
      Manukau had diabetes recorded (consistent with its high population of people with
      diabetes). Costs of admissions, laboratory investigations, and pharmaceuticals
      for people with diabetes were estimated to be $66 million per annum higher than
      for people without diabetes, in Counties Manukau alone. CONCLUSION: The findings
      give support to balanced system-wide strategies (such as the Let's Beat Diabetes
      programme in Counties Manukau) that focus on both upstream (prevention) and
      downstream (management and coordinated care) responses to diabetes. The study
      points to a long-term and significant capacity challenge for secondary care
      services to respond to the forecast growth in the incidence of Type 2 diabetes,
      particularly in Counties Manukau. The findings also pose challenges for transfer
      of care to primary care providers after a hospital episode and the flow of
      information between care settings.

PMID- 19182839
TI  - Hospital expenditure on treating complications of diabetes and the potential for
      deferring complications in Canterbury, New Zealand.
AB  - AIM: To investigate annual expenditure by a major district health board in New
      Zealand on hospital admissions for treating the various complications of
      diabetes. METHODS: Actual costs were analysed for 2005/06, for all inpatient
      hospital admissions in Canterbury, New Zealand, where diabetes was recorded as a
      primary or secondary diagnosis. Costs and lengths of stay for all such admissions
      were included for ICD-10 codes using the criteria from Australian studies of
      potentially avoidable hospitalisations. ICD-10 codes were used to identify the
      major types of complications of diabetes resulting in hospital admissions.
      RESULTS: Total costs of all hospital admissions where diabetes was recorded as a
      primary or secondary diagnosis amounted to $10.1 million in 2005/06, and 9511
      days stay in hospital; 69% of these costs were for admissions where diabetes was
      a secondary diagnosis, with the majority of such costs being for treatment of
      admissions for cardiovascular disease. CONCLUSIONS: The results generally
      indicated that diabetes associated with hospital admissions is a major factor,
      which is still under-reported, and which involves considerable costs of treating
      the longer term consequences of diabetes. The largest proportion of these costs
      is for cardiovascular disease, where diabetes is the secondary diagnosis.

PMID- 19182840
TI  - Prevalence of undiagnosed diabetes, impaired glucose tolerance, and impaired
      fasting glucose among Maori in Te Wai o Rona: Diabetes Prevention Strategy.
AB  - AIMS: To describe the prevalence of undiagnosed diabetes, impaired glucose
      tolerance (IGT) and impaired fasting glucose (IFG) ("dysglycaemia") among Maori.
      METHODS: Te Wai o Rona: Diabetes Prevention Strategy was a trial of lifestyle
      change among Maori families in the Waikato/Lakes areas of New Zealand. All Maori
      family household members aged > or = 28 years, without known diabetes, were
      invited to participate through primary care, community, and media approaches.
      Participants were invited to have an oral glucose tolerance test (OGTT). RESULTS:
      Of the 3817 eligible Maori, mean BMI was 32.9+/-7.8 kg/m2 (women) and 33.1+/-6.7
      kg/m2 (men). The age standardised prevalence of undiagnosed diabetes was higher
      among men than women (6.5[5.8-7.4]% vs 4.2[3.6-4.8]%), as was that for IFG
      (5.4[4.7-6.1]% vs 3.0[2.3-3.5]%), but not IGT (8.5[7.6-9.4]% vs 9.7[8.7-10.6]%)
      with no rural-urban differences. The prevalence of dysglycaemia increased with
      increasing BMI with no clear inflection point and was 1.33(1.11-1.60) greater
      among those with a community services card after adjusting for age, sex and BMI.
      CONCLUSIONS: Undiagnosed diabetes, IGT, and IFG remain common among Maori,
      particularly men, the very obese, and those with greater socioeconomic
      disadvantage. There remains significant opportunity to reduce Maori morbidity and
      premature mortality through diabetes case-finding and intervention.

PMID- 19182841
TI  - The outcomes of transrectal ultrasound guided biopsy of the prostate in a New
      Zealand population.
AB  - INTRODUCTION: We aim to produce nomograms relating age, digital rectal
      examinations (DRE), and prostate specific antigen (PSA) to probability of a
      positive transrectal ultrasound guided (TRUS) prostate biopsy for a New Zealand
      population. Usefulness of age-adjusted PSA reference ranges and PSA density are
      also examined. METHODS: Data was extracted retrospectively from electronic
      records of prostate biopsies performed between 1995-2007 in Christchurch, New
      Zealand. Nomograms were created using logistic regression models. The area under
      the curve (AUC) for age-adjusted PSA ranges, PSA density, and PSA in predicting a
      positive biopsy was calculated and used to compare these methods. RESULTS: 4316
      biopsies were available for analysis. Data was incomplete for 1177 (27%) of
      patients. Biopsy was positive in 54.4%. PSA level and DRE finding were strong
      predictors of a malignant biopsy in our multivariable model but age was not. PSA
      level and DRE were also predictors of a higher Gleason score (7 or greater).
      Nomograms are presented relating PSA and DRE to both a positive biopsy result and
      to biopsy with Gleason score 7 or greater. AUC for age adjusted reference ranges
      was no better than PSA using a single cutpoint of 4.0. (0.54 vs 0.53). AUC for
      PSA density using a cutpoint of 0.15 was 0.72. Receiver Operator Characteristic
      (ROC) curves showed a clear advantage for PSA density over PSA regardless of
      cutpoint. (AUC 0.80 vs 0.67). CONCLUSIONS: Nomograms are formulated to help
      inform New Zealand men how likely they are to have a positive TRUS prostate
      biopsy and also how likely they are to have a higher grade cancer detected by
      TRUS prostate biopsy. Age-adjusted reference ranges did not improve prediction of
      cancer in this population, but the use of PSA density may enhance prostate cancer
      diagnosis.

PMID- 19182842
TI  - Accuracy of prenatal diagnosis in a tertiary fetal medicine unit.
AB  - AIMS: To establish the accuracy of prenatal diagnosis in a tertiary referral
      fetal medicine unit by comparing those diagnoses made prenatally with diagnoses
      made at birth until discharge, and with postmortem information from cases that
      resulted in termination, intrauterine, or neonatal death. METHODS: All cases seen
      in the Fetal Medicine Unit between 1 June 2004 and 30 November 2005 were
      collected prospectively and sorted according to diagnosis. Relevant outcome data
      for these pregnancies were collected including postmortem information. RESULTS:
      681 cases seen which accounted for 1219 visits. 198 were classified prenatally as
      a major abnormality, 46 cases minor, 56 with raised nuchal translucency, and 381
      no abnormality. Outcome details were not available for analysis in two cases.
      Therefore 679 (99.7%) cases were available (711 out of 713 fetuses). Of the
      liveborns, 93.6% of the prenatal diagnoses were confirmed, 5.1% were resolved
      (predominantly soft markers), and 1.3% resulted in an additional major
      abnormality that had a significant clinical effect. Postmortem examinations were
      performed on 52% fetal or neonatal deaths with a normal or unknown karyotype.
      There was one new finding at postmortem that changed the fetal medicine diagnosis
      significantly. CONCLUSIONS: Accuracy of prenatal diagnosis in a tertiary fetal
      medicine unit is high. Parents and staff need to be aware that not all
      abnormalities will be detected prenatally, but inaccurate diagnosis is uncommon.
      Clinical indicators for benchmarking need to be developed.

PMID- 19182843
TI  - Obstructing the goal? Hospitalisation for netball injury in New Zealand 2000
      2005.
AB  - AIM: The last descriptive epidemiological study of netball injuries in New
      Zealand was published in 1993 (data from 1988). The current study examines the
      changes in the injury profile of hospitalised netball cases since then. METHOD:
      Records of public hospital inpatients discharged in the period 2000-2005 were
      searched for netball injury cases using a novel search procedure. Data were
      analysed by demographics, body region, nature/severity of injury, and medical
      procedure. RESULTS: 1126 cases were identified; 81% were female. The average age
      was 29 years (5-82 years); 26% of cases were Maori. The highest incidence rate
      was 325 per 100,000 participants 35-49 years. The population injury rate was 5.0
      per 100,000. Forearm fractures predominated in the 0-14 year age-group and
      Achilles tendon injury in the 15+ age-groups. Six cases (0.5%) sustained a
      "serious" injury (ICISS score < or = 0.941), >50% of cases had an injury that
      would require a "lay-off" period of 3-6 months. CONCLUSION: The differences
      highlighted in this study, between hospitalised netball injury in the late 1980s
      and the present, suggest that (a) the average age of hospitalised netball injury
      cases may be increasing, (b) forearm fractures in young netball players are a
      cause for concern, (c) surgical repair of Achilles tendon injuries appears to
      have increased while knee ligament injuries requiring hospitalisation/surgical
      repair appear to have decreased, and (d) the indoor version of the game and male
      players may be important targets for injury prevention.

PMID- 19182844
TI  - (Non)regulation of marketing of unhealthy food to children in New Zealand.
AB  - Three and a half years ago an editorial in the NZMJ called for restrictions on
      marketing of unhealthy food to New Zealand children. This paper discusses
      progress since then. There has been a seemingly relentless documentation of
      adverse health consequences of the obesity epidemic in the intervening years,
      increasing evidence that marketing of unhealthy food contributes to the epidemic,
      growing knowledge about New Zealand children's exposure to marketing of unhealthy
      food, and evidence of public support to decrease children's exposure to marketing
      of unhealthy food. Yet there is still a lack of substantive action on the
      restriction of marketing of unhealthy food to children in New Zealand.

PMID- 19182845
TI  - Heart health in New Zealand.
AB  - Global health is increasingly dominated by chronic diseases--cardiovascular
      diseases, cancer, chronic respiratory diseases and diabetes. New Zealand
      cardiovascular disease death rates have fallen by over 60% since their peak in
      the late 1960s. Most of the decline can be explained by favourable trends in the
      main risk factors. Despite these gains, there will be an increasing burden in
      elderly, Maori, and economically disadvantaged people. There are two major
      challenges. Firstly, to implement a balanced public health approach to the
      prevention and control of vascular disease and to ensure a reduction in overall
      population levels of risk and a reduction in risk levels of high-risk people.
      Secondly, to promote health equity in New Zealand, initially by encouraging a
      rapid reduction in tobacco use in Maori and Pacific Island people.

PMID- 19182846
TI  - Ruptured tubal ectopic pregnancy with negative serum beta hCG--a case for ongoing
      vigilance?
AB  - A 25-year-old female with a history of recent miscarriage presents with
      haemodynamic shock and a negative serum beta hCG. She presents to six different
      healthcare facilities within a single metropolitan area, during which a pelvic
      ultrasound scan showed an empty uterus with a subnormal rise in serum beta hCG.
      Suspected ruptured tubal ectopic pregnancy was confirmed following laparoscopy
      and salpingectomy, with histopathological confirmation of chorionic villi in the
      extirpated fallopian tube. This case report highlights the ongoing clinical
      diagnostic challenges that are associated with ectopic pregnancy; illustrates the
      importance of teamwork; and perhaps also draws attention to the need for a robust
      protocol to facilitate consistent, good-quality early pregnancy care for all
      women.

PMID- 19182847
TI  - Carbamazepine and falsely positive screening tests for Cushing's syndrome.
AB  - A case of markedly elevated 24-hour urine-free cortisol levels, mainly due to
      interference with carbamazepine when measuring with high performance liquid
      chromatography but also due to increased fluid intake, is presented. Moreover,
      the 1 mg overnight dexamethasone suppression test was positive and the midnight
      serum cortisol level was slightly increased, probably as a result of
      carbamazepine-induced activity of CYP3A4 and increased levels of cortisol binding
      globulin.

PMID- 19182848
TI  - Medical image. A colloid cyst in the third ventricle.

PMID- 19182849
TI  - Medical image. Unilateral diaphragmatic paralysis.

PMID- 19182850
TI  - Health and safety will be the death of us.

PMID- 19182851
TI  - Discussing end-of-life issues with Asian patients and their families.

PMID- 19182852
TI  - National Immunisation Register inaccuracies and duplications.

PMID- 19182853
TI  - Research into the Cartwright Inquiry.

PMID- 19182854
TI  - Identification of nonregulated pollutants in North Sea-produced water discharges.
AB  - Produced water collected from oil and gas platforms on the United Kingdom
      Continental Shelf was characterized for nonregulated pollutants through an
      effects-directed analysis procedure. Produced water samples were characterized
      for the presence of aryl hydrocarbon receptor (AhR) and estrogen receptor (ER)
      agonists using the dioxin-responsive, chemical-activated luciferase gene
      expression assay (DR-CALUX) and yeast estrogen screen (YES) bioassays. The AhR
      and ER agonists were then isolated by normal-phase, high-performance liquid
      chromatography and identified using gas chromatography coupled to mass
      spectrometry in a number of formats. The identified compounds were cross
      referenced with those compounds routinely analyzed and regarded by the Oslo and
      Paris (OSPAR) Commission for the North East Atlantic as priority hazardous
      substances. The occurrence in produced water of a number of nonregulated
      compounds with demonstrable potential environmental effects is presented, to our
      knowledge for the first time. These include persistent organic contaminants, such
      as hexachlorobenzene, decachlorobiphenyl, and octachlorodibenzofuran.

PMID- 19182857
TI  - The rural allied health workforce study (RAHWS): background, rationale and
      questionnaire development.
AB  - The allied health professions form approximately 18% of the health workforce in
      Australia and are well placed to contribute to future multidisciplinary models of
      health care. There are many reports describing the health workforce in Australia
      for the medical and nursing professions but there is very little information
      available about the nature of the allied health workforce. Recent studies have
      highlighted the need for more current and detailed information about the rural
      allied health workforce to inform future workforce planning. National health
      policy reform requires that new healthcare models take into account future
      workforce requirements, the distribution and work contexts of existing
      practitioners, training needs, workforce roles and scope of practice. The absence
      of accurate data profiling the existing rural allied health workforce makes this
      impossible. The Rural Allied Health Workforce Study (RAHWS) aims to use a cross
      sectional survey instrument with high validity to provide a large scale but
      detailed profile of the allied health workforce in regional, rural and remote
      Australia. The RAHWS survey instrument used in this study is the result of a
      comprehensive consultation with clinicians, academics and managers. The RAHWS
      survey instrument has been designed to provide uniform data across a wide range
      of healthcare settings. Good concurrent and face validity have been demonstrated
      and its design allows for data analysis using a wide range of variables. Cross
      correlation of responses can answer a number of research questions in relation to
      rural recruitment and retention, professional education and service delivery
      models. This valid and feasible instrument will be used to explore the rural
      allied health workforce by implementing the RAHWS survey in rural regions on a
      state-by-state basis in Australia during 2009 and 2010.

PMID- 19182858
TI  - Vietnamese-born health professionals: negotiating work and life in rural
      Australia.
AB  - INTRODUCTION: Australia is a culturally diverse nation due to migrants from a
      wide variety of countries creating a multicultural society. The health
      professions are highly valued by the younger generation of overseas-born migrants
      who have acculturated into Australian society; many have chosen health care as
      their profession in Australia. However, most migrants settle in metropolitan
      areas and young health professionals may find working in rural or remote
      Australia culturally and professionally highly challenging. The present study of
      migrant health professionals examined the life experiences and acculturation
      strategies of Vietnamese-born health professionals working and living in rural
      Australia. OBJECTIVES: The two main study objectives were to: (1) examine aspects
      of the acculturation of overseas-born and Australian-trained health professionals
      in the Australian health discourse; and (2) identify key coping strategies used
      by them when in working in the rural context. METHODS: Six overseas-born,
      Australian-trained health professionals were invited to participate in this
      qualitative study using a snowball sampling technique. The participants were all
      born in Vietnam and had experienced working in rural Australia. They included
      three medical doctors, a dentist, a physiotherapist and a nurse. The interviews
      were recorded and four participants also provided additional written responses to
      some of the open-ended interview questions. The interview data were transcribed
      and later coded for thematic analysis. Topics and themes that emerged focused on
      the issues and strategies of acculturation to the rural health context. RESULTS:
      The study showed that the acculturation process was affected by the participants'
      views about and attitudes towards working in an Australian rural context. The
      study identified these essential strategies used by the participants in adapting
      to a new workplace: collaborating, distancing, adjusting, repairing, and
      accommodating. CONCLUSION: The study provides insights into the lives of these
      health professionals in a rural context, and particularly their experience of
      cultural shock and the coping strategies they may use. A need is identified for a
      larger study to inform recruitment and retention of these health professionals to
      rural Australia, and to assist universities to prepare such students and their
      clinical supervisors for rural placements.

PMID- 19182860
TI  - Novel inhibitors of human histone deacetylase (HDAC) identified by QSAR modeling
      of known inhibitors, virtual screening, and experimental validation.
AB  - Inhibitors of histone deacetylases (HDACIs) have emerged as a new class of drugs
      for the treatment of human cancers and other diseases because of their effects on
      cell growth, differentiation, and apoptosis. In this study we have developed
      several quantitative structure-activity relationship (QSAR) models for 59
      chemically diverse histone deacetylase class 1 (HDAC1) inhibitors. The variable
      selection k nearest neighbor (kNN) and support vector machines (SVM) QSAR
      modeling approaches using both MolconnZ and MOE chemical descriptors generated
      from two-dimensional rendering of compounds as chemical graphs have been
      employed. We have relied on a rigorous model development workflow including the
      division of the data set into training, test, and external sets and extensive
      internal and external validation. Highly predictive QSAR models were generated
      with leave-one-out cross-validated (LOO-CV) q2 and external R2 values as high as
      0.80 and 0.87, respectively, using the kNN/MolconnZ approach and 0.93 and 0.87,
      respectively, using the SVM/MolconnZ approach. All validated QSAR models were
      employed concurrently for virtual screening (VS) of an in-house compound
      collection including 9.5 million molecules compiled from the ZINC7.0 database,
      the World Drug Index (WDI) database, the ASINEX Synergy libraries, and other
      commercial databases. VS resulted in 45 structurally unique consensus hits that
      were considered novel putative HDAC1 inhibitors. These computational hits had
      several novel structural features that were not present in the original data set.
      Four computational hits with novel scaffolds were tested experimentally, and
      three of them were confirmed active against HDAC1, with IC50 values for the most
      active compound of 1.00 microM. The fourth compound was later identified to be a
      selective inhibitor of HDAC6, a Class II HDAC. Moreover, two of the confirmed
      hits are marketed drugs, which could potentially facilitate their further
      development as anticancer agents. This study illustrates the power of the
      combined QSAR-VS method as a general approach for the effective identification of
      structurally novel bioactive compounds.

PMID- 19182866
TI  - DNA double helix unwinding triggers transcription block-dependent apoptosis: a
      semiquantitative probe of the response of ATM, RNAPII, and p53 to two DNA
      intercalators.
AB  - We have previously shown the binding modes of two DNA interacting analogues (1)a
      {3-(4-methyl-piperazin)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile} and
      (3)a {3-(3-dimethylamino-propylamino)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9
      carbonitrile} with the DNA double helix. In this study, we have determined the
      notably different DNA damage signal pathway elicited by (1)a and (3)a due to the
      different extents to which they unwind the DNA double helix. First, we have
      identified that ataxia-telangiectasia-mutated (ATM) protein kinase can respond to
      DNA double helix unwinding caused by both (1)a and (3)a. In addition, the amount
      of ATM activation is consistent with the degree to which the DNA double helix was
      unwound. Consequently, we used (1)a and (3)a to semiquantitatively probe the
      response of RNA polymerase II (RNAPII) and p53 toward DNA double helix unwinding
      in vivo. By means of flow cytometry, immunocytochemistry, ChIP, quantitative real
      time polymerase chain reaction, and Western blot analyses, we measured the level
      of p53 and RNAPII phosphorylation, in addition to the dynamics of the RNAPII
      distribution along the c-Myc gene. These results provided novel evidence for the
      impact of subtle DNA structural changes on the activity of RNAPII and p53.
      Moreover, DNA double helix conformational damage-dependent apoptosis was studied
      for the first time. These results indicated that (1)a can induce transcriptional
      blockage following a shift of the unphosphorylated IIa form of RNAPII to the
      phosphorylated IIo form, while (3)a is unable to induce the same effect.
      Subsequently, p53 accumulation and phosphorylation events occur that lead to
      apoptosis in the case of (1)a exposure. This suggests that the transcriptional
      blockage is also correlated to the degree of double helix unwinding. Furthermore,
      we found that the degree of DNA conformational damage determines whether or not
      apoptosis occurs through transcriptional blockage. Under our experimental
      conditions, ATM does not participate in the downstream events even when it has
      been activated. Thus, p53-mediated apoptosis may be independently triggered by
      transcriptional blockage.

PMID- 19182865
TI  - The Gbeta5-RGS7 complex selectively inhibits muscarinic M3 receptor signaling via
      the interaction between the third intracellular loop of the receptor and the DEP
      domain of RGS7.
AB  - Regulators of G protein signaling (RGS) make up a diverse family primarily known
      as GTPase-activating proteins (GAPs) for heterotrimeric G proteins. In addition
      to the RGS domain, which is responsible for GAP activity, most RGS proteins
      contain other distinct structural motifs. For example, members of the R7 family
      of RGS proteins contain a DEP, GGL, and novel DHEX domain and are obligatory
      dimers with G protein beta subunit Gbeta5. Here we show that the Gbeta5-RGS7
      complex can inhibit Ca2+ mobilization elicited by muscarinic acetylcholine
      receptor type 3 (M3R), but not by other Gq-coupled receptors such as M1, M5,
      histamine H1, and GNRH receptors. The isolated DEP domain of RGS7 is sufficient
      for the inhibition of M3R signaling, whereas the deletion of the DEP domain
      renders the Gbeta5-RGS7 complex ineffective. Deletion of a portion of the third
      intracellular loop allowed the receptor (M3R-short) to signal but rendered it
      insensitive to the effect of the Gbeta5-RGS7 complex. Accordingly, the
      recombinant DEP domain bound in vitro to the GST-fused i3 loop of the M3R. These
      results identify a novel molecular mechanism that can impart receptor subtype
      selectivity on signal transduction via Gq-coupled muscarinic receptors.

PMID- 19182867
TI  - Development of a simple low noise amplifier for recording of sensory mass signals
      from peripheral nerves.
AB  - In the present work, a simple low noise amplifier system with relatively few
      components for the recording of peripheral nerve signals via electrodes, such as
      cuff electrodes, was developed. The amplifier system was developed with the aid
      of a computer-aided characterization tool, which allowed the characterization of
      bioelectric signal amplifiers and the identification of system parameters. Three
      commercially available amplifier systems were investigated with this tool
      regarding their technical parameters. In addition, peripheral sensory nerve mass
      signals were analyzed to validate the target specifications for the amplifier to
      be designed with regard to amplitude and frequency range. An amplifier was
      designed and developed according to these specifications, characterized in
      comparison to the commercial amplifiers, and successfully applied in pilot
      experiments on the sciatic nerve in a rat animal model.

PMID- 19182868
TI  - Computer- and robot-assisted stereotaxy for high-precision small animal brain
      exploration.
AB  - This contribution introduces a computer- and robot-assisted framework for
      stereotactic neurosurgery on small animals. Two major elements of this framework
      are presented in detail: a robotic stereotactic assistant and the software
      framework for placement of probes into the brain. The latter integrates modules
      for registration, insertion control, and preoperative path planning. Two options
      for path planning are addressed: (a) atlas-based planning and (b) image-based
      planning based on computed tomography data. The framework is tested performing
      robot-assisted insertion of microelectrodes and acquisition of
      electrophysiological recordings in vivo. Concepts for data analysis pointing
      towards a mapping of position and neural structure to functional data are
      introduced. Results show that the presented framework allows precise small animal
      stereotaxy and therefore offers new options for brain research.

PMID- 19182869
TI  - Postoperative aqueous outflow in the human eye after glaucoma filtration surgery:
      biofluidmechanical considerations.
AB  - To evaluate the possible postoperative outflow from the anterior chamber of the
      eye after filtration surgery, a mathematical model based on fluid mechanical
      principles and clinical data is proposed. Two ophthalmic surgical procedures, non
      penetrating deep sclerectomy and trabeculectomy, were analyzed. Based on
      mathematical modeling, the amount of postoperative outflow through the fistula
      (after trabeculectomy) or membrane (after non-penetrating surgery) as well as the
      outflow through residual natural drainage pathways were calculated and compared.
      From our model, the following results were obtained: 1) if trabeculectomy is
      carried out in an eye with preoperative intraocular pressure (IOP) of 30 mm Hg
      and postoperative IOP=10 mm Hg, only 10% of aqueous utilizes the natural outflow
      pathway via the trabecular meshwork, whereas if non-penetrating surgery is
      carried out in the same eye with postoperative IOP=16 mm Hg, the outflow through
      the trabecular meshwork amounts to 35%. Thus, non-penetrating surgery provides
      more aqueous outflow along the natural outflow pathways than trabeculectomy. 2)
      Generally, the higher the postoperative IOP and/or the lower the preoperative
      IOP, the higher the amount of aqueous, which will utilize the natural outflow
      pathways postoperatively. 3) The reestablishment of aqueous production
      postoperatively in addition to other factors, such as wound healing, may be a
      reason for IOP increase during the postoperative period.

PMID- 19182870
TI  - [Intraoral diagnostics using confocal laser scanning microscopy].
AB  - The aim of this study was to analyze and evaluate the oral mucosa and the surface
      constitution of dental materials to display the characteristics and the behaviour
      of dental composites concerning the margin fit. Therefore, the gingiva and
      composite restorations of 45 patients aged 17-69 years were examined with a new
      digital confocal laser scanning microscope developed in Rostock. The device works
      in contact with the surface of the examination region using a water immersion
      objective and a diode laser with a wavelength of 670 nm. As a result of a PMMA
      Cap with a thickness of 0.5 mm, we can create images with exact depth information
      and of very good quality. The epithelium of the gingiva with its cellular and
      subcellular structures could be observed up to a depth of 200 microm. Also,
      papillary crests, blood vessels and even the blood flow were visible. An
      inflammation of the gingiva could be verified because of the existence of
      inflammatory cells. The enamel and dental restorations could be observed up to a
      depth of 80 microm and allowed the evaluation of the margin fit. Confocal laser
      scanning microscopy seems to be suitable for the non-invasive examination of oral
      mucosa and dental materials in vivo.

PMID- 19182871
TI  - Influence of gestational age on the effectiveness of spatial and temporal methods
      for the reconstruction of the fetal magnetocardiogram.
AB  - Fetal magnetocardiography (fMCG) has been shown to augment fetal ultrasound
      evaluation for high-risk conditions, but the clinical utility of fMCG depends on
      the reliability of the cardiac traces reconstructed. We performed a
      methodological study to examine the influence of gestational age on the
      properties of the fetal magnetocardiograms extracted with two methods of signal
      reconstruction: the template matching technique (TMT), which extracts the
      maternal components from the signal using only temporal information, and
      independent component analysis (ICA), which separates the fetal signals by using
      information on the spatial distribution of the mixed source signals in addition
      to higher order temporal statistics. Efficiency and accuracy were evaluated in
      terms of fetal beat detection, signal characteristics, and duration of cardiac
      time intervals (CTIs) on the averaged traces. ICA outperformed TMT with regard to
      beat detection and signal-to-noise ratio. The timing of the heartbeats and the
      duration of the CTIs were essentially the same, whereas some alterations in
      signal morphology were observed in the ICA traces. We conclude that ICA may be
      useful in early gestation when the signals are noisy, while TMT may be preferred
      when accurate beat morphology is required for diagnostic purposes.

PMID- 19182872
TI  - [Fluid studies on flow behaviour in narrowing vessels with PC-velocimetry and
      numerical simulations].
AB  - BACKGROUND: Fluid dynamics play an important role in arterial diseases. PC
      velocimetry as a magnetic resonance (MR) method is a useful tool for the
      examination of blood vessels, in particular in haemodynamics and morphology. Due
      to signal loss caused by turbulent flow, classification of stenoses remains
      difficult. In the presence of metallic stents, susceptibility effects and RF
      artefacts further deteriorate image quality. MATERIALS AND METHODS: Regarding
      fluid dynamics, stenosis, stent and restenosis (i.e., re-closing of the vessel in
      areas with stents) have similar properties: the flow close to an obstacle is
      accelerated and after a specific length, the so-called reattachment length, it
      redevelops into its original flow profile. Depending on the shape of the obstacle
      and its reattachment length, a method is developed to classify stenosis using MR
      imaging. Enlarged, simplified stenosis models (phantoms) were examined and were
      also modelled using computational fluid dynamics (CFD). RESULTS: MR- and CFD
      measurements show influences of the stenosis shape, especially the diameter. In
      graphical analysis (streamline and vector plots), a reattachment length of
      6.7xstep size could be determined under laminar conditions and nonpulsatile flow.
      DISCUSSION: Stenosis and other narrowing of vessels are classifiable more exactly
      using PC-velocimetry. From the flow behaviour in the area around the narrowing of
      the vessel wall, the character of the stenosis can be derived. But more
      parameters, as bended vessel shapes, pulsated flow, non-Newtonian flow behaviour
      as well as elastic properties of the vessels need to be incorporated.

PMID- 19182873
TI  - Post-processing technique for improved assessment of hard tissues in the
      submicrometer domain using local synchrotron radiation-based computed tomography.
AB  - During the last two decades micro-computed tomography has become the method of
      choice for the non-destructive assessment and quantitative morphometry of hard
      tissues in three dimensions. With the advent of third-generation synchrotron
      radiation sources, micro-computed tomography in the micrometer range has become
      feasible and has been employed to analyze local bone tissue properties. However,
      owing to limitations regarding the tradeoff between object size and spatial
      resolution, non-destructive conventional global computed tomography of hard
      tissues, such as bone, remains unachievable in the submicrometer domain so far.
      Here, we report on a post-processing technique for the assessment of hard tissues
      using local synchrotron radiation-based computed tomography, which overcomes this
      experimental limitation.

PMID- 19182879
TI  - Delphinidin modulates the DNA-damaging properties of topoisomerase II poisons.
AB  - The anthocyanidin delphinidin (DEL) has recently been shown to inhibit human
      topoisomerase I and II, without stabilizing the covalent DNA/topoisomerase
      intermediate [Habermeyer, M., Fritz, J., Barthelmes, H. U., Christensen, M. O.,
      Larsen, M. K., Boege, F., and Marko, D. (2005) Anthocyanidins modulate the
      activity of human DNA topoisomerases I and II and affect cellular DNA integrity.
      Chem. Res. Toxicol. 18, 1395-404]. In the present study, we demonstrated that DEL
      affects the catalytic activity of topoisomerase IIalpha in a redox-independent
      manner. Furthermore, this potent inhibitory effect is not limited to a cell-free
      system, but is also of relevance within intact cells. DEL at micromolar
      concentrations was found to significantly decrease the level of topoisomerase
      IIalpha/DNA intermediates stabilized by the topoisomerase II poison doxorubicin
      in the human colon carcinoma cell line (HT29). In addition, DEL diminished the
      DNA-damaging properties of topoisomerase II poisons in HT29 cells without
      affecting the level of sites sensitive to formamidopyrimidine-DNA-glycosylase.
      However, the preventive effect on DNA damage exhibited an apparent maximum at a
      concentration of 10 microM DEL, followed by a recurrence of DNA damage at higher
      DEL concentrations. Furthermore, the incubation of HT29 cells with 10 microM DEL
      resulted in a decrease of etoposide (ETO)-induced DNA strand breaks. However, the
      level of ETO-stabilized covalent topoisomerase/DNA intermediates did not affect
      DEL, indicating an additional mechanism of action. An impact of DEL on genes
      involved in the repair of DNA double-strand breaks and the onset of apoptosis has
      to be considered. In conclusion, the natural food constituent DEL represents,
      depending on the concentration range, a protective factor against the DNA
      damaging effects of topoisomerase II poisons in vitro. Further studies are needed
      to clarify whether in vivo a high DEL intake might compromise the therapeutic
      outcome of these anticancer agents.

PMID- 19182886
TI  - Copper oxide nanoparticle-catalyzed coupling of diaryl diselenide with aryl
      halides under ligand-free conditions.
AB  - A new, efficient and ligand-free cross-coupling reaction of aryl halides and
      diaryl diselenides using a catalytic amount of nanocrystalline CuO as a
      recyclable catalyst with KOH as the base in DMSO at 110 degrees C is reported.
      This protocol has been utilized for the synthesis of a variety of aryl selenides
      in excellent yields from the readily available aryl halides and diaryl
      diselenides.

PMID- 19182889
TI  - A study of the epoxidation of cycloolefins by the t-BuOH copper-permanganate
      system.
AB  - Evidence is presented that Cu(MnO(4))(2) effectively epoxidizes trisubstituted
      steroid olefins by a nonconcerted pathway.

PMID- 19182890
TI  - Microplate-based characterization of protein-phosphoinositide binding
      interactions using a synthetic biotinylated headgroup analogue.
AB  - Membrane lipids act as important regulators of a litany of important
      physiological and pathophysiological events. Many of them act as site-specific
      ligands for cytosolic proteins in binding events that recruit receptors to the
      cell surface and control both protein function and subcellular localization.
      Phosphatidylinositol phosphates (PIP(n)s) are a family of signaling lipids that
      regulate numerous cellular processes by interacting with a myriad of protein
      binding modules. Characterization of PIP(n)-binding proteins has been hampered by
      the lack of a rapid and convenient quantitative assay. Herein, microplate-based
      detection is presented as an effective approach to characterizing protein-PIP(n)
      binding interactions at the molecular level. With this assay, the binding of
      proteins to isolated PIP(n) headgroups is detected with high sensitivity using a
      platform that is amenable to high-throughput screening. In the studies described
      herein, biotinylated PI-(4,5)-P(2) headgroup analogue 1 was designed,
      synthesized, and immobilized onto 96-well streptavidin-coated microplates to
      study receptor binding. This assay was used to characterize the binding of the PH
      domain of beta-spectrin to this headgroup. The high affinity interaction that was
      detected for surface association (K(d, surf) = 6 nM +/- 3), demonstrates that
      receptor binding modules can form high affinity interactions with lipid
      headgroups outside of a membrane environment. The results also indicate the
      feasibility of the assay for rapid characterization of PIP(n)-binding proteins as
      well as the promise for high-throughput analysis of protein-PIP(n) binding
      interactions. Finally, this assay was also employed to characterize the
      inhibition of the binding of receptors to the PIP(n)-derivatized microplates
      using solution phase competitors. This showcases the viability of this assay for
      rapid screening of inhibitors of PIP(n)-binding proteins.

PMID- 19182891
TI  - Innovative approach for producing injectable, biodegradable materials using
      chitooligosaccharides and green chemistry.
AB  - Although there are a number of injectable biomaterials currently under
      development, they present some drawbacks such as being based on synthetic
      polymers, needing toxic or aggressive synthesis procedures or using raw materials
      with low availability and/or high production costs. Having this in mind, a novel
      injectable biomaterial using chitooligosaccharides as starting materials was
      developed. This system uses a widely available and cheap polymer from marine
      biomass (chitosan), which can be turned into an injectable material by water
      based and ecologically friendly reactions. Chitooligosaccharides were
      functionalized with methacrylic groups, to allow in situ cross-linking. The
      degree of substitution, as determined by (1)H NMR, varied between 5 and 50%. The
      system was characterized in terms of kinetics of gel formation, rheology,
      degradation behavior and in vitro cytotoxicity. The gelation time could be easily
      tailored between 1.5 and 60 min by changing the conditions of the methacrylation
      reaction, and the final gel presented rheological properties typical of strong
      gels, that is, shear stresses in the kPa range. The cross-linked gel was
      degradable and nontoxic, presenting indeed an interesting cytokinetic effect.
      Injectable materials based on chitooligosaccharides are, therefore, an innovative
      system combining adequate biological performance, ease of preparation, and an
      ecologically friendly concept of production.

PMID- 19182897
TI  - Expansile nanoparticles: synthesis, characterization, and in vivo efficacy of an
      acid-responsive polymeric drug delivery system.
AB  - Nanoparticles are finding increased uses in drug delivery applications as a means
      to increase treatment efficacy and improve patient care. Here, we report
      engineered polymeric nanoparticles that undergo a hydrophobic to hydrophilic
      transition at pH 5 to afford swelling and rapid release of their contents. As our
      clinical interest lies in the prevention of lung tumor recurrence following
      resection, the nanoparticles were evaluated in a model mimicking microscopic
      disease, akin to residual occult tumor that can remain at the resection margin
      following surgery. Expansile nanoparticles loaded with paclitaxel, a poorly water
      soluble anticancer drug, prevent establishment of lung cancer in vivo and are
      superior to the conventional drug delivery method for paclitaxel using Cremophor
      EL/ethanol.

PMID- 19182898
TI  - In situ monitoring of conformational changes of and peptide bindings to
      calmodulin on a 27 MHz quartz-crystal microbalance.
AB  - Conformational changes of calmodulin (CaM) by additions of Ca(2+) ions and
      bindings of CaM-binding peptides to Ca(2+)/CaM followed by conformational changes
      were monitored by a CaM-immobilized 27 MHz quartz-crystal microbalance (QCM) with
      an admittance analysis. Both the binding and the conformational change events
      could be detected from the time-dependence of frequency decreases (mass
      increases) and energy dissipation decreases (elasticity increases), respectively.
      When Ca(2+) ions were injected to a QCM cell on which biotinylated CaM was
      immobilized with avidin-biotin interactions, a frequency increase (a mass
      decrease) and an energy dissipation decrease (an elasticity increase) were
      observed because of the dehydration and the elasticity increase caused by
      conformational changes from the flexible CaM to the rigid Ca(2+)/CaM exposing the
      hydrophobic surface. In the case of the addition of CaMKII-peptide in the
      Ca(2+)/CaM-immobilized QCM, the immediate frequency decrease (the mass increase)
      due to the binding of the peptide to Ca(2+)/CaM and the following energy
      dissipation decrease (the elasticity increase) with a time lag were observed.
      This suggests that the interaction of the CaMKII-peptide to Ca(2+)/CaM follows an
      allosteric binding mode. Binding kinetics of the peptide to Ca(2+)/CaM (k(1) and
      k(-1)) and kinetics of the following conformational change of Ca(2+)/CaM (k(2)
      and k(-2)) could be obtained. This technique is useful to investigate
      biomolecular interactions involving the conformational and/or viscoelastic
      property changes that are biologically important.

PMID- 19182899
TI  - Binding of indanocine to the colchicine site on tubulin promotes fluorescence,
      and its binding parameters resemble those of the colchicine analogue AC.
AB  - Indanocine, a synthetic indanone, has shown potential antiproliferative activity
      against several tumor types. It is different from many other microtubule
      disrupting drugs, because it displays toxicity toward multidrug resistance cells.
      We have examined the interaction of indanocine with tubulin and determined their
      binding and thermodynamic parameters using isothermal titration calorimetry
      (ITC). Indanocine is weakly fluorescent in aqueous solution, and the binding to
      tubulin enhances fluorescence with a large blue shift in the emission maxima.
      Indanocine binds to the colchicine site of tubulin, although it bears no
      structural similarity with colchicine. Nevertheless, like colchicine analogue AC,
      indanocine is a flexible molecule in which two halves of the molecule are
      connected through a single bond. Also, like AC, indanocine binds to the
      colchicine binding site of tubulin in a reversible manner and the association
      reaction occurs at a faster rate compared to that of colchicine-tubulin binding.
      The binding kinetics was studied using stopped-flow fluorescence. The association
      process follows biphasic kinetics similar to that of the colchicine-tubulin
      interaction. The activation energy of the reaction was 10.5 +/- 0.81 kcal/mol.
      Further investigation using ITC revealed that the enthalpy of association of
      indanocine with tubulin is negative and occurs with a negative heat capacity
      change (DeltaC(p) = -175.1 cal mol(-1) K(-1)). The binding is unique with a
      simultaneous participation of both hydrophobic and hydrogen bonding forces.
      Finally, we conclude that even though indanocine possesses no structural
      similarity with colchicine, it recognizes the colchicine binding site of tubulin
      and its binding properties resemble those of the colchicine analogue AC.

PMID- 19182900
TI  - Early intraplatelet signaling enhances the release of human platelet PAR-1 and -4
      amino-terminal peptides in response to thrombin.
AB  - Activation of washed human platelets initiated with alpha-thrombin, SFLLRN, or
      AYPGKF invariably results in the generation of PAR-1-(1-41) and PAR-4-(1-47). PAR
      1-(1-41) and PAR-4-(1-47) are amino-terminal peptides generated when PAR-1 and -4
      are cleaved in their first extracellular domains after R(41) and R(47),
      respectively, to expose the tethered ligand domains of PAR-1 and -4. Since
      soybean trypsin inhibitor decreases generation of PAR-1-(1-41) and PAR-4-(1-47)
      and other platelet aggregation-related responses to these three agonists, but
      does not inactivate alpha-thrombin, a platelet trypsin-like proteinase apparently
      activates PAR-1 and -4 to propagate PAR-dependent platelet responses. This study
      identified the signaling pathways implicated in the generation of the platelet
      proteinase that in turn produces PAR-1-(1-41) and PAR-4-(1-47), to thereby drive
      the subsequent PAR-dependent platelet aggregation-related responses to alpha
      thrombin, SFLLRN, or AYPGKF. Only inhibitors of signaling enzymes that prevented
      ATP release (forskolin, PGE(1), or BIMI-1) prevented or delayed the generation of
      PAR-1-(1-41) and PAR-4-(1-47) in response to all three agonists. SBTI prevented
      platelet aggregation initiated by alpha-thrombin, SFLLRN, or AYPGKF but did so
      less effectively when it was added 10 s after each agonist. Thus, the platelet
      derived proteinase acts within 10 s of each agonist addition to generate PAR-1-(1
      41) and PAR-4-(1-47). Furthermore, alpha-thrombin may not effectively catalyze
      PAR-1-(1-41) and PAR-4-(1-47) generation. We propose that unidentified ATP
      dependent phosphorylation reactions catalyzed by PKC help to generate the
      platelet-derived proteinase that propagates human platelet PAR-1 and -4
      activation by the three agonists.

PMID- 19182901
TI  - Self-assembly of collagen peptides into microflorettes via metal coordination.
AB  - The self-assembly of synthetic biomaterials, such as collagen peptides, can be
      harnessed for a range of biomedical applications. In an effort to obtain collagen
      based macromolecular assemblies with temporal control, we designed a system that
      assembled only in the presence of external stimuli. We report a collagen triple
      helical peptide that is modified with a His(2) moiety on its C-terminus and a
      nitrilotriacetic acid unit on its N-terminus that rapidly and reversibly
      assembles in the presence of metal ions. Dynamic light scattering and turbidity
      experiments confirmed the presence of higher order aggregates in solution upon
      the introduction of Zn(2+), Cu(2+), Ni(2+), and Co(2+). This assembly process was
      found to be fully reversible using EDTA as a metal ion chelator. Control peptides
      that contain only a single ligand-modified terminus were not responsive to the
      same metal ions, thus demonstrating the requirement of both ligand modifications
      for peptide assembly. Scanning electron microscopy imaging of the peptide-metal
      assemblies revealed micrometer-sized florettes in addition to curved, stacked
      sheets. More detailed analysis of the Zn(2+)-generated microflorettes showed that
      the surface of these particles contains ruffled structures with a highly dense
      surface area. Potential folding intermediates in the formation of the
      microflorettes were observed at lower temperatures and at early time points in
      the assembly that are composed of curved layered sheets. Significantly, the
      assembly process proceeded under mild conditions using neutrally buffered aqueous
      solution at room temperature. These microscopic structures offer opportunities in
      many areas, including drug delivery, tissue engineering, and regenerative
      medicine.

PMID- 19182902
TI  - Kinetic isotope effects in hydroxylation reactions effected by cytochrome P450
      compounds I implicate multiple electrophilic oxidants for P450-catalyzed
      oxidations.
AB  - Kinetic isotope effects were measured for oxidations of (S,S)-2-(p
      trifluoromethylphenyl)cyclopropylmethane containing zero, two, and three
      deuterium atoms on the methyl group by Compounds I from the cytochrome P450
      enzymes CYP119 and CYP2B4 at 22 degrees C. The oxidations displayed saturation
      kinetics, which permitted solution of both binding constants (K(bind)) and first
      order oxidation rate constants (k(ox)) for both enzymes with the three
      substrates. The binding constant for CYP2B4 Compound I was about 1 order of
      magnitude greater than that for CYP119 Compound I, but the oxidation rate
      constants were similar for the two. In oxidations of 1-d(0), k(ox) = 10.4 s(-1)
      for CYP119 Compound I, and k(ox) = 12.4 s(-1) for CYP2B4 Compound I. Primary
      kinetic isotope effects (P) and secondary kinetic isotope effects (S) were
      obtained from the results with the three isotopomers. The primary KIEs were
      large, P = 9.8 and P = 8.9 for CYP119 and CYP2B4 Compounds I, respectively, and
      the secondary KIEs were small and normal, S = 1.07 and S = 1.05, respectively.
      Large intermolecular KIEs for 1-d(0) and 1-d(3) of k(H)/k(D) = 11.2 and 9.8 found
      for the two Compounds I contrast with small intermolecular KIEs obtained
      previously for the same substrate in P450-catalyzed oxidations; these differences
      suggest that a second electrophilic oxidant, presumably iron-complexed hydrogen
      peroxide, is important in cytochrome P450 oxidations under turnover conditions.

PMID- 19182903
TI  - Design of SERS-encoded, submicron, hollow particles through confined growth of
      encapsulated metal nanoparticles.
AB  - The synthetic architectures of complex inorganic nanostructures, including
      multifunctional hollow capsules, are expected to play key roles in many different
      applications, such as drug delivery, photonic crystals, nanoreactors, and
      sensing. Implementation of novel strategies for the fabrication of such materials
      is needed because of the infancy of this knowledge, which still limits progress
      in certain areas. Herein we report a straightforward synthetic approach for the
      development of multifunctional submicron reactors comprising catalytic gold
      nanoparticles (2-3 nm) confined inside hollow silica capsules. Additionally, the
      confined growth of encapsulated metal nanoparticles was carried out to evidence
      the usefulness and functionality of these reactors in catalytic applications and
      as an approach for the development of novel complex nanostructures. Their
      potential and multifunctionality have been pointed out by fabrication of SERS
      encoded submicrometer particles with shape and size uniformity for use in antigen
      biosensing; this was accomplished via codification of gold nanoparticle islands
      grown onto their inner surfaces.

PMID- 19182906
TI  - Pressurized liquid in nanopores: a modified Laplace-Young equation.
AB  - In the current study, we analyze the motion of pressurized water molecules in
      nanopores of a well-crystallized, hydrophobic zeolite using both experiment and
      molecular dynamics simulation. It is discovered that, contradictory to the
      prediction of the classic Laplace-Young equation, the required infiltration
      pressure is highly dependent on the infiltration volume. A modified Laplace-Young
      equation is developed to take into consideration the effective solid-liquid
      interfacial tension, the thermal energy exchange, as well as the variation in
      configuration of confined liquid molecules. The last two factors are significant
      only when the nanopore diameter is comparable with the liquid molecule size. It
      is also remarkable that the infiltrated liquid molecules, when confined in the
      nanoenvironment, could transform from a single-chain conformation to a double
      helical structure as the pressure increases, accompanied by an abrupt system free
      energy change that leads to different pressure-induced transport behaviors.

PMID- 19182904
TI  - Isolation of mammalian 26S proteasomes and p97/VCP complexes using the ubiquitin
      like domain from HHR23B reveals novel proteasome-associated proteins.
AB  - Recent studies, mainly in yeast, have identified various cofactors that associate
      with the 26S proteasome and appear to influence its function. To identify these
      proteins in different cells and physiological states, we developed a method to
      gently and rapidly isolate 26S proteasomes and associated proteins without the
      need for genetic modifications of the proteasome. This method is based on the
      affinity of this complex for the ubiquitin-like (UBL) domain of hHR23B and
      elution with a competing polypeptide containing a ubiquitin-interacting motif.
      Associated with 26S proteasomes from rat muscle were a variety of known
      proteasome-interacting proteins, activators, and ubiquitin conjugates. In
      addition, we identified over 40 proteins not previously known to associate with
      the 26S proteasome, some of which were tightly associated with the proteasome in
      a substoichiometric fashion, e.g., the deubiquitinating enzymes USP5/isopeptidase
      T and USP7/HAUSP and the ubiquitin ligases ARF-BP1/HUWE1 and p600/UBR4. By
      altering buffer conditions, we also purified by this approach complexes of the
      ATPase p97/VCP associated with its adaptor proteins Ufd1-Npl4, p47, SAKS1, and
      FAF1, all of which contain ubiquitin-binding motifs. These complexes were
      isolated with ubiquitin conjugates bound and were not previously known to bind to
      the UBL domain of hHR23B. These various UBL-interacting proteins, dubbed the UBL
      interactome, represent a network of proteins that function together in ubiquitin
      dependent proteolysis, and the UBL method offers many advantages for studies of
      the diversity, functions, and regulation of 26S proteasomes and p97 complexes
      under different conditions.

PMID- 19182908
TI  - Super-resolution without evanescent waves.
AB  - The past decade has seen numerous efforts to achieve imaging resolution beyond
      that of the Abbe-Rayleigh diffraction limit. The main direction of research
      aiming to break this limit seeks to exploit the evanescent components containing
      fine detail of the electromagnetic field distribution at the immediate proximity
      of the object. Here, we propose a solution that removes the need for evanescent
      fields. The object being imaged or stimulated with subwavelength accuracy does
      not need to be in the immediate proximity of the superlens or field concentrator:
      an optical mask can be designed that creates constructive interference of waves
      known as superoscillation, leading to a subwavelength focus of prescribed size
      and shape in a field of view beyond the evanescent fields, when illuminated by a
      monochromatic wave. Moreover, we demonstrate that such a mask may be used not
      only as a focusing device but also as a super-resolution imaging device.

PMID- 19182909
TI  - Detection of mycoestrogen zearalenone by a molecularly imprinted polypyrrole
      based surface plasmon resonance (SPR) sensor.
AB  - The aim of the present work was to investigate the feasibility of employing the
      molecular imprinting polymer technique for detecting the mycotoxin zearalenone
      using a surface plasmon resonance (SPR) transducer. The molecularly imprinted
      polypyrrole (MIPPy) film was prepared by electropolymerization of pyrrole onto
      the bare Au chip in the presence of a template zearalenone molecule. The MIPPy
      SPR sensor exhibited a linear response in the range of 0.3-3000 ng/mL (R (2) =
      0.993) for detection of zearalenone. The selectivity efficiencies of zearalenone
      and other structurally related analogues were 1.0 and 0.15-0.27, respectively.
      The limit of detection and average recovery of blank corn matrix spiked with 30
      ng/g zearalenone were 0.3 ng/g and 89%, respectively, and these were found to be
      comparable to those obtained by enzyme-linked immunosorbent assay. These results
      suggest that a combination of SPR sensing with MIPPy film is a promising
      alternative method for the detection of zearalenone.

PMID- 19182911
TI  - Transport through a single octanethiol molecule.
AB  - Octanethiol molecules adsorbed on Pt chains are studied with scanning tunneling
      microscopy and spectroscopy at 77 K. The head of the octanethiol binds to a Pt
      atom and the tail is lying flat down on the chain. Open-loop current time traces
      reveal that the molecule wags its tail and attaches to the scanning tunneling
      microscopy-tip resulting in a dramatic increase of the current. We measured a
      single molecule resistance of 100-150 Mohms.

PMID- 19182912
TI  - Raman topography and strain uniformity of large-area epitaxial graphene.
AB  - We report results of Raman spectroscopy studies of large-area epitaxial graphene
      grown on SiC. Our work reveals unexpectedly large variation in Raman shift
      resulting from graphene strain inhomogeneity, which is shown to be correlated
      with physical topography by coupling Raman spectroscopy with atomic force
      microscopy. We show that graphene strain can vary over a distance shorter than
      300 nm and may be uniform only over roughly 1 microm. We show that nearly strain
      free graphene is possible even in epitaxial graphene.

PMID- 19182914
TI  - Preparation and antioxidant activity of green tea extract enriched in
      epigallocatechin (EGC) and epigallocatechin gallate (EGCG).
AB  - The present study investigated effects of solvents, temperature, and duration on
      extracting efficiency of catechins from green tea by an orthogonal test. The
      results suggested that extraction of epigallocatechin gallate (EGCG) was highly
      dependent on these factors, whereas that of epigallocatechin (EGC) was
      significantly affected by duration and solvent (P < 0.05). Effects of these
      factors on epicatechin (EC), catechin (C), and epicatechin gallate (ECG) were not
      significant. A two-step preparation was adopted to produce green tea extract
      enriched in EGC (GTE-EGC) and green tea extract enriched in EGCG (GTE-EGCG). The
      optimum conditions for GTE-EGC were that green tea was brewed in 75% ethanol at
      30 degrees C for 10 min, whereas for GTE-EGCG the same tea was brewed in 35%
      ethanol at 90 degrees C for 60 min. Compared with GTE-EGC, GTE-EGCG had EGCG
      increased by 110.42%, whereas EGC decreased by 40.38% with EC and ECG being
      unchanged. Most importantly, GTE-EGCG possessed greater antioxidant activity (in
      vitro) than GTE-EGC.

PMID- 19182913
TI  - Changes in lipid metabolism by soy beta-conglycinin-derived peptides in HepG2
      cells.
AB  - In this study, HepG2 cells were treated with short peptides (7S-peptides) derived
      from highly purified soybean beta-conglycinin (7S), which was free from
      lipophilic protein, and the effect of the peptide treatment on lipid metabolism
      was determined. 7S-peptide treatment suppressed the secretion of apolipoprotein B
      100 from HepG2 cells into the medium. The 7S-peptides also suppressed the
      incorporation of (3)H-glycerol and (14)C-acetate into triacylglyceride but not
      into major phospholipids, such as phosphatidylcholine and
      phosphatidylethanolamine. Additionally, the synthesis of cholesterol esters was
      dramatically decreased for 2 h after the addition of the 7S-peptides, whereas the
      synthesis of cholesterol remained unchanged by 4 h and increased by 8 h after the
      addition of the 7S-peptides. The cleaved nuclear form of SREBP-2 increased 8 h
      after the addition of the 7S peptides, suggesting a decrease in intracellular
      cholesterol levels. Analysis of changes in mRNA expression after 7S-peptide
      treatment suggested that the 7S-peptides lower the level of cholesterol in the
      endoplasmic reticulum, increase the mRNA of genes related to beta-oxidation of
      fatty acids, and increase the synthesis of cholesterol. From these results, it
      may be concluded that the peptides derived from 7S altered the lipid metabolism
      to decrease secretion of apolipoprotein B-100-containing lipoprotein from HepG2
      cells.

PMID- 19182915
TI  - Efficient nucleophilic fluoromethylation and subsequent transformation of alkyl
      and benzyl halides using fluorobis(phenylsulfonyl)methane.
AB  - An efficient methodology for the nucleophilic fluoromethylation of alkyl and
      benzyl halides using alpha-fluoro-alpha-(phenylsulfonyl)methane (1) as a highly
      versatile reagent is reported. Using benzyl halides, stereospecific one-pot
      synthesis of alpha-fluorovinyl compounds such as alpha-fluorostyrylsulfones,
      alpha-fluorocinnamates, and alpha-fluorochalcones has been achieved. The
      methodology has been extended toward the synthesis of alpha-substituted
      fluoroalkane derivatives using selective reductive desulfonylation conditions.

PMID- 19182916
TI  - Human herpesvirus 8 DNA load in the leukocytes correlates with the platelet
      counts in HIV type 1-infected individuals.
AB  - Abstract Human herpes virus 8 (HHV-8) is known to be reactivated in
      immunocompromised situations and it is associated with Kaposi's sarcoma (KS) and
      some hematological diseases. The aim of this study was to analyze the effect of
      HHV-8 on HIV-1 infection, especially on thrombocytopenia complicated with HIV
      infection. The HHV-8 DNA load was determined by a quantitative real-time PCR,
      using leukocytes from 125 HIV-1-infected individuals. HHV-8 DNA was detected in
      37 individuals. The increased HIV-1 load and reduced percentage of CD4-positive T
      cells were significantly associated with the presence of HHV-8. The prevalence
      and load for HHV-8 are higher in patients with KS than in patients without KS,
      but the difference is not significant. The increased HHV-8 DNA load was
      significantly correlated with thrombocytopenia, and platelet counts were
      significantly lower in individuals with HHV-8 than in individuals without HHV-8.
      We also obtained the negative correlations between changes in platelet counts and
      changes in HHV-8 DNA loads. The association between thrombocytopenia and HHV-8
      has never been reported previously, apart from some case reports of Castleman's
      disease and KS. Various cytokines or chemokines are produced by HHV-8-infected
      cells, some of which have been reported to inhibit hematopoiesis. This may be one
      of the mechanisms by which HHV-8 infection induces thrombocytopenia. These
      results indicate that HHV-8 DNA in leukocytes may provide useful information for
      the assessment of the clinical appearance of HIV-1 infection.

PMID- 19182918
TI  - Genetic analysis of HIV type 1 strains from newly infected untreated patients in
      cyprus: high genetic diversity and low prevalence of drug resistance.
AB  - Abstract The molecular epidemiology of HIV-1 infection was first studied in
      Cyprus in the mid-1990s, but the extent of HIV-1 diversity and the prevalence of
      drug resistance have remained elusive. In an effort to address this issue, the
      present study examined HIV-1 strains isolated from 37 newly diagnosed untreated
      HIV-1 patients, representing 72% of the total number of newly diagnosed and drug
      naive patients in the period 2003 to 2006. DNA sequences encoding the gag (p17,
      p24, p2, p7, p1, and p6), pol (protease and reverse transcriptase), and env
      (gp160) regions were amplified by RT-PCR from plasma HIV-1 RNA from all patients
      and sequenced using a newly designed methodology. All amplified products were
      studied according to established genetic methodologies to determine the genetic
      subtype and the prevalence of drug-resistance-associated mutations to currently
      available antiretroviral drugs. Analyses of the obtained viral sequences
      indicated that subtype A was the most common subtype present and accounted for
      38% of the infections followed by subtype B (35%), subtype C (13%), CRF02_AG
      (8%), and subtypes D and CRF01_AE (3% each). One patient (2.7%) had an M41L/M and
      another patient (2.7%) an M184V amino acid substitution in the reverse
      transcriptase (RT) associated with high-level resistance to RT inhibitors. There
      were no patients with resistant mutations to protease inhibitors (PI).
      Additionally, one patient (2.7%) had an L44M amino acid substitution within the
      HR1 region of gp41 conferring resistance to the enfuvirtide (T20) fusion
      inhibitor. Similar to results of the 1994 molecular epidemiological study, these
      data demonstrate the extensive heterogeneity of HIV-1 infection in Cyprus and the
      low prevalence of transmitted resistance to current HIV-1 antiretroviral drugs.
      Taken together, these findings demonstrate that HIV-1 infection in Cyprus is
      being replenished by a continuous influx of new strains from many countries,
      establishing an ever-evolving and polyphyletic infection in the island.

PMID- 19182919
TI  - Clinical differences and viral diversity between newly HIV type 1-diagnosed
      African and non-African patients in Spain (2005-2007).
AB  - Abstract The diagnosis of HIV-1 is increasing in African-born persons residing in
      Europe. They present a high prevalence of HIV-1 non-B variant infections and of
      parasitic infections, both of which are infrequent in Western countries.
      Immigration favors their presence in nonendemic countries. In this study, all
      newly HIV-diagnosed individuals at an HIV/AIDS and Tropical Medicine reference
      center in Madrid from 2005 through 2007 were retrospectively studied. HIV-1
      subtyping was performed in gag, pol, and gp41 coding regions by phylogenetic
      analyses. The presence of other pathogens was also evaluated. Furthermore, all
      HIV-1-infected Africans were screened for parasitic infections. Newly diagnosed
      HIV-1 subjects included 90 sub-Saharan Africans and 188 non-Africans (116
      Spaniards, 13 other Europeans, and 59 Latin Americans). Significantly higher
      numbers of HIV-1-infected Africans than non-Africans were females, acquired HIV-1
      by heterosexual contact, and presented a more advanced clinical CDC stage and
      criteria for starting antiretroviral therapy in the first clinical visit. They
      predominantly carried non-B subtype infections, mainly intersubtype recombinants.
      Half of HIV-1-infected Africans had parasitic infections. CD4(+) T cell counts
      were lower among Africans than Europeans at the time of HIV-1 diagnosis. At 12
      months of follow-up after starting antiretroviral treatment, a significantly
      lower proportion of Africans than non-Africans achieved undetectable viremia due
      to their higher loss to follow-up. However, CD4(+) T cell recovery and
      virological failure rates were similar. Therefore, the profile of African HIV-1
      infected immigrants varies widely with respect to Spanish HIV-infected
      individuals. More advanced immunodeficiency and the coexistence of parasitic
      diseases and infections with a large diversity of HIV-1 non-B and recombinant
      variants are expected.

PMID- 19182920
TI  - Identification and characterization of CRF02_AG, CRF06_cpx, and CRF09_cpx
      recombinant subtypes in Mali, West Africa.
AB  - Abstract Multiple HIV-1 subtypes and circulating recombinant forms (CRFs) are
      known to cocirculate in Africa. In West Africa, the high prevalence of CRF02_AG,
      and cocirculation of subtype A, CRF01_AE, CRF06_cpx, and other complex
      intersubtype recombinants has been well documented. Mali, situated in the heart
      of West Africa, is likely to be affected by the spread of recombinant subtypes.
      However, the dynamics of the spread of HIV-1 recombinant subtypes as well as
      nonrecombinant HIV-1 group M subtypes in this area have not been systematically
      assessed. Herein, we undertook genetic analyses on full-length env sequences
      derived from HIV-1-infected individuals living in the capital city of Mali,
      Bamako. Of 23 samples we examined, 16 were classified as CRF02_AG and three had a
      subsubtype A3. Among the remaining HIV-1 strains, CRF06_cpx and CRF09_cpx were
      each found in two patients. Comparison of phylogenies for six matched pol and
      full-length env sequences revealed that two strains had discordant subtype/CRF
      designations between the pol and env regions: one had A3(pol)CRF02_AG(env) and
      the other had CRF02_AG(pol)A3(env). Taken together, our study demonstrated the
      high prevalence of CRF02_AG and complexity of circulating HIV-1 strains in Mali.
      It also provided evidence of ongoing virus evolution of CRF02_AG, as illustrated
      by the emergence of more complex CRF02_AG/A3 intersubtype recombinants in this
      area.

PMID- 19182921
TI  - Dynamics of NRTI resistance mutations during therapy interruption.
AB  - Abstract To date, very little information is available regarding the evolution of
      drug resistance mutations during treatment interruption (TI). Using a survival
      analysis approach, we investigated the dynamics of mutations associated with
      resistance to nucleoside analogue reverse transcriptase inhibitors (NRTIs) during
      TI. Analyzing 132 patients having at least two consecutive genotypes, one at last
      NRTI-containing regimen failure, and at least one during TI, we observed that the
      NRTI resistance mutations disappear at different rates during TI and are lost
      independently of each other in the majority of patients. The disappearance of the
      K65R and M184I/V mutations occurred in the majority of patients, was rapid, and
      was associated with the reemergence of wild-type virus, thus showing their
      negative impact on viral fitness. Overall, it seems that the loss of NRTI drug
      resistance mutations during TI is not an ordered process, and in the majority of
      patients occurs without specific interaction among mutations.

PMID- 19182917
TI  - An 11-Year Surveillance of HIV Type 1 Subtypes in Nagoya, Japan.
AB  - Abstract To monitor active HIV-1 transmission in Nagoya, Japan, we have been
      determining the subtypes of HIV-1 infecting therapy-naive individuals who have
      newly visited the Nagoya Medical Center since 1997. The subtypes were determined
      by phylogenetic analyses using the base sequences in three regions of the HIV-1
      genes including gag p17, pol protease (PR) and reverse transcriptase (RT), and
      env C2V3. Almost all HIV-1 subtypes from 1997 to 2007 and 93% of all HIV-1
      isolates in 2007 were subtype B. HIV-1 subtypes A, C, D, and F have been detected
      sporadically since 1997, almost all in Africans and South Americans. The first
      detected circulating recombinant form (CRF ) was CRF01_AE (11-year average annual
      detection rate, 7.7%). Only two cases of CRF02_AG were detected in 2006. A unique
      recombinant form (URF ) was first detected in 1998 and the total number of URFs
      reached 25 by year 2007 (average annual detection rate, 4.7%). Eleven of these 25
      were detected from 2000 to 2005 and had subtypes AE/B/AE as determined by base
      sequencing of the gag p17, pol PR and RT, and env C2V3 genes (average annual
      detection rate, 3.7%). Unique subtype B has been detected in six cases since
      2006. All 17 of these patients were Japanese. Other recombinant HIV-1s have been
      detected intermittently in eight cases since 1998. During the 11-year
      surveillance, most HIV-1s in Nagoya, Japan were of subtype B. We expect that
      subtype B HIV-1 will continue to predominate for the next several years. Active
      recombination between subtype B and CRF01_AE HIV-1 and its transmission were also
      shown.

PMID- 19182922
TI  - The Distribution and Immune Profile of T Cell Subsets in HIV-Infected Children
      from Uganda.
AB  - Abstract T cell activation is an important mechanism in HIV-associated immune
      depletion. We have previously demonstrated an association between the
      hyperactivation of CD4(+) and CD8(+) T cells and low CD4 status in HIV-infected
      Ugandan children. In this study, we explore differences in activation between
      naive and memory T cells in HIV-infected Ugandan children. A significant
      correlation between CD4- and CD8-mediated immune activation and CD4 status was
      observed only in the memory T cells. Antiretroviral (ART) untreated and treated
      HIV-positive and HIV-negative children displayed similar profiles of activation
      and distribution within the CD4(+) naive T cells. In contrast, significantly
      higher immune activation of the memory CD4(+) T cell subset was seen in ART
      untreated children when compared to ART-treated or HIV-negative children. ART
      mediated viral suppression led to the correction of CD4(+) immune activation to
      levels seen in uninfected children but did not increase the size of the memory
      CD4(+) T cell population. High levels of CD8(+) immune activation were also found
      in both naive and memory cell subsets. Antiretroviral treatment led to the
      normalization of CD8(+) T cell activation but did not correct the distribution of
      naive CD8(+) T cells. We also assessed PD-1 expression on CD8(+) T cells as a
      measure of immune dysfunction. Upregulation of PD-1 was highest in untreated
      children but persisted in ART-treated children compared to uninfected children.
      The mechanisms of immunopathogenesis in pediatric HIV infection likely involve
      distinct contributions from individual naive and memory T cells subsets.

PMID- 19182923
TI  - Cross-reactive T cell responses in HIV CRF01_AE and B'-infected intravenous drug
      users: implications for superinfection and vaccines.
AB  - Abstract We previously observed limited cross-reactive T cell responses in two
      HIV-1-superinfected injection drug users (IDUs) before superinfection [Ramos A,
      et al.: J Virol 2002;76(15):7444-7452]. To elucidate the role of such responses
      in superinfection we examined cross-reactive T cell responses in IDUs infected
      with a single HIV-1 subtype. In this study, IFN-gamma ELISPOT assays were
      performed using recombinant vaccinia constructs and peripheral blood mononuclear
      cells (PBMCs) from 43 IDUs singly infected with CRF01_AE or B' from the same
      cohort as the superinfected IDUs. PBMCs were from time points corresponding to
      pre- (early) or post- (late) superinfection in the superinfected IDUs. We
      observed that most singly infected IDUs had cross-reactivity in samples from
      early (84% of CRF01_AE and 78% of B'-infected IDUs) and late (96% of CRF_01AE and
      77% of B'-infected IDUs) time points. Frequent homologous reactivity at early
      (67% of CRF-01AE and 100% of B') and late (84% of CRF01_AE-infected and 100% of
      B'-infected IDUs) time points was also observed. Cross-reactive responses were
      predominantly to Pol and were broader and higher in CRF01_AE than in B'-infected
      IDUs (medians of 825 vs. 90 and 585 vs. 60 spot-forming units/10(6) PBMCs at
      early and late time points, respectively). Our results show that cross-reactive
      responses were more prevalent with greater height and breadth in singly infected
      IDUs than previously observed in corresponding collection time points of
      superinfected IDU. Thus, low or absent cross-reactivity may have contributed to
      the previously observed superinfections. These data are relevant for
      understanding superinfection and improving vaccine design.

PMID- 19182924
TI  - Molecular phylogenetics of nearly full-length HIV type 2 envelope gene sequences
      from West India.
AB  - Abstract While infection with HIV-1 has become a pandemic, the presence of HIV-2
      is also of concern in certain regions of the world. We have characterized the
      gp105 region of the envelope gene of HIV-2 isolates from Western India.
      Phylogenetic analysis of all 18 sequences revealed that these sequences were
      closely related to each other as well as to published African and European HIV-2
      group A sequences, with an overall genetic divergence of 10.9% (range 2-14%). Our
      study sequences showed close relatedness with West African HIV-2 group A (CAM
      group) sequences from Guinea Bissau with 89% homology. This was further confirmed
      by SimPlot as well as RIP analysis. Accordingly, the sequences presented here
      demonstrate the predominance of HIV-2 group A infection and show no evidence of
      HIV-2 recombination in Western India.

PMID- 19182925
TI  - Presence of HIV-1 CRF35_AD in Iran.

PMID- 19182926
TI  - A Simplified Formula for Inferring HIV Incidence from Cross-Sectional Surveys
      Using a Test for Recent Infection.

PMID- 19182927
TI  - Stereocontrol in N-directed hydroboration: synthesis of amino alcohols related to
      the piperidine alkaloids.
AB  - Treatment of 2-(2'-alkenyl)-piperidine boranes with iodine or triflic acid
      induces internal hydroboration with high regiocontrol, even with a terminal
      alkene (R = H). Good stereocontrol is possible for the N-benzyl substrates.
      Comparisons with acyclic model structures show that the source of regiocontrol
      with the terminal alkene is due to a steric effect of the axial piperidine C(3,5)
      hydrogens that destabilize the competing bridged bicyclic transition state.

PMID- 19182928
TI  - Synthesis of small glycopeptides by decarboxylative condensation and insight into
      the reaction mechanism.
AB  - The chemical synthesis of homogeneous glycoproteins and glycopeptides facilitates
      progress toward understanding the functional role of carbohydrates attached to
      proteins and is important in the preparation of glycopeptide-based therapeutics.
      A series of protected and unprotected glycosyl dipeptides, glycopeptide I, which
      contained the alpha-ketoacid moiety at the C-terminus, were synthesized and
      ligated with a series of O-tert-butyl-protected N-hydroxylamino acids to afford O
      tert-butyl-protected glycosyl tripeptides, glycopeptide II. The reactions were
      carried out under both anhydrous and aqueous conditions at neutral pH to produce
      glycopeptide products in yields ranging from 15% to 86% depending on the amino
      acids present at the ligation junction. The best yields were obtained when both
      the alpha-ketoacid and the N-hydroxylamino acid contained medium-sized side
      chains. In addition to the expected tripeptide product, 2,5-substituted oxazoles
      were isolated when O-tert-butyl protected N-hydroxylamines of glycine were
      employed in the reaction. The formation of the oxazole is believed to result from
      an intramolecular cyclization of the O-tert-butyl ester on a nitrilium ion
      intermediate followed by aromatization. A decarboxylative condensation between
      O(18)-labeled phenyl pyruvic acid and N-hydroxyphenethylamine oxalate salt
      resulted in amide products lacking the O(18)-label, providing further support for
      the nitrilium ion in the reaction pathway.

PMID- 19182929
TI  - Preparation and characterization of catechin sulfates, glucuronides, and
      methylethers with metabolic interest.
AB  - Catechins are major polyphenols in many plant foods that have been related to
      health promotion. In the human organism they are largely metabolized to different
      conjugates (sulfates, glucuronides, and methylethers), which are further found in
      plasma and would contribute to the biological effects associated with the intake
      of the parent compounds. Circulating metabolites are likely to possess biological
      properties different from those of the original compounds, and therefore, it is
      important to evaluate their activity, for which sufficient amounts of them are
      required that cannot be obtained by isolation from biological fluids. This paper
      describes the preparation of the methyl, sulfate, and glucuronide derivatives of
      catechins using different chemical syntheses and their characterization by HPLC
      DAD-ESI/MS. MS2 fragmentation of the compounds was also described that allowed
      the determination of the location of the different substituents on the catechin
      aglycones. The procedures optimized allowed the preparation of (epi)catechin
      sulfates, glucuronides, and methylethers conjugated at positions 3' and 4', as
      well as the sulfates at positions 5 and 7 with satisfactory yields for their
      further isolation by semipreparative-HPLC in view of their use in in vitro/ex
      vivo assays.

PMID- 19182931
TI  - Porous polymer adsorbent media constructed by molecular dynamics modeling and
      simulations: the immobilization of charged ligands and their effect on pore
      structure and local nonelectroneutrality.
AB  - A molecular dynamics modeling and simulation approach is presented and employed
      to construct porous dextran polymer ion-exchange adsorbent media. Both the
      activation step of the surface of the pores of the dextran polymer layer grafted
      on an agarose surface and the immobilization of charged ligands on the activated
      surface of the porous dextran polymer layer are considered. For the systems
      studied in this work, the activation step modifies slightly the pore structure of
      the base, nonactivated porous dextran polymer, while the immobilization of the
      ligands on the activated pore surface of the dextran layer changes significantly
      the pore structure of the activated dextran layer. The density distributions of
      the counterions and immobilized charged ligands along the direction of net
      transport in the adsorbent media constructed in this study are found to be
      nonuniform. The variables that affect the shape and magnitude of the density
      distributions of the counterions and immobilized charged ligands as well as the
      total number of charged ligands that can be immobilized on the activated porous
      dextran layer are identified and presented in this work. Furthermore, the data
      clearly show that there is local nonelectroneutrality in the porous dextran
      polymer ion-exchange adsorbent media, and this result has very important
      practical implications for the operation and performance of separation systems
      involving ion-exchange adsorbent media (e.g., ion-exchange chromatography
      systems). Also, the results of this work suggest approaches for (1) controlling
      the immobilization process of charged ligands and (2) constructing and studying
      the behavior of chromatographic polymeric monoliths and packed bed columns having
      a gradient of density of functionalities along the axis of the chromatographic
      polymeric monolith or packed bed column.

PMID- 19182939
TI  - Two-dimensional infrared spectroscopy provides evidence of an intermediate in the
      membrane-catalyzed assembly of diabetic amyloid.
AB  - Islet amyloid polypeptide (IAPP, also known as amylin) is responsible for
      pancreatic amyloid deposits in type 2 diabetes. The deposits, as well as
      intermediates in their assembly, are cytotoxic to pancreatic beta-cells and
      contribute to the loss of beta-cell mass associated with type 2 diabetes. The
      factors that trigger islet amyloid deposition in vivo are not well understood,
      but peptide membrane interactions have been postulated to play an important role
      in islet amyloid formation. To better understand the role of membrane
      interactions in amyloid formation, two-dimensional infrared (2D IR) spectroscopy
      was used to compare the kinetics of amyloid formation for human IAPP both in the
      presence and in the absence of negatively charged lipid vesicles. Comparison of
      spectral features and kinetic traces from the two sets of experiments provides
      evidence for the formation of an ordered intermediate during the membrane
      mediated assembly of IAPP amyloid. A characteristic transient spectral feature is
      detected during amyloid formation in the presence of vesicles that is not
      observed in the absence of vesicles. The spectral feature associated with the
      intermediate raises in intensity during the self-assembly process and
      subsequently decays in intensity in the classic manner of a kinetic intermediate.
      Studies with rat IAPP, a variant that is known to interact with membranes but
      does not form amyloid, confirm the presence of an intermediate. The analysis of
      2D IR spectra in terms of specific structural features is discussed. The unique
      combination of time and secondary structure resolution of 2D IR spectroscopy has
      enabled the time-evolution of a hIAPP intermediate to be directly monitored for
      the first time. The data presented here demonstrates the utility of 2D IR
      spectroscopy for studying membrane-catalyzed amyloid formation.

PMID- 19182940
TI  - Centrifugal sedimentation for selectively packing channels with silica microbeads
      in three-dimensional micro/nanofluidic devices.
AB  - Incorporation of nanofluidic elements into microfluidic channels is one approach
      for adding filtration and partition functionality to planar microfluidic devices,
      as well as providing enhanced biomolecular separations. Here we introduce a
      strategy to pack microfluidic channels with silica nanoparticles and microbeads,
      thereby indirectly producing functional nanostructures; the method allows
      selected channels to be packed, here demonstrated so that a separation channel is
      packed while keeping an injection channel unpacked. A nanocapillary array
      membrane is integrated between two patterned microfluidic channels that cross
      each other in vertically separated layers. The membrane serves both as a frit for
      bead packing and as a fluid communication conduit between microfluidic channels.
      Centrifugal force-assisted sedimentation is then used to selectively pack the
      microfluidic channels using an aqueous silica bead suspension loaded into the
      appropriate inlet reservoirs. This packing approach may be used to simultaneously
      pack multiple channels with silica microbeads having different sizes and surface
      properties. The chip design and packing method introduced here are suitable for
      packing silica particles in sizes ranging from nanometers to micrometers and
      allow rapid (approximately 10 min) packing with high quality. The liquid/analyte
      transport characteristics of these packed micro/nanofluidic devices have
      potential utility in a wide range of applications, including electroosmotic
      pumping, liquid chromatographic separations, and electrochromatography.

PMID- 19182941
TI  - Thromboxane A2 receptor antagonism by flavonoids: structure-activity
      relationships.
AB  - Thromboxane A2 (TxA2) is a strong platelet agonist involved in the pathogenesis
      of thrombotic diseases that elicits platelet aggregation and vasoconstriction
      through the activation of its specific membrane receptor (TP). Previous studies
      have demonstrated that certain flavonoids, naturally occurring phytochemicals,
      inhibit platelet function through several mechanisms, including antagonism of TP
      in these cells. However, the steric and inductive or mesomeric requirements
      underlying this effect are not fully understood. In this study, the ability of 20
      naturally occurring flavonoids belonging to different structural subtypes to
      inhibit [3H]-SQ29548 binding to platelet-rich plasma was compared to establish
      the structural basis explaining their TP antagonistic activity. The results show
      a key contribution of C7 and C8 carbons in the A ring, gamma-pyrone structure
      conjugated with a double bond between C2 and C3 carbons in the C ring, and C2',
      C3', and C4' carbons in the B ring as the structural determinants that create the
      active flavonoid skeleton in TP blockade. These data might help in the design of
      new TP antagonists with potential antithrombotic effects and provide additional
      evidence for the correlation between biological properties of flavonoids and
      their structure.

PMID- 19182942
TI  - Determination of the electron-detachment energies of 2'-deoxyguanosine 5'
      monophosphate anion: influence of the conformation.
AB  - The vertical electron-detachment energies (VDEs) of the singly charged 2'
      deoxyguanosine 5'-monophosphate anion (dGMP-) are determined by using the
      multiconfigurational second-order perturbation CASPT2 method at the MP2 ground
      state equilibrium geometry of relevant conformers. The origin of the unique low
      energy band in the gas phase photoelectron spectrum of dGMP-, with maximum at
      around 5.05 eV, is unambiguously assigned to electron detachment from the highest
      occupied molecular orbital of pi-character belonging to guanine fragment of a syn
      conformation. The presence of a short H-bond linking the 2-amino and phosphate
      groups, the guanine moiety acting as proton donor, is precisely responsible for
      the pronounced decrease of the computed VDE with respect to that obtained in
      other conformations. As a whole, the present research supports the nucleobase as
      the site with the lowest ionization potential in negatively charged
      (deprotonated) nucleotides at the most stable conformations as well as for B-DNA
      like type arrangements, in agreement with experimental evidence.

PMID- 19182943
TI  - Study of dexamethasone urinary excretion profile in cattle by LC-MS/MS:
      comparison between therapeutic and growth-promoting administration.
AB  - Dexamethasone is a potent synthetic corticosteroid widely employed as a
      therapeutic agent in cattle. Besides this legal use, corticosteroids are also
      administered at low dosages as growth-promoters either alone or in combination
      with other steroids or with beta-agonists. For this reason, appropriate control
      plans are established to survey corticosteroid misuse, using liver or urine as
      biological matrices. Since few data are available about the kinetics of
      dexamethasone excretion in meat cattle, an experimental study was designed to
      assess the drug residue levels in urines following either a therapeutic (60
      microg of dexamethasone sodium phosphate/kg b.w., for three consecutive days) or
      a growth-promoting schedule (0.7 or 1.4 mg of dexamethasone sodium phosphate per
      capita/day for 60 days). The urinary elimination of dexamethasone, which was
      predominantly excreted in the unmodified form, was determined by high-performance
      liquid chromatography/tandem mass spectrometry at different time intervals, i.e.
      during the treatments and after appropriate withdrawal times. Our findings
      confirm the high and rapid rate of dexamethasone urinary excretion irrespective
      of the nature of the treatment, and provide useful reference values that can be
      conveniently employed for forensic purposes.

PMID- 19182944
TI  - Differential analysis of mycoalexins in confrontation zones of grapevine fungal
      pathogens by ultrahigh pressure liquid chromatography/time-of-flight mass
      spectrometry and capillary nuclear magnetic resonance.
AB  - An original approach was developed for the chemical and biological investigation
      of zone lines formed by the confrontation of fungi growing in confined spaces.
      Two wood-decaying fungi involved in esca disease, Eutypa lata and Botryosphaeria
      obtusa, were grown in Petri dishes. Metabolic profiles of pure fungal strains and
      confrontation zones were differentially analyzed by ultrahigh pressure liquid
      chromatography coupled to time-of-flight mass spectrometry (UHPLC/TOFMS).
      Selected metabolites induced by the confrontation were isolated and characterized
      by capillary NMR (CapNMR) at the submilligram level. Fungitoxic and phytotoxic
      assays were applied to the crude extracts and isolated molecules. While the
      extracts of pure strains were inactive, the extract from confrontation zones
      exhibited significant activities. A very strongly induced compound, O
      methylmellein, may explain these toxic properties. The developed approach
      demonstrates the use of fungal confrontations as an original source of bioactive
      molecules and gives new insights into the study of esca disease.

PMID- 19182945
TI  - Determination of the Forster distance in polymer films by fluorescence decay for
      donor dyes with a nonexponential decay profile.
AB  - Fluorescence resonance energy transfer (FRET) experiments were carried out on
      three pairs of donor-acceptor dyes in polymer films in which the donor dyes had
      absorption maxima in the range of 350-450 nm. Two of the donors, a coumarin dye
      and a naphthalimide dye covalently bound to polystyrene, gave nonexponential
      decays in the absence of acceptors. The decay profiles could be fitted to a
      stretched exponential form with a beta value on the order of 0.9. We developed
      equations for analyzing donor fluorescence intensity decay profiles for donor
      acceptor mixtures in rigid matrices for the case of donors showing relatively
      small deviations from exponentiality. To test these equations, we calculate
      values of the Forster radius (R0(FR)) from the decay profile data and compare
      these values to the Forster radius R0(SO) determined by the traditional spectral
      overlap method. Agreement between these values validates the methodology
      developed here for the use of such donor dyes in FRET studies of more complex
      polymer systems.

PMID- 19182948
TI  - Antioxidant assays for plant and food components.
AB  - Recently, research on natural antioxidants has become increasingly active in
      various fields. Accordingly, numerous articles on natural antioxidants, including
      polyphenols, flavonoids, vitamins, and volatile chemicals, have been published.
      Assays developed to evaluate the antioxidant activity of plants and food
      constituents vary. Therefore, to investigate the antioxidant activity of
      chemical(s), choosing an adequate assay based on the chemical(s) of interest is
      critical. There are two general types of assays widely used for different
      antioxidant studies. One is an assay associated with lipid peroxidations,
      including the thiobarbituric acid assay (TBA), malonaldehyde/high-performance
      liquid chromatography (MA/HPLC) assay, malonaldehyde/gas chromatography (MA/GC)
      assay, beta-carotene bleaching assay, and conjugated diene assay. Other assays
      are associated with electron or radical scavenging, including the 2,2-diphenyl-1
      picrylhydrazyl (DPPH) assay, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic
      acid) (ABTS) assay, ferric reducing/antioxidant power (FRAP) assay, ferrous
      oxidation-xylenol orange (FOX) assay, ferric thiocyanate (FTC) assay, and
      aldehyde/carboxylic acid (ACA) assay. In this review, assays used recently were
      selected for extended discussion, including discussion of the mechanisms
      underlying each assay and its application to various plants and foods.

PMID- 19182949
TI  - Calvatia lilacina protein-extract induces apoptosis through glutathione depletion
      in human colorectal carcinoma cells.
AB  - This paper reports that a novel protein extract isolated from Calvatia lilacina
      (CL) can induce cell death against four types of human colorectal cancer cells.
      Importantly, CL was shown to be free of apoptotic effects against normal rat
      liver cells. We have also identified that CL-induced glutathione (GSH) depletion
      is the major contributor responsible for the apoptotic cell death induction of SW
      480 cells, as evidenced by the observation that exogenously added N
      acetylcysteine (NAC), or GSH, but not vitamin C, could offer a near complete
      protection of CL-treated cells against apoptotic cell death. Furthermore, the
      participation of reactive oxygen species (ROS) evoked a drop in the transmembrane
      potential (Delta Psi(m)) in the CL-induced apoptotic cell death. This observation
      can only be deemed as a minor pathway due to the fact that cyclosporine A (CyA)
      could only partially rescue the CL-treated cells from apoptotic cell death.
      Likewise, despite the fact that CL could induce the upregulation of Bax, its
      knockdown via siRNA (48 h) failed to completely mitigate apoptotic cell death,
      indicating that its role in this apoptotic process was insignificant. To further
      explore the possible underlying mechanism associated with CL-induced GSH
      depletion, we proceeded to determine the effect of CL on the cellular gamma
      glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme responsible for
      GSH biosynthesis, and demonstrated that indeed gamma-GCS could be repressed by
      CL. Taken together, we report here for the first time that the anticancer effect
      of CL on human colorectal cancer cells is mediated through GSH depletion
      mechanism rather than a ROS-mediated killing process. This functional attribute
      of CL can thus provide the basis for the strategic design of a treatment of
      colorectal cancer.

PMID- 19182950
TI  - Compound K, intestinal metabolite of ginsenoside, attenuates hepatic lipid
      accumulation via AMPK activation in human hepatoma cells.
AB  - Compound K (CK) is a major intestinal metabolite of ginsenosides derived from
      ginseng radix. Although antidiabetic and antihyperlipidemic activities of CK have
      been investigated in recent years, action mechanism of CK remains poorly
      understood. Therefore, we examined whether CK affects the lipid metabolism in
      insulin-resistant HepG2 human hepatoma cells. In this study, a significant
      increase in AMP-activated protein kinase (AMPK) was observed when the cells were
      treated with CK. Activation of AMPK was also demonstrated by measuring the
      phosphorylation of acetyl-CoA carboxylase (ACC), a substrate of AMPK. CK
      attenuated gene expression of sterol regulatory element-binding protein 1c
      (SREBP1c) in time- and dose-dependent manners. Genes for fatty acid synthase
      (FAS) and stearoyl-CoA desaturase 1 (SCD1), well-known target molecules of
      SREBP1c, were also suppressed. In contrast, gene expressions of peroxisome
      proliferator-activated receptor alpha (PPAR-alpha) and CD36 were increased. These
      effects were reversed by treatment of compound C, an AMPK inhibitor. However,
      there were no differences in gene expressions of SREBP2, hydroxymethyl glutaryl
      CoA reductase (HMGR), and low-density-lipoprotein receptor (LDLR). Taken
      together, AMPK mediates CK induced suppression and activation of SREBP1c and PPAR
      alpha, respectively, and these effects seem to be one of antidiabetic and/or
      antihyperlipidemic mechanisms of CK in insulin-resistant HepG2 human hepatoma
      cells.

PMID- 19182951
TI  - Interaction between salt-free catanionic TTAOH-LA mixtures and nonionic polymers:
      surface tension and rheological study.
AB  - By mixing tetradecyltrimethylammonium hydroxide (TTAOH) and lauric acid (LA) in
      water, the salt-free cationic/anionic (catanionic) surfactant system TTAOH/LA/H2O
      can be constructed. Based on our recent presentation of the TTAOH/LA/H2O ternary
      phase diagram, we investigate the interaction between TTAOH-LA mixtures and two
      kinds of nonionic polymers, Pluronic F127 (PEO-PPO-PEO triblock copolymer,
      EO(97)PO(69)EO(97)) and polyvinylpyrrolidone (PVP), by means of surface tension
      and rheological measurements. It is found that the presence of F127 has an
      obvious influence on the surface activity of the TTAOH/LA/H2O system in the TTAOH
      rich side. Upon addition of F127, a smaller critical micellar concentration (cmc)
      and a higher surface tension after cmc (gamma(cmc)) were observed, which should
      be due to the complex formation between F127 and TTAOH-LA mixtures at the
      air/water interface. F127 is also found to associate strongly with TTAOH-LA
      mixtures in bulk aqueous solutions, as revealed by rheological measurements. The
      association leads to a significant decrease in micelle length and makes the
      vesicular phase more fluid. The influence of PVP on the surface activity and
      rheological properties of the TTAOH/LA/H2O system, however, is much less obvious
      compared with that of F127. In the TTAOH-rich side, only a very limited effect
      has been observed, indicating a rather weak association between PVP and
      surfactants. As the LA content increases, the influence of PVP on rheological
      properties of the TTAOH/LA/H2O system becomes detectable in the wormlike micellar
      region and vesicular region. However, the influence of PVP remains weaker
      compared with that of F127.

PMID- 19182952
TI  - The alkaloid profiles of Lupinus sulphureus.
AB  - Lupines are common plants on the rangelands in the western United States. Lupines
      contain alkaloids that can be toxic and teratogenic causing congenital birth
      defects (crooked calf disease). One such lupine, Lupinus sulphureus, occurs in
      parts of Oregon, Washington, and British Columbia. Specimens of L. sulphureus
      from field collections and herbaria were evaluated taxonomically and by chemical
      means. A total of seven distinct alkaloid profiles and the individual alkaloids
      associated with each profile were identified. Each alkaloid profile was unique in
      its geographical distribution and its potential risk to livestock. In conclusion,
      taxonomic classification is not sufficient to determine risk, as chemical
      characterization of the alkaloids must also be performed.

PMID- 19182954
TI  - Structural and kinetic studies on native intermediates and an intermediate
      analogue in benzoylformate decarboxylase reveal a least motion mechanism with an
      unprecedented short-lived predecarboxylation intermediate.
AB  - The thiamin diphosphate- (ThDP-) dependent enzyme benzoylformate decarboxylase
      (BFDC) catalyzes the nonoxidative decarboxylation of benzoylformic acid to
      benzaldehyde and carbon dioxide. To date, no structural information for a
      cofactor-bound reaction intermediate in BFDC is available. For kinetic analysis,
      a chromophoric substrate analogue was employed that produces various absorbing
      intermediates during turnover but is a poor substrate with a 10(4)-fold
      compromised kcat. Here, we have analyzed the steady-state distribution of native
      intermediates by a combined chemical quench/1H NMR spectroscopic approach and
      estimated the net rate constants of elementary catalytic steps. At substrate
      saturation, carbonyl addition of the substrate to the cofactor (k' approximately
      500 s-1 at 30 degrees C) and elimination of benzaldehyde (k' approximately 2.400
      s-1) were found to be partially rate-determining for catalysis, whereas
      decarboxylation of the transient 2-mandelyl-ThDP intermediate is 1 order of
      magnitude faster with k' approximately 16.000 s-1, the largest rate constant of
      decarboxylation in any thiamin enzyme characterized so far. The X-ray structure
      of a predecarboxylation intermediate analogue was determined to 1.6 A after
      cocrystallization of BFDC from Pseudomonas putida with benzoylphosphonic acid
      methyl ester. In contrast to the free acid, for which irreversible
      phosphorylation of active center Ser26 was reported, the methyl ester forms a
      covalent adduct with ThDP with a similar configuration at C2alpha as observed for
      other thiamin enzymes. The C2-C2alpha bond of the intermediate analogue is out of
      plane by 7degrees, indicating strain. The phosphonate part of the adduct forms
      hydrogen bonds with Ser26 and His281, and the 1-OH group is held in place by
      interactions with His70 and the 4'-amino group of ThDP. The phenyl ring
      accommodates in a hydrophobic pocket formed by Phe464, Phe397, Leu109, and
      Leu403. A comparison with the previously determined structure of BFDC in
      noncovalent complex with the inhibitor (R)-mandelate suggests a least motion
      mechanism. Binding of benzoylphosphonic acid methyl ester to BFDC was further
      characterized by CD spectroscopy and stopped-flow kinetics, indicating a two-step
      binding mechanism with a 200-fold slower carbonyl addition to ThDP than
      determined for benzoylformic acid, in line with the observed slight structural
      reorganization of Phe464 due to steric clashes with the phosphonate moiety.

PMID- 19182963
TI  - Photodissociation of isolated ferric heme and heme-His cations in an
      electrostatic ion storage ring.
AB  - Photodissociation of isolated Fe(III)-heme(+) and Fe(III)-heme(+)(His) ions in
      the gas phase has been investigated using an electrostatic storage ring. The
      experiment provides three pieces of information, namely fragmentation channels,
      dissociation times, and absorption spectra. After photoexcitation with either 390
      or 532 nm light, we find that the fragmentation takes place on a microsecond to
      millisecond time scale, and the channels are CH(2)COOH loss (beta-cleavage
      reaction) and histidine loss from Fe(III)-heme(+) and Fe(III)-heme(+)(His),
      respectively. These channels were also observed by means of collision-induced
      dissociation. Significant information on the nonradiative processes that occur
      after photoexcitation was revealed from the decay spectra. At early times (first
      two to three milliseconds), the decay of the photoexcited ions is well-described
      by a statistical model based on an Arrhenius-type expression for the rate
      constant. The activation energy and preexponential factor are 1.9 +/- 0.2 eV and
      1 x 10(17) to 1 x 10(21) s(-1) for heme(+) and 1.4 +/- 0.2 eV and 1 x 10(16) to 1
      x 10(19) s(-1) for heme(+)(His). Decay on a longer time scale was also observed
      and is ascribed to the population of lower-lying states with higher spin
      multiplicity because intersystem crossing back to the electronic ground-state is
      a bottleneck for the dissociation. The measurements give lifetimes for these
      lower-lying states of about 10 ms after 390 nm excitation and we estimate the
      probability of spin flip to be 0.3 and 0.8 for heme(+) and heme(+)(His),
      respectively.

PMID- 19182964
TI  - Foodborne disease trends and reports.

PMID- 19182965
TI  - Isothiocyanate profile and selective antibacterial activity of root, stem, and
      leaf extracts derived from Raphanus sativus L.
AB  - Acetone and hexane extracts derived from the root, stem, and leaf of Raphanus
      sativus were investigated for their antibacterial activity against foodborne and
      resistant pathogens, such as Bacillus subtilis, Staphylococcus aureus,
      Staphylococcus epidermidis, Enterococcus faecalis, Salmonella typhimurium,
      Enterobacter aerogenes, Enterobacter cloacae, and Escherichia coli. Total and
      individual isothiocyanate (ITC) components and their relationship with the
      antibacterial activity of R. sativus were also evaluated. Both acetone and hexane
      fractions of root, stem, and leaf exhibited selective antibacterial activity
      against the organisms tested. Antibacterial activity was strongest in the acetone
      fraction of root with larger zone of inhibition and lower minimum inhibitory
      concentration. The results obtained were comparable to that seen with standard
      antibiotics. Of the different parts of R. sativus studied, root tended to be more
      active than the stem and leaf extracts in inhibiting the bacterial growth. Gas
      chromatographic analysis revealed the presence of variable amounts of five
      different ITCs such as allyl isothiocyanate (AITC), phenyl isothiocyanate (PITC),
      benzyl isothiocyanate (BITC), phenethyl isothiocyanate, and 4-(methylthio)-3
      butenyl isothiocyanate (MTBITC) in different parts of the plant. The low linear
      correlation between the total ITC content and antibacterial activity implied that
      bacterial growth inhibitory ability of R. sativus was not dependent on the total
      ITC content. However, the antibacterial activity of R. sativus was well
      correlated with AITC, PITC, and BITC for all organisms except for Enteroc.
      faecalis, whose inhibitory effect was more related to MTBITC.

PMID- 19182967
TI  - Effects of bending and bending angular momentum on reaction of NO2+ with C2H2: a
      quasi-classical trajectory study.
AB  - A large set of quasi-classical trajectories were calculated at the PBE1PBE/6
      311G** level of theory, in an attempt to understand the mechanistic origins of
      the large, mode-specific enhancement of the O-transfer reaction by NO2+ bending
      vibration and the surprisingly large suppressing effect of bending angular
      momentum. The trajectories reproduce the magnitude of the absolute reaction cross
      section, and also get the dependence of reactivity on NO2+ vibrational state, and
      the vibrational state dependent scattering behavior qualitatively correct.
      Analysis of the trajectories shows that the bending effect is not simply a
      consequence of enhanced reactivity in bent geometries but, rather, that
      excitation of bending motion allows reaction in a wider range of orientation
      angles, even if the NO2+ is not bent at the onset of the collisional interaction.
      There is a strong interplay between NO2+ bending and transient charge transfer
      during the collisions. Such charge transfer enhances reactivity, but only if the
      reactants are oriented correctly.

PMID- 19182966
TI  - Intramolecular dynamics of RS-SR' systems (R, R' = H, F, Cl, CH3, C2 H5):
      torsional potentials, energy levels, partition functions.
AB  - The equilibrium and cis and trans geometric structures of a series of disulfides
      RS-SR' (HSSH, HSSF, HSSCl, HSSCH3, HSSC2H5, FSSF, ClSSCl, ClSSF, CH3SSCH3,
      C2H5SSC2H5) have been studied using both density functional theory (B3LYP/6
      311++G(3df, 3pd)) and second-order Moller-Plesset perturbation theory
      (MP2(FU)/aug-cc-pVTZ). The effects of internal rotation on the structural
      parameters have been analyzed and the torsional potentials around the S-S bond
      have been compared with experimental and theoretical information, when available,
      as well as with the analogues of the peroxydic family. Torsional levels were
      calculated, and their distribution as a function of temperature was determined,
      obtaining partition functions. This information is of interest for statistical
      approaches to equilibrium properties and to rates of processes in which torsional
      anharmonicity is relevant. It is also required for recent atmospheric modeling
      studies and also for prototypical chiral separation experiments, in view of a
      possible dynamic mechanism for chirality exchange by molecular collisions. In
      general, barriers for such processes are higher than for the corresponding
      peroxides, and accordingly, rates for chirality change are estimated to be
      consistently smaller.

PMID- 19182968
TI  - Dynamics of CO2 scattering off a perfluorinated self-assembled monolayer.
      Influence of the incident collision energy, mass effects, and use of different
      surface models.
AB  - The dynamics of collisions of CO2 with a perfluorinated alkanethiol self
      assembled monolayer (F-SAM) on gold were investigated by classical trajectory
      calculations using explicit atom (EA) and united atom (UA) models to represent
      the F-SAM surface. The CO2 molecule was directed perpendicularly to the surface
      at initial collision energies of 1.6, 4.7, 7.7, and 10.6 kcal/mol. Rotational
      distributions of the scattered CO2 molecules are in agreement with experimental
      distributions determined for collisions of CO2 with liquid surfaces of
      perfluoropolyether. The agreement is especially good for the EA model. The role
      of the mass in the efficiency of the energy transfer was investigated in separate
      simulations in which the mass of the F atoms was replaced by either that of
      hydrogen or chlorine, while keeping the potential energy function unchanged. The
      calculations predict the observed trend that less energy is transferred to the
      surface as the mass of the alkyl chains increases. Significant discrepancies were
      found between results obtained with the EA and UA models. The UA surface leads to
      an enhancement of the energy transfer efficiency in comparison with the EA
      surface. The reason for this is in the softer structure of the UA surface, which
      facilitates transfer from translation to interchain vibrational modes.

PMID- 19182969
TI  - An ab initio theoretical study of the electronic structure of UO2(+) and
      [UO2(CO3)3]5-.
AB  - The electronic spectra up to 50,000 cm(-1) of uranyl(V) both as a bare ion,
      UO2(+), and coordinated with three carbonate ligands, [UO2(CO3)3]5-, are
      presented. Solvent effects were treated by a nonequilibrium continuum solvent
      model. The transition energies were obtained at the spin-orbit level using
      relativistic wave function based multiconfigurational methods such as the
      complete active space self-consistent field method (CASSCF)and the complete
      active space with second-order perturbation theory (CASPT2) followed by a
      calculation of the spin-orbit effects at the variation-perturbation level.
      Earlier relativistic intermediate Hamiltonian Fock space coupled-cluster
      calculations on the spectrum of the bare uranyl(V) ion were extended to
      investigate the influence of electron correlation effects on spacings between the
      electronic states. This study is an attempt to contribute to an enhanced
      understanding of the electronic structure of actinyl ions. Both spectra show
      transitions within nonbonding orbitals and between nonbonding and antibonding
      orbitals as well as charge transfers from the uranyl oxygens to uranium. The
      ground state in UO2(+) is found to be 2Phi(5/2u), corresponding to the
      sigma(u)(2)phi(u)(1) configuration, while in [UO2(CO3)3]5-, it is 2Delta(3/2u),
      arising from the sigma(u)(2)delta(u)(1) configuration. It is remarkable that the
      excited state corresponding to an excitation from the nonbonding delta(u) to the
      uranyl antibonding 3pi(u)* molecular orbital is significantly lower in energy in
      the carbonate complex, 6623 cm(-1), than that in the bare ion, 17,908 cm(-1). The
      first ligand (carbonate) to metal charge-transfer excitation is estimated to
      occur above 50,000 cm(-1). The reported results compare favorably with experiment
      when available.

PMID- 19182970
TI  - Analysis of kinetic isotope effects for proton-coupled electron transfer
      reactions.
AB  - A series of rate constant expressions for nonadiabatic proton-coupled electron
      transfer (PCET) reactions are analyzed and compared. The approximations
      underlying each expression are enumerated, and the regimes of validity for each
      expression are illustrated by calculations on model systems. In addition, the
      kinetic isotope effects (KIEs) for a series of model PCET reactions are analyzed
      to elucidate the fundamental physical principles dictating the magnitude of the
      KIE and the dependence of the KIE on the physical properties of the system,
      including temperature, reorganization energy, driving force, equilibrium proton
      donor-acceptor distance, and effective frequency of the proton donor-acceptor
      mode. These calculations lead to three physical insights that are directly
      relevant to experimental data. First, these calculations provide an explanation
      for a decrease in the KIE as the proton donor-acceptor distance increases, even
      though typically the KIE will increase with increasing equilibrium proton donor
      acceptor distance if all other parameters remain fixed. Often the proton donor
      acceptor frequency decreases as the proton donor-acceptor distance increases, and
      these two effects impact the KIE in opposite directions, so either trend could be
      observed. Second, these calculations provide an explanation for an increase in
      the KIE as the temperature increases, even though typically the KIE will decrease
      with increasing temperature if all other parameters remain fixed. The combination
      of a rigid hydrogen bond, which corresponds to a high proton donor-acceptor
      frequency, and low solvent polarity, which corresponds to small solvent
      reorganization energy, allows the KIE to either increase or decrease with
      temperature, depending on the other properties of the system. Third, these
      calculations provide insight into the dependence of the rate constant and KIE on
      the driving force, which has been studied experimentally for a wide range of PCET
      systems. The rate constant increases as the driving force becomes more negative
      because excited vibronic product states associated with low free energy barriers
      and relatively large vibronic couplings become accessible. The ln[KIE] has a
      maximum near zero driving force and decreases significantly as the driving force
      becomes more positive or negative because the contributions from excited vibronic
      states increase as the reaction becomes more asymmetric, and contributions from
      excited vibronic states decrease the KIE. These calculations and analyses lead to
      experimentally testable predictions of trends in the KIEs for PCET systems.

PMID- 19182971
TI  - QM/MM study of thymidylate synthase: enzymatic motions and the temperature
      dependence of the rate limiting step.
AB  - Thymidylate synthase (TS) is an enzyme that catalyzes a complex cascade of
      reactions. A theoretical study of the reduction of an exocyclic methylene
      intermediate by hydride transfer from the 6S position of 5,6,7,8-tetrahydrofolate
      (H(4)folate), to form 2'-deoxyuridine 5'-monophosphate (dTMP) and 7,8
      dihydrofolate (H(2)folate), has been carried out using hybrid quantum
      mechanics/molecular mechanics methods. This step is of special interest because
      it is the rate-limiting step of the reaction catalyzed by TS. The acceptor of
      this hydride is an intermediate that is covalently bound to the enzyme via a
      thioether bond to an overall conserved active site cysteine residue (Cys146 in
      Escherichia coli). Heretofore, whether the hydride transfer precedes the thiol
      abstraction that releases the product from the enzyme or whether these two
      processes are concerted has been an open question. We have examined this step in
      terms of free energy surfaces obtained at the same temperatures we previously
      used in experimental studies of this mechanistic step (273-313 K). Analysis of
      the results reveals that substantial features of the reaction and the nature of
      the H-transfer seem to be temperature independent, in agreement with our
      experimental data. The findings also indicate that the hydride transfer and the
      scission of Cys146 take place in a concerted but asynchronous fashion. This 1,3
      S(N)2 substitution is assisted by arginine 166 and several other arginine
      residues in the active site that polarize the carbon-sulfur bond and stabilize
      the charge transferred from cofactor to substrate. Finally, the simulation
      elucidates the molecular details of the enzyme's motion that brings the system to
      its transition state and, in accordance with the experimental data, indicates
      that this "tunneling ready" conformation is temperature independent.

PMID- 19182973
TI  - Light and life: a personal overview of development in the fields of photosurgery
      and phototherapy.

PMID- 19182972
TI  - Clinical evaluation of lasers and sodium fluoride gel in the treatment of dentine
      hypersensitivity.
AB  - OBJECTIVE: The aim of the present study was to evaluate and compare the efficacy
      of CO(2) and Er:YAG lasers alone and in combination with topical sodium fluoride
      (NaF) in the management of dentine hypersensitivity. MATERIALS AND METHODS: A
      group of 50 patients presenting with a total of 420 hypersensitive teeth were
      randomly allocated into five groups. Group 1 was treated with 2% NaF, groups 2
      and 3 were lased by a CO(2) (1 W, continuous wave mode, for 10 sec) or Er:YAG (30
      Hz, 60 mJ for 10 sec, without water/air spray) laser, and groups 4 and 5 received
      NaF plus the CO(2) and the Er:YAG laser, respectively. The scanning speed of the
      laser was 0.8 mm/sec. The degree of thermal sensitivity was determined with an
      evaporative stimulus consisting of a 1-sec air blast at a distance of 2 mm from
      each site tested. Quantification of the degree of discomfort was determined
      according to a four-point pain scale before treatment and 1 wk, 1 mo, and 6 mo
      after treatment. RESULTS: All treatment forms resulted in significant improvement
      of discomfort. At 1 wk, 1 mo, and 6 mo, cold air blast scores were significantly
      reduced compared to baseline scores, except for the NaF group. In the NaF group,
      there was a statistically significant increase in mean degree of discomfort at 6
      mo compared with 1 wk (p +/- 0.01) and 1 mo (p +/- 0.001). Comparison of the
      other treatment regimens revealed that cold air blast scores were significantly
      lower for the other four treatments than for NaF gel alone (p +/- 0.001). No
      superiority was found for desensitization among the CO(2), Er:YAG, CO(2) + NaF,
      and Er:YAG + NaF groups. CONCLUSIONS: We concluded that both the CO(2) and Er:YAG
      lasers have promising potential for the treatment of dentine hypersensitivity.
      Lasers in combination with NaF gel appear to show better efficacy compared to
      either treatment modality alone.

PMID- 19182974
TI  - The efficacy of laser fluorescence to detect in vitro demineralization and
      remineralization of smooth enamel surfaces.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of the laser
      fluorescence (LF) device in detecting in vitro demineralization and
      remineralization of smooth surface caries-like lesions. BACKGROUND DATA: The
      early detection of smooth surface caries-like lesions is important to provide
      proper management of carious lesions, and allows monitoring of them over time.
      Also, some authors suggest that LF could be useful in monitoring the caries
      pathological process. MATERIALS AND METHODS: Seventy-eight blocks of bovine teeth
      were obtained, and then submitted to artificial caries lesion induction and to a
      pH-cycling process. Superficial microhardness (SMH) and laser fluorescence
      analysis were performed at baseline, after induction of caries-like lesions, and
      after the pH-cycling regimen to promote remineralization. RESULTS: Friedman's and
      multiple comparison tests were performed for all variables. SMH analysis showed
      significant differences (p +/- 0.05) between baseline (286.77 +/- 1.49 Vickers
      hardness number [VHN] units), before (38.48 +/- 0.85 VHN), and after
      remineralization (131.93 +/- 2.63 VHN). Baseline values for LF were extremely low
      (2.71 +/- 0.05), and a statistically significant difference was observed only
      after remineralization (3.61 +/- 0.08), as demonstrated by the increase in LF
      values. CONCLUSION: The LF device did not show efficacy for monitoring in vitro
      demineralization and remineralization of smooth enamel surfaces.

PMID- 19182976
TI  - Effect of laser phototherapy on the release of TNF-alpha and MMP-1 by endodontic
      sealer-stimulated macrophages.
AB  - OBJECTIVE: Our aim was to analyze the effect of laser phototherapy on the
      secretory activity of macrophages activated by interferon-gamma (IFN-gamma) and
      lipopolysaccharide (LPS), and stimulated by substances leached from an epoxy
      resin-based sealer (AH-Plus) and a calcium hydroxide-based sealer (Sealapex).
      BACKGROUND DATA: Laser phototherapy can modulate the inflammatory process,
      improving wound healing. This type of therapy could be useful for modulating
      postoperative symptoms seen after endodontic treatment. MATERIALS AND METHODS:
      Cytotoxicity was indirectly assessed by measuring mitochondrial activity.
      Macrophages were stimulated by the leached substances or not (controls), and the
      groups were then irradiated or not. The secretion of pro-inflammatory cytokines
      (TNF-alpha and MMP-1) was analyzed using ELISA. Two irradiations at 6-h intervals
      were done with an As-Ga-Al diode laser (780 nm, 70 mW, spot size 4.0 mm(2), 3
      J/cm(2), for 1.5 sec) in contact mode. RESULTS: The sealers were non-cytotoxic to
      macrophages. The production of TNF-alpha was significantly decreased by laser
      phototherapy, regardless of experimental group. The level of secretion of MMP-1
      was similar in all groups. CONCLUSION: Based on the conditions of this study we
      concluded that in activated macrophages, laser phototherapy impairs the secretion
      of the pro-inflammatory cytokine TNF-alpha, but has no influence on MMP-1
      secretion.

PMID- 19182977
TI  - Angiogenesis in calcium phosphate scaffolds by inorganic copper ion release.
AB  - Angiogenesis in a tissue-engineered device may be induced by incorporating growth
      factors (e.g., vascular endothelial growth factor [VEGF]), genetically modified
      cells, and=or vascular cells. It represents an important process during the
      formation and repair of tissue and is essential for nourishment and supply of
      reparative and immunological cells. Inorganic angiogenic factors, such as copper
      ions, are therefore of interest in the fields of regenerative medicine and tissue
      engineering due to their low cost, higher stability, and potentially greater
      safety compared with recombinant proteins or genetic engineering approaches. The
      purpose of this study was to compare tissue responses to 3D printed macroporous
      bioceramic scaffolds implanted in mice that had been loaded with either VEGF or
      copper sulfate. These factors were spatially localized at the end of a single
      macropore some 7 mm from the surface of the scaffold. Controls without angiogenic
      factors exhibited only poor tissue growth within the blocks; in contrast, low
      doses of copper sulfate led to the formation of microvessels oriented along the
      macropore axis. Further, wound tissue ingrowth was particularly sensitive to the
      quantity of copper sulfate and was enhanced at specific concentrations or in
      combination with VEGF. The potential to accelerate and guide angiogenesis and
      wound healing by copper ion release without the expense of inductive protein(s)
      is highly attractive in the area of tissue-engineered bone and offers significant
      future potential in the field of regenerative biomaterials.

PMID- 19182978
TI  - A two-stage feature selection method for gene expression data.
AB  - Microarray data referencing gene expression profiles provide valuable answers to
      a variety of problems, and contributes to advances in clinical medicine. Gene
      expression data typically has a high dimension and a small sample size.
      Generally, only relatively small numbers of gene expression data are strongly
      correlated with a certain phenotype. To analyze gene expression profiles
      correctly, feature (gene) selection is crucial for classification. Feature (gene)
      selection has certain advantages, such as effective extraction of genes that
      influence classification accuracy, elimination of irrelevant genes, and
      improvement of the classification accuracy calculation. In this paper, we propose
      a two-stage feature selection method, which uses information gain to implement a
      gene-ranking process, and combines an improved particle swarm optimization with
      the K-nearest neighbor method and support vector machine classifiers to calculate
      the classification accuracy. The experimental results show that the proposed
      method can effectively select relevant gene subsets, and achieves higher
      classification accuracy than previous studies.

PMID- 19182980
TI  - Support needs of overweight African American women for weight loss.
AB  - OBJECTIVES: To examine social support needs of obese and overweight African
      American women for weight loss. METHODS: Focus groups were conducted with
      overweight and obese African American women. Data were analyzed using standard
      grounded theory text analysis. RESULTS: Our middle-aged (45.7 years; SD = 12.6)
      women (N = 66) were interested in receiving support from others focused on the
      health benefits of weight loss. Behaviors perceived as supportive include co
      participating in exercise, providing nutrition education, using positive
      reinforcements, and avoiding criticism. CONCLUSIONS: African American women are
      interested in a program designed to increase social support for their weight
      loss.

PMID- 19182981
TI  - Perceived neighborhood fear and drug use among young adults.
AB  - OBJECTIVES: To examine the association between perceptions of neighborhood safety
      and drug use, as well as mediation by depression and self-esteem. METHODS: The
      sample included 210 inner-city young adults (18 to 25 years) recruited from the
      Atlanta, Georgia, USA. RESULTS: Respondents who indicated greater fear of their
      neighborhood environment also had significantly greater levels of drug use than
      did those with lower perceived fear. However, this relationship was not a result
      of lower self-esteem or higher levels of depressive symptoms. CONCLUSIONS:
      Exploratory results point to the need to consider the broader role of the
      community environment and its impact on drug use among young adults.

PMID- 19182982
TI  - Smoking beliefs and behavior among youth in Malaysia and Thailand.
AB  - OBJECTIVE: To characterize smoking beliefs among Thai and Malaysian youth and to
      examine associations with gender, antismoking media exposure, and smoking status.
      METHODS: Nationally representative samples of youth completed self-administered
      questionnaires. RESULTS: A substantial proportion of youth reported positive
      beliefs about smoking. Those reporting positive beliefs were more likely to be
      susceptible to smoking. Youth who noticed antismoking media were less likely to
      report positive beliefs about smoking. CONCLUSIONS: As in Western countries,
      beliefs about smoking held by youth in Southeast Asia are associated with smoking
      status. Antismoking media may be an important means of targeting beliefs about
      smoking among youth.

PMID- 19182983
TI  - Lay management of chronic disease: a qualitative study of living with hepatitis C
      infection.
AB  - OBJECTIVES: To examine management strategies and goals reported by people
      diagnosed with chronic hepatitis C. METHODS: We analyzed data from semistructured
      interviews (N = 42) and from electronic sources [illness narratives (N = 79) and
      Internet threaded discussions (N = 264)]. Line-by-line coding, comparisons, and
      team discussions generated catalogs of lay management strategies and goals. We
      analyzed code-based files to identify informants' selection of specific
      strategies for each goal. RESULTS: We classified lay management strategies into 3
      categories: medical self-care, behavior change, and coping. These strategies were
      used selectively in addressing multiple goals, categorized as fighting the virus,
      strengthening the body, and managing consequences. CONCLUSIONS: Results
      underscore the diversity of strategies for living with a disease characterized by
      uncertain prognosis and variable expression of symptoms.

PMID- 19182984
TI  - College student invulnerability beliefs and HIV vaccine acceptability.
AB  - OBJECTIVE: To examine behavioral history, beliefs, and vaccine characteristics as
      predictors of HIV vaccine acceptability. METHODS: Two hundred forty-five US
      undergraduates were surveyed regarding their sexual history, risk beliefs, and
      likelihood of accepting hypothetical HIV vaccines. RESULTS: Multivariate
      regression analysis indicated that vaccine acceptability was predicted by
      lifetime sexual partners, high perceived HIV susceptibility, low danger
      invulnerability, and high psychological invulnerability. Low perceived risk was
      associated with basing decisions on vaccine cost. CONCLUSIONS: HIV vaccine
      acceptability was predicted by behavioral risk and perceived HIV susceptibility,
      but also by general feelings of invulnerability to physical and psychological
      harm.

PMID- 19182985
TI  - A review of the impacts of health and health behaviors on women's alcohol use.
AB  - OBJECTIVES: To summarize longitudinal research regarding physical health and
      health behaviors on women's subsequent alcohol use. METHODS: Medline/PsycINFO
      databases were searched; from over 5000 articles, 29 met inclusion criteria.
      RESULTS: Prior consumption and substance use are strong predictors of later
      consumption. Prior consumption was also reported to moderate the relationship
      between other health/health behaviors variables and consumption. Perception of
      one's health status may be important in modifying consumption patterns among some
      subgroups. CONCLUSIONS: Routine alcohol screening may help identify women at risk
      of developing harmful alcohol use. Mechanisms to reduce alcohol access among
      young women should be supported.

PMID- 19182987
TI  - Psychometric properties of the commitment to physical activity scale.
AB  - OBJECTIVE: To assess psychometric properties of the Commitment to Physical
      Activity Scale (CPAS). METHODS: Girls in third to fifth grades (n = 932)
      completed the CPAS before and after a physical activity intervention.
      Psychometric measures included internal consistency, factor analysis, and
      concurrent validity. RESULTS: Three CPAS factors emerged: values, attitudes, and
      motivation, with reliability coefficients ranging from .429 to .821. Significant
      correlations existed between subscales and physical activity frequency.
      CONCLUSIONS: The CPAS was reliable and valid and in a sample of third-to fifth
      grade girls. Findings support using the CPAS for measuring overall commitment to
      physical activity in girls.

PMID- 19182986
TI  - Predictors of cervical cancer screening among urban African Americans and
      Latinas.
AB  - OBJECTIVES: To assess predictors of cervical cancer screening among African
      American and Latina women, a needs assessment survey was conducted, exploring
      screening behavior, knowledge, and access to health care. METHODS: Participants
      (N = 248) were recruited at community health fairs, tenants' association
      meetings, senior centers, and community health clinics to complete a
      questionnaire. The findings from 194 African American and Latina women are
      reported. RESULTS: Neither insurance nor physician referral for screening played
      a role in obtaining cervical cancer screening. Spoken language was influential.
      CONCLUSION: The findings can now inform interventions to increase screening in
      this population.

PMID- 19182988
TI  - Retention and protocol adherence of Hispanic volunteers in a longitudinal trial.
AB  - OBJECTIVES: To compare Hispanic research volunteers with high and low levels of
      study retention and adherence. METHODS: Correlational analysis of demographics,
      recruitment strategies, knowledge, and attitudes of 470 households in a clinical
      trial. RESULTS: Within 12 months, 53 (11.3%) households dropped out; those less
      certain about some factual information were more likely to drop out (P < 0.05).
      Participants born outside the United States were more likely to adhere to
      protocols (P = 0.03). Flyers were effective for recruiting only 3% of
      participants. CONCLUSIONS: In newly immigrated populations, written recruitment
      materials may be ineffective; knowledge and attitudes may be important for study
      retention and adherence.

PMID- 19182989
TI  - Telephone counseling and home telemonitoring: the Weigh by Day Trial.
AB  - OBJECTIVE: To test the effects of telephone counseling and telemonitoring on
      weight loss. METHODS: A randomized-controlled trial was conducted over 18 months.
      Participants were assigned to an immediate or delayed-start group. The
      intervention included a Thin-Link((R)) home telemonitoring scale and biweekly
      telephone counseling over 6 months. RESULTS: The immediate group lost
      significantly more weight relative to the delayed group over the first 6 months (
      7.5 versus +1.3 pounds) and at subsequent visits. CONCLUSION: Compared to no
      treatment, the intervention was effective at producing weight loss. Home
      telemonitoring may enhance standard weight-loss counseling.

PMID- 19182990
TI  - Validity evidence for the Salutogenic Wellness Promotion Scale (SWPS).
AB  - OBJECTIVES: To test the validity, reliability, and uses of the multidimensional
      Salutogenic Wellness Promotion Scale (SWPS). METHODS: Self-reported (n = 2140)
      demographic and scale data from a large university (23,000+ students) were
      collected and analyzed. Dependent measures included grade point average (GPA) and
      perceived health. RESULTS: Analyses confirmed the SWPS's 7-factor
      multidimensional structure and its use for describing and predicting associated
      outcomes. The analyses of frequency distributions, means, correlations, and
      regressions found significant relationships between measured health behaviors,
      perceived health, and GPA. CONCLUSIONS: The SWPS provides valid and reliable
      information about positive health potential for research and field health
      professionals.

PMID- 19182991
TI  - ViewPoint: conversation with Kenneth R. McLeroy, PhD. by David R. Black and Molly
      T. Laflin.

PMID- 19182993
TI  - Characterization and kinetics of phosphopantothenoylcysteine synthetase from
      Enterococcus faecalis.
AB  - The enzyme phosphopantothenoylcysteine synthetase (PPCS) catalyzes the nucleotide
      dependent formation of phosphopantothenoylcysteine from (R)-phosphopantothenate
      and L-cysteine in the biosynthetic pathway leading to the formation of the
      essential biomolecule, coenzyme A. The Enterococcus faecalis gene coaB encodes a
      novel monofunctional PPCS which has been cloned into pET23a and expressed in
      Escherichia coli BL21 AI. The heterologous expression system yielded 30 mg of
      purified PPCS per liter of cell culture. The purified enzyme chromatographed as a
      homodimer of 28 kDa subunits on Superdex HR 200 gel filtration resin. The
      monofunctional protein displayed a nucleotide specificity for cytidine 5'
      triphosphate (CTP) analogous to that seen for bifunctional PPCS expressed by most
      prokaryotes. Kinetic characterization, utilizing initial velocity and product
      inhibition studies, found the mechanism of PPCS to be Bi Uni Uni Bi Ping-Pong,
      with the nucleotide CTP binding first and CMP released last. Michaelis constants
      were 156, 17, and 86 microM for CTP, (R)-phosphopantothenate, and L-cysteine,
      respectively, and the k(cat) was 2.9 s(-1). [carboxyl-(18)O]Phosphopantothenate
      was prepared by hydrolysis of methyl pantothenate with Na(18)OH, followed by
      enzymatic phosphorylation with E. faecalis pantothenate kinase (PanK). The fate
      of the carboxylate oxygen of labeled phosphopantothenate, during the course of
      the PPCS-catalyzed reaction with CTP and L-cysteine, was monitored by (31)P NMR
      spectroscopy. The results show that the carboxylate oxygen of the
      phosphopantothenate is recovered with the CMP formed during the reaction,
      indicative of the formation of a phosphopantothenoyl cytidylate catalytic
      intermediate, which is consistent with the kinetic mechanism.

PMID- 19182994
TI  - Ha-ras oncogene-induced Stat3 phosphorylation enhances oncogenicity of the cell.
AB  - The ras oncogene needs a second factor to induce transformation and
      tumorigenicity of the cell. In this study, we show that mouse fibroblast 7-4
      Stat3C cells overexpressing both Ha-ras(val12) oncogene and active-form Stat3
      (Stat3C) showed higher colony formation in soft agar and xenograft tumor growth
      in BALB/c mice. Further studies show that both serine-727 and tyrosine-705 of
      Stat3 were phosphorylated while Ha-ras was overexpressed. Interleukin-6 (IL-6)
      induced phosphorylation of tyrosine-705 and serine-727, as well as DNA-binding
      and transcriptional activity of Stat3 were further enhanced by Ha-ras
      overexpression. In addition, overexpression of Stat3C in 7-4-Stat3C cells
      prevented the cells from morphological change and apoptosis triggered by the Ha
      ras oncogene under serum-depleted conditions. We demonstrate that Ha-ras and
      Stat3 acting together synergistically induce Stat3 phosphorylation at serine-727
      phosphorylation and cyclin D1 expression and further enhance transformation and
      tumorigenicity of the cell. Ha-ras-induced Stat3 phosphorylation at serine-727
      plays a pivotal role in transcriptional activation of cyclin D1 and suppression
      of cell apoptosis. The effect of Ha-ras on Stat3 phosphorylation at serine-727
      was also detected in human bladder (T24) and lung (H460) cancer cells. Stat3
      phosphorylation at serine-727 is important in Ras-related tumorigenesis.

PMID- 19182995
TI  - An efficient, second-generation synthesis of the signature
      dioxabicyclo[3.2.1]octane core of (+)-sorangicin A and elaboration of the (Z,Z,E)
      triene acid system.
AB  - An efficient, second-generation synthesis of the signature
      dioxabicyclo[3.2.1]octane core of (+)-sorangicin A (1), in conjunction with an
      effective, stereocontrolled protocol to arrive at the requisite (Z,Z,E)-triene
      acid system has been developed. Highlights of the core construction entail a
      three-component union, a KHMDS-promoted epoxide ring formation-ring opening
      cascade, a Takai olefination, and a chemoselective Sharpless dihydroxylation.
      Assembly of the triene acid system was then achieved via Stille cross-coupling
      with the ethyl ester of (Z,Z)-5-tributylstannyl-2,4-pentadienoic acid, followed
      by mild hydrolysis preserving the triene configuration.

PMID- 19182996
TI  - Generation of recombinant vaccinia viruses via green fluorescent protein
      selection.
AB  - We developed a rapid method to generate recombinant vaccinia viruses (rVVs) based
      upon a bicistronic cassette encoding the gene for green fluorescent protein (GFP)
      and a foreign gene of interest separated by an internal ribosome entry site
      (IRES). As proof-of-concept, we inserted a mutant env gene of human
      immunodeficiency virus (HIV) into the cassette, which was cloned into the
      vaccinia virus (VV) insertion vector pSC59 under the control of the early-late VV
      synthetic promoter and flanked by disrupted tk gene sequences. To generate rVVs,
      293T cells were inoculated with wild-type (wt) VV, followed by transfection of
      the modified pSC59 vector containing the bicistronic cassette, which allows
      expression of GFP and the protein of interest. Next, GFP-positive cells were
      isolated by flow cytometry or by picking under a fluorescent microscope.
      Thymidine kinase-deficient (Tk(-)) 143B cells were then exposed to lysates of GFP
      positive 293T cells and cultured in the presence of bromodeoxyuridine. This
      selection allows only Tk(-) rVV to remain viable. We demonstrated the success of
      this GFP selection strategy by expressing high levels of mutant HIV Env. Our
      approach shortens the time needed to generate rVVs and represents a practical
      approach to generate recombinant proteins.

PMID- 19182997
TI  - Chemoselectivity: the mother of invention in total synthesis.
AB  - IUPAC defines chemoselectivity as "the preferential reaction of a chemical
      reagent with one of two or more different functional groups", a definition that
      describes in rather understated terms the single greatest obstacle to complex
      molecule synthesis. Indeed, efforts to synthesize natural products often become
      case studies in the art and science of chemoselective control, a skill that
      nature has practiced deftly for billions of years but man has yet to master.
      Confrontation of one or perhaps a collection of functional groups that are either
      promiscuously reactive or stubbornly inert has the potential to unravel an entire
      strategic design. One could argue that the degree to which chemists can control
      chemoselectivity pales in comparison to the state of the art in stereocontrol. In
      this Account, we hope to illustrate how the combination of necessity and tenacity
      leads to the invention of chemoselective chemistry for the construction of
      complex molecules. In our laboratory, a premium is placed upon selecting targets
      that would be difficult or impossible to synthesize using traditional techniques.
      The successful total synthesis of such molecules demands a high degree of
      innovation, which in turn enables the discovery of new reactivity and principles
      for controlling chemoselectivity. In devising an approach to a difficult target,
      we choose bond disconnections that primarily maximize skeletal simplification,
      especially when the proposed chemistry is poorly precedented or completely
      unknown. By choosing such a strategy--rather than adapting an approach to fit
      known reactions--innovation and invention become the primary goal of the total
      synthesis. Delivery of the target molecule in a concise and convergent manner is
      the natural consequence of such endeavors, and invention becomes a prerequisite
      for success.

PMID- 19182998
TI  - Plant orthoesters.

PMID- 19183000
TI  - Mycoflora and mycotoxin production in oilseed cakes during farm storage.
AB  - Agricultural activities involve the use of oilseed cakes as a source of proteins
      for livestock. Because the storage of oilseed cakes could induce the development
      of molds and the production of mycotoxins, a survey was conducted during the 5
      months of farm storage. Mycoflora was studied by microscopic examinations, and
      the presence of Aspergillus fumigatus was confirmed by polymerase chain reaction.
      A multimycotoxin method was developed to quantify seven mycotoxins (aflatoxin
      B(1), alternariol, fumonisin B(1), gliotoxin, ochratoxin A, T-2 toxin, and
      zearalenone) in oilseed cakes by high-performance liquid chromatography coupled
      to mass spectrometry. Among 34 fungal species identified, A. fumigatus and
      Aspergillus repens were observed during 5 and 4 months, respectively. Gliotoxin,
      an immunosuppressive mycotoxin, was quantified in oilseed cakes up to 45
      microg/kg, which was associated with the presence of toxigenic isolates of A.
      fumigatus.

PMID- 19182999
TI  - A hierarchy of homodesmotic reactions for thermochemistry.
AB  - Chemical equations that balance bond types and atom hybridization to different
      degrees are often used in computational thermochemistry, for example, to increase
      accuracy when lower levels of theory are employed. We expose the widespread
      confusion over such classes of equations and demonstrate that the two most widely
      used definitions of "homodesmotic" reactions are not equivalent. New definitions
      are introduced, and a consistent hierarchy of reaction classes (RC1-RC5) for
      hydrocarbons is constructed: isogyric (RC1) superset of isodesmic (RC2) superset
      of hypohomodesmotic (RC3) superset of homodesmotic (RC4) superset of
      hyperhomodesmotic (RC5). Each of these successively conserves larger molecular
      fragments. The concept of isodesmic bond separation reactions is generalized to
      all classes in this hierarchy, providing a unique sectioning of a given molecule
      for each reaction type. Several ab initio and density functional methods are
      applied to the bond separation reactions of 38 hydrocarbons containing five or
      six carbon atoms. RC4 and RC5 reactions provide bond separation enthalpies with
      errors consistently less than 0.4 kcal mol(-1) across a wide range of theoretical
      levels, performing significantly better than the other reaction types and far
      superior to atomization routes. Our recommended bond separation reactions are
      demonstrated by determining the enthalpies of formation (at 298 K) of 1,3,5
      hexatriyne (163.7 +/- 0.4 kcal mol(-1)), 1,3,5,7-octatetrayne (217.5 +/- 0.6 kcal
      mol(-1)), the larger polyynes C(10)H(2) through C(26)H(2), and an infinite
      acetylenic carbon chain.

PMID- 19183001
TI  - Identifying network of drug mode of action by gene expression profiling.
AB  - Drug mode of action (MOA) of novel compounds has been predicted using phenotypic
      features or, more recently, comparing side effect similarities. Attempts to use
      gene expression data in mammalian systems have so far met limited success. Here,
      we built a drug similarity network starting from a public reference dataset
      containing genome-wide gene expression profiles (GEPs) following treatments with
      more than a thousand compounds. In this network, drugs sharing a subset of
      molecular targets are connected by an edge or lie in the same community. Our
      approach is based on a novel similarity distance between two compounds. The
      distance is computed by combining GEPs via an original rank-aggregation method,
      followed by a gene set enrichment analysis (GSEA) to compute similarity between
      pair of drugs. The network is obtained by considering each compound as a node,
      and adding an edge between two compounds if their similarity distance is below a
      given significance threshold. We show that, despite the complexity and the
      variety of the experimental conditions, our approach is able to identify
      similarities in drug mode of action from GEPs. Our approach can also be used for
      the identification of the MOA of new compounds.

PMID- 19183002
TI  - Revealing biological modules via graph summarization.
AB  - The division of a protein interaction network into biologically meaningful
      modules can aid with automated detection of protein complexes and prediction of
      biological processes and can uncover the global organization of the cell. We
      propose the use of a graph summarization (GS) technique, based on graph
      compression, to cluster protein interaction graphs into biologically relevant
      modules. The method is motivated by defining a biological module as a set of
      proteins that have similar sets of interaction partners. We show this definition,
      put into practice by a GS algorithm, reveals modules that are more biologically
      enriched than those found by other methods. We also apply GS to predict complex
      memberships, biological processes, and co-complexed pairs and show that in most
      settings GS is preferable over existing methods of protein interaction graph
      clustering.

PMID- 19183003
TI  - Generating realistic in silico gene networks for performance assessment of
      reverse engineering methods.
AB  - Reverse engineering methods are typically first tested on simulated data from in
      silico networks, for systematic and efficient performance assessment, before an
      application to real biological networks. In this paper, we present a method for
      generating biologically plausible in silico networks, which allow realistic
      performance assessment of network inference algorithms. Instead of using random
      graph models, which are known to only partly capture the structural properties of
      biological networks, we generate network structures by extracting modules from
      known biological interaction networks. Using the yeast transcriptional regulatory
      network as a test case, we show that extracted modules have a biologically
      plausible connectivity because they preserve functional and structural properties
      of the original network. Our method was selected to generate the "gold standard"
      networks for the gene network reverse engineering challenge of the third DREAM
      conference (Dialogue on Reverse Engineering Assessment and Methods 2008,
      Cambridge, MA).

PMID- 19183004
TI  - Integrating biological knowledge with gene expression profiles for survival
      prediction of cancer.
AB  - Due to the large variability in survival times between cancer patients and the
      plethora of genes on microarrays unrelated to outcome, building accurate
      prediction models that are easy to interpret remains a challenge. In this paper,
      we propose a general strategy for improving performance and interpretability of
      prediction models by integrating gene expression data with prior biological
      knowledge. First, we link gene identifiers in expression dataset with gene
      annotation databases such as Gene Ontology (GO). Then we construct "supergenes"
      for each gene category by summarizing information from genes related to outcome
      using a modified principal component analysis (PCA) method. Finally, instead of
      using genes as predictors, we use these supergenes representing information from
      each gene category as predictors to predict survival outcome. In addition to
      identifying gene categories associated with outcome, the proposed approach also
      carries out additional within-category selection to select important genes within
      each gene set. We show, using two real breast cancer microarray datasets, that
      the prediction models constructed based on gene sets (or pathway) information
      outperform the prediction models based on expression values of single genes, with
      improved prediction accuracy and interpretability.

PMID- 19183005
TI  - How to synchronize biological clocks.
AB  - This paper is concerned with a novel algorithm to study networks of biological
      clocks. A new set of conditions is established that can be used to verify whether
      an existing network synchronizes or to give guidelines to construct a new
      synthetic network of biological oscillators that synchronize. The methodology
      uses the so-called contraction theory from dynamical system theory and Gershgorin
      disk theorem. The strategy is validated on two examples: a model of glycolisis in
      yeast cells and a synthetic network of Repressilators that synchronizes.

PMID- 19183006
TI  - Flexible polar nanowires of Cs5BiP4Se12 from weak interactions between
      coordination complexes: strong nonlinear optical second harmonic generation.
AB  - The Cs(5)BiP(4)Se(12) salt grows naturally as nanowires that crystallize in the
      polar space group Pmc2(1), with a = 7.5357(2) A, b = 13.7783(6) A, c = 28.0807(8)
      A, and Z = 4 at 293(2) K. The compound features octahedral [Bi(P(2)Se(6))(2)](5-)
      coordination complexes that stack via weak intermolecular Se...Se interactions to
      form long, flexible fibers and nanowires. The Cs(5)BiP(4)Se(12) fibers are
      transparent in the near- and mid-IR ranges and were found to exhibit a nonlinear
      optical second harmonic generation response at 1 microm that is approximately
      twice that of the benchmark material AgGaSe(2). The material has a nearly direct
      band gap of 1.85 eV and melts congruently at 590 degrees C. Ab initio electronic
      structure calculations performed with the full-potential linearized augmented
      plane wave (FLAPW) method show that the band gap increases from its local density
      approximation (LDA) spin-orbit coupling value of 1.15 eV to the higher value of
      2.0 eV when the screened-exchange LDA method is invoked and explain how the long
      nanowire nature of Cs(5)BiP(4)Se(12) emerges.

PMID- 19183007
TI  - Anatomy of phobanes. diastereoselective synthesis of the three isomers of n
      butylphobane and a comparison of their donor properties.
AB  - Three methods for the large scale (50-100 g) separation of the secondary phobanes
      9-phosphabicyclo[3.3.1]nonane (s-PhobPH) and 9-phosphabicyclo[4.2.1]nonane (a
      PhobPH) are described in detail. Selective protonation of s-PhobPH with aqueous
      HCl in the presence of a-PhobPH is an efficient way to obtain large quantities of
      a-PhobPH. Selective oxidation of a-PhobPH in an acidified mixture of a-PhobPH and
      s-PhobPH is an efficient way to obtain large quantities of s-PhobPH. The
      crystalline, air-stable phosphonium salts [s-PhobP(CH(2)OH)(2)]Cl and [a
      PhobP(CH(2)OH)(2)]Cl can be separated by a selective deformylation with aqueous
      NaOH. a-PhobPH is shown to be a(5)-PhobPH in which the H lies over the five
      membered ring. The isomeric a(7)-PhobPH has been detected but isomerizes to a(5)
      PhobPH rapidly in the presence of water. s-PhobPH is more basic than a-PhobPH by
      about 2 pK(a) units in MeOH. Treatment of s-PhobPH with BH(3).THF gives s
      PhobPH(BH(3)) and similarly a-PhobPH gives a(5)-PhobPH(BH(3)). Isomerically pure
      s-PhobPCl and a(5)-PhobPCl are prepared by reaction of the corresponding PhobPH
      with C(2)Cl(6). The n-butyl phobane s-PhobPBu is prepared by nucleophilic (using
      s-PhobPH or s-PhobPLi) and electrophilic (using s-PhobPCl) routes. Isomerically
      pure a(5)-PhobPBu is prepared by treatment of a-PhobPLi with (n)BuBr and a(7)
      PhobPBu is prepared by quaternization of a-PhobPH with (n)BuBr followed by
      deprotonation. From the rates of conversion of a(7)-PhobPBu to a(5)-PhobPBu, the
      DeltaG(double dagger) (403 K) for P-inversion is calculated to be 38.1 kcal mol(
      1) (160 kJ mol(-1)). The donor properties of the individual isomers of PhobPBu
      were assessed from the following spectroscopic measurements: (i) (1)J(PSe) for
      PhobP(Se)Bu; (ii) nu(CO) for trans-[RhCl(CO)(PhobPBu)(2)], (iii) (1)J(PtP) for
      the PEt(3) in trans-[PtCl(2)(PEt(3))(PhobPBu)]. In each case, the data are
      consistent with the order of sigma-donation being a(7)-PhobPBu > s-PhobPBu > a(5)
      PhobPBu. This same order was found when the affinity of the PhobPBu isomers for
      platinum(II) was investigated by determining the relative stabilities of
      [Pt(CH(3))(s-PhobPBu)(dppe)][BPh(4)], [Pt(CH(3))(a(5)-PhobPBu)(dppe)][BPh(4)],
      and [Pt(CH(3))(a(7)-PhobPBu)(dppe)][BPh(4)] from competition experiments.
      Calculations of the relative stabilities of the isomers of PhobPH,
      [PhobPH(2)](+), and PhobPH(BH(3)) support the conclusions drawn from the
      experimental results. Moreover, calculations on the frontier orbital energies of
      PhobPMe isomers and their binding energies to H(+), BH(3), PdCl(3)(-), and
      PtCl(3)(-) corroborate the experimental observation of the order of sigma
      donation being a(7)-PhobPR > s-PhobPR > a(5)-PhobPR. The calculated He(8) steric
      parameter shows that the bulk of the isomers increases in the order a(7)-PhobPR <
      s-PhobPR < a(5)-PhobPR. The crystal structures of [a-PhobP(CH(2)OH)(2)][s
      PhobP(CH(2)OH)(2)]Cl(2), cis-[PtCl(2)(a(5)-PhobPCH(2)OH)(2)], trans-[PtCl(2)(s
      PhobPBu)(2)], and trans-[PtCl(2)(a(7)-PhobPBu)(2)] are reported.

PMID- 19183018
TI  - Liposome-prilocaine interaction mapping evaluated through STD NMR and molecular
      dynamics simulations.
AB  - We have examined the interaction of the neutral and protonated species of the
      local anesthetic prilocaine (PLC) with phosphatidylcholine (PC) bilayers
      combining experimental ((1)H NMR) and theoretical (molecular dynamics
      simulations) approaches. DOSY experiments allowed the determination of the
      association constants of protonated (Ka = 9 L/mol) and neutral (Ka = 21 L/mol)
      PLC to egg PC liposomes. Saturation transfer difference (STD) experiments showed
      a different trend depending on pH: At high pH the PLC hydrogen saturation was
      essentially uniform and at pH 5.5 the experiments show an enhancement of the
      aromatic moiety hydrogen saturation, with respect to the tail. Molecular dynamics
      simulations, performed with PLC molecules on planar bilayers of palmitoyloleyl
      PC, revealed a preferential orientation for the protonated PLC species at the
      polar interface of the bilayer, and a nonoriented and deeper insertion for
      neutral PLC. Such preferential location of protonated and neutral PLC inside the
      bilayer can be described as different transient sites which could modulate the
      access of these molecules to their binding site(s) in the voltage-gated sodium
      channel, justifying differences in the anesthetic's potency upon ionization.

PMID- 19183036
TI  - Copper-intercalated TiS2: electrode materials for rechargeable batteries as
      future power resources.
AB  - We report results of first-principles total-energy calculations of structural and
      optical properties of the TiS(2) single crystals intercalated with copper.
      Calculations have been performed using an all-electron, full potential,
      linearized, augmented, plane-wave method based on density functional theory using
      generalized gradient approximation for the exchange correlation energy
      functional. To complete the fundamental characteristics of these compounds, we
      have calculated and analyzed their linear optical susceptibilities. We
      demonstrate the efficiency of using a full potential on the band structure,
      density of states, and the optical properties. We compare our results of the
      intercalated Cu in different sites and concentrations with the host TiS(2)
      compound to ascertain the effect of Cu intercalation on the electronic and
      optical properties. Our calculations have shown that the electronic and optical
      properties are influenced significantly by the location and concentration of the
      Cu intercalate in the host compound. The Cu-s and Cu-p bands are very broad and
      do not contribute much to the density of states. The density of states and the
      electron charge density show that all Ti-Ti and S-S bonds are basically of ionic
      character and that Ti-S bonds are of covalent character. No covalent electrons
      are found between Cu and S atoms; that is, no covalent bond exists between the Cu
      and S atoms. The Cu atoms are ionic in the intercalated compounds.

PMID- 19183037
TI  - New strategies for protecting group chemistry: synthesis, reactivity, and
      indirect oxidative cleavage of para-siletanylbenzyl ethers.
AB  - Reported herein is a new entry in the growing arsenal of arylmethyl ether
      protecting groups. The para-siletanylbenzyl (PSB) ether is electronically similar
      to the benzyl ether. Cleavage of the PSB ether is accomplished under mild
      conditions--involving alkaline hydrogen peroxide--that are unique among cleavage
      protocols for arylmethyl ethers. Furthermore, the PSB group affords the user new
      flexibility in the implementation of protecting group strategies that revolve
      around multiple arylmethyl ether protecting groups. In addition to hydrogen
      peroxide-based cleavage protocols, conversion of a PSB ether into a para
      methoxybenzyl (PMB) ether and assembly of a PSB ether from a pre-existing para
      bromobenzyl (PBB) ether are described. Finally, a new reagent for installing PSB
      ethers under neutral "mix and heat" conditions is reported.

PMID- 19183038
TI  - Multiple bonding in the chromium dimer supported by two diazadiene ligands.
AB  - Analysis of the topology and delocalization of the electron density with the
      quantum theory of atoms in molecules (QTAIM) shows that the Cr(2) dimer when
      supported by two diazadiene ligands has a degree of bonding of 3.6--slightly less
      than that of a formal quadruple bond. The metal-ligand complex is held together
      by relatively weak dative bonds. Out-of-plane lone-pair-like charge
      concentrations on the nitrogen atoms are oriented so as to maximally avoid areas
      of charge concentration in the distorted inner-valence shell of the chromium
      atoms.

PMID- 19183039
TI  - Highly stable indomethacin glasses resist uptake of water vapor.
AB  - Mass uptake of water vapor was measured as a function of relative humidity for
      indomethacin glasses prepared using physical vapor deposition at different
      substrate temperatures. Highly stable glasses were produced on substrates at 265
      K (0.84Tg) by depositing at 0.2 nm/s while samples similar to melt-cooled glasses
      were produced at 315 K and 5 nm/s. Samples deposited at 315 K absorb
      approximately the same amount of water as glasses prepared by supercooling the
      melt while stable glasses absorb a factor of 5 less water. Unexpectedly, the
      diffusion of water in the stable glass samples is 5-10 times faster than in the
      glass prepared by cooling the liquid.

PMID- 19183040
TI  - Nanospheres with polymerization ability coated by polyrotaxane.
AB  - BETA-cyclodextrin (beta-CD)-based nanosphere 1 initiated the oligomerization of
      delta-valerolactone (delta-VL) on the surface of 1 to give oligo(delta-VL)
      tethered beta-CD nanosphere 2 in bulk. Atomic force microscopy indicated that the
      molecular size of 2 is twice that of 1. The addition of alpha-CD to 2 leads to
      the formation of poly-pseudo-rotaxane on the surface of 2 to give a nanosphere
      with poly-pseudo-rotaxane (alpha-CD[symbol: see text]2). 2D-NOESY NMR experiments
      showed correlation peaks between the inner protons of alpha-CD and the
      oligo(delta-VL) chains in an aqueous solution, indicating that the oligo(delta
      VL) chains are included in the alpha-CD cavity. Alpha-CD[symbol: see text]2 has a
      core of beta-CDs with poly-pseudo-rotaxanes on the surface. It should be noted
      that 2 did not show polymerization ability for delta-VL, but after the formation
      of poly-pseudo-rotaxanes, oligo(delta-VL) of alpha-CD[symbol: see text]2
      repropagated upon the addition of delta-VL. Alpha-CD[symbol: see text]2 is
      significantly larger than nanospheres 1 and 2. Additionally, postpolymerization
      increases the size of alpha-CD[symbol: see text]2. These behaviors are
      reminiscent of the function of a spherical virus, which forms an ordered
      spherical structure and releases RNA chains from the capsid surface.

PMID- 19183041
TI  - Automated global mapping of minimal energy points on seams of crossing by the
      anharmonic downward distortion following method: a case study of H2CO.
AB  - Automated global mapping of minimal energy points on seams of crossing (MSX
      structures) were performed by using the anharmonic downward distortion following
      (ADD-following) method, which has previously been applied to the single potential
      energy surfaces (PESs) to perform automated global reaction route mapping. In
      this study, the ADD-following is applied to a penalty function based on two PESs
      of different electronic states. The present approach is effective not only for
      crossing seams between states with different symmetry but also for conical
      intersections for states with the same symmetry. Many new MSX structures were
      discovered on the S(0)/T(1) and S(1)/T(1) crossing seams and the S(0)/S(1)
      conical intersections of H(2)CO by automated global mapping using the ADD
      following method. A possible pathway for dissociation of formaldehyde excited to
      S(1) at low energy is discussed.

PMID- 19183042
TI  - Interaction of carbon monoxide with the apoptosis-inducing cytochrome c
      cardiolipin complex.
AB  - The interaction of mitochondrial cytochrome (cyt) c with cardiolipin (CL) is
      involved in the initial stages of apoptosis. This interaction can lead to
      destabilization of the heme-Met80 bond and peroxidase activity [Basova, L. V., et
      al. (2007) Biochemistry 46, 3423-3434]. We show that under these conditions
      carbon monoxide (CO) binds to cyt c, with very high affinity ( approximately 5 x
      10(7) M(-1)), in contrast to the native cyt c protein involved in respiratory
      electron shuttling that does not bind CO. Binding of CO to the cyt c-CL complex
      inhibits its peroxidase activity. Photodissociated CO from the cyt c-CL complex
      shows <20% picosecond geminate rebinding and predominantly bimolecular rebinding,
      with a second-order rate constant of approximately 10(7) M(-1) s(-1), an order of
      magnitude higher than in myoglobin. These findings contrast with those of Met80X
      mutant cyt c, where picosecond geminate recombination dominates due to the
      rigidity of the protein. Our data imply that CL leads to substantial changes in
      protein conformation and flexibility, allowing access of ligands to the heme.
      Together with the findings that (a) approximately 30 CL per cyt c are required
      for full CO binding and (b) salt-induced dissociation indicates that the two
      negative headgroup charges interact with approximately 5 positive surface charges
      of the protein, these results are consistent with a CL anchorage model with an
      acyl chain impaled in the protein [Kalanxhi, E., and Wallace, C. J. A. (2007)
      Biochem. J. 407, 179-187]. The affinity of CO for the complex is high enough to
      envisage an antiapoptotic effect of nanomolar CO concentrations via inhibition of
      the cyt c peroxidase activity.

PMID- 19183043
TI  - Novel pyrrolidine ureas as C-C chemokine receptor 1 (CCR1) antagonists.
AB  - Monocyte infiltration is implicated in a variety of diseases including multiple
      myeloma, rheumatoid arthritis, and multiple sclerosis. C-C chemokine receptor 1
      (CCR1) is a chemokine receptor that upon stimulation, particularly by macrophage
      inflammatory protein 1alpha (MIP-1alpha) and regulated on normal T-cell expressed
      and secreted (RANTES), mediates monocyte trafficking to sites of inflammation.
      High throughput screening of our combinatorial collection identified a novel,
      moderately potent CCR1 antagonist 3. The library hit 3 was optimized to the
      advanced lead compound 4. Compound 4 inhibited CCR1 mediated chemotaxis of
      monocytes with an IC(50) of 20 nM. In addition, the compound was highly selective
      over other chemokine receptors. It had good microsomal stability when incubated
      with rat and human liver microsomes and showed no significant cytochrome P450
      (CYP) inhibition. Pharmacokinetic evaluation of the compound in the rat showed
      good oral bioavailability.

PMID- 19183045
TI  - High-lamellar ordering and amorphous-like pi-network in short-chain
      thiazolothiazole-thiophene copolymers lead to high mobilities.
AB  - Owing to their superior transport properties, poly(alkylthiophenes) and their
      derivatives emerged as one of the most widely studied semiconducting polymers
      with potential applications in organic electronics. It is now generally
      acknowledged that one of the particularly effective ways to increase the carrier
      mobility in these materials is by increasing the length of the conjugated
      backbones. Some recent reports suggest also that carrier mobilities can be
      further enhanced by highly crystalline arrangement (and interdigitation) of alkyl
      side chains possibly because it promotes the formation of extensive layered
      structures favorable for carrier transport. Results presented here demonstrate
      that, surprisingly, none of these factors are actually necessary for good
      electronic performance of polythiophene-like systems. Thiophene-based
      semiconducting polymers bearing thiazolothiazole unit (PTzQT) described here were
      shown to have very high carrier mobilities (approximately 0.3 cm(2)/Vs) despite
      their low molecular weight and uneven spacing of alkyl side chains, which
      suppressed high side chain crystallinity/interdigitation as revealed by thermal
      analysis and X-ray scattering. The highly disordered nature of these materials
      extended to the nanoscale level as evident from atomic force microscopy images,
      which have shown only the presence of small domains packed into isotropic
      amorphous-like superstructures with lateral correlation lengths increasing with
      the length of alkyl side chains. The observed concomitant increase of carrier
      mobilities points to the possible role of characteristic length of surface
      roughness as the key parameter controlling carrier transport in disordered,
      noninterdigitating systems.

PMID- 19183046
TI  - Structure of propeller-type parallel-stranded RNA G-quadruplexes, formed by human
      telomeric RNA sequences in K+ solution.
AB  - Very recent studies showed that mammalian telomeres were transcribed into
      telomeric-repeat-containing RNAs and suggested that these RNA molecules were
      biologically important. Here we report on a structural study of RNA G
      quadruplexes formed by human telomeric RNA sequences in K(+) solution. Our data
      indicated that these sequences formed propeller-type parallel-stranded RNA G
      quadruplexes. We have determined the NMR-based solution structure of a dimeric
      propeller-type RNA G-quadruplex formed by the 12-nt human telomeric RNA sequence
      r(UAGGGUUAGGGU). We also observed the stacking of two such propeller-type G
      quadruplex blocks for the 10-nt human telomeric RNA sequence r(GGGUUAGGGU) and a
      higher-order G-quadruplex structure for the 9-nt human telomeric RNA sequence
      r(GGGUUAGGG). Based on these findings we proposed how higher-order structures
      might be formed by long telomeric RNA.

PMID- 19183047
TI  - Structural revision of stemoburkilline from an E-alkene to a Z-alkene.
AB  - Semisynthesis studies starting from (11Z)-1',2'-didehydrostemofoline (4)
      indicated that the known Stemona alkaloid stemoburkilline is the Z-isomer and not
      the E-isomer as initially reported. The semisynthesis involved conversion of
      (11Z)-1',2'-didehydrostemofoline (4) to 11(S),12(S)-dihydrostemofoline (3)
      followed by a stereoselective base-catalyzed ring-opening reaction to give (Z)
      stemoburkilline (8). The same product was obtained using a similar synthetic
      protocol starting from isostemofoline (6) via a based-catalyzed ring-opening
      reaction of 11(S),12(R)-dihydrostemofoline (1). A re-examination of the crude
      root extracts of Stemona burkillii Prain and further NOE studies established
      stemoburkilline as the Z-isomer (8).

PMID- 19183048
TI  - Caryophyllenes from a fungal culture of Chrysosporium pilosum.
AB  - Four new caryophyllene derivatives, Sch 725432 (1), Sch 601253 (2), Sch 601254
      (3), and Sch 725434 (4), were isolated from the fungal fermentation broth of
      Chrysosporium pilosum by reversed-phase HPLC purification. The structure
      elucidation of trioxygenated caryophyllenes 1-4 was accomplished on the basis of
      spectroscopic data interpretation. Sch 725434 (4) possesses a dihydrofuran-3-one
      ring, forming a tricyclic ring skeleton, which represents an unprecedented ring
      skeleton for the caryophyllene-type of sesquiterpenes. Compounds 1-4 were
      evaluated for their antifungal activity.

PMID- 19183049
TI  - Free-standing nanocomposite multilayers with various length scales, adjustable
      internal structures, and functionalities.
AB  - We introduce an innovative and robust method for the preparation of nanocomposite
      multilayers, which allows accurate control over the placement of functional
      groups as well as the composition and dimensions of individual layers/internal
      structure. By employing the photocross-linkable polystyrene (PS-N(3), M(n) = 28.0
      kg/mol) with 10 wt % azide groups (-N(3)) for host polymer and/or the PS-N(3)-SH
      (M(n) = 6.5 kg/mol) with azide and thiol (-SH) groups for capping ligands of
      inorganic nanoparticles, nanocomposite multilayers were prepared by an efficient
      photocross-linking layer-by-layer process, without perturbing underlying layers
      and nanostructures. The thickness of individual layers could be controlled from a
      few to hundreds of nanometers producing highly ordered internal structure, and
      the resulting nanocomposite multilayers, consisting of polymer and inorganic
      nanoparticles (CdSe@ZnS, Au, and Pt), exhibit a variety of interesting physical
      properties. These include prolonged photoluminescent durability, facile color
      tuning, and the ability to prepare functional free-standing films that can have
      the one-dimensional photonic band gap and furthermore be patterned by
      photolithography. This robust and tailored method opens a new route for the
      design of functional film devices based on nanocomposite multilayers.

PMID- 19183051
TI  - Copper(I)-catalyzed synthesis of substituted 2-mercapto benzimidazoles.
AB  - An efficient method for the preparation of various substituted 2-mercapto
      benzimidazoles from their corresponding thioureas has been developed. S
      alkylation of thioureas followed by Cu-catalyzed intramolecular N-arylation
      furnished substituted 2-mercapto benzimidazoles in high yields and short reaction
      times. Furthermore, 2-mercapto benzimidazoles substituted with a p-methoxybenzyl
      group allowed access to benzimidazole thiones.

PMID- 19183054
TI  - Which human metabolites have we MIST? Retrospective analysis, practical aspects,
      and perspectives for metabolite identification and quantification in
      pharmaceutical development.
AB  - With the recent publication of the FDA guidance on metabolites in safety testing
      (MIST), a reflection is provided that describes the impact of this guidance on
      the processes of drug metabolite identification and quantification at various
      stages of drug development. First, a retrospective analysis is described that was
      conducted on 12 human absorption, metabolism, and excretion (AME) trials with the
      application of these MIST criteria. This analysis showed that the number of
      metabolites requiring identification, (semi)-quantification, and coverage in the
      toxicology species would substantially increase. However, a significant
      proportion of these metabolites were direct or indirect conjugates, a class of
      metabolites that was specifically addressed in the guidance as being largely
      innocuous. The nonconjugated metabolites were all covered in at least one
      toxicology animal species, with no need for additional safety evaluation. Second,
      analytical considerations pertaining to the efficient identification of
      metabolites are discussed. Topics include software-assisted detection and
      structural identification of metabolites, the emerging hyphenation of
      ultraperformance liquid chromatography (UPLC) with radioactivity detection, and
      the various ways to estimate metabolite abundance in the absence of an authentic
      standard. Technical aspects around the analysis of metabolite profiles are also
      presented, focusing on precautions to be taken in order not to introduce
      artifacts. Finally, a tiered approach for metabolite quantification is proposed,
      starting with quantification of metabolites prior to the multiple ascending dose
      study (MAD) in humans in only specific cases (Tier A). The following step is the
      identification and quantification of metabolites expected to be of
      pharmacological or toxicological relevance (based on MIST and other complementary
      criteria) in selected samples from the MAD study and preclinical studies in order
      to assess metabolite exposure coverage (Tier B). Finally, a metabolite
      quantification strategy for the studies after the MAD phase (Tier C) is proposed.

PMID- 19183056
TI  - Intermittent dynamics, stochastic resonance and dynamical heterogeneity in
      supercooled liquid water.
AB  - Here we find through computer simulations and theoretical analysis that the low
      temperature thermodynamic anomalies of liquid water arises from the intermittent
      fluctuation between its high density and low density forms, consisting largely of
      5-coordinated and 4-coordinated water molecules, respectively. The fluctuations
      exhibit strong dynamic heterogeneity (defined by the four point time correlation
      function), accompanied by a divergence like growth of the dynamic correlation
      length, of the type encountered in fragile supercooled liquids. The intermittency
      has been explained by invoking a two state model often employed to understand
      stochastic resonance, with the relevant periodic perturbation provided here by
      the fluctuation of the total volume of the system.

PMID- 19183057
TI  - Electrolyte-dependent electrosynthesis and activity of cobalt-based water
      oxidation catalysts.
AB  - Electrolysis of Co(2+) in phosphate, methylphosphonate, and borate electrolytes
      effects the electrodeposition of an amorphous highly active water oxidation
      catalyst as a thin film on an inert anode. Electrodeposition of a catalytically
      competent species immediately follows oxidation of Co(2+) to Co(3+) in solution.
      Methylphosphonate and borate electrolytes support catalyst activity comparable to
      that observed for phosphate. Catalytic activity for O(2) generation in aqueous
      solutions containing 0.5 M NaCl is retained for catalysts grown from phosphate
      electrolyte.

PMID- 19183053
TI  - Quantification of the vitamin D receptor-coregulator interaction.
AB  - The vitamin D receptor (VDR) regulates a diverse set of genes that control
      processes including bone mineral homeostasis, immune function, and hair follicle
      cycling. Upon binding to its natural ligand, 1alpha,25(OH)(2)D(3), the VDR
      undergoes a conformational change that allows the release of corepressor proteins
      and the binding of coactivator proteins necessary for gene transcription. We
      report the first comprehensive evaluation of the interaction of the VDR with a
      library of coregulator binding motifs in the presence of two ligands, the natural
      ligand 1alpha,25(OH)(2)D(3) and a synthetic, nonsecosteroidal agonist LG190178.
      We show that the VDR has relatively high affinity for the second and third LxxLL
      motifs of SRC1, SRC2, and SRC3 and second LxxLL motif of DRIP205. This pattern is
      distinct in comparison to other nuclear receptors. The pattern of VDR-coregulator
      binding affinities was very similar for the two agonists investigated, suggesting
      that the biologic functions of LG190178 and 1alpha,25(OH)(2)D(3) are similar.
      Hairless binds the VDR in the presence of ligand through a LxxLL motif (Hr-1),
      repressing transcription in the presence and absence of ligand. The VDR binding
      patterns identified in this study may be used to predict functional differences
      among different tissues expressing different sets of coregulators, thus
      facilitating the goal of developing tissue- and gene-specific vitamin D response
      modulators.

PMID- 19183058
TI  - Milk peptides increase iron dialyzability in water but do not affect DMT-1
      expression in Caco-2 cells.
AB  - In vitro digestion of milk produces peptide fractions that enhance iron uptake by
      Caco-2 cells. The objectives of this study were to investigate whether these
      fractions (a) exert their effect by increasing relative gene expression of DMT-1
      in Caco-2 cells and (b) enhance iron dialyzability when added in meals. Two milk
      peptide fractions that solubilize iron were isolated by Sephadex G-25 gel
      filtration of a milk digest. These peptide fractions did not affect relative gene
      expression of DMT-1 when incubated with Caco-2 cells for 2 or 48 h. Dialyzability
      was measured after in vitro simulated gastric and pancreatic digestion. Both
      peptide fractions enhanced the dialyzability of iron from ferric chloride added
      to PIPES buffer, but had no effect on dialyzability from milk or a vegetable or
      fruit meal after in vitro simulated gastric and pancreatic digestion. However,
      dialyzability from milk was enhanced by the addition of a more concentrated
      lyophilized peptide fraction.

PMID- 19183060
TI  - Intrapopulation variation in the standard metabolism of a terrestrial mollusc:
      repeatability of the CO2 production in the land snail Helix aspersa.
AB  - During the past 2 decades, interest in interindividual variation in performance
      traits has increased considerably among physiological ecologists. A great deal of
      this interest has focused on repeatability studies of physiological traits. One
      of the most important physiological traits in animals is whole-animal metabolism
      because it reflects several aspects of an organism's energy budget. However, in
      order to respond to natural selection (ultimately), this variable should be
      consistent over most of an individual's life history. We studied energy
      metabolism (CO2 production, (.-)V(CO2)) in two of the southernmost populations of
      Helix aspersa land snails, a cosmopolitan species that colonized most of the
      human-inhabited world. Our results show that H. aspersa exhibits a relatively
      lower than expected (.-)V(CO2) compared with that described in the few other
      published studies on this species and that there is no significant difference
      between populations (Valdivia (.-)V(CO2) = 0.21 +/- 0.01 mL CO2 h(-1); Concepcion
      (.-)V(CO2) = 0.20 +/- 0.01 mL CO2 h(-1); mean body mass = 4.2 g). Repeatability
      of (.-)V(CO2) in land snails was significant and was not statistically different
      in both populations (Valdivia: tau = 0.42; Concepcion: tau = 0.31). These results
      suggest that energy metabolism is repeatable and can eventually respond to
      selection in land snails. We argue that land snails are good, though
      underutilized, models for evolutionary physiology studies.

PMID- 19183066
TI  - Diversity and composition of viral communities: coinfection of barley and cereal
      yellow dwarf viruses in California grasslands.
AB  - Most species host multiple pathogens, yet field studies rarely examine the
      processes determining pathogen diversity within a single host or the effects of
      coinfection on pathogen dynamics in natural systems. Coinfection can affect
      pathogen transmission and virulence. In turn, coinfection can be regulated within
      hosts by interactions such as cross-protective immunity or at broader spatial
      scales via vector distributions. Using a general model, we demonstrate that
      coinfection by a group of vectored pathogens is highest with abundant generalist
      vectors and weak cross-protection and coinfection-induced mortality. Using these
      predictions, we investigate the distribution of five coexisting aphid-vectored,
      viral pathogens (barley and cereal yellow dwarf luteoviruses and poleroviruses)
      in a native perennial grass (Elymus glaucus) in both space (700 km) and time (4
      years). Observed coinfection rates were much higher than expected at random,
      suggesting that within-host processes exerted weak effects on within-host
      pathogen diversity. Covariance among viruses in space and time was highest for
      viral species sharing a vector. Temporal correlation arose from the synchronous
      invasion of two viruses transmitted by a shared aphid species. On the basis of
      our modeling and empirical results, we expect that factors external to individual
      hosts may affect the coinfection dynamics in other communities hosting vectored
      pathogens.

PMID- 19183067
TI  - Long-term effects of predator arrival timing on prey community succession.
AB  - The stochastic arrival of competing species and their subsequent interactions
      have been highlighted as principal forces underlying biotic historical effects in
      community assembly. However, despite the widely recognized effect of predation on
      prey communities, the effects that the stochastic arrival of predators may have
      on assembling communities are poorly understood. We used a microbial microcosm
      experiment to investigate whether the timing of predator arrival to a prey
      community undergoing naturalistic succession affected species abundances and
      community diversity. Predator arrival timing affected the long-term abundance of
      a prey species that was persistent throughout succession in the absence of
      predators. Our data indicate that this timing effect occurred indirectly via
      transient interactions between early-successional prey species and predators.
      Specifically, we suggest that transient early-successional prey species served as
      a springboard for early-arriving (but not late-arriving) predators, allowing the
      exploiting predators to increase their abundances and subsequently alter long
      term community dynamics. These results show that the history of predator arrival
      can have lasting consequences for community structure in ecological succession.

PMID- 19183069
TI  - Platelet-endothelial cell adhesion molecule-1 gene polymorphism and its soluble
      level are associated with ischemic stroke.
AB  - Inflammation, characterized by the recruitment and adhesion of circulating
      leukocytes by cellular adhesion molecules, plays an important role in the
      pathogenesis of atherosclerosis. Genetic analyses of platelet-endothelial cell
      adhesion molecule-1 (PECAM-1), a key adhesion molecule in the progression of
      atherosclerosis, have provided conflicting results regarding the role of
      variation within the PECAM-1 gene and risk for coronary heart disease. No studies
      have examined the association of this polymorphism with ischemic stroke.
      Therefore, we investigated that PECAM-1 gene polymorphism and its soluble level
      are associated with ischemic stroke in Chinese population. We analyzed single
      nucleotide polymorphisms of PECAM-1 gene Leu125Val, Asn563Ser, and Gly670Arg in
      265 patients with ischemic stroke and 280 age- and sex-matched controls, using
      polymerase chain reaction-restriction fragment length polymorphism and DNA
      sequencing method, while soluble PECAM-1 (sPECAM-1) levels were measured by
      enzyme-linked immunosorbent assay. There were significant differences in the
      genotype and allele frequencies of PECAM-1 gene Leu125Val polymorphism between
      the group of patients with ischemic stroke and the control group (p < 0.05).
      sPECAM-1 levels were increased in patients with ischemic stroke compared with
      controls (p < 0.01). Moreover, genotypes carrying the PECAM-1 125Val variant
      allele were associated with increased PECAM-1 levels compared to the homozygous
      wild-type genotype in patients with ischemic stroke. The Leu125Val polymorphism
      of PECAM-1 and its sPECAM-1 levels are associated with ischemic stroke in Chinese
      population. Our data suggest that the PECAM-1 gene may play a role in the
      development of ischemic stroke.

PMID- 19183070
TI  - Basilar invagination managed with electroacupuncture and Chinese herbal medicine:
      the report of a rare case in a pediatric patient.
AB  - BACKGROUND: A 13-year-old girl who suffered from basilar invagination managed
      with electroacupuncture and Chinese Herbal medicine is presented in this report.
      This is a rare disease. The condition was misdiagnosed by many biomedical
      specialists over a period of 5 years. There has been no literature ever recorded
      in Traditional Chinese Medicine (TCM) history for the treatment of this rare
      condition. METHODS: The patient has a secondary condition, hydrocephalus, which
      was categorized as Jie Lu from a Chinese Medicine perspective. Jie Lu has also
      been used to form the rational base of the TCM treatment. RESULTS: This patient's
      condition stabilized for a period of 3 years. As bone growth continued, the
      severity of the patient's symptoms increased. The patient has turned 19; her
      symptoms have become more severe and she is unable to walk for a short distance.
      CONCLUSIONS: Finally, a diagnosis of basilar invagination was confirmed by a
      private health service provider team separate from several public hospitals'
      specialist teams.

PMID- 19183068
TI  - Role of conserved tyrosine residues in NiSOD catalysis: a case of convergent
      evolution.
AB  - Superoxide dismutases rely on protein structural elements to adjust the redox
      potential of the metallocenter to an optimum value near 300 mV (vs NHE), to
      provide a source of protons for catalysis, and to control the access of anions to
      the active site. These aspects of the catalytic mechanism are examined herein for
      recombinant preparations of the nickel-dependent SOD (NiSOD) from Streptomyces
      coelicolor and for a series of mutants that affect a key tyrosine residue, Tyr9
      (Y9F-, Y62F-, Y9F/Y62F-, and D3A-NiSOD). Structural aspects of the nickel sites
      are examined by a combination of EPR and X-ray absorption spectroscopies, and by
      single-crystal X-ray diffraction at approximately 1.9 A resolution in the case of
      Y9F- and D3A-NiSODs. The functional effects of the mutations are examined by
      kinetic studies employing pulse radiolytic generation of O2- and by redox
      titrations. These studies reveal that although the structure of the nickel center
      in NiSOD is unique, the ligand environment is designed to optimize the redox
      potential at 290 mV and results in the oxidation of 50% of the nickel centers in
      the oxidized hexamer. Kinetic investigations show that all of the mutant proteins
      have considerable activity. In the case of Y9F-NiSOD, the enzyme exhibits
      saturation behavior that is not observed in wild-type (WT) NiSOD and suggests
      that release of peroxide is inhibited. The crystal structure of Y9F-NiSOD reveals
      an anion binding site that is occupied by either Cl- or Br- and is located close
      to but not within bonding distance of the nickel center. The structure of D3A
      NiSOD reveals that in addition to affecting the interaction between subunits,
      this mutation repositions Tyr9 and leads to altered chemistry with peroxide.
      Comparisons with Mn(SOD) and Fe(SOD) reveal that although different strategies
      for adjusting the redox potential and supply of protons are employed, NiSOD has
      evolved a similar strategy for controlling the access of anions to the active
      site.

PMID- 19183071
TI  - The 2001 STRICTA recommendations for reporting acupuncture research: a review
      with implications for improving controlled clinical trial design.
AB  - BACKGROUND: The Consolidated Standards of Reporting Trials (CONSORT) guidelines
      were developed in 1996 by researchers and journal editors to improve the quality
      of reporting of biomedical research by providing a standardized format for
      researchers to present information on randomized controlled clinical trials
      (RCTs). This improved data reporting allows readers to independently assess the
      quality and conclusions of these studies, and has been widely incorporated in
      contemporary research reports. In 2001, a supplemental set of criteria that
      specifically address the reporting of design and implementation issues for RCTs
      involving the use of acupuncture was introduced, termed the STRICTA (Standards
      for Reporting Interventions in Controlled Trials of Acupuncture)
      recommendations.The CONSORT guidelines are stated to be part of a broader effort
      to improve the quality of research, as they can be used by researchers to
      optimize the design of future trials. Similarly, the STRICTA recommendations
      outline research reporting standards that are and should be considered when
      designing controlled clinical trials that involve the use of acupuncture. The
      CONSORT and STRICTA recommendations thus not only serve to improve research
      reporting, but also serve to provide guidance for optimizing the designs of
      future clinical trials. OBJECTIVES: This paper presents a review of the STRICTA
      recommendations for reporting the results of controlled trials utilizing
      acupuncture, discusses their potential limitations, and offers suggestions for
      additions/enhancements to those standards based on research issued subsequent to
      the issuance of the STRICTA recommendations in 2001.

PMID- 19183074
TI  - Mechanisms and significance of progenitor cell reduction in the metabolic
      syndrome.
AB  - Bone marrow-derived progenitor cells are involved in the homeostasis of the
      cardiovascular system through differentiation into endothelium, smooth muscle,
      and cardiomyocytes. Alterations of these extremely plastic cells have been
      recognized as both markers of cardiovascular risk and pathophysiological links
      between risk factors and development of atherosclerosis. Metabolic syndrome, as a
      cluster of well-defined cardiovascular risk factors, represents a strong
      predictor of cardiovascular events and death. Moreover, components of the
      syndrome interact with one another and synergistically increase this risk. Here
      we describe all metabolic syndrome components as being characterized by
      alterations in circulating progenitor cells, especially endothelial cells. We
      also highlight how endothelial progenitors may mediate the interactions between
      cardiometabolic risk factors in a complex interplay and discuss potential
      implications for prevention and therapy.

PMID- 19183073
TI  - Jupiter to Earth: CRP promotes atherothrombosis.

PMID- 19183077
TI  - Tenofovir-associated nephrotoxicity in two HIV-infected adolescent males.
AB  - We report two cases of tenofovir (TDF)-associated nephrotoxicity in perinatally
      HIV-infected adolescents. The first case, a 16-year-old African American male
      with an absolute CD4+ cell count of 314 cells/mm(3), presented with an abrupt
      rise in serum creatinine leading to irreversible renal failure while on TDF
      containing highly active antiretroviral therapy (HAART). While the patient had
      evidence of underlying kidney disease, the timing of his renal failure indicates
      that TDF played a central role. The second case, a 16-year-old African-American
      male with an absolute CD4+ cell count of 895 cells/mm3, presented with rickets
      and hypophosphatemia while receiving TDF-based HAART. To our knowledge, these
      cases represent the first reports of TDF-associated irreversible renal failure
      and rickets in pediatric patients. We believe these cases highlight important and
      potentially irreversible side effects of this agent and emphasize the need for
      further studies of the renal safety of TDF in pediatric patients.

PMID- 19183078
TI  - HIV knowledge and attitudes toward HIV testing of South Side Chicago Housing
      Authority residents.
AB  - High HIV infection rates in the United States are increasingly due to
      heterosexual risk behaviors, with increased rates in blacks and women. A survey
      of HIV knowledge and attitudes about HIV testing was conducted in an inner-city
      public housing population that included a convenience sample of residents of
      South Side Chicago Housing Authority facilities. The questionnaire addressed
      knowledge about HIV transmission and disease, health care options, condom use,
      prior HIV testing, and preferred places for HIV testing and education. Five
      hundred residents, ages 13-50 years completed the survey, during the period from
      November 2002 until April 2003. Eighty-three percent of the respondents were
      female and 50% of those surveyed were from 18-30 years of age. Race/ethnicity was
      not questioned in order to improve response rate. A comparable sample conducted
      earlier showed that population was 99% black race. Most respondents were
      knowledgeable about HIV transmission risk factors, although misinformation about
      transmission, treatment and prevention existed. Knowledge that HIV therapy is
      available was high (71%), while 25% thought an HIV vaccine was available and 13%
      thought there was a cure for HIV. Two thirds of sexually active respondents
      reported condom use in the past year. Three quarters reported previous testing
      for HIV and 90% of those tested returned for results. Most respondents wanted to
      learn more about HIV risk factors, testing and treatment but preferred primary
      care clinics to specialized places for HIV testing. Targeted HIV education
      interventions in the public housing facilities or primary care clinics are
      warranted.

PMID- 19183079
TI  - Rate and predictors of self-chosen drug discontinuations in highly active
      antiretroviral therapy-treated HIV-positive individuals.
AB  - Despite the clinical benefits of highly active antiretroviral therapy (HAART),
      sustained treatment remains a great challenge for HIV-infected people. The rate,
      consequences, and correlates of self-elected treatment interruptions (TI) are not
      known. The objectives of the study were to assess the rate of patient-elected TI
      in a cohort of HIV-infected people taking HAART, to evaluate whether patient
      elected TI is correlated with suboptimal nonadherence, and to identify the
      predictors of self-chosen HAART interruptions. Using a Web-based cross-sectional
      survey beginning in January 2006 primary outcomes were: (1) reports of having
      asked their physician to interrupt the current regimen (AskDisc) and (2) reports
      of at least one interruption of a minimum of 1 day of any of the drugs included
      in the regimen (INTERR). Three hundred fifty-nine people were enrolled; 296 were
      taking HAART. Twenty-three percent self-reported suboptimal adherence, 45%
      reported AskDisc, and 25% INTERR. Forty percent of people reporting INTERR self
      reported suboptimal adherence. As expected, AskDisc and INTERR were correlated
      with suboptimal adherence. The AskDisc group had higher CD4 cell counts and HIV
      RNA, more symptoms, and took more convenient regimens. The INTERR group had
      higher HIV RNA, were more likely to smoke, seek more information on HIV/AIDS, and
      less likely to take non-nucleoside reverse transcriptase inhibitors (NNRTIs). The
      rate of self-chosen TI was high and often related to suboptimal adherence. These
      findings may help clinicians to better monitor patients, and identify patients
      for targeted counseling.

PMID- 19183083
TI  - The controversy on screening for intimate partner violence: a question of
      semantics?
AB  - In this paper, we review the basis of the U.S. Preventive Services Task Force's
      recommendations related to routine screening for intimate partner violence (IPV),
      focus on two of the arguments of those who have rejected these recommendations,
      and based on these, suggest that this controversy has occurred, in part, as a
      result of different interpretations of the meaning of "screening." We
      differentiate screening from situations in which asking about IPV is essential
      for differential diagnosis, that is, exploring exposure to IPV when there are
      signs and symptoms that might result from this exposure. Finally, we describe the
      randomized, controlled trial CDC is conducting to contribute to the evidence the
      U.S. Preventive Services Task Force requries to make its recommendations.

PMID- 19183084
TI  - Toward optimal health: diagnosis and management of disordered sleep in women: Dr.
      Daniel J Buysse interviewd by Jodi R. Godfrey.

PMID- 19183085
TI  - AMWA position statement: cervical cancer prevention.

PMID- 19183086
TI  - Left ventricular dysfunction secondary to ischemia in women with angina and
      normal coronary angiograms.
AB  - BACKGROUND: Microvascular disease is proposed as a cause of segmental myocardial
      blood flow abnormalities and heterogeneous myocardial perfusion in cardiac
      syndrome X. OBJECTIVE: To assess if myocardial ischemia can be evidenced through
      both perfusion abnormalities and poststress left ventricular ejection fraction
      (LVEF) reduction by gated single photon emission tomography (SPECT) myocardial
      scintigraphy in women with syndrome X in a similar way to those with epicardial
      coronary lesions. METHODS: Three groups of postmenopausal women were studied:
      group I, 20 women with angina, perfusion defects, and normal coronary
      angiography; group II, 20 women with epicardial coronary lesions (> or =50% of
      coronary lumen reduction); group III, 15 volunteers without signs or symptoms of
      ischemia (control group). Each underwent technetium-99m ((99m)TC)
      methoxyisobutylisonitrile gated SPECT myocardial scintigraphy (protocol: exercise
      stress-rest), brachial artery endothelial function measured by ultrasonography,
      and lipidogram. RESULTS: Groups I and III patients had a higher body mass index
      (BMI). There were more smokers in groups I and II. Very low density lipoprotein
      cholesterol (VLDL-C) and triglycerides were higher in group II patients. The
      brachial artery vasodilator responsiveness after 5 minutes of ischemia was
      similarly lower in patients of groups I and II compared with those of group III
      (3% vs. 6.5%, respectively; p = 0.03 group III vs. group I and group II). Mean
      DeltaLVEF (LVEF poststress minus LVEF at rest) was -3.86%, -2.90%, and 4.18% in
      groups I, II, and III, respectively (p = NS between I and II, p = 0.005 between
      II and III, and p = 0.003 between I and III). In 43% of group I patients and in
      10 of 18 group III patients with perfusion defects, there was a poststress LVEF
      reduction >5%. CONCLUSIONS: Stress-induced ischemia is associated with poststress
      LVEF reduction as a probable manifestation of myocardial stunning in
      postmenopausal women with typical angina and normal coronary angiography.

PMID- 19183087
TI  - Self-management, amitriptyline, and amitripyline plus triamcinolone in the
      management of vulvodynia.
AB  - OBJECTIVE: To conduct a prospective study to determine the efficacy of self
      management interventions, amitriptyline, and amitriptyline plus topical
      triamcinolone in reducing vulvar pain in women with vulvodynia. METHODS: This was
      a randomized, prospective study of 53 women between the ages of 18 and 72 with
      vulvodynia. Participants undertook one of three treatment interventions for a
      period of 12 weeks: self-management, oral amitriptyline (10-20 mg/day), or
      topical triamcinolone plus oral amitriptyline (10-20 mg/day). The McGill Pain
      Questionnaire (MPQ) was used to measure changes in qualitative pain using the
      pain rating index (PRI) and in quantitative pain using the present pain intensity
      (PPI) scale. RESULTS: Of the 53 randomized subjects, 43 completed the trial.
      There were no statistically significant differences in PRI or PPI scores among
      the three treatment groups. Significant within-group differences were observed in
      the self-management group on the PRI and in the amitriptyline group on the PPI.
      CONCLUSIONS: This first randomized, prospective trial suggests that self
      management has a modest effect and that low-dose amitriptyline (with and without
      topical triamcinolone) is not effective in reducing pain in women with
      vulvodynia.

PMID- 19183088
TI  - Lifetime exposure to family violence: implications for the health status of older
      African American women.
AB  - BACKGROUND: Family violence among older women encompasses intimate partner
      violence (IPV) and elder maltreatment, both linked to poor health status. Little
      is known about the association between family violence and the health status of
      older innercity African American women. METHODS: One hundred fifty-eight African
      American women, aged >/=50, were interviewed in the ambulatory clinics of a large
      public hospital. Lifetime family violence exposure as an adult was measured by
      the Family Violence against Older Women (FVOW) scale; physical and mental health
      status were measured by the physical and mental component summary scores of the
      Short Form 8 scale. RESULTS: Mean participant age was 61.5 years (SD 7.1).
      Participants with FVOW scores in the top quartile were considered to have high
      lifetime family violence exposure. Participants with higher family violence
      exposure and those younger, unemployed, or disabled reported worse physical and
      mental health status. Lower income and not having Medicare were associated with
      worse physical and mental health status, respectively. Using stepwise linear
      regression techniques, only employment status and high family violence exposure
      were associated with worse physical (F = 7.16, p = 0.0011) and mental health (f =
      7.09, p = 0.0012) status. Women with high FVOW scores reported physical and
      mental component summary scores that were 4.18 and 4.6 points lower,
      respectively, than those of women with lower FVOW scores. CONCLUSIONS: Among
      older, innercity, African American women, lack of employment and high levels of
      family violence exposure as an adult are associated with worse physical and
      mental health status. Clinicians caring for older African American women need to
      be cognizant of the role both current and prior violence exposure may play in
      their patients' current health status.

PMID- 19183089
TI  - Sexual orientation and intentions to obtain breast cancer screening.
AB  - AIMS: This longitudinal study examined predictors of intentions to obtain breast
      cancer screening in two samples, one comprising self-identified lesbian/bisexual
      women (n = 150) and the other comprising heterosexual women (n = 400). We
      hypothesized that beliefs about mammography, cancer vulnerability, and attitudes
      toward the medical provider would mediate the relationship between sexual
      orientation and plans to obtain breast cancer screening. METHODS: Women in this
      study participated in one of two larger clinical trials of breast cancer risk
      counseling methods. All participants completed questionnaires about breast cancer
      screening attitudes at baseline and at a 6-month follow-up. RESULTS: Logistic
      regression analyses, controlling for age, education, and race, revealed that
      baseline negative beliefs about mammography, lower levels of provider trust, and
      less perceived risk of breast cancer significantly mediated the relationship
      between sexual orientation and 6-month intentions to obtain a clinical breast
      examination (CBE) and mammography. CONCLUSIONS: These findings suggest that
      attitudes and beliefs about breast cancer, breast cancer screening, and medical
      providers impact lesbian/bisexual women's willingness to plan for CBE and
      mammography.

PMID- 19183090
TI  - Physical activity participation among Caribbean Hispanic women living in New
      York: relation to education, income, and age.
AB  - BACKGROUND: Inadequate participation in physical activity is a serious public
      health issue in the United States, with significant disparities among population
      groups. In particular, there is a scarcity of information about physical activity
      among Caribbean Hispanics, a group on the rise. METHODS: Our goal was to
      accumulate data on physical activity among Caribbean Hispanic women living in New
      York and determine the relation between physical activity and age, marital
      status, education, income, primary language, and children in the household. To
      this end, a survey adapted from the National Health Interview Survey of the
      National Center for Health Statistics assessing type, frequency, and duration of
      physical activity was administered. RESULTS: There were 318 self-identified
      Hispanic women who participated. Total activity time, mean 385 +/- 26 minutes,
      and education (r = 0.14, p < 0.01) were significantly related. Women who had
      attended some college had greater total activity time than those with some high
      school education (p = 0.046) or < 8th grade education (p = 0.022). Walking as a
      form of transportation was the most frequent pursuit, 285 +/- 21 minutes. Age (r
      = -0.34, p < 0.001) and education (r = 0.25, p < 0.001) correlated with
      nonwalking activity time (leisure time). Nonwalking activity times were greater
      in younger, that is, 18-29 years (p < 0.001) and college-educated women (p <
      0.001). Physical activity recommendations were met by 11%; and 17% reported no
      physical activity. CONCLUSIONS: Among Caribbean Hispanic women living in New York
      City, the current recommendations for physical activity are met by 11%, and
      physical activity and education are significantly related. Our observation that
      education is a critical factor related to physical activity suggests that
      programs to address the promotion of a physically active lifestyle are needed.

PMID- 19183091
TI  - Language use and the receipt of cancer screening recommendations by immigrant
      Chinese American women.
AB  - BACKGROUND: Cancer screening rates are low among Chinese American women, a mostly
      immigrant minority population. This is possibly because they do not receive
      cancer screening recommendations from their physicians. The objective of this
      study was to determine if the rate at which physicians recommend cancer screening
      to older Chinese American women differs according to the language used during
      visits. METHODS: Data for the cross-sectional study were collected from a
      telephone survey of older Chinese American women residing in the Washington, DC,
      area. A total of 507 asymptomatic Chinese American women aged > or =50 who had a
      regular physician participated in this study. The main outcome was women's self
      reported perception of having received a recommendation from their physician for
      mammography, Pap tests, or colorectal cancer screening in the past 2 years. The
      main independent variable was the language used during visits (English vs.
      Chinese). Patient age, educational level, employment status, cultural views,
      physician specialty, physician gender, and length of relationship with the
      physician were included in the multiple logistic regression analyses. RESULTS:
      Chinese women who communicated with their physicians in English were 1.71 (95% CI
      1.00-2.96) and 1.73 (95% CI 1.00-3.00) times more likely to report having
      received mammography and colorectal cancer screening recommendations,
      respectively (p < 0.05). Physicians in family medicine or general practice were
      2.11 (95% CI 1.31-3.40) and 1.70 (95% CI 1.06-2.48) times more likely to
      recommend cancer screening than those in other specialties. CONCLUSIONS: Chinese
      American women who conversed with their physicians in Chinese were less likely to
      perceive receiving cancer screening recommendations. Future research is needed to
      identify physician-specific knowledge, attitude, and cultural barriers to
      recommending cancer screening.

PMID- 19183092
TI  - A multisite examination of sex differences in cardiac rehabilitation barriers by
      participation status.
AB  - BACKGROUND: Despite its proven benefits and need, women are significantly less
      likely than men to participate in and complete cardiac rehabilitation (CR). The
      purpose of this study was to quantitatively investigate sex differences in CR
      barriers by participation status. METHODS: Cardiac outpatients (1496, 430 female,
      28.7%) of 97 cardiologists completed a mailed survey to discern CR participation.
      Respondents were asked to rate 19 CR barriers on a 5-point Likert scale. RESULTS:
      Five hundred twenty-nine (43%) respondents self-reported participating in CR,
      with men being more likely to participate (p < 0.05). There was no significant
      sex difference in total number of CR barriers, but differences in individual
      barriers were found. For CR participants, t tests revealed significant sex
      differences in the perception of exercise as tiring or painful (p = 0.042) and
      work responsibilities (p = 0.013). For CR nonparticipants, women rated the
      following barriers as greater than men: transportation (p = 0.025), family
      responsibilities (p = 0.039), lack of CR awareness (p = 0.036), experiencing
      exercise as tiring or painful (p = 0.002), and comorbidities (p = 0.009).
      CONCLUSIONS: Overall, women do not perceive greater barriers to CR participation
      than men, but the nature of their barriers differs, particularly among
      nonparticipants. Beliefs about the value of CR, awareness, and exercise
      parameters are all modifiable barriers that should be addressed among women.

PMID- 19183093
TI  - The association between role overload and women's mental health.
AB  - OBJECTIVE: To determine the importance of role overload (the extent to which a
      person feels overwhelmed by her total responsibilities) relative to other known
      social determinants of women's mental health. METHODS: A Canadian national,
      random sample, cross-sectional telephone survey in 2003 assessed the association
      among role overload, types and quality of roles (parent, employee, spouse),
      sociodemographics, and mental health (using the SF-12) using linear regression.
      Analysis included 716 women aged 25-54 who indicated that their youngest child
      living in the household was aged < or =17 years. RESULTS: Perceptions of greater
      role overload were associated with poorer mental health (p < 0.0001). Women
      working <35 hours per week (p = 0.04) or 35-40 hours per week (p 5 0.002)
      reported better mental health than nonemployed women, as did women with the
      highest annual household income ($70,000+)(p = 0.001). Also associated with
      better mental health were higher marital status quality scores for both married
      and single women (p < 0.001), higher job quality scores among employed women (p =
      0.02), greater homemaking quality scores among unemployed women (p = 0.03), and
      women reporting high parental quality (p = 0.04) CONCLUSIONS: Role overload
      showed a stronger relationship to mental health than other sociodemographic
      variables, including income. Our findings indicate the importance of measuring
      women's experience of their multiple roles rather than focusing on single roles.
      More research is warranted on the totality of women's experiences of their many
      social role obligations.

PMID- 19183094
TI  - Effects of information framing on human papillomavirus vaccination.
AB  - BACKGROUND: In June 2006, the first vaccine to prevent human papillomavirus (HPV)
      transmission was approved for use in females in the United States. Because the
      vaccine was approved for females as young as 9, its success depends on parents'
      and individuals' willingness to accept vaccination. Little is known about how
      attitudes toward this vaccine will be influenced by the way the vaccine is
      portrayed in the media or in public debate. METHODS: To assess the effects of
      information framing on intentions to vaccinate self or female children, if
      appropriate, 635 adults read one of three short descriptive paragraphs about the
      vaccine, each of which emphasized a different aspect of the vaccine. Participants
      were then asked about their intentions to vaccinate under cost or no-cost
      conditions. RESULTS: Women who read that the vaccine protects only against
      cervical cancer had significantly higher intentions to vaccinate themselves when
      the vaccine was available at little or no cost compared with women who read
      alternate versions of the descriptive paragraph, F(2,325) = 5.74, p = 0.004.
      CONCLUSIONS: How the HPV vaccine is framed may affect vaccination intentions
      under certain conditions. Women may be more receptive to the vaccine if it is
      framed as a cervical cancer prevention tool rather than a sexually transmitted
      infection (STI) prevention tool.

PMID- 19183095
TI  - Beliefs of women's risk as research subjects: a four-city study examining
      differences by sex and by race/ethnicity.
AB  - BACKGROUND: Given the history of vulnerability of women of childbearing age to
      medical treatments that have caused injury, for example, diethylstilbestrol (DES)
      and thalidomide, it is surprising that, to date, little research has directly
      examined attitudes of the general public regarding the vulnerability of women
      when they participate in biomedical research studies. METHODS: We asked three
      questions about beliefs of women as biomedical research subjects of 623 white,
      353 black, and 157 Hispanic people in four U.S. cities: (1) Do you believe that
      women are more likely to be "taken advantage of" when they become subjects in a
      medical research project as compared to men? (2) Do you believe that women of
      childbearing age (15-45-year-olds) should become study participants in medical
      research projects? and, if the response was no or don't know/not sure, (3) Would
      you still say no or don't know/not sure to question 2 even if it meant that we
      would not know anything about the health and medical treatments for women aged 15
      45 years? RESULTS: Overall, women were 60% more likely than men to state that
      women were more likely than men to be "taken advantage of," even when controlling
      for potential confounders, and both black and Hispanic participants were much
      more likely than white participants to state that this was the case. The majority
      of respondents (57.4%) said that women of childbearing age should not be research
      subjects; among women, both black and Hispanic people were less likely than white
      people to change their minds when prompted that this might mean that "nothing
      would be known about the health and medical treatments for women aged 15-45
      years." CONCLUSIONS: A substantial proportion of the participants reported
      knowledge of historical events, and this knowledge was related, particularly in
      black participants, to attitudes toward vulnerability of women as biomedical
      research subjects.

PMID- 19183096
TI  - Measurement of maternal perceptions of support and control in birth (SCIB).
AB  - BACKGROUND: High control and support during labor are associated with improved
      birth outcomes and increased maternal satisfaction with the birth experience, but
      measures of control and support are varied and often unidimensional. This paper
      reports the development and validation of a questionnaire measure of support and
      control in birth for use in research on birth experience and outcomes. METHODS:
      Study 1 interviewed women after birth (n = 10) to identify important dimensions
      of control and support. In study 2 (n = 402), the Support and Control in Birth
      (SCIB) questionnaire was developed, with three dimensions of internal control,
      external control, and support, which was completed by women who had given birth.
      RESULTS: Principal components analysis identified a 33-item, three-component
      solution, which accounted for 55% of the variance and had good reliability
      (Cronbach's alpha 0.86-0.93). CONCLUSIONS: Overall, these studies suggest the
      SCIB provides a reliable and comprehensive measure of support and control in
      birth.

PMID- 19183099
TI  - Delivery of a live newborn in a triplet pregnancy complicated by preeclampsia
      after intrauterine demise of two and expulsion of one triplet: a case report.
AB  - Delayed interval delivery in twin pregnancies is an unusual occurrence, even more
      so in triplet pregnancies. We report on a delayed interval delivery in a
      dichorionic triamniotic triplet pregnancy after in vitro fertilization (IVF).
      Because of severe twin to twin transfusion syndrome (TTTS), two fetuses demised
      at 22 weeks of gestation. One of the two fetuses spontaneously aborted at 25
      weeks of gestation. The remaining live fetus and the second demised fetus were
      delivered by cesarean section 9 weeks later because of the occurrence of
      preeclampsia. This case indicates that delayed interval delivery in triplets is
      possible and that preeclampsia can occur after intrauterine demise of two
      fetuses.

PMID- 19183097
TI  - Increased strength and physical performance with eccentric training in women with
      impaired glucose tolerance: a pilot study.
AB  - BACKGROUND: Menopause is associated with both a loss of muscle mass and a
      worsening of insulin sensitivity (IS). Although eccentric resistance exercise
      (ECC) can effectively improve muscle mass over time, a single bout of ECC can
      worsen IS. This study assessed the effect of repeated ECC on IS, muscle mass, and
      function in postmenopausal women with impaired glucose tolerance (IGT). METHODS:
      Sixteen PM women (aged 56 years +/- 6.4) with IGT were randomly assigned to a 12
      week, knee extensor ECC program (n = 10) or a nonexercise control group (CON) (n
      = 6). Participants underwent hyperinsulinemic-euglycemic clamps, dual-energy x
      ray (DEXA) absorptiometry, quadriceps strength assessment, 6-minute walk (6MW)
      tests, and an assessment of steps taken per day before and after training.
      RESULTS: ECC participants experienced greater increases in leg lean soft tissue
      mass (ECC, 0.41 kg; CON, -0.53 kg; p = 0.03), quadriceps strength (ECC, 9.3 kg
      force; CON, -2.9 kg force; p = 0.02), and 6MW distance (ECC, 56.4 meters; CON,
      3.3 meters; p = 0.03) than CON participants and demonstrated a trend toward more
      steps taken per day posttraining (ECC, +1747 steps; CON, +339 steps; p = 0.10).
      IS was unchanged. CONCLUSIONS: This novel exercise improves muscle mass and
      function without worsening IS in postmenopausal women with IGT. Because it can be
      performed at low levels of exertion and improves muscle mass and function without
      impairing IS, ECC should be used to ameliorate muscle loss in physically inactive
      postmenopausal women. The impact of longer-term ECC on IS should be investigated.
      Demonstrating that ECC does not worsen IS in this population is significant
      because it has promise to combat the muscle-mediated impairments common in aging
      women.

PMID- 19183100
TI  - Why do faculty leave? Reasons for attrition of women and minority faculty from a
      medical school: four-year results.

PMID- 19183098
TI  - Medical conditions and symptoms associated with posttraumatic stress disorder in
      low-income urban women.
AB  - BACKGROUND: Epidemiological studies have consistently reported rates of
      posttraumatic stress disorder (PTSD) in women that are twice that of men. In men
      and women, PTSD has been associated with comorbid medical conditions, medical
      symptoms and lower self-rating of health. In low-income urban women, rates of
      PTSD are even more elevated than in suburban women and may be related to observed
      health disparities. METHODS: In this study, 250 women seeking healthcare at an
      urban clinic were interviewed for a PTSD diagnosis, major depressive disorder
      (MDD), the experience of traumatic events, the experience of current and past
      common medical conditions and symptoms, and subjective rating of health. A chart
      review was used to assess healthcare use in the past year. RESULTS: More current
      (5.2 vs. 3.8, p < 0.05) and past medical conditions (4.6 vs. 3.3, p < 0.05) were
      reported by women with a lifetime history of PTSD than by women without this
      history, after controlling for demographics and current depression. Women with
      lifetime PTSD also had more annual clinic appointments (5.9 vs. 3.8 p < 0.03) and
      were 2.4 times (p < 0.05) more likely to report lower appraisal of their physical
      health. CONCLUSIONS: These findings suggest that urban health-seeking women with
      PTSD experience health impairments that may cause increased morbidity and that
      healthcare providers should consider the health ramifications of PTSD when
      providing medical care to women.

PMID- 19183102
TI  - Biological basis of bone formation, remodeling, and repair-part II: extracellular
      matrix.
AB  - The bony biochemical environment is a complex system that permits and promotes
      cellular functions that lead to matrix production and ossification. In Part I of
      this review, we discussed the important actions of signaling molecules, including
      hormones, cytokines, and growth factors. Here, we review other constituents of
      the extracellular matrix, including minerals, fibrinous and nonfibrinous
      proteins, and enzymes such as the matrix metalloproteinases. We conclude with a
      discussion of the role of biochemical modulation in endogenous and exogenous
      tissue engineering.

PMID- 19183103
TI  - BCS in drug discovery, development, and regulation.

PMID- 19183105
TI  - Toward an increased understanding of the barriers to colonic drug absorption in
      humans: implications for early controlled release candidate assessment.
AB  - The purpose of this study was to increase the understanding of in vivo colonic
      drug absorption in humans by summarizing and evaluating all regional in vivo
      human absorption data with focus on the interpretation of the colonic absorption
      data in relation to intestinal permeability and solubility. In addition, the
      usefulness of the Biopharmaceutics Classification System (BCS) in early
      assessment of the in vivo colonic absorption potential of controlled release drug
      candidates was investigated. Clinical regional absorption data (Cmax, Tmax, and
      AUC) of 42 drugs were collected from journal articles, abstracts, and internal
      reports, and the relative bioavailability in the colon (Frel(colon)) was obtained
      directly or calculated. Bioavailability, fraction dose absorbed, and information
      if the compounds were substrates for P-glycoprotein (P-gp) or cytochrome P450 3A
      (CYP3A) were also obtained. The BCS I drugs were well absorbed in the colon
      (Frel(colon) > 70%), although some drugs had lower values due to bacterial
      degradation in the colon. The low permeability drugs (BCS III/IV) had a lower
      degree of absorption in the colon (Frel(colon) < 50%). There was a clear
      correlation between in vitro Caco-2 permeability and Frel(colon), and atenolol
      and metoprolol may function as permeability markers for low and high colonic
      absorption, respectively. No obvious effect of P-gp on the colonic absorption of
      the drugs in this study was detected. There was insufficient data available to
      fully assess the impact of low solubility and slow dissolution rate. The
      estimated in vivo fractions dissolved of the only two compounds administered to
      the colon as both a solution and as solid particles were 55% and 92%,
      respectively. In conclusion, permeability and solubility are important barriers
      to colonic absorption in humans, and in vitro testing of these properties is
      recommended in early assessment of colonic absorption potential.

PMID- 19183104
TI  - Toward an in vivo dissolution methodology: a comparison of phosphate and
      bicarbonate buffers.
AB  - The purpose of this research was to evaluate the difference between the
      pharmaceutical phosphate buffers and the gastrointestinal bicarbonates in
      dissolution of ketoprofen and indomethacin, to illustrate the dependence of
      buffer differential on biopharmaceutical properties of BCS II weak acids, and to
      recommend phosphate buffers equivalent to bicarbonates. The intrinsic dissolution
      rates of ketoprofen and indomethacin were experimentally measured using a
      rotating disk method at 37 degrees C in USP SIF/FaSSIF and various concentrations
      of bicarbonates. Theoretical models including an improved reaction plane model
      and a film model were applied to estimate the surrogate phosphate buffers
      equivalent to the bicarbonates. Experimental results show that the intrinsic
      dissolution rates of ketoprofen and indomethacin in USP and FaSSIF phosphate
      buffers are 1.5-3.0 times that in the 15 mM bicarbonates. Theoretical analysis
      demonstrates that the buffer differential is largely dependent on the drug pK(a)
      and second on solubility, and weakly dependent on the drug diffusivity. Further,
      in accordance with the drug pK(a), solubility and diffusivity, a simple phosphate
      surrogate was proposed to match an average bicarbonate value (15 mM) of the upper
      gastrointestinal region. Specifically, phosphate buffers of 13-15 mM and 3-4 mM
      were recommended for ketoprofen and indomethacin, respectively. For both
      ketoprofen and indomethacin, the intrinsic dissolution using the phosphate
      surrogate buffers closely approximated the 15 mM bicarbonate buffer. This work
      demonstrates the substantial difference between pharmaceutical phosphates and
      physiological bicarbonates in determining the drug intrinsic dissolution rates of
      BCS II weak acids, such as ketoprofen and indomethacin. Surrogate phosphates were
      recommended in order to closely reflect the in vivo dissolution of ketoprofen and
      indomethacin in gastrointestinal bicarbonates, which has significant implications
      for defining buffer systems for BCS II weak acids in developing in vitro
      bioequivalence dissolution methodology.

PMID- 19183106
TI  - Activation of the nuclear receptor PXR decreases plasma LDL-cholesterol levels
      and induces hepatic steatosis in LDL receptor knockout mice.
AB  - To investigate the potential for pregnane X receptor (PXR) ligands as
      antiatherosclerotic drugs, we have determined the effect of PXR activation on
      lipid metabolism in an established atherosclerotic mouse model. LDL receptor
      knockout mice were treated with the PXR agonist PCN. PCN induced a striking 66%
      decrease in plasma LDL-cholesterol levels. PCN did not affect the cholesterol
      levels of high-density lipoprotein (HDL) or very-low-density lipoprotein (VLDL).
      VLDL-triglyceride levels were 2.2-fold increased by PCN, resulting in the
      presence of triglyceride-rich VLDL particles. This coincided with a 60% decreased
      hepatic lipase (HL)-mediated plasma lipolysis rate, which could be attributed to
      a decrease in the hepatic mRNA expression level of both HL (-31%) and its
      cofactor apolipoprotein A4 (-62%). In the liver, PCN induced a significant
      increase in the level of triglycerides (+65%) and phospholipids (+72%), a
      hallmark of hepatic steatosis, leading to a marked increase in Oil red O neutral
      lipid staining. A similar effect was noticed in ApoE knockout mice. Our studies
      show that activation of the nuclear receptor PXR by PCN leads to an inhibition of
      the plasma HL-mediated lipolysis rate, which is associated with a decrease in
      plasma LDL-cholesterol levels and induction of hepatic steatosis in LDL receptor
      knockout mice.

PMID- 19183108
TI  - Ethical issues of cardiopulmonary resuscitation: comparison of emergency
      physician practices from 1995 to 2007.
AB  - OBJECTIVES: The objectives were to determine current practice among emergency
      physicians (EPs) regarding the initiation and termination of cardiopulmonary
      resuscitative (CPR) efforts and to compare responses to those from a similar
      study performed in 1996. METHODS: This anonymous self-administered survey was
      mailed to 4,991 randomly selected EPs. Main outcome measures included responses
      regarding current practices related to advance directives and initiation and
      termination of resuscitative attempts. Results from 1995 and 2007 surveys were
      compared, using 95% confidence intervals (CIs) of the difference between groups.
      RESULTS: Among 928 respondents (18% response rate), most (86%) honor legal
      advance directives, an increase over 78% reported in 1996 (8% increase, 95% CI =
      5% to 11%). Few honor unofficial documents (7%) or verbal reports (12%) of
      advance directives. Many (58%) make decisions regarding resuscitation because of
      fear of litigation or criticism. Most respondents (62%) attempt resuscitation in
      10% or more of cases of cardiac arrest. A majority (56%) have attempted more than
      10 resuscitations in the past 3 years, despite expectations that such efforts
      would be futile. Factors reported to be "very important" in making resuscitation
      decisions were advance directives (78%), witnessed arrest (77%), downtime (73%),
      family wishes (40%), presenting rhythm (38%), age (28%), and prearrest state of
      health (25%). A significant majority of respondents (80%) indicated that ideally,
      legal concerns should not influence physician practices regarding resuscitation,
      but that in the current environment, legal concerns do influence practice (92%).
      Other than the increase in respondents who honor legal advance directives, these
      results do not differ substantially from responses in 1996. CONCLUSIONS: Most EPs
      attempt to resuscitate patients in cardiopulmonary arrest regardless of poor
      outcomes, except in cases where a legal advance directive is available. Many EPs'
      decisions regarding resuscitation are based on concerns of litigation and
      criticism, rather than professional judgment of medical benefit. Most results did
      not differ significantly from the previous study of 1995, although more
      physicians honor legal advance directives than previously noted.

PMID- 19183109
TI  - Occult bacteremia in the post-pneumococcal conjugate vaccine era: does the blood
      culture stop here?

PMID- 19183107
TI  - Transferrin receptor-targeted lipid nanoparticles for delivery of an antisense
      oligodeoxyribonucleotide against Bcl-2.
AB  - Antisense oligonucleotide G3139-mediated down-regulation of Bcl-2 is a potential
      strategy for overcoming chemoresistance in leukemia. However, the limited
      efficacy shown in recent clinical trials calls attention to the need for further
      development of novel and more efficient delivery systems. In order to address
      this issue, transferrin receptor (TfR)-targeted, protamine-containing lipid
      nanoparticles (Tf-LNs) were synthesized as delivery vehicles for G3139. The LNs
      were produced by an ethanol dilution method, and lipid-conjugated Tf ligand was
      then incorporated by a postinsertion method. The resulting Tf-LNs had a mean
      particle diameter of approximately 90 nm and G3139 loading efficiency of 90.4%.
      Antisense delivery efficiency of Tf-LNs was evaluated in K562, MV4-11, and Raji
      leukemia cell lines. The results showed that Tf-LNs were more effective than
      nontargeted LNs and free G3139 (p < 0.05) in decreasing Bcl-2 expression (by up
      to 62% at the mRNA level in K562 cells) and in inducing caspase-dependent
      apoptosis. In addition, Bcl-2 down-regulation and apoptosis induced by Tf-LN
      G3139 were shown to be blocked by excess free Tf and thus were TfR-dependent.
      Cell lines with higher TfR expression also showed greater Bcl-2 down-regulation.
      Furthermore, up-regulation of TfR expression in leukemia cells by iron chelator
      deferoxamine resulted in a further increase in antisense effect (up to 79% Bcl-2
      reduction in K562 at the mRNA level) and in caspase-dependent apoptosis (by
      approximately 3-fold) by Tf-LN. Tf-LN-mediated delivery combined with TfR up
      regulation by deferoxamine appears to be a potentially promising strategy for
      enhancing the delivery efficiency and therapeutic efficacy of antisense
      oligonucleotides.

PMID- 19183112
TI  - Essential E mergency Procedures.

PMID- 19183113
TI  - Single transpulmonary thermodilution and continuous monitoring of central venous
      oxygen saturation during off-pump coronary surgery.
AB  - BACKGROUND: Off-pump coronary artery bypass grafting (OPCAB) requires thorough
      monitoring of hemodynamics and oxygen transport. Our aim was to find out whether
      therapeutic guidance during and after OPCAB, using an algorithm based on advanced
      monitoring, influences perioperative hemodynamic and fluid management as well as
      the length of post-operative ICU and hospital stay. METHODS: Patients were
      randomized into two groups of hemodynamic monitoring: the conventional monitoring
      (CM) group (n=20) and the advanced monitoring (AM) group (n=20). In the CM group,
      therapy was guided by central venous pressure, mean arterial pressure (MAP) and
      heart rate (HR), and in the AM group by the intrathoracic blood volume index,
      MAP, HR, central venous oxygen saturation (ScvO(2)) and cardiac index (CI). The
      measurements were performed before and during surgery, and at 2, 4 and 6 h post
      operatively. RESULTS: In the AM group, colloids and dobutamine were given more
      frequently and were accompanied by increments in ScvO(2), CI and oxygen delivery
      compared with baseline. The percentage of ephedrine administration was higher in
      the CM group. The algorithm guided by AM decreased time until achieving the
      status of 'fit for ICU discharge' and post-operative hospital stay by 15% and
      25%, respectively. CONCLUSIONS: A goal-directed algorithm based on advanced
      hemodynamic monitoring and continuous measurement of ScvO(2) facilitates early
      detection and correction of hemodynamic changes and influences the strategy for
      fluid therapy that can improve the course of post-operative period after coronary
      artery bypass grafting on the beating heart.

PMID- 19183114
TI  - Allergy in day care children: prevalence and environmental risk factors.
AB  - AIM: To investigate the prevalence of atopic disease among Finnish day care
      children and the relationship between atopy and environmental factors. METHODS: A
      cross-sectional study of 594 day care children aged 1-6 years from Helsinki,
      Finland. Each child's history of atopic diseases and environmental exposure was
      collected in a questionnaire completed by the parents. RESULTS: The prevalence of
      diagnosed asthma was 0.9% for the 1-3-year olds and 5.5% for the 4-6-year olds,
      atopic eczema/dermatis was 16% in both groups, and allergic rhinitis 5% in the
      younger group, 9% in the older group. According to multivariable logistic
      regression models, breastfeeding (exclusive > or =4 months or partial > or =6
      months) reduced the risk of atopic diseases (OR = 0.60; CI(95) 0.39-0.93, p =
      0.021). Atopic diseases were more common in the oldest age group, 5-6-year olds,
      compared to the youngest, 1-2-year olds (OR = 2.18; CI(95) 1.14-4.15, p = 0.018).
      One parent with atopic disease increased the child's risk (OR = 1.89; CI(95) 1.20
      2.97, p = 0.006), more so if both parents had a history (OR = 3.17; CI(95) 1.48
      6.78, p = 0.003). CONCLUSION: Our results support the hypothesis that
      breastfeeding for at least six months may protect against atopic diseases. The
      child's greater age (5-6 years) and parental history of atopic diseases increased
      the risk of atopy.

PMID- 19183115
TI  - Flaws in the assessment of the best interests of the newborn.
AB  - We examined the literature on ethical decisions regarding neonates, to assess
      whether personal beliefs and prejudices influence end-of-life decisions taken by
      caregivers. Studies show that religion and familiarity with disability influence
      caregivers' decisions, whereas the influx of already being a parent, age, sex and
      professional experience is controverse. Caregivers' attitudes towards end-of-life
      decisions are also affected by personal concerns about litigation, prejudices and
      their view of disability. The concept of 'poor quality of life' is widely used as
      a reference in end-of-life decisions, but this can be interpreted differently,
      leaving room for a wide range of personal viewpoints. In most cases, parents'
      opinions are considered important and are sometimes the main determinant in
      decision making. However, it is unclear whether parents' decisions are based on
      their own wishes or on the best interests of the newborn. CONCLUSION: In neonatal
      end-of-life decisions, patients may not receive cures based only on their best
      interests.

PMID- 19183116
TI  - Agrichemicals in surface water and birth defects in the United States.
AB  - OBJECTIVES: To investigate if live births conceived in months when surface water
      agrichemicals are highest are at greater risk for birth defects. METHODS: Monthly
      concentrations during 1996-2002 of nitrates, atrazine and other pesticides were
      calculated using United States Geological Survey's National Water Quality
      Assessment data. Monthly United States birth defect rates were calculated for
      live births from 1996 to 2002 using United States Centers for Disease Control and
      Prevention natality data sets. Birth defect rates by month of last menstrual
      period (LMP) were then compared to pesticide/nitrate means using logistical
      regression models. RESULTS: Mean concentrations of agrichemicals were highest in
      April-July. Total birth defects, and eleven of 22 birth defect subcategories,
      were more likely to occur in live births with LMPs between April and July. A
      significant association was found between the season of elevated agrichemicals
      and birth defects. CONCLUSION: Elevated concentrations of agrichemicals in
      surface water in April-July coincided with higher risk of birth defects in live
      births with LMPs April-July. While a causal link between agrichemicals and birth
      defects cannot be proven from this study an association might provide clues to
      common factors shared by both variables.

PMID- 19183117
TI  - Vagal bradycardia at term.
AB  - We discuss the case of a newborn boy presenting well into term with severe
      bradycardic events and sinus pauses up to 5.4 sec. Sinus bradycardia below 80 bpm
      and sinus pauses or asystole of more than 2 sec are considered pathologic at
      term. After exclusion of specific causes, the diagnosis of vagal hyper
      reflectivity (VHR) was retained, a state caused by unbalance between sympathetic
      and parasympathetic activity, the latter overriding the former. It is thought to
      be a functional and transitional anomaly of the sympathetic and vagal tone during
      the first months of life and may lead to prolonged monitoring and delayed
      hospital discharge. This form of rare bradycardia can be treated with atropine
      and allowed in our case immediate resolution of events and safe discharge from
      hospital. CONCLUSION: When VHR is diagnosed, atropine is the treatment permitting
      resolution of symptomatic episodes of bradycardia and early and safe discharge
      from hospital.

PMID- 19183118
TI  - High prevalence of cardio-metabolic risk factors among adolescents with
      intellectual disability.
AB  - Adults with intellectual disabilities (IDs) have poor lifestyle-related health
      compared with the general population. Our aim was to study whether such
      differences are present already in adolescents. AIM: To compare the prevalence
      and severity of cardio-metabolic risk factors and cardio-vascular fitness in
      adolescents with and without IDs. METHODS: Intellectual disability (ID) students
      (n = 66) and non-intellectual disability (non-ID) students from practical (non-ID
      p) (n = 34) and theoretical (non-ID-t) (n = 56) programmes were recruited from
      three upper secondary schools. Anthropometric data, blood pressure, body
      composition, fasting-insulin, fasting-glucose, fasting-lipids and cardio-vascular
      fitness were measured. RESULTS: Participants with and without ID differed
      significantly in the prevalence of cardio-metabolic risk factors with
      participants with ID having a higher percentage of total fat mass, wider waist
      circumferences (WCs), lower levels of fat-free mass (FFM), lower bone mineral
      density (BMD) and higher insulin and homeostasis model assessment of insulin
      resistance (HOMA) levels and poorer cardio-vascular fitness. The healthiest
      levels were found in the non-ID-t group compared to the group with ID and the
      group with non-ID-p in between. CONCLUSION: The prevalence of cardio-metabolic
      risk factors and poor cardio-vascular fitness was found to be high in this young
      population with intellectual disabilities. Measures should be taken to improve
      the health messages directed towards children and adolescents with intellectual
      disabilities.

PMID- 19183119
TI  - The diagnostic protocol in children and adolescents with syncope: a multi-centre
      prospective study.
AB  - AIM: The appropriate diagnostic protocol for children with syncope has not been
      well established. A diagnostic protocol was developed and prospectively
      implemented to improve the diagnostic performance of paediatricians. METHODS: The
      study population included 474 consecutive patients (range 6-17 years) presenting
      with a syncopal spell in one of the five participating hospitals of China. In
      step 1, all patients underwent initial evaluation for history, physical
      examination, standing test and standard electrocardiography (ECG). In step 2,
      priority was given to cardiographic tests for possibly cardiogenic syncope, or
      electroencephalographic examination and brain imaging for suspected neurological
      syncope, or psychiatric tests for suspected psychiatric syncope. Patients with
      unexplained syncope underwent head-up tilt testing (HUT). RESULTS: The initial
      evaluation gave a definite diagnosis in 59 (12.4%) and possible diagnosis in 54
      of the 474 patients. Further testing gave a definite diagnosis for 326 patients
      (69.7%). After the entire diagnostic protocol, definite diagnosis was established
      in 385 patients (81.1%). Autonomic-mediated reflex syncope (AMS) accounted for
      73.0% of cases. The average cost of diagnostic results per patient was RMB
      1030.24 +/- 150.09 ($118.42 +/- 17.25). CONCLUSION: The use of a simplified
      diagnostic protocol for children and adolescents with syncope improves diagnostic
      yield.

PMID- 19183120
TI  - Comparison of cytokine responses in nasopharyngeal aspirates from children with
      viral lower respiratory tract infections.
AB  - AIM: To determine whether nasopharyngeal aspirates (NPAs) cytokine response is
      different according to the causative viruses in children with lower respiratory
      tract infections (LRTI). METHODS: NPAs from 277 children with LRTI caused by
      respiratory virus were evaluated. Based on the proven viral agents, LRTI patients
      were divided into four groups. Levels of IL-4, IL-5 and IFN-gamma were determined
      by ELISA. RESULTS: Patients with influenza virus infection demonstrated
      significantly lower IL-4 and IL-5 levels than those with other three groups.
      Patients with respiratory syncytial virus (RSV) infection showed an increase in
      production of IL-4 and IL-5, and a decrease in the IFN-gamma level when compared
      to patients with influenza virus infection. Interestingly, a similar Th2 response
      was seen in patients with parainfluenza virus or adenovirus infection.
      CONCLUSION: These results demonstrate that respiratory viruses can induce
      different local cytokine responses. However, Th2 biased responses are not unique
      for RSV but seem to be predominant in respiratory viruses of young children.

PMID- 19183121
TI  - Variability in pain response to a non-pharmacological intervention across
      repeated routine pain exposure in preterm infants: a feasibility study.
AB  - AIM: To explore the variability in pain response in preterm infants across time
      who received sucrose during routine heel stick. METHOD: Single group, exploratory
      repeated measures design. SETTING: Two tertiary level neonatal intensive care
      units (NICU) in Switzerland. SUBJECTS: Nine preterm infants born between 28 2/7
      and 31 4/7 weeks of gestation during their first 14 days of life. MEASUREMENTS:
      Pain was assessed by the Bernese Pain Scale for Neonates (BPSN), the Premature
      Infant Pain Profile (PIPP) and the Visual Analogue Scale (VAS). Salivary cortisol
      was analysed. RESULTS: 72-94% of the variability was within-subject variability,
      indicating inconsistency of pain responses across the 5 heel sticks. Interrater
      agreement was highest during heel sticks 1-3 and decreased during heel stick 4
      and 5, indicating a possible alteration of pain patterns. No significant
      differences in the amount of cortisol could be detected before and after the heel
      sticks (p = 0.55), indicating no stress-induced peak after the painful
      intervention. However, a general gradual decrease of cortisol levels across time
      could be detected. CONCLUSION: A high variability in pain response among preterm
      neonates across time could be described. Consistency of cortisol levels before
      and after the heel sticks could indicate the effectiveness of sucrose across
      time.

PMID- 19183122
TI  - Interleukin-10 and transforming growth factor-beta1 in cord blood: relationship
      with paternal allergy and cesarean section.
AB  - AIM: To measure Interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF
      beta1) in cord blood and assess their relationship with parental allergy and
      perinatal characteristics. METHODS: In a neonatal care unit 212 consecutive full
      term and appropriate for gestational age newborns were recruited. IL-10 and TGF
      beta1 levels were determined in cord blood by high sensitivity ELISA. Perinatal
      characteristics, mode of delivery and presence of allergy in parents were
      recorded. RESULTS: Out of 212 newborns, 136 were of non-allergic parents and 76
      (35.8%) of one or both allergic parents. In newborns of allergic fathers median
      IL-10 levels tended to be lower (0.67 vs. 1.06 pg/mL, p = 0.07) and TGF-beta1
      levels were significantly lower (40.9 vs. 45.3 ng/mL, p = 0.008) than in newborns
      of non-allergic parents. Multiple general regression analysis showed that
      presence of paternal allergy (beta=-0.19, p = 0.003) to be born by cesarean
      section (beta=-0.21, p = 0.03) and younger gestational age (beta= 0.14, p = 0.04)
      independently contributed to decrease TGF-beta1 levels (multiple R = 0.38, p <
      0.0001). CONCLUSION: Paternal allergy and cesarean section are associated to
      decreased TGF-beta1, which might be the mediator of the increased risk of atopy
      development. Cord blood IL-10 and TGF-beta1 levels of our newborn series could be
      used as reference values for further studies on these relationships.

PMID- 19183123
TI  - Antiphospholipid antibodies and lipoprotein(a) in obese children.
AB  - AIM: Antiphospholipid (aPL) antibodies, Lipoprotein(a) [Lp(a)] and obesity are
      considered three independent risk factors for development of cardiovascular
      diseases. We investigate the presence of aPL antibodies and the Lp(a)
      concentration in 190 obese and 30 healthy children divided into prepubertal and
      pubertal, compared with healthy adults. RESULTS: aPL antibodies were detected in
      2.65% of prepubertal and in 2.59% of pubertal obese children. Considering results
      obtained by Lp(a) test, 4.4% of prepubertal and 5.2% of pubertal obese children
      and 17.5% of healthy adults were at risk for development of cardiovascular
      diseases. CONCLUSION: The presence of various prothrombotic risk factors
      increases the probability of developing thrombosis. Considering aPL antibodies
      there is no statistically significant difference among the different considered
      groups; therefore each category has the same risk factor. The Lp(a) distribution
      in adults is significantly different from the Lp(a) distribution in prepubertal
      (p = 0.012) and pubertal (p = 0.029) obese children. There is no significant
      difference among prepubertal subjects (p = 0.632) as well as pubertal subjects (p
      = 0.465), independently from the BMI. These results suggest the control of BMI in
      young population to avoid the presence of the obesity as another independent
      prothrombotic risk factor to be added to aPL and Lp(a) in the future adulthood.

PMID- 19183124
TI  - Acute non-oliguric kidney failure and cholestatic hepatitis induced by ibuprofen
      and acetaminophen: a case report.
AB  - The combined use of acetaminophen with ibuprofen has long been in clinical use
      because the target of action of each drug is different and they do not interfere
      with each other. Appropriate dosing and managing of these drugs do not likely
      lead to organ toxicity. However, both acetaminophen and ibuprofen can induce
      liver problems and acute kidney failure, respectively, if administered at high
      doses. We report the case of a female child, in treatment with both acetaminophen
      and ibuprofen, administered at therapeutic antipyretic doses in condition of
      volume depletion, who suffered acute kidney and liver failure. CONCLUSION: The
      combined ibuprofen and acetaminophen treatment, even if administered at
      therapeutic dosages and in a reduced number of doses, may be dangerous in
      conditions of volume depletion.

PMID- 19183125
TI  - Atypical depression is associated with suicide attempt in bipolar disorder.
AB  - OBJECTIVE: There is a dearth of research focusing on factors associated with
      suicide attempts. High rates of atypical depression have been reported in studies
      including unipolar and bipolar II patients. In this study, the association
      between suicide attempt and atypical depression, in addition to other major risk
      factors, was evaluated in 390 bipolar I and II out-patients. METHOD: Variables
      were defined according to DSM-IV criteria, and assessed with a Structured
      Interview for DSM-IV (axis I and II). History of suicide attempt was obtained
      through interviews with patients and relatives. Attempters and non-attempters
      were compared using univariate and multivariate analysis. RESULTS: Attempters
      showed significantly higher rates of atypical depression, family history of
      completed suicide, depression at index episode and cluster B personality
      disorder. CONCLUSION: Our results highlight the relevance of atypical depression
      in bipolar disorder. A more accurate identification of potential attempters may
      contribute to the development of effective preventive treatment strategies.

PMID- 19183126
TI  - Predictors of response to Systems Training for Emotional Predictability and
      Problem Solving (STEPPS) for borderline personality disorder: an exploratory
      study.
AB  - OBJECTIVE: Few predictors of treatment outcome or early discontinuation have been
      identified in persons with borderline personality disorder (BPD). AIM: The aim of
      the study was to examine the relationship between baseline clinical variables and
      treatment response and early discontinuation in a randomized controlled trial of
      System Training for Emotional Predictability and Problem Solving, a new cognitive
      group treatment. METHOD: Improvement was rated using the Zanarini Rating Scale
      for BPD, the Clinical Global Impression Scale, the Global Assessment Scale and
      the Beck Depression Inventory. Subjects were assessed during the 20 week trial
      and a 1-year follow-up. RESULTS: Higher baseline severity was associated with
      greater improvement in global functioning and BPD-related symptoms. Higher
      impulsivity was predictive of early discontinuation. Optimal improvement was
      associated with attending > or = 15 sessions. CONCLUSION: Subjects likely to
      improve have the more severe BPD symptoms at baseline, while high levels of
      impulsivity are associated with early discontinuation.

PMID- 19183127
TI  - A double-blind, placebo-controlled trial of rosiglitazone for clozapine-induced
      glucose metabolism impairment in patients with schizophrenia.
AB  - OBJECTIVE: The primary purpose of this 8-week double-blind, placebo-controlled
      trial of rosiglitazone 4 mg/day was to examine its effect on insulin sensitivity
      index (SI) and glucose utilization (SG) in clozapine-treated subjects with
      schizophrenia with insulin resistance. METHOD: Eighteen subjects were randomized
      and accessed with a Frequently Sampled Intravenous Glucose Tolerance Test
      (FSIVGTT) at baseline and at week 8 to estimate SG and SI. RESULTS: Controlling
      for the baseline, comparing the rosiglitazone group with placebo group, there was
      a non-significant improvement in SG (0.016 +/- 0.006-0.018 +/- 0.008, effect size
      = 0.23, P = 0.05) with a trend of improvement in SI in the rosiglitazone group
      (4.6 +/- 2.8-7.8 +/- 6.7, effect size = 0.18, P = 0.08). There was a significant
      reduction in small low-density lipoprotein cholesterol (LDL-C) particle number
      (987 +/- 443-694 +/- 415, effect size = 0.30, P = 0.04). CONCLUSION:
      Rosiglitazone may have a role in addressing insulin resistance and lipid
      abnormalities associated with clozapine.

PMID- 19183128
TI  - Repeated high-frequency transcranial magnetic stimulation over the dorsolateral
      prefrontal cortex reduces cigarette craving and consumption.
AB  - AIMS: To evaluate the effect of repeated high-frequency transcranial magnetic
      stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC), combined
      with either smoking or neutral cues, on cigarette consumption, dependence and
      craving. DESIGN: Participants were divided randomly to real and sham stimulation
      groups. Each group was subdivided randomly into two subgroups presented with
      either smoking-related or neutral pictures just before the daily TMS
      intervention. Ten daily rTMS sessions were applied every week-day and then a
      maintenance phase was conducted in which rTMS sessions were less frequent.
      SETTING: Single-site, out-patient, randomized, double-blind, sham-controlled.
      PARTICIPANTS: Forty-eight chronic smokers who smoked at least 20 cigarettes per
      day and were motivated to quit smoking. Healthy males and females were recruited
      from the general population using advertisements in newspapers and on internet
      websites. INTERVENTION: Ten daily rTMS sessions were administered using a
      standard figure-8 coil over the DLPFC. Stimulation included 20 trains/day at 100%
      of motor threshold. Each train consisted of 50 pulses at 10 Hz with an inter
      train interval of 15 seconds. MEASUREMENTS: Cigarette consumption was evaluated
      objectively by measuring cotinine levels in urine samples and subjectively by
      participants' self-reports. Dependence and craving were evaluated by standard
      questionnaires. FINDINGS: Ten daily rTMS sessions over the DLPFC reduced
      cigarette consumption and nicotine dependence. Furthermore, treatment blocked the
      craving induced by daily presentation of smoking-related pictures. However, these
      effects tended to dissipate over time. CONCLUSIONS: Multiple high-frequency rTMS
      of the DLPFC can attenuate nicotine craving.

PMID- 19183129
TI  - Can we identify genes for alcohol consumption in samples ascertained for
      heterogeneous purposes?
AB  - BACKGROUND: Previous studies have identified evidence of genetic influence on
      alcohol use in samples selected to be informative for alcoholism research.
      However, there are a growing number of genome-wide association studies (GWAS)
      using samples unselected for alcohol consumption (i.e., selected on other traits
      and forms of psychopathology), which nevertheless assess consumption as a risk
      factor. Is it reasonable to expect that genes contributing to variation in
      alcohol consumption can be identified in such samples? METHODS: An exploratory
      approach was taken to determine whether linkage analyses for heaviness of alcohol
      consumption, using a sample collected for heterogeneous purposes, could replicate
      previous findings. Quantity and frequency measures of consumption were collected
      in telephone interviews from community samples. These measures, and genotyping,
      were available for 5,441 individuals (5,067 quasi-independent sibling pairs). For
      1,533 of these individuals, data were collected on 2 occasions, about 8.2 years
      apart, providing 2 datasets that maximize data collected at either a younger or
      an older age. Analyses were conducted to address the question of whether age and
      heavier levels of alcohol consumption effects outcome. Linkage results were
      compared in the younger and older full samples, and with samples in which
      approximately 10, 20, and 40 of drinkers from the lower end of the distribution
      of alcohol consumption were dropped. RESULTS: Linkage peaks varied for the age
      differentiated samples and for percentage of light drinkers retained. Larger
      peaks (LOD scores >2.0) were typically found in regions previously identified in
      linkage studies and/or containing proposed candidate genes for alcoholism
      including AGT, CARTPT, OPRD1, PIK3R1, and PDYN. CONCLUSIONS: The results suggest
      that GWAS assessing alcohol consumption as a covariate for other conditions will
      have some success in identifying genes contributing to consumption-related
      variation. However, sample characteristics, such as participant age, and trait
      distribution, may have substantial effects on the strength of the genetic signal.
      These results can inform forthcoming GWAS where the same restrictions apply.

PMID- 19183130
TI  - Patterns of ethanol intake in preadolescent, adolescent, and adult Wistar rats
      under acquisition, maintenance, and relapse-like conditions.
AB  - BACKGROUND: Animal behavioral models of voluntary ethanol consumption represent a
      valuable tool to investigate the relationship between age and propensity to
      consume alcohol using an experimental methodology. Although adolescence has been
      considered as a critical age, few are the studies that consider the
      preadolescence age. This study examines the ethanol consumption/preference and
      the propensity to show an alcohol deprivation effect (ADE) after a short
      voluntary ethanol exposure from a developmental perspective. METHODS: Three
      groups of heterogeneous Wistar rats of both sexes with ad libitum food and water
      were exposed for 10 days to 3 ethanol solutions at 3 different ontogenetic
      periods: preadolescence (PN19), adolescence (PN28), and adulthood (PN90). Ethanol
      intake (including circadian rhythm), ethanol preference, water and food
      consumption, and ADE were measured. RESULTS: During the exposure, the 3 groups
      differed in their ethanol intake; the greatest amount of alcohol (g/kg) was
      consumed by the preadolescent rats while the adolescents showed a progressive
      decrease in alcohol consumption as they approached the lowest adult levels by the
      end of the assessed period. The pattern of ethanol consumption was not fully
      explained in terms of hyperphagia and/or hyperdipsia at early ages, and showed a
      wholly circadian rhythm in adolescent rats. After an abstinence period of 7 days,
      adult rats showed an ADE measured both as an increment in ethanol consumption and
      preference, whereas adolescent rats only showed an increment in ethanol
      preference. Preadolescent rats decreased their consumption and their preference
      remained unchanged. CONCLUSIONS: In summary, using a short period of ethanol
      exposure and a brief deprivation period the results revealed a direct
      relationship between chronological age and propensity to consume alcohol, being
      the adolescence a transition period from the infant to the adult pattern of
      alcohol consumption. Preadolescent animals showed the highest ethanol consumption
      level. The ADE was only found in adult animals for both alcohol consumption and
      preference, whereas adolescents showed an ADE only for preference. No effect of
      sex was detected in any phase of the experiment.

PMID- 19183131
TI  - Disparities in alcohol-related problems among white, black, and Hispanic
      Americans.
AB  - BACKGROUND: This study assesses racial/ethnic disparities in negative social
      consequences of drinking and alcohol dependence symptoms among white, black, and
      Hispanic Americans. We examine whether and how disparities relate to heavy
      alcohol consumption and pattern, and the extent to which social disadvantage
      (poverty, unfair treatment, and racial/ethnic stigma) accounts for observed
      disparities. METHODS: We analyzed data from the 2005 U.S. National Alcohol
      Survey, a nationally representative telephone-based survey of adults ages 18 and
      older (N = 6,919). Given large racial/ethnic differences in abstinence rates,
      core analyses were restricted to current drinkers (N = 4,080). Logistic
      regression was used to assess disparities in alcohol-related problems at 3 levels
      of heavy drinking, measured using a composite variable incorporating frequency of
      heavy episodic drinking, frequency of drunkenness, and maximum amount consumed in
      a single day. A mediational approach was used to assess the role of social
      disadvantage. RESULTS: African American and Hispanic drinkers were significantly
      more likely than white drinkers to report social consequences of drinking and
      alcohol dependence symptoms. Even after adjusting for differences in heavy
      drinking and demographic characteristics, disparities in problems remained. The
      racial/ethnic gap in alcohol problems was greatest among those reporting little
      or no heavy drinking, and gradually diminished to nonsignificance at the highest
      level of heavy drinking. Social disadvantage, particularly in the form of
      racial/ethnic stigma, appeared to contribute to racial/ethnic differences in
      problems. CONCLUSIONS: These findings suggest that to eliminate racial/ethnic
      disparities in alcohol-related problems, public health efforts must do more than
      reduce heavy drinking. Future research should address the possibility of drink
      size underestimation, identify the particular types of problems that
      disproportionately affect racial/ethnic minorities, and investigate social and
      cultural determinants of such problems.

PMID- 19183132
TI  - Response inhibition moderates the relationship between implicit associations and
      drinking behavior.
AB  - BACKGROUND: Contemporary dual-process models of alcohol abuse propose that
      alcohol abuse develops because of dysfunctions in the impulsive system, which
      generates automatic impulses to drink alcohol, and disruptions in the reflective
      system, which becomes unable to inhibit the influence of these automatic
      impulses. Based on these insights, this study investigated whether individual
      differences in the ability of the reflective system to exert response inhibition
      moderate the relationship between automatic cognitive processes and drinking
      behavior. Specifically, it was examined whether the interaction between implicit
      alcohol-related associations and response inhibition predicted drinking behavior.
      METHODS: Seventy-one university students completed the study online via the
      Internet. Implicit alcohol associations with positive affect and with arousal
      were assessed with variants of the Implicit Association Test. Response inhibition
      was measured using the original Stroop task. Participants also reported their
      weekly alcohol use and alcohol-related problems. RESULTS: As predicted, implicit
      associations were unrelated to drinking behavior when response inhibition was
      high. In contrast, when response inhibition was low, stronger implicit
      associations between alcohol and positive affect predicted increased alcohol use
      and alcohol-related problems. CONCLUSIONS: These findings indicate that the
      relationship between automatic cognitive processes, originating in the impulsive
      system, and drinking behavior depends on individual differences in response
      inhibition exerted by the reflective system. As prolonged alcohol abuse is known
      to impair response inhibition, alcohol abusers may benefit from interventions
      that increase response inhibition, thereby restoring inhibitory control over
      automatic impulses.

PMID- 19183133
TI  - Effects of alcohol on performance on a distraction task during simulated driving.
AB  - BACKGROUND: Prior studies report that accidents involving intoxicated drivers are
      more likely to occur during performance of secondary tasks. We studied this
      phenomenon, using a dual-task paradigm, involving performance of a visual oddball
      (VO) task while driving in an alcohol challenge paradigm. Previous functional MRI
      (fMRI) studies of the VO task have shown activation in the anterior cingulate,
      hippocampus, and prefrontal cortex. Thus, we predicted dose-dependent decreases
      in activation of these areas during VO performance. METHODS: Forty healthy social
      drinkers were administered 3 different doses of alcohol, individually tailored to
      their gender and weight. Participants performed a VO task while operating a
      virtual reality driving simulator in a 3T fMRI scanner. RESULTS: Analysis showed
      a dose-dependent linear decrease in Blood Oxygen Level Dependent activation
      during task performance, primarily in hippocampus, anterior cingulate, and
      dorsolateral prefrontal areas, with the least activation occurring during the
      high dose. Behavioral analysis showed a dose-dependent linear increase in
      reaction time, with no effects associated with either correct hits or false
      alarms. In all dose conditions, driving speed decreased significantly after a VO
      stimulus. However, at the high dose this decrease was significantly less.
      Passenger-side line crossings significantly increased at the high dose.
      CONCLUSIONS: These results suggest that driving impairment during secondary task
      performance may be associated with alcohol-related effects on the above brain
      regions, which are involved with attentional processing/decision-making. Drivers
      with high blood alcohol concentrations may be less able to orient or detect novel
      or sudden stimuli during driving.

PMID- 19183134
TI  - Contribution of NADH increases to ethanol's inhibition of retinol oxidation by
      human ADH isoforms.
AB  - BACKGROUND: A decrease in retinoic acid levels due to alcohol consumption has
      been proposed as a contributor to such conditions as fetal alcohol spectrum
      diseases and ethanol-induced cancers. One molecular mechanism, competitive
      inhibition by ethanol of the catalytic activity of human alcohol dehydrogenase
      (EC 1.1.1.1) (ADH) on all-trans-retinol oxidation has been shown for the ADH7
      isoform. Ethanol metabolism also causes an increase in the free reduced
      nicotinamide adenine dinucleotide (NADH) in cells, which might reasonably be
      expected to decrease the retinol oxidation rate by product inhibition of ADH
      isoforms. METHODS: To understand the relative importance of these two mechanisms
      by which ethanol decreases the retinol oxidation in vivo we need to assess them
      quantitatively. We have built a model system of 4 reactions: (1) ADH oxidation of
      ethanol and NAD(+), (2) ADH oxidation of retinol and NAD(+), (3) oxidation of
      ethanol by a generalized Ethanol(oxidase) that uses NAD(+), (4) NADH(oxidase)
      which carries out NADH turnover. RESULTS: Using the metabolic modeling package
      ScrumPy, we have shown that the ethanol-induced increase in NADH contributes from
      0% to 90% of the inhibition by ethanol, depending on (ethanol) and ADH isoform.
      Furthermore, while the majority of flux control of retinaldehyde production is
      exerted by ADH, Ethanol(oxidase) and the NADH(oxidase) contribute as well.
      CONCLUSIONS: Our results show that the ethanol-induced increase in NADH makes a
      contribution of comparable importance to the ethanol competitive inhibition
      throughout the range of conditions likely to occur in vivo, and must be
      considered in the assessment of the in vivo mechanism of ethanol interference
      with fetal development and other diseases.

PMID- 19183136
TI  - Adverse drinking-related consequences among lower income, racial, and ethnic
      minority drinkers: cross-sectional results.
AB  - OBJECTIVE: To examine factors associated with adverse consequences of alcohol
      consumption among a community sample of drinkers in a low-income, racial, and
      ethnic minority community. METHODS: A sample of 329 drinkers was recruited from
      17 randomly selected off-sell alcohol outlets in South Los Angeles. Respondents
      were interviewed by trained research personnel on their demographic
      characteristics, income, drinking patterns and preferences, and alcohol-related
      adverse consequences (using the Drinkers Inventory of Consequences--DrInC), among
      other items. We developed logistic regression models predicting high scores on
      DrInC total score and subscales (impulse control, interpersonal, intrapersonal,
      physical, and social responsibility). RESULTS: In this sample, we found drinking
      patterns--bingeing, drinking outdoors, drinking in the morning--to be
      significantly associated with total DrInC scores and some subscales. Malt liquor
      beverage (MLB) use was significantly associated with total DrInC score and
      interpersonal and social responsibility subscales. Previous alcohol treatment
      predicted all but 1 DrInC subscale and total score. CONCLUSIONS: A diverse array
      of factors predicted high DrInC total and subscale scores. More research on the
      association between MLB use and consequences is required. In addition, studies
      with community samples are likely to further enrich our understanding of the
      interactions between drinking patterns and preferences, settings, and negative
      consequences.

PMID- 19183137
TI  - A metric of maternal prenatal risk drinking predicts neurobehavioral outcomes in
      preschool children.
AB  - BACKGROUND: Fetal Alcohol Spectrum Disorders (FASDs), including Fetal Alcohol
      Syndrome, continue to be high-incidence developmental disorders. Detection of
      patterns of maternal drinking that place fetuses at risk for these disorders is
      critical to diagnosis, treatment, and prevention, but is challenging and often
      insufficient during pregnancy. Various screens and measures have been used to
      identify maternal risk drinking but their ability to predict child outcome has
      been inconsistent. This study hypothesized that a metric of fetal "at-risk"
      alcohol exposure (ARAE) derived from several indicators of maternal self-reported
      drinking would predict alcohol-related neurobehavioral dysfunctions in children
      better than individual measures of maternal alcohol consumption alone. METHODS:
      Self-reported peri-conceptional and repeated maternal drinking during pregnancy
      were assessed with semi-structured interviews and standard screens, i.e., the
      CAGE, T-ACE, and MAST, in a prospective sample of 75 African-American mothers.
      Drinking volumes per beverage type were converted to standard quantity and
      frequency measures. From these individual measures and screening instruments, a
      simple dichotomous index of prenatal ARAE was defined and used to predict
      neurobehavioral outcomes in the 4- to 5-year-old offspring of these women. Study
      outcomes included IQ, attention, memory, visual-motor integration, fine motor
      skill, and behavior. Statistical analyses controlled for demographic and other
      potential confounders. RESULTS: The current "at-risk" drinking metric identified
      over 62% of the mothers as drinking at risk levels--23% more than the selection
      criterion identified--and outperformed all individual quantity and frequency
      consumption measures, including averages of weekly alcohol use and "binge"
      alcohol exposures (assessed as intake per drinking occasion), as well as an
      estimate of the Maternal Substance Abuse Checklist (Coles et al., 2000), in
      predicting prenatal alcohol-related cognitive and behavioral dysfunction in 4- to
      5-year-old children. CONCLUSIONS: A metric reflecting multiple indices of "at
      risk" maternal alcohol drinking in pregnancy had greater utility in predicting
      various prenatal alcohol-related neurobehavioral dysfunction and deficits in
      children compared to individual measures of maternal self-reported alcohol
      consumption or a previous maternal substance abuse index. Assessing fetal risk
      drinking in pregnant women was improved by including multiple indicators of both
      alcohol consumption and alcohol-related consequences and, if appropriate
      practical applications are devised, may facilitate intervention by health care
      workers during pregnancy and potentially reduce the incidence or severity of
      FASDs.

PMID- 19183135
TI  - A Rasch model analysis of alcohol consumption and problems across adolescence and
      young adulthood.
AB  - BACKGROUND: Recent investigations using item response modeling have begun to
      conceptualize alcohol consumption, problems, and dependence as representing
      points along a single continuum of alcohol involvement. Such a conceptualization
      may be of particular benefit to measurement of alcohol involvement in
      adolescents, but investigations to date have been limited to adult samples and
      may not generalize to adolescents due to age-related developmental differences.
      METHODS: This study used Rasch model analyses to examine the properties of
      indices of alcohol consumption and problems among 6,353 adolescents, aged 12 to
      18 years, in Wave 1 of the Add Health survey. A particular focus was on whether
      the functioning of items changed when these adolescents were re-interviewed in
      Wave 3 when they were 18 to 24 years of age. RESULTS: Rasch model analyses
      supported the unidimensionality and additive properties of the items in the Wave
      1 data. Comparisons of Wave 1 and Wave 3 data indicated differential item
      functioning in most of the items such that items related to alcohol consumption
      were more severe during adolescence, whereas items related to alcohol problems
      were more severe in young adulthood. CONCLUSIONS: A valid index of alcohol
      involvement in adolescents can be constructed combining indices of alcohol
      consumption and alcohol problems. Such an index covers a range of severity and
      functions similarly across sex and race/ethnicity. A similar index can be
      constructed in young adulthood. However, the interpretation of scores must be
      attentive to developmental differences. In particular, for adolescents, indices
      of alcohol consumption are relatively closer in severity to indices of alcohol
      problems than they are among young adults. Thus, alcohol problems are more likely
      among adolescents than young adults given a similar level of drinking.

PMID- 19183138
TI  - Alcohol stimulates ciliary motility of isolated airway axonemes through a nitric
      oxide, cyclase, and cyclic nucleotide-dependent kinase mechanism.
AB  - BACKGROUND: Lung mucociliary clearance provides the first line of defense from
      lung infections and is impaired in individuals who consume heavy amounts of
      alcohol. Previous studies have demonstrated that this alcohol-induced ciliary
      dysfunction occurs through impairment of nitric oxide (NO) and cyclic nucleotide
      dependent kinase-signaling pathways in lung airway ciliated epithelial cells.
      Recent studies have established that all key elements of this alcohol-driven
      signaling pathway co-localize to the apical surface of the ciliated cells with
      the basal bodies. These findings led us to hypothesize that alcohol activates the
      cilia stimulation pathway at the organelle level. To test this hypothesis we
      performed experiments exposing isolated demembranated cilia (isolated axonemes)
      to alcohol and studied the effect of alcohol-stimulated ciliary motility on the
      pathways involved with isolated axoneme activation. METHODS: Isolated
      demembranated cilia were prepared from bovine trachea and activated with
      adenosine triphosphate. Ciliary beat frequency, NO production, adenylyl and
      guanylyl cyclase activities, cAMP- and cGMP-dependent kinase activities were
      measured following exposure to biologically relevant concentrations of alcohol.
      RESULTS: Alcohol rapidly stimulated axoneme beating 40% above baseline at very
      low concentrations of alcohol (1 to 10 mM). This activation was specific to
      ethanol, required the synthesis of NO, the activation of soluble adenylyl cyclase
      (sAC), and the activation of both cAMP- and cGMP-dependent kinases (PKA and PKG),
      all of which were present in the isolated organelle preparation. CONCLUSIONS:
      Alcohol rapidly and sequentially activates the eNOS-->NO-->GC-->cGMP-->PKG and
      sAC-->cAMP--> PKA dual signaling pathways in isolated airway axonemes. These
      findings indicate a direct effect of alcohol on airway cilia organelle function
      and fully recapitulate the alcohol-driven activation of cilia known to exist in
      vivo and in intact lung ciliated cells in vitro following brief moderate alcohol
      exposure. Furthermore, these findings indicate that airway cilia are exquisitely
      sensitive to the effects of alcohol and substantiate a key role for alcohol in
      the alterations of mucociliary clearance associated with even low levels of
      alcohol intake. We speculate that this same axoneme-based alcohol activation
      pathway is down regulated following long-term high alcohol exposure and that the
      isolated axoneme preparation provides an excellent model for studying the
      mechanism of alcohol-mediated cilia dysfunction.

PMID- 19183140
TI  - Dietary zinc supplementation throughout pregnancy protects against fetal
      dysmorphology and improves postnatal survival after prenatal ethanol exposure in
      mice.
AB  - BACKGROUND: We have previously demonstrated that ethanol teratogenicity is
      associated with metallothionein-induced fetal zinc (Zn) deficiency, and that
      maternal subcutaneous Zn treatment given with ethanol in early pregnancy prevents
      fetal abnormalities and spatial memory impairments in mice. Here we investigated
      whether dietary Zn supplementation throughout pregnancy can also prevent ethanol
      related dysmorphology. METHODS: Pregnant mice were injected with saline or 25%
      ethanol (0.015 ml/g intraperitoneally at 0 and 4 hours) on gestational day (GD) 8
      and fed either a control (35 mg Zn/kg) or a Zn-supplemented diet (200 mg Zn/kg)
      from GD 0 to 18. Fetuses from the saline, saline + Zn, ethanol and ethanol + Zn
      groups were assessed for external birth abnormalities on GD 18. In a separate
      cohort of mice, postnatal growth and survival of offspring from these treatment
      groups were examined from birth until postnatal day 60. RESULTS: Fetuses from
      dams treated with ethanol alone in early pregnancy had a significantly greater
      incidence of physical abnormalities (26%) compared to those from the saline
      (10%), saline + Zn (9%), or ethanol + Zn (12%) groups. The incidence of
      abnormalities in ethanol + Zn-supplemented fetuses was not different from saline
      treated fetuses. While ethanol exposure did not affect the number of fetal
      resorptions or pre- or postnatal weight, there were more stillbirths with ethanol
      alone, and cumulative postnatal mortality was significantly higher in offspring
      exposed to ethanol alone (35% deaths) compared to all other treatment groups
      (13.5 to 20.5% deaths). Mice supplemented with Zn throughout pregnancy had higher
      plasma Zn concentrations than those in un-supplemented groups. CONCLUSIONS: These
      findings demonstrate that dietary Zn supplementation throughout pregnancy
      ameliorates dysmorphology and postnatal mortality caused by ethanol exposure in
      early pregnancy.

PMID- 19183139
TI  - Long-term behavioral changes in response to early developmental exposure to
      ethanol in zebrafish.
AB  - BACKGROUND: Zebrafish is becoming an important research tool for the analysis of
      brain function and behavior. It has been proposed to model human alcoholism as
      well as fetal alcohol syndrome. Previous studies investigating the consequences
      of exposure to ethanol during early development of zebrafish employed robust
      dosing regimens (high ethanol concentration and long exposure) that may model a
      rare situation in the human clinic. These studies found major structural
      abnormalities developing in the exposed fish. METHODS: Here we hope to avoid such
      gross changes and administer only low doses of ethanol (0.00, 0.25, 0.50, 0.75,
      1.00 vol/vol %) at 24-hour postfertilization and for only a short period of time
      (for 2 hours). We analyze the behavior of exposed fish at adult stage using
      computerized stimulus presentation and automated videotracking response
      quantification. RESULTS: Despite the short ethanol exposure period and the modest
      concentrations, significant behavioral alterations were found: fish exposed to
      higher doses of ethanol swam at an increased distance from a computer-animated
      zebrafish shoal while their activity levels did not change. CONCLUSIONS: Although
      the interpretation of and the mechanisms underlying this finding will require
      further investigation, the results suggest that zebrafish will be an appropriate
      model organism for the analysis of the effects of moderate to mild prenatal
      ethanol exposure.

PMID- 19183141
TI  - Effects of acute alcohol intoxication and paroxetine on aggression in men.
AB  - BACKGROUND: The purpose of this study was to examine the role of the serotonin (5
      HT) system in alcohol-related aggression. METHODS: Specifically, we
      experimentally examined the effects of 5-HT augmentation on alcohol-related
      aggression in men (n = 56). After consuming either alcohol (mean blood alcohol
      concentration of 0.10%) or a placebo (no alcohol) drink, and taking either 20 mg
      of paroxetine (Paxil) or a placebo pill, participants were provided the
      opportunity to administer electric shock to a (faux) opponent during a task
      disguised as a reaction-time game. Aggression was defined as the intensity of
      shock chosen and the frequency with which an extreme (clearly painful) shock was
      chosen. We predicted that 5-HT augmentation would be associated with lower
      aggressive behavior overall, and also reduce the aggression facilitating effects
      of acute alcohol intoxication. RESULTS: The results indicated that alcohol
      intoxication increased aggression, particularly under low provocation. Paroxetine
      decreased aggression, particularly during high provocation. These effects,
      however, occurred independently of each other. CONCLUSIONS: The effect of alcohol
      on extreme aggression was moderated by previous aggression history, with more
      aggressive individuals showing greater alcohol-related increases in extreme
      aggression.

PMID- 19183142
TI  - Mercaptopurine treatment should be considered in azathioprine intolerant patients
      with inflammatory bowel disease.
AB  - BACKGROUND: Adverse drug reactions are a significant reason for therapeutic
      failure during thiopurine treatment of inflammatory bowel disease. Some smaller
      series in this patient population have shown that a switch to mercaptopurine may
      be successful in many cases of azathioprine intolerance. AIM: To assess the long
      term outcome of mercaptopurine treatment in a large patient population with
      azathioprine intolerance. METHODS: We identified 135 patients (74 women; median
      age 40 years) with Crohn's disease (n = 88) or ulcerative colitis (n = 47) and
      reviewed their medical records. RESULTS: A total of 70 patients (52%) tolerated
      mercaptopurine and were followed up for 736 (362-1080) days; 65 patients
      discontinued mercaptopurine due to adverse events after 25 (8-92) days.
      Mercaptopurine was tolerated in 71% (12/17) with hepatotoxicity and in 68%
      (13/19) with arthralgia/myalgia during azathioprine treatment. Previous abdominal
      surgery was more common in mercaptopurine intolerant patients [39/65 (60%) vs.
      27/70 (39%); P = 0.02] and thiopurine methyltransferase activity was higher in
      mercaptopurine tolerant patients than in mercaptopurine intolerant patients [13.2
      (11.4-15.3) vs. 11.8 (9.6-14.2) U/mL red blood cells; P = 0.04; n = 81].
      CONCLUSIONS: A trial of mercaptopurine should be considered in azathioprine
      intolerance, as half of the patients tolerate a switch to mercaptopurine.
      Patients with hepatotoxicity or arthralgia/myalgia during azathioprine treatment
      might benefit more often than those with other types of adverse events.

PMID- 19183143
TI  - Proton pump inhibitors increase significantly the risk of Clostridium difficile
      infection in a low-endemicity, non-outbreak hospital setting.
AB  - BACKGROUND: Proton pump inhibitors (PPI) have been linked to higher risk of
      Clostridium difficile infection (CDI). The relevance of this association in
      hospitals with low disease activity, where an outbreak strain is nondominant, has
      been assessed in relatively few studies. AIM: To assess the association of PPI
      and CDI in a setting of low disease activity. METHODS: A retrospective cohort
      study was conducted at two hospitals. Patients admitted for > or = 7 days
      receiving antibiotics were included. Demographics, exposure to PPI, antibiotics
      and other drugs in relation to diagnosis of CDI were assessed by univariate and
      multivariate analyses. RESULTS: Of 14 719 patients, 149 (1%) first episode CDI
      were documented; PPI co-exposure increased CDI [1.44 cases/100 patients vs. 0.74
      cases/100 non-exposed (OR: 1.96, 95% CI: 1.42-2.72)]. By logistic regression, PPI
      days (adjusted OR: 1.01 per day, 95% CI: 1.00-1.02), histamine-2 blockers,
      antidepressants, antibiotic days, exposure to medications, age, admission service
      and length of admission were significant predictors. CONCLUSIONS: A statistically
      significant increase in CDI was observed in antibiotic recipients who received
      PPI, but the absolute risk increase is modest. In settings of with low rates of
      CDI, the benefit of PPI therapy outweighs the risk of developing CDI. These data
      support programmes to decrease inappropriate use of PPI in hospitalized patients.

PMID- 19183144
TI  - Patient acceptance and clinical impact of Bravo monitoring in patients with
      previous failed catheter-based studies.
AB  - BACKGROUND: Standard pH monitoring is performed over 24 h with a naso-oesophageal
      catheter (C-pH). Limitations include naso-pharyngeal discomfort, nausea and
      social embarrassment resulting in reduced reflux-provoking activities. Recently a
      catheter-free pH-monitoring technique has become available. The tolerability and
      diagnostic yield of this system in patients who failed standard monitoring remain
      unknown. AIM: To examine the tolerability and diagnostic outcome of catheter-free
      pH-monitoring technique in patients who failed standard monitoring. METHODS:
      Patients referred for C-pH and catheter-free pH monitoring completed a
      tolerability questionnaire. Acid exposure in the distal oesophagus and symptom
      index (SI) were reviewed. RESULTS: Over 4 years, 883/1751 (50%) of patients with
      typical reflux symptoms referred for C-pH were diagnosed with gastro-oesophageal
      reflux disease (GERD) based on a pathological percentage time acid exposure
      (%time pH <4);134 (8%) patients failed C-pH and, of these, 129 successfully
      completed 2-day catheter-free pH monitoring. Ninety-eight (76%) of these patients
      had a pathological percentage pH <4 on either day compared with 49/102 (49%) of
      contemporaneous C-pH patients (P < 0.01). There was no difference in SI for
      heartburn (35% vs. 42%; P = 0.49). The questionnaire demonstrated a preference
      for catheter-free pH monitoring (96%) with less restriction in activities of
      daily living, naso-pharyngeal discomfort, dysphagia and chest pain. CONCLUSIONS:
      Tolerance and satisfaction with catheter-free pH monitoring are high in patients
      who had previously failed C-pH; catheter-free pH monitoring assists the
      definitive diagnosis of GERD in this group.

PMID- 19183145
TI  - International validation of a health-related quality of life questionnaire in
      patients with erosive gastro-oesophageal reflux disease.
AB  - BACKGROUND: Although erosive gastro-oesophageal reflux disease (GERD) is a highly
      prevalent condition, there is no specific, valid, reliable and sensitive
      questionnaire that allows evaluating treatment-induced changes in health-related
      quality of life (HRQoL). AIM: To design a self-administered questionnaire, the
      GERD Analyzer (GERDyzer), for use in clinical studies. METHODS: The GERDyzer
      comprises 10 dimensions each illustrated by pictogram-like drawings, simplifying
      communication with the patients. Self-assessment is performed by 100 mm Visual
      Analogue Scales. For validation, a 5-week clinical trial involving 395 patients
      (per-protocol) with oesophagitis was conducted. Patients were treated with
      pantoprazole (40 mg o.d.) for 28 days. Psychometric analyses included internal
      consistency, test-retest reliability, responsiveness and construct validity.
      RESULTS: Factor analysis showed consistency of the dimensions and no reduction
      was necessary. Validation of GERDyzer indicated high internal consistency
      (Cronbach's alpha = 0.95) and test-retest reliability (intraclass correlation
      coefficient =0.91). Responsiveness of the total score expressed by nonparametric
      effect size was 1.38. Comparison of scores with other questionnaires resulted in
      logical correlation levels depending on the respected concepts measured.
      Conclusions GERDyzer proved to be highly valid, reproducible and responsive. It
      allows reliably assessing treatment-induced changes in HRQoL in erosive GERD.

PMID- 19183146
TI  - Health-related quality of life in patients with gastro-oesophageal reflux disease
      under routine care: 5-year follow-up results of the ProGERD study.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GERD) is a common disorder
      associated with substantial reductions in health-related quality of life (HRQL).
      AIM: To describe patterns of change in HRQL during 5 years of follow-up in a
      large population of GERD patients. METHODS: In 2000, a total of 6215 GERD
      patients were enrolled in the Progression of GERD (ProGERD) study. During follow
      up, patients received any medication considered necessary. HRQL was assessed
      yearly with the Short-Form 36 and the Quality of Life in Reflux and Dyspepsia
      (QOLRAD) questionnaires. Associations between patient characteristics and changes
      in HRQL were analysed using multiple logistic regression models. RESULTS: After 5
      years, data on HRQL were available for 4597 (74%) patients. Both generic and
      disease-specific HRQL improved after baseline and remained well above baseline
      levels in the following years. A clinically relevant decrease in QOLRAD scores
      was reported by 3-5% of patients. According to our multivariate analysis, a
      decrease in HRQL was associated with a higher reflux symptom load and the
      presence of night-time heartburn. CONCLUSIONS: Only a small minority of the
      ProGERD population reported a clinically relevant decrease in HRQL, which was
      associated most strongly with nocturnal heartburn.

PMID- 19183147
TI  - Identification of colorectal adenomas by a quantitative immunochemical faecal
      occult blood screening test depends on adenoma characteristics, development
      threshold used and number of tests performed.
AB  - BACKGROUND: Faecal occult blood tests (FOBT) are faulted by low sensitivity for
      advanced adenomatous polyps (AAP). Quantified, immunochemical, haemoglobin (Hb)
      specific immunochemical FOBT (I-FOBT) measurements are now used for colorectal
      screening. AIMS: To correlate adenoma characteristics to amount of faecal Hb lost
      and to evaluate sensitivity and specificity for AAP by faecal Hb development
      threshold used and number of I-FOBTs collected. METHODS: Three daily I-FOBTs were
      collected and analysed in 1221 patients scheduled for colonoscopy. Faecal Hb was
      analysed as ngHb/mL of buffer and the highest result related to colonoscopy
      findings. RESULTS: In 1204 patients without cancer, colonoscopy identified
      adenomas in 294, 99 with AAPs. Adenoma patients had elevated faecal Hb increasing
      with advanced histology, size, pedunculated shape and multiplicity (P < 0.001 for
      all). At 50 ngHb/mL threshold, sensitivity and specificity for AAPs were 54.5%
      (95%CI 44.7, 64.7) and 88.1% (95%CI 86.2, 90.1) for three tests. At higher
      thresholds, sensitivity decreased, but was significantly higher with more samples
      collected. Conversely, specificity increased at higher thresholds, but decreased
      with more samples. CONCLUSIONS: Faecal Hb loss from adenomas is significantly
      associated with size, number and advanced features. Sensitivity and specificity
      for AAPs are determined by test threshold chosen and number of samples collected;
      these determine the number of colonoscopies needed for positive tests.

PMID- 19183148
TI  - Review article: hyperammonaemic and catabolic consequences of upper
      gastrointestinal bleeding in cirrhosis.
AB  - BACKGROUND: Upper gastrointestinal (UGI) bleeding in patients with cirrhosis of
      the liver induces hyperammonaemia and leads to a catabolic cascade that
      precipitates life-threatening complications. The haemoglobin molecule is unique
      because it lacks the essential amino acid isoleucine and contains high amounts of
      leucine and valine. UGI bleed therefore presents the gut with protein of very low
      biologic value, which may be the stimulus to induce net catabolism. AIM: To
      describe the hyperammonaemic and catabolic consequences of UGI bleeding in
      cirrhosis. METHODS: A semi-structured literature search was performed using
      PubMed and article references. RESULTS: It has recently been proven that
      ('simulation of ') a UGI bleed in patients with cirrhosis leads to impaired
      protein synthesis that can be restored by intravenous infusion of isoleucine.
      This may have therapeutic implications for the function of rapidly dividing cells
      and short half-life proteins such as clotting factors. Renal and small bowel
      ammoniagenesis were shown to be the most prominent causes for the hyperammonaemia
      that resulted from a UGI bleed. This provides an explanation for the therapeutic
      failure of the current clinical therapies that are aimed at large bowel-derived
      ammonia production. Isoleucine infusion did not diminish renal ammoniagenesis.
      CONCLUSIONS: New pharmacological therapies to diminish postbleeding
      hyperammonaemia should target the altered inter-organ ammonia metabolism and
      promote ammonia excretion and/or increase the excretion of precursors of
      ammoniagenesis, e.g. l-ornithine-phenylacetate.

PMID- 19183149
TI  - Review article: investigational agents for chronic hepatitis C.
AB  - BACKGROUND: The need for effective treatment for chronic hepatitis C infection
      has driven the development of novel antiviral agents that target specific steps
      in the viral replication cycle. AIM: To evaluate the current literature
      concerning investigational agents for chronic hepatitis C virus infection.
      METHODS: Resources used included PubMed, conference proceedings from the American
      and European Liver Associations' meetings 2005-2008 and the National Institute of
      Health's clinical trials website (http://www.clinicaltrials.gov). The focus was
      restricted to investigational agents that have progressed beyond preclinical
      development. RESULTS: Over 50 investigational agents for chronic hepatitis C
      infection are currently in clinical development. Specifically targeted anti-viral
      therapy for HCV (STAT-C) shows great promise with NS3/4a protease inhibitors now
      entering phase 3 programmes. New interferon-alpha and ribavirin formulations aim
      to optimize anti-viral efficacy yet limit toxicity. Other candidates include
      novel immunomodulators and therapeutic vaccines. CONCLUSIONS: A new era of
      therapy for chronic hepatitis C beckons, promising increased cure rates with
      shortened duration of therapy. However, the era will not be without challenges
      including viral resistance, drug toxicity and the need to optimize combination
      therapy in the face of a rapidly evolving therapeutic arsenal.

PMID- 19183150
TI  - Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible
      disease markers in the irritable bowel syndrome and functional dyspepsia.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are
      common functional disorders without defined pathology. Mast cells and eosinophils
      interact with T lymphocytes and may alter enteric nerve and smooth muscle
      function. AIM: To examine mast cell, eosinophil and intraepithelial lymphocyte
      populations in duodenal biopsies of subjects with IBS and FD. METHODS: A random
      sample of an adult Swedish population (n = 1001; mean age 54 years; 51% female)
      underwent upper endoscopy and biopsy; 51 cases with FD and 41 cases with IBS were
      compared with 48 randomly selected controls. Eosinophils were identified by light
      microscopy; mast cells by immunocytochemistry (CD117). Intraepithelial
      lymphocytes were counted per 100 enterocytes. Cell counts were quantified by
      counting the number per high power field (HPF) in 5HPFs in the bulb (D1) and
      second part of duodenum (D2), summed over 5HPFs at each site. RESULTS: Cases and
      controls showed similar demographics. Compared to controls, IELs in IBS
      constipation were significantly increased (P = 0.005). Mast cells were
      significantly increased in IBS in D2 (P < 0.001), while eosinophils were
      significantly increased in FD in D1 and D2 (P < 0.001). CONCLUSION: Duodenal mast
      cell hyperplasia is linked to IBS and eosinophilia to FD, and duodenal biopsy may
      identify subsets of these disorders.

PMID- 19183151
TI  - The views of gastroenterologists about the role of nurse endoscopists, especially
      in colorectal cancer screening.
AB  - BACKGROUND: Nurse endoscopists may provide a solution for the insufficient
      endoscopic capacity in colorectal cancer (CRC) screening. AIM: To determine the
      views of gastroenterologists about the potential role of nurse endoscopists in
      gastrointestinal endoscopy. METHODS: A postal questionnaire was sent to all
      registered gastroenterologists (n = 301) and gastroenterology residents (n = 79)
      in the Netherlands. RESULTS: Two hundred and thirty five of 380 (62%)
      gastroenterologists and residents completed the questionnaire. Overall, 48% were
      positive towards introduction of nurse endoscopists, whereas 18% were neutral and
      34% negative. Respondents expected no major differences in endoscopic quality
      between physicians and nurse endoscopists. Nevertheless, 69% expected that
      patient experiences would be better met by physicians. Multivariate analysis
      showed that actual experience with nurse endoscopists and beliefs that nurse
      endoscopists are able to provide adequate endoscopic quality and good patient
      experiences, were independent predictors for a positive attitude towards
      introduction of nurse endoscopists [OR 6.6 (2.3-18.4), OR 1.9 (1.2-3.5) and OR
      2.1 (1.2-2.9), respectively]. Respectively 89% and 66% of the respondents
      considered sigmoidoscopy and colonoscopy for CRC screening as appropriate
      procedures to be performed by nurse endoscopists. Diagnostic and therapeutic
      endoscopies were considered less appropriate. CONCLUSION: A majority of
      gastroenterologists have a positive attitude towards introduction of nurse
      endoscopists, especially for CRC screening endoscopies.

PMID- 19183152
TI  - Adherence to best practice guidelines in dyspepsia: a survey comparing dyspepsia
      experts, community gastroenterologists and primary-care providers.
AB  - BACKGROUND: Although 'best practice' guidelines for dyspepsia management have
      been disseminated, it remains unclear whether providers adhere to these
      guidelines. AIM: To compare adherence to 'best practice' guidelines among
      dyspepsia experts, community gastroenterologists and primary-care providers
      (PCPs). METHODS: We administered a vignette survey to elicit knowledge and
      beliefs about dyspepsia including a set of 16 best practices, to three groups:
      (i) dyspepsia experts; (ii) community gastroenterologists and (iii) PCPs.
      RESULTS: The expert, community gastroenterologist and PCP groups endorsed 75%,
      73% and 57% of best practices respectively. Gastroenterologists were more likely
      to adhere with guidelines than PCPs (P < 0.0001). PCPs were more likely to define
      dyspepsia incorrectly, overuse radiographic testing, delay endoscopy, treat
      empirically for Helciobacter pylori without confirmatory testing and avoid first
      line proton pump inhibitors (PPIs). PCPs had more concerns about adverse events
      with PPIs [e.g. osteoporosis (P = 0.04), community-acquired pneumonia (P = 0.01)]
      and higher level of concern predicted lower guideline adherence (P = 0.04).
      CONCLUSIONS: Gastroenterologists are more likely than PCPs to comply with best
      practices in dyspepsia, although compliance remains incomplete in both groups.
      PCPs harbour more concerns regarding long-term PPI use and these concerns may
      affect therapeutic decision making. This suggests that best practices have not
      been uniformly adopted and persistent guideline-practice disconnects should be
      addressed.

PMID- 19183153
TI  - Interaction between psychiatric and autoimmune disorders in coeliac disease
      patients in the Northeastern United States.
AB  - BACKGROUND: Previous studies yielded conflicting results regarding the presence
      of an association between coeliac disease (CD) and psychiatric disorders
      including depression. This association has not been studied in the United States.
      AIM: To determine the prevalence of psychiatric and autoimmune disorders in
      patients with CD in the US compared with control groups. METHODS: In a case
      control study, the prevalence of psychiatric and autoimmune disorders was
      compared in 600 CD patients, 200 irritable bowel syndrome (IBS) patients and 200
      healthy controls. RESULTS: The prevalence of depression in CD was 17.2% and was
      similar to that in IBS (18.5%, P = 0.74) and controls (16.0%, P = 0.79). Among CD
      patients, type I diabetes mellitus (DM) was identified as a significant risk
      factor for depression (P < 0.01) with 37% of patients with both CD and type I DM
      having clinical depression. CONCLUSION: The prevalence of depression in CD is
      similar to that in other chronic gastrointestinal diseases and healthy controls.
      However, there is a markedly elevated risk of depression in patients with both
      type I DM and CD. Differing rates of type 1 DM among coeliac populations may
      account for disparity in published rates of depression in patients with CD.

PMID- 19183154
TI  - Predictors of persistence with 5-aminosalicylic acid therapy for ulcerative
      colitis.
AB  - BACKGROUND: Individuals with ulcerative colitis (UC) are at risk for poor
      persistence with therapy. AIM: To identify factors predicting persistence with 5
      aminosalicylic acid (5-ASA) therapy after 3 and 12 months in subjects with UC.
      METHODS: In this retrospective cohort study, persistence with 5-ASA therapy was
      determined from prescription refill data from a commercial health insurance
      claims database. The analysis included subjects with UC who filled a prescription
      for any oral 5-ASA between October 2002 and September 2004. Persistence was
      defined as prescription refill at 3 and/or 12 months. Multivariate logistic
      regression modelling identified variables independently associated with
      persistence at 3 and 12 months. RESULTS: In all, 3574 subjects were identified.
      Fifty-seven per cent (2044) were persistent at 3 months. Glucocorticoid use
      before the index prescription predicted improved persistence at 3 months.
      Psychiatric diagnosis, mail order of the index prescription, female gender and co
      pay predicted decreased persistence. At 12 months, 1124 (55%) remained
      persistent. Rectal 5-ASA use, older age and switching to a different 5-ASA
      predicted improved persistence at 12 months. Hospitalization for a
      gastrointestinal condition, mail order of the 3-month prescription and number of
      co-morbid illnesses predicted lower persistence. CONCLUSION: Persistence with 5
      ASA treatment in UC is complex and multifactorial, and differs by time period.

PMID- 19183155
TI  - Increased health costs from mandated Therapeutic Substitution of proton pump
      inhibitors in British Columbia.
AB  - BACKGROUND: In 2003, British Columbia's PharmaCare programme implemented a drug
      reimbursement policy called Therapeutic Substitution, which required patients
      with acid-related diseases, primarily gastro-oesophageal reflux disease (GERD),
      to make a medically unnecessary switch from their prescribed proton pump
      inhibitor (PPI) to the cheapest available brand name PPI (Pariet, rabeprazole
      sodium), comprising a different (nongeneric) chemical. AIM: To evaluate the
      independent effects of PPI Therapeutic Substitution on individual healthcare
      utilization among those complying with the policy. METHODS: We used the BC
      Ministry of Health Services' individual-level linked data, allowing isolation of
      healthcare utilization for the entire population of PPI consumers from 2002 to
      2005. RESULTS: After controlling for individual case variation in age, gender and
      a proxy for pre-existing health status, regression analysis revealed
      statistically significant greater overall use of PPIs, physician services and
      hospital services independently associated with patients who complied with
      Therapeutic Substitution. Over the 3-year period 2003-2005, this represented net
      healthcare expenditures totalling approximately C$43.51 million (C$9.11 million
      in total PPI drug expenditures, C$24.65 million for physician services and C$9.75
      million for hospital services). CONCLUSION: Medically unnecessary drug switching
      caused by compliance with Therapeutic Substitution policy appears to be
      independently associated with higher overall healthcare utilization.

PMID- 19183156
TI  - Meta-analysis: efficacy of bovine lactoferrin in Helicobacter pylori eradication.
AB  - BACKGROUND: Several randomized-controlled trials (RCTs) have sought to determine
      the efficacy of bovine lactoferrin in Helicobacter pylori eradication with
      equivocal results. AIM: To evaluate the effect of bovine lactoferrin
      supplementation in H. pylori eradication. METHODS: Electronic databases, reviews,
      bibliographies, abstracts and conference proceedings were searched. Included
      trials had to be randomized or quasi-randomized and controlled, using bovine
      lactoferrin in the intervention group, treating Helicobacter-infected subjects
      and evaluating eradication of H. pylori as an outcome. RESULTS: The search
      identified five eligible RCTs (of 169). Data were available for 682 subjects
      (bovine lactoferrin group-n = 316; control group-n = 366). The pooled odds ratio
      (five studies) for eradication by intention-to-treat analysis was 2.22 (95% CI
      1.44-3.44; P = 0.0003) using the fixed effects model (FEM) and 2.24 (95% CI 1.15
      4.35; P = 0.0003) using the random effects model (REM) (Cochran's Q = 6.83; P =
      0.145). The pooled risk difference was 0.11 (95% CI 0.05-0.16; P = 0.0001) by FEM
      (Cochran's Q = 6.67; P = 0.154) and 0.10 (95% CI 0.04-0.17; P = 0.0023) by REM.
      There was no significant difference in incidence of adverse effects. CONCLUSION:
      Bovine lactoferrin potentially improves H. pylori eradication rates without any
      impact on adverse effects, but available evidence is limited and further research
      is necessary to confirm the findings.

PMID- 19183157
TI  - Clinical trials: healing of erosive oesophagitis with dexlansoprazole MR, a
      proton pump inhibitor with a novel dual delayed-release formulation--results from
      two randomized controlled studies.
AB  - BACKGROUND: Dexlansoprazole MR employs a dual delayed-release delivery system
      that extends drug exposure and prolongs pH control compared with lansoprazole.
      AIM: To assess the efficacy and safety of dexlansoprazole MR in healing erosive
      oesophagitis (EO). METHODS: Patients in two identical double-blind, randomized
      controlled trials (n = 4092) received dexlansoprazole MR 60 or 90 mg or
      lansoprazole 30 mg once daily. Week 8 healing was assessed using a closed testing
      procedure--first for non-inferiority, then superiority, vs. lansoprazole.
      Secondary endpoints included week 4 healing and week 8 healing in patients with
      moderate-to-severe disease (Los Angeles Classification grades C and D). Life
      table and crude rate analyses were performed. Symptoms and tolerability were
      assessed. RESULTS: Dexlansoprazole MR achieved non-inferiority to lansoprazole,
      allowing testing for superiority. Using life-table analysis, dexlansoprazole MR
      healed 92-95% of patients in individual studies vs. 86-92% for lansoprazole; the
      differences were not statistically significant (P > 0.025). Using crude rate
      analysis, dexlansoprazole MR 90 mg was superior to lansoprazole in both studies
      and 60 mg was superior in one study. Week 4 healing was > 64% with all treatments
      in both studies. In an integrated analysis of 8-week healing in patients with
      moderate-to-severe EO, dexlansoprazole MR 90 mg was superior to lansoprazole. All
      treatments effectively relieved symptoms and were well tolerated. CONCLUSION:
      Dexlansoprazole MR is highly effective in healing EO and offers benefits over
      lansoprazole, particularly in moderate-to-severe disease.

PMID- 19183158
TI  - Clinical course of hepatitis B virus infection during pregnancy.
AB  - BACKGROUND: For women with hepatitis B virus (HBV) infection, little is known
      about the natural progression of the disease during pregnancy or its impact on
      pregnancy outcomes. OBJECTIVES: To investigate the natural progression of HBV
      infection during pregnancy or its impact on pregnancy outcomes. METHODS: In this
      retrospective cohort study, we reviewed medical records of all patients who were
      pregnant and presented with HBsAg-positivity between 2000 and 2008 at a community
      gastroenterology practice and a university hepatology clinic. Maternal
      characteristics were analysed according to maternal and perinatal outcomes.
      RESULTS: A total of 29 cases with at least 2 measurements of either HBV DNA or
      alanine aminotransferase (ALT) levels were included. Older age was the only
      predictor of a trend towards higher risk of an adverse clinical outcome [OR =
      1.21 (0.97-1.51), P = 0.089], defined as either a negative foetal outcome
      (premature delivery, spontaneous abortion), or a negative maternal outcomes
      (gestational diabetes mellitus, pre-eclampsia, hepatic flare, liver failure).
      This trend for age remained even after adjusting for baseline ALT. Baseline serum
      HBV DNA, ALT, hepatitis B e antigen status, gravida and parity were not
      significant predictors for adverse clinical outcomes. Four patients developed
      liver failure. CONCLUSIONS: Maternal and neonatal outcomes are highly variable in
      this clinic-based patient cohort. Severe complications due to HBV infection can
      occur during pregnancy in previously asymptomatic patients. It is unclear how
      generalizable the results observed in this cohort would be to the general
      population; therefore, further studies are needed to identify reliable predictors
      for significant adverse outcomes and until more data are available, pregnant
      patients with HBV infection should be monitored with periodic serum HBV DNA and
      ALT levels.

PMID- 19183160
TI  - Time trends in peptic ulcer, erosive reflux oesophagitis, gastric and oesophageal
      cancers in a multiracial Asian population.
AB  - BACKGROUND: Dramatic changes in the prevalence and pattern of gastrointestinal
      disease has taken place in Asia in recent years. AIM: To compare the prevalence
      of duodenal (DU) and gastric ulcers (GU), erosive oesophagitis (EO), gastric
      cancer (GCA) and oesophageal cancer (OCA) and Helicobacter pylori infection over
      a 10-year interval of time in a multiracial South-East Asian population. METHODS:
      Endoscopy records of first time gastroscopy in the University of Malaya Medical
      Centre, Kuala Lumpur, Malaysia were reviewed for 1989/1990 and 1999/2000.
      RESULTS: In the period of 1989-1990, 3252 records and in 1999-2000, 4615 records
      were analysed. Both DU (21.1-9.5%) and GU (11.9-9.4%) had decreased significantly
      (P < 0.001). EO had increased significantly from 2.0% to 8.4% (P < 0.001). Both
      GCA and OCA had declined in the 10-year interval. Helicobacter pylori prevalence
      had decreased from 51.7% to 30.3% (P < 0.001).The decrease in DU and GU was seen
      in all racial groups. The increase in EO was most marked in Indians and the
      decrease in GCA in Chinese. The proportion of H. pylori-associated DU and GU had
      also decreased with time. CONCLUSIONS: Peptic ulcers and H. pylori infection had
      declined over a 10-year period of time and showed an opposing time trend with EO,
      which had increased dramatically. Both GCA and OCA had declined in prevalence.

PMID- 19183161
TI  - Meta-analysis: the efficacy and safety of certolizumab pegol in Crohn's disease.
AB  - BACKGROUND: Certolizumab pegol is the third anti-TNF-alpha agent approved by the
      Food and Drug Administration of the United States. AIM: To provide a
      comprehensive up-to-date review of the efficacy and safety of certolizumab in
      Crohn's disease (CD). METHODS: Electronic databases, including PubMed, EMBASE,
      the Cochrane library and the Science Citation Index, were searched to retrieve
      relevant trials. In addition, meeting abstracts and the reference lists of
      retrieved articles were reviewed for further relevant studies. RESULTS: Three
      trials, enrolling a total of 1040 patients, are included in the meta-analysis to
      evaluate the short-term efficacy of certolizumab, which is effective for rapid
      induction and long-term maintenance of clinical response or remission and can
      improve quality of life in patients with Crohn's disease. Certolizumab is also
      effective for patients who have lost response to infliximab. However, its
      efficacy in infliximab-exposed patients is probably less than in infliximab-naive
      patients. Re-induction with certolizumab in patients who have flared on
      maintenance therapy can rescue a significant proportion of patients. There is no
      significant association between the efficacy of certolizumab and the baseline C
      reactive protein level. In comparison with placebo, certolizumab does not
      increase the risk of serious adverse events. CONCLUSIONS: Certolizumab is
      effective and safe in treating Crohn's disease. Further studies are still
      required to assess its full safety profile.

PMID- 19183162
TI  - A randomized, placebo-controlled study of the effects of naproxen, aspirin,
      celecoxib or clopidogrel on gastroduodenal mucosal healing.
AB  - BACKGROUND: Many individuals with gastroduodenal ulcers require on-going, non
      steroidal anti-inflammatory drug (NSAID) or anti-platelet therapy. AIMS: To
      evaluate the effects of these agents on gastroduodenal mucosal healing. METHODS:
      Helicobacter pylori-negative volunteers were randomized to receive naproxen,
      celecoxib, aspirin, clopidogrel or placebo. Antral and duodenal lesions were
      created endoscopically with a biopsy forceps. After 7 days of medication dosing,
      each lesion was scored [from 0 (low) to 8 (high)] using a validated methodology.
      The primary endpoint was the mean injury score. The secondary endpoint was the
      percentage of subjects with > or = 1 unhealed lesion. RESULTS: In all, 108
      subjects completed the study. Naproxen impaired antral lesion healing more than
      placebo, clopidogrel, aspirin or celecoxib (mean injury score of 4.3 vs. 3.0,
      2.7, 3.2, and 3.2, respectively, P < 0.05). Naproxen impaired duodenal lesion
      healing more than placebo, clopidogrel or aspirin (mean injury score of 4.0 vs.
      2.4, 2.6, and 2.2, respectively, P < 0.05). More subjects taking naproxen than
      placebo or clopidogrel had > or =1 unhealed antral lesions (72.2% vs. 36.0% and
      32.0%, respectively, P < 0.05) and unhealed duodenal lesions (61.1% vs. 16.0% and
      28.0%, respectively, P < 0.05). CONCLUSIONS: Naproxen may impair gastroduodenal
      healing more than aspirin or celecoxib in H. pylori negative subjects.
      Clopidogrel did not impair mucosal healing.

PMID- 19183163
TI  - Infliximab dependency in children with Crohn's disease.
AB  - BACKGROUND: Recently, infliximab dependency has been described. AIM: To assess
      frequency of ID in 82 consecutive Crohn's disease children treated with
      infliximab 2000-2006 and to describe clinical and genetic predictors of long-term
      infliximab response. METHODS: A phenotype model of infliximab dependency was used
      to assess treatment response: 'immediate outcome' (30 days after infliximab
      start)--complete/partial/no response. 'Long-term outcome': (i) prolonged
      response: maintenance of complete/partial response; (ii) infliximab dependency:
      relapse < or = 90 days after intended infliximab cessation requiring repeated
      infusions to regain complete/partial response or need of infliximab >12 months to
      sustain response. Polymorphisms TNF-308 A>G, TNF-857 C>T, Casp9 93 C>T, FasL-844
      C>T, LTA 252 C>T and CARD15 (R702W, G908R, 1007fs) were analysed. RESULTS: Ninety
      four per cent of children obtained complete/partial response. In long-term
      outcome, 22% maintained prolonged response, 12% had no response, while 66% became
      infliximab dependent. Perianal disease and no previous surgery were associated
      with infliximab dependency (OR 5.34, 95% CI: 1.24-22.55; OR 6.7, 95% CI: 1.67
      26.61). No association was found with studied polymorphisms. The cumulative
      probability of surgery 50 months after starting infliximab was 10% in infliximab
      dependency, 30% in prolonged responders and 70% in nonresponders (P = 0.0002).
      CONCLUSIONS: Sixty-six per cent of children became infliximab dependent. Perianal
      disease and no surgery prior to infliximab were associated with infliximab
      dependency phenotype.

PMID- 19183164
TI  - Randomized double-blind, placebo-controlled trial of sublingual immunotherapy
      with a Pru p 3 quantified peach extract.
AB  - BACKGROUND: Peach allergy is highly prevalent in the Mediterranean area; it is
      persistent and potentially severe, and therefore a prime target for
      immunotherapy. We aimed to study the efficacy and safety of sublingual
      immunotherapy (SLIT) with a peach extract quantified in mass units for Pru p 3,
      the peach lipid transfer protein. METHODS: Randomized, double-blind, placebo
      controlled (DBPC) clinical trial. The main efficacy outcome was the change in the
      response to a DBPC food challenge (DBPCFC) with peach. Secondary efficacy
      outcomes were the changes in skin prick test (SPT), and in specific
      immunoglobulin E (IgE) and IgG(4) to Pru p 3. Tolerance was assessed with a
      careful recording of adverse events. RESULTS: After 6 months of SLIT, the active
      group tolerated a significantly higher amount of peach (three- to ninefold),
      presented a significant decrease (5.3 times) in SPT, and a significant increase
      in IgE and IgG(4) to Pru p 3. No significant changes were observed within the
      placebo group. Statistically significant inter-group differences were only
      observed in the SPT and IgG(4) responses. No serious adverse events were
      reported. Systemic reactions were mild, and observed with a similar frequency in
      both groups. Local reactions were significantly more frequent in the active group
      (three times) and 95% of them restricted to the oral cavity. CONCLUSION: In this
      first exploratory clinical trial, SLIT for peach allergy seems to be a promising
      therapeutic option that could modify the clinical reactivity of the patients to
      peach intake and the underlying immunological response with a good tolerance.

PMID- 19183165
TI  - Time trends in prevalence and severity of childhood asthma and allergies from
      1995 to 2002 in France.
AB  - OBJECTIVE: To assess time trends in symptoms of asthma, allergic rhinitis and
      atopic eczema among adolescents in Languedoc Roussillon, France. METHODS: Two
      cross-sectional surveys were conducted 7 years apart using the same protocol.
      School-based samples of 3383 participants in the 1995 survey and 1642
      participants in the 2002 survey respectively were recruited. RESULTS: There was a
      tendency towards stagnation in current symptoms of asthma, rhinoconjunctivitis
      and eczema. Indices related to lifetime diagnosis of asthma, hay fever and eczema
      increased. For all the conditions, indices of severity also showed a decrease in
      the 7-year study period. CONCLUSIONS: Our study shows that symptoms of asthma,
      allergic rhinitis and eczema were stable, supporting the effectiveness of
      national asthma prevention and management guidelines for such diseases. The
      increase in indices related to lifetime diagnosis could be the result of
      increased public and professional awareness of the diseases and changes in
      diagnostic labelling in recent years.

PMID- 19183166
TI  - Adherence rate to inhaled corticosteroids and their impact on asthma control.
AB  - BACKGROUND: Poor asthma control is associated to high morbidity. The objective of
      this study was to assess the association between adherence rates to
      beclomethasone dipropionate (BDP) and the degree of asthma control. METHODS: A
      cohort concurrent study was carried out for 12 months with 122 asthmatic
      patients, aged 3-12 years, randomly selected in a pediatric pulmonology
      outpatient clinic, who received BDP free of charge. Adherence rates were verified
      by pharmacy records. Clinical control was assessed through a scoring system
      comprised four variables (nocturnal and morning symptoms, limitation of physical
      activities and exacerbations). Total score was 16 points. Patients whose score
      was below or equal to two were considered controlled (group 1), and patients
      whose score was above or equal to three were considered uncontrolled (group 2).
      For patients able to perform spirometry, we considered as controlled the patients
      with forced expiratory volume in 1 s (FEV(1)) equal to or above 80% of the
      predicted value, and as uncontrolled the patients with FEV(1) below 80%. RESULTS:
      Fewer than half (40.3% maximum) of the 122 patients maintained asthma control.
      Median adherence rate of groups 1 and 2 were 85.5% and 33.8%, (P < 0.001) in the
      4th month, 90.0% and 48.0% (P < 0.001) in the 8th month and 84.4% and 47.0% in
      the 12th month (P < 0.001), respectively. CONCLUSION: In all periods, there were
      statistically significant differences in adherence rates for maintaining or not
      maintaining the asthma control. Optimal asthma control entailed adherence rate
      higher than 80%. Strategies for reducing asthma morbidity should include a
      regular monitoring of adherence to inhaled steroids.

PMID- 19183167
TI  - Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a
      potential marker to predict response.
AB  - BACKGROUND: Recent findings have raised new interests about the use of
      anticholinergics, especially tiotropium, for the treatment of asthma. This study
      was performed to determine whether an additional improvement in lung function is
      obtained when tiotropium is administrated in addition to conventional therapies
      in severe asthmatics, and to identify factors capable of predicting the response
      to tiotropium, using a pharmacogenetic approach. METHODS: A total of 138 severe
      asthmatics on conventional medications and with decreased lung function were
      randomly recruited. Tiotropium 18 microg was added once a day and lung functions
      were measured every 4 weeks. Responders were defined as those with an improvement
      of > or = 15% (or 200 ml) in the forced expiratory volume in 1 s (FEV1) that was
      maintained for at least 8 successive weeks. Eleven single nucleotide
      polymorphisms (SNPs) in CHRM1-3 (coding muscarinic receptors one to three) which
      were identified by re-sequencing, and Arg16Gly and Gln27Glu in ADRB2 (coding
      beta(2) adrenoreceptor) were scored in 80 of the 138 asthmatics. RESULTS: Forty
      six of the 138 asthmatics (33.3%) responded to tiotropium treatment. Logistic
      regression analyses (controlled for age, gender, and smoking status) showed that
      Arg16Gly in ADRB2 [P = 0.003, OR (95% CI) = 0.21 (0.07-0.59) in a minor allele
      dominant model] was significantly associated with response to tiotropium.
      CONCLUSIONS: As many as 30% of severe asthmatics on conventional medications with
      reduced lung function were found to respond to adjuvant tiotropium. The presence
      of Arg16Gly in ADRB2 may predict response to tiotropium.

PMID- 19183168
TI  - Time course for development of psoralen plus ultraviolet A erythema following
      oral administration of 5-methoxypsoralen.

PMID- 19183169
TI  - How not to get scar(r)ed: pointers to the correct diagnosis in patients with
      suspected primary cicatricial alopecia.
AB  - Primary cicatricial alopecias (PCAs) are a rare, but important, group of
      disorders that cause irreversible damage to hair follicles resulting in scarring
      and permanent hair loss. They may also signify an underlying systemic disease.
      Thus, it is of paramount importance that clinicians who manage patients with hair
      loss are able to diagnose these disorders accurately. Unfortunately, PCAs are
      notoriously difficult conditions to diagnose and treat. The aim of this review is
      to present a rational and pragmatic guide to help clinicians in the professional
      assessment, investigation and diagnosis of patients with PCA. Illustrating
      typical clinical and histopathological presentations of key PCA entities we show
      how dermatoscopy can be profitably used for clinical diagnosis. Further, we
      advocate the search for loss of follicular ostia as a clinical hallmark of PCA,
      and suggest pragmatic strategies that allow rapid formulation of a working
      diagnosis.

PMID- 19183170
TI  - Nickel allergy as risk factor for hand eczema: a population-based study.
AB  - BACKGROUND: In population-based studies using self-reported nickel allergy, a
      hand eczema prevalence of 30-43% has been reported in individuals with nickel
      allergy. In a previous Swedish study, 958 schoolgirls were patch tested for
      nickel. In a questionnaire follow up 20 years later no association was found
      between nickel allergy and hand eczema. OBJECTIVES: To investigate further the
      relation between nickel allergy and hand eczema. METHODS: Three hundred and sixty
      nine women, still living in the same geographical area, now aged 30-40 years,
      were patch tested and clinically investigated regarding hand eczema. RESULTS:
      Patch testing showed 30.1% nickel-positive individuals. The adjusted prevalence
      proportion ratio (PPR) for hand eczema after age 15 years in relation to nickel
      patch test results was 1.03 (95% confidence interval, CI 0.71-1.50). A history of
      childhood eczema was reported by 35.9%, and the PPR for hand eczema in relation
      to childhood eczema was 3.68 (95% CI 2.45-5.54). When analysing the relation
      separately in women with and without a history of childhood eczema a statistical
      interaction was found. The hand eczema risk was doubled in nickel-positive women
      without a history of childhood eczema, with a PPR of 2.23 (95% CI 1.10-4.49) for
      hand eczema after age 15 years. CONCLUSIONS: A doubled risk for hand eczema was
      found in nickel-positive women without a history of childhood eczema. When
      analysing all participants, there was no statistically significant difference
      between nickel-positive and nickel-negative women regarding occurrence of hand
      eczema. The most important risk factor for hand eczema was childhood eczema. The
      risk for hand eczema in nickel-positive women may previously have been
      overestimated.

PMID- 19183171
TI  - In vivo thickness measurement of basal cell carcinoma and actinic keratosis with
      optical coherence tomography and 20-MHz ultrasound.
AB  - BACKGROUND: Accurate assessment of tumour size is important when planning
      treatment of nonmelanoma skin cancer (NMSC). Imaging with optical coherence
      tomography (OCT) has the potential to diagnose and measure depth of NMSC.
      OBJECTIVES: To compare accuracy of mean tumour thickness measurement in NMSC
      tumours < 2 mm of depth using OCT and 20-MHz high-frequency ultrasound (HFUS). In
      addition, OCT morphology of NMSC was studied in OCT images and the influence of
      histological and colorimetric values on the quality and penetration depth in OCT
      images was estimated. METHODS: In total, 93 patients were scanned and 34 lesions
      [23 basal cell carcinoma (BCC) and 11 actinic keratosis (AK) lesions] < 2 mm
      thick and easily identified in OCT images were studied. OCT and HFUS were
      compared with biopsies. The influence of skin pigmentation and infiltration
      analgesia on OCT image quality was studied. Skin colour was measured with a
      colorimeter. RESULTS: OCT presented narrower limits of agreement than HFUS. Both
      methods overestimated thickness but OCT was significantly less biased (0.392 mm
      vs. 0.713 mm). No relation between OCT penetration depth and skin colour was
      found. CONCLUSIONS: OCT appears more precise and less biased than HFUS for
      thickness measurement in AK and BCC lesions < 2 mm, but both OCT and especially
      HFUS tended to overestimate tumour thickness.

PMID- 19183173
TI  - Cytoplasmic beta-catenin is lacking in a subset of melanoma-associated naevi, but
      is detectable in naevus-associated melanomas: potential implications for melanoma
      tumorigenesis?
AB  - BACKGROUND: An excess of intracellular beta-catenin protein is triggered by
      various genetic alterations in melanoma cell lines, and has been suggested to
      play a role in melanoma tumorigenesis. OBJECTIVES: To investigate the role played
      in vivo by beta-catenin in melanoma tumorigenesis, we compared the cytoplasmic
      detection of beta-catenin in benign melanocytic cells vs. malignant melanoma
      cells presumably generated from these benign melanocytic cells. For this purpose,
      melanocytic naevi occurring in association with melanoma, which were suggested to
      be melanoma precursors, were compared with their associated melanoma for beta
      catenin cytoplasmic immunoreactivity. METHODS: Fifty-seven consecutive cases of
      primary cutaneous melanoma were considered, and 15 of them were found to be
      associated with a melanocytic naevus portion. The naevus portion showed features
      of acquired melanocytic naevus (total 12 cases: five dysplastic, seven
      intradermal) or congenital growth pattern naevus (total three cases: one
      superficial, two deep). All specimens were immunohistochemically investigated for
      beta-catenin. RESULTS: Virtually all primary cutaneous melanomas, including those
      associated with a naevus portion, showed cytoplasmic beta-catenin positivity.
      However, the intradermal naevus portion was consistently cytoplasmic beta-catenin
      negative, while both the dysplastic and the congenital naevus portions were
      cytoplasmic beta-catenin positive. CONCLUSIONS: Beta-catenin excess may play a
      role in melanoma tumorigenesis, because beta-catenin cytoplasmic reactivity was
      found in primary cutaneous melanoma but not in its associated intradermal naevus
      precursor. As, however, beta-catenin cytoplasmic reactivity was detected not only
      in primary cutaneous melanoma but also in its associated dysplastic/congenital
      naevus precursors, beta-catenin stabilization alone is not sufficient to play a
      decisive role for melanoma onset.

PMID- 19183174
TI  - Wilms tumour as a possible early manifestation of hereditary leiomyomatosis and
      renal cell cancer?

PMID- 19183175
TI  - A preliminary investigation into the effect of exposure of photosensitive
      individuals to light from compact fluorescent lamps.
AB  - BACKGROUND: Compact fluorescent lamps (CFLs) are due to replace common
      incandescent lamps over the next few years. There has been no investigation of
      the possible effect of this on patients with photosensitive disorders.
      OBJECTIVES: To determine the effect of exposure of photosensitive individuals to
      light from CFLs. METHODS: The spectral emission from a sample of CFLs was
      measured using a calibrated spectroradiometer. The erythemal response was
      determined in one normal individual and four photosensitive individuals by direct
      exposure of the skin to light from a CFL. The susceptibility of a wider group of
      photosensitive individuals was predicted based on the light dose known to elicit
      a reaction during phototesting at discrete ultraviolet (UV) wavelengths. RESULTS:
      CFLs emit UV radiation at wavelengths down to 254 nm. Prolonged exposure of a
      normal individual's skin produced erythema. However, an exposure of only 2.5 min
      at 5 cm elicited marked erythema in one of the abnormally photosensitive
      patients. CONCLUSIONS: CFLs could be a source of harmful UV radiation to
      photosensitive individuals. Patients with chronic actinic dermatitis are thought
      to be at greatest risk. The use of a protective envelope is recommended.

PMID- 19183176
TI  - A case of primary cutaneous diffuse large B-cell lymphoma, leg type monitored
      with fluorine-18-fluorodeoxyglucose positron emission tomography/computed
      tomography.

PMID- 19183177
TI  - Stromal cell-derived factor 1 expression in various skin tumours.

PMID- 19183178
TI  - In vivo confocal laser scanning microscopy in the diagnosis of melanocytic skin
      tumours.
AB  - Melanoma of the skin represents one of the greatest challenges in early or
      preventive detection. Whereas surgical excision in early stages of melanoma
      development is almost always curative, delayed recognition puts the patient at
      risk for destructive growth and death from disease once the tumour has progressed
      to competence for metastasis. The worldwide introduction of dermoscopy has led to
      improved diagnostic accuracy for melanocytic skin tumours. Whereas dermoscopy has
      probably reached the method's inherent potential diagnostic accuracy because of
      the lack of cellular level evaluation, further improvements could be expected by
      in vivo confocal laser scanning microscopy. In vivo confocal microscopy
      represents a novel imaging tool that allows the noninvasive examination of skin
      cancer morphology in real time at a 'quasihistopathological' resolution viewing
      microanatomical structures and individual cells. Numerous morphological confocal
      features of melanocytic skin tumours have been described and histopathological
      correlates of confocal structures have been previously elucidated. Recently,
      several studies have evaluated the diagnostic accuracy of in vivo confocal
      microscopy for melanocytic skin tumours, investigating approximately 50,000
      tumour images. Remarkably, sensitivity superior to the diagnostic accuracy
      achieved with dermoscopy could be reached by this imaging modality. These studies
      represent a significant contribution to the body of research necessary for the
      evaluation and implementation of in vivo confocal microscopy in clinical practice
      to avoid many currently unnecessary biopsies. In vivo confocal microscopy
      probably augurs a sea change in the way we evaluate melanocytic skin tumours in
      the future and will ultimately move the art of histological diagnosis closer to
      the bedside.

PMID- 19183179
TI  - New-onset psoriasis in a patient treated with interferon beta-1a.

PMID- 19183180
TI  - Comparison of patients with and without digital ulcers in systemic sclerosis:
      detection of possible risk factors.
AB  - BACKGROUND: Digital ulcers (DU) are a major complication in the course of
      systemic sclerosis (SSc). In recent years, efficacious, but expensive therapies
      (e.g. iloprost, sildenafil, bosentan) have been shown to improve healing or to
      reduce the recurrence of DU. For optimal management it would be useful to
      identify the risk factors for DU. Such statistical analyses have been rare
      because they require a high number of patients. OBJECTIVES: To identify potential
      risk factors for DU in patients with SSc. METHODS: We used the registry of the
      German Network for Systemic Scleroderma and evaluated the data of 1881 patients
      included by August 2007. We assessed potential risk factors for DU by comparing
      patients with (24.1%) and without active DU at time of entry (75.9%). RESULTS:
      Multivariate analysis revealed that male sex, presence of pulmonary arterial
      hypertension (PAH), involvement of the oesophagus, diffuse skin sclerosis (only
      when PAH was present), anti-Scl70 antibodies, young age at onset of Raynaud's
      phenomenon (RP), and elevated erythrocyte sedimentation rate (ESR) significantly
      impacted on the appearance of DU. Certain combinations increased the patients'
      probability of presenting with DU, with the highest probability (88%) for male
      patients with early onset of RP, ESR>30 mm h(-1), anti-Scl70 antibodies and PAH.
      Patients with DU developed RP, skin sclerosis and organ involvement approximately
      2-3 years earlier than patients without DU. CONCLUSIONS: The results reveal
      possible risk factors for the occurrence of DU in SSc. As DU are prone to local
      complications, prophylactic vasoactive treatment for patients presenting with
      these factors may be justified.

PMID- 19183182
TI  - Shrinkage of skin excision specimens: formalin fixation is not the culprit.
AB  - BACKGROUND: Discrepancies between cutaneous specimen sizes reported by the
      dermatosurgeon and the pathologist are important to evaluate because of their
      legal implications for malignant tumours and the downcoding of surgical acts.
      OBJECTIVES: The objective of this study was to determine the magnitude of changes
      in size and the factors influencing the retraction of routine skin excision
      specimens. METHODS: Three measurements of 82 skin excision specimens--consisting
      of length and width of the planned surgical excision (in vivo), length, width and
      depth of the specimens following excision (ex vivo) and of the specimens after
      formalin fixation (in vitro)--were performed and compared using a nonparametric
      paired test. Factors (age, sex, type and location of the lesions and initial
      measures) that could influence the amount of shrinkage were analysed using
      multiple linear regression models. RESULTS: The mean in vivo to in vitro
      shrinkage was 16% for length and 18% for width (P<0.001). The shrinkage was
      significant between in vivo and ex vivo measures (P<0.001), while no difference
      was observed between ex vivo to in vitro measures. In multivariate analysis,
      length shrinkage increased significantly with initial length (regression
      coefficient of 0.24, P=0.001) and limb location (1.25, P=0.048), and decreased
      significantly with initial width (-0.19, P=0.016). After adjusting for initial
      width, width shrinkage was neither significantly associated with type of lesion
      (malignant or not, P=0.20), nor with location (P=0.35). CONCLUSIONS: Shrinkage of
      skin excision specimens occurred immediately after surgical excision and prior to
      formalin fixation. Patients' age, sex and type of skin lesion did not influence
      the amount of shrinkage. Length shrinkage was more important for specimens
      excised from the extremities and increased with initial length and smaller width.

PMID- 19183181
TI  - Ichthyosis vulgaris: novel FLG mutations in the German population and high
      presence of CD1a+ cells in the epidermis of the atopic subgroup.
AB  - BACKGROUND: Ichthyosis vulgaris (IV) is a genetic disorder with a prevalence of
      1:250-1000 caused by filaggrin (FLG) mutations, which also predispose to atopic
      diseases. OBJECTIVES: To study the genotype/phenotype relationship in IV and to
      analyse whether the suggested skin barrier defect is associated with differences
      of epidermal dendritic cells. PATIENTS/METHODS: We evaluated a cohort of 26
      German patients with IV, established an IV severity score and analysed epidermal
      ultrastructure, histology, filaggrin and CD1a antigens. Mutations were screened
      by restriction enzyme analysis. Particular sequencing techniques allowed the
      complete FLG analysis to reveal novel mutations. RESULTS: The combined null
      allele frequency of R501X and 2282del4 was 67.3%. Patients also showed the
      mutations S3247X and R2447X as well as five novel FLG mutations: 424del17 and
      621del4 (profilaggrin S100 domain), 2974delGA (repeat 2), R3766X (repeat 10(1))
      and E4265X (repeat 10(2)). Their combined allele frequency in controls was <0.7%.
      No mutation was found in one IV patient, all in all approximately 27% were
      heterozygous, and the majority (approximately 69%) showed two null alleles. The
      IV severity score and ultrastructure showed a significant correlation with
      genotypes. Interestingly, CD1a cell counts showed a significant difference
      between nonatopic and atopic IV patients both with eczema and without eczema.
      CONCLUSIONS: We confirm that the mutations R501X and 2282del4 represent the most
      frequent genetic cause in German IV patients. The novel mutations are probably
      population and family specific. The observed differences of CD1a cells support
      the hypothesis that there is a barrier defect that predisposes to atopic
      manifestations, possibly independent of atopic eczema.

PMID- 19183183
TI  - How should we determine length of anticoagulation after proximal deep vein
      thrombosis of the lower limbs?
AB  - The current approach for deciding the duration of vitamin K antagonist (VKA)
      treatment after an episode of venous thrombo-embolism (VTE) is mainly based on
      the characteristic of the index event (3 months or longer in case of
      unknown/persistent risk factors, 3 months or less in case of removable causes).
      However, the length of anticoagulation should be tailored on the patient's risk
      for recurrent thrombosis as well as for bleeding, but such 'time for decision' is
      often unclear and the optimal duration of VKA remains debatable. The presence of
      persistent residual vein thrombosis and increased D-dimer levels after stopping
      therapy are predictors for recurrent deep vein thrombosis (DVT). Management
      strategies based on these parameters have been demonstrated to optimize the
      decision for VKA duration, as they establish the patient's intrinsic risk for
      recurrent events. This annotation discusses current practice and upcoming
      approaches regarding the length of VKA treatment after a first episode of DVT.

PMID- 19183184
TI  - An eosinophilic pseudotumour in the liver.

PMID- 19183185
TI  - Relationship between HLA-DP supertype and survival in childhood acute
      lymphoblastic leukaemia: evidence for selective loss of immunological control of
      residual disease?
AB  - We recently reported that two of six HLA-DP supertypes (DP1-4, 6, 8) were
      associated with susceptibility (DP2) and resistance (DP1) to childhood acute
      lymphoblastic leukaemia (ALL). To determine whether DP supertypes are associated
      with childhood ALL prognosis, we compared treatment outcomes in a cohort (n =
      798) of DPB1-typed ALL cases in the UK Medical Research Council UKALL XI trial.
      No differences in clinical characteristics and outcome between DPB1-typed and
      untyped (n = 1292) cases suggest no selection bias. Event-free survival (EFS)
      rates in patients with DP1 and DP3 supertypes were significantly worse than in
      patients with DP2, DP4, DP6 and DP8 [10-year EFS: 55%; 95% confidence interval
      (CI) = 49-61%; compared with 64% (61-68%), P = 0.006]. Ten-year EFS in DP1/DP3
      heterozygous patients [30% (2-58%)] was significantly worse than in patients with
      DP1, DP3 or neither allele [56% (50-62%); P = 0.02]. Lack of evidence that DP1 or
      DP3 are associated with known prognostic factors leads us to suggest that these
      two supertypes exert an independent effect on prognosis. This may involve
      abrogation of DP1/3-restricted T-cell control of residual disease due to
      selective effects of chemotherapy. Further studies of HLA supertypes in relation
      to outcome in recent childhood ALL trials may resolve this question.

PMID- 19183186
TI  - Bis(1H-indol-2-yl)methanones are effective inhibitors of FLT3-ITD tyrosine kinase
      and partially overcome resistance to PKC412A in vitro.
AB  - Inhibition of the mutated fms-like tyrosine kinase 3 (FLT3) receptor tyrosine
      kinase is a promising therapeutic strategy in acute myeloid leukaemia (AML).
      However, development of resistance to FLT3 tyrosine kinase inhibitors (TKI), such
      as PKC412A, has been described recently. This observation may have an increasing
      impact on the duration of response and relapse rates in upcoming clinical trials
      employing FLT3-TKI. Herein we investigated two representatives of a novel class
      of FLT3-TKI: Bis(1H-indol-2-yl)methanones. Both compounds effectively induced
      apoptosis in FLT3-internal tandem duplicate (ITD)-transfected murine myeloid
      cells and in primary FLT3-ITD positive blasts. Combination of both compounds with
      chemotherapy revealed synergistic effects in apoptosis assays. The compounds did
      not show significant toxicity in human bone marrow cells derived from healthy
      donors. Compound102 overcame resistance to PKC412 within a non-myelotoxic dose
      range. Western Blotting experiments of 32D-FLT3-ITD cells showed dose-dependent
      dephosphorylation of FLT3-ITD and of its downstream targets STAT5, AKT and ERK
      upon incubation with either compound. In conclusion, bis(1H-indol-2-yl)methanones
      overcome resistance mediated by FLT3-ITD mutations at position N676 and show
      strong efficacy in FLT3-ITD-positive cells alone as well as in combination with
      chemotherapy. We propose that further development of methanone compounds
      overcoming resistance to currently established FLT3-TKIs is an important step
      forward to an anticipated need within our future therapeutic algorithm in FLT3
      ITD-positive AML.

PMID- 19183187
TI  - Splenectomy in sickle cell anaemia: a cause of further crises?

PMID- 19183189
TI  - Microangiopathic haemolytic anaemia in a patient with metastatic breast cancer.

PMID- 19183188
TI  - Recent developments in the understanding of the combined deficiency of FV and
      FVIII.
AB  - Combined deficiency of factor V (FV) and factor VIII (FVIII) (F5F8D) is a genetic
      disorder characterized by mild-to-moderate bleeding and coordinate reduction in
      plasma FV and FVIII levels, as well as platelet FV level. Recent studies
      identified mutations in two genes (LMAN1 and MCFD2) as the cause of F5F8D. Though
      clinically indistinguishable, MCFD2 mutations generally exhibit lower levels of
      FV and FVIII than LMAN1 mutations. LMAN1 is a mannose-specific lectin that cycles
      between the endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment.
      MCFD2 is an EF-hand domain protein that forms a calcium-dependent heteromeric
      complex with LMAN1 in cells. Missense mutations in the EF-hand domains of MCFD2
      abolish the interaction with LMAN1. The LMAN1-MCFD2 complex may serve as a cargo
      receptor for the ER-to-Golgi transport of FV and FVIII, and perhaps a number of
      other glycoproteins. The B domain of FVIII may be important in mediating its
      interaction with the LMAN1-MCFD2 complex.

PMID- 19183190
TI  - Influence of bone marrow graft B lymphocyte subsets on outcome after HLA
      identical sibling transplants.
AB  - The potential role of the infused B cell subset after Hematopoietic Stem Cell
      Transplantation has not been yet studied. The present study analyzed the impact
      of B cells on transplant outcome in 254 patients who received a bone marrow graft
      from a human leucocyte antigen-identical sibling donor. The influence of B
      lineage-specific hematopoietic progenitor cells (CD34(+) CD19(+)) and B cells
      (immature and mature B cells, CD34(-) CD19(+)) was also analyzed. All included
      patients received a myeloablative regimen. The cumulative incidence function of
      acute graft-versus-host (GvHD) grade II to IV was 48% and was inversely
      associated with the number of CD34(+) CD19(+). There were no statistically
      significant associations between B cell subsets and chronic GvHD or survival. The
      CD34(+) CD19(+) B cell subset remained significantly associated with acute GvHD
      in multivariate analysis (Relative risk = 0.32, 95% confidence interval: 0.11
      0.92, P = 0.035). In conclusion, a higher B lineage-specific hematopoietic
      progenitor cells (CD34(+) CD19(+)) cell dose is associated with a significant
      decrease incidence of acute GvHD.

PMID- 19183191
TI  - Bortezomib, low-dose intravenous melphalan, and dexamethasone for patients with
      relapsed multiple myeloma.
AB  - This multicenter phase I/II study investigated the maximum tolerated dose (MTD),
      safety, and efficacy of low dose intravenous (IV) melphalan in combination with
      bortezomib for patients with relapsed multiple myeloma (MM). Patients received
      bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 and escalating doses of IV
      melphalan (2.5-10.0 mg/m(2)) on day 2 of a 28-day cycle for a maximum of eight
      cycles. Dexamethasone 20 mg was added for progressive or stable disease. Fifty
      three patients were enrolled. The MTD was defined at melphalan 7.5 mg/m(2) and
      bortezomib 1.3 mg/m(2). The overall response rate (ORR) was 68% (23% complete or
      near-complete responses [CR/nCR]) whilst at the MTD (n = 33) the ORR was 76% (34%
      CR/nCR). After median follow-up of 17 months, the median progression free
      survival was 10 months, rising to 12 months at the MTD (P < 0.05 vs. non-MTD
      regimens). The median overall survival was 28 months, but was not yet reached at
      the MTD. Grade 3/4 adverse events included thrombocytopenia (62%), neutropenia
      (57%), infection (21%), and neuropathy (15%). Bortezomib and low-dose IV
      melphalan combination therapy is a safe and highly effective regimen for patients
      with relapsed MM. These data suggest further investigation of this combination is
      warranted.

PMID- 19183192
TI  - The humanized CD40 antibody SGN-40 demonstrates pre-clinical activity that is
      enhanced by lenalidomide in chronic lymphocytic leukaemia.
AB  - Antibody-based therapies, such as rituximab and alemtuzumab, have contributed
      significantly to the treatment of Chronic Lymphocytic leukaemia (CLL). The CD40
      antigen is expressed predominantly on B-cells and represents a potential target
      for immune-based therapies. SGN-40 is a humanized IgG1 monoclonal antibody
      currently in Phase I/II clinical trials for indolent lymphomas, diffuse large B
      cell lymphomas and Multiple Myeloma. Its biological effect on CLL cells has not
      been studied. The present study demonstrated that SGN-40 mediated modest
      apoptosis in a subset of patients with secondary cross-linking but did not
      mediate complement-dependent cytotoxicity. SGN-40 also mediated antibody
      dependent cellular cytotoxicity (ADCC) predominantly through natural killer (NK)
      cells. Previous studies by our group and others have demonstrated that
      lenalidomide upregulates CD40 expression on primary B CLL cells and activates NK
      cells. We therefore examined for the combinatorial effect of lenalidomide and SGN
      40 and demonstrated that both enhanced direct apoptosis and ADCC against primary
      CLL B cells. These data together provide justification for clinical trials of SGN
      40 and lenalidomide in combination for CLL therapy.

PMID- 19183194
TI  - Rediscovering alemtuzumab: current and emerging therapeutic roles.
AB  - The humanized anti-CD52 monoclonal antibody alemtuzumab belongs to the family of
      Campath-1 antibodies, which were initially developed for their ability to prevent
      graft-versus-host disease (GVHD) and graft rejection in stem cell
      transplantation. Alemtuzumab is indicated for the treatment of chronic
      lymphocytic leukaemia (CLL) and has demonstrated considerable activity in
      relapsed/refractory disease and in previously untreated disease. It has been
      shown to induce minimal residual disease-negative responses as a single agent or
      as part of consolidation therapy in a meaningful proportion of patients with CLL
      and has shown promising activity in patients with high-risk cytogenetic markers.
      Alemtuzumab may also have significant activity in T-cell malignancies, such as
      mycosis fungoides and T-cell prolymphocytic leukaemia. Recent studies also have
      evaluated alemtuzumab as part of a conditioning regimen to prevent GVHD in stem
      cell transplantation. This article reviews our current understanding of
      alemtuzumab and discusses its emerging role in the treatment of CLL and other
      haematological malignancies.

PMID- 19183195
TI  - Involvement of macroautophagy in the caspase-independent killing of Burkitt
      lymphoma cell lines by rituximab.

PMID- 19183193
TI  - Gene expression of anti- and pro-apoptotic proteins in malignant and normal
      plasma cells.
AB  - The survival of malignant plasma cells is a key event in disease occurrence,
      progression and chemoresistance. Using DNA-microarrays, we analysed the
      expression of genes coding for 58 proteins linked with extrinsic and intrinsic
      apoptotic pathways, caspases and inhibitor of apoptosis proteins. We considered
      six memory B cells (MBC), seven plasmablasts (PPC), seven bone marrow plasma
      cells (BMPC) and purified myeloma cells (MMC) from 92 newly-diagnosed patients.
      Forty out of the 58 probe sets enabled the separation of MBC, PPC and BMPC in
      three homogeneous clusters, characterized by an elevated expression of TNFRSF10A,
      TNFRSF10B, BCL2A1, CASP8, CASP9 and PMAIP1 genes for MBC, of FAS, FADD, AIFM1,
      BIRC5, CASP CASP2, CASP3 and CASP6 for PPC and of BCL2, MCL1, BID, BIRC3 and XIAP
      for BMPC. Thus, B cell differentiation was associated with change of expression
      of pro-apoptotic and anti-apoptotic genes. Regarding MMC, the major finding was
      TRAIL upregulation that might be counteracted by a high osteoprotegerin
      production by BM stromal cells and a decreased expression of FAS, APAF1 and BNIP3
      compared to normal BMPC. Out of the 40 genes, CASP2 and BIRC5 expression in MMC
      had adverse prognosis in two independent series of previously-untreated patients.

PMID- 19183196
TI  - Micronodular T-cell/histiocyte-rich B-cell lymphoma in spleen.

PMID- 19183197
TI  - Bone marrow engraftment in pulmonary vessels.

PMID- 19183198
TI  - Serial chimerism analyses indicate that mixed haemopoietic chimerism influences
      the probability of graft rejection and disease recurrence following allogeneic
      stem cell transplantation (SCT) for severe aplastic anaemia (SAA): indication for
      routine assessment of chimerism post SCT for SAA.
AB  - Ninety-one patients were studied serially for chimeric status following
      allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA) or
      Fanconi Anaemia (FA). Short tandem repeat polymerase chain reaction (STR-PCR) was
      used to stratify patients into five groups: (A) complete donor chimeras (n = 39),
      (B) transient mixed chimeras (n = 15) (C) stable mixed chimeras (n = 18), (D)
      progressive mixed chimeras (n = 14) (E) recipient chimeras with early graft
      rejection (n = 5). As serial sampling was not possible in Group E, serial
      chimerism results for 86 patients were available for analysis. The following
      factors were analysed for association with chimeric status: age, sex match, donor
      type, aetiology of aplasia, source of stem cells, number of cells engrafted,
      conditioning regimen, graft-versus-host disease (GvHD) prophylaxis, occurrence of
      acute and chronic GvHD and survival. Progressive mixed chimeras (PMCs) were at
      high risk of late graft rejection (n = 10, P < 0.0001). Seven of these patients
      lost their graft during withdrawal of immunosuppressive therapy. STR-PCR
      indicated an inverse correlation between detection of recipient cells post-SCT
      and occurrence of acute GvHD (P = 0.008). PMC was a bad prognostic indicator of
      survival (P = 0.003). Monitoring of chimeric status during cyclosporin withdrawal
      may facilitate therapeutic intervention to prevent late graft rejection in
      patients transplanted for SAA.

PMID- 19183199
TI  - Thyroid hormone beta receptor activation has additive cholesterol lowering
      activity in combination with atorvastatin in rabbits, dogs and monkeys.
AB  - BACKGROUND AND PURPOSE: Thyroid hormone receptor (TR) agonists are in clinical
      trials for the treatment of hypercholesterolaemia. As statins are the standard of
      clinical care, any new therapies must have adjunctive activity, when given in
      combination with statins. As already known for the statins, the cholesterol
      lowering effect of TR activation involves increased expression of the low-density
      lipoprotein receptor. Using animal models, we tested whether TR activation would
      have additive cholesterol lowering activity in the presence of effective doses of
      a statin. EXPERIMENTAL APPROACH: We evaluated the activity of a liver-targeted
      prodrug, MB07811, of a novel TH receptor beta agonist, MB07344, as monotherapy
      and in combination with atorvastatin in rabbits, dogs and monkeys. KEY RESULTS:
      In rabbits, MB07344 (i.v.) decreased total plasma cholesterol (TPC) comparable to
      that achieved with a maximally effective dose of atorvastatin (p.o.). The
      addition of MB07344 to atorvastatin resulted in a further decrease in TPC.
      Similarly, the addition of MB07811 (p.o.) to atorvastatin treatment decreased TPC
      beyond the level achieved with either agent as monotherapy. In dogs and monkeys,
      atorvastatin and MB07811 were administered as monotherapy or in combination.
      Consistent with the rabbit studies, the combination treatment caused a greater
      decrease in TPC than either MB07811 or atorvastatin administered as monotherapy.
      CONCLUSIONS AND IMPLICATIONS: We conclude that the effects of MB07811 and
      atorvastatin in lowering cholesterol are additive in animals. These results would
      encourage and support the demonstration of similarly improved efficacy of
      combination versus monotherapy with such agents in the clinic.

PMID- 19183200
TI  - Effects of land use on threatened species.
AB  - There is widespread agreement that biodiversity loss must be reduced, yet to
      alleviate threats to plant and animal species, the forces driving these losses
      need to be better understood. We searched for explanatory variables for
      threatened-species data at the country level through land-use information instead
      of previously used socioeconomic and demographic variables. To explain the number
      of threatened species in one country, we used information on land-use patterns in
      all neighboring countries and on the extent of the country's sea border. We
      carried out multiple regressions of the numbers of threatened species as a
      function of land-use patterns, and we tested various specifications of this
      function, including spatial autocorrelation. Most cross-border land-use patterns
      had a significant influence on the number of threatened species, and land-use
      patterns explained the number of threatened species better than less proximate
      socioeconomic variables. More specifically, our overall results showed a highly
      adverse influence of plantations and permanent cropland, a weaker negative
      influence of permanent pasture, and, for the most part, a beneficial influence of
      nonarable lands and natural forest. Surprisingly, built-up land also showed a
      conserving influence on threatened species. The adverse influences extended to
      distances between about 250 km (plants) and 2000 km (birds and mammals) away from
      where the species threat was recorded, depending on the species. Our results
      highlight that legislation affecting biodiversity should look beyond national
      boundaries.

PMID- 19183201
TI  - Advantages of volunteer-based biodiversity monitoring in Europe.
AB  - Without robust and unbiased systems for monitoring, changes in natural systems
      will remain enigmatic for policy makers, leaving them without a clear idea of the
      consequences of any environmental policies they might adopt. Generally,
      biodiversity-monitoring activities are not integrated or evaluated across any
      large geographic region. The EuMon project conducted the first large-scale
      evaluation of monitoring practices in Europe through an on-line questionnaire and
      is reporting on the results of this survey. In September 2007 the EuMon project
      had documented 395 monitoring schemes for species, which represents a total
      annual cost of about 4 million euro, involving more than 46,000 persons devoting
      over 148,000 person-days/year to biodiversity-monitoring activities. Here we
      focused on the analysis of variations of monitoring practices across a set of
      taxonomic groups (birds, amphibians and reptiles, mammals, butterflies, plants,
      and other insects) and across 5 European countries (France, Germany, Hungary,
      Lithuania, and Poland). Our results suggest that the overall sampling effort of a
      scheme is linked with the proportion of volunteers involved in that scheme.
      Because precision is a function of the number of monitored sites and the number
      of sites is maximized by volunteer involvement, our results do not support the
      common belief that volunteer-based schemes are too noisy to be informative. Just
      the opposite, we believe volunteer-based schemes provide relatively reliable
      data, with state-of-the-art survey designs or data-analysis methods, and
      consequently can yield unbiased results. Quality of data collected by volunteers
      is more likely determined by survey design, analytical methodology, and
      communication skills within the schemes rather than by volunteer involvement per
      se.

PMID- 19183202
TI  - Optimal allocation of resources among threatened species: a project
      prioritization protocol.
AB  - Conservation funds are grossly inadequate to address the plight of threatened
      species. Government and conservation organizations faced with the task of
      conserving threatened species desperately need simple strategies for allocating
      limited resources. The academic literature dedicated to systematic priority
      setting usually recommends ranking species on several criteria, including level
      of endangerment and metrics of species value such as evolutionary
      distinctiveness, ecological importance, and social significance. These approaches
      ignore 2 crucial factors: the cost of management and the likelihood that the
      management will succeed. These oversights will result in misallocation of scarce
      conservation resources and possibly unnecessary losses. We devised a project
      prioritization protocol (PPP) to optimize resource allocation among New Zealand's
      threatened-species projects, where costs, benefits (including species values),
      and the likelihood of management success were considered simultaneously. We
      compared the number of species managed and the expected benefits gained with 5
      prioritization criteria: PPP with weightings based on species value; PPP with
      species weighted equally; management costs; species value; and threat status. We
      found that the rational use of cost and success information substantially
      increased the number of species managed, and prioritizing management projects
      according to species value or threat status in isolation was inefficient and
      resulted in fewer species managed. In addition, we found a clear trade-off
      between funding management of a greater number of the most cost-efficient and
      least risky projects and funding fewer projects to manage the species of higher
      value. Specifically, 11 of 32 species projects could be funded if projects were
      weighted by species value compared with 16 projects if projects were not
      weighted. This highlights the value of a transparent decision-making process,
      which enables a careful consideration of trade-offs. The use of PPP can
      substantially improve conservation outcomes for threatened species by increasing
      efficiency and ensuring transparency of management decisions.

PMID- 19183203
TI  - Pyric herbivory: rewilding landscapes through the recoupling of fire and grazing.
AB  - Our understanding of fire and grazing is largely based on small-scale
      experimental studies in which treatments are uniformly applied to experimental
      units that are considered homogenous. Any discussion of an interaction between
      fire and grazing is usually based on a statistical approach that ignores the
      spatial and temporal interactions on complex landscapes. We propose a new focus
      on the ecological interaction of fire and grazing in which each disturbance is
      spatially and temporally dependent on the other and results in a landscape where
      disturbance is best described as a shifting mosaic (a landscape with patches that
      vary with time since disturbance) that is critical to ecological structure and
      function of many ecosystems. We call this spatiotemporal interaction pyric
      herbivory (literal interpretation means grazing driven by fire). Pyric herbivory
      is the spatial and temporal interaction of fire and grazing, where positive and
      negative feedbacks promote a shifting pattern of disturbance across the
      landscape. We present data we collected from the Tallgrass Prairie Preserve in
      the southern Great Plains of North America that demonstrates that the interaction
      between free-roaming bison (Bison bison) and random fires promotes heterogeneity
      and provides the foundation for biological diversity and ecosystem function of
      North American and African grasslands. This study is different from other studies
      of fire and grazing because the fires we examined were random and grazing animals
      were free to roam and select from burned and unburned patches. For ecosystems
      across the globe with a long history of fire and grazing, pyric herbivory with
      any grazing herbivore is likely more effective at restoring evolutionary
      disturbance patterns than a focus on restoring any large vertebrate while
      ignoring the interaction with fire and other disturbances.

PMID- 19183204
TI  - Interactions between ecological traits and host plant type explain distribution
      change in noctuid moths.
AB  - The ecological traits of species determine how well a species can withstand
      threats to which it is exposed. If these predisposing traits can be identified,
      species that are most at risk of decline can be identified and an understanding
      of the processes behind the declines can be gained. We sought to determine how
      body size, specificity of larval host plant, overwintering stage, type of host
      plant, and the interactions of these traits are related to the distribution
      change in noctuid moths. We used data derived from the literature and analyzed
      the effects of traits both separately and simultaneously in the same model. When
      we analyzed the traits separately, it seemed the most important determinants of
      distribution change were overwintering stage and type of host plant.
      Nevertheless, ecological traits are often correlated and the independent effect
      of each trait may not be seen in analyses in which traits are analyzed
      separately. When we accounted for other correlated traits, the results were
      substantially different. Only one trait (body size), but 3 interactions,
      explained distribution change. This finding suggests that distribution change is
      not determined by 1 or 2 traits; rather, the effect of the traits depends on
      other interacting traits. Such complexity makes it difficult to understand the
      processes behind distribution changes and emphasizes the need for basic
      ecological knowledge of species. With such basic knowledge, a more accurate
      picture of the factors causing distribution changes and increasing risk of
      extinction might be attainable.

PMID- 19183205
TI  - Role of crab herbivory in die-off of New England salt marshes.
AB  - Die-offs of cordgrass are pervasive throughout western Atlantic salt marshes, yet
      understanding of the mechanisms precipitating these events is limited. We tested
      whether herbivory by the native crab, Sesarma reticulatum, is generating die-offs
      of cordgrass that are currently occurring on Cape Cod, Massachusetts (U.S.A.), by
      manipulating crab access to cordgrass transplanted into die-off areas and healthy
      vegetation. We surveyed 12 Cape Cod marshes to investigate whether the extent of
      cordgrass die-off on creek banks, where die-offs are concentrated, was related to
      local Sesarma grazing intensity and crab density. We then used archived aerial
      images to examine whether creek bank die-off areas have expanded over the past 2
      decades and tested the hypothesis that release from predation, leading to
      elevated Sesarma densities, is triggering cordgrass die-offs by tethering crabs
      where die-offs are pervasive and where die-offs have not yet been reported.
      Intensity of crab grazing on transplanted cordgrass was an order of magnitude
      higher in die-off areas than in adjacent vegetation. Surveys revealed that
      Sesarma herbivory has denuded nearly half the creek banks in Cape Cod marshes,
      and differences in crab-grazing intensity among marshes explained >80% of
      variation in the extent of the die-offs. Moreover, the rate of die-off expansion
      and area of marsh affected have more than doubled since 2000. Crab-tethering
      experiments suggest that release from predation has triggered elevated crab
      densities that are driving these die-offs, indicating that disruption of predator
      prey interactions may be generating the collapse of marsh ecosystems previously
      thought to be exclusively under bottom-up control.

PMID- 19183206
TI  - Interactive effects of harvest and deer herbivory on the population dynamics of
      American ginseng.
AB  - Few demographic models for any species consider the role of multiple, interacting
      ecological threats. Many forest herbs are heavily browsed by white-tailed deer
      (Odocoileus virginianus) and a number of these are also harvested for the
      medicinal, floral, or horticultural trades. Previous studies of the viability of
      American ginseng (Panax quinquefolius) have separately examined the effects of
      harvesting and deer herbivory. We followed individually marked ginseng plants in
      6 populations for 8 years and documented deer browse levels, conducted helicopter
      surveys to estimate the deer herd size, and documented 2 ginseng harvests. We
      used this long-term data set to develop a stochastic demographic model that
      quantified the separate and interactive role of these threats to ginseng
      viability. Although harvesting and deer herbivory negatively affected ginseng
      population growth, their effects were not additive. Deer herbivory negatively
      affected population growth in the absence but not in the presence of harvesting.
      Life table response experiments revealed that in the presence of harvesting, deer
      herbivory had some positive effects on vital rates because browsed plants were
      less apparent to harvesters. Ginseng populations that were harvested responsibly
      (i.e., planting seeds from harvested individuals) had higher growth rates than
      those that were harvested irresponsibly. We concluded that both deer populations
      and harvesting must be managed to ensure sustainable populations of American
      ginseng. Our findings underscore the importance of long-term monitoring to assess
      threats to viability and the need for a broad ecological understanding of the
      complexity of ecosystem management.

PMID- 19183207
TI  - Crossing invisible boundaries: the effectiveness of the Langebaan Lagoon marine
      protected area as a harvest refuge for a migratory fish species in South Africa.
AB  - The application of no-take areas in fisheries remains controversial. Critics
      argue that many targeted species are too mobile to benefit from area protection
      and that no-take areas are only appropriate for resident species. The degree of
      protection does not depend on the size of the no-take area but rather on the time
      fish reside inside its boundaries during key life-history events (i.e., spawning)
      and during periods of peak fishing activity. We evaluated the potential of a
      small no-take marine protected area (MPA) inside a coastal embayment as a harvest
      refuge for a mobile, possibly migratory, long-lived fish species. We used
      acoustic telemetry to track movements of 30 transmitter-tagged white stumpnose
      (Rhabdosargus globiceps) across and on both sides of the boundary of a small (34
      km(2)) no-take area over a full year. Being landlocked on 3 sides, the location
      of the MPA inside the lagoon made it practical to detect all boundary crossings
      and to calculate the time individual fish used the MPA. We detected frequent
      movements across the boundary, with strong seasonal and individual variations.
      There were significant differences in MPA use patterns between fish from
      different release areas. The time spent in the MPA by individual fish during
      summer (mean 50%; max 98%) was out of proportion with the size of that area (4%
      of total habitat). Summer coincided with peak recreational fishing activity and
      with the spawning season of this species. The small MPA provided a refuge for a
      part of the spawning stock of white stumpnose. Our findings suggest that if
      strategically placed, a small no-take area can be effective in protecting mobile
      species and that models of spillover from no-take areas should account for
      seasonal and individual variation in area use and the spatiotemporal distribution
      of fish and fishers.

PMID- 19183208
TI  - Disturbance-response analysis: a method for rapid assessment of the threat to
      species in disturbed areas.
AB  - We developed a method with which to analyze a specie's response to chronic
      anthropogenic disturbance (CAD). We regressed density of individuals on the
      intensity of 3 disturbance agents (human activities, raising livestock, and land
      degradation) along CAD gradients to determine how much CAD is experienced by a
      species; whether species are ruderal (achieving maximum densities in disturbed
      sites); whether density declines as a result of CAD; which disturbance agents are
      responsible for this reduction; and the number of populations that decline as a
      result of CAD. We tested the method on 9 threatened Mammillaria species
      (Cactaceae). Seven species were ruderal. In 4 species, actual disturbance
      surpassed the CAD intensity in which plants achieved their maximum densities;
      thus, the density of those 4 species appeared to be declining. For 7 species,
      some populations were threatened by human activities or livestock, whereas others
      were favored by them. Land degradation negatively affected all species. Our
      results allowed us to distinguish 4 groups of species that had similar responses
      and thus may require different forms of management. Our method provided an
      estimation of the growth rate (lambda) of the studied populations that was
      significantly correlated with lambdas obtained from demographic studies. The size
      structures of populations were consistent with the predictions of the analysis,
      which suggests our results are consistent and reliable. Disturbance-response
      analysis provides a basis for management in heavily populated areas, where
      conservation must be achieved along with development activities that cause CAD.
      The method provides readily interpretable information, which facilitates
      participative decision making; the data are rapidly generated, which makes it
      appropriate when results are required promptly or for assessment of large numbers
      of species; and it provides a comprehensive perception of how threatened species
      behave in the real world.

PMID- 19183209
TI  - Acceleration of exotic plant invasion in a forested ecosystem by a generalist
      herbivore.
AB  - The successful invasion of exotic plants is often attributed to the absence of
      coevolved enemies in the introduced range (i.e., the enemy release hypothesis).
      Nevertheless, several components of this hypothesis, including the role of
      generalist herbivores, remain relatively unexplored. We used repeated censuses of
      exclosures and paired controls to investigate the role of a generalist herbivore,
      white-tailed deer (Odocoileus virginianus), in the invasion of 3 exotic plant
      species (Microstegium vimineum, Alliaria petiolata, and Berberis thunbergii) in
      eastern hemlock (Tsuga canadensis) forests in New Jersey and Pennsylvania
      (U.S.A.). This work was conducted in 10 eastern hemlock (T. canadensis) forests
      that spanned gradients in deer density and in the severity of canopy disturbance
      caused by an introduced insect pest, the hemlock woolly adelgid (Adelges tsugae).
      We used maximum likelihood estimation and information theoretics to quantify the
      strength of evidence for alternative models of the influence of deer density and
      its interaction with the severity of canopy disturbance on exotic plant
      abundance. Our results were consistent with the enemy release hypothesis in that
      exotic plants gained a competitive advantage in the presence of generalist
      herbivores in the introduced range. The abundance of all 3 exotic plants
      increased significantly more in the control plots than in the paired exclosures.
      For all species, the inclusion of canopy disturbance parameters resulted in
      models with substantially greater support than the deer density only models. Our
      results suggest that white-tailed deer herbivory can accelerate the invasion of
      exotic plants and that canopy disturbance can interact with herbivory to magnify
      the impact. In addition, our results provide compelling evidence of nonlinear
      relationships between deer density and the impact of herbivory on exotic species
      abundance. These findings highlight the important role of herbivore density in
      determining impacts on plant abundance and provide evidence of the operation of
      multiple mechanisms in exotic plant invasion.

PMID- 19183210
TI  - Patch-occupancy modeling as a method for monitoring changes in forest floristics:
      a case study in southeastern Australia.
AB  - The ability to monitor changes in biodiversity is fundamental to demonstrating
      sustainable management practices of natural resources. Disturbance studies
      generally focus on responses at the plot scale, whereas landscape-scale responses
      are directly relevant to the development of sustainable forest management.
      Modeling changes in occupancy is one way to monitor landscape-scale responses. We
      used understory vegetation data collected over 16 years from a long-term study
      site in southeastern Australia. The site was subject to timber harvesting and
      frequent prescribed burning. We used occupancy models to examine the impacts of
      these disturbances on the distribution of 50 species of plants during the study.
      Timber harvesting influenced the distribution of 9 species, but these effects of
      harvesting were generally lost within 14 years. Repeated prescribed fire affected
      22 species, but the heterogeneity of the burns reduced the predicted negative
      effects. Twenty-two species decreased over time independent of treatment, and
      only 5 species increased over time. These changes probably represent a natural
      response to a wildfire that occurred in 1973, 13 years before the study began.
      Occupancy modeling is a useful and flexible technique for analyzing monitoring
      data and it may also be suitable for inclusion within an adaptive-management
      framework for forest management.

PMID- 19183211
TI  - Evaluation of local ecological knowledge as a method for collecting extensive
      data on animal abundance.
AB  - The use of local ecological knowledge (LEK) has been advocated for biodiversity
      monitoring and management. To date, however, it has been underused in studying
      wild populations of animals and, particularly, in obtaining quantitative
      abundance estimates. We evaluated LEK as a tool for collecting extensive data on
      local animal abundance and population trends. We interviewed shepherds in
      southeastern Spain, asking them to estimate the local abundance of the
      terrestrial tortoise Testudo graeca. We quantified reliability of abundance
      estimates derived from interviews by comparing them with those obtained from
      standard field-sampling protocols (distance sampling). We also explored the
      complementarity of these 2 approaches. LEK provided high-quality and low-cost
      information about both distribution and abundance of T. graeca. Interviews with
      shepherds yielded abundance estimates in a much wider range than linear
      transects, which only detected the species in the upper two-thirds of its
      abundance range. Abundance estimates from both methodologies showed a close
      relationship. Analysis of confidence intervals indicated local knowledge could be
      used to estimate mean local abundances and to detect mean population trends. A
      cost analysis determined that the information derived from LEK was 100 times
      cheaper than that obtained through linear-transect surveys. Our results should
      further the use of LEK as a standard tool for sampling the quantitative abundance
      of a great variety of taxa, particularly when population densities are low and
      traditional sampling methods are expensive or difficult to implement.

PMID- 19183212
TI  - Role of genetic refuges in the restoration of native gene pools of brown trout.
AB  - Captive-bred animals derived from native, alien, or hybrid stocks are often
      released in large numbers in natural settings with the intention of augmenting
      harvests. In brown trout (Salmo trutta), stocking with hatchery-reared non-native
      fish has been the main management strategy used to maintain or improve depleted
      wild brown trout populations in Iberian and other Mediterranean regions. This
      measure has become a serious threat to the conservation of native genetic
      diversity, mainly due to introgressive hybridization. Aware of this risk, the
      agency responsible for management of brown trout in the eastern Pyrenees (Spain)
      created "brown trout genetic refuges" to preserve the integrity of brown trout
      gene pools in this region. Within refuge areas, the prerefuge status with respect
      to fishing activities has been maintained, but hatchery releases have been banned
      completely. We evaluated this management strategy through a comparison of the
      stocking impact on native populations that accounted for stocking histories
      before and after refuge designations and fishing activities. In particular we
      examined the relevant scientific, cultural, and political challenges encountered.
      Despite agency willingness to change fishery policies to balance exploitation and
      conservation, acceptance of these new policies by anglers and genetic monitoring
      of refuge populations should also be considered. To improve management supported
      by genetic refuges, we suggest focusing on areas where the public is more
      receptive, considering the situation of local native diversity, and monitoring of
      adjacent introgressed populations. We recommend the use of directional supportive
      breeding only when a population really needs to be enhanced. In any case,
      management strategies should be developed to allow for protection within the
      context of human use.

PMID- 19183213
TI  - Fish responses to experimental fragmentation of seagrass habitat.
AB  - Understanding the consequences of habitat fragmentation has come mostly from
      comparisons of patchy and continuous habitats. Because fragmentation is a
      process, it is most accurately studied by actively fragmenting large patches into
      multiple smaller patches. We fragmented artificial seagrass habitats and
      evaluated the impacts of fragmentation on fish abundance and species richness
      over time (1 day, 1 week, 1 month). Fish assemblages were compared among 4
      treatments: control (single, continuous 9-m(2) patches); fragmented (single,
      continuous 9-m(2) patches fragmented to 4 discrete 1-m(2) patches);
      prefragmented/patchy (4 discrete 1-m(2) patches with the same arrangement as
      fragmented); and disturbance control (fragmented then immediately restored to
      continuous 9-m(2) patches). Patchy seagrass had lower species richness than
      actively fragmented seagrass (up to 39% fewer species after 1 week), but species
      richness in fragmented treatments was similar to controls. Total fish abundance
      did not vary among treatments and therefore was unaffected by fragmentation,
      patchiness, or disturbance caused during fragmentation. Patterns in species
      richness and abundance were consistent 1 day, 1 week, and 1 month after
      fragmentation. The expected decrease in fish abundance from reduced total
      seagrass area in fragmented and patchy seagrass appeared to be offset by greater
      fish density per unit area of seagrass. If fish prefer to live at edges, then the
      effects of seagrass habitat loss on fish abundance may have been offset by the
      increase (25%) in seagrass perimeter in fragmented and patchy treatments.
      Possibly there is some threshold of seagrass patch connectivity below which fish
      abundances cannot be maintained. The immediate responses of fish to experimental
      habitat fragmentation provided insights beyond those possible from comparisons of
      continuous and historically patchy habitat.

PMID- 19183214
TI  - Documenting loss of large trophy fish from the Florida Keys with historical
      photographs.
AB  - A loss of large vertebrates has occurred in aquatic and terrestrial ecosystems,
      but data to measure long-term population changes are sparse. Historical
      photographs provide visual and quantitative evidence of changes in mean
      individual size and species composition for groups of marine fish that have been
      targeted by sport fishing. I measured such trends for 13 groups of recreationally
      caught "trophy" reef fish with photographs taken in Key West, Florida, from 1956
      to 2007. The mean fish size declined from an estimated 19.9 kg (SE 1.5) to 2.3 kg
      (SE 0.3), and there was a major shift in species composition. Landings from 1956
      to 1960 were dominated by large groupers (Epinephelus spp.), and other large
      predatory fish were commonly caught, including sharks with an average length of
      just <2 m. In contrast, landings in 2007 were composed of small snappers
      (Lutjanus spp. and Ocyurus chrysurus) with an average length of 34.4 cm (SE
      0.62), and the average length of sharks declined by more than 50% over 50 years.
      Major declines in the size of fish caught were not reflected in the price of
      fishing trips, so customers paid the same amount for a less-valuable product.
      Historical photographs provide a window into a more pristine coral reef ecosystem
      that existed a half a century ago and lend support to current observations that
      unfished reef communities are able to support large numbers of large-bodied fish.

PMID- 19183215
TI  - Leadership: a new frontier in conservation science.
AB  - Leadership is a critical tool for expanding the influence of conservation
      science, but recent advances in leadership concepts and practice remain
      underutilized by conservation scientists. Furthermore, an explicit conceptual
      foundation and definition of leadership in conservation science are not available
      in the literature. Here we drew on our diverse leadership experiences, our
      reading of leadership literature, and discussions with selected conservation
      science leaders to define conservation-science leadership, summarize an
      exploratory set of leadership principles that are applicable to conservation
      science, and recommend actions to expand leadership capacity among conservation
      scientists and practitioners. We define 2 types of conservation-science
      leadership: shaping conservation science through path-breaking research, and
      advancing the integration of conservation science into policy, management, and
      society at large. We focused on the second, integrative type of leadership
      because we believe it presents the greatest opportunity for improving
      conservation effectiveness. We identified 8 leadership principles derived mainly
      from the "adaptive leadership" literature: recognize the social dimension of the
      problem; cycle frequently through action and reflection; get and maintain
      attention; combine strengths of multiple leaders; extend your reach through
      networks of relationships; strategically time your effort; nurture productive
      conflict; and cultivate diversity. Conservation scientists and practitioners
      should strive to develop themselves as leaders, and the Society for Conservation
      Biology, conservation organizations, and academia should support this effort
      through professional development, mentoring, teaching, and research.

PMID- 19183217
TI  - Haploinsufficiency of the nerve growth factor beta gene in a 1p13 deleted female
      child with an insensitivity to pain.
AB  - Pain insensitivity is mediated at the genetic level by the disruption of specific
      genes associated with neuronal development. Mammalian in vivo and in vitro
      studies have shown the nerve growth factor (NGF) gene to play an integral role in
      nerve maintenance and function. Pain insensitivity in humans can be attributed to
      hereditary sensory and autonomic neuropathies (HSAN) of which there are five
      classes (HSAN I - HSAN V). The human nerve growth factor beta gene (NGFB) located
      on chromosome 1p13.2 has been found to cause HSAN V within individuals homozygous
      for a point mutation in NGFB. Although heterozygotes can display a milder
      phenotype, this has only been observed in adults. We report a karyotypically
      normal 5-year-old female with developmental delay, mild facial dysmorphism, and
      unsteady gait. Pain and thermal insensitivity were noted as were recurrent mouth
      ulcers, facial flushing, recurrent episodes of increased body temperature and
      unexplained sweating, indicative of a sensory neuropathy with mild autonomic
      involvement. Array comparative genomic hybridization (aCGH) analysis revealed a
      de-novo deletion within chromosome 1p13 of the child involving the NGFB gene.
      Sequence analysis of the homologous NGFB gene identified no mutation, implying
      that sensory neuropathy was caused by haploinsufficiency of the NGFB gene.

PMID- 19183216
TI  - Coprophenomena in Tourette syndrome.
AB  - The aims of this descriptive study were to examine the prevalence and
      associations of coprophenomena (involuntary expression of socially unacceptable
      words or gestures) in individuals with Tourette syndrome. Participant data were
      obtained from the Tourette Syndrome International Database Consortium. A
      specialized data collection form was completed for each of a subset of 597
      consecutive new patients with Tourette syndrome from 15 sites in seven countries.
      Coprolalia occurred at some point in the lifetime of 19.3% of males and 14.6% of
      females, and copropraxia in 5.9% of males and 4.9% of females. Coprolalia was
      three times as frequent as copropraxia, with a mean onset of each at about 11
      years, 5 years after the onset of tics. In 11% of those with coprolalia and 12%
      of those with copropraxia these coprophenomena were one of the initial symptoms
      of Tourette syndrome. The onsets of tics, coprophenomena, smelling of non-food
      objects, and spitting were strongly intercorrelated. Early onset of
      coprophenomena was not associated with its longer persistence. The most robust
      associations of coprophenomena were with the number of non-tic repetitive
      behaviors, spitting, and inappropriate sexual behavior. Although coprophenomena
      are a frequently feared possibility in the course of Tourette syndrome, their
      emergence occurs in only about one in five referred patients. Because the course
      and actual impact of coprophenomena are variable, additional prospective research
      is needed to provide better counseling and prognostic information.

PMID- 19183218
TI  - Functional brain mapping of ictal activity in gelastic epilepsy associated with
      hypothalamic hamartoma: a case report.
AB  - Hypothalamic hamartomas (HHs) have been demonstrated as the cause of gelastic
      epilepsy, both by intracranial electrodes and functional imaging. The neocortex
      becomes secondarily involved, through poorly characterized propagation pathways.
      The detailed dynamics of seizure spread have not yet been demonstrated, owing to
      the limited spatial-temporal resolution of available functional mapping. We
      studied a patient with epilepsy associated with HH and gelastic epilepsy.
      Simultaneous electroencephalography (EEG) and functional magnetic resonance
      imaging (fMRI) of several seizure events were obtained, with blood oxygen level
      dependent (BOLD) activation of the hamartoma, and left hemisphere hypothalamus,
      hippocampus, parietal-occipital area, cingulate gyrus, and dorsal-lateral frontal
      area. Integration of regional BOLD kinetics and EEG power dynamics strongly
      suggests propagation of the epileptic activity from the HH through the left
      fornix to the temporal lobe, and later through the cingulate fasciculus to the
      left frontal lobe. The EEG/fMRI method has the spatial-temporal resolution to
      study the dynamics of seizure activity, with detailed demonstration of origin and
      propagation pathways.

PMID- 19183219
TI  - The association between depression and epilepsy in a nationally representative
      sample.
AB  - PURPOSE: To determine the: (1) national prevalence of epilepsy and depression;
      (2) prevalence of depression among those with epilepsy; (3) odds ratio of
      depression among those with epilepsy compared to those without, controlling for
      demographic characteristics; (4) demographic correlates of depression among those
      with epilepsy and those without; and, (5) health services utilization of those
      with epilepsy and depression. METHODS: The full sample of the nationally
      representative 2000/2001 Canadian Community Health Survey (n = 130,880) was used
      to determine prevalence of epilepsy and depression. A subsample of 781
      individuals reporting an epilepsy diagnosis and with complete depression data was
      used to determine prevalence and correlates of depression, and health service
      utilization patterns. Correlates of depression among those without epilepsy (n =
      126,104) were also determined. Chi-square analyses, t-tests, prevalence ratios,
      and a logistic regression were conducted. RESULTS: Thirteen percent of those with
      epilepsy were depressed, in comparison to 7% of those without (p < 0.001).
      Epilepsy was associated with 43% higher odds of depression when adjusting for
      demographic factors. The odds of depression among individuals with epilepsy were
      higher for females, visible minorities, older individuals, and individuals
      experiencing food insecurity. Visible minority and older age appear to be unique
      risk factors for depression in those with epilepsy as compared to those without.
      Thirty-eight percent of depressed respondents with epilepsy had no consultations
      with a mental health professional in the previous year. DISCUSSION: Medical
      professionals need to regularly assess levels of depression in their patients
      with epilepsy. This research helps guide which risk groups should be targeted.

PMID- 19183220
TI  - Morphine dependence increases the response to a brief pentylenetetrazol
      administration in rat hippocampal CA1 in vitro.
AB  - PURPOSE: Herein we used electrophysiologic approaches in hippocampal area CA1 to
      estimate how morphine treatment alters the pentylenetetrazol (PTZ) effects.
      METHODS: Hippocampal slices taken from either control animals or animals made
      dependent via chronic morphine administration were examined. Changes in the
      population spike and epileptiform amplitudes were used as indices to quantify the
      effects of PTZ exposure in the control and morphine-dependent slices. Hippocampal
      slices taken either from control animals or from animals made dependent upon
      morphine were exposed to PTZ, either with or without morphine, naloxone, or
      morphine + naloxone. RESULTS: Morphine dependence increased a PTZ-induced long
      term potentiation (LTP) of the population spike in CA1 in vitro. This LTP was not
      found in rats that had spontaneously withdrawn morphine or withdrawn with
      naloxone in vivo after chronic morphine intake. Morphine or naloxone in vitro
      blocked the PTZ-induced LTP changes in control and morphine-dependent slices.
      However, PTZ-induced multiple population spikes (epileptiform activity) in CA1
      was not blocked by naloxone. DISCUSSION: It is concluded that dependence on
      morphine enhances PTZ-induced plastic and epileptic changes in CA1 excitability.
      We suggest that this model of neuronal activity in dependent slices could present
      an opportunity for studying the mechanisms underlying the increased likelihood of
      seizures in morphine users.

PMID- 19183221
TI  - Valproate-induced metabolic changes in patients with epilepsy: assessment with H
      MRS.
AB  - PURPOSE: Valproate (VPA) interferes with mitochondrial metabolism causing
      hyperammonemia, thereby shifting the balance reaction of glutamine
      (Gln)/glutamate (Glu) toward Gln. In this study we wanted to determine whether
      metabolic changes could be reproduced in VPA-treated patients with epilepsy and
      whether the results differed from those known in chronic hepatic encephalopathy
      (CHE). METHODS: Seven patients with epilepsy pretreated with VPA and seven
      healthy volunteers were investigated on a 3T-scanner. We performed proton
      magnetic resonance spectroscopy ((1)H-MRS) using a short echo time point-resolved
      spectroscopy (PRESS) in the parietal and occipital lobe, respectively. Spectral
      analysis was performed by LCModel, allowing a separation of Glu and Gln at 3T.
      Absolute values of myo-Inositol (mI), choline (Cho), creatine (Cr), N-acetyl
      aspartate (NAA), glutamine (Gln), glutamate (Glu), and the sum of Gln and Glu
      (Glx) were calculated. RESULTS: In the parietal lobe, mI was significantly
      decreased in the patients' group compared to the healthy volunteers. After
      separation of the signals of Gln and Glu, a significant increase of Gln was
      observed in the parietal lobe in the patients' group. No significant differences
      in the occipital spectra could be observed between the groups. DISCUSSION: In VPA
      treated patients the alteration of the Glu/Gln ratio differs from that in
      patients with CHE, where Glx is markedly increased because of an increase in Gln.
      The expected shift from the biochemical balance reaction of Gln/Glu induced by
      VPA could be reproduced for the parietal lobe. Significantly reduced mI in the
      parietal lobe of VPA-treated patients most likely reflects an osmolytic
      compensation for high Gln.

PMID- 19183222
TI  - Focal lesions in the splenium of the corpus callosum in patients with epilepsy.
AB  - PURPOSE: A focal lesion in the splenium of the corpus callosum is a rare finding
      in patients with epilepsy. Intoxication with antiepileptic drugs, edema after
      generalized seizures, or a rapid change of antiepileptic drug levels have been
      proposed as possible mechanisms. The aim of the present study was to analyze the
      relationship between this lesion and possible etiologic factors. PATIENTS AND
      METHODS: We analyzed the magnetic resonance imaging (MRI) scans of 1,050 patients
      undergoing prolonged video-EEG (electroencephalography) monitoring and identified
      24 patients with a focal lesion in the splenium of the corpus callosum. Twenty
      four age- and gender-matched temporal lobe epilepsy patients without such a
      lesion served as a control group. We evaluated the following parameters for their
      possible etiologic significance: epilepsy syndrome, seizure types in medical
      history, seizure frequency during the past year prior to admission for prolonged
      video-EEG monitoring, localization of interictal spikes and ictal EEG patterns in
      patients with focal epilepsies as documented during prolonged video-EEG
      monitoring, seizure types and seizure frequency during prolonged video-EEG
      monitoring, past as well as current antiepileptic medication, withdrawal of
      antiepileptic drugs during monitoring including duration of medication
      withdrawal, and finally drug levels above the therapeutic range. RESULTS: The
      parameters analyzed showed no significant difference between the group of
      patients with focal lesions in the splenium of the corpus callosum and the
      control group. CONCLUSION: We could not identify a single etiologic factor
      responsible for the lesion in the splenium of the corpus callosum.

PMID- 19183223
TI  - Outcome after hemispherectomy in hemiplegic adult patients with refractory
      epilepsy associated with early middle cerebral artery infarcts.
AB  - PURPOSE: To study the outcome after hemispherectomy (HP) in a homogeneous adult
      patient population with refractory hemispheric epilepsy. METHODS: Fourteen adult
      patients submitted to HP were studied. Patients had to be at least 18 years old,
      and have refractory epilepsy, clearly focal lateralized seizures and unilateral
      porencephalus consistent with early middle cerebral artery infarct on magnetic
      resonance imaging (MRI). All patients were submitted to functional
      hemispherectomy. We analyzed age of seizure onset, age by the time of surgery,
      gender, seizure type and frequency, interictal and ictal electroencephalography
      (EEG) findings, MRI and IQ scores preoperatively; seizure frequency, drug
      regimen, and IQ outcome were studied postoperatively. RESULTS: Mean follow-up was
      64 months. All patients had frequent daily seizures preoperatively. All patients
      had unilateral simple partial motor seizures (SPS); 11 patients had secondarily
      generalized tonic-clonic (GTC) seizures and five patients had complex partial
      seizures (CPS), preoperatively. All patients had hemiplegia and hemianopsia.
      Twelve patients had unilateral EEG findings, and in two epileptic discharges were
      seen exclusively over the apparently normal hemisphere. Twelve patients were
      seizure-free after surgery and two patients had at least 90% improvement in
      seizure frequency. Pre- and postoperative mean general IQ was 84 and 88,
      respectively. Five of the twelve Engel I patients were receiving no drugs at last
      follow-up. There was no mortality or major morbidity. CONCLUSIONS: Our results
      suggest that well-selected adult patients might also get good results after HP.
      Although good results were obtained in our adult series, the same procedure
      yielded a much more striking result if performed earlier in life.

PMID- 19183224
TI  - Impact of nonadherence to antiepileptic drugs on health care utilization and
      costs: findings from the RANSOM study.
AB  - PURPOSE: To study the impact of nonadherence to antiepileptic drugs (AEDs) on
      health care utilization and direct medical costs in a Medicaid population.
      METHODS: A retrospective cohort design was employed using state Medicaid claims
      data from Florida, Iowa, and New Jersey during the period from January 1997 to
      June 2006. Patients aged >or=18 years with one or more neurologist visit with an
      epilepsy diagnosis and two or more pharmacy claims for AEDs were included.
      Medication possession ratio (MPR) was used to evaluate AED adherence with MPR
      >or= 0.80 considered adherent and <0.80 considered nonadherent. The association
      of nonadherence with utilization outcomes [hospitalizations, inpatient days,
      emergency department (ED), and outpatient visits] was assessed with univariate
      and multivariate Poisson regressions. Quarterly per-patient inpatient,
      outpatient, ED, and pharmacy costs were calculated across nonadherent and
      adherent quarters for the younger than 65 population (under-65) and cost
      differences were computed. Adjusted incremental costs of nonadherence were
      estimated with multivariate Tobit regression models. RESULTS: A total of 33,658
      patients were included (28,470 under-65), together contributing 388,564 treated
      quarters (26% nonadherent). In multivariate analyses, AED nonadherence was
      associated with significantly higher incidence of hospitalizations [incident rate
      ratio (IRR) = 1.39, 95% confidence interval (CI) = 1.37-1.41], inpatient days
      (IRR = 1.76, 95% CI = 1.75-1.78), and ED visits (IRR = 1.19, 95% CI = 1.18-1.21).
      Nonadherence was associated with cost increases related to serious outcomes,
      including inpatient ($4,320 additional cost per quarter, 95% CI = $4,077-$4,564)
      and ED services ($303 additional cost per quarter, 95% CI = $273-$334), but lower
      costs for outpatient and pharmacy services, likely because of nonadherent
      behavior. DISCUSSION: Nonadherence to AEDs appears to be associated with serious
      outcomes, as evidenced by increased utilization and costs of inpatient and ED
      services.

PMID- 19183225
TI  - Elevated CK-MB mass and plasma brain-type natriuretic peptide concentrations
      following convulsive seizures in children and adolescents: possible evidence of
      subtle cardiac dysfunction.
AB  - PURPOSE: To evaluate the presence of myocardial injury during convulsive seizures
      in children and adolescents by determining serum concentrations of cardiac
      troponin I (cTnI), creatine kinase-MB mass (CK-MB mass), and plasma brain-type
      natriuretic peptide (BNP). METHODS: Thirty-one children (20 boys; mean age, 6.6
      +/- 5.34 years) with convulsive seizures and 50 healthy children were enrolled.
      Serum cTnI, CK-MB mass, and plasma BNP concentrations were analyzed 12 h after
      the seizure and repeated 7 days thereafter in the patient group and obtained one
      time in the control group. RESULTS: The difference between serum concentrations
      of cTnI obtained 12 h and 7 days after the seizure was not statistically
      significant. cTnI levels 12 h postictal and those in control subjects also were
      not significantly different. CK-MB mass and BNP at the 12th h were higher than
      those obtained on the 7th day (p < 0.05 and p < 0.001, respectively). Children
      with seizures had increased levels of CK-MB mass and BNP 12 h after seizure than
      control subjects (p < 0.05 and p < 0.001, respectively). The results of
      electrocardiography (ECG) recordings, which were obtained up to 30 min after
      seizure activity, were completely normal in patients with seizure. CONCLUSION:
      Normal cTnI levels are not indicative of overt myocardial necrosis in patients
      with seizures. However, markedly elevated BNP concentrations together with
      elevated CK-MB mass levels do suggest subtle cardiac dysfunction in patients with
      seizure, and further large-scale studies are warranted.

PMID- 19183226
TI  - Thalamofrontal circuitry and executive dysfunction in recent-onset juvenile
      myoclonic epilepsy.
AB  - PURPOSE: Thalamofrontal abnormalities have been identified in chronic primary
      generalized epilepsy, specifically in juvenile myoclonic epilepsy (JME). These
      regions also underlie executive functioning, although their relationship has yet
      to be examined in JME. This study examined the relationship between thalamic and
      frontal volumes and executive function in recent-onset JME compared to healthy
      control subjects and recent-onset benign childhood epilepsy with centrotemporal
      spikes (BCECTS), a syndrome not typically associated with thalamocortical or
      executive dysfunction. METHODS: Twenty children with recent-onset JME were
      compared to 51 healthy controls and 12 children with BCECTS using quantitative
      magnetic resonance imaging (MRI) and measures of executive abilities.
      Quantitative thalamic and frontal volumes were obtained through semi-automated
      software. Subtests from the Delis-Kaplan Executive Function System (D-KEFS) and
      the Behavior Rating Inventory of Executive Function (BRIEF) were used to measure
      executive function. RESULTS: Executive functions were impaired in JME subjects
      compared to control and BCECTS subjects. Subjects with JME had significantly
      smaller thalamic volumes and more frontal cerebrospinal fluid (CSF) than control
      and BCECTS subjects. Thalamic and frontal volumes were significantly related to
      executive functioning in the JME group, but not in the other two groups.
      DISCUSSION: Children with JME have significant executive dysfunction associated
      with significantly smaller thalami and more frontal CSF. Children with recent
      onset BCECTS do not display the same pattern. Frontal and thalamic volumes appear
      to mediate the relationship between executive functioning and brain structure in
      JME.

PMID- 19183227
TI  - Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results
      from a randomized controlled trial.
AB  - PURPOSE: To evaluate the efficacy and safety of lacosamide (200 and 400 mg/day)
      when added to one to three concomitant antiepileptic drugs (AEDs) in patients
      with uncontrolled partial-onset seizures. METHODS: This multicenter, double
      blind, placebo-controlled trial randomized patients (age 16-70 years) with
      partial-onset seizures with or without secondary generalization to placebo,
      lacosamide 200, or lacosamide 400 mg/day. The trial consisted of an 8-week
      baseline, a 4-week titration, and a 12-week maintenance period. RESULTS: Four
      hundred eighty-five patients were randomized and received trial medication. Among
      these, 87% were taking two or more concomitant AEDs. Median percent reduction in
      seizure frequency per 28 days from baseline to maintenance period (intent-to
      treat, ITT) was 20.5% for placebo, 35.3% for lacosamide 200 mg/day (p = 0.02),
      and 36.4% for 400 mg/day (p = 0.03). In the per protocol population, the
      reductions were 35.3% for lacosamide 200 mg/day (p = 0.04) and 44.9% for 400
      mg/day (p = 0.01) compared to placebo (25.4%). The 50% responder rate for
      lacosamide 400 mg/day (40.5%) was significant (p = 0.01) over placebo (25.8%),
      but was not for 200 mg/day (35.0%). In the per protocol population, the 50%
      responder rate for lacosamide 400 mg/day (46.3%) was significant (p < 0.01)
      compared with the placebo responder rate (27.5%). Dose-related adverse events
      (AEs) included dizziness, nausea, and vomiting. Clinically relevant changes in
      the mean plasma concentrations of commonly used AEDs were not observed.
      DISCUSSION: Results of this trial demonstrated the efficacy and tolerability of
      adjunctive lacosamide 200 and 400 mg/day and support that lacosamide may be an
      advantageous option for the treatment of partial-onset seizures in patients with
      epilepsy.

PMID- 19183228
TI  - Nuclear receptors in the mosquito Aedes aegypti: annotation, hormonal regulation
      and expression profiling.
AB  - In anautogenous mosquitoes, egg development requires blood feeding and as a
      consequence mosquitoes act as vectors of numerous devastating diseases of humans
      and domestic animals. Understanding the molecular mechanisms regulating mosquito
      egg development may contribute significantly to the development of novel vector
      control strategies. Previous studies have shown that in the yellow fever mosquito
      Aedes aegypti, nuclear receptors (NRs) play a key role in the endocrine
      regulation of reproduction. However, many mosquito NRs remain uncharacterized,
      some of which may play an important role in mosquito reproduction. Publication of
      the genome of A. aegypti allowed us to identify all NRs in this mosquito based on
      their phylogenetic relatedness to those within Insecta. We have determined that
      there are 20 putative A. aegypti NRs, some of which are predicted to have
      different isoforms. As the first step toward analysis of this gene family, we
      have established their expression within the two main reproductive tissues of
      adult female mosquitoes: fat body and ovary. All NR transcripts are present in
      both tissues, most displaying dynamic expression profiles during reproductive
      cycles. Finally, in vitro assays with isolated fat bodies were conducted to
      identify the role of the steroid hormone 20-hydroxyecdysone in modulating the
      expression of A. aegypti NRs. These data which describe the identification,
      expression and hormonal regulation of 20 NRs in the yellow fever mosquito lay a
      solid foundation for future studies on the hormonal regulation of reproduction in
      mosquitoes.

PMID- 19183229
TI  - Laparoscopic pyelolithotomy: is the retroperitoneal route a better approach?
AB  - OBJECTIVES: To compare the outcome of laparoscopic pyelolithotomy (LP) using the
      transperitoneal and the retroperitoneal routes. METHODS: Demographics,
      intraoperative and postoperative clinical parameters were evaluated in 48
      laparoscopic pyelolithotomies performed in patients with renal pelvic calculi of
      diameter >30 mm. The differences between the transperitoneal and retroperitoneal
      routes were analyzed. RESULTS: Twenty-seven LP were performed using the
      transperitoneal approach (TLP), and 21 using the retroperitoneal approach (RLP).
      Apart from weight, the patients' demographics and stone size were similar in the
      two groups. Between the RLP and the TLP routes, the operative time was 112.1
      versus 93.2 min (P = 0.01), mean time for oral intake was 1.9 versus 1.2 days (P
      < 0.01), and mean hospital stay was 5.2 versus 3.8 days (P < 0.01). The mean
      postoperative analgesic requirement (2.4 vs 2.2 days, P = 0.41), mean
      convalescence days (9.7 vs 10 days, P = 0.56), and mean estimated blood loss
      (57.2 vs 62.9 ml, P = 0.5) were similar between RPL and TPL respectively. The
      stone-free rate at 3 months follow-up was comparable (88.9% vs 90.5%, P = 0.86).
      The postoperative complications were not significantly different. CONCLUSIONS:
      Compared with the TLP approach, RLP for large renal pelvic stone resulted in a
      shorter operative time, a shorter resumption time for normal oral intake, and a
      shorter hospital stay. As the other clinical outcomes are similar, including the
      stone-free rate, we recommend the RLP route for LP.

PMID- 19183230
TI  - Implications of insulin-like growth factor-I for prostate cancer therapies.
AB  - In the last decade, abundant evidence has suggested that the insulin-like growth
      factor (IGF) family comprises a multi-component network of molecules involved in
      the regulation of both physiological and pathological growth processes in the
      prostate. The IGF axis plays an important role in the tumorigenesis and
      neoplastic growth of prostate cancer. Epidemiological observations indicate that
      circulating IGF-I levels are positively associated with increased risk of
      prostate cancer. Activation of IGF-I receptor (IGF-IR) by IGF-I has mitogenic and
      anti-apoptotic effects on normal and malignant prostate cells. Therapeutic
      alternatives in men with progressive prostate cancer after androgen ablation are
      very limited and more effective therapies are needed for such patients.
      Inactivation of the IGF-I axis represents a potential target to treat androgen
      independent prostate cancer. This review addresses epidemiological studies of IGF
      I and therapeutic strategies including reduction of IGF-I levels, inhibition of
      IGF-IR and the signaling mechanisms involved.

PMID- 19183231
TI  - Effects of insulin replacement on ejaculatory dysfunction in streptozotocin
      induced diabetic rats.
AB  - OBJECTIVES: To investigate the effects of insulin replacement on ejaculatory
      dysfunction in streptozotocin (STZ)-induced diabetic rats. METHODS: Rats were
      divided into three groups: (i) STZ-treated group; (ii) STZ-treated + insulin
      replacement (5 and 2 international units [IU]) group; and (iii) control group.
      The ejaculatory function in rats was evaluated using the spontaneous seminal
      emission (SSE) test. The amount of seminal vesicle fluid (SVF) stored in seminal
      vesicle was measured after the SSE test. Blood glucose was measured using a
      simplified blood glucose meter. RESULTS: In the SSE test, the ejaculatory
      capacity in STZ-induced diabetic rats deteriorated with time after the onset of
      diabetes, and the incidence of SSE and the amount of ejaculated seminal material
      (SM) were significantly decreased from 5 weeks after STZ administration.
      Likewise, the amount of SVF was also significantly decreased in a time-dependent
      manner. One week after STZ administration when ejaculatory capacity had not yet
      diminished, insulin replacement (for 4 weeks) completely prevented the decrease
      in frequency of SSE, the amount of SM and SVF. However, insulin replacement after
      the dysfunction had occurred (5 or 15 weeks after STZ administration) did not
      allow all parameters for ejaculatory function to be restored to the levels of the
      control group. CONCLUSION: This study demonstrates that at an early stage
      following the onset of diabetes, insulin replacement can prevent ejaculatory
      dysfunction in STZ-induced diabetic rats, but once the dysfunction occurs,
      treatment with insulin alone does not restore the ejaculatory capacity to normal
      levels. In addition, this study suggests that the loss of seminal emission that
      results from a decrease in SVF may be involved in the mechanism of ejaculatory
      dysfunction in diabetic rats.

PMID- 19183232
TI  - Effect of reactive oxygen species in semen on the pregnancy of infertile couples.
AB  - OBJECTIVE: We intended retrospectively to investigate whether reactive oxygen
      species (ROS) levels, detected in whole semen, were correlated with the actual
      pregnancy rate. METHODS: A total of 89 patients with data of ROS in semen,
      attending our male infertility clinics from April 1994 to June 2000, were
      evaluated. Semen parameters were determined with computer assisted semen analyzer
      (CASA) and ROS production levels were measured using a computer-driven LKB Wallac
      1251 Luminometer after the addition of 40 microL of 4 mM luminol at the patients'
      first visits. All of the participants were inquired about their partners'
      pregnancies after the mean follow-up of 24.0 months (range 1.4 to 74.1). They
      were divided into two groups (pregnant group: n = 41, non-pregnant group: n = 48)
      and their characteristics, semen profiles and integrated ROS levels were
      analyzed. RESULTS: There was no difference between the pregnancy rate of ROS
      detectable cases and negative cases. However, the mean integrated ROS level in
      detectable cases of the non-pregnant group was significantly higher than that in
      detectable cases of the pregnant group (115.61 +/- 74.32 mV/30 min/10(6) sperm
      versus 7.22 +/- 4.69 mV/30 min/10(6) sperm, P = 0.0033). Then, by calculating the
      receiver operating characteristics curve with 95% confidence intervals, 4.35
      mV/30 min/10(6) sperm was considered as a cut-off value of ROS in semen for
      pregnancy. CONCLUSION: These results indicate that (i) highly detectable ROS in
      whole semen of infertile patients may have implications in their partners'
      pregnancies and that (ii) detection of ROS in whole semen has a prognostic value
      for idiopathic male infertility.

PMID- 19183233
TI  - Purinergic receptor-mediated effects of adenosine 5'-triphosphate in urological
      malignant diseases.
AB  - Adenosine 5'-triphosphate (ATP) mediates a variety of biological functions and
      has been shown to play a physiological role in almost every system in the body.
      In the genito-urinary system, extracellular ATP has been shown to play a
      functional role in several different capacities, ranging from nociception in the
      ureter and bladder, to erectile dysfunction via its action on different
      'purinergic receptors'. Discovery of the trophic effects of ATP has led to a
      surge in interest in this signalling system in various malignancies. To date five
      P2 receptor subtypes have been implicated in the growth inhibition of cancer
      cells, namely P2X5, P2X7, P2Y1, P2Y2 and P2Y11. Limited data are available on
      urological malignancies. ATP induces its anti-neoplastic effect primarily via
      purinergic receptor-mediated apoptosis via calcium-independent pathways, and this
      has been confirmed in vitro and in vivo. Studies have highlighted functional
      roles for the P2X5 and/or P2Y11 receptors in both hormone refractory prostate
      cancer and high-grade bladder cancer, although the contributory effect of pro
      apoptotic P2X7 receptors remains unclear. Clinical trials have shown intravenous
      ATP successfully attenuates a range of systemic symptoms associated with advanced
      malignancies. This raises the possibility that selective targeting of specific
      aberrant pathways may allow for treatment of advanced primary malignancies and
      their systemic effects.

PMID- 19183234
TI  - Trends in radical prostatectomy.
AB  - The surgical treatment of prostate cancer ideally removes the entire cancer,
      avoids excessive blood loss or serious perioperative complications, and results
      in complete recovery of continence and potency. To achieve this, the surgeon must
      excise sufficient periprostatic tissue to cure the cancer while preserving the
      cavernosal nerves required for erectile function and the neuromusculature
      required for normal urinary and bowel function. Here we will examine recent
      trends in radical prostatectomy, focusing on surgical technique.

PMID- 19183235
TI  - Transition shock: the initial stage of role adaptation for newly graduated
      registered nurses.
AB  - AIM: The aim of this paper is to provide a theoretical framework of the initial
      role transition for newly graduated nurses to assist managers, educators and
      seasoned practitioners to support and facilitate this professional adjustment
      appropriately. BACKGROUND: The theory of Transition Shock presented here builds
      on Kramer's work by outlining how the contemporary new graduate engaging in a
      professional practice role for the first time is confronted with a broad range
      and scope of physical, intellectual, emotional, developmental and sociocultural
      changes that are expressions of, and mitigating factors within the experience of
      transition. DATA SOURCES: This paper offers cumulative knowledge gained from a
      programme of research spanning the last 10 years and four qualitative studies on
      new graduate transition. DISCUSSION: New nurses often identify their initial
      professional adjustment in terms of the feelings of anxiety, insecurity,
      inadequacy and instability it produces. The Transition Shock theory offered
      focuses on the aspects of the new graduate's roles, responsibilities,
      relationship and knowledge that both mediate the intensity and duration of the
      transition experience and qualify the early stage of professional role transition
      for the new nursing graduate. CONCLUSION: Transition shock reinforces the need
      for preparatory theory about role transition for senior nursing students and the
      critical importance of bridging undergraduate educational curricula with
      escalating workplace expectations. The goal of such knowledge is the successful
      integration of new nursing professionals into the stressful and highly dynamic
      context of professional practice.

PMID- 19183236
TI  - Identifying abuse among women: use of clinical guidelines by nurses and midwives.
AB  - AIM: This aim of this study to identify the incidence of violence against women
      seeking healthcare services and evaluate the use of clinical guidelines to
      identify interpersonal violence. METHODS: A cross-sectional survey was carried
      out. Data were collected over a period of 7 months in 2005 and 2006. The samples
      consisted of 14 nurses, 10 midwives and 208 women in Iceland (101 women visiting
      the Emergency Department and 107 receiving prenatal care at the High Risk
      Prenatal Care Clinic). RESULTS: Twenty women (19.6%) who visited the Emergency
      Department and 21 women (19.8%) who came to the High Risk Prenatal Care Clinic
      had been sexually abused at some point in their lives by close family members.
      Within the preceding 12 months, 18 women at the Emergency Department (19.1%) and
      eight at the High Risk Prenatal Care Clinic (7.5%) reported physical abuse, and
      22 women (22.2%) at the Emergency Department and 12 (11.5%) at the High Risk
      Prenatal Care Clinic reported emotional abuse. A majority of the nurses and
      midwives indicated that the guidelines were efficient for assessing/screening for
      gender violence in emergency and high risk clinical settings. CONCLUSION:
      Screening for abuse of women at emergency and high risk clinics is crucial, not
      only to offer the women the immediate interventions they might need, but also to
      ensure the future provision of appropriate healthcare services.

PMID- 19183237
TI  - A new era for small molecule screening: from new targets, such as JAK2 V617F, to
      complex cellular screens.
AB  - Traditionally reserved to research and development in pharmaceutical companies,
      screening of small molecule libraries is rapidly becoming an approach undertaken
      by academic laboratories. Novel cellular assays, sensitive systems to probe
      function, emerging new molecular targets are just some of the reasons explaining
      this shift. Targets of small molecules identified in cellular screens begin to be
      amenable to identification by elegant genetic approaches, such as probing
      toxicity of candidate small molecules on libraries of genetically modified yeast
      strains. Several new targets, such as JAK2 V617F, an activated JAK2 (Janus Kinase
      2) mutant genetically associated with the majority of human myeloproliferative
      neoplasms, are being actively pursued. In this Review Series, we will learn how
      libraries of small molecules are harnessed to identify novel molecules, that
      alone or in combination, have the ability to alter cell fate, cell signalling,
      gene expression or response to extracellular cues.

PMID- 19183238
TI  - Docking, virtual high throughput screening and in silico fragment-based drug
      design.
AB  - The drug discovery process has been profoundly changed recently by the adoption
      of computational methods helping the design of new drug candidates more rapidly
      and at lower costs. In silico drug design consists of a collection of tools
      helping to make rational decisions at the different steps of the drug discovery
      process, such as the identification of a biomolecular target of therapeutical
      interest, the selection or the design of new lead compounds and their
      modification to obtain better affinities, as well as pharmacokinetic and
      pharmacodynamic properties. Among the different tools available, a particular
      emphasis is placed in this review on molecular docking, virtual high-throughput
      screening and fragment-based ligand design.

PMID- 19183241
TI  - Avoiding lentiviral transduction culture induced MSC senescence.

PMID- 19183242
TI  - Regulatory T cells and their prognostic value for patients with squamous cell
      carcinoma of the head and neck.
AB  - Regulatory T cells (Treg) are important regulators of anti-cancer immune
      responses, and an increase in Treg frequency was observed in the blood of cancer
      patients. Blood samples from 112 patients with head and neck squamous cell
      carcinoma antigen (HNSCC) were obtained at the time of tumour diagnosis, and
      lymphocyte subpopulations (CD3(+); CD3(-)CD16(+)CD56(+); CD4(+); CD8(+); CD19(+);
      CD4(+)CD45RA(+)) with emphasis on Treg counts (CD3(+)CD4(+)CD25(+)), complete
      blood count and tumour markers (squamous cell carcinoma [SCC]; CEA; alpha-1
      antitrypsin [AAT]; Cyfra 21-1; C-reactive protein [CRP]) were analysed. The data
      were grouped according to TNM classification, and their significance for the
      course of the disease at an interval of 1 year after the end of the therapy was
      determined. The percentage of CD8(+) cells increased and the CD/D8 ratio
      decreased with tumour grade. The ratio of B lymphocytes decreased in patients
      with locoregional metastases (11.25%versus 9.22%). Treg (15.2%) and CD4(+) cells
      (45.3%) increased, while NK cells (11.8%) decreased in HNSCC patients compared to
      controls (9.0%, 38.1% and 15.8%, respectively). The data obtained at time of
      diagnosis were used to assess the significance of tumour markers (SCC, Cyfra 21-1
      and AAT) for evaluation of prognosis. The erythrocyte counts (4.64 x 10(12)/l
      versus 4.45 x 10(12)/l) and haemoglobin levels (14.58 g/dl versus 14.05 g/dl)
      decreased, while Treg counts (8.91%versus 15.70%) increased in patients with
      early recurrence. Our results show that examination of these parameters could be
      helpful for prognostication in HNSCC patients and aid improvement of treatment
      strategy.

PMID- 19183244
TI  - A novel protein fraction from Sesbania grandiflora shows potential anticancer and
      chemopreventive efficacy, in vitro and in vivo.
AB  - We report mechanism-based evidence for the anticancer efficacy of a protein
      fraction, SF2 (Sesbania fraction 2) isolated from the flower of the medicinal
      plant, Sesbania grandiflora (S. grandiflora). The fraction was evaluated in two
      murine ascites tumour cell lines and human cancer cell lines of different origin
      for its anticancer effect. SF2 inhibited cell proliferation and induced apoptosis
      as demonstrated by DNA fragmentation and externalization of phosphatidyl serine
      in Daltons lymphoma ascites (DLA) and colon cancer cells (SW-480). Sensitivity to
      SF2 in these cells was associated with activation of caspases 3, 8 and 9, poly
      (ADP-ribose) polymerase cleavage and cytochrome C release which attests apoptosis
      induced cell death. Mechanistically, SF2 down-regulated phorbol myristate acetate
      (PMA) induced NF-kappaB, a transcription factor which controls the expression of
      genes encoding proteins involved in cell regulation and growth control.
      Additionally, SF2 also down-regulated anti-apoptotic factors such as Bcl-2, p-Akt
      and cyclooxygenase-2 induced by the tumour promoter PMA suggestive of a possible
      explanation for its anticancer effect. In vivo studies using ascites and solid
      tumour models strongly support in vitro findings as SF2 administration increased
      the life span and decreased the tumour volume in mice bearing tumour. In vivo
      toxicological evaluation revealed the pharmacological safety of SF2 and may serve
      as a potential anticancer drug candidate.

PMID- 19183246
TI  - Machine learning approach identifies new pathways associated with demyelination
      in a viral model of multiple sclerosis.
AB  - Theiler's murine encephalomyelitis is an experimentally virus-induced
      inflammatory demyelinating disease of the spinal cord, displaying clinical and
      pathological similarities to chronic progressive multiple sclerosis. The aim of
      this study was to identify pathways associated with chronic demyelination using
      an assumption-free combined microarray and immunohistology approach. Movement
      control as determined by rotarod assay significantly worsened in Theiler's murine
      encephalomyelitis -virus-infected SJL/J mice from 42 to 196 days after infection
      (dpi). In the spinal cords, inflammatory changes were detected 14 to 196 dpi, and
      demyelination progressively increased from 42 to 196 dpi. Microarray analysis
      revealed 1001 differentially expressed genes over the study period. The
      dominating changes as revealed by k-means and functional annotation clustering
      included up-regulations related to intrathecal antibody production and antigen
      processing and presentation via major histocompatibility class II molecules. A
      random forest machine learning algorithm revealed that down-regulated lipid and
      cholesterol biosynthesis, differentially expressed neurite morphogenesis and up
      regulated toll-like receptor-4-induced pathways were intimately associated with
      demyelination as measured by immunohistology. Conclusively, although
      transcriptional changes were dominated by the adaptive immune response, the main
      pathways associated with demyelination included up-regulation of toll-like
      receptor 4 and down-regulation of cholesterol biosynthesis. Cholesterol
      biosynthesis is a rate limiting step of myelination and its down-regulation is
      suggested to be involved in chronic demyelination by an inhibition of
      remyelination.

PMID- 19183249
TI  - Proteomic analysis reveals novel binding partners of metabotropic glutamate
      receptor 1.
AB  - Regulated trafficking of neurotransmitter receptors is critical to normal
      neurodevelopment and neuronal signaling. Group I mGluRs (mGluR1/5 and their
      splice variants) are G protein-coupled receptors enriched at excitatory synapses,
      where they serve to modulate glutamatergic transmission. The mGluR1 splice
      variants mGluR1a and mGluR1b are broadly expressed in the central nervous system
      and differ in their signaling and trafficking properties. Several proteins have
      been identified that selectively interact with mGluR1a and participate in
      receptor trafficking but no proteins interacting with mGluR1b have thus far been
      reported. We have used a proteomic strategy to isolate and identify proteins that
      co-purify with mGluR1b in Madin-Darby Canine Kidney (MDCK) cells, an established
      model system for trafficking studies. Here, we report the identification of 10
      novel candidate mGluR1b-interacting proteins. Several of the identified proteins
      are structural components of the cell cytoskeleton, while others serve as
      cytoskeleton-associated adaptors and motors or endoplasmic reticulum-associated
      chaperones. Findings from this work will help unravel the complex cellular
      mechanisms underlying mGluR trafficking under physiological and pathological
      conditions.

PMID- 19183250
TI  - Angiotensin-(1-7) through AT receptors mediates tyrosine hydroxylase degradation
      via the ubiquitin-proteasome pathway.
AB  - Hypothalamic norepinephrine (NE) release regulates arterial pressure by altering
      sympathetic nervous system activity. Because angiotensin (Ang) (1-7) decreases
      hypothalamic NE release and this effect may be correlated with a diminished NE
      synthesis, we hypothesize that Ang-(1-7) down-regulates tyrosine hydroxylase
      (TH), the rate-limiting enzyme in catecholamines biosynthesis. We investigated
      the effect of Ang-(1-7) on centrally TH activity and expression. TH activity was
      evaluated by the release of tritiated water from (3)H-l-tyrosine. TH expression
      and phosphorylation were determined by western blot. Hypothalami from
      normotensive or spontaneously hypertensive rats pre-incubated with Ang-(1-7)
      showed a significant decrease in TH specific activity. Ang-(1-7) caused a
      decrease in TH phosphorylation at Ser19 and Ser40 residues. The heptapeptide
      induced a decrease in TH expression that was blocked by an AT(2) receptor
      antagonist and not by an AT(1) or Mas receptor antagonist, suggesting the
      involvement of AT(2) receptors. The proteasome inhibitor MG132 blocked the Ang-(1
      7)-mediated TH reduction. In addition, Ang-(1-7) increased the amount of TH
      ubiquitin complexes, indicating that the Ang-(1-7)-mediated TH degradation
      involves ubiquitin conjugation prior to proteasome degradation. We conclude that
      Ang-(1-7) down-regulates TH activity and expression centrally leading to a
      decrease in the central NE system activity.

PMID- 19183252
TI  - Rapid substrate-induced down-regulation in function and surface localization of
      dopamine transporters: rat dorsal striatum versus nucleus accumbens.
AB  - The dopamine transporter (DAT) substrates dopamine, d-amphetamine (AMPH), and
      methamphetamine are known to rapidly and transiently reduce DAT activity and/or
      surface expression in dorsal striatum and heterologous expression systems. We
      sought to determine if similar substrate-induced regulation of DATs occurs in rat
      nucleus accumbens. In dorsal striatum synaptosomes, brief (15-min) in vitro
      substrate pre-exposure markedly decreased maximal [(3)H]dopamine uptake velocity
      whereas identical substrate pre-exposure in nucleus accumbens synaptosomes
      produced a smaller, non-significant reduction. However, 45 min after systemic
      AMPH administration, maximal ex vivo [(3)H]dopamine uptake velocity was
      significantly reduced in both brain regions. Protein kinase C inhibition blocked
      AMPH's down-regulation of DAT activity. DAT synaptosomal surface expression was
      not modified following either the brief in vitro or in vivo AMPH pre-exposure but
      was reduced after a longer (1-h) in vitro pre-exposure in both brain regions.
      Together, our findings suggest that relatively brief substrate exposure results
      in greater down-regulation of DAT activity in dorsal striatum than in nucleus
      accumbens. Moreover, exposure to AMPH appears to regulate striatal DATs in a
      biphasic manner, with an initial protein kinase C-dependent decrease in DAT
      mediated uptake velocity and then, with longer exposure, a reduction in DAT
      surface expression.

PMID- 19183251
TI  - Behavioral sensitization to amphetamine is not accompanied by changes in
      glutamate receptor surface expression in the rat nucleus accumbens.
AB  - We examined whether behavioral sensitization to amphetamine is associated with
      redistribution of glutamate receptors (GluR) in the rat nucleus accumbens (NAc)
      or dorsolateral striatum (DLSTR). Following repeated amphetamine treatment and 21
      days of withdrawal, surface and intracellular levels of alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate (AMPA) or NMDA receptor subunits were determined
      using a protein cross-linking assay. In contrast to our previous results in
      cocaine-sensitized rats, we did not observe redistribution of GluR1 or GluR2 to
      the cell surface in the NAc after amphetamine withdrawal, although a small
      increase in total GluR1 was found in the shell subregion. Nor did we observe
      activation of signaling pathways associated with cocaine-induced AMPA receptor
      trafficking or changes in NMDA receptor subunits. No significant changes were
      observed in the DLSTR. We also investigated the effect of administering a
      challenge injection of amphetamine to amphetamine-sensitized rats 24 h prior to
      biochemical analysis based on prior studies showing that cocaine challenge
      decreases AMPA receptor surface expression in the NAc of cocaine-sensitized rats.
      GluR1 and GluR2 were not significantly altered in either NAc or DLSTR, although a
      modest effect on GluR3 cannot be ruled out. Our results suggest that glutamate
      transmission in the NAc is dramatically different in rats sensitized to
      amphetamine versus cocaine.

PMID- 19183253
TI  - Roles of protein kinase Calpha isozyme in the regulation of oxidative stress and
      neuropeptide Y gene expression in phenylpropanolamine-mediated appetite
      suppression.
AB  - Hypothalamic neuropeptide Y (NPY) is an appetite stimulant in the brain. Although
      regulation of NPY expression has been reported to contribute to the appetite
      suppressing effect of phenylpropanolamine (PPA), it is still unknown if protein
      kinase C (PKC) is involved in this effect. Rats were daily treated with PPA for 4
      days. Changes in food intake, hypothalamic NPY, PKC, and proopiomelanocortin
      (POMC) mRNA levels were assessed and compared. Results showed that the NPY gene
      was down-regulated following PPA treatment, which was parallel with the decrease
      of feeding. Moreover, several isotypes of PKC mRNA level (alpha, betaI, betaII,
      gamma, delta, eta, lambda, epsilon, and zeta) were changed. Among these, alpha,
      delta, and lambda PKC were up-regulated along with POMC gene expression which
      coincided with down-regulation of the NPY gene. To further determine if PKCalpha
      was involved, infusions of antisense oligonucleotide into the cerebroventricle
      were performed at 1 h before daily PPA treatment in free-moving rats. Results
      showed that PKCalpha knock-down could modify both anorexia induced by PPA and the
      NPY mRNA levels. Moreover, PKCalpha knock-down could also modify superoxide
      dismutase (SOD) gene expression. It is suggested that PKCalpha participates in
      the regulation of PPA-mediated appetite suppression via the modulation of NPY and
      SOD gene expression.

PMID- 19183254
TI  - Curcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and
      neurons: importance of the glutamate cysteine ligase modifier subunit.
AB  - A decrease in GSH levels, the main redox regulator, can be observed in
      neurodegenerative diseases as well as in schizophrenia. In search for substances
      able to increase GSH, we evaluated the ability of curcumin (polyphenol),
      quercetin (flavonoid), and tert-butylhydroquinone (tBHQ) to up-regulate GSH
      synthesizing enzymes. The gene expression, activity, and product levels of these
      enzymes were measured in cultured neurons and astrocytes. In astrocytes, all
      substances increased GSH levels and the activity of the rate-limiting
      synthesizing enzyme, glutamate cysteine ligase (GCL). In neurons, curcumin and to
      a lesser extent tBHQ increased GCL activity and GSH levels, while quercetin
      decreased GSH and led to cell death. In the two cell types, the gene that showed
      the greatest increase in its expression was the one coding for the modifier
      subunit of GCL (GCLM). The increase in mRNA levels of GCLM was 3 to 7-fold higher
      than that of the catalytic subunit. In astrocytes from GCLM-knock-out mice
      showing low GSH (-80%) and low GCL activity (-50%), none of the substances
      succeeded in increasing GSH synthesis. Our results indicate that GCLM is
      essential for the up-regulation of GCL activity induced by curcumin, quercetin
      and tBHQ.

PMID- 19183255
TI  - A disintegrin and metalloproteinase (ADAM)-mediated ectodomain shedding of
      ADAM10.
AB  - A disintegrin and metalloproteinase (ADAM) 10 is a type I transmembrane
      glycoprotein responsible for the ectodomain shedding of a range of proteins
      including the amyloid precursor protein implicated in Alzheimer's disease. In
      this study we demonstrate that ADAM10 itself is subject to shedding by one or
      more ADAMs. Expression of epitope-tagged wild-type ADAM10 in SH-SY5Y cells
      enabled the detection of a soluble ectodomain in conditioned medium. Shedding of
      the ADAM10 ectodomain was inhibited by a known ADAM inhibitor with a reciprocal
      accumulation of the full-length mature protein in both cell lysates and
      extracellular membrane vesicles. Shedding was also stimulated by phorbol ester
      treatment of cells. A glycosylphosphatidylinositol-anchored form of ADAM10
      lacking the cytosolic, transmembrane and alpha-helical juxtamembrane regions of
      the wild-type protein was shed in a similar manner. Furthermore, a truncated
      soluble ADAM10 construct, although correctly post-translationally processed and
      catalytically active against a synthetic peptide substrate, was incapable of
      shedding cell-associated amyloid precursor protein. Finally, we show that ADAM9
      is, at least in part, responsible for the ectodomain shedding of ADAM10. In
      conclusion, this is a new mechanism by which levels of ADAM10 are regulated and
      may have implications in a range of human diseases including Alzheimer's disease.

PMID- 19183256
TI  - Lithium induces clearance of protease resistant prion protein in prion-infected
      cells by induction of autophagy.
AB  - Lithium is used for several decades to treat manic-depressive illness (bipolar
      affective disorder). Recently, it was found that lithium induces autophagy,
      thereby promoting the clearance of mutant huntingtin and alpha-synucleins in
      experimental systems. We show here for the first time that lithium significantly
      reduces the amount of pathological prion protein (PrP(Sc)) in prion-infected
      neuronal and non-neuronal cultured cells by inducing autophagy. Treatment of
      prion-infected cells with 3-methyladenine, a potent inhibitor of autophagy,
      counteracted the anti-prion effect of lithium, demonstrating that induction of
      autophagy mediates degradation of PrP(Sc). Co-treatment with lithium and
      rapamycin, a drug widely used to induce autophagy, had an additive effect on
      PrP(Sc) clearance compared to treatment with either drug alone. In addition, we
      provide evidence that the ability to reduce PrP(Sc) and to induce autophagy is
      common for diverse lithium compounds, not only for the drug lithium chloride,
      usually administered in clinical therapy. Furthermore, we show here that besides
      reduction of PrP(Sc)-aggregates, lithium-induced autophagy also slightly reduces
      the levels of cellular prion protein. Limiting the substrate available for
      conversion of cellular prion protein into PrP(Sc) may provide an additional
      mechanism for reduction of PrP(Sc) by lithium-induced autophagy.

PMID- 19183257
TI  - Dopamine transporter relation to levodopa-derived synaptic dopamine in a rat
      model of Parkinson's: an in vivo imaging study.
AB  - Studies showed that the dopamine (DA) transporter (DAT) modulates changes in
      levodopa-derived synaptic dopamine levels (Delta(DA)) in Parkinson's disease
      (PD). Here we evaluate the relationship between DAT and Delta(DA) in the 6
      hydroxydopamine model of Parkinson's disease to investigate these mechanisms as a
      function of dopaminergic denervation and in relation to other denervation-induced
      regulatory changes. 27 rats with a unilateral 6-hydroxydopamine lesion
      (denervation approximately 20-97%) were imaged with (11)C-dihydrotetrabenazine
      (VMAT2 marker), (11)C-methylphenidate (DAT marker) and (11)C-raclopride (D2-type
      receptor marker). For denervation <75%Delta(DA) was significantly correlated with
      a combination of relatively preserved terminal density and lower DAT. For
      denervation <90%, Delta(DA) was significantly negatively correlated with DAT with
      a weaker dependence on VMAT2. For the entire data set, no dependence on pre
      synaptic markers was observed; Delta(DA) was significantly positively correlated
      with (11)C-raclopride binding-derived estimates of DA loss. These findings
      parallel observations in humans, and show that (i) regulatory changes attempt to
      normalize synaptic DA levels (ii) a lesion-induced functional dependence of
      Delta(DA) on DAT occurs up to approximately 90% denervation (iii) for denervation
      < 75% relative lower DAT levels may relate to effective compensation; for higher
      denervation, lower DAT levels likely contribute to oscillations in synaptic DA
      associated with dyskinesias.

PMID- 19183258
TI  - U18666A, a cholesterol-inhibition agent, modulates human neuronal nicotinic
      acetylcholine receptors heterologously expressed in SH-EP1 cell line.
AB  - In this study, we evaluate the effects of (3beta)-3-[2
      (diethylamino)ethoxy]androst-5-en-17-one dihydrochloride (U18666A), a cholesterol
      synthesis/transporter inhibitor, on selected human neuronal nicotinic
      acetylcholine receptors (nAChRs) heterologously expressed in the SH-EP1 cell line
      using whole-cell patch-clamp recordings. The results indicate that with 2-min
      pretreatment, U18666A inhibited different nAChR subtypes with a rank-order of
      potency (IC(50) of whole-cell peak current): alpha4beta2 (8.0 +/- 3.0 nM) >
      alpha3beta2 (1.7 +/- 0.4 microM) > alpha4beta4 (26 +/- 7.2 microM) > alpha7 (>
      100 microM), suggesting this compound is more selective to alpha4beta2-nAChRs.
      Thus, the pharmacological profiles and mechanisms of U18666A acting on
      alpha4beta2-nAChRs were investigated in detail. U18666A suppresses both peak and
      steady state components of whole-cell currents mediated by human alpha4beta2
      nAChRs in response to nicotine. In nicotine-induced concentration-response
      curves, U18666A reduces nicotine-induced current at maximally effective agonist
      concentrations without influencing nicotine's EC(50) value, suggesting a non
      competitive inhibition. U18666A-induced inhibition of nAChR function is
      concentration-, voltage-, and use-dependent, suggesting an open channel block.
      Taken into consideration of approximately 10 000-fold enhancement of the potency
      of U18666A after 2-min pre-treatment, this compound also likely inhibits
      alpha4beta2-nAChRs through a close channel block. In addition, the U18666A
      induced inhibition in alpha4beta2-nAChRs is not mediated by either increased
      receptor endocytosis or altered cell cholesterol. These data indicate that
      U18666A is a potent antagonist of alpha4beta2-nAChRs and may be useful as a tool
      in the functional characterization and pharmacological profiling of nAChRs, as
      well as a potential candidate for smoking cessation.

PMID- 19183259
TI  - Lithium enhances the neuronal differentiation of neural progenitor cells in vitro
      and after transplantation into the avulsed ventral horn of adult rats through the
      secretion of brain-derived neurotrophic factor.
AB  - This study was undertaken to elucidate the molecular mechanisms by which lithium
      regulates the development of spinal cord-derived neural progenitor cells (NPCs)
      in vitro and after transplanted in vivo. Our results show that lithium at the
      therapeutic concentration significantly increases the proliferation and neuronal
      differentiation of NPCs in vitro. Specific ELISAs, western blotting, and
      quantitative real-time RT-PCR assays demonstrate that lithium treatment
      significantly elevates the expression and production of brain-derived
      neurotrophic factor (BDNF) by NPCs in culture. Application of a BDNF neutralizing
      antibody in culture leads to a marked reduction in the neurogenesis of lithium
      treated NPCs to the control level. However, it shows no effects on the
      proliferation of lithium-treated NPCs. These findings suggest that the BDNF
      pathway is possibly involved in the supportive role of lithium in inducing NPC
      neurogenesis but not proliferation. This study also provides evidence that
      lithium is able to elevate the neuronal generation and BDNF production of NPCs
      after transplantation into the adult rat ventral horn with motoneuron
      degeneration because of spinal root avulsion, which highlights the therapeutic
      potential of lithium in cell replacement strategies for spinal cord injury
      because of its ability to promote neuronal differentiation and BDNF production of
      grafted NPCs in the injured spinal cord.

PMID- 19183260
TI  - Chronic copper exposure exacerbates both amyloid and tau pathology and
      selectively dysregulates cdk5 in a mouse model of AD.
AB  - Excess copper exposure is thought to be linked to the development of Alzheimer's
      disease (AD) neuropathology. However, the mechanism by which copper affects the
      CNS remains unclear. To investigate the effect of chronic copper exposure on both
      beta-amyloid and tau pathologies, we treated young triple transgenic (3xTg-AD)
      mice with 250 ppm copper-containing water for a period of 3 or 9 months. Copper
      exposure resulted in altered amyloid precursor protein processing; increased
      accumulation of the amyloid precursor protein and its proteolytic product, C99
      fragment, along with increased generation of amyloid-beta peptides and oligomers.
      These changes were found to be mediated via up-regulation of BACE1 as significant
      increases in BACE1 levels and deposits were detected around plaques in mice
      following copper exposure. Furthermore, tau pathology within hippocampal neurons
      was exacerbated in copper-exposed 3xTg-AD group. Increased tau phosphorylation
      was closely correlated with aberrant cdk5/p25 activation, suggesting a role for
      this kinase in the development of copper-induced tau pathology. Taken together,
      our data suggest that chronic copper exposure accelerates not only amyloid
      pathology but also tau pathology in a mouse model of AD.

PMID- 19183261
TI  - Sonic Hedgehog signaling in astrocytes is dependent on p38 mitogen-activated
      protein kinase and G-protein receptor kinase 2.
AB  - The molecular determinants of Sonic Hedgehog (Shh) signaling in mammalian cells
      and, in particular, those of the CNS are unclear. Here we report that primary
      cortical astrocyte cultures are highly responsive to both Shh protein and Hh
      Agonist 1.6, a selective, small molecule Smoothened agonist. Both agonists
      produced increases in mRNA expression of Shh-regulated gene targets, Gli-1 and
      Patched in a cyclopamine- and forskolin-sensitive manner. Using this model we
      show for the first time that Shh pathway activation mediates rapid increases in
      p38 MAPK phosphorylation, without altering phosphorylation of either
      extracellular-signal-regulated kinases or c-jun N-terminal kinases. Selective
      inhibition of p38 MAPK significantly attenuated Shh-dependent up-regulation of
      Gli-1, inter-alpha trypsin inhibitor and thrombomodulin mRNA, however did not
      affect expression of insulin-like growth factor 2 or a novel Shh target, membrane
      associated guanylate kinase p55 subfamily member 6. Using RNAi and a
      constitutively-active mutant we show that Shh signaling to p38 MAPK and
      subsequent Gli-1 transcription requires G-protein receptor kinase 2. Taken
      together, these findings provide evidence for a central role of G-protein
      receptor kinase 2-dependent p38 MAPK activity in regulating Shh-mediated gene
      transcription in astrocytes.

PMID- 19183262
TI  - Absence of endogenous interleukin-10 enhances secondary inflammatory process
      after spinal cord compression injury in mice.
AB  - Interleukin-10 (IL-10) exerts a wide spectrum of regulatory activities in the
      immune and inflammatory response. The aim of this study was to investigate the
      role of endogenous IL-10 on the modulation of the secondary events in mice
      subjected to spinal cord injury induced by the application of vascular clips
      (force of 24 g) to the dura via a four-level T5-T8 laminectomy. IL-10 wild-type
      mice developed severe spinal cord damage characterized by oedema, tissue damage
      and apoptosis (measured by Annexin-V, terminal deoxynucleotidyltransferase
      mediated UTP end labeling staining, Bax, Bcl-2, and Fas-L expression).
      Immunohistochemistry demonstrated a marked increase of localization of TNF-alpha,
      IL-1beta and S100beta, while western blot analysis shown an increased
      immunoreactivity of inducible nitric oxide synthase in the spinal cord tissues.
      The absence of IL-10 in IL-10 KO mice resulted in a significant augmentation of
      all the above described parameters. We have also demonstrated that the genetic
      absence of IL-10 worsened the recovery of limb function when compared with IL-10
      wild-type mice group (evaluated by motor recovery score). Taken together, our
      results clearly demonstrate that the presence of IL-10 reduces the development of
      inflammation and tissue injury events associated with spinal cord trauma.

PMID- 19183263
TI  - Altered CB receptor-signaling in prefrontal cortex from an animal model of
      depression is reversed by chronic fluoxetine.
AB  - Bilateral olfactory bulbectomy in the rat (OBX) induces behavioral,
      neurochemical, and structural abnormalities similar to those observed in human
      depression that are normalized after chronic, but not acute, treatment with
      antidepressants. In our study, OBX animals exhibited significant increases in
      both CB(1) receptor density ([(3)H]CP55490 binding) and functionality
      (stimulation of [(35)S]GTPgammaS binding by the cannabinoid (CB) agonist WIN
      55212-2) at the prefrontal cortex (PFC). After chronic treatment with fluoxetine
      (10 mg/kg/day, 14 days, s.c.), OBX-induced hyperactivity in the open-field test
      was fully abolished. Interestingly, chronic fluoxetine fully reversed the
      enhanced CB(1)-receptor signaling in PFC observed following OBX. The CB agonist
      Delta(9)-tetrahydrocannabinol (5 mg/kg, i.p., 1 day) did not produce any
      behavioral effect in sham-operated animals but returned locomotor activity to
      control values in OBX rats. As both acute administration of Delta(9)
      tetrahydrocannabinol and chronic fluoxetine elicited a similar behavioral effect
      in the OBX rat, it is not unlikely that the regionally selective enhancement of
      CB(1) receptor-signaling in the PFC could be related with the altered OBX
      behavior. Our findings reinforce the utility of this animal model to further
      investigating the implication of the endocannabinoid system in the modulation of
      emotional processes and its potential role in the adaptive responses to chronic
      antidepressants.

PMID- 19183264
TI  - ALS-linked P56S-VAPB, an aggregated loss-of-function mutant of VAPB, predisposes
      motor neurons to ER stress-related death by inducing aggregation of co-expressed
      wild-type VAPB.
AB  - A point mutation (P56S) in the vapb gene encoding an endoplasmic reticulum (ER)
      integrated membrane protein [vesicle-associated membrane protein-associated
      protein B (VAPB)] causes autosomal-dominant amyotrophic lateral sclerosis. In our
      earlier study, we showed that VAPB may be involved in the IRE1/XBP1 signaling of
      the unfolded protein response, an ER reaction to inhibit accumulation of
      unfolded/ misfolded proteins, while P56S-VAPB formed insoluble aggregates and
      lost the ability to mediate the pathway (lossof- function), and suggested that
      P56S-VAPB promoted the aggregation of co-expressed wild-type (wt)-VAPB. In this
      study, a yeast inositol-auxotrophy assay has confirmed that P56S-VAPB is
      functionally a null mutant in vivo. The interaction between P56S-VAPB and wt-VAPB
      takes place with a high affinity through the major sperm protein domain in
      addition to the interaction through the C-terminal transmembrane domain.
      Consequently, wt-VAPB is speculated to preferentially interact with co-expressed
      P56S-VAPB, leading to the recruitment of wt-VAPB into cytosolic aggregates and
      the attenuation of its normal function. We have also found that expression of
      P56S-VAPB increases the vulnerability of NSC34 motoneuronal cells to ER stress
      induced death. These results lead us to hypothesize that the total loss of VAPB
      function in unfolded protein response, induced by one P56S mutant allele, may
      contribute to the development of P56SVAPB- induced amyotrophic lateral sclerosis.

PMID- 19183265
TI  - HSP70 interacting protein prevents the accumulation of inclusions in
      polyglutamine disease.
AB  - Heat shock proteins (HSPs) are associated with the proteinaceous inclusions that
      characterise many neurodegenerative diseases. This suggests they may be
      associated with disease aetiology and/or represents an attempt to remove abnormal
      protein aggregates. In this study the adenoviral mediated over-expression of
      HSP70 interacting protein (HIP) alone was shown to significantly reduce inclusion
      formation in both an in vitro model of Spinal Bulbar Muscular Atrophy and a
      primary neuronal model of polyglutamine disease. Experiments to determine the
      mechanism of action showed that: denatured luciferase activity (a measure of
      protein refolding) was not increased in the presence of HIP alone but was
      increased when HIP was co-expressed with HSP70 or Heat Shock cognate protein 70
      (HSC70); the expression of polyglutamine inclusions in cortical neurons mediated
      an increase in the levels of HSC70 but not HSP70. Our data suggest that HIP may
      prevent inclusion formation by facilitating the constitutive HSC70 refolding
      cycle and possibly by preventing aggregation. HIP expression is not increased
      following stress and its over-expression may therefore reduce toxic polyglutamine
      aggregation events and contribute to an effective therapeutic strategy.

PMID- 19183266
TI  - CREB activation in the rapid, intermediate, and delayed ischemic preconditioning
      against hypoxic-ischemia in neonatal rat.
AB  - Ischemic preconditioning (IP) is a defense program in which exposure to sublethal
      ischemia followed by a period of reperfusion results in subsequent resistance to
      severe ischemic insults. Very few in vivo IP models have been established for
      neonatal brain. We examined whether rapid, intermediate, and delayed IP against
      hypoxic-ischemia (HI) could be induced in neonatal brain, and if so, whether the
      IP involved phosphorylation of cAMP response element-binding protein (pCREB)
      after HI. Postnatal day 7 rat pups were subjected to HI at 2 h (2-h IP), 6 h (6-h
      IP), or 22 h (22-h IP) after IP. We found all three IP groups had significantly
      reduced neuronal damage and TUNEL-(+) cells 24 h post-HI than no-IP group.
      Compared with control, the no-IP group had significant decreases of pCREB and
      mitochondria Bcl-2 levels in the ipsilateral cortex 24 h post-HI. In contrast,
      the three IP groups had increased pCREB and mitochondria Bcl-2 levels, and
      significant differences were found between three IP and no-IP groups. The
      increases of cleavage of caspase-3 and poly (ADP-ribose) polymerase and of cells
      with nuclear apoptosis inducing factor post-HI in no-IP group were all
      significantly reduced in three IP groups. The increases of caspase-3 and calpain
      mediated proteolysis of a-spectrin post-HI were significantly reduced only in 22
      h IP group. Furthermore, all three IP groups had long-term neuroprotection at
      behavioral and pathological levels compared with no-IP group. In conclusion, IP,
      rapid, intermediate, or delayed, in neonatal rat brain activates CREB, up
      regulates Bcl-2, induces extensive brakes on caspase-dependent and -independent
      apoptosis after HI, and provides long-term neuroprotection.

PMID- 19183267
TI  - The interplay between inorganic phosphate and amino acids determines zinc
      solubility in brain slices.
AB  - Inorganic phosphate (Pi) is an important polyanion needed for ATP synthesis and
      bone formation. As it is found at millimolar levels in plasma, it is usually
      incorporated as a constituent of artificial CSF formulations for maintaining
      brain slices. In this paper, we show that Pi limits the extracellular zinc
      concentration by inducing metal precipitation. We present data suggesting that
      amino acids like histidine may counteract the Pi-induced zinc precipitation by
      the formation of soluble zinc complexes. We propose that the interplay between Pi
      and amino acids in the extracellular space may influence the availability of
      metals for cellular uptake.

PMID- 19183268
TI  - Role of the ERK/MSK1 signalling pathway in chromatin remodelling and brain
      responses to drugs of abuse.
AB  - Drugs of abuse induce neuroadaptations through regulation of gene expression.
      Although much attention has focused on transcription factor activities, new
      concepts have recently emerged on the role of chromatin remodelling as a
      prerequisite for regulation of gene expression in neurons. Thus, for
      transcription to occur, chromatin must be decondensed, a dynamic process that
      depends on post-translational modifications of histones. We review here these
      modifications with a particular emphasis on the role of histone H3
      phosphorylation at the promoter of specific genes, including c-fos and c-jun. We
      trace the signalling pathways involved in H3 phosphorylation and provide evidence
      for a role of mitogen and stress-activated protein kinase-1 (MSK1) downstream
      from the MAPK/extracellular-signal regulated kinase (ERK) cascade. In response to
      cocaine, MSK1 controls an early phase of histone H3 phosphorylation at the c-fos
      promoter in striatal neurons. MSK1 action may be potentiated by the concomitant
      inhibition of protein phosphatase 1 by nuclear translocation of dopamine- and
      cAMP-regulated phosphoprotein Mr = 32 000. H3 phosphorylation by MSK1 is
      critically involved in c-fos transcription, and cocaine-induced locomotor
      sensitization. Thus, ERK plays a dual role in gene regulation and drug addiction
      by direct activation of transcription factors and by chromatin remodelling.

PMID- 19183269
TI  - Specific inhibition of hypoxia inducible factor 1 exaggerates cell injury induced
      by in vitro ischemia through deteriorating cellular redox environment.
AB  - Hypoxia inducible factor 1 (HIF-1) has been suggested to play a critical role in
      the fate of cells exposed to hypoxic stress. However, the mechanism of HIF-1
      regulated cell survival is still not fully understood in ischemic conditions.
      Redox status is critical for decisions of cell survival, death and
      differentiation. We investigated the effects of inhibiting HIF-1 on cellular
      redox status in SH-SY5Y cells exposed to hypoxia or oxygen and glucose
      deprivation (OGD), coupled with cell death analyses. Our results demonstrated
      that inhibiting HIF-1alpha expression by HIF-1alpha specific small interfering
      RNA (siRNA) transfection increased reactive oxygen species generation, and
      transformed the cells to more oxidizing environments (low GSH/GSSG ratio, low
      NADPH level) under either hypoxic or OGD exposure. Cell death increased
      dramatically in the siRNA transfected cells, compared to non-transfected cells
      after hypoxic/OGD exposures. In contrast, increasing HIF-1alpha expression by
      desferrioxamine, a metal chelator and hydroxylase inhibitor, induced a more
      reducing environment (high GSH/GSSG ratio, high NADPH level) and reduced cell
      death. Further studies showed that HIF-1 regulated not only glucose transporter-1
      expression, but also the key enzymes of the pentose phosphate pathway such as
      glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. These
      enzymes are important in maintaining cellular redox homeostasis by generating
      NADPH, the primary reducing agent in cells. Moreover, catalase significantly
      decreased cell death in the siRNA-transfected cells induced by hypoxia and OGD.
      These results suggest that maintenance of cellular redox status by HIF-1 protects
      cells from hypoxia and ischemia mediated injuries.

PMID- 19183270
TI  - Mitigation of peroxynitrite-mediated nitric oxide (NO) toxicity as a mechanism of
      induced adaptive NO resistance in the CNS.
AB  - During CNS injury and diseases, nitric oxide (NO) is released at a high flux rate
      leading to formation of peroxynitrite (ONOO(*)) and other reactive nitrogenous
      species, which nitrate tyrosines of proteins to form 3-nitrotyrosine (3NY),
      leading to cell death. Previously, we have found that motor neurons exposed to
      low levels of NO become resistant to subsequent cytotoxic NO challenge; an effect
      dubbed induced adaptive resistance (IAR). Here, we report IAR mitigates, not only
      cell death, but 3NY formation in response to cytotoxic NO. Addition of an NO
      scavenger before NO challenge duplicates IAR, implicating reactive nitrogenous
      species in cell death. Addition of uric acid (a peroxynitrite scavenger) before
      cytotoxic NO challenge, duplicates IAR, implicating peroxynitrite, with
      subsequent 3NY formation, in cell death, and abrogation of this pathway as a
      mechanism of IAR. IAR is dependent on the heme-metabolizing enzyme, heme
      oxygenase-1 (HO1), as indicated by the elimination of IAR by a specific HO1
      inhibitor, and by the finding that neurons isolated from HO1 null mice have
      increased NO sensitivity with concomitant increased 3NY formation. This data
      indicate that IAR is an HO1-dependent mechanism that prevents peroxynitrite
      mediated NO toxicity in motor neurons, thereby elucidating therapeutic targets
      for the mitigation of CNS disease and injury.

PMID- 19183271
TI  - The essential role of ERK in 4-oxo-2-nonenal-mediated cytotoxicity in SH-SY5Y
      human neuroblastoma cells.
AB  - Lipid peroxidation byproducts, such as 4-hydroxynonenal (HNE) and 4-oxo-2-nonenal
      (ONE), induce cell death in a wide variety of cell types, partly by modulating
      intracellular signaling pathways. However, the specific mechanisms involved,
      particularly for ONE, are unclear while c-Jun N-terminal kinase (JNK) has been
      shown to be essential in HNE-mediated cytotoxicity. In this study, we examined
      the role of mitogen-activated protein kinases signaling pathways in ONE-induced
      cytotoxicity in SH-SY5Y human neuroblastoma cells and found that ONE strongly
      induces the phosphorylation of extracellular signal-regulated kinase (ERK) and
      JNK, but not p38 MAPK. Interestingly, a transient exposure of the cells to ONE
      resulted in cell death, which contrasts with HNE-mediated toxicity. Importantly,
      blocking the ERK pathway, but not the JNK pathway, protected cells against ONE
      induced cytotoxicity indicating a striking difference between the ONE- and HNE
      mediated cytotoxicity mechanisms. Furthermore, inhibition of ERK reduced ONE
      induced phosphorylation of p53, a key modulator of the cellular stress response,
      and the proteolytic cleavage of poly (ADP-ribose) polymerase (PARP), a hallmark
      of apoptosis. Overall, these data strongly suggest that ERK plays an essential
      role in ONE-mediated cytotoxicity and that ERK is an upstream component of p53
      mediated apoptosis.

PMID- 19183273
TI  - X-linked mental retardation: focus on synaptic function and plasticity.
AB  - Among mental disorders, mental retardation has been shown to be caused by various
      factors including a large array of genetic mutations. On the basis of remarkable
      progress, the emerging view is that defects in the regulation of synaptic
      activity and morphogenesis of dendritic spines are apparently common features
      associated with mutations in several genes implicated in mental retardation. In
      this review, we will discuss X-linked MR-related gene products that are
      potentially involved in the normal structure and function of the synapses, with a
      particular focus on pre- and/or post-synaptic plasticity mechanisms. Progress in
      understanding the underlying conditions leading to mental retardation will
      undoubtedly be gained from a closer collaboration of geneticists, physiologists
      and cognitive neuroscientists, which should enable the establishment of
      standardized approaches.

PMID- 19183272
TI  - Developmental regulation of tau phosphorylation, tau kinases, and tau
      phosphatases.
AB  - Tau is a neuronal microtubule-associated protein. Its hyperphosphorylation plays
      a critical role in Alzheimer disease (AD). Expression and phosphorylation of tau
      are regulated developmentally, but its dynamic regulation and the responsible
      kinases or phosphatases remain elusive. Here, we studied the developmental
      regulation of tau in rats during development from embryonic day 15 through the
      age of 24 months. We found that tau expression increased sharply during the
      embryonic stage and then became relatively stable, whereas tau phosphorylation
      was much higher in developing brain than in mature brain. However, the extent of
      tau phosphorylation at seven of the 14 sites studied was much less in developing
      brain than in AD brain. Tau phosphorylation during development matched the period
      of active neurite outgrowth in general. Tau phosphorylation at various sites had
      different topographic distributions. Several tau kinases appeared to regulate tau
      phosphorylation collectively at overlapping sites, and the decrease of overall
      tau phosphorylation in adult brain might be due to the higher levels of tau
      phosphatases in mature brain. These studies provide new insight into the
      developmental regulation of site-specific tau phosphorylation and identify the
      likely sites required for the abnormal hyperphosphorylation of tau in AD.

PMID- 19183274
TI  - Salmonella enterica serotype Typhimurium Std fimbriae bind terminal
      alpha(1,2)fucose residues in the cecal mucosa.
AB  - The std operon encodes a fimbrial adhesin of Salmonella enterica serotype
      Typhimurium that is required for attachment to intestinal epithelial cells and
      for cecal colonization in the mouse. To study the mechanism by which this
      virulence factor contributes to colonization we characterized its binding
      specificity. Std-mediated binding to human colonic epithelial (Caco-2) cells
      could be abrogated by removing N-linked glycans. Adherence of Std fimbriated S.
      Typhimurium to Caco-2 cells could be blocked by co-incubation with H type 2
      oligosaccharide (Fucalpha1-2Galbeta1-4GlcNAc) or by pretreatment of cells with
      alpha1-2 fucosidase. In contrast, pretreatment of Caco-2 cells with neuraminidase
      or co-incubation with the type 2 disaccharide precursor (Galbeta1-4GlcNAc) did
      not reduce adherence of Std fimbriated S. Typhimurium. Binding of purified Std
      fimbriae to Fucalpha1-2Galbeta1-4GlcNAc in a solid phase binding assay was
      competitively inhibited by Ulex europaeus agglutinin-I (UEA-I), a lectin specific
      for Fucalpha1-2 moieties. Purified Std fimbriae and UEA both bound to a receptor
      localized in the mucus layer of the murine cecum. These data suggest that the std
      operon encodes an adhesin that binds an alpha1-2 fucosylated receptor(s) present
      in the cecal mucosa.

PMID- 19183276
TI  - Functional characterization of cohesin SMC3 and separase and their roles in the
      segregation of large and minichromosomes in Trypanosoma brucei.
AB  - Minichromosomes in the nuclear genome of Trypanosoma brucei exhibit unusual
      patterns of mitotic segregation. To address whether differences in their mode of
      segregation in relation to large chromosomes are reflected at a molecular level,
      we characterized two different proteins that have highly conserved functions in
      eukaryotic chromosomes segregation: the SMC3 protein, a component of the
      chromatid cohesion apparatus, and the protease separase that resolves the cohesin
      complex at the onset of anaphase and has, in other organisms, additional
      functions during mitosis. Using in situ hybridization we show that RNA
      interference-mediated depletion of SMC3 has no visible effect on the segregation
      of the minichromosomal population but interferes with the faithful mitotic
      separation of large chromosomes. In contrast, separase depletion causes
      missegregation of both mini- and large chromosomes. We also show that SMC3
      persists as a soluble protein throughout the cell cycle and only associates with
      chromatin between G1 and metaphase. Separase is present in the cell during the
      entire cell cycle, but is excluded from the nucleus until the metaphase-anaphase
      transition, thereby providing a potential control mechanism to prevent the
      untimely cleavage of the cohesin complex.

PMID- 19183275
TI  - Mycoplasma pneumoniae J-domain protein required for terminal organelle function.
AB  - The cell wall-less prokaryote Mycoplasma pneumoniae causes tracheobronchitis and
      primary atypical pneumonia in humans. Colonization of the respiratory epithelium
      requires proper assembly of a complex, multifunctional, polar terminal organelle.
      Loss of a predicted J-domain protein also having domains unique to mycoplasma
      terminal organelle proteins (TopJ) resulted in a non-motile, adherence-deficient
      phenotype. J-domain proteins typically stimulate ATPase activity of Hsp70
      chaperones to bind nascent peptides for proper folding, translocation or
      macromolecular assembly, or to resolve stress-induced protein aggregates. By
      Western immunoblotting all defined terminal organelle proteins examined except
      protein P24 remained at wild-type levels in the topJ mutant; previous studies
      established that P24 is required for normal initiation of terminal organelle
      formation. Nevertheless, terminal organelle proteins P1, P30, HMW1 and P41 failed
      to localize to a cell pole, and when evaluated quantitatively, P30 and HMW1 foci
      were undetectable in >40% of cells. Complementation of the topJ mutant with the
      recombinant wild-type topJ allele largely restored terminal organelle
      development, gliding motility and cytadherence. We propose that this J-domain
      protein, which localizes to the base of the terminal organelle in wild-type M.
      pneumoniae, functions in the late stages of assembly, positioning, or both, of
      nascent terminal organelles.

PMID- 19183278
TI  - Mycolic acid methyltransferase, MmaA4, is necessary for thiacetazone
      susceptibility in Mycobacterium tuberculosis.
AB  - Susceptibility of Mycobacterium tuberculosis to the second-line antitubercular
      drug thiacetazone (TAC) requires activation by the monoxygenase, EthA. Here, we
      report isolation of spontaneous mutants in Mycobacterium bovis BCG that are
      highly resistant to TAC, but carry a functional EthA. Unexpectedly, a majority of
      the TAC-resistant mutants lacked keto-mycolic acids, which are long-chain fatty
      acids associated with the cell wall and which contribute significantly to the
      physiopathology of tuberculosis. Predictably, causative mutations in the above
      mutants were in the gene encoding methyltransferase MmaA4, which is required for
      synthesis of keto- and methoxy-mycolic acids. Drug-resistant phenotype of the BCG
      mutants was reproduced in a mmaA4, but not in a mmaA3 null mutant of M.
      tuberculosis CDC1551. Susceptibility to TAC could be restored by complementation
      with a functional mmaA4 gene. Interestingly, overexpression of MmaA4 in M. bovis
      BCG made it more susceptible to TAC. We provide novel mechanistic insights into
      antitubercular drug activation by co-ordinated actions of EthA and MmaA4. This
      study is the first demonstration of the participation of an enzyme linked to the
      synthesis of oxygenated mycolates in a drug activation process in M.
      tuberculosis, and highlights the interplay between mycolic acid synthesis, drug
      activation and mycobacterial virulence.

PMID- 19183277
TI  - Methylene tetrahydrofolate dehydrogenase/cyclohydrolase and the synthesis of 10
      CHO-THF are essential in Leishmania major.
AB  - 10-Formyl tetrahydrofolate (10-CHO-THF) is a key metabolite in C1 carbon
      metabolism, arising through the action of formate-tetrahydrofolate ligase (FTL)
      and/or 5,10-methenyltetrahydrofolate cyclohydrolase/5,10-methylene
      tetrahydrofolate dehydrogenase (DHCH). Leishmania major possesses single DHCH1
      and FTL genes encoding exclusively cytosolic proteins, unlike other organisms
      where isoforms occur in the mitochondrion as well. Recombinant DHCH1 showed
      typical NADP(+)-dependent methylene tetrahydrofolate DH and 5,10
      methenyltetrahydrofolate CH activities, and the DH activity was potently
      inhibited by a substrate analogue 5,10-CO-THF (K(i) 105 nM), as was Leishmania
      growth (EC(50) 1.1 microM). Previous studies showed null ftl(-) mutants were
      normal, raising the possibility that loss of the purine synthetic pathway had
      rendered 10-CHO-THF dispensable in evolution. We were unable to generate dhch1(-)
      null mutants by gene replacement, despite using a wide spectrum of nutritional
      supplements expected to bypass DHCH function. We applied an improved method for
      testing essential genes in Leishmania, based on segregational loss of episomal
      complementing genes rather than transfection; analysis of approximately 1400
      events without successful loss of DHCH1 again established its requirement.
      Lastly, we employed 'genetic metabolite complementation' using ectopically
      expressed FTL as an alternative source of 10-CHO-THF; now dhch1(-) null parasites
      were readily obtained. These data establish a requirement for 10-CHO-THF
      metabolism in L. major, and provide genetic and pharmacological validation of
      DHCH as a target for chemotherapy, in this and potentially other protozoan
      parasites.

PMID- 19183279
TI  - Structural insights into the molecular organization of the S-layer from
      Clostridium difficile.
AB  - Clostridium difficile expresses a surface layer (S-layer) which coats the surface
      of the bacterium and acts as an adhesin facilitating interaction of the bacterium
      with host enteric cells. The S-layer contains a high-molecular-weight S-layer
      protein (HMW SLP) and its low-molecular-weight partner protein (LMW SLP). We show
      that these proteins form a tightly associated non-covalent complex, the H/L
      complex, and we identify the regions of both proteins responsible for complex
      formation. The 2.4 A X-ray crystal structure of a truncated derivative of the LMW
      SLP reveals two domains. Domain 1 has a two-layer sandwich architecture while
      domain 2, predicted to orientate towards the external environment, contains a
      novel fold. Small-angle X-ray scattering analysis of the H/L complex shows an
      elongated molecule, with the two SLPs arranged 'end-to-end' interacting with each
      other through a small contact area. Alignment of LMW SLPs, which exhibit high
      sequence diversity, reveals a core of conserved residues that could reflect
      functional conservation, while allowing for immune evasion through sequence
      variation. These structures are the first described for the S-layer of a
      bacterial pathogen, and provide insights into the assembly and biogenesis of the
      S-layer.

PMID- 19183280
TI  - Microtubule-severing proteins are involved in flagellar length control and
      mitosis in Trypanosomatids.
AB  - Microtubules are key players in the biology of Trypanosomatid parasites, not only
      as classical components of the mitotic spindle, microtubule-organizing centres
      and flagellum but also as the essential constituent of the cytoskeleton. Their
      length dynamics are regulated by, among others, microtubule-severing proteins.
      Four and six genes encoding microtubule-severing proteins can be found
      bioinformatically in the Leishmania major and Trypanosoma brucei genome
      respectively. We investigated all these proteins in these organisms, which
      include the katanin, katanin-like, spastin and fidgetin, and looked at their
      subcellular localization as well as their putative function by examining 'loss-of
      function' phenotypes. The katanin-like KAT60b was found implicated in flagellar
      length reduction, but not in its size increase, while the katanin p80 subunit
      appeared clearly involved in cytokinesis. Fidgetin and spastin homologues were
      both localized in the nucleus: the first as a discrete and variable number of
      dots during most of the cell cycle, redistributing to the spindle and midbody
      during mitosis; the second concentrated as < or = 5 perinucleolar punctuations,
      similar to the electron-dense plaques identified in T. brucei, which were
      assimilated to kinetochores. This first study of microtubule-severing proteins in
      'divergent' eukaryotes gives further insight into the multiple functions of these
      proteins identified in the hitherto studied models.

PMID- 19183281
TI  - Cross-immunity and immune mimicry as mechanisms of resistance to the lantibiotic
      lacticin 3147.
AB  - Lantibiotics are antimicrobial peptides that possess great potential as clinical
      therapeutic agents. These peptides exhibit many beneficial traits and in many
      cases the emergence of resistance is extremely rare. In contrast, producers of
      lantibiotics synthesize dedicated immunity proteins to provide self-protection.
      These proteins have very specific activities and cross-immunity is rare. However,
      producers of two peptide lantibiotics, such as lacticin 3147, face the unusual
      challenge of exposure to two active peptides (alpha and beta). Here, in addition
      to establishing the contribution of LtnI and LtnFE to lacticin 3147 immunity,
      investigations were carried out to determine if production of a closely related
      lantibiotic (i.e. staphylococcin C55) or possession of LtnI/LtnFE homologues
      could provide protection. Here we establish that not only are staphylococcin C55
      producers cross-immune to lacticin 3147, and therefore represent a natural
      repository of Staphylococcus aureus strains that are protected against lacticin
      3147, but that functional immunity homologues are also produced by strains of
      Bacillus licheniformis and Enterococcus faecium. This result raises the spectre
      of resistance through immune mimicry, i.e. the emergence of lantibiotic-resistant
      strains from the environment resulting from the possession/acquisition of
      immunity gene homologues. These phenomena will have to be considered carefully
      when developing lantibiotics for clinical application.

PMID- 19183283
TI  - Atypical association of DDE transposition with conjugation specifies a new family
      of mobile elements.
AB  - We describe in Streptococcus agalactiae an atypical family of conjugative
      transposons named TnGBSs which associates DDE transposition and conjugation. We
      present evidence that the transposition of TnGBS2, the prototype of this family,
      is catalysed by a new class of DDE transposases that are widespread in Gram
      positive bacteria. Remarkably, transposition occurs in intergenic regions, 15 or
      16 bp upstream the -35 sequence of promoters, minimizing the burden on the host
      cell and suggesting an association between transcription and transposition.
      Transposition catalyses the formation of a circular intermediate that is
      substrate for subsequent conjugative intercellular transfer. Conjugation is
      initiated at an origin of transfer by a transposon-encoded relaxase. Whereas all
      integrative and conjugative elements described so far encode a phage-related
      integrase, TnGBS2 is the first example of conjugative transposon whose
      recombination is mediated by a DDE transposase. The combination of DDE
      transposition with conjugation implies recombination constraints linked to the
      physical separation of donor and recipient molecules.

PMID- 19183282
TI  - The archaeal RNA polymerase subunit P and the eukaryotic polymerase subunit Rpb12
      are interchangeable in vivo and in vitro.
AB  - The general subunit of all three eukaryotic RNA polymerases, Rpb12, and subunit P
      of the archaeal enzyme show sequence similarities in their N-terminal zinc ribbon
      and some highly conserved residues in the C-terminus. We report here that
      archaeal subunit P under the control of a strong yeast promoter could complement
      the lethal phenotype of a RPB12 deletion mutant and that subunit Rpb12 from yeast
      can functionally replace subunit P during reconstitution of the archaeal RNA
      polymerase. The DeltaP enzyme is unable to form stable open complexes, but can
      efficiently extend a dinucleotide on a premelted template or RNA on an elongation
      scaffold. This suggests that subunit P is directly or indirectly involved in
      promoter opening. The activity of the DeltaP enzyme can be rescued by the
      addition of Rpb12 or subunit P to transcription reactions. Mutation of cysteine
      residues in the zinc ribbon impair the activity of the enzyme in several assays
      and this mutated form of P is rapidly replaced by wild-type P in transcription
      reactions. The conserved zinc ribbon in the N-terminus seems to be important for
      proper interaction of the complete subunit with other RNA polymerase subunits and
      a 17-amino-acid C-terminal peptide is sufficient to support all basic RNA
      polymerase functions in vitro.

PMID- 19183284
TI  - Sodium-dependent dynamic assembly of membrane complexes in sodium-driven
      flagellar motors.
AB  - The bacterial flagellar motor is driven by the electrochemical potential of
      specific ions, H(+) or Na(+). The motor consists of a rotor and stator, and their
      interaction generates rotation. The stator, which is composed of PomA and PomB in
      the Na(+) motor of Vibrio alginolyticus, is thought to be a torque generator
      converting the energy of ion flux into mechanical power. We found that specific
      mutations in PomB, including D24N, F33C and S248F, which caused motility defects,
      affected the assembly of stator complexes into the polar flagellar motor using
      green fluorescent protein-fused stator proteins. D24 of PomB is the predicted
      Na(+)-binding site. Furthermore, we demonstrated that the coupling ion, Na(+), is
      required for stator assembly and that phenamil (an inhibitor of the Na(+)-driven
      motor) inhibited the assembly. Carbonyl cyanide m-chlorophenylhydrazone, which is
      a proton ionophore that collapses the sodium motive force in this organism at
      neutral pH, also inhibited the assembly. Thus we conclude that the process of
      Na(+) influx through the channel, including Na(+) binding, is essential for the
      assembly of the stator complex to the flagellar motor as well as for torque
      generation.

PMID- 19183286
TI  - Constitutive and herbivore-induced monoterpenes emitted by Populus x
      euroamericana leaves are key volatiles that orient Chrysomela populi beetles.
AB  - Chrysomela populi beetles feed on poplar leaves and extensively damage
      plantations. We investigated whether olfactory cues orientate landing and
      feeding. Young, unexpanded leaves of hybrid poplar emit constitutively a blend of
      monoterpenes, primarily (E)-beta-ocimene and linalool. This blend attracts
      inexperienced adults of C. populi that were not previously fed with poplar
      leaves. In mature leaves constitutively emitting isoprene, insect attack induces
      biosynthesis and emission of the same blend of monoterpenes, but in larger amount
      than in young leaves. The olfactometric test indicates that inexperienced beetles
      are more attracted by adult than by young attacked leaves, suggesting that
      attraction by induced monoterpenes is dose dependent. The blend does not attract
      adults that previously fed on poplar leaves. Insect-induced emission of
      monoterpenes peaks 4 d after the attack, and is also detected in non-attacked
      leaves. Induced monoterpene emission is associated in mature leaves with a larger
      decrease of isoprene emission. The reduction of isoprene emission is faster than
      photosynthesis reduction in attacked leaves, and also occurs in non-attacked
      leaves. Insect-induced monoterpenes are quickly and completely labelled by 13C.
      It is speculated that photosynthetic carbon preferentially allocated to
      constitutive isoprene in healthy leaves is in part diverted to induced
      monoterpenes after the insect attack.

PMID- 19183287
TI  - DNA binding of citrus dehydrin promoted by zinc ion.
AB  - Dehydrins are hydrophilic proteins that accumulate during embryogenesis and
      osmotic stress responses in plants. Here, we report an interaction between citrus
      dehydrin Citrus unshiu cold-regulated 15 kDa protein (CuCOR15) and DNA. Binding
      of CuCOR15 to DNA was detected by an electrophoretic mobility shift assay, a
      filter-binding assay and Southwestern blotting. The binding was stimulated by
      physiological concentrations of Zn2+, but little stimulation occurred when other
      divalent cations, such as Mg2+, Ca2+, Mn2+, Ni2+ and Cu2+, were substituted for
      Zn2+. Ethylenediaminetetraacetic acid cancelled the Zn2+-stimulated binding. A
      binding curve and competitor experiments suggested that the DNA binding of
      CuCOR15 exhibited low affinity and non-specificity. Moreover, tRNA competed with
      the DNA binding. Histidine-rich domains and a polylysine segment-containing
      domain participated in the DNA binding. These results suggest that CuCOR15 can
      interact with DNA, and also RNA, in the presence of Zn2+. Dehydrin may protect
      nucleic acids in plant cells during seed maturation and stress responses.

PMID- 19183285
TI  - Controlled degradation by ClpXP protease tunes the levels of the excision repair
      protein UvrA to the extent of DNA damage.
AB  - UV irradiation damages DNA and activates expression of genes encoding proteins
      helpful for survival under DNA stress. These proteins are often deleterious in
      the absence of DNA damage. Here, we investigate mechanisms used to regulate the
      levels of DNA-repair proteins during recovery by studying control of the
      nucleotide excision repair (NER) protein UvrA. We show that UvrA is induced after
      UV irradiation and reaches maximum levels between approximately 20 and 120 min
      post UV. During post-UV recovery, UvrA levels decrease principally as a result of
      ClpXP-dependent protein degradation. The rate of UvrA degradation depends on the
      amount of unrepaired pyrimidine dimers present; this degradation rate is
      initially slow shortly after UV, but increases as damage is repaired. This
      increase in UvrA degradation as repair progresses is also influenced by protein
      protein interactions. Genetic and in vitro experiments support the conclusion
      that UvrA-UvrB interactions antagonize degradation. In contrast, Mfd appears to
      act as an enhancer of UvrA turnover. Thus, our results reveal that a complex
      network of interactions contribute to tuning the level of UvrA in the cell in
      response to the extent of DNA damage and nicely mirror findings with excision
      repair proteins from eukaryotes, which are controlled by proteolysis in a similar
      manner.

PMID- 19183288
TI  - Isoprene synthesis protects transgenic tobacco plants from oxidative stress.
AB  - Isoprene emission represents a significant loss of carbon to those plant species
      that synthesize this highly volatile and reactive compound. As a tool for
      studying the role of isoprene in plant physiology and biochemistry, we developed
      transgenic tobacco plants capable of emitting isoprene in a similar manner to and
      at rates comparable to a naturally emitting species. Thermotolerance of
      photosynthesis against transient high-temperature episodes could only be observed
      in lines emitting high levels of isoprene; the effect was very mild and could
      only be identified over repetitive stress events. However, isoprene-emitting
      plants were highly resistant to ozone-induced oxidative damage compared with
      their non-emitting azygous controls. In ozone-treated plants, accumulation of
      toxic reactive oxygen species (ROS) was inhibited, and antioxidant levels were
      higher. Isoprene-emitting plants showed remarkably decreased foliar damage and
      higher rates of photosynthesis compared to non-emitting plants immediately
      following oxidative stress events. An inhibition of hydrogen peroxide
      accumulation in isoprene-emitting plants may stall the programmed cell death
      response which would otherwise lead to foliar necrosis. These results demonstrate
      that endogenously produced isoprene provides protection from oxidative damage.

PMID- 19183289
TI  - Increased abscisic acid levels in transgenic tobacco over-expressing 9 cis
      epoxycarotenoid dioxygenase influence H2O2 and NO production and antioxidant
      defences.
AB  - Abscisic acid (ABA) regulates the plant's adaptive responses to abiotic stresses.
      Over-expression of the 9-cis-epoxycarotenoid dioxygenase gene (SgNCED1) in the
      transgenic tobaccos increased ABA content and tolerance to drought and salt
      stresses. H2O2 and nitric oxide (NO) contents were enhanced in guard cells and
      mesophyll cells of the transgenic plants, accompanied with increased transcripts
      and activities of antioxidant enzymes including superoxide dismutase (SOD),
      catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR). The
      enhancements of H2O2 and NO and transcripts and activities of antioxidant enzymes
      in the transgenic plants were blocked by pre-treatments with inhibitor of ABA
      biosynthesis, scavengers of H2O2 and NO, and inhibitors of NADPH oxidase and NO
      synthase-like (NOS-like). The elevated production of NO in the transgenic plants
      was blocked by scavenger of H2O2 and inhibitors of NADPH oxidase, whereas H2O2
      level was not affected by scavenger of NO and inhibitor of NOS-like, indicating
      that H2O2 is essential for the elevated production of NO. The results demonstrate
      that the increased drought and salt tolerance in the transgenic plants is
      associated with ABA-induced production of H2O2 via NADPH oxidase and NO via NOS
      like, which sequentially induce transcripts and activities of SOD, CAT, APX and
      GR.

PMID- 19183290
TI  - Wound-induced apoplastic peroxidase activities: their roles in the production and
      detoxification of reactive oxygen species.
AB  - Production of reactive oxygen species (ROS) is a widely reported response of
      plants to wounding. However, the nature of enzymes responsible for ROS production
      and metabolism in the apoplast is still an open question. We identified and
      characterized the proteins responsible for the wound-induced production and
      detoxification of ROS in the apoplast of wheat roots (Triticum aestivum L.).
      Compared to intact roots, excised roots and leachates derived from them produced
      twice the amount of superoxide (O2(*-)). Wounding also induced extracellular
      peroxidase (ECPOX) activity mainly caused by the release of soluble peroxidases
      with molecular masses of 37, 40 and 136 kD. Peptide mass analysis by electrospray
      ionization-quadrupole time-of-flight-tandem mass spectrometry (ESI-QTOF-MS/MS)
      following lectin affinity chromatography of leachates showed the presence of
      peroxidases in unbound (37 kD) and bound (40 kD) fractions. High sensitivity of
      O2(*-)-producing activity to peroxidase inhibitors and production of O2(*-) by
      purified peroxidases in vitro provided evidence for the involvement of ECPOXs in
      O2(*-) production in the apoplast. Our results present new insights into the
      rapid response of roots to wounding. An important component of this response is
      mediated by peroxidases that are released from the cell surface into the apoplast
      where they can display both oxidative and peroxidative activities.

PMID- 19183291
TI  - Herbivory-induced signalling in plants: perception and action.
AB  - Plants and herbivores have been interacting for millions of years. Over time,
      plants have evolved mechanisms to defend against herbivore attacks. Herbivore
      challenged plants reconfigure their metabolism to produce compounds that are
      toxic, repellant or anti-digestive for the herbivores. Some compounds are
      volatile signals that attract the predators of herbivores. All these responses
      are tightly regulated by a signalling network triggered by the plant's perception
      machinery. Several compounds that specifically elicit herbivory-induced responses
      in plants have been isolated from herbivore oral secretions and oviposition
      fluids. Elicitor perception is rapidly followed by cell membrane depolarization,
      calcium influx and mitogen-activated protein kinase (MAPK) activation; plants
      also elevate the concentrations of reactive oxygen and nitrogen species, and
      modulate phytohormone levels accordingly. In addition to these reactions in the
      herbivore-attacked regions of a leaf, defence responses are also mounted in
      unattacked parts of the attacked leaf and as well in unattacked leaves. In this
      review, we summarize recent progress in understanding how plants recognize
      herbivory, the involvement of several important signalling pathways that mediate
      the responses to herbivore attack and the signals that transduce local into
      systemic responses.

PMID- 19183292
TI  - Puccinellia tenuiflora maintains a low Na+ level under salinity by limiting
      unidirectional Na+ influx resulting in a high selectivity for K+ over Na+.
AB  - Puccinellia tenuiflora is a useful monocotyledonous halophyte that might be used
      for improving salt tolerance of cereals. This current work has shown that P.
      tenuiflora has stronger selectivity for K+ over Na+ allowing it to maintain
      significantly lower tissue Na+ and higher K+ concentration than that of wheat
      under short- or long-term NaCl treatments. To assess the relative contribution of
      Na+ efflux and influx to net Na+ accumulation, unidirectional 22Na+ fluxes in
      roots were carried out. It was firstly found that unidirectional 22Na+ influx
      into root of P. tenuiflora was significantly lower (by 31-37%) than in wheat
      under 100 and 150 mM NaCl. P. tenuiflora had lower unidirectional Na+ efflux than
      wheat; the ratio of efflux to influx was similar between the two species. Leaf
      secretion of P. tenuiflora was also estimated, and found the loss of Na+ content
      from leaves to account for only 0.0006% of the whole plant Na+ content over 33 d
      of NaCl treatments. Therefore, it is proposed that neither unidirectional Na+
      efflux of roots nor salt secretion by leaves, but restricting unidirectional Na+
      influx into roots with a strong selectivity for K+ over Na+ seems likely to
      contribute to the salt tolerance of P. tenuiflora.

PMID- 19183293
TI  - Functional anatomy controls ion distribution in banana leaves: significance of
      Na+ seclusion at the leaf margins.
AB  - Typical salt stress symptoms appear in banana (Musa sp., cv. 'Grand Nain' AAA)
      only along the leaf margins. Mineral analysis of the dry matter of plants treated
      with increasing concentrations of KCl or NaCl revealed significant accumulation
      of Na+, but not of K+ or Cl(-), in the affected leaf margins. The differential
      distribution of the three ions suggests that water and ion movement out of the
      xylem is mostly symplastic and, in contrast to K+ and Cl(-), there exists
      considerable resistance to the flow of Na+ from the xylem to the adjacent
      mesophyll and epidermis. The parallel veins of the lamina are enclosed by several
      layers of bundle sheath parenchyma; in contrast, the large vascular bundle that
      encircles the entire lamina, and into which the parallel veins merge, lacks a
      complete bundle sheath. Xylem sap containing a high concentration of Na+ is
      'pulled' by water tension from the marginal vein back into the adjacent mesophyll
      without having to cross a layer of parenchyma tissue. When the marginal vein was
      dissected from the lamina, the pattern of Na+ distribution in the margins changed
      markedly. The distinct anatomy of the marginal vein plays a major role in the
      accumulation of Na+ in the margins, with the latter serving as a 'dumping site'
      for toxic molecules.

PMID- 19183294
TI  - Environmental perception avenues: the interaction of cytokinin and environmental
      response pathways.
AB  - Cytokinins were discovered in the 1950s by their ability to promote cell division
      in cultured plant cells. Recently, there have been significant breakthroughs in
      our understanding of the biosynthesis, metabolism, perception and signal
      transduction of this phytohormone. These advances, coupled with physiological and
      other approaches, have enabled remarkable progress to be made in our
      understanding of the interactions between cytokinin function and environmental
      inputs. In this review, we first highlight the most recent advances in our
      understanding of cytokinin biosynthesis, metabolism and signalling. We then
      discuss how various environmental signals interact with these pathways to
      modulate plant growth, development and physiology.

PMID- 19183295
TI  - Cortical microtubule as a sensor and target of nitric oxide signal during the
      defence responses to Verticillium dahliae toxins in Arabidopsis.
AB  - The molecular mechanisms of signal transduction of plants in response to
      Verticillium dahliae (VD) are not known. Here, we show that Arabidopsis reacts to
      VD-toxins with a rapid burst of nitric oxide (NO) and cortical microtubule
      destabilization. VD-toxins treatment triggered a disruption of cortical
      microtubules network. This disruption can be influenced by NO production.
      However, cortical microtubule disruptions were not involved in regulating the NO
      production. The results indicated that NO may act as an upstream signalling
      molecule to trigger the depolymerization of cortical microtubule. Cortical
      microtubules may act as a target of NO signal and as a sensor to mediate the
      activation of PR-1 gene expression. These results suggested that NO production
      and cortical microtubule dynamics appeared to be parts of the important
      signalling system and are involved in the defence mechanisms to VD-toxins in
      Arabidopsis.

PMID- 19183296
TI  - Plasma membrane H-ATPase-dependent citrate exudation from cluster roots of
      phosphate-deficient white lupin.
AB  - White lupin (Lupinus albus L.) is able to grow on soils with sparingly available
      phosphate (P) by producing specialized structures called cluster roots. To
      mobilize sparingly soluble P forms in soils, cluster roots release substantial
      amounts of carboxylates and concomitantly acidify the rhizosphere. The
      relationship between acidification and carboxylate exudation is still largely
      unknown. In the present work, we studied the linkage between organic acids
      (malate and citrate) and proton exudations in cluster roots of P-deficient white
      lupin. After the illumination started, citrate exudation increased transiently
      and reached a maximum after 5 h. This effect was accompanied by a strong
      acidification of the external medium and alkalinization of the cytosol, as
      evidenced by in vivo nuclear magnetic resonance (NMR) analysis. Fusicoccin, an
      activator of the plasma membrane (PM) H+-ATPase, stimulated citrate exudation,
      whereas vanadate, an inhibitor of the H+-ATPase, reduced citrate exudation. The
      burst of citrate exudation was associated with an increase in expression of the
      LHA1 PM H+-ATPase gene, an increased amount of H+-ATPase protein, a shift in pH
      optimum of the enzyme and post-translational modification of an H+-ATPase protein
      involving binding of activating 14-3-3 protein. Taken together, our results
      indicate a close link in cluster roots of P-deficient white lupin between the
      burst of citrate exudation and PM H+-ATPase-catalysed proton efflux.

PMID- 19183297
TI  - Rubisco content and photosynthesis of leaves at different positions in transgenic
      rice with an overexpression of RBCS.
AB  - As ribulose 1.5-bisphosphate carboxylase/oxygenase (Rubisco) activity limits
      light-saturated photosynthesis under present atmospheric condition, the effects
      of an overexpression of RBCSon Rubisco content and photosynthesis were examined
      in the leaves at different positions in rice (Oryza sativa L.). Rubisco content
      in the transformant was significantly greater in the uppermost, fully expanded
      leaves but decreased to levels similar to those in wild-type plants in the lower
      leaves. The mRNA levels of total RBCS and rbcL in these leaves were much less
      than those in the expanding leaves, where Rubisco synthesis is active, suggesting
      commensurately low level of synthesis. Although the activation state of Rubisco
      was lower in the uppermost, fully expanded leaves of the transformant, it
      recovered to its full level in the lower leaves. As a result, the photosynthetic
      rate did not differ in leaves at the same position between the transformant and
      the wild type. Similarly, whole plant biomass did not differ between these
      genotypes. Thus, we conclude that although the overexpression of RBCS led to an
      enhancement of Rubisco protein content in the uppermost, fully expanded leaves,
      it does not result in increased photosynthetic rates or plant biomass, because of
      an apparent down-regulation in its activation state.

PMID- 19183298
TI  - A modular concept of plant foraging behaviour: the interplay between local
      responses and systemic control.
AB  - In this paper we examined the notion that plant foraging for resources in
      heterogeneous environments must involve: (1) plasticity at the level of
      individual modules in reaction to localized environmental signals; and (2) the
      potential for modification of these responses either by the signals received from
      connected modules that may be exposed to different conditions, or by the signals
      reflecting the overall resource status of the plant. A conceptual model is
      presented to illustrate how plant foraging behaviour is achieved through these
      processes acting in concert, from the signal reception through signal
      transduction to morphological or physiological response. Evidence to support the
      concept is reviewed, using selective root placement under nutritionally
      heterogeneous conditions and elongation responses of stems and petioles to shade
      as examples. We discussed how the adoption of this model can promote
      understanding of the ecological significance of foraging behaviour. We also
      identified a need to widen the experimental repertoires of both molecular
      physiology and ecology in order to increase our insight into both the regulation
      and functioning of foraging responses, and their relationship with the patterns
      of environmental heterogeneity under which plants have evolved.

PMID- 19183299
TI  - Over-expression of OsIRT1 leads to increased iron and zinc accumulations in rice.
AB  - Uptake and translocation of micronutrients are essential for plant growth. These
      micronutrients are also important food components. We generated transgenic rice
      plants over-expressing OsIRT1 to evaluate its functional roles in metal
      homeostasis. Those plants showed enhanced tolerance to iron deficiency at the
      seedling stage. In paddy fields, this over-expression caused plant architecture
      to be altered. In addition, those plants were sensitive to excess Zn and Cd,
      indicating that OsIRT1 also transports those metals. As expected, iron and zinc
      contents were elevated in the shoots, roots and mature seeds of over-expressing
      plants. This demonstrates that OsIRT1 can be used for enhancing micronutrient
      levels in rice grains.

PMID- 19183300
TI  - Using combined measurements of gas exchange and chlorophyll fluorescence to
      estimate parameters of a biochemical C photosynthesis model: a critical appraisal
      and a new integrated approach applied to leaves in a wheat (Triticum aestivum)
      canopy.
AB  - We appraised the literature and described an approach to estimate the parameters
      of the Farquhar, von Caemmerer and Berry model using measured CO(2) assimilation
      rate (A) and photosystem II (PSII) electron transport efficiency (Phi(2)). The
      approach uses curve fitting to data of A and Phi(2) at various levels of incident
      irradiance (I(inc)), intercellular CO(2) (C(i)) and O(2). Estimated parameters
      include day respiration (R(d)), conversion efficiency of I(inc) into linear
      electron transport of PSII under limiting light [kappa(2(LL))], electron
      transport capacity (J(max)), curvature factor (theta) for the non-rectangular
      hyperbolic response of electron flux to I(inc), ribulose 1.5-bisphosphate
      carboxylase/oxygenase (Rubisco) CO(2)/O(2) specificity (S(c/o)), Rubisco
      carboxylation capacity (V(cmax)), rate of triose phosphate utilization (T(p)) and
      mesophyll conductance (g(m)). The method is used to analyse combined gas exchange
      and chlorophyll fluorescence measurements on leaves of various ages and positions
      in wheat plants grown at two nitrogen levels. Estimated S(c/o) (25 degrees C) was
      3.13 mbar microbar(-1); R(d) was lower than respiration in the dark; J(max) was
      lower and theta was higher at 2% than at 21% O(2); kappa(2(LL)), V(cmax), J(max)
      and T(p) correlated to leaf nitrogen content; and g(m) decreased with increasing
      C(i) and with decreasing I(inc). Based on the parameter estimates, we surmised
      that there was some alternative electron transport.

PMID- 19183301
TI  - Systems biology of growth factor-induced receptor endocytosis.
AB  - Clathrin-mediated endocytosis sorts for degradation of more than 50 different
      growth factor receptors capable of relaying growth and differentiation signals by
      means of their cytoplasm-facing, intrinsic tyrosine kinase activity. The kinetics
      and alternative routings of receptor endocytosis critically regulate growth
      factor signaling, which underscores the importance of understanding mechanisms
      underlying fail-safe operation (robustness) and fidelity of the pathway. Like
      other robust systems, a layered hub-centric network controls receptor
      endocytosis. Characteristically, the modular hubs (e.g., AP2-Eps15 and Hrs)
      contain a membrane-anchoring lipid-binding domain, an ubiquitin-binding module,
      which recruits ubiquitinylated cargo, and a machinery enabling homo-assembly.
      Scheduled hub transitions, as well as cascades of Rab family guanosine
      triphosphatases and membrane bending machineries, define points of commitment to
      vesicle budding, thereby securing unidirectional trafficking. System's
      bistability permits stimulation by a growth factor, which oscillates a series of
      switches based on posttranslational protein modifications (i.e., phosphorylation,
      ubiquitinylation and neddylation), as well as transient low-affinity/high-avidity
      protein assemblies. Cbl family ubiquitin ligases, along with a set of
      phosphotyrosine-binding adaptors (e.g., Grb2), integrate receptor endocytosis
      into the densely wired networks of signal transduction pathways, which are
      involved in health and disease.

PMID- 19183302
TI  - Intraphagosomal measurement of the magnitude and duration of the oxidative burst.
AB  - Generation of an oxidative burst within the phagosomes of neutrophils, dendritic
      cells and macrophages is an essential component of the innate immune system. To
      examine the kinetics of the oxidative burst in the macrophage phagosome, we
      developed two new assays using beads coated with oxidation-sensitive
      fluorochromes.These assays permitted quantification and temporal resolution of
      the oxidative burst within the phagosome. The macrophage phagosomal oxidative
      burst is short lived,with oxidation of bead-associated substrates reaching
      maximal activity within 30 min following phagocytosis.Additionally, the extent
      and rate of macrophage phagosomal substrate oxidation were subject to
      immunomodulation by activation with lipopolysaccharide and/or interferon-gamma.

PMID- 19183303
TI  - Peroxisomal targeting of PTS2 pre-import complexes in the yeast Saccharomyces
      cerevisiae.
AB  - Posttranslational matrix protein import into peroxisomes uses either one of the
      two peroxisomal targeting signals (PTS), PTS1 and PTS2. Unlike the PTS1 receptor
      Pex5p, the PTS2 receptor Pex7p is necessary but not sufficient to target cargo
      proteins into the peroxisomal matrix and requires coreceptors. Saccharomyces
      cerevisiae possesses two coreceptors, Pex18p and Pex21p, with a redundant but not
      a clearly defined function. To gain further insight into the early events of this
      import pathway, PTS2 pre-import complexes of S. cerevisiae were isolated and
      characterized by determination of size and protein composition in wild-type and
      different mutant strains. Mass spectrometric analysis of the cytosolic PTS2 pre
      import complex indicates that Fox3p is the only abundant PTS2 protein under
      oleate growth conditions. Our data strongly suggest that the formation of the
      ternary cytosolic PTS2 pre-import complex occurs hierarchically. First, Pex7p
      recognizes cargo proteins through its PTS2 in the cytosol. In a second step, the
      coreceptor binds to this complex, and finally, this ternary 150 kDa pre-import
      complex docks at the peroxisomal membrane, where both the PTS1 and the PTS2
      import pathways converge. Gel filtration analysis of membrane-bound subcomplexes
      suggests that Pex13p provides the initial binding partner at the peroxisomal
      membrane, whereas Pex14p assembles with Pex18p in high-molecular-weight complexes
      after or during dissociation of the PTS2 receptor.

PMID- 19183304
TI  - The Hyperglycemia and Adverse Pregnancy Outcomes trial: answers but still more
      questions about the management of gestational diabetes.

PMID- 19183305
TI  - Addressing insulin resistance in Type 1 diabetes.
AB  - Type 1 diabetes is recognised to include an element of insulin resistance.
      Insulin resistance is an independent risk factor for the development of macro-
      and microvascular complications of Type 1 diabetes and may also contribute to the
      development of the disease. This understanding comes at a time when the incidence
      of Type 1 diabetes appears to be rising and the public health burden from its
      vascular complications is high. A variety of safe and efficacious manoeuvres are
      available to redress insulin resistance in Type 2 diabetes. So far however,
      clinical trials addressing insulin resistance in Type 1 diabetes have been small
      with only short periods of follow-up. Regardless, these trials have yielded
      promising results. This review examines the evidence for insulin resistance in
      the pathophysiology of Type 1 diabetes and its complications, the problems
      associated with its measurement, and summarizes the trials aimed at reducing
      insulin resistance in Type 1 diabetes. This includes a meta-analysis of
      controlled trials of adjuvant metformin in Type 1 diabetes.

PMID- 19183306
TI  - NICE guidance on diabetes in pregnancy: management of diabetes and its
      complications from preconception to the postnatal period. NICE clinical guideline
      63. London, March 2008.
AB  - The care of pregnant women with disorders of glucose metabolism is a satisfying
      part of diabetes care but outcomes remain less than ideal. The evidence base to
      improve care has grown over subsequent decades and clinicians will welcome up-to
      date NICE guidance on this topic. This review looks at the guidance from the
      perspective of a secondary care diabetes team.

PMID- 19183307
TI  - Commentary from Copenhagen on the NICE guideline on management of diabetes and
      its complications from preconception to the postnatal period.

PMID- 19183308
TI  - Effects of fat supplementation on glycaemic response and gastric emptying in
      adolescents with Type 1 diabetes.
AB  - AIMS: To compare the glycaemic response to meals with different fat content in
      adolescents with Type 1 diabetes mellitus (T1DM) and to investigate associations
      with gastric emptying. METHODS: In this randomized, cross-over study, paired
      results were obtained from seven adolescents with T1DM who ingested on different
      days two meals with the same carbohydrate and protein content, but different fat
      and energy content (2 and 38 g fat, 320 and 640 kcal, respectively). Paracetamol
      was mixed into the meals and gastric emptying was estimated by the paracetamol
      absorption method. All subjects were normoglycaemic and given 7 IU insulin aspart
      at commencement of ingestion. Postprandial blood samples were taken during 4 h.
      RESULTS: The areas under the curves for plasma glucose and serum paracetamol
      concentrations were larger after the low-fat than after the high-fat meal during
      the first 2 h (P = 0.047 and P = 0.041, respectively). The difference between
      meals in time-to-peak in glucose and paracetamol concentrations did not reach
      statistical significance (high-fat vs. low-fat meal: 210 min (120-240) vs. 120
      min (50-240), P = 0.080 and 120 min (75-180) vs. 60 min (60-120), P = 0.051,
      respectively). Changes in glucose concentrations correlated with simultaneous
      changes in paracetamol concentrations (P < 0.001). CONCLUSIONS: For the first
      time, we have shown that the initial glycaemic response is reduced after a meal
      with higher compared with a meal with lower fat content in adolescents with T1DM
      given a rapid-acting insulin analogue preprandially. The type and dose of
      preprandial insulin may need adjustment to the fat content of the meal to reach
      postprandial normoglycaemia.

PMID- 19183309
TI  - Combined association of maternal and paternal family history of diabetes with
      plasma leptin and adiponectin in overweight Hispanic children.
AB  - AIMS: To investigate the importance of a maternal and paternal family history of
      Type 2 diabetes and their combined association with plasma leptin and adiponectin
      levels in overweight Latino children with a family history of Type 2 diabetes
      (T2DM). METHODS: This cross-sectional study investigated the combined association
      of a maternal and paternal family history of T2DM with leptin and adiponectin in
      175 overweight Latino children (age 11.1 +/- 1.7 years). All subjects had a
      family history of T2DM. Plasma adiponectin and leptin levels, body fat measured
      by dual-energy X-ray absorptiometry, Tanner stage, age and insulin sensitivity
      were assessed. RESULTS: After adjustment for age, gestational diabetes, insulin
      sensitivity and body fat, a combined maternal and paternal family history of T2DM
      was associated with higher leptin concentrations (P = 0.004) compared with a
      maternal or paternal family history alone. This association was most pronounced
      at Tanner stage 1 (P for interaction family history x tanner stage = 0.022). The
      presence of a combined maternal and paternal family history of T2DM accounted for
      4% (P = 0.003) of the variation in leptin concentrations. No such combined
      association was observed for adiponectin levels. CONCLUSIONS: Maternal and
      paternal family history of T2DM may have an additive impact on leptin, but not on
      adiponectin levels independent of adiposity and insulin sensitivity in overweight
      Latino children. This may contribute to a further clinically relevant
      deterioration of metabolic health in this population.

PMID- 19183310
TI  - Childhood body mass index (BMI), breastfeeding and risk of Type 1 diabetes:
      findings from a longitudinal national birth cohort.
AB  - AIMS: To perform a longitudinal analysis of the association between childhood
      body mass index (BMI) and later risk of Type 1 diabetes, controlling for socio
      economic status, birthweight, height in early and late childhood, breastfeeding
      history and pubertal status. METHODS: Analysis of the 1970 British Birth Cohort,
      followed up at age 5, 10 and 30 years (n = 11,261). Data were available on
      birthweight, breastfeeding; height, weight, pubertal status, socio-economic
      status at age 10 years; self-report data on history of diabetes (type, age at
      onset) at age 30 years. Cox proportional hazards models were used to examine
      relations of childhood growth, socio-economic status and breastfeeding history to
      the incidence of Type 1 diabetes between 10 and 30 years of age. RESULTS: Sixty
      one subjects (0.5%) reported Type 1 diabetes at 30 years of age; 47 (77%)
      reported onset >or= age 10 years. Higher BMI z-score at 10 years predicted higher
      risk of subsequent Type 1 diabetes (hazard ratio 1.8, 95% confidence interval 1.2
      to 2.8, P = 0.01) when adjusted for birthweight, pubertal status, breastfeeding
      history and socio-economic status. Repeating the model for childhood obesity, the
      hazard ratio was 3.1 (1.0, 9.3; P = 0.05). Birthweight, breastfeeding, height
      growth and pubertal timing were not associated with incidence of Type 1 diabetes.
      CONCLUSIONS: Higher BMI in childhood independently increased the risk of later
      Type 1 diabetes, supporting suggestions that obesity may provide a link between
      Type 1 and Type 2 diabetes. This supports observations of a rise in Type 1
      diabetes prevalence. Reduction in childhood obesity may reduce the incidence of
      Type 1 as well as Type 2 diabetes.

PMID- 19183311
TI  - Prevalence and projections of diabetes and pre-diabetes in adults in Sri Lanka-
      Sri Lanka Diabetes, Cardiovascular Study (SLDCS).
AB  - AIMS: To determine the prevalence of diabetes mellitus and pre-diabetes (impaired
      fasting glucose and impaired glucose tolerance) in adults in Sri Lanka.
      Projections for the year 2030 and factors associated with diabetes and pre
      diabetes are also presented. METHODS: This cross-sectional study was conducted
      between 2005 and 2006. A nationally representative sample of 5000 adults aged
      >or= 18 years was selected by a multi-stage random cluster sampling technique.
      Fasting plasma glucose was tested in all participants and a 75-g oral glucose
      tolerance test was performed in non-diabetic subjects. Prevalence was estimated
      for those > 20 years of age. RESULTS: Response rate was 91% (n = 4532), males
      40%, age 46.1 +/- 15.1 years (mean +/- standard deviation). The age-sex
      standardized prevalence (95% confidence interval) of diabetes for Sri Lankans
      aged >or= 20 years was 10.3% (9.4-11.2%) [males 9.8% (8.4-11.2%), females 10.9%
      (9.7-12.1%), P = 0.129). Thirty-six per cent (31.9-40.1%) of all diabetic
      subjects were previously undiagnosed. Diabetes prevalence was higher in the urban
      population compared with rural [16.4% (13.8-19.0%) vs. 8.7% (7.8-9.6%); P <
      0.001]. The prevalence of overall, urban and rural pre-diabetes was 11.5% (10.5
      12.5%), 13.6% (11.2-16.0%) and 11.0% (10.0-12.0%), respectively. Overall, 21.8%
      (20.5-23.1%) had some form of dysglycaemia. The projected diabetes prevalence for
      the year 2030 is 13.9%. Those with diabetes and pre-diabetes compared with normal
      glucose tolerance were older, physically inactive, frequently lived in urban
      areas and had a family history of diabetes. They had higher body mass index,
      waist circumference, waist-hip ratio, systolic/diastolic blood pressure, low
      density lipoprotein cholesterol and triglycerides. Insulin was prescribed to 4.4%
      (2.7-6.1%) of all diabetic subjects. CONCLUSIONS: One in five adults in Sri Lanka
      has either diabetes or pre-diabetes and one-third of those with diabetes are
      undiagnosed.

PMID- 19183312
TI  - Point-of-care testing as a tool for screening for diabetes and pre-diabetes.
AB  - AIM: To determine the utility of finger-prick point-of-care testing (POCT) of
      blood glucose for the detection of dysglycaemia. METHODS: A fasting POCT and an
      oral glucose tolerance test (OGTT) with laboratory assays were performed as part
      of the baseline screening for 5309 participants enrolled in the Te Wai o Rona
      Diabetes Prevention Strategy. Participants were aged 46 +/- 19 years with no self
      reported diabetes. Dysglycaemia, including diabetes, was defined using World
      Health Organization criteria. Agreement between the two fasting plasma glucose
      measurements and their screening properties (with sensitivity and specificity for
      cut points) were compared using receiver operator characteristic analysis.
      RESULTS: A total of 3225 participants had both capillary and venous fasting blood
      sampled within 30 min and then underwent OGTT. New diabetes was found in 161
      participants (5.0%) and pre-diabetes in 414 [impaired glucose tolerance 299
      (9.3%), impaired fasting glucose 115 (3.6%)]. The mean difference in capillary
      and venous measures was 0.02 mmol/l (95% confidence interval -0.04 to +0.01;
      limits of agreement -1.37 to 1.33 mmol/l). Capillary POCT was a poorer predictor
      of dysglycaemia and impaired glucose tolerance and new diabetes (area under curve
      0.76 and 0.71) than venous laboratory analysis (area under curve 0.87 and 0.81
      respectively). Optimal screening criteria were best at a venous glucose of 5.4
      mmol/l; 77% sensitivity/specificity. CONCLUSIONS: POCT significantly
      underestimated the true blood glucose at diagnostic levels for diabetes. POCT
      cannot be recommended as a means of screening for or diagnosing diabetes or pre
      diabetes.

PMID- 19183313
TI  - Treatment of chronic diabetic foot ulcers with bemiparin: a randomized, triple
      blind, placebo-controlled, clinical trial.
AB  - AIMS: To assess the efficacy and safety of bemiparin in the treatment of chronic
      diabetic foot ulcers. METHODS: A triple-blind, parallel, randomized, placebo
      controlled trial. Patients aged > 18 years, [corrected] with diabetes for at
      least 3 years, and with a foot ulcer persisting for > 3 months were selected from
      39 Spanish centres. Bemiparin 3500 IU/day for 10 days, followed by 2500 IU/day
      for up to 3 months plus standard care for ulcers, was compared with placebo plus
      standard care for ulcers for 3 months. The primary efficacy end-point was ulcer
      improvement, defined as an objective decrease in ulcer area of >or= 50%, measured
      by digital photography and ImageJ software, and/or any decrease in Wagner's ulcer
      grade at 3 months. RESULTS: Ulcer improvement rates were 70.3% (26 of 37
      patients) in the bemiparin group and 45.5% (15 of 33 patients) in the placebo
      group [absolute difference 24.8; 95% confidence interval (CI) 2.3, 47.3; P =
      0.035] (number needed to treat 4; 95% CI 2, 43). Complete healing rates at 3
      months were similar in both groups (35.1% vs. 33.3%; P = 0.874), as were the
      number of adverse events. CONCLUSIONS: Bemiparin is more effective than placebo
      in the management of diabetic foot ulcers and has few side-effects.

PMID- 19183314
TI  - A longitudinal study of affective and anxiety disorders, depressive affect and
      diabetes distress in adults with Type 2 diabetes.
AB  - AIMS: To report the prevalence and correlates of affective and anxiety disorders,
      depressive affect and diabetes distress over time. METHODS: In a non
      interventional study, 506 patients with Type 2 diabetes were assessed three times
      over 18 months (9-month intervals) for: major depressive disorder (MDD), general
      anxiety disorder (GAD), panic disorder (PANIC), dysthymia (DYS) (Composite
      International Diagnostic Interview); depressive affect [Center for
      Epidemiological Studies-Depression (CES-D)]; Diabetes Distress Scale (DDS);
      HbA(1c); and demographic data. RESULTS: Diabetic patients displayed high rates of
      affective and anxiety disorders over time, relative to community adults: 60%
      higher for MDD, 123% for GAD, 85% for PANIC, 7% for DYS. The prevalence of
      depressive affect and distress was 60-737% higher than of affective and anxiety
      disorders. The prevalence of individual patients with an affective and anxiety
      disorder over 18 months was double the rate assessed at any single wave. The
      increase for CES-D and DDS was about 60%. Persistence of CES-D and DDS disorders
      over time was significantly greater than persistence of affective and anxiety
      disorders, which tended to be episodic. Younger age, female gender and high
      comorbidities were related to persistence of all conditions over time. HbA(1c)
      was positively related to CES-D and DDS, but not to affective and anxiety
      disorders over time. CONCLUSIONS: The high prevalence of comorbid disorders and
      the persistence of depressive affect and diabetes distress over time highlight
      the need for both repeated mental health and diabetes distress screening at each
      patient contact, not just periodically, particularly for younger adults, women
      and those with complications/comorbidities.

PMID- 19183316
TI  - Prevalence and reasons for insulin refusal in Bangladeshi patients with poorly
      controlled Type 2 diabetes in East London.
AB  - AIMS: To determine the prevalence and reasons for refusal to commence insulin in
      Bangladeshi patients with Type 2 diabetes. METHODS: A survey of 212 Bangladeshi
      patients seen in a hospital diabetes unit, with poor glycaemic control
      (HbA(1c)>or= 8.0%) on maximum oral glucose-lowering therapy, in whom insulin was
      deemed necessary. Patients who refused insulin were invited to attend focus
      groups. Data were analysed by thematic content analysis using the constant
      comparative method. RESULTS: Of 212 patients offered insulin, 122 (57.5%)
      commenced insulin immediately, 47 (22.1%) started insulin within 6 months and 43
      (20.3%) refused to commence insulin despite repeated counselling. Thirty-six
      (83.7%) of those who refused insulin agreed to participate in focus groups.
      Reasons for insulin refusal included: disease severity--perceptions that
      requirement for insulin was an indicator of a more serious stage of their
      condition; insulin leading to premature death--common suggestion that commencing
      insulin led to early death; loss of control--including fear of hypoglycaemia,
      weight gain, loss of independence and reliance on others to give insulin or look
      for signs of hypoglycaemia; lack of perception of benefits--poor perception of
      the benefits of improved glycaemic control on quality of life and cardiovascular
      risk; needle anxiety--a significant proportion of subjects conveyed concern over
      frequent injections. CONCLUSIONS: Insulin refusal is common in Bangladeshi
      subjects with Type 2 diabetes and poor glycaemic control. A number of factors
      contribute to this, and methods to overcome the barriers to insulin therapy need
      to be sought.

PMID- 19183315
TI  - Symptoms of depression prospectively predict poorer self-care in patients with
      Type 2 diabetes.
AB  - AIMS: To examine prospectively the association of depression symptoms with
      subsequent self-care and medication adherence in patients with Type 2 diabetes
      mellitus. METHODS: Two hundred and eight primary care patients with Type 2
      diabetes completed the Harvard Department of Psychiatry/National Depression
      Screening Day Scale (HANDS) and the Summary of Diabetes Self-Care Activities
      (SDSCA) at baseline and at follow-up, an average of 9 months later. They also
      self-reported medication adherence at baseline and at a follow-up. RESULTS:
      Baseline HANDS scores ranged from 0 to 27, with a mean score of 5.15 +/- 4.99. In
      separate linear regression models that adjusted for baseline self-care, patients
      with higher levels of depressive symptoms at baseline reported significantly
      lower adherence to general diet recommendations and specific recommendations for
      consumption of fruits and vegetables and spacing of carbohydrates; less exercise;
      and poorer foot care at follow-up (beta ranging from -0.12 to -0.23; P < 0.05).
      Similarly, each one-point increase in baseline HANDS score was associated with a
      1.08-fold increase in the odds of non-adherence to prescribed medication at
      follow-up (95% confidence interval 1.001, 1.158, P = 0.047). Increases in
      depression scores over time also predicted poorer adherence to aspects of diet
      and exercise. CONCLUSIONS: Depressive symptoms predict subsequent non-adherence
      to important aspects of self-care in patients with Type 2 diabetes, even after
      controlling for baseline self-care. Although the relationship between symptoms of
      depression and poorer diabetes self-care is consistent, it is not large, and
      interventions may need to address depression and self-care skills simultaneously
      in order to maximize effects on diabetes outcomes.

PMID- 19183317
TI  - Twice-daily variable insulin regimens: proportions of insulin types have little
      impact on glycaemic control in primary school-aged children.
AB  - AIM: To ascertain the relationship between glycaemic outcome and proportions and
      timing of insulin admixture in a cohort of primary school-aged children who were
      receiving insulin in a twice-daily regimen. METHODS: Children aged 4-10 years
      with Type 1 diabetes of > 2 years duration and on twice-daily variable insulin
      regimens were eligible for inclusion in this study, which took place over a 12
      month period. Characteristics of insulin regimen [total daily dose (TDD),
      proportion of total daily dose given in the morning and proportion of the TDD
      given as intermediate-acting insulin] were compared with parameters of glycaemia
      including glycated haemoglobin (HbA(1c)) and continuous glucose monitoring
      measures (mean glucose, per cent time in various glycaemic ranges, and intra- and
      inter-day glycaemic variation). RESULTS: Forty-nine children completed the study.
      Participants were all prepubertal at the start of the study and representative of
      the local diabetes population aged 4-10 years (mean age 8.2 years, mean duration
      of diabetes 3.5 years, mean HbA(1c) 8.1%). The mean TDD was 0.9 units/kg/day
      (range 0.6-1.3). The TDD, percentage of TDD given as intermediate-acting insulin
      and the percentage of TDD given as the morning dose were not associated with
      HbA(1c), mean continuous glucose monitoring system glucose, per cent time in
      various glycaemic ranges or intra- and inter-day glycaemic variation.
      CONCLUSIONS: Insulin proportions in twice-daily, variable insulin regimens are
      not associated with any short- or medium-term glycaemic outcomes.

PMID- 19183318
TI  - 'Educator talk' and patient change: some insights from the DESMOND (Diabetes
      Education and Self Management for Ongoing and Newly Diagnosed) randomized
      controlled trial.
AB  - AIMS: To determine whether differences in the amount of time educators talk
      during a self-management education programme relate to the degree of change in
      participants' reported beliefs about diabetes. METHOD: Educators trained to be
      facilitative and non-didactic in their approach were observed delivering the
      DESMOND self-management programme for individuals newly diagnosed with Type 2
      diabetes. Observers used 10-s event coding to estimate the amount of time
      educators spoke during different sessions in the programme. Facilitative as
      opposed to didactic delivery was indicated by targets for levels of educator talk
      set for each session. Targets were based on earlier pilot work. Using the revised
      Illness Perceptions Questionnaire (IPQ-R) and the Diabetes Illness
      Representations Questionnaire (DIRQ), participants completed measures of:
      perceived duration of diabetes (timeline IPQ-R), understanding of diabetes
      (coherence IPQ-R), personal responsibility for influencing diabetes (personal
      responsibility IPQ-R), seriousness of diabetes (seriousness DIRQ) and impact on
      daily life (impact DIRQ), before and after the education programme. RESULTS:
      Where data from the event coding indicated educators were talking less and
      meeting targets for being less didactic, a greater change in reported illness
      beliefs of participants was seen. However, educators struggled to meet targets
      for most sessions of the programme. CONCLUSION: The amount of time educators talk
      in a self-management programme may provide a practical marker for the
      effectiveness of the education process, with less educator talk denoting a more
      facilitative/less didactic approach. This finding has informed subsequent
      improvements to a comprehensive quality development framework, acknowledging that
      educators need ongoing support to facilitate change to their normal educational
      style.

PMID- 19183319
TI  - Plasma triglycerides and LDL cholesterol are related in a parabolic fashion in
      the general population and patients with Type 2 diabetes mellitus: long-term
      follow-up results from the Hoorn study.
AB  - AIMS: Low-density lipoprotein cholesterol (LDL-C) levels are often fairly normal
      in Type 2 diabetes mellitus (DM). We anticipated that a parabolic relation
      between plasma triglycerides and LDL-C, as previously demonstrated in familial
      combined hyperlipidaemia (FCHL), might account for this phenomenon. METHODS: Our
      hypothesis was tested in 1343 subjects derived from the general population who
      were studied on two occasions 6 years apart (the Hoorn study). Three groups were
      constructed depending on plasma triglycerides: group A (individuals with both
      measurements below 1.5 mmol/l), group B (one measurement below and one above 1.5
      mmol/l) and group C (both measurements above 1.5 mmol/l). Diabetes status was
      ascertained by an oral glucose tolerance test. RESULTS: In a mixed linear model,
      a significant, positive relation between triglycerides and LDL-C was observed for
      males in group A (beta(a) = 0.5, P < 0.001) and group B (beta(b) = 0.2, P <
      0.001), whereas a significant negative relation was found for males in group C
      (beta(c) = -0.2, P = 0.003). The regression slopes did not differ between
      diabetic and non-diabetic subjects. Similar results were obtained for women, with
      the exception that the relation was not significantly negative in group C
      (beta(c) = -0.1, P = 0.4). CONCLUSION: Plasma triglycerides and LDL-C are related
      in a parabolic fashion, not only in FCHL, but also in the general population and
      Type 2 DM. These findings aid our interpretation of typical dyslipidaemia and the
      effects of treatment that are frequently observed in hypertriglyceridaemic
      states.

PMID- 19183320
TI  - Methodology problems in using eGFR to investigate the prevalence of renal
      anaemia.

PMID- 19183322
TI  - Beneficial effects of once-daily liraglutide, a human glucagon-like peptide-1
      analogue, on cardiovascular risk biomarkers in patients with Type 2 diabetes.

PMID- 19183324
TI  - Mesocolic plane surgery: just plain surgery?

PMID- 19183325
TI  - The cost of laparoscopic colorectal surgery.

PMID- 19183326
TI  - Pitfall of faecal occult blood test.

PMID- 19183327
TI  - Enhanced recovery programmes and colorectal surgery: does the laparoscope confer
      additional advantages?
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS) protocols aim to reduce
      postoperative lengths of stay (LOS). Laparoscopic surgery shares the same
      objective. Whether or not laparoscopic surgery conveys additional benefits over
      and above those achievable with ERAS alone is unclear. METHOD: A review of the
      literature from January 1966 to June 2008 was performed. Randomized trial and
      case series investigating the role of laparoscopic surgery within ERAS protocols
      were included. These were assessed for LOS, readmissions, return of gut function,
      quality of life and cost of treatment. RESULTS: Four publications from three
      randomized trials and another seven case series were identified. Two randomized
      trials revealed no difference in the LOS and readmission rates between ERAS when
      used alone and ERAS with the inclusion of laparoscopic surgery. However, a third
      trial revealed a significantly shorter LOS and a lower readmission rate in the
      ERAS and laparoscopic group. CONCLUSION: The limited evidence presently available
      suggests that no further benefit is obtained by the inclusion of laparoscopic
      surgery in ERAS protocols. Further research is needed to derive more definitive
      conclusions.

PMID- 19183328
TI  - A study of the functional aberration of the pouch in anorectal malformation
      associated with congenital pouch colon.
AB  - OBJECTIVE: There are no in vitro studies of congenital pouch colon (CPC)
      associated with anorectal malformation (ARM) to understand its mechanism of
      contractility. There is no consensus regarding the utilization of the CPC in
      repair of anorectal malformation. In view of the above, it was decided to carry
      out detailed in vitro physiological study of the excised CPC. METHOD: The excised
      specimens of CPC were taken and 15- to 20-mm long both longitudinal and
      transverse strips of muscle were obtained both from the proximal and distal part.
      Contraction was recorded using software chart-5 for windows. Drugs used were
      acetylcholine, histamine, adrenaline, atropine and pheniramine maleate. The
      amplitude of contractions was converted to tension gram and then the tension so
      developed was expressed as tension per unit mass (per gram of wet tissue).
      RESULTS: There were total of 21 specimens of high ARM with CPC. Five specimens
      were of the complete pouch, which did not show a response to any drug and the
      remaining 16 had an incomplete pouch. The mean longitudinal and circular muscle
      contractions of these 16 samples were statistically higher for the proximal
      segment than the distal segment both for acetylcholine and histamine. The effect
      of atropine was not significant but that of adrenaline and pheniramine maleate
      were significant on the distal segment muscle. CONCLUSION: Congenital pouch colon
      being deficient or having poorly developed receptors in their wall can not
      function properly as a reservoir for faeces and, hence, it should be excised to
      allow adequate function.

PMID- 19183329
TI  - The role of SMAD4 in early-onset colorectal cancer.
AB  - OBJECTIVE: Chromosomal loss within the region of 18q and loss of SMAD4 expression
      have been reported to be frequent somatic events during colorectal cancer tumour
      progression; however, their associations with age at onset have not been widely
      studied. METHOD: We analysed 109 tumours from a population-based case-family
      study based on colorectal cancers diagnosed before the age of 45 years. These
      patients with early-onset colorectal cancer had been previously screened for germ
      line mismatch repair gene mutations, microsatellite instability (that included
      the mononucleotide repeat in TGFbetaRII) and somatic k-ras mutations. We measured
      SMAD4 protein expression using immunohistochemistry and SMAD4 copy number using
      quantitative real-time PCR. RESULTS: Loss of SMAD4 protein expression was
      observed in 27/109 (25%) of cancers tested and was more commonly observed in
      rectal tumours (15/41, 36%) when compared with tumours arising in the colon
      (11/66, 17%) (P = 0.04). There was no association between SMAD4 protein
      expression and TGFbetaR11 mutation status, SMAD4 copy number, family history, MSI
      status, tumour stage or grade. CONCLUSION: Loss of SMAD4 expression is a common
      feature of early-onset colorectal tumours as it is in colorectal cancers
      diagnosed in other age-groups. Taken together, the molecular pathways (genetic
      and epigenetic) now known to be involved in early-onset colorectal cancer only
      explain a small proportion of the disease and require further exploration.

PMID- 19183330
TI  - Colonic diverticulitis: a prospective analysis of diagnostic accuracy and
      clinical decision-making.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of clinical evaluation and cross
      sectional imaging modalities such as ultrasound and computed tomography for
      patients with suspected colonic diverticulitis and to determine the value of
      these examinations in clinical decision-making. METHOD: A prospective analysis
      was conducted of 802 consecutive patients that presented with abdominal pain at
      the emergency department. Initial clinical diagnoses and management proposals
      were compared to the final diagnoses and therapeutic strategies for all patients.
      RESULTS: Fifty-seven patients were identified with colonic diverticulitis as the
      final diagnosis. The positive and negative predictive values for the clinical
      diagnosis of colonic diverticulitis were 0.65 and 0.98 respectively. Additional
      cross-sectional imaging had a positive and negative predictive value of
      respectively 0.95 and 0.99 or higher. These additional examinations led to a
      correct change of the initial clinical diagnosis in 37% of the patients, and a
      change in management in only 7%. CONCLUSION: The accuracy of the clinical
      diagnosis for colonic diverticulitis is low. Ultrasound and computed tomography
      have superior diagnostic accuracy but these examinations rarely change the
      initial management proposal.

PMID- 19183331
TI  - Hand-assisted laparoscopic surgery may be a useful tool for surgeons early in the
      learning curve performing total abdominal colectomy.
AB  - OBJECTIVE: We evaluated outcomes after hand-assisted (HALC) and straight
      laparoscopic (LC) techniques for the initial laparoscopic total abdominal
      colectomy (TAC) procedures performed by surgeons starting their laparoscopic
      careers. METHOD: The first eight HALC cases of two surgeons performing TAC by
      this technique (Group A) were compared with the first (Group B) and last eight
      (Group C) TAC cases of three surgeons performing LC. Groups A and B were compared
      with a matched group of open total colectomy cases (Group D) and to the eight
      cases performed by an experienced surgeon (Group E). Demographics, intra
      operative and postoperative outcomes including operation time, morbidity,
      conversion and readmission rates and length of hospital stay (LOS) were compared
      using Wilcoxon or Chi-squared tests. RESULTS: Demographics of the patients were
      similar. Groups A, B C and E had similar operating time (P = 0.10) which was
      significantly longer than Group D (P < 0.0001). Morbidity (P = 0.75) and
      readmission rates were similar (P = 0.89). Conversion rate was significantly
      higher for Group B (Group B: 41.7%vs Group A: 0%, P = 0.008), in the early
      period. LOS was comparable between minimally invasive groups but significantly
      shorter than open surgery group (P = 0.0005). For Groups A and C, operating time
      (P = 0.55), conversion rate (P = 0.11), morbidity (P = 0.83) and LOS (P = 0.12)
      were similar. CONCLUSIONS: Hand-assisted laparoscopic colectomy may be associated
      with a significantly shorter learning curve for TAC as results are better than
      early LC and comparable with LC performed by experienced laparoscopic surgeons.
      It may be a better option for surgeons early in their laparoscopic career.

PMID- 19183332
TI  - Noncolonic cancer stem cells in bone marrow of colorectal cancer patients.
AB  - OBJECTIVE: To investigate whether preoperative noncolonic cancer stem cells in
      bone marrow (BM) of R0 colorectal cancer (CRC) patients are cancer cells and
      impact on liver metastases (LM) rates. METHOD: Prospective data on continuous CRC
      patients were collected from five centres. Bone marrow aspirates, taken at
      laparotomy, were sent to a single lab. Noncolonic cancer stem cells were defined
      according to UICC. A quantity of 3 x 10(6) BM cells per patient was processed
      with monoclonal antibodies against cytokeratin 20. APC or p53 gene mutation and
      microsatellite instability (MSI) were assessed in primary tumours (PT) by single
      strand conformation polymorphism. Noncolonic cancer stem cells in BM of PT
      mutation or MSI-positive patients were isolated with immunobeads coated with
      magnetically labelled anti-human epithelial antigen antibody and DNA-screened for
      mutations. RESULTS: Although 199 patients were enrolled, 162 patients were
      available for analysis. No patients were lost to follow-up. Twenty-five (2-170)
      noncolonic cancer stem cells were found in BM of 40 patients. Twenty-two patients
      developed LM at 36-month follow-up. Adenomatous polyposis coli (APC) or p53 gene
      mutation or MSI were identified in the PT of 78 patients. The same gene mutations
      or MSI were not found in noncolonic cancer stem cells of the BM of these
      patients. After adjustment, there was no significant effect of confounding
      factors. Noncolonic cancer stem cells in BM had no impact on LM rates, cancer
      specific death rates, or all death rates. CONCLUSIONS: Preoperative noncolonic
      cancer stem cells in BM of R0 CRC patients were not cancer cells and had no
      impact on LM rates.

PMID- 19183333
TI  - Reduced neorectal capacitance is a more important factor for impaired defecatory
      function after rectal resection than the anal sphincter pressure.
AB  - OBJECTIVE: The role of the diverse anorectal diagnostic tools like manometry and
      determination of the preception threshold and the maximal tolerable volume is
      still a matter of debate. Currently, there is a scarcity of physiological data in
      the long-term follow-up of patients who underwent sphincter-preserving rectal
      resection. The aim of this study was therefore to perform these anorectal
      physiological measurements and to correlate the determined parameters with a
      faecal incontinence score. METHOD: In 45 patients, anorectal manometry,
      electromyography (EMG) and neorectal volume measurements were performed 21.6 +/-
      1.4 months after rectal resection. Additionally, patients answered questions to
      help in the determination of a modified faecal incontinence score. RESULTS: More
      than half of the patients had more than four bowel movements per day and suffered
      from defecatory urgency, evacuation and discrimination problems. Manometric data
      were not related to any functional deficits. In contrast, perception threshold
      and maximal tolerable volume were correlated with the faecal incontinence score.
      CONCLUSION: Defecatory problems especially after radiochemotherapy are still
      common after rectal resection and the satisfactory functionality post resection
      should not be oversimplified to just the number of bowel movements. A
      precondition of an adequate defecation is not only the integrity of the sphincter
      muscles, but also the recovery of the rectal reservoir function.

PMID- 19183334
TI  - Hypofibrinolysis is a risk factor for arterial thrombosis at young age.
AB  - The relationship between defective fibrinolysis and arterial thrombosis is
      uncertain. The evaluation of the plasma fibrinolytic potential might provide
      stronger evidence linking fibrinolysis to arterial thrombosis than the evaluation
      of the individual fibrinolytic factors. We determined the plasma fibrinolytic
      potential of 335 young survivors of a first arterial thrombosis, including
      coronary artery disease (n = 198), ischaemic stroke (n = 103) and peripheral
      artery disease (n = 34), enrolled in a population-based case-control study and of
      330 healthy individuals. Patients had significantly higher clot lysis times
      (CLTs) than the controls. Odds ratios (ORs) were calculated as a measure of
      relative risk. The OR for arterial thrombosis was determined in these subjects
      who had a CLT above the 60th, 70th, 80th, 90th and 95th percentiles of the values
      found in the control subjects. We found a progressive increase in risk of
      arterial thrombosis in subjects with hypofibrinolysis (OR: 1.7, 2.0, 2.3, 2.3 and
      2.9, respectively). Relative risk estimates obtained in the whole group were
      comparable those obtained in the event-subgroups. In conclusion, a low plasma
      fibrinolytic potential, found in 10% of the population, increases the relative
      risk of arterial thrombosis twofold. This points to an important contribution of
      hypofibrinolysis to the burden of arterial thrombosis.

PMID- 19183335
TI  - Comparative studies of brain evolution: a critical insight from the Chiroptera.
AB  - Comparative studies of brain size have a long history and contributed much to our
      understanding of the evolution and function of the brain and its parts. Recently,
      bats have been used increasingly as model organisms for such studies because of
      their large number of species, high diversity of life-history strategies, and a
      comparatively detailed knowledge of their neuroanatomy. Here, we draw attention
      to inherent problems of comparative brain size studies, highlighting limitations
      but also suggesting alternative approaches. We argue that the complexity and
      diversity of neurological tasks that the brain and its functional regions
      (subdivisions) must solve cannot be explained by a single or few variables
      representing selective pressures. Using an example we show that by adding a
      single relevant variable, morphological adaptation to foraging strategy, to a
      previous analysis a correlation between brain and testes mass disappears
      completely and changes entirely the interpretation of the study. Future studies
      should not only look for novel determinants of brain size but also include known
      correlates in order to add to our current knowledge. We believe that comparisons
      at more detailed anatomical, taxonomic, and geographical levels will continue to
      contribute to our understanding of the function and evolution of mammalian
      brains.

PMID- 19183336
TI  - In vivo functions of the prolyl-4-hydroxylase domain oxygen sensors: direct route
      to the treatment of anaemia and the protection of ischaemic tissues.
AB  - The prolyl-4-hydroxylase domain (PHD) 1-3 enzymes have been identified based on
      their ability to regulate the stability of hypoxia-inducible factor alpha
      subunits and thus to modify hypoxia-inducible gene expression. Transgenic mouse
      models provided insights into the isoform-specific functions of these oxygen
      sensors with physiological implications for angiogenesis, erythropoiesis/oxygen
      transport, cardiovascular function, metabolism and tissue homeostasis. This
      knowledge is important for the ongoing development of small molecule PHD
      inhibitors that are currently tested in preclinical and clinical trials for the
      treatment of anaemia and for cytoprotection. This review aims at summarizing the
      insights obtained from key mouse knock-out models as well as first experiences in
      the therapeutic application of PHD inhibitors.

PMID- 19183337
TI  - Possible common central pathway for resistin and insulin in regulating food
      intake.
AB  - AIM: Adipose tissue has been the object of intense research in the field of
      obesity and diabetes diseases in the last decade. Examination of adipocyte
      secreted peptides led to the identification of a unique polypeptide, resistin
      (RSTN), which has been suggested as a link between obesity and diabetes. RSTN
      plays a clearly documented role in blocking insulin (INS)-induced hypoglycaemia.
      As brain injection of INS affects feeding behaviour, we studied the possible
      interaction between INS and RSTN in food-deprived rats, measuring effects on food
      intake. In addition, we examined how RSTN might affect neuropeptide Y (NPY)
      induced feeding, as studies have shown that rat RSTN can interfere with the NPY
      system. METHODS: Overnight food-deprived rats were injected into the third brain
      ventricle (3V) with either INS (10 or 20 mUI), RSTN (0.1-0.4 nmol/rat), or saline
      before access to food. Another group of rats was injected into the 3V with RSTN
      alone, NPY alone or RSTN plus NPY. Their food intake and body weight were
      measured. RESULTS: Our results confirm the hypophagic effect of RSTN on food
      deprivation-induced food intake, and more importantly, show that RSTN neither
      potentiates nor blocks the effects of INS on food intake, but does reduce the
      hyperphagic effect of NPY. CONCLUSION: The observation that RSTN does not modify
      feeding INS-induced hypophagia, but does influence NPY-induced feeding, points to
      the possibility that RSTN may be involved in control of food intake through an
      NPY-ergic mechanism as INS.

PMID- 19183338
TI  - Administration of adalimumab in the treatment of Crohn's disease of the ileal
      pouch.
AB  - BACKGROUND: Crohn's disease (CD) of the pouch can develop in patients with ileal
      pouch-anal anastomosis (IPAA). Scant data are available on the treatment of this
      disease entity. AIM: To evaluate efficacy and safety of adalimumab in treating CD
      of the ileal pouch. METHODS: From June 2007 to June 2008, 17 IPAA patients with
      inflammatory (n = 10), fibrostenotic (n = 2) or fistulizing (n = 5) CD of the
      pouch treated with adalimumab were evaluated. Inclusion criteria were CD of the
      pouch who failed medical therapy and were otherwise qualified for permanent pouch
      diversion or excision. All qualified patients received the standard dosing
      regimen of subcutaneous injection adalimumab (160 mg at week 0, 80 mg at week 1,
      and 40 mg every other week thereafter). Complete clinical response was defined as
      resolution of symptoms. Partial clinical response was defined as improvement in
      symptoms. Endoscopic inflammation before and after therapy was recorded, using
      the Pouchitis Disease Activity Index (PDAI) endoscopy subscores. RESULTS: The
      median age was 36 years with 12 patients (70.6%) being male. At 4 weeks, seven
      patients (41.2%) had a complete symptom response and 6 (35.3%) had a partial
      response. There was also a significant improvement in the PDAI endoscopy
      subscores at week 4 (P < 0.05). At the last follow-up (median of 8 weeks), eight
      patients (47.1%) had a complete symptom response and 4 (23.5%) had a partial
      response. Four patients (23.6%) developed adverse effects. Three patients (17.7%)
      eventually had pouch failure after failing to respond to adalimumab therapy.
      CONCLUSION: Adalimumab appeared to be well-tolerated and efficacious in treating
      CD of the pouch in this open-labelled induction study.

PMID- 19183340
TI  - Mechanism of action of metformin in nonalcoholic steatohepatitis.

PMID- 19183339
TI  - Efficacy and complications of adalimumab treatment for medically-refractory
      Crohn's disease: analysis of nationwide experience in Scotland (2004-2008).
AB  - BACKGROUND: Adalimumab is a second generation humanized anti-tumour necrosis
      factor (TNF) monoclonal antibody with established efficacy in Crohn's disease
      (CD). AIMS: To evaluate the efficacy and safety of adalimumab on a nationwide
      clinical setting. METHODS: We used the Scottish Society of Gastroenterology
      network to identify and follow up the clinical outcomes of patients with CD
      treated with adalimumab over a 4-year period (2004-2008). RESULTS: A total of 98
      patients received adalimumab - 100.5 patient follow-up years were recorded (64.3%
      females; median age at diagnosis of 20.7 years; 88.8% treated with 80/40 mg
      induction regimen. Eighty eight (89.8%) had previous infliximab with 29 (32.9%)
      primary nonresponders; 32 (32.6%) were corticosteroid-dependent; 47 (47.9%) were
      intolerant/resistant to most immunosuppressive therapies (two or more). In all,
      60% of patients were in clinical remission at 1-year follow-up, with 30% and 55%
      requiring dose escalation to weekly therapy at 1-and 2-year follow-up
      respectively. Overall, 29 (29.6%) patients developed complications with eight
      nonfatal serious (8.2%) adverse events and 2 (2.0%) case fatalities (sepsis
      following perforation and disseminated colorectal cancer, respectively).
      CONCLUSIONS: Adalimumab is efficacious in severe and refractory CD in the
      clinical setting, although there remain significant therapy- and disease-related
      risks of serious complications.

PMID- 19183342
TI  - Array comparative genomic hybridization in retinoma and retinoblastoma tissues.
AB  - In retinoblastoma, two RB1 mutations are necessary for tumor development.
      Recurrent genomic rearrangements may represent subsequent events required for
      retinoblastoma progression. Array-comparative genomic hybridization was carried
      out in 18 eye samples, 10 from bilateral and eight from unilateral retinoblastoma
      patients. Two unilateral cases also showed areas of retinoma. The most frequent
      imbalance in retinoblastomas was 6p gain (40%), followed by gains at 1q12-q25.3,
      2p24.3-p24.2, 9q22.2, and 9q33.1 and losses at 11q24.3, 13q13.2-q22.3, and
      16q12.1-q21. Bilateral cases showed a lower number of imbalances than unilateral
      cases (P = 0.002). Unilateral cases were divided into low-level (< or = 4) and
      high-level (> or = 7) chromosomal instability groups. The first group presented
      with younger age at diagnosis (mean 511 days) compared with the second group
      (mean 1606 days). In one retinoma case ophthalmoscopically diagnosed as a benign
      lesion no rearrangements were detected, whereas the adjacent retinoblastoma
      displayed seven aberrations. The other retinoma case identified by retrospective
      histopathological examination shared three rearrangements with the adjacent
      retinoblastoma. Two other gene-free rearrangements were retinoma specific. One
      rearrangement, dup5p, was retinoblastoma specific and included the SKP2 gene.
      Genomic profiling indicated that the first retinoma was a pretumoral lesion,
      whereas the other represents a subclone of cells bearing 'benign' rearrangements
      overwhelmed by another subclone presenting aberrations with higher 'oncogenic'
      potential. In summary, the present study shows that bilateral and unilateral
      retinoblastoma have different chromosomal instability that correlates with the
      age of tumor onset in unilateral cases. This is the first report of genomic
      profiling in retinoma tissue, shedding light on the different nature of lesions
      named 'retinoma'.

PMID- 19183343
TI  - Candidate gene association study for noise-induced hearing loss in two
      independent noise-exposed populations.
AB  - Millions of people are daily exposed to high levels of noise. Consequently, noise
      induced hearing loss (NIHL) is one of the most important occupational health
      hazards worldwide. In this study, we performed an association study for NIHL
      based on a candidate gene approach. 644 Single Nucleotide Polymorphisms (SNPs) in
      53 candidate genes were analyzed in two independent NIHL sample sets, a Swedish
      set and part of a Polish set. Eight SNPs with promising results were selected and
      analysed in the remaining part of the Polish samples. One SNP in PCDH15
      (rs7095441), resulted in significant associations in both sample sets while two
      SNPs in MYH14 (rs667907 and rs588035), resulted in significant associations in
      the Polish sample set and significant interactions with noise exposure level in
      the Swedish sample set. Calculation of odds ratios revealed a significant
      association of rs588035 with NIHL in the Swedish high noise exposure level group.
      Our studies suggest that PCDH15 and MYH14 may be NIHL susceptibility genes, but
      further replication in independent sample sets is mandatory.

PMID- 19183344
TI  - Robust quantitative trait association tests in the parent-offspring triad design:
      conditional likelihood-based approaches.
AB  - Association studies, based on either population data or familial data, have been
      widely applied to mapping of genes underlying complex diseases. In family-based
      association studies, using case-parent triad families, the popularly used
      transmission/disequilibrium test (TDT) was proposed for avoidance of spurious
      association results caused by other confounders such as population
      stratification. Originally, the TDT was developed for analysis of binary disease
      data. Extending it to allow for quantitative trait analysis of complex diseases
      and for robust analysis of binary diseases against the uncertainty of mode of
      inheritance has been thoroughly discussed. Nevertheless, studies on robust
      analysis of quantitative traits for complex diseases received relatively less
      attention. In this paper, we use parent-offspring triad families to demonstrate
      the feasibility of establishment of the robust candidate-gene association tests
      for quantitative traits. We first introduce the score statistics from the
      conditional likelihoods based on parent-offspring triad data under various
      genetic models. By applying two existing robust procedures we then construct the
      robust association tests for analysis of quantitative traits. Simulations are
      conducted to evaluate empirical type I error rates and powers of the proposed
      robust tests. The results show that these robust association tests do exhibit
      robustness against the effect of misspecification of the underlying genetic model
      on testing powers.

PMID- 19183345
TI  - Testing for linkage and Hardy-Weinberg disequilibrium.
AB  - This paper concerns several important points when testing for Hardy-Weinberg
      equilibrium (HWE) and linkage disequilibrium (LD) in genetics. First, we
      challenge the necessity of using exclusively two-sided tests for LD. Next, we
      show that the exact 2-sided tests based on the most popular measures of LD are
      not equivalent, and neither are the standard statistical tests even though the 1
      sided tests are equivalent. We show how this results in different inference about
      LD for two data sets consisting of small groups of markers. Finally, we advocate
      the use of the conditional p-value for both LD and HWE testing. An important
      advantage of this p-value is that equivalent 1-sided tests are transformed into
      equivalent 2-sided tests.

PMID- 19183346
TI  - Pearson's test, trend test, and MAX are all trend tests with different types of
      scores.
AB  - Pearson's test is one of the most commonly used statistics for testing genetic
      association of case-control data. The trend test is another one which assumes a
      dose-response model between the risk of the disease and genotypes. To apply the
      trend test, a set of ordered scores is assigned a priori based on the underlying
      genetic model. Pearson's test is model-free and robust, but is less powerful for
      common genetic models. MAX is another robust test statistic, which takes the
      maximum of the trend tests over a family of scientifically plausible genetic
      models. We show that the three test statistics are all trend tests but with
      different types of scores; whether the scores are prespecified or data-driven, or
      whether the scores are ordered (restricted) or not ordered (unrestricted). We
      then provide insights into power performance of the three tests when the
      underlying genetic model is unknown and discuss which test to use for the
      analyses of case-control genetic association studies.

PMID- 19183347
TI  - Variants in intron 13 of the ELMO1 gene are associated with diabetic nephropathy
      in African Americans.
AB  - Variants in the engulfment and cell motility 1 (ELMO1) gene are associated with
      nephropathy due to type 2 diabetes mellitus (T2DM) in a Japanese cohort. We
      comprehensively evaluated this gene in African American (AA) T2DM patients with
      end-stage renal disease (ESRD). Three hundred and nine HapMap tagging SNPs and 9
      reportedly associated SNPs were genotyped in 577 AA T2DM-ESRD patients and 596 AA
      non-diabetic controls, plus 43 non-diabetic European American controls and 45
      Yoruba Nigerian samples for admixture adjustment. Replication analyses were
      conducted in 558 AA with T2DM-ESRD and 564 controls without diabetes. Extension
      analyses included 328 AA with T2DM lacking nephropathy and 326 with non-diabetic
      ESRD. The original and replication analyses confirmed association with four SNPs
      in intron 13 (permutation p-values for combined analyses = 0.001-0.003), one in
      intron 1 (P = 0.004) and one in intron 5 (P = 0.002) with T2DM-associated ESRD.
      In a subsequent combined analysis of all 1,135 T2DM-ESRD cases and 1,160
      controls, an additional 7 intron 13 SNPs produced evidence of association (P =
      3.5 x 10(-5)- P = 0.05). No associations were seen with these SNPs in those with
      T2DM lacking nephropathy or with ESRD due to non-diabetic causes. Variants in
      intron 13 of the ELMO1 gene appear to confer risk for diabetic nephropathy in AA.

PMID- 19183348
TI  - Effects of alendronate on a disintegrin and metalloproteinase with thrombospondin
      motifs expression in the developing epiphyseal cartilage in rats.
AB  - A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) have been
      reported to play a role in the degradation of aggrecan, a major component of
      cartilage. This study was performed to examine the effects of alendronate on the
      expression of ADAMTS in developing femoral epiphyseal cartilage. Primary cultured
      chondrocytes from this cartilage were treated with alendronate in vitro and
      postnatal day 1 rats were injected subcutaneously with alendronate (1 mg/kg)
      every second day in vivo. The number of cultured chondrocytes and their aggrecan
      mRNA levels were unaffected by the alendronate treatment at 10(-6) to 10(-4) M
      concentrations. The mRNA levels of ADAMTS-1, -2 and -9 in chondrocytes were also
      unaffected. However, the levels of ADAMTS-5 and -4 were reduced significantly by
      the same treatment. The thickness of the proliferating chondrocyte layers and the
      aggrecan mRNA levels in the epiphysis were unaffected by the alendronate
      treatment in vivo. However, the hypertrophied chondrocyte layers became
      significantly thicker, and the size of the secondary ossification centre was
      reduced significantly by the same treatment (P < 0.05). Both ADAMTS-4 and -5 mRNA
      expressions were also reduced significantly in vivo. The immunoreactivity against
      ADAMTS-4 was seen in hypertrophied chondrocytes and reduced significantly by the
      alendronate treatment. These results suggested that alendronate can inhibit the
      degradation of aggrecan in the articular cartilage by downregulating the
      expression of matrix enzymes such as ADAMTS-4 and -5.

PMID- 19183349
TI  - Macroanatomical investigation of the aorticorenal ganglion in 1-day-old infant
      sheep.
AB  - The aorticorenal gland belongs to the paired splanchnic ganglion, which is the
      main component of the coeliac plexus. It lies near the renal artery and
      suprarenal gland. The research was conducted on 13 1-day-old infant sheep - eight
      males and five females. Based on the conducted studies, it was concluded that the
      aorticorenal ganglion is characterized by the variable location in relation to
      the abdominal aorta, renal artery, caudal vena cava and suprarenal gland
      (holotopy), the thoracic and lumbar segment of the vertebral column (skeletotopy)
      (between L(1) and L(3)) and also a different shape (elongated, round, triangular,
      oval) as well as variable length (the aorticorenal ganglion is longer on the left
      side of the body; 2.72 mm) and distance from the caudal end of the suprarenal
      gland (longer on the left side of the body; 8.34 mm). With regard to the sex of
      the animal, the ganglion is the longest on the left side in ewes (3.02 mm), while
      in rams it is the longest on the right side (2.68 mm). Regarding the division
      according to sex, the longest segment was observed on the right side in ewes
      (9.27 mm), and the shortest segment in rams was also on the right side (6.84 mm).

PMID- 19183351
TI  - The morphology of the cervico-thoracic sympathetic system in donkeys (Equus
      asinus L.).
AB  - Five adult donkeys of both sexes, used in applied anatomy classes, and perfused
      with formalin for teaching purposes, constituted the study material. Ganglion
      cervicale caudale of the examined materials has observed to exhibit individually
      variable situation as to extend on the left side of the median line, at the
      alignment of the first and second intercostal spaces and on the right side
      between the level of the first and third costa. The ganglion extended more
      caudally on the right side of median line. The lateral surface of the ganglion
      was determined to be covered with the m. scalenus medius. On the both sides of
      the median plane, the ganglion cervicale caudale was seen to be situated on the
      lateral surface of the m. longus colli. On the left side, the ganglion overlapped
      the oesophagus in two cadavers and on the right side it was situated within a
      groove between the m. longus colli and trachea in three cadavers. The rami
      communicantes received by the ganglion cervicale caudale originated from the
      eighth cervical and first thoracic spinal segments. The ganglion cervicale
      caudale was formed by the coalescence of the last cervical and first three
      thoracic sympathetic ganglia. The ganglion cervicale caudale gave off branches
      that formed the rami communicantes, plexus cardiacus, n. vertebralis and ansa
      subclavia. One branch extended from the ganglion to the plexus brachialis. in one
      specimen, two sympathetic-parasympathetic communicating branches were observed to
      extend from the ansa subclavia and near by the origin of the truncus sympathicus
      to the n. vagus. In one of the donkeys examined, a branch originating from the
      ganglion cervicale caudale on the left side of the median plane was determined to
      end on the ligamentum arteriosum. A microscopic ganglion structure suggesting the
      existence of the ganglion cervicale medium was determined in a donkey.

PMID- 19183350
TI  - Macro-anatomical and karyological features of two blind mole rat subspecies
      (Rodentia: Spalacidae) from Turkey.
AB  - The morphometric and karyological analyses of 52 specimens belonging to the two
      subspecies of Nannospalax leucodon were examined from 14 localities in Turkey.
      Five karyotypic forms were recorded (2n = 60, the total numbers of chromosomal
      arms (NF) = 74, the numbers of autosomal arms (NFa) = 70; 2n = 60, NF = 76, NFa =
      72; 2n = 60, NF = 82, NFa = 78; 2n = 56, NF = 72, NFa = 68; 2n = 38, NF = 74, NFa
      = 70). The morphological features of two subspecies were studied using both
      numerical taxonomy and traditional methods. Thirty skull measurements and four
      baculum measurements were subjected to discriminant function analysis to find
      morphometric criteria allowing subspecies identification. Two subspecies were
      clearly separated from each other by macroanatomical characterictics and numeric
      characteristics. The first upper molar has four alveoli cubicles in young
      specimens of Nannospalax leucodon anatolicus, while M(1) has 1 cubicle in
      Nannospalax leucodon cilicicus. In the western subspecies (N. l. anatolicus, 2n =
      38), urethra openness is surrounded by three lobes. However, in the eastern
      subspecies (N. l. cilicicus, 2n = 60), there are two lateral lobes.

PMID- 19183352
TI  - Conformation and anatomical relations of the liver of llama (Lama glama).
AB  - Morphological studies of the liver of the llama are structural supportive to the
      clinical practice, surgery and specific diagnostic techniques. The aims of this
      study were first to determine the location of the organ and the direction of its
      major axis to project it to the abdominal wall, identifying visible and palpable
      bony references. Secondly, to characterize and determine anatomical relations of
      the surfaces, borders and angles of the llama liver, as well as, of its
      lobulation. Twenty adult llamas of both sexes and two foetuses of 6.5- and 7
      month-old were used. Llama liver is a post-diaphragmatic organ located in the
      cranial abdominal region, in the right hypochondrium, in relationship with the
      last six ribs. Dorsally, it can exceeds the last (twelfth) rib. Its major axis
      presents a cranio-ventral bent. Its shape is irregularly triangular. It presents
      two surfaces (parietal and visceral), three borders (cranial, caudal and ventral)
      and three angles (dorsal, cranial and caudal).

PMID- 19183353
TI  - Blood supply in the tongue of Nellore Bos indicus (Linnaeus, 1758).
AB  - Aspects of the vascularization of the tongue of Nellore Bos indicus (Linnaeus,
      1758) were evaluated through the vascular injection technique (with latex-type
      Neoprene 450, Du Pont do Brasil S.A. and Sulvinil coloring, Glassurit), fixed in
      formaldehyde at 7% and dissected with magnifying glass. The material was
      collected at Goias Carnes Freezer Warehouse in Goiania, Goias. It was found that
      the deep lingual artery penetrated the lower lateral region of the prominence of
      the dorsal area of the tongue, advancing rostrally between the hyoid bone and the
      hypoglossal muscle. In the intravisceral initial third, the artery represents the
      deep, sinuous continuation branch of the lingual artery, in which path the
      sublingual artery was stressed in the ventral plan. Then, the artery deepened in
      the interior of the hypoglossal muscles and genioglossal, supplying dorsal
      branches (from three to nine) for the lingual torus; from one to five dorsal
      collateral branches for the lingual cavity; and one or two ventral collateral
      branches. At the lingual apex, the artery undergoes bifurcation supplying
      collateral, dorsal and ventral branches with anastomoses between the parallel
      vessels in the same antimere and between branches of lower caliber hierarchy
      between opposite antemeres. The large presence of microvessels indicates a
      significant blood supply to the organ. These results, in comparison with those
      found in literature, suggest a peculiar vascular pattern for this cattle breed of
      Indian origin.

PMID- 19183354
TI  - [The average lifespan of a veterinary anatomist in a German speaking veterinary
      educational institution].
AB  - The average lifespan of veterinary anatomists was statistically analysed. All
      teachers who ever taught veterinary anatomy (formerly 'zootomy') and
      histology/embryology separately or in combination with other subjects in Germany,
      Austria and Switzerland were included in that circle. The observation period was
      from the foundation of the veterinary schools up to the present. We find that the
      average lifespan of this specific group is not different from that of the general
      population. Comparable previous opinions on the lifespan of anatomists, estimated
      as shorter than that of the general population by Hyrtl, and longer by Voss, are
      incorrect. This opportunity is also used to mention our time-honored; especially
      the early completed and aged colleagues.

PMID- 19183355
TI  - Swinging into action: the role of angular motion to increase peripheral arterial
      blood pressure.

PMID- 19183356
TI  - At least three levels of physiological control mechanisms ensure that arterial
      blood pressure is maintained in erect humans.

PMID- 19183357
TI  - Influence of sympathetic and AT-receptor blockade on angiotensin II and
      adrenergic agonist-induced renal vasoconstrictions in spontaneously hypertensive
      rats.
AB  - AIM: This study investigated the influence of angiotensin II (Ang II) receptor
      and adrenergic blockade on the renal vasoconstrictions caused by Ang II and
      adrenergic agonists in spontaneously hypertensive rats (SHR). METHODS: Forty
      eight SHR were subjected to 7 days of losartan (10 mg kg(-1) day(-1) p.o.),
      carvedilol (5 mg kg(-1) day(-1) p.o.) or losartan + carvedilol (10 mg kg(-1) day(
      1) + 5 mg kg(-1) day(-1) p.o.). On day 8, the rats were anaesthetized and renal
      vasoconstrictor experiments performed. One group of rats underwent acute
      unilateral renal denervation. RESULTS: There were significant (P < 0.05)
      reductions in the renal vasoconstrictor responses to noradrenaline,
      phenylephrine, methoxamine and Ang II after losartan and carvedilol treatments
      compared with that in untreated rats (all P < 0.05). However, in renally
      denervated SHR treated with carvedilol, the vasoconstrictor responses to all the
      vasoactive agents were enhanced compared with those in SHR with intact renal
      nerves treated with carvedilol. Intact SHR given both losartan and carvedilol
      showed greater renal vasoconstrictor responses to the vasoactive agents than when
      given either losartan or carvedilol alone (all P < 0.05). CONCLUSION: Carvedilol
      reduced the vasoconstrictor response to Ang II and all the adrenergic agonists in
      the presence of the renal nerves, but, following the removal of renal sympathetic
      activity, carvedilol enhanced the sensitivity of both renal alpha(1)
      adrenoceptors and AT(1) receptors to the vasoactive agents. Co-treatment with
      losartan and carvedilol reduced the renal vasoconstrictor responses to
      exogenously administered vasoactive agents but to a lesser extent than losartan
      or carvedilol alone. The results obtained demonstrate an interaction between Ang
      II receptors and adrenergic neurotransmission in the SHR.

PMID- 19183358
TI  - Severe generalized oedema with haemodynamic instability in a previously healthy
      patient (Case Presentation).

PMID- 19183359
TI  - Quantitative study on cerebral blood volume determined by a near-infrared
      spectroscopy during postural change in children.
AB  - AIM: To investigate changes in cerebral blood volume during standing in healthy
      children with or without abnormal cardiovascular responses. METHODS: We studied
      53 children (age, 10-15 years). Cerebral oxygenated haemoglobin (oxy-Hb) and
      deoxygenated Hb (deoxy-Hb) were non-invasively and continuously measured using
      near-infrared spectroscopy (NIRS) (NIRO 300, Hamamatsu Photomedics, Shizuoka,
      Japan) during active standing. Beat-to-beat arterial pressure was monitored by
      Portapres. RESULTS: Of 49 children with complete data acquisition, 33 had a
      normal cardiovascular response to the test (Group I) and 16 showed an abnormal
      response (Group II); nine with instantaneous orthostatic hypotension, three with
      postural tachycardia syndrome, three with neutrally mediated syncope and one with
      delayed orthostatic hypotension. At the onset of standing, Group II showed a
      significantly larger fall of oxy-Hb than Group I did (-2.9 +/- 2.8 micromol/L vs.
      -6.4 +/- 7.2 micromol/L, respectively, p < 0.05). During min 1 to 7 of standing,
      with one exception, changes in oxy-Hb were normally distributed over the level of
      -4 micromol/L in Group I. Group II also showed a significantly marked decrease in
      oxy-Hb compared to Group I. Decreases in oxy-Hb were not correlated with blood
      pressure changes. CONCLUSION: This study shows that precise change in cerebral
      blood volume caused by orthostatic stress can be determined by NIRS in children
      in a quantitative manner of NIRS. Children with abnormal circulatory responses to
      standing showed a significant reduction of oxy-Hb compared with normal
      counterparts, suggesting impairment of cerebral autoregulation in these children.

PMID- 19183360
TI  - Imaging patterns of brain injury in term-birth asphyxia.
AB  - AIM: To develop an extended asphyxia-score based on cerebral ultrasound (US) and
      MRI in order to gain further insight into the pathophysiology of asphyxia.
      PATIENTS AND METHODS: First week cerebral US and MRI of 80 asphyxiated term
      infants were scored according to a new scoring system based on separate grading
      of injury to deep grey matter and to (sub)cortical/white matter. Our findings
      were compared with published scoring systems. RESULTS: Six patterns of brain
      injury were derived: deep grey matter injury with either limited or extensive
      cortical involvement, damage to deep grey matter with watershed injury, isolated
      watershed injury, isolated white matter injury (leukomalacia) and isolated
      cortical necrosis. The mortality rate was considerable in patterns with extensive
      cortical injury. CONCLUSION: Six patterns of brain injury, following term-birth
      asphyxia were found using a new imaging score.

PMID- 19183367
TI  - Pilonidal sinus: has off-midline closure become the gold standard?

PMID- 19183368
TI  - Acute-care surgical services: a personal perspective.

PMID- 19183369
TI  - Prognostic factors and the treatment of the negative neck in oral carcinoma.

PMID- 19183370
TI  - Functional impairment after latissimus dorsi flap.

PMID- 19183372
TI  - Acute-care surgical service: a change in culture.
AB  - The provision of acute surgical care in the public sector is becoming
      increasingly difficult because of limitation of resources and the
      unpredictability of access to theatres during the working day. An acute-care
      surgical service was developed at the Prince of Wales Hospital to provide acute
      surgery in a more timely and efficient manner. A roster of eight general surgeons
      provided on-site service from 08.00 to 18.00 hours Monday to Friday and on-call
      service in after-hours for a 79-week period. An acute-care ward of four beds and
      an operating theatre were placed under the control of the rostered acute-care
      surgeon (ACS). At the end of each ACS roster period all patients whose treatment
      was undefined or incomplete were handed over to the next rostered ACS. Patient
      data and theatre utilization data were prospectively collected and compared to
      the preceding 52-week period. Emergency theatre utilization during the day
      increased from 57 to 69%. There was a 11% reduction in acute-care operating after
      hours and 26% fewer emergency cases were handled between midnight and 08.00
      hours. There was more efficient use of the entire theatre block, suggesting a
      significant cultural change. Staff satisfaction was high. On-site consultant
      driven surgical leadership has provided significant positive change to the
      provision of acute surgical care in our institution. The paradigm shift in acute
      surgical care has improved patient and theatre management and stimulated a
      cultural change of efficiency.

PMID- 19183373
TI  - Prognostic factors in the surgical treatment of patients with oral carcinoma.
AB  - The aim of the study was to analyse the clinical outcome of patients treated
      surgically for oral carcinoma. A retrospective cohort study was undertaken of 356
      patients with oral cavity cancer whose clinicopathological information had been
      collected prospectively onto a dedicated head and neck database. Disease
      recurrence and survival were assessed. Neck metastases occurred in 42% of
      patients. Tumour thickness (both 2 and 5 mm) predicted the presence of nodal
      metastases. Both pathological T stage (P < 0.001) and tumour thickness cut-off of
      5 mm (P = 0.03) were independent predictors of disease-specific survival. With a
      median follow up of 41 months, overall survival at 5 years was 59% and disease
      specific survival was 73%. Patients with thick tumours have a high risk of nodal
      metastases and this supports the liberal use of elective selective neck
      dissection in patients with clinically negative necks.

PMID- 19183374
TI  - Safety of endoscopic retrograde cholangiopancreatography during pregnancy.
AB  - BACKGROUND: The risk of choledocholithiasis is expected to be higher during
      pregnancy. This is attributed to alteration in bile composition as well as
      biliary stasis that take place during gestation. There is significant concern
      regarding application of endoscopic procedures especially the more invasive ones
      for treatment of choledocholithiasis during pregnancy. Our aim was to provide an
      additional support to the efficacy and safety of endoscopic retrograde
      cholangiopancreatography (ERCP) in the management of biliary diseases during
      pregnancy. METHODS: The medical records of 10 pregnant patients who underwent
      ERCP at King Abdullah University Hospital, during the period from 2002 to 2007
      were reviewed. Pregnancy course and outcomes were followed up in all cases.
      Results were analysed and compared with published data on safety and efficacy of
      this procedure. RESULTS: The mean age for mothers was 24.3 years. The mean
      duration of gestation was 18.4 weeks. Two patients were in the first trimester,
      five were in their second trimester and another three in the third trimester. The
      main indication for ERCP was obstructive choledocholithiasis on ultrasound and
      liver function tests. Fetal radiation exposure was not routinely measured.
      During, or after, the procedure there was no need for tocolytic agents. Also
      there was no intrauterine fetal distress. Screening for congenital anomalies was
      negative in all cases. CONCLUSION: Major complications of biliary obstruction
      have been prevented through this procedure. Short-term follow up for all neonates
      whom mothers underwent ERCP during pregnancy supports its safety. However,
      specific long-term fetal complications of radiation exposure have not been
      investigated yet.

PMID- 19183375
TI  - En bloc paediatric kidney transplant: is this the best use of a scarce resource?
AB  - BACKGROUND: Kidney transplants using organs from paediatric cadaver donors are
      uncommon and technically difficult. It has become accepted practice to transplant
      both kidneys en bloc from donors of 5 years into a single recipient. We aim to
      compare outcomes of en bloc kidney (EBK) transplants versus single kidney (SK)
      transplants from cadaver donors of age 5 years and lesser. METHODS: Data reported
      to Australia and New Zealand Dialysis and Transplant Registry from 1989 to 2004
      were analysed. RESULTS: From donors 5 years of age and younger, there were 33 EBK
      and 38 SK transplants carried out. Overall graft survival rates at 1 and 5 years
      were 78 and 61%, respectively, in the EBK group and 63 and 55%, respectively, in
      the SK group (P = 0.94). Vascular thrombosis was the most common cause of early
      graft loss with an incidence of 11 and 18%, respectively, in the EBK and SK
      groups (P = 0.5). CONCLUSION: There is a trend towards a lower vascular
      thrombosis rate and a better long-term graft survival in EBK transplants. These
      transplants will remain a technical challenge for the surgeon and EBK transplants
      should remain the technique of choice for donors of 5 years and lesser.

PMID- 19183377
TI  - Death by midgut infarction: clinical lessons from 88 post-mortems in Auckland,
      New Zealand.
AB  - BACKGROUND: Mortality rates from acute arterial mesenteric ischaemia remain high.
      Early diagnosis is of prognostic importance; however, early features are often
      non-specific, necessitating a high index of suspicion and knowledge of the at
      risk patient. This study reviewed three decades of fatal cases in Auckland, New
      Zealand, to identify risk factors and associated pathologies that might help
      guide early diagnosis. Diagnostic delay was also evaluated. METHODS: Cases were
      identified through a pathology database maintained from 1977 to 2006. Autopsy
      reports were assessed together with available clinical detail. RESULTS: Eighty
      eight cases were recovered. Mean age was 75.4 years, with women predominating
      (57%). Thromboembolic occlusion was the leading cause, followed by thrombotic
      occlusion. Embolic sources included atrial disease, aortic disease and myocardial
      infarction. Patients routinely showed extensive comorbidities, especially
      cardiovascular. Pain was the most constant presenting symptom, but features were
      often subtle and clinicians frequently misdiagnosed more minor ailments. Of
      operated patients, 36% received operations within 6 h of admission, 33% within 24
      h, 17% at between 1 and 2 days, and the remainder between 2 and 12 days.
      CONCLUSION: Knowledge of risk factors defined here is important to guide early
      diagnosis of mesenteric ischaemia. Diagnostic delay is again shown to be
      significant and case experience gathered in this series may improve doctors'
      discernment when meeting this condition.

PMID- 19183378
TI  - Functional impairment after latissimus dorsi flap.
AB  - BACKGROUND: Available published reports suggest that loss of latissimus dorsi
      muscle following latissimus myocutaneous flap does not lead to functional
      impairment. However, significant functional impairment has been observed in
      clinical practice, prompting this study to evaluate the functional deficit in
      patients who had undergone reconstruction using latissimus dorsi muscle. METHODS:
      A retrospective review was undertaken between 1998 and 2003. Patients were
      identified from the audit of the plastic surgery unit at St Vincent's Hospital
      and recruited by direct telephone contact. They were assessed using the
      Disability of Arm, Shoulder and Hand questionnaire. RESULTS: There were 25
      participants. Eighteen completed their questionnaires. Six of 18 patients
      reported scores of 30 or more, which corresponded to a global moderate functional
      deficit. These patients were severely limited in their ability to carry out
      housework. Major postoperative complications were associated with high Disability
      of Arm, Shoulder and Hand scores (P = 0.028). Three of five patients involved
      with sports reported impaired performance in sports. The subgroup of four
      patients who underwent bilateral latissimus dorsi flaps also experienced
      significant morbidity with all four reporting moderate to severe impairment in
      their ability to return to gardening and/or sports. CONCLUSION: Patients
      undergoing this procedure should be fully informed of potential sequelae.
      Athletic patients and patients undergoing bilateral latissimus dorsi flaps should
      also be warned of possible reduced performance in sports. Alternatively,
      perforator cutaneous flaps, which preserve the latissimus muscle, should be
      chosen when feasible.

PMID- 19183376
TI  - Defining the role of surgery for complications after pancreatoduodenectomy.
AB  - BACKGROUND: Although mortality rates following pancreatoduodenectomy have
      drastically reduced over the last few decades, high morbidity rates have
      continued to trouble pancreatic surgeons across the world. Interventional
      radiology has reduced the need for re-exploration for complications following
      pancreatoduodenectomy. There remain specific indications for re-exploration in
      such scenarios. It is thus pertinent to identify those clinical scenarios where
      surgery still has a role in managing complications of pancreatoduodenectomy. The
      aim of the study was to define the role of surgery for dealing with complications
      following pancreatoduodenectomy. METHODS: One hundred and fifty-seven consecutive
      pancreatoduodenectomies carried out at a single institution between 1 January
      2001 and 28 February 2007, were analysed. The database was looked into to
      identify patients who underwent re-exploration for complications and to define
      the indications for the exploration in these patients. RESULTS: Out of the 157
      pancreatoduodenectomies, there were, in all, 39 complications (24.2%) in 38
      patients. Most of these complications were successfully managed conservatively
      and with the help of interventional radiology. Seventeen patients had to be re
      explored (10.8%). The indications were primarily for haemorrhage, clinically
      significant pancreatic leaks, biliary leaks, adhesive intestinal obstruction and
      burst abdomen. The overall mortality rate was 3.1%. The mortality rate in the
      patients undergoing re-exploration was 11.7%. CONCLUSION: Early haemorrhage (from
      the pancreatic stump or anastomotic line), clinically significant pancreatic
      anastomotic leak with discharge from the main wound and an early biliary
      anastomotic leak are prime indications for re-exploration in patients with
      complications following pancreatoduodenectomy.

PMID- 19183379
TI  - Mutant p53 and cyclin A1 protein expression in primary laryngeal squamous cell
      carcinomas do not correlate to second primary tumours of the head and neck.
AB  - BACKGROUND: Field cancerization is a feature of head and neck squamous cell
      carcinoma. No biological marker in the index tumour has been correlated to the
      development of second primary tumours (SPT). Cyclin A1 is a cell cycle regulator
      and a downstream target of p53. This study assessed predictive correlation of
      cyclin A1 and mut-p53 with clinicopathological parameters and occurrence of (SPT)
      in the head and neck. METHODS: Using immunohistochemistry 106 patients treated
      for primary laryngeal squamous cell carcinoma were investigated for expression of
      cyclin A1 and mut-p53. RESULTS: Expression of cyclin A1 and mut-p53 were noted in
      83 of 106 (78.3%) and 25 of 106 (23.6%) patients. There was a weak but
      significant correlation between mut-p53 and cyclin A1 (r = 0.301, P = 0.002)
      expression. During the follow-up period (median 41.0 months (range 1-205
      months)), 21 of 106 (19.8%) patients developed an SPT. There was no statistically
      significant correlation between the markers investigated and disease recurrence,
      SPT diagnosis or clinicopathological parameters. CONCLUSION: Second primary
      tumours are an intriguing problem in treatment of HNSCC and a predictive marker
      identifying those greatest at risk would be a leap forward.

PMID- 19183380
TI  - Audit of the Douglas Hocking Research Institute bone bank: ten years of non
      irradiated bone graft.
AB  - BACKGROUND: An audit performed in the use of non-irradiated femoral head bone
      graft at the Geelong Hospital over a 10-year period. While it is thought the non
      irradiated bone graft provides a better structural construct there is theoretical
      increased risk of infection transmission. METHODS: We performed a retrospective
      review of prospectively collected data in the use of non-irradiated bone
      allograft used from the Geelong Hospital Douglas Hocking Research Institute bone
      bank over a 10-year period. The review was performed using data collected from
      the bone bank and correlating it with the patient's medical record. All
      complications, including infections, related to the use of the allograft were
      recorded. RESULTS: We found that over the 10 years to 2004 that 811 femoral heads
      were donated, with 555 being used over 362 procedures in 316 patients. We
      identified a total of nine deep infections, of which seven were in joint
      replacements. Overall this was a 2.5% deep infection rate, which was lowered to
      1.4% if the previously infected joints that were operated on were excluded.
      CONCLUSION: The use of non-irradiated femoral head bone graft was safe in a
      regional setting.

PMID- 19183381
TI  - Melanoma antigen-1 mRNA combined with alpha-fetoprotein mRNA levels in peripheral
      blood of patients with hepatocellular carcinoma: a predictor of postoperative
      recurrence or metastasis?
AB  - BACKGROUND: The aim of the study was to identify whether melanoma antigen (MAGE)
      1 mRNA and alpha-fetoprotein (AFP) mRNA expressed in peripheral blood could be
      used to predict the recurrence and metastasis of hepatocellular carcinoma (HCC)
      after hepatectomy. METHODS: One hundred and forty-two HCC patients underwent
      hepatectomy. The control group includes 27 patients with chronic virus hepatitis
      and cirrhosis and 10 healthy volunteers. Peripheral blood samples were collected
      on the seventh day before operation, seventh day after operation and 30th day
      after operation. MAGE-1 mRNA and AFP mRNA were tested by nested reverse
      transcription polymerase chain reaction. Median follow up was 25.5 months (range
      4-40 months). Patient survival, disease-free survival and clinicopathological
      features were compared between patients with positive and negative MAGE-1 mRNA
      and/or AFP mRNA. RESULTS: The expression of MAGE-1 mRNA and/or AFP mRNA in
      peripheral blood was closely correlated to the pathological stage and the
      positive ratio of tumour cells in the peripheral blood (P < 0.01). There was
      recurrence and/or metastasis after operation in 55 of 142 HCC patients. Among the
      55 patients who had recurrence or metastasis, MAGE-1 mRNA and/or AFP mRNA in
      peripheral blood were persistently detected after operation in 38 patients and
      MAGE-1 mRNA and AFP mRNA turned to positive after operation in 14 patients. In
      contrast, no recurrence was found in 62 patients whose MAGE-1 mRNA and/or AFP
      mRNA turned to negative after operation. 88.1% (52 of 59) of patients with MAGE-1
      mRNA and/or AFP mRNA persistently positive after operation showed recurrence or
      metastasis, whereas only 3.6% patients (3 of 83) with the negative of MAGE-1 mRNA
      and/or AFP mRNA after operation showed recurrence or metastasis (P < 0.001).
      CONCLUSION: Melanoma antigen-1 mRNA combined with AFP mRNA in peripheral blood
      after hepatectomy is more sensitive and specific than AFP mRNA singly for
      predicting the recurrence and metastasis of the HCC patients, whereas
      preoperative transient detection is not.

PMID- 19183382
TI  - Aortic fat pad and atrial fibrillation: cardiac lymphatics revisited.
AB  - The lymphatics of the heart have not generated any broad or sustained interest
      among clinicians. Few publications on cardiac lymphatics are available, the
      anatomy is not routinely known and the true role of cardiac lymphatics remains
      doubtful. One important anatomical concept needing clarification is that of the
      lymphatic drainage of conduction tissue. The sinoatrial node lymphatic collector
      and right principal lymphatic trunk are both incorporated into the aortic fat pad
      of the ascending aorta and are the most frequently damaged lymphatic vessels
      during cardiac surgery. Thus, preservation of the aortic fat pad and its
      lymphatic collectors should reduce the incidence of new atrial fibrillation
      observed in patients after cardiac surgery. This review assesses current
      knowledge of cardiac lymphatics and shows their possible role in triggering
      arrhythmias in the postoperative period.

PMID- 19183383
TI  - Four port-site recurrences of gall bladder cancer after laparoscopic
      cholecystectomy.

PMID- 19183384
TI  - Small bowel obstruction due to enterolith expelled from duodenal diverticulum.

PMID- 19183392
TI  - Re: dilemma of small renal masses.

PMID- 19183393
TI  - Auto-amputation of penis due to carcinoma.

PMID- 19183394
TI  - Should we excise the foreskin?

PMID- 19183395
TI  - Traumatic neuroma of the right hepatic duct undertaken right hemihepatectomy.

PMID- 19183396
TI  - Giant parathyroid adenoma.

PMID- 19183397
TI  - Giant inguinal hernia containing right colon repaired using the prolene hernia
      system.

PMID- 19183398
TI  - Schwannoma tongue: a rare entity.

PMID- 19183399
TI  - Incidental liver lesion in a young boy.

PMID- 19183400
TI  - Dendritic cells--why can they help and hurt us.
AB  - Dendritic cells (DCs) show a Janus-like functional behavior. They help us by
      their orchestration of numerous immune responses to defend our body against
      invading pathogenic micro-organisms and also induce regulatory T cells to inhibit
      immune reactions against autoantigens as well as diverse harmless environmental
      antigens. However, DCs can also be of harm to us when misguided by their
      microenvironment as in allergic and autoimmune diseases or when DCs are targeted
      and exploited by microbes and cancer cells to evade the immune defense. This huge
      and diverse functional repertoire of DCs requires complex decision-making
      processes and the integration of multiple stimulatory and inhibitory signals.
      Although a given DC type has an extensive functionally plasticity, DCs are
      heterogeneous and individual DC subtypes are differentially distributed in
      tissues, express distinct sets of pattern recognition receptors and differ in
      their capacity to program naive T cells. With the help of transgenic mouse models
      and selective ablation of individual DC subtypes, we are just at the beginning of
      understanding the DC system in its complexity. Obtaining a more detailed
      knowledge of the DC system in mice and men holds strong promise for the
      successful induction of immunity and tolerance in therapeutic trials. This review
      presents the recent advances in the understanding of DC biology and discusses why
      and how DC can help and hurt us.

PMID- 19183401
TI  - Topical pimecrolimus and tacrolimus do not accelerate photocarcinogenesis in
      hairless mice after UVA or simulated solar radiation.
AB  - Pimecrolimus and tacrolimus are topical calcineurin inhibitors developed
      specifically for the treatment of atopic eczema. Experience with long-term use of
      topical calcineurin inhibitors is limited and the risk of rare but serious
      adverse events remains a concern. We have previously demonstrated the absence of
      carcinogenic effect of tacrolimus alone and in combination with simulated solar
      radiation (SSR) on hairless mice. The aim of this study is to determine whether
      pimecrolimus accelerates photocarcinogenesis in combination with SSR or
      pimecrolimus and tacrolimus accelerate photocarcinogenesis in combination with
      UVA. We used 11 groups of 25 hairless female C3.Cg/TifBomTac immunocompetent mice
      (n = 275). Pimecrolimus cream or tacrolimus ointment was applied on their dorsal
      skin three times weekly followed by SSR (2, 4, or 6 standard erythema doses, SED)
      or UVA (25 J/cm(2)) 3-4 h later. This was done up to 365 days in the SSR-treated
      groups and up to 500 days in the UVA-treated groups. Pimecrolimus did not
      accelerate the time for development of the first, second or third tumor in any of
      the groups. Median time to the first tumor was 240 days for the control-2SED
      group compared with pimecrolimus-2SED group (233 days), control-4SED group (156
      days) compared with pimecrolimus-4SED group (163 days) and control-6SED group
      (162 days) compared with pimecrolimus-6SED group (170 days). Only one mouse in
      each of the three UVA groups developed a tumor. We conclude that pimecrolimus in
      combination with SSR and both pimecrolimus and tacrolimus in combination with UVA
      do not accelerate photocarcinogenesis in hairless mice.

PMID- 19183402
TI  - Emergency thoracic ultrasound in the differentiation of the etiology of shortness
      of breath (ETUDES): sonographic B-lines and N-terminal pro-brain-type natriuretic
      peptide in diagnosing congestive heart failure.
AB  - OBJECTIVES: Sonographic thoracic B-lines and N-terminal pro-brain-type
      natriuretic peptide (NT-ProBNP) have been shown to help differentiate between
      congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD).
      The authors hypothesized that ultrasound (US) could be used to predict CHF and
      that it would provide additional predictive information when combined with NT
      ProBNP. They also sought to determine optimal two- and eight-zone scanning
      protocols when different thresholds for a positive scan were used. METHODS: This
      was a prospective, observational study of a convenience sample of adult patients
      presenting to the emergency department (ED) with shortness of breath. Each
      patient had an eight-zone thoracic US performed by one of five sonographers, and
      serum NT-ProBNP levels were measured. Chart review by two physicians blinded to
      the US results served as the criterion standard. The operating characteristics of
      two- and eight-zone thoracic US alone, compared to, and combined with NT-ProBNP
      test results for predicting CHF were calculated using both dichotomous and
      interval likelihood ratios (LRs). RESULTS: One-hundred patients were enrolled.
      Six were excluded because of incomplete data. Results of 94 patients were
      analyzed. A positive eight-zone US, defined as at least two positive zones on
      each side, had a positive likelihood ratio (LR+) of 3.88 (99% confidence interval
      [CI] = 1.55 to 9.73) and a negative likelihood ratio (LR-) of 0.5 (95% CI = 0.30
      to 0.82), while the NT-ProBNP demonstrated a LR+ of 2.3 (95% CI = 1.41 to 3.76)
      and LR- of 0.24 (95% CI = 0.09 to 0.66). Using interval LRs for the eight-zone US
      test alone, the LR for a totally positive test (all eight zones positive) was
      infinite and for a totally negative test (no zones positive) was 0.22 (95% CI =
      0.06 to 0.80). For two-zone US, interval LRs were 4.73 (95% CI = 2.10 to 10.63)
      when inferior lateral zones were positive bilaterally and 0.3 (95% CI = 0.13 to
      0.71) when these were negative. These changed to 8.04 (95% CI = 1.76 to 37.33)
      and 0.11 (95% CI = 0.02 to 0.69), respectively, when congruent with NT-ProBNP.
      CONCLUSIONS: Bedside thoracic US for B-lines can be a useful test for diagnosing
      CHF. Predictive accuracy is greatly improved when studies are totally positive or
      totally negative. A two-zone protocol performs similarly to an eight-zone
      protocol. Thoracic US can be used alone or can provide additional predictive
      power to NT-ProBNP in the immediate evaluation of dyspneic patients presenting to
      the ED.

PMID- 19183403
TI  - Changes in common melanocytic naevi after intense sun exposure: digital
      dermoscopic study with a 1-year follow-up.
AB  - BACKGROUND: Exposure to ultraviolet (UV) radiation induces acute changes in
      common melanocytic naevi (CMN). AIM: To analyse changes in size and dermoscopic
      structures of CMN in healthy individuals under the influence of intense sun
      exposure and to investigate effectiveness of sunscreen usage in preventing the
      appearance of dermoscopic changes. METHODS: The subjects were divided into an SS
      group and a non-SS group, according to whether they used sunscreen or not.
      Digital epiluminiscence microscopy (DELM) was performed before sun exposure and
      28 days and 1 year after the cessation of intense sun exposure. RESULTS: Eleven
      subjects with 60 naevi fulfilled the inclusion criteria. A significant increase
      in one diameter of the CMN was found 28 days after cessation of sun exposure,
      irrespective of sunscreen usage. There was no significant change in total
      dermoscopy score during the follow-up period in either the SS or non-SS group.
      There were definitive DELM changes at the 1-year follow-up in 10% of CMNs < 5 mm
      in size. Changes in pigmented network, globules and streaks were fully reversible
      in the remaining CMN. The use of sunscreen had no influence on these changes.
      CONCLUSIONS: The increases in the size of melanocytic naevi that we found 28 days
      after cessation of intense sun exposure are probably induced by UV radiation,
      whereas changes in DELM features that were not reversible in some small naevi at
      the 1-year follow-up could be related both to sun exposure and to the natural
      evolution of the naevi. The use of sunscreen does not seem to prevent these
      changes. Small naevi in low-risk young and middle-aged patients seem to be more
      prone to sun-induced DELM changes.

PMID- 19183404
TI  - Near-patient assays for diagnosis of influenza virus infection in adult patients.
AB  - Rapid and reliable diagnosis of influenza is essential for identification of
      contagious patients and effective patient management. Near-patient assays allow
      establishment of the diagnosis within minutes in young children, and this study
      aimed to evaluate near-patient assays in relation to the patient's age. A total
      of 194 patients with laboratory-confirmed influenza A/H3N2 virus infection,
      diagnosed within a prospective cohort study, were included. Cryopreserved
      nasopharyngeal swabs collected from these patients were tested by four near
      patient assays (Binax Now Influenza A&B, Quick S-Influ A/B, Influ-A&B Respi
      Strip, and Actim Influenza A&B). The main outcome measure was sensitivity of the
      near-patient assays in relation to the age of patients. The Binax Now, Quick S
      Influ, Influ-A&B Respi-Strip and Actim assays had overall sensitivities of 19%,
      18%, 26%, and 40%, respectively. The estimated sensitivity for influenza A/H3N2
      virus detection in nasopharyngeal swabs was 17-56% in children 1 year of age and
      decreased to 8-22% in patients 80 years of age (logistic regression). The
      sensitivity of the Influ-A&B Respi-Strip and Actim assays decreased significantly
      with increasing age (p 0.014 and p 0.033, respectively (logistic regression)), a
      trend for decrease was observed for the Binax Now assay (p 0.074 (logistic
      regression)), and the low sensitivity of the Quick S-Influ assay was similar in
      children and adults. Less than one-fourth of diagnosed influenza A/H3N2 virus
      infections can be identified in elderly patients using a near-patient assay.
      Consequently, near-patient assays are of limited value for confirming the
      diagnosis when influenza is clinically suspected in adults. Antiviral therapy and
      additional diagnostic procedures cannot be withheld on the basis of a negative
      near-patient assay result, particularly in adult patients.

PMID- 19183405
TI  - Intraoperative transesophageal echocardiography is beneficial for hemodynamic
      stabilization during left ventricular assist device implantation in children.
AB  - BACKGROUND: Mechanical circulatory support, with a left ventricular assist device
      (LVAD) is used in an increasing number of children for treatment of advanced
      heart failure as bridge-to-transplant. To date no data are available and no
      studies have defined the role of intraoperative transesophageal echocardiography
      (TEE) for hemodynamic stabilization during Centrimag Levitronix centrifugal pump
      implantation in children. METHODS: Children with therapy resistant heart failure,
      undergoing LVAD implantation using Berlin Heart Excor pediatric cannula connected
      to a Levitronix Centrifumag pump, are intraoperatively monitored using an Oldelft
      micromultiplane TEE. Intraoperative TEE is specially used to monitor right
      ventricular (RV) and left ventricular (LV) function, correct position of the
      cannulas and response to pharmacological treatment. RESULTS: In five consecutive
      patients RV function was assessed by TEE after starting LVAD Levitronix
      centrifugal pump. Initial RV failure presents with RV dilation and LV collapse.
      After titration of vasopressor and inotropic agents, RV contractility improved
      and thereby the filling of the LV. In one child, despite those measures the RV
      showed no improvement by TEE and a Levitronix right ventricular assist device to
      support the RV function was implanted as well. All patients could hemodynamically
      be stabilized before transport to the intensive care unit. CONCLUSION: The
      complex interaction of the RV and LV function and correct positioning of the
      cannula, during LVAD implantation in children with end-stage cardiac failure is
      improved by simultaneous visualization of cardiac performance of both ventricles
      and cannula positioning by means of intraoperative multiplane TEE.

PMID- 19183406
TI  - Analysis of RET, ZEB2, EDN3 and GDNF genomic rearrangements in 80 patients with
      Hirschsprung disease (using multiplex ligation-dependent probe amplification).
AB  - Hirschsprung disease (HSCR) is transmitted in a complex pattern of inheritance
      and is mostly associated with variants in the RET proto-oncogene. However, RET
      mutations are only identified in 15-20% of sporadic HSCR cases and solely in 50%
      of the familial cases. Since genomic rearrangements in particularly sensitive
      areas of the RET proto-oncogene and/or associated genes may account for the HSCR
      phenotype in patients without other detectable RET variants, the aim of the
      present study was to identify rearrangements in the coding sequence of RET as
      well as in three HSCR-associated genes (ZEB2, EDN3 and GDNF) in HSCR patients by
      using Multiplex Ligation-dependent Probe Amplification (MLPA). We have screened
      80 HSCR patients for genomic rearrangements in RET, ZEB2, EDN3 and GDNF and did
      not identify any deletion or amplification in these four genes in all patients.
      We conclude that genomic rearrangements in RET are rare and were not responsible
      for the HSCR phenotype in individuals without identifiable germline RET variants
      in our group of patients, yet this possibility cannot be excluded altogether
      because the confidence to identify variation in at least two percent of the
      individuals was only 95%.

PMID- 19183407
TI  - AKR-501 (YM477) a novel orally-active thrombopoietin receptor agonist.
AB  - Thrombopoietin (TPO) is the principal physiologic regulator of platelet
      production. We have searched for small molecule compounds that mimic the action
      of TPO by using human TPO receptor-expressed in Ba/F3 cells, resulting in the
      discovery of AKR-501 (YM477). AKR-501 specifically targeted the TPO receptor and
      stimulated megakaryocytopoiesis throughout the development and maturation of
      megakaryocytes just as rhTPO did. AKR-501, however, was shown to be effective
      only in humans and chimpanzees with high species specificity. Therefore, we
      examined the in vivo platelet-increasing effect of AKR-501 in human platelet
      producing non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice
      transplanted with human fetal liver CD34(+) cells. Daily oral administration of
      AKR-501 dose-dependently increased the number of human platelets in these mice,
      with significance achieved at doses of 1 mg/kg and above. The peak unbound plasma
      concentrations of AKR-501 after administration at 1 mg/kg in NOD/SCID mice were
      similar to those observed following administration of an active oral dose in
      human subjects. These results suggest that AKR-501 is an orally-active TPO
      receptor agonist that may be useful in the treatment of patients with
      thrombocytopenia.

PMID- 19183409
TI  - Monitoring of sympathetic tone to assess postoperative pain: skin conductance vs
      surgical stress index.
AB  - The number of fluctuations in skin conductance per second has been described as a
      potential tool for monitoring postoperative pain. More recently, the surgical
      stress index has shown promising correlations with intra-operative painful
      stimuli. We compared both methods for their ability to assess postoperative pain,
      in 100 postoperative patients who were also asked to quantify their level of pain
      at different time points in the recovery room. The number of fluctuations per
      second and surgical stress index were significantly different between pain
      scoring <or= 5/10 and > 5/10 on a numeric rating scale (mean (SE) number of
      fluctuations per second 0.12 (0.02) vs 0.21 (0.03), respectively; p = 0.017, and
      surgical stress index 57 (1.4) vs 64 (1.9) points, respectively; p = 0.001). Both
      number of fluctuations in skin conductance per second and surgical stress index
      identified timepoints with moderate to severe pain with only moderate sensitivity
      and specificity.

PMID- 19183408
TI  - A distinct type of cell in myocardium: interstitial Cajal-like cells (ICLCs).
AB  - The existence of a novel type of interstitial cells in the heart, interstitial
      Cajal-like cells (ICLCs), had been described for the first time in 2005. Their
      identification was mainly based on ultrastructural criteria: very long (tens up
      to hundreds of micrometres) and moniliform prolongations, which are extremely
      thin (less than 0.2 microm), below the resolving power of light microscopy.
      Myocardial ICLCs were also identified by methylene-blue vital staining, silver
      impregnation, and immunoreactivity for CD 34, vimentin, CD117/c-kit, etc.
      Although a series of studies provided evidence for the existence of ICLCs in
      human atria and rat ventricles, further investigations in other laboratories,
      using additional techniques, are required to substantiate the consistency of
      these findings. Here we provide further evidence for the existence of ICLCs in
      human and mammalian hearts (by transmission and scanning electron microscopy, as
      well as confocal laser scanning microscopy). Noteworthy, we confirm that ICLCs
      communicate with neighbouring cells via shedding (micro)vesicles. Although these
      so-called ICLCs represent a distinct type of cells, different from classical
      interstitial cells of Cajal, or fibroblasts, their role(s) in myocardium
      remain(s) to be established. Several hypotheses are proposed: (i) adult stromal
      (mesenchymal) stem cells, which might participate in cardiac repair/remodelling;
      (ii) intercellular signalling (e.g. via shedding microvesicles); (iii) chemo
      mechanical transducers and (iv) players in pacemaking and/or arrhytmogenesis, and
      so on.

PMID- 19183410
TI  - Precalcaneal congenital fibrolipomatous hamartoma.
AB  - Precalcaneal congenital fibrolipomatous hamartoma (PCFH) is a condition that is
      seldom reported in the paediatric literature and rarely in the dermatological
      literature. It has other disparate and confusing names and as histology is rarely
      obtained, the condition may be under-reported. We describe this disorder in the
      male twin of a pair of nonidentical twins.

PMID- 19183411
TI  - Autosomal dominant pericentral retinal dystrophy caused by a novel missense
      mutation in the TOPORS gene.
AB  - PURPOSE: This study aimed to identify the genetic cause of autosomal dominant
      pericentral retinal dystrophy (adPRD) in a large Norwegian family with 35
      affected members. METHODS: The family was characterized by clinical
      ophthalmological examination along with fundus photography, dark adaptometry and
      electroretinography. We performed a genome-wide linkage analysis followed by
      sequencing of a candidate gene to identify the mutation causing the disease.
      RESULTS: The ophthalmological examinations revealed an atypical form of retinitis
      pigmentosa (RP), which we prefer to call adPRD. Compared with classical RP, this
      phenotype has a favourable prognosis. Linkage analysis showed a linkage peak
      covering the most recently reported adRP gene TOPORS. This gene was sequenced in
      19 family members and a novel missense mutation, c.1205a>c, resulting in an amino
      acid substitution p.Q402P, was detected in all affected members. The mutation
      showed complete co-segregation with the disease in this family, with a LOD score
      of 7.3. It is located in a highly conserved region and alignment with the
      appropriate DNA sequence from other species shows complete conservation of this
      amino acid. The mutation was not detected in 207 healthy, unrelated controls of
      Norwegian origin. CONCLUSIONS: We present a novel mutation in the TOPORS gene co
      segregating with a distinct phenotype of adPRD in a large Norwegian family.

PMID- 19183413
TI  - Foveal function in children treated for amblyopia.
AB  - PURPOSE: This study aimed to evaluate foveal function, using three different
      methods, in children treated for monocular amblyopia. METHODS: A sample of 24
      otherwise healthy children with treated amblyopia and an age-matched control
      group of 25 healthy children were examined for best corrected visual acuity
      (BCVA) using a standard decimal (KM) chart and the computerized TriVA method at
      50% and 10% contrasts. Foveal function was also measured with the rarebit fovea
      test (RFT), which is included in the rarebit perimetry program package. This test
      uses very small and bright dots against a dark background. The result is
      expressed as mean hit rate (MHR). RESULTS: Amblyopic eyes showed significantly
      lower BCVA when evaluated with the KM chart and with the TriVA test at different
      contrast levels, compared with both fellow eyes and control eyes. No
      statistically significant difference between amblyopic and fellow eyes was found
      when foveal function was evaluated with the RFT (median MHRs 91.5% and 94.5%,
      respectively), although results for both amblyopic and fellow eyes were
      statistically lower than those of the control group (median MHR 97%) (p = 0.001
      and p = 0.046, respectively). This might indicate that the RFT provides different
      information about foveal function than conventional VA tests. CONCLUSIONS: The
      findings in the current study accord with those of other studies reporting
      abnormalities in the fellow eyes of previously treated amblyopic patients. These
      findings may reflect a general disturbance in the visual system rather than a
      monocular adaptation to refractive error or ocular motor disturbance.

PMID- 19183412
TI  - Effect of bromfenac ophthalmic solution on ocular inflammation following cataract
      surgery.
AB  - PURPOSE: This study compared the post-cataract surgery anti-inflammatory effects
      of topical treatment with 0.1% bromfenac, 0.1% betamethasone or both on
      postoperative anterior chamber inflammation and corneal swelling. METHODS:
      Seventy-two patients with no eye disease other than cataract were enrolled in a
      prospective, randomized study to undergo phacoemulsification combined with
      intraocular lens implantation. After cataract surgery, patients were randomized
      to treatment with bromfenac, betamethasone or both agents. Twenty-five eyes were
      assigned to bromfenac, 23 to betamethasone and 24 to the combined treatment
      group. Inflammatory reactions in the anterior chamber were measured with laser
      flare photometry preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1 and 2
      months postoperatively. Intraocular pressure (IOP) and corneal thickness were
      measured at the same time-points. Best corrected visual acuity (BCVA) was
      measured preoperatively and at 2 days, 1 and 2 weeks, and 1 and 2 months
      postoperatively. Specular microscope endothelial photography of the central
      region of the cornea was performed preoperatively and at 3 months after surgery.
      RESULTS: There were no significant differences among the bromfenac, betamethasone
      and combined treatment groups in BCVA, IOP, aqueous flare or corneal thickness.
      Cystoid macular oedema was present in one eye treated with betamethasone.
      CONCLUSIONS: There were no significant differences in anti-inflammatory effects
      among the three treatments. These findings suggest that bromfenac is as effective
      as betamethasone in minimizing inflammatory reactions after cataract surgery.

PMID- 19183414
TI  - Depressive relapse during lithium treatment associated with increased serum
      thyroid-stimulating hormone: results from two placebo-controlled bipolar I
      maintenance studies.
AB  - OBJECTIVE: To assess the relationship between depressive relapse and change in
      thyroid function in an exploratory post hoc analysis from a controlled
      maintenance evaluation of bipolar I disorder. METHOD: Mean thyroid-stimulating
      hormone (TSH) and outcome data were pooled from two 18-month, double-blind,
      placebo-controlled, maintenance studies of lamotrigine and lithium monotherapy. A
      post hoc analysis of 109 subjects (n = 55 lamotrigine, n = 32 lithium, n = 22
      placebo) with serum TSH values at screening and either week 52 (+/-14 days) or
      study drop-out was conducted. RESULTS: Lithium-treated subjects who required an
      intervention for a depressive episode had a significantly higher adjusted mean
      TSH level (4.4 microIU/ml) compared with lithium-treated subjects who did not
      require intervention for a depressive episode (2.4 microIU/ml). CONCLUSION:
      Lithium-related changes in thyroid function are clinically relevant and should be
      carefully monitored in the maintenance phase of bipolar disorder to maximize mood
      stability and minimize the risk of subsyndromal or syndromal depressive relapse.

PMID- 19183415
TI  - Low-fat oxidation may be a factor in obesity among men with schizophrenia.
AB  - OBJECTIVE: Obesity associated with atypical antipsychotic medications is an
      important clinical issue for people with schizophrenia. The purpose of this
      project was to determine whether there were any differences in resting energy
      expenditure (REE) and respiratory quotient (RQ) between men with schizophrenia
      and controls. METHOD: Thirty-one men with schizophrenia were individually matched
      for age and relative body weight with healthy, sedentary controls. Deuterium
      dilution was used to determine total body water and subsequently fat-free mass
      (FFM). Indirect calorimetry using a Deltatrac metabolic cart was used to
      determine REE and RQ. RESULTS: When corrected for FFM, there was no significant
      difference in REE between the groups. However, fasting RQ was significantly
      higher in the men with schizophrenia than the controls. CONCLUSION: Men with
      schizophrenia oxidised proportionally less fat and more carbohydrate under
      resting conditions than healthy controls. These differences in substrate
      utilisation at rest may be an important consideration in obesity in this clinical
      group.

PMID- 19183416
TI  - Standardization of allergen products: 1. Detailed characterization of GMP
      produced recombinant Bet v 1.0101 as biological reference preparation.
AB  - BACKGROUND: Standardization of allergen extracts requires the availability of
      well-characterized recombinant allergens, which can be used as reference
      standards provided by the European regulatory authorities. The objective of this
      study was the detailed physicochemical and immunological characterization of rBet
      v 1.0101, which shall be used in a ring trial within the framework of the
      Biological Standardization Programme BSP090 of the European Directorate for
      Quality of Medicines and Healthcare. METHODS: Recombinant Bet v 1.0101 Y0487 was
      produced under good manufacturing practice conditions and analysed by an array of
      physicochemical and immunological methods for identity, quantity, homogeneity,
      folding and denaturation, aggregation state and stability in solution, as well as
      biological activity. RESULTS: Batch Y0487 was shown to contain monomeric and well
      folded protein being identical with rBet v 1.0101, as determined by mass
      spectrometry. SDS-PAGE, isoelectric focusing, deamidation analysis and size
      exclusion chromatography with light scattering revealed sample homogeneity of
      >99.9%. Upon storage at +4 degrees C batch Y0487 retained the monomeric state up
      to 3 months. Protein quantification determined by amino acid analysis was found
      coinciding with half-maximal inhibition of serum IgE in ELISA. Biological
      activity of batch Y0487 was shown to be comparable to natural Bet v 1 by IgG and
      IgE immunoblotting, as well as basophil and T-cell activation. CONCLUSION:
      Recombinant Bet v 1.0101 Y0487 was characterized extensively by physicochemical
      and immunological methods. It was shown highly stable, monomeric and
      immunologically equivalent to its natural counterpart. Thus, it represents an
      appropriate candidate reference standard for Bet v 1.

PMID- 19183417
TI  - Prolonged antigen-exposure with carbohydrate particle based vaccination prevents
      allergic immune responses in sensitized mice.
AB  - BACKGROUND: Defined particles carrying tightly bound allergens at high density
      have been suggested as alternatives in allergy vaccination. Carbohydrate based
      particles (CBP), sized 2 microm, provide a platform for covalent coupling of
      allergens. OBJECTIVE: To investigate the mechanisms of antigen presentation by
      CBP, as well as cellular and humoral responses after vaccination with the major
      cat allergen Fel d 1, covalently coupled to CBP. METHODS: Mice (n = 10/group)
      were subcutaneously vaccinated with CBP-rFel d 1, CBP or phosphate buffer saline
      (PBS) before sensitization with rFel d 1 and challenged with cat dander extract.
      Fluorescent and (75)Se-radiolabeled tracking of allergens and particles were
      performed with flow cytometry and whole-body autoradiography. Humoral, cellular
      and regulatory immune responses were analyzed by ELISA and flow cytometry.
      Cytokines were measured in bronchoalveolar lavage fluid and splenocyte cultures.
      RESULTS: CBP-rFel d 1 prevented induction of airway inflammation and induced
      allergen-specific T-cell anergy. CBP-rFel d 1 also induced rapid IgM and IgG1
      responses compared with soluble rFel d 1. Particles were phagocytosed by antigen
      presenting cells and transported to draining lymph nodes and spleen. Moreover,
      antigen coupled to CBP remained longer at the injection site compared with alum.
      CONCLUSIONS: Covalent coupling of rFel d 1 to CBP induces rapid antibody
      production, prevents induction of allergic immune responses and systemic allergen
      spreading. Thus, CBP comprise several attractive adjuvant features for use in
      allergy vaccination. CLINICAL IMPLICATIONS: Prolonged allergen exposure through
      covalent coupling to particles suitable for phagocytosis, provides an adjuvant
      for safer and efficient allergy vaccination.

PMID- 19183418
TI  - Prevalence and risk factors for allergic contact dermatitis to topical treatment
      in atopic dermatitis: a study in 641 children.
AB  - BACKGROUND: There is little information regarding the risk of sensitization
      associated with topical atopic dermatitis (AD) treatment. OBJECTIVES: To assess
      the frequency of sensitization to topical treatment of AD in children and to
      determine risk factors associated with skin sensitization. METHODS: Six hundred
      and forty-one children with AD were systematically patch tested with seven agents
      of common topical treatment: chlorhexidine, hexamidine, budesonide, tixocortol
      pivalate, bufexamac, sodium fusidate and with the current emollient used by the
      child. The following variables were recorded: age, sex, age at onset of AD,
      associated asthma, severity of AD, and history of previous exposure to topical
      agents used in the treatment of AD. Skin prick tests to inhalant and food
      allergens were used to explore the IgE-mediated sensitization. RESULTS: Forty-one
      positive patch tests were found in 40 patients (6.2%). Allergens were emollients
      (47.5%), chlorhexidine (42.5%), hexamidine (7.5%), tixocortol pivalate and
      bufexamac (2.5% each). Risk factors associated with sensitization to AD treatment
      were AD severity [OR: 3.3; 95% confidence interval (CI):1.5-7.1 for moderate to
      severe AD], AD onset before the age of 6 months (OR: 2.7; 95% CI: 1.2-6.1), and
      IgE-mediated sensitization (OR: 2.5; 95% CI: 1.1-5.9). CONCLUSIONS: Topical
      treatment of AD is associated with cutaneous sensitization. Antiseptics and
      emollients represent the most frequent sensitizers and may be included in the
      standard series in AD children when contact dermatitis is suspected. Risk factors
      associated with sensitization to AD topical treatments are AD severity, early AD
      onset and IgE-mediated sensitization.

PMID- 19183419
TI  - An economic evaluation of NIOX MINO airway inflammation monitor in the United
      Kingdom.
AB  - BACKGROUND: Fractional exhaled nitric oxide (FENO), a marker of eosinophilic
      airway inflammation, is easily measured by noninvasive means. The objective of
      this study was to determine the cost-effectiveness of FENO measurement using a
      hand-held monitor (NIOX MINO), at a reimbursement price of 23 pound sterling, for
      asthma diagnosis and management in the UK. METHODS: We constructed two decision
      trees to compare FENO measurement with standard diagnostic testing and guideline
      recommendations for management. For asthma diagnosis, we compared FENO
      measurement with lung function and reversibility testing, bronchial provocation
      and sputum eosinophil count. For asthma management, we evaluated the impact on
      asthma control, including inhaled corticosteroid use, exacerbations and
      hospitalizations, of monitoring with FENO measurement vs symptoms and lung
      function as in standard care. Resource use and health outcomes were evaluated
      over a 1-year time frame. Direct costs were calculated from a UK health-care
      payer perspective (2005 pound sterling). RESULTS: An asthma diagnosis using FENO
      measurement cost 43 pound sterling less per patient as compared with standard
      diagnostic tests. Asthma management using FENO measurement instead of lung
      function testing resulted in annual cost-savings of 341 pound sterling and 0.06
      quality-adjusted life-years gained for patients with mild to severe asthma and
      cost-savings of 554 pound sterling and 0.004 quality-adjusted life-years gained
      for those with moderate to severe asthma. CONCLUSIONS: Asthma diagnosis based on
      FENO measurement with NIOX MINO alone is less costly and more accurate than
      standard diagnostic methods. Asthma management based on FENO measurement is less
      costly than asthma management based on standard guidelines and provides similar
      health benefits.

PMID- 19183420
TI  - The relationship between sleep duration and obesity in Turkish children and
      adolescents.
AB  - AIM: To determine the relationship between sleep duration and obesity in Turkish
      children and adolescents. METHODS: This study was conducted in Turkey with 5358
      children aged 6 to 17 years. Height, weight, waist circumference (WC), mid-upper
      arm circumference (MUAC), triceps skinfold thickness were measured. Body mass
      index (BMI), arm fat area were calculated. Self-reported sleep duration by
      parents were obtained. RESULTS: As sleep duration increased, BMI, which was
      significantly higher in girls sleeping < or =8 h, decreased (p < 0.05). WC, MUAC,
      BMI were significantly higher in boys sleeping < or =8 h versus males sleeping >
      or =10 h. Boys sleeping < or =10 h in 6.0-17.0-years had significantly higher
      risk of overweight/obesity. In 6.0 to 17.0 years, the risk of overweight/obesity
      in boys sleeping 9-10 h, 8-9 h and < or =8 h were 1.86-, 1.74- and 2.06-times
      higher respectively, versus children sleeping > or =10 h (p < 0.05). CONCLUSION:
      Sleep duration may be an important factor for obesity and providing > or =10 h of
      sleep is recommended as a prevention strategy for obesity.

PMID- 19183422
TI  - Effect of transdermal botulinum toxin on sweat secretion in subjects with
      idiopathic palmar hyperhidrosis.

PMID- 19183423
TI  - Every cloud has a silver lining?

PMID- 19183424
TI  - Illness perceptions, coping and quality of life in patients with alopecia.
AB  - BACKGROUND: Alopecia can have substantial psychological consequences, but there
      has been no research looking at patients' beliefs about their condition nor how
      they relate to quality of life (QoL). OBJECTIVES: To investigate the
      relationships between illness perceptions, coping and QoL in patients with
      alopecia. METHODS: The study employed a cross-sectional design. In total, 214
      individuals with alopecia were recruited from four internet support groups. There
      were 171 women and 43 men (mean age 35 years). Participants completed an online
      questionnaire comprising the Revised Illness Perception Questionnaire, the
      Dermatology Life Quality Index and the brief COPE. RESULTS: The findings indicate
      several areas in which alopecia impacted on individuals' QoL, particularly in
      relation to symptoms and feelings. Women reported poorer QoL compared with men.
      Impaired QoL was associated with a strong illness identity, beliefs in the
      serious consequences of alopecia and strong emotional representations.
      Hierarchical multiple regressions indicated that illness perceptions accounted
      for 35% of the variance in QoL after controlling for demographic and disease
      factors, with coping adding a further 7% to the regression model. CONCLUSIONS:
      Although alopecia is not a life-threatening condition, it can impair QoL by
      negatively impacting on self-awareness. The strong relationships found between
      patients' beliefs about their condition and QoL suggests that health
      professionals should recognize the psychological impact of alopecia and address
      negative beliefs and emotions surrounding the condition in treatment programmes.

PMID- 19183425
TI  - Interferon-induced versus chemokine transcripts as lupus biomarkers.
AB  - Compelling support for a central role for interferon-alpha in lupus pathogenesis
      has led to a new focus on the role of innate immune system activation in the
      generation of pathogenic mediators. These insights have been extended in
      translational studies of patients with well-characterized disease activity and
      clinical manifestations in order to identify informative molecular biomarkers.
      Chemokines are among the interferon-inducible genes, and new data support an
      association between the expression of chemokines and both lupus disease activity
      and organ damage. Longitudinal studies that relate molecular biomarkers to
      disease activity will be needed to validate these promising data and establish a
      sensitive measure of change for interventional studies and patient care.

PMID- 19183426
TI  - Limb regeneration revisited.
AB  - The investigation of vertebrate limb regeneration, a favorite topic of early
      developmental biologists, is enjoying a renaissance thanks to recently developed
      molecular and genetic tools, as indicated in recent papers in BMC Biology and BMC
      Developmental Biology. Classical experiments provide a rich context for
      interpreting modern functional studies.

PMID- 19183427
TI  - ICU staffing and patient outcomes: more work remains.
AB  - Many studies have demonstrated that closed intensive care units (ICUs), staffed
      by trained intensivists, are associated with improved patient outcomes. However,
      the mechanisms by which ICU organizational factors, such as physician staffing,
      influence patient outcomes are unclear. One potential mechanism is the increased
      utilization of evidence-based practices in closed ICUs. Cooke and colleagues
      investigated this hypothesis in a cohort of 759 acute lung injury patients in 23
      ICUs in King County, Washington, USA. Although closed ICUs were independently
      associated with a modestly lower mean tidal volume, this finding did not explain
      the mortality benefit associated with a closed ICU model in this patient cohort.
      Future studies should evaluate other potential mechanisms by which closed ICUs
      improve patient outcomes. An improved understanding of these mechanisms may yield
      new targets for improving the quality of medical care for all ICU patients.

PMID- 19183428
TI  - Ingredients for adequate evaluation of blood glucose algorithms as applied to the
      critically ill.
AB  - The article by Eslami and colleagues provides an overview of the indicators used
      to measure the quality of blood glucose control in patients admitted to the
      intensive care unit. Each indicator can be related to one or more of the
      following categories: blood glucose zones, blood glucose levels, time intervals,
      and features of the insulin titration algorithm. Some important issues (for
      instance those concerning the clarity of definitions used for glycaemic
      thresholds) are raised. This systematic review calls for a practical guide to
      advise the clinician how different blood glucose signals should (ideally) be
      evaluated and which steps should to be undertaken.

PMID- 19183429
TI  - Understanding the cognitive consequences of critical illness through experimental
      animal models.
AB  - Tuon and colleagues have developed an animal model to examine the impact of
      sepsis on memory in rats. They report important data that expand the
      understanding of the cognitive consequences of critical illness. Future research
      should follow this path of inquiry and extend animal models beyond aversive
      conditioning to include recently developed paradigms that will permit assessment
      of complex and cognitive processes, such as attention, episodic memory and
      orientation to time and place. This has the potential to greatly increase the
      putative understanding of the homologous neurocognitive dysfunctions acquired
      during critical illness.

PMID- 19183430
TI  - Hypothalamo-pituitary-adrenal axis activity after intracranial catastrophies:
      what is enough?
AB  - This commentary on a paper by Bendel and colleagues in the previous issue of
      Critical Care describes the difficulty in assessing the sufficiency of adrenal
      responses to endogenous, stress-induced adrenocorticotropic hormone (ACTH)
      release by the pituitary or to exogenous ACTH administration in the critically
      ill patient in general, and after subarachnoid hemorrhage in particular. It is
      argued that comparisons with responses under circumstances of equal stress as
      well as assessments of severity of disease are necessary to judge the sufficiency
      of cortisol responses to endogenous and exogenous ACTH before treatment is
      considered. There are no universally applicable cutoff values for cortisol levels
      -and increases in cortisol levels with increasing levels of ACTH--for the
      diagnosis of relative adrenal insufficiency (or as it is now commonly termed,
      critical illnes-related corticosteroid insufficiency) following, for example,
      subarachnoid hemorrhage or other intracranial catastrophes. The paper by Bendel
      and colleagues is critically discussed in view of these concepts.

PMID- 19183431
TI  - Bench-to-bedside review: the importance of the precision of the reference
      technique in method comparison studies--with specific reference to the
      measurement of cardiac output.
AB  - Bland-Altman analysis is used for assessing agreement between two measurements of
      the same clinical variable. In the field of cardiac output monitoring, its
      results, in terms of bias and limits of agreement, are often difficult to
      interpret, leading clinicians to use a cutoff of 30% in the percentage error in
      order to decide whether a new technique may be considered a good alternative.
      This percentage error of +/- 30% arises from the assumption that the commonly
      used reference technique, intermittent thermodilution, has a precision of +/- 20%
      or less. The combination of two precisions of +/- 20% equates to a total error of
      +/- 28.3%, which is commonly rounded up to +/- 30%. Thus, finding a percentage
      error of less than +/- 30% should equate to the new tested technique having an
      error similar to the reference, which therefore should be acceptable. In a worked
      example in this paper, we discuss the limitations of this approach, in particular
      in regard to the situation in which the reference technique may be either more or
      less precise than would normally be expected. This can lead to inappropriate
      conclusions being drawn from data acquired in validation studies of new
      monitoring technologies. We conclude that it is not acceptable to present
      comparison studies quoting percentage error as an acceptability criteria without
      reporting the precision of the reference technique.

PMID- 19183432
TI  - Clinical information systems in the intensive care unit: primum non nocere.
AB  - Information and communication technology has the potential to address many
      problems encountered in intensive care unit (ICU) care, namely managing large
      amounts of patient and research data and reducing medical errors. The paper by
      Morrison and colleagues in the previous issue of Critical Care describes the
      adverse impact of introducing an electronic patient record in the ICU on multi
      disciplinary communication during ward rounds. The importance of evaluation and
      technology assessment in the implementation and use of new computing technology
      is highlighted.

PMID- 19183433
TI  - What do biomarkers tell us about the pathogenesis of ankylosing spondylitis?
AB  - Biomarkers may provide information that promotes understanding of prognosis,
      disease activity, and pathogenesis in ankylosing spondylitis. Biomarkers
      reflecting disease activity (metallo-proteinase-3) and inflammatory lesions on
      magnetic resonance imaging predict new bone formation and are ameliorated by anti
      tumor necrosis factor therapy, yet this treatment may not prevent new bone
      formation. Moreover, elevated levels of biomarkers reflecting tissue repair (bone
      specific alkaline phosphatase) post-treatment together with magnetic resonance
      imaging indicates such treatment may even promote repair through new bone
      formation. Tumor necrosis factor regulation of Dickkopf-1 may constitute a
      molecular brake that controls osteoblastogenesis through wingless and bone
      morphogenetic proteins in an established inflammatory lesion in ankylosing
      spondylitis.

PMID- 19183434
TI  - The genetics of acute lung injury: looking back and pointing the way forward.
AB  - Individual genetic factors have long been suspected of playing a major role in
      susceptibility to acute lung injury and acute respiratory distress syndrome.
      Flores and colleagues evaluate the quality of published studies testing the
      relationships between variation in candidate genes and susceptibility to lung
      injury syndromes or worsened outcome in patients with these conditions. Their
      results demonstrate that while important advances have been made in this area,
      attention should be paid to improving the methodology of future studies in order
      to minimize the chances of publishing false-positive results.

PMID- 19183435
TI  - Natriuretic peptide determinations in critical care medicine: part of routine
      clinical practice or research test only?
AB  - Measurement of N-terminal pro-B-type natriuretic peptide has been shown a good
      rule-out test for cardiac dysfunction in patients in the intensive care unit. The
      peptide measurement should not be used as a replacement for other forms of
      monitoring, and performs best as a diagnostic test when interpreted together with
      other clinical findings and investigations. At a cutoff value similar to that
      found in other clinical studies in acute decompensated heart failure, measurement
      of N-terminal pro-B-type natriuretic peptide offers an additional tool for
      diagnostic assessment of patients presenting to the intensive care physician.

PMID- 19183436
TI  - Increased PADI4 expression in blood and tissues of patients with malignant
      tumors.
AB  - BACKGROUND: Peptidylarginine deiminase type 4 (PAD4/PADI4) post-translationally
      converts peptidylarginine to citrulline. Recent studies suggest that PADI4
      represses expression of p53-regulated genes via citrullination of histones at
      gene promoters. METHODS: Expression of PADI4 was investigated in various tumors
      and non-tumor tissues (n = 1673) as well as in A549, SKOV3 and U937 tumor cell
      lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4
      and citrullinated antithrombin (cAT) were investigated in the blood of patients
      with various tumors by ELISA (n = 1121). RESULTS: Immunohistochemistry detected
      significant PADI4 expression in various malignancies including breast carcinomas,
      lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer
      cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas,
      endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas,
      as well as other metastatic carcinomas. However, PADI4 expression was not
      observed in benign leiomyomas of stomach, uterine myomas, endometrial
      hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell
      hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas,
      neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally,
      PADI4 expression was not detected in non-tumor tissues including cholecystitis,
      cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed
      tissues such as in gastritis and appendicitis. Quantitative PCR and western blot
      analysis showed higher PADI4 expression in gastric adenocarcinomas, lung
      adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and
      breast cancers (n = 5 for each disease) than in the surrounding healthy tissues.
      Furthermore, western blot analysis detected PADI4 expression in cultured tumor
      cell lines. ELISA detected increased PADI4 and cAT levels in the blood of
      patients with various malignant tumors compared to those in patients with chronic
      inflammation and benign tumors. This was consistent with immunohistochemical
      results. Additionally, PADI4 and cAT levels were significantly associated with
      higher levels of known tumor markers. CONCLUSION: Our results suggest that PADI4
      expression is increased in the blood and tissues of many malignant tumors, a
      finding useful for further understanding of tumorigenesis.

PMID- 19183437
TI  - STAMP: Extensions to the STADEN sequence analysis package for high throughput
      interactive microsatellite marker design.
AB  - BACKGROUND: Microsatellites (MSs) are DNA markers with high analytical power,
      which are widely used in population genetics, genetic mapping, and forensic
      studies. Currently available software solutions for high-throughput MS design (i)
      have shortcomings in detecting and distinguishing imperfect and perfect MSs, (ii)
      lack often necessary interactive design steps, and (iii) do not allow for the
      development of primers for multiplex amplifications. We present a set of new
      tools implemented as extensions to the STADEN package, which provides the
      backbone functionality for flexible sequence analysis workflows. The possibility
      to assemble overlapping reads into unique contigs (provided by the base
      functionality of the STADEN package) is important to avoid developing redundant
      markers, a feature missing from most other similar tools. RESULTS: Our extensions
      to the STADEN package provide the following functionality to facilitate
      microsatellite (and also minisatellite) marker design: The new modules (i)
      integrate the state-of-the-art tandem repeat detection and analysis software
      PHOBOS into workflows, (ii) provide two separate repeat detection steps - with
      different search criteria - one for masking repetitive regions during assembly of
      sequencing reads and the other for designing repeat-flanking primers for MS
      candidate loci, (iii) incorporate the widely used primer design program PRIMER3
      into STADEN workflows, enabling the interactive design and visualization of
      flanking primers for microsatellites, and (iv) provide the functionality to find
      optimal locus- and primer pair combinations for multiplex primer design.
      Furthermore, our extensions include a module for storing analysis results in an
      SQLite database, providing a transparent solution for data access from within as
      well as from outside of the STADEN Package. CONCLUSION: The STADEN package is
      enhanced by our modules into a highly flexible, high-throughput, interactive tool
      for conventional and multiplex microsatellite marker design. It gives the user
      detailed control over the workflow, enabling flexible combinations of manual and
      automated analysis steps. The software is available under the OpenBSD License 12.
      The high efficiency of our automated marker design workflow has been confirmed in
      three microsatellite development projects.

PMID- 19183438
TI  - Lossless filter for multiple repeats with bounded edit distance.
AB  - BACKGROUND: Identifying local similarity between two or more sequences, or
      identifying repeats occurring at least twice in a sequence, is an essential part
      in the analysis of biological sequences and of their phylogenetic relationship.
      Finding such fragments while allowing for a certain number of insertions,
      deletions, and substitutions, is however known to be a computationally expensive
      task, and consequently exact methods can usually not be applied in practice.
      RESULTS: The filter TUIUIU that we introduce in this paper provides a possible
      solution to this problem. It can be used as a preprocessing step to any multiple
      alignment or repeats inference method, eliminating a possibly large fraction of
      the input that is guaranteed not to contain any approximate repeat. It consists
      in the verification of several strong necessary conditions that can be checked in
      a fast way. We implemented three versions of the filter. The first is simply a
      straightforward extension to the case of multiple sequences of an application of
      conditions already existing in the literature. The second uses a stronger
      condition which, as our results show, enable to filter sensibly more with
      negligible (if any) additional time. The third version uses an additional
      condition and pushes the sensibility of the filter even further with a non
      negligible additional time in many circumstances; our experiments show that it is
      particularly useful with large error rates. The latter version was applied as a
      preprocessing of a multiple alignment tool, obtaining an overall time (filter
      plus alignment) on average 63 and at best 530 times smaller than before (direct
      alignment), with in most cases a better quality alignment. CONCLUSION: To the
      best of our knowledge, TUIUIU is the first filter designed for multiple repeats
      and for dealing with error rates greater than 10% of the repeats length.

PMID- 19183439
TI  - Multimodal stone therapy for two forgotten and encrusted ureteral stents: a case
      report.
AB  - INTRODUCTION: Ureteral stent placement is a common procedure in daily urologic
      practice. To manage the problems of forgotten stents for many years needs
      multimodal stone therapy. CASE PRESENTATION: We present a case of a 26-years-old
      Caucasian, white woman with two forgotten encrusted ureteral stents for 48
      months. Multimodal stone therapy including extracorporeal shock wave (SWL),
      percutaneous nephrolithotomy (PCNL), ureterorenoscopy (URS), cystolithotripsy
      with Lithoclast, and open surgery was necessary to remove all the stones. Using
      the described combination of techniques, our patient was rendered stone and stent
      free. Urologists should bear in mind the presence of severe encrustations when
      they have to deal with a forgotten stent. CONCLUSION: This case shows that
      combined urologic techniques can achieve successful and safe management of
      forgotten stents, but treatment should be tailored to the volume of encrustation
      and associated stone.

PMID- 19183440
TI  - Burden of disease due to cancer in Spain.
AB  - BACKGROUND: Burden of disease is a joint measure of mortality and morbidity which
      makes it easier to compare health problems in which these two components enjoy
      different degrees of relative importance. The objective of this study is
      ascertaining the burden of disease due to cancer in Spain via the calculation of
      disability-adjusted life years (DALYs). METHODS: DALYs are the sum of years of
      life lost due to premature mortality and years lost due to disability. World
      Health Organization methodology and the following sources of data were used: the
      Mortality Register and Princeton Model Life Table for Years of life lost due to
      premature mortality and population, incidence estimates (Spanish tumour
      registries and fitting of generalized linear mixed models), duration (from data
      of survival in Spain from the EUROCARE-3 study and fitting of Weibull
      distribution function) and disability (weights published in the literature) for
      Years lost due to disability. RESULTS: There were 828,997 DALYs due to cancer
      (20.5 DALYs/1,000 population), 61% in men. Of the total, 51% corresponded to
      lung, colorectal, breast, stomach and prostate cancers. Mortality (84% of DALYs)
      predominated over disability. Subjects aged under 20 years accounted for 1.6% and
      those aged over 70 years accounted for 30.1% of DALYs. CONCLUSION: Lung,
      colorectal and breast cancers are responsible for the highest number of DALYs in
      Spain. Even if the burden of disease due to cancer is predominantly caused by
      mortality, some cancers have a significant weight of disability. Information on
      2000 burden of disease due to cancer can be useful to assess how it has evolved
      over time and the impact of medical advances on it in terms of mortality and
      disability.

PMID- 19183441
TI  - Two-dimensional power Doppler-three-dimensional ultrasound imaging of a cesarean
      section dehiscence with utero-peritoneal fistula: a case report.
AB  - INTRODUCTION: An imaging diagnosis after an iterative cesarean delivery is
      reviewed demonstrating a fine ultrasound-pathologic correlation. CASE
      PRESENTATION: A 33-year-old woman (G3, P3) presented referring intense
      dysmenorrhea and intermenstrual spotting since her third cesarean delivery, 1
      year before. A cesarean section dehiscence with utero-peritoneal fistula was
      diagnosed by transvaginal ultrasound. CONCLUSION: We can conclude that
      transvaginal two-dimensional power Doppler and three-dimensional ultrasound are
      highly accurate in detecting cesarean section dehiscence and uterine fistula.

PMID- 19183442
TI  - Does television viewing predict dietary intake five years later in high school
      students and young adults?
AB  - BACKGROUND: Prior research has found that television viewing is associated with
      poor diet quality, though little is known about its long-term impact on diet,
      particularly during adolescence. This study examined the associations between
      television viewing behavior with dietary intake five years later. METHODS: Survey
      data, which included television viewing time and food frequency questionnaires,
      were analyzed for 564 middle school students (younger cohort) and 1366 high
      school students (older cohort) who had complete data available at Time 1 (1998
      1999) and five years later at Time 2 (mean age at Time 2, 17.2 +/- 0.6 and 20.5
      +/- 0.8 years, respectively). Regression models examined longitudinal
      associations between Time 1 television viewing behavior and Time 2 dietary intake
      adjusting for sociodemographic characteristics, Time 1 dietary intake, and Time 2
      total daily energy intake. RESULTS: Respondents were categorized as limited
      television users (<2 hours/daily), moderately high television viewers (2-5
      hours/daily), and heavy television viewers (>/=5 hours/daily). Among the younger
      cohort, Time 1 heavy television viewers reported lower fruit intake and higher
      sugar-sweetened beverage consumption than the other two groups. Among the older
      cohort, watching five or more hours of television per day at Time 1, predicted
      lower intakes of fruits, vegetables, whole grain and calcium-rich foods, and
      higher intakes of trans fat, fried foods, fast food menu items, snack products,
      and sugar-sweetened beverages (products commonly advertised on television) five
      years later. CONCLUSION: Television viewing in middle and high school predicted
      poorer dietary intake five years later. Adolescents are primary targets of
      advertising for fast food restaurants, snack foods, and sugar-sweetened
      beverages, which may influence their food choices. Television viewing, especially
      during high school, may have long-term effects on eating choices and contribute
      to poor eating habits in young adulthood.

PMID- 19183443
TI  - The strategic targeting of females by transnational tobacco companies in South
      Korea following trade liberalization.
AB  - BACKGROUND: In 1988 South Korea opened its cigarette market to foreign companies
      under the threat of US trade sanctions. Despite strong social stigma against
      female smoking in South Korea, and restrictions on tobacco marketing to women and
      children, smoking rates among young Korean females increased from 1.6% in 1988 to
      13% in 1998. Previous analyses describe how Asian countries have been targeted by
      transnational tobacco companies for new markets, with Asian females offering
      substantial future growth potential. An understanding of the strategies used by
      TTCs to increase smoking among Korean females is critical to public health
      efforts to adopt a stronger gender perspective in implementing the Framework
      Convention on Tobacco Control. METHODS: Internal documents of transnational
      tobacco corporations were systematically searched using keywords focused on the
      targeting of the female market since market liberalization in 1988. Industry
      documents were analysed alongside primary and secondary data on the tobacco
      industry in South Korea. RESULTS: TTCs have targeted Korean females since the
      late 1980s, conducting market research to understand consumer preferences,
      cultural characteristics and social changes affecting women and girls. Brands
      designed to appeal to females have focused on "slim" and "superslim" cigarettes,
      "light" and "mild" claims, and marketing which appeals to the growing numbers of
      young women entering the labour force. Strategies for overcoming legal
      restrictions on marketing to women and children have included the use of company
      rather than brand names, retail distribution at venues frequented by females,
      trademark diversification and sponsorship. CONCLUSION: Given the high male
      smoking rates in South Korea, tobacco control efforts have given limited
      attention to girls and women. The limited data available on female smoking
      behaviour suggests that, despite legal restrictions and social stigma, smoking
      among females has increased since market opening, notably within younger age
      groups. In addition to more detailed trend data, there is an urgent need for the
      development and implementation of gender-sensitive tobacco control measures. Part
      of South Korea's accession to the FCTC should include emphasis on measures to
      address the strategic targeting of Korean females by TTCs.

PMID- 19183444
TI  - Regional and social differences concerning overweight, participation in health
      check-ups and vaccination. Analysis of data from a whole birth cohort of 6-year
      old children in a prosperous German city.
AB  - BACKGROUND: Studies on health inequalities still focus mostly on adults. Research
      about social disparities and health in children is slowly increasing, also in
      Germany, but these studies are mostly restricted to individual social variables
      derived from the parents to determine social class. This paper analyses the data
      of the medical check-up prior to school enrolment to determine differences
      concerning overweight, participation in health check-ups and immunization; it
      includes individual social variables but also regional variables describing the
      social environment of the children. METHODS: The dataset includes 9,353 children
      who started school in 2004 in Munich, Germany. Three dependent variables are
      included (i.e. overweight, health check-ups, vaccinations). The individual level
      social variables are: children's sex, mother tongue of the parents, Kindergarten
      visit. On the small scale school district level, two regional social variables
      could be included as well, i.e. percentage of single-parent households,
      percentage of households with low educational level. Associations are assessed by
      cross tables and regression analyses. The regional level variables are included
      by multilevel analyses. RESULTS: The analyses indicate that there is a large
      variation between the school districts concerning the three dependent variables,
      and that there is no district with very 'problematic values' for all three of
      them (i.e. high percentage of overweight, low levels of health check-ups and
      vaccinations). Throughout the bivariate and multivariate analyses, the mother
      tongue of the children's parents shows the most pronounced association with these
      dependent variables; i.e. children growing up in non-German-speaking families
      tend to be more overweight and don't visit preventive check-ups as often as
      children of German-speaking parents. An opposite association can be seen
      concerning vaccinations. Regional level influences are present as well, but they
      are rather small when the individual level social variables are controlled for.
      CONCLUSION: The dataset of the medical check-up prior to school enrolment offers
      a great opportunity for public health research, as it comprises a whole age
      cohort. The number and scope of variables is quite limited, though. On one hand,
      it includes only few variables on health or health related risks. On the other,
      it would be important to have more information from the region where the children
      live, e.g. the availability of community and health care services for parents and
      children, social networks of families with children, areas where children can
      play outside, traffic noise and air pollution. Despite these shortcomings, the
      need for specific interventions can already be derived from the data analyzed
      here, e.g. programs to reduce overweight in children should focus on parents with
      a mother tongue other than German.

PMID- 19183445
TI  - Ahmedabad tolerance induction protocol and chronic renal allograft dysfunction:
      pathologic observations and clinical implications.
AB  - BACKGROUND: Chronic Renal Allograft Dysfunction (CRAD) is responsible for a large
      number of graft failures. We have abrogated acute T-cell rejections using
      Ahmedabad Tolerance Induction Protocol (ATIP) with hematopoietic stem cell
      transplantation (HSCT) under non-myeloablative conditioning pre-transplant.
      However B-cell mediated rejections and CRAD continue to haunt us. We carried out
      retrospective analysis of renal allograft biopsies performed in the last 4 years
      to evaluate the effect of ATIP on CRAD. MATERIALS AND METHODS: Biopsies diagnosed
      as per modified Banff criteria belonged to 2 groups: ATIP under low dose
      immunosuppression of cyclosporine/Azathioprine/Mycofenolate mofetil+
      Prednisolone, subjected to donor leucocyte transfusion, anti-T/B cell antibodies,
      low dose target specific irradiation, cyclophosphamide, cyclosporin followed by
      HSCT pre-transplant; controls who opted out of ATIP were transplanted under
      standard triple drug immunosuppression. Demographics of both groups were
      comparable. RESULTS: Incidence of chronic changes was higher in controls (17.5%)
      vs. 10.98% in ATIP over a mean follow up of 151.9 months in the former and 130.9
      months in the latter. Proteinuria and hypertension were higher in controls
      (48.4%) vs. ATIP (32.7%) with chronic transplant glomerulopathy, focal global
      sclerosis in 67.7% in controls vs. 46.7% in ATIP, acute on chronic T/B cell
      rejection in 51.6% controls vs. 28.1% ATIP, with peritubular capillary C4d
      deposits in 19.4% controls vs. 1.9% ATIP biopsies. Acute on chronic calcineurin
      inhibitor toxicity was higher in ATIP (71.9%) vs. 48.4% in controls. CONCLUSION:
      Chronic immune injury was less with ATIP vs controls as compared to a higher
      incidence of chronic calcineurin inhibitor toxicity in the former.

PMID- 19183446
TI  - Early onset lactating adenoma and the role of breast MRI: a case report.
AB  - INTRODUCTION: Lactating adenoma is a benign condition, representing the most
      prevalent breast lesion in pregnant women and during puerperium; in this paper, a
      case of a woman with lactating adenoma occurring during the first trimester of
      pregnancy is reported. There have been no reports in the literature, according to
      our search, focusing on magnetic resonance imaging findings in cases of lactating
      adenomas. Also the early onset of the lesion during the first trimester of
      pregnancy is quite unusual and possibly unique. CASE PRESENTATION: We report the
      case of a primiparous 30-year-old Caucasian woman, who noted an asymptomatic lump
      within her left breast during the 9th week of gestation, slightly increasing in
      size over the next few weeks. Ultrasound demonstrated a hypoecoic solid mass,
      hypervascularized and measuring 4 cm. On magnetic resonance imaging, performed in
      the first month after delivery, the lesion appeared as an ovoidal homogeneous
      mass, with regular margins and a significant contrast enhancement indicative of a
      giant adenoma. CONCLUSION: Magnetic resonance imaging could play an important
      role in the differential diagnosis of pregnancy-related breast lumps,
      particularly during puerperium, thus avoiding unnecessary surgical biopsies.

PMID- 19183447
TI  - Human antimicrobial protein hCAP18/LL-37 promotes a metastatic phenotype in
      breast cancer.
AB  - INTRODUCTION: Human cathelicidin antimicrobial protein, hCAP18, and its C
      terminal peptide LL-37 is a multifunctional protein. In addition to being
      important in antimicrobial defense, it induces chemotaxis, stimulates
      angiogenesis and promotes tissue repair. We previously showed that human breast
      cancer cells express high amounts of hCAP18, and hypothesised that hCAP18/LL-37
      may be involved in tumour progression. METHODS: hCAP18 mRNA was quantified in 109
      primary breast cancers and compared with clinical findings and ERBB2 mRNA
      expression. Effects of exogenous LL-37 and transgenic overexpression of hCAP18 on
      ErbB2 signalling were investigated by immunoblotting using extracts from breast
      cancer cell lines ZR75-1 and derivatives of MCF7. We further analysed the impact
      of hCAP18/LL-37 on the morphology of breast cancer cells grown in soft agar, on
      cell migration and on tumour development in severe combined immunodeficiency
      (SCID) mice. RESULTS: The expression of hCAP18 correlated closely with that of
      ERBB2 and with the presence of lymph node metastases in oestrogen receptor
      positive tumours. hCAP18/LL-37 amplified Heregulin-induced mitogen-activated
      protein kinase (MAPK) signalling through ErbB2, identifying a functional
      association between hCAP18/LL-37 and ErbB2 in breast cancer. Treatment with LL-37
      peptide significantly stimulated the migration of breast cancer cells and their
      colonies acquired a dispersed morphology indicative of increased metastatic
      potential. A truncated version of LL-37 competitively inhibited LL-37 induced
      MAPK phosphorylation and significantly reduced the number of altered cancer cell
      colonies induced by LL-37 as well as suppressed their migration. Transgenic
      overexpression of hCAP18 in a low malignant breast cancer cell line promoted the
      development of metastases in SCID mice, and analysis of hCAP18 transgenic tumours
      showed enhanced activation of MAPK signalling. CONCLUSIONS: Our results provide
      evidence that hCAP18/LL-37 contributes to breast cancer metastasis.

PMID- 19183448
TI  - Identification of a potent herbal molecule for the treatment of breast cancer.
AB  - BACKGROUND: Breast cancer (BCa)-related mortality still remains the second
      leading cause of cancer-related deaths worldwide. Patients with BCa have
      increasingly shown resistance and high toxicity to current chemotherapeutic drugs
      for which identification of novel targeted therapies are required. METHODS: To
      determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER+)-MCF-7
      and estrogen-receptor negative (ER-)-MDA 231 cells were treated with PDBD and the
      cell viability, apoptotic, cell cycle, Western blot and Promoter assays were
      performed. RESULTS: PDBD inhibits cell viability of ER+ and ER- BCa cells by
      inducing apoptosis without causing significant toxicity in normal breast
      epithelial cells. While dissecting the mechanism of action of PDBD on BCa, we
      found that PDBD inhibits Akt signaling and its downstream targets such as NF
      kappaB activation, IAP proteins and Bcl-2 expression. On the other hand,
      activation of JNK/p38 MAPK-mediated pro-apoptotic signaling was observed in both
      ER+ and ER- BCa cells. CONCLUSION: These findings suggest that PDBD may have wide
      therapeutic application in the treatment of BCa.

PMID- 19183449
TI  - Universal features in the genome-level evolution of protein domains.
AB  - BACKGROUND: Protein domains can be used to study proteome evolution at a coarse
      scale. In particular, they are found on genomes with notable statistical
      distributions. It is known that the distribution of domains with a given topology
      follows a power law. We focus on a further aspect: these distributions, and the
      number of distinct topologies, follow collective trends, or scaling laws,
      depending on the total number of domains only, and not on genome-specific
      features. RESULTS: We present a stochastic duplication/innovation model, in the
      class of the so-called 'Chinese restaurant processes', that explains this
      observation with two universal parameters, representing a minimal number of
      domains and the relative weight of innovation to duplication. Furthermore, we
      study a model variant where new topologies are related to occurrence in genomic
      data, accounting for fold specificity. CONCLUSIONS: Both models have general
      quantitative agreement with data from hundreds of genomes, which indicates that
      the domains of a genome are built with a combination of specificity and robust
      self-organizing phenomena. The latter are related to the basic evolutionary
      'moves' of duplication and innovation, and give rise to the observed scaling
      laws, a priori of the specific evolutionary history of a genome. We interpret
      this as the concurrent effect of neutral and selective drives, which increase
      duplication and decrease innovation in larger and more complex genomes. The
      validity of our model would imply that the empirical observation of a small
      number of folds in nature may be a consequence of their evolution.

PMID- 19183450
TI  - Do knowledge infrastructure facilities support evidence-based practice in
      occupational health? An exploratory study across countries among occupational
      physicians enrolled on Evidence-Based Medicine courses.
AB  - BACKGROUND: Evidence-Based Medicine (EBM) is an important method used by
      occupational physicians (OPs) to deliver high quality health care. The presence
      and quality of a knowledge infrastructure is thought to influence the practice of
      EBM in occupational health care. This study explores the facilities in the
      knowledge infrastructure being used by OPs in different countries, and their
      perceived importance for EBM practice. METHODS: Thirty-six OPs from ten
      countries, planning to attend an EBM course and to a large extent recruited via
      the European Association of Schools of Occupational Medicine (EASOM),
      participated in a cross-sectional study. RESULTS: Research and development
      institutes, and knowledge products and tools are used by respectively more than
      72% and more than 80% of the OPs and they are rated as being important for EBM
      practice (more than 65 points (range 0-100)). Conventional knowledge access
      facilities, like traditional libraries, are used often (69%) but are rated as
      less important (46.8 points (range 0-100)) compared to the use of more novel
      facilities, like question-and-answer facilities (25%) that are rated as more
      important (48.9 points (range 0-100)). To solve cases, OPs mostly use non
      evidence-based sources. However, they regard the evidence-based sources that are
      not often used, e.g. the Cochrane library, as important enablers for practising
      EBM. The main barriers are lack of time, payment for full-text articles, language
      barrier (most texts are in English), and lack of skills and support. CONCLUSION:
      This first exploratory study shows that OPs use many knowledge infrastructure
      facilities and rate them as being important for their EBM practice. However, they
      are not used to use evidence-based sources in their practice and face many
      barriers that are comparable to the barriers physicians face in primary health
      care.

PMID- 19183451
TI  - Cost-effectiveness of an integrated 'fast track' rehabilitation service for multi
      trauma patients involving dedicated early rehabilitation intervention programs:
      design of a prospective, multi-centre, non-randomised clinical trial.
AB  - BACKGROUND: In conventional multi-trauma care service (CTCS), patients are
      admitted to hospital via the accident & emergency room. After surgery they are
      transferred to the IC-unit followed by the general surgery ward. Ensuing
      treatment takes place in a hospital's outpatient clinic, a rehabilitation centre,
      a nursing home or the community. Typically, each of the CTCS partners may have
      its own more or less autonomous treatment perspective. Clinical evidence,
      however, suggests that an integrated multi-trauma rehabilitation approach
      ('Supported Fast-track multi-Trauma Rehabilitation Service': SFTRS), featuring:
      1) earlier transfer to a specialised trauma rehabilitation unit; 2) earlier start
      of 'non-weight-bearing' training and multidisciplinary treatment; 3) well
      documented treatment protocols; 4) early individual goal-setting; 5) co
      ordination of treatment between trauma surgeon and physiatrist, and 6) shorter
      lengths-of-stay, may be more (cost-)effective.This paper describes the design of
      a prospective cohort study evaluating the (cost-) effectiveness of SFTRS relative
      to CTCS. METHODS/DESIGN: The study population includes multi-trauma patients,
      admitted to one of the participating hospitals, with an Injury Severity Scale
      score > = 16, complex multiple injuries in several extremities or complex pelvic
      and/or acetabulum fractures. In a prospective cohort study CTCS and SFTRS will be
      contrasted. The inclusion period is 19 months. The duration of follow-up is 12
      months, with measurements taken at baseline, and at 3,6,9 and 12 months post
      injury.Primary outcome measures are 'quality of life' (SF-36) and 'functional
      health status' (Functional Independence Measure). Secondary outcome measures are
      the Hospital Anxiety & Depression Scale, the Mini-Mental State Examination as an
      indicator of cognitive functioning, and the Canadian Occupational Performance
      Measure measuring the extent to which individual ADL treatment goals are met.
      Costs will be assessed using the PROductivity and DISease Questionnaire and a
      cost questionnaire. DISCUSSION: The study will yield results on the efficiency of
      an adapted care service for multi-trauma patients (SFTRS) featuring earlier (and
      condensed) involvement of specialised rehabilitation treatment. Results will show
      whether improved SFTRS logistics, combined with shorter stays in hospital and
      rehabilitation clinic and specialised early rehabilitation training modules are
      more (cost-) effective, relative to CTCS. TRIAL REGISTRATION: Current Controlled
      Trials register (ISRCTN68246661) and Netherlands Trial Register (NTR139).

PMID- 19183452
TI  - Youth tobacco use cessation: 2008 update.
AB  - In this paper, an empirical review of 64 teen tobacco use cessation studies is
      provided. Examined include program contents, delivery modalities, number of
      contacts, and expected quit rates. In addition, means of recruitment and
      retention of smokers in programming are discussed. Also, promising contemporary
      methods of teen smoking cessation are examined, including use of pharmacologic
      adjuncts, electronic technology, and cigarette price increases (and no smoking
      policy). Conclusions are made regarding implications for developing and
      implementing teen tobacco use cessation programs.

PMID- 19183453
TI  - Abnormal glucose regulation in patients with acute ST- elevation myocardial
      infarction-a cohort study on 224 patients.
AB  - BACKGROUND: A high prevalence of impaired glucose tolerance and unknown type 2
      diabetes in patients with coronary heart disease and no previous diagnosis of
      diabetes have been reported. The aims of the present study were to investigate
      the prevalence of abnormal glucose regulation (AGR) 3 months after an acute ST
      elevation myocardial infarction (STEMI) in patients without known glucometabolic
      disturbance, to evaluate the reliability of a 75-g oral glucose tolerance test
      (OGTT) performed very early after an acute STEMI to predict the presence of AGR
      at 3 months, and to study other potential predictors measured in-hospital for AGR
      at 3 months. METHODS: This was an observational cohort study prospectively
      enrolling 224 STEMI patients treated with primary PCI. An OGTT was performed very
      early after an acute STEMI and was repeated in 200 patients after 3 months. We
      summarised the exact agreement observed, and assessed the observed
      reproducibility of the OGTTs performed in-hospital and at follow up. The patients
      were classified into glucometabolic categories defined according to the World
      Health Organisation criteria. AGR was defined as the sum of impaired fasting
      glucose, impaired glucose tolerance and type 2-diabetes. RESULTS: The prevalence
      of AGR at three months was 24.9% (95% CI 19.1, 31.4%), reduced from 46.9% (95% CI
      40.2, 53.6) when measured in-hospital. Only, 108 of 201 (54%) patients remained
      in the same glucometabolic category after a repeated OGTT. High levels of HbA1c
      and admission plasma glucose in-hospital significantly predicted AGR at 3 months
      (p < 0.001, p = 0.040, respectively), and fasting plasma glucose was predictive
      when patients with large myocardial infarction were excluded (p < 0.001).
      CONCLUSION: The prevalence of AGR in STEMI patients was lower than expected.
      HbA1c, admission plasma glucose and fasting plasma glucose measured in-hospital
      seem to be useful as early markers of longstanding glucometabolic disturbance. An
      OGTT performed very early after a STEMI did not provide reliable information on
      long-term glucometabolic state and should probably not be recommended.

PMID- 19183454
TI  - Minimal acupuncture is not a valid placebo control in randomised controlled
      trials of acupuncture: a physiologist's perspective.
AB  - Placebo-control of acupuncture is used to evaluate and distinguish between the
      specific effects and the non-specific ones. During 'true' acupuncture treatment
      in general, the needles are inserted into acupoints and stimulated until deqi is
      evoked. In contrast, during placebo acupuncture, the needles are inserted into
      non-acupoints and/or superficially (so-called minimal acupuncture). A sham
      acupuncture needle with a blunt tip may be used in placebo acupuncture. Both
      minimal acupuncture and the placebo acupuncture with the sham acupuncture needle
      touching the skin would evoke activity in cutaneous afferent nerves. This
      afferent nerve activity has pronounced effects on the functional connectivity in
      the brain resulting in a 'limbic touch response'. Clinical studies showed that
      both acupuncture and minimal acupuncture procedures induced significant
      alleviation of migraine and that both procedures were equally effective. In other
      conditions such as low back pain and knee osteoarthritis, acupuncture was found
      to be more potent than minimal acupuncture and conventional non-acupuncture
      treatment. It is probable that the responses to 'true' acupuncture and minimal
      acupuncture are dependent on the aetiology of the pain. Furthermore, patients and
      healthy individuals may have different responses. In this paper, we argue that
      minimal acupuncture is not valid as an inert placebo-control despite its
      conceptual brilliance.

PMID- 19183455
TI  - Effects of Fructus Piperis Longi extract on fibrotic liver of gamma-irradiated
      rats.
AB  - BACKGROUND: A major biomarker for liver fibrosis is transglutaminase which
      catalyzes cross-linking of epsilon-amines and alpha-glutamyl residues among amino
      acids leading to fibrosis. Fructus Piperis Longi is a common herb used in Chinese
      medicine. The present study evaluates the role of the ethanol extract of Fructus
      Piperis Longi in the modulation of liver function in liver fibrosis. METHODS: Plf
      extract (50 mg/kg) was force-fed to rats every other day 7 days before
      administration of thioacetamide and/or gamma irradiation. Thioacetamid 200 mg/kg
      was intraperitoneally administered to rats twice per week for four weeks. Rats
      were gamma irradiated (2 Gy/week up to a total dose of 8 Gy). Administration of
      Plf ext was extended during thioacetamid and/or irradiation treatment. Animals
      were sacrificed. Biochemical parameters in homogenised liver were tested.
      RESULTS: A significant increase in transglutaminase activity and collagen content
      was recorded in the liver of thioacetamid-treated and/or irradiated rats.
      Significant increases in lipid peroxides, lipid hydroperoxides and conjugated
      dienes associated to significant decreases of reduced glutathione content,
      superoxide dismutase and catalase activities were also recorded. Administration
      of Plf ext treatment reduced the severity of liver fibrosis and oxidative damage
      which was substantiated by amelioration of liver function detected by a decrease
      in serum aspartate aminotransaminase, alanine aminotransferase, alkaline
      phosphatase, gamma glutamyltransferase activities and bilirubin (total, direct
      and indirect) content. CONCLUSION: Treatment of the ethanolic extract of Fructus
      Piperis Longi ameliorated the increase of the activity of tTG enzyme and enhanced
      antioxidant activities in fibrotic liver.

PMID- 19183456
TI  - Large tender abdominal aortic aneurysm presented with concomitant acute
      appendicitis: a case report.
AB  - INTRODUCTION: The management of concurrently occurring abdominal aortic aneurysm
      and another intra-abdominal pathology is controversial and represents a difficult
      management problem for the surgeon. Most surgeons are reluctant to perform a
      second non vascular procedure at the time of the aneurysm repair because of the
      risk of graft infection. Some evidence suggests that the one-stage elective
      surgical treatment in selected patients with concomitant abdominal aortic
      aneurysm and other pathologies; especially Gastro-Intestinal malignancies, is
      safe with superior cost effectiveness. However, there is a major dilemma in the
      management patients with large aneurysm which require an urgent repair and
      presented with concomitant pathologies that carry a high risk of sepsis. In this
      case report, we describe an unusual presentation of a large aneurysm with
      concomitant Acute Appendicitis where both needed an urgent surgical intervention.
      To our best knowledge, there has been no similar case report published in
      literature. CASE REPORT: A 66 years old Caucasian male presented with a dual
      pathology of large abdominal aortic aneurysm and acute appendicitis. The
      diagnosis was confirmed by Computerized Tomography scan of his abdomen. He
      underwent a 2-stage operation; open Appendicectomy followed by open repair of his
      aneurysm to avoid the risk of graft infection. He had an uneventful recovery
      period with a full return to normal life. CONCLUSION: The incidence of patients
      with abdominal aortic aneurysm and coexistent intra-abdominal surgical pathology
      is increasing, and the surgical strategy for those patients remains
      controversial. There are not enough studies that looked directly into the
      management of large abdominal aortic aneurysm which require an urgent repair and
      presented with concomitant pathologies that carry a high risk of sepsis. In such
      situations, simultaneous operations should be avoided because of the risk of
      prosthetic graft infection and priority should be given to the symptomatic or
      most life threatening condition. The second pathology should be dealt with as
      soon as possible; preferably within the same admission. More studies are needed
      to look into this issue; however, this would be rather difficult because of the
      uncommon and complex nature of such presentations.

PMID- 19183458
TI  - A multilevel model for cardiovascular disease prevalence in the US and its
      application to micro area prevalence estimates.
AB  - BACKGROUND: Estimates of disease prevalence for small areas are increasingly
      required for the allocation of health funds according to local need. Both
      individual level and geographic risk factors are likely to be relevant to
      explaining prevalence variations, and in turn relevant to the procedure for small
      area prevalence estimation. Prevalence estimates are of particular importance for
      major chronic illnesses such as cardiovascular disease. METHODS: A multilevel
      prevalence model for cardiovascular outcomes is proposed that incorporates both
      survey information on patient risk factors and the effects of geographic
      location. The model is applied to derive micro area prevalence estimates,
      specifically estimates of cardiovascular disease for Zip Code Tabulation Areas in
      the USA. The model incorporates prevalence differentials by age, sex, ethnicity
      and educational attainment from the 2005 Behavioral Risk Factor Surveillance
      System survey. Influences of geographic context are modelled at both county and
      state level, with the county effects relating to poverty and urbanity. State
      level influences are modelled using a random effects approach that allows both
      for spatial correlation and spatial isolates. RESULTS: To assess the importance
      of geographic variables, three types of model are compared: a model with person
      level variables only; a model with geographic effects that do not interact with
      person attributes; and a full model, allowing for state level random effects that
      differ by ethnicity. There is clear evidence that geographic effects improve
      statistical fit. CONCLUSION: Geographic variations in disease prevalence partly
      reflect the demographic composition of area populations. However, prevalence
      variations may also show distinct geographic 'contextual' effects. The present
      study demonstrates by formal modelling methods that improved explanation is
      obtained by allowing for distinct geographic effects (for counties and states)
      and for interaction between geographic and person variables. Thus an appropriate
      methodology to estimate prevalence at small area level should include geographic
      effects as well as person level demographic variables.

PMID- 19183457
TI  - Heat-shock proteins in infection-mediated inflammation-induced tumorigenesis.
AB  - Inflammation is a necessary albeit insufficient component of tumorigenesis in
      some cancers. Infectious agents directly implicated in tumorigenesis have been
      shown to induce inflammation. This process involves both the innate and adaptive
      components of the immune system which contribute to tumor angiogenesis, tumor
      tolerance and metastatic properties of neoplasms. Recently, heat-shock proteins
      have been identified as mediators of this inflammatory process and thus may
      provide a link between infection-mediated inflammation and subsequent cancer
      development. In this review, the role of heat-shock proteins in infection-induced
      inflammation and carcinogenesis will be discussed.

PMID- 19183459
TI  - Genotypic detection of rifampicin and isoniazid resistant Mycobacterium
      tuberculosis strains by DNA sequencing: a randomized trial.
AB  - BACKGROUND: Tuberculosis is a growing international health concern. It is the
      biggest killer among the infectious diseases in the world today. Early detection
      of drug resistance allows starting of an appropriate treatment. Resistance to
      drugs is due to particular genomic mutations in specific genes of Mycobacterium
      tuberculosis(MTB). The aim of this study was to identify the presence of
      Isoniazid (INH) and Rifampicin(RIF) drug resistance in new and previously treated
      tuberculosis (TB) cases using DNA sequencing. METHODS: This study was carried out
      on 153 tuberculous patients with positive Bactec 460 culture for acid fast
      bacilli. RESULTS: Of the 153 patients, 105 (68.6%) were new cases and 48 (31.4%)
      were previously treated cases. Drug susceptibility testing on Bactec revealed 50
      resistant cases for one or more of the first line antituberculous. Genotypic
      analysis was done only for rifampicin resistant specimens (23 cases) and INH
      resistant specimens (26 cases) to detect mutations responsible for drug
      resistance by PCR amplification of rpoB gene for rifampicin resistant cases and
      KatG gene for isoniazid resistant cases. Finally, DNA sequencing was done for
      detection of mutation within rpoB and KatG genes. Genotypic analysis of RIF
      resistant cases revealed that 20/23 cases (86.9%) of RIF resistance were having
      rpoB gene mutation versus 3 cases (13.1%) having no mutation with a high
      statistical significant difference between them (P < 0.001). Direct sequencing of
      Kat G gene revealed point mutation in 24/26 (92.3%) and the remaining 2/26 (7.7%)
      had wild type KatG i.e. no evidence of mutation with a high statistical
      significant difference between them (P < 0.001). CONCLUSION: We can conclude that
      rifampicin resistance could be used as a useful surrogate marker for estimation
      of multidrug resistance. In addition, Genotypic method was superior to that of
      the traditional phenotypic method which is time-consuming taking several weeks or
      longer.

PMID- 19183460
TI  - Effect of cross exercise on quadriceps acceleration reaction time and subjective
      scores (Lysholm questionnaire) following anterior cruciate ligament
      reconstruction.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) injury or reconstruction can cause
      knee impairments and disability. Knee impairments are related to quadriceps
      performance - accelerated reaction time (ART) - and disability to performance of
      daily living activities which is assessed by questionnaires such as the Lysholm
      knee score. The purposes of this study were to investigate the effect of cross
      exercise, as supplementary rehabilitation to the early phase of ACL
      reconstruction: a) on quadriceps ART at the angles 45 degrees , 60 degrees and 90
      degrees of knee flexion and, b) on the subjective scores of disability in ACL
      reconstructed patients. METHODS: 42 patients who underwent ACL reconstruction
      were randomly divided into 3 groups, two experimental and one control. All groups
      followed the same rehabilitation program. The experimental groups followed 8
      weeks of cross eccentric exercise (CEE) on the uninjured knee; 3 d/w, and 5 d/w
      respectively.Quadriceps ART was measured at 45 degrees , 60 degrees and 90
      degrees of knee flexion pre and nine weeks post-operatively using an isokinetic
      dynamometer. Patients also completed pre and post operatively the Lysholm
      questionnaire whereby subjective scores were recorded. RESULTS: Two factor ANOVA
      showed significant differences in ART at 90 degrees among the groups (F = 4.29, p
      = 0.02, p < 0.05). Post hoc Tukey HSD analysis determined that the significant
      results arose from the first experimental group in comparison to the control (D =
      -0.83, p = 0.01). No significant differences were revealed at 45 degrees and 60
      degrees .Significant differences were also found in the Lysholm score among the
      groups (F = 4.75, p = 0.01, p < 0.05). Post hoc analysis determined that the
      above significant results arose from the first experimental group in comparison
      with the control (D = 7.5, p < 0.01) and from the second experimental in
      comparison with the control (D = 3.78, p = 0.03). CONCLUSION: CEE showed
      improvements on quadriceps ART at 90 degrees at a sequence of 3 d/w and in the
      Lysholm score at a sequence of 3 d/w and 5 d/w respectively on ACL reconstructed
      patients.

PMID- 19183461
TI  - SLC6A3 and body mass index in the Prostate, Lung, Colorectal and Ovarian Cancer
      Screening Trial.
AB  - BACKGROUND: To investigate the contribution of the dopamine transporter to
      dopaminergic reward-related behaviors and anthropometry, we evaluated
      associations between polymorphisms at the dopamine transporter gene(SLC6A3) and
      body mass index (BMI), among participants in the Prostate, Lung, Colorectal and
      Ovarian (PLCO) Cancer Screening Trial. METHODS: Four polymorphisms (rs6350,
      rs6413429, rs6347 and the 3' variable number of tandem repeat (3' VNTR)
      polymorphism) at the SLC6A3 gene were genotyped in 2,364 participants selected
      from the screening arm of PLCO randomly within strata of sex, age and smoking
      history. Height and weight at ages 20 and 50 years and baseline were assessed by
      questionnaire. BMI was calculated and categorized as underweight, normal,
      overweight and obese (<18.5, 18.5-24.9, 25.0-29.9, or > or = 30 kg/m2,
      respectively). Odds ratios (ORs) and 95% confidence intervals (CIs) of SLC6A3
      genotypes and haplotypes were computed using conditional logistic regression.
      RESULTS: Compared with individuals having a normal BMI, obese individuals at the
      time of the baseline study questionnaire were less likely to possess the 3' VNTR
      variant allele with 9 copies of the repeated sequence in a dose-dependent model
      (** is referent; OR*9 = 0.80, OR99 = 0.47, Ptrend = 0.005). Compared with
      individuals having a normal BMI at age 50, overweight individuals (A-C-G-* is
      referent; ORA-C-G-9 = 0.80, 95% CI 0.65-0.99, p = 0.04) and obese individuals (A
      C-G-* is referent; ORA-C-G-9 = 0.70, 95% CI 0.49-0.99, p = 0.04) were less likely
      to possess the haplotype with the 3'variant allele (A-C-G-9). CONCLUSION: Our
      results support a role of genetic variation at the dopamine transporter gene,
      SLC6A3, as a modifier of BMI.

PMID- 19183462
TI  - Nurse-led motivational interviewing to change the lifestyle of patients with type
      2 diabetes (MILD-project): protocol for a cluster, randomized, controlled trial
      on implementing lifestyle recommendations.
AB  - BACKGROUND: The diabetes of many patients is managed in general practice;
      healthcare providers aim to promote healthful behaviors, such as healthful diet,
      adequate physical activity, and smoking cessation. These measures may decrease
      insulin resistance, improve glycemic control, lipid abnormalities, and
      hypertension. They may also prevent cardiovascular disease and complications of
      diabetes. However, professionals do not adhere optimally to guidelines for
      lifestyle counseling. Motivational interviewing to change the lifestyle of
      patients with type 2 diabetes is intended to improve diabetes care in accordance
      with the national guidelines for lifestyle counseling. Primary care nurses will
      be trained in motivational interviewing embedded in structured care in general
      practice. The aim of this paper is to describe the design and methods of a study
      evaluating the effects of the nurses' training on patient outcomes.
      METHODS/DESIGN: A cluster, randomized, controlled trial involving 70 general
      practices (35 practices in the intervention arm and 35 in the control arm)
      starting in March 2007. A total of 700 patients with type 2 diabetes will be
      recruited. The patients in the intervention arm will receive care from the
      primary care nurse, who will receive training in an implementation strategy with
      motivational interviewing as the core component. Other components of this
      strategy will be adaptation of the diabetes protocol to local circumstances,
      introduction of a social map for lifestyle support, and educational and
      supportive tools for sustaining motivational interviewing. The control arm will
      be encouraged to maintain usual care. The effect measures will be the care
      process, metabolic parameters (glycosylated hemoglobin, blood pressure and
      lipids), lifestyle (diet, physical activity, smoking, and alcohol), health
      related quality of life, and patients' willingness to change behaviors. The
      measurements will take place at baseline and after 14 months. DISCUSSION:
      Applying motivational interviewing for patients with diabetes in primary care has
      been studied, but to our knowledge, no other study has yet evaluated the
      implementation and sustainability of motivating and involving patients in day-to
      day diabetes care in general practice. If this intervention proves to be
      effective and cost-effective, large-scale implementation of this nurse-oriented
      intervention will be considered and anticipated. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN68707773.

PMID- 19183464
TI  - Do decision support systems influence variation in prescription?
AB  - BACKGROUND: Translating scientific evidence into daily practice is problematic.
      All kinds of intervention strategies, using educational and/or directive
      strategies, aimed at modifying behavior, have evolved, but have been found only
      partially successful. In this article the focus is on (computerized) decision
      support systems (DSSs). DSSs intervene in physicians' daily routine, as opposed
      to interventions that aim at influencing knowledge in order to change behavior.
      We examined whether general practitioners (GPs) are prescribing in accordance
      with the advice given by the DSS and whether there is less variation in
      prescription when the DSS is used. METHODS: Data were used from the Second Dutch
      National Survey of General Practice (DNSGP2), collected in 2001. A total of 82
      diagnoses, 749811 contacts, 133 physicians, and 85 practices was included in the
      analyses. GPs using the DSS daily were compared to GPs who do not use the DSS.
      Multilevel analyses were used to analyse the data. Two outcome measures were
      chosen: whether prescription was in accordance with the advice of the DSS or not,
      and a measure of concentration, the Herfindahl-Hirschman Index (HHI). RESULTS:
      GPs who use the DSS daily prescribe more according to the advice given in the DSS
      than GPs who do not use the DSS. Contradictory to our expectation there was no
      significant difference between the HHIs for both groups: variation in
      prescription was comparable. CONCLUSION: We studied the use of a DSS for drug
      prescribing in general practice in the Netherlands. The DSS is based on
      guidelines developed by the Dutch College of General Practitioners and
      implemented in the Electronic Medical Systems of the GPs. GPs using the DSS more
      often prescribe in accordance with the advice given in the DSS compared to GPs
      not using the DSS. This finding, however, did not mean that variation is lower;
      variation is the same for GPs using and for GPs not using a DSS. Implications of
      the study are that DSSs can be used to implement guidelines, but that it should
      not be expected that variation is limited.

PMID- 19183463
TI  - A review of the current treatment methods for posthaemorrhagic hydrocephalus of
      infants.
AB  - Posthaemorrhagic hydrocephalus (PHH) is a major problem for premature infants,
      generally requiring lifelong care. It results from small blood clots inducing
      scarring within CSF channels impeding CSF circulation. Transforming growth factor
      - beta is released into CSF and cytokines stimulate deposition of extracellular
      matrix proteins which potentially obstruct CSF pathways. Prolonged raised
      pressures and free radical damage incur poor neurodevelopmental outcomes. The
      most common treatment involves permanent ventricular shunting with all its risks
      and consequences.This is a review of the current evidence for the treatment and
      prevention of PHH and shunt dependency. The Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library) and PubMed (from 1966 to August
      2008) were searched. Trials using random or quasi-random patient allocation for
      any intervention were considered in infants less than 12 months old with PHH.
      Thirteen trials were identified although speculative interventions were also
      evaluated.The literature confirms that lumbar punctures, diuretic drugs and
      intraventricular fibrinolytic therapy can have significant adverse effects and
      fail to prevent shunt dependence, death or disability. There is no evidence that
      postnatal phenobarbital administration prevents intraventricular haemorrhage
      (IVH). Subcutaneous reservoirs and external drains have not been tested in
      randomized controlled trials, but can be useful as a temporising measure.
      Drainage, irrigation and fibrinolytic therapy as a way of removing blood to
      inhibit progressive deposition of matrix proteins, permanent hydrocephalus and
      shunt dependency, are invasive and experimental. Studies of ventriculo-subgaleal
      shunts show potential as a temporary method of CSF diversion, but have high
      infection rates.At present no clinical intervention has been shown to reduce
      shunt surgery in these infants. A ventricular shunt is not advisable in the early
      phase after PHH. Evidence exists that pre-delivery corticosteroid therapy reduces
      mortality and IVH and there may be trends towards reduced disability in the short
      term. There is also evidence that postnatal indomethacin reduces IVH but with no
      effect on mortality or disability. Overall, there is still no definitive
      algorithm for the treatment of PHH or prevention of shunt dependence. New
      therapeutic approaches in neonatal care, including those aimed at pre-empting
      PHH, offer the best hope of improving neurodevelopmental outcomes.

PMID- 19183465
TI  - Evaluation of intracellular signalling pathways in response to insulin-like
      growth factor I in apoptotic-resistant activated human hepatic stellate cells.
AB  - BACKGROUND: Human hepatic stellate cells have been shown to be resistant to
      apoptotic stimuli. This is likely dependent on the activation of anti-apoptotic
      pathways upon transition of these cells to myofibroblast-like cells. In
      particular, previous studies have demonstrated an increased expression of the
      anti-apoptotic protein Bcl-2 and a decreased expression of the pro-apoptotic
      protein Bax during the transition of the hepatic stellate cell phenotype from
      quiescent to myofibroblast-like cells. However, the role and expression of other
      key anti-apoptotic and survival pathways elicited by polypeptide growth factors
      involved in the chronic wound healing process remain to be elucidated. In
      particular, insulin growth factor-I promotes chemotactic and mitogenic effects in
      activated human hepatic stellate cells and these effects are mediated by the
      activation of PI 3-K. The role of insulin growth factor-I as a survival factor in
      human hepatic stellate cells needs to be substantiated. The aim of this study was
      to evaluate the involvement of other key anti-apoptotic pathways such as PI
      3K/Akt/p-Bad in response to insulin growth factor-I. RESULTS: Insulin growth
      factor-I induced activation of Akt followed by Bad phosphorylation after 15
      minutes of incubation. These effects were PI-3k dependent since selective
      inhibitors of this molecule, wortmannin and LY294002, inhibited both Akt and Bad
      phosphorylation. The effect of insulin growth factor-I on the activation of two
      downstream targets of Akt activation, that is, GSK3 and FHKR, both implicated in
      the promotion of cell survival was also investigated. Both targets became
      phosphorylated after 15 minutes of incubation, and these effects were also PI-3K
      dependent. Despite the activation of this survival pathway insulin growth factor
      I did not have a remarkable biological effect, probably because other insulin
      growth factor-I-independent survival pathways were already maximally activated in
      the process of hepatic stellate cell activation. However, after incubation of the
      cells with a strong apoptotic stimuli such as Fas ligand+cycloheximide, a small
      percentage of hepatic stellate cells underwent programmed cell death that was
      partially rescued by insulin growth factor-I. CONCLUSION: In addition to Bcl-2,
      several other anti-apoptotic pathways are responsible for human hepatic stellate
      cell resistance to apoptosis. These features are relevant for the progression and
      limited reversibility of liver fibrosis in humans.

PMID- 19183466
TI  - On the understanding and development of modern physical neurorehabilitation
      methods: robotics and non-invasive brain stimulation.
AB  - The incidence of physical disability in the community resulting from neurological
      dysfunction is predicted to increase in the coming years. The impetus for
      immediate and critical evaluation of physical neurorehabilitation strategies
      stems from the largely incomplete recovery following neurological damage,
      questionable efficacy of individual rehabilitation techniques, and the
      progressive acceptance of evidence-based medicine. The emergent technologies of
      non-invasive brain stimulation (NBS) and rehabilitation robotics enable a better
      understanding of the recovery process, as well as the mechanisms and
      effectiveness of intervention. With a more precise grasp of the relationship
      between dysfunctional and treatment-related plasticity, we can anticipate a move
      toward highly controlled and individualised prescription of rehabilitation. Both
      robotics and NBS can also be used to enhance motor control and learning in
      patients with neurological dysfunction. The merit of these contemporary methods
      as investigative and rehabilitation tools requires clarification and discussion.
      In this thematic series, five cohesive and eloquent papers address this issue
      from leading clinicians and scientists in the fields of robotics, NBS, plasticity
      and motor learning.

PMID- 19183467
TI  - Form and function of damselfish skulls: rapid and repeated evolution into a
      limited number of trophic niches.
AB  - BACKGROUND: Damselfishes (Perciformes, Pomacentridae) are a major component of
      coral reef communities, and the functional diversity of their trophic anatomy is
      an important constituent of the ecological morphology of these systems. Using
      shape analyses, biomechanical modelling, and phylogenetically based comparative
      methods, we examined the anatomy of damselfish feeding among all genera and
      trophic groups. Coordinate based shape analyses of anatomical landmarks were used
      to describe patterns of morphological diversity and determine positions of
      functional groups in a skull morphospace. These landmarks define the lever and
      linkage structures of the damselfish feeding system, and biomechanical analyses
      of this data were performed using the software program JawsModel4 in order to
      calculate the simple mechanical advantage (MA) employed by different skull
      elements during feeding, and to compute kinematic transmission coefficients (KT)
      that describe the efficiency with which angular motion is transferred through the
      complex linkages of damselfish skulls. RESULTS: Our results indicate that
      pomacentrid planktivores are significantly different from other damselfishes,
      that biting MA values and protrusion KT ratios are correlated with pomacentrid
      trophic groups more tightly than KT scores associated with maxillary rotation and
      gape angle, and that the MAs employed by their three biting muscles have evolved
      independently. Most of the biomechanical parameters examined have experienced low
      levels of phylogenetic constraint, which suggests that they have evolved quickly.
      CONCLUSION: Joint morphological and biomechanical analyses of the same anatomical
      data provided two reciprocally illuminating arrays of information. Both analyses
      showed that the evolution of planktivory has involved important changes in
      pomacentrid functional morphology, and that the mechanics of upper jaw kinesis
      have been of great importance to the evolution of damselfish feeding. Our data
      support a tight and biomechanically defined link between structure and the
      functional ecology of fish skulls, and indicate that certain mechanisms for
      transmitting motion through their jaw linkages may require particular anatomical
      configurations, a conclusion that contravenes the concept of "many-to-one
      mapping" for fish jaw mechanics. Damselfish trophic evolution is characterized by
      rapid and repeated shifts between a small number of eco-morphological states, an
      evolutionary pattern that we describe as reticulate adaptive radiation.

PMID- 19183468
TI  - Pleistocene glacial refugia across the Appalachian Mountains and coastal plain in
      the millipede genus Narceus: evidence from population genetic, phylogeographic,
      and paleoclimatic data.
AB  - BACKGROUND: Species that are widespread throughout historically glaciated and
      currently non-glaciated areas provide excellent opportunities to investigate the
      role of Pleistocene climatic change on the distribution of North American
      biodiversity. Many studies indicate that northern animal populations exhibit low
      levels of genetic diversity over geographically widespread areas whereas southern
      populations exhibit relatively high levels. Recently, paleoclimatic data have
      been combined with niche-based distribution modeling to locate possible refugia
      during the Last Glacial Maximum. Using phylogeographic, population, and
      paleoclimatic data, we show that the distribution and mitochondrial data for the
      millipede genus Narceus are consistent with classical examples of Pleistocene
      refugia and subsequent post-glacial population expansion seen in other organismal
      groups. RESULTS: The phylogeographic structure of Narceus reveals a complex
      evolutionary history with signatures of multiple refugia in southeastern North
      America followed by two major northern expansions. Evidence for refugial
      populations were found in the southern Appalachian Mountains and in the coastal
      plain. The northern expansions appear to have radiated from two separate refugia,
      one from the Gulf Coastal Plain area and the other from the mid-Atlantic coastal
      region. Distributional models of Narceus during the Last Glacial Maximum show a
      dramatic reduction from the current distribution, with suitable ecological zones
      concentrated along the Gulf and Atlantic coastal plain. We found a strong
      correlation between these zones of ecological suitability inferred from our paleo
      model with levels of genetic diversity derived from phylogenetic and population
      estimates of genetic structuring. CONCLUSION: The signature of climatic change,
      during and after the Pleistocene, on the distribution of the millipede genus
      Narceus is evident in the genetic data presented. Niche-based historical
      distribution modeling strengthens the conclusions drawn from the genetic data and
      proves useful in identifying probable refugia. Such interdisciplinary
      biogeographic studies provide a comprehensive approach to understanding these
      processes that generate and maintain biodiversity as well as the framework
      necessary to explore questions regarding evolutionary diversification of taxa.

PMID- 19183469
TI  - On gene dosage balance in protein complexes: a comment on Semple JI, Vavouri T,
      Lehner B. A simple principle concerning the robustness of protein complex
      activity to changes in gene expression.

PMID- 19183470
TI  - The Pediatric Obsessive-Compulsive Disorder Treatment Study II: rationale, design
      and methods.
AB  - This paper presents the rationale, design, and methods of the Pediatric Obsessive
      Compulsive Disorder Treatment Study II (POTS II), which investigates two
      different cognitive-behavior therapy (CBT) augmentation approaches in children
      and adolescents who have experienced a partial response to pharmacotherapy with a
      serotonin reuptake inhibitor for OCD. The two CBT approaches test a "single
      doctor" versus "dual doctor" model of service delivery. A specific goal was to
      develop and test an easily disseminated protocol whereby child psychiatrists
      would provide instructions in core CBT procedures recommended for pediatric OCD
      (e.g., hierarchy development, in vivo exposure homework) during routine medical
      management of OCD (I-CBT). The conventional "dual doctor" CBT protocol consists
      of 14 visits over 12 weeks involving: (1) psychoeducation, (2), cognitive
      training, (3) mapping OCD, and (4) exposure with response prevention (EX/RP). I
      CBT is a 7-session version of CBT that does not include imaginal exposure or
      therapist-assisted EX/RP. In this study, we compared 12 weeks of medication
      management (MM) provided by a study psychiatrist (MM only) with two types of CBT
      augmentation: (1) the dual doctor model (MM+CBT); and (2) the single doctor model
      (MM+I-CBT). The design balanced elements of an efficacy study (e.g., random
      assignment, independent ratings) with effectiveness research aims (e.g.,
      differences in specific SRI medications, dosages, treatment providers). The study
      is wrapping up recruitment of 140 youth ages 7-17 with a primary diagnosis of
      OCD. Independent evaluators (IEs) rated participants at weeks 0,4,8, and 12
      during acute treatment and at 3,6, and 12 month follow-up visits. TRIAL
      REGISTRATION: NCT00074815.

PMID- 19183471
TI  - Exclusion of elective nodal irradiation is associated with minimal elective nodal
      failure in non-small cell lung cancer.
AB  - BACKGROUND: Controversy still exists regarding the long-term outcome of patients
      whose uninvolved lymph node stations are not prophylactically irradiated for non
      small cell lung cancer (NSCLC) treated with definitive radiotherapy. To determine
      the frequency of elective nodal failure (ENF) and in-field failure (IFF), we
      examined a large cohort of patients with NSCLC staged with positron emission
      tomography (PET)/computed tomography (CT) and treated with 3-dimensional
      conformal radiotherapy (3D-CRT) that excluded uninvolved lymph node stations.
      METHODS: We retrospectively reviewed the records of 115 patients with non-small
      cell lung cancer treated at our institution with definitive radiation therapy
      with or without concurrent chemotherapy (CHT). All patients were treated with 3D
      CRT, including nodal regions determined by CT or PET to be disease involved.
      Concurrent platinum-based CHT was administered for locally advanced disease.
      Patients were analyzed in follow-up for survival, local regional recurrence, and
      distant metastases (DM). RESULTS: The median follow-up time was 18 months (3 to
      44 months) among all patients and 27 months (6 to 44 months) among survivors. The
      median overall survival, 2-year actuarial overall survival and disease-free
      survival were 19 months, 38%, and 28%, respectively. The majority of patients
      died from DM, the overall rate of which was 36%. Of the 31 patients with local
      regional failure, 26 (22.6%) had IFF, 5 (4.3%) had ENF and 2 (1.7%) had isolated
      ENF. For 88 patients with stage IIIA/B, the frequencies of IFF, any ENF, isolated
      ENF, and DM were 23 (26%), 3 (9%), 1 (1.1%) and 36 (40.9%), respectively. The
      comparable rates for the 22 patients with early stage node-negative disease
      (stage IA/IB) were 3 (13.6%), 1(4.5%), 0 (0%), and 5 (22.7%), respectively.
      CONCLUSION: We observed only a 4.3% recurrence of any ENF and a 1.7% recurrence
      of isolated ENF in patients with NSCLC treated with definitive 3D-CRT without
      prophylactic irradiation of uninvolved lymph node stations. Thus, distant
      metastasis and IFF remain the primary causes of treatment failure and cancer
      death in such patients, suggesting little value of ENI in this cohort.

PMID- 19183472
TI  - Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis.
AB  - BACKGROUND: Lipid-rich tumours have been associated with increased cancer
      metastasis and aggressive clinical behaviours. Nonetheless, pathologists cannot
      classify lipid-rich tumours as a clinically distinctive form of carcinoma due to
      a lack of mechanistic understanding on the roles of lipids in cancer development.
      METHODS: Coherent anti-Stokes Raman scattering (CARS) microscopy is employed to
      study cancer cell behaviours in excess lipid environments in vivo and in vitro.
      The impacts of a high fat diet on cancer development are evaluated in a Balb/c
      mice cancer model. Intravital flow cytometry and histology are employed to
      enumerate cancer cell escape to the bloodstream and metastasis to lung tissues,
      respectively. Cancer cell motility and tissue invasion capability are also
      evaluated in excess lipid environments. RESULTS: CARS imaging reveals
      intracellular lipid accumulation is induced by excess free fatty acids (FFAs).
      Excess FFAs incorporation onto cancer cell membrane induces membrane phase
      separation, reduces cell-cell contact, increases surface adhesion, and promotes
      tissue invasion. Increased plasma FFAs level and visceral adiposity are
      associated with early rise in circulating tumour cells and increased lung
      metastasis. Furthermore, CARS imaging reveals FFAs-induced lipid accumulation in
      primary, circulating, and metastasized cancer cells. CONCLUSION: Lipid-rich
      tumours are linked to cancer metastasis through FFAs-induced physical
      perturbations on cancer cell membrane. Most importantly, the revelation of lipid
      rich circulating tumour cells suggests possible development of CARS intravital
      flow cytometry for label-free detection of early-stage cancer metastasis.

PMID- 19183473
TI  - Preliminary reference values for electrocardiography, echocardiography and
      myocardial morphometry in the European brown hare (Lepus europaeus).
AB  - The study aimed at defining reference values for electrocardiographic (ECG) and
      echocardiographic parameters as well as macroscopic dimensions of the heart and
      microscopic dimensions of cardiomyocytes in the European brown hare. The studies
      were conducted on 30 adult, clinically healthy hares of either sex caught in
      Poland. ECG and echocardiography were performed supravitally on anaesthetized
      hares. After euthanasia, gross and microscopic myocardial and cardiomyocyte
      dimensions were determined. Heart rate amounted to 140 +/- 37.5 beats/min, the
      leading rhythm involved the sinus rhythm. P wave time was 26 +/- 5 ms, PQ time
      was 80 ms, QRS time was 29 +/- 3.5 ms, and ST was 97.5 +/- 7 ms. Echocardiography
      determined a left ventricular wall end-diastolic diameter of 8.6 +/- 2.0 mm and
      an intraventricular septum end-diastolic diameter of 5.75 +/- 1.0 mm. The
      thickness of the interventricular septum corresponded to that of the free wall of
      the left ventricle, a finding consistent with physiological hypertrophy.
      Preliminary reference values were established for echocardiography. The findings
      were similar to those obtained at necropsy. The ECG and echocardiographic studies
      represent the first supravital examination of cardiac function in the hare. The
      obtained results illustrate adaptation of hare's myocardium to its mode of life.
      The cardiac findings resemble the athlete's heart syndrome described in humans.
      The findings may prove useful in further studies on the physiology of the cardio
      vascular system in the hare.

PMID- 19183474
TI  - Sequence mining and transcript profiling to explore cyst nematode parasitism.
AB  - BACKGROUND: Cyst nematodes are devastating plant parasites that become sedentary
      within plant roots and induce the transformation of normal plant cells into
      elaborate feeding cells with the help of secreted effectors, the parasitism
      proteins. These proteins are the translation products of parasitism genes and are
      secreted molecular tools that allow cyst nematodes to infect plants. RESULTS: We
      present here the expression patterns of all previously described parasitism genes
      of the soybean cyst nematode, Heterodera glycines, in all major life stages
      except the adult male. These insights were gained by analyzing our gene
      expression dataset from experiments using the Affymetrix Soybean Genome Array
      GeneChip, which contains probeset sequences for 6,860 genes derived from
      preparasitic and parasitic H. glycines life stages. Targeting the identification
      of additional H. glycines parasitism-associated genes, we isolated 633 genes
      encoding secretory proteins using algorithms to predict secretory signal
      peptides. Furthermore, because some of the known H. glycines parasitism proteins
      have strongest similarity to proteins of plants and microbes, we searched for
      predicted protein sequences that showed their highest similarities to plant or
      microbial proteins and identified 156 H. glycines genes, some of which also
      contained a signal peptide. Analyses of the expression profiles of these genes
      allowed the formulation of hypotheses about potential roles in parasitism. This
      is the first study combining sequence analyses of a substantial EST dataset with
      microarray expression data of all major life stages (except adult males) for the
      identification and characterization of putative parasitism-associated proteins in
      any parasitic nematode. CONCLUSION: We have established an expression atlas for
      all known H. glycines parasitism genes. Furthermore, in an effort to identify
      additional H. glycines genes with putative functions in parasitism, we have
      reduced the currently known 6,860 H. glycines genes to a pool of 788 most
      promising candidate genes (including known parasitism genes) and documented their
      expression profiles. Using our approach to pre-select genes likely involved in
      parasitism now allows detailed functional analyses in a manner not feasible for
      larger numbers of genes. The generation of the candidate pool described here is
      an important enabling advance because it will significantly facilitate the
      unraveling of fascinating plant-animal interactions and deliver knowledge that
      can be transferred to other pathogen-host systems. Ultimately, the exploration of
      true parasitism genes verified from the gene pool delineated here will identify
      weaknesses in the nematode life cycle that can be exploited by novel anti
      nematode efforts.

PMID- 19183475
TI  - Pumpless extracorporeal interventional lung assist in patients with acute
      respiratory distress syndrome: a prospective pilot study.
AB  - INTRODUCTION: Pumpless interventional lung assist (iLA) is used in patients with
      acute respiratory distress syndrome (ARDS) aimed at improving extracorporeal gas
      exchange with a membrane integrated in a passive arteriovenous shunt. In previous
      studies, feasibility and safety of the iLA system was demonstrated, but no
      survival benefit was observed. In the present pilot study we tested the
      hypothesis that timely initiation of iLA using clear algorithms and an improved
      cannulation technique will positively influence complication rates and management
      of lung protective ventilation. METHODS: iLA was implemented in 51 patients from
      multiple aetiologies meeting ARDS-criteria (American-European Consensus) for more
      than 12 hours. Initiation of iLA followed an algorithm for screening, careful
      evaluation and insertion technique. Patients with cardiac insufficiency or severe
      peripheral vascular disease were not considered suitable for iLA. Arterial and
      venous cannulae were inserted using a new strategy (ultrasound evaluation of
      vessels by an experienced team, using cannulae of reduced diameter). The
      incidence of complications and the effects on tidal volumes and inspiratory
      plateau pressures were primary outcome parameters, while oxygenation improvement
      and carbon dioxide removal capabilities were secondary study parameters. RESULTS:
      Initiation of iLA resulted in a marked removal in arterial carbon dioxide
      allowing a rapid reduction in tidal volume (<or= 6 ml/kg) and inspiratory plateau
      pressure. Adverse events occurred in 6 patients (11.9%). The hospital mortality
      rate was 49%. CONCLUSIONS: The use of an indication algorithm for iLA in early
      ARDS, combined with a refined application technique was associated with efficient
      carbon dioxide removal and a reduced incidence of adverse events. iLA could serve
      as an extracorporeal assist to support mechanical ventilation by enabling low
      tidal volume and a reduced inspiratory plateau pressure.

PMID- 19183476
TI  - A four year longitudinal sero-epidemiological study of bovine herpesvirus type-1
      (BHV-1) in adult cattle in 107 unvaccinated herds in south west England.
AB  - BACKGROUND: Bovine herpesvirus type-1 (BHV-1) is an important pathogen of cattle
      that presents with a variety of clinical signs, including the upper respiratory
      tract infection infectious bovine rhinotracheitis (IBR). A seroepidemiological
      study of BHV-1 antibodies was conducted in England from 2002 - 2004: 29,782 blood
      samples were taken from 15,736 cattle from 114 herds which were visited on up to
      three occasions. Antibody concentration was measured using a commercial ELISA.
      Farm management information was collected using an interview questionnaire, and
      herd size and cattle movements were obtained from the cattle tuberculosis testing
      database and the British Cattle Movement Service. Hierarchical statistical models
      were used to investigate associations between cattle and herd variables and the
      continuous outcome percentage positive (PP) values from the ELISA test in
      unvaccinated herds. RESULTS: There were 7 vaccinated herds, all with at least one
      seropositive bovine. In unvaccinated herds 83.2% had at least one BHV-1
      seropositive bovine, and the mean cattle and herd BHV-1 seroprevalence were 42.5%
      and 43.1% respectively. There were positive associations between PP value, age,
      herd size, presence of dairy cattle. Adult cattle in herds with grower cattle had
      lower PP values than those in herds without grower cattle. Purchased cattle had
      significantly lower PP values than homebred cattle, whereas cattle in herds that
      were totally restocked after the foot-and-mouth epidemic in 2001 had
      significantly higher PP values than those in continuously stocked herds. Samples
      taken in spring and summer had significantly lower PP values than those taken in
      winter, whereas those taken in autumn had significantly higher PP values than
      those taken in winter. The risks estimated from a logistic regression model with
      a binary outcome (seropositive yes/no) were similar. CONCLUSION: The prevalence
      of BHV-1 seropositivity in cattle and herds has increased since the 1970s.
      Although the study population prevalence of BHV-1 was temporally stable during
      study period, the associations between serological status and cattle age, herd
      size, herd type, presence of young stock and restocked versus continuously
      stocked herds indicate that there is heterogeneity between herds and so potential
      for further spread of BHV-1 within and between herds.

PMID- 19183477
TI  - Sequence Searcher: A Java tool to perform regular expression and fuzzy searches
      of multiple DNA and protein sequences.
AB  - BACKGROUND: Many sequence-searching tools have limiting factors for their use.
      For example, they may be platform specific, enforce restrictive size limits and
      sequences to be searched, or only allow searches of one of DNA or protein.
      FINDINGS: We present an easy-to-use, fast, platform-independent tool to search
      for amino acid or nucleotide patterns within one or many protein or nucleic acid
      sequences. The user can choose to search for regular expressions or perform a
      fuzzy search in which a particular number of errors is accepted during matching
      of a sequence. Positions of mismatches in fuzzy searches are displayed
      graphically the user. CONCLUSION: SeqS provides an improved feature set and
      functions as a stand-alone tool or could be integrated into other bioinformatics
      platforms.

PMID- 19183478
TI  - Ab initio and template-based prediction of multi-class distance maps by two
      dimensional recursive neural networks.
AB  - BACKGROUND: Prediction of protein structures from their sequences is still one of
      the open grand challenges of computational biology. Some approaches to protein
      structure prediction, especially ab initio ones, rely to some extent on the
      prediction of residue contact maps. Residue contact map predictions have been
      assessed at the CASP competition for several years now. Although it has been
      shown that exact contact maps generally yield correct three-dimensional
      structures, this is true only at a relatively low resolution (3-4 A from the
      native structure). Another known weakness of contact maps is that they are
      generally predicted ab initio, that is not exploiting information about potential
      homologues of known structure. RESULTS: We introduce a new class of distance
      restraints for protein structures: multi-class distance maps. We show that C
      alpha trace reconstructions based on 4-class native maps are significantly better
      than those from residue contact maps. We then build two predictors of 4-class
      maps based on recursive neural networks: one ab initio, or relying on the
      sequence and on evolutionary information; one template-based, or in which
      homology information to known structures is provided as a further input. We show
      that virtually any level of sequence similarity to structural templates (down to
      less than 10%) yields more accurate 4-class maps than the ab initio predictor. We
      show that template-based predictions by recursive neural networks are
      consistently better than the best template and than a number of combinations of
      the best available templates. We also extract binary residue contact maps at an 8
      A threshold (as per CASP assessment) from the 4-class predictors and show that
      the template-based version is also more accurate than the best template and
      consistently better than the ab initio one, down to very low levels of sequence
      identity to structural templates. Furthermore, we test both ab-initio and
      template-based 8 A predictions on the CASP7 targets using a pre-CASP7 PDB, and
      find that both predictors are state-of-the-art, with the template-based one far
      outperforming the best CASP7 systems if templates with sequence identity to the
      query of 10% or better are available. Although this is not the main focus of this
      paper we also report on reconstructions of C alpha traces based on both ab initio
      and template-based 4-class map predictions, showing that the latter are generally
      more accurate even when homology is dubious. CONCLUSION: Accurate predictions of
      multi-class maps may provide valuable constraints for improved ab initio and
      template-based prediction of protein structures, naturally incorporate multiple
      templates, and yield state-of-the-art binary maps. Predictions of protein
      structures and 8 A contact maps based on the multi-class distance map predictors
      described in this paper are freely available to academic users at the url
      http://distill.ucd.ie/.

PMID- 19183479
TI  - The influence of context and process when implementing e-health.
AB  - BACKGROUND: Investing in computer-based information systems is notoriously risky,
      since many systems fail to become routinely used as part of everyday working
      practices, yet there is clear evidence about the management practices which
      improve the acceptance and integration of such systems. Our aim in this study was
      to identify to what extent these generic management practices are evident in e
      health projects, and to use that knowledge to develop a theoretical model of e
      health implementation. This will support the implementation of appropriate e
      health systems. METHODS: This study consisted of qualitative semi-structured
      interviews with managers and health professionals in Scotland, UK. We contacted
      the Scottish Ethics Committee, who advised that formal application to that body
      was not necessary for this study. The interview guide aimed to identify the
      issues which respondents believed had affected the successful implementation of e
      health projects. We drew on our research into information systems in other
      sectors to identify likely themes and questions, which we piloted and revised.
      Eighteen respondents with experience of e-health projects agreed to be
      interviewed. These were recorded, transcribed, coded, and then analysed with
      'Nvivo' data analysis software. RESULTS: Respondents identified factors in the
      context of e-health projects which had affected implementation, including clarity
      of the strategy; supportive structures and cultures; effects on working
      processes; and how staff perceived the change. The results also identified useful
      implementation practices such as balancing planning with adaptability; managing
      participation; and using power effectively. CONCLUSION: The interviews confirmed
      that the contextual factors that affect implementation of information systems in
      general also affect implementation of e-health projects. As expected, these take
      place in an evolving context of strategies, structures, cultures, working
      processes and people. Respondents also confirmed that those managing such
      projects seek to change these contexts through observable implementation
      processes of planning, adaptation, participation and using power. This study
      confirms that research to support the delivery of appropriate e-health projects
      can usefully draw on the experience of information systems in other sectors.

PMID- 19183480
TI  - Postnatal quality of life in women after normal vaginal delivery and caesarean
      section.
AB  - BACKGROUND: Caesarean section might increase the incidence of surgical
      interventions and problems resulting from hospitalization and thus affecting
      quality of life in women after delivery. This study aimed to compare quality of
      life in women after normal delivery and caesarean section. METHODS: This was a
      prospective study. A sample of women with normal delivery and caesarean section
      from 5 health care centers in Isfahan, Iran were entered into the study. Quality
      of life was measured using the SF-36 at two points in time (time 1: 6 to 8 weeks
      after delivery; time 2: 12 to 14 weeks after delivery). Data were analyzed to
      compare quality of life in the two study groups. RESULTS: In all 100 women were
      interviewed (50 with normal delivery and 50 with caesarean section). Postnatal
      quality of life in both groups was improved from time 1 to time 2. However,
      comparing the mean scores between the normal and caesarean delivery groups the
      results showed that in general the normal vaginal delivery group had a better
      quality of life for almost all subscales in both assessment times. The
      differences were significant for vitality (mean score 62.9 vs. 54.4 P = 0.03) and
      mental health (mean score 75.1 vs. 66.7, P = 0.03) at first assessment and for
      physical functioning (mean score 88.4 vs. 81.5, P = 0.03) at second evaluation.
      However, comparing the findings within each group the analysis showed that the
      normal vaginal delivery group improved more on physical health related quality of
      life while the caesarean section group improved more on mental health related
      quality of life. CONCLUSION: Although the study did not show a clear cut benefit
      in favor of either methods of delivery that are normal vaginal delivery or
      caesarean section, the findings suggest that normal vaginal delivery might lead
      to a better quality of life especially resulting in a superior physical health.
      Indeed in the absence of medical indications normal vaginal delivery might be
      better to be considered as the first priority in term pregnancy.

PMID- 19183481
TI  - Metabolite profiling studies in Saccharomyces cerevisiae: an assisting tool to
      prioritize host targets for antiviral drug screening.
AB  - BACKGROUND: The cellular proteins Pat1p, Lsm1p, and Dhh1p are required for the
      replication of some positive-strand viruses and therefore are potential targets
      for new antiviral drugs. To prioritize host targets for antiviral drug screening
      a comparative metabolome analysis in Saccharomyces cerevisiae reference strain
      BY4742 Matalpha his3Delta1 leu2Delta0 lys2Delta0 ura3Delta0 and deletion strains
      pat1Delta, lsm1Delta and dhh1Delta was performed. RESULTS: GC/MS analysis
      permitted the quantification of 47 polar metabolites and the identification of 41
      of them. Metabolites with significant variation between the strains were
      identified using partial least squares to latent structures discriminate analysis
      (PLS-DA). The analysis revealed least differences of pat1Delta to the reference
      strain as characterized by Euclidian distance of normalized peak areas. The
      growth rate and specific production rates of ethanol and glycerol were also most
      similar with this strain. CONCLUSION: From these results we hypothesize that the
      human analog of yeast Pat1p is most likely the best drug target candidate.

PMID- 19183482
TI  - Psychometric characteristics of the ankylosing spondylitis quality of life
      questionnaire, short form 36 health survey, and functional assessment of chronic
      illness therapy-fatigue subscale.

PMID- 19183483
TI  - Screening and association testing of common coding variation in steroid hormone
      receptor co-activator and co-repressor genes in relation to breast cancer risk:
      the Multiethnic Cohort.
AB  - BACKGROUND: Only a limited number of studies have performed comprehensive
      investigations of coding variation in relation to breast cancer risk. Given the
      established role of estrogens in breast cancer, we hypothesized that coding
      variation in steroid receptor coactivator and corepressor genes may alter inter
      individual response to estrogen and serve as markers of breast cancer risk.
      METHODS: We sequenced the coding exons of 17 genes (EP300, CCND1, NME1, NCOA1,
      NCOA2, NCOA3, SMARCA4, SMARCA2, CARM1, FOXA1, MPG, NCOR1, NCOR2, CALCOCO1, PRMT1,
      PPARBP and CREBBP) suggested to influence transcriptional activation by steroid
      hormone receptors in a multiethnic panel of women with advanced breast cancer (n
      = 95): African Americans, Latinos, Japanese, Native Hawaiians and European
      Americans. Association testing of validated coding variants was conducted in a
      breast cancer case-control study (1,612 invasive cases and 1,961 controls) nested
      in the Multiethnic Cohort. We used logistic regression to estimate odds ratios
      for allelic effects in ethnic-pooled analyses as well as in subgroups defined by
      disease stage and steroid hormone receptor status. We also investigated effect
      modification by established breast cancer risk factors that are associated with
      steroid hormone exposure. RESULTS: We identified 45 coding variants with
      frequencies > or = 1% in any one ethnic group (43 non-synonymous variants). We
      observed nominally significant positive associations with two coding variants in
      ethnic-pooled analyses (NCOR2: His52Arg, OR = 1.79; 95% CI, 1.05-3.05; CALCOCO1:
      Arg12His, OR = 2.29; 95% CI, 1.00-5.26). A small number of variants were
      associated with risk in disease subgroup analyses and we observed no strong
      evidence of effect modification by breast cancer risk factors. Based on the large
      number of statistical tests conducted in this study, the nominally significant
      associations that we observed may be due to chance, and will need to be confirmed
      in other studies. CONCLUSION: Our findings suggest that common coding variation
      in these candidate genes do not make a substantial contribution to breast cancer
      risk in the general population. Cataloging and testing of coding variants in
      coactivator and corepressor genes should continue and may serve as a valuable
      resource for investigations of other hormone-related phenotypes, such as inter
      individual response to hormonal therapies used for cancer treatment and
      prevention.

PMID- 19183484
TI  - Over half of breakpoints in gene pairs involved in cancer-specific recurrent
      translocations are mapped to human chromosomal fragile sites.
AB  - BACKGROUND: Gene rearrangements such as chromosomal translocations have been
      shown to contribute to cancer development. Human chromosomal fragile sites are
      regions of the genome especially prone to breakage, and have been implicated in
      various chromosome abnormalities found in cancer. However, there has been no
      comprehensive and quantitative examination of the location of fragile sites in
      relation to all chromosomal aberrations. RESULTS: Using up-to-date databases
      containing all cancer-specific recurrent translocations, we have examined 444
      unique pairs of genes involved in these translocations to determine the
      correlation of translocation breakpoints and fragile sites in the gene pairs. We
      found that over half (52%) of translocation breakpoints in at least one gene of
      these gene pairs are mapped to fragile sites. Among these, we examined the DNA
      sequences within and flanking three randomly selected pairs of translocation
      prone genes, and found that they exhibit characteristic features of fragile DNA,
      with frequent AT-rich flexibility islands and the potential of forming highly
      stable secondary structures. CONCLUSION: Our study is the first to examine gene
      pairs involved in all recurrent chromosomal translocations observed in tumor
      cells, and to correlate the location of more than half of breakpoints to
      positions of known fragile sites. These results provide strong evidence to
      support a causative role for fragile sites in the generation of cancer-specific
      chromosomal rearrangements.

PMID- 19183485
TI  - Tracking costs of virulence in natural populations of the wheat pathogen,
      Puccinia striiformis f.sp.tritici.
AB  - BACKGROUND: Costs of adaptation play an important role in host-parasite
      coevolution. For parasites, evolving the ability to circumvent host resistance
      may trade off with subsequent growth or transmission. Such costs of virulence
      (sensu plant pathology) limit the spread of all-infectious genotypes and thus
      facilitate the maintenance of genetic polymorphism in both host and parasite. We
      investigated costs of three virulence factors in Puccinia striiformis
      f.sp.tritici, a fungal pathogen of wheat (Triticum aestivum). RESULTS: In
      pairwise competition experiments, we compared the fitness of near-isogenic
      genotypes that differed by a single virulence factor. Two virulence factors
      (vir4, vir6) imposed substantial fitness costs in the absence of the
      corresponding resistance genes. In contrast, the vir9 virulence factor conferred
      a strong competitive advantage to several isolates, and this for different host
      cultivars and growing seasons. In part, the experimentally derived fitness costs
      and benefits are consistent with frequency changes of these virulence factors in
      the French pathogen population. CONCLUSION: Our results illustrate the variation
      in the evolutionary trajectories of virulence mutations and the potential role of
      compensatory mutations. Anticipation of such variable evolutionary outcomes
      represents a major challenge for plant breeding strategies. More generally, we
      believe that agro-patho-systems can provide valuable insight in (co)evolutionary
      processes in host-parasite systems.

PMID- 19183486
TI  - Surface proteins that promote adherence of Staphylococcus aureus to human
      desquamated nasal epithelial cells.
AB  - BACKGROUND: The natural habitat of Staphylococcus aureus is the moist squamous
      epithelium in the anterior nares. About 20% of the human population carry S.
      aureus permanently in their noses and another 60% of individuals are intermittent
      carriers. The ability of S. aureus to colonize the nasal epithelium is in part
      due to expression of surface proteins clumping factor B (ClfB) and the iron
      regulated surface determinant A (IsdA), which promote adhesion to desquamated
      epithelial cells present in the anterior part of the nasal vestibule. S. aureus
      strain Newman defective in IsdA and ClfB exhibited reduced but not completely
      defective adherence to squamous cells in indicating that other cell surface
      components might also contribute. RESULTS: Surface proteins IsdA, ClfB, and the
      serine-aspartic acid repeat proteins SdrC, SdrD and SdrE were investigated to
      determine their contribution to the adherence of S. aureus to desquamated nasal
      epithelial cells. This was achieved by expression of ClfB, IsdA, SdrC, SdrD and
      SdrE on the surface of the surrogate Gram-positive host Lactococcus lactis and by
      isolating mutants of S. aureus Newman defective in one or more factor. The level
      of adherence of strains to squamous cells isolated from the nares of volunteers
      was measured. Results consistently showed that ClfB, IsdA, SdrC and SdrD each
      contributed to the ability of S. aureus to adhere to squamous cells. A mutant
      lacking all four proteins was completely defective in adherence. CONCLUSION: The
      ability of S. aureus Newman to adhere to desquamated nasal epithelial cells is
      multifactorial and involves SdrD and SdrC as well as ClfB and IsdA.

PMID- 19183487
TI  - A method for statistically comparing spatial distribution maps.
AB  - BACKGROUND: Ecological niche modeling is a method for estimation of species
      distributions based on certain ecological parameters. Thus far, empirical
      determination of significant differences between independently generated
      distribution maps for a single species (maps which are created through equivalent
      processes, but with different ecological input parameters), has been challenging.
      RESULTS: We describe a method for comparing model outcomes, which allows a
      statistical evaluation of whether the strength of prediction and breadth of
      predicted areas is measurably different between projected distributions. To
      create ecological niche models for statistical comparison, we utilized GARP
      (Genetic Algorithm for Rule-Set Production) software to generate ecological niche
      models of human monkeypox in Africa. We created several models, keeping constant
      the case location input records for each model but varying the ecological input
      data. In order to assess the relative importance of each ecological parameter
      included in the development of the individual predicted distributions, we
      performed pixel-to-pixel comparisons between model outcomes and calculated the
      mean difference in pixel scores. We used a two sample Student's t-test, (assuming
      as null hypothesis that both maps were identical to each other regardless of
      which input parameters were used) to examine whether the mean difference in
      corresponding pixel scores from one map to another was greater than would be
      expected by chance alone. We also utilized weighted kappa statistics, frequency
      distributions, and percent difference to look at the disparities in pixel scores.
      Multiple independent statistical tests indicated precipitation as the single most
      important independent ecological parameter in the niche model for human monkeypox
      disease. CONCLUSION: In addition to improving our understanding of the natural
      factors influencing the distribution of human monkeypox disease, such pixel-to
      pixel comparison tests afford users the ability to empirically distinguish the
      significance of each of the diverse environmental parameters included in the
      modeling process. This method will be particularly useful in situations where the
      outcomes (maps) appear similar upon visual inspection (as are generated with
      other modeling programs such as MAXENT), as it allows an investigator the
      capacity to explore subtle differences among ecological parameters and to
      demonstrate the individual importance of these factors within an overall model.

PMID- 19183488
TI  - A survey of pediatricians' attitudes regarding influenza immunization in
      children.
AB  - BACKGROUND: The Advisory Committee on Immunization Practices advocates that
      influenza immunization is the most effective method for prevention of illness due
      to influenza. Recommendations for vaccination of children against influenza have
      been revised several times since 2002, and as of 2008 include all children 6
      months to 18 years of age. Nevertheless, influenza immunization rates have
      remained low. METHODS: We surveyed practicing pediatricians in Maryland in the
      spring of 2007 to determine their attitudes and practices toward childhood
      influenza immunization. RESULTS: The overall response to the survey was 21%. A
      total of 61% of respondents reported that immunization either is cost neutral or
      produces a loss, and 36.6% noted it was minimally profitable. Eighty-six percent
      of respondents were receptive to supporting school-based immunization programs,
      and 61% indicated that they would participate in such programs. Respondents
      reported higher rates of immunization of select patient groups than those noted
      by the Centers for Disease Control and Prevention CONCLUSION: Vaccination was
      reported to occur at multiple types of patient encounters, as recommended. Survey
      respondents stated that practice-based immunization was not a profitable service.
      Pediatricians were supportive of school-based immunization programs, and more
      than half stated they would be actively involved in such programs. School-based
      programs may be critical to achieving high vaccination coverage in the school
      aged population.

PMID- 19183489
TI  - Percutaneous retrieval of a biliary stent after migration and ileal perforation.
AB  - We present a case of a migrated biliary stent that resulted in a distal small
      bowel perforation, abscess formation and high grade partial small bowel
      obstruction in a medically stable patient without signs of sepsis or diffuse
      peritonitis. We performed a percutaneous drainage of the abscess followed by
      percutaneous retrieval of the stent. The entero-peritoneal fistula closed
      spontaneously with a drain in place. We conclude, migrated biliary stents
      associated with perforation distal to the Ligament of Trietz (LOT), may be
      treated by percutaneous drainage of the abscess and retrieval of the stent from
      the peritoneal cavity, even when associated with a large intra-abdominal abscess.

PMID- 19183491
TI  - Hypercalcemia-leukocytosis syndrome in a patient with cavitating squamous cell
      carcinoma of the lung.
AB  - INTRODUCTION: Lung cancer is the leading cause of death among the cancers seen in
      the United States. Hypercalcemia and leukocytosis are two common paraneoplastic
      syndromes associated with lung cancer. Unfortunately patients presenting with
      Hypercalcemia- leukocytosis syndrome has a worse prognosis than patients
      presenting with lung cancer alone. CASE PRESENTATION: We present a 67 yr old
      Caucasian male with a history of active smoking presenting as pneumonia being
      diagnosed as cavitating squamous cell carcinoma of the lung with hypercalcemia
      leukocytosis syndrome CONCLUSION: There should be a high degree of suspicion to
      diagnose lung cancer in patients presenting with symptoms of paraneoplastic
      syndrome.

PMID- 19183490
TI  - Influence of brain-derived neurotrophic factor on pathfinding of dentate granule
      cell axons, the hippocampal mossy fibers.
AB  - Mossy fibers, the dentate granule cell axons, are generated throughout an
      animal's lifetime. Mossy fiber paths and synapses are primarily restricted to the
      stratum lucidum within the CA3 region. Brain-derived neurotrophic factor (BDNF),
      a neurotrophin family protein that activates Trk neurotrophin receptors, is
      highly expressed in the stratum lucidum in an activity-dependent manner. The
      addition of a Trk neurotrophin receptor inhibitor, K252a, to cultured hippocampal
      slices induced aberrant extension of mossy fibers into ectopic regions. BDNF
      overexpression in granule cells ameliorated the mossy fiber pathway abnormalities
      caused by a submaximal dose of K252a. A similar rescue was observed when BDNF was
      expressed in CA3 pyramidal cells, most notably in mossy fibers distal to the
      expression site. These findings are the first to clarify the role of BDNF in
      mossy fiber pathfinding, not as an attractant cue but as a regulator, possibly
      acting in a paracrine manner. This effect of BDNF may be as a signal for new
      fibers to fasciculate and extend further to form synapses with neurons that are
      far from active BDNF-expressing synapses. This mechanism would ensure the
      emergence of new independent dentate gyrus-CA3 circuits by the axons of new-born
      granule cells.

PMID- 19183492
TI  - Inhibition of B16 melanoma growth and metastasis in C57BL mice by vaccination
      with a syngeneic endothelial cell line.
AB  - BACKGROUND: Key role of angiogenesis in tumor growth and metastasis based on
      accumulating evidence and recent progress of immunotherapy have led us to
      investigate vaccine therapy targeting tumor angiogenesis. METHODS: C57BL/6J mice
      were vaccinated with a syngeneic endothelial cell line Tpit/E by subcutaneous
      injection once a week. Prior to ninth vaccination, the mice were challenged with
      B16/F10 melanoma cells by subcutaneous inoculation on the back for the tumor
      growth model or by tail venous injection for the lung metastasis model.
      Development of subcutaneous tumor and lung metastasis was monitored by computed
      tomography scanning, which enabled accurate evaluation with the minimized
      sacrifice of mice. RESULTS: Vaccination with Tpit/E cells inhibited subcutaneous
      tumor growth and appearance of lung metastasis compared to control. Survival
      period was elongated in the Tpit/E vaccination in both of the two models. We also
      obtained hybridomas secreting specific antibodies to Tpit/E cells from a mouse
      vaccinated with the cells, indicating that specific immune response to the
      syngeneic endothelial cells was elicited. CONCLUSION: These results suggest that
      vaccination with an autologous endothelial cell line may be effective against
      melanoma.

PMID- 19183494
TI  - Single ventricle, bicuspid aorta and interatrial wall aneurysm as a rare complex
      adult congenital heart disease: a case report.
AB  - BACKGROUND: Single ventricle, bicuspid aortic valve and interatrial wall aneurysm
      in adulthood are a rare and unique case in medical literature. This presented
      case with congenital heart disease has never been treated surgically and clinical
      consequences seriously presented in adulthood. CASE PRESENTATION: A 27 year old
      man with complex congenital heart disease presented. At the age of six, the
      single ventricle was ultrasonographly diagnosed, but at age 27 clinical
      consequences started to be seriously present. We explored his history, clinical
      course, physical examination, laboratory findings, medical treatments and actual
      patient condition. CONCLUSION: The possibilities for surgical evaluation are
      presented.

PMID- 19183493
TI  - High prevalence of chronic kidney disease in Iran: a large population-based
      study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a global public health threat,
      associated with an alarming increase in morbidity and mortality. The importance
      is the worldwide increase in its incidence and prevalence. METHODS: In this cross
      sectional study, we estimate the prevalence and determine the associated factors
      of chronic kidney disease in a representative sample of 10063 participants aged
      over 20 years, in Tehran, Iran. Chronic kidney disease was defined as estimated
      glomerular filtration rate less than 60 mL/min/1.73 m2. Glomerular filtration
      rate was estimated from abbreviated prediction equation provided by the
      Modification of Diet in Renal Disease study (MDRD). RESULTS: Overall prevalence
      of CKD with the abbreviated MDRD equation was 18.9% (95% confidence interval (CI)
      18.2, 20.6). Age adjusted prevalence of CKD was 14.9% (95%CI 14.2, 15.6). Factors
      associated to CKD include age(years)(odds ratio(OR) 1.1, 95% CI 1.0 to 1.2),
      female gender (OR 3.1, 95% CI 2.6, 3.7), BMI (BMI 25 to <30 OR 1.5, 95% CI 1.3,
      1.8 and BMI > or = 30 OR 1.6, 95% CI 1.3, 2.0), high waist circumference (OR 1.2,
      95% CI 1.1, 1.4), hypertension (OR 1.2, 95% CI 1.1, 1.4), and dyslipidemia (OR
      1.3, 95% CI 1.1, 1.5). CONCLUSION: CKD with its high prevalence poses a definite
      health threat in Iran.

PMID- 19183495
TI  - Management of major bile duct injury after laparoscopic cholecystectomy: a case
      report.
AB  - INTRODUCTION: Bile duct injury is a severe and potentially life-threatening
      complication of laparoscopic cholecystectomy. Several series have described a
      0.5% to 0.6% incidence of bile duct injury during laparoscopic cholecystectomy.
      The aim of this study was to analyze the presentation, characteristics, related
      investigation, and treatment results of major bile duct injuries after
      laparoscopic cholecystectomy. CASE PRESENTATION: A rare case of a 48-year-old
      Greek woman with a triple bile duct injury (right and left hepatic duct ligation
      and common bile duct cross-section) is presented. A Roux en Y hepaticojejunostomy
      was performed after repeated endoscopic retrograde cholangiopancreatographies,
      percutaneous transhepatic catheterization of the ducts and magnetic resonance
      cholangiographies to delineate the biliary anatomy and assess the level of
      injury. CONCLUSION: Early recognition and an adequate multidisciplinary approach
      are the cornerstones for the optimal final outcome. Suboptimal management of
      injuries often leads to more extensive damage to the biliary tree and its
      vasculature. Early referral to a tertiary care center with experienced
      hepatobiliary surgeons and skilled interventional radiologists would appear to be
      necessary to assure optimal results.

PMID- 19183496
TI  - Quality management: reduction of waiting time and efficiency enhancement in an
      ENT-university outpatients' department.
AB  - BACKGROUND: Public health systems are confronted with constantly rising costs.
      Furthermore, diagnostic as well as treatment services become more and more
      specialized. These are the reasons for an interdisciplinary project on the one
      hand aiming at simplification of planning and scheduling patient appointments, on
      the other hand at fulfilling all requirements of efficiency and treatment
      quality. METHODS: As to understanding procedure and problem solving activities,
      the responsible project group strictly proceeded with four methodical steps:
      actual state analysis, analysis of causes, correcting measures, and examination
      of effectiveness. Various methods of quality management, as for instance opinion
      polls, data collections, and several procedures of problem identification as well
      as of solution proposals were applied. All activities were realized according to
      the requirements of the clinic's ISO 9001:2000 certified quality management
      system. The development of this project is described step by step from planning
      phase to inauguration into the daily routine of the clinic and subsequent control
      of effectiveness. RESULTS: Five significant problem fields could be identified.
      After an analysis of causes the major remedial measures were: installation of a
      patient telephone hotline, standardization of appointment arrangements for all
      patients, modification of the appointments book considering the reason for coming
      in planning defined working periods for certain symptoms and treatments,
      improvement of telephonic counselling, and transition to flexible time planning
      by daily updates of the appointments book. After implementation of these changes
      into the clinic's routine success could be demonstrated by significantly reduced
      waiting times and resulting increased patient satisfaction. CONCLUSION:
      Systematic scrutiny of the existing organizational structures of the outpatients'
      department of our clinic by means of actual state analysis and analysis of causes
      revealed the necessity of improvement. According to rules of quality management
      correcting measures and subsequent examination of effectiveness were performed.
      These changes resulted in higher satisfaction of patients, referring colleagues
      and clinic staff the like. Additionally the clinic is able to cope with an
      increasing demand for appointments in outpatients' departments, and the clinic's
      human resources are employed more effectively.

PMID- 19183497
TI  - Brain abscess formation as a CSF shunt complication: a case report.
AB  - The formation of a brain abscess as a result of a cerebrospinal fluid shunt
      complication is extremely rare in the literature with only 7 cases reported in
      the last 20 years. We report a patient that developed a brain abscess adjacent to
      a functioning ventricular catheter in the presence of shunt infection by another
      pathogen. Clinicians should consider this complication in any shunted patient
      with clinical features of infection and suggestive changes on imaging however
      subtle. Expedited standard management for the abscess and the CSF shunt
      infection, if present, should be employed. Removal of all non-functioning
      catheters should be encouraged.

PMID- 19183499
TI  - Scrotal metastases from colorectal carcinoma: a case report.
AB  - A 72-year-old man presented with a two month history of rectal bleeding.
      Colonoscopy demonstrated synchronous lesions at 3 cm and 40 cm with histological
      analysis confirming synchronous adenocarcinomata. He developed bilobar hepatic
      metastases while undergoing neoadjuvant chemoradiotherapy. Treatment was
      complicated by Fournier's gangrene of the right hemiscrotum which required
      surgical debridement. Eight months later he re-presented with an ulcerating
      lesion on the right hemiscrotum. An en-bloc resection of the ulcerating scrotal
      lesion and underlying testis was performed. Immunohistological analysis revealed
      metastatic adenocarcinoma of large bowel origin. Colorectal metastasis to the
      urogenital tract is rare and here we report a case of rectal carcinoma
      metastasizing to scrotal skin.

PMID- 19183500
TI  - Cutaneous larva migrans: a case report.
AB  - BACKGROUND: Cutaneous larva migrans may be diagnosed by the typical clinical
      presentation, consisting on a pruritic serpiginous lesion that advances in a
      patient with a history of sunbathing, walking barefoot on the beach, or similar
      activity in a tropical location. CASE PRESENTATION: We describe the case of a
      Mediterranean 32-year-old man, recently returned from a trip to a Brazilian
      beach, which presented with a 2-week history of pruritic cutaneous lesions that
      had not resolved after treatment with oral antihistamines and topical
      fluocinolone ointment. Physical examination showed a serpiginous, erythematous
      and slightly elevated lesion of 2-mm wide and 7-cm long located on the posterior
      aspect of his left knee. Patient affirmed that the lesion advanced progressively.
      Laboratory analyses only revealed an elevated absolute eosinophil count.
      Albendazole 400 mg/d 3 days was administered to the patient with complete
      resolution of symptoms within 1 week. CONCLUSION: Cutaneous larva migrans is
      common among travelers returning from tropical countries. We review epidemiology,
      clinical, diagnosis and therapeutic options of cutaneous larva migrans.

PMID- 19183498
TI  - Gut health immunomodulatory and anti-inflammatory functions of gut enzyme
      digested high protein micro-nutrient dietary supplement-Enprocal.
AB  - BACKGROUND: Enprocal is a high-protein micro-nutrient rich formulated
      supplementary food designed to meet the nutritional needs of the frail elderly
      and be delivered to them in every day foods. We studied the potential of Enprocal
      to improve gut and immune health using simple and robust bioassays for gut cell
      proliferation, intestinal integrity/permeability, immunomodulatory, anti
      inflammatory and anti-oxidative activities. Effects of Enprocal were compared
      with whey protein concentrate 80 (WPC), heat treated skim milk powder, and other
      commercially available milk derived products. RESULTS: Enprocal (undigested) and
      digested (Enprocal D) selectively enhanced cell proliferation in normal human
      intestinal epithelial cells (FHs74-Int) and showed no cytotoxicity. In a dose
      dependent manner Enprocal induced cell death in Caco-2 cells (human colon
      adencarcinoma epithelial cells). Digested Enprocal (Enprocal D: gut enzyme
      cocktail treated) maintained the intestinal integrity in transepithelial
      resistance (TEER) assay, increased the permeability of horseradish peroxidase
      (HRP) and did not induce oxidative stress to the gut epithelial cells. Enprocal D
      upregulated the surface expression of co-stimulatory (CD40, CD86, CD80), MHC I
      and MHC II molecules on PMA differentiated THP-1 macrophages in coculture
      transwell model, and inhibited the monocyte/lymphocyte (THP-1/Jurkat E6-1 cells)
      epithelial cell adhesion. In cytokine secretion analyses, Enprocal D down
      regulated the secretion of proinflammatory cytokines (IL-1beta and TNF-alpha) and
      up-regulated IFN-gamma, IL-2 and IL-10. CONCLUSION: Our results indicate that
      Enprocal creates neither oxidative injury nor cytotoxicity, stimulates normal gut
      cell proliferation, up regulates immune cell activation markers and may aid in
      the production of antibodies. Furthermore, through downregulation of
      proinflammatory cytokines, Enprocal appears to be beneficial in reducing the
      effects of chronic gut inflammatory diseases such as inflammatory bowel disease
      (IBD). Stimulation of normal human fetal intestinal cell proliferation without
      cell cytotoxicity indicates it may also be given as infant food particularly for
      premature babies.

PMID- 19183501
TI  - Active immunization using exotoxin A confers protection against Pseudomonas
      aeruginosa infection in a mouse burn model.
AB  - BACKGROUND: Pseudomonas aeruginosa is an important cause of nosocomial infection
      and may lead to septicemia and death. We evaluated the immunogenicity of semi
      purified exotoxin A from the bacterium in a mouse burn model. METHODS: The toxoid
      was prepared from exotoxin A taken from toxigenic strains of P. aeruginosa (PA
      103). 50 mice were immunized with the toxoid, burned with hot metal and infected
      with 1 x 10(8) CFU of toxigenic strains of P. aeruginosa (experimental group); 25
      non-immunized mice were also burned and infected (control group). The mortality
      rate and presence of any exotoxin and P. aeruginosa in the sera, liver and spleen
      were determined. RESULTS: In the experimental group, 2 mice died before the burns
      were administered and were excluded from the study. The remainder (48 mice) were
      challenged with a lethal dose of P. aeruginosa and followed for 70 days. 3 of
      these mice died. Neither P. aeruginosa nor exotoxin A was not detected in the
      liver, spleen or sera of the surviving mice. The protective efficacy of toxoid
      vaccination was therefore 93.8%. In the control group, all mice died from
      bacteremia and septicemia, most (80%) within 6 days, and P. aeruginosa and
      exotoxin A were isolated from sera, spleen and liver. CONCLUSION: Active
      immunization of mice using a semi-purified exotoxin A derived from P. aeruginosa
      was 93.8% effective at protecting mice from subsequent P. aeruginosa infections
      in a mouse burn model.

PMID- 19183503
TI  - Convergent and divergent patterns of morphological differentiation provide more
      evidence for reproductive character displacement in a wood cricket Gryllus
      fultoni (Orthoptera: Gryllidae).
AB  - BACKGROUND: In ecological character displacement, traits involved in reproductive
      isolation may not evolve in arbitrary directions when changes in these traits are
      by-products of adaptation to an ecological niche. In reproductive character
      displacement, however, selection acts directly on reproductive characters to
      enhance the degree of reproductive isolation between sympatric populations. Thus,
      the direction of change in reproductive characters may be arbitrary in relation
      to changes in other morphological characters. We characterized both tegminal
      characters and characters indicative of body size in sympatric and allopatric
      populations of Gryllus fultoni, a species displaying character displacement in
      its calling song characters in areas of sympatry with G. vernalis populations, to
      infer the nature and direction of selection acting on reproductive and
      morphological characters in sympatry. RESULTS: Except for mirror area, the number
      of teeth in a file, and ovipositor length of G. fultoni, all male and female
      morphological characters in G. fultoni and G. vernalis exhibited a uniform
      tendency to decrease in size with increasing latitude. There was no significant
      variation in female morphological characters between sympatric and allopatric G.
      fultoni populations. However, males of sympatric and allopatric G. fultoni
      populations significantly differed in head width, hind femur length, and mirror
      area even after controlling for clinal factors. Head width and hind femur length
      of G. fultoni were more similar to those of G. vernalis in sympatric populations
      than in allopatric populations, resulting in morphological convergence of G.
      fultoni and G. vernalis in sympatry. However, the mirror area of G. fultoni
      displayed the divergent pattern in relation to the sympatric G. vernalis
      populations. CONCLUSION: Divergence-enhancing selection may be acting on mirror
      area as well as calling song characters, whereas local adaptation or clinal
      effects may explain variation in other morphological characters in sympatric
      populations of G. fultoni. This study also suggests that structures and behaviors
      that directly enhance reproductive isolation may evolve together, independently
      of other morphological traits.

PMID- 19183502
TI  - Cocaine induces cell death and activates the transcription nuclear factor kappa-B
      in PC12 cells.
AB  - Cocaine is a worldwide used drug and its abuse is associated with physical,
      psychiatric and social problems. The mechanism by which cocaine causes
      neurological damage is very complex and involves several neurotransmitter
      systems. For example, cocaine increases extracellular levels of dopamine and free
      radicals, and modulates several transcription factors. NF-kappaB is a
      transcription factor that regulates gene expression involved in cellular death.
      Our aim was to investigate the toxicity and modulation of NF-kappaB activity by
      cocaine in PC 12 cells. Treatment with cocaine (1 mM) for 24 hours induced DNA
      fragmentation, cellular membrane rupture and reduction of mitochondrial activity.
      A decrease in Bcl-2 protein and mRNA levels, and an increase in caspase 3
      activity and cleavage were also observed. In addition, cocaine (after 6 hours
      treatment) activated the p50/p65 subunit of NF-kappaB complex and the
      pretreatment of the cells with SCH 23390, a D1 receptor antagonist, attenuated
      the NF-kappaB activation. Inhibition of NF-kappaB activity by using PDTC and
      Sodium Salicilate increased cell death caused by cocaine. These results suggest
      that cocaine induces cell death (apoptosis and necrosis) and activates NF-kappaB
      in PC12 cells. This activation occurs, at least partially, due to activation of
      D1 receptors and seems to have an anti-apoptotic effect on these cells.

PMID- 19183504
TI  - The effect of health and nutrition education intervention on women's postpartum
      beliefs and practices: a randomized controlled trial.
AB  - BACKGROUND: 'Sitting month' is the Chinese tradition for postpartum customs.
      Available studies indicate that some of the traditional postpartum practices are
      potentially harmful for women's health. However, no intervention study aiming at
      postpartum practices has been performed. In this paper we evaluated the effect of
      a health and nutrition education intervention, which focused on improving
      postpartum dietary quality and optimal health behaviors. METHODS: The study
      design was a randomized controlled trial conducted in both urban and rural area
      of Hubei between August 2003 and June 2004. A total of 302 women who attended the
      antenatal clinic during the third trimester with an uncomplicated pregnancy were
      recruited. Women randomized to the education intervention group in both urban and
      rural area received two two-hour prenatal education sessions and four postpartum
      counseling visits. Control group women received usual health care during
      pregnancy and postpartum period. Women were followed up until 42 days postpartum.
      Outcome measures were nutrition and health knowledge, dietary behavior, health
      behavior and health problems during the postpartum period. RESULTS: Women in the
      intervention groups exhibited significantly greater improvement in overall
      dietary behaviors such as consumption of fruits, vegetables, soybean and soybean
      products as well as nutrition and health knowledge than those in the control
      groups. Significantly more women in the intervention groups give up the
      traditional behavior taboos. The incidence of constipation, leg cramp or joint
      pain and prolonged lochia rubra was significantly lower in the intervention
      groups as compared with the control groups. CONCLUSION: The study shows that
      health and nutrition education intervention enable the women take away some of
      the unhealthy traditional postpartum practices and decrease the prevalence of
      postpartum health problems. The intervention has potential for adaptation and
      development to large-scale implementation. TRIAL REGISTRATION NUMBER:
      klACTRN12607000549426.

PMID- 19183505
TI  - Solitary anterior abdominal wall leiomyoma in a 31-year-old multipara woman: a
      case report.
AB  - BACKGROUND: Anterior abdominal wall fibroid are uncommon and could be a cause of
      pain and discomfort. Very few cases have been reported in the literature but none
      in our region. CASE PRESENTATION: We present an uncommon case of a 31 year old
      para 2+2 trader from the Itsekiri tribe of the Niger Delta region of Nigeria who
      presented with a one year history of a periumbilcal mass, had surgical removal of
      the mass and histology revealed leiomyoma. CONCLUSION: Abdominal wall fibroid is
      a good differential diagnosis to be considered in any woman of reproductive age
      with an anterior abdominal mass and previous uterine surgery, including
      laparoscopic surgeries.

PMID- 19183506
TI  - Survey of physician knowledge regarding antiretroviral medications in
      hospitalized HIV-infected patients.
AB  - BACKGROUND: Antiretroviral prescribing errors are common among hospitalized
      patients. Inadequate medical knowledge is likely one of the factors leading to
      these errors. Our objective was to determine the proportion of hospital
      physicians with knowledge gaps about prescribing antiretroviral medications for
      hospitalized HIV-infected patients and to correlate knowledge with length and
      type of medical training and experience. METHODS: We conducted an electronic
      survey comprising of ten clinical scenarios based on antiretroviral-prescribing
      errors seen at two community teaching hospitals. It also contained demographic
      questions regarding length and type of medical training and antiretroviral
      prescribing experience. Three hundred and forty three physicians at both
      hospitals were asked to anonymously complete the survey between February 2007 and
      April 2007. RESULTS: One hundred and fifty-seven physicians (46%) completed at
      least one question. The mean percentage of correct responses was 33% for resident
      physicians, 37% for attending physicians, and 93% for Infectious Diseases or HIV
      (ID/HIV) specialist physicians. Higher scores were independently associated with
      ID/HIV specialty, number of outpatients seen per month and physician reported
      comfort level in managing HIV patients (P < .001). CONCLUSION: Non-ID/HIV
      physicians had uniformly poor knowledge of common antiretroviral medication
      regimens. Involvement of ID/HIV specialists in the prescribing of antiretrovirals
      in hospitalized patients might mitigate prescribing errors stemming from
      knowledge deficits.

PMID- 19183508
TI  - Evaluation of quality of life related to nutritional status.
AB  - The way in which the quality of life related to health (HRQoL) is affected by the
      nutritional status of the patient is a subject of constant interest and permanent
      debate. The purpose of the present paper is to review those studies that relate
      HRQoL to nutritional status and examine the tools (questionnaires) that they use
      to investigate this relationship. A critical review of published studies was
      carried out via an investigation of the following databases: MEDLINE (via
      PubMed); EMBASE; The Cochrane Library; Cumulative Index to Nursing and Allied
      Health Literature (CINAHL); Institute for Scientific Information (ISI) Web of
      Science; Latin American and Caribbean Health Sciences Literature (LILACS);
      Spanish Health Sciences Bibliographic Index (IBECS). The search was carried out
      from the earliest date possible until July 2007.The medical subject heading terms
      used were 'quality of life', 'nutritional status' and 'questionnaires'. The
      articles had to contain at least one questionnaire that evaluated quality of
      life. Twenty-eight documents fulfilling the inclusion criteria were accepted,
      although none of them used a specific questionnaire to evaluate HRQoL related to
      nutritional status. However, some of them used a combination of generic
      questionnaires with the intention of evaluating the same. Only three studies
      selectively addressed the relationship between nutritional status and quality of
      life, this evaluation being performed not by means of specific questionnaires but
      by statistical analysis of data obtained via validated questionnaires.

PMID- 19183507
TI  - Lower extremity joint kinetics and lumbar curvature during squat and stoop
      lifting.
AB  - BACKGROUND: In this study, kinematics and kinetics of the lower extremity joint
      and the lumbar lordosis during two different symmetrical lifting techniques(squat
      and stoop) were examined using the three-dimensional motion analysis. METHODS:
      Twenty-six young male volunteers were selected for the subjects in this study.
      While they lifted boxes weighing 5, 10 and 15 kg by both squat and stoop lifting
      techniques, their motions were captured and analyzed using the 3D motion analysis
      system which was synchronized with two forceplates and the electromyographic
      system. Joint kinematics was determined by the forty-three reflective markers
      which were attached on the anatomical locations based on the VICON Plug-in-Gait
      marker placement protocol. Joint kinetics was analyzed by using the inverse
      dynamics. Paired t-test and Kruskal-Wallis test was used to compare the
      differences of variables between two techniques, and among three different
      weights. Correlation coefficient was calculated to explain the role of lower limb
      joint motion in relation to the lumbar lordosis. RESULTS: There were not
      significant differences in maximum lumbar joint moments between two techniques.
      The hip and ankle contributed the most part of the support moment during squat
      lifting, and the knee flexion moment played an important role in stoop lifting.
      The hip, ankle and lumbar joints generated power and only the knee joint absorbed
      power in the squat lifting. The knee and ankle joints absorbed power, the hip and
      lumbar joints generated power in the stoop lifting. The bi-articular antagonist
      muscles' co-contraction around the knee joint during the squat lifting and the
      eccentric co-contraction of the gastrocnemius and the biceps femoris were found
      important for maintaining the straight leg during the stoop lifting. At the time
      of lordotic curvature appearance in the squat lifting, there were significant
      correlations in all three lower extremity joint moments with the lumbar joint.
      Differently, only the hip moment had significant correlation with the lumbar
      joint in the stoop lifting. CONCLUSION: In conclusion, the knee extension which
      is prominent kinematics during the squat lifting was produced by the
      contributions of the kinetic factors from the hip and ankle joints(extensor
      moment and power generation) and the lumbar extension which is prominent
      kinematics during the stoop lifting could be produced by the contributions of the
      knee joint kinetic factors(flexor moment, power absorption, bi-articular muscle
      function).

PMID- 19183509
TI  - Functional food and nutraceutical registration processes in Japan and China: a
      diffusion of innovation perspective.
AB  - Purpose - This paper looks into the functional food and nutraceutical
      registration processes in Japan and China. The Japanese have developed the Foods
      for Specified Health Use (FOSHU) registration process whereas the Chinese have
      put into place the Health Food (HF) registration process. The aim of this paper
      is to compare the regulation processes between the two countries in search for
      answers to three core empirical questions: (1) how have the registration
      processes developed and changed? (2) What are the similarities and differences
      between the processes of registration in the two countries investigated? (3) Why
      are the registration processes similar/different? Method - The study was
      conducted using secondary sources. The literature surveyed covered academic
      journals, trade journals, magazine and newspaper articles, market reports,
      proceedings, books and web pages of relevant regulatory authorities and
      regulatory consultants. Information from the more recently published sources was
      used preferentially over older sources. As well as using the most recent sources,
      information was selected on the basis of which source it was from. Official
      regulations and SFDA and MHLW websites would contain accurate and up to date
      information and information from here would be taken as true over other sources
      of information. Results - The two diagrams of the registration processes
      respectively in Japan and China clearly show that there are similarities and
      differences. There are six categories under which these can be found: (1) the
      scientific evidence required; (2) the application process; (3) the evaluation
      process; (4) the law and the categories of products; (5) the labels and the types
      of claims; and finally (6) the cost and the time involved. Conclusions -The data
      analysis suggests that the process of diffusion of innovation played a role in
      the development of the regulations. Further it was found that while Japan was at
      the outset a pioneer innovator in nutraceutical registration processes, there are
      indications that in more recent years it too imitated other countries. NOVELTY
      STATEMENT: The assortment of regulatory regimes creates much uncertainty for the
      firms and the lack of familiarity and poor knowledge of the regulatory situation
      increases the risk of failure. The research presented in this paper provides
      highly valuable information to any biotech/pharmaceutical/nutraceutical companies
      developing their market entry strategy in Japan and China. There are few national
      and international studies of drug registration application processes but even
      fewer comparative studies of functional food and neutraceutical registration
      application processes such as this one and none using a diffusion of innovation
      perspective.

PMID- 19183510
TI  - Evidence for non-linear pharmacokinetics of oxytocin in anesthetizetized rat.
AB  - PURPOSE: Because oxytocin (OT) is potentially useful in cardiovascular therapy
      but has hormonal roles on the cardiovascular and renal systems, we characterized
      its pharmacokinetic (PK) properties as a function of dose. METHODS: A single
      intravenous bolus of OT was given at doses of 200, 300, 500, 1000, 3000, 5000 and
      10000 ng/kg to anesthetized male rats (n >= 4 per dose). Blood samples (6) were
      taken over 72 min to 150 min, depending on dose. The individual time-courses of
      plasma OT concentrations were analyzed with a one- or an open two-compartment PK
      model. Kruskal-Wallis tests (alpha=0.05) were used to compare the PK parameters
      among groups. RESULTS: At doses up to 500 ng/kg, OT showed a higher median
      systemic clearance (CLT = 0.0624 L/(min*kg); 0.0622 +/- 0.0228 as mean +/- SD
      value), a higher median central compartment volume of distribution (VC = 0.7906
      L/kg; 0.6961 +/- 0.1754), and a lower median elimination half life
      (t(1/2)(lambdaz) 7.94 min; 9.08 +/- 4.3) with respect to the higher doses (CLT =
      0.0266 L/(min*kg); 0.0284 +/- 0.0098, VC = 0.2213 L/kg; 0.2227 +/- 0.1142, and
      t(1/2)(lambdaz) 21.09 min; 28.36 +/- 21.8), all differences being significant (p
      0.0008). Minimal differences were found for the estimates of these PK parameters
      among the 4 higher OT doses. CONCLUSION: The PK properties and persistence of
      exogenous OT are not proportional to dose, therefore this must be accounted for
      in dosing regimen design for potential cardiovascular therapy.

PMID- 19183511
TI  - Effect of radical scavenger N-tert-butyl-alpha-phenylnitrone on stroke in a rat
      model using a telemetric system.
AB  - We used malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) as a
      stroke model to explore the effects of the radical scavenger N-tert-butyl-alpha
      phenylnitrone (PBN) on stroke. PBN was administrated in drinking water to M
      SHRSP. Circadian rhythms in heart rate, blood pressure, and locomotive activity
      in M-SHRSP were monitored with a telemetric system, in addition to measurement of
      water intake and body weight. Stroke-onset was assessed by changes in
      neurological symptoms, water intake, and body weight. Circadian rhythms were
      basically the same between PBN-treated and control rats several days after stroke
      onset. Significant differences were seen in blood pressure, relative weight of
      brain and water intake, heart rate, and locomotive activity between two groups.
      As a result, no significant difference in age of stroke onset was seen between
      PBN-treated and control rats, but PBN-treated rats displayed prolonged mean life
      spans. PBN might be effective in prolonging life span.

PMID- 19183512
TI  - A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered
      drug release.
AB  - PURPOSE: Controlled drug release, especially tumor-targeted drug release, remains
      a great challenge. Here, we prepare a novel fluoride anion-modified gelatin
      nanogel system and investigate its characteristics of ultrasound-triggered drug
      release. METHODS: Adriamycin gelatin nanogel modified with fluoride anion (ADM
      GNMF) was prepared by a modified co-precipitation method with fluoride anion and
      sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic
      agent adriamycin (ADM) were measured by high performance liquid chromatography
      (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and
      photo-correlation spectroscopy. The size distribution and drug release efficiency
      of ADM-GNMF, before and after sonication, were measured by two designed measuring
      devices that consisted of either a submicron particle size analyzer and an
      ultrasound generator as well as an ultrasound generator, automatic sampler, and
      HPLC. RESULTS: The ADM-GNMF was stable in solution with an average diameter of
      46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and
      6.38%, respectively. The ultrasound-triggered drug release and size change were
      most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min
      duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF
      was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm
      to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size
      in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF
      was released within 2~3 min without sonication, and only negligible size changes
      were found. CONCLUSIONS: The ADM-GNMF system efficiently released the encompassed
      drug in response to ultrasound, offering a novel and promising controlled drug
      release system for targeted therapy for cancer or other diseases.

PMID- 19183513
TI  - Inhibition of monosodium urate crystal-induced inflammation by withaferin A.
AB  - PURPOSE: Gouty arthritis is a characteristically intense acute inflammatory
      reaction resulting from the formation of sodium urate crystals in the joint
      cavity. In the present study, the effect of withaferin A, a steroidal lactone was
      investigated on monosodium urate crystal-induced inflammation in mice; an
      experimental model for gouty arthritis and compared it with that of the non
      steroidal anti-inflammatory drug, indomethacin. METHODS: Paw volume and
      levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status
      and inflammatory mediator TNF-alpha were determined in control and monosodium
      urate crystal-induced mice. The levels of beta-glucuronidase and lactate
      dehydrogenase were also measured in monosodium urate crystal-incubated
      polymorphonuclear leucocytes (PMNL). RESULTS: Paw volume, the levels of lysosomal
      enzymes, lipid peroxidation, and inflammatory mediator tumour necrosis factor
      alpha were found to be increased significantly and the activities of antioxidant
      status were in turn decreased in monosodium urate crystal-induced mice; however
      these changes were reverted back to near normal levels in withaferin A (30
      mg/kg/b.wt, i.p.) treated monosodium urate crystal-induced mice. In addition,
      beta-glucuronidase and lactate dehydrogenase level were reduced in withaferin A
      (100microg/ml) treated monosodium urate crystal-incubated polymorphonuclear
      leucocytes. CONCLUSION: The present findings clearly indicated that withaferin A
      exerted a strong anti-inflammatory effect against gouty arthritis.

PMID- 19183514
TI  - Exploitation of De Novo helper-lipids for effective gene delivery.
AB  - PURPOSE: In gene delivery, a fusogenic lipid such as dioleyl
      phosphatidylethanolamine (DOPE) which is a component of cationic liposomal vector
      is important factor for effective transfection efficiency. We investigated the
      effect of penetration enhancers as alternative helper-lipids to DOPE. METHODS:
      Transdermal penetraion enhancers such as N-lauroylsarcosine (LS), (R)-(+)
      limonene (LM), vitamin E (VE), and phosphatidyl choline from eggs (EggPC) were
      used in this experiments as helper-lipids with N-[1-(2, 3-dioleyloxy) propyl]-N,
      N, N-trimethlylammonium chloride (DOTMA) and cholesterol (CHOL). We examined in
      vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo
      transfection efficiency of plasmid DNA/cationic liposomes complexes. RESULTS: In
      transfection experiments in vitro, the cationic lipoplexes containing LS had
      highest transfection efficiency among the other lipoplexes independently of FBS.
      Furthermore, the lipoplexes containing LS had lowest cell toxicity among the
      other lipoplexes in the presence of FBS. As the results of erythrocytes
      interaction experiment, DOTMA/LS/CHOL, DOTMA/VE/CHOL, and DOTMA/EggPC/CHOL
      lipoplexes showed extremely lower hematotoxicity. On the basis of these results,
      the in vivo transfection efficiencies of the lipoplexes were examined. The
      lipoplexes containing LS had the highest transfection activity among the other
      lipoplexes. CONCLUSION: In conclusion, several transdermal penetration enhancers
      are available for alternative helper-lipids to DOPE in cationic liposomal
      vectors. Among them, DOTMA/LS/CHOL lipoplexes showed superior characteristics in
      in vitro transfection efficiency, cell toxicity, hematotoxicity, and in vivo
      transfection efficiency.

PMID- 19183515
TI  - Bioreduction of idarubicin and formation of ROS responsible for DNA cleavage by
      NADPH-cytochrome P450 reductase and its potential role in the antitumor effect.
AB  - PURPOSE: Idarubicin is a clinically effective synthetic anthracycline analog used
      in the treatment of several human neoplasms. Anthracyclines have the potential to
      undergo bioactivation by flavoenzymes to free radicals and thus exert their
      cytotoxic actions. In this study, our main objective was to investigate the
      possible involvement of NADPH-cytochrome P450 reductase in the bioreductive
      activation of idarubicin to DNA-damaging species. METHODS: A pBR322 plasmid DNA
      damage assay was used as a sensitive method for detecting strand breaks in DNA
      exposed to idarubicin in the presence of P450 reductase and cofactor NADPH under
      various incubation conditions. In addition, the rates of idarubicin reduction by
      P450 reductases purified from phenobarbital-treated rabbit liver, beef liver and
      sheep lung microsomes were determined by measuring NADPH oxidation at 340 nm.
      RESULTS: The plasmid DNA experiments demonstrated that idarubicin could undergo
      bioreduction by P450 reductase with the resulting formation of DNA strand breaks.
      The antioxidant enzymes SOD and catalase, and hydroxyl radical scavengers, DMSO
      and thiourea, afforded significant levels of protection against idarubicin
      induced DNA strand breaks. These findings suggested that DNA damage by idarubicin
      occurs through a mechanism which involves its redox cycling with P450 reductase
      to generate reactive oxygen species (ROS). The extent of DNA damage by idarubicin
      was found to increase with increasing concentrations of drug or enzyme as well as
      with increasing incubation time. The capacity of idarubicin to induce DNA damage
      under above incubation conditions was compared with that of a model compound,
      mitomycin C. Finally, enzyme assays carried out with purified P450 reductases
      revealed that idarubicin exhibited about two-fold higher rate of reduction than
      mitomycin C. CONCLUSION: Our findings implicated bioreduction of idarubicin by
      P450 reductase and subsequent redox cycling under aerobic conditions as being one
      mode of idarubicin action potentially contributing to its antitumor effect.

PMID- 19183516
TI  - Time series analysis of the clinical laboratory test result on chemotherapy for
      gastric cancer.
AB  - PURPOSE: Time series analysis may be helpful to estimate hematological data on
      gastric cancer patients who receive S 1, but untreated raw clinical data are not
      suitable for this approach. Hematological monitoring data interpolated by spline
      were analyzed by an attractor plot, which is a form of time series analysis.
      METHODS: Hematological data of three gastric cancer patients were interpolated by
      cubic spline. The leave-one-out cross validation method was carried out and an
      attractor plot was adopted to evaluate red blood count (RBC) data. RESULTS: Well
      predicted data, such as RBC, changed slightly; however, data with great
      deviation, such as the white blood count (WBC), were poorly predicted. The
      reaction of marrow function to chemotherapy was observable by spline
      interpolation of RBC data. Furthermore, an attractor plot clarified the tendency
      of the interpolated hematological monitoring data. CONCLUSIONS: It is suggested
      that spline interpolation is effective as a pretreatment to analyze clinical data
      from a time series.

PMID- 19183517
TI  - Antibacterial alkaloids from chelidonium majus linn (papaveraceae) against
      clinical isolates of methicillin-resistant Staphylococcus aureus.
AB  - PURPOSE: This study describes the antibacterial effect of extracts and compounds
      isolated from the aerial part of Chelidonium majus Linn. (Papaveraceae) acting
      against clinical strains of methicillin-resistant Staphylococcus aureus (MRSA).
      METHODS: The activities were evaluated by using the macrobroth dilution method
      and reported as the MICs/MBCs. RESULTS: Bioassay-guided fractionation of the most
      active extract from the aerial parts (EtOAc) led to the isolation of
      benzo[c]phenanthridine-type alkaloids 8-hydroxydihydrosanguinarine (hhS), 8
      hydroxydihydrochelerythrine (hhC), which were potently active against MRSA
      strains. CONCLUSIONS: The selective antibacterial activity reported in this paper
      for 8-hydroxylated benzo[c]phenanthridine-type alkaloids isolated from C.majus
      opens the possibility that they could be helpful for the developing of new
      antibacterial agents for treating the infection of MRSA which has created
      nosocomial problem worldwide.

PMID- 19183518
TI  - Foresight scanning: future directions of clinical and pharmaceutical research.
AB  - Foresight Scanning: Future Directions of Clinical and Pharmaceutical Research.
      Brian C. Foster, Therapeutic Products Directorate, Health Canada, Ottawa,
      Ontario, Canada ABSTRACT The Canadian Society for Pharmaceutical Sciences
      Satellite Symposium on Foresight Scanning, May 26 and 27, 2008, Nordegg, Alberta,
      Canada, focussed on the future directions of clinical and pharmaceutical
      research. The symposium brought together a group of clinicians, regulatory
      scientists, researchers and students to examine where clinical, pharmaceutical,
      and regulatory science might be in 10 to 15 years. Industry, regulatory,
      analytical, and clinical perspectives were presented and discussed, as well as
      the impact of exogenous (indirect) and endogenous (direct) change drivers.
      Unconditional funding was provided by Bayer HealthCare; they had no input on the
      direction of the meeting or selection of speakers. It was envisioned that the
      more important endogenous drivers may not be new information or changes in
      technology, policy, regulation, or health care delivery, but amplification of
      long-term underlying trends by emergence of new technologies, convergence of
      existing technologies or new communication and collaboration vehicles such as Web
      2.0.

PMID- 19183519
TI  - Operative debridement of diabetic foot ulcers.

PMID- 19183523
TI  - Caudate split for open and laparoscopic liver resections.

PMID- 19183524
TI  - Attracting surgical clerks to surgical careers: role models, mentoring, and
      engagement in the operating room.
AB  - BACKGROUND: Declining interest in careers in surgery among medical students has
      contributed to growing concerns about the surgical workforce. Although the
      medical student clerkship is likely to play an important role in shaping
      students' impressions of careers in surgery, little is known about the nature of
      this process. This study was designed to identify those aspects of the clerkship
      that are associated with medical students expressing an interest in surgery at
      the end of the clerkship. STUDY DESIGN: Medical students completed a survey at
      the end of the surgical clerkship assessing characteristics of the clerkship
      experience and students' level of interest in pursuing a career in surgery. The
      survey also included open-ended questions about students' reasons for having
      increased or decreased interest in surgery, which were systematically analyzed to
      complement quantitative findings. RESULTS: Students who sutured (p = 0.001),
      drove the camera (p = 0.01), stated that they felt involved in the operating room
      (p = 0.009), and saw residents (p = 0.03) and attendings (p = 0.0003) as positive
      role models were more likely to be interested in surgery. After adjusting for
      covariates, students who sutured in the operating room were 4.8 times as likely
      to be interested in surgery (95% CI, 1.5 to 14.9) and students who drove the
      camera were 7.2 times as likely to be interested in surgery (95% CI, 1.1 to
      46.8). CONCLUSIONS: Students who participate actively in the operating room and
      those who are exposed to positive role models are more likely to be interested in
      pursuing a career in surgery. To optimize students' clerkship experiences and
      attract top candidates to the field of surgery, clerkship directors should
      encourage meaningful engagement of students in the operating room and facilitate
      mentoring experiences.

PMID- 19183525
TI  - Modern management of complex open abdominal wounds of war: a 5-year experience.
AB  - BACKGROUND: Optimal management of the open abdomen remains controversial. STUDY
      DESIGN: Retrospective review of patients injured during Operations Enduring
      Freedom and Iraqi Freedom returning to Walter Reed Army Medical Center (WRAMC)
      from January 2003 to October 2007 for treatment of open abdomen. RESULTS: Three
      hundred fifty-four patients were evacuated to WRAMC after laparotomy, including
      86 patients (24%) with open abdomen. Three transferred patients were excluded.
      Eighty-three patients, mean age 26 years (range 18 to 54 years), sustaining
      injury from secondary blast (n = 47), gunshot (n = 29), and blunt trauma (n = 7)
      were studied. Surgical management included early definitive abdominal closure
      (EDAC, n = 56; 67%), primary fascial closure (n = 15; 18%), planned ventral
      hernia (PVH, n = 9; 11%) and vacuum-assisted closure with AlloDerm (n = 3; 4%).
      EDAC closure involves serial closure with Gore-Tex Dualmesh and final closure
      supplemented with polypropylene mesh (62%) or AlloDerm (31%). There was no
      substantial difference in injury mechanism, age, length of evacuation to WRAMC,
      or Injury Severity Score (average 30) according to closure type. Complications
      included removal of infected prosthetic mesh in 4 EDAC closure patients (5%).
      Overall morbidity was lowest (60%) in primary repair patients (p = 0.01). Rates
      of deep venous thrombosis, pulmonary embolism, abdominal wall hematoma, and
      infection did not differ between groups. Fistula rate was increased with PVH
      (20%). Two patients with PVH died. PVH and EDAC mesh complications have been
      minimized in the last 2 years of the study. CONCLUSIONS: Primary closure of
      fascia is ideal but not always possible. Early definitive closure has avoided
      PVH. Mesh-related complications have decreased with time.

PMID- 19183526
TI  - Surgical site infection prevention: the importance of operative duration and
      blood transfusion--results of the first American College of Surgeons-National
      Surgical Quality Improvement Program Best Practices Initiative.
AB  - BACKGROUND: Surgical site infections (SSI) continue to be a significant problem
      in surgery. The American College of Surgeons-National Surgical Quality
      Improvement Program (ACS-NSQIP) Best Practices Initiative compared process and
      structural characteristics among 117 private sector hospitals in an effort to
      define best practices aimed at preventing SSI. STUDY DESIGN: Using standard NSQIP
      methodologies, we identified 20 low outlier and 13 high outlier hospitals for SSI
      using data from the ACS-NSQIP in 2006. Each hospital was administered a process
      of care survey, and site visits were conducted to five hospitals. Comparisons
      between the low and high outlier hospitals were made with regard to patient
      characteristics, operative variables, structural variables, and processes of
      care. RESULT: Hospitals that were high outliers for SSI had higher trainee-to-bed
      ratios (0.61 versus 0.25, p < 0.0001), and the operations took significantly
      longer (128.3+/-104.3 minutes versus 102.7+/-83.9 minutes, p < 0.001). Patients
      operated on at low outlier hospitals were less likely to present to the operating
      room anemic (4.9% versus 9.7%, p=0.007) or to receive a transfusion (5.1% versus
      8.0%, p=0.03). In general, perioperative policies and practices were very similar
      between the low and high outlier hospitals, although low outlier hospitals were
      readily identified by site visitors. Overall, low outlier hospitals were smaller,
      efficient in the delivery of care, and experienced little operative staff
      turnover. CONCLUSIONS: Our findings suggest that evidence-based SSI prevention
      practices do not easily distinguish well from poorly performing hospitals. But
      structural and process of care characteristics of hospitals were found to have a
      significant association with good results.

PMID- 19183527
TI  - Surgeon knowledge, behavior, and opinions regarding intraoperative
      cholangiography.
AB  - BACKGROUND: The risk of common bile duct injury during laparoscopic
      cholecystectomy (LC) is 50% to 70% lower when an intraoperative cholangiogram
      (IOC) is used, and this effect is exaggerated among less experienced surgeons.
      Routine IOC is not universal, and barriers to its use, including surgeon
      knowledge, behavior, and attitudes, should be understood in developing quality
      improvement interventions aimed at increasing IOC use. STUDY DESIGN: There were
      4,100 general surgeons randomly selected from the American College of Surgeons
      who were mailed a survey about IOC. Surveys with a valid exclusion (retired, no
      LC experience) were considered responsive but were excluded from data analysis.
      RESULTS: Forty-four percent responded, with 1,417 surveys analyzed (mean age
      51.8+/-9.6 years; 89.2% men; 55.3% private practice). Twenty-seven percent of
      respondents defined themselves as routine IOC users and 91.3% of routine users
      reported IOC use in more than 75% of LCs performed. Academic surgeons were less
      often routine users compared with nonacademics (15% versus 30%; p < 0.001).
      Selective users were more often low-volume (less than 20 LC/year) surgeons (8%
      versus 15%) as compared with routine users, who were more often high-volume (more
      than 100 LC/year) surgeons (27% versus 20%). Routine users had more favorable and
      accurate opinions about IOC (less costly and more protective of injury) than did
      selective users. Thirty-nine percent of routine users thought IOC decreased the
      risk of common bile duct injury by at least half compared with 10% of selective
      users. CONCLUSIONS: Surgeons at greatest risk for causing common bile duct injury
      (inexperienced, low-volume surgeons) and those who have the greatest opportunity
      to train others are less likely to use IOC routinely. These represent target
      groups for quality-improvement interventions aimed at broader IOC use.

PMID- 19183528
TI  - Regionalization of hepatic resections is associated with increasing disparities
      among some patient populations in use of high-volume providers.
AB  - BACKGROUND: The goal of our study was to determine the temporal trends in
      provider volume for liver resection procedures. STUDY DESIGN: The Nationwide
      Inpatient Sample database for 1988 through 2003 was used to determine temporal
      trends in hospital and surgeon volume of liver resection procedures. We also
      examined whether these trends in provider volume were associated with any changes
      in postoperative outcomes or in patients' access to high-volume providers.
      RESULTS: Regionalization of liver resection procedures to high-volume surgeons
      and hospitals has been occurring since 1988 and, in the most recent time period
      assessed, 25.8% of patients underwent hepatic resection by high-volume surgeons
      (> or = 17 procedures per year) and 29.9% of patients underwent resection in high
      volume hospitals (> or = 45 procedures per year). Unadjusted mortality data
      suggest that these trends might be associated with a strengthening of the inverse
      relationship between hospital volume of hepatic resection and postoperative
      mortality and with an increasing disparity for some patient populations in use of
      high-volume hospitals. CONCLUSIONS: Regionalization of liver resections is
      occurring at both the level of the individual surgeon and the hospitals where
      these procedures are performed. These trends in provider volume might be
      associated with increasing discrepancies in outcomes and patient demographics
      among different volume categories of hospitals.

PMID- 19183529
TI  - Laparoscopic management of choledochal cysts: technique and outcomes--a
      retrospective study of 35 patients from a tertiary center.
AB  - BACKGROUND: Choledochal cysts are congenital dilations of the biliary tree. The
      accepted mode of treatment is total excision with hepaticojejunostomy. In this
      retrospective study, we present our technique and results of laparoscopic
      choledochal cyst excision. STUDY DESIGN: We retrospectively studied 35 patients
      who had undergone laparoscopic choledochal cyst excision in our institute from
      1996 to 2008. Data about age, gender, type of choledochal cyst, symptoms,
      surgical technique, conversion rate, morbidity, and mortality were analyzed.
      RESULTS: There were Type 1B choledochal cysts in 27 patients (77%) and Type IVA
      in 8 patients (23%). An anomalous pancreatobiliary junction was found in 40%.
      Mean operative time was 295 minutes. Total cyst excision could be done in 26
      patients. The conversion rate in our series was 8.5%. The overall morbidity rate
      was 14.3%, the reoperation rate was 8.5%, the mortality rate was 0%, and the
      incidence of carcinoma was 8.5%. CONCLUSIONS: To minimize the risk of malignancy,
      total excision of the cyst is ideal, but a small proximal cuff of cyst is
      retained for small-size ducts to aid in the hepaticojejunostomy anastomosis. A
      slit on one end of the small ducts will render the anastomosis in an oblique
      orientation, widening the lumen. Dissecting the posterior cyst wall from the
      underlying portal vein is the most crucial part of the procedure. Morbidity and
      mortality rates after laparoscopic management are comparable with published
      results of the open procedure. Laparoscopic surgery for choledochal cysts is
      feasible, safe, and even advantageous.

PMID- 19183530
TI  - Advanced donor age alone does not affect patient or graft survival after liver
      transplantation.
AB  - BACKGROUND: Individuals greater than 60 years old donate an important portion of
      the organs available for orthotopic liver transplantation (OLT), but use of
      donors in this age group remains controversial. We hypothesized that proper
      selection of donors older than age 60 would not disadvantage recipients in terms
      of patient and graft survival. STUDY DESIGN: All OLTs performed at our center
      between January 1, 1990, and July 31, 2007, were divided into groups based on
      donor age: donors 60 years old or more and donors less than 60 years old.
      Recipients in each group were compared based on graft and patient survival at 1,
      3, and 5 years, Model for End-Stage Liver Disease (MELD) scores, cold ischemic
      times, and era of transplant (before or after 2001). RESULTS: There were 741
      recipients who met inclusion criteria. Ninety-one patients received livers from
      donors 60 years old or older, and 650 patients had donors younger than 60 years
      old. Overall patient survival rates in the group using donors 60 or older were
      86.8%, 72.6%, and 67.6% at 1, 3, and 5 years, respectively, and did not differ
      significantly from survival in the group receiving transplants from donors less
      than 60 (87.1%, 81.8%, and 75.5%; p=0.39). The 1-, 3-, and 5-year graft survivals
      in patients receiving transplants from donors 60 or older were 82.4%, 65%, and
      62.5%, respectively, and were not significantly different from those in the group
      using donors younger than 60 (84%, 78.6%, and 72.3%, respectively; p=0.39).
      Neither patient survival nor graft survival in recipients of organs from donors
      60 or older was affected by Model of End-Stage Liver Disease score. Recipients of
      older-donor livers had improved outcomes after 2001, which correlated with
      significant improvements in cold ischemic times. CONCLUSIONS: Our data suggest
      that age alone does not adversely affect recipient outcomes. When properly
      selected, donors older than 60 represent an important and safe increase in the
      liver donor pool.

PMID- 19183531
TI  - Is it necessary to harvest additional lymph nodes after resection of the most
      radioactive sentinel lymph node in breast cancer?
AB  - BACKGROUND: No consensus exists about the number of sentinel lymph nodes (SLNs)
      that should be removed based on radioactivity counts in breast cancer, although
      the "10% rule" is often used. We hypothesized that the node with the highest
      radioactivity would have the strongest probability of being a positive SLN, and
      we sought to determine the lowest radioactive count of a node harboring cancer.
      STUDY DESIGN: We retrospectively studied 332 breast cancer patients who underwent
      lymphoscintigraphy by injection of technetium 99m-labeled thiosulfate colloid and
      sentinel lymphadenectomy (SL) between 1997 and 2006, with intraoperative
      determination of radioactive counts of nodes by a gamma probe. All SLNs were
      examined by permanent sections consisting of at least 3 levels of 40- to 100-mum
      intervals for hematoxylin and eosin evaluation, with or without
      immunohistochemical staining for cytokeratins. RESULTS: Seventy-four percent of
      patients had more than 1 SLN removed (mean 2.8 per patient); 23.5% had SLN
      metastasis. Of the node-positive patients, the hottest SLN was positive in 85.9%
      (67 of 78). Five of the 78 patients (6.4%) with positive nodes had counts less
      than 10% of those of the hottest node. The lowest radioactive count of a positive
      SLN was 4.2% of that of the hottest node. Lymphatic mapping based on the 10% rule
      could greatly improve the false-negative rates compared with removing only the
      hottest SLN (14.1% versus 6.4%). CONCLUSIONS: Most positive SLNs had the highest
      radioactivity. Our institutional experience indicates that to obtain an
      acceptable false-negative rate, nodes should be removed until the 10% rule is
      met.

PMID- 19183532
TI  - Sexual dysfunction is common in the morbidly obese male and improves after
      gastric bypass surgery.
AB  - BACKGROUND: There has been limited research examining the mechanisms and
      epidemiology of sexual dysfunction in the morbidly obese. Our objectives were to
      measure sexual function in the morbidly obese man before and after substantial
      weight loss induced by gastric bypass surgery. STUDY DESIGN: All male patients in
      undergoing gastric bypass completed the Brief Male Sexual Function Inventory
      (BSFI) before and after operation. BSFI scores were also compared with published
      normative controls and analyzed for predictors of change. Mixed models were
      created to control for age, diabetes, and hypertension. RESULTS: Ninety-seven men
      with a mean age of 48 years (range 19 to 75 years) and mean body mass index of 51
      kg/m(2) (range 36 to 89 kg/m(2)) underwent gastric bypass surgery. On average,
      preoperative morbidly obese patients reported a substantially greater degree of
      sexual dysfunction than did published reference controls in all domains, p <
      0.001. Increasing weight independently predicted lower domain scores. Mean
      postoperative followup length was 19 months (range 6 to 45 months). On average,
      BSFI scores improved from preoperative levels by bivariate analysis in all
      categories (means+/-SE): sexual drive (range 0 to 8), 3.9+/-0.3 to 5.3+/-0.3;
      erectile function (range 0 to 12), 6.4+/-0.5 to 8.9+/-0.5; ejaculatory function
      (range 0 to 8), 4.9+/-0.4 to 6.3+/-0.4; problem assessment (range 0 to 12), 7.4+/
      0.5 to 9.6+/-0.5; and sexual satisfaction (range 0 to 4), 1.6+/-0.2 to 2.3+/-0.2;
      all p < 0.01. On multivariable analysis, the amount of weight loss independently
      predicted the degree of improvement in all BSFI domains, p < 0.05. After an
      average 67% excess weight loss, BSFI scores in postoperative gastric bypass
      patients approached those of the reference controls. CONCLUSIONS: Men with morbid
      obesity commonly suffer from profound, but reversible sexual dysfunction.

PMID- 19183533
TI  - Design and impact of an intraoperative pathway: a new operating room model for
      team-based practice.
AB  - BACKGROUND: The concept of a team-based model for delivery of care has been
      critical at our institution for improving efficiency and safety. Despite these
      measures, difficulties continue to occur during lengthy operating room
      procedures. Using a novel team-based practice model, a multidisciplinary team was
      organized to improve efficiency in microsurgical breast reconstruction. We
      describe development of an intraoperative pathway for deep inferior epigastric
      perforator (DIEP) flap breast reconstruction and its impact on various outcomes.
      STUDY DESIGN: We evaluated 150 patients who underwent DIEP flap breast
      reconstruction at Beth Israel Deaconess Medical Center from 2005 to 2008. Patient
      groups were subdivided into 50 unilateral and 50 bilateral procedures before the
      intraoperative pathway and 25 unilateral and 25 bilateral procedures after.
      Outcomes measured included operative time, complications, operating room and
      hospital costs, proper administration of prophylactic antibiotics and heparin,
      and staff satisfaction surveys. RESULTS: Mean operative times decreased after
      pathway implementation in both unilateral (8.2 hours to 6.9 hours; p < 0.001) and
      bilateral groups (12.8 hours to 10.6 hours; p < 0.001) and complication rates
      were unchanged. Mean operating room costs decreased in the unilateral group by
      10.2% (p = 0.018). Prophylactic heparin administration showed substantial
      improvements, although antibiotic administration and redosing of antibiotics
      trended upward. Staff surveys showed improved interdisciplinary communication,
      transition guidelines, and enhanced efficiency through standardization.
      CONCLUSIONS: Implementation of an intraoperative pathway led to improvements in
      operative time, cost, quality measures, and staff satisfaction. Refinement of the
      pathway with team resolution of variances might continue to improve outcomes.
      Complex, multi-team procedures can derive benefits from standardization and
      intraoperative pathway development.

PMID- 19183534
TI  - Proposed staging system for colon carcinoid tumors based on an analysis of 2,459
      patients.
AB  - BACKGROUND: Colon carcinoid remains an uncommon finding during screening
      endoscopy or operation, with little known about the longterm prognosis. The
      reason for this uncertainty is that no staging system exists to appropriately
      risk stratify or follow these patients for overall survival. We sought to
      investigate prognostic factors associated with colon carcinoid tumors and create
      a predictive staging system to accurately estimate prognosis. STUDY DESIGN: A
      search of the National Cancer Institute's Surveillance, Epidemiology, and End
      Results (SEER) database identified 15,983 patients with carcinoid tumors, with
      2,459 from the colon, from 1973 to 2004. Patients were analyzed to various
      clinicopathologic factors and a tumor (T1, T2, T3), lymph node (N0, N1), and
      metastasis (M0, M1) staging system was created according to these parameters.
      RESULTS: Of the 2,459 patients, 1,287 (52%) women and 1,172 (48%) men were
      identified, with a median age of 63 years (range, 12 to 96 years). Lymph node
      metastasis was found in 820 (48%), and distant metastatic disease was present in
      522 (24%) patients. On multivariate analysis, age, size, depth of invasion, lymph
      node involvement, distant metastasis, and location were significant. Four stages
      were created to statistically significant prognostic factors: 13% into stage I,
      32% into stage II, 12% into stage III, and 43% into stage IV. Five-year survival
      rates were 97%, 69%, 21%, and 17% for stages I through IV (p = 0.001).
      CONCLUSIONS: The newly developed TNM staging system accurately discriminates
      prognosis for carcinoid tumors of the colon. Incorporation of this staging system
      into clinical practice will allow better study of outcomes and development of
      stage-specific treatment recommendations.

PMID- 19183535
TI  - Quantitating the impact of stage migration on staging accuracy in colorectal
      cancer.
AB  - BACKGROUND: The number of nodes retrieved is a powerful predictor of survival in
      node-negative colorectal cancer (CRC). Whether this is because of improved
      staging or improved surgery, or both, is unclear. We sought to quantitate the
      impact of stage migration in node-negative colorectal cancer. STUDY DESIGN:
      Between January 1994 and December 2003, 7,192 patients in Region 5 of the
      California Cancer Registry, diagnosed with node-negative or node-positive
      colorectal cancer, were reviewed. The number of nodes examined, node-positive
      rate, and disease-specific survival (DSS) were analyzed. RESULTS: The mean number
      of nodes examined was 9.3 (range 0 to 89 nodes). The 5-year DSS was 84.5% for N0,
      65.2% for N1, and 46.8% for N2 disease. The 5-year DSS difference for those who
      had more than 12 nodes retrieved was 87.3% (95% CI, 85.2% to 89.3%) and for those
      with 0 to 3 nodes retrieved, 83.7% (95% CI, 80.6% to 86.82%; p = 0.0009). As the
      number of retrieved nodes increased, the risk of understaging patients decreased.
      For 0 to 3 nodes, 78.3% of patients were N0; for 4 to 7 nodes, 67.6%; 8 to 9
      nodes, 62.1%; 10 to 12 nodes, 59.5%; and only 57.2% for more than 12 nodes
      examined. Using more than 12 nodes as the definition of an adequate
      lymphadenectomy and staging, for apparently N0 patients with 0 to 3 nodes
      retrieved, DSS survival would be affected by approximately 5%. CONCLUSIONS:
      Differences in outcomes between CRC patients with limited numbers of nodes
      harvested and those with more than 12 nodes harvested are substantial. Stage
      migration alone can explain the entire DSS difference between patients with more
      than 12 nodes retrieved and those with smaller numbers of nodes retrieved.

PMID- 19183536
TI  - Surgeon-dependent predictive factors for mortality after elective colorectal
      resection and immediate anastomosis for cancer or nonacute diverticular disease:
      multivariable analysis of 2,605 patients.
AB  - BACKGROUND: Multivariable analysis best identifies independent risk factors.
      STUDY DESIGN: We conducted a prospective evaluation of 2,605 patients through
      univariate analysis followed by nonconditional multiple logistic regression
      analysis on 39 pre-, intra-, and postoperative factors, analyzed according to
      preoperative factors alone, preoperative and intraoperative factors together, and
      all 3 combined. The purpose was to identify surgeon-dependent independent risk
      factors for mortality after elective colorectal surgery, with immediate
      anastomosis for cancer and nonacute diverticular disease. RESULTS: Overall
      mortality was 3.5%. Through multivariable analysis, five risk factors were found
      when preoperative data were analyzed alone. Four remained (age between 60 and 75
      years, age greater than 75 years, male gender, and heart failure) and 4 new
      factors (palliative resection, total colectomy, respiratory failure, and surgeon
      dependent fecal soiling [the only surgeon-dependent factor]) appeared when pre-
      and intraoperative factors were analyzed together. Of the latter, two remained
      stable when all three categories of risk factors were combined and analyzed
      (palliative resection and total colectomy), and the two others disappeared. Of
      the eight pre-, intra-, and postoperative factors combined, two new factors
      appeared: extrasurgical site (ESS) and surgeon-dependent, organ space surgical
      site (O/SSS) morbidity. CONCLUSIONS: Every effort must be made to collect
      specific, surgeon-dependent (technical and clinical) data, along with
      administrative data, for multivariable analysis of risk factors. Classification
      into three periods (pre-, pre- and intraoperative together, and pre-, intra-, and
      postoperative combined) enables determination of relevant, surgeon-dependent risk
      factors (fecal soiling and postoperative morbidity) for which there are direct
      preventive actions.

PMID- 19183537
TI  - Utility of the endovascular stapler for right-sided laparoscopic donor
      nephrectomy: a 7-year experience at Mayo Clinic.
AB  - BACKGROUND: Management of the renal vasculature during right laparoscopic donor
      nephrectomy (LDN) to maximize vessel length has been controversial. The
      endovascular gastrointestinal anastomosis (GIA) stapler has been used for renal
      vascular control for our donors since the inception of our LDN program. We
      evaluated and compared the outcomes of right and left LDNs using a single method
      for hilar control. STUDY DESIGN: A retrospective review was performed of the
      first 400 LDNs and respective recipients at our institution. Patient
      demographics, perioperative variables, graft function, and complications were
      analyzed. RESULTS: Four hundred LDNs were performed between 1999 and 2007. Forty
      one were on the right. There were no statistically significant differences
      between the donor groups or their respective recipients. There were 4 (1%)
      stapler malfunctions, all occurring on the left side; 2 of these procedures were
      converted to open to obtain hemostasis. There were nearly equal rates of vascular
      complications, 4.9% and 4.7%, in the right and left groups, respectively. The
      overall immediate graft failure rate was 2.3%. Right and left recipient
      creatinine levels up to 24 months demonstrated no statistically significant
      differences. CONCLUSIONS: We propose that the endovascular GIA stapler for left
      and right laparoscopic donor nephrectomy is safe for the donor. It standardizes
      the process, minimizes the need for additional maneuvers in securing the renal
      hilum, and produces similar outcomes for the recipient. The transplant team also
      plays an equally large role in favorable graft outcomes.

PMID- 19183538
TI  - Risk factors for prolonged length of stay after urologic surgery: the National
      Surgical Quality Improvement Program.
AB  - BACKGROUND: Length of stay (LOS) is important, particularly as a marker for
      medical resource consumption. Determining which factors increase LOS can provide
      information on reducing costs and improving delivery of care. The objective of
      the current study was to identify patient preoperative and intraoperative risk
      factors for prolonged LOS after common urologic procedures. STUDY DESIGN:
      Beginning in 2003, a trained surgical reviewer from the University of Michigan
      used National Surgical Quality Improvement Program protocols to abstract clinical
      data from urology surgery patients. Data were manually collected and then
      transmitted through the Internet to a secure National Surgical Quality
      Improvement Program Web site. Five hundred fifty-six patients were accrued
      between December 2003 and December 2004. Multiple variable logistic regression
      analysis was used to identify preoperative and intraoperative factors associated
      with prolonged LOS, defined as LOS > or = 75(th) percentile (in days) for each
      procedure category based on data from the Nationwide Inpatient Sample. RESULTS:
      Overall, 7.3% of patients experienced prolonged LOS after urologic surgery. A
      history of previous cardiac surgery was the strongest independent predictor of
      prolonged LOS (odds ratio = 3.55; 95% CI, 1.60 to 7.74). Intraoperative process
      measures were also associated with prolonged LOS after common urologic
      procedures. CONCLUSIONS: In this sample of urologic patients, prolonged LOS is
      associated with both preoperative and intraoperative factors. Preoperative
      factors, such as previous cardiac surgery and abnormal creatinine and hematocrit,
      were independently associated with a prolonged LOS and interoperative processes,
      such as length of operation and intraoperative transfusion. To help reduce costs
      and improve the quality of urologic care, efforts should be made to improve
      intraoperative processes and to minimize preoperative risk factors.

PMID- 19183539
TI  - Anal dysplasia in kidney transplant recipients.
AB  - BACKGROUND: Although the risk of anal cancer in immunosuppressed individuals is
      significantly higher than in the general population, methods for detecting
      precancerous anal dysplasia have not been well studied in solid-organ transplant
      recipients. We sought to identify the incidence of anal dysplasia in kidney
      transplant recipients and associated factors that increase the likelihood of
      dysplasia. STUDY DESIGN: We prospectively analyzed kidney transplant recipients
      who had been immunosuppressed for at least 6 months with a functioning allograft.
      We interviewed willing participants and performed anal cytology sampling and high
      resolution anoscopy; if we found microscopic abnormalities, we performed
      biopsies. We used univariate analysis to measure the association between
      variables and anal dysplasia. RESULTS: Of the 40 participants, 15 were women and
      25 were men; their mean age was 61 years. Their median duration of
      immunosuppression was 5.6 years; 23 (59%) had fewer than 5 lifetime sexual
      partners, and 2 (5%) reported ever practicing anal intercourse. Of all cytology
      specimens, 35 (88%) had sufficient cells for interpretation and 2 (6%)
      demonstrated dysplasia. We performed biopsies in 11 patients; 6 had dysplasia (4
      low-grade, 2 high-grade). Of these patients, five had normal anal cytology. The
      sensitivity of cytology to predict histologic evidence of dysplasia was 17%.
      Overall, seven (18%) had dysplasia according to either cytology or histology
      specimens; two (5%) had high-grade dysplasia. We found no significant
      associations between the tested variables and the presence of dysplasia.
      CONCLUSIONS: A significant proportion of kidney transplant recipients harbor anal
      dysplasia. One time anal cytology sampling was not predictive of histologic
      findings. Although these findings confirm their high risk for dysplasia, a larger
      sample is required to more accurately quantify risk factors for dysplasia and
      progression to cancer.

PMID- 19183540
TI  - Secondary aortoenteric fistulas versus paraprosthetic erosions: is bleeding
      associated with a worse outcome?
AB  - BACKGROUND: Direct communication between an aortic prosthesis and the
      gastrointestinal (GI) tract may present with GI bleeding (aortoenteric fistulas
      [AEF]) or be incidental to a graft infection (paraprosthetic erosions [PPE]). The
      purposes of this study were to compare the outcomes of AEF versus PPE and to
      determine predictors of mortality associated with these lesions. STUDY DESIGN:
      Since 1992, 38 patients (23 men, 15 women; mean age 67 years) presented with AEF
      (n=16) or PPE (n=22). RESULTS: After complete graft excision, 26 patients (8 AEF,
      18 PPE) underwent in situ revascularization using femoral vein (n=24) or rifampin
      soaked prosthetic graft (n=2); 12 (8 AEF, 4 PPE) underwent extraanatomic bypass.
      There was no significant difference in mortality for AEF versus PPE (38% versus
      36%). Postoperative complications developed in 25 (66%) patients, including 10
      (26%) with GI complications requiring reintervention (5 colon necrosis, 5
      duodenal bleed or leak). There were no differences between AEF and PPE in
      operative transfusions, operative times, GI complications, ICU stay, hospital
      stay, or final discharge status. Multivariate stepwise logistic regression
      analysis revealed that GI complications (odds ratio [OR], 52.5; 95% CI, 3.5 to
      781; p=0.004) and age (OR, 1.2; 95% CI, 1.02 to 1.3; p=0.026) were the only
      independent predictors of in-hospital mortality. CONCLUSIONS: Surgical management
      of AEF and PPE should be tailored to patient illness and the extent of graft
      infection. Mortality from both lesions is dependent on patient and technical
      factors, not on the mode of presentation.

PMID- 19183541
TI  - Association of hypertension, diabetes, dyslipidemia, and metabolic syndrome with
      obesity: findings from the National Health and Nutrition Examination Survey, 1999
      to 2004.
AB  - BACKGROUND: Hypertension, diabetes, and dyslipidemia are common conditions
      associated with obesity. This study provides current estimates of the prevalence
      of hypertension, diabetes, dyslipidemia, and metabolic syndrome according to the
      severity of obesity in men and women participating in the 1999 to 2004 National
      Health and Nutrition Examination Survey (NHANES). STUDY DESIGN: Data from a
      representative sample of 13,745 US men and women who participated in the NHANES
      between 1999 and 2004 were reviewed. Overweight and obesity classes 1, 2, and 3
      were defined as a body mass index of 25.0 to 29.9, 30.0 to 34.9, 35.0 to 39.9,
      and> or =40.0 kg/m(2), respectively. Metabolic syndrome was defined according to
      the 2004 National Heart, Lung and Blood Institute/American Heart Association
      conference proceedings. RESULTS: With increasing overweight and obesity class,
      there is an increase in the prevalence of hypertension (18.1% for normal weight
      to 52.3% for obesity class 3), diabetes (2.4% for normal weight to 14.2% for
      obesity class 3), dyslipidemia (8.9% for normal weight to 19.0% for obesity class
      3), and metabolic syndrome (13.6% for normal weight to 39.2% for obesity class
      3). With normal weight individuals as a reference, individuals with obesity class
      3 had an adjusted odds ratio of 4.8 (95% CI 3.8 to 5.9) for hypertension, 5.1
      (95% CI 3.7 to 7.0) for diabetes, 2.2 (95% CI 1.7 to 2.4) for dyslipidemia, and
      2.0 (95% CI 1.4 to 2.8) for metabolic syndrome. CONCLUSIONS: The prevalence of
      hypertension, diabetes, dyslipidemia, and metabolic syndrome substantially
      increases with increasing body mass index. These findings have important public
      health implications for the prevention and treatments (surgical and nonsurgical)
      of obesity.

PMID- 19183542
TI  - Improving perioperative outcomes: fluid optimization with the esophageal Doppler
      monitor, a metaanalysis and review.

PMID- 19183543
TI  - Specific interventions to increase women's interest in surgery.

PMID- 19183544
TI  - Evolution of the surgical glove.

PMID- 19183546
TI  - Acute appendicitis in situs inversus totalis.

PMID- 19183547
TI  - Assessment of lumbar fusion: importance of dynamic plain standing x-rays.

PMID- 19183549
TI  - The use of fine nets to prevent the breeding of mosquitoes on dry farmland in
      southern Taiwan.
AB  - OBJECTIVES: The stagnate water stored in buckets traditionally used by farmers in
      southern Taiwan to irrigate their dry farmland, serves as favorable breeding
      ground for Aedes aegypti, the vector of the dengue virus. The public health
      bureau there distributed fine nets to the farmers to cover their buckets to
      reduce vector breeding sites. The goal of this study was to compare the container
      index (CI) in Alian and Tianliao Townships, Kaohsiung County in southern Taiwan
      over a 2-year period, for 1 year before the fine nets were distributed and 1 year
      after. METHODS: In March 2005, we selected eight villages in Alian Township and
      10 in Tianliao Township. Specialists monitored the local Stegomyia indices every
      month. We compared the 2005 CI to the 2004 CI, representing the years before and
      after the nets were used. The results of the comparisons were analyzed by paired
      t-test and Wilcoxon rank test. RESULTS: In Alian Township, mean CI had
      significantly reduced to 1.63 levels (May 2005) from a mean 5.88 level in May
      2004 (paired t-test, p=0.001 and Wilcoxon rank signed test, p=0.0012). In
      Tianliao Township, CI was reduced to 1.2 from 2.3 in May 2004 (p<0.0001 and
      p=0.007, paired t-test and Wilcoxon rank signed test, respectively). CONCLUSIONS:
      The nets effectively reduced the CIs in these townships, and might be considered
      for wide scale use. The mosquito nets were generally welcomed by the farmers who
      found them to be convenient, inexpensive and practical.

PMID- 19183550
TI  - Evaluation of an IgG-ELISA strategy using Taenia solium metacestode somatic and
      excretory-secretory antigens for diagnosis of neurocysticercosis revealing
      biological stage of the larvae.
AB  - Diagnosis of neurocysticercosis (NCC) is complicated because of the variability
      in clinical presentations and course of the disease where viability of parasite
      is a major determinant. The present study describes evaluation of ELISAs using
      Taenia solium metacestode somatic and excretory-secretory (ES) antigens for
      detection of anti-T. solium metacestode IgG antibodies in serum and cerebrospinal
      fluid (CSF). And results of the ELISAs in cases with a definitive diagnosis of
      NCC are correlated with the biological stages of the parasite such as live
      vesicular or degenerated stage. The sensitivity of the IgG-ELISA using ES antigen
      is observed to be much higher in serum (88.2%) than in CSF (64.28%) although it
      is only marginally higher in serum (76.4%) than in CSF (75%) when somatic antigen
      is used in the ELISA. Whereas, the specificities of the ELISA using either
      somatic or ES antigen for detection of IgG antibodies in serum (97.97%; 96.96%)
      and CSF (96.42%; 97.61%) are comparable. A strong association is observed between
      live stage of the parasite and detection of antibodies in sera and CSF from more
      number of NCC patients by ELISA using ES antigens. Similarly, detection of
      antibodies by ELISA using somatic antigens could be associated with the dead or
      degenerated stage of the parasite in brain. The IgG-ELISA strategy developed in
      the present study opens up an avenue for diagnosis of NCC in hospitals or in
      population prevalence studies. The use of crude extracts of ES proteins might
      improve the serodiagnosis of the cases of NCC carrying live vesicular stage of
      the parasite larvae.

PMID- 19183551
TI  - Inhibition of alpha-synuclein fibril assembly by small molecules: analysis using
      epitope-specific antibodies.
AB  - The conversion of soluble peptides and proteins into amyloid fibrils and/or
      intermediate oligomers is believed to be the central event in the pathogenesis of
      most human neurodegenerative diseases. Existing treatments are at best
      symptomatic. Accordingly, small molecule inhibitors of amyloid fibril formation
      and their mechanisms are of great interest. Here we report that the
      conformational changes undergone by alpha -synuclein as it assembles into amyloid
      fibrils can be detected by epitope-specific antibodies. We show that the
      conformations of polyphenol-bound alpha-synuclein monomers and dimers differ from
      those of unbound monomers and resemble amyloid fibrils. This strongly suggests
      that small molecule inhibitors bind and stabilize intermediates of amyloid fibril
      formation, consistent with the view that inhibitor-bound molecular species are on
      pathway intermediates.

PMID- 19183552
TI  - A single amino acid residue is responsible for species-specific incompatibility
      between CCT and alpha-actin.
AB  - Actin is dependent on the type-II chaperonin CCT (chaperonin containing TCP-1) to
      reach its native state. In vitro, yeast CCT folds yeast and also mammalian
      cytoplasmic (beta/gamma) actins but is now found to be incapable of folding
      mammalian skeletal muscle alpha-actin. Arrest of alpha-actin on yeast CCT at a
      folding cycle intermediate has been observed by electron microscopy. This
      discovery explains previous observations in vivo that yeast mutants expressing
      only the muscle actin gene are non-viable. Mutational analysis identified a
      single specific alpha-actin residue, Asn-297, that confers this species/isoform
      folding specificity. The implications of this incompatibility for chaperonin
      mechanism and actin-CCT co-evolution are discussed.

PMID- 19183553
TI  - Degradation of transglutaminase 2 by calcium-mediated ubiquitination responding
      to high oxidative stress.
AB  - Transglutaminase 2 (TG2) is a calcium-dependent enzyme that catalyzes the
      transamidation reaction. There is conflicting evidence on the role of TG2 in
      apoptosis. In this report, we show that TG2 increases in response to low level of
      oxidative stress, whereas TG2 diminishes under high stress conditions. Monitoring
      TG2 expression, activity and calcium concentration in cells treated with A23187
      revealed that the initial rise of calcium activates TG2 but subsequent calcium
      overload induces the degradation of TG2 via calcium-mediated polyubiquitination.
      These results indicate that the role of TG2 in apoptosis depends on the level of
      calcium influx triggered by oxidative stress.

PMID- 19183554
TI  - A single mutation in an SH3 domain increases amyloid aggregation by accelerating
      nucleation, but not by destabilizing thermodynamically the native state.
AB  - We investigated the relationship between thermodynamic stability and amyloid
      aggregation propensity for a set of single mutants of the alpha-spectrin SH3
      domain (Spc-SH3). Whilst mutations destabilizing the domain at position 56 did
      not enhance fibrillation, the N47A mutation increased the rate of amyloid fibril
      formation by 10-fold. Even under conditions of identical thermodynamic stability,
      the aggregation rate was much higher for the N47A mutant than for the WT domain.
      We conclude that the N47A mutation does not change the apparent mechanism of
      fibrillation or the morphology of the amyloid fibrils, and that its amyloidogenic
      property is due to its effect upon the rate of the conformational events leading
      to nucleation and not to its overall destabilizing effect.

PMID- 19183555
TI  - Efficient purification of eosinophils from human tissues: a comparative study.
AB  - BACKGROUND: Eosinophils are key effector cells in allergy and in other
      inflammatory diseases. Although they carry out their function in the tissues, no
      efficient method exists allowing for consistent purification of tissue
      eosinophils for culture. Rather, studies rely mainly on peripheral blood
      eosinophils. This study aimed to determine the most efficient protocol for
      purifying eosinophils from nasal polyp tissue. METHODS: Nasal polyps were
      obtained from patients undergoing surgical polypectomy. The polyps were minced
      and enzymatically digested. Surface receptor analysis was performed by flow
      cytometry. In order to obtain optimal purification, the nasal polyp cell
      suspension was subjected to two methods of purification: 1) positive magnetic
      selection of CCR3+cells, or 2) negative selection using CD3/CD14/CD16 magnetic
      beads. Enriched tissue eosinophils were cultured with or without IL-3, IL-5 or GM
      CSF, and their survival was evaluated by flow cytometry. RESULTS: Tissue-derived
      eosinophils exhibited surface expression of NEC2, DNAM-1, NTBa, 2B4, and CD300a
      comparable to similarly prepared eosinophils obtained from the peripheral blood
      of the same patients. Positive selection consistently yielded eosinophils of high
      purity (>90%) with 63% viability. In contrast, negative selection yielded better
      viability (88%), reduced purity (66%), and could be utilized for in vitro
      activation experiments. CONCLUSION: Eosinophils can be purified from nasal
      polyps. Negative selection appears to be advantageous due to improved viability
      of the eosinophils, which may be cultured and activated in vitro. This
      methodology is an important advance in studying tissue eosinophils for further
      investigations on inflammatory tissue responses.

PMID- 19183556
TI  - Heme-binding storage proteins in the Chelicerata.
AB  - Lipoglycoproteins in the Chelicerata that bind and store heme appear to represent
      a unique evolutionary strategy to both mitigate the toxicity of heme and utilize
      the molecule as a prosthetic group. Knowledge of heme-binding storage proteins in
      these organisms is in its infancy and much of what is known is from studies with
      vitellogenins (Vg) and more recently the main hemolymph storage protein in ixodid
      ticks characterized as a hemelipoglyco-carrier protein (CP). Data have also been
      reported from another arachnid, the black widow spider, Latrodectus mirabilis,
      and seem to suggest that the heme-binding capability of these large multimeric
      proteins is not a phenomenon found only in the Acari. CP appears to be most
      closely related to Vg in ticks in terms of primary structure but post
      translational processing is different. Tick CP and L. mirabilis high-density
      lipoprotein 1 (HDL1) are similar in that they consist of two subunits of
      approximate molecular masses of 90 and 100 kDa, are found in the hemolymph as the
      dominant protein, and bind lipids, carbohydrates and cholesterol. CP binds heme
      which may also be the case for HDL1 since the protein was found to contain a
      brown pigment when analyzed by native polyacrylamide gel electrophoresis. Vgs in
      ticks are composed of multiple subunits and are the precursor of the yolk
      protein, vitellin. The phylogeny of these proteins, regulation of gene expression
      and putative functions of binding and storing heme throughout reproduction, blood
      feeding and development are discussed. Comparisons with non-chelicerate
      arthropods are made in order to highlight the mechanisms and putative functions
      of heme-binding storage proteins and their possible critical function in the
      evolution of hematophagy.

PMID- 19183557
TI  - Age- and morph-dependent activation of the lysosomal system and Buchnera
      degradation in aphid endosymbiosis.
AB  - Endosymbiosis in aphids is maintained through a mutualistic association between
      the host and a symbiotic bacterium, Buchnera, which is harbored in specialized
      host cells called bacteriocytes. Here, we examined the changes in the Buchnera
      density in bacteriocytes in relation to the development and polyphenism of the
      host aphid. Buchnera density in the winged morph aphids, alatae, decreased
      drastically around the final ecdysis, whereas in the wingless morph aphids,
      apterae, Buchnera density decreased after the final ecdysis. Thereafter, in both
      apterae and alatae, Buchnera density was maintained at a constant level until 10
      days and then again decreased gradually until 18 days after the final ecdysis.
      Cytochemical analysis with LysoTracker reagent and quantitative RT-PCR analysis
      revealed that the number of lysosome-like acidic organelles and the amount of
      lysosome-related gene (lysozyme and cathepsin L) transcripts increased
      drastically in the bacteriocytes of alatae around the final ecdysis. Electron
      microscopy of alatae bacteriocytes around the final ecdysis revealed many
      Buchnera with irregular electron-dense areas in their cytoplasm that were
      enclosed by a distended symbiosome membrane. These findings indicated that age-
      and morph-dependent decreases in Buchnera density coincided with activation of
      the host lysosomal system and the increased degradation of Buchnera.

PMID- 19183558
TI  - Diapause induction and clock mechanism in the cabbage butterfly Pieris melete
      Menetries.
AB  - Photoperiodic control of diapause induction was systematically investigated in
      the cabbage butterfly, Pieris melete, which enters summer and winter diapause as
      a pupa. Summer and winter diapause are induced principally by short and long
      scotophases, respectively; the intermediate scotophases (11-12 h) permit pupae to
      develop without diapause. Photoperiodic responses under 24-h light-dark cycles at
      16.9, 18, 20 and 22 degrees C showed that the hibernation response was
      temperature compensated, whereas aestivation response was strongly temperature
      dependent. The incidence of diapause for both aestivation and hibernation showed
      a decline at the ultra-short and ultra-long scotophases. Experiments using non-24
      h light-dark cycles showed that the length of the scotophase played an essential
      role in the determination of diapause. The highest photosensitivity differed
      under hibernation and aestivation conditions. With a 3 x LD 12:12 interruption, a
      maximal inhibition of aestivation occurred in the L3/2 stage, and of hibernation
      it occurred in the L4/0 stage. A long-night of LD 10:14 induced hibernation
      diapause but inhibited aestivation diapause and, conversely, a short-night of LD
      14:10 inhibited hibernation diapause but induced aestivation diapause. With a 1-h
      light pulse at LD 11:13, a maximal inhibition of hibernation occurred 3 h before
      lights-on (late scotophase), whereas, with a 1-h light pulse at LD 12.5:11.5, a
      maximal induction of aestivation occurred 2-3 h after the onset of darkness
      (early scotophase). Nanda-Hamner and Bunsow experiments failed to reveal the
      involvement of a circadian system, suggesting that the photoperiodic time
      measurement for diapause induction in this butterfly resembles an hourglass-like
      timer or a damped circadian oscillator.

PMID- 19183559
TI  - Prediction of protein structural classes by recurrence quantification analysis
      based on chaos game representation.
AB  - In this paper, we intend to predict protein structural classes (alpha, beta,
      alpha+beta, or alpha/beta) for low-homology data sets. Two data sets were used
      widely, 1189 (containing 1092 proteins) and 25PDB (containing 1673 proteins) with
      sequence homology being 40% and 25%, respectively. We propose to decompose the
      chaos game representation of proteins into two kinds of time series. Then, a
      novel and powerful nonlinear analysis technique, recurrence quantification
      analysis (RQA), is applied to analyze these time series. For a given protein
      sequence, a total of 16 characteristic parameters can be calculated with RQA,
      which are treated as feature representation of protein sequences. Based on such
      feature representation, the structural class for each protein is predicted with
      Fisher's linear discriminant algorithm. The jackknife test is used to test and
      compare our method with other existing methods. The overall accuracies with step
      by-step procedure are 65.8% and 64.2% for 1189 and 25PDB data sets, respectively.
      With one-against-others procedure used widely, we compare our method with five
      other existing methods. Especially, the overall accuracies of our method are 6.3%
      and 4.1% higher for the two data sets, respectively. Furthermore, only 16
      parameters are used in our method, which is less than that used by other methods.
      This suggests that the current method may play a complementary role to the
      existing methods and is promising to perform the prediction of protein structural
      classes.

PMID- 19183560
TI  - A mathematical model of doxorubicin penetration through multicellular layers.
AB  - Inadequate drug delivery to tumours is now recognised as a key factor that limits
      the efficacy of anticancer drugs. Extravasation and penetration of therapeutic
      agents through avascular tissue are critically important processes if sufficient
      drug is to be delivered to be therapeutic. The purpose of this study is to
      develop an in silico model that will simulate the transport of the clinically
      used cytotoxic drug doxorubicin across multicell layers (MCLs) in vitro. Three
      cell lines were employed: DLD1 (human colon carcinoma), MCF7 (human breast
      carcinoma) and NCI/ADR-Res (doxorubicin resistant and P-glycoprotein [Pgp]
      overexpressing ovarian cell line). Cells were cultured on transwell culture
      inserts to various thicknesses and doxorubicin at various concentrations (100 or
      50 microM) was added to the top chamber. The concentration of drug appearing in
      the bottom chamber was determined as a function of time by HPLC-MS/MS. The rate
      of drug penetration was inversely proportional to the thickness of the MCL. The
      rate and extent of doxorubicin penetration was no different in the presence of
      NCI/ADR-Res cells expressing Pgp compared to MCF7 cells. A mathematical model
      based upon the premise that the transport of doxorubicin across cell membrane
      bilayers occurs by a passive "flip-flop" mechanism of the drug between two
      membrane leaflets was constructed. The mathematical model treats the transwell
      apparatus as a series of compartments and the MCL is treated as a series of cell
      layers, separated by small intercellular spaces. This model demonstrates good
      agreement between predicted and actual drug penetration in vitro and may be
      applied to the prediction of drug transport in vivo, potentially becoming a
      useful tool in the study of optimal chemotherapy regimes.

PMID- 19183561
TI  - The saccadic Stroop effect: Evidence for involuntary programming of eye movements
      by linguistic cues.
AB  - The effect of automatic priming of behaviour by linguistic cues is well
      established. However, as yet these effects have not been directly demonstrated
      for eye movement responses. We investigated the effect of linguistic cues on eye
      movements using a modified version of the Stroop task in which a saccade was made
      to the location of a peripheral colour patch which matched the "ink" colour of a
      centrally presented word cue. The words were either colour words ("red", "green",
      "blue", "yellow") or location words ("up", "down", "left", "right"). As in the
      original version of the Stroop task the identity of the word could be either
      congruent or incongruent with the response location. The results showed that
      oculomotor programming was influenced by word identity, even though the written
      word provided no task relevant information. Saccade latency was increased on
      incongruent trials and an increased frequency of error saccades was observed in
      the direction congruent with the word identity. The results argue against
      traditional distinctions between reflexive and voluntary programming of saccades
      and suggest that linguistic cues can also influence eye movement programming in
      an automatic manner.

PMID- 19183562
TI  - Involvement of protein kinase C signalling and mitogen-activated protein kinase
      in the amebocyte-producing organ of Biomphalaria glabrata (Mollusca).
AB  - Mechanisms that regulate hemocyte production in molluscs, at either the
      organismal or cellular levels, are not well understood. In the present study, 24
      h saline cultures of the amebocyte-producing organ (APO) of the schistosome
      transmitting snail Biomphalaria glabrata were used to test for the potential
      involvement of protein kinase C (PKC) signalling in hematopoiesis. Exposure to
      phorbol myristate acetate (PMA), an activator of PKC, resulted in an increase in
      the number of dividing hematopoietic cells in APOs from schistosome-resistant
      Salvador snails. PMA-induced cell division was blocked by treatment with U0126,
      an inhibitor of the mitogen-activated protein kinase kinase, MEK1/2. These
      results suggest that PKC-induced activation of the mitogen-activated protein
      kinase, ERK1/2, is involved in cell division in the APO.

PMID- 19183563
TI  - Quantifying repeatability of the Wartenberg pendulum test parameters in children
      with spasticity.
AB  - The Wartenberg (pendulum) test is commonly used in a variety of studies involving
      healthy subjects, patients with CP, stroke patients, and other neurological
      conditions. There is some evidence that the Wartenberg test may be able to
      differentiate healthy people from patients with spasticity. The aim of the study
      was to explore the within-session repeatability of primary outcome measures, i.e.
      relaxation indices derived from the Wartenberg test when test was performed by
      single investigator. Patients were lying supine, thigh along the horizontal line.
      The lower legs were allowed to hang freely over the table edge, and the knee
      motion in response to leg drop from the horizontal position was measured using
      motion system VICON with external markers attached to each leg at greater
      trochanter, lateral knee epicondyle, and lateral malleolus. Data from four
      consecutive trials were collected at 1 min intervals. The set of relaxation
      indices and maximum velocity was calculated for each trial. Data of 21 children
      (42 limbs) who underwent the evaluation due to spasticity problem were analysed.
      The repeated measure ANOVA test, one way analysis of variance, coefficients of
      correlation and determination were used to determine the repeatability of the
      relaxation indices, the association between the indices in time, and influence of
      the spasticity origin on the variability. The results show that relaxation
      indices, did not differ between the trails in statistically significant way in
      our group of patients with spasticity, however they exhibited high within-session
      variability in the individual patients (16-90%). Therefore the variability of the
      relaxation indices may restrict the clinical usefulness of the indices to monitor
      the changes of spasticity over time. Further, our findings do not seem to conform
      to the earlier reports demonstrating a systematic, time-dependent, change in the
      relaxation indices when repeated measures were taken within a session. In
      conclusion, this study demonstrates that although the Wartenberg test is
      repeatable in groups of patients, it does not provide us with repeatable measures
      in individual patients, thus if it is to be used as a replacement for other
      clinical tests of spasticity further investigations are needed to explain the
      substantial variability of the indices.

PMID- 19183564
TI  - The drug monosodium luminol (GVT) preserves thymic epithelial cell
      cytoarchitecture and allows thymocyte survival in mice infected with the T cell
      tropic, cytopathic retrovirus ts1.
AB  - A mutant of MoMuLV, called ts1, causes an AIDS-like syndrome in susceptible
      strains of mice. In mice infected at birth, thymic atrophy, CD4+ T cell loss,
      body wasting, and death occur by approximately 30-40 days postinfection (dpi). We
      have shown previously that the death of ts1-infected cells is not caused by viral
      replication per se, but by oxidative stress and apoptosis following their
      accumulation the ts1 viral envelope precursor protein, gPr80(env). In infected
      mice treated with the antioxidant monosodium alpha-luminol (GVT), T cell loss and
      thymic atrophy are delayed for many weeks, and body wasting and death do not
      occur until long after infected, untreated control mice have died. We show here
      that GVT treatment of ts1-infected mice maintains the thymic epithelial cell
      (TEC) cytoarchitecture and cytokeratin gradients required for thymocyte
      differentiation. It also suppresses thymocyte reactive oxygen species (ROS)
      levels, upregulates and stabilizes levels of the antioxidant-regulating
      transcription factor Nrf2, and prevents accumulation of gPr80(env) in thymocytes.
      We conclude that GVT treatment can make ts1 a non-cytopathic virus for
      thymocytes, although it cannot prevent thymocyte infection. Since oxidative
      stress also contributes to the loss of T cells in HIV-AIDS, the antioxidant
      effects of GVT may make it a useful therapeutic adjunct to HAART treatment.

PMID- 19183566
TI  - Laser system range calculations and the Lambert W function.
AB  - The knowledge of range performance versus atmospheric transmission, often given
      by the visibility, is critical for the design, use, and prediction of laser and
      passive electro-optic systems. I present a solution of the ladar-lidar equation
      based on Lambert's W function. This solution will reveal the dependence of the
      maximum range on the system and target parameters for different atmospheric
      attenuations and will also allow us to take the signal statistics into account by
      studying the influence on the threshold signal-to-noise ratio. The method is also
      applicable to many range calculations for passive systems where the atmospheric
      loss can be approximated by an exponential term.

PMID- 19183565
TI  - Adaptor molecules expression in normal lymphopoiesis and in childhood leukemia.
AB  - Transmembrane adaptor proteins are key mediators of antigen receptor signaling in
      lymphocytes. By influencing proliferation and differentiation, these molecules
      might play a role in ethiopathogenesis of acute lymphoblastic leukemia (ALL). The
      aim of this study was to characterize expression of PAG, LAT, NTAL and LIME
      adaptors at the mRNA and protein levels in normal B- and T-precursors. Moreover,
      diagnostic samples of childhood ALL cases were analyzed. During normal lymphocyte
      development, some adaptors show significant dynamics (gradual decrease of NTAL
      and increase of LAT and LIME during the T-cell maturation, decrease of PAG in B
      precursors, high levels of LIME in peripheral B-lymphocytes). Analysis of
      childhood ALL samples revealed that in B-cell precursor ALL, the TEL/AML1
      subgroup have unique adaptor profile compared to other leukemias. Moreover, NTAL
      expression separates T lineage leukemias into two subgroups with good and poor
      response to initial prednisone therapy showing prognostic impact of this molecule
      in T-ALL.

PMID- 19183567
TI  - Optical emission enhancement of laser-produced copper plasma under a steady
      magnetic field.
AB  - From a copper target, laser-ablated plasma was investigated by spectral- and
      temporal-resolved emission spectroscopy. With the presence of a 0.8 T steady
      magnetic field, the emission of the expanding plasma showed significant
      enhancements of the spectral lines for all neutral, singly, and doubly ionized
      species. The relative enhancements for different species have been studied with
      temporal-resolved measurement by comparing the spectra obtained with and without
      the magnetic field. The enhanced emission from the plasma plume is attributed to
      an increase of the radiative recombination rate in the plasma due to magnetic
      confinement. The temporal evolution of the plasma parameters, including electron
      temperature and electron density, was deduced and discussed for the cases with
      and without a magnetic field.

PMID- 19183568
TI  - Fluorescence lifetime and intensity of terbium-doped dipicolinic acid in water,
      HCl, and sodium acetate buffer solutions.
AB  - The lifetimes of the individual fluorescing lines from the terbium-doped
      dipicolinic acid (DPA) complex have been measured and reported, for the first
      time to our knowledge. These lifetimes have been measured as a function of
      terbium and dipicolinic acid concentration, solvent pH, and solvent composition
      for water, HCl, and sodium acetate buffer solutions. Fluorescence lifetimes over
      the range from 0.75 to 1.07 ms were measured. The maximum fluorescence was
      obtained for distilled water solutions.

PMID- 19183569
TI  - Resonant tuning fork detector for electromagnetic radiation.
AB  - A mechanical quartz microresonator (tuning fork) is used to detect
      electromagnetic radiation. The detection scheme is based on forces created due to
      the incident electromagnetic radiation on the piezoelectric tuning fork. A force
      can be created due to the transfer of the photon momentum of the incident
      electromagnetic radiation. If the surfaces of the tuning fork are nonuniformly
      heated, a second force acts on it, the so-called photophoretic force. These
      processes occur for all wavelengths of the incident radiation, making the
      detector suitable for sensing of ultraviolet, visible, and mid-infrared light,
      even THz-radiation. Here the detector is characterized in the visible range;
      noise analysis is performed for 650 nm and 5.26 microm. A linear power
      characteristic and the dependence on pulse lengths of the incoming light are
      shown. Examples for applications for the visible and mid-infrared spectral region
      are given by 2f and absorption spectroscopy of oxygen and nitric oxide,
      respectively.

PMID- 19183570
TI  - Classification and selective collection of individual aerosol particles using
      laser-induced fluorescence.
AB  - We describe the development and performance evaluation of a system for optical
      interrogation, subsequent selection, and collection of individual aerosol
      particles entrained in an inlet air stream. Elastic scatter and laser-induced
      fluorescence obtained from single particles on-the-fly provide compositional
      information for classification criteria. Individual particles could then be
      selectively electrically charged and captured to a conductive substrate with an
      electric potential. The optical subsystem also includes a novel two-beam
      velocimeter to provide accurate downstream timing. Good overall quantitative
      performance values are reported for particles in the size range of 1-8 microm at
      mean rates up to 4 kHz.

PMID- 19183571
TI  - Ultrafast time-gated ballistic-photon imaging and shadowgraphy in optically dense
      rocket sprays.
AB  - Time-gated ballistic-photon imaging is a form of shadowgraphy in which an
      ultrashort, optical-Kerr-effect (order 2 ps) time gate is used to enhance the
      relative intensity of ballistic versus multiply scattered photons. In the current
      work, this technique is adapted for what is believed to be the first time for use
      in the moderately dense environment (optical density approximately 1.5 to 2) of a
      high-speed 5 to 15 mm diameter rocket spray to improve image contrast and observe
      liquid-breakup phenomena. Unlike coherence gating, which is another form of
      ballistic imaging, the time-gating approach allows sufficient signal levels from
      ballistic and near-ballistic photons to enable time-resolved single-shot imaging.
      Direct comparisons with non-time-gated shadowgraphy indicate that the two
      techniques are sensitive to different features of the flowfield, with regions
      composed of a dense field of droplets being highly attenuated in conventional
      shadowgrams but appearing transparent to ballistic photons. This enables
      significant image contrast enhancement (approximately 6.6:1) of liquid-core
      structures and facilitates improved understanding of the primary and secondary
      breakup processes in sprays of moderate optical density.

PMID- 19183572
TI  - Differential absorption lidar CO2 laser system for remote sensing of TATP related
      gases.
AB  - A CW tunable 10.6 microm CO(2) laser differential absorption lidar (DIAL) system
      has been developed, for the first time to our knowledge, for the remote sensing
      of triacetone triperoxide (TATP) gas vapors, which have strong absorption lines
      at several wavelengths, including 3.3, 8.3, and 10.6 microm. The DIAL laser beam
      was transmitted through an enclosed absorption cell containing TATP or SF(6), and
      backscattered returns were measured from a retroreflector array target at ranges
      of 5-100 m. DIAL sensitivity for the detection of TATP was about 0.5 ng/microl
      [52 parts in 10(6)(ppm)] for a 0.3 m path.

PMID- 19183573
TI  - Optical waveguide light-mode spectroscopy immunosensors for environmental
      monitoring.
AB  - Coupling the high specificity of the immunoanalytical reaction with the high
      sensitivity of optical waveguide light-mode spectroscopy (OWLS) detection gives
      the possibility to develop immunosensors with in most cases a definitely lower
      detection limit than traditionally used immunoassays. Measurements were performed
      on the sensitized surface of optical waveguide grating coupler sensors (2400
      lines/mm grating). The OWLS technique is based on the precise measurement of the
      resonance angle of a polarized laser light (632.8 nm), diffracted by a grating
      and incoupled into a thin waveguide. The effective refractive index, determined
      from the resonance incoupling angle detected at high accuracy, allows
      determination of layer thickness and coverage (or mass) of the adsorbed or bound
      material with ultrahigh sensitivity. OWLS immunosensors were developed as label
      free immunosensors with an amino group modified SiO(2)-TiO(2) sensor surface on
      which the immunoreactants could be anchored. One of the components of the
      antibody-antigen complex was chemically bound on the sensor surface, allowing
      noncompetitive or competitive detection of the analytes. To illustrate that the
      resulting immunosensors are suitable for the determination of small and large
      molecular weight analytes, OWLS sensor formats were applied for quantitative
      detection of a herbicide active ingredient trifluralin, a Fusarium mycotoxin
      zearalenone, and an egg yolk protein of key importance in endocrine regulation,
      vitellogenin.

PMID- 19183574
TI  - Long optical cavities for open-path monitoring of atmospheric trace gases and
      aerosol extinction.
AB  - An incoherent broadband cavity-enhanced absorption spectroscopy setup employing a
      20 m long optical cavity is described for sensitive in situ measurements of light
      extinction between 630 and 690 nm. The setup was installed at the SAPHIR
      atmospheric simulation chamber during an intercomparison of instruments for
      nitrate (NO(3)) radical detection. The long cavity was stable for the entire
      duration of the two week campaign. A detection limit of approximately 2 pptv for
      NO(3) in an acquisition time of 5 s was established during that time. In addition
      to monitoring NO(3), nitrogen dioxide (NO(2)) concentrations were simultaneously
      retrieved and compared against concurrent measurements by a chemiluminescence
      detector. Some results from the campaign are presented to demonstrate the
      performance of the instrument in an atmosphere containing water vapor and
      inorganic aerosol. The spectral analysis of NO(3) and NO(2), the concentration
      dependence of the water absorption cross sections, and the retrieval of aerosol
      extinction are discussed. The first deployment of the setup in the field is also
      briefly described.

PMID- 19183575
TI  - Standoff and arms-length detection of chemicals with single-beam coherent anti
      Stokes Raman scattering.
AB  - The detection of chemicals from safe distances is vital in environments with
      potentially hazardous or explosive threats, where high sensitivity and fast
      detection speed are needed. Here we demonstrate standoff detection of several
      solids, liquids, and gases with single-beam coherent anti-Stokes Raman
      scattering. This approach utilizes a phase coherent ultrabroad-bandwidth
      femtosecond laser to probe the fundamental vibrations that constitute a
      molecule's fingerprint. Characteristic Raman lines for several chemicals are
      successfully obtained from arms-length and 12 m standoff distances. The
      sensitivity and speed of this approach are also demonstrated.

PMID- 19183576
TI  - Distributed feedback diode laser spectrometer at 2.7 microm for sensitive,
      spatially resolved H2O vapor detection.
AB  - A new, compact, spatially scanning, open-path 2.7 microm tunable diode laser
      absorption spectrometer with short absorption path lengths below 10 cm was
      developed to analyze the spatiotemporal dynamics of one-dimensional (1D) spatial
      water vapor gradients. This spectrometer, which is based on a room-temperature
      distributed feedback diode laser, is capable of measuring absolute, calibration
      free, line-of-sight averaged, but laterally resolved 1D H(2)O concentration
      profiles with a minimum fractional optical resolution of 2.1x10(-3) optical
      density (OD) (2.5x10(-4) OD after a background subtraction procedure), which
      permits a signal-to-noise-ratio of 407 (3400) at 10,000 parts in 10(6)
      (ppm)H(2)O, or normalized sensitivities of 2.6 ppm x m (0.32 ppm m) at 0.5 Hz
      duty cycle. The spectrometer's lateral spatial resolution (governed by the 500
      microm sampling beam diameter) was validated by analyzing a well-defined laminar
      jet of nitrogen gas in humidified air. This scanning setup was then used to (a)
      quantitatively investigate for what we believe to be the first time the H(2)O
      boundary layer from 0.7 to 11 mm beneath the stomatous side of a single,
      undetached plant leaf, and (b) to study the temporal boundary layer dynamics and
      its dependence on stepwise light stimulation of the photosynthetic system. In
      addition the 2.7 microm diode laser was carefully characterized in terms of
      spectral purity, beam profile, as well as quasi-static and dynamic wavelength
      tuning coefficients.

PMID- 19183577
TI  - Evanescent field sensors and the implementation of waveguiding nanostructures.
AB  - Conventional fiber optic evanescent-field gas sensors are based on a high number
      of total reflections while the gas is passing the active bare core fiber and of
      course a suitable laser light source. The use of miniaturized laser sources for
      sensitive detection of CO(2) in gaseous and water-dissolved phase for
      environmental monitoring are studied for signal enhancing purposes. Additionally,
      the fiber optic sensor, consisting of a coiled bare multimode fiber core, was
      sensitized by an active polymer coating for the detection of explosive TNT. The
      implementation of ZnO waveguiding nanowires is discussed for surface and
      sensitivity enhancing coating of waveguiding elements, considering computational
      and experimental results.

PMID- 19183578
TI  - Advances in generation of high-repetition-rate burst mode laser output.
AB  - It is demonstrated that the incorporation of variable pulse duration flashlamp
      power supplies into an Nd:YAG burst mode laser system results in very substantial
      increases in the realizable energy per pulse, the total pulse train length, and
      uniformity of the intensity envelope. As an example, trains of 20 pulses at burst
      frequencies of 50 and 20 kHz are demonstrated with individual pulse energy at
      1064 nm of 220 and 400 mJ, respectively. Conversion efficiency to the second-
      (532 nm) and third- (355 nm) harmonic wavelengths of approximately 50% and 35
      40%, respectively, is also achieved. Use of the third-harmonic output of the
      burst mode laser as a pump source for a simple, home built optical parametric
      oscillator (OPO) produces pulse trains of broadly wavelength tunable output. Sum
      frequency mixing of OPO signal output at 622 nm with residual output from the 355
      nm pump beam is shown to produce uniform bursts of tunable output at
      approximately 226 nm, with individual pulse energy of approximately 0.5 mJ. Time
      correlated NO planar laser induced fluorescence (PLIF) image sequences are
      obtained in a Mach 3 wind tunnel at 500 kHz, representing, to our knowledge, the
      first demonstration of NO PLIF imaging at repetition rates exceeding tens of
      hertz.

PMID- 19183579
TI  - Impact of collisional quenching on the detection of HgCl2 via photofragment
      emission.
AB  - The effects of collisional quenching on photofragment emission (PFE) detection of
      vapor-phase HgCl(2) in combustion flue gas constituents are investigated.
      Exciting HgCl(2) via the 1(1)Pi(u)<--1(1)Sigma(g)+ transition, time-resolved
      measurements of emission from the Hg(6(3)P(1)) daughter in buffer-gas mixtures of
      N(2), O(2), and CO(2) indicate that the fragmentation pathway passes through a
      long-lived intermediate species, which we assign to Hg(6(3)P(2)). Total quenching
      rate coefficients of Hg(6(3)P(1)) by N(2), O(2), and CO(2) are consistent with
      values reported in the literature. In addition, total quenching rate coefficients
      for the intermediate Hg(6(3)P(2)) state are determined to be 1.72(+/-0.08)x10(
      10) cm(3) molecule(-1) s(-1) and 2.90(+/-0.37)x10(-10) cm(3) molecule(-1) s(-1)
      for N(2) and O(2), respectively. An analysis of the impact of the collisionally
      dependent energy-transfer process that precedes the formation of Hg(6(3)P(1)) on
      the use of PFE to measure HgCl(2) concentration is presented.

PMID- 19183580
TI  - Development of a simplified dual-pump dual-broadband coherent anti-Stokes Raman
      scattering system.
AB  - A dual-pump dual-broadband coherent anti-Stokes Raman scattering (CARS) setup for
      simultaneous pure rotational and vibrational CARS is further developed by
      reducing the experimental efforts due to the use of only one detection system.
      With this system dual-pump CARS for probing ro-vibrational transitions of
      N(2)/CO/H(2) and dual-broadband CARS for pure rotational transitions of
      N(2)/O(2)/CO/CO(2) are applicable simultaneously. In this work the improvements
      to the setup and the data evaluation are described. First simultaneous
      temperature and concentration results from cell measurements and from a partially
      premixed propane flame are presented. Interference effects due to smeared
      vibrational CARS are investigated. It is shown that with similar experimental
      effort to a conventional dual-pump CARS setup considerably more information can
      be gained.

PMID- 19183581
TI  - Widely tunable laterally coupled distributed feedback laser diodes for
      multispecies gas analysis based on InAs/InGaAs quantum-dash material.
AB  - Applying the concept of binary superimposed gratings, widely tunable single-mode
      laser diodes suitable for multispecies gas detection in the 1.8 microm wavelength
      range could be manufactured on InAs/InGaAs quantum dash-in-a-well material. A
      discrete wavelength tuning range of 21 nm as well as continuous tuning over 0.8
      nm are demonstrated. Water and hydrogen chloride could be detected at absorption
      lines 13 nm apart.

PMID- 19183582
TI  - Two-dimensional Raman mole-fraction and temperature measurements for hydrogen
      nitrogen mixture analysis.
AB  - A two-dimensional laser Raman technique was developed and applied to directly
      probe the population number of selected rotational and vibrational energy levels
      of hydrogen and nitrogen. Using three cameras simultaneously, temperature and
      mole fraction images could be detected. Three different combinations of
      rotational and vibrational Raman signals of hydrogen and nitrogen were analyzed
      to identify the combination that is most suitable for future mixture analysis in
      hydrogen internal combustion engines. Here the experiments were conducted in an
      injection chamber where hot hydrogen was injected into room temperature nitrogen
      at 1.1 MPa.

PMID- 19183583
TI  - Development of a picosecond lidar system for large-scale combustion diagnostics.
AB  - In the present work, a picosecond lidar system aiming at single-ended combustion
      diagnostics in full-scale combustion devices with limited optical access, such as
      power plants, is described. The highest overall range resolution of the system
      was found to be <0.5 cm. A demonstration has been made in a nonsooty and sooty
      Bunsen burner flame. A well-characterized ethylene flame on a McKenna burner was
      evaluated for different equivalence ratios using Rayleigh thermometry. The
      results indicate both that picosecond lidar might be applicable for single-shot
      Rayleigh thermometry, even two-dimensional, and that there is a possibility to
      qualitatively map soot occurrence. Furthermore, differential absorption lidar has
      been investigated in acetone vapor jets for fuel visualization purposes.

PMID- 19183584
TI  - Off-axis integrated cavity output spectroscopy with a mid-infrared interband
      cascade laser for real-time breath ethane measurements.
AB  - Cavity-enhanced tunable diode laser absorption spectroscopy is an attractive
      method for measuring small concentrations of gaseous species. Ethane is a breath
      biomarker of lipid peroxidation initiated by reactive oxygen species. A
      noninvasive means of quickly quantifying oxidative stress status has the
      potential for broad clinical application. We present a simple, compact system
      using off-axis integrated cavity output spectroscopy with an interband cascade
      laser and demonstrate its use in real-time measurements of breath ethane. We
      demonstrate a detection sensitivity of 0.48 ppb/Hz(1/2).

PMID- 19183585
TI  - Particle size distribution retrieval from multiwavelength lidar signals for
      droplet aerosol.
AB  - A method of retrieval of the aerosol particle size distribution (APSD) from
      multiwavelength lidar signals is presented. Assumed distribution (usually a
      bimodal combination of lognormal functions) with a few free parameters is
      directly substituted into the lidar equations. The minimization technique allows
      one to find the parameters that provide the best fit of the assumed APSD by
      comparison of theoretically generated and experimental signals. Prior knowledge
      of the lidar ratio is not required. The approach was tested on a typical
      synthetic APSD consisting of spherical droplets. Comparison of lidar measurements
      with results from a condensation particle counter was also performed. For signals
      registered at 3-5 wavelengths from the UV to the near IR a satisfactory retrieval
      of synthetic APSD is possible for the particles within the 100-3000 nm range.

PMID- 19183586
TI  - Quantum cascade laser linewidth investigations for high resolution photoacoustic
      spectroscopy.
AB  - High detection selectivity is extremely important for gas analyzers in order to
      correctly identify the measured compound. Therefore, laser-based systems require
      a high optical resolution, which primarily depends on the spectral linewidth of
      the radiation source. This study examines the effective linewidth (chirp) of a
      pulsed distributed feedback (DFB) quantum cascade laser (QCL) in a photoacoustic
      (PA) gas detection system. The influence of the QCL operating parameters pulse
      duration and pulse current as well as the impact of the modulation technique are
      investigated. Effective QCL linewidths for pulse gate modulation, pulse frequency
      modulation, and chopper modulation are compared. The investigations are performed
      by measuring the PA spectra of nitrogen monoxide absorption lines. The results
      prove the strong influence of pulse duration and pulse current. They also
      demonstrate that the modulation technique has a considerable influence and,
      consequently, affects the detection selectivity of the PA analyzer. The aim of
      this research is to determine optimum operational parameters for high resolution
      PA spectroscopy.

PMID- 19183587
TI  - Assessment of variations in moisture content of wood using time-resolved diffuse
      optical spectroscopy.
AB  - Time-resolved spectroscopy using a pulsed supercontinuum source was employed for
      the assessment of moisture content (MC) in dry wood. The MC of wood at different
      relative humidities between 94% and 12% has been monitored. Following curve
      fitting, absorption spectra between 700 and 1100 nm of samples suggest that
      differences in the MC of wood are appreciable at around 970 nm. Further, dynamic
      changes in MC were simulated following a change in relative humidity. Differences
      in absorption spectra with changes in MC of around 1% can be detected. Various
      applications of the technique are suggested.

PMID- 19183588
TI  - High-speed laser-induced fluorescence and spark plug absorption sensor
      diagnostics for mixing and combustion studies in engines.
AB  - Simultaneous high-speed in-cylinder measurements of laser-induced fluorescence of
      biacetyl as a fuel tracer and mid-infrared broadband absorption of fuel and
      combustion products (water and carbon dioxide) using a spark plug probe are
      compared in an optical engine. The study addresses uncertainties and the
      applicability of absorption measurements at a location slightly offset to the
      spark plug when information about mixing at the spark plug is desired. Absorbance
      profiles reflect important engine operation events, such as valve opening and
      closing, mixing, combustion, and outgassing from crevices.

PMID- 19183590
TI  - Noise analysis in photonic true time delay systems based on broadband optical
      source and dispersion components.
AB  - The noise in photonic true time delay systems based on broadband optical source
      and dispersion components is investigated. It is found that the beat noise
      induced by the optical source begins to dominate and grows far larger than other
      noise terms quickly, as long as the detected optical power is above some certain
      value P(thr). When the system dispersion is nonzero, the output carrier-to-noise
      ratio (CNR) will change periodically with the optical bandwidth due to the noise
      power increment and the dispersion induced radio frequency signal power
      degradation. The maximum CNR is the peak value of the first period. For a set of
      specified system conditions, the P(thr) is calculated to be -21 dBm, and the
      optimal optical bandwidth is 0.8 nm, at which the maximum CNR is 93.3 dB by
      considering the noise in a 1 Hz bandwidth. The results are verified
      experimentally.

PMID- 19183591
TI  - Active control of a 30 m ring interferometric telescope primary mirror.
AB  - The active control of a primary mirror for a ring aperture segmented telescope is
      different from that of a full aperture segmented telescope. Two active
      maintenance proposals for the ring telescope designed from the segmented patterns
      are outlined. We present a preliminary calculation of noise propagation and
      analysis of primary mirror mode characteristics for each proposal. The modulation
      transfer functions (MTFs) of the primary mirror corresponding to each maintenance
      method at several typical working wavelengths are also simulated.

PMID- 19183592
TI  - Characteristic analysis of tapered lens fibers for light focusing and butt
      coupling to a silicon rib waveguide.
AB  - The characteristics of tapered lens fibers (TLFs) are analyzed by using a finite
      difference time-domain (FDTD) method. Two types of TLFs are considered, namely, a
      tapered-cladding TLF and a tapered-core TLF. The radial FDTD method is first used
      to simulate light focusing for these two types of TLFs. It is shown that the
      tapered-core TLF has a smaller focus spot size and a larger transmission loss
      than the tapered-cladding TLF. The butt-coupling between a TLF of either type and
      a Si rib waveguide is then simulated by a three-dimensional FDTD method. The
      tapered-core TLF has a smaller coupling loss to the Si rib waveguide but a
      similar total loss (the sum of the coupling loss and the transmission loss), as
      compared with the tapered-cladding TLF.

PMID- 19183593
TI  - Influence of nonideal chirped fiber Bragg grating characteristics on all-optical
      clock recovery based on the temporal Talbot effect.
AB  - We theoretically and experimentally evaluate the influence of the bandwidth
      limitation and group delay ripple (GDR) of linearly chirped fiber Bragg gratings
      (LCFBGs) on the all-optical clock recovery utilizing the temporal Talbot effect.
      To simulate the reasonably arbitrary shape of the GDR of LCFBGs, the generalized
      distribution function model of GDR was proposed and utilized. The quality of
      recovered clock pulses was evaluated by using the proposed parameters "peak
      variation" and "pulse visibility." Simulation results indicated that both the
      signal pulses with < 1% duty factor and LCFBGs with the bandwidth of >
      approximately 125 times the bit rate, 10 nm for 10 Gbit/s input signal, were
      required to obtain both < approximately 20% peak variation and > approximately 17
      dB pulse visibility of the clock pulses recovered from 2(7)-1 pseudorandom bit
      sequence (PRBS) pulses, and indicated that the LCFBGs with < approximately 20 ps
      peak-to-peak GDR could recover the clock pulses from the 10 Gbit/s signal with
      almost the same quality as that recovered with an ideal LCFBG (with no GDR). In
      addition, it was revealed that < approximately 20 ps peak-to-peak GDR did not
      degrade the timing jitter reduction effect. Qualitative agreement of the
      experimental and simulation results justified our analytical methods. Our
      analytical approach and results will be very useful to practically design the
      LCFBGs for an all-optical clock recovery circuit based on the temporal Talbot
      effect.

PMID- 19183594
TI  - Flat-top and ultranarrow bandpass filter designed by sampled fiber Bragg grating
      with multiple equivalent phase shifts.
AB  - We propose a novel approach to designing an optical filter with a flat-top and
      ultranarrow transmission band by using a sampled fiber Bragg grating (SFBG)
      having multiple equivalent phase shifts (EPSs). In the proposed approach,
      multiple EPSs are fabricated by adjusting several sampling periods of the SFBG.
      The obtained multiple EPSs are then arranged properly to get a flat-top
      transmission band in the narrow -1st reflection band of the SFBG, leading to the
      generation of a flat and ultranarrow transmission band. Filters with two or five
      EPSs are designed by simulation and experiment, with low ripples and ultranarrow
      1 dB bandwidths observed in transmission bands.

PMID- 19183595
TI  - Development of a multiple gas analyzer using cavity ringdown spectroscopy for use
      in advanced fire detection.
AB  - A portable cavity ringdown spectroscopy (CRDS) apparatus was used to detect
      effluents from small test fires in the Fire Emulator/Detector Evaluator (FE/DE)
      and a small room in the Building Fire and Research Laboratory at the National
      Institute of Standards and Technology (NIST). The output from two lasers is
      combined to detect four combustion gases, CO, CO(2), HCN, and C(2)H(2), near
      simultaneously using CRDS. The goal of this work was to demonstrate the
      feasibility of using a CRDS sensor as a fire detector. Fire effluents were
      extracted from several test facilities and measurements of CO, CO(2), HCN, and
      C(2)H(2) were obtained every 25-30 s. In the FE/DE test, peak concentrations of
      the gases from smoldering paper were 420 parts in 10(6) (ppm) CO, 1600 ppm CO(2),
      530 parts in 10(9) (ppb) HCN, and 440 ppb C(2)H(2). Peak gas concentrations from
      the small room were 270 ppm CO, 2100 ppm CO(2), and 310 ppb C(2)H(2).

PMID- 19183596
TI  - Thermoacoustic optical path length stabilization in a single-mode optical fiber.
AB  - We present a simple technique to actively stabilize the optical path length in an
      optical fiber. A part of the fiber is coated with a thin, electrically conductive
      layer, which acts as a heater. The optical path length is thus modified by
      temperature-dependent changes in the refractive index and the mechanical length
      of the fiber. For the first time, we measure the dynamic response of the optical
      path length to the periodic changes of temperature and find it to be in agreement
      with our former theoretical prediction. The fiber's response to the temperature
      changes is determined by the speed of sound in quartz rather than by slow thermal
      diffusion. Making use of this fact, we succeeded in actively stabilizing the
      optical path length with a closed-loop bandwidth of 3.8 kHz.

PMID- 19183597
TI  - Diffractive variable attenuator for femtosecond laser radiation control.
AB  - We present a diffractive phase variable attenuator for femtosecond laser
      radiation control. It allows the control of beam power up to 0.75.10(13) W/cm(2)
      without introducing serious distortions in spectra and beam shape while it
      operates in zero order diffraction. The attenuator can operate with wavelengths
      from DUV to IR.

PMID- 19183598
TI  - Hyperparabolic concentrators.
AB  - We present a family of three-dimensional concentrators constructed from the
      photic field generated by a Lambertian emitter. The profile of these
      concentrators is obtained from the field lines for a two-dimensional truncated
      wedge and is based on the union between a hyperbola and a tilted parabola. By
      revolution of this profile, we obtain hyperparabolic concentrators (HPCs). In the
      limiting case when the focal length of the hyperbola becomes the radius of the
      exit aperture, the HPC becomes the well-known compound parabolic concentrator. On
      the other hand, when the focal length of the hyperbola becomes infinite, the HPC
      achieves the thermodynamic limit of concentration.

PMID- 19183599
TI  - Light scattering calculations exploring sensitivity of depolarization ratio to
      shape changes. I. Single spores in air.
AB  - Calculations of the depolarization ratio, D(Theta, lambda) = 1 - (S22)/(S11), for
      light scattered from an ensemble or cloud of single aerosolized spores in air
      were studied using the discrete dipole approximation (DDA), sometimes also called
      the coupled-dipole approximation. Here S(ij) is the appropriate Mueller matrix
      element for scattering angle Theta and wavelength lambda. The effect of modest
      shape changes on D(Theta, lambda) was determined. The shapes compared were
      prolate ellipsoids versus right circular cylinders joined smoothly to end caps
      consisting of hemispheres of the same diameter as the cylinder. Using the same
      models, the graphs of (S34)/(S11) versus angle were compared with those for
      D(Theta, lambda). The latter shows sensitivity to length in some cases we
      examined, while (S34)/(S11) does not. Size parameters and optical constants
      suggested by measurements of Bacillus cereus endospores were used. An ensemble of
      spores was modeled with prolate spheroids. The results of this model were
      compared with results of a model using the same size and optical parameters, but
      for capped cylinders. The two models produced distinguishably different results
      for the same parameters. In calculations for all the graphs shown, averaging over
      random orientations was performed. Averaging over size distributions similar to
      those from experimental measurements was performed where indicated. The results
      show that measurements of D(Theta, lambda) could be quite useful in
      characterizing the shape of particles in an unknown aerosol and for
      distinguishing between two likely shapes, but not to reconstruct the shapes from
      the graphs alone without additional information.

PMID- 19183600
TI  - Determination of modulation transfer function of a printer by measuring the
      autocorrelation of the transmission function of a printed Ronchi grating.
AB  - We show theoretically and verify experimentally that the modulation transfer
      function (MTF) of a printing system can be determined by measuring the
      autocorrelation of a printed Ronchi grating. In practice, two similar Ronchi
      gratings are printed on two transparencies and the transparencies are
      superimposed with parallel grating lines. Then, the gratings are uniformly
      illuminated and the transmitted light from a large section is measured versus the
      displacement of one grating with respect to the other in a grating pitch
      interval. This measurement provides the required autocorrelation function for
      determination of the MTF.

PMID- 19183601
TI  - Technique for the focal-length measurement of positive lenses using Fizeau
      interferometry.
AB  - We present what we believe is a new technique for the focal-length measurement of
      positive lenses using Fizeau interferometery. The technique utilizes the Gaussian
      lens equation. The image distance is measured interferometrically in terms of the
      radius of curvature of the image-forming wavefront emerging from the lens. The
      radii of curvature of the image-forming wavefronts corresponding to two different
      axial object positions of known separation are measured. The focal length of the
      lens is determined by solving the equations obtained using the Gaussian lens
      equation for the two object positions. Results obtained for a corrected doublet
      lens of a nominal focal length of 200.0 mm with a measurement uncertainty of +/
      2.5% is presented.

PMID- 19183602
TI  - Surface characteristics of an optical component manufactured with a polyurethane
      lap.
AB  - Some interesting small pits/depressions on the surface of optics polished by a
      polyurethane pad are shown and possible reasons for the pits are analyzed. These
      small pits may appear regardless of the material, size, and shape of the optical
      component. The depth of the pits/depressions varies from <0.1lambda (lambda=632.8
      nm) to >0.5lambda and the diameters lie in the range from approximately 1 to
      approximately 3 mm. The reasons the pits/depressions form are discussed; in the
      meantime, some methods to make them shallow are proposed. The pits/depressions
      greatly influence the integrity of optics and, therefore, may deteriorate the
      performance of optical components.

PMID- 19183603
TI  - Wavelength modulation waveforms in laser photoacoustic spectroscopy.
AB  - Different wavelength modulation waveforms were studied comprehensively in tunable
      diode laser photoacoustic spectroscopy. The generation of the photoacoustic
      signal was studied by way of simulations and experiments. A cantilever-enhanced
      photoacoustic detector and CO(2) sample gas were used in the experiments. The
      modulation waveforms compared in this study were sinusoidal, triangular, shaped,
      and quasi-square waves. All four waveforms allow background-free detection of
      trace gases. Compared to the conventionally used sinusoidal modulation, the
      triangular, shaped, and quasi-square waves enhanced the photoacoustic signal by
      factors of 1.12, 1.42, and 1.57, respectively.

PMID- 19183604
TI  - Development of a 1.6 microm differential absorption lidar with a quasi-phase
      matching optical parametric oscillator and photon-counting detector for the
      vertical CO2 profile.
AB  - We have developed a 1.6 microm carbon dioxide (CO(2)) differential absorption
      lidar utilizing a quasi-phase-matching optical parametric oscillator (OPO) and a
      photon-counting detector. The operating wavelengths were chosen based on their
      low interference from water vapor and low temperature sensitivity. The online
      wavelength was in the (30012<--0001) band of CO(2), which was insensitive to
      atmospheric temperature. The established OPO laser achieved a 10 mJ, 200 Hz
      repetition rate at the online and offline wavelengths. Our observations confirmed
      the statistical error of 2% with 5 h of accumulation for the CO(2) density
      profile less than 5.2 km. Also, the statistical error of 1% at an altitude of 2
      km was demonstrated. The results of the vertical CO(2) concentrations acquired
      using a 1.6 microm wavelength are presented.

PMID- 19183606
TI  - Nonlinearly coupled, gain-switched Nd:YAG second harmonic laser with variable
      pulse width.
AB  - An all-solid-state, gain-switched, green laser is developed using a side diode
      array pumped Nd:YAG laser and a KTiOPO(4) (KTP) crystal as an intracavity
      frequency doubler. The effect of nonlinear coupling on the pulse width of the
      fundamental is studied and is found to be in good agreement with the experimental
      measurement. In this preliminary experiment, a peak power of 40 W at 532 nm
      corresponding to a pulse width of 409 ns is obtained for an average pump power of
      2 W. Compared to a Q-switched laser, it is simple and does not require a high
      voltage RF driver or saturable absorbers in its operation. The laser may be
      useful where relatively longer nanosecond pulses are required such as eye
      surgery, micromachining, and underwater communication.

PMID- 19183605
TI  - Paired circularly polarized heterodyne ellipsometer.
AB  - We develop a paired circularly polarized heterodyne ellipsometer (PCPHE), in
      which a heterodyne interferometer based on a two-frequency circularly polarized
      laser beam is set up. It belongs to an amplitude-sensitive ellipsometer that is
      able to provide not only a wider dynamic range of polarization modulation
      frequency but also a higher detection sensitivity than that of a conventional
      photometric ellipsometer. A real-time and precise measurement of ellipsometric
      parameters, which demonstrated an accuracy of less than 1 nm on thickness
      measurement of SiO(2) thin film deposited on silicon substrate, can be applied
      with the PCPHE.

PMID- 19183607
TI  - Temporal wavefront stability of an ultrafast high-power laser beam.
AB  - We measured the temporal dynamics of wavefront aberrations in a beam produced by
      a commercial ultrafast high-power laser with a research-prototype real-time
      Hartmann-Shack wavefront sensor. Measurements were performed at two different
      temporal rates for a 7 mm diameter. Results showed that changes in the wavefront
      aberrations were always lower than 1%. The main contribution to the total root
      mean-square (RMS) wavefront error was due to the effects of low order aberrations
      (defocus and astigmatism), which persisted even after cavity realignment. The
      potential improvement in the beam quality after correction of the different
      aberration modes was also shown. Real-time measurements of laser aberrations
      while modifying cavity parameters might be a useful tool to improve the beam
      quality.

PMID- 19183608
TI  - Surface plasmon resonance of metal nanoparticles sandwiched between dielectric
      layers: theoretical modelling.
AB  - Composite films consisting of a ceramic matrix with embedded metal nanoparticles
      have received increased interest due to their numerous potential applications in
      the field of optics and optoelectronics. Numerous studies have been dedicated to
      the fabrication of these composite materials and it has been shown that
      nanocermet films can be obtained by successive deposition of alternate dielectric
      and metal films of thicknesses opportunely chosen. In this case, stacks of
      dielectric layers alternated with layers of metal nanoclusters (NCs) are
      obtained. However, until now, optical characterization of these kinds of
      multilayer stack has been used to retrieve mainly qualitative information on the
      dimension, shape, and geometric distribution of nanoparticles inside the
      dielectric matrix. An easy-to-handle model that quantitatively links the optical
      properties to the main features of the NCs embedded in the matrix is presented.
      This model can be applied to multilayer stacks of dielectric layers alternated
      with metal NC layers and is shown to be a valid alternative to a recently
      published model [Nanotechnology 19, 125709 (2008)NNOTER0957-448410.1088/0957
      4484/19/22/225302] that was applied to the case of a three-layer structure
      (dielectric/metal:dielectric/dielectric).

PMID- 19183609
TI  - Pointing and tracking errors due to localized distortion induced by a
      transmission-type antenna in intersatellite laser communications.
AB  - A truncated ellipse Gaussian model to express localized distortion is developed
      to a transmission-type optical antenna, based on which the effects of localized
      deformation on pointing and tracking errors are researched. It is shown that
      localized distortion has the greatest influence on pointing and tracking errors
      when distortion deepness h approximately 0.8 lambda, which does not depend on
      other distortion parameters. To reduce the impact of localized deformation on
      pointing and tracking errors, the machining precision of the objective lens of
      the transmission-type antenna should be much better than 0.8 lambda. The
      requirement of the machining precision for lenses is lower than that for mirrors.
      The maxima of pointing and tracking errors due to the localized distortion with
      different radii are given. We hope the results can be used in the design of
      intersatellite optical communication systems.

PMID- 19183610
TI  - Low-speckle laser projection with a broad-area vertical-cavity surface-emitting
      laser in the nonmodal emission regime.
AB  - We demonstrate low-speckle laser projection using a broad-area vertical-cavity
      surface-emitting laser (VCSEL) emitting at 840 nm wavelength as the illumination
      source. By driving the source in a nonmodal emission regime, we were able to
      achieve speckle contrast values as low as 3.5% in a realistic projection setup.
      This was done by driving the VCSEL with specific current pulses without using any
      additional or mechanically moving components to destroy the coherence of the
      laser beam. We quantitatively model the speckle contrast reduction based on
      polarization scrambling and the reduced temporal and spatial coherence of the
      VCSEL.

PMID- 19183611
TI  - Spectrally resolved white-light interferometry for 3D inspection of a thin-film
      layer structure.
AB  - We describe an improved scheme of spectrally resolved white-light interferometry,
      which provides 3D visual inspection of a thin-film layer structure with nanometer
      level resolutions. Compared to the authors' previous method [Appl. Phys. Lett.91,
      091903 (2007)APPLAB0003-695110.1063/1.2776015], 3D tomographic information of
      thin films can be obtained by decoupling the film thickness and top surface
      profile, which is embodied by inducing spectral carrier frequency to the
      reference arm and applying a low-pass filter to the interferogram instead of two
      troublesome measurement steps of activating and deactivating a mechanical
      shutter. We test and verify our proposed method by measuring a patterned thin
      film layer structure as well as standard specimens of thin films with various
      thicknesses.

PMID- 19183612
TI  - Three output port channel-drop filter based on photonic crystals.
AB  - We present a photonic-crystal (PC) channel-drop filter (CDF) design based on 3x3
      PC ring resonators. The normalized transmission spectra for single-ring and dual
      ring configurations have been investigated using two-dimensional finite
      difference time-domain (FDTD) technique in a square-lattice dielectric-rod PC
      structure. First, we investigate a single ring and we show that backward and
      forward dropping is possible in the third communication window. Then we add
      another ring and waveguide to develop a new CDF. This filter consists of an input
      and three outputs. Our FDTD simulation yields more than 85% efficiency over each
      output port.

PMID- 19183613
TI  - 187 W, 3.7 mJ from spectrally combined pulsed 2 ns fiber amplifiers.
AB  - We report on a spectral combination of four 2 ns pulsed fiber amplifier systems
      to a total output power of 187 W at a 50 kHz repetition rate resulting in >3.7 mJ
      of pulse energy and 1.7 MW of pulse peak power. A dielectric reflection grating
      is used to merge the four individual beams to one output with close to
      diffraction-limited beam quality independent of the power level. The output
      characteristics are beyond the capabilities of a single emitter and further
      scaling in a straightforward way appears to be feasible.

PMID- 19183614
TI  - Laser beam shaping using a single-mode fiber abrupt taper.
AB  - A new beam-shaping device was realized by an abrupt taper with a length of
      approximately 700 microm and a waist of approximately 40 microm. The insertion
      loss of the device is less than 3%. The diameter of the flat beam top can be up
      to approximately 900 microm with a small intensity variation (4%) and a small
      half-divergence angle (2.5 degrees). The conversion efficiency of the new device
      from a Gaussian-shaped to a flat-top profile is comparable with that of a long
      period-gratings-based device, while keeping the fabrication cost low. The new
      device requires only a fusion splicer and standard SMF-28 fiber, eliminating the
      need for photolithographic procedures. The new device also has no obvious
      incident light polarization dependence.

PMID- 19183615
TI  - In vivo photosensitizer tomography inside the human prostate.
AB  - Interstitial photodynamic therapy (IPDT) provides a promising means to treat
      large cancerous tumors and solid organs inside the human body. The treatment
      outcome is dependent on the distributions of light, photosensitizer, and tissue
      oxygenation. We present a scheme for reconstructing the spatial distribution of a
      fluorescent photosensitizer. The reconstruction is based on measurements
      performed in the human prostate, acquired during an ongoing IPDT clinical trial,
      as well as in optical phantoms. We show that in an experimental setup we can
      quantitatively reconstruct a fluorescent inclusion in a fluorescent background.
      We also show reconstructions from a patient showing a heterogeneous distribution
      of the photosensitizer mTHPC in the human prostate.

PMID- 19183616
TI  - Soft x-ray microscope constructed with a PMMA phase-reversal zone plate.
AB  - A soft x-ray microscope based on a phase-reversal zone plate was constructed and
      tested using high harmonic radiation as a coherent light source. The 61st
      harmonic centered at 13.3 nm was optimized in spectral sharpness and intensity by
      controlling the incident laser energy and chirp. A phase-reversal zone plate made
      of polymethyl methacrylate more than doubled the first-order efficiency. The nano
      patterns, imaged on an x-ray CCD with a magnification of 650, showed that the
      measured resolution of the microscope was better than 100 nm.

PMID- 19183617
TI  - Intracavity dispersion effect on timing jitter of ultralow noise mode-locked
      semiconductor based external-cavity laser.
AB  - We report the generation of optical pulse trains with 380 as of residual timing
      jitter (1 Hz-1 MHz) from a mode-locked external-cavity semiconductor laser,
      through a combination of optimizing the intracavity dispersion and utilizing a
      high-power, low-noise InGaAsP quantum-well slab-coupled optical waveguide
      amplifier gain medium. This is, to our knowledge, the lowest residual timing
      jitter reported to date from an actively mode-locked laser.

PMID- 19183618
TI  - Synthesis of picosecond pulses by spectral compression and shaping of femtosecond
      pulses in engineered quadratic nonlinear media.
AB  - Narrow-bandwidth picosecond pulses of predetermined spectral and temporal shapes
      are generated with high efficiency by frequency conversion of femtosecond pulses
      in lithium tantalate crystals with engineered quasi-phase-matching structures. We
      give examples of the synthesis of Gaussian and super-Gaussian picosecond pulses
      and also of a pair of synchronized phase-coherent picosecond pulses with a
      predetermined carrier-frequency difference.

PMID- 19183619
TI  - Experimental study of the interaction between localized and propagating surface
      plasmons.
AB  - The interaction between localized and propagating surface plasmons is
      investigated in a structure consisting of a two-dimensional periodic gold
      nanoparticle array, an SiO2 spacer, and a gold film. The resonance wavelengths of
      the two types of surface plasmons supported by the structure are tailored by
      changing the gold nanoparticle size and the array period. An anticrossing of the
      resonance positions is observed in the reflection spectra, demonstrating the
      strong coupling between localized and propagating surface plasmons.

PMID- 19183620
TI  - Monolithic 100 mW Yb waveguide laser fabricated using the femtosecond-laser
      direct-write technique.
AB  - A femtosecond-laser-written monolithic waveguide laser (WGL) oscillator based on
      a distributed-feedback architecture and fabricated in ytterbium-doped phosphate
      glass is reported. The device lased at 1033 nm with an output power of 102 mW and
      a bandwidth of less than 2 pm when bidirectionally pumped at 976 nm. The WGL
      device was stable and operated for 50 h without degradation. This demonstration
      of a high-performance WGL opens the possibility for creating a variety of narrow
      linewidth laser designs in bulk glasses.

PMID- 19183621
TI  - Two-step-only quadrature phase-shifting digital holography.
AB  - Conventional methods of quadrature phase-shifting holography require two
      holograms and either intensity distribution of the reference wave or that of the
      object wave to reconstruct an original object without the zero order and the twin
      image noise in an on-axis holographic recording setup. We present a technique
      called two-step-only quadrature phase-shifting holography in which solely two
      quadrature-phase holograms are required. Neither reference-wave intensity nor an
      object-wave intensity measurement is needed in the technique.

PMID- 19183622
TI  - All-fiber Fabry-Perot resonators based on microfiber Sagnac loop mirrors.
AB  - We demonstrate all fiber Fabry-Perot resonators (F-P resonators) based on Sagnac
      loop mirrors assembled with tellurite microfibers. As-assembled F-P resonators,
      with dimensions of hundreds of micrometers, show clear resonant responses with
      typical quality factor of about 5700, free spectral range of about 1 nm, and a
      maximum extinction ratio of 18 dB. The reflectivity of the loop mirror and the
      effective cavity length of the F-P resonator can be tuned by micromanipulation
      under an optical microscope. F-P resonators demonstrated here show advantages of
      small size, good resonance, easy fabrication, tunability, and easy integration
      with fiber systems.

PMID- 19183623
TI  - Broadband amplitude squeezing in a periodically poled KTiOPO4 waveguide.
AB  - We generated -2.2 dB of broadband amplitude squeezing at 1064 nm in a
      periodically poled KTiOPO4 (PPKTP) waveguide by coupling of the fundamental and
      second-harmonic cw fields. This is the largest amount of squeezing obtained to
      date in a KTP waveguide, limited by propagation losses. This result paves the way
      for further improvements by use of lower-loss buried ion-exchanged waveguides.

PMID- 19183624
TI  - Simple integrated single-atom detector.
AB  - We present a reliable and robust integrated fluorescence detector capable of
      detecting single atoms. The detector consists of a tapered lensed single-mode
      fiber for precise delivery of excitation light and a multimode fiber to collect
      the fluorescence. Both are mounted in lithographically defined SU-8 holding
      structures on an atom chip. 87Rb atoms propagating freely in a magnetic guide are
      detected with an efficiency of up to 66%, and a signal-to-noise ratio in excess
      of 100 is obtained for short integration times.

PMID- 19183625
TI  - High-efficiency 20-50 kHz mid-infrared orientation-patterned GaAs optical
      parametric oscillator pumped by a 2 microm holmium laser.
AB  - We report on what are, to our knowledge, the best results obtained with an
      orientation-patterned GaAs optical parametric oscillator (OPO) pumped by a Q
      switched 2 microm Ho:YAG laser. Up to 2.85 W are obtained for 6.1 W of pump
      power, corresponding to an optical-to-optical conversion efficiency of 46.5% with
      a threshold of 1 W. Optical damage occurred at a fluence of about 2 J/cm2. The
      thickness of the crystal limited the pump power. Slope efficiencies are of the
      same order as those obtained with ZnGeP2 OPOs pumped with the same Ho:YAG laser.

PMID- 19183626
TI  - Radial and azimuthal beam parameters.
AB  - Global invariant parameters are introduced to characterize the radial and
      azimuthal content of totally polarized beams. Such parameters are written in
      terms of the second moments of the optical beam and are invariant in propagation
      through symmetric first-order optical systems described by the ABCD matrix. Since
      it was proven in the past that the usual definition for radial polarization is
      not invariant, such invariance is novel in characterizing the radial and
      azimuthal polarizations content of optical beams. The possibility of obtaining a
      pure mode from a given beam using the proposed parameters is discussed.

PMID- 19183627
TI  - Nonexistence of entanglement sudden death in dephasing of high NOON states.
AB  - We study the dynamics of entanglement in continuous variable quantum systems.
      Specifically, we study the phenomena of entanglement sudden death (ESD) in
      general two-mode-N-photon states undergoing pure dephasing. We show that for
      these circumstances, ESD never occurs. These states are generalizations of the so
      called high NOON states (i.e., a superposition of N photons in the first mode, O
      in the second, with O photons in the first, N in the second), shown to decrease
      the Rayleigh limit of lambda to lambda/N, which promises great improvement in
      resolution of interference patterns if states with large N are physically
      realized [Phys. Rev. Lett.85, 2733 (2000)]. However, we show that in dephasing
      NOON states, the time to reach some critical visibility Vcrit, scales inversely
      with N2. On the practical level, this shows that as N increases, the visibility
      degrades much faster, which is likely to be a considerable drawback for any
      practical application of these states.

PMID- 19183628
TI  - Microscopy of extreme ultraviolet lithography masks with 13.2 nm tabletop laser
      illumination.
AB  - We report the demonstration of a reflection microscope that operates at 13.2 nm
      wavelength with a spatial resolution of 55+/-3 nm. The microscope uses
      illumination from a tabletop extreme ultraviolet laser to acquire aerial images
      of photolithography masks with a 20 s exposure time. The modulation transfer
      function of the optical system was characterized.

PMID- 19183629
TI  - Terahertz wire-grid polarizers with micrometer-pitch Al gratings.
AB  - We fabricated a terahertz wire-grid polarizer consisting of a micrometer-pitch Al
      grating on a Si substrate by photolithography and wet etching. The ratio of TM
      and TE transmittances (extinction ratio) was over 35 dB at 0.5 THz. At the
      Brewster angle of the Si substrate, the polarization transmittance of a TM wave
      through the fabricated polarizer exceeded 95% and the extinction ratio was over
      45 dB at approximately 1 THz. The fabricated polarizer has a higher extinction
      ratio than conventional free-standing terahertz wire-grid polarizers.

PMID- 19183630
TI  - Beyond the frame rate: measuring high-frequency fluctuations with light-intensity
      modulation.
AB  - Power-spectral-density measurements of any sampled signal are typically
      restricted by both acquisition rate and frequency response limitations of
      instruments, which can be particularly prohibitive for video-based measurements.
      We have developed a new method called intensity modulation spectral analysis that
      circumvents these limitations, dramatically extending the effective detection
      bandwidth. We demonstrate this by video tracking an optically trapped microsphere
      while oscillating an LED illumination source. This approach allows us to quantify
      fluctuations of the microsphere at frequencies over 10 times higher than the
      Nyquist frequency, mimicking a significantly higher frame rate.

PMID- 19183631
TI  - Adiabaticity criterion and the shortest adiabatic mode transformer in a coupled
      waveguide system.
AB  - By analyzing the propagating behavior of the supermodes in a coupled-waveguide
      system, we have derived a universal criterion for designing adiabatic mode
      transformers. The criterion relates epsilon, the fraction of power scattered into
      the unwanted mode, to waveguide design parameters and gives the shortest possible
      length of an adiabatic mode transformer, which is approximately 2/piepsilon1/2
      times the distance of maximal power transfer between the waveguides. The results
      from numerical calculations based on a transfer-matrix formalism support this
      theory very well.

PMID- 19183632
TI  - Multipole surface solitons in thermal media.
AB  - We address the existence and properties of multipole solitons localized at a
      thermally insulating interface between uniform or layered thermal media and a
      linear dielectric. We find that in the case of uniform media, only surface
      multipoles with less than three poles can be stable. In contrast, we reveal that
      periodic alternation of the thermo-optic coefficient in layered thermal media
      makes possible the stabilization of higher-order multipoles.

PMID- 19183633
TI  - Supercontinuum generation in planar glass membrane fibers: comparison with bulk
      media.
AB  - Planar glass membrane fibers (PGMFs) are of current interest owing to the fact
      that they combine the interesting dispersive properties of fibers with
      diffraction in one unbound transverse dimension. We study supercontinuum (SC)
      spectra generated in PGMFs and show that the underlying dynamics has similarities
      to bulk medium. At the same time, the rich dispersion properties of PGMFs open up
      new possibilities, including SC spectral shapes that do not occur in natural bulk
      media. In all cases, the SC spectra in PGMFs can be interpreted in detail using
      the effective-three-wave-mixing model originally developed for bulk media.

PMID- 19183635
TI  - Compact, diode-side-pumped Nd3+:YLiF4 laser at 1053 nm with 45% efficiency and
      diffraction- limited quality by mode controlling.
AB  - We demonstrate what we believe to be the highest efficiency obtained to date in a
      transversely diode-pumped Nd3+:YLiF4 slab laser operating at 1053 nm. The compact
      11-cm-long laser cavity configuration is based on total internal reflection of
      the intracavity beam at the pump facet of the gain crystal to improve the overlap
      with the pump radiation. Multimode operation with 9.5 W of output power and an
      efficiency of 45% is obtained for 21 W of pump power in a single-pass
      configuration. Using a second pass through the crystal and a new mode-controlling
      technique, the beam quality is improved to the diffraction limit with 6.9 W of
      output power and 33% of optical-to-optical efficiency.

PMID- 19183636
TI  - Observation of two-dimensional nonlocal gap solitons.
AB  - We demonstrate, both theoretically and experimentally, the existence of nonlocal
      gap solitons in two-dimensional periodic photonic structures with defocusing
      thermal nonlinearity. We employ liquid-infiltrated photonic crystal fibers and
      show how the system geometry can modify the effective response of a nonlocal
      medium and the properties of two-dimensional gap solitons.

PMID- 19183634
TI  - Combined hyperspectral and spectral domain optical coherence tomography
      microscope for noninvasive hemodynamic imaging.
AB  - We have combined hyperspectral imaging with spectral domain optical coherence
      tomography (SDOCT) to noninvasively image changes in hemoglobin saturation, blood
      flow, microvessel morphology, and sheer rate on the vessel wall with tumor
      growth. Changes in these hemodynamic variables were measured over 24 h in dorsal
      skin fold window chamber tumors. There was a strong correlation between
      volumetric flow and hemoglobin saturation (rho=0.89, p=9x10(-6), N=15) and a
      moderate correlation between shear rate on the vessel wall and hemoglobin
      saturation (rho=0.56, p=0.03, N=15).

PMID- 19183637
TI  - Electrical tunable random laser emission from a liquid-crystal infiltrated
      disordered planar microcavity.
AB  - Here we report electric-field-induced, wavelength-tunable random lasing action in
      a liquid-crystal infiltrated disordered planar microcavity. With the increasing
      of external voltage from 0 V to 30 V, the emission wavelength of the random laser
      was continuously tuned from 648 nm to 597 nm. It was also tuned back to 648 nm
      again by reducing the voltage back to 0 V.

PMID- 19183638
TI  - Enhancement of flip-chip white light-emitting diodes with a one-dimensional
      photonic crystal.
AB  - A design for a one-dimensional photonic crystal (1D PhC) based on thin-film
      optics is proposed to improve the light extraction efficiency of phosphor
      converted flip-chip white-light-emitting diodes (LEDs). The 1D PhC thin film
      consisting of alternating layers of TiO2 and SiO2 is added between a phosphor
      layer and sapphire substrate of the LEDs. Monte Carlo simulation method is
      introduced to analyze performance of the proposed LEDs with a 1D PhC. Results
      show that the light extraction efficiency is higher than that of conventional
      LEDs by 16%, and the correlated color temperature becomes lower, below 4000 K.
      These improvements are attributed to the efficient extraction of backscattered
      light from the phosphor layer by using the 1D PhC thin film.

PMID- 19183639
TI  - Photobleaching resistance of stimulated parametric emission in microscopy.
AB  - Photobleaching of organic fluorescent labels is a ubiquitous problem in
      fluorescence microscopy, limiting imaging capabilities and presenting hurdles to
      quantitative biophysical measurements. We report here that a nonlinear optical
      signal from some organic fluorophores persists in the presence of photobleaching.
      Specifically, a four-wave mixing process that is enhanced by a two-photon
      absorption resonance in the target fluorophore, termed stimulated parametric
      emission (SPE), is essentially unaffected by the photobleaching of the
      fluorophore, for rhodamine 6G and other commercial green and red fluorophores.
      The stability of the SPE signal, and the ability to image weakly or
      nonfluorescent chromophores, should make this nonlinear microscopy useful for
      quantitative biophysical measurements.

PMID- 19183641
TI  - Wavelength-selective directional coupling with dielectric-loaded plasmonic
      waveguides.
AB  - We consider wavelength-selective splitting of radiation using directional
      couplers (DCs) formed by dielectric-loaded surface-plasmon-polariton waveguides
      (DLSPPWs). The DCs were fabricated by depositing sub-wavelength-sized polymer
      ridges on a gold film using large-scale UV photolithography and characterized at
      telecommunications wavelengths with near-field microscopy. We demonstrate a
      DLSPPW-based 45-microm-long DC comprising 3 microm offset S bends and 25-microm
      long parallel waveguides that changes from the "through" state at 1500 nm to 3 dB
      splitting at 1600 nm, and show that a 50.5-microm-long DC should enable complete
      separation of the radiation channels at 1400 and 1620 nm. The DC performance is
      found to be in good agreement with full vectorial three-dimensional finite
      element simulations.

PMID- 19183640
TI  - Optical nonlinearities of Au nanoparticles and Au/Ag coreshells.
AB  - Au nanoparticles exhibited both negative and positive nonlinear absorptions with
      ground-state plasmon bleaching and free-carrier absorption that could be origins
      of the saturable and reverse-saturable optical properties. Au/Ag coreshells
      displayed only positive nonlinear absorption and reverse-saturable optical
      properties as a function of excitation intensity at the edge of surface-plasmon
      resonance, which implies no ground-state plasmon bleaching and the existence of
      two-photon absorption.

PMID- 19183642
TI  - Repetition-rate-tunable return-to-zero and carrier-suppressed return-to-zero
      optical pulse train generation using a polarization modulator.
AB  - An approach is proposed to generating return-to-zero (RZ) and carrier-suppressed
      return-to-zero (CS-RZ) pulse trains with a high and tunable repetition rate by
      using a polarization modulator (PolM). The PolM is a special phase modulator that
      can support both TE and TM modes with opposite phase modulation indices. A
      linearly polarized cw light with its polarization state oriented with an angle of
      45 degrees to one principal axis of the PolM is modulated by a sinusoidal signal
      at the PolM. The output light from the PolM is then sent to a polarization beam
      splitter (PBS), with one axis of the PBS aligned at an angle of 45 degrees to one
      principle axis of the PolM. At the two outputs of the PBS, two optical signals
      with one consisting of the even-order optical sidebands and the other consisting
      of the odd-order optical sidebands are obtained, leading to the generation of an
      RZ and a CS-RZ pulse train having a repetition rate that is twice the frequency
      of the drive sinusoidal signal. The proposed approach is demonstrated by a proof
      of-concept experiment in which an RZ and a CS-RZ pulse train with tunable
      repetition rates of 7.2 and 8 GHz are generated.

PMID- 19183643
TI  - Optical-data storage-readout technique based on fractal encrypting masks.
AB  - We propose the use of fractal structured diffractive masks as keys in secure
      storage-readout systems. A joint transform correlator based on a photorefractive
      crystal in the Fourier domain is implemented to perform encryption and
      decryption. We discuss the advantages of encrypting information using this kind
      of deterministic keys in comparison to conventional random phase masks.
      Preliminary experimental results are presented to demonstrate the effectiveness
      of the proposed system.

PMID- 19183644
TI  - Normalized Born ratio for fluorescence optical projection tomography.
AB  - We present a normalized Born approach for fluorescence optical projection
      tomography that takes into account tissue absorption properties. This approach
      can be particularly useful to study fluorochrome distribution within tissue. We
      use the algorithm to three-dimensionally reconstruct and characterize a
      fluorescein isothiocyanate containing absorptive phantom and an infarcted mouse
      heart previously injected with a fluorescent molecular probe.

PMID- 19183645
TI  - Ultrasensitive photonic crystal fiber refractive index sensor.
AB  - We introduce a microfluidic refractive index sensor based on a directional
      coupler architecture using solid-core photonic crystal fibers. The sensor
      achieves very high sensitivity by coupling the core mode to a mode in the
      adjacent fluid-filled waveguide that is beyond modal cutoff, and with strong
      field overlap. We demonstrate the device through the selective infiltration of a
      single hole with fluid along a microstructured optical fiber. A detection limit
      of 4.6x10(-7) refractive index units has been derived from measurements with a
      sensitivity of 30,100 nm per refractive index unit, which is the highest for a
      fiber device to date.

PMID- 19183646
TI  - Widely transparent electrodes based on ultrathin metals.
AB  - Transparent electrodes made of single-component ultrathin (<10 nm) metal films
      (UTMFs) are obtained by sputtering deposition. We show that the optical
      transparency of the deposited films (chromium and nickel) is comparable to that
      of indium tin oxide (ITO) in the visible and near-infrared range (0.4-2.5
      microm), while it can be significantly higher in the ultraviolet (175-400 nm) and
      mid-infrared (2.5-25 microm) regions. Despite their very small thickness, the
      deposited UTMFs are also uniform and continuous over the 10 cm substrate, as it
      is confirmed by the measured low electrical resistivity. The excellent optical
      and electrical properties, stability, compatibility with active materials,
      process simplicity, and potential low cost make UTMFs high-quality transparent
      electrodes for the optoelectronics industry, seriously competing with widely used
      transparent conductive oxides, such as ITO.

PMID- 19183647
TI  - Lasing and optical gain around 500 nm from optically pumped lasers grown on c
      plane GaN substrates.
AB  - Using the variable stripe length method we demonstrated positive net optical gain
      around 500 nm for an optically pumped laser with InGaN/GaN multiple quantum wells
      grown on c-plane freestanding GaN substrates. We found that owing to low optical
      gain, reducing optical losses is crucial to increasing lasing wavelength. We
      demonstrated lasing at 502 nm by using a 3-mm-long cavity with cleaved facets.

PMID- 19183648
TI  - Impulse attack free double-random-phase encryption scheme with randomized lens
      phase functions.
AB  - Security of the conventional Fourier-based double-random-phase encryption (DRPE)
      technique is prone to impulse attacks, as the Fourier transform (FT) of a delta
      function results in a unity function. To negate such an attack, the phase factors
      of the lenses are modified by multiplying these with random-phase functions.
      Owing to this modification of the FT as a result of the randomized lens phase
      function, a modified FT (MFTLR) gives the random output for a delta function
      input. Employing MFTLR in the DRPE technique enhances the security features and
      makes the encryption system safer from the impulse attack. Numerical and
      experimental results are given for the validation of the proposed technique.

PMID- 19183649
TI  - All-optical Hilbert transformer based on a single phase-shifted fiber Bragg
      grating: design and analysis.
AB  - A simple all-fiber design for implementing an all-optical temporal Hilbert
      transformer is proposed and numerically demonstrated. We show that an all-optical
      Hilbert transformer can be implemented using a uniform-period fiber Bragg grating
      (FBG) with a properly designed amplitude-only grating apodization profile
      incorporating a single pi phase shift in the middle of the grating length. All
      optical Hilbert transformers capable of processing arbitrary optical waveforms
      with bandwidths up to a few hundreds of gigahertz can be implemented using
      feasible FBGs.

PMID- 19183650
TI  - Study of self-focusing effect induced by femtosecond photodisruption on model
      substances.
AB  - We have studied the possible nonlinear effects on tissue and model substance with
      emphasis on self-focusing effect. The nature of this effect and its biological
      consequences are discussed. We have studied how the self-focusing action changes
      with applied laser power and its effect on various depths of the biological
      materials. Critical power for biological material is calculated, and the peak
      power required for surgical purposes is found to be greater than the critical
      power. Furthermore, we discuss other possible effects that self-focusing might
      have on refractive surgery.

PMID- 19183651
TI  - Quantifying the paraxiality for laser beams from the M2 factor.
AB  - A useful relationship among the parameter called paraxial estimator [Opt. Lett.
      32, 927 (2007)] and two parameters concerning the beam quality, the M2 factor,
      and the beam spot size was derived. This relationship allows one to quantify the
      paraxiality for a monochromatic laser beam from standard measurements extending
      the applicability of such an estimator for real beams even if the beam profile
      shape does not have a closed-form representation. Hence, the paraxial estimator
      might be a suitable tool for deepening the analysis on the quality of a laser
      beam.

PMID- 19183653
TI  - Directional random-laser emission from Bragg gratings with irregular
      perturbation.
AB  - Here we report the laser actions inside an active organic-inorganic grating with
      some irregular perturbation. In an optical excitation experiment, band-edge and
      random-laser emissions were both observed. The laser thresholds of the two laser
      actions are very close, which shows that random laser sometimes can operate with
      a threshold comparable to band-edge emission. Owing to the diffraction of the
      grating, directional emission with a narrow divergence angle was also obtained.

PMID- 19183654
TI  - Low-noise simultaneous fluorescence detection of two atomic states.
AB  - We demonstrate a new simultaneous normalized detection technique for fluorescence
      detection of ultracold atoms in a superposition of ground-state hyperfine levels.
      Using this technique we observe atom shot-noise limited detection signal-to-noise
      ratios in excess of 7800:1 per shot and 14400:1 in 1 s.

PMID- 19183655
TI  - Surface plasmon polariton discrete diffraction compensation.
AB  - We report on the observation of discrete diffraction in surface plasmon polariton
      waveguide arrays at a wavelength of 1550 nm. We also adopt the effective index
      method to reduce our simulation geometry to two-dimensions, predict the spread of
      single-waveguide excitation in parallel waveguide arrays, and explore changing
      the excitation angle to detune the waveguides. Our experimental results show
      discrete diffraction compensation at an angle of 2.2 degrees as predicted by
      simulations.

PMID- 19183656
TI  - Fast electroholographic switching.
AB  - Electroholographic switching with a rise time of 13 ns is henceforth presented.
      The switching was demonstrated in a potassium lithium tantalate crystal doped
      with copper and titanium with Tc=10 degrees C. The crystal was operated at 17
      degrees C. The switching operation was done in the g11/g12 configuration, in
      which the Bragg condition remains fulfilled at all levels of the applied field.
      As electroholography is a wavelength-selective switching method, this opens the
      way for implementing optical packet switching and fast wavelength addressing
      schemes in optical fiber networks that apply wavelength division multiplexing.

PMID- 19183657
TI  - Voltage-controlled Kerr effect in magnetophotonic crystal.
AB  - A magneto-optical tunable device based on a one-dimensional magnetophotonic
      crystal infiltrated with a nematic liquid crystal has been proposed. By applying
      a tunable electric field the voltage-induced reorientation of the director
      results in an alternating magneto-optical effect. The transfer matrix method was
      performed to verify the controllable magneto-optical properties. The present
      results may be useful for future application of liquid crystal-based tunable
      magneto-optical devices.

PMID- 19183658
TI  - Experimental observation of slow mode dispersion in photonic crystal coupled
      cavity waveguides.
AB  - We experimentally investigate the dispersion curve of an integrated silicon-on
      insulator coupled-cavity waveguide in a photonic crystal environment using a
      technique based on far-field imaging. We show that a chain of eight coupled
      cavities of a moderate Q factor can form a continuous dispersion band
      characterized by extremely flat dispersion and a group index of 105+/-20 within a
      2.6 nm wavelength range. The experimental results are well reproduced by
      theoretical calculations based on the guided-mode expansion method.

PMID- 19183659
TI  - Fast-fluorescence dynamics in nonratiometric calcium indicators.
AB  - The fluorescence decay of high-affinity nonratiometric Ca2+ indicator Oregon
      Green BAPTA-1 (OGB-1) is analyzed with unprecedented temporal resolution in the
      two-photon excitation regime. A triple exponential decay is shown to best fit the
      fluorescence dynamics of OGB-1. We provide a model for accurate measurements of
      the free Ca2+ concentration and dissociation constants of nonratiometric calcium
      indicators.

PMID- 19183660
TI  - Different forms of wavelength polarization switching and bistability in a 1.55
      microm vertical-cavity surface-emitting laser under orthogonally polarized
      optical injection.
AB  - Different forms of wavelength polarization switching and bistability are reported
      in a 1550 nm vertical-cavity surface-emitting laser (VCSEL) operated just above
      threshold and subject to orthogonally polarized optical injection into the
      subsidiary orthogonal polarization mode. This diversity of behavior at the
      wavelength of 1550 nm offers promise for the use of VCSELs in optical signal
      processing and optical switching applications.

PMID- 19183661
TI  - Retardation-induced plasmonic blinking in coupled nanoparticles.
AB  - We study how retardation leads to interference effects in radiatively coupled
      plasmonic nanoparticles. We show that inclined illumination through a glass
      substrate on two plasmonic particles results in either an enhanced field or an
      attenuated field localized at the position of the first particle. Periodic
      intensity blinking of the first particle is observed as a function of the
      particle separation. This phenomenon is nonsymmetric, and almost no blinking is
      observed on the second particle. The effect is strongest when the illumination
      angle is chosen such that the optical retardation path in the substrate coincides
      with the particle distance. Implications of this plasmonic blinking for near
      field measurements are discussed.

PMID- 19183662
TI  - Total internal reflection without change of polarization using a right-angle
      prism with half-wavelength-thick optical interference coating.
AB  - Monochromatic light, which is polarized in an arbitrary state, is totally
      internally reflected at angle of incidence phi=45 degrees without change of
      polarization by a right-angle prism of refractive index n0=1+1/Square root of
      2=1.70711 (e.g., N-LAK8 Schott glass at wavelength lambda=706 nm), which is
      coated with a transparent thin film of refractive index n1=(1+1/2)1/2=1.30656
      (e.g., vacuum-deposited fluoride material) and of metric thickness equal to half
      of the vacuum wavelength of incident light, d=lambda/2. The ambient medium of
      evanescent refraction is assumed to be vacuum, air, or an inert gas. Wavelength
      shifts of +/-50 nm, or changes of the internal angle of incidence of +/-1 degrees
      around 45 degrees, cause phase errors of only a few degrees. The reflected and
      incident polarization states are nearly identical in the presence of such small
      phase errors.

PMID- 19183663
TI  - Fermat's principle and the formal equivalence of local light-ray rotation and
      refraction at the interface between homogeneous media with a complex refractive
      index ratio.
AB  - We derive a formal description of local light-ray rotation in terms of complex
      refractive indices. We show that Fermat's principle holds, and we derive an
      extended Snell's law. The change in the angle of a light ray with respect to the
      normal of a refractive index interface is described by the modulus of the
      refractive index ratio; the rotation around the interface normal is described by
      the argument of the refractive index ratio.

PMID- 19183664
TI  - Four-wave-mixing coherent oscillator with frequency shifted feedback and
      misaligned pump waves.
AB  - The effect of the pump waves misalignment on the oscillation spectra and
      oscillation intensity of a semilinear photorefractive oscillator is studied
      numerically and compared with the results of the experiment performed with a
      KNbO3:Fe,Ag crystal.

PMID- 19183665
TI  - Rational phase mask to extend the depth of field in optical-digital hybrid
      imaging systems.
AB  - We propose a novel phase mask called the rational phase mask (RPM) to extend the
      depth of field in optical-digital hybrid imaging systems. Using the invariance to
      defocus of the modulation transfer function as the merit function, we adopt the
      simulated annealing algorithm to optimize the RPM together with the other three
      existing phase masks. Numerical comparisons prove the RPM's superiority.

PMID- 19183666
TI  - Experimental demonstration of a cross-order echelle grating triplexer based on an
      amorphous silicon nanowire platform.
AB  - We present the design, fabrication, and characterization of an ultracompact
      silicon-on-insulator-based echelle grating triplexer. It is based on the cross
      order design, which utilizes different diffraction orders to cover a large
      spectral range from 1.3 to 1.5 microm with three channels located at 1310, 1490,
      and 1550 nm and with a footprint of 150 micromx130 microm.

PMID- 19183667
TI  - Simple heterodyne laser interferometer with subnanometer periodic errors.
AB  - We describe a simple heterodyne laser interferometer that has subnanometer
      periodic errors and is applicable to industrial fields. Two spatially separated
      beams can reduce the periodic errors, and the use of a right-angle prism makes
      the optical configuration much simpler than previous interferometers. Moreover,
      the optical resolution can be enhanced by a factor of 2, because the phase change
      direction is opposite between reference and measurement signals. Experiments have
      demonstrated the periodic errors are less than 0.15 nm owing to the frequency
      mixing of the optical source. The improvements for reducing the frequency mixing
      of the optical system are also discussed.

PMID- 19183668
TI  - Goos-Hanchen and Imbert-Fedorov shifts of polarized vortex beams.
AB  - We study, analytically and numerically, reflection and transmission of an
      arbitrarily polarized vortex beam on an interface separating two dielectric media
      and derive general expressions for linear and angular Goos-Hanchen (GH) and
      Imbert-Fedorov shifts. We predict a novel vortex-induced GH shift and also reveal
      a direct connection between the spin-induced angular shifts and the vortex
      induced linear shifts.

PMID- 19183669
TI  - Refractive index sensor based on surface-plasmon interference.
AB  - We propose a refractive index sensor based on the interference of two surface
      plasmon waves on both surfaces of a gold film with a two-slit structure. The
      phase of the interference was solved, and the dispersion relation of the real
      part of Au dielectric function was considered. The sensor was performed with NaCl
      H2O solutions of different concentrations and exhibited a linear response and a
      high sensitivity of 4547 nm/RIU (refractive index unit) to the refractive index
      change.

PMID- 19183670
TI  - Directionality of Gaussian array beams propagating in atmospheric turbulence.
AB  - The angular spread is chosen as the characteristic parameter of beam
      directionality, and the directionality of Gaussian array beams propagating in
      atmospheric turbulence is studied. The consistency of the directionality of
      Gaussian array beams expressed in terms of the angular spread and the normalized
      far-field average intensity distribution is also examined. Closed-form
      expressions for the mean-squared beam width and angular spread of Gaussian array
      beams propagating in atmospheric turbulence are derived. It is found that for the
      case of coherent combination, under a certain condition array beams exist that
      may have the same directionality (i.e., the same angular spread) as a fully
      coherent Gaussian laser beam in free space and also in turbulence. However, the
      directionality of Gaussian array beams in terms of the angular spread is not
      consistent with that in terms of the normalized far-field average intensity
      distribution in free space, whereas they may be consistent as a result of
      turbulence.

PMID- 19183673
TI  - Three-dimensional object-distortion-tolerant recognition for integral imaging
      using independent component analysis.
AB  - Independent component analysis (ICA) aims at extracting unknown components from
      multivariate data assuming that the underlying components are mutually
      independent. This technique has been successfully applied to the recognition and
      classification of objects. We present a method that combines the benefits of ICA
      and the ability of the integral imaging technique to obtain 3D information for
      the recognition of 3D objects with different orientations. Our recognition is
      also possible when the 3D objects are partially occluded by intermediate objects.

PMID- 19183674
TI  - Scanning holographic microscopy with spatially incoherent sources: reconciling
      the holographic advantage with the sectioning advantage.
AB  - A new mode of operation of scanning holographic microscopy that combines the two
      seemingly incompatible holographic advantage and axial sectioning advantage is
      proposed and demonstrated. Temporally modulated Fabry-Perot fringes are scanned
      in a two-dimensional raster over the specimen. With a spatially coherent (point)
      source, the fringes are spatially nonlocalized and encode the entire three
      dimensional volume of the specimen in the form of a single-sideband in-line
      Fresnel hologram. With an extended spatially incoherent source the fringes are
      axially localized and select the modulated information from a specific axial
      plane only. The holographic advantage and the sectioning advantage can thus be
      achieved with the same scanning holographic setup using different source sizes.

PMID- 19183675
TI  - Exact off-resonance near fields of small-size extended hemielliptic 2-D lenses
      illuminated by plane waves.
AB  - The near fields of small-size extended hemielliptic lenses made of rexolite and
      isotropic quartz and illuminated by E- and H-polarized plane waves are studied.
      Variations in the focal domain size, shape, and location are reported versus the
      angle of incidence of the incoming wave. The problem is solved numerically in a
      two-dimensional formulation. The accuracy of results is guaranteed by using a
      highly efficient numerical algorithm based on the combination of the Muller
      boundary integral equations, the method of analytical regularization, and the
      trigonometric Galerkin discretization scheme. The analysis fully accounts for the
      finite size of the lens as well as its curvature and thus can be considered as a
      reference solution for other electromagnetic solvers. Moreover, the trusted
      description of the focusing ability of a finite-size hemielliptic lens can be
      useful in the design of antenna receivers.

PMID- 19183676
TI  - Optical aberrations described by an alternative series expansion.
AB  - Aberrations of optical systems are usually analyzed by decomposing the wavefront
      aberration at a pupil into a series of terms. The Seidel and Zernike series are
      two common examples, each with its own strengths and weaknesses. A new aberration
      series is proposed that combines some of the strengths of each. The new series is
      consistent with the traditional system of aberration types but enables the
      straightforward characterization and comparison of different optical systems,
      independent of pupil size or shape. Expressions for the conversion between the
      new and common aberration series are given, and the physical interpretations of
      the different aberrations are discussed.

PMID- 19183677
TI  - Classical versus complex fractional Fourier transformation.
AB  - The quantum optical complex fractional Fourier transform (FRFT) has been related
      to the classical FRFT using both classical and quantum formalisms. In particular,
      it was shown that the kernel of the complex FRFT can be classically produced with
      rotated astigmatic optical systems that mimic the quantum entanglement property.

PMID- 19183678
TI  - Multipole expansion of Bessel and Gaussian beams for Mie scattering calculations.
AB  - Multipole expansions of Bessel and Gaussian beams, suitable for use in Mie
      scattering calculations, are derived. These results allow Mie scattering
      calculations to be carried out considerably faster than existing methods,
      something that is of particular interest for time evolution simulations where
      large numbers of scattering calculations must be performed. An analytic result is
      derived for the Bessel beam that improves on a previously published expression
      requiring the evaluation of an integral. An analogous expression containing a
      single integral, similar to existing results quoted, but not derived, in
      literature, is derived for a Gaussian beam, valid from the paraxial limit all the
      way to arbitrarily high numerical apertures.

PMID- 19183679
TI  - Wiener reconstruction of undersampled imagery.
AB  - We derive a Fourier-domain Wiener filter for the reconstruction of undersampled
      imagery. The filter differs from previous implementations in that it permits
      adjustment of the trade-offs between sharpness of the reconstruction, noise
      amplification, and aliasing artifact suppression. Additionally, a net transfer
      function that characterizes the combined effects of the imaging system and the
      reconstruction process is derived. This net transfer function is valid for both
      unaliased and aliased spatial frequencies. The expression for the net transfer
      function is applicable to more general linear image sharpening algorithms.

PMID- 19183680
TI  - Analysis of the light extraction efficiency of light-emitting diodes with
      photonic crystals combined with the generalized Rouard method.
AB  - The light extraction efficiency of light-emitting diodes (LEDs) patterned with
      photonic crystals is investigated based on an incoherent multi-reflection
      transmission model. The formulas of the extraction efficiency are obtained in an
      analytic form similar to the unpatterned case. Besides, we generalize the Rouard
      formulas commonly used in thin-film optics to the case of multilayered photonic
      crystal slabs. The influence of various types of backside reflectors and the
      absorption of the semiconductor on the efficiency are demonstrated for GaN-based
      LEDs. The optimization of the photonic crystal slab based on the LED model is
      also presented and briefly discussed.

PMID- 19183681
TI  - Design of diffractive lenses that generate optical nulls without phase
      singularities.
AB  - We exploit a technique, based on nonlinear optimization, to design diffractive
      lenses that focus optical nulls without any phase singularities. To ensure ease
      of fabrication, these lenses are composed of concentric circular zones.
      Furthermore, we show that this technique is readily extended to multiple
      wavelengths and can be used to improve tolerance to fabrication errors.

PMID- 19183682
TI  - Physical optics modeling of 2D dielectric lenses.
AB  - We propose an advanced physical optics formulation for the accurate modeling of
      dielectric lenses used in quasi-optical systems of millimeter, submillimeter, and
      infrared wave applications. For comparison, we obtain an exact full-wave solution
      of a two-dimensional lens problem and use it as a benchmark for testing and
      validation of asymptotic models being considered.

PMID- 19183683
TI  - Scintillation-induced jitter of projected light with centroid trackers.
AB  - When light radiating from a distant object passes through extended turbulence,
      the light is scintillated. Such scintillated light may be received by an optical
      system and passed to a camera in the focal plane, and used to track an object.
      Such trackers often use centroid trackers. Then a laser or other light may be
      projected back toward the object, steered by the centroid measured on the
      tracker. The presence of scintillation on the tracker return will cause a jitter
      error in the pointing of projected light, if the projected light's intensity
      differs from that of the incoming scintillation pattern. This error is caused by
      a lack of full-field conjugation of the tilt component of the received return.
      This error is considered, for horizontal path conditions, as a difference between
      centroid tilt and gradient tilt. The estimated error is typically not large, and
      is estimated by both simulation and analytic means, and these are found to agree
      for conditions of interest. The possibility of means for correction of this error
      is discussed briefly.

PMID- 19183684
TI  - Ray-optics analysis of inhomogeneous biaxially anisotropic media.
AB  - Firm evidence of the biaxial nematic phase in liquid crystals, not induced by a
      magnetic or electric field, has been established only recently. The discovery of
      these biaxially anisotropic liquid crystals has opened up new areas of both
      fundamental and applied research. The advances in biaxial liquid-crystal-related
      topics call for a good overview on the propagation of waves through biaxially
      anisotropic media. Although the literature sporadically discusses biaxial
      interfaces, the propagation of waves through inhomogeneous biaxially anisotropic
      bulk materials has never been fully addressed. For this reason, we present a
      novel ray-tracing method for inhomogeneous biaxially anisotropic media. In the
      geometrical-optics approach, we clearly show how to assess the optical properties
      of inhomogeneous biaxially anisotropic media in three dimensions.

PMID- 19183685
TI  - Rigorous expressions for the Fresnel equations at interfaces between absorbing
      media.
AB  - When conventional Fresnel theory is applied to absorbing multilayer systems, a
      slight discrepancy with respect to the principle of conservation of energy
      arises. Here we solve this long-perceived problem and present rigorous
      expressions for the Fresnel equations generally applicable to interfaces between
      isotropic absorbing media. These equations satisfy the conservation law
      automatically and coincide naturally with the conventional ones in reflection by
      simple mirrors placed in a vacuum.

PMID- 19183686
TI  - Ray tracing of an aspherical lens with antireflective subwavelength structured
      surfaces.
AB  - A method of ray tracing for an aspherical lens with subwavelength periodic
      structured surfaces has been developed. The ray tracing in the antireflective
      subwavelength structure is based on the group velocity of the Bloch wave.
      Transmittance and phase delay for the surface structure are determined with
      rigorous coupled wave analysis. Calculated wavefront aberration was smaller than
      20 mlambda for an aspherical lens with numerical aperture of 0.6. For a lens with
      a higher numerical aperture, the wavefront aberrations increase drastically.

PMID- 19183687
TI  - Moving object detection based on shape prediction.
AB  - Statistical analysis is widely used for moving object detection from video
      sequences, and generally it assumes that the recent segmentations are the
      desirable samples. However, we think the recent segmentations are not desirable
      for the detection of deformable objects, such as a pedestrian. We present an
      object detection framework that is designed to select the most desirable samples
      from all historical segmentations for statistical analysis. Central to this
      algorithm is that the shape evolution of the deformable object is learned from
      historical segmentations by an autoregressive model. Based on the learned model,
      the shape of the moving object in a current frame is predicted. Those historical
      segmentations that show similar shape to the predicted shape are selected for
      statistical analysis instead of the recent segmentations. Definitive experiments
      demonstrate the performance of the proposed method.

PMID- 19183688
TI  - Fractional Fourier transform of Lorentz-Gauss beams.
AB  - Lorentz-Gauss beams are introduced to describe certain laser sources that produce
      highly divergent beams. The fractional Fourier transform (FRFT) is applied to
      treat the propagation of Lorentz-Gauss beams. Based on the definition of
      convolution and the convolution theorem of the Fourier transform, an analytical
      expression for a Lorentz-Gauss beam passing through an FRFT system has been
      derived. By using the derived expression, the properties of a Lorentz-Gauss beam
      in the FRFT plane are graphically illustrated with numerical examples.

PMID- 19183689
TI  - Reflectance and transmittance model for recto-verso halftone prints: spectral
      predictions with multi-ink halftones.
AB  - We extend a previously proposed spectral reflectance and transmittance prediction
      model for recto-verso prints to the case of multi-ink halftones. The model takes
      into account the multiple reflections and the lateral propagation of light within
      the paper substrate (optical dot gain) as well as the spreading of the inks
      according to their superposition conditions (mechanical dot gain). The model
      accounts for the orientation of the incident and exiting lights when traversing
      the halftone ink layers, which enables modeling the measuring geometry. The
      equations for the calibration of the model and for the predictions are presented
      in detail. Several experiments with inkjet prints show that the multi-ink
      halftone transmittance model is as accurate as the actually most performing
      reflectance models for halftone prints.

PMID- 19183690
TI  - Optimized effective permittivity to improve imaging resolution of multilayered
      structures in the infrared.
AB  - Two periodic structures with different effective impedances, both comprising
      alternate layers of a positive and a negative permittivity material, are
      considered in the infrared. We find that the Fabry-Perot resonance effect
      periodically influences the sharpness of subwavelength focusing as the total
      thicknesses of the two structures increase, especially for the impedance-matched
      structure. On the basis of the improved multilayered structures, we design an
      optimized structure (i.e., the effective impedance is chosen between 0 and 1) for
      which a higher resolution less than lambda/12 (lambda is the wavelength in the
      air) can be obtained through weighing the advantages and disadvantages of the two
      different multilayered structures and choosing appropriate surface terminations.

PMID- 19183691
TI  - Statistics of spatially integrated speckle intensity difference.
AB  - We consider the statistics of the spatially integrated speckle intensity
      difference obtained from two separated finite collecting apertures. For fully
      developed speckle, closed-form analytic solutions for both the probability
      density function and the cumulative distribution function are derived here for
      both arbitrary values of the mean number of speckles contained within an aperture
      and the degree of coherence of the optical field. Additionally, closed-form
      expressions are obtained for the corresponding nth statistical moments.

PMID- 19183693
TI  - Scintillation index of modified Bessel-Gaussian beams propagating in turbulent
      media.
AB  - The scintillation index is formulated for modified Bessel-Gaussian beams
      propagating in weakly turbulent media. Numerical calculations applied directly to
      the derived triple integral show that, for off-axis positions, the modified
      Bessel-Gaussian beams of higher than zero order scintillate less than Gaussian
      beams at large input beam sizes and low beam orders with the increasing width
      parameter initially contributing positively to this phenomenon of less
      scintillation. As the beam order exceeds two, this advantage is diminished. The
      modified Bessel-Gaussian beam of order zero is a special case, however,
      exhibiting lowest scintillation at small input beam sizes. When considered
      against the propagation length, higher-order modified Bessel-Gaussian beams
      continue to offer less scintillation than those of order zero. At various radial
      positions, the scintillation index of modified Bessel-Gaussian beams with orders
      higher than zero attains small values toward the beam edges but rises sharply
      when approaching the beam axis. The effect of inner and outer scales of
      turbulence is also studied, and it is found that while increasing the inner scale
      of turbulence seems to cause increases in scintillation, the influence of the
      outer scale is hardly noticeable.

PMID- 19183692
TI  - Partially coherent illumination in full-field interferometric synthetic aperture
      microscopy.
AB  - A model is developed for optical coherence tomography and interferometric
      synthetic aperture microscopy (ISAM) systems employing full-field frequency
      scanned illumination with partial spatial coherence. This model is used to derive
      efficient ISAM inverse scattering algorithms that give diffraction-limited
      resolution in regions typically regarded as out of focus. Partial spatial
      coherence of the source is shown to have the advantage of mitigating multiple
      scattering effects that can otherwise produce significant artifacts in full-field
      coherent imaging.

PMID- 19183694
TI  - Nanoscale shift of the intensity distribution of dipole radiation.
AB  - The energy flow lines (field lines of the Poynting vector) for radiation emitted
      by a dipole are in general curves, rather than straight lines. For a linear
      dipole the field lines are straight, but when the dipole moment of a source
      rotates, the field lines wind numerous times around an axis, which is
      perpendicular to the plane of rotation, before asymptotically approaching a
      straight line. We consider an elliptical dipole moment, representing the most
      general state of oscillation, and this includes the linear dipole as a special
      case. Due to the spiraling near the source, for the case of a rotating dipole
      moment, the field lines in the far field are displaced with respect to the
      outward radial direction, and this leads to a shift of the intensity distribution
      of the radiation in the far field. This shift is shown to be independent of the
      distance to the source and, although of nanoscale dimension, should be
      experimentally observable.

PMID- 19183695
TI  - Multispectral intensity diffraction tomography: single material objects with
      variable densities.
AB  - A reconstruction theory for multispectral intensity diffraction tomography (I-DT)
      is established and investigated for use with single material objects whose
      dispersion characteristics are known a priori. Instead of varying the object-to
      detector distance, as prescribed by the original I-DT method and other classic in
      line holographic reconstruction methods, the temporal frequency of the
      illuminating plane wave represents the degree of freedom of the imaging system
      that is varied to acquire two independent intensity measurements at each
      tomographic view angle. Unlike previous multispectral I-DT methods, the proposed
      method does not require a nondispersive assumption. A computer-simulation study
      is presented to demonstrate and corroborate the method.

PMID- 19183696
TI  - Phase-shift estimation in sinusoidally illuminated images for lateral
      superresolution.
AB  - Sinusoidally patterned illumination has been used to obtain lateral
      superresolution and axial sectioning in images. In both of these techniques
      multiple images are taken with the object illuminated by a sinusoidal pattern,
      the phase of the sinusoidal illumination being shifted differently in each image.
      The knowledge of these phase shifts is critical for image reconstruction. We
      discuss a method to estimate this phase shift with no prior knowledge of the
      shifts. In postprocessing we estimate randomly introduced, unknown phase shifts
      and process the images to obtain a superresolved image. Results of computer
      simulations are shown.

PMID- 19183697
TI  - Mass detection on mammograms: influence of signal shape uncertainty on human and
      model observers.
AB  - We studied the influence of signal variability on human and model observers for
      detection tasks with realistic simulated masses superimposed on real patient
      mammographic backgrounds and synthesized mammographic backgrounds (clustered
      lumpy backgrounds, CLB). Results under the signal-known-exactly (SKE) paradigm
      were compared with signal-known-statistically (SKS) tasks for which the observers
      did not have prior knowledge of the shape or size of the signal. Human observers'
      performance did not vary significantly when benign masses were superimposed on
      real images or on CLB. Uncertainty and variability in signal shape did not
      degrade human performance significantly compared with the SKE task, while
      variability in signal size did. Implementation of appropriate internal noise
      components allowed the fit of model observers to human performance.

PMID- 19183698
TI  - Achieving resolution beyond the diffraction limit of telescopic optics with
      remote masking.
AB  - The resolution of a telescope is traditionally limited by the size of its
      aperture and the associated diffraction limit. Increases in resolving power
      invariably require larger apertures. The dependence of resolution on a telescope
      size can be completely removed, however, by a technique referred to as remote
      masking. This technique involves the use of a small occulting object that is
      positioned to mask a portion of the target. The drop in total target intensity of
      the unresolved object corresponds directly to the brightness of the area being
      masked. Moving the mask in front of the target modulates the total observed
      intensity. The observer can thus create an image having a resolution comparable
      to the angular size of the mask. The concept was validated through a one
      dimensional experiment, where two light sources were successfully resolved at an
      angular separation well below the diffraction limit of the telescope. The
      theoretical resolving power of a remotely masked telescope is limited only by the
      size of, and distance to, the occulting mask.

PMID- 19183699
TI  - Estimating chromophore distributions from multiwavelength photoacoustic images.
AB  - Biomedical photoacoustic tomography (PAT) can provide qualitative images of
      biomedical soft tissue with high spatial resolution. However, whether it is
      possible to give accurate quantitative estimates of the spatially varying
      concentrations of the sources of photoacoustic contrast-endogenous or exogenous
      chromophores-remains an open question. Even if the chromophores' absorption
      spectra are known, the problem is nonlinear and ill-posed. We describe a
      framework for obtaining such quantitative estimates. When the optical scattering
      distribution is known, adjoint and gradient-based optimization techniques can be
      used to recover the concentration distributions of the individual chromophores
      that contribute to the overall tissue absorption. When the scattering
      distribution is unknown, prior knowledge of the wavelength dependence of the
      scattering is shown to be sufficient to overcome the absorption-scattering
      nonuniqueness and allow both distributions of chromophore concentrations and
      scattering to be recovered from multiwavelength photoacoustic images.

PMID- 19183700
TI  - A System for Multiplexed Direct Electrical Detection of DNA Synthesis.
AB  - An electronic system for the multiplexed detection of DNA polymerization is
      designed and characterized. DNA polymerization is detected by the measurement of
      small transient currents arising from ion diffusion during polymerization. A
      transimpedance amplifier is used to detect these small currents; we implemented a
      twenty-four channel recording system on a single printed circuit board. Various
      contributions to the input-referred current noise are analyzed and characterized,
      as it limits the minimum detectable current and thus the biological limit of
      detection. We obtained 8.5 pA RMS mean noise current (averaged over all 24
      channels) over the recording bandwidth (DC to 2 kHz). With digital filtering, the
      input-referred current noise of the acquisition system is reduced to 2.4 pA,
      which is much lower than the biological noise. Electrical crosstalk between
      channels is measured, and a model for the crosstalk is presented. Minimizing the
      crosstalk is critical because it can lead to erroneous microarray data. With
      proper precautions, crosstalk is reduced to a negligible value (less than 1.4%).
      Using a micro-fabricated array of 24 gold electrodes, we demonstrated system
      functionality by detecting the presence of a target DNA oligonucleotide which
      hybridized onto its corresponding target.

PMID- 19183701
TI  - Patients' Experiences of Being a Burden on Family in Terminal Illness.
AB  - Studies of persons with chronic and life-threatening illness have revealed a fear
      of being a burden on family. The purpose of this case study was to explore that
      concern in-depth in three persons with different terminal illnesses. Participants
      were part of a larger study of end-of-life decision making and were selected for
      this study because their illnesses are characterized by a steady decline in
      health (amyotrophic lateral sclerosis), a rapid decline (stage IV lung cancer),
      or an uncertain trajectory of decline (advanced heart failure). Content analysis
      of their interviews resulted in four themes: managing the burden, spirituality,
      supportive relationships, and planning for the future. Themes contained specific
      categories of thoughts, feelings, and actions related to fear of being a burden.
      These themes should be explored in greater depth in future larger studies of
      persons with terminal illness.

PMID- 19183702
TI  - A Cycloaddition Strategy for Use toward Berkelic Acid, an MMP Inhibitor and
      Potent Anticancer Agent Displaying a Unique Chroman Spiroketal Motif.
AB  - A kinetically controlled diastereoselective cycloaddition between a chiral enol
      ether and an ortho-quinone methide (o-QM) produces a chroman spiroketal motif
      that is found in the core of berkelic acid, a novel matrix metalloproteinase
      (MMP) inhibitor and potent anticancer agent. The transformation lays the
      groundwork for preparation of future inhibitors aimed at distinguishing among the
      active sites of the twenty-three known MMP. Experimental findings suggest that
      the stereochemistry that emerges from cycloaddition is opposite that which
      results from thermodynamic ketalization.

PMID- 19183703
TI  - Housing environment and mental health outcomes: A levels of analysis perspective.
AB  - This study examines the effects of perceived housing environment on selected well
      being outcomes of a seriously mentally ill population in supported housing
      programs. Individuals live independently in their own apartments and use
      supportive mental health services as needed. The study conceptualizes one's
      housing environment as existing at the apartment, neighborhood and the
      surrounding community levels of analysis that, taken together, form a multi
      dimensional construct of housing environment. Self-report data from interviews
      with a sample of seriously mentally ill adults is paired with (a) observer
      ratings of housing environments, (b) census profiles of the surrounding community
      and (c) case manager ratings of clients' functioning in order to explore the
      effects of supported housing environments on well-being outcomes. Well-being is
      operationalized here as levels of psychiatric distress, recovery orientation,
      residential satisfaction, and adaptive functioning. Hierarchical regression
      models posit that apartment, neighborhood and census tract level variables are
      unique predictors of these domains of well-being. Results show that neighborhood
      level variables, especially those relating to the social environment, are the
      most influential predictors for understanding variance in well-being, with
      apartment level variables also contributing to understanding of housing
      environment effects. The census tract level predictors did not contribute a
      significant amount of explanation of the variance in well-being outcomes.
      Implications for supported housing programs and the role of ecological levels of
      analysis in conceptualizing and measuring housing environment influence are
      discussed.

PMID- 19183705
TI  - Head, Neck, and Eye Movements That Modulate Tinnitus.
AB  - Recent functional brain imaging studies in humans suggest that the neural
      generator(s) for tinnitus may reside in the central nervous system and involve
      both auditory as well as nonauditory centers. The contribution of nonauditory
      centers in the pathogenesis and regulation of tinnitus is reinforced by studies
      showing that many patients have somatic tinnitus whereby movements and
      manipulations of the eyes, head, neck, jaw, and shoulder can modulate the
      loudness and pitch of their tinnitus. In most cases, the maneuvers lead to
      increases in tinnitus loudness or pitch rather than decreases. Our results
      indicate that most tinnitus patients experience only a modest change in loudness
      or pitch when performing these maneuvers. However, some patients report that
      these maneuvers significantly modulate the loudness or pitch, sometimes by a
      factor of 2 to 3. The high prevalence of somatic tinnitus serves to illustrate
      the complex multimodal interactions that exist between the auditory pathway and
      other sensory-motor systems innervating the head, neck, shoulders, and eyes.

PMID- 19183704
TI  - Stereoselective Synthesis of Saturated Heterocycles via Pd-Catalyzed Alkene
      Carboetherification and Carboamination Reactions.
AB  - The development of Pd-catalyzed carboetherification and carboamination reactions
      between aryl/alkenyl halides and alkenes bearing pendant heteroatoms is
      described. These transformations effect the stereoselective construction of
      useful heterocycles such as tetrahydrofurans, pyrrolidines, imidazolidin-2-ones,
      isoxazolidines, and piperazines. The scope, limitations, and applications of
      these reactions are presented, and current stereochemical models are described.
      The mechanism of product formation, which involves an unusual intramolecular syn
      insertion of an alkene into a Pd-Heteroatom bond is also discussed in detail.

PMID- 19183706
TI  - The SRI24 Multi-Channel Brain Atlas: Construction and Applications.
AB  - We present a new standard atlas of the human brain based on magnetic resonance
      images. The atlas was generated using unbiased population registration from high
      resolution images obtained by multichannel-coil acquisition at 3T in a group of
      24 normal subjects. The final atlas comprises three anatomical channels (T(1)
      weighted, early and late spin echo), three diffusion-related channels (fractional
      anisotropy, mean diffusivity, diffusion-weighted image), and three tissue
      probability maps (CSF, gray matter, white matter). The atlas is dynamic in that
      it is implicitly represented by nonrigid transformations between the 24 subject
      images, as well as distortion-correction alignments between the image channels in
      each subject. The atlas can, therefore, be generated at essentially arbitrary
      image resolutions and orientations (e.g., AC/PC aligned), without compounding
      interpolation artifacts. We demonstrate in this paper two different applications
      of the atlas: (a) region definition by label propagation in a fiber tracking
      study is enabled by the increased sharpness of our atlas compared with other
      available atlases, and (b) spatial normalization is enabled by its average shape
      property. In summary, our atlas has unique features and will be made available to
      the scientific community as a resource and reference system for future imaging
      based studies of the human brain.

PMID- 19183707
TI  - A generalized simulation description language.
AB  - Our group supports two emission tomography simulation packages: SimSET, which is
      in the public domain, and ASIM, which we are planning to re-engineer and release
      as open-source software. Currently the inputs and outputs for the two programs,
      though conceptually similar, have very different formats. We are creating a
      common input meta-language for SimSET and ASIM. We plan to make this language
      general enough that it will be suitable for other emission tomography simulation
      packages. This language will make it easier for users to use multiple simulation
      packages and will facilitate definition of similar simulations for various
      packages.

PMID- 19183708
TI  - ANALYSIS OF HEPATITIS C VIRUS INFECTION MODELS WITH HEPATOCYTE HOMEOSTASIS.
AB  - Recently, we developed a model for hepatitis C virus (HCV) infection that
      explicitly includes proliferation of infected and uninfected hepatocytes. The
      model predictions agree with a large body of experimental observations on the
      kinetics of HCV RNA change during acute infection, under antiviral therapy, and
      after the cessation of therapy. Here we mathematically analyze and characterize
      both the steady state and dynamical behavior of this model. The analyses
      presented here are important not only for HCV infection but should also be
      relevant for modeling other infections with hepatotropic viruses, such as
      hepatitis B virus.

PMID- 19183709
TI  - MEASUREMENT EQUIVALENCE OF NEIGHBORHOOD QUALITY MEASURES FOR EUROPEAN AMERICAN
      AND MEXICAN AMERICAN FAMILIES.
AB  - The factorial and construct equivalence of subscales assessing parents' and
      children's perceptions of the quality of their neighborhood was examined in
      Mexican American and European American families. All subscales (dangerous people
      in the neighborhood, sense of safety in the neighborhood, quality of the physical
      environment) demonstrated adequate partial factorial invariance across English-
      and Spanish-speaking Mexican American and European American families. Reports by
      children about dangerous people in the neighborhood was the closest to achieving
      strict factorial invariance, and the only one of the four dimensions to achieve
      invariance in the validity analyses across Mexican American and European American
      families. The implications of using these self-report neighborhood quality
      measures in studies of multiple cultural or language groups are discussed.

PMID- 19183710
TI  - Conflict Resolution in Mexican American Adolescents' Friendships: Links with
      Culture, Gender and Friendship Quality.
AB  - This study was designed to describe the conflict resolution practices used in
      Mexican American adolescents' friendships, to explore the role of cultural
      orientations and values and gender-typed personality qualities in conflict
      resolution use, and to assess the connections between conflict resolution and
      friendship quality. Participants were 246 Mexican American adolescents (M = 12.77
      years of age) and their older siblings (M = 15.70 years of age). Results
      indicated that adolescents used solution-oriented strategies most frequently,
      followed by nonconfrontation and control strategies. Girls were more likely than
      boys to use solution-oriented strategies and less likely to use control
      strategies. Familistic values and gender-typed personality qualities were
      associated with solution-oriented conflict resolution strategies. Finally,
      conflict resolution strategies were related to overall friendship quality:
      solution-oriented strategies were positively linked to intimacy and negatively
      associated with friendship negativity, whereas nonconfrontation and control
      strategies were associated with greater relationship negativity.

PMID- 19183711
TI  - Suspected abusive head trauma: Guidelines for a multidisciplinary approach.

PMID- 19183712
TI  - Nasal continuous positive airway pressure and outcomes in preterm infants: A
      retrospective analysis.
AB  - OBJECTIVE: The aim of the present retrospective study was to describe the use of
      nasal continuous positive airway pressure (NCPAP) and the prevalence of
      bronchopulmonary dysplasia (BPD). STUDY DESIGN: Data from 1526 neonates with
      gestational age less than 32 weeks, admitted to Children's and Women's Health
      Centre of British Columbia (Vancouver, British Columbia) between period 1 (1996
      to 2000) and period 2 (2000 to 2004) were analyzed. The use of respiratory
      therapies and outcomes were retrospectively compared before and after the
      introduction of a NCPAP approach to respiratory support. RESULTS: A significant
      increase in the use of NCPAP was noted between periods 1 and 2 (60% versus 71%),
      as well as a significant reduction in the use of surfactant (50% versus 41%),
      postnatal steroids (30% versus 10%) and the need for mechanical ventilation (77%
      versus 64%). In period 2, there was a significant reduction in the prevalence of
      BPD at 28 days (33% versus 26%), higher prevalence of severe retinopathy of
      prematurity (3% versus 6%) and less periventricular leukomalacia (4% versus 2%).
      CONCLUSIONS: A significant increase in the use of NCPAP therapy in the neonatal
      unit has been associated with a decrease in the use of more invasive therapies.
      The incidence of BPD has decreased if defined as need for supplemental oxygen at
      28 days of age, but not when the 36 weeks' postconceptional age criterion was
      used. NCPAP therapy may decrease the use of more invasive therapies and may
      improve respiratory outcomes. The impact of this intervention on nonrespiratory
      outcomes warrants further investigation.

PMID- 19183713
TI  - 'I want to lose weight': Early risk for disordered eating?
AB  - The present study examined the risk of disordered eating and its relation to
      attempts to lose weight by surveying a Maritime Canadian sample of 247 girls and
      boys in grades 6, 7 and 8. Current attempts to lose weight were highest in grade
      8 girls (41% of girls and 9% of boys) compared with grade 6 (14% of girls and 24%
      of boys) and grade 7 (21% of girls and 13% of boys) children. Of those trying to
      lose weight, 71.4% were in the average range for weight and height, 12.2% were
      overweight and 16.3% were obese. The Children's version of the Eating Attitudes
      Test (ChEAT) was used to assess eating attitudes and behaviours, and the
      Rosenberg Self-Esteem Scale was used as a measure of self-esteem. The results
      showed that 8.5% of the children fell in the high-risk group for disordered
      eating (ChEAT score 20 or higher). Those in the high-risk group were
      significantly more likely to fear being overweight (90%), to have tried to lose
      weight in the past (81%), to be currently trying to lose weight (76%), and to
      have engaged in binge eating (38%) and self-induced vomiting (24%). The best
      predictor of membership in the high-risk group for girls was current attempts at
      weight loss and having lower self-esteem. Only two boys fell in the high-risk
      group. Body mass index and current weight category (underweight, average,
      overweight and obese) could not explain the differences between the low- and high
      risk groups. Knowing that a child is trying to lose weight can aid in identifying
      youth at risk for disordered eating, and can provide an opportunity for
      preventive education.

PMID- 19183715
TI  - Magnets in the bowel: A sticky problem!

PMID- 19183716
TI  - Doctors and medical industry.

PMID- 19183714
TI  - Anthropometric and metabolic characteristics in children with clinically
      diagnosed nonalcoholic fatty liver disease.
AB  - BACKGROUND: Childhood obesity is currently approaching epidemic proportions
      worldwide. Various chronic diseases are associated with obesity, but nonalcoholic
      fatty liver disease (NAFLD) has received little attention from paediatricians.
      AIM: To examine anthropometric and metabolic variables relevant to NAFLD disease
      mechanism and severity. METHODS: A retrospective review of 53 consecutive
      paediatric patients clinically diagnosed with NAFLD was performed between 1997
      and 2004. Variables studied included ethnicity, body mass index, acanthosis
      nigricans, aspartate aminotransferase and alanine amino-transferase levels, and
      fasting levels of glucose, insulin and lipids. Insulin resistance was quantified
      by validated models (the homeostasis model of insulin resistance [HOMA-IR] and
      the quantitative insulin-sensitivity check index [QUICKI]). RESULTS: The cohort
      was comprised of 34 boys and 19 girls; there was a 2:1 male predominance. The
      mean age of the children was 13.5 years (median 14.2 years; range 5.6 to 18.9
      years), and 13 were 11 years of age or younger. Forty-five per cent were
      Caucasian, 30% Asian and 21% Hispanic. Thirty-eight children (72%) were
      classified as obese and 11 children (21%) were classified as overweight, with a
      mean ideal body weight percentage of 150.9+/-4.2 (range 67% to 226%) and a BMI Z
      score of 1.9+/-0.1 (range -1.2 to 3.2). Hyperinsulinemia was present in 35
      children (66%). Insulin resistance (HOMA-IR 9.8+/-2.6, abnormal if greater than
      3) was associated with increased plasma triglyceride (P=0.03) and total
      cholesterol (P=0.04) levels. These parameters were significant irrespective of
      alanine aminotransferase or aspartate aminotransferase levels. CONCLUSIONS:
      Hyperlipidemia with hyperinsulinemia and insulin resistance in overweight and
      obese children with fatty liver may be important signs of liver dysfunction in
      childhood NAFLD, irrespective of serum aminotransferases. In overweight or obese
      children with hyperlipidemia or insulin resistance, evaluation for NAFLD is
      warranted.

PMID- 19183717
TI  - Case 1: The case of the irritable nephrotic.

PMID- 19183718
TI  - Case 2: Long-standing neuropathy with acute onset of weakness.

PMID- 19183719
TI  - What is the evidence for the safety and efficacy of over-the-counter cough and
      cold preparations for children younger than six years of age?

PMID- 19183721
TI  - Re: The relationship between childhood behaviour disorders and unintentional
      injury events.

PMID- 19183720
TI  - Re: The relationship between childhood behaviour disorders and unintentional
      injury events.

PMID- 19183722
TI  - Special considerations for the health supervision of children and youth in foster
      care.

PMID- 19183724
TI  - Extra-label drug use in food-producing animals in Canada.

PMID- 19183726
TI  - Extra-label drug use in food-producing animals in Canada.

PMID- 19183729
TI  - One world, one health, one medicine.

PMID- 19183730
TI  - Veterinary medical ethics. An ethicist's commentary on large volume practices
      undercutting smaller practices on vaccine prices.

PMID- 19183731
TI  - Twin pregnancy experimental model for transvaginal ultrasound-guided twin
      reduction in mares.
AB  - Multiple pregnancies are still an important cause of noninfectious abortion,
      stillbirth, neonatal mortality, and significant delays in reproductive
      performance in mares. Despite new management techniques, reduction in multiple
      pregnancies is an ongoing preoccupation and challenge for the equine
      veterinarian. The aim of the present study was to establish a twin pregnancy
      experimental model in the mare to study the effectiveness of a transvaginal
      ultrasound-guided embryonic vesicle injection. Mares in heat were inseminated and
      then received an embryo at day 7 of the estrous cycle. At days 14 and 30, 53.5%
      (n = 23) and 23% (n = 10) of the mares, respectively, were carrying twins. Twin
      pregnancies were reduced at day 30 by transvaginal ultrasound-guided puncture of
      the embryonic vesicle (control, n = 5) or by transvaginal ultrasound-guided
      injection (TVUEVI) of 25 mg of amikacin into the embryonic vesicle (n = 5). The
      TVUEVI treatment had a 40% success rate and no significant variations in
      progesterone and prostaglandin metabolite were observed. Even though the
      technique does not seem very effective, the experimental model could be useful
      for clinical research in embryo reduction and early embryonic loss.

PMID- 19183732
TI  - Unsuccessful treatment of a horse with mandibular granulomatous osteomyelitis due
      to Halicephalobus gingivalis.
AB  - An 8-year-old horse was presented with a submandibular swelling. Biopsy of the
      lesion indicated granulomatous osteomyelitis due to Halicephalobus gingivalis. In
      the absence of evidence of involvement of the central nervous system at the time
      of diagnosis, the horse was treated with ivermectin. Unfortunately, the horse did
      not survive.

PMID- 19183733
TI  - A survey of antimicrobial use during bovine abdominal surgery by western Canadian
      veterinarians.
AB  - Members of the Western Canadian Association of Bovine Practitioners were surveyed
      regarding their use of antimicrobials in bovine abdominal surgery. Perioperative
      antimicrobials were used in 100% of abdominal surgeries by 96 of 98 respondents.
      Although postoperative administration was the most common perioperative period
      for antimicrobial use, intraoperative intraperitoneal use was reported by more
      than half of the veterinarians surveyed. Procaine penicillin G and
      oxytetracycline were the most commonly administered perioperative antimicrobials.

PMID- 19183734
TI  - Clinical Mycoplasma bovis mastitis in prepubertal heifers on 2 dairy herds.
AB  - Findings of herd investigations of heifers with prepubertal mastitis are
      presented. Mycoplasma bovis was isolated from lacteal secretions and tissue
      samples of necropsied heifers; the same strain infected dams and herd mates.
      Vertical transmission is suggested in this first report of intramammary
      infections of M. bovis in peripubertal heifers.

PMID- 19183735
TI  - Infertility associated with persistent hymen in an alpaca and a llama.
AB  - Perforation and dilation of the persistent hymen in an alpaca and a llama,
      detected by vaginal examination and endoscopy, was achieved by use of a
      sigmoidoscope and incremental dilation using cylindrical instruments to a maximum
      diameter of 38 mm. Outcome and subsequent fertility are dependent on length of
      time the obstruction has been present and secondary uterine disease.

PMID- 19183736
TI  - Evaluation of the DG29 test for early detection of pregnancy in cattle.
AB  - The objective of this study was to evaluate a commercial blood test (DG29) for
      pregnancy in cattle. Compared with ultrasound, the sensitivity of the assay for
      detecting pregnancy around day 30 post-insemination was 99.4% [95% confidence
      interval (CI): 96.1-100]. The specificity was 100% (95% CI: 84.7-100) in non
      inseminated cattle, and 66.7%; (95% CI: 49.7-80.4) in inseminated nonpregnant
      cattle. Positive and negative predictive values were 92.6% and 96.3%,
      respectively, in a sample of inseminated cattle in which 80% were pregnant.

PMID- 19183737
TI  - Digital radiography, image archiving and image display: Practical tips.

PMID- 19183738
TI  - 2007 CVMA practice owners economic survey: comparing fees.

PMID- 19183739
TI  - The many challenges of veterinary oncology.

PMID- 19183740
TI  - West Nile virus and hemoparasites in captive snowy owls (Bubo scandiacus)-
      management strategies to optimize survival.
AB  - In August 2005, 2 members of a group of 6 captive snowy owls (Bubo scandiacus) in
      central Saskatchewan died of West Nile virus infection. One of these owls and 3
      of the remaining owls had significant numbers of circulating hemoparasites.
      Management strategies are suggested to reduce morbidity and mortality.

PMID- 19183741
TI  - Diagnostic ophthalmology. Retinal degeneration.

PMID- 19183743
TI  - Excess coronary artery disease risk in South Asian immigrants: can dysfunctional
      high-density lipoprotein explain increased risk?
AB  - BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality and
      morbidity in the United States (US), and South Asian immigrants (SAIs) have a
      higher risk of CAD compared to Caucasians. Traditional risk factors may not
      completely explain high risk, and some of the unknown risk factors need to be
      explored. This short review is mainly focused on the possible role of
      dysfunctional high-density lipoprotein (HDL) in causing CAD and presents an
      overview of available literature on dysfunctional HDL. DISCUSSION: The
      conventional risk factors, insulin resistance parameters, and metabolic syndrome,
      although important in predicting CAD risk, may not sufficiently predict risk in
      SAIs. HDL has antioxidant, antiinflammatory, and antithrombotic properties that
      contribute to its function as an antiatherogenic agent. Recent Caucasian studies
      have shown HDL is not only ineffective as an antioxidant but, paradoxically,
      appears to be prooxidant, and has been found to be associated with CAD. Several
      causes have been hypothesized for HDL to become dysfunctional, including Apo
      lipoprotein A-I (Apo A-I) polymorphisms. New risk factors and markers like
      dysfunctional HDL and genetic polymorphisms may be associated with CAD.
      CONCLUSIONS: More research is required in SAIs to explore associations with CAD
      and to enhance early detection and prevention of CAD in this high risk group.

PMID- 19183742
TI  - Optimizing endothelin receptor antagonist use in the management of pulmonary
      arterial hypertension.
AB  - Endothelin receptor antagonism has emerged as an important therapeutic approach
      in pulmonary arterial hypertension (PAH). Bench to bedside scientific research
      has shown that endothelin-1 (ET-1) is overexpressed in several forms of pulmonary
      vascular disease and may play an important pathogenetic role in the development
      and progression of PAH. Oral endothelin receptor antagonists (ERAs) improved
      exercise capacity, functional status, pulmonary hemodynamics, and delayed the
      time to clinical worsening in several randomized placebo-controlled trials. Two
      ERAs are currently approved by the US Food and Drug Administration: bosentan, a
      dual ERA for patients with class III and IV PAH, and ambrisentan, a selective ERA
      for patients with class II and III PAH. Sitaxsentan, another selective ERA, has
      been approved in Europe, Canada, and Australia. The objective of this review is
      to evaluate the available evidence describing the pharmacology, efficacy, safety,
      and tolerability, and patient-focused perspectives regarding the different types
      of endothelin receptor antagonists. Ongoing and forthcoming randomized trials are
      also highlighted including the approach of combining this class of drugs with
      other drugs that target different cellular pathways believed to be etiologically
      important in PAH.

PMID- 19183744
TI  - Habitual coffee consumption and blood pressure: an epidemiological perspective.
AB  - This paper summarizes the current epidemiological evidence on coffee consumption
      in relation to blood pressure (BP) and risk of hypertension. Data from cross
      sectional studies suggest an inverse linear or U-shaped association of habitual
      coffee use with BP in different populations. Prospective studies suggest a
      protective effect of high coffee intake (4 or more cups per day) against
      hypertension, mainly in women. Furthermore, the risk of hypertension may be lower
      in coffee abstainers. Randomized controlled trials, which are mostly of short
      duration (1-12 weeks), have shown that coffee intake around 5 cups per day causes
      a small elevation in BP (approximately 2/1 mmHg) when compared to abstinence or
      use of decaffeinated coffee. With regard to underlying biological mechanisms,
      most research has been devoted to BP-raising effects of caffeine. However, there
      are many other substances in coffee, such as polyphenols, soluble fibre and
      potassium, which could exert a beneficial effect in the cardiovascular system.
      Although the precise nature of the relation between coffee and BP is still
      unclear, most evidence suggests that regular intake of caffeinated coffee does
      not increase the risk of hypertension.

PMID- 19183745
TI  - The renin angiotensin system in the development of cardiovascular disease: role
      of aliskiren in risk reduction.
AB  - An association has been shown between plasma renin activity (PRA) and the risk of
      cardiovascular disease. There is also evidence that angiotensin II exerts
      detrimental effects on progression and instabilization of atherosclerotic plaque.
      The renin-angiotensin system (RAS) can be inhibited through inhibition of
      angiotensin I (Ang I) generation from angiotensinogen by direct renin inhibitors,
      inhibition of angiotensin II (Ang II) generation from angiotensin I by
      angiotensin-converting enzyme inhibitors and finally by direct inhibition of the
      action of Ang II receptor level. Aliskiren, the first direct renin inhibitor to
      reach the market, is a low-molecular-weight, orally active, hydrophilic
      nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration
      increases because the drugs blocks the negative feed-back exerted by Ang II on
      renin synthesis. Because of its long pharmacological half-life, aliskiren is
      suitable for once-daily administration. Its through-to-peak ratio approximates
      98% for the 300 mg/day dose. Because of its mechanism of action, aliskiren might
      offer the additional opportunity to inhibit progression of atherosclerosis at
      tissue level. Hypertension is an approved indication for this drug, which is also
      promising for the treatment of heart failure. The efficacy of this drug in
      reducing major clinical events is being tested in large ongoing clinical trials.

PMID- 19183746
TI  - Clinical use of parnaparin in major and minor orthopedic surgery: a review.
AB  - Patients undergoing arthroplasty or other orthopedic surgery show a high risk of
      venous thromboembolism (VTE), involving mortality, morbidity, and social costs;
      however, the risk for VTE in minor orthopedic surgery should not be
      underestimated and antithrombotic prophylaxis may be required. According to the
      literature, low-molecular-weight heparins (LMWHs) are more effective in
      preventing VTE than unfractionated heparins (UFHs) or vitamin K antagonists, and
      have a lower hemorrhagic risk. By comparing different prophylactic regimens, it
      has been shown that starting the prophylaxis near the time of the operation is
      the most critical point for efficacy, whether or not the first dose is
      administered pre- or post-operatively. Moreover, most thromboembolic
      complications are observed after discharge and, therefore, many clinicians
      advocate continuing prophylaxis for longer times (6-8 weeks) in order to further
      reduce the rate for VTE. The literature on parnaparin, a new LMWH, in VTE
      prophylaxis was reviewed. Parnaparin is equally effective as UFH, but it offers
      the advantages of a once-daily administration and improved tolerability, thus
      allowing the home management of patients with no need for laboratory coagulation
      tests.

PMID- 19183747
TI  - Update on the clinical utility of fenofibrate in mixed dyslipidemias: mechanisms
      of action and rational prescribing.
AB  - Mixed dyslipidemia is a common lipid disorder characterized by the presence of an
      atherogenic lipoprotein phenotype due to abnormalities in various atherogenic and
      anti-atherogenic lipoproteins. Despite the link between the decrease of LDL
      cholesterol by statin treatment and the prevention of cardiovascular disease, a
      high residual risk is observed in statin trials. This residual risk is partly
      explained by lipoprotein abnormalities other than LDL. Fenofibrate exerts a
      favorable effect on the atherogenic lipid profile of mixed dyslipidemia and can
      effectively reduce cardiovascular disease in patients with mixed dyslipidemia.
      Fenofibrate may offer important treatment alternatives as a second-line therapy
      in several circumstances: in combination with a statin for patients with mixed
      dyslipidemias not at goals on statin mono-therapy; in monotherapy for patients
      intolerant or with contraindication to statin therapy; and in combination with
      other drugs (ezetimibe, colesevelam) for patients with mixed dyslipidemias, known
      intolerance, or contraindication to statin and not at goals on fenofibrate
      monotherapy. However, the role of fenofibrate-statin therapy and of other
      therapies involving fenofibrate in cardiovascular risk reduction strategies
      remains to be established.

PMID- 19183748
TI  - Targeting multiple dyslipidemias with fixed combinations--focus on extended
      release niacin and simvastatin.
AB  - Dyslipidemia is a major risk factor in the initiation and progression of
      cardiovascular diseases such as atherosclerosis. Several pharmacological agents
      have been developed over the past 50 years which target various lipid components
      such as low density lipoprotein (LDL) cholesterol, triglyceride, and high density
      lipoprotein (HDL) cholesterol. Similar to other risk factors such as hypertension
      and diabetes mellitus, the management of dyslipidemia can be complicated and may
      require combination therapy for effective treatment. This review discusses the
      biochemical mechanisms of action and clinical uses for simvastatin (the most
      widely available and commercially prescribed statin) and niacin, and the
      combination of these agents in the management and treatment of dyslipidemia.

PMID- 19183749
TI  - Effects of study design and trends for EVAR versus OSR.
AB  - PURPOSE: To investigate if study design factors such as randomization, multi
      center versus single center evidence, institutional surgical volume, and patient
      selection affect the outcomes for endovascular repair (EVAR) versus open surgical
      repair (OSR). Finally, we investigate trends over time in EVAR versus OSR
      outcomes. METHODS: Search strategies for comparative studies were performed
      individually for: OVID's MEDLINE, EMBASE, CINAHL, HAPI, and Evidence Based
      Medicine (EBM) Reviews (including Cochrane DSR, ACP Journal Club, DARE and CCTR),
      limited to 1990 and November 2006. RESULTS: Identified literature: 84 comparative
      studies pertaining to 57,645 patients. These include 4 randomized controlled
      trials (RCTs), plus 2 RCTs with long-term follow-up. The other 78 comparative
      studies were nonrandomized with 75 reporting perioperative outcomes, of which 16
      were multi-center, and 59 single-center studies. Of the single-center studies 31
      were low-volume and 28 were high-volume centers. In addition, 5 studies had all
      patients anatomically eligible for EVAR, and 8 studies included high-risk
      patients only. Finally, 25 long term observational studies reported outcomes up
      to 3 years. OUTCOMES: Lower perioperative mortality and rates of complications
      for EVAR versus OSR varied across study designs and patient populations. EVAR
      adverse outcomes have decreased in recent times. CONCLUSION: EVAR highlights the
      problem of performing meta-analysis when the experience evolves over time.

PMID- 19183750
TI  - Guar gum and similar soluble fibers in the regulation of cholesterol metabolism:
      current understandings and future research priorities.
AB  - The hypocholesterolemic effects associated with soluble fiber consumption are
      clear from animal model and human clinical investigations. Moreover, the
      modulation of whole-body cholesterol metabolism in response to dietary fiber
      consumption, including intestinal cholesterol absorption and fecal sterol and
      bile acid loss, has been the subject of many published reports. However, our
      understanding of how dietary fibers regulate molecular events at the gene/protein
      level and alter cellular cholesterol metabolism is limited. The modern emphasis
      on molecular nutrition and rapid progress in 'high-dimensional' biological
      techniques will permit further explorations of the role of genetic polymorphisms
      in determining the variable interindividual responses to soluble fibers.
      Furthermore, with traditional molecular biology tools and the application of
      'omic' technology, specific insight into how fibers modulate the expression of
      genes and proteins that regulate intestinal cholesterol absorption and alter
      hepatic sterol balance will be gained. Detailed knowledge of the molecular
      mechanisms by which soluble fibers reduce plasma cholesterol concentrations is
      paramount to developing novel fiber-based "cocktails" that target specific
      metabolic pathways to gain maximal cholesterol reductions.

PMID- 19183751
TI  - Current concepts in the management of hepatopulmonary syndrome.
AB  - The hepatopulmonary syndrome is characterized as the triad of liver disease,
      pulmonary gas exchange abnormalities leading to arterial deoxygenation and
      evidence of intrapulmonary vascular dilatations. This review summarizes the
      pathological mechanisms leading to pulmonary vascular changes in hepatopulmonary
      syndrome. The role of the three currently used diagnostic imaging modalities of
      contrast-enhanced echocardiography, perfusion lung scanning and pulmonary
      arteriography that identify the presence of intrapulmonary vascular abnormalities
      are reviewed. Liver transplantation is considered to be the definitive treatment
      of hepatopulmonary syndrome with often successful reversal of hypoxemia, however
      other treatments have been trialed. This review further appraises the evidence
      for the use of pharmacological agents and the role of radiological interventions
      in hepatopulmonary syndrome.

PMID- 19183752
TI  - Arterial pulmonary hypertension in noncardiac intensive care unit.
AB  - Pulmonary artery pressure elevation complicates the course of many complex
      disorders treated in a noncardiac intensive care unit. Acute pulmonary
      hypertension, however, remains underdiagnosed and its treatment frequently begins
      only after serious complications have developed. Significant pathophysiologic
      differences between acute and chronic pulmonary hypertension make current
      classification and treatment recommendations for chronic pulmonary hypertension
      barely applicable to acute pulmonary hypertension. In order to clarify the
      terminology of acute pulmonary hypertension and distinguish it from chronic
      pulmonary hypertension, we provide a classification of acute pulmonary
      hypertension according to underlying pathophysiologic mechanisms, clinical
      features, natural history, and response to treatment. Based on available data,
      therapy of acute arterial pulmonary hypertension should generally be aimed at
      acutely relieving right ventricular (RV) pressure overload and preventing RV
      dysfunction. Cases of severe acute pulmonary hypertension complicated by RV
      failure and systemic arterial hypotension are real clinical challenges requiring
      tight hemodynamic monitoring and aggressive treatment including combinations of
      pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors.
      The choice of vasopressor and inotropes in patients with acute pulmonary
      hypertension should take into consideration their effects on vascular resistance
      and cardiac output when used alone or in combinations with other agents, and must
      be individualized based on patient response.

PMID- 19183754
TI  - Single photon emission computed tomography: an alternative imaging modality in
      left ventricular evaluation.
AB  - Various diagnostic imaging modalities have been used for quantitative left
      ventricular (LV) parameters. Because of the suboptimal value of the most widely
      used technology, two-dimensional (2D) echocardiography, 3D ultrasonographic
      imaging has improved accuracy for LV volume and function. Single photon emission
      computed tomography (SPECT) is another diagnostic method where LV volumetric and
      functional parameters can be accurately provided by gated myocardial perfusion
      tomographic slices. First pass radionuclide venticulography is another imaging
      modality which has some practical limitations. Despite lower ejection fraction
      (EF) values compared with invasive approach, noninvasive techniques are accurate
      in determination of normal and depressed EF. Noninvasive techniques with 3D
      approach including gated SPECT are beneficial for not only global but also
      regional LV evaluation. It has been mentioned that the slight difference between
      echocardiography and SPECT could be caused by the diverse population studied. The
      results of diagnostic stress tests support that SPECT is feasible to use in
      evaluation of LV volume and functional analysis. Magnetic resonance imaging is an
      expensive modality to use routinely, but it preserves its importance in selected
      patients for providing precise LV geometric data.

PMID- 19183753
TI  - The importance of endothelin-1 for microvascular dysfunction in diabetes.
AB  - Most of the late diabetic complications such as retinopathy, nephropathy, and
      neuropathy, have their basis in disturbed microvascular function. Structural and
      functional changes in the micro-circulation are present in diabetes mellitus
      irrespective of the organ studied, and the pathogenesis is complex. Endothelial
      dysfunction, characterized by an imbalance between endothelium-derived
      vasodilator and vasoconstrictor substances, plays an important role in the
      pathogenesis of diabetic microangiopathy. Increased circulating levels of
      endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been found in patients
      with diabetes, and a positive correlation between plasma ET-1 levels and
      microangiopathy in patients with type 2 diabetes has been demonstrated. In
      addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may
      contribute to endothelial dysfunction through inhibitory effects on nitric oxide
      (NO) production. Vascular endothelial dysfunction may precede insulin resistance,
      although the feature of insulin resistance syndrome includes factors that have
      negative effects on endothelial function. Furthermore, ET-1 induces a reduction
      in insulin sensitivity and may take part in the development of the metabolic
      syndrome. In the following, the mechanisms by which ET-1 contributes to the
      development of diabetic microangiopathy and the potentially beneficial effect of
      selective ET(A) receptor antagonists are discussed.

PMID- 19183755
TI  - ST segment depression in hypertensive patients: a comparison of exercise test
      versus Holter ECG.
AB  - INTRODUCTION: This study compared ST segment depression (ST depression) during
      cycle ergometry (ergometry) versus simultaneous 24-hour ambulatory blood pressure
      measurement and electrocardiogram recording (24-h ABPM/ECG) during everyday life.
      METHODS: In a German multicenter study, ergometry and 24-h ABPM/ECG records of
      239 hypertensive patients were retrospectively analyzed. ST depression was
      defined as an ST segment depression (1 mm limb or chest recordings V1 to V6) in
      an incremental cycle ergometry, or 1 mm in the 24-h ABPM/ECG recording under
      everyday conditions. Blood pressure parameters at the onset of ST depression in
      the context of the respective method were compared. RESULTS: 18 patients had ST
      depression only in ergometry (group B), 23 had ST depression only during 24-h
      ABPM/ECG monitoring (group C) and 28 patients had ST depression with both methods
      (group D). Group A had no ST depression with any method. In group D, at the onset
      of ST depression with 24-h ABPM/ECG investigation, all parameters except
      diastolic blood pressure were significantly lower compared with the corresponding
      parameters at the onset of ST depression with ergometry (systolic blood pressure:
      148 +/- 19 vers 188 +/- 35 mmHg, p < 0.001; heart rate: 93 +/- 12 vs 120 +/- 21
      beat/min, p < 0.0001; double product: 13,714 +/- 2315 vs 22,992 +/- 3,985
      mmHg/min), p < 0.0001). CONCLUSION: ST depressions during everyday life detected
      by 24-h ABPM/ECG are characterized by a substantially lower triggering threshold
      for blood pressure level parameters compared with ergometry. The two methods
      detecting ischemia do not replace but complement each other.

PMID- 19183756
TI  - Postpartum thromboembolism: severe events might be preventable using a new risk
      score model.
AB  - BACKGROUND: Pregnancy-related venous thromboembolism (VTE) is a major cause of
      maternal morbidity and mortality. A new risk assessment model for VTE in relation
      to pregnancy has been introduced in Sweden. We wished to determine the proportion
      of preventable VTE cases if the model had been in use and make a brief cost
      benefit analysis. METHODS: A hospital-based retrospective case-control study of
      all postpartum thromboembolic instances of deep venous thrombosis and pulmonary
      embolisms during a 16-year period. Large anamnestic risk factors at the time of
      delivery were assessed. We correlated the findings with the new Swedish
      guidelines for thromboprophylaxis. RESULTS: We found 37 cases of postpartum VTE
      during the study period. Nineteen of all VTE cases (51%) and eight out of eleven
      of cases of pulmonary embolism (73%) had two or more large anamnestic risk
      factors, ie, they would have been subjected to thromboprophylaxis if the new
      guidelines had been used. The cost of each preventable VTE was lower than
      treating a VTE. CONCLUSION: Approximately one-half of postpartum VTE cases and
      70% of pulmonary emboli cases have at least two large risk factors and might be
      preventable using the new algorithm. From the perspective of the health care
      system the new recommendations appears to be cost-effective.

PMID- 19183757
TI  - Frequency of secondary dyslipidemia in obese children.
AB  - OBJECTIVE: This paper reports the frequency, type, and degree of dyslipidemia in
      obese children before therapeutic intervention. The relationships between lipid
      values and weight status, as well as lipid values and physical fitness, of these
      children were also investigated. DESIGN AND METHODS: The initial examination of
      the Freiburg Intervention Trial for Obese Children (FITOC) measured the values of
      triglycerides (TG), total cholesterol (C), low-density lipoprotein cholesterol
      (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in 546 obese children
      aged 7-12 (body mass index [BMI] > 97th percentile), and compared these values
      with those of the age- and sex-specific reference group in the Lipid Research
      Clinics Population Studies Data Book (LRC). Four groups were selected according
      to the following scheme: A, Normolipidemia; B, Hyper-LDL-cholesterolemia alone;
      C, Hypo-HDL-C + hypertriglyceridemia; D, Combined hyperlipidemia = Hyper-LDL-C +
      hypertriglyceridemia. Body mass index, BMI-SDS (corrected BMI), and physical
      performance in watt/kg body weight were measured. RESULTS: A total of 45.8% of
      the overweight children showed an abnormal lipid profile. Ten percent of the
      children had high LDL-C levels (group B), while 15% had increased LDL-C and
      increased TG (group D) (higher prevalence in boys). In 18.9% we found increased
      TG, combined with decreased HDL-C values (group C). CONCLUSION: Obese children
      are at risk of dyslipoproteinemia and related diseases. Children with the highest
      BMI-SDS and lowest physical fitness have the lowest HDL-C values and increased
      TG, indicating a higher risk for the metabolic syndrome.

PMID- 19183758
TI  - The development of abdominal aortic aneurysms in mice is enhanced by
      benzo(a)pyrene.
AB  - Cigarette smoking has been strongly associated with abdominal aortic aneurysm
      (AAA), but the components of tobacco smoke involved in AAA have not been
      identified. Benzo(a)pyrene (BaP) is an important constituent in cigarette smoke
      capable of induction of alterations strikingly similar to the pathological
      changes seen during AAA development. We therefore hypothesized that BaP exposure
      contributes to the development of AAA. In this study, C57/B6J mice were treated
      with vehicle, angiotensin II (AngII) (0.72 mg/kg/day), BaP (10 mg/kg/week), or
      the combination of AngII and BaP, for 5 weeks, and then examined for incidence of
      AAA and pathological changes of the aortic wall. Results showed that incidence of
      AAA formation in C57/B6J mice treated with BaP and AngII was significantly higher
      than that in AngII-treated mice (7 of 12 compared to 2 of 12). Further, five mice
      in the group treated with AngII/BaP and one in the group treated with AngII
      exhibited AAA rupture and hematoma. BaP caused macrophage infiltration, disarray
      of elastic lamella, and loss of vascular smooth muscle cells (VSMCs). We conclude
      that BaP aggravates AAA formation and rupture in C57/B6J mice by promoting
      macrophage infiltration, degeneration of elastic lamella, and loss of VSMCs in
      the aortic wall.

PMID- 19183759
TI  - Compliance of the aorta in two diseases affecting vascular elasticity, familial
      hypercholesterolemia and diabetes: a MRI study.
AB  - Arterial elasticity changes in familial hypercholesterolemia (FH) and diabetes
      mellitus (DM) with different but overlapping mechanisms. We compared aortic
      elasticity between 19 FH patients with the same mutation, 18 type 2 DM patients,
      and 30 controls, all aged 48 to 64. They underwent aortic magnetic resonance
      imaging, risk-factor assessment, and carotid and femoral ultrasound measurements.
      All patients were on adequate cardiovascular medication including statins and had
      established coronary heart disease (CHD). FH patients had longer-duration CHD
      (13.3 +/- 7.7 years) than did DM patients (5.0 +/- 3.1). Aortic compliance in the
      descending thoracic (DM 0.38 +/- 0.14 vs control 0.53 +/- 0.19, P = 0.032) and
      abdominal aorta (DM 0.45 +/- 0.20 vs control 0.66 +/- 0.25, P = 0.011) was lower
      in DM patients than in controls, whereas no significant difference existed
      between FH patients and controls. Carotid and femoral intima-media thickness was
      greater in FH and DM patients than in controls with no difference between patient
      groups. Carotid or femoral plaques appeared in 15 (79%) FH and in 10 (56%) DM
      patients. One control had a femoral plaque. Five FH patients showed stenosis,
      occlusion or both in carotid arteries. In our opinion, DM patients' lower
      compliance reflect mainly arterial media affecting arteriosclerosis, while FH
      patients' plaque status and longer duration of CHD suggest more advanced
      atherosclerosis. The FH patients may therefore be at increased risk for
      atherothrombotic events. However, due to small patient material, larger
      confirmatory studies are needed.

PMID- 19183760
TI  - Clinical deterioration after sildenafil cessation in patients with pulmonary
      hypertension.
AB  - Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE-5). Its
      chronic administration has been shown to improve exercise capacity, World Health
      Organization functional class, and haemodynamics in patients with symptomatic
      pulmonary arterial hypertension (PAH). There is however, no data describing the
      clinical consequences of sudden cessation of sildenafil treatment. In this
      series, 9 patients with NYHA Class II-IV PAH who were stable on 2 months of
      sildenafil monotherapy, had their sildenafil ceased to accommodate a 2-week
      washout period, required for enrollment in research involving an endothelin
      receptor antagonist. Six minute walk distance (SMWD) and clinical assessments
      were performed before cessation of sildenafil, and again 2 weeks later. Over the
      course of this 2-week washout period, 6 of the 9 patients reported increased
      breathlessness and fatigue, 1 of these was hospitalized with worsening right
      heart failure. The SMWD fell in 6 patients, with falls of greater than 100 m
      recorded in 4 patients. This was accompanied by a worsening of NYHA Class from
      2.5 +/- 0.2 to 3.1 +/- 0.1 (mean +/- SEM, p = 0.01). These data indicate that
      sudden cessation of sildenafil monotherapy, in patients with PAH, carries with it
      a significant and unpredictable risk of rapid clinical deterioration. We
      recommend that if sildenafil needs to be ceased, it would be more prudent to
      consider concurrent vasodilator therapy before the gradual cessation of
      sildenafil.

PMID- 19183761
TI  - Under- and overreporting of energy in a group of candidates for CABG surgery and
      its association with some anthropometric and sociodemographic factors, Tehran,
      Iran.
AB  - INTRODUCTION: Numerous studies have documented a high prevalence of misreporting
      energy intakes. This paper examines the prevalence of under- and overreporting of
      energy intake in a group of candidates for coronary artery bypass graft (CABG)
      surgery and its association with body mass index (BMI) and some sociodemographic
      factors. SUBJECTS AND METHODS: Dietary assessment (using a food frequency
      questionnaire) and demographic evaluation of 449 CABG surgery candidates was
      performed. Weight and height was also measured. McCrory equation was used to
      identify inaccurate records of energy intake. With this equation, reporting
      energy intake less than 78% and more than 122% of predicted energy expenditure
      was considered as under- and overreporting, respectively. RESULTS: Less than half
      of the participants reported energy intakes within the plausible limits. There
      were more overreporters than underreporters in this sample. The only significant
      association between misreporting and related factors was seen in BMI groups. As
      BMI increased, the number of underreporters increased significantly. Expressed as
      a percentage of total energy, mean carbohydrate intake was significantly lower
      and mean fat and protein intake was significantly higher in underreporters
      compared to overreporters. CONCLUSION: The high prevalence of misreporting
      suggests more research to examine the characteristics of misreporters.
      Calibrating data with these characteristics can help to improve intake estimates.

PMID- 19183762
TI  - Validation of the Oregon Scientific BPU 330 for self-monitoring of blood pressure
      according to the International Protocol.
AB  - OBJECTIVE: Extensive marketing of devices for self-measurement of blood pressure
      has created a need for purchasers to be able to satisfy themselves that such
      devices have been evaluated according to agreed criteria. The Oregon Scientific
      BPU 330 blood pressure monitor is an electronic device for upper arm measurement.
      This study assessed the accuracy of the Oregon Scientific BPU 330 blood pressure
      monitor according to the International Protocol by the Working Group on Blood
      Pressure Monitoring of the European Society of Hypertension for validation of
      blood pressure measuring devices. METHOD: 52 participants over 30 years of age
      were studied in the validation. Nine blood pressure measurements were taken
      alternately with a mercury sphygmomanometer by two observers, and by the
      supervisor, using the BPU 330 device. A total of 33 participants were selected
      for the analysis. The validation was divided into two phases. Phase 1 included 15
      participants. If the device passed phase 1, 18 more participants were included.
      The 99 pairs of measurements were compared according to the International
      Protocol. The device was given a pass/fail recommendation based on its accuracy
      compared with the mercury standard (within 5, 10, and 15 mmHg), as well as the
      number met in the ranges specified by the International Protocol. RESULTS: The
      mean and standard deviation of the difference between the mean of the observers
      and the BPU 330 device were 1.7 +/- 4.7 mmHg and 2.8 +/- 3.9 mmHg for systolic
      blood pressure (SBP) and diastolic blood pressure (DBP), respectively. In phase
      1, the device passed with a total of 33, 43, and 44 SBP readings; 38, 44, and 45
      DBP readings were within 5, 10, and 15 mmHg, respectively. In phase 2.1, 81, 95,
      and 96 for SBP, and 83, 95, and 98 for DBP readings fell within the zones of 5,
      10, and 15 mmHg, respectively. In phase 2.2, the last phase, 28 participants fell
      within the zone of two of the three comparisons, lying within 5 mmHg for SBP and
      29 participants for DBP. No participants fell within the zone of all three of
      their comparisons over 5 mmHg apart for both SBP and DBP. CONCLUSION: The BPU 330
      can be recommended for self-monitoring of blood pressure in the adult population,
      according to the International Protocol.

PMID- 19183763
TI  - Maintenance of improved lipid levels following attendance at a cardiovascular
      risk reduction clinic: a 10-year experience.
AB  - BACKGROUND: Specialty cardiovascular risk reduction clinics (CRRC) increase the
      proportion of patients attaining recommended lipid targets; however, it is not
      known if the benefits are sustained after discharge. We evaluated the impact of a
      CRRC on lipid levels and assessed the long-term effect of a CRRC in maintaining
      improved lipid levels following discharge. METHODS: The medical records of
      consecutive dyslipidemic patients discharged > 6 months from a tertiary hospital
      CRRC from January 1991 to January 2001 were retrospectively reviewed. The primary
      outcome was the change in patients' lipid levels between the final CRRC visit and
      the most recent primary care follow-up. A worst-case analysis was conducted to
      evaluate the potential impact of the patients in whom the follow-up lipid
      profiles post-discharge from the CRRC were not obtained. RESULTS: Within the CRRC
      (median follow-up = 1.28 years in 1064 patients), we observed statistically
      significant improvements in all lipid parameters. In the 411 patients for whom
      post-discharge lipid profiles were available (median follow-up = 2.41 years),
      there were no significant differences observed in low-density lipoprotein
      cholesterol, total cholesterol (TC), or triglycerides since CRRC discharge;
      however, there were small improvements in high-density lipoprotein-cholesterol
      (HDL-C) and TC:HDL ratio (p < 0.05 for both). The unadjusted worst-case analysis
      (653 patients with no follow-up lipid profiles) demonstrated statistically
      significant worsening of all lipid parameters between CRRC discharge and the most
      recent follow-up. However, when the change in lipid parameters between the
      baseline and the most recent follow-up was assessed in this analysis, the changes
      in all lipid parameters were significantly improved (p < 0.05). CONCLUSIONS: This
      study demonstrates that a CRRC can improve lipid levels and suggests that these
      benefits are sustained once patients are returned to the care of their primary
      physician.

PMID- 19183764
TI  - Severe macular edema induced by pioglitazone in a patient with diabetic
      retinopathy: a case study.
AB  - We report a case of severe diabetic macular edema (DME) that developed after
      pioglitazone was used by a patient with proliferative diabetic retinopathy. A 30
      year-old woman with poorly controlled type 2 diabetes mellitus visited our clinic
      in 2004. She had moderate pre-proliferative diabetic retinopathy OU. Because of
      the rapid progression of the diabetic retinopathy, she received pan-retinal
      photocoagulation in both eyes. Two weeks before using pioglitazone, her visual
      acuity was 0.9 OD and 0.7 OS. On October 2007, pioglitazone was prescribed by her
      internist because of poorly controlled blood glucose level. Two weeks later, her
      body weight increased, and her face became edematous. Her visual acuity decreased
      to 0.5 OU, and ophthlamoscopy showed severe DME in both eyes. Two weeks after
      stopping pioglitazone, her visual acuity improved to 0.8 OD and 0.5 OS, but the
      DME was still severe in the optical coherence tomographic images. Then, one half
      the usual dose (25 mg) of spironolactone, a diuretic, was given and her macular
      edema was resolved. Her final visual acuity improved to 0.9 OD and 0.7 OS. We
      recommend that when a patient taking pioglitazone complains of decreased vision,
      the physician should promptly consult an ophthalmologist.

PMID- 19183765
TI  - Aberrant positioning of a central venous dialysis catheter to reveal a left-sided
      partial anomalous pulmonary venous connection.
AB  - We describe the identification of a rare, left-sided, partial anomalous pulmonary
      venous connection during routine central venous catheterization. To our
      knowledge, this is the first report in the literature to describe this anomaly in
      a hemodialysis patient. A young man had anomalous connection of the veins
      draining the upper lobe of the left lung and left innominate vein. Our case
      demonstrates the importance of routine fluoroscopy during insertion of central
      venous catheters to detect these anomalies and minimize complications.

PMID- 19183775
TI  - Intrathecal corticosteroids might slow Alzheimer's disease progression.
AB  - Anti-inflammatory drugs for treatment and prevention of Alzheimer's disease have
      to date proved disappointing, including a large study of low-dose prednisone, but
      higher dose steroids significantly reduced amyloid secretion in a small series of
      nondemented patients. In addition, there is a case report of a patient with
      amyloid angiopathy who had complete remission from two doses of dexamethasone,
      and very high dose steroids are already used for systemic amyloidosis. This paper
      presents the hypothesis that pulse-dosed intrathecal methylprednisolone or
      dexamethasone will produce detectable slowing of Alzheimer's progression,
      additive to that obtained with cholinesterase inhibitors and memantine. A
      protocol based on treatment regimens for multiple sclerosis and central nervous
      system lupus is outlined, to serve as a basis for formulating clinical trials.
      Ultimately intrathecal corticosteroids might become part of a multi-agent regimen
      for Alzheimer's disease and also have application for other neurodegenerative
      disorders.

PMID- 19183776
TI  - Potential cellular and regenerative approaches for the treatment of Parkinson's
      disease.
AB  - Parkinson's disease is most commonly treated with a range of
      pharmacotherapeutics, with the more recent introduction of surgical techniques
      including deep-brain stimulation. These have limited capabilities to improve
      symptoms of the disease in more advanced stages, thus new therapeutic strategies
      including the use of viral vectors and stem cells are in development. Providing a
      continuous supply of dopamine to the striatum in an attempt to improve the
      treatment of motor symptoms using enzymes in the dopamine synthesis and machinery
      is one approach. Alternatively, there are tools which may serve to both protect
      and encourage outgrowth of surviving neurons using growth factors or to directly
      replace lost innervation by transplantation of primary tissue or stem cell
      derived dopaminergic neurons. We summarize some of the potential therapeutic
      approaches and also consider the recent EU directives on practical aspects of
      handling viral vectors, cells and tissues, and in the running of clinical trials
      in Europe which impact on their development.

PMID- 19183777
TI  - Cannabinoids in the management of spasticity associated with multiple sclerosis.
AB  - The endocannabinoid system and cannabinoid-based treatments have been involved in
      a wide number of diseases. In particular, several studies suggest that
      cannabinoids and endocannabinoids may have a key role in the pathogenesis and
      therapy of multiple sclerosis (MS). In this study we highlight the main findings
      reported in literature about the relevance of cannabinoid drugs in the management
      and treatment of MS. An increasing body of evidence suggests that cannabinoids
      have beneficial effects on the symptoms of MS, including spasticity and pain. In
      this report we focus on the effects of cannabinoids in the relief of spasticity
      describing the main findings in vivo, in the mouse experimental allergic
      encephalomyelitis model of MS. We report on the current treatments used to
      control MS symptoms and the most recent clinical studies based on cannabinoid
      treatments, although long-term studies are required to establish whether
      cannabinoids may have a role beyond symptom amelioration in MS.

PMID- 19183778
TI  - Brain ischemia and ischemic blood-brain barrier as etiological factors in
      sporadic Alzheimer's disease.
AB  - The development of neuronal death and amyloid plaques is a characteristic feature
      of ischemic- and Alzheimer-type dementia. An important aspect of neuronal loss
      and amyloid plaques are their topography and neuropathogenesis. This review was
      performed to present the hypothesis that different fragments of blood-borne
      amyloid precursor protein are able to enter the ischemic blood-brain barrier.
      Chronic disruption of the blood-brain barrier after ischemic injury was shown. As
      an effect of chronic ischemic blood-brain barrier injury, a visible connection of
      amyloid plaques with neurovasculature was observed. This neuropathology appears
      to have similar distribution and mechanisms to Alzheimer's disease. The
      usefulness of rival ischemic theory in elucidating the neuropathogenesis of
      amyloid plaques formation and neuronal death in Alzheimer's disorder is
      discussed.

PMID- 19183779
TI  - Inflammation as a potential mediator for the association between periodontal
      disease and Alzheimer's disease.
AB  - Periodontal disease (PDD) is associated with increased risk of cardiovascular
      disease, cerebrovascular disease, and mortality in many studies, while other
      studies have begun to suggest an association of PDD with Alzheimer's disease
      (AD). This paper discusses how infectious pathogens and systemic infection may
      play a role in AD. The roles of infection and inflammation are addressed
      specifically with regard to known AD pathologic lesions including senile plaques,
      neuron death, neurofibrillary tangles, and cerebrovascular changes. A testable
      model of proposed pathways between periodontal infection and AD is presented
      including three possible mechanisms: a) direct effects of infectious pathogens,
      b) inflammatory response to pathogens, and c) the effects on vascular integrity.
      The role of gene polymorphisms is discussed, including apolipoprotein (APOE)
      varepsilon4 as a pro-inflammatory and pro-infection genotype.

PMID- 19183782
TI  - Risperidone long-acting injection: a review of its long term safety and efficacy.
AB  - A long-acting form of the second-generation antipsychotic drug risperidone is now
      broadly available for the treatment of schizophrenia and closely related
      psychiatric conditions. It combines the advantage of previously available depot
      formulations for first-generation drugs with the favorable characteristics of the
      modern "atypical" antipsychotics, namely higher efficacy in the treatment of the
      negative symptoms of schizophrenia and reduced motor disturbances. Published
      clinical studies show an objective clinical efficacy (as per psychiatric symptom
      scores and relapse data) that exceeds that of oral atypical antipsychotics when
      patients are switched to the long-acting injectable form, a low incidence of
      treatment-emergent extrapyramidal side effects, and very good acceptance by
      patients. Available data for maintenance treatment of bipolar disorder show
      equivalence with the oral form instead of superiority, but are still limited. As
      it seems likely that efficacy benefits are mostly due to the fact that the
      injectable form reduces the demand for patient compliance to one physician visit
      every 2 weeks instead of self-administration on a daily or twice-daily basis,
      additional potential could exist in other psychiatric disorders where atypical
      antipsychotic drugs are of benefit but where patient adherence to treatment
      schedules is typically low.

PMID- 19183780
TI  - Traumatic brain injury: future assessment tools and treatment prospects.
AB  - Traumatic brain injury (TBI) is widespread and leads to death and disability in
      millions of individuals around the world each year. Overall incidence and
      prevalence of TBI are likely to increase in absolute terms in the future.
      Tackling the problem of treating TBI successfully will require improvements in
      the understanding of normal cerebral anatomy, physiology, and function throughout
      the lifespan, as well as the pathological and recuperative responses that result
      from trauma. New treatment approaches and combinations will need to be targeted
      to the heterogeneous needs of TBI populations. This article explores and
      evaluates the research evidence in areas that will likely lead to a reduction in
      TBI-related morbidity and improved outcomes. These include emerging assessment
      instruments and techniques in areas of structural/chemical and functional
      neuroimaging and neuropsychology, advances in the realms of cell-based therapies
      and genetics, promising cognitive rehabilitation techniques including cognitive
      remediation and the use of electronic technologies including assistive devices
      and virtual reality, and the emerging field of complementary and alternative
      medicine.

PMID- 19183781
TI  - Attention-deficit-hyperactivity disorder and reward deficiency syndrome.
AB  - Molecular genetic studies have identified several genes that may mediate
      susceptibility to attention deficit hyperactivity disorder (ADHD). A consensus of
      the literature suggests that when there is a dysfunction in the "brain reward
      cascade," especially in the dopamine system, causing a low or hypo-dopaminergic
      trait, the brain may require dopamine for individuals to avoid unpleasant
      feelings. This high-risk genetic trait leads to multiple drug-seeking behaviors,
      because the drugs activate release of dopamine, which can diminish abnormal
      cravings. Moreover, this genetic trait is due in part to a form of a gene (DRD(2)
      A1 allele) that prevents the expression of the normal laying down of dopamine
      receptors in brain reward sites. This gene, and others involved in
      neurophysiological processing of specific neurotransmitters, have been associated
      with deficient functions and predispose individuals to have a high risk for
      addictive, impulsive, and compulsive behavioral propensities. It has been
      proposed that genetic variants of dopaminergic genes and other "reward genes" are
      important common determinants of reward deficiency syndrome (RDS), which we
      hypothesize includes ADHD as a behavioral subtype. We further hypothesize that
      early diagnosis through genetic polymorphic identification in combination with
      DNA-based customized nutraceutical administration to young children may attenuate
      behavioral symptoms associated with ADHD. Moreover, it is concluded that dopamine
      and serotonin releasers might be useful therapeutic adjuncts for the treatment of
      other RDS behavioral subtypes, including addictions.

PMID- 19183783
TI  - The role of duloxetine in the treatment of anxiety disorders.
AB  - Anxiety disorders (ADs) are the most common type of psychiatric disorders, with a
      mean incidence of 18.1% and a lifetime prevalence of 28.8%. Pharmacologic options
      studied for treating ADs may include benzodiazepines, tricyclic antidepressants
      (TCA), selective serotonin reuptake inhibitors (SSRIs), noradrenergic and
      specific serotonergic drug (NaSSA) and dual-reuptake inhibitors of serotonin and
      norepinephrine (SNRIs). In this context, the development of SNRIs (venlafaxine
      and duloxetine) has been particularly useful. As a dual-acting intervention that
      targets two neurotransmitter systems, these medications would appePar promising
      for the treatment of ADs. The purpose of this review was to elucidate current
      facts and views about the role of duloxetine in the treatment of ADs. In February
      2007, duloxetine was approved by FDA for the treatment of generalized anxiety
      disorder (GAD). The results of trials evaluating the use duloxetine in the
      treatment of GAD are supportive on its efficacy even if further studies on long
      term use are needed. Apart from some interesting case reports, no large studies
      are, to date, present in literature about duloxetine and other ADs such as panic
      disorder, social anxiety disorder, obsessive-compulsive disorder and post
      traumatic stress disorder. Therefore, the clinical efficacy and the relative good
      tolerability of duloxetine may be further investigated to widen the therapeutic
      spectrum of ADs.

PMID- 19183785
TI  - Direct and indirect effects of paliperidone extended-release tablets on negative
      symptoms of schizophrenia.
AB  - Direct and indirect effects of the new psychotropic paliperidone extended-release
      (paliperidone ER) tablets on negative symptom improvement in schizophrenia were
      investigated using path analysis. A post hoc analysis of pooled data from three 6
      week, double-blind, placebo-controlled studies of paliperidone ER in patients
      experiencing acute exacerbation was conducted. Regression analysis explored
      relationships between baseline/study characteristics and negative symptoms.
      Change in Positive and Negative Syndrome Scale (PANSS) negative factor score at
      endpoint was the dependent variable; explanatory variables included demographic
      and clinical characteristics. Path analysis determined direct and indirect
      effects of treatment on negative symptom change. Indirect mediators of negative
      symptom change in the model included changes in positive symptoms,
      anxiety/depression symptoms and movement disorders. Path analysis indicated that
      up to 33% of negative symptom improvement was a direct treatment effect. Indirect
      effects on negative symptoms were mediated through changes in positive symptoms
      (51%) and anxiety/depression symptoms (18%), whereas changes in movement
      disorders had a 2.1% inverse effect. Path analysis indicated that paliperidone ER
      has a direct effect on negative symptoms. Negative symptom improvement also was
      indirectly mediated via changes in positive and depressive symptoms.

PMID- 19183784
TI  - Augmentation treatment in major depressive disorder: focus on aripiprazole.
AB  - Major depressive disorder (MDD) is a disabling psychiatric condition for which
      effective treatment remains an outstanding need. Antidepressants are currently
      the mainstay of treatment for depression; however, almost two-thirds of patients
      will fail to achieve remission with initial treatment. As a result, a range of
      augmentation and combination strategies have been used in order to improve
      outcomes for patients. Despite the popularity of these approaches, limited data
      from double-blind, randomized, placebo-controlled studies are available to allow
      clinicians to determine which are the most effective augmentation options or
      which patients are most likely to respond to which options. Recently, evidence
      has shown that adjunctive therapy with atypical antipsychotics has the potential
      for beneficial antidepressant effects in the absence of psychotic symptoms. In
      particular, aripiprazole has shown efficacy as an augmentation option with
      standard antidepressant therapy in two, large, randomized, double-blind studies.
      Based on these efficacy and safety data, aripiprazole was recently approved by
      the FDA as adjunctive therapy for MDD. The availability of this new treatment
      option should allow more patients with MDD to achieve remission and, ultimately,
      long-term, successful outcomes.

PMID- 19183786
TI  - Five personality dimensions in patients with irritable bowel syndrome.
AB  - AIM: Irritable bowel syndrome (IBS) as a functional disorder of the
      gastrointestinal tract has been related to psychological factors. Aim of this
      study is to study the differences of personality factors between IBS patients
      compared to our general population. METHODS: This study was performed in clinics
      of Tabriz Medical University during 2006-2007. IBS was diagnosed using the Rome
      II diagnostic criteria after exclusion of organic bowel pathology. The entry of
      each patient was confirmed following a psychiatric interview and after any
      comorbid psychiatry disorder was ruled out. Personality traits and score of each
      factor was evaluated using NEO five factor personality inventory compared to
      results of a previous study on general population of Iran. RESULTS: One hundred
      and sixty six patients were studied. The mean age (+/-SD) of them was 33.6(+/
      11.4) years (60.8% female). Our study population had their symptoms for a mean
      interval of 47.3 month. The bowel problems were provoked by distress in more than
      80% of patients. Pain in female patients was reported to be more frequent but
      both gender described the association between stressors and their symptoms. NEO
      Five-Factor Inventory showed a significantly higher level of neuroticism and
      conscientiousness and lower level of openness and agreeableness in theses
      nonpsychiatric IBS patients. Women with IBS had significantly higher levels of
      openness, conscientiousness, and extraversion compared to men. CONCLUSION:
      Differences were observed between IBS patients and general population. Patients
      with IBS may benefit from psychological interventions.

PMID- 19183787
TI  - The efficacy of mirtazapine in agitated patients with Alzheimer's disease: A 12
      week open-label pilot study.
AB  - Agitation is one of the most devastating behavioral symptoms in demented patients
      but there is little evidence about effective and safe pharmacotherapy. We aimed
      to determine the effectiveness and safety of mirtazapine in treatment of agitated
      patients with Alzheimer's disease (AD). The consecutive patients with AD who have
      significant agitation were assigned to a 12-week open-label, prospective study.
      Patients received mirtazapine 15-30 mg/day. The changes in Cohen-Mansfield
      Agitation Inventory-Short form (CMAI-SF) scores were primary outcome measurement.
      The change in Clinical Global Impression-Severity scale (CGI-S) scores and
      tolerability-safety profile were the secondary efficacy variables. Thirteen of 16
      (81.25%) patients completed the study. There was a significant reduction in CMAI
      SF and CGI-S between the pre- and post-treatment with mirtzapaine (p < 0.001).
      The mean baseline score was 26.54 ( +/- 5.4) and mean reduction was 10.6 ( +/-
      7.5) in CMAI-SF. There was no significant side effect and cognitive
      deterioration. The results of this open-label pilot study suggest that
      mirtazapine may be an effective choice for treatment of agitated patients with
      AD.

PMID- 19183788
TI  - An economic evaluation of aripiprazole vs olanzapine adapted to the Italian
      setting using outcomes of metabolic syndrome and risk for diabetes in patients
      with schizophrenia.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of aripiprazole and olanzapine in
      patients with schizophrenia. METHODS: Data from a double-blind, randomized study
      demonstrating the efficacy of aripiprazole and olanzapine were used to observe
      new incidence of metabolic syndrome (26-week therapy) and to model the risk of
      developing diabetes over 5 years of therapy. Cumulative incidence of metabolic
      syndrome was compared using Kaplan-Meier estimates; diabetes risk was estimated
      using a validated, general population risk-prediction model. Economic assessment
      was conducted from the third-party payer perspective by evaluating
      pharmacotherapy costs of treating schizophrenia and medical costs associated with
      treating adverse metabolic effects in a hypothetical cohort of 1000 patients.
      Resource utilization and costs were derived from the underlying study and
      published data, using a 3% rate to discount costs and benefits. RESULTS: For the
      patients switched from olanzapine to aripiprazole, treatment with aripiprazole
      was a dominant cost-saving strategy. Use of aripiprazole avoided 184 events of
      metabolic syndrome over 26 weeks of treatment, contributing to a real-world (RW)
      cost savings of euro2.53 per patient and a total savings of approximately
      euro465.52 over a 5-year period. For the same cohort, the risk-prediction model
      indicated that 34 occurrences of diabetes could be avoided over 5 years,
      corresponding to a RW cost savings of euro56.86 per patient and a total saving of
      approximately euro1,933.24. These savings reflect avoided costs in treating
      adverse metabolic events and comparable costs in the acquisition of aripiprazole.
      CONCLUSIONS: Maintenance aripiprazole therapy offers medical and economic
      benefits over olanzapine, reflected by reduced incidence of metabolic syndrome
      and diabetes and associated lower costs.

PMID- 19183789
TI  - Validity and reliability of the Structured Clinical Interview for
      Depersonalization-Derealization Spectrum (SCI-DER).
AB  - This study evaluates the validity and reliability of a new instrument developed
      to assess symptoms of depresonalization: the Structured Clinical Interview for
      the Depersonalization-Derealization Spectrum (SCI-DER). The instrument is based
      on a spectrum model that emphasizes soft-signs, sub-threshold syndromes as well
      as clinical and subsyndromal manifestations. Items of the interview include, in
      addition to DSM-IV criteria for depersonalization, a number of features derived
      from clinical experience and from a review of phenomenological descriptions.
      Study participants included 258 consecutive patients with mood and anxiety
      disorders, 16.7% bipolar I disorder, 18.6% bipolar II disorder, 32.9% major
      depression, 22.1% panic disorder, 4.7% obsessive compulsive disorder, and 1.5%
      generalized anxiety disorder; 2.7% patients were also diagnosed with
      depersonalization disorder. A comparison group of 42 unselected controls was
      enrolled at the same site. The SCI-DER showed excellent reliability and good
      concurrent validity with the Dissociative Experiences Scale. It significantly
      discriminated subjects with any diagnosis of mood and anxiety disorders from
      controls and subjects with depersonalization disorder from controls. The
      hypothesized structure of the instrument was confirmed empirically.

PMID- 19183790
TI  - Errorless learning and spaced retrieval techniques to relearn instrumental
      activities of daily living in mild Alzheimer's disease: A case report study.
AB  - Previous studies on cognitive training in Alzheimer's disease (AD) were
      principally aimed at making patients learn items not related to functional needs.
      However, AD patients also experience difficulties with instrumental activities of
      daily living (IADL). The goal of the present multiple baseline case report study
      was to assess the preliminary efficacy and tolerability of an individualized
      cognitive training program using the errorless learning (EL) and spaced-retrieval
      (SR) techniques to relearn forgotten IADLs in mild AD. Following an exhaustive
      neuropsychological assessment, two participants received two training sessions
      per week during four weeks. Participant A was trained to use his voice mail and
      Participant B, to manage the messages from his answering machine. The results
      showed that the program was well tolerated and improved performance on the
      trained tasks. These ameliorations were maintained over a 5-week period. The
      effects of the training did not have any impact on global cognitive functions
      since the results on these measures remained relatively stable. This case report
      demonstrated preliminary efficacy of a new cognitive training program using EL
      and SR techniques tailored to the needs of AD patients. This is an important
      finding since the loss of these capacities alters autonomy in AD patients.

PMID- 19183791
TI  - DNA methylation signature analysis: how easy is it to perform?
AB  - Epigenetic changes, or heritable alterations in gene function that do not affect
      DNA sequence, are rapidly gaining acceptance as co-conspirators in
      carcinogenesis. Although DNA methylation signature analysis by methylation
      specific polymerase chain reaction has been a breakthrough method in speed and
      sensitivity for gene methylation studies, several factors still limit its
      application as a routine diagnostic and prognostic test.

PMID- 19183792
TI  - Optimization of proteomic sample preparation procedures for comprehensive protein
      characterization of pathogenic systems.
AB  - Mass spectrometry-based proteomics is a powerful analytical tool for
      investigating pathogens and their interactions within a host. The sensitivity of
      such analyses provides broad proteome characterization, but the sample-handling
      procedures must first be optimized to ensure compatibility with the technique and
      to maximize the dynamic range of detection. The decision-making process for
      determining optimal growth conditions, preparation methods, sample analysis
      methods, and data analysis techniques in our laboratory is discussed herein with
      consideration of the balance in sensitivity, specificity, and biomass losses
      during analysis of host-pathogen systems.

PMID- 19183793
TI  - Optimization of immobilized gallium (III) ion affinity chromatography for
      selective binding and recovery of phosphopeptides from protein digests.
AB  - Although widely used in proteomics research for the selective enrichment of
      phosphopeptides from protein digests, immobilized metal-ion affinity
      chromatography (IMAC) often suffers from low specificity and differential
      recovery of peptides carrying different numbers of phosphate groups. By
      systematically evaluating and optimizing different loading, washing, and elution
      conditions, we have developed an efficient and highly selective procedure for the
      enrichment of phosphopeptides using a commercially available gallium(III)-IMAC
      column (PhosphoProfile, Sigma). Phosphopeptide enrichment using the reagents
      supplied with the column is incomplete and biased toward the recovery and/or
      detection of smaller, singly phosphorylated peptides. In contrast, elution with
      base (0.4 M ammonium hydroxide) gives efficient and balanced recovery of both
      singly and multiply phosphorylated peptides, while loading peptides in a strong
      acidic solution (1% trifluoracetic acid) further increases selectivity toward
      phosphopeptides, with minimal carryover of nonphosphorylated peptides. 2,5
      Dihydroxybenzoic acid, a matrix commonly used when analyzing phosphopeptides by
      matrix-assisted laser desorption/ionization mass spectrometry was also evaluated
      as an additive in loading and eluting solvents. Elution with 50% acetonitrile
      containing 20 mg/mL dihydroxybenzoic acid and 1% phosphoric acid gave results
      similar to those obtained using ammonium hydroxide as the eluent, although the
      latter showed the highest specificity for phosphorylated peptides.

PMID- 19183794
TI  - Aptamer selection express: a novel method for rapid single-step selection and
      sensing of aptamers.
AB  - Here we describe a new DNA capture element (DCE) sensing system, based on the
      quenching and dequenching of a double-stranded aptamer. This system shows very
      good sensitivity and thermal stability. While quenching, dequenching, and
      separating the DCE systems made from different aptamers (all selected by SELEX),
      an alternative method to rapidly select aptamers was developed-the Aptamer
      Selection Express (ASExp). This process has been used to select aptamers against
      different types of targets (Bacillus anthracis spores, Bacillus thuringiensis
      spores, MS-2 bacteriophage, ovalbumin, and botulinum neurotoxin). The DCE systems
      made from botulinum neurotoxin aptamers selected by ASExp have been investigated.
      The results of this investigation indicate that ASExp can be used to rapidly
      select aptamers for the DCE sensing system.

PMID- 19183795
TI  - Systematic internal standard selection for capillary liquid chromatography-mass
      spectrometry time normalization to facilitate serum proteomics.
AB  - Because blood interacts with almost all tissues of the body, it is likely that
      changes in the overall health of an organism will be reflected in the quantities
      of specific serum peptides and proteins, making them biomarkers. Due to the
      complexity of serum, pre-analytical sample simplification and separation are
      needed prior to mass spectrometric analysis. Use of a reverse-phase capillary
      column coupled to a mass spectrometer allows for separation and analysis of serum
      as part of efforts to discover biomarkers. Even after sample simplification by
      organic solvent precipitation, data files for a single sample typically exceed
      one gigabyte, making it difficult to analyze complete serum mass spectrometry
      profiles with currently available software. However, with adequate safeguards, it
      appears possible to consider portions of mass spectra to find differences in peak
      intensities between clinical comparison groups visually. To facilitate this, the
      elution profile was divided into 2-min intervals in which mass spectrometry data
      were averaged. This required that molecular species had defined reproducible
      elution times. Given liquid chromatography coupled to mass spectrometry
      variation, misalignment of elution times of individual peaks occurred often.
      Hence, internal time controls were identified within each window and used for
      elution time normalization. This significantly reduced variability in data. This
      approach allowed for peak alignment across samples, improving biomarker
      discovery.

PMID- 19183796
TI  - Optimizing electroporation conditions in primary and other difficult-to-transfect
      cells.
AB  - Electroporation is a valuable tool for nucleic acid delivery because it can be
      used for a wide variety of cell types. Many scientists are shifting toward the
      use of cell types that are more relevant to in vivo applications, including
      primary cells, which are considered difficult to transfect. The ability to
      electroporate these cell types with nucleic acid molecules of interest at a
      relatively high efficiency while maintaining cell viability is essential for
      elucidating the pathway(s) in which a gene product is involved. We present data
      demonstrating that by optimizing electroporation parameters, nucleic acid
      molecules can be delivered in a highly efficient manner. We display transfection
      results for primary and difficult-to-transfect cell types including human primary
      fibroblasts, human umbilical vein endothelial cells, Jurkat cells, and two
      neuroblastoma cell lines [SK-N-SH (human) and Neuro-2A (mouse)] with plasmid DNAs
      and siRNAs. Our data demonstrate that by determining proper electroporation
      conditions, glyceraldehyde phosphate dehydrogenase mRNA was silenced in Jurkat
      cells when compared with negative control siRNA electroporations as early as 4 h
      post-transfection. Other experiments demonstrated that optimized electroporation
      conditions using a fluorescently labeled transfection control siRNA resulted in
      75% transfection efficiency for Neuro-2A, 93% for human primary fibroblasts, and
      94% for HUVEC cells, as analyzed by flow cytometry.

PMID- 19183797
TI  - Effect of primer proximity to a difficult-to-sequence region on read length and
      sequence quality.
AB  - Anecdotal and not well-established evidence implies that there could be some
      effect of primer proximity in relation to a difficult region on read length and
      sequence quality. In this paper we sequenced many different categories of
      difficult regions where primers were located at various distances in relation to
      such regions and we found that there is only weak, if any, correlation between
      primer proximity and read length or sequence quality. The occasional improvements
      observed in some studies could be related instead to more optimal primers or
      better quality DNA. We suggest that instead of trying to design primers at
      varying distances to a difficult region, sequence finishers concentrate on
      applying modified chemistries appropriate to a given difficult region.

PMID- 19183798
TI  - Systematic method for determining an ideal housekeeping gene for real-time PCR
      analysis.
AB  - To standardize the amount of biological material between samples (e.g., number of
      cells or amount of tissue) for quantitative real-time reverse transcriptase PCR
      (qRT-PCR), the cycle of the target gene at which expression is detected (the
      cycle threshold, or Ct) is divided by the Ct of a gene either thought to be
      unaffected by experimental conditions or similarly expressed among donors. Genes
      that maintain cellular structure or homeostasis, referred to as housekeeping
      genes, or 18S ribosomal RNA are often used for this purpose. Although unstable or
      inconsistent housekeeping gene expression will misrepresent experimental effects
      on target gene expression, housekeeping genes are often chosen arbitrarily rather
      than systematically. We designed a simple and systematic approach towards
      selection of housekeeping genes based on Ct variance (as reflected by the
      standard deviation) and normality of distribution. We validated this approach by
      comparing stability and consistency of expression of 11 housekeeping genes across
      different types of cells, experimental treatments, and human donors. Finally, we
      demonstrated the consequences of inconsistent housekeeping gene expression on the
      calculation of target gene expression, and conclude that validation of stability
      of housekeeping gene expression by considering both distribution normality and
      standard deviation is straightforward and critical for proper experimental
      design.

PMID- 19183799
TI  - Devitalization of transgenic seed that preserves DNA and protein integrity.
AB  - Agricultural biotechnology companies have been asked to provide intact transgenic
      seed to regulatory agencies as reference materials for evaluating transgene and
      protein detection methods (PCR and immunoassay). Due to intellectual-property and
      product-stewardship considerations, submission of devitalized seed prior to
      regulatory approval is preferable in any given country. Commonly used
      devitalization procedures, such as heating or autoclaving, degrade the protein
      and/or DNA rendering the seed unfit as a reference material for these tests. A
      novel method for devitalizing seed was developed that involves hydration,
      freezing in liquid nitrogen, and lyophilization. The devitalization method
      described here was found to preserve the transgenic DNA and protein in cotton
      (Gossypium hirsutum) and maize (Zea mays) seed allowing its use as a reference
      material for evaluating detection methods.

PMID- 19183800
TI  - Toward sustaining women in careers in core laboratories--a workshop review
      including recommendations from the Association of Biomolecular Resource
      Facilities.
AB  - Review of "From Doctorate to Dean or Director: Sustaining Women Through Critical
      Transition Points in Science, Engineering, and Medicine" (workshop held by the
      Committee on Women in Science, Engineering, and Medicine of the National
      Academies, Washington DC, September 18-19, 2008).

PMID- 19183802
TI  - Diagnostic accuracy of S100B urinary testing at birth in full-term asphyxiated
      newborns to predict neonatal death.
AB  - BACKGROUND: Neonatal death in full-term infants who suffer from perinatal
      asphyxia (PA) is a major subject of investigation, since few tools exist to
      predict patients at risk of ominous outcome. We studied the possibility that
      urine S100B measurement may identify which PA-affected infants are at risk of
      early postnatal death. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study
      between January 1, 2001 and December 1, 2006 we measured S100B protein in urine
      collected from term infants (n = 132), 60 of whom suffered PA. According to their
      outcome at 7 days, infants with PA were subsequently classified either as
      asphyxiated infants complicated by hypoxic ischemic encephalopathy with no
      ominous outcome (HIE Group; n = 48), or as newborns who died within the first
      post-natal week (Ominous Outcome Group; n = 12). Routine laboratory variables,
      cerebral ultrasound, neurological patterns and urine concentrations of S100B
      protein were determined at first urination and after 24, 48 and 96 hours. The
      severity of illness in the first 24 hours after birth was measured using the
      Score for Neonatal Acute Physiology-Perinatal Extension (SNAP-PE). Urine S100B
      levels were higher from the first urination in the ominous outcome group than in
      healthy or HIE Groups (p<0.001 for all), and progressively increased. Multiple
      logistic regression analysis showed a significant correlation between S100B
      concentrations and the occurrence of neonatal death. At a cut-off >1.0 microg/L
      S100B had a sensitivity/specificity of 100% for predicting neonatal death.
      CONCLUSIONS/SIGNIFICANCE: Increased S100B protein urine levels in term newborns
      suffering PA seem to suggest a higher risk of neonatal death for these infants.

PMID- 19183804
TI  - Nitric oxide administration using an oxygen hood: a pilot trial.
AB  - BACKGROUND: We have shown earlier that inhaled nitric oxide (iNO) administered by
      oxygen hood reduces pulmonary hypertension in an animal model (J Perinatol 2002;
      22:50-6). Our objective in this study was to determine feasibility of iNO by
      oxygen hood in neonates with elevated alveolar-arterial oxygen gradients (A
      aDO(2)). METHODS/PRINCIPAL FINDINGS: Masked randomized controlled pilot trial.
      Inclusion criteria were: gestation>or=34 weeks, age<7 days, with post-ductal
      arterial line, and A-aDO(2) 400-600. Infants were randomized to study gas (iNO 20
      ppm or equivalent O(2) flow) for 1 hr which was then weaned over the next 4
      hours. Primary outcome was PaO(2) one hour post-randomization. Four infants each
      were randomized to iNO or O(2) (controls). Two of the four infants given iNO had
      an increase in PaO(2) of >100 torr, while oxygenation was unchanged in the
      controls. Methemoglobinemia and other adverse effects were not noted in any
      infant. Environmental levels of NO and NO(2) were minimal (<1 ppm) at >0.3 m from
      the hood. CONCLUSIONS: Administration of iNO by oxygen hood is feasible. Larger
      randomized controlled trials are required to measure the efficacy and determine
      an appropriate target population for this technique. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00041548.

PMID- 19183803
TI  - Modulation of the beta-catenin signaling pathway by the dishevelled-associated
      protein Hipk1.
AB  - BACKGROUND: Wnts are evolutionarily conserved ligands that signal through beta
      catenin-dependent and beta-catenin-independent pathways to regulate cell fate,
      proliferation, polarity, and movements during vertebrate development. Dishevelled
      (Dsh/Dvl) is a multi-domain scaffold protein required for virtually all known Wnt
      signaling activities, raising interest in the identification and functions of Dsh
      associated proteins. METHODOLOGY: We conducted a yeast-2-hybrid screen using an N
      terminal fragment of Dsh, resulting in isolation of the Xenopus laevis ortholog
      of Hipk1. Interaction between the Dsh and Hipk1 proteins was confirmed by co
      immunoprecipitation assays and mass spectrometry, and further experiments suggest
      that Hipk1 also complexes with the transcription factor Tcf3. Supporting a
      nuclear function during X. laevis development, Myc-tagged Hipk1 localizes
      primarily to the nucleus in animal cap explants, and the endogenous transcript is
      strongly expressed during gastrula and neurula stages. Experimental manipulations
      of Hipk1 levels indicate that Hipk1 can repress Wnt/beta-catenin target gene
      activation, as demonstrated by beta-catenin reporter assays in human embryonic
      kidney cells and by indicators of dorsal specification in X. laevis embryos at
      the late blastula stage. In addition, a subset of Wnt-responsive genes
      subsequently requires Hipk1 for activation in the involuting mesoderm during
      gastrulation. Moreover, either over-expression or knock-down of Hipk1 leads to
      perturbed convergent extension cell movements involved in both gastrulation and
      neural tube closure. CONCLUSIONS: These results suggest that Hipk1 contributes in
      a complex fashion to Dsh-dependent signaling activities during early vertebrate
      development. This includes regulating the transcription of Wnt/beta-catenin
      target genes in the nucleus, possibly in both repressive and activating ways
      under changing developmental contexts. This regulation is required to modulate
      gene expression and cell movements that are essential for gastrulation.

PMID- 19183805
TI  - Zebrafish kidney phagocytes utilize macropinocytosis and Ca+-dependent endocytic
      mechanisms.
AB  - BACKGROUND: The innate immune response constitutes the first line of defense
      against invading pathogens and consists of a variety of immune defense mechanisms
      including active endocytosis by macrophages and granulocytes. Endocytosis can be
      used as a reliable measure of selective and non-selective mechanisms of antigen
      uptake in the early phase of an immune response. Numerous assays have been
      developed to measure this response in a variety of mammalian and fish species.
      The small size of the zebrafish has prevented the large-scale collection of
      monocytes/macrophages and granulocytes for these endocytic assays.
      METHODOLOGY/PRINCIPAL FINDINGS: Pooled zebrafish kidney hematopoietic tissues
      were used as a source of phagocytic cells for flow-cytometry based endocytic
      assays. FITC-Dextran, Lucifer Yellow and FITC-Edwardsiella ictaluri were used to
      evaluate selective and non-selective mechanisms of uptake in zebrafish
      phagocytes. CONCLUSIONS/SIGNIFICANCE: Zebrafish kidney phagocytes characterized
      as monocytes/macrophages, neutrophils and lymphocytes utilize macropinocytosis
      and Ca(2+)-dependant endocytosis mechanisms of antigen uptake. These cells do not
      appear to utilize a mannose receptor. Heat-killed Edwardsiella ictaluri induces
      cytoskeletal interactions for internalization in zebrafish kidney
      monocytes/macrophages and granulocytes. The proposed method is easy to implement
      and should prove especially useful in immunological, toxicological and
      epidemiological research.

PMID- 19183806
TI  - QTL mapping in new Arabidopsis thaliana advanced intercross-recombinant inbred
      lines.
AB  - BACKGROUND: Even when phenotypic differences are large between natural or
      domesticated strains, the underlying genetic basis is often complex, and causal
      genomic regions need to be identified by quantitative trait locus (QTL) mapping.
      Unfortunately, QTL positions typically have large confidence intervals, which
      can, for example, lead to one QTL being masked by another, when two closely
      linked loci are detected as a single QTL. One strategy to increase the power of
      precisely localizing small effect QTL, is the use of an intercross approach
      before inbreeding to produce Advanced Intercross RILs (AI-RILs).
      METHODOLOGY/PRINCIPAL FINDINGS: We present two new AI-RIL populations of
      Arabidopsis thaliana genotyped with an average intermarker distance of 600 kb.
      The advanced intercrossing design led to expansion of the genetic map in the two
      populations, which contain recombination events corresponding to 50 kb/cM in an
      F(2) population. We used the AI-RILs to map QTL for light response and flowering
      time, and to identify segregation distortion in one of the AI-RIL populations due
      to a negative epistatic interaction between two genomic regions.
      CONCLUSIONS/SIGNIFICANCE: The two new AI-RIL populations, EstC and KendC, derived
      from crosses of Columbia (Col) to Estland (Est-1) and Kendallville (Kend-L)
      provide an excellent resource for high precision QTL mapping. Moreover, because
      they have been genotyped with over 100 common markers, they are also excellent
      material for comparative QTL mapping.

PMID- 19183807
TI  - Hepatitis C virus is a weak inducer of interferon alpha in plasmacytoid dendritic
      cells in comparison with influenza and human herpesvirus type-1.
AB  - Plasmacytoid dendritic cells (pDCs) are responsible for the production of type I
      IFN during viral infection. Viral elimination by IFN-alpha-based therapy in more
      than 50% of patients chronically infected with hepatitis C virus (HCV) suggests a
      possible impairment of production of endogenous IFN-alpha by pDCs in infected
      individuals. In this study, we investigated the impact of HCV on pDC function. We
      show that exposure of pDCs to patient serum- and cell culture-derived HCV
      resulted in production of IFN-alpha by pDCs isolated from some donors, although
      this production was significantly lower than that induced by influenza and human
      herpesvirus type 1 (HHV-1). Using specific inhibitors we demonstrate that
      endocytosis and endosomal acidification were required for IFN-alpha production by
      pDCs in response to cell culture-derived HCV. HCV and noninfectious HCV-like
      particles inhibited pDC-associated production of IFN-alpha stimulated with Toll
      like receptor 9 (TLR9) agonists (CpG-A or HHV-1) but not that of IFN-alpha
      stimulated with TLR7 agonists (resiquimod or influenza virus). The blockade of
      TLR9-mediated production of IFN-alpha, effective only when pDCs were exposed to
      virus prior to or shortly after CpG-A stimulation, was already detectable at the
      IFN-alpha transcription level 2 h after stimulation with CpG-A and correlated
      with down-regulation of the transcription factor IRF7 expression and of TLR9
      expression. In conclusion, rapidly and early occurring particle-host cell protein
      interaction during particle internalization and endocytosis followed by blockade
      of TLR9 function could result in less efficient sensing of HCV RNA by TLR7, with
      impaired production of IFN-alpha. This finding is important for our understanding
      of HCV-DC interaction and immunopathogenesis of HCV infection.

PMID- 19183808
TI  - The effect of transposable element insertions on gene expression evolution in
      rodents.
AB  - BACKGROUND: Many genomes contain a substantial number of transposable elements
      (TEs), a few of which are known to be involved in regulating gene expression.
      However, recent observations suggest that TEs may have played a very important
      role in the evolution of gene expression because many conserved non-genic
      sequences, some of which are know to be involved in gene regulation, resemble
      TEs. RESULTS: Here we investigate whether new TE insertions affect gene
      expression profiles by testing whether gene expression divergence between mouse
      and rat is correlated to the numbers of new transposable elements inserted near
      genes. We show that expression divergence is significantly correlated to the
      number of new LTR and SINE elements, but not to the numbers of LINEs. We also
      show that expression divergence is not significantly correlated to the numbers of
      ancestral TEs in most cases, which suggests that the correlations between
      expression divergence and the numbers of new TEs are causal in nature. We
      quantify the effect and estimate that TE insertion has accounted for
      approximately 20% (95% confidence interval: 12% to 26%) of all expression profile
      divergence in rodents. CONCLUSIONS: We conclude that TE insertions may have had a
      major impact on the evolution of gene expression levels in rodents.

PMID- 19183809
TI  - Chaotic signatures of heart rate variability and its power spectrum in health,
      aging and heart failure.
AB  - A paradox regarding the classic power spectral analysis of heart rate variability
      (HRV) is whether the characteristic high- (HF) and low-frequency (LF) spectral
      peaks represent stochastic or chaotic phenomena. Resolution of this fundamental
      issue is key to unraveling the mechanisms of HRV, which is critical to its proper
      use as a noninvasive marker for cardiac mortality risk assessment and
      stratification in congestive heart failure (CHF) and other cardiac dysfunctions.
      However, conventional techniques of nonlinear time series analysis generally lack
      sufficient sensitivity, specificity and robustness to discriminate chaos from
      random noise, much less quantify the chaos level. Here, we apply a 'litmus test'
      for heartbeat chaos based on a novel noise titration assay which affords a
      robust, specific, time-resolved and quantitative measure of the relative chaos
      level. Noise titration of running short-segment Holter tachograms from healthy
      subjects revealed circadian-dependent (or sleep/wake-dependent) heartbeat chaos
      that was linked to the HF component (respiratory sinus arrhythmia). The relative
      'HF chaos' levels were similar in young and elderly subjects despite proportional
      age-related decreases in HF and LF power. In contrast, the near-regular heartbeat
      in CHF patients was primarily nonchaotic except punctuated by undetected ectopic
      beats and other abnormal beats, causing transient chaos. Such profound circadian
      , age- and CHF-dependent changes in the chaotic and spectral characteristics of
      HRV were accompanied by little changes in approximate entropy, a measure of
      signal irregularity. The salient chaotic signatures of HRV in these subject
      groups reveal distinct autonomic, cardiac, respiratory and circadian/sleep-wake
      mechanisms that distinguish health and aging from CHF.

PMID- 19183810
TI  - Varicones and growth cones: two neurite terminals in PC12 cells.
AB  - The rat adrenal pheochromocytoma PC12 cell line is one of the traditional models
      for the study of neurite outgrowth and growth cone behavior. To clarify to what
      extent PC12 neurite terminals can be compared to neuronal growth cones, we have
      analyzed their morphology and protein distribution in fixed PC12 cells by
      immunocytochemistry. Our results show that that PC12 cells display a special kind
      of neurite terminal that includes a varicosity in close association with a growth
      cone. This hybrid terminal, or "varicone", is characterized by the expression of
      specific markers not typically present in neuronal growth cones. For example, we
      show that calpain-2 is a specific marker of varicones and can be detected even
      before the neurite develops. Our data also shows that a fraction of PC12 neurites
      end in regular growth cones, which we have compared to hippocampal neurites as a
      control. We also report the extraordinary incidence of varicones in the
      literature referred to as "growth cones". In summary, we provide evidence of two
      different kinds of neurite terminals in PC12 cells, including a PC12-specific
      terminal, which implies that care must be taken when using them as a model for
      neuronal growth cones or neurite outgrowth.

PMID- 19183811
TI  - Forest structure and roe deer abundance predict tick-borne encephalitis risk in
      Italy.
AB  - BACKGROUND: The Western Tick-borne encephalitis (TBE) virus often causes
      devastating or lethal disease. In Europe, the number of human TBE cases has
      increased dramatically over the last decade, risk areas are expanding and new
      foci are being discovered every year. The early localisation of new TBE foci and
      the identification of the main risk factors associated with disease emergence
      represent a priority for the public health community. Although a number of socio
      economic parameters have been suggested to explain TBE upsurges in eastern
      Europe, the principal driving factors in relatively stable western European
      countries have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: In this
      paper, we analyse the correlation between the upsurge of TBE in 17 alpine
      provinces in northern Italy from 1992 to 2006 with climatic variables, forest
      structure (as a proxy for small mammal reservoir host abundance), and abundance
      of the principal large vertebrate tick host (roe deer), using datasets available
      for the last 40 years. No significant differences between the pattern of changes
      in climatic variables in provinces where TBE has emerged compared to provinces
      were no clinical TBE cases have been observed to date. Instead, the best model
      for explaining the increase in TBE incidence in humans in this area include
      changes in forest structure, in particular the ratio of coppice to high stand
      forest, and the density of roe deer. CONCLUSION/SIGNIFICANCE: Substantial changes
      in vegetation structure that improve habitat suitability for the main TBE
      reservoir hosts (small mammals), as well as an increase in roe deer abundance due
      to changes in land and wildlife management practices, are likely to be among the
      most crucial factors affecting the circulation potential of Western TBE virus
      and, consequently, the risk of TBE emergence in humans in western Europe. We
      believe our approach will be useful in predicting TBE risk on a wider scale.

PMID- 19183812
TI  - Confusion and conflict in assessing the physical activity status of middle-aged
      men.
AB  - BACKGROUND: Physical activity (including exercise) is prescribed for health and
      there are various recommendations that can be used to gauge physical activity
      status. The objective of the current study was to determine whether twelve
      commonly-used physical activity recommendations similarly classified middle-aged
      men as sufficiently active for general health. METHODS AND FINDINGS: We examined
      the commonality in the classification of physical activity status between twelve
      variations of physical activity recommendations for general health in ninety men
      aged 45-64 years. Physical activity was assessed using synchronised accelerometry
      and heart rate. Using different guidelines but the same raw data, the proportion
      of men defined as active ranged from to 11% to 98% for individual recommendations
      (median 73%, IQR 30% to 87%). There was very poor absolute agreement between the
      recommendations, with an intraclass correlation coefficient (A,1) of 0.24 (95%
      CI, 0.15 to 0.34). Only 8% of men met all 12 recommendations and would therefore
      be unanimously classified as active and only one man failed to meet every
      recommendation and would therefore be unanimously classified as not sufficiently
      active. The wide variability in physical activity classification was explained by
      ostensibly subtle differences between the 12 recommendations for thresholds
      related to activity volume (time or energy), distribution (e.g., number of days
      of the week), moderate intensity cut-point (e.g., 3 vs. 4 metabolic equivalents
      or METs), and duration (including bout length). CONCLUSIONS: Physical activity
      status varies enormously depending on the physical activity recommendation that
      is applied and even ostensibly small differences have a major impact.
      Approximately nine out of every ten men in the present study could be variably
      described as either active or not sufficiently active. Either the effective dose
      or prescription that underlies each physical activity recommendation is different
      or each recommendation is seeking the same prescriptive outcome but with variable
      success.

PMID- 19183813
TI  - On the evolution of the standard genetic code: vestiges of critical scale
      invariance from the RNA world in current prokaryote genomes.
AB  - Herein two genetic codes from which the primeval RNA code could have originated
      the standard genetic code (SGC) are derived. One of them, called extended RNA
      code type I, consists of all codons of the type RNY (purine-any base-pyrimidine)
      plus codons obtained by considering the RNA code but in the second (NYR type) and
      third (YRN type) reading frames. The extended RNA code type II, comprises all
      codons of the type RNY plus codons that arise from transversions of the RNA code
      in the first (YNY type) and third (RNR) nucleotide bases. In order to test if
      putative nucleotide sequences in the RNA World and in both extended RNA codes,
      share the same scaling and statistical properties to those encountered in current
      prokaryotes, we used the genomes of four Eubacteria and three Archaeas. For each
      prokaryote, we obtained their respective genomes obeying the RNA code or the
      extended RNA codes types I and II. In each case, we estimated the scaling
      properties of triplet sequences via a renormalization group approach, and we
      calculated the frequency distributions of distances for each codon. Remarkably,
      the scaling properties of the distance series of some codons from the RNA code
      and most codons from both extended RNA codes turned out to be identical or very
      close to the scaling properties of codons of the SGC. To test for the robustness
      of these results, we show, via computer simulation experiments, that random
      mutations of current genomes, at the rates of 10(-10) per site per year during
      three billions of years, were not enough for destroying the observed patterns.
      Therefore, we conclude that most current prokaryotes may still contain relics of
      the primeval RNA World and that both extended RNA codes may well represent two
      plausible evolutionary paths between the RNA code and the current SGC.

PMID- 19183814
TI  - Facilitated monocyte-macrophage uptake and tissue distribution of
      superparmagnetic iron-oxide nanoparticles.
AB  - BACKGROUND: We posit that the same mononuclear phagocytes (MP) that serve as
      target cells and vehicles for a host of microbial infections can be used to
      improve diagnostics and drug delivery. We also theorize that physical and
      biological processes such as particle shape, size, coating and opsonization that
      affect MP clearance of debris and microbes can be harnessed to facilitate uptake
      of nanoparticles (NP) and tissue delivery. METHODS: Monocytes and monocyte
      derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide
      (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake
      and distribution. IgG coated SPIO was synthesized by covalent linkage and uptake
      into monocytes and MDM investigated related to size, time, temperature,
      concentration, and coatings. SPIO and IgG SPIO were infused intravenously into
      naive mice. T(2) measures using magnetic resonance imaging (MRI) were used to
      monitor tissue distribution in animals. RESULTS: Oxidation of dextran on the SPIO
      surface generated reactive aldehyde groups and permitted covalent linkage to
      amino groups of murine and human IgG and F(ab')(2) fragments and for Alexa
      Fluor(R) 488 hydroxylamine to form a Schiff base. This labile intermediate was
      immediately reduced with sodium cyanoborohydride in order to stabilize the NP
      conjugate. Optical density measurements of the oxidized IgG, F(ab')(2), and/or
      Alexa Fluor(R) 488 SPIO demonstrated approximately 50% coupling yield. IgG-SPIO
      was found stable at 4 degrees C for a period of 1 month during which size and
      polydispersity index varied little from 175 nm and 200 nm, respectively. In
      vitro, NP accumulated readily within monocyte and MDM cytoplasm after IgG-SPIO
      exposure; whereas, the uptake of native SPIO in monocytes and MDM was 10-fold
      less. No changes in cell viability were noted for the SPIO-containing monocytes
      and MDM. Cell morphology was not changed as observed by transmission electron
      microscopy. Compared to unconjugated SPIO, intravenous injection of IgG-SPIO
      afforded enhanced and sustained lymphoid tissue distribution over 24 hours as
      demonstrated by MRI. CONCLUSIONS: Facilitated uptake of coated SPIO in monocytes
      and MDM was achieved. Uptake was linked to particle size and was time and
      concentration dependent. The ability of SPIO to be rapidly taken up and
      distributed into lymphoid tissues also demonstrates feasibility of macrophage
      targeted nanoformulations for diagnostic and drug therapy.

PMID- 19183816
TI  - First-episode drug-induced psychosis: a medium term follow up study reveals a
      high-risk group.
AB  - BACKGROUND: Little is known about first-episode drug-induced psychosis (F19.5).
      OBJECTIVES: To examine the incidence, course, diagnostic stability, and outcomes
      of first-episode drug-induced psychosis (F19.5), and compare with first-episode
      schizophrenia (F20-21). METHOD: An observational database was set up on all
      patients aged 16 and over with a first episode psychosis living in a county in
      Northern England between October 1998 and October 2005. Data were collected at
      presentation and annual follow-up. Information on patients with an ICD-10
      diagnosis of either drug-induced psychosis (F19.5) or schizophrenia (F20) was
      compared. RESULTS: There was no significant difference between the two groups in
      levels of hospitalisation and violence. Patients with a drug-induced psychosis
      were more likely to lose contact with services, and a third developed a
      schizophrenia-spectrum disorder. CONCLUSIONS: Increased attention should be paid
      to maintaining engagement with this high-risk group who have a high rate of
      transition to schizophrenia.

PMID- 19183817
TI  - Measurement of problems in activities and participation in patients with anxiety,
      depression and schizophrenia using the ICF checklist.
AB  - BACKGROUND: Although disability in persons with anxiety and depression disorders
      has been measured, the problem with some studies is that they use tools that
      measure the state of health, when the subjective nature of the measuring system
      does not permit the exact measurement of disability. The ICF Checklist provides a
      new paradigm for measuring disability that focuses more on the consequences than
      on the illness itself. The objective of this study is to compare the problems in
      Activities and Participation observed in patients with anxiety, depressive, and
      schizophrenic disorders, using the ICF Checklist. METHODS: The ICF Checklist was
      administered to 72 patients with anxiety or depressive disorders and 28 patients
      with schizophrenia. They were diagnosed in accordance with the criteria of the
      ICD-10. Chi-square analysis was carried out to determine the differences between
      the groups studied with respect to the Activities and Participation scales of the
      ICF Checklist and the nominal data of the socio-demographic variables. RESULTS:
      The group with anxiety-depression had a higher percentage of patients with
      problems preparing meals (30.6%) and achieving intimate relationships (59.7%)
      than did the patients with schizophrenia. The group with schizophrenia had a
      higher percentage of patients who had problems watching (39.3%), listening
      (42.9%), undertaking a single task (60.7%), communicating, fine hand use (57.1%),
      using transportation (64.3%), and caring for body parts (67.9%), among others.
      CONCLUSIONS: The ICF Checklist permits comparison of the impact mental disorders
      have on patients. It provides a more appropriate way of evaluating these
      illnesses in relation to others, considering not only the question of mortality
      but also the years lived with disability due to illness.

PMID- 19183815
TI  - The Staphylococcus aureus response to unsaturated long chain free fatty acids:
      survival mechanisms and virulence implications.
AB  - Staphylococcus aureus is an important human commensal and opportunistic pathogen
      responsible for a wide range of infections. Long chain unsaturated free fatty
      acids represent a barrier to colonisation and infection by S. aureus and act as
      an antimicrobial component of the innate immune system where they are found on
      epithelial surfaces and in abscesses. Despite many contradictory reports, the
      precise anti-staphylococcal mode of action of free fatty acids remains
      undetermined. In this study, transcriptional (microarrays and qRT-PCR) and
      translational (proteomics) analyses were applied to ascertain the response of S.
      aureus to a range of free fatty acids. An increase in expression of the sigma(B)
      and CtsR stress response regulons was observed. This included increased
      expression of genes associated with staphyloxanthin synthesis, which has been
      linked to membrane stabilisation. Similarly, up-regulation of genes involved in
      capsule formation was recorded as were significant changes in the expression of
      genes associated with peptidoglycan synthesis and regulation. Overall,
      alterations were recorded predominantly in pathways involved in cellular
      energetics. In addition, sensitivity to linoleic acid of a range of defined
      (sigB, arcA, sasF, sarA, agr, crtM) and transposon-derived mutants (vraE,
      SAR2632) was determined. Taken together, these data indicate a common mode of
      action for long chain unsaturated fatty acids that involves disruption of the
      cell membrane, leading to interference with energy production within the
      bacterial cell. Contrary to data reported for other strains, the clinically
      important EMRSA-16 strain MRSA252 used in this study showed an increase in
      expression of the important virulence regulator RNAIII following all of the
      treatment conditions tested. An adaptive response by S. aureus of reducing cell
      surface hydrophobicity was also observed. Two fatty acid sensitive mutants
      created during this study were also shown to diplay altered pathogenesis as
      assessed by a murine arthritis model. Differences in the prevalence and clinical
      importance of S. aureus strains might partly be explained by their responses to
      antimicrobial fatty acids.

PMID- 19183818
TI  - Evaluation of consortia of microorganisms for efficient removal of hexavalent
      chromium from industrial wastewater.
AB  - The Chromium (Cr) uptake ability of Cr-resistant bacterium Bacillus
      thuringiensis, yeast Candida etschellsii, and a protozoan Stylonychia mytilus,
      isolated from industrial waste water, was evaluated individually and in different
      combinations. It was found that the three types of microorganisms grown together
      in a culture medium could collectively uptake 90% of Cr(6+) from the culture
      medium as against 82% by bacterium + protozoan or yeast + protozoan combined
      culture, each. Consortium of bacterium, yeast and ciliates therefore could make
      much more efficient inoculum for remediation of Cr-contaminated industrial waste
      water.

PMID- 19183819
TI  - Personal and static sample measurements of asbestos fibres during two abatement
      projects.
AB  - Exposure assessment was performed during the abatement of amosite containing
      material (ACM) and chrysotile containing material (CCM). Mean fibre
      concentrations (MFC) in breathing zone (BZ) were 20.6+/-7.9 f/cc and 6.3+/-2.2
      f/cc during abatements of ACM and CCM, respectively. At the fixed station, MFC
      were 5.4+/-3.5 f/cc for ACM and 2.9 f/cc+/-1.6 for CCM. For observer's BZ, MFC
      were 3.1+/-1.3 f/cc (ACM) and 1.8 f/cc (CCM) during the abatement. Though
      elevated, area and observer-type samples clearly underestimate exposure. Exposure
      remained unacceptable in the worksite with the class of respiratory protection
      used.

PMID- 19183820
TI  - Zinc, cadmium and lead accumulation and characteristics of rhizosphere microbial
      population associated with hyperaccumulator Sedum alfredii Hance under natural
      conditions.
AB  - A field survey was conducted to study the characteristics of zinc, cadmium, and
      lead accumulation and rhizosphere microbial population associated with
      hyperaccumulator Sedum alfredii Hance growing natively on an old lead/zinc mining
      site. We found significant hyperaccumulation of zinc and cadmium in field samples
      of S. alfredii, with maximal shoot concentrations of 9.10-19.61 g kg(-1) zinc and
      0.12-1.23 g kg(-1) cadmium, shoot/root ratios ranging from 1.75 to 3.19 (average
      2.54) for zinc, 3.36 to 4.43 (average 3.85) for cadmium, shoot bioaccumulation
      factors of zinc and cadmium being 1.46-4.84 and 7.35-17.41, respectively. While
      most of lead was retained in roots, thus indicating exclusion as a tolerance
      strategy for lead. Compared to the non-rhizosphere soil, organic matter and total
      nitrogen and phosphorus content, CEC and water extractable zinc, cadmium, and
      lead concentration were significantly higher, but pH was smaller in rhizosphere
      soil. The rhizosphere soil of S. alfredii harbored a wide variety of
      microorganism. In general, significantly higher numbers of culturable bacteria,
      actinomycetes, and fungi were found in the rhizosphere compared to bulk soil,
      confirming the stimulatory effect of the S. alfredii rhizosphere on microbial
      growth and proliferation. Analyses of BIOLOG data also showed that the growth of
      S. alfredii resulted in observable changes in BIOLOG metabolic profiles,
      utilization ability of different carbon substrates of microbial communities in
      the rhizosphere soil were also higher than the non-rhizosphere, confirming a
      functional effect of the rhizosphere of S. alfredii on bacterial population.

PMID- 19183821
TI  - Mississippi oxbow lake sediment quality during an artificial flood.
AB  - Surface sediment quality was assessed during a 35-day artificial flood in a
      shallow (<1.5 m) oxbow lake along the Coldwater River, Mississippi, using
      Hyalella azteca 28-day bioassays. Seventeen pesticides were monitored in
      sediments before, during and after flooding, with increases in atrazine and
      metolachlor concentrations coinciding with two unexpected storm events, 51 and 56
      mm, during and after flooding, respectively. Mean 28-day H. azteca survival was
      >85% throughout this study. However, growth was affected at three sites during
      flooding with limited growth recovery after flooding. Patterns in observed growth
      impairment were associated with changes in atrazine (R(2)=0.524) and fipronil
      sulfone (R(2)=0.584) concentrations.

PMID- 19183822
TI  - Deposition of organochlorine pesticides, PCBs (Aroclor 1268), and PBDEs in
      selected plant species from a Superfund Site at Brunswick, Georgia, USA.
AB  - Deposition of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs)
      and polybrominated diphenyl ethers (PBDEs) were measured in Loblolly pine needles
      (Pinus taeda) collected in and around a Linden Chemicals and Plastics (LCP)
      Superfund Site at Brunswick, Georgia, USA. For the comparison, foliage of eastern
      red cedar (Juniperus virginiana) was also collected to monitor contaminant
      levels. This study revealed that concentrations of OCPs, PCBs and PBDEs ranged
      from 0.75-10, 3.4-15 to 0.05-3, ng/g wet wt, respectively in both plant species.
      Total OCPs concentrations in pine needles decreased from 10 to 2.3 ng/g; and
      total PCBs decreased from 28 to 9.3 ng/g between 1997 and 2006. To our knowledge,
      this is the first report on PBDEs concentrations in pine needles and red cedar
      foliage samples from the Superfund Site at Brunswick, Georgia, USA.

PMID- 19183823
TI  - Determination of the phenoxyacid herbicides MCPA, mecoprop and 2,4-D in kidney
      tissue using liquid chromatography with electrospray tandem mass spectrometry.
AB  - An analytical method was developed to determine the phenoxyacid herbicides 2,4-D,
      MCPA and mecoprop in kidney tissue from animals where poisoning is suspected.
      Samples were Soxhlet extracted using diethyl ether and the extracts cleaned-up
      using anion exchange solid phase extraction cartridges. Analysis was performed
      using liquid chromatography with negative-ion electrospray tandem mass
      spectrometry (LC-MS/MS). The method was evaluated by analysing control kidney
      samples fortified at 1 and 5 mg/kg. Mean recoveries ranged from 82 to 93% with
      relative standard deviations from 3.2 to 19%. The limit of detection was
      estimated to be 0.02 mg/kg.

PMID- 19183824
TI  - Demineralized dentin matrix acts as a scaffold for repair of articular cartilage
      defects.
AB  - Articular cartilage repair remains a major obstacle in tissue engineering. In the
      present study, we investigated the potential for demineralized dentin matrix
      (DDM; organic material derived from dentin) obtained from extracted teeth to be
      used as bone graft material. To evaluate the extent to which DDM induces
      osteochondral regeneration, we implanted DDM from bovine teeth in rabbit knees
      with full-thickness articular cartilage defects. Thirty-three 13-week-old male
      rabbits weighing 2.5-3.0 kg were randomly assigned to a control group (n = 11)
      and two experimental groups (n = 11 for each group). The knees were divided into
      three groups according to the subsequent treatment: in group I (n = 22), the
      control group, the defect was left untreated; and in groups II (n = 22) and III
      (n = 22), 50 and 100 mg of DDM, respectively, was implanted. The rabbits were
      killed 1, 3, 6, or 9 weeks after the surgical procedure, and the knees were
      collected. The harvested tissues were examined radiographically and
      histologically. The 100-mg DDM group (group III) had significantly more new bone
      forming inside the defect (as measured using the BV/TV value) compared with the
      other two groups as early as at week 3 postoperatively, but thereafter, the
      difference gradually decreased. Cartilage repair in the surface region remained
      significantly better in group III because hyaline-like cartilage appeared in the
      peripheral area of the defect at week 6 and the surface was covered with hyaline
      like cartilage with a thickness similar to that of normal cartilage at week 9. In
      conclusion, the results of this study suggest that DDM acts as a scaffold for
      osteochondral regeneration, yielding active new bone formation early in the
      postoperative period. Thus, DDM may represent an effective bone implant material.

PMID- 19183826
TI  - Classification of female genito-urinary tract fistula: a comprehensive review.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this paper is to review proposed
      classifications for genito-urinary fistulae. METHODS: A comprehensive literature
      review of historical texts, peer review publications, and abstracts was used to
      compile a listing of the existing genito-urinary fistula classification systems.
      RESULTS: The absence of an accepted standardized classification for female genito
      urinary fistulae has resulted in the proliferation of a number of individually
      devised categorizations. Fistulae are described by size, location, degree of
      vaginal scarring, and type (whether it involves the bladder, rectum, intestines,
      uterus, etc). In addition, most classification systems have not been subjected to
      outcomes research, making them primarily descriptive in nature. CONCLUSIONS:
      There is a lack of consensus among fistula surgeons in adopting a standardized
      classification system or systems. Comparative assessment of studies and outcomes
      is not possible without a standardized classification system. Currently, there is
      no accepted standardized classification for female genito-urinary fistula.

PMID- 19183828
TI  - Upgrade of an optical navigation system with a permanent electromagnetic position
      control: a first step towards "navigated control" for liver surgery.
AB  - INTRODUCTION: The main problems of navigation in liver surgery are organ movement
      and deformation. With a combination of direct optical and indirect
      electromagnetic tracking technology, visualisation and positional control of
      surgical instruments within three-dimensional ultrasound data and registration of
      organ movements can be realised simultaneously. METHODS: Surgical instruments for
      liver resection were localised with an infrared-based navigation system
      (Polaris). Movements of the organ itself were registered using an electromagnetic
      navigation system (Aurora). The combination of these two navigation techniques
      and a new surgical navigation procedure focussed on a circumscribed critical
      dissection area were applied for the first time in liver resections. RESULTS:
      This new technique was effectively implemented. The position of the surgical
      instrument was localised continuously. Repeated position control with observation
      of the navigation screen was not necessary. During surgical resection, a sonic
      warning signal was activated when the surgical instrument entered a "no touch"
      area--an area of reduced safety margin. CONCLUSION: Optical tracking of surgical
      instruments and simultaneous electromagnetic registration of organ position is
      feasible in liver resection.

PMID- 19183825
TI  - Predictors of outcomes in the treatment of urge urinary incontinence in women.
AB  - INTRODUCTION AND HYPOTHESIS: Women with urge predominant urinary incontinence
      received active intervention (drug therapy alone or combined with behavioral
      therapy) for 10 weeks, then stopped all therapy and were followed for 6 months
      more. In this planned secondary analysis, we aimed to identify predictors of
      therapeutic success at 10 weeks (> or =70% reduction in incontinence) and of
      ability to discontinue treatment and sustain improvements 6 months later.
      METHODS: Using data from 307 women, we performed logistic regression to identify
      predictors for outcomes described above. RESULTS: After controlling for group,
      only younger age was associated with short-term success (OR 0.8, 95% CI 0.66,
      0.96). At 6 months, controlling for group and short-term outcome, only greater
      anterior vaginal wall prolapse was associated with successful discontinuation
      (POP-Q point Aa; OR 1.33, 95% CI 1.03, 1.7). CONCLUSION: These findings are not
      of sufficient strength to justify withholding conservative therapies but might be
      used to promote realistic expectations when counseling patients.

PMID- 19183829
TI  - Hepatocellular carcinoma with extensive peliotic change.
AB  - Peliosis hepatis is a rare lesion histologically characterized by multiple
      cavities representing dilated sinusoids filled with blood in the liver. Although
      it has been observed in the liver parenchyma in association with several diseases
      and medications, there are few reports of nodules of hepatocellular carcinoma
      (HCC) showing extensive peliotic change. We describe a case of HCC showing
      extensive peliotic change in the cancer nodule. A 73-year-old man with a liver
      tumor was referred to our hospital for further investigation. Abdominal
      ultrasonography revealed an 8-cm hyperechoic lesion with a halo and mosaic
      pattern in segment 8 (S8) of the liver. Dynamic magnetic resonance imaging of the
      liver showed early irregular enhancement of the peripheral part of the lesion,
      and the effect persisted into the late phase, spreading into the central part of
      the nodule. Hepatic arteriography showed the "cotton-wool" sign, usually observed
      in cavernous hemangiomas. Fine-needle aspiration biopsy revealed the diagnosis of
      HCC. Anterior sectionectomy of the liver was conducted. Histological examination
      of the resected specimen showed that the tumor was a well-differentiated HCC with
      extensive dilated sinusoid-like structures in the main portion of the nodule,
      suggestive of peliotic change.

PMID- 19183830
TI  - Acinar cell carcinomas with exophytic growth and intraductal pancreatic duct
      invasion: peculiar multislice computed tomographic picture.
AB  - On an ultrasound and multislice computed tomography (MSCT), a 76-year-old woman
      was found to have a huge mass lesion in the pancreatic head. MSCT showed 8.4 cm
      well-enhancing exophytic tumor of the pancreatic head which also protruded into
      the duodenum. A tongue-like protrusion into the main pancreatic duct was
      depicted. Laboratory data showed elevated carbohydrate antigen 19-9. Whipple's
      operation was performed. The pathological diagnosis was acinar cell carcinoma
      (ACC) originating in the pancreatic head and directly invading through the
      duodenal wall and the main pancreatic duct, without any lymph node involvement. A
      peculiar ACC with good enhancement, exophytic picture and tongue-like protrusion
      into the main pancreatic duct on MSCT is presented.

PMID- 19183831
TI  - Usefulness of measuring hepatic functional volume using Technetium-99m galactosyl
      serum albumin scintigraphy in bile duct carcinoma: report of two cases.
AB  - We report the usefulness of measuring functional liver volume in two patients
      undergoing hepatectomy. Case 1 involved a 47-year-old man with hepatitis B virus
      infection. The indocyanine green test retention rate at 15 min (ICGR15) was 14%.
      Liver uptake ratio (LHL15) by technetium-99 m galactosyl human serum albumin
      ((99m)Tc-GSA) liver scintigraphy was 0.91. The patient displayed hilar bile duct
      carcinoma necessitating right hepatectomy. After preoperative portal vein
      embolization (PVE), future remnant liver volume became 54% and functional volume
      by (99m)Tc-GSA became 79%. Although the permitted resected liver volume was lower
      than the liver volume, scheduled hepatectomy was performed following the results
      of functional liver volume. Case 2 involved a 75-year-old man with diabetes.
      ICGR15 was 27.4% and LHL15 was 0.87. The patient displayed bile duct carcinoma
      located in the upper bile duct with biliary obstruction in the right lateral
      sector. The right hepatectomy was scheduled. After PVE, future remnant volume
      became 68% and functional volume became 88%. Although ICGR15 was worse as 31%,
      planned hepatectomy was performed due to the results of functional volume. In the
      liver with biliary obstruction or portal embolization, functional liver volume is
      decreased more than morphological volume. Measurement of functional volume
      provides useful information for deciding operative indication.

PMID- 19183832
TI  - p53 gene mutation and p53 protein overexpression in a patient with simultaneous
      double cancer of the gallbladder and bile duct associated with pancreaticobiliary
      maljunction.
AB  - Pancreaticobiliary maljunction (PBM) is associated with the occurrence of biliary
      cancer due to pancreatobiliary reflux. We present a case of simultaneous double
      cancer of the gallbladder and bile duct. A 77-year-old woman who had jaundice,
      intra- and extra-hepatic biliary ductal dilatation and a space-occupying lesion
      in the gallbladder and lower bile duct underwent pancreatoduodenectomy. The
      gallbladder cancer showed papillary carcinoma without mutation of the K-ras gene
      and with p53 non-sense mutation of CCA (Pro) to CA (Stop) on codon 301 in exon 8.
      The bile duct cancer revealed a well-differentiated adenocarcinoma without
      mutation of the K-ras gene and with p53 miss-sense mutation of GTG (Val) to GAG
      (Glu) on codon 272 in exon 8. There were no mutations of either the K-ras or p53
      gene in non-cancerous epithelia. In contrast, only the mucosa of the common
      channel had p53 protein accumulation and high cell proliferation activity.
      Therefore, the genetic pathway might be the same in both the gallbladder and bile
      duct cancer, and a high potential for carcinogenesis might be present in the
      epithelium of the common channel in patients with PBM.

PMID- 19183833
TI  - Impact of internal biliary drainage after pancreaticoduodenectomy.
AB  - BACKGROUND: Bile acid has an important role in protecting immune systems related
      to gut-associated lymphoid tissue. This study was designed to evaluate the
      effects of internal biliary drainage after a pancreaticoduodenectomy (PD) on
      postoperative nutrition and complications in a randomized study. METHODS: The
      authors compared the morbidity, mortality, and postoperative nutritional status
      of 46 patients who had a hepaticojejunostomy (HJ) with a stented external biliary
      drainage (group E) or with a non-stented internal biliary drainage (group I)
      after a PD. RESULTS: Systemic infection was recognized in four patients in group
      E, while no patients in group I. Transthyretin at postoperative 28 days in group
      I was 15.6 +/- 6.2, higher than that in group E. Retinol-binding protein at
      postoperative 28 days in group I was 2.6 +/- 1.0 and also higher than that in
      group E. CONCLUSION: HJ with no-stented internal biliary drainage was not
      associated with systemic infections and mortality, but showed the possibility of
      improving nutritional status.

PMID- 19183834
TI  - Modified liver hanging maneuver with extraparenchymal isolation of the middle
      hepatic vein in left hepatectomy.
AB  - BACKGROUND/PURPOSE: The liver hanging maneuver has been employed mostly for right
      hepatectomy. After the space between the inferior vena cava and the liver
      parenchyma is bluntly dissected, a tape is passed through the space, with the
      upper end of the tape between the right hepatic vein and middle hepatic vein
      (MHV). We devised a modified maneuver with tape repositioning between the MHV and
      left hepatic vein (LHV) after extraparenchymal isolation of the MHV, in left
      hepatectomy with the caudate lobe and without the MHV. METHODS: The ligamentum
      venosum is divided. Traction of the cranial stump of the ligament in the cranial
      and left direction shows an avascular plane between the LHV and MHV, and enables
      the taping of each MHV and LHV. Finally, the upper end of the hanging tape is
      repositioned. RESULTS: This maneuver was successfully performed in three
      patients. CONCLUSIONS: The present maneuver is feasible and useful in left
      hepatectomy.

PMID- 19183835
TI  - Transient dynamic actin cytoskeletal change stimulates the osteoblastic
      differentiation.
AB  - Dynamic cytoskeletal changes appear to be one of intracellular signals that
      control cell differentiation. To test this hypothesis, we examined the effects of
      short-term actin cytoskeletal changes on osteoblastic differentiation. We found
      an actin polymerization interfering reagent, cytochalasin D, promoted
      osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells. We also
      found that these effects were mediated by the protein kinase D (PKD) pathway.
      Short-term cytochalasin D treatment increased alkaline phosphatase (ALP)
      activity, osteocalcin (OCN) secretion, and mineralization of the extracellular
      matrix in MC3T3-E1 cells, with temporary changes in actin cytoskeleton.
      Furthermore, the disruption of actin cytoskeleton induced phosphorylation of
      744/748 serine within the activation loop of PKD in a dose-dependent manner. The
      protein kinase C (PKC)/PKD inhibitor Go6976 suppressed cytochalasin D-induced
      acceleration of osteoblastic differentiation, whereas Go6983, a specific
      inhibitor of conventional PKCs, did not. Involvement of PKD signaling was
      confirmed by using small interfering RNA to knock down PKD. In addition, another
      actin polymerization interfering reagent, latrunculin B, also stimulated ALP
      activity and OCN secretion with PKD activation. On the other hand, the present
      data suggested that transient dynamic actin cytoskeletal reorganization could be
      a novel cellular signal that directly stimulated osteoblastic differentiation.

PMID- 19183836
TI  - Effects of risedronate or alfacalcidol on bone mineral density, bone turnover,
      back pain, and fractures in Japanese men with primary osteoporosis: results of a
      two-year strict observational study.
AB  - Although osteoporosis in men is already a major public health problem, there is
      still a dearth of data about the effects of risedronate in male osteoporosis,
      especially in Japanese with primary osteoporosis. Therefore, the objective of our
      study was to investigate the effects of risedronate on bone mineral density
      (BMD), bone turnover, back pain, and fractures in these patients prospectively
      for two years (at baseline, three months, six months, twelve months, and twenty
      four months) both longitudinally and compared with those of alfacalcidol. The
      subjects enrolled for this study were 66 Japanese male patients with untreated
      primary osteoporosis (mean age 63.52 +/- 8.7 years), who were divided into two
      groups (44 with risedronate and 22 with alfacalcidol). We measured BMD by dual
      energy X-ray absorptiometry at three sites-the lumbar spine, femoral neck, and
      distal radius. Risedronate treatment significantly increased BMD at the lumbar
      spine and at the femoral neck, reduced bone-specific alkaline phosphatase (BAP)
      and serum N-terminal telopeptide of type I collagen (NTx), and reduced back pain,
      both longitudinally and compared with alfacalcidol treatment. We observed a lower
      rate of incident fracture in risedronate users. However, multiple logistic
      regression analysis revealed that this trend was not statistically significant,
      possibly because of the small number of patients enrolled. These potentially
      beneficial effects of risedronate on bone in male patients with primary
      osteoporosis suggest the possibility that osteoporosis should be treated with
      risedronate regardless of gender in order to effectively prevent subsequent
      osteoporotic fractures.

PMID- 19183837
TI  - Molecular mechanisms underlying the effects of sex steroids on bone and mineral
      metabolism.
AB  - The multifarious functions of sex steroid receptors include a role as regulatory
      factors for bone and mineral metabolism in vivo. These functions are more complex
      than originally assumed. The finding of nuclear receptors in osseous tissue
      alludes to the existence of novel indirect and direct functions of bone tissue
      beyond skeletal support, hematopoiesis, and calcium homeostasis. Cell-specific
      gene targeting approaches are an extremely important technology for future
      studies that will need to be conducted to fully understand the molecular
      mechanisms underlying bone formation and metabolism.

PMID- 19183838
TI  - Microaneurysm number and distribution in the macula of Chinese type 2 diabetics
      with early diabetic retinopathy: a population-based study in Kinmen, Taiwan.
AB  - To explore the number and distribution of microaneurysms (MA) in the macula of
      type 2 diabetics in Kinmen, Taiwan and associated risks for early diabetic
      retinopathy (DR). A baseline mass screening extracts 971 type 2 diabetics between
      1991 and 1993 and follow-up eye screening at 1999 was then done. Number of MA was
      counted and associated systemic factors collected from a centered 45 degrees
      color fundus photograph of dilated eyes of type 2 diabetics (Topcon-NW5). Thirty
      three (6.2%, n = 527) had MA retinopathy. Those with one eye involved (n = 26)
      had two mean MA; those with bilateral involvement (n = 7) had four mean per eye.
      Most MA were located temporally (mean MA = 0.79), then superiorly (mean = 0.58),
      inferiorly (mean = 0.46) and nasal (mean = 0.28). MA occurred at the 6,000-microm
      outermost ring (mean = 1.51), then the 3,000-microm ring (mean = 0.35), the 1,500
      microm ring (mean = 0.26) and center 500 microm circle (mean = 0.01). After
      adjusting for confounding factors, early DR with MA was associated with longer
      duration of type 2 diabetes [odds ratios (OR) = 1.10, 95% confidence interval
      (CI) 1.00-1.21], higher glycosylated hemoglobin (OR = 1.36, 95%CI 1.11-1.66) and
      wider waist circumference (OR = 1.04, 95%CI 1.01-1.07). Our photograph grading
      system suggests that MA number and distribution at the macula may reflect
      severity of early DR and is a valid tool for predicting the progression of DR.
      Identifying those factors associated with MA only DR is important in developing
      prevention strategies for this early microvascular complication of type 2
      diabetes.

PMID- 19183839
TI  - Epidemiology of type 1 diabetes among Silesian children aged 0-14 years, 1989
      2005.
AB  - The aim of this study was to estimate the present Polish incidence rate of
      diabetes mellitus type 1 in children aged 0-14. The research was conducted
      between 1989 and 2005 among the children of Upper Silesia region (Poland), being
      the part of the EURODIAB program, according to all criteria of this project.
      During this period, 1,385 new cases (720 boys) of diabetes mellitus type 1 were
      recognized. The analysis of the standardized incidence rates performed after
      dividing into shorter periods (1989-1994, 1995-1999, 2000-2005) showed a sharp
      increase from 5.80/10(5)/year through 9.54/10(5)/year to 15.26/10(5)/year,
      respectively, in the periods. Analysis of age subgroups showed the greatest
      increase in the incidence rate among the younger children: 3.59 times for
      children aged 0-4, 3.40 times for children aged 5-9 and 2.08 times for children
      aged 10-14. No significant difference of incidence rate between boys and girls
      was established. Such high increase of incidence rate of diabetes mellitus type 1
      (above 260%) noted since 1989 shows a secular trend of an epidemic of diabetes
      mellitus type 1 in Poland and a conversion from countries with the lower
      incidence rates in Europe to the countries with the highest incidence rates.

PMID- 19183840
TI  - Profile of patients with diabetes in Eritrea: results of first phase registry
      analyses.
AB  - A cross-sectional descriptive study was done on patients recently entered into
      the National Diabetes Registry in Eritrea where the prevalence was estimated to
      be 2.2% based on patient information in 2004. Of the 627 patients with diabetes,
      two thirds were type 2. Although type 1 had poorer control (42.9%) than type 2
      (29.9%), some of the risk factors such as cholesterol (43.4 vs. 28.2%),
      triglyceride (23.4 vs. 12.8%), hypertension (55.2 vs. 12.7%) as well as BMI and
      waist/hip ratio were higher in type 2 than type 1. More than one-third (41.2%) of
      patients with type 2 compared to type 1 (19.5%) had complications, the commonest
      being retinopathy (33%) followed by foot ulcers (14%) and neuropathy (4%). Many
      of the diabetic patients demonstrated the presence of the metabolic syndrome
      components such as hypertension, obesity and dyslipidemia. The authors conclude
      that diabetes registry is invaluable in providing evidence-based prevention and
      control of the disease.

PMID- 19183841
TI  - Nateglinide versus repaglinide for type 2 diabetes mellitus in China.
AB  - The purpose of this study is to evaluate efficacy and safety of nateglinide
      tablet administration in comparison with those of repaglinide tablet as control
      on treating type 2 diabetes mellitus in China. Pooled-analysis with analysis of
      covariance (ANCOVA) method was applied to assess the efficacy and safety based on
      original data collected from four independent randomized clinical trials with
      similar research protocols. However meta-analysis was applied based on the
      outcomes of the four studies. The results by meta-analysis were comparable to
      those obtained by pooled-analysis. The means of HbA(1c), and fasting blood
      glucose in both the nateglinide and repaglinide groups were reduced significantly
      after 12 weeks duration but no statistical differences in reduction between the
      two groups. The adverse reaction rates were 9.89 and 6.51% in the nateglinide and
      repaglinide groups respectively, with the rate difference showing no statistical
      significance, and the Odds Ratio of adverse reaction rate (95% confidence
      interval) was 1.59 (0.99, 2.55). Both nateglinide and repaglinide administration
      have similarly significant effects on reducing HbA(1c) and FBG. However, the
      adverse reaction rate in the nateglinide group is higher than that in the latter
      using repaglinide but no statistical significance difference as revealed in the
      four clinical trials detailed below.

PMID- 19183842
TI  - Variants of the adiponectin gene and type 2 diabetes in a Polish population.
AB  - Several association studies of type 2 diabetes mellitus (T2DM) and adiponectin
      gene polymorphisms have been reported with conflicting results. Our aim was to
      search for the association of three polymorphisms (-11.391G>A, +45T>G, and
      +276G>T) in the adiponectin gene with T2DM and prediabetic quantitative traits in
      Polish Caucasians. The study groups comprised 495 unrelated T2DM cases and 435
      controls. We compared the distribution of genotypes between study groups. In
      addition, genotype-quantitative trait analyses were also done in the controls.
      The study subjects were genotyped using the restriction fragment length
      polymorphism technique. The frequencies of the minor alleles were as follows:
      10.6 versus 8.2% for -11.391G>A (p = 0.0722), 7.0 versus 8.0% for +45T>G (p =
      0.48), and 15.5% in T2DM versus 19.8% in controls (p = 0.0145) for +276G>T,
      respectively. The difference for genotype distribution between the groups was
      statistically significant (p = 0.0247) for the +276G>T variant: 71.31 versus
      62.99%, 26.46 versus 34.48% and 2.22 versus 2.53%, respectively, for GG, GT and
      TT. In quantitative traits analysis, the T allele of +276G>T was associated (p <
      0.05) with lower insulin resistance (HOMA-IR, fasting insulin) among controls.
      Additionally, the A allele at position -11.391 was associated (p < 0.05) with
      higher insulin resistance (HOMA-IR, fasting insulin). In multiple regression
      analysis, all identified association remained significant after the inclusion in
      the model of gender, BMI and age. In addition, in this model, -11.391G>A and
      +276G>T were independently associated with T2DM. Finally, we conclude that the
      adiponectin gene polymorphisms are associated with T2DM and prediabetic
      quantitative traits in Polish Caucasians.

PMID- 19183843
TI  - Alterations in L-arginine and inflammatory markers in type 2 diabetic patients
      with and without microalbuminuria.
AB  - Low-grade inflammation is closely involved in the pathogenesis of type 2 diabetes
      and associated micro- and macrovascular complications. The nitric oxide (NO)
      precursor L-arginine, is relevant to diverse pathological conditions including
      type 2 diabetes and its complications. High sensitive-CRP (hs-CRP), neopterin and
      arginine levels were measured in 46 normoalbuminuric, 45 microalbuminuric type 2
      diabetics and in 32 healthy controls in order to assess the relationship between
      markers of inflammation and L: -arginine. Hs-CRP concentrations were higher in
      microalbuminuric diabetic patients compared to normoalbuminuric patients and
      controls. Diabetics had higher serum and urine neopterin levels than controls.
      Urine neopterin and L-arginine levels differed significantly among diabetic
      patients with and without microalbuminuria. There were significant positive
      correlations between hs-CRP and BMI in healthy controls and diabetics with and
      without microalbuminuria. In microalbuminuric diabetics, hs-CRP correlated with
      microalbuminuria (MAU). Significant predictors for the development of
      microalbuminuria were higher postprandial glucose levels, lower creatinine
      clearance and lower serum L-arginine levels. Assessment of early markers of
      inflammation and endothelial function, such as neopterin and NO precursor L
      arginine, may help to predict incipient nephropathy more accurately in type 2
      diabetic patients.

PMID- 19183844
TI  - Paraclinoid aneurysm concealed by sphenoid wing meningioma.
AB  - The coexistence of brain tumours and aneurysms is rare. In all previously
      reported cases the aneurysm was detectable by angiography. We report here a case
      in which a paraclinoid internal carotid artery aneurysm was coexistent and
      concealed from angiographic detection by an adjacent parasellar meningioma.

PMID- 19183845
TI  - Social inequalities in the use of health care services after 8 years of health
      care reforms - a comparative study of the Baltic countries.
AB  - OBJECTIVE: In nineties, Estonia, Latvia and Lithuania have implemented a wide
      range of changes to health systems. The objective of this paper was to assess
      social inequalities in utilisation of, and access to, health care services in the
      late nineties. METHODS: The comparative NORBALT Survey conducted in 1999 is used.
      Direct standardization and logistic regression was applied to analyse primary,
      out-patient and hospital care utilisation, and self reported financial barriers,
      by socio-demographic and geographical variables. RESULTS: In all three countries
      social inequalities in utilization were large for out-patient specialist care,
      smaller or absent with regards to primary care or to hospitalisations.
      Inequalities were large and consistent in relationship to household income, less
      so in relationship to educational level. Inequalities in utilization of care were
      larger in Latvia as well in the self reported barriers to health care in absolute
      and relative terms were larger. CONCLUSIONS: After 8 years of reforms, important
      pro-rich inequalities in the use of health services existed. In Latvia, these
      inequalities were largest, possibly due to higher ratio of cost sharing as
      compared to Estonia and Lithuania.

PMID- 19183846
TI  - The reliability of the Minimum European Health Module.
AB  - OBJECTIVES: The Minimum European Health Module (MEHM) consists of 3 global
      questions concerning 3 health domains: self-perceived health, chronic conditions
      and long-term activity limitation. The objective of this paper is to evaluate the
      reliability of the MEHM. METHODS: Participants of the Belgian Food Consumption
      Survey were interviewed twice: 170 individuals were selected for the MEHM
      reliability evaluation. For each of the 3 questions Pearson and Kappa
      coefficients were estimated. Analyses were stratified by gender, age, education,
      language and time between the interviews. RESULTS: The Pearson correlations are
      between 0.73 and 0.81. The Kappa estimates are good or excellent: 0.74 (self
      perceived health), 0.77 (chronic conditions) and 0.68 (activity limitation). Also
      stratified analyses indicated in general an acceptable reliability. CONCLUSION:
      The MEHM has an acceptable reliability.

PMID- 19183847
TI  - Ebm@school--a curriculum of critical health literacy for secondary school
      students: results of a pilot study.
AB  - OBJECTIVES: Increasingly, patients and consumers are taking responsibility for
      their diagnostic and therapeutic decisions. This requires a certain amount of
      health literacy in order to critically assess the various procedures and
      products. The aim of this study was to develop and pilot test a curriculum of
      critical health literacy for secondary school students. METHODS: The curriculum
      is based on the concept of evidence-based medicine and consists of six modules.
      Development and pilot testing was performed with two classes of secondary school
      students (n = 45) in Grade 11. The Metaplan method was used to document feedback
      regarding teaching methods, worksheets, satisfaction and individually perceived
      benefits. Additionally, systematic observations by researchers were documented
      and students' presentations assessed. A sample of untrained students (n = 218)
      served as a control group. The Critical Health Competency Test was employed for
      evaluating competencies in critical health literacy. Data were analyzed
      qualitatively and person parameters were calculated. RESULTS: Overall, the pilot
      courses were well-accepted and have been proven to be feasible. Students'
      feedback guided revision of the curriculum. Trained students achieved
      significantly higher person parameters (+/- SD) than the control group: 597 (+/-
      79) versus 483 (+/- 94), p < 0.01, indicating enhancement of critical health
      competencies. CONCLUSION: Teaching critical health literacy to secondary school
      students is feasible and is likely to enhance the competence of critical health
      literacy. Further studies are needed to show the effectiveness of the
      intervention.

PMID- 19183848
TI  - The perspectives of studying multi-domain protein folding.
AB  - Most of fundamental studies on protein folding have been performed with small
      globular proteins consisting of a single domain. In vitro many of these proteins
      are well characterized by a reversible two-state folding scheme. However, the
      majority of proteins in the cell belong to the class of larger multi-domain
      proteins that often unfold irreversibly under in vitro conditions. This makes
      folding studies difficult or even impossible. In spite of these problems for many
      multi-domain proteins, folding has been investigated by classical refolding. Co
      translational folding of nascent polypeptide chains when synthesized by ribosomes
      has also been studied. Single molecule techniques represent a promising approach
      for future studies on the folding of multi-domain proteins, and tremendous
      advances have been made in these techniques in recent years. In particular,
      fluorescence-based methods can contribute significantly to an understanding of
      the fundamental principles of multi-domain protein folding.

PMID- 19183849
TI  - The regulation of cell proliferation by the papillomavirus early proteins.
AB  - The human papillomavirus (HPV) E6 and E7 oncogenes have direct effects on host
      cell proliferation. The viral E2 protein regulates transcription of E6 and E7 and
      thereby has an indirect effect on cell proliferation. In HPV-induced tumours,
      misappropriate random integration of the viral genome into the host chromosome
      often leads to disruption of the E2 gene and the loss of E2 expression. This
      results in cessation of the virus life cycle and the deregulation of E6 and E7
      and is an important step in tumourigenesis. However, prior to these integration
      events, E2 can interact directly with the E6 and E7 proteins and modulate their
      activities. E2 also interacts with a variety of host proteins, including the p53
      tumour suppressor protein. Here we outline evidence that suggests a role for E2
      in the regulation of cell proliferation, and we discuss the importance of this
      regulation in viral infection and cervical tumourigenesis.

PMID- 19183850
TI  - Epilepsy in cerebral glioma: timing of appearance and histological correlations.
AB  - PURPOSE: A prospective study of patients with glioma was carried out. Special
      attention was paid to the first seizure, to the histology, and to the efficacy
      and prophylactic role of antiepileptic drugs (AEDs). Prognostic factors were
      analyzed. METHODS: Between February 1st 2004 and April 1st 2006 patients who
      underwent surgical treatment at the Neurosurgery Department of Bolzano for
      primary or recurrent glioma were prospectively followed until April 1st 2007.
      Seizures at onset occurring in the absence of interictal epileptiform
      abnormalities were regarded as remote symptomatic seizures and not treated.
      RESULTS: Sixty-four individuals were registered in the study; epilepsy diagnosis
      was made in 27 cases and in 24 of these seizures were the onset symptom. The
      correlation with histological grading showed that seizures were more frequent in
      low-grade glioma and in secondary glioblastoma. Although epilepsy was less
      frequent in high-grade glioma, in these patients seizures were more difficult to
      control. Poor seizure control was associated with motor and sensitive focal
      seizures and presence of neurological deficit. Patients without epilepsy and not
      taking AEDs never developed seizures during the follow-up. DISCUSSION: Our study
      clearly shows that epilepsy is more frequent in low-grade gliomas but seizures
      are more difficult to control in high-grade gliomas. In both cases seizures are a
      quite exclusive symptom at the onset that never appears during the stable course
      of the disease. Amongst glioblastoma multiforme (GBM), epilepsy is more frequent
      in GBM developing through progression from low-grade astrocitoma. Moreover, our
      study strongly indicates that the prophylactic use of AEDs in glioma is not
      justified.

PMID- 19183851
TI  - Epilepsy in glioblastoma multiforme: correlation with glutamine synthetase
      levels.
AB  - PURPOSE: The hypothesis addressed by this study is that a glutamine synthetase
      (GS) deficiency in neoplastic astrocytes is a possible molecular basis associated
      with seizure generation in glioblastoma multiforme (GBM). METHODS: Quantitative
      Western blot analysis of GS was performed in 20 individuals operated for
      malignant glioma. RESULTS: The levels of GS in patients with GBM and epilepsy
      were significantly lower (range 0.04-1.15; mean 0.35 +/- 0.36; median 0.25) than
      in non-epileptic GBM individuals (range 0.78-3.97; mean 1.64 +/- 0.99; median
      1.25; P = 0.002). No relationship has been found between histological features
      (i.e. necrosis, gliosis, stroma, inflammatory cells, giant cells, and
      haemosiderine) and GS expression or epilepsy. DISCUSSION: Even though the
      epileptogenesis in glioma is multifactorial, it is conceivable that a down
      regulation of GS may have an important pro-epileptogenic role in GBM, through the
      slowing of glutamate-glutamine cycle. This study suggests that seizures in GBM
      are coupled with a highly localized enzyme deficiency. The manipulation of GS
      activity might constitute a novel principle for inhibiting seizures in patients
      with glioma epilepsy.

PMID- 19183852
TI  - Coincidence of central neurocytoma and multiple glioblastomas: a rare case
      report.
AB  - Coincidence of parenchymal primary brain tumors of different histogenesis is
      extremely rare. To the best of our knowledge, the present case of simultaneous
      appearance of a central neurocytoma and multiple glioblastomas is the first to be
      reported. Multiple intraaxial brain neoplasms were disclosed in a 39-year-old man
      and were surgically resected. Histological diagnosis of the tumor located in the
      right lateral ventricle was central neurocytoma whereas two tumors of the left
      temporal lobe were glioblastomas. The latter were located in close proximity to
      the subarachnoid space, had atypical radiological appearance, and were slightly
      positive for synaptophysin and neurofilament protein. It can be speculated that
      both malignant neoplasms were, in fact, dedifferentiated central neurocytoma,
      which developed from distant tumor deposits. This case seems to be in agreement
      with the hypothesis that central neurocytoma arises from the progenitor cells
      with potential for both neuronal and glial differentiation. Better understanding
      of histogenesis of this tumor is definitely needed.

PMID- 19183853
TI  - Imaging biological activity of a glioblastoma treated with an individual patient
      tailored, experimental therapy regimen.
AB  - PURPOSE: To monitor the metabolic effects of an individual patient-tailored,
      experimental glioma therapy regimen that included repetitive multiple
      neurosurgical resections, radiosurgical interventions, and an adjuvant
      maintenance therapy based on the tyrosine kinase inhibitor imatinib in
      combination with the chemotherapeutic agent hydroxyurea (HU). PROCEDURES:
      Therapeutic effects were monitored in a 26-year-old male patient with a
      glioblastoma multiforme by multimodal imaging using sequential L: -[methyl-(11)C]
      methionine positron emission tomography (MET-PET) and MRI. The normalized MET
      uptake and volume of the metabolically active tumor were assessed sequentially.
      RESULTS: The individual patient-tailored, experimental glioma therapy caused a
      continuous decline of metabolically active tumor volume, associated with clinical
      remission over a period of more than two years. CONCLUSIONS: MET-PET seems to be
      useful for monitoring patient-tailored, experimental glioma therapy regimens,
      especially when patients are treated with a multi-step therapeutic regimen.
      Monitoring and guidance of those experimental therapy regimens by MET-PET in a
      larger patient group are needed to confirm its clinical value.

PMID- 19183854
TI  - Morphological changes in the retinal pigment epithelium on spectral-domain OCT in
      the unaffected eyes with idiopathic central serous chorioretinopathy.
AB  - PURPOSE: To report the changes seen in the retinal pigment epithelium (RPE)
      morphology in the asymptomatic eyes of patients with idiopathic central serous
      chorioretinopathy (ICSC) using spectral-domain Cirrus (TM) high-definition
      optical coherence tomography (HD-OCT). METHODS: In a prospective case series, 17
      consecutive patients with unilateral ICSC underwent spectral-domain Cirrus (TM)
      HD-OCT scans for both affected and opposite asymptomatic eye. Three-dimensional
      single-layer RPE map was studied in both eyes for morphological alterations, and
      findings were correlated with clinical presentation, fluorescein angiogram, and 5
      Line raster scan. Additionally, three-dimensional (3D) single-layer RPE maps done
      in 111 healthy volunteers served as control. RESULTS: In patients with ICSC, 3D
      single-layer RPE analysis of asymptomatic eyes showed presence of RPE bumps in 16
      (94%) eyes and pigment epithelium detachment (PED) in 2 (11.8%) eyes. The 5 Line
      raster scan was normal in all eyes. Of 222 normal (control) scans, 18 showed RPE
      bumps and none showed PED. Conclusions 3D single-layer RPE map showed abnormal
      pattern in the asymptomatic eyes of patients with unilateral ICSC. SUMMARY:
      Spectral-domain optical coherence tomography showed morphologic alterations in
      retinal pigment epithelium in both eyes of patients with idiopathic central
      serous chorioretinopathy.

PMID- 19183855
TI  - Clinical findings in unilateral acute idiopathic maculopathy: new findings in
      acute idiopathic maculopathy.
AB  - We report a case of unilateral acute idiopathic maculopathy (UAIM) with new
      clinical findings. A 34-year-old Japanese man had a neurosensory retinal
      detachment (approximately 5 disk diameters) with yellowish-white exudates at the
      macula in the left eye (visual acuity (VA) 0.4). Fluorescein angiography (FA)
      showed early hypofluorescent spots and late pooling in the subretinal space.
      Three weeks after onset, indocyanine green angiography (IA) showed numerous
      hypofluorescent spots at the lesion. Optical coherence tomography (OCT) showed
      subretinal fluids and an elevated choroidal lesion with low reflectivity,
      suggesting choroidal edema. The VA and fundus appearance spontaneously resolved
      without treatment three months after onset. The VA was 1.0 six months after
      onset. Irregular pigmentation remained at the macular lesion. The main UAIM
      pathology may be outer retinal layer and retinal pigment epithelial inflammation.
      FA, IA, and OCT suggested that choroidal inflammation may be involved in the
      pathogenesis of UAIM.

PMID- 19183856
TI  - Long-term control of choroidal neovascularization in quiescent congenital
      toxoplasma retinochoroiditis with photodynamic therapy: 4-year results.
AB  - PURPOSE: To evaluate the efficacy and safety of photodynamic therapy (PDT) in the
      long-term control of subfoveal choroidal neovascularization (CNV) associated with
      toxoplasmic retinochoroiditis. METHODS: The records of 13 patients with classic
      subfoveal CNV associated with toxoplasmic retinochoroiditis treated with PDT were
      reviewed. All patients were followed up for at least 48 months. Postoperative
      visual acuity was defined as a gain or loss of two or more lines of best
      corrected visual acuity (BCVA), respectively. Post-treatment CNV size was
      dichotomized into "increased" if the major CNV diameter (CMD) had increased by
      >or=300 microm, and as "stable/reduced" if it had decreased by >or=300 microm or
      had not changed by >300 microm. RESULTS: Nine patients [four males (44.4%) and
      five females (55.6%)] with a mean age of 20.1 +/- 4.3 years (range 14-27 years)
      were enrolled in the study. All had unilateral involvement. The median follow-up
      was 55 months (minimum 48, maximum 65 months). At the 48-month follow-up, all
      patients had stable/improved BCVA and a mean stable/reduced CMD (846 +/- 326.5
      microm), with the BCVA having improved significantly (p < 0.0001) from 0.29 +/-
      0.19 at baseline to 0.54 +/- 0.16 at 48 months. CONCLUSION: Photodynamic therapy
      seems to be a safe and effective approach to the long-term control of subfoveal
      CNV associated with toxoplasmic retinochoroiditis. Further trials are needed to
      validate these findings.

PMID- 19183857
TI  - Mapping QTLs for developmental traits in raspberry from bud break to ripe fruit.
AB  - Protected cropping systems have been adopted by the UK industry to improve fruit
      quality and extend the current season. Further manipulation of season, alongside
      consideration of climate change scenarios, requires an understanding of the
      processes controlling fruit ripening. Ripening stages were scored from May to
      July across different years and environments from a raspberry mapping population.
      Here the interest was in identifying QTLs for the overall ripening process as
      well as for the time to reach each stage, and principal coordinate analysis was
      used to summarise the ripening process. Linear interpolation was also used to
      estimate the time (in days) taken for each plot to reach each of the stages
      assessed. QTLs were identified across four chromosomes for ripening and the time
      to reach each stage. A MADS-box gene, Gene H and several raspberry ESTs were
      associated with the QTLs and markers associated with plant height have also been
      identified, paving the way for marker assisted selection in Rubus idaeus.

PMID- 19183858
TI  - Optimum contribution selection in large general tree breeding populations with an
      application to Scots pine.
AB  - Development of selection methods that optimises selection differential subject to
      a constraint on the increase of inbreeding (or coancestry) in a population is an
      important part of breeding programmes. One such method that has received much
      attention in animal breeding is the optimum contribution (OC) dynamic selection
      method. We implemented the OC algorithm and applied it to a diallel progeny trial
      of Pinus sylvestris L. (Scots pine) focussing on two traits (total tree height
      and stem diameter). The OC method resulted in a higher increase in genetic gain
      (8-30%) compared to the genetic gain achieved using standard restricted selection
      method at the same level of coancestry constraint. Genetic merit obtained at two
      different levels of restriction on coancestry showed that the benefit of OC was
      highest when restriction was strict. At the same level of genetic merit, OC
      decreased coancestry with 56 and 39% for diameter and height, respectively,
      compared to the level of coancestry obtained using unrestricted truncation
      selection. Inclusion of a dominance term in the statistical model resulted in
      changes in contribution rank of trees with 7 and 13% for diameter and height,
      respectively, compared to results achieved by using a pure additive model.
      However, the genetic gain was higher for the pure additive model than for the
      model including dominance for both traits.

PMID- 19183859
TI  - Pollen dispersal in sugar beet production fields.
AB  - Pollen-mediated gene flow has important implications for biodiversity
      conservation and for breeders and farmers' activities. In sugar beet production
      fields, a few sugar beet bolters can produce pollen as well as be fertilized by
      wild and weed beet. Since the crop, the wild beets, and the weed beets are the
      same species and intercross freely, the question of pollen flow is an important
      issue to determine the potential dispersal of transgenes from field to field and
      to wild habitats. We report here an experiment to describe pollen dispersal from
      a small herbicide-resistant sugar beet source towards male sterile target plants
      located along radiating lines up to 1,200 m away. Individual dispersal functions
      were inferred from statistical analyses and compared. Pollen limitation, as
      expected in root-production fields, was confirmed at all the distances from the
      pollen source. The number of resistant seeds produced by bait plants best fitted
      a fat-tailed probability distribution curve of pollen grains (power-law)
      dependent on the distance from the pollen source. A literature survey confirmed
      that power-law function could fit in most cases. The b coefficient was lower than
      2. The number of fertilized flowers by background (herbicide-susceptible) pollen
      grains was uniform across the whole field. Airborne pollen had a fertilization
      impact equivalent to that of one adjacent bolter. The individual dispersal
      function from different pollen sources can be integrated to provide the pollen
      cloud composition for a given target plant, thus allowing modeling of gene flow
      in a field, inter-fields in a small region, and also in seed-production area.
      Long-distance pollen flow is not negligible and could play an important role in
      rapid transgene dispersal from crop to wild and weed beets in the landscape. The
      removing of any bolting, herbicide-resistant sugar beet should be compulsory to
      prevent the occurrence of herbicide-resistant weed beet, thus preventing gene
      flow to wild populations and preserving the sustainable utility of the resistant
      varieties. Whether such a goal is attainable remains an open question and
      certainly would be worth a large scale experimental study.

PMID- 19183860
TI  - The identification of candidate genes associated with Pch2 eyespot resistance in
      wheat using cDNA-AFLP.
AB  - Eyespot is a fungal disease of the stem base of cereal crops and causes lodging
      and the premature ripening of grain. Wheat cultivar Cappelle Desprez contains a
      highly durable eyespot resistance gene, Pch2 on the long arm of chromosome 7A. A
      cDNA-amplified fragment length polymorphism (AFLP) platform was used to identify
      genes differentially expressed between the eyespot susceptible variety Chinese
      Spring (CS) and the CS chromosome substitution line Cappelle Desprez 7A (CS/CD7A)
      which contains Pch2. Induced and constitutive gene expression was examined to
      compare differences between non-infected and plants infected with Oculimacula
      acuformis. Only 34 of approximately 4,700 cDNA-AFLP fragments were differentially
      expressed between CS and CS/CD7A. Clones were obtained for 29 fragments, of which
      four had homology to proteins involved with plant defence responses. Fourteen
      clones mapped to chromosome 7A and three of these mapped in the region of Pch2
      making them putative candidates for involvement in eyespot resistance. Of
      particular importance are two fragments; 4CD7A8 and 19CD7A4, which have homology
      to an Oryza sativa putative callose synthase protein and a putative cereal cyst
      nematode NBS-LRR disease resistance protein (RCCN) respectively. Differential
      expression associated with Pch2 was examined by semi-quantitative RT-PCR. Of
      those genes tested, only four were differentially expressed at 14 days post
      inoculation. We therefore suggest that a majority of the differences in the cDNA
      AFLP profiles are due to allelic polymorphisms between CS and CD alleles rather
      than differences in expression.

PMID- 19183862
TI  - QTL detection in maize testcross progenies as affected by related and unrelated
      testers.
AB  - The evaluation of recombinant inbred lines (RILs) per se can be biased by
      inbreeding depression in case of allogamous species. To overcome this drawback,
      RILs can be evaluated in combination with testers; however, testers can carry
      dominant alleles at the quantitative trait loci (QTL), thus hampering their
      detection. This study was conducted on the maize (Zea mays L.) population of 142
      RILs derived from the single cross B73 x H99 to evaluate the role of different
      testers in affecting: (1) QTL detection, (2) the estimates of their effects, and
      (3) the consistency of such estimates across testers. Testcrosses (TCs) were
      produced by crossing RILs with inbred testers B73 [TC(B)], H99 [TC(H)], and Mo17
      [TC(M)]. TCs were field tested in three environments. TC(B) mean was higher than
      TC(H) mean for all traits, while TC(M) mean was the highest for plant vigor
      traits and grain yield. As to the number of detected QTL, tester Mo17 was
      superior to H99 and B73 for traits with prevailing additive effects. Several
      overlaps among the QTL were detected in two or all the three TC populations with
      QTL effects being almost always consistent (same sign). For traits with
      prevailing dominance-overdominance effects, as grain yield, the poor performing
      tester H99 was clearly the most effective; fewer overlaps were found and some of
      them were inconsistent (different sign). Epistatic interactions were of minor
      importance. In conclusion, the three testers proved to affect QTL detection and
      estimation of their effects, especially for traits showing high dominance levels.

PMID- 19183861
TI  - Genetic and physical mapping of new EST-derived SSRs on the A and B genome
      chromosomes of wheat.
AB  - The availability of genetic maps and phenotypic data of segregating populations
      allows to localize and map agronomically important genes, and to identify closely
      associated molecular markers to be used in marker-assisted selection and
      positional cloning. The objective of the present work was to develop a durum
      wheat intervarietal genetic and physical map based on genomic microsatellite or
      genomic simple sequence repeats (gSSR) markers and expressed sequence tag (EST)
      derived microsatellite (EST-SSR) markers. A set of 122 new EST-SSR loci amplified
      by 100 primer pairs was genetically mapped on the wheat A and B genome
      chromosomes. The whole map also comprises 149 gSSR markers amplified by 120
      primer pairs used as anchor chromosome loci, two morphological markers (Black
      colour, Bla1, and spike glaucousness, Ws) and two seed storage protein loci (Gli
      A2 and Gli-B2). The majority of SSR markers tested (182) was chromosome-specific.
      Out of 275 loci 241 loci assembled in 25 linkage groups assigned to the
      chromosomes of the A and B genome and 34 remained unlinked. A higher percentage
      of markers (54.4%), localized on the B genome chromosomes, in comparison to 45.6%
      distributed on the A genome. The whole map covered 1,605 cM. The B genome
      accounted for 852.2 cM of genetic distance; the A genome basic map spanned 753.1
      cM with a minimum length of 46.6 cM for chromosome 5A and a maximum of 156.2 cM
      for chromosome 3A and an average value of 114.5 cM. The primer sets that
      amplified two or more loci mapped to homoeologous as well as to non-homoeologous
      sites. Out of 241 genetically mapped loci 213 (88.4%) were physically mapped by
      using the nulli-tetrasomic, ditelosomic and a stock of 58 deletion lines dividing
      the A and B genome chromosomes in 94 bins. No discrepancies concerning marker
      order were observed but the cytogenetic maps revealed in some cases small genetic
      distance covered large physical regions. Putative function for mapped SSRs were
      assigned by searching against GenBank nonredundant database using TBLASTX
      algorithms.

PMID- 19183864
TI  - Activation of the heat shock response in a primary cellular model of motoneuron
      neurodegeneration-evidence for neuroprotective and neurotoxic effects.
AB  - Pharmacological up-regulation of heat shock proteins (hsps) rescues motoneurons
      from cell death in a mouse model of amyotrophic lateral sclerosis. However, the
      relationship between increased hsp expression and neuronal survival is not
      straightforward. Here we examined the effects of two pharmacological agents that
      induce the heat shock response via activation of HSF-1, on stressed primary
      motoneurons in culture. Although both arimoclomol and celastrol induced the
      expression of Hsp70, their effects on primary motoneurons in culture were
      significantly different. Whereas arimoclomol had survival-promoting effects,
      rescuing motoneurons from staurosporin and H(2)O(2) induced apoptosis, celastrol
      not only failed to protect stressed motoneurons from apoptosis under same
      experimental conditions, but was neurotoxic and induced neuronal death.
      Immunostaining of celastrol-treated cultures for hsp70 and activated caspase-3
      revealed that celastrol treatment activates both the heat shock response and the
      apoptotic cell death cascade. These results indicate that not all agents that
      activate the heat shock response will necessarily be neuroprotective.

PMID- 19183865
TI  - The knockdown of c-myc expression by RNAi inhibits cell proliferation in human
      colon cancer HT-29 cells in vitro and in vivo.
AB  - We investigated the effects of RNA interference-mediated silencing of the c-myc
      gene on celluar proliferation and apoptosis in human colon cancer HT-29 cells in
      vitro and in vivo. A small interfering RNA (siRNA) targeting c-myc was designed,
      the DNA template was synthesized, and the siRNA was obtained by in vitro
      transcription. After siRNA transfection into HT-29 and human neuroblastoma IMR-32
      cells with Lipofectamine 2000, the proliferation of the HT-29 and IMR-32 cells
      was assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide
      (MTT) colorimetry, and Hoechst 33258 staining was used to observe cell apoptosis.
      Following gene transfer to HT-29 cells, the expression of c-myc mRNA was examined
      via reverse transcription polymerase chain reaction, and the level of the protein
      via Western blot assay. Growth curves were constructed and in vivo experiments
      were performed on nude mice to assess the effects of c-myc silencing on tumor
      growth. The c-myc expression in the tumor tissue was measured by reverse
      transcription polymerase chain reaction and subsequently by immunohistochemistry.
      Our paper demonstrates that the delivery of siRNA directed against c-myc not only
      efficiently down-regulated the expression of c-myc, inhibited the proliferation
      of HT-29 cells and induced apoptosis in vitro, but also suppressed the growth of
      colon cancer cells in vivo.

PMID- 19183867
TI  - The effect of severe zinc deficiency and zinc supplement on spatial learning and
      memory.
AB  - Zinc deficiency during pregnancy and during lactation has been shown to impair
      cognitive function and motor activity in offspring rats. In the present study,
      the effect of zinc deficiency and zinc supplement on spatial learning and memory
      in Morris Water Maze (MWM) and motor activity in open field were investigated.
      Pregnant rats after mating were divided to three groups. Control group fed a
      standard diet and a zinc deficient (ZnD) group fed a diet deficient in zinc (0.5
      1.5 ppm) and a zinc supplement (ZnS) group fed a standard diet and enhanced zinc
      in the drinking water (10 ppm). All the diets were exposed during the last
      trisemester of pregnancy and during lactation. Rat's offspring in these groups
      were tested for spatial learning and memory in MWM at post natal day (PND) 56 and
      were tested for motor activity in open field at PND 66.The Escape Latency (EL)
      and Traveled Distance (TD) in the ZnD group were increased but Percentage of Time
      Spent in the target quadrant (PTS) was decreased compared to the control group.
      In addition, these were no significant differences in EL and TD, but PTS had
      significant increase in ZnS compared to the control group. In the open field,
      Total Distance Moved (TDM) and Time of Motor Activity (TMA) for the ZnD were
      decreased compared to the control group, but there were no significant
      differences in TDM and TMA between control and ZnS groups. These findings suggest
      that zinc deficiency during the last trimester of pregnancy and during lactation
      impaired spatial learning and memory in their offsprings and has also negative
      effect on motor activity. In addition, ZnS has a significant effect on spatial
      learning and memory but no effect on motor activity in their offsprings.

PMID- 19183866
TI  - The role of the antioxidant enzymes in erythrocytes in the development of
      arterial hypertension among humans exposed to lead.
AB  - The study population included employees of metal works, with significant exposure
      to lead (Pb) for about 20 years (mean blood lead level PbB = 43 microg/dl),
      divided into four groups: normotensive (Pb-normotensive), high-normotensive,
      first (HT-1), and second degree (HT-2) of hypertension. The control group
      comprised of 30 office workers with normal blood pressure and no history of
      occupational exposure to lead. In erythrocytes, the activity of antioxidant
      enzymes and lipid peroxidation (measured as concentration of malondialdehyde
      (MDA)) was estimated. MDA concentration, glutathione peroxide (GPx), and
      superoxide dimutase (SOD) activities were significantly higher in Pb-normotensive
      group when compared to the normotensive control. Body mass index, age, duration
      of exposure to lead, and PbB were higher in both hypertensive groups than in Pb
      normotensive or high-normotensive groups. MDA increased in HT-1 group by 48% and
      in HT-2 by 72%, and the activity of GPx decreased significantly in HT-1 group, by
      30% and in HT-2 by 43%. No significant differences were observed in their
      activity of SOD, catalase, and glutathione reductase in erythrocytes. Arterial
      blood pressure (both systolic and diastolic) positively correlated with body mass
      index (BMI), age, lead exposure duration, PbB, MDA, and negatively correlated
      with GPx. There was no significant correlation between BMI and MDA, BMI and GPx,
      age and MDA, AND age and GPx. IN CONCLUSION: (1) lead increases erythrocyte MDA
      concentration and the activity of GPx as well as SOD in normotensive subjects.
      (2) Among individuals exposed to lead, with arterial hypertension diagnosed,
      higher body mass index, age, values of blood lead level, and prolonged exposure
      to lead have been noticed, accompanied by intensified oxidative stress and the
      decrease in the activity of glutathione peroxidase in erythrocytes. The reasons
      for increase of blood pressure in lead exposure remain unrecognized.

PMID- 19183868
TI  - Effect of soluble fiber pectin on growth and intestinal iron absorption in rats
      during recovery from iron deficiency anemia.
AB  - The objective of this study was to verify whether soluble fiber pectin interferes
      in growth and intestinal iron absorption in rats during iron deficiency anemia
      recovery. Twenty-one-day-old Wistar rats (n = 48) were fed for 2 weeks on a diet
      without iron in order to induce iron deficiency anemia. The anemic animals (age =
      36 days) were divided into two groups: (1) pectin, 50 g of pectin per kilogram of
      diet, and (2) control, diet without dietary fiber. Iron was added to the diets
      for the two groups in order to reverse the anemia. During the iron deficiency
      anemia recovery phase (3 weeks), the pectin group showed lower mean values (p <
      0.05) of weekly food intake (89.18 +/- 10.82; 107.60 +/- 11.70; 114.50 +/- 16.29
      g, respectively, for the pectin group and 99.56 +/- 10.60; 116.36 +/- 15.33;
      125.66 +/- 17.25 g, respectively, for the control group). The body weight of the
      pectin group was lower (p < 0.05) during the study's second and third weeks
      (192.42 +/- 16.67 and 228.75 +/- 19.81 g, respectively, and 202.87 +/- 19.96 and
      243.51 +/- 20.44 g for the control group). Pectin led to a reduction in food
      intake and growth but not to iron absorption when taking into account the
      regeneration of hemoglobin mass.

PMID- 19183869
TI  - Copper and ceruloplasmin in children undergoing heart surgery with
      cardiopulmonary bypass.
AB  - Heart surgery with cardiopulmonary bypass (CPB) nowadays has become a routine
      procedure. However, under nonadequate hemodynamic conditions and because of the
      changes related to ischemia-reperfusion, there is a possibility to provoke
      oxidative stress with all undesirable consequences. Copper (Cu) is closely
      related to this stress, taking part in the formation of the hazardous-free
      radicals. Meanwhile, at least in the pediatric area, little is known about Cu
      kinetics during cardiac surgery. The purpose of the present work was to study Cu
      and ceruloplasmin (Cp) dynamics during surgery with CPB in children. Twenty-one
      patients of both genders from Campo Grande, Brazil with congenital heart
      conditions were enrolled in the investigation. Blood samples were collected
      before the surgery and during and 24 h after it. Cu and Cp levels were measured
      at selected moments and the influence of hemodilution studied. It was concluded
      that serum Cu dynamics during cardiopulmonary bypass reflects the protective
      effects of this trace element. Ceruloplasmin levels correlate positively with
      copper.

PMID- 19183870
TI  - Aporphine alkaloids from Clematis parviloba and their antifungal activity.
AB  - A new aporphine alkaloid, beta-magnoflorine (1), together with a known aporphine
      alkaloid, alpha-magnoflorine (2), were isolated from the aerial parts of Clematis
      parviloba. Their structures were elucidated on the basis of comprehensive
      spectroscopic techniques. In addition, both compounds showed potent antifungal
      activities against Penicillium avellaneum UC-4376.

PMID- 19183871
TI  - Anti-inflammatory phenylpropanoid glycosides from Clerodendron trichotomum
      leaves.
AB  - The chromatographic separation of MeOH extract from Clerodendron trichotomum
      Thunberg leaves led to the isolation of three phenylpropanoid compounds. Using
      spectroscopic methods, the structures of these compounds were determined as beta
      (3', 4'-dihydroxyphenyl)ethyl-O-alpha-L-rhamnopyranosyl (1-->3)-beta-D-(4-O
      caffeoyl)-glucopyranoside, acteoside (verbascoside) (1), beta-(3', 4'
      dihydroxyphenyl)ethyl-O-alpha-L-rhamnopyranosyl (1-->3)-beta-D-(6-O-caffeoyl)
      glucopyranoside, isoacteoside (2), beta-(3', 4'-dihydroxyphenyl) ethyl-O-alpha-L
      rhamnopyranosyl (1-->3)-beta-D-glucopyranoside, and decaffeoylacteoside (3). We
      measured the anti-inflammatory activity of these three phenylpropanoid compounds
      both in vitro (DPPH reduction assay, TBARS assay on Cu (2+)-induced oxidized LDL,
      PGE(2) assay) and in vivo (acetic acid induced vascular permeability in mice and
      carrageenan-induced hind paw edema in rats). 80% methanol fraction and acteoside
      had the activity.

PMID- 19183872
TI  - Structure-activity relationship studies of novel oxygen-incorporated SAHA
      analogues.
AB  - Novel oxygen-incorporated SAHA (oxa-SAHA) analogues, in which oxygen was inserted
      in the alkyl linker connecting the hydroxamic acid moiety and amide group, were
      synthesized and their inhibitory activities on histone deacetylase were
      evaluated. The most active oxa-SAHA analogue potently inhibited histone
      deacetylase, almost as potently as SAHA. Various structural modifications in the
      amide, but not the hydroxamic acid, significantly affected the inhibitory
      activities of the derivatives. Based on the inhibitory data, the N-phenyl moiety
      of the amide turned to be a better modification site for enhancing the inhibitory
      activity.

PMID- 19183873
TI  - Synthesis of 2-substituted-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles as potential
      anticonvulsant agents.
AB  - A series of 2-substituted-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles were
      synthesized. The anticonvulsant effect and neurotoxicity of the compounds
      (intraperitoneally) were evaluated with the maximal electroshock (MES) test,
      subcutaneous pentylenetetrazole (sc-PTZ), and rotarod tests in mice. 2-Phenyl-6
      (4H-1,2,4-triazol-4-yl)benzo[d]oxazole (3g) was the most active and also had the
      lowest toxicity. In the anti-MES potency test, it showed median effective dose
      (ED(50)) of 29.5 mg/kg, a median toxicity dose (TD(50)) of 285 mg/kg, and a
      protective index (PI) of 9.7, which is greater than the reference drug,
      carbamazepine, which has a PI of 6.4.

PMID- 19183874
TI  - Synthesis and antimicrobial activity of 1-benzhydryl-sulfonyl-4-(3-(piperidin-4
      yl) propyl)piperidine derivatives against pathogens of Lycopersicon esculentum: a
      structure-activity evaluation study.
AB  - Several 1-benzhydryl-sulfonyl-4-(3-(piperidin-4-yl)propyl)piperidine derivatives
      8(a-j) were prepared by the treatment of substituted benzhydryl chlorides with 4
      (3-(piperidin-4-yl)propyl)piperidine followed by N-sulfonation with sulfonyl
      chlorides in the presence of dry methylene dichloride and triethyl amine. The
      synthesized compounds were characterized by (1)H-NMR, IR, and elemental analysis.
      All the synthesized compounds were evaluated in vitro for their efficacy as
      antimicrobial agents by artificial inoculation technique against standard strains
      of two important bacterial viz., Xanthomonas axonopodis pv. vesicatoria and
      Ralstonia solanacearum as well as and two fungal pathogens namely Alternaria
      solani and Fusarium solani of tomato plants. We have briefly investigated the
      structure-activity relation studies and reveal that the nature of substitutions
      on benzhydryl ring and sulfonamide ring influences the antibacterial activity.
      Among the synthesized new compounds 8b, 8d, 8g, 8h, 8i, and 8j were showed
      significant potent antimicrobial activities compared to the standard drugs
      chloramphenicol, mancozeb.

PMID- 19183875
TI  - Diacylglycerol acyltransferase-inhibitory compounds from Erythrina senegalensis.
AB  - Inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT) is proposed to be a
      drug target for the treatment of obesity and type 2 diabetes. Bioassay-guided
      fractionation of the CH(2)Cl(2)-soluble extract of the stem bark of Erythrina
      senegalensis, using an in vitro DGAT enzyme assay, resulted in the isolation of
      eight known prenylflavonoids, 8-prenylleutone (1), auriculatin (2),
      erysenegalensein O (3), erysenegalensein D (4), erysenegalensein N (5), derrone
      (6), alpinumisoflavone (7), and 6,8-diprenylgenistein (8). Compounds 1, 2-4, 6,
      and 8 inhibited DGAT activity, with IC(50) values ranging from 1.1 +/- 0.3 to
      15.1 +/- 1.1 microg/mL. On the basis of the data obtained, we propose
      isoflavonoids with isoprenyl groups as a novel class of DGAT inhibitors.

PMID- 19183876
TI  - Anti-androgen-independent prostate cancer effects of ginsenoside metabolites in
      vitro: mechanism and possible structure-activity relationship investigation.
AB  - Treatment of androgen-independent prostate cancer (AIPC) remains unsatisfactory.
      In our present experiment, natural occurring ginsenosides (NOGs) and intestinal
      bacterial metabolites (IBMs) were employed to investigate their anti-AIPC cell
      growth activity using PC-3 cells. Our results showed that the IBMs exerted more
      portent anti-AIPC activity than NOGs, by decreasing survival rate, inhibiting
      proliferation, inducing apoptosis, and leading to cell cycle arrest in AIPC PC-3
      cells. The increase of LogP and decrease of C-6 steric hindrance, which were
      caused by deglycosylation by intestinal bacteria, may be the reason for the
      higher anti-AIPC activity of IBMs.

PMID- 19183877
TI  - Synthesis and cytotoxic activities of C-benzylated flavonoids.
AB  - Some C-benzylated flavonoids based on gericudranin A were synthesized and
      evaluated their cytotoxic activities for the elucidation of structure-activity
      relationship. 2,4,6-Trihydroxyacetophenone was converted to target molecules in 6
      approximately 7 steps via sequential protection, aldol condensation, cyclization,
      regioselective C-benzylation, and deprotection. The cellular growth inhibition of
      the synthetic C-benzylated flavonoids was investigated against sixteen human
      cancer cell lines. Among these compounds, 5b showed the most potent
      cytotoxicities against several cell lines, especially as potent as adriamycin
      against SNB19 cell lines with an IC(50) value of 0.7 microM.

PMID- 19183879
TI  - In vitro anti-inflammatory activity of carvacrol: Inhibitory effect on COX-2
      catalyzed prostaglandin E(2) biosynthesis.
AB  - Possible anti-inflammatory effect of carvacrol was evaluated by in vitro
      cyclooxygenase-2 (COX-2) assay. Carvacrol inhibited production of prostaglandin
      E(2) catalysed by COX-2 with an IC(50) value of 0.8 microM what is practically
      the same concentration as the IC(50) obtained for the standard inhibitors
      indomethacin and NS-398 with values of 0.7 microM and 0.8 microM, respectively.
      The COX-1 was inhibited approximately at the same rate (IC(50) of 0.7 microM for
      carvacrol), which suggests non-selective inhibition of both enzyme isoforms. The
      results of the study demonstrate possible anti-inflammatory potential of this
      compound due to the inhibition of inducible COX-2 isoform.

PMID- 19183878
TI  - The inhibitory effects of cholalic acid and hyodeoxycholalic acid on the
      expression of TNFalpha and IL-1beta after cerebral ischemia in rats.
AB  - Previous studies have shown that Qing Kai Ling, a traditional Chinese medicine,
      was able to effectively prevent the inflammation from cerebral ischemia (Chen et
      al., 2002). The cholalic acid and hyodeoxycholalic acid (cholalic acid mixture)
      was major active components in Qing Kai Ling. To study the effects of cholalic
      acid mixture on the damage cascade of cerebral ischemia, rat model of focal
      cerebral ischemia was established by permanent occlusion of left middle cerebral
      artery. We found that the administration of cholalic acid mixture could reduce
      the ischemic infarct size after 24 h of ischemia, and cholalic acid mixture could
      be detected in cerebrospinal fluid after 2h of administration. We also found that
      the concentrations of tumor necrosis factor-alpha and interlukin-1beta in rat
      brain were significantly lower when compared to the untreated animals after 12 h
      and 24 h of ischemia. The concentrations of von Willebrand factor and neuron
      specific enolase in the plasma were remarkably decreased in cholalic acid mixture
      treated animals than in the untreated ones after 12h of ischemia. Our results
      suggested that cholalic acid mixture is able to decrease the expression of
      inflammation factors including tumor necrosis factor-alpha and interlukin-1beta
      after focal cerebral ischemia.

PMID- 19183880
TI  - YL-I-108, a synthetic chalcone derivative, inhibits lipopolysaccharide-stimulated
      nitric oxide production in RAW 264.7 murine macrophages: involvement of heme
      oxygenase-1 induction and blockade of activator protein-1.
AB  - Chalcones, a group of phenolic compounds, exhibit potent anti-inflammatory
      properties. In the present study, we synthesized chalcone derivative, YL-I-108
      ((E)-1-(2-methoxy-4,6-bis(methoxymethoxy)phenyl)-3-(3-nitrophenyl)prop-2-en-1
      one), and examined its effect on the production of pro-inflammatory mediators.
      Treatment of RAW 264.7 macrophages with YL-I-108 potently inhibited nitrite
      production stimulated by LPS. YL-I-108 treatment also markedly inhibited
      expressions of inducible nitric oxide synthase (iNOS) and tumor necrosis factor
      alpha (TNF-alpha). Treatment of cells with YL-I-108 significantly inhibited LPS
      stimulated activator protein-1 (AP-1)-dependent reporter gene expression, whereas
      nuclear factor-kappaB (NF-kappaB) activity was not affected, indicating that down
      regulation of iNOS expression by YL-I-108 is attributed by blockade of AP-1. In
      addition, YL-I-108 treatment led to an increase in heme oxygenase-1 (HO-1) mRNA
      and protein expression, accompanied with the increased expression of nuclear
      factor-erythroid 2-related factor 2 (Nrf2). Treatment with SnPP, a selective HO-1
      inhibitor, reversed YL-I-108-mediated suppression of nitrite production,
      suggesting that HO-1 induction is implicated in the suppression of NO production
      by YL-I-108. In contrast, SnPP treatment did not reverse YL-I-108-mediated
      suppression of AP-1 activation, suggesting that AP-1 inhibition by YL-I-108 is
      independent of HO-1 induction. Together, these results indicate that YL-I-108
      suppresses NO production in LPS-stimulated macrophages via simultaneous induction
      of HO-1 expression and blockade of AP-1 activation.

PMID- 19183881
TI  - Inhibitory effects of an aqueous extract of Cornus kousa Burg. leaves on TNF
      alpha-induced chemokine expression and monocyte adhesion to human colonic
      epithelial cells.
AB  - An aqueous extract of Cornus kousa Burg. leaves (ACK) that contained high amount
      of polyphenols showed significant antioxidant activity against
      diphenylpicrylhydrazyl (DPPH) radicals and TNF-alpha-generated reactive oxygen
      species. ACK at concentrations of 10 and 50 microg/mL significantly inhibited TNF
      alpha-induced adhesion of U937 pre-monocytic cells to HT-29 colon epithelial
      cells in a concentration-dependent manner. The reduced adhesion by ACK correlated
      with the suppressed expressions of monocyte chemoattractant protein (MCP)-1 and
      interleukin (IL)-8, the major inflammatory bowel disease (IBD)-associated
      chemokines. Moreover, ACK significantly suppressed TNF-alpha-induced
      translocation of redox-sensitive nuclear factor (NF)-kappaB as well as
      degradation of cytosolic I-kappaBalpha. The effective concentrations of ACK were
      much lower than that of 5-aminosalicylic acid (3.06 mg/mL), which is an active
      metabolite of sulfasalazine, a well-known drug used in the treatment of IBD. The
      results indicate that ACK may provide a potential benefit for the prevention and
      treatment of inflammatory diseases such as IBD.

PMID- 19183882
TI  - NS398 protects cells from sodium nitroprusside-mediated cytotoxicity through
      enhancing HO-1 induction independent of COX-2 inhibition.
AB  - Heme oxygenase-1 (HO-1) plays a preventive role in oxidative stress. In contrast,
      COX-2 is involved in the pathogenesis of many inflammatory diseases, thus COX-2
      inhibitor is believed to exert anti-inflammatory properties by blocking COX-2.
      Recently, however, salicylate the active metabolite of aspirin showed COX
      independent anti-inflammatory effects through induction of HO-1. Thus, we
      hypothesized that HO-1 are induced as an adaptive response to sodium
      nitroprusside (SNP) and play a protective role against cytotoxicity. Moreover, we
      investigated the protective effect of NS398 known as a selective COX-2 inhibitor
      on SNP-mediated cytotoxicity, and whether the protective effect of NS398 is due
      to COX-2 inhibition or not. SNP induced cytotoxicity in a dose-dependent manner,
      which was enhanced by inhibition of HO-1, suggesting that HO-1 acts in an
      adaptive response to SNP. Interestingly, NS398 decreased SNP-mediated
      cytotoxicity whereas COX-2 siRNA did not. Furthermore, NS398 enhanced SNP-induced
      HO-1 induction even though NS398 alone failed to induce HO-1 protein expression.
      In addition, NS398 enhanced SNP-induced COX-2, even though NS398 effectively
      inhibited SNP-mediated PGE(2) production. These results demonstrate that NS398
      exerts cytoprotective effects by inducing HO-1 independent of COX-2 inhibition.

PMID- 19183884
TI  - Biological characterization of long-term cultured human mesenchymal stem cells.
AB  - Human mesenchymal stem cells (hMSCs) have generated a great deal of interest in
      clinical applications. The reason is that they may have the plasticity needed to
      differentiate into multiple lineages and the ability to expand ex vivo. For the
      therapeutic applications of hMSCs to be of practical use, it is crucial to assess
      the efficacy and safety of hMSCs in long-term ex vivo expansion. In this study,
      we cultured hMSCs by population doubling (PD) 60, and investigated their growth,
      osteogenic and adipogenic differential abilities, change of surface markers,
      telomerase activity, telomere length, and gene expression related to
      tumorigenesis. An in vivo tumorigenesis assay was also carried out. In long-term
      expanded hMSCs, the cells became aged above PD 30 and their adipogenic and
      osteogenic differentiation potential decreased. Telomerase activity unchanged
      whereas telomere length decreased and karyotypes were not changed. Gene
      expressions related to tumorigenesis decreased in proportion as the PD of hMSCs
      increased. In vivo transplantation of long-term cultured hMSCs to nude mice did
      not result in tumor formation. These findings suggest that diverse tests for
      cellular therapy should be considered during the ex vivo culture of hMSCs,
      particularly when a prolonged and extended propagation period is required.

PMID- 19183883
TI  - Protection against amyloid beta cytotoxicity by sulforaphane: role of the
      proteasome.
AB  - The 26S proteasome plays a major role in degradation of abnormal proteins within
      the cell. The indirect antioxidant including sulforaphane (SFN) protects cells
      from oxidative damage by increasing the expression of Nrf2-target genes. It has
      been observed that the expression of multiple subunits of the proteasome was up
      regulated by indirect antioxidants through the Nrf2 pathway. In the current
      study, the role of SFN in amyloid beta(1-42) (Abeta(1-42))-induced cytotoxicity
      has been investigated in murine neuroblastoma cells. Treatment with SFN protected
      cells from Abeta(1-42)-mediated cell death in Neuro2A and N1E 115 cells.
      Inhibition of proteasome activities by MG132 could abolish the protective effect
      of SFN against Abeta(1-42). Neuro2A cells, which were stably overexpressing the
      catalytic subunit of the proteasome PSMB5, showed an elevated resistance toward
      Abeta(1-42) toxicity compared to control cells. Furthermore, the in vitro assay
      demonstrated that the Abeta(1-42) peptide is degraded by the proteasome fraction.
      These results suggest that proteasome-inducing indirect antioxidants may
      facilitate the removal of the Abeta(1-42) peptide and lead to the amelioration of
      abnormal protein-associated etiologies.

PMID- 19183885
TI  - Development of nifedipine-loaded coated gelatin microcapsule as a long acting
      oral delivery.
AB  - To develop the long acting nifedipine oral delivery with enhanced
      bioavailability, nifedipine-loaded gelatin microcapsule containing nifedipine and
      ethanol in gelatin shell was prepared using a spray-dryer, and then coated
      microcapsule was prepared by coating the gelatin microcapsule with Eudragit
      acrylic resin. The dissolution test and the bioavailability of the coated
      microcapsule in rats were evaluated compared to nifedipine powder. The amount of
      nifedipine dissolved from gelatin microcapsule for 30 min increased about 5-fold
      compared to nifedipine powder in pH 1.2 simulated gastric fluid. Nifedipine
      released from the coated microcapsule was retarded in pH 1.2 simulated gastric
      fluid compared with that from gelatin microcapsule. Furthermore, the coated
      gelatin microcapsule maintained the plasma level of nifedipine over 4 h and gave
      significantly higher AUC of nifedipine than nifedipine powder. Thus, the Eudragit
      coated gelatin microcapsule, which could maintain the plasma level of nifedipine
      over a longer period without the initial burst-out plasma concentration, is a
      preferable delivery system for poorly water-soluble nifedipine.

PMID- 19183886
TI  - Enhanced bioavailability of etoposide after oral or intravenous administration of
      etoposide with kaempferol in rats.
AB  - This study was to investigate the effect of kaempferol on the pharmacokinetics of
      etoposide after oral or intravenous administration of etoposide in rats. The oral
      (6 mg/kg) or intravenous (2 mg/kg) etoposide was administered to rats alone or 30
      min after the oral kaempferol (1, 4, or 12 mg/kg) administration. Compared to the
      oral control group, the presence of kaempferol significantly (4 mg/kg, P < 0.05;
      12 mg/kg, P < 0.01) increased the area under the plasma concentrationtime curve
      (AUC) and the peak concentration (C(max)) of the oral etoposide. Kaempferol
      decreased significantly (4 or 12 mg/kg, P < 0.05) the total body clearance (CL/F)
      of oral etoposide, while there was no significant change in the terminal halflife
      (t(1/2)), the elimination rate constant (K(el)) and the time to reach the peak
      concentration (T(max)) of etoposide in the presense of kaempferol. Consequently,
      the absolute bioavailability (AB%) of oral etoposide with kaempferol was
      significantly higher (4 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) than those from the
      control group. Compared to the intravenous control group, the presence of
      kaempferol enhanced the AUC of intravenously administered etoposide, however,
      only presence of 12 mg/kg of kaempferol significant (P < 0.05) increased AUC of
      etoposide. The enhanced bioavailability of oral etoposide by kaempferol could
      have been due to an inhibition of cytochrom P450 (CYP) 3A and P-glycoprotein (P
      gp) in the intestinal or decreased total body clearance in the liver by
      kaempferol. The dosage regimen of etoposide should be taken into consideration
      for potential drug interaction when combined with kaempferol or dietary
      supplements containing kaempferol in patients.

PMID- 19183887
TI  - Toxicity studies of cremophor-free paclitaxel solid dispersion formulated by a
      supercritical antisolvent process.
AB  - To evaluate the acute toxicity of a paclitaxel solid dispersion formulation,
      single dose studies in ICR mice were carried out for injectable excipients,
      paclitaxel solid dispersion powder, and Taxol. In the dose range of excipients
      used for preparing paclitaxel solid dispersion, each excipient was clinically
      safe, and the LD(50) for exicipients was higher than 2,000 mg/kg for both males
      and females. In this study, there were no remarkable clinical signs or deaths
      related to paclitaxel solid dispersion even at doses up to 160 mg/kg of
      paclitaxel. But Taxol resulted in clinical signs when it contained more than 30
      mg/mL paclitaxel. The LD(50) for paclitaxel solid dispersion was above 160 mg/kg
      and the LD(50) for Taxol was 31.3 mg/kg, more than 5 times lower than that of
      paclitaxel solid dispersion. However, paclitaxel solid dispersion could not be
      administered i.v. at a dose exceeding 160 mg/kg, because of high viscosity. To
      evaluate the nephrotoxicity of paclitaxel solid dispersion, plasma level of
      creatinine and kidney weight were measured and compared to Taxol. At the doses
      administered, paclitaxel solid dispersion did not change creatinine clearance,
      while Taxol killed all animals at doses >15 mg/kg. To investigate membrane damage
      when paclitaxel formulations were injected, hemolytic activity was determined for
      different concentrations. Paclitaxel solid dispersion showed about 10% hemolytic
      activity, whereas Taxol showed about 40% hemolytic activity when it contained 2
      mg of paclitaxel. Comparisons with the LD(50) value, nephrotoxicity, and
      hemolytic activity of Taxol suggested that Cremophor-free paclitaxel solid
      dispersion as an injectable formulation is a promising approach to increasing the
      safety and clinical efficacy of paclitaxel for treatment of cancer.

PMID- 19183888
TI  - Pharmacokinetics of (-)-epicatechin in rabbits.
AB  - The aim of this study was to investigate the pharmacokinetics of (-)-epicatechin
      (EC) in rabbits after intravenous, intraperitoneal, and oral administration. A
      two-compartment model was used to describe the pharmacokinetics of EC after
      intravenous administration. EC showed dose-independent pharmacokinetics after
      intravenous administration. In addition, the area under the concentration-time
      curve was proportional to the dose over the range 5-25 mg/kg. After
      intraperitoneal administration of 25 mg/kg, a high percentage of EC escaped from
      first-pass hepatic elimination. After oral administration of 50 mg/kg, there was
      a great variation in the pharmacokinetics, and the mean oral bioavailability of
      EC was 4%. There was no significant difference in the elimination rate constants
      in all treatments (p>0.05). In conclusion, after intravenous, intraperitoneal,
      and oral administration of EC, the EC exhibits dose-independent pharmacokinetics
      in rabbits. The first-pass effect did not participate in the low oral
      bioavailability. Base on the results of the present study, the other factors may
      contribute the low oral bioavailability.

PMID- 19183889
TI  - Dihydroartemisinin-cyclodextrin complexation: solubility and stability.
AB  - Dihydroartemisinin (DHA) is a major metabolite of artemisinin and its
      derivatives, including arteether, artemether, and artesunate. To improve the
      solubility and stability of poorly soluble DHA, we prepared inclusion complexes
      with hydroxypropyl-beta-cyclodextrin (HPbetaCD) and recrystalized DHA to study
      its thermal stability. The complexes were characterized by differential scanning
      calorimetery (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray
      diffraction patterns (XRD), thermal stability, phase, and equilibrium solubility
      studies. Pure DHA was crystalline and remained crystalline after
      recrystallization, but its unit cell dimensions changed as exhibited by XRD. DHA
      HPbetaCD complexes showed a phase transitions towards amorphous in DSC
      thermograms, FTIR spectra, and XRD patterns. The phase solubility profiles of
      complexes prepared in water, acetate buffer, and phosphate buffers were
      classified as A(L)-type, indicating the formation of a 1:1 stoichiometric
      inclusion complex. The equilibrium solubility of DHA was enhanced as a function
      of HPbetaCD concentration. DHA-HPbetaCD complexes showed an 89-fold increase in
      solubility compared to DHA. Solubilities of complexes containing 275.1 mM
      HPbetaCD in water, acetate buffer (pH 3.0), and phosphate buffer (pH 3.0 and 7.4)
      were 10.04, 7.96, 6.30, and 11.61 mg/ml, respectively. Hydrogen bonding was found
      between DHA and HPbetaCD, and it was stronger in complexes prepared in water than
      in buffers. However, the AH values were higher in buffer than water. DHA-HPbetaCD
      complexes prepared using commercial (untreated) or recrystallized DHA (no
      detectable impurity) showed a 40% increase in thermal stability (50 degrees C)
      and a 29-fold decrease in hydrolysis rates compared with DHA. The rank order of
      stability constants (K(s)) was: water, acetate buffer (pH 3.0), phosphate buffer
      (pH 3.0), and phosphate buffer (pH 7.4). Thus, HPbetaCD complexation with
      recrystalized DHA increases DHA solubility and stability.

PMID- 19183890
TI  - From Neanderthal to nanobiotech: from plant potions to pharming with plant
      factories.
AB  - Plants were the main source for human drugs until the beginning of the nineteenth
      century when plant-derived pharmaceuticals were partly supplanted by drugs
      produced by the industrial methods of chemical synthesis. During the last decades
      of the twentieth century, genetic engineering has offered an alternative to
      chemical synthesis, using bacteria, yeasts and animal cells as factories for the
      production of therapeutic proteins. After a temporary decrease in interest,
      plants are rapidly moving back into human pharmacopoeia, with the recent
      development of plant-based recombinant protein production systems offering a safe
      and extremely cost-effective alternative to microbial and mammalian cell
      cultures. In this short review, we will illustrate that current improvements in
      plant expression systems are making them suitable as alternative factories for
      the production of either simple or highly complex therapeutic proteins.

PMID- 19183891
TI  - Cowpea mosaic virus-based systems for the expression of antigens and antibodies
      in plants.
AB  - This chapter describes the use of Cowpea mosaic virus-based vectors for the
      production of foreign proteins such as antigens and antibodies in plants. The
      systems include vectors based on both full-length and deleted versions of RNA-2.
      In both cases, the modified RNA-2 is replicated by coinoculation with RNA-1. The
      constructs based on full-length RNA-2 retain the ability to spread systemically
      throughout an inoculated plant and the infection can be passaged. The vector
      based on a deleted version of RNA-2 can stably incorporate larger inserts but
      lacks the ability to move systemically. However, it has the added advantage of
      biocontainment. In both cases, vector constructs modified to contain a foreign
      gene of interest can be delivered by agroinfiltration to obtain transient
      expression of the foreign protein. If required, the same constructs can also be
      used for stable nuclear transformation. Both types of vector have proved
      effective for the production in plants of a diverse range of proteins including
      antigens and antibodies.

PMID- 19183892
TI  - Transient expression of antibodies in plants using syringe agroinfiltration.
AB  - The improvements in agroinfiltration methods for plant-based transient expression
      now allow the production of significant amounts of recombinant proteins in a
      matter of days. While vacuum-based agroinfiltration has been brought to large
      scale to meet the cost, speed and surge capacity requirements for vaccine and
      therapeutic production, the more accessible and affordable syringe
      agroinfiltration procedure still represents a fast and high-yielding approach to
      recombinant protein production at lab scale. The procedure exemplified here has
      proven its reproducibility and high-yield capacity for the production of proteins
      with varying levels of complexity, including monoclonal antibodies.

PMID- 19183893
TI  - Rapid system for evaluating bioproduction capacity of complex pharmaceutical
      proteins in plants.
AB  - Transgene product yield remains a key limitation in commercializing plant-derived
      pharmaceutical proteins. Although significant progress has been made in
      understanding the roles of promoters, enhancers, integration sites, codon usage,
      cryptic RNA sites, silencing, and product compartmentalization on product yield
      and quality, researchers still cannot reliably predict which proteins will be
      produced at high levels or what manipulations will guarantee enhanced
      productivity. We have optimized a simple transient expression system in Nicotiana
      benthamiana enabling rapid assessment of transgene potential for plant-based
      bioproduction. Briefly, intact Nicotiana benthamiana plants are vacuum
      infiltrated with Agrobacterium tumefaciens cultures carrying the transgene of
      interest. After 48-96 h of further incubation, leaves are harvested for protein
      characterization. Using the immunomodulator interleukin-12 as a model
      pharmaceutical protein, we obtained bioactive recombinant protein at levels
      exceeding 5% of total soluble leaf protein. Appropriately assembled multimeric
      proteins have also been obtained following coinfiltration with Agrobacterium
      tumefaciens strains individually encoding each subunit. This system provides a
      rapid source of transgene product for assessing posttranslational modifications,
      purification strategies, and bioactivity as well as an effective system for
      optimizing construct elements. For vaccines, product purified from two to eight
      plants may support mouse vaccination trials providing efficacy and immune
      assessment data early in the development process.

PMID- 19183894
TI  - Production and localization of recombinant pharmaceuticals in transgenic seeds.
AB  - Among the many plant-based production systems that have been developed for
      pharmaceutical proteins, seeds have the useful advantage of accumulating proteins
      in a relatively small volume, and recombinant proteins are very stable in dry
      seeds allowing long-term storage and facilitating distribution before
      processing.To take full advantage of the natural ability of endosperm cells to
      store large amounts of protein in a protected subcellular environment, it is
      useful to target recombinant proteins to appropriate storage organelles. In this
      chapter, we describe the distinct types of protein storage organelles in the
      cereal endosperm and a protocol for the detection of recombinant proteins in
      these organelles by immunofluorescence and immunogold labelling.The use of food
      and feed crops for the production of pharmaceutical proteins such as edible
      vaccines implies the need for strict separation of the transgenic seeds from the
      food and feed chain. For improved traceability visual markers may be co-expressed
      with the gene of interest in engineered seeds. DsRed is one example for a
      fluorescent protein that can be detected with high sensitivity using low tech
      equipment. We therefore describe the generation of transgenic maize plants
      expressing DsRed in a constitutive manner, and we point out the advantages of
      using this marker during the process of transformation and selection of plant
      tissue and later during breeding of transgenic lines into elite germplasm.

PMID- 19183895
TI  - Production of antibody fragments in Arabidopsis seeds.
AB  - Plants offer a number of attractive benefits over conventional mammalian or
      bacterial cell culture systems for the production of valuable pharmaceutical and
      industrial proteins. Currently, antibodies and their derived fragments represent
      the largest and most important group of biotechnological products in clinical
      trials. In particular, single-chain antibodies are an interesting class of
      biopharmaceuticals because they are able to overcome specific problems associated
      with full-length antibodies. Another valuable antibody format is the scFv-Fc:
      fusion of the Fc domain to a single-chain variable fragment restores antibody
      effector functions, allows purification, and mimics, despite being a 'single
      gene' product, the bivalent properties of a full-length IgG. Although many
      different plant-based production platforms have been evaluated for antibody
      production, seeds are especially attractive because, as natural storage organs,
      they provide an optimal biochemical environment for the accumulation and long
      term storage of large amounts of functional proteins. This chapter describes how
      to achieve high-level seed-specific expression of antibody fragments, how to
      select the best transgenic lines, and how to evaluate the accumulation level in
      the seed stocks from the selected lines.

PMID- 19183896
TI  - Production of plantibodies in Nicotiana plants.
AB  - Because of the wide use and high demand in medicine, monoclonal antibodies are
      among the main recombinant pharmaceuticals at present, although present
      limitations of the productive platforms for monoclonal antibodies are driving the
      improvement of the large-scale technologies and the development of alternative
      expression systems. This has drawn the attention on plants as expression system
      for monoclonal antibodies and related derivatives, owning the capacity of plants
      to properly express and process eukaryotic proteins with biological activity
      resembling that of the natural proteins. In this chapter, the procedures from the
      isolation of the monoclonal antibody genes to the biochemical and biological
      characterization of the plant-expressed monoclonal antibody are described.

PMID- 19183897
TI  - Physcomitrella patens: a non-vascular plant for recombinant protein production.
AB  - The moss Physcomitrella patens is a long-standing model for studying plant
      development, growth and cell differentiation in particular. Interest in this non
      vascular plant arose following the discovery that homologous recombination is an
      efficient process. P. patens is, therefore, a tool of choice not only to study
      gene function but also for recombinant protein production. This system has many
      attributes that are advantageous for molecular farming: protein production in
      cell suspension, the possibility of generating targeted knockout mutants for
      glycoengineering and quantitative optimization for protein production. In terms
      of technical advances, P. patens is one of the most up-to-date plant expression
      systems and is a promising alternative to animal cell factories for the
      production of therapeutic proteins with either simple or highly complex
      structures.

PMID- 19183898
TI  - Production of recombinant proteins in suspension-cultured plant cells.
AB  - Plants have emerged in the past decade as a suitable alternative to the current
      production systems for recombinant pharmaceutical proteins and, today their
      potential for low-cost production of high quality, much safer and biologically
      active mammalian proteins is largely documented. Among various plant expression
      systems being explored, genetically modified suspension-cultured plant cells
      offer a promising system for production of biopharmaceuticals. Indeed, when
      compared to other plant-based production platforms that have been explored,
      suspension-cultured plant cells have the advantage of being totally devoid of
      problems associated with the vagaries of weather, pest, soil and gene flow in the
      environment. Because of short growth cycles, the timescale needed for the
      production of recombinant proteins in plant cell culture can be counted in days
      or weeks after transformation compared to months needed for the production in
      transgenic plants. Moreover, recovery and purification of recombinant proteins
      from plant biomass is an expensive and technically challenging business that may
      amount to 80-94% of the final product cost. One additional advantage of plant
      cell culture is that the recombinant protein fused with a signal sequence can be
      expressed and secreted into the culture medium, and therefore recovered and
      purified in the absence of large quantities of contaminating proteins.
      Consequently, the downstream processing of proteins extracted from plant cell
      culture medium is less expensive, which may/does balance the higher costs of
      fermentation. When needed for clinical use, recombinant proteins are easily
      produced in suspension-cultured plant cells under certified, controllable and
      sterile conditions that offer improved safety and provide advantages for good
      manufacturing practices and regulatory compliance. In this chapter, we present
      basic protocols for rapid generation of transgenic suspension-cultured cells of
      Nicotiana tabacum, Oriza sativa and Arabidopis thaliana. These systems are
      powerful tools for plant-made pharmaceuticals production in highly controlled
      conditions.

PMID- 19183899
TI  - Chloroplast-derived vaccine antigens and biopharmaceuticals: protocols for
      expression, purification, or oral delivery and functional evaluation.
AB  - Many vaccine antigens and biopharmaceutical proteins have been expressed at high
      levels via the chloroplast genome and their functionality has been evaluated
      using in vitro assays in cell cultures (i.e., macrophage lysis assay, inhibition
      of vesicular stomatitis virus-induced cytopathicity in baby hamster kidney cells,
      or inhibition of human HIV infection in TZM-BL cells) as well as protection after
      challenge with bacterial or viral pathogens or antitumor assays or delay the
      onset of insulitis in suitable animal models. Production of therapeutic proteins
      in chloroplasts eliminates the expensive fermentation technology. Moreover, oral
      delivery of chloroplast-derived therapeutic proteins eliminates expensive
      purification steps, cold storage, cold transportation, and delivery via sterile
      needles, thereby further decreasing their cost. In this chapter, we describe
      detailed protocols for chloroplast transformation including the construction of
      chloroplast transformation vectors, delivery of DNA into plant cells using
      particle bombardment, selection and regeneration of transformants by tissue
      culture, confirmation of transgene integration into the chloroplast genome and
      homoplasmy, evaluation of foreign gene expression, purification of foreign
      protein, or oral delivery via bioencapsulation, functional evaluation using in
      vitro and in vivo assays, and evaluation of immunity after challenge with
      pathogens in suitable animal models.

PMID- 19183900
TI  - Protein body induction: a new tool to produce and recover recombinant proteins in
      plants.
AB  - Stable accumulation of storage proteins, lipids and carbohydrates is a hallmark
      of the plant seed, and is a characteristic that is typically deficient in
      existing platforms for recombinant protein manufacture. One of the biological
      sequestration mechanisms that facilitate the folding, assembly and stabilization
      of plant seed storage proteins involve the de novo formation of unique
      intracellular organelles, the endoplasmic reticulum (ER)-derived protein bodies
      (PBs). In cereals, such as maize, PBs are formed directly in the lumen of the ER
      of endosperm cells and contain zeins, a group of polypeptides, which account for
      more than half of the total seed protein mass. The 27 kD gamma zein protein
      localizes to the periphery of the PBs surrounding aggregates of other zeins
      (including a zein and delta zein). Heterologous expression of gamma zein has been
      shown to result in the formation of PB-like structures, and the N-terminal
      proline-rich domain of gamma zein (Zera), containing eight PPPVHL repeats and a
      Pro-X sequence is by itself capable of directing ER retention and PB formation in
      non-seed tissues. We present a novel approach to produce recombinant proteins in
      plants based on the ability of gamma zein-Zera domain to store recombinant
      proteins inside PBs. Zera domain fused to several proteins, including a enhanced
      cyan fluorescent protein (ECFP), calcitonin (Ct) and epidermal growth factor
      (EGF), were cloned into vectors for transient or stable transformation of tobacco
      plants. In tobacco leaves, we observed the formation of dense, ER-localized
      structures containing high concentrations of the respective target proteins. The
      intact synthetic organelles containing Zera fusions were readily isolated from
      cellular material using density-based separation methods.

PMID- 19183901
TI  - A case study for plant-made pharmaceuticals comparing different plant expression
      and production systems.
AB  - Over the last decade, plant-based production of pharmaceuticals has made
      remarkable progress as the expression of a diverse set of proteins has been
      demonstrated in a range of plant crops. Although the commercial exploitation is
      still pending, today various plant-based expression technologies have reached
      significant milestones through clinical testing in humans. Each of the protein
      manufacturing platforms in plants has specific benefits and drawbacks. We have
      engaged in comparing some of these production systems with respect to their
      performance: protein yield and quality. Using a specific tester protein
      (aprotinin), it was shown that functional aprotinin can be manufactured in plants
      in substantial amounts, as illustrated in this chapter.

PMID- 19183902
TI  - Glycosylation of antibody therapeutics: optimisation for purpose.
AB  - Recombinant antibody therapeutics represent a significant success story in terms
      of clinical benefit delivered and revenue (profit) generated within the
      biopharmaceutical industry. Additionally, it is estimated that 30% of new drugs
      likely to be licensed during the next decade will be based on antibody products.
      High volume production with the maintenance of structural and functional fidelity
      of these large biological molecules results in high "cost of goods" that can
      limit their availability to patients, due to the strain it puts on national and
      private health budgets. The challenge in reducing cost of goods is that each
      antibody is unique, both in structure and function. Optimal clinical efficacy
      will require engineering of antibody genes to deliver products with enhanced
      activities produced by cell lines engineered to deliver antibody homogeneous for
      pre-selected post-translational modifications, that is, protein structures and
      glycoforms. A "universal" production vehicle cannot meet these demands and
      several production mammalian cells are now available, alternatives to mammalian
      cell lines are also reaching maturity. Advances in downstream processing also
      need to be realised whilst chemical changes during processing and storage must be
      minimised.

PMID- 19183903
TI  - N-glycosylation of plant recombinant pharmaceuticals.
AB  - N-glycosylation is a maturation event necessary for the correct function,
      efficiency, and stability of a high number of biopharmaceuticals. This chapter
      presented here proposes various methods to determine whether, how, and where a
      plant pharmaceutical is N-glycosylated. These methods rely on blot detection with
      glycan-specific probes, specific deglycosylation of glycoproteins followed by
      mass spectrometry, N-glycan profile analysis, and glycopeptide identification by
      LC-MS.

PMID- 19183904
TI  - Companion protease inhibitors to protect recombinant proteins in transgenic plant
      extracts.
AB  - We describe a general approach for the use of recombinant protease inhibitors as
      stabilizing agents for clinically useful proteins extracted from transgenic plant
      tissues. A procedure is first described to assess the overall (in)stability of
      heterologous proteins in transgenic plant crude protein extracts. Step-by-step
      protocols are then presented for the choice and use of companion protease
      inhibitors inhibiting the host plant proteases during extraction. This strategy,
      that reproduces the protein-stabilizing effect of low-molecular-weight protease
      inhibitors often added to protein extraction media, does not require the
      exogenous addition of such expensive and often toxic compounds. It also presents
      the advantage of being intrinsically scalable to the amount of biomass processed.

PMID- 19183905
TI  - Strategies for improving vaccine antigens expression in transgenic plants: fusion
      to carrier sequences.
AB  - Transgenic plants are gaining increasing attention from the industry as a natural
      bioreactor for the production of industrial and chemical products. Optimization
      of transgene expression in plant cells holds the key to maximizing the potential
      of plants for producing proteins of commercial interest. This chapter is devoted
      to the description of the methods utilized for the generation of transgenic
      plants expressing a canine parvovirus vaccine peptide or virus-like particles
      from a rabbit calicivirus.

PMID- 19183906
TI  - Immunomodulation of plant function by in vitro selected single-chain Fv
      intrabodies.
AB  - In this chapter, we discuss and compare the different concepts and examples as
      well as present the basic protocols for applying intrabody-based approaches in
      plants for the investigation of cell functions and plant cell-pathogen
      interactions. The immunomodulation strategy, a molecular technique that allows to
      interfere with cellular metabolism, signal transduction pathways, or pathogen
      infectivity, is based on the ectopic expression of genes encoding specific
      recombinant antibodies. This needs basic prerequisites to be successfully applied
      as resources and techniques to isolate specific recombinant antibodies with
      sufficient binding parameters to bind and to block even low-concentrated targets
      or to compete successfully with substrates and ligands. Also techniques and
      constructs to efficiently transform plants and to target recombinant antibodies
      to selected compartments are important requirements. Basic protocols for all
      these techniques are provided.

PMID- 19183907
TI  - On-chip detection of low-molecular-weight recombinant proteins in plant crude
      extracts by SELDI-TOF MS.
AB  - This chapter presents a general procedure for the on-chip detection and
      quantitation of low-molecular-weight recombinant proteins in transgenic plant
      crude extracts by surface-enhanced laser desorption ionization time-of-flight
      mass spectrometry (SELDI-TOF MS). A protocol is first described to detect the
      protein of interest in crude protein extracts of transgenic plant lines, by
      differential protein mapping against similar extracts from a control,
      nontransgenic line. A complementary protocol is then presented to generate a
      standard curve with the SELDI system, allowing the protein to be quantified in
      different transgenic lines. Overall, this procedure may be carried out within a
      few hours, without the need for prior purification or enrichment of the
      recombinant protein.

PMID- 19183908
TI  - Assessing the risk of undesirable immunogenicity/allergenicity of plant-derived
      therapeutic proteins.
AB  - Therapeutic proteins have an intrinsic potential to induce undesirable immune and
      allergic responses. The nature of the expression system and the control of the
      manufacturing process represent extrinsic factors that could modify this
      potential. Accordingly, regulatory agencies require sponsors to assess the risk
      of clinical immune and allergic responses that could be associated with the
      production of therapeutic proteins in transgenic plants. Since factors related to
      the clinical use of the product--including the immune status and genetic
      background of subjects--are also relevant, the risk assessment needs to balance
      the probability of a response induced by a plant-specific factor relative to the
      likely consequences for the specific product and therapeutic indication.

PMID- 19183909
TI  - Biosafety, risk assessment and regulation of plant-made pharmaceuticals.
AB  - The technology for plant-made pharmaceuticals (PMPs) has progressed significantly
      over the last few years, with the first commercial products for human use
      expected to reach the market by 2009 (see Note 1). As part of the 'next
      generation' of genetically modified (GM) crops, PMPs will be subject to
      additional biosafety considerations and are set to challenge the complex and
      overlapping regulations that currently govern GM plants, plant biologics (see
      Note 2) and 'conventional' pharmaceutical production. The areas of responsibility
      are being mapped out between the different regulatory agencies (Sparrow, P.A.C.,
      Irwin, J., Dale, P., Twyman, R.M., and Ma, J.K.C. (2007) Pharma-Planta: Road
      testing the developing regulatory guidelines for plant-made pharmaceuticals.
      Transgenic Res., 2007), with specific guidelines currently being drawn up for the
      regulation of PMPs. In this chapter, we provide an overview of the biosafety (see
      Note 3), risk assessment (see Note 4) and regulation of this emerging technology.
      While reference will be made to EU regulations, the underlying principles of
      biosafety and risk assessment are generic to most countries.

PMID- 19183910
TI  - [Life phase specific health of children and adolescents in Germany. Results of
      the National Child and Youth Health Survey].

PMID- 19183911
TI  - [Historical aspects concerning the symptom of itch in the German-speaking region
      (1850-1939)].
AB  - Since the establishment of dermatology as an independent discipline of medicine
      in the middle of the 19th century, pruritus or itch has been a subject of
      research. The goals were to discover the etiology of pruritus, to develop useful
      therapies and to achieve a classification within the system of skin diseases.
      Looking at historical aspects of pruritus demonstrates just how difficult it has
      been to approach this problem. The difficulties even influence present day
      pruritus research. For example, there is no definite international standard of
      pruritus. Etiology-oriented classifications have dominated, but have recently
      been supplemented by a clinical classification.

PMID- 19183913
TI  - [Squamous intraepithelial neoplasia (WHO 2005). Precancerous lesions of the head
      and neck region].
AB  - The recent WHO classification 2005 applies the concept of intraepithelial
      neoplasia to the head and neck region. Precursor lesions of the head and neck
      mucosa are classified as squamous intraepithelial neoplasia (SIN) and are graded
      as mild, moderate and severe (SIN 1-3). SIN 3 is equivalent to former carcinoma
      in situ. Each precursor lesion is associated with an ascertained risk of
      progression to carcinoma, which is important for further diagnostic or therapy.

PMID- 19183912
TI  - [Therapeutic strategies for psoriasis and psoriatic arthritis].
AB  - Psoriasis is a chronic, immune-mediated inflammatory disorder with a genetic
      background, whose treatment is currently undergoing a paradigm shift. For many
      patients clinical signs and symptoms of psoriatic skin and joint disease are most
      important. From the public health perspective, however, recent findings that
      suggest a high degree of co-morbidity is becoming increasingly relevant. Because
      it is also highly significant from the patients' perspective, the improvement of
      health-related quality of life should be considered as the third treatment goal.
      Modern therapeutic concepts interact with specific pathogenetically relevant
      molecular targets. The development of such"targeted therapies" reflects our
      increasing understanding of the pathogenetic principles of psoriasis. Provided
      that the whole spectrum of approved remedies is employed as indicated, psoriasis
      has become a condition that is amenable to early intervention and can be treated
      effectively in the long run.

PMID- 19183914
TI  - [Voice diagnostics in professional sopranos: application of the protocol of the
      European Laryngological Society (ELS)].
AB  - The European Laryngological Society (ELS) has published a protocol for the
      evaluation of vocal function. Using this protocol, we evaluated 17 female
      sopranos, of whom 11 had laryngostroboscopic findings of organic alterations and
      six did not. Singers with increased subjective impressions of hoarseness, or of
      whom the examiner had increased perceptions of hoarseness, showed significant
      differences regarding impairment of the maximum phonation time, the frequency
      range, and the dysphonia severity index. No such differences were found regarding
      the presence of alterations of the vocal folds. These data suggest that organic
      alterations in professional singers are not necessarily associated with impaired
      vocal performance or vocal function or with measured values of the ELS protocol.
      For professional singers, therapy should be indicated not just on the basis of
      stroboscopy but on a broader basis using multifactorial voice analysis such as
      the ELS protocol.

PMID- 19183915
TI  - [Gigantic nasal tumor].
AB  - A space-occupying lesion, which had been growing on the external surface of the
      nose of a 57-year-old man for 5 years was considered to most likely be an
      angiofibroma after surgical removal and histological examination, but the final
      clinical diagnosis was clearly a rhinophyma. This discrepancy is relevant for
      surgical treatment, because the vessel-rich tumor tended to substantial
      intraoperative bleeding.

PMID- 19183916
TI  - [A new gene locus for an autosomal-dominant non-syndromic hearing impairment
      (DFNA 33) is situated on chromosome 13q34-qter].
AB  - By investigation of a German family pedigree with non-syndromic hearing
      impairment of early onset and autosomal-dominant mode of inheritance, linkage to
      known DFNA loci was excluded, and the existence of a new locus (DFNA33) was
      revealed. In a subsequent genomic scan the phenotype was mapped to a 6 cM
      interval on chromosome 13q34-qter. A maximum two-point lod score of 2.96 was
      obtained for the marker D13S285 with a maximum lod score in the multipoint
      analysis of 3.28 at 124.56 cM.

PMID- 19183917
TI  - [Laryngeal granuloma. Aetiology, clinical signs, diagnostic procedures, and
      treatment].
AB  - Vocal cord granulomas are benign inflammatory lesions of the vocal cords. They
      are usually located over the vocal process of the arytenoid cartilage. A
      corresponding ulcer on the contralateral side is a common finding. Clinical signs
      include foreign body sensation, a need to repeatedly clear one's throat,
      hoarseness, and reduced voice resilience. Voice abuse and gastro-oesophageal
      reflux are commonly cited important aetiological factors. Differentiation from
      malignant lesions is usually possible by history and clinical examination; biopsy
      is only rarely necessary. The primary treatment is speech therapy or voice
      counselling, if necessary, supported by antacids. Surgical excision is not
      helpful because contact granulomas tend to recur. We present two typical cases of
      vocal cord granulomas and discuss their management.

PMID- 19183918
TI  - [Reproducibility and reliability of phonovibrograms. Quantification of healthy
      vocal fold vibrations].
AB  - BACKGROUND: Phonovibrography is capable of visualizing vocal fold vibrations in a
      static two-dimensional image, the so-called phonovibrogram (PVG). It allows
      quantification of the entire vocal fold vibration patterns. In this study we
      investigated the accuracy and reproducibility of PVG measures by analyzing high
      speed laryngoscopy videos of healthy vocal fold vibrations. METHODS: High-speed
      laryngoscopy videos of 12 female speech therapists and 12 vocalists from the
      Regensburg Cathedral choir were analyzed. For evaluation purposes, PVG analysis
      was performed for two different sections of each video. RESULTS: The mean
      difference between the high-speed sections was 1.6 degrees +/-0.5 degrees for the
      female and 2.3 degrees +/-0.6 degrees for the male subjects. Within the sections,
      the mean variance of the PVG parameters was 3.5 degrees +/-0.7 degrees
      (therapists) and 3.7 degrees +/-1.0 degrees (vocalists). Likewise, a high
      left/right accordance of the PVG parameters, 5.3 degrees +/-0.5 degrees for
      therapists and 5.9 degrees +/-1.9 degrees for vocalists, was obtained.
      CONCLUSION: Vibrational patterns of normal vocal fold vibrations were very
      precisely quantified by the introduced PVG parameters. The high accuracy and
      reproducibility of PVG analysis provides a basis for prospective clinical trials
      dealing with precise characterization of pathological vibration patterns.

PMID- 19183919
TI  - [Optimal therapeutic strategy in type 2 diabetes mellitus].

PMID- 19183920
TI  - [Antidepressive pharmacotherapy. In slight and severe disease, young and old].
AB  - During the past decade a variety of promising new compounds launched onto the
      market not only enhancing serotonergic and noradrenergic neurotransmission, but
      also influencing the dopamine and the melatonergic receptor system. In spite of
      misleading discussions both in the specialized and in the lay press the clinical
      effectiveness of antidepressants still is indisputable. The main advantages of
      the newer drugs are the broadening of the spectrum treatments and a far better
      tolerability profile in comparison to older compounds. Predominantly depression
      of medium to high severity should be treated pharmacologically. Especially severe
      depression seems to respond better to dually acting antidepressants. In children
      effectiveness of Omega3-fatty acids has been shown, in adolescents SSRI treatment
      was efficacious. Older patients respond to all antidepressant mechanisms, but
      more selective substances should be preferred due to a better tolerability. The
      study of new treatment options is of major importance to provide better
      strategies for the clinical management of depression in the future, and is thus
      also of great socio-economic importance.

PMID- 19183921
TI  - [52 year-old patient with severe heart failure due to multiple myeloma].
AB  - Cardiac amyloidosis represents a prognostically relevant comorbidity in multiple
      myeloma. We report the case of a patient in whom severe heart failure symptoms as
      a consequence of cardiac AL-amyloidosis resolved after tandem high-dose melphalan
      therapy followed by autologous blood-stem cell transplantation. Partial
      regression of cardiac amyloid deposits and improvement of cardiac function were
      objectified.

PMID- 19183923
TI  - ?

PMID- 19183922
TI  - [Important steps toward a comprehensive network for care of severe injuries].

PMID- 19183924
TI  - [A novel knee endoprosthesis with a physiological joint shape. Part 1:
      Biomechanical basics and tribological studies].
AB  - The natural tibiofemoral joint (TFJ) functions according to a roll-glide
      mechanism. In the stance phase (0-20 degrees flexion), the femur rolls backwards
      over the tibia plateau, while further flexion causes increased gliding. This
      kinematics is based on the principle of a quadruple joint. The four morphological
      axes of rotation are the midpoints of the curvatures of the medial and lateral
      femoral condyles and the medial and lateral tibia plateau. In addition, the
      medial and lateral compartments are shifted a few millimetres in a sagittal
      direction, the medial tibia plateau being concave and the lateral plateau convex.
      In most knee arthroplasties, these factors are not taken into account; instead
      they are equipped with symmetrical medial and lateral joint surfaces. Thereby,
      the midpoints of the curvatures of the sagittal contours of the lateral and
      medial joint surfaces, on the femoral as well as on the tibial sides, create a
      common axis of rotation which does not allow a physiological roll-glide
      mechanism. The goal of this study was therefore to report on the biomechanical
      basis of the natural knee and to describe the development of a novel knee
      endoprosthesis based on a mathematical model. The design of the structurally new
      knee joint endoprosthesis has, on the lateral side, a convex shape of the tibial
      joint surface in a sagittal cross section. Furthermore, from a mathematical point
      of view, this knee endoprosthesis possesses essential kinematic and static
      properties similar to those of a physiological TFJ. Within the framework of the
      authorization tests, the endoprosthesis was examined according to ISO/WC 14243 in
      a knee simulator. The abrasion rates were, thereby, lower than or at least as
      good as those for conventional endoprostheses. The presented data demonstrate a
      novel concept in knee arthroplasty, which still has to be clinically confirmed by
      long term results.

PMID- 19183925
TI  - [Physicians in traumatology. Critically endangered? Results of an inquiry].
AB  - INTRODUCTION: The aim of this investigation was to describe the current situation
      and atmosphere among residents and consultants in traumatology, using the results
      of a questionnaire. Wishes and needs concerning training programs in traumatology
      were addressed. METHODS: A questionnaire consisting of 25 items was distributed
      among members of the German Society of Traumatology (DGU) to document basic data
      concerning the state of residency and physicians' current workload. The
      participants were also asked about their personal interests and aims within
      traumatology. Finally, questions concerning educational programs, compensation,
      and work-life balance were addressed. The results were analysed descriptively.
      RESULTS: The final analysis included 549 questionnaires. The mean age of the
      participants was 36 years (SD +/-7.5). Sixty percent (329) were residents, and
      16% (88) served as consultants. The mean workload per week was 61 h (SD +/-10.8
      h), and participants were on call seven times (SD +/-5.6) a month. The work-life
      balance was rated a mean of only 5 ("mediocre"). The majority of participants
      rejected working longer in order to reduce the duration of their educational
      program. On the other hand, most of the participants would also reject a
      reduction in working time accompanied by a reduced salary. Nevertheless, 78%
      (428) of the participants would, in retrospect, choose the same profession, and
      85% (466) would even choose the same specialty. DISCUSSION: The study reports on
      the atmosphere among residents and consultants in traumatology. Despite European
      regulations, the individual workload is exceptionally high. It is a clear task of
      hospital administrators to increase the attractiveness of hospital jobs in order
      to ensure qualified personnel in the future.

PMID- 19183926
TI  - [Rituximab in treatment for neuroimmunological diseases].
AB  - Rituximab, a human-mouse chimeric CD20 monoclonal antibody that depletes CD20
      positive B cells, has already demonstrated efficacy in hematologic and
      rheumatologic diseases. Treatment with rituximab results in depletion of CD20
      positive cells via multiple mechanisms, including complement-mediated or antibody
      dependent cytotoxicity and apoptosis. Recent histopathologic and immunologic
      studies reveal an influence of B cells on the development and perpetuation of
      many chronic inflammatory diseases of the nervous system. Promising results with
      rituximab were already reported in the therapy of myasthenia gravis,
      immunoneuropathies, neuromyelitis optica, and multiple sclerosis, in which first
      controlled studies have been recently published. In this review we summarize
      available data from these reports and also discuss possible underlying molecular
      mechanisms.

PMID- 19183927
TI  - [Arterial embolization of hepatic metastases from neuroendocrine tumors].
AB  - Neuroendocrine tumors are slowly growing neoplasms and 75% of patients already
      present with hepatic metastases at the time of diagnosis. Size and growth of
      liver metastases is of prognostic value. Due to arterial vascularization of
      metastases, transarterial embolization (TAE) is a suitable procedure, which can
      also be combined with chemotherapeutic agents. Indications for embolization or
      chemoembolization (TACE) are growth of liver metastases or inadequate symptom
      control. The majority of patients show clinical improvement and partial remission
      can be achieved in 50% of cases with 5-year survival rates of 50-60%. Response
      rates, survival or complications are not dependent on the embolization technique
      (TAE or TACE). Embolization is usually performed in several sessions depending on
      individual tumor stage and disease progression. Embolization is a cost-effective
      procedure and is included in the treatment algorithm of international guidelines.
      Therefore, evaluation of new embolization therapies must be evaluated in
      randomized controlled studies.

PMID- 19183928
TI  - [Thulium:YAG vaporesection of the prostate. First results].
AB  - OBJECTIVES: Laser treatment of benign prostatic hyperplasia has been introduced.
      The thulium:YAG (Tm:YAG) laser combines the advantages of established laser
      systems. This study reports the preliminary results of vaporesection of the
      prostate, using this 2-microm continuous wave (cw) laser. MATERIAL AND METHODS: A
      total of 54 consecutive patients were treated with the Tm:YAG laser. The outcomes
      measured were resection time, catheter time, improvement in urinary flow rate
      (Q(max)), and post-voiding residual urine (PVR). International Prostate Symptom
      Score (IPSS) and Quality of Life Index (QoL) were recorded. RESULTS: The mean age
      was 61 years. Mean prostate volume was 30.3 cc. Average resection time was 52
      min. Catheter time was 1.7 days. Qmax significantly improved from 4.2 to 20.9 ml
      on average. PVR decreased from 86 to 16 ml. IPSS and QoL score improved from 19.8
      to 6.5 and 4 to 1, respectively. No patient required re-hospitalization.
      Transfusions were not necessary. CONCLUSIONS: These preliminary results indicate
      that Tm:YAG vaporesection of the prostate is safe and efficient. The 18-month
      follow-up data showed major improvement in voiding symptoms and QoL. Longer
      follow-up is needed to prove durability of these promising results.

PMID- 19183929
TI  - [Results of the randomised phase III study of the German Testicular Cancer Study
      Group. Retroperitoneal lymphadenectomy versus one cycle BEP as adjuvant therapy
      for non-seminomatous testicular tumours in clinical stage I].
AB  - OBJECTIVE: As 30% of non-seminomas in clinical stage I will progress during
      active surveillance, alternative adjuvant strategies of 2 cycles of bleomycin,
      etoposid, cisplatin (BEP) or nerve sparing retroperitoneal lymphadenectomy
      (RPLND) can be offered. The risk of relapse is reduced to 2% and 10%,
      respectively. Without prognostic markers and with lowered toxicity it is
      postulated that only one cycle of BEP could significantly reduce the recurrence
      rate in comparison to RPLND. MATERIALS AND METHODS: Between 1996 and 2005, 382
      patients were randomly assigned to receive either RPLND (n=191) or 1 cycle of BEP
      (n=191). In accordance with the protocol, 174 patients were treated with 1 cycle
      of BEP and 173 underwent RPLND. The primary study end-point was a reduction of
      recurrence from 10% after RPLND to a maximum of 3% after 1 cycle of BEP. RESULTS:
      After a mean follow-up of 4.7 years, there were 2 and 13 recurrences in the
      according-to-protocol population with chemotherapy and surgery, respectively. The
      difference between chemotherapy (1.15%) and surgery (7.5%) was statistically
      significant (p=0.0033). The tumor-specific survival was 100%. CONCLUSION: This
      largest randomized trial investigating treatment strategies in clinical stage I
      non-seminomas (AUO AH 01/94) showed the superiority of one cycle BEP over RPLND.
      The data obtained represent the basis for a reduced chemotherapy.

PMID- 19183930
TI  - [Is medical therapy useful in the management of stress urinary incontinence?].
AB  - In Germany, only duloxetine is registered for treating stress urinary
      incontinence in adult women; duloxetine treatment for stress urinary incontinence
      in children or men is poorly investigated and still off-label. Trials in women
      based on the evidence level 1B and meta-analyses have demonstrated that
      duloxetine significantly reduced the frequency of incontinence episodes and
      increased incontinence-related quality of life. However, duloxetine must be used
      on a regular base to maintain these positive effects. Therefore, duloxetine seems
      to be especially indicated in women who refuse or cannot be subjected to physical
      or surgical treatment and are willing to accept the long-term use and possible
      side effects of the drug. Furthermore, duloxetine could be useful in women to
      support pelvic floor physiotherapy or in female patients awaiting incontinence
      surgery.

PMID- 19183931
TI  - [Drug-drug interactions in urology].
AB  - Many patients concomitantly receive multiple urological and nonurological
      medications. This practice can lead to drug-drug interactions (DDIs). These
      interactions can be pharmacodynamic (acting on the same body function) or
      pharmacokinetic (affecting each other's concentrations) and are a frequent cause
      of adverse drug reactions. Examples of pharmacodynamic DDIs include the use of
      overactive bladder drugs together with those prescribed for psychiatric or
      neurological indications that also have anticholinergic properties, or the use of
      PDE5 inhibitors together with vasodilating drugs, particularly nitrates.
      Pharmacokinetic DDIs are mainly due to effects on drug metabolism, specifically
      that involving CYP3A4 and 2D6, or on drug transporters. Drugs can both inhibit
      and induce the activity of many of these enzymes and transporters. CYP3A4
      inducers can lower levels of cyclosporine or tacrolimus so much that transplant
      rejection occurs, and CYP3A4 inhibitors can increase their levels, leading to
      nephrotoxicity. Levels of the anticholinergic darifenacin can be increased so
      much by potent CYP3A4 inhibitors that this combination is contraindicated. These
      examples show that knowledge of DDI can help patients avoid undesirable side
      effects of drugs.

PMID- 19183932
TI  - PPARGC1A sequence variation and cardiovascular risk-factor levels: a study of the
      main genetic effects and gene x environment interactions in children from the
      European Youth Heart Study.
AB  - AIMS/HYPOTHESIS: The PPARGC1A gene coactivates multiple nuclear transcription
      factors involved in cellular energy metabolism and vascular stasis. In the
      present study, we genotyped 35 tagging polymorphisms to capture all common
      PPARGC1A nucleotide sequence variations and tested for association with metabolic
      and cardiovascular traits in 2,101 Danish and Estonian boys and girls from the
      European Youth Heart Study, a multicentre school-based cross-sectional cohort
      study. METHODS: Fasting plasma glucose concentrations, anthropometric variables
      and blood pressure were measured. Habitual physical activity and aerobic fitness
      were objectively assessed using uniaxial accelerometry and a maximal aerobic
      exercise stress test on a bicycle ergometer, respectively. RESULTS: In adjusted
      models, nominally significant associations were observed for BMI (rs10018239, p =
      0.039), waist circumference (rs7656250, p = 0.012; rs8192678 [Gly482Ser], p =
      0.015; rs3755863, p = 0.02; rs10018239, beta = -0.01 cm per minor allele copy, p
      = 0.043), systolic blood pressure (rs2970869, p = 0.018) and fasting glucose
      concentrations (rs11724368, p = 0.045). Stronger associations were observed for
      aerobic fitness (rs7656250, p = 0.005; rs13117172, p = 0.008) and fasting glucose
      concentrations (rs7657071, p = 0.002). None remained significant after correcting
      for the number of statistical comparisons. We proceeded by testing for gene x
      physical activity interactions for the polymorphisms that showed nominal evidence
      of association in the main effect models. None of these tests was statistically
      significant. CONCLUSIONS/INTERPRETATION: Variants at PPARGC1A may influence
      several metabolic traits in this European paediatric cohort. However, variation
      at PPARGC1A is unlikely to have a major impact on cardiovascular or metabolic
      health in these children.

PMID- 19183933
TI  - The inflammatory receptor CD40 is expressed on human adipocytes: contribution to
      crosstalk between lymphocytes and adipocytes.
AB  - AIMS/HYPOTHESIS: Obesity is associated with adipose tissue inflammation. The CD40
      molecule, TNF receptor superfamily member 5 (CD40)/CD40 ligand (CD40L) pathway
      plays a role in the onset and maintenance of the inflammatory reaction, but has
      not been studied in human adipose tissue. Our aim was to examine CD40 expression
      by human adipocytes and its participation in adipose tissue inflammation.
      METHODS: CD40 expression was investigated in human whole adipose tissue and
      during adipocyte differentiation by real-time PCR, Western blot and
      immunohistochemistry. The CD40/CD40L pathway was studied using recombinant CD40L
      (rCD40L) in adipocyte culture and neutralising antibodies in lymphocyte/adipocyte
      co-culture. RESULTS: CD40 mRNA levels in subcutaneous adipose tissue were higher
      in the adipocyte than in the stromal-vascular fraction. CD40 expression was
      upregulated during adipocyte differentiation. Addition of rCD40L to adipocytes
      induced mitogen activated protein kinase (MAPK) activation, stimulated
      inflammatory adipocytokine production, and decreased insulin-induced glucose
      transport in parallel with a downregulation of IRS1 and GLUT4 (also known as
      SCL2A4). rCD40L decreased the expression of lipogenic genes and increased
      lipolysis. CD40 mRNA levels were significantly higher in subcutaneous adipose
      tissue than in visceral adipose tissue of obese patients and were positively
      correlated with BMI, and with IL6 and leptin mRNA levels. Lymphocyte/adipocyte co
      culture led to an upregulation of proinflammatory adipocytokines and a
      downregulation of leptin and adiponectin. Physical separation of the two cell
      types attenuated these effects, suggesting the involvement of a cell-cell
      contact. Blocking the CD40/CD40L interaction with neutralising antibodies reduced
      IL-6 secretion from adipocytes. CONCLUSIONS/INTERPRETATION: Adipocyte CD40 may
      contribute to obesity-related inflammation and insulin resistance. T lymphocytes
      regulate adipocytokine production through both the release of soluble factor(s)
      and heterotypic contact with adipocytes involving CD40.

PMID- 19183934
TI  - TCF7L2 variants are associated with increased proinsulin/insulin ratios but not
      obesity traits in the Framingham Heart Study.
AB  - AIMS/HYPOTHESIS: Common variants in the TCF7L2 gene are associated with type 2
      diabetes via impaired insulin secretion. One hypothesis is that variation in
      TCF7L2 impairs insulin processing in the beta cell. In contrast, the association
      of related TCF7L2 polymorphisms with obesity is controversial in that it has only
      been shown in cohorts susceptible to ascertainment bias. We reproduced the
      association of diabetes-associated variants with proinsulin/insulin ratios, and
      also examined the association of a TCF7L2 haplotype with obesity in the
      Framingham Heart Study (FHS). METHODS: We genotyped the TCF7L2 single nucleotide
      polymorphisms rs7903146 and rs12255372 (previously associated with type 2
      diabetes) and rs10885406 and rs7924080 (which tag haplotype A [HapA], a haplotype
      reported to be associated with obesity) in 2,512 FHS participants. We used age-
      and sex-adjusted linear mixed-effects models to test for association with
      glycaemic traits, proinsulin/insulin ratios and obesity measures. RESULTS: As
      expected, the T risk allele of rs7903146 was associated with higher fasting
      plasma glucose (p = 0.01). T/T homozygotes had a 23.5% increase in the
      proinsulin/insulin ratio (p = 1 x 10(-7)) compared with C/C homozygotes. There
      was no association of HapA with BMI (p = 0.98), waist circumference (p = 0.89),
      subcutaneous adipose tissue (p = 0.32) or visceral adipose tissue (p = 0.92).
      CONCLUSIONS/INTERPRETATION: We confirmed that the risk allele of rs7903146 is
      associated with hyperglycaemia and a higher proinsulin/insulin ratio. We did not
      detect any association of the TCF7L2 HapA with adiposity measures, suggesting
      that this may have been a spurious association from ascertainment bias, possibly
      induced by the evaluation of obesity in separate groups of glycaemic cases and
      controls.

PMID- 19183935
TI  - Mitochondrial reactive oxygen species generation in obese non-diabetic and type 2
      diabetic participants.
AB  - AIMS/HYPOTHESIS: The aim of this study was to measure mitochondrial reactive
      oxygen species (ROS) production directly from skeletal muscle biopsies obtained
      from obese insulin-resistant non-diabetic and type 2 diabetic participants.
      METHODS: Ten lean healthy, ten obese non-diabetic and ten type 2 diabetic
      participants received a euglycaemic-hyperinsulinaemic clamp to measure whole body
      insulin sensitivity. Mitochondria were isolated from skeletal muscle biopsies,
      and mitochondrial ATP synthesis and hydrogen peroxide production were measured ex
      vivo under conditions that maximally stimulate ATP synthesis and ROS production
      using chemiluminescent and fluorescent techniques, respectively. RESULTS:
      Compared with lean controls, both obese non-diabetic and type 2 diabetic
      participants were resistant to insulin, and had a reduced rate of mitochondrial
      ATP production. Obese insulin-resistant participants had a decreased rate of
      mitochondrial ROS production, while ROS production rate in participants with type
      2 diabetes was similar to that in lean healthy participants. In non-diabetic
      participants, the rate of ROS production was strongly correlated with the rate of
      ATP synthesis and the glucose disposal rate measured with the euglycaemic
      hyperinsulinaemic clamp. The ROS/ATP ratio in obese insulin-resistant
      participants was similar to that in lean insulin-sensitive participants, while
      the ratio was significantly elevated in type 2 diabetes participants.
      CONCLUSIONS/INTERPRETATION: Since, in absolute terms, the maximal capacity for
      mitochondrial ROS production was not increased in either obese insulin-resistant
      participants or in type 2 diabetic participants, these results do not favour a
      role for increased mitochondrial ROS production in the pathogenesis of insulin
      resistance in human skeletal muscle. However, care should be taken in
      extrapolating these ex vivo observations to the in vivo situation.

PMID- 19183936
TI  - Levels of soluble receptor for AGE are cross-sectionally associated with
      cardiovascular disease in type 1 diabetes, and this association is partially
      mediated by endothelial and renal dysfunction and by low-grade inflammation: the
      EURODIAB Prospective Complications Study.
AB  - AIMS/HYPOTHESIS: Plasma soluble receptor for AGE (sRAGE) may reflect the activity
      of the AGE-RAGE axis, which has been proposed as a potential mechanism linking
      hyperglycaemia to vascular complications in diabetes. We have therefore
      investigated: (1) whether sRAGE is associated with greater prevalence of
      cardiovascular disease (CVD) and microvascular complications in type 1 diabetic
      individuals; and (2) the extent to which any such associations are explained by
      markers of endothelial and renal dysfunction and inflammation. METHODS: The study
      included 477 individuals (234 women; mean age 42 +/- 10 [SD] years) from the
      EURODIAB Prospective Complications Study. We used linear regression analyses to
      investigate the differences in sRAGE levels between individuals with and without
      vascular complications. All analyses were adjusted for age, sex, HbA(1c),
      duration of diabetes and other risk factors. RESULTS: Individuals with CVD (n =
      116) had higher levels of sRAGE than those without CVD or any microvascular
      complications (n = 178): beta = 0.15 (95% CI 0.04-0.27). Further adjustments for
      markers of endothelial (beta = 0.13 [0.02-0.24]) and renal dysfunction (beta =
      0.10 [-0.01, 0.20]) and inflammation (beta = 0.12 [0.01-0.23]) attenuated these
      differences; altogether these variables explained about 50% of the association
      between sRAGE and prevalent CVD. sRAGE levels tended to be higher in the presence
      and across the levels of severity of albuminuria (p for trend = 0.087) and
      retinopathy (p for trend = 0.057); adjustments for endothelial and renal
      dysfunction and inflammation also attenuated these differences.
      CONCLUSIONS/INTERPRETATION: sRAGE is associated with greater prevalence of CVD in
      type 1 diabetic individuals, and these associations may be partly explained by
      endothelial and renal dysfunction and low-grade inflammation.

PMID- 19183937
TI  - Ambulatory pulse pressure, decreased nocturnal blood pressure reduction and
      progression of nephropathy in type 2 diabetic patients.
AB  - AIMS/HYPOTHESIS: We followed type 2 diabetic patients over a long period to
      evaluate the predictive value of ambulatory pulse pressure (PP) and decreased
      nocturnal BP reduction (non-dipping) for nephropathy progression. METHODS: Type 2
      diabetic patients (n = 112) were followed for an average of 9.5 (range 0.5-14.5)
      years. At baseline, all patients underwent 24 h ambulatory BP measurement.
      Urinary albumin excretion rate was evaluated by three urinary albumin:creatinine
      ratio measurements at baseline and follow-up. RESULTS: At baseline, patients who
      subsequently progressed to a more advanced nephropathy stage (n = 35) had reduced
      diastolic night/day BP variation and higher 24 h systolic BP and PP values; they
      also had more advanced nephropathy and were more likely to smoke than those with
      no progression of nephropathy (n = 77). In a Cox regression analysis, independent
      predictors of nephropathy progression were 24 h PP (p < 0.01), diastolic
      night:day BP ratio (p = 0.02) and smoking (p = 0.02). The adjusted hazards ratio
      (95% CI) for each mmHg increment in 24 h PP was 1.04 (1.01-1.07), whereas the
      adjusted hazards ratio (95% CI) for each 1% increase in diastolic night:day BP
      ratio was 1.06 (1.01-1.11). Only one of 33 patients (3.0%) with both a diastolic
      night:day BP ratio and a 24 h PP below the median progressed, whereas 17 of 32
      patients (53.1%) with both a diastolic night:day BP ratio and a 24 h PP equal to
      or above the median progressed to a more advanced nephropathy stage (p < 0.001).
      CONCLUSIONS/INTERPRETATION: Ambulatory PP, impaired nocturnal BP decline and
      smoking are strong, independent predictors of nephropathy progression in type 2
      diabetic patients.

PMID- 19183938
TI  - Differentiation of COPAS-sorted non-endocrine pancreatic cells into insulin
      positive cells in the mouse.
AB  - AIMS/HYPOTHESIS: The regenerative process in the pancreas is of particular
      interest, since insulin-producing beta cells are lost in diabetes.
      Differentiation of new beta cells from pancreatic non-endocrine cells has been
      reported in vivo and in vitro, a finding that implies the existence of pancreatic
      stem/progenitor cells. However, while tissue-specific stem cells are well
      documented in skin, intestine and testis, pancreatic stem cells have been
      elusive. We hypothesised that pancreatic stem/progenitor cells within the non
      endocrine fraction could be a source of new islets in vitro. METHODS: To test if
      there were such cells within the pancreas, we generated pancreatic cell
      aggregates from tissue remaining after islet isolation from mouse insulin
      promoter 1-green fluorescent protein (MIP-GFP) mice. To eliminate any
      contamination of insulin-positive cells, we deleted all GFP-positive aggregates
      using COPAS Select and cultured with Matrigel. Immunohistochemistry, quantitative
      real-time PCR and single-cell nested RT-PCR were performed to confirm formation
      of insulin-producing cells. RESULTS: The GFP-negative cells were expanded as
      monolayers and then differentiated into three-dimensional cystic structures.
      After 1 week of culture, GFP-positive cells were found as clusters or single
      cells. By quantitative real-time PCR, no insulin mRNA was detected immediately
      after COPAS sorting, but after differentiation insulin mRNA of the whole
      preparation was 1.91 +/- 0.31% that of purified MIP-GFP beta cells. All GFP
      positive cells expressed insulin 1; most expressed insulin 2, pancreas duodenum
      homeobox-1 and cytokeratin 19 by single cell nested RT-PCR.
      CONCLUSIONS/INTERPRETATION: Our data support the concept that within the exocrine
      (acinar and ductal) pancreas of the adult mouse there are cells that can give
      rise to insulin-positive cells in vitro.

PMID- 19183939
TI  - [Modern scoliosis surgery under the conditions of the German DRG-system].
AB  - In the German health system the payment of a hospital stay is standardised. The
      common basis is the G-DRG System (German diagnosis-related groups) in which every
      stay is paid by a lump sum. Scoliosis correction in our times means pedicle screw
      based multilevel double rod instrumentation or anterior plate-rod instrumentation
      with primary stability. The outcome of those methods has improved the results of
      correction and decreased the complication rate but also means high costs due to
      the implants. Scoliosis correction is covered by DRG I06. Due to constant efforts
      a general improvement took place in the assessment of DRG I06. That is the reason
      why the losses incurred in DRG I06C could be lowered to 38% and in I06D to 22% in
      2008. For an appropriate assessment further improvements are required.

PMID- 19183940
TI  - [Results of treatment of progressive scoliosis with SMA staples].
AB  - Anterior vertebral body stapling is a new minimally invasive technique to correct
      scoliotic deformities without fusion. In the literature only preliminary reports
      with short follow-up periods are available. A total of six patients with a
      minimum follow-up of 2 years were available for examination. Of the six patients
      four demonstrated progression of scoliosis in spite of vertebral body stapling.
      All had curves of more than 35 degrees at the time of surgery, while two patients
      with less extensive curves below 35 degrees did not show signs of progression.
      Major complications were not observed. Vertebral body stapling for curves more
      than 35 degrees does not seem to be indicated and careful patient selection for
      stapling may be indicated for curves less than 35 degrees . A more general use of
      this technique is not recommended at this time.

PMID- 19183941
TI  - Hypercapnia in late-phase ALI/ARDS: providing spontaneous breathing using
      pumpless extracorporeal lung assist.
AB  - OBJECTIVE: The fibroproliferative phase of late ALI/ARDS as described by Hudson
      and Hough (Clin Chest Med 27:671-677, 2006) is associated with pronounced
      reductions in pulmonary compliance and an accompanying hypercapnia complicating
      low tidal volume mechanical ventilation. We report the effects of extracorporeal
      CO(2) removal by means of a novel pumpless extracorporeal lung assist (p-ECLA) on
      tidal volumes, airway pressures, breathing patterns and sedation management in
      pneumonia patients during late-phase ARDS. DESIGN: Retrospective analysis.
      SETTING: Fourteen-bed university hospital ICU. PATIENTS: Ten consecutive late
      phase ALI/ARDS patients with low pulmonary compliance, and severe hypercapnia.
      INTERVENTION: Gas exchange, tidal volumes, airway pressures, breathing patterns
      and sedation requirements before (baseline) and after (2-4 days) initiation of
      treatment with p-ECLA were analysed. Patients were ventilated in a pressure
      controlled mode with PEEP adjusted to pre-defined oxygenation goals. MEASUREMENTS
      AND MAIN RESULTS: Median reduction in pCO(2) was 50% following institution of p
      ECLA. Extracorporeal CO(2) removal enabled significant reduction in tidal volumes
      (to below 4 ml/kg predicted body weight) and inspiratory plateau pressures [30
      (28.5/32.3) cmH(2)O, median 25, 75% percentiles]. Normalization of pCO(2) levels
      permitted significant reduction in the dosages of analgesics and sedatives. The
      proportion of assisted spontaneous breathing increased within 24 h of instituting
      p-ECLA. CONCLUSION: Elimination of CO(2) by p-ECLA therapy allowed reduction of
      ventilator-induced shear stress through ventilation with tidal volumes below 4
      ml/kg predicted body weight in pneumonia patients with severely impaired
      pulmonary compliance during late-phase ARDS. p-ECLA treatment supported control
      of breathing pattern while sedation requirements were reduced and facilitated the
      implementation of assisted spontaneous breathing.

PMID- 19183942
TI  - Controversies in paediatric continuous renal replacement therapy.
AB  - BACKGROUND: Continuous renal replacement therapy (CRRT) is an invaluable means of
      supporting critically ill children with many illnesses, including acute renal
      failure, drug intoxication, inborn errors of metabolism, and multiorgan failure.
      However, the ideal method of applying the technique is unknown. DISCUSSION: The
      indications for initiation of CRRT, mode, dose, and means of anticoagulating the
      circuit to prolong filter life are all subjects of controversy. The formation of
      a prospective, multicentre paediatric CRRT registry has been a major step forward
      but large, randomised trials of the sort that exist in adult medicine are
      lacking. This review describes the basic technique of CRRT, highlights the
      differences between adult and paediatric prescription, and elaborates on the main
      controversies in the application of CRRT in children. CONCLUSIONS: Current
      evidence suggests that early initiation of CRRT before the onset of substantial
      fluid overload, considering continuous haemofiltration in disease states such as
      respiratory failure following stem cell transplantation, and the use of
      continuous haemodialysis and citrate anticoagulation to prolong circuit life may
      be associated with improved outcomes.

PMID- 19183943
TI  - Modeling the effect of time-dependent exposure on intensive care unit mortality.
AB  - PURPOSE: To illustrate modern survival models with focus on the temporal dynamics
      of intensive care data. A typical situation is given in which time-dependent
      exposures and competing events are present. METHODS: We briefly review the
      following established statistical methods: logistic regression, regression models
      for event-specific hazards and the subdistribution hazard. These approaches are
      compared by showing advantages as well as disadvantages. All methods are applied
      to real data from a study of day-by-day ICU surveillance. RESULTS: Standard
      logistic regression ignores the time-dependent nature of the data and is only a
      crude approach. Cumulative hazards and probability plots add important
      information and provide a deep insight into the temporal dynamics. CONCLUSION:
      This paper might help to encourage researchers working in hospital epidemiology
      to apply adequate statistical models to complex medical questions.

PMID- 19183944
TI  - Intraoperative validation of a new system for invasive continuous cardiac output
      measurement.
AB  - OBJECTIVE: Although bolus thermodilution technique for cardiac output (CO)
      measurement has widespread acceptance, new systems are currently available. We
      evaluated a continuous CO system (TruCCOMS, Aortech International Inc.) that
      operates on the thermal conservation principle and we compared it with the
      reference standard transit time flow measurement (TTFM). MATERIALS AND METHODS:
      Nine consecutive cardiac surgery patients were evaluated. After general
      anesthesia and intubation, a TruCCOMS catheter was percutaneously placed in the
      pulmonary artery (PA). After median sternotomy and pericardiotomy, a TTFM probe
      was placed around the main PA. Right ventricular (RV) CO measurements were
      recorded with both TruCCOMS and TTFM at different times: before cardiopulmonary
      bypass (CPB) (T0), during weaning from CPB (T1), and prior to sternal closure
      (T2). Data analysis included paired student t test, Pearson correlation test, and
      Bland-Altman plotting. RESULTS: TruCCOMS CO values were significantly lower at T0
      (TruCCOMS 4.0 +/- 1.0 vs. TTFM 4.5 +/- 1.0 L/min; P < 0.0001) and T1 (TruCCOMS
      3.6 +/- 0.5 vs. TTFM 4.2 +/- 0.7 L/min; P < 0.0001), and comparable at T2
      (TruCCOMS 4.5 +/- 0.7 vs. TTFM 4.6 +/- 0.8 L/min; P = 0.4). Pearson test showed a
      significant correlation between TruCCOMS and TTFM CO measurements (RT0 = 0.9, RT1
      = 0.8, RT2 = 0.6; P < 0.0001). Bland-Altmann plotting showed a bias of -0.53 +/-
      0.43 L (-12%) at T0, -0.64 +/- 0.43 L (-14.5%) at T1, and -0.1 +/- 0.66 L (-0.8%)
      at T2. CONCLUSION: Although TruCCOMS may significantly underestimate CO,
      measurement trends correlate with TTFM. For this reason, a negative trend in RV
      output should trigger more specific diagnostic procedures.

PMID- 19183945
TI  - Statin administration did not influence the progression of lung injury or
      associated organ failures in a cohort of patients with acute lung injury.
AB  - PURPOSE: Preclinical studies suggest that HMG-CoA reductase inhibitors (statins)
      may attenuate organ dysfunction. We evaluated whether statins are associated with
      attenuation of lung injury and prevention of associated organ failure in patients
      with ALI/ARDS. METHODS: From a database of patients with ALI/ARDS, we determined
      the presence and timing of statin administration. Main outcome measures were the
      development and progression of pulmonary and nonpulmonary organ failures as
      assessed by changes in PaO(2)/FiO(2) ratio and Sequential Organ Failure
      Assessment score (SOFA) between days 1 and 7 after the onset of ALI/ARDS.
      Secondary outcomes included ventilator free days, ICU and hospital mortality, and
      lengths of ICU and hospital stay. RESULTS: From 178 patients with ALI/ARDS, 45
      (25%) received statin therapy. From day 1 to day 7, the statin group showed less
      improvement in their PaO(2)/FiO(2) ratio (27 vs. 55, P = 0.042). Ventilator free
      days (median 21 vs. 16 days, P = 0.158), development or progression of organ
      failures (median DeltaSOFA 1 vs. 2, P = 0.275), ICU mortality (20% vs. 23%, P =
      0.643), and hospital mortality (27 vs. 37%, P = 0.207) were not significantly
      different in the statin and non-statin groups. After adjustment for baseline
      characteristics and propensity for statin administration, there were no
      differences in ICU or hospital lengths of stay. CONCLUSION: In this retrospective
      cohort study, statin use was not associated with improved outcome in patients
      with ALI/ARDS. We were unable to find evidence for protection against pulmonary
      or nonpulmonary organ dysfunction.

PMID- 19183946
TI  - Continuous renal replacement therapy amino acid, trace metal and folate clearance
      in critically ill children.
AB  - PURPOSE: We hypothesized continuous veno-venous hemodialysis (CVVHD) amino acid,
      trace metals and folate clearance impacts nutrient balance. METHODS: Critically
      ill children receiving CVVHD were studied prospectively for 5 days. Blood
      concentrations (amino acids, copper, zinc, manganese, chromium, selenium and
      folate) were measured at CVVHD initiation, and Days 2 and 5. CVVHD clearance,
      losses and nutrient balances were calculated on Days 2 and 5. RESULTS: We studied
      15 children aged 7.7 +/- 6.7 years. Nitrogen balance was negative on Days 2 and
      5. Amino acid clearances ranged from 2.8 to 51.1 ml/min per 1.73 m(2). CVVHD
      losses corresponded to 20% of intake. Days 2 and 5 balances were negative for
      selenium, but positive for other trace metals. Folate clearance was 16 ml/min per
      1.73 m(2) on Days 2 and 5 and serum concentrations decreased significantly from
      initiation to Day 5 (P < 0.05). CONCLUSIONS: Nutrient losses by CVHHD may impact
      adequate nutrition provision.

PMID- 19183947
TI  - Effective performance of a new post-operative cardiac resuscitation simulation
      training scheme in the Paediatric Intensive Care Unit.
AB  - OBJECTIVE: This feasibility study aimed to describe and evaluate the
      effectiveness of a novel chest re-opening paediatric resuscitation scenario
      training scheme. METHODS: A novel scheme offering training on specialist skills
      required for post-operative cardiac patients such as chest re-opening and cardiac
      pacing via simulation was described. A prospective audit of the first 23
      consecutive training sessions was conducted to assess the scheme's effectiveness.
      Parameters assessed included timing of chest re-opening or cardiac pacing orders,
      and any delays in carrying out these orders. RESULTS: The median time required
      for the medical team leader to order chest re-opening was 4 min. New medical
      leaders took significantly longer to order chest re-opening than experienced
      medical team leaders (P = 0.02, Mann-Whitney U test). The performance of the team
      in-training deteriorated with the introduction of new members but was correctable
      with serial training. CONCLUSIONS: Effective simulation training integrating
      chest re-opening and cardiac pacing into standard paediatric resuscitation
      guidelines may be achieved without high fidelity simulation equipment.

PMID- 19183948
TI  - Health-related quality of life as a prognostic factor of survival in critically
      ill patients.
AB  - OBJECTIVE: To evaluate whether health-related quality of life prior to admission
      into an intensive care unit (ICU) is a prognostic factor of hospital and 1 year
      mortality. DESIGN: Prospective cohort study. SETTING: Fourteen-bed medical
      surgical ICU. PATIENTS: A total of 377 patients admitted to the ICU for more than
      24 h with 1-year follow-up after discharge from the hospital. INTERVENTION: A
      health-related quality of life (HRQoL) survey was conducted, using the
      questionnaire developed by the "Project for the Epidemiological Analysis of
      Critical Care Patients", to assess patient's quality of life 1 month before ICU
      hospitalization. RESULTS: Hospital mortality was independently associated with
      severity assessed by APACHE II, odds ratio (OR) 1.14 [95% confidence interval
      (CI) 1.08-1.2; P < 0.001], high workload assessed by Nine Equivalents of Nursing
      Manpower Score > 30 OR 3.6 (95% CI 1.4-9.0; P = 0.006), hospital length of stay
      prior to ICU admission of more than 2 days OR 2.6 (95% CI 1.3-5.4; P = 0.008),
      and bad quality of life prior to ICU admission assessed by a HRQoL score > or = 8
      points OR 2.2 (95% CI 1.03-4.5; P = 0.04). Patients who scored > or =8 on the
      HRQoL survey presented a risk of demise 12 months after discharge almost twofold
      that of those who had good previous HRQoL (0-2 points), Hazard Ratio 1.9 (95% CI
      1.3-2.8; P = 0.001). CONCLUSION: Bad quality of life is associated with hospital
      mortality and survival 12 months after hospital discharge.

PMID- 19183949
TI  - Patient-ventilator asynchrony during non-invasive ventilation for acute
      respiratory failure: a multicenter study.
AB  - OBJECTIVE: To determine the prevalence of patient-ventilator asynchrony in
      patients receiving non-invasive ventilation (NIV) for acute respiratory failure.
      DESIGN: Prospective multicenter observation study. SETTING: Intensive care units
      in three university hospitals. METHODS: Patients consecutively admitted to ICU
      were included. NIV, performed with an ICU ventilator, was set by the clinician.
      Airway pressure, flow, and surface diaphragmatic electromyography were recorded
      continuously for 30 min. Asynchrony events and the asynchrony index (AI) were
      determined from visual inspection of the recordings and clinical observation.
      RESULTS: A total of 60 patients were included, 55% of whom were hypercapnic. Auto
      triggering was present in 8 (13%) patients, double triggering in 9 (15%),
      ineffective breaths in 8 (13%), premature cycling 7 (12%) and late cycling in 14
      (23%). An AI > 10%, indicating severe asynchrony, was present in 26 patients
      (43%), whose median (25-75 IQR) AI was 26 (15-54%). A significant correlation was
      found between the magnitude of leaks and the number of ineffective breaths and
      severity of delayed cycling. Multivariate analysis indicated that the level of
      pressure support and the magnitude of leaks were weakly, albeit significantly,
      associated with an AI > 10%. Patient comfort scale was higher in pts with an AI <
      10%. CONCLUSION: Patient-ventilator asynchrony is common in patients receiving
      NIV for acute respiratory failure. Our results suggest that leaks play a major
      role in generating patient-ventilator asynchrony and discomfort, and point the
      way to further research to determine if ventilator functions designed to cope
      with leaks can reduce asynchrony in the clinical setting.

PMID- 19183950
TI  - Determining small intestinal transit time and pathomorphology in critically ill
      patients using video capsule technology.
AB  - PURPOSE: Gastrointestinal motility can be impaired by serious illness or
      medications, compromising enteral feeding in critical care patients. We compared
      small bowel transit time and morphology in neurosurgical critical care (ICU)
      patients with those in healthy subjects. METHODS: We evaluated small intestinal
      transit time, quality of visualization and intestinal morphology in 16 ICU
      patients (Glasgow Coma Scale score from 6 to 14) and 16 healthy ambulatory
      patients. Video data were obtained with PillCam SB capsules (Given Imaging Ltd.,
      Yoqneam, Israel). RESULTS: Transit time was 5.1 h (3.9-7.7) (median [IQR]) in ICU
      and 4.3 (4.1-5.3 h) in ambulatory patients (P = 0.481). Six ICU patients (37%)
      and two ambulatory patients (12%) had pathological findings (ulcers, petechia,
      erosions) (P = 0.10). CONCLUSIONS: Median small bowel transit times in critically
      ill neurosurgical patients were similar to those in ambulatory subjects, although
      transit times were more variable in the critically ill patients.

PMID- 19183951
TI  - A comparison of methods to identify open-lung PEEP.
AB  - PURPOSE: Many methods exist in the literature for identifying PEEP to set in ARDS
      patients following a lung recruitment maneuver (RM). We compared ten published
      parameters for setting PEEP following a RM. METHODS: Lung injury was induced by
      bilateral lung lavage in 14 female Dorset sheep, yielding a PaO(2) 100-150 mmHg
      at F(I)O(2) 1.0 and PEEP 5 cmH(2)O. A quasi-static P-V curve was then performed
      using the supersyringe method; PEEP was set to 20 cmH(2)O and a RM performed with
      pressure control ventilation (inspiratory pressure set to 40-50 cmH(2)O), until
      PaO(2) + PaCO(2) > 400 mmHg. Following the RM, a decremental PEEP trial was
      performed. The PEEP was decreased in 1 cmH(2)O steps every 5 min until 15 cmH(2)O
      was reached. Parameters measured during the decremental PEEP trial were compared
      with parameters obtained from the P-V curve. RESULTS: For setting PEEP, maximum
      dynamic tidal respiratory compliance, maximum PaO(2), maximum PaO(2) + PaCO(2),
      and minimum shunt calculated during the decremental PEEP trial, and the lower
      Pflex and point of maximal compliance increase on the inflation limb of the P-V
      curve (Pmci,i) were statistically indistinguishable. The PEEP value obtained
      using the deflation upper Pflex and the point of maximal compliance decrease on
      the deflation limb were significantly higher, and the true inflection point on
      the inflation limb and minimum PaCO(2) were significantly lower than the other
      variables. CONCLUSION: In this animal model of ARDS, dynamic tidal respiratory
      compliance, maximum PaO(2), maximum PaO(2) + PaCO(2), minimum shunt, inflation
      lower Pflex and Pmci,i yield similar values for PEEP following a recruitment
      maneuver.

PMID- 19183952
TI  - Thenar oxygen saturation measured by near infrared spectroscopy as a noninvasive
      predictor of low central venous oxygen saturation in septic patients.
AB  - OBJECTIVE: To validate thenar oxygen saturation (StO(2)) measured by near
      infrared spectroscopy (NIRS) as a noninvasive estimation of central venous
      saturation (ScvO(2)) in septic patients. DESIGN: Prospective observational study.
      SETTING: A 26-bed medical-surgical intensive care unit at a university-affiliated
      hospital. PATIENTS: Patients consecutively admitted to the ICU in the early phase
      of severe sepsis and septic shock, after normalization of blood pressure with
      fluids and/or vasoactive drugs. MEASUREMENTS: We recorded demographic data,
      severity score, hemodynamic data, and blood lactate, as well as ScvO(2), and
      StO(2) measured simultaneously on inclusion. Patients were divided into two
      groups according to ScvO(2) values: group A, with ScvO(2) < 70%, and group B,
      with ScvO(2) > or = 70%. RESULTS: Forty patients were studied. StO(2) was
      significantly lower in group A than in group B (74.7 +/- 13.0 vs. 83.3 +/- 6.2, P
      0.018). No differences in age, severity score, hemodynamics, vasoactive drugs, or
      lactate were found between groups. Simultaneously measured ScvO(2) and StO(2)
      showed a significant Pearson correlation (r = 0.39, P 0.017). For a StO(2) value
      of 75%, sensitivity was 0.44, specificity 0.93, positive predictive value 0.92,
      and negative predictive value 0.52 for detecting ScvO(2) values lower than 70%.
      CONCLUSIONS: StO(2) correlates with ScvO(2) in normotensive patients with severe
      sepsis or septic shock. We propose a StO(2) cut-off value of 75% as a specific,
      rapid, noninvasive first step for detecting patients with low ScvO(2) values.
      Further studies are necessary to analyze the role of noninvasive StO(2)
      measurement in future resuscitation algorithms.

PMID- 19183953
TI  - Family members of critically ill cancer patients: assessing the symptoms of
      anxiety and depression.
AB  - OBJECTIVE: To determine prevalence and factors associated with symptoms of
      anxiety and depression in family members of critically ill cancer patients.
      DESIGN: Prospective cohort study. SETTING: A 23-bed intensive care unit in a
      tertiary cancer centre. PATIENTS AND PARTICIPANTS: Three hundred consecutive
      families of cancer patients with length of stay >72 h in ICU. INTERVENTION: None.
      MEASUREMENTS AND MAIN RESULTS: The Hospital Anxiety and Depression Scale
      questionnaire and critical care family needs inventory were completed by family
      members. Prevalence of anxiety and depression in family members was 71 and 50.3%,
      respectively. Regarding the patients' disease, family depression was correlated
      with presence of metastasis, whereas hematological malignancies correlated with
      family' anxiety. Anxiety was independently associated with one patient-related
      factor (prolonged mechanical ventilation) and two family-related factors
      (catholic religion and gender). Factors associated with symptoms of depression
      included one patient-related factor (presence of metastasis) and one family
      related factor (gender). CONCLUSIONS: Present findings demonstrated a high
      prevalence of anxiety and depression in critically ill cancer patients' family
      members during an intensive care unit stay.

PMID- 19183955
TI  - Modification of tibial slope after medial opening wedge high tibial osteotomy:
      clinical study and mathematical modelling.
AB  - A prospective non-randomized non-comparative study involved 30 patients who
      underwent a medial opening wedge high tibial osteotomy for medial knee
      osteoarthritis using a specific surgical procedure. The tibial slope was
      calculated pre-operatively and at a mean follow-up of 14 months. A mathematical
      model of the surgical procedure was developed in order to plan the height of the
      medial opening wedge and to predict tibial slope changes. Tibial-slope
      measurements accuracy was good (0.04 degrees +/- 0.92 degrees ). There was no
      significant difference for the mean tibial slope before and after surgery (9.2
      degrees +/- 5.6 degrees vs. 9.1 degrees +/- 5.6 degrees , P = 0.47). There was a
      perfect agreement between the model and the real values for the HKA angle (0.85)
      and the tibial slope (0.98). The surgical technique used did not modify the
      tibial slope. Our mathematical model for pre-operative planning was validated
      with very good accuracy.

PMID- 19183956
TI  - Accidents and injuries in competitive Enduro motorcyclists: a prospective
      analysis.
AB  - The Erzberg Rodeo Motor Enduro race, was analyzed over three consecutive years to
      analyze the risk of sustaining an accident, to determine the kind and site of
      injured body regions and to correlate the incidence of accidents with the site on
      the race track suspiring that most accidents happen at the first- and the last
      third. In this prospective, field study questionnaires were used recoding fallen
      riders. Demographic data, the third of the race track on which the accident
      happened and details of the accident itself like its mechanism were noted. Each
      injured body region was recorded separately and rated according to the
      abbreviated injury scale. Two thousand nine hundred and twenty-three athletes
      started in 3 years in the Erzberg Rodeo; 6% of them had an accident and 94% were
      non-professionals. Overall, the average abbreviated injury scale was 2.8. More
      than 80% of all counted injuries were superficial. Most accidents happened in a
      curve due to the front tire sliding, affecting mostly arm and leg. Overall 67% of
      all accidents happened at day 1 of the race and 41% of all accidents happened in
      the first-third of the race track. Competitive Enduro motorcyclists have a high
      risk of sustaining an accident, but in comparison a low risk of sustaining a
      severe injury. Curves are the predominant site of accidents.

PMID- 19183957
TI  - Healing results of meniscal tears left in situ during anterior cruciate ligament
      reconstruction: a review of clinical studies.
AB  - The presence of peripheral meniscal tears is common at the time of anterior
      cruciate ligament (ACL) reconstruction. Techniques to preserve the maximum amount
      of meniscal tissue include "non operative" management (tear left alone, without
      repair or removal), meniscus repair, partial meniscectomy. There is a lack of
      consensus guidelines about the management of peripheral stable meniscal tears.
      When to remove, let alone or repair? We performed an evidence-based review of the
      outcomes of stable meniscal tears left in situ during ACL surgery, in order to
      assess the effectiveness of this popular procedure. Clinical and anatomical
      results (arthrography or second look arthroscopy) were analyzed. Our literature
      search yielded ten relevant studies (9 level IV, 1 level III). The mean time of
      follow-up was 16 months. Pain or mechanical symptoms related to the medial
      tibiofemoral joint were reported in 0-66% of cases. Subsequent medial
      meniscectomy or repair were performed in 0-33% of cases. Pain or mechanical
      symptoms related to the lateral tibiofemoral joint were reported in 0-18% cases.
      Subsequent lateral meniscectomy or repair were performed in 0-22% cases. A
      complete healing occurred in 50-61% cases for the medial meniscus and in 55-74%
      cases for the lateral meniscus. No definite conclusion can be made with regard to
      these results. The conservative approach is more effective for lateral menisci.
      The rate of bad results for the medial meniscus remains high when a conservative
      treatment is used. For the medial meniscus, repair of stable peripheral tears may
      be always indicated to decrease the risk of postoperative pain or subsequent
      meniscectomy.

PMID- 19183958
TI  - Does soccer participation lead to genu varum?
AB  - Little is known about the relationship between sport participation and body
      adaptations during growth. Our aim was to investigate whether soccer
      participation in youth is associated with the degree of genu varum. The design
      was a retrospective cohort study. Three hundred and thirty-six male soccer
      players, and 458 male non-soccer players (aged from 8 to 18) were recruited and
      included in the study. The intercondylar (IC) or intermalleolar (IM) distance
      were clinically measured with a specifically designed instrument. The results of
      this study revealed a statistically significant increase in degree of genu varum
      in both groups from the age of 14. However, at the age of 16-18 years a
      significant higher degree of genu varum was observed in the soccer players
      compared to the non-soccer players (P = 0.028). Intense soccer participation
      increases the degree of genu varum in males from the age of 16. Since genu varum
      predisposes to injuries, efforts to reduce the development of genu varum in male
      soccer players are warranted.

PMID- 19183959
TI  - A predictive factor for acquiring an ideal lower limb realignment after opening
      wedge high tibial osteotomy.
AB  - Obtaining a correct postoperative limb alignment is an important factor in
      achieving a successful clinical outcome after an opening-wedge high tibial
      osteotomy (OWHTO). To better predict some of the aspects that impact upon the
      clinical outcomes following this procedure, including postoperative correction
      loss and over correction, we examined the changes in the frontal plane of the
      lower limb in a cohort of patients who had undergone OWHTO using radiography.
      Forty-two knees from 33 patients (23 cases of osteoarthritis and 10 of
      osteonecrosis) underwent a valgus realignment OWHTO procedure and were
      radiographically assessed for changes that occurred pre- and post-surgery. The
      mean femorotibial angle (FTA) was found to be 182.1 +/- 2.0 degrees (12 +/- 2.0
      anatomical varus angulation) preoperatively and 169.6 +/- 2.4 degrees (10.4 +/-
      2.4 anatomical valgus angulation) postoperatively. These measurements thus
      revealed significant changes in the weight bearing line ratio (WBL), femoral axis
      angle (FA), tibial axis angle (TA), tibia plateau angle (TP), tibia vara angle
      (TV) and talar tilt angle (TT) following OWHTO. In contrast, no significant
      change was found in the weight bearing line angle (WBLA) after these treatments.
      To assess the relationship between the correction angle and these indexes, 42
      knees were divided into the following three groups according to the postoperative
      FTA; a normal correction group (168 degrees < or = FTA < or = 172 degrees ), an
      over-correction group (FTA < 168 degrees ), and an under-correction group (FTA >
      172 degrees ). There were significant differences in the delta angle [DA;
      calculated as (pre FTA - post FTA) - (pre TV - post TV)] among each group of
      patients. Our results thus indicate a negative correlation between the DA and
      preoperative TA (R(2) = 0.148, p < 0.05). Hence, given that the correction errors
      in our patients appear to negatively correlate with the preoperative TA,
      postoperative malalignments are likely to be predictable prior to surgery.

PMID- 19183960
TI  - Characterization of diverse heterocyclic amine-degrading denitrifying bacteria
      from various environments.
AB  - Although, there have been many published bacterial strains aerobically degrading
      the heterocyclic amine compounds, only one strain to date has been reported to
      degrade pyrrolidine under denitrifying conditions. In this study, denitrifying
      bacteria degrading pyrrolidine and piperidine were isolated from diverse
      geological and ecological origins through selective enrichment procedures. Based
      on the comparative sequence results of 16S rRNA genes, 30 heterocyclic amine
      degrading isolates were grouped into ten distinct phylotypes belonging to the
      genera Thauera, Castellaniella, Rhizobium, or Paracoccus of the phylum
      Proteobacteria. The representative isolates of individual phylotypes were
      characterized by phylogenetic, phenotypic and chemotaxonomical traits, and
      dissimilatory nitrite reductase gene (nirK and nirS). All isolates completely
      degraded pyrrolidine and piperidine under both aerobic and anaerobic conditions.
      The anaerobic degradations were coupled to nitrate reduction. A metabolic pathway
      for the anaerobic degradation of pyrrolidine was proposed on the basis of enzyme
      activities implicated in pyrrolidine metabolism from three isolates. The three
      key pyrrolidine-metabolizing enzymes pyrrolidine dehydrogenase, gamma
      aminobutyrate/alpha-ketoglutarate aminotransferase, and succinic semialdehyde
      dehydrogenase, were induced by heterocyclic amines under denitrifying conditions.
      They were also induced in cells grown aerobically on heterocyclic amines,
      suggesting that the anaerobic degradation of pyrrolidine shares the pathway with
      aerobic degradation.

PMID- 19183961
TI  - The dilemma of cultivated hepatocytes.

PMID- 19183962
TI  - Pharmacological profile of NOP receptors coupled with calcium signaling via the
      chimeric protein G alpha qi5.
AB  - In this study, the Galpha(qi5) protein was used to force the human
      nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor to signal through the
      Ca(2+) pathway in CHO cells. [Ca(2+)](i) levels were monitored using the
      fluorometer FlexStation II and the Ca(2+) dye Fluo 4 AM. Concentration response
      curves were generated with a panel of full and partial agonists, while NOP
      antagonists were assessed in inhibition-response curves. The following rank order
      of potency of antagonists was measured: SB - 612111 > J - 113397 = Trap - 101 >
      or = UFP - 101 > [Nphe1]N/OF Q(1 - 13)NH2 >> naloxone, which is superimposable to
      literature findings. The rank order of potency of full and partial agonists is
      also similar to that obtained in previous studies with the exception of a panel
      of ligands (UFP-112, Ro 64-6198, ZP120, UFP-113) whose potency was relatively low
      in the Galpha(qi5)-NOP receptor calcium assay. Interestingly, these NOP ligands
      are characterized by slow kinetic of interaction with the NOP receptor, as
      demonstrated by bioassay experiments. These results demonstrated that the
      FlexStation II-Galpha(qi5)-NOP receptor calcium assay represents an adequate and
      useful screening for NOP receptor ligands, particularly for antagonists.

PMID- 19183963
TI  - Enhancing effect of heroin on social recognition learning in male Sprague-Dawley
      rats: modulation by heroin pre-exposure.
AB  - RATIONALE: There is evidence that pre-exposure to drugs of abuse can induce
      sensitization to several of their effects. OBJECTIVE: Four experiments were
      conducted to investigate the effect of heroin pre-exposure on modulation of
      memory consolidation as indexed by heroin's action on rate of learning. MATERIALS
      AND METHODS: Male Sprague-Dawley rats were tested on a social recognition
      learning task which assesses changes in investigation during repeated exposure to
      the same rat (habituation training: four sessions) and during exposure to a novel
      rat (dishabituation test). In the first experiment, rats received 0, 0.3, or 1
      mg/kg heroin s.c. immediately following each training session, or 1 mg/kg heroin
      2 h post-training. In experiments 2 and 3, rats received 1 mg/kg heroin post
      training after a 7-day drug-free period from heroin pre-exposure achieved through
      conditioned place preference (1 mg/kg s.c., 1 injection/day x 4 days) or
      intravenous self-administration (0.05 mg/kg/infusion i.v., 3 h/day x 9 days)
      training. In experiment 4, rats received 0, 0.03, 0.3, or 3 mg/kg heroin post
      training after a 7-day drug-free period from a regimen of heroin administration
      (i.e., 1 mg/kg heroin/day s.c. x 7 days) that induced locomotor sensitization.
      RESULTS: Post-training administration of heroin enhanced social recognition
      learning in a dose- and time-dependent manner. Importantly, no regimen of heroin
      pre-exposure significantly altered this effect of heroin. CONCLUSIONS: These
      results do not support the hypothesis that heroin pre-exposure leads to
      sensitization to its effect on memory consolidation of non-drug-related learning.
      However, this requires further testing using alternative heroin pre-exposure
      regimens, a wider range of post-training heroin doses, as well as other types of
      learning tasks.

PMID- 19183964
TI  - The discriminative stimulus effects of N-methyl-D-aspartate glycine-site ligands
      in NMDA antagonist-trained rats.
AB  - RATIONALE: Many N-methyl-D-aspartate (NMDA) antagonists produce phencyclidine
      (PCP)-like side effects that limit their clinical utility. NMDA glycine-site
      antagonists may be less likely to produce these effects than other site-selective
      NMDA antagonists. OBJECTIVES: The objective of the study is to compare the
      discriminative stimulus effects of novel NMDA glycine-site drugs to those of
      channel blocking and competitive NMDA antagonists. MATERIALS AND METHODS: Drug
      discrimination studies were performed in separate groups of rats trained with
      saline vs. PCP (2 mg/kg i.p.) or the competitive antagonist NPC 17742 (4 mg/kg
      i.p.) using a standard two-lever operant conditioning procedure under an FR32.
      RESULTS: Neither the partial glycine-site agonists aminocyclopropane carboxylic
      acid methyl ester and (+)-HA-966 nor the antagonists L701,324; MDL 100,458; MDL
      100,748; MDL 103,371; MDL 104,472; MDL 105,519; MRZ 2/571; MRZ 2/576; and ACEA
      0762 produced >50% PCP-lever selection, though all were tested over a sufficient
      dose range to produce response rate decreasing effects. All of the antagonists,
      except MDL 100,458 and MDL 100,748, were also tested for NPC 17742-like effects,
      producing somewhat more variable results than in PCP-trained rats. ACEA-0762
      produced full substitution for NPC 17742, whereas MDL 105,519 produced no
      substitution. The remaining compounds engendered between 20% and 80% drug-lever
      selection. CONCLUSION: These results provide evidence that NMDA glycine-site
      partial agonists and antagonists generally do not produce discriminative stimulus
      effects similar to those of representative NMDA channel blockers or competitive
      antagonists. This suggests that these NMDA glycine-site antagonists should be
      less likely to produce the undesirable behavioral side effects seen in clinical
      trials with many other NMDA antagonists.

PMID- 19183965
TI  - Tamoxifen disrupts consolidation and retrieval of morphine-associated contextual
      memory in male mice: interaction with estradiol.
AB  - RATIONALE: Tamoxifen (TMX), a selective estrogen receptor modulator, can affect
      cognitive functions of the brain. The conditioned place preference (CPP) paradigm
      involves memory for the association between contextual cues and the rewarding
      properties produced by a drug. OBJECTIVES: The effects of TMX alone and in
      combination with estradiol (E2) on reward-related memory of morphine were
      investigated in adult male mice. MATERIALS AND METHODS: Using an unbiased CPP
      paradigm, the ability of morphine sulfate (0.5-10 mg/kg, s.c.) to produce CPP was
      studied. Afterwards, the effects of TMX (1-10 mg/kg, s.c.) on the acquisition,
      consolidation, and expression of morphine-induced CPP were assessed. We have also
      evaluated the possible effects of s.c. E2 (10-200 mug/kg) and its co
      administration with TMX (10 mg/kg, s.c.) on the consolidation and retrieval of
      morphine-associated contextual memory. RESULTS: (1) Morphine (0.5-10 mg/kg)
      significantly induced CPP in a dose-dependent manner. (2) TMX (10 mg/kg)
      significantly reduced the time spent by mice in the morphine compartment when
      given immediately after each conditioning session (consolidation) or 30 min
      before testing for place preference in the absence of morphine (expression),
      whereas it had no effect when administered 30 min before each training session
      (acquisition). (3) Post-training or pre-testing administration of E2 increased
      morphine-induced CPP in a dose-dependent manner. (4) In addition, concomitant
      administration of E2 with TMX appears to prevent the impairing effect produced by
      TMX. CONCLUSIONS: TMX appears to disrupt consolidation and retrieval of morphine
      associated contextual memory and this impairing effect might be prevented by E2
      treatment.

PMID- 19183966
TI  - Analysing persistent organic pollutants in eggs, blood and tissue of the green
      sea turtle (Chelonia mydas) using gas chromatography with tandem mass
      spectrometry (GC-MS/MS).
AB  - Investigation into persistent organic pollutants (POPs) in sea turtles is an
      important area of conservation research due to the harmful effects of these
      chemicals. However, the analysis of POPs in the green sea turtle (Chelonia mydas)
      has been limited by methods with relatively high limits of detection and high
      costs associated with multiple sample injections into complex arrangements of
      analytical equipment. The present study aimed to develop a method that could
      detect a large number of POPs in the blood, eggs and tissue of C. mydas at trace
      concentrations. A gas chromatography with tandem mass spectrometry (GC-MS/MS)
      method was developed that could report 125 POP compounds to a limit of detection
      of <35 pg g(-1) using a single sample injection. The recoveries of internal
      standards ranged from 30% to 96%, and the standard reference materials were
      reported to within 70% of the certified values. The coefficient of variation of
      ten replicates of pooled egg sample was <20% for all compounds, indicating low
      within-run variation. This GC-MS/MS method is an improvement of previous methods
      for analysing POPs in C. mydas in that more compounds can be reported at lower
      concentrations and the accuracy and precision of the method are sound. This is
      particularly important for C. mydas as they occupy a low trophic level and have
      lower concentrations of POPs. This method is also simple to set up, and there are
      minimal differences in sample preparation for the different tissue types.

PMID- 19183967
TI  - Hydrolysis of 3,4-methylenedioxymethamphetamine (MDMA) metabolite conjugates in
      human, squirrel monkey, and rat plasma.
AB  - Characterizing the formation of metabolites of 3,4-methylenedioxymethamphetamine
      (MDMA, "Ecstasy") in different species (rat, squirrel monkey, and human) may
      provide insight into mechanisms of MDMA neurotoxicity. Two prominent MDMA
      metabolites, 3,4-dihydroxymethamphetamine (HHMA) and 4-hydroxy-3
      methoxymethamphetamine (HMMA), are conjugated with glucuronic or sulfuric acid,
      but reference standards are not available; therefore, quantification is only
      possible after conjugate cleavage. Different concentrations of HHMA and HMMA were
      obtained in human, squirrel monkey, and rat plasma specimens when acid or
      enzymatic cleavage was performed. Our data document that these differences are
      due to species-specific influences on conjugate cleavage. Acidic hydrolysis
      should be used for analyzing free HHMA and HMMA in human or squirrel monkey
      plasma, while enzymatic hydrolysis with glucuronidase or sulfatase maximizes
      recovery of free HHMA and HMMA in rat plasma. Optimization of cleavage conditions
      showed that sulfate conjugates were more readily cleaved by acid hydrolysis and
      glucuronides by glucuronidase.

PMID- 19183968
TI  - Fluorescence properties of selected benzo[c]phenantridine alkaloids and studies
      of their interaction with CT DNA.
AB  - The spectral, especially fluorescence properties, of seven selected quaternary
      benzo[c]phenantridine alkaloids (sanguinarine, chelerythrine, chelirubine,
      sanguirubine, chelilutine, sanguilutine, and macarpine) were studied in presence
      and in absence of double-stranded DNA. This study has proved dramatic differences
      in fluorescence emission of all studied alkaloids in presence of calf thymus DNA
      in comparison to fluorescence of free alkaloids. The most remarkable are changes
      in emission spectra of macarpine, chelirubine, and sanguirubine. Association
      constants (logK) for interaction of all studied alkaloids with CT DNA were
      calculated.

PMID- 19183969
TI  - Impaired distance perception and size constancy following bilateral
      occipitoparietal damage.
AB  - Accurate distance perception depends on the processing and integration of a
      variety of monocular and binocular cues. Dorsal stream lesions can impair this
      process, but details of this neurocognitive relationship remain unclear. Here, we
      tested a patient with bilateral occipitoparietal damage and severely impaired
      stereopsis. We addressed four related questions: (1) Can distance and size
      perception survive limitations in perceiving monocular and binocular cues? (2)
      Are egocentric (self-referential) and allocentric (object-referential) distance
      judgments similarly impaired? (3) Are distance measurements equally impaired in
      peripersonal and extrapersonal space? (4) Are size judgments possible when
      distance processing is impaired? The results demonstrate that the patient's
      lesions impaired both her distance and size perception, but not uniformly. Her
      performance when using an egocentric reference frame was more impaired than her
      performance when using an allocentric reference frame. Likewise, her distance
      judgments in peripersonal space were more impaired than those in extrapersonal
      space. The patient showed partial preservation in size processing of novel
      objects even when familiar size cues were removed.

PMID- 19183970
TI  - Is there a direct link between gaze perception and joint attention behaviours?
      Effects of gaze contrast polarity on oculomotor behaviour.
AB  - Previous studies have found that attention is oriented in the direction of other
      people's gaze suggesting that gaze perception is related to the mechanisms of
      joint attention. However, the role of the perception of gaze direction on joint
      attention has been challenged. We investigated the effects of disrupting gaze
      perception on the orienting of observers' attention, in particular, whether
      orienting to gaze direction is affected by the disruptive effect of negative
      contrast polarity on gaze perception. A dynamic distracting gaze was presented to
      observers performing an endogenous saccadic task. Gaze perception was manipulated
      by reversing the contrast polarity between the sclera and the iris. With positive
      display polarity, eye movement recordings showed shorter saccadic latencies when
      the direction of the instructed saccade matched the direction of the distracting
      gaze, and a substantial number of erroneous saccades towards the direction of the
      perceived gaze when the latter did not match the instruction. Crucially, such
      effects were not found when gaze contrast polarity was reversed and gaze
      perception was impaired. These results extend previous studies by demonstrating
      the existence of a direct link between joint attention and the perception of gaze
      direction, and show how orienting of attention to other people's gaze can be
      suppressed.

PMID- 19183971
TI  - Suppression of EMG activity by subthreshold paired-pulse transcranial magnetic
      stimulation to the leg motor cortex.
AB  - Cortical activity driving a voluntary muscle contraction is inhibited by very low
      intensity transcranial magnetic stimulation (TMS) and is reflected in the
      suppression of the average rectified EMG. This approach offers a method to test
      the contribution of cortical neurons actively involved in a motor task, but
      requires a large number of stimuli (approximately 100) to suitably depress the
      average EMG. Here, we investigated whether two pulses of subthreshold TMS at
      interstimulus intervals (ISIs) ranging between 1 and 12 ms could enhance the
      amount of EMG suppression in the tibialis anterior muscle compared to a single
      pulse. Pairs of subthreshold TMS at an ISI of 7 ms produced the maximum EMG
      suppression that was 42% more than the inhibition elicited using a single pulse.
      In addition, the signal-to-noise ratio of the TMS-induced suppression was further
      increased by a second pulse, delivered 7 ms later. The reduction in the EMG at
      the 7 ms paired-pulse interval occurred without any short-latency excitation
      suggesting that the two stimuli increased the activation of cortical inhibitory
      neurons. Subthreshold paired-pulse TMS at ISIs of 1-3 ms was prone to EMG
      excitation in the period that immediately preceded the inhibition and is
      consistent with the recruitment of short-interval intracortical facilitation
      (SICF). We propose that pairs of subthreshold TMS outside the range of SICF with
      an inter-pulse interval of 7 ms is optimal to inhibit ongoing cortical activity
      during human motor movement.

PMID- 19183972
TI  - Non-visually evoked activity of isthmo-optic neurons in awake, head-unrestrained
      quail.
AB  - Changes in the internal state of the brain may modulate retinal function. In
      birds, most neurons in the isthmo-optic (IO) nucleus project their axons
      topographically into the contralateral retina, and activity in IO neurons
      enhances visual responses of retinal ganglion cells in the target retinal region.
      To elucidate the significance of this pathway, we recorded spikes of IO neurons
      in four awake Japanese quail using an implanted electrode assembly while
      recording unrestrained head movements. The IO neurons fired passively in response
      to visual stimuli in receptive fields and non-visually without visual stimuli or
      eye-head movements. Non-visually evoked activity was observed in the middle of
      eye-head fixation, as well as at about 200 ms before the onset of head saccades.
      Intensity of activity before onset of head saccades depended on the direction of
      motion of subsequent head saccades. Local retinal output may be enhanced by
      centrifugal signals before gaze shifts.

PMID- 19183973
TI  - The influence of experimentally induced pain on shoulder muscle activity.
AB  - Muscle function is altered in painful shoulder conditions. However, the influence
      of shoulder pain on muscle coordination of the shoulder has not been fully
      clarified. The aim of the present study was to examine the effect of
      experimentally induced shoulder pain on shoulder muscle function. Eleven healthy
      men (range 22-27 years), with no history of shoulder or cervical problems, were
      included in the study. Pain was induced by 5% hypertonic saline injections into
      the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects
      performed standardized concentric abduction (0 degrees -105 degrees) at a speed
      of approximately 120 degrees/s, controlled by a metronome. During abduction,
      electromyographic (EMG) activity was recorded by intramuscular wire electrodes
      inserted in two deeply located shoulder muscles and by surface-electrodes over
      six superficially located shoulder muscles. EMG was recorded before pain, during
      pain and after pain had subsided and pain intensity was continuously scored on a
      visual analog scale (VAS). During abduction, experimentally induced pain in the
      supraspinatus muscle caused a significant decrease in activity of the anterior
      deltoid, upper trapezius and the infraspinatus and an increase in activity of
      lower trapezius and latissimus dorsi muscles. Following subacromial injection a
      significantly increased muscle activity was seen in the lower trapezius, the
      serratus anterior and the latissimus dorsi muscles. In conclusion, this study
      shows that acute pain both subacromially and in the supraspinatus muscle
      modulates coordination of the shoulder muscles during voluntary movements. During
      painful conditions, an increased activity was detected in the antagonist
      (latissimus), which support the idea that localized pain affects muscle
      activation in a way that protects the painful structure. Further, the changes in
      muscle activity following subacromial pain induction tend to expand the
      subacromial space and thereby decrease the load on the painful structures.

PMID- 19183974
TI  - Glutathione-S-transferase-P1 I105V polymorphism and response to antenatal
      betamethasone in the prevention of respiratory distress syndrome.
AB  - PURPOSE: The aim of this pilot study was to assess the association between
      polymorphisms in genes that encode for proteins involved in the
      pharmacokinetics/pharmacodynamics of glucocorticoids and the occurrence of
      respiratory distress syndrome (RDS) in preterm infants born to mothers treated
      with a complete course of betamethasone. METHODS: Sixty-two preterm infants were
      enrolled. The C1236T, G2677T, and C3435T polymorphisms in the ABCB1 gene, BclI,
      N363S and ER22/23EK in the NR3C1 gene, I105V in the GST-P1 gene and GST-M1 and
      GST-T1 deletions were analyzed, and their association with the occurrence of RDS
      was assessed. RESULTS: In univariate analysis, the heterozygous and homozygous
      presence of the I105V variant in the GST-P1 gene seemed to confer protection
      against the occurrence of RDS (P = 0.032), while no association for all other
      polymorphisms was observed. In multivariate analysis, selection from the
      reference model of independent variables based on AIC (Akaike information
      criteria) maintained three variables in the model: gestation, C3435T, and GST-P1
      genotype. CONCLUSIONS: Polymorphisms of the GST-P1 gene may influence the effect
      of antenatal steroids on the newborn lung.

PMID- 19183975
TI  - Plasma oxalate level in pediatric calcium stone formers with or without secondary
      hyperoxaluria.
AB  - Plasma oxalate (POx) concentration is significantly elevated in primary
      hyperoxaluria, severe renal failure or ethylene glycol poisoning. In these
      conditions, the degree of hyperoxalemia correlates with the severity of systemic
      calcium oxalate (CaOx) deposition and should be therefore carefully monitored.
      Although secondary hyperoxaluria (secHyOx) is a common finding in pediatric
      patients with kidney stone disease, very little is known about POx in this
      condition. We therefore evaluated POx level in 59 children and adolescence with
      calcium urolithiasis (34 confirmed by CaOx stone analysis and 25 children with a
      strong clinical suspicion of this type of urolithiasis), with or without "mild"
      secHyOx. A control group consisted of 41 healthy sex- and age-matched children.
      We found that POx was significantly increased in children with calcium
      urolithiasis and secHyOx compared to healthy children (9.16 +/- 3.60 vs. 6.42 +/-
      2.53 micromol/l), but that was not the case in children with calcium urolithiasis
      but with normal urinary oxalate excretion (7.12 +/- 3.33 micromol/l). We conclude
      that POx may be slightly increased in some pediatric calcium stone formers with
      secHyOx, probably related to intestinal oxalate hyperabsorption.

PMID- 19183976
TI  - Indications of stented uncomplicated ureteroscopic lithotripsy: a prospective
      randomized controlled study.
AB  - The purpose of our trial was to evaluate whether stents could be eliminated after
      uncomplicated ureteroscopic lithotripsy for ureteral stones and the indications
      of ureteral stent placement. A total of 228 patients underwent uncomplicated
      ureteroscopic intracorporeal lithotripsy. After the procedures, patients without
      marked ureteral edema, polypoid change or stent placement were treated as a
      control group. The other patients were randomized to two groups. Patients were
      followed on the first postoperative day, 6 and 12 weeks, postoperatively. In
      stented cases the stent was removed after 1 week. Outcome measures included
      visual analog scale assessment, postoperative analgesic requirements,
      complications and the stone-free rate. On the first postoperative day the
      symptoms of flank pain, dysuria and frequency were significantly greater in the
      stented group (P < 0.0001). The overall perioperative complication rate,
      including fever, pyuria, flank and loin pain, was 3.3% (3/90) in group 1, 16.9%
      (12/71) in group 2, and 41.8% (28/67) in group 3. We believe that in selected
      patients undergoing ureteroscopy for ureteral stone, stents can be safely
      omitted. Patients without stents have significantly less stent-related symptoms
      and are not at higher risk of complications with smooth ureteral mucosa. When
      there is ureteral edema or polypoid change with pyuria, ureteral stents should be
      indwelled to avoid severe postoperative complications.

PMID- 19183977
TI  - Cynodon dactylon extract as a preventive and curative agent in experimentally
      induced nephrolithiasis.
AB  - Cynodon dactylon (Poaceae family) decoction was used in the treatment of kidney
      stones. However, no scientific study was undertaken so far to demonstrate the
      beneficial effect of the plant. Thus, the aim of the current study is to evaluate
      the effect of Cynodon aqueous extract as a preventive and curative agent in
      experimentally induced nephrolithiasis in a rat model. Ethylene glycol (EG) was
      used in the experiment to induce calcium oxalate (CaOx) deposition into kidneys.
      In preventive protocol, Cynodon decoction was administered in the same day with
      EG to evaluate the ability of the extract to prevent crystal deposition. However,
      in curative protocol, rats were first rendered nephrolithiasic and then the
      extract was administered to assess the ability of the plant to eliminate the pre
      existing crystal deposition. In both protocols, urinary biochemical and other
      variables were measured during the course of the study. Crystalluria and renal
      histology were examined as well. The results showed that, in both protocols, all
      measured variables were similar for both the rat groups. Nevertheless, urinary
      biochemical analysis was apparently unaffected by the extract except oxalate in
      preventive protocol, and calcium, sodium, and potassium in curative protocol
      which were significantly highly excreted in treated rats compared to untreated
      animals. Crystalluria was characterized mostly by the presence of large
      quantities of CaOx monohydrate and CaOx dihydrate particles in untreated rats.
      However, crystalluria was mainly dominated by the presence of CaOx dihydrate
      particles with reduced size. The most apparent beneficial effect of Cynodon
      extract was seen in kidney tissues where reduced levels of CaOx deposition have
      been noticed especially in medullary and papillary sections from treated rats. We
      concluded that C. dactylon extract has beneficial effect in preventing and
      eliminating CaOx deposition into kidneys. Such findings provide a scientific
      explanation for its use in the treatment of kidneys stones.

PMID- 19183978
TI  - Migration of a metal clip into the urinary bladder.
AB  - Migration of metal clips into the urinary tract is rare. We present a case in
      which migration of a metal clip into the urinary bladder occurred after
      retropubic radical prostatectomy. A 75-year-old man, who had undergone retropubic
      radical prostatectomy three years before, presented with painful micturition and
      gross hematuria. Radiography and cystoscopy showed two vesical stones. As
      treatment for these stones, transurethral holmium laser lithotripsy was
      performed. One of the stones had formed around a metal clip that had presumably
      migrated into the urinary bladder. After removal of both stones, the patient was
      able to void freely. In conclusion, it is important to remember that metal clips
      may migrate postoperatively and cause secondary complications. Therefore, metal
      clips should be applied sparingly at the vesicourethral anastomosis during
      retropubic radical prostatectomy.

PMID- 19183979
TI  - Pain in extracorporeal shock wave lithotripsy.
AB  - Pain tolerance has long been identified as a factor influencing successful
      treatment of renal calculi by shock wave lithotripsy (SWL). We aimed to clarify
      which factors directly influence pain tolerance to predict which patients are
      likely to undergo successful treatment. We analysed retrospectively 179 patients
      who received their first SWL for a solitary kidney stone. All patients were on a
      non-opioid analgesia protocol and were treated on an outpatient basis. The target
      was to deliver 4,000 shock waves at an energy level of 4. In total, 53% of
      patients could tolerate the targeted shock wave number and energy and were
      retrospectively allocated into group A. Those who required a reduction in either
      energy levels or shock wave number were allocated in group B. Multivariate and
      univariate analysis showed that female patients, who are young with thin body
      habitus, have lower pain tolerance to SWL.

PMID- 19183980
TI  - Increased protein intake on controlled oxalate diets does not increase urinary
      oxalate excretion.
AB  - High animal protein intake is a risk factor for calcium oxalate stone disease.
      The effect of dietary protein on the urinary excretion of calcium, acid and
      citrate is well established. However, its effect on oxalate excretion is unclear,
      due in part to an inadequate control of dietary oxalate intake in previous
      studies. This relationship warrants clarification due to the proposed important
      role of the metabolism of amino acids in endogenous oxalate synthesis. In this
      study, 11 normal subjects consumed controlled oxalate diets containing 0.6, 1.2
      and 1.8 g protein/kg body weight/day. The analysis of 24 h urine collections
      confirmed that as protein intake increased, urinary calcium and glycolate
      increased and urinary pH and citrate decreased. The increased glycolate excretion
      was due in part to an increased hydroxyproline, but not glycolate consumption.
      Total daily urinary oxalate excretion did not change. When indexed to creatinine
      there was a small but significant decrease in oxalate excretion. This is most
      likely due to hyperfiltration. These results indicate that as dietary protein
      intake increases, the catabolism of diet-derived amino acids is not associated
      with an increased endogenous oxalate synthesis in normal subjects.

PMID- 19183981
TI  - Litre-scale microbial fuel cells operated in a complete loop.
AB  - Using the anode effluent to compensate the alkalinization in a bio-cathode has
      recently been proposed as a way to operate a microbial fuel cell (MFC) in a
      continuous and pH neutral way. In this research, we successfully demonstrated
      that the operation of a MFC without any pH adjustments is possible by completing
      the liquid loop over cathode and anode. During the complete loop operation, a
      stable current production of 23.2 +/- 2.5 A m(-3) MFC was obtained, even in the
      presence of 3.2-5.2 mg O(2) L(-1) in the anode. The use of current collectors and
      subdivided electrical circuitries for relative large 2.5-L-scale MFCs resulted in
      ohmic cell resistances in the order of 1.4-1.7 mOmega m(3) MFC, which were
      comparable to values of ten times smaller MFCs. Nevertheless, the bio-cathode
      activity still needs to be improved significantly with a factor 10-50 in order
      achieve desirable current densities of 1,000 A m(-3) MFC.

PMID- 19183982
TI  - A novel dichloromethane-degrading Lysinibacillus sphaericus strain wh22 and its
      degradative plasmid.
AB  - Dichloromethane (DCM)-degrading bacterium strain wh22 (GenBank accession number
      FJ418643) was isolated and identified as Lysinibacillus sphaericus based on
      standard morphological and physiological properties, cellular fatty acid
      composition, mole percent guanine-cytosine content, and nucleotide sequence
      analysis of enzymatically amplified 16S ribosomal deoxyribonucleic acid. The
      strain also grew on many other halocarbons found in the waste gases of industrial
      effluents, such as 1,2-dichloroethane, chlorobromomethane, methylene bromide,
      1,1,1-trichloroethane, trichloroethylene, and hexachlorobenzene. The strain
      harbored a novel degradative plasmid, pRC11 (48.8 kb). The genes coding for the
      metabolism of DCM were found to be plasmid-borne, and a physical map of the
      plasmid has been established. The purified plasmid was transformed to dcm-
      Escherichia coli DH5 at a rate of 1.65 x 10(5). The transformed cells were able
      to grow on DCM at a concentration of 5-16 mM and can be further used as an
      excellent source for genetic manipulations leading to the construction of
      genetically modified microbial strains or genetically engineered microorganisms.

PMID- 19183983
TI  - Fungal laccases as tools for the synthesis of new hybrid molecules and
      biomaterials.
AB  - Laccase is a ligninolytic enzyme widely distributed in wood-rotting fungi and
      which is also found in a variety of molds and insects as well as some plants and
      bacteria. Its biological roles range from depolmerization of lignin, coal and
      humic acids via the oxidation of various mono- and diaromatic structures, to
      polymerization reactions and pigment formation in microbial cells or spores.
      Apart from its action in catabolic, depolymerizing and polymerizing processes,
      laccases have also been shown to be powerful enzymes for coupling two different
      molecules to create new low-molecular-weight products in high yield. In addition
      to their homomolecular coupling capabilities, laccases are also able to couple a
      hydroxylated aromatic substrate with a nonlaccase substrate of variable structure
      to create new heteromolecular hybrid molecules. Thus, laccases are increasingly
      finding applications in biotechnology in the fields of environment-friendly
      synthesis of fine chemicals and for the gentle derivatization of biologically
      active compounds e.g., antibiotics, amino acids, antioxidants, and cytostatics.
      Finally, oligomerization and polymerization reactions can lead to new homo- or
      heteropolymers and biomaterials. These may be useful in a wide range of
      applications including the production of polymers with antioxidative properties,
      the copolymerizing of lignin components with low-molecular mass compounds, the
      coating of cellulosic cotton fibers or wool, the coloring of hair and leathers,
      or the cross-linking and oligomerization of peptides.

PMID- 19183984
TI  - A fluorescent, genetically engineered microorganism that degrades
      organophosphates and commits suicide when required.
AB  - One way to reduce the potential risk of genetically engineered microorganisms
      (GEMs) to the environment is to use a containment system that does not interfere
      with the performance of the GEM until activated. Such a system can be created by
      inserting a suicide cassette consisting of a toxin-encoding gene controlled by an
      inducible promoter. We constructed a GEM that can degrade organophosphorus
      compounds, emit green fluorescence, and commit suicide when required by putting
      the genes that control these different functions under different promoters. The
      genes for enhanced green fluorescent protein (EGFP) and organophosphorus
      hydrolase (OPH) were cloned downstream of the lambda PL promoter in the plasmid
      pBV220. These genes could be expressed freely as long as the GEM was metabolizing
      because the repressor sequence cIts857 had been deleted. The extracellular
      nuclease gene of Serratia marcescens, without its leader-coding sequence,
      provided the suicide mechanism. This was put under the control of the T7 promoter
      to form a suicide cassette activated by the presence of an environmental signal,
      in this case, arabinose. To improve the reliability of this containment system,
      the suicide cassette was duplicated within the conditional suicide plasmid. The
      plasmid carrying the EGFP and OPH fusion genes and that containing the suicide
      cassette were compatible and coexisted in the same host.

PMID- 19183985
TI  - Shoulder, hip, and knee arthrography needle placement using fluoroscopic
      guidance: practice patterns of musculoskeletal radiologists in North America.
AB  - OBJECTIVE: The aim of this study was to evaluate the range of techniques used by
      radiologists performing shoulder, hip, and knee arthrography using fluoroscopic
      guidance. MATERIALS AND METHODS: Questionnaires on shoulder, hip, and knee
      arthrography were distributed to radiologists at a national radiology meeting. We
      enquired regarding years of experience, preferred approaches, needle gauge,
      gadolinium dilution, and volume injected. For each approach, the radiologist was
      asked their starting and end needle position based on a numbered and lettered
      grid superimposed on a radiograph. RESULTS: Sixty-eight questionnaires were
      returned. Sixty-eight radiologists performed shoulder and hip arthrography, and
      65 performed knee arthrograms. Mean experience was 13.5 and 12.8 years,
      respectively. For magnetic resonance arthrography, a gadolinium dilution of 1/200
      was used by 69-71%. For shoulder arthrography, an anterior approach was preferred
      by 65/68 (96%). The most common site of needle end position, for anterior and
      posterior approaches, was immediately lateral to the humeral cortex. A 22-gauge
      needle was used by 46/66 (70%). Mean injected volume was 12.7 ml (5-30). For hip
      arthrography, an anterior approach was preferred by 51/68 (75%). The most common
      site of needle end position, for anterior and lateral approaches, was along the
      lateral femoral head/neck junction. A 22-gauge needle was used by 53/68 (78%).
      Mean injected volume was 11.5 ml (5-20). For knee arthrography, a lateral
      approach was preferred by 41/64 (64%). The most common site of needle end
      position, for lateral and medial approaches, was mid-patellofemoral joint level.
      A 22-gauge needle was used by 36/65 (56%). Mean injected volume was 28.2 ml (5
      60). CONCLUSION: Arthrographic approaches for the shoulder, hip, and knee vary
      among radiologists over a wide range of experience levels.

PMID- 19183986
TI  - Does running cause metatarsophalangeal joint effusions? A comparison of synovial
      fluid volumes on MRI in athletes before and after running.
AB  - OBJECTIVE: The metatarsophalangeal joints (MTPJ) are the only joints that bear
      weight directly through synovium. The purpose of this study was to determine
      whether there is an association between synovial stresses during running and
      increases in volume of joint fluid. MATERIALS AND METHODS: This was a prospective
      case controlled study (nine healthy athlete volunteers acting as own controls).
      High-resolution coronal 3D T2W magnetic resonance imaging of the MTPJs were
      obtained following 24 h rest and after a 30-min run. The volume of joint fluid in
      each MTPJ (n = 90) was measured by two independent observers using an automated
      propagating segmentation tool. RESULTS: The median volume of synovial fluid in
      the MTPJs at rest was 0.018 ml (inter-quartile range (IQ) range 0.005-0.04) and
      after running 0.019 ml (IQ range 0.005-0.04, p = 0.34, 99% confidence interval
      (CI), 0.330.35). The volume of fluid in the MTPJs of the great toes was
      substantially larger than other toes (0.152 ml at rest, 0.154 ml after exercise,
      p = 0.903). Median volumes decrease from second to fifth MTPJs (0.032-0.007 ml at
      rest and 0.035-0.004 ml after exercise). Subset analysis for each toe revealed no
      significant difference in volumes before and after running (p = 0.39 to p = 0.9).
      The inter-rater reliability for observer measurements was good with an intra
      class correlation of 0.70 (95% CI, 0.60 to 0.78). CONCLUSION: It appears to be
      normal to find synovial fluid, particularly in the MTPJs of the great toes, of
      athletes at rest and after running. There does not appear to be an association
      between moderate distance running and an increase in the volume of synovial
      fluid.

PMID- 19183987
TI  - Imaging the femoral sulcus with ultrasound, CT, and MRI: reliability and
      generalizability in patients with patellar instability.
AB  - OBJECTIVE: Recent advances in surgical intervention for patellar instability have
      led to a need for long-term radiological monitoring. The aim of this study is to
      determine whether or not magnetic resonance imaging (MRI) or ultrasound (US) can
      replace computed tomography (CT) as the standard of care for the evaluation of
      the femoral sulcus. MATERIALS AND METHODS: This was a prospective study comparing
      the reliability of CT, magnetic resonance (MR), and US for measuring the femoral
      sulcus in patients with patellar instability. Twenty-four patients were recruited
      to undergo a CT, MR, and US examination of each knee. Two observers independently
      measured femoral sulcus angles from subchondral bone and hyaline cartilage on two
      occasions. Intraclass correlations and generalizability coefficients were
      calculated to measure the reliability of each of the techniques. Thereafter, two
      observers measured the femoral sulcus angle from ultrasound images recorded by
      two independent operators to estimate interobserver and interoperator
      reliability. RESULTS: Forty-seven knees were examined with CT and US and 44 with
      MRI. The sulcus angle was consistently smaller when measured from subchondral
      bone compared to cartilage (5-7 degrees ). Interobserver reliability for CT, MR,
      and US measurements from subchondral bone were 0.87, 0.80, and 0.82 and from
      cartilage 0.80, 0.81, and 0.50. Generalizability coefficients of measurements
      from subchondral bone for CT, MR, and US were 0.87, 0.76, and 0.81 and for
      cartilage 0.76, 0.73, and 0.05. Most of the variability in the US occurred at
      image acquisition rather than measurement. CONCLUSION: In patients with patellar
      instability, CT and MR are reliable techniques for measuring the femoral sulcus
      angle but US, particularly of the articular cartilage, is not. MR is therefore
      the most suitable tool for longitudinal studies of the femoral sulcus.

PMID- 19183988
TI  - The carpal bones in Poland syndrome.
AB  - OBJECTIVE: Classical Poland syndrome is represented by unilateral aplasia of the
      sternocostal head of the pectoralis major muscle and ipsilateral simple
      syndactyly and brachydactyly. Various classifications of the severity of hand
      involvement have been proposed. Since its initial description, numerous studies
      have been made of the bony, soft tissue, organ, and hematological disturbances.
      However, carpal bone involvement has been largely overlooked. The purpose of this
      study was to evaluate the carpal bones in patients with Poland syndrome from a
      local (Manitoba) cohort as well as those from the literature. MATERIALS AND
      METHODS: Hand radiographs from local patients and cases identified from the
      literature with confirmed Poland syndrome were examined for evidence of carpal
      bone involvement. Only cases with radiographs of adequate quality were included
      in the analysis. Clinical information (including gender and age) was necessary
      for evaluation of bone maturation. In total, seven local patients and 23 patients
      from the literature were evaluated. Ethics approval for study of the local
      patients was obtained by the Research Ethics Board of the University of Manitoba.
      RESULTS: Of the 23 literature patients, 12 patients (52%) had abnormal findings.
      Of the abnormal patients, four of 12 (33%) had carpal fusions, eight of 12 (67%)
      showed disharmonious ossification between the carpal and tubular bones and seven
      of 12 (58%) showed delay of carpal ossification. Of the local cohort, three
      patients were too young to characterize carpal involvement. Of the four remaining
      patients, two (50%) had abnormal carpal morphology, three out of four had
      disharmonious ossification and all four had delay of ossification of carpal
      bones. Carpal fusions, particularly of the scaphoid and trapezium, were common in
      both groups. CONCLUSION: Carpal bone anomalies (delay, disharmony, and/or
      fusions) are frequent in Poland syndrome and can occur in patients with either
      mild or severe hand involvement. Imaging of the unaffected hand is helpful in
      determining the extent of carpal findings.

PMID- 19183989
TI  - Osteoarthritis revisited---again!

PMID- 19183990
TI  - Imaging of chest wall infections.
AB  - A wide variety of infections can affect the chest wall including pyogenic,
      tuberculous, fungal, and some other unusual infections. These potentially life
      threatening disorders are frequent especially among immunocompromised patients
      but often misdiagnosed by physical examination and radiographs. The purpose of
      this article is to describe the clinical and imaging features of these different
      chest wall infections according to the different imaging modalities with emphasis
      on ultrasound (US), computed tomography (CT), and magnetic resonance imaging
      (MRI). The outcome of chest wall infection depends on early diagnosis, severity
      of the immunosuppression, offending organism, and extent of infection. Because
      clinical findings and laboratory tests may be not contributive in
      immunocompromised patients, imaging plays an important role in the early
      detection and precise assessment of the disease. US, CT, and MRI are all useful:
      bone destruction is more accurately detected with CT whereas soft tissue
      involvement are better visualized with US and MRI. CT and US are also used to
      guide percutaneous biopsy and drainage procedures. MR images are helpful in pre
      operative planning of extensive chest wall infections.

PMID- 19183991
TI  - Synovial fold of the posterior shoulder joint capsule.
AB  - PURPOSE: The purpose of the study is to describe, based on shoulder MRI and MR
      arthrography with arthroscopic correlation, a posterior joint capsule fold.
      MATERIALS AND METHODS: A retrospective review of 410 shoulder MRIs and direct MR
      arthrograms with arthroscopic correlation in positive cases (when available) was
      obtained with IRB approval and HIPPA compliance. The study was performed by three
      musculoskeletal radiologists. The criteria utilized to establish the diagnosis of
      posterior synovial fold included: (1) axial T1-weighted (T1W) on MR arthrography
      or axial T2* GRE-weighted on MRI demonstrating rounded thickening of the
      posterior shoulder joint capsule with a thickness at least 2 mm in diameter. (2)
      The posterior synovial fold extends in an oblique craniocaudal direction from the
      posterior-inferior joint capsule adjacent to the posterior-inferior glenoid
      labrum (7 o'clock) and continues superiorly away from the glenoid labrum to the
      posterior-superior joint capsule (11 o'clock). RESULTS: Although uncommon, the
      posterior synovial fold was present in 2% (8/410) of studies reviewed and found
      predominantly in women (75%, 6/8). Four patients had arthroscopic confirmation of
      the posterior synovial fold. A higher percentage of posterior synovial folds were
      observed on shoulder MR arthrography (2.7%, 4/150) than on shoulder MRI (1.5%,
      4/260). CONCLUSION: Although rare, the posterior synovial fold can be recognized
      and should not be confused with a posterior labral tear. Further investigation is
      needed to assess its histologic properties and its clinical significance.

PMID- 19183992
TI  - The posterior transtriceps approach for elbow arthrography: a forgotten
      technique?
AB  - OBJECTIVE: To evaluate the technical feasibility of performing elbow MR
      arthrography via a posterior approach through the triceps. MATERIALS AND METHODS:
      The images of 19 patients with elbow MR arthrography via a posterior transtriceps
      approach were retrospectively studied. The injections were performed by four
      musculoskeletal radiologists, using fluoroscopic guidance and a 22- or 25-gauge
      needle. The fluoroscopic and subsequent MR images were reviewed by two
      musculoskeletal radiologists and evaluated for adequacy of joint capsular
      distention, degree and location of contrast leakage, and presence of gas bubbles.
      RESULTS: The injection was diagnostic in all 19 patients, with a sufficient
      amount of contrast agent seen in the elbow joint. No significant contrast leakage
      occurred in 12 patients who received injections of 8 cc or less of contrast
      agent, but moderate contrast leakage occurred in 6/7 patients who received
      injections of greater than 8 cc. Contrast leakage generally occurred within the
      triceps myotendinous junction. No gas bubbles were identified in the injected
      joints. CONCLUSION: Patients often present for MR arthrography of the elbow with
      medial or lateral elbow pain. Contrast leakage during a radiocapitellar approach
      may complicate evaluation of the lateral collateral ligament or the common
      extensor tendon origin. Transtriceps MR arthrography offers an alternative to the
      more commonly used radiocapitellar approach. With injected volumes not exceeding
      8 cc, the risk of significant contrast leakage is small. An advantage of the
      transtriceps injection is that contrast leakage through the posterior needle
      tract does not interfere with evaluation of the lateral structures.

PMID- 19183993
TI  - The broadening spectrum of osteoporotic vertebral fracture.

PMID- 19183994
TI  - Verrucous carcinoma of the foot and enhancement assessment by MRI.
AB  - Verrucous carcinoma (VC), also known as epithelioma cuniculatum, of the foot is
      an uncommon low-grade squamous cell carcinoma with slow, progressive local
      invasion with minimal dysplasia and low potential for metastasis. We report on a
      case of VC and the enhancement pattern associated with it on magnetic resonance
      (MR) imaging. MR imaging revealed a plantar ulcer with an interesting pattern of
      enhancement at the base of the mass. The interface between the mass and the
      normal stroma exhibited a fine-filamentous pattern of enhancement, analogous to
      teased cotton wool, with impressive correlation to the histological appearance of
      our specimen. It is our opinion that VC could be included in the differential of
      a plantar ulcer associated with a mass that exhibits this enhancement pattern.

PMID- 19183995
TI  - Syllabus for postgraduate specialisation in Nuclear Medicine. 2006/07 update.

PMID- 19183996
TI  - V/Q scintigraphy: alive, well and equal to the challenge of CT angiography.

PMID- 19183997
TI  - Evaluation of a novel radiofolate in tumour-bearing mice: promising prospects for
      folate-based radionuclide therapy.
AB  - PURPOSE: Folate-based radiopharmaceuticals have the potential to be used for
      imaging and therapy of tumours positive for the folate receptor (FR). We describe
      the in vitro and in vivo evaluation of a DOTA-folate conjugate. METHODS:
      Radiolabelling of the DOTA-folate was carried out via standard procedures using
      (111)InCl(3) and (177)LuCl(3), respectively. The distribution coefficient (log D)
      was determined in octanol/PBS (pH 7.4). Tissue distribution was investigated in
      nude mice bearing KB tumour xenografts at different time points after
      administration of (111)In-DOTA-folate (radiofolate 1) or (177)Lu-DOTA-folate
      (radiofolate 2) (1 MBq, 1 nmol per mouse). Pemetrexed (PMX, 400 microg) was
      injected 1 h prior to the radiofolate in order to reduce renal uptake. Images
      were acquired with a SPECT/CT camera 24 h after injection of the radiofolate (40
      50 MBq, 3 nmol per mouse). RESULTS: The hydrophilic character of the DOTA-folate
      was represented by a low log D value (radiofolate 1 -4.21+/-0.11). In vivo,
      maximal tumour uptake was found 4 h after injection (radiofolate 1 5.80+/-0.55%
      ID/g; radiofolate 2 7.51+/-1.25% ID/g). In FR-positive kidneys there was
      considerable accumulation of the radiofolates (radiofolate 1 55.88+/-3.91% ID/g;
      radiofolate 2 57.22+/-11.05% ID/g; 4 h after injection). However, renal uptake
      was reduced by preinjection of PMX (radiofolate 1 9.52+/-1.07% ID/g; radiofolate
      2 13.43+/-0.54% ID/g; 4 h after injection) whereas the tumour uptake was retained
      (radiofolate 1 6.32+/-0.41% ID/g; radiofolate 2 8.99+/-0.43% ID/g; 4 h after
      injection). SPECT/CT images clearly confirmed favourable tissue distribution of
      the novel radiofolates and the positive effect of PMX. CONCLUSION: The
      preliminary requirements for the therapeutic use of the novel DOTA-folate are met
      by its favourable tissue distribution that can be ascribed to its hydrophilic
      properties and combined administration with PMX.

PMID- 19183998
TI  - Serotonin transporter binding with [123I]beta-CIT SPECT in major depressive
      disorder versus controls: effect of season and gender.
AB  - PURPOSE: The serotonin system is undoubtedly involved in the pathogenesis of
      major depressive disorder (MDD). More specifically the serotonin transporter
      (SERT) serves as a major target for antidepressant drugs. There are conflicting
      results about SERT availability in depressed patients versus healthy controls. We
      aimed to measure SERT availability and study the effects of age, gender and
      season of scanning in MDD patients in comparison to healthy controls. METHODS: We
      included 49 depressed outpatients (mean+/-SD 42.3 +/- 8.3 years) with a Hamilton
      depression rating scale score above 18, who were drug-naive or drug-free for
      >or=4 weeks, and 49 healthy controls matched for age (+/-2 years) and sex.
      Subjects were scanned with single photon emission computed tomography (SPECT)
      using [(123)I]beta-CIT. SERT availability was expressed as specific to
      nonspecific binding ratios (BP(ND)) in the midbrain and diencephalon with
      cerebellar binding as a reference. RESULTS: In crude comparisons between patients
      and controls, we found no significant differences in midbrain or diencephalon
      SERT availability. In subgroup analyses, depressed males had numerically lower
      midbrain SERT availability than controls, whereas among women SERT availability
      was not different (significant diagnosis x gender interaction; p = 0.048). In the
      diencephalon we found a comparable diagnosis x gender interaction (p = 0.002) and
      an additional smoking x gender (p = 0.036) interaction. In the midbrain the
      season of scanning showed a significant main effect (p = 0.018) with higher SERT
      availability in winter. CONCLUSION: Differences in SERT availability in the
      midbrain and diencephalon in MDD patients compared with healthy subjects are
      affected by gender. The season of scanning is a covariate in the midbrain. The
      diagnosis x gender and gender x smoking interactions in SERT availability should
      be considered in future studies of the pathogenesis of MDD.

PMID- 19184000
TI  - ESCII-PIVAC meeting "Recent advances in cancer immunotherapy with an emphasis on
      cancer vaccines" held in Athens, 9-11 October 2008.

PMID- 19183999
TI  - Aortic inflammation, as assessed by hybrid FDG-PET/CT imaging, is associated with
      enhanced aortic stiffness in addition to concurrent calcification.
AB  - PURPOSE: To analyse the relationship between: (i) aortic pulse wave velocity
      (PWV), an index of aortic stiffness with strong prognostic significance, and (ii)
      aortic calcification and inflammation, which were quantified by hybrid imaging
      with X-ray computed tomography (CT) and (18)F-fluorodeoxyglucose (FDG) positron
      emission tomography (PET). METHODS: Central aortic (carotid-femoral) and
      peripheral (carotid-brachial and femoral-tibial) PWV were recorded in 26
      patients, who had been routinely referred for dual FDG-PET/CT imaging. RESULTS:
      In univariate analyses, central aortic PWV was strongly linked to the volume of
      calcifications (VCa) and an enhanced FDG activity, when determined by averaging
      standardized uptake values (SUV(max)). By multivariate stepwise analysis
      including age and gender, both VCa (p < 0.0001) and SUV(max) (p < 0.01) were
      significant determinants of PWV explaining 61% and 11% of its variability.
      CONCLUSION: Aortic inflammation, assessed by hybrid FDG-PET/CT imaging, is
      associated with an enhanced aortic stiffness, in addition to the concurrent
      impact of calcifications.

PMID- 19184001
TI  - Activation of tumor-specific T lymphocytes after laser-induced thermotherapy in
      patients with colorectal liver metastases.
AB  - PURPOSE: To asses if laser-induced thermotherapy (LITT) induces a specific
      cytotoxic T cell response in patients treated with LITT for colorectal cancer
      liver metastases. METHODS: Eleven patients with liver metastases of colorectal
      cancer underwent LITT. Blood was sampled before and after LITT. Peripheral T cell
      activation was assessed by an interferon gamma (IFNg) secretion assay and flow
      cytometry. Test antigens were autologous liver and tumor lysate obtained from
      each patient by biopsy. T cells were stained for CD3/CD4/CD8 and IFNg to detect
      activated T cells. The ratio of IFNg positive to IFNg negative T cells was
      determined as the stimulation index (SI). To assess cytolytic activity, T cells
      were co-incubated with human colorectal cancer cells (CaCo) and cytosolic
      adenylate kinase release was measured by a luciferase assay. RESULTS: IFNg
      secretion assay: before LITT SI was 12.73 (+/-4.83) for CD3+, 4.36 (+/-3.32) for
      CD4+ and 3.64 (+/-1.77) for CD8+ T cells against autologous tumor tissue. Four
      weeks after LITT SI had increased to 92.09 (+/-12.04) for CD3+ (P < 0.001), 42.92
      (+/-16.68) for CD4+ (P < 0.001) and 47.54 (+/-15.68) for CD8+ T cells (P < 0.001)
      against autologous tumor tissue. No increased SI was observed with normal liver
      tissue at any time point. Cytotoxicity assay: before LITT activity against the
      respective cancer cells was low, with RLU = 1,493 (+/-1,954.68), whereas after
      LITT cytolytic activity had increased to RLU = 7,260 [+/-3,929.76 (P < 0.001)].
      CONCLUSION: Patients with liver metastases of colorectal cancer show a tumor
      specific cytotoxic T cell stimulation and a significantly increased cytolytic
      activity of CD3+, CD4+ and CD8+ T cells after LITT against an allogenic tumor
      (CaCo cell line).

PMID- 19184002
TI  - Intratumoral injection of alpha-gal glycolipids induces a protective anti-tumor T
      cell response which overcomes Treg activity.
AB  - alpha-Gal glycolipids capable of converting tumors into endogenous vaccines, have
      alpha-gal epitopes (Gal alpha 1-3 Gal beta 1-4GlcNAc-R) and are extracted from
      rabbit RBC membranes. alpha-Gal epitopes bind anti-Gal, the most abundant natural
      antibody in humans constituting 1% of immunoglobulins. alpha-Gal glycolipids
      insert into tumor cell membranes, bind anti-Gal and activate complement. The
      complement cleavage peptides C5a and C3a recruit inflammatory cells and APC into
      the treated lesion. Anti-Gal further opsonizes the tumor cells and targets them
      for effective uptake by recruited APC, via Fc gamma receptors. These APC
      transport internalized tumor cells to draining lymph nodes, and present
      immunogenic tumor antigen peptides for activation of tumor specific T cells. The
      present study demonstrates the ability of alpha-gal glycolipids treatment to
      prevent development of metastases at distant sites and to protect against tumor
      challenge in the treated mice. Adoptive transfer studies indicate that this
      protective immune response is mediated by CD8+ T cells, activated by tumor
      lesions turned vaccine. This T cell activation is potent enough to overcome the
      suppressive activity of Treg cells present in tumor bearing mice, however it does
      not elicit an autoimmune response against antigens on normal cells. Insertion of
      alpha-gal glycolipids and subsequent binding of anti-Gal are further demonstrated
      with human melanoma cells, suggesting that intratumoral injection of alpha-gal
      glycolipids is likely to elicit a protective immune response against
      micrometastases also in cancer patients.

PMID- 19184003
TI  - CD4+ T cell responses to HLA-DP5-restricted wild-type sequence p53 peptides in
      patients with head and neck cancer.
AB  - Wild-type sequence (wt) p53 peptides are attractive candidates for broadly
      applicable cancer vaccines. Evidence has been accumulating which indicates that
      CD4+ Th cells have an important role in generating and maintaining antitumor
      immune responses. To elucidate the nature of CD4+ Th responses to wt p53 epitopes
      in patients with squamous cell carcinoma of the head and neck (SCCHN), peripheral
      blood mononuclear cells (PBMCs) from HLA-DP5+ patients were stimulated with HLA
      DP5-restricted wt p53 peptides, p53(108-122) or p53(153-166), and tested for the
      release of IFN-gamma and IL-5 in ELISPOT assays. Immunohistochemistry for p53
      accumulation in tumors, and ELISA for serum antibodies to p53 were also
      performed. Eleven (57.9%) of 19 HLA-DP5+ patients but none of 5 healthy donors
      had detectable Th1 and/or Th2 responses to wt p53 peptides by ELISPOT assay.
      Among these 11 responding patients, 9 (81.8%) and all 11 (100%) patients had a
      tumor burden and p53 accumulation, respectively. On the other hand, two
      responding patients were in post-operative condition. Interestingly, among nine
      patients with a tumor burden, four patients with early disease showed either Th1
      polarized or mixed Th1/Th2 responses, while five patients with advanced disease
      showed either Th2-polarized or mixed Th1/Th2 responses. Our results suggest that
      wt p53(108-122) and p53(153-166) peptides stimulate both Th1- and Th2-type CD4+ T
      cell responses in patients with SCCHN, and anti-p53 Th responses may persist even
      after surgical resection of the tumor; however, the presence of a tumor and its
      progression may affect the nature of immune responses to wt p53 peptides.

PMID- 19184005
TI  - The extrinsic RNA-sensing pathway for adjuvant immunotherapy of cancer.
AB  - Infection with RNA viruses presents a typical pattern of virus products, double
      stranded RNA (dsRNA), and induces the maturation of antigen-presenting dendritic
      cell (mDC). There are several dsRNA sensors that are differentially distributed
      on the cell membrane and in the cytoplasm and are variably expressed depending on
      the cell type. Among these sensors, TLR3 links to the adaptor TICAM-1 (TRIF),
      which is characterized by its unique multipronged signaling cascades for
      cytokine/chemokine production, apoptosis and autophagy in both immune and tumor
      cells. In the context of mDC maturation, various cellular events are further
      induced in response to dsRNA; these include cross-priming followed by CD8+ CTL
      induction, NK activation and proliferation of CD4+ T cells including Th1, Th2,
      Treg and Th17 cells. In this review, we focus on the potential role of dsRNA in
      modulating the inflammatory milieu around mDCs and tumor-associated antigens to
      drive specific cellular effectors against the tumor.

PMID- 19184004
TI  - Amyloid precursor-like protein 2 association with HLA class I molecules.
AB  - Amyloid precursor-like protein 2 (APLP2) is a ubiquitously expressed protein. The
      previously demonstrated functions for APLP2 include binding to the mouse major
      histocompatibility complex (MHC) class I molecule H-2K(d) and down regulating its
      cell surface expression. In this study, we have investigated the interaction of
      APLP2 with the human leukocyte antigen (HLA) class I molecule in human tumor cell
      lines. APLP2 was readily detected in pancreatic, breast, and prostate tumor
      lines, although it was found only in very low amounts in lymphoma cell lines. In
      a pancreatic tumor cell line, HLA class I was extensively co-localized with APLP2
      in vesicular compartments following endocytosis of HLA class I molecules. In
      pancreatic, breast, and prostate tumor lines, APLP2 was bound to the HLA class I
      molecule. APLP2 was found to bind to HLA-A24, and more strongly to HLA-A2.
      Increased expression of APLP2 resulted in reduced surface expression of HLA-A2
      and HLA-A24. Overall, these studies demonstrate that APLP2 binds to the HLA class
      I molecule, co-localizes with it in intracellular vesicles, and reduces the level
      of HLA class I molecule cell surface expression.

PMID- 19184006
TI  - Toll-like receptor expression in normal ovary and ovarian tumors.
AB  - Recent studies have implicated inflammation in the initiation and progression of
      ovarian cancer, though the mechanisms underlying this effect are still not clear.
      Toll-like receptors (TLRs) allow immune cells to recognize pathogens and to
      trigger inflammatory responses. Tumor cell expression of TLRs can promote
      inflammation and cell survival in the tumor microenvironment. Here we sought to
      characterize the expression of TLRs in normal human ovaries, benign and malignant
      ovarian tumors from patients, and in established ovarian tumor cell lines. We
      report that TLR2, TLR3, TLR4, and TLR5 are strongly expressed on the surface
      epithelium of normal ovaries. In contrast to previous studies of uterus and
      endocervix, we found no cyclic variation in TLR expression occurred in murine
      ovaries. TLR2, TLR3, TLR4, and TLR5 are expressed in benign conditions,
      epithelial tumors, and in ovarian cancer cell lines. Variable expression of TLR6
      and TLR8 was seen in benign and malignant epithelium of some patients, while
      expression of TLR1, TLR7, and TLR9 was weak. Normal and malignant ovarian stroma
      were negative for TLR expression. Vascular endothelial cells, macrophages, and
      occasional fibroblasts in tumors were positive. Functional activity for TLRs was
      demonstrated by stimulation of cell lines with specific ligands and subsequent
      activation and translocation of NFkappaB and release of the proinflammatory
      cytokines interleukin-6 and CCL-2. These studies demonstrate expression of
      multiple TLRs in the epithelium of normal ovaries and in ovarian tumor cells, and
      may indicate a mechanism by which epithelial tumors manipulate inflammatory
      pathways to facilitate tumor progression.

PMID- 19184008
TI  - A systematic review of radiological outcomes of highly cross-linked polyethylene
      versus conventional polyethylene in total hip arthroplasty.
AB  - The purpose of this study was to summarise the best evidence to assess
      radiological outcomes of highly cross-linked polyethylene compared with
      conventional polyethylene in total hip arthroplasty. All randomised, controlled
      clinical trials comparing highly cross-linked polyethylene with conventional
      polyethylene were sought and then analysed by two independent reviewers using the
      Cochrane collaboration guidelines. Eight studies in seven articles were
      identified as eligible for inclusion. Due to the clinical and methodological
      heterogeneity, data from the studies included could not be pooled. No failures
      related to highly cross-linked polyethylene were reported. All highly cross
      linked polyethylene groups had a significantly lower wear or penetration than
      conventional polyethylene groups. This preliminary result suggests that highly
      cross-linked polyethylene has significantly less wear than conventional
      polyethylene.

PMID- 19184009
TI  - Recombined bone xenografts enhance tendon graft osteointegration of anterior
      cruciate ligament reconstruction.
AB  - The objective of the study was to discover whether recombined bone xenograft
      (RBX), a porous solid material, could augment healing of the tendon-to-bone
      interface after anterior cruciate ligament (ACL) reconstruction. ACL
      reconstruction was performed bilaterally in 25 skeletally mature rabbits using
      long digital extensor tendon grafts. RBX was implanted into the treated knee,
      with the contralateral knee serving as control. Three rabbits were killed at
      postoperative weeks two, six and 12 for routine histology. The remaining 16
      rabbits were killed at weeks six and 12, and their femur-graft-tibia complexes
      were harvested for mechanical testing. The treatment and control groups produced
      different histological findings at the interface between the tendon and bone. In
      the treatment group, large areas of chondrocyte-like cells were noted around the
      tendon-bone interface two weeks after the operation. At six weeks, more abundant
      bone formation was observed around the tendon. At 12 weeks, an immature
      neoenthesis structure was seen. In biomechanical evaluation six and 12 weeks
      after the operation, the ultimate strength of tendon in the bone tunnel was
      significantly higher in the treatment group than in the control group. RBX can
      augment the osteointegration of tendon to bone after ACL reconstruction.

PMID- 19184010
TI  - Clinical and radiological mid-term results of the thrust plate prosthesis.
AB  - The purpose of this study was to perform an objective clinical and radiological
      assessment of the thrust plate prosthesis (TPP). Fifty-three prostheses were
      evaluated clinically using the Harris hip score (HHS), visual analog scale (VAS),
      and radiographically before surgery, at the time of discharge, and
      postoperatively after on average of 8.09 (range 4.61-9.93) years. The average HHS
      significantly (p < or = 0.05) improved from 48 (range 18-77) points to 95 (range
      46-100) points. The VAS revealed significant (p < or = 0.05) reduction of pain at
      rest and under load. Radiographic analysis showed a considerable potential for
      osteolysis under the thrust plate. Sixteen prostheses revealed signs of
      radiolucent zones. In general, there was a good clinical outcome with no major
      limitations in function. Radiographic changes under the thrust plate indicate an
      adaptation processes resulting from changed biomechanics. This study suggests
      that the TPP could be a good alternative in total hip replacement in younger
      patients.

PMID- 19184015
TI  - Hemin-induced suicidal erythrocyte death.
AB  - Several diseases, such as malaria, sickle cell disease, and ischemia/reperfusion
      may cause excessive formation of hemin, which may in turn trigger hemolysis. A
      variety of drugs and diseases leading to hemolysis triggers suicidal erythrocyte
      death or eryptosis, i.e., cell membrane scrambling and cell shrinkage. Eryptosis
      is elicited by increased cytosolic Ca(2+) activity and by ceramide. The present
      study explored whether hemin stimulates eryptosis. Cell membrane scrambling was
      estimated from annexin V-binding to phosphatidylserine exposed at the cell
      surface, cell shrinkage from forward scatter in fluorescence-activated cell
      sorter analysis, cytosolic Ca(2+) activity from Fluo3 fluorescence and ceramide
      formation from fluorescence-labeled antibody binding. Exposure to hemin (1-10
      microM) within 48 h significantly increased annexin V-binding, decreased forward
      scatter, increased cytosolic Ca(2+) activity, and stimulated ceramide formation.
      In conclusion, hemin stimulates suicidal cell death, which may in turn contribute
      to the clearance of circulating erythrocytes and thus to anemia.

PMID- 19184016
TI  - Protection of mouse bone marrow from etoposide-induced genomic damage by
      dexrazoxane.
AB  - PURPOSE: The objective of the current investigation is to determine whether non
      toxic doses of the catalytic topoisomerase-II inhibitor, dexrazoxane, have
      influence on the genomic damage induced by the anticancer topoisomerase-II
      poison, etoposide, on mice bone marrow cells. METHOD: The scoring of micronuclei,
      chromosomal aberrations, and mitotic activity were undertaken as markers of cyto-
      and genotoxicity. Oxidative damage markers such as reduced glutathione and lipid
      peroxidation were assessed as a possible mechanism underlying this amelioration.
      RESULTS: Dexrazoxane pre-treatment significantly reduced the etoposide-induced
      micronuclei formation, chromosomal aberrations, and also the suppression of
      erythroblast proliferation in bone marrow cells of mice. These effects were dose
      dependent. Etoposide induced marked biochemical alterations characteristic of
      oxidative stress including enhanced lipid peroxidation and reduction in the
      reduced glutathione level. Prior administration of dexrazoxane ahead of etoposide
      challenge ameliorated these biochemical markers. CONCLUSION: Based on our data
      presented, strategies can be developed to decrease the etoposide-induced genomic
      damage in normal cells using dexrazoxane.

PMID- 19184017
TI  - Doxorubicin-induced mitochondrial dysfunction is secondary to nuclear p53
      activation in H9c2 cardiomyoblasts.
AB  - PURPOSE: Doxorubicin (DOX) is a widely prescribed chemotherapeutic. The
      hypothesis for the present study is that DOX-induced myocyte apoptosis involves
      mitochondrial dysfunction that is a consequence of nuclear DOX effects. METHODS:
      H9c2 myoblasts were incubated with 0, 0.5 and 1 muM DOX and nuclear and
      mitochondrial alterations were determined. RESULTS: Doxorubicin accumulation in
      the nucleus was detected after 3 h treatment, followed by an increase in p53 and
      a decrease in mitochondrial membrane potential. Apoptotic markers, such as
      caspase activation and chromatin condensation were detected after 24 h of DOX
      treatment. Bax and p53 translocation to mitochondria as well as the formation of
      Bax clusters in the cytosol were observed. Importantly, pifithrin-alpha, a p53
      inhibitor, protected against DOX-induced mitochondrial depolarization, caspase
      activation and cell death. CONCLUSION: Mitochondrial dysfunction in H9c2
      myoblasts treated with DOX is a consequence of nuclear p53 activation rather than
      a direct effect of the drug on mitochondria.

PMID- 19184018
TI  - Pro-apoptotic and cytostatic activity of naturally occurring cardenolides.
AB  - PURPOSE: Cardenoliddes are steroid glycosides which are known to exert
      cardiotonic effects by inhibiting the Na(+)/K(+)-ATPase. Several of these
      compounds have been shown also to possess anti-tumor potential. The aim of the
      present work was the characterization of the tumor cell growth inhibition
      activity of four cardenolides, isolated from Periploca graeca L., and the
      mechanisms underlying such an effect. METHODS: The pro-apoptotic and cytostatic
      effect of the compounds was tested in U937 (monocytic leukemia) and PC3 (prostate
      adenocarcinoma). Characterization of apoptosis and cell cycle impairment was
      obtained by cytofluorimetry and WB. RESULTS: Periplocymarin and periplocin were
      the most active compounds, periplocymarin being more effective than the reference
      compound ouabain. The reduction of cell number by these two cardenolides was due
      in PC3 cells mainly to the activation of caspase-dependent apoptotic pathways,
      while in U937 cells to the induction of cell cycle impairment without extensive
      cell death. Interestingly, periplocymarin, at cytostatic but non-cytotoxic doses,
      was shown to sensitize U937 cells to TRAIL. CONCLUSIONS: Taken together, our data
      outline that cardiac glycosides are promising anticancer drugs and contribute to
      the identification of new natural cardiac glycosides to obtain chemically
      modified non-cardioactive/low toxic derivatives with enhanced anticancer potency.

PMID- 19184020
TI  - Vandetanib with FOLFIRI in patients with advanced colorectal adenocarcinoma:
      results from an open-label, multicentre Phase I study.
AB  - PURPOSE: The safety and tolerability of vandetanib (ZACTIMA; ZD6474) plus FOLFIRI
      was investigated in patients with advanced colorectal cancer (CRC). METHODS:
      Patients eligible for first- or second-line chemotherapy received once-daily oral
      doses of vandetanib (100 or 300 mg) plus 14-day treatment cycles of FOLFIRI.
      RESULTS: A total of 21 patients received vandetanib 100 mg (n = 11) or 300 mg (n
      = 10) + FOLFIRI. Combination therapy was well tolerated at both vandetanib dose
      levels. There were no DLTs in the vandetanib 100 mg cohort and one DLT of
      hypertension (CTCAE grade 3) in the 300 mg cohort. The most common adverse events
      were diarrhoea (n = 20), nausea (n = 12) and fatigue (n = 10). Two patients (one
      in each cohort) discontinued vandetanib due to adverse events (rash, 100 mg
      cohort; hypertension, 300 mg cohort). There was no apparent pharmacokinetic
      interaction between vandetanib and FOLFIRI. Preliminary efficacy results included
      two confirmed partial responses in the 100 mg cohort and 9 patients with stable
      disease > or =8 weeks (100 mg, n = 7; 300 mg, n = 2). CONCLUSIONS: Once-daily
      vandetanib (100 or 300 mg) in combination with a standard FOLFIRI regimen was
      generally well tolerated in patients with advanced CRC.

PMID- 19184019
TI  - Characterization of highly stable liposomal and immunoliposomal formulations of
      vincristine and vinblastine.
AB  - PURPOSE: Liposome and immunoliposome formulations of two vinca alkaloids,
      vincristine and vinblastine, were prepared using intraliposomal triethylammonium
      sucroseoctasulfate and examined for their ability to stabilize the drug for
      targeted drug delivery in vivo. METHODS: The pharmacokinetics of both the
      encapsulated drug (vincristine or vinblastine) and liposomal carrier were
      examined in Sprague Dawley rats, and the in vivo drug release rates determined.
      Anti-HER2 immunoliposomal vincristine was prepared from a human anti-HER2/neu
      scFv and studied for targeted cytotoxic activity in cell culture, and antitumor
      efficacy in vivo. RESULTS: Nanoliposome formulations of vincristine and
      vinblastine demonstrated similar pharmacokinetic profiles for the liposomal
      carrier, but increased clearance for liposome encapsulated vinblastine (t (1/2) =
      9.7 h) relative to vincristine (t (1/2) = 18.5 h). Immunoliposome formulations of
      vincristine targeted to HER2 using an anti-HER2 scFv antibody fragment displayed
      a marked enhancement in cytotoxicity when compared to non-targeted liposomal
      vincristine control; 63- or 253-fold for BT474 and SKBR3 breast cancer cells,
      respectively. Target-specific activity was also demonstrated in HER2
      overexpressing human tumor xenografts, where the HER2-targeted formulation was
      significantly more efficacious than either free vincristine or non-targeted
      liposomal vincristine. CONCLUSIONS: These results demonstrate that active
      targeting of solid tumors with liposomal formulations of vincristine is possible
      when the resulting immunoliposomes are sufficiently stabilized.

PMID- 19184021
TI  - Evaluation of the antitumoral effect of dihydrocucurbitacin-B in both in vitro
      and in vivo models.
AB  - AIMS: We evaluated both in vitro and in vivo antitumoral properties of an
      isolated compound from Wilbrandia ebracteata, dihydrocucurbitacin-B (DHCB), using
      B16F10 cells (murine melanoma). MATERIALS AND METHODS: We made use of MTT and
      (3)H-Thymidine assays to investigate the cell viability and cell proliferation,
      flow cytometry analysis to monitor cell cycle and apoptosis, western blot
      analysis to evaluate the expression of cell cycle proteins, imunofluorescence
      analysis and in vivo tumor growth and metastasis. RESULTS: Dihydrocucurbitacin-B
      significantly reduced cell proliferation without important effects on cells
      viability. DHCB lead cells to accumulate in G2/M phases accompanied by the
      appearance of polyploid cells, confirmed by fluorescence assays that demonstrated
      a remarkable alteration in the cell cytoskeleton and formation of binuclear
      cells. Annexin-V-FITC incorporation demonstrated that DHCB did not induce
      apoptosis. About 10 microg/mL DHCB was found to decrease cyclin-A, and especially
      in cyclin-B1. The in vivo experiments showed that DHCB treatment (once a day up
      to 12 days; p.o.) was able to reduce the tumor growth and lung metastasis up to
      83.5 and 50.3%, respectively. CONCLUSIONS: Dihydrocucurbitacin-B reduces cell
      proliferation due to a decrease in the expression of cyclins, mainly cyclin-B1
      and disruption of the actin cytoskeleton, arresting B16F10 cells in G2/M phase.
      Taken together, the in vitro and in vivo experiments suggest that DHCB was
      effective against cancer, however, it remains to be proved if DHCB will be a good
      candidate for drug development.

PMID- 19184022
TI  - [Prognostic and predictive factors of invasive breast cancer: update 2009].
AB  - Prognostic factors supply information on the course of a disease (recurrence-free
      and total survival) and are independent of the therapy. The most important
      prognostic factors are lymph node status, tumor diameter and histological
      differentiation stage, lymph and blood vessel invasion as well as staging,
      factors which can all be determined by pathologists. The Nottingham prognostic
      index (NPI) combines the strongest prognostic factors and according to study
      results is a suitable model for prognosis of breast cancer. Predictive factors
      give prior information on the probability of the response of a tumor to a defined
      therapy and include hormone receptor status, the invasion marker uPA/PAI-1,
      detection of isolated tumor cells, a residual tumor and the histological
      resection border.Prognostic or predictive factors are clinically relevant when
      therapy decisions are made possible by their recognition, which lead to an
      improvement in the total survival, recurrence-free survival or quality of life.
      The international consensus recommendation of St. Gallen 2007 requires the
      following as a basis for risk-adapted therapy decisions: tumor size, stage, age,
      nodal status, hormone receptor status and Her2 overexpression or amplification
      status.

PMID- 19184023
TI  - [Immunohistochemistry in breast pathology: differential diagnosis of epithelial
      breast lesions].
AB  - Proliferative epithelial breast lesions include a wide variety of benign
      hyperplastic and noninvasive neoplastic lesions, as well as invasive carcinomas.
      Mammographically these lesions may show microcalcifications, architectural
      distortions or mass lesions. The task of the pathologist begins with a
      preoperative diagnosis by means of minimally invasive biopsy. His diagnosis forms
      the basis for not only the radiological-pathological correlation diagnosis, but
      also for the management of benign proliferative breast disease lesions, as well
      as therapeutic decisions in the case of malignant lesions.In daily practice,
      immunohistochemistry is the method of choice for clarifying difficult cases. The
      aim of this chapter is to describe the relevant markers in breast pathology and
      to provide an algorithmic approach to different proliferative breast disease
      lesions.

PMID- 19184024
TI  - [Anatomy of the breast].
AB  - The human breast consists of lobes with a luminal glandular and a basal
      myoepithelial layer. Immunofluorescence studies have shown that the breast
      epithelium contains cytokeratin (CK)5/14-positive precursor cells which give rise
      to CK8/18-positive glandular or sm-actin-positive myoepithelial cells. Only some
      of the glandular cells contain estrogen receptors. The luminal epithelium of the
      lobules shows a much higher glandular differentiation than the ductal system.
      Diagnostically important cytokeratins of normal breast epithelium and its
      proliferative epithelial processes include luminal cytokeratins (CK7, CK8 and
      CK18) as markers of glandular differentiation and basal cytokeratins (CK5, CK14
      and CK17) as markers of progenitor cells and early cells of the glandular and
      myoepithelial differentiation pathway. The most important myoepithelial markers
      are currently CD10, SMA, SMM-HC and Calponin.

PMID- 19184025
TI  - [Diagnostics of microcalcifications from minimally invasive biopsies in
      mammography screening: results from the prevalence phase].
AB  - BACKGROUND: In mammography screening programmes carried out according to European
      guidelines, minimally invasive biopsies (MIB) are performed on up to 3% of
      participants. The aim of this study was to analyse the spectrum of
      histopathological findings including B categories in MIBs with
      microcalcifications compared to MIBs without microcalcifications. MATERIAL AND
      METHODS: Prospectively collected histological findings of MIBs taken during the
      period July 2006 to June 2007 were analysed using the Breast Screening Pathology
      Database of the Reference Centre in Munster. RESULTS: Of the 4,326 MIBs
      investigated, 2,161 were benign (B1-B3) whereas 2,165 were malignant (B4-B5)
      resulting in an overall malignancy rate of 50.04%. Of the MIBs 1,809 contained
      microcalcifications and 2,517 did not. Cases with microcalcifications showed a
      different distribution of B categories: B2 was found in 44.5% versus 24.2%, B3 in
      18.2% versus 5.5% and the malignancy rate of cases with microcalcifications was
      36.8% versus 59.5%. Of all cases of ductal carcinoma in situ (DCIS) detected in
      the screening programme, 83.35% were diagnosed in MIBs containing
      microcalcifications. CONCLUSIONS: MIBs containing microcalcifications showed a
      different spectrum of diagnoses, especially higher rates of B3 lesions. Even
      though MIBs without microcalcifications showed a higher overall malignancy rate,
      most cases of DCIS were diagnosed in MIB containing microcalcifications.

PMID- 19184026
TI  - Suppression of a DNA polymerase delta mutation by the absence of the high
      mobility group protein Hmo1 in Saccharomyces cerevisiae.
AB  - The deletion of the gene encoding the high mobility group protein Hmo1 suppresses
      the growth retardation of the DNA pol delta mutation, pol3-14, at the restrictive
      temperature. pol3-14 mutant cells undergo cell cycle arrest, and hmo1Delta
      alleviates the arrest permitting continual division of the double mutant. Bypass
      of cell cycle control occurs with an increased rate of mutation. Both pol3-14 and
      hmo1Delta are mutators and their combination provokes a synergistic rate of CAN1
      mutations. RAD18 controls branches of DNA repair pathways and its deletion also
      suppresses pol3 mutations. Comparing hmo1Delta and rad18Delta suppression of pol3
      14 shows that while both require the presence of RAD52-mediated repair, their
      suppression is independent in that both can suppress in the presence of the
      other. We conclude that hmo1Delta suppression of pol3-14 occurs by a mechanism
      whereby normal controls on DNA integrity are breached and lesions flow into RAD52
      mediated repair and error-prone pathways.

PMID- 19184027
TI  - Functional characterization of ribosomal protein L15 from Saccharomyces
      cerevisiae.
AB  - In this study we provide general information on the little studied eukaryotic
      ribosomal protein rpL15. Saccharomyces cerevisiae has two genes, YRPL15A and
      YRPL15B that could potentially code for yeast rpL15 (YrpL15). YRPL15A is
      essential while YRPL15B is dispensable. However, a plasmid-borne copy of the
      YRPL15B gene, controlled by the GAL1 promoter or by the promoter controlling
      expression of the YRPL15A gene, can functionally complement YrpL15A in yeast
      cells, while the same gene controlled by the authentic promoter is inactive.
      Analysis of the levels of YrpL15B-mRNA in yeast cells shows that the YRPL15B gene
      is inactive in transcription. The function of YrpL15A is highly resilient to
      single and multiple amino acid substitutions. In addition, minor deletions from
      both the N- and C-terminal ends of YrpL15A has no effect on protein function,
      while addition of a C-terminal tag that could be used for detection of plasmid
      encoded YrpL15A is detrimental to protein function. YrpL15A could also be
      replaced by the homologous protein from Arabidopsis thaliana despite almost 30%
      differences in the amino acid sequence, while the more closely related protein
      from Schizosaccharomyces pombe was inactive. The lack of function was not caused
      by a failure of the protein to enter the yeast nucleus.

PMID- 19184028
TI  - The benefits of yoga for rheumatoid arthritis: results of a preliminary,
      structured 8-week program.
AB  - The aim of this study was to measure the effects of a bi-weekly Raj yoga program
      on rheumatoid arthritis (RA) disease activity. Subjects were recruited from among
      RA patients in Dubai, United Arab Emirates by email invitations of the RA
      database. Demographic data, disease activity indices, health assessment
      questionnaire (HAQ), and quality of life (QOL) by SF-36 were documented at
      enrollment and after completion of 12 sessions of Raj yoga. A total of 47
      patients were enrolled: 26 yoga and 21 controls. Baseline demographics were
      similar in both groups. Patients who underwent yoga had statistically significant
      improvements in DAS28 and HAQ, but not QOL. Our pilot study of 12 sessions of
      yoga for RA was able to demonstrate statistically significant improvements in RA
      disease parameters. We believe that a longer duration of treatment could result
      in more significant improvements.

PMID- 19184029
TI  - Characterization of synovial tissue from arthritis patients: a proton magnetic
      resonance spectroscopic investigation.
AB  - Hypoxia may contribute to the pathogenesis of synovitis in rheumatoid arthritis
      (RA). Magnetic resonance spectroscopy (MRS) is a technique that uses
      radiofrequency waves to generate a signal which allows a qualitative and
      quantitative assessment of the biochemical composition of tissue. MRS was used to
      evaluate RA synovial tissue for evidence of hypoxia and anaerobic metabolism.
      Synovial tissue samples obtained from eighteen RA patients and four
      osteoarthritis control patients undergoing total knee replacement were analyzed
      using proton MRS, processed for histopathology and scored for inflammation and
      vascularity. Spectra from severely and mildly inflamed tissue differed in peak
      intensity at regions 1.3 ppm (representing lactic acid and lipid), 3.0 ppm
      (representing creatine), 3.2 ppm (representing choline containing metabolites),
      and 3.8 ppm (representing carbohydrates, possibly glucose). With increasing
      inflammation, the intensities of the peak resonance at 1.3 ppm increased and that
      at 3.8 ppm decreased. The intensities of the 3.8 and 3.0 ppm peaks were reduced
      in highly vascular tissue. Specific MR spectral features reflect the anaerobic
      metabolism that is evident with progressively increasing degrees of RA synovial
      inflammation and vascularity. These features correlate partially with synovial
      histopathology.

PMID- 19184030
TI  - Inflammatory response in patients with active and inactive osteoarthritis.
AB  - In the present study, we have investigated comparatively the inflammatory
      response of patients with active and inactive osteoarthritis. The sera from 31
      healthy individuals, 37 patients with active OA, and 19 patients with inactive OA
      were assayed for TNF-alpha, IL-6, sRANKL, RANTES, and MRP8 using ELISA in order
      to evaluate their potential as markers of disease activity. Also, the spontaneous
      and LSP-induced release of TNF-alpha and IL-6 by peripheral blood neutrophils was
      determined. The activation of OA is associated with elevated TNF-alpha, IL-6, and
      RANTES serum levels while sRANKL and MRP8 appeared to be increased in both active
      and inactive OA. The neutrophil spontaneous and up-regulated by LPS cytokine
      release can contribute to the exacerbation of OA.

PMID- 19184031
TI  - Portal vein thrombosis in a patient with hepatitis C virus-related cirrhosis
      complicated with antiphospholipid syndrome.
AB  - We report a rare case of portal vein thrombosis (PVT) associated with
      antiphospholipid syndrome (APS) and hepatitis C virus-related cirrhosis. A 59
      year-old woman with hepatitis C virus (HCV) infection was admitted because of
      coma. The blood test showed a typically cirrhosis pattern including an elevated
      serum ammonia level. Abdominal computed tomography showed liver cirrhosis and
      thrombus in the right branch of the portal vein. To elucidate the cause of PVT,
      antiphospholipid antibodies were examined. Both IgG anti-cardiolipin antibody
      (ELISA) and IgG anti-cardiolipin-beta2 -glycoprotein I complex antibody (ELISA)
      were positive. When PVT is detected in a patient with cirrhosis, it might be
      necessary to examine antiphospholipid antibodies to clarify the cause of PVT.

PMID- 19184032
TI  - Antibody against mutated citrullinated vimentin: a new sensitive marker in the
      diagnosis of rheumatoid arthritis.
AB  - The aim of this study was to determine the performance of antibodies against
      mutated citrullinated vimentin (anti-MCV) in comparison with antibodies to cyclic
      citrullinated peptides (anti-CCP) in patients with rheumatoid arthritis (RA).
      Serum levels of anti-MCV and anti-CCP were determined in 193 patients with RA and
      332 controls, and sensitivity and specificity were calculated. In a separate
      analysis of 86 patients, the anti-MCV levels were compared to disease activity.
      Sensitivity of anti-MCV versus anti-CCP was 71.5 and 69.4%, specificity was 81.3
      and 97.6%, respectively. The ROC curves showed higher specificity and an
      advantage of anti-CCP. In seronegative RA patients the sensitivity of anti-MCV
      was superior over anti-CCP. Anti-MCV positivities also occurred in systemic lupus
      erythematosus and Sjoegren's syndrome. In a subgroup of 86 RA patients we found a
      significant correlation between anti-MCV and disease activity. Anti-MCV appears
      to be an important marker for the diagnosis of RA, and correlates also with
      disease activity.

PMID- 19184033
TI  - HLA-Cw*06 class I region rather than MICA is associated with psoriatic arthritis
      in Czech population.
AB  - Psoriatic arthritis (PsA) is a chronic inflammatory joint disease which affects
      patients suffering from psoriasis. The genetic background especially the
      susceptibility loci on the short arm of the chromosome six contribute to PsA
      development. In our study, we looked for the role of the MICA and HLA-Cw genes
      polymorphisms in PsA pathogenesis. We investigated 100 PsA patients and 94
      healthy Czech individuals. We found an association between HLA-Cw*06 and PsA
      namely PsA with psoriasis type I (age of psoriasis onset before 40 years)
      compared to healthy individuals (P (corrected) < 0.05, OR 2.56, CI 95% 1.33-4.76
      and P (corrected) = 0.01, OR 3.03, CI 95% 1.53-5.88, respectively). The MICA-A9
      allele of the transmembrane microsatelite MICA polymorphism occurred more
      frequently in PsA with psoriasis type II group (age of psoriasis onset after 40
      years) than in controls, 58.6 versus 38.0%, respectively however, this finding
      did not reach a statistical significance after correction (P (corrected) =
      0.085).

PMID- 19184034
TI  - MRI of the knee: how do field strength and radiologist's experience influence
      diagnostic accuracy and interobserver correlation in assessing chondral and
      meniscal lesions and the integrity of the anterior cruciate ligament?
AB  - Accuracy of MRI reports is taken for granted. In this paper the inter-observer
      reliability in the interpretation of meniscal lesions, degree of chondropathy,
      and integrity of the ACL was analyzed while taking the radiologist's experience
      and field strength into account. Fifty-two MRI studies of knees were interpreted
      by 11 radiologists independently. Twenty-two were acquired on 1.0-T, 20 on 1.5-T,
      and 10 on 3.0-T systems. Four of the radiologists had more than 5 years and seven
      had 3 to 5 years of experience in interpreting MRI studies. The findings were
      compared with the intra-operative findings. Inter-observer variance, specificity,
      and sensitivity were evaluated for each field strength. Inter-observer
      correlation ranged between 0.370 for cartilage lesions and 0.597 for meniscal
      tears. Correlation values did not increase with experience or field strength. The
      number of false reports was dependent on the observer, but not on field strength.
      The rate of false interpretations was significantly higher for most criteria in
      the less experienced group. In conclusion, inter-observer correlation was low,
      although the diagnostic criteria were defined. The use of the classification
      scheme should be standardized by uniform training. Radiologist experience seems
      to be more important than field strength.

PMID- 19184035
TI  - Microstructural callosal abnormalities in normal-appearing brain of children with
      developmental delay detected with diffusion tensor imaging.
AB  - Callosal fibres play an important role in psychomotor and cognitive functions.
      The purpose of this study was to investigate possible microstructural
      abnormalities of the corpus callosum in children with developmental delay, who
      have normal conventional brain MR imaging results. Seventeen pediatric patients
      (aged 1-9 years) with developmental delay were studied. Quantitative T2 and
      fractional anisotropy (FA) values were measured at the genu and splenium of the
      corpus callosum (CC). Fibre tracking, volumetric determination, as well as fibre
      density calculations of the CC were also carried out. The results were compared
      with those of the age-matched healthy subjects. A general elevation of T2
      relaxation times (105 ms in patients vs. 95 ms in controls) and reduction of the
      FA values (0.66 in patients vs. 0.74 in controls) at the genu of the CC were
      found in patients. Reductions of the fibre numbers (5,464 in patients vs. 8,886
      in controls) and volumes (3,415 ml in patients vs. 5,235 ml in controls) of the
      CC were found only in patients older than 5 years. The study indicates that
      despite their inconspicuous findings in conventional MRI microstructural brain
      abnormalities are evident in these pediatric patients suffering from
      developmental delay.

PMID- 19184036
TI  - Comparison of sonographically measured bowel wall vascularity, histology, and
      disease activity in Crohn's disease.
AB  - The purposes of this study was to provide a retrospective comparison of
      semiquantitatively measured bowel wall vascularity by power Doppler sonography,
      endoscopic-histopathological biopsy findings, and disease activity in patients
      with confirmed Crohn's disease. Thirty-two out of 1,332 patients with
      histologically confirmed Crohn's disease (18 female, 14 male; mean age 38.8
      years) met the inclusion criteria: ileocolonoscopy with biopsy and power Doppler
      sonographic determination of bowel wall vascularity with assessment of disease
      activity within a period of 5 days. Sonographic determination of bowel wall
      vascularity was based on a semiquantitative score. Endoscopic bowel wall biopsy
      specimens were assessed using a self-developed inflammation score and the disease
      activity was calculated using Crohn's disease activity index (CDAI). A
      significant association (p < 0.05) was shown for results of histology and bowel
      wall vascularity in the terminal ileum (kappa = 0.66; sensitivity 95%;
      specificity 69%). There was no observed association between CDAI and histology,
      although there was an association between CDAI and bowel wall vascularity
      (sensitivity 82%). Increased bowel wall vascularity in the terminal ileum
      measured by power Doppler ultrasound reflects inflammatory activity in
      histologically examined bowel wall. Power Doppler ultrasound may be able to
      monitor activity changes of the bowel wall determined by pharmaceutical
      treatment.

PMID- 19184037
TI  - Accuracy of integrated FDG-PET/contrast-enhanced CT in detecting pelvic and
      paraaortic lymph node metastasis in patients with uterine cancer.
AB  - The purpose is to evaluate the accuracy of integrated (18)F-fluorodeoxyglucose
      (FDG)-positron emission tomography (PET)/computed tomography ((CT) with
      intravenous contrast medium in detecting pelvic and paraaortic lymph node
      metastasis in patients with uterine cancer, with surgical and histopathological
      findings used as the reference standard. Forty-five patients with endometrial or
      uterine cervical cancer underwent radical hysterectomy, including pelvic
      lymphadenectomy with or without paraaortic lymphadenectomy, after PET/CT. PET/CT
      findings were interpreted by two experienced radiologists in consensus. The
      criterion for malignancy on PET/CT images was increased tracer uptake by the
      lymph node, independent of node size. The overall node-based sensitivity,
      specificity, PPV, NPV and accuracy of PET/CT for detecting nodal metastases were
      51.1% (23/45), 99.8% (1,927/1,931), 85.2% (23/27), 98.9% (1,927/1,949) and 98.7%
      (1,950/1,976), respectively. The sensitivity for detecting metastatic lesions 4
      mm or less in short-axis diameter was 12.5% (2/16), that for between 5 and 9 mm
      was 66.7% (16/24), and that for 10 mm or larger was 100.0% (5/5). The overall
      patient-based sensitivity, specificity, positive predictive value ((PPV),
      negative predictive value (NPV), and accuracy were 50% (6/12), 90.9% (30/33),
      66.7% (6/9), 83.3% (30/36) and 80.0% (36/45), respectively. Integrated FDG
      PET/contrast-enhanced CT is superior to conventional imaging, but only moderately
      sensitive in predicting lymph node metastasis preoperatively in patients with
      uterine cancer.

PMID- 19184038
TI  - Feasibility and efficacy of Thulium:YAG laser enucleation (VapoEnucleation) of
      the prostate.
AB  - PURPOSE: Thulium:YAG (Tm:YAG) vaporesection has been introduced and efficiency
      was shown on smaller prostates. Criticism mainly referred to prolonged operation
      time in larger prostates, which appears to be a potential limitation compared to
      HoLEP. Aim of the study was to evaluate feasibility and efficiency of Tm:YAG
      VapoEnucleation in larger prostates. METHODS: VapoEnucleation was performed using
      a 70 W continuous wave-laser. After enucleation tissue was morcellated within the
      bladder. Prospectively assessed outcomes were improvement in urodynamic parameter
      and the intra- and postoperative course. Complications were recorded. RESULTS: A
      total of 88 consecutive patients with prostatic enlargement underwent
      VapoEnucleation. Prostatic volume was 61.3 +/- 24.0 cc (30-160). OR-time was 72
      min +/- 26.6 (35-144) and laser-time 32.4 +/- 10.1 min (16.3-59.3). Applied laser
      energy was 123.7 +/- 40.6 kJ (67.8-240.9). An average of 31.7 +/- 18.3 g of
      tissue was retrieved. Pathology revealed four patients with incidental carcinoma.
      Foley catheter-time was 2 days and the suprapubic tube, if placed, was removed on
      the third postoperative day on average. Twelve complications were recorded,
      including bleeding (3), urinary tract infection (6), second-look procedure, due
      to insufficient deobstruction (2). Re-catherization after successful initial
      voiding trial was necessary in one patient. Mean peak flow rate improved from 3.5
      +/- 4.7 to 19.8 +/- 11.6 ml/s and post-voiding residual urine decreased from
      121.4 +/- 339.9 to 22.4 +/- 32.7 ml. CONCLUSION: The functional outcomes
      demonstrate efficiency of Tm:YAG VapoEnucleation for patients with larger
      prostates. From our experience, learning curve in VapoEnucleation is short and
      complications are minimal. Theoretically, no limitation in prostate size occurs.
      Long-term follow-up is needed to prove durability.

PMID- 19184039
TI  - Flower patterns are adapted for detection by bees.
AB  - We have demonstrated previously that honeybees use brightness vision mediated by
      green (or L-) receptor to detect targets from a long distance. They detect
      circular targets having a dim, for the L-receptor, centre and bright surround
      from a longer distance than targets having bright centre and dim surround. Here
      we show that a majority of bee-pollinated flowers have a centre that, for the L
      receptor, is dim with bright surround, i.e. have patterns that are easy for a bee
      to detect. Flowers with dim for the L-receptor surrounds tend to be larger than
      those with bright surrounds, indicating that flowers compensate for the impaired
      visibility of their patterns by increasing the size of their displays.

PMID- 19184040
TI  - Antennal motor activity induced by pilocarpine in the American cockroach.
AB  - The antennal motor system is activated by the muscarinic agonist pilocarpine in
      the American cockroach Periplaneta americana, and its output patterns were
      examined both in restrained intact animals and in isolated CNS preparations. The
      three-dimensional antennal movements induced by the hemocoelic drug injection
      were analyzed in in vivo preparations. Pilocarpine effectively induced prolonged
      rhythmic movements of both antennae. The antennae tended to describe a spatially
      patterned trajectory, forming loops or the symbol of infinity (infinity). Such
      spatial regularity is comparable to that during spontaneous tethered-walking.
      Rhythmic bursting activities of the antennal motor nerves in in vitro
      preparations were also elicited by bath application of pilocarpine. Cross
      correlation analyses of the bursting spike activities revealed significant
      couplings among certain motor units, implying the spatial regularity of the
      antennal trajectory. The pilocarpine-induced rhythmic activity of antennal motor
      nerves was effectively suppressed by the muscarinic antagonist atropine. These
      results indicate that the activation of the antennal motor system is mediated by
      muscarinic receptors.

PMID- 19184041
TI  - Female reproductive state influences the auditory midbrain response.
AB  - Female behavioral responses to sensory stimuli can be highly variable across the
      reproductive cycle. Female green treefrogs (Hyla cinerea) use the male vocal
      signal to locate and choose a mate. Gravid females approach a vocalizing male to
      mate but do not approach if they have recently mated. Such differences in
      behavioral response may be due in part to shifts in the neural representation of
      auditory information in the brain. In this study, we investigated the influence
      of female reproductive state on neural responses in the auditory midbrain to both
      communication signals (advertisement calls) and non-communication sounds (band
      limited noise bursts). Recently mated females exhibited significantly reduced
      response strengths compared to females not recently mated. Reduced response
      strengths in post-mated females were in response to both noise bursts and male
      advertisement calls but were limited to the lower frequency range corresponding
      to the amphibian papilla of the peripheral auditory system. Our results therefore
      show that the ability of social signals to stimulate the auditory system differs
      in females depending on their reproductive state, and that the differential
      effect on low versus high spectral sensitivities may influence the way the two
      spectral peaks of male advertisement calls are represented.

PMID- 19184042
TI  - Lung respiratory rhythm and pattern generation in the bullfrog: role of
      neurokinin-1 and mu-opioid receptors.
AB  - Location of the lung respiratory rhythm generator (RRG) in the bullfrog brainstem
      was investigated by examining neurokinin-1 and mu-opioid receptor (NK1R, muOR)
      colocalization by immunohistochemistry and characterizing the role of these
      receptors in lung rhythm and episodic pattern generation. NK1R and muOR occurred
      in brainstems from all developmental stages. In juvenile bullfrogs a distinct
      area of colocalization was coincident with high-intensity fluorescent labeling of
      muOR; high-intensity labeling of muOR was not distinctly and consistently
      localized in tadpole brainstems. NK1R labeling intensity did not change with
      development. Similarity in colocalization is consistent with similarity in
      responses to substance P (SP, NK1R agonist) and DAMGO (muOR agonist) when bath
      applied to bullfrog brainstems of different developmental stages. In early stage
      tadpoles and juvenile bullfrogs, SP increased and DAMGO decreased lung burst
      frequency. In juvenile bullfrogs, SP increased lung burst frequency, episode
      frequency, but decreased number of lung bursts per episode and lung burst
      duration. In contrast, DAMGO decreased lung burst frequency and burst cycle
      frequency, episode frequency, and number of lung bursts per episode but increased
      all other lung burst parameters. Based on these results, we hypothesize that NK1R
      and muOR colocalization together with a metamorphosis-related increase in muOR
      intensity marks the location of the lung RRG but not necessarily the lung
      episodic pattern generator.

PMID- 19184043
TI  - Intra-axial dermoid tumor mimicking pilocytic astrocytoma.

PMID- 19184047
TI  - Acute ventriculoperitoneal shunt malfunction following opening of the spinal
      subarachnoid space: a case series.
AB  - INTRODUCTION: Malfunction of cerebrospinal shunts is common and due to multiple
      etiologies. We hypothesize that opening of the spinal dura may prompt shunt
      failure in select individuals with previously unrecognized tenuous shunt
      function. CASE REPORTS: The authors describe five patients with shunted
      hydrocephalus who underwent procedures in which the spinal dura mater was opened.
      All patients had acute dysfunction of their ventriculoperitoneal shunt that
      required shunt revision. All shunt valves were functioning properly at operative
      inspection but all patients were found to have adherent intracranial catheters
      with ingrowth of choroid plexus. CONCLUSIONS: We theorize that the siphoning
      effect caused from cerebrospinal fluid egress from the opened spinal subarachnoid
      space resulted in acute shunt failure. Such alterations in cerebrospinal fluid
      flow may precipitate complete failure of a shunt that is functioning
      suboptimally. Clinicians should be aware that spinal procedures that violate the
      subarachnoid space in shunted hydrocephalic patients may result in acute shunt
      failure. These patients may warrant more careful observation in the early
      postoperative period, particularly as shunt failure may compromise spinal wound
      closures.

PMID- 19184048
TI  - Laparoscopic resection of benign ovarian tumours in children with gonadal
      preservation.
AB  - PURPOSE: Ovarian tumours are often regarded as an indication for open
      oophorectomy, especially following torsion. We wish to report our results of
      laparoscopic ovarian cystectomy with ovarian preservation. METHODS: Retrospective
      review of clinical records of patients who where managed with laparoscopic
      ovarian cystectomy with ovarian preservation. RESULTS: Twelve records were
      identified over a 3-year period. The average age was 11.8 years (9-15).
      Presentation was of a mass in nine patients and torsion in three patients.
      Average size of the mass was 8.2 cm (5-18). Two patients had bilateral lesions.
      All patients were noted to have normal tumour markers. Successful cystectomy with
      ovarian preservation was accomplished in all cases using 3-port laparoscopy. The
      bilateral lesions were addressed at the same surgery with no increased length of
      stay or morbidity. In the three patients with acute torsion, an initial
      laparoscopic detorsion was performed with delayed laparoscopic cystectomy and
      ovarian preservation 7-10 days later. There was one complication of a minor
      umbilical port site infection. Histology was of a mature teratoma in ten cases
      and simple cyst in two. Six patients underwent routine ultrasonographic follow-up
      at 2-5 months at which time the involved ovary assumed a size and shape and blood
      flow comparable to the contra-lateral ovary in five patients. In one patient the
      affected side was smaller, 8.6 ml compared to 10 ml on the contra-lateral ovary.
      The remaining patients have been followed up clinically and remain asymptomatic.
      CONCLUSION: Laparoscopic cystectomy with ovarian preservation can be successfully
      applied to benign ovarian tumours. Acute ovarian torsion is not a
      contraindication to this technique where a two stage procedure still enables us
      to offer ovarian preservation.

PMID- 19184049
TI  - Iopamidol enema treatment for meconium obstruction of prematurity in extremely
      low-birth weight infants: a safe and effective method.
AB  - BACKGROUND/PURPOSE: Meconium obstruction of prematurity (MO) often occurs in
      extremely low-birth weight (ELBW) infants, and its treatment is quite a challenge
      for neonatologists. We attempted to establish a method of primary treatment for
      MO of prematurity in ELBW infants. METHODS: An iopamidol enema with 50 cm H(2)O
      static pressure was performed as the primary treatment. This procedure is safe
      and effective and we recommend this as the first treatment for MO in ELBW
      infants. RESULTS: The procedure was performed 50 times in 23 infants and no
      complications occurred. Out of 23 patients, 20 (88%) improved, but the other 3
      did not. In the failure group, the procedure was performed on a significantly
      later date and the mortality rate was higher (12.5 vs. 67%). CONCLUSIONS: This
      procedure is safe and effective. We recommend this as the first treatment for MO
      in ELBW infants.

PMID- 19184050
TI  - Stroma-predominant Wilms tumor with teratoid features: report of a rare case and
      review of the literature.
AB  - We describe the case of a 4-year-old boy with a unilateral right-sided Wilms
      tumor with stromal predominance and teratoid features, which was localized to the
      kidney and hence, was completely resected. The pediatric surgeon and pathologist,
      both should be aware of this rare appearance of nephroblastoma so as to avoid the
      highly toxic chemotherapy and radiotherapy in such patients.

PMID- 19184051
TI  - Posterior urethral valves: a single center experience over 7 years.
AB  - PURPOSE: To evaluate the outcome of management of 65 consecutive children with
      posterior urethral valves (PUV) using two techniques of valves ablation. METHODS:
      Retrospective review of 65 consecutive children with PUV managed over 7 years.
      There were two groups based on the methods of valves ablation: either Mohan's
      urethral valvotome for primary cases or electrocautery fulguration for patient
      with previous intervention. Serum electrolyte and serial post-void residue (PVR)
      were monitored in outpatient clinic. Alpha-blockers were started in all cases
      with high PVR. Management outcome of patient who had valves ablation with Mohan's
      valvotome were compared with those who had endoscopy fulguration. RESULTS: Sixty
      one patients were regular on follow-up with a median age at presentation of 45
      days. Nineteen (31%) patients were diagnosed antenatally. There were 32 refluxing
      ureters in 26 patients; 58 (95%) underwent primary valve ablation (37 with
      Mohan's urethral valvotome, 21 fulguration). Reflux disappeared in 10 (36%)
      refluxing ureters. There were five (8.2%) urethral strictures (all five in
      fulguration group), eight residual valves (four in each group), and three
      recurrent urinary tract infections. Three patients had nephrectomy and one
      patient had renal transplantation. There was no death. The mean serum creatinine
      for all the patients at presentation and at the last follow-up were 1.2 and 0.5
      mg/dl, respectively (P = 0.031). At follow-up, mean PVR of valvotome group was
      2.5 ml and fulguration group was 2 ml (P = 0.282). The median follow-up period
      was 24 months. CONCLUSIONS: Early ablation of PUV and detailed attention to
      bladder management gives a better outcome. With Mohan's valvotome incidence of
      stricture is less and incidence of residual valves is comparable to endoscopic
      ablation of PUV.

PMID- 19184052
TI  - Do not rush into operating and just observe actively if you are not sure about
      the diagnosis of appendicitis.
AB  - PURPOSE: The aim of this study was to determine whether the admission and active
      observation of children where the diagnosis of acute appendicitis is uncertain is
      a safe and effective way to improve the diagnostic accuracy of appendicitis and
      safely reduce the incidence of negative laparotomies without increasing
      complications. METHODS: We performed a retrospective cohort study of children who
      presented with a complaint of right lower quadrant pain and were hospitalized
      with a diagnosis of appendicitis or suspected appendicitis from 1 January to 31
      December 2007. RESULTS: A total of 569 patients were included in the study. The
      mean age was 9.5 +/- 3.2 (range 1.1-17) years. The number of patients directly
      operated on with a diagnosis of appendicitis was 186 (32%) from the total of 575
      while 389 patients (68%) were observed in the surgical ward as the examination
      and/or investigation findings were equivocal. Of the 383 patients admitted for
      observation, 173 (45%) were operated on with a suspicion of appendicitis after
      14.4 +/- 6.7 h while 210 (55%) were discharged after 1.1 +/- 1.2 days as there
      seemed to have no surgical problem. Our total negative appendectomy rate was 4%
      (14/350) and total perforation rate was 37.4% (131/350). The patients operated on
      directly and those operated on after observation were similar, and there was no
      difference for the preoperative duration of symptom, histopathological diagnosis,
      postoperative complication rate, postoperative inpatient days and hospital
      charges. Total hospitalization duration was significantly longer and the hospital
      charges significantly higher in the negative appendectomy group. CONCLUSION: Both
      the features and results and the complication rates and costs of the group
      operated on after observation were the same as the directly operated on group.
      However, patients undergoing a negative appendectomy stayed as inpatients longer
      than only observation patients with higher treatment charges. We could therefore
      decrease the negative appendectomy rate, the associated cost and duration of
      hospitalization without causing extra complications if we observe and investigate
      patients with right lower quadrant pain with a doubtful diagnosis and did not
      operate on them directly.

PMID- 19184053
TI  - Long-term outcomes of surgery for malignant sacrococcygeal teratoma: 20-year
      experience of a regional UK centre.
AB  - BACKGROUND: The timing of surgery for malignant sacrococcygeal teratoma is
      controversial. The long-term outcomes and complications of surgery for this rare
      tumour are presented. METHODS: All cases of malignant sacrococcygeal teratoma in
      the 20-year period 1987-2006 were identified and the case notes retrieved. The
      age at diagnosis, investigations, presentation, type of surgery, early
      complications, recurrence rates, long-term complications and outcomes were
      recorded. RESULTS: Twelve patients (three males, nine females) were identified.
      Mean age at presentation was 20.8 months (range: 12-39 months). All had the
      Carboplatin-Etoposide-Bleomycin chemotherapeutic protocol. The average time of
      follow-up was 10.6 years (range: 1-17 years). Ten patients had excision of their
      tumours following chemotherapy, whilst two patients had excision prior to
      chemotherapy. Two patients had recurrence of their tumours. There was one death
      (8%), which was due to disseminated metastasis. The other 11 children were all
      well at the last follow-up. CONCLUSION: Surgery for malignant sacrococcygeal
      teratoma is safe and has a low complication rate. The long-term outcomes are
      favourable with minimal side effects.

PMID- 19184054
TI  - Fetus in fetu: two case reports and review of literature.
AB  - Fetus in fetu is a rare disorder. Its embryopathogensis and differentiation from
      teratoma has not been well established. It is a parasitic twin of a diamniotic
      monozygotic twin. Here we report, two cases of fetus in fetu with review of
      literature. In case report 1, a 2-year-old boy was referred for asymptomatic lump
      in abdomen since birth. X-ray showed the mass in the abdomen with some
      calcification and fluid inside. CT scan reported a heterogenous mass in the
      retroperitoneum with bony malformation. CT showed presence of three vertebrae in
      it. After surgically excising the mass and opening the sac it showed presence of
      trunk and two limbs with one of the limbs having a nail. Histopathology showed
      presence of GI tract. In case report 2, 4 month female was found to have lump in
      the abdomen by housemaid while bathing. X-ray showed a soft tissue shadow while
      ultrasonography revealed cystic mass arising from right kidney. CT suggested
      cystic mass with calcification not arising from kidney. During exploration whole
      mass was excised and there was frank fetus inside it. Histopathology confirmed
      presence of four vertebral bodies with germ layers. Although fetus in fetu is
      rare condition, correct diagnosis using imaging can be made before surgery.
      Complete excision is curative.

PMID- 19184055
TI  - The very large recurrent postoperative scrotal hydrocele after pediatric inguinal
      hernia repair: a rare problem.
AB  - PURPOSE: To report the rare problem of a very large recurrent postoperative
      scrotal hydrocele after pediatric inguinal hernia repair. METHODS: From July 1969
      to December 2007 inclusive, the charts of five boys mean age 8 years (range 7
      months-16 years) with very large recurrent postoperative scrotal hydroceles were
      reviewed (Research Ethics Board approval 1000007698). RESULTS: In each case,
      there was a very large recurrent postoperative symptomatic scrotal hydrocele (3
      right, 1 left, 1 bilateral). Their ages at the time of these recurrences were
      between 11 and 16 years; they were repaired within 2-18 months. The first four
      were repaired via a groin incision on finding no recurrent inguinal hernia. The
      last two were repaired through a scrotal approach because a groin ultrasound
      showed no recurrent inguinal hernia. There was 1 second recurrence which was
      successfully repaired. A followup of 1(1/2)-9 years revealed no recurrent
      hydrocele. CONCLUSIONS: The incidence of a very large recurrent symptomatic
      postoperative scrotal hydrocele after repair of a pediatric inguinal hernia is
      0.06% and usually occurs in older boys. If ultrasonography of the groin is normal
      (since a recurrent inguinal hernia seems unlikely in such cases), this repair can
      usually be done via a scrotal approach.

PMID- 19184056
TI  - Relationships between OPG, RANKL, bone metabolism, and bone mineral density in
      biliary atresia.
AB  - PURPOSE: Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B
      ligand (RANKL) have been implicated in osteoclastogenesis. However, the
      relationship between the OPG-RANKL system and bone status in biliary atresia (BA)
      has not, as yet, been clarified. Thus, the aim of this study has been to evaluate
      the relationship between the OPG-RANKL system and bone mineral metabolism in
      patients with BA. METHODS: Fifty patients with BA and 13 healthy controls were
      investigated. The mean age of BA patients and controls was 7.3 +/- 0.6 and 8.0 +/
      1.1 years, respectively. Serum levels of OPG, RANKL, osteocalcin, and C-terminal
      telopeptide of type I collagen (CTX) were measured by sandwich enzyme-linked
      immunosorbent assay. Bone mineral density (BMD) of the lumbar spine was
      determined by dual energy X-ray absorptiometry. RESULTS: Biliary atresia patients
      had significantly elevated serum OPG levels compared with controls (4.0 +/- 0.3
      vs. 3.0 +/- 0.3 pmol/L, P = 0.02) and serum OPG levels in BA patients with
      jaundice were higher than in those without jaundice (4.6 +/- 0.4 vs. 3.6 +/- 0.4
      pmol/L, P = 0.04). Likewise, serum RANKL levels were significantly higher in BA
      patients than in controls (2.9 +/- 0.2 vs. 1.2 +/- 0.7 pmol/L, P = 0.001). In
      addition, serum RANKL levels were increased in BA patients with jaundice compared
      to those without jaundice, but this difference was not statistically significant
      (3.2 +/- 0.3 vs. 2.7 +/- 0.2 pmol/L, P = 0.2). The serum osteocalcin levels in BA
      patients were not significantly different from those in the healthy controls,
      whereas the serum CTX levels were elevated in BA patients compared with the
      controls (0.4 +/- 0.1 vs. 0.2 +/- 0.1 ng/mL, P = 0.02). Furthermore, BMD of BA
      children with jaundice was significantly lower than that of BA children without
      jaundice (P = 0.0005). BMD of BA patients was inversely correlated with serum
      levels of OPG (r = -0.452, P < 0.001). CONCLUSION: Elevated serum OPG levels are
      associated with reduced BMD and the outcome of BA. The increase of serum OPG in
      BA patients with severe disease could reflect a compensatory response to bone
      loss.

PMID- 19184057
TI  - Different polyunsaturated fatty acid profiles in patients with biliary atresia
      after successful Kasai operation and liver transplantation.
AB  - BACKGROUND: Although Kasai operation eliminates jaundice in patients with biliary
      atresia, inflammation at Glisson's area persists and fibrosis advances slowly to
      liver cirrhosis. Profiles of polyunsaturated fatty acids, on which metabolic
      products have an immunoregulative effect, were investigated in this study.
      METHODS: Blood samples were obtained from patients including 21 jaundice-free
      patients with biliary atresia after Kasai operation (native liver group) and 18
      patients in whom Kasai operation failed and liver transplantation was performed
      (transplantation group). All of these patients are without any complications for
      more than 6 months. Blood samples from 18 patients with inguinal hernia were
      assigned as normal controls (control group). Profiles of fatty acids in whole
      serum lipids were measured using gas chromatography. The n-3/n-6 ratio of
      polyunsaturated fatty acids was compared among the three groups. RESULTS: The n
      3/n-6 ratio was 0.114 in the native liver group, which was significantly lower
      than 0.145 in the transplantation group (P = 0.009) and 0.158 in the control
      group (P = 0.004). There was no significant difference between the
      transplantation and control groups (P = 0.83). RESULTS: The n-3/n-6 ratio was
      abnormal after Kasai operation despite normal liver function. This seems to be
      one factor of persisting inflammation in Glisson's area.

PMID- 19184058
TI  - Antenatally detected double prostatic utricle found in a neonate with ambiguous
      genitalia.
AB  - Although enlarged prostatic utricle is usually seen in patients with hypospadias
      and disorders of sex development, double utricle has not been reported without
      unilateral renal dysplasia and Wolffian duct anomaly. We present an unusual case
      of antenatally detected large pelvic cyst, which turned out to be one of double
      prostatic utricles in a neonate with ambiguous genitalia. The possibility of
      enlarged utricle should be considered in the differential diagnosis of
      antenatally detected pelvic cysts in neonates with ambiguous genitalia.

PMID- 19184059
TI  - A meta-analysis of randomized controlled trials comparing chemotherapy plus
      bevacizumab with chemotherapy alone in metastatic colorectal cancer.
AB  - PURPOSE: Bevacizumab has demonstrated survival benefit in metastatic colorectal
      cancer (mCRC) patients when combined with chemotherapy. Several randomized
      clinical studies have evaluated bevacizumab in combination with chemotherapy.
      Meta-analysis was performed to better assess the efficacy and safety of
      bevacizumab with chemotherapy for mCRC. MATERIALS AND METHODS: Five clinical
      trials randomizing a total of 3,103 mCRC patients to chemotherapy alone or to the
      combined treatment of chemotherapy plus bevacizumab were identified. The efficacy
      data included progression-free survival (PFS), overall survival (OS), and overall
      response rate (ORR), and the safety data contained the 60-day all-cause mortality
      rate, adverse events (AEs), and specific toxicity such as hypertension,
      thrombosis, bleeding, proteinuria, gastrointestinal perforation, diarrhea, and
      leucopenia. RESULT: There was a significant PFS benefit (P = 0.00; hazards ratio
      [HR] = 0.66) and OS benefit (P = 0.00; HR = 0.77) in favor of the combined
      treatment. The ORR was significantly higher on the bevacizumab-containing arm (P
      = 0.021; relative risk [RR] = 1.5), while CR was comparable between the two arms
      (P = 0.09). A higher incidence of grade 3/4 AEs, grade 3/4 hypertension, grade
      3/4 thromboembolic/thrombotic events, grade 3/4 bleeding, and gastrointestinal
      perforation was associated with the bevacizumab group. The two treatment groups
      were similar in terms of grade 3/4 proteinuria, grade 3/4 leukopenia, grade 3/4
      diarrhea, and the 60-day all-cause mortality rate. CONCLUSION: The addition of
      bevacizumab to chemotherapy confers a clinically meaningful and statistically
      significant improvement in OS, PFS, and ORR. Its side effects are predictable and
      manageable and do not compound the incidence or severity of toxicities from
      chemotherapy.

PMID- 19184060
TI  - Expression of tight and adherens junction proteins in ulcerative colitis
      associated colorectal carcinoma: upregulation of claudin-1, claudin-3, claudin-4,
      and beta-catenin.
AB  - BACKGROUND: Tight junction (TJ) proteins play a critical role in cellular
      adhesion, glandular differentiation, and cellular proliferation. The function of
      these proteins is compromised in a number of intestinal diseases, including
      ulcerative colitis that has an increased incidence for colorectal carcinoma
      (CAC). The aim of this study was to determine the expression of TJ proteins,
      claudin-1-4, occludin, ZO-1, and the adherens junction (AJ) protein beta-catenin
      in CAC. METHODS: Sixteen colectomy specimens with CAC, adjoining intraepithelial
      neoplasia, and normal mucosa were studied by immunofluorescence. A
      semiquantitative evaluation of all investigated proteins was performed by scoring
      the staining intensity, and the TJ and AJ protein expression in neoplastic cells
      was compared to normal and intraepithelial neoplastic colonic mucosa. RESULTS:
      Using an intensity scoring system, mucosa of crypts and surfaces of CAC exhibited
      significantly elevated expression levels of claudin-1, claudin-3, claudin-4, and
      beta-catenin compared to intraepithelial neoplasia and normal mucosa (p<0.05).
      These data were confirmed by a comparative score. The expression of claudin-2,
      occludin, and ZO-1 showed no differences between the groups. CONCLUSION: TJ
      proteins claudin-1, claudin-3, claudin-4, and the AJ protein beta-catenin are
      overexpressed in CAC. This suggests that these proteins may become potential
      markers and targets in CAC.

PMID- 19184061
TI  - Liver metastases after colonic carcinoma--palliative chemotherapy plus curcumin.

PMID- 19184062
TI  - Syndrome of inappropriate antidiuresis (SIAD) in a patient with rectal carcinoma
      undergoing preoperative radiation.

PMID- 19184063
TI  - Colonic conduit for esophageal bypass in Celphos-induced tracheoesophageal
      fistula: our experience of two cases.

PMID- 19184064
TI  - Effects of cyclooxygenase inhibition on anastomotic healing following large bowel
      resection in a rabbit model--a randomized, blinded, placebo-controlled trial.
AB  - PURPOSE: We performed an experimental study in a rabbit model to investigate the
      effects of a selective Cox-2 inhibitor (Valdecoxib) on anastomotic healing
      following large bowel resection after 1 week. MATERIALS AND METHODS: Eighty New
      Zealand white rabbits were randomized into four groups and underwent a colon
      resection with end-to-end anastomosis. Group 1 (n = 20) was treated with
      Valdecoxib, group 2 with Metamizole (Novalgin), group 3 with Resveratrol
      (specific Cox-1 inhibitor), or a placebo vehicle with similar volume (group 4).
      Anastomotic healing was tested at the seventh postoperative day by measurement of
      the bursting pressure in vitro. Immunohistochemical staining of the anastomotic
      site was performed with polyclonal antibodies (CD31). RESULTS: There were no
      significant differences in anastomotic dehiscence, bursting pressure, or vessel
      density between the treatment and control groups. CONCLUSION: The application of
      Valdecoxib does not influence anastomotic healing or new vessel formation in the
      anastomotic region following large bowel resection.

PMID- 19184065
TI  - Small intestinal submucosa for reinforcement of colonic anastomosis.
AB  - BACKGROUND: Different materials have been evaluated for anastomotic reinforcement
      to prevent gastrointestinal anastomotic leakage. In this experimental study,
      small intestinal submucosa (SIS) was tested as a sealing for stapled colonic
      anastomosis in a porcine model. The aims of this study were to determine the
      macroscopic and microscopic outcomes and to evaluate the safety and feasibility
      of applying SIS for anastomotic sealing. MATERIALS AND METHODS: Circular stapled
      anastomoses were performed in 18 pigs. Standard anastomosis in the control group
      (n = 8) was compared to an SIS-sealed anastomosis in the study group (n = 10).
      After 30 days, anastomotic segments were examined for macroscopic and microscopic
      regeneration and their resistance to mechanical stress. Furthermore, animal
      survival and clinical course were evaluated. RESULTS: None of the animals
      developed anastomotic leakage, intraabdominal abscess, or peritonitis. Shrinkage
      of SIS was evident in nine of ten animals. Encapsulation and displacement of the
      SIS patches were seen in two animals. Quantity of anastomotic granulation tissue
      and rate of complete mucosal coverage of anastomotic line were increased in SIS
      sealed anastomoses without reaching significance. Moreover, no significant
      differences were found in the rate of survival of the animals, anastomotic
      stricture formation, intraabdominal adhesions, anastomotic bursting pressure, and
      microscopic healing parameters of the anastomosis between stapled colonic
      standard anastomosis and anastomosis protected by SIS. CONCLUSION: The results of
      this study indicate a safe use of SIS for anastomotic reinforcement in a porcine
      model. Adverse effects like strictures, increased adhesions, and anastomotic
      abscesses were absent. Promoting effects on colonic wound healing by SIS were
      microscopically evident. The results argue for a careful clinical evaluation in
      humans.

PMID- 19184066
TI  - [Wegener's granulomatosis and microscopic polyangiitis].
AB  - Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are primary
      systemic small vessel vasculitides, associated with a positive C/PR3-ANCA in WG
      and P/MPO-ANCA in MPA. The most prominently involved organs are the upper (only
      in WG) and lower respiratory tract and the kidneys. The diagnostic work-up is an
      interdisciplinary approach assessing disease stage and extent. Treatment is
      adapted to disease stage and extent and relies on a combination of a cytotoxic
      plus a tapering regimen of corticosteroids. Induction of remission in "early
      systemic" disease can be achieved with low-dose methotrexate. In severe
      generalized vasculitis cyclophosphamide (CYC) is the mainstay of therapy, in
      rapidly progressive glomerulonephritis in combination with plasmapheresis. After
      3-6 months of induction CYC is switched to a maintenance treatment with
      azathioprine. Alternatives are leflunomide, mycophenolate or methotrexate
      (creatinine < 150 micromol/l). Age > or = 50 at diagnosis, renal dysfunction and
      pulmonary involvement are associated with higher mortality rates. The relapse
      rate is approximately 50% within 5 years, being higher in WG than MPA.

PMID- 19184067
TI  - Sarcoplasmic hexagonally cross-linked tubular arrays immunostain for caveolin-3:
      an excess caveolinopathy?

PMID- 19184069
TI  - Ventricular tachycardia during arthroscopic shoulder surgery: a report of two
      cases.
AB  - We routinely have performed arthroscopic shoulder surgery under general
      anesthesia in the beach chair position using epinephrine (0.33 mg/L) saline
      irrigation. At a 2-week interval, two patients, a 19-year-old man scheduled to
      undergo an arthroscopic Bankart repair for left traumatic anterior instability
      and a 49-year-old woman scheduled for an arthroscopic rotator cuff repair for a
      left rotator cuff tear, were resuscitated by chest compression and defibrillation
      due to a sudden developed cardiogenic shock following ventricular tachycardia at
      the time of arthroscopic shoulder surgery. They were transferred to the intensive
      care unit because their emergent echocardiogram showed significantly decreased
      cardiac functions. They were fully recovered and then discharged. Epinephrine was
      considered to be the cause of ventricular tachycardia because the two patients
      showed no anaphylactic reaction to drugs or symptoms of air embolism related to
      the beach chair position. In addition, according to our observation of
      epinephrine flow patterns, it was more likely that highly concentrated
      epinephrine was rapidly infused into the body. This complication is very rare.
      However, thorough understanding of the side effects and their development of
      epinephrine during arthroscopic shoulder surgery should neither be overemphasized
      nor disregarded.

PMID- 19184070
TI  - Usefulness of a navigation system in surgery for scoliosis: segmental pedicle
      screw fixation in the treatment.
AB  - STUDY DESIGN: Postoperative outcomes of segmental pedicle screw fixation were
      evaluated in posterior scoliosis surgery with the use of navigation system.
      OBJECTIVES: We report the usefulness of a navigation system and a segmental
      pedicle screw fixation in surgery for scoliosis. SUMMARY OF BACKGROUND DATA: Few
      reports on a segmental pedicle screw fixation method for scoliosis surgery using
      a navigation system have been published. This is the report on the usefulness of
      a navigation system in segmental pedicle screw fixation. METHODS: We targeted 16
      cases in which segmental pedicle screw fixation had been performed using a
      navigation system at our hospital. We inserted 264 pedicle screws in total, and
      we did not perform registration for each corpus vertebrate in order to shorten
      the duration of the surgery. We reviewed screw deviation among the items for
      review using Neo classification with postoperative CT images (1.25 mm). For screw
      deviation in this case, grade 2 or higher in the Neo classification system was
      designated as total deviation. Furthermore, we evaluated the registration period
      per corpus vertebrae, the complications, duration of surgery, blood loss, Cobb
      angle, and the correction rate. RESULTS: In terms of screw deviation, 11 (4.2%)
      of the 264 inserted screws were classified as total deviation. However, there
      were no neurovascular complications during or after surgery in any cases, and all
      cases maintained strong internal fixation. In the relationship between the use or
      nonuse of registration and the deviation, four screws (3.2%) in the corpus
      vertebrae for which registration was performed and seven screws (5.0%) in the
      adjacent corpus vertebrae for which registration was not performed had deviated.
      The duration of registration per corpus vertebrate averaged 4 min and 24 s (58
      791 s), but registration also requires a learning curve, so the duration of
      registration per corpus vertebrae averaged 1 min and 14 s in more recent cases,
      thus marking a significant shortening. CONCLUSION: Segmental pedicle screw
      fixation are excellent in regard to their fixing and correction force and have
      been clinically applied even in surgery for scoliosis, but the potential risk of
      neurovascular complications is unavoidable. The adoption of a navigation system
      in surgery for scoliosis is useful to increase the safety and certainty of the
      insertion of pedicle screws.

PMID- 19184071
TI  - The expression of differentiation markers in aquaporin-3 deficient epidermis.
AB  - Aquaporin-3 (AQP3) is a water/glycerol transporting protein expressed strongly at
      the plasma membrane of keratinocytes. There is evidence for involvement of AQP3
      facilitated water and glycerol transport in keratinocyte migration and
      proliferation, respectively. Here, we investigated the involvement of AQP3 in
      keratinocyte differentiation. Studies were done using AQP3 knockout mice, primary
      cultures of mouse keratinocytes (AQP3 knockout), neonatal human keratinocytes
      (AQP3 knockdown), and human skin. Cells were cultured with high Ca(2+) or
      1alpha,25-dihydroxyvitamin D(3) (VD(3)) to induce differentiation. The expression
      of differentiation marker proteins and differentiating responses were comparable
      in control and AQP3-knockout or knockdown keratinocytes. Topical application of
      all-trans retinoic acid (RA), a known regulator of keratinocyte differentiation
      and proliferation, induced comparable expression of differentiation marker
      proteins in wildtype and AQP3 null epidermis, though with impaired RA-induced
      proliferation in AQP3 null mice. Immunostaining of human and mouse epidermis
      showed greater AQP3 expression in cells undergoing proliferation than
      differentiation. Our results showed little influence of AQP3 on keratinocyte
      differentiation, and provide further support for the proposed involvement of AQP3
      facilitated cell proliferation.

PMID- 19184068
TI  - Mechanisms of tau-induced neurodegeneration.
AB  - Alzheimer disease (AD) and related tauopathies are histopathologically
      characterized by a specific type of slow and progressive neurodegeneration, which
      involves the abnormal hyperphosphorylation of the microtubule associated protein
      (MAP) tau. This hallmark, called neurofibrillary degeneration, is seen as
      neurofibrillary tangles, neuropil threads, and dystrophic neurites and is
      apparently required for the clinical expression of AD, and in related tauopathies
      it leads to dementia in the absence of amyloid plaques. While normal tau promotes
      assembly and stabilizes microtubules, the non-fibrillized, abnormally
      hyperphosphorylated tau sequesters normal tau, MAP1 and MAP2, and disrupts
      microtubules. The abnormal hyperphosphorylation of tau, which can be generated by
      catalysis of several different combinations of protein kinases, also promotes its
      misfolding, decrease in turnover, and self-assembly into tangles of paired
      helical and or straight filaments. Some of the abnormally hyperphosphorylated tau
      ends up both amino and C-terminally truncated. Disruption of microtubules by the
      non-fibrillized abnormally hyperphosphorylated tau as well as its aggregation as
      neurofibrillary tangles probably impair axoplasmic flow and lead to slow
      progressive retrograde degeneration and loss of connectivity of the affected
      neurons. Among the phosphatases, which regulate the phosphorylation of tau,
      protein phosphatase-2A (PP2A), the activity of which is down-regulated in AD
      brain, is by far the major enzyme. The two inhibitors of PP-2A, I (1) (PP2A) and
      I (2) (PP2A) , which are overexpressed in AD, might be responsible for the
      decreased phosphatase activity. AD is multifactorial and heterogeneous and
      involves more than one etiopathogenic mechanism.

PMID- 19184072
TI  - Ultraviolet A irradiation of the eye induces immunomodulation of skin and
      intestine in mice via hypothalomo-pituitary-adrenal pathways.
AB  - Irradiation by ultraviolet A (UVA) initiates the suppression of skin contact
      hypersensitivity. However, the change in the whole body immunity by UVA
      irradiation of the eye is still unknown. The mice used in this study were
      separated into four groups namely: a control, UVA irradiation of the eye, UVA
      irradiation of the ear, UVA irradiation of the eye + a glucocorticoid receptor
      antagonist (RU-486) administrated, UVA irradiation of the eye with an
      adrenalectomy and non-irradiation + cortisol administrated groups. The eye or ear
      was locally exposed to UVA after covering the remaining body surface with
      aluminum foil at a dose of 110 kJ/m(2) using a FL20SBLB-A lamp. Plasma
      adrenocorticotropic hormone, cortisol, and interleukin-10 (IL-10) content
      increased by UVA irradiation of the eye. In addition, UVA irradiation of the eye
      induced down-regulation of the epidermal Langerhans cells in the ear and the up
      regulation of the mucosal immunoglobulin A (IgA) in the intestine. However, the
      changes in the epidermal Langerhans cells and mucosal IgA of UVA irradiation of
      the eye are not induced either by the RU-486 treatment or an adrenalectomy. These
      results clearly indicate that the signal evoked by UVA irradiation of the eye,
      through the hypothalamo-pituitary-adrenal pathway, up-regulated the production of
      glucocorticosterone. This hormone controls immunity, and the possibility that it
      performed a living body defense for UVA exposure was thus suggested.

PMID- 19184073
TI  - Peritoneal tuberculosis with elevated serum Ca-125 level mimicking advanced stage
      ovarian cancer: a case report.
AB  - BACKGROUND: Tuberculosis is still a common problem in immigrant population with
      peritoneal tuberculosis as the most common presentation of extrapulmonary
      disease. CASE: A 36-year-old woman presented with abdominal distention, night
      sweats and weight loss. Physical examination and radiologic studies revealed
      ascites, omental caking and bilateral enlarged ovaries with an elevated serum Ca
      125 of 353 U/mL. Acid-fast stain and culture were negative for Mycobacterium
      tuberculosis. Diagnostic laparoscopy and biopsy revealed multiple granulomas with
      epithelioid cells and caseification necrosis confirming tuberculosis. Treatment
      with anti-tuberculin drugs resulted in resolution of symptoms with a reduction in
      Ca-125 to normal. CONCLUSION: Laparoscopic biopsy with frozen section evaluation
      would spare patients with peritoneal tuberculosis from unnecessary extensive
      surgery. Serum Ca-125 level may be useful in monitoring treatment response.

PMID- 19184074
TI  - Three isolated, large retroperitoneal leiomyomas.
AB  - Leiomyomas are very rare as retroperitoneal neoplasms. The pathogenesis of
      retroperitoneal leiomyomas remains obscure. A 42-year-old multiparous woman
      presented with a large abdominopelvic mass. At surgery, the uterus was displaced
      laterally to the right and the right kidney was displaced medially by three
      isolated large retroperitoneal masses. A total abdominal hysterectomy and
      complete excision of the retroperitoneal masses was performed. The
      histopathologic findings of the resected three tumors revealed leiomyomas without
      evidence of malignancy and the remaining surgical specimens were normal. This is
      the first case of three isolated large retroperitoneal leiomyomas without a
      uterine leiomyoma. The distribution of retroperitoneal leiomyomas in our case
      suggests that these may be of primary multifocal origin, rather than metastatic
      or parasitic.

PMID- 19184075
TI  - Experience with laparoscopic-assisted vaginal hysterectomy for the enlarged
      uterus.
AB  - OBJECTIVE: The aim of this study is to evaluate the effect of uterine weight on
      the perioperative and postoperative outcomes of laparoscopically assisted vaginal
      hysterectomy (LAVH) for benign gynecological conditions. METHODS: In a
      retrospective observational study, 367 patients underwent LAVH (type I
      laparoscopic hysterectomy) for benign disorders at the Department of Gynecology
      at the Istanbul Bakirkoy Women and Children Hospital. Patients were divided into
      two groups with uterine weight <500 g and uterine weight > or =500 g. Outcome
      measures for both groups were studied comparatively in terms of length of
      operative time, pain score, amount of blood loss, requirement of blood
      transfusion, and length of hospital stay. RESULTS: There were no differences in
      patients' mean age, parity, gravidity, rate of postmenopausal state, previous
      pelvic surgery, and body mass index. The most common indications for surgery were
      myoma and abnormal uterine bleeding. The duration of operation, estimated blood
      loss and requirement of blood transfusion were significantly less for <500 g
      group than for > or =500 g group. Three women in the <500 g group sustained a
      blood loss in excess of 500 ml. By comparison, 18 women in the > or =500 g group
      sustained a blood loss in excess of 500 ml (P = 0.000). Total complication rate
      was 8.7%. Postoperative ileus and febrile morbidity were the most common
      complications. No significant difference was noted in overall complications
      between groups (P = 0.13). During the vaginal part of the procedure bladder
      injury occurred in one patient who had uterine weight > or =500 g. CONCLUSION:
      LAVH is a safe and efficient way to manage benign uterine disease and despite the
      increased operating time and blood loss, LAVH can be safely performed for
      enlarged uterus.

PMID- 19184076
TI  - Mucosal changes in chronic hypertrophic rhinitis after surgical turbinate
      reduction.
AB  - Chronic nasal obstruction owed to chronic hypertrophic rhinitis is one of the
      most common problems encountered in rhinology. Various forms of conservative
      therapy have been used, but these are often ineffective and surgical reduction
      techniques have been successfully applied. However, the issue of postoperative
      histological changes in the nasal mucosa has not been adequately addressed. The
      aim of the present study was to comparatively evaluate the effect of the methods
      of submucosal monopolar diathermy, radiofrequency coblation and ultrasounds on
      the nasal mucosa. Sixty patients with chronic hypertrophic rhinitis of
      nonallergic etiology underwent different surgical methods of turbinate reduction,
      divided into two groups: (1) 30 patients underwent tissue volume reduction of the
      inferior nasal turbinates using ultrasound procedure on the left side and
      monopolar diathermy on the right; (2) 30 patients underwent radiofrequency
      coblation technique on the left side and ultrasound reduction on the right. We
      studied 20 preoperative specimens of the inferior turbinate mucosa taken randomly
      from both groups of patients, 5 from each side of each group. Normal nasal
      mucosal specimens taken from ten healthy persons were used as controls. Specimens
      of the inferior turbinate were taken after 1, 3, and 6 months after surgery, from
      the same patients. All specimens were examined by electron microscopy.
      Preoperative observation revealed degeneration of epithelial cells, loss of
      cilia, disruption of intercellular connections, edema, nasal mucus overproduction
      and inflammatory infiltration in chorium. Postoperative observations revealed
      decrease of intercellular edema, reduction of mucus, overproduction of collagen
      and degeneration of the epithelium to flattened stratified. Only specimens after
      use of ultrasounds showed islands with normally organized epithelium of columnar
      ciliated cells. It may be concluded that epithelial changes owed to chronic
      hypertrophic rhinitis do not significantly improve postoperatively after
      turbinate tissue volume reduction. Only in several cases operated with
      ultrasounds, regeneration of epithelium occurs, resulting to anatomical and
      functional restoration of the nasal physiology.

PMID- 19184077
TI  - Influence of head positioning on the forces occurring during microlaryngoscopy.
AB  - Considerable forces are exerted on oropharyngeal tissues during
      microlaryngoscopic procedures. Although it is generally accepted that positioning
      of the patient's head influences the quantity of these forces and the easiness of
      the exposure of the anterior glottis, there is a lack of systematic studies on
      this topic. The aim of our study was to measure the forces occurring during
      microlaryngoscopy in different positions. This should result in a recommendation
      for a "low-pressure" position which minimises the risk of postoperative
      complications due to tissue trauma. Thirty consecutive patients planned for
      microlaryngoscopy underwent study procedures. During general anaesthesia,
      measurements were taken using a tension spring balance in neutral position,
      during extension of the cervical spine, as well as under moderate and maximum
      flexion. Elevation of the patient's head thus flexing the cervical spine reduced
      the occurring forces significantly. Maximum elevation allowed a full exposure of
      the anterior commissure in all cases, whereas exposure of the anterior commissure
      was not possible even with maximum external counterpressure in almost 40% of
      cases with maximum extended cervical spine. The largest differences were observed
      between extension, neutral and flexion position, whereas the differences between
      moderate and maximum flexion were not significant. Elevation of the patient's
      head with consecutive flexion of the cervical spine allows for better exposure in
      microlaryngoscopy and reduces significantly the pressure exerted on the
      oropharyngeal tissues thus minimising the risk of tissue injury. A slight
      modification of standard instruments can be necessary when using this "low
      pressure" position.

PMID- 19184078
TI  - From the expert's office: localized neural lesions following tonsillectomy.
AB  - Due to various reasons, localized neural lesions following tonsillectomy are
      presumably an under-reported complication in the literature. This study was
      undertaken to compile our experiences including a literature review to
      disseminate useful insights in the etiology and prognosis of this rare entity. A
      retrospective chart review of expert reports written by at least one of the
      authors for malpractice claims in relation to tonsillectomy was undertaken.
      Additionally, a retrospective analysis of 648 patient documents that had
      undergone tonsillectomy in 2001 at our institution and a comprehensive literature
      review were performed. The research was restricted to the item "localized neural
      lesion". Seven cases from the expert's offices, one of our patients who had
      undergone tonsillectomy at our institution and 122 cases from the literature
      matched our search criteria. Including our own cases, the glossopharyngeal nerve
      was affected in 82 patients. Other lesions encompassed injury of the hypoglossal
      nerve as solitary (15) or combined (5) lesion, recurrent nerve paralysis with (2)
      or without additional nerve lesions (7), facial nerve paralysis (10) in
      combination with other nerve lesions (1), and a lingual nerve deficiency as
      solitary (4) or combined lesion (9). A single report existed for lesion of the
      phrenic nerve. There were five reported cases with blindness and nine cases with
      Horner's syndrome. Albeit rare, localized neural lesions may occur as a
      troublesome complication following tonsillectomy and/or means to achieve
      hemostasis. Some of these cases may not result from the dissection itself but
      injection procedures. Surgical dissection should include careful mouth gag
      insertion and meticulous dissection to minimize the risk of localized neural
      complications. A long-term follow-up is recommended for patients with dysgeusia
      related to glossopharyngeal nerve injury and patients with recurrent nerve
      dysfunction. Other lesions are much less likely to resolve in the long-term.
      Localized neural lesions should adequately be included in the informed consent
      for tonsillectomy as well as for surgical treatment of post-tonsillectomy
      hemorrhage.

PMID- 19184079
TI  - Time-dependent expression of skeletal muscle troponin I mRNA in the contused
      skeletal muscle of rats: a possible marker for wound age estimation.
AB  - To estimate the age of skeletal muscle contusion, the expression of troponin I
      mRNA in contused skeletal muscle of rats was detected using real-time polymerase
      chain reaction (PCR). A total of 51 Sprague-Dawley male rats were divided into
      control and contusion groups, and another nine rats received contusion injury
      after death. At 0.5, 1, 6, 12, 18, 24, 30, and 36 h after contusion, the rats
      were killed with a lethal dose of pentobarbital. Total RNA was isolated from
      muscle specimens using the SV Total RNA Isolation System and reverse transcribed
      into first-strand cDNA. Sequence-specific primers were then used to conduct real
      time PCR to analyze the expression levels of sTnI mRNA. At 0.5, 1, and 6 h after
      contusion, the expression levels of sTnI mRNA decreased to 78.17% (P < 0.05),
      41.58% (P < 0.05), and 32.13% of that in the control group, respectively.
      However, there were no significant changes in the expression levels of sTnI mRNA
      from 6 to 36 h (P > 0.05) after contusion when normalized to RpL32 expression.
      The expression levels of sTnI mRNA in the normal and contused skeletal muscle of
      postmortem rats were about 70% of that in the control group (P < 0.05), and no
      significant changes in the expression levels of sTnI mRNA in the postmortem
      contusion group were noted among different time points after injury. This result
      suggests that determination of sTnI mRNA levels by real-time PCR is useful for
      the estimation of wound age.

PMID- 19184080
TI  - Tear fluid concentration of mmp-8 is elevated in non-allergic eosinophilic
      conjunctivitis and correlates with conjunctival inflammatory cell infiltration.
AB  - BACKGROUND: To investigate tear fluid concentration of matrix metalloproteinase 8
      (MMP-8) and its relation to conjunctival inflammatory cell infiltration in
      persistent non-allergic eosinophilic conjunctivitis (NAEC). METHODS: Two groups
      were included: 26 consecutive adult patients with NAEC (conjunctival eosinophils
      at least 1+ [1-10 eosinophils/slide], skin prick test [SPT] to common allergens
      negative), and 26 asymptomatic adult persons (no conjunctival eosinophils, SPT
      negative). MMP-8 tear fluid concentrations were determined by immunofluorometric
      assay, and conjunctival brush cytology samples from NAEC patients were used for
      MMP-8 immunocytochemistry. Gelatin zymography was used to illustrate proteolytic
      activity within the tear fluid samples. RESULTS: The mean MMP-8 concentration was
      significantly higher among NAEC patients (214.3 +/- 327.7 microg/l) than among
      healthy persons (50.4 +/- 62.3 microg/l, P < 0.0001). In the NAEC patients, tear
      fluid MMP-8 correlated with the numbers of conjunctival neutrophils (r = 0.66, P
      = 0.0002) as well as with goblet cells and columnar epithelial cells (r = 0.54
      for both, P = 0.045), but not with the lymphocyte numbers (r = -0.36, P =
      0.0741). By immunocytology, MMP-8 protein could also be detected in vivo in the
      inflammatory cell population within the conjunctiva. Zymography revealed that
      proteolysis was significantly higher in the NAEC group, and activated enzymes
      were practically found only in the NAEC group. CONCLUSIONS: The results showed
      that NAEC is an inflammatory condition characterized by increased tear fluid MMP
      8 levels, probably derived from both inflammatory and structural conjunctival
      cells. The increased proteolytic activity in NAEC patients may indicate risk of
      conjunctival structural changes (remodeling).

PMID- 19184081
TI  - Efficacy and safety of latanoprost in eyes with uveitic glaucoma.
AB  - BACKGROUND: To compare the efficacy and safety of latanoprost against a fixed
      combination of dorzolamide and timolol in eyes with elevated intraocular pressure
      (IOP) or glaucoma and anterior or intermediate uveitis. METHODS: Fifty-eight
      patients with anterior or intermediate uveitis and elevated IOP or glaucoma
      presented or followed up in the Ocular Inflammation and Immunology Service of
      General Hospital of Athens were randomly assigned to receive treatment either
      with latanoprost (30) or with dorzolamide/timolol (28). The main outcome measures
      were inflammatory relapses and IOP response to treatment. RESULTS: Ten patients
      (34%) in the latanoprost group and sixteen patients (57%) in the
      dorzolamide/timolol group experienced relapses of anterior uveitis (p = 0.93).
      There was no statistical difference between the two groups in respect of
      inflammatory relapses (p = 0.21). Twenty-one patients were followed up before
      starting latanoprost. The number of recurrences of anterior uveitis per patient
      per year before treatment with latanoprost was 0.82 +/- 1.2. The rate of relapses
      per patient per year after starting latanoprost was 0.39 +/-0.7 for these
      patients (p = 0.038). After 1 year of treatment, intraocular pressure was dropped
      from 27.8 +/- 8.4 mmHg to 18.6 +/- 5.3 mmHg (p < 0.001) in the latanoprost group
      and from 28.2 +/-8.1 mmHg to 22.6 +/-10.1 mmHg (p < 0.001) in the
      dorzolamide/timolol group. Four patients during treatment with latanoprost and
      five patients during treatment with dorzolamide/timolol developed macular edema.
      CONCLUSION: Latanoprost is safe and equally effective to a fixed combination of
      dorzolamide and timolol in the treatment of uveitic glaucoma.

PMID- 19184083
TI  - The rotor pedaling system improves anaerobic but not aerobic cycling performance
      in professional cyclists.
AB  - The aims of this study were to evaluate the effects of both noncircular (ROT) and
      conventional (CON) chainring systems on aerobic and anaerobic cycling
      performances of professional cyclists, while analyzing the influence of varying
      the crank angle of maximum crank arm length of ROT. Fifteen professional road
      cyclists performed both incremental and sub-maximal aerobic tests and the Wingate
      anaerobic test in the laboratory. There were no statistical differences between
      CON and ROT in the aerobic tests, even when the best ROT position (ROT+) was
      selected. However, in the anaerobic test, maximal (4.2-9.1%) and mean (0.7-4.7%)
      power outputs were higher in ROT (P < 0.05). These differences were greater when
      the ROT+ was selected (11.2 and 7.0%, respectively). Our findings suggest that
      ROT is able to improve anaerobic but not aerobic cycling performance in
      professional cyclists. Nevertheless, it must be adapted to each cyclist to ensure
      these improvements.

PMID- 19184082
TI  - Macular autofluorescence in eyes with cystoid macula edema, detected with 488 nm
      excitation but not with 580 nm-excitation.
AB  - BACKGROUND: Fundus autofluorescence (AF) derives from lipofuscin in the retinal
      pigment epithelium (RPE). Because lipofuscin is a by-product of phagocytosis of
      photoreceptors by RPE, AF imaging is expected to describe some functional aspect
      of the retina. In this study we report distribution of AF in patients showing
      macular edema. METHODS: Three eyes with diabetic macular edema (DME) and 11 with
      retinal vein occlusion (RVO), associated with macular edema (ME) were examined.
      ME was determined by standard fundus examination, fluorescein angiography (FA)
      and optical coherence tomography (OCT). AF was recorded using a Heidelberg
      confocal scanning laser ophthalmoscope (cSLO) with 488 nm laser exciter (488 nm
      AF), and a conventional Topcon fundus camera with halogen lamp exciter and 580 nm
      band-pass filter (580 nm-AF). Color fundus picture, FA image and these two AF
      images were analyzed by superimposing all images. RESULTS: All subjects presented
      cystoid macular edema (CME) with petaloid pattern hyperfluorescence in FA. In 488
      nm-AF, all eyes (100%) showed macular autofluorescence of a similar shape to that
      of the CME in FA. In contrast, in 580 nm-AF only one eye (7%) presented this
      corresponding petaloid-shaped autofluorescence. In all cases, peripheral retinal
      edemas did not show autofluorescence corresponding to the leakage in FA.
      CONCLUSIONS: In eyes with CME, analogous hyperautofluorescence to the CME was
      always observed in 488 nm-AF, while it was rarely observed in 580 nm-AF.
      Moreover, this CME hyperautofluorescence was only seen in the macular area. We
      hypothesize that autofluorescence from CME may be considered as a "pseudo" or
      "relative" autofluorescence, due to macular stretching following CME that may
      result in lateral displacement of macular pigments (MPs) and subsequent reduction
      of MPs density, as MPs block 488 nm-AF more intensely than 580 nm-AF. Although
      this phenomenon may not directly indicate change of RPE function, it may be used
      as a method to assess or track CME non-invasively.

PMID- 19184084
TI  - The effect of arm abduction angle and contraction intensity on perceived
      exertion.
AB  - The objective of the present investigation was to examine the effects of
      voluntary contraction intensity and arm elevation angle on ratings of perceived
      exertion in healthy young adults. Twelve healthy young adults participated in six
      separate experimental sessions, during which maximal and sub-maximal arm
      abduction contractions were performed at one of the following randomly assigned
      arm angles: 15 degrees , 30 degrees , 45 degrees , 60 degrees , 75 degrees , and
      90 degrees arm angles (degrees). The sub-maximal arm abduction contractions (10
      s) were performed to target intensities ranging from 10 to 90% of the maximal
      voluntary contraction (MVC), in randomly ordered 10% increments. Perceived
      exertion was sampled with a modified Borg category-ratio scale immediately,
      following each sub-maximal contraction. Voluntary arm abduction torque was
      significantly (p < 0.05) lower at 45 degrees , 60 degrees , 75 degrees and 90
      degrees , as compared to 15 degrees . The ratings of perceived exertion increased
      significantly (p < 0.05) across the range of contraction intensities, with no
      significant differences between arm angles. The perceived exertion response, as a
      function of contraction intensity, was best described as linear across the 30
      degrees -90 degrees , while a power function described the response at 15 degrees
      . The major findings demonstrated that arm position plays a minimal role in
      mediating the growth in the perceived exertion response, as a function of
      contraction intensity.

PMID- 19184086
TI  - Reaction time to peripheral visual stimuli during exercise under normoxia and
      hyperoxia.
AB  - The purpose of this study was to test if increased oxygen availability affected
      simple reaction time (RT) to peripheral visual stimuli during exercise. Twelve
      male participants performed RT tasks at rest, during cycling with three different
      workloads (100, 150, and 200 W), and after exercise. We fractionated RT into
      Premotor time and Motor time. Under normoxia, Premotor time significantly
      increased during exercise at 200 W (mean +/- SD, 224.7 +/- 34.8 ms) relative to
      that at rest (213.3 +/- 34.1 ms) (P < 0.05). In contrast, we found no difference
      in Premotor time between at rest (214.0 +/- 27.0 ms) and at 200 W (213.0 +/- 21.6
      ms) under hyperoxia. Furthermore, Premotor time significantly decreased at 150 W
      (201.3 +/- 22.4 ms) relative to that at rest under hyperoxia (P < 0.05). These
      results suggest that increased oxygen availability during exercise has beneficial
      effects on perceptual performance.

PMID- 19184087
TI  - Cumulative effects of consecutive running sessions on hemolysis, inflammation and
      hepcidin activity.
AB  - The effect of two running sessions completed within a 12-h period on hemolysis,
      inflammation, and hepcidin activity in endurance athletes was investigated. Ten
      males completed two experimental trials in a randomized, counterbalanced order.
      The two trials included (a) a one-running-session trial (T1) including 10 x 1 km
      interval repeats (90% peak VO2 velocity), and (b) a two-running-session trial
      (T2), comprising a continuous 10-km run (70% peak VO2 velocity), and a 10 x 1 km
      interval run (90% peak VO2 velocity) completed 12 h later. Interleukin-6 (IL-6),
      free hemoglobin (Hb), haptoglobin (Hp), iron, ferritin, and hepcidin were
      assessed post-exercise. After the T1 and T2 interval runs, free Hb was
      significantly increased and Hp significantly decreased (p <or= 0.05), with a
      cumulative effect shown in T2 after the second run (p <or= 0.05). The IL-6, serum
      iron, ferritin, and hepcidin activity were increased after each running session
      (p <or= 0.05), with no cumulative effect in T2. In conclusion, a cumulative
      effect of two running sessions on hemolysis was shown, but no similar effect with
      inflammation and hepcidin activity was evident.

PMID- 19184088
TI  - A neurally plausible model of the dynamics of motion integration in smooth eye
      pursuit based on recursive Bayesian estimation.
AB  - In this study, we describe a model of motion integration in smooth eye pursuit
      based on a recursive Bayesian estimation process, which displays a dynamic
      behaviour qualitatively similar to the dynamics of the motion integration process
      observed experimentally, both psychophysically in humans and monkeys, and
      physiologically in monkeys. By formulating the model as an approximate version of
      a Kalman filter algorithm, we have been able to show that it can be put into a
      neurally plausible, distributed recurrent form which coarsely corresponds to the
      recurrent circuitry of visual cortical areas V1 and MT. The model thus provides
      further support for the notion that the motion integration process is based on a
      form of Bayesian estimation, as has been suggested by many psychophysical
      studies, and moreover suggests that the observed dynamic properties of this
      process are the result of the recursive nature of the motion estimation.

PMID- 19184089
TI  - Combining frequency and time domain approaches to systems with multiple spike
      train input and output.
AB  - A frequency domain approach and a time domain approach have been combined in an
      investigation of the behaviour of the primary and secondary endings of an
      isolated muscle spindle in response to the activity of two static fusimotor axons
      when the parent muscle is held at a fixed length and when it is subjected to
      random length changes. The frequency domain analysis has an associated error
      process which provides a measure of how well the input processes can be used to
      predict the output processes and is also used to specify how the interactions
      between the recorded processes contribute to this error. Without assuming
      stationarity of the input, the time domain approach uses a sequence of
      probability models of increasing complexity in which the number of input
      processes to the model is progressively increased. This feature of the time
      domain approach was used to identify a preferred direction of interaction between
      the processes underlying the generation of the activity of the primary and
      secondary endings. In the presence of fusimotor activity and dynamic length
      changes imposed on the muscle, it was shown that the activity of the primary and
      secondary endings carried different information about the effects of the inputs
      imposed on the muscle spindle. The results presented in this work emphasise that
      the analysis of the behaviour of complex systems benefits from a combination of
      frequency and time domain methods.

PMID- 19184090
TI  - Mesh fixation with fibrin glue (Tissucol/Tisseel) in hernia repair dependent on
      the mesh structure--is there an optimum fibrin-mesh combination?--investigations
      on a biomechanical model.
AB  - BACKGROUND: Because of its hemostatic and adhesive properties, fibrin glue has
      been used in many areas of surgical treatment in recent years. One example is
      hernia repair, where fibrin gluing has become increasingly established as an
      alternative method for mesh fixation. Clinically, fixation with fibrin glue shows
      a reduced postoperative complication rate compared to other fixation methods
      (staples, sutures), particularly with regard to pain. MATERIALS AND METHODS: Six
      different lightweight meshes were tested: TiMesh light, TiMesh extralight,
      Parietene light, Ultrapro, Optilene LP, and BARD Soft Mesh. Two millimeters
      Tissucol was used for fixation. Five meshes from each group were tested on
      muscular tissue with and without fibrin glue. The defined defect was 4.5 cm in
      diameter. The biomechanical measurements were taken in a standardized way using a
      materials testing machine. The minimum fixation strength required was 32 N,
      calculated from a corresponding model. RESULTS: The fixation strength
      measurements without fibrin glue gave a mean value for all 30 meshes of 2.98 N
      with a SD of 0.92 N. This was far below the 32 N required. With fibrin glue, the
      mean of all the measurements (30 meshes) was 61.86 +/- 23.0 N (min 34.9 N, max
      97.3 N). The lowest value was recorded for Ultrapro (34.9 +/- 12.5 N). All the
      other meshes had a significantly higher fixation strength when fixed with fibrin
      glue than Ultrapro (p = 0.001). The best results were found for Optilene LP, and
      this was significantly better than all the other meshes (97.3 +/- 8.9 N; p <
      0.001). CONCLUSION: Given the adequate stability and superior biocompatibility of
      lightweight large pore monofilament polypropylene meshes, heavyweight
      polypropylene meshes should no longer be used. It is possible to achieve adequate
      fixation of the meshes using fibrin glue. However, careful consideration should
      be given to the particular structure of the mesh in each case. Not every mesh is
      equally suitable for this purpose.

PMID- 19184091
TI  - Kidney amino acid transport.
AB  - Near complete reabsorption of filtered amino acids is a main specialized
      transport function of the kidney proximal tubule. This evolutionary conserved
      task is carried out by a subset of luminal and basolateral transporters that
      together form the transcellular amino acid transport machinery similar to that of
      small intestine. A number of other amino acid transporters expressed in the
      basolateral membrane of proximal kidney tubule cells subserve either specialized
      metabolic functions, such as the production of ammonium, or are part of the
      cellular housekeeping equipment. A new finding is that the luminal Na(+)
      dependent neutral amino acid transporters of the SLC6 family require an
      associated protein for their surface expression as shown for the Hartnup
      transporter B(0)AT1 (SLC6A19) and suggested for the L: -proline transporter SIT1
      (IMINO(B), SLC6A20) and for B(0)AT3 (XT2, SLC6A18). This accessory subunit called
      collectrin (TMEM27) is homologous to the transmembrane anchor region of the renin
      angiotensin system enzyme ACE2 that we have shown to function in small intestine
      as associated subunit of the luminal SLC6 transporters B(0)AT1 and SIT1. Some
      mutations of B(0)AT1 differentially interact with these accessory subunits,
      providing an explanation for differential intestinal phenotypes among Hartnup
      patients. The basolateral efflux of numerous amino acids from kidney tubular
      cells is mediated by heteromeric amino acid transporters that function as
      obligatory exchangers. Thus, other transporters within the same membrane need to
      mediate the net efflux of exchange substrates, controlling thereby the net
      basolateral amino transport and thus the intracellular amino acid concentration.

PMID- 19184092
TI  - Accelerated suicidal erythrocyte death in Klotho-deficient mice.
AB  - Klotho, a membrane protein mainly expressed in parathyroid glands, kidney, and
      choroid plexus, counteracts aging and increases the life span. Accordingly, life
      span is significantly shorter in Klotho-deficient mice (klotho(-/-)) than in
      their wild-type littermates (klotho(+/+)). The pleotropic effects of Klotho
      include inhibition of 1,25-dihydroxyvitamin D(3)(1,25(OH)(2)D(3)) formation.
      Vitamin D-deficient diet reverses the shortening of life span in klotho(-/-)
      mice. In a variety of cells, 1,25(OH)(2)D(3) stimulates Ca(2+) entry. In
      erythrocytes, increased Ca(2+) entry stimulates suicidal erythrocyte death, which
      is characterized by cell shrinkage and phosphatidylserine exposure at the
      erythrocyte surface. The present study explored the putative impact of Klotho on
      eryptosis. According to Fluo3 fluorescence, cytosolic Ca(2+) concentration was
      significantly larger in klotho(-/-) erythrocytes as compared to klotho(+/+)
      erythrocytes. According to annexin V-binding, phosphatidylserine exposure was
      significantly enhanced, and according to forward scatter, cell volume
      significantly decreased in klotho(-/-) erythrocytes as compared to klotho(+/+)
      erythrocytes. Energy depletion (13 h glucose depletion) and oxidative stress (35
      min 1 mM tert-butyl-hydroxyl-peroxide [tert-BOOH]) increased phosphatidylserine
      exposure to values again significantly larger in klotho(-/-) erythrocytes as
      compared to klotho(+/+) erythrocytes. Reticulocyte number was significantly
      increased in klotho (-/-) mice, pointing to enhanced erythrocyte turnover.
      Vitamin D-deficient diet reversed the enhanced Ca(2+) entry and annexin V-binding
      of klotho(-/-) erythrocytes. The present observations reveal a novel function of
      Klotho, i.e., the at least partially vitamin D-dependent regulation of cytosolic
      Ca(2+) activity in and suicidal death of erythrocytes.

PMID- 19184093
TI  - Atrial arrhythmogenesis in wild-type and Scn5a+/delta murine hearts modelling
      LQT3 syndrome.
AB  - Long QT(3) (LQT3) syndrome is associated with abnormal repolarisation kinetics,
      prolonged action potential durations (APD) and QT intervals and may lead to life
      threatening ventricular arrhythmias. However, there have been few physiological
      studies of its effects on atrial electrophysiology. Programmed electrical
      stimulation and burst pacing induced atrial arrhythmic episodes in 16 out of 16
      (16/16) wild-type (WT) and 7/16 genetically modified Scn5a+/Delta (KPQ)
      Langendorff-perfused murine hearts modelling LQT3 (P < 0.001 for both), and in
      14/16 WT and 1/16 KPQ hearts (P < 0.001 for both; Fisher's exact test),
      respectively. The arrhythmogenic WT hearts had significantly larger positive
      critical intervals (CI), given by the difference between atrial effective
      refractory periods (AERPs) and action potential durations at 90% recovery
      (APD(90)), compared to KPQ hearts (8.1 and 3.2 ms, respectively, P < 0.001).
      Flecainide prevented atrial arrhythmias in all arrhythmogenic WT (P < 0.001) and
      KPQ hearts (P < 0.05). It prolonged the AERP to a larger extent than it did the
      APD(90) in both WT and KPQ groups, giving negative CIs. Quinidine similarly
      exerted anti-arrhythmic effects, prolonged AERP over corresponding APD(90) in
      both WT and KPQ groups. These findings, thus, demonstrate, for the first time,
      inhibitory effects of the KPQ mutation on atrial arrhythmogenesis and its
      modification by flecainide and quinidine. They attribute these findings to
      differences in the CI between WT and mutant hearts, in the presence or absence of
      these drugs. Thus, prolongation of APD(90) over AERP gave positive CI values and
      increased atrial arrhythmogenicity whereas lengthening of AERP over APD(90)
      reduced such CI values and produced the opposite effect.

PMID- 19184094
TI  - Phytochrome A requires jasmonate for photodestruction.
AB  - The plant photoreceptor phytochrome is organised in a small gene family with
      phytochrome A (phyA) being unique, because it is specifically degraded upon
      activation by light. This so called photodestruction is thought to be important
      for dynamic aspects of sensing such as measuring day length or shading by
      competitors. Signal-triggered proteolytic degradation has emerged as central
      element of signal crosstalk in plants during recent years, but many of the
      molecular players are still unknown. We therefore analyzed a jasmonate (JA)
      deficient rice mutant, hebiba, that in several aspects resembles a mutant
      affected in photomorphogenesis. In this mutant, the photodestruction of phyA is
      delayed as shown by in vivo spectroscopy and Western blot analysis. Application
      of methyl-JA (MeJA) can rescue the delayed phyA photodestruction in the mutant in
      a time- and dose-dependent manner. Light regulation of phyA transcripts thought
      to be under control of stable phytochrome B (phyB) is still functional. The
      delayed photodestruction is accompanied by an elevated sensitivity of phytochrome
      dependent growth responses to red and far-red light.

PMID- 19184095
TI  - A novel fusion protein that functions as an enhanced green fluorescent protein
      reporter and a tetracycline-controlled transcriptional activator.
AB  - Binary expression systems are widely employed to analyze gene function in vivo
      using transgenic organisms. The tetracycline-off (Tet-Off) system, which is a
      binary expression system that uses a tetracycline-controlled transactivator
      protein (tTA) and its tetracycline operator sequence (tetO) binding site, was
      developed as a method for temporally controlling gene expression. To facilitate
      the use of the Tet-Off system in animal species other than the model organisms
      that are widely used for genetic analysis, we constructed two different fusion
      proteins containing enhanced green fluorescent protein (EGFP) as the reporter
      gene and tTA as the transactivator, in different configurations. We assessed the
      utility of these fusion proteins designated as tTA-EGFP and EGFP-tTA in
      transgenic fruit flies. We showed that, although EGFP of both fusion proteins was
      efficiently fluoresced, transcriptional activation occurred only by the tTA-EGFP
      fusion protein. Furthermore, tetracycline (Tc) and doxycycline (Dox) both
      effectively inactivated tTA-EGFP, repressing gene expression under tetO control
      in a concentration-dependent manner. Additionally, the removal of Tc or Dox from
      the diet can recover the transactivator activity of tTA-EGFP in a concentration-
      and time-dependent manner. The tTA-EGFP fusion protein will therefore be useful
      in the analysis of gene function in a wide range of animal species.

PMID- 19184096
TI  - The post-embryonic development of Remipedia (Crustacea)--additional results and
      new insights.
AB  - The post-embryonic development of a species of the enigmatic crustacean group
      Remipedia is described in detail for the first time under various aspects.
      Applying a molecular approach, we can clearly prove the species identity of the
      larvae as belonging to Pleomothra apletocheles. We document the cellular level of
      several larval stages and the differentiation of segments, limbs, and the general
      body morphology applying the techniques of confocal laser scanning microscopy and
      scanning electron microscopy. In addition, we document the swimming behavior and
      the peculiar movements of the naupliar appendages. A comparison of our results
      with published data on other Crustacea and their larval development tentatively
      supports ideas about phylogenetic affinities of the Remipedia to the
      Malacostraca.

PMID- 19184097
TI  - Further characterization of the PW peptide family that inhibits neuron
      differentiation in Hydra.
AB  - From an evolutionary point of view, Hydra has one of the most primitive nervous
      systems among metazoans. Two different groups of peptides that affect neuron
      differentiation were identified in a systematic screening of peptide signaling
      molecules in Hydra. Within the first group of peptides, a neuropeptide, Hym-355,
      was previously shown to positively regulate neuron differentiation. The second
      group of peptides encompasses the PW family of peptides that negatively regulate
      neuron differentiation. In this study, we identified the gene encoding PW peptide
      preprohormone. Moreover, we made the antibody that specifically recognizes LPW.
      In situ hybridization and immunohistochemical analyses showed that the PW
      peptides and the gene encoding them were expressed in ectodermal epithelial cells
      throughout the body except for the basal disk. The PW peptides are produced by
      epithelial cells and are therefore termed "epitheliopeptides." Together with Hym
      355, the PW family peptides mediate communication between neurons and epithelial
      cells and thereby maintain a specific density of neurons in Hydra.

PMID- 19184098
TI  - Conserved and novel gene expression between regeneration and asexual fission in
      Nematostella vectensis.
AB  - Due to work in model systems (e.g., flies and mice), the molecular mechanisms of
      embryogenesis are known in exquisite detail. However, these organisms are
      incapable of asexual reproduction and possess limited regenerative abilities.
      Thus, the mechanisms of alternate developmental trajectories and their relation
      to embryonic mechanisms remain understudied. Because these developmental
      trajectories are present in a diverse group of animal phyla spanning the metazoan
      phylogeny, including cnidarians, annelids, and echinoderms, they are likely to
      have played a major role in animal evolution. The starlet sea anemone
      Nematostella vectensis, an emerging model system, undergoes larval development,
      asexual fission, and complete bi-directional regeneration in the field and
      laboratory. In order to investigate to what extent embryonic patterning
      mechanisms are utilized during alternate developmental trajectories, we examined
      expression of developmental regulatory genes during regeneration and fission.
      When compared to previously reported embryonic expression patterns, we found that
      all genes displayed some level of expression consistent with embryogenesis.
      However, five of seven genes investigated also displayed striking differences in
      gene expression between one or more developmental trajectory. These results
      demonstrate that alternate developmental trajectories utilize distinct molecular
      mechanisms upstream of major developmental regulatory genes such as fox, otx, and
      Hox-like.

PMID- 19184099
TI  - RABGAP1L gene rearrangement resulting from a der(Y)t(Y;1)(q12;q25) in acute
      myeloid leukemia arising in a child with Klinefelter syndrome.
AB  - In this study, we report the molecular cytogenetic characterization of an acute
      myeloid leukemia with a der(Y)t(Y;1)(q12;q25) in bone marrow cells in a child
      with Klinefelter syndrome. Conventional cytogenetics demonstrated the unbalanced
      translocation, i.e., a trisomic 1q25-qter juxtaposed to Yq12 replaced the
      terminal segment of chromosome Y was acquired and present only on bone marrow
      cells. Fluorescence in situ hybridization showed that the breakpoint at 1q25
      disrupted RABGAP1L, a strongly expressed gene in CFU-GEMM, erythroid cells, and
      megakaryocytes, while the Yq12 breakpoint fell within the heterochromatic region.
      As der(Y)t(Y;1)(q12;q25) was an isolated cytogenetic change, RABGAP1L
      rearrangement as well as gene(s) dosage effects correlated to 1q25-qter trisomy,
      and Yq12-qter loss may make a major contribution to leukemogenesis and/or disease
      progression.

PMID- 19184100
TI  - Superior olivary complex organization and cytoarchitecture may be correlated with
      function and catarrhine primate phylogeny.
AB  - In the mammalian auditory system, the medial nucleus of the trapezoid body and
      the lateral superior olive (MNTB-LSO system) contribute to binaural intensity
      processing and lateralization. Localization precision varies with the sound
      frequencies. As recency of common ancestry with human beings increases, primates
      have improved low-frequency sensitivity and reduced sensitivity to higher
      frequencies. The medial part of the MNTB is devoted to higher frequency
      processing. Thus, its high-frequency-dependent function is nearly lost in humans
      and its role in binaural processing as part of the contralateral pathway to the
      LSO remains questionable. Here, Nissl-stained sections of the superior olivary
      complex of man (Homo sapiens), bonobo (Pan paniscus), chimpanzee (Pan
      troglodytes), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), gibbon
      (Hylobates lar), and macaque (Macaca fascicularis) were compared to reveal
      differences and coincidences. From chimpanzees to humans, the size of the LSO
      decreased, and the MNTB as a compact nucleus nearly disappears. From chimpanzees
      to humans, the LSO/MNTB ratio increases dramatically too, whereas the LSO/MSO
      ratio remains 1.1; a finding that probably corresponds to the phylogenetic
      proximity between the species.

PMID- 19184101
TI  - The influence of combined exercise training on indices of obesity, physical
      fitness and lipid profile in overweight and obese adolescents with mental
      retardation.
AB  - INTRODUCTION: This study investigated the effect of combined exercise training on
      indices of body composition, physical fitness and lipid profile in adolescents
      with mental retardation. MATERIALS AND METHODS: Thirty adolescents with mental
      retardation (total IQ, 45-70) received exercise training (n = 15) or no training
      (n = 15). Groups were matched for age, sex and mental retardation. Before and
      after the intervention period, indices of body composition, physical fitness and
      lipid profile were measured. RESULTS: In comparison with the control group,
      weight, body mass index, waist and fat mass decreased significantly, while
      relative fat-free mass increased. The level of triglycerides, total cholesterol
      and low-density lipoprotein decreased significantly, while high-density
      lipoprotein increased. Muscle strength, muscle fatigue resistance and sit-to
      stand were ameliorated. PeakVO2/peak power decreased significantly. The distance
      covered in the 6-min walk test (6MWT) increased with 50 m. CONCLUSION: In
      conclusion, combined exercise training has a positive effect on indices of
      obesity, physical fitness and lipid profile in adolescents with mental
      retardation.

PMID- 19184102
TI  - Nonalcoholic fatty liver disease during valproate therapy.
AB  - Valproic acid (VPA) is effective for the treatment of many types of epilepsy, but
      its use can be associated with an increase in body weight. We report a case of
      nonalcoholic fatty liver disease (NAFLD) arising in a child who developed obesity
      during VPA treatment. Laboratory data revealed hyperinsulinemia with insulin
      resistance. After the withdrawal of VPA therapy, our patient showed a significant
      weight loss, a decrease of body mass index, and normalization of metabolic and
      endocrine parameters; moreover, ultrasound measurements showed a complete
      normalization. The present case suggests that obesity, hyperinsulinemia, insulin
      resistance, and long-term treatment with VPA may be all associated with the
      development of NAFLD; this side effect is reversible after VPA withdrawal.

PMID- 19184105
TI  - In silico comparative genome analysis of malaria parasite Plasmodium falciparum
      and Plasmodium vivax chromosome 4.
AB  - Malarial parasite has long been a subject of research for a large community of
      scientists and has yet to be conquered. One of the main obstacles to effectively
      control this disease is rapidly evolving genetic structure of Plasmodium parasite
      itself. In this study, we focused on chromosome 4 of the Plasmodium falciparum
      and Plasmodium vivax species and carried out comparative studies of genes that
      are responsible for antigenic variation in respective species. Comparative
      analysis of genes responsible for antigenic variation (var and vir genes in P.
      falciparum and P. vivax, respectively) showed significant difference in their
      respective nucleotide sequence lengths as well as amino acid composition. The
      possible association of exon's length on pathogenecity of respective Plasmodium
      species was also investigated, and analysis of gene structure showed that on the
      whole, exon lengths in P. falciparum are larger compared to P. vivax. Analysis of
      tandem repeats across the genome has shown that the size of repetitive sequences
      has a direct effect on chromosomes length, which can also be a potential reason
      for P. falciparum's greater variability and hence pathogenecity than P. vivax.

PMID- 19184104
TI  - Alpha-fetoprotein and human telomerase reverse transcriptase mRNA levels in
      peripheral blood of patients with hepatocellular carcinoma.
AB  - PURPOSE: Tumor-associated gene expression in peripheral blood reflects the
      presence of circulating hepatocellular carcinoma (HCC) cells and might be
      associated with aggressive features of HCC. We assessed the prognostic
      significance of alpha-fetoprotein (AFP) and human telomerase reverse
      transcriptase protein (hTERT) mRNA expression in the peripheral blood of HCC
      patients. METHODS: About 343 HCC patients, treated at the National Cancer Center,
      Korea, were included in this study. We measured AFP and hTERT mRNA levels in
      peripheral blood using quantitative real-time reverse transcription polymerase
      chain reaction. The association between the expression of each gene and survival
      was analyzed. RESULTS: AFP and hTERT mRNA were detected in 204 (59.5%) and 48
      (14.0%) patients with HCC, respectively. The mean AFP copy number was 203
      copies/microL (range 0-19992 copies/microL) and that of hTERT was 26
      copies/microL (0-1711 copies/microL). AFP mRNA expression was correlated with the
      number of tumors (P = 0.05), but there were no significant association between
      hTERT expression and clinical features. There was also no relationship between
      overall survival and AFP (P = 0.08) or hTERT (P = 0.67) mRNA expression.
      CONCLUSIONS: This is the first report to evaluate the association between
      peripheral blood hTERT mRNA expression, and survival of HCC patients. The results
      indicate that AFP and hTERT mRNA expression in peripheral blood may not be useful
      HCC prognostic markers.

PMID- 19184106
TI  - Screening of different classes of proteases in microfilarial and adult stages of
      Setaria cervi.
AB  - Many of the filarial proteases involved in critical physiological functions are
      expressed in stage-specific manner and belong to various mechanistic classes.
      Setaria cervi, a bovine filarial parasite express different classes of proteases.
      This parasite shows strong antigenic cross-reactivity with human filarial
      parasites Wuchereria bancrofti and Brugia malayi. Somatic extracts of S. cervi
      microfilariae (mf) and adult stages as well as their excretory-secretory (ES)
      products were screened for the presence of different classes of proteases using
      general (casein, bovine hemoglobin) and class specific substrates. Detergent
      soluble extracts of male and female worms were also screened. Significant enzyme
      activity was detected in ES products both at pH 5.0 and 7.0 with casein.
      Cathepsin B-like activity was found to be much higher in membrane-bound extract
      than in the crude-soluble extract. However, it was also found to be actively
      secreted by both mf and adult worms. Cathepsin D-like activity assayed at pH 3.0
      was very low both in somatic extract as well as in ES products. Collagenase
      activity at neutral pH showed higher levels, both in somatic extract and ES
      products. Cathepsin L-like activity was detected only in crude-soluble extract
      but was below detectable limit in ES products. Leucine aminopeptidase activity
      was significant both in crude-soluble extract and ES products. This study, thus,
      might be helpful for a better understanding of host-parasite interaction and
      identification of appropriate virulence factors that may be targeted as vaccine
      and/or drug targets against lymphatic filariasis.

PMID- 19184107
TI  - Expression diversity and evolutionary dynamics of rice duplicate genes.
AB  - Duplicate genes are believed to be a major source of new gene functions over
      evolutionary time. In order to evaluate the evolutionary dynamics of rice
      duplicate genes, formed principally by paleoployploidization prior to the
      speciation of the Poaceae family, we have employed a public microarray dataset
      including 155 gene expression omnibus sample plates and bioinformatics tools. At
      least 57.4% of old approximately 70 million years ago (MYA) duplicate gene pairs
      exhibit divergences in expression over the given experimental set, whereas at
      least 50.9% of young approximately 7.7-MYA duplicate gene pairs were shown to be
      divergent. When grouping the rice duplicate genes according to functional
      categories, we noted a striking and significant enrichment of divergent duplicate
      metabolism-associated genes, as compared to that observed in non-divergent
      duplicate genes. While both non-synonymous substitution (Ka) and synonymous
      substitution (Ks) values between non- and divergent duplicate gene pairs
      evidenced significant differences, the Ka/Ks values between them exhibited no
      significant differences. Interestingly, the average numbers of conserved motifs
      of the duplicate gene pairs revealed a pattern of decline along with an increase
      in expression diversity, partially supporting the subfunctionalization model with
      degenerative complementation in regulatory motifs. Duplicate gene pairs with high
      local similarity (HLS) segments, which might be formed via conversion between
      rice paleologs, evidenced higher expression correlations than were observed in
      the gene pairs without the HLS segments; this probably resulted in an increased
      likelihood of gene conversion in promoters of the gene pairs harboring HLS
      segments. More than 30% [corrected] of the rice gene families exhibited similar
      high expression diversity between members as compared to that of randomly
      selected gene pairs. These findings are likely reflective of the evolutionary
      dynamics of rice duplicate genes for gene retention.

PMID- 19184109
TI  - Pyruvate dehydrogenase phosphatase 1 (PDP1) null mutation produces a lethal
      infantile phenotype.
AB  - Pyruvate dehydrogenase phosphatase deficiency has previously only been confirmed
      at the molecular level in two brothers and two breeds of dog with exercise
      intolerance. A female patient, who died at 6 months, presented with lactic
      acidemia in the neonatal period with serum lactate levels ranging from 2.5 to 17
      mM. Failure of dichloroacetate to activate the PDH complex in skin fibroblasts
      was evident, but not in early passages. A homozygous c.277G > T (p.E93X) nonsense
      mutation in the PDP1 gene was identified in genomic DNA and immunoblotting showed
      a complete absence of PDP1 protein in mitochondria. Native PDHC activity could be
      restored by the addition of either recombinant PDP1 or PDP2. This highlights the
      role of PDP2, the second phosphatase isoform, in PDP1-deficient patients for the
      first time. We conclude that the severity of the clinical course associated with
      PDP1 deficiency can be quite variable depending on the exact nature of the
      molecular defect.

PMID- 19184108
TI  - Mutation screening of apical sodium-dependent bile acid transporter (SLC10A2):
      novel haplotype block including six newly identified variants linked to reduced
      expression.
AB  - The apical sodium-dependent bile acid transporter (SLC10A2) plays a key role in
      the reabsorption of luminal bile acids into the enterohepatic circulation. Rare
      variations in SLC10A2 have been reported to be associated with Crohn's disease,
      primary bile acid malabsorption and familial hypertriglyceridemia; however,
      variants associated with reduced SLC10A2 expression have not been reported to
      date. In this study, we have performed a sequence analysis of SLC10A2 using
      genomic DNA of 93 individuals. A new haplotype structure was identified including
      ten variants with complete linkage disequilibrium (LD' = 1.0, r (2) = 1.0) of
      which six polymorphisms were novel. The sequence variants were confirmed in three
      independent cohorts (n = 1,290) by a recently established MALDI-TOF MS iPLEX
      assay. Remarkably, haplotype carriers with the minor allele exhibited significant
      reduced ileal SLC10A2 expression on mRNA levels (2.6-fold, P = 0.0009) and
      protein levels (2.4-fold, P = 0.0157). In future studies a single tag SNP
      selected of this haplotype block will provide reliable genetic testing to
      investigate systemically the influence of the SLC10A2 haplotype for disease
      susceptibility and/or drug response.

PMID- 19184110
TI  - Truncating loss-of-function mutations of DISP1 contribute to holoprosencephaly
      like microform features in humans.
AB  - Defective function of the Sonic Hedgehog (SHH) signaling pathway is the most
      frequent alteration underlying holoprosencephaly (HPE) or its various clinical
      microforms. We performed an extensive mutational analysis of the entire human
      DISP1 gene, required for secretion of all hedgehog ligand(s) and which maps to
      the HPE 10 locus of human chromosome 1q41, as a HPE candidate gene. Here, we
      describe two independent families with truncating mutations in human DISP1 that
      resemble the cardinal craniofacial and neuro-developmental features of a recently
      described microdeletion syndrome that includes this gene; therefore, we suggest
      that DISP1 function contributes substantially to both of these signs in humans.
      While these clinical features are consistent with common HPE microforms,
      especially those linked to defective signaling by Sonic Hedgehog, we have
      insufficient evidence so far that functionally abnormal DISP1 alleles will
      commonly contribute to the more severe features of typical HPE.

PMID- 19184111
TI  - Use of weighted reference panels based on empirical estimates of ancestry for
      capturing untyped variation.
AB  - Many association methods use a subset of genotyped single nucleotide
      polymorphisms (SNPs) to capture or infer genotypes at other untyped SNPs. We and
      others previously showed that tag SNPs selected to capture common variation using
      data from The International HapMap Consortium (Nature 437:1299-1320, 2005), The
      International HapMap Consortium (Nature 449:851-861, 2007) could also capture
      variation in populations of similar ancestry to HapMap reference populations (de
      Bakker et al. in Nat Genet 38:1298-1303, 2006; Gonzalez-Neira et al. in Genome
      Res 16:323-330, 2006; Montpetit et al. in PLoS Genet 2:282-290, 2006; Mueller et
      al. in Am J Hum Genet 76:387-398, 2005). To capture variation in admixed
      populations or populations less similar to HapMap panels, a "cosmopolitan
      approach," in which all samples from HapMap are used as a single reference panel,
      was proposed. Here we refine this suggestion and show that use of a "weighted
      reference panel," constructed based on empirical estimates of ancestry in the
      target population (relative to available reference panels), is more efficient
      than the cosmopolitan approach. Weighted reference panels capture, on average,
      only slightly fewer common variants (minor allele frequency > 5%) than the
      cosmopolitan approach (mean r (2) = 0.977 vs. 0.989, 94.5% variation captured vs.
      96.8% at r (2) > 0.8), across the five populations of the Multiethnic Cohort, but
      entail approximately 25% fewer tag SNPs per panel (average 538 vs. 718). These
      results extend a recent study in two Indian populations (Pemberton et al. in Ann
      Hum Genet 72:535-546, 2008). Weighted reference panels are potentially useful for
      both the selection of tag SNPs in diverse populations and perhaps in the design
      of reference panels for imputation of untyped genotypes in genome-wide
      association studies in admixed populations.

PMID- 19184112
TI  - Identification of susceptibility genes for complex diseases using pooling-based
      genome-wide association scans.
AB  - The success of genome-wide association studies (GWAS) to identify risk loci of
      complex diseases is now well-established. One persistent major hurdle is the cost
      of those studies, which make them beyond the reach of most research groups.
      Performing GWAS on pools of DNA samples may be an effective strategy to reduce
      the costs of these studies. In this study, we performed pooling-based GWAS with
      more than 550,000 SNPs in two case-control cohorts consisting of patients with
      Type II diabetes (T2DM) and with chronic rhinosinusitis (CRS). In the T2DM study,
      the results of the pooling experiment were compared to individual genotypes
      obtained from a previously published GWAS. TCF7L2 and HHEX SNPs associated with
      T2DM by the traditional GWAS were among the top ranked SNPs in the pooling
      experiment. This dataset was also used to refine the best strategy to correctly
      identify SNPs that will remain significant based on individual genotyping. In the
      CRS study, the top hits from the pooling-based GWAS located within ten kilobases
      of known genes were validated by individual genotyping of 1,536 SNPs. Forty-one
      percent (598 out of the 1,457 SNPs that passed quality control) were associated
      with CRS at a nominal P value of 0.05, confirming the potential of pooling-based
      GWAS to identify SNPs that differ in allele frequencies between two groups of
      subjects. Overall, our results demonstrate that a pooling experiment on high
      density genotyping arrays can accurately determine the minor allelic frequency as
      compared to individual genotyping and produce a list of top ranked SNPs that
      captures genuine allelic differences between a group of cases and controls. The
      low cost associated with a pooling-based GWAS clearly justifies its use in
      screening for genetic determinants of complex diseases.

PMID- 19184113
TI  - New insights into autophagic cell death in the gypsy moth Lymantria dispar: a
      proteomic approach.
AB  - Autophagy is an evolutionary ancient process based on the activity of genes
      conserved from yeast to metazoan taxa. Whereas its role as a mechanism to provide
      energy during cell starvation is commonly accepted, debate continues about the
      occurrence of autophagy as a means specifically activated to achieve cell death.
      The IPLB-LdFB insect cell line, derived from the larval fat body of the
      lepidoptera Lymantria dispar, represents a suitable model to address this
      question, as both autophagic and apoptotic cell death can be induced by various
      stimuli. Using morphological and functional approaches, we have observed that the
      culture medium conditioned by IPLB-LdFB cells committed to death by the ATPase
      inhibitor oligomycin A stimulates autophagic cell death in untreated IPLB-LdFB
      cells. Moreover, proteomic analysis of the conditioned media suggests that, in
      IPLB-LdFB cells, oligomycin A promotes a shift towards lipid metabolism,
      increases oxidative stress and specifically directs the cells towards autophagic
      activity.

PMID- 19184115
TI  - Xylose reductase activity in Debaryomyces hansenii UFV-170 cultivated in semi
      synthetic medium and cotton husk hemicellulose hydrolyzate.
AB  - To develop a new enzymatic xylose-to-xylitol conversion, deeper knowledge on the
      regulation of xylose reductase (XR) is needed. To this purpose, a new strain of
      Debaryomyces hansenii (UFV-170), which proved a promising xylitol producer, was
      cultivated in semi-synthetic media containing different carbon sources,
      specifically three aldo-hexoses (D-glucose, D-galactose and D-mannose), a keto
      hexose (D-fructose), a keto-pentose (D-xylose), three aldo-pentoses (D-arabinose,
      L-arabinose and D-ribose), three disaccharides (maltose, lactose and sucrose) and
      a pentitol (xylitol). The best substrate was lactose on which cell concentration
      reached about 20 g l(-1) dry weight (DW), while the highest specific growth rates
      (0.58-0.61 h(-1)) were detected on lactose, D-mannose, D-glucose and D-galactose.
      The highest specific activity of XR (0.24 U mg(-1)) was obtained in raw extracts
      of cells grown on D-xylose and harvested in the stationary growth phase. When
      grown on cotton husk hemicellulose hydrolyzates, cells exhibited XR activities
      five to seven times higher than on semi-synthetic media.

PMID- 19184116
TI  - The co-existence of membranoproliferative glomerulonephritis type 1 and coeliac
      disease: a case report.
AB  - Coeliac disease is an autoimmune enteropathy characterised by chronic
      inflammation of the small intestinal mucosa and the presence of typical
      autoantibodies. Coeliac disease may be a risk factor for renal disease.
      Immunoglobulin A (IgA) nephropathy is reported in the majority of these cases.
      Only one adult patient had been reported with membranoproliferative
      glomerulonephritis (MPGN) and coeliac disease. Here, we report a case in a 12
      year-old girl with coeliac disease who presented with severe anaemia and later
      developed nephrotic syndrome. Renal biopsy of the patient was consistent with
      MPGN type 1, which has not been previously reported in children with coeliac
      disease. A gluten-free diet was started. After 6 months of this diet, her
      nephrotic syndrome resolved completely. This case is presented to draw attention
      to the rare association of coeliac disease and MPGN type 1.

PMID- 19184117
TI  - Circadian rhythms of diuresis, proteinuria and natriuresis in children with
      chronic glomerular disease.
AB  - The aim of our study was to examine diurnal variation in urine volume (UV)
      output, proteinuria (UPRT), urine creatinine (UCr) and urine sodium ion excretion
      (UNa) in children with chronic glomerulopathy. In 56 patients (20 boys/36 girls,
      aged 11.7 +/- 0.6 years) samples for UPRT, UCr and UNa were collected during the
      day and night, with continuous ambulatory blood pressure (BP) monitoring. On the
      basis of creatinine clearance (CrCl) the patients were divided into group I (n =
      44, with CrCl 131 +/- 3.6 ml/min per 1.73 m(2) body surface area), or group II (n
      = 12, with CrCl 44.6 +/- 7.7 ml/min per 1.73 m(2) body surface area). Nocturnal
      polyuria was defined as night time UV >or= 35% of the 24 h UV. Age, gender, body
      mass index of the patients, 24 h UV, UCr and UNa were similar in both groups.
      However, arterial hypertension and nocturnal polyuria were widespread (P < 0.01)
      in group II. In addition, proteinuria was higher (P < 0. 05) in group II. The
      nocturnal decline in CrCl, UV, UPRT and UNa was significantly attenuated (P <
      0.005) in patients in group II compared with those in group I. The night time
      mean arterial pressure (MAP), as well as the night/day ratios of MAP, UV, UPRT
      and UNa, showed negative associations with CrCl. Our findings strongly suggest
      that renal function diurnal variation and nocturnal MAP are related to decreased
      glomerular filtration rate at the time of examination.

PMID- 19184118
TI  - Streptococcal zymogen type B induces angiotensin II in mesangial cells and
      leukocytes.
AB  - Previous reports have shown that angiotensin II and oxidative stress may be
      important features in acute poststreptococcal glomerulonephritis (APSGN) and that
      streptococcal erythrogenic toxin type B (ETB) and its precursor (ETBP) may have
      an important role in the pathogenesis of APSGN. The aim of this study was to
      determine the effect of ETBP on the production of angiotensin II and oxidative
      stress in rat mesangial cells and human mononuclear leukocytes. Mesangial cells
      and leukocytes were isolated from digested glomeruli and by histopaque gradient,
      respectively, while ETBP was isolated from nephritogenic streptococcus cultures
      using a cation exchange column. Angiotensin II was determined by an enzyme-linked
      immunosorbent assay and by cytometrics. Superoxide anion, reduced glutathione,
      nitrites, lipid peroxidation and catalase activity were determined by
      cytochemical, biochemical and enzymatic assays. Inducible nitric oxide synthase
      expression was determined by cytometrics. An increased production of angiotensin
      II was observed in ETBP-treated mesangial cell and leukocyte cultures. The ETBP
      induced an elevated production of superoxide anions and nitrites in mesangial
      cells and superoxide anions in leukocytes, while this streptococcal protein
      decreased the expression of inducible nitric oxide synthase in leukocytes. The
      ETBP was capable of inducing an increased production of angiotensin II and
      increased oxidative stress, both of which may be important mediators of
      inflammatory events in the renal tissue and during APSGN.

PMID- 19184119
TI  - Sensitivity of ultrasonography in detecting renal parenchymal defects: 6 years'
      follow-up.
AB  - While (99m)Tc-dimercaptosuccinic acid (DMSA) scanning is still considered the
      most accurate method for the assessment of renal parenchymal defects (RPDs), our
      study 6 years previously suggested that ultrasonography (US) could be a safe and
      efficient substitute for this purpose, provided that it is reliably performed and
      that renal function parameters are followed. By comparison of the original and
      follow-up study data from 67 children, the accuracy of our recommendations was re
      evaluated. US was performed and renal function parameters investigated and
      correlated to the DMSA scans from the original study. US identified all six
      patients with clinically significant RPD and 52/61 with clinically insignificant
      RPDs, seen on the DMSA scans. Twenty two out of 22 severe RPDs, 21/23 moderate
      RPDs and 20/40 mild RPDs seen on the DMSA scans were detected by US. In ten cases
      normal US findings from the original study were rendered abnormal, correlating
      well with the DMSA scans with respect to RPD localization and kidney size. These
      results further support our previous suggestion that US is a safe and harmless
      alternative to DMSA scanning in the detection and follow-up of RPDs. While it
      cannot be excluded that small RPDs missed on the initial US might 'develop'
      clinical significance in later life, children with normal findings on initial US
      should have another sonogram done, at the shortest a year later, together with an
      investigation of renal function parameters.

PMID- 19184120
TI  - Common variants of the glial cell-derived neurotrophic factor gene do not
      influence kidney size of the healthy newborn.
AB  - Glial cell-derived neurotrophic factor (GDNF) plays an important role in renal
      development, serving as a trophic factor for outgrowth of the ureteric bud and
      its continued arborisation. Our previous studies have shown that common variants
      of the human paired-box 2 (PAX2) gene (a transcriptional activator of GDNF) and
      rearranged during transfection (RET) gene (encoding the cognate receptor for
      GDNF) are associated with a subtle reduction in the kidney size of newborns.
      Since heterozygosity for a mutant GDNF allele causes mild renal hypoplasia and
      modest hypertension in mice, we considered the possibility that common variants
      of the GDNF gene might also contribute to renal hypoplasia in humans. We studied
      the relationship between newborn renal size or umbilical cord cystatin C and 19
      common GDNF gene variants [minor allele frequency (MAF) >5%], three single
      nucleotide polymorphisms (SNPs) related to a putative PAX binding site and one
      rare SNP (rs36119840 A/G) which changes an amino acid (R93W), based on data from
      the haplotype map of the human genome (HapMap). However, none of these 23 SNPs
      was associated with reduced newborn kidney size or function. Among the 163
      Caucasians in our cohort, none had the R93W allele.

PMID- 19184121
TI  - [Procedure for certification of QST laboratories].
AB  - Quantitative sensory testing (QST) is the standardized assessment of the
      somatosensory system comprising all sensory submodalities. In the German Research
      Network on Neuropathic Pain (DFNS), a QST-battery consisting of 13 parameters has
      been established and nationwide normative data have been collected. In contrast
      to conventional electrophysiology, QST allows detecting negative and positive
      sensory signs of both large and small fiber systems. However, as a subjective
      psychophysical method it is critically dependent on patients'/healthy subjects'
      cooperation thus strictly standardized protocols and instructions are needed to
      allow across laboratory comparisons. To facilitate more widespread use of QST,
      the German Pain Society (DGSS) and the DFNS have initiated a certification
      procedure for QST quality standards. Therefore, structural, procedural criteria
      and outcome parameters were establishd and are hereby presented. By maintaining
      high quality standards, the certification of QST is intended to contribute to a
      better understanding of the mechanisms behind neuropathic pain syndromes and
      thereby improve patient care as well as sensory assessment in clinical studies on
      the treatment of neuropathic pain syndromes.

PMID- 19184122
TI  - Effect of hot temperatures on the hematological parameters, health and
      performance of calves.
AB  - The objective of this paper was to evaluate the effects of high temperatures on
      calves. The hypothesis that the red and white blood cells, health, and
      performance of calves would be influenced by the temperature period at birth and
      gender was tested. Sixty-three Holstein calves were used. They were reared in
      individual hutches from the second day of life to weaning at the age of 8 weeks.
      All calves were allotted to treatment groups according to the temperature period
      at birth: moderate temperature period 1 (MT1), high temperature period (HT),
      moderate temperature period 2 (MT2). The same conditions of nutrition were
      ensured. We recorded 62 summer days and 14 tropical days during HT. Sixty-six
      days with a value above 72.0 of the temperature-humidity index (THI) and 26 with
      values greater than 78.0 were found. No significant differences were found in red
      blood cells with the exception of hemoglobin between MT1 and MT2 (p = 0.031)
      during the 8th week. Significant differences were observed among treatment groups
      in the percentage of eosinophiles during the 6th week (p = 0.044). The HT calves
      had the least body weight from the first week to weaning (p = 0.053) and the
      highest water consumption (p = 0.042). The results emphasize the ability of dairy
      calves to maintain homeostasis during prolonged periods of heat stress. The
      exposure to high temperatures resulted only in a significant decrease of starter
      concentrate consumption and reduced growth.

PMID- 19184123
TI  - Retrospective evaluation of weekly paclitaxel hypersensitivity reactions reported
      utilizing an electronic medical record system at a tertiary cancer center.
AB  - OBJECTIVES: This is a retrospective observational study evaluating
      hypersensitivity reactions captured by an electronic medical record (EMR) system
      for weekly paclitaxel infusions. MATERIALS AND METHODS: The study evaluates the
      demographics, co-morbidities, premedications, chemotherapy agents, and
      postmedications of patients reporting a hypersensitivity reaction to weekly
      infusions of paclitaxel at a major cancer center, from June 2006 to December
      2007. Data were analyzed using descriptive statistics and logistic regression. P
      values <0.05 were considered significant. RESULTS: There were 51 hypersensitivity
      reactions in 36 patients during this time period that were documented in the
      allergy section of the EMR. Reactions occurred in patients with an average age of
      55 years (SD = 10.77); 47 (92%) of the reactions occurred in females, and 42
      (82%) of the reactions occurred with orders on the breast medical/surgical
      service. Thirty-two (63%) reactions occurred with either the first or second dose
      of weekly paclitaxel infusion. The most common premedication was dexamethasone
      (50 infusions), followed by diphenhydramine (18 infusions), and cimetidine (14
      infusions). Thirty-three (65%) infusions had only one premedication.
      Postreaction, 41 (80%) cases had diphenhydramine and 30 (59%) cases had
      hydrocortisone administered prior to restarting the infusion. Logistic regression
      analysis did not indicate any relationship between history of previous allergies,
      hypertension, coronary disease, or chronic obstructive pulmonary disease and the
      number of premedications. CONCLUSIONS: The results indicate that there is
      substantial variability in the type and number of premedications utilized in the
      management of paclitaxel hypersensitivity reactions. Interventions are needed to
      decrease the rate of hypersensitivity reactions from weekly paclitaxel infusions.

PMID- 19184124
TI  - Continued success of the rapid response radiotherapy program: a review of 2004
      2008.
AB  - PURPOSE: To update the clinical activity of the Rapid Response Radiotherapy
      Program (RRRP). MATERIALS AND METHODS: We conducted a retrospective review of our
      clinic database from January 2004 until July 2008. The number of patients
      referred to the RRRP, relevant demographic data, diagnosis and treatment
      dispositions were recorded. Time interval between referral to consultation and
      consultation to simulation were also calculated. RESULTS: During the study
      period, 3,267 patients were seen in the RRRP. Forty-five percent (1,494) of the
      patients were new to the clinic. Of the 3,267 patients seen, 1,548 (47.4%) were
      female and 1,719 (52.6%) were male. The median age was 69.2 years (range, 22-101
      years). The most common primary sites were lung (34.2%), breast (21.2%) and
      prostate (17.0%). The majority of patients were referred for palliative treatment
      of bone metastases (52.4%) or treatment for brain metastases (20.7%). Of the
      patients referred, 2,311 (70.5%) patients received palliative radiotherapy. The
      median duration from referral to consultation was 4 days. The majority (82.3%) of
      patients were simulated and treated within the first 7 days following
      consultation. CONCLUSION: The number of patients referred to the RRRP from
      January 2004-July 2008 remains comparable to our previous report (1996-2003). The
      overall median interval from referral to consultation for the analysed time
      period was 4 days. Therefore, we are continuing to meet our goal of providing
      rapid access to palliative radiation treatment for symptomatic cancer patients.
      Further information relating to progression and advancements within the clinic
      aimed at improving our patients' quality of life are explored.

PMID- 19184125
TI  - Soluble transferrin receptor and depth of bone marrow suppression following high
      dose chemotherapy.
AB  - BACKGROUND: Soluble transferrin receptor (sTfR) reflects erythropoietic activity
      in the bone marrow. We have sought to identify whether serial measurement of sTfR
      may predict depth or duration of myelosuppression in patients receiving high dose
      chemotherapy. MATERIALS AND METHODS: We prospectively measured serial sTfR in
      nine consecutive patients with haematologic malignancy admitted for various high
      dose regimens. The sTfR nadir was associated with white cell nadir, and sTfR
      nadir and day 5 sTfR were inversely associated with the number of red cell
      transfusions required. CONCLUSION: Our data suggest that sTfR may be helpful in
      predicting the degree of bone marrow suppression in patients receiving intensive
      chemotherapy.

PMID- 19184126
TI  - Symptom clusters in patients with advanced cancers.
AB  - GOALS OF WORK: It has been observed that certain cancer symptoms frequently occur
      together. Prior research on symptom patterns has focused mainly on inpatients,
      early stage cancers, or a single cancer type or metastatic site. Our aim was to
      explore symptom clusters among outpatients with different advanced cancers.
      MATERIALS AND METHODS: Symptom scores by the Edmonton Symptom Assessment Scale
      (ESAS) were routinely collected for patients attending the Oncology Palliative
      Care Clinics at Princess Margaret Hospital from January 2005 to October 2007.
      Principal component analysis (PCA) was performed for the entire patient cohort
      and within specific disease sites to determine inter-relationships of the nine
      ESAS symptoms. MAIN RESULTS: A total of 1,366 patients was included: 682 (50%)
      were male and 684 (50%) were female. The median age was 64 years (range 18 to 74
      years). The most common primary cancer sites were gastrointestinal (27%), lung
      (14%), and breast (11%). The three most distressful symptoms were fatigue, poor
      general well-being, and decreased appetite. PCA of symptoms for the entire
      patient cohort revealed two major symptom clusters: cluster 1 included fatigue,
      drowsiness, nausea, decreased appetite, and dyspnea, which accounted for 45% of
      the total variance; cluster 2 included anxiety and depression, which accounted
      for 10% of the total variance. There was high internal reliability in the
      clusters (Cronbach's alpha coefficient approximately 0.80). PCA of symptoms
      within the various primary cancer sites revealed differences in the pattern of
      symptom clusters. CONCLUSIONS: In patients with advanced cancers, distinct
      symptom clusters can be identified, which are influenced by primary cancer site.
      Treatments directed at symptom clusters rather than individual symptoms may
      provide greater therapeutic benefit. Further prospective studies are warranted in
      order to develop more effective targeted palliative interventions for the
      advanced cancer patient population.

PMID- 19184127
TI  - The existential experiences of receiving soft tissue massage in palliative home
      care--an intervention.
AB  - BACKGROUND: Soft tissue massage is currently used in palliative care for the
      relief of anxiety and pain. Only few studies have focused on patients' deeper
      experience of receiving the massage. AIM: The purpose of this study was to
      explore how patients with cancer in palliative home care experienced soft tissue
      massage. MATERIALS AND METHODS: Twenty-two patients received soft tissue massage
      (hand or foot) nine times over a period of 2 weeks. Each session lasted for 25
      min. Following the last massage session, a qualitative interview was conducted.
      The analysis was performed using a hermeneutic approach. FINDINGS: Soft tissue
      massage generated feelings of existential respite with perceptions of being
      released from illness for a while. Two categories constituted the basis of the
      experiences: (1) "an experience of thoughtful attention" and (2) "a sensation of
      complete tranquility" resulting in the overarching theme "A time of existential
      respite." CONCLUSION: The patients experienced the massage to give meaning and to
      be important as it generated feelings of an inner respite. RELEVANCE TO CLINICAL
      PRACTICE: Soft tissue massage appears to be an appreciated source of support to
      dying patients in palliative home care. The method is easy to comprehend and
      relatively short (25 min) which may imply that it is a suitable complement in
      nursing care for this patient group.

PMID- 19184128
TI  - Mycorrhizal status of plant species in the Chaco Serrano Woodland from central
      Argentina.
AB  - We examined the mycorrhizal type of 128 plant species in two patches of native
      vegetation of the Chaco Serrano Woodland, central Argentina, the largest dry
      forest area in South America. Of the 128 plant species investigated (belonging to
      111 genera in 53 families), 114 were colonized by arbuscular mycorrhizal fungi
      (AM), orchid mycorrhizal associations were present in the five terrestrial orchid
      species analyzed, one ectomycorrhiza was only present in Salix humboldtiana
      Willd., and 96 harbored a dark septate endophyte (DSE) association. Co-occurrence
      of AM and DSE was observed in 88 plant species. We determine morphological types
      of arbuscular mycorrhizal fungi (Arum, Paris, and intermediate AM structures) and
      report the mycorrhizal status in 106 new species, 12 of which are endemic to
      central Argentina and two, Aa achalensis Schltr. and Buddleja cordobensis
      Griseb., are declared to be vulnerable species. Root colonization in the Chaco
      Serrano Woodland is widespread and should be considered in revegetation programs
      due to the deterioration of this particular ecosystem. Considering the
      predominance of AM and DSE associations and the various potential benefits that
      these associations may bring to plant establishment, they should receive special
      attention in conservation and reforestation of these woodlands.

PMID- 19184129
TI  - Cervical epidural abscess and vertebral osteomyelitis following non-traumatic
      oesophageal rupture: a case report and discussion.
AB  - We present the case of a 62-year-old gentleman who presented with an epidural
      abscess and vertebral osteomyelitis secondary to a spontaneous rupture of the
      oesophagus. The causative organisms were Candida and Lactobacillus. This has not
      been recorded previously in the literature. Cases of vertebral osteomyelitis and
      epidural abscess secondary to oesophageal rupture are rare, and diagnosis is
      often delayed.

PMID- 19184130
TI  - Effect of metal ion substitutions in anticoagulation factor I from the venom of
      Agkistrodon acutus on the binding of activated coagulation factor X and on
      structural stability.
AB  - Anticoagulation factor I (ACF I) isolated from the venom of Agkistrodon acutus is
      an activated coagulation factor X (FXa)-binding protein that binds in a Ca(2+)
      dependent fashion with marked anticoagulant activity. The thermodynamics of the
      binding of alkaline earth metal ions to ACF I and the effects of alkaline earth
      metal ions on the guanidine hydrochloride (GdnHCl)-induced unfolding of ACF I and
      the binding of ACF I to FXa were studied by isothermal titration calorimetry,
      fluorescence, circular dichroism, and surface plasmon resonance, respectively.
      The results indicate that the ionic radii of the cations occupying Ca(2+)-binding
      sites in ACF I crucially affect the binding affinity of ACF I for alkaline earth
      metal ions as well as the structural stability of ACF I against GdnHCl
      denaturation. Sr(2+) and Ba(2+), with ionic radii larger than the ionic radius of
      Ca(2+), can bind to Ca(2+)-free ACF I (apo-ACF I), while Mg(2+), with an ionic
      radius smaller than that of Ca(2+), shows significantly low affinity for the
      binding to apo-ACF I. All bindings of Ca(2+), Sr(2+), and Ba(2+) ions in two
      sites of ACF I are mainly enthalpy-driven and the entropy is unfavorable for
      them. Sr(2+)-stabilized ACF I exhibits slightly lower resistance to GdnHCl
      denaturation than Ca(2+)-ACF I, while Ba(2+)-stabilized ACF I exhibits much lower
      resistance to GdnHCl denaturation than Ca(2+)-ACF I. Mg(2+) and Sr(2+), with
      ionic radii close to that of Ca(2+), can bind to FXa and therefore also induce
      the binding of ACF I to FXa, whereas Ba(2+), with a much larger ionic radius than
      Ca(2+), cannot support the binding of ACF I with FXa. Our observations suggest
      that bindings of Ca(2+), Sr(2+), and Ba(2+) ions in two sites of ACF I increase
      the structural stability of ACF I, but these bindings are not essential for the
      binding of ACF I with FXa, and that the binding of Mg(2+), Ca(2+), and Sr(2+)
      ions to FXa may be essential for the recognition between FXa and ACF I.

PMID- 19184131
TI  - Insight into the copper coordination environment in the prion protein through
      density functional theory calculations of EPR parameters.
AB  - Density functional theory (DFT) calculations of Cu(II) electron paramagnetic
      resonance (EPR) parameters for the octarepeat unit of the prion protein were
      conducted. Model complexes were constructed and optimized using the crystal
      structure of the octarepeat unit of the prion protein. Copper g and A tensors and
      nitrogen hyperfine and quadrupole coupling constants were calculated using DFT.
      Solvent effects were incorporated using the conductor-like screening model as
      well as through the inclusion of explicit water molecules. Calculations using the
      model with an additional axial water molecule added to the coordination sphere of
      the Cu(II) metal center give the best qualitative agreement for the copper g and
      A tensors. The S-band experimental EPR spectra were interpreted in light of the
      DFT calculations of the directly coordinated nitrogen hyperfine coupling
      constants which indicate that the three directly coordinated nitrogen atoms in
      the octarepeat unit are not equivalent. These results demonstrate that DFT
      calculations of EPR parameters can provide important insight with respect to the
      structural interpretation of experimental EPR data.

PMID- 19184132
TI  - Formation and isomerization of dicyclopenta[de,mn]anthracene. Electronic
      structure study.
AB  - The formation of dicyclopenta[de,mn]anthracene (P1) and its isomerization into
      dicyclopenta[jk,mn]phenanthrene (P3) was investigated using density functional
      theory. It was shown that P1 is formed from 1,4-diethynilanthracene, but due to
      its instability, it undergoes further transformation. This transformation
      involves rearrangements of some hydrogen atoms and ring contraction/ring
      expansion process, yielding as a final product the isomer P3. The energies of
      activation for the P1-->P3 intraconversion show that this reaction is competitive
      to the other, previously investigated isomerization of P1 into
      dicyclopenta[de,kl]anthracene (P2). In addition, our investigation shows that the
      formation of P3 from P1 is energetically more favorable than the formation of P3
      from P2. Thus, the presence of the isomer P3 in the reaction mixtures could also
      be caused by the isomerization of the very unstable isomer P1.

PMID- 19184133
TI  - Infratemporal fossa myoepithelial carcinoma--a rare case report.
AB  - INTRODUCTION: Myoepithelial tumours are rare clinicopathological identity. It has
      been found in parotid glands and salivary glands but never reported in
      infratemporal fossa or other sites of lateral skull base region. DISCUSSION:
      Unlike its benign counterpart, myoepithelial carcinoma is biologically very
      aggressive and prone to recur even after adequate therapy. CASE REPORT: Here, a
      rare case of myoepithelial carcinoma arising from infratemporal fossa has been
      described along with its treatment options and outcome.

PMID- 19184134
TI  - Migration of tip knife blade through middle-third facial tissues.
AB  - PURPOSE: The aim of this paper is to report a case of knife aggression with a
      spontaneous migration of a tip blade lodged in deep tissues 6 months after
      trauma. PATIENT: An 18-year-old woman that was a victim of impalement injury with
      a knife by her boyfriend on the glabella region with a blade fracture and tip
      lodging into middle-third facial tissues. RESULTS: After conservative management
      of a knife tip, a spontaneous migration occurred with its exposition on the
      zygomatic area, possibly due to a functional treatment to improve mouth opening.
      CONCLUSION: Fracture of knife blade with a tip retained deeply into the tissues
      is considered foreign body, and its removal must be considered. Nevertheless, the
      basis for this removal takes account the cost-benefit ratio, and if a
      conservative management was chosen, the clinical and radiological accompanying is
      mandatory to prevent and to treat its possible complications.

PMID- 19184135
TI  - Interaction of the SPG21 protein ACP33/maspardin with the aldehyde dehydrogenase
      ALDH16A1.
AB  - Mast syndrome (SPG21) is an autosomal-recessive complicated form of hereditary
      spastic paraplegia characterized by dementia, thin corpus callosum, white matter
      abnormalities, and cerebellar and extrapyramidal signs in addition to spastic
      paraparesis. A nucleotide insertion resulting in premature truncation of the
      SPG21 gene product acidic cluster protein 33 (ACP33)/maspardin underlies this
      disorder, likely causing loss of protein function. However, little is known about
      the function of maspardin. Here, we report that maspardin localizes prominently
      to cytoplasm as well as to membranes, possibly at trans-Golgi network/late
      endosomal compartments. Immunoprecipitation of maspardin with identification of
      coprecipitating proteins by mass spectrometry revealed the aldehyde dehydrogenase
      ALDH16A1 as an interacting protein. This interaction was confirmed using
      overexpressed proteins as well as by fusion protein pull down experiments, and
      these proteins colocalized in cells. Further studies of the function of ALDH16A1
      and the role of the maspardin-ALDH16A1 interaction in neuronal cells may clarify
      the cellular pathogenesis of Mast syndrome.

PMID- 19184137
TI  - Local rather than global processing of visual arrays in numerosity discrimination
      by pigeons (Columba livia).
AB  - A series of experiments investigated which stimulus properties pigeons use when
      they discriminate pairs of visual arrays that differ in numerosity. Transfer
      tests with novel stimuli confirmed that the birds' choices were based on relative
      differences in numerosity. However, pigeons differed from other species in the
      non-numerical cues that affected their choices. In human and non-human primates,
      numerical discrimination is often influenced by continuous variables such as
      surface area or overall stimulus brightness. Pigeons showed little evidence of
      using those cues, even when summed area and brightness had been correlated with
      numerosity differences and reward outcome. But when array-element sizes were
      asymmetrically distributed across numerosities, the birds readily utilized
      information about item sizes as an additional discriminative cue. These novel
      results are discussed in relation to pigeons' tendency to focus on local, rather
      than global dimensions when they process other non-numerical complex visual
      stimuli. The findings suggest there may be inter-specific differences in the type
      of perceptual information that provides the input stage for mechanisms underlying
      numerical processing.

PMID- 19184136
TI  - Examination of association of genes in the serotonin system to autism.
AB  - Autism is characterized as one of the pervasive developmental disorders, a
      spectrum of often severe behavioral and cognitive disturbances of early
      development. The high heritability of autism has driven multiple efforts to
      identify genetic variation that increases autism susceptibility. Numerous studies
      have suggested that variation in peripheral and central metabolism of serotonin
      (5-hydroxytryptamine) may play a role in the pathophysiology of autism. We
      screened 403 autism families for 45 single nucleotide polymorphisms in ten
      serotonin pathway candidate genes. Although genome-wide linkage scans in autism
      have provided support for linkage to various loci located within the serotonin
      pathway, our study does not provide strong evidence for linkage to any specific
      gene within the pathway. The most significant association (p = 0.0002; p = 0.02
      after correcting for multiple comparisons) was found at rs1150220 (HTR3A) located
      on chromosome 11 ( approximately 113 Mb). To test specifically for multilocus
      effects, multifactor dimensionality reduction was employed, and a significant two
      way interaction (p value = 0.01) was found between rs10830962, near MTNR1B
      (chromosome11; 92,338,075 bp), and rs1007631, near SLC7A5 (chromosome16;
      86,413,596 bp). These data suggest that variation within genes on the serotonin
      pathway, particularly HTR3A, may have modest effects on autism risk.

PMID- 19184138
TI  - Does inequity aversion depend on a frustration effect? A test with capuchin
      monkeys (Cebus apella).
AB  - Brosnan and de Waal (Nature 425:297-299, 2003) reported that if a witness monkey
      saw a model monkey receive a high-value food, the witness was more inclined to
      reject a previously acceptable, but low-value food. Later work demonstrated that
      this alleged inequity aversion might be due to frustration induced by switching
      subjects from their role as models receiving a high-value food to the role of
      witnesses receiving a low-value food. In the present study, pairs of female
      capuchins exchanged a token for either a high- or a low-value food without
      switching their model-witness roles. Witnesses could exchange a token for a low
      value food after an adjacent model had exchanged a token for the same food
      (Equity Condition) or for a high-value food (Inequity Condition). Failure- and
      latency-to-exchange measures showed that witnesses were unaffected by the food
      type offered to models (no inequity aversion). Moreover, models were unaffected
      by their history of food type offered (no frustration). These results join
      earlier work suggesting that alleged inequity effects depend on frustration
      induction procedures. Furthermore, inequity effects sometimes fail to emerge
      because frustration induction in nonhuman primates is labile.

PMID- 19184139
TI  - Assessment of high-level gentamicin and glycopeptide-resistant Enterococcus
      faecalis and E. faecium clonal structure in a Portuguese hospital over a 3-year
      period.
AB  - This study focussed on the clonal structure and temporal distribution of E.
      faecalis and E. faecium with high-level resistance to gentamicin (HLGR) and
      glycopeptides (GR) collected from clinical samples during 2004 to 2006 at a
      Portuguese Hospital. The findings were an E. faecalis-dominant and epidemic clone
      (PFGE-AO), the maintenance of a major epidemic E. faecium clone (PFGE-c) and a
      high prevalence of putative virulence genes--asa1 (aggregation substances), gelE
      (gelatinase), cylA (cytolysin), esp (enterococcal surface protein), and hyl
      (hyaluronidase)--most of them significantly associated with the major clones of
      both species. The E. faecalis GR isolates ST6 and the E. faecium GR isolates
      ST17, ST18 and ST280 belong to the clonal complexes E. faecalis-CC2 and E.
      faecium-CC17, which are well adapted to the nosocomial setting and are
      disseminated worldwide. This study highlights the need for continuous and active
      surveillance in this Portuguese hospital in order to follow the evolution of
      these epidemic and persistent clones.

PMID- 19184140
TI  - In vitro and in vivo efficacies of amlodipine against Listeria monocytogenes.
AB  - Listeria monocytogenes causes suppurative gastritis in BALB/c mice. We
      investigated the effect of the antihypertensive drug amlodipine (Aml) on the
      growth of L. monocytogenes in vitro and in vivo. Aml showed noteworthy inhibitory
      action (minimum inhibitory concentration, MIC(90) 32 microg/ml) against Listeria
      strains and demonstrated cidal (minimum bactericidal concentration, MBC 64
      microg/ml) activity. Aml administered orally at 2.5 microg/g in female BALB/c
      mice for 7 days, commencing 4 days before oral challenge (1 x 10(8) CFU/ml with
      L. monocytogenes ATCC 51774), significantly reduced bacterial counts in the
      stomach (P < 0.01), liver (P < 0.01), and spleen (P < 0.05), and decreased (P <
      0.05) gastric lesions, neutrophilic infiltration, edema, vascular degeneration,
      and necrosis of gastric tissues. It caused the down-regulation of expression of
      inflammatory cytokines (IFN-gamma, IL-1 beta, and TNF-alpha) compared to drug
      free control. Aml may be used in the presence of an antibiotic as adjunct therapy
      that boosts the host immunity against Listeria. Further, QSAR studies might
      contribute in manipulating it as a lead compound for the synthesis of new, more
      effective non-antibiotics (helper compounds), perhaps devoid of side-effects,
      that could be recommended as compassionate therapy for listeriosis.

PMID- 19184141
TI  - Daptomycin resistance and treatment failure following vancomycin for methicillin
      resistant Staphylococcus aureus (MRSA) mitral valve acute bacterial endocarditis
      (ABE).
AB  - Acute bacterial endocarditis (ABE) is most commonly due to virulent pathogens,
      i.e., Staphylococcus aureus. S. aureus ABE may be due to methicillin-sensitive
      (MSSA) or methicillin-resistant (MRSA) strains and, optimally, ABE should be
      treated with bactericidal antibiotics. Traditionally, vancomycin has long been
      used to treat MRSA ABE, but it has been shown that vancomycin may increase the
      staphylococcal the thickness, resulting in permeability-mediated resistance. We
      present a case of a 72-year-old male with mitral valve MRSA ABE refractory to
      daptomycin therapy following initial therapy with vancomycin. We were not able to
      diminish the intensity of the patient's MRSA bacteremia from his mitral valve
      ABE, even with high-dose (12 mg/kg day) daptomycin, presumably because of
      permeability-mediated resistance due to antecedent vancomycin therapy.

PMID- 19184143
TI  - Subcutaneous emphysema: diagnostic clue in the emergency room.
AB  - The objective of this study was to illustrate the wide spectrum of subcutaneous
      emphysema in the emergency room; to show the key findings on computed tomography,
      plain radiographs, and echography; and to discuss the differential diagnoses.
      Subcutaneous emphysema is a common finding in emergency department imaging
      studies. It has a great importance due to its broad casualty, some of them
      totally benign, but others potentially lethal. We retrospectively reviewed our
      database of emergency pathology, analyzing its origins and associated features.
      SE was associated to traumatic, iatrogenic, or infectious causes (necrotizing
      fasciitis, Fournier gangrene). It also was found associated with thoracic
      (causing pneumothorax and pneumomediastinum) and abdominal pathology related to
      intraperitoneal and retroperitoneal gas. Diagnostic difficulties and differential
      diagnoses are emphasized. Radiologists must be aware of abnormal gas in soft
      tissue because it may be the main or unique sign leading to an underlying
      pathology, which can be lethal.

PMID- 19184142
TI  - The DePICTORS Study: discrepancies in preliminary interpretation of CT scans
      between on-call residents and staff.
AB  - At many academic hospitals, radiology residents provide preliminary
      interpretations of CT studies performed outside of regular working hours. We
      examined the rate of discrepancies between resident interpretations and final
      reports issued by staff. We prospectively obtained 1,756 preliminary reports and
      corresponding final reports for computed tomography (CT) scans performed on call
      between November 2006 and March 2007. The overall rate of clinically significant
      discrepancies (those that would potentially alter the patient's clinical course
      prior to issue of the final report) was 2.0%. Major discrepancy rates for
      abdominal/pelvic, chest, cervical spine and head CT were 4.1%, 2.5%, 1.0% and
      0.7%, respectively. Senior residents had fewer major discrepancies compared to
      their junior colleagues. Time of interpretation was also evaluated, but a
      statistically significant relationship was not observed. In summary, this study
      demonstrates a low discrepancy rate between residents and staff radiologists and
      identifies areas where after-hours service may be further improved.

PMID- 19184144
TI  - Small-bowel internal herniation through the falciform ligament: 64-row MDCT
      diagnosis.
AB  - We report a very rare case of internal hernia of the small bowel through a large
      congenital defect of the falciform ligament. A complete preoperative diagnosis
      was possible by 64-row multi-detector row computerized tomography. The
      identification of the characteristic anatomic features and landmarks of the
      obliterated umbilical vein-ligamentum teres-was the diagnostic key.

PMID- 19184145
TI  - Spontaneous spinal subarachnoid hemorrhage associated with subdural hematoma at
      different spinal levels.
AB  - We describe the clinical features and MR-imaging findings of spontaneous spinal
      subarachnoid hemorrhage located in the lumbar spine associated with subdural
      hematoma at a higher, thoracic level in a 66-year-old man without neurological
      deficit. The sequential MR-imaging changes of hemorrhage at various stages in its
      evolution are portrayed. The possible pathogenetic mechanism for these very
      unusual, combined hemorrhages in both spinal compartments is discussed.

PMID- 19184146
TI  - Novel genes related to nodulation, secretion systems, and surface structures
      revealed by a genome draft of Rhizobium tropici strain PRF 81.
AB  - Rhizobium tropici is representative of the diversity of tropical rhizobia,
      besides comprising strains very effective in fixing N(2) in symbiosis with the
      common bean (Phaseolus vulgaris L.). The genome of a Brazilian commercial
      inoculant R. tropici strain (PRF 81, =SEMIA 4088), estimated at 7.85 Mb, was
      analyzed through a total of 9,026 shotgun reads, assembled in 1,668 phrap
      contigs, and covering approximately 30% of the genome. Annotation identified
      2,135 coding DNA sequences (CDS), and only 57.2% have possible functions. The
      genome comprises a mosaic of genes, with CDS showing the highest similarities
      with 134 microorganisms, none of which represents more than 19% of the CDS with
      putative known functions. The high saprophytic capacity of PRF 81 may reside in a
      variety of genes related to transport, biodegradation of xenobiotics, defense,
      and secretion proteins, many of which were reported for the first time in the
      present study. Novelty was also found in nodulation (nodG, a double nodIJ system,
      nodT, nolF, nolG) and capsular polysaccharide genes, showing stronger
      similarities with Sinorhizobium (=Ensifer) than with the main symbionts of the
      common bean -- R. etli and R. leguminosarum -- suggesting that the original host
      of R. tropici might be another tropical legume or emphasizing the highly
      promiscuous nature of this rhizobial species.

PMID- 19184147
TI  - Extracranial radiosurgery--applications in the management of benign intradural
      spinal neoplasms.
AB  - Stereotactic radiosurgery has enabled the delivery of higher doses of radiation
      and decreased fractionation due to improved accuracy. Spinal radiosurgery has
      been increasingly utilized for the management of metastatic extradural spinal
      disease. However, surgical resection remains the primary treatment strategy for
      intradural spinal tumors. Preliminary evidence suggests that radiosurgical
      ablation with stereotactic radiation for intradural spinal lesions may be
      efficacious in certain clinical scenarios. Local tumor control, pain relief, and
      improvement in neurologic function with minimal morbidity have been reported in
      short-term follow-up. However, long-term efficacy of radiosurgery in the
      management of intradural spinal neoplasms necessitates further validation. As
      extracranial radiosurgery is a newly evolving modality, a continuative review of
      the current literature is appropriate. Until a standardized therapeutic window of
      safety and efficacy can be determined, the recommendation of radiosurgical
      applications for benign spinal tumors should be reserved for carefully selected
      cases.

PMID- 19184148
TI  - Comparative distribution of a putative egg-laying hormone in neural and
      reproductive tissues of four Decapoda crustaceans.
AB  - Evidence for the presence of a putative egg-laying (ELH) hormone has been
      previously described in the black tiger shrimp, Penaeus monodon, so a further
      investigation was carried out to detect its presence in a range of Decapoda
      crustaceans prior to a full molecular analysis. The crustaceans were represented
      by the Australian fresh water yabbie, Cherax destructor, the Australian southern
      rock lobster, Jasus edwardsii, the snow crab, Chionoecetes opilio, and the blue
      swimmer crab, Portunus pelagicus. Female cerebral ganglia, ventral nerve cords
      and gonads were investigated in a comparative study of the distribution of the
      immunoreactive hormone using immunoenzyme and immunofluorescence techniques.
      Immunoreactivity was detected in all tissues of interest, and the distribution
      patterns showed similarity within the four species, as well as that of P. monodon
      reported in the earlier study. There were minor variations. These data indicate
      that a putative ELH-like neuropeptide is widespread in crustaceans, and supports
      its previous identification in a range of molluscs and other invertebrates.
      Elucidation of the molecular structure of the peptide hormone and its encoding
      gene, as well as its involvement in spawning behaviour of crustaceans, is now
      fully under investigation.

PMID- 19184151
TI  - Shape memory effect of thermoplastic segmented polyurethanes with self
      complementary quadruple hydrogen bonding in soft segments.
AB  - This paper describes the fact that a kind of thermoplastic shape memory
      polyurethane with self-complementary quadruple hydrogen bonding units in soft
      segments can present a significant shape memory effect under the usually used
      thermodynamic programming condition. Compared with the control sample, it was
      observed that the introduction of self-complementary quadruple hydrogen bonding
      into soft segments increases the glass transition temperature from 28.3 degrees C
      to 73.3 degrees C. Therefore, the temporary deformation can be fixed well after
      cooling at room temperature; subsequently thermal responsive shape memory
      recovery can be triggered by heating up to 86 degrees C. The immediate shape
      recovery ratio and shape fixity ratio can be 95.8% and 95.9%. Even after 24 hours
      relaxation for the stretched films, the corresponding R(r) and R(f) can be 94%
      and 60%. In contrast, the sample without quadruple hydrogen bonding shows that
      the elasticity and the deformation cannot be fixed after 24 hours relaxation.

PMID- 19184149
TI  - Electrostatic and electrokinetic contributions to the elastic moduli of a driven
      membrane.
AB  - We discuss the electrostatic contribution to the elastic moduli of a cell or
      artificial membrane placed in an electrolyte and driven by a DC electric field.
      The field drives ion currents across the membrane, through specific channels,
      pumps or natural pores. In steady state, charges accumulate in the Debye layers
      close to the membrane, modifying the membrane elastic moduli. We first study a
      model of a membrane of zero thickness, later generalizing this treatment to allow
      for a finite thickness and finite dielectric constant. Our results clarify and
      extend the results presented by D. Lacoste, M. Cosentino Lagomarsino, and J.F.
      Joanny (EPL 77, 18006 (2007)), by providing a physical explanation for a
      destabilizing term proportional to [see formula in text] in the fluctuation
      spectrum, which we relate to a nonlinear (E(2)) electrokinetic effect called
      induced-charge electro-osmosis (ICEO). Recent studies of ICEO have focused on
      electrodes and polarizable particles, where an applied bulk field is perturbed by
      capacitive charging of the double layer and drives the flow along the field axis
      toward surface protrusions; in contrast, we predict "reverse" ICEO flows around
      driven membranes, due to curvature-induced tangential fields within a
      nonequilibrium double layer, which hydrodynamically enhance protrusions. We also
      consider the effect of incorporating the dynamics of a spatially dependent
      concentration field for the ion channels.

PMID- 19184152
TI  - MRI of human hair.
AB  - INTRODUCTION: Hair care for humans is a major world industry with specialised
      tools, chemicals and techniques. Studying the effect of hair care products has
      become a considerable field of research, and besides mechanical and optical
      testing numerous advanced analytical techniques have been employed in this area.
      In the present work, another means of studying the properties of hair is added by
      demonstrating the feasibility of magnetic resonance imaging (MRI) of the human
      hair. MATERIALS AND METHODS: Established dedicated nuclear magnetic resonance
      microscopy hardware (solenoidal radiofrequency microcoils and planar field
      gradients) and methods (constant time imaging) were adapted to the specific needs
      of hair MRI. RESULTS: Images were produced at a spatial resolution high enough to
      resolve the inner structure of the hair, showing contrast between cortex and
      medulla. Quantitative evaluation of a scan series with different echo times
      provided a T*(2) value of 2.6 ms for the cortex and a water content of about 90%
      for hairs saturated with water. CONCLUSION: The demonstration of the feasibility
      of hair MRI potentially adds a new tool to the large variety of analytical
      methods used nowadays in the development of hair care products.

PMID- 19184154
TI  - The augmented RIC model of the human respiratory system.
AB  - This paper describes the augmented RIC model of respiratory impedance and
      analyzes its parameter values estimated--by a modified Newton method with least
      squares criterion--from impulse oscillometry data. The data were from asthmatic
      children, tested pre- and post-bronchodilator, and from healthy adults and a
      second group of adults with COPD. Our analyses show that the augmented RIC model
      was 13.7-66.6% more accurate than the extended RIC model at fitting these data,
      while its parameter estimates were within previously reported ranges, unlike the
      Mead 1969, DuBois and Mead models, which typically yielded compliance estimates
      exceeding 200 l/kPa. Additionally, the augmented RIC model's C(p) parameter,
      representing peripheral airway compliance, is a statistically significant
      discriminator between unconstricted and constricted conditions (with p < 0.001)
      occurring in asthma and COPD. This corresponds well with current medical
      understanding, so the augmented RIC model is potentially useful for detection and
      treatment of airflow obstruction.

PMID- 19184153
TI  - Transitions of multifocal electroretinography following combined intravitreal
      bevacizumab and photodynamic therapy for polypoidal choroidal vasculopathy.
AB  - To investigate the changes in the multifocal electroretinography (ERG) after
      combined intravitreal bevacizumab and photodynamic therapy (PDT) for polypoidal
      choroidal vasculopathy (PCV) patients. Thirteen eyes of 13 patients were included
      in the study. The latencies and average response densities of all the six ring
      retinal regions were measured and compared before treatment and 1, 3, and 6
      months after treatment. The latencies of the N1 and P1 waves in all the six rings
      remained unchanged compared with pre-treatment. Significant increase of average
      response densities of both P1 in ring 1 (P = 0.023) and N1, P1 in ring 2 (P =
      0.028 and 0.046, respectively) were detected at 3 months post-treatment. The
      increase of P1 amplitude densities in ring 1 (P = 0.015) and N1, P1 amplitude
      densities in ring 2 (P = 0.031 and 0.034, respectively) were also significant at
      6 months post-treatment. In conclusion, combined intravitreal bevacizumab and PDT
      is associated with an increase of multifocal ERG centrally in PCV patients.

PMID- 19184156
TI  - Improving backdrivability in geared rehabilitation robots.
AB  - Many rehabilitation robots use electric motors with gears. The backdrivability of
      geared drives is poor due to friction. While it is common practice to use
      velocity measurements to compensate for kinetic friction, breakaway friction
      usually cannot be compensated for without the use of an additional force sensor
      that directly measures the interaction force between the human and the robot.
      Therefore, in robots without force sensors, subjects must overcome a large
      breakaway torque to initiate user-driven movements, which are important for motor
      learning. In this technical note, a new methodology to compensate for both
      kinetic and breakaway friction is presented. The basic strategy is to take
      advantage of the fact that, for rehabilitation exercises, the direction of the
      desired motion is often known. By applying the new method to three implementation
      examples, including drives with gear reduction ratios 100-435, the peak breakaway
      torque could be reduced by 60-80%.

PMID- 19184157
TI  - Applying fractal analysis to short sets of heart rate variability data.
AB  - The aim of this study was to explore the interchangeability of fractal scaling
      exponents derived from short- and long-term recordings of real and synthetic
      data. We compared the alpha(1) exponents as obtained by detrended fluctuation
      analysis from RR-interval series (9 am to 6 pm) of 54 adults in normal sinus
      rhythm, and the alpha(1) estimated from shorted segments of these series
      involving only 50, 100, 200 and 300 RR intervals. Three series of synthetic data
      were also analysed. The principal finding of this study is the lack of individual
      agreement between alpha(1) derived from long and short segments of HRV data as
      indicated by the existence of bias and low intraclass correlation coefficient
      (r(i) = 0.158). The extent of variation in the estimation of alpha(1) from real
      data does not only appear related to segments' length, but also to different
      dynamics among subjects or lack of uniform scaling behaviour. However, we did
      find statistical agreement between the means of alpha(1) exponents from long and
      short segments, even for segments involving just 50 RR intervals. According to
      results of synthetic series, the 95% confidence interval found for the variation
      of alpha(1) using segments with 300 samples is [-0.1783 + 0.1828]. Caution should
      be taken concerning the use of short segments to obtain representative exponents
      of fractal RR dynamics; a circumstance not fully considered in several studies.

PMID- 19184158
TI  - Unsupervised classification of atrial heartbeats using a prematurity index and
      wave morphology features.
AB  - ECG heartbeat type detection and classification are regarded as important
      procedures since they can significantly help to provide an accurate automated
      diagnosis. This paper addresses the specific problem of detecting atrial
      premature beats, that had been demonstrated to be a marker for stroke risk or
      cardiac arrhythmias. The proposed methodology consists of a stage to estimate
      characteristics such as morphology of P wave and QRS complex as well as indices
      of prematurity and a non-supervised stage used by the algorithm J-means to
      separate heartbeat feature vectors into classes. Partition initialization is
      carried out by a Max-Min approach. Experimental data set is taken from MIT-BIH
      arrhythmia database. Results evidence the reliability of the method since
      achieved sensitivity and specificity are high, 92.9 and 99.6%, respectively, for
      an average output number of 12 discovered clusters that can be considered as
      appropriate value to separate heartbeat classes from recordings.

PMID- 19184159
TI  - Modeling the macro-structure of the heart: healthy and diseased.
AB  - In a common heart pathology, dilated cardiomyopathy, the ventricular chamber
      undergoes a complex remodeling that changes the shape of the ventricle and the
      architecture of the fibers in the myocardium. In order to effectively surgically
      reconstruct the heart it is necessary to understand the relative impact of these
      changes on heart function. Here we present a series of simulations that model
      different pathological changes separately. We use the sensitive relationship
      between twist of the ventricle and its ejection fraction to judge the functional
      impact of the different damage types. We show that the anomalies found in the
      relation between torsion and ejection fraction for dilated cardiomyopathy are
      predominantly caused by the damage to the architecture of the myofibrils of the
      heart, rather than gross geometry.

PMID- 19184160
TI  - Structures of the ceramides from porcine palatal stratum corneum.
AB  - Ceramides are the major type of lipid found in stratum corneum from the skin,
      gingiva and hard palate. The present study examined the ceramides of the stratum
      corneum from the hard palate. Six fractions of ceramides were isolated by
      preparative thin-layer chromatography. The least polar fraction contained an
      unusual acyl ceramide (EOS) consisting of long omega-hydroxy acids amide-linked
      to sphingosine with mostly saturated fatty acids ester-linked to the omega
      hydroxyl group. The second and third fractions contained normal fatty acids amide
      linked to sphingosine (NS) and phytosphingosine (NP), respectively. In each of
      these ceramides, the fatty acids consisted of a mixture of saturated and
      monoenoic species. The three most polar fractions all contain amide-linked alpha
      hydroxy acids. The fourth fraction contained long alpha-hydroxy acids amide
      linked to sphingosine (ASl), while the fifth fraction contained short alpha
      hydroxy acids amide-linked to sphingosine (ASs). The most polar ceramide
      contained alpha-hydroxy acids amide-linked to phytosphingosine (AP). EOS, NS and
      NP differed from their epidermal counterparts in terms of the compositions of the
      normal fatty acids. ASl, ASs and AP from palatal stratum corneum were essentially
      identical to their epidermal counterparts. The differences between palatal and
      epidermal EOS, NS and NP contribute to the differences in permeability of palate
      compared to skin.

PMID- 19184161
TI  - Evaluating the trans fatty acid, CLA, PUFA and erucic acid diversity in human
      milk from five regions in China.
AB  - Human milk was obtained from 97 healthy lactating women from five different
      regions in China. Twenty-four hour dietary questionnaire identified the foods
      consumed that showed distinct differences in food types between cities. The
      southern and central regions had higher levels of total trans fatty acids (TFA)
      and conjugated linoleic acids (CLA) in human milk than the northern region. The
      major isomers in human milk from the northern region were vaccenic and rumenic
      acids, whereas the other regions had a random distribution of these isomers. This
      was consistent with the isomer distribution in the refined vegetable oils used
      and their increased formation during high temperature stir-frying. The human milk
      composition showed little evidence that partially hydrogenated fats were
      consumed, except eight mothers in Guangzhou who reported eating crackers, plus
      four other mothers. The TFA concentration in these human milk samples was higher
      (2.06-3.96%). The amount of n-6 (1.70-2.24%) and n-3 (0.60-1.47%) highly
      unsaturated fatty acids (HUFA) in human milk and the resultant ratio (1.43-2.95)
      showed all mothers in China had an adequate supply of HUFA in their diet.
      Rapeseed oil was consumed evidenced by erucic acids in human milk. The levels of
      erucic acid were below internationally accepted limits for human consumption. The
      levels of undesirable TFA and CLA isomers in human milk are a concern. Efforts to
      decrease the practice of high temperature stir-frying using unsaturated oils, and
      a promotion to increase consumption of dairy and ruminant products should be
      considered in China.

PMID- 19184163
TI  - Obstetric complications as a risk factor for first psychotic episodes in
      childhood and adolescence.
AB  - There are reports of significant association between obstetric complications (OC)
      and childhood psychosis. Authors conducted a case-control study of 102 children
      and adolescents with a first episode psychosis (FEP) and 94 healthy controls
      (HC), using the obstetric complications scale (OCS) and their medical records, to
      examine the risk of FPE. Patients were recruited from child and adolescent
      psychiatry units at six university hospitals and controls from publicly-funded
      schools of similar characteristics and from the same geographic areas. A logistic
      regression was performed to quantify the risk of psychosis in childhood and
      adolescence, based on OC, adjusting for potential confounding factors like socio
      economic status (SES) and family psychiatric history (FPH). OC appeared more
      frequently in the records of patients. Significant differences between patients
      and controls were found in Prenatal OC (15.7% vs. 5.3%, P < 0.05) and among them,
      bleeding in pregnancy showed the greatest difference between groups (12.7% vs.
      2.1%, P < 0.01). In the logistic regression, bleeding in pregnancy showed a crude
      odds ratio (OR) of 6.7 (95%CI = 1.4-30.6) and 5.1 (CI 95% = 1.0-24.9) adjusted
      for SES and FPH. Therefore, bleeding in pregnancy is a likely risk factor for
      early-onset psychosis.

PMID- 19184162
TI  - MDR1 variants and risk of Parkinson disease. Association with pesticide exposure?
AB  - The multidrug resistance protein 1 (MDR1 or ABCB1) gene encodes a P-glycoprotein
      that protects the brain against neurotoxicants. Certain MDR1 genetic variants are
      known to compromise the function of this transporter and may thus be associated
      with Parkinson disease (PD). We therefore conducted a large case-control study
      investigating the potential relationship between MDR1 variants and PD. We
      determined the frequency of three MDR1 variants in 599 European PD patients and
      controls and further stratified the population by ethnicity, age at onset, and
      exposure to pesticides. We detected no relevant association in either the entire
      sample, or when separately investigating by ethnic origin or age at onset.
      However, the distribution of c.3435C/T differed significantly between PD patients
      exposed to pesticides compared to those non-exposed (odds ratio=4.74; confidence
      interval=[1.009; 22.306]); p=0.047), suggesting that common MDR1 variants might
      influence the risk to develop PD in conjunction with exposure to pesticides.

PMID- 19184164
TI  - Evidence for nonindependent evolution of adjacent microsatellites in the human
      genome.
AB  - Microsatellites are short tandem repeats that evolve predominantly through a
      stepwise mutation model. Despite intensive study, many aspects of their evolution
      remain unresolved, particularly the question of how compound microsatellites
      containing two different motifs evolve. Previous work described profound
      asymmetries in the probability that any given second motif lies either 3' or 5'
      of an AC repeat tract. Here we confirm and extend this analysis to examine the
      length dependence of these asymmetries. We then use the differences in length
      between homologous human and chimpanzee microsatellites as a surrogate measure of
      the slippage-based mutation rate to explore factors that influence this process.
      We find that the dominant predictor of mutation rate is the length of the tract
      being considered, which is a stronger predictor than the length of the two tracts
      combined, but other factors also have a significant impact, including the length
      of the second tract and which of the two tracts lies upstream. We conclude that
      compound microsatellites rarely arise through random point mutations generating a
      second motif within a previously pure tract. Instead, our analyses point toward a
      model in which poorly understood mutation biases, probably affecting both
      slippage and point mutations and often showing 3'-5' polarity, promote the
      formation of compound microsatellites. The result is convergent evolution. We
      suggest that, although their exact nature remains unclear, these biases are
      likely attributable to structural features, such as the propensity of AC tracts
      to form Z-DNA.

PMID- 19184165
TI  - Snake population venomics: proteomics-based analyses of individual variation
      reveals significant gene regulation effects on venom protein expression in
      Sistrurus rattlesnakes.
AB  - Studies of the molecular basis of adaptations seek to understand the relative
      importance of structural changes in proteins versus gene regulation effects as
      determinants of phenotype. Amino acid substitutions in gene coding sequences are
      well documented as causes of variation in snake venom proteins, whereas the
      importance of gene regulation effects on venom protein abundance and composition
      is less well known. Here, we use a proteomics-based approach to infer the effects
      of gene regulation on protein expression by comparing the relative abundance of
      specific, known venom proteins among different individuals in each of two species
      of Sistrurus rattlesnakes. Variation in the presence or absence, and in the
      relative amounts, of proteins was high in both species across all major protein
      families. Based on our empirical criteria for inferring regulatory effects
      (presence-absence of specific proteins and/or more than threefold variation in
      abundance) between 51% and 83% of S. catenatus individuals and between 40% and
      63% of S. miliarius individuals showed evidence for gene regulation across the
      four most abundant proteins (disintegrins, phospholipase A(2)'s, serine
      proteinases, and snake venom metalloproteases). Thus, the effects of gene
      regulation should be considered an important cause of variation in the
      composition of whole venoms at the intraspecific level. They also suggest the
      need for testing the adaptive hypothesis for venom plasticity in relation to prey
      consumed by adult snakes. Finally, the venom variability reported may have an
      impact in the treatment of bite victims, highlighting the necessity of using
      pooled venoms as a substrate for antivenom production.

PMID- 19184166
TI  - Use of sugar cane vinasse to mitigate aluminum toxicity to Saccharomyces
      cerevisiae.
AB  - Owing to its toxicity, aluminum (Al), which is one of the most abundant metals,
      inhibits the productivity of many cultures and affects the microbial metabolism.
      The aim of this work was to investigate the capacity of sugar cane vinasse to
      mitigate the adverse effects of Al on cell growth, viability, and budding, as the
      likely result of possible chelating action. For this purpose, Fleischmann's yeast
      (Saccharomyces cerevisiae) was used in growth tests performed in 125-mL
      Erlenmeyer flasks containing 30 mL of YED medium (5.0 g/L yeast extract plus 20
      g/L glucose) supplemented with the selected amounts of either vinasse or Al in
      the form of AlCl(3) . H(2)O. Without vinasse, the addition of increasing levels
      of Al up to 54 mg/L reduced the specific growth rate by 18%, whereas no
      significant reduction was observed in its presence. The toxic effect of Al on S.
      cerevisiae growth and the mitigating effect of sugar cane vinasse were quantified
      by the exponential model of Ciftci et al. (Biotechnol Bioeng 25:2007-2023, 1983).
      The cell viability decreased from 97.7% at the start to 84.0% at the end of runs
      without vinasse and to 92.3% with vinasse. On the other hand, the cell budding
      increased from 7.62% at the start to 8.84% at the end of runs without vinasse and
      to 17.8% with vinasse. These results demonstrate the ability of this raw material
      to stimulate cell growth and mitigate the toxic effect of Al.

PMID- 19184167
TI  - Propagating knowledge: the value of the single center experience.

PMID- 19184168
TI  - Severity scoring system for ventricular septal defect.

PMID- 19184169
TI  - Is left ventricular noncompaction in children truly an isolated lesion?
AB  - Left ventricular noncompaction (LVNC) is a form of cardiomyopathy resulting from
      a disorder of endomyocardial morphogenesis. It has been associated with
      significant morbidity and mortality. The aim of this study was to characterize
      associated cardiac findings in children with LVNC and to identify risk factors
      associated with increased mortality. From our echocardiography database, we
      identified 46 patients diagnosed with LVNC between December 1999 and February
      2005. The mean age at presentation was 3.6 +/- 5.6 years, and the mean duration
      of follow-up was 1.9 +/- 2.1 years. Left ventricular ejection fraction was
      decreased in 24 patients (52%; mean 39.5% +/- 13.1%). Thirty-six patients (78%)
      had associated cardiac lesions, including atrial septal defect (n = 16 [35%]),
      ventricular septal defect (n = 17 [37%]), patent ductus arteriosus (n = 14
      [30%]), and Ebstein's anomaly (n = 5 [11%]). Electrocardiogram abnormalities were
      found in 80% of patients; most commonly they included left (n = 15 [43%]) and
      right ventricular hypertrophy (n = 19 [54%]). Documented arrhythmias included
      ectopic atrial rhythm (n = 2), junctional rhythm (n = 2), supraventricular
      tachycardia (n = 2), and ventricular tachycardia (n = 1). Overall mortality was
      20%, and there was no association with ejection fraction, morphologic defect, or
      arrhythmia. Mean age at diagnosis in survivors (4.5 +/- 6.1 years) was higher
      than nonsurvivors (0.4 +/- 0.7 years) (p < 0.0001). LVNC is a rarely isolated
      form of cardiomyopathy, and it is associated with significant additional cardiac
      abnormalities. Although it does not have an invariably fatal course, early
      presentation in infancy does carry an increased risk of mortality.

PMID- 19184170
TI  - The influence of different surgical approaches on arterial rigidity in children
      after aortic coarctation repair.
AB  - Complications, such as recoarctation or secondary hypertension, probably related
      to the loss of arterial elasticity, frequently occur after aortic coarctation
      surgery. This study aimed to investigate arterial compliance as evaluated by
      automated recording of the QKd interval in patients who underwent repair of
      coarctation by construction of a subclavian flap compared with those who
      underwent resection of the narrowed aortic segment with end-to-end anastomosis.
      Thirty-nine children who underwent surgical repair of aortic coarctation by
      subclavian flap (n = 19) and by end-to-end anastomosis (n = 20) were enrolled.
      Arterial stiffness was measured by the noninvasive QKd 100-60 method. Twenty-four
      hour ambulatory blood pressure monitoring and a transthoracic echocardiography
      were also performed. The group of patients who had an end-to-end anastomosis
      showed better results regarding 24-hour blood pressure profile and QKD 100-60
      value compared with those underwent construction of a subclavian flap. Surgical
      repair of aortic obstruction by end-to-end anastomosis demonstrates better
      preservation of arterial distensibility than those repaired by subclavian flap.
      Therefore, it appears to be advantageous, whenever possible, to use the end-end
      anastomosis approach, which appears to lessen the incidence of the most common
      complications after aortic arch surgery.

PMID- 19184171
TI  - Successful epicardial catheter ablation of micro-reentrant ventricular
      tachycardia in a 14-year-old child.
AB  - The article describes successful epicardial catheter ablation of ventricular
      tachycardia using the transpericardial approach in a 14-year-old adolescent.
      Conventional mapping of endocardial surface revealed criteria consistent with
      subpericardial localization of arrythmogenic substrate. Epicardial mapping using
      a transpericardial approach enabled localization and successful elimination of
      the ventricular tachycardia on the lateral wall of the right ventricle.

PMID- 19184172
TI  - Clinical and genetic analysis of long QT syndrome in children from six families
      in Saudi Arabia: are they different?
AB  - Congenital long QT syndrome (LQTS) is an inherited cardiac arrhythmia disorder
      characterized by prolongation of the QT interval; patients are predisposed to
      ventricular tachyarrhythmias and fibrillation leading to recurrent syncope or
      sudden cardiac death. We performed clinical and genetic studies in six Saudi
      Arabian families with a history of sudden unexplained death of children. Clinical
      symptoms, ECG phenotypes, and genetic findings led to the diagnosis of LQT1 in
      two families (recessive) and LQT2 in four families (three recessive and one
      dominant). Onset of arrhythmia was more severe in the recessive carriers and
      occurred during early childhood in all recessive LQT1 patients. Arrhythmia
      originated at the intrauterine stages of life in the recessive LQT2 patients.
      LQT1, causing mutation c.387-5 T > A in the KCNQ1 gene, and LQT2, causing
      mutation c.3208 C > T in the KCNH2 gene, are presumably founder mutations in the
      Assir province of Saudi Arabia. Further, all LQTS causing mutations detected in
      this study are novel and have not been reported in other populations.

PMID- 19184173
TI  - Outcomes for patients with unbalanced atrioventricular septal defects.
AB  - Infants with an unbalanced atrioventricular septal defect (AVSD) frequently
      present with comorbidities that may have an impact on their medical course and
      outcome. This study aimed to assess outcomes and explore possible prognostic
      indicators for patients undergoing surgical palliation for an unbalanced AVSD.
      The medical records of all infants presenting to the authors' institution with an
      unbalanced AVSD over a 5-year period were retrospectively reviewed for assessment
      of outcomes and comorbidities. The study group consisted of 44 patients with an
      overall survival rate of 51% for the entire follow-up period. The majority of
      these patients (88%) underwent single-ventricle palliation, with an 83% rate of
      survival to initial hospital discharge and an overall long-term survival rate of
      50%. The midterm outcome was significantly worse than that for a cohort of
      hypoplastic left heart syndrome patients undergoing single-ventricle palliation
      during the same period (P = 0.03). In addition, 30% of the patients required
      either repair or replacement of their systemic atrioventricular valve at initial
      palliation or during subsequent follow-up evaluation. Of the patients with an
      unbalanced AVSD, 75% had associated congenital anomalies. In conclusion, infants
      with an unbalanced AVSD are a high-risk population with diminished midterm
      survival compared with palliated patients who have more classic forms of
      hypoplastic heart syndromes. This may be due to the higher incidence of both
      severe atrioventricular valve regurgitation and important associated congenital
      anomalies.

PMID- 19184174
TI  - Staff radiation doses in interventional cardiology: correlation with patient
      exposure.
AB  - In pediatric interventional cardiology, cardiologists need to stay closer to the
      patient than during adult catheterization, and the use of biplane systems
      increases the scatter radiation. Occupational radiation risk is rather high, and
      estimation of lens doses becomes necessary. Deriving factors for assessing these
      doses from the patient doses displayed in catheterization laboratories can help
      in preserving staff radiation safety. A biplane X-ray system and
      polymethylmethacrylate plates of 4 to 20 cm to simulate pediatric patients have
      been used. Patient entrance dose rates, dose-area product, and doses to the eyes
      of the cardiologists for the typical operation modes have been measured.
      Correlations between patient and staff doses have been obtained. Scatter dose
      rates increase by a factor of 92 from low fluoroscopy to cine acquisition when
      phantom thickness increases from 4 to 20 cm. Scatter doses increase linearly with
      dose-area product for all the thicknesses. Administration of 1 Gy x cm(2) to the
      patient involves 7 microSv to the eyes of the cardiologist (without extra
      protection). In conclusion, the experimental correlation factors found between
      phantom and scatter doses allow a fairly good estimation of staff doses from the
      dosimetric patient data.

PMID- 19184175
TI  - Serum level of soluble intercellular adhesion molecule-1 correlates with
      pulmonary arterial pressure in children with congenital heart disease.
AB  - BACKGROUND: Endothelial activation and vascular inflammation are thought to be
      the mechanisms of pulmonary hypertension. Increased expression of the
      intercellular adhesion molecule (ICAM-1) and raised serum level of its soluble
      form (sICAM-1) are found in various conditions associated with endothelial
      activation. METHODS: Serum samples from 31 children (14 boys and 17 girls; age,
      4.9 +/- 4.6 years) with congenital heart disease (CHD) collected at the time of
      cardiac catheterization were analyzed for sICAM-1 level. Uni- and multivariable
      stepwise linear regression analyses were performed for the following variables
      against the sICAM-1 level: age, hemoglobin, serum creatinine, systemic arterial
      pressure (SAP), pulmonary arterial pressure (PAP), pulmonary blood flow (Qp) and
      resistance (Rp), systemic blood flow (Qs) and resistance (Rs), Qp/Qs, Rp/Rs, and
      pulmonary and systemic oxygen saturation. RESULTS: The sICAM-1 levels in children
      who had CHD with and without pulmonary hypertension were 411 +/- 110 and 344 +/-
      81 ng/ml, respectively (p = 0.11). In the univariable models, age, serum
      creatinine, systolic PAP, mean PAP, diastolic PAP, Rp, and Rp/Rs were
      significantly correlated with sICAM-1 level. In the multiple stepwise regression
      model, only mean PAP remained as an independent predictor of sICAM-1 level (r =
      0.55; p = 0.002). CONCLUSION: Children with CHD and pulmonary hypertension had a
      trend toward elevated sICAM-1 compared with CHD children who had no pulmonary
      hypertension. A linear correlation was found between mean pulmonary arterial
      pressure and sICAM-1 level.

PMID- 19184176
TI  - Noninvasive evaluation of left ventricular noncompaction: what's new in 2009?
AB  - Significant interest in clinical practice as well as the medical literature
      exists regarding the presentation and outcome of children and adults with left
      ventricular noncompaction (LVNC). The mainstay in the diagnosis of LVNC has been
      the anatomic definition of the ventricular myocardium by two-dimensional
      echocardiographic imaging. Although helpful, this approach lacks diagnostic
      precision and fails to evaluate the functional impact of this abnormal myocardial
      architecture on global and regional myocardial performance. This review will
      focus on the use of novel echocardiographic modalities of tissue Doppler, strain,
      and strain rate imaging to identify and characterize abnormalities of regional
      myocardial function in patients with LVNC.

PMID- 19184177
TI  - Monitoring clonal growth in the developing ventricle.
AB  - Understanding the etiology of congenital heart defects depends on a detailed
      knowledge of the morphogenetic events underlying cardiac development. Deciphering
      the developmental processes and cell behaviors resulting in the formation of a
      four-chambered heart requires techniques by which the destiny of individual cells
      can be traced during development. Ideally, such approaches provide information on
      progenitor cells and growth properties of clonally related myocytes. In the avian
      system, clonal analysis based on the use of replication-defective retroviral
      labeling led to a model for growth of the ventricular wall from polyclonal
      transmural cones of myocardial cells. In the mouse, the nlaacZ retrospective
      clonal analysis system has proved to be a powerful technique for studying
      different aspects of cardiac morphogenesis. Morphologic and histologic analyses
      of clonally related myocytes at early stages of development have provided genetic
      evidence for the formation of the heart tube from two cell lineages. Additional
      aspects of cardiac morphogenesis, including formation of the interventricular
      septum and myocardial outflow tract, and more recently, the origin of the
      ventricular conduction system, have been studied using this system. This brief
      review discusses how the nlaacZ system has provided new insights into the
      divergent properties of clonally related cells in these different regions of the
      developing heart.

PMID- 19184179
TI  - Concepts of cardiac development in retrospect.
AB  - Recent research, enabled by powerful molecular techniques, has revolutionized our
      concepts of cardiac development. It was firmly established that the early heart
      tube gives rise to the left ventricle only, and that the remainder of the
      myocardium is recruited from surrounding mesoderm during subsequent development.
      Also, the cardiac chambers were shown not to be derived from the entire looping
      heart tube, but only from the myocardium at its outer curvatures. Intriguingly,
      many years ago, classic experimental embryological studies reached very similar
      conclusions. However, with the current scientific emphasis on molecular
      mechanisms, old morphological insights became underexposed. Since cardiac
      development occurs in an architecturally complex and dynamic fashion, molecular
      insights can only fully be exploited when placed in a proper morphological
      context. In this communication we present excerpts of important embryological
      studies of the pioneers of experimental cardiac embryology of the previous
      century, to relate insights from the past to current observations.

PMID- 19184178
TI  - Stem cells from in- or outside of the heart: isolation, characterization, and
      potential for myocardial tissue regeneration.
AB  - Heart failure emerges with a net loss of viable cardiomyocytes, and there is no
      current therapy to reverse this process to improve long-term cardiac function.
      Due to a change in viewpoint, that the human heart cannot be considered a
      terminally differentiated postmitotic organ, incapable of myocardial
      regeneration, a belief in a new approach for therapy evolved: regenerating the
      heart. Finding stem cells in the heart capable of replenishing lost
      cardiomyocytes became a holy grail for research. Heart stem cells were isolated
      and characterized, originally derived from in- or outside of the heart. Since the
      endogenous repair potential of the heart following injury is not sufficient,
      cellular therapy has been performed after myocardial infarction in clinical
      settings. Clinical therapies performed with autologous skeletal myoblasts,
      cardiomyocytes, and bone marrow, as well as the animal studies, showed
      improvements in cardiac function, although the clinical effects are still
      limited. These findings have stimulated optimism that progression of heart
      failure might be prevented or even reversed with cell-based therapy. For future
      research, it will be a challenge to isolate the most potent therapeutic cell with
      an intrinsic capacity to stimulate regeneration in the heart, by direct
      participation or by producing paracrine factors.

PMID- 19184180
TI  - Partial anomalous pulmonary venous drainage in young pediatric patients: the role
      of magnetic resonance imaging.
AB  - Studies of larger patient groups for systematic assessment of the anatomical
      accuracy of magnetic resonance imaging (MRI) for partial anomalous pulmonary
      venous drainage (PAPVD) have been performed so far only in adults. This study was
      undertaken to evaluate whether MRI can precisely depict pulmonary venous anatomy
      in infants and young children. Data on 26 children under 10 years old that
      underwent MRI over the past 2 years for suspected PAPVD were assessed. The MRI
      protocol included shunt quantification by velocity-encoded cine as well as
      morphological and functional assessment by multislice multiphase and contrast
      enhanced MR techniques. MRI was performed in the compliant patient in breath-hold
      (n = 8; age range, 4.6-9.5 years) and in the noncompliant patient in conscious
      sedation free breathing (n = 18; age range, 0.4 to 7.5 years). In 22 patients,
      PAPVD was diagnosed with MRI and confirmed during surgery. In four patients with
      large atrial septal defects not accessible to percutaneous closure, normal
      pulmonary venous return was demonstrated by MRI and confirmed during surgery. MRI
      under conscious sedation accurately specifies the anatomy of pulmonary veins in
      infants and small children. Therefore, we suggest performing MRI in patients with
      inconclusive transthoracic echocardiographic results in the preoperative
      assessment of PAPVD.

PMID- 19184182
TI  - Arrhythmia in the neonatal intensive care unit.
AB  - A random sample of 457 neonates was prospectively studied in order to identify
      the incidence, common types, and risk factors for arrhythmias in the neonatal
      intensive care unit (NICU). A 12-lead EKG was studied in all neonates (n = 457).
      A total of 139 Holter studies was done in every fourth baby with a normal EKG (n
      = 100) and in all babies with an abnormal EKG (n = 39). Of the 100 infants who
      were thought to be arrhythmia-free by EKG, nine infants demonstrated an
      arrhythmia on Holter studies. When we correlated screening results with maternal,
      obstetrical, and neonatal risk factors; arrhythmias were significantly associated
      with male gender, more mature gestational age, lower glucose levels, maternal
      smoking, high umbilical artery lines, and the use of the nebulized beta-2
      adrenergic treatment, whereas umbilical venous lines and dopamine infusion did
      not relate to arrhythmia. We conclude that arrhythmias are more common in the
      NICU than in the general neonatal population. Compared to Holter monitoring, the
      sensitivity of the EKG was only 89%.

PMID- 19184181
TI  - Cardiogenetics, neurogenetics, and pathogenetics of left ventricular
      hypertrabeculation/noncompaction.
AB  - BACKGROUND: Left ventricular hypertrabeculation (LVHT), also known as
      noncompaction or spongy myocardium, is a cardiac abnormality of unknown etiology
      and pathogenesis frequently associated with genetic cardiac and noncardiac
      disorders, particularly genetic neuromuscular disease. This study aimed to review
      the current knowledge about the genetic or pathogenetic background of LVHT.
      METHODS: A literature review of all human studies dealing with the association of
      LVHT with genetic cardiac and noncardiac disorders, particularly neuromuscular
      disorders, was conducted. RESULTS: Most frequently, LVHT is associated with
      mitochondrial disorders (mtDNA, nDNA mutations), Barth syndrome (G4.5, TAZ
      mutations), hypertrophic cardiomyopathy (MYH7, ACTC mutations), zaspopathy
      (ZASP/LDB3 mutations), myotonic dystrophy 1 (DMPK mutations), and
      dystrobrevinopathy (DTNA mutations). More rarely, LVHT is associated with
      mutations in the DMD, SCNA5, MYBPC3, FNLA1, PTPN11, LMNA, ZNF9, AMPD1, PMP22,
      TNNT2, fibrillin2, SHP2, MMACHC, LMX1B, HCCS, or NR0B1 genes. Additionally, LVHT
      occurs with a number of chromosomal disorders, polymorphisms, and not yet
      identified genes, as well in a familial context. The broad heterogeneity of
      LVHT's genetic background suggests that the uniform morphology of LVHT not only
      is attributable to embryonic noncompaction but also may result from induction of
      hypertrabeculation as a compensatory reaction of an impaired myocardium.
      CONCLUSIONS: Most frequently, LVHT is associated with mutations in genes causing
      muscle or cardiac disease, or with chromosomal disorders. These associations
      require comprehensive cardiac, neurologic, and cytogenetic investigations.

PMID- 19184183
TI  - Comparison of clinical characteristics and frequency of adverse outcomes in
      patients with Marfan syndrome diagnosed in adulthood versus childhood.
AB  - Patients with Marfan syndrome (MFS) continue to elude diagnosis until well into
      adulthood. The purpose of this study was to compare the clinical characteristics
      and outcomes of adult survivors with MFS diagnosed during adulthood (age, >or=18
      years) with those of adult survivors with MFS diagnosed in childhood (<18 years).
      We conducted a retrospective review of 66 adult (age, >18 years) MFS patients
      seen at a combined pediatric and adult multidisciplinary MFS clinic from 2004 to
      2006. Demographic, clinical, and cardiac variables were collected and a
      comparative analysis was performed between the two groups: patients diagnosed
      with MFS during childhood and patients diagnosed in adulthood. The primary
      outcome measures were the presence of aortic dissection and the need for urgent
      cardiovascular surgery. Despite a similar incidence of clinical characteristics,
      39 of the 66 MFS patients were not diagnosed until adulthood. The overall
      incidence of major cardiac involvement was comparable between the two groups,
      although the patients diagnosed at a younger age were found to have a reduced
      need for aortic surgery (33% vs. 59%; P < 0.04) and fewer adverse cardiac
      outcomes (0% vs. 46%; P < 0.001). Moreover, the patients diagnosed with MFS in
      adulthood were more likely to require repeated surgical intervention for distal
      aortic disease (13% vs. 0%; P = 0.07). In conclusion, patients with MFS who
      remain undiagnosed until adulthood have well-established cardiovascular pathology
      frequently requiring surgical intervention. Due to this delay in diagnosis and
      management, they often suffer from a suboptimal clinical outcome. Our research
      demonstrates the importance of educating pediatric clinicians in early MFS
      diagnosis in hopes of improving the long-term outcome of all MFS patients.

PMID- 19184185
TI  - Dynamics and nutritional ecology of a nanoflagellate preying upon bacteria.
AB  - Ingestion and growth rates of the nanoflagellate predator Ochromonas danica
      feeding on the bacterium Pseudomonas fluorescens were quantified in laboratory
      cultures. Bacterial prey were grown under four nutritional conditions with
      respect to macronutrient elements: C-limited, N-limited, P-limited, and balanced.
      Ingestion and growth rates were saturating functions of prey abundance when
      preying upon nutritionally balanced, C-limited, and P-limited bacteria but were
      unimodal functions of abundance when preying on N-limited bacteria. At saturating
      prey concentrations, the ingestion rate of C-limited prey was about twice that of
      prey in other nutritional states, while at subsaturating prey concentrations, the
      ingestion rates of both C- and N-limited prey were higher than those of prey in
      other nutritional states. Over all prey concentrations, growth was most rapid on
      balanced and C-limited prey and generally lowest for P-limited prey. Due to the
      unimodal response of growth rate to abundance of N-limited prey, growth rate on N
      limited prey approached that obtained on balanced and C-limited prey when prey
      were available at intermediate abundances. The accumulation of recycled N
      increased with the growth rate of O. danica. Recycling of N was highest when O.
      danica was feeding upon P-limited prey. The accumulation of recycled P increased
      with growth rate for balanced and N-limited prey, but not for P-limited prey,
      which consistently had low accumulation of recycled P. The low growth rate and
      negligible recycling of P for O. danica preying on P-limited prey is consistent
      with the theory of ecological stoichiometry and resembles results found for
      crustacean zooplankton, especially in the genus Daphnia. Potentially, the major
      predators of bacterioplankton and a major predator of phytoplankton play
      analogous roles in the trophic dynamics and biogeochemistry of aquatic
      ecosystems.

PMID- 19184184
TI  - Cardiovascular complications associated with chronic active Epstein-Barr virus
      infection.
AB  - This study aimed to assess the outcome of cardiovascular diseases for patients
      with chronic active Epstein-Barr virus infection (CAEBV). The study enrolled 15
      patients (7 boys and 8 girls) who fulfilled the diagnostic criteria for CAEBV,
      including 10 patients with T-cell type and 3 patients with natural killer (NK)
      cell type. The median age at the CAEBV onset was 6.3 years (range, 1.2-17.8
      years). Regular cardiologic studies were performed during the median follow-up
      period of 8 years (range, 2-20 years). Nine patients (60%) had cardiac diseases
      including coronary artery lesion (CAL) (n = 4, 44%), decreased left ventricular
      ejection fraction and pericardial effusion in (n = 3, 33%), complete
      atrioventricular block (n = 1), and sudden arrest (n = 1). The frequency of fever
      (78%, p = 0.04) or cytopenias (100%, p = 0.01), as the major symptom among
      patients with cardiac complications, was higher than among those without
      complications. The median time from disease onset to detection of CAL was 3.4
      years (range, 1.8-8.6 years). The mean z-score increased to 3.98. Seven patients
      (78%) with cardiac complications died of disease progression, hematopoietic stem
      cell transplantation-related events, or both. In two patients, CAL regressed
      after allogeneic cord blood transplantation. Among CAEBV patients, CAL was the
      most common cardiac complication and could not be controlled without the
      eradication of EBV-infected T- and NK-cells.

PMID- 19184186
TI  - Water quality improvement policies: lessons learned from the implementation of
      Proposition O in Los Angeles, California.
AB  - This article evaluates the implementation of Proposition O, a stormwater cleanup
      measure, in Los Angeles, California. The measure was intended to create new
      funding to help the city comply with the Total Maximum Daily Load requirements
      under the federal Clean Water Act. Funding water quality objectives through a
      bond measure was necessary because the city had insufficient revenues to deploy
      new projects in its budget. The bond initiative required a supermajority vote
      (two-thirds of the voters), hence the public had to be convinced that such
      funding both was necessary and would be effective. The bond act language included
      project solicitation from the public, as well as multiple benefit objectives.
      Accordingly, nonprofit organizations mobilized to present projects that included
      creating new parks, using schoolyards for flood control and groundwater recharge,
      and replacing parking lots with permeable surfaces, among others. Yet few, if
      any, of these projects were retained for funding, as the city itself also had a
      list of priorities and higher technical expertise in justifying them as
      delivering water quality improvements. Our case study of the implementation of
      Proposition O points to the potentially different priorities for the renovation
      of urban infrastructure that are held by nonprofit organizations and city
      agencies and the importance of structuring public processes clearly so that there
      are no misimpressions about funding and implementation responsibilities that can
      lead to disillusionment with government, especially under conditions of fiscal
      constraints.

PMID- 19184187
TI  - History matters: relating land-use change to butterfly species occurrence.
AB  - Western European landscapes have drastically changed since the 1950s, with
      agricultural intensifications and the spread of urban settlements considered the
      most important drivers of this land-use/land-cover change. Losses of habitat for
      fauna and flora have been a direct consequence of this development. In the
      present study, we relate butterfly occurrence to land-use/land-cover changes over
      five decades between 1951 and 2000. The study area covers the entire Swiss
      territory. The 10 explanatory variables originate from agricultural statistics
      and censuses. Both state as well as rate was used as explanatory variables.
      Species distribution data were obtained from natural history collections. We
      selected eight butterfly species: four species occur on wetlands and four occur
      on dry grasslands. We used cluster analysis to track land-use/land-cover changes
      and to group communes based on similar trajectories of change. Generalized linear
      models were applied to identify factors that were significantly correlated with
      the persistence or disappearance of butterfly species. Results showed that
      decreasing agricultural areas and densities of farms with more than 10 ha of
      cultivated land are significantly related with wetland species decline, and
      increasing densities of livestock seem to have favored disappearance of dry
      grassland species. Moreover, we show that species declines are not only dependent
      on land-use/land-cover states but also on the rates of change; that is, the
      higher the transformation rate from small to large farms, the higher the loss of
      dry grassland species. We suggest that more attention should be paid to the rates
      of landscape change as feasible drivers of species change and derive some
      management suggestions.

PMID- 19184188
TI  - A system model for water management.
AB  - Although generally accepted as a necessary step to improve water management and
      planning, integrated water resources management (IWRM) methodology does not
      provide a clear definition of what should be integrated. The various water
      related issues that IWRM might encompass are well documented in the literature,
      but they are generally addressed separately. Therefore, water management lacks a
      holistic, systems-based description, with a special emphasis on the
      interrelations between issues. This article presents such a system model for
      water management, including a graphical representation and textual descriptions
      of the various water issues, their components, and their interactions. This model
      is seen as an aide-memoire and a generic reference, providing background
      knowledge helping to elicit actual system definitions, in possible combination
      with other participatory systems approaches. The applicability of the model is
      demonstrated through its application to two test case studies.

PMID- 19184189
TI  - Resource consumption and environmental impacts of the agrofood sector: life cycle
      assessment of italian citrus-based products.
AB  - Food production and consumption cause significant environmental burdens during
      the product life cycles. As a result of intensive development and the changing
      social attitudes and behaviors in the last century, the agrofood sector is the
      highest resource consumer after housing in the EU. This paper is part of an
      effort to estimate environmental impacts associated with life cycles of the
      agrofood chain, such as primary energy consumption, water exploitation, and
      global warming. Life cycle assessment is used to investigate the production of
      the following citrus-based products in Italy: essential oil, natural juice, and
      concentrated juice from oranges and lemons. The related process flowcharts, the
      relevant mass and energy flows, and the key environmental issues are identified
      for each product. This paper represents one of the first studies on the
      environmental impacts from cradle to gate for citrus products in order to suggest
      feasible strategies and actions to improve their environmental performance.

PMID- 19184190
TI  - Community perception of water quality in a mining-affected area: a case study for
      the Certej catchment in the Apuseni Mountains in Romania.
AB  - Mining-contaminated sites and the affected communities at risk are important
      issues on the agenda of both researchers and policy makers, particularly in the
      former communist block countries in Eastern Europe. Integrated analyses and
      expert based assessments concerning mining affected areas are important in
      providing solid policy guidelines for environmental and social risk management
      and mitigation. Based on a survey for 103 households conducted in a former mining
      site in the Certej Catchment of the Apuseni Mountains, western Romania, this
      study assesses local communities' perceptions on the quality of water in their
      living area. Logistic regression was used to examine peoples' perception on the
      quality of the main river water and of the drinking water based on several
      predictors relating to social and economic conditions. The results from the
      perception analysis were then compared with the measurements of heavy metal
      contamination of the main river and drinking water undertaken in the same study
      area. The findings indicate that perception and measurement results for the water
      quality in the Certej Catchment are convergent, suggesting an obvious risk that
      mining activities pose on the surface water. However, the perception on drinking
      water quality was little predicted by the regression model and does not seem to
      be so much related to mining as to other explanatory factors, such as special
      mineralogy of rock and soils or improper water treatment infrastructure, facts
      suggested by the measurements of the contaminants. Discussion about the
      implications of these joint findings for risk mitigation policies completes this
      article.

PMID- 19184191
TI  - Young adults and riding position: factors that affect mortality among inpatient
      adult motorcycle casualties: a major trauma center experience.
AB  - BACKGROUND: In Singapore, road traffic accidents (RTAs) are the second most
      common cause of deaths in trauma. Motorcycle casualties account for 54% of all
      fatalities. Studies have shown that the mean age of motorcycle casualties is
      significantly younger than that of other RTA victims. METHODS: We reviewed the
      mortality of all motorcycle casualties>or=16 years admitted to an acute hospital
      as emergencies from January 2004 to December 2006. To determine the impact of age
      on mortality, we divided our patients into two groups, one<or=21 years (younger
      group) and another>21 years (older group). A subset analysis based on riding
      position (driver versus passenger) was performed to determine the inpatient
      mortality rate in these two groups. RESULTS: There were 96 (14%) patients in the
      younger group and 586 (86%) patients in the older group. The mortality rate for
      younger motorcycle casualties was significantly higher (14.6% versus 8%; p=0.04).
      Also, there were significantly more passengers in the younger group (25% versus
      8.4%; p=0.0001). The mortality rate among young passengers was significantly
      higher than that among young drivers (29.2% versus 9.7%; p=0.019). Likewise, the
      mortality rate of the young passengers was also significantly higher than that
      among older passengers (29.2% versus 10.2%; p=0.04). CONCLUSIONS: Young
      motorcycle casualties have a significantly higher mortality rate than older
      motorcycle casualties. Young passengers have the highest mortality rate and
      contribute significantly to the death rate among young motorcycle casualties.

PMID- 19184192
TI  - A right accessory renal artery arising from a left additional common renal artery
      stem.

PMID- 19184193
TI  - Pancreas transplant venous thrombosis: role of endovascular interventions for
      graft salvage.
AB  - Venous thrombosis of pancreas transplant allografts often leads to graft loss. We
      evaluated the efficacy of emergent endovascular techniques to salvage thrombosed
      pancreatic allografts in a series of six patients. Of the 76 pancreas transplants
      performed between 2002 and 2006, six patients were diagnosed with venous
      thrombosis on MRI between 2 and 28 days posttransplant (mean, 9 days). Five
      patients were systemic-enteric (donor portal vein anastomosis to recipient iliac
      vein) and one patient was portal-enteric (donor portal vein anastomosis to
      recipient superior mesenteric vein). Conventional venography confirmed the
      diagnosis of venous thrombosis in all patients. One patient was treated with
      catheter-directed venous thrombolysis and balloon thrombectomy. Another patient
      was treated with rheolytic thrombectomy alone. The remaining four patients were
      treated with a combination of these mechanical and thrombolytic techniques.
      Completion venography revealed >50% clot reduction and resumption of venous
      drainage in all patients. One patient required additional intervention 16 days
      later for recurrent thrombosis. Two patients required metal stent placement for
      anastomotic stenoses or kinks. One patient required pancreatectomy 36 h after
      attempted salvage secondary to a major hemorrhage and graft necrosis. Two
      patients recovered pancreatic function initially but lost graft function at 8 and
      14 months, respectively, from severe chronic rejection. Patient survival was
      100%, long-term graft survival was 50%, rethrombosis rate was 16.6%, and graft
      loss from rejection was 33%. In conclusion, early recognition and treatment of
      venous thrombosis after pancreas transplantation has acceptable morbidity and no
      mortality using short-term endovascular pharmacomechanical therapy.

PMID- 19184194
TI  - Complementary use of NBCA with the Amplatzer vascular plug for embolization of a
      high-flow traumatic hepatic arteriovenous fistula.

PMID- 19184195
TI  - The clinical practice of interventional radiology: a European perspective.
AB  - The purpose of this study was to determine the current clinical environment in
      which interventional radiology (IR) is practiced throughout Europe. A survey,
      comprising 12 questions on IR clinical practice, was sent to 1800 CIRSE members.
      Members were asked to return one survey per department. Two hundred seventy-four
      departments returned completed questionnaires, 22% from the United Kingdom (n =
      60), 11% from Germany (n = 30), 8% from Austria (n = 23), and the remainder
      spread over Europe. Experts, with more than 10 years of IR experience, comprised
      74% of the survey group. Almost one-third of the radiologists dedicated more than
      80% of their clinical sessions to IR alone (27%; n = 75), with two-thirds
      practicing in a university teaching hospital setting (66%; n = 179). Few
      institutions have dedicated IR inpatient hospital beds (17%; n = 46), however, to
      compensate, day case beds are available (31%), IR admitting rights are in place
      (64% overall, 86% for in-patients, and 89% for day cases), and elective IR
      admissions can be made through other clinicians (87%). IR outpatient clinics are
      run at 26% of departments, with an average of two sessions per week. Dedicated
      nurses staff the majority of IR suites (82%), but clinical junior doctors are
      lacking (46%). Hospital management's refusing access to beds was the most
      commonly cited reason for not developing a clinical IR service (41%). In
      conclusion, there is marked variation across European centers in the current
      practice of IR. Half do not have dedicated junior doctors and only a small
      minority have inpatient hospital beds. If IR is to be maintained as a dedicated
      clinical specialty, these issues need to be addressed urgently.

PMID- 19184196
TI  - Stent-graft treatment for bleeding superior mesenteric artery pseudoaneurysm
      after pancreaticoduodenectomy.
AB  - We report two cases of intraperitoneal bleeding from superior mesenteric artery
      (SMA) pseudoaneurysm after pancreaticoduodenectomy for pancreatic head carcinoma.
      In both cases, a stent-graft was deployed on the main SMA to exclude
      pseudoaneurysm and to preserve blood flow to the bowel. Bleeding stopped after
      the procedure. One patient was able to be discharged but died from carcinoma
      recurrence 4 months later. The other patient died of sepsis and stent-graft
      infection 5 months later. These patients remained free of intraperitoneal
      rebleeding during the follow-up period.

PMID- 19184197
TI  - Radiofrequency ablation of abdominal wall endometrioma.
AB  - Extraperitoneal endometriosis is the presence of ectopic, functional endometrium
      outside the peritoneal cavity, and its occurrence is exceedingly rare. Diagnostic
      imaging--including ultrasound, duplex ultrasonography, and magnetic resonance
      imaging--in the preoperative assessment of patients with suspected abdominal wall
      endometriosis (AWE) is helpful for detection and accurate determination of the
      extent of disease. The treatment of choice for AWE is surgical excision. In
      addition, medical therapies can be used. We present one case of AWE treated with
      percutaneous radiofrequency ablation under ultrasound guidance. There were no
      major complications, and the patient's symptoms improved. In selected patients,
      radiofrequency ablation can be used safely for the treatment of AWE; however,
      further studies are needed to confirm this hypothesis.

PMID- 19184198
TI  - Embolization as an alternative treatment of insulinoma in a patient with multiple
      endocrine neoplasia type 1 syndrome.
AB  - Insulinoma is a rare neuroendocrine tumor, most commonly originating from the
      pancreas, which is either sporadic or familial as a component of multiple
      endocrine neoplasia type 1 syndrome (MEN1). It is characterized by increased
      insulin secretion leading to hypoglycemia. Surgical removal is considered the
      treatment of choice, with limited side effects and relatively low morbidity and
      mortality, both being improved by the laparoscopic procedure. We present the case
      of a 30-year-old patient with MEN1 and recurrent insulinoma with severe
      hypoglycemic episodes who could not be surgically treated due to the adherence of
      the tumor to large blood vessels and to prior multiple surgical operations. He
      was treated by repeated embolization using spherical polyvinyl alcohol particles,
      resulting in shrinkage of the tumor, improvement of the frequency and severity of
      the hypoglycemic episodes, and better quality of life.

PMID- 19184199
TI  - Challenging a myth: directional atherectomy.

PMID- 19184200
TI  - Demographics and outcomes at American Society for Metabolic and Bariatric Surgery
      Centers of Excellence.
AB  - INTRODUCTION: Surgery is currently an effective long-term therapy for morbid
      obesity and its complications. A variety of surgical procedures can now offer
      durable and safe weight control as well as previously unrealized full remission
      of costly comorbidities. This is a preliminary investigation of patient
      characteristics and outcomes at Bariatric Surgery Centers of Excellence) (BSCOE)
      hospitals. METHODS AND PROCEDURES: Data were analyzed from 235 American Society
      for Metabolic and Bariatric Surgery (ASMBS) BSCOE hospitals receiving Full
      Approval status from August 2005 to May 2007. Metrics for the 66,339 bariatric
      surgeries performed at these hospitals included type, volume and distribution of
      various bariatric surgical procedures performed at each hospital, patient
      demographics, payer information, and adverse outcomes. RESULTS: Data from these
      analyses demonstrate significant differences in terms of surgical procedure
      selection (laparoscopic gastric bypass 61%), patient demographics (females 83%,
      White 60%, mean age 43 years) and type of payer (private insurance 78%), and
      adverse outcomes (readmission 5%, re-operation 2%, mortality 0.36%). CONCLUSIONS:
      The collective performance of ASMBS BSCOE hospitals in bariatric outcomes of
      readmissions, re-operations, and mortality are equivalent to, or more favorable,
      than currently reported outcomes. However, risk assessment and risk adjustment of
      the patients and each of the bariatric procedures will be necessary to
      appropriately evaluate these rates.

PMID- 19184201
TI  - The economic impact of morbid obesity.

PMID- 19184202
TI  - Feasibility and accuracy of second-look laparoscopy after gastrectomy for gastric
      cancer.
AB  - BACKGROUND: A better method for detecting early peritoneal progression is needed.
      This study evaluated the feasibility and accuracy of second-look laparoscopy for
      patients with gastric cancer treated using systemic chemotherapy after
      gastrectomy. METHODS: Second-look laparoscopy was conducted for patients who had
      no clinical evidence of distant metastases but had peritoneal metastases or
      positive peritoneal cytology results without visible metastatic disease at
      initial surgery, patients who underwent systemic chemotherapy over a 6-month
      period after surgery, and patients who had no clinical evidence of disease based
      on imaging study after completion of primary chemotherapy. RESULTS: Between
      November 2004 and April 2008, 21 patients underwent second-look laparoscopy. At
      the initial surgery, 13 of these patients underwent total gastrectomy and 8
      patients underwent distal gastrectomy. One or two sheets of adhesion barrier were
      received by 18 patients. The median interval between initial surgery and second
      look laparoscopy was 9.8 months (range, 6.6-17.5 months). All second-look
      procedures were completed laparoscopically, and no patients required conversion
      to laparotomy. None of the 21 patients experienced postlaparoscopy complications.
      Whereas 12 patients showed no pathologic evidence of disease, 9 patients showed
      disease at second-look laparoscopy. There was a significant difference in median
      survival between the groups with negative and positive results (p = 0.017). The
      median survival for the negative group has not been determined. All the patients
      in the positive group received further chemotherapy while showing a good
      performance status (PS). Six patients were PS 0, and 3 patients were PS 1. The
      median survival time for this group was 10.1 months. CONCLUSIONS: Second-look
      laparoscopy was a safe and promising approach to reassessment of peritoneal
      disease for patients with gastric cancer. The incidence of complications was low,
      particularly in this group of patients, all of whom had undergone prior
      gastrectomy.

PMID- 19184203
TI  - Minimally invasive colon resection is associated with a transient increase in
      plasma sVEGFR1 levels and a decrease in sVEGFR2 levels during the early
      postoperative period.
AB  - INTRODUCTION: Plasma vascular endothelial growth factor (VEGF) levels are
      elevated for 2-4 weeks after minimally invasive colorectal resection (MICR). VEGF
      induces wound and tumor angiogenesis by binding to endothelial cell (EC)-bound
      VEGF-receptor 1 (VEGFR1) and VEGFR2. Soluble receptors (sVEGFR1, sVEGFR2)
      sequester VEGF in the blood and decrease VEGF's proangiogenic effect. The
      importance of the MICR-related VEGF changes depends on the effect of surgical
      procedures on sVEGFR1 and sVEGFR2; this study assessed levels of these proteins
      after MICR for benign indications. METHODS: Blood samples were taken (n=39)
      preoperatively (preop) and on postoperative days (POD) 1 and 3; in most cases a
      fourth sample was drawn between POD 7 and 30. sVEGFR1 and sVEGFR2 levels were
      measured via enzyme-linked immunosorbent assay (ELISA), which detects free and
      VEGF bound soluble receptor. Late samples were bundled into POD 7-13 and POD 14
      30 time points. Results are reported as mean and standard deviation. The data was
      assessed with paired-samples t-test. RESULTS: Preop, mean plasma sVEGFR2 level
      (9,203.7+/-1,934.3 pg/ml) was significantly higher than the sVEGFR1 value
      (132.5+/-126.2 pg/ml). sVEGFR2 levels were significantly lower on POD 1
      (6,957.8+/-1,947.7 pg/ml,) and POD 3 (7,085.6+/-2,000.2 pg/ml), whereas sVEGFR1
      levels were significantly higher on POD 1 (220.0+/-132.8 pg/ml) and POD 3
      (182.7+/-102.1 pg/ml) versus preop results. No differences were found on POD 7-13
      or 14-30. CONCLUSIONS: sVEGFR2 values decreased and sVEGFR1 levels increased
      early after MICR; due to its much higher baseline, the sVEGFR2 changes dominate.
      The net result is less VEGF bound to soluble receptor and more free plasma VEGF.

PMID- 19184204
TI  - Comparison of those who succeed in losing significant excessive weight after
      bariatric surgery and those who fail.
AB  - BACKGROUND: Gastric bypass and adjustable gastric banding currently are the most
      commonly performed weight loss surgeries. The results are encouraging for most
      patients, but some patients have a better experience than others. This report
      aims to define differences between those who succeeded and those that failed to
      lose significant excessive weight after bariatric surgery. METHODS: The authors
      retrospectively reviewed their database over the past 4 years. They studied 484
      bariatric patients who had 1 year of follow-up evaluation. Success was defined as
      more than 50% excess weight loss (EWL) and failure as less than 30% EWL.
      Student's t-tests were performed between the groups of bypass patients, band
      patients, men, women, whites, and minorities. RESULTS: An overall success rate of
      58% and a failure rate of 15% were observed. The successful group was
      significantly younger. The starting body mass index (BMI) was significantly lower
      for the successful band patients. The starting excess weight was significantly
      less in both the successful band and bypass groups, as was the starting weight.
      The successful whites were significantly younger, and the starting BMI was
      significantly lower in the successful minority group. The unsuccessful bypass
      patients and whites were significantly taller than the successful group. Gender
      was not a significant variable in success or failure regardless of procedure.
      CONCLUSION: Without consideration for the procedure performed, the patients who
      successfully lost weight were younger. The unsuccessful band patients had a
      higher starting BMI, whereas the successful band and bypass patients had lower
      average starting and excess weights. The successful bypass patients were
      significantly shorter. Among whites, the successful patients were significantly
      younger and shorter. The successful minorities had a lower starting BMI. These
      variables give further insight into the complexity of successful excess weight
      loss.

PMID- 19184205
TI  - Shortened OR time and decreased patient risk through use of a modular surgical
      instrument with artificial intelligence.
AB  - With a limited number of access ports, minimally invasive surgery (MIS) often
      requires the complete removal of one tool and reinsertion of another. Modular or
      multifunctional tools can be used to avoid this step. In this study, soft
      computing techniques are used to optimally arrange a modular tool's functional
      tips, allowing surgeons to deliver treatment of improved quality in less time,
      decreasing overall cost. The investigators watched University Medical Center
      surgeons perform MIS procedures (e.g., cholecystectomy and Nissen fundoplication)
      and recorded the procedures to digital video. The video was then used to analyze
      the types of instruments used, the duration of each use, and the function of each
      instrument. These data were aggregated with fuzzy logic techniques using four
      membership functions to quantify the overall usefulness of each tool. This
      allowed subsequent optimization of the arrangement of functional tips within the
      modular tool to decrease overall time spent changing instruments during simulated
      surgical procedures based on the video recordings. Based on a prototype and a
      virtual model of a multifunction laparoscopic tool designed by the investigators
      that can interchange six different instrument tips through the tool's shaft, the
      range of tool change times is approximately 11-13 s. Using this figure, estimated
      time savings for the procedures analyzed ranged from 2.5 to over 32 min, and on
      average, total surgery time can be reduced by almost 17% by using the
      multifunction tool.

PMID- 19184206
TI  - Endoscopic full-thickness resection with laparoscopic assistance as hybrid NOTES
      for gastric submucosal tumor.
AB  - BACKGROUND AND OBJECTIVE: Laparoscopic wedge resection using a linear stapler is
      widely accepted as a treatment for gastric submucosal tumor (SMT). Although this
      surgery is simple, it can lead to excessive normal tissue removal. To avoid the
      latter, we have introduced endoscopic full-thickness resection with laparoscopic
      assistance, known as laparoscopy-assisted endoscopic full-thickness resection
      (LAEFR). Herein, we present the preliminary results of LAEFR for gastric SMT
      patients. METHODS: Four patients with gastric SMT underwent LAEFR. LAEFR consists
      of four major procedures: (1) a circumferential incision as deep as the
      submucosal layer around the lesion by the endoscopic submucosal dissection
      technique, (2) endoscopic full-thickness (from the muscle layer to the serosal
      layer) incision around the three-fourths or two-thirds circumference on the above
      mentioned submucosal incision under laparoscopic supervision, (3) completion of
      the full-thickness incision laparoscopically from inside the peritoneal cavity,
      and (4) handsewn closure of the gastric-wall defect. RESULTS: LAEFR was
      successfully carried out without any intraoperative or postoperative adverse
      events. Mean operating time and estimated blood loss were 201 min and 27 mL,
      respectively. Contrast roentgenography on postoperative day 3 showed neither
      gastric deformity nor disturbance of gastric emptying in all the patients.
      CONCLUSIONS: LAEFR may be considered one of the so-called hybrid natural orifice
      transluminal endoscopic surgery (NOTES) techniques because a peroral endoscope
      advances into the peritoneal cavity. LAEFR enabled whole-layer excision as small
      as possible with an adequate margin. LAEFR is a safe and minimally invasive
      treatment for patients with gastric SMT, and could be a more reasonable and
      economical alternative to other laparoscopic procedures.

PMID- 19184207
TI  - Sentinel node mapping during laparoscopic distal gastrectomy for gastric cancer.

PMID- 19184208
TI  - General complications following laparoscopic-assisted gastrectomy and analysis of
      techniques to manage them.
AB  - BACKGROUND: The aim of this study was to assess the complications associated with
      the laparoscopic treatment of gastric cancer and to discuss their management.
      METHODS: From March 2004 to June 2007, 302 patients affected by gastric
      adenocarcinoma underwent laparoscopy-assisted gastrectomy. Of the 302 gastric
      malignancy cases, distal gastrectomy was performed in 161 cases, proximal
      gastrectomy in 62 cases, and total gastrectomy in 79 cases. In all cases, D1 or
      D2 lymph node dissection was performed according to the recommended procedures of
      the Japanese Gastric Cancer Association. RESULTS: Duration of surgery ranged from
      180 to 310 min (median 230 min). There were no deaths during surgery and no
      anesthesiology complications in our series. We recorded 15 (4.97%) intraoperative
      complications: one transverse colon perforation, one lesion of the liver, two
      cases of splenic laceration, one injury of cystic artery leading to gangrene of
      the gallbladder, nine cases of hemorrhage, and one biliary tract injury.
      Conversion to open surgery was necessary in only five cases (1.7%). We recorded
      21 (7.0%) postoperative complications: four cases of intra-abdominal bleeding,
      seven cases of duodenal stump leakage, one case of duodenal stump leakage
      followed by arteriole hemorrhage due to fundus of the stomach, two cases of acute
      pancreatitis, one case of lymphatic fistula, one case of anastomotic fistula,
      three cases of delayed gastric emptying, and two cases of obstruction of afferent
      loop. Six patients underwent reoperation, of whom two died after the procedure
      while the other four recovered postoperatively; other postoperative complications
      were treated conservatively. The overall operative morbidity and mortality rates
      were 11.9% and 0.7%, respectively. CONCLUSION: Our results show that laparoscopic
      assisted gastrectomy is an adequate treatment for gastric cancer as long as the
      indications are controlled and only suitable cases are enrolled in the series.
      The complication rate is low enough to be acceptable. Most complications can be
      treated effectively via conservative treatment, and only a small number of cases
      require reoperation.

PMID- 19184209
TI  - Pressure-controlled versus volume-controlled ventilation during one-lung
      ventilation in the prone position for robot-assisted esophagectomy.
AB  - BACKGROUND: The prone position during robotic esophageal mobilization for
      minimally invasive esophagectomy (MIE) provides several advantages with regards
      to operative times, surgeon ergonomics, and surgical view; however, this
      technique requires one-lung ventilation (OLV). There are no guidelines about
      ventilatory modes during OLV in the prone position. We investigated the effects
      of volume-controlled (VCV) and pressure-controlled ventilation (PCV) on
      oxygenation and intrapulmonary shunt during OLV in the prone position in patients
      who underwent robot-assisted esophagectomy. METHODS: Eighteen patients, no major
      obstructive or restrictive pulmonary disease, were allocated randomly to one of
      two groups. In the first group (n = 9), OLV was started by VCV and the ventilator
      was switched to PCV after 30 minutes. In the second group (n = 9), the modes of
      ventilation were performed in the opposite order in the prone position.
      Hemodynamic and respiratory variables were obtained during OLV at the end of each
      ventilatory mode. RESULTS: There were no significant differences in arterial
      oxygen tension (PaO(2)), airway pressures, dynamic lung compliance, or
      physiologic dead space (Vd/Vt) during OLV between PCV and VCV in the prone
      position. Intrapulmonary shunt (Qs/Qt) was significantly lower with VCV than with
      PCV during OLV in the prone position (p = 0.044). CONCLUSION: PCV provides no
      advantages compared with VCV with regard to respiratory and hemodynamic variables
      during OLV in the prone position. Either ventilatory mode can be safely used for
      patients who undergo robot-assisted esophagectomy and who have normal body mass
      index and preserved pulmonary function.

PMID- 19184210
TI  - The role of intraoperative carbon dioxide insufflating upper gastrointestinal
      endoscopy during laparoscopic surgery.
AB  - BACKGROUND: Intraoperative endoscopy (IOE) is a useful adjunct during
      laparoscopic gastrointestinal (GI) surgery. However, one potential hazard of IOE
      is a prolonged bowel distension due to insufflated air, which may cause
      obstructed surgical exposure and increased postoperative abdominal pain.
      Recently, carbon dioxide (CO(2)), with its rapid absorptive nature, has been
      proven effective to minimize prolonged bowel distension in
      ambulatory/intraoperative colonoscopy. The objectives were to assess the
      feasibility, safety, and efficacy of CO(2)-insufflating upper GI IOE during
      laparoscopic surgery. METHODS: A historical comparison study was performed on the
      initial ten consecutive patients who underwent CO(2)-insufflating upper GI IOE
      (CO(2)-IOE) during laparoscopic surgery. The control group consisted of the past
      12 consecutive patients who underwent conventional air-insufflating upper GI IOE
      (air-IOE) during laparoscopic surgery. The following parameters were compared
      between the two groups: (1) patient demographics; (2) feasibility (% completion
      of IOE); (3) safety (complications related to IOE, impacts on cardiopulmonary
      status, including systemic blood pressure, heart rate, and end-tidal CO(2)); (4)
      efficacy (postoperative residual intestinal gas, time to resume oral intake, and
      bowel movement). The amounts of post-IOE residual intestinal gas were evaluated
      and classified on the immediate postoperative abdominal radiographs in a blinded
      manner. RESULTS: Patient demographics were comparable between the two groups. IOE
      was completed in both groups without complications. Adverse effects on
      cardiopulmonary status were not observed during simultaneous intraperitoneal and
      intraluminal CO(2) insufflation. In the air-IOE group, one patient was converted
      to open surgery because of inadequate surgical exposure from prolonged distension
      of the downstream bowel. The patients in the CO(2)-IOE group had significantly
      lower grade of postoperative bowel distension than the control group.
      Postoperative oral intake was resumed earlier in the CO(2)-IOE group. CONCLUSION:
      CO(2)-insufflating upper GI IOE during laparoscopic surgery is feasible, safe,
      and has a practical advantage in minimizing post-IOE bowel distension compared
      with conventional air-insufflating upper GI IOE.

PMID- 19184211
TI  - Safety, feasibility, and short-term outcomes of laparoscopically assisted primary
      ileocolic resection for Crohn's disease.
AB  - BACKGROUND: Outcomes of laparoscopic resection for ileocecal Crohn's disease have
      been reported previously in smaller studies, suggesting its short-term advantages
      over open surgery. This study assessed the safety and recovery parameters in the
      largest, consecutive, single-institution series to date. METHODS: Consecutive
      patients undergoing laparoscopically assisted primary ileocolic resection for
      Crohn's disease between 1994 and 2006 were identified in an institutional
      prospectively collected database. Operative and postoperative outcomes at 30 days
      were studied. RESULTS: In this study, 109 patients (35 men) with a mean age of 35
      +/- 14 years and a mean body mass index (BMI) of 25 +/- 6 kg/m(2) were
      identified. The main indications for surgery were medically refractory disease
      (63%) and fibrous stenosis (27%). In 41% of the cases, previous abdominal surgery
      had been performed. The surgery had a mean duration of 150 +/- 45 min and a
      conversion rate of 6%. The overall 30-day morbidity rate was 11%, and the
      reoperation rate was 1%. The mortality rate was 0%. The median postoperative
      hospital stay was 4 days (range, 2-15 days). CONCLUSIONS: This series, the
      largest reported to date, concurs with recent metaanalyses findings that
      laparoscopically assisted primary ileocecal resection for Crohn's disease is safe
      and feasible, resulting in better short-terms outcomes than open resection. This
      operation is therefore the procedure of choice for Crohn's disease at our
      institutions.

PMID- 19184212
TI  - Retrievable inferior vena cava filters in high-risk patients undergoing bariatric
      surgery.
AB  - BACKGROUND: Placement of retrievable inferior vena cava filters (rIVCF) may be
      beneficial in high-risk morbidly obese patients undergoing bariatric procedures.
      Patients with a previous history of venous thromboembolism (VTE) are at high risk
      for postoperative deep venous thrombosis (DVT) and pulmonary embolism (PE).
      METHODS: A prospective database of bariatric surgery patients was studied from
      April 2003 to May 2007. A total of 791 patients underwent bariatric procedures,
      of which 30 (4%) had a previous history of VTE. These patients underwent
      preoperative venous duplex and concurrent placement of a rIVCF. Patient
      demographics and clinical outcomes were examined. RESULTS: Thirty patients (12
      (40%) men) had a mean age of 49 +/- 8 years and a mean body mass index of 50 +/-
      8 kg/m(2). Sixteen patients (53%) underwent laparoscopic Roux-en-Y gastric
      bypass, ten (33%) underwent laparoscopic adjustable gastric band, and four (14%)
      underwent open Roux-en-Y gastric bypass. Mean operative time, including rIVCF
      placement, was 162 +/- 66 minutes. All patients had successful rIVCF placement
      with standard perioperative chemoprophylaxis. Twenty-nine patients (97%) had a
      follow-up ultrasound on postoperative day (POD) 19 +/- 25. Six patients (21%) had
      recurrent DVT. Twenty-seven patients (90%) underwent a follow-up venogram, and
      four patients (15%) had significant thrombus in the rIVCF. Retrieval was
      successful in 21 patients (70%). Nine patients (30%) did not undergo retrieval:
      four had significant thrombus in the filter, four had an above-knee DVT, and one
      due to technical reasons. We observed one complication with a DVT at the access
      site and no PE or mortality. CONCLUSIONS: We observed a 21% incidence of
      recurrent DVT and 15% incidence of thrombus in the IVCF, yet no PE occurred. IVCF
      retrieval was successful in 70% with one complication. Concurrent IVCF placement
      is safe, feasible, and an effective preventative measure in high-risk morbidly
      obese patients. We recommend the use of rIVCFs in conjunction with standard VTE
      prophylaxis in this patient population.

PMID- 19184213
TI  - Bands and bypasses: statistical limitations of regression analysis.

PMID- 19184214
TI  - Is Oddi sphincterotomy an indication for hepatolithiasis?
AB  - BACKGROUND: The purpose of treatment for hepatolithiasis is reducing recurrent
      cholangitis. This study was designed to determine the long-term outcome of Oddi
      sphincterotomy for hepatolithiasis. METHODS: Thirty-two consecutive
      hepatolithiasis patients, including 15 cases that had undergone conventional open
      surgical transduodenal sphincteroplasty (COSTS) and 17 cases with endoscopic
      sphincterotomy (EST), were followed up for a long term. We compared the post
      treatment rates of recurrent cholangitis and acute cholangitis severe type (ACST)
      with the ones of pretreatment in each group, respectively. Paired chi(2) test was
      used. RESULTS: In the COSTS group, neither the post-operative rate of recurrent
      cholangitis (86.7%, 13/15 vs. 100%, 15/15) nor ACST (26.7%, 4/15 vs. 46.7%, 7/15)
      decreased (p > 0.05) compared with before the operation. In the EST group, the
      situation was the same: neither the rate of post-EST recurrent cholangitis
      (76.5%, 13/17 vs. 82.4%, 14/17) nor ACST (29.4%, 5/17 vs. 23.5%, 4/17) were
      reduced significantly (p > 0.05). CONCLUSIONS: Both eradication of hepatobiliary
      lesions and keeping Oddi sphincter intact should be emphasized in the management
      of hepatolithiasis. Neither COSTS nor EST is an effective method or can achieve
      the goal of reducing cholangitis for hepatolithiasis.

PMID- 19184215
TI  - Minimally invasive video-assisted thyroidectomy compared with conventional
      thyroidectomy in a general surgery department.
AB  - BACKGROUND: We retrospectively evaluated a series of patients who underwent
      minimally invasive video-assisted thyroidectomy (MIVAT) to define its advantages
      or disadvantages. METHODS: Between May 2005 and March 2008, 68 patients underwent
      MIVAT. Sixty-nine patients who underwent conventional thyroidectomy (CT) during
      the period before the introduction of the MIVAT technique in our department
      chosen with the same inclusion criteria used for MIVAT-served as matched
      controls. The eligibility criteria for both groups was thyroid nodules < or = 35
      mm, thyroid volume < 25 ml, no thyroiditis, and no previous surgery. RESULTS:
      Forty-five MIVAT and 43 CT patients underwent hemithyroidectomy. Twenty-three
      MIVAT and 26 CT patients underwent total thyroidectomy. No differences were found
      in terms of complications, operative time, and radicality of the procedure.
      Patients who underwent MIVAT experienced significantly less pain, better cosmetic
      results, and shorter hospital stay than patients who underwent conventional
      surgery CONCLUSION: The MIVAT technique, in selected patients, seems to be a
      valid option for thyroidectomy and even preferable to conventional surgery
      because of its significant advantages, especially in terms of cosmetic results,
      postoperative pain, and postoperative recovery.

PMID- 19184216
TI  - Endoscopic therapy for esophageal perforation or anastomotic leak with a self
      expandable metallic stent.
AB  - BACKGROUND: Leaks of the esophagus are associated with a high mortality rate and
      need to be treated as soon as possible. Therapeutic options are surgical repair
      or resection or conservative management with cessation of oral intake and
      antibiotic therapy. We evaluated an alternative approach that uses self
      expandable metallic stents (SEMS). METHODS: Between 2002 and 2007, 31 consecutive
      patients with iatrogenic esophageal perforation (n = 9), intrathoracic
      anastomotic leak after esophagectomy (n = 16), spontaneous tumor perforation (n =
      5), and esophageal ischemia (n = 1) were treated at our institution. All were
      treated with endoscopic placement of a covered SEMS. Stent removal was performed
      4 to 6 weeks after implantation. To exclude continuous esophageal leak after SEMS
      placement, radiologic examination was performed after stent implantation and
      removal. RESULTS: SEMS placement was successful in all patients and a
      postinterventional esophagogram demonstrated full coverage of the leak in 29
      patients (92%). In two patients, complete sealing could not be achieved and they
      were referred to surgical repair. Stent migration was seen in only one patient
      (3%). After removal, a second stent with larger diameter was placed and no
      further complication occurred. Two patients died: one due to myocardial
      infarction and one due to progressive ischemia of the esophagus and small bowl as
      a consequence of vascular occlusion. Stent removal was performed within 6 weeks,
      and all patients had radiologic and endoscopic evidence of esophageal healing.
      CONCLUSIONS: Implantation of covered SEMS in patients with esophageal leak or
      perforation is a safe and feasible alternative to operative treatment and can
      lower the interventional morbidity rate.

PMID- 19184218
TI  - E-NOTES appendectomy versus transvaginal appendectomy: similar cosmetic results
      but shorter complete recovery?

PMID- 19184217
TI  - Effectiveness for pain after laparoscopic cholecystectomy of 0.5% bupivacaine
      soaked Tabotamp placed in the gallbladder bed: a prospective, randomized,
      clinical trial.
AB  - BACKGROUND: Some scientific studies, with controversial results, have evaluated
      the efficacy in reducing pain of some different local anesthetic molecules, which
      were administered at different dosages and in different ways. The primary goal of
      this randomized, controlled, prospective study (Clinical Trials.gov ID
      NCT00599144) was to assess the effectiveness of 0.5% bupivacaine for pain control
      after video-laparoscopic cholecystectomy at its optimal dosage of 2 mg/kg
      infiltrated in the muscular fasciae of the trocars, or positioned in the
      gallbladder soaking a sheet of regenerated oxidized cellulose (Tabotamp).
      METHODS: A total of 45 patients underwent elective video-laparoscopic
      cholecystectomy. They were randomized in three groups each made of 15 patients:
      group A (bupivacaine-soaked Tabotamp positioned in the gallbladder bed), group B
      (bupivacaine infiltrated in the muscular fasciae of the trocars' seat), group C
      (control group, not using local anesthetic). Six and twenty-four hours after the
      intervention, the nature of the pain and its intensity were recorded with the use
      of a Visual Analogue Scale (VAS). RESULTS: Six hours after the intervention, VAS
      average was 29.6 +/- 10.92 for group A, 25.86 +/- 16.06 for group B, and 36.13 +/
      16.62 for group C. At 24 h, we recorded 19.26 +/- 15.81, 18.53 +/- 12.3, and
      20.46 +/- 20.08 for groups A, B, and C, respectively (p > 0.05). Comparing groups
      A and B between them and with the control group at 6 and 24 h, we deduced how
      only the first group showed a statistically significant advantage (p < 0.05) in
      reducing visceral and shoulder pain compared with the two other groups. Wound
      infiltration resulted in being statistically favorable in reducing parietal pain
      only when compared with Group A. For groups A and B, bupivacaine significantly
      reduced the use of postoperative pain killers. CONCLUSION: Bupivacaine, either
      infiltrated in trocars' wounds or kept soaked in a regenerated oxidized cellulose
      sheet positioned in the gallbladder bed, although safe and not economically
      demanding, can increase postoperative comfort.

PMID- 19184220
TI  - Active nematocyst isolation via nudibranchs.
AB  - Cnidarian venoms are potentially valuable tools for biomedical research and drug
      development. They are contained within nematocysts, the stinging organelles of
      cnidarians. Several methods exist for the isolation of nematocysts from cnidarian
      tissues; most are tedious and target nematocysts from specific tissues. We have
      discovered that the isolated active nematocyst complement (cnidome) of several
      sea anemone (Cnidaria: Anthozoa) species is readily accessible. These nematocysts
      are isolated, concentrated, and released to the aqueous environment as a by
      product of aeolid nudibranch Spurilla neapolitana cultures. S. neapolitana feed
      on venomous sea anemones laden with stinging nematocysts. The ingested stinging
      organelles of several sea anemone species are effectively excreted in the
      nudibranch feces. We succeeded in purifying the active organelles and inducing
      their discharge. Thus, our current study presents the attractive possibility of
      using nudibranchs to produce nematocysts for the investigation of novel marine
      compounds.

PMID- 19184221
TI  - Use of a wiki as a radiology departmental knowledge management system.
AB  - Information technology teams in health care are tasked with maintaining a variety
      of information systems with complex support requirements. In radiology, this
      includes picture archive and communication systems, radiology information
      systems, speech recognition systems, and other ancillary systems. Hospital
      information technology (IT) departments are required to provide 24 x 7 support
      for these mission-critical systems that directly support patient care in
      emergency and other critical care departments. The practical know-how to keep
      these systems operational and diagnose problems promptly is difficult to maintain
      around the clock. Specific details on infrequent failure modes or advanced
      troubleshooting strategies may reside with only a few senior staff members. Our
      goal was to reduce diagnosis and recovery times for issues with our mission
      critical systems. We created a knowledge base for building and quickly
      disseminating technical expertise to our entire support staff. We used an open
      source, wiki-based, collaborative authoring system internally within our IT
      department to improve our ability to deliver a high level of service to our
      customers. In this paper, we describe our evaluation of the wiki and the ways in
      which we used it to organize our support knowledge. We found the wiki to be an
      effective tool for knowledge management and for improving our ability to provide
      mission-critical support for health care IT systems.

PMID- 19184219
TI  - Highly unsaturated fatty acid synthesis in Atlantic salmon: characterization of
      ELOVL5- and ELOVL2-like elongases.
AB  - Fish species vary in their capacity to biosynthesize the n-3 long-chain
      polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic (EPA) and docosahexaenoic
      (DHA) acids that are crucial to the health of higher vertebrates. The synthesis
      of LC-PUFA involves enzyme-mediated fatty acyl desaturation and elongation.
      Previously, a complementary DNA (cDNA) for an elongase, now termed elovl5a, had
      been cloned from Atlantic salmon. Here, we report on the cloning of two new
      elongase cDNAs: a second elovl5b elongase, corresponding to a 294-amino-acid (aa)
      protein, and an elovl2-like elongase, coding for a 287-aa protein, characterized
      for the first time in a nonmammalian vertebrate. Heterologous expression in yeast
      showed that the salmon Elovl5b elongated C18 and C20 PUFA, with low activity
      towards C22, while Elovl2 elongated C20 and C22 PUFA with lower activity towards
      C18 PUFA. All three transcripts showed predominant expression in the intestine
      and liver, followed by the brain. Elongase expression showed differential
      nutritional regulation. Levels of elovl5b and particularly of elovl2, but not of
      elovl5a, transcripts were significantly increased in liver of salmon fed
      vegetable oils (VO) compared to fish fed fish oil (FO). Intestinal expression
      showed a similar pattern. Phylogenetic comparisons indicate that, in contrast to
      salmon and zebra fish, Acanthopterygian fish species lack elovl2 which is
      consistent with their negligible ability to biosynthesize LC-PUFA and to adapt to
      VO dietary inclusion, compared to predominantly freshwater salmonids. Thus, the
      presence of elovl2 in salmon explains the ability of this species to
      biosynthesize LC-PUFA and may provide a biotechnological tool to produce enhanced
      levels of LC-PUFA, particularly DHA, in transgenic organisms.

PMID- 19184222
TI  - A multistage registration method using texture features.
AB  - We present a novel, multistage registration method based on Laws' texture
      features. In general, a large number of texture features may be extracted from
      the original intensity images. For each of the texture features, a criterion
      function that measures the similarity between the images may be derived. The
      proposed registration method consists of two major steps. In the first step, a
      dataset of images with the corresponding gold standard is used. In this step, the
      selection and ranking of the texture features for registration is made. The
      selection and ranking of the features is based on their robustness, accuracy, and
      capture range. The selected features are then entered in the second step, where
      the actual registration is performed using a sequence of registration stages. Our
      method is based on the selection of the most robust feature for the first
      registration stage and the selection of accurate feature(s) for the subsequent
      stages. The texture features are daisy-chained so that the accuracy of the
      previous feature is sufficient for the capture range of the next feature. We
      tested our method on 11 2D image pairs containing digital reconstructed
      radiographs and electron portal imaging modalities, which were difficult to
      register using intensity features alone. With our method, we have successfully
      registered 75% of the initial displacements, ranging from 5 to 7.5 mm, with the
      target-registration error below 3 mm, whereas the traditional intensity-based
      approach delivered only 15% successfully registered cases.

PMID- 19184223
TI  - XML-based DICOM data format.
AB  - To enhance the readability, improve the structure, and facilitate the sharing of
      digital imaging and communications in medicine (DICOM) files, this research
      proposed one kind of XML-based DICOM data format. Because XML Schema offers great
      flexibility for expressing constraints on the content model of elements, we used
      it to describe the new format, thus making it consistent with the one originally
      defined by DICOM. Meanwhile, such schemas can be used in the creation and
      validation of the XML-encoded DICOM files, acting as a standard for data
      transmission and sharing on the Web. Upon defining the new data format, we
      started with representing a single data element and further improved the whole
      data structure with the method of modularization. In contrast to the original
      format, the new one possesses better structure without loss of related
      information. In addition, we demonstrated the application of XSLT and XQuery. All
      of the advantages mentioned above resulted from this new data format.

PMID- 19184224
TI  - Enzyme induction as a possible mechanism for latex-mediated insect resistance in
      romaine lettuce.
AB  - Plant latex is a known storehouse of various secondary metabolites with
      demonstrated negative impact on insect fitness. A romaine lettuce cultivar,
      "Valmaine", possesses a high level of latex-mediated resistance against the
      banded cucumber beetle, Diabrotica balteata LeConte (Coleoptera: Chrysomelidae),
      compared to a closely related cultivar "Tall Guzmaine". Latex from damaged
      Valmaine plants was much more deterrent to adult D. balteata feeding than latex
      from undamaged plants when applied to the surface of artificial diet under choice
      conditions; no such difference was found in choice tests with latex from damaged
      and undamaged Tall Guzmaine plants. The intensities of whiteness and browning
      were significantly higher in Valmaine latex than in Tall Guzmaine latex. The
      activities of three enzymes (phenylalanine ammonia lyase, polyphenol oxidase, and
      peroxidase) significantly increased over time in latex from damaged Valmaine
      plants (i.e., 1, 3, and 6 days after feeding initiation), but they remained the
      same in Tall Guzmaine latex. The constitutive levels of phenylalanine ammonia
      lyase and polyphenol oxidase also were significantly higher in Valmaine latex
      than in Tall Guzmaine latex. These studies suggest that Valmaine latex chemistry
      may change after plant damage due to increased activity of inducible enzymes and
      that inducible resistance appears to act synergistically with constitutive
      resistance against D. balteata.

PMID- 19184225
TI  - Factors influencing responses to alarm pheromone by larvae of invasive cane
      toads, Bufo marinus.
AB  - If pheromonal communication systems of invasive species differ from those of
      native biota, it may be possible to control the invader by exploiting that
      difference. When injured, the larvae of cane toads, Bufo marinus, an invasive
      species of major concern in tropical Australia, produce species-specific chemical
      cues that alert conspecific tadpoles to danger. Repeated exposure to the alarm
      chemical reduces tadpole survival rates and body sizes at metamorphosis and,
      thus, could help control toad populations. To evaluate the feasibility of this
      approach, we need to know how the intensity of toad tadpole response to the alarm
      chemical is affected by factors such as water temperature, time of day, larval
      stage and feeding history, geographic origin of the tadpoles, and habituation.
      Information on these topics may enable us to optimize deployment, so that
      tadpoles encounter pheromone at the times and places that confer maximum effect.
      In our studies, tadpole density, nutritional state, larval stage, and geographic
      origin had little effect on the intensity of the alarm response, but tadpoles
      reacted most strongly in higher water temperatures and during daylight hours.
      Repeated, once-daily exposure to pheromone did not induce habituation, but
      repeated exposure at 15-min intervals did not elicit further responses after 2 h
      total exposure. The insensitivity of response to most factors tested means that
      the effectiveness of the pheromone as a control agent should be relatively
      robust.

PMID- 19184226
TI  - The yield of SPECT/CT for anatomical lymphatic mapping in patients with melanoma.
AB  - BACKGROUND: The hybrid single-photon emission computed tomography camera with
      integrated CT (SPECT/CT) fuses tomographic lymphoscintigrams with anatomical CT
      data. SPECT/CT shows the exact anatomical location of a sentinel node and may
      detect additional drainage. The purpose of this study was to explore its
      potential in patients with melanoma. METHODS: We studied 85 patients with
      melanoma with conventional lymphoscintigrams that were difficult to interpret (51
      patients), that showed an unusual drainage pattern (33 patients), or with
      nonvisualization (1 patient). Forty-one patients had melanoma on an extremity, 31
      on the trunk, and 14 in the head and neck region. SPECT/CT was performed
      following late conventional imaging without reinjection of the
      radiopharmaceutical. RESULTS: Conventional imaging suggested 214 sentinel nodes
      in 84 of the 85 patients (99%). SPECT/CT showed these same nodes and 12 extra
      sentinel nodes in seven patients (8%). Ten of these additional nodes were
      harvested, of which three nodes of two patients harbored metastases. There was a
      clear advantage of SPECT/CT in 30 patients (35%), resulting in a different
      incision in 17 patients, an incision at another site in 8, and an extra incision
      in 5 patients. The value was questionable in 19 patients (22%) in whom sentinel
      nodes were more clearly visualized by SPECT/CT, although the incision remained
      unchanged. There was no additional value of SPECT/CT in 36 patients (42%).
      CONCLUSIONS: SPECT/CT detects additional drainage and shows the exact anatomical
      location of sentinel nodes in patients with inconclusive conventional
      lymphoscintigrams. SPECT/CT facilitates surgical exploration in difficult cases
      and may improve staging.

PMID- 19184227
TI  - Men with breast cancer have same disease-specific and event-free survival as
      women.
AB  - BACKGROUND: Breast carcinoma in men is an uncommon disease. The aim of this study
      is to compare overall survival (OS) and disease-specific survival (DSS) in a
      group of matched men and women with breast cancer. METHODS: Each man with breast
      cancer recorded in the database was matched with two women. Matching was done
      based on age, year of diagnosis, and stage. To compare breast cancer
      characteristics between men and women, the chi-square test was used for
      qualitative data and the t-test for quantitative data. Overall survival and DSS
      were calculated using Kaplan-Meier methods. Cox proportional hazards models have
      been used to compare survival rates between men and women. RESULTS: The 58 male
      breast cancer patients were matched with 116 female patients. The mean age at
      diagnosis was 63.9 +/- 11.9 years for men and 65.7 +/- 11.5 years for women (P =
      .72). The median follow-up was 9.7 years for men and 10.7 years for women. The 5-
      and 10-year OS for men were, respectively, 58.9% and 33.9%. The 5- and 10-year OS
      for women were 68.2% and 52.1%. Men with breast cancer had a significant risk of
      dying compared with women (hazard ratio [HR] = 1.59; 95% confidence interval (95%
      CI), 1.04-2.42, P = .03). The 5- and 10-year DSS were 73.0% and 55.1% for men,
      and 72.8 and 61.2% for women, respectively. There was no difference in DSS
      between the two matched groups (HR = 1.26; 95% CI, 0.76-2.10, P = .37).
      CONCLUSIONS: The prognosis for men with breast carcinoma is similar to that for
      women with similar-stage disease.

PMID- 19184228
TI  - Stage IV breast cancer: is surgical resection of clinical utility?

PMID- 19184229
TI  - Gemicitabine resistence and mesenchymal phenotype.

PMID- 19184231
TI  - Predicting prognosis of gastric cancer: limitations of metastatic lymph nodes
      number and promise of genomics.

PMID- 19184232
TI  - Barrett's esophagus in the esophageal remnant: a critical long-term complication
      of subtotal esophagectomy.

PMID- 19184233
TI  - Is there a role for surgery in recurrent gastric cancer.

PMID- 19184234
TI  - Laparoscopic peritoneal cytology: can it affect decision-making for neoadjuvant
      treatment of gastric cancer?

PMID- 19184235
TI  - Challenges in developing robust genetic markers and targets to predict and
      prevent distant and peritoneal recurrence in gastric cancer.

PMID- 19184237
TI  - Pulmonary resection for colorectal cancer metastases: duration between cancer
      onset and lung metastasis as an important prognostic factor.
AB  - BACKGROUND: Pulmonary resection is the most effective treatment available for
      colorectal lung metastases. However, the characteristics of those patients most
      likely to benefit from surgical resection have not yet been adequately clarified.
      We have made a critical analysis for the potential prognostic factors and their
      clinical significance in lung metastasis from colorectal cancer. METHODS: We
      analyzed 63 consecutive patients who underwent curative pulmonary resection for
      colorectal lung metastases at National Taiwan University Hospital from January
      1997 to December 2006. Median follow-up was 37.3 (range 12-122) months. Disease
      free and overall survival rates were evaluated by Kaplan-Meier analysis, and
      multivariate analyses of various prognostic characteristics were performed.
      RESULTS: Overall 5-year survival and disease-free survival rates were 43.9% and
      19.5%, respectively. Multivariate analysis showed that the interval for
      development of lung metastases from primary colorectal cancer and the mode of
      operation were the only two independent prognostic factors for survival. With
      regard to disease-free survival, the interval between initial resection of
      colorectal cancer and following lung metastases was the only significant
      independent prognostic factor. Besides, subset analysis showed that the 5-year
      survival rate in repeated resection group for recurrence of colorectal metastasis
      in residual lung was 85.7%. CONCLUSION: Pulmonary resection, initial or even
      repeated resection for metastatic tumor from colorectal cancer should be
      encouraged for selected patients as it can significantly improve survival.
      Patients who have lung metastases within 1 year after primary tumor resection and
      those who do not undergo anatomical resection for metastatic lung tumor should be
      followed more carefully due to poor prognosis.

PMID- 19184236
TI  - Optimizing melphalan pharmacokinetics in regional melanoma therapy: does
      correcting for ideal body weight alter regional response or toxicity?
AB  - BACKGROUND: This study aims to determine what effect correcting melphalan dosing
      for ideal body weight (IBW) has on toxicity and response in isolated limb
      infusion (ILI) in patients with advanced extremity melanoma. METHODS: This was an
      open observational study examining whether correcting the melphalan dose for IBW
      will influence response and toxicity in patients undergoing ILI for advanced
      extremity melanoma in 41 patients undergoing 42 procedures (13 without correction
      for IBW; and 29 with correction for IBW). Melphalan pharmacokinetics, limb
      toxicity, serologic toxicity, and response at 3 months were compared. RESULTS:
      The corrected group had a lower estimated limb volume (V (esti)) to melphalan
      volume at steady state (V (ss)) (P < .0001) ratio as well as lower incidence of
      grade > or =3 regional toxicity, serologic toxicity, and compartment syndrome (P
      = .0249, P = .027, P = .02). There was a positive correlation of V (esti)/V (ss)
      to toxicity (P = .0127, r = .382). No significant difference in response (P =
      .3609) between the groups was found, although there was a trend of association
      between V (esti)/V (ss) and response (P = .051, r = .3383). CONCLUSIONS:
      Correcting for IBW in ILI lowers toxicity without significantly altering response
      rates.

PMID- 19184238
TI  - Endogenous NIS expression in triple-negative breast cancers.
AB  - BACKGROUND: The sodium iodide symporter (NIS) mediates iodide transport into
      cells and has been identified in approximately 70% of breast cancers. Functional
      NIS expression raises the possibility of using (131)I for therapeutic targeting
      of tumor cells. Treatment of triple-negative breast cancers
      [estrogen/progesterone receptor-negative and HER2-negative (ER-/PR-/HER2-)] is
      primarily limited to chemotherapy. Our aim was to characterize NIS expression in
      this subset of tumors. METHODS: Archival tissue sections from 23 women with
      triple-negative breast cancer were analyzed for NIS expression using
      immunohistochemical methods and an anti-human NIS antibody. Tumors were evaluated
      for the presence of plasma membrane immunoreactivity. One patient with a NIS
      expressing positive tumor underwent (123)I scintigraphic imaging with dosimetric
      analysis. RESULTS: Fifteen cases (65.2%) demonstrated NIS-positivity with 11
      tumors (47.8%) exhibiting strong expression. Plasma membrane immunoreactivity was
      observed in four breast cancers and was equivocal in another four tumors. Tumor
      specific radioiodide uptake was demonstrated by (123)I scintigraphy in a patient
      with a large primary breast cancer unresponsive to neoadjuvant therapy. The tumor
      concentrated 2.05, 1.53, and 1.96 times more isotope than normal breast tissue at
      1, 5, and 21 h. The relative increased uptake is consistent with positive NIS
      expression in the tumor on definitive surgery; however, the cumulative
      concentration in the tumor was not sufficient to achieve a therapeutic effect,
      had the isotope been (131)I. CONCLUSIONS: NIS is strongly expressed in a
      significant proportion of triple-negative breast cancer cells, suggesting a
      potential role for NIS-directed (131)I-radioablative strategies in this patient
      population.

PMID- 19184239
TI  - Differential gene expression analysis of subcutaneous fat, fascia, and skin
      overlying a Dupuytren's disease nodule in comparison to control tissue.
AB  - Dupuytren's disease (DD) is a benign fibroproliferative tumor with an unknown
      etiology and high recurrence postsurgery. Several observations suggest the
      possible involvement of skin overlying nodule (SON) and the subcutaneous fat in
      the pathogenesis of DD. This study aims to (1) compare the gene expression levels
      of SON and subcutaneous fat in DD and normal subjects and (2) to compare
      transverse palmar fascia (Skoog's fibers) from DD patients as internal control
      tissue, with palmar fascia (transverse carpal ligament) from patients undergoing
      carpal tunnel release as external control. Skin, fat, and fascia were obtained
      from five DD patients of Caucasian origin (age = 66 +/- 14) and from five control
      subjects (age = 57 +/- 19) undergoing carpal tunnel release. Total ribonucleic
      acids was extracted from each sample and used for complementary deoxyribonucleic
      acid synthesis. Real-time quantitative polymerase chain reaction was used to
      assess the gene expression levels of six candidate genes: A disintegrin and
      metalloproteinase domain (ADAM12), aldehyde dehydrogenase 1 family member A1
      (ALDH1A1), iroquois homeoboxprotein 6 (IRX6), periostin, osteoblast specific
      factor, proteoglycan 4, and tenascin C. Using independent t test, ADAM12,
      ALDH1A1, and IRX6 expression levels in DD fats were significantly (p < 0.05)
      higher than those in the controls. There is no significant difference in the gene
      expression levels of all six genes when comparing disease and control fascia and
      skin. Interestingly, ADAM12 up-regulation has also been observed in several other
      fibrotic and proliferative disorders. In conclusion, this study demonstrates
      potential roles for subcutaneous fat in DD pathogenesis as well as supports the
      use of transverse palmar fascia as appropriate control tissues in DD research.

PMID- 19184240
TI  - U.S. physicians' views on financing options to expand health insurance coverage:
      a national survey.
AB  - BACKGROUND: Physician opinion can influence the prospects for health care reform,
      yet there are few recent data on physician views on reform proposals or access to
      medical care in the United States. OBJECTIVE: To assess physician views on
      financing options for expanding health care coverage and on access to health
      care. DESIGN AND PARTICIPANTS: Nationally representative mail survey conducted
      between March 2007 and October 2007 of U.S. physicians engaged in direct patient
      care. MEASUREMENTS: Rated support for reform options including financial
      incentives to induce individuals to purchase health insurance and single-payer
      national health insurance; rated views of several dimensions of access to care.
      MAIN RESULTS: 1,675 of 3,300 physicians responded (50.8%). Only 9% of physicians
      preferred the current employer-based financing system. Forty-nine percent favored
      either tax incentives or penalties to encourage the purchase of medical
      insurance, and 42% preferred a government-run, taxpayer-financed single-payer
      national health insurance program. The majority of respondents believed that all
      Americans should receive needed medical care regardless of ability to pay (89%);
      33% believed that the uninsured currently have access to needed care. Nearly one
      fifth of respondents (19.3%) believed that even the insured lack access to needed
      care. Views about access were independently associated with support for single
      payer national health insurance. CONCLUSIONS: The vast majority of physicians
      surveyed supported a change in the health care financing system. While a
      plurality support the use of financial incentives, a substantial proportion
      support single payer national health insurance. These findings challenge the
      perception that fundamental restructuring of the U.S. health care financing
      system receives little acceptance by physicians.

PMID- 19184241
TI  - Medical record documentation of patients' hearing loss by physicians.
AB  - BACKGROUND: Anecdotal evidence suggests that hearing loss, even when sufficient
      to prevent full access to spoken communication, often is underreported by
      patients and not documented by physicians. No published studies have investigated
      this issue quantitatively. OBJECTIVE: To assess the documentation of hearing loss
      in comprehensive physician notes in cases where the patients are known to have
      substantial binaural loss. DESIGN: Electronic medical record (EMR) notes for 100
      consecutive patients with substantial binaural hearing loss were reviewed
      retrospectively at a large academic medical center. All records reviewed were
      created within 2 years before the patient's audiometry. Comprehensive physician
      notes containing the headings "History" and "Physical Exam" were examined for
      documentation of hearing loss and scored as: no mention of loss; finding of loss;
      or hearing reported as normal. PARTICIPANTS: Consecutive adult patients with
      substantial binaural hearing loss by audiometry who also had a comprehensive
      medical assessment in their electronic medical record created within 2 years
      before audiometry. RESULTS: Thirty-six percent of EMRs had no mention of hearing
      loss, 28% reported some loss, and 36% percent indicated that hearing was normal.
      CONCLUSIONS: Substantial hearing loss, sufficient to prevent effective
      communication in the medical setting, often is underdocumented in medical
      records.

PMID- 19184242
TI  - Update in geriatric medicine.

PMID- 19184243
TI  - Somatostatin limits intestinal ischemia-reperfusion injury in macaques via
      suppression of TLR4-NF-kappaB cytokine pathway.
AB  - OBJECTIVE: Intestinal ischemia-reperfusion (IIR)-induced gut injury remains a
      challenge for critically ill patients despite the oxidative stress theory that
      has been elaborated. This study aimed to test whether Toll-like receptor 4 (TLR4)
      is involved in gut injury during IIR and whether somatostatin (SST) affects TLR4
      nuclear factor-kappaB (NF-kappaB) cytokine pathway in the intestinal mucosa of
      macaques. DESIGN: Fifteen macaques were randomized into control, IIR, and SST +
      IIR groups. Pieces of isolated ileal epithelium from each animal were incubated
      with lipopolysaccharide (LPS), interferon-gamma, or SST. Expression of TLR4 and
      NF-kappaBp65 was evaluated by immunohistochemical staining, Western blot analysis
      and reverse transcription polymerase chain reaction. Cytokine levels were
      measured by ELISA. Radioimmunoassay was used to determine of SST levels.
      MEASUREMENTS AND MAIN RESULTS: Significant overexpression (IIR vs control) of
      ileal TLR4 (0.17 +/- 0.03 vs 0.05 +/- 0.02), NF-kappaBp65 (0.55 +/- 0.11 vs 0.15
      +/- 0.05), and TNF-alpha (213.2 +/- 29.2 vs 56.0 +/- 10.04) after IIR was greatly
      decreased (p < 0.05) by prophylactic use of SST (TLR4: 0.06 +/- 0.02; NF
      kappaBp65: 0.26 +/- 0.09; TNF-alpha: 97.1 +/- 32.3) in vivo. TLR4 expression in
      the ileal epithelium treated with LPS and SST (1,330 +/- 93) was significantly
      lower than that in the ileal epithelium treated with LPS alone (2,088 +/- 126) in
      vitro. SST levels in plasma (3.67 +/- 0.41 ng/ml) and ileal mucosa (1,402.3 +/-
      160 ng/mg protein) of the IIR group were significantly lower than those (6.09 +/-
      1.29 ng/ml, 2,234. 8 +/- 301.8 ng/mg protein) in the control group (p < 0.05).
      CONCLUSIONS: Endogenous SST is a crucial inhibitor of massive inflammatory injury
      in the intestinal mucosa via direct suppression of the TLR4-NF-kappaB cytokine
      pathway induced by LPS in ileal epithelium. IIR attacks caused shortages of
      endogenous SST in the plasma and intestinal mucosa of macaques in this study.
      Therefore, preventive supplements of SST may limit intestinal injury of macaques
      by IIR.

PMID- 19184244
TI  - Neuroma of the bile duct: a late complication after cholecystectomy.
AB  - INTRODUCTION: Extrahepatic biliary obstruction with a mass in the common bile
      duct and elevated CA 19-9 level is often due to cholangiocarcinoma. CASE REPORT:
      We present a case of a 71 year-old woman who presented with an extrahepatic
      biliary obstruction and a mass in the common bile duct 45 years after
      cholecystectomy. Pathologic analysis revealed a bile duct neuroma. We present the
      preoperative imaging, operative management, pathologic diagnosis, and literature
      review of this rare condition.

PMID- 19184245
TI  - The early use of PET-CT alters the management of patients with esophageal cancer.
AB  - INTRODUCTION: The routine use of positron emission tomography-computed tomography
      (PET-CT) in the staging of patients with esophageal carcinoma remains
      contentious, with conflicting reports of its benefit. In our unit, PET-CT has
      been used routinely in the staging of all patients considered for radical therapy
      (surgery or chemoradiotherapy). Our aim was to determine the frequency with which
      PET-CT influenced decision making in the management of patients with carcinoma of
      the esophagus or gastroesophageal junction. METHODS: CT, PET-CT, and outcome
      information were collected on 38 patients considered for radical therapy. Patient
      proformas, with and without PET-CT findings, were constructed and each
      independently reviewed in a randomized and blinded fashion by five
      multidisciplinary team members (three surgeons, two oncologists) and a treatment
      strategy determined. RESULTS: PET-CT changed the staging for ten patients (26%).
      This translated into a change in management decision for seven patients (18%).
      The concordance between individual management plans and treatment intent was 79%
      for CT (150 of 190 decisions) and it was 92% for PET-CT (175 of 190 decisions).
      Full concordance between multidisciplinary team members was 66% with CT staging
      and 74% with the addition of PET-CT. CONCLUSION: The use of PET-CT early in the
      staging algorithm for esophageal carcinoma altered the staging for a quarter of
      patients and the management for a fifth of patients, supporting its inclusion
      early in the staging algorithm.

PMID- 19184246
TI  - Applications and future directions in invertebrate and fish cell culture.

PMID- 19184247
TI  - Aneuploidy in immortalized human mesenchymal stem cells with non-random loss of
      chromosome 13 in culture.
AB  - Aneuploidy (an abnormal number of chromosomes) is commonly observed in most human
      cancer cells, highlighting the need to examine chromosomal instability in
      tumorigenesis. Previously, the immortalized human mesenchymal stem cell line
      UE6E7T-3 was shown to undergo a preferential loss of one copy of chromosome 13
      after prolonged culture. Here, the loss of chromosome 13 was found to be caused
      by chromosome missegregation during mitosis, which involved unequal segregation,
      exclusion of the misaligned chromosome 13 on the metaphase plate, and trapping of
      chromosome 13 in the midbody region, as observed by fluorescence in situ
      hybridization. Near-diploid aneuploidy, not tetraploidy, was the direct result.
      The loss of chromosome 13 was non-random, and was detected by analysis of
      microsatellites and single nucleotide polymorphism-based loss of heterozygosity
      (LOH). Of the five microsatellite loci on chromosome 13, four loci showed
      microsatellite instability at an early stage in culture, and LOH was apparent at
      a late stage in culture. These results suggest that the microsatellite mutations
      cause changes in centromere integrity provoking loss of this chromosome in the
      UE6E7T-3 cell line. Thus, these results support the use of this cell line as a
      useful model for understanding the mechanism of aneuploid formation in cell
      cultures.

PMID- 19184248
TI  - Applications and potential uses of fish gill cell lines: examples with RTgill-W1.
AB  - Gills are unique structures involved in respiration and osmoregulation in
      piscinids as well as in many aquatic invertebrates. The availability of the trout
      derived gill cell line, RTgill-W1, is beginning to make impacts in fish health
      and toxicology. These cells are available from the American Type Culture
      Collection as ATCC CRL 2523. The cells have an epithelioid morphology and form
      tight monolayer sheets that can be used for testing epithelial resistance. The
      cells can be grown in regular tissue culture surfaces or in transwell membranes
      in direct contact with water on their apical surfaces. The ability of RTgill-W1
      to withstand hypo- and hyper-osmotic conditions and their optimal growth capacity
      at room temperature, make these cells ideal sentinel models for in vitro aquatic
      toxicology as well as model systems to study fish gill function and gill
      diseases. RTgill-W1 support growth of paramyxoviruses and orthomyxoviruses like
      salmon anemia virus. RTgill-W1 also support growth of Neoparamoeba pemaquidensis,
      the causative agent of amoebic gill disease. The cells have been used to
      understand mechanisms of toxicity, ranking the potencies of toxicants, and
      evaluating the toxicity of environmental samples. These cells are also valuable
      for high throughput toxicogenomic and toxicoproteomic studies which are easier to
      achieve with cell lines than with whole organisms. RTgill-W1 cell line could
      become a valuable complement to whole animal studies and in some cases as gill
      replacements in aquatic toxicology.

PMID- 19184249
TI  - Animal cell cultures in microsporidial research: their general roles and their
      specific use for fish microsporidia.
AB  - The use of animal cell cultures as tools for studying the microsporidia of
      insects and mammals is briefly reviewed, along with an in depth review of the
      literature on using fish cell cultures to study the microsporidia of fish. Fish
      cell cultures have been used less often but have had some success. Very short
      term primary cultures have been used to show how microsporidia spores can
      modulate the activities of phagocytes. The most successful microsporidia/fish
      cell culture system has been relatively long-term primary cultures of salmonid
      leukocytes for culturing Nucleospora salmonis. Surprisingly, this system can also
      support the development of Enterocytozoon bienusi, which is of mammalian origin.
      Some modest success has been achieved in growing Pseudoloma neurophilia on
      several different fish cell lines. The eel cell line, EP-1, appears to be the
      only published example of any fish cell line being permanently infected with
      microsporidia, in this case Heterosporis anguillarum. These cell culture
      approaches promise to be valuable in understanding and treating microsporidia
      infections in fish, which are increasingly of economic importance.

PMID- 19184250
TI  - The effect of short-term, high glucose concentration on endothelial cells and
      leukocytes in a 3D in vitro human vascular tissue model.
AB  - Efforts to determine a link between diabetes and atherosclerosis have involved
      examining the effect of high glucose levels on the adhesion and migration of
      circulating leukocytes, mostly monocytes and T lymphocytes. Leukocyte
      differentiation and proliferation within the subendothelial space can also be
      investigated by the use of a 3D in vitro human vascular tissue model. This model
      was used to study the effect of short-term, high glucose concentration on certain
      cell behavior associated with the early stages of atherosclerosis. Samples were
      exposed to either a 30- or 5.6-mM glucose concentration for 9 h to represent
      either hyperglycemic or normoglycemic conditions, respectively. There was a
      significant increase in vascular cell adhesion molecule-1 expression on the
      endothelial cells exposed to a 30-mM compared to a 5.6-mM glucose concentration.
      There was no significant difference in either intercellular adhesion molecule-1
      or E-selectin expression on the endothelial cells exposed to a 30-mM compared to
      a 5.6-mM glucose concentration. After the endothelium was exposed to 30 mM
      glucose concentration, there was a 70% increase in the number of monocytes
      (CD14(+)) migrating across the endothelium and a 28% increase in the number of
      these monocytes differentiating into macrophages, compared to cell migration and
      differentiation across the endothelium exposed to 5.6 mM glucose concentration.
      Also, for the endothelium exposed to 30 mM glucose concentration, there were
      nearly 2.5 times more T lymphocytes that migrated across the endothelium, along
      with significant cell proliferation, compared to cell migration across the
      endothelium exposed to 5.6 mM glucose concentration.

PMID- 19184251
TI  - Choice of DMEM, formulated with or without pyruvate, plays an important role in
      assessing the in vitro cytotoxicity of oxidants and prooxidant nutraceuticals.
AB  - There is much interest in the positive health effects of nutraceuticals, in
      particular, polyphenols, which have both antioxidant and prooxidant
      characteristics. Pyruvate, a scavenger of hydrogen peroxide, is a component in
      some, but not in all, commercial formulations of cell culture media, Dulbecco's
      modified Eagle's medium in particular. This study showed that the cytotoxicities
      to human fibroblasts of hydrogen peroxide, tert-butyl hydroperoxide, and various
      prooxidant nutraceuticals were lessened in Dulbecco's modified Eagle's medium
      formulated with pyruvate, as compared to the same medium but formulated without
      pyruvate. Intracellular glutathione was unaffected in cells treated with hydrogen
      peroxide in Dulbecco's modified Eagle's medium formulated with pyruvate, as
      compared to medium formulated without pyruvate. In these studies, intracellular
      glutathione was analyzed in acid-soluble cell extracts by determining the
      oxidation of reduced glutathione by 5,5'-dithiobis(2-nitrobenzoic acid) to
      glutathione disulfide, with the formation of the yellow chromagen, 5-thio-2
      nitrobenzoic acid, measured spectrophotometrically at 412 nm and by the
      visualization of reduced glutathione in cells stained with the fluorescent dye,
      Cell Tracker Green 5-chloromethylfluorescein diacetate. A survey of various cell
      culture media, formulated with and without pyruvate, confirmed that the level of
      added hydrogen peroxide was greatly lessened in those media formulated with
      pyruvate. This study suggested that the pyruvate status of Dulbecco's modified
      Eagle's medium be specified in the experimental design, especially in studies
      involving oxidative stress.

PMID- 19184252
TI  - Macrophage cell lines use CD81 in cell growth regulation.
AB  - CD81 is an integral membrane protein belonging to the tetraspanin superfamily. It
      has two extracellular domains that interact with cell surface proteins and two
      intracellular tails that contribute to cellular processes. Although there are
      considerable data about how CD81 affects T- and B-cell function, not much is
      known about how it impacts macrophages. To address this, we established four cell
      lines from mouse bone marrow in the presence of macrophage colony-stimulating
      factor and transfection with SV40 large T antigen. Two were CD81(-/-) (ASD1 and
      ASD2) and two were CD81(+/-) (2ASD1.10 and 2BSD1.10). Cells were Mac-2-, PU.1-,
      and c-fms-positive and all the cell lines were phagocytic indicating that they
      were macrophage-like. In mixtures of the two cell types in tissue culture, CD81(
      /-) cells out competed CD81(+/-) cells with CD81-bearing cells being undetectable
      after 50 cell culture passages. Although cell divisions during log-phase growth
      were not significantly different between CD81(+/-) macrophage cells and CD81(-/-)
      macrophage cells, we found that CD81(-/-) macrophage cells reached a higher
      density at confluency than CD81(+/-) macrophage cells. CD81 transcript levels
      increased as cultures became confluent, but transcript levels of other
      tetraspanin-related molecules remained relatively constant. Transfection of CD81
      into ASD1 (CD81(-/-)) cells reduced the density of confluent cultures of
      transformants compared to cells transfected with vector alone. These data suggest
      that CD81 potentially plays a role in macrophage cell line growth regulation.

PMID- 19184253
TI  - Maintaining hepatocyte differentiation in vitro through co-culture with hepatic
      stellate cells.
AB  - Primary hepatocytes lose their differentiated functions rapidly when in culture.
      Our aim was to maintain the differentiated status of hepatocytes in vitro by
      means of vital hepatic stellate cells (HSCs), their soluble and particulate
      factors and lipid extracts. Hepatocytes were placed into collagen-coated culture
      dishes in the presence of HSCs at different ages of pre-culture, with or without
      direct cell to cell contacts, at different cell ratios and in monoculture with
      cellular HSC components in place of vital cells. Changes in morphology and
      enhancement of phosphoenolpyruvate carboxykinase (PCK) activity by glucagon were
      used to determine the differentiated status of hepatocytes in 2d-short-term
      culture. HSCs proved able to maintain the differentiated function of hepatocytes
      in co-culture either by direct cell contacts or via factors derived from HSC
      conditioned medium. In comparison, however, without cellular contact to
      hepatocytes five to ten times as many HSCs were necessary to increase the PCK
      activity to the same degree as in the presence of intercellular contacts. Whereas
      stimulation in the presence of HSC/hepatocyte contacts was independent of HSC
      culture age only quiescent, resting HSCs (precultured for 1-2 d) were able to
      stimulate hepatocytes significantly via soluble factors. Culturing of hepatocytes
      with a lipid extract or a particulate fraction from HSCs clearly displayed a very
      strong beneficial effect on enzyme activity and morphology. HSCs maintain
      hepatocyte function and structure through preferentially cell-bound signalling
      and transfer of lipids.

PMID- 19184255
TI  - Small-bowel volvulus in late pregnancy due to internal hernia after laparoscopic
      Roux-en-Y gastric bypass.
AB  - Internal hernias are a specific cause of acute abdominal pain and are a well
      known complication after laparoscopic Roux-en-Y gastric bypass for morbid
      obesity. Although internal hernias are a rare cause of intestinal obstruction,
      they may evolve towards serious complications, such as extensive bowel ischemia
      and gangrene, with the need for bowel resection and sometimes for a challenging
      reconstruction of intestinal continuity. The antecolic position of the Roux limb
      is associated with a decrease in the incidence of small-bowel obstruction and
      internal hernias. The best prevention of the formation of these hernias is
      probably by closure of potential mesenteric defects at the initial operation with
      a non-absorbable running suture. We present a patient in late pregnancy with a
      small-bowel volvulus following laparoscopic Roux-en-Y gastric bypass for morbid
      obesity and discuss the available literature. For a favorable obstetric and
      neonatal outcome, it is crucial not to delay surgical exploration and an
      emergency operation usually is mandatory.

PMID- 19184254
TI  - In vitro culture of Lambdina fiscellaria lugubrosa nucleopolyhedrovirus in
      heterologous cell lines.
AB  - Infections of two heterologous insect cell lines derived from Malacosoma disstria
      (Md108) and Choristoneura fumiferana (Cf70) by the Lambdina fiscellaria lugubrosa
      nucleopolyhedrovirus (LafiNPV-W) were characterized. Cytopathic effects
      characteristic of LafiNPV-W infection, including rounding of cells, nuclear
      hypertrophy, and occlusion body (OB) production, were observed in both cell
      lines. Budded virus titers were slightly higher in Md108 cells than Cf70 cells
      (5.8 x 10(7) versus 3.1 x 10(7) TCID(50) units mL(-1)). Viral replication
      kinetics and cytopathic effects induced by LafiNPV-W infection were very similar
      in both cell lines. Actin rearrangements and redistribution of heterochromatin
      and euchromatin were observed within 24 h post-inoculation (hpi), and large
      quantities of nucleocapsids and virions were observed by electron microscopy at
      48 hpi in both cell lines. Cf70 cultures produced OBs with numerous embedded
      virions, while OBs in Md108 cultures contained few virions or were empty with
      nucleocapsids packed in the nucleoplasm between OBs. In bioassays against second
      instar L. fiscellaria lugubrosa, OBs derived from LafiNPV-W-infected Md108 cells
      induced significantly lower levels of mortality than OBs derived from LafiNPV-W
      infected Cf70 cells or from infected L. fiscellaria fiscellaria larvae.

PMID- 19184256
TI  - Results of sleeve gastrectomy-data from a nationwide survey on bariatric surgery
      in Germany.
AB  - BACKGROUND: Beginning January 1, 2005, the status and outcomes of bariatric
      surgery were examined in Germany. Data are registered in cooperation with the An
      Institute of quality assurance in surgery at the Otto-von-Guericke-University
      Magdeburg. The objective of this study was to examine the morbidity and mortality
      rates secondary to sleeve gastrectomy (SG) in Germany since 2006. METHODS: Data
      collection occurred prospectively in an online data bank. All primary bariatric
      procedures performed were recorded as were all re-operations in patients that had
      already undergone a primary operation. Specific data compiled on the sleeve
      gastrectomy procedure were evaluated with a focus on operative details and
      complication rates. RESULTS: The total study cohort contains 3,122 patients. From
      January 2006 to December 2007, 144 sleeve gastrectomy procedures were performed
      in the 17 hospitals participating in the study. The mean body mass index (BMI) of
      all patients was 48.8 kg/m(2). The BMI of patients undergoing SG was 54.5
      kg/m(2). In total, 73.8% of the patients were female and 26.2% of the patients
      were male. There were no significant differences between patients undergoing SG.
      The general complication rate after SG was 14.1%, and the surgical complication
      rate was 9.4%. The postoperative mortality rate was 1.4%. CONCLUSIONS: The
      complication rate during the first 2 years after SG in Germany is similar to that
      published in the literature. In order to improve the quality of bariatric
      surgery, an evaluation of data from a German multicenter trial is necessary to
      evaluate the position of SG in the bariatric algorithm.

PMID- 19184257
TI  - Clubfoot: etiology and treatment Ignacio V. Ponseti, MD, 1914-.
AB  - This biographical sketch of Ignacio V. Ponseti, MD, corresponds to the historic
      text, The Classic: Congenital Club Foot: The Results of Treatment, available at
      DOI 10.1007/s11999-009-0720-2 and The Classic: Observations on Pathogenesis and
      Treatment of Congenital Clubfoot, available at DOI 10.1007/s11999-009-0721-1.

PMID- 19184258
TI  - Dural and intradural compression as a cause of clubfoot. NJ Giannestras MD CORR
      1953;1:28-32. Calcaneovalgus foot in the newborn and its relationship to
      developmental flatfoot. CF Ferciot MD CORR 1953;1:22-27.

PMID- 19184259
TI  - A 38-year-old man with left knee pain.

PMID- 19184260
TI  - Treatment and outcomes of pelvic malunions and nonunions: a systematic review.
AB  - Although acute management of pelvic fractures and their long-term functional
      outcome have been widely documented, important information regarding malunion and
      nonunion of these fractures is sparse. Despite their relative rarity, malunions
      and nonunions cause disabling symptoms and have major socioeconomic implications.
      We analyzed the factors predisposing a pelvic injury to develop
      malunion/nonunion, the clinical presentation of these complications, and the
      efficacy of the reported operative protocols in 437 malunions/nonunions of 25
      clinical studies. Treatment of these demanding complications appeared effective
      in the majority of the cases: overall union rates averaged 86.1%, pain relief as
      much as 93%, patient satisfaction 79%, and return to a preinjury level of
      activities 50%. Nevertheless, the patient should be informed about the incidence
      of perioperative complications, including neurologic injury (5.3%), symptomatic
      vein thrombosis (5.0%), pulmonary embolism (1.9%), and deep wound infection
      (1.6%). For a successful outcome, a thorough preoperative plan and methodical
      operative intervention are essential. In establishing effective evidence-based
      future clinical practice, the introduction of multicenter networks of pelvic
      trauma management appears a necessity. LEVEL OF EVIDENCE: Level IV, therapeutic
      study. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 19184261
TI  - Thigh pain in a 73-year-old man.

PMID- 19184262
TI  - Differentially loaded radiostereometric analysis to monitor fracture stiffness: a
      feasibility study.
AB  - Inability to accurately and objectively assess the mechanical properties of
      healing fractures in vivo hampers clinical fracture management and research. We
      describe a method to monitor fracture stiffness during healing in a clinical
      research setting by detecting changes in fracture displacement using
      radiostereometric analysis and simultaneously measuring applied axial loads. A
      method was developed for load application, positioning of the patient, and
      radiographic setup to establish the technique of differentially loaded
      radiostereometric analysis (DLRSA). A DLRSA examination consists of
      radiostereometric analysis radiographs taken without load (preload), under
      different increments of load, and without load (postload). Six patients with
      distal femur fractures had DLRSA examinations at 6, 12, 18, and 26 weeks
      postoperatively. The DLRSA method was feasible in a clinical setting. The method
      provides objective and quantifiable data for internally fixed fractures and may
      be used in clinical research as a tool to monitor the in vivo stiffness of
      healing femoral fractures managed with nonrigid internal fixation.

PMID- 19184263
TI  - What proportion of patients need extensive surgery after failure of the Ponseti
      technique for clubfoot?
AB  - In 1948, Professor Ignacio Ponseti began a nonoperative management form of
      treatment for severe talipes equinovarus. This method of manipulative treatment
      became attractive because long-term outcomes demonstrated the majority of feet
      were pain-free, plantigrade, and functioning at a high level of activity without
      evidence of degenerative arthrosis. We retrospectively reviewed the charts of 51
      children (31 boys and 20 girls; 72 feet) with idiopathic clubfeet deformity
      treated with the Ponseti method from January 5, 2002, to January 5, 2007. The
      median age at treatment was 2 weeks (95% confidence limit, 1-2 weeks); there was
      no difference in age at presentation between boys and girls. The minimum followup
      was 4 months (mean, 19.8 months; range, 4-48 months). A total of 288 casts were
      applied (mean, 5.5; standard deviation, 0.92). Successful treatment was defined
      as a plantigrade foot with a normal hindfoot, midfoot, and forefoot on clinical
      examination. Correction was achieved and maintained in 90% (65 of 72) of the
      feet; 10% (seven of 72) of the treated feet did not improve and needed subsequent
      surgery. There was no difference in the proportion of children who had tenotomy
      or previous treatment among those who presented with residual deformity or
      recurrence or had surgery. However, patients who tolerated bracing had lower
      recurrence rates and underwent less surgery. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 19184264
TI  - Open versus two forms of arthroscopic rotator cuff repair.
AB  - There have been technologic advances in the methods for repairing torn rotator
      cuffs. We compared the clinical and structural outcomes of three different forms
      of rotator cuff repair with up to 24 months' followup. We wished to assess how
      surgical technique affected clinical outcomes and see how these correlated to
      repair integrity. Three cohorts of patients had repair of a symptomatic rotator
      cuff tear using (1) an open technique (n = 49); (2) arthroscopic knotted (n =
      53); or (3) arthroscopic knotless (n = 57) by one surgeon. Standardized patient-
      and examiner-determined outcomes were obtained preoperatively and at 6 weeks, 3
      and 6 months, and 2 years postoperatively. Ultrasound studies were performed with
      a validated protocol at 6 months and 2 years postsurgery. Clinical outcomes were
      similar with the exception that the arthroscopic groups had, on average, 20%
      better American Shoulder and Elbow Surgeons scores than the open group at 6
      months and 2 years. Retear correlated with tear size and operation time and
      occurred more frequently after open repair (39%) than after arthroscopic knotted
      (25%) and arthroscopic knotless (16%) repair. An intact cuff on ultrasound
      corresponded to better results for supraspinatus strength, patient outcomes, and
      rotator cuff functional ability. LEVEL OF EVIDENCE: Level III, therapeutic study.
      See Guidelines for Authors for a complete description of levels of evidence.

PMID- 19184265
TI  - Factors influencing the stability of stems fixed with impaction graft in vitro.
AB  - Mechanical stability of the stem is believed to be an important factor in
      successful impaction grafting in revision THA. We asked whether particle size,
      femoral bone deficiencies, stem design, graft composition, and impaction
      technique influenced the initial stability of the stem in vitro using model
      femora and human bone particles. Bone particles made with a reciprocating blade
      type bone mill contained larger particles with a broader size distribution than
      those made by a rotating drum-type bone mill and had higher stiffness on
      compression testing. The stiffness on torsional testing decreased as the degree
      of proximal-medial segmental deficiencies increased. The stiffness and maximum
      torque in a stem with a rectangular cross section and wide anteroposterior
      surface were higher in torsional tests. Adding hydroxyapatite granules to the
      bone particles increased the torsional stability. To facilitate compact bone
      particles, we developed a spacer between the guidewire and modified femoral
      packers. This spacer facilitated compacting bone particles from the middle up to
      the proximal and the technique increased the amount of impacted bone particles at
      the middle of the stem and also improved the initial stability of the stem. Stem
      design and degree of deficiencies influenced stiffness in the torsional test and
      the addition of hydroxyapatite granules enhanced torsional stiffness.

PMID- 19184266
TI  - Overcommitment but not effort-reward imbalance relates to stress-induced
      coagulation changes in teachers.
AB  - BACKGROUND: Stress-related hypercoagulability might link job stress with
      atherosclerosis. PURPOSE: This paper aims to study whether overcommitment, effort
      reward imbalance, and the overcommitment by effort-reward imbalance interaction
      relate to an exaggerated procoagulant stress response. METHODS: We assessed job
      stress in 52 healthy teachers (49 +/- 8 years, 63% women) at study entry and,
      after a mean follow-up of 21 +/- 4 months, when they underwent an acute
      psychosocial stressor and had coagulation measures determined in plasma. In order
      to increase the reliability of job stress measures, entry and follow-up scores of
      overcommitment and of effort-reward imbalance were added up to total scores.
      RESULTS: During recovery from stress, elevated overcommitment correlated with D
      dimer increase and with smaller fibrinogen decrease. In contrast, overcommitment
      was not associated with coagulation changes from pre-stress to immediately post
      stress. Effort-reward imbalance and the interaction between overcommitment and
      effort-reward imbalance did not correlate with stress-induced changes in
      coagulation measures. CONCLUSIONS: Overcommitment predicted acute stress-induced
      hypercoagulability, particularly during the recovery period.

PMID- 19184267
TI  - Combining bone resorption markers and heel quantitative ultrasound to
      discriminate between fracture cases and controls.
AB  - SUMMARY: This nested case-control analysis of a Swiss ambulatory cohort of
      elderly women assessed the discriminatory power of urinary markers of bone
      resorption and heel quantitative ultrasound for non-vertebral fractures. The
      tests all discriminated between cases and controls, but combining the two
      strategies yielded no additional relevant information. INTRODUCTION: Data are
      limited regarding the combination of bone resorption markers and heel
      quantitative bone ultrasound (QUS) in the detection of women at risk for
      fracture. METHODS: In a nested case-control analysis, we studied 368 women (mean
      age 76.2 +/- 3.2 years), 195 with low-trauma non-vertebral fractures and 173
      without, matched for age, BMI, medical center, and follow-up duration, from a
      prospective study designed to predict fractures. Urinary total pyridinolines
      (PYD) and deoxypyridinolines (DPD) were measured by high performance liquid
      chromatography. All women underwent bone evaluations using Achilles+ and Sahara
      heel QUS. RESULTS: Areas under the receiver operating-characteristic curve (AUC)
      for discriminative models of the fracture group, with 95% confidence intervals,
      were 0.62 (0.56-0.68) and 0.59 (0.53-0.65) for PYD and DPD, and 0.64 (0.58-0.69)
      and 0.65 (0.59-0.71) for Achilles+ and Sahara QUS, respectively. The combination
      of resorption markers and QUS added no significant discriminatory information to
      either measurement alone with an AUC of 0.66 (0.60-0.71) for Achilles+ with PYD
      and 0.68 (0.62-0.73) for Sahara with PYD. CONCLUSIONS: Urinary bone resorption
      markers and QUS are equally discriminatory between non-vertebral fracture
      patients and controls. However, the combination of bone resorption markers and
      QUS is not better than either test used alone.

PMID- 19184268
TI  - "Pathologic" fractures: should these be included in epidemiologic studies of
      osteoporotic fractures?
AB  - Pathologic fractures are often excluded in epidemiologic studies of osteoporosis.
      Using Medicare administrative data, we identified persons with vertebral and hip
      fractures. Among these, 48% (vertebral) and 3% (hip) of the fractures were coded
      as pathologic. Only 25% and 66% of persons with these pathologic fractures had
      evidence for malignancy. INTRODUCTION: Analyses of osteoporosis-related fractures
      that use administrative data often exclude pathologic fractures (ICD-9 733.1x)
      due to concern that these are caused by cancer. We examined "pathologic"
      fractures of the vertebrae and hip to evaluate their contribution to fracture
      incidence and assessed the evidence for a malignancy. METHODS: We studied US
      Medicare beneficiaries age > or =65 with new fractures identified using ICD-9
      diagnosis codes 733.13 (pathologic vert), 805.0, 805.2, 805.4, 805.8
      (nonpathologic vert); and 733.14 (pathologic hip), 820.0, 820.2, 820.8
      (nonpathologic hip). We further examined the proportion of cases with a diagnosis
      of a malignancy proximate to the fracture. RESULTS: We identified 44,120
      individuals with a vertebral fracture and 60,354 with a hip fracture.
      Approximately 48% of vertebral fractures and 3% of hip fractures were coded as
      pathologic. For only approximately 25% of persons with a "pathologic" vertebral
      fracture ICD-9 code, but 66% of persons with a "pathologic" hip fracture, there
      was evidence of a possible cancer diagnosis. CONCLUSION: Among US Medicare
      beneficiaries, one fourth of pathologic vertebral fracture and two thirds of
      pathologic hip fracture cases had evidence for a malignancy. Particularly for
      vertebral fractures, excluding persons with pathologic fractures in epidemiologic
      analyses that utilize administrative claims data substantially underestimates the
      burden of fractures due to osteoporosis.

PMID- 19184269
TI  - Spatial temporal modeling of hospitalizations for fall-related hip fractures in
      older people.
AB  - The study determined the spatial temporal characteristics of fall-related hip
      fractures in the elderly using routinely collected injury hospitalization and
      sociodemographic data. There was significant spatial temporal variation in
      hospitalized hip fracture rates in New South Wales, Australia. INTRODUCTION: The
      study determined the spatial temporal characteristics of fall-related hip
      fractures in the elderly using routinely collected injury hospitalization data.
      METHODS: All New South Wales (NSW), Australia residents aged 65+ years who were
      hospitalized for a fall-related hip fracture between 1 July 1998 and 30 June 2004
      were included. Bayesian Poisson regression was used to model rates in local
      government areas (LGAs), allowing for the incorporation of spatial, temporal, and
      covariate effects. RESULTS: Hip fracture rates were significantly decreasing in
      one LGA, and there were no significant increases in any LGAs. The proportion of
      the population in residential aged care facilities was significantly associated
      with the rate of hospitalized hip fractures with a relative risk (RR) of 1.003
      (95% credible interval 1.002, 1.004). Socioeconomic status was also related to
      hospitalized hip fractures with those in the third and fourth quintiles being at
      decreased risk of hip fracture compared to those in the least disadvantaged
      (fifth) quintile [RR = 0.837 (0.717, 0.972) and RR = 0.855 (0.743, 0.989)
      respectively]. CONCLUSIONS: There was significant spatial temporal variation in
      hospitalized hip fracture rates in NSW, Australia. The use of Bayesian methods
      was crucial to allow for spatial correlation, covariate effects, and LGA boundary
      changes.

PMID- 19184270
TI  - Glucocorticoid and cyclosporine refractory adult onset Still's disease
      successfully treated with tocilizumab.
AB  - We report a 29-year-old Japanese woman with disseminated intravascular
      coagulation (DIC) and adult onset Still's disease (AOSD). Her disease was
      refractory to high-dose glucocorticoids, two courses of steroid pulse therapy,
      and addition of cyclosporine (3.5 mg/kg/day). The serum interleukin-6 level was
      markedly elevated. Therefore, we administered an anti-interleukin-6 receptor
      antibody (tocilizumab, 8 mg/kg fortnightly), which dramatically improved her
      symptoms and the levels of acute-phase proteins. In addition, rapid tapering of
      the glucocorticoid dose was possible. Four months later, she was maintained on
      tocilizumab infusion once a month with low-dose steroid therapy. Cyclosporine is
      one of the first-line immunosuppressants for AOSD, especially when associated
      with DIC, hepatic failure, or hemophagocytic syndrome. In patients with
      cyclosporine-resistant AOSD, tocilizumab may be another useful option.

PMID- 19184271
TI  - Renal cell carcinoma and arterial hypertension.
AB  - BACKGROUND: The association between renal cell carcinoma and arterial
      hypertension has been the subject of various studies. These studies have not been
      consistent in clarifying the relationship between the two. Some authors contend
      that arterial hypertension is a consequence of renal cell carcinoma, which
      secretes vasoactive peptides. Others claim that arterial hypertension is a risk
      factor for the development of renal cell carcinoma. The purpose of our study is
      to assess if there is a direct connection between arterial hypertension and renal
      cell carcinoma. METHODS: Out of 16,755 patients who were examined by
      ultrasonography, 40 were diagnosed with renal tumors. Of the 40 patients, 29 had
      malignant renal tumors, and 11 had benign renal tumors. These diagnoses were
      confirmed by CT scan, renal biopsy, and histology. Most of the patients with
      renal cell carcinoma (79.3%) had arterial hypertension. The group with benign
      renal tumors served as a control group. Out of the 29 patients with malignant
      renal cell carcinoma, 24 patients were treated with total nephrectomy, one had a
      partial nephrectomy, and four patients were too unwell for surgical intervention.
      In the group of those with benign renal tumors, seven patients had partial
      nephrectomies for the removal of angiomyolipomas. The personal histories were
      taken at the initiation of the study, and vital signs were obtained before and
      after surgery. Statistical analyses were performed using the Statistical Package
      for Social Sciences, version 10.0. RESULTS: In the malignant group, the systolic
      blood pressure (SBP) before surgery was 157.41 +/- 27.86 mmHg, and the diastolic
      blood pressure (DBP) was 97.24 +/- 15.33 mmHg, while in the benign group, SBP was
      134.55 +/- 17.53 mmHg, and DBP was 88.18 +/- 14.01 mmHg. In the malignant group
      in those who had undergone nephrectomies, the mean systolic pressure was 136.82,
      and the diastolic pressure was 85.90. In the benign group, the systolic and
      diastolic blood pressures were normal before and after surgery. CONCLUSION: In
      the group of patients with both renal cell carcinoma and arterial hypertension,
      their hypertension was resolved after they underwent nephrectomies. In
      conclusion, our data suggest that renal cell carcinomas may cause arterial
      hypertension.

PMID- 19184272
TI  - The message for World Kidney Day 2009: hypertension and kidney disease-a marriage
      that should be prevented.

PMID- 19184273
TI  - A new diterpenoid and a new triterpenoid glucosyl ester from the leaves of
      Callicarpa japonica Thunb. var. luxurians Rehd.
AB  - A new abietane-type diterpenoid and a new oleanane-type triterpenoid glucosyl
      ester were isolated from the leaves of Callicarpa japonica Thunb. var. luxurians
      Rehd. (Verbenaceae) along with 11 known compounds, comprising seven
      triterpenoids, two sterols, a flavonoid, and an aliphatic glycoside. Their
      chemical structures were determined on the basis of spectroscopic data.

PMID- 19184274
TI  - Two new neolignan glycosides from leaves of Osmanthus heterophyllus.
AB  - Two new neolignan glycosides, (7R, 8R)-threo-guaiacylglycerol-8-O-4'-sinapyl
      ether 7-O-beta-D: -glucopyranoside (1) and (7S, 8R)-5-methoxydehydrodiconiferyl
      alcohol 4-O-beta-D: -glucopyranoside (2), and four known ones (3-6), were
      isolated from the leaves of Osmanthus heterophyllus. The structures of compounds
      1-6 were established on the basis of spectral and chemical data.

PMID- 19184275
TI  - A new flavonol galloylrhamnoside and a new lignan glucoside from the leaves of
      Koelreuteria henryi Dummer.
AB  - A new flavonol galloylrhamnoside, kaempferol 3-O-(2'',3''-di-O-galloyl)-alpha-L: 
      rhamnopyranoside, and a new lignan glycoside, hinokinin 7-O-beta-D: 
      glucopyranoside were isolated from the leaves of Koelreuteria henryi, along with
      18 known compounds, including six flavonol glycosides (3-8), three lignans (9
      11), four chlorophyll derivatives (12-15), two steroids (16, 17), and three
      aromatic compounds (18-20). The structures were determined on the basis of
      spectral analysis and chemical evidence. The scavenging effect of 1-8 and 20 on
      the stable free radical 1,1-diphenyl-2-picrylhydrazyl was examined. Compounds 1,
      5, 6, and 20 showed more potent activity than that of trolox.

PMID- 19184276
TI  - Five new glycosides from Hypericum erectum Thunb.
AB  - Five new glycosides, quercetin 3'-O-beta-D: -galactopyranoside (1), quercetin 3-O
      (2''-acetyl)-beta-D: -glucopyranoside (2), 4,6-dihydroxy-2-methoxyphenyl 1-O-beta
      D: -glucopyranoside (3), 4-hydroxy-2,6-dimethoxyphenyl 1-O-alpha-L: 
      rhamnopyranosyl (1 --> 6)-beta-D: -glucopyranoside (4) and 3-methyl-but-2-en-1-yl
      beta-D: -glucopyranosyl (1 --> 6)-beta-D: -glucopyranoside (5), were isolated
      from Hypericum erectum Thunb. Their structures were established on the basis of
      spectral and chemical data.

PMID- 19184277
TI  - Cross-reaction of antibody against Helicobacter pylori urease B with platelet
      glycoprotein IIIa and its significance in the pathogenesis of immune
      thrombocytopenic purpura.
AB  - Many clinical investigations have suggested that Helicobacter pylori (H. pylori)
      infection might be associated with immune thrombocytopenic purpura (ITP), but its
      role in the pathogenesis of ITP is unsettled. In this study, we cultured H.
      pylori, produced recombinant H. pylori urease (ure) B, and then prepared
      monoclonal antibody (MoAb) against ureB, 1F11, both 1F11 and MoAb against human
      platelet glycoprotein (GP) IIIa, SZ21, could bind to the band of GP IIIa of
      normal platelet lysate, but not to that from a patient with Glanzmann
      thrombasthenia (GT) whose GP IIb-IIIa complex was absent. Flow cytometry showed
      that normal platelets were reacted with 1F11 and SZ21, while GT platelets were
      not. In immuno-radiometric assay, the binding of (125)I-labeled 1F11 to GP IIIa
      was higher than that to GP Ib, GP IIb, GP VI, and P-selectin. 1F11 could partly
      compete with SZ21 in a binding to platelet surface. In addition, 1F11 inhibited
      platelet aggregation induced by adenosine diphosphate, but had no effect on
      platelet P-selectin expression or Thromboxane B(2) production of platelets. These
      results indicate that H. pylori ureB antibody could cross-react with human
      platelet GP IIIa and partly inhibit platelet aggregation. UreB may be a crucial
      component of H. pylori involved in the pathogenesis of a subset of ITP.

PMID- 19184278
TI  - Biphasic metaplastic sarcomatoid carcinoma of the breast: report of a case.
AB  - A 69-year-old woman was admitted to our hospital with the complaint of a right
      breast mass. As a result of thorough examinations, she was diagnosed with breast
      cancer and underwent breast-conserving surgery. The pathological findings of the
      resected specimen showed that the tumor consisted of intermingled carcinomatous
      and sarcomatous components with a transition zone. On immunohistochemical study,
      the sarcomatous cells in this transition zone showed partial positive staining
      for CD10, the myoepithelial marker, suggesting that the myoepithelial cells had
      transformed into sarcoma, and then this biphasic tumor was formed. Finally, she
      was diagnosed with biphasic metaplastic sarcomatoid carcinoma of the breast.
      Biphasic metaplastic sarcomatoid carcinoma of the breast is a relatively rare but
      aggressive disease. The pathological diagnosis is often controversial, requiring
      detailed immunohistochemical analysis. We report our experience with a case of
      biphasic metaplastic sarcomatoid carcinoma of the breast.

PMID- 19184279
TI  - Breast cancer with cartilaginous and/or osseous metaplasia.
AB  - We report a rare case of breast cancer with cartilaginous and/or osseous
      metaplasia. A 59-year-old woman had a large lump in her left breast, which had
      enlarged gradually over a period of 2 years. Mammography, ultrasonography and
      aspiration cytology suggested phyllodes tumor with carcinoma. She underwent wide
      excision and sentinel lymph node biopsy. Because of the existence metastatic
      tumor cells in the sentinel lymph node on frozen section, sequential axillary
      lymph node dissection was conducted consequently. Histologically, the tumor
      consisted of invasive ductal carcinoma and spindle-cell carcinoma, including
      cartilaginous metaplasia. Adjuvant chemotherapy and whole-breast irradiation were
      performed. However, she died of multiple metastases to the liver 2 years after
      surgery. Breast cancer with cartilaginous and/or osseous metaplasia belongs to a
      special type of invasive carcinoma, and the incidence is very low. We here
      present our case and a review of the literature.

PMID- 19184280
TI  - Clinical application of artificial bone in the maxillofacial region.
AB  - Hard tissue reconstruction is very useful for bony defects of the maxillofacial
      region. Autogenous bone, allogeneic bone, and artificial bone have been used to
      reconstruct maxillofacial bone; however, the use of autogenous bone involves high
      surgical invasiveness because of the need to harvest the bone. The use of
      allogeneic bone is associated with infections, raises ethical concerns, and is
      not widely used in Japan. Artificial bone has several advantages, including no
      need for bone harvesting, excellent biocompatibility, and a relatively easy
      surgical procedure. Use of artificial bone avoids the much greater invasiveness
      of harvesting bone, and several types of artificial bone have been developed.
      Design requirements for artificial bone include surgical manipulability,
      structural compatibility with the defective area, support properties, and the
      ability to induce bone regeneration; however, no artificial bone meeting all
      these requirements has yet been developed. Artificial bone is used in many
      patients in our medical center, and we have been active in developing the next
      generation of artificial bone with better properties. In this article, we present
      a case history and discuss the future development of artificial bone for use in
      maxillofacial reconstruction.

PMID- 19184281
TI  - Polymeric membrane materials for artificial organs.
AB  - Many polymeric materials have already been used in the field of artificial
      organs. However, the materials used in artificial organs are not necessarily
      created with the best material selectivity and materials design; therefore, the
      development of synthesized polymeric membrane materials for artificial organs
      based on well-defined designs is required. The approaches to the development of
      biocompatible polymeric materials fall into three categories: (1) control of
      physicochemical characteristics on material surfaces, (2) modification of
      material surfaces using biomolecules, and (3) construction of biomimetic membrane
      surfaces. This review will describe current issues regarding polymeric membrane
      materials for use in artificial organs.

PMID- 19184282
TI  - Development of a compact wearable pneumatic drive unit for a ventricular assist
      device.
AB  - The purpose of this study was to develop a compact wearable pneumatic drive unit
      for a ventricular assist device (VAD). This newly developed drive unit, 20 x 8.5
      x 20 cm in size and weighing approximately 1.8 kg, consists of a brushless DC
      motor, noncircular gears, a crankshaft, a cylinder-piston, and air pressure
      regulation valves. The driving air pressure is generated by the reciprocating
      motion of the piston and is controlled by the air pressure regulation valves. The
      systolic ratio is determined by the noncircular gears, and so is fixed for a
      given configuration. As a result of an overflow-type mock circulation test, a
      drive unit with a 44% systolic ratio connected to a Toyobo VAD blood pump with a
      70-ml stroke volume achieved a pump output of more than 7 l/min at 100 bpm
      against a 120 mmHg afterload. Long-term animal tests were also performed using
      drive units with systolic ratios of 45% and 53% in two Holstein calves weighing
      62 kg and 74 kg; the tests were terminated on days 30 and 39, respectively,
      without any malfunction. The mean aortic pressure, bypass flow, and power
      consumption for the first calf were maintained at 90 x 13 mmHg, 3.9 x 0.9 l/min,
      and 12 x 1 W, and those for the second calf were maintained at 88 x 13 mmHg, 5.0
      x 0.5 l/min, and 16 x 2 W, respectively. These results indicate that the newly
      developed drive unit may be used as a wearable pneumatic drive unit for the
      Toyobo VAD blood pump.

PMID- 19184283
TI  - A nonpulsatile total artificial heart with 1/R control.
AB  - A total artificial heart (TAH) using continuous flow pumps is promising for size
      reduction of the device; however, the role of pulsatility in TAHs has been a
      subject of great debate. Additionally, it is unclear whether, in a nonpulsatile
      TAH, a physiological control method such as 1/R control can keep the experimental
      animal in good condition. To realize a nonpulsatile TAH with 1/R control, the
      artificial valves were removed from undulation pump total artificial hearts
      (UPTAHs), which can produce both pulsatile and nonpulsatile flows using a single
      device. The UPTAHs were implanted into 18 goats, and 4 goats survived for more
      than 1 month. Three weeks of long-term nonpulsatile TAH operation could be tested
      in the goat that survived for 72 days, and it was proved that 1/R control is
      possible not only with a pulsatile TAH but also with a nonpulsatile TAH. The
      general condition of the goat and its organ function did not change on the
      application of nonpulsatile mode. Cardiac output and arterial pressure changed
      with the condition of the goat in pulsatile and also in nonpulsatile modes, and
      the changes seemed almost identical. However, the sucking effect of the atria was
      very significant in nonpulsatile mode, resulting in hemolysis. Therefore,
      nonpulsatile TAHs under 1/R control are considered to be inadequate unless some
      pulsatility can be introduced to avoid fatal sucking effects and to ensure
      sufficient inflow. During nonpulsatile operation, regular fluctuations were
      sometimes found in the aortic pressure, and these were caused by the periodic
      sucking effect in the left atrium that was possibly influenced by respiratory
      changes.

PMID- 19184284
TI  - Frequency analysis of high-intensity transient signals of transcranial Doppler
      ultrasound in patients supported with a left ventricular assist device.
AB  - Left ventricular assist devices (LVADs) have become more important than ever for
      patients with terminal heart disease. The chronic shortage of donors for heart
      transplantation may enhance the importance of LVADs as destination therapy. To
      prevent cerebral complications, the evaluation of high-intensity transient
      signals (HITS) of transcranial Doppler (TCD) ultrasound is important. In the
      present study, HITS were measured on seven occasions in patients supported with
      LVADs. The high-frequency counts in HITS were greater than the low-frequency
      counts (47 +/- 42 vs. 9 +/- 9 in 3 min, P = 0.025), and declined further with
      oxygen delivery to the patient. The high frequency of signals may imply air
      microemboli, and the counts may increase with time.

PMID- 19184285
TI  - Safety evaluation of surgical materials by cytotoxicity testing.
AB  - The cytotoxicity of three kinds of commercially available absorbable hemostats
      [oxidized cellulose (Surgicel, gauze and cotton types), microfibrillar collagen
      (Avitene), and cotton-type collagen (Integran)] and one adhesion barrier [sodium
      hyaluronate and carboxymethyl-cellulose membrane (Seprafilm)] were comparatively
      assessed by a colony assay using V79 cells and a minimum essential medium (MEM)
      elution assay in combination with a neutral red assay using L929 cells. Strong
      cytotoxicity was detected for Surgicel by both the MEM elution assay and the
      colony assay. For Avitene, both methods revealed weak cytotoxicity. For
      Seprafilm, no cytotoxicity was detected by the MEM elution assay, while a
      moderate degree of cytotoxicity was observed in the colony assay. For Integran
      cytotoxicity was not detected by either the MEM elution or the colony assay. The
      results of the different methods showed some inconsistency in terms of the degree
      of cytotoxicity of the materials. It is proposed that the combination of two or
      more sensitive cytotoxicity testing methods for the evaluation of biomaterials is
      necessary to avoid false-negative results for biomaterials at the preclinical
      stage. Furthermore, investigation of the correlation between the cytotoxicity and
      the extraction period of the surgical materials is helpful for predicting the
      effect of prolonged in vivo use of biomaterials on surrounding cells, tissues,
      and organs.

PMID- 19184286
TI  - Influence of blood corpuscles on the ultrafiltration of various proteins.
AB  - The ultrafiltration characteristics of a commercial dialyzer were examined by
      measuring the sieving coefficient (s.c.) for three proteins, i.e., cytochrome c,
      chymotrypsinogen, and albumin, in a bovine blood system. Test blood was passed
      through a filter at a blood flow rate of 200 ml/min and filtrate was collected at
      an ultrafiltration flow rate of 10 ml/min from a port located near the blood
      inlet. The s.c. for cytochrome c and chymotrypsinogen in bovine blood sharply
      increased at the beginning of the experiment and reached a steady value that was
      about 60% of that obtained in an aqueous solution system. This may have been
      caused by the masking effect of the erythrocytes. The s.c. for albumin at steady
      state in bovine blood that contained added albumin only was almost the same as
      that obtained in the aqueous solution system. When all three proteins were added
      to bovine blood, however, the s.c. for albumin showed a steady value (after a
      slight decrease at the beginning of the experiment) the absolute value of which
      was higher than that found in the aqueous solution system. This phenomenon may
      have been caused by the stirring effect of erythrocytes that would disturb the
      concentration polarization of albumin formed near the membrane.

PMID- 19184287
TI  - Application of cultured dermal substitute for amelioration of maxillary bone
      growth suppression after cleft palate operation in rats.
AB  - The growth and development of maxillary bone and dentition is often impaired in
      patients who have undergone the cleft palate operation (push back method). Wound
      contraction exerts adverse effects on maxillary bone growth. The present study
      investigates the ability of cultured dermal substitute (CDS) to ameliorate
      maxillary bone growth suppression in experimental animals. We prepared CDS by
      incorporating rat fibroblasts into a matrix comprising a spongy hyaluronic acid
      (HA) sheet combined with collagen gel. The number of fibroblasts in the CDS was
      adjusted to 1.0 x 10(5) cells/cm(2). Wistar rats were randomly assigned to one of
      the following groups: I, control (no operation); II, surgically exposed bone
      without matrix or CDS; III, surgery with matrix; IV, surgery with CDS. Under
      pentobarbital anesthesia, about 2 x 4 mm of the mucosa and periosteum was
      surgically removed from the left half of the palate. A silicone sheet was placed
      on the matrix or CDS and affixed with superglue. The palatal width was measured 9
      weeks later in skull preparations as the distance between the cheek side cusps of
      the second molar. The palates in group IV were significantly wider than those in
      groups II and III, and did not significantly differ from that in the control
      group. These findings indicated that CDS has the ability to promote wound healing
      and reduce scar formation through the synergic effects of fibroblasts and the
      matrix, and thereby to ameliorate indirectly the growth of maxillary bone.

PMID- 19184288
TI  - Comparative evaluation of re-epithelialization promoted by fresh or cryopreserved
      cultured dermal substitute.
AB  - Allogeneic cultured dermal substitute (CDS) was prepared by plating cultured
      fibroblasts on a two-layered spongy matrix of hyaluronic acid and atelocollagen,
      followed by culturing for 1 week. The resulting fresh CDS was then cryopreserved
      in a freezer at -152 degrees C in accordance with conventional procedures. Fresh
      CDS was rinsed thoroughly with lactated Ringer's solution to remove fetal bovine
      serum (FBS) and was then used in the clinical study, whereas cryopreserved CDS
      was thawed and then rinsed with lactated Ringer's solution to remove
      cryoprotectant and FBS. The present study was designed to compare the efficacy of
      fresh and cryopreserved CDS in promoting reepithelialization at donor sites
      leaving behind split-thickness skin autografts. Fourteen donor sites were used
      for this comparative study. There were no differences in the period of complete
      re-epithelialization between the fresh and cryopreserved CDS. The results of this
      comparative study thus suggest that cryopreserved CDS is able to maintain the
      same level of potency to promote re-epithelialization as fresh CDS. This
      indicates that, although the release of growth factors is suppressed to some
      extent during the course of cryopreserving, thawing, and rinsing procedures, it
      is still sufficient to promote re-epithelialization.

PMID- 19184289
TI  - Standardization for mass production of allogeneic cultured dermal substitute by
      measuring the amount of VEGF, bFGF, HGF, TGF-beta, and IL-8.
AB  - Fibroblasts were isolated from a piece of donated skin measuring about 1 x 1 cm
      and were proliferated over nine successive cultivations. Fibroblasts obtained
      from the fourth cultivation were cryopreserved in 10 cryotubes as master cells.
      Fibroblasts obtained from the fifth to ninth cultivations were cryopreserved in
      49 cryotubes in total as working cells. At the end of each procedure in the
      fourth to eighth cultivations, about three-quarters of the proliferated
      fibroblasts were cryopreserved, and the remaining one-quarter were proliferated
      in the next cultivation. All fibroblasts obtained from the ninth (final)
      procedure were cryopreserved as the last working cells. Two cryotubes of the last
      cryopreserved working cells (ninth cultivation) were thawed and proliferated.
      Cultured dermal substitute (CDS) was prepared by performing ten successive
      cultivations. After each cultivation, about three-quarters of the resulting
      fibroblasts were used to prepare CDS, and the remaining one-quarter were
      proliferated in the next cultivation for 1 week. Finally, all fibroblasts
      produced by the tenth (final) procedure were used to prepare CDS. In each of the
      first to ninth cultivations for CDS preparation, the density of fibroblasts
      remained relatively constant, and the levels of cytokines, i.e., vascular
      endothelial growth factor, basic fibroblast growth factor, hepatocyte growth
      factor, transforming growth factor-beta 1, and interleukin-8 released from CDS
      remained relatively constant. In total, 47 sheets of CDS measuring 10 x 10 cm
      were prepared. The present findings indicate that about 1000 sheets of CDS
      measuring 10 x 10 cm can be prepared using all the working cells prepared from a
      piece of donated skin measuring 1 x 1 cm.

PMID- 19184290
TI  - Pivot wear of a centrifugal blood pump developed for circulatory assist.
AB  - We are developing a monopivot centrifugal pump for circulatory assist for a
      period of more than 2 weeks. The impeller is supported by a pivot bearing at one
      end and by a passive magnetic bearing at the other. The pivot undergoes
      concentrated exposure to the phenomena of wear, hemolysis, and thrombus
      formation. The pivot durability, especially regarding the combination of
      male/female pivot radii, was examined through rotating wear tests and animal
      tests. As a result, combinations of similar radii for the male/female pivots were
      found to provide improved pump durability. In the extreme case, the no-gap
      combination would result in no thrombus formation.

PMID- 19184291
TI  - Improvement in magnetic field immunity of externally-coupled transcutaneous
      energy transmission system for a totally implantable artificial heart.
AB  - Transcutaneous energy transmission (TET) that uses electromagnetic induction
      between the external and internal coils of a transformer is the most promising
      method to supply driving energy to a totally implantable artificial heart without
      invasion. Induction-heating (IH) cookers generate magnetic flux, and if a cooker
      is operated near a transcutaneous transformer, the magnetic flux generated will
      link with the external and internal coils of the transcutaneous transformer. This
      will affect the performance of the TET and the artificial heart system. Hence, it
      is necessary to improve the magnetic field immunity of the TET system. During
      operation of the system, if the transcutaneous transformer is in close proximity
      to an IH cooker, the electric power generated by the cooker and coupled to the
      transformer can drive the artificial heart system. To prevent this coupling, the
      external coil was shielded with a conductive shield that had a slit in it. This
      reduces the coupling between the transformer and the magnetic field generated by
      the induction cooker. However, the temperature of the shield increased due to
      heating by eddy currents. The temperature of the shield can be reduced by
      separating the IH cooker and the shield.

PMID- 19184292
TI  - Molecular mechanisms of taste transduction in vertebrates.
AB  - Among the five senses, taste and olfaction play crucial roles in the detection of
      chemical substances in the environment and are referred to as chemical senses. In
      the past decade, much progress has been made in studies on molecular mechanisms
      of the gustatory system by methods such as those based on molecular and cellular
      biology, genetics, and bioinformatics. This review covers recent studies on taste
      receptors, intracellular signaling transduction in taste receptor cells, and
      taste coding at the periphery in vertebrates from fish to mammals.

PMID- 19184293
TI  - Dental occlusion: modern concepts and their application in implant
      prosthodontics.
AB  - The aim of this article was to review the literature on various aspects of
      occlusion related to implant prosthodontics, using PubMed and the Cochrane
      library. Even if the number of studies on implants and prosthodontics is very
      large, no randomized controlled trials or Cochrane reviews were found on the
      possible influence of occlusal design or characteristics of occlusion on
      treatment outcome. Therefore, studies and articles of a lower evidence level were
      accepted as the main part of the review. The widely spread opinion that implants
      are superior to natural teeth was refuted by two recent consensus conferences,
      which concluded that the long-term outcome of implant restorations is not better
      than that of natural teeth. No controlled studies on the optimal features of a
      harmonious natural and/or restored occlusion, including implant prostheses, were
      found. Nor was there any evidence that more sophisticated methods in jaw
      registration, e.g., using face-bows and adjustable articulators, compared with
      simpler methods, will yield better clinical prosthodontic results. This article
      discusses, among other things, concepts of occlusion of implant-supported
      restorations, occlusal material, cantilevers, and occlusal risk factors. Within
      the limitations of the review, it was concluded that many factors can influence
      implant failure and peri-implant bone loss but that little is known of the
      relative importance of such factors. Most probably, however, occlusal factors and
      details of occlusion are in general of minor importance for the outcome of
      implant restorations. Occlusion can be managed successfully by using simple
      methods for jaw registration and different occlusal concepts.

PMID- 19184294
TI  - Immortalization of normal human gingival keratinocytes and cytological and
      cytogenetic characterization of the cells.
AB  - Most in vitro studies of oral carcinogenesis in human cells are carried out with
      oral keratinocytes immortalized by human papillomavirus type 16 DNA. However,
      because various etiological factors for oral cancer are known, it is important to
      establish new human keratinocyte cell lines useful for studying the mechanism of
      oral carcinogenesis. Normal human gingival keratinocytes in secondary cultures
      grown in serum-free medium were either transfected with origin (-) SV40 DNA or
      sequentially transfected with origin (-) SV40 DNA and human c-fos. The
      transfected cells were continually passaged and analyzed for cytological and
      cytogenetic characterizations. Four immortal cell lines were grown for over 1100
      days in culture and maintained a vigorous growth for over 250 population
      doublings. They expressed SV40 T antigen, cytokeratins 8 and 18, and E-cadherin,
      and overexpressed the c-Fos protein. The immortal cell lines had telomerase
      activity but lacked transformed phenotypes on soft agar or in nude mice. Each
      cell line had nonrandom chromosomal abnormalities and minisatellite alterations.
      One of the immortal cell lines, NDUSD-1, retained the capability to deposit
      calcium, which was also demonstrated in normal human gingival keratinocytes by
      alizarin red staining, indicating the possibility that NDUSD-1 cells may retain
      some natural characteristics of normal gingival keratinocytes. Because the oral
      ectoderm plays an important role in tooth development, these immortal cell lines
      may be useful in various experimental models for investigations of oral biology
      and oral carcinogenesis.

PMID- 19184296
TI  - Oral motor function and masticatory performance in the community-dwelling
      elderly.
AB  - This study was performed to ascertain the relationships between oral motor
      functions, such as those of the tongue and lips, and age in the community
      dwelling elderly, as well as to investigate the effects of these factors on
      masticatory performance. The subjects were 268 healthy elderly Japanese living in
      Kyoto. They were divided into four age groups and further classified into the
      following two groups by the presence or absence of posterior occlusal support:
      Eichner A or B1-B3 (group A), and Eichner B4 or C (group B). They were wearing
      removable or fixed dentures if they had missing teeth. Oral function evaluation
      items included (1) masticatory performance and (2) oral motor skills. Significant
      differences were noted among the age groups in tongue pressure within group A (P
      < 0.01) and group B (P < 0.05), and in the number of repetitions of the syllables
      /ta/ and /ka/ in group B (/ta/: P < 0.05, /ka/; P < 0.01). The number of natural
      teeth (beta = 0.463, P < 0.001) in group A and tongue pressure (beta = 0.436, P <
      0.001) in group B were the only predictors of masticatory performance when the
      data were analyzed by multiple regression analysis. The tongue may compensate for
      the missing teeth in masticatory performance of those elderly who have lost their
      natural teeth. The results of this study highlight the importance of tongue
      function in masticatory performance.

PMID- 19184295
TI  - Tannerella forsythia and the HLA-DQB1 allele are associated with susceptibility
      to periodontal disease in Japanese adolescents.
AB  - Periodontal disease is a multiple factor disease caused by genetic factors,
      environmental factors, and periodontal bacteria (periodontal pathogens). The
      present study aimed to elucidate the risk factors for periodontal disease in
      Japanese adolescents. Subjects (11-16 years old) were classified into three
      groups: localized aggressive periodontitis (LAP), periodontal attachment loss
      (PAL), and periodontally healthy (PH) groups. Genomic DNA isolated from the
      buccal mucosa was used for single-nucleotide polymorphism analyses of the
      candidate genes (interleukin-1alpha-889; interleukin-1alpha +4845; interleukin
      1beta +3954; an immunoglobulin G Fc gamma receptor, FcgammaRIIa-R/H131; and a
      human leukocyte antigen class II allele, HLA-DQB1) of aggressive periodontitis.
      Subgingival plaque samples obtained from the same subjects were used for 16S
      rRNAbased polymerase chain reaction analysis of five important periodontal
      pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis,
      Prevotella intermedia, Treponema denticola, and Tannerella forsythia). Tannerella
      forsythia was detected in the deepest periodontal pockets in all subjects in the
      LAP and PAL groups. The prevalence of an atypical BamHI restriction site in HLA
      DQB1 of the LAP group was significantly higher than that in the PH and PAL
      groups. Furthermore, all subjects who had the atypical BamHI restriction site in
      HLA-DQB1 had T. forsythia infection. These results suggested that T. forsythia is
      associated with periodontal disease in Japanese adolescents and also suggested
      that HLA-DQB1 is related to LAP and is associated with T. forsythia infection.

PMID- 19184297
TI  - Effects of maxillary second molar extraction on dentofacial morphology before and
      after anterior open-bite treatment: a cephalometric study.
AB  - The purpose of the present study was to probe into the effects of maxillary
      second molar extraction on dentofacial morphology by the use of cephalometric
      radiographs taken before and after anterior open-bite treatment. The subjects
      were 30 Japanese patients who had received multiloop edgewise archwire therapy
      without premolar extraction. They were divided into two groups. Group 1 consisted
      of 15 patients who had their maxillary second molars removed. Group 2 comprised
      15 patients who had been treated without extraction of maxillary second molars.
      Lateral cephalograms were taken before and after treatment. Seventeen angular and
      31 linear measurements were obtained from the lateral cephalograms. Paired and
      unpaired t tests were used to determine the significance of differences in
      measurements. The retrusion and extrusion of the maxillary incisors, the distal
      movement of the maxillary first molars, and the uprighting of the maxillary first
      premolars and the mandibular first molars were greater in group 1 than in group
      2. Moreover, the maxillary first molars intruded significantly in group 1 but
      extruded insignificantly in group 2. Extraction of maxillary second molars, as
      well as nonextraction, can be an effective operating procedure for open-bite
      correction of the permanent dentition.

PMID- 19184298
TI  - Mandibular permanent second molar with four roots and root canals: a case report.
AB  - Although four-rooted mandibular first molars have been observed on a few
      occasions in the literature, to the best of our knowledge, four-rooted second
      molars have not been reported. Here, we describe a mandibular second molar with
      four roots and canals: two mesial and two distal. Mesial roots were separated in
      the cervical one-third near the cervical margin, while distal roots were divided
      at a lower level in the middle one-third of the root. We discuss the possibility
      of different root and canal variations of the mandibular second molar from a
      developmental point of view.

PMID- 19184299
TI  - Trigeminal neuralgia secondary to epidermoid cyst at the cerebellopontine angle:
      case report and brief overview.
AB  - Trigeminal neuralgia (TN) is a paroxysmal shock-like pain restricted to the
      innervations of the areas of one or more trigeminal branches, often set off by
      light stimuli in a trigger zone. Pain attacks occur spontaneously, and can also
      be triggered by a nonpainful sensory stimulus to the skin, intraoral mucosa
      surrounding the teeth, or tongue. The pathogenesis of TN is uncertain and
      typically is idiopathic, but it may be due to a structural lesion. Various
      proposed causes include traumatic compression of the trigeminal nerve by
      neoplastic or vascular anomalies, infectious agents such as human herpes simplex
      virus, and intracranial tumors or demyelinating conditions such as multiple
      sclerosis. Here we report a case of a young patient diagnosed with trigeminal
      neuralgia secondary to epidermoid cyst at the cerebellopontine angle.

PMID- 19184300
TI  - Immunocytochemical study of granular duct cells with a hormonally enhanced
      granular cell phenotype in the mouse parotid gland.
AB  - In the parotid glands (PGs) of intact male mice (12 weeks of age, ICR strain),
      immunofluorescence labels for a true tissue kallikrein, mK1, and for nerve growth
      factor (NGF) were recognized through the subluminal edges of the striated duct
      (SD) segments and interlobular duct segments. Because of their small size,
      secretory granules were not detectable by light microscopy in any of the duct
      cells. Full-fledged granular cells, containing large secretory granules that were
      visible by light microscopy, were induced in the SD segments of male mice after
      the injection of 5alpha-dehydrotestosterone (DHT) and triiodothyronine (T(3)),
      given either alone or in combination every other day for 2 weeks. A stronger
      effect was detected in the mice that were concomitantly injected with DHT and
      T(3), and more abundant, fully developed granular cells appeared in the SD
      segments of these mice. These full-fledged granular cells were immunoreactive for
      mK1, NGF, and epidermal growth factor, but not for renin. The present results
      indicate that some of the SD cells with small granules in the mouse PG can
      develop a granular cell phenotype, producing more kinds of growth factors, as a
      result of the actions of androgen and thyroid hormone.

PMID- 19184301
TI  - Effects of corneal thickness on intraocular pressure measured with three
      different tonometers.
AB  - PURPOSE: To compare intraocular pressure (IOP) measured by a Goldmann applanation
      tonometer (GAT), a noncontact tonometer (NCT), and a portable noncontact
      tonometer (PNCT) in eyes of healthy volunteers, and to determine if a significant
      correlation exists between the IOP and the central corneal thickness (CCT).
      METHODS: A total of 144 healthy participants were randomly assigned to one of two
      groups; in the first group, IOP was measured first with the NCT and then with the
      GAT. In the second group, IOP was measured first with the PNCT and then with the
      GAT. Subsequently, the CCT of all subjects was measured with an ultrasonic
      pachymeter. RESULTS: The IOPs determined by the GAT and NCT and were strongly
      correlated, as were those determined by the GAT and PNCT, in both groups.
      However, a Bland-Altman plot showed that the correlations between the GAT and NCT
      and between the GAT and the PNCT measurements were not significant. With all
      three instruments, the IOP readings varied with the CCT. The mean IOPs obtained
      with the GAT increased by 0.23 mmHg with each 10-microm increase in CCT (0.23
      mmHg/10 microm). The comparable value for the NCT was 0.29 mmHg/10 microm, and
      that for the PNCT was 0.31 mmHg/10 microm. CONCLUSIONS: For measurements of IOP
      in normal eyes, the GAT is the tonometer least affected by the CCT, compared with
      the PNCT and NCT. A PNCT is more likely to be affected by variations in CCT than
      the GAT.

PMID- 19184302
TI  - Central corneal thickness in Japanese children.
AB  - PURPOSE: To determine the central corneal thickness (CCT) in Japanese children
      and to investigate the changes in CCT with increasing age. METHODS: Pachymetry
      was performed on 338 eyes of 169 patients undergoing eye muscle surgery under
      general anesthesia, and the intraocular pressure (IOP) was measured on 312 eyes
      of 156 of those same patients. Patients with abnormalities other than refractive
      errors and strabismus were excluded. Patients were divided into four groups:
      group 1, < or =1 year of age; group 2, 2-4; group 3, 5-9; and group 4, 10-18
      years of age. Analysis of variance (ANOVA) was performed to determine the
      significance of the changes in CCT. RESULTS: The average CCT of the right eye was
      544.3 +/- 36.9 microm. The CCT was thinner in group 1 than in groups 3 and 4
      (ANOVA, P = 0.02). There was a positive but weak correlation between IOP and CCT
      (IOP = 6.253 + 0.014 x CCT; r (2) = 0.047, P = 0.007). CONCLUSIONS: CCT reaches
      the adult thickness in Japanese children by age 5 years. The average CCT is
      thinner in Japanese children than in Caucasians but thicker than in African
      American children.

PMID- 19184303
TI  - Age-related changes of phoria myopia in patients with intermittent exotropia.
AB  - PURPOSE: To investigate the age-related changes in a myopic shift under binocular
      conditions (phoria myopia) in patients with intermittent exotropia (IXT).
      METHODS: Forty-five patients with IXT were studied: 21 were < or =9 years old
      (children), 11 were between 10 and 19 years (adolescents), and 13 were between 20
      and 43 years (adults). The angle of strabismus was determined by the alternating
      prism cover test. The spherical refractive error was measured at 1 m using
      infrared video retinoscopy under monocular and binocular viewing conditions.
      RESULTS: The change in the spherical refractive error (DeltaR) between binocular
      and monocular conditions was significantly larger in adults (DeltaR = -1.11 +/-
      1.01 diopters (D), average +/- standard deviation) than in children (DeltaR = 
      0.34 +/- 0.34 D; P < 0.05, analysis of variance). DeltaR was significantly
      correlated with the angle of exotropia only in adults (r = 0.55, P = 0.04). After
      strabismus surgery, DeltaR decreased in adults (n = 3). CONCLUSIONS: Because a
      significant myopic shift under binocular conditions was detected in IXT patients
      older than 20 years, phoria myopia can occur after age 20 even if functional
      disturbances are not observed in children or adolescent IXT patients, a fact that
      specialists need to bear in mind when treating younger patients.

PMID- 19184304
TI  - Effect of travoprost on intraocular pressure during 12 months of treatment for
      normal-tension glaucoma.
AB  - PURPOSE: To evaluate the intraocular pressure (IOP)-lowering effect of travoprost
      in normal-tension glaucoma (NTG) over a 12-month follow-up. METHODS: Forty-five
      eyes of 45 patients with unilateral NTG were treated with travoprost (0.004%)
      once a day for 12 months. Mean IOP and the IOP reduction from baseline were
      assessed at 0.5, 1, 3, 6, 9, and 12 months after the initiation of the treatment.
      Adverse ocular event frequency and the frequency of discontinuation of treatment
      due to adverse events were evaluated. RESULTS: Mean IOP during 12 months of
      travoprost treatment ranged from 11.17 to 11.82 mmHg, and the mean IOP reduction
      in relation to baseline IOP from -2.71 to -3.71 mmHg (-18.3% to -25.1%). Mean IOP
      and IOP changes in the travoprost-treated and control groups were significantly
      different at every follow-up (P < 0.05 in each case). Both the magnitude (r =
      0.6992) and percentage (r = 0.5464) of IOP reductions correlated positively with
      baseline IOP values. Ocular adverse events were usually mild to moderate and
      resolved without treatment. CONCLUSIONS: Travoprost was well tolerated and
      significantly reduced IOP in NTG patients. In addition, initial IOP reductions
      were maintained throughout follow-up. Travoprost was found to be more effective
      in patients with greater baseline IOP.

PMID- 19184305
TI  - Interpretation of the Humphrey Matrix 24-2 test in the diagnosis of preperimetric
      glaucoma.
AB  - PURPOSE: To define the diagnostic precision of the Humphrey Matrix 24-2 test and
      to determine a clinically applicable cutoff criterion for the inclusion of
      preperimetric glaucoma. METHODS: Eyes with preperimetric glaucoma (99 eyes) were
      defined as having normal standard automated perimetry (SAP) results and a
      glaucomatous optic nerve head, along with one or more optical coherence
      tomography (OCT) parameters flagged as <0.05 or a retinal nerve fiber layer
      (RNFL) defect on red-free fundus photographs. Normal controls (122 eyes) were
      defined as having a normal optic disc and RNFL with normal SAP. Receiver
      operating characteristic (ROC) curves were constructed to determine the best
      discriminating parameter of the frequency-doubling technology (FDT) Matrix. The
      sensitivity, specificity, and hit ratio of all available criteria were calculated
      from the FDT Matrix. RESULTS: Pattern standard deviation (PSD) showed a larger
      area under the ROC curve (AUC) (0.767) than mean deviation (MD) (0.619). A
      pattern deviation plot (PDP) analysis by modified Anderson criteria showed the
      highest discriminating power, with a sensitivity of 75.76%, followed by a PSD
      cutoff value of 3.14 dB (sensitivity, 73.74%). CONCLUSIONS: FDT Matrix seems to
      be a valuable clinical tool in the detection of preperimetric glaucoma. Among the
      parameters of the FDT Matrix, PDP analysis by modified Anderson criteria may
      provide a reliable cutoff criterion.

PMID- 19184306
TI  - Electroretinograms in three cases of Creutzfeldt-Jakob disease with visual
      disturbances.
AB  - PURPOSE: To report three cases of idiopathic Creutzfeldt-Jakob disease (CJD) with
      visual symptoms. CASES: Patient 1 initially visited our ophthalmology department
      complaining of blurred vision. Electro-retinography (ERG) showed a selective
      reduction of the b wave before she was diagnosed with CJD. Patient 2 had normal
      ERG results even with severely advanced CJD. However, a reduction of the b wave
      on ERG was observed 1 month before the patient died. Patient 3 had visual
      disturbances at the initial visit, but the ERG result was normal even after the
      CJD had advanced. Atrophy of the visual cortex was later observed. OBSERVATIONS:
      CJD can alter the vision in various ways. The selective reduction of the b wave
      on ERG indicates the retinal involvement. However, visual disturbances may occur
      without the retinal implications. CONCLUSION: Ophthalmologists should be aware
      that the visual impairment can be the first symptom of CJD.

PMID- 19184308
TI  - Etiology of carotid cavernous fistula in Japanese.
AB  - BACKGROUND: A carotid cavernous fistula (CCF) develops spontaneously or after
      trauma, and older publications suggest that the majority of CCF cases are caused
      by trauma. However, more recent reports question the prevalence of CCFs caused by
      trauma. METHODS: The clinical records of 37 consecutive patients diagnosed with a
      CCF were reviewed. The disease etiology, patient demographics, anatomical
      classification, and clinical course were investigated. RESULTS: The CCF was
      spontaneous in 30 patients, and was related to head or neck trauma in seven
      patients. The mean age of all patients was 65.8 +/- 10.5 years, and 30 (81.1%)
      were women. Eight had diabetes and 14 had hypertension. The major signs and
      symptoms were congestion (86.4%), diplopia (81.1%), bruit (59.5%), and
      headaches/orbital pain (62.2%). Exophthalmos (67.6%) and elevated intraocular
      pressure (40.5%) were also frequently noted. In the Barrow classification, seven
      patients were classified as type A, four as type B, three as type C, and 20 as
      type D. The classification could not be established in three patients who did not
      undergo angiography. Of note, almost all patients had consulted an
      ophthalmologist before the diagnosis. CONCLUSION: Spontaneous/low-flow CCF is
      more prevalent than previously reported. The role of ophthalmologists is
      important because the majority of patients initially consult ophthalmologists,
      and the signs of low-flow CCF are subtle and may be overlooked.

PMID- 19184307
TI  - Prognostic factors and treatment outcomes of retinoblastoma in pediatric
      patients: a single-institution study.
AB  - PURPOSE: Since 1997, our institute has used neoadjuvant chemotherapy for
      intraocular retinoblastoma. However, some of the patients showed signs of
      recurrence months to years later. We therefore attempted to determine the
      prognostic factors of treatment outcomes and survival in our patients. METHODS:
      We reviewed 90 patients treated from 1997 to 2006. The following information was
      recorded: demographic and ophthalmological data, clinical classification,
      histopathological data, and treatment methods and outcomes. RESULTS: Enucleation
      was avoided in two of 57 eyes in the unilateral group. Sixteen of 54 eyes in the
      bilateral group were salvaged by systemic chemotherapy with local treatment.
      There was no difference in histopathological findings between the two groups.
      Nine of 57 patients in the unilateral group demonstrated poor outcomes, compared
      with four of 27 in the bilateral group. Significant poor prognostic factors for
      survival were optic nerve head invasion, orbital involvement, abnormal results on
      bone marrow aspiration, lumbar puncture, bone scan, and group E or F
      classification. CONCLUSIONS: The 15% mortality rate in our patients is slightly
      higher than that reported in developed countries. Delayed diagnosis and treatment
      is the main cause of avoidable deaths. Improving education of both clinicians and
      parents would increase survival rates in this potentially fatal disease.

PMID- 19184309
TI  - Reactivation of thyroid-associated orbitopathy after cataract surgery.
AB  - BACKGROUND: We describe an episode of thyroid-associated orbitopathy (TAO)
      following sequential bilateral cataract surgery. CASE: We report the case of an
      80-year-old woman who developed TAO in 2000. OBSERVATIONS: After an episode of
      mild TAO, the patient's condition was stable and quiescent for 4 years. Following
      cataract surgery on her right eye in 2004, there was rapid worsening of the TAO
      bilaterally that lasted approximately 12 months. Her condition then stabilized
      for 2 years. In 2007, she had cataract surgery on the left eye and the TAO again
      worsened bilaterally. CONCLUSION: Cataract surgery may lead to recrudescence of
      TAO in predisposed individuals.

PMID- 19184310
TI  - Photoprotective effect of yellow-tinted intraocular lenses.
AB  - PURPOSE: The aim of this study was to experimentally investigate changes in
      visible light-induced photo-oxidation and to evaluate the inhibitory effect of
      various acrylic tinted intraocular lenses (IOLs) on photooxidation. METHODS:
      Three types of nontinted (VA-60BB, HOYA; SA60AT, Alcon; AU-6, Menicon) and tinted
      (YA-60BB, HOYA; SN60AT, Alcon; AN-6, Menicon) IOLs were used. In the first
      experiment, we investigated oxidation related to ultraviolet rays by using a
      mixed solution of reduced glutathione, nicotinamide adenine dinucleotide
      phosphate (NADPH), and glutathione reductase. The mixed glutathione solution was
      irradiated for 30, 60, or 90 min with direct artificial sunlight or artificial
      sunlight that had been passed through various IOLs. Oxidation was detected at 340
      nm. In the second experiment, human retinal pigment epithelium (RPE) cells were
      prepared and cultured in a 96-well dish until confluent. After light exposure for
      30 min or 48 h, lactate dehydrogenase (LDH) levels of the culture supernatant
      were measured to assess the amount of cell damage. RESULTS: Visible light-induced
      glutathione oxidation progressed over time. Intraocular lenses inhibited
      photooxidation, with the inhibitory effect shown to increase when tinted IOLs
      were used. LDH levels in RPE cells increased as a result of exposure to visible
      light. There was a higher increase in LDH with nontinted than with tinted IOLs.
      CONCLUSION: Visible light causes photooxidation, which damages intraocular tissue
      in vitro. These results suggest that tinted IOLs effectively inhibit tissue
      damage from visible light.

PMID- 19184311
TI  - Severe choroidal ischemia following photodynamic therapy for pigment epithelial
      detachment and chronic central serous chorioretinopathy.
AB  - BACKGROUND: Photodynamic therapy (PDT) has proven beneficial in the treatment of
      central serous chorioretinopathy (CSC). CASES: Two patients with serous pigment
      epithelial detachments (PEDs) and one patient with chronic CSC developed an
      abrupt visual loss caused by severe choroidal ischemia following PDT. Serous PEDs
      in the two patients were regarded as a latent variant of CSC. PDT was performed
      in accordance with the Treatment of Age-Related Macular Degeneration with
      Photodynamic Therapy guidelines. OBSERVATIONS: Although following PDT, PEDs and
      serous sensory retinal detachments resolved in all patients, the laser-treated
      areas of the patients revealed severe choroidal ischemia and their visual acuity
      decreased. Only in case 1 did visual acuity recover to the pretreatment level 2
      months after treatment. In case 2, visual acuity was still reduced 7 months after
      treatment. In case 3, secondary choroidal neovascularization developed in the
      treatment area 1 month after treatment. CONCLUSIONS: In the CSC variant
      associated with PED only or in chronic CSC, PDT performed by the standard
      procedure can increase the risk of severe choroidal ischemia. Further studies are
      needed to find safe and optimal PDT parameters.

PMID- 19184312
TI  - Intravitreal bevacizumab for choroidal neovascularization secondary to Vogt
      Koyanagi-Harada syndrome.
AB  - BACKGROUND: Vogt-Koyanagi-Harada (VKH) syndrome is characterized by bilateral
      diffuse uveitis associated with auditory, neurological, and cutaneous signs and
      symptoms. VKH syndrome is a cell-mediated autoimmune disease against melanocytes.
      Choroidal neovascularization (CNV) occurs in 15% of VKH patients and is
      associated with poor visual prognosis. CASES: We report on two patients with VKH
      syndrome and CNV that were treated with intravitreal bevacizumab. OBSERVATIONS:
      One of the VKH patients also had an extrafoveal CNV membrane and underwent
      multiple intravitreal injections of bevacizumab in combination with laser
      photocoagulation, with subsequent improvement in visual acuity. The second had a
      subfoveal CNV that responded to a single intravitreal injection of bevacizumab.
      CONCLUSION: Intravitreal bevacizumab may be a useful drug to treat CNV in eyes
      with VKH syndrome.

PMID- 19184313
TI  - Severe methicillin-resistant Staphylococcus aureus infection after multilayer
      amniotic membrane transplantation.

PMID- 19184314
TI  - Residual amounts of ophthalmic viscosurgical devices on the corneal endothelium
      following phacoemulsification.

PMID- 19184315
TI  - Eye-shadow particles under a laser in situ keratomileusis flap following corneal
      trauma.

PMID- 19184316
TI  - Langerhans cell histiocytosis limited to the eyelid margin.

PMID- 19184317
TI  - Ocular hypertelorism and exotropia as presenting signs in Diamond-Blackfan
      anemia.

PMID- 19184318
TI  - End-stage glaucoma in Stevens-Johnson syndrome.

PMID- 19184319
TI  - Adult T-cell leukemia presenting with episcleritis and secondary glaucoma.

PMID- 19184320
TI  - Reticular crack lesion in the ocular fundus.

PMID- 19184321
TI  - Decompression retinopathy and serous retinal detachment after trabeculotomy in a
      patient with systemic amyloidosis.

PMID- 19184322
TI  - Early onset of rhegmatogenous retinal detachment after LASIK with femtosecond
      laser.

PMID- 19184323
TI  - Familial cerebral cavernous malformation: report of a further Italian family.
AB  - Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause
      seizures, headaches, intracerebral hemorrhages, and focal neurological deficits;
      they can also be clinically silent and may occur as a sporadic or an autosomal
      dominant condition. Three genes have been identified as causing familial CCM:
      KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3, mapping, respectively, on chromosomes
      7q, 7p, and 3q. This is a report on an Italian family affected by CCM due to a
      KRIT1 gene mutation on exon 13. The mother suffered from a cerebellar hematoma
      and was severely disabled; one son had suffered from intractable seizures and
      underwent surgery for removal of a cavernous angioma, while another son was
      asymptomatic. Brain MRI showed CCMs in all patients. This report underlines that
      a familial form of CCM could be suspected when a patient presents with multiple
      CCMs; neurologists and neurosurgeons should be aware that genetic testing for
      these forms is available.

PMID- 19184324
TI  - The neuropsychological and neuroradiological correlates of slowly progressive
      visual agnosia.
AB  - The case of a 64-year-old woman affected by slowly progressive visual agnosia is
      reported aiming to describe specific cognitive-brain relationships. Longitudinal
      clinical and neuropsychological assessment, combined with magnetic resonance
      imaging (MRI), spectroscopy, and positron emission tomography (PET) were used.
      Sequential neuropsychological evaluations performed during a period of 9 years
      since disease onset showed the appearance of apperceptive and associative visual
      agnosia, alexia without agraphia, agraphia, finger agnosia, and prosopoagnosia,
      but excluded dementia. MRI showed moderate diffuse cortical atrophy, with
      predominant atrophy in the left posterior cortical areas (temporal, parietal, and
      lateral occipital cortical gyri). 18FDG-PET showed marked bilateral posterior
      cortical hypometabolism; proton magnetic resonance spectroscopic imaging
      disclosed severe focal N-acetyl-aspartate depletion in the left temporoparietal
      and lateral occipital cortical areas. In conclusion, selective metabolic
      alterations and neuronal loss in the left temporoparietooccipital cortex may
      determine progressive visual agnosia in the absence of dementia.

PMID- 19184325
TI  - Smoking as a precipitating factor for migraine: a survey in medical students.
AB  - Our aim was to analyse the relationship between migraine and smoking in medical
      students. Medical students who had already received teaching on migraine were
      asked to answer an ad hoc questionnaire. A total of 361 students filled in the
      questionnaire: 245 (68%) were women. International Headache Society criteria were
      fulfilled by 58 (prevalence of migraine 16%) students. A total of 74 (20%) were
      current smokers: 21 males (18% of men were smokers) and 53 females (22% smokers).
      Within those 58 students with migraine, 17 (29%) smoke: only 2 were males (14% of
      males with migraine smoked) while the remaining 15 were females (34% of women
      with migraine smoked). Within those 17 students who were smokers and migraineurs,
      12 (71%) thought that smoking worsens migraine and 10 (59%) that smoking
      precipitates attacks. The minimum number of cigarettes which subjectively
      precipitates attacks was 5. Migraine prevalence in the 20s in Spain is 16%. Our
      data obtained in medical students suggest that smoking can be a precipitating
      factor for migraine attacks, as the prevalence of active smoking is one-third
      higher in migraineurs and as there seems to be a relationship between the number
      of cigarettes and the development of migraine attacks.

PMID- 19184326
TI  - Alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase activity in the sera
      of patients with esophageal cancer.
AB  - Various alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH)
      exist in the human esophageal mucosa. In our last experiments we have shown that
      ADH and ALDH are present also in the esophageal cancer cells. Moreover, the
      activities of total ADH and class IV isoenzymes were significantly higher in
      cancer tissue than in healthy mucosa, which suggests that these changes may be
      reflected by enzyme activity in the serum. Therefore, we measured the activity of
      total alcohol dehydrogenase, and classes I-IV of this enzyme and aldehyde
      dehydrogenase in the sera of patients with this cancer. Serum samples were taken
      for routine biochemical investigation from 67 patients with esophageal cancer
      before treatment. Total ADH activity was measured by photometric method with p
      nitrosodimethylaniline (NDMA) as a substrate and ALDH activity by the
      fluorometric method with 6-methoxy-2-naphtaldehyde as a substrate. For the
      measurement of the activity of class I and II isoenzymes, we employed the
      fluorometric methods, with class-specific fluorogenic substrates. The activity of
      class III alcohol dehydrogenase was measured by the photometric method with
      formaldehyde and class IV with m-nitrobenzaldehyde as a substrate. A
      statistically significant increase of class IV alcohol dehydrogenase isoenzymes
      was found in the sera of cancer patients. The median activity of this class
      isoenzyme in the total cancer group increased by about 26.5% (7.42 mU/l) in
      comparison to the control level (5.46 mU/l). The total alcohol dehydrogenase
      activity was significantly higher (30%) among patients with cancer. The
      activities of other tested ADH isoenzymes and total ALDH were unchanged. The
      activity of the class I ADH isoenzyme was significantly higher in the sera of
      drinkers with esophageal cancer than non-drinking patients. The increased total
      activity of alcohol dehydrogenase and class IV isoenzyme in the sera of patients
      with esophageal cancer probably can be caused by release of this isoenzyme from
      cancer cells or might be stimulated by alcohol drinking.

PMID- 19184328
TI  - The cross-reactivity of anti-asparaginase antibodies against different L
      asparaginase preparations.
AB  - Repeated administration of L-asparaginase leads to the development of specific
      antibodies and hypersensitivity reactions. The aim of the study was to evaluate a
      possible cross-reaction of anti-asparaginase antibodies, developed against the
      native E. coli L-asparaginase (Asparaginase Medac), with other preparations of
      the enzyme. Sixteen patients with acute lymphoblastic leukemia, in whom in the
      reinduction phase of treatment hypersensitivity against L-asparaginase was
      observed and/or the presence of anti-asparaginase antibodies was established were
      recruited for the present study. Ten out of 16 tested sera showed cross
      immunoreactivity to PEG-asparaginase, while no reactivity to L-asparaginase
      derived from Erwinia chrysantemi was observed. Since cross-reacting antibodies
      were also found in sera of patients with no overt allergic reaction, L: 
      asparaginase may undergo silent inactivation during the reinduction phase of
      therapy. This finding is of clinical importance with regard to appropriate dosage
      and necessitates careful enzyme activity monitoring in all patients undergoing
      repeated treatment with various L-asparaginase preparations.

PMID- 19184327
TI  - Bacteriophage interactions with phagocytes and their potential significance in
      experimental therapy.
AB  - Bacteriophages are among the most numerous creatures on earth and they are
      omnipresent. They are thus in constant natural contact with humans and animals.
      However, the clinical and technological use of bacteriophages has also become
      more frequent, which is why all aspects of phage-mammal interactions need to be
      explored. Bacteriophages are able to interact with mammalian phagocytes. They may
      inhibit the phagocytosis of bacteria, but they may also undergo phagocytosis
      themselves. The ability of bacteriophages to reduce reactive oxygen species
      production by polymorphonuclear leukocytes in the presence of bacteria or their
      endotoxins was also confirmed. Studies show that the high immunogenicity of
      bacteriophages may also be employed in anti-tumor treatment. The present
      knowledge of phage interactions with cellular components of the mammalian immune
      system is sparse and insufficient, especially considering the increasing interest
      in the application of these viruses in human life. We believe that continuation
      of such research is indispensable.

PMID- 19184330
TI  - Postpartum bilateral transient osteoporosis of the hip.

PMID- 19184329
TI  - Promoter methylation of protease-activated receptor (PAR2) is associated with
      severe clinical phenotypes of ulcerative colitis (UC).
AB  - Tryptase acting at protease-activated receptor 2 (PAR2) contributes to the
      pathogenesis of Inflammatory bowel diseases (IBDs). DNA methylation has been
      shown to be an important mechanism in gene silencing. We attempted to clarify the
      relationship between the promoter methylation of PAR2 and ulcerative colitis
      (UC). 84 UC patients enrolled in the study. UC patients were classified by
      disease behavior, severity and extent of disease. For rectal inflammatory mucosal
      specimens from all the patients, and normal terminal ileum from 23 patients,
      promoter methylation of PAR2 gene was quantified by digital densitographic
      analysis following to methylation-specific polymerase chain reaction (MSP). The
      mean methylation levels of the PAR2 gene in all 84 subjects was 38.4 +/- 19.6%.
      Although mean methylation levels in rectal inflammatory mucosa, and paired normal
      terminal ileum did not vary, methylation levels of PAR2 gene was significantly
      higher in total colitis than rectal colitis (total colitis vs. rectal colitis;
      42.9 +/- 19.6% vs. 34.5 +/- 18.9%, P = 0.046). The higher methylation levels were
      also associated with Steroid-dependent (P = 0.002) and refractory (P = 0.007) UC.
      Our data suggest that PAR2 methylation status in rectal mucosa correlates with
      more severe disease phenotypes of UC.

PMID- 19184331
TI  - Hygiene precautions and the transmission of infections in radiology.
AB  - Healthcare-associated infections are a critical challenge for the public health
      sector. Most are acquired through contact, predominantly with the hands of health
      care personnel. Hand hygiene, therefore, is the single most effective measure for
      preventing and controlling infectious diseases. Recently, cases of acute
      hepatitis C occurred in patients who had undergone contrast-enhanced computed
      tomography. This was probably related to inadequate handling by health care
      staff. Rigorous compliance with standard precautions is therefore compulsory even
      in radiology, a setting traditionally considered at low risk for the transmission
      of pathogens. Adherence to standard precautions is still poor and the persistence
      of inappropriate practices responsible for preventable incidents is very common
      in radiology, often owing to underestimation of risk. Radiology units must
      promote compliance with correct hand hygiene through appropriate education
      programmes and provision of adequate areas and hand hygiene products. The
      evidence base to support the use of alcohol-based hand rub is demonstrating that
      these formulations are effective in improving hand hygiene compliance and
      preventing infections.

PMID- 19184332
TI  - Role of high-resolution ultrasonography without and with real-time spatial
      compound imaging in evaluating the injured posterior cruciate ligament:
      preliminary study.
AB  - PURPOSE: This study sought to compare high-resolution ultrasonography (HRUS)
      without and with compound imaging in evaluating the injured posterior cruciate
      ligament (PCL). MATERIALS AND METHODS: Thirteen patients with a magnetic
      resonance imaging (MRI) diagnosis of PCL lesions (ten acute and three chronic)
      and 20 healthy controls underwent conventional and compound HRUS performed by the
      same radiologist who was blinded to the subjects' case-control status. The PCL
      was scanned in a longitudinal direction in all cases. HRUS images were assessed
      for PCL thickness by two other radiologists blinded to the number and type of PCL
      injury. PCLs were classified as normal or injured, and the latter as having acute
      or chronic injuries. Inter-method reproducibility of measuring PCL thickness was
      assessed on conventional and compound HRUS images. RESULTS: Complete agreement in
      classifying normal or injured PCL and acute or chronic PCL injuries was achieved.
      PCL thickness in volunteers was 4.5+/-0.7 mm on conventional images and 4.6+/-0.7
      mm on compound images. On conventional and compound HRUS images, the thickness of
      acutely injured PCL was 9.1+/-1.5 mm and 9.2+/-1.7 mm, respectively, and that of
      chronically injured PCL was 7+/-0.9 mm and 7+/-0.8 mm. Inter-method
      reproducibility of PCL thickness measurements on conventional vs. compound HRUS
      images was 98.6%. CONCLUSIONS: HRUS is a reliable technique for studying the PCL
      and detecting PCL injuries.

PMID- 19184333
TI  - Elevated endogenous GABA concentration attenuates glutamate-glutamine cycling
      between neurons and astroglia.
AB  - In this study, the relationship between endogenous brain GABA concentration and
      glutamate-glutamine cycling flux (V (cyc)) was investigated using in vivo (1)H
      and (1)H{(13)C} magnetic resonance spectroscopy techniques. Graded elevations of
      brain GABA levels were induced in rat brain after administration of the highly
      specific GABA-transaminase inhibitor vigabatrin (gamma-vinyl-GABA). The glial
      specific substrate [2-(13)C]acetate and (1)H{(13)C} magnetic resonance
      spectroscopy were used to measure V (cyc) at different GABA levels. Significantly
      reduced V (cyc) was found in rats pretreated with vigabatrin. The reduction in
      group mean V (cyc) over the range of GABA concentrations investigated in this
      study (1.0 +/- 0.3-5.1 +/- 0.5 micromol/g) was found to be nonlinear: Delta V
      (cyc)/V (cyc) = [GABA (micromol/g)](-0.35 )- 1.0 (r (2) = 0.98). The results
      demonstrate that V (cyc) is modulated by endogenous GABA levels, and that
      glutamatergic and GABAergic interactions can be studied in vivo using noninvasive
      magnetic resonance spectroscopy techniques.

PMID- 19184334
TI  - Transcription factor AP-2 beta genotype and psychosocial adversity in relation to
      adolescent depressive symptomatology.
AB  - The aim of this study was to investigate possible interactions between the gene
      coding for activating protein-2 beta (AP-2 beta) and psychosocial factors to
      predict depressive symptoms in adolescents. Two-hundred 16- and 19-year-old
      adolescents from the county of Vastmanland, Sweden, were asked to complete a
      questionnaire, interviewed about psychosocial risk factors, and genotyped with
      regard to the transcription factor AP-2 beta intron 2 polymorphism. AP-2 beta
      genotype interacted significantly both with type of housing and parental
      separation to predict depressive symptoms. Individuals who were homozygous for
      the short AP-2 beta allele displayed higher depression scores when psychosocial
      adversity was taken into account. Amongst carriers of one or two copies of the
      long allele, there was no difference in depressive symptoms despite differences
      in psychosocial environments.

PMID- 19184335
TI  - Neuregulin 1 and age of onset in the major psychoses.
AB  - Genetic vulnerability to psychiatric illness extends across major psychiatric
      illness. Neuregulin 1 (NRG1) is a large gene on chromosome 8p, that has been
      identified as a susceptibility factor in bipolar disorder and schizophrenia. In
      particular, a core at risk haplotype has received considerable attention for a
      putative role in the pathophysiology of the major psychoses (schizophrenia and
      bipolar disorder). This core haplotype can be represented by three markers 478B14
      848, 420M9-1395, and SNP8NRG221533. We genotyped 312 families with bipolar
      probands, and 120 families with schizophrenia probands. Association of the core
      haplotype was tested for with age-at-onset and with three phenotypes: major
      psychosis, schizophrenia, and bipolar disorder. Neither age of onset (P = 0.893)
      nor the major psychosis phenotype (P = 0.374) was associated with the core
      haplotype in the overall sample. Ours was the first study to investigate the NRG1
      core haplotype with age of onset of major psychoses, and despite our preliminary
      negative findings, this area deserves further investigation.

PMID- 19184336
TI  - PHF-like tau phosphorylation in mammalian hibernation is not associated with p25
      formation.
AB  - In Alzheimer's disease and related disorders, hyperphosphorylation of tau is
      associated with an increased activity of cyclin dependent kinase 5 (cdk5).
      Elevated cdk5 activity is thought to be due to the formation of p25 and thereby
      represents a critical element in the dysregulation of tau phosphorylation under
      pathological conditions. However, there is still a controversy regarding the
      correlation of p25 generation and tau pathology. Recently, we demonstrated
      physiological, paired helical filament-like tau phosphorylation that reversibly
      occurs in hibernating mammals. Here we used this model to test whether the tau
      phosphorylation in hibernation is associated with the formation of p25. Analysing
      brain material of arctic ground squirrels and Syrian hamsters we found no
      evidence for a hibernation dependent generation of p25. Hence, we suppose that
      phosphorylation of tau does not require the formation of p25. Instead we suggest
      that the truncation of p35 to p25 represents a characteristic of pathological
      alterations and may contribute to aggregation and deposition of
      hyperphosphorylated tau.

PMID- 19184337
TI  - Association of CETP polymorphisms with the risk of vascular dementia and white
      matter lesions.
AB  - Cholesteryl ester transfer protein (CETP), a component of the high density
      lipoprotein (HDL), plays a central role in reverse cholesterol transport. We
      investigated the association of two putative functional CETP polymorphisms (C
      629A and I405V) with the risk of vascular dementia (VD) and tested if this
      association is influenced by the presence of APOE4 allele. Our study included 163
      VD patients (mean age: 74.25 +/- 7.9 years) and 452 cognitively healthy probands
      (mean age: 70.81 +/- 7.9 years). As a biological correlate, the association of
      CETP gene variants with white matter lesion (WML) load was investigated. Neither
      the C-629A (P = 0.169) nor the I405V (P = 0.840) polymorphism was associated with
      VD risk in the whole sample. However, in non-carriers of the APOE4 allele,
      homozygote carriers of the CETP C-629A A allele presented with an increased risk
      of VD (P = 0.01). Whereas in APOE4 carriers, no association of CETP polymorphisms
      with VD risk was detected. In addition, carriers of the CETP C-629A AA genotype
      presented with decreased WML load in the frontal brain (P = 0.009). Our results
      suggest that CETP gene polymorphisms might influence WML load and the risk of VD,
      the latter in non-carriers of the APOE4 allele.

PMID- 19184338
TI  - Expressing a whitefly GroEL protein in Nicotiana benthamiana plants confers
      tolerance to tomato yellow leaf curl virus and cucumber mosaic virus, but not to
      grapevine virus A or tobacco mosaic virus.
AB  - Transgenesis offers many ways to obtain virus-resistant plants. However, in most
      cases resistance is against a single virus or viral strain. We have taken a novel
      approach based on the ability of a whitefly endosymbiotic GroEL to bind viruses
      belonging to several genera, in vivo and in vitro. We have expressed the GroEL
      gene in Nicotiana benthamiana plants, postulating that upon virus inoculation,
      GroEL will bind to virions, thereby interfering with pathogenesis. The transgenic
      plants were inoculated with the begomovirus tomato yellow leaf curl virus (TYLCV)
      and the cucumovirus cucumber mosaic virus (CMV), both of which interacted with
      GroEL in vitro, and with the trichovirus grapevine virus A (GVA) and the
      tobamovirus tobacco mosaic virus (TMV), which did not. While the transgenic
      plants inoculated with TYLCV and CMV presented a high level of tolerance, those
      inoculated with GVA and TMV were susceptible. The amounts of virus in tolerant
      transgenic plants was lower by three orders of magnitude than those in non
      transgenic plants; in comparison, the amounts of virus in susceptible transgenic
      plants were similar to those in non-transgenic plants. Leaf extracts of the
      tolerant plants contained GroEL-virus complexes. Hence, tolerance was correlated
      with trapping of viruses in planta. This study demonstrated that multiple
      resistances to viruses belonging to several different taxonomic genera could be
      achieved. Moreover, it might be hypothesized that plants expressing GroEL will be
      tolerant to those viruses that bind to GroEL in vitro, such as members of the
      genera Begomovirus, Cucumovirus, Ilarvirus, Luteovirus, and Tospovirus.

PMID- 19184339
TI  - Porcine reproductive and respiratory syndrome viruses predominant in southeastern
      China from 2004 to 2007 were from a common source and underwent further
      divergence.
AB  - The full-length glycoprotein 5 (GP5) gene and a partial nonstructural protein 2
      (NSP2) gene fragment of 46 porcine reproductive and respiratory syndrome viruses
      (PRRSV) from pig farms in southeastern China between 2004 and 2007 were sequenced
      for phylogenetic analysis. All of the PRRSV isolates in this study were of the
      North American type, and the majority of them were clustered in subgroup II and
      had 84.1-89.1% amino acid sequence identity to those of subgroup I including the
      North American strain VR-2332. Three variable regions containing epitopes A and B
      in the N-terminal region were identified and found to be under positive
      selection. Several additional mutations, which were also located in the variable
      regions, were seen in isolates from the years 2006 and 2007 in subgroup II, as
      compared with those of earlier years (2004-2005) in the same group. Further
      analysis revealed that the majority of the subgroup II PRRSV isolates prevalent
      in the region since 2004 had thirteen mutation sites that distinguished them from
      subgroup I strains, indicating a possible introduction of a certain strain from
      the same source in the region or elsewhere well before 2004. A 29-aa deletion in
      the NSP2 fragment was found in PRRSV isolates as early as in 2005, one year
      earlier than the virulent PRRSV with the same deletion became dominant in China.
      Taken together, this study shows that subgroup II PRRSV strains with a partial
      deletion of nsp2 are currently prevailing in southeastern China.

PMID- 19184340
TI  - Genetically distinct strains of Cassava brown streak virus in the Lake Victoria
      basin and the Indian Ocean coastal area of East Africa.
AB  - Six isolates of Cassava brown streak virus (CBSV, genus Ipomovirus; Potyviridae)
      from the Lake Victoria basin in Uganda and Tanzania were characterized. Virus
      particles were 650 nm long. The complete coat protein (CP)-encoding sequences
      (1,101 nucleotides, nt) were 90.7-99.5 and 93.7-99.5% identical at the nt and
      amino acid (aa) levels, respectively. The 3' untranslated region was 225, 226 or
      227 nt long. These eight isolates were only 75.8-77.5% (nt) and 87.0-89.9% (aa)
      identical when compared to the partial CP sequences (714 nt) of six CBSV isolates
      characterized previously from the costal lowlands of Tanzania and Mozambique.
      Hence, two genetically different and geographically separated populations of CSBV
      exist in East Africa.

PMID- 19184341
TI  - Proteomic analysis reveals altered expression of proteins related to glutathione
      metabolism and apoptosis in the small intestine of zinc oxide-supplemented
      piglets.
AB  - Zinc is an important dietary factor that regulates intestinal amino acid and
      protein metabolism in animals. Recent work with the piglet, an established animal
      model for studying human infant nutrition, has shown that supplementing high
      levels of zinc oxide (ZnO) to the diet ameliorates weaning-associated intestinal
      injury and growth retardation. However, the underlying mechanisms are largely
      unknown. This study tested the hypothesis that zinc supplementation affects
      expression of proteins related to glutathione metabolism and oxidative stress in
      the gut. Using two-dimensional gel electrophoresis and mass spectrometry, we
      identified 22 up-regulated and 19 down-regulated protein spots in the jejunum of
      weanling piglets supplemented with ZnO (3,000 mg/kg Zn) compared with the control
      pigs (100 mg/kg Zn). These proteins are related to energy metabolism (increased
      level for succinyl-CoA transferase and decreased level for creatine kinase M
      type); oxidative stress (decreased levels for 78 kDa glucose-regulated protein
      and glutathione-S-transferase-omega); and cell proliferation and apoptosis
      (increased levels for A-Raf-1 and calregulin). Consistent with the changes in
      protein expression, the ratio of reduced glutathione to oxidized glutathione was
      increased, whereas glutathione-S-transferase and glutathione peroxidase
      activities as well as the protein level of active caspase-3 were reduced in ZnO
      supplemented piglets. Collectively, these results indicate that ZnO
      supplementation improves the redox state and prevents apoptosis in the jejunum of
      weaning piglets, thereby alleviating weaning-associated intestinal dysfunction
      and malabsorption of nutrients (including amino acids).

PMID- 19184342
TI  - Alimentary proteins, amino acids and cholesterolemia.
AB  - Numerous data from both epidemiological and experimental origins indicate that
      some alimentary proteins and amino acids in supplements can modify the blood LDL
      cholesterol, HDL cholesterol and total cholesterol. After an initial approval of
      the health claim for soy protein consumption for the prevention of coronary heart
      disease, more recently it has been concluded from an overall analysis of
      literature that isolated soy protein with isoflavones only slightly decrease LDL
      and total cholesterol. Other plant extracts and also some proteins from animal
      origin have been reported to exert a lowering effect on blood cholesterol when
      compared with a reference protein (often casein). The underlying mechanisms are
      still little understood. Individual amino acids and mixture of amino acids have
      also been tested (mostly in animal studies) for their effects on cholesterol
      parameters and on cholesterol metabolism. Methionine, lysine, cystine, leucine,
      aspartate and glutamate have been tested individually and in combination in
      different models of either normo or hypercholesterolemic animals and found to be
      able to modify blood cholesterol and/or LDL cholesterol and/or HDL cholesterol.
      It is however not known if these results are relevant to human nutrition.

PMID- 19184343
TI  - Antenatal psychosocial assessment: how accurate are we in determining 'low-risk'
      status? A pilot study.
AB  - Routine Comprehensive Psychosocial Assessment was implemented antenatally at a
      public hospital in Sydney in 2000. The assessment, completed on all women,
      classifies them as (1) currently, or at high-risk of becoming, distressed, or,
      (2) not currently, or at low risk of becoming, distressed during the perinatal
      period. This pilot study followed up a sample of women (N = 50) from the latter
      group at 6 weeks postpartum to explore the accuracy of 'low risk' identification.
      All but one woman reported that they continued to do well during their pregnancy.
      By 6 weeks postpartum only one woman scored high on the validated depression
      measure though data from a semi-structured interview indicated that a further
      four women experienced sub-clinical difficulty in the early weeks postpartum. The
      antenatal classification of women as 'low risk' using this assessment method
      appears to be substantially accurate, though this finding needs to be replicated
      in a larger study.

PMID- 19184344
TI  - The histamine H4 receptor antagonist JNJ7777120 induces increases in the
      histamine content of the rat conjunctiva.
AB  - OBJECTIVES: Although the H(4) receptor localisation in the eye is unresolved,
      this study aimed to investigate the effects of the H(4) receptor antagonist
      JNJ7777120 in a model of experimental conjunctivitis. METHODS: JNJ7777120, at
      0.005-1 mmol/l, was instilled into the lower conjunctival fornix of normal and
      compound 48/80 (C48/80)-challenged eyes of male Wistar rats, in the absence or
      presence of 40 mg/ml disodium cromoglycate (DSCG). Conjunctival histamine content
      was quantified 20 min post-challenge. Statistical analyses were performed by
      ANOVA. RESULTS: JNJ7777120 increased dose-dependently (r = 0.784, p < 0.001) the
      conjunctival histamine content. In the C48/80-challenged eye no effect of the
      antagonist was observed. Co-administration of JNJ7777120 with DSCG resulted in a
      biphasic action of JNJ7777120, implying a competitive action of the two agents.
      CONCLUSIONS: These data suggest a functionality of the H(4) receptor in the rat
      eye and address questions on the localization and the role of the receptor in
      ocular inflammation.

PMID- 19184345
TI  - IL-10 administration attenuates pulmonary neutrophil infiltration and alters
      pulmonary iNOS activation following hemorrhagic shock.
AB  - OBJECTIVE AND DESIGN: Several studies report immuno-modulatory effects of
      endogenous IL-10 after trauma. This study investigates the effect of IL-10
      administration on systemic and pulmonary inflammation in hemorrhagic shock.
      MATERIAL AND METHODS: Male C57/BL6 mice (4-6 animals per group) were subjected to
      volume controlled hemorrhagic shock for 3 hrs followed by resuscitation. Animals
      were either subcutaneously injected with 0.9 % saline (Shock group) or with
      recombinant mouse IL-10 (Shock+IL-10 group) 1 h before and 1 h after the
      induction of hemorrhagic shock. Serum TNF-alpha, IL-6, and keratinocyte (KC)
      concentrations were measured with the Luminex multiplexing platform. Acute
      pulmonary inflammation was assessed by pulmonary myeloperoxidase (MPO) and
      inducible nitric oxide synthase (iNOS) activity. RESULTS: IL-10 administration
      significantly decreased serum TNF-alpha (10.30 +/- 1.68 vs 37.42 +/- 10.64; p <
      0.05), IL-6 (44.22 +/- 6.65 vs 85.24 +/- 7.94; p < 0.05), and KC (276.74 +/-
      52.67 vs 465.61 +/- 58.98; p < 0.05) levels following hemorrhagic shock. Further,
      pulmonary MPO activity was significantly lower (2698.85 +/- 431.10 vs 4580.67 +/-
      294.38; p < 0.05) and pulmonary iNOS activity upregulated. CONCLUSION: These
      findings suggest that administration of IL-10 modulates the degree of hemorrhage
      induced systemic and pulmonary inflammation and support the notion of a central
      role for iNOS in acute lung injury.

PMID- 19184346
TI  - Proteinase activated receptor (PAR) involvement in mediating arthritis pain and
      inflammation.
AB  - Proteinase activated receptors (PARs) are a newly identified family of G-protein
      coupled receptors that are activated by proteinases released into tissues during
      inflammation. Evidence has accumulated which shows that PARs can exhibit both
      anti- and pro-inflammatory properties in different organ systems. During
      arthritis, proteinases are known to be released into the joint where they
      orchestrate tissue remodelling and degeneration. By activating PARs, these
      proteinases have the potential to modulate joint inflammation and pain by a
      highly targeted and selective receptor pathway. The recent identification of PARs
      on synovial fibroblasts, neutrophils, macrophages and mast cells is further
      evidence that this intriguing family of receptors could play a role in the
      pathogenesis and symptoms of arthritis. This review article provides an overview
      of the current knowledge regarding PARs and their emerging role in arthritis.

PMID- 19184347
TI  - Inhibition of neutrophil infiltration by a malleable protein matrix of lactic
      acid bacteria-fermented whey proteins in vivo.
AB  - OBJECTIVE: A novel nutraceutical ingredient, the Malleable Protein Matrix (MPM),
      has previously demonstrated a significant anti-inflammatory effect in a systemic
      inflammatory disease model, comparable to conventional drugs. The objective of
      this study was to investigate the potential anti-inflammatory effects of MPM on
      neutrophil infiltration in vivo, phagocytosis activity as well as cytokine and
      chemokine production. METHODS: Groups of ten C57BL?6J mice received water or MPM
      per os for a period of 2 weeks prior to the creation of a murine air pouch. The
      subsequent neutrophil recruitment and activities were characterized following
      lipopolysaccharide injection. RESULTS: In the water control group, the number of
      recruited cells was 1.8X10(7) cells/pouch, which was reduced to 9X10(6)
      cells/pouch with oral MPM consumption, representing an inhibition of 50% of
      infiltrating leukocytes. A considerable reduction in the cytokine and chemokine
      production, mostly TNFalpha, IL-1beta and IL-6 production in the MPM-treated
      group, suggested an inhibition of the mediators responsible for leukocyte
      extravasation. On the other hand, MPM consumption had no effect on neutrophil
      phagocytosis activity. CONCLUSION: MPM administration demonstrates a significant
      reduction of neutrophil infiltration associated with an inhibition of cytokine
      and chemokine production. The air pouch model shares similarities with in vivo
      characteristics of rheumatoid arthritis and neutrophilic diseases, both of which
      would benefit from this 50% inhibition of neutrophil infiltration induced by MPM.

PMID- 19184348
TI  - Interleukin 10 promoter region polymorphisms in inflammatory bowel disease in
      Tunisian population.
AB  - OBJECTIVE: To test whether IL-10 promoter region polymorphisms are associated
      with susceptibility to inflammatory bowel disease, we examined the contribution
      of interleukin- 10 (IL-10) gene polymorphisms to Crohn's disease (CD) and
      Ulcerative colitis disease (UC) occurrence and also to CD phenotype. MATERIELS
      AND METHODS: SNPs at positions -627 (C > A) and -1117 (G > A) in the IL-10
      promoter were determined in a sample of 105 Tunisian patients with IBD (75 CD and
      30 UC) and 90 matched healthy controls. RESULTS: The 627 CA genotype is
      associated with ileal location (p = 0.015) and with stricturing (p = 510-3) and
      penetrating (p = 310-3) presentation of CD. An additive effect between IL10
      variants and CARD15 3020 insC mutation (p = 0,006) on severe forms of CD was
      shown. CONCLUSIONS: In Tunisian population, the 3020insC insertion in NOD2/CARD15
      gene is a marker of susceptibility to CD, while the A allele at position -627 in
      the IL-10 promoter increases the risk of CD ileal location and severe disease
      presentation. A genetic epistasis between IL-10 gene polymorphisms and
      CARD15/NOD2 gene mutation was suggested.

PMID- 19184349
TI  - Individual behavioral differences in recovery from abdominal sepsis in rats.
AB  - OBJECTIVE AND DESIGN: In the present study we determined whether individual
      behavioral differences (high and low locomotor activity) differentially affected
      recovery from sepsis with high or low mortality. METHODS: Two trials were
      performed. Trial 1 with high mortality: Rats were randomly assigned to (1)
      control-A: anesthesia, (2) control-B: sham surgery, (3) sepsis: laparotomy and
      peritoneal contamination and infection (PCI) with human stool bacteria, (4)
      sepsis with antibiotic prophylaxis (cefuroxime/ metronidazole), and (5) sepsis
      with antibiotic plus G-CSF prophylaxis. Trial 2 with low mortality: Comparison of
      groups 3 and 5. Endpoints were mortality, behavior (open field and social
      interaction tests), and proinflammatory cytokines (interleukin-6 = IL-6 and
      macrophage inflammatory protein-2 = MIP-2). RESULTS: The combination of
      antibiotics plus G-CSF was most effective in reducing mortality in both trials
      and modified sickness behavior. Behavioral deficits were not statistically
      significantly improved by G-CSF. However, high versus low responders were
      differentially affected in both behavioral tests. Furthermore, IL-6 and MIP-2
      were increased 24 hours after inoculum only in high responders with untreated
      sepsis and high mortality. CONCLUSION: Improvement of sickness behavior in sepsis
      with G-CSF/antibiotic prophylaxis is a promising approach. The course of recovery
      from sepsis may depend on premorbid individual differences.

PMID- 19184350
TI  - 3020insC insertion in NOD2/CARD15 gene, a prevalent variant associated with anti
      Saccharomyces cerevisiae antibodies and ileal location of Crohn's disease in
      Tunisian population.
AB  - OBJECTIVE: Our aim is to investigate the relation between CARD15 3020insC
      mutation, anti-Saccharomyces cerevisiae antibodies (ASCA) and disease phenotype,
      in Tunisian inflammatory bowel disease (IBD) patients. MATERIALS: A hundred
      Tunisian patients with IBD (75 Crohn's disease CD and 25 ulcerative colitis UC)
      and 60 matched healthy controls were studied. METHODS: CARD15 mutation was
      analysed by using an allele-specific polymerase chain reaction and sequencing.
      Assessment of ASCA in serum was performed by ELISA. RESULTS: The frequency of the
      mutation was significantly higher in Crohn's disease than in control (p = 0,0005;
      OR = 20.45; CI 95% = 2.86-413.85) and did not differ statistically in UC group (p
      = 0, 05) from control. ASCAs were present in 60% of CD and 20, 8% of UC.
      CONCLUSION: This study suggests that in northern Tunisian population, 3020insC
      mutation in NOD2/CARD15 gene is a prevalent mutation leading to the typical
      Crohn's disease including ileal location, stricturing and penetrating clinical
      types and ASCA expression.

PMID- 19184351
TI  - The effect of adjunctive chlorhexidine mouthrinse on clinical parameters and
      gingival crevicular fluid cytokine levels in untreated plaque-associated
      gingivitis.
AB  - OBJECTIVE AND DESIGN: To examine the effectiveness of chlorhexidine mouthrinse
      (CHX) in addition to daily plaque control on gingival inflammation. METHODS:
      Fifty gingivitis patients were randomized to CHX or placebo groups. In addition
      to proper plaque control, CHX group rinsed with CHX, while placebo group rinsed
      with placebo mouthrinse for 4 weeks. Gingival crevicular fluid (GCF) samples were
      collected and clinical parameters including plaque index (PI), papillary bleeding
      index (PBI), calculus index and probing depth (PD) were recorded at baseline and
      repeated at 4 week. GCF IL-1alpha, IL-1beta, IL-1Ra, and IL-8 levels were
      determined by ELISA. RESULTS: Whole mouth clinical parameters were significantly
      improved in both groups at 4 weeks. CHX group showed greater reduction in the
      mean PI scores than placebo at 4 weeks (p < 0.05). GCF IL-8 levels of anterior
      sites significantly reduced in CHX and placebo group at 4 weeks (p < 0.05). GCF
      IL-1alpha, IL-1beta, IL-1Ra levels remained unchanged at 4 weeks in both groups.
      GCF cytokine levels of CHX group were similar to those of placebo at 4 weeks.
      CONCLUSIONS: Within the limitations of this study, CHX mouthrinse as adjuncts to
      daily plaque control could be useful in management of plaque-associated
      gingivitis, although ineffective on GCF cytokine levels.

PMID- 19184352
TI  - Concentrations of alpha- and beta-defensins in plasma of patients with
      inflammatory bowel disease.
AB  - BACKGROUND: Impaired production/release of defensins, representative endogenous
      antimicrobial peptides, is associated with the pathogenesis of inflammatory bowel
      disease (IBD). MATERIAL AND METHODS: Employing in house radioimmunoassay, we
      examined concentrations of the major forms alpha-defensins, human neutrophil
      peptides (HNP) 1-3 and human beta-defensin (HBD)-2 in plasma of 55 IBD patients
      consisting of 29 patients with ulcerative colitis (UC) and 26 with Crohn's
      disease (CD) and 57 controls. RESULTS: The circulating HNP 1-3, but not HBD-2,
      levels in IBD patients were significantly higher than those in controls. Plasma
      HNP 1-3 concentrations in CD patients significantly correlated with Crohn's
      disease activity index, peripheral white blood cell counts, serum CRP values and
      TNF-alpha levels. CONCLUSIONS: Elevation of circulating alpha-defensins levels is
      suggestive of their physiopathological roles in IBD. Plasma HNP 1-3
      concentrations may be an indicator for CD activity and their association with CRP
      and TNF-alpha supports a possible association with the inflammatory process.

PMID- 19184353
TI  - Bioelimination of histamine in epithelia of the porcine proximal colon of pigs.
AB  - OBJECTIVE: The study aimed to gain insight into how intestinal histamine N
      methyltransferase (HMT) and diamine oxidase (DAO) could contribute to
      bioelimination of histamine. MATERIAL AND METHODS: Mucosal-to-serosal (ms) and
      serosal-to-mucosal (sm) fluxes of histamine, choline or 5-hydroxytryptamine were
      measured in isolated colonic epithelia of pigs (Ussing chambers). RESULTS:
      Radioactively (hist-rad) and HPLC-measured histamine fluxes were higher in sm vs.
      ms direction at 100 microM histamine. Choline (3-3000 microM) and 5-HT (20
      microM) fluxes only tended to be higher in sm vs. ms direction. Secretion of hist
      rad was abolished by serosal 1-methyl-4-phenylpyridinium (MPP). Histamine fluxes
      accounted for <25 % of hist-rad fluxes, but this percentage increased after
      blocking HMT (100 microM amodiaquin) or DAO (100 microM aminoguanidine). 1
      Methylhistamine (1-MH) appeared exclusively in the serosal medium. 1-MH
      appearance decreased after addition of amodiaquin or after addition of N
      ethylmaleimide (1 mM NEM). Blockage of vesicular trafficking by NEM enhanced
      histamine catabolism, which could be reversed by aminoguanidine. DAO was detected
      in punctuate structures in the basal parts of colonocytes by
      immunohistochemistry. CONCLUSIONS: A basolateral organic cation transporter
      facilitates histamine secretion into the intestinal lumen and delivers histamine
      to catabolism by HMT and/or vesicular DAO. Histamine is partially released back
      into the blood after initial biotransformation to 1-MH.

PMID- 19184354
TI  - Leukotrienes C4 and D4 sensitize human neutrophils for hyperreactivity to
      chemoattractants.
AB  - OBJECTIVE AND DESIGN: To investigate the sensitizing effects of the cysteinyl
      leukotrienes (CysLTs) C(4) and D(4) on the proinflammatory responses of
      chemoattractant-activated human neutrophils in vitro. MATERIALS: Neutrophils were
      isolated from venous blood taken from healthy, adult, human volunteers.
      TREATMENT: Cells were exposed to LTC(4) and LTD(4) (50-300 nM) prior to
      activation with 1 microM of N-formyl-L-methionyl- L-leucyl-L-phenylalanine
      (fMLF). METHODS: A fura-2/AM-based spectrofluorimetric procedure, lucigenin
      enhanced chemiluminescence (LECL), a colourimetric method and an ELISA procedure,
      were used to measure Ca(2+) mobilization, superoxide production, elastase and MMP
      8 release respectively following activation of LTC(4)/ D(4)-primed neutrophils
      with fMLF. Superoxide generation was also measured in the presence and absence of
      the CysLT receptor 1 antagonist, montelukast (100 nM). RESULTS: Exposure of
      neutrophils to either LTC(4) or LTD(4) alone had modest effects on Ca(2+)
      mobilization, while superoxide generation and elastase release were unaffected.
      However, relative to the responses of neutrophils activated with fMLF in the
      absence of the CysLTs, pre-treatment of the cells with either LTC(4)or LTD(4)
      resulted in significant, augmentation of fMLF-activated elastase and MMP-8
      release and superoxide generation, which was attenuated by montelukast.
      CONCLUSION: These previously undocumented sensitizing interactions of LTs C(4)
      and D(4) with neutrophils may contribute to the activation of these cells in
      acute and chronic inflammation of both atopic and non-atopic aetiology, while
      identifying a role for montelukast in regulating neutrophil reactivity.

PMID- 19184355
TI  - Widespread expression of inducible NOS and citrulline in lupus nephritis tissues.
AB  - OBJECTIVE: Examine the presence of functional inducible nitric oxide synthase
      (iNOS) in lupus nephritis lesions. METHODS: Seventeen kidney biopsies from
      patients with lupus nephritis and an equal number of normal control kidney
      biopsies were examined for the presence of iNOS and endothelial nitric oxide
      synthase (eNOS) and citrulline by using immunohistochemical methods.
      Additionally, iNOS and eNOS mRNAs were examined by reverse transcription -PCR
      amplification of total renal RNA. RESULTS: All biopsies expressed constitutive
      eNOS, but in contrast to normal kidney biopsies, 70% of the lupus biopsies also
      expressed iNOS mRNA and the cognate protein. Eight positive biopsies corresponded
      to class IV lupus nephritis, which also had a high degree of citrullination.
      CONCLUSIONS: The data indicate that functional iNOS activity is present in
      glomeruli as part of the inflammatory process in the kidney; therefore the
      products of iNOS could play a role in the pathogenesis of lupus nephritis.

PMID- 19184356
TI  - Downregulating osteopontin reduces angiotensin II-induced inflammatory activation
      in vascular smooth muscle cells.
AB  - OBJECTIVE: Atherosclerosis is considered as a chronic inflammatory response in
      arterial blood vessels. The function of osteopontin (OPN), a proinflammatory
      cytokine, in the Ang II-induced inflammatory activation in vascular smooth muscle
      cells (VSMCs) remains poorly understood. METHODS: In the present study, the role
      of OPN was investigated by knocking down OPN using small interfering RNA (siRNA).
      VSMCs from human saphenous vein were divided into three groups according to RNAi
      treatment: OPN siRNA group, sham (un-transfected) treated group, and control
      siRNA group. RNAi effect was investigated by real time PCR, western blotting
      analysis and ELISA. Then all groups were stimulated with Ang II. The inflammatory
      activation was assessed by determining the activation of NFkappaB and activator
      protein-1 (AP-1), and the release of interleukin-6 (IL-6) and IL-1beta. RESULTS:
      OPN was knocked down effectively in OPN RNAi group. Inflammatory activations,
      such as NFkappaB and AP-1 activation and IL-6 accumulation, were induced by Ang
      II in sham treated group and control siRNA group. However, it was abolished in
      OPN siRNA group by the downregulation of OPN compared to sham treated group and
      control siRNA group. CONCLUSIONS: This result suggested that OPN plays an
      important role in Ang II-induced inflammatory activation in VSMCs. The finding
      further supports OPN as a potential target for atherosclerotic therapy.

PMID- 19184357
TI  - Temporal expression of cyclooxygenase-2 in peritoneal macrophages of rats and
      effects of panax notoginseng saponins.
AB  - OBJECTIVE: To explore the temporal expression pattern of cyclooxygenase (COX)-2
      and effects of panax notogensing saponins (PNS) in peritoneal macrophages of
      rats. MATERIALS AND METHODS: Phagocytosis function of peritoneal macrophages was
      measured by chicken red blood cell phagocytosis assay in vitro. Expression of COX
      2 mRNA and protein, PGE(2) and PGD(2) production were determined with real-time
      PCR, Western blotting and radioimmunoassay, respectively. RESULTS: Phagocytosis
      function of macrophages increased significantly after stimulation and reached
      peak during 2-3h. Expression of COX-2 mRNA and its protein increased markedly
      after stimulation and reached the first peak at 2 h and 3h, respectively; and
      then decreased to reach a minimum at 24h. The second peak appeared at 36h. PNS
      (50, 100, 200 mg/kg) increased the phagocytosis function obviously at 2h,
      decreased the expression level of COX-2 and PGE(2) production at 2 h and elevated
      COX-2 expression and PGD(2) production at 36 h, respectively. CONCLUSION: COX-2
      expression in peritoneal macrophages has a double-hump feature after stimulation.
      PNS enhanced phagocytosis, inhibiting COX-2 expression at an early stage and
      elevating it at a later stage.

PMID- 19184358
TI  - Protective effect of retinoid against endotoxin-induced mastitis in rats.
AB  - OBJECTIVE: A lipopolysaccharide (LPS) induced mastitis model in rats was used to
      study the protective effect of retinoid. MATERIALS AND METHODS: Commencing at
      gestation day 10, retinoid (dissolved in olive oil) or an equal volume of olive
      oil was administered to rats daily by gavage until parturition. LPS or pyrogen
      free physiological saline was inoculated into the mammary gland 72h after
      parturition and the rats were euthanized at 12h post-infection. RESULTS:
      Myeloperoxidase (MPO), N-acetyl -beta-D- glucosaminidase (NAGase), tumor necrosis
      factor-alpha (TNF-alpha), interleukin-8 (IL-8) in mammary tissues and
      CD4(+)/CD8(+) in peripheral blood were increased and serum MPO and IL-2 in
      mammary tissues were decreased 12h after LPS infusion. Retinoid decreased MPO,
      NAGase, and TNF-alpha in mammary tissue and increased IL-2 in serum. Four
      thousand and 8000 I.U/kg x d of retinoid significantly decreased the infiltration
      of PMNs in mammary alveoli and ameliorated the imbalance of CD4+/CD8+ in
      peripheral blood. CONCLUSION: These results suggest that retinoid protected
      against LPS-induced mastitis in a rat model.

PMID- 19184359
TI  - Serum-induced macrophage activation is related to the severity of septic shock.
AB  - BACKGROUND: It seems that a balance between anti and pro-inflammatory responses
      must be kept to eliminate the pathogen without inducing inflammatory damage in
      the host. Thus we determined the relation between macrophage activation and the
      severity and clinical outcome in septic patients. MATERIAL AND METHODS: This was
      a prospective study at a tertiary general intensive care unit. Thirty-three
      patients admitted with sepsis, severe sepsis or septic shock were included. As a
      control group, healthy volunteers were included matched to septic patients by age
      and sex. Peritoneal rat macrophages were cultured with 2% serum from healthy
      volunteers or from septic patients for determination of phagocytic potential or
      the capacity to produce cytokines. RESULTS: TNF and IL1 secretion by macrophages
      activated with serum from sepsis and severe sepsis patients was higher than with
      serum from healthy controls. In addition, proinflammatory cytokines released in
      vitro from macrophages, but not determined directly in the serum from patients,
      were lower in non-survivor septic patients when compared to survivors. In
      contrast, IL-10 secretion by macrophages activated with serum from septic
      patients was higher in nonsurvivors. In the septic shock group we observed a
      diminution in the phagocytic index compared to sepsis and severe sepsis groups,
      and the phagocytic index was higher in sepsis survivors. CONCLUSIONS: Markers of
      antiinflammation are predominant in more severe types of sepsis suggesting that
      antiinflammation is related to mortality.

PMID- 19184360
TI  - Kinetic and pharmacological properties of [(3)H]-histamine transport into
      cultured type 1 astrocytes from neonatal rats.
AB  - OBJECTIVE AND DESIGN: Astrocytes actively participate in the inactivation of
      neurotransmitters. In this work we elucidated the contribution of astrocytes in
      clearance of histamine, a process which has not yet been fully clarified.
      METHODS: The characteristics of [(3)H]-histamine uptake were determined in
      cultured neonatal rat type 1 astrocytes and histamine-N-methyl-transferase
      expression was determined using RT-PCR. RESULTS: These cells transport [(3)H]
      histamine in a time- and concentration-dependent manner. The histamine clearance
      by astrocytes was described by a mathematical model including two processes:
      electrodiffusion and active transport. A further analysis of kinetic parameters
      of a carrier-operated transport revealed a single transport system with Michaelis
      constant (K(m)) of 3.5 +/- 0.8 microM and a maximal uptake rate (V(max)) of 7.9
      +/- 0.3 pmol/mg protein/min. From drugs tested amitriptyline, desipramine,
      mepyramine and cimetidine significantly decreased [(3)H]-histamine uptake. Taken
      up histamine could be metabolically degraded in cultured astrocytes, since they
      express mRNA for enzyme histamine-N-methyltransferase. CONCLUSIONS: Astrocytes
      participate in the clearance of extracellular histamine by electrodiffusion and
      active transport by a yet not identified carrier. Taken up histamine can be
      converted to tele-methylhistamine within astrocytes thus indicating the
      involvement of astrocytes not only in clearance but also in the inactivation of
      histamine.

PMID- 19184361
TI  - Evidence that 13-14 di-hydro, 15-keto prostaglandin D(2)-induced airway
      eosinophilia in guinea-pigs is independent of interleukin-5.
AB  - OBJECTIVE AND DESIGN: Prostaglandin D(2) (PGD(2)) has been shown to cause
      eosinophil, basophil and Th2 cell chemotaxis in vitro and in vivo through an
      action on the prostaglandin CRTH2 receptor. In the present study, the dependence
      of PGD(2)-induced eosinophil accumulation in vivo on interleukin-5 (IL-5) blood
      eosinophilia was investigated. MATERIALS: Guinea-pigs were exposed to aerosols of
      13,14di-hydro 15-keto PGD(2) (DK-PGD(2)) or platelet activating factor (PAF) and
      the eosinophil content of the bronchoalveolar lavage fluid or blood determined.
      In some experiments, DK-PGD(2) was administered systemically and eosinophilia
      measured. RESULTS: Aerosols of DK-PGD(2) caused eosinophil accumulation in the
      lungs 24h after exposure. DK-PGD(2) (10 microg x ml(-1)) -induced airway
      eosinophilia was inhibited when animals were treated with the CRTH2 receptor
      antagonist ramatroban. 1-4h after exposure to DK-PGD(2) a significant decrease in
      blood eosinophil count was measured. The anti-IL-5 antibody TRFK-5 had no
      inhibitory effect of DK-PGD(2)-induced airway eosinophilia, but abolished airway
      eosinophilia induced by exposure of guinea-pigs to aerosols of PAF. Intracardiac
      injection of DK-PGD(2) induced a dose-related increase in blood eosinophil
      numbers. CONCLUSIONS: It is concluded that, in the guinea-pig, DK-PGD(2)-induced
      airway eosinophilia is mediated by an action on prostaglandin CRTH2 receptors and
      that this response appears to be independent of IL-5.

PMID- 19184362
TI  - Combination therapies that inhibit cyclooxygenase-2 and leukotriene synthesis
      prevent disease in murine collagen induced arthritis.
AB  - OBJECTIVE AND DESIGN: To determine the effect of combinations of cyclooxygenase
      (COX) inhibitors and inhibitors of leukotriene (LT) syntheses on collagen induced
      arthritis (CIA) in mice. METHODS: The CIA model was evaluated for the presence of
      eicosanoids in the paw tissue. Several selective cyclooxygenase 2 (COX-2)
      inhibitors or non-selective non-steroidal anti inflammatory drugs (NSAIDs) were
      evaluated alone or in combination with leukotriene (LT) synthesis inhibitors in
      the CIA model. RESULTS: Arthritic paw tissue showed increased levels of
      prostaglandins and leukotrienes in comparison to normal paws. Analysis of mRNA
      levels indicated the inducible form of the COX-2 enzyme to be the source of
      prostaglandins. NSAIDs, COX-2 or leukotriene synthesis inhibitors administered
      alone in CIA decreased severity but had little effect on disease incidence.
      However, the combination of selective COX-2 inhibitors with leukotriene synthesis
      inhibitors produced significant decreases in both incidence and severity,
      suggesting an additive or synergistic effect. This effect was reversible with
      removal of drug. Little decrease in incidence was observed with the NSAID/5-LO
      inhibitor combinations. CONCLUSIONS: These results suggest that the induction of
      the disease in CIA is mediated by products of the COX-2 enzyme and LTB4
      production, and that blockade of both pathways is required to prevent CIA.

PMID- 19184363
TI  - Hemostasis and thrombosis in older adults.

PMID- 19184364
TI  - Thrombogenesis in atrial fibrillation contributing mechanisms and natural
      history.

PMID- 19184365
TI  - Glycine- and proline-rich glycoprotein regulates the balance between cell
      proliferation and apoptosis for ACF formation in 1,2-dimethylhydrazine-treated
      A/J mice.
AB  - The objective of this study was to investigate the chemopreventive potentials of
      glycine- and proline-rich glycoprotein (SNL glycoprotein, 150-kDa) isolated from
      Solanum nigrum Linne on formation of colonic aberrant crypt foci (ACF) induced by
      1,2-dimethylhydrazine (DMH, 20 mg/kg) in A/J mice. Administration of SNL
      glycoprotein inhibited phosphorylation of extracellular signal-regulated kinase
      (ERK), expression of colonic proliferating cell nuclear antigen (PCNA), and
      frequency of colonic ACF in DMH-stimulated mice colon carcinogenesis. In
      addition, SNL glycoprotein increased expression of cyclin-dependent kinase
      inhibitors (p21(WAF/Cip1) and p27(Kip1)), whereas reduced expression of precursor
      form of apoptosis-related proteins [pro-caspase-3 and pro-poly(ADP
      ribose)polymerase (PARP)] in the mice. Interestingly, the results in this study
      revealed that SNL glycoprotein has suppressive effects on activity of nuclear
      factor-kappa B (NF-kappaB), whereas it has stimulatory effect on the expression
      of p53, accompanying inhibitory effects on expression of NF-kappaBp50, inducible
      nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, and
      tumor necrosis factor (TNF)-alpha in DMH-stimulated ACF formation. Also, SNL
      glycoprotein has inhibitory effects on the formation of thiobarbituric acid
      reactive substances (TBARS), on the production of inducible nitric oxide (NO),
      and on the release of lactate dehydrogenase (LDH) in the mice plasma.
      Collectively, our findings in this study suggest that SNL glycoprotein has
      chemopreventive activity via modulation of cell proliferation and apoptosis in
      DMH-treated A/J mice.

PMID- 19184366
TI  - Analysis of quaternary structure of a [LDH-like] malate dehydrogenase of
      Plasmodium falciparum with oligomeric mutants.
AB  - L-Malate dehydrogenase (PfMDH) from Plasmodium falciparum, the causative agent
      for the most severe form of malaria, has shown remarkable similarities to L: 
      lactate dehydrogenase (PfLDH). PfMDH is more closely related to [LDH-like] MDHs
      characterized in archae and other prokaryotes. Initial sequence analysis and
      identification of critical amino acid residues involved in inter-subunit salt
      bridge interactions predict tetrameric structure for PfMDH. The catalytically
      active recombinant PfMDH was characterized as a tetramer. The enzyme is localized
      primarily in the parasites cytosol. To gain molecular insights into PfMDH/PfLDH
      relationships and to understand the quaternary structure of PfMDH, dimers were
      generated by mutation to the potential salt-bridge interacting sites. The R183A
      and R214G mutations, which snapped the salt bridges between the dimers and
      resulted in lower dimeric state, did not affect catalytic properties of the
      enzyme. The mutant dimers of PfMDH were active equally as the wild-type PfMDH.
      The studies reveal structure of PfMDH as a dimer of dimers. The tetrameric state
      of PfMDH was not essential for catalytic functions of the enzyme but may be an
      evolutionary adaptation for cytosolic localization to support its role in
      NAD/NADH coupling, an important metabolic function for survival of the malaria
      parasite.

PMID- 19184367
TI  - Cell type-specific expression of endogenous cardiac Troponin I antisense RNA in
      the neonatal rat heart.
AB  - Since the number of detected natural antisense RNA is growing, investigations
      upon the expression pattern of the antisense RNA become more important. As we
      focused our work on natural occurring antisense transcripts in human and rat
      heart tissues, we were interested in the question, whether the expression pattern
      of antisense and sense RNA can vary in different cell types of the same tissue.
      In our previous analysis of total neonatal rat heart tissue, we demonstrated the
      co-expression of both cTnI RNA species in this tissue. Now we investigated the
      expression of antisense and sense RNA quantitatively in neonatal cardiomyocytes
      (NCMs) and neonatal cardiac fibroblasts (NCFs). Performing northern blot as well
      as RT-PCR, we could detect natural antisense and sense RNA transcripts of cTnI in
      NCM and NCF implying that these transcripts are co-expressed in both cell types.
      The absolute amounts of the RNA transcripts were higher in NCM. Both RNA species
      showed identical sizes in the northern blot. Quantification by real-time PCR
      revealed a higher relative level of natural antisense RNA in NCF compared to NCM
      which points out to a cell type-specific expression of sense and antisense RNA.
      Our observations suggest that antisense RNA transcription may contribute to a
      cell type-specific regulation of the cTnI gene.

PMID- 19184368
TI  - ZAK induces MMP-2 activity via JNK/p38 signals and reduces MMP-9 activity by
      increasing TIMP-1/2 expression in H9c2 cardiomyoblast cells.
AB  - Leucine-zipper and sterile-alpha motif kinase (ZAK) is the key intra-cellular
      mediator protein in cardiomyocyte hypertrophy induction by transforming growth
      factor beta 1 (TGF-beta1) which has also been identified as a profibrotic
      cytokine involved in cardiac fibrosis progression. We hypothesized whether ZAK
      over-expression causes cardiac scar formation due to the extra-cellular matrix
      (ECM) degraded enzyme regulation in this paper. Using immuno-histochemical
      analysis of the human cardiovascular tissue array, we found a positively
      significant association between ZAK over-expression and myocardial scars. ZAK
      over-expression in H9c2 cardiomyoblast cells increases the metalloproteinase
      tissue inhibitor 1/2 (TIMP-1/2) protein level, which reduces matria
      metalloproteinase-9 (MMP-9) activity and also activates c-JNK N-terminal kinase
      1/2 (JNK1/2) and p38 signaling, which induces MMP-2, possibly resulting in
      cardiac fibrosis. Taken together, ZAK activity inhibition may be a good strategy
      to prevent the cardiac fibrosis progression.

PMID- 19184369
TI  - Lipopolysaccharide upregulates uPA, MMP-2 and MMP-9 via ERK1/2 signaling in H9c2
      cardiomyoblast cells.
AB  - Upregulation of urokinase plasminogen activator (uPA), tissue plasminogen
      activator (tPA), and matrix metallopeptidases (MMPs) is associated with the
      development of myocardial infarction (MI), dilated cardiomyopathy, cardiac
      fibrosis, and heart failure (HF). Evidences suggest that lipopolysaccharide (LPS)
      participates in the inflammatory response in the cardiovascular system; however,
      it is unknown if LPS is sufficient to upregulate expressions and/or activity of
      uPA, tPA, MMP-2, and MMP-9 in myocardial cells. In this study, we treated H9c2
      cardiomyoblasts with LPS to explore whether LPS upregulates uPA, tPA, MMP-2, and
      MMP-9, and further to identify the precise molecular and cellular mechanisms
      behind this upregulatory responses. Here, we show that LPS challenge increased
      the protein levels of uPA, MMP-2 and MMP-9, and induced the activity of MMP-2 and
      MMP-9 in H9c2 cardiomyoblasts. However, LPS showed no effects on the expression
      of tissue inhibitor of metalloproteinase-1, -2, -3, and -4 (TIMP-1, -2, -3, and 
      4). After administration of inhibitors including U0126 (ERK1/2 inhibitor),
      SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), CsA (calcineurin
      inhibitor), and QNZ (NFkappaB inhibitor), the LPS-upregulated expression and/or
      activity of uPA, MMP-2, and MMP-9 in H9c2 cardiomyoblasts are markedly inhibited
      only by ERK1/2 inhibitors, U0126. Collectively, these results suggest that LPS
      upregulates the expression and/or activity of uPA, MMP-2, and MMP-9 through
      ERK1/2 signaling pathway in H9c2 cardiomyoblasts. Our findings further provide a
      link between the LPS-induced cardiac dysfunction and the ERK1/2 signaling pathway
      that mediates the upregulation of uPA, MMP-2 and MMP-9.

PMID- 19184370
TI  - Differential physical, rheological, and biological properties of rapid in situ
      gelable hydrogels composed of oxidized alginate and gelatin derived from marine
      or porcine sources.
AB  - Marine derived gelatin is not known to associate with any communicable diseases
      to mammals and could be a reasonable substitute for gelatin derived from either
      bovine or porcine sources. The low melting point of marine gelatin (8 degrees C)
      also offers greater formulation flexibility than mammalian derived gelatins.
      However, the sub-optimal physical properties of marine gelatin generally limit
      the interest to further develop it for biomedical applications. This study aimed
      at investigating the feasibility of using oxidized alginate (Oalg) as a high
      activity macromolecular crosslinker of marine gelatin to formulate in situ
      gelable hydrogels with the goal of enhancing the latter's physical properties.
      The performance of Oalg/marine gelatin hydrogel was compared to Oalg/porcine
      gelatin hydrogel; in general, the physicomechanical properties of both hydrogels
      were comparable, with the hydrogels containing porcine gelatin exhibiting
      moderately higher mechanical strengths with shorter gelation times, smaller size
      pores, and higher swelling ratios. On the contrary, the biological performances
      of the two hydrogels were significantly difference. Cells cultured in the marine
      gelatin derived hydrogel grew significantly faster, with greater than 60% more
      cells by 7 days and they exhibited more spread-out conformations as compared
      those cultured in the porcine derived hydrogel. Production of ECM by cells
      cultured in the Oalg/marine gelatin hydrogel was up to 2.4 times greater than
      that of in the Oalg/porcine gelatin hydrogel. The biodegradation rate of the
      hydrogel formulated from marine gelatin was greater than its counterpart prepared
      from porcine gelatin. These differences have important implications in the
      biomedical applications of the two hydrogels.

PMID- 19184371
TI  - Bioactive borosilicate glass scaffolds: in vitro degradation and bioactivity
      behaviors.
AB  - Bioactive borosilicate glass scaffolds with the pores of several hundred
      micrometers and a competent compressive strength were prepared through
      replication method. The in vitro degradation and bioactivity behaviors of the
      scaffolds have been investigated by immersing the scaffolds statically in diluted
      phosphate solution at 37 degrees C, up to 360 h. To monitor the degradation
      progress of the scaffolds, the amount of leaching elements from the scaffolds
      were determined by ICP-AES. The XRD and SEM results reveal that, during the
      degradation of scaffolds, the borosilicate scaffolds converted to hydroxyapatite.
      The compressive strength of the scaffolds decreased during degradation, in the
      way that can be well predicted by the degradation products, or the leachates,
      from the scaffolds. MTT assay results demonstrate that the degradation products
      have little, if any, inhibition effect on the cell proliferation, when diluted to
      a certain concentration ([B] <2.690 and pH value at neutral level). The study
      shows that borosilicate glass scaffold could be a promising candidate for bone
      tissue engineering material.

PMID- 19184372
TI  - In silico prediction of drug permeability across buccal mucosa.
AB  - PURPOSE: To develop and validate a computational model capable of predicting
      buccal permeability based on various structural and physicochemical descriptors.
      METHODS: Apparent permeability coefficients (K(p)) of 15 different drugs across
      porcine buccal mucosa were determined. Multiple linear regression (MLR) and
      maximum likelihood estimations (MLE) were used to develop the model based on a
      training set of 15 drugs with permeability as the response variable and the
      various descriptors as the predictor variables. The final model was validated
      with an external data set consisting of permeability values obtained from the
      literature. RESULTS: Drug permeabilities ranged from 30 x 10(-6) (nimesulide) to
      3.3 x 10(-9) cm/s (furosemide). Regression analysis showed that 95% of the
      variability in permeability data can be explained by a model that includes
      molecular volume, distribution coefficient at pH 6.8, number of hydrogen bond
      donors, and number of rotatable bonds. Smaller molecular size, high
      lipophilicity, lower hydrogen bond capability and greater flexibility were
      important for permeability. The buccal model was found to have a good predictive
      capability. CONCLUSION: A simple model was developed and validated for predicting
      the buccal drug permeability. This model will be useful in assessing the
      feasibility of drugs for transbuccal delivery.

PMID- 19184373
TI  - Influence of ethanol on physical state of freeze-dried mannitol.
AB  - PURPOSE: The purpose of this study is to characterize freeze-dried mannitol
      prepared from an ethanol-containing solution as a function of the ethanol ratio,
      mannitol concentration, and annealing in the freeze-drying cycle. METHODS: The
      characteristics of the freeze-dried mannitol were evaluated by X-ray
      diffractometry (XRD) and differential scanning calorimetry (DSC). The
      reconstitution time was measured for the freeze-dried solids as well as the
      residual moisture and ethanol by Karl-Fischer titration and gas chromatography,
      respectively. RESULTS: The XRD pattern of 5% (w/v) mannitol freeze-dried from
      aqueous solution with no annealing cycle showed all the five characteristic peaks
      at 13.6 degrees and 17.2 degrees 2theta for the alpha polymorph, at 14.6 degrees
      and 23.4 degrees 2theta for the beta polymorph and at 9.7 degrees 2theta for the
      delta polymorph. The addition of ethanol to the initial solutions resulted in
      only a peak at 9.7 degrees 2theta, indicating the presence of only the delta
      polymorph, regardless of the ethanol ratio in the initial solutions used [10, 20,
      30, and 40% (v/v)]. However, annealing during freeze-drying influenced the XRD
      pattern; in particular, for the solid prepared from the 10% ethanol solution.
      Annealing of the 10% ethanol solution promoted the formation of the alpha
      polymorph and produced a different peak that might be attributable to another
      polymorph. In DSC thermograms, an endotherm and a subsequent exotherm were found
      in the temperature range of 150 degrees C to 160 degrees C, which corresponded to
      the transition of the delta form to alpha or beta forms. The magnitude of this
      transition was smaller as the ethanol ratio increased for the solids from ethanol
      containing solutions with an annealing cycle. In other words, annealing of the
      ethanol-containing solutions promoted delta polymorph formation in the lyophiles.
      In addition, the mannitol concentration affected the polymorphism in freeze-dried
      solids prepared from aqueous and 10% ethanol solutions. Addition of ethanol in
      the initial solution, in particular, at a lower ethanol level (10% v/v), and a
      higher concentration of mannitol could also promote the generation of lumps in
      freeze-dried solids during reconstitution, and result in longer reconstitution
      time. The residual moisture levels were less than 0.5%, and residual ethanol
      levels were less than 0.1%, irrespective of the formulation used. CONCLUSIONS:
      The physical state and reconstitution time of the freeze-dried mannitol appears
      to be a complex function of the ethanol and mannitol concentrations in the
      initial solution before freeze-drying and of annealing during the freeze-drying
      process.

PMID- 19184375
TI  - The challenge of integrated care for mental health: leaving the 50 minute hour
      and other sacred things.
AB  - A growing body of research has demonstrated the effectiveness of integrating
      mental/behavioral healthcare with primary care in improving health outcomes.
      Despite this rich literature, such demonstration programs have proven difficult
      to maintain once research funding ends. Much of the discussion regarding
      maintenance of integrated care has been focused on lack of reimbursement.
      However, provider factors may be just as important, because integrated care
      systems require providers to adopt a very different role and operate very
      differently from traditional mental health practice. There is also great
      variability in definition and operationalization of integrated care. Provider
      concerns tend to focus on several factors, including a perceived loss of
      autonomy, discomfort with the hierarchical nature of medical care and primary
      care settings, and enduring beliefs about what constitutes "good" treatment.
      Providers may view integrated care models as delivering substandard care and
      passively or actively resist them. Dissemination of available data regarding
      effectiveness of these models is essential (e.g. timeliness of treatment, client
      satisfaction). Increasing exposure and training in these models, while
      maintaining the necessary training in traditional mental health care is a
      challenge for training at all levels, yet the challenge clearly opens new
      opportunities for psychology and psychiatry.

PMID- 19184374
TI  - Intraocular sustained-release delivery systems for triamcinolone acetonide.
AB  - Recently, the use of triamcinolone acetonide (TA) injection has increased
      dramatically in treatment for several ocular diseases. Among them, macular
      diseases such as macular edema due to diabetic retinopathy, venous occlusive
      diseases, ocular inflammation and age-related macular degeneration (AMD) are very
      common vision threatening disorders and are great challenges to treat. In these
      types of chronic retinal diseases, repeated intraocular injections of TA are
      often required which increases the likelihood of complications. In order to
      achieve sustained-release, maintain therapeutic levels of TA over longer times
      and reduce frequency of intravitreal injections, researchers are investigating
      different implantable devices or injectable systems. However, as of yet, there is
      no sustained-release product for TA available on the commercial market. This
      review discusses and compares different sustained-release devices or injectable
      systems that are currently being developed.

PMID- 19184376
TI  - Behavioral health consultation and primary care: lessons learned.
AB  - This article provides an overview of 20 years of professional experiences with
      developing and implementing a model for integrating behavioral health services
      into primary care. The Primary Care Behavioral Health (PCBH) model is designed to
      provide immediate access to behavioral care for a large number of primary care
      patients by positioning a behavioral health consultant in the exam room area to
      function as a core member of the primary care team. In an initial era of
      discovery, the authors were directly involved in developing and testing a variety
      of new approaches to providing behavioral health services in general medicine. In
      a second era focused on feasibility, the authors worked with Kaiser Permanente,
      the United States Air Force and Navy, the Veteran's Administration, and the
      Bureau of Primary Care to system test this innovative model of integrated care.
      Now in an era devoted to dissemination, the authors review the various roles
      formal research, system level quality improvement initiatives and stakeholder
      analysis play in promoting integrated care. The authors also describe current
      efforts to (1) create a tool that helps systems develop integration targets and
      (2) use the PCBH model as a platform for teaching medical residents and
      behavioral health providers to work together in a redesigned primary care team
      model.

PMID- 19184377
TI  - Optical properties of metacycline, oxytetracycline and chlortetracycline europium
      complexes in the presence of hydrogen peroxide.
AB  - Tetracycline possesses a great tendency to form complexes with a number of
      chemical species, particularly with Eu3+ ions. In this work we investigate the
      europium optical properties of three tetracyclines europium complexes:
      Metacycline (MTc), Oxytetracycline (OTc), and Chlortetracycline (CTc), in the
      presence and absence of hydrogen peroxide (HP). The results show that the
      emission band of EuOTc have enhancement in the presence of hydrogen peroxide. A
      calibration curve was shown for this complex with the best molar ratio obtained.

PMID- 19184378
TI  - Photofunctional polyurethane nanofabrics doped by zinc tetraphenylporphyrin and
      zinc phthalocyanine photosensitizers.
AB  - Polymeric polyurethane nanofabrics doped by zinc tetraphenylporphyrin (ZnTPP)
      and/or zinc phthalocyanine (ZnPc) photosensitizers were prepared by the
      electrospinning method and characterized by microscopic methods, steady-state and
      time-resolved fluorescence, and absorption spectroscopy. Nanofabrics doped by
      both ZnTPP and ZnPc efficiently harvest visible light to generate triplet states
      and singlet oxygen O2(1Delta(g)) with a lifetime of about 15 micros in air
      atmosphere. The energy transfer between the excited singlet states of ZnTPP and
      ground states of ZnPc is described in details. All nanofabrics have bactericidal
      surfaces and photooxidize inorganic and organic substrates. ZnTPP and ZnPc in the
      polyurethane nanofabrics are less photostable than incorporated free-base
      tetraphenylporphyrin (TPP).

PMID- 19184379
TI  - Rotational diffusion of coumarins in aqueous DMSO.
AB  - The rotational dynamics of four structurally similar polar molecules viz.,
      coumarin 440, coumarin 450, coumarin 466 and coumarin 151 has been studied in
      binary mixtures comprising of dimethyl sulphoxide and water at room temperature
      using the steady state fluorescence depolarization method and time correlated
      single photon counting technique. The binary mixtures are characterized by the
      fact that at a particular composition the viscosity (eta) of the solution reaches
      a maximum value that is higher than the viscosities of either of the two co
      solvents. The dielectric properties of the solution change across the composition
      range and the qualitative features of the solvent relaxation dynamics in complex
      systems are known to differ from those in simple solutions. A hook type profile
      of rotational reorientation time (tau(r)) vs viscosity (eta) is obtained for all
      the solutes in dipolar aprotic mixture of dimethyl sulphoxide-water, with the
      rotational reorientation times being longer in organic solvent-rich zone,
      compared to the corresponding isoviscous point in water-rich zone due to strong
      hydrogen bonding. Fluorescence lifetimes as well as rotational reorientation
      times are sensitive to the composition of the binary solvent system under study
      than to the viscosity suggesting the importance of local structure. The results
      are discussed in the light of hydrodynamic and dielectric friction models.

PMID- 19184380
TI  - Simple and sensitive spectrofluorimetric method for the determination of
      oseltamivir phosphate in capsules through derivatization with fluorescamine.
AB  - A new, simple and sensitive spectrofluorimetric method has been developed for the
      determination of oseltamivir phosphate (OSP) in capsules. The method is based on
      the reaction between oseltamivir and fluorescamine in borate buffer solution of
      pH 8.50 to give highly fluorescent derivatives that are measured at 483 nm using
      an excitation wavelength of 381. The different experimental parameters effecting
      the development and stability of the reaction product were carefully studied and
      optimized. The fluorescence intensity concentration plot is rectilinear over the
      range 50-450 ng mL(-1) with a lower detection limit (LOD) of 1.219 ng mL(-1) and
      limit of quantitation (LOQ) of 4.064 ng mL(-1). Selectivity was validated by
      subjecting stock solution of OSP to acidic, basic, oxidative, and thermal
      degradation. No interference was observed from excipients present in
      formulations. The developed method was successfully applied to determination of
      the drug in capsules. The mean % recovery (n = 6) was 100.08. The results
      obtained were in good agreement with those obtained using a reported
      spectrophotometric method.

PMID- 19184381
TI  - Clinical characteristics and outcomes of primary immunodeficiencies in Thai
      children: an 18-year experience from a tertiary care center.
AB  - INTRODUCTION: Early diagnosis and treatment are keys to improve survival of
      patients with primary immunodeficiency diseases (PID). The clinical
      characteristics of these patients in Thailand were not well defined. OBJECTIVE:
      This study aimed to determine the clinical characteristics and outcomes of
      patients with PID in Thailand. METHODS: Medical records of PID patients in the
      past 18 years were reviewed. RESULTS: Sixty-seven children were registered.
      Antibody deficiencies were the most common PID (52.2%), followed by combined T
      cell and B cell immunodeficiencies (25.4%), other well-defined immunodeficiency
      syndromes (11.9%), and phagocytic defects (10.4%). The most common presentations
      of antibody deficiencies, combined T cell and B cell immunodeficiencies, and
      phagocytic defects were infection in the upper respiratory tract (74.3%),
      gastrointestinal tract (82.4%), and skin (85.7%), respectively. The highest
      mortality rate (52.9%) was found in severe combined immunodeficiency. CONCLUSION:
      These results provide clinical features of PID in Thailand. Knowing these
      features will lead to prompt diagnosis and appropriate management.

PMID- 19184382
TI  - Efficient production of bioactive recombinant human Flt3 ligand in E. coli.
AB  - Flt3 ligand (FL) is an early-acting hematopoietic cytokine that stimulates the
      proliferation and differentiation of hematopoietic progenitor cells by activating
      its cognate receptor, Flt3. Recently, FL was shown to potently contribute to the
      development and expansion of antigen-presenting dendritic cells and CD34(+)
      natural killer cell progenitors in vivo. Here, we report a comprehensive method
      for the production of bioactive recombinant human FL (rhFL) in E. coli, suitable
      for structural, biophysical and physiological studies. A soluble form of human FL
      capable of binding to the Ftl3 receptor could be overexpressed in the E. coli
      strain Rosetta-gami(DE3) as inclusion bodies. We have established protocols for
      the efficient in vitro refolding and ensuing purification of rhFL to homogeneity
      (>95%), with yields approaching 5 mg of pure rhFL per liter of culture. The
      ability of rhFL to adopt a bioactive conformation was confirmed via a cell
      proliferation assay and the activation of the Flt3 receptor in the human leukemic
      cell line, OCI-AML3.

PMID- 19184384
TI  - Caspase-independent apoptosis in Friend's erythroleukemia cells: role of
      mitochondrial ATP synthesis impairment in relocation of apoptosis-inducing factor
      and endonuclease G.
AB  - Mitochondria have emerged as the central components of both caspase-dependent and
      independent apoptosis signalling pathways through release of different
      apoptogenic proteins. We previously documented that parental and differentiated
      Friend's erythroleukemia cells were induced to apoptosis by oligomycin and
      H(2)O(2) exposure, showing that the energy impairment occurring in both cases as
      a consequence of a severe mitochondrial F(0)F(1)ATPsynthase inactivation was a
      common early feature. Here we provide evidence for AIF and Endo G mitochondrio
      nuclear relocation in both cases, as a component of caspase-independent apoptosis
      pathways. No detectable change in mitochondrial transmembrane potential and no
      variation in mitochondrial levels of Bcl-2 and Bax are observed. These results
      point to the osmotic rupture of the mitochondrial outer membrane as occurring in
      response to cell exposure to the two energy-impairing treatments under conditions
      preserving the mitochondrial inner membrane. A critical role of the mitochondrial
      F(0)F(1)ATP synthase inhibition in this process is also suggested.

PMID- 19184383
TI  - Conformational isomers of denatured and unfolded proteins: methods of production
      and applications.
AB  - Conformational isomers of denatured-unfolded proteins are rich in numbers and
      varied in shapes. They represent an opulent resource of biological molecules that
      have remained unexploited. The major obstacle in utilizing this untapped
      potential is that it is inherently difficult to isolate and characterize pure
      conformational isomers, not only because of the excessive large number, but also
      because of their instability and rapid inter-conversion. Our lab has developed a
      method for trapping selected conformational isomers of denatured proteins that
      are amenable to isolation, characterization and further applications. The method
      has potential usefulness, ranging from the comprehensive structural
      characterization of denatured proteins, to the elucidation of pathways of protein
      unfolding-folding, to the production of unlimited structurally defined non-native
      protein isomers for biomedical applications.

PMID- 19184385
TI  - A comparison of health behaviors of women in centering pregnancy and traditional
      prenatal care.
AB  - OBJECTIVES: Researchers sought to determine the difference in health behaviors
      between women who receive prenatal care via the Centering Pregnancy approach and
      those involved in traditional prenatal care. METHODS: Using a cross-sectional
      design, adult pregnant women (n = 125) were surveyed from at least 28 weeks
      gestation to delivery. The sample was comprised of primarily white low income
      women. RESULTS: Using multiple linear regression it was determined that women in
      Centering Pregnancy had significantly lower index health behavior scores compared
      with the traditional care group showing that those in Centering Pregnancy
      reported engaging in fewer health promoting behaviors. Furthermore, no
      differences were observed for smoking or weight gain behaviors between groups.
      Additionally, those in Centering Pregnancy reported a lower perceived value of
      prenatal care. CONCLUSIONS: The results of this study suggest that Centering
      Pregnancy is not adequately aiding its patients in adopting healthy behaviors
      during pregnancy.

PMID- 19184386
TI  - Effects of maternal stress on low birth weight and preterm birth outcomes across
      neighborhoods of South Carolina, 2000-2003.
AB  - OBJECTIVE: Studies evaluating the effect of maternal stress on preterm birth
      (PTB) or low birth weight (LBW) and variations across neighborhood contexts have
      been inconclusive. The purpose of the study was to examine the relationships
      among neighborhood contexts, prenatal stress, and birth outcomes, and to further
      explore the modifying effects of neighborhood contexts. METHODS: We evaluated
      this objective by using South Carolina Pregnancy Risk Assessment and Monitoring
      System (PRAMS), 2000-2003 data linked to the 2000 U.S. census data for 8064 women
      (N = 8064). Principal component analysis with varimax rotation was used to group
      stress constructs into four main domains (Financial, Emotional, Traumatic, and
      Spousal-related). We used multilevel logistic regression analysis to estimate the
      adjusted odds ratio for different models. RESULTS: Maternal stress was
      significantly associated with increased risks of low birth weight and preterm
      deliveries. Neighborhood high poverty and low education (upper quartiles) were
      independently associated with low birth weight but not preterm deliveries and
      stress appeared as a partial mediator of contextual effects on birth outcomes.
      The interaction models showed that the relationship between stress and LBW or PTB
      was modified by neighborhood contexts with risks being greater for infants born
      in disadvantaged neighborhoods. CONCLUSIONS: Effects of maternal stress on LBW
      and PTB outcomes may be different for mothers living in different neighborhood
      contexts. Therefore, investigations that fail to examine places of residence
      would most likely not identify mothers at risk of LBW or PTB. Policies to improve
      birth outcomes need to target both places of residence and specific mediating or
      moderating factors associated with deprived neighborhoods of residence.

PMID- 19184387
TI  - Distal balloon occlusion allows epicardial lead placement in a tortuous branch of
      the great cardiac vein.
AB  - Cardiac resynchronization therapy (CRT) is a well established treatment modality
      in heart failure. Using standard techniques, placement of the left ventricular
      (LV) lead is usually successful; however LV lead placement failure remains a
      clinical problem. In the present report, the standard over-the-wire technique was
      not successful due to absence of the necessary support to place the lead into a
      tortuous vein. This was achieved using balloon occlusion of the great cardiac
      vein distal to the target vessel. An 81 year old female candidate for CRT
      presented for biventricular pacemaker implantation. After placement of the right
      ventricular lead, the CS was cannulated and an occlusive venogram was performed.
      A lateral branch was selected as the target vessel. Initial attempts at
      cannulating the vessel were unsuccessful due to the guidewire and telescoping
      delivery system prolapsing into the great cardiac vein. The acute angle prevented
      instrumentation of the branch with the tools available. A second parallel CS
      sheath was advanced to drive a balloon catheter used to occlude the great cardiac
      vein distal to the target vessel. This provided support for the guidewire and
      lead allowing their advancement through the tortuous vessel. Consecutive traction
      on the balloon during also helped to reflect the lead towards the vessel. The
      lead remained stable in its final position on the lateral wall of the LV with
      appropriate thresholds and no diaphragmatic stimulation. We report a case where
      balloon occlusion of the great cardiac vein distal to the target branch aided in
      advancing the LV lead into the desired position. This approach can be used in
      navigating lead placement to branches thought to be unreachable. Techniques such
      as this can decrease the failure rate of CRT implants.

PMID- 19184388
TI  - Agreement of Swiss-adapted international and European guidelines for the
      assessment of global vascular risk and for lipid lowering interventions.
AB  - BACKGROUND: The Swiss national guidelines for the prevention of cardiovascular
      events have been published in 2005 by the Swiss Society of Cardiology (SGK) and
      the working group on lipids and atherosclerosis (AGLA). An agreement for global
      cardiovascular risk assessment and indications for cholesterol lowering among the
      international (IAS-AGLA) and the European (ESC score) guidelines is unknown.
      MATERIAL AND METHODS: Subjects aged >or=45 years were recruited using newspaper
      announcements for the participation in our free of charge cardiovascular
      prevention program of the Vascular Risk Foundation (Varifo). The data served to
      calculate cardiovascular 10 year risk and to compare IAS-AGLA und ESC score with
      respect to risk and lipid lowering indications. RESULTS: The primary prevention
      group included 713 subjects aged 55 +/- 6 years of which 47% were women. The mean
      10-year risk +/- standard deviation was low (IAS-AGLA: 3.9% +/- 4.4% for
      myocardial infarction; ESC score: 1.7% +/- 1.8% for cardiovascular death). In
      those subjects qualifying for a lipid lowering intervention, according to the IAS
      AGLA score or the ESC score, the percentage of agreement between both scores was
      only 18% (kappa value 0.31 [95%CI: 0.22-0.39], p < 0.0001). CONCLUSIONS: Our
      study shows, that the agreement for the available Swiss guidelines (IAS-AGLA, ESC
      score) for initiation of a lipid lowering therapy is low in our primary
      prevention group of subjects aged 45-65 years. According to the PROCAM study,
      about 30% of myocardial infarctions occur in persons with an intermediate risk.
      Therefore an improved risk stratification strategy is necessary.

PMID- 19184389
TI  - Introduction to special issue of Journal of Cross Cultural Gerontology on aging
      and the Middle East.

PMID- 19184390
TI  - Predictors of adherence to diabetes medications: the role of disease and
      medication beliefs.
AB  - Despite the effectiveness of drug therapy in diabetes management high rates of
      poor adherence persist. The purpose of this study was to identify potentially
      modifiable patient disease and medication beliefs associated with poor medication
      adherence among people with diabetes. A cohort of patients with diabetes was
      recruited from an urban primary-care clinic in New York City. Patients were
      interviewed in English or Spanish about: disease beliefs, medication beliefs,
      regimen complexity, diabetes knowledge, depression, self-efficacy, and medication
      adherence (Morisky scale). Logistic regression was used to identify multivariate
      predictors of poor medication adherence (Morisky > 1). Patients (n = 151) had
      diabetes for an average of 13 years with a mean HgA1C of 7.6 (SD 1.7). One-in
      four (28%) were poor adherers to their diabetes medicines. In multivariate
      analyses, predictors of poor medication adherence were: believing you have
      diabetes only when your sugar is high (OR = 7.4;2-27.2), saying there was no need
      to take medicine when the glucose was normal (OR = 3.5;0.9-13.7), worrying about
      side-effects of diabetes medicines (OR = 3.3;1.3-8.7), lack of self-confidence in
      controlling diabetes (OR = 2.8;1.1-7.1), and feeling medicines are hard to take
      (OR = 14.0;4.4-44.6). Disease and medication beliefs inconsistent with a chronic
      disease model of diabetes were significant predictors of poor medication
      adherence. These suboptimal beliefs are potentially modifiable and are logical
      targets for educational interventions to improve diabetes self-management.

PMID- 19184391
TI  - Use of the social competence interview and the anger transcendence challenge in
      individuals with alcohol use disorder.
AB  - Interpersonal stress is a significant determinant of relapse following treatment
      for Alcohol Use Disorders (AUDs), but there remains little specific information
      about the mechanisms underlying the relationship between interpersonal stress and
      AUD relapse. Application of Social Action Theory provides one new approach to
      advancing knowledge about the interpersonal stress-relapse relationship.
      Especially relevant are the Social Action Theory construct of social-emotional
      competence, with its accompanying measurement procedures of the Social Competence
      Interview and the Anger Transcendence Challenge. This study evaluated the use of
      the Social Competence Interview and Anger Transcendence Challenge in a sample of
      63 men and women in AUD intensive outpatient treatment. The results support the
      use of the Social Competence Interview and the Anger Transcendence Challenge with
      an adult AUD clinical sample, so that these measures may help to advance
      knowledge about the relationship between interpersonal stress and alcohol
      relapse.

PMID- 19184394
TI  - HIV partner notification: predictors of discussion and agreements from provider
      reports.
AB  - This study examines organizational, provider, client, and test-event level
      predictors of HIV partner notification (PN) discussion and agreements based on
      providers' most recent HIV-positive post-test counseling session. Staff (n = 621)
      were sampled from for-profit, nonprofit, and county government HIV testing
      organizations (N = 159) in Los Angeles County from 2003 to 2007. Among providers
      who conducted an HIV-positive post-test counseling session (n = 204), 65%
      discussed PN but only 10% had confirmed agreement to provider-involved PN (PIPN).
      In multi-level regression analyses PN discussion was predicted by provider HIV
      test training and knowledge, and patients requesting a test while presenting
      HIV/AIDS symptoms. The strongest predictor of PIPN agreement was public health
      HIV testing settings followed by counseling by program managers or infectious
      disease specialists across settings. None of the injecting drug users or patients
      presenting with AIDS, but not requesting a test, agreed to PIPN. Organizational
      and provider-level interventions on PN will be needed to realize cost-effective
      benefits of expanded HIV testing and counseling.

PMID- 19184392
TI  - Childhood trauma and adulthood physical health in Mexico.
AB  - BACKGROUND: The present study examined the effect of childhood trauma on
      adulthood physical health among a randomly selected sample of adults (N = 2,177)
      in urban Mexico. METHODS: Adults were interviewed about their experiences of
      trauma, post-traumatic stress disorder, depression, and physical health symptoms
      using Module K of the Composite International Diagnostic Interview, the Center
      for Epidemiologic Studies Depression Scale, and the Physical Symptoms Checklist.
      RESULTS: Trauma was prevalent, with 35% reporting a traumatic event in childhood.
      In general, men reported more childhood trauma than women, with the exception of
      childhood sexual violence where women reported more exposure. For men, childhood
      sexual violence was related to total and all physical health symptom subscales.
      For women, childhood sexual violence was related to total, muscular-skeletal, and
      gastrointestinal-urinary symptoms; hazards/accidents in childhood were related to
      total, muscular-skeletal, cardio-pulmonary, and nose-throat symptom subscales.
      Depression mediated the relationship between childhood sexual violence and
      physical health symptoms for men and women. Among women only, PTSD mediated the
      relationship between childhood sexual violence and total, muscular-skeletal, and
      gastrointestinal-urinary symptoms. PTSD also mediated the relationship between
      hazards/accidents in childhood and total, muscular-skeletal, cardio-pulmonary,
      and nose-throat symptoms. CONCLUSION: These findings can be used to increase
      awareness among general practitioners, as well as community stakeholders, about
      the prevalence of childhood trauma in Mexican communities and its impact on
      subsequent physical health outcomes. With this awareness, screening practices
      could be developed to identify those with trauma histories in order to increase
      positive health outcomes among trauma survivors.

PMID- 19184395
TI  - Cytogenetic abnormalities in 179 cases with male infertility in Western Region of
      Turkey: report and review.
AB  - PURPOSE: In this study we aimed to evaluate the postnatally screened karyotype
      results in couples who were referred because of primary infertility between 2000
      and 2006 in Izmir. METHODS: The records of a total of 179 cases were evaluated
      retrospectively. RESULTS: A total of 21 cases (11.74%) showed chromosomal
      alteration. Thirteen (7.26%) were 47,XXY; three (1.68%) were pericentric
      inversion of chromosome 9; one (0.56%) 46,XY/45,XO; one (0.56%)
      46,XY/47,XXY/48,XXXY; one (0.56%) 46,XY,t(X;1); one (0.56%)
      46,XY/46,XY,del(Y)(q11.2) and one (0.56%) 46,XX. CONCLUSIONS: The rate of
      gonosomal chromosomal abnormalities was nearly three times higher in our region
      than the rate in the literature. Chromosomal analysis is strongly suggested
      particularly in those who suffer fertility problems.

PMID- 19184396
TI  - Preconceptional diagnosis for Robertsonian translocation as an alternative to
      preimplantation genetic diagnosis in two situations: a pilot study.
AB  - INTRODUCTION: Preimplantation genetic diagnosis (PGD) is widely used for women
      heterozygous for a Robertsonian translocation. Preconceptional diagnosis (PCD),
      performed before fertilization, may be an alternative to PGD, especially in
      countries where PGD is restricted or prohibited, as in France. It could also give
      different information and clarify the influence of reproductive and obstetric
      history. METHODS: In our study, translocation was diagnosed before ICSI in five
      cases (group A), and after newborn or fetal aneuploidy or miscarriage in two
      cases, (group B). RESULTS: First polar body (PB1) analysis using acrocentric
      centromeric probes was done for 85 PB1s, and aneuploidy rate was at 42.4%. Oocyte
      aneuploidy rate differed (p<0.0001) between groups A and B (30% vs 84%). Despite
      the small group sizes, we demonstrate a correlation (p=0.0358) of aneuploidy rate
      in polar bodies after 2 or more attempts. Three live births were recorded, all in
      group A. DISCUSSION: PCD could thus be an alternative to PGD. This pilot study
      also provides new prognostic information taking into account the women's natural
      history, but further confirmation is required.

PMID- 19184397
TI  - Optimization of IVF pregnancy outcomes with donor spermatozoa.
AB  - PURPOSE: To identify risk factors for suboptimal IVF outcomes using insemination
      with donor spermatozoa and to define a lower threshold that may signal a
      conversion to fertilization by ICSI rather than insemination. METHOD:
      Retrospective, age-matched, case-control study of women undergoing non-donor
      oocyte IVF cycles using either freshly ejaculated (N=138) or cryopreserved donor
      spermatozoa (N=69). Associations between method of fertilization, semen sample
      parameters, and pregnancy rates were analyzed. RESULTS: In vitro fertilization of
      oocytes with donor spermatozoa by insemination results in equivalent
      fertilization and pregnancy rates compared to those of freshly ejaculated
      spermatozoa from men with normal semen analyses when the post-processing motility
      is greater than or equal to 88%. IVF by insemination with donor spermatozoa when
      the post-processing motility is less than 88% is associated with a 5-fold
      reduction in pregnancy rates when compared to those of donor spermatozoa above
      this motility threshold. When the post-processing donor spermatozoa motility is
      low, fertilization by ICSI is associated with significantly higher pregnancy
      rates compared to those of insemination. CONCLUSION: While ICSI does not need to
      be categorically instituted when using donor spermatozoa in IVF, patients should
      be counseled that conversion from insemination to ICSI may be recommended based
      on low post-processing motility.

PMID- 19184398
TI  - Effect of embryonic fibroblast cell co-culture on development of mouse embryos
      following exposure to visible light.
AB  - PURPOSE: To determine the effects of visible light on development of mouse
      embryos and the potential of fibroblast cells to overcome deleterious effects of
      visible light on mouse preimplantation stage embryos. METHODS: Two-cell mouse
      embryos were randomly allocated to un-exposed group (control) and exposed group
      receiving 1600 lx visible light for various time lengths. Both exposed and un
      exposed embryos were co-cultured with either Mouse Embryonic Fibroblast (MEF) or
      Human Embryonic Fibroblast (HEF). Developmental rate of embryos at day 3
      (morula), 4 (expanded blastocyst) and 5 (hatching or hatched blastocyst) was
      evaluated. RESULTS: Exposure of embryos to visible light for 30 min decreased
      developmental rate significantly (P<0.01). Developmental rate of exposed embryos
      co-cultured with MEF (58%; p<0.05 both at day 4 and 5) and HEF (67%; P<0.01 both
      at day 4 and 5) was higher than control. CONCLUSIONS: Visible light adversely
      affects embryo development in a time-dependent manner. Feeder cells may enhance
      embryo development particularly when suboptimal conditions are involved.

PMID- 19184399
TI  - Effect of leukocytospermia and processing by discontinuous density gradient on
      sperm nuclear DNA fragmentation and mitochondrial activity.
AB  - PURPOSE: To assess the effect of leukocytospermia and semen processing on sperm
      DNA and mitochondria. METHODS: Twenty-two patients with and 41 without
      leukocytospermia were included. Sperm DNA fragmentation was assessed by the Comet
      assay, and mitochondrial activity by a colorimetric method for active
      mitochondria. Semen was processed using Percoll, and motility, DNA fragmentation,
      and mitochondrial activity were analyzed pre- and post-processing. RESULTS: No
      differences were observed in age, abstinence, volume, sperm morphology,
      progressive motility, concentration, and vitality (p>0.10). Variables were
      grouped according to time (pre- vs post-processing) and group (leukocytospermia
      vs non-leukocytospermia) because no interactions could be observed.
      Leukocytospermia was associated to increased DNA fragmentation, while semen
      processing led to a decrease in DNA fragmentation and to increased mitochondrial
      activity. CONCLUSION: While semen processing selects sperm with higher rates of
      DNA integrity independent of the presence or absence of leukocytes in semen,
      samples without leukocytospermia present more sperm without DNA fragmentation.
      Semen processing also selects sperm with higher mitochondrial activity.

PMID- 19184400
TI  - Can executive functions explain the relationship between Attention Deficit
      Hyperactivity Disorder and social adjustment?
AB  - This study examined the ability of executive functions (EF) to account for the
      relationship between Attention Deficit Hyperactivity Disorder (ADHD) status and
      social adjustment as indexed by parent and teacher report and by performance on a
      standardized observational "chat room" task. Children with the Combined subtype
      (ADHD-C; n = 23), the Primarily Inattentive Subtype (ADHD-I; n = 33), and non
      ADHD controls (n = 36) participated. EF did not mediate the relationship between
      ADHD status and parent or teacher report of social adjustment. EF accounted for
      about 40-50% of the variance between ADHD status and the ability of children to
      detect subtle verbal cues as well as memory for the conversation in the chat room
      task, but did not mediate the relationship between ADHD and the number of
      prosocial, hostile, or on-topic statements that were made. Results are consistent
      with other recent reports, and suggest that the role of EF deficits in the
      production of social skill deficits in ADHD may not be as prominent as is
      typically assumed. The implications for the development of intervention programs
      designed to target core cognitive etiologic factors are discussed.

PMID- 19184401
TI  - Equanimity to excess: inhibiting the expression of negative emotion is associated
      with depression symptoms in girls.
AB  - Emotion dysregulation is often invoked as an important construct for
      understanding risk for psychopathology, but specificity of domains of emotion
      regulation in clinically relevant research is often lacking. In the present study
      Gross' (2001) model of emotion regulation is used to generate hypotheses
      regarding the relative contribution of two specific types of deficits in emotion
      regulation, inhibited and disinhibited expression of negative emotion, to
      individual differences in depressive symptoms in preadolescent girls. A sample of
      232 9-year-old girls was recruited from a community based study. Depression
      symptoms were assessed via diagnostic interview. The mother and interviewer rated
      the girl's level of impairment. Questionnaires and observations were used to
      assess inhibited and disinhibited expression of negative emotion. Differences in
      inhibited expression of negative emotion typically explained more variance in
      depressive symptoms and impairment across informants than did disinhibited
      expression of negative emotion. Although disinhibited expression of negative
      emotion is associated with depression and impairment, inhibited expression
      appeared to be a necessary ingredient, suggesting that inhibited expression may
      be a particularly relevant deficit in emotion regulation in the development of
      depression in females.

PMID- 19184402
TI  - Mediational pathways through which positive and negative emotionality contribute
      to anhedonic symptoms of depression: a prospective study of adolescents.
AB  - This study takes a developmental psychopathological approach to examine
      mechanisms through which baseline levels of positive emotionality (PE) and
      negative emotionality (NE) prospectively predict increases in anhedonic
      depressive symptoms in a community sample of 350 adolescents (6th-10th graders).
      Dependent stressors mediated the relationship between baseline levels of NE and
      anhedonic depressive symptoms after controlling for initial symptoms. Supportive
      relationships mediated the relationship between baseline levels of PE and
      anhedonic depressive symptoms, after controlling for baseline symptoms. In
      addition, NE X PE interacted to predict later anhedonic depressive symptoms, such
      that adolescents with low levels of PE and high levels of NE experienced the
      greatest increase in anhedonic depressive symptoms. Last, supportive
      relationships interacted with baseline PE to predict prospective changes in
      anhedonic depressive symptoms, such that adolescents with low PE and low
      supportive relationships experienced the greatest increase in anhedonic
      depressive symptoms. Results are discussed in terms of current theoretical models
      of the link between temperament and depression.

PMID- 19184403
TI  - Predicting growth curves of early childhood externalizing problems: differential
      susceptibility of children with difficult temperament.
AB  - Using an accelerated longitudinal design, the development of externalizing
      problems from age 2 to 5 years was investigated in relation to maternal
      psychopathology, maternal parenting, gender, child temperament, and the presence
      of siblings. The sample consisted of 150 children selected at age 2-3 years for
      having high levels of externalizing problems. Parenting was measured using
      observational methods, and maternal reports were used for the other variables.
      Overall, mean levels of externalizing problems decreased over time, and higher
      initial levels (intercept) were related to a stronger decrease (negative slope)
      in externalizing problems. Results showed that higher levels of maternal
      psychopathology were related to less decrease in early childhood externalizing
      problems. Parental sensitive behavior predicted a stronger decrease in
      externalizing problems, but only for children with difficult temperaments. A
      stronger decrease of externalizing problems in children with older siblings also
      pertained only to children with difficult temperaments. Thus, temperamentally
      difficult children appear to be more susceptible to environmental influences on
      the development of externalizing behaviors. Our results indicate that the role of
      siblings in early childhood externalizing problems deserves more research
      attention, and that intervention efforts need to take into account temperamental
      differences in children's susceptibility to environmental influences.

PMID- 19184404
TI  - Melanocortin-4 receptor gene polymorphisms in obese patients.
AB  - Obesity is a complex disease caused by both genetics and environmental factors.
      Melanocortin-4 receptor (MC4R) (MIM 155541) gene polymorphisms were reported to
      be the cause of monogenic obesity in humans. We studied three polymorphisms
      (Val50Met, Val103Ile, and Ser58Cys) and a mutation (Asn274Ser) of the MC4R gene
      in 203 obese patients and in 110 healthy subjects in the Turkish population. A
      high incidence of Val103Ile and Val50Met polymorphisms as well as the Asn274Ser
      mutation was found in the obese patients, whereas no significant correlation was
      found regarding the Ser58Cys polymorphism. We conclude that there is a
      concordance between the polymorphisms (Val103Ile, Val50Met, Ser58Cys) that were
      first studied in the Turkish population with obesity.

PMID- 19184405
TI  - Genetic diversity and variation among botanical varieties of old Portuguese wheat
      cultivars revealed by ISSR assays.
AB  - Inter-simple sequence repeats (ISSRs) were used for genetic diversity analyses of
      an Old Portuguese wheat collection. Eighteen primers produced 96.3 and 98.5% of
      ISSR polymorphism in bread and durum wheat cultivars, respectively. The
      unweighted pair group method with arithmetical averages (UPGMA) phenogram clearly
      split all cultivars based on their species/ploidy, reflecting a defined genetic
      structure. ISSRs revealed high genetic diversity at interspecific, intraspecific,
      and intercultivar levels. Thirty-three exclusive ISSR markers were found.
      Cultivars were clustered according to their botanical varieties and, in a few
      cases, with their homonym(s). No statistically significant differences were found
      between genetic diversity parameters of durum and bread wheat, probably due to
      high intraspecific diversity. Similar analyses were performed among botanical
      varieties, and their relationships were defined. Cladograms resembled UPGMA
      clustering. This highly genetically diverse Old wheat collection will be
      conserved and maintained, and it could be further used in breeding programs to
      widen the narrow genetic basis of modern wheat varieties and to avoid the loss of
      rare and unique alleles.

PMID- 19184406
TI  - Evaluation of genetic variation in the clown Knifefish, Chitala chitala, using
      allozymes, RAPD, and microsatellites.
AB  - Twenty-seven enzyme systems, six random amplified polymorphic DNA (RAPD) primers,
      and two microsatellite loci were tested to determine intraspecific divergence in
      the natural population of the endangered Indian featherback fish, Chitala
      chitala, for the first time. The 262 samples of C. chitala were collected from
      six riverine locations in India: the Satluj, Ganga (Ghagra, Bhagirathi, and
      Brahmaputra), Mahanadi, and Narmada river systems. The analysis revealed
      population subdivisions, with an F(ST) value from 0.1235 (95% confidence 0.0868
      0.1621) for RAPD and a combined F(ST) of 0.0344 (95% confidence 0.0340-0.0350)
      for microsatellite loci. An analysis of 38 allozyme loci did not reveal any
      polymorphism in the samples from any of the riverine localities; a possible
      explanation for this could be that the ancestors of Chitala could have faced a
      population reduction in prehistoric periods, as low allozyme variation is also
      reported for other species of Chitala from south Asia.

PMID- 19184407
TI  - Cloning and characterization of the SSB-1 and SSB-4 genes expressed in zebrafish
      gonads.
AB  - The protein of the gustavus (gus) gene has a typical SOCS box domain and repeats
      in the splA and RyR (SPRY) domains. GUS can interact with Vasa and is necessary
      for the specification of germ cells. We cloned two zebrafish genes, SSB-1 and SSB
      4 (SPRY domain SOCS box proteins). Phylogenetic analysis shows that zebrafish SSB
      1 and SSB-4 are clustered into clades of SSB-1-like and SSB-4-like genes from
      other species. RT-PCR analysis of tissues revealed that zebrafish SSB-1 and -4
      are expressed in the ovary and testis. We investigated the spatial expression
      patterns of zebrafish SSB-1 and -4 in embryos from the two-cell stage to 72 h
      postfertilization (hpf) using whole-mount in situ hybridization. SSB-1 and -4
      transcripts were present in all blastomeres during the early embryonic stages,
      but the genes differ in their expression pattern. SSB-4 mRNA was located in the
      region of the primordial germ cells in 24 and 72 hpf embryos, but SSB-1 mRNA was
      not detected at these stages. We hypothesize that SSB-4 plays a role in the early
      development of germ cells.

PMID- 19184409
TI  - Is it necessary to discuss person-oriented research in community psychology?
AB  - A brief overview of the person orientation is provided. It is then argued that
      research in community psychology, similar to every other field in psychology, has
      mainly focused on variables, not individuals. Suggestions are provided for how
      the person orientation can be applied to understanding settings and environments
      as well as the theoretical and methodological contributions community
      psychologists can make to further person oriented methods.

PMID- 19184408
TI  - Mitochondrial DNA sequence variation of the swallowtail butterfly, Papilio
      xuthus, and the cabbage butterfly, Pieris rapae.
AB  - We analyzed a portion of mitochondrial COI gene sequences (658 bp) to investigate
      the genetic diversity and geographic variation of the swallowtail butterfly,
      Papilio xuthus L. (Lepidoptera: Papilionidae), and the cabbage butterfly, Pieris
      rapae L. (Lepidoptera: Pieridae). Papilio xuthus showed a moderate level of
      sequence divergence (0.91% at maximum) in 15 haplotypes, whereas Pi. rapae showed
      a moderate to high level of sequence divergence (1.67% at maximum) in 30
      haplotypes, compared with other relevant studies. Analyses of population genetic
      structure showed that most populations are not genetically differentiated in both
      species. The distribution pattern of both species appears to be consistent with
      category IV of the phylogeographic pattern sensu Avise: a phylogenetic
      continuity, an absence of regional isolation of mtDNA clones, and extensive
      distribution of close clones. The observed pattern of genetic diversity and
      geographic variation of the two butterfly species seem to reflect the abundant
      habitats, abundant host plants, and flying abilities in connection with the lack
      of historical biogeographic barriers.

PMID- 19184410
TI  - Public policy, participation and the third position: the implication of engaging
      communities on their own terms.
AB  - Policy development and implementation should be fundamental for community
      psychologists in their endeavors to create social change. Policy necessarily is
      engaged at broad social and political levels, but it is mediated through
      communities and individuals, and thus appealing for our discipline. We argue that
      there are increasing opportunities for social input in liberal democracies with
      the growing awareness of the need to consider social factors in policy. Public
      participation is one aspect of policy development, but it can be problematic and
      can disempowered communities, especially disadvantaged communities. Using the
      framework of the 'third position', a case study of attempts to ameliorate
      institutional oppression of Australian Aboriginal people through policy change is
      described. Structural reform to community engagement is described in terms of
      empowerment and capacity building. Power relationships are deconstructed to allow
      understandings of the dynamics of policy change, and the broader implications for
      community psychological praxis are discussed.

PMID- 19184411
TI  - Four keys to success (theory, implementation, evaluation, and resource/system
      support): high hopes and challenges in participation.
AB  - In this article, I attempt to merge two themes. First, there is often a large gap
      between high hopes about impacts of policies or programs and the demonstrated
      results. I describe four keys/threats to success in any social problem area:
      theory, implementation, evaluation, and resource/system support. Second, I
      present theory and research from over 30 years of work on participation,
      conducted by my colleagues and myself that can illuminate and be illuminated by
      theory, implementation, evaluation, and resource/system support. I offer ideas
      for solutions that increase the probability of success. I conclude with the need
      to have high hopes tempered by theory and research to develop realistically
      ambitious solutions to social problems.

PMID- 19184412
TI  - Protective role of lithium in ameliorating the aluminium-induced oxidative stress
      and histological changes in rat brain.
AB  - This study was carried out to investigate the effects of lithium (Li)
      supplementation on aluminium (Al) induced changes in antioxidant defence system
      and histoarchitecture of cerebrum and cerebellum in rats. Al was administered in
      the form of aluminium chloride (100 mg/kg b.wt./day, orally) and Li was given in
      the form of Li carbonate through diet (1.1 g/kg diet, daily) for a period of 2
      months. Al treatment significantly enhanced the levels of lipid peroxidation and
      reactive oxygen species in both the cerebrum and cerebellum, which however were
      decreased following Li supplementation. The enzyme activities of catalase,
      superoxide dismutase (SOD) and glutathione reductase (GR) were significantly
      increased in both the regions following Al treatment. Li administration to Al-fed
      rats decreased the SOD, catalase and GR enzyme activities in both the regions;
      however, in cerebellum the enzyme activities were decreased in comparison to
      normal controls also. Further, the specific activity of glutathione-s-transferase
      and the levels of total and oxidized glutathione were significantly decreased in
      cerebrum and cerebellum following Al treatment, which however showed elevation
      upon Li supplementation. The levels of reduced glutathione were significantly
      decreased in cerebrum but increased in cerebellum following Al treatment, which
      however were normalized upon Li supplementation but in cerebellum only. Apart
      from the biochemical changes, disorganization in the layers of cerebrum and
      vacuolar spaces were also observed following Al treatment indicating the
      structural damage. Similarly, the loss of purkinje cells was also evident in
      cerebellum. Li supplementation resulted in an appreciable improvement in the
      histoarchitecture of both the regions. Therefore, the study shows that Li has a
      potential to exhibit neuroprotective role in conditions of Al-induced oxidative
      stress and be explored further to be treated as a promising drug against
      neurotoxicity.

PMID- 19184413
TI  - Identifying the "sentinel lymph nodes" for arm drainage as a strategy for
      minimizing the lymphedema risk after breast cancer therapy.

PMID- 19184414
TI  - Complementary and alternative therapy use before and after breast cancer
      diagnosis: the Pathways Study.
AB  - Many women use complementary and alternative medicine (CAM) to maintain or
      improve their health. We describe CAM use among the first 1,000 participants
      enrolled in the Pathways Study, an ongoing prospective cohort study of women
      diagnosed with breast cancer (BC). Participants, identified by rapid case
      ascertainment in Kaiser Permanente Northern California, are women > or = 21 years
      diagnosed with first invasive BC. Comprehensive baseline data are collected on
      CAM use through in-person interviews. Study participants include 70.9% non
      Hispanic whites, 10.2% Hispanics, 9.0% Asians, 6.5% African-Americans, and 3.4%
      others. Most women (82.2%) were diagnosed with AJCC stage I/II BC at average (+/
      SD) age 59.5 (+/-12.0) years and reported prior use of at least one form of CAM
      (96.5% of participants). In the 5 years before diagnosis, CAM therapies used at
      least weekly by >20% of women included green tea, glucosamine, omega-3 fatty
      acids, prayer and religion. CAM use was high (86.1% of participants) in the
      period immediately following diagnosis; 47.5% used botanical supplements, 47.2%
      used other natural products, 28.8% used special diets, 64.2% used mind-body
      healing, and 26.5% used body/energy/other treatments. In multivariable analyses,
      frequent use of each CAM modality before and after diagnosis was associated with
      use of other CAM modalities and other health behaviors (i.e., high
      fruit/vegetable intake, lower BMI). CAM use before and after BC diagnosis is
      common in this diverse group of women. Our results emphasize the need for
      clinicians to discuss CAM use with all BC patients.

PMID- 19184415
TI  - Stimulation of the bradykinin B(1) receptor induces the proliferation of estrogen
      sensitive breast cancer cells and activates the ERK1/2 signaling pathway.
AB  - Kinin peptides exert multiple biological effects by binding to two types of G
      protein-coupled receptors known as B(1) (B(1)R) and B(2) receptors. Expression of
      the B(1)R in human breast cancer was recently reported, but up to now the
      consequences of its stimulation are unknown. Our aims were (1) to investigate the
      capacity of B(1)R to trigger cell proliferation in breast cancer cells, (2) to
      explore some of the downstream events occurring after B(1)R stimulation that may
      be linked to cell proliferation, and (3) to determine whether human breast tumors
      express potentially active B(1)R assessed by the binding of a radiolabeled
      agonist. Breast cancer cells expressed both the mRNA and the immunoreactive
      protein of B(1)R that once stimulated triggered cell proliferation at nanomolar
      concentrations of the ligand. Inhibitor studies suggested that the proliferative
      effects depend on the activity of epidermal growth factor receptor and subsequent
      ERK1/2 mitogen-activated protein kinases phosphorylation. B(1)R binding sites,
      were detected in 3/4 fibroadenomas, in 4/4 ductal carcinomas in situ and in 11/13
      invasive ductal carcinomas. The B(1)R-epidermal growth factor receptor crosstalk
      may be a key interaction that maintains tumor growth, and antagonism of B(1)R may
      be a valuable alternative for the treatment of breast cancer.

PMID- 19184416
TI  - Alcohol intake over the life course and mammographic density.
AB  - Alcohol intake is one of the few modifiable risk factors for breast cancer.
      Current alcohol intake has been associated with mammographic density, a strong
      intermediate marker of breast cancer risk, though few studies have examined the
      effect of both current and average lifetime alcohol intake. We interviewed 262
      participants from a New York birth cohort (born 1959-1963) and obtained
      mammograms from 163 (71.5% of participants with a mammogram). We collected
      information on alcohol intake by beverage type separately for each decade of
      life. We used multivariable linear models to assess the associations between
      current and average lifetime alcohol intake and mammographic density using a
      quantitative measure of density from digitized images. Overall, current alcohol
      intake was more strongly associated with mammographic density than average
      lifetime alcohol intake; compared with nondrinkers, those with current intake of
      seven or more servings per week had on average 12.3% (95% CI: 4.3, 20.4) higher
      density, adjusted for average lifetime alcohol intake, age, and body mass index.
      We observed a consistent inverse association for red wine intake and mammographic
      density, suggesting that the positive association between mammographic density
      and overall alcohol intake was driven by other types of alcoholic beverages. Our
      findings support an association between current alcohol intake and increased
      mammographic density independent of the effect of average lifetime alcohol
      intake. If replicated, our study suggests that reducing current alcohol
      consumption, particularly beer and white wine intake, may be a means of reducing
      mammographic density regardless of intake earlier in life.

PMID- 19184417
TI  - Detection and characterization of a sialoglycosylated bacterial ABC-type
      phosphate transporter protein from patients with visceral leishmaniasis.
AB  - We report the discovery and characterization of a glycosylated bacterial ABC-type
      phosphate transporter isolated from the peripheral blood mononuclear cell (PBMC)
      fraction of patients with visceral leishmaniasis (VL). Three disease-associated 9
      O-acetylated sialoglycoproteins (9-O-AcSGPs) of 19, 56 and 65 kDa, respectively,
      had been identified and their purity, apparent mass and pI established by SDS
      PAGE and isoelectric focusing. Western blot analyses showed that the 9-O
      acetylated sialic acid is linked via alpha2-->6 linkage to a subterminal N
      acetylgalactosamine. For the 56 kDa protein, N- as well as O-glycosylations were
      demonstrated by specific glycosidase treatment and found to account for more than
      9 kDa of the protein mass. The presence of sialic acids was further confirmed
      through thin layer chromatography, fluorimetric HPLC and electrospray ionization
      mass spectrometry. The protein was identified by mass spectrometry and de novo
      sequencing of five tryptic fragments as a periplasmic ABC-type phosphate
      transporter of Pseudomonas aeruginosa. The amino acid sequences of the assigned
      peptides had 83-100% identity with the NCBI entry for a Pseudomonas transporter
      protein. Based on the recently reported X-ray structure of a human phosphate
      binding protein, we predicted a 3D structural model for the 56 kDa protein using
      homology and threading methods. The most probable N- and O-glycosylation sites
      were identified by combinations of sequence motif-searching bioinformatics tools,
      solvent accessibility calculations, structural environment analyses and mass
      spectrometric data. This is the first reported glycosylation as well as
      sialylation of the periplasmic component of an ABC-type phosphate transporter
      protein and of one of few identified bacterial glycoproteins.

PMID- 19184418
TI  - Post-translational and transcriptional regulation of glycolipid
      glycosyltransferase genes in apoptotic breast carcinoma cells: VII. Studied by
      DNA-microarray after treatment with L-PPMP.
AB  - Functions of glycosphingolipids on the eukaryotic cell membranes during the onset
      of oncogenic processes and cell death are not well understood. Inhibitors of
      glycosphingolipid biosynthesis were recently found to trigger apoptosis in many
      carcinoma including breast cancer SKBR-3, MCF-7, and MDA-468 cells through either
      intrinsic or extrinsic apoptotic pathways as we previously reported. These anti
      cancer inhibitors could increase ceramide concentration by blocking functions of
      glycolipid glycosyltransferases (GLTs). In this study, using a novel fluorescent
      dye (ASK-0) revealed the damage of cell organelle membranes by an inhibitor of
      glucosylceramide biosynthesis (L-PPMP). A highly drug- and cell-dependent
      regulation of MAPKs was also found by cis-platin and L-PPMP when inducing
      apoptosis in SKBR-3, MCF-7, and MDA-468 cells. A dose and time-dependent
      regulation of GLTs were investigated by enzymatic assay and DNA microarray
      analyses. These GLTs are involved in biosynthesis of Le(X) and sialosyl-Le(X)
      (neolactosyl-ceramide series) such as GalT-4 (UDP-Gal: LcOse3cer beta
      galactosyltransferase, GalT-5 (UDP-Gal: nLcOse4Cer alpha1,
      3galactosyltransferase, FucT-3 (GDP-Fucose: LM1 alpha1, 4fucosyltransferase). A
      similar effect was observed with the GLTs involved in the biosyntheses of Gg
      series gangliosides, such as SAT-4 (CMP-NeuAc: GgOse4Cer alpha2,
      3sialyltransferase, and SAT-2 (CMP-NeuAc: GM3 alpha2, 8sialyltransferase). The
      glycol-related gene DNA-microarrays also suggested the transcriptional regulation
      of several GLTs involved in the biosynthesis of neolactosylceramide containing
      cell-surface antigens in these apoptotic breast carcinoma cells. In the early
      apoptotic stages (2 to 6 h after L-PPMP treatment) in addition to GlcT-1 gene,
      several genes (betaGalTs and betaGlcNAcTs) in the SA-Le(a) pathway were
      stimulated.

PMID- 19184419
TI  - Toxicity of soybean rust fungicides to freshwater algae and Daphnia magna.
AB  - Soybeans are intensively grown over large swaths of land in the Midwestern US.
      Introduction of the pathogenic fungus responsible for Soybean Rust (Phakopsora
      pachyrhizi) will likely result in a significant increase in the environmental
      load of strobilurin and conazole fungicides. We determined the toxicity of six
      such fungicides to the unicellular algae Pseudokirchneriella subcapitata and the
      aquatic invertebrate, Daphnia magna. We found that levels of concern of some
      fungicides were lower than annual average runoff concentrations predicted for
      Indiana. Our results suggest that pyraclostrobin and propiconazole, and to a
      lesser extent tebuconazole, may cause impacts to algae and daphnids in areas
      where soybeans are intensively grown. More studies are needed to describe the
      ecological effects of sublethal exposures to these fungicides, as well as
      monitoring environmental concentrations in watersheds where these fungicides are
      applied to soybeans.

PMID- 19184420
TI  - Laplace's approximation for relative risk frailty models.
AB  - Relative risk frailty models are used extensively in analyzing clustered and/or
      recurrent time-to-event data. In this paper, Laplace's approximation for
      integrals is applied to marginal distributions of data arising from parametric
      relative risk frailty models. Under regularity conditions, the approximate
      maximum likelihood estimators (MLE) are consistent with a rate of convergence
      that depends on both the number of subjects and number of members per subject. We
      compare the approximate MLE against alternative estimators using limited
      simulation and demonstrate the utility of Laplace's approximation approach by
      analyzing U.S. patient waiting time to deceased kidney transplant data.

PMID- 19184421
TI  - The additive hazards model with high-dimensional regressors.
AB  - This paper considers estimation and prediction in the Aalen additive hazards
      model in the case where the covariate vector is high-dimensional such as gene
      expression measurements. Some form of dimension reduction of the covariate space
      is needed to obtain useful statistical analyses. We study the partial least
      squares regression method. It turns out that it is naturally adapted to this
      setting via the so-called Krylov sequence. The resulting PLS estimator is shown
      to be consistent provided that the number of terms included is taken to be equal
      to the number of relevant components in the regression model. A standard PLS
      algorithm can also be constructed, but it turns out that the resulting predictor
      can only be related to the original covariates via time-dependent coefficients.
      The methods are applied to a breast cancer data set with gene expression
      recordings and to the well known primary biliary cirrhosis clinical data.

PMID- 19184422
TI  - Prevalence of proximal neoplasms among asymptomatic patients according to distal
      colorectal findings.
AB  - Colorectal cancer has been described in association with hyperplastic polyposis.
      Only half of proximal colon cancers are associated with distal adenomas. To
      compare the prevalence of proximal and advanced neoplasia between patients with
      distal hyperplastic polyps only; with distal adenomas with or without
      hyperplastic polyps; and with no distal polyps, we retrospectively analyzed data
      of 1,064 adults who underwent colonoscopy. Of these patients, 3% had neoplasia.
      Proximal neoplasia occurred in 0.8% of 945 patients with no distal polyps,
      compared to none of 19 with distal hyperplastic polyps (P > 0.05) and 6% with
      distal adenomas (P > 0.05). Proximal advanced neoplasia occurred in 0.6% patients
      with no distal polyps, compared with none with distal hyperplastic polyps (P >
      0.05) and 6% with distal adenomas (P > 0.05). In conclusion, patients with distal
      hyperplastic polyps, unlike those with distal adenomas, do not exhibit an
      increased risk for proximal neoplasia or proximal advanced neoplasia compared to
      those with no distal polyps.

PMID- 19184423
TI  - Squamous cell carcinoma in a large epiphrenic esophageal diverticulum.
AB  - Carcinoma is rare in an esophageal diverticulum. The case of a 53-year-old man
      with a large mass in a long-standing symptomatic epiphrenic esophageal
      diverticulum is presented in this study. Squamous cell carcinoma in the
      diverticulum with pleural invasion was diagnosed after surgical diverticulectomy.
      The patient underwent subtotal esophagectomy with locoregional lymph node
      dissection and reconstruction with gastric tube because of micro-invasion at the
      surgical margin. The patient developed malignant pleural effusion at 6 months
      after surgery, and he eventually expired 3 months later. Carcinoma can develop in
      esophageal diverticula and is usually diagnosed at an advanced stage with poor
      prognosis.

PMID- 19184425
TI  - A more than one-hundred-fold higher per capita rate of authorship of five
      democratic nations versus their relatively undemocratic neighboring nations among
      6,437 articles in 14 medical journals: does democracy and civil liberties promote
      intellectual creativity and medical research?
AB  - The aim of this work is to compare medical research productivity between
      democratic countries and their relatively undemocratic neighbors to identify
      mechanisms to promote medical research. Country of authorship was determined
      manually for articles published in 14 medical journals in 2005, and compared
      pairwise for democracies vs. relatively undemocratic nations: Israel vs. the rest
      of the Middle East; Japan vs. Russia; South Korea vs. North Korea; and Taiwan or
      Hong Kong vs. Mainland China. Democracies were quantitatively defined according
      to the Freedom House Index and the Economist's Index of Democracy. The frequency
      of publication of Israeli authors of unsolicited articles (excludes editorials)
      was found to be 1.08%, while its percentage of the world population is only .11%
      (OR = 9.97, 95%-ORCI: 4.30-23.1, P < 0.0001). This increase was invariant for
      more prestigious original articles (investigations) vs. less prestigious review
      articles or case reports, and for more prestigious high-impact factor journals
      vs. less prestigious low-impact factor journals. This increase was apparently not
      due to political favoritism: the relative frequency (RF) of Israeli authors of
      unsolicited articles was significantly higher than the RF of Israeli authors of
      solicited articles (i.e., invited editorials) (1.08% vs. 0.13%, OR = 8.38, 95%
      ORCI = 1.46-48.1, P = 0.007); and was significantly higher than the RF of Israeli
      editorial board members (1.08% vs. 0.08%, OR = 13.0, 95%-ORCI = 2.27-74.7, P <
      0.0001). Contrariwise, the frequency of publication of authors from the Middle
      East excluding Israel was 0.30%, while its percentage of the world population is
      4.04% (OR = 0.071, 95%-ORCI = 0.04-0.12, P < 0.0001). The OR of Israeli
      authorship was incredibly 140.4-fold higher than the OR of the MEEI! The OR of
      authors of other democratic countries was also more than 100-fold the OR of
      authors of their undemocratic neighbors: Japan (OR = 4.93, 95%-ORCI = 3.82-6.36,
      P < 0.0001) vs. Russia (OR = 0.005, 95%-ORCI = 0.00-0.06, P < 0.0001); South
      Korea (OR = 3.48, 95%-ORCI = 2.29-5.31, P < 0.0001) vs. North Korea (OR < 0.36,
      95%-ORCI = 0.00-0.35, P < 0.0001); Taiwan (OR = 5.12, 95%-ORCI = 2.85-9.19, P <
      0.0001) or Hong Kong (OR = 9.21, 95%-ORCI = 3.51-24.2, P < 0.0001) vs. Mainland
      China (OR = 0.028, 95%-ORCI = 0.019-0.041, P < 0.0001). The OR of national
      authorship was closely correlated with two indices of democracy: correlation
      coefficient with Freedom House Index = 0.83, and correlation coefficient with the
      Economist's Democracy Index = 0.76. The OR of national authorship was also
      (mildly less) correlated with per capita income (corr. coeff. = 0.75). In
      conclusion, five democracies exhibit a remarkably higher relative frequency of
      medical publications than their relatively undemocratic neighbors. The relative
      frequency of authorship was, furthermore, extremely strongly correlated with
      democracy and political freedom. The freedom hypothesis may help explain this
      phenomenon: political freedom and liberty in democracies may promote intellectual
      creativity and medical research. This hypothesis should be tested by a
      multivariate analysis of univariate risk factors of medical authorship for all
      nations.

PMID- 19184424
TI  - Chronic aspirin use suppresses CDH1 methylation in human gastric mucosa.
AB  - There have been reports showing a protective role of aspirin and other
      nonsteroidal anti-inflammatory drugs (NSAIDs) against gastrointestinal cancers. E
      cadherin (CDH1) is an adhesion molecule involved in tumour invasion/metastasis.
      Silencing of CDH1 by promoter CpG island methylation was shown in gastric cancer,
      precancerous lesion, and Helicobacter pylori-infected chronic gastritis. We
      investigated the methylation status of CDH1 in noncancerous gastric mucosa in
      chronic aspirin user, and assessed its effect on methylation-associated
      carcinogenesis. Gastric mucosa samples from antrum were obtained from 217 cancer
      free subjects, including 37 chronic aspirin users and 180 subjects with no
      history of chronic or occasional intake of aspirin. Methylation-specific
      polymerase chain reaction (PCR), i.e., MSP, was performed for CDH1 gene promoter.
      In all 217 subjects, CDH1 methylation was detected for 69 subjects (31.7%). CDH1
      methylation more frequently occurred in H. pylori-infection-positive subjects (P
      < 0.0001), while chronic aspirin users had a significantly lower risk of CDH1
      methylation [nonuser versus user 36.1% versus 10.8%; odds ratio (OR) = 0.21, 95%
      confidence interval (CI) = 0.07-0.63, P = 0.005]. Logistic regression analysis
      showed that chronic aspirin use was the independent factor for lower risk of CDH1
      methylation (adjusted OR = 0.21, 95%CI = 0.07-0.66, P = 0.008). Chronic aspirin
      use was associated with lower risk of CDH1 methylation in H. pylori-positive
      subjects (nonuser versus user 49.5% versus 19.0%; OR = 0.24, 95%CI = 0.08-0.76, P
      = 0.01). Similar trend was also found in H. pylori-negative subjects (P = 0.07).
      No association was found between CDH1 methylation status, and duration and dose
      of aspirin. Our data suggest that chronic aspirin use is associated with reduced
      risk of CDH1 methylation in human gastric mucosa. Aspirin may have suppressive
      role against methylation-related gastric carcinogenesis.

PMID- 19184426
TI  - Whole-body insulin sensitivity index is a highly specific predictive marker for
      virological response to peginterferon plus ribavirin therapy in chronic hepatitis
      C patients with genotype 1b and high viral load.
AB  - Insulin resistance is a candidate predictive factor for virological response to
      peginterferon plus ribavirin (PEG/RBV) therapy in chronic hepatitis C patients.
      We examined whether indices of insulin resistance could serve as a predictor of
      sustained virological response (SVR). Fifty-one patients with genotype 1b and
      high viral load who received PEG/RBV therapy for 48 weeks were included.
      Homeostasis model assessment of insulin resistance (HOMA-IR) and whole-body
      insulin sensitivity index (WBISI) calculated from the 75-g oral glucose tolerance
      test and serum levels of soluble tumor necrosis factor receptor 2 (sTFNR2) were
      evaluated before therapy. Patients who achieved SVR had significantly lower HOMA
      IR and sTNFR2 levels and a higher WBISI compared with non-SVR patients. The
      positive predictive value for SVR was 0.653 for a HOMA-IR of <2 and 0.846 for a
      WBISI of 6 or higher. WBISI may serve as a highly specific predictor for SVR in
      PEG/RBV therapy.

PMID- 19184428
TI  - The effect of metoclopramide in capsule enteroscopy.
AB  - Clinical utility of prokinetics in capsule endoscopy (CE) is not clearly
      established. The objective of this prospective, randomized, single-blind,
      controlled trial was to determine if metoclopramide is useful in CE by increasing
      the rate of complete enteroscopy. Ninety-five patients referred for CE were
      randomized to no metoclopramide (group B, n = 48) or 10 mg metoclopramide (group
      A, n = 47). Complete enteroscopy was possible in 38 patients of group A (80.9%)
      and 37 of group B (77.1%) (P = 0.422) with two cases of gastric retention in
      group B (4.2%; P = 0.253). Median gastric transit time was 26 min (1-211) in
      group A and 28 min (4-200) in group B (P = 0.511). Mean small bowel transit time,
      calculated after excluding 20 patients with incomplete enteroscopy, was similar
      in both groups (221.2 +/- 89 min vs. 256 +/- 82.2 min; P = 0.083). There were
      also no differences in the total number of findings (group A 4.5 +/- 4.7; group B
      4.7 +/- 3.7, P = 0.815). Administration of 10 mg metoclopramide orally 15 min
      before capsule ingestion did not significantly increase the rate of total
      enteroscopies and had no effect on transit times. It also did not modify CE
      diagnostic yield.

PMID- 19184427
TI  - The discrepancy between genetic polymorphism of p53 codon 72 and the expression
      of p53 protein in Helicobacter pylori-associated gastric cancer in Korea.
AB  - The p53 gene has been referred to as 'the guardian of the genome' because it
      controls apoptosis and cell cycle arrest. The purpose of this study was to
      evaluate the association of p53 codon 72 genetic polymorphism and the p53
      immunohistochemistry with Helicobacter pylori-associated gastroduodenal diseases,
      including gastric cancer. This study included 1,852 subjects: controls and
      patients with gastric cancer, dysplasia, benign gastric ulcers, and duodenal
      ulcers (DU). Biallelic polymorphism was genotyped by restriction fragment length
      polymorphism. Immunohistochemical analysis for the detection of mutant type p53
      expression was performed. The frequency of the Pro/Pro allele of the p53 codon 72
      was higher in the patients with H. pylori-positive dysplasia than in controls
      (OR: 2.3, 95% CI: 1.3-4.3), but it was less frequent among patients with a H.
      pylori-positive DU (OR: 0.5, 95% CI: 0.3-0.8). However, there was no significant
      association with gastric cancer, including the location, stage, or histological
      type of gastric cancer. Expression of a mutant type of p53 protein was detected
      in 6.3% of dysplastic tissues and 26.5% of cancerous tissues compared 0% in the
      controls. Positive expression was higher in the intestinal type of cancer (34.9%)
      than in the diffuse type (15.0%; P = 0.001). These results suggest that genetic
      polymorphism of p53 codon 72 played a role in the determination of H. pylori
      associated gastroduodenal diseases, but p53 immunostaining did not correlate with
      those of the p53 genetic polymorphism analysis.

PMID- 19184429
TI  - Factors associated with symptom response to pyloric injection of botulinum toxin
      in a large series of gastroparesis patients.
AB  - Case series report symptom reductions after pyloric botulinum toxin injection in
      gastroparesis, but small controlled trials show no benefit. Factors that enhance
      response to therapy are undefined. A retrospective analysis of 179 gastroparetics
      undergoing pyloric botulinum toxin injection from 2001 to 2007 assessed responses
      relating to drug dosing, demographic factors, comorbidities, and gastric
      function. Overall, there was a decrease in gastroparetic symptoms 1-4 months
      after pyloric botulinum toxin injection in 92 patients (51.4%). Increasing the
      botulinum toxin dose significantly improved clinical responses of patients who
      provided information on symptoms after therapy (100 units: 54.2%; 200 units:
      76.7%; P=0.02). Other factors that improved response to botulinum toxin included
      female gender, age <50 years, and nondiabetic nonpostsurgical etiology (all
      P<0.05). Eighty-seven patients received 307 follow-up injections. A clinical
      response to a second injection was observed in 73.4% of evaluable patients. In
      conclusion, responses to pyloric botulinum toxin depended on dose and were
      maintained on repeat injection. Subgroup analyses defined subgroups likely to
      benefit. These findings provide the foundation for large, controlled trials of
      high-dose botulinum toxin in selected gastroparesis subsets.

PMID- 19184431
TI  - Mental health and other risk factors for jail incarceration among male veterans.
AB  - Data derived from the 2002 Survey of Inmates in Local Jails and the 2000 National
      Survey of Veterans show that having mental health problems in addition to such
      sociodemographic characteristics as being a member of a minority group, not being
      married, having less education, and being younger are risk factors for
      incarceration among veterans, as they are for the general population. As in
      previous studies veterans who served during the Vietnam Era and to an even
      greater extent, those who served in the early years of the All Volunteer Force
      were at greater risk of incarceration than veterans from the most recent period
      of the AVF, after controlling for age and other factors.

PMID- 19184432
TI  - Does the type of CIA policy significantly affect bar and restaurant employment in
      Minnesota cities?
AB  - Clean indoor air (CIA) policies that include free-standing bars and restaurants
      have been adopted by communities to protect employees in all workplaces from
      exposure to environmental tobacco smoke, most notably employees working in
      restaurants and free-standing bars. However, due to the perception of negative
      economic effects on alcohol-licensed hospitality businesses, partial CIA policies
      (those that provide an exemption for free-standing bars) have been proposed as a
      means to reduce the risk of economic effects of comprehensive CIA policies
      applied to all worksites. Bar and restaurant employment per capita were used to
      determine if partial CIA policies produced differential economic effects compared
      to comprehensive CIA policies. Ten cities in the state of Minnesota were studied
      from 2003-2006. Economic data were drawn from monthly employment in bars and
      restaurants, and a pooled time-series was completed to evaluate three types of
      local CIA policies: Comprehensive, partial, or none beyond the state law.
      Communities with a comprehensive CIA policy had a decrease of 9 employees per
      10,000 residents compared with communities with partial CIA policies (p = 0.10).
      Communities with any type of CIA policy (partial or comprehensive) had an
      increase of 3 employees per 10,000 residents compared to communities without any
      CIA policies (p = 0.36). There were no significant differential economic effects
      by CIA policy type in Minnesota cities. These findings support the adoption of
      comprehensive CIA policies to provide all employees protection from environmental
      tobacco smoke exposure.

PMID- 19184433
TI  - Kinetics of LFA-1 mediated adhesion of human neutrophils to ICAM-1--role of E
      selectin signaling post-activation.
AB  - LFA-1 and Mac-1 are the two integrins involved in the arrest and firm adhesion of
      neutrophils. LFA-1 plays a role in the early stage of cell arrest while Mac-1
      stabilizes firm adhesion. Here, we further elucidated the kinetics of LFA-1
      activation and its role in mediating neutrophil adhesion to ICAM-1 in the
      presence of E-selectin interaction. We confirm that LFA-1 activation to high
      affinity is transient in nature, decaying back to low affinity within 1 min after
      chemotactic stimulation. However, we show for the first time that this downshift
      in LFA-1 affinity does not return back to the low affinity state when E-selectin
      interaction is present and active, but rather E-selectin signals an intermediate
      LFA-1 conformation through PI3-Kinase that maintains an intermediate level of
      neutrophil firm adhesion. We further show that this E-selectin signaling is
      capable of returning LFA-1 to the intermediate affinity conformation outside the
      1-min window previously reported for LFA-1 functionality. While our work confirms
      a role for PI3-Kinase in neutrophil firm adhesion, we show that PI3-Kinase may
      not be important in the initial transition from rolling to firm arrest (i.e. LFA
      1 shift from low to high affinity conformation occurring within seconds of
      chemotactic stimulation).

PMID- 19184434
TI  - Human mesenchymal stem cells form multicellular structures in response to applied
      cyclic strain.
AB  - Mesenchymal stem cells (MSCs) are a component of many cardiovascular cell-based
      regenerative medicine therapies. There is little understanding, however, of the
      response of MSCs to mechanical cues present in cardiovascular tissues. The
      objectives of these studies were to identify a model system to study the effect
      of well-defined applied cyclic strain on MSCs and to use this system to determine
      the effect of cyclic equibiaxial strain on the cellular and cytoskeletal
      organization of MSCs. When exposed to 10%, 1 Hz cyclic equibiaxial strain for 48
      h, MSCs remained viable, retained characteristic gene and protein markers, and
      rearranged to form multicellular structures defined as clusters and knobs. This
      novel observation of cluster (overlapping cells surrounded by radial cellular
      projections) and knob (more dome-like structure containing significantly more
      cells than a cluster) formation did not involve changes in cytoskeletal proteins
      and resulted from cellular rearrangements initiated within 8 h of applied strain.
      Observed cellular responses were found to be dependent on substrate coating, but
      not on cell density for the 8-fold ranges tested. This system can thus be used to
      study the mechanoresponse over hours to days of MSCs exposed to applied cyclic
      strain in the context of cell-cell and cell-matrix interactions.

PMID- 19184435
TI  - Perfluorocarbon nanoemulsions for quantitative molecular imaging and targeted
      therapeutics.
AB  - A broad array of nanomaterials is available for use as contrast agents for
      molecular imaging and drug delivery. Due to the lack of endogenous background
      signal in vivo and the high NMR sensitivity of the (19)F atom, liquid
      perfluorocarbon nanoemulsions make ideal agents for cellular and magnetic
      resonance molecular imaging. The perfluorocarbon core material is surrounded by a
      lipid monolayer which can be functionalized with a variety of agents including
      targeting ligands, imaging agents and drugs either individually or in
      combination. Multiple copies of targeting ligands (approximately 20-40 monoclonal
      antibodies or 200-400 small molecule ligands) serve to enhance avidity through
      multivalent interactions while the composition of the particle's perfluorocarbon
      core results in high local concentrations of (19)F. Additionally, lipophilic
      drugs contained within molecularly targeted nanoemulsions can result in contact
      facilitated drug delivery to target cells. Ultimately, the dual use of
      perfluorocarbon nanoparticles for both site targeted drug delivery and molecular
      imaging may provide both imaging of disease states as well as conclusive evidence
      that drug delivery is localized to the area of interest. This review will focus
      on liquid perfluorocarbon nanoparticles as (19)F molecular imaging agents and for
      targeted drug delivery in cancer and cardiovascular disease.

PMID- 19184436
TI  - Biomolecular transport through hemofiltration membranes.
AB  - A theoretical model for filtration of large solutes through a pore in the
      presence of transmembrane pressures, applied/induced electric fields, and
      dissimilar interactions at the pore entrance and exit is developed to
      characterize and predict the experimental performance of a hemofiltration
      membrane with nanometer scale pores designed for a proposed implantable Renal
      Assist Device (RAD). The model reveals that the sieving characteristics of the
      membrane can be improved by applying an external electric field, and ensuring a
      smaller ratio of the pore-feed and pore-permeate equilibrium partitioning
      coefficients when diffusion is present. The model is then customized to study the
      sieving characteristics for both charged and uncharged solutes in the slit-shaped
      nanopores of the hemofiltration device for the RAD. The effect of streaming
      potential or induced fields are found to be negligible under representative
      operating conditions. Experimental data on the sieving coefficient of bovine
      serum albumin, carbonic anhydrase and thyroglobulin are reported and compared
      with the theoretical predictions. Both steric and electrostatic partitioning are
      considered and the comparison suggests that in general electrostatic effects are
      present in the filtration of proteins though some data, particularly those
      recorded in a strongly hypertonic solution (10x PBS), show better agreement with
      the steric partitioning theory.

PMID- 19184437
TI  - Religiosity, spirituality, and cancer fatalism beliefs on delay in breast cancer
      diagnosis in African American women.
AB  - African American women are more likely than any other racial or ethnic group to
      present with a later stage of breast cancer at initial diagnosis. Delay in breast
      cancer detection is a critical factor in diagnosis at a later stage. Available
      data indicate a delay of 3 months or more is a significant factor in breast
      cancer mortalty. Numerous factors have been reported as contributing to delay in
      time to seek medical care including religiosity, spirituality, and fatalistic
      beliefs. This study examined the influence of religiosity, spirituality, and
      cancer fatalism on delay in diagnosis and breast cancer stage in African American
      women with self-detected breast symptoms. A descriptive correlation,
      retrospective methodology using an open-ended questionnaire and three validated
      measurement scales were used: the Religious Problem Solving Scale (RPSS), the
      Religious Coping Activity Scale (RCAS) subscale measuring spiritually based
      coping, and the modified Powe Fatalism Inventory (mPFI). A convenience sample of
      129 women ages between 30 and 84 years who self-reported detecting a breast
      symptom before diagnosis of breast cancer within the preceding 12 months were
      included in the study. Outcome variables were time to seek medical care and
      breast cancer stage. Other variables of interest included marital status, income,
      education, insurance status, and to whom the women spoke about their breast
      symptoms. Data were analyzed using descriptive statistics, logistic regression
      analysis, Pearson r correlations, Mann-Whitney U analysis, and Chi Square
      analysis. Participants were found to be highly religious and spiritual but not
      fatalistic. While most women delayed more than 3 months in seeking medical care,
      no associations were found between the three predictor variables and time to seek
      medical care. The median delay in time from self detection of a breast symptom to
      seeking medical care was 5.5 months. Women who were less educated, unmarried, and
      talked to God only about their breast change were significantly more likely to
      delay seeking medical care. An association was found between disclosing a breast
      symptom to God only and delay in seeking medical care. In contrast, women who had
      told a person about their breast symptom were more likely to seek medical care
      sooner. African American women who delayed seeking medical care for longer than 3
      months were more likely to present with a later stage of breast cancer than women
      who sought care within 3 months of symptom discovery.

PMID- 19184438
TI  - Control of ER stress by a chemical chaperone counteracts apoptotic signals in IFN
      gamma-treated murine hepatocytes.
AB  - Apoptosis of hepatocytes plays a key role in the pathogenesis of immune-mediated
      hepatitis. However, the detailed mechanisms of apoptotic signaling remain
      unclear. In this study, we investigated the involvement of ER stress in a model
      of IFN-gamma-induced apoptosis of hepatocytes in vitro, using a chemical
      chaperone reagent, glycerol. IFN-gamma-induced apoptotic events (mitochondrial
      release of cytochrome c, enzymatic activation of caspase-3 and -9) were markedly
      inhibited by glycerol. Glycerol induced partial inhibition of cytotoxicity
      indicated by lactate dehydrogenase release from the cytosol but had no inhibitory
      effect on the induction of IRF-1 gene expression and reactive oxygen species,
      required for hepatocyte apoptosis by IFN-gamma. Induction of caspase-4 and -12
      gene expression, positively correlated with ER stress, was attenuated by
      glycerol. Gene analysis revealed that induction of ER stress-related genes, C/EBP
      homologue protein (CHOP/GADD153) and TRB3, was suppressed completely by glycerol
      treatment. These results suggest that ER stress plays a crucial role in mediating
      apoptosis of hepatocytes induced by IFN-gamma, and a chemical chaperone is an
      effective inhibitor of the ER stress.

PMID- 19184439
TI  - Editorial: Hello, goodbye.

PMID- 19184441
TI  - Typologies of alcohol dependence. From Jellinek to genetics and beyond.
AB  - The goal of typology research is to identify subtypes of alcohol dependent (AD)
      patients sharing fundamental characteristics and try to match each subtype, with
      the most precise treatment strategy. This review provides a comprehensive history
      of the literature on alcohol dependent subtypes starting from the earliest
      attempt made by Jellinek. The binary models identified most closely with
      Cloninger and Babor as well as the successively more complex classifications are
      discussed. Typology classification potentially useful in guiding the treatment of
      AD patients, especially in the case of the serotonergic medications. Contrasting
      data suggests that other factors could influence the response to a medication
      and/or that more complex typologies should be identified. In summary, typology
      models may assist in the ascertainment criteria for clinical trials performed in
      behavioral and pharmacotherapeutic interventions. Greater emphasis, however, must
      be made to more clearly delineate this field of research, while moving toward
      more standardized typologies.

PMID- 19184442
TI  - Compensated living kidney donation: a plea for pragmatism.
AB  - Kidney transplantation is the most efficacious and cost-effective treatment for
      end-stage renal disease. However, the treatment's accessibility is limited by a
      chronic shortage of transplantable kidneys, resulting in the death of numerous
      patients worldwide as they wait for a kidney to become available. Despite the
      implementation of various measures the disparity between supply and needs
      continues to grow. This paper begins with a look at the current treatment
      options, including various sources of transplantable kidneys, for end-stage renal
      disease. We propose, in accordance with others, the introduction of compensated
      kidney donation as a means of addressing the current shortage. We briefly outline
      some of the advantages of this proposal, and then turn to examine several of the
      ethical arguments usually marshaled against it in a bid to demonstrate that this
      proposal indeed passes the ethics test. Using available data of public opinions
      on compensated donation, we illustrate that public support for such a program
      would be adequate enough that we can realistically eliminate the transplant
      waiting list if compensation is introduced. We urge a pragmatic approach going
      forward; altruism in living kidney donation is important, but altruism only is an
      unsuccessful doctrine.

PMID- 19184443
TI  - Embodiment and chronic pain: implications for rehabilitation practice.
AB  - Throughout the Western world people turn towards the health care system seeking
      help for a variety of psychosomatic/psychosocial health problems. They become
      "patients" and find themselves within a system of practises that conceptualizes
      their bodies as "objective" bodies, treats their ill health in terms of the
      malfunctioning machine, and compartmentalizes their lived experiences into
      medically interpreted symptoms and signs of underlying biological dysfunction.
      The aim of this article is to present an alternative way of describing ill health
      and rehabilitation using the philosophy of Maurice Merleau-Ponty in order to
      deepen our understanding of the rehabilitation process. I will explore how the
      experience of chronic pain ruptures the natural connection between body and world
      and how the rehabilitation process can be understood as the re-insertion of the
      body into the flow of experience, where the body "disappears" into its natural
      silence in order to allow the world to once again unfold. The experience of
      chronic pain places the painful body in focus, resulting in a diminished
      articulation of both self and world. Persons with illness suffer not only from
      the physical aspects of pain and discomfort but also from a loss of identity
      where one feels alienated and detached from things that used to give meaning to
      ones life. Rehabilitation must not only address the material (medical) body but
      also the diminished sense of self as well as the retreat from the world outside
      of the painful body.

PMID- 19184444
TI  - Shared decision making, paternalism and patient choice.
AB  - In patient centred care, shared decision making is a central feature and widely
      referred to as a norm for patient centred medical consultation. However, it is
      far from clear how to distinguish SDM from standard models and ideals for medical
      decision making, such as paternalism and patient choice, and e.g., whether
      paternalism and patient choice can involve a greater degree of the sort of
      sharing involved in SDM and still retain their essential features. In the
      article, different versions of SDM are explored, versions compatible with
      paternalism and patient choice as well as versions that go beyond these
      traditional decision making models. Whenever SDM is discussed or introduced it is
      of importance to be clear over which of these different versions are being
      pursued, since they connect to basic values and ideals of health care in
      different ways. It is further argued that we have reason to pursue versions of
      SDM involving, what is called, a high level dynamics in medical decision-making.
      This leaves four alternative models to choose between depending on how we balance
      between the values of patient best interest, patient autonomy, and an effective
      decision in terms of patient compliance or adherence: Shared Rational
      Deliberative Patient Choice, Shared Rational Deliberative Paternalism, Shared
      Rational Deliberative Joint Decision, and Professionally Driven Best Interest
      Compromise. In relation to these models it is argued that we ideally should use
      the Shared Rational Deliberative Joint Decision model. However, when the patient
      and professional fail to reach consensus we will have reason to pursue the
      Professionally Driven Best Interest Compromise model since this will best
      harmonise between the different values at stake: patient best interest, patient
      autonomy, patient adherence and a continued care relationship.

PMID- 19184445
TI  - The implications of microsurgical anatomy for surgical approaches to the sellar
      region.
AB  - The knowledge of the normal anatomy and variations regarding the management of
      tumors of the sellar region is paramount to perform safe surgical procedures. The
      sellar region is located in the center of the middle cranial fossa; it contains
      complex anatomical structures, and is the site of various pathological processes:
      tumor, vascular, developmental, and neuroendocrine. We review the microsurgical
      anatomy (microscopic and endoscopic) of this region and discuss the surgical
      nuances regarding this topic, based on anatomical concepts.

PMID- 19184446
TI  - Ancillary benefits for caregivers of children with asthma participating in an
      environmental intervention study to alleviate asthma symptoms.
AB  - Providing care for children with asthma can be demanding and time-intensive with
      far-reaching effects on caregivers' lives. Studies have documented childhood
      asthma symptom reductions and improved asthma-related quality of life (AQOL) with
      indoor allergen-reducing environmental interventions. Few such studies, however,
      have considered ancillary benefits to caregivers or other family members.
      Ancillary benefits could be derived from child health improvements and reduced
      caregiving burden or from factors such as improved living environments or social
      support that often accompanies intensive residential intervention efforts. As
      part of the Boston Healthy Public Housing Initiative (HPHI), a longitudinal
      single-cohort intervention study of asthmatic children, we examined trends in
      caregivers' quality of life related to their child's asthma (caregiver AQOL)
      using monthly Juniper Caregiver Asthma Quality of Life Questionnaires (AQLQ) for
      32 primary caregivers to 42 asthmatic children aged 4 to 17 years. Longitudinal
      analyses were used to examine caregiver AQOL trends and their relationship to the
      child's AQOL, then to consider additional predictors of caregiver AQOL. Caregiver
      AQLQ improved significantly over the course of the study with overall
      improvements significantly correlated with child AQOL (p = 0.005). However,
      caregiver AQOL improved most in the months before environmental interventions,
      while children's AQOL improved most in the months following. Time trends in
      caregiver AQOL, controlling for child AQOL, were not explained by available
      social support or caregiver stress measures. Our findings suggest potential
      participation effects not adequately captured by standard measures. Future
      environmental intervention studies should more formally consider social support
      and participation effects for both children and caregivers.

PMID- 19184447
TI  - Hepatitis B virus infection in US correctional facilities: a review of diagnosis,
      management, and public health implications.
AB  - Among the blood-borne chronic viral infections, hepatitis B virus (HBV) infection
      is one that is not only treatable but also preventable by provision of
      vaccination. Despite the availability of HBV vaccine for the last 15 years, more
      than 1.25 million individuals in the USA have chronic HBV infection, and about
      5,000 die each year from HBV-related complications. From a societal perspective,
      access to treatment of chronic viral infections, like HIV and viral hepatitis, is
      highly cost-effective and has lasting benefits by reducing risk behaviors,
      morbidity, mortality, as well as disease transmission in the community.
      Individuals in correctional facilities are specially predisposed to such chronic
      viral infections because of their high-risk behaviors. The explosion of
      incarceration in the USA over the last few decades and the disproportionate
      burden of morbidity and mortality from chronic infections among the incarcerated
      have put incredible strains on an overcrowded system that was not originally
      designed to provide comprehensive medical care for chronic illnesses. Recently,
      there has been a call to address medical care for individuals with chronic
      medical conditions in correctional settings, including those with infectious
      diseases. The economic and public health burden of chronic hepatitis B and its
      sequelae, including cirrhosis and hepatocellular carcinoma, is felt most
      prominently in managed care settings with limited budgets, like correctional
      facilities. Prevalence of HBV infection among the incarcerated in the USA is
      fivefold that of the general population. We present a review of diagnosis,
      prevention, and the recently streamlined treatment guidelines for management of
      HBV infection in correctional settings, and discuss the implications and public
      health impact of these measures.

PMID- 19184448
TI  - An evaluation of an initiative to improve coordination and service delivery of
      homeless services networks.
AB  - This study examines system changes associated with the implementation of the
      Collaborative Initiative to Help End Chronic Homelessness, an 11-site multi
      agency intervention for chronically homeless adults. Data obtained from key
      informants on community-level interventions and interorganizational relationships
      were gathered from an average of 6.6 agencies at each site in four yearly waves.
      Hierarchical linear modeling was used to examine time trends and bivariate
      relationships between measures. There were significant increases over the full
      study period in the use of practices designed to encourage system integration, as
      well as in interorganizational measures of joint planning and coordination, and
      of trust and respect, although in later waves of the study these measures leveled
      off. There were also highly significant and positive cross-sectional associations
      between the use of practices designed to encourage system integration and direct
      measures of service system integration as well as between measures of change in
      these system characteristics.

PMID- 19184449
TI  - Crystal morphology engineering of pharmaceutical solids: tabletting performance
      enhancement.
AB  - Crystal morphology engineering of a macrolide antibiotic, erythromycin A
      dihydrate, was investigated as a tool for tailoring tabletting performance of
      pharmaceutical solids. Crystal habit modification was induced by using a common
      pharmaceutical excipient, hydroxypropyl cellulose, as an additive during
      crystallization from solution. Observed morphology of the crystals was compared
      with the predicted Bravais-Friedel-Donnay-Harker morphology. An analysis of the
      molecular arrangements along the three dominant crystal faces [(002), (011), and
      (101)] was carried out using molecular simulation and thus the nature of the host
      additive interactions was deduced. The crystals with modified habit showed
      improved compaction properties as compared with those of unmodified crystals.
      Overall, the results of this study proved that crystal morphology engineering is
      a valuable tool for enhancing tabletting properties of active pharmaceutical
      ingredients and thus of utmost practical value.

PMID- 19184450
TI  - Studies on mefenamic acid microparticles: formulation, in vitro release, and in
      situ studies in rats.
AB  - In this study, we investigated the in vitro characteristics of mefenamic acid
      (MA) microparticles as well as their effects on DNA damage. MA-loaded chitosan
      and alginate beads were prepared by the ionotropic gelation process. Microsponges
      containing MA and Eudragit RS 100 were prepared by quasi-emulsion solvent
      diffusion method. The microparticles were characterized in terms of particle
      size, surface morphology, encapsulation efficiency, and in vitro release
      profiles. Most of the formulation variables manifested an influence on the
      physical characteristics of the microparticles at varying degrees. We also
      studied the effects of MA, MA-loaded microparticles, and three different polymers
      on rat brain cortex DNA damage. Our results showed that DNA damage was higher in
      MA-loaded Eudragit microsponges than MA-loaded biodegradable chitosan or alginate
      microparticles.

PMID- 19184451
TI  - Predicting pharmacokinetics of drugs using physiologically based modeling-
      application to food effects.
AB  - Our knowledge of the major mechanisms underlying the effect of food on drug
      absorption allows reliable qualitative prediction based on biopharmaceutical
      properties, which can be assessed during the pre-clinical phase of drug
      discovery. Furthermore, several recent examples have shown that physiologically
      based absorption models incorporating biorelevant drug solubility measurements
      can provide quite accurate quantitative prediction of food effect. However, many
      molecules currently in development have distinctly sub-optimal biopharmaceutical
      properties, making the quantitative prediction of food effect for different
      formulations from in vitro data very challenging. If such drugs reach clinical
      development and show undesirable variability when dosed with food, improved
      formulation can help to reduce the food effect and carefully designed in vivo
      studies in dogs can be a useful guide to clinical formulation development. Even
      so, such in vivo studies provide limited throughput for screening, and food
      effects seen in dog cannot always be directly translated to human. This paper
      describes how physiologically based absorption modeling can play a role in the
      prediction of food effect by integrating the data generated during pre-clinical
      and clinical research and development. Such data include physicochemical and in
      vitro drug properties, biorelevant solubility and dissolution, and in vivo pre
      clinical and clinical pharmacokinetic data. Some background to current
      physiological absorption models of human and dog is given, and refinements to
      models of in vivo drug solubility and dissolution are described. These are
      illustrated with examples using GastroPlus to simulate the food effect in dog and
      human for different formulations of two marketed drugs.

PMID- 19184453
TI  - Sources of information and health beliefs related to SARS and avian influenza
      among Chinese communities in the United Kingdom and The Netherlands, compared to
      the general population in these countries.
AB  - BACKGROUND: Ethnic minorities in Europe such as the Chinese may need a special
      strategy with regard to risk communication about emerging infectious diseases. To
      engage them in precautionary actions, it is important to know their information
      sources, knowledge, and health beliefs. PURPOSE: This study's purpose is to study
      the use of information sources, knowledge, and health beliefs related to SARS and
      avian flu of Chinese people in the UK and The Netherlands, and to make
      comparisons with the general population in these countries. METHOD: Results of a
      self-administered questionnaire among 300 British/Dutch Chinese were compared to
      data obtained from a computer-assisted phone survey among the general population
      (n = 800). RESULTS: British/Dutch Chinese got most information about emerging
      diseases from family and friends, followed by Chinese media and British/Dutch TV.
      They had less confidence than general groups in their doctor, government
      agencies, and consumer/patient interest groups. Their knowledge of SARS was high.
      They had a lower perceived threat than general populations with regard to SARS
      and avian flu due to a lower perceived severity. They had higher self-efficacy
      beliefs regarding SARS and avian flu. CONCLUSION: In case of new outbreaks of
      SARS/avian flu in China, local authorities in the UK and The Netherlands can best
      reach Chinese people through informal networks and British/Dutch TV, while trying
      to improve confidence in information from the government. In communications, the
      severity of the disease rather than the susceptibility appears to need most
      attention.

PMID- 19184454
TI  - Acyl migration during deacylation of phospholipids rich in docosahexaenoic acid
      (DHA): an enzymatic approach for evidence and study.
AB  - Non-enzymatic acyl migration could be counter-productive for the preparation of
      structured phospholipids with docosahexaenoic acid (DHA) at a designated
      position. Therefore enzymatic approaches have been developed to investigate acyl
      migration. First, acyl migration from sn-2 to sn-1 position has been set into
      relief by a three step enzymatic method using a typo-selective lipase, a
      phospholipase A2 and a non-selective lipase. The effect of reaction temperature
      on acyl migration from sn-2 to sn-1 was monitored: lowering the reaction
      temperature from 40 to 30 degrees C allowed a reduction of DHA migration rate of
      40%. Secondly, acyl migration from sn-1 to sn-2 position was negligible. This
      last result was obtained through the study of structured phosphatidylcholine
      selective deacylation using a phospholipase A2.

PMID- 19184452
TI  - Targeting fatty acid amide hydrolase (FAAH) to treat pain and inflammation.
AB  - The endogenous cannabinoid N-arachidonoyl ethanolamine (anandamide; AEA) produces
      most of its pharmacological effects by binding and activating CB(1) and CB(2)
      cannabinoid receptors within the CNS and periphery. However, the actions of AEA
      are short lived because of its rapid catabolism by fatty acid amide hydrolase
      (FAAH). Indeed, FAAH knockout mice as well as animals treated with FAAH
      inhibitors are severely impaired in their ability to hydrolyze AEA as well as a
      variety of noncannabinoid lipid signaling molecules and consequently possess
      greatly elevated levels of these endogenous ligands. In this mini review, we
      describe recent research that has investigated the functional consequences of
      inhibiting this enzyme in a wide range of animal models of inflammatory and
      neuropathic pain states. FAAH-compromised animals reliably display
      antinociceptive and anti-inflammatory phenotypes with a similar efficacy as
      direct-acting cannabinoid receptor agonists, such as Delta(9)
      tetrahydrocannabinol (THC), the primary psychoactive constituent of Cannabis
      sativa. Importantly, FAAH blockade does not elicit any apparent psychomimetic
      effects associated with THC or produce reinforcing effects that are predictive of
      human drug abuse. The beneficial effects caused by FAAH blockade in these models
      are predominantly mediated through the activation of CB(1) and/or CB(2)
      receptors, though noncannabinoid mechanisms of actions can also play contributory
      or even primary roles. Collectively, the current body of scientific literature
      suggests that activating the endogenous cannabinoid system by targeting FAAH is a
      promising strategy to treat pain and inflammation but lacks untoward side effects
      typically associated with Cannabis sativa.

PMID- 19184455
TI  - Explicitly accounting for pixel dimension in calculating classical and fractal
      landscape shape metrics.
AB  - Different summarized shape indices, like mean shape index (MSI) and area weighted
      mean shape index (AWMSI) can change over multiple size scales. This variation is
      important to describe scale heterogeneity of landscapes, but the exact
      mathematical form of the dependence is rarely known. In this paper, the use of
      fractal geometry (by the perimeter and area Hausdorff dimensions) made us able to
      describe the scale dependence of these indices. Moreover, we showed how fractal
      dimensions can be deducted from existing MSI and AWMSI data. In this way, the
      equality of a multiscale tabulated MSI and AWMSI dataset and two scale-invariant
      fractal dimensions has been demonstrated.

PMID- 19184456
TI  - Mathematical modeling of intrusive growth of fusiform initials in relation to
      radial growth and expanding cambial circumference in Pinus sylvestris L.
AB  - This study on the cambium of Pinus sylvestris L. examines the intrusive growth of
      fusiform cambial initials and its possible contribution to the tangential and
      radial expansions of the cambial cylinder. The location and extent of intrusive
      growth of the fusiform initials were determined by microscopic observations and
      by mathematical modeling. In order to meet the required circumferential expansion
      of the cambial cylinder, the fusiform initials grow in groups by means of a
      symplastic rather than intrusive growth, leaving no room for the assumption that
      intrusive growth of the initials takes place between radial walls and has a
      direct role in the increase of the cambial circumference. Therefore, it is
      postulated that the fusiform initials grow intrusively between the tangential
      walls of the neighboring initials and their immediate derivatives and not between
      the radial walls of the adjacent initials as per common belief.

PMID- 19184457
TI  - Gadolinium promoted proliferation and enhanced survival in human cervical
      carcinoma cells.
AB  - The effect of gadolinium chloride (Gd) on the proliferation of HeLa cells was
      investigated at lower concentration. The results obtained by MTT and cell cycle
      analysis showed that Gd promoted proliferation by inducing S phase entry in HeLa
      cells at the concentration less than 100 microM. It was further evidenced by both
      an increase in the levels of phosphorylation of retinoblastoma protein (pRb) and
      a remarkable increase in cyclin E expression. Moreover, the survival of cells,
      exposed to Gd up to 3-5 days, was increased compared with control. The
      attenuation of the serum deprivation-induced cell loss by Gd was associated with
      the sustained activation of FAK (PY(397)) and the delayed activation of JNKs
      pathway. Besides, it appeared that Gd promoted cell proliferation and survival in
      HeLa cells was not contributed to the ROS generation. Based on the present
      results, both positive and negative effects of the lanthanides as potential drugs
      or diagnostic agents are discussed.

PMID- 19184458
TI  - Siderocalins: siderophore-binding proteins of the innate immune system.
AB  - Recent studies have revealed that the mammalian immune system directly interferes
      with siderophore-mediated iron acquisition through siderophore-binding proteins
      and that the association of certain siderophores, or siderophore modifications,
      with virulence is a direct response of pathogens to evade these defenses.

PMID- 19184459
TI  - Novel antisense oligonucleotides containing hydroxamate linkages: targeted iron
      triggered chemical nucleases.
AB  - Antisense oligonucleotides with iron binding hydroxamate linkages are designed to
      act as sequence-selective cleaving agents of complementary nucleic acids through
      Fenton chemistry. Oligothymidylate analogs with hydroxamate linkages were
      efficiently synthesized from coupling of nucleoside intermediates, activated as p
      nitrophenyl carbonates, with hydroxylamine derivatized nucleosides. Iron binding
      studies showed that hydroxamate linked oligonucleotides are effective iron
      chelators when there are three nonadjacent internucleosidic hydroxamate linkages
      available in the same oligonucleotide molecule. However, analysis of the CD
      spectra of an oligothymidylate 16mer, which contained complete substitution of
      all phosphates with hydroxamates, indicated that the hydroxamate linkage was too
      rigid to allow the analog to base pair with the complementary DNA d(A(16)).
      Syntheses of mix-linked thymidine oligomers with up to three hydroxamate linkages
      incorporated in the center of the sequence are also reported. Iron binding of the
      thymidine oligomer with hydroxamate linkages was confirmed by matrix assisted
      laser desorption mass spectrometry analysis. Nuclease stability assays showed
      that the modified oligonucleotides have enhanced resistance toward nuclease S1
      (endonuclease) compared to natural oligonucleotides. A thymidine 16mer with three
      hydroxamate linkages incorporated in the center of the sequence was shown to be
      able to bind with both iron and its complementary polyA strand. A small
      destablizing effect was observed when the phosphodiester linkage was changed to
      the hydroxamate linkage. Under Fenton chemistry conditions, this novel iron
      binding oligothymidylate analog cleaved the complementary DNA strand sequence
      selectively.

PMID- 19184461
TI  - Transcript profiling of oilseed rape (Brassica napus) primed for biocontrol
      differentiate genes involved in microbial interactions with beneficial Bacillus
      amyloliquefaciens from pathogenic Botrytis cinerea.
AB  - Many microorganisms interact with plants but information is insufficient
      concerning requirements for plant colonization and if interactions become
      beneficial or detrimental. Pretreatment of oilseed rape (Brassica napus) with
      Bacillus results in disease suppression upon challenge with pathogens. We have
      studied transcriptome effects on oilseed rape primed with the Bacillus
      amyloliquefaciens 5113 biocontrol strain and compared that with effects of the
      fungal pathogen Botrytis cinerea. Using the cDNA-AFLP technique 21,700 transcript
      fragments were obtained of which 120 were differentially expressed and verified
      by northern blot analysis for selected transcripts. Priming with Bacillus caused
      greater effect on leaf than root transcripts where sequencing and BLAST analysis
      suggested many of the transcripts to be involved in metabolism and bioenergy.
      Bacillus and Botrytis treatment also changed metabolic gene expression in
      addition to signaling and transcription control genes as well as a potential
      disease resistance (TIR-NBS-LRR) gene. The pathogen provoked non-primed plant
      profile was less dominated by metabolism than Bacillus and Bacillus-Botrytis
      treated plants. Several transcripts were homologues to unknown genes in the
      different treatments. Altogether Bacillus treatment of roots cause a systemic
      gene expression in leaves suggested to result in a metabolic reprogramming as a
      major event during priming.

PMID- 19184460
TI  - Structural characterization of Brachypodium genome and its syntenic relationship
      with rice and wheat.
AB  - Brachypodium distachyon (Brachypodium) has been recently recognized as an
      emerging model system for both comparative and functional genomics in grass
      species. In this study, 55,221 repeat masked Brachypodium BAC end sequences (BES)
      were used for comparative analysis against the 12 rice pseudomolecules. The
      analysis revealed that approximately 26.4% of BES have significant matches with
      the rice genome and 82.4% of the matches were homologous to known genes. Further
      analysis of paired-end BES and approximately 1.0 Mb sequences from nine selected
      BACs proved to be useful in revealing conserved regions and regions that have
      undergone considerable genomic changes. Differential gene amplification,
      insertions/deletions and inversions appeared to be the common evolutionary events
      that caused variations of microcolinearity at different orthologous genomic
      regions. It was found that approximately 17% of genes in the two genomes are not
      colinear in the orthologous regions. Analysis of BAC sequences also revealed
      higher gene density (approximately 9 kb/gene) and lower repeat DNA content
      (approximately 13.1%) in Brachypodium when compared to the orthologous rice
      regions, consistent with the smaller size of the Brachypodium genome. The 119
      annotated Brachypodium genes were BLASTN compared against the wheat EST database
      and deletion bin mapped wheat ESTs. About 77% of the genes retrieved significant
      matches in the EST database, while 9.2% matched to the bin mapped ESTs. In some
      cases, genes in single Brachypodium BACs matched to multiple ESTs that were
      mapped to the same deletion bins, suggesting that the Brachypodium genome will be
      useful for ordering wheat ESTs within the deletion bins and developing specific
      markers at targeted regions in the wheat genome.

PMID- 19184462
TI  - Parental relatedness and major histocompatibility effects on early embryo
      survivorship in Atlantic salmon.
AB  - Salmon have provided key insights into the relative influence of natural and
      sexual selection on major histocompatibility complex (MHC) variation. Natural
      selection on salmon MHC genes has been demonstrated in pathogen studies, and
      there is evidence of MHC-based mate choice (sexual selection). We tested whether
      parental MHC genes affect survivorship of juvenile Atlantic salmon (Salmo salar)
      by quantifying the influence of parental genome-wide relatedness and MHC genotype
      on survivorship to the swim-up stage. Thirteen microsatellite loci were used to
      estimate the influence of genome-wide relatedness between parents on offspring
      survivorship and MHC genotypes were determined by sequencing part of the class
      IIbeta gene. Our results revealed no significant relationship between early
      offspring survivorship and genome-wide relatedness, predicted MHC heterozygosity,
      or MHC allelic similarity. Overall, our data are consistent with the contention
      that excess MHC heterozygosity in Atlantic salmon juveniles is due to sexual
      selection as well as differential survival of offspring due to MHC genotype.

PMID- 19184463
TI  - Infestation of a novel host plant by Tephritis conura (Diptera: Tephritidae) in
      northern Britain: host-range expansion or host shift?
AB  - The addition of a novel host plant to a phytophagous insect's diet may result in
      subsequent host-plant specialisation, and is believed to be a key cause for
      speciation in this trophic group. In northern Britain, the tephritid fly
      Tephritis conura has experienced a unique host-plant expansion, from the
      melancholy thistle Cirsium heterophyllum to the marsh thistle C. palustre. Here,
      we examine whether the incorporation of C. palustre in the repertoire of British
      T. conura flies has caused genetic divergence between populations infesting the
      old host and the novel host, and how British populations differ from populations
      infesting C. heterophyllum in continental Europe where C. palustre is not
      infested. No evidence for restricted gene flow among British C. palustre and C.
      heterophyllum flies was found. Significant differentiation between British and
      continental T. conura was found at only one allozyme locus, hexokinase, and
      caused by a new allele, Hex_95. Hexokinase is related to host-race formation in
      continental European flies infesting C. heterophyllum and C. oleraceum, and might
      be linked to loci determining host choice. Based on morphological and
      phenological data from previous studies, we suggest that T. conura in Britain has
      adapted to the novel host but that host-race formation is impeded by similar
      plant phenologies.

PMID- 19184464
TI  - Body mass index and mortality: results of a cohort of 184,697 adults in Austria.
AB  - There is still a debate about the role of body mass index (BMI) as a risk factor
      for all-cause mortality. Most investigations with large sample sizes focused on
      populations from the United States, studies from Central-European cohorts are not
      available. We investigated the association between BMI and all-cause mortality
      and cause-specific mortality within a cohort in Austria. Design of this article
      is "Cohort study". The Subjects used were 184,697 men and women (mean age 41.7 +/
      15.4 years). Weight and height were measured. Cox proportional hazards models
      were used to estimate hazard ratios (HR). During a median follow-up of 15.1 years
      15,557 deaths (6,077 from cardiovascular disease, 4,443 from cancer and 606 from
      respiratory disease) were seen. A U-shaped association between BMI and all-cause
      mortality was observed in men and women. Compared with the reference category
      (BMI 22.5-24.9 kg/m(2)) high risks were found both in the highest category of BMI
      (> or =35 kg/m(2)) with HR of 2.13 (95% CI, 1.82-2.48) in men and 1.60 (95% CI,
      1.42-1.81) in women and in the lowest category (<18.5 kg/m(2)) with HR of 2.57
      (95% CI, 2.17-3.05) in men and 1.40 (95% CI, 1.21-1.62) in women. Similar
      patterns were seen among ever-smokers and non-smokers. Increased mortality with
      increasing BMI was driven by cardiovascular diseases and to a lesser extent by
      cancers. Respiratory diseases contributed to mortality in the lowest BMI category
      independently from smoking status. Underweight and obesity were both associated
      with higher all-cause mortality in men and women.

PMID- 19184466
TI  - The testing of antibodies raised against poultry red mite antigens in an in vitro
      feeding assay; preliminary screen for vaccine candidates.
AB  - Dermanyssus gallinae (De Geer), the poultry red mite, is a blood-feeding
      ectoparasite that infests many bird species. We have used an in vitro feeding
      assay to allow the identification of protective D. gallinae antigens that may
      have potential as vaccine candidates. Homogenised mites were extracted
      sequentially with PBS, Tween 20, Triton X100 and urea giving four protein
      fractions. Five experimental groups of Lohmann Brown hens were used to generate
      antibodies; four groups were injected with one of each of the protein fractions
      in QuilA adjuvant and a control group was injected with adjuvant only. Booster
      injections were administered 2 and 4 weeks after initial immunisation. Eggs were
      collected throughout the experiment and soluble IgY antibodies were extracted
      from a pool of egg yolks collected at week six post-injection. Western blots,
      performed using post vaccination antibodies from test and control groups,
      revealed a strong antibody response against a range of injected proteins. Fresh
      chicken blood, supplemented with antibodies raised against these protein
      fractions, was fed to mites in an in vitro feeding assay in order to determine
      whether the antibodies had an anti-mite effect. Although there was variability in
      the numbers of feeding mites, it was found that the strongest anti-mite effect
      was seen with the PBS protein fraction, which had a cumulative average mortality
      of 34.8% 14 days after feeding compared with 27.3% for the control group (P =
      0.043).

PMID- 19184465
TI  - Effect of vaccination with a recombinant metalloprotease from Haemaphysalis
      longicornis.
AB  - We report the cloning, expression and characterization of an Haemaphysalis
      longicornis metalloprotease (named HLMP1). The gene encodes a predicted 550
      aminoacid protein with similarity to metalloproteases of the reprolysin family.
      The protein sequence contains a signal sequence, the zinc-binding motif
      (HEXXHXXGXXH) common to metalloproteases and a cysteine-rich region. Reverse
      transcription-PCR expression analysis indicates the presence of mRNA in the
      salivary gland of larva, nymph and adult ticks. Rabbit repeatedly infested with
      H. longicornis recognized rHLMP1, suggesting that the immune-response against
      HLMP1 is naturally induced through the feeding of ticks. Vaccination of rabbit
      with rHLMP1 produced protective immunity against ticks, resulting in 15.6 and
      14.6% mortality in nymph and adult ticks, respectively. This work provides
      information to understand the tick's defense system, and offers new insights to
      develop strategies to block this defense system with an anti-tick vaccine based
      on a metalloprotease.

PMID- 19184467
TI  - The influence of sublethal deposits of agricultural mineral oil on the functional
      and numerical responses of Phytoseiulus persimilis (Acari: Phytoseiidae) to its
      prey, Tetranychus urticae (Acari: Tetranychidae).
AB  - Occasional pesticide application in integrated pest management to at least part
      of a crop requires that any biological control agents must re-invade previously
      sprayed areas in order that resurgent pests can be constrained. The ability of
      the phytoseiid predatory mite Phytoseiulus persimilis to feed on adult two
      spotted spider mite (TSSM) Tetranychus urticae on excised leaf discs in both
      control conditions and in a treatment with a sub lethal residue of agricultural
      mineral oil (AMO) was assessed. The predator exhibited a Type II functional
      response with the asymptote significantly higher in the AMO conditions due to the
      fact that the prey grew slower and reached a smaller size in this treatment. In
      terms of prey volume eaten, the satiation level of the predator was unchanged by
      the AMO deposits. The numbers of eggs produced by adult P. persimilis females at
      densities of 4, 8 and 16 TSSM adult females/disc in the control were
      significantly higher than those in the AMO treatment, but were similar for the
      higher density levels, 32 and 64 prey per disc. Thus the functional response in
      terms of volume of prey eaten explained the numerical response in terms of
      predator eggs produced. The presence of AMO deposits when the prey were at high
      density had no effect on predator efficiency (volume eaten) but resulted in a
      lower intake than that in control conditions when there was a greater distance
      between prey.

PMID- 19184468
TI  - Genetic variation in populations of Allothrombium pulvinum (Acari: Trombidiidae)
      from Northern Iran revealed by mitochondrial coxI and nuclear rDNA ITS2
      sequences.
AB  - Allothrombium pulvinum Ewing is a common natural enemy of aphids and some other
      arthropods. So far, there are no studies that have addressed genetic variation of
      this predatory mite. We investigated genetic variation of A. pulvinum across its
      whole known range in Iran. A 410 bp portion of the mitochondrial cytochrome c
      oxidase subunit I gene (coxI) and 797-802 bp portion of the internal transcribed
      spacer 2 of rDNA (ITS2) were sequenced for 55 individuals from 11 populations,
      resulting in 12 and 26 haplotypes, respectively. In the coxI region, haplotype
      and nucleotide diversities varied among populations from 0.00 to 0.90 and from
      0.0000 to 0.0110, respectively. In the ITS2 region they varied from 0.20 to 0.91
      and from 0.0006 to 0.0023, respectively. For both gene regions the highest
      haplotype and nucleotide diversities were detected in population Mahmoud Abad
      from northern Iran. Statistically significant population differentiation (F (ST))
      was detected in most pair-wise population comparisons. The results of population
      differentiation for both gene regions were generally congruent indicating that A.
      pulvinum from Iran consists of genetically different populations. This suggests
      that A. pulvinum comprises at least two geographically distinct populations or
      even more than one species. This study is an initial step towards understanding
      genetic variation of A. pulvinum, a taxon for which little molecular information
      is available. More intensive sampling and analysis of additional DNA regions are
      necessary for more detailed classification of this taxon.

PMID- 19184469
TI  - Candidate predators for biological control of the poultry red mite Dermanyssus
      gallinae.
AB  - The poultry red mite, Dermanyssus gallinae, is currently a significant pest in
      the poultry industry in Europe. Biological control by the introduction of
      predatory mites is one of the various options for controlling poultry red mites.
      Here, we present the first results of an attempt to identify potential predators
      by surveying the mite fauna of European starling (Sturnus vulgaris) nests, by
      assessing their ability to feed on poultry red mites and by testing for their
      inability to extract blood from bird hosts, i.e., newly hatched, young starlings
      and chickens. Two genuine predators of poultry red mites are identified:
      Hypoaspis aculeifer and Androlaelaps casalis. A review of the literature shows
      that some authors suspected the latter species to parasitize on the blood of
      birds and mammals, but they did not provide experimental evidence for these
      feeding habits and/or overlooked published evidence showing the reverse. We
      advocate careful analysis of the trophic structure of arthropods inhabiting bird
      nests as a basis for identifying candidate predators for control of poultry red
      mites.

PMID- 19184470
TI  - Phylogenetic relationship between Dermanyssus gallinae populations in European
      countries based on mitochondrial COI gene sequences.
AB  - Phylogenetic analysis of Dermanyssus gallinae mites originating from UK, France
      and Italy was performed using partial amplification of the mitochondrial COI
      gene. Results showed that UK samples reveal the greatest variation and diversity
      and are linked to one of the French populations highlighting North-South genetic
      transitions in European red mite populations. Intra-farm variations between mite
      samples highlighted the diversity between national populations and possibly its
      origin from the different chemical strategies used in each country.

PMID- 19184471
TI  - A morphological study on Leydig cells of scrotal hyperthermia applied rats in
      short-term.
AB  - Testicular function is highly dependent on temperature control. The aim of this
      study was designed to investigate the morphological changes and regulation of
      steroidogenesis by light and electron microscopic level in Leydig cells (LC)
      after scrotal hyperthermia in rats. The rats were randomly allotted into one of
      four experimental groups: A (Control), B (1 day after scrotal hyperthermia), C
      (14 days after scrotal hyperthermia), D (35 days after scrotal hyperthermia);
      each group contain seven animals. Scrotal hyperthermia was carried out in a
      thermostatically controlled water bath at 43 degrees C for 30 min once daily for
      6 consecutive days. Control rats were treated in the same way, except the testes
      were immersed in a water bath maintained at 22 degrees C. Hyperthermia applied
      rats were sacrificed under 50 mg/kg ketamine anaesthesia after 1, 14 and 35 days,
      and biopsy materials of testis were obtained for light and electron microscopic
      examinations. To date, no histopathological changes of LC injury after scrotal
      hyperthermia in rats have been reported. Light microscopic examinations indicated
      increase degenerative LC, decrease in number of testosterone positive LC in
      interstitial area after scrotal hyperthermia in short-term. In scrotal
      hyperthermia, a dilated smooth endoplasmic reticulum, swollen mitochondria, and
      vanished mitochondrial cristae were observed. The nuclei of some LC displayed
      deep invaginations and irregular outlines. The number of lipid droplets was very
      considerably increased in most LC when compared to control group. As a
      conclusion, we claim that temperatures higher than the body temperature may cause
      infertility by damaging LC.

PMID- 19184472
TI  - Serum total cholesterol and the risk of breast cancer in postmenopausal Korean
      women.
AB  - OBJECTIVE: To evaluate an association between serum total cholesterol level and
      breast cancer risk, for which inconsistent findings have been reported in spite
      of the role of serum cholesterol as a precursor to a breast cancer-related sex
      steroid hormone. METHODS: Postmenopausal Korean women (n = 170,374), categorized
      into four groups by quartiles of cholesterol level, were followed up for
      occurrence of breast cancer from 1993 to 2003. Relative risks were assessed by
      Cox proportional hazard analysis. RESULTS: A positive association between
      cholesterol level and breast cancer risk was found with 31% greater age-adjusted
      risk of breast cancer in the highest cholesterol group (>or=5.95 mmol/l) than
      that in the lowest cholesterol group (<4.63 mmol/l). The strength of association
      was reduced slightly but persisted after the adjustment for reproductive and
      behavioral covariates. However, the association further attenuated and the
      positive trend was no longer significant when BMI was additionally adjusted (p
      trend, 0.0684). Stratified analysis by BMI showed that the risk of breast cancer
      increased with increasing cholesterol level only in normal BMI (<25 kg/m(2))
      group, but the interaction term was not significant. CONCLUSION: Serum total
      cholesterol level is not associated with the risk of breast cancer in
      postmenopausal Korean women.

PMID- 19184473
TI  - Risk of cancer among rheumatoid arthritis patients in California.
AB  - OBJECTIVE: The objective of this retrospective cohort study was to evaluate
      cancer risk among rheumatoid arthritis (RA) patients in California. METHODS: The
      study cohort derived from statewide patient discharge records was followed via
      linkage with cancer registry data over the period 1991-2002. Age and sex adjusted
      standardized incidence ratios (SIRs) and 95% confidence intervals were calculated
      to compare observed to expected numbers of cancers based on age, race, and sex
      specific incidence rates in the California population. RESULTS: Among the 84,475
      RA patients, who were observed for 405,540 person-years, 5,533 incident cancers
      were diagnosed during the observation interval. The risk of developing
      lymphohematopoietic cancer was significantly higher in the cohort for both sexes.
      Males had significantly higher risks of lung, liver, and esophageal cancer, but a
      lower risk of prostate cancer. Females were at significantly decreased risk for
      several cancers including breast, ovary, uterus, cervix, and melanoma, with the
      risk reduction ranging from 15 to 57% lower than the general population.
      Hispanics had increased risks of leukemia, vagina/vulva, lung, and liver cancers.
      CONCLUSION: Studies investigating the mechanisms that underlie the reported
      associations between RA and specific cancer types are needed.

PMID- 19184474
TI  - Lung cancer in chrysotile asbestos workers: analyses based on the two-stage
      clonal expansion model.
AB  - OBJECTIVE: To evaluate the magnitude and temporal pattern of lung cancer risk
      following exposure to chrysotile asbestos. METHODS: I analyzed data on lung
      cancer mortality in a cohort of asbestos textile workers who were exposed to
      almost pure chrysotile. Employment history and industrial hygiene data were used
      to derive asbestos exposure estimates. These data were analyzed within the
      framework of the two-stage clonal expansion (TSCE) model and the Cox proportional
      hazards model. RESULTS: Under the TSCE model, the association between chrysotile
      asbestos and lung cancer mortality was primarily due to an exposure-induced
      increase in the proliferation of initiated cells. In a setting of protracted
      exposure to chrysotile asbestos, this model implies that the estimated hazard
      ratio was at its maximum between ages 40 and 65 years. Cox regression analyses
      support these conclusions; the estimated excess relative risk per fiber-year/ml
      was 0.053 (95% CI: 0.023, 0.124) at ages <65 years, while there was minimal
      evidence of association at older attained ages. CONCLUSIONS: The TSCE model fits
      these data well, accommodating the observed departure from the proportional
      hazards assumption. These analyses suggest that the effect of chrysotile asbestos
      exposure on lung cancer risk varies with attained age.

PMID- 19184475
TI  - Dose-response meta-analysis of silica and lung cancer.
AB  - OBJECTIVE: To examine the association between occupational exposure to silica and
      lung cancer from a systematic review (and meta-analysis) of the epidemiologic
      literature, with special reference to the methodological quality of observational
      studies. METHODS: We searched Medline, Toxline, BIOSIS, and Embase (1966-December
      2007) for original articles published in any language. Observational studies
      (cohort and case-control studies) were selected if they reported the result of
      dose-response analyses relating lung cancer to occupational exposure to silica
      after appropriate adjustment for smoking. RESULTS: Ten studies (4 cohort studies
      and 6 case-control studies) met the inclusion criteria of the meta-analysis, nine
      of which contributing to the main analysis (dose-response analysis, no lag time).
      We found increasing risk of lung cancer with increasing cumulative exposure to
      silica, with heterogeneity across studies however. Posthoc analyses identified a
      set of seven more homogeneous studies. Their meta-analysis resulted in a dose
      response curve that was not different from that obtained in the main analysis.
      CONCLUSION: Silica is a lung carcinogen. This increased risk is particularly
      apparent when the cumulative exposure to silica is well beyond that resulting
      from exposure to the recommended limit concentration for a prolonged period of
      time.

PMID- 19184476
TI  - Quantitative variation of LINE-1 sequences in five species and three subspecies
      of the subgenus Mus and in five Robertsonian races of Mus musculus domesticus.
AB  - The quantitative variation of a conserved region of the LINE-1 ORF2 sequence was
      determined in eight species and subspecies of the subgenus Mus (M. m. domesticus,
      M. m. musculus, M. m. castaneus, M. spicilegus, M. spretus, M. cervicolor, M.
      cookii, M. caroli) and five Robertsonian races of M. m. domesticus. No
      differences in LINE-1 ORF2 content were found between all acrocentric or
      Robertsonian chromosome races, whereas the quantitative variation of the LINE-1
      ORF2 sequences detected among the eight taxa partly matches with the clades into
      which the subgenus is divided. An accumulation of LINE-1 ORF2 elements likely
      occurred during the evolution of the subgenus. Within the Asiatic clade, M.
      cervicolor, cookii, and caroli show a low quantity of LINE-1 sequences, also
      detected within the Palearctic clade in M. m. castaneus and M. spretus,
      representing perhaps the ancestral condition within the subgenus. On the other
      hand, M. m. domesticus, M. m. musculus and M. spicilegus showed a high content of
      LINE-1 ORF2 sequences. Comparison between the chromosomal hybridization pattern
      of M. m. domesticus, which possesses the highest content, and M. spicilegus did
      not show any difference in the LINE-1 ORF2 distribution, suggesting that the
      quantitative variation of this sequence family did not involve chromosome
      restructuring or a preferential chromosome accumulation, during the evolution of
      M. m. domesticus.

PMID- 19184477
TI  - Intermittent hypoxia is an angiogenic inducer for endothelial cells: role of HIF
      1.
AB  - The presence of hypoxia in tumor and its role in promoting angiogenesis are well
      established. Recently, in addition to chronic hypoxia, cycling or intermittent
      hypoxia has also been demonstrated. However, its role in inducing new blood
      vessel formation is less clear. This work is aimed to investigate whether
      intermittent hypoxia can induce a pro-angiogenic phenotype in endothelial cells,
      in vitro. We studied changes in the expression of genes involved in inflammation
      and angiogenesis under intermittent and chronic hypoxia. We evidenced genes
      specifically expressed under intermittent hypoxia, suggesting different cell
      responses induced by intermittent versus chronic hypoxia. An increase in the
      expression of pro-angiogenic and pro-inflammatory genes under intermittent
      hypoxia, translating a pro-angiogenic effect of intermittent hypoxia was
      detected. In parallel, we investigated the activity of three transcription
      factors known to be activated either under hypoxia or by reoxygenation: HIF-1,
      Nrf2, and NF-kappaB. HIF-1alpha stabilization and an increase in HIF-1
      transcriptional activity were evidenced under intermittent hypoxia. On the other
      hand, NRF2 and NF-kappaB transcription factors were not activated. Finally, an
      increase in endothelial cell migration and in tubulogenesis in the course of
      hypoxia-reoxygenation cycles was evidenced, which was inhibited by HIF-1alpha
      siRNA. All together, these results demonstrate a clear pro-angiogenic effect of
      intermittent hypoxia.

PMID- 19184478
TI  - Effects of crude oil residuals on soil chemical properties in oil sites, Momoge
      Wetland, China.
AB  - Crude oil exploration and production has been the largest anthropogenic factor
      contributing to the degradation of Momoge Wetland, China. To study the effects of
      crude oil on wetland soils, we examined the total petroleum hydrocarbon (TPH),
      total organic carbon (TOC), total nitrogen (TN), and total phosphorus (TP), as
      well as pH and electricity conductivity (EC) from oil sites and uncontaminated
      areas in the Momoge Wetland. All contaminated areas had significantly higher (p <
      0.05) contents of TPH and TOC, but significantly lower (p < 0.05) TN contents
      than those of the uncontaminated areas. Contaminated sites also exhibited
      significantly higher (p < 0.05) pH values, C/N and C/P ratios. For TP contents
      and EC, no significant changes were detected. The level of soil contamination and
      impact of oil residuals on soil quality greatly depended on the length of time
      the oil well was in production. Oil residuals had caused some major changes in
      the soils' chemical properties in the Momoge Wetland.

PMID- 19184479
TI  - European bee-eater (Merops apiaster) populations under arsenic and metal stress:
      evaluation of exposure at a mining site.
AB  - Two populations of the European bee-eater were studied, one living at a reference
      site and the other at a metal mining site. The concentration of arsenic and 11
      metals (Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, and Zn) was measured in feathers
      and regurgitated pellets collected at both sites. Cadmium, chromium, mercury,
      nickel, and lead were at least twofold higher in feathers of birds from the
      contaminated site than in the reference site, suggesting that this population was
      exposed to higher metal levels. Similarly, levels of aluminum, arsenic, cadmium,
      cobalt, chromium, iron, and lead were also at least twofold higher in pellets
      from the contaminated area. The obtained results suggested that the impacted
      population of Merops apiaster is at risk due to the exposure to some metals.

PMID- 19184480
TI  - Identification of ozone stress in Indian rice through foliar injury and
      differential protein profile.
AB  - The present study showed a possibility to use phenotypic and proteomic responses
      in rice plants as an in vivo biomarker to detect higher concentrations of ambient
      ozone (O(3)). The investigation was done on two cultivars of Indian rice using
      open top chambers ventilated with charcoal filtered air, ambient air, ambient air
      with 10 ppb O(3) exposure and ambient air with 20 ppb O(3) exposure at a rural
      site of Varanasi, India. Results showed that the magnitude of O(3) induced
      specific type of foliar injury directly depends on the duration and concentration
      of O(3) exposure. Even the internal protein profile of injured and normal leaf
      demonstrated a differential expression, which directly indicates towards the
      molecular basis of plant's response against O(3).

PMID- 19184481
TI  - Water quality assessment near an industrial site of Damodar River, India.
AB  - An assessment on the water quality parameters coliform including the bacterial
      abundance from a point source of river Damodar (24 degrees 26(') N and 86 degrees
      53(') E), West Bengal, India was carried out during the period of 2004-2007. The
      site received mining and industrial effluents from the collieries and industries.
      The water samples collected on a monthly basis revealed the presence of the
      coliform bacteria Escherichia coli and Streptococcus sp., between 2,600 and
      20,000 colony-forming unit/100 ml throughout the study period with peak abundance
      during the months of September to December, the post-monsoon period. The relative
      abundance of the two bacterial species was found to be y(E. coli) = 1.41x
      (Streptococcus) - 8.07 and were positively correlated (r = + 0.868, df = 34).
      Principal component analysis revealed three factors to clarify for the observed
      variance of the environmental variables. The mean values of the physicochemical
      parameters of the river water at the sampling sites were consistently higher than
      the levels specified by WHO and other regulatory bodies and qualify as polluted
      water. The presence of the coliform bacteria in these water samples warrants for
      proper measure to reduce the pollution at the point source and proper remediation
      strategies to combat contamination in the domestic water usage from river Damodar
      from this site and downstream.

PMID- 19184482
TI  - Bisphenol A occurred in Kao-Pin River and its tributaries in Taiwan.
AB  - Bisphenol A (BPA), one of the endocrine-disrupting chemicals, was detected in
      water collected from Kao-Pin River and its tributaries. Results indicated that
      59% of the water samples contained BPA. Concentrations ranged from less than the
      limit of detection (LOD, 0.037) to 4.23 microg/L. The mean concentrations were
      0.16, 0.20, 1.02, 1.30, and 0.30 microg/L for sampling sites S1, S2, S3, S4, and
      S5, respectively. Concentrations were not significantly different between high
      and low-flow periods in sites S2, S3, and S4. In site S1, concentrations in the
      high-flow period were significantly greater than during the lower flow period,
      and in site S5, BPA concentration in the low-flow period was significantly
      greater than in the high-flow period. The BPA mass flow rate in site S5 was
      greater in the high-flow period than in the low-flow period.

PMID- 19184483
TI  - Wells sanitary inspection and water quality monitoring in Ban Nam Khem (Thailand)
      30 months after 2004 Indian Ocean tsunami.
AB  - This paper reports the results of a study conducted in Ban Nam Khem village, the
      most hit in Thailand by 2004 Indian Ocean tsunami, aimed to evaluate either the
      actual state and operation of numerous domestic wells present in the village or
      the quality of drawn groundwater. Data show that most critical chemical-physical
      parameters are turbidity, total organic carbon and iron, whereas conductivity has
      greatly decreased in comparison with the February 2005 monitoring campaign.
      Furthermore, a high faecal contamination related to both constructive and
      operational deficiencies was detected in most monitored wells; therefore,
      measures aimed at improving habits in well operation and favouring water domestic
      treatment are necessary.

PMID- 19184484
TI  - Behaviour of selected endocrine-disrupting chemicals in three sewage treatment
      plants of Beijing, China.
AB  - Occurrence and fate of eight kinds of selected endocrine-disrupting compounds
      (EDCs) in three sewage treatment plants (STPs) of Beijing, China was
      investigated. These EDCs, composed of 4-octylphenol (4-OP), 4-n-nonylphenol (4-n
      NP), bisphenol A (BPA), estrone (E1), 17alpha-estradiol (17alpha-E2), 17beta
      estradiol (E2), estriol (E3) and 17alpha-ethinylestradiol (EE2), in every step of
      STPs, were simultaneously analysed by gas chromatography/mass spectrometry after
      derivatisation. All the EDCs were detected in the influents of three STPs, and
      BPA was the most abundant compound. The concentrations of EDCs ranged from 36.6
      ng/l of 17alpha-E2 (STP C) to 1342.3 ng/l of BPA (STP B) in the influent sewages
      and from below limits of detection of E2 and E3 (STP C) to 142.5 ng/l of E1 (STP
      B) in the effluent sewages. The STPs could not remove alkylphenols effectively
      from the aqueous phase with less than 40% reduction. BPA decreased over 90%, and
      steroid estrogens achieved considerable reductions from 64.8% of E2 to 94.9% of
      E3. Generally, biological treatment was more effective in removing alkylphenols,
      BPA and natural estrogens from the aqueous phase than primary treatment. However,
      the synthetic estrogen, EE2, was mostly removed by the primary treatment with
      about 63.5% reduction. It is the first time that the concentration of 17alpha-E2
      in the sewage of China was reported in this paper. The compound might have a
      bearing with the waste effluents of dairy farms around urban area of Beijing.

PMID- 19184485
TI  - Heavy metals in bottom sediments of Lake Umbozero in Murmansk Region, Russia.
AB  - Sediment cores collected from different locations of Lake Umbozero were studied
      with respect to concentration and mobility of trace and heavy metals Co, Cu, Fe,
      Mn, Ni, Pb, U, and Zn. Lake Umbozero is the second largest lake in the Murmansk
      Region and subjected to contamination by air-borne emissions and river
      transportation from the nearby metallurgical and mining industries. Unlike its
      neighboring, more industry-prone Lake Imandra, Lake Umbozero is relatively
      unexplored with respect to its state of pollution. In our study, metal
      distribution in sediments was found to vary with respect to the cores, although
      in general the concentrations were at the same level throughout the lake
      indicating uniform horizontal distribution of metals. When compared to Lake
      Imandra, the concentrations of most of the metals studied were significantly
      lower and represented the levels in sediments measured in lakes of Kola Peninsula
      located further off from industrial pollutant sources. An exception was Pb the
      concentration of which was at the same level as in Lake Imandra, probably due to
      long-distance transport. Sediment layers were subjected to four-step sequential
      extraction procedure to reveal the metal distribution in soluble, exchangeable,
      acid-soluble, and residual fractions. Indicative of their potential higher
      lability, Mn, U, and Zn were generally found in exchangeable fraction; as also Mn
      and U extensively in the acid-soluble fraction.

PMID- 19184486
TI  - Fish diversity with relation to water quality of Bhadra River of Western Ghats
      (INDIA).
AB  - Water quality assessment and freshwater fish diversity of Bhadra river, Western
      Ghats, Karnataka was examined. River water was clear except at one station (BV
      Site) with rocky and sandy substrate. The mean water quality of study sites were
      as following, pH 6.98, air temperature 22.66 degrees C, water temperature 20.16
      degrees C, dissolved oxygen 8.74 mg/l, total hardness 27 mg/l, alkalinity 48 mg/l
      (as CaCO(3)), conductivity 135.5 mhos/cm, COD (15.16 mg/l), and BOD (3.78 mg/l),
      respectively. Altogether, 56 species of fish representing 31 genera and 15
      families were recorded. The Cyprinid family was dominant in the present study.
      Various diversity index packages have been used to assess the fish diversity.
      Fish diversity is also correlated with physicochemical variables.

PMID- 19184487
TI  - Parallel factor analysis of fluorescence EEM spectra to identify THM precursors
      in lake waters.
AB  - Dissolved organic matter (DOM) can react with chlorine and yield undesirable
      disinfection byproducts (DBPs), e.g., trihalomethanes (THMs). Numerous studies
      have demonstrated that various DOM constituents have DBP formation potentials. We
      explored in this study the use of fluorescence excitation-emission (EEM)
      spectroscopy to identify THM precursors in 55 lakes in Missouri, USA. EEMs of the
      lake waters were decomposed into five factors of different origins through
      parallel factor analysis. The correlations between the component scores of the
      factors and THM formation potentials reveal that factors 1 and 2 are likely THM
      precursors and provided better surrogates than SUVA (dissolved organic carbon
      normalized UV254) for predicting DBP formation potential. Thus, monitoring the
      component scores of the DOM-origin factors would provide a practical tool to
      identify THM precursors and facilitate utilities to choose appropriate techniques
      for DBP mitigation and optimize the degree of water treatment.

PMID- 19184488
TI  - Effectiveness of wastewater management in rural areas of developing countries: a
      case of Al-Chouf Caza in Lebanon.
AB  - Alike many developing countries, Lebanon lacks a national wastewater management
      strategy that can effectively protect public health and environmental quality.
      This has led the local communities and municipalities to plan and implement their
      own arrangements for wastewater treatment systems. However, most municipalities
      still lack the human and financial resources, management capabilities, and
      environmental awareness necessary to implement wastewater management in an
      environmentally sound manner. As such, the effectiveness of these systems,
      particularly with regard to the quality of the treated effluent, warrants
      evaluation. Accordingly, a performance evaluation of the treatment/disposal
      systems, taking three villages in Al-Chouf Caza in Lebanon as a case study, was
      carried out. The conducted field work, visual assessment, and laboratory analyses
      of effluent discharges revealed that the existing systems for wastewater
      treatment in the three villages are either not properly functioning or
      operational but ineffective and, consequently, hardly achieve any treatment
      higher than primary. Although developing countries are being encouraged to
      implement wastewater treatment systems with the promise of financial aid from
      developed nations, it is important that local conditions are considered carefully
      to make full use of any aid. It is very crucial to take into account the economic
      status of the community and the municipality in question. There is no point in
      adopting the most advanced technology for wastewater treatment if there is no
      mechanism to ensure maximum efficiency.

PMID- 19184489
TI  - Evaluating the urban climate of a typically tropical city of northeastern Brazil.
AB  - This study attempted to assess a bioclimate index and the occurrence of an urban
      heat island in the city of Campina Grande, northeastern Brazil, using data taken
      from mobile measurements and Automatic Weather Stations (AWS). The climate data
      were obtained during two representative months, one for the dry season (November
      2005) and one for the rainy season (June 2006) at seven points in an urban area.
      Ten-minute air temperatures recorded by an AWS installed in urban areas were
      compared to those from a similar station located in a suburban area to assess the
      urban heat island (UHI). The data were collected using a 23X data logger
      (Campbell Scientific, Inc.) programmed for collecting data every second. The
      thermal discomfort level was analyzed by Thom's discomfort index (DI), and an
      analysis of variance was applied for assessing if there was any statistically
      significant difference at the 1% and 5% significance level of thermal comfort
      among points. Mann-Kendall statistical test was used for identifying possibly
      significant trends in a time series for air temperature, relative humidity, and
      class A pan evaporation for the city of Campina Grande. The present study found
      UHI intensities of 1.48 degrees C and -0.7 degrees C for the months taken as
      representative of the dry and rainy seasons, respectively. Summer in the city has
      partially comfortable conditions while the winter is fully comfortable. There are
      significant changes in DI hourly values between seasons. Only during the rainy
      season did all points of the city have a comfortable condition until 8:19 h, at
      which time they become partially comfortable for the rest of the day. Results
      indicated that there was a 1.5 degrees C increase in air temperature and a 7.2%
      reduction in relative humidity throughout the analyzed time series. The DI also
      showed a statistically significant increasing trend (Mann-Kendall test, p < 0.01)
      for the dry and rainy seasons and annual period of approximately 1 degree C in
      the last 41 years in the city of Campina Grande.

PMID- 19184490
TI  - Evaluating forest fragmentation and its tree community composition in the
      tropical rain forest of Southern Western Ghats (India) from 1973 to 2004.
AB  - A majority of the research on forest fragmentation is primarily focused on animal
      groups rather than on tree communities because of the complex structural and
      functional behavior of the latter. In this study, we show that forest
      fragmentation provokes surprisingly rapid and profound alterations in tropical
      tree community. We examine forest fragments in the tropical region using high
      resolution satellite imagery taken between 1973 and 2004 in the Southern Western
      Ghats (India) in relation to landscape patterns and phytosociological datasets.
      We have distinguished fragmentation in six categories--interior, perforated,
      edge, transitional, patch, and undetermined--around each forested pixel.
      Furthermore, we have characterized each of the fragment class in the evergreen
      and semi-evergreen forest in terms of its species composition and richness, its
      species similarity and abundance, and its regeneration status. Different
      landscape metrics have been used to infer patterns of land-use changes.
      Contiguous patches of >1,000 ha covered 90% of evergreen forest in 1973 with less
      porosity and minimal plantation and anthropogenic pressures; whereas in 2004, the
      area had 67% forest coverage and a high level of porosity, possibly due to
      Ochlandra spread and increased plantations which resulted in the loss of such
      contiguous patches. Results highlight the importance of landscape metrics in
      monitoring land-cover change over time. Our main conclusion was to develop an
      approach, which combines information regarding land cover, degree of
      fragmentation, and phytosociological inputs, to conserve and prioritize tropical
      ecosystems.

PMID- 19184491
TI  - Development of a low-cost system for measuring conditional time-averaged
      gradients of SO2 and NH3.
AB  - A conditional time-averaged gradient (COTAG) system has been developed to provide
      direct long-term (weekly to monthly) average flux gradient measurements for a
      range of trace gases, between land and atmosphere. Over daily periods,
      atmospheric conditions can range from high stability, where the vertical
      gradients of ambient concentration are enhanced due to very small diffusivity, to
      highly unstable conditions, in which concentration gradients are small due to the
      intense turbulent activity of the surface layer. The large vertical gradients
      generated by high stability would bias the estimate of the actual flux: to avoid
      this, the COTAG system samples conditionally, within a carefully refined range of
      stability. A comparison with a continuous flux gradient system suggested that the
      removal of stable conditions from the sampling period does not substantially
      modify the evaluation of the long-term fluxes.

PMID- 19184492
TI  - Occurrence of organochlorine pesticide residues in green mussel (Perna viridis
      L.) and water from Ennore creek, Chennai, India.
AB  - Green mussel (Perna viridis) and water samples were collected from Ennore creek,
      Chennai by seasonal sampling and analyzed for organochlorine pesticide residues
      (OCPs) like dichloro-diphenyl-trichloroethane (DDT) and its metabolites, isomers
      of hexachlorocyclohexane (HCH) and endosulfan. These residues were analyzed by
      using gas chromatograph (GC) with microECD. In the present study, mussel samples
      showed very low concentrations of OCPs in the statistical order of DDT (5.83 ng
      g(-1) wet tissue)>endosulfan (2.84 ng g(-1) wet tissue)>HCH (2.34 ng g(-1) wet
      tissue). Concentrations of OCPs in water samples were in the statistical order of
      endosulfan (29.21 ng L(-1))>HCH (17.14 ng L(-1))>DDT (14.63 ng L(-1)). To our
      knowledge, this is the first report on the seasonal variation of OCPs and
      especially the quantification of endosulfan in Ennore Creek. The present study
      recommends that continuous monitoring in Ennore creek is necessary to assess
      possible impact on human health.

PMID- 19184494
TI  - Indifference curves as a tool for environment impact assessment.
AB  - Use of indifference curves, defined as functionality between development index
      and pollution load to evaluate environmental impact, is proposed. Existing
      Battelle environmental evaluation methodology is subjective in its approach. The
      use of indifference curves lends a more objective approach to environment
      assessment methodology. The extent of environmental damage we are prepared to
      accept, for a development, can be explained by Willingness to Pay and Willingness
      to Accept approach. The application of proposed approach has been demonstrated
      taking an example of Power plant set up in forest area. The curves clearly show
      that cost of EMP considering mitigation of ecological damage is higher than the
      EMP mitigating impacts of air and water pollution only. The example stresses the
      need for willingness to accept along with willingness to pay.

PMID- 19184493
TI  - Chromium speciation in groundwater of a tannery polluted area of Chennai City,
      India.
AB  - Chromium speciation in groundwater of a tannery polluted area was investigated
      for the distribution of chromium species and the influence of redox couples such
      as Fe(III)/Fe(II) and Mn(IV)/Mn(II). Speciation analysis was carried out by
      ammonium pyrolidinedithiocarbamate (APDC)-methylisobutylketone (MIBK) procedure.
      The groundwater samples were analyzed for Cr(III), Cr(VI), and Cr(III)-organic
      complexes. The APDC could not extract the Cr(III)-organic complexes, but HNO3
      digestion of the groundwater samples released the Cr(III)-organic complexes. The
      groundwater of the area is relatively oxidizing with redox potential (Eh) and
      dissolved oxygen (DO) ranged between 65 and 299 mV and 0.25 and 4.65 mg L(-1),
      respectively. The Fe(II) reduction of Cr(VI) was observed in some wells, but
      several wells that had Fe(II)/Cr(VI) concentrations more than the stoichiometric
      ratio (3:1) of the reduction reaction also had appreciable concentration of
      Cr(VI). This could partly be due to the oxidation of Fe(II) to Fe(III) by DO. It
      appears that the occurrence of Mn more than the Fe(II) concentration was also
      responsible for the presence of Cr(VI). Other reasons could be the Fe(II)
      complexation by organic ligands and the loss of reducing capacity of Fe(II) due
      to aquifer materials, but could not be established in this study.

PMID- 19184495
TI  - Two-dimensional finite elements model for boron management in agroforestry sites.
AB  - Agroforesty systems, which are recommended as a management option to lower the
      shallow groundwater level and to reuse saline subsurface drainage waters from the
      tile-drained croplands in the drainage-impacted areas of Jan Joaquin Valley of
      California, have resulted in excessive boron buildup in the soil root zone. To
      assess the efficacy of the long-term impacts of soil boron buildup in agroforesty
      systems, a mathematical model was developed to simulate non-conservative boron
      transport. The developed dynamic two-dimensional finite element model simulates
      water flow and boron transport in saturated-unsaturated soil system, including
      boron sorption and boron uptake by root-water extraction processes. The
      simulation of two different observed field data sets by the developed model is
      satisfactory, with mean absolute error of 1.5 mg/L and relative error of 6.5%.
      Application of the model to three different soils shows that boron adsorption is
      higher in silt loam soil than that in sandy loam and clay loam soils. This result
      agrees with the laboratory experimental observations. The results of the
      sensitivity analysis indicate that boron uptake by root-water extraction process
      influences the boron concentration distribution along the root zone. Also,
      absorption coefficient and maximum adsorptive capacity of a soil for boron are
      found to be sensitive parameters.

PMID- 19184496
TI  - Air quality assessment in Southern Kuwait using diffusive passive samplers.
AB  - Measurements of fortnightly average concentrations of NO, NO2, SO2, H2S, NH3, and
      volatile organic compounds (VOCs) (aromatics=benzene, toluene, o-xylene, m+p
      xylene, ethyl benzene; non-aromatics=nonane and octane) were carried out in the
      period from 26/10/05 to 24/11/05 at 20 points in the southern part of Kuwait as
      part of a baseline environmental impact assessment study requested by Kuwait
      National Petroleum Company. Two waves of triplicate diffusive passive samplers
      were used. A high volume air sampler was used to measure PM10 too. During the
      sampling period, the wind was observed to be mainly from the west and northwest
      with an average of 4.28 m/s. The consistency of the results allowed the
      production of spatial distribution maps of the pollutants measured and
      consequently the comparison between levels of air pollution at different
      locations. A comparison between the measured concentrations and the applicable
      air quality standards promulgated by Kuwait Environment Public Authority (KEPA)
      showed that those compounds had low concentrations compared to both industrial
      and residential KEPA standards. For other compounds which are not covered by KEPA
      standards, the results were compared with relevant limits of US Environment
      Protect Agency (USEPA) and US Department of Labor, Occupational Safety and Health
      Administration. The comparison showed that the measured compounds had low
      concentrations compared to the existing standards and, accordingly, no violation
      of air quality standards is reported.

PMID- 19184497
TI  - Blended learning positively affects students' satisfaction and the role of the
      tutor in the problem-based learning process: results of a mixed-method
      evaluation.
AB  - Problem-based learning (PBL) is an established didactic approach in medical
      education worldwide. The impact of PBL depends on the tutors' quality and the
      students' motivation. To enhance students' motivation and satisfaction and to
      overcome the problems with the changing quality of tutors, online learning and
      face-to-face classes were systematically combined resulting in a blended learning
      scenario (blended problem-based learning--bPBL). The study aims at determining
      whether bPBL increases the students' motivation and supports the learning process
      with respect to the students' cooperation, their orientation, and more reliable
      tutoring. The blended PBL was developed in a cooperation of students and
      teachers. The well-established Seven Jump-scheme of PBL was carefully
      complemented by eLearning modules. On the first training day of bPBL the students
      start to work together with the online program, but without a tutor, on the final
      training day the tutor participates in the meeting for additional help and
      feedback. The program was evaluated by a mixed-method study. The traditional PBL
      course was compared with the blended PBL by means of qualitative and quantitative
      questionnaires, standardized group interviews, and students' test results. In
      addition log-files were analyzed. A total of 185 third-year students and 14
      tutors took part in the study. Motivation, subjective learning gains and
      satisfaction achieved significantly higher ratings by the bPBL students compared
      with the students learning by traditional PBL. The tutors' opinion and the test
      results showed no differences between the groups. Working with the web-based
      learning environment was assessed as very good by the students. According to the
      log-file analysis, the web-based learning module was frequently used and improved
      the cooperation during the self-directed learning.

PMID- 19184498
TI  - Exposure of medical students to pharmaceutical marketing in primary care
      settings: frequent and influential.
AB  - It is known that interaction between pharmaceutical companies and medical
      professionals may lead to corruption of professional values, irrational use of
      medicine, and negative effects on the patient-physician relationship. Medical
      students frequently interact with pharmaceutical company representatives and
      increasingly accept their gifts. Considering the move toward early clinical
      encounters and community-based education, which expose students early to
      pharmaceutical representatives, the influence of those gifts is becoming a matter
      of concern. This study examines the frequency and influence of student exposure
      to drug marketing in primary care settings, as well as student perceptions of
      physician-pharmaceutical company relationships. This was a two-phase study
      consisting of qualitative research followed by a cross-sectional survey. Clinical
      experience logbooks of 280 second-year students in one school were analysed, and
      the themes that emerged were used to develop a survey that was administered to
      308 third-year students from two medical schools. Survey results showed a 91.2%
      exposure to any type of marketing, and 56.8% of students were exposed to all
      classes of marketing methods studied. Deliberate targeting of students by
      pharmaceutical representatives, in particular, was correlated with being less
      sensitive to the negative effects of and having positive opinions about
      interactions with pharmaceutical companies. The vast majority of students are
      exposed to drug marketing in primary care settings, and may become more
      vulnerable to that strategy. Considering that medical students are vulnerable and
      are targeted deliberately by pharmaceutical companies, interventions aimed at
      developing skills in the rational use of medicines and in strategies for coping
      with drug marketing should be devised.

PMID- 19184499
TI  - Fragment-based QSAR: perspectives in drug design.
AB  - Drug design is a process driven by innovation and technological breakthroughs
      involving a combination of advanced experimental and computational methods. A
      broad variety of medicinal chemistry approaches can be used for the
      identification of hits, generation of leads, as well as to accelerate the
      optimization of leads into drug candidates. Quantitative structure-activity
      relationship (QSAR) methods are among the most important strategies that can be
      applied for the successful design of small molecule modulators having clinical
      utility. Hologram QSAR (HQSAR) is a modern 2D fragment-based QSAR method that
      employs specialized molecular fingerprints. HQSAR can be applied to large data
      sets of compounds, as well as traditional-size sets, being a versatile tool in
      drug design. The HQSAR approach has evolved from a classical use in the
      generation of standard QSAR models for data correlation and prediction into
      advanced drug design tools for virtual screening and pharmacokinetic property
      prediction. This paper provides a brief perspective on the evolution and current
      status of HQSAR, highlighting present challenges and new opportunities in drug
      design.

PMID- 19184500
TI  - Reactions of 3-benzoyl-7-dimethylamino-4-hydroxycoumarin and their potential
      applications in solution- and solid-phase synthesis.
AB  - 3-Benzoyl-7-dimethylamino-4-hydroxycoumarin was synthesized and its UV-vis
      spectra in various mixtures of MeOH and CH(2)Cl(2) were measured. The diketone
      lactone exists mainly in the exocyclic-enol form in protic solvents and the
      endocyclic-enol form in nonpolar solvents. Acetylation, amination and methylation
      products of the diketone lactone were characterized by X-ray crystallography. The
      results indicated that acetylation of coumarin-based diketone lactones occurs
      exclusively at the 4-hydroxy group, but that amination takes place specifically
      at the C-3 carbonyl group. Among the prepared compounds, amination products were
      found to exhibit photochromic property and colorimetric ion-sensing ability, and
      methylation product has the potential to function as a primary amine protection
      group.

PMID- 19184501
TI  - Goat RSPO1 over-expression rescues sex-reversal in Rspo1-knockout XX mice but
      does not perturb testis differentiation in XY or sex-reversed XX mice.
AB  - RSPO1 is a newly discovered gene involved in sex differentiation. Two goat BAC
      clones encompassing the RSPO1 gene (gRSPO1) were injected into mouse oocytes and
      several transgenic lines derived. Both clones induced gRSPO1 over-expression in
      various tissues, including male and female gonads, with no obvious phenotype and
      normal sex-ratios. Introgression of the gRSPO1 transgene into a mouse RSPO1
      knockout genotype resulted in the rescue of the fertility and the disappearance
      of the masculinized gonadic features of the females, demonstrating the
      functionality of the goat protein in a mouse context. On the contrary, over
      expression of gRSPO1 within a mSRY or a gSRY-XX genotypes did not interfere with
      the SRY-induced male phenotype.

PMID- 19184502
TI  - Extensive homologous recombination between introduced and native regulatory
      plastid DNA elements in transplastomic plants.
AB  - Homologous recombination within plastids directs plastid genome transformation
      for foreign gene expression and study of plastid gene function. Though transgenes
      are generally efficiently targeted to their desired insertion site, unintended
      homologous recombination events have been observed during plastid transformation.
      To understand the nature and abundance of these recombination events, we analyzed
      transplastomic tobacco lines derived from three different plastid transformation
      vectors utilizing two different loci for foreign gene insertion. Two unintended
      recombinant plastid DNA species were formed from each regulatory plastid DNA
      element included in the transformation vector. Some of these recombinant DNA
      species accumulated to as much as 10-60% of the amount of the desired integrated
      transgenic sequence in T0 plants. Some of the recombinant DNA species undergo
      further, "secondary" recombination events, resulting in an even greater number of
      recombinant plastid DNA species. The abundance of novel recombinant DNA species
      was higher in T0 plants than in T1 progeny, indicating that the ancillary
      recombination events described here may have the greatest impact during selection
      and regeneration of transformants. A line of transplastomic tobacco was
      identified containing an antibiotic resistance gene unlinked from the intended
      transgene insertion as a result of an unintended recombination event, indicating
      that the homologous recombination events described here may hinder efficient
      recovery of plastid transformants containing the desired transgene.

PMID- 19184505
TI  - Studies on the Eimeria of goats at Magadu Dairy Farm SUA, Morogoro, Tanzania.

PMID- 19184503
TI  - Hemizygous minipigs produced by random gene insertion and handmade cloning
      express the Alzheimer's disease-causing dominant mutation APPsw.
AB  - In an effort to develop a porcine model of Alzheimer's disease we used handmade
      cloning to produce seven transgenic Gottingen minipigs. The donor fibroblasts had
      been stably transfected with a plasmid cassette containing, as transgene, the
      cDNA of the neuronal variant of the human amyloid precursor protein gene with the
      Swedish mutation preceded by beta-globin sequences to induce splicing and a human
      PDGF beta promoter fragment to drive transcription. Transgene insertion had
      occurred only at the GLIS3 locus where a single complete copy of the transgene
      was identified in intronic sequences in opposite direction. Similar and robust
      levels of the transgene transcript were detected in skin biopsies from all
      piglets and the sequence of full-length transcript was verified. Consistent with
      PDGF beta promoter function, high levels of transgene expression, including high
      level of the corresponding protein, was observed in brain tissue and not in heart
      or liver tissues. A rough estimate predicts that accumulation of the A beta
      peptide in the brain may develop at the age of 1-2 years.

PMID- 19184504
TI  - Tissue specific expression of potent insecticidal, Allium sativum leaf agglutinin
      (ASAL) in important pulse crop, chickpea (Cicer arietinum L.) to resist the
      phloem feeding Aphis craccivora.
AB  - The phloem sap-sucking hemipteran insect, Aphis craccivora, commonly known as
      cowpea aphid, cause major yield loss of important food legume crop chickpea.
      Among different plant lectins Allium sativum leaf agglutinin (ASAL), a mannose
      binding lectin was found to be potent antifeedant for sap sucking insect A.
      craccivora. Present study describes expression of ASAL in chickpea through
      Agrobacterium-mediated transformation of "single cotyledon with half embryo"
      explant. ASAL was expressed under the control of CaMV35S promoter for
      constitutive expression and phloem specific rolC promoter for specifically
      targeting the toxin at feeding site, using pCAMBIA2301 vector containing plant
      selection marker nptII. Southern blot analysis demonstrated the integration and
      copy number of chimeric ASAL gene in chickpea and its inheritance in T(1) and
      T(2) progeny plants. Expression of ASAL in T(0) and T(1) plants was confirmed
      through northern and western blot analysis. The segregation pattern of ASAL
      transgene was observed in T(1) progenies, which followed the 3:1 Mendelian ratio.
      Enzyme linked immunosorbant assay (ELISA) determined the level of ASAL expression
      in different transgenic lines in the range of 0.08-0.38% of total soluble
      protein. The phloem tissue specific expression of ASAL gene driven by rolC
      promoter has been monitored by immunolocalization analysis of mature stem
      sections. Survival and fecundity of A. craccivora decreased to 11-26% and 22-42%,
      respectively when in planta bioassay conducted on T(1) plants compared to
      untransformed control plant which showed 85% survival. Thus, through unique
      approach of phloem specific expression of novel insecticidal lectin (ASAL), aphid
      resistance has been successfully achieved in chickpea.

PMID- 19184506
TI  - Prevalence and intensity of Oestrus ovis in sheep of Shiraz, southern Iran.
AB  - Two thousand and two heads obtained from slaughtered sheep at the Fars abattoirs
      (Shiraz, Southern Iran) between April 2006 and April 2007 were examined for the
      presence of Oestrus ovis larvae. Of the total heads, 995 (49.7%) were infested
      with O. ovis larvae. O. ovis larvae were observed in both sexes and all age
      groups in each season of the year. A total of 6264 larvae were collected. The
      overall larval intensity for the infested sheep was 6.3, with 3.9 in spring, 5.3
      in summer, 5.9 in autumn and 7.8 in winter. Prevalence ranged from 23.3% in
      spring to 80% in winter. Increased infestation was observed in older animals.

PMID- 19184507
TI  - A retrospective survey of hydatidosis in livestock in Arusha, Tanzania, based on
      abattoir data during 2005-2007.
AB  - A 3-year (2005-2007) retrospective study was carried out to investigate the
      occurrence of cystic echinococcosis (CE) in cattle and shoats (sheep and goats)
      slaughtered at Arusha municipal abattoir, Tanzania. A total of 115,186 cattle and
      99,401 shoats were slaughtered. Cattle liver, lungs, spleen and heart
      condemnation rate was 16.35%, 13.04%, 2.09% and 3.06% respectively while 17.63%,
      7.63%, 0.38% and 0.04% of shoats' liver, lungs, spleen and heart respectively
      were condemned. A highly significant (p < 0.001) cystic echinococcosis (CE)
      infection rate was recorded in shoats (6.02%) than in cattle (4.2%) probably
      because of differences in grazing patterns. Cattle lungs were more affected by CE
      (22.5%) than liver (19.7%) while shoats liver were found to be more affected
      (21%) than the lungs (19.3). A significant (p < 0.001) higher CE infection rate
      was observed in cattle spleen (15.5%) than shoats (9.7%). There was no
      significant (p > 0.05) difference between condemnation rates due to hydatidosis
      during rain and dry seasons probably because of chronicity of the disease. The
      study have established that CE is prevalent in animals slaughtered at Arusha
      abattoir and causes higher condemnation rates of edible offals. This merit for
      more extensive epidemiological investigations to better determine the prevalence,
      economic impact and public health importance of the disease in the region.

PMID- 19184508
TI  - Ocurrence of Philophthalmus gralli (Trematoda: Philophthalmidae) in farmed
      ostriches in Brazil.
AB  - This paper reports the occurrence of parasitism by the Oriental eye-fluke,
      Philophthalmus gralli in ostriches reared in a commercial flock from the State of
      Minas Gerais State, Southeastern Brazil. The two affected birds presented
      lacrimation, inflammatory reaction and loss of body condition. After physical
      examination the birds revealed, 17 and 15 trematodes each, only in the right
      eyes. The economic impact of this parasite on Brazilian ostrich industry is still
      undetermined, requiring further studies.

PMID- 19184509
TI  - Is efficacy of repeated intradetrusor botulinum toxin type A (Dysport) injections
      dose dependent? Clinical and urodynamic results after four injections in patients
      with drug-resistant neurogenic detrusor overactivity.
AB  - OBJECTIVE: To assess the effects of two different doses of botulinum toxin A
      (Dysport: 500 and 1,000 IU) injected repeatedly into the bladder for the
      treatment of neurogenic detrusor overactivity (NDO) in terms of safety,
      durability, and improvement of continence status and urodynamic parameters.
      PATIENTS AND METHODS: In this study we analyzed the effects of successive doses
      of 500 or 1,000 IU of Dysport, endoscopically injected into the detrusor muscle.
      Clinical, urodynamic, and satisfaction assessments were performed at baseline and
      6 weeks after each injection. The results of injections and corresponding follow
      ups were analyzed and compared with baseline. RESULTS: Twenty-two patients (13
      men and 9 women) with repeated four injections were included, of whom 12 (55%)
      with mean age 35.7 years (range 16-52 years) received 500 IU of BTX-A and 10
      (45%) with mean age 33.8 years (range 18-50 years) received 1,000 IU in each
      treatment. No statistically significant differences were found in efficacy
      duration with the two Dysport doses (500 IU: 7.7 months, 1,000 IU: 8.5 months; P
      > 0.05). Maximum cystometric capacity (MCC), reflex volume (RV), and bladder
      compliance (BC), and patient satisfaction improved significantly after each
      treatment compared with baseline values and there were no statistically
      significant differences after each retreatment for the two treatment groups (P >
      0.05). CONCLUSIONS: After repeated injections the effect of BTX-A remained
      constant. The cause of repeat treatment is relapse of overactive bladder
      symptoms. Results with the 500 and 1,000 IU doses were interesting and
      approximately equivalent in terms of duration and efficacy, with better but not
      significant results when 1,000 IU was used. The optimum dose of Dysport for
      incontinence secondary to NDO is not yet defined; 1,000 IU probably has a
      nonsignificant longer effect than 500 IU but may expose the patient to major
      complications. Further studies evaluating the clinical efficacy of 750 IU of
      Dysport are necessary.

PMID- 19184511
TI  - Relation of stiffness parameter beta to carotid arteriosclerosis and silent
      cerebral infarction in patients on chronic hemodialysis.
AB  - OBJECTIVE: Aortic stiffness measured by pulse wave velocity (PWV) predicts all
      cause and cardiovascular mortality in hemodialysis (HD) patients. However, there
      is a lack of information on stiffness parameter beta, another index of arterial
      stiffness, in HD patients. The aim of the present study was to investigate the
      clinical usefulness of stiffness parameter beta in HD patients. MATERIALS AND
      METHOD: We compared the relation of stiffness parameter beta to carotid intima
      media thickness (IMT) and plaque score estimated by carotid ultrasound and
      investigated the relationship between stiffness parameter beta and silent
      cerebral infarction (SCI) in 64 HD patients. RESULTS: Stiffness parameter beta
      was positively correlated with mean IMT (r = 0.318, P = 0.0113) and plaque score
      (r = 0.672, P < 0.0001). Stepwise regression analysis revealed that pulse
      pressure and age were found to be independent determinants of stiffness parameter
      beta (partial correlation coefficients: beta = 0.501 and P < 0.0001 for pulse
      pressure, beta = 0.488 and P < 0.0001 for age). In addition, stiffness parameter
      beta in patients with SCI (12.2 +/- 3.9) was significantly higher than those (8.0
      +/- 2.4) in patients without SCI. However, there was no significant difference in
      mean IMT and plaque score in both groups. CONCLUSION: These results suggest that
      arteriosclerosis assessed by stiffness parameter beta is associated with
      atherosclerotic changes of carotid arteries and with the presence of SCI in HD
      patients.

PMID- 19184510
TI  - Sleep disorders and quality of life in renal transplant recipients.
AB  - Kidney transplantation provides the best outcome for patients with end-stage
      renal failure both in terms of morbidity and mortality and health-related quality
      of life (QoL). Health-related QoL has become recognized as an important outcome
      measure in patients with different chronic medical conditions, including chronic
      kidney disease (CKD). There are several factors in kidney-transplanted patients
      which have a negative impact on QoL in these patients. Sleep disorders, such as
      insomnia, sleep apnea syndrome (SAS), and restless legs syndrome (RLS), are
      common in kidney-transplanted patients and clearly belong to this group of
      factors, although there is only limited published data available about the
      association between sleep problems and QoL in this patient population. The
      prevalence of both insomnia and RLS is reduced in kidney-transplanted patients
      compared to dialysis patients, and it is similar to the prevalence observed in
      the general population. The prevalence of sleep apnea, however, is very high,
      around 30%. The association between the presence of these sleep disorders and
      impaired QoL has been relatively well documented in dialysis patients, but there
      is only scarce published information about this association in the kidney
      transplant population. In this paper, we will summarize data from the literature
      describing the impact of sleep problems, which are potentially treatable, on QoL
      in kidney-transplanted patients. We suggest that the appropriate diagnosis and
      management of sleep disorders may improve QoL in kidney-transplanted patients.

PMID- 19184512
TI  - Visfatin and endogenous secretory receptor for advanced glycation end-products in
      diabetic type 2 and non-diabetic patients undergoing intermittent hemodialysis.
AB  - BACKGROUND/AIMS: To examine plasma levels of visfatin and endogenous secretory
      receptor for advanced glycation end-products (esRAGE) in diabetic and non
      diabetic patients treated with intermittent hemodialysis (IHD), and to explore
      the possible associations between them, insulin resistance evaluated by
      homeostasis model assessment for insulin resistance (HOMA-IR), as well as
      selected biochemical and anthropometric parameters. METHODS: The study was
      carried out in 65 IHD patients. Type 2 diabetic patients (n = 28) were included
      into group I, non-diabetics (n = 37)-into group II. The reference group included
      25 healthy volunteers. RESULTS: There were no significant differences between
      group I and II in plasma level of visfatin and esRAGE. HOMA-IR was higher in
      group I than in group II. In both groups these parameters were higher than in
      healthy subjects. In group I, visfatin correlated with insulin concentration (r =
      0.428, P = 0.023), HOMA-IR with esRAGE (r = -0.374, P = 0.049). In group II,
      esRAGE correlated with waist-to-hip ratio (r = -0.343, P = 0.037), HOMA-IR with
      body mass index (r = 0.499, P = 0.001) and LDL cholesterol (r = -0.384, P =
      0.018). CONCLUSIONS: Serum concentrations of visfatin and esRAGE are increased in
      IHD patients. There is no difference in visfatin and esRAGE levels between
      diabetic and non-diabetic IHD patients. In diabetic IHD patients receiving
      insulin, lower esRAGE levels are associated with higher insulin resistance,
      whereas plasma visfatin level is positively related to plasma insulin
      concentration. Waist-to-height ratio is a significant determinant of plasma
      visfatin level and HOMA-IR. Insulin resistance seems to be a link between esRAGE
      and visfatin in IHD diabetics.

PMID- 19184513
TI  - Renal AA amyloidosis: survey of epidemiologic and laboratory data from one
      nephrology centre.
AB  - Renal amyloid involvement results, especially, from AL (primary) or AA
      (secondary) amyloidosis. The extent of amyloid tissue deposits in the kidneys and
      the clinical course of amyloidosis not only depend on the type of basic process
      but also reflect the time of diagnosis and the ability to affect the underlying
      disease. We analyzed laboratory and clinical data from patients with bioptically
      proven renal amyloidosis. Renal amyloidosis was found in 99 patients (4.65%) from
      an overall number of 2,128 renal biopsies (RB) performed in our department during
      a period of 11 years (from 1995 to 2006). AA amyloidosis was diagnosed in 46
      patients. Nephrotic syndrome was diagnosed in 27 patients (59%) with AA
      amyloidosis; all these patients had different degrees of proteinuria. Impaired
      renal function was discovered in 24 patients (52%); in three of these patients
      (6.5%) we had to start renal replacement therapy. Patients were treated with
      corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biological
      therapy in various regimens. Nine patients (19.5%) died during the one-year
      follow-up period; complications such as sepsis and cardiac failure were the
      leading causes of death. Median survival in the AA group was 54 months. Although
      for approximately half of patients different treatment regimens can lead to a
      partial remission or disease stabilization, the prognosis of patients with
      amyloidosis could be regarded as unsatisfactory.

PMID- 19184514
TI  - Langerhans' cell density and degree of keratinization in foreskins of Chinese
      preschool boys and adults.
AB  - BACKGROUND: Recent epidemiological studies have proposed that male circumcision
      reduces the relative risk of acquiring HIV-1. Here, we evaluated the density of
      Langerhans' cell and degree of keratinization in the foreskins of Chinese
      preschool boys and adults. METHODS: Sixty preschool boys and 20 healthy men
      without infectious history following male circumcisions were included. The
      keratin thickness and Langerhans' cells were quantified by using keratin
      staining, immunohistochemistry, and image analysis. RESULTS: The extent of
      keratinization was much greater in the inner foreskin than in the outer foreskin
      in adults and boys with infectious history. It was likely to be less keratinized
      in boys' foreskins compared with those of adults. The density of Langerhans'
      cells was higher in the outer foreskin than in the inner foreskin of adults and
      healthy boys. Furthermore, an increased density of Langerhans' cells of inner
      foreskin was also found in boys with infectious history compared with healthy
      boys. There was much higher Langerhans' cell density in boys' foreskin compared
      with those of adults. CONCLUSIONS: These findings suggest that Chinese men may
      have a different feature of keratin in the foreskin, and a higher Langerhans'
      cells density in boys' foreskin may be due to it being less keratinized.

PMID- 19184516
TI  - Quasi steady state growth of Lactococcus lactis in glucose-limited acceleration
      stat (A-stat) cultures.
AB  - Quasi steady state growth of Lactococcus lactis IL 1403 was studied in glucose
      limited A-stat cultivation experiments with acceleration rates (a) from 0.003 to
      0.06 h(-2) after initial stabilization of the cultures in chemostat at D = 0.2
      0.3 h(-1). It was shown that the high limit of quasi steady state growth rate
      depended on the acceleration rate used-at an acceleration rate 0.003 h(-2) the
      quasi steady state growth was observed until mu (crit) = 0.59 h(-1), which is
      also the mu (max) value for the culture. Lower values of mu (crit) were observed
      at higher acceleration rates. The steady state growth of bacteria stabilized at
      dilution rate 0.2 h(-1) was immediately disrupted after initiating acceleration
      at the highest acceleration rate studied-0.06 h(-2). Observation was made that
      differences [Delta(mu - D)] of the specific growth rates from pre-programmed
      dilution rates were the lowest using an acceleration rate of 0.003 h(-2) (< 4% of
      preset changing growth rate). The adaptability of cells to follow preprogrammed
      growth rate was found to decrease with increasing dilution rate-it was shown that
      lower acceleration rates should be applied at higher growth rates to maintain the
      culture in the quasi steady state. The critical specific growth rate and the
      biomass yields based on glucose consumption were higher if the medium contained S
      (0) = 5 g L(-1) glucose instead of S (0) = 10 g L(-1). It was assumed that this
      was due to the inhibitory effect of lactate accumulating at higher concentrations
      in the latter cultures. Parallel A-stat experiments at the same acceleration and
      dilution rates showed good reproducibility-Delta(mu - D) was less than 5%,
      standard deviations of biomass yields per ATP produced (Y (ATP)), and biomass
      yields per glucose consumed (Y (XS)) were less than 15%.

PMID- 19184515
TI  - The metabolic etiology of urolithiasis in Turkish children.
AB  - Pediatric urolithiasis is an endemic disease, especially in certain developing
      regions of the world, such as the Far East, and to a certain extent the Middle
      East and Turkey. The aim of the study is to determine the metabolic etiology and
      the prevalence of formation of urinary calculi in Turkish pediatric patients with
      urolithiasis. Seventy-two pediatric patients diagnosed as having urolithiasis
      were studied from 1999-2005 in Dr. Behcet Uz Child Disease and Surgery Education
      and Research Hospital Nephrology Department, Izmir, according to their presenting
      signs and clinical and laboratory findings. The other necessary tests were also
      applied to detect the etiology of the calculi formation. Of the 72 patients, 50
      (69.4%) were male and 22 (30.6%) were female, with ages ranging from 2 to 168
      months (mean age 72 +/- 35.7 months), and the male-to-female ratio of patients
      was 2.3. Twenty-four (33%) of them were diagnosed as having metabolic
      urolithiasis, 21 (30%) anatomic, 19 (26%) infectious and 8 (11%) idiopathic. The
      age at which urolithiasis was first diagnosed was found to be low in the
      metabolic and anatomic etiology groups (P = 0.028). Thirteen patients (18%) with
      urolithiasis were known to have a family history of stone disease, and in all of
      them metabolic etiology was considered to be the reason (P < 0.001). In all of
      the groups, the localization of the stone was found to be the upper urinary
      system most of the time, and in 17 (24%) with bilateral multiple stones, the
      etiology was found to be metabolic (P < 0.001). All of the patients were followed
      up for 3-72 months (mean 29.2 +/- 13.7 months), and four of them (5.5%) had
      recurrences. In order to prevent renal damage and recurrences in pediatric
      patients with urolithiasis in Turkey in whom the etiology is mostly metabolic,
      the illnesses must be investigated very cautiously, and their early diagnosis and
      treatment modalities must be considered.

PMID- 19184517
TI  - Resident physician and hospital pharmacist familiarity with patient discharge
      medication costs.
AB  - OBJECTIVE: Cost-related medication non-adherence is associated with increased
      health-care resource utilization and poor patient outcomes. Physicians-in
      training generally receive little education regarding costs of prescribed therapy
      and may rely on hospital pharmacists for this information. However, little is
      documented regarding either of these health care providers' familiarity with out
      of pocket medication expenses borne by patients in the community. The purpose of
      this study was to evaluate and compare resident physician and hospital pharmacist
      familiarity with what patients pay for medications prescribed once discharged.
      Setting A major tertiary patient care and medical teaching centre in Canada.
      METHOD: Internal medicine residents and hospital pharmacists within a specific
      health care organization were invited to participate in an online survey. Eight
      patient case scenarios and associated discharge therapeutic regimens were
      outlined and respondents asked to identify the costs patients would incur when
      having the prescription filled once discharged. MAIN OUTCOME MEASURE: Total
      number and proportion of estimates above and below actual cost were calculated
      and compared between the groups using chi(2) tests. Responses +/-10% of the true
      cost were considered correct. Mean absolute values and standard deviation
      estimated costs, as well as cost increments above and below 10%, were calculated
      to assess the magnitude of the discrepancy between the respondent estimates and
      the actual total cost. RESULTS: Forty-four percent of physician residents and 26%
      of hospital pharmacists accessed the survey. Overall 39% and 47% of medication
      costs were under-estimated, 32% and 33% were overestimated, and 29% and 21% were
      correctly estimated by residents and pharmacists, respectively (P = NS).
      Incorrect estimates were evident across all therapeutic classes and medical
      indications presented in the survey. The greatest absolute cost discrepancy for
      both groups was under-estimation of linezolid ($800 and $400) and over-estimation
      of clopidogrel ($80) and bisoprolol therapy ($22) by residents and pharmacists,
      respectively. CONCLUSION; Resident physicians and hospital pharmacists are
      unfamiliar with what patients must pay for drug therapy once discharged.

PMID- 19184520
TI  - Abstracts from the 8th European Workshop on Astrobiology, Neuchatel, Switzerland,
      1-3 September, 2008.

PMID- 19184518
TI  - Electron-nuclear double resonance.
AB  - The application of electron-nuclear double resonance (ENDOR) spectroscopy for the
      investigation of photosynthetic systems is reviewed. The basic principles of
      continuous wave and pulse ENDOR are presented. Selected examples of the
      application of the ENDOR technique for studying stable and transient paramagnetic
      species, including cofactor radical ions, radical pairs, triplet states, and the
      oxygen-evolving complex in plant Photosystem II (PSII) are discussed. Limitations
      and perspectives of ENDOR spectroscopy are outlined.

PMID- 19184521
TI  - Right and left atrial appendage function in patients with mitral stenosis and
      sinus rhythm.
AB  - Tissue Doppler imaging (TDI) is generally used for the assessment of ventricular
      function, and to a lesser extent, to evaluate the left atrial appendage (LAA). In
      the present study, we used TDI to analyze the contractile function of the right
      atrial appendage (RAA). The aim of this study was a comprehensive evaluation of
      RAA and LAA contractile function in patients with mitral stenosis and sinus
      rhythm. A total of 69 patients were assessed: group 1 (23 patients with severe
      MS, 38 +/- 11 years, 20 women), group 2 (23 patients with mild MS, 39 +/- 12
      years, 19 women) and group 3 (23 healthy subjects, 42 +/- 14 years, 16 women).
      Multiplane transesophageal echo was performed in all patients. The RAA was
      visualized at 130 degrees and the LAA at 0 degrees . TDI sample volume was placed
      in the tip of both atrial appendages, with an ultrasound beam angle < 10 degrees
      . Flow velocities and myocardial velocities were measured. The presence of
      thrombus and/or spontaneous echo contrast (SEC) was assessed. TDI showed in
      normal subjects, myocardial contraction velocities in RAA similar to that of the
      LAA (21.8 +/- 4.2 vs. 20.1 +/- 4 cm/s, respectively, P = NS). In patients with
      MS, myocardial velocities in both atrial appendages were significantly lower than
      in normal subjects (RAA: 17.4 +/- 5.1 vs. 21.8 +/- 4.2 cm/s, respectively, P <
      0.01, LAA: 9 +/- 5.1 vs. 20.1 +/- 4 cm/s, respectively, P < 0.001). Linear
      regression analysis showed a correlation between the impairment of systolic
      function of both appendages, pulmonary arterial pressure, valve area and
      transmitral gradient. Of the 46 patients with MS, patients with intense SEC had
      lower flow and myocardial velocities in the LAA than patients without SEC (16 +/-
      5 vs. 50 +/- 3 cm/s, 6 +/- 2 vs. 10.6 +/- 5.6 cm/s, respectively, P < 0.001 and P
      < 0.001). In healthy subjects, myocardial contraction velocities in both
      appendages were similar. Patients with MS and sinus rhythm had contractile
      dysfunction of both appendages, shown by the decrease in myocardial velocities
      and related to the increase in atrial afterload. Both appendages exhibited a
      relation between contractile dysfunction and the presence of SEC, but dysfunction
      was less marked in the RAA, which might explain the lower prevalence of thrombi
      in the RAA.

PMID- 19184523
TI  - Investigation of T2-weighted signal intensity of infarcted myocardium and its
      correlation with delayed enhancement magnetic resonance imaging in a porcine
      model with reperfused acute myocardial infarction.
AB  - To assess the signal pattern in T2-weighted images (T2WI) and determine its
      relation to persistent microvascular obstruction (PMO) and intramyocardial
      hemorrhage in a porcine model with reperfused acute myocardial infarction. Left
      anterior descending artery was occluded (90 or 180 min) and reperfused (90 min).
      T2WI and delayed-enhanced magnetic resonance images (DE-MRI) were acquired. The
      T2WI signal pattern, T2WI contrast ratio, PMO, and intramyocardial hemorrhage
      were evaluated, and their interrelationships were analyzed. The infarct area on
      T2WI was recorded as a homogeneous high-intensity signal or as low- or iso
      intensity signals. The contrast ratio of the T2WI in the cases with PMO was
      significantly lower than that in those without PMO (1.38 +/- 0.25 vs. 1.89 +/-
      0.31, P < 0.05), and it showed significant inverse correlation with the extent of
      PMO observed in DE-MRI images (r =-0.8, P < 0.05). The extent of PMO correlated
      strongly with that of intramyocardial hemorrhage (r = 0.97, P < 0.05). The
      abnormal signal area in the T2WI was larger than the infarct area in the DE-MRI
      images (47.0 +/- 9.9% vs. 37.8 +/- 9.9%, P < 0.05) and the infarct area observed
      after TTC staining (47.0 +/- 9.9% vs. 37.4 +/- 8.4%, P < 0.05). We observed
      variable T2WI signal patterns for the infarcted myocardium. Lower T2WI contrast
      ratios significantly correlated with the extent of PMO in DE-MRI and
      intramyocardial hemorrhage in the gross specimen.